PMID- 25559343
TI  - Structure-inherent targeting of near-infrared fluorophores for parathyroid and
      thyroid gland imaging.
AB  - The typical method for creating targeted contrast agents requires covalent
      conjugation of separate targeting and fluorophore domains. In this study, we
      demonstrate that it is possible to create near-infrared (NIR) fluorophores with
      different tissue specificities driven by their inherent chemical structures.
      Thus, a single compact molecule performs both targeting and imaging. We use this
      strategy to solve a major problem in head and neck surgery: the identification
      and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800
      nm halogenated fluorophores that show high uptake into these glands after a
      single intravenous (IV) injection of 0.06 mg kg(-1) in a pig. By using a dual
      channel NIR imaging system, we observed-in real time and with high sensitivity
      the unambiguous distinction of parathyroid and thyroid glands simultaneously in
      the context of blood and surrounding soft tissue. This novel technology lays a
      foundation for performing head and neck surgery with increased precision and
      efficiency along with potentially lower morbidity, and it provides a general
      strategy for developing targeted NIR fluorophores. 

PMID- 25559345
TI  - Multi-MitraClip therapy for severe degenerative mitral regurgitation: "anchor"
      technique for extremely flail segments.
AB  - In high-risk or inoperable patients, implantation of MitraClip for treatment of
      severe symptomatic mitral regurgitation (MR) from central (A2/P2 pathology,
      EVEREST patient) is effective in reducing symptoms and improving functional
      class. Extending the use of MitraClip to the non-EVEREST patient is of
      considerable interest. MitraClip implantation for wide flail segments and non
      central MR is technically more challenging but represents an important and highly
      prevalent subset of patients. We present a case of an 82-year-old male referred
      to our institution for medically refractory primary MR. Trans-esophageal
      echocardiogram demonstrated severe (4+) MR, annular dilatation, P3 > P2 mitral
      valve prolapse, malcoaptation, and wide flail gaps and widths. The patient's age,
      frailty, chronic kidney disease, and mild cognitive impairment rendered him a
      candidate for MitraClip therapy. Our target area, the areas of maximum flail
      (A3/P3), proved too wide for grasping. Hence, the first clip was deployed medial
      to the target area. Subsequent deployment, in a sequential fashion ("zipper
      technique"), was not technically feasible due to persistent instability of the
      target area. Consideration was given to an alternative approach by "anchoring"
      our target area where the 2nd and 3rd clips were deployed lateral to the A3/P3
      segment in efforts to "anchor" the maximum flail segment. This maneuver allowed
      final clip deployment into a more stable target area. Subsequent imaging
      demonstrated reduction in MR from 4+ to 1+ with preservation of a normal
      transmitral gradient. We report the first successful US case of four MitraClip
      implantation for the treatment of severe primary MR by "anchoring" flail
      segments.

PMID- 25559346
TI  - A population-based longitudinal study of recent stressful life events as risk
      factors for suicidal behavior in major depressive disorder.
AB  - The purpose of this study is to investigate whether the type and number of
      stressful life events (SLEs) will be associated with suicidal behavior in a 3
      year follow-up period in persons with major depressive disorder (MDD). Data came
      from the National Epidemiologic Survey on Alcohol and Related Conditions
      (NESARC), a nationally representative longitudinal survey of mental health in non
      institutionalized adults in the United States. The survey consisted of two waves:
      Wave 1 (2001--2002) and Wave 2 (2004-2005), n = 34,653. Twelve past-year SLEs
      were assessed at baseline. These SLEs were categorized into the following groups
      based on previous research: Loss or victimization; Relationship, friendship, or
      interpersonal stress; Financial stress; and Legal problems. Only respondents with
      MDD at Wave 1 were included (n = 6,004). Several SLEs were strongly associated
      with suicide attempts, among which, "serious problems with neighbor, friend, or
      relative" (adjusted odds ratio [AOR] = 2.21; 95% confidence interval [95% CI]:
      1.41, 3.45) and "major financial crisis, bankruptcy, or unable to pay bills" (AOR
      = 2.31; 95% CI: 1.45, 3.66) were the most robust predictors of suicide attempts
      even after adjusting for sociodemographic variables and any anxiety, substance
      use, or personality disorder. People with MDD who had been exposed to certain
      SLEs are at elevated risk for future suicide attempts, even after accounting for
      the demographic factors and psychiatric comorbidity.

PMID- 25559344
TI  - Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and
      insulin resistance.
AB  - The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR)
      has led to promising new therapies targeting cholesterol metabolism, triglyceride
      production, hepatic steatosis and biliary cholestasis. In contrast to systemic
      therapy, bile acid release during a meal selectively activates intestinal FXR. By
      mimicking this tissue-selective effect, the gut-restricted FXR agonist fexaramine
      (Fex) robustly induces enteric fibroblast growth factor 15 (FGF15), leading to
      alterations in BA composition, but does so without activating FXR target genes in
      the liver. However, unlike systemic agonism, we find that Fex reduces diet
      induced weight gain, body-wide inflammation and hepatic glucose production, while
      enhancing thermogenesis and browning of white adipose tissue (WAT). These
      pronounced metabolic improvements suggest tissue-restricted FXR activation as a
      new approach in the treatment of obesity and metabolic syndrome. 

PMID- 25559348
TI  - Dual-effect liposomes encapsulated with doxorubicin and chlorin e6 augment the
      therapeutic effect of tumor treatment.
AB  - BACKGROUND AND OBJECTIVE: Long circulating doxorubicin (Dox)-loaded PEGylated
      liposomes are clinically safer than the free form due to the significant
      reduction of cardiac toxicity. However, the therapeutic efficacy of the PEGylated
      liposome could further be improved if poor diffusivity and slow drug release of
      the liposome in tumor interstitium can be overcome. In this study, a dual-effect
      liposome triggered by photodynamic effect was developed to improve the
      therapeutic efficacy of Dox-loaded PEGylated liposomes. MATERIALS AND METHODS:
      Dox and chlorin e6 (Ce6) were co-encapsulated in PEGylated liposomes (named as PL
      Dox-Ce6). To induce the drug release, photodynamic effect was triggered by the
      light irradiation of a 662 nm diode laser. The cellular distribution of Dox and
      Ce6 was examined under confocal microscope. The in vitro and in vivo cytotoxicity
      of PL-Dox-Ce6 was determined via the colony formation assay and the synergistic
      C26 tumor model, respectively. RESULTS: The cellular distribution of PL-Dox-Ce6
      was in the cytoplasmic area; while under light irradiation, Dox was co-localized
      with nuclear staining positive signals. The cellular cytotoxicity of PL-Dox-Ce6
      was significantly higher than the controls including liposomes encapsulating
      either Dox (PL-Dox) or Ce6 (PL-Ce6). The in vivo treatment efficacy of PL-Dox-Ce6
      determined in the C26 tumor model reveals a significant therapeutic effect
      compared to that of PL-Ce6 and PL-Dox alone or in combination. CONCLUSION: This
      study indicates that this dual-effect PEGylated liposome could provide clinical
      advantages in the combination regimen of photodynamic therapy and chemotherapy.

PMID- 25559347
TI  - Design, synthesis, and biological evaluation of tetrazole analogs of Cl-amidine
      as protein arginine deiminase inhibitors.
AB  - Protein arginine deiminases (PADs) catalyze the post-translational hydrolysis of
      arginine residues to form citrulline. This once obscure modification is now known
      to play a key role in the etiology of multiple autoimmune diseases (e.g.,
      rheumatoid arthritis, multiple sclerosis, lupus, and ulcerative colitis) and in
      some forms of cancer. Among the five human PADs (PAD1, -2, -3, -4, and -6), it is
      unclear which isozyme contributes to disease pathogenesis. Toward the
      identification of potent, selective, and bioavailable PAD inhibitors that can be
      used to elucidate the specific roles of each isozyme, we describe tetrazole
      analogs as suitable backbone amide bond bioisosteres for the parent pan PAD
      inhibitor Cl-amidine. These tetrazole based analogs are highly potent and show
      selectivity toward particular isozymes. Importantly, one of the compounds,
      biphenyl tetrazole tert-butyl Cl-amidine (compound 13), exhibits enhanced cell
      killing in a PAD4 expressing osteosarcoma bone marrow (U2OS) cell line and can
      also block the formation of neutrophil extracellular traps. These bioisosteres
      represent an important step in our efforts to develop stable, bioavailable, and
      selective inhibitors for the PADs. 

PMID- 25559349
TI  - Development of a functional cell-based assay that probes the specific interaction
      between influenza A virus NP and its packaging signal sequence RNA.
AB  - Although cis-acting packaging signal RNA sequences for the influenza virus NP
      encoding vRNA have been identified recently though genetic studies, little is
      known about the interaction between NP and the vRNA packaging signals either in
      vivo or in vitro. Here, we provide evidence that NP is able to interact
      specifically with the vRNA packaging sequence RNA within living cells and that
      the specific RNA binding activity of NP in vivo requires both the N-terminal and
      central region of the protein. This assay established would be a valuable tool
      for further detailed studies of the NP-packaging signal RNA interaction in living
      cells. 

PMID- 25559350
TI  - Target-specific oral anticoagulants and the hospitalist.
AB  - As a class, the target-specific oral anticoagulants (TSOACs) are at least as
      effective as warfarin, often with superior safety for the prevention of stroke in
      patients with nonvalvular atrial fibrillation (AF) and the treatment of acute
      venous thromboembolism (VTE) and prevention of recurrent VTE. Currently,
      dabigatran, the direct thrombin inhibitor, along with rivaroxaban and apixaban,
      direct factor Xa inhibitors, has been approved in multiple countries for these
      indications. Edoxaban, which has received approval for the abovementioned
      indications in Japan, has demonstrated efficacy and safety comparable to or
      better than warfarin in Phase III clinical trials and is under further regulatory
      consideration. It is anticipated that the use of TSOACs will increase as
      practitioners and healthcare systems gain familiarity with these drugs and adopt
      their use into clinical practice. This review will provide a brief overview of
      the TSOAC Phase III clinical trials for prevention of stroke and systemic embolic
      events in patients with AF and the Phase III clinical trials for the prevention
      of recurrent VTE, discuss current treatment guidelines, address how TSOACs may
      help meet national safety goals, and provide clinical decision-making guidance
      regarding the use of TSOACs for hospitalists.

PMID- 25559351
TI  - Effects of short-term manipulation of serum FFA concentrations on left
      ventricular energy metabolism and function in patients with heart failure: no
      association with circulating bio-markers of inflammation.
AB  - BACKGROUND AND AIMS: We wanted to assess the effects of short-term changes in
      serum free fatty acids (FFAs) on left ventricular (LV) energy metabolism and
      function in patients with heart failure and whether they correlated with
      circulating markers of inflammation. METHODS AND RESULTS: LV function and
      phosphocreatine (PCr)/ATP ratio were assessed using MR imaging (MRI) and 31P
      magnetic resonance spectroscopy (MRS) in 11 men with chronic heart failure in two
      experimental conditions 7 days apart. Study 1: MRI and 31P-MRS were performed
      before and 3-4 h after i.v. bolus + continuous heparin infusion titrated to
      achieve a serum FFA concentration of 1.20 mM. Study 2: The same protocol was
      performed before and after the oral administration of acipimox titrated to
      achieve a serum FFA concentration of 0.20 mM. Serum concentrations of IL6, TNF
      alpha, PAI-1, resistin, visfatin and leptin were simultaneously assessed. Serum
      glucose and insulin concentrations were not different between studies. The
      PCr/ATP ratio (percent change from baseline: +6.0 +/- 16.9 and -16.6 +/- 16.1 %
      in Study 1 and Study 2, respectively; p = 0.005) and the LV ejection fraction (
      1.5 +/- 4.0 and -6.9 +/- 6.3 % in Study 1 and Study 2, respectively; p = 0.044)
      were reduced during low FFA when compared to high FFA. Serum resistin was higher
      during Study 1 than in Study 2 (p < 0.05 repeated measures ANOVA); meanwhile, the
      other adipocytokines were not different. CONCLUSION: FFA deprivation, but not
      excess, impaired LV energy metabolism and function within hours. Cautions should
      be used when sudden iatrogenic modulation of energy substrates may take place in
      vulnerable patients.

PMID- 25559352
TI  - Ethnic/racial determinants of glycemic markers in a UK sample.
AB  - OBJECTIVE: To investigate possible causes for previously reported glycemia
      independent South Asian-white differences in HbA1c. METHODS: Demographic and
      laboratory data on non-diabetic patients from primary care were analyzed. Linear
      regression models measured the association between race/ethnicity and three
      glycemic measures (HbA1c, fructosamine and fasting plasma glucose), adjusted for
      a range of hematological, biochemical and demographic factors. RESULTS: Nine
      hundred and forty-eight patients consisting of 711 white subjects (407 women) and
      237 South Asian subjects (138 women) were studied. Unadjusted bivariate analysis
      showed that South Asians had higher HbA1c concentrations [41 (5.9 %) vs. 40 (5.8
      %) mmol/mol (p = 0.011), coefficient 1.21, 95 % CI 0.27, 2.17 (p = 0.011)]
      similar fructosamine [228.4 vs. 226.7 mmol/L (p = 0.352), coefficient 3.93, 95 %
      CI 0.79, 7.08 (p = 0.014)] and fasting plasma glucose [5.1 vs. 5.2 mmol/L (p =
      0.154), coefficient -0.09, 95 % CI -0.22, -0.04 (p = 0.156)] concentrations than
      whites. South Asians also had lower hemoglobin, ferritin and vitamin B12
      concentrations than whites. After adjustment for independent variables, South
      Asian ethnicity was associated with higher HbA1c concentrations [0.89, 95 % CI
      0.06-1.72 (p = 0.035)], higher fructosamine levels [3.93, 95 % CI 0.79, 7.08 (p =
      0.014)] and lower fasting plasma glucose concentrations [-0.12, 95 % CI -0.26, 
      0.02 (p = 0.026)] compared to white race. CONCLUSIONS: The increased prevalence
      of hematological abnormalities in South Asians and their higher adjusted HbA1c
      and fructosamine but lower fasting glucose levels compared to white subjects
      suggest that ethnic differences in glycation markers may, in part, be due to a
      combination of erythrocyte factors and glycemia-independent glycation.

PMID- 25559353
TI  - What measures of habit strength to use? Comment on Gardner (2015).

PMID- 25559354
TI  - Identification of genes and pathways involved in kidney renal clear cell
      carcinoma.
AB  - BACKGROUND: Kidney Renal Clear Cell Carcinoma (KIRC) is one of fatal
      genitourinary diseases and accounts for most malignant kidney tumours. KIRC has
      been shown resistance to radiotherapy and chemotherapy. Like many types of
      cancers, there is no curative treatment for metastatic KIRC. Using advanced
      sequencing technologies, The Cancer Genome Atlas (TCGA) project of NIH/NCI-NHGRI
      has produced large-scale sequencing data, which provide unprecedented
      opportunities to reveal new molecular mechanisms of cancer. We combined
      differentially expressed genes, pathways and network analyses to gain new
      insights into the underlying molecular mechanisms of the disease development.
      RESULTS: Followed by the experimental design for obtaining significant genes and
      pathways, comprehensive analysis of 537 KIRC patients' sequencing data provided
      by TCGA was performed. Differentially expressed genes were obtained from the RNA
      Seq data. Pathway and network analyses were performed. We identified 186
      differentially expressed genes with significant p-value and large fold changes (P
      < 0.01, |log(FC)| > 5). The study not only confirmed a number of identified
      differentially expressed genes in literature reports, but also provided new
      findings. We performed hierarchical clustering analysis utilizing the whole
      genome-wide gene expressions and differentially expressed genes that were
      identified in this study. We revealed distinct groups of differentially expressed
      genes that can aid to the identification of subtypes of the cancer. The
      hierarchical clustering analysis based on gene expression profile and
      differentially expressed genes suggested four subtypes of the cancer. We found
      enriched distinct Gene Ontology (GO) terms associated with these groups of genes.
      Based on these findings, we built a support vector machine based supervised
      learning classifier to predict unknown samples, and the classifier achieved high
      accuracy and robust classification results. In addition, we identified a number
      of pathways (P < 0.04) that were significantly influenced by the disease. We
      found that some of the identified pathways have been implicated in cancers from
      literatures, while others have not been reported in the cancer before. The
      network analysis leads to the identification of significantly disrupted pathways
      and associated genes involved in the disease development. Furthermore, this study
      can provide a viable alternative in identifying effective drug targets.
      CONCLUSIONS: Our study identified a set of differentially expressed genes and
      pathways in kidney renal clear cell carcinoma, and represents a comprehensive
      computational approach to analysis large-scale next-generation sequencing data.
      The pathway and network analyses suggested that information from distinctly
      expressed genes can be utilized in the identification of aberrant upstream
      regulators. Identification of distinctly expressed genes and altered pathways are
      important in effective biomarker identification for early cancer diagnosis and
      treatment planning. Combining differentially expressed genes with pathway and
      network analyses using intelligent computational approaches provide an
      unprecedented opportunity to identify upstream disease causal genes and effective
      drug targets.

PMID- 25559356
TI  - One-step electrodeposition process to fabricate corrosion-resistant
      superhydrophobic surface on magnesium alloy.
AB  - A simple, one-step method has been developed to construct a superhydrophobic
      surface by electrodepositing Mg-Mn-Ce magnesium plate in an ethanol solution
      containing cerium nitrate hexahydrate and myristic acid. Scanning electron
      microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron
      spectroscopy, and Fourier transform infrared spectroscopy were employed to
      characterize the surfaces. The shortest electrodeposition time to obtain a
      superhydrophobic surface was about 1 min, and the as-prepared superhydrophobic
      surfaces had a maximum contact angle of 159.8 degrees  and a sliding angle of
      less than 2 degrees . Potentiodynamic polarization and electrochemical impedance
      spectroscopy measurements demonstrated that the superhydrophobic surface greatly
      improved the corrosion properties of magnesium alloy in 3.5 wt % aqueous
      solutions of NaCl, Na2SO4, NaClO3, and NaNO3. Besides, the chemical stability and
      mechanical durability of the as-prepared superhydrophobic surface were also
      examined. The presented method is rapid, low-cost, and environmentally friendly
      and thus should be of significant value for the industrial fabrication of
      anticorrosive superhydrophobic surfaces and should have a promising future in
      expanding the applications of magnesium alloys. 

PMID- 25559355
TI  - Fasting gut hormone levels change with modest weight loss in obese adolescents.
AB  - BACKGROUND: Gut hormones change with weight loss in adults but are not well
      studied in obese youth. OBJECTIVE: The primary aim was to evaluate how gut
      hormones and subjective appetite measure change with dietary weight loss in obese
      adolescents. METHODS: Participants were a subset of those taking part in the 'Eat
      Smart Study'. They were aged 10-17 years with body mass index (BMI) > 90th
      centile and were randomized to one of three groups: wait-listed control,
      structured reduced carbohydrate or structured low-fat dietary intervention for 12
      weeks. Outcomes were fasting glucose, insulin, leptin, adiponectin, total amylin,
      acylated ghrelin, active glucagon-like peptide-1, glucose-dependent
      insulinotropic polypeptide (GIP), pancreatic polypeptide (PP) and total peptide
      tyrosine-tyrosine. Pre- and postprandial subjective sensations of appetite were
      assessed using visual analogue scales. RESULTS: Of 87 'Eat Smart' participants,
      74 participated in this sub-study. The mean (standard deviation) BMI z-score was
      2.1 (0.4) in the intervention groups at week 12 compared with 2.2 (0.4) in the
      control group. Fasting insulin (P = 0.05) and leptin (P = 0.03) levels decreased,
      while adiponectin levels increased (P = 0.05) in the intervention groups compared
      with control. The intervention groups were not significantly different from each
      other. A decrease in BMI z-score at week 12 was associated with decreased fasting
      insulin (P < 0.001), homeostatic model of assessment-insulin resistance (P <
      0.001), leptin (P < 0.001), total amylin (P = 0.03), GIP (P = 0.01), PP (P =
      0.02) and increased adiponectin (P < 0.001). There was no significant difference
      in appetite sensations. CONCLUSIONS: Modest weight loss in obese adolescents
      leads to changes in some adipokines and gut hormones that may favour weight
      regain.

PMID- 25559357
TI  - Risk factors for poor neonatal adaptation after exposure to antidepressants in
      utero.
AB  - AIM: Infants exposed to antidepressants in utero are at risk of developing poor
      neonatal adaptation (PNA). This study identified risk factors for PNA. METHODS:
      In this cohort study, data on mothers and infants admitted to the maternity ward
      of a general hospital between 2007 and 2012 were analysed. All infants were
      exposed to an antidepressant during the last trimester of foetal life. The main
      outcome measure was PNA, defined as at least one Finnegan scores of four or more
      during admission. Risk factors analysed for their possible association with PNA
      included type of feeding, type and dosage of antidepressant, prematurity and
      maternal smoking, anxiety and depression. RESULTS: We included 247 infants in the
      study and 157 (64%) developed PNA. Formula feeding was associated with an
      increased risk of PNA compared to breastfeeding or mixed feeding (OR 3.16 95% CI
      1.40-7.13 p = 0.003). Selective serotonin reuptake inhibitors (SSRIs) were
      associated with an increased risk of PNA compared to serotonin and noradrenaline
      reuptake inhibitors (OR 2.52 95% CI 1.07-5.95 p = 0.04). Dosage did not influence
      the risk of PNA (OR 1.50 95% CI 0.89-2.52 p = 0.13). CONCLUSION: Formula feeding
      and exposure to SSRIs were associated with development of PNA, but dosage was
      not.

PMID- 25559358
TI  - Association between serum C-peptide as a risk factor for cardiovascular disease
      and high-density lipoprotein cholesterol levels in nondiabetic individuals.
AB  - OBJECTIVE: Objective: Although serum C-peptide has increasingly received
      attention as a new and important risk factor for cardiovascular disease (CVD),
      the potential mechanisms remain unclear. This study aimed to investigate the
      association between serum C-peptide as a risk factor for CVD and high-density
      lipoprotein cholesterol (HDL-C) levels. METHODS: The present study included
      13,185 participants aged >=20 years. Serum C-peptide and HDL-C levels were
      measured according to a standard protocol. Stratified analysis of covariance was
      used to compare serum HDL-C levels between different quartiles of serum C-peptide
      levels. Logistic regression analysis was used to determine the association
      between serum C-peptide and HDL-C levels. Cox proportional hazard regression
      analysis was conducted to determine the hazard ratio of serum HDL-C for CVD
      related mortality. RESULTS: The results of the ANCOVA analysis showed a
      significant linear trend between the mean serum HDL-C level and the different
      quartiles of serum C-peptide. Compared to the first quartile (25th percentile),
      the second, third, and fourth quartiles had gradual reduction in serum HDL-C
      levels. Logistic regression analyses showed a strong negative association between
      serum C-peptide levels and HDL-C levels; the p value for the linear trend was
      <0.001. In men, compared with the lowest quartile of the serum C-peptide level,
      the relative risk was 1.75, 2.79, and 3.07 for the upper three quartiles of the
      serum C-peptide level. The relative risk was 1.60, 2.61, and 3.67 for women. The
      results of the survival analysis showed that serum HDL-C levels were negatively
      associated with CVD-related death in both men and women. CONCLUSION: Serum C
      peptide as a risk factor for CVD was significantly and negatively associated with
      serum HDL-C levels in individuals without diabetes. These findings suggest that
      serum C-peptide levels association with CVD death can be caused, at least in
      part, by the low serum HDL-C level.

PMID- 25559359
TI  - Caveolin-1 mediates inflammatory breast cancer cell invasion via the Akt1 pathway
      and RhoC GTPase.
AB  - With a propensity to invade the dermal lymphatic vessels of the skin overlying
      the breast and readily metastasize, inflammatory breast cancer (IBC) is arguably
      the deadliest form of breast cancer. We previously reported that caveolin-1 is
      overexpressed in IBC and that RhoC GTPase is a metastatic switch responsible for
      the invasive phenotype. RhoC-driven invasion requires phosphorylation by Akt1.
      Using a reliable IBC cell line we set out to determine if caveolin-1 expression
      affects RhoC-mediated IBC invasion. Caveolin-1 was down regulated by introduction
      of siRNA or a caveolin scaffolding domain. The ability of the cells to invade was
      tested and the status of Akt1 and RhoC GTPase examined. IBC cell invasion is
      significantly decreased when caveolin-1 is down regulated. Activation of Akt1 is
      decreased when caveolin-1 is down regulated, leading to decreased phosphorylation
      of RhoC GTPase. Thus, we report here that caveolin-1 overexpression mediates IBC
      cell invasion through activation Akt1, which phosphorylates RhoC GTPase.

PMID- 25559360
TI  - Porous C3N4 nanolayers@N-graphene films as catalyst electrodes for highly
      efficient hydrogen evolution.
AB  - Pt-free electrocatalysts for hydrogen evolution reaction (HER) with high activity
      and low price are desirable for many state-of-the-art renewable energy devices,
      such as water electrolysis and photoelectrochemical water splitting cells.
      However, the design and fabrication of such materials remain a significant
      challenge. This work reports the preparation of a flexible three-dimensional (3D)
      film by integrating porous C3N4 nanolayers with nitrogen-doped graphene sheets,
      which can be directly utilized as HER catalyst electrodes without substrates.
      This nonmetal electrocatalyst has displayed an unbeatable HER performance with a
      very positive onset-potential close to that of commercial Pt (8 mV vs 0 mV of
      Pt/C, vs RHE @ 0.5 mA cm(-2)), high exchange current density of 0.43 mA cm(-2),
      and remarkable durability (seldom activity loss >5000 cycles). The extraordinary
      HER performance stems from strong synergistic effect originating from (i) highly
      exposed active sites generated by introduction of in-plane pores into C3N4 and
      exfoliation of C3N4 into nanosheets, (ii) hierarchical porous structure of the
      hybrid film, and (iii) 3D conductive graphene network. 

PMID- 25559361
TI  - NK22 Cells in the Uterine Mid-Secretory Endometrium and Peripheral Blood of Women
      with Recurrent Pregnancy Loss and Unexplained Infertility.
AB  - PROBLEM: We aimed to investigate natural killer 22 (NK22) cells in the peripheral
      blood and the uterine endometrium of women with unexplained recurrent pregnancy
      loss (URPL) and unexplained infertility (UI). METHOD OF STUDY: Peripheral blood
      and endometrial samples were collected from women with URPL (n = 43) and UI (n =
      38). Intracellular cytokine production, such as IL-22, IFN-gamma and TNF-alpha,
      and the expression of NKp46 on NK cells were analyzed by three-color flow
      cytometry. RESULTS: The percentages of endometrial CD56(+) /IL-22(+) and
      CD56(dim) /IL-22(+) cells in women with URPL were significantly higher than those
      of UI (P < 0.05, respectively). In addition, the percentage of CD56(bright) /IL
      22(+) cells in women with RPL was negatively correlated with those of
      CD56(bright) /IFN-gamma(+) and CD56(bright) /TNF-alpha(+) in both peripheral
      blood and endometrial NK cells. This was not seen in women with UI. The
      percentage of CD56(bright) /IL-22(+) cells was negatively correlated with
      CD56(bright) /NKp46 expressing NK cells in peripheral blood. CONCLUSION:
      Endometrial NK22 cells are differently regulated in women with URPL and UI. Women
      with URPL have higher level of NK22 cells with a potential to induce NK2 shift
      than women with UI.

PMID- 25559362
TI  - Barriers associated with the utilization of continued care among HIV-infected
      women who had previously enrolled in a private sector PMTCT program in
      Maharashtra, India.
AB  - Prevention of mother-to-child transmission (PMTCT) programs are considered as an
      entry point to continued care because they provide an opportunity to link an HIV
      infected woman, her partner, and child(ren) (if infected) to long-term treatment
      and care. However, little is known about the factors associated with the
      utilization of continued care among women who have previously accessed PMTCT
      services. Better knowledge of the barriers to continued care in HIV-infected
      women could lead to effective strategies to increase the uptake of post-PMTCT
      care. This study was designed to examine the factors associated with the
      utilization of continued care among HIV-infected women enrolled in the PRAYAS
      PMTCT program in Maharashtra, India, between 2002 and 2011. All consenting women
      who had completed the receipt of PMTCT services or who were lost to follow-up at
      least six months prior to the time of data collection were interviewed.
      Univariate and multivariate analyses were conducted to estimate the associations
      between not utilizing continued care and hypothesized risk factors using
      generalized linear models. Of the 688 eligible HIV-positive women, 311 completed
      a structured interview. Since their exit from the PMTCT program, 59 (19%) had
      never utilized HIV-related care, 58 (19%) had intermittently utilized HIV-related
      care, and 194 (62%) had consistently utilized HIV-related care at regular
      intervals. After adjusting for potential confounders, women with poor HIV-related
      knowledge (relative risk [RR] = 1.83; 95% CI: 1.15-2.92), women whose partners
      had never utilized HIV-related care (RR = 4.82; 95% CI: 2.57-9.04), and women who
      could not afford to travel to the HIV-care facility (RR = 2.36; 95% CI: 1.23
      4.53) were less likely to utilize HIV-related care after exiting the PMTCT
      program. This study highlights the need for enhanced techniques to impart HIV and
      antiretroviral therapy-related knowledge and underlines the need for improved
      partner involvement and financial support for travel to HIV facility to increase
      the uptake of post-PMTCT treatment and care. 

PMID- 25559364
TI  - [Bony avulsion of the extensor carpi radialis longus tendon from the base of the
      second metacarpal: A rare injury].
AB  - We report on a 19-year-old male patient with a rare injury: a basis fracture of
      the second metacarpal with avulsion of the extensor carpi radialis longus (ECRL)
      tendon. The patient was treated with open reduction and internal plate fixation
      of the fragment. The functional results after 10 months of follow-up were
      pronation/supination 90/0/90 degrees  (90/0/90 degrees ), extension/flexion
      70/0/70 degrees  (70/0/70 degrees ) radial/ulnar duction 20/0/40 degrees 
      (25/0/40 degrees ), bilateral grip strength was 115 kPa. The patient suffered no
      pain at all. The Mayo wrist score reached 100 points. Radiologically, the
      fracture was consolidated.Consistent diagnostics and surgical therapy lead to
      functional and radiological recovery following fracture of the second metacarpal
      base with avulsion of the extensor carpi radialis longus tendon.

PMID- 25559365
TI  - Civil disobedience, the energy-climate nexus and Australian coal exports.

PMID- 25559363
TI  - ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of
      prostate carcinoma cells.
AB  - Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading
      cause of male cancer death in Western nations. Thus, new treatment modalities are
      urgently needed. Elevated production of reactive oxygen species (ROS) by NADPH
      oxidase (Nox) enzymes is implicated in tumorigenesis of the prostate and other
      tissues. However, the identity of the Nox enzyme(s) involved in prostate
      carcinogenesis remains largely unknown. Analysis of radical prostatectomy tissue
      samples and benign and malignant prostate epithelial cell lines identified Nox5
      as an abundantly expressed Nox isoform. Consistently, immunohistochemical
      staining of a human PCa tissue microarray revealed distinct Nox5 expression in
      epithelial cells of benign and malignant prostatic glands. shRNA-mediated
      knockdown of Nox5 impaired proliferation of Nox5-expressing (PC-3, LNCaP) but not
      Nox5-negative (DU145) PCa cell lines. Similar effects were observed upon ROS
      ablation via the antioxidant N-acetylcysteine confirming ROS as the mediators. In
      addition, Nox5 silencing increased apoptosis of PC-3 cells. Concomitantly,
      protein kinase C zeta (PKCzeta) protein levels and c-Jun N-terminal kinase (JNK)
      phosphorylation were reduced. Moreover, the effect of Nox5 knockdown on PC-3 cell
      proliferation could be mimicked by pharmacological inhibition of JNK.
      Collectively, these data indicate that Nox5 is expressed at functionally relevant
      levels in the human prostate and clinical PCa. Moreover, findings herein suggest
      that Nox5-derived ROS and subsequent depletion of PKCzeta and JNK inactivation
      play a critical role in modulating intracellular signaling cascades involved in
      the proliferation and survival of PCa cells. (c) 2014 The Authors. Molecular
      Carcinogenesis published by Wiley Periodicals, Inc. 

PMID- 25559366
TI  - Relationship characteristics differ based on use of substances with sex among an
      urban internet sample of HIV-discordant and HIV-positive male couples.
AB  - Previous research with men who have sex with men (MSM) has found that substance
      use with sex is strongly associated with HIV acquisition and poor adherence to
      HIV treatments. Although some studies have assessed male couples' use of
      substances with unprotected anal sex, little is known on whether differences in
      their relationship dynamics are associated with their usage. Current HIV
      prevention initiatives underscore the importance of studying male couples'
      relationship dynamics. Using dyadic data from 28 HIV-positive and 58 HIV
      discordant male couples, this analysis sought to: (1) describe, by substance
      type, whether neither, one, or both partners in the couple used a particular
      substance with sex within their relationship or outside of the relationship,
      respectively, and (2) assess, by substance type, whether relationship
      characteristic differences existed between these three groups of couples with
      respect to substance use with sex within and outside the relationship. Data from
      86 dyads came from a cross-sectional, Internet study. Multivariate multinomial
      regression models were employed to achieve the aims. Except for alcohol, most did
      not use substances with sex. Within the relationship, those who used with sex
      varied by substance type; outside the relationship, most couples had only one
      partner who used with sex regardless of substance type. Several relationship
      characteristic differences were noted between the groups of couples. Within the
      relationship, marijuana and erectile dysfunction medication (EDM) use with sex
      was associated with having less tangible resources; for outside the relationship,
      these were associated with perceiving to have greater quality of alternatives. In
      general, amyl nitrates and party drug use with sex were associated with viewing
      the main partner as being less dependable for trustworthiness. Marijuana and
      party drug use with sex within the relationship and EDM use with sex outside the
      relationship were negatively associated with being able to communicate
      constructively. Mixed results were noted for relationship satisfaction.
      Additional research is urgently needed for prevention and promotion of healthy
      relationships for male couples who use substances with sex. 

PMID- 25559367
TI  - Role of indigenous iron in improving sludge dewaterability through peroxidation.
AB  - Improvement of sludge dewaterability is important for reducing the total costs
      for the treatment and disposal of sludge in wastewater treatment plants. In this
      study, we investigate the use of hydrogen peroxide as an oxidizing reagent for
      the conditioning of waste activated sludge. Significant improvement to sludge
      dewaterability was attained after the addition of hydrogen peroxide at 30 mg/g TS
      and 28 mg/g TS under acidic conditions (pH = 3.0), with the highest reduction of
      capillary suction time being 68% and 56%, respectively, for sludge containing an
      iron concentration of 56 mg Fe/g TS and 25 mg Fe/g TS, respectively. The
      observations were due to Fenton reactions between the iron contained in sludge
      (indigenous iron) and hydrogen peroxide. For the sludge with an insufficient
      level of indigenous iron, the addition of ferrous chloride was found to be able
      to improve the sludge dewaterability. The results firstly indicated that
      indigenous iron can be utilized similarly as the externally supplied iron salt to
      improve sludge dewaterability through catalyzing the Fenton reactions.

PMID- 25559368
TI  - Comment on "long-term (1930-2010) trends in groundwater levels in Texas:
      influences of soils, landcover, and water use" by Sriroop Chauduri and
      Srinivasulu Ale.

PMID- 25559369
TI  - Unabsorbed polylactide adhesion barrier mimicking recurrence of gynecologic
      malignant diseases with increased 18F-FDG uptake on PET/CT.
AB  - PURPOSE: To evaluate the incidence and characteristics of the unabsorbed
      polylactide adhesion barrier with increased (18)F-fluorodeoxyglucose ((18)F-FDG)
      uptake after surgeries for gynecologic malignancies. METHODS: Between September
      2006 and November 2009, we reviewed the charts of 75 patients who were provided a
      polylactide adhesion barrier after surgery for gynecologic malignant diseases. We
      surveyed the cases of increased (18)F-FDG uptake on positron emission
      tomography/computed tomography (PET/CT), and evaluated the effectiveness of
      polylactide adhesion barrier using an adhesion scoring system. RESULTS: Ten
      patients (13.3 %) had a solitary pelvic mass with increased (18)F-FDG uptake in
      the follow up PET/CT. The characteristics of patients and tumors are described
      below. The median age was 48 years (range 19-66 years). The median tumor size was
      1.9 cm (range 1.0-2.3 cm), and the median SUVmax of the pelvic mass was 5.1
      (range 3.7-7.9). The median time between initial operations and second operation
      was 13.5 months (range 8-23 months). We performed laparoscopic excision of the
      pelvic mass, and the biopsy revealed foreign body reactions with the exception of
      1 case, which contained tumor cells under the unabsorbed polylactide adhesion
      barrier. The median adhesion grade was 1 (range 0-2). CONCLUSIONS: A solitary
      pelvic mass found in the PET/CT with increased (18)F-FDG uptake after usage of a
      polylactide adhesion barrier may be an unabsorbed remnant. The adhesion barrier
      should be used with caution in patients with gynecologic malignant diseases.

PMID- 25559370
TI  - Sb-induced phase control of InAsSb nanowires grown by molecular beam epitaxy.
AB  - For the first time, we report a complete control of crystal structure in InAs(1
      x)Sb(x) NWs by tuning the antimony (Sb) composition. This claim is substantiated
      by high-resolution transmission electron microscopy combined with
      photoluminescence spectroscopy. The pure InAs nanowires generally show a mixture
      of wurtzite (WZ) and zinc-blende (ZB) phases, where addition of a small amount of
      Sb (~2-4%) led to quasi-pure WZ InAsSb NWs, while further increase of Sb (~10%)
      resulted in quasi-pure ZB InAsSb NWs. This phase transition is further evidenced
      by photoluminescence (PL) studies, where a dominant emission associated with the
      coexistence of WZ and ZB phases is present in the pure InAs NWs but absent in the
      PL spectrum of InAs0.96Sb0.04 NWs that instead shows a band-to-band emission. We
      also demonstrate that the Sb addition significantly reduces the stacking fault
      density in the NWs. This study provides new insights on the role of Sb addition
      for effective control of nanowire crystal structure.

PMID- 25559371
TI  - All my husband needed was a good physical examination.

PMID- 25559372
TI  - How do you use AAPS PharmSciTech?

PMID- 25559373
TI  - Formulation, characterisation and stabilisation of buccal films for paediatric
      drug delivery of omeprazole.
AB  - This study aimed to develop films for potential delivery of omeprazole (OME) via
      the buccal mucosa of paediatric patients. Films were prepared using
      hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA),
      carrageenan (CA) and metolose (MET) with polyethylene glycol (PEG 400) as
      plasticiser, OME (model drug) and L-arg (stabiliser). Gels (1% w/w) were prepared
      at 40 degrees C using water and ethanol with PEG 400 (0-1% w/w) and dried in an
      oven (40 degrees C). Optimised formulations containing OME and L-arg (1:1, 1:2
      and 1:3) were prepared to investigate the stabilisation of the drug. Tensile
      properties (Texture analysis, TA), physical form (differential scanning
      calorimetry, DSC; X-ray diffraction, XRD; thermogravimetric analysis, TGA) and
      surface topography (scanning electron microscopy, SEM) were investigated. Based
      on the TA results, SA and MET films were chosen for OME loading and stabilisation
      studies as they showed a good balance between flexibility and toughness.
      Plasticised MET films were uniform and smooth whilst unplasticised films
      demonstrated rough lumpy surfaces. SA films prepared from aqueous gels showed
      some lumps on the surface, whereas SA films prepared from ethanolic gels were
      smooth and uniform. Drug-loaded gels showed that OME was unstable and therefore
      required addition of L-arg. The DSC and XRD suggested molecular dispersion of
      drug within the polymeric matrix. Plasticised (0.5% w/w PEG 400) MET films
      prepared from ethanolic (20% v/v) gels and containing OME: L-arg 1:2 showed the
      most ideal characteristics (transparency, ease of peeling and flexibility) and
      was selected for further investigation. 

PMID- 25559374
TI  - Functional status at discharge and 30-day readmission risk in COPD.
AB  - BACKGROUND: Efforts to reduce 30-day readmissions are resource intensive.
      Healthcare systems need to target interventions at patients with the highest
      risk. Information on physical functioning has been found to increase the
      performance of previously published risk prediction models. We examined whether
      functional status documented during routine nursing care in the 24 h prior to
      discharge was an independent predictor of 30-day readmission risk in patients
      with COPD. METHODS: Patients from a large integrated healthcare system were
      included in this retrospective cohort study if they were hospitalized for COPD
      and discharged between January 1, 2011, and December 31, 2012, age 40+, on a
      bronchodilator or steroid inhaler, alive at discharge, and continuously enrolled
      in the health plan 12 months prior to the index admission and at least 30-days
      post discharge. Our main outcome was 30-day all-cause readmission. Functional
      status was documented as part of routine nursing care within 24 h prior to
      discharge as follows: bed bound (Level I), able to sit (Level II), stand next to
      bed (Level III), walk <50 feet (Level IV), and walk >50 feet (Level V). RESULTS:
      The sample included 2910 patients (n = 3631 index admissions) with a mean age of
      72 +/- 11. The 30-day readmission rate was 19%. Multivariate analyses showed that
      patients who were non-ambulatory at discharge (Levels I-III) were more than twice
      as likely to be re-admitted within 30-days compared to patients who were able to
      walk more than 50 feet (RR: 2.14, 95% CI 1.62-2.84, p < .001). There was no
      significant difference in readmission risk between patients classified as Level
      IV or V (p > .05). CONCLUSION: Patients with COPD who were non-ambulatory within
      24 h prior to discharge were at significantly greater risk of readmission
      compared to ambulatory patients. Functional status should be used to risk
      stratify patients for more intensive supportive interventions post discharge.

PMID- 25559375
TI  - Meta-analysis of suicide rates among psychiatric in-patients.
AB  - OBJECTIVE: To examine factors associated with the number of psychiatric
      admissions per in-patient suicide and the suicide rate per 100,000 in-patient
      years in psychiatric hospitals. METHOD: Random-effects meta-analysis was used to
      calculate pooled estimates, and meta-regression was used to examine between
      sample heterogeneity. RESULTS: Forty-four studies published between 1945 and 2013
      reported a total of 7552 in-patient suicides. The pooled estimate of the number
      of admissions per suicide calculated using 39 studies reporting 150 independent
      samples was 676 (95% CI: 604-755). Recent studies tended to report higher numbers
      of admissions per suicide than earlier studies. The pooled estimate of suicide
      rates per 100,000 in-patient years calculated using 27 studies reporting 95
      independent samples was 147 (95% CI: 138-156). Rates of suicide per 100,000 in
      patient years tended to be higher in more recent samples, in samples from regions
      with a higher whole of population suicide rate, in samples from settings with a
      shorter average length of hospital stay and in studies using coronial records to
      define suicide. CONCLUSION: Rates of in-patient suicide in psychiatric hospitals
      vary remarkably and are disturbingly high. Further research might clarify the
      extent to which patient factors and the characteristics of in-patient facilities
      contribute to the unacceptable mortality in psychiatric hospitals.

PMID- 25559376
TI  - Blue light aids in coping with the post-lunch dip: an EEG study.
AB  - The 'post-lunch dip' is a commonly experienced period of drowsiness in the
      afternoon hours. If this inevitable period can be disrupted by an environmental
      cue, the result will be enhanced workplace performance. Because blue light is
      known to be a critical cue for entraining biological rhythms, we investigated
      whether blue light illumination can be a practical strategy for coping with the
      post-lunch dip. Twenty healthy participants underwent a continuous performance
      test, during which the electroencephalogram (EEG) was recorded under four
      different illumination conditions: dark ( < 0.3 lx), 33% blue-enriched light, 66%
      blue-enriched light and white polychromatic light. As a result, exposure to blue
      enriched light during the post-lunch dip period significantly reduced the EEG
      alpha activity, and increased task performance. Since desynchronisation of alpha
      activity reflects enhancement of vigilance, our findings imply that blue light
      might disrupt the post-lunch dip. Subsequent exploration of illumination
      parameters will be beneficial for possible chronobiological and ergonomic
      applications.

PMID- 25559377
TI  - Diffusion-weighted imaging of the liver at 3 T using section-selection gradient
      reversal: emphasis on chemical shift artefacts and lesion conspicuity.
AB  - AIM: To assess the value of section-selection gradient reversal (SSGR) in liver
      diffusion-weighted imaging (DWI) by comparing it to conventional DWI with an
      emphasis on chemical shift artefacts and lesion conspicuity. MATERIALS AND
      METHODS: Forty-eight patients (29 men and 19 women; age range 33-80 years) with
      48 liver lesions underwent two DWI examinations using spectral presaturation with
      inversion recovery fat suppression with and without SSGR at 3 T. Two reviewers
      evaluated each DWI (b = 100 and b = 800 image) with respect to chemical shift
      artefacts and liver lesion conspicuity using five-point scales and performed
      pairwise comparisons between the two DWIs. The signal-to-noise ratio (SNR) of the
      liver and the lesion and the lesion-liver contrast-to-noise ratio (CNR) were also
      calculated. RESULTS: SSGR-DWI was significantly better than conventional DWI with
      respect to chemical shift artefacts and lesion conspicuity in both separate
      reviews and pairwise comparisons (p < 0.05). There were significant differences
      in the SNR of the liver (b = 100 and b = 800 images) and lesion (b = 800) between
      SSGR-DWI and conventional DWI (p < 0.05). CONCLUSION: Applying the SSGR method to
      DWI using SPIR fat suppression at 3 T could significantly reduce chemical shift
      artefacts without incurring additional acquisition time or SNR penalties, which
      leads to increased conspicuity of focal liver lesions.

PMID- 25559378
TI  - A radiological approach to benign and malignant lesions of the mandible.
AB  - There is a wide range of pathological conditions that affect the mandible.
      Although some lesions demonstrate characteristic imaging features, many of the
      pathological processes encountered in the mandible often exhibit similar imaging
      appearances resulting in uncertainty for the reporting radiologist. Many
      mandibular lesions remain impossible to distinguish without histological
      analysis. Therefore, this review aims to reassure the radiologist that although
      imaging findings may not always lead to a specific diagnosis, they narrow the
      differential diagnosis and guide further work-up. In this regard, we aim to
      provide a clinically useful framework and approach for radiologists to use when
      they encounter lesions within the mandible. 

PMID- 25559379
TI  - MRI in adult patients with aortic coarctation: diagnosis and follow-up.
AB  - Aortic coarctation is a disease that usually presents in infancy; however, a
      proportion of patients present for the first time in adulthood. These lesions
      generally require repair with either surgery or interventional techniques. The
      success of these techniques means that increasing numbers of patients are
      presenting for follow-up imaging in adulthood, whether their coarctation was
      initially repaired in infancy or as adults. Thus, the adult presenting to the
      radiologist for assessment of possible coarctation or follow-up of coarctation
      repair is not an uncommon scenario. In this review, we present details of the MRI
      protocols and MRI findings in these patients so that a confident and accurate
      assessment can be made. 

PMID- 25559380
TI  - An exploration of sports rehabilitators' and athletic rehabilitation therapists'
      views on fear of reinjury after anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Research involving long-term follow-up of patients after successful
      anterior cruciate ligament reconstruction (ACLR) has shown that return-to-sport
      rates are not as good as would be expected despite many patients' having normal
      knee-function scores. The psychological component, specifically fear of reinjury,
      plays a critical role in determining patients' return to play and is frequently
      underestimated. Little is known about the recognition and intervention from the
      therapist's perspective. AIM: To gain a greater understanding of the views of
      sports rehabilitators and athletic rehabilitation therapists on recognition of
      fear of reinjury in clients after ACLR. METHOD AND DESIGN: A qualitative
      approach, consisting of semistructured interviews with a purposive sample of 8
      participants, sports rehabilitators, or athletic rehabilitation therapists. This
      population has been largely unexamined in this context in previous research. MAIN
      FINDINGS: Thematic analysis yielded 2 main themes: communication and education.
      Participants discussed the importance of communication in the client-therapist
      relationship and how it is used in addressing misinformation and fear of
      reinjury. All participants used education in outlining the rehabilitation pathway
      and dealing with those providing social support around the client. Issues emerged
      relating to therapists' recognition of observable signs of fear of reinjury in
      the clinical setting. Overall, participants thought that fear of reinjury was not
      a barrier to return to play after ACLR. CONCLUSION: There is a need for more
      education of therapists on recognizing fear of reinjury and the appropriate use
      of psychological intervention skills as a method for dealing with this throughout
      the rehabilitation process.

PMID- 25559381
TI  - Diversity in sensory quality and determining factors influencing mandarin flavor
      liking.
AB  - We evaluated the sensory quality of 42 mandarin varieties that belong to 7
      different natural subgroups: common mandarin (Citrus reticulata Blanco),
      Clementine (Citrus clementina Hort. ex. Tan), Satsuma (Citrus unshiu Marcovitch),
      Mediterranean mandarin (Citrus deliciosa Tenore), King mandarin (Citrus nobilis
      Loureiro), and mandarin hybrids, such as tangor (Citrus reticulata * Citrus
      sinensis) and tangelo (Citrus reticulata * Citrus paradisi). Consumer flavor
      acceptance tests revealed wide diversity in flavor preferences among mandarin
      varieties and subgroups. Furthermore, descriptive flavor-analysis tests conducted
      with the aid of a trained sensory panel revealed that the 9 most preferred
      varieties had similar flavor profiles, characterized by high sweetness, moderate
      to low acidity levels, low bitterness and gumminess, strong fruity and mandarin
      flavor, and high juiciness. The average total soluble solids (TSS) and acidity
      levels among the highly preferred varieties were 13.1% and 1.1%, respectively. In
      contrast, the 8 least preferred varieties were either too sour or gummy or had
      low levels of sweetness, fruity, or mandarin flavor, and either high acidity
      levels (>1.4%) or low TSS levels (<12.0%). Pearson tests revealed significant
      positive correlations between flavor acceptance and perceptions of sweetness,
      fruitiness, and mandarin flavor, and negative correlations with acidity levels
      and perceptions of sourness, bitterness, and gumminess. Principle component
      analysis clearly distinguished between highly accepted varieties that were
      tightly correlated with high TSS levels and perceptions of sweetness fruitiness
      and mandarin flavor, as compared with the least accepted varieties that were
      correlated with high acidity levels and perceptions of sourness, bitterness, and
      gumminess. 

PMID- 25559382
TI  - The effects of oxytocin on cognitive defect caused by chronic restraint stress
      applied to adolescent rats and on hippocampal VEGF and BDNF levels.
AB  - BACKGROUND: Because brain development continues during adolescence, the effects
      of chronic stress on hippocampal changes that occur during that period are
      permanent. Oxytocin, which is synthesized in the hypothalamus and has many
      receptors in brain regions, including the hippocampus, may affect learning
      memory. This study aimed to investigate chronic restraint stress on hippocampal
      functions, and hippocampal vascular endothelial growth factor (VEGF) and brain
      derived neurotrophic factor (BDNF) levels in adolescent male and female rats and
      the role of oxytocin in these effects. MATERIAL/METHODS: Experimental groups
      included control, stress+oxytocin, and stress+saline groups. Restraint stress was
      applied to all the stress groups for 1 h/day, for 7 days. Learning-memory tests
      were performed after the 7th day. RESULTS: In the stress+oxytocin groups, the
      process of finding the platform was shorter than in others groups. The
      stress+saline groups spent less time, whereas the stress+oxytocin groups spent
      more time, on the target quadrant in the probe trial. In the stress+oxytocin
      groups thigmotaxis time (indicating anxiety) decreased, but VEGF and BDNF levels
      increased. A positive correlation was found between VEGF and BDNF levels and the
      time spent within the target quadrant. CONCLUSIONS: The results indicate that
      impaired hippocampal learning and memory loss due to chronic restraint stress can
      be positively affected by intranasal oxytocin.

PMID- 25559383
TI  - [Functional impairment, fear of falling and body composition in institutionalized
      elderly].
AB  - OBJECTIVES: To analyze changes in the aging process of institutionalized elderly
      over a 24 months period, including physical condition, fear of falling, and body
      composition. METHOD: A longitudinal, analytic and prospective study was
      implemented in 3 residential care homes for seniors. Data were collected using a
      socio-demographic and clinical questionnaire, the Rikli and Jones Senior Fitness
      Test, handgrip dynamometry and bioelectric impedance. The Portuguese version of
      the Falls Efficacy Scale was used for measure fear of falling. RESULTS: Fifty-one
      institutionalized elderly (82.5 +/- 7.4 years) were included. In the 24 months
      analysis period, functional decline was observed (P<.05) in tests: sit to stand,
      harm curl, sit and reach and Up and Go. In average falls occurred 1.7 times. Were
      observed a decrease of self-efficacy to prevent falling, and falls prevalence was
      42.1%. CONCLUSIONS: Results suggest a functional decrease, mainly in variables
      related with strength and muscular control of arms and legs, agility/dynamic
      balance and flexibility. Data don't highlight significant changes in body
      composition, however, tend to a muscle mass and bone mineral mass reduction.

PMID- 25559384
TI  - Vitamin D receptor, a tumor suppressor in skin.
AB  - Vitamin D and calcium are well-established regulators of keratinocyte
      proliferation and differentiation. Therefore, it was not a great surprise that
      deletion of the vitamin D receptor (VDR) should predispose the skin to tumor
      formation, and that the combination of deleting both the VDR and calcium sensing
      receptor (CaSR) should be especially pro-oncogenic. In this review I have
      examined 4 mechanisms that appear to underlie the means by which VDR acts as a
      tumor suppressor in skin. First, DNA damage repair is curtailed in the absence of
      the VDR, allowing mutations in DNA to accumulate. Second and third involve the
      increased activation of the hedgehog and beta-catenin pathways in the epidermis
      in the absence of the VDR, leading to poorly regulated proliferation with reduced
      differentiation. Finally, VDR deletion leads to a shift in the expression of long
      noncoding RNAs toward a more oncogenic profile. How these different mechanisms
      interact and their relative importance in the predisposition of the VDR null
      epidermis to tumor formation remain under active investigation. 

PMID- 25559385
TI  - Gairo virus, a novel arenavirus of the widespread Mastomys natalensis:
      Genetically divergent, but ecologically similar to Lassa and Morogoro viruses.
AB  - Despite its near pan-African range, the Natal multimammate mouse, Mastomys
      natalensis, carries the human pathogen Lassa virus only in West Africa, while the
      seemingly non-pathogenic arenaviruses Mopeia, Morogoro, and Luna have been
      detected in this semi-commensal rodent in Mozambique/Zimbabwe, Tanzania and
      Zambia, respectively. Here, we describe a novel arenavirus in M. natalensis from
      Gairo district of central Tanzania, for which we propose the name "Gairo virus".
      Surprisingly, the virus is not closely related with Morogoro virus that infects
      M. natalensis only 90km south of Gairo, but clusters phylogenetically with Mobala
      like viruses that infect non-M. natalensis host species in Central African
      Republic and Ethiopia. Despite the evolutionary distance, Gairo virus shares
      basic ecological features with the other M. natalensis-borne viruses Lassa and
      Morogoro. Our data show that M. natalensis, carrying distantly related viruses
      even in the same geographical area, is a potent reservoir host for a variety of
      arenaviruses. 

PMID- 25559386
TI  - Lysine metabolism in antisense C-hordein barley grains.
AB  - The grain proteins of barley are deficient in lysine and threonine due to their
      low concentrations in the major storage protein class, the hordeins, especially
      in the C-hordein subgroup. Previously produced antisense C-hordein transgenic
      barley lines have an improved amino acid composition, with increased lysine,
      methionine and threonine contents. The objective of the study was to investigate
      the possible changes in the regulation of key enzymes of the aspartate metabolic
      pathway and the contents of aspartate-derived amino acids in the nontransgenic
      line (Hordeum vulgare L. cv. Golden Promise) and five antisense C-hordein
      transgenic barley lines. Considering the amounts of soluble and protein-bound
      aspartate-derived amino acids together with the analysis of key enzymes of
      aspartate metabolic pathway, we suggest that the C-hordein suppression did not
      only alter the metabolism of at least one aspartate-derived amino acid
      (threonine), but major changes were also detected in the metabolism of lysine and
      methionine. Modifications in the activities and regulation of aspartate kinase,
      dihydrodipicolinate synthase and homoserine dehydrogenase were observed in most
      transgenic lines. Furthermore the activities of lysine alpha-ketoglutarate
      reductase and saccharopine dehydrogenase were also altered, although the extent
      varied among the transgenic lines. 

PMID- 25559387
TI  - Expression of potato S-adenosyl-L-methionine synthase (SbSAMS) gene altered
      developmental characteristics and stress responses in transgenic Arabidopsis
      plants.
AB  - S-adenosyl-L-methionine (SAM) synthase (SAMS) catalyze the biosynthesis of SAM,
      which is a precursor for ethylene and polyamines, and a methyl donor for a number
      of biomolecules. A full-length cDNA of SAMS from Solanum brevidens was expressed
      in Arabidopsis thaliana to study its physiological function. RT-PCR analysis
      showed that SbSAMS expression was enhanced significantly in S. brevidens leaves
      upon treatment with salt, mannitol, ethephon, IAA and ABA. The transgenic SbSAMS
      overexpression lines accumulated higher levels S-adenosyl homocysteine (SAHC) and
      ethylene concomitantly with increased SAM level. Expression levels of genes
      related to ethylene biosynthesis such as ACC synthase, but not polyamine
      biosynthesis genes were enhanced in SbSAMS overexpressing Arabidopsis lines. In
      addition, ABA responsive, wound and pathogen-inducible genes were upregulated in
      SbSAMS transgenic Arabidopsis plants. Transgenic Arabidopsis lines exhibited
      higher salt and drought stress tolerance compared to those of vector control.
      Based on these results we conclude that SbSAMS is expressed under abiotic stress
      to produce SAM as a broad-spectrum signal molecule to upregulate stress-related
      genes including ethylene and ABA biosynthetic pathway genes responsible for ABA,
      pathogen and wound responses.

PMID- 25559388
TI  - Resident duty hours in Canada: a survey and national statement.
AB  - Physicians in general, and residents in particular, are adapting to duty
      schedules in which they have fewer continuous work hours; however, there are no
      Canadian guidelines on duty hours restrictions. To better inform resident duty
      hour policy in Canada, we set out to prepare a set of recommendations that would
      draw upon evidence reported in the literature and reflect the experiences of
      resident members of the Canadian Association of Internes and Residents (CAIR). A
      survey was prepared and distributed electronically to all resident members of
      CAIR. A total of 1796 eligible residents participated in the survey. Of those who
      responded, 38% (601) reported that they felt they could safely provide care for
      up to 16 continuous hours, and 20% (315) said that 12 continuous hours was the
      maximum period during which they could safely provide care (n=1592). Eighty-two
      percent (1316) reported their perception that the quality of care they had
      provided suffered because of the number of consecutive hours worked (n=1598).
      Only 52% (830) had received training in handover (n=1594); those who had received
      such training reported that it was commonly provided through informal modelling.
      On the basis of these data and the existing literature, CAIR recommends that
      resident duty hours be managed in a way that does not endanger the health of
      residents or patients; does not impair education; is flexible; and does not
      violate ethical or legal standards. Further, residents should be formally trained
      in handover skills and alternative duty hour models.

PMID- 25559390
TI  - Capturing outcomes: doctor doesn't always know best.

PMID- 25559389
TI  - Inhibition of type 1 fimbriae-mediated Escherichia coli adhesion and biofilm
      formation by trimeric cluster thiomannosides conjugated to diamond nanoparticles.
AB  - Recent advances in nanotechnology have seen the development of a number of
      microbiocidal and/or anti-adhesive nanoparticles displaying activity against
      biofilms. In this work, trimeric thiomannoside clusters conjugated to nanodiamond
      particles (ND) were targeted for investigation. NDs have attracted attention as a
      biocompatible nanomaterial and we were curious to see whether the high mannose
      glycotope density obtained upon grouping monosaccharide units in triads might
      lead to the corresponding ND-conjugates behaving as effective inhibitors of E.
      coli type 1 fimbriae-mediated adhesion as well as of biofilm formation. The
      required trimeric thiosugar clusters were obtained through a convenient thiol-ene
      "click" strategy and were subsequently conjugated to alkynyl-functionalized NDs
      using a Cu(I)-catalysed "click" reaction. We demonstrated that the tri
      thiomannoside cluster-conjugated NDs (ND-Man3) show potent inhibition of type 1
      fimbriae-mediated E. coli adhesion to yeast and T24 bladder cells as well as of
      biofilm formation. The biofilm disrupting effects demonstrated here have only
      rarely been reported in the past for analogues featuring such simple glycosidic
      motifs. Moreover, the finding that the tri-thiomannoside cluster (Man3N3) is
      itself a relatively efficient inhibitor, even when not conjugated to any ND
      edifice, suggests that alternative mono- or multivalent sugar-derived analogues
      might also be usefully explored for E. coli-mediated biofilm disrupting
      properties.

PMID- 25559391
TI  - Seronegative catastrophic antiphospholipid syndrome in a young female presenting
      with a headache.
AB  - BACKGROUND: Catastrophic antiphospholipid syndrome (CAPS) is a rare disease that
      causes rapid vascular occlusion in multiple organ systems. Initial presentation
      varies depending on the organs affected. Although headache is a common complaint
      in the emergency department (ED), it is a very rare presentation of CAPS. CASE
      REPORT: A 43-year-old previously healthy woman presented to the ED with severe
      headache. Subarachnoid hemorrhage was excluded and she was discharged home. She
      returned 36 h later with diabetic ketoacidosis, hyperthyroidism, and thrombosis
      in her cerebral venous sinus, aorta and splenic artery. She was treated with
      heparin, steroids, plasmapharesis, and i.v. immunoglobulin, after which she
      improved. This constellation of symptoms is highly suggestive of CAPS initiated
      by a polyglandular autoimmune syndrome, despite negative serology. WHY SHOULD AN
      EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although a rare cause of headache, CAPS is
      a potentially fatal disease that requires early identification and initiation of
      appropriate treatment.

PMID- 25559394
TI  - Ethnoecology of the palm Brahea dulcis (Kunth) Mart. in central Mexico.
AB  - BACKGROUND: There have been few studies on the sustainable use of non-timber
      forest products in arid and semi-arid zones. The palm Brahea dulcis has been one
      of the most important resources in semi-arid Mesoamerica, since pre-Hispanic
      times. Currently, some populations grow within protected natural areas,
      representing both a challenge and an opportunity for local development. This
      ethnoecological study of B. dulcis in central Mexico aimed to evaluate their
      uses, harvesting context, and potential for exploitation, in order to give
      practical advice on their best use and management. METHODS: Ethnographic and
      ecological information was obtained in Barranca de Metztitlan Biosphere Reserve
      and Valle del Mezquital, Mexico. We studied the population structure and density;
      additionally, we evaluated the rate of leaf production, leaf renewal rate,
      percent survival of new leaves, the development of reproductive structures and
      performed a one-year defoliation experiment (involving a control and four
      treatments including a mix of semiannual and annual frequency of harvest and
      removal of two new leaves and/or two mature leaves). RESULTS: Twenty uses of the
      palm were recorded in the study area. Religious/symbolic and handicraft uses are
      highlighted. The population density of this species was the highest reported for
      the genus (1244 +/- 231.7 ind/ha). The leaf production rate was the highest
      reported for arborescent palms of the Americas (11.83 +/- 0.036
      leaves/individual/year). The sexual reproductive cycle was 2.3 years long. A one
      year defoliation experiment did not show statistically significant differences.
      Recommendations include: 1) implement management focused on increasing the
      abundance and quality of this useful resource in Metztitlan; 2) employ a strategy
      of focusing on ethnicity and gender in promoting their exploitation; 3) learn
      from theoretical frameworks of other non timber forest product studies.
      CONCLUSIONS: We propose that Brahea dulcis is the palm with the highest potential
      for sustainable use in the arid and semi-arid zones of Mexico. The challenge to
      improving management includes simplifying the legal protection framework,
      promoting uses and developing a market strategy. Collaborations to share
      experiences with peasant farmers from Guerrero is recommended. We further
      recommend the development of a governmental strategy to enhance and reassess this
      important resource.

PMID- 25559395
TI  - Microdiplanol and microdiplane: a new m-anisaldehyde and a new 24
      methylcholestanol derivative from the endophytic fungus Microdiplodia sp.
AB  - Phytochemical investigation of the endophytic fungus Microdiplodia sp. afforded a
      new m-anisaldehyde derivative named microdiplanol (1) and a new 24
      methylcholestanol derivative named microdiplane (2). Their structures were
      confirmed by a comprehensive analysis of 1D and 2D NMR and mass spectrometric
      data. 

PMID- 25559396
TI  - Poly(A)(+) mRNA-binding protein Tudor-SN regulates stress granules aggregation
      dynamics.
AB  - Stress granules (SGs) and processing bodies (PBs) comprise the main types of
      cytoplasmic RNA foci during stress. Our previous data indicate that knockdown of
      human Tudor staphylococcal nuclease (Tudor-SN) affects the aggregation of SGs.
      However, the precise molecular mechanism has not been determined fully. In the
      present study, we demonstrate that Tudor-SN binds and colocalizes with many core
      components of SGs, such as poly(A)(+) mRNA binding protein 1, T-cell internal
      antigen-1-related protein and poly(A)(+) mRNA, and SG/PB sharing proteins
      Argonaute 1/2, but not PB core proteins, such as decapping enzyme 1 a/b,
      confirming that Tudor-SN is an SG-specific protein. We also demonstrate that the
      Tudor-SN granule actively communicates with the nuclear and cytosolic pool under
      stress conditions. Tudor-SN can regulate the aggregation dynamics of poly(A)(+)
      mRNA-containing SGs and selectively stabilize the SG-associated mRNA during
      cellular stress. 

PMID- 25559397
TI  - Counteracting effect of threat on reward enhancements during working memory.
AB  - Cognitive performance has been shown to be enhanced when performance-based
      rewards are at stake. On the other hand, task-irrelevant threat processing has
      been shown to have detrimental effects during several cognitive tasks. Crucially,
      the impact of reward and threat on cognition has been studied largely
      independently of one another. Hence, our understanding of how reward and threat
      simultaneously contribute to performance is incomplete. To fill in this gap, the
      present study investigated how reward and threat interact with one another during
      a cognitive task. We found that threat of shock counteracted the beneficial
      effect of reward during a working memory task. Furthermore, individual
      differences in self-reported reward-sensitivity and anxiety were linked to the
      extent to which reward and threat interacted during behaviour. Together, the
      current findings contribute to a limited but growing literature unravelling how
      positive and negative information processing jointly influence cognition. 

PMID- 25559398
TI  - A highly sensitive x-ray imaging modality for hepatocellular carcinoma detection
      in vitro.
AB  - Innovations that improve sensitivity and reduce cost are of paramount importance
      in diagnostic imaging. The novel x-ray imaging modality called spatial frequency
      heterodyne imaging (SFHI) is based on a linear arrangement of x-ray source,
      tissue, and x-ray detector, much like that of a conventional x-ray imaging
      apparatus. However, SFHI rests on a complete paradigm reversal compared to
      conventional x-ray absorption-based radiology: while scattered x-rays are
      carefully rejected in absorption-based x-ray radiology to enhance the image
      contrast, SFHI forms images exclusively from x-rays scattered by the tissue. In
      this study we use numerical processing to produce x-ray scatter images of
      hepatocellular carcinoma labeled with a nanoparticle contrast agent. We
      subsequently compare the sensitivity of SFHI in this application to that of both
      conventional x-ray imaging and magnetic resonance imaging (MRI). Although SFHI is
      still in the early stages of its development, our results show that the
      sensitivity of SFHI is an order of magnitude greater than that of absorption
      based x-ray imaging and approximately equal to that of MRI. As x-ray imaging
      modalities typically have lower installation and service costs compared to MRI,
      SFHI could become a cost effective alternative to MRI, particularly in areas of
      the world with inadequate availability of MRI facilities. 

PMID- 25559399
TI  - Major prognostic role of Ki67 in localized adrenocortical carcinoma after
      complete resection.
AB  - BACKGROUND: Recurrence of adrenocortical carcinoma (ACC) even after complete (R0)
      resection occurs frequently. OBJECTIVE: The aim of this study was to identify
      markers with prognostic value for patients in this clinical setting. DESIGN,
      SETTING, AND PARTICIPANTS: From the German ACC registry, 319 patients with the
      European Network for the Study of Adrenal Tumors stage I-III were identified. As
      an independent validation cohort, 250 patients from three European countries were
      included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinical, histological,
      and immunohistochemical markers were correlated with recurrence-free (RFS) and
      overall survival (OS). RESULTS: Although univariable analysis within the German
      cohort suggested several factors with potential prognostic power, upon
      multivariable adjustment only a few including age, tumor size, venous tumor
      thrombus (VTT), and the proliferation marker Ki67 retained significance. Among
      these, Ki67 provided the single best prognostic value for RFS (hazard ratio [HR]
      for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P
      < .0001) which was confirmed in the validation cohort. Accordingly, clinical
      outcome differed significantly between patients with Ki67 <10%, 10-19%, and >=20%
      (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs
      113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor
      size, VTT, and Ki67 were established. Although these scores discriminated
      slightly better between subgroups, there was no clinically meaningful advantage
      in comparison with Ki67 alone. CONCLUSION: This largest study on prognostic
      markers in localized ACC identified Ki67 as the single most important factor
      predicting recurrence in patients following R0 resection. Thus, evaluation of
      Ki67 indices should be introduced as standard grading in all pathology reports of
      patients with ACC.

PMID- 25559400
TI  - Fasting hyperglycemia predicts lower rates of weight gain by increased energy
      expenditure and fat oxidation rate.
AB  - CONTEXT: Increased adiposity and insulin resistance are associated with
      hyperglycemia and previous studies have reported that higher glucoses are
      associated with lower rates of weight gain. One possible mechanism is via
      increased energy expenditure (EE). OBJECTIVE: To assess the relationships between
      changes in EE during spontaneous weight gain and concomitant changes in glucose
      levels. DESIGN AND PARTICIPANTS: Body composition, metabolic, and glycemic data
      were available from nondiabetic Native Americans who underwent two measurements
      of 24-h EE during eucaloric feeding in a metabolic chamber (N = 144; time between
      measurements: 5.0 +/- 3.3 years) or resting EE by ventilated hood system during
      the euglycemic-hyperinsulinemic clamp (N = 261; 4.5 +/- 3.2 years). Long-term
      follow-up data (8.3 +/- 4.3 years) for weight and body composition were available
      in 131 and 122 subjects, respectively. MAIN OUTCOME MEASURES: Twenty four hour EE
      and respiratory quotient (RQ), resting (RMR), and sleeping (SMR) metabolic rates,
      glucose, and insulin levels, basal glucose output (BGO). RESULTS: Weight gain
      associated increase in fasting plasma glucose (FPG) levels was accompanied with
      decreased 24-h RQ (partial R = -0.24, P = .002) and increased 24-h EE, RMR, SMR,
      and fat oxidation after accounting for changes in body composition (partial R:
      0.12 to 0.19, all P <= .05). Upon weight gain, BGO tended to increase (P = .07),
      while insulin infusion induced a decrease in EE (P = .04). Higher baseline FPG
      predicted lower rates of future weight gain (partial R = -0.18, P = .04).
      CONCLUSIONS: Higher FPG after weight gain was associated with greater-than
      expected increase in EE. The rise in BGO and the insulin-induced EE suppression
      at follow-up indicate that increased hepatic gluconeogenesis may be an important
      mediator of EE changes associated with weight gain.

PMID- 25559401
TI  - Postpartum microalbuminuria after gestational diabetes: the impact of current
      glucose tolerance status.
AB  - CONTEXT: It has been reported that women with a history of gestational diabetes
      mellitus (GDM) have an increased risk of microalbuminuria compared with that of
      their peers. Because previous GDM predicts an increased risk of prediabetes,
      which itself is associated with microalbuminuria, we hypothesized that current
      glucose intolerance may confound any association between GDM and
      microalbuminuria. OBJECTIVE: The purpose of this study was to evaluate the
      relative impact of gestational and current dysglycemia on postpartum
      microalbuminuria in a cohort of women reflecting the full spectrum of gestational
      glucose tolerance from normal to mildly abnormal to GDM.
      DESIGN/SETTING/PARTICIPANTS: In this prospective observational cohort study, 320
      women underwent a glucose challenge test (GCT) and an oral glucose tolerance test
      (OGTT) in pregnancy, which identified 100 women with GDM, 58 with gestational
      impaired glucose tolerance, 90 with an abnormal GCT but a normal OGTT, and 72
      with a normal GCT and OGTT. At 3 years postpartum, they underwent measurement of
      urine microalbumin and a repeat OGTT that identified 63 women with glucose
      intolerance (prediabetes/diabetes). RESULTS: The postpartum urine microalbumin to
      creatinine ratio did not differ among the 4 gestational glucose tolerance groups
      (P = .23). Furthermore, on logistic regression analysis, GDM did not
      independently predict an elevated urine microalbumin to creatinine ratio of >=1.5
      g/mol of creatinine (odds ratio, 0.43; 95% confidence interval, 0.17-1.11), after
      adjustment for age, ethnicity, family history of diabetes, body mass index, blood
      pressure, estimated glomerular filtration rate, and current glucose intolerance.
      In contrast, current glucose intolerance independently predicted a urine
      microalbumin to creatinine ratio of >=1.5 (odds ratio, 3.4; 95% confidence
      interval, 1.4-8.2, P = .005). CONCLUSION: Current glucose intolerance, rather
      than previous GDM, may be associated with an increased risk of microalbuminuria
      in the early postpartum years.

PMID- 25559402
TI  - Expanding the phenotypic spectrum and variability of endocrine abnormalities
      associated with TUBB3 E410K syndrome.
AB  - CONTEXT: A heterozygous de novo c.1228G>A mutation (E410K) in the TUBB3 gene
      encoding the neuronal-specific beta-tubulin isotype 3 (TUBB3) causes the TUBB3
      E410K syndrome characterized by congenital fibrosis of the extraocular muscles
      (CFEOM), facial weakness, intellectual and social disabilities, and Kallmann
      syndrome (anosmia with hypogonadotropic hypogonadism). All TUBB3 E410K subjects
      reported to date are sporadic cases. OBJECTIVE: This study aimed to report the
      clinical, genetic, and molecular features of a familial presentation of the TUBB3
      E410K syndrome. DESIGN: Case report of a mother and three affected children with
      clinical features of the TUBB3 E410K syndrome. SETTING: Academic Medical Center.
      MAIN OUTCOME MEASURES: Genetic analysis of the TUBB3 gene and clinical evaluation
      of endocrine and nonendocrine phenotypes. RESULTS: A de novo TUBB3 c.1228G>A
      mutation arose in a female proband who displayed CFEOM, facial weakness,
      intellectual and social disabilities, and anosmia. However, she underwent normal
      sexual development at puberty and had three spontaneous pregnancies with
      subsequent autosomal-dominant inheritance of the mutation by her three boys. All
      sons displayed nonendocrine features of the TUBB3 E410K syndrome similar to their
      mother but, in addition, had variable features suggestive of additional endocrine
      abnormalities. CONCLUSIONS: This first report of an autosomal-dominant
      inheritance of the TUBB3 c.1228G>A mutation in a family provides new insights
      into the spectrum and variability of endocrine phenotypes associated with the
      TUBB3 E410K syndrome. These observations emphasize the need for appropriate
      clinical evaluation and complicate genetic counseling of patients and families
      with this syndrome.

PMID- 25559403
TI  - Development- and age-related alterations in the expression of AMPA receptor
      subunit GluR2 and its trafficking proteins in the hippocampus of male mouse
      brain.
AB  - AMPA type glutamate receptor (AMPAR) on the post synaptic membrane plays
      important role in the process of synaptic plasticity involving various
      scaffolding and trafficking proteins. However, their alterations during
      development- and aging are not well understood. Here, we report that the
      expression of AMPAR-GluR2 subunit is gradually up regulated in the hippocampus
      from 0 day to adult (20 week) and down regulated thereafter in 70 week old male
      mice. This pattern of GluR2 during development (0-, 7- and 15 day), maturation
      (45 day) and adult age resembles with similar expression pattern of the
      scaffolding protein PSD95. Expression pattern of Stargazin (TARPgamma-2) largely
      follows almost similar pattern up to adult age but is up regulated in old age.
      Pattern of PICK1 expression, however, is opposite to our GluR2 data till adult
      age but its expression is significantly down regulated in old age. Our data on
      alterations in the expression of GluR2 in the hippocampus during development and
      aging indicates a high- and low positive correlations with PSD95 and Stargazin,
      respectively whereas negative correlation with PICK1 except in old age where
      expression of Stargazin is higher and that of PICK1 is lower. Our findings
      suggest that increasing expression pattern of GluR2 during developmental periods
      and at adult age may be associated with achieving cognitive abilities whereas its
      low expression in old age may be linked with cognitive decline and proteins like
      PSD95, Stargazin and PICK1 might be differentially associated with development-
      and age-dependent alterations in AMPAR-dependent synaptic plasticity and hence
      learning and memory.

PMID- 25559404
TI  - Differential expression of perilipin 2 and 5 in human skeletal muscle during
      aging and their association with atrophy-related genes.
AB  - Sarcopenia, the progressive loss of muscle mass and strength, is a phenomenon
      characterizing human aging whose etiology is still not clear. While there is
      increasing evidence for the influence of inter-muscular adipose tissue
      infiltration in the development of sarcopenia, much less is known about a
      possible role for intra-muscular triglycerides (IMTG). IMTG accumulate in form of
      lipid droplets decorated by proteins such as Perilipins (Plins). In skeletal
      muscle the most abundant are Plin2 and Plin5. In this study we compared the
      expression of these two Plins in Vastus lateralis muscle samples of subjects of
      different age, both healthy donors (HD) and patients with limited lower limb
      mobility (LLMI). These latter are characterized by a condition of chronic
      physical inactivity. Plin2 expression resulted higher in old age for both HD and
      LLMI patients, while Plin5 slightly decreased only in LLMI patients. Moreover, in
      these patients, only Plin2 was associated with the decrease of muscle strength
      and the expression of factors related to muscle atrophy (MuRF1, Atrogin and p53).
      An increase in Plin2 and a concomitant decrease of Plin5 was also observed when
      we considered animal model of disuse-induced muscle atrophy. As a whole, these
      data indicate that Plin2 and Plin5 have a different expression pattern during
      muscle aging and inactivity, and only Plin2 appears to be associated with
      functional alterations of the muscle.

PMID- 25559405
TI  - Crosstalk between the microbiome and cancer cells by quorum sensing peptides.
AB  - To date, the precise role of the human microbiome in health and disease states
      remains largely undefined. Complex and selective crosstalk systems between the
      microbiome and mammalian cells are also not yet reported. Research up till now
      mainly focused on bacterial synthesis of virulence factors, reactive
      oxygen/nitrogen species (ROS/RNS) and hydrogen sulphide, as well as on the
      activation of exogenous mutagen precursors by intestinal bacteria. We discovered
      that certain quorum sensing peptides, produced by bacteria, interact with
      mammalian cells, in casu cancer cells: Phr0662 (Bacillus sp.), EntF-metabolite
      (Enterococcus faecium) and EDF-derived (Escherichia coli) peptides initiate HCT
      8/E11 colon cancer cell invasion, with Phr0662 also promoting angiogenesis. Our
      findings thus indicate that the human microbiome, through their quorum sensing
      peptides, may be one of the factors responsible for cancer metastasis. 

PMID- 25559406
TI  - Polygenic expression of teratozoospermia and normal fertility in B10.MOL-TEN1
      mouse strain.
AB  - Subfertility and infertility are two major reproductive health problems in human
      and domestic animals. The contribution of the genotype to these conditions is
      poorly understood. To examine the genetic basis of male subfertility, we analyzed
      its relationship to sperm morphology in B10.MOL-TEN1 mice, which shows high
      frequencies (about 50%) of morphologically abnormal sperm. Drastic histological
      changes were also found in the testis of the B10.MOL-TEN1. Segregation analysis
      showed that the abnormal sperm phenotype in B10.MOL-TEN1 was inherited and was
      predictably controlled by at least three loci. We also found that male fertility
      of this strain was normal. These findings indicate a complicated relationship
      between sperm morphology and male subfertility. 

PMID- 25559407
TI  - Magnetic and microwave absorption properties of self-assemblies composed of core
      shell cobalt-cobalt oxide nanocrystals.
AB  - Core-shell structure cobalt-cobalt oxide nanocomposites were directly synthesized
      via annealing Co nanocrystals in air at 300  degrees C. Their microstructure and
      magnetic properties were characterized by XRD, TEM, XPS and VSM, respectively.
      The microwave absorbing properties of the nanocomposite powders by dispersing
      them in wax were investigated in the 2-18 GHz frequency range. The sample that
      was annealed for 1 h exhibits the maximum reflection loss of -30.5 dB and a
      bandwidth of less than -10 dB covering the 12.6-17.3 GHz range with the coating
      thickness of only 1.7 mm. At the same thickness, the sample annealed for 3 h
      exhibits the maximum reflection loss of -24 dB and a bandwidth that almost covers
      the whole X-band (8-11.5 GHz). With increase in the insulating cobalt oxide
      shell, the enhanced permeability could contribute to the decrease of eddy current
      loss, and the permittivity could be easily adjusted; thus, the microwave
      absorption properties of the cobalt oxide nanocrystals could be easily adjusted. 

PMID- 25559409
TI  - Commentary: Mexico: moving from universal health coverage towards health care for
      all.

PMID- 25559408
TI  - Severe Hypocalcemia Associated With Denosumab in Metastatic Castration-Resistant
      Prostate Cancer: Risk Factors and Precautions for Treating Physicians.

PMID- 25559410
TI  - Strategy for recruitment and factors associated with motivation and satisfaction
      in a randomized trial with 210 healthy volunteers without financial compensation.
AB  - BACKGROUND: The aim was to describe a strategy for recruitment of healthy
      volunteers (HV) to a randomized trial that assessed the efficacy of different
      telephone techniques to assist HV in performing cardiac massage for vital
      emergency. Participation in the randomized trial was not financially compensated,
      however HV were offered emergency first-aid training. We also studied factors
      associated with HV motivation and satisfaction regarding participation in the
      trial. METHODS: Strategy for recruitment of 210 HV aged 18 to 60 years was based
      on: (1) the updated records of all telephone number since January 2000 of HV
      registered in the Rouen Clinical Investigation Centre HV database, (2) a
      communication campaign for the general public focussing on posters and media
      advertisements. Data on the recruitment, socio-demographics, motivation and
      satisfaction of the 210 HV were collected by anonymous self-administered
      questionnaire. RESULTS: Of the 210 HV included, 63.3% (n = 133) were recruited
      from the HV database and 36.7% (n = 77) by the communication campaign. On the one
      hand, the HV database enabled screening of 1315 HV, 54.8% (n = 721) of whom were
      reached by phone, 55.2% (n = 398) of these latter accepted to participate in the
      study and 10.1% of the initial screening (n = 133) were finally included. One the
      other hand, for the 77 HV not recruited from the HV database, word-of-mouth
      (56.1%) was the main means of recruitment. The male/female ratio of the 210 HV
      was 0.5 and mean age 43.5 years (Standard Deviation = 12.4). The main motivations
      given for participating in the trial were to support research (87.6%) and receive
      emergency first-aid training (85.7%). Overall satisfaction with the welcome
      process was significantly higher for older HV (46-60 years) (adjusted odds ratio
      (AOR): 3.44; 95% confidence interval (95% CI): 1.48-7.99), and for HV in
      management jobs (AOR: 4.26; 95% CI: 1.22-14.87). Satisfaction with protocol
      management was higher for women (AOR: 2.33; 95% CI: 1.18-4.60) and for older HV
      (46-60 years) (AOR: 4.76; 95% CI: 1.97-11.52). CONCLUSIONS: Recruitment of non
      compensated HV required broad screening with a primary HV database alongside word
      of-mouth communication which seemed more efficient than media advertising. To
      enhance HV recruitment to randomized trials without financial compensation it
      seems crucial to provide them not only with a direct interest but also to ensure
      their satisfaction.

PMID- 25559411
TI  - [Clinical pathway for hip fracture patients].
AB  - INTRODUCTION: Hip fracture in the elderly often occurs in patients with high co
      morbidity. Effective management requires a comprehensive and multidisciplinary
      approach. PURPOSE: To evaluate the effect of a quality improvement intervention
      in the detection and treatment of complications in elderly patients admitted for
      hip fracture. MATERIAL AND METHODS: A comparative study was conducted between two
      groups of patients admitted for hip fracture prior to 2010, and after a quality
      improvement intervention in 2013. The intervention consisted of implementing
      improved multidisciplinary measures in accordance with recent scientific
      evidence. The degree of compliance of the implemented measures was quantified.
      RESULTS: Patients admitted due to hip fracture in 2010 (216 patients) and 2013
      (196 patients) were similar in age, sex, Barthel Index, and a reduced Charlson
      Index, although there were more comorbidities in 2013. After implementation of
      the protocols, the detection of delirium, malnutrition, anemia, and electrolyte
      disturbances increased. A larger number of patients in 2013 were precribed
      intravenous iron (24% more) and osteoporosis treatment (61.3% more). The average
      stay was reduced by 45.3% and surgical delay by 29.4%, achieving better
      functional efficiency. CONCLUSION: The implementation of a clinical pathway in
      geriatric patients with hip fracture is useful to detect and treat complications
      at an early stage, and to reduce pre-operative and overall stay, all without a
      negative clinical or functional impact.

PMID- 25559412
TI  - In vitro and in vivo immunostimulatory activity of an exopolysaccharide-enriched
      fraction from Bacillus subtilis.
AB  - AIMS: The aim of this study was to investigate the immunostimulatory effects of
      an exopolysaccharide-enriched fraction obtained from Bacillus subtilis J92 (B
      EPS). METHODS AND RESULTS: To determine the immunostimulatory activities of B
      EPS, we used IFN-gamma-primed RAW 264.7 macrophages and CD3/CD28-stimulated
      splenocytes. Increases in the levels of NO and many cytokines, such as, TNF
      alpha, IL-6, and IL-1beta, were observed in IFN-gamma-primed RAW 264.7
      macrophages by Griess reaction and ELISAs respectively. Using Western blotting
      and qRT-PCR, we found that B-EPS increased the protein and mRNA expressions of
      iNOS and the mRNA expressions of TNF-alpha, IL-6, and IL-1beta. A reporter gene
      assay and EMSA revealed that B-EPS up-regulated the transcriptional activity of
      NF-kappaB by increasing its DNA binding and nuclear translocation. Pretreatment
      with NF-kappaB inhibitors, that is, BAY11-7082 and PDTC, decreased NO production
      in IFN-gamma-primed RAW 264.7 macrophages by B-EPS. Furthermore, B-EPS increased
      the proliferation of and cytokine (IL-2 and IFN-gamma) production by CD3/CD28
      stimulated splenocytes. In a cyclophosphamide-induced immunosuppressed mouse
      model, B-EPS (5, 15 or 45 mg kg(-1) , p.o.) restored thymus and spleen indices. B
      EPS also inhibited cyclophosphamide-induced reductions in neutrophil and
      lymphocyte numbers. CONCLUSIONS: B-EPS improves immune function by regulating
      immunological parameters in IFN-gamma-primed macrophages, CD3/CD28-stimulated
      splenocytes, and in cyclophosphamide-induced immunosuppressed mice. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study suggests that the exopolysaccharides secreted
      by B. subtilis J92 could be used as immune stimulants.

PMID- 25559413
TI  - The Social Values of Aggressive-Prosocial Youth.
AB  - Recent research has identified youth who utilize both aggressive and prosocial
      behavior with peers. Although the social values and motivations associated with
      aggression and prosocial behavior have been well studied, the values of youth who
      utilize both aggression and prosocial behavior are unknown. The current study
      identified groups of adolescents based on peer nominations of aggression and
      prosocial behavior from both Israel (n = 569; 56.94% Arab, 43.06% Jewish; 53.78%
      female) and the United States (n = 342; 67.54% African-American; 32.46% European
      American; 50.88% female). Self-enhancement, self-transcendence, openness-to
      change, and conservation values predicted behavioral group membership. Power
      values predicted membership in the aggressive group relative to the aggressive
      prosocial, prosocial, and low-both groups. For Israeli boys, openness-to-change
      values predicted membership in the aggressive-prosocial group relative to the
      prosocial group. The values of aggressive-prosocial youth were more similar to
      the values of prosocial peers than to aggressive peers, suggesting that
      motivational interventions for aggressive-prosocial youth should differ in
      important ways than those for aggressive youth.

PMID- 25559414
TI  - Contextual Specificity in the Relationship between Maternal Autonomy Support and
      Children's Socio-emotional Development: A Longitudinal Study from Preschool to
      Preadolescence.
AB  - The benefits of an autonomy supportive environment have been established as a key
      component in children's development at various ages. Nonetheless, research
      examining the outcomes of early autonomy supportive environments has largely
      neglected socio-emotional development. The first objective of the present
      longitudinal study was to examine the socio-emotional outcomes associated with
      maternal autonomy support during the preschool period. Second, we explored the
      contextual specificity of the relationships between maternal autonomy support and
      children's later socio-emotional outcomes. Finally, we investigated the indirect
      effect of maternal autonomy support on children's later socio-emotional outcomes
      through earlier children's socio-emotional outcomes. Sixty-six mothers and their
      pre-school aged children (41 girls) were followed during preschool (Time 1),
      elementary school (Time 2) and preadolescence (Time 3). Maternal autonomy support
      (Time 1) was measured in two contexts (free-play and interference task) using
      observational coding. Furthermore, the children's internalizing and externalizing
      problems as well as their social competence were measured at Times 2 and 3. The
      results revealed the importance of maternal autonomy support during preschool for
      children's later socio-emotional development, especially during challenging
      contexts, and the mediating role of children's socio-emotional outcomes during
      elementary school in the link between maternal autonomy support during the
      preschool years and children's later socio-emotional outcomes during
      preadolescence. The results highlight the contextual specificity of the
      relationship between maternal autonomy support and children's later socio
      emotional development and reveal one of the mechanisms through which the effect
      of early childhood parental autonomy support on children's later socio-emotional
      development is carried forward over time. 

PMID- 25559415
TI  - Cancer statistics, 2015.
AB  - Each year the American Cancer Society estimates the numbers of new cancer cases
      and deaths that will occur in the United States in the current year and compiles
      the most recent data on cancer incidence, mortality, and survival. Incidence data
      were collected by the National Cancer Institute (Surveillance, Epidemiology, and
      End Results [SEER] Program), the Centers for Disease Control and Prevention
      (National Program of Cancer Registries), and the North American Association of
      Central Cancer Registries. Mortality data were collected by the National Center
      for Health Statistics. A total of 1,658,370 new cancer cases and 589,430 cancer
      deaths are projected to occur in the United States in 2015. During the most
      recent 5 years for which there are data (2007-2011), delay-adjusted cancer
      incidence rates (13 oldest SEER registries) declined by 1.8% per year in men and
      were stable in women, while cancer death rates nationwide decreased by 1.8% per
      year in men and by 1.4% per year in women. The overall cancer death rate
      decreased from 215.1 (per 100,000 population) in 1991 to 168.7 in 2011, a total
      relative decline of 22%. However, the magnitude of the decline varied by state,
      and was generally lowest in the South (~15%) and highest in the Northeast
      (>=20%). For example, there were declines of 25% to 30% in Maryland, New Jersey,
      Massachusetts, New York, and Delaware, which collectively averted 29,000 cancer
      deaths in 2011 as a result of this progress. Further gains can be accelerated by
      applying existing cancer control knowledge across all segments of the population.

PMID- 25559416
TI  - Performance improvement of lithium manganese phosphate by controllable morphology
      tailoring with acid-engaged nano engineering.
AB  - Olivine-type lithium manganese phosphate (LiMnPO4) has been considered as a
      promising cathode for next-generation Li-ion batteries. Preparation of high
      performance LiMnPO4 still remains a great challenge because of its intrinsically
      low Li-ion/electronic conductivity. In this work, significant performance
      enhancement of LiMnPO4 has been realized by a controllable acid-engaged
      morphology tailoring from large spindles into small plates. We find that acidity
      plays a critical role in altering the morphology of the LiMnPO4 crystals. We also
      find that size decrease and plate-like morphology are beneficial for the
      performance improvement of LiMnPO4. Among the plate-like samples, the one with
      the smallest size shows the best electrochemical performance. After carbon
      coating, it can deliver high discharge capacities of 104.0 mAh g(-1) at 10 C and
      85.0 mAh g(-1) at 20 C. After 200 cycles at 1 C, it can still maintain a high
      discharge capacity of 106.4 mAh g(-1), showing attractive applications in high
      power and high-energy Li-ion batteries. 

PMID- 25559417
TI  - Sonochemical synthesis of Au nanowires in the III-I oxidation state bridged by
      4,4'-dicyanamidobiphenyl and their application as selective CO gas sensors.
AB  - In this research, Au nanowires, gold-containing polymers of the formula [(Au(i)
      NCN-R-NCN-Au(iii)-NCN-R-NCN-)]n; R: biphenyl (or NCN-R-NCN: 4,4'
      dicyanamidobiphenyl (bpH2)), have been synthesized by a sonochemical process. X
      ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), FT-IR, UV-Vis,
      (1)H-NMR spectroscopies, elemental analysis, scanning electron microscopy (SEM)
      and transmission electron microscopy (TEM) were performed for the structural
      characterization of Au nanowires. The thermal stability of Au nanowires was
      investigated by thermogravimetric analysis (TGA). Typically, nanowires have an
      average width of 20-100 nm, and a length of up to several microns. In addition,
      Au nanowires are used in the fabrication of gas sensors. These nanosensors
      exhibit characteristics of high sensitivity to CO with the determination limit at
      1 ppm at room temperature. Furthermore, the nanosensors exhibit a good selective
      determination of CO under exposure to CH4 and NO2 even at 1000 ppm; they can be
      used to detect low concentrations of CO at room temperature. 

PMID- 25559418
TI  - US federal cocaine essential ('precursor') chemical regulation impacts on US
      cocaine availability: an intervention time-series analysis with temporal
      replication.
AB  - BACKGROUND AND AIMS: Research shows that essential/precursor chemical controls
      have had substantial impacts on US methamphetamine and heroin availability. This
      study examines whether US federal essential chemical regulations have impacted US
      cocaine seizure amount, price and purity-indicators of cocaine availability.
      DESIGN: Autoregressive integrated moving average (ARIMA)-intervention time-series
      analysis was used to assess the impacts of four US regulations targeting cocaine
      manufacturing chemicals: potassium permanganate/selected solvents, implemented
      October 1989 sulfuric acid/hydrochloric acid, implemented October 1992; methyl
      isobutyl ketone, implemented May 1995; and sodium permanganate, implemented
      December 2006. Of these chemicals, potassium permanganate and sodium permanganate
      are the most critical to cocaine production. SETTING: Conterminous United States
      (January 1987-April 2011). MEASUREMENTS: Monthly time-series: purity-adjusted
      cocaine seizure amount (in gross weight seizures < 6000 grams), purity-adjusted
      price (all available seizures), and purity (all available seizures). DATA SOURCE:
      System to Retrieve Information from Drug Evidence. FINDINGS: The 1989 potassium
      permanganate/solvents regulation was associated with a seizure amount decrease
      (change in series level) of 28% (P < 0.05), a 36% increase in price (P < 0.05)
      and a 4% decrease in purity (P < 0.05). Availability recovered in 1-2 years. The
      2006 potassium permanganate regulation was associated with a 22% seizure amount
      decrease (P < 0.05), 100% price increase (P < 0.05) and 35% purity decrease (P <
      0.05). Following the 2006 regulation, essentially no recovery occurred to April
      2011. The other two chemical regulations were associated with statistically
      significant but lesser declines in indicated availability. CONCLUSIONS: In the
      United States, essential chemical controls from 1989 to 2006 were associated with
      pronounced downturns in cocaine availability.

PMID- 25559419
TI  - Engineering aspects of rate-related processes in food manufacturing.
AB  - Many rate-related phenomena occur in food manufacturing processes. This review
      addresses four of them, all of which are topics that the author has studied in
      order to design food manufacturing processes that are favorable from the
      standpoint of food engineering. They include chromatographic separation through
      continuous separation with a simulated moving adsorber, lipid oxidation kinetics
      in emulsions and microencapsulated systems, kinetic analysis and extraction in
      subcritical water, and water migration in pasta. 

PMID- 25559420
TI  - Alipogene tiparvovec: a review of its use in adults with familial lipoprotein
      lipase deficiency.
AB  - Alipogene tiparvovec (Glybera(r); AMT-011, AAV1-LPL(S447X)) is an adeno
      associated virus serotype 1-based gene therapy for adult patients with familial
      lipoprotein lipase (LPL) deficiency (LPLD) and suffering from severe or multiple
      pancreatitis attacks despite dietary fat restrictions. It is administered as a
      one-time series of intramuscular injections in the legs. LPLD, a rare autosomal
      recessive disorder, results in hyperchylomicronaemia and severe
      hypertriglyceridaemia, which in turn, are associated with an increased risk of
      clinical complications, the most debilitating of which is recurrent severe and
      potentially life-threatening pancreatitis. In clinical studies (n = 27 patients),
      one-time administration of alipogene tiparvovec was associated with significant
      reductions in plasma triglyceride levels during the 12 or 14 week study period
      post administration. Although triglyceride levels returned to pre-treatment
      levels within 16-26 weeks after administration, patients had sustained
      improvements in postprandial chylomicron metabolism, with sustained expression of
      functional copies of the LPL (S477X) gene and of biologically active LPL in
      skeletal muscle. Moreover, after up to 6 years' follow-up post administration,
      there were clinically relevant reductions in the incidence of documented
      pancreatitis and acute abdominal pain events consistent with pancreatitis.
      Alipogene tiparvovec was generally well tolerated, with most adverse events being
      localized, transient, mild to moderate injection-site reactions. This article
      reviews the pharmacology of alipogene tiparvovec and its efficacy and safety in
      adults with LPLD.

PMID- 25559421
TI  - Simeprevir: a review of its use in patients with chronic hepatitis C virus
      infection.
AB  - Simeprevir (OlysioTM; GalexosTM; Sovriad(r)) is an orally-administered NS3/4A
      protease inhibitor for use in combined drug regimens against chronic hepatitis C
      virus (HCV) infection. This article reviews studies relevant to the EU simeprevir
      label. In proof-of-concept studies, simeprevir had potent antiviral activity
      against all HCV genotypes, except genotype 3. In trials in patients with chronic
      HCV genotype 1 infection, week-12 sustained virological response (SVR12) rates in
      treatment-naive patients and prior relapsers were significantly higher with
      simeprevir plus peginterferon-alpha/ribavirin (PR) [79-89 %] than with placebo
      plus PR (36-62 %). In prior partial/null responders, the SVR12 rate with
      simeprevir plus PR (54 %) was noninferior to that with telaprevir plus PR (55 %).
      Simeprevir plus PR was also efficacious in patients with HCV genotype 1/HIV-1 co
      infection. In prior null responders without severe liver fibrosis (cohort 1) and
      treatment-naive patients with severe liver fibrosis (cohort 2) treated with
      simeprevir plus sofosbuvir, the SVR12 rate for the two cohorts combined was 92 %.
      In patients with chronic HCV genotype 4 infection, the SVR12 rates with
      simeprevir plus PR were 83, 87 and 40 % in treatment-naive patients, prior
      relapsers and prior null responders, respectively. Grade 3-4 adverse event,
      serious adverse event and treatment withdrawal rates with simeprevir plus PR were
      similar to those with placebo plus PR. Skin rashes with simeprevir were mostly
      mild or moderate; serious photosensitivity reactions occur, but are rare.
      Simeprevir is efficacious and generally well tolerated in patients with chronic
      HCV genotypes 1 and 4 infection. Studies of simeprevir in interferon-free
      regimens and in other subpopulations with HCV infections will be of interest.

PMID- 25559422
TI  - Droxidopa: a review of its use in symptomatic neurogenic orthostatic hypotension.
AB  - The norepinephrine prodrug droxidopa (NORTHERATM) is approved in the US for the
      treatment of orthostatic dizziness, lightheadedness, or the 'feeling that you are
      about to black out' in adults with symptomatic neurogenic orthostatic hypotension
      associated with primary autonomic failure (e.g. Parkinson's disease, multiple
      system atrophy or pure autonomic failure), dopamine beta-hydroxylase deficiency
      or nondiabetic autonomic neuropathy. This article reviews the clinical efficacy
      and tolerability of droxidopa in symptomatic neurogenic orthostatic hypotension,
      as well as summarizing its pharmacological properties. Oral droxidopa was
      effective in the shorter-term treatment of patients with symptomatic neurogenic
      orthostatic hypotension, with improvements seen in symptoms, the impact of
      symptoms on daily activities and standing systolic blood pressure. More data are
      needed to confirm the longer-term efficacy of droxidopa. Droxidopa was generally
      well tolerated, although patients should be monitored for supine hypertension. 

PMID- 25559424
TI  - Nanometre-scale evidence for interfacial dissolution-reprecipitation control of
      silicate glass corrosion.
AB  - Silicate glasses are durable solids, and yet they are chemically unstable in
      contact with aqueous fluids-this has important implications for numerous
      industrial applications related to the corrosion resistance of glasses, or the
      biogeochemical weathering of volcanic glasses in seawater. The aqueous
      dissolution of synthetic and natural glasses results in the formation of a
      hydrated, cation-depleted near-surface alteration zone and, depending on
      alteration conditions, secondary crystalline phases on the surface. The long
      standing accepted model of glass corrosion is based on diffusion-coupled
      hydration and selective cation release, producing a surface-altered zone.
      However, using a combination of advanced atomic-resolution analytical techniques,
      our data for the first time reveal that the structural and chemical interface
      between the pristine glass and altered zone is always extremely sharp, with
      gradients in the nanometre to sub-nanometre range. These findings support a new
      corrosion mechanism, interfacial dissolution-reprecipitation. Moreover, they also
      highlight the importance of using analytical methods with very high spatial and
      mass resolution for deciphering the nanometre-scale processes controlling
      corrosion. Our findings provide evidence that interfacial dissolution
      reprecipitation may be a universal reaction mechanism that controls both silicate
      glass corrosion and mineral weathering. 

PMID- 25559425
TI  - Template-free nanosized faujasite-type zeolites.
AB  - Nanosized faujasite (FAU) crystals have great potential as catalysts or
      adsorbents to more efficiently process present and forthcoming synthetic and
      renewable feedstocks in oil refining, petrochemistry and fine chemistry. Here, we
      report the rational design of template-free nanosized FAU zeolites with
      exceptional properties, including extremely small crystallites (10-15 nm) with a
      narrow particle size distribution, high crystalline yields (above 80%), micropore
      volumes (0.30 cm(3) g(-1)) comparable to their conventional counterparts
      (micrometre-sized crystals), Si/Al ratios adjustable between 1.1 and 2.1
      (zeolites X or Y) and excellent thermal stability leading to superior catalytic
      performance in the dealkylation of a bulky molecule, 1,3,5-triisopropylbenzene,
      probing sites mostly located on the external surface of the nanosized crystals.
      Another important feature is their excellent colloidal stability, which
      facilitates a uniform dispersion on supports for applications in catalysis,
      sorption and thin-to-thick coatings. 

PMID- 25559423
TI  - Catechol-O-methyltransferase inhibitors in Parkinson's disease.
AB  - Inhibitors of catechol-O-methyltransferase (COMT) are commonly used as an adjunct
      to levodopa in patients with Parkinson's disease (PD) for the amelioration of
      wearing-off symptoms. This narrative review aims to discuss the role of COMT
      inhibitors on peripheral levodopa metabolism and continuous brain delivery of
      levodopa, and to describe their metabolic properties. Oral application of
      levodopa formulations with a dopa decarboxylase inhibitor (DDI) results in
      fluctuating levodopa plasma concentrations, predominantly due to the short half
      life of levodopa and its slowing of gastric emptying. Following transport across
      the blood-brain barrier and its metabolic conversion to dopamine, these
      peripheral 'ups and downs' of levodopa are reflected in fluctuating dopamine
      levels in the synaptic cleft between presynaptic and postsynaptic dopaminergic
      neurons of the nigrostriatal system. As a result, pulsatile postsynaptic
      dopaminergic stimulation takes place and results in the occurrence of motor
      complications, such as wearing-off and dyskinesia. More continuous plasma
      behaviour was observed after the combination of levodopa/DDI formulations with
      COMT inhibitors. These compounds also weaken a levodopa/DDI-related homocysteine
      increase, as biomarker for an impaired methylation capacity, which is involved in
      an elevated oxidative stress exposure. These findings favour the concept of
      chronic levodopa/DDI application with concomitant inhibition of COMT and
      monoamine oxidase, since deamination of dopamine via this enzyme also generates
      free radicals. This triple combination is suggested as standard levodopa
      application in patients with PD who need levodopa, if they will tolerate it. 

PMID- 25559426
TI  - A new finite element approach for near real-time simulation of light propagation
      in locally advanced head and neck tumors.
AB  - BACKGROUND AND OBJECTIVES: Several clinical studies suggest that interstitial
      photodynamic therapy (I-PDT) may benefit patients with locally advanced head and
      neck cancer (LAHNC). For I-PDT, the therapeutic light is delivered through
      optical fibers inserted into the target tumor. The complex anatomy of the head
      and neck requires careful planning of fiber insertions. Often the fibers'
      location and tumor optical properties may vary from the original plan therefore
      pretreatment planning needs near real-time updating to account for any changes.
      The purpose of this work was to develop a finite element analysis (FEA) approach
      for near real-time simulation of light propagation in LAHNC. METHODS: Our
      previously developed FEA for modeling light propagation in skin tissue was
      modified to simulate light propagation from interstitial optical fibers. The
      modified model was validated by comparing the calculations with measurements in a
      phantom mimicking tumor optical properties. We investigated the impact of mesh
      element size and growth rate on the computation time, and defined optimal
      settings for the FEA. We demonstrated how the optimized FEA can be used for
      simulating light propagation in two cases of LAHNC amenable to I-PDT, as proof-of
      concept. RESULTS: The modified FEA was in agreement with the measurements (P =
      0.0271). The optimal maximum mesh size and growth rate were 0.005-0.02 m and 2
      2.5 m/m, respectively. Using these settings the computation time for simulating
      light propagation in LAHNC was reduced from 25.9 to 3.7 minutes in one case, and
      10.1 to 4 minutes in another case. There were minor differences (1.62%, 1.13%)
      between the radiant exposures calculated with either mesh in both cases.
      CONCLUSIONS: Our FEA approach can be used to model light propagation from
      diffused optical fibers in complex heterogeneous geometries representing LAHNC.
      There is a range of maximum element size (MES) and maximum element growth rate
      (MEGR) that can be used to minimize the computation time of the FEA to 4 minutes.

PMID- 25559427
TI  - Attentional demands of perturbation evoked compensatory stepping responses:
      examining cognitive-motor interference to large magnitude forward perturbations.
AB  - The authors examined the cognitive-motor interference of reactive balance control
      under dual-task condition in young healthy adults. Sudden large forward
      perturbations were delivered in stance position with (dual-task) and without
      (single-task balance) a working memory task. This task was also performed in
      quiet stance (single-task cognition). Dual tasking significantly reduced postural
      stability and compensatory step length, and delayed the reaction time. The
      significant linear correlation between postural stability and compensatory step
      length present in the single-task balance condition was absent in the dual-task
      condition. Performance on the cognitive task also declined under the dual-task
      condition. Our results indicate a mutual cognitive-motor interference between the
      reactive balance and the working memory task suggesting a potential overlap
      between attentional resources allocated for these two tasks. 

PMID- 25559428
TI  - Fragment-based drug discovery of 2-thiazolidinones as BRD4 inhibitors: 2.
      Structure-based optimization.
AB  - The signal transduction of acetylated histone can be processed through a
      recognition module, bromodomain. Several inhibitors targeting BRD4, one of the
      bromodomain members, are in clinical trials as anticancer drugs. Hereby, we
      report our efforts on discovery and optimization of a new series of 2
      thiazolidinones as BRD4 inhibitors along our previous study. In this work, guided
      by crystal structure analysis, we reversed the sulfonamide group and identified a
      new binding mode. A structure-activity relationship study on this new series led
      to several potent BRD4 inhibitors with IC50 of about 0.05-0.1 MUM in FP binding
      assay and GI50 of 0.1-0.3 MUM in cell based assays. To complete the lead-like
      assessment of this series, we further checked its effects on BRD4 downstream
      protein c-Myc, investigated its selectivity among five different bromodomain
      proteins, as well as the metabolic stability test, and reinforced the utility of
      2-thiazolidinone scaffold as BET bromodomain inhibitors in novel anticancer drug
      development. 

PMID- 25559429
TI  - The WATCHMAN device for stroke prophylaxis in atrial fibrillation: an evolving
      niche.
AB  - Atrial fibrillation is associated with a markedly increased risk of
      thromboembolic stroke. At present, lifelong antithrombotic therapy with warfarin
      or a novel oral anticoagulant is indicated for prophylaxis in the majority of
      patients. Left atrial appendage occlusion devices have been developed as an
      alternative to these agents, aiming to avoid issues around consistency of
      anticoagulation, bleeding risk, and drug-related side effects. The best evidence
      is available for Boston Scientific's WATCHMAN device. The safety and efficacy of
      WATCHMAN and other similar devices have been questioned, although the increasing
      body of evidence supports a role in selected settings. A recently updated
      randomized controlled trial of WATCHMAN (WATCHMAN Left Atrial Appendage System
      for Embolic PROTECTion in Patients with Atrial Fibrillation [PROTECT-AF])
      demonstrates its noninferiority to warfarin and suggests an advantage in terms of
      functional outcome for patients, with superior net clinical benefit 6 to 9 months
      after starting treatment. The procedural risk associated with device implantation
      remains substantial, although improving device design and increasing operator
      experience means that this should decrease in the future. As the body of data and
      overall experience around WATCHMAN grow, it may come to be recognized as the best
      option in selected patients.

PMID- 25559430
TI  - Linear array ultrasound in low-grade glioma surgery: histology-based assessment
      of accuracy in comparison to conventional intraoperative ultrasound and
      intraoperative MRI.
AB  - INTRODUCTION: In low-grade glioma (LGG) surgery, intraoperative differentiation
      between tumor and most likely tumor-free brain tissue can be challenging.
      Intraoperative ultrasound can facilitate tumor resection. The aim of this study
      is to evaluate the accuracy of linear array ultrasound in comparison to
      conventional intraoperative ultrasound (cioUS) and intraoperative high-field MRI
      (iMRI). METHODS: We prospectively enrolled 13 patients harboring a LGG of WHO
      Grade II. After assumed near total removal, a resection control was performed
      using navigated cioUS, navigated lioUS, and iMRI. We harvested 30 navigated
      biopsies from the resection cavity and compared the histopathological findings
      with the respective imaging results. Spearman's rho was calculated to test for
      significant correlations. Sensitivity and specificity as well as receiver
      operating characteristics (ROC) were calculated to assess test performance of
      each imaging modality. RESULTS: Imaging results of lioUS correlated significantly
      (p < 0.009) with iMRI. Both iMRI and lioUS correlated significantly with final
      histopathological diagnosis (p < 0.006, p < 0.014). cioUS did not correlate with
      other imaging findings or with final diagnosis. The highest sensitivity for
      residual tumor detection was found in iMRI (83 %), followed by lioUS (79 %). The
      sensitivity of cioUS was only 21 %. Specificity was highest in cioUS (100 %),
      whereas iMRI and lioUS both achieved 67 %. ROC curves showed fair results for
      iMRI and lioUS and a poor result for cioUS. CONCLUSIONS: Intraoperative resection
      control in LGGs using lioUS reaches a degree of accuracy close to iMRI. Test
      results of lioUS are superior to cioUS. cioUS often fails to discriminate solid
      tumors from "normal" brain tissue during resection control. Only in lesions <10
      cc cioUS does show good accuracy.

PMID- 25559431
TI  - Predictors of internalised HIV-related stigma: a systematic review of studies in
      sub-Saharan Africa.
AB  - This systematic review aims to synthesise evidence on predictors of internalised
      HIV stigma amongst people living with HIV in sub-Saharan Africa. Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used.
      Studies were identified through electronic databases, grey literature, reference
      harvesting and contacts with key researchers. Quality of findings was assessed
      through an adapted version of the Cambridge Quality Checklists. A total of 590
      potentially relevant titles were identified. Seventeen peer-reviewed articles and
      one draft book chapter were included. Studies investigated socio-demographic, HIV
      related, intra-personal and interpersonal correlates of internalised stigma.
      Eleven articles used cross-sectional data, six articles used prospective cohort
      data and one used both prospective cohort and cross-sectional data to assess
      correlates of internalised stigma. Poor HIV-related health weakly predicted
      increases in internalised HIV stigma in three longitudinal studies. Lower
      depression scores and improvements in overall mental health predicted reductions
      in internalised HIV stigma in two longitudinal studies, with moderate and weak
      effects, respectively. No other consistent predictors were found. Studies
      utilising analysis of change and accounting for confounding factors are necessary
      to guide policy and programming but are scarce. High-risk populations, other
      stigma markers that might layer upon internalised stigma, and structural drivers
      of internalised stigma need to be examined. 

PMID- 25559432
TI  - Utilization of antibiotics for methicillin-resistant Staphylococcus aureus
      infection in cystic fibrosis.
AB  - OBJECTIVES: The purpose of this study was to characterize the utilization of
      antibiotics for chronic methicillin-resistant Staphylococcus aureus (MRSA)
      infection in cystic fibrosis (CF) patients with acute pulmonary exacerbations
      (PEx). METHODS: An anonymous national cross-sectional survey of CF Foundation
      accredited care programs was performed using an electronic survey tool. RESULTS:
      Fifty-eight percent (152/261) CF Foundation accredited programs completed the
      survey. Ninety-eight percent (149/152) of respondents reported using antibiotics
      (oral or intravenous) against MRSA. Variability exists in the use of antibiotics
      amongst the programs and in the dosages utilized. For oral outpatient treatment,
      sulfamethoxazole/trimethoprim was the most commonly utilized antibiotic by both
      pediatric (109/287, 38%) and adult (99/295, 34%) respondents, of which, ten
      percent of reported to use it in combination with rifampin. For inpatient
      treatment, linezolid (both intravenous (IV) and oral) was most commonly utilized
      in both pediatric (IV 35/224, 16%; oral 41/224, 18%), and adult (IV 44/235, 19%;
      oral 38/235, 16%) respondents for inpatient treatment. IV vancomycin was the
      second most commonly utilized antibiotic by pediatric (70/224, 31%) and adult
      (71/235, 30%) respondents. Most respondents reported dose titration to achieve a
      vancomycin trough level of 15-20 mg/L (150/179, 84%). Topical or inhaled
      antibiotic utilization was reported to be an uncommon practice with approximately
      70% of pediatric and adult respondents reporting to use them either rarely or
      never. The concomitant use of anti-MRSA and anti-pseudomonal antibiotics was
      common with 96% of pediatric and 99% of adult respondents answering in the
      affirmative. CONCLUSION: We conclude that anti-MRSA antibiotics are utilized via
      various dosage regimens by a majority of CF Foundation accredited care programs
      for the treatment of chronic MRSA in PEx, and there is no consensus on the best
      treatment approach.

PMID- 25559433
TI  - A new statistical approach to combining p-values using gamma distribution and its
      application to genome-wide association study.
AB  - BACKGROUND: Combining information from different studies is an important and
      useful practice in bioinformatics, including genome-wide association study, rare
      variant data analysis and other set-based analyses. Many statistical methods have
      been proposed to combine p-values from independent studies. However, it is known
      that there is no uniformly most powerful test under all conditions; therefore,
      finding a powerful test in specific situation is important and desirable.
      RESULTS: In this paper, we propose a new statistical approach to combining p
      values based on gamma distribution, which uses the inverse of the p-value as the
      shape parameter in the gamma distribution. CONCLUSIONS: Simulation study and real
      data application demonstrate that the proposed method has good performance under
      some situations.

PMID- 25559434
TI  - Graphene-supported nickel-platinum nanoparticles as efficient catalyst for
      hydrogen generation from hydrous hydrazine at room temperature.
AB  - Ultrafine monodisperse bimetallic NiPt nanoparticles with different compositions
      have been successfully synthesized by coreduction of nickel acetylacetonate and
      platinum acetylacetonate with borane-tert-butylamine in oleylamine. Among all the
      catalysts tested, Ni84Pt16/graphene exhibited 100% hydrogen selectivity, and
      marked high catalytic activity, with TOF values of 415 h(-1) at 50  degrees C,
      and 133 h(-1) at 25  degrees C for hydrogen generation from alkaline solution of
      hydrazine. 

PMID- 25559435
TI  - Demography and treatment response in patients with predominant non-erosive reflux
      disease or functional dyspepsia.
AB  - BACKGROUND AND AIM: Non-erosive reflux disease (NERD) and functional dyspepsia
      (FD) share some common features, and the appropriateness of managing these
      diseases independently has been questioned. A post-hoc subgroup analysis of the
      LEGEND study was performed to compare demographics and treatment response between
      patients with NERD and patients with FD. METHODS: Patients with reflux and
      dyspepsia symptoms who had no endoscopic evidence of mucosal breaks and/or
      erosions were included and divided into groups with predominant NERD (n = 1546)
      or FD (n = 614). Patients received lansoprazole for 4 weeks, and their symptoms
      were evaluated using questionnaires. RESULTS: FD patients were significantly
      younger than NERD patients (54 vs 60 years), more likely to have a body mass
      index < 25 kg/m(2) (72.4% vs 67.1%), less likely to have a hiatal hernia (24.0%
      vs 31.2%), and more likely to feel continuous stress (54.7% vs 48.0%). After 4
      weeks of treatment, > 60% of both patients reported an improvement in reflux
      symptoms and in most dyspepsia symptoms. The improvement rate for reflux symptoms
      was lower in FD patients than in NERD patients (P < 0.05), whereas the
      improvement rate for dyspepsia symptoms did not differ between patient groups.
      CONCLUSION: Although no clinically significant differences in pathophysiology
      exist between NERD and FD, there are some between-group differences in
      demographic characteristics and improvement rates for reflux symptoms after
      treatment with lansoprazole. It remains to be discussed whether it is necessary
      to make a strict differential diagnosis between these two conditions.

PMID- 25559436
TI  - Prehospital aspirin use is associated with reduced risk of acute respiratory
      distress syndrome in critically ill patients: a propensity-adjusted analysis.
AB  - OBJECTIVES: Platelet activation plays an active role in the pathogenesis of acute
      respiratory distress syndrome. In our prior study of 575 patients at high risk
      for acute respiratory distress syndrome, concurrent statin and aspirin use was
      associated with reduced acute respiratory distress syndrome. However, the largest
      study (n = 3,855) to date found no significant benefit of prehospital aspirin in
      a lower-risk population when adjusted for the propensity for aspirin use. We
      aimed to determine whether prehospital aspirin use is associated with decreased
      acute respiratory distress syndrome in patients at high risk for acute
      respiratory distress syndrome after adjusting for the propensity to receive
      aspirin. DESIGN: Secondary analysis of patients enrolled prospectively in the
      Validating Acute Lung Injury Markers for Diagnosis study. PATIENTS: A total of
      1,149 critically ill patients (>=40 years old) admitted to the medical or
      surgical ICUs of an academic tertiary care hospital including 575 previously
      reported patients as well as additional patients who were enrolled after
      completion of the prior statin and aspirin study. INTERVENTION: None.
      MEASUREMENTS AND RESULTS: Of 1,149 patients, 368 (32%) developed acute
      respiratory distress syndrome during the first 4 ICU days and 287 (25%) patients
      had prehospital aspirin use. Patients with prehospital aspirin had significantly
      lower prevalence of acute respiratory distress syndrome (27% vs 34%; p=0.034). In
      a multivariable, propensity-adjusted analysis including age, gender, race,
      sepsis, and Acute Physiology and Chronic Health Evaluation score II, prehospital
      aspirin use was associated with a decreased risk of acute respiratory distress
      syndrome (odds ratio, 0.66; 95% CI, 0.46-0.94) in the entire cohort and in a
      subgroup of 725 patients with sepsis (odds ratio, 0.60; 95% CI, 0.41-0.90).
      CONCLUSIONS: In this selected cohort of critically ill patients, prehospital
      aspirin use was independently associated with a decreased risk of acute
      respiratory distress syndrome even after adjusting for the propensity of
      prehospital aspirin use. These findings support the need for prospective clinical
      trials to determine whether aspirin may be beneficial for the prevention of
      clinical acute respiratory distress syndrome.

PMID- 25559437
TI  - Ultrasound for the assessment of peripheral skeletal muscle architecture in
      critical illness: a systematic review.
AB  - OBJECTIVES: To critically evaluate and summarize identified evidence for the use
      of ultrasound to measure peripheral skeletal muscle architecture during critical
      illness. DATA SOURCES: Seven electronic databases (Medline, Cumulative Index to
      Nursing and Allied Health Literature, Cochrane Library, Physiotherapy Evidence
      Database, Scopus, Excerpta Medica Database, and Web of Science [including Science
      Citations and Conference Proceedings]) and personal libraries were searched for
      relevant articles. Cross-referencing further identified references. STUDY
      SELECTION: Quantitative study designs excluding abstracts, published in English,
      including adult critically ill patients in the ICU, evaluating peripheral
      skeletal muscle architecture during critical illness with ultrasound were
      included. Studies using ultrasonographic muscle data as outcome measures in
      interventional trials were excluded. DATA EXTRACTION: Performed by one reviewer
      using a standardized data extraction form and cross-checked by a second reviewer.
      Quality appraisal was undertaken by two independent reviewers-studies were
      classified, graded, and appraised according to standardized algorithms and
      checklists. Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines were adhered to. DATA SYNTHESIS: Seven studies with independent
      patient cohorts totaling 300 participants were included. One study adopted a case
      control design, and the remainder were case series. Ultrasound data demonstrated
      deficits in a variety of peripheral skeletal muscle architecture variables across
      a range of muscle groups associated with critical illness. Ultrasound offered
      more accurate data compared to limb circumference measurement and has excellent
      reported reliability, but underestimated data acquired via more invasive muscle
      biopsy. CONCLUSION: Ultrasound provides clinical utility for assessing the
      trajectory of change in peripheral skeletal muscle architecture during critical
      illness, supplementing more detailed characterization, albeit rarely used, from
      muscle biopsy analysis. Adoption of standardized operating protocols for
      measurement will facilitate future meta-analysis of data.

PMID- 25559439
TI  - Differences in vital signs between elderly and nonelderly patients prior to ward
      cardiac arrest.
AB  - OBJECTIVES: Vital signs and composite scores, such as the Modified Early Warning
      Score, are used to identify high-risk ward patients and trigger rapid response
      teams. Although age-related vital sign changes are known to occur, little is
      known about the differences in vital signs between elderly and nonelderly
      patients prior to ward cardiac arrest. We aimed to compare the accuracy of vital
      signs for detecting cardiac arrest between elderly and nonelderly patients.
      DESIGN: Observational cohort study. SETTING: Five hospitals in the United States.
      PATIENTS: A total of 269,956 patient admissions to the wards with documented age,
      including 422 index ward cardiac arrests. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Patient characteristics and vital signs prior to cardiac arrest
      were compared between elderly (age, 65 yr or older) and nonelderly (age, <65 yr)
      patients. The area under the receiver operating characteristic curve for vital
      signs and the Modified Early Warning Score were also compared. Elderly patients
      had a higher cardiac arrest rate (2.2 vs 1.0 per 1,000 ward admissions; p<0.001)
      and in-hospital mortality (2.9% vs 0.7%; p<0.001) than nonelderly patients.
      Within 4 hours of cardiac arrest, elderly patients had significantly lower mean
      heart rate (88 vs 99 beats/min; p<0.001), diastolic blood pressure (60 vs 66 mm
      Hg; p=0.007), shock index (0.82 vs 0.93; p<0.001), and Modified Early Warning
      Score (2.6 vs 3.3; p<0.001) and higher pulse pressure index (0.45 vs 0.41;
      p<0.001) and temperature (36.4 degrees C vs 36.3 degrees C; p=0.047). The area
      under the receiver operating characteristic curves for all vital signs and the
      Modified Early Warning Score were higher for nonelderly patients than elderly
      patients (Modified Early Warning Score area under the receiver operating
      characteristic curve 0.85 [95% CI, 0.82-0.88] vs 0.71 [95% CI, 0.68-0.75];
      p<0.001). CONCLUSIONS: Vital signs more accurately detect cardiac arrest in
      nonelderly patients compared with elderly patients, which has important
      implications for how they are used for identifying critically ill patients. More
      accurate methods for risk stratification of elderly patients are necessary to
      decrease the occurrence of this devastating event.

PMID- 25559438
TI  - Morbidity and survival probability in burn patients in modern burn care.
AB  - OBJECTIVE: Characterizing burn sizes that are associated with an increased risk
      of mortality and morbidity is critical because it would allow identifying
      patients who might derive the greatest benefit from individualized, experimental,
      or innovative therapies. Although scores have been established to predict
      mortality, few data addressing other outcomes exist. The objective of this study
      was to determine burn sizes that are associated with increased mortality and
      morbidity after burn. DESIGN AND PATIENTS: Burn patients were prospectively
      enrolled as part of the multicenter prospective cohort study, Inflammation and
      the Host Response to Injury Glue Grant, with the following inclusion criteria: 0
      99 years old, admission within 96 hours after injury, and more than 20% total
      body surface area burns requiring at least one surgical intervention. SETTING:
      Six major burn centers in North America. MEASUREMENTS AND MAIN RESULTS: Burn size
      cutoff values were determined for mortality, burn wound infection (at least two
      infections), sepsis (as defined by American Burn Association sepsis criteria),
      pneumonia, acute respiratory distress syndrome, and multiple organ failure
      (Denver 2 score>3) for both children (<16 yr) and adults (16-65 yr). Five hundred
      seventy-three patients were enrolled, of which 226 patients were children. Twenty
      three patients were older than 65 years and were excluded from the cutoff
      analysis. In children, the cutoff burn size for mortality, sepsis, infection, and
      multiple organ failure was approximately 60% total body surface area burned. In
      adults, the cutoff for these outcomes was lower, at approximately 40% total body
      surface area burned. CONCLUSIONS: In the modern burn care setting, adults with
      over 40% total body surface area burned and children with over 60% total body
      surface area burned are at high risk for morbidity and mortality, even in highly
      specialized centers.

PMID- 25559440
TI  - Activity descriptor identification for oxygen reduction on platinum-based
      bimetallic nanoparticles: in situ observation of the linear composition-strain
      activity relationship.
AB  - Despite recent progress in developing active and durable oxygen reduction
      catalysts with reduced Pt content, lack of elegant bottom-up synthesis procedures
      with knowledge over the control of atomic arrangement and morphology of the Pt
      alloy catalysts still hinders fuel cell commercialization. To follow a less
      empirical synthesis path for improved Pt-based catalysts, it is essential to
      correlate catalytic performance to properties that can be easily controlled and
      measured experimentally. Herein, using Pt-Co alloy nanoparticles (NPs) with
      varying atomic composition as an example, we show that the atomic distribution of
      Pt-based bimetallic NPs under operating conditions is strongly dependent on the
      initial atomic ratio by employing microscopic and in situ spectroscopic
      techniques. The PtxCo/C NPs with high Co content possess a Co concentration
      gradient such that Co is concentrated in the core and gradually depletes in the
      near-surface region, whereas the PtxCo/C NPs with low Co content possess a
      relatively uniform distribution of Co with low Co population in the near-surface
      region. Despite their different atomic structure, the oxygen reduction reaction
      (ORR) activity of PtxCo/C and Pt/C NPs is linearly related to the bulk average Pt
      Pt bond length (RPt-Pt). The RPt-Pt is further shown to contract linearly with
      the increase in Co/Pt composition. These linear correlations together demonstrate
      that (i) the improved ORR activity of PtxCo/C NPs over pure Pt NPs originates
      predominantly from the compressive strain and (ii) the RPt-Pt is a valid strain
      descriptor that bridges the activity and atomic composition of Pt-based
      bimetallic NPs. 

PMID- 25559441
TI  - Rational design of viscosity reducing mutants of a monoclonal antibody:
      hydrophobic versus electrostatic inter-molecular interactions.
AB  - High viscosity of monoclonal antibody formulations at concentrations >=100 mg/mL
      can impede their development as products suitable for subcutaneous delivery. The
      effects of hydrophobic and electrostatic intermolecular interactions on the
      solution behavior of MAB 1, which becomes unacceptably viscous at high
      concentrations, was studied by testing 5 single point mutants. The mutations were
      designed to reduce viscosity by disrupting either an aggregation prone region
      (APR), which also participates in 2 hydrophobic surface patches, or a negatively
      charged surface patch in the variable region. The disruption of an APR that lies
      at the interface of light and heavy chain variable domains, VH and VL, via L45K
      mutation destabilized MAB 1 and abolished antigen binding. However, mutation at
      the preceding residue (V44K), which also lies in the same APR, increased apparent
      solubility and reduced viscosity of MAB 1 without sacrificing antigen binding or
      thermal stability. Neutralizing the negatively charged surface patch (E59Y) also
      increased apparent solubility and reduced viscosity of MAB 1, but charge reversal
      at the same position (E59K/R) caused destabilization, decreased solubility and
      led to difficulties in sample manipulation that precluded their viscosity
      measurements at high concentrations. Both V44K and E59Y mutations showed similar
      increase in apparent solubility. However, the viscosity profile of E59Y was
      considerably better than that of the V44K, providing evidence that inter
      molecular interactions in MAB 1 are electrostatically driven. In conclusion,
      neutralizing negatively charged surface patches may be more beneficial toward
      reducing viscosity of highly concentrated antibody solutions than charge reversal
      or aggregation prone motif disruption.

PMID- 25559442
TI  - Transcriptome analysis of canine cardiac fat pads: involvement of two novel long
      non-coding RNAs in atrial fibrillation neural remodeling.
AB  - Intrinsic cardiac autonomic neural remodeling (ANR) has been reported to be
      involved in the initiation and maintenance of atrial fibrillation (AF). Long non
      coding RNAs (lncRNAs) are important orchestrators of gene regulatory networks.
      However, little is known about the relationships between lncRNAs and cardiac ANR
      in AF. In this study, second-generation RNA sequencing was performed to examine
      the transcriptomes of lncRNAs in AF and non-AF canine cardiac fat pads. A total
      of 61,616 putative lncRNAs were yielded, in which 166 were downregulated and 410
      were upregulated with more than twofold change. Bioinformatics analysis showed
      that the aberrantly expressed genes were associated with neural development,
      migration and neurodegenerative disorders. On the basis of a series of filtering
      pipelines, two new lncRNAs, namely, TCONS_00032546 and TCONS_00026102, were
      selected. Silencing of TCONS_00032546 or TCONS_00026102 with lentiviruses in vivo
      could significantly shorten or prolong the atrial effective refractory period
      thereby increasing or preventing AF inducibility by promoting or inhibiting the
      neurogenesis. Besides, the expression of CCND1-FGF19-FGF4-FGF3 gene cluster and
      SLC25A4, the nearby genes of TCONS_00032546 and TCONS_00026102, were negatively
      correlated with that of lncRNAs. Furthermore, combining bioinformatics analysis
      with literature review, TCONS_00032546 and TCONS_00026102 may induce effects by
      increasing the CCND1-FGF19-FGF3-FGF4 gene cluster and SLC25A4 via complex
      mechanisms during neural remodeling. Taken together, dysregulated lncRNAs may
      play regulatory roles in AF neural remodeling, which may further provide
      potential therapeutic targets for prophylaxis and treatment of AF.

PMID- 25559445
TI  - Fatty acid binding protein FABP3 from Chinese mitten crab Eriocheir sinensis
      participates in antimicrobial responses.
AB  - Intracellular fatty acid-binding proteins (FABPs) are members of the lipid
      binding protein superfamily. Aside from the main functions of FABPs in the uptake
      and transport of fatty acids, they are also critical in innate immunology. In
      this work, the full-length cDNA for a Chinese mitten crab Eriocheir sinensis FABP
      (Es-FABP3) was cloned with an open reading frame of 402 bp encoding a 133 amino
      acid polypeptide. Analysis using quantitative real-time PCR (qPCR) revealed that
      Es-FABP3 transcripts were widely distributed in gills, muscle, intestine,
      hepatopancreas, eyestalk, heart, stomach, brain, thoracic ganglia and hemocytes.
      After challenge with pathogen associated molecular pattern molecules (PAMPs), the
      relative mRNA expression levels of Es-FABP3 increased in hepatopancreas, gills
      and hemocytes. Moreover, the mature recombinant Es-FABP3 protein exhibited
      different binding activities to bacteria and fungus and inhibited the growth of
      different microbes. These collective results demonstrated the role of Es-FABP3 in
      the immunoreactions of E. sinensis to PAMPs.

PMID- 25559444
TI  - Predictors of poor adherence among people on antiretroviral treatment in Cape
      Town, South Africa: a case-control study.
AB  - A case-control study was conducted to describe the frequency with which
      structural- and individual-level barriers to adherence are experienced by people
      receiving antiretroviral (ARV) treatment and to determine predictors of non
      adherence. Three hundred adherent and 300 non-adherent patients from 6 clinics in
      Cape Town completed the LifeWindows Information-Motivation-Behavioral Skills ART
      Adherence Questionnaire, the Substance Abuse and Mental Illness Symptoms Screener
      and the Structural Barriers to Clinic Attendance (SBCA) and Medication-taking
      (SBMT) scales. Overall, information-related barriers were reported most
      frequently followed by motivation and behaviour skill defects. Structural
      barriers were reported least frequently. Logistic regression analyses revealed
      that gender, behaviour skill deficit scores, SBCA scores and SBMT scores
      predicted non-adherence. Despite the experience of structural barriers being
      reported least frequently, structural barriers to medication-taking had the
      greatest impact on adherence (OR: 2.32, 95% CI: 1.73 to 3.12), followed by
      structural barriers to clinic attendance (OR: 2.06, 95% CI: 1.58 to 2.69) and
      behaviour skill deficits (OR: 1.34, 95% CI: 1.05 to 1.71). Our data indicate the
      need for policy directed at the creation of a health-enabling environment that
      would enhance the likelihood of adherence among antiretroviral therapy users.
      Specifically, patient empowerment strategies aimed at increasing treatment
      literacy and management skills should be strengthened. Attempts to reduce
      structural barriers to antiretroviral treatment adherence should be expanded to
      include increased access to mental health care services and nutrition support. 

PMID- 25559446
TI  - A C-type lectin (LvCTL4) from Litopenaeus vannamei is a downstream molecule of
      the NF-kappaB signaling pathway and participates in antibacterial immune
      response.
AB  - C-type lectins (CTLs) play multiple roles in innate immune defense against
      invading pathogens in both vertebrates and invertebrates. In this study, a new C
      type lectin gene from pacific white shrimp Litopenaeus vannamei (designated as
      LvCTL4) was cloned by rapid amplification of the cDNA ends (RACE) method. The
      full-length cDNA of LvCTL4 was 563 bp with open reading frame (ORF) of 471 bp
      encoding a polypeptide of 156 amino acids, including a putative signal sequence
      and a single C-type lectin-like domain (CTLD). The CTLD of 137 amino acid
      residues contained a mutated 'EPA' (Glu(121)-Pro(122)-Ala(123)) motif in the
      calcium-binding site 2 and three conserved disulfide bonds involved in structure
      maintenance. Tissue expression analysis showed LvCTL4 was ubiquitously
      distributed with high levels in gill, intestine, epithelium and hepatopancreas.
      The expression of LvCTL4 in gill was up-regulated in response to Vibrio
      parahaemolyticus challenge. RNAi knock-down of the LvCTL4 gene significantly
      increased mortality after V. parahaemolyticus infection. A 103 bp 5' flanking
      promoter sequence was obtained using the genome walking method and it contained a
      conserved NF-kappaB binding motif. Dual-Luciferase assay showed both LvDorsal and
      LvRelish could up regulate the promoter activity of LvCTL4. This is the first
      report that a shrimp C-type lectin can be regulated by both LvDorsal and
      LvRelish. These findings provided novel insights into the regulation of shrimp
      CTLs expression.

PMID- 25559447
TI  - Scanning Electron Microscopic Studies on the Gills of the Catfish Heteropneustes
      fossilis (Bloch) Exposed to Copper at Varying pH.
AB  - Alterations in gill ultra-structure of the catfish, Heteropneustes fossilis
      exposed to copper at varying pH were investigated using scanning electron
      microscopy. Fish were treated with 3 ppm copper sulphate (48 h LC50 concentration
      at pH 7 +/- 0.5) at varying pH of diluent water. Low pH resulted in higher copper
      (30.01 ug/g dry wt.) accumulation on gills as compared to neutral and high pH
      treatments, at 18.01 and 16.07 ug/g respectively. Post (48 h) exposure
      observations included lesions in gills of the treated fish, epithelial lifting,
      loss of alignment of primary and secondary lamellae, hyperplasia, and hypertrophy
      of the respiratory epithelium. Fish at pH 5 +/- 0.5 showed relatively greater
      injury compared to pH 8 +/- 0.5. The severity of gill damage in copper treated
      fish followed the sequence of pH 5 +/- 0.5 > pH 7 +/- 0.5 > pH 8 +/- 0.5. Results
      indicate the synergistic stress caused in fish gill due to acute toxicity of
      copper and low pH. 

PMID- 25559448
TI  - A comprehensive high-resolution mass spectrometry approach for characterization
      of metabolites by combination of ambient ionization, chromatography and imaging
      methods.
AB  - RATIONALE: An ideal method for bioanalytical applications would deliver spatially
      resolved quantitative information in real time and without sample preparation. In
      reality these requirements can typically not be met by a single analytical
      technique. Therefore, we combine different mass spectrometry approaches:
      chromatographic separation, ambient ionization and imaging techniques, in order
      to obtain comprehensive information about metabolites in complex biological
      samples. METHODS: Samples were analyzed by laser desorption followed by
      electrospray ionization (LD-ESI) as an ambient ionization technique, by matrix
      assisted laser desorption/ionization (MALDI) mass spectrometry imaging for
      spatial distribution analysis and by high-performance liquid
      chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) for
      quantitation and validation of compound identification. All MS data were acquired
      with high mass resolution and accurate mass (using orbital trapping and ion
      cyclotron resonance mass spectrometers). Grape berries were analyzed and
      evaluated in detail, whereas wheat seeds and mouse brain tissue were analyzed in
      proof-of-concept experiments. RESULTS: In situ measurements by LD-ESI without any
      sample preparation allowed for fast screening of plant metabolites on the grape
      surface. MALDI imaging of grape cross sections at 20 um pixel size revealed the
      detailed distribution of metabolites which were in accordance with their
      biological function. HPLC/ESI-MS was used to quantify 13 anthocyanin species as
      well as to separate and identify isomeric compounds. A total of 41 metabolites
      (amino acids, carbohydrates, anthocyanins) were identified with all three
      approaches. Mass accuracy for all MS measurements was better than 2 ppm (root
      mean square error). CONCLUSIONS: The combined approach provides fast screening
      capabilities, spatial distribution information and the possibility to quantify
      metabolites. Accurate mass measurements proved to be critical in order to
      reliably combine data from different MS techniques. Initial results on the
      mycotoxin deoxynivalenol (DON) in wheat seed and phospholipids in mouse brain as
      a model for mammalian tissue indicate a broad applicability of the presented
      workflow.

PMID- 25559449
TI  - Ultrahigh-performance liquid chromatography/tandem mass spectrometry method for
      evaluating enzyme activity and screening inhibitors of cyclooxygenase-2.
AB  - RATIONALE: Prostaglandin E2 is an important biomarker in many biological systems.
      The development of sensitive and reliable analytical methods for monitoring PGE2
      contents in various samples is of great interest. Here we developed an improved
      method for evaluating the enzyme activity and screening COX-2 inhibitors using
      ultrahigh-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS)
      combined with PGE2 derivatization. METHODS: Girard's reagent-T was used as the
      derivatization reagent and the reaction conditions were optimized. The
      established method was performed to screen the COX-2 inhibitors from effective
      constituents of herbs and detect the concentration of PGE2 in biological tissue
      samples (liver and kidney). The IC50 values of celecoxib, rofecoxib, sinomenine,
      bulleyaconitine A, tetrandrine, fangchinoline, berberine hydrochloride and
      sophocarpidine towards COX-2 were determined. RESULTS: This method improves the
      quantitative ability for PGE2 , including the linearly dependent coefficient,
      linearity range and limit of detection. After derivatization, the derivatized
      PGE2 could be detected in positive ion mode of electrospray ionization (ESI),
      which improves the detection sensitivity 10-fold compared to that of the direct
      detection of underivatized PGE2 in negative ESI mode. Besides the positive
      control, sinomenine (IC50 =113 MUM) and bulleyaconitine A (IC50=53 MUM) were
      found to be potent COX-2 inhibitors. CONCLUSIONS: All the results indicate that
      the present derivatization quantification method of PGE2 could be used as the
      detection method of COX-2 enzyme activity and as the screening method for COX-2
      inhibitors.

PMID- 25559450
TI  - Tandem mass spectrometric characterization of acetylated polyhydroxy
      hellebosaponins, the principal steroid saponins in Helleborus niger L. roots(#).
AB  - RATIONALE: Isolation and extensive nuclear magnetic resonance (NMR) analyses
      revealed polyhydroxy steroid saponins to be characteristic constituents in
      Helleborus niger L. roots. A comprehensive study including various multi-stage
      mass spectrometry (MS(n) ) experiments provided first solid chromatographic and
      mass spectrometric information facilitating future analysis and structural
      assessment of polyhydroxy saponins by LC/MS(n) techniques without isolation and
      NMR analyses. METHODS: The polyhydroxy saponins were analyzed by direct syringe
      injection or chromatographically separated on a capillary high-performance liquid
      chromatography (HPLC) system coupled to an electrospray ionization (ESI) source.
      MS(n) spectra were recorded on an ion trap mass spectrometer including up to four
      fragmentation stages (LC/ESI-MS/MS). Additionally, high-resolution mass spectra
      were recorded on an Orbitrap Fourier transform (FT) mass spectrometer equipped
      with a nanospray-ESI interface. RESULTS: The polyhydroxy hellebosaponins A and D
      were discovered to be significant constituents from H. niger roots. Extensive
      study of their MS(n) data revealed that they readily fragmented in the positive
      ion mode providing diagnostic fragments for elucidation of the steroidal
      character and number of OH groups. The negative ion mode yielded valuable
      information on the [M-H](-) ion, number and location of acetyl groups and sugar
      units. Additionally, fragmentation pathways for positive and negative ion modes
      were proposed. CONCLUSIONS: These results not only extend the knowledge about H.
      niger saponins, but also provide a facilitated approach to the analysis of
      polyhydroxy saponins by LC/MS(n) without prior isolation and extensive NMR
      identification. Additionally, proposed fragmentation pathways for positive and
      negative ionization modes provide a solid complementary database for further,
      more detailed MS(n) studies.

PMID- 25559451
TI  - Mass accuracy improvement of reversed-phase liquid chromatography/electrospray
      ionization mass spectrometry based urinary metabolomic analysis by post-run
      calibration using sodium formate cluster ions.
AB  - RATIONALE: Typically, a batch metabolomics analysis using liquid
      chromatography/electrospray ionization time-of-flight mass spectrometry (LC/ESI
      TOF MS) takes 2 to 3 days. However, the mass accuracy - which has an important
      influence on metabolite identification - can drift by as much as about 17 ppm in
      such a time period. In an untargeted urinary metabolomics analysis by reversed
      phase liquid chromatography (RPLC)/ESI-MS, the signals of sodium formate cluster
      ions were detected at the column-washing step. The cluster ions were used to
      calibrate the mass spectrometer for more accurate detection. METHODS: The spectra
      were calibrated post-run by the sodium formate cluster ions, which were used as
      the internal standard, in order to improve the mass accuracy. RESULTS: In the
      analysis of urine samples, we calibrated the spectra acquired by the micrOTOF
      with the sodium cluster ions. In positive mode ESI, the average errors of these
      cluster ions were improved to +/-0.48 ppm and in negative mode ESI, to +/-0.94
      ppm after calibration. The mass accuracy remained within +/-0.01 ppm over the
      duration of 6.25 days. An error window of 4 ppm appears to be suitable for
      metabolite identification when using post-calibration. CONCLUSIONS: The results
      showed that sodium formate cluster ions could be utilized for the calibration of
      LC/ESI-TOF MS and the average instrumental errors could be maintained at low
      levels for long-term analyses. This method could be applied not only to urine
      sample, but also to low sodium samples, such as saliva, by dissolving the sample
      in 1 MUM sodium formate solution. This method provides a good solution for
      accurate mass detection of metabolomic analysis.

PMID- 25559452
TI  - Evaluation of commercially available reagents as a reference material for
      intramolecular carbon isotopic measurements of acetic acid.
AB  - RATIONALE: Recent advances in analytical techniques for the intramolecular carbon
      isotopic ratio measurement of some organic compounds have provided important
      information on carbon cycles in biochemistry, organic geochemistry and food
      chemistry. These advances have made it necessary to prepare intramolecular
      isotopic reference materials (RMs) to use for inter-laboratory calibration and/or
      inter-calibration among different analytical methods. METHODS: We evaluated the
      feasibility of preparing RMs using commercially available reagents for
      intramolecular carbon isotopic ratio measurement of acetic acid. The
      intramolecular carbon isotopic distribution of nine acetic acid and four sodium
      acetate reagents was determined with high precision using off-line pyrolysis
      combined with gas chromatography-combustion-isotope ratio mass spectrometry (GC-C
      IRMS). We also evaluated the potential alteration in the isotopic signature of
      acetic acid reagents by evaporation. RESULTS: The intramolecular carbon isotopic
      distributions for the acetic acid and sodium acetate reagents were determined
      with a precision of better than 0.450/00. We found that the isotopic values of
      these reagents spanned the carbon isotopic range of acetic acid in biological and
      environmental samples. We also found that the isotope fractionation associated
      with the evaporation of acetic acid occurs solely on the methyl position, the
      carboxyl position being unaffected. CONCLUSIONS: These commercially available
      reagents will be used as RMs in the future for inter-laboratory calibration
      and/or inter-calibration with another intramolecular isotopic measurement
      technique, namely quantitative (13) C NMR. In cases where acetic acid is being
      used as a RM, its storage must be carefully controlled to prevent evaporation.

PMID- 25559453
TI  - Detection and characterization of triamcinolone acetonide metabolites in human
      urine by liquid chromatography/tandem mass spectrometry after intramuscular
      administration.
AB  - RATIONALE: Glucocorticosteroids are prohibited in sports when used by systemic
      administrations (e.g. intramuscular, IM), whereas they are allowed using other
      ways of administration. Strategies to discriminate between administrations routes
      have to be developed by doping control laboratories. For this reason, the
      metabolism of triamcinolone acetonide (TA), one of the most used
      glucocorticosteroids, was studied using liquid chromatography coupled to tandem
      mass spectrometry (LC/MS/MS). METHODS: Urine samples obtained after IM
      administration of TA were analyzed using two sample treatments: (a) hydrolysis
      with beta-glucuronidase enzymes and liquid-liquid extraction under alkaline
      conditions, and (b) liquid-liquid extraction under acidic conditions. The
      extracts were analyzed by LC/MS/MS. RESULTS: TA, commercially available
      metabolites (6beta-hydroxytriamcinolone acetonide, 6beta-OH-TA, and
      triamcinolone), and their C20-reduced derivatives showed characteristic
      fragmentation behavior. Besides common product ions and neutral losses for
      corticosteroids containing fluorine, additional characteristic neutral losses (58
      Da, loss of acetone; 44 Da, loss of acetaldehyde) were observed in positive
      electrospray ionization. Based on that behavior, two complementary approaches
      were applied to detect TA metabolites: (a) open detection by precursor ion and
      neutral loss scan methods and (b) targeted detection by selected reaction
      monitoring methods (SRM) containing theoretical ion transitions of the potential
      metabolites. Two main compounds, TA and 6beta-OH-TA, and nine minor potential
      metabolites, were detected by open screening methods. Using SRM, two additional
      metabolites were detected. Some of the metabolites were characterized using
      reference standards and, for the rest of metabolites, feasible structures were
      proposed based on mass spectrometric data. CONCLUSIONS: Metabolites resulting
      from hydroxylation in C-6, oxidation of the 11-hydroxyl group, reduction of the
      Delta(4) double bond and oxidation of the side chain were detected. Some of them
      have not been previously described. Excretion profiles of the detected
      metabolites after IM administration are presented.

PMID- 25559455
TI  - Collision-induced cage folding of partially condensed polyhedral oligomeric
      silsesquioxanes (POSS) bearing naked and capped silanols.

PMID- 25559454
TI  - Stable isotope dilution liquid chromatography/mass spectrometry analysis of
      cellular and tissue medium- and long-chain acyl-coenzyme A thioesters.
AB  - RATIONALE: Acyl-Coenzyme A (CoA) thioesters are the principal form of activated
      carboxylates in cells and tissues. They are employed as acyl carriers that
      facilitate the transfer of acyl groups to lipids and proteins. Quantification of
      medium- and long-chain acyl-CoAs represents a significant bioanalytical challenge
      because of their instability. METHODS: Stable isotope dilution liquid
      chromatography/selected reaction monitoring-mass spectrometry (LC/SRM-MS)
      provides the most specific and sensitive method for the analysis of CoA species.
      However, relevant heavy isotope standards are not available and they are
      challenging to prepare by chemical synthesis. Stable isotope labeling by
      essential nutrients in cell culture (SILEC), developed originally for the
      preparation of stable isotope labeled short-chain acyl-CoA thioester standards,
      has now been extended to medium-chain and long-chain acyl-CoAs and used for
      LC/SRM-MS analyses. RESULTS: Customized SILEC standards with >98% isotopic purity
      were prepared using mouse Hepa 1c1c7 cells cultured in pantothenic-free media
      fortified with [(13) C3 (15) N1 ]-pantothenic acid and selected fatty acids. A
      SILEC standard in combination with LC/SRM-MS was employed to quantify cellular
      concentrations of arachidonoyl-CoA (a representative long-chain acyl-CoA) in two
      human colon cancer cell lines. A panel of SILEC standards was also employed in
      combination LC/SRM-MS to quantify medium- and long-chain acyl-CoAs in mouse
      liver. CONCLUSIONS: This new SILEC-based method in combination with LC/SRM-MS
      will make it possible to rigorously quantify medium- and long-chain acyl-CoAs in
      cells and tissues. The method will facilitate studies of medium- and long-chain
      acyl-CoA dehydrogenase deficiencies as well as studies on the role of medium- and
      long-chain acyl-CoAs in cellular metabolism.

PMID- 25559456
TI  - Persistence of pollination mutualisms in the presence of ants.
AB  - This paper considers plant-pollinator-ant systems in which the plant-pollinator
      interaction is mutualistic but ants have both positive and negative effects on
      plants. The ants also interfere with pollinators by preventing them from
      accessing plants. While a Beddington-DeAngelis (BD) formula can describe the
      plant-pollinator interaction, the formula is extended in this paper to
      characterize the pollination mutualism under the ant interference. Then, a plant
      pollinator-ant system with the extended BD functional response is discussed, and
      global dynamics of the model demonstrate the mechanisms by which pollination
      mutualism can persist in the presence of ants. When the ant interference is
      strong, it can result in extinction of pollinators. Moreover, if the ants depend
      on pollination mutualism for survival, the strong interference could drive
      pollinators into extinction, which consequently lead to extinction of the ants
      themselves. When the ant interference is weak, a cooperation between plant-ant
      and plant-pollinator mutualisms could occur, which promotes survival of both ants
      and pollinators, especially in the case that ants (respectively, pollinators)
      cannot survive in the absence of pollinators (respectively, ants). Even when the
      level of ant interference remains invariant, varying ants' negative effect on
      plants can result in survival/extinction of both ants and pollinators. Therefore,
      our results provide an explanation for the persistence of pollination mutualism
      when there exist ants. 

PMID- 25559457
TI  - Optimal harvesting for a predator-prey agent-based model using difference
      equations.
AB  - In this paper, a method known as Pareto optimization is applied in the solution
      of a multi-objective optimization problem. The system in question is an agent
      based model (ABM) wherein global dynamics emerge from local interactions. A
      system of discrete mathematical equations is formulated in order to capture the
      dynamics of the ABM; while the original model is built up analytically from the
      rules of the model, the paper shows how minor changes to the ABM rule set can
      have a substantial effect on model dynamics. To address this issue, we introduce
      parameters into the equation model that track such changes. The equation model is
      amenable to mathematical theory-we show how stability analysis can be performed
      and validated using ABM data. We then reduce the equation model to a simpler
      version and implement changes to allow controls from the ABM to be tested using
      the equations. Cohen's weighted kappa is proposed as a measure of similarity
      between the equation model and the ABM, particularly with respect to the
      optimization problem. The reduced equation model is used to solve a multi
      objective optimization problem via a technique known as Pareto optimization, a
      heuristic evolutionary algorithm. Results show that the equation model is a good
      fit for ABM data; Pareto optimization provides a suite of solutions to the multi
      objective optimization problem that can be implemented directly in the ABM.

PMID- 25559458
TI  - The effect of making a 'third dose assumption' on HPV coverage estimates.

PMID- 25559459
TI  - Graphene-Co3O4 nanocomposite as electrocatalyst with high performance for oxygen
      evolution reaction.
AB  - Graphene-Co3O4 composite with a unique sandwich-architecture was successfully
      synthesized and applied as an efficient electrocatalyst for oxygen evolution
      reaction. Field emission scanning electron microscopy (FESEM) and transmission
      electron microscopy (TEM) analyses confirmed that Co3O4 nanocrystals were
      homogeneously distributed on both sides of graphene nanosheets. The obtained
      composite shows enhanced catalytic activities in both alkaline and neutral
      electrolytes. The onset potential towards the oxygen evolution reaction is 0.406
      V (vs. Ag/AgCl) in 1 M KOH solution, and 0.858 V (vs. Ag/AgCl) in neutral
      phosphate buffer solution (PBS), respectively. The current density of 10 mA/cm(2)
      has been achieved at the overpotential of 313 mV in 1 M KOH and 498 mV in PBS.
      The graphene-Co3O4 composite also exhibited an excellent stability in both
      alkaline and neutral electrolytes. In particular, no obvious current density
      decay was observed after 10 hours testing in alkaline solution and the morphology
      of the material was well maintained, which could be ascribed to the synergistic
      effect of combining Co3O4 and graphene.

PMID- 25559460
TI  - Tranexamic acid--an old drug still going strong and making a revival.
AB  - Experience with tranexamic acid, an indirect fibrinolytic inhibitor, started as
      soon as it was released from Shosuke Okamoto's lab in the early 1960s. It was
      first prescribed to females with heavy menstrual blood loss and to patients with
      hereditary bleeding disorders. Soon the indications were widened to elective
      surgery because of its blood saving effects. Contraindications are few, most
      important is ongoing venous or arterial thrombosis and allergy to tranexamic
      acid, and the doses has to be reduced in renal insufficiency. In randomized
      controlled trials, however, patients with other risk factors are excluded as well
      (patients with history of cardiovascular disease, thromboembolism, bleeding
      diathesis, renal failure with creatinine >250MUmol/L, pregnancy, and patients on
      treatment with anticoagulants). Recent meta-analyses of several randomized
      controlled trials in orthopedic arthroplasty have shown that tranexamic acid
      reduces peri- and postoperative blood loss, blood transfusion requirements and
      reoperations caused by bleedings. In general, the preoperative dose was 10
      15mg/kg i.v. (or 1g), followed or not, by one or two doses, some as continuous
      infusion i.v. To validate relationship between dose and effect more data are
      needed. No evidence was found of increased thromboembolic accidents or other
      adverse events in the patients on tranexamic acid compared to the control groups.
      In major cardiac surgery tranexamic acid has been used in a large number of
      controlled trials with various dosing schemes in which the highest dosages seem
      to be associated with neurotoxicity; therefore a maximum total dose of 100mg/kg
      especially in patients over 50years of age is recommended by ISMICS
      (International Society for Minimally Invasive Cardiothoracic Surgery). Other
      indications for tranexamic acid are reviewed here as well. In recent years the
      extensive trial in severe trauma with massive bleedings using tranexamic acid was
      presented, CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant
      Haemorrhage) comprising more than 20,000 patients. It showed that the survival
      was increased when tranexamic acid was given early after the accident compared to
      placebo; further studies are taking place is this field to get more information.
      Of utmost importance is the ongoing WOMAN (World Maternal Antifibrinolytic) a
      randomized, double-blind, placebo controlled trial among 15,000 with clinical
      diagnosis of postpartum haemorrhage bearing in mind that each year a large number
      of women in low and middle income countries, die from causes related to
      childbirth. In summary, we consider tranexamic acid is a drug of great value to
      reduce almost any kind of bleeding, it is cheap and convenient to use and has
      principally few contraindications. It may be added, that tranexamic acid is
      included in the WHOs list of essential medicines. 

PMID- 25559461
TI  - The JAK2 V617F mutational status and allele burden may be related with the risk
      of venous thromboembolic events in patients with Philadelphia-negative
      myeloproliferative neoplasms.
AB  - INTRODUCTION: Patients with Philadelphia-negative myeloproliferative neoplasms
      (Ph(-) MPNs) are at increased risk of thromboembolic and hemorrhagic
      complications. The aim of the study was to determine the relationship between
      JAK2 V617F mutational status, JAK2 V617F allele burden and the risk of vascular
      complications occurrence. MATERIALS AND METHODS: Analysis was performed in a
      cohort of 186 patients diagnosed with polycythemia vera (53), essential
      thrombocythemia (114), primary myelofibrosis (11), and unclassified MPN (8). The
      risk of vascular complications development was analyzed in 126 JAK2 V617F
      positive patients with respect to allele burden assessed with allele-specific
      'real-time' quantitative polymerase chain reaction (AS RQ-PCR). RESULTS: Overall
      prevalence of any vascular complications was 44.6%. Arterial thrombosis occurred
      in 20.4%, venous thromboembolism (VTE) in 11.3%, bleeding episodes in 24.7% of
      patients. Individuals harboring JAK2 V617F mutation, regardless of MPN type, were
      at higher risk of VTE (OR=5.15, 95%CI: 1.16-22.90, P=0.024), mainly deep vein
      thrombosis (DVT). JAK2 allele burden higher than 20% identified patients with 7.4
      fold increased risk of VTE (95%CI: 1.6-33.7, P=0.004), but not of arterial
      thrombosis, neither of bleeding complications, and remained the only significant
      VTE risk factor in multivariate logistic regression. High allele burdens (over
      50%) were strikingly associated with proximal DVT cases, but not with distal DVT.
      CONCLUSIONS: The group of MPN patients with JAK2 V617F allele burden higher than
      20% may benefit the most from vigilant monitoring and appropriate prophylaxis
      against vascular events. Inclusion of JAK2 V617F mutant allele burden in new risk
      stratifications seems to be justified and requires controlled prospective trials.

PMID- 25559462
TI  - Biosynthesis, characterization, and hemostasis potential of tailor-made poly(3
      hydroxybutyrate-co-3-hydroxyvalerate) produced by Haloferax mediterranei.
AB  - We report the biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) random
      copolymers (R-PHBV) or higher-order copolymers (O-PHBV) in Haloferax
      mediterranei, with adjustable 3-hydroxyvalerate (3HV) incorporation by cofeeding
      valerate with glucose. Their microchemical structure, molecular weight and its
      distribution, and thermal and mechanical properties were characterized by NMR,
      GPC, DSC, TGA, and universal testing machine, respectively. (13)C NMR studies
      showed that O-PHBV copolymers consisted of short segments of PHB and PHV
      covalently linked together with random PHBV segments. Consistently, two Tg were
      observed in the DSC curves of O-PHBV. The "blocky" feature of O-PHBV enhanced
      crystallinity percentages and improved Young's modulus. Notably, the film of one
      O-PHBV copolymer, O-PHBV-1, showed unique foveolar cluster-like surface
      morphology with high hydrophobicity and roughness, as characterized using static
      contact angle and SEM and AFM analyses. It also exhibited increased platelet
      adhesion and accelerated blood clotting. The excellent hemostatic properties
      endow this copolymer with great potential in wound healing. 

PMID- 25559463
TI  - Endoglin (CD105) expression in sinonasal polyposis.
AB  - Despite appropriate surgical therapy, 5-10 % of patients with chronic
      rhinosinusitis (CRS) and nasal polyps (NP) experience disease recurrences. It has
      been suggested that angiogenesis may relate to the pathogenesis and prognosis of
      CRS with NP. Endoglin (CD105) is a component of the receptor complex of
      transforming growth factor-beta, a pleiotropic cytokine that modulates
      angiogenesis. A series of patients treated surgically for CRS with NP was
      analyzed to assess the relationship between CD105 expression, main
      clinicopathological features, and recurrence rate. The immunohistochemical
      expression of CD105 was assessed in 70 patients consecutively operated for CRS
      with NP. In the univariate setting, the presence of CD105 (1/0) showed a trend
      towards a significant association with increasing NP dimensions (p = 0.054).
      Intensity of CD105 reaction was also significantly associated with NP size (0.04)
      and with an eosinophilic histology (p = 0.048). In our multivariate setting, only
      asthma (p = 0.016), hypereosinophilia (p = 0.022), and preoperative polyposis
      score (p = 0.046) retained their independent prognostic significance in relation
      to NP recurrence. Further efforts are needed to elucidate the biological,
      angiogenic and proliferative mechanisms behind recurrent NP. Our preliminary
      results support the clinical utility of extra postoperative care, in terms of
      closer follow-ups and medication with oral anti-histamines, topical and/or oral
      steroids, and antileukotrienes in patients with asthma, advanced nasal polyposis
      at presentation, and serum hypereosinophilia.

PMID- 25559464
TI  - Expression and distribution of epithelial sodium channel in nasal polyp and nasal
      mucosa.
AB  - To evaluate the expression and location of epithelial sodium channels (ENaCs) in
      human nasal polyp and normal nasal mucosa, and to characterize the relevance of
      ENaCs to the development of NPs. Nasal polyp tissue from 17 patients and nasal
      mucosa from ten patients were obtained through endoscopic sinus surgery. The mRNA
      concentrations of ENaC-alpha, beta, and gamma were detected by real-time
      polymerase chain reaction. The expression of ENaC-alpha was detected using
      western blot and immunofluorescence techniques. The distribution of ENaC-alpha in
      mucosal tissue was observed using a laser scanning confocal microscope. The
      transcriptional expression of three subunits of ENaC was in the following order:
      alpha > beta > gamma, in both groups. The transcriptional expression of alpha,
      beta, and gamma subunits of ENaC was elevated in nasal polyp compared to nasal
      mucosa (p < 0.01). ENaC-alpha expression was higher in nasal polyp than in nasal
      mucosa (p < 0.05). Immunofluorescent staining indicated that ENaC-alpha protein
      was distributed in the epithelial cell apical membrane. The expression of ENaC is
      upregulated in human nasal polyp, which might in turn facilitate the formation
      and development of nasal polyp.

PMID- 25559465
TI  - Pharyngoesophageal perforation 3 years after anterior cervical spine surgery: a
      rare case report and literature review.
AB  - Pharyngoesophageal perforation after anterior cervical spine surgery is rare and
      the delayed cases were more rarely reported but potentially life-threatening. We
      report a case of pharyngoesophageal perforation 3 years after anterior cervical
      spine surgery. The patient presented with dysphagia, fever, left cervical mass
      and developing dyspnea 3 years after cervical spine surgery for trauma. After
      careful examinations, he underwent an emergency tracheostomy, neck exploration,
      hardware removal, abscess drainage and infected tissue debridement. 14 days after
      surgery, CT of the neck with oral contrast demonstrated no contrast extravasation
      from the esophagus. Upon review of literature, only 14 cases of
      pharyngoesophageal perforation more than 1 year after anterior cervical spine
      surgery were found. We discussed possible etiology, diagnosis and management and
      concluded that in cases of dysphagia, dyspnea, cervical pain, swelling and edema
      of the cervical area even long time after anterior cervical spine surgery,
      potential pharyngoesophageal damage should be considered.

PMID- 25559466
TI  - Comparative analysis of preoperative diagnostic values of HRCT and CBCT in
      patients with histologically diagnosed otosclerotic stapes footplates.
AB  - This prospective case review was performed with the aim to compare and asses the
      diagnostic values of cone-beam computed tomography (CBCT) and high-resolution
      computed tomography (HRCT) in the preoperative evaluation of otosclerosis. A
      total of 43 patients with histologically confirmed stapedial otosclerosis, who
      underwent unilateral stapedectomies were analyzed. Preoperative temporal bone
      CBCT and HRCT scans were performed in all cases. Both CBCT and HRCT imaging were
      characterized by a slice thickness of 0.4-0.625 mm and multiplanar image
      reconstruction. Histopathologic examination of the removed stapes footplates was
      performed in all cases. Findings of CBCT and HRCT were categorized according to
      the modified Marshall's grading system (fenestral or retrofenestral lesions).
      Histopathologic results were correlated with multiplanar reconstructed CBCT and
      HRCT scans, respectively. Negative control groups for CBCT (n = 36) and HRCT (n =
      27) examinations consisted of patients, who underwent CBCT imaging due to various
      dental disorders or HRCT analysis due to idiopathic sudden sensorineural hearing
      loss. Histologically active foci of otosclerosis (n = 31, 72 %) were identified
      by both CBCT and HRCT in all cases with a sensitivity of 100 %. However, CBCT
      could not detect histologically inactive otosclerosis (n = 12, 23 %; sensitivity
      0 %). In contrast, HRCT showed inactive otosclerosis with a sensitivity of 59.3
      %. According to CBCT results, no retrofenestral lesions were found and the
      overall sensitivity for hypodense lesions was 61.37 %. In conclusion, CBCT is a
      robust imaging method in the detection of histologically active fenestral
      hypodense foci of otosclerosis with high sensitivity and radiologic specificity.
      In the light of these results, HRCT still remains the basic imaging method in the
      preoperative diagnosis of otosclerosis, since it has much greater sensitivity and
      specificity in the detection of retrofenestral hypodense lesions and
      histologically inactive otosclerotic foci in the oval window niche.

PMID- 25559467
TI  - Silica nanoparticles as substrates for chelator-free labeling of oxophilic
      radioisotopes.
AB  - Chelator-free nanoparticles for intrinsic radiolabeling are highly desirable for
      whole-body imaging and therapeutic applications. Several reports have
      successfully demonstrated the principle of intrinsic radiolabeling. However, the
      work done to date has suffered from much of the same specificity issues as
      conventional molecular chelators, insofar as there is no singular nanoparticle
      substrate that has proven effective in binding a wide library of radiosotopes.
      Here we present amorphous silica nanoparticles as general substrates for chelator
      free radiolabeling and demonstrate their ability to bind six medically relevant
      isotopes of various oxidation states with high radiochemical yield. We provide
      strong evidence that the stability of the binding correlates with the hardness of
      the radioisotope, corroborating the proposed operating principle. Intrinsically
      labeled silica nanoparticles prepared by this approach demonstrate excellent in
      vivo stability and efficacy in lymph node imaging. 

PMID- 25559468
TI  - Deoxycholic acid-modified polyethylenimine based nanocarriers for RAGE siRNA
      therapy in acute myocardial infarction.
AB  - The activation of receptor for advanced glycation end products (RAGE) signaling
      is mainly associated with myocardial ischemia/reperfusion injury. Thus the
      blockade of RAGE-ligands axis can be considered as a potential therapeutic
      strategy to protect myocardial infarction after ischemia/reperfusion injury.
      Herein, we strengthened the cardioprotective effect with combinatorial treatment
      of soluble RAGE (sRAGE) and RAGE siRNA (siRAGE) causing more effective
      suppression of RAGE-mediated signaling transduction. For pharmacological blockade
      of RAGE, sRAGE, the extracellular ligand binding domain of RAGE, acts as a
      pharmacological ligand decoy and inhibits the interaction between RAGE and its
      ligands. For genetic deletion of RAGE, siRAGE suppresses the expression of RAGE
      by participating in RNA interference mechanism. Therefore, we combined these two
      RAGE blockade/deletion strategies and investigated the therapeutic effects on rat
      ischemic and reperfused myocardium. According to our results, based on RAGE
      expression level analysis and infarct size/fibrosis measurement, co-treatment of
      sRAGE and siRAGE exhibited synergic cardioprotective effects; thus the newly
      designed regimen can be considered as a promising candidate for the treatment of
      myocardial infarction. 

PMID- 25559469
TI  - How narrow a network is too narrow?

PMID- 25559470
TI  - Insulin resistance is associated with intraocular pressure elevation in a non
      obese Korean population.
AB  - Based on reports of an association between elevated intraocular pressure (IOP)
      and metabolic syndrome (MetS), and the major role of insulin resistance (IR) in
      MetS pathogenesis, a positive association between IOP and IR has been
      hypothesized. Although Asian populations tend to have lower body mass indices
      (BMIs) than Western populations, they tend to have a higher risk of developing
      MetS. This study examined the hypothesis that the association between IOP and IR
      differs by obesity status in an Asian population, by examining a nationally
      representative sample of South Korean adults. Data collected from 4,621 South
      Korean adults regarding demographic, lifestyle, and laboratory parameters by the
      2010 Korea National Health and Nutrition Examination Survey were subjected to
      linear regression analysis to evaluate the relationship between IOP and metabolic
      profiles. After adjusting for confounding factors, the data were subjected to
      multiple linear regression analysis to examine the association between IR, as
      measured by the homeostasis model assessment of insulin resistance (HOMA-IR), and
      IOP. Obesity was defined as BMI>=27.5 kg/m2, and the subjects were divided into
      obese vs. non-obese groups for investigation of the association between IR and
      IOP according to obesity status. IOP was found to correlate with fasting blood
      sugar, total cholesterol, insulin, and HOMA-IR values in non-obese men; and with
      BMI, waist circumference, triglycerides, total cholesterol, HOMA-IR, and low
      density lipoprotein cholesterol values in non-obese women, whereas no association
      between IOP and IR was found in obese men or women. IOP was significantly
      associated with IR in non-obese men and women after adjusting for age, and in non
      obese men after adjusting for age, BMI, and lifestyle and demographic factors.
      These findings indicate that a positive and independent relationship exists
      between IOP and IR in non-obese individuals only, suggesting that other factors
      likely contribute to IOP elevation in obese individuals. 

PMID- 25559471
TI  - Advances in understanding the pathogenesis of systemic anaplastic large cell
      lymphomas.
AB  - The currently used 2008 World Health Organization classification recognizes two
      types of systemic anaplastic large T cell lymphoma according to ALK protein
      expression in tumour cells. First, the 'anaplastic large cell lymphoma, ALK
      positive' (ALK(+) ALCL) that is characterized by the presence of ALK gene
      rearrangements and consequent ALK protein expression, and, second, the
      'anaplastic large cell lymphoma, ALK negative' (ALK(-) ALCL) that is a
      provisional entity lacking ALK protein expression but cannot be distinguished
      morphologically from ALK(+) ALCL. In this review we summarize the current
      knowledge on the genetic lesions and biological features that underlie the
      pathogenesis of ALK(+) and the ALK(-) ALCL and that can lead to the use of
      targeted anti-cancer agents. 

PMID- 25559472
TI  - 5-HT3 receptor antagonists do not alter spontaneous contraction of pregnant
      myometrium in vitro.
AB  - BACKGROUND: 5-HT3 receptor antagonists are effective antiemetics for
      perioperative use. However, their effects on myometrial contractility remain
      unknown. We examined whether three different 5-HT3 receptor antagonists could
      affect the contraction of human myometrium. METHODS: Samples of human myometrium
      were taken from parturients undergoing elective cesarean delivery. Effects of
      ondansetron, granisetron and tropisetron (over a range of 1-10(4)ng/mL) on
      spontaneous contraction (ratios of amplitude, interval, and duration of the
      contraction) were examined and compared to saline controls (n=6 for each agent).
      RESULTS: None of the three 5-HT3 receptor antagonists significantly affected
      myometrial contraction. CONCLUSION: 5-HT3 receptor antagonists do not affect the
      contraction of myometrial strips isolated from term pregnant women.

PMID- 25559473
TI  - Recommendations for cardiac chamber quantification by echocardiography in adults:
      an update from the American Society of Echocardiography and the European
      Association of Cardiovascular Imaging.
AB  - The rapid technological developments of the past decade and the changes in
      echocardiographic practice brought about by these developments have resulted in
      the need for updated recommendations to the previously published guidelines for
      cardiac chamber quantification, which was the goal of the joint writing group
      assembled by the American Society of Echocardiography and the European
      Association of Cardiovascular Imaging. This document provides updated normal
      values for all four cardiac chambers, including three-dimensional
      echocardiography and myocardial deformation, when possible, on the basis of
      considerably larger numbers of normal subjects, compiled from multiple databases.
      In addition, this document attempts to eliminate several minor discrepancies that
      existed between previously published guidelines. 

PMID- 25559474
TI  - Guidelines for the use of echocardiography as a monitor for therapeutic
      intervention in adults: a report from the American Society of Echocardiography.

PMID- 25559475
TI  - Walking the walk...or achieving quality is harder than it seems.

PMID- 25559476
TI  - Abnormal contractile reserve to exercise: a stress echocardiographic abnormality
      that may be associated with myocardial rather than coronary artery disease.

PMID- 25559477
TI  - It's an international affair.

PMID- 25559478
TI  - New hire training.

PMID- 25559479
TI  - Choosing wisely in perioperative echocardiography.

PMID- 25559480
TI  - Shoulder-Muscle Activation in Individuals With Previous Shoulder Injuries.
AB  - CONTEXT: Understanding how muscles activate in a population with a previous
      glenohumeral-joint (GH) injury may help clinicians understand how to build a
      conservative treatment plan to strengthen or activate the specific muscles in an
      attempt to reduce recurrent shoulder injury and development of GH laxity.
      OBJECTIVE: To investigate muscle-activation differences between the previously
      injured limb of individuals with a history of GH-joint injury and healthy matched
      controls during functional isometric contractions. DESIGN: Case control. SETTING:
      University research laboratory. PARTICIPANTS: 17 individuals (8 women, 9 men; age
      22.3 +/- 2.6 y, height 172.4 +/- 8.8 cm, mass 75.4 +/- 16.5 kg) with previous
      unilateral shoulder pain and 17 (8 women, 9 men; age 22.9 +/- 3.9 y, height 170.9
      +/- 11.3 cm, mass 73.6 +/- 22.9 kg) with no history of shoulder pain or injury.
      INTERVENTION(S): Diagnostic ultrasound measurements of the supraspinatus were
      completed in both resting and contracted states to assess changes in muscle
      thickness. Manual muscle tests (anterior deltoid, upper trapezius, infraspinatus,
      lower trapezius, serratus anterior) and functional isometric contractions
      (forward flexion, scaption, abduction) were measured using electromyography. MAIN
      OUTCOME MEASURES: Peak, normalized activation of each muscle and supraspinatus
      thickness activation ratio were compared between groups and bilaterally within
      groups using separate ANOVAs. RESULTS: The anterior deltoid was significantly
      less activated during all functional isometric tasks in previously injured
      subjects than in healthy subjects (P = .024). In previously injured subjects, the
      involved limb-lower trapezius was significantly less activated during scaption
      and abduction tasks than the contralateral side (P = .022 and P = .031,
      respectively). CONCLUSIONS: There were decreases in muscle activation in the
      anterior deltoid between previously injured and healthy people, as well as in the
      lower trapezius, in previously injured subjects. Understanding the source of
      muscle-activation deficits can help clinicians focus rehabilitation exercises on
      specific muscles.

PMID- 25559481
TI  - How does response inhibition influence decision making when gambling?
AB  - Recent research suggests that response inhibition training can alter impulsive
      and compulsive behavior. When stop signals are introduced in a gambling task,
      people not only become more cautious when executing their choice responses, they
      also prefer lower bets when gambling. Here, we examined how stopping motor
      responses influences gambling. Experiment 1 showed that the reduced betting in
      stop-signal blocks was not caused by changes in information sampling styles or
      changes in arousal. In Experiments 2a and 2b, people preferred lower bets when
      they occasionally had to stop their response in a secondary decision-making task
      but not when they were instructed to respond as accurately as possible.
      Experiment 3 showed that merely introducing trials on which subjects could not
      gamble did not influence gambling preferences. Experiment 4 demonstrated that the
      effect of stopping on gambling generalized to different populations. Further, 2
      combined analyses suggested that the effect of stopping on gambling preferences
      was reliable but small. Finally, Experiment 5 showed that the effect of stopping
      on gambling generalized to a different task. On the basis of our findings and
      earlier research, we propose that the presence of stop signals influences
      gambling by reducing approach behavior and altering the motivational value of the
      gambling outcome.

PMID- 25559482
TI  - Bioassay-based isolation and identification of phenolics from sweet cherry that
      promote active glucose consumption by HepG2 cells.
AB  - A variety of phenolics had been found to be functional in promoting cellular
      glucose consumption that is important for blood glucose regulation. Sweet cherry
      (Prunus avium) is rich in such kinds of phenolics, including hydrocinnamic acids,
      anthocyanins, flavonols, and flavan-3-ols. Furthermore, a sweet cherry phenolics
      rich extract (PRE) was found to be effective in promoting HepG2 glucose
      consumption. Seventeen components were preliminarily identified by HPLC-ESI-MS,
      including 9 hydrocinnamic acids, 4 anthocyanins, 3 flavonols, and 1 flavan-3-ol.
      To investigate the cellular glucose consumption-promotion activity of different
      phneolics subclasses, the phenolics were further fractionated into an anthocyanin
      rich fraction (ARF), hydrocinnamic acid-rich fraction (HRF), and flavonol-rich
      fraction (FRF) through liquid-liquid extraction and mix-mode cation-exchange
      solid-phase extraction. The 3 fractions promoted HepG2 glucose consumption to
      different levels, with the promotion effects of HRF and FRF stronger than that of
      the ARF. The results provide guidance on the use of sweet cherry as a functional
      fruit. 

PMID- 25559483
TI  - [Global response to the ebola's threat].

PMID- 25559484
TI  - [Dyslipidaemia and vascular risk. A new evidence based review].
AB  - Dyslipidaemia is one of the major risk factors for ischaemic heart disease, the
      leading cause of death worldwide. Early detection and therapeutic intervention
      are key elements in the adequate prevention of cardiovascular disease. It is
      essential to have knowledge of the therapeutic arsenal available for their
      appropriate use in each of the clinical situations that might be presented in our
      patients. In the past 3 years, there has been a proliferation of multiple
      guidelines for the clinical management of patients with dyslipidaemia, with
      apparent contradictory messages regarding the achievement of the control
      objectives, which are confusing clinicians. This review aims to provide an
      updated overview of the situation as regards dyslipidaemia, based on the
      positioning of both European and American guidelines, through different risk
      situations and ending with the concept of atherogenic dyslipidaemia as a
      recognized cardiovascular risk factor. 

PMID- 25559485
TI  - Correction to: Liposome-mediated transfection with extract from neonatal rat
      cardiomyocytes induces transdifferentiation of human adipose-derived stem cells
      into cardiomyocytes.

PMID- 25559487
TI  - Heterogeneous electro-Fenton using modified iron-carbon as catalyst for 2,4
      dichlorophenol degradation: influence factors, mechanism and degradation pathway.
AB  - Modified iron-carbon with polytetrafluoroethylene (PTFE) was firstly investigated
      as heterogeneous electro-Fenton (EF) catalyst for 2,4-dichlorophenol (2,4-DCP)
      degradation in near neutral pH condition. The catalyst was characterized by
      scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and X
      ray diffraction (XRD), and the effects of some important operating parameters
      such as current intensity and pH on the 2,4-DCP degradation were investigated.
      After the catalyst modification with 20% PTFE, the degradation performance
      maintained well with much lower iron leaching, and at current intensity 100 mA,
      initial pH 6.7, catalyst loading 6 g/L, the degradation efficiency of 2,4-DCP
      could exceed 95% within 120 min treatment. Two-stage pseudo first-order kinetics
      of 2,4-DCP degradation was observed, including a slow anodic oxidation stage
      (first-stage) and much faster heterogeneous EF oxidation (second-stage), in which
      the automatic drop of pH in the first-stage initiated the Fe(2+) release from
      micro-electrolysis and thus benefited to the subsequent EF reaction. Aromatic
      intermediates such as 3,5-dichlorocatechol, 4,6-dichlororesorcinol and 2
      chlorohydroquinone were detected by GC-MS. Oxalic acid, acetic acid, formic acid
      and Cl(-) were quantified by ion chromatograph. Based on these analysis as well
      as the detection of H2O2 and OH, a possible mechanism and degradation pathway for
      2,4-DCP were proposed. This work demonstrated that such a heterogeneous EF using
      cheap modified Fe-C catalyst was promising for organic wastewater treatment in
      initial neutral pH condition.

PMID- 25559486
TI  - ACG clinical guideline: epidemiology, risk factors, patterns of presentation,
      diagnosis, and management of colon ischemia (CI).

PMID- 25559488
TI  - Combined metabolome and proteome analysis of the mantle tissue from Pacific
      oyster Crassostrea gigas exposed to elevated pCO2.
AB  - Ocean acidification (OA) has been found to affect an array of normal
      physiological processes in mollusks, especially posing a significant threat to
      the fabrication process of mollusk shell. In the current study, the impact of
      exposure to elevated pCO2 condition was investigated in mantle tissue of
      Crassostrea gigas by an integrated metabolomic and proteomic approach. Analysis
      of metabolome and proteome revealed that elevated pCO2 could affect energy
      metabolism in oyster C. gigas, marked by differentially altered ATP, succinate,
      MDH, PEPCK and ALDH levels. Moreover, the up-regulated calponin-2, tropomyosins
      and myosin light chains indicated that elevated pCO2 probably caused disturbances
      in cytoskeleton structure in mantle tissue of oyster C. gigas. This work
      demonstrated that a combination of proteomics and metabolomics could provide
      important insights into the effects of OA at molecular levels. 

PMID- 25559489
TI  - CdTe quantum dots conjugated to concanavalin A as potential fluorescent molecular
      probes for saccharides detection in Candida albicans.
AB  - Semiconductor colloidal quantum dots (QDs) have been applied in biological
      analysis due to their unique optical properties and their versatility to be
      conjugated to biomolecules, such as lectins and antibodies, acquiring specificity
      to label a variety of targets. Concanavalin A (Con A) lectin binds specifically
      to alpha-d-mannose and alpha-d-glucose regions of saccharides that are usually
      expressed on membranes of mammalian cells and on cell walls of microbials.
      Candida albicans is the most common fungal opportunistic pathogen present in
      humans. Therefore, in this work, this fungus was chosen as a model for
      understanding cells and biofilm-forming organisms. Here, we report an efficient
      bioconjugation process to bind CdTe (Cadmium Telluride) QDs to Con A, and applied
      the bioconjugates to label saccharide structures on the cellular surface of C.
      albicans suspensions and biofilms. By accomplishing hemagglutination experiments
      and circular dichroism, we observed that the Con A structure and biochemical
      properties were preserved after the bioconjugation. Fluorescence microscopy
      images of yeasts and hyphae cells, as well as biofilms, incubated with QDs-(Con
      A) showed a bright orange fluorescence profile, indicating that the cell walls
      were specifically labeled. Furthermore, flow cytometry measurements confirmed
      that over 93% of the yeast cells were successfully labeled by QD-(Con A) complex.
      In contrast, non-conjugated QDs or QDs-(inhibited Con A) do not label any kind of
      biological system tested, indicating that the bioconjugation was specific and
      efficient. The staining pattern of the cells and biofilms demonstrate that QDs
      were effectively bioconjugated to Con A with specific labeling of saccharide-rich
      structures on C. albicans. Consequently, this work opens new possibilities to
      monitor glucose and mannose molecules through fluorescence techniques, which can
      help to optimize phototherapy protocols for this kind of fungus. 

PMID- 25559490
TI  - The 17-propionate esterifying variants of bacteriochlorophyll-a and
      bacteriopheophytin-a in purple photosynthetic bacteria.
AB  - Most purple photosynthetic bacteria contain bacteriochlorophyll(BChl)-a (a
      magnesium complex) and bacteriopheophytin(BPhe)-a (its free base) as their
      photoactive pigments. These pigments are composed of two parts: a cyclic
      tetrapyrrole as the chromophore and a long hydrocarbon-chain as the propionate
      type esterifying group at the 17-position. The hydrocarbon-chain is usually an
      isoprenoid-type C20 phytyl (Phy) group in both the pigments. In the ester group
      of BChl-a, several variants such as geranylgeranyl (GG), dihydrogeranylgeranyl
      (DHGG) and tetrahydrogeranylgeranyl (THGG) groups were found in the final stage
      of BChl-a biosynthesis. On the other hand, the esterifying variants in BPhe-a
      have not been studied as much due to the lower levels of this pigment relative to
      BChl-a. The esterifying group does not affect the electronic absorption
      properties of such pigments in the monomeric state, but drastically alters the
      hydrophobicity. In this study, BChl-a and BPhe-a in the six phylogenetically
      distinct classes of purple bacteria were analyzed in terms of their esterifying
      groups in the 17-propionate residues, using high-performance liquid
      chromatography. Both BChls-a and BPhes-a carrying GG, DHGG and THGG in addition
      to the usual Phy were found for all the bacterial species studied at measurable
      levels. In some of the species, the ratio of BPhes-a esterified with GG, DHGG and
      THGG over the total BPhe-a drastically decreased in comparison with that of the
      corresponding BChls-a. Especially, the relative content of BPhe-a with GG largely
      decreased. This observation might indicate that BPhe-a as a cofactor of reaction
      centers was preferentially esterified with partially reduced and flexible chains
      (THGG and Phy) rather than less reduced and rigid ones (GG and DHGG). 

PMID- 25559491
TI  - CD4+ T cells apoptosis in Plasmodium vivax infection is mediated by activation of
      both intrinsic and extrinsic pathways.
AB  - BACKGROUND: Reduction in the number of circulating blood lymphocytes
      (lymphocytopaenia) has been reported during clinical episodes of malaria and is
      normalized after treatment with anti-malaria drugs. While this phenomenon is well
      established in malaria infection, the underlying mechanisms are still not fully
      elucidated. In the present study, the occurrence of apoptosis and its pathways in
      CD4+ T cells was investigated in naturally Plasmodium vivax-infected individuals
      from a Brazilian endemic area (Porto Velho - RO). METHODS: Blood samples were
      collected from P. vivax-infected individuals and healthy donors. The apoptosis
      was characterized by cell staining with Annexin V/FITC and propidium iodide and
      the apoptosis-associated gene expression profile was carried out using RT2
      Profiler PCR Array-Human Apoptosis. The plasma TNF level was determined by ELISA.
      The unpaired t-test or Mann-Whitney test was applied according to the data
      distribution. RESULTS: Plasmodium vivax-infected individuals present low number
      of leukocytes and lymphocytes with a higher percentage of CD4+ T cells in early
      and/or late apoptosis. Increased gene expression was observed for TNFRSF1B and
      Bid, associated with a reduction of Bcl-2, in individuals with P. vivax malaria.
      Furthermore, these individuals showed increased plasma levels of TNF compared to
      malaria-naive donors. CONCLUSIONS: The results of the present study suggest that
      P. vivax infection induces apoptosis of CD4+ T cells mediated by two types of
      signaling: by activation of the TNFR1 death receptor (extrinsic pathway), which
      is amplified by Bid, and by decreased expression of the anti-apoptotic protein
      Bcl-2 (intrinsic pathway). The T lymphocytes apoptosis could reflect a strategy
      of immune evasion triggered by the parasite, enabling their persistence but also
      limiting the occurrence of immunopathology.

PMID- 25559492
TI  - An amplified electrochemiluminescent aptasensor using Au nanoparticles capped by
      3,4,9,10-perylene tetracarboxylic acid-thiosemicarbazide functionalized C60
      nanocomposites as a signal enhancement tag.
AB  - A novel electrochemiluminescent (ECL) signal tag of Au nanoparticles capped by
      3,4,9,10-perylene tetracarboxylic acid-thiosemicarbazide functionalized C60
      nanocomposites (AuNPs/TSC-PTC/C60NPs) was developed for thrombin (TB) aptasensor
      construction based on the peroxydisulfate/oxygen (S2O8(2-)/O2) system. For signal
      tag fabrication, the C60 nanoparticles (C60NPs) were prepared and then coated
      with 3,4,9,10-perylene tetracarboxylic acid (PTCA) by pi-pi stacking
      interactions. Afterwards, thiosemicarbazide (TSC) was linked with PTCA
      functionalized C60NPs via amidation for further assembling Au nanoparticles
      (AuNPs). Finally, detection aptamer of thrombin (TBA 2) was labeled on the ECL
      signal amplification tag of AuNPs/TSC-PTC/C60NPs. Herein, TSC, with the active
      groups of -NH2 and -SH, was selected and introduced into the ECL S2O8(2-)/O2
      system for the first time, which could not only offer the active groups of -SH to
      absorb AuNPs for TBA 2 anchoring but also remarkably enhance the ECL signal of
      the S2O8(2-)/O2 system by the formation of TSC-PTC/C60NPs for signal
      amplification. Meanwhile, the sensing interface of a glassy carbon electrode
      (GCE) was modified by AuNPs/graphene (AuNPs/GR) nanocomposites with the large
      specific surface area and the active sites, followed by immobilization of thiol
      terminated thrombin capture aptamer (TBA 1). With the formation of the sandwich
      type structure of TBA 1, TB, and TBA 2 signal probes, a desirable enhanced ECL
      signal was measured in the testing buffer of an S2O8(2-)/O2 solution for
      detecting TB. The aptasensor exhibited a good linear relationship for TB
      detection in the range of 1 * 10(-5)-10 nM with a detection limit of 3.3 fM.

PMID- 25559493
TI  - Use of the Robson classification has improved understanding of caesarean section
      rates in France.

PMID- 25559494
TI  - The effect of acute alcohol intoxication on gut wall integrity in healthy male
      volunteers; a randomized controlled trial.
AB  - The aim of the study is to determine the effect of acute alcohol consumption on
      enterocytes. Chronic alcohol consumption has been known to induce a decrease in
      gut wall integrity in actively drinking alcoholics and patients with alcohol
      induced liver disease. Data on the extent of the damage induced by acute alcohol
      consumption in healthy human beings is scarce. Studies show that heavy incidental
      alcohol consumption is a growing problem in modern society. Data on this matter
      may provide insights into the consequences of this behavior for healthy
      individuals. In a randomized clinical trial in crossover design, 15 healthy
      volunteers consumed water one day and alcohol the other. One blood sample was
      collected pre-consumption, five every hour post-consumption, and one after 24 h.
      Intestinal fatty acid binding protein (I-FABP) was used as a marker for
      enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl
      transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide
      binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of
      translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory
      response to endotoxemia. Alcohol consumption caused a significant increase in
      serum I- and L-FABP levels, compared to water consumption. Levels increased
      directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14,
      and IL-6 levels were not significantly higher in the alcohol group. Moderate
      acute alcohol consumption immediately damages the enterocyte but does not seem to
      cause endotoxemia.

PMID- 25559495
TI  - Should we educate care staff to improve the oral health and oral hygiene of
      people with intellectual disability in residential care? Real world lessons from
      a randomized controlled trial.
AB  - This study assessed the impact of a multitiered oral health educational program
      on the oral health and oral hygiene of people with intellectual disabilities
      (ID). In a controlled pretest, posttest trial, with cluster randomization, a
      pyramidal training program was delivered to residential staff who cared for a
      randomly allocated, purposively stratified intervention group of people with ID
      living in community care homes. A control group lived in centers where staff
      received no training. Clinical measures were carried out pre- and posttest.
      Difference in Modified Gingival Index (MGI) and Plaque Index (PI) was measured
      posttest using ANCOVA. Seventy-six participants took part, representing 49.0% of
      the invited sample (n = 155). Fourteen did not receive clinical examination.
      There was one dropout 6-9 months later. A 10.5% and 8.5% reduction in mean MGI
      and PI was evident at posttest but did not show statistically significant
      difference, when controlling for baseline covariates (p > 0.05, ANCOVA). Mean MGI
      and PI scores were not significantly different among people with ID whose care
      staff had and had not received oral health training. Limitations are discussed.
      The results indicate that this program failed to significantly improve oral
      health or oral hygiene, despite the intervention being "educationally"
      successful. More research is needed. 

PMID- 25559496
TI  - Comparative analysis of tropaeolin adsorption onto raw and acid-treated
      kaolinite: optimization by Response Surface Methodology.
AB  - The comparative adsorption of Tropaeolin (TP) onto raw kaolinite (RK) and
      kaolinite submitted to acid treatment (AK) was studied. RK and AK were
      characterized by zeta potential and energy dispersive X-ray spectroscopy (EDS).
      The adsorption was investigated using Composite Central Design (CCD) and the
      parameters evaluated were initial TP solution concentration, quantity of
      adsorbent and the pH of the solution. The optimized parameters were: initial TP
      solution concentration of 75 mg L(-1), pH 4 and 0.12 g adsorbent. Kinetic data
      were evaluated by pseudo-first order, pseudo-second order and Avrami models. The
      equilibrium adsorption was analyzed by Langmuir, Freundlich and Sips isotherms.
      The kinetic data were best fitted to the pseudo-second order model. The Sips
      isotherm model gives the better correlation to predict the adsorption
      equilibrium. The maximum adsorption capacities were 18.3 mg g(-1) and 23.2 mg g(
      1) for RK and AK, respectively. The calculated thermodynamic parameters showed
      that the process was spontaneous, endothermic and involving the disorganization
      of the adsorption system for both adsorbents. The desorption step showed that the
      AK sample was more suitable as an adsorbent.

PMID- 25559497
TI  - Selecting enhancing solutions for electrokinetic remediation of dredged sediments
      polluted with fuel.
AB  - In this paper a procedure for selecting the enhancing solutions in electrokinetic
      remediation experiments is proposed. For this purpose, dredged marine sediment
      was contaminated with fuel, and a total of 22 different experimental conditions
      were tested, analysing the influence of different enhancing solutions by using
      three commercial non-ionic surfactants, one bio-surfactant, one chelating agent,
      and one weak acid. Characterisation, microelectrophoretic and electrokinetic
      remediation trials were carried out. The results are explained on the basis of
      the interactions between the fuel, the enhancing electrolytes and the matrix. For
      one specific system, the electrophoretic zeta potential, (zeta), of the
      contaminated matrix in the solution was found to be related to the electroosmotic
      averaged zeta in the experiment and not to the efficiency in the extraction. This
      later was correlated to a parameter accounting for both contributions, the
      contaminant and the enhancing solution, calculated on the basis of differences in
      the electrophoretic zeta in different conditions which has allowed to propose a
      methodology for selection of enhancing solutions. 

PMID- 25559498
TI  - Recombinant interleukin-1 receptor antagonist attenuates the severity of chronic
      pancreatitis induced by TNBS in rats.
AB  - Chronic pancreatitis (CP) is a common disease in the department of
      gastroenterology, with the main symptoms of exocrine and/or endocrine
      insufficiency and abdominal pain. The pathogenic mechanism of CP is still not
      fully clarified and the aims of treatment now are to relieve symptoms. In this
      study, we attempted to find a connection between interleukin-1beta (IL-1beta) and
      interleukin-1 receptor antagonist (IL-1Ra) in trinitrobenzene sulfonic acid
      (TNBS)-induced chronic pancreatitis, and then the therapeutic effect of
      recombinant IL-1Ra was also detected in the CP model. Chronic pancreatitis was
      induced by intraductal infusion of TNBS in SD rats followed by a consecutive
      administration of rIL-1Ra, and the histological changes and collagen content in
      the pancreas were measured, as well as the abdominal hypersensitivity. We found
      that rhIL-1Ra could attenuate the severity of chronic pancreatic injury, modulate
      the extracellular matrix secretion, focal proliferation and apoptosis, and
      cellular immunity in TNBS-induced CP. Interestingly, rIL-1Ra could also block the
      pancreatitis-induced referred abdominal hypersensitivity. In conclusion, IL-1Ra
      may play a protective role in CP and rIL-1Ra would be a potential therapeutic
      target for the treatment of CP, while its possible mechanisms and clinical usage
      still need further investigation. 

PMID- 25559499
TI  - Identifying cooperative transcription factors in yeast using multiple data
      sources.
AB  - BACKGROUND: Transcriptional regulation of gene expression is usually accomplished
      by multiple interactive transcription factors (TFs). Therefore, it is crucial to
      understand the precise cooperative interactions among TFs. Various kinds of
      experimental data including ChIP-chip, TF binding site (TFBS), gene expression,
      TF knockout and protein-protein interaction data have been used to identify
      cooperative TF pairs in existing methods. The nucleosome occupancy data is not
      yet used for this research topic despite that several researches have revealed
      the association between nucleosomes and TFBSs. RESULTS: In this study, we
      developed a novel method to infer the cooperativity between two TFs by
      integrating the TF-gene documented regulation, TFBS and nucleosome occupancy
      data. TF-gene documented regulation and TFBS data were used to determine the
      target genes of a TF, and the genome-wide nucleosome occupancy data was used to
      assess the nucleosome occupancy on TFBSs. Our method identifies cooperative TF
      pairs based on two biologically plausible assumptions. If two TFs cooperate, then
      (i) they should have a significantly higher number of common target genes than
      random expectation and (ii) their binding sites (in the promoters of their common
      target genes) should tend to be co-depleted of nucleosomes in order to make these
      binding sites simultaneously accessible to TF binding. Each TF pair is given a
      cooperativity score by our method. The higher the score is, the more likely a TF
      pair has cooperativity. Finally, a list of 27 cooperative TF pairs has been
      predicted by our method. Among these 27 TF pairs, 19 pairs are also predicted by
      existing methods. The other 8 pairs are novel cooperative TF pairs predicted by
      our method. The biological relevance of these 8 novel cooperative TF pairs is
      justified by the existence of protein-protein interactions and co-annotation in
      the same MIPS functional categories. Moreover, we adopted three performance
      indices to compare our predictions with 11 existing methods' predictions. We show
      that our method performs better than these 11 existing methods in identifying
      cooperative TF pairs in yeast. Finally, the cooperative TF network constructed
      from the 27 predicted cooperative TF pairs shows that our method has the power to
      find cooperative TF pairs of different biological processes. CONCLUSION: Our
      method is effective in identifying cooperative TF pairs in yeast. Many of our
      predictions are validated by the literature, and our method outperforms 11
      existing methods. We believe that our study will help biologists to understand
      the mechanisms of transcriptional regulation in eukaryotic cells.

PMID- 25559500
TI  - Resolution and chiral recognition of muscone as well as actions on neural system.
AB  - In this letter, (R)-muscone and (S)-muscone were prepared by optical resolution
      of dl-muscone using N,N'-dibenzyl-l-tartaramide or N,N'-dibenzyl-d-tartaramide,
      according to the method reported by Kunihiko Takabe. But we separated the
      diastereomers using EtOH instead of MeOH in the recrystallization step to get the
      goal product with higher optical purity and yield. The regulatory effect of
      muscone and its enantiomer on the neural system showed that they could prolong
      mouse hypoxia tolerance and dose-dependently enhance mouse spinal cord
      stimulation induced by strychnine nitrate. (R)-muscone and (S)-muscone had a
      synergistic action on shortening sleep time induced by sodium pentobarbital in
      mice. 

PMID- 25559501
TI  - Sexual desire, not hypersexuality, predicts self-regulation of sexual arousal.
AB  - A person's ability to control their own sexual arousal is important both to
      reduce the risks associated with some sexual behaviours and to respond sexually
      with intimate partners. A lack of control over sexual urges is a proposed feature
      of "hypersexual disorder", though some evidence suggests that sexual desire
      predicts the self-regulation of sexual arousal better than hypersexuality. In the
      current study, a sample (N = 116) of men and women recruited from community ads
      viewed a series of 20-second neutral and sexual films. Before each sexual film,
      participants were instructed to increase their sexual arousal, decrease their
      sexual arousal or respond as usual. Higher levels of desire for sex with a
      partner consistently predicted failures to downregulate sexual arousal.
      Hypersexuality was unrelated. These findings replicate Winters et al.'s study and
      extend their findings by including upregulation, women, a new measure of
      hypersexuality and a higher-trial design. 

PMID- 25559502
TI  - Fractalkine promotes chemotaxis of bone marrow-derived mesenchymal stem cells
      towards ischemic brain lesions through Jak2 signaling and cytoskeletal
      reorganization.
AB  - The fractalkine (FKN)-CX3CR1 (FKN receptor) axis reportedly plays an important
      role in the progression of many neural pathologies. However, its role in the
      recruitment of bone marrow-derived progenitor cells for neurogenesis remains
      elusive. The chemokine-based mechanism underlying the migration of bone marrow
      derived mesenchymal stem cells (BMSCs) was investigated in a double-chamber
      transmigration model with recombinant FKN and endogenous FKN extract, and the
      results confirmed the involvement of FKN in migration. This chemotactic response
      was CX3CR1-dependent and FKN-sensitive. Western blotting, immunoprecipitation and
      transmigration assays revealed that the Janus kinase (Jak)2-signal transducer and
      activator of transcription (Stat)5alpha-extracellular signal-related kinase
      (ERK)1/2 pathway was activated by FKN. Confocal laser scanning microscopy was
      used to demonstrate cytoskeletal reorganization caused by remodeling of the
      surface receptor integrin alpha5beta1, intracellular phosphorylation of Fak and
      Pax, and upregulation of intercellular adhesion molecule-1 during BMSC migration.
      Moreover, significant inhibition of signaling and migration was detected after
      treatment of cells with Jak2-interfering RNA or the antagonist AG490. In
      addition, the results of a fluorescence immunohistochemical analysis of an in
      vivo chemotactic model, developed via transplantation of BMSCs into transient
      middle cerebral artery-occluded rats, were consistent with the in vitro results.
      These findings suggest that FKN activates Jak2-Stat5alpha-ERK1/2 signaling
      through CX3CR1, thereby triggering integrin-dependent machinery reorganization to
      allow chemotactic migration of BMSCs towards an ischemic cerebral lesion.

PMID- 25559503
TI  - Geographic atrophy: clinical impact and emerging treatments.

PMID- 25559504
TI  - Optical coherence tomography measurements of choroidal thickness in healthy eyes:
      correlation with age and axial length.
AB  - BACKGROUND AND OBJECTIVE: To evaluate subfoveal choroidal thickness (CT) in
      healthy eyes using spectral-domain optical coherence tomography (SD-OCT) and
      provide correlations between age and axial length. PATIENTS AND METHODS: Enhanced
      depth SD-OCT imaging was performed with Cirrus (Carl Zeiss Meditec, Dublin, CA)
      and Spectralis (Heidelberg Engineering, Heidelberg, Germany) instruments. CT was
      measured from the outer limit of the retinal pigment epithelium to the inner
      surface of the sclera. RESULTS: The study enrolled 155 patients, with at least 20
      in each decade between 22 and 89 years old. Mean axial length was 23.6 mm. Mean
      Heidelberg subfoveal CT was 286 um. The correlation between Heidelberg and Zeiss
      subfoveal CT measurements was strong (r = .978) and significant (P < .001). Mean
      subfoveal CT was 7.7 um thinner by Heidelberg versus Cirrus (P < .001). Multiple
      linear regression analysis revealed that age (P < .001), axial length (P = .001),
      and sex (P = .025) were significantly related to Heidelberg subfoveal CT.
      CONCLUSION: There is a strong negative correlation between CT and age (P <.001),
      with a 25 um decrease in CT for each decade of life. Increasing axial length
      demonstrated a negative correlation with CT, decreasing 24.9 um for each mm of
      axial length. Future studies of CT measurements can be performed on either
      instrument and must account for axial length, age, and sex to make appropriate
      conclusions.

PMID- 25559505
TI  - Choroidal thickness and choroidal blood flow after intravitreal bevacizumab
      injection in eyes with central serous chorioretinopathy.
AB  - BACKGROUND AND OBJECTIVE: To quantitatively evaluate choroidal thickness (CT) and
      choroidal blood flow in the subfoveal region after intravitreal bevacizumab
      injection (IVB) for the treatment of chronic central serous chorioretinopathy
      (CSC). PATIENTS AND METHODS: Prospective, comparative study of 20 eyes with
      chronic CSC and and 20 fellow eyes treated with 1.25 mg/0.05 mL IVB. Subfoveal CT
      and serous retinal detachment height were measured using enhanced depth imaging
      optical coherence tomography. Subfoveal choroidal blood flow was assessed by the
      mean blur rate of laser speckle flowgraphy. IOP, blood pressure, and pulse rate,
      and ocular perfusion pressure were also measured. All measurements were made
      before and after IVB. RESULTS: Subfoveal fluid was not present after IVB in the
      affected eyes. The mean subfoveal CT decreased from 335 um at baseline to 304 and
      291 um at 1 and 3 months, respectively, after IVB. Average mean blur rate ratio
      decreased from baseline to 92.9% and 88.0% at 1 and 3 months, respectively. In
      the fellow eyes, subfoveal CT and choroidal blood flow decreased slightly from
      baseline. There was a significant correlation between the decrease in subfoveal
      CT and choroidal blood flow after IVB in affected eyes. IOP, mean arterial
      pressure, pulse rate, and ocular perfusion pressure did not change significantly
      after IVB. CONCLUSION: IVB significantly reduced subfoveal CT, choroidal blood
      flow, and subretinal fluid absorption in eyes with chronic CSC. The reduction of
      subfoveal CT after IVB was likely caused by the reduction of subfoveal choroidal
      blood flow.

PMID- 25559506
TI  - Choroidal thickness in macular holes: a case-control study.
AB  - BACKGROUND AND OBJECTIVE: To evaluate choroidal thickness of patients with
      unilateral full-thickness macular holes (FTMHs) and contralateral vitreomacular
      adhesion (VMA) and healthy eyes. PATIENTS AND METHODS: A retrospective case
      control study of patients with unilateral FTMH and contralateral VMA and matched
      healthy controls was performed. Choroidal thickness was measured at five
      locations (subfoveal and 1 mm and 2 mm from the center of the fovea nasally and
      temporally) and compared between groups. RESULTS: Nineteen case patients and 19
      control patients were analyzed. Eyes with FTMH had thinner choroids compared with
      the contralateral eyes with VMA and the control eyes at all locations except 2 mm
      temporal from the fovea. Eyes with VMA had thinner choroids nasally from the
      fovea compared with control eyes. CONCLUSION: Choroidal thickness was
      significantly decreased in eyes with FTMH except at 2 mm temporal to the fovea
      and decreased in contralateral eyes with VMA in the nasal directions, suggesting
      an association between choroidal thinning and macular hole.

PMID- 25559507
TI  - Retrospective comparisons of vitrectomy with and without air tamponade to repair
      lamellar macular hole.
AB  - BACKGROUND AND OBJECTIVE: To investigate the surgical outcomes of vitrectomy with
      to that without air tamponade in eyes with a lamellar macular hole. PATIENTS AND
      METHODS: The medical records of 23 eyes that underwent 25-gauge vitrectomy with
      air tamponade and 18 eyes that underwent 25-gauge vitrectomy alone were reviewed.
      RESULTS: The pre- and postoperative best corrected visual acuities (BCVAs) in
      logarithm of the minimum angle resolution units were 0.26 +/- 0.27 and 0.12 +/-
      0.15 in eyes with tamponade and 0.35 +/- 0.30 and 0.14 +/- 0.23 in eyes without
      tamponade. There were no significant differences in BCVAs between the two groups
      both pre- and postoperatively. Postoperative BCVA was significantly improved in
      eyes with tamponade (P = .023) and without tamponade (P < .001). None of the
      cases developed a full-thickness macular hole postoperatively. CONCLUSION: These
      results suggest that air tamponade may not be required during vitrectomy to
      achieve good BCVA and anatomic closure in eyes with a lamellar macular hole.

PMID- 25559508
TI  - Recovery of photoreceptor layer on spectral-domain optical coherence tomography
      after vitreous surgery combined with air tamponade in chronic idiopathic macular
      hole.
AB  - BACKGROUND AND OBJECTIVE: Studies using sterilized air in chronic idiopathic
      macular holes show varying success rates, and the impact of a shorter duration of
      tamponade on photoreceptor layer recovery is not fully elucidated. PATIENTS AND
      METHODS: Surgical outcomes of 35 cases (seven in stage 3 and 28 in stage 4) were
      assessed for best corrected visual acuity and with spectral-domain optical
      coherence tomography. RESULTS: The primary closure rate was 91.4%, and the closed
      cases and unclosed cases were significantly different in the preoperative (P =
      .042) and postoperative (P = .040) diameter of the photoreceptor layer defect.
      After surgery, there was a significant improvement in best corrected visual
      acuity and a decrease in the photoreceptor layer defect. The postoperative
      logarithm of the minimal angle of resolution was significantly correlated with
      the preoperative hole diameter (P = .003) and the postoperative diameter of the
      photoreceptor layer defect (P = .005). CONCLUSION: Air tamponade is a safe and
      effective treatment for chronic and severe macular holes, with several spectral
      domain optical coherence tomography parameters highly predictive of postoperative
      visual acuity.

PMID- 25559509
TI  - Retina evaluation with nonmydriatic ultrawide-field color imaging after cataract
      extraction surgeries in asymptomatic patients.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the role of nonmydriatic ultrawide-field
      (UWF) color retinal imaging as a screening tool in the follow-up of asymptomatic
      patients after cataract extraction surgeries. PATIENTS AND METHODS: A
      retrospective, observational case series. A review of electronic medical records
      identified patients after cataract extraction followed with UWF retinal imaging
      (Optos 200Tx; Optos, Dunfermline, Scotland). Images were graded and reviewed by a
      retina specialist. Outcome measures included image quality, the detection of
      peripheral lesions, and association with perioperative risk factors. RESULTS:
      Seventy-six eyes of 58 consecutive patients were enrolled. A good visualization
      of the peripheral retina was accomplished in more than 90% of patients.
      Peripheral lesions were identified in 40 eyes (52.6%) with no surgery-related
      retinal breaks and/or detachments. Additional pathologies were found in 35 eyes
      (46.1%). CONCLUSION: Nonmydriatic UWF color retinal imaging was found to be a
      useful screening tool in the follow-up of asymptomatic patients after cataract
      extraction in this series.

PMID- 25559510
TI  - Dexamethasone intravitreal implant for pseudophakic cystoid macular edema in
      patients with diabetes.
AB  - BACKGROUND AND OBJECTIVE: Diabetic patients are at a higher risk of developing
      pseudophakic cystoid macular edema (PCME) after cataract surgery. This study
      evaluated the effect of dexamethasone intravitreal implant (DEX Implant 0.7 mg,
      Ozurdex; Allergan, Irvine, CA) in diabetic patients with PCME. PATIENTS AND
      METHODS: In this prospective case series, six patients with diabetes who
      developed PCME despite topical anti-inflammatory therapy were treated with a
      single dexamethasone implant. Outcome measures included best corrected visual
      acuity (BCVA) and central subfoveal thickness. RESULTS: The mean increase in BCVA
      from baseline to day 180 was 14 letters (P = .03); four of six patients (67%)
      achieved greater than 10-letter improvement in BCVA. The mean decrease in central
      subfoveal thickness was 100 um (P < .01 vs baseline) by day 30 and 72 um by day
      180 (P = .004). CONCLUSIONS: A dexamethasone implant may be an effective
      treatment for diabetic patients who develop pseudophakic cystoid macular edema
      after cataract surgery.

PMID- 25559511
TI  - Cost comparison of intravitreal aflibercept with bevacizumab and ranibizumab for
      the treatment of wet age-related macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: To test the hypothesis that although intravitreal
      aflibercept (IVA) is expected to be more expensive, the extra cost of treatment
      would not result in additional vision gain compared with intravitreal bevacizumab
      (IVB) for the treatment of wet age-related macular degeneration (AMD). PATIENTS
      AND METHODS: A retrospective chart review of patients receiving IVB or
      intravitreal ranibizumab (IVR) who were subsequently changed to IVA for active
      wet AMD. RESULTS: Thirty-three eyes were included in the study. The mean number
      of IVB, IVR, and IVA injections per eye over a 6-month period was seven, six, and
      five, respectively. Visual outcomes were similar in all three groups at the end
      of the study period. The average drug cost of IVB, IVR, and IVA injections per
      eye over 6 months was $326, $11,400, and $9,720, respectively. CONCLUSION:
      Aflibercept may allow a modest extension of the treatment interval, but cost
      makes IVA an expensive alternative without a visual benefit compared with IVB in
      patients with active wet AMD.

PMID- 25559512
TI  - Fluidics comparison between dual pneumatic and spring return high-speed
      vitrectomy systems.
AB  - BACKGROUND AND OBJECTIVE: To compare the water and vitreous flow rates and duty
      cycle (DC) between two ultrahigh-speed vitrectomy systems: pneumatic with spring
      return (SR) and dual pneumatic (DP) probes. MATERIALS AND METHODS: The flow rate
      was calculated using a high-sampling precision balance that measured the mass of
      water and vitreous removed from a vial by a vitreous cutter. Frame-by-frame
      analysis of a high-speed video of the cutter was used to determine the DC. Three
      cutters of each gauge (20, 23, and 25 G) were tested with an SR and a DP system
      using the standard DC setting (biased open) at 0 (water only), 1,000, 2,000,
      3,000, 4,000, and 5,000 cuts per minute (CPM) with aspiration levels of 100, 200,
      300, 400, 500, and 600 mm Hg. RESULTS: The DC was slightly higher with the SR
      system using most parameters and gauges although without statistical
      significance. The water flow rate was somewhat higher with the SR system, except
      for 25 G with 4,000 and 5,000 CPM. The vitreous flow rate was similar using most
      parameters, with the SR system showing higher flows at lower cut rates (1,000
      3,000 CPM). CONCLUSIONS: SR and DP systems produced similar water and vitreous
      flow rates. Additional studies in human eyes are necessary to confirm these
      findings.

PMID- 25559513
TI  - Trimanual technique using assistant-controlled light probe illumination and wide
      angle viewing system in 23-gauge sutureless vitrectomy for diabetic tractional
      retinal detachment.
AB  - BACKGROUND AND OBJECTIVE: The authors propose a novel trimanual vitreous surgery
      using assistant-adjusted endoillumination during 23-gauge sutureless vitrectomy
      for severe diabetic tractional retinal detachment (TRD) under noncontact wide
      angle viewing system. MATERIALS AND METHODS: The trimanual sutureless vitrectomy
      under a wide-angle viewing system consisted of (1) a fourth-port microcannula in
      the inferior 6-o'clock position; (2) dynamic and specular illumination by an
      assistant-controlled light probe inserted through the fourth port; and (3)
      membrane dissection and bleeding control using two intraocular instruments.
      RESULTS: Six eyes of four patients who underwent trimanual diabetic vitrectomy
      were evaluated. Recurrent TRD was detected in one eye, and a second operation was
      performed. There were no intraoperative sclerotomy-related complications or
      postoperative hypotony, increased IOP, or endophthalmitis. Final anatomic and
      functional success was achieved in all six eyes. CONCLUSION: The trimanual
      technique is valuable for membrane dissection in severe diabetic TRD. The optimal
      and dynamic illumination provided a high-quality stereoscopic view under a wide
      angle viewing system. Careful coordination between a surgeon and an assistant
      facilitates this technique.

PMID- 25559514
TI  - Visual recovery and OCT evolution following central retinal artery occlusion
      treated with intra-arterial verapamil and alteplase infusion.
AB  - A 69-year-old woman presented with a "veil" over the left eye. Clinical
      examination demonstrated signs of central retinal artery occlusion. Visual acuity
      was compromised to 1/200 E in the left eye. Ocular massage and anterior chamber
      paracentesis failed to improve vision. An emergent intra-arterial catheterization
      with verapamil and alteplase infusion was performed less than 12 hours following
      symptom onset. Initial optical coherence tomography (OCT) showed inner retinal
      edema. One year later, OCT revealed relatively minor thinning, which could
      explain the patient's visual recovery to 20/40. This may be the first article to
      report OCT changes following this treatment for central retinal artery occlusion.

PMID- 25559515
TI  - Treatment of cytomegalovirus retinitis with cytomegalovirus-specific T-lymphocyte
      infusion.
AB  - Cytomegalovirus (CMV) retinitis is a potentially blinding infection that affects
      immunocompromised patients who are unable to generate a T-cell response against
      the organism. Infusion of CMV-specific leukocytes has been shown to be effective
      in patients with systemic CMV infection, especially those resistant to standard
      therapies. The authors report a case of a patient with CMV viremia with
      progressive retinitis in whom infusion of third-party donor-derived CMV pp65
      specific T cells alone prompted resolution of CMV retinitis. This case suggests a
      potential role for CMV-specific leukocyte infusion in the treatment of CMV
      retinitis, especially in cases resistant or refractory to antiviral therapies.

PMID- 25559516
TI  - Regression of macular drusenoid retinal pigment epithelial detachments after
      plaque radiation therapy.
AB  - The authors describe a case in which drusenoid retinal pigment epithelial
      detachments (DRPEDs) melted after plaque radiation therapy for an unrelated
      choroidal melanoma. The patient had a history of bilateral macular DRPEDs prior
      to palladium-103 plaque therapy. The choroidal melanoma was located in the
      temporal macula. The central fovea was calculated to receive an incidental
      radiation dose of 34 Gy. Six months after treatment, an ipsilateral, unilateral
      reduction of DRPEDs was first noted by comparative fundus photography and optical
      coherence tomography. From his initial evaluation to his last follow-up, the
      patient's visual acuity slightly improved from 20/20 to 20/16.

PMID- 25559517
TI  - Retinal pigment epithelial tear after intravitreal aflibercept for neovascular
      age-related macular degeneration.
AB  - Two eyes with neovascular age-related macular degeneration and a suboptimal
      response to intravitreal ranibizumab and bevacizumab developed tears after being
      switched to intravitreal aflibercept, a drug with enhanced binding
      characteristics to vascular endothelial growth factor. Both eyes had sub-retinal
      pigment epithelium (RPE) choroidal neovascularization adherent to the back
      surface of the RPE in the fibrovascular RPE detachment that showed increased
      contracture of the fibrovascular tissue following the use of aflibercept. The
      driving force to develop the tears may be related to the recently described
      angiofibrotic switch, which is governed by the ration of connective tissue growth
      factor to vascular endothelial growth factor.

PMID- 25559518
TI  - Intravitreal injection of ziv-aflibercept in patient with refractory age-related
      macular degeneration.
AB  - The results of a patient with exudative age-related macular degeneration who
      received an intravitreal injection of ziv-aflibercept (Zaltrap; Sanofi-Aventis,
      Paris, France) in the right eye are described. A complete ocular examination as
      well as color fundus photography, optical coherence tomography, fluorescein
      angiography, microperimetry, full-field electroretinography, and multifocal
      electroretinography were performed and repeated 1 month later. The patient
      experienced subjective and objective improvement of visual acuity with a decrease
      in intraretinal and subretinal fluid. Microperimetric improvement also occurred.
      Electroretinographic changes were noted from baseline to the 30-day follow-up. No
      adverse events were observed at any time point. Ziv-aflibercept demonstrated
      short-term safety and efficacy after intravitreal administration for neovascular
      macular degeneration.

PMID- 25559519
TI  - Bevacizumab in macular serous detachments associated with Waldenstrom's
      macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia (WM) is a lymphoproliferative B-cell disorder
      characterized by monoclonal proliferation of immunoglobulin M. WM can be
      associated with impressive hyperviscosity retinopathy and a unique tendency to
      develop serous macular detachments. These have been described as immunogammopathy
      maculopathy and portend a poor visual prognosis, often persisting despite
      multiple plasmapheresis treatments. In this case report, the authors demonstrate
      the accelerated resolution of hyperviscosity retinopathy and associated macular
      detachments in a patient with WM with marked visual improvement. This case report
      serves to raise awareness of the potential role of anti-vascular endothelial
      growth factor modulation in the treatment of patients with hyperviscosity
      retinopathy associated with WM.

PMID- 25559520
TI  - Oral rifampin for central serous retinopathy: a strategic approach in three
      patients.
AB  - The authors present three cases of chronic central serous retinopathy in which
      rifampin was used for the utility of its oral delivery in remote care and as an
      alternative to photodynamic therapy when intravenous access was not possible. In
      each of these cases, a reduction of subfoveal fluid and improvement of visual
      acuity were achieved.

PMID- 25559521
TI  - Inner segment ellipsoid layer restoration after macula-off rhegmatogenous retinal
      detachment.
AB  - Spectral-domain optical coherence tomography (SD-OCT) often reveals prominent
      outer retinal changes after macula-off rhegmatogenous retinal detachment. Two
      patients who presented with macula-off retinal detachment underwent surgical
      repair. Initial postoperative visual acuity was 20/200 in both cases and
      correlated with a disruption of the central inner segment ellipsoid layer on SD
      OCT. On extended follow-up, SD-OCT demonstrated restoration of the inner segment
      ellipsoid layer in both patients with concurrent improved visual acuity.

PMID- 25559522
TI  - Vitrectomy without gas tamponade for macular retinoschisis associated with normal
      tension glaucoma.
AB  - The authors present the case of a patient with normal-tension glaucoma and pit
      like maculopathy observed by high-definition optical coherence tomography.
      Surgical management of macular retinoschisis was associated with improved vision
      and full resolution of intraretinal fluid and macular detachment. The patient had
      progressive vision loss over 6 months preoperatively; best corrected visual
      acuity and high-definition optical coherence tomography changes improved
      postoperatively. Optic disc pit-like maculopathy can occur in patients with
      normal-tension glaucoma in the absence of obvious congenital anomalies of the
      disc. The intraretinal fluid might have migrated from the vitreous cavity through
      a microhole at the optic disc margin or in the area with the nerve fiber defect.
      Vitrectomy without gas tamponade might lead to anatomic and functional recovery.
      Further studies are needed to better understand the pathogenesis of this disease.

PMID- 25559523
TI  - Ghost cell glaucoma following sutureless scleral-fixated posterior chamber
      intraocular lens placement.
AB  - Secondary intraocular lens (IOL) placement in the absence of a capsular bag may
      result in several complications. The authors report the clinicopathologic
      features of a case of ghost cell glaucoma after the placement of a sutureless
      posterior chamber IOL. A 47-year-old male presented with a dislocated IOL and
      underwent lens exchange using a sutureless scleral-fixation technique. Over the
      following year, the patient developed recurrent vitreous hemorrhages and elevated
      intraocular pressure despite medical therapy, and an aqueous specimen disclosed
      ghost cells. Although uncommon, mechanical contact between the iris and a
      secondary IOL may produce persistent vitreous hemorrhage and elevated intraocular
      pressures with the formation of ghost cells.

PMID- 25559524
TI  - Acute macular neuroretinopathy: a case report and review of the literature, 2002
      2012.
AB  - Acute macular neuroretinopathy (AMNR) is a rare condition that primarily affects
      young women in their reproductive years. Many of the affected young women are on
      oral contraceptives. Patients report a sudden decrease in visual acuity, usually
      a few days after the onset of a febrile illness, with paracentral scotomas either
      unilaterally or bilaterally. Although AMNR was initially thought to be an inner
      retinal pathology, with the publication of 84 case reports in the English medical
      literature and the advent of new imaging modalities, it is now thought to be a
      disease of the outer retina. In 2003, Turbeville et al published a review of more
      than 41 AMNR cases reported from 1975 to March 2002, which summarized the
      available literature and suggested potential fields of research to be explored.
      This article summarizes the 43 case reports that were published in the English
      literature from April 2002 to October 2012 and also presents a unique case of
      AMNR.

PMID- 25559525
TI  - Natural course of symptomatic focal choroidal excavation.
AB  - A 32-year-old man was referred to the authors' department for nonspecified
      macular dystrophy with persistent metamorphopsia in the right eye diagnosed 10
      years before and followed using optical coherence tomography. The patient
      underwent a comprehensive ocular examination, including multimodal imaging
      evaluation and electrofunctional testing. The diagnosis was consistent with
      nonconforming focal choroid excavation. Over 10 years, no complications occurred,
      visual acuity was stable, and optical coherence tomography showed no progression
      of the lesion during follow-up. In this case, nonconforming symptomatic focal
      choroid excavation was a nonprogressive condition with good long-term visual
      outcome.

PMID- 25559526
TI  - Stability of macular traction in involutional diabetic retinopathy over a 5-year
      course.
AB  - Involutional diabetic retinopathy is a descriptive term for an end-stage phase of
      proliferative diabetic retinopathy (PDR), which is often non-progressive. Two
      patients with involutional PDR with nonprogressive macular traction documented by
      spectral-domain optical coherence tomography (SD-OCT) over a 5-year period are
      described in this report.

PMID- 25559527
TI  - A novel clinical sign in macular telangiectasia type 2.
AB  - The objective of the study is to report, and propose a hypothesis for, a novel
      clinical sign in patients with macular telangiectasia type 2. Nine consecutive
      patients with macular telangiectasia and visible parafoveal graying were
      examined. The parafoveal graying decreased in intensity with continuous light
      exposure from an indirect ophthalmoscope. After dark adaptation for 15 minutes,
      the intensity of parafoveal graying increased again. This phenomenon appears to
      be a novel and global sign in patients with macular telangiectasia type 2. It
      could be a possible photochemical reaction occurring due to the release of
      chromophores from the abnormal Muller cells.

PMID- 25559528
TI  - The role of intravitreal trimethoprim/sulfamethoxazole in the treatment of
      toxoplasma retinochoroiditis.
AB  - The authors evaluate the role of intravitreal trimethoprim/sulfamethoxazole in
      the treatment of toxoplasma retinochoroiditis (TRC) in four patients.
      Intravitreal injection of trimethoprim/sulfamethoxazole 1.28 mg/0.08 mL with
      dexamethasone 400 ug/0.1 mL was injected weekly or biweekly. After the initiation
      of treatment, a reduction in intraocular inflammation was observed clinically and
      on optical coherence tomography within 1 week. Three patients regained visual
      acuity of 20/20, and one patient improved to 20/40 with residual macular
      scarring. No evidence of retinal toxicity was noted on full-field
      electroretinogram. Intravitreal trimethoprim/sulfamethoxazole and dexamethasone
      combination may be an alternative treatment strategy in patients with TRC.

PMID- 25559529
TI  - Paul Sullivan: catalyst in the history and use of intraocular sulfur
      hexafluoride.
AB  - The use of air to attempt to reattach the retina dates back to 1909. However,
      despite the widespread use of intraocular air in the 1950s and 1960s, retinal
      surgeons struggled with the main limitation of the device (ie, the relatively
      short duration of the gas within the vitreous cavity). Fortuitous events in the
      late 1960s allowed Paul Sullivan, MD, to introduce the first expansile gas,
      sulfur hexafluoride, to Edward W.D. Norton, MD, and his colleagues at the
      University of Miami. The use of sulfur hexafluoride helped revolutionize retinal
      detachment surgery and allowed for further advances in treating other posterior
      segment diseases.

PMID- 25559530
TI  - 8 Questions with Dr. Puliafito.

PMID- 25559531
TI  - Continuing the JCEM mission with its new editorial team.

PMID- 25559533
TI  - Retractions.

PMID- 25559536
TI  - Letter to the editor: methodological approach to paraoxonase-1 activity in
      obesity complicated by obstructive sleep apnea.

PMID- 25559537
TI  - Response letter to the editor.

PMID- 25559538
TI  - Letter to the editor: recent advances in genetic testing and treatment of
      neonatal diabetes mellitus.

PMID- 25559539
TI  - Response letter to the editor.

PMID- 25559540
TI  - Letter to the editor: MU-crystallin/CRYM functions as a ketimine-reducing enzyme
      and plays a role in thyroid hormone bioavailability due to strong
      inhibition/regulation by thyroid hormones.

PMID- 25559541
TI  - Response to letter to the editor.

PMID- 25559542
TI  - Letter to the editor: Dubowitz syndrome: a unique clinical disorder that is often
      confused with Bloom syndrome.

PMID- 25559543
TI  - Letter to the editor: a biochemical view: incidence of hypocalcemic seizures due
      to vitamin D deficiency in children in the United Kingdom & Ireland.

PMID- 25559544
TI  - Response letter to the editor.

PMID- 25559545
TI  - Letter to the editor: denosumab for "resistant" hypercalcemia in patients with
      impaired renal function.

PMID- 25559546
TI  - Response letter to the editor.

PMID- 25559547
TI  - Letter to the editor.

PMID- 25559548
TI  - Response letter to the editor.

PMID- 25559549
TI  - Obscure gastrointestinal bleeding: diagnosis and treatment.
AB  - Small-bowel bleeding comprises a majority of obscure gastrointestinal bleeding,
      but is caused by various kinds of diseases. For its diagnosis, history-taking and
      physical examination is requisite, leading to a suspicion of what diseases are
      involved. Next, cross-sectional imaging such as computed tomography should be
      done, followed by the latest enteroscopy, videocapsule endoscopy and deep
      enteroscopy according to the severity of hemorrhage and patient conditions. After
      comprehensive diagnosis, medical, enteroscopic, or surgical treatment should be
      selected. 

PMID- 25559551
TI  - Introducing conformal prediction in predictive modeling for regulatory purposes.
      A transparent and flexible alternative to applicability domain determination.
AB  - Conformal prediction is presented as a framework which fulfills the OECD
      principles on (Q)SAR. It offers an intuitive extension to the application of
      machine-learning methods to structure-activity data where focus is on predictions
      with pre-defined confidence levels. A conformal predictor will make correct
      predictions on new compounds corresponding to a user defined confidence level.
      The confidence level can be altered depending on the situation the predictor is
      being used in, which allows for flexibility and adaption to risks that the user
      is willing to take. We demonstrate the usefulness of conformal prediction by
      applying it to 2 publicly available CAESAR binary classification datasets. 

PMID- 25559550
TI  - Symptom burden in community-dwelling older people with multimorbidity: a cross
      sectional study.
AB  - BACKGROUND: Globally, the population is ageing and lives with several chronic
      diseases for decades. A high symptom burden is associated with a high use of
      healthcare, admissions to nursing homes, and reduced quality of life. The aims of
      this study were to describe the multidimensional symptom profile and symptom
      burden in community-dwelling older people with multimorbidity, and to describe
      factors related to symptom burden. METHODS: A cross-sectional study including 378
      community-dwelling people >= 75 years, who had been hospitalized >= 3 times
      during the previous year, had >= 3 diagnoses in their medical records. The
      Memorial Symptom Assessment Scale was used to assess the prevalence, frequency,
      severity, distress and symptom burden of 31 symptoms. A multiple linear
      regression was performed to identify factors related to total symptom burden.
      RESULTS: The mean number of symptoms per participant was 8.5 (4.6), and the mean
      total symptom burden score was 0.62 (0.41). Pain was the symptom with the highest
      prevalence, frequency, severity and distress. Half of the study group reported
      the prevalence of lack of energy and a dry mouth. Poor vision, likelihood of
      depression, and diagnoses of the digestive system were independently related to
      the total symptom burden score. CONCLUSION: The older community-dwelling people
      with multimorbidity in this study suffered from a high symptom burden with a high
      prevalence of pain. Persons with poor vision, likelihood of depression, and
      diseases of the digestive system are at risk of a higher total symptom burden and
      might need age-specific standardized guidelines for appropriate management.

PMID- 25559552
TI  - Use of the temporal median and trimmed mean mitigates effects of respiratory
      motion in multiple-acquisition abdominal diffusion imaging.
AB  - Respiratory motion commonly confounds abdominal diffusion-weighted magnetic
      resonance imaging, where averaging of successive samples at different parts of
      the respiratory cycle, performed in the scanner, manifests the motion as blurring
      of tissue boundaries and structural features and can introduce bias into
      calculated diffusion metrics. Storing multiple averages separately allows
      processing using metrics other than the mean; in this prospective volunteer
      study, median and trimmed mean values of signal intensity for each voxel over
      repeated averages and diffusion-weighting directions are shown to give images
      with sharper tissue boundaries and structural features for moving tissues, while
      not compromising non-moving structures. Expert visual scoring of derived
      diffusion maps is significantly higher for the median than for the mean, with
      modest improvement from the trimmed mean. Diffusion metrics derived from mono-
      and bi-exponential diffusion models are comparable for non-moving structures,
      demonstrating a lack of introduced bias from using the median. The use of the
      median is a simple and computationally inexpensive alternative to complex and
      expensive registration algorithms, requiring only additional data storage (and no
      additional scanning time) while returning visually superior images that will
      facilitate the appropriate placement of regions-of-interest when analysing
      abdominal diffusion-weighted magnetic resonance images, for assessment of disease
      characteristics and treatment response. 

PMID- 25559553
TI  - Concordance with World Cancer Research Fund/American Institute for Cancer
      Research (WCRF/AICR) guidelines for cancer prevention and obesity-related cancer
      risk in the Framingham Offspring cohort (1991-2008).
AB  - PURPOSE: This prospective cohort study evaluates associations between healthful
      behaviors consistent with WCRF/AICR cancer prevention guidelines and obesity
      related cancer risk, as a third of cancers are estimated to be preventable.
      METHODS: The study sample consisted of adults from the Framingham Offspring
      cohort (n = 2,983). From 1991 to 2008, 480 incident doctor-diagnosed obesity
      related cancers were identified. Data on diet, measured by a food frequency
      questionnaire, anthropometric measures, and self-reported physical activity,
      collected in 1991 was used to construct a 7-component score based on
      recommendations for body fatness, physical activity, foods that promote weight
      gain, plant foods, animal foods, alcohol, and food preservation, processing, and
      preparation. Multivariable Cox regression models were used to estimate
      associations between the computed score, its components, and subcomponents in
      relation to obesity-related cancer risk. RESULTS: The overall score was not
      associated with obesity-related cancer risk after adjusting for age, sex,
      smoking, energy, and preexisting conditions (HR 0.94, 95 % CI 0.86-1.02). When
      score components were evaluated separately, for every unit increment in the
      alcohol score, there was 29 % lower risk of obesity-related cancers (HR 0.71, 95
      % CI 0.51-0.99) and 49-71 % reduced risk of breast, prostate, and colorectal
      cancers. Every unit increment in the subcomponent score for non-starchy plant
      foods (fruits, vegetables, and legumes) among participants who consume starchy
      vegetables was associated with 66 % reduced risk of colorectal cancer (HR 0.44,
      95 % CI 0.22-0.88). CONCLUSIONS: Lower alcohol consumption and a plant-based diet
      consistent with the cancer prevention guidelines were associated with reduced
      risk of obesity-related cancers in this population.

PMID- 25559555
TI  - Far- and near-field properties of gold nanoshells studied by photoacoustic and
      surface-enhanced Raman spectroscopies.
AB  - Gold nanoshells, with a silica core and different core and shell dimensions, have
      been extensively investigated. Optical far-field properties, namely extinction
      and absorption, have been separately determined by means of spectrophotometry and
      photoacoustic spectroscopy, respectively, in the 440-900 nm range. The
      enhancement factor for surface-enhanced Raman scattering, which is related to
      near-field effects, has been measured from 568 to 920 nm. The absorption
      contribution to extinction decreases as the overall diameter increases. Moreover,
      absorption and scattering display different spectral distributions, the latter
      being red shifted. The Surface Enhanced Raman Scattering enhancement profile,
      measured using thiobenzoic acid as a Raman probe, is further shifted to the red.
      The latter result suggests that the enhancement is dominated by the presence of
      hot spots, which are possibly related to the surface roughness of gold nanoshell
      particles. 

PMID- 25559556
TI  - Incidence of head and neck squamous cell carcinoma among subjects at high risk of
      lung cancer: results from the Pittsburgh Lung Screening Study.
AB  - BACKGROUND: Earlier detection and diagnosis of head and neck squamous cell
      carcinoma (HNSCC) should lead to improved outcomes. However, to the authors'
      knowledge, no effective screening strategy has been identified to date. In the
      current study, the authors evaluated whether it would be useful to screen
      subjects targeted for lung cancer screening for HNSCC as well. METHODS: Medical
      records, death certificates, and cancer registry and questionnaire data were used
      to determine the number of observed incident HNSCC cases in the Pittsburgh Lung
      Screening Study (PLuSS), a cohort of current and former smokers aged >=50 years
      with a >=12.5 pack-year smoking history. The expected number of cases was
      estimated using stratum-specific incidence rates obtained from Surveillance,
      Epidemiology, and End Results data for 2000 through 2011. The standardized
      incidence ratio was calculated to examine the difference between the observed and
      expected number of cases. RESULTS: Of the 3587 at-risk participants in the PLuSS,
      23 (0.64%) developed HNSCC over a total of 32,201 person-years of follow-up. This
      finding was significantly higher than expected based on incidence rates obtained
      from the Surveillance, Epidemiology, and End Results program (13.70 cases
      expected; standardized incidence ratio, 1.68 [95% confidence interval, 1.06
      2.52]). The excess burden of HNSCC in the PLuSS was 28.9 cases per 100,000 person
      years. Observed incident cases were significantly more often male, had started
      smoking at a younger age, smoked more per day, and had more pack-years of smoking
      than the rest of the PLuSS at-risk participants. CONCLUSIONS: The results of the
      current study provide a rationale for offering head and neck cancer screening
      along with computed tomography screening for lung cancer. Randomized controlled
      trials that assess the effectiveness of adding examination of the head and neck
      area to lung cancer screening programs are warranted.

PMID- 25559557
TI  - Biochemical characterization of RecA variants that contribute to extreme
      resistance to ionizing radiation.
AB  - Among strains of Escherichia coli that have evolved to survive extreme exposure
      to ionizing radiation, mutations in the recA gene are prominent and contribute
      substantially to the acquired phenotype. Changes at amino acid residue 276, D276A
      and D276N, occur repeatedly and in separate evolved populations. RecA D276A and
      RecA D276N exhibit unique adaptations to an environment that can require the
      repair of hundreds of double strand breaks. These two RecA protein variants (a)
      exhibit a faster rate of filament nucleation on DNA, as well as a slower
      extension under at least some conditions, leading potentially to a distribution
      of the protein among a higher number of shorter filaments, (b) promote DNA strand
      exchange more efficiently in the context of a shorter filament, and (c) are
      markedly less inhibited by ADP. These adaptations potentially allow RecA protein
      to address larger numbers of double strand DNA breaks in an environment where ADP
      concentrations are higher due to a compromised cellular metabolism. 

PMID- 25559558
TI  - Limbal epithelial stem-microenvironmental alteration leads to pterygium
      development.
AB  - Maintenance of tissue homeostasis relies on the accurate regulation of tissue
      specific stem cell activity which is governed by the dynamic interaction between
      the positive and negative feedback modulating mechanism of stem cell
      microenvironmental niche. Alteration or deregulation of the "stem
      microenvironmental networking" provokes disease development. Limbal epithelial
      stem cells (LESC) are the initiator hierarchy that maintains corneal integrity.
      Compartmentalization of LESC within the limbal vicinity provides an opportunity
      to understand the stem-microenvironmental relationship. The purpose of this study
      was to determine the microenvironmental alteration associated with LESCs fate in
      pterygium condition in comparison with healthy state. Clinical observations
      evaluated the ocular surface disorder with respect to corneal vascularization,
      tear film abnormality, and thickening of limbal area in pterygium patients.
      Structural alteration of limbal stem/progenitor cells and its neighboring niche
      components were observed using histology and scanning electron microscopy.
      Receptor overexpression of TGFbeta-R1, EGF-R1, and IL6-Ralpha and alteration of
      IL2-Ralpha expression pointed toward aberration of "stem-microenvironmental
      networking" in the limbal vicinity during disease development. Increased cell
      proliferation index along with TERT, Cyclin-D1, and PCNA over-expression in
      limbal part of pterygium epithelial cells indicated increased cellular
      proliferation and disturbed homeostatic equilibrium. We postulate that pterygium
      is associated with limbal microenvironmental anomaly where the resident
      epithelial cells became hyperproliferative. 

PMID- 25559559
TI  - 'Do I need to become someone else?' A qualitative exploratory study into the
      experiences and needs of adults with ADHD.
AB  - BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a common
      psychiatric disorder in childhood which has recently been acknowledged to persist
      into adulthood in two-thirds of cases. However, the problems faced by adults with
      ADHD in their daily lives remain largely unexplored. OBJECTIVE: To assess the
      perspectives, problems and needs of adults with ADHD. DESIGN AND PARTICIPANTS: In
      this exploratory qualitative study, adults (n = 52) with a primary ADHD or ADD
      diagnosis, aged 21 years or older, participated in eight focus groups in five
      cities in the Netherlands. RESULTS: Although core symptoms of ADHD were perceived
      as a problem, participants placed greater emphasis on social problems that arise
      from living with ADHD and their subsequent effects on self-image. Accompanying
      problems were feelings of powerlessness, lack of acceptance by their social
      environment and poor self-image. Adults with ADHD would like to see greater
      acceptance of ADHD and its accompanying problems, together with appreciation for
      personal competences and strengths in certain domains, such as creative or
      associative thinking. CONCLUSION: Our study adds to previous research by
      providing insight into how these problems are interrelated and their strong link
      to the social environment. Perceived powerlessness, failure and negative
      reactions of the social environment lead to a persistent low self-image. This
      merits substantial attention in future research, particularly when considering on
      going care options.

PMID- 25559560
TI  - How does yoga reduce stress? A systematic review of mechanisms of change and
      guide to future inquiry.
AB  - Yoga is increasingly used in clinical settings for a variety of mental and
      physical health issues, particularly stress-related illnesses and concerns, and
      has demonstrated promising efficacy. Yet the ways in which yoga reduces stress
      remain poorly understood. To examine the empirical evidence regarding the
      mechanisms through which yoga reduces stress, we conducted a systematic review of
      the literature, including any yoga intervention that measured stress as a primary
      dependent variable and tested a mechanism of the relationship with mediation. Our
      electronic database search yielded 926 abstracts, of which 71 were chosen for
      further inspection and 5 were selected for the final systematic review. These
      five studies examined three psychological mechanisms (positive affect,
      mindfulness and self-compassion) and four biological mechanisms (posterior
      hypothalamus, interleukin-6, C-reactive protein and cortisol). Positive affect,
      self-compassion, inhibition of the posterior hypothalamus and salivary cortisol
      were all shown to mediate the relationship between yoga and stress. It is
      striking that the literature describing potential mechanisms is growing rapidly,
      yet only seven mechanisms have been empirically examined; more research is
      necessary. Also, future research ought to include more rigorous methodology,
      including sufficient power, study randomisation and appropriate control groups. 

PMID- 25559561
TI  - Managers' views on and experiences with moral case deliberation in nursing teams.
AB  - AIMS: Providing management insights regarding moral case deliberation (MCD) from
      the experiential perspective of nursing managers. BACKGROUND: MCD concerns
      systematic group-wise reflection on ethical issues. Attention to implementing MCD
      in health care is increasing, and managers' experiences regarding facilitating
      MCD's implementation have not yet been studied. METHOD: As part of an empirical
      qualitative study on implementing MCD in mental health care, a responsive
      evaluation design was used. Using former research findings (iterative
      procedures), a managers' focus group was organised. RESULTS: Managers appreciated
      MCD, fostering nurses' empowerment and critical reflection - according to
      managers, professional core competences. Managers found MCD a challenging
      intervention, resulting in dilemmas due to MCD's confidential and egalitarian
      nature. Managers value MCD's process-related outcomes, yet these are difficult to
      control/regulate. CONCLUSIONS: MCD urges managers to reflect on their role and
      (hierarchical) position both within MCD and in the nursing team. IMPLICATIONS FOR
      NURSING MANAGEMENT: MCD is in line with transformative and participatory
      management, fostering dialogical interaction between management and nursing team.

PMID- 25559562
TI  - Bi2Te(IO3)O5Cl: a novel polar iodate oxychloride exhibiting a second-order
      nonlinear optical response.
AB  - The novel iodate oxychloride, Bi2Te(IO3)O5Cl, has been hydrothermally synthesized
      and structurally characterized. The compound crystallizes in the polar monoclinic
      space group Cc with a = 22.037(8) A, b = 5.256(2) A, c = 15.142(5) A, and beta =
      104.499(7) degrees . Three types of asymmetric chromophore structural units, that
      is the electron lone-paired [IO3](-) groups, the second-order Jahn-Teller effect
      (SOJT) [BiO6](9-) units, and the distorted [TeO6](6-) octahedra, coexist with
      cooperative dipole moment alignment along the c-axis direction of the crystal.
      This structure configuration gives the material a relatively large second
      harmonic generation (SHG) efficiency of approximately three times that of KDP for
      powder samples. Type I phase-matching at a wavelength of 1064 nm can be achieved
      as a result of the layered structure and large optical anisotropy of the crystal.
      First-principle density functional theory (DFT) calculations were performed to
      interpret relationships between the macroscopic optical properties and
      microscopic structures. The results indicate that the local dipole moments of the
      three types of chromophore units are simultaneously present in the compound with
      different contributions to the SHG effect. Additionally, thermal and optical
      properties of the compound were also characterized. 

PMID- 25559563
TI  - MiR-146b attenuates high-fat diet-induced non-alcoholic steatohepatitis in mice.
AB  - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is one of the most
      common chronic liver diseases worldwide. In this study, we investigated the role
      of miR-146b in the Toll-like receptor-4 signaling pathway and high-fat diet (HFD)
      induced NASH in vivo and in vitro. METHODS: The effect of miR-146b on the
      expression of IL-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor
      receptor-associated factor 6 (TRAF6) in RAW264.7 cells and HepG2 was studied, and
      the effect of miR-146b on lipid accumulation in HepG2 was also studied in vitro.
      The levels of IRAK1, TRAF6, NF-kappaB, and pro-inflammatory cytokines, as well as
      the histologic features and lipid accumulation in the livers of HFD-induced non
      alcoholic steatohepatitis (NASH) and an miR-146b-administered HFD mouse model,
      were studied in vivo. RESULTS: After miR-146b administration, TRAF6 and IRAK1
      mRNA and protein levels in macrophages after lipopolysaccharide administration
      and in HepG2 cells after oleic acid (OA) administration were significantly
      decreased in 146b group compared with control group (P < 0.001). The lipid
      accumulation in HepG2 cells exposed to OA was also decreased by inactivation of
      IRAK1 and TRAF6, then downregulation of the downstream molecules (NF-kappaB) and
      upregulation of the tension homolog deleted on chromosome 10 (PTEN) level. In
      vivo, after administration of miR-146b, TRAF6 and IRAK1 mRNA and protein levels
      as well as TNF-alpha and IL-6 mRNA and protein levels were decreased, and
      hematoxylin and eosin staining showed that the 146b group had low average adipose
      cell cross-sectional areas compared with control group. CONCLUSION: MiR-146b
      ameliorated HFD-induced NASH by directly suppressing IRAK1 and TRAF6.

PMID- 25559564
TI  - [Case management as a methodology for connecting the health and social care
      systems in Spain].
AB  - OBJECTIVE: The aim of this paper is to present the assessment of a case
      management project, implemented with chronic patients in Valencia, for the
      integration of health and social care. This project is linked with the
      'Sustainable Socio-Health Model'. LOCATION: Health department 06 in Valencia.
      PARTICIPANTS: The target groups were chronic patients of 65 years and over.
      INTERVENTIONS: A non-randomized non-blinded comparative study with an
      intervention and control group. The intervention consisted in the creation of an
      interdisciplinary case management team, the use of a common portfolio of
      resources, and its application to a pilot sample with an intervention period of 6
      9 months. MAIN MEASUREMENTS: Diseases (ICD-9), functional capacity, use of health
      and social resources, satisfaction, unit cost services. RESULTS: There was an
      increase in the combined use of health and social resources in the intervention
      group, which included social day centers (21.8% in the intervention group
      compared to 9.8% in the control group), in coordination with primary care
      (suggested as the only health resource in 55.4% of cases). There was a decrease
      in the number of medical visits in the intervention group (43.6% versus 74.5% in
      the control group). Increased patient satisfaction (55.5% in the intervention
      group compared to 29.4% in the control group) was observed. At least an extra
      4.4% of patients were treated using hospital resources without increasing costs.
      CONCLUSIONS: Case management using a common unique portfolio of health and social
      resources can improve the coordination of resources, increases patient
      satisfaction and increases the capacity of using of hospital resources.

PMID- 25559565
TI  - [Attitude of primary care professionals to gender violence. A comparative study
      between Catalonia and Costa Rica].
AB  - OBJECTIVE: Describe the relationship between the attitude towards violence
      against women (VAW) of professionals of the health of primary care with variables
      such professional satisfaction, workload, orientation of professional practice,
      knowledge, training and use of network in Catalonia and Costa Rica. DESIGN: Cross
      exploratory and comparative study. LOCATION: Primary care in Barcelona and nearby
      counties and the Greater Metropolitan Area (GAM) of Costa Rica. PARTICIPANTS: 235
      primary health professionals of Medicine, Nursing, Psychology and Social Work.
      MAIN MEASUREMENTS: Questionnaire with eight sections about attitudes,
      professional satisfaction, and orientation of professional practice, workload,
      knowledge, training and use of network. Three types of analysis were carried out:
      a descriptive one by country; a bivariate analysis; and a multivariable linear
      regression model. RESULTS: Primary Health Professionals attitudes towards VAW
      health were similar in both contexts (Catalonia: 3.90 IC 95% 3.84-3.96; Costa
      Rica: 4.03 IC 95% 3.94-4.13). The variables associated with attitudes towards VAW
      were: Use of network resources (B=0.20, 95% CI -0.14-0.25, P=<.001), Training
      (B=0.10, 95% CI 0.04 to 0.17, P=<0.001), and country, Costa Rica (B=0.16, 95% CI
      0.06 to 0.25, P=<0.001). There was no interaction between the country and the
      other variables, suggesting that the association between the variables and the
      attitude is similar in both countries. CONCLUSIONS: The results suggest that
      increased use of network resources and training are related to a positive
      attitude towards VWA in primary health professionals, both in Catalonia and Costa
      Rica.

PMID- 25559566
TI  - [Development and validation of a questionnaire on knowledge and personal hygiene
      habits in childhood (HICORIN(r))].
AB  - OBJECTIVE: To develop and validate a questionnaire on the integral assessment of
      the habits and knowledge in personal hygiene in children between 7 to 12 years
      old in the educational, social and health environment. DESIGN: Cross-sectional
      study for the validation of a questionnaire. LOCATION: One primary and secondary
      school and one children's home in the Region of Murcia, Spain. PARTICIPANTS: A
      total of 86 children were included (80 from a primary and secondary school; 6
      from a children's home), as well as 7 experts. MAIN MEASUREMENTS: Content
      validation by experts; qualitative assessment; identify difficulties related to
      some questions, item response analysis, and test-retest reliability. RESULTS:
      After the literature search, 20 tools that included items related to child body
      hygiene were obtained. The researchers selected 34 items and drafted 48
      additional ones. After content validity by the experts, the questionnaire
      (HICORIN(r)) was reduced to 63 items, and consisted of 7 dimensions of child
      personal hygiene (skin, hair, hands, oral, feet, ears, and intimate hygiene).
      After with the children some terms were adapted to improve their understanding.
      Only two items had non-response rates that exceeded 10%. The test-retest showed
      that 84.1% of the items had between very good and moderate reliability.
      CONCLUSIONS: HICORIN(r) is a reliable and valid instrument that integrally
      assesses the habits and knowledge in personal hygiene in children between 7-12
      years old. It is applicable in educative and social and health environments and
      in children from different socioeconomic levels.

PMID- 25559567
TI  - The proximal J kappa germline-transcript promoter facilitates receptor editing
      through control of ordered recombination.
AB  - V(D)J recombination creates antibody light chain diversity by joining a Vkappa
      gene segment with one of four Jkappa segments. Two Jkappa germline-transcript
      (GT) promoters control Vkappa-Jkappa joining, but the mechanisms that govern
      Jkappa choice are unclear. Here, we show in gene-targeted mice that the proximal
      GT promoter helps targeting rearrangements to Jkappa1 by preventing premature DNA
      breaks at Jkappa2. Consequently, cells lacking the proximal GT promoter show a
      biased utilization of downstream Jkappa segments, resulting in a diminished
      potential for receptor editing. Surprisingly, the proximal--in contrast to the
      distal--GT promoter is transcriptionally inactive prior to Igkappa recombination,
      indicating that its role in Jkappa choice is independent of classical promoter
      function. Removal of the proximal GT promoter increases H3K4me3 levels at Jkappa
      segments, suggesting that this promoter could act as a suppressor of
      recombination by limiting chromatin accessibility to RAG. Our findings identify
      the first cis-element critical for Jkappa choice and demonstrate that ordered
      Igkappa recombination facilitates receptor editing.

PMID- 25559568
TI  - 2014 clinical practice guidelines for overweight and obesity in Korea.
AB  - The dramatic increase in the prevalence of obesity and its accompanying
      comorbidities are major health concerns in Korea. Obesity is defined as a body
      mass index >=25 kg/m2 in Korea. Current estimates are that 32.8% of adults are
      obese: 36.1% of men and 29.7% of women. The prevalence of being overweight and
      obese in national surveys is increasing steadily. Early detection and the proper
      management of obesity are urgently needed. Weight loss of 5% to 10% is the
      standard goal. In obese patients, control of cardiovascular risk factors deserves
      the same emphasis as weight-loss therapy. Since obesity is multifactorial, proper
      care of obesity requires a coordinated multidisciplinary treatment team, as a
      single intervention is unlikely to modify the incidence or natural history of
      obesity. 

PMID- 25559569
TI  - Antiobesity pharmacotherapy for patients with type 2 diabetes: focus on long-term
      management.
AB  - Type 2 diabetes and obesity have a complex relationship; obesity is linked to
      insulin resistance, the precursor to type 2 diabetes. The management of obesity
      is an important method to delay onset of diabetes and improve the glycemic
      durability of antidiabetic agents. However, insulin and some of the oral
      hypoglycemic agents used to treat diabetes cause significant weight gain, and it
      is difficult for patients with diabetes to reduce and maintain their weight by
      life-style changes alone. Thus, antiobesity medications or bariatric surgery may
      be a necessary adjunct for certain obese patients with diabetes. In 2012, the
      U.S. Food and Drug Administration (FDA) approved lorcaserin and
      phentermine/topiramate extended-release for the management of chronic weight, and
      approval for naltrexone/bupropion sustained-release as an adjunct to exercise and
      reduced caloric intake followed in 2014. Liraglutide is pending FDA approval for
      antiobesity drug. Here we review the efficacy of approved and new promising drugs
      for the management of obesity. 

PMID- 25559570
TI  - Optimal waist circumference cutoff values for the diagnosis of abdominal obesity
      in korean adults.
AB  - Abdominal obesity is associated closely with insulin resistance, diabetes, and
      cardiovascular disease. Waist circumference (WC) is a useful surrogate marker
      commonly used for abdominal adiposity. The determination of WC cutoff levels is
      important in the prevention and treatment of obesity, type 2 diabetes, and
      related cardiovascular diseases. Recent epidemiological evidence suggested that
      appropriate optimal cutoffs for Koreans ranged over 80 to 89.8 cm in males and
      76.1 to 86.5 cm in females. We analyzed the data from two large cohorts using
      receiver operating characteristic curve analysis with the incidences of diabetes,
      hypertension, dyslipidemia, cerebrovascular disease, myocardial infarct, angina,
      coronary artery disease, and multiple metabolic risk factors as outcome
      variables. Optimal WC cutoff points for Koreans were 85 cm in males and 80 cm in
      females. However, considering the prevalence of abdominal obesity and the health
      costs for its prevention and management, 90 cm in males and 85 cm in females are
      probably more appropriate thresholds for abdominal obesity. These values may be
      modified once better research is performed through prospective studies using
      representative populations, common health outcomes, and proper analytical
      approaches. 

PMID- 25559571
TI  - Metabolic and cardiovascular implications of a metabolically healthy obesity
      phenotype.
AB  - Metabolically healthy obesity (MHO) is a new concept in which an individual may
      exhibit an obese phenotype in the absence of any metabolic abnormalities. There
      are a number of definitions of MHO that utilize a variety of components. The
      findings of clinical and basic studies indicate that subjects with MHO do not
      exhibit an increased mortality, an increased risk of cardiovascular disease, or
      an increased risk of type 2 diabetes mellitus, as compared to normal-weight
      controls. Although these findings imply that metabolic health is a more important
      factor than obesity, several studies have shown that subjects with MHO have a
      similar risk of metabolic or cardiovascular diseases as those with metabolically
      unhealthy obesity. Thus, there is still debate regarding not only the
      implications of the MHO phenotype but its very existence. Accordingly, future
      studies should focus on developing a unified definition of MHO and distinguishing
      subjects who will be at a high risk for metabolic and cardiovascular diseases. 

PMID- 25559572
TI  - Roles of protein arginine methyltransferases in the control of glucose
      metabolism.
AB  - Glucose homeostasis is tightly controlled by the regulation of glucose production
      in the liver and glucose uptake into peripheral tissues, such as skeletal muscle
      and adipose tissue. Under prolonged fasting, hepatic gluconeogenesis is mainly
      responsible for glucose production in the liver, which is essential for tissues,
      organs, and cells, such as skeletal muscle, the brain, and red blood cells.
      Hepatic gluconeogenesis is controlled in part by the concerted actions of
      transcriptional regulators. Fasting signals are relayed by various intracellular
      enzymes, such as kinases, phosphatases, acetyltransferases, and deacetylases,
      which affect the transcriptional activity of transcription factors and
      transcriptional coactivators for gluconeogenic genes. Protein arginine
      methyltransferases (PRMTs) were recently added to the list of enzymes that are
      critical for regulating transcription in hepatic gluconeogenesis. In this review,
      we briefly discuss general aspects of PRMTs in the control of transcription. More
      specifically, we summarize the roles of four PRMTs: PRMT1, PRMT 4, PRMT 5, and
      PRMT 6, in the control of hepatic gluconeogenesis through specific regulation of
      FoxO1- and CREB-dependent transcriptional events. 

PMID- 25559573
TI  - Subclinical Cushing's Syndrome and Metabolic Disorder.

PMID- 25559574
TI  - Comparison of serum ferritin and vitamin d in association with the severity of
      nonalcoholic Fatty liver disease in korean adults.
AB  - BACKGROUND: Increased serum ferritin and decreased vitamin D levels associated
      with nonalcoholic fatty liver disease (NAFLD). However, their association with
      the severity of NAFLD has not been fully evaluated. The aim of this study was to
      compare the association of serum ferritin and 25(OH)D3 levels with the severity
      of ultrasonographically detected NAFLD (US-NAFLD) and hepatic steatosis defined
      by fatty liver index (FLI) in Korean adults. METHODS: A cross-sectional analysis
      of clinical and anthropometric data, including serum ferritin and 25(OH)D3, from
      men (n=295) and women (n=263) who underwent a routine health check-up in 2012.
      RESULTS: In men, with an increase in the quartile of serum ferritin level, the
      incidences of subjects with metabolic syndrome (P=0.002), US-NAFLD (P=0.041), and
      FLI >=60 (P=0.010) were significantly elevated. In women, the incidence of
      subjects with US-NAFLD was also significantly elevated with increases in the
      serum ferritin quartile (P=0.012). Regarding 25(OH)D3, no statistical differences
      were observed among the different quartiles in either gender. Serum ferritin
      level significantly increased as the severity of US-NAFLD increased (P<0.001);
      however, no significant differences in 25(OH)D3 level were observed in men. No
      significant differences in either serum ferritin or 25(OH)D3 level were observed
      among women with different levels of severity of US-NAFLD. CONCLUSION: Increased
      serum ferritin level showed a closer association with severity of NAFLD compared
      with level of serum vitamin D, suggesting that serum ferritin level may be a
      better marker than vitamin D level for predicting the severity of US-NAFLD and
      hepatic steatosis in a clinical setting.

PMID- 25559575
TI  - Sex factors in the metabolic syndrome as a predictor of cardiovascular disease.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a condition characterized by a cluster
      of metabolic disorders and is associated with increased risk of cardiovascular
      disease (CVD). This study analyzed data from the Korean Health and Genome Study
      to examine the impact of MetS on CVD. METHODS: A total of 8,898 subjects (4,241
      males and 4,657 females), 40 to 69 years of age, were enrolled and evaluated for
      the development of new onset CVD from 2001 to 2012 (median 8.1 years of follow
      up). RESULTS: The prevalence of MetS at baseline was 22.0% (932/4,241) and 29.7%
      (1,383/4,657) in males and females, respectively. MetS was associated with
      increased risk of coronary heart disease (CHD; hazard ratio [HR], 1.818; 95%
      confidence interval [CI], 1.312 to 2.520 in males; HR, 1.789; 95% CI, 1.332 to
      2.404 in females) and CVD (HR, 1.689; 95% CI, 1.295 to 2.204 in males; HR, 1.686;
      95% CI, 1.007 to 2.192 in females). Specifically, MetS was associated with risk
      of future stroke in females only (HR, 1.486; 95% CI, 1.007 to 2.192). Among MetS
      components, abdominal obesity and hypertension were independent predictors of
      both CHD and CVD. In addition, a higher number of MetS components correlated with
      higher CVD risk. CONCLUSION: MetS is a significant risk factor for the
      development of CVD although its impact varies between sexes.

PMID- 25559576
TI  - Standardized Thyroid Cancer Mortality in Korea between 1985 and 2010.
AB  - BACKGROUND: The prevalence of thyroid cancer has increased very rapidly in Korea.
      However, there is no published report focusing on thyroid cancer mortality in
      Korea. In this study, we aimed to evaluate standardized thyroid cancer mortality
      using data from Statistics Korea (the Statistical Office of Korea). METHODS:
      Population and mortality data from 1985 to 2010 were obtained from Statistics
      Korea. Age-standardized rates of thyroid cancer mortality were calculated
      according to the standard population of Korea, as well as World Health
      Organization (WHO) standard population and International Cancer Survival Standard
      (ICSS) population weights. RESULTS: The crude thyroid cancer mortality rate
      increased from 0.1 to 0.7 per 100,000 between 1985 and 2010. The pattern was the
      same for both sexes. The age-standardized mortality rate (ASMR) for thyroid
      cancer for Korean resident registration population increased from 0.19 to 0.67
      between 1985 and 2000. However, it decreased slightly, from 0.67 to 0.55, between
      2000 and 2010. When mortality was adjusted using the WHO standard population and
      ICSS population weights, the ASMR similarly increased until 2000, and then
      decreased between 2000 and 2010. CONCLUSION: Thyroid cancer mortality increased
      until 2000 in Korea. It started to decrease from 2000.

PMID- 25559577
TI  - Expression of glucagon-like Peptide-1 receptor in papillary thyroid carcinoma and
      its clinicopathologic significance.
AB  - BACKGROUND: Incretin-based therapies are rapidly becoming one of the main
      glycemic control strategies in diabetes. Considering the large numbers of
      papillary thyroid carcinomas (PTCs) and possible effects of glucagon-like peptide
      1 (GLP-1) on cell proliferation, the expression of GLP-1 receptor (GLP-1R) in PTC
      is likely to have clinical significance. We performed this study to evaluate the
      expression of GLP-1R in PTC and the clinical meaning of GLP-1R expression in PTC.
      METHODS: Fifty-six cases of PTC, four cases of medullary thyroid cancer (MTC),
      seven cases of nodular hyperplasia and 56 normal thyroid tissue samples were
      selected for immunostaining for GLP-1R. Clinical parameters were obtained by
      retrospective review of medical records. RESULTS: Immunohistochemical staining
      for GLP-1R showed immunoreactivity in 18 of 56 cases of PTC (32.1%). All four
      cases of MTC exhibited cytoplasmic GLP-1R expression. Nodular hyperplasia
      exhibited immunoreactivity in two of seven cases (28.6%). All normal thyroid
      follicular cells showed negative immunoreactivity. In univariable and
      multivariable analyses, tumor multifocality was negatively correlated with GLP-1R
      expression. Extrathyroidal extension showed positive association with GLP-1R
      expression that was almost significant. Sex, age, tumor size, and lymph node
      metastasis were not significantly associated with GLP-1R expression. CONCLUSION:
      Some parts of PTC tissues express GLP-1R, and GLP-1R expression in PTC was
      negatively correlated with tumor multifocality. The long-term influence of
      pharmacologically increased GLP-1 on thyroid follicular cells and development and
      progression of tumors originating from thyroid follicular cells should be
      investigated.

PMID- 25559578
TI  - Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that
      Chromosome Missegregation Initiates Tumorigenesis.
AB  - BACKGROUND: Aneuploidy has been suggested as one of the major causes of cancer
      from the time of Boveri. In support of this notion, many studies have shown that
      cancer cells exhibit aneuploidy. However, there are evidences that do not support
      the aneuploidy hypothesis. We have previously reported that the spindle assembly
      checkpoint protein BubR1 is acetylated in mitosis and that the acetylation of
      BubR1 is crucial for checkpoint maintenance and chromosome-spindle attachment.
      Mice heterozygous for acetylation-deficient BubR1 (K243R/+) spontaneously develop
      cancer with chromosome instability. As K243R/+ mice develop hepatocellular
      carcinoma, we set out to test if chromosome mis-segregation was the cause of
      their liver cancer. METHODS: Primary hepatocytes in the regenerating liver after
      partial hepatectomy (PH) were analyzed and compared for various mitotic
      parameters. RESULTS: Primary hepatocytes isolated from K243R/+ mice after PH
      displayed a marked increase of chromosome misalignment, accompanied by an
      increase of micronuclei. In comparison, the number of nuclei per cell and the
      centrosome numbers were not different between wild-type and K243R/+ mice. Taken
      together, chromosome mis-segregation provokes tumorigenesis in mouse liver.
      CONCLUSION: Our results corroborate that PH provides a reliable tool for
      assessing mitotic infidelity and cancer in mice.

PMID- 25559579
TI  - Letter: insufficient experience in thyroid fine-needle aspiration leads to
      misdiagnosis of thyroid cancer (endocrinol metab 2014;29:293-9, jung IL son et
      Al.).

PMID- 25559580
TI  - Response: insufficient experience in thyroid fine-needle aspiration leads to
      misdiagnosis of thyroid cancer (endocrinol metab 2014;29:293-9, jung IL son et
      Al.).

PMID- 25559581
TI  - Pharmaceutical, biological, and clinical properties of botulinum neurotoxin type
      A products.
AB  - Botulinum neurotoxin injections are a valuable treatment modality for many
      therapeutic indications and have revolutionized the field of aesthetic medicine
      so that they are the leading cosmetic procedure performed worldwide. Studies show
      that onabotulinumtoxinA, abobotulinumtoxinA, and incobotulinumtoxinA are
      comparable in terms of clinical efficacy. Differences between the products relate
      to the botulinum neurotoxin complexes, specific biological potency, and their
      immunogenicity. Protein complex size and molecular weight have no effect on
      biological activity, stability, distribution, or side effect profile. Complexing
      proteins and inactive toxin (toxoid) content increase the risk of neutralizing
      antibody formation, which can cause secondary treatment failure, particularly in
      chronic disorders that require frequent injections and long-term treatment. These
      attributes could lead to differences in therapeutic outcomes, and, given the
      widespread aesthetic use of these three neurotoxin products, physicians should be
      aware of how they differ to ensure their safe and effective use. 

PMID- 25559582
TI  - Meniscus treatment and age associated with narrower radiographic joint space
      width 2-3 years after ACL reconstruction: data from the MOON onsite cohort.
AB  - OBJECTIVE: To identify risk factors for radiographic signs of post-traumatic
      osteoarthritis (OA) 2-3 years after anterior cruciate ligament (ACL)
      reconstruction through multivariable analysis of minimum joint space width (mJSW)
      differences in a specially designed nested cohort. METHODS: A nested cohort
      within the Multicenter Orthopaedic Outcomes Network (MOON) cohort included 262
      patients (148 females, average age 20) injured in sport who underwent ACL
      reconstruction in a previously uninjured knee, were 35 or younger, and did not
      have ACL revision or contralateral knee surgery. mJSW on semi-flexed radiographs
      was measured in the medial compartment using a validated computerized method. A
      multivariable generalized linear model was constructed to assess mJSW difference
      between the ACL reconstructed and contralateral control knees while adjusting for
      potential confounding factors. RESULTS: Unexpectedly, we found the mean mJSW was
      0.35 mm wider in ACL reconstructed than in control knees (5.06 mm (95% CI 4.96
      5.15 mm) vs 4.71 mm (95% CI 4.62-4.80 mm), P < 0.001). However, ACL reconstructed
      knees with meniscectomy had narrower mJSW compared to contralateral normal knees
      by 0.64 mm (95% C.I. 0.38-0.90 mm) (P < 0.001). Age (P < 0.001) and meniscus
      repair (P = 0.001) were also significantly associated with mJSW difference.
      CONCLUSION: Semi-flexed radiographs can detect differences in mJSW between ACL
      reconstructed and contralateral normal knees 2-3 years following ACL
      reconstruction, and the unexpected wider mJSW in ACL reconstructed knees may
      represent the earliest manifestation of post-traumatic osteoarthritis and
      warrants further study.

PMID- 25559583
TI  - Improving protein order-disorder classification using charge-hydropathy plots.
AB  - BACKGROUND: The earliest whole protein order/disorder predictor (Uversky et al.,
      Proteins, 41: 415-427 (2000)), herein called the charge-hydropathy (C-H) plot,
      was originally developed using the Kyte-Doolittle (1982) hydropathy scale (Kyte &
      Doolittle., J. Mol. Biol, 157: 105-132(1982)). Here the goal is to determine
      whether the performance of the C-H plot in separating structured and disordered
      proteins can be improved by using an alternative hydropathy scale. RESULTS: Using
      the performance of the CH-plot as the metric, we compared 19 alternative
      hydropathy scales, with the finding that the Guy (1985) hydropathy scale (Guy,
      Biophys. J, 47:61-70(1985)) was the best of the tested hydropathy scales for
      separating large collections structured proteins and intrinsically disordered
      proteins (IDPs) on the C-H plot. Next, we developed a new scale, named IDP
      Hydropathy, which further improves the discrimination between structured proteins
      and IDPs. Applying the C-H plot to a dataset containing 109 IDPs and 563 non
      homologous fully structured proteins, the Kyte-Doolittle (1982) hydropathy scale,
      the Guy (1985) hydropathy scale, and the IDP-Hydropathy scale gave balanced two
      state classification accuracies of 79%, 84%, and 90%, respectively, indicating a
      very substantial overall improvement is obtained by using different hydropathy
      scales. A correlation study shows that IDP-Hydropathy is strongly correlated with
      other hydropathy scales, thus suggesting that IDP-Hydropathy probably has only
      minor contributions from amino acid properties other than hydropathy. CONCLUSION:
      We suggest that IDP-Hydropathy would likely be the best scale to use for any type
      of algorithm developed to predict protein disorder.

PMID- 25559584
TI  - Massively parallel single-amino-acid mutagenesis.
AB  - Random mutagenesis methods only partially cover the mutational space and are
      constrained by DNA synthesis length limitations. Here we demonstrate programmed
      allelic series (PALS), a single-volume, site-directed mutagenesis approach using
      microarray-programmed oligonucleotides. We created libraries including nearly
      every missense mutation as singleton events for the yeast transcription factor
      Gal4 (99.9% coverage) and human tumor suppressor p53 (93.5%). PALS-based
      comprehensive missense mutational scans may aid structure-function studies,
      protein engineering, and the interpretation of variants identified by clinical
      sequencing. 

PMID- 25559586
TI  - Enhanced performance of ZnO piezotronic pressure sensor through electron
      tunneling modulation of MgO nanolayer.
AB  - Piezoelectric materials can be applied into electromechanical conversion and
      attract extensive attention with potential applications in various sensors. Here,
      we present two types of piezotronic pressure sensors based on ZnO nanoarrays. By
      introducing an insulating MgO (i-MgO) nanolayer, the "on/off" current ratio of
      the sensor is significantly improved up to 10(5). Furthermore, the sensor shows a
      high sensitivity of 7.1 * 10(4) gf(-1), a fast response time of 128 ms. The
      excellent properties are attributed to the combination of piezoelectric effect of
      ZnO nanoarrays and electron-tunneling modulation of MgO nanolayer, and the
      reversible potential barrier height controlled by piezoelectric potential. We
      further investigate the service behavior of the sensor, which can detect force
      varying from 3.2 to 27.2 gf. Our research provides a promising approach to boost
      the performance of nanodevices. 

PMID- 25559585
TI  - Loss of non-coding RNA expression from the DLK1-DIO3 imprinted locus correlates
      with reduced neural differentiation potential in human embryonic stem cell lines.
AB  - INTRODUCTION: Pluripotent stem cells are increasingly used to build therapeutic
      models, including the transplantation of neural progenitors derived from human
      embryonic stem cells (hESCs). Recently, long non-coding RNAs (lncRNAs), including
      delta-like homolog 1 gene and the type III iodothyronine deiodinase gene (DLK1
      DIO3) imprinted locus-derived maternally expressed gene 3 (MEG3), were found to
      be expressed during neural development. The deregulation of these lncRNAs is
      associated with various neurological diseases. The imprinted locus DLK1-DIO3
      encodes abundant non-coding RNAs (ncRNAs) that are regulated by differential
      methylation of the locus. We aim to study the correlation between the DLK1-DIO3
      derived ncRNAs and the capacity of hESCs to differentiate into neural lineages.
      METHODS: We classified hESC sublines into MEG3-ON and MEG3-OFF based on the
      expression levels of MEG3 and its downstream microRNAs as detected by
      quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A cDNA
      microarray was used to analyze the gene expression profiles of hESCs. To
      investigate the capacity of neural differentiation in MEG3-ON and MEG3-OFF hESCs,
      we performed neural lineage differentiation followed by neural lineage marker
      expression and neurite formation analyses via qRT-PCR and immunocytochemistry,
      respectively. MEG3-knockdown via small interfering RNA (siRNA) and small hairpin
      RNA (shRNA) was used to investigate the potential causative effect of MEG3 in
      regulating neural lineage-related gene expression. RESULTS: DLK1-DIO3-derived
      ncRNAs were repressed in MEG3-OFF hESCs compared with those in the MEG3-ON hESCs.
      The transcriptome profile indicated that many genes related to nervous system
      development and neural-type tumors were differentially expressed in MEG3-OFF
      hESCs. Three independent MEG3-knockdown assays using different siRNA and shRNA
      constructs consistently resulted in downregulation of some neural lineage genes.
      Lower expression levels of stage-specific neural lineage markers and reduced
      neurite formation were observed in neural lineage-like cells derived from MEG3
      OFF-associated hESCs compared with those in the MEG3-ON groups at the same time
      points after differentiation. CONCLUSIONS: Repression of ncRNAs derived from the
      DLK1-DIO3 imprinted locus is associated with reduced neural lineage
      differentiation potential in hESCs.

PMID- 25559588
TI  - Splitting and joining in carbon nanotube/nanoribbon/nanotetrahedron growth.
AB  - We report a novel phenomenon for carbon nanotube growth that results in a new
      carbon nanotube morphology. A carbon nanotube grown via metal nanoparticle
      catalyzed chemical vapor deposition splits into two flattened nanotubes during
      growth and the two flattened nanotubes merge to form a ring of carbon
      nanotube/nanoribbon. This novel process is revealed by transmission electron
      microscopy observations of the carbon nanostructures. We propose that the
      splitting-and-joining process involves only one metal catalyst nanoparticle and a
      self-folding mechanism that we have named the origami mechanism to explain the
      process and the formation of nanoribbons and nanotetrahedra. 

PMID- 25559587
TI  - Disparities of Plasmodium falciparum infection, malaria-related morbidity and
      access to malaria prevention and treatment among school-aged children: a national
      cross-sectional survey in Cote d'Ivoire.
AB  - BACKGROUND: There is limited knowledge on the malaria burden of school-aged
      children in Cote d'Ivoire. The aim of this study was to assess Plasmodium
      falciparum infection, malaria-related morbidity, use of preventive measures and
      treatment against malaria, and physical access to health structures among school
      aged children across Cote d'Ivoire. METHODS: A national, cross-sectional study
      was designed, consisting of clinical and parasitological examinations and
      interviews with schoolchildren. More than 5,000 children from 93 schools in Cote
      d'Ivoire were interviewed to determine household socioeconomic status, self
      reported morbidity and means of malaria prevention and treatment. Finger-prick
      blood samples were collected and Plasmodium infection and parasitaemia determined
      using Giemsa-stained blood films and a rapid diagnostic test (RDT). Haemoglobin
      levels and body temperature were measured. Children were classified into wealth
      quintiles using household assets and principal components analysis (PCA). The
      concentration index was employed to determine significant trends of health
      variables according to wealth quintiles. Logistic and binomial negative
      regression analyses were done to investigate for associations between P.
      falciparum prevalence and parasitaemia and any health-related variable. RESULTS:
      The prevalence of P. falciparum was 73.9% according to combined microscopy and
      RDT results with a geometric mean of parasitaemia among infected children of 499
      parasites/MUl of blood. Infection with P. falciparum was significantly associated
      with sex, socioeconomic status and study setting, while parasitaemia was
      associated with age. The rate of bed net use was low compared to the rate of bed
      net ownership. Preventive measures (bed net ownership, insecticide spray and the
      reported use of malaria treatment) were more frequently mentioned by children
      from wealthier households who were at lower risk of P. falciparum infection. Self
      reported morbidity (headache) and clinical morbidity (anaemia) were more often
      reported by children from less wealthy households. CONCLUSION: Seven out of ten
      school-aged children in Cote d'Ivoire are infected with P. falciparum and malaria
      related morbidity is considerable. Furthermore, this study points out that bed
      net usage is quite low and there are important inequalities in preventive
      measures and treatment. These results can guide equity-oriented malaria control
      strategies in Cote d'Ivoire.

PMID- 25559589
TI  - Early postoperative single treatment ablative fractional lasing of Mohs
      micrographic surgery facial scars: a split-scar, evaluator-blinded study.
AB  - BACKGROUND/OBJECTIVES: Despite precise surgical technique, some postoperative
      facial scars will depress and widen over time, likely due to weakened or
      inadequately replaced collagen fibers in the underlying dermis. The purpose of
      this study is to evaluate whether a 10,600 nm ablative carbon dioxide (CO2 )
      fractional laser used early in the post-surgical setting results in improved
      postoperative facial scars after a single treatment session. STUDY DESIGN: A
      prospective randomized, comparative split-scar study was conducted on 20 subjects
      between the ages of 20-90. Subjects underwent Mohs surgery for nonmelanoma skin
      cancer of the face. Subsequent to tumor removal, subjects with a linear scar of 4
      cm or greater were enrolled. On the day of suture removal, all subjects had one
      half of their scar randomly selected and treated with a 10,600 nm CO2 fractional
      laser (energy = 10 mJ; density = 10%; spot size = 7 mm; pulse = 1). The untreated
      scar half served as a control. Scars were re-evaluated 12 weeks later. An
      independent blinded observer graded the scar halves with the Vancouver scar scale
      (VSS) immediately prior to treatment and 12 weeks after treatment. Subjects
      completed a visual analog scale (VAS) at the same time points. RESULTS: Three
      months after laser treatment, a significant decrease in VSS and 3 of the 4 of its
      individual parameters were detected in both control and treated halves of the
      scar. When comparing the laser group versus the control group, a statistically
      significant difference was not noted in VSS (P = 0.31) but a statistically
      significant difference in patient VAS was detected (P = 0.002). No side effects
      of the laser treatment were noted. CONCLUSION: Facial wounds sutured in a layered
      manner heal well. Patients prefer early fractional CO2 lasing of surgical scars,
      though use of the VSS failed to detect an objective difference between laser and
      control halves of scars. Conservative laser settings, a single session treatment,
      and VSS insensitivity for surgical scars may influence these findings.

PMID- 25559590
TI  - Effect of pregnancy and the postpartum period on adherence to antiretroviral
      therapy among HIV-infected women established on treatment.
AB  - : Among women who become pregnant after initiating highly active antiretroviral
      therapy (HAART), few data describe the effect of pregnancy and postpartum on
      adherence. We conducted a retrospective clinical cohort study among therapy-naive
      women (age, 18-45 years) initiating HAART in Johannesburg, South Africa. Among
      7510 women in our analysis, 896 experienced a pregnancy after starting HAART.
      Compared with nonpregnant periods of follow-up, there was an increased risk of
      nonadherence during the postpartum period (weighted risk ratio: 1.46, 95%
      confidence interval: 1.17 to 1.82) but not during pregnancy itself (weighted risk
      ratio: 0.95, 95% confidence interval: 0.78 to 1.17). 

PMID- 25559591
TI  - Female sexual partners of male people who inject drugs in vietnam have poor
      knowledge of their male partners' HIV status.
AB  - BACKGROUND: Vietnam's HIV epidemic is concentrated among male people who inject
      drugs (PWID), and their female sexual partners (SPs) may be at risk for
      infection. HIV prevention interventions for SPs were implemented in Hanoi, Dien
      Bien Province, and Ho Chi Minh City (HCMC), and data from linked surveys used to
      evaluate these interventions offered an unusual opportunity to assess knowledge
      of HIV status within couples. METHODS: Linked surveys (behavioral interviews and
      HIV testing) among 200 PWID-SP couples in Hanoi, 300 in Dien Bien, and 249 in
      HCMC. RESULTS: HIV prevalence among male PWID was 53% in Hanoi, 30% in Dien Bien,
      and 46% in HCMC, and lower among their SPs: 44%, 10%, and 37%, respectively.
      Comparison of SPs' beliefs regarding male PWID partners' HIV status with the
      PWIDs' actual test results revealed that 32% of SPs in Dien Bien and 44% in Hanoi
      and HCMC lacked correct knowledge of their male partners' status. This proportion
      was slightly lower (21%-33%) among SPs whose PWID partners reported having been
      previously tested and received HIV+ results. CONCLUSIONS: SP interventions
      reached HIV-negative women in serodiscordant relationships, and some improvements
      occurred in condom use and relationship characteristics. Nevertheless, our
      findings suggest that at least 11,000 SPs in Vietnam may be at high risk for HIV
      infection because of incorrect knowledge of their partners' HIV status.
      Interventions should be strengthened in HIV testing, disclosure, and treatment,
      as well as empowerment of SPs as individuals, within couples, and as communities.

PMID- 25559592
TI  - Baseline antiretroviral resistance mutations and treatment-emergent resistance in
      HIV-1 RNA-suppressed patients switching to EVG/COBI/FTC/TDF or continuing on
      their PI-, NNRTI-, or RAL-based regimen.
AB  - BACKGROUND: Stably suppressed HIV-1-infected patients that switched to
      elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate
      (EVG/COBI/FTC/TDF) from regimens containing FTC/TDF plus a ritonavir-boosted
      protease inhibitor (PI + RTV), nonnucleoside reverse transcriptase inhibitor
      (NNRTI), or raltegravir in phase 3 studies STRATEGY-PI, STRATEGY-NNRTI, and GS-US
      236-0123 maintained high rates of virologic suppression through 48 weeks. In this
      article, resistance analyses for these studies are described. METHODS: HIV-1
      historical genotypes obtained before therapy initiation were analyzed for
      preexisting/transmitted resistance (-R) in protease and reverse transcriptase
      (RT) and subtype. Patients with resistance to FTC/TDF were excluded. Viral
      isolates with HIV-1 RNA >=400 copies per milliliter at confirmed virologic
      failure, discontinuation, or week 48 were analyzed for protease, RT, and
      integrase genotype and phenotype. RESULTS: Historical genotypes from 626/628
      subjects that switched to EVG/COBI/FTC/TDF indicated 25% had >=1 primary
      resistance mutation in protease and/or RT. NNRTI-R was identified in 15%, NRTI-R
      in 8.3%, and PI-R in 3.7% of subjects. Week 48 virologic success rates (HIV-1 RNA
      <50 copies per milliliter) were 94% for all patients treated with
      EVG/COBI/FTC/TDF, 94% with preexisting resistance, 93% with subtype B, and 96%
      with non-B subtypes. Altogether, 2 subjects qualified for postbaseline resistance
      analyses. Neither had emergent resistance, and both resuppressed to HIV-1 RNA <50
      copies per milliliter with no change in therapy. CONCLUSIONS: Switching
      antiretroviral regimens to EVG/COBI/FTC/TDF in HIV-1 RNA-suppressed FTC/TDF
      sensitive patients resulted in maintained virologic suppression through 48 weeks.
      Similar virologic success rates were achieved irrespective of the presence of
      preexisting resistance mutations or subtype. The lack of emergent resistance
      through 48 weeks supports utility of EVG/COBI/FTC/TDF for treatment-experienced
      patients seeking regimen modification or simplification.

PMID- 25559593
TI  - High prevalence of transmitted drug resistance in acute HIV-infected Thai men who
      have sex with men.
AB  - : As use of antiretroviral therapy in Thailand increases, so does the potential
      for transmission of drug-resistant HIV. We describe the prevalence of WHO
      surveillance drug resistance mutations among 120 subjects who underwent genotypic
      testing during acute HIV infection in Bangkok, Thailand. In this cohort of
      predominantly men who have sex with men, we observed an overall transmitted drug
      resistance prevalence of 9.2%, including nucleoside/nucleotide analog reverse
      transcriptase inhibitor 5.0%, nonnucleoside analog reverse transcriptase
      inhibitor 3.4%, and protease inhibitor 3.4%. These prevalence estimates are
      higher than previous reports of transmitted drug resistance in Thailand. Baseline
      drug resistance testing may be warranted, particularly among men who have sex
      with men. 

PMID- 25559594
TI  - Accuracy of highly sexually active gay and bisexual men's predictions of their
      daily likelihood of anal sex and its relevance for intermittent event-driven HIV
      pre-exposure prophylaxis.
AB  - OBJECTIVE: We sought to examine highly sexually active gay and bisexual men's
      accuracy in predicting their sexual behavior for the purposes of informing future
      research on intermittent event-driven HIV Pre-Exposure Prophylaxis. DESIGN: For
      30 days, 92 HIV-negative men completed a daily survey about their sexual behavior
      (n = 1688 days of data) and indicated their likelihood of having anal sex with a
      casual male partner next day. METHOD: We used multilevel modeling to analyze the
      association between self-reported likelihood of and subsequent engagement in anal
      sex. RESULTS: We found a linear association between men's reported likelihood of
      anal sex with casual partners and the actual probability of engaging in sex,
      although men overestimated the likelihood of sex. Overall, we found that men were
      better at predicting when they would not have sex than when they would,
      particularly if any likelihood value greater than 0% was treated as indicative
      that sex might occur. We found no evidence that men's accuracy of prediction was
      affected by whether it was a weekend or whether they were using substances,
      although both did increase the probability of sex. DISCUSSION: These results
      suggested that, men taking event-driven intermittent Pre-Exposure Prophylaxis,
      14% of doses could have been safely skipped with a minimal rate of false
      negatives using guidelines of taking a dose unless there was no chance (ie, 0%
      likelihood) of sex on next day. This would result in savings of over US $1300 per
      year in medication costs per participant.

PMID- 25559597
TI  - HIV prevention through the lens of behavioral economics.

PMID- 25559596
TI  - No relationship between drug transporter genetic variants and tenofovir plasma
      concentrations or changes in glomerular filtration rate in HIV-infected adults.

PMID- 25559598
TI  - Young MSM at the leading edge of HIV in New York City: back to the future?

PMID- 25559595
TI  - Changes in HIV RNA and CD4 cell count after acute HCV infection in chronically
      HIV-infected individuals.
AB  - OBJECTIVE: Little is known about the impact of acute hepatitis C virus (HCV) co
      infection on HIV-1 disease progression. We investigated CD4 cell count and HIV
      RNA concentration changes after HCV infection in individuals chronically infected
      with HIV-1. METHODS: We selected individuals that had the last negative and first
      positive HCV RNA test less than 1 year apart. Bivariate linear mixed-effects
      regression was used to model trends in HIV RNA level and CD4 cell count from 2
      years before the last negative HCV RNA test until the first of the following
      dates: start of anti-HCV medication, change in combination antiretroviral therapy
      (cART) status, and end of follow-up. RESULTS: At the estimated time of HCV co
      infection, of 89 individuals, 63 (71%) were cART-treated and 26 (29%) were not on
      cART. In persons on cART, median CD4 cell count declined from 587 to 508 cells
      per cubic millimeter (P < 0.0001) during the first 5 months after HCV infection
      and returned to 587 cells per cubic millimeter after 2.2 years. Also, the
      probability of an HIV RNA >50 copies per milliliter peaked to 18.6% at HCV co
      infection, with lower probabilities 6 months before (3.5%, P = 0.006 compared
      with peak probability) and after (2.9%, P = 0.009). In persons not on cART, no
      significant impact of HCV co-infection on trends in the HIV RNA level or CD4 cell
      count was observed. CONCLUSIONS: Acute HCV infection in cART-treated, chronically
      HIV-infected patients was associated with a temporary decrease in CD4 cell counts
      and increased risk of HIV viremia >50 copies per milliliter. This may increase
      the risk of further HIV transmission.

PMID- 25559599
TI  - Virological efficacy of a reduced dose of nevirapine in a small cohort of
      suppressed HIV-1-infected patients.

PMID- 25559600
TI  - Outcomes from treating tuberculosis with rifampicin or rifabutin in HIV-infected
      persons also receiving antiretroviral therapy.

PMID- 25559601
TI  - Impact of hepatitis coinfection on healthcare utilization among persons living
      with HIV.
AB  - : Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection are
      increasingly important sources of morbidity among HIV-infected persons. We
      determined associations between hepatitis coinfection and healthcare utilization
      among HIV-infected adults at 4 US sites during 2006-2011. Outpatient HIV visits
      did not differ by hepatitis serostatus and decreased over time. Mental health
      visits were more common among HIV/HCV coinfected persons than among HIV
      monoinfected persons [incidence rate ratio (IRR): 1.27, 95% confidence interval
      (CI): 1.08 to 1.50]. Hospitalization rates were higher among all hepatitis
      infected groups than among HIV monoinfected (HIV/HBV: IRR: 1.23, 95% CI: 1.05 to
      1.44; HIV/HCV: IRR: 1.22, 95% CI: 1.10 to 1.36; HIV/HBV/HCV: IRR: 1.31, 95% CI:
      1.02 to 1.68). These findings may inform the design of clinical services and
      allocation of resources. 

PMID- 25559603
TI  - Single nucleotide polymorphisms of CXCL9-11 chemokines are associated with liver
      fibrosis in HIV/HCV-coinfected patients.
AB  - BACKGROUND: CXCR3A-associated chemokines (CXCL9-11) are implicated in the
      pathogenesis of hepatitis C virus (HCV) infection. We analyzed the association
      between CXCL9-11 polymorphisms and significant liver fibrosis in human
      immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We performed a
      cross-sectional study in 220 patients who were genotyped for CXCL9-11
      polymorphisms (CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915) using
      GoldenGate assay. Three outcome variables related to liver fibrosis were studied:
      (1) F >= 2; (2) APRI >= 2; and (3) FIB-4 >= 3.25. RESULTS: The percentage of
      patients with significant liver fibrosis (F >= 2, APRI >= 2, and FIB-4 >= 3.25)
      was significantly higher for CXCL9 rs10336 TT (P = 0.046, P = 0.010, and P =
      0.046, respectively), CXCL10 rs3921 GG (P = 0.046, P = 0.011, and P = 0.049,
      respectively), and CXCL11 rs4619915 AA (P = 0.035, P = 0.014, and P = 0.057,
      respectively) genotypes. Moreover, the greater likelihood of having significant
      liver fibrosis (F >= 2, APRI >= 2, and FIB-4 >= 3.25) was found in carriers of
      CXCL9 rs10336 TT and CXCL10 rs3921 GG [adjusted odds ratio (aOR) > 2 (P < 0.05)].
      These trends were significantly more pronounced in patients infected with HCV
      genotype 1 (GT1) [aOR > 3 (P < 0.05)]. Moreover, TGA haplotype showed higher odds
      for having values of APRI >= 2 (aOR = 2.4; P = 0.012) when we considered all
      patients. This elevated risk for significant liver fibrosis was better
      represented in patients infected with HCV-GT1, where TGA haplotype had increased
      odds for having values of F >= 2 (aOR = 1.9; P = 0.045), APRI >= 2 (aOR = 3.2; P
      = 0.009), and FIB-4 >= 3.25 (aOR = 3.3; P = 0.026). CONCLUSIONS: The homozygosity
      for the minor alleles CXCL9 rs10336 (T), CXCL10 rs3921 (G), and CXCL11 rs4619915
      (A) is associated with the higher likelihood of significant liver fibrosis in HIV
      infected patients coinfected with HCV-GT1.

PMID- 25559605
TI  - Clinic-wide intervention lowers financial risk and improves revenue to HIV
      clinics through fewer missed primary care visits.
AB  - : We calculated the financial impact in 6 HIV clinics of a low-effort retention
      in care intervention involving brief motivational messages from providers,
      patient brochures, and posters. We used a linear regression model to calculate
      absolute changes in kept primary care visits from the preintervention year (2008
      2009) to the intervention year (2009-2010). Revenue from patients' insurance was
      also assessed by clinic. Kept visits improved significantly in the intervention
      year versus the preintervention year (P < 0.0001). We found a net-positive effect
      on clinic revenue of +$24,000/year for an average-size clinic (7400 scheduled
      visits/year). We encourage HIV clinic administrators to consider implementing
      this low-effort intervention. 

PMID- 25559607
TI  - Benefits of policy support of a healthy eating initiative in schools.

PMID- 25559606
TI  - The effect of HIV viral control on the incidence of hepatocellular carcinoma in
      veterans with hepatitis C and HIV coinfection.
AB  - BACKGROUND: HIV increases the risk of progression to hepatic fibrosis and
      cirrhosis among individuals coinfected with hepatitis C virus (HCV). However, the
      impact of HIV-related immune suppression on the risk of hepatocellular carcinoma
      (HCC) is currently unknown. METHODS: We used the Veterans Affairs HIV Clinical
      Case Registry to identify patients with HIV infection between 1985 and 2010 and
      HCV coinfection (positive HCV RNA or genotype test) between 1995 and 2010. The
      outcome was incident HCC as indicated by International Classification of
      Diseases, 9th revision, Clinical Modification code (87% positive predictive
      value). Patients with HCV monoinfection were included as a comparison group for
      HCC incidence. Age-adjusted HCC incidence rates were calculated for the
      coinfected cohort and HCV monoinfected cohort. Cox proportional hazard models
      were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for
      each risk factor on the time to HCC diagnosis in the coinfected cohort. RESULTS:
      There were 66,991 veterans with HIV; 8563 had at least 1 positive HCV RNA test,
      and 234 of these developed HCC. The overall age-adjusted incidence rate of HCC in
      monoinfected patients was 2.99/1000 person-years vs. 4.44/1000 person-years in
      coinfected patients. In patients with coinfection, presence of cirrhosis (HR =
      4.88; 95% CI: 3.30 to 7.21), HIV diagnosis >2002 (HR = 4.65; 95% CI: 2.70 to
      8.02), and a recent low CD4 cell count <200 (HR = 1.71; 95% CI: 1.20 to 2.45)
      were associated with an increased risk for HCC. CONCLUSIONS: The risk of HCC in
      HCV- and HIV-coinfected veteran men was higher than HCV monoinfection. Diagnosis
      of cirrhosis and low recent CD4 cell count were the most important predictors of
      developing HCC in this group.

PMID- 25559604
TI  - Impact of age on retention in care and viral suppression.
AB  - BACKGROUND: Retention in care is important for all HIV-infected persons and is
      strongly associated with initiation of antiretroviral therapy and viral
      suppression. However, it is unclear how retention in care and age interact to
      affect viral suppression. We evaluated whether the association between retention
      and viral suppression differed by age at entry into care. METHODS: Cross
      sectional analysis (2006-2010) involving 17,044 HIV-infected adults in 14
      clinical cohorts across the United States and Canada. Patients contributed 1 year
      of data during their first full-calendar year of clinical observation. Poisson
      regression examined associations between retention measures [US National HIV/AIDS
      Strategy (NHAS), US Department of Health and Human Services (DHHS), 6-month gap,
      and 3-month visit constancy] and viral suppression (HIV RNA <=200 copies/mL) by
      age group: 18-29 years, 30-39 years, 40-49 years, 50-59 years, and 60 years or
      older. RESULTS: Overall, 89% of patients were retained in care using the NHAS
      measure, 74% with the DHHS indicator, 85% did not have a 6-month gap, and 62% had
      visits in 3-4 quarters of the year; 54% achieved viral suppression. For each
      retention measure, the association with viral suppression was significant for
      only the younger age groups (18-29 and 30-39 years): 18-29 years [adjusted
      prevalence ratio (APR) = 1.33, 95% confidence interval (CI): 1.03 to 1.70]; 30-39
      years (APR = 1.23, 95% CI: 1.01 to 1.49); 40-49 years (APR = 1.06, 95% CI: 0.90
      to 1.22); 50-59 (APR = 0.92, 95% CI: 0.75 to 1.13); >=60 years (APR = 0.99, 95%
      CI: 0.63 to 1.56) using the NHAS measure as a representative example.
      CONCLUSIONS: These results have important implications for improving viral
      control among younger adults, emphasizing the crucial role retention in care
      plays in supporting viral suppression in this population.

PMID- 25559608
TI  - Enhanced transport into and out of dead-end pores.
AB  - Dead-end micro- and nanoscale channels are ubiquitous in nature and are found in
      geological and biological systems subject to frequent disruptions. Achieving
      fluid flows in them is not possible through conventional pressure-driven
      mechanisms. Here we show that chemically driven convective flows leading to
      transport in and out of dead-end pores can occur by the phenomenon of "transient
      diffusioosmosis". The advective velocity depends on the presence of an in situ
      generated transient ion gradient and the intrinsic charge on the pore wall. The
      flows can reach speeds of 50 MUm/s and cause extraction of otherwise-trapped
      materials. Our results illustrate that chemical energy, in the form of a
      transient salt gradient, can be transduced into mechanical motion with the pore
      wall acting as the pump. As discussed, the phenomena may underlie observed
      transport in many geological and biological systems involving tight or dead-end
      micro- and nanochannels. 

PMID- 25559609
TI  - Simultaneous analysis of N(epsilon) -(carboxymethyl)Lysine and N(epsilon) 
      (carboxyethyl)lysine in foods by ultra-performance liquid chromatography-mass
      spectrometry with derivatization by 9-fluorenylmethyl chloroformate.
AB  - Isotope dilution ultra-performance liquid chromatography-electrospray tandem mass
      spectrometry with derivatization by 9-fluorenylmethyl chloroformate was
      successfully applied to quantify N(epsilon) -(carboxymethyl)lysine (CML) and
      N(epsilon) -(carboxyethyl)lysine (CEL) in processed foods. We demonstrate that
      this analytical method is well validated for the determination of CML and CEL
      contents in processed foods. Relative standard deviations (RSD) indicate
      repeatability (RSD < 6% for CML and CEL) and reproducibility (RSD < 6% for CML
      and < 7% for CEL) in this method. Percent recovery is also good. We obtain
      recoveries of 102% to 112% for CML and 86% to 114% for CEL. CML levels detected
      in the samples vary from 2.29 to 480 mg/kg food, whereas CEL is detected in
      significantly lower concentrations ranging from 0.56 to 107 mg/kg food. These
      data could help consumers make better food choices by monitoring intake of
      advanced glycation end-products, which may pose a risk to human health. 

PMID- 25559611
TI  - Extraction procedure optimization and the characteristics of dissolved
      extracellular organic matter (dEOM) and bound extracellular organic matter (bEOM)
      from Chlorella pyrenoidosa.
AB  - The influence of extracellular organic matter (EOM) on membrane fouling is
      important for algae cultivation and harvest. Therefore, a deep understanding of
      EOM and a systematic extraction process are necessary. In this study, EOM from
      Chlorella pyrenoidosa was thoroughly studied by using different methods to
      stratify it into dEOM and bEOM. Among these methods, the centrifugation method
      was optimized for dEOM extraction, and the heating and NaOH methods were
      optimized for bEOM extraction. In addition, dEOM and bEOM were compared by using
      analytical methods to obtain their protein and polysaccharide contents, dissolved
      organic carbon (DOC) contents, specific UV absorbances (SUVA), zeta potentials,
      FTIR spectra, EEM fluorescence spectra, hydrophobicities and molecular weights.
      The dEOM and bEOM both primarily consisted of proteins and polysaccharides and
      carried negative charges with relatively low SUVAs. The protein/polysaccharide
      ratios in the bEOM were 6.35 (control), 12.54 (heating) and 7.54 (NaOH) mg mg(
      1), which were greater than the ratio of the dEOM (2.93 mg mg(-1)). Furthermore,
      the hydrophobicity analysis indicated that the bEOM had higher hydrophobic
      fraction content than the dEOM. However, both types of EOM were more hydrophilic
      in terms of the DOC. Finally, size fraction analysis indicated that high-MW (>100
      kDa) and low-MW fractions (<1 kDa) were the primary components in EOMs.
      Specifically, a greater high-MW fraction was observed in the bEOM, which
      primarily consisted of DOC and proteins. In contrast with the proteins, the
      polysaccharides of the dEOM and bEOM were primarily distributed in the
      hydrophilic and low-MW fractions. Using comparative analysis, centrifugation at
      10,000*g for 10 min was chosen as the best method for extracting dEOM. In
      contrast, heating at 70 degrees C for 20 min was the best method for extracting
      bEOM.

PMID- 25559610
TI  - The N-terminal propeptide of type III procollagen in patients with acute coronary
      syndrome: a link between left ventricular end-diastolic pressure and
      cardiovascular events.
AB  - BACKGROUND: Despite the usefulness of N-terminal propeptide of type III
      procollagen (PIIINP) in detecting enhanced collagen turnover in patients with
      congestive heart failure, the value added by PIIINP to the use of clinical
      variables and echocardiography in relation to directly measured left ventricular
      (LV) end-diastolic pressure (EDP) and the outcome of acute coronary syndrome
      (ACS) has not been clearly defined. METHODS AND RESULTS: This study involved 168
      adult patients with ACS, who underwent echocardiography, measurement of serum
      PIIINP levels, and cardiac catheterization. Pulsed wave tissue Doppler imaging
      (PWTDI), which revealed mean peak systolic (s'), early (e'), and late diastolic
      (a') velocities, was carried out and the eas index of LV function was evaluated:
      e'/(a'*s'). The patients were divided into three study groups based on the degree
      of LVEDP--normal (<16 mmHg), intermediate (16-30 mmHg), and high (>30 mmHg)
      LVEDP. All patients were followed-up to determine cardiac-related death and
      revascularization. Patients with high LVEDP had significantly more PIIINP than
      those with intermediate or normal LVEDP (all post hoc p<0.05). The presence of
      coronary artery disease, the left atrial volume index (LAVI), the ratio of
      transmitral early and late diastolic flow velocities, a', and the eas index were
      significantly correlated with LVEDP. According to multiple stepwise analysis,
      PIIINP, LAVI and the eas index were the three independent predictors of the level
      of LVEDP (PIIINP, p <0.001; LAVI, p = 0.007; eas index, p = 0.021). During follow
      up (median, 24 months), 32 participants suffered from cardiac events, PIIINP and
      LAVI were significant predictors of cardiac mortality and hospitalization
      (PIIINP, hazard ratio (HR) 2.589, p = 0.002; LAVI, HR 1.040, p = 0.027).
      CONCLUSIONS: PIIINP is a highly effective means to evaluate LVEDP in patients
      with ACS. The PIIINP is also correlated with cardiac mortality and
      revascularization, providing an additional means of evaluating and managing
      patients with ACS.

PMID- 25559613
TI  - Systemic thrombolysis for acute pulmonary embolism.
AB  - Acute pulmonary embolism is a frequent cause of hospitalization and is associated
      with a wide range of symptom severity. Anticoagulants are the mainstay of
      treatment for acute pulmonary embolism; however, in patients with massive or
      submassive pulmonary embolism, advanced therapy with thrombolytics may be
      considered. The decision to use thrombolytic therapy for acute pulmonary embolism
      should be based on careful risk-benefit analysis for each patient, including risk
      of morbidity and mortality associated with the embolism and risk of bleeding
      associated with the thrombolytic. Alteplase is currently the thrombolytic agent
      most studied and with the most clinical experience for this indication, although
      the most appropriate dose remains controversial, especially in patients with low
      body weight. When considering thrombolysis, unfractionated heparin is the
      preferred initial anticoagulant due to its short duration of action and its
      reversibility should bleeding occur.

PMID- 25559612
TI  - Impact of blood pressure on retinal microvasculature architecture across the
      lifespan: the Young Finns Study.
AB  - OBJECTIVE: The present study examined the impact of BP from childhood to mid
      adulthood on retinal microvascular architecture. METHODS: The Cardiovascular Risk
      in Young Finns Study included children aged 3-18 years, from five Finnish
      University cities, with participants chosen randomly from the national population
      registrar from those areas. The age of participants included in the current
      analyses in childhood (1980) ranged from three to nine years and in mid-adulthood
      (2011) ranged from 34 to 40 years (complete data n = 657). Measures of retinal
      microvasculature architecture measured in adulthood included diameters,
      tortuosity, lengths, and LDR. RESULTS: Regression analysis showed a strong
      negative association between childhood systolic BP and adult arteriolar diameter
      (standardized regression coefficient [beta] -0.300; p < 0.001) and with change in
      systolic BP from childhood to adulthood (beta = -0.249; p < 0.001). For
      arteriolar tortuosity, there was a strong positive association between childhood
      systolic BP and adult arteriolar tortuosity (beta = 0.154; p < 0.001) and no
      association with change in systolic BP from childhood to adulthood (beta = 0.072;
      p = 0.110). CONCLUSIONS: High BP in childhood and increased BP from childhood to
      adulthood impacts on retinal microvascular architecture in mid-adulthood.

PMID- 25559614
TI  - Developing discriminate model and comparative analysis of differentially
      expressed genes and pathways for bloodstream samples of diabetes mellitus type 2.
AB  - BACKGROUND: Diabetes mellitus of type 2 (T2D), also known as noninsulin-dependent
      diabetes mellitus (NIDDM) or adult-onset diabetes, is a common disease. It is
      estimated that more than 300 million people worldwide suffer from T2D. In this
      study, we investigated the T2D, pre-diabetic and healthy human (no diabetes)
      bloodstream samples using genomic, genealogical, and phonemic information. We
      identified differentially expressed genes and pathways. The study has provided
      deeper insights into the development of T2D, and provided useful information for
      further effective prevention and treatment of the disease. RESULTS: A total of
      142 bloodstream samples were collected, including 47 healthy humans, 22 pre
      diabetic and 73 T2D patients. Whole genome scale gene expression profiles were
      obtained using the Agilent Oligo chips that contain over 20,000 human genes. We
      identified 79 significantly differentially expressed genes that have fold change
      >= 2. We mapped those genes and pinpointed locations of those genes on human
      chromosomes. Amongst them, 3 genes were not mapped well on the human genome, but
      the rest of 76 differentially expressed genes were well mapped on the human
      genome. We found that most abundant differentially expressed genes are on
      chromosome one, which contains 9 of those genes, followed by chromosome two that
      contains 7 of the 76 differentially expressed genes. We performed gene ontology
      (GO) functional analysis of those 79 differentially expressed genes and found
      that genes involve in the regulation of cell proliferation were among most common
      pathways related to T2D. The expression of the 79 genes was combined with
      clinical information that includes age, sex, and race to construct an optimal
      discriminant model. The overall performance of the model reached 95.1% accuracy,
      with 91.5% accuracy on identifying healthy humans, 100% accuracy on pre-diabetic
      patients and 95.9% accuract on T2D patients. The higher performance on
      identifying pre-diabetic patients was resulted from more significant changes of
      gene expressions among this particular group of humans, which implicated that
      patients were having profound genetic changes towards disease development.
      CONCLUSION: Differentially expressed genes were distributed across chromosomes,
      and are more abundant on chromosomes 1 and 2 than the rest of the human genome.
      We found that regulation of cell proliferation actually plays an important role
      in the T2D disease development. The predictive model developed in this study has
      utilized the 79 significant genes in combination with age, sex, and racial
      information to distinguish pre-diabetic, T2D, and healthy humans. The study not
      only has provided deeper understanding of the disease molecular mechanisms but
      also useful information for pathway analysis and effective drug target
      identification.

PMID- 25559615
TI  - Systemic treatment of advanced hepatocellular carcinoma: from disillusions to new
      horizons.
AB  - Hepatocellular carcinoma (HCC) is an aggressive malignancy, which accounts for a
      third of all cancer deaths globally each year. The management of patients with
      HCC is complex, as both the tumour stage and any underlying liver disease must be
      considered conjointly. Since the approval of sorafenib in advanced HCC, several
      phase III clinical trials have failed to demonstrate any superiority over
      sorafenib in the frontline setting, and no agent has been shown to impact
      outcomes after sorafenib failure. This review will focus on the range of
      experimental therapeutics for patients with advanced HCC and highlight the
      successes and failures of these treatments as well as areas for future
      development. Specifics such as dose limiting toxicity and safety profile in
      patients with liver dysfunction related to the underlying chronic liver disease
      should be considered when developing therapies in HCC. Finally, robust validated
      and reproducible surrogate end-points as well as predictive biomarkers should be
      defined in future randomised trials. 

PMID- 25559616
TI  - Administration of standard-dose BEP regimen (bleomycin+etoposide+cisplatin) is
      essential for treatment of ovarian yolk sac tumour.
AB  - AIM: The aim of this study was to investigate prognostic factors, including
      postoperative chemotherapy regimen, for the treatment of ovarian yolk sac tumour
      (YST), and resulting fertility outcome. METHODS: A multi-institutional
      retrospective investigation was undertaken to identify patients with ovarian pure
      or mixed YST who were treated between 1980 and 2007. Postoperative chemotherapy
      regimen and other variables were assessed in univariate and multivariate
      analyses. Additionally, the reproductive safety of the BEP (bleomycin, etoposide
      and cisplatin) regimen was evaluated. RESULTS: There were 211 patients enrolled
      from 43 institutions. The BEP regimen and a non-BEP regimen were administered to
      112 and 99 patients as postoperative chemotherapy, respectively. In univariate
      and multivariate analyses, age?22, alpha-fetoprotein?33,000 ng/ml, residual
      tumours after surgery and non-BEP regimen were independently and significantly
      associated with poor overall survival (OS). BEP was significantly superior to non
      BEP in 5-year OS (93.6% versus 74.6%, P=0.0004). Reduced-dose BEP (<75% standard
      dose bleomycin and<50% etoposide dose) was significantly associated with poorer 5
      year OS compared with standard-dose BEP (89.4% versus 100%, P=0.02 and 62.5%
      versus 96.9%, P=0.0002). All patients who underwent fertility-sparing surgery
      recovered their menstrual cycles. Sixteen of 23 patients receiving BEP (70.0%)
      and 13 of 17 patients receiving non-BEP (76.5%) who were nulliparous at fertility
      sparing surgery and married at the time of investigation gave birth to 21 and 19
      healthy children, respectively. CONCLUSIONS: The results of the present study
      suggest that standard-dose BEP should be administered for ovarian YST. BEP is as
      safe as non-BEP for preserving reproductive function.

PMID- 25559617
TI  - Survival of older patients with metastasised breast cancer lags behind despite
      evolving treatment strategies--a population-based study.
AB  - BACKGROUND: Older women are more likely to be diagnosed with primary metastasised
      breast cancer than their younger counterparts. Evolving treatment strategies of
      metastasised breast cancer have resulted in improved survival in younger
      patients, but it remains unclear if this improvement has occurred in older
      patients as well. The aim of this study was to assess changes in treatment
      strategies over time in relation to overall and relative survival of older
      patients compared to younger patients with primary metastasised breast cancer.
      METHODS: All patients with a breast cancer diagnosis and distant metastases at
      first presentation (stage IV), between 1990 and 2012, were selected from the
      Netherlands Cancer Registry. Changes in treatment over time per age-group (<65
      years, 65-75 years and >75 years) were assessed using logistic regression.
      Overall survival over time was calculated using Cox Regression Models and
      relative survival was assessed using the Ederer II method. RESULTS: Overall,
      14,310 patients were included. Treatment strategies have strongly changed in the
      past twenty years; especially the use of chemotherapy has increased (P<0.001 in
      all age-groups). Overall survival of patients <65 has significantly improved
      (Hazard Ratio (HR) per year 0.98, 95% Confidence Interval (CI) 0.98-0.99,
      P<0.001), but the survival of older patients has not improved (HR 1.00, 95% CI
      0.99-1.01, P=0.86 for patients aged 65-75 and HR 1.00, 95% CI 1.00-1.01, P=0.46
      for patients aged >75). Similarly, relative survival has improved in patients <65
      but not in women aged 65-75 and >75. CONCLUSION: Overall and relative survival of
      older patients with metastasised breast cancer at first presentation have not
      improved in recent years in contrast with the survival of younger patients,
      despite increased treatment with chemotherapy for women of all ages. Future
      studies should focus on stratification models that can be used to predict which
      patients may benefit from specific treatment options.

PMID- 25559618
TI  - Haploidentical stem cell transplantation augmented by CD45RA negative lymphocytes
      provides rapid engraftment and excellent tolerability.
AB  - BACKGROUND: Haploidentical donors are being increasingly used for allogeneic
      hematopoietic cell transplantation (HCT). However, the requisite T-cell depletion
      results in a profound and often long-lasting immunocompromised state, and donor
      lymphocyte infusions bring a risk of graft-versus-host disease (GVHD). Naive T
      cells are believed to be among the most alloreactive T-cell subset and can be
      identified by CD45RA expression. Allogeneic HCT using CD45RA depletion has not
      been previously described for haploidentical donors. PROCEDURE: Eight children
      with relapsed or refractory solid tumors were transplanted following
      myeloablative conditioning. Each patient received two cell products, one created
      by CD3 depletion and the other through CD45RA depletion. RESULTS: Median CD34
      recovery was 59.2% with CD45RA depletion, compared to 82.4% using CD3 depletion.
      Median CD3+ T-cell dose after CD45RA reduction was 99.2 * 10(6)  cells/kg, yet
      depletion of CD3+ CD45RA+ cells exceeded 4.5 log. CD45RA depletion also resulted
      in substantial depletion of B-cells (median 2.45 log). All eight patients
      engrafted within 14 days and rapidly achieved 100% donor chimerism. No acute GVHD
      or secondary graft failure was observed. CONCLUSIONS: CD45RA depletion is a novel
      approach to haploidentical HCT that offers rapid engraftment with minimal risk of
      GVHD.

PMID- 25559619
TI  - Effort discounting and its association with negative symptoms in schizophrenia.
AB  - INTRODUCTION: Deficits in the initiation and persistence of goal-directed
      behaviour are key aspects of schizophrenia. In this study, the association
      between these motivational deficits and discounting of reward value in function
      of increasing physical effort costs was investigated. METHODS: Effort-based
      decision-making was investigated in 40 patients with a DSM-IV diagnosis of
      schizophrenia and 30 age- and sex-matched healthy control subjects by means of an
      effort discounting task. To assess negative symptom severity, we made use of the
      Scale for the Assessment of Negative Symptoms as well as objective measurements
      of hedonic response to stimuli and motor activity levels. RESULTS: Patients as
      well as control subjects discounted the subjective value of rewards significantly
      with increasing physical effort costs. However, we failed to find a difference in
      the discounting curves between patients and controls. Furthermore, effort
      discounting was not associated with any of the negative symptoms measures.
      CONCLUSIONS: Physical effort discounting was not found to be associated with
      motivational symptoms in schizophrenia if other decision costs are constant.
      However, recent findings show that more cognitive effort and/or an interaction
      between effort and other decision costs (e.g. temporal delay or uncertainty) are
      associated with negative symptoms in schizophrenia. This should be investigated
      further in future research.

PMID- 25559621
TI  - Is DUBA putting the brake on Th17 cells?

PMID- 25559620
TI  - T cells recognizing a 11mer influenza peptide complexed to H-2D(b) show
      promiscuity for peptide length.
AB  - T-cell repertoire is selected according to self peptide-MHC (major
      histocompatibility complex) complexes in the thymus. Although most peripheral T
      cells recognize specific pathogen-derived peptides complexed to self-MHC
      exclusively, some possess cross-reactivity to other self or foreign peptides
      presented by self-MHC molecules; a phenomenon often termed T-cell receptor (TCR)
      promiscuity or degeneracy. TCR promiscuity has been attributed to various
      autoimmune conditions. On the other hand, it is considered a mechanism for a
      relatively limited TCR repertoire to deal with a potentially much larger
      antigenic peptide repertoire. Such property has also been utilized to bypass self
      tolerance for cancer vaccine development. Although many studies explored such
      degeneracy for peptide of the same length, few studies reported such properties
      for peptides of different length. In this study, we finely characterized the
      CD8(+) T-cell response specific for a 11mer peptide derived from influenza A
      viral polymerase basic protein 2. The short-term T-cell line, despite possessing
      highly biased TCR, was able to react with multiple peptides of different length
      sharing the same core sequence. Out data clearly showed the importance of
      detailed and quantitative assessments for such T-cell specificity. Our data also
      emphasize the importance of biochemical demonstration of the naturally presented
      minimal peptide. 

PMID- 25559624
TI  - Ibrutinib-associated lymphocytosis corresponds to bone marrow involvement in
      mantle cell lymphoma.

PMID- 25559623
TI  - Survival and biodistribution of xenogenic adipose mesenchymal stem cells is not
      affected by the degree of inflammation in arthritis.
AB  - BACKGROUND: Application of mesenchymal stem/stromal cells (MSCs) in treating
      different disorders, in particular osteo-articular diseases, is currently under
      investigation. We have already documented the safety of administrating human
      adipose tissue-derived stromal MSCs (hASCs) in immunodeficient mice. In the
      present study, we investigated whether the persistence of MSC is affected by the
      degree of inflammation and related to the therapeutic effect in two inflammatory
      models of arthritis. METHODOLOGY/PRINCIPAL FINDINGS: We used C57BL/6 or DBA/1
      mice to develop collagenase-induced osteoarthritis (CIOA) or collagen-induced
      arthritis (CIA), respectively. Normal and diseased mice were administered
      2.5*10(5) hASCs in the knee joints (i.a.) or 10(6) in the tail vein (i.v.). For
      CIA, clinical scores were monitored during the time course of the disease while
      for CIOA, OA scores were assessed by histology at euthanasia. Thirteen tissues
      were recovered at different time points and processed for real-time PCR and Alu
      sequence detection. Immunological analyses were performed at euthanasia. After
      i.v. infusion, no significant difference in the percentage of hASCs was
      quantified in the lungs of normal and CIA mice at day 1 while no cell was
      detected at day 10 taking into account the sensitivity of the assay, indicating
      that a high level of inflammation did not affect the persistence of cells. In
      CIOA mice, we reported the therapeutic efficacy of hASCs at reducing OA clinical
      scores at day 42 when hASCs were not detected in the joints. However, the
      percentage and distribution of hASCs were similar in osteoarthritic and normal
      mice at day 1 and 10 after implantation indicating that moderate inflammation
      does not alter hASC persistence in vivo. CONCLUSIONS/SIGNIFICANCE: While
      inflammatory signals are required for the immunosuppressive function of MSCs,
      they do not enhance their capacity to survive in vivo, as evaluated in two
      xenogeneic inflammatory pre-clinical models of arthritis.

PMID- 25559622
TI  - Beyond receptors and signaling: epigenetic factors in the regulation of innate
      immunity.
AB  - The interaction of innate immune cells with pathogens leads to changes in gene
      expression that elicit our body's first line of defense against infection.
      Although signaling pathways and transcription factors have a central role, it is
      becoming increasingly clear that epigenetic factors, in the form of DNA or
      histone modifications, as well as noncoding RNAs, are critical for generating the
      necessary cell lineage as well as context-specific gene expression in diverse
      innate immune cell types. Much of the epigenetic landscape is set during cellular
      differentiation; however, pathogens and other environmental triggers also induce
      changes in histone modifications that can either promote tolerance or 'train'
      innate immune cells for a more robust antigen-independent secondary response.
      Here we review the important contribution of epigenetic factors to the
      initiation, maintenance and training of innate immune responses. In addition, we
      explore how pathogens have hijacked these mechanisms for their benefit and the
      potential of small molecules targeting chromatin machinery as a way to boost or
      subdue the innate immune response in disease.

PMID- 25559625
TI  - Pocket analysis of the full-length cholix toxin. An assessment of the structure
      dynamics of the apo catalytic domain.
AB  - Cholix toxin from Vibrio cholerae is the third member of the diphtheria toxin
      (DT) group of mono-ADP-ribosyltransferase (mART) bacterial toxins. It shares
      structural and functional properties with Pseudomonas aeruginosa exotoxin A and
      Corynebacterium diphtheriae DT. Cholix toxin is an important model for the
      development of antivirulence approaches and therapeutics against these toxins
      from pathogenic bacteria. Herein, we have used the high-resolution X-ray
      structure of full-length cholix complexed with NAD(+) to describe the properties
      of the NAD(+)-binding pocket at the residue level, including the role of
      crystallographic water molecules in the NAD(+) substrate interaction. The full
      length apo cholix structure is used to describe the putative NAD(+)-binding
      site(s) and to correlate biochemical with crystallographic data to study the
      stoichiometry and orientation of bound NAD(+) molecules. We quantitatively
      describe the NAD(+) substrate interactions on a residue basis for the main 22
      pocket residues in cholixf, a glycerol and 5 contact water molecules as part of
      the recognition surface by the substrate according to the conditions of
      crystallization. In addition, the dynamic properties of an in silico version of
      the catalytic domain were investigated in order to understand the lack of
      electronic density for one of the main flexible loops (R-loop) in the pocket of X
      ray complexes. Implications for a rational drug design approach for mART toxins
      are derived. 

PMID- 25559627
TI  - Editor's Letter.

PMID- 25559626
TI  - Safety and benefits of self-expandable metallic stents with chemotherapy for
      malignant gastric outlet obstruction.
AB  - BACKGROUND AND AIM: The influence of chemotherapy on placement of self-expandable
      metallic stents (SEMS) for malignant gastric outlet obstruction (MGOO) has not
      been evaluated extensively. We investigated the influence of chemotherapy on the
      clinical outcomes of SEMS placement for MGOO. METHODS: A total of 152 cancer
      patients with MGOO from a university hospital and affiliate hospitals were
      included. The patients were classified according to chemotherapy status and
      evaluated for palliative efficacy and safety of SEMS placement. RESULTS:
      Technical success rate, time to oral intake, and parameters indicating
      improvement of physical condition did not differ between the with- and without
      chemotherapy groups after stent placement. Re-intervention and stent migration
      were significantly more frequent in the with-chemotherapy group than in the
      without-chemotherapy group after stent placement (re-intervention, 32.4% vs 7.8%,
      P = 0.0005; stent migration, 13.5% vs 1.7%, P = 0.0097). The frequency of adverse
      events did not differ between the with- and without-chemotherapy groups. Although
      chemotherapy after stent placement was an independent predictive factor for
      shortening the stent patency period (hazard ratio [HR], 3.10; P = 0.0264), the
      use of additional stents facilitated uneventful recovery and further prolonged
      survival time (HR, 0.60; P = 0.0132). CONCLUSIONS: Various cancer patients with
      MGOO can undergo SEMS placement safely regardless of chemotherapy, and concurrent
      chemotherapy after stent placement can prolong survival time, although re
      intervention and stent migration may be increased.

PMID- 25559628
TI  - Validation of a Brief Measure of Opioid Dependence: The Rapid Opioid Dependence
      Screen (RODS).
AB  - The Rapid Opioid Dependence Screen (RODS) is an 8-item measure of opioid
      dependence designed for quick, targeted screening in clinical and research
      settings. Based on the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth edition, criteria, the RODS has an average administration of less than 2
      minutes and can easily be administered as a stand-alone instrument or as part of
      a comprehensive interview. This study reports on the initial validation of the
      RODS among a sample of 97 newly incarcerated, HIV-positive individuals. Using the
      Mini International Neuropsychiatric Interview as the primary measure of opioid
      dependence, the RODS showed good-to-strong sensitivity (.97), specificity (.76),
      positive predictive value (.69), and negative predictive value (.98), while
      concordance analysis revealed moderate diagnostic agreement (kappa = .67).
      Psychometric properties revealed strong internal consistency (alpha = .92) and
      inter-item correlations (.66 to .87). 

PMID- 25559629
TI  - Weight patterns of youth entering an urban juvenile justice facility.
AB  - Adolescents with a history of incarceration face a disproportionate number of
      health issues compared with their peers in virtually all areas, including
      perceived well-being; self-esteem; acute, chronic, and psychosocial disorders;
      and physical activity. Some studies have shown correlates of weight status and
      incarceration; however, the literature is conflicting. The current study sought
      to assess weight patterns of primarily minority urban youth (N = 548) entering a
      juvenile justice facility as well as associations between medications and weight
      status. Results indicate incarcerated adolescents have higher rates of overweight
      and obesity (40%) in comparison with nonincarcerated adolescents in the state (20
      to 30%) or surrounding community (30 to 34%). Of interest, incarcerated
      adolescents taking asthma medications have significantly higher rates of
      overweight and obesity when compared with those not taking asthma medications.
      The clinical implications of these findings are discussed and implications for
      future research explored. 

PMID- 25559630
TI  - Patterns of traumatic injury in New York City prisoners requiring hospital
      admission.
AB  - Bellevue Hospital's prison ward cares for male prisoners requiring medical
      attention that exceeds the capabilities of New York City Department of Correction
      (NYC-DOC) infirmaries. This study evaluated the injury patterns that occur in
      this patient population. Data were collected on consecutive prisoners transferred
      from NYC-DOC for traumatic injuries from June 1, 2003, to June 1, 2006, and
      analyzed by retrospective chart review. Overall, 251 patients were evaluated for
      traumatic injuries. Injury mechanisms were violent (75.7%), nonviolent (23.5%),
      and self-inflicted (0.8%). Of the 241 (96%) patients admitted, 213 (84.9%)
      required operative intervention. The most common injuries were mandible fractures
      (46.5%) and facial fractures (14.9%). 

PMID- 25559631
TI  - Self-perceived health improvements among prison inmates.
AB  - Despite the extensive resources expended on providing medical care to inmates,
      inmates' health perception is an understudied topic. The current study
      investigates inmates' perception of health status while incarcerated using a
      sample of 136 soon-to-be released prisoners. Prisoners with poor health
      perception prior to their current incarceration were most likely to perceive
      health improvement. Sociodemographic characteristics were generally not
      associated with the perceived health improvement during incarceration. Analysis
      results suggest correctional institutions may play a vital role in delivering
      much-needed medical care to a segment of the prisoner population, including
      determining how they feel about their health. It is important to explore the
      policies and practices to increase continuity of health care following release to
      maintain perceived health improvement. 

PMID- 25559632
TI  - Academic-correctional health partnerships: preparing the correctional health
      workforce for the changing landscape-focus group research results.
AB  - Providing health care in corrections is challenging. Attracting clinicians can be
      equally challenging. The future holds a shortage of nurses and primary care
      physicians. We have a unique opportunity, now, to develop and stabilize our
      workforce, create a positive image, and enhance quality before the health care
      landscape changes even more dramatically. Focus groups were conducted with 22
      correctional health care professionals divided into three groups: physicians (6),
      nurses (4), and nurse practitioners/physician assistants (12). Content focused on
      curricular themes, but additional themes emerged related to recruitment and
      retention. This article describes recruitment challenges, strategic themes
      identified, and the proposed initiatives to support a stable, high-quality
      correctional health workforce. 

PMID- 25559633
TI  - Influenza in jails in developing countries.

PMID- 25559636
TI  - Age-related changes in hematologic and serum biochemical variables in dogs aged
      16-60 days.
AB  - BACKGROUND: The literature reporting hematologic and serum biochemical variables
      in puppies is limited. As puppies are physiologically different from adult dogs,
      an age effect would be expected. OBJECTIVES: We aimed to describe age-related
      changes in hematologic and serum biochemical variables in puppies aged 16-60 days
      and compare the results to reference intervals (RI) for adults. Our second aim
      was to determine RI for this age group. METHODS: A total of 227 blood samples
      were collected from 101 clinically healthy puppies, mainly mixed breeds. To
      assess the effect of age, the results were compared to RI for adult dogs, and
      variations within the age period 16-60 days were studied. Reference intervals for
      the groups 16-24, 28-45, and 46-60 days of age were determined. RESULTS: Lower
      values in puppies compared to adults were found for RBC, HGB, HCT, concentration
      of albumin, globulin, total protein, creatinine, and sodium:potassium ratio.
      Higher values in puppies compared to adults were found for activities of ALP and
      CK, and concentrations of inorganic phosphorus, calcium, and potassium. For MCV,
      MCHC, albumin:globulin ratio, and glucose concentration, different values in
      puppies compared to adults were found for some of the age groups. No age-specific
      differences were found compared to RI for adults regarding WBC, absolute counts
      of lymphocytes, neutrophils, monocytes, eosinophils, and platelets, RDW,
      activities for AST, ALT, amylase, lipase, and concentrations of bile acids,
      cholesterol, urea, sodium, and chloride. CONCLUSIONS: Our results support that
      age has a significant effect on several hematologic and serum biochemical values
      in puppies, warranting age-specific RI.

PMID- 25559637
TI  - Acute Effects of Stretching on Passive Properties of Human Gastrocnemius Muscle
      Tendon Unit: Analysis of Differences Between Hold-Relax and Static Stretching.
AB  - CONTEXT: Hold-relax stretching (HRS) and static stretching (SS) are commonly used
      to increase joint range of motion (ROM) and decrease muscle stiffness. However,
      whether there are differences between acute effects of HRS and SS on end ROM,
      passive torque, and muscle stiffness is unclear. In addition, any differences
      between the mechanisms by which HRS and SS lead to an increase in end ROM are
      unclear. OBJECTIVE: To compare the acute effects of HRS and SS on the passive
      properties of the gastrocnemius muscle-tendon unit (MTU), end ROM, passive
      torque, and muscle stiffness in vivo and to investigate the factors involved in
      increasing end ROM. DESIGN: Crossover experimental design. PARTICIPANTS: 30
      healthy men (21.7 +/- 1.2 y) with no history of neuromuscular disease or
      musculoskeletal injury involving the lower limbs. INTERVENTION: Both HRS and SS
      of 30 s were repeated 4 times, lasting a total of 2 min. MAIN OUTCOME MEASURES:
      End ROM, passive torque, and muscle stiffness were measured during passive ankle
      dorsiflexion using a dynamometer and ultrasonography before and immediately after
      HRS and SS. RESULTS: The results showed that end ROM and passive torque at end
      ROM significantly increased immediately after both HRS and SS, whereas muscle
      stiffness significantly decreased. In addition, the percentage change in passive
      torque at end ROM on use of the HRS technique was significantly higher than that
      after use of the SS technique. However, the percentage change in muscle stiffness
      after SS was significantly higher than that with HRS. CONCLUSION: These results
      suggest that both HRS and SS can effectively decrease muscle stiffness of the
      gastrocnemius MTU and that HRS induces a change in the passive torque at end ROM-
      i.e., sensory perception--rather than changing muscle stiffness.

PMID- 25559639
TI  - Pattern of linkage and retention in HIV care continuum among patients attending
      referral HIV care clinic in private sector in India.
AB  - Continued engagement throughout the HIV care continuum, from HIV diagnosis
      through retention on antiretroviral therapy (ART), is crucial for enhancing
      impact of HIV care programs. We assessed linkage and retention in HIV care among
      people living with HIV (PLHIV) enrolled at a private HIV care clinic in Pune,
      India. Of 1220 patients, 28% delayed linkage after HIV diagnosis with a median
      delay of 24 months (IQR = 8-43). Younger people, women, low socioeconomic status,
      and those diagnosed at facilities other than the study clinic were more likely to
      delay linkage. Those with advanced HIV disease at diagnosis and testing for HIV
      due to HIV-related illness were linked to care immediately. Of a total of 629
      patients eligible for ART at first CD4 count, 68% initiated ART within 3 months.
      Among those not eligible for ART, only 46% of patients sought subsequent CD4
      count in time. Multivariate logistic regression analysis revealed that patients
      with initial CD4 count of 350-500 cells/cu mm (OR: 2, 95% CI: 1.1-3.5) and >500
      cells/cu mm (OR: 2.1, 95% CI: 1.2-3.7) were less likely to do subsequent CD4 test
      on time as compared to those with CD4 < 50 cells/cu mm. Among patients not
      eligible for ART, those having >12 years of education (OR: 0.4, 95% CI: 0.2-0.9)
      were more likely to have timely uptake of subsequent CD4 count. Among ART
      eligible patients, being an unskilled laborer (OR: 2.2, 95% CI: 1.1-4.2)
      predicted lower uptake. The study highlights a long delay from HIV diagnosis to
      linkage and further attrition during pre-ART and ART phases. It identifies need
      for newer approaches aimed at timely linkage and continued retention for patients
      with low education, unskilled laborers, and importantly, asymptomatic patients. 

PMID- 25559638
TI  - Impact of water content and temperature on the degradation of Cry1Ac protein in
      leaves and buds of Bt cotton in the soil.
AB  - Determining the influence of soil environmental factors on degradation of Cry1Ac
      protein from Bt cotton residues is vital for assessing the ecological risks of
      this commercialized transgenic crop. In this study, the degradation of Cry1Ac
      protein in leaves and in buds of Bt cotton in soil was evaluated under different
      soil water content and temperature settings in the laboratory. An exponential
      model and a shift-log model were used to fit the degradation dynamics of Cry1Ac
      protein and estimate the DT50 and DT90 values. The results showed that Cry1Ac
      protein in the leaves and buds underwent rapid degradation in the early stage
      (before day 48), followed by a slow decline in the later stage under different
      soil water content and temperature. Cry1Ac protein degraded the most rapidly in
      the early stage at 35 degrees C with 70% soil water holding capacity. The DT50
      values were 12.29 d and 10.17 d and the DT90 values were 41.06 d and 33.96 d in
      the leaves and buds, respectively. Our findings indicated that the soil
      temperature was a major factor influencing the degradation of Cry1Ac protein from
      Bt cotton residues. Additionally, the relative higher temperature (25 degrees C
      and 35 degrees C) was found to be more conducive to degradation of Cry1Ac protein
      in the soil and the greater water content (100%WHC) retarded the process. These
      findings suggested that under appropriate soil temperature and water content,
      Cry1Ac protein from Bt cotton residues will not persist and accumulate in soil. 

PMID- 25559640
TI  - Terahertz-field-induced nonlinear electron delocalization in Au nanostructures.
AB  - Improved control over the electromagnetic properties of metal nanostructures is
      indispensable for the development of next-generation integrated nanocircuits and
      plasmonic devices. The use of terahertz (THz)-field-induced nonlinearity is a
      promising approach to controlling local electromagnetic properties. Here, we
      demonstrate how intense THz electric fields can be used to modulate electron
      delocalization in percolated gold (Au) nanostructures on a picosecond time scale.
      We prepared both isolated and percolated Au nanostructures deposited on high
      resistivity Si(100) substrates. With increasing the applied THz electric fields,
      large opacity in the THz transmission spectra takes place in the percolated
      nanostructures; the maximum THz-field-induced transmittance difference, 50% more,
      is reached just above the percolation threshold thickness. Fitting the
      experimental data to a Drude-Smith model, we found furthermore that the
      localization parameter and the damping constant strongly depend on the applied
      THz-field strength. These results show that ultrafast nonlinear electron
      delocalization proceeds via strong electric field of THz pulses; the intense THz
      electric field modulates the backscattering rate of localized electrons and
      induces electron tunneling between Au nanostructures across the narrow insulating
      bridges without any material breakdown. 

PMID- 25559641
TI  - Long-term sustained release of salicylic acid from cross-linked biodegradable
      polyester induces a reduced foreign body response in mice.
AB  - There has been a continuous surge toward developing new biopolymers that exhibit
      better in vivo biocompatibility properties in terms of demonstrating a reduced
      foreign body response (FBR). One approach to mitigate the undesired FBR is to
      develop an implant capable of releasing anti-inflammatory molecules in a
      sustained manner over a long time period. Implants causing inflammation are also
      more susceptible to infection. In this article, the in vivo biocompatibility of a
      novel, biodegradable salicylic acid releasing polyester (SAP) has been
      investigated by subcutaneous implantation in a mouse model. The tissue response
      to SAP was compared with that of a widely used biodegradable polymer, poly(lactic
      acid-co-glycolic acid) (PLGA), as a control over three time points: 2, 4, and 16
      weeks postimplantation. A long-term in vitro study illustrates a continuous,
      linear (zero order) release of salicylic acid with a cumulative mass percent
      release rate of 7.34 * 10(-4) h(-1) over ~1.5-17 months. On the basis of
      physicochemical analysis, surface erosion for SAP and bulk erosion for PLGA have
      been confirmed as their dominant degradation modes in vivo. On the basis of the
      histomorphometrical analysis of inflammatory cell densities and collagen
      distribution as well as quantification of proinflammatory cytokine levels (TNF
      alpha and IL-1beta), a reduced foreign body response toward SAP with respect to
      that generated by PLGA has been unambiguously established. The favorable in vivo
      tissue response to SAP, as manifest from the uniform and well-vascularized
      encapsulation around the implant, is consistent with the decrease in inflammatory
      cell density and increase in angiogenesis with time. The above observations,
      together with the demonstration of long-term and sustained release of salicylic
      acid, establish the potential use of SAP for applications in improved matrices
      for tissue engineering and chronic wound healing. 

PMID- 25559642
TI  - Inclusion probability with dropout: an operational formula.
AB  - In forensic genetics, a mixture of two or more contributors to a DNA profile is
      often interpreted using the inclusion probabilities theory. In this paper, we
      present a general formula for estimating the probability of inclusion (PI, also
      known as the RMNE probability) from a subset of visible alleles when dropouts are
      possible. This one-locus formula can easily be extended to multiple loci using
      the cumulative probability of inclusion. We show that an exact formulation
      requires fixing the number of contributors, hence to slightly modify the classic
      interpretation of the PI. We discuss the implications of our results for the
      enduring debate over the use of PI vs likelihood ratio approaches within the
      context of low template amplifications.

PMID- 25559643
TI  - Promiscuous 2-aminothiazoles (PrATs): a frequent hitting scaffold.
AB  - We have identified a class of molecules, known as 2-aminothiazoles (2-ATs), as
      frequent-hitting fragments in biophysical binding assays. This was exemplified by
      4-phenylthiazol-2-amine being identified as a hit in 14/14 screens against a
      diverse range of protein targets, suggesting that this scaffold is a poor
      starting point for fragment-based drug discovery. This prompted us to analyze
      this scaffold in the context of an academic fragment library used for fragment
      based drug discovery (FBDD) and two larger compound libraries used for high
      throughput screening (HTS). This analysis revealed that such "promiscuous 2
      aminothiazoles" (PrATs) behaved as frequent hitters under both FBDD and HTS
      settings, although the problem was more pronounced in the fragment-based studies.
      As 2-ATs are present in known drugs, they cannot necessarily be deemed
      undesirable, but the combination of their promiscuity and difficulties associated
      with optimizing them into a lead compound makes them, in our opinion, poor
      scaffolds for fragment libraries. 

PMID- 25559644
TI  - A magnetic polyaniline nanohybrid for MR imaging and redox sensing of cancer
      cells.
AB  - A synthetic process for constructing an organo-metal nanohybrid is described.
      This process uses polyaniline as a ligand in order to fabricate magnetic
      nanoparticles. This nanohybrid shows imaging potential uses as a magnetic
      resonance imaging contrast agent and a redox-sensing probe simultaneously both in
      vitro and in vivo.

PMID- 25559646
TI  - Correction to carbon nanohoops: excited singlet and triplet behavior of [9]- and
      [12]-cycloparaphenylene.

PMID- 25559645
TI  - Therapeutic management and evolution of chronic hepatitis B: does HIV still have
      an impact? The EPIB 2012 study.
AB  - BACKGROUND & AIMS: To compare the management of chronic hepatitis B (CHB) and its
      evolution over time in currently followed HIV-positive and HIV-negative patients.
      METHODS: A total of 709 consecutive patients with past or present positive HBs
      antigenemia seen in October 2012 in 19 French participating centres were
      included. The data were retrospectively collected from the first visit onwards
      through standardized questionnaires. RESULTS: Chronic hepatitis B was less often
      assessed in the 299 HIV-positive patients, who were older, more likely to be
      male, excessive alcohol drinkers and HBe antigen-, HCV- and HDV-positive. They
      were also followed up for a longer time (11.3 +/-8.8 vs. 8.6 +/-6.9 years, P <
      10(-3) ) and were more frequently treated for HBV (95.3% vs. 56.8%, P < 10(-3) ).
      HBV was undetectable at the last visit in 80.8% of HIV-positive vs. 55.1% of HIV
      negative patients (P < 10(-3) ). In multivariate analyses, undetectable HBV was
      significantly associated with older age, lower baseline HBV DNA, longer HBV
      therapy and no previous lamivudine monotherapy, but not with HIV. Cirrhosis was
      associated with age, male gender, Asian origin, alcoholism, HCV, HDV, but not
      with HIV infection. Hepatocellular carcinoma, less frequently observed in HIV
      positive patients (0.7% vs. 4.7%, P = 0.002), was positively associated with age,
      male gender, cirrhosis and negatively associated with HIV infection (OR 0.15,
      95%CI 0.03-0.67, P = 0.01). CONCLUSIONS: Although the assessment of CHB still has
      to be improved in HIV-positive patients, the negative impact of HIV on the
      virological, histological and clinical evolution of CHB seems to be disappearing,
      probably because of the immunovirological impact of HAART and the more frequent
      and longer use of HBV therapy.

PMID- 25559647
TI  - Inpatient alcohol withdrawal syndrome.
AB  - A 55-year-old man was admitted for a femur fracture; an alcohol fetor was noted
      on admission. The following day, the patient began to experience tremors and
      nervousness. Intravenous haloperidol was administered. Shortly afterwards, the
      patient experienced two generalized seizures and then began to experience
      delirium and uncontrollable agitation. The patient was diagnosed with alcohol
      withdrawal syndrome; high doses of intravenous midazolam were prescribed and
      infused. A few hours later, the patient presented signs of respiratory
      depression, requiring a transfer to the intensive care unit. After a review of
      the medical history, it was determined that the patient had been admitted on 3
      previous occasions due to alcohol withdrawal and had progressed to delirium
      tremens after experiencing seizures. Can the risk of alcohol withdrawal syndrome
      and the need for prophylactic treatment be assessed on admission? Were
      appropriate monitoring and treatment measures employed? Would it have been
      possible to change his outcome? 

PMID- 25559648
TI  - Extensive cutaneous epidermoid carcinoma with brain exposure.

PMID- 25559649
TI  - Skin necrosis as a complication of bronchial artery embolization.

PMID- 25559650
TI  - Immunophenotypic characterization of human glioblastoma stem cells: correlation
      with clinical outcome.
AB  - Recently, glioma stem cells have been identified as the main cause of glioma
      propagation and recurrence and a number of several cell markers have been
      indicated as putative GSC markers. In the present work, a retrospective study to
      evaluate the prognostic potential of ability to generate GSCs in our series of 15
      glioblastoma patients is described. beta-tubulin III, nestin, CD133, GFAP, and
      SOX-2 marker expression, both in primary GBM cultures and in respective
      glioblastoma stem cells (GSCs), was evaluated by flow cytometric analysis. Our
      results demonstrated various expression levels of these markers in both cell
      cultures; of note, only those cells expressing SOX-2 at greater than 30% levels
      were able to produce in vitro neurospheres. Moreover, statistical analysis
      revealed that the GSCs generation negatively affected overall survival (OS) (P =
      0.000) and progression-free survival (PFS) (P = 0.001). In addition, a very poor
      OS (P = 0.000) and PFS (P = 0.000) were observed among patients whose tumors
      expressed Ki67, evaluated by immunohistochemistry, and showed the ability to
      generate in vitro GSCs. Overall, the results suggest that in vitro GSCs
      generation associated to the expression of Ki67 and SOX-2 may be useful to
      identify patients at risk of disease progression.

PMID- 25559652
TI  - Speeded naming or naming speed? The automatic effect of object speed on
      performance.
AB  - We test the hypothesis that naming an object depicted in a picture and reading
      aloud an object's name are affected by the object's speed. We contend that the
      mental representations of everyday objects and situations include their speed,
      and that the latter influences behavior in instantaneous and systematic ways. An
      important corollary is that high-speed objects are named faster than low-speed
      objects, although object speed is irrelevant to the naming task at hand. The
      results of a series of 7 studies with pictures and words support these
      predictions.

PMID- 25559651
TI  - Assessment of right ventricular functional recovery after acute myocardial
      infarction by 2D speckle-tracking echocardiography.
AB  - To assess the pattern of right ventricular (RV) functional recovery in a cohort
      of patients with successful reperfusion of a first episode of acute myocardial
      infarction (AMI) with 2D speckle-tracking echocardiography and cardiac magnetic
      resonance imaging (CMR). Ninety-five revascularized AMI patients were
      prospectively included (56.8 +/- 11.1 years, 48 inferior, 47 anterior). RV
      function was assessed by echocardiography and CMR within the initial 72 h and 6
      months later. A RV global strain was calculated while averaging strain values
      from septal, lateral and inferior walls. At the acute phase, RVEFCMR was lower in
      inferior than in anterior AMI patients (52.5 +/- 6.8 vs. 56.0 +/- 4.8, p =
      0.006). Similarly, RV global, inferior and lateral strains were lower in inferior
      MI patients (p < 0.001 for all) whereas septal strain was not significantly
      different across groups. At 6 months, RVEFCMR and all strain parameters improved
      compared to baseline. Improvements were more substantial for patients with
      inferior than with anterior MI. RV parameters ultimately reached similar levels
      in the two groups at 6 months except for inferior strain which remained lower in
      patients with inferior MI (-24.5 +/- 6.5 vs. -27.5 +/- 5.4, p = 0.03). In low
      risk patients after AMI, RV function ultimately recovered over the 6 months of
      follow up. Higher levels of both initial impairment and subsequent recovery were
      observed for inferior MI. Although RV function was relatively preserved in these
      patients, RV strain analysis revealed a persistent impairment of RV inferior
      strain in patients with inferior MI, which may not be identified by RVEFCMR or
      conventional echocardiographic parameters.

PMID- 25559653
TI  - Reward guides attention to object categories in real-world scenes.
AB  - Reward is thought to motivate animal-approach behavior in part by automatically
      facilitating the perceptual processing of reward-associated visual stimuli.
      Studies have demonstrated this effect for low-level visual features such as color
      and orientation. However, outside of the laboratory, it is rare that low-level
      features uniquely characterize objects relevant for behavior. Here, we test
      whether reward can prime representations at the level of object category.
      Participants detected category exemplars (cars, trees, people) in briefly
      presented photographs of real-world scenes. On a subset of trials, successful
      target detection was rewarded and the effect of this reward was measured on the
      subsequent trial. Results show that rewarded selection of a category exemplar
      caused other members of this category to become visually salient, disrupting
      search when subsequently presented as distractors. It is important to note that
      this occurred even when there was little opportunity for the repetition of visual
      features between examples, with the rewarded selection of a human body increasing
      the salience of a subsequently presented face. Thus, selection of a category
      example appears to activate representations of prototypical category
      characteristics even when these are not present in the stimulus. In this way,
      reward can guide attention to categories of stimuli even when individual examples
      share no visual characteristics.

PMID- 25559654
TI  - Affective processing requires awareness.
AB  - Studies using backward masked emotional stimuli suggest that affective processing
      may occur outside visual awareness and imply primacy of affective over semantic
      processing, yet these experiments have not strictly controlled for the
      participants' awareness of the stimuli. Here we directly compared the primacy of
      affective versus semantic categorization of biologically relevant stimuli in 5
      experiments (n = 178) using explicit (semantic and affective discrimination;
      Experiments 1-3) and implicit (semantic and affective priming; Experiments 4-5)
      measures. The same stimuli were used in semantic and affective tasks. Visual
      awareness was manipulated by varying exposure duration of the masked stimuli, and
      subjective level of stimulus awareness was measured after each trial using a 4
      point perceptual awareness scale. When participants reported no awareness of the
      stimuli, semantic and affective categorization were at chance level and priming
      scores did not differ from zero. When participants were even partially aware of
      the stimuli, (a) both semantic and affective categorization could be performed
      above chance level with equal accuracy, (b) semantic categorization was faster
      than affective categorization, and (c) both semantic and affective priming were
      observed. Affective categorization speed was linearly dependent on semantic
      categorization speed, suggesting dependence of affective processing on semantic
      recognition. Manipulations of affective and semantic categorization tasks
      revealed a hierarchy of categorization operations beginning with basic-level
      semantic categorization and ending with superordinate level affective
      categorization. We conclude that both implicit and explicit affective and
      semantic categorization is dependent on visual awareness, and that affective
      recognition follows semantic categorization.

PMID- 25559655
TI  - Adverse drug reaction: a possible case of glimepiride-induced syndrome of
      inappropriate antidiuretic hormone secretion.

PMID- 25559656
TI  - Outcome following local-regional recurrence in women with early-stage breast
      cancer: impact of biologic subtype.
AB  - Local-regional recurrence (LRR) after breast-conserving therapy (BCT) can result
      in distant metastasis and decreased disease-free survival (DFS). This study
      examines factors associated with DFS following LRR. The initial population
      included 2,233 consecutive women who underwent BCT from 1998 to 2007. Biologic
      subtype was approximated using a combination of estrogen receptor (ER),
      progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and
      tumor grade. Cumulative incidence of DFS after LRR was calculated. The
      association of clinical, pathologic, and treatment parameters with DFS was
      evaluated using a Cox regression model. At a median follow-up of 105 months, 82
      patients (3.7%) had a LRR. Of these, 66 (80%) were in-breast and 16 (20%)
      involved the ipsilateral lymph nodes. Twenty patients subsequently developed
      distant metastases. Five-year DFS after initial recurrence was 69.6% for the
      overall cohort. On univariate analysis, triple-negative disease (ER/PR/HER2
      negative, TNBC) was associated with reduced DFS (HR = 3.8; 95% CI: 1.8-8.1; p <
      0.001). Other factors associated with reduced DFS were larger tumor size (HR =
      1.3; 95% CI: 1.03-1.6; p = 0.02), shorter interval from initial diagnosis to LRR
      (HR = 0.98 per month; 95% CI: 0.97-0.99; p = 0.02), and no salvage surgery (HR =
      0.2; 95% CI: 0.09-0.5; p = 0.001). On multivariate analysis, TNBC remained the
      most significant factor associated with reduced DFS (HR = 4.8; 95% CI: 2.25-10.4;
      p < 0.001). Compared to women with luminal A disease, those with TNBC had
      significantly worse DFS (37.5% versus 88.3% at 5 years; p < 0.001). Women with
      TNBC who developed LRR were at high risk of subsequent recurrence. Efforts should
      be targeted toward both preventing initial recurrence and decreasing subsequent
      metastasis.

PMID- 25559657
TI  - Cerebrospinal fluid total prion protein: a potential in vivo marker of cerebral
      prion pathology.

PMID- 25559658
TI  - Selective and contagious prosocial resource donation in capuchin monkeys,
      chimpanzees and humans.
AB  - Prosocial acts benefitting others are widespread amongst humans. By contrast,
      chimpanzees have failed to demonstrate such a disposition in several studies,
      leading some authors to conclude that the forms of prosociality studied evolved
      in humans since our common ancestry. However, similar prosocial behavior has
      since been documented in other primates, such as capuchin monkeys. Here, applying
      the same methodology to humans, chimpanzees, and capuchins, we provide evidence
      that all three species will display prosocial behavior, but only in certain
      conditions. Fundamental forms of prosociality were age-dependent in children,
      conditional on self-beneficial resource distributions even at age seven, and
      conditional on social or resource configurations in chimpanzees and capuchins. We
      provide the first evidence that experience of conspecific companions' prosocial
      behavior facilitates prosocial behavior in children and chimpanzees. Prosocial
      actions were manifested in all three species following rules of contingency that
      may reflect strategically adaptive responses. 

PMID- 25559660
TI  - [Patient knowledge about their treatment according to the therapeutic class:
      misplaced antiplatelet].

PMID- 25559659
TI  - Improved oxidative status in major abdominal surgery patients after N-acetyl
      cystein supplementation.
AB  - BACKGROUND: Increased levels of reactive oxygen species during and after surgery
      may affect inflammatory response, post-operative adhesion molecule formation, and
      hemodynamic stability. The glutathione redox cycle is an important regulator in
      oxidative stress and its reduced forms scavenge free radicals. N-acetyl cysteine,
      a precursor of reduced glutathione, is considered as a potentially therapeutic
      wide spectrum agent in clinical practice. We therefore examined whether N-acetyl
      cysteine improves some biochemical parameters in cancer patients undergoing major
      abdominal surgery. METHODS: Thirty-three patients diagnosed with pancreas,
      stomach, rectum, colon malignancies, and undergoing major abdominal surgery at
      Ankara Numune Training and Research Hospital were randomly divided into two
      groups; control (CON) and N-acetyl cysteine (NAC). The NAC group had 1,200 mg N
      acetyl cysteine starting two days before the operation day, in addition to
      isonitrogenous and isocaloric total parenteral nutrition of 1.2 g/kg protein, 25
      kcal/kg, and 60:40 carbohydrate/fat ratio. Blood and urine samples were drawn two
      days before the operation, on operation day, and on the first, third, and fifth
      days post-operation. RESULTS: Plasma malondialdehyde was significantly lower in
      the NAC group (P < 0.001). N-acetyl cysteine treatment did not affect plasma
      levels of vitamin A, C or E. The NAC group exhibited a higher ratio of reduced
      glutathione to oxidised glutathione (P = 0.019). Urinary nitrate level was also
      significantly lower in the NAC group (P = 0.016). CONCLUSION: The study
      demonstrated the clinical importance of N-acetyl cysteine supplementation on
      antioxidant parameters in abdominal surgery patients. In these patients N-acetyl
      cysteine and vitamin administration can be considered as an effective method for
      improvement of oxidative status.

PMID- 25559661
TI  - Large-strain, multiform movements from designable electrothermal actuators based
      on large highly anisotropic carbon nanotube sheets.
AB  - Many electroactive polymer (EAP) actuators use diverse configurations of carbon
      nanotubes (CNTs) as pliable electrodes to realize discontinuous, agile movements,
      for CNTs are conductive and flexible. However, the reported CNT-based EAP
      actuators could only accomplish simple, monotonous actions. Few actuators were
      extended to complex devices because efficiently preparing a large-area CNT
      electrode was difficult, and complex electrode design has not been carried out.
      In this work, we successfully prepared large-area CNT paper (buckypaper, BP)
      through an efficient approach. The BP is highly anisotropic, strong, and suitable
      as flexible electrodes. By means of artful graphic design and processing on BP,
      we fabricated various functional BP electrodes and developed a series of BP
      polymer electrothermal actuators (ETAs). The prepared ETAs can realize various
      controllable movements, such as large-stain bending (>180 degrees ), helical
      curling (~ 630 degrees ), or even bionic actuations (imitating human-hand
      actions). These functional and interesting movements benefit from flexible
      electrode design and the anisotropy of BP material. Owing to the advantages of
      low driving voltage (20-200 V), electrolyte-free and long service life (over
      10000 times), we think the ETAs will have great potential applications in the
      actuator field.

PMID- 25559662
TI  - Impaired autophagy affects acid alpha-glucosidase processing and enzyme
      replacement therapy efficacy in late-onset glycogen storage disease type II.

PMID- 25559663
TI  - Discovery of small protein complexes from PPI networks with size-specific
      supervised weighting.
AB  - The prediction of small complexes (consisting of two or three distinct proteins)
      is an important and challenging subtask in protein complex prediction from
      protein-protein interaction (PPI) networks. The prediction of small complexes is
      especially susceptible to noise (missing or spurious interactions) in the PPI
      network, while smaller groups of proteins are likelier to take on topological
      characteristics of real complexes by chance. We propose a two-stage approach, SSS
      and Extract, for discovering small complexes. First, the PPI network is weighted
      by size-specific supervised weighting (SSS), which integrates heterogeneous data
      and their topological features with an overall topological isolatedness feature.
      SSS uses a naive-Bayes maximum-likelihood model to weight the edges with two
      posterior probabilities: that of being in a small complex, and of being in a
      large complex. The second stage, Extract, analyzes the SSS-weighted network to
      extract putative small complexes and scores them by cohesiveness-weighted
      density, which incorporates both small-co-complex and large-co-complex weights of
      edges within and surrounding the complexes. We test our approach on the
      prediction of yeast and human small complexes, and demonstrate that our approach
      attains higher precision and recall than some popular complex prediction
      algorithms. Furthermore, our approach generates a greater number of novel
      predictions with higher quality in terms of functional coherence.

PMID- 25559665
TI  - Porcine complement regulatory protein CD46 and heparan sulfates are the major
      factors for classical swine fever virus attachment in vitro.
AB  - Classical swine fever virus (CSFV) is the causative agent of a severe multi
      systemic disease of pigs. While several aspects of virus-host-interaction are
      known, the early steps of infection remain unclear. For the closely related
      bovine viral diarrhea virus (BVDV), a cellular receptor is known: bovine
      complement regulatory protein CD46. Given that these two pestiviruses are closely
      related, porcine CD46 is also a candidate receptor for CSFV. In addition to CD46,
      cell-culture-adapted CSFV strains have been shown to use heparan sulfates as an
      additional cellular factor. In the present study, the interaction of field-type
      and cell-culture-adapted CSFV with a permanent porcine cell line or primary
      macrophages was assessed using anti-porcine CD46 monoclonal antibodies and a
      heparan-sulfate-blocking compound, DSTP-27. The influence of receptor blocking
      was assessed using virus titration and quantitative PCR. Treatment of cells with
      monoclonal antibodies against porcine CD46 led to a reduction of viral growth in
      both cell types. The effect was most pronounced with field-type CSFV. The
      blocking could be enhanced by addition of DSTP-27, especially for cell-culture
      adapted CSFV. The combined use of both blocking agents led to a significant
      reduction of viral growth but was also not able to abolish infection completely.
      The results obtained in this study showed that both porcine CD46 and heparan
      sulfates play a major role in the initial steps of CSFV infection. Additional
      receptors might also play a role for attachment and entry; however, their impact
      is obviously limited in vitro in comparison to CD46 and heparan sulfates.

PMID- 25559664
TI  - Use of acetochlor and cancer incidence in the Agricultural Health Study.
AB  - Since its registration in 1994 acetochlor has become a commonly used herbicide in
      the US, yet no epidemiologic study has evaluated its carcinogenicity in humans.
      We evaluated the use of acetochlor and cancer incidence among licensed pesticide
      applicators in the Agricultural Health Study. In telephone interviews
      administered during 1999-2005, participants provided information on acetochlor
      use, use of other pesticides and additional potential confounders. We used
      Poisson regression to estimate relative risks (RR) and 95% confidence intervals
      (95% CI) for cancers that occurred from the time of interview through 2011 in
      Iowa and 2010 in North Carolina. Among 33,484 men, there were 4,026 applicators
      who used acetochlor and 3,234 incident cancers, with 304 acetochlor-exposed
      cases. Increased risk of lung cancer was observed among acetochlor users (RR =
      1.74; 95% CI: 1.07-2.84) compared to nonusers, and among individuals who reported
      using acetochlor/atrazine product mixtures (RR = 2.33; 95% CI: 1.30-4.17),
      compared to nonusers of acetochlor. Colorectal cancer risk was significantly
      elevated among the highest category of acetochlor users (RR = 1.75; 95% CI: 1.08
      2.83) compared to never users. Additionally, borderline significantly increased
      risk of melanoma (RR = 1.61; 95% CI: 0.98-2.66) and pancreatic cancer (RR = 2.36;
      95% CI: 0.98-5.65) were observed among acetochlor users. The associations between
      acetochlor use and lung cancer, colorectal cancer, melanoma and pancreatic cancer
      are suggestive, however the lack of exposure-response trends, small number of
      exposed cases and relatively short time between acetochlor use and cancer
      development prohibit definitive conclusions.

PMID- 25559666
TI  - Interaction between Nef and INI1/SMARCB1 augments replicability of HIV-1 in
      resting human peripheral blood mononuclear cells.
AB  - A central feature of HIV-1 infection is the inability of entering virus to
      integrate into chromosomes of resting T lymphocytes unless they are mitogenically
      activated. In contrast, SIVpbj1.9 replicates in initially resting T lymphocytes
      by activating infected cells. Previous reports have shown that a difference in
      Nef-mediated T cell activation between HIV-1 and SIVpbj1.9 plays a critical role
      in the differing abilities of these viruses to replicate in resting lymphocytes.
      However, the molecular details of these differences are still unclear. Here, we
      show that infection with a chimeric virus, HSIVnef, which harbors the 5' 308
      nucleotides of SIVpbj1.9 nef in place of the 5' 221 nucleotides of HIV-1 nef in
      the HIV-1 proviral backbone, resulted in integration of the provirus into host
      chromosomes without mitogenic activation and thereby replication in resting human
      PBMCs (hPBMCs). These results indicate that Nef is an essential viral determinant
      for the integration of provirus into host chromosomes in resting T cells. Using
      the yeast two-hybrid system, we identified integrase interactor-1 (INI1/SMARCB1)
      as a cellular factor that is involved in the integration process via interaction
      with Nef. Although INI1 interacted with both SIVpbj1.9 and HIV-1 Nefs, SIVpbj1.9
      Nef, but not HIV-1 Nef, enhanced proviral integration into host DNA. Furthermore,
      mutational analysis revealed that the basic-amino-acid-rich amino-terminal domain
      in SIVpbj1.9 Nef is crucial for interaction with INI1 and virus replication in
      resting hPBMCs. Taken together, these data indicate that Nef is a critical viral
      protein for incorporating nascent proviral DNA into host chromosomes in resting
      PBMCs and that this occurs through interaction with INI1. This elucidates the
      basis for replication of the integrated provirus when the host cell is in a
      resting state.

PMID- 25559667
TI  - Complete genome sequence of a filamentous bacteriophage, RS611, that infects the
      phytopathogen Ralstonia solanacearum.
AB  - Filamentous bacteriophage RS611 (phiRS611), which infects the phytopathogen
      Ralstonia solanacearum, had a circular single-stranded DNA genome that was
      characterized as an Ff-type phage belonging to the family Inoviridae. The
      phiRS611 genome was composed of 6386 bases with a G + C content of 62.1 % and
      contained 11 putative open reading frames. The phiRS611 genome showed high
      similarity to those of Ralstonia phages RSS0 and RSS1. However, approximately 900
      nucleotide deletions were found in the region corresponding to open reading
      frames 10 and 11 of phiRSS0 and phiRSS1.

PMID- 25559668
TI  - Sequencing and generation of an infectious clone of the pathogenic goose
      parvovirus strain LH.
AB  - In this study, the complete genome of the virulent strain LH of goose parvovirus
      (GPV) was sequenced and cloned into the pBluescript II (SK) plasmid vector.
      Sequence alignments of the inverted terminal repeats (ITR) of GPV strains
      revealed a common 14-nt-pair deletion in the stem of the palindromic structure in
      the LH strain and three other strains isolated after 1982 when compared to three
      GPV strains isolated earlier than that time. Transfection of 11-day-old
      embryonated goose eggs with the plasmid pLH, which contains the entire genome of
      strain LH, resulted in successful rescue of the infectious virus. Death of
      embryos after transfection via the chorioallantoic membrane infiltration route
      occurred earlier than when transfection was done via the allantoic cavity
      inoculation route. The rescued virus exhibited virulence similar to that of its
      parental virus, as evaluated by the mortality rate in goslings. Generation of the
      pathogenic infectious clone provides us with a powerful tool to elucidate the
      molecular pathogenesis of GPV in the future.

PMID- 25559669
TI  - Role of cell death in the propagation of PrP(Sc) in immune cells.
AB  - A number of studies have suggested that macrophages, dendritic cells, and
      follicular dendritic cells play an important role in the propagation of PrP(Sc).
      Both accumulation and proteolysis of PrP(Sc) have been demonstrated in peripheral
      macrophages. Macrophages may act as reservoirs for PrP(Sc) particles if the cells
      die during transient PrP(Sc) propagation. However, whether cell death plays a
      role in PrP(Sc) propagation in macrophages remains unclear. In this study, we
      investigated the possibility of propagation and transmission of PrP(Sc) between
      dead immune cells and living neural cells. We found that under specific
      conditions, transient PrP(Sc) propagation occurs in dead cells, indicating that
      interaction between PrP(C) and PrP(Sc) on plasma membrane lipid rafts might be
      important for PrP(Sc) propagation. Co-culturing of killed donor PrP(Sc)-infected
      macrophages with recipient N2a-3 neuroblastoma cells accelerated PrP(Sc)
      transmission. Our results suggest that cell death may play an important role in
      PrP(Sc) propagation, whereas transient PrP(Sc) propagation in macrophages has
      little effect on PrP(Sc) transmission.

PMID- 25559670
TI  - Enterovirus C strains circulating in Nigeria and their contribution to the
      emergence of recombinant circulating vaccine-derived polioviruses.
AB  - Between 2005 and 2011, 23 lineages of circulating vaccine-derived polioviruses
      (cVDPVs) were detected in Nigeria with nonstructural region (NSR) of non-polio
      enterovirus C (NPEV-C) origin. However, no information exists on NPEV-C strains
      recombining with oral poliovirus type 2 vaccine strains (OPV2) to make type 2
      cVDPVs (cVDPV2s) in Nigeria. This study was therefore designed to investigate the
      probable contribution of NPEV-Cs recently isolated in the region to the emergence
      of cVDPV2s. Eleven enterovirus C (EV-C) strains (8 NPEV-Cs and 3 PV2s) previously
      isolated by the authors were analysed in this study. All 11 isolates were assayed
      for cell-line-dependent growth restriction in four cell lines (LLC-MK2, MCF-7, RD
      and L20B). Subsequently, the isolates were subjected to RT-PCR specific for VP1
      and 3Dpol/3'-UTR of EV-C. All PCR products were sequenced, and phylogenetic
      analysis was performed. All eight NPEV-Cs replicated exclusively in the MCF-7
      cell line, while the three PV2s replicated in all four cell lines. The eight NPEV
      Cs were identified as CVA13 (7 isolates) and CVA20 (1 isolate) by VP1 analysis,
      while all 11 isolates were confirmed to be EV-Cs by 3Dpol/3'-UTR analysis. In
      addition, phylogeny violations suggested that some cVDPVs might have recombined
      with common ancestors of the NPEV-Cs described in this study. This was confirmed
      by the scatter plot of divergence in VP1 against that of 3Dpol/3'-UTR sequences
      for pairs of isolates. The results of this study showed that the NSR of unknown
      origin found in cVDPVs from the region might have come from NPEV-Cs (e.g., CVA13
      and CVA20) circulating in Nigeria.

PMID- 25559673
TI  - Identification of a picornavirus from chickens with transmissible viral
      proventriculitis using metagenomic analysis.
AB  - Transmissible viral proventriculitis (TVP), an infectious disease in chickens, is
      responsible for economic losses in the commercial poultry industry. The major
      etiologic agent, however, is unknown. Using metagenomics, we compared the
      diversity of viruses present in proventriculus samples from flocks diagnosed with
      TVP to those of healthy flocks in South Korea between 2003 and 2012. Each sample
      had a mean of 21,538,726 sequence reads generated by high-throughput sequencing,
      with a mean length of 160 nt. Enrichment in viral sequences suggested that at
      least three viruses were present in each TVP sample. Although we could not
      determine a pathogen of TVP that matched the known morphology, picornavirus
      sequences were present in all five disease samples, suggesting an association
      with TVP. The five samples yielded 1,045-1,720 bp contigs with 81-84 % nt
      sequence identity to turkey hepatitis virus (accession number: HM751199). Whole
      genome analysis indicated that the QIA01 strain of the novel picornavirus was
      similar to turkey hepatitis virus in the P2 and P3 regions (82.7 % nt and 95.5 %
      aa sequence identity), but different in the structural region and partial 2A
      peptides (56.2 % nt and 23.9 % aa sequence identity). In addition, the QIA01
      virus was similar (87.0 % nt and 95.6 % aa sequence identity) to chicken
      megrivirus, recently detected in chickens with malabsorption syndrome in Hungary.
      Our results are useful for understanding the genetic diversity of avian
      picornaviruses and for classifying chicken megrivirus as a pathogen affecting the
      digestive tract of chickens.

PMID- 25559671
TI  - Full genome characterization and phylogenetic analysis of hepatitis B virus in
      gibbons and a caretaker in Central Kalimantan, Indonesia.
AB  - Hepatitis B virus (HBV) from gibbons was characterized, and the possibility of
      horizontal transmission between gibbons and humans was examined in a gibbon
      rehabilitation center in Central Kalimantan, Indonesia. Ten gibbons that were
      positive for the hepatitis B surface antigen (HBsAg) on arrival and 13 caretakers
      for those gibbons were included in this study. The duration of stay at the
      rehabilitation center ranged from 1 to 10 years. Serological and molecular
      analyses were performed. Six gibbons were positive for HBsAg, whereas HBV DNA was
      detected in all ten of the gibbons sampled. On the other hand, HBsAg was detected
      in only 1 of the 13 caretakers. HBV samples from seven gibbons and from the one
      infected human were chosen for complete genome sequencing. A phylogenetic
      analysis revealed that the cluster of gibbon strains in this study was distinct
      from strains previously reported from other countries. In the pre-S1 region, we
      found a unique amino acid residue substitution (P89K), three insertions between
      T87 and L88 in the genomes of three gibbons, and a 33-nucleotide deletion at the
      start of pre-S1 that is common in non-human primates. The caretaker sample was
      identified as HBV subgenotype B3, the most common type in Indonesia. For the
      complete HBV sequences, the similarity between gibbons in this study and other
      non-human primate and human HBV isolates was 90-91.9 % and 85.5-89.6 %,
      respectively. In conclusion, the gibbon HBV genotype was influenced by geographic
      location and species. To the best of our knowledge, this is the first report
      characterizing the HBV genes and genomes of indigenous gibbons in Indonesia.

PMID- 25559672
TI  - First complete genome sequence of a capsicum chlorosis tospovirus isolate from
      Australia with an unusually large S RNA intergenic region.
AB  - The first complete genome sequence of capsicum chlorosis virus (CaCV) from
      Australia was determined using a combination of Illumina HiSeq RNA and Sanger
      sequencing technologies. Australian CaCV had a tripartite genome structure like
      other CaCV isolates. The large (L) RNA was 8913 nucleotides (nt) in length and
      contained a single open reading frame (ORF) of 8634 nt encoding a predicted RNA
      dependent RNA polymerase (RdRp) in the viral-complementary (vc) sense. The medium
      (M) and small (S) RNA segments were 4846 and 3944 nt in length, respectively,
      each containing two non-overlapping ORFs in ambisense orientation, separated by
      intergenic regions (IGR). The M segment contained ORFs encoding the predicted non
      structural movement protein (NSm; 927 nt) and precursor of glycoproteins (GP;
      3366 nt) in the viral sense (v) and vc strand, respectively, separated by a 449
      nt IGR. The S segment coded for the predicted nucleocapsid (N) protein (828 nt)
      and non-structural suppressor of silencing protein (NSs; 1320 nt) in the vc and v
      strand, respectively. The S RNA contained an IGR of 1663 nt, being the largest
      IGR of all CaCV isolates sequenced so far. Comparison of the Australian CaCV
      genome with complete CaCV genome sequences from other geographic regions showed
      highest sequence identity with a Taiwanese isolate. Genome sequence comparisons
      and phylogeny of all available CaCV isolates provided evidence for at least two
      highly diverged groups of CaCV isolates that may warrant re-classification of AIT
      Thailand and CP-China isolates as unique tospoviruses, separate from CaCV.

PMID- 25559674
TI  - Rapid and simultaneous detection of three major diarrhea-causing viruses by
      multiplex real-time nucleic acid sequence-based amplification.
AB  - Rotaviruses, noroviruses and astroviruses are the major viral pathogens leading
      to diarrhea worldwide. Epidemiological investigations of outbreaks associated
      with these viruses have been impeded by the lack of methods for quick diagnosis
      and detection. In the current study, a multiplex real-time nucleic acid sequence
      based amplification (RT-NASBA) system was developed for the simultaneous
      detection of rotavirus A/norovirus genogroup II/astrovirus. The specificity and
      sensitivity of the assay were compared with multiplex RT-PCR. The results showed
      that the multiplex RT-NASBA assay was established successfully, and robust
      signals could be observed in 10 minutes with high specificity. The limit of
      detection of the multiplex RT-NASBA assay was 7, 100, and 200 copies per reaction
      for rotavirus A, norovirus genogroup II, and astrovirus, respectively. The assay
      was thus 10 to 100 times more sensitive than multiplex RT-PCR. Clinical
      evaluation indicated that the assay was 100% concordant with multiplex RT-PCR and
      was reliable for the detection of both single infections and multiple infections
      in stool samples. To the best of our knowledge, this is the first multiplex RT
      NASBA assay established for the detection of three major diarrhea-causing
      viruses. This assay provides a valuable platform for the rapid, specific,
      sensitive and simultaneous diagnosis of these pathogens, especially in resource
      limited countries where expensive thermocycling equipment is not available. 

PMID- 25559675
TI  - Mining hidden knowledge for drug safety assessment: topic modeling of LiverTox as
      a case study.
AB  - BACKGROUND: Given the significant impact on public health and drug development,
      drug safety has been a focal point and research emphasis across multiple
      disciplines in addition to scientific investigation, including consumer
      advocates, drug developers and regulators. Such a concern and effort has led
      numerous databases with drug safety information available in the public domain
      and the majority of them contain substantial textual data. Text mining offers an
      opportunity to leverage the hidden knowledge within these textual data for the
      enhanced understanding of drug safety and thus improving public health. METHODS:
      In this proof-of-concept study, topic modeling, an unsupervised text mining
      approach, was performed on the LiverTox database developed by National Institutes
      of Health (NIH). The LiverTox structured one document per drug that contains
      multiple sections summarizing clinical information on drug-induced liver injury
      (DILI). We hypothesized that these documents might contain specific textual
      patterns that could be used to address key DILI issues. We placed the study on
      drug-induced acute liver failure (ALF) which was a severe form of DILI with
      limited treatment options. RESULTS: After topic modeling of the "Hepatotoxicity"
      sections of the LiverTox across 478 drug documents, we identified a hidden topic
      relevant to Hy's law that was a widely-accepted rule incriminating drugs with
      high risk of causing ALF in humans. Using this topic, a total of 127 drugs were
      further implicated, 77 of which had clear ALF relevant terms in the "Outcome and
      management" sections of the LiverTox. For the rest of 50 drugs, evidence
      supporting risk of ALF was found for 42 drugs from other public databases.
      CONCLUSION: In this case study, the knowledge buried in the textual data was
      extracted for identification of drugs with potential of causing ALF by applying
      topic modeling to the LiverTox database. The knowledge further guided
      identification of drugs with the similar potential and most of them could be
      verified and confirmed. This study highlights the utility of topic modeling to
      leverage information within textual drug safety databases, which provides new
      opportunities in the big data era to assess drug safety.

PMID- 25559676
TI  - Adductor canal compression syndrome: a forgotten disease.
AB  - Superficial femoral vessels entrapped at the level of the adductor canal are
      rarely described. We first report the case of a young patient who practices
      professional soccer, affected with superficial femoral vein and artery occlusion
      due to a hypertrophied vastus medialis and adductor magnus at the Hunter's canal
      outlet. A careful literature search through MedLine was performed to elucidate
      the fascinating aspect of this occurrence.

PMID- 25559677
TI  - 'Ice epidemic'? Trends in methamphetamine use from three Victorian surveillance
      systems.

PMID- 25559678
TI  - Factors associated with loss-to-follow-up during behavioral interventions and HIV
      testing cohort among men who have sex with men in Nanjing, China.
AB  - BACKGROUND: Behavioral interventions (BIs) remained the cornerstone of HIV
      prevention in resource-limited settings. One of the major concerns for such
      efforts is the loss-to-follow-up (LTFU) that threatens almost every HIV control
      program involving high-risk population groups. METHODS: To evaluate the factors
      associated with LTFU during BIs and HIV testing among men who have sex with men
      (MSM), 410 HIV sero-negatives MSM were recruited using respondent driven sampling
      (RDS) in Nanjing, China during 2008, they were further followed for 18 months. At
      baseline and each follow-up visits, each participant was counseled about various
      HIV risk-reductions BIs at a designated sexually transmitted infection (STI)
      clinic. RESULTS: Among 410 participants recruited at baseline, altogether 221
      (53.9%) were LTFU at the 18-month follow-up visit. Overall, 46 participants were
      found to be positive for syphilis infection at baseline while 13 participants
      were HIV sero-converted during the follow-up period. Increasing age was less
      (Adjusted Odds Ratio(aOR) of 0.90, 95% confidence Interval (CI) 0.86-0.94) and
      official residency of provinces other than Nanjing (AOR of 2.49, 95%CI 1.32
      4.71), lower level of education (AOR of 2.01, 95%CI 1.10-3.66) and small social
      network size (AOR of 1.75, 95%CI 1.09-2.80) were more likely to be associated
      with higher odds of LTFU. CONCLUSION: To improve retention in the programs for
      HIV control, counseling and testing among MSM in Nanjing, focused intensified
      intervention targeting those who were more likely to be LTFU, especially the
      young, less educated, unofficial residents of Nanjing who had smaller social
      network size, might be helpful.

PMID- 25559679
TI  - Triggering of stroke by ambient temperature variation: a case-crossover study in
      Maputo, Mozambique.
AB  - OBJECTIVES: The effect of ambient temperature as a stroke trigger is likely to
      differ by type of stroke and to depend on non-transient exposures that influence
      the risk of this outcome. We aimed to quantify the association between ambient
      temperature variation and stroke, according to clinical characteristics of the
      events, and other risk factors for stroke. METHODS: We conducted a case-crossover
      study based on a 1-year registry of the hospital admissions due to newly
      occurring ischemic and hemorrhagic stroke events in Maputo, Mozambique's capital
      city (N=593). The case-period was defined as the 7 days before the stroke event,
      which was compared to two control periods (14-21 days and 21-28 days before the
      event). We computed humidity- and precipitation-adjusted odds ratios (OR) and 95%
      confidence intervals (95%CI) using conditional logistic regression. RESULTS: An
      association between minimum temperature declines higher than 2.4  degrees C in
      any two consecutive days in the previous week and the occurrence of stroke was
      observed only for first events (OR=1.43, 95%CI: 1.15-1.76). Stronger and
      statistically significant associations were observed for hemorrhagic stroke
      (OR=1.50, 95%CI: 1.07-2.09) and among subjects not exposed to risk factors,
      including smoking, high serum cholesterol or atrial fibrillation. No differences
      in the effect of temperature were found according to the patients' vital status
      28 days after the event. CONCLUSIONS: First stroke events, especially of the
      hemorrhagic type, were triggered by declines in the minimum temperature between
      consecutive days of the preceding week.

PMID- 25559681
TI  - Autophagy and immunity.

PMID- 25559680
TI  - Lessons from gain- and loss-of-function models of pro-survival Bcl2 family
      proteins: implications for targeted therapy.
AB  - Cell survival depends on the maintenance of mitochondrial integrity controlled by
      a well-balanced interplay between anti- and pro-apoptotic B cell lymphoma 2
      (Bcl2) family members. Given their frequent deregulation in human pathologies,
      including autoimmunity and cancer, significant research efforts have increased
      our molecular understanding of how Bcl2 proteins control cell death. This has
      fostered the development of small non-peptidic compounds, so-called BH3-mimetics,
      that show excellent prospects of passing clinical trials and entering daily use
      for targeted therapy. Possible limitations in clinical application may, to a
      certain degree, be predicted from loss-of-function phenotypes gathered from
      studies using gene-modified mice that we attempt to summarize and discuss in this
      context. 

PMID- 25559682
TI  - Wisteria floribunda agglutinin positive human Mac-2-binding protein as a
      predictor of hepatocellular carcinoma development in chronic hepatitis C
      patients.
AB  - AIMS: Wisteria floribunda agglutinin (WFA)-positive human Mac-2-binding protein
      (WFA(+) -M2BP) is a new glycol marker related to liver fibrosis. The aim of the
      present study was to evaluate WFA(+) -M2BP as a predictor of hepatocellular
      carcinoma (HCC) development in patients with chronic hepatitis C. METHODS: This
      case-control study included 14 patients with chronic hepatitis C who developed
      HCC and 52controls, matched for age, gender, and fibrosis stage. WFA(+) -M2BP was
      measured at biopsy and follow-up. Time zero was set at the date of liver biopsy.
      RESULTS: WFA(+) -M2BP increased stepwise with progression of liver fibrosis (p <
      0.001). Cumulative incidence of HCC development was significantly higher in
      patients with WFA(+) -M2BP >=4.2 (p < 0.001) or in those with time-course changes
      in WFA(+) -M2BP (DeltaWFA(+) -M2BP/year) >=0.3 (p = 0.03). Multivariate analyses
      demonstrated that WFA(+) -M2BP >=4.2 [hazard ratio (HR): 4.1, 95% confidence
      interval (CI): 1.1-15, p = 0.04], DeltaWFA(+) -M2BP/year >=0.3 (HR: 5.5, 95% CI:
      1.5-19, p = 0.008), and AFP >=10 ng/ml (HR: 4.7, 95% CI: 1.1-19, p = 0.03) were
      independent predictive factors of HCC development. Based on these data, we
      developed a simple scoring system to predict HCC development using these three
      factors. Using these scores, patients were classified into four groups;
      cumulative incidence of HCC development significantly increased with increasing
      scores (p < 0.001). CONCLUSIONS: WFA(+) -M2BP measurements and time-course
      changes in WFA(+) -M2BP can be used to identify patients at high risk of HCC
      development. Real-time monitoring of WFA(+) -M2BP can be a novel predictor of HCC
      development.

PMID- 25559683
TI  - Anti-JC virus antibodies in rituximab-treated patients with neuromyelitis optica
      spectrum disorder.
AB  - Rituximab, a chimeric monoclonal anti-CD20 antibody, has been proposed to be
      effective for neuromyelitis optica spectrum disorder (NMOSD). A concern for
      developing progressive multifocal leukoencephalopathy (PML), which is caused by
      John Cunningham virus (JCV), has been suggested particularly in patients treated
      long term with rituximab. In this study, using a modified enzyme-linked
      immunosorbent assay with glutathione S-transferase-tagged VP1 as the antigen, we
      investigated the seroprevalence of anti-JCV antibodies among 78 Korean patients
      with NMOSD and the change in anti-JCV antibody serostatus following long-term
      rituximab treatment. The overall seroprevalence of anti-JCV antibodies was 69 %
      prior to rituximab administration. Over a mean of 4 years of repeated treatment
      with rituximab, no patient developed PML. Of 24 initially seronegative patients,
      none converted into seropositive, whereas six (11 %) of 54 initially seropositive
      patients converted into seronegative. Our results might support the safety of
      long-term rituximab treatment in patients with NMOSD with regard to the risk of
      developing PML.

PMID- 25559685
TI  - Corrigendum.

PMID- 25559684
TI  - "Myo-cardiomyopathy" is commonly associated with the A8344G "MERRF" mutation.
AB  - The objective of the study was to better characterize the clinical phenotype
      associated with the A8344G "MERRF" mutation of mitochondrial DNA. Fifteen mutated
      patients were extensively investigated. The frequency of main clinical features
      was: exercise intolerance and/or muscle weakness 67 %, respiratory involvement 67
      %, lactic acidosis 67 %, cardiac abnormalities 53 %, peripheral neuropathy 47 %,
      myoclonus 40 %, epilepsy 40 %, ataxia 13 %. A restrictive respiratory
      insufficiency requiring ventilatory support was observed in about half of our
      patients. One patient developed a severe and rapidly progressive cardiomyopathy
      requiring cardioverter-defibrillator implantation. Five patients died of
      overwhelming, intractable lactic acidosis. Serial muscle MRIs identified a
      consistent pattern of muscle involvement and progression. Cardiac MRI showed non
      ischemic late gadolinium enhancement in the left ventricle inferolateral part as
      early sign of myocardial involvement. Brain spectroscopy demonstrated increased
      peak of choline and reduction of N-acetylaspartate. Lactate was never detected in
      brain areas, while it could be documented in ventricles. We confirm that muscle
      involvement is the most frequent clinical feature associated with A8443G
      mutation. In contrast with previous reports, however, about half of our patients
      did not develop signs of CNS involvement even in later stages of the disease. The
      difference may be related to the infrequent investigation of A8344G mutation in
      'pure' mitochondrial myo-cardiomyopathy, representing a bias and a possible cause
      of syndrome's underestimation. Our study highlights the importance of lactic
      acidosis and respiratory muscle insufficiency as critical prognostic factors.
      Muscle and cardiac MRI and brain spectroscopy may be useful tools in diagnosis
      and follow-up of MERRF. 

PMID- 25559686
TI  - Examining perceived cancer risk among patients with neurofibromatosis type 1.
AB  - Neurofibromatosis 1 (NF1) is a genetic disorder in which patients are at
      significantly increased risk for developing malignant peripheral nerve sheath
      tumors (MPNST) and malignant gliomas (brain cancer). We sought to develop a
      measure for assessing perceived risk of developing MPNST and brain cancer among
      patients with NF1 and to examine patients' perceived risk of developing these
      cancers. We assessed 112 NF1 patients' perceived risk of developing MPNST and
      brain cancer using an 8-item scale we developed that yielded two subscales in a
      principal component analysis (PCA). Linear regression models examined factors
      associated with perceived risk of malignancy. 33.9 % and 47.3 % of patients
      disagreed that having NF1 placed them at increased risk for MPNST and brain
      cancer, respectively. The PCA of the perceived risk items yielded a 2-factor
      solution with an MPNST and a brain subscale (total scale alpha = 0.90). Level of
      anxiety was the primary factor associated with perceived risk for both cancers. A
      significant proportion of NF1 patients underestimate their risk of developing
      MPNST and brain cancer. Perceived risk was associated with emotional distress, in
      particular anxiety. Clinicians should actively communicate with NF1 patients
      about their elevated cancer risk.

PMID- 25559687
TI  - Characterizing the peritumoral brain zone in glioblastoma: a multidisciplinary
      analysis.
AB  - Glioblastoma (GB) is the most frequent and aggressive type of primary brain
      tumor. Recurrences are mostly located at the margin of the resection cavity in
      the peritumoral brain zone (PBZ). Although it is widely believed that
      infiltrative tumor cells in this zone are responsible for GB recurrence, few
      studies have examined this zone. In this study, we analyzed PBZ left after
      surgery with a variety of techniques including radiology, histopathology, flow
      cytometry, genomic, transcriptomic, proteomic, and primary cell cultures. The
      resulting PBZ profiles were compared with those of the GB tumor zone and normal
      brain samples to identify characteristics specific to the PBZ. We found that
      tumor cell infiltration detected by standard histological analysis was present in
      almost one third of PBZ taken from an area that was considered normal both on
      standard MRI and by the neurosurgeon under an operating microscope. The panel of
      techniques used in this study show that the PBZ, similar to the tumor zone
      itself, is characterized by substantial inter-patient heterogeneity, which makes
      it difficult to identify representative markers. Nevertheless, we identified
      specific alterations in the PBZ such as the presence of selected tumor clones and
      stromal cells with tumorigenic and angiogenic properties. The study of GB-PBZ is
      a growing field of interest and this region needs to be characterized further.
      This will facilitate the development of new, targeted therapies for patients with
      GB and the development of approaches to refine the per-operative evaluation of
      the PBZ to optimize the surgical resection of the tumor. 

PMID- 25559688
TI  - Predicting early brain metastases based on clinicopathological factors and gene
      expression analysis in advanced HER2-positive breast cancer patients.
AB  - The overexpression or amplification of the human epidermal growth factor receptor
      2 gene (HER2/neu) is associated with high risk of brain metastasis (BM). The
      identification of patients at highest immediate risk of BM could optimize
      screening and facilitate interventional trials. We performed gene expression
      analysis using complementary deoxyribonucleic acid-mediated annealing, selection,
      extension and ligation and real-time quantitative reverse transcription PCR (qRT
      PCR) in primary tumor samples from two independent cohorts of advanced HER2
      positive breast cancer patients. Additionally, we analyzed predictive relevance
      of clinicopathological factors in this series. Study group included discovery
      Cohort A (84 patients) and validation Cohort B (75 patients). The only
      independent variables associated with the development of early BM in both cohorts
      were the visceral location of first distant relapse [Cohort A: hazard ratio (HR)
      7.4, 95 % CI 2.4-22.3; p < 0.001; Cohort B: HR 6.1, 95 % CI 1.5-25.6; p = 0.01]
      and the lack of trastuzumab administration in the metastatic setting (Cohort A:
      HR 5.0, 95 % CI 1.4-10.0; p = 0.009; Cohort B: HR 10.0, 95 % CI 2.0-100.0; p =
      0.008). A profile including 13 genes was associated with early (<=36 months)
      symptomatic BM in the discovery cohort. This was refined by qRT-PCR to a 3-gene
      classifier (RAD51, HDGF, TPR) highly predictive of early BM (HR 5.3, 95 % CI 1.6
      16.7; p = 0.005; multivariate analysis). However, predictive value of the
      classifier was not confirmed in the independent validation Cohort B. The presence
      of visceral metastases and the lack of trastuzumab administration in the
      metastatic setting apparently increase the likelihood of early BM in advanced
      HER2-positive breast cancer.

PMID- 25559689
TI  - Grading glial tumors with amide proton transfer MR imaging: different analytical
      approaches.
AB  - Amide proton transfer (APT) magnetic resonance imaging is gaining attention for
      its capability for grading glial tumors. Usually, a representative slice is
      analyzed. Different definitions of tumor areas have been employed in previous
      studies. We hypothesized that the accuracy of APT imaging for brain tumor grading
      may depend upon the analytical methodology used, such as selection of regions of
      interest (ROIs), single or multiple tumor slices, and whether or not there is
      normalization to the contralateral white matter. This study was approved by the
      institutional review board, and written informed consent was waived. Twenty-six
      patients with histologically proven glial tumors underwent preoperative APT
      imaging with a three-dimensional gradient-echo sequence. Two neuroradiologists
      independently analyzed APT asymmetry (APTasym) images by placing ROIs on both a
      single representative slice (RS) and all slices including tumor (i.e. whole
      tumor: WT). ROIs indicating tumor extent were separately defined on both FLAIR
      and, if applicable, contrast-enhanced T1-weighted images (CE-T1WI), yielding four
      mean APTasym values (RS-FLAIR, WT-FLAIR, RS-CE-T1WI, and WT-CE-T1WI). The maximum
      values were also measured using small ROIs, and their differences among grades
      were evaluated. Receiver operating characteristic (ROC) curve analysis was also
      conducted on mean and maximum values. Intra-class correlation coefficients for
      inter-observer agreement were excellent. Significant differences were observed
      between high- and low-grade gliomas for all five methods (P < 0.01). ROC curve
      analysis found no statistically significant difference among them. This study
      clarifies that single-slice APT analysis is robust despite tumor heterogeneity,
      and can grade glial tumors with or without the use of contrast material.

PMID- 25559690
TI  - New steroidal glycosides from Hosta plantaginea (Lam.) Aschers.
AB  - Four new furostanol glycosides were isolated from the flowers of Hosta
      plantaginea (Lam.) Aschers. On the basis of spectroscopic methods including 1D
      and 2D NMR experiments, their structures were elucidated as 26-O-beta-d
      glucopyranosyl-(25R)-22-O-methyl-5alpha-furostan-2alpha,3beta,22xi,26-tetrol 3-O
      alpha-l-rhamnopyranosyl-(1 -> 4)-O-beta-d-xylopyranosyl-(1 -> 3)-[O-beta-d
      glucopyranosyl-(1 -> 2)]-O-beta-d-glucopyranosyl-(1 -> 4)-beta-d
      galactopyranoside (hostaplantagineoside A, 1), 26-O-beta-d-glucopyranosyl-(25R)
      5alpha-furostan-20(22)-ene-2alpha,3beta,26-triol-3-O-beta-d-glucopyranosyl-(1 ->
      2)-[O-beta-d-xylopyranosyl-(1 -> 3)]-O-beta-d-glucopyranosyl-(1 -> 4)-beta-d
      galactopyranoside (hostaplantagineoside B, 2), 26-O-beta-d-glucopyranosyl-(25R)
      5alpha-furostan-22(23)-ene-2alpha,3beta,20alpha,26-tetraol-3-O-beta-d
      glucopyranosyl-(1 -> 2)-[O-beta-d-xylopyranosyl-(1 -> 3)]-O-beta-d-glucopyranosyl
      (1 -> 4)-O-beta-d-galactopyranoside (hostaplantagineoside C, 3), 26-O-beta-d
      glucopyranosyl-(25R)-5alpha-furostan-20(22)-ene-2alpha,3beta,26-triol-3-O-alpha-l
      rhamnopyranosyl-(1 -> 4)-O-beta-d-xylopyranosyl-(1 -> 3)-[O-beta-d-glucopyranosyl
      (1 -> 2)]-O-beta-d-glucopyranosyl-(1 -> 4)-beta-d-galactopyranoside
      (hostaplantagineoside D, 4). 

PMID- 25559691
TI  - Health-related quality of life after allogeneic hematopoietic stem cell
      transplantation for sickle cell disease.
AB  - Sickle cell disease (SCD) is a hereditary hemoglobinopathy that affects over
      100,000 people in the United States. Patients with SCD are known to experience
      suboptimal health-related quality of life (HRQoL). In addition to the physical
      manifestations of SCD, psychological and social stress, along with academic
      difficulties, secondary to the chronicity of the disease and its complications
      often affect patients with SCD. Although medical therapy of SCD has improved,
      allogeneic hematopoietic cell transplantation (allo-HCT) remains the only
      curative therapy. The objective of this study was to measure HRQoL before and
      after allo-HCT by assessing physical, psychological, and social functioning in
      patients with SCD who have undergone reduced-toxicity conditioning
      (busulfan/fludarabine/alemtuzumab) followed by allo-HCT. Patients < 21 years of
      age undergoing allo-HCT (matched siblings and unrelated donors) for SCD and their
      primary caregiver were enrolled using either the English or Spanish version of
      the PedsQoL 4.0. Data were collected at 3 time points: before allo-HCT and on
      days 180 and 365 after allo-HCT. The change in HRQoL from baseline was assessed
      with unadjusted and adjusted mixed-effects models in which subjects were treated
      as random effects, and variance component structure was used. Seventeen patients
      and 23 primary caregivers were enrolled and reported a mean overall HRQoL of
      66.05 (SD, 15.62) and 72.20 (SD, 15.50) at baseline, respectively. In the patient
      reported analysis with adjusted mixed-effects models, the estimated improvements
      in overall HRQoL were 4.45 (SE, 4.98; P = .380) and 16.58 (SE, 5.06; P = .003) at
      180 and 365 days, respectively, after allo-HCT. For parent-reported overall
      HRQoL, the estimated improvements were 1.57 (SE, 4.82; P = .747) and 9.28 (SE,
      4.62; P = .053) at 180 and 365 days, respectively, after allo-HCT. Similar
      results were found across the physical, social, and emotional HRQoL domains with
      mixed-effects models after adjustment of demographic and medical variables. In
      addition to the alleviation of clinical manifestations of SCD, these patients
      demonstrated significant improvement in most aspects of HRQoL by 1 year after
      allo-HCT. These data represent the trajectory of HRQoL during the initial year of
      follow-up within this population and should be integrated into the decision
      making process when considering allo-HCT in patients with SCD.

PMID- 25559692
TI  - Quantitative assessment of the effect of cholesterol on blood glucose measurement
      using near infrared spectroscopy and a method for error reduction.
AB  - BACKGROUND AND OBJECTIVE: There is a growing body of evidence suggesting that the
      accurate measurement of blood glucose concentration can be perturbed by many
      factors. Current literature is limited in describing the influence of cholesterol
      on non-invasive blood glucose measurements by near-infrared spectroscopy (NIRS).
      This study aims to investigate the influence of cholesterol on blood glucose
      measurement through clinical oral glucose tolerance test (OGTT) and NIRS.
      Further, a method to reduce the prediction errors induced by cholesterol is
      proposed, facilitating the clinical application of non-invasive blood glucose
      sensing by NIRS. STUDY DESIGN/MATERIAL AND METHODS: We obtained clinical data of
      glucose and cholesterol concentrations at specific time points (0, 0.5, 1, 2, and
      3 h) during OGTTs from 115 subjects. The subjects were grouped into: Norm for
      normal control, IGT for Impaired Glucose Tolerance, and Diabetes. In addition,
      spectral data between 1200 and 1800 nm were collected from 130 phantom samples,
      which are separated into seven groups depending on glucose and cholesterol
      levels. Statistical methods including One Sample T-test (OSTT), Pearson
      Correlation Analysis(PCA), and Unary Linear Regression (ULR) were used to analyze
      clinical data and spectral data to determine the relationship between glucose and
      cholesterol concentrations with the time course of OGTT. Reference wavelength
      based method (RWM) was introduced to diminish the influence of cholesterol on
      glucose measurement and further the prediction error induced by cholesterol was
      reduced when using partial least square (PLS) model. RESULTS: Clinical results
      statistically show that there is a strong negative correlation between the
      changes of glucose and cholesterol concentrations in the diabetes group. The
      spectra of cholesterol exhibit similar absorbance peaks to those of glucose
      within NIR range. PLS modelling results demonstrate that glucose prediction is
      influenced by cholesterol concentrations in a calibration model. Furthermore, a
      model expression (DeltaCg=0.0356Cc+1.0129 R(2)  = 0.993) is fitted to
      quantitatively describe the glucose prediction increment (DeltaCg) due to
      cholesterol concentration (Cc). The results show that glucose prediction accuracy
      can be improved up to 38.36% by using RWM when using NIRS. CONCLUSIONS: The
      cholesterol has an effect on blood glucose sensing. RWM is useful to help realize
      non-invasive blood glucose sensing by NIRS.

PMID- 25559693
TI  - Platform switch and dental implants: A meta-analysis.
AB  - OBJECTIVES: To test the null hypothesis of no difference in the implant failure
      rates, marginal bone loss (MBL) and postoperative infection in patients who
      received platform-switched implants or platform-matched implants, against the
      alternative hypothesis of a difference. DATA: Main search terms used in
      combination: dental implant, oral implant, platform switch, switched platform,
      platform mismatch, and dental implant-abutment design. SOURCES: An electronic
      search without time or language restrictions was undertaken in December/2014 in
      PubMed/Medline, Web of Science, Cochrane Oral Health Group Trials Register plus
      hand-searching. STUDY SELECTION: Eligibility criteria included clinical human
      studies, either randomized or not. CONCLUSIONS: Twenty-eight publications were
      included, with a total of 1216 platform-switched implants (16 failures; 1.32%)
      and 1157 platform-matched implants (13 failures; 1.12%). There was less MBL loss
      at implants with platform-switching than at implants with platform-matching (mean
      difference -0.29, 95% CI -0.38 to -0.19; P<0.00001). An increase of the mean
      difference of MBL between the procedures was observed with the increase in the
      follow-up time (P=0.001) and with the increase of the mismatch between the
      implant platform and the abutment (P=0.001). Due to lack of satisfactory
      information, meta-analyses for the outcomes 'implant failure' and 'postoperative
      infection' were not performed. The results of the present review should be
      interpreted with caution due to the presence of uncontrolled confounding factors
      in the included studies, most of them with short follow-up periods. CLINICAL
      SIGNIFICANCE: The question whether platform-matched implants are more at risk for
      failure and loose more marginal bone than platform-switched implants has received
      increasing attention in the last years. As the philosophies of treatment alter
      over time, a periodic review of the different concepts is necessary to refine
      techniques and eliminate unnecessary procedures, forming a basis for optimum
      treatment.

PMID- 25559694
TI  - The Effect of Kinesio Taping on Muscle Pain, Sprint Performance, and Flexibility
      in Recovery From Squat Exercise in Young Adult Women.
AB  - CONTEXT: Kinesio taping (KT) is a taping technique extensively used in
      rehabilitation of sports injuries; however, the effect of KT on delayed-onset
      muscle soreness is not entirely clear. OBJECTIVES: To investigate the effect of
      kinesio tape on the quadriceps femoris on muscle pain, flexibility, and sprint
      performance after squat exercise. DESIGN: Crossover study. SETTING: University
      research laboratory. PARTICIPANTS: 19 female university students (age 21.0 +/-
      1.2 y, weight 53.0 +/- 4.6 kg, height 164 +/- 4 cm). MAIN OUTCOME MEASURES:
      Pressure-pain threshold for quadriceps femoris was recorded using pressure
      algometry. Quadriceps femoris flexibility was measured as the range of motion of
      knee flexion with a stainless steel goniometer. Sprint-speed measurements were
      conducted using photocells placed at 0 and 20 m. All participants completed both
      conditions (KT application and no KT application) after a 1-wk washout period.
      Measurements were taken at baseline and 48 h postexercise. For the KT condition,
      KT was applied immediately before the exercise protocol and remained on the skin
      for 48 h. RESULTS: Squat exercise reduced flexibility and increased pain and
      sprint time compared with baseline. KT application resulted in similar sprint
      time and muscle pain as the no-KT condition but maintained flexibility compared
      with baseline. CONCLUSIONS: KT application immediately before squat exercise has
      no effect on muscle pain and short sprint performance but maintains muscle
      flexibility at 2 days of recovery.

PMID- 25559695
TI  - An unprecedented 3D POM-MOF based on (7,8)-connected twin Wells-Dawson clusters:
      synthesis, structure, electrocatalytic and photocatalytic properties.
AB  - The first (7,8)-connected polyoxometalate-based metal-organic framework (POM-MOF)
      has been constructed from seven- and eight-connected twin Wells-Dawson clusters,
      and possesses the highest connection number of polyoxometalates to any mixed
      connected POM-MOF to date and a unique structural motif that contains both
      organic-inorganic and all-inorganic networks. 

PMID- 25559696
TI  - Expansion dynamics of supercritical water probed by picosecond time-resolved
      photoelectron spectroscopy.
AB  - Vibrational excitation of liquid water with femtosecond laser pulses can create
      extreme states of water. Yet, the dynamics directly after initial sub-picosecond
      delocalization of molecular vibrations remain largely unclear. We study the
      ultrafast expansion dynamics of an accordingly prepared supercritical water phase
      with a picosecond time resolution. Our experimental setup combines vacuum
      compatible liquid micro-jet technology and a table top High Harmonic light source
      driven by a femtosecond laser system. An ultrashort laser pulse centered at a
      wavelength of 2900 nm excites the OH-stretch vibration of water molecules in the
      liquid. The deposited energy corresponds to a supercritical phase with a
      temperature of about 1000 K and a pressure of more than 1 GPa. We use a time
      delayed extreme ultraviolet pulse centered at 38.6 eV, and obtained via High
      Harmonic generation (HHG), to record valence band photoelectron spectra of the
      expanding water sample. The series of photoelectron spectra is analyzed with
      noise-corrected target transform fitting (cTTF), a specifically developed
      multivariate method. Together with a simple fluid dynamics simulation, the
      following picture emerges: when a supercritical phase of water expands into
      vacuum, temperature and density of the first few nanometers of the expanding
      phase drop below the critical values within a few picoseconds. This results in a
      supersaturated phase, in which condensation seeds form and grow from small
      clusters to large clusters on a 100 picosecond timescale. 

PMID- 25559698
TI  - "Disease" of the nation, family and individual: three moral discourses of alcohol
      problems in Finnish women's magazines from the 1960s to the 2000s.
AB  - Women's magazines can be seen as a genre that form feminized public spaces where
      everyday life contradictions of women's life are negotiated. The study examines
      the ways in which Finnish women's magazines have dealt with alcohol problems. The
      data covers six primary sampling years: 1968, 1976, 1984, 1992, 2000 and 2008.
      The data is analyzed by drawing on the concept of 'moral regulation'. The
      analysis shows that a family-centered framing dominated the constructions of
      alcohol problem: fathers' and husbands' alcoholism appeared as a main object of
      regulation in all decades under study, while mothers' and wives' alcoholism was
      much less prevalent. 

PMID- 25559697
TI  - Determining Smoking Cessation Related Information, Motivation, and Behavioral
      Skills among Opiate Dependent Smokers in Methadone Treatment.
AB  - BACKGROUND: Over 80% of people in methadone treatment smoke cigarettes, and
      existing smoking cessation interventions have been minimally effective.
      OBJECTIVE: To develop an Information-Motivation-Behavioral Skills (IMB) Model of
      behavior change based smoking cessation intervention for methadone maintained
      smokers, we examined smoking cessation related IMB factors in this population.
      METHODS: Current or former smokers in methadone treatment (n = 35) participated
      in focus groups. Ten methadone clinic counselors participated in an individual
      interview. A content analysis was conducted using deductive and inductive
      approaches. RESULTS: Commonly known IMB factors related to smoking cessation were
      described. These factors included: the health effects of smoking and treatment
      options for quitting (information); pregnancy and cost of cigarettes
      (motivators); and coping with emotions, finding social support, and
      pharmacotherapy adherence (behavioral skills). IMB factors specific to methadone
      maintained smokers were also described. These factors included: the relationship
      between quitting smoking and drug relapse (information), the belief that smoking
      is the same as using drugs (motivator); and coping with methadone clinic culture
      and applying skills used to quit drugs to quitting smoking (behavioral skills).
      IMB strengths and deficits varied by individual. CONCLUSIONS: Methadone
      maintained smokers could benefit from research on an IMB Model based smoking
      cessation intervention that is individualized, addresses IMB factors common among
      all smokers, and also addresses IMB factors unique to this population.

PMID- 25559699
TI  - Images by the vineyard: images of addiction and substance users in the media and
      other culture sites/sights.
AB  - This article constitutes a discovery journey into the world of drinking images,
      the pleasures and harms related to consuming alcoholic beverages, as well as the
      relationships between drinking and spirituality. These aspects are described
      historically and globally, over time through a series of snapshots and mini
      discussions about both visual and mental images from art, classical literature
      and operatic music.The images are interpreted according to how they represent the
      drinking culture within which they were created and sustained, and how they are
      able to involve the spectator and the user in terms of either empathizing,
      accepting and including or distancing, stigmatizing and marginalizing the user. 

PMID- 25559700
TI  - The chemistry of xenon(IV).

PMID- 25559701
TI  - Plant protection product residues in red grapes and Teran PTP wine.
AB  - Between 2011 and 2013, a total of 73 grape and 82 wine samples from winegrowing
      district Kras (Karst) were analysed for plant protection product (PPP) residues.
      The samples were analysed for the presence of 215 different active compounds
      using two multiresidual analytical methods: gas chromatography coupled with mass
      spectrometry and liquid chromatography coupled with tandem mass spectrometry.
      Residues were found in 91.8% of all grape samples and in 67.1% of all wine
      samples. In all grape samples, residues were below maximum residue levels (MRLs)
      and 58.9% of all grape samples contained active substances at a level of less
      then 10% of the MRL. Nearly 33% of all Teran PTP wines did not contain PPP
      residues at all. Residues diminish during processing of grapes to wine, so their
      content in wine was low. Therefore, it could be concluded that grapes and wine in
      the winegrowing district Kras are safe for consumers. 

PMID- 25559702
TI  - [Keratitis in an elderly patient].

PMID- 25559703
TI  - Mucocutaneous leishmaniasis caused by Leishmania infantum var Lombardi in an
      immunocompetent patient, Spain.

PMID- 25559704
TI  - [Chronic pain and a single lesion in the distal radius].

PMID- 25559705
TI  - [Rapid antibiotic susceptibility test in Clinical Microbiology].
AB  - The most widely used antibiotic susceptibility testing methods in Clinical
      Microbiology are based on the phenotypic detection of antibiotic resistance by
      measuring bacterial growth in the presence of the antibiotic being tested. These
      conventional methods take typically 24hours to obtain results. A review is
      presented here of recently developed techniques for the rapid determination of
      antibiotic susceptibility. Data obtained with different methods such as molecular
      techniques, flow cytometry, chemiluminescence, mass spectrometry, commercial
      methods used in routine work, colorimetric methods, nephelometry, microarrays,
      microfluids, and methods based on cell disruption and sequencing, are analyzed
      and discussed in detail. 

PMID- 25559706
TI  - Racial athletic stereotype confirmation in college football recruiting.
AB  - The present study tested real-world racial stereotype use in the context of
      college athletic recruiting. Stereotype confirmation suggests that observers use
      stereotypes as hypotheses and interpret relevant evidence in a biased way that
      confirms their stereotypes. Shifting standards suggest that the evaluative
      standard to which we hold a target changes as a function of their group
      membership. We examined whether stereotype confirmation and shifting standards
      effects would be seen in college football coaches during recruiting. College
      football coaches evaluated a Black or White player on several attributes and made
      both zero- and non-zero-sum allocations. Results suggested that coaches used the
      evidence presented to develop biased subjective evaluations of the players based
      on race while still maintaining equivalent objective evaluations. Coaches also
      allocated greater overall resources to the Black recruit than the White recruit. 

PMID- 25559707
TI  - First-principles calculations of oxygen vacancy formation and metallic behavior
      at a beta-MnO2 grain boundary.
AB  - Nanostructured MnO2 is renowned for its excellent energy storage capability and
      high catalytic activity. While the electronic and structural properties of MnO2
      surfaces have received significant attention, the properties of the grain
      boundaries (GBs) and their contribution to the electrochemical performance of the
      material remains unknown. Through density functional theory (DFT) calculations,
      the structure and electronic properties of the beta-MnO2 Sigma 5(210)/[001] GB
      are studied. Our calculations show this low energy GB has a significantly reduced
      band gap compared to the pristine material and that the formation of oxygen
      vacancies produces spin-polarized states that further reduce the band gap.
      Calculated formation energies of oxygen vacancy defects and Mn reduction at the
      GB core are all lower than the equivalent bulk value and in some cases lower than
      values recently calculated for beta-MnO2 surfaces. Oxygen vacancy formation is
      also shown to produce a metallic behavior at the GB with defect charge
      distributed over a number of oxygen and manganese sites. The low energies of
      oxygen defect formation and the potential creation of conductive GB pathways are
      likely to be important to the electrochemical performance of beta-MnO2. 

PMID- 25559709
TI  - Brief online surveys to monitor and evaluate facilitated peer support groups for
      caregivers of children with special needs.
AB  - BACKGROUND: There have been few systematic evaluations of experiences of
      participating in peer support groups for parents and other caregivers of children
      with special needs. In Australia, facilitated groups are available to caregivers
      in community settings, through a nationally funded program, MyTime. Mechanisms
      for ongoing monitoring and evaluation have not yet been instituted. AIM: To
      establish whether brief, online surveys can be used for monitoring and evaluating
      peer support groups for caregivers of children with special needs. METHODS: Two
      brief, online surveys, with both fixed-choice and open-ended questions, were
      developed. All caregivers who attended any MyTime group during a 1-month period
      were invited to participate. RESULTS: Of 89 caregivers who expressed interest in
      participating, 54 and 31 respondents completed respectively. Respondents
      represented a variety of backgrounds and circumstances. Responses revealed both
      positive and negative aspects of group participation. Linked data on expectations
      and experiences provided important feedback for the program. CONCLUSION: Brief,
      online surveys are a suitable mechanism for ongoing monitoring and evaluation of
      peer support group programs for caregivers.

PMID- 25559708
TI  - Adipose tissue derived stem cells: in vitro and in vivo analysis of a standard
      and three commercially available cell-assisted lipotransfer techniques.
AB  - INTRODUCTION: Autologous fat grafting is commonly used to correct soft-tissue
      contour deformities. However, results are impaired by a variable and
      unpredictable resorption rate. Autologous adipose-derived stromal cells in
      combination with lipoinjection (cell-assisted lipotransfer) seem to favor a long
      term persistence of fat grafts, thus fostering the development of devices to be
      used in the operating room at the point of care, to isolate the stromal vascular
      fraction (SVF) and produce SVF-enhanced fat grafts with safe and standardized
      protocols. Focusing on patients undergoing breast reconstruction by
      lipostructure, we analyzed a standard technique, a modification of the Coleman's
      procedure, and three different commercially available devices (Lipokit, Cytori,
      Fastem), in terms of 1) ability to enrich fat grafts in stem cells and 2)
      clinical outcome at 6 and 12 months. METHODS: To evaluate the ability to enrich
      stem cells, we compared, for each patient (n=20), the standard lipoaspirate with
      the respective stem cell-enriched one, analyzing yield, immunophenotype and
      colony-forming capacity of the SVF cells as well as immunophenotype,
      clonogenicity and multipotency of the obtained adipose stem cells (ASCs).
      Regarding the clinical outcome, we compared, by ultrasonography imaging, changes
      at 6 and 12 months in the subcutaneous thickness of patients treated with stem
      cell enriched (n=14) and standard lipoaspirates (n=16). RESULTS: Both methods
      relying on the enzymatic isolation of primitive cells led to significant increase
      in the frequency, in the fat grafts, of SVF cells as well as of clonogenic and
      multipotent ASCs, while the enrichment was less prominent for the device based on
      the mechanical isolation of the SVF. From a clinical point of view, patients
      treated with SVF-enhanced fat grafts demonstrated, at six months, a significant
      superior gain of thickness of both the central and superior-medial quadrants with
      respect to patients treated with standard lipotransfer. In the median-median
      quadrant the effect was still persistent at 12 months, confirming an advantage of
      lipotransfer technique in enriching improving long-term fat grafts. CONCLUSIONS:
      This comparative study, based on reproducible biological and clinical parameters
      and endpoints, showed an advantage of lipotransfer technique in enriching fat
      grafts in stem cells and in favoring, clinically, long-term fat grafts.

PMID- 25559710
TI  - The bacterial pneumonias: a new treatment paradigm.
AB  - Pneumonia is a common disease that carries a high mortality. Traditionally,
      pneumonia has been classified and treated according to the setting where the
      pneumonia develops, namely community-acquired pneumonia, health-care-associated
      pneumonia, and hospital-acquired pneumonia. This classification was based on the
      risk of a patient being infected with a hospital-acquired drug-resistant
      pathogen. A new treatment paradigm has been proposed based on the risk of the
      patient being infected with a community-acquired drug-resistant pathogen. The
      risk factors for infection with a community-acquired drug-resistant pathogen
      include (1) hospitalization for > 2 days during the previous 90 days, (2)
      antibiotic use during the previous 90 days, (3) nonambulatory status, (4) tube
      feeds, (5) immunocompromised status, (6) use of acid-suppressive therapy, (7)
      chronic hemodialysis during the preceding 30 days, (8) positive methicillin
      resistant Staphylococcus aureus history within the previous 90 days, and (9)
      present hospitalization > 2 days. This article reviews this new treatment
      paradigm and other issues relevant to the diagnosis and management of pneumonia
      based on information from MEDLINE, EMBASE, and the Cochrane Register of
      Controlled Trials.

PMID- 25559711
TI  - Nanoscale nuclear magnetic imaging with chemical contrast.
AB  - Scanning probe microscopy is one of the most versatile windows into the
      nanoworld, providing imaging access to a variety of electronic, dielectric,
      magnetic and topographic sample properties, depending on the probe used. Here, we
      demonstrate a scanning probe imaging method that extends the range of accessible
      quantities to label-free imaging of chemical species while operating on arbitrary
      samples--including insulating materials--under ambient conditions. Moreover, its
      sensitivity extends below the surface of a sample, allowing for imaging of
      subsurface features. We achieve these results by recording NMR signals from a
      sample surface with a recently introduced scanning probe, a single nitrogen
      vacancy centre in diamond. We demonstrate NMR imaging with 10 nm resolution and
      achieve chemically specific contrast by separating fluorine from hydrogen-rich
      regions. Our result opens the door to scanning probe imaging of the chemical
      composition and molecular structure of arbitrary samples. A method with these
      abilities will find widespread application in materials science, even on
      biological specimens down to the level of single macromolecules.

PMID- 25559713
TI  - Emotional complexity and its effect on psychological distress as a function of
      chronological age and subjective distance-to-death.
AB  - OBJECTIVES: In light of mixed evidence regarding the associations between age,
      emotional complexity, and psychological distress, this study examined emotional
      complexity and its effect on psychological distress as a function of age and
      subjective distance-to-death. METHOD: A sample of 188 participants (age range =
      29-100) rated their subjective distance-to-death and psychological distress, and
      reported their emotions across 14 days. RESULTS: Emotional complexity was
      unrelated to age, but negatively related to feeling closer to death. Moreover,
      emotional complexity was negatively related to psychological distress among those
      feeling closer to death. CONCLUSION: Results suggest that when death is perceived
      to be nearer, emotional complexity is hampered, yet becomes relevant in buffering
      psychological distress.

PMID- 25559712
TI  - Nanoscale NMR spectroscopy and imaging of multiple nuclear species.
AB  - Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging
      (MRI) provide non-invasive information about multiple nuclear species in bulk
      matter, with wide-ranging applications from basic physics and chemistry to
      biomedical imaging. However, the spatial resolution of conventional NMR and MRI
      is limited to several micrometres even at large magnetic fields (>1 T), which is
      inadequate for many frontier scientific applications such as single-molecule NMR
      spectroscopy and in vivo MRI of individual biological cells. A promising approach
      for nanoscale NMR and MRI exploits optical measurements of nitrogen-vacancy (NV)
      colour centres in diamond, which provide a combination of magnetic field
      sensitivity and nanoscale spatial resolution unmatched by any existing
      technology, while operating under ambient conditions in a robust, solid-state
      system. Recently, single, shallow NV centres were used to demonstrate NMR of
      nanoscale ensembles of proton spins, consisting of a statistical polarization
      equivalent to ~100-1,000 spins in uniform samples covering the surface of a bulk
      diamond chip. Here, we realize nanoscale NMR spectroscopy and MRI of multiple
      nuclear species ((1)H, (19)F, (31)P) in non-uniform (spatially structured)
      samples under ambient conditions and at moderate magnetic fields (~20 mT) using
      two complementary sensor modalities. 

PMID- 25559714
TI  - Acromegaly due to a Macroinvasive Plurihormonal Pituitary Adenoma and a Rectal
      Carcinoid Tumor.
AB  - A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly
      and hyperprolactinemia, and also accompanies with neurologic symptoms such as
      visual disturbances. However, its concurrent presentation with a rectal carcinoid
      tumor is rarely observed. This study reports the history, biochemical,
      colonoscopic and immunohistochemical results of a 48-year-old female with
      acromegaly and hyperprolactinemia. Despite the large size and invasive nature of
      the pituitary adenoma to adjacent anatomical structures, she did not complain of
      any neurologic symptoms such as visual disturbance or headache.
      Immunohistochemical staining of the surgical specimen from the pituitary adenoma
      revealed that the tumor cells were positive for growth hormone (GH), prolactin
      (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific
      transcription factor-1 (Pit-1) was shown to be strongly positive, which could
      have been possibly contributing to the plurihormonality of this adenoma.
      Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor
      using immunohistochemical staining. A macroinvasive pituitary adenoma with
      concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were
      believed to be in association with over-expression of Pit-1. This is the first
      case report of double primary tumors comprising a plurihormonal pituitary
      macroadenoma and rectal carcinoid tumor. 

PMID- 25559715
TI  - Physiological Parameters in the Blood of a Murine Stress-Induced Depression Model
      before and after Repeated Passive Exercise.
AB  - BACKGROUND: Animal models are necessary to study the mechanism underlying the
      effects of exercise on depression but an effective procedure for exercise
      treatment and exercise effects on physiological parameters in a specific
      depression model need to be characterized. METHODS: Physiological parameters
      including lactate, partial pressue of O2 (pO2) and CO2 (pCO2) saturated O2 (sO2),
      pH, HCO3, total CO2 (TCO2), and base excess extracellular fluid (BEecf) levels in
      the blood were measured after treatment with passive exercise in normal mice and
      a stress-induced depression model. RESULTS: Normal mice or mice that were
      subjected to daily 2-hour restraint for 14 days (2 hours * 14 days of restraint)
      were placed on a running wheel that was rotating at a speed of 9 m/min for 1 hour
      per day for 1 to 21 days. After repeated exercise in mice that were previously
      subjected to 2 hours * 14 days restraint, plasma lactate levels decreased, the
      levels of pO2, sO2, and pH tended to increase, and the levels of pCO2 decreased
      in the absence of significant changes in HCO3, TCO2, and BEecf. However, none of
      these changes were additive to the stress effects or were much more severe than
      those induced after repeated passive exercise in normal mice. CONCLUSION: These
      results suggest that passive exercise for 1 hour daily for 14 to 21 consecutive
      days on a running wheel rotating at a speed of 9 m/min may be used as an exercise
      protocol without inducing severe additive effects on physiological burdens.

PMID- 25559717
TI  - Incidence and Prevalence of Overt Hypothyroidism and Causative Diseases in Korea
      as Determined Using Claims Data Provided by the Health Insurance Review and
      Assessment Service.
AB  - BACKGROUND: The incidence and prevalence of overt hypothyroidism have been
      reported to be 2 to 4/1,000 population/year and 8 to 13/1,000 population,
      respectively, in foreign countries. As there has been no nationwide survey to
      obtain data in Korea, the present study investigated the incidence and prevalence
      of overt hypothyroidism in Korea using claims data provided by the Health
      Insurance Review and Assessment Service. The proportions of causative diseases
      for hypothyroidism were also analyzed. METHODS: This study was retrospectively
      performed with 541,969 Korean patients (92,832 men and 449,137 women), with overt
      hypothyroidism, treated with thyroid hormone between 2008 and 2012. RESULTS: The
      incidence of overt hypothyroidism in Korea was 2.26/1,000 population/year (0.78
      in men and 3.72 in women), and the prevalence was 14.28/1,000 population (4.40 in
      men and 24.03 in women). When patients with thyroid cancer were excluded, the
      incidence was 1.56/1,000 population/year (0.54 in men and 2.57 in women). The
      incidence increased with age, with peaks in and after the late 60s in men and in
      the early 50s in women. The prevalence peaked in the early 70s in men and in the
      late 50s in women. CONCLUSION: This is a report of the first nationwide
      investigation of the incidence and prevalence of overt hypothyroidism in Korea,
      although it is limited to patients treated with thyroid hormone.

PMID- 25559716
TI  - Association between the Growth Hormone Receptor Exon 3 Polymorphism and Metabolic
      Factors in Korean Patients with Acromegaly.
AB  - BACKGROUND: This study investigated the association between the frequency of
      growth hormone receptor (GHR) exon 3 polymorphism (exon 3 deletion; d3-GHR) and
      metabolic factors in patients with acromegaly in Korea. METHODS: DNA was
      extracted from the peripheral blood of 30 unrelated patients with acromegaly. GHR
      genotypes were evaluated by polymerase chain reaction and correlated with
      demographic data and laboratory parameters. RESULTS: No patient had the d3/d3
      genotype, while four (13.3%) had the d3/fl genotype, and 26 (86.7%) had the fl/fl
      genotype. Body mass index (BMI) in patients with the d3/fl genotype was
      significantly higher than in those with the fl/fl genotype (P=0.001). Age,
      gender, blood pressure, insulin-like growth factor-1, growth hormone, fasting
      plasma glucose, triglycerides, high density lipoprotein cholesterol, and low
      density lipoprotein cholesterol levels showed no significant differences between
      the two genotypes. CONCLUSION: The d3-GHR polymorphism may be associated with
      high BMI but not with other demographic characteristics or laboratory parameters.

PMID- 25559718
TI  - Enhancement of Short-Term Memory by Methyl-6-(Phenylethynyl)-Pyridine in the BTBR
      T+tf/J Mouse Model of Autism Spectrum Disorder.
AB  - BACKGROUND: Autism spectrum disorder (ASD) encompasses a range of disorders that
      are characterized by social and communication deficits and repetitive behaviors.
      This study evaluated the effect of methyl-6-(phenylethynyl)-pyridine (MPEP), an
      antagonist of the mGluR5 metabotropic glutamate receptor, on memory enhancement
      in the BTBR T+tf/J (BTBR) mouse strain, which has been recognized as a model of
      ASD. METHODS: The pharmacological effects of MPEP on memory and motor
      coordination were assessed using the Morris water maze and rotarod tests in BTBR
      and C57BL/6J (B6) mice. Furthermore, we performed morphological analyses of
      cerebellar foliation in BTBR and B6 mice using hematoxylin and eosin staining.
      RESULTS: MPEP-treated BTBR mice exhibited improved learning and memory in the
      Morris water maze test. MPEP administration also improved motor coordination in
      the rotarod test. However, no significant difference was observed regarding the
      numbers of Purkinje cells in the cerebella of BTBR versus normal B6 mice.
      CONCLUSION: This study suggests that the mGluR5 antagonist MPEP has the potential
      to ameliorate learning and memory dysfunction and impaired motor coordination in
      BTBR mice. These results further suggest that the BTBR mouse model may be useful
      in pharmacological studies investigating drugs that could potentially alleviate
      cognitive dysfunction in ASD.

PMID- 25559719
TI  - Predictive response surface model for heat-induced rheological changes and
      aggregation of whey protein concentrate.
AB  - Whey proteins are now far more than a by-product of cheese processing. In the
      last 2 decades, food manufacturers have developed them as ingredients, with the
      dairy industry remaining as a major user. For many applications, whey proteins
      are modified (denatured) to alter their structure and functional properties. The
      objective of this research was to study the influence of 85 to 100  degrees C,
      with protein concentration of 8% to 12%, and treatment times of 5 to 30 min,
      while measuring rheological properties (storage modulus, loss modulus, and
      complex viscosity) and aggregation (intermolecular beta-sheet formation) in
      dispersions of whey protein concentrate (WPC). A Box-Behnken Response Surface
      Methodology modeled the heat denaturation of liquid sweet WPC at 3 variables and
      3 levels. The model revealed a very significant fit for viscoelastic properties,
      and a lesser fit for protein aggregation, at temperatures not previously studied.
      An exponential increase of rheological parameters was governed by protein
      concentration and temperature, while a modest linear relationship of aggregation
      was governed by temperature. Models such as these can serve as valuable guides to
      the ingredient and dairy industries to develop target products, as whey is a
      major ingredient in many functional foods. 

PMID- 25559720
TI  - Thermo-chemical conversion of biomass.

PMID- 25559721
TI  - Advances in biogas research and application.

PMID- 25559723
TI  - Gross hematuria and focal renal masses as initial features of a mature B-cell
      leukemia in an adolescent male.
AB  - We report a case of a 14-year-old boy who presented with gross hematuria and
      focal bilateral renal masses as presenting features of a mature high-grade B-cell
      leukemia, Burkitt subtype. The patient was treated with standard chemotherapy
      with the addition of rituximab and has no evidence of disease on completion. To
      our knowledge, this is the first case to describe gross hematuria in conjunction
      with focal bilateral renal masses as presenting features in a pediatric patient
      with Burkitt leukemia. This unique presentation suggests that early leukemic
      infiltration of the urinary collecting system may occur but is extremely unusual.

PMID- 25559722
TI  - Impact of removable dentures on oral health-related quality of life among elderly
      adults in Taiwan.
AB  - BACKGROUND: Although the use of removable dentures can improve oral function and
      esthetics for elderly people, compared to those who do not wear removable
      dentures, those wearing removable dentures could have worse oral health related
      quality of life (OHRQoL). Additional information is required to assess which
      factors related to denture wearing influence the OHRQoL of elderly individuals.
      The purpose of this study is to evaluate the association between denture wearing
      and OHRQoL in a sample of elderly individuals in Taiwan. METHODS: The study
      population included 277 elderly people wearing removable dentures (mean age =
      76.0 years). Using face-to-face interviews, we collected data on the
      participants' socio-demographic characteristics, dental care service usage
      (regular dental checkups, treatment during toothache, dental visits in the last
      year), and factors related to denture wearing (perceived oral pain, perceived
      loose denture, perceived oral ulcer, perceived halitosis, perceived dry mouth,
      and perceived total denture satisfaction scores). OHRQoL was measured using the
      Taiwanese version of the Geriatric Oral Health Assessment Index (GOHAI-T). The
      location and number of remaining natural teeth and the type of denture were also
      recorded. Hierarchical multiple regression analysis was performed using GOHAI-T
      scores as the dependent variable. RESULTS: All the predictors together accounted
      for 50% of the variance in GOHAI-T scores. Further, education level, number of
      natural teeth, denture status, perceived loose denture, perceived oral ulcer, and
      perceived total denture satisfaction scores had statistically significant
      influences on OHRQoL. When compared with other variables, factors related to
      denture wearing, especially perceived total denture satisfaction scores, had the
      greatest impact on GOHAI-T scores. CONCLUSIONS: Of the factors analyzed in this
      study, denture satisfaction was the strongest predictor of OHRQoL. This suggests
      that denture satisfaction is useful for assessing the effect of denture treatment
      on the OHRQoL of elderly individuals wearing removable dentures.

PMID- 25559724
TI  - Incidental finding of right renal vein aneurysm in a patient with hematuria.
AB  - A 44-year-old man presented with hematuria. A diagnosis of right renal vein
      aneurysm without arteriovenous fistula and arteriovenous malformation was
      confirmed using computed tomographic angiography and digital subtraction
      angiography. The patient refused further invasive treatment, and he was
      discharged and remained well during the 6 months follow-up. We reviewed 13 adult
      cases of renal vein aneurysms reported in the English-language literature. To our
      knowledge, this is the first review of such a novel disease.

PMID- 25559725
TI  - Cutaneous metastasis of micropapillary urothelial carcinoma.
AB  - A 59-year-old man presented with persistent skin rash found to be cutaneous
      metastasis from micropapillary urothelial carcinoma status post right radical
      nephroureterectomy and adjuvant chemotherapy. The skin metastasis appeared 2
      months after postchemotherapy imaging demonstrated complete radiographic
      response. Cutaneous metastases from primary genitourinary malignancies are very
      rare clinical entities associated with poor prognosis. Cutaneous metastases do
      not have distinctive gross appearance and are often misdiagnosed as common
      dermatologic disorders. It is imperative that urologists have high index of
      suspicion for metastasis in patients with persistent skin rash in the setting of
      advanced genitourinary malignancies. 

PMID- 25559726
TI  - Evaluation of salvage male transobturator sling placement following recurrent
      stress urinary incontinence after failed transobturator sling.
AB  - OBJECTIVE: To evaluate the outcome of patients treated with a salvage AdVance
      male sling after a failed primary transobturator sling placement. METHODS:
      Retrospective review of patients treated at our center with a primary and
      subsequent salvage AdVance sling. Success was defined as a dry safety pad or no
      pads (cured), or >50% improvement in pads used per day and patient satisfaction
      (improved). Early primary sling failures (<6 months) were compared with late (>=6
      months) failures with regard to continence outcomes. RESULTS: We identified 18
      patients who underwent a salvage AdVance sling placement at our institution.
      Overall success was 72% at 6 months postoperatively and 56% at a mean follow-up
      of 17.5 months, including 50% and 39% of patients who were dry at those same time
      periods. Patients failing late after their primary sling (n = 8) enjoyed improved
      outcomes with salvage sling placement compared with patients who failed early (n
      = 10) after the primary sling. At 6 months, more patients in the late primary
      failure group were cured (75% vs. 30%; P = .031). These improved cure rates
      remained significant through final follow-up with cure rates of 63% and 20%,
      respectively (P = .041). CONCLUSION: Salvage AdVance male sling is a viable
      treatment option after a failed primary sling procedure, especially in patients
      who demonstrated a prolonged efficacy period before primary sling failure.

PMID- 25559727
TI  - Impact of the 2012 American Urological Association vasectomy guidelines on
      postvasectomy outcomes in a military population.
AB  - OBJECTIVE: To evaluate the impact of the 2012 American Urological Association
      vasectomy guidelines on postvasectomy clinical outcomes in a highly mobile
      military cohort and compare these outcomes with those of civilian counterparts.
      METHODS: The records of service members who underwent vasectomy between January
      2008 and December 2013 and provided at least 1 postvasectomy semen analysis
      (PVSA) were analyzed in the context of the 2012 guidelines. Time to occlusive
      success, repeat PVSAs and vasectomies, and health care cost savings were compared
      between our prior definition of vasectomy success, which required azoospermia,
      and the 2012 criteria, which included rare nonmotile sperm. RESULTS: Of the 1623
      men who underwent vasectomy, 738 men (45%) failed to submit a PVSA, leaving 895
      men (55%) who provided at least 1 PVSA. A total of 1084 PVSAs were obtained in
      these men, who had a mean age of 37 +/- 6 years. Defining success as azoospermia
      on first PVSA resulted in a sterility rate of 69%. After application of the 2012
      guidelines, 845 patients (94%) achieved sterility by the first PVSA and more
      patients achieved sterility 60 days from vasectomy (96% vs 72%; P <.001).
      Inclusion of rare nonmotile sperm in our definition of success would have allowed
      228 men to forego a second PVSA and prevented 2 (0.002%) unnecessary vasectomies,
      a savings of $6297. CONCLUSION: PVSA compliance in our military cohort was
      similar to that of civilian counterparts. The American Urological Association
      vasectomy guidelines have the potential to decrease the number of repeat
      vasectomies and laboratory tests, improve the documented success rate, and
      increase follow-up compliance when applied to a military population.

PMID- 25559728
TI  - Refinement and validation of the urethral stricture score in categorizing
      anterior urethral stricture complexity.
AB  - OBJECTIVE: To update, simplify, and validate the UREThRAL Stricture Score (now
      called the U-score) for anterior urethral strictures, with the goal of using this
      system as a predictor of surgical complexity. METHODS: This is a retrospective
      review of 102 patients (test set) who underwent anterior urethroplasty at Barnes
      Jewish Hospital from 2009 to 2012 and a validation set of 96 patients from
      Northwestern University. The U-score was based on length (1-3 points), stricture
      number (1-2 points), location (1-2 points), and etiology (1-2 points) for a total
      ranging from 4 to 9. Excision and primary anastomosis, buccal mucosal graft, and
      augmented anterior urethroplasty were classified as low complexity, and double
      buccal mucosal graft, flap, or flap-graft combo were classified as high
      complexity. Operative time and estimated blood loss were used as surrogates of
      surgical complexity. RESULTS: Mean U-score for low-complexity surgeries was 5.2
      and for high complexity surgeries was 7.3. Factors that were associated with high
      complexity repairs included stricture etiology (trauma or idiopathic or
      iatrogenic vs inflammatory or hypospadias; P <=.0001), number (1 vs. >1; P =
      .003), location (penile vs. bulbar; P <.001), and length (<2 vs. 2-5 vs. >5 cm; P
      <.001). Increasing U-score correlated with increasing surgical complexity (P
      <=.0001). A linear relationship between U-score and operative time was observed
      (P = .0018). U-score did not correlate with estimated blood loss (P = .82). Among
      the validation data set, etiology (P = .0014), location (P <=.0001), stricture
      length (P <=.0001), and overall U-score (P <=.0001) correlated with surgical
      complexity. CONCLUSION: The U-score is a validated scale to describe the
      complexity of anterior urethral strictures that correlates with surgical time and
      complexity of procedure.

PMID- 25559729
TI  - Notch1 predicts recurrence and survival of patients with clear-cell renal cell
      carcinoma after surgical resection.
AB  - OBJECTIVE: To evaluate the prognostic significance of Notch1 activation in
      patients with clear-cell renal cell carcinoma (ccRCC). METHODS: We
      retrospectively enrolled 203 patients with ccRCC undergoing nephrectomy at
      Zhongshan Hospital of Fudan University between 2003 and 2004. Notch1 activation
      was assessed by immunohistochemical staining of the intracellular domain of
      Notch1 (ICN1) in specimens of patients. The Kaplan-Meier method, Cox regression
      models, and Harrell concordance index (C-index) calculation were used to evaluate
      the prognostic value of ICN1 expression and its association with
      clinicopathologic features. RESULTS: Tumor tissues from patients with advanced
      TNM stage and Fuhrman grade exhibited elevated ICN1 expression, which correlated
      positively with tumor size, Fuhrman grade, and tumor necrosis. Moreover, high
      ICN1 expression indicated poor overall survival and recurrence-free survival of
      patients with ccRCC. After backward elimination, ICN1 expression, as well as
      Fuhrman grade, Eastern Cooperative Oncology Group performance status, and TNM
      stage, was identified as an independent adverse prognostic factor for survival
      and recurrence. The predictive accuracy of well-established TNM, University of
      California Integrated Staging System, and Mayo Clinic stage, size, grade, and
      necrosis prognostic models was improved when ICN1 expression was added.
      Furthermore, a predictive nomogram was generated with identified independent
      prognosticators to assess patient survival at 5 years after surgery. CONCLUSION:
      Notch1 activation is a potential independent adverse prognostic biomarker for
      recurrence and survival of patients with ccRCC after nephrectomy.

PMID- 25559730
TI  - Clinical safety and efficacy of probiotic administration following burn injury.
AB  - Provision of probiotics has been limited postburn by questionable potential for
      bacterial translocation and risk of infection in an immune-compromised
      population. The purpose of this study was to evaluate the safety of probiotic
      administration in acutely burned, pediatric patients. Subjects were randomized to
      receive probiotic (n = 10) vs placebo (n = 10) twice daily. The investigational
      product was initiated within 10 days of burn, and daily supplementation continued
      until wound closure. Nursing staff was provided education regarding optimal
      procedures to minimize potential for study product cross contamination. Clinical
      outcomes (infection, antibiotic, antifungal, and operative days, tolerance, and
      mortality) were recorded. Length of stay was modified for burn size. Student's t
      test, chi test, and nonparametric Wilcoxon's rank-sum test were used for
      comparative analysis. No differences were noted (probiotic; placebo) for age (7.1
      +/- 2.2; 6.9 +/- 1.7), burn size (38.0 +/- 5.9; 45.5 +/- 4.45), full thickness
      (24.6 +/- 5.6; 32.1 +/- 5.4), postburn day admit (0.8 +/- 0.4; 1.1 +/- 0.4), or
      inhalation injury (10%; 20%). Infection days, antibiotic use, constipation, and
      emesis were similar between groups. Trends toward increased antifungal and
      laxative use as well as diarrhea incidence were evident in the controls (P <
      .30). Flatulence was statistically higher with probiotics. The control group
      trended toward higher requirement for excision/graft procedure. Medical length of
      stay was not significantly different between groups; however, time required to
      complete wound healing was shortened with probiotics. This study documents safety
      and provides preliminary efficacy data relative to probiotic supplementation
      postburn. 

PMID- 25559731
TI  - Pediatric toxic epidermal necrolysis: using SCORTEN and predictive models to
      predict morbidity when a focus on mortality is not enough.
AB  - Toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS) are rare yet
      severe exfoliative skin disorders. The authors examined the efficacy of
      predictive models for their use as prognostic indicators in pediatric SJS or TEN.
      Over a 15-year period, 41 patients <=18 years of age were identified and
      reviewed. Predictive models compared retrospectively to the observed mortality in
      the population included: SCORTEN (Score of Toxic Epidermal Necrolysis), Pediatric
      Index of Mortality 2, Pediatric Risk of Mortality III-24, and Abbreviated Burn
      Severity Index. Correlation coefficients and 95% confidence intervals were
      calculated for the following: acute hospital length of stay, days until wound
      closure, days of mechanical ventilation, number of infectious complications, and
      number of acute operative procedures. When calculated within the first 24 hours
      of admission, the four models predicted low rates of mortality, approaching our
      0% observed mortality, and also demonstrated a significant correlation between
      higher scores and the five chosen indicators of morbidity (P < .05). SCORTEN on
      day 3 of admission was statistically significant (P < .05) only when predicting
      the number of infectious complications and days of mechanical ventilation and was
      therefore felt to be less predictive than use of SCORTEN on admission. When
      calculated within the first day of admission of pediatric SJS or TEN patients,
      SCORTEN, Abbreviated Burn Severity Index, Pediatric Index of Mortality 2, and
      Pediatric Risk of Mortality III all significantly predict acute morbidity. This
      is the first time scoring systems have been assessed for their ability to predict
      mortality and morbidity in pediatric SJS or TEN despite its widely recognized,
      severe acute course of disease.

PMID- 25559732
TI  - Comorbidity-polypharmacy score predicts in-hospital complications and the need
      for discharge to extended care facility in older burn patients.
AB  - Advancing age is associated with increased mortality despite smaller burn size.
      Chronic conditions are common in the elderly with resulting polypharmacy. The
      Comorbidity-Polypharmacy Score (CPS) facilitates quantitative assessment of the
      severity of comorbid conditions, or physiologic age. Burn injury in older
      patients is associated with increasing morbidity and mortality and the CPS may be
      predictive of outcomes such as mortality, ICU and hospital LOS, complications,
      and final hospital disposition. Our goal was to evaluate the predictive value of
      CPS for outcomes in the elderly burn population. A retrospective study was
      undertaken of 920 burn patients with age >=45 admitted with acute burn injuries
      (January 1, 2006 to December 31, 2012). CPS was calculated by adding preinjury
      comorbidities and medications. Subjects were stratified into three groups
      according to CPS severity. Data collected included demographics, total body
      surface area burned (TBSA), presence of inhalation injury, ICU/hospital length of
      stay, complications, discharge disposition, and mortality. Univariate and
      multivariate analyses were performed. The mean age was 55.7; 72.9% were males;
      the mean initial TBSA was 6.93%; and mean CPS was 8.01. The risk of in-hospital
      complications is independently associated with CPS (OR 1.35). CPS (OR 1.81) was
      an independent predictor of discharge to a facility CPS but not of mortality.
      While increasing CPS was associated with lower TBSA, mortality remained
      unchanged. CPS is an independent predictor of in-hospital complications and need
      for transfer to extended care facilities in older burn patients, which can be
      determined at the stage of admission to help direct patient management.

PMID- 25559734
TI  - Kaposiform hemangioendothelioma: therapeutic efficacy for an enigmatic diagnosis.

PMID- 25559733
TI  - A multicenter study of preventable contact burns from glass fronted gas
      fireplaces.
AB  - Glass fronted gas fireplaces (GFGFs) have exterior surfaces that can reach
      extremely high temperatures. Burn injuries from contact with the glass front can
      be severe with long-term sequelae. The Consumer Product Safety Commission
      reported that these injuries are uncommon, whereas single-center studies indicate
      a much higher frequency. The purpose of this multi-institutional study was to
      determine the magnitude and severity of GFGF injuries in North America. Seventeen
      burn centers elected to participate in this retrospective chart review. Chart
      review identified 402 children <=10 years of age who sustained contact burns from
      contact with GFGF, who were seen or admitted to the study hospitals from January
      2006 to December 2010. Demographic, burn, treatment, and financial data were
      collected. The mean age of the study group was 16.8 +/- 13.3 months. The majority
      suffered burns to their hands (396, 98.5%), with burns to the face being the
      second, much less common site (14, 3.5%). Two hundred and sixty-nine required
      rehabilitation therapy (66.9%). The number of GFGF injuries reported was 20 times
      greater than the approximately 30 injuries estimated by the Consumer Product
      Safety Commission's 10-year review. For the affected children, these injuries are
      painful, often costly and occasionally can lead to long-term sequelae. Given that
      less than a quarter of burn centers contributed data, the injury numbers reported
      herein support a need for broader safety guidelines for gas fireplaces in order
      to have a significant impact on future injuries.

PMID- 25559735
TI  - Sphingomonas sp. is a novel cell culture contaminant.
AB  - A novel contaminant was isolated from Madin Darby Bovine Kidney (MDBK) cells. The
      organism was unable to grow on standard microbiological media by conventional
      techniques, but grew well in Dulbecco's Modified Eagle's Medium (DMEM) containing
      high glucose concentration. The organism formed a white biofilm on the bottom
      without any signs of turbidity. Upon genome sequence analysis of 16 S rDNA, the
      contaminant was identified as Sphingomonas sp. Shah, a member of the group alpha
      Proteobacteria. Neutral red dye uptake method confirmed clear cytotoxic potential
      of the bacterium on A-549 cells. The organism was capable of invading and
      infecting different mammalian cell lines: MDBK, ZZ-R, 293-T, A549, and HeLa
      cells. Infected cells showed a variety of cytopathic effects including
      vacuolation at perinuclear area, cytoplasmic granulation and membrane blebbing.
      Microscopic analysis of the infected cells revealed the presence of cytoplasmic
      vacuoles harboring motile organisms. Apparently local serum preparations seem to
      be the source of this contamination, which is imperceptibly passed on from one
      culture passage to the other and ultimately leading to serious cytopathic
      manifestations.

PMID- 25559737
TI  - Functionalization of metallic glasses through hierarchical patterning.
AB  - Surface engineering over multiple length scales is critical for electronics,
      photonics, and enabling multifunctionality in synthetic materials. Here, we
      demonstrate a sequential embossing technique for building multi-tier patterns in
      metals by controlling the size-dependent thermoplastic forming of metallic
      glasses. Sub-100 nm to millimeter sized features are sculpted sequentially to
      allow an exquisite control of surface properties. The process can be integrated
      with net-shaping to transfer functional patterns on three-dimensional metal
      parts. 

PMID- 25559738
TI  - The bridge between neuroscience and cognition must be tethered at both ends.

PMID- 25559736
TI  - The restrained expression of NF-kB in renal tissue ameliorates folic acid induced
      acute kidney injury in mice.
AB  - The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)
      represent family of structurally-related eukaryotic transcription factors which
      regulate diverse array of cellular processes including immunological responses,
      inflammation, apoptosis, growth & development. Increased expression of NF-kB has
      often been seen in many diverse diseases, suggesting the importance of genomic
      deregulation to disease pathophysiology. In the present study we focused on acute
      kidney injury (AKI), which remains one of the major risk factor showing a high
      rate of mortality and morbidity. The pathology associated with it, however,
      remains incompletely known though inflammation has been reported to be one of the
      major risk factor in the disease pathophysiology. The role of NF-kB thus seemed
      pertinent. In the present study we show that high dose of folic acid (FA) induced
      acute kidney injury (AKI) characterized by elevation in levels of blood urea
      nitrogen & serum creatinine together with extensive tubular necrosis, loss of
      brush border and marked reduction in mitochondria. One of the salient
      observations of this study was a coupled increase in the expression of renal,
      relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI).
      Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium
      (PDTC) lowered the expression of these transcription factors and ameliorated the
      aberrant renal function by decreasing serum creatinine levels. In conclusion, our
      results suggested that NF-kB plays a pivotal role in maintaining renal function
      that also involved regulating p53 levels during FA AKI. 

PMID- 25559740
TI  - Excited state proton transfer dynamics of thioacetamide in S2(pipi*) state:
      resonance Raman spectroscopic and quantum mechanical calculations study.
AB  - The photophysics and photochemistry of thioacetamide (CH3CSNH2) after excitation
      to the S2 electronic state were investigated by using resonance Raman
      spectroscopy in conjunction with the complete active space self-consistent field
      (CASSCF) method and density functional theory (DFT) calculations. The A-band
      resonance Raman spectra in acetonitrile, methanol, and water were obtained at
      299.1, 282.4, 266.0, 252.7, and 245.9 nm excitation wavelengths to probe the
      structural dynamics of thioacetamide in the S2 state. CASSCF calculations were
      done to determine the transition energies and structures of the lower-lying
      excited states, the conical intersection points CI(S2/S1) and CI(S1/S0), and
      intersystem crossing points. The structural dynamics of thioacetamide in the S2
      state was revealed to be along eight Franck-Condon active vibrational modes nu15,
      nu11, nu14, nu10, nu8, nu12, nu18, and nu19, mostly in the CC/CS/CN stretches and
      the CNH8,9/CCH5,6,7/CCN/CCS in-plane bends as indicated by the corresponding
      normal mode descriptions. The S2 -> S1 decay process via the S2/S1 conical
      intersection point as the major channel were excluded. The thione-thiol
      photoisomerization reaction mechanism of thioacetamide via the S2,FC -> S'1,min
      excited state proton transfer (ESPT) reaction channel was proposed. 

PMID- 25559739
TI  - Vaccines in the treatment of invasive candidiasis.
AB  - Candida albicans is the most common cause of hematogenously disseminated
      candidiasis, and this disease is particularly prevalent in immunocompromised
      patients. The mortality of invasive candidiasis remains 40% to 50% even with the
      proper treatment with current antifungal drugs. Recently, with the better
      understanding of host-fungus interactions, notable progress has been made in
      antifungal vaccine research. Most antifungal vaccines exert protection by
      inducing either (or both) B-cell and T-cell responses. Here we summarize the
      current available information on C. albicans vaccines, highlight the obstacles
      that researchers identified, and offer several suggestions. 

PMID- 25559741
TI  - Static friction scaling of physisorbed islands: the key is in the edge.
AB  - The static friction preventing the free sliding of nanosized rare gas solid
      islands physisorbed on incommensurate crystalline surfaces is not completely
      understood. Simulations modeled on Kr/Pb(111) highlight the importance and the
      scaling behavior of the island's edge contribution to static friction. 

PMID- 25559742
TI  - Design, synthesis and evaluation of isoxazolo[5,4-d]pyrimidin-4(5H)-one
      derivatives as antithrombotic agents.
AB  - A series of isoxazolo[5,4-d]pyrimidin-4(5H)-one derivatives have been designed
      and synthesized as novel antithrombotic agents. The 4-acetoxyl substituted
      derivative (6g) displays very strong FXa inhibitory activity (IC50=0.013MUM),
      excellent anticoagulant effect in human plasma (2*PT=2.12MUM) and high
      selectivity to thrombin and trypsin. Docking investigation of 6g with FXa protein
      revealed that the pyrimidone ring of 6g formed a pi-pi interaction with the
      phenyl ring of Tyr99, and the carbonyl group in the P1 moiety formed multiple
      hydrogen bonds to Ser214 and Trp215. These results showed that isoxazolo[5,4
      d]pyrimidin-4(5H)-one is an attractive scaffold for designing novel factor Xa
      inhibitors and 4-carbonyl substituted phenyl ring could be used as novel S1
      binding element. 

PMID- 25559743
TI  - Design and synthesis of novel carbazole tethered pyrrole derivatives as potent
      inhibitors of Mycobacterium tuberculosis.
AB  - A series of novel carbazole tethered pyrrole derivatives were designed by
      coupling core fragments of antitubercular agents, carbazole and substituted
      pyrrole in single molecular architecture. The synthesis of new analogues was
      achieved by FeCl3 mediated one pot three component condensation of 2
      nitrovinylcarbazoles with aryl or alkyl amines and dimethylacetylene
      dicarboxylate (DMAD). All the new analogues 5a-l and 6a-l were fully
      characterized by their NMR and mass spectral data. Among the twenty four new
      compounds screened for in vitro anti-mycobacterial activity against Mycobacterium
      tuberculosis H37Rv, dimethyl 1-(4-fluorophenyl)-4-(9-methyl-9H-carbazol-3-yl)-1H
      pyrrole-2,3-dicarboxylate (5b) was found to be most active with MIC 3.13MUg/mL
      and has shown low cytotoxicity. 

PMID- 25559744
TI  - Criminal behavior in frontotemporal dementia and Alzheimer disease.
AB  - IMPORTANCE: Neurodegenerative diseases can cause dysfunction of neural structures
      involved in judgment, executive function, emotional processing, sexual behavior,
      violence, and self-awareness. Such dysfunctions can lead to antisocial and
      criminal behavior that appears for the first time in the adult or middle-aged
      individual or even later in life. OBJECTIVE: To investigate the frequency and
      type of criminal behavior among patients with a diagnosed dementing disorder.
      DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective medical record
      review of 2397 patients who were seen at the University of California, San
      Francisco, Memory and Aging Center between 1999 and 2012, including 545 patients
      with Alzheimer disease (AD), 171 patients with behavioral variant of
      frontotemporal dementia (bvFTD), 89 patients with semantic variant of primary
      progressive aphasia, and 30 patients with Huntington disease. Patient notes
      containing specific keywords denoting criminal behavior were reviewed. Data were
      stratified by criminal behavior type and diagnostic groups. MAIN OUTCOMES AND
      MEASURES: Frequencies of criminal behavior and chi2 statistics were calculated.
      RESULTS: Of the 2397 patients studied, 204 (8.5%) had a history of criminal
      behavior that emerged during their illness. Of the major diagnostic groups, 42 of
      545 patients (7.7%) with AD, 64 of 171 patients (37.4%) with bvFTD, 24 of 89
      patients (27.0%) with semantic variant of primary progressive aphasia, and 6 of
      30 patients (20%) with Huntington disease exhibited criminal behavior. A total of
      14% of patients with bvFTD were statistically significantly more likely to
      present with criminal behavior compared with 2% of patients with AD (P < .001)
      and 6.4% were statistically significantly more likely to exhibit violence
      compared with 2% of patients with AD (P = .003). Common manifestations of
      criminal behavior in the bvFTD group included theft, traffic violations, sexual
      advances, trespassing, and public urination in contrast with those in the AD
      group, who commonly committed traffic violations, often related to cognitive
      impairment. CONCLUSIONS AND RELEVANCE: Criminal behavior is more common in
      patients with bvFTD and semantic variant of primary progressive aphasia than in
      those with AD and is more likely to be an early manifestation of the disorder.
      Judicial evaluations of criminality in the demented individual might require
      different criteria than the classic "insanity defense" used in the American legal
      system; these individuals should be treated differently by the law. The
      appearance of new-onset criminal behavior in an adult should elicit a search for
      frontal and anterior temporal brain disease and for dementing disorders.

PMID- 25559745
TI  - Expression of pERK and VEGFR-2 in advanced hepatocellular carcinoma and
      resistance to sorafenib treatment.
AB  - BACKGROUND & AIMS: The study aimed to evaluate the tissue expression of molecules
      involved in intracellular signalling pathways as predictors of response to
      sorafenib in advanced hepatocellular carcinoma (HCC). METHODS: We considered 77
      patients enrolled into three prospective trials of sorafenib treatment for whom
      pretreatment tumour tissue was available. The tissue expression of beta-catenin,
      glutamine synthetase (GS), phosphorylated extracellular signal regulated kinase
      (pERK), phosphorylated v-akt murine thymoma viral oncogene homolog (pAKT) and
      vascular endothelial growth factor receptor-2 (VEGFR-2) was analysed by
      immunostaining. Stains were scored semiquantitatively and compared with a
      reference group of 56 untreated HCCs. RESULTS: Overall, the expression of
      antigens was comparable between treated and untreated patients. Shorter
      progression-free survival (PFS) and overall survival (OS) were associated with
      increased pERK staining (>= 2+ scores) (PFS: 75th percentile 4.4 vs 8.4 months; P
      = 0.01; OS: 75th percentile 7.0 vs 15.0 months; P = 0.005) and VEGFR-2 staining
      (>= 2+ scores) (PFS: 75th percentile 3.8 vs 7.0 months; P = 0.039; OS: 75th
      percentile 6.3 vs 15.0 months; P = 0.004). At multivariate analysis, both pERK
      and VEGFR-2 staining maintained an independent effect on OS (HR 2.09; 95% CI,
      1.13-3.86, P = 0.019 and HR 2.28; 95% CI, 1.13-4.61, P = 0.021 respectively). No
      effect was observed for the other tested biomarkers. CONCLUSIONS: Elevated tissue
      expression of pERK and VEGFR-2 was predictive of poor outcome in advanced HCC
      treated with sorafenib.

PMID- 25559746
TI  - Semi-supervised learning of causal relations in biomedical scientific discourse.
AB  - BACKGROUND: The increasing number of daily published articles in the biomedical
      domain has become too large for humans to handle on their own. As a result, bio
      text mining technologies have been developed to improve their workload by
      automatically analysing the text and extracting important knowledge. Specific bio
      entities, bio-events between these and facts can now be recognised with
      sufficient accuracy and are widely used by biomedical researchers. However,
      understanding how the extracted facts are connected in text is an extremely
      difficult task, which cannot be easily tackled by machinery. RESULTS: In this
      article, we describe our method to recognise causal triggers and their arguments
      in biomedical scientific discourse. We introduce new features and show that a
      self-learning approach improves the performance obtained by supervised machine
      learners to 83.47% for causal triggers. Furthermore, the spans of causal
      arguments can be recognised to a slightly higher level that by using supervised
      or rule-based methods that have been employed before. CONCLUSION: Exploiting the
      large amount of unlabelled data that is already available can help improve the
      performance of recognising causal discourse relations in the biomedical domain.
      This improvement will further benefit the development of multiple tasks, such as
      hypothesis generation for experimental laboratories, contradiction detection, and
      the creation of causal networks.

PMID- 25559748
TI  - A U-system approach for predicting metabolic behaviors and responses based on an
      alleged metabolic reaction network.
AB  - BACKGROUND: Progress in systems biology offers sophisticated approaches toward a
      comprehensive understanding of biological systems. Yet, computational analyses
      are held back due to difficulties in determining suitable model parameter values
      from experimental data which naturally are subject to biological fluctuations.
      The data may also be corrupted by experimental uncertainties and sometimes do not
      contain all information regarding variables that cannot be measured for technical
      reasons. RESULTS: We show here a streamlined approach for the construction of a
      coarse model that allows us to set up dynamic models with minimal input
      information. The approach uses a hybrid between a pure mass action system and a
      generalized mass action (GMA) system in the framework of biochemical systems
      theory (BST) with rate constants of 1, normal kinetic orders of 1, and -0.5 and
      0.5 for inhibitory and activating effects, named Unity (U)-system. The U-system
      model does not necessarily fit all data well but is often sufficient for
      predicting metabolic behavior of metabolites which cannot be simultaneously
      measured, identifying inconsistencies between experimental data and the assumed
      underlying pathway structure, as well as predicting system responses to a
      modification of gene or enzyme. The U-system approach was validated with small,
      generic systems and implemented to model a large-scale metabolic reaction network
      of a higher plant, Arabidopsis. The dynamic behaviors obtained by predictive
      simulations agreed with actually available metabolomic time-series data,
      identified probable errors in the experimental datasets, and estimated probable
      behavior of unmeasurable metabolites in a qualitative manner. The model could
      also predict metabolic responses of Arabidopsis with altered network structures
      due to genetic modification. CONCLUSIONS: The U-system approach can effectively
      predict metabolic behaviors and responses based on structures of an alleged
      metabolic reaction network. Thus, it can be a useful first-line tool of data
      analysis, model diagnostics and aid the design of next-step experiments.

PMID- 25559747
TI  - Thyrotropin and obesity: increased adipose triglyceride content through glycerol
      3-phosphate acyltransferase 3.
AB  - Epidemiological evidence indicates that thyrotropin (TSH) is positively
      correlated with the severity of obesity. However, the mechanism remains unclear.
      Here, we show that TSH promoted triglyceride (TG) synthesis in differentiated
      adipocytes in a thyroid hormone-independent manner. Mice with subclinical
      hypothyroidism, which is characterized by elevated serum TSH but not thyroid
      hormone levels, demonstrated a 35% increase in the total white adipose mass
      compared with their wild-type littermates. Interestingly, Tshr KO mice, which had
      normal thyroid hormone levels after thyroid hormone supplementation, resisted
      high-fat diet-induced obesity. TSH could directly induce the activity of glycerol
      3-phosphate-acyltransferase 3 (GPAT3), the rate-limiting enzyme in TG synthesis,
      in differentiated 3T3-L1 adipocytes. However, following either the knockdown of
      Tshr and PPARgamma or the constitutive activation of AMPK, the changes to TSH
      triggered GPAT3 activity and adipogenesis disappeared. The over-expression of
      PPARgamma or the expression of an AMPK dominant negative mutant reversed the TSH
      induced changes. Thus, TSH acted as a previously unrecognized master regulator of
      adipogenesis, indicating that modification of the AMPK/PPARgamma/GPAT3 axis via
      the TSH receptor might serve as a potential therapeutic target for obesity. 

PMID- 25559749
TI  - What would be Usain Bolt's 100-meter sprint world record without Tyson Gay?
      Unintentional interpersonal synchronization between the two sprinters.
AB  - Despite the desire of athletes to separate themselves from their competitors, to
      be faster or better, their performance is often influenced by those they are
      competing with. Here we show that the unintentional or spontaneous interpersonal
      synchronization of athletes' movements may partially account for such performance
      modifications. We examined the 100-m final of Usain Bolt in the 12th IAAF World
      Championship in Athletics (Berlin, 2009) in which he broke the world record, and
      demonstrate that Usain Bolt and Tyson Gay who ran side-by-side throughout the
      race spontaneously and intermittently synchronized their steps. This finding
      demonstrates that even the most optimized individual motor skills can be
      modulated by the simple presence of another individual via interpersonal
      coordination processes. It extends previous research by showing that the hard
      constraints of individual motor performance do not overwhelm the occurrence of
      spontaneous interpersonal synchronization and open promising new research
      directions for better understanding and improving athletic performance.

PMID- 25559751
TI  - Synergistic toughening of graphene oxide-molybdenum disulfide-thermoplastic
      polyurethane ternary artificial nacre.
AB  - Inspired by the ternary structure of natural nacre, robust ternary artificial
      nacre is constructed through synergistic toughening of graphene oxide (GO) and
      molybdenum disulfide (MoS2) nanosheets via a vacuum-assisted filtration self
      assembly process. The synergistic toughening effect from high mechanical
      properties of GO and lubrication of MoS2 nanosheets is successfully demonstrated.
      Meanwhile, the artificial nacre shows high electrical conductivity. This approach
      for constructing robust artificial nacre by synergistic effect from GO and MoS2
      provides a creative opportunity for designing and fabricating integrated
      artificial nacre in the near future, and this kind of ternary artificial nacre
      has great potential applications in aerospace, flexible supercapacitor
      electrodes, artificial muscle, and tissue engineering. 

PMID- 25559750
TI  - Synaptic protein levels altered in vascular dementia.
AB  - INTRODUCTION: Cerebral ischaemia is the defining pathophysiological abnormality
      in most forms of vascular dementia (VAD), but the pathogenesis of the dementia
      remains poorly understood. In Alzheimer's disease (AD), there is early loss of
      synaptic proteins, but these have been little studied in VAD. MATERIALS AND
      METHODS: We measured synaptophysin, postsynaptic density protein 95 (PSD-95),
      drebrin, synaptosomal-associated protein 25 (SNAP-25) and vascular endothelial
      growth factor (VEGF) by enzyme-linked immunosorbent assays in superior temporal
      cortex from 11 patients with VAD and, initially, 11 non-dementia controls. We
      corrected for neuronal content by measurement of neuron-specific enolase. A
      further 11 controls were subsequently used in a validation study. Simulation of
      post-mortem delay found that PSD-95 was stable at 4 degrees C but declined
      slightly at RT. SNAP-25 and drebrin showed good post-mortem stability. Previous
      studies had shown good post-mortem preservation of synaptophysin and VEGF.
      RESULTS: The VAD cases had lower synaptophysin (but P > 0.05 in initial study),
      significantly lower SNAP-25 (P = 0.024) and significantly higher drebrin (P =
      0.020). On comparison with the second control group, the reduction in
      synaptophysin was significant (P = 0.008), and the other results were confirmed.
      CONCLUSION: There is probably a reduction in presynaptic proteins in the temporal
      cortex in VAD, although not as marked as in AD. In VAD, there is also an increase
      in drebrin, which may be a response to reduced synaptic input.

PMID- 25559752
TI  - Gastric paraganglioma: a case report and a review of the literature.
AB  - AIM: Paragangliomas are neural crest-derived neuroendocrine tumors, originating
      from paraganglia, which are dispersed neuroendocrine organs characterized by
      catecholamine and peptide-producing cells. With an annual incidence estimated at
      1/100,000, paragangliomas represent 10% of catecholamine secreting tumors.
      MATERIAL OF STUDY: We report a case of a 76-year-old man who was submitted to a
      subtotal gastrectomy with omentectomy and gastrojejunal anastomosis. The
      Hystologic exam has revealed an ulcerative polypoid gastric carcinoma with cell
      poorly cohesive and infiltration of the muscular gastric wall and an incidental
      parietal gastric lesion which was a paraganglioma with immunocytochemical
      investigations positive for NSE and negative for CD117, S100, CD34 e SMA.
      DISCUSSION: Pheochromocytoma indicates exclusively tumors arising from the
      adrenal medulla, while the extra-adrenal paraganglioma suggests tumors of the
      chromaffin cells with other locations. Gastric or paragastric localization, as in
      our case, is very rare for these neoplasms, and in literature there are only
      isolated case reports. Genetical predisposition is observed in 30% of these
      tumors and can be responsible of hereditary disease characterized for differences
      in tumor distribution, catecholamine production, risk of metastasis, and
      association with others types of tumors. CONCLUSION: In asymptomatic patients and
      when biochemical and clinical suspicion of neuroendocrine tumor is strong, you
      have to perform anatomical and functional investigations to detect these
      neoplasms. The first line treatment for resectable tumors is complete surgical
      resection, that can be performed with open surgery or laparoscopic technique.
      Surgical therapy is also indicated to palliative intent when a complete
      eradication of disease is not achievable for metastatic status of malignancies.

PMID- 25559753
TI  - No differential effects of divergent isocaloric supplements on signaling for
      muscle protein turnover during recovery from muscle-damaging eccentric exercise.
AB  - Unaccustomed high-intensity eccentric exercise (ECC) can provoke muscle damage
      including several days of muscle force loss. Post-exercise dietary
      supplementation may provide a strategy to accelerate rate of force regain by
      affecting mechanisms related to muscle protein turnover. The aim of the current
      study was to investigate if protein signaling mechanisms involved in muscle
      protein turnover would be differentially affected by supplementation with either
      whey protein hydrolysate and carbohydrate (WPH+CHO) versus isocaloric
      carbohydrate (CHO) after muscle-damaging ECC. Twenty-four young healthy
      participants received either WPH+CHO (n = 12) or CHO supplements (n = 12) during
      post-exercise recovery from 150 maximal unilateral eccentric contractions. Prior
      to, at 3 h and at 24, 48, 96 and/or 168 h post-exercise, muscle strength, muscle
      soreness, and Akt-mTOR and FOXO signaling proteins, were measured in an ECC
      exercising leg and in the contralateral non-exercise control leg (CON). After
      ECC, muscle force decreased by 23-27 % at 24 h post-exercise, which was followed
      by gradual, although not full recovery at 168 h post-exercise, with no
      differences between supplement groups. Phosphorylation of mTOR, p70S6K and rpS6
      increased and phosphorylation of FOXO1 and FOXO3 decreased in the ECC leg, with
      no differences between supplement groups. Phosphorylation changes were also
      observed for rpS6, FOXO1 and FOXO3a in the CON leg, suggesting occurrence of
      remote tissue effects. In conclusion, divergent dietary supplementation types did
      not produce differences in signaling for muscle turnover during recovery from
      muscle-damaging exercise. 

PMID- 25559754
TI  - Predictors of health-related quality of life and adherence in Crohn's disease and
      ulcerative colitis: implications for clinical management.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is associated with impaired
      health-related quality of life (HRQOL) and adherence. Our aim was to identify
      demographic, clinical, and psychosocial predictors of impaired HRQOL and non
      adherence to provider recommendations. METHODS: Adults with Crohn's disease (CD)
      or ulcerative colitis (UC) residing within the USA were recruited from online IBD
      support groups for participation in this cross-sectional study. Data were
      collected online through standardized instruments, including the Inflammatory
      Bowel Disease Questionnaire and the Medical Outcomes Study (MOS) general
      adherence scale. Bivariate analyses and multivariate linear regression were used
      to assess predictors of HRQOL and adherence. RESULTS: We recruited 136
      individuals, among whom median age was 35 years (range 18-75), and 82 % were
      female. 57 % had CD, and 43 % had UC. Predictors of lower HRQOL among CD patients
      were perceived stress (p < 0.0001), number of CD relapses (p < 0.0001), and
      female gender (p = 0.0015), while among UC patients they were perceived stress (p
      < 0.0001) and number of UC relapses (p = 0.0017). Predictors of lower adherence
      to provider recommendations in CD were perceived stress (p = 0.0007) and older
      age (p = 0.041), while in UC, perceived stress was the only predictor of lower
      adherence (p = 0.022). CONCLUSIONS: Among patients with IBD, a higher level of
      perceived stress is a strong predictor of lower HRQOL and lower adherence to
      provider recommendations. Additionally, females with CD and patients with higher
      number of IBD relapses may be at risk of lower HRQOL. Psychological
      interventions, including physician-facilitated conversations, psychological
      screeners, and a multidisciplinary approach, may help address impaired HRQOL and
      adherence and merit further study.

PMID- 25559755
TI  - A critical analysis of the effect of view mode and frame rate on reading time and
      lesion detection during capsule endoscopy.
AB  - BACKGROUND AND AIM: Factors influencing reading time and detection of lesions
      include the view mode (VM) and frame rate (FR) applied during reading of small
      bowel capsule endoscopy images. The aims of this study were to examine the impact
      of VM and FR on reading time and lesion detection using a standardized, single
      type lesion model. METHODS: A selected video clip containing a known number of
      positive images (n = 60) of small bowel angioectasias was read using nine
      different combinations of VM and FR (VM1, VM2, and VM4 * FR10, FR15, and FR25) in
      randomized order by six capsule endoscopists. Readers were asked to count all
      positive images of angioectasias (maximum number of positive images, MPIs) seen
      during reading. The main outcome measurements were effect of VM and FR on reading
      time and lesion detection. RESULTS: Mean MPIs for all VM2 and VM4 were 36 (60 %)
      and 38 (64 %). They were significantly higher than VM1 of 24 (40 %) (P = 0.011,
      0.008). A statistical difference was found when the total MPIs at FR10 were
      compared to FR15 (P = 0.008) and to FR25 (P < 0.001). CONCLUSIONS: Both VM and FR
      significantly influence lesion detection during capsule endoscopy reading.

PMID- 25559756
TI  - Coexisting liver disease is associated with increased mortality after surgery for
      diverticular disease.
AB  - BACKGROUND: Coexistence of liver disease in patients undergoing surgery for
      diverticular disease (DD) may increase the risk of postoperative complications,
      but the evidence is limited. AIM: To investigate the impact of liver disease on
      mortality and reoperation rates following surgery for DD. METHODS: We performed a
      cohort study based on medical databases of all patients undergoing surgery for DD
      in Denmark during 1977-2011, categorizing them into three cohorts according to
      history of liver disease: patients with non-cirrhotic liver disease, those with
      liver cirrhosis, and those without liver disease (comparison cohort). Using the
      Kaplan-Meier method, we computed mortality in each cohort for 0-30, 31-60, and 61
      90 days following surgery for DD. We used a Cox regression model to compute
      hazard ratios as measures of the relative risk (RR) of death, controlling for
      potential confounders, including other comorbidities. In addition, we assessed
      the reoperation rate within 30 days of initial surgery. RESULTS: Of 14,408
      patients undergoing surgery for DD, 233 (1.6 %) had non-cirrhotic liver disease
      and 91 (0.6 %) had liver cirrhosis. Thirty-day mortality was 9.9 % in patients
      without liver disease and 14.6 % in patients with non-cirrhotic liver disease
      [adjusted RR = 1.64 (95 % confidence interval [CI] 1.16-2.31)]. Among patients
      with liver cirrhosis, mortality was 24.2 % [adjusted RR = 2.70 (95 % CI 1.73
      4.22)]. Liver cirrhosis had an impact on mortality up to 60 days after surgery
      for DD. The reoperation rate was approximately 10 % in each cohort. CONCLUSION:
      Preexisting liver disease has a major impact on postoperative mortality following
      surgery for DD.

PMID- 25559757
TI  - Severe drug-induced skin and liver injury from rivaroxaban.

PMID- 25559758
TI  - Hospital volume status is related to technical failure and all-cause mortality
      following ERCP for benign disease.
AB  - BACKGROUND: Population-based data on hospital procedure volume and outcome of
      endoscopic retrograde cholangiopancreatography (ERCP) are limited. AIMS: To
      investigate procedural failure, early re-admission, and all-cause mortality
      following ERCP performed due to benign disease and to examine their relation to
      hospital procedure volume. METHODS: All patients with a first ERCP in 2005-2008
      in Sweden were identified from the Swedish Hospital Discharge Registry. Data on
      indication, admission method, length of stay (LOS), and comorbid illness were
      extracted. Patients were linked to the Swedish Death and Cancer Registries.
      Factors associated with failed index ERCP, early re-admission, and all-cause
      mortality were identified by multiple logistic analyses. RESULTS: Overall, 12,695
      first ERCPs for benign disease were analyzed. The 30-day re-admission rate was 13
      % and all-cause 30-day mortality 2.2 %. Failed index ERCP was more common in low
      volume than high-volume institutions (p = 0.007). In logistic regression
      analysis, low hospital procedure volume was an independent predictor of failed
      index ERCP (odds ratio (OR) 2.72 vs. high), but not 30-day re-admission (p >
      0.05). LOS was longer in cases of procedural failure (p < 0.001). All-cause 30
      day mortality was independently related to low hospital ERCP volume (OR 1.41 vs.
      high) and failed ERCP (OR 5.65 vs. successful). CONCLUSION: In this population
      based cohort of first ERCPs due to benign disease, lower hospital ERCP volume was
      related to failed ERCP, which, in turn, was associated with longer LOS. Failed
      ERCP and lower hospital procedure volume were associated with poor survival, but
      not with early re-admission following index ERCP. These findings may have
      implications for service development.

PMID- 25559759
TI  - Insulin-mimetic selaginellins from Selaginella tamariscina with protein tyrosine
      phosphatase 1B (PTP1B) inhibitory activity.
AB  - As part of an ongoing search for new antidiabetic agents from medicinal plants,
      three new (2, 4, and 5) and two known selaginellin derivatives (1 and 3) were
      isolated from a methanol extract of Selaginella tamariscina. The structures of
      the new compounds were determined by spectroscopic data analysis. All isolates
      showed strong glucose uptake stimulatory effects in 3T3-L1 adipocyte cells at a
      concentration of 5 MUM. Furthermore, these compounds were found to possess
      inhibitory effects on PTP1B enzyme activity with IC50 values ranging from 4.6 +/-
      0.1 to 21.6 +/- 1.5 MUM. Compound 2 showed the greatest potency, with an IC50
      value of 4.6 +/- 0.1 MUM, when compared with the positive control (ursolic acid,
      IC50 = 3.5 +/- 0.1 MUM). Therefore, these selaginellin derivatives may have value
      as new lead compounds for the development of agents against type 2 diabetes. 

PMID- 25559760
TI  - Detection and modelling of contacts in explicit finite-element simulation of soft
      tissue biomechanics.
AB  - PURPOSE: Realistic modelling of soft tissue biomechanics and mechanical
      interactions between tissues is an important part of biomechanically-informed
      surgical image-guidance and surgical simulation. This submission details a
      contact-modelling pipeline suitable for implementation in explicit matrix-free
      FEM solvers. While these FEM algorithms have been shown to be very suitable for
      simulation of soft tissue biomechanics and successfully used in a number of image
      guidance systems, contact modelling specifically for these solvers is rarely
      addressed, partly because the typically large number of time steps required with
      this class of FEM solvers has led to a perception of them being a poor choice for
      simulations requiring complex contact modelling. METHODS: The presented algorithm
      is capable of handling most scenarios typically encountered in image-guidance.
      The contact forces are computed with an evolution of the Lagrange-multiplier
      method first used by Taylor and Flanagan in PRONTO 3D extended with spatio
      temporal smoothing heuristics for improved stability and edge-edge collision
      handling, and a new friction model. For contact search, a bounding-volume
      hierarchy (BVH) is employed, which is capable of identifying self-collisions by
      means of the surface-normal bounding cone of Volino and Magnenat-Thalmann, in
      turn computed with a novel formula. The BVH is further optimised for the small
      time steps by reducing the number of bounding-volume refittings between
      iterations through identification of regions with mostly rigid motion and
      negligible deformation. Further optimisation is achieved by integrating the self
      collision criterion in the BVH creation and updating algorithms. RESULTS: The
      effectiveness of the algorithm is demonstrated on a number of artificial test
      cases and meshes derived from medical image data. It is shown that the proposed
      algorithm reduces the cost of BVH refitting to the point where it becomes a
      negligible part of the overall computation time of the simulation. It is also
      shown that the proposed surface-normal cone computation formula leads to about 40
      % fewer BVH subtrees that must be checked for self-collisions compared with the
      widely used method of Provot. The proposed contact-force formulation and friction
      model are evaluated on artificial test cases that allow for a comparison with a
      ground truth. The quality of the proposed contact forces is assessed in terms of
      trajectories and energy conservation; a [Formula: see text]0.4 % drop off in
      total energy and highly plausible trajectories are found in the experiments. The
      friction model is evaluated through a benchmark problem with an analytical
      solution and a maximum displacement error of 8.2 %, and excellent agreement in
      terms of the stick/slip boundary is found. Finally, we show with realistic image
      guidance examples that the entire contact-modelling pipeline can be executed
      within a timeframe that is of the same order of magnitude as that required for
      standard FEM computations.

PMID- 25559761
TI  - Kinetic simulation of malate-aspartate and citrate-pyruvate shuttles in
      association with Krebs cycle.
AB  - In the present work, we have kinetically simulated two mitochondrial shuttles,
      malate-aspartate shuttle (used for transferring reducing equivalents) and citrate
      pyruvate shuttle (used for transferring carbon skeletons). However, the functions
      of these shuttles are not limited to the points mentioned above, and they can be
      used in different arrangements to meet different cellular requirements. Both the
      shuttles are intricately associated with Krebs cycle through the metabolites
      involved. The study of this system of shuttles and Krebs cycle explores the
      response of the system in different metabolic environments. Here, we have
      simulated these subsets individually and then combined them to study the
      interactions among them and to bring out the dynamics of these pathways in focus.
      Four antiports and a pyruvate pump were modelled along with the metabolic
      reactions on both sides of the inner mitochondrial membrane. Michaelis-Menten
      approach was extended for deriving rate equations of every component of the
      system. Kinetic simulation was carried out using ordinary differential equation
      solver in GNU Octave. It was observed that all the components attained steady
      state, sooner or later, depending on the system conditions. Progress curves and
      phase plots were plotted to understand the steady state behaviour of the
      metabolites involved. A comparative analysis between experimental and simulated
      data show fair agreement thus validating the usefulness and applicability of the
      model. 

PMID- 25559762
TI  - Developing a patient-directed policy framework for managing orphan and ultra
      orphan drugs throughout their lifecycle.
AB  - INTRODUCTION: Policy decisions related to orphan and ultra-orphan drugs challenge
      traditional decision-making processes and often frustrate those affected by them.
      In general, these drugs are associated with significant uncertainties around
      clinical benefit, 'value for money', affordability, and 'adoption/diffusion', all
      of which arise from a lack of available high-quality evidence. Increasingly,
      patients with rare diseases and their families are looking for opportunities to
      contribute to initiatives aimed at reducing these uncertainties. Therefore, a
      policy framework for guiding their involvement is needed to optimize the impact
      of any evidence generated. OBJECTIVES: The aims of this study were (1) to explore
      opportunities for patient involvement in reducing decision uncertainties
      throughout the lifecycle of orphan and ultra-orphan drugs from the perspectives
      of patients within the Canadian rare disease community; and (2) to develop a
      policy framework for patient input that maximizes the impact of their involvement
      on decision uncertainties around orphan and ultra-orphan drugs. METHODS: Two one
      day conferences and four workshops involving patients and/or families from rare
      disease communities in Canada were held to discuss issues around orphan and ultra
      orphan drug development, access, and coverage, and identify opportunities for
      patient input to reduce related decision uncertainties. Their feedback and the
      findings from a recent literature review on patient involvement in rare diseases
      were combined into a draft policy framework based upon Kingdon's multiple streams
      model of decision making. The framework was presented to a group of patients and
      other stakeholders, including providers, pharmaceutical drug plan managers, and
      industry representatives, and then revised accordingly. RESULTS: Patients and
      family members/caregivers identified tangible ways of contributing to the
      generation of information at all stages of the drug lifecycle. However, the
      proximity of that information to the reduction of a specific decision uncertainty
      varied. While the scope of possible ways mentioned was less broad when compared
      with the findings of the literature review, the focus was similar-capturing the
      clinical benefit of an orphan or ultra-orphan drug. A policy framework comprising
      three stages, each with a key question and corresponding set of sub-questions to
      be asked by patients, was developed. The three main sequential questions were as
      follows. (1) What uncertainties need to be addressed? (2) What roles should
      patients play? (3) Is each role feasible? CONCLUSIONS: Reducing decision
      uncertainties around orphan and ultra-orphan drugs requires a policy framework
      that explicates when and what type of information needs to be generated, and
      recognizes the role of patients as important sources of such information
      throughout the lifecycle of these drugs.

PMID- 25559764
TI  - Painless shoulder mass.

PMID- 25559765
TI  - Endoscopic versus surgical cystogastrostomy for pancreatic pseudocysts.

PMID- 25559763
TI  - Angiotensin-(1-7) attenuates airway remodelling and hyperresponsiveness in a
      model of chronic allergic lung inflammation.
AB  - BACKGROUND AND PURPOSE: A long-term imbalance between pro- and anti-inflammatory
      mediators leads to airway remodelling, which is strongly correlated to most of
      the symptoms, severity and progression of chronic lung inflammation. The
      Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis of the renin-angiotensin system
      is associated with attenuation of acute and chronic inflammatory processes. In
      this study, we investigated the effects of Ang-(1-7) treatment in a model of
      chronic allergic lung inflammation. EXPERIMENTAL APPROACH: Mice were sensitized
      to ovalbumin (OVA; 4 injections over 42 days, 14 days apart) and were challenged
      three times per week (days 21-46). These mice received Ang-(1-7) (1 MUg.h(-1) ,
      s.c.) by osmotic mini-pumps, for the last 28 days. Histology and morphometric
      analysis were performed in left lung and right ventricle. Airway responsiveness
      to methacholine, analysis of Ang-(1-7) levels (RIA), collagen I and III (qRT
      PCR), ERK1/2 and JNK (Western blotting), IgE (elisa), cytokines and chemokines
      (elisa multiplex), and immunohistochemistry for Mas receptors were performed. KEY
      RESULTS: Infusion of Ang-(1-7) in OVA-sensitized and challenged mice decreased
      inflammatory cell infiltration and collagen deposition in the airways and lung
      parenchyma, and prevented bronchial hyperresponsiveness. These effects were
      accompanied by decreased IgE and ERK1/2 phosphorylation, and decreased pro
      inflammatory cytokines. Mas receptors were detected in the epithelium and
      bronchial smooth muscle, suggesting a site in the lung for the beneficial actions
      of Ang-(1-7). CONCLUSIONS AND IMPLICATIONS: Ang-(1-7) exerted beneficial
      attenuation of three major features of chronic asthma: lung inflammation, airway
      remodelling and hyperresponsiveness. Our results support an important protective
      role of Ang-(1-7) in lung inflammation.

PMID- 25559766
TI  - Dexmedetomidine vs midazolam as preanesthetic medication in children: a meta
      analysis of randomized controlled trials.
AB  - INTRODUCTION: The preoperative period is a stressing occurrence for most people
      undergoing surgery, in particular children. Approximately 50-75% of children
      undergoing surgery develop anxiety which is associated with distress on emergence
      from anesthesia and with later postoperative behavioral problems. Premedication,
      commonly performed with benzodiazepines, reduces preoperative anxiety,
      facilitates separation from parents, and promotes acceptance of mask induction.
      Dexmedetomidine is a highly selective alpha2 -agonist with sedative and analgesic
      properties. A meta-analysis of all randomized controlled trials (RCTs) on
      dexmedetomidine versus midazolam was performed to evaluate its efficacy in
      improving perioperative sedation and analgesia, and in reducing postoperative
      agitation when used as a preanesthetic medication in children. METHODS: Studies
      were independently searched in PubMed, BioMedCentral, Embase, and the Cochrane
      Central Register of clinical trials and updated on August 15th, 2014. Primary
      outcomes were represented by improved sedation at separation from parents, at
      induction of anesthesia, and reduction in postoperative agitation. Secondary
      outcomes were reduction in rescue analgesic drugs, and duration of surgery and
      anesthesia. Inclusion criteria were random allocation to treatment and comparison
      between dexmedetomidine and midazolam. Exclusion criteria were adult studies,
      duplicate publications, intravenous administration, and no data on main outcomes.
      RESULTS: Data from 1033 children in 13 randomized trials were analyzed. Overall,
      in the dexmedetomidine group there was a higher incidence of satisfactory
      sedation at separation from parents (314 of 424 [74%] in the dexmedetomidine
      group vs 196 of 391 [50%] in the midazolam group, RR = 1.30 [1.05-1.62], P =
      0.02), a reduced incidence of postoperative agitation (14 of 140 [10%] vs 56 of
      141 [40%], RR = 0.31 [0.13-0.73], P = 0.008), and a significant reduction in the
      rescue doses of analgesic drugs (49 of 241 [20%] vs 95 of 243 [39%], RR = 0.52
      [0.39-0.70], P < 0.001). There was no evidence of a higher incidence of
      satisfactory sedation at anesthesia induction or any reduction of duration of
      surgery and anesthesia. CONCLUSIONS: Dexmedetomidine is effective in decreasing
      anxiety upon separation from parents, decreasing postoperative agitation, and
      providing more effective postoperative analgesia when compared with midazolam.

PMID- 25559767
TI  - Characterization of the neuroprotective potential of derivatives of the iron
      chelating drug deferiprone.
AB  - There is growing evidence for alterations in iron homeostasis during aging that
      are exacerbated in neurodegenerative diseases such as Alzheimer's disease.
      However, since essentially all neurodegenerative diseases are multi-factorial in
      the sense that there are a large number of mechanisms that can be identified as
      contributing to nerve cell death, iron chelators that have additional activities
      might be the most useful for the treatment of age-related CNS diseases. We have
      described a series of cell culture-based assays that define molecular toxicity
      pathways relevant to neurodegenerative diseases and have used these assays to
      identify potential therapeutic compounds for the treatment of these diseases.
      Deferiprone is a blood brain barrier permeable, low molecular weight iron
      chelator that has been used for many years to treat systemic iron disease. In
      this study, we describe the use of our cell culture-based screening assays to
      identify deferiprone derivatives with the greatest therapeutic potential for the
      treatment of CNS diseases. We show that several derivatives are much more potent
      than deferiprone at reducing oxidative stress and preventing nerve cell death
      induced by multiple, age-related insults. In addition, we show that both
      deferiprone and the derivatives modulate several distinct signaling pathways
      associated with neuroprotection. All of the compounds were able to both inhibit
      the activation of p38 MAP kinase and JNK kinase and prevent the loss of PI3
      kinase activity in response to a toxic stress. These results strongly suggest
      that these compounds have significant potential for the treatment of CNS
      diseases. 

PMID- 25559769
TI  - AucPR: an AUC-based approach using penalized regression for disease prediction
      with high-dimensional omics data.
AB  - MOTIVATION: It is common to get an optimal combination of markers for disease
      classification and prediction when multiple markers are available. Many
      approaches based on the area under the receiver operating characteristic curve
      (AUC) have been proposed. Existing works based on AUC in a high-dimensional
      context depend mainly on a non-parametric, smooth approximation of AUC, with no
      work using a parametric AUC-based approach, for high-dimensional data. RESULTS:
      We propose an AUC-based approach using penalized regression (AucPR), which is a
      parametric method used for obtaining a linear combination for maximizing the AUC.
      To obtain the AUC maximizer in a high-dimensional context, we transform a
      classical parametric AUC maximizer, which is used in a low-dimensional context,
      into a regression framework and thus, apply the penalization regression approach
      directly. Two kinds of penalization, lasso and elastic net, are considered. The
      parametric approach can avoid some of the difficulties of a conventional non
      parametric AUC-based approach, such as the lack of an appropriate concave
      objective function and a prudent choice of the smoothing parameter. We apply the
      proposed AucPR for gene selection and classification using four real microarray
      and synthetic data. Through numerical studies, AucPR is shown to perform better
      than the penalized logistic regression and the nonparametric AUC-based method, in
      the sense of AUC and sensitivity for a given specificity, particularly when there
      are many correlated genes. CONCLUSION: We propose a powerful parametric and
      easily-implementable linear classifier AucPR, for gene selection and disease
      prediction for high-dimensional data. AucPR is recommended for its good
      prediction performance. Beside gene expression microarray data, AucPR can be
      applied to other types of high-dimensional omics data, such as miRNA and protein
      data.

PMID- 25559771
TI  - Relative efficacy and safety of simeprevir and telaprevir in treatment-naive
      hepatitis C-infected patients in a Japanese population: A Bayesian network meta
      analysis.
AB  - AIM: Simeprevir (SMV) is an oral, once-daily protease inhibitor for the treatment
      of chronic hepatitis C virus (HCV) genotype 1 infection. In phase II/III
      randomized controlled trials (RCT) conducted in Japan, SMV, in combination with
      peginterferon-alpha and ribavirin (PEG IFN/RBV), demonstrated potent efficacy in
      HCV genotype 1-infected patients relative to PEG IFN/RBV and was generally well
      tolerated. Telaprevir (TVR) in combination with PEG IFN/RBV is licensed for the
      treatment of HCV in Japan. In the absence of head-to-head comparisons of TVR and
      SMV in a Japanese population, we undertook a network meta-analysis (NMA) to
      examine the relative efficacy and safety of SMV and TVR in combination with PEG
      IFN/RBV. METHODS: A systematic review identified SMV and TVR RCT in Japanese
      treatment-naive patients. Bayesian NMA was performed assuming fixed study
      effects. RESULTS: Three studies met our inclusion criteria: two SMV and one TVR.
      SMV showed a higher mean odds ratio (OR) of achieving SVR versus TVR (OR, 1.68
      (95% credible interval 0.66-4.26)). SMV showed a lower mean OR of
      discontinuation: overall, 0.35 (0.12-1.00); and due to AE, 0.87 (0.23-3.34)
      versus TVR. SMV showed a lower mean OR of experiencing anemia 0.20 (0.07-0.56)
      and rash 0.41 (0.17-0.99) but a higher mean OR of experiencing pruritus 1.26
      (0.46-3.47) versus TVR. CONCLUSION: In this indirect treatment comparison, SMV,
      in combination with PEG IFN/RBV, showed a favorable risk-benefit profile compared
      with TVR with PEG IFN/RBV in Japanese treatment-naive HCV patients.

PMID- 25559770
TI  - The insecticidal spider toxin SFI1 is a knottin peptide that blocks the pore of
      insect voltage-gated sodium channels via a large beta-hairpin loop.
AB  - Spider venoms contain a plethora of insecticidal peptides that act on neuronal
      ion channels and receptors. Because of their high specificity, potency and
      stability, these peptides have attracted much attention as potential
      environmentally friendly insecticides. Although many insecticidal spider venom
      peptides have been isolated, the molecular target, mode of action and structure
      of only a small minority have been explored. Sf1a, a 46-residue peptide isolated
      from the venom of the tube-web spider Segesteria florentina, is insecticidal to a
      wide range of insects, but nontoxic to vertebrates. In order to investigate its
      structure and mode of action, we developed an efficient bacterial expression
      system for the production of Sf1a. We determined a high-resolution solution
      structure of Sf1a using multidimensional 3D/4D NMR spectroscopy. This revealed
      that Sf1a is a knottin peptide with an unusually large beta-hairpin loop that
      accounts for a third of the peptide length. This loop is delimited by a fourth
      disulfide bond that is not commonly found in knottin peptides. We showed, through
      mutagenesis, that this large loop is functionally critical for insecticidal
      activity. Sf1a was further shown to be a selective inhibitor of insect voltage
      gated sodium channels, consistent with its 'depressant' paralytic phenotype in
      insects. However, in contrast to the majority of spider-derived sodium channel
      toxins that function as gating modifiers via interaction with one or more of the
      voltage-sensor domains, Sf1a appears to act as a pore blocker.

PMID- 25559768
TI  - Extracellular vesicles as carriers of microRNA, proteins and lipids in tumor
      microenvironment.
AB  - In recent years, the knowledge about the control of tumor microenvironment has
      increased and emerged as an important player in tumorigenesis. The role of normal
      stromal cells in the tumor initiation and progression has brought our vision in
      to the forefront of cell-to-cell communication. In this review, we focus on the
      mechanism of communication between stromal and tumor cells, which is based on the
      exchange of extracellular vesicles (EVs). We describe several, evergrowing,
      pieces of evidence that EVs transfer messages through their miRNA, lipid, protein
      and nucleic acid contents. A better understanding of this sophisticated method of
      communication between normal cancer cells may lead to developing novel approaches
      for personalized diagnostics and therapeutics. 

PMID- 25559772
TI  - The impact of depression on Veterans with PTSD and traumatic brain injury: a
      diffusion tensor imaging study.
AB  - A significant proportion of military personnel deployed in support of Operation
      Enduring Freedom and Operation Iraqi Freedom were exposed to war-zone events
      associated with traumatic brain injury (TBI), depression (DEP) and posttraumatic
      stress disorder (PTSD). The co-occurrence of TBI, PTSD and DEP in returning
      Veterans has recently increased research and clinical interest. This study tested
      the hypothesis that white matter abnormalities are further impacted by
      depression. Of particular relevance is the uncinate fasciculus (UF), which is a
      key fronto-temporal tract involved in mood regulation, and the cingulum; a tract
      that connects to the hippocampus involved in memory integration. Diffusion tensor
      imaging (DTI) was performed on 25 patients with a combination of PTSD, TBI and
      DEP and 20 patients with PTSD and TBI (no DEP). Microstructural changes of white
      matter were found in the cingulum and UF. Fractional anisotropy (FA) was lower in
      Veterans with DEP compared to those without DEP. 

PMID- 25559773
TI  - Heart rate variability during adolescent and adult social interactions: a meta
      analysis.
AB  - Social interaction skill is important for psychological wellbeing, stress
      regulation, protection from disability and overall life satisfaction. Increase in
      activity of the vagus nerve, measured by heart rate variability (HRV), is
      associated with social interaction skill and decreased stress. In this meta
      analysis we collated statistics from thirteen studies consisting of 787
      participants who were participating in social interactions while HRV was
      simultaneously collected. Results revealed that while dyadic social interactions
      do not increase HRV generally from a baseline state, negative dyadic social
      interactions decrease HRV in a manner similar to the Trier Social Stress Task.
      Further, participants with psychopathology do not show cardiac autonomic
      flexibility during social interactions as indicated by reductions under stress
      and increases with subsequently positive social interactions. The role of age,
      gender and HRV index were also examined as potential moderators of HRV.
      Implications for health and wellbeing resulting from exposure to negative social
      interactions are discussed. 

PMID- 25559774
TI  - Factors influencing hypertrophy of the left lateral liver lobe after portal vein
      embolization.
AB  - PURPOSE: Portal vein embolization (PVE) before extended right hepatectomy leads
      to an increase of the future liver remnant (FLR) volume, but predictive factors
      for sufficient hypertrophy are still unclear. The purpose of this study was to
      investigate parameters influencing the growth of FLR. METHODS: Patients
      undergoing PVE prior hepatic resection were evaluated. PVE was done using
      polyvinyl alcohol particles only. Volumetric analysis was performed before
      embolization and before hepatectomy. Success of PVE was determined as percental
      growth of the future liver remnant. RESULTS: Seventy-seven patients were
      included, and three cohorts were formed according to the hypertrophy of FLR. FLR
      increased from 448.2 +/- 187 to 475.5 +/- 191 in the poor, from 315.3 +/- 86 to
      469.1 +/- 142 in the moderate, and from 283.4 +/- 68 to 400.4 +/- 110 in the good
      hypertrophy group. More cases of recanalization of the portal vein were observed
      in patients with poor hypertrophy (p = 0.016). Small FLR before PVE predict
      higher growth of the FLR (p = 0.006). Duration between PVE and surgery differed
      significantly: 22 (poor) vs. 32 (good) days (p = 0.040). DISCUSSION: No
      recanalization, small initial FLR and longer time were assessed with better FLR
      hypertrophy. More sufficient PVE techniques and postponed hepatectomy might
      improve the outcome. Small initial FLR should not be a disclosure for curative
      hepatectomy.

PMID- 25559775
TI  - Mitochondrial functional impairment in response to environmental toxins in the
      cardiorenal metabolic syndrome.
AB  - Environmental toxins can promote cardiovascular, metabolic, and renal
      abnormalities, which characterize the cardiorenal metabolic syndrome (CRS). Heavy
      metals, such as mercury and arsenic, represent two of the most toxic pollutants.
      Exposure to these toxins is increasing due to increased industrialization
      throughout much of the world. Studies conducted to understand the impact of
      environmental toxins have shown a major impact on mitochondrial structure and
      function. The maladaptive stress products caused by these toxins, including
      aggregated proteins, damaged organelles, and intracellular pathogens, can be
      removed through autophagy, which is also known as mitophagy in mitochondria.
      Although the underlying mechanisms involved in the regulation of mitophagy in
      response to pollution are not well understood, accumulating evidence supports a
      role for maladaptive mitochondrial responses to environmental pollution in the
      pathogenesis of the CRS. In this review, we discuss the ongoing research, which
      explores the mechanisms by which these toxins promote abnormalities in mitophagy
      and associated mitochondrial dysfunction and the CRS. 

PMID- 25559777
TI  - A hole in the heart.

PMID- 25559778
TI  - Review on hazardous and noxious substances (HNS) involved in marine spill
      incidents-an online database.
AB  - In this review, we have collected information on the behavior, fate, weathering,
      and impact of hazardous and noxious substances (HNS) accidentally spilled at sea
      on the marine biota. The information was compiled on a datasheet and converted
      into a database that can be accessed by the general public
      (www.ciimar.up.pt/hns). Systematization of data is important to assist
      stakeholders involved in HNS spill preparedness and response, facilitating the
      incorporation of lessons from past incidents in the decision process. The
      database contains 184 entries of HNS spilled in 119 incidents in marine waters
      around the world. Data were analyzed in terms of HNS physical behavior in water
      according to SEBC (Standard European Behavior Classification) codes. The most
      common products involved in accidental spills in the marine environment were
      identified and major lessons highlighted. From the analysis, it was determined
      that most HNS spills were poorly documented and information was mistreated. In
      most cases, no monitoring programs were implemented following the incident. This
      conduct has occurred in 24 out of 119 incidents analyzed and has consequently
      limited the information on fate, behavior, and weathering of HNS spilled that
      could have been recovered. Major gaps were identified, and priorities and
      recommendations were drawn as a step toward improving preparedness and response
      to HNS spills. 

PMID- 25559779
TI  - Influence of coexisting spiramycin contaminant on the harm of Microcystis
      aeruginosa at different nitrogen levels.
AB  - The influence of nitrogen on the effects of the antibiotic contaminant spiramycin
      on Microcystis aeruginosa was studied through a 7-day exposure test. At current
      contamination levels of 0.5-100 mg L(-1) for nitrogen and 0.1-0.4 MUg L(-1) for
      spiramycin, the two factors significantly interacted with each other (p<0.05) on
      the synthesis of chlorophyll-a and protein, the production and release of
      microcystins as well as the expression of ntcA gene and mcyB gene in M.
      aeruginosa. Nitrogen significantly affected the toxicity of spiramycin on algal
      growth (p<0.05) via regulation of protein synthesis. The photosynthesis system
      including chlorophyll-a, the psbA gene, and the rbcL gene participated in stress
      responses to spiramycin. Coexisting spiramycin contaminant increased the harm of
      M. aeruginosa by stimulating the production and release of MCs at a nitrogen
      level of 0.5 mg L(-1), but alleviated M. aeruginosa pollution at higher nitrogen
      levels of 5-100 mg L(-1) by inhibiting algal growth, the production of
      microcystins and the expression of ntcA and mcyB. The nitrogen-dependent effects
      of spiramycin should be considered in the control of M. aeruginosa bloom in the
      presence of spiramycin.

PMID- 25559780
TI  - Efficacy of the Japanese herbal medicine rikkunshito in infants with
      gastroesophageal reflux disease.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) in infants is among the most
      common reason for physician consultation worldwide. A traditional Japanese
      medicine, rikkunshito (RKT), is effective for GERD in adult and pediatric
      patients. The aim of this study was to evaluate the efficacy and safety of RKT in
      infants with GERD. METHODS: Fifty-four infants were referred to between July 2004
      and December 2012 for evaluation and treatment of GERD. All infants had failure
      to thrive. We excluded nine patients with cow's milk protein allergy,
      neurological impairment or surgical indications. We retrospectively reviewed the
      clinical records of 45 infants with GERD. Twenty-nine infants were treated with
      RKT (TJ-43; 0.3 g/kg/day; RKT group), and 16 infants were treated with mosapride
      citrate at 0.5 mg/kg/day (mosapride group). The primary endpoint was RKT-induced
      relief of clinical symptoms and bodyweight gain in infants with GERD. RESULTS:
      After 3 months of treatment, the frequency of vomiting per day was significantly
      lower in the RKT group than in the mosapride group (P = 0.0146) and the weight Z
      score was significantly higher in the RKT group than in the mosapride group (RKT
      group, -2.5 +/- 1.5 vs mosapride group, -5.0 +/- 2.0; P = 0.0386). No adverse
      effects were noted in either group. CONCLUSIONS: RKT may be safe and effective
      for relief of GER symptoms and for bodyweight gain in infants with GERD.

PMID- 25559781
TI  - Development of a wearable multi-frequency impedance cardiography device.
AB  - Cardiovascular diseases as well as pulmonary oedema can be early diagnosed using
      vital signs and thoracic bio-impedance. By recording the electrocardiogram (ECG)
      and the impedance cardiogram (ICG), vital parameters are captured continuously.
      The aim of this study is the continuous monitoring of ECG and multi-frequency ICG
      by a mobile system. A mobile measuring system, based on 'low-power' ECG, ICG and
      an included radio transmission is described. Due to the high component
      integration, a board size of only 6.5 cm*5 cm could be realized. The measured
      data can be transmitted via Bluetooth and visualized on a portable monitor. By
      using energy-efficient hardware, the system can operate for up to 18 hs with a 3
      V battery, continuously sending data via Bluetooth. Longer operating times can be
      realized by decreased transfer rates. The relative error of the impedance
      measurement was less than 1%. The ECG and ICG measurements allow an approximate
      calculation of the heart stroke volume. The ECG and the measured impedance showed
      a high correlation to commercial devices (r=0.83, p<0.05). In addition to
      commercial devices, the developed system allows a multi-frequency measurement of
      the thoracic impedance between 5-150 kHz.

PMID- 25559776
TI  - The Hedgehog pathway: role in cell differentiation, polarity and proliferation.
AB  - Hedgehog (Hh) is first described as a genetic mutation that has "spiked"
      phenotype in the cuticles of Drosophila in later 1970s. Since then, Hh signaling
      has been implicated in regulation of differentiation, proliferation, tissue
      polarity, stem cell population and carcinogenesis. The first link of Hh signaling
      to cancer was established through discovery of genetic mutations of Hh receptor
      gene PTCH1 being responsible for Gorlin syndrome in 1996. It was later shown that
      Hh signaling is associated with many types of cancer, including skin, leukemia,
      lung, brain and gastrointestinal cancers. Another important milestone for the Hh
      research field is the FDA approval for the clinical use of Hh inhibitor
      Erivedge/Vismodegib for treatment of locally advanced and metastatic basal cell
      carcinomas. However, recent clinical trials of Hh signaling inhibitors in
      pancreatic, colon and ovarian cancer all failed, indicating a real need for
      further understanding of Hh signaling in cancer. In this review, we will
      summarize recent progress in the Hh signaling mechanism and its role in human
      cancer. 

PMID- 25559782
TI  - Is John Henryism a resilience factor in women experiencing intimate partner
      violence?
AB  - BACKGROUND: Research suggests that posttraumatic stress disorder (PTSD) and
      depression are two common mental health problems in intimate partner violence
      (IPV) survivors. Research has found that while Black women consistently report
      higher rates of victimization than White women, they also report less severe PTSD
      and depressive symptoms, suggesting that Black IPV survivors might be more
      resilient to PTSD and depression than are White survivors. DESIGN: We implemented
      a correlational study with 81 Black and 100 White female survivors of IPV to
      determine if John Henryism (JH; i.e., a predisposed active coping mechanism)
      contributes to the resilience observed in Black IPV survivors. METHODS:
      Participants completed the John Henryism Active Coping Scale, Center for
      Epidemiological Studies Depression Scale, Davidson Trauma Scale, and the Abusive
      Behavior Inventory. RESULTS: Results demonstrated that White woman endorsed more
      severe depressive symptoms as compared to Black women. Severity of PTSD symptoms
      and JH was not significantly different between races. JH did not moderate the
      relationship between race and depression; however, for PTSD, JH was found to be
      protective of PTSD in White women, while demonstrating little impact on Black
      women. CONCLUSIONS: The implications of these findings are discussed in terms of
      the minority stress model.

PMID- 25559783
TI  - Comparison between laparoscopically assisted and standard fetoscopic laser
      ablation in patients with anterior and posterior placentation in twin-twin
      transfusion syndrome: a single center study.
AB  - BACKGROUND: The objective of our study was to compare outcomes following
      laparoscopically assisted procedure (LAP group) with those seen following a
      standard approach used in patients with either an anterior placenta (SAP group)
      or posterior placenta (SPP group). METHOD: This was a retrospective review of all
      the cases of twin-twin transfusion syndrome treated in our fetal center from
      October 2011 to July 2013. Technical characteristics of the procedure, perinatal
      survival outcome, and maternal morbidity were compared. RESULTS: The laser
      procedure time was significantly longer in the SAP group (44 +/- 10 min) in
      contrast with SPP (19.3 +/- 13.9 min, p < 0.001) and LAP group (32 +/- 11 min, p:
      0.012). Preterm premature rupture of membranes (PPROM) before 32 and 34 weeks of
      pregnancy was significantly more common with LAP versus SAP and SPP (90 vs 33.3
      and 70.8% for 32 weeks respectively, p: 0.015; 100 vs 50 and 79.1% for 34 weeks
      respectively, p: 0.021). In terms of maternal morbidity and neonatal outcome,
      there were no significant differences between the three groups. CONCLUSION: LAP
      may be useful in cases where SAP is not feasible. Despite the increased risk of
      PPROM with LAP, perinatal survival and maternal outcomes are similar to that seen
      in SAP and SPP patients.

PMID- 25559784
TI  - Effect of Prophylactic Ankle-Brace Use During a High School Competitive
      Basketball Season on Dynamic Postural Control.
AB  - CONTEXT: Few studies have evaluated the long-term effects of prophylactic ankle
      brace use during a sport season. OBJECTIVE: To determine the effects of
      prophylactic ankle-brace use during a high school basketball season on dynamic
      postural control and functional tests. DESIGN: Prospective repeated-measures
      design. SETTING: High school athletic facility. PARTICIPANTS: 21 healthy high
      school basketball athletes (13 girls, 8 boys). INTERVENTIONS: The order of
      testing was randomized using the Star Excursion Balance Test (SEBT) for
      posteromedial (PM), medial (M), and anteromedial (AM) directions and 3 functional
      tests (FT) consisting of the single-leg crossover hop, single-leg vertical jump,
      and the single-leg 6-m hop for time at pre-, mid-, and postseason. After
      pretesting, the ankle brace was worn on both limbs during the entire 16-wk
      competitive basketball season. MAIN OUTCOME MEASURES: SEBT for PM, M, and AM and
      3 single-leg FTs. RESULTS: Dynamic postural control using the SEBT and the 3 FTs
      improved over time, notably from pretest to posttest. The left limb was different
      from the right limb during the single-leg vertical jump. Effect sizes were large
      for pretest to posttest for the 3 SEBT directions and 2 of the 3 FTs.
      CONCLUSIONS: The 16-wk basketball prophylactic ankle-brace intervention
      significantly improved dynamic postural control and single-limb FTs over time.

PMID- 25559785
TI  - Surgery or radiotherapy for the treatment of bone hydatid disease: a
      retrospective case series.
AB  - BACKGROUND: Currently, there is no accepted treatment for inoperable bone hydatid
      disease where medical treatment has proved ineffective. Alternative treatment
      strategies are therefore urgently needed. Radiotherapy may constitute a treatment
      option, but there is currently a lack of adequate evidence. This study sought to
      retrospectively assess the efficacy and safety of surgery or radiotherapy in the
      treatment of bone hydatid disease in patients attending a single hospital in
      China. METHODS: This was a retrospective case series analyzing clinical data from
      consecutive patients treated between January 2000 and December 2011. Patients
      with an Echinococcus sp infection were counselled about their disease and the
      potential treatment options, and made an informed decision between surgery and
      radiotherapy. All patients were followed up. The treatment outcome was observed
      in the two treatment groups based on the frequencies of relapse and
      complications, and self-evaluated patient satisfaction. RESULTS: Of 40 patients
      (age range 25-57 years), 24 opted for surgery and 16 for radiotherapy. Relapse
      occurred in 14 patients (58%) post-surgery and in three patients (21%) post
      radiotherapy. Bone defects, limb movement disorders, and pain were reported in
      seven patients (29%) post-surgery, while two patients (13%) reported hardening of
      the irradiated region or a limb after radiotherapy. Titres of parasite-specific
      antibodies decreased significantly after radiotherapy but not after surgical
      intervention. Patient satisfaction was significantly higher in the radiotherapy
      group. CONCLUSION: This retrospective case series describes, for the first time,
      the clinical outcomes in a series of patients treated with radiotherapy for bone
      hydatid disease. Although no direct comparison between the treatment groups could
      be made due to methodological limitations of the study design, this study
      indicates that well-designed prospective randomized controlled clinical trials
      assessing radiotherapy may be warranted in patients with inoperable hydatid
      disease of the bones.

PMID- 25559786
TI  - Resilience, stressful life events, and depressive symptomatology among older
      Chinese adults.
AB  - OBJECTIVE: The association between exposure to stressful life events (SLEs) and
      late-life depression is well-documented. However, the role of resilience as a
      buffer against the adverse mental health effects of SLEs in late life has not
      been convincingly demonstrated. In this paper, the moderating effect of
      resilience in the relationship between SLEs and depressive symptomatology in
      older Chinese adults is investigated. METHOD: A population sample of 385
      community-dwelling older Chinese adults aged >=60 years responded to
      questionnaires on resilience (Connor-Davidson resilience scale), depressive
      symptomatology (Geriatric Depression Scale, GDS-15) and SLEs. RESULTS: Increased
      numbers of SLEs (beta = 0.343, p < .001) and lower levels of resilience (beta = 
      0.137, p < 0.001) were significantly associated with higher levels of depressive
      symptomatology. There was a significant interaction of resilience and number of
      SLEs on depressive symptomatology (p = 0.003). The sense of personal competence
      and optimism was the principal underlying resilience dimension moderating the
      relationship for both the young-old (aged 60-69) and the old-old (aged 70 and
      above). CONCLUSION: The finding of significant interaction supported the role of
      resilience in moderating the adverse effect of SLEs in terms of depressive
      symptoms among older Chinese adults.

PMID- 25559787
TI  - Better to give and to compete? Prosocial and competitive motives as interactive
      predictors of citizenship behavior.
AB  - Research has returned mixed results concerning the relationship between prosocial
      motivation and citizenship behavior. Building from research suggesting that mixed
      motives might explain these equivocal findings, we conducted two field studies
      examining the interaction between prosocial and competitive motives and two types
      of citizenship behavior. Prosocial motivation, but not competitive motivation,
      was positively related to citizenship behavior directed at others, though this
      relationship was weakened when prosocial motives were accompanied by competitive
      motives. Prosocial motives compensated for weak competitive motives to predict
      citizenship behavior directed toward the organization. Our studies expand
      research on prosocial and competitive motivation, mixed-motives, and citizenship
      behavior. Further, they carry personnel implications given that many
      organizations seek to hire employees high on both competitive and prosocial
      motivation. 

PMID- 25559789
TI  - Individual sensitivity to occupational hazards.

PMID- 25559791
TI  - Working with asbestos and the possible health risks.
AB  - BACKGROUND: The generic term asbestos refers to a group of crystalline mineral
      silicates that occur naturally in various forms. Because of their properties of
      strength, heat and electrical resistance and their ability to withstand corrosion
      by acids and sea water, asbestos was used extensively both in the UK and
      worldwide. AIMS: To provide a historical perspective of this ubiquitous
      occupational hazard, consider the key changes in UK legislation aimed at
      improving the management of this occupational health risk and describe the
      evidence from the scientific literature concerning asbestos and disease. METHODS:
      Original articles, reviews (including reference textbooks) and scientific
      literature in PubMed and other principal medical science databases, 1960-2014,
      were searched. Publications by regulatory agencies and by governmental
      organizations were also considered and included where relevant. RESULTS: Asbestos
      remains the biggest cause of cancer deaths worldwide. For malignant mesothelioma
      deaths alone, it is estimated that in the UK, between 2015 and 2020, the number
      of cases will peak at 2500 cases annually. It is not clear whether there is a
      safe level of asbestos fibres in air. Evidence for the efficacy of health
      surveillance is lacking. CONCLUSIONS: Although the use of asbestos was banned in
      the UK in 1985 (amosite and crocidolite) and 1999 (chrysotile), it remains a
      significant occupational risk factor for work-related morbidity and mortality,
      causing both benign and malignant diseases, often with long latency. Further
      research is needed regarding exposure levels and health surveillance.

PMID- 25559793
TI  - A memorable patient.

PMID- 25559794
TI  - The art of observation.

PMID- 25559795
TI  - Implementing NICE obesity guidance for staff: an NHS trust audit.
AB  - BACKGROUND: The UK National Institute of Health and Clinical Excellence (NICE)
      has produced guidelines (CG43) on preventing and managing overweight and obesity,
      which apply to the National Health Service (NHS) as an employer. AIMS: To record
      in an NHS trust baseline assessment and management of obesity by its occupational
      health (OH) service staff, with reference to the standards in CG43, enabling
      deficiencies to be identified and improvements to be recommended as a benchmark
      for future measurement. METHODS: Criteria relevant to OH in CG43 were identified
      and data were collected from trust policies, interviews with managers,
      questionnaires to OH staff, examination of OH resources and case notes of staff
      attending OH. Results were checked for compliance with CG43 standards. RESULTS:
      Although the trust met NICE standards as an employer, significant lack of
      compliance was found in its OH service. Only 53% of staff attending medical
      examinations had weight recorded, OH resources were inadequate and 75% of its
      staff had received no training. Problems identified included lack of written
      guidance, time and care pathways. The resulting action plan included a consultant
      led working party liaising with the trust's health and well-being committee,
      training, enhanced OH resources, an obesity protocol, a database and weight
      management clinics. CONCLUSIONS: We found not only a lack of OH policy guidance
      but apparent inertia in dealing with obesity. The action plan demonstrated how OH
      clinical practice can draw upon CG43 to combat obesity in an NHS workforce.

PMID- 25559796
TI  - The Chalder Fatigue Scale (CFQ 11).

PMID- 25559797
TI  - Stress effects on the initial lithiation of crystalline silicon nanowires:
      reactive molecular dynamics simulations using ReaxFF.
AB  - Silicon (Si) has been recognized as a promising anode material for the next
      generation high-capacity lithium (Li)-ion batteries because of its high
      theoretical energy density. Recent in situ transmission electron microscopy (TEM)
      revealed that the electrochemical lithiation of crystalline Si nanowires (c
      SiNWs) proceeds by the migration of the interface between the lithiated Si
      (LixSi) shell and the pristine unlithiated core, accompanied by solid-state
      amorphization. The underlying atomic mechanisms of Li insertion into c-Si remain
      poorly understood. Herein, we perform molecular dynamics (MD) simulations using
      the reactive force field (ReaxFF) to characterize the lithiation process of c
      SiNWs. Our calculations show that ReaxFF can accurately reproduce the energy
      barriers of Li migration from DFT calculations in both crystalline (c-Si) and
      amorphous Si (a-Si). The ReaxFF-based MD simulations reveal that Li insertion
      into interlayer spacing between two adjacent (111) planes results in the peeling
      off of the (111) facets and subsequent amorphization, in agreement with
      experimental observations. We find that breaking of the Si-Si bonds between (111)
      bilayers requires a rather high local Li concentration, which explains the
      atomically sharp amorphous-crystalline interface (ACI). Our stress analysis shows
      that lithiation induces compressive stress at the ACI layer, causing retardation
      or even the stagnation of the reaction front, also in good agreement with TEM
      observations. Lithiation at high temperatures (e.g. 1200 K) shows that Li
      insertion into c-SiNW results in an amorphous to crystalline phase transformation
      at Li : Si composition of ~4.2 : 1. Our modeling results provide a comprehensive
      picture of the effects of reaction and diffusion-induced stress on the
      interfacial dynamics and mechanical degradation of SiNW anodes under chemo
      mechanical lithiation. 

PMID- 25559799
TI  - Refining the Role for Adjuvant Radiotherapy in Gastric Cancer: Risk
      Stratification Is Key.

PMID- 25559798
TI  - Randomized phase II study of carboplatin and paclitaxel with either linifanib or
      placebo for advanced nonsquamous non-small-cell lung cancer.
AB  - PURPOSE: Linifanib, a potent, selective inhibitor of vascular endothelial growth
      factor (VEGF) and platelet-derived growth factor (PDGF) receptors, has single
      agent activity in non-small-cell lung cancer (NSCLC). We evaluated linifanib with
      carboplatin and paclitaxel as first-line therapy of advanced nonsquamous NSCLC.
      PATIENTS AND METHODS: Patients with stage IIIB/IV nonsquamous NSCLC were randomly
      assigned to 3-week cycles of carboplatin (area under the curve 6) and paclitaxel
      (200 mg/m(2)) with daily placebo (arm A), linifanib 7.5 mg (arm B), or linifanib
      12.5 mg (arm C). The primary end point was progression-free survival (PFS);
      secondary efficacy end points included overall survival (OS) and objective
      response rate. RESULTS: One hundred thirty-eight patients were randomly assigned
      (median age, 61 years; 57% men; 84% smokers). Median PFS times were 5.4 months
      (95% CI, 4.2 to 5.7 months) in arm A (n = 47), 8.3 months (95% CI, 4.2 to 10.8
      months) in arm B (n = 44), and 7.3 months (95% CI, 4.6 to 10.8 months) in arm C
      (n = 47). Hazard ratios (HRs) for PFS were 0.51 for arm B versus A (P = .022) and
      0.64 for arm C versus A (P = .118). Median OS times were 11.3, 11.4, and 13.0
      months in arms A, B, and C, respectively. HRs for OS were 1.08 for arm B versus A
      (P = .779) and 0.88 for arm C versus A (P = .650). Both linifanib doses were
      associated with increased toxicity, including a higher incidence of adverse
      events known to be associated with VEGF/PDGF inhibition. Baseline plasma
      carcinoembryonic antigen/cytokeratin 19 fragments biomarker signature was
      associated with PFS improvement and a trend toward OS improvement with linifanib
      12.5 mg. CONCLUSION: Addition of linifanib to chemotherapy significantly improved
      PFS (arm B), with a modest trend for survival benefit (arm C) and increased
      toxicity reflective of known VEGF/PDGF inhibitory effects.

PMID- 25559800
TI  - Concurrent chemoradiotherapy in stage III non-small-cell lung cancer: what is the
      best regimen?

PMID- 25559801
TI  - Ageism in the undertreatment of high-risk prostate cancer: how long will clinical
      practice patterns resist the weight of evidence?

PMID- 25559802
TI  - Never say never.

PMID- 25559803
TI  - Prevalence of cerebral small-vessel disease in long-term breast cancer survivors
      exposed to both adjuvant radiotherapy and chemotherapy.
AB  - PURPOSE: Adjuvant radiotherapy and chemotherapy for breast cancer have been
      related to transient ischemic attacks and stroke. To date, no studies have
      investigated the relationship between these adjuvant therapies and subclinical
      cerebral small-vessel disease in survivors of breast cancer. We compared white
      matter lesion (WML) volume and prevalence of brain infarctions and cerebral
      microbleeds (CMBs) between breast cancer survivors exposed to adjuvant
      radiotherapy and chemotherapy (aRCeBCSs) for primary disease and a population
      based reference group. PATIENTS AND METHODS: Multimodal magnetic resonance
      imaging (1.5 T) was performed in 187 aRCeBCSs who received primary breast cancer
      treatment on average more than 20 years before this study and 374 age-matched
      reference women without a history of cancer. WML volume was segmented using fully
      automated software. Experienced raters reviewed all scans for cortical
      infarctions, lacunar infarctions, strictly lobar CMBs, and deep/infratentorial
      CMBs with or without lobar CMBs. Within the aRCeBCS group, we also analyzed the
      association between relative radiotherapy exposure to the carotid artery and
      prevalence of WML volume and CMBs. RESULTS: The aRCeBCS group had a higher
      prevalence of both total CMBs and CMBs in a deep/infratentorial region than the
      reference group. No between-group differences were observed in the prevalence of
      infarctions or WML volume. Exposure of the carotid artery to radiation was not
      associated with WML volume or CMBs. CONCLUSION: More CMBs were found in the
      aRCeBCS group than in the population-based controls. These vascular lesions
      potentially mark cerebrovascular frailty that could partially explain the well
      documented association between chemotherapy and cognitive dysfunction. No support
      was found for a radiotherapy-related origin of CMBs.

PMID- 25559805
TI  - PIK3CA genotype and treatment decisions in human epidermal growth factor receptor
      2-positive breast cancer.

PMID- 25559804
TI  - Prediction of serious complications in patients with seemingly stable febrile
      neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a
      prospective cohort of patients from the FINITE study.
AB  - PURPOSE: To validate a prognostic score predicting major complications in
      patients with solid tumors and seemingly stable episodes of febrile neutropenia
      (FN). The definition of clinical stability implies the absence of organ
      dysfunction, abnormalities in vital signs, and major infections. PATIENTS AND
      METHODS: We developed the Clinical Index of Stable Febrile Neutropenia (CISNE),
      with six explanatory variables associated with serious complications: Eastern
      Cooperative Oncology Group performance status >= 2 (2 points), chronic
      obstructive pulmonary disease (1 point), chronic cardiovascular disease (1
      point), mucositis of grade >= 2 (National Cancer Institute Common Toxicity
      Criteria; 1 point), monocytes < 200 per MUL (1 point), and stress-induced
      hyperglycemia (2 points). We integrated these factors into a score ranging from 0
      to 8, which classifies patients into three prognostic classes: low (0 points),
      intermediate (1 to 2 points), and high risk (>= 3 points). We present a
      multicenter validation of CISNE. RESULTS: We prospectively recruited 1,133
      patients with seemingly stable FN from 25 hospitals. Complication rates in the
      training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1%
      and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality
      rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3%
      and 3.1% in high-risk patients. Areas under the receiver operating characteristic
      curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott,
      0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care
      in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for
      comparison between CISNE and MASCC). CONCLUSION: CISNE is a valid model for
      accurately classifying patients with cancer with seemingly stable FN episodes.

PMID- 25559806
TI  - Health-related quality of life after colorectal cancer in England: a patient
      reported outcomes study of individuals 12 to 36 months after diagnosis.
AB  - PURPOSE: This population-level study was conducted to define the health-related
      quality of life (HRQL) of individuals living with and beyond colorectal cancer
      (CRC) and to identify factors associated with poor health outcomes. PATIENTS AND
      METHODS: All individuals diagnosed with CRC in England in 2010 and 2011 who were
      alive 12 to 36 months after diagnosis were sent a questionnaire. This included
      questions related to treatment, disease status, other long-term conditions
      (LTCs), generic HRQL (EuroQol-5D), and cancer-specific outcomes (Functional
      Assessment of Cancer Therapy and Social Difficulties Inventory items). RESULTS:
      The response rate was 63.3% (21,802 of 34,467 patients). One or more generic
      health problems were reported by 65% of respondents, with 10% of patients
      reporting problems in all five domains. The reporting of problems was higher than
      in the general population and was most marked in those age less than 55 years.
      Certain subgroups reported a higher number of problems, notably those with one or
      more other LTCs, those with active or recurrent disease, those with a stoma, and
      those at the extremes of the age range (< 55 and > 85 years). Of respondents
      without a stoma, 16.3% reported no bowel control. Reversal of a stoma resulted in
      fewer severe bowel problems but more moderate problems than those who had never
      had a stoma. A quarter of rectal cancer respondents (25.1%) reported difficulties
      with sexual matters (compared with 11.2% of colon cancer respondents).
      CONCLUSION: This study demonstrates the success of a national patient-reported
      outcomes survey. The results have the potential to support system-wide
      improvement in health outcomes through the identification of particular
      challenges faced by individuals after treatment for CRC.

PMID- 25559807
TI  - Anterior hypopituitarism in adult survivors of childhood cancers treated with
      cranial radiotherapy: a report from the St Jude Lifetime Cohort study.
AB  - PURPOSE: To estimate the prevalence of and risk factors for growth hormone
      deficiency (GHD), luteinizing hormone/follicle-stimulating hormone deficiencies
      (LH/FSHD), thyroid-stimulatin hormone deficiency (TSHD), and adrenocorticotropic
      hormone deficiency (ACTHD) after cranial radiotherapy (CRT) in childhood cancer
      survivors (CCS) and assess the impact of untreated deficiencies. PATIENTS AND
      METHODS: Retrospective study in an established cohort of CCS with 748
      participants treated with CRT (394 men; mean age, 34.2 years [range, 19.4 to 59.6
      years] observed for a mean of 27.3 years [range, 10.8 to 47.7 years]).
      Multivariable logistic regression was used to study associations between
      demographic and treatment-related risk factors and pituitary deficiencies, as
      well as associations between untreated deficiencies and cardiovascular health,
      bone mineral density (BMD), and physical fitness. RESULTS: The estimated point
      prevalence was 46.5% for GHD, 10.8% for LH/FSHD, 7.5% for TSHD, and 4% for ACTHD,
      and the cumulative incidence increased with follow-up. GHD and LH/FSHD were not
      treated in 99.7% and 78.5% of affected individuals, respectively. Male sex and
      obesity were significantly associated with LH/FSHD; white race was significant
      associated with LH/FSHD and TSHD. Compared with CRT doses less than 22 Gy, doses
      of 22 to 29.9 Gy were significantly associated with GHD; doses >= 22 Gy were
      associated with LH/FSHD; and doses >= 30 Gy were associated with TSHD and ACTHD.
      Untreated GHD was significantly associated with decreased muscle mass and
      exercise tolerance; untreated LH/FSHD was associated with hypertension,
      dyslipidemia, low BMD, and slow walking; and both deficits, independently, were
      associated with with abdominal obesity, low energy expenditure, and muscle
      weakness. CONCLUSION: Anterior pituitary deficits are common after CRT. Continued
      development over time is noted for GHD and LH/FSHD with possible associations
      between nontreatment of these conditions and poor health outcomes.

PMID- 25559808
TI  - Effectiveness of androgen-deprivation therapy and radiotherapy for older men with
      locally advanced prostate cancer.
AB  - PURPOSE: We examined whether the survival advantage of androgen-deprivation
      therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with
      locally advanced prostate cancer reported in two randomized trials holds in real
      world clinical practice and extended the evidence to patients poorly represented
      in the trials. METHODS: We conducted nonrandomized effectiveness studies of ADT
      plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007
      and observed through 2009 in the SEER-Medicare data set: (1) the randomized
      clinical trial (RCT) cohort, which included men age 65 to 75 years and was most
      consistent with participants in the randomized trials; (2) the elderly cohort,
      which included men age > 75 years with locally advanced prostate cancer; and (3)
      the screen-detected cohort, which included men age >= 65 years with screen
      detected high-risk prostate cancer. We evaluated cause-specific and all-cause
      mortality using propensity score, instrumental variable (IV), and sensitivity
      analyses. RESULTS: In the RCT cohort, ADT plus RT was associated with reduced
      cause-specific and all-cause mortality relative to ADT alone (cause-specific
      propensity score-adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all
      cause propensity score-adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness
      estimates for the RCT cohort were not significantly different from those from
      randomized trials (P > .1). In the elderly and screen-detected cohorts, ADT plus
      RT was also associated with reduced cause-specific and all-cause mortality. IV
      analyses produced estimates similar to those from propensity score-adjusted
      methods. CONCLUSION: Older men with locally advanced or screen-detected high-risk
      prostate cancer who receive ADT alone risk decrements in cause-specific and
      overall survival.

PMID- 25559809
TI  - Genetic diagnosis of high-penetrance susceptibility for colorectal cancer (CRC)
      is achievable for a high proportion of familial CRC by exome sequencing.
AB  - PURPOSE: Knowledge of the contribution of high-penetrance susceptibility to
      familial colorectal cancer (CRC) is relevant to the counseling, treatment, and
      surveillance of CRC patients and families. PATIENTS AND METHODS: To quantify the
      impact of germline mutation to familial CRC, we sequenced the mismatch repair
      genes (MMR) APC, MUTYH, and SMAD4/BMPR1A in 626 early-onset familial CRC cases
      ascertained through a population-based United Kingdom national registry. In
      addition, we evaluated the contribution of mutations in the exonuclease domain
      (exodom) of POLE and POLD1 genes that have recently been reported to confer CRC
      risk. RESULTS: Overall mutations (pathogenic, likely pathogenic) in MMR genes
      make the highest contribution to familial CRC (10.9%). Mutations in the other
      established CRC genes account for 3.3% of cases. POLE/POLD1 exodom mutations were
      identified in three patients with family histories consistent with dominant
      transmission of CRC. Collectively, mutations in the known genes account for 14.2%
      of familial CRC (89 of 626 cases; 95% CI = 11.5, 17.2). CONCLUSION: A genetic
      diagnosis is feasible in a high proportion of familial CRC. Mainstreaming such
      analysis in clinical practice should enable the medical management of patients
      and their families to be optimized. Findings suggest CRC screening of POLE and
      POLD1 mutation carriers should be comparable to that afforded to those at risk of
      HNPCC. Although the risk of CRC associated with unexplained familial CRC is in
      general moderate, in some families the risk is substantive and likely to be the
      consequence of unidentified genes, as exemplified by POLE and POLD1. Our findings
      have utility in the design of genetic analyses to identify such novel CRC risk
      genes.

PMID- 25559810
TI  - Improving selection criteria for early cystectomy in high-grade t1 bladder
      cancer: a meta-analysis of 15,215 patients.
AB  - PURPOSE: High-grade T1 (HGT1) bladder cancer is the highest risk subtype of non
      muscle-invasive bladder cancer, with highly variable prognosis, poorly understood
      risk factors, and considerable debate about the role of early cystectomy. We
      aimed to address these questions through a meta-analysis of outcomes and
      prognostic factors. METHODS: PubMed, EMBASE, Cochrane Central Register of
      Controlled Trials, and American Society of Clinical Oncology abstracts were
      searched for cohort studies in HGT1. We pooled data on recurrence, progression,
      and cancer-specific survival from 73 studies. RESULTS: Five-year rates of
      recurrence, progression, and cancer-specific survival were 42% (95% CI, 39% to
      45%), 21% (95% CI, 18% to 23%), and 87% (95% CI, 85% to 89%), respectively (56
      studies, n = 15,215). In the prognostic factor meta-analysis (33 studies, n =
      8,880), the highest impact risk factor was depth of invasion (T1b/c) into lamina
      propria (progression: hazard ratio [HR], 3.34; P < .001; cancer-specific
      survival: HR, 2.02; P = .001). Several other previously proposed factors also
      predicted progression and cancer-specific survival (lymphovascular invasion,
      associated carcinoma in situ, nonuse of bacillus Calmette-Guerin, tumor size > 3
      cm, and older age; HRs for progression between 1.32 and 2.88, P <= .002; HRs for
      cancer-specific survival between 1.28 and 2.08, P <= .02). CONCLUSION: In this
      large analysis of outcomes and prognostic factors in HGT1 bladder cancer, deep
      lamina propria invasion had the largest negative impact, and other previously
      proposed prognostic factors were also confirmed. These factors should be used for
      prognostication and patient stratification in future clinical trials, and depth
      of invasion should be considered for inclusion in TNM staging criteria. This meta
      analysis can also help define selection criteria for early cystectomy in HGT1
      bladder cancer, particularly for patients with deep lamina propria invasion
      combined with other risk factors.

PMID- 25559811
TI  - Phase III Trial to Compare Adjuvant Chemotherapy With Capecitabine and Cisplatin
      Versus Concurrent Chemoradiotherapy in Gastric Cancer: Final Report of the
      Adjuvant Chemoradiotherapy in Stomach Tumors Trial, Including Survival and Subset
      Analyses.
AB  - PURPOSE: The Adjuvant Chemoradiotherapy in Stomach Tumors (ARTIST) trial tested
      whether the addition of radiotherapy to adjuvant chemotherapy improved disease
      free survival (DFS) in patients with D2-resected gastric cancer (GC). PATIENTS
      AND METHODS: Between November 2004 and April 2008, 458 patients with GC who
      received gastrectomy with D2 lymph node dissection were randomly assigned to
      either six cycles of adjuvant chemotherapy with capecitabine and cisplatin (XP)
      or to two cycles of XP followed by chemoradiotherapy and then two additional
      cycles of XP (XPRT). This final update contains the first publication of overall
      survival (OS), together with updated DFS and subset analyses. RESULTS: With 7
      years of follow-up, DFS remained similar between treatment arms (hazard ratio
      [HR], 0.740; 95% CI, 0.520 to 1.050; P=.0922). OS also was similar (HR, 1.130;
      95% CI, 0.775 to 1.647; P=.5272). The effect of the addition of radiotherapy on
      DFS and OS differed by Lauren classification (interaction P=.04 for DFS;
      interaction P=.03 for OS) and lymph node ratio (interaction P<.01 for DFS;
      interaction P<.01 for OS). Subgroup analyses also showed that chemoradiotherapy
      significantly improved DFS in patients with node-positive disease and with
      intestinal-type GC. There was a similar trend for DFS and OS by stage of disease.
      CONCLUSION: In D2-resected GC, both adjuvant chemotherapy and chemoradiotherapy
      are tolerated and equally beneficial in preventing relapse. Because results
      suggest a significant DFS effect of chemoradiotherapy in subsets of patients, the
      ARTIST 2 trial evaluating adjuvant chemotherapy and chemoradiotherapy in patients
      with node-positive, D2-resected GC is under way.

PMID- 25559812
TI  - Effect of topical vaginal androgens in a woman on the testosterone levels of her
      sexual partner with prostate cancer.

PMID- 25559814
TI  - Next-generation strategies for hereditary colorectal cancer risk assessment.

PMID- 25559813
TI  - Intrinsic subtypes, PIK3CA mutation, and the degree of benefit from adjuvant
      trastuzumab in the NSABP B-31 trial.
AB  - PURPOSE: Considerable molecular heterogeneity exists among human epidermal growth
      factor receptor 2 (HER2) -positive breast cancer regarding gene expression and
      mutation profiling. Evidence from preclinical, clinical neoadjuvant, and
      metastatic clinical trials suggested that PIK3CA mutational status and PAM50
      intrinsic subtype of a tumor were markers of response to anti-HER2 therapies. We
      evaluated the predictive value of these two biomarkers in the adjuvant setting
      using archived tumor blocks from National Surgical Adjuvant Breast and Bowel
      Project (NSABP) trial B-31. PATIENTS AND METHODS: Expression data for 49 genes
      using the nCounter platform were used to generate PAM50 intrinsic subtypes for
      1,578 archived tumor blocks from patients in the B-31 trial. Six PIK3CA hotspot
      mutations were examined by mass spectrometry of the primer extension products in
      a randomly selected subset (n = 671). We examined the heterogeneity of
      trastuzumab treatment effect across different subsets defined by each marker
      using Cox regression and disease-free survival as the end point. RESULTS: Seven
      hundred forty-one (47.0%) of 1,578 tumors were classified as HER2-enriched
      (HER2E) subtype, and 166 (24.7%) of 671 tumors had PIK3CA mutations. Hazard
      ratios (HRs) for trastuzumab in HER2E and other subtypes were 0.44 (95% CI, 0.34
      to 0.58; P < .001) and 0.47 (95% CI, 0.35 to 0.62; P < .001), respectively
      (interaction P = .67). HRs for trastuzumab in PIK3CA wild-type and mutated tumors
      were 0.51 (95% CI, 0.37 to 0.71; P < .001) and 0.44 (95% CI, 0.24 to 0.82; P =
      .009), respectively (interaction P = .64). CONCLUSION: Unlike results seen in the
      metastatic and neoadjuvant clinical trials, PIK3CA and PAM50 intrinsic subtypes
      were not predictive biomarkers for adjuvant trastuzumab in NSABP B-31. These data
      suggest that results from the metastatic and neoadjuvant setting may not be
      always applicable to the adjuvant setting.

PMID- 25559815
TI  - The 42nd David A. Karnofsky Memorial Award Lecture: Understanding.

PMID- 25559816
TI  - Bronchoalveolar lavage and lung biopsy in patients with cancer and hematopoietic
      stem-cell transplantation recipients: a systematic review and meta-analysis.
AB  - PURPOSE: The objective of this study was to describe the diagnostic yield and
      complication rate of bronchoalveolar lavage (BAL) and lung biopsy in the
      evaluation of pulmonary lesions in patients with cancer and recipients of
      hematopoietic stem-cell transplantation (HSCT). METHODS: We conducted a
      systematic literature review and performed electronic searches of Ovid MEDLINE,
      EMBASE, and Cochrane Central Register of Controlled Trials. Studies were included
      if patients had cancer or were recipients of HSCT, and if they underwent BAL or
      lung biopsy for the evaluation of pulmonary lesions. Only English language
      publications were included. RESULTS: In all, 14,148 studies were screened; 72
      studies of BAL and 31 of lung biopsy were included. The proportion of procedures
      leading to any diagnosis was similar by procedure type (0.53 v 0.54; P = .94) but
      an infectious diagnosis was more common with BAL compared with lung biopsy (0.49
      v 0.34; P < .001). Lung biopsy more commonly led to a noninfectious diagnosis
      (0.43 v 0.07; P < .001) and was more likely to change how the patient was managed
      (0.48 v 0.31; P = .002) compared with BAL. However, complications were more
      common with lung biopsy (0.15 v 0.08; P = .006), and procedure-related mortality
      was four-fold higher for lung biopsy (0.0078) compared with BAL (0.0018).
      CONCLUSION: BAL may be the preferred diagnostic modality for the evaluation of
      potentially infectious pulmonary lesions because of lower complication and
      mortality rates; thus, choice of procedure depends on clinical suspicion of
      infection. Guidelines to promote consistency in the approach to the evaluation of
      lung infiltrates may improve clinical care of patients.

PMID- 25559817
TI  - Tumor-infiltrating lymphocytes and response to platinum in triple-negative breast
      cancer.

PMID- 25559818
TI  - PIK3CA mutations are associated with decreased benefit to neoadjuvant human
      epidermal growth factor receptor 2-targeted therapies in breast cancer.
AB  - PURPOSE: We investigated whether mutations in the gene encoding the
      phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with
      response to neoadjuvant human epidermal growth factor receptor 2 (HER2) -targeted
      therapies in patients with breast cancer. PATIENTS AND METHODS: Baseline tissue
      biopsies were available from patients with HER2-positive early breast cancer who
      were enrolled onto the Neoadjuvant Lapatinib and/or Trastuzumab Treatment
      Optimization trial (NeoALTTO). Activating mutations in PIK3CA were identified
      using mass spectrometry-based genotyping. RESULTS: PIK3CA mutations were
      identified in 23% of HER2-positive breast tumors, and these mutations were
      associated with poorer outcome in all of the treatment arms. Patients treated
      with a combination of trastuzumab and lapatinib who had wild-type PIK3CA obtained
      a total pathologic complete response (pCR) rate of 53.1%, which decreased to
      28.6% in patients with tumors that carried PIK3CA activating mutations (P =
      .012). CONCLUSION: Activating mutations in PIK3CA predicted poor pCR in patients
      with HER2-positive breast cancer treated with neoadjuvant therapies that target
      HER2. Consequently, the combination of anti-HER2 agents and PI3K inhibitors is
      being investigated.

PMID- 25559819
TI  - Bone marrow minimal residual disease was an early response marker and a
      consistent independent predictor of survival after anti-GD2 immunotherapy.
AB  - PURPOSE: Immunotherapy is a standard of care for children with high-risk
      neuroblastoma, where bone marrow (BM) is the predominant metastatic site. Early
      response markers of minimal residual disease (MRD) in the BM that are also
      predictive of survival could help individualize patient therapies. PATIENTS AND
      METHODS: After achieving first remission (n = 163), primary refractory disease (n
      = 102), or second remission (n = 95), children with stage 4 neuroblastoma
      received anti-GD2 3F8 antibody immunotherapy. BM MRD before 3F8 treatment and
      after cycle 2 (postMRD) was measured using a four-marker panel (B4GALNT1, PHOX2B,
      CCND1, and ISL1) by quantitative reverse transcription polymerase chain reaction.
      Progression-free survival (PFS) and overall survival (OS) were estimated using
      the Kaplan-Meier method. Prognostic variables were tested in both univariable and
      multivariable analyses, and MRD markers were further assessed individually and in
      combination as binary composite (postMRD: 0 and 1) and as equal sum (postMRDSum:
      0 to 4) using the Cox regression models, and their predictive accuracy was
      determined by the concordance index. RESULTS: When BM was evaluated after cycle
      2, individual markers were highly predictive of PFS and OS. The prediction
      accuracy improved when they were combined in postMRDSum. A multivariable model
      taking into account all the variables significant in the univariable analyses
      identified postMRDSum to be independently predictive of PFS and OS. When the
      model for OS also included missing killer immunoglobulin-like receptor ligand,
      human antimouse antibody response, and the enrollment disease status, the
      concordance index was 0.704. CONCLUSION: BM MRD after two cycles of immunotherapy
      was confirmed as an early response marker and a consistent independent predictor
      of survival.

PMID- 25559820
TI  - Alterations in siRNA and miRNA expression profiles detected by deep sequencing of
      transgenic rice with siRNA-mediated viral resistance.
AB  - RNA-mediated gene silencing has been demonstrated to serve as a defensive
      mechanism against viral pathogens by plants. It is known that specifically
      expressed endogenous siRNAs and miRNAs are involved in the self-defense process
      during viral infection. However, research has been rarely devoted to the
      endogenous siRNA and miRNA expression changes under viral infection if the
      resistance has already been genetically engineered in plants. Aiming to gain a
      deeper understanding of the RNA-mediated gene silencing defense process in
      plants, the expression profiles of siRNAs and miRNAs before and after viral
      infection in both wild type and transgenic anti-Rice stripe virus (RSV) rice
      plants were examined by small RNA high-throughput sequencing. Our research
      confirms that the newly generated siRNAs, which are derived from the engineered
      inverted repeat construct, is the major contributor of the viral resistance in
      rice. Further analysis suggests the accuracy of siRNA biogenesis might be
      affected when siRNAs machinery is excessively used in the transgenic plants. In
      addition, the expression levels of many known miRNAs are dramatically changed due
      to RSV infection on both wild type and transgenic rice plants, indicating
      potential function of those miRNAs involved in plant-virus interacting process. 

PMID- 25559822
TI  - 2013 Annual Report of the American Association of Poison Control Centers'
      National Poison Data System (NPDS): 31st Annual Report.
AB  - BACKGROUND: This is the 31st Annual Report of the American Association of Poison
      Control Centers' (AAPCC) National Poison Data System (NPDS). As of January 1,
      2013, 57 of the nation's poison centers (PCs) uploaded case data automatically to
      NPDS. The upload interval was 8.08 [7.10, 11.63] (median [25%, 75%]) minutes,
      creating a near real-time national exposure and information database and
      surveillance system. METHODOLOGY: We analyzed the case data tabulating specific
      indices from NPDS. The methodology was similar to that of previous years. Where
      changes were introduced, the differences are identified. Poison center (PC) cases
      with medical outcomes of death were evaluated by a team of 38 medical and
      clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the
      Relative Contribution to Fatality (RCF) of the exposure to the death. RESULTS: In
      2013, 3,060,122 closed encounters were logged by NPDS: 2,188,013 human exposures,
      59,496 animal exposures, 806,347 information calls, 6,116 human-confirmed
      nonexposures, and 150 animal-confirmed nonexposures. Total encounters showed a
      9.3% decline from 2012, while health care facility human exposure calls were
      essentially flat, decreasing by 0.1%.All information calls decreased 21.4% and
      health care facility (HCF) information calls decreased 8.5%, medication
      identification requests (drug ID) decreased 26.8%, and human exposures reported
      to US PCs decreased 3.8%. Human exposures with less serious outcomes have
      decreased 3.7% per year since 2008 while those with more serious outcomes
      (moderate, major or death) have increased by 4.7% per year since 2000. The top
      five substance classes most frequently involved in all human exposures were
      analgesics (11.5%), cosmetics/personal care products (7.7%), household cleaning
      substances (7.6%), sedatives/hypnotics/antipsychotics (5.9%), and antidepressants
      (4.2%). Sedative/hypnotics/antipsychotics exposures as a class increased most
      rapidly (2,559 calls/year) over the last 13 years for cases showing more serious
      outcomes. The top five most common exposures in children of 5 years or less were
      cosmetics/personal care products (13.8%), household cleaning substances (10.4%),
      analgesics (9.8%), foreign bodies/toys/miscellaneous (6.9%), and topical
      preparations (6.1%). Drug identification requests comprised 50.7% of all
      information calls. NPDS documented 2,477 human exposures resulting in death with
      2,113 human fatalities judged related (RCF of 1, undoubtedly responsible; 2,
      probably responsible; or 3, contributory). CONCLUSIONS: These data support the
      continued value of PC expertise and need for specialized medical toxicology
      information to manage the more severe exposures, despite a decrease in calls
      involving less severe exposures. Unintentional and intentional exposures continue
      to be a significant cause of morbidity and mortality in the United States. The
      near real-time, always current status of NPDS represents a national public health
      resource to collect and monitor US exposure cases and information calls. The
      continuing mission of NPDS is to provide a nationwide infrastructure for public
      health surveillance for all types of exposures, public health event
      identification, resilience response and situational awareness tracking. NPDS is a
      model system for the nation and global public health.

PMID- 25559821
TI  - Structural insight into equine lentivirus receptor 1.
AB  - Equine lentivirus receptor 1 (ELR1) has been identified as a functional cellular
      receptor for equine infectious anemia virus (EIAV). Herein, recombinant ELR1 and
      EIAV surface glycoprotein gp90 were respectively expressed in Drosophila
      melanogaster S2 cells, and purified to homogeneity by Ni-NTA affinity
      chromatography and gel filtration chromatography. Gel filtration chromatography
      and analytical ultracentrifugation (AUC) analyses indicated that both ELR1 and
      gp90 existed as individual monomers in solution and formed a complex with a
      stoichiometry of 1:1 when mixed. The structure of ELR1 was first determined with
      the molecular replacement method, which belongs to the space group P42 21 2 with
      one molecule in an asymmetric unit. It contains eight antiparallel beta-sheets,
      of which four are in cysteine rich domain 1 (CRD1) and two are in CRD2 and CRD3,
      respectively. Alignment of ELR1 with HVEM and CD134 indicated that Tyr61, Leu70,
      and Gly72 in CRD1 of ELR1 are important residues for binding to gp90. Isothermal
      titration calorimetry (ITC) experiments further confirmed that Leu70 and Gly72
      are the critical residues. 

PMID- 25559823
TI  - Acid diffusion into rice boluses is influenced by rice type, variety, and
      presence of alpha-amylase.
AB  - Breakdown of rice during gastric digestion may be influenced by rice structure,
      presence of salivary alpha-amylase, and hydrolysis by gastric acid. During
      mastication, saliva is mixed with rice, allowing alpha-amylase to begin starch
      hydrolysis. This hydrolysis may continue in the gastric environment depending on
      the rate at which gastric acid penetrates into the rice bolus. The objective of
      this study was to determine the acid uptake into rice boluses with and without
      alpha-amylase in saliva. Two types each of brown and white rice (medium and long
      grain), were formed into a cylindrical-shaped bolus. Each bolus was sealed on all
      sides except one to allow one-dimensional mass transfer, and incubated by
      immersion in simulated gastric juice at 37  degrees C under static conditions.
      Acidity of the boluses was measured by titration after 1 to 96 h of incubation.
      Effective diffusivity of the gastric juice through the bolus was estimated using
      MATLAB. Average acidity values ranged from 0.04 mg HCl/g dry matter (medium grain
      white rice, no incubation) to 10.01 mg HCl/g dry matter (long-grain brown rice,
      72 h incubation). The rice type, presence of alpha-amylase, and incubation time
      all significantly influenced rice bolus acidity (P < 0.001). Effective
      diffusivity of gastric juice into the bolus was greater in brown rice than in
      white rice. These results indicate that starch hydrolysis by alpha-amylase may
      continue in the stomach before the gastric acid penetrates the rice bolus, and
      the rate of acid uptake will depend on the type of rice consumed. 

PMID- 25559825
TI  - Contemporary challenges in the management of advanced heart failure.

PMID- 25559824
TI  - Effect of human bone marrow mesenchymal stromal cells on cytokine production by
      peripheral blood naive, memory, and effector T cells.
AB  - INTRODUCTION: The different distribution of T cells among
      activation/differentiation stages in immune disorders may condition the outcome
      of mesenchymal stromal cell (MSC)-based therapies. Indeed, the effect of MSCs in
      the different functional compartments of T cells is not completely elucidated.
      METHODS: We investigated the effect of human bone marrow MSCs on naturally
      occurring peripheral blood functional compartments of CD4(+) and CD8(+) T cells:
      naive, central memory, effector memory, and effector compartments. For that,
      mononuclear cells (MNCs) stimulated with phorbol myristate acetate (PMA) plus
      ionomycin were cultured in the absence/presence of MSCs. The percentage of cells
      expressing tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFNgamma),
      and interleukin-2 (IL-2), IL-17, IL-9, and IL-6 and the amount of cytokine
      produced were assessed by flow cytometry. mRNA levels of IL-4, IL-10,
      transforming growth factor-beta (TGF-beta), and cytotoxic T-lymphocyte-associated
      protein 4 (CTLA4) in purified CD4(+) and CD8(+) T cells, and phenotypic and mRNA
      expression changes induced by PMA + ionomycin stimulation in MSCs, were also
      evaluated. RESULTS: MSCs induced the reduction of the percentage of CD4(+) and
      CD8(+) T cells producing TNF-alpha, IFNgamma, and IL-2 in all functional
      compartments, except for naive IFNgamma(+)CD4(+) T cells. This inhibitory effect
      differentially affected CD4(+) and CD8(+) T cells as well as the T-cell
      functional compartments; remarkably, different cytokines showed distinct patterns
      of inhibition regarding both the percentage of producing cells and the amount of
      cytokine produced. Likewise, the percentages of IL-17(+), IL-17(+)TNF-alpha(+),
      and IL-9(+) within CD4(+) and CD8(+) T cells and of IL-6(+)CD4(+) T cells were
      decreased in MNC-MSC co-cultures. MSCs decreased IL-10 and increased IL-4 mRNA
      expression in stimulated CD4(+) and CD8(+) T cells, whereas TGF-beta was reduced
      in CD8(+) and augmented in CD4(+) T cells, with no changes for CTLA4. Finally,
      PMA + ionomycin stimulation did not induce significant alterations on MSCs
      phenotype but did increase indoleamine-2,3-dioxygenase (IDO), inducible
      costimulatory ligand (ICOSL), IL-1beta, IL-8, and TNF-alpha mRNA expression.
      CONCLUSIONS: Overall, our study showed that MSCs differentially regulate the
      functional compartments of CD4(+) and CD8(+) T cells, which may differentially
      impact their therapeutic effect in immune disorders. Furthermore, the influence
      of MSCs on IL-9 expression can open new possibilities for MSC-based therapy in
      allergic diseases.

PMID- 25559826
TI  - Pretransplant and perioperative predictors of early heart transplantation
      outcomes.
AB  - Aim. To identify predictors of 3-month mortality after heart transplantation in a
      Croatian academic center. Methods. A retrospective review of institutional
      database identified 117 heart transplantations from January 2008 to July 2014.
      Two children <14 years were excluded from the study. The remaining 115 patients
      were dichotomized into survivors and non-survivors adjudicated at 3-months
      postoperatively, and their demographic, clinical, and longitudinal hemodynamic
      data were analyzed. Results. 3-month survival after heart transplantation was
      86%. Non-survivors were older (59+/-8 vs 50+/-14 years, P=0.009), more likely to
      have previous cardiac surgery (44% vs 19%; odds ratio [OR] 3.28, 95% confidence
      interval [CI] 1.08-9.90; P=0.029), lower body mass index (BMI) (25+/-4 vs 28+/-2
      kg/m(2), P=0.001), and be diabetics (44% vs 23%; OR 2.57, 95% CI 0.86-7.66;
      P=0.083). Creatinine clearance was marginally superior among survivors (59=19 vs
      48 +/- 20 mL/min, P=0.059). Donor age and sex did not affect outcomes. Non
      survivors were more likely to have had ischemic cardiomyopathy (69% vs 32%,
      P=0.010). Postoperative utilization of epinephrine as a second line inotropic
      agent was a strong predictor of mortality (63% vs 7%; OR 21.91; 95% CI 6.15
      78.06; P<0.001). Serum lactate concentrations were consistently higher among non
      survivors, with the difference being most pronounced 2 hours after
      cardiopulmonary bypass (9.8+/-3.5 vs 5.2+/-3.2 mmol/L, P<0.001). The donor hearts
      exhibited inferior early hemodynamics in non-survivors (cardiac index 3.0+/-1.0
      vs 4.0+/-1.1 L/min/m(2), P=0.001), stroke volume (49+/-24 vs 59+/-19 mL,
      P=0.063), and left and right ventricular stroke work indices (18+/-8 vs 30+/-11
      g/beat/m(2), P<0.001 and 5+/-3 vs 7+/-4 g/beat/m(2), P=0.060, respectively). Non
      survivors were more likely to require postoperative re-sternotomy (50% vs 12%; OR
      7.25, 95% CI 2.29-22.92; P<0.001), renal replacement therapy (RRT) (69% vs 9%; OR
      22.00, 95% CI 6.24-77.54; P<0.001), and mechanical circulatory assistance (MCS)
      (44% vs 5%; OR 14.62, 95% CI 3.84-55.62; P<0.001). Binary logistic regression
      revealed recipient age (P=0.024), serum lactates 2 hours after CPB (P=0.007), and
      epinephrine use on postoperative day 1 (P=0.007) to be independently associated
      with 3-month mortality. Conclusion. Pretransplant predictors of adverse outcome
      after heart transplantation were recipient age, lower BMI, ischemic
      cardiomyopathy, reoperation and diabetes. Postoperative predictors of mortality
      were inferior donor heart hemodynamics, epinephrine use, and serum lactate
      concentrations. Non-survivors were more likely to require re-sternotomy, MCS, and
      RRT.

PMID- 25559828
TI  - Current state-of-the-art of device therapy for advanced heart failure.
AB  - Heart failure remains one of the most common causes of morbidity and mortality
      worldwide. The advent of mechanical circulatory support devices has allowed
      significant improvements in patient survival and quality of life for those with
      advanced or end-stage heart failure. We provide a general overview of past and
      current mechanical circulatory support devices encompassing options for both
      short- and long-term ventricular support. 

PMID- 25559827
TI  - Cardiac allograft vasculopathy: diagnosis, therapy, and prognosis.
AB  - Development of cardiac allograft vasculopathy represents the major determinant of
      long-term survival in patients after heart transplantation. Due to graft
      denervation, these patients seldom present with classic symptoms of angina
      pectoris, and the first clinical presentations are progressive heart failure or
      sudden cardiac death. Although coronary angiography remains the routine technique
      for coronary artery disease detection, it is not sensitive enough for screening
      purposes. This is especially the case in the first year after transplantation
      when diffuse and concentric vascular changes can be easily detected only by
      intravascular ultrasound. The treatment of the established vasculopathy is
      disappointing, so the primary effort should be directed toward early prevention
      and diagnosis. Due to diffuse vascular changes, revascularization procedures are
      restricted only to a relatively small proportion of patients with favorable
      coronary anatomy. Percutaneous coronary intervention is preferred over surgical
      revascularization since it leads to better acute results and patient survival.
      Although there is no proven long-term advantage of drug-eluting stents for the
      treatment of in-stent restenosis, they are preferred over bare-metal stents.
      Severe vasculopathy has a poor prognosis and the only definitive treatment is
      retransplantation. This article reviews the present knowledge on the
      pathogenesis, diagnosis, treatment, and prognosis of cardiac allograft
      vasculopathy.

PMID- 25559829
TI  - Predictors of right ventricular failure after left ventricular assist device
      implantation.
AB  - Number of left ventricular assist device (LVAD) implantations increases every
      year, particularly LVADs for destination therapy (DT). Right ventricular failure
      (RVF) has been recognized as a serious complication of LVAD implantation.
      Reported incidence of RVF after LVAD ranges from 6% to 44%, varying mostly due to
      differences in RVF definition, different types of LVADs, and differences in
      patient populations included in studies. RVF complicating LVAD implantation is
      associated with worse postoperative mortality and morbidity including worse end
      organ function, longer hospital length of stay, and lower success of bridge to
      transplant (BTT) therapy. Importance of RVF and its predictors in a setting of
      LVAD implantation has been recognized early, as evidenced by abundant number of
      attempts to identify independent risk factors and develop RVF predictor scores
      with a common purpose to improve patient selection and outcomes by recognizing
      potential need for biventricular assist device (BiVAD) at the time of LVAD
      implantation. The aim of this article is to review and summarize current body of
      knowledge on risk factors and prediction scores of RVF after LVAD implantation.
      Despite abundance of studies and proposed risk scores for RVF following LVAD,
      certain common limitations make their implementation and clinical usefulness
      questionable. Regardless, value of these studies lies in providing information on
      potential key predictors for RVF that can be taken into account in clinical
      decision making. Further investigation of current predictors and existing scores
      as well as new studies involving larger patient populations and more
      sophisticated statistical prediction models are necessary. Additionally, a short
      description of our empirical institutional approach to management of RVF
      following LVAD implantation is provided.

PMID- 25559830
TI  - Ventricular assist device selection: which one and when?
AB  - Advances in mechanical circulatory support have significantly expanded the
      treatment options for patients with heart failure, whether acute or chronic.
      There are numerous devices available that offer patients short-, intermediate-,
      and long-term duration of support depending on their clinical needs and cardiac
      recovery. Each device has its own technical considerations and the decision which
      device to use depends on several factors, including what is available, the degree
      of support required, and expected duration of support. Additional issues that
      need to be considered in choosing level of support include right heart function,
      respiratory failure, and multi-organ derangements. A widespread availability of
      short-term ventricular assist devices and timely institution for effective
      hemodynamic support will translate into improved patient outcomes whether that is
      successful transfer to a tertiary care facility or recovery of inherent cardiac
      function. Implantable ventricular assist devices have and will continue to evolve
      into smaller and more durable devices, and the future for patients with advanced
      heart failure looks ever-more promising. 

PMID- 25559831
TI  - Results of extracorporeal life support implementation in routine clinical
      practice: single center experience.
AB  - AIM: To describe our experience in the clinical application of extracorporeal
      life support (ECLS) and analyze whether ECLS leads to acceptable clinical
      outcomes in patients with cardiac failure. METHODS: Data from clinical database
      of University Hospital Center Zagreb, Croatia, on 75 patients undergoing ECLS
      support from 2009 to 2014 due to cardiac failure were retrospectively analyzed.
      Outcomes were defined as procedural and clinical outcomes. ECLS as a primary
      procedure and ECLS as a postcardiotomy procedure due to inability to wean from
      cardiopulmonary bypass were analyzed. RESULTS: ECLS was used in 75 adult
      patients, and in 24 (32%) of those procedural success was noted. ECLS was
      implemented as a primary procedure in 36 patients and as a postcardiotomy
      procedure in 39 patients. Nine out of 39 (23.08%) patients had postcardiotomy
      ECLS after heart transplantation. Bleeding complications occurred in 30 (40%)
      patients, both in primary (11/36 patients) and postcardiotomy group (19/39
      patients). ECLS was established by peripheral approach in 46 patients and by
      central cannulation in 27 patients. In 2 patients, combined cannulation was
      performed, with an inflow cannula placed into the right atrium and an outflow
      cannula placed into the femoral artery. Eleven patients treated with peripheral
      approach had ischemic complications. CONCLUSION: ECLS is a useful tool in the
      treatment of patients with refractory cardiac failure and its results are
      encouraging in patients who otherwise have an unfavorable prognosis. Patient
      outcomes may be further improved by technological advances, more clinical
      experience in application of the technique, careful patient selection, and
      multidisciplinary approach in patient management.

PMID- 25559832
TI  - Why pulsatility still matters: a review of current knowledge.
AB  - Continuous-flow left ventricular assist devices (LVAD) have become standard
      therapy option for patients with advanced heart failure. They offer several
      advantages over previously used pulsatile-flow LVADs, including improved
      durability, less surgical trauma, higher energy efficiency, and lower
      thrombogenicity. These benefits translate into better survival, lower frequency
      of adverse events, improved quality of life, and higher functional capacity of
      patients. However, mounting evidence shows unanticipated consequences of
      continuous-flow support, such as acquired aortic valve insufficiency and acquired
      von Willebrand syndrome. In this review article we discuss current evidence on
      differences between continuous and pulsatile mechanical circulatory support, with
      a focus on clinical implications and potential benefits of pulsatile flow.

PMID- 25559833
TI  - Antithrombotics in heart failure.
AB  - Heart failure is a common clinical condition associated with high morbidity and
      mortality rate despite significant improvements in pharmacotherapy and
      implementation of medical procedures. Patients with heart failure are at an
      increased risk of developing arterial and venous thrombosis, which contribute to
      the high rate of adverse events and fatal outcomes. Many heart failure patients
      routinely receive antithrombotic therapy due to the presence of a specific
      indication for its use, like ischemic heart disease or atrial fibrillation.
      However, there is no solid evidence to support the routine use of antithrombotic
      agents in all heart failure patients. This article reviews the evidence for using
      antithrombotic therapy in heart failure patients.

PMID- 25559834
TI  - Antiinflammatory effect of sevoflurane in open lung surgery with one-lung
      ventilation.
AB  - AIM: To prospectively assess the antiinflammatory effect of volatile anesthetic
      sevoflurane in patients undergoing open lung surgery with one lung ventilation
      (OLV). METHODS: This prospective, randomized study included 40 patients
      undergoing thoracic surgery with OLV (NCT02188407). The patients were randomly
      allocated into two equal groups that received either propofol or sevoflurane.
      Four patients were excluded from the study because after surgery they received
      blood transfusion or non-steroid antiinflammatory drugs. Inflammatory mediators
      (interleukins 6, 8, and 10, C-reactive protein [CRP], and procalcitonin) were
      measured perioperatively. The infiltration of the nonoperated lung was assessed
      on chest x-rays and the oxygenation index was calculated. The major postoperative
      complications were counted. RESULTS: Interleukin 6 levels were significantly
      higher in propofol than in sevoflurane group (P=0.014). Preoperative CRP levels
      did not differ between the groups (P=0.351) and in all patients they were lower
      than 20 mg/L, but postoperative CRP was significantly higher in propofol group
      (31+/-6 vs 15+/-7 ng/L; P=0.035); Pre- and postoperative procalcitonin was within
      the reference range (<0.04 ug/L) in both groups. The oxygenation index was
      significantly lower in propofol group (339+/-139 vs 465+/-140; P=0.021). There
      was no significant difference between the groups in lung infiltrates (P=0.5849).
      The number of postoperative adverse events was higher in propofol group, but the
      difference was not-significant (5 vs 1; P=0.115). CONCLUSION: The study suggests
      an antiinflammatory effect of sevoflurane in patients undergoing thoracotomy with
      OLV.

PMID- 25559835
TI  - Genetic polymorphisms in inflammatory response genes and their associations with
      breast cancer risk.
AB  - AIM: To explore the association of NFKB1 c.-798_-795delATTG (rs28362491), NFKBIA
      c.-949C>T (rs2233406), IL-8 c.-352A>T (rs4073), IL-10 c.-854T>C (rs1800871), TNF
      c.-418G>A (rs361525), and TNF c.-488G>A (rs1800629) polymorphisms with breast
      cancer risk in an East Chinese population. METHODS: We conducted a case-control
      study including 975 study participants (474 breast cancer patients and 501 female
      controls without cancer) and genotyped the polymorphisms employing polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic
      regression was used to assess the association of the polymorphisms with breast
      cancer risk. RESULTS: We found that the ins/del and del/del genotypes of NFKB1
      polymorphism and TT genotype of IL-10 polymorphism significantly increased breast
      cancer risk (NFKB1 ins/del odds ratio [OR] 1.69, 95% [CI] 1.23-2.33, P=0.001;
      NFKB1 del/del OR 2.42, 95% CI 1.72-3.42, P<0.001; IL-10 TT OR 2.36, 95% CI 1.58
      3.52, P<0.001). On the other hand, the TT genotype of IL-8 polymorphism, GA and
      AA genotypes of TNF c.-418G>A polymorphism, and GA genotype of TNF c.-488G>A
      polymorphism significantly reduced breast cancer risk (IL-8 TT OR 0.48, 95% CI
      0.33-0.72, P<0.001; TNF c.-418 GA OR 0.58, 95% CI 0.41-0.80, P=0.001; TNF c.-418
      AA OR 0.38, 95% CI 0.14-0.98, P=0.044; TNF c.-488 GA OR 0.68, 95% CI 0.48-0.96,
      P=0.029). When stratified by menopausal status, the CT genotype of NFKBIA
      polymorphism significantly reduced the risk among pre-menopausal women (OR 0.63,
      95% CI 0.40-0.99, P=,043), but not among post-menopausal women. CONCLUSIONS:
      NFKB1, NFKBIA, IL-8, IL-10, and TNF polymorphisms could serve as useful
      predictive biomarkers for breast cancer risk among women in East China.

PMID- 25559837
TI  - An evaluation of direct PCR amplification.
AB  - AIM: To generate complete DNA profiles from blood and saliva samples deposited on
      FTA(r) and non-FTA(r) paper substrates following a direct amplification protocol.
      METHODS: Saliva samples from living donors and blood samples from deceased
      individuals were deposited on ten different FTA(r) and non-FTA(r) substrates.
      These ten paper substrates containing body fluids were kept at room temperature
      for varying lengths of time ranging from one day to approximately one year. For
      all assays in this research, 1.2 mm punches were collected from each substrate
      containing one type of body fluid and amplified with reagents provided in the
      nine commercial polymerase chain reaction (PCR) amplification kits. The
      substrates were not subjected to purification reagent or extraction buffer prior
      to amplification. RESULTS: Success rates were calculated for all nine
      amplification kits and all ten substrates based on their ability to yield
      complete DNA profiles following a direct amplification protocol. Six out of the
      nine amplification kits, and four out of the ten paper substrates had the highest
      success rates overall. CONCLUSION: The data show that it is possible to generate
      complete DNA profiles following a direct amplification protocol using both
      standard (non-direct) and direct PCR amplification kits. The generation of
      complete DNA profiles appears to depend more on the success of the amplification
      kit rather than the than the FTA(r)- or non-FTA(r)-based substrates.

PMID- 25559836
TI  - North vs south differences in acute peptic ulcer hemorrhage in Croatia:
      hospitalization incidence trends, clinical features, and 30-day case fatality.
AB  - AIM: To assess the seven-year trends of hospitalization incidence due to acute
      peptic ulcer hemorrhage (APUH) and associated risk factors, and examine the
      differences in these trends between two regions in Croatia. METHODS: The study
      collected sociodemographic, clinical, and endoscopic data on 2204 patients with
      endoscopically confirmed APUH who were admitted to the Clinical Hospital Center
      "Sestre Milosrdnice," Zagreb and Clinical Hospital Center Split between January
      1, 2005 and December 31, 2011. We determined hospitalization incidence rates, 30
      day case fatality rate, clinical outcomes, and incidence-associated factors.
      RESULTS: No differences were observed in APUH hospitalization incidence rates
      between the regions. Age-standardized one-year cumulative APUH hospitalization
      incidence rate calculated using the European Standard Population was
      significantly higher in Zagreb than in Split region (43.2/100 000 vs
      29.2/100,000). A significantly higher APUH hospitalization incidence rates were
      observed in the above 65 years age group. Overall 30-day case fatality rate was
      4.9%. CONCLUSION: The hospitalization incidence of APUH in two populations did
      not change over the observational period and it was significantly higher in the
      Zagreb region. The incidence of acute duodenal ulcer hemorrhage also remained
      unchanged, whereas the incidence of acute gastric ulcer hemorrhage increased. The
      results of this study allow us to monitor epidemiological indicators of APUH and
      compare data with other countries.

PMID- 25559838
TI  - Establishment of galenic laboratories in developing countries to produce high
      quality medicines: results of Aid Progress Pharmacist Agreement (A.P.P.A.(r))
      Project.

PMID- 25559839
TI  - What is a human embryo? A new piece in the bioethics puzzle.

PMID- 25559840
TI  - Educating science editors: is there a comprehensive strategy?
AB  - The article considers available options to educate science editors in the fast
      transforming digital environment. There is no single course or resource that can
      cover their constantly changing and diversifying educational needs. The
      involvement in research, writing, and reviewing is important for gaining editing
      skills, but that is not all. Membership in editorial associations and access to
      updated scholarly information in the field are mandatory for maintaining
      editorial credentials. Learned associations offer access to a few widely
      recognized periodicals. There are also formal training courses covering issues in
      science writing and ethical editing, but no high-level evidence data exist to
      promote any of these. Networking with like-minded specialists within the global
      and regional editorial associations seems a useful strategy to upgrade editorial
      skills and resolve problems with the quality control and digitization of
      scholarly periodicals. 

PMID- 25559841
TI  - Isolation and transplantation of sturgeon early-stage germ cells.
AB  - We report, for the first time, a series of baseline techniques comprising
      isolation and transplantation of female and male early-stage germ cells in
      sturgeon to generate a germline chimera as a potential tool for surrogate
      reproduction and gene banking. Cells were dissociated from testis, characterized
      by mostly spermatogonia, and from ovary, exclusively comprising oogonia and
      previtellogenic oocytes, of Acipenser baerii, using 0.3% trypsin (2 hours, 23 
      degrees C) dissolved in PBS, isotonic with blood plasma. The dissociated germ
      cells were sorted by Percoll gradient centrifugation followed by immunolabeling
      with germ cell-specific vasa antibody DDX4, while 10% to 30% Percoll solution
      contained 79.4% and 70.8% labeled testicular and ovarian cells. Sorted germ cells
      were transplanted into a cavity close to a presumptive genital ridge of newly
      hatched heterospecific Acipenser ruthenus larvae with fluorescein isothiocyanate
      labeled endogenous primordial germ cells. The transplanted germ cells were
      randomly distributed in the body cavity through 30-day posttransplantation (dpt).
      Subsequently, the cells were organized into genital ridges 50 dpt and
      proliferated 90 dpt. The number of both transplanted and endogenous germ cells
      significantly increased from 18.1, 22.2, and 29.1 (30 dpt) to 108.5, 90.8, and
      118.5 (90 dpt) in ovarian, testicular, and endogenous germ cells, respectively (P
      < 0.05). The efficiency of transplantation was 60% (counted 90 dpt). 

PMID- 25559842
TI  - Flow cytometric method for measuring chromatin fragmentation in fixed sperm from
      yellow perch (Perca flavescens).
AB  - Declining harvests of yellow perch, Perca flavescens, in urbanized watersheds of
      Chesapeake Bay have prompted investigations of their reproductive fitness. The
      purpose of this study was to establish a flow cytometric technique for DNA
      analysis of fixed samples sent from the field to provide reliable gamete quality
      measurements. Similar to the sperm chromatin structure assay, measures were made
      on the susceptibility of nuclear DNA to acid-induced denaturation, but used fixed
      rather than live or thawed cells. Nuclei were best exposed to the acid treatment
      for 1 minute at 37  degrees C followed by the addition of cold (4  degrees C)
      propidium iodide staining solution before flow cytometry. The rationale for
      protocol development is presented graphically through cytograms. Field results
      collected in 2008 and 2009 revealed DNA fragmentation up to 14.5%. In 2008, DNA
      fragmentation from the more urbanized watersheds was significantly greater than
      from reference sites (P = 0.026) and in 2009, higher percentages of haploid
      testicular cells were noted from the less urbanized watersheds (P = 0.032)
      indicating better reproductive condition at sites with less urbanization. For
      both years, total and progressive live sperm motilities by computer-assisted
      sperm motion analysis ranged from 19.1% to 76.5%, being significantly higher at
      the less urbanized sites (P < 0.05). This flow cytometric method takes advantage
      of the propensity of fragmented DNA to be denatured under standard conditions, or
      1 minute at 37  degrees C with 10% buffered formalin-fixed cells. The study of
      fixed sperm makes possible the restrospective investigation of germplasm
      fragmentation, spermatogenic ploidy patterns, and chromatin compaction levels
      from samples translocated over distance and time. The protocol provides an
      approach that can be modified for other species across taxa. 

PMID- 25559843
TI  - The role of protein-protein interactions in the intracellular traffic of the
      potassium channels TASK-1 and TASK-3.
AB  - The intracellular transport of membrane proteins is controlled by trafficking
      signals: Short peptide motifs that mediate the contact with COPI, COPII or
      various clathrin-associated coat proteins. In addition, many membrane proteins
      interact with accessory proteins that are involved in the sorting of these
      proteins to different intracellular compartments. In the K2P channels, TASK-1 and
      TASK-3, the influence of protein-protein interactions on sorting decisions has
      been studied in some detail. Both TASK paralogues interact with the adaptor
      protein 14-3-3; TASK-1 interacts, in addition, with the adaptor protein p11
      (S100A10) and the endosomal SNARE protein syntaxin-8. The role of these
      interacting proteins in controlling the intracellular traffic of the channels and
      the underlying molecular mechanisms are summarised in this review. In the case of
      14-3-3, the interacting protein masks a retention signal in the C-terminus of the
      channel; in the case of p11, the interacting protein carries a retention signal
      that localises the channel to the endoplasmic reticulum; and in the case of
      syntaxin-8, the interacting protein carries an endocytosis signal that
      complements an endocytosis signal of the channel. These examples illustrate some
      of the mechanisms by which interacting proteins may determine the itinerary of a
      membrane protein within a cell and suggest that the intracellular traffic of
      membrane proteins may be adapted to the specific functions of that protein by
      multiple protein-protein interactions.

PMID- 25559845
TI  - TRPV4 participates in the establishment of trailing adhesions and directional
      persistence of migrating cells.
AB  - Calcium signaling participates in different cellular processes leading to cell
      migration. TRPV4, a non-selective cation channel that responds to mechano-osmotic
      stimulation and heat, is also involved in cell migration. However, the
      mechanistic involvement of TRPV4 in cell migration is currently unknown. We now
      report that expression of the mutant channel TRPV4-(121)AAWAA (lacking the
      phosphoinositide-binding site (121)KRWRK(125) and the response to physiological
      stimuli) altered HEK293 cell migration. Altered migration patterns included
      periods of fast and persistent motion followed by periods of stalling and
      turning, and the extension of multiple long cellular protrusions. TRPV4-WT
      overexpressing cells showed almost complete loss of directionality with frequent
      turns, no progression, and absence of long protrusions. Traction microscopy
      revealed higher tractions forces in the tail of TRPV4-(121)AAWAA than in TRPV4-WT
      expressing cells. These results are consistent with a defective and augmented
      tail retraction in TRPV4-(121)AAWAA- and TRPV4-WT-expressing cells, respectively.
      The activity of calpain, a protease implicated in focal adhesion (FA)
      disassembly, was decreased in TRPV4-(121)AAWAA compared with TRPV4-WT-expressing
      cells. Consistently, larger focal adhesions were seen in TRPV4-(121)AAWAA
      compared with TRPV4-WT-expressing HEK293 cells, a result that was also reproduced
      in T47D and U87 cells. Similarly, overexpression of the pore-dead mutant TRPV4
      M680D resumed the TRPV4-(121)AAWAA phenotype presenting larger FA. The migratory
      phenotype obtained in HEK293 cells overexpressing TRPV4-(121)AAWAA was mimicked
      by knocking-down TRPC1, a cationic channel that participates in cell migration.
      Together, our results point to the participation of TRPV4 in the dynamics of
      trailing adhesions, a function that may require the interplay of TRPV4 with other
      cation channels or proteins present at the FA sites.

PMID- 25559844
TI  - Dietary potassium and the renal control of salt balance and blood pressure.
AB  - Dietary potassium (K(+)) intake has antihypertensive effects, prevents strokes,
      and improves cardiovascular outcomes. The underlying mechanism for these
      beneficial effects of high K(+) diets may include vasodilation, enhanced urine
      flow, reduced renal renin release, and negative sodium (Na(+)) balance. Indeed,
      several studies demonstrate that dietary K(+) intake induces renal Na(+) loss
      despite elevated plasma aldosterone. This review briefly highlights the
      epidemiological and experimental evidences for the effects of dietary K(+) on
      arterial blood pressure. It discusses the pivotal role of the renal distal tubule
      for the regulation of urinary K(+) and Na(+) excretion and blood pressure and
      highlights that it depends on the coordinated interaction of different nephron
      portions, epithelial cell types, and various ion channels, transporters, and
      ATPases. Moreover, we discuss the relevance of aldosterone and aldosterone
      independent factors in mediating the effects of an altered K(+) intake on renal
      K(+) and Na(+) handling. Particular focus is given to findings suggesting that an
      aldosterone-independent downregulation of the thiazide-sensitive NaCl
      cotransporter significantly contributes to the natriuretic and antihypertensive
      effect of a K(+)-rich diet. Last but not least, we refer to the complex signaling
      pathways enabling the kidney to adapt its function to the homeostatic needs in
      response to an altered K(+) intake. Future work will have to further address the
      underlying cellular and molecular mechanism and to elucidate, among others, how
      an altered dietary K(+) intake is sensed and how this signal is transmitted to
      the different epithelial cells lining the distal tubule. 

PMID- 25559846
TI  - Pseudoislet formation enhances gene expression, insulin secretion and
      cytoprotective mechanisms of clonal human insulin-secreting 1.1B4 cells.
AB  - We have studied the effects of cell communication on human beta cell function and
      resistance to cytotoxicity using the novel human insulin-secreting cell line
      1.1B4 configured as monolayers and pseudoislets. Incubation with the incretin gut
      hormones GLP-1 and GIP caused dose-dependent stimulation of insulin secretion
      from 1.1B4 cell monolayers and pseudoislets. The secretory responses were 1.5-2.7
      fold greater than monolayers. Cell viability (MTT), DNA damage (comet assay) and
      apoptosis (acridine orange/ethidium bromide staining) were investigated following
      2-h exposure of 1.1B4 monolayers and pseudoislets to ninhydrin, H2O2,
      streptozotocin, glucose, palmitate or cocktails of proinflammatory cytokines. All
      agents tested decreased viability and increased DNA damage and apoptosis in both
      1.1B4 monolayers and pseudoislets. However, pseudoislets exhibited significantly
      greater resistance to cytotoxicity (1.5-2.7-fold increases in LD50) and lower
      levels of DNA damage (1.3-3.4-fold differences in percentage tail DNA and olive
      tail moment) and apoptosis (1.3-1.5-fold difference) compared to monolayers.
      Measurement of gene expression by reverse-transcription, real-time PCR showed
      that genes involved with insulin secretion (INS, PDX1, PCSK1, PCSK2, GLP1R and
      GIPR), cell-cell communication (GJD2, GJA1 and CDH1) and antioxidant defence
      (SOD1, SOD2, GPX1 and CAT) were significantly upregulated in pseudoislets
      compared to monolayers, whilst the expression of proapoptotic genes (NOS2, MAPK8,
      MAPK10 and NFKB1) showed no significant differences. In summary, these data
      indicate cell-communication associated with three-dimensional islet architecture
      is important both for effective insulin secretion and for protection of human
      beta cells against cytotoxicity.

PMID- 25559847
TI  - The taste of table salt.
AB  - Solutions of table salt (NaCl) elicit several tastes, including of course
      saltiness but also sweet, sour, and bitter. This brief review touches on some of
      the mileposts concerning what is known about taste transduction for the Na(+)
      ion, the main contributor to saltiness. Electrophysiological recordings,
      initially from single gustatory nerve fibers, and later, integrated impulse
      activity from gustatory nerves led researchers to predict that Na(+) ions
      interacted with a surface molecule. Subsequent studies have resolved that this
      molecule is likely to be an epithelial sodium channel, ENaC. Other Na(+)
      transduction mechanisms are also present in taste buds but have not yet been
      identified. The specific type(s) of taste cells responsible for salt taste also
      remains unknown. 

PMID- 25559849
TI  - Numerical simulation and experimental validation of SiC nanoparticle distribution
      in magnesium melts during ultrasonic cavitation based processing of magnesium
      matrix nanocomposites.
AB  - A two-dimensional coupled model of the temperature field, flow field and pressure
      field of SiC nanoparticles reinforced AZ91D magnesium composite slurries
      fabricated by high-intensity ultrasonic stirring method is established. The
      multiphase flow mixture model is used to simulate the temperature field, flow
      field and pressure field of the semi-solid slurries. The effects of ultrasonic
      stirring parameters on the distribution of SiC nanoparticles in AZ91D magnesium
      alloy melt are simulated by using finite difference method. The simulation
      results show that the distribution uniformity of SiC nanoparticles in Mg melts is
      influenced by ultrasonic power and frequency as well as the ultrasonic processing
      time and depth of ultrasonic probe dipped into the melts, but the ultrasonic
      power and frequency have greater influence on particle distribution. In the
      present work, the magnesium matrix composite with uniform dispersion of SiC
      nanoparticles can be obtained when the ultrasonic power, the ultrasonic
      frequency, the depth of ultrasonic probe dipped into the melts and ultrasonic
      processing time are 2 kW, 20 kHz, 20-30 mm and 120 s, respectively. It has been
      proven that the similar uniform dispersion could be achieved under the optimal
      ultrasonic processing conditions although SiC particle sizes in the agglomerated
      SiC-nanoparticles varied between 30 nm and 300 nm in diameter. Moreover, the
      microstructure and mechanical properties of the SiC nanoparticles reinforced
      AZ91D magnesium alloy based composites obtained experimentally are improved
      significantly by using the optimized ultrasonic processing parameters based on
      numerical simulation.

PMID- 25559848
TI  - Compliance with once-daily versus twice or thrice-daily administration of
      antibiotic regimens: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To investigate whether compliance of patients to antibiotic treatment
      is better when antibiotics are administered once than multiple times daily.
      METHODS: We performed a systematic search in PubMed and Scopus databases. Only
      randomized controlled trials were considered eligible for inclusion. Compliance
      to antibiotic treatment was the outcome of the meta-analysis. RESULTS: Twenty-six
      studies including 8246 patients with upper respiratory tract infections in the
      vast majority met the inclusion criteria. In total, higher compliance was found
      among patients treated with once-daily treatment than those receiving treatment
      twice, thrice or four times daily [5011 patients, RR=1.22 (95% CI, 1.11, 1.34].
      Adults receiving an antibiotic once-daily were more compliant than those
      receiving the same antibiotic multiple times daily [380 patients, RR=1.09 (95%
      CI, 1.02, 1.16)]. Likewise, children that received an antibiotic twice-daily were
      more compliant than those receiving the same antibiotic thrice-daily [2118
      patients, RR=1.10 (95% CI, 1.02, 1.19)]. Higher compliance was also found among
      patients receiving an antibiotic once compared to those receiving an antibiotic
      of different class thrice or four times daily [395 patients, RR=1.20 (95% CI,
      1.12, 1.28)]. The finding of better compliance with lower frequency daily was
      consistent regardless of the study design, and treatment duration. CONCLUSION:
      This meta-analysis showed that compliance to antibiotic treatment might be
      associated with higher when an antibiotic is administered once than multiple
      times daily for the treatment of specific infections and for specific classes of
      antibiotics.

PMID- 25559850
TI  - Benzenediol lactones: a class of fungal metabolites with diverse structural
      features and biological activities.
AB  - Benzenediol lactones are a structurally variable family of fungal polyketide
      metabolites possessing a macrolide core structure fused into a resorcinol
      aromatic ring. These compounds are widespread in fungi mainly in the genera such
      as Aigialus, Cochliobolus, Curvularia, Fusarium, Humicola, Lasiodiplodia,
      Penicillium and Pochonia etc. Most of these fungal metabolites were reported to
      possess several interesting biological activities, such as cytotoxicities,
      nematicidal properties, inhibition of various kinases, receptor agonists, anti
      inflammatory activities, heat shock response and immune system modulatory
      activities etc. This review summarizes the research on the isolation, structure
      elucidation, and biological activities of the benzenediol lactones, along with
      some available structure-activity relationships, biosynthetic studies, first
      syntheses, and syntheses that lead to the revision of structure or
      stereochemistry, published up to the year of 2014. More than 190 benzenediol
      lactones are described, and over 300 references cited. 

PMID- 25559851
TI  - Obstructive sleep apnea in the perioperative setting: complications and
      management strategies.
AB  - Obstructive sleep apnea (OSA) is frequently encountered in an undiagnosed,
      untreated state in perioperative patients. It increases the risk of respiratory,
      cardiac, and infectious complications following surgical procedures. Patients
      with OSA may require additional monitoring, unplanned escalations in care, and
      prolonged hospitalization. It is important to identify patients at risk for OSA
      during the preoperative assessment so that appropriate anesthesia, postsurgical
      monitoring, and pain control can be planned. Herein, we discuss data regarding
      perioperative outcomes in patients with OSA, methods to quickly identify patients
      at high risk for OSA, and implementation of clinical safeguards to minimize OSA
      associated complications. An algorithm is provided to guide the perioperative
      management of patients with OSA.

PMID- 25559852
TI  - Betanin reduces the accumulation and cross-links of collagen in high-fructose-fed
      rat heart through inhibiting non-enzymatic glycation.
AB  - We attempted to determine whether betanin (from natural pigments) that has
      antioxidant properties would be protective against fructose-induced diabetic
      cardiac fibrosis in Sprague-Dawley rats. Fructose water solution (30%) was
      accessed freely, and betanin (25 and 100 mg/kg/d) was administered by intra
      gastric gavage continuously for 60 d. Rats were sacrificed after overnight fast.
      The rat blood and left ventricle were collected. In vitro antiglycation assay in
      bovine serum albumin/fructose system was also performed. In rats treated only
      with fructose, levels of plasma markers: glucose, insulin, HOMA and glycated
      hemoglobin rised, left ventricle collagen accumulated and cross-linked,
      profibrotic factor-transforming growth factor (TGF)-beta1 and connective tissue
      growth factor (CTGF) protein expression increased, and soluble collagen
      decreased, compared with those in normal rats, showing fructose induces diabetic
      cardiac fibrosis. Treatment with betanin antagonized the changes of these
      parameters, demonstrating the antifibrotic role of betanin in the selected
      diabetic models. In further mechanistic study, betanin decreased protein
      glycation indicated by the decreased levels of protein glycation reactive
      intermediate (methylglyoxal), advanced glycation end product (N(epsilon)
      (carboxymethyl) lysine) and receptors for advanced glycation end products (AGEs),
      antagonized oxidative stress and nuclear factor-kappaB activation elicited by
      fructose feeding, suggesting inhibition of glycation, oxidative stress and
      nuclear factor-kappaB activation may be involved in the antifibrotic mechanisms.
      Betanin also showed anitglycative effect in BSA/fructose system, which supported
      that anitglycation was involved in betanin's protective roles in vivo. Taken
      together, the potential for using betanin as an auxillary therapy for diabetic
      cardiomyopathy deserves to be explored further.

PMID- 25559853
TI  - STAT3-dependent VEGF production from keratinocytes abrogates dendritic cell
      activation and migration by arsenic: a plausible regional mechanism of
      immunosuppression in arsenical cancers.
AB  - Arsenic remains an important environmental hazard that causes several human
      cancers. Arsenic-induced Bowen's disease (As-BD), a skin carcinoma in situ, is
      the most common arsenical cancer. While great strides have been made in our
      understanding of arsenic carcinogenesis, how host immunity contributes to this
      process remains unknown. Patients with As-BD have an impaired contact
      hypersensitivity response. Although impaired T cell activation has been well
      documented in arsenical cancers, how dendritic cell (DC), the key cell regulating
      innate immunity, regulates the immune response in arsenical cancers remains
      unclear. Using myeloid derived DC (MDDC) from patients with As-BD and normal
      controls as well as bone marrow derived DC (BMDC) from mice fed with or without
      arsenic, we measured the migration of DC. As-BD patients showed an impaired CCL21
      mediated MDDC migration in vitro. Arsenic-fed mice had defective DC migration
      toward popliteal lymph nodes when injected with allogenic BMDCs via foot pad.
      Using skin from As-BD and normal controls, we found an increased expression of
      STAT3, a transcriptional factor contributing to impaired DC activation. Arsenic
      induced STAT3 activation and the production of VEGF in keratinocytes. The
      increase in VEGF was blocked by inhibiting STAT3 with RNA interference or
      pharmaceutically with JSI-124. While VEGF by itself minimally induced the
      expression of CD86 and MHC-II in MDDC, arsenic induced-MDDC activation was
      abolished by VEGF pretreatment. We concluded that the STAT3-VEGF axis in
      keratinocytes inhibits DC migration in the microenvironment of As-BD, indicating
      that cellular interactions play an important role in regulating the disease
      course of arsenical cancers. 

PMID- 25559854
TI  - Systemic uptake, albumin and hemoglobin binding of [(14)C]2,3-butanedione
      administered by intratracheal instillation in male Harlan Sprague Dawley rats and
      oropharyngeal aspiration in male B6C3F1/N mice.
AB  - 2,3-Butanedione (BD) is a reactive diketone in artificial butter flavors that is
      thought to cause bronchiolitis obliterans in workers in microwave popcorn
      manufacturing. Bronchiolitis obliterans is generally not diagnosed until
      irreversible damage has occurred; therefore a biomarker of early exposure is
      needed. The potential systemic uptake of BD from inhalation exposure has not been
      evaluated. The objective here was to evaluate the systemic exposure of BD and
      binding to hemoglobin and albumin. [(14)C]BD was administered to male Harlan
      Sprague Dawley rats (100 mg/kg, intratracheal instillation) and B6C3F1/N mice
      (157 mg/kg, oropharyngeal aspiration). Blood and plasma was collected 24 h after
      administration and analyzed for (14)C content. At 24h, 0.88+/-0.07% of the
      administered dose was in rat blood, 0.66+/-0.06% in rat plasma, 0.38+/-0.13% in
      mouse blood and 0.17+/-0.05% in mouse plasma. Albumin binding in rats was 269+/
      24.2 ng equiv./mg, which accounts for 38% of the radioactivity in plasma. In
      mice, binding was 85.0+/-22.3 ng equiv./mg albumin, which accounts for 51% of the
      radioactivity in plasma. The binding to hemoglobin in rats was 38.2+/-17.6 ng
      equiv./mg, and to globin was 29.1+/-3.96 ng equiv./mg. In mice, the binding to
      hemoglobin was 16.2+/-9.0 ng equiv./mg. The site(s) of adduction on hemoglobin
      and albumin was investigated by mass spectrometry. In rat globin, arginine
      adducts were detected at R-30 and R-104 of the beta chain in vitro and in vivo.
      In rat albumin, adducts were detected in vitro on R-219/221, R-360, and R-368,
      and in vivo on a variety of arginine residues. This study demonstrated that BD
      enters the systemic circulation and reacts with arginine on hemoglobin and
      albumin. These results indicate that hemoglobin and albumin adducts may be useful
      as biomarkers of BD exposure in humans.

PMID- 25559855
TI  - Isolation and identification of a repressor TetR for 3,17beta-HSD expressional
      regulation in Comamonas testosteroni.
AB  - Comamonas testosteroni (C. testosteroni) is able to catabolize a variety of
      steroids and polycyclic aromatic hydrocarbons. 3,17beta-Hydroxysteroid
      dehydrogenase (3,17beta-HSD) from C. testosteroni is a key enzyme in steroid
      degradation. Understanding the mechanism of 3,17beta-HSD gene (betahsd) induction
      may help us to elucidate its complete molecular regulation. Sequencing the C.
      testosteroni ATCC11996 genome lead us to identify the tetR (522 bp) downstream of
      betahsd. Two repeat sequences (RS; 13 bp), that are separated to each other by
      1661 bp, were found upstream of betahsd. A bioinformatic analysis revealed that
      TetR family proteins act as transcriptional repressors which are sensitive to
      environmental signals. Since, C. testosteroni responds to environmental steroid
      induction and upregulates steroid catabolic genes, we hypothesized that TetR
      might act in C. testosteroni as repressor for betahsd expression. The tetR was
      cloned into different plasmids, including an EGFP reporter system, for functional
      characterization and/or overexpression. The data indicate that, indeed, TetR acts
      as a repressor for 3,17beta-HSD expression. Testosterone in turn, which is known
      to induce betahsd expression, could not resolve TetR repression. To further
      substantiate TetR as repressor for betahsd expression, a tetR gene knock-out
      mutant of C. testosteroni was generated. TetR gene knock-out mutants showed the
      same basal low level of betahsd expression as the C. testosteroni wild type
      cells. Interestingly, testosterone induction leads to a strong increase in
      betahsd expression, especially in the tetR gene knock-out mutants. The result
      with the knock-out mutant, in principle, supports our hypothesis that TetR is a
      repressor for betahsd expression, but the exact role of testosterone in this
      context remains unknown. Finally, it turned out that TetR is obviously also
      involved in the regulation of the hsdA gene.

PMID- 25559857
TI  - Resveratrol inhibits high glucose induced collagen upregulation in cardiac
      fibroblasts through regulating TGF-beta1-Smad3 signaling pathway.
AB  - Cardiac fibrosis is a common pathological process presented in a variety of
      diseases, including hypertension and diabetes. Cardiac fibroblasts (CFs) have
      been identified as the most important participants in the development of cardiac
      fibrosis. Exposure of cultured CFs to high glucose (HG) or angiotensin II (Ang
      II) resulted in increased collagen synthesis. Resveratrol (Res) is a natural
      polyphenol exhibiting anti-fibrosis effects in a number of different organs
      fibrosis process, whether Res can prevent HG and Ang II induced fibrosis response
      in CFs remains unclear. The aim of this work was to evaluate the effects of Res
      in HG and Ang II induced fibrosis response in CFs. We cultured rat CFs in either
      normal glucose (5.6 mM) or HG (25 mM) media in the presence of Res or not and the
      changes in collagens synthesis and TGF-beta1 production were assessed by Real
      time PCR, Western blotting, and enzyme linked immunosorbent assay (ELISA).
      Furthermore, normal and diabetic mice (induced by single dose of streptozotocin
      (100 mg/kg) via tail vein) receiving Res (10 mg/kg) were used to explore the
      effects of Res on cardiac fibrosis in vivo. Masson staining and
      immunohistochemistry were performed to visualize cardiac collagen deposition.
      Results indicate that CFs exposed to HG condition shows enhanced proliferation
      rate. Furthermore, in the presence of HG or Ang II, CFs exhibited increased
      collagens synthesis and TGF-beta1 production. And these effects were abolished by
      Res intervention. In vivo results show that diabetic mice exhibit increased
      collagen deposition in the cardiac compared with the normal mice. And this change
      was prevented by the treatment of Res. These results suggest that Res possesses a
      potential antifibrogenic effect in hypertension and diabetes-related cardiac
      fibrosis. Moreover, the action mechanism is probably associated with its ability
      to reduce TGF-beta1 content in CFs.

PMID- 25559858
TI  - Nitric oxide-releasing indomethacin enhances susceptibility to Trypanosoma cruzi
      infection acting in the cell invasion and oxidative stress associated with
      anemia.
AB  - Trypanosoma cruzi is the causative agent of Chagas disease. Approximately 8
      million people are thought to be affected with this disease worldwide. T. cruzi
      infection causes an intense inflammatory response, which is critical for the
      control of parasite proliferation and disease development. Nitric oxide-donating
      nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are an emergent class of
      pharmaceutical derivatives with promising utility as chemopreventive agents. In
      this study, we investigated the effect of NO-indomethacin on parasite burden,
      cell invasion, and oxidative stress in erythrocytes during the acute phase of
      infection. NO-indomethacin was dissolved in dimethyl formamide followed by i.p.
      administration of 50 ppm into mice 30 min after infection with 5*10(3) blood
      trypomastigote forms (Y strain). The drug was administered every day until the
      animals died. Control animals received 100 MUL of drug vehicle via the same
      route. Within the NO-indomethacin-treatment group, parasitemia and mortality
      (100%) were higher and oxidative stress in erythrocytes, anemia, and entry of
      parasites into macrophages were significantly greater than that seen in controls.
      Increase in the entry and survival of intracellular T. cruzi was associated with
      inhibition of nitric oxide production by macrophages treated with NO-indomethacin
      (2.5 MUM). The results of this study provide strong evidence that NO-NSAIDs
      potently inhibit nitric oxide production, suggesting that NO-NSAID-based
      therapies against infections would be difficult to design and would require
      caution.

PMID- 25559859
TI  - Blockade of lipid accumulation by silibinin in adipocytes and zebrafish.
AB  - Silibinin is a compound present mainly in milk thistle. In this study, we
      investigated the mechanism by which silibinin suppresses adipogenesis of 3T3-L1
      cells, and evaluated the anti-adipogenic effect of silibinin in zebrafish.
      Silibinin reduced lipid accumulation by downregulating adipogenic factors, such
      as, peroxisome proliferator-activated receptor gamma (PPARgamma), CCAAT-enhancer
      binding protein alpha (C/EBPalpha), and fatty acid-binding protein 4 (FABP4). The
      reduction of these adipogenic protein levels was associated with the regulation
      of early adipogenic factors, such as, C/EBPbeta and Kruppel-like factor 2 (KLF2),
      and was reflected in downregulation of lipid synthetic enzymes. Silibinin
      arrested cells in the G0/G1 phase of the cell cycle, accompanied by
      downregulation of cyclins and upregulation of p27, a cell cycle inhibitor. These
      results correlated with the finding of deactivation of extracellular signal
      regulated kinase (ERK) and AKT, a serine/threonine-specific kinase. In addition,
      silibinin activated AMP-activated protein kinase alpha (AMPKalpha) to inhibit
      fatty acid synthesis. As observed in 3T3-L1 cells, silibinin inhibited lipid
      accumulation in zebrafish with the reduction of adipogenic factors and
      triglyceride levels. Our data revealed that silibinin inhibited lipid
      accumulation in 3T3-L1 cells and zebrafish, and this inhibitory effect was
      associated with abrogation of early adipogenesis via regulation of cell cycle and
      AMPKalpha signaling. 

PMID- 25559860
TI  - Comparison of improved prognosis between hepatitis B- and hepatitis C-related
      hepatocellular carcinoma.
AB  - AIM: Treatment strategies for hepatocellular carcinoma (HCC) have been advanced.
      The aim of this study was to compare the change of the prognosis between
      hepatitis B-related HCC (B-HCC) and hepatitis C-related HCC (C-HCC) in the last
      two decades. METHODS: We enrolled 166 B-HCC patients who underwent percutaneous
      ablation between 1990 and 2009. Patients were divided into three groups according
      to the treatment time period: 1990-1995 (cohort 1, n = 19), 1996-2002 (cohort 2,
      n = 49) and 2003-2009 (cohort 3, n = 98). We enrolled 1219 C-HCC patients who
      underwent percutaneous ablation during the same period (n = 190, 413 and 616,
      respectively.). Interferon and nucleoside/nucleotide analog use was investigated.
      Prognosis was evaluated for each cohort using the Kaplan-Meier method and a
      multivariate Cox proportional hazard regression model. RESULTS: Two (11%), 24
      (49%) and 80 (82%) B-HCC patients received nucleoside/nucleotide analogs during
      the follow-up period in cohorts 1-3, respectively. Among them 1, 18 and 62
      patients achieved viral remission, respectively. Thirty-four (18%), 35 (8%) and
      84 (14%) C-HCC patients received interferon therapy, respectively. The 5-year B
      HCC (P < 0.001) survival rates were 52.6%, 61.1% and 81.6% for cohorts 1-3,
      respectively. However, the survival rates were 55.6%, 58.8% and 61.1% for C-HCC
      (P = 0.12), respectively. The B-HCC prognosis improved dramatically (P < 0.001)
      over time, whereas the prognosis of C-HCC improved moderately (P = 0.01).
      CONCLUSION: The prognosis of B-HCC has improved dramatically over time, whereas
      that of C-HCC has improved moderately.

PMID- 25559856
TI  - Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls.
AB  - Extensive research has shown that increased production of reactive oxygen species
      (ROS) results in tissue injury under a variety of pathological conditions and
      chronic degenerative diseases. While ROS are highly reactive and can incite
      significant injury, polyunsaturated lipids in membranes and lipoproteins are
      their main targets. ROS-triggered lipid-peroxidation reactions generate a range
      of reactive carbonyl species (RCS), and these RCS spread and amplify ROS-related
      injury. Several RCS generated in oxidizing lipids, such as 4-hydroxy trans-2
      nonenal (HNE), 4-oxo-2-(E)-nonenal (ONE), acrolein, malondialdehyde (MDA) and
      phospholipid aldehydes have been shown to be produced under conditions of
      oxidative stress and contribute to tissue injury and dysfunction by depleting
      glutathione and other reductants leading to the modification of proteins, lipids,
      and DNA. To prevent tissue injury, these RCS are metabolized by several
      oxidoreductases, including members of the aldo-keto reductase (AKR) superfamily,
      aldehyde dehydrogenases (ALDHs), and alcohol dehydrogenases (ADHs). Metabolism
      via these enzymes results in RCS inactivation and detoxification, although under
      some conditions, it can also lead to the generation of signaling molecules that
      trigger adaptive responses. Metabolic transformation and detoxification of RCS by
      oxidoreductases prevent indiscriminate ROS toxicity, while at the same time,
      preserving ROS signaling. A better understanding of RCS metabolism by
      oxidoreductases could lead to the development of novel therapeutic interventions
      to decrease oxidative injury in several disease states and to enhance resistance
      to ROS-induced toxicity. 

PMID- 25559861
TI  - A novel method for comparison of biocidal properties of nanomaterials to
      bacteria, yeasts and algae.
AB  - Toxicity testing of nanomaterials (NMs) is experimentally challenging because NMs
      may interfere with test environment and assay components. In this work we propose
      a simple and reliable method--a 'spot test' to compare biocidal potency of NMs to
      unicellular microorganisms such as bacteria, yeasts and algae. The assay is
      straightforward: cells are incubated in deionized water suspensions of NMs for up
      to 24h and then pipetted as a 'spot' on agarized medium. Altogether seven
      bacterial strains, yeast and a microalga were tested. CuO, TiO2 and two different
      Ag NPs, multi-wall C-nanotubes (MWCNTs), AgNO3, CuSO4, 3,5-dichlorophenol,
      triclosan and H2O2 were analyzed. The biocidal potency of tested substances
      ranged from 0.1mg/L to >1000 mg/L; whereas, the least potent NMs toward all test
      species were TiO2 NPs and MWCNTs and most potent Ag and CuO NPs. Based on the
      similar toxicity pattern of the tested chemicals on the nine unicellular
      organisms in deionized water we conclude that toxicity mechanism of biocidal
      chemicals seems to be similar, whatever the organism (bacteria, yeast, alga).
      Therefore, when the organisms are not 'protected' by their environment that
      usually includes various organic and inorganic supplements their tolerance to
      toxicants is chemical- rather than organism-dependent.

PMID- 25559862
TI  - An active dealkalization of red mud with roasting and water leaching.
AB  - The research has focused on the dealkalization of red mud after active roasting
      and water leaching, which is obtained from bauxite during alumina production. The
      main factors such as roasting temperature, roasting time, water leaching stage,
      leaching temperature, leaching reaction time and liquid to solid ratio were
      investigated. The mechanism of dealkalization was in-depth studied by using ICP
      AES, XRD, TG-DSC, SEM-EDS and leaching kinetic. The results show that the
      dealkalization rate reached 82% under the condition of roasting temperature of
      700  degrees C, roasting time of 30 min, four stage water leaching, liquid to
      solid ratio of 7 mL/g, leaching temperature of 90  degrees C and reaction time of
      60 min. The diffraction peak of Na6CaAl6Si6(CO3)O24 . 2H2O in red mud was
      decreased during the active roasting process, whereas the mineral phases of NaOH
      . H2O and Na2Ca(CO3)2 were appeared. The content of alkali obviously decreased
      and the grade of other elements increased during the process of active roasting
      and water leaching, which was in favor of next application process of red mud.
      The water leaching was controlled by internal diffusion of SCM and the apparent
      activation energy was 22.63 kJ/mol.

PMID- 25559863
TI  - Evaluation of ethyl tert-butyl ether biodegradation in a contaminated aquifer by
      compound-specific isotope analysis and in situ microcosms.
AB  - Ethyl tert-butyl ether (ETBE) is an upcoming groundwater pollutant in Europe
      whose environmental fate has been less investigated, thus far. In the present
      study, we investigated the in situ biodegradation of ETBE in a fuel-contaminated
      aquifer using compound-specific stable isotope analysis (CSIA), and in situ
      microcosms in combination with total lipid fatty acid (TLFA)-stable isotope
      probing (SIP). In a first field investigation, CSIA revealed insignificant carbon
      isotope fractionation, but low hydrogen isotope fractionation of up to +140/00
      along the prevailing anoxic ETBE plume suggesting biodegradation of ETBE. Ten
      months later, oxygen injection was conducted to enhance the biodegradation of
      petroleum hydrocarbons (PH) at the field site. Within the framework of this
      remediation measure, in situ microcosms loaded with [(13)C6]-ETBE (BACTRAP((r))s)
      were exposed for 119 days in selected groundwater wells to assess the
      biodegradation of ETBE by TLFA-SIP under the following conditions: (i) ETBE as
      main contaminant; (ii) ETBE as main contaminant subjected to oxygen injection;
      (iii) ETBE plus other PH; (iv) ETBE plus other PH subjected to oxygen injection.
      Under all conditions investigated, significant (13)C-incorporation into microbial
      total lipid fatty acids extracted from the in situ microcosms was found,
      providing clear evidence of ETBE biodegradation. 

PMID- 25559864
TI  - Novel self-assembled bimetallic structure of Bi/Fe(0): the oxidative and
      reductive degradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).
AB  - A novel self-assembled bimetallic zero-valent bismuth/iron (Bi/Fe(0)) composite
      was synthesized, characterized, and used successfully to remove hexahydro-1,3,5
      trinitro-1,3,5-triazine (RDX) from wastewater. To assess the oxidative and
      reductive reactivities of Bi/Fe(0) nanoparticles (NPs), RDX degradation
      experiments were conducted in either ambient or anaerobic conditions,
      respectively. The best RDX degradation was achieved using 4%-Bi/Fe(0) (atomic
      ratio) NPs. In ambient conditions, concentrations of Fe(2+) ions and H2O2 were
      lower in the Bi/Fe(0) solution than in the Fe(0) solution; this difference
      indicates that most Fe(2+) ions and H2O2 reacted to produce hydroxyl radicals
      (*OH) and superoxide radical anions (O2(*-)), thereby resulting in the remarkable
      degradation of RDX. In anaerobic conditions, the presence of Bi increased the
      electron generation rate from the surfaces of the Bi/Fe(0) NPs. This increase was
      responsible for the excellent reductive degradation of RDX. Based on Density
      Functional Theory (DFT) calculations, the adsorption of water was endothermic on
      Fe(0) NPs and exothermic on Bi/Fe(0) NPs. Therefore, only the dissociation
      reactions of H2O in the Bi/Fe(0) system were spontaneous, and these reactions
      resulted in the prominent reactivity of the Bi/Fe(0) NPs.

PMID- 25559865
TI  - Systematic approach to Escherichia coli cell population control using a genetic
      lysis circuit.
AB  - BACKGROUND: Cell population control allows for the maintenance of a specific cell
      population density. In this study, we use lysis gene BBa_K117000 from the
      Registry of Standard Biological Parts, formed by MIT, to lyse Escherichia coli
      (E. coli). The lysis gene is regulated by a synthetic genetic lysis circuit,
      using an inducer-regulated promoter-RBS component. To make the design more
      easily, it is necessary to provide a systematic approach for a genetic lysis
      circuit to achieve control of cell population density. RESULTS: Firstly, the
      lytic ability of the constructed genetic lysis circuit is described by the
      relationship between the promoter-RBS components and inducer concentration in a
      steady state model. Then, three types of promoter-RBS libraries are established.
      Finally, according to design specifications, a systematic design approach is
      proposed to provide synthetic biologists with a prescribed I/O response by
      selecting proper promoter-RBS component set in combination with suitable inducer
      concentrations, within a feasible range. CONCLUSION: This study provides an
      important systematic design method for the development of next-generation
      synthetic gene circuits, from component library construction to genetic circuit
      assembly. In future, when libraries are more complete, more precise cell density
      control can be achieved.

PMID- 25559866
TI  - Cocoa-rich diet attenuates beta cell mass loss and function in young Zucker
      diabetic fatty rats by preventing oxidative stress and beta cell apoptosis.
AB  - We have recently shown that cocoa flavanols may have anti-diabetic potential by
      promoting survival and function of pancreatic beta-cells in vitro. In this work,
      we investigated if a cocoa-rich diet is able to preserve beta-cell mass and
      function in an animal model of type 2 diabetes and the mechanisms involved. Our
      results showed that cocoa feeding during the prediabetic state attenuates
      hyperglycaemia, reduces insulin resistant, and increases beta cell mass and
      function in obese Zucker diabetic rats. At the molecular level, cocoa-rich diet
      prevented beta-cell apoptosis by increasing the levels of Bcl-xL and decreasing
      Bax levels and caspase-3 activity. Cocoa diet enhanced the activity of endogenous
      antioxidant defenses, mainly glutathione peroxidase, preventing thus oxidative
      injury induced by the pre-diabetic condition and leading to apoptosis prevention.
      These findings provide the first in vivo evidence that a cocoa-rich diet may
      delay the loss of functional beta-cell mass and delay the progression of diabetes
      by preventing oxidative stress and beta-cell apoptosis. 

PMID- 25559867
TI  - Orientation in multi-layer chitosan hydrogel: morphology, mechanism, and design
      principle.
AB  - Hydrogels with organized structure have attracted remarkable attentions for bio
      related applications. Among the preparation of hierarchical hydrogel materials,
      fabrication of hydrogel with multi-layers is an important branch. Although the
      generation mechanism of layers had been fully discussed, sub-layer structure was
      not sufficiently studied. In this research, multi-layered chitosan hydrogel with
      oriented structure was constructed, and the formation mechanism of orientation
      was proposed, based on gelation behavior and entanglement of polymer chains in
      the hydrogel-solution system. Employing the layered-oriented characteristic,
      chitosan hydrogel materials with various shapes and structure can be designed and
      fabricated. 

PMID- 25559868
TI  - Resident duty hours: past, present, and future.

PMID- 25559869
TI  - Elastomeric core/shell nanofibrous cardiac patch as a biomimetic support for
      infarcted porcine myocardium.
AB  - Heart failure due to Myocardial Infarction (MI) remains the leading cause of
      death worldwide due to the inability of myocardial tissue to regenerate following
      infarction. Current therapies could only retard the progression of disease, but
      fails to bring functional improvement and cardiac regeneration. The present study
      analyzes the potentials of Poly(glycerol sebacate)/Fibrinogen (PGS/Fib)
      core/shell fibers as a structural support and initial entrapment of cells in an
      in vivo porcine model using echocardiography, histology, and
      immunohistochemistry. The echocardiography results showed the increased ejection
      fraction (EF) in PGS/Fib/VEGF/Cells compared with MI controls. The percentage
      increase in the End Diastolic Volume (EDV) dimension from post MI period to 4
      weeks follow-up was the least in PGS/Fib/VEGF/Cells groups compared with MI and
      cell control group proving that the PGS/Fib/VEGF/Cells group restored the left
      ventricle (LV) function after MI, evident from the improvement in EF and
      prevention of LV enlargement. Further, immunohistochemistry results demonstrated
      that most of the transplanted mesenchymal stem cells (MSCs) within the
      PGS/Fib/VEGF scaffolds expressed cardiac marker proteins troponin and actinin and
      endothelial cell marker protein CD31 indicating differentiation of human bone
      marrow MSCs into cardiac cells and endothelial cells. The developed nanofibrous
      cardiac patch PGS/Fib/VEGF/Cells provides both functional and structural
      integrity to the infarcted myocardium and also serves as a suitable matrix for
      the entrapment of MSCs in clinical applications for cardiac tissue engineering. 

PMID- 25559870
TI  - A randomized comparison of the i-gel with the self-pressurized air-Q intubating
      laryngeal airway in children.
AB  - BACKGROUND: Supraglottic airway devices with noninflatable cuff have advantages
      in omitting the cuff pressure monitoring and reducing potential pharyngolaryngeal
      complications. Typical devices without cuff inflation available in children are
      the i-gel and the self-pressurized air-Q intubating laryngeal airway (air-Q SP).
      To date, there is no comparative study between these devices in pediatric
      patients. AIM: The purpose of this randomized study was to compare the i-gel(TM)
      and the self-pressurized air-Q(TM) intubating laryngeal airway (air-Q SP) in
      children undergoing general anesthesia. METHODS: Eighty children, 1-108 months of
      age, 7-30 kg of weight, and scheduled for elective surgery in which supraglottic
      airway devices would be suitable for airway management, were randomly assigned to
      either the i-gel or the air-Q SP. Oropharyngeal leak pressure and fiberoptic view
      were assessed three times as follows: after insertion and fixation of the device,
      10 min after initial assessment, and after completion of surgery. We also
      assessed insertion parameters and complications. RESULTS: Insertion of the i-gel
      was regarded as significantly easier compared to the air-Q SP (P = 0.04).
      Compared to the air-Q SP group, the i-gel group had significantly higher
      oropharyngeal leak pressures at all measurement points and significantly lower
      frequencies of gastric insufflation at 10 min after initial assessment and
      completion of surgery. The air-Q SP group had better fiberoptic views than the i
      gel group at all measurement points. CONCLUSION: Our results showed that the i
      gel had easier insertion and better sealing function, and the air-Q SP provided
      improved fiberoptic views in children requiring general anesthesia.

PMID- 25559872
TI  - Stability of silver nanowire based electrodes under environmental and electrical
      stresses.
AB  - Flexible transparent electrodes fabricated with random networks of silver
      nanowires (AgNWs) have been widely studied in recent years. This approach appears
      to be a promising alternative to replace ITO (indium tin oxide) in many
      optoelectronic applications. Many successful integrations in functional devices
      have already evidenced the high potential of this technology, but unfortunately
      only very few studies have been dedicated so far to the stability of this
      material. We present here a study dealing with the alteration of the electrical
      properties of AgNW meshes when subjected to different stresses. We demonstrate
      that AgNW electrodes are very stable when stored under ambient atmosphere up to,
      at least, two and a half years. Accelerated ageing processes also reveal that
      concentrated H2S or exposure to light does not cause any significant sheet
      resistance modification. However, the combination of high relative humidity and
      high temperature seems to be more critical. In addition, long lasting contact
      (two years) with PEDOT:PSS can induce deterioration of the electrical properties.
      Similarly, AgNW/PEDOT:PSS hybrid materials exhibit weaker stability under
      electrical stress when compared to pristine AgNW networks.

PMID- 25559871
TI  - Delusions and prediction error: clarifying the roles of behavioural and brain
      responses.
AB  - Griffiths and colleagues provided a clear and thoughtful review of the prediction
      error model of delusion formation [Cognitive Neuropsychiatry, 2014 April 4 (Epub
      ahead of print)]. As well as reviewing the central ideas and concluding that the
      existing evidence base is broadly supportive of the model, they provide a
      detailed critique of some of the experiments that we have performed to study it.
      Though they conclude that the shortcomings that they identify in these
      experiments do not fundamentally challenge the prediction error model, we
      nevertheless respond to these criticisms. We begin by providing a more detailed
      outline of the model itself as there are certain important aspects of it that
      were not covered in their review. We then respond to their specific criticisms of
      the empirical evidence. We defend the neuroimaging contrasts that we used to
      explore this model of psychosis arguing that, while any single contrast entails
      some ambiguity, our assumptions have been justified by our extensive background
      work before and since. 

PMID- 25559873
TI  - The outcomes of adult liver transplants in the United States from 1987 to 2013.
AB  - BACKGROUND & AIMS: In the past three decades, there have been major advances in
      the procedure and candidate selection for liver transplantation. The aim of this
      study was to assess the changes in outcomes of liver transplantations in the
      Unites States. METHODS: This observational study uses the Scientific Registry of
      Transplant Recipients (SRTR) that includes all liver transplants from 1987 to
      2013 (N = 108 707 adults). RESULTS: Four study cycles were introduced: 1987-1993,
      1994-2000, 2001-2006, 2007-2013. The length of inpatient stay for receiving liver
      transplant substantially shortened (42-20 days), and so did the rate of acute
      post-transplant rejections (33-4%). The use of high risk donors and donors with
      chronic diseases increased significantly. Of transplant outcomes, despite
      recently reported unfavourable changes in clinico-demographic profile of liver
      transplant recipients (older age, substantial increases in all major
      comorbidities), the proportion of patients discharged alive increased from 78.2
      to 91.8%. On the other hand, post-discharge 1-, 3- and 5-year mortality varied
      between 6.7 and 8.0%, 15.2 to 17.2% and 22.5 to 24.5%, respectively, and no
      consistent trend was found. Despite this, the rates of graft failure decreased:
      an approximately two-fold decrease in 1 year graft loss, and a 1.6-fold decrease
      in 5 year graft loss were observed. CONCLUSION: Despite all improvements in liver
      transplant technique and patient management, the changes in post-transplant
      outcomes vary. While inpatient mortality, graft losses and post-transplant infect
      ion rates improved substantially, post-discharge mortality remains stable because
      of increasing losses to competing risks in patients with non-liver comorbidities.

PMID- 25559874
TI  - GWAMAR: genome-wide assessment of mutations associated with drug resistance in
      bacteria.
AB  - BACKGROUND: Development of drug resistance in bacteria causes antibiotic
      therapies to be less effective and more costly. Moreover, our understanding of
      the process remains incomplete. One promising approach to improve our
      understanding of how resistance is being acquired is to use whole-genome
      comparative approaches for detection of drug resistance-associated mutations.
      RESULTS: We present GWAMAR, a tool we have developed for detecting of drug
      resistance-associated mutations in bacteria through comparative analysis of whole
      genome sequences. The pipeline of GWAMAR comprises several steps. First, for a
      set of closely related bacterial genomes, it employs eCAMBer to identify
      homologous gene families. Second, based on multiple alignments of the gene
      families, it identifies mutations among the strains of interest. Third, it
      calculates several statistics to identify which mutations are the most associated
      with drug resistance. CONCLUSIONS: Based on our analysis of two large datasets
      retrieved from publicly available data for M. tuberculosis, we identified a set
      of novel putative drug resistance-associated mutations. As a part of this work,
      we present also an application of our tool to detect putative compensatory
      mutations.

PMID- 25559875
TI  - Transversal modulation ion mobility spectrometry (IMS) coupled with mass
      spectrometry (MS): exploring the IMS-IMS-MS possibilities of the instrument.
AB  - A prototype is introduced based on the transversal modulation ion mobility
      spectrometry (TMIMS) technique, which provides a continuous output of mobility
      selected ions, greatly easing the synchronization between different analyzing
      stages. In the new architecture, two stages of filtration are used to drastically
      reduce the background produced by one stage alone. Two-stages TMIMS was coupled
      with two different atmospheric pressure interface mass spectrometers (MS). The
      new system enables IMS-IMS-MS analysis and other modes of operation: IMS
      prefiltration, IMS-IMS, and full transmission mode. It provides a resolving power
      R > 60 in IMS mode, and R > 40 in each stage of IMS-IMS mode. 2-Propanol vapors
      were introduced in one of the stages to enhance the mobility variations, and
      their effect was studied on a set of tetraalkylammonium ions. We found that
      concentrations as low as 1% (in partial pressure) produce mobility variations as
      high as 20%, which suggest that IMS-IMS separation using dried N2 (in one stage)
      and a dopant (in the other stage), could be a very powerful way to enhance the
      separation capacity of the IMS-IMS prefiltration approach. 

PMID- 25559876
TI  - Revision TKA for Flexion Instability Improves Patient Reported Outcomes.
AB  - Instability is a major cause of early revision of total knee arthroplasty (TKA),
      of which flexion instability is a major subset. We analyzed radiologically
      evident corrections, patient reported outcome and complications associated with
      revision TKA for flexion instability in a retrospective cohort of 37 patients
      with minimum one year follow up. Following revision surgery, there was a
      significant increase in mean posterior condylar offset ratio and a significant
      decrease in tibial slope while the level of joint line was not significantly
      altered. Patient reported version of knee society score showed significant
      improvement with surgery and 26 of 37 patient reported perceptible improvement on
      a 7-point Likert scale. LEVEL OF EVIDENCE: Level IV, Case series. See the
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 25559877
TI  - Metacognitive executive function training for young children with ADHD: a proof
      of-concept study.
AB  - Executive functions (EF) are impaired in children with attention
      deficit/hyperactivity disorder (ADHD). It may be especially critical for
      interventions to target EF in early childhood given the developmental progression
      of EF deficits that may contribute to later functional impairments. This proof-of
      concept study examined the initial efficacy of an intervention program on EF and
      ADHD. We also examined child performance on three neurocognitive tasks assessing
      cognitive flexibility, auditory/visual attention, and sustained/selective
      attention. Children with ADHD (ages 3-7) and their parents were randomized to
      receive an intervention targeting metacognitive EF deficits (n = 13) or to a
      waitlist control condition (n = 12). Linear model analysis of covariance compared
      groups on parent EF ratings, blinded clinician ratings of ADHD symptoms and
      improvement, and child performance on neurocognitive measures. Children who
      received the intervention significantly improved on parent ratings of attention
      shifting and emotion regulation in addition to clinician ratings of inattention.
      Moderate effect sizes showed additional intervention effects on parent ratings of
      inhibition, memory, and planning, and clinician ratings of
      hyperactivity/impulsivity and overall improvement. Small effect sizes were
      observed for improvement on child neurocognitive measures. Although replication
      with a larger sample and an active control group is needed, EF training with a
      metacognitive focus is a potentially promising intervention for young children
      with ADHD. 

PMID- 25559878
TI  - Hydrophobic effects within the dynamic pH-response of polybasic tertiary amine
      methacrylate brushes.
AB  - The solvation and swelling behaviour of three dialkylaminoethyl methacrylate
      polymer brushes, of varying hydrophobicity, have been investigated using a
      combination of in situ ellipsometry and a quartz crystal microbalance with
      dissipation (QCM-D). At low pH the tertiary amine groups of the three polymers
      are protonated and all three brushes are significantly solvated and swell by
      adopting an extended conformation. As the pH is increased the weak polybasic
      brushes become increasingly deprotonated and collapse via solvent expulsion. By
      employing high temporal resolution measurements we have found that monomer
      hydrophobicity has a direct influence on the dynamics of this pH-response. The
      most hydrophobic poly(2-diisopropylamino)ethyl methacrylate (poly(DPA)) brush
      exhibits the fastest maximum swelling rate. This maximum swelling rate is reduced
      with decreasing monomer hydrophobicity for the 2-diethylamino, and even further
      for the 2-dimethylamino analogues. For all three brushes, the corresponding
      collapse transition is slower and compounded by an induction time that decreases
      with monomer hydrophobicity. Here also, the maximum collapse rate is greatest for
      the most hydrophobic polymer. This domination of the pH-response kinetics by
      monomer hydrophobicity is attributed to attractive hydrophobic forces between
      polymer segments overcoming the repulsive electrostatic forces between the
      tertiary amine residues. 

PMID- 25559879
TI  - Robust two-dimensional topological insulators in methyl-functionalized bismuth,
      antimony, and lead bilayer films.
AB  - One of the major obstacles to a wide application range of the quantum spin Hall
      (QSH) effect is the lack of suitable QSH insulators with a large bulk gap. By
      means of first-principles calculations including relativistic effects, we predict
      that methyl-functionalized bismuth, antimony, and lead bilayers (Me-Bi, Me-Sb,
      and Me-Pb) are 2D topological insulators (TIs) with protected Dirac type
      topological helical edge states, and thus suitable QSH systems. In addition to
      the explicitly obtained topological edge states, the nontrivial topological
      characteristic of these systems is confirmed by the calculated nontrivial Z2
      topological invariant. The TI characteristics are intrinsic to the studied
      materials and are not subject to lateral quantum confinement at edges, as
      confirmed by explicit simulation of the corresponding nanoribbons. It is
      worthwhile to point out that the large nontrivial bulk gaps of 0.934 eV (Me-Bi),
      0.386 eV (Me-Sb), and 0.964 eV (Me-Pb) are derived from the strong spin-orbit
      coupling within the p(x) and p(y) orbitals and would be large enough for room
      temperature application. Moreover, we show that the topological properties in
      these three systems are robust against mechanical deformation. These novel 2D TIs
      with such giant topological energy gaps are promising platforms for topological
      phenomena and possible applications at high temperature.

PMID- 25559880
TI  - Recombination as a motor of host switches and virus emergence: geminiviruses as
      case studies.
AB  - Genetic recombination facilitates the transfer of genetic information in a
      parasexual reproduction manner even between distantly related species. Within the
      Geminiviridae family, a group of plant-infecting viruses that severely constrain
      cropping systems worldwide, it is highly suspected that recombination was pivotal
      in the emergence as a devastating phytopathological problem. Whereas extensive
      evidence of recombination suggests that this mechanism might be adaptive in this
      family, direct demonstration remains scarce. Here we assemble lines of evidences
      indicating that recombination was crucial in driving host switches and further
      emergence of geminiviruses, making these viruses such successful plant pathogens.

PMID- 25559881
TI  - The 'emergence' of turnip mosaic virus was probably a 'gene-for-quasi-gene'
      event.
AB  - Turnip mosaic potyvirus is a virus of brassicas that emerged from a lineage of
      monocotyledon-infecting potyviruses about 1000 years ago. In vivo and in silico
      studies all indicate that sites, primarily in its protein 3 (P3) and cylindrical
      inclusion protein (CI) genes, but also its small 6 kDa 2 protein (6K2) and genome
      linked viral protein (VPg) genes, control host specificity in a dynamic way. It
      is most likely that non-unique combinations of transient viral genomic single
      nucleotide polymorphisms (SNPs), not all of them non-synonymous, allowed the host
      switch to occur. These SNPs were probably ephemeral and replaced over time by
      other combinations as the population subsequently diverged within, and adapted
      to, the brassica host population.

PMID- 25559883
TI  - Association of cerebrospinal fluid prion protein levels and the distinction
      between Alzheimer disease and Creutzfeldt-Jakob disease.
AB  - IMPORTANCE: Although typical forms of Alzheimer disease (AD) and Creutzfeldt
      Jakob disease (CJD) are clinically distinguishable, atypical AD phenotypes may
      pose a diagnostic challenge. The major biological diagnostic biomarker for
      identifying CJD, 14-3-3 protein in cerebrospinal fluid (CSF), unfortunately lacks
      specificity when confronting a rapid dementia presentation. OBJECTIVE: To assess
      the relevance of total CSF prion protein (t-PrP) levels in the differential
      biological diagnosis between atypical AD phenotypes and CJD. DESIGN, SETTING, AND
      PARTICIPANTS: A retrospective study in an autopsy-confirmed cohort of 82 patients
      was performed to evaluate the relevance of CSF t-PrP to distinguish 30 definite
      cases of AD from 52 definite cases of CJD. Next, CSF t-PrP concentration was
      measured in a cohort of 104 patients including 55 patients with probable AD, 26
      with probable sporadic CJD, and 23 control patients for whom 14-3-3 protein,
      total tau, phosphorylated tau 181 (P-tau181), and Abeta1-42 were available. We
      investigated 46 patients diagnosed as having probable AD who presented atypical
      phenotypes. A diagnosis strategy was proposed to classify atypical AD phenotypes
      with suspicion of CJD based on a decision tree combining CSF biomarkers. MAIN
      OUTCOMES AND MEASURES: We determined CSF t-PrP levels for all patients. We
      calculated the ratio of total tau and P-tau181 and determined the diagnostic
      accuracy of each biomarker alone or in combination. We calculated the
      misclassification rate for each biomarker that corresponded to the percentage of
      patients within the group of atypical AD phenotypes wrongly classified as CJD.
      RESULTS: In patients with CJD, CSF t-PrP concentrations were decreased compared
      with control participants and patients with AD. When considering the differential
      diagnosis of CJD compared with atypical AD phenotypes, CSF t-PrP determination
      reached 82.1% sensitivity and 91.3% specificity. The misclassification rate of
      atypical AD phenotypes decreased from 43.5%, obtained when using the CSF 14-3-3
      protein determination alone, to only 4.3% when calculating the ratio total tau/(P
      tau181 * t-PrP). The proposed classification tree permitted correct
      classification of 98.4% of the patients. CONCLUSIONS AND RELEVANCE: For unusual
      phenotypes of AD, especially cases presenting with a biological ambiguity
      suggesting CJD, determination of CSF t-PrP levels increased diagnostic accuracy.
      The use of CSF t-PrP levels may be beneficial in clinical practice in addition to
      the current classic biomarkers.

PMID- 25559882
TI  - Sodium butyrate epigenetically modulates high-fat diet-induced skeletal muscle
      mitochondrial adaptation, obesity and insulin resistance through nucleosome
      positioning.
AB  - BACKGROUND AND PURPOSE: Sodium butyrate (NaB), an epigenetic modifier, is
      effective in promoting insulin sensitivity. The specific genomic loci and
      mechanisms underlying epigenetically induced obesity and insulin resistance and
      the targets of NaB are not fully understood. EXPERIMENTAL APPROACH: The anti
      diabetic and anti-obesity effects of NaB treatment were measured by comparing
      phenotypes and physiologies of C57BL/6J mice fed a low-fat diet (LF), high-fat
      diet (HF) or high-fat diet plus NaB (HF + NaB) for 10 weeks. We determined a
      possible mechanism of NaB action through induction of beneficial skeletal muscle
      mitochondrial adaptations and applied microccocal nuclease digestion with
      sequencing (MNase-seq) to assess whole genome differences in nucleosome occupancy
      or positioning and to identify associated epigenetic targets of NaB. KEY RESULTS:
      NaB prevented HF diet-induced increases in body weight and adiposity without
      altering food intake or energy expenditure, improved insulin sensitivity as
      measured by glucose and insulin tolerance tests, and decreased respiratory
      exchange ratio. In skeletal muscle, NaB increased the percentage of type 1
      fibres, improved acylcarnitine profiles as measured by metabolomics and produced
      a chromatin structure, determined by MNase-seq, similar to that seen in LF.
      Targeted analysis of representative nuclear-encoded mitochondrial genes showed
      specific repositioning of the -1 nucleosome in association with altered gene
      expression. CONCLUSIONS AND IMPLICATIONS: NaB treatment may be an effective
      pharmacological approach for type 2 diabetes and obesity by inducing -1
      nucleosome repositioning within nuclear-encoded mitochondrial genes, causing
      skeletal muscle mitochondrial adaptations that result in more complete beta
      oxidation and a lean, insulin sensitive phenotype.

PMID- 25559884
TI  - Theoretical study on carbon-carbon short contact of ~2.3 A: intermediate state
      between nonbonding and sigma-covalent bonding.
AB  - An unusual intermolecular carbon-carbon short contact, observed previously in the
      crystal structure of the copper complex of pyridoxal-5-phosphate- pyridoxamine-5
      phospate Schiff base, was investigated from a standpoint of quantum chemistry by
      DFT calculations with plane wave basis sets. The DFT-optimized structure
      qualitatively reproduced the short contact (2.6-2.8 A) of the intermolecular
      carbon-carbon pairs for the dimer of the copper complexes in the unit cell,
      compared to that (~2.3 A) of the X-ray diffraction data. By the occupied and
      unoccupied orbitals, the dimer showed the in-phase and out-of-phase interactions
      along the direction of the intermolecular distance. The dimer of the copper
      complexes was confirmed as the stable intermediate between nonbonding and sigma
      covalent bonding by the electronic energy curve along the distance of the
      monomers. 

PMID- 25559885
TI  - Overtubes and fluoroscopy for direct percutaneous endoscopic jejunostomy: useful,
      although not always needful and sometimes harmful.

PMID- 25559886
TI  - Moderating effect of self-efficacy on the relation between behavior problems in
      persons with dementia and the distress they cause in caregivers.
AB  - INTRODUCTION: Behavioral and psychological symptoms in dementia (BPSD) are the
      principal sources of stress in caregivers. The aim of the present work is to
      analyze the moderating effect of self-efficacy for managing BPSD on the distress
      these problems generate in family caregivers. METHOD: The participants were 231
      family caregivers of people with dementia. We assessed the frequency and
      caregiver distress associated with three dimensions of BPSD (depressive,
      disruptive and memory problems). In addition, we assessed the moderating effect
      of self-efficacy for dealing with BPSD in the relationship between the dementia
      patient's frequency of BPSD and caregiver distress through hierarchical
      regression analyses, one for each of the dimensions of BPSD. RESULTS: We found a
      moderating effect of self-efficacy on the relation between the frequency of BPSD
      and the distress in caregivers for the dimensions of depressive and disruptive
      behaviors. Caregivers having to deal with a high frequency of behavior problems
      but with high levels of self-efficacy presented significantly lower levels of
      distress associated with depressive and disruptive behavior problems compared to
      those caregivers with low levels of self-efficacy. No differences in the effects
      of self-efficacy were found for distress levels of caregivers who dealt with low
      frequency of BPSD. Also, we did not find a moderating effect of self-efficacy on
      the relation between the frequency of memory problems and caregivers' distress.
      CONCLUSIONS: The results suggest that self-efficacy for managing BPSD attenuates
      the relation between the frequency of behavior problems - both disruptive and
      depressive - and the distress they cause in caregivers.

PMID- 25559888
TI  - Can chemoradiation allow for omission of lateral pelvic node dissection for
      locally advanced rectal cancer?
AB  - OBJECTIVES: We evaluated the relationship between pretreatment clinical
      parameters and lateral pelvic node (LPN) recurrence in patients with rectal
      cancer treated with a combination of curative resection and chemoradiotherapy
      (CRT) and attempted to identify the patients who might benefit from LPN
      dissection. METHODS: This study involved 900 patients between June 2001 and June
      2009. Pretreatment clinical parameters including radiological size of LPN were
      analyzed to identify risk factors associated with long-term outcomes. RESULTS:
      Locoregional recurrence developed in 65 patients (7.2%); 42 (64.6%) had LPN
      recurrence, 20 (47.6%) of which had no distant metastasis. Multivariate analysis
      showed that LPN short-axis diameter (<5, 5-<10, and >=10 mm) was significantly
      associated with LPN recurrence-free survival (5-year survival rate (5YSR), 98.2,
      91.7, and 40.1%, respectively, P < 0.05), locoregional recurrence-free survival
      (5YSR, 95.5, 87.6, and 40.1%, respectively, P < 0.05), relapse-free survival
      (5YSR, 76.8, 72.5, and 30.3, respectively, P < 0.05), and overall survival (5YSR,
      86.3, 83.0, and 57.5%, respectively, P < 0.05). CONCLUSIONS: Patients with an LPN
      short-axis diameter >=10 mm represent a potential subgroup at a high risk of LPN
      recurrence, even after CRT. Further study is needed to confirm whether LPN
      dissection is beneficial for these patients.

PMID- 25559887
TI  - Acute administration of n-3 rich triglyceride emulsions provides cardioprotection
      in murine models after ischemia-reperfusion.
AB  - Dietary n-3 fatty acids (FAs) may reduce cardiovascular disease risk. We
      questioned whether acute administration of n-3 rich triglyceride (TG) emulsions
      could preserve cardiac function and decrease injury after ischemia/reperfusion
      (I/R) insult. We used two different experimental models: in vivo, C57BL/6 mice
      were exposed to acute occlusion of the left anterior descending coronary artery
      (LAD), and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff
      technique (LT). In the LAD model, mice treated with n-3 TG emulsion (1.5 g/kg
      body weight), immediately after ischemia and 1 h later during reperfusion,
      significantly reduced infarct size and maintained cardiac function (p<0.05). In
      the LT model, administration of n-3 TG emulsion (300 mg TG/100 ml) during
      reperfusion significantly improved functional recovery (p<0.05). In both models,
      lactate dehydrogenase (LDH) levels, as a marker of injury, were significantly
      reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs
      protects hearts from I/R injury, we investigated changes in key pathways linked
      to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased
      phosphorylation of AKT and GSK3beta proteins (p<0.05). Acute n-3 TG emulsion
      treatment also increased Bcl-2 protein level and reduced an autophagy marker,
      Beclin-1 (p<0.05). Additionally, cardioprotection by n-3 TG emulsion was linked
      to changes in PPARgamma protein expression (p<0.05). Rosiglitazone and p-AKT
      inhibitor counteracted the positive effect of n-3 TG; GSK3beta inhibitor plus n-3
      TG significantly inhibited LDH release. We conclude that acute n-3 TG injection
      during reperfusion provides cardioprotection. This may prove to be a novel acute
      adjunctive reperfusion therapy after treating patients with myocardial
      infarction.

PMID- 25559889
TI  - Inverse consistent non-rigid image registration based on robust point set
      matching.
AB  - BACKGROUND: Robust point matching (RPM) has been extensively used in non-rigid
      registration of images to robustly register two sets of image points. However,
      except for the location at control points, RPM cannot estimate the consistent
      correspondence between two images because RPM is a unidirectional image matching
      approach. Therefore, it is an important issue to make an improvement in image
      registration based on RPM. METHODS: In our work, a consistent image registration
      approach based on the point sets matching is proposed to incorporate the property
      of inverse consistency and improve registration accuracy. Instead of only
      estimating the forward transformation between the source point sets and the
      target point sets in state-of-the-art RPM algorithms, the forward and backward
      transformations between two point sets are estimated concurrently in our
      algorithm. The inverse consistency constraints are introduced to the cost
      function of RPM and the fuzzy correspondences between two point sets are
      estimated based on both the forward and backward transformations simultaneously.
      A modified consistent landmark thin-plate spline registration is discussed in
      detail to find the forward and backward transformations during the optimization
      of RPM. The similarity of image content is also incorporated into point matching
      in order to improve image matching. RESULTS: Synthetic data sets, medical images
      are employed to demonstrate and validate the performance of our approach. The
      inverse consistent errors of our algorithm are smaller than RPM. Especially, the
      topology of transformations is preserved well for our algorithm for the large
      deformation between point sets. Moreover, the distance errors of our algorithm
      are similar to that of RPM, and they maintain a downward trend as whole, which
      demonstrates the convergence of our algorithm. The registration errors for image
      registrations are evaluated also. Again, our algorithm achieves the lower
      registration errors in same iteration number. The determinant of the Jacobian
      matrix of the deformation field is used to analyse the smoothness of the forward
      and backward transformations. The forward and backward transformations estimated
      by our algorithm are smooth for small deformation. For registration of lung
      slices and individual brain slices, large or small determinant of the Jacobian
      matrix of the deformation fields are observed. CONCLUSIONS: Results indicate the
      improvement of the proposed algorithm in bi-directional image registration and
      the decrease of the inverse consistent errors of the forward and the reverse
      transformations between two images.

PMID- 25559890
TI  - Importance of the node of Calot in gallbladder neck dissection: an important
      landmark in the standardized approach to the laparoscopic cholecystectomy.
AB  - The current rate of bile duct injury (BDI) after laparoscopic cholecystectomy is
      0.4%, which is an unacceptable outcome. Several surgical approaches have been
      suggested to mitigate the occurrence of this dreaded complication. We propose a
      standardized approach, using Calot's node as a critical anatomical landmark to
      guide gallbladder dissection and avoid BDI. We retrospectively analyzed a
      prospectively gathered database of 907 laparoscopic cholecystectomies using this
      standardized approach in our practice over a 5-year period. To date we have had
      no BDI and no cystic duct leak. Therefore, we suggest identification of Calot's
      node as an additional method to avoid BDI during laparoscopic cholecystectomy. 

PMID- 25559891
TI  - Chitosan nanoparticles for the linear release of model cationic Peptide.
AB  - PURPOSE: The present study is focused on the development of a model drug delivery
      system (DDS) based on Chitosan (CS) nanoparticles using Renin substrate I (RSI)
      as model agent. RSI shares the main chemical-physical features of several
      biologically active antimicrobial peptides (AMPs). AMPs have a great therapeutic
      potential that is hampered by their lability in the biological fluids and as such
      they are perfect candidates for DDS. The development studies of quality DDS
      loaded with AMPs would require highly sensitive and specific quantification
      assays. The use of RSI allowed for the fine-tuning and optimization of the
      formulation parameters to promote the hydrophobic interactions between CS and the
      cationic peptide, favour the loading of the active ingredient and enhance the
      release properties of the carrier. METHODS: RSI was encapsulated in chitosan NPs
      by mean of ionic gelation and a chromogenic enzymatic essay was carried out for
      the release kinetics evaluation. RESULTS: The developed formulations displayed
      almost 100% of encapsulation efficacy, low burst percentages, and a linear
      release of the model peptide. A release model was created showing a direct
      dependence on both the amount of RSI and NPs radius. CONCLUSIONS: Although CS has
      always been formulated with negatively charged active agents (e.g.
      oligonucleotides or anionic proteins), the use of ionotropic gelation in presence
      of a small cationic active agent promoted the formation of "core-shell" NPs. The
      described model, with tuneable linear release rates, appears eligible for further
      exploitation such as the loading of therapeutically active AMPs.

PMID- 25559892
TI  - MD-2 is required for disulfide HMGB1-dependent TLR4 signaling.
AB  - Innate immune receptors for pathogen- and damage-associated molecular patterns
      (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury.
      Secreted by activated immune cells or passively released by damaged cells, HMGB1
      is subjected to redox modification that distinctly influences its extracellular
      functions. Previously, it was unknown how the TLR4 signalosome distinguished
      between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor,
      myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine
      inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD
      2-deficient mice, as well as MD-2 silencing in macrophages, we show a requirement
      for HMGB1-dependent TLR4 signaling. By screening HMGB1 peptide libraries, we
      identified a tetramer (FSSE, designated P5779) as a specific MD-2 antagonist
      preventing MD-2-HMGB1 interaction and TLR4 signaling. P5779 does not interfere
      with lipopolysaccharide-induced cytokine/chemokine production, thus preserving
      PAMP-mediated TLR4-MD-2 responses. Furthermore, P5779 can protect mice against
      hepatic ischemia/reperfusion injury, chemical toxicity, and sepsis. These
      findings reveal a novel mechanism by which innate systems selectively recognize
      specific HMGB1 isoforms. The results may direct toward strategies aimed at
      attenuating DAMP-mediated inflammation while preserving antimicrobial immune
      responsiveness. 

PMID- 25559894
TI  - Mechanism for the antibacterial action of epigallocatechin gallate (EGCg) on
      Bacillus subtilis.
AB  - Catechins are a class of polyphenols and have high anti-bacterial activity
      against various microorganisms. Here, we report the mechanism for antibacterial
      activity of epigallocatechin gallate (EGCg) against Gram-positive bacteria
      Bacillus subtilis, which is highly sensitive to EGCg. Transmission electron
      microscope analysis revealed that deposits containing EGCg were found throughout
      the cell envelope from the outermost surface to the outer surface of cytoplasmic
      membrane. Aggregating forms of proteins and EGCg were identified as spots that
      disappeared or showed markedly decreased intensity after the treatment with EGCg
      compared to the control by two-dimensional electrophoresis. Among the identified
      proteins included 4 cell surface proteins, such as oligopeptide ABC transporter
      binding lipoprotein, glucose phosphotransferase system transporter protein,
      phosphate ABC transporter substrate-binding protein, and penicillin-binding
      protein 5. Observations of glucose uptake of cells and cell shape B. subtilis
      after the treatment with EGCg suggested that EGCg inhibits the major functions of
      these proteins, leading to growth inhibition of B. subtilis. 

PMID- 25559895
TI  - Understanding the feasibility of integrating the eating disorders and obesity
      fields: the beyond obesity and disordered eating in youth (BODY) Study.
AB  - BACKGROUND: Attention has been devoted to exploring ways to integrate the eating
      disorders (ED) and obesity (OB) prevention fields. Although research has revealed
      considerable overlap between the risk factors for ED and those for OB,
      collaboration between the two fields remains strained. Existing position papers
      focus mainly on discussions about the lack of collaboration and whether or not
      the two fields should merge their prevention efforts. However, no empirical study
      has yet addressed these questions. The beyond obesity and disordered eating in
      youth (BODY) Study is a qualitative study that sheds light on the relationship
      between the ED and OB fields. AIM: Using part of the BODY Study data and
      findings, this paper aims to further explore the costs and benefits of ED and OB
      collaboration/integration. Four models, or scenarios, proposed by Neumark
      Sztainer to describe the interaction between the ED and OB prevention fields are
      used as a framework to guide the BODY Study findings' discussion. METHOD: Based
      on grounded theory methodology, the BODY Study used in-depth interviews and focus
      groups as data collection methods. A total of 61 participants took part in the
      study: 35 researchers/practitioners who work in either ED or OB; and 26 youths
      (aged 16-26 who attended six focus groups and 12 in-depth interviews). ANALYSIS:
      Selected BODY Study themes, relevant to better understanding the four scenarios
      proposed by Neumark-Sztainer, presented in this paper are: (a) Two camps:
      understanding the relationship between the ED and OB fields; (b) Consequences for
      professionals and youths of the existence of two camps; (c) Root causes of the
      perceived tension: ideology and philosophy, power and knowledge, and gender.
      CONCLUSION: Findings from this study mirror existing theoretical papers that look
      at the relationship between the two fields-including Neumark-Sztainer's
      scenarios. At the same time, this empirical work further discusses the costs of a
      possible integration that, even if desirable, does not take into account the root
      causes of the tension between the two fields (e.g., power imbalance, gender
      neutrality).

PMID- 25559893
TI  - Neutrophil-related factors as biomarkers in EAE and MS.
AB  - A major function of T helper (Th) 17 cells is to induce the production of factors
      that activate and mobilize neutrophils. Although Th17 cells have been implicated
      in the pathogenesis of multiple sclerosis (MS) and the animal model experimental
      autoimmune encephalomyelitis (EAE), little attention has been focused on the role
      of granulocytes in those disorders. We show that neutrophils, as well as
      monocytes, expand in the bone marrow and accumulate in the circulation before the
      clinical onset of EAE, in response to systemic up-regulation of granulocyte
      colony-stimulating factor (G-CSF) and the ELR(+) CXC chemokine CXCL1. Neutrophils
      comprised a relatively high percentage of leukocytes infiltrating the central
      nervous system (CNS) early in disease development. G-CSF receptor deficiency and
      CXCL1 blockade suppressed myeloid cell accumulation in the blood and ameliorated
      the clinical course of mice that were injected with myelin-reactive Th17 cells.
      In relapsing MS patients, plasma levels of CXCL5, another ELR(+) CXC chemokine,
      were elevated during acute lesion formation. Systemic expression of CXCL1, CXCL5,
      and neutrophil elastase correlated with measures of MS lesion burden and clinical
      disability. Based on these results, we advocate that neutrophil-related molecules
      be further investigated as novel biomarkers and therapeutic targets in MS. 

PMID- 25559897
TI  - Porocarcinoma coexisting at a site of Bowen disease in a 63-year-old woman.
AB  - Porocarcinoma is an unusual, locally aggressive and potentially fatal neoplasm.
      Several cutaneous malignancies have been described in association with
      porocarcinoma, including squamous cell carcinoma, basal cell carcinoma and
      tricholemmal carcinoma. Previous reports have indicated that the occurrence of
      malignant tumours in combination with porocarcinoma is extremely rare, in
      particular with regard to Bowen disease (BD). We report an uncommon case of
      porocarcinoma occurring synchronously in a single BD lesion in a 63-year-old
      woman with multiple BD lesions. The clinical and histological findings confirmed
      this diagnosis. 

PMID- 25559896
TI  - pH-controlled gas-generating mineralized nanoparticles: a theranostic agent for
      ultrasound imaging and therapy of cancers.
AB  - We report a theranostic nanoparticle that can express ultrasound (US) imaging and
      simultaneous therapeutic functions for cancer treatment. We developed doxorubicin
      loaded calcium carbonate (CaCO3) hybrid nanoparticles (DOX-CaCO3-MNPs) through a
      block copolymer templated in situ mineralization approach. The nanoparticles
      exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide
      (CO2) bubbles and showed excellent echo persistence. In vivo results demonstrated
      that the DOX-CaCO3-MNPs generated CO2 bubbles at tumor tissues sufficient for
      echogenic reflectivity under a US field. In contrast, the DOX-CaCO3-MNPs located
      in the liver or tumor-free subcutaneous area did not generate the CO2 bubbles
      necessary for US contrast. The DOX-CaCO3-MNPs could also trigger the DOX release
      simultaneously with CO2 bubble generation at the acidic tumoral environment. The
      DOX-CaCO3-MNPs displayed effective antitumor therapeutic activity in tumor
      bearing mice. The concept described in this work may serve as a useful guide for
      development of various theranostic nanoparticles for US imaging and therapy of
      various cancers. 

PMID- 25559898
TI  - Inborn errors of ketone body utilization.
AB  - Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency and mitochondrial
      acetoacetyl-CoA thiolase (beta-ketothiolase or T2) deficiency are classified as
      autosomal recessive disorders of ketone body utilization characterized by
      intermittent ketoacidosis. Patients with mutations retaining no residual activity
      on analysis of expression of mutant cDNA are designated as severe genotype, and
      patients with at least one mutation retaining significant residual activity, as
      mild genotype. Permanent ketosis is a pathognomonic characteristic of SCOT
      deficient patients with severe genotype. Patients with mild genotype, however,
      may not have permanent ketosis, although they may develop severe ketoacidotic
      episodes similar to patients with severe genotype. Permanent ketosis has not been
      reported in T2 deficiency. In T2-deficient patients with severe genotype,
      biochemical diagnosis is done on urinary organic acid analysis and blood
      acylcarnitine analysis to observe characteristic findings during both
      ketoacidosis and non-episodic conditions. In Japan, however, it was found that T2
      deficient patients with mild genotype are common, and typical profiles were not
      identified on these analyses. Based on a clinical study of ketone body
      utilization disorders both in Japan and worldwide, we have developed guidelines
      for disease diagnosis and treatment. These diseases are treatable by avoiding
      fasting and by providing early infusion of glucose, which enable the patients to
      grow without sequelae. 

PMID- 25559900
TI  - Comparison of Physical and Physiological Profiles in Elite and Amateur Young
      Wrestlers.
AB  - The aim of this study is to examine the physical and physiological determinants
      of wrestling success between elite and amateur male wrestlers. The wrestlers (N =
      126) were first assigned to 3 groups based on their competitive level (top elite,
      elite, and amateur) and then to 6 groups according to their body mass (light,
      middle, and heavy weight) and their competitive level (elite and amateur). Top
      elite and elite wrestlers had significantly (p <= 0.05) more training experiences
      and maximal oxygen uptake compared with the amateur group. In separating weight
      classes, light- and middle-weight elite (MWE) wrestlers had significantly (p <=
      0.05) more training experience (7-20%) compared with the light- and middle-weight
      amateur (MWA) wrestlers. No significant differences were detected between elite
      and amateur groups (light-, middle-, and heavy-weight wrestlers) for age, body
      mass, height, body mass index, and body fat (p > 0.05), with the exception of
      height for heavy wrestlers. Leg average and peak power values (in watts and watts
      per kilogram) in MWE were higher than MWA (6.5 and 13%, p <= 0.05). Relative leg
      average power value in heavy-weight elite (HWE) (in watts per kilogram) was
      higher than heavy-weight amateur (HWA) (9.6%, p <= 0.05). It was seen that elite
      wrestlers in MWE and HWE statistically possessed a higher VO2max (12.5 and 11.4%,
      respectively) than amateur middle- and heavy-weight wrestlers (p <= 0.05). The
      results of this study suggest that training experience, aerobic endurance, and
      anaerobic power and capacity will give a clear advantage for the wrestlers to
      take part in the elite group.

PMID- 25559899
TI  - Which Patients With Low Back Pain Benefit From Deadlift Training?
AB  - Recent studies have indicated that the deadlift exercise may be effective in
      decreasing pain intensity and increasing activity for most, but not all, patients
      with a dominating pattern of mechanical low back pain. This study aimed to
      evaluate which individual factors measured at baseline could predict activity,
      disability, and pain intensity in patients with mechanical low back pain after an
      8-week training period involving the deadlift as a rehabilitative exercise.
      Thirty-five participants performed deadlift training under the supervision of a
      physical therapist with powerlifting experience. Measures of pain-related fear of
      movement, hip and trunk muscle endurance, and lumbopelvic movement control were
      collected at baseline. Measures of activity, disability, and pain intensity were
      collected at baseline and at follow-up. Linear regression analyses were used to
      create models to predict activity, disability, and pain intensity at follow-up.
      Results showed that participants with less disability, less pain intensity, and
      higher performance on the Biering-Sorensen test, which tests the endurance of hip
      and back extensor muscles, at baseline benefit from deadlift training. The
      Biering-Sorensen test was the most robust predictor because it was included in
      all predictive models. Pain intensity was the next best predictor as it was
      included in 2 predictive models. Thus, for strength and conditioning
      professionals who use the deadlift as a rehabilitative exercise for individuals
      with mechanical low back pain, it is important to ensure that clients have
      sufficient back extensor strength and endurance and a sufficiently low pain
      intensity level to benefit from training involving the deadlift exercise.

PMID- 25559901
TI  - Multiple Transportable Carbohydrates During Exercise: Current Limitations and
      Directions for Future Research.
AB  - The concept of multiple transportable carbohydrates (MTC) refers to a combination
      of saccharides that rely on distinct transporters for intestinal absorption.
      Ingestion of MTC during prolonged exercise has been purported to increase
      carbohydrate absorption efficiency, increase exogenous carbohydrate oxidation,
      reduce gastrointestinal (GI) distress, and improve athletic performance when
      carbohydrate intake is high (>50-60 g.h-1). Although reviews of MTC research have
      been published previously, a comprehensive literature evaluation underscoring
      methodological limitations has not been conducted to guide future work.
      Accordingly, this review outlined the plausible mechanisms of MTC and
      subsequently evaluated MTC research based on several factors, including
      participant characteristics, exercise modality, exercise task, treatment
      formulation, treatment blinding, and pre-exercise nutrition status. A total of 27
      articles examining MTC during exercise were identified and reviewed. Overall,
      ingestion of MTC led to increased exogenous carbohydrate oxidation, reduced GI
      distress, and improved performance during cycling lasting >=2.5 hours,
      particularly when carbohydrate was ingested at >=1.2 g.min-1. Despite the
      apparent benefits, several limitations in the literature were apparent, including
      that only 3 studies used running, only 2 studies were conducted in the field,
      most participants were fasted, and women and adolescents were underrepresented.
      In addition, the majority of the studies fed carbohydrate at >=1.2 g.min-1, which
      may have inflated levels of GI distress and exaggerated performance decrements
      with single-saccharide feedings. Based on these limitations, future MTC
      investigations should consider focusing on running, examining team-based sports,
      including women and adolescents, conducting experiments under field conditions,
      examining the modifying effects of pre-exercise nutrition, and using modest
      feeding protocols (1.0-1.2 g.min-1).

PMID- 25559902
TI  - Brazilian Jiu-Jitsu Simulated Competition Part II: Physical Performance, Time
      Motion, Technical-Tactical Analyses, and Perceptual Responses.
AB  - The aim of this study was to analyze performance, time structure, technical
      actions, and perceptual responses in Brazilian jiu-jitsu athletes during a
      simulated competition. For this purpose, 10 athletes were analyzed in a simulated
      competition (4 matches of 10 minutes). Physical tests and scales of the
      perception of effort and recovery were applied. The matches were recorded for the
      purpose of technical-tactical analysis and to determine the time structure. The
      main results show that in the simulated competition, reaction time (F(2.5,17.6) =
      2.7; p = 0.087; eta2 = 0.28) and flexibility (F(7,63) = 1.5; p = 0.172; eta2 =
      0.15) were unchanged across the matches. An analysis of variance showed a
      significant difference for grip endurance using the kimono (F(2.0,15.9) = 8.1; p
      = 0.004; eta2 = 0.50), which was not confirmed by the Bonferroni test. Jump
      height indicated postactivation potentiation after match 2 (F(7,63) = 3.5; p =
      0.003; eta2 = 0.28). The maximal isometric handgrip strength in the dominant hand
      (F(3.2,28.6) = 2.9; p = 0.049; eta2 = 0.24) and in the nondominant hand (F(7,63)
      = 3.8; p = 0.002; eta2 = 0.30) showed a decline after matches 3 and 4. Although
      these data indicate the onset of fatigue, the effort/pause ratio of the matches
      was not altered (F(3,12) = 0.6; p = 0.624; eta2 = 0.13). The perceptions of
      effort (F(3,27) = 0.9; p = 0.469; eta2 = 0.09) and recovery (F(1.9,17.0) = 2.4; p
      = 0.125; eta2 = 0.21) and the degree of fatigue reported (F(1.5,13.8) = 0.5; p =
      0.588; eta2 = 0.05) did not change during the simulated competition. Thus, it may
      be concluded that the execution of successive matches causes a decline in maximal
      isometric handgrip strength. No changes in the time structure of the matches or
      in the perceptual responses were observed.

PMID- 25559903
TI  - Effect of Vertical, Horizontal, and Combined Plyometric Training on Explosive,
      Balance, and Endurance Performance of Young Soccer Players.
AB  - The aim of this study was to compare the effects of 6 weeks of vertical,
      horizontal, or combined vertical and horizontal plyometric training on muscle
      explosive, endurance, and balance performance. Forty young soccer players aged
      between 10 and 14 years were randomly divided into control (CG; n = 10), vertical
      plyometric group (VG; n = 10), horizontal plyometric group (HG; n = 10), and
      combined vertical and horizontal plyometric group (VHG; n = 10). Players
      performance in the vertical and horizontal countermovement jump with arms, 5
      multiple bounds test (MB5), 20-cm drop jump reactive strength index (RSI20),
      maximal kicking velocity (MKV), sprint, change of direction speed (CODS), Yo-Yo
      intermittent recovery level 1 test (Yo-Yo IR1), and balance was measured. No
      significant or meaningful changes in the CG, apart from small change in the Yo-Yo
      IR1, were observed while all training programs resulted in meaningful changes in
      explosive, endurance, and balance performance. However, only VHG showed a
      statistically significant (p <= 0.05) increase in all performance test and most
      meaningful training effect difference with the CG across tests. Although no
      significant differences in performance changes were observed between experimental
      groups, the VHG program was more effective compared with VG (i.e., jumps, MKV,
      sprint, CODS, and balance performance) and HG (i.e., sprint, CODS, and balance
      performance) to small effect. The study demonstrated that vertical, horizontal,
      and combined vertical and horizontal jumps induced meaningful improvement in
      explosive actions, balance, and intermittent endurance capacity. However,
      combining vertical and horizontal drills seems more advantageous to induce
      greater performance improvements.

PMID- 25559904
TI  - Reductions in Sprint Paddling Ability and Countermovement Jump Performance After
      Surfing Training.
AB  - The present study aimed to determine whether any meaningful change in a surfer's
      sprint paddling ability and countermovement jump (CMJ) performance developed
      after a 2-hour surfing training session and also whether any physical demands of
      the surfing session were related to the resultant changes in the capacities.
      Fifteen competitive male surfing athletes (age, 22.1 +/- 3.9 years; height, 175.4
      +/- 6.4 cm; body mass, 72.5 +/- 7.7 kg) performed a 2-hour surfing training
      session, with 15-m sprint paddle and CMJ trials performed both before and after
      the surfing session. Pre- to posttesting measures were analyzed using magnitude
      based inferences. Likely declines were observed in the velocity achieved at the 5
      , 10-, and 15-m splits of the 15-m sprint paddle, as well as peak velocity.
      Similarly, likely declines were calculated for CMJ peak force, relative peak
      force, and jump height. Furthermore, large correlations were calculated between
      presurfing session peak velocity and the change in 5, 10, 15 m, and peak velocity
      of the 15-m sprint paddle and total distance covered, wave riding bouts, and
      success rate. Surfing athletes and coaches may need to consider implementing
      shorter duration training sessions to reduce the decline in sprint paddling
      ability and CMJ performance. Furthermore, surfing athletes should possess highly
      developed sprint paddling ability because this may allow them to undertake a
      greater workload and catch more waves, which will increase the opportunity for
      technical refinement of maneuvers and skill acquisition.

PMID- 25559905
TI  - Effect of Progressive Volume-Based Overload During Plyometric Training on
      Explosive and Endurance Performance in Young Soccer Players.
AB  - The purpose of the study was to compare the effects of progressive volume-based
      overload with constant volume-based overload on muscle explosive and endurance
      performance adaptations during a biweekly short-term (i.e., 6 weeks) plyometric
      training intervention in young soccer players. Three groups of young soccer
      players (age 13.0 +/- 2.3 years) were divided into: control (CG; n = 8) and
      plyometric training with (PPT; n = 8) and without (NPPT; n = 8) a progressive
      increase in volume (i.e., 16 jumps per leg per week, with an initial volume of 80
      jumps per leg each session). Bilateral and unilateral horizontal and vertical
      countermovement jump with arms (CMJA), 20-cm drop jump reactive strength index
      (RSI20), maximal kicking velocity (MKV), 10-m sprint, change of direction speed
      (CODS), and Yo-Yo intermittent recovery level 1 test (Yo-Yo IR1) were measured.
      Although both experimental groups significantly increased CMJA, RSI20, CODS, and
      endurance performance, only PPT showed a significant improvement in MKV and 10-m
      sprint time. In addition, only PPT showed a significantly higher performance
      improvement in jumping, MKV, and Yo-Yo IR1 compared with CG. Also, PPT showed
      higher meaningful improvement compared with NPPT in all (except 1) jump
      performance measures. Furthermore, although PPT involved a higher total volume
      compared with NPPT, training efficiency (i.e., percentage change in
      performance/total jump volume) was similar between groups. Our results show that
      PPT and NPPT ensured significant improvement in muscle explosive and endurance
      performance measures. However, a progressive increase in plyometric training
      volume seems more advantageous to induce soccer-specific performance
      improvements.

PMID- 25559906
TI  - Water-Based Concurrent Training Improves Peak Oxygen Uptake, Rate of Force
      Development, Jump Height, and Neuromuscular Economy in Young Women.
AB  - The study investigated the effects of different intrasession exercise sequences
      on the cardiorespiratory and neuromuscular adaptations induced by water-based
      concurrent training in young subjects. Twenty-six healthy young women (25.1 +/-
      2.9 years) were placed into 2 water-based concurrent training groups: resistance
      before (RA, n = 13) or after (AR, n = 13) aerobic training. Subjects trained
      resistance and aerobic training during 12 weeks, 2 times per week performing both
      exercise types in the same training session. Peak oxygen uptake (V[Combining Dot
      Above]O2peak), rate of force development (RFD) obtained during an isometric peak
      torque knee extension protocol, jump height, and neuromuscular economy
      (normalized electromyography at 80% of pretraining knee extension isometric peak
      torque) in young women were determined. After training, there was a significant
      increase (p < 0.001) in both RA and AR in the V[Combining Dot Above]O2peak, with
      no differences between groups (7 vs. 5%). The maximal isometric knee extension
      RFD showed significant increases (p = 0.003) after training (RA: 19 vs. AR: 30%),
      and both groups presented similar gains. In addition, the countermovement jump
      height also increased (p = 0.034) after training (RA: 5% vs. AR: 6%), with no
      difference between groups. After training, there were significant improvements on
      vastus lateralis (p < 0.001) (RA: -13% vs. AR: -20%) and rectus femoris (p =
      0.025) (RA: -17% vs. AR: -7%) neuromuscular economy, with no difference between
      groups. In conclusion, 12 weeks of water-based concurrent training improved the
      peak oxygen uptake, RFD, jump height, and neuromuscular economy in young women
      independent from the intrasession exercise sequence.

PMID- 25559907
TI  - Ultraendurance cycling in a hot environment: thirst, fluid consumption, and water
      balance.
AB  - The purpose of this field investigation was to identify and clarify factors that
      may be used by strength and conditioning professionals to help athletes drink
      adequately but not excessively during endurance exercise. A universal method to
      accomplish this goal does not exist because the components of water balance
      (i.e., sweat rate, fluid consumed) are different for each athlete and endurance
      events differ greatly. Twenty-six male cyclists (mean +/- SD; age, 41 +/- 8
      years; height, 177 +/- 7 cm; body mass, 81.85 +/- 8.95 kg) completed a summer 164
      km road cycling event in 7.0 +/- 2.1 hours (range, 4.5-10.4 hours). Thirst
      ratings, fluid consumed, indices of hydration status, and body water balance
      (ingested fluid volume - [urine excreted + sweat loss]) were the primary outcome
      variables. Measurements were taken before the event, at designated aid stations
      on the course (52, 97, and 136 km), and at the finish line. Body water balance
      during exercise was not significantly correlated with exercise time on the
      course, height, body mass, or body mass index. Thirst ratings were not
      significantly correlated with any variable. We also observed a wide range of
      total sweat losses (4.9-12.7 L) and total fluid intakes (2.1-10.5 L) during this
      ultraendurance event. Therefore, we recommend that strength and conditioning
      professionals develop an individualized drinking plan for each athlete, by
      calculating sweat rate (milliliter per hour) on the basis of body mass change (in
      kilograms), during field simulations of competition.

PMID- 25559908
TI  - Learning the Hang Power Clean: Kinetic, Kinematic, and Technical Changes in Four
      Weightlifting Naive Athletes.
AB  - The investment in learning required to reach benefit with weightlifting training
      is currently not well understood in elite athletes. The purpose of this
      investigation was to quantify changes in vertical jump power production and
      kinematic variables in hang power clean (HPC) performance during the learning
      process from a naive state in a multiple single-subject research design. Four
      elite athletes undertook HPC learning for approximately 20-30 minutes twice per
      week over a 169-day period. Changes in parameters of vertical power production
      during squat jump (SJ) and countermovement jump (CMJ) were monitored from
      baseline (day 0) and at 3 additional occasions. Hang power clean movement
      kinematics and bar path traces were monitored from day 35 and at 3 additional
      occasions particular to the individual's periodized training plan. Descriptive
      statistics were reported within athletes as mean +/- SD. We observed a 14.1-35.7%
      (SJ) and a -14.4 to 20.5% (CMJ) gain in peak power across the 4 jump testing
      occasions with improvements over the first 4 weeks (SJ: 9.2-32.6%; CMJ: -2.91 to
      20.79%). Changes in HPC movement kinematics and barbell path traces occurred for
      each athlete indicating a more rearward-directed center of pressure over the
      concentric phase, greater double knee bend during the transition phase, decreased
      maximal plantar flexion, and minimal vertical displacement of body mass with HPC
      learning. Considering the minimal investment of 4 weeks to achieve increases in
      vertical power production, the benefits of training with HPC justified the
      associated time costs for these 4 elite athletes.

PMID- 25559909
TI  - An Examination of the Relationship Between Movement Demands and Rating of
      Perceived Exertion in Australian Footballers.
AB  - This study aimed to determine whether a relationship existed between movement
      demands, match events, and perceptual match load, as determined by rating of
      perceived exertion (RPE) in professional Australian footballers. The movement
      variables were collected between 1 and 22 times using global positioning system
      units from 21 players during the 2011 and 2012 Australian Football League
      seasons. A range of movement demands and match events were collected to obtain a
      complete insight into the physical demands and work rates of these athletes.
      These data were separated into the high-load (HL, >=9) and low-load (LL, <=8) RPE
      groups. A Mann-Whitney U-test, independent samples t-test, and effect sizes were
      used to determine whether any differences existed between the 2 groups and the
      size of the difference. The results revealed that the HL groups covered more
      distance, spent more time, and produced more efforts at the high deceleration
      zone (2.4-6.7%). Further, the HL group had more possessions and disposals of the
      football than the LL group (9.2-29.6%). The findings have highlighted the
      importance of monitoring accelerations, decelerations, and instantaneous power
      outputs to obtain a comprehensive insight into the physical demands placed on
      team sport athletes. Furthermore, the results demonstrate that training sessions
      should involve a focus on drills that are composed of both skill development and
      physical stimulus element.

PMID- 25559910
TI  - Creatine Usage and Education of Track and Field Throwers at National Collegiate
      Athletic Association Division I Universities.
AB  - The purpose of this study was to analyze the level of creatine use along with the
      perceived benefits and barriers of creatine use among collegiate athletes who
      participate in throwing events within the sport of track and field. A total of
      258 throwers from National Collegiate Athletic Association Division I
      institutions completed an online survey regarding creatine. The results provided
      baseline levels of creatine use and allowed for the analysis of factors related
      to athletic conference affiliation. Results indicate that creatine use remains to
      be a common (32.7%) practice among throwers with significantly higher levels of
      use among Football Bowl Subdivision (FBS) conference athletes (44.6%) than
      Football Championship Subdivision (FCS) conference athletes (28.8%), chi2 =
      5.505, p = 0.019. The most common reasons for using creatine included a desire to
      improve/increase: strength (83.3%), recovery time (69.0%), and performance
      (60.7%). The most common perceived obstacles included contamination/quality
      control (39.5%), cost (33.3%), inconvenience (16.7%), and cramping (14.3%). A
      desire for additional education and training was noted through an expression of
      interest (55.6%) with significantly higher levels of interest from FBS athletes
      (65.6%) than FCS athletes (52.2%), chi2 = 6.425, p = 0.039. However, the athletic
      departments provide nutritional supplement counseling at only 26.6% of the
      schools. Although the access to full-time nutritionist counsel was available at
      57.3% of the schools, there was a significant difference (chi2 = 9.096, p =
      0.003) between FBS schools (73.7%) and FCS schools (51.7%).

PMID- 25559911
TI  - Reliability of a Cycle Ergometer Peak Power Test in Running-based Team Sport
      Athletes: A Technical Report.
AB  - Given the importance of ensuring athletes train and compete in a nonfatigued
      state, reliable tests are required to regularly monitor fatigue. The purpose of
      this study was to investigate the reliability of a cycle ergometer to measure
      peak power during short maximal sprint cycle efforts in running-based team sport
      athletes. Fourteen professional male Australian rules footballers performed a
      sprint cycle protocol during 3 separate trials, with each trial separated by 7
      days. The protocol consisted of a standardized warm-up, a maximal 6-second sprint
      cycle effort, a 1-minute active recovery, and a second maximal 6-second sprint
      cycle effort. Peak power was recorded as the highest power output of the 2 sprint
      cycle efforts. Absolute peak power (mean +/- SD) was 1502 +/- 202, 1498 +/- 191,
      and 1495 +/- 210 W for trials 1, 2, and 3, respectively. The mean coefficient of
      variation, intraclass correlation coefficient, and SE of measurement for peak
      power between trials was 3.0% (90% confidence intervals [CIs] = 2.5-3.8%), 0.96
      (90% CIs = 0.91-0.98), and 39 W, respectively. The smallest worthwhile change for
      relative peak power was 6.0%, which equated to 1.03 W.kg-1. The cycle ergometer
      sprint test protocol described in this study is highly reliable in elite
      Australian rules footballers and can be used to track meaningful changes in
      performance over time, making it a potentially useful fatigue-monitoring tool.

PMID- 25559912
TI  - Reliability of Maximal Back Squat and Power Clean Performances in Inexperienced
      Athletes.
AB  - The aim of the study was to determine between-session reliability of maximal
      weight lifted during the back squat and power clean, in inexperienced athletes,
      and to identify the smallest detectable difference between sessions. Forty-four
      collegiate athletes (men: n = 32; age: 21.5 +/- 2.0 years; height: 180.0 +/- 6.1
      cm; body mass: 81.01 +/- 7.42 kg; women: n = 12; age: 21.0 +/- 1.9 years; height:
      169.0 +/- 5.2 cm; body mass: 62.90 +/- 7.46 kg) participated in this study. One
      repetition maximum (1RM) back squat and power cleans were each performed twice on
      separate days, 3-5 days apart. Paired samples' t tests revealed no significant
      differences between trial 1 and trial 2 of the power clean (70.55 +/- 24.24 kg,
      71.22 +/- 23.87 kg, p > 0.05, power = 0.99) and the back squat (130.32 +/- 34.05
      kg, 129.82 +/- 34.07 kg, p > 0.05, power = 1.0). No differences in reliability or
      measurement error were observed between men and women. Intraclass correlation
      coefficients (ICCs) demonstrated a high reliability (ICC = 0.997, p < 0.001) for
      between-session 1RM power clean with an R of 0.987; similarly, high reliability
      was observed for between-session back squat performances (ICC = 0.994, p <
      0.001), with an R of 0.978. The smallest detectable difference between sessions
      for both measures were ~5%, highlighting that coaches and researchers should look
      for a change of >5% to identify a meaningful change in both maximal back squat
      and power clean performance.

PMID- 25559913
TI  - Motivational Interviewing Tailored Interventions for Heart Failure (MITI-HF):
      study design and methods.
AB  - OBJECTIVE: Lack of engagement in self-care is common among patients needing to
      follow a complex treatment regimen, especially patients with heart failure who
      are affected by comorbidity, disability and side effects of poly-pharmacy. The
      purpose of Motivational Interviewing Tailored Interventions for Heart Failure
      (MITI-HF) is to test the feasibility and comparative efficacy of an MI
      intervention on self-care, acute heart failure physical symptoms and quality of
      life. METHODS: We are conducting a brief, nurse-led motivational interviewing
      randomized controlled trial to address behavioral and motivational issues related
      to heart failure self-care. Participants in the intervention group receive home
      and phone-based motivational interviewing sessions over 90-days and those in the
      control group receive care as usual. Participants in both groups receive patient
      education materials. The primary study outcome is change in self-care maintenance
      from baseline to 90-days. CONCLUSION: This article presents the study design,
      methods, plans for statistical analysis and descriptive characteristics of the
      study sample for MITI-HF. Study findings will contribute to the literature on the
      efficacy of motivational interviewing to promote heart failure self-care.
      PRACTICAL IMPLICATIONS: We anticipate that using an MI approach can help patients
      with heart failure focus on their internal motivation to change in a non
      confrontational, patient-centered and collaborative way. It also affirms their
      ability to practice competent self-care relevant to their personal health goals.

PMID- 25559914
TI  - Women In Steady Exercise Research (WISER) Sister: study design and methods.
AB  - PURPOSE: Women at elevated risk for breast cancer are motivated to reduce their
      risk. Current approaches rely primarily on hormonal intervention. A preventive
      exercise intervention might address the same hormonal issues, yet have fewer
      serious side effects and less negative impact on quality of life as compared to
      prophylactic mastectomy. WISER Sister was a randomized controlled trial which
      examined effects of two doses of exercise training on endogenous sex hormone
      exposure, hormonally active breast tissue, and other breast cancer risk factors.
      METHODS: Subjects for this single site trial were recruited from across the U.S.,
      in collaboration with organizations that serve women at elevated risk, via
      emails, flyers, and letters. Eligibility criteria included age >= 18,
      eumenorrheic, and at elevated risk for breast cancer (e.g. BRCA1 or BRCA2
      mutation and/or >= 18% lifetime risk according to prediction models). A 1:1:1
      randomization scheme was used to allocate participants into: control, low dose
      (150 min/week), or high dose (300 min/week) home based treadmill exercise.
      Participants provided first morning urine samples daily for two menstrual cycles
      at study beginning and end for calculation of endogenous hormone exposure. In
      addition, women completed breast dynamic contrast enhanced magnetic resonance
      imaging, a fasting blood draw, a treadmill exercise test, and surveys at baseline
      and follow-up. DISCUSSION: WISER Sister randomized 139 women, 122 of whom
      completed the study. The overall drop-out rate was 12%. Findings will be useful
      in understanding the potential for exercise to assist with reducing risk for
      breast cancer among women at elevated risk.

PMID- 25559915
TI  - Resistance Exercise in Already-Active Diabetic Individuals (READI): study
      rationale, design and methods for a randomized controlled trial of resistance and
      aerobic exercise in type 1 diabetes.
AB  - The Resistance Exercise in Already Active Diabetic Individuals (READI) trial
      aimed to examine whether adding a 6-month resistance training program would
      improve glycemic control (as reflected in reduced HbA1c) in individuals with type
      1 diabetes who were already engaged in aerobic exercise compared to aerobic
      training alone. After a 5-week run-in period including optimization of diabetes
      care and low-intensity exercise, 131 physically active adults with type 1
      diabetes were randomized to two groups for 22weeks: resistance training three
      times weekly, or waiting-list control. Both groups maintained the same volume,
      duration and intensity of aerobic exercise throughout the study as they did at
      baseline. HbA1c, body composition, frequency of hypoglycemia, lipids, blood
      pressure, apolipoproteins B and A-1 (ApoB and ApoA1), the ApoB-ApoA1 ratio,
      urinary albumin excretion, serum C-reactive protein, free fatty acids, total
      daily insulin dose, health-related quality of life, cardiorespiratory fitness and
      musculoskeletal fitness were recorded at baseline, 3 (for some variables), and 6
      months. To our knowledge, READI is the only trial to date assessing the
      incremental health-related impact of adding resistance training for individuals
      with type 1 diabetes who are already aerobically active. Few exercise trials have
      been completed in this population, and even fewer have assessed resistance
      exercise. With recent improvements in the quality of diabetes care, the READI
      study will provide conclusive evidence to support or refute a major clinically
      relevant effect of exercise type in the recommendations for physical activity in
      patients with type 1 diabetes.

PMID- 25559916
TI  - Design and rationale for NOURISH-T: a randomized control trial targeting parents
      of overweight children off cancer treatment.
AB  - Approximately 40% of off-treatment pediatric cancer survivors (PCS) are
      overweight or obese, which increases their risk for negative long-term physical
      health complications. Consistent with the Institute of Medicine's (IOM) emphasis
      on patients transitioning from treatment to cancer survivorship and increasing
      long-term healthy behaviors in these survivors, we plan to conduct a pilot RCT to
      address the increasing overweight/obesity rates among PCS by targeting their
      caregivers as agents for PCS behavior change. We plan to focus on parents'
      behaviors, attitudes and roles in promoting healthier eating and physical
      activity (PA) in PCS and adapt an evidence-informed, manualized parent
      intervention - NOURISH - found to be effective for parents of overweight and
      obese children and adolescents in reducing child and adolescent BMI. We plan to
      adapt NOURISH for caregivers of 5-12 year old PCS (6 months-4 years off active
      cancer treatment). Our pilot feasibility RCT - NOURISH-T (Nourishing Our
      Understanding of Role modeling to Improve Support for Healthy Transitions)
      evaluates: 1) the preliminary efficacy of NOURISH-T for PCS, compared with an
      Enhanced Usual Care (EUC) control condition, and 2) factors to consider to
      improve future adaptations of the intervention. The project will enroll
      caregivers of PCS at two pediatric oncology clinics into the 6-week intervention
      (or EUC) with assessments occurring pre- and post-6 weeks of intervention, and at
      a 4-month follow-up.

PMID- 25559917
TI  - MicroRNA-124 regulates neuronal differentiation of mesenchymal stem cells by
      targeting Sp1 mRNA.
AB  - MicroRNAs play an important role in neuronal development and function. miR-124 is
      the most abundantly expressed miRNA in the nervous system. Several different mRNA
      targets have been proposed for miR-124, but the precise function of endogenous
      miR-124 and its mRNA targets remain to be further elucidated. Specificity protein
      1 (Sp1) is a transcription factor that plays key roles in many cell processes
      including cell cycle. However, this transcription factor is nearly absent in
      differentiated neurons and a remarkable suppression of Sp1 expression was shown
      after neurogenesis. Since miR-124 is expressed abundantly in neurons and because
      Sp1 levels decrease during neurogenesis, it is possible that miR-124 could
      regulate the expression of Sp1 during neuronal development. Therefore, the aim of
      the present study was to evaluate the putative targeting of Sp1 by miR-124.
      Overexpression of miR-124 using a plasmid coding for pri-miR-124 in HEK293 cells
      decreased the expression of Sp1 mRNA. The results of dual-luciferase reporter
      assay demonstrated that miR-124 directly targeted the 3'-untranslated regions of
      Sp1 mRNA. To evaluate whether Sp1 expression was regulated by miR-124 during the
      process of neuronal differentiation, Adipose-derived mesenchymal stem cells (A
      MSCs) were differentiated into neuron-like cells. The results of qPCR analysis
      showed that with the gradual increase of miR-124 expression during neurogenesis,
      the expression of Sp1 mRNA decreased accordingly. In summary, this study
      demonstrated for the first time that miR-124 is able to suppress Sp1 expression,
      which in turn affected the neuronal differentiation of mesenchymal stem cells.

PMID- 25559919
TI  - Periodical shifts in the surgical correction of sagittal craniosynostosis.

PMID- 25559918
TI  - The enzymatic nature of an anonymous protein sequence cannot reliably be inferred
      from superfamily level structural information alone.
AB  - As the largest fraction of any proteome does not carry out enzymatic functions,
      and in order to leverage 3D structural data for the annotation of increasingly
      higher volumes of sequence data, we wanted to assess the strength of the link
      between coarse grained structural data (i.e., homologous superfamily level) and
      the enzymatic versus non-enzymatic nature of protein sequences. To probe this
      relationship, we took advantage of 41 phylogenetically diverse (encompassing 11
      distinct phyla) genomes recently sequenced within the GEBA initiative, for which
      we integrated structural information, as defined by CATH, with enzyme level
      information, as defined by Enzyme Commission (EC) numbers. This analysis revealed
      that only a very small fraction (about 1%) of domain sequences occurring in the
      analyzed genomes was found to be associated with homologous superfamilies
      strongly indicative of enzymatic function. Resorting to less stringent criteria
      to define enzyme versus non-enzyme biased structural classes or excluding highly
      prevalent folds from the analysis had only modest effect on this proportion.
      Thus, the low genomic coverage by structurally anchored protein domains strongly
      associated to catalytic activities indicates that, on its own, the power of
      coarse grained structural information to infer the general property of being an
      enzyme is rather limited. 

PMID- 25559920
TI  - Mechanical thrombectomy for pediatric stroke arising from an atrial myxoma: case
      report.
AB  - Children experiencing severe neurological deficit due to acute ischemic stroke
      may benefit from endovascular intervention. The authors describe the use of
      mechanical thrombectomy in the treatment of embolic occlusion secondary to an
      atrial myxoma in a pediatric patient. This case involved an 11-year-old boy with
      a history notable for Raynaud syndrome and a distal extremity rash who presented
      to the emergency department with dense hemiparesis secondary to thromboembolic
      occlusion of the M1 segment of the middle cerebral artery. Following mechanical
      thrombectomy, the patient's pediatric National Institutes of Health Stroke Scale
      score improved from a 16 to a 7. In the setting of acute pediatric stroke due to
      atrial myxoma emboli, mechanical thrombectomy may be a first-line therapy. 

PMID- 25559921
TI  - The incidence of raised intracranial pressure in nonsyndromic sagittal
      craniosynostosis following primary surgery.
AB  - OBJECT Raised intracranial pressure (ICP) is recognized to occur in patients with
      nonsyndromic isolated sagittal craniosynostosis (SC) prior to surgery. However,
      the incidence of raised ICP following primary surgery is rarely reported and
      there appears to be a widely held assumption that corrective surgery for SC
      prevents the later development of intracranial hypertension. This study reports
      the incidence of postoperative raised ICP in a large cohort of patients with SC
      treated by 1 of 2 surgical procedures in a single craniofacial unit. METHODS A
      retrospective review was performed of all patients with SC who underwent either a
      modified strip craniectomy (MSC) or calvarial remodeling (CR) procedure under the
      care of the Oxford Craniofacial Unit between 1995 and 2010 and who were followed
      up for more than 2 years. The influence of patient age at surgery, year of
      surgery, sex, procedure type, and the presence of raised ICP preoperatively were
      analyzed. RESULTS Two hundred seventeen children had primary surgery for SC and
      were followed up for a mean of 86 months. The overall rate of raised ICP
      following surgery was 6.9%, occurring at a mean of 51 months after the primary
      surgical procedure. Raised ICP was significantly more common in those patients
      treated by MSC (13 of 89 patients, 14.6%) than CR (2 of 128 patients, 1.6%).
      Also, raised ICP was more common in patients under 1 year of age, the majority of
      whom were treated by MCS. No other factor was found to have a significant effect.
      CONCLUSIONS Postoperative raised ICP was found in more than 1 in 20 children
      treated for nonsyndromic SC in this series. It was significantly influenced by
      the primary surgical procedure and age at primary surgery. Careful long-term
      follow-up is essential if children who develop raised ICP following surgery are
      not to be overlooked. 

PMID- 25559922
TI  - Disparities in clinical and economic outcomes in children and adolescents
      following surgery for tethered cord syndrome in the United States.
AB  - OBJECT: Tethered cord syndrome (TCS) is a common spinal abnormality. In this
      study, the authors analyzed demographics, complications, and outcomes in children
      and adolescents who underwent surgery for TCS. METHODS: Using the national Kids'
      Inpatient Database (KID), the authors retrospectively identified patients with a
      primary diagnosis of TCS who were treated with spinal laminectomy and discharged
      in 2000, 2003, 2006, and 2009. Descriptive analysis was provided for patient- and
      hospital-level characteristics. Mortality, complications, non-routine discharges,
      in-hospital length of stay (LOS), and total charges were documented for the
      entire cohort and age-specific cohorts (0-5, 6-10, 11-15, and 16-20 years).
      Comparisons by complications and age groups were conducted. RESULTS: A total of
      7397 children and adolescents met the criteria in the 4 studied years. The mean
      age was 5.7 years; 55.3% of patients were younger than 5 years, 21.5% were 6-10
      years, and 16.2% were 11-15 years. Most surgeries were performed in patients who
      were female (55.0%) and white (64.4%) and were performed at large (49.8%),
      teaching (94.2%), and urban (99.1%) children's (89.3%) hospitals. The trend
      showed an increase in prevalence from 2000 (19.9%) to 2009 (29.6%). Common
      comorbidities included anomalies in spinal curvature (16.7%), urinary or bladder
      dysfunction (14.3%), and spinal stenosis/spondylosis (1.4%). Non-routine
      discharges (3.3%) were significantly higher with advancing age, increasing from
      2.2% in those younger than 5 years to 9.0% in those older than 15 years (p <
      0.0001). There was a similar increasing trend for complications (6.8% to 13.9%,
      respectively, p < 0.0001) and average LOS (3.5 to 5.1 days, respectively, p <
      0.0001). Hospital charges increased with age from an average of $28,521 in those
      younger than 5 years to $36,855 in those older than 15 years (p < 0.0001).
      CONCLUSIONS: There was a steady trend of increasing operative treatment for TCS
      over the more recent years. The nationwide analysis was also indicative of an
      existing disparity, based on age, in complications, outcomes, and charges
      following TCS surgical correction. Older children tended to have more
      complications, longer LOS, more non-routine discharges, and higher hospital
      costs. The results are highly supportive of surgery at a younger age for this
      condition. Future research should investigate this correlation, especially
      considering the efforts to control and reduce health care costs.

PMID- 25559923
TI  - Surgical bailout of giant supraclinoid ICA aneurysm following treatment with
      Pipeline Embolization Device.

PMID- 25559924
TI  - Cranial base pathology in pediatric osteogenesis imperfecta patients treated with
      bisphosphonates.
AB  - OBJECT: Cranial base pathology is a serious complication of osteogenesis
      imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to
      improve bone strength, could also prevent the development of craniocervical
      junction pathology (basilar impression, basilar invagination, or platybasia) in
      children with OI. METHODS: In this single-center retrospective study the authors
      analyzed the skull base morphology from lateral skull radiographs and midsagittal
      MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39
      bisphosphonate-treated OI patients. The results were compared with age-matched
      normative values and with findings in 70 OI patients who were not treated with
      bisphosphonates. In addition to cross-sectional data, longitudinal data were
      available from 22 patients with an average follow-up period of 7.6 years. The
      patients, who had OI types I, III, IV, VI, and VII, had been treated with
      zoledronic acid, pamidronate, or risedronate for 3.2 years on average. RESULTS:
      Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial
      base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic
      regression analysis suggested a higher risk of basilar impression or invagination
      in patients with severe OI (OR 22.04) and/or older age at initiation of
      bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with
      longer duration of treatment (OR 0.28). No significant associations between age,
      height, or cumulative bisphosphonate dose and the risk for cranial base anomaly
      were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed
      development of cranial base pathology in patients treated with bisphosphonates
      but the differences from the untreated group were not statistically significant.
      CONCLUSIONS: These findings indicate that cranial base pathology may develop
      despite bisphosphonate treatment. Early initiation of bisphosphonate treatment
      may delay development of craniocervical junction pathology. Careful followup of
      cranial base morphology is warranted, particularly in patients with severe OI.

PMID- 25559925
TI  - Predicting People's Intention to Donate Their Body to Medical Science and
      Research.
AB  - Predictors of people's intention to register with a body bequest program for
      donating their deceased body to medical science and research were examined using
      standard theory of planned behavior (TPB) predictors (attitude, subjective norm,
      perceived behavioral control) and adding moral norm, altruism, and knowledge.
      Australian students (N = 221) at a university with a recently established body
      bequest program completed measures of the TPB's underlying beliefs (behavioral,
      normative, and control beliefs) and standard and extended TPB predictors, with a
      sub-sample reporting their registration-related behavior 2 months later. The
      standard TPB accounted for 43.6%, and the extended predictors an additional 15.1%
      of variance in intention. The significant predictors were attitude, subjective
      norm, and moral norm, partially supporting an extended TPB in understanding
      people's body donation intentions. Further, important underlying beliefs can
      inform strategies to target prospective donors. 

PMID- 25559926
TI  - Increased diagnostic activity in general practice during the year preceding
      colorectal cancer diagnosis.
AB  - Accurate diagnostic activity in general practice before colorectal cancer (CRC)
      diagnosis is crucial for an early detection of CRC. This study aimed to
      investigate the rates of daytime consultations, hemoglobin (Hb) measurements and
      medicine prescriptions for hemorrhoids in general practice in the year preceding
      CRC diagnosis. Using Danish registries, we conducted a population-based matched
      cohort study including CRC patients aged 40-80 years (n = 19,209) and matched
      references (n = 192,090). We calculated odds ratios (ORs) using a conditional
      logistical regression model and incidence rate ratios (IRRs) using a negative
      binomial regression model. The CRC patients had significantly more consultations
      from 9 months before diagnosis and significantly increased rates of Hb
      measurements from up to 17 months before diagnosis compared with references.
      Furthermore, up to 18 months before diagnosis, CRC patients had significantly
      higher rates of prescriptions for hemorrhoids; and 2 months before diagnosis, the
      IRR was 12.24 (95% confidence interval (CI): 10.29-14.55) for men. The positive
      predictive value (PPV) of CRC for having a first-time prescription for
      hemorrhoids was highest among men aged 70-80 years [PPV = 3.2% (95% CI: 2.8
      3.7)]. High prescription rates were predominantly seen among rectal cancer
      patients, whereas colon cancer patients had higher rates of consultations and Hb
      measurements. This study revealed a significant increase in healthcare seeking
      and diagnostic activity in general practice in the year prior to CRC diagnosis,
      which indicates the presence of a "diagnostic time window" and a potential for
      earlier diagnosis of CRC based on clinical signs and symptoms. 

PMID- 25559927
TI  - Intake patterns and dietary associations of soya protein consumption in adults
      and children in the Canadian Community Health Survey, Cycle 2.2.
AB  - Soya foods are one of the recommended alternatives to meat in many dietary
      guidelines. While this is expected to increase the intake of some nutrients,
      potential concerns regarding others have been raised. The purpose of the present
      study was to examine the prevalence and the association of soya food consumption
      with nutrient intakes and dietary patterns of Canadians (age >= 2 years). Cross
      sectional data from the 2004 Canadian Community Health Survey (Cycle 2.2; n
      33,218) were used to classify soya consumers and non-consumers. Soya consumers
      were further divided into two groups based on their soya protein intake. Sample
      weights were applied and logistic regression analysis was used to explore the
      association between nutrient intakes and soya consumption, with cultural
      background, sex, age and economic status being included as covariates. On any
      given day, 3.3% (n 1085) of Canadians consume soya foods, with females, Asian
      Canadians and adults with post-secondary education being more likely to be soya
      consumers. As a whole, adolescent and adult respondents who had consumed at least
      one soya food during their 24 h dietary recall had higher energy intakes, as well
      as increased intakes of nutrients such as protein, fibre, vitamin C, vitamin B6,
      naturally occurring folate, thiamin, Ca, P, Mg, PUFA, Fe and K and lowered
      intakes of saturated fat. These data indicate that soya food consumption is
      associated with improved diet quality of Canadians. However, future research is
      necessary to investigate the association between increased energy intake and soya
      consumption.

PMID- 25559928
TI  - Editorial commentary: international perspectives on food and nutrition.

PMID- 25559930
TI  - Enhanced QSAR models for drug-triggered inhibition of the main cardiac ion
      currents.
AB  - The currently changing cardiac safety testing paradigm suggests, among other
      things, a shift towards using in silico models of cellular electrophysiology and
      assessment of a concomitant block of multiple ion channels. In this study, a set
      of four enhanced QSAR models have been developed: for the rapid delayed
      rectifying potassium current (IKr), slow delayed rectifying potassium current
      (IKs), peak sodium current (INa) and late calcium current (ICaL), predicting ion
      currents changes for the specific in vitro experiment from the 2D structure of
      the compounds. The models are a combination of both in vitro study parameters and
      physico-chemical descriptors, which is a novel approach in drug-ion channels
      interactions modeling. Their predictive power assessed in the enhanced, more
      demanding than standard procedure, 10-fold cross validation was reasonably high.
      Rough comparison with published pure in silico hERG interaction models shows that
      the quality of the model predictions does not differ from other models available
      in the public domain, however, it takes its advantage in accounting for inter
      experimental settings variability. Developed models are implemented in the
      Cardiac Safety Simulator, a commercially available platform enabling the in vitro
      in vivo extrapolation of the drugs proarrhythmic effect and ECG simulation. A
      more comprehensive assessment of the effects of the compounds on ion channels
      allows for making more informed decisions regarding the risk - and thus avoidance
      - of exclusion of potentially safe and effective drugs.

PMID- 25559929
TI  - Consequences of periodic alpha-to-beta(3) residue replacement for immunological
      recognition of peptide epitopes.
AB  - Oligomers that contain both alpha- and beta-amino acid residues, or "alpha/beta
      peptides", have emerged as promising mimics of signal-bearing polypeptides that
      can inhibit or augment natural protein-protein interactions. alpha/beta-Peptides
      that contain a sufficient proportion of beta residues evenly distributed along
      the sequence can be highly resistant to enzymatic degradation, which is favorable
      with regard to in vivo applications. Little is known, however, about recognition
      of alpha/beta-peptides by the immune system. Prior studies have focused almost
      entirely on examples that contain a single beta residue; such alpha/beta-peptides
      frequently retain the immunological profile of the analogous alpha-peptide. We
      have conducted alpha-peptide vs alpha/beta-peptide comparisons involving higher
      beta residue content, focusing on molecules with alphaalphaalphabeta and
      alphaalphabetaalphaalphaalphabeta backbone repeat patterns. Among analogues of an
      18-mer derived from the Bim BH3 domain and an 8-mer derived from secreted
      phospholipase-2 (sPLA2), we find that recognition by antibodies raised against
      the prototype alpha-peptide is suppressed by periodic alpha -> beta replacements.
      Complementary studies reveal that antibodies raised against Bim BH3- or sPLA2
      derived alpha/beta-peptides fail to recognize prototype alpha-peptides displaying
      identical side chain repertoires. Because polypeptides containing d-alpha-amino
      acid residues are of growing interest for biomedical applications, we included
      the enantiomer of the sPLA2-derived alpha-peptide in these studies; this d
      peptide is fully competent as a hapten, but the resulting antibodies do not cross
      react with the enantiomeric peptide. Among analogues of the 9-mer CD8(+) T-cell
      viral epitope GP33, we observe that periodic alpha -> beta replacements suppress
      participation in the MHC I + peptide + T-cell receptor ternary complexes that
      activate cytotoxic T-lymphocytes, due in part to disruption of MHC binding.

PMID- 25559931
TI  - Altered iPSC-derived neurons' sodium channel properties in subjects with Monge's
      disease.
AB  - Monge's disease, also known as chronic mountain sickness (CMS), is a disease that
      potentially threatens more than 140 million highlanders during extended time
      living at high altitudes (over 2500m). The prevalence of CMS in Andeans is about
      15-20%, suggesting that the majority of highlanders (non-CMS) are rather healthy
      at high altitudes; however, CMS subjects experience severe hypoxemia,
      erythrocytosis and many neurologic manifestations including migraine, headache,
      mental fatigue, confusion, and memory loss. The underlying mechanisms of CMS
      neuropathology are not well understood and no ideal treatment is available to
      prevent or cure CMS, except for phlebotomy. In the current study, we reprogrammed
      fibroblast cells from both CMS and non-CMS subjects' skin biopsies into the
      induced pluripotent stem cells (iPSCs), then differentiated into neurons and
      compared their neuronal properties. We discovered that CMS neurons were much less
      excitable (higher rheobase) than non-CMS neurons. This decreased excitability was
      not caused by differences in passive neuronal properties, but instead by a
      significantly lowered Na(+) channel current density and by a shift of the voltage
      conductance curve in the depolarization direction. Our findings provide, for the
      first time, evidence of a neuronal abnormality in CMS subjects as compared to non
      CMS subjects, hoping that such studies can pave the way to a better understanding
      of the neuropathology in CMS.

PMID- 25559932
TI  - Diagnostic performance of heavily T2-weighted techniques in obstructive
      hydrocephalus: comparison study of two different 3D heavily T2-weighted and
      conventional T2-weighted sequences.
AB  - PURPOSE: To evaluate efficacy of three-dimensional (3D) heavily T2-weighted (W)
      MRI sequences in assessment of cerebrospinal fluid (CSF) pathways and to compare
      two different types of 3D heavily T2W MRI sequences (CISS and SPACE) with two
      dimensional (2D) T2W turbo spin echo (TSE) sequences for hydrocephalus with
      intraventricular obstruction. MATERIALS AND METHODS: Sixty-two patients who were
      diagnosed with intraventricular obstructive hydrocephalus, according to clinical
      and radiological findings, were included in this retrospective study. 2D-TSE-T2,
      3D-CISS, and 3D-SPACE, which are part of the protocol, were analyzed
      quantitatively by measuring ventricle-to-parenchyma contrast-to-noise ratio
      (CNR), and qualitatively by evaluating the capabilities of visualization of the
      obstructive pathology, overall image quality, severity of artifacts, and
      delineation of the CSF pathways. One-way ANOVA and Friedman's test were used for
      statistical analysis. RESULTS: CNR between CSF and brain parenchyma was
      significantly higher using 3D-SPACE sequences compared with 3D-CISS and 2D-TSE-T2
      sequences. The qualitative findings showed that 3D heavily T2W sequences were
      superior to 2D-TSE-T2 sequences. 3D-SPACE sequences showed fewer artifacts than
      3D-CISS or 2D-TSE-T2 sequences. CONCLUSION: 3D heavily T2W sequences are
      necessary tools for assessment of CSF pathways in patients with intraventricular
      obstructive hydrocephalus. 3D-SPACE sequences allowed heavy T2W, which is
      necessary for CSF flow imaging and provided significantly fewer image artifacts
      and improved CNR in comparison with 3D-CISS sequences.

PMID- 25559933
TI  - Diffusion-weighted imaging-detected ischemic lesions associated with flow
      diverting stents in intracranial aneurysms: safety, potential mechanisms,
      clinical outcome, and concerns.
AB  - OBJECT: It was initially considered safe for flow-diverting stents to cover the
      ostia of branching vessels during endovascular procedures for the treatment of
      intracranial aneurysms. As more recent evidence suggests, however, their use is
      not always free of ischemic concerns in terms of covered arterial ostia. The
      authors sought to determine the frequency of silent and clinically evident
      diffusion-weighted imaging (DWI)-detected abnormalities related to stent
      placement as a means of elucidating potential clinical risks. METHODS: This is a
      prospective single-center study on a series of patients with intracranial
      aneurysms that were treated with flow-diverting stents. All patients
      systematically underwent an MRI protocol that included DWI before treatment,
      between 24 and 48 hours postprocedure, and 3 months postembolization.
      Effectiveness of anticoagulation treatment was assessed for all patients. Lesions
      seen on DWI were correlated to the parent artery and the side-branch territories
      and were statistically analyzed in relation to their time of occurrence and
      clinical presentation. The authors compared the DWI findings in these patients to
      findings obtained in patients treated with a stent-assisted coiling technique
      during the same time period. RESULTS: Over the course of 18 consecutive months,
      38 consecutive patients (7 males and 31 females) with 49 intracranial aneurysms
      were treated using flow-diverting stents. Overall, 81.6% of the DWI spots found
      remained clinically silent during the follow-up period. Five ischemic clinical
      complications (13.2%) occurred in the postprocedural period. No statistically
      significant correlation could be established between DWI spots or aneurysm
      location and clinical complications or follow-up modified Rankin Scale score at 3
      months. The complication rate was 7.8% (n = 3) at the 3-month follow-up, and
      mortality was 0%. Compared with stent-assisted coiling, use of flow-diverting
      stents showed a statistically significant correlation with silent DWI findings
      postintervention. CONCLUSIONS: Lesions seen on DWI resulting from the procedure
      are far more common than anticipated, but the technique remains safe and
      effective, providing an interesting alternative for "difficult" aneurysms,
      regardless of location. Late-occurring DWI-detected lesions distal to side
      arterial branches imply a local pressure gradient drop, related to flow
      competition by collateral networks. Further research is needed to assess the
      extent and significance of these events.

PMID- 25559935
TI  - Activity classification in persons with stroke based on frequency features.
AB  - Recent advances in the use of inertial measurement units (IMUs) for motion
      analysis suggest the possibility of using this technology for the monitoring of
      daily activities of individuals during rehabilitation post-stroke. Previous
      studies have utilized features extracted from accelerometer and gyroscope signals
      to develop classification models capable of identifying activities performed
      within large datasets. In this study, nine k-nearest neighbor cross-validated
      classifiers were developed using frequency-features derived from shank-mounted
      IMUs on the less-affected and affected limbs of subjects with stroke. These
      classifiers were evaluated for two separate datasets of post-stroke gait; the
      first a classification of three separate gait activities (overground walking,
      stair ascent, and stair descent), and the second a classification of five gait
      activities, overground walking, stair ascent, and descent with a distinction
      between stepping pattern used while negotiating stairs (step-over-step (SOS) and
      step-by-step (SBS)). The comparison showed the highest classification accuracy,
      100% for the three-activities and 94% for the five-activities, was obtained using
      a classifier composed of features derived from accelerometer and gyroscope
      measurements from both IMUs on less-affected and affected limbs. 

PMID- 25559934
TI  - Recommendations service for chronic disease patient in multimodel sensors home
      environment.
AB  - With advanced technologies in hand, there exist potential applications and
      services built around monitoring activities of daily living (ADL) of elderly
      people at nursing homes. Most of the elderly people in these facilities are
      suffering from different chronic diseases such as dementia. Existing technologies
      are mainly focusing on non-medication interventions and monitoring of ADL for
      addressing loss of autonomy or well-being. Monitoring and managing ADL related to
      cognitive behaviors for non-medication intervention are very effective in
      improving dementia patients' conditions. However, cognitive functions of patients
      can be improved if appropriate recommendations of medications are delivered at a
      particular time. Previously we developed the Secured Wireless Sensor Network
      Integrated Cloud Computing for Ubiquitous-Life Care (SC(3)). SC(3) services were
      limited to monitoring ADL of elderly people with Alzheimer's disease and
      providing non-medication recommendations to the patient. In this article, we
      propose a system called the Smart Clinical Decision Support System (CDSS) as an
      integral part of the SC(3) platform. Using the Smart CDSS, patients are provided
      with access to medication recommendations of expert physicians. Physicians are
      provided with an interface to create clinical knowledge for medication
      recommendations and to observe the patient's condition. The clinical knowledge
      created by physicians as the knowledge base of the Smart CDSS produces
      recommendations to the caregiver for medications based on each patient's
      symptoms. 

PMID- 25559936
TI  - Induction of Hepatic and Endothelial Differentiation by Perfusion in a Three
      Dimensional Cell Culture Model of Human Fetal Liver.
AB  - The development of functional engineered tissue constructs depends on high cell
      densities and appropriate vascularization. In this study we implemented a four
      compartment three-dimensional perfusion bioreactor culture model for studying the
      effects of medium perfusion on endothelial, hepatic, and hematopoietic cell
      populations of primary human fetal liver in an in vivo-like environment. Human
      fetal liver cells were cultured in bioreactors configured to provide either
      perfusion or diffusion conditions. Metabolic activities of the cultures were
      monitored daily by measuring glucose consumption and lactate production. Cell
      viability during culture was analyzed by lactate dehydrogenase activity. Hepatic
      functionality was determined by the release of albumin and alpha-fetoprotein
      (AFP) in culture medium samples. After 4 days of culture, cells were analyzed for
      the expression of a variety of endothelial, hepatic, and hematopoietic genes, as
      well as the surface marker expression of CD31 and CD34 in flow cytometry. We
      found that medium perfusion increased the gene expression of endothelial markers
      such as CD31, von Willebrand factor (vWF), CD140b, CD309, and CD144 while
      decreasing the gene expression of the erythrocyte-surface marker CD235a. Hepatic
      differentiation was promoted under perfusion conditions as demonstrated by lower
      AFP and higher albumin secretion compared with cultures not exposed to medium
      perfusion. Additionally, cultures exposed to medium perfusion gave higher rates
      of glucose consumption and lactate production, indicating increased metabolic
      activity. In conclusion, high-density bioreactors configured to provide constant
      medium perfusion significantly induced hepatic and endothelial cell
      differentiation and provided improved conditions for the culture of human fetal
      liver cells compared with cultures without perfusion. 

PMID- 25559937
TI  - Internal carotid artery dissection after a roller coaster ride in a 4-year-old:
      case report and review of the literature.
AB  - BACKGROUND: Strokes associated with roller-coaster rides are unusual. PATIENT: A
      previously healthy 4-year-old boy developed acute onset of left-sided weakness
      when flying home from a trip to an amusement park. He had frequented two roller
      coaster rides the day prior. Upon evaluation, he was found to have an acute right
      middle cerebral artery territory infarction. RESULTS: Cerebral angiography showed
      dissection of the right cervical internal carotid artery and right middle
      cerebral artery occlusion involving the M1 segment. He was treated with aspirin.
      Evaluation for underlying connective tissue diseases was unremarkable.
      CONCLUSION: We speculate that repetitive forces of acceleration and deceleration
      may have led to a cervical internal carotid artery intimal tear, followed by
      thromboembolism. It remains uncertain what the threshold of susceptibility to
      repetitive rotational changes and tolerability to G forces in an otherwise
      healthy child truly is.

PMID- 25559938
TI  - Hemiparesis and epilepsy are associated with worse reported health status
      following unilateral stroke in children.
AB  - BACKGROUND: Perinatal and childhood stroke result in neurological impairment in
      the majority of survivors, but less is known about patient and parent perception
      of function following stroke in children. Our aim was to characterize parent
      proxy and child-reported health status in children following unilateral arterial
      ischemic stroke or intraparenchymal hemorrhage. METHODS: Fifty-nine children 2-18
      years (30 girls, 29 boys) with unilateral arterial ischemic stroke or spontaneous
      intraparenchymal hemorrhage at least 6 months before evaluation were enrolled
      from a single center. The PedsQL version 4.0 Generic Short Form and PedsQL
      version 3.0 Cerebral Palsy Module were administered to childhood stroke subjects
      and parents. Generic PedsQL Inventory scores were compared between children with
      stroke and published data from healthy children. Reported health status scores
      for children with varying degrees of hemiparesis were compared. RESULTS: Children
      with stroke had lower reported health status scores on the Generic PedsQL
      Inventory than healthy children. Children with moderate-severe hemiparesis had
      worse scores than children without hemiparesis on several measures of the
      Cerebral Palsy Module as reported by both parents and children. The parents of
      children with epilepsy reported worse scores on several measures compared with
      children without epilepsy, and the parent scores were lower on several measures
      for children with lower intelligence quotients. Agreement between parent and
      child scores was better on the Cerebral Palsy Module than on the Generic
      Inventory. CONCLUSIONS: Children with stroke have worse reported health status
      than healthy controls. Degree of hemiparesis, epilepsy, and lower intelligence
      quotient affect reported health status on some measures. Agreement between parent
      proxy and child scores ranges from slight to good which suggests that both
      provide useful information.

PMID- 25559939
TI  - Reference values for three channels of amplitude-integrated EEG using the Brainz
      BRM3 cerebral function monitor in normal term neonates: a pilot study.
AB  - BACKGROUND: Amplitude-integrated electroencephalography (EEG) is a form of
      continuous EEG using a select number of electrodes (2-4), which can be used for
      bedside monitoring of brain functions in critically ill neonates. There is a
      paucity of normative amplitude-integrated EEG data for term healthy neonates
      especially for unilateral channels that are available for newer cerebral function
      monitors. OBJECTIVE: To define absolute amplitudes for all three available
      channels and also to determine if route of delivery or presence of a caput
      succedaneum would affect amplitude-integrated EEG amplitude voltages. METHODS:
      This is a prospective observational study of 80 healthy term neonates
      (gestational age >= 38 weeks) who had three-channel amplitude-integrated EEG
      recorded for 90 minutes within 12 hours of birth using the Brainz BRM3 cerebral
      function monitor. RESULTS: Median maximum and median minimum voltages obtained
      were 16.96 MUV and 8.13 MUV for the cross-cerebral (CC), 14.42 MUV and 7.13 MUV
      for the right unilateral, and 13.16 MUV and 6.51 MUV for the left unilateral aEEG
      channels, respectively. There were no statistically significant difference
      amplitude voltages for any channel based on route of delivery. The presence of a
      caput succedaneum was associated with a decrease in the median and mean of the
      maximum and minimum amplitude voltages for CC channel. Median maximum and median
      minimum voltages for the CC channel among the caput and normal scalp examination
      groups were 14.62 MUV vs 17.27 MUV (P = 0.022) and 7.21 MUV vs 8.24 MUV (P =
      0.004), respectively. Similarly, mean maximum and mean minimum voltages for the
      CC channel were 15.42 MUV vs 17.59 MUV (P = 0.038) and 7.27 MUV vs 8.25 MUV (P =
      0.005) in the caput and normal scalp examination groups, respectively.

PMID- 25559940
TI  - The Communication Function Classification System: cultural adaptation, validity,
      and reliability of the Farsi version for patients with cerebral palsy.
AB  - BACKGROUND: This study developed a Farsi language Communication Function
      Classification System and then tested its reliability and validity. METHODS:
      Communication Function Classification System is designed to classify the
      communication functions of individuals with cerebral palsy. Up until now, there
      has been no instrument for assessment of this communication function in Iran. The
      English Communication Function Classification System was translated into Farsi
      and cross-culturally modified by a panel of experts. Professionals and parents
      then assessed the content validity of the modified version. A backtranslation of
      the Farsi version was confirmed by the developer of the English Communication
      Function Classification System. Face validity was assessed by therapists and
      parents of 10 patients. The Farsi Communication Function Classification System
      was administered to 152 individuals with cerebral palsy (age, 2 to 18 years;
      median age, 10 years; mean age, 9.9 years; standard deviation, 4.3 years). Inter
      rater reliability was analyzed between parents, occupational therapists, and
      speech and language pathologists. The test-retest reliability was assessed for 75
      patients with a 14 day interval between tests. RESULTS: The inter-rater
      reliability of the Communication Function Classification System was 0.81 between
      speech and language pathologists and occupational therapists, 0.74 between
      parents and occupational therapists, and 0.88 between parents and speech and
      language pathologists. The test-retest reliability was 0.96 for occupational
      therapists, 0.98 for speech and language pathologists, and 0.94 for parents.
      CONCLUSIONS: The findings suggest that the Farsi version of Communication
      Function Classification System is a reliable and valid measure that can be used
      in clinical settings to assess communication function in patients with cerebral
      palsy.

PMID- 25559941
TI  - The non-foliar hypoxic photosynthetic syndrome: evidence for enhanced pools and
      functionality of xanthophyll cycle components and active cyclic electron flow in
      fruit chlorenchyma.
AB  - MAIN CONCLUSION: Green fruits display a high engagement in CEF and enhanced VAZ
      cycle activity as a response to the demands imposed by their internal aerial
      conditions, particularly low O 2 , due to gas exchange limitations. In the
      present study, we used HPLC analysis, post-illumination changes in fluorescence
      yield under varying O2 and CO2 partial pressures and absorbance changes at 820 nm
      induced by far-red light to assess the carotenoid composition, the functionality
      of the xanthophyll cycle (VAZ) and the possibility of an active cyclic e (-) flow
      (CEF) in the fully exposed green fruits from Nerium oleander and Rosa sp. Equally
      exposed, mature leaves served as controls. Compared to leaves, fruits display
      less total chlorophylls and carotenoids but higher Car/Chl ratio, mainly shaped
      by the increased pools of the VAZ cycle components, in both species. The enhanced
      VAZ pool size in fruits is combined with a higher mid-day de-epoxidation state
      (DEPS). Moreover, fruits exhibit considerably lower levels of oxidizable P700, a
      faster re-reduction of PSI and significantly higher relative magnitude of CEF,
      irrespective of the O2/CO2 levels applied. We conclude that the higher VAZ
      investment may serve the enhanced heat dissipation needs in fruits, in the
      presence of a suppressed linear e (-) flow. In addition, the elevated potential
      of CEF may replenish the ATP lost due to hypoxia and concurrently facilitate the
      development of adequate non-photochemical quenching (NPQ), through its
      contribution to DeltapH increase. Since other non-foliar green organs exhibit a
      similar photosynthetic pattern, we argue that this may reflect a common strategy
      for green tissues under similar micro-environmental conditions, particularly
      hypoxia.

PMID- 25559942
TI  - Crystal structure of a plant albumin from Cicer arietinum (chickpea) possessing
      hemopexin fold and hemagglutination activity.
AB  - MAIN CONCLUSION: Crystal structure of a reported PA2 albumin from Cicer arietinum
      shows that it belongs to hemopexin fold family, has four beta-propeller motifs
      and possesses hemagglutination activity, making it different from known legume
      lectins. A plant albumin (PA2) from Cicer arietinum, presumably a lectin (CAL)
      owing to its hemagglutination activity which is inhibited by complex sugars as
      well as glycoproteins such as fetuin, desialylated fetuin and fibrinogen. The
      three-dimensional structure of this homodimeric protein has been determined using
      X-ray crystallography at 2.2 A in two crystal forms: orthorhombic (P21212) and
      trigonal (P3). The structure determined using molecular replacement method and
      refined in orthorhombic crystal form reached R-factors R free 22.6 % and R work
      18.2 % and in trigonal form had 22.3 and 17.9 % in the resolution range of 20.0
      2.2 and 35.3-2.2 A, respectively. Interestingly, unlike the known legume lectin
      fold, the structure of this homodimeric hemagglutinin belonged to hemopexin fold
      that consisted of four-bladed beta-propeller architecture. Each subunit has a
      central cavity forming a channel, inside of which is lined with hydrophobic
      residues. The channel also bears binding sites for ligands such as calcium,
      sodium and chloride ions, iodine atom in the case of iodine derivative and water
      molecules. However, none of these ligands seem important for the sugar
      recognition. No monosaccharide sugar specificity could be detected using
      hemagglutination inhibition. Chemical modification studies identified a potential
      sugar-binding site per subunit molecule. Comparison of C-alpha atom positions in
      subunit structures showed that the deviations between the two crystal forms were
      more with respect to blades I and IV. Differences also existed between subunits
      in two forms in terms of type and site of ligand binding.

PMID- 25559943
TI  - An integrative approach for measuring semantic similarities using gene ontology.
AB  - BACKGROUND: Gene Ontology (GO) provides rich information and a convenient way to
      study gene functional similarity, which has been successfully used in various
      applications. However, the existing GO based similarity measurements have limited
      functions for only a subset of GO information is considered in each measure. An
      appropriate integration of the existing measures to take into account more
      information in GO is demanding. RESULTS: We propose a novel integrative measure
      called InteGO2 to automatically select appropriate seed measures and then to
      integrate them using a metaheuristic search method. The experiment results show
      that InteGO2 significantly improves the performance of gene similarity in human,
      Arabidopsis and yeast on both molecular function and biological process GO
      categories. CONCLUSIONS: InteGO2 computes gene-to-gene similarities more
      accurately than tested existing measures and has high robustness. The
      supplementary document and software are available at http://mlg.hit.edu.cn:8082/.

PMID- 25559944
TI  - Regional fat distribution in adolescent and adult females with anorexia nervosa:
      A longitudinal study.
AB  - BACKGROUND & AIMS: No study has yet compared body fat distribution before and
      after weight restoration in adolescent and adult patients with anorexia nervosa
      (AN) treated according to the same protocol. The study was set up to measure body
      fat distribution before and after short-term weight restoration in adolescent and
      adult patients with AN treated according to the same protocol in a specialist
      inpatient unit. METHODS: We recruited 33 consecutive adolescent female patients
      with AN, and 33 controls matched by age and post-treatment BMI centile, as well
      as 33 adult female patients with AN, and 33 controls matched by age and post
      treatment BMI. Dual-energy X-ray absorptiometry (DXA) was used to assess body
      composition before and after short-term weight restoration (BMI >= 18.5 kg/m2).
      RESULTS: Compared with controls, both adolescents and adults with AN showed that
      a greater amount of fat was lost from the extremities than the trunk before
      weight restoration, and that there was a central adiposity phenotype after short
      term weight restoration. There were no significant differences in body fat
      distribution between adolescents and adults with AN before or after short-term
      weight restoration. CONCLUSIONS: Adolescent and adult females with AN have
      similar body fat distribution both before and after short-term weight
      restoration, and show a central adiposity phenotype after short-term weight
      restoration. The clinical implications of this finding are as yet unknown.
      Clinical Trials Registry- Regional Fat Distribution in Adolescent Girls and
      Adults with Anorexia Nervosa (ISRCTN73572502).

PMID- 25559945
TI  - Association between magnesium status, oxidative stress and inflammation in
      preeclampsia: A case-control study.
AB  - BACKGROUND & AIMS: Preeclampsia is responsible for more than one-third of all
      maternal deaths in Brazil. The objectives of the present study were to evaluate
      magnesium status and its association with oxidative stress and inflammation in
      preeclamptic women, and to identify the predictor variables of the disorder.
      METHODS: The study population consisted of 36 women divided into preeclamptic (n
      = 18) and control groups (n = 18). The preeclamptic group included women (>=20
      weeks of pregnancy) with arterial pressure >= 140/90 mmHg and proteinuria >0.3
      g/24 h, while the control group comprised pregnant women with no
      clinical/obstetric complications. Magnesium intake was assessed via a food
      frequency questionnaire validated for pregnant women in Brazil. Plasma,
      erythrocyte and urinary magnesium levels were determined by flame atomic
      absorption spectroscopy, while oxidative stress and inflammatory markers were
      assessed using standard protocols. Logistic regression analysis was used to
      identify the predictors of preeclampsia. RESULTS: Preeclamptic and control groups
      were similar with respect to magnesium intake and urinary excretion, while plasma
      and erythrocyte magnesium concentrations were higher in the former group. Plasma
      magnesium was positively correlated with catalase and glutathione peroxidase
      activities and with concentrations of interleukin-6 and tumor necrosis factor
      alpha. Regression analysis showed that plasma magnesium and urinary 8-isoprostane
      were associated with preeclampsia. CONCLUSION: Magnesium status appears to result
      from homeostatic imbalance and physiological alterations typical of preeclampsia.
      Increased plasma magnesium and decreased urinary 8-isoprostane were considered
      predictors of preeclampsia.

PMID- 25559946
TI  - The diagnostic value of survivin in malignant pleural effusion: a meta-analysis.
AB  - BACKGROUND: Survivin in pleural effusion is a promising marker for the diagnosis
      of malignant pleural effusion. METHODS: Based on the principles and methods of
      Cochrane systematic reviews, PubMed, EMBASE, Web of Knowledge (ISI), the Cochrane
      Library, and China National Knowledge Infrastructure (CNKI) databases were
      searched to identify studies that assessed the diagnostic value of survivin in
      pleural effusion for malignant pleural effusion. Stata 12 and Meta-disc 1.4
      software were used to test the heterogeneity and to perform the meta-analysis.
      RESULTS: Our search returned 167 articles, of which ten fulfilled the inclusion
      criteria. These studies included a total of 614 patients with malignant pleural
      effusion and 430 patients with benign pleural effusion as controls. The summary
      assessments revealed that the pooled sensitivity was 0.86 (95% CI: 0.82-0.88) and
      the pooled specificity was 0.92 (95% CI: 0.89-0.94). The positive likelihood
      ratio was 8.76 (95% CI: 5.41-14.20), the negative likelihood ratio was 0.16 (95%
      CI: 0.13-0. 20) and the diagnostic odds ratio (DOR) was 59.72 (95% CI: 39.60
      90.05). The area under the curve (AUC) for the pleural effusion survivin tests
      was 0.9485, and the *Q index estimate for these tests was 0.8885. CONCLUSIONS:
      Survivin in pleural effusion has potential diagnostic value with advanced
      sensitivity and specificity and it can be used as adjunct tool for non-invasive
      diagnosis of malignant pleural effusion.

PMID- 25559947
TI  - A gender-based approach to developing a healthy lifestyle and healthy weight
      intervention for diverse Utah women.
AB  - Utah women from some cultural minority groups have higher overweight/obesity
      rates than the overall population. We utilized a gender-based mixed methods
      approach to learn about the underlying social, cultural and gender issues that
      contribute to the increased obesity risk among these women and to inform
      intervention development. A literature review and analysis of Utah's Behavioral
      Risk Factor Surveillance System data informed the development of a focus group
      guide. Focus groups were conducted with five groups of women: African immigrants
      from Burundi and Rwanda, African Americans, American Indians/Alaskan Natives,
      Hispanics/Latinas, and Pacific Islanders. Six common themes emerged: (1) health
      is multidimensional and interventions must address health in this manner; (2)
      limited resources and time influence health behaviors; (3) norms about healthy
      weight vary, with certain communities showing more preference to heavier women;
      (4) women and men have important but different influences on healthy lifestyle
      practices within households; (5) women have an influential role on the health of
      families; and (6) opportunities exist within each group to improve health.
      Seeking insights from these five groups of women helped to identify common and
      distinct cultural and gender themes related to obesity, which can be used to help
      elucidate core obesity determinants. 

PMID- 25559948
TI  - Repeated entries to the Swedish addiction compulsory care system: a national
      register database study.
AB  - This study identified and described specific client groups who have repeated
      entries to the Swedish addiction compulsory care system. Specifically, through
      the use of baseline data from the Swedish government Staten's Institutions
      Styrelse (SiS) database, for 2658 individuals who were assessed at their
      compulsory care intake interview by social workers in the national social welfare
      system between 2001 and 2009 the study identified the associations between
      specific predisposing, enabling and need characteristics and repeated addiction
      compulsory care entries. The logistic regression model identified that
      individuals whose children have been mandated to the child welfare system, who
      have experienced prior compulsory care including compulsory treatment through LVU
      (law (1990:52) with specific provision about care of young people under 18), and
      those who have been in prison are more likely to have two or more entries in the
      addiction compulsory care system compared to their counterparts. Individuals who
      have been mandated to compulsory care for their substance use disorder two or
      more times have significant multiple complex problems and repeated experiences of
      institutionalization. These individuals are a group in need of a well-coordinated
      and integrated system of aftercare services to reduce the likelihood of re-entry
      into addiction compulsory care. 

PMID- 25559949
TI  - Collaborating for consensus: Considerations for convening Coalition stakeholders
      to promote a gender-based approach to addressing the health needs of sex workers.
AB  - Women involved in sex work experience myriad challenges, such as poverty,
      illiteracy, low social status and gender inequity, as they struggle to access
      healthcare. These challenges place them at high risk for poor health outcomes.
      The purpose of this article is to describe the formation of a strong cross-system
      Coalition representing both the criminal justice and healthcare systems to
      address the health needs of sex workers in Delaware. The Delaware Coalition for
      Health and Justice implemented a Coalition-building strategy to design
      interventions and streamline systems to promote health and reduce criminal
      justice contact for sex workers. The sequential intercept model was utilized to
      organize Coalition membership and build consensus among varied stakeholders. The
      model assisted the Coalition in understanding differing primary objectives for
      key system programs, recognizing the limitations and barriers of each stakeholder
      group, sharing findings and discovering opportunities for partnership, and
      engaging stakeholders in designing and providing a comprehensive "systems"
      approach. This work suggests that aligning the criminal justice, healthcare, and
      community social services in a systemic process to build consensus can result in
      the implementation of effective systems change initiatives that address gender
      disparities and promote the health of justice-involved women. 

PMID- 25559950
TI  - Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat
      sepsis.

PMID- 25559951
TI  - Epigenetic and metabolic regulation of breast cancer stem cells.
AB  - Breast cancer has a relatively high mortality rate in women due to recurrence and
      metastasis. Increasing evidence has identified a rare population of cells with
      stem cell-like properties in breast cancer. These cells, termed cancer stem cells
      (CSCs), which have the capacity for self-renewal and differentiation, contribute
      significantly to tumor progression, recurrence, drug resistance and metastasis.
      Clarifying the mechanisms regulating breast CSCs has important implications for
      our understanding of breast cancer progression and therapeutics. A strong
      connection has been found between breast CSCs and epithelial mesenchymal
      transition (EMT). In addition, recent studies suggest that the maintenance of the
      breast CSC phenotype is associated with epigenetic and metabolic regulation. In
      this review, we focus on recent discoveries about the connection between EMT and
      CSC, and advances made in understanding the roles and mechanisms of epigenetic
      and metabolic reprogramming in controlling breast CSC properties. 

PMID- 25559954
TI  - Macrophage-produced IL-10 limits the chemotherapy efficacy in breast cancer.

PMID- 25559952
TI  - MicroRNAs in breast cancer: oncogene and tumor suppressors with clinical
      potential.
AB  - MicroRNAs (miRs) are small single-stranded RNA molecules, which function as key
      negative regulators of post-transcriptional modulation in almost all biological
      processes. Abnormal expression of microRNAs has been observed in various types of
      cancer including breast cancer. Great efforts have been made to identify an
      association between microRNA expression profiles and breast cancer, and to
      understand the functional role and molecular mechanism of aberrant-expressed
      microRNAs. As research progressed, 'oncogenic microRNAs' and 'tumor suppressive
      microRNAs' became a focus of interest. The potential of candidate microRNAs from
      both intercellular (tissue) and extracellular (serum) sources for clinical
      diagnosis and prognosis was revealed, and treatments involving microRNA achieved
      some amazing curative effects in cancer disease models. In this review, advances
      from the most recent studies of microRNAs in one of the most common cancers,
      breast cancer, are highlighted, especially the functions of specifically selected
      microRNAs. We also assess the potential value of these microRNAs as diagnostic
      and prognostic markers, and discuss the possible development of microRNA-based
      therapies. 

PMID- 25559953
TI  - Hypoxia-inducible factor 1 and breast cancer metastasis.
AB  - Accumulating evidence has shown that the hypoxic microenvironment, which is
      critical during cancer development, plays a key role in regulating breast cancer
      progression and metastasis. The effects of hypoxia-inducible factor 1 (HIF-1), a
      master regulator of the hypoxic response, have been extensively studied during
      these processes. In this review, we focus on the roles of HIF-1 in regulating
      breast cancer cell metastasis, specifically its effects on multiple key steps of
      metastasis, such as epithelial-mesenchymal transition (EMT), invasion,
      extravasation, and metastatic niche formation. We also discuss the roles of HIF-1
      regulated non-coding RNAs in breast cancer metastasis, and therapeutic
      opportunities for breast cancer through targeting the HIF-1 pathway. 

PMID- 25559955
TI  - Growth effects of botulinum toxin type A injected unilaterally into the masseter
      muscle of developing rats.
AB  - OBJECTIVE: To evaluate the effects of botulinum toxin type A (BTX-A) on mandible
      skeletal development by inducing muscle hypofunction. METHODS: Four-week-old
      Sprague-Dawley rats (n=60) were divided into three groups: Group 1 animals served
      as controls and were injected with saline; Group 2 animals were injected
      unilaterally with BTX-A (the contralateral side was injected with saline); and
      Group 3 animals were injected bilaterally with BTX-A. In Group 2, the saline
      injected side was designated the control side (Group 2-1), whereas the BTX-A
      injected side was designated the experimental side (Group 2-2). After four weeks,
      the animals were sacrificed, dry skulls were prepared, and mandibles were
      measured. RESULTS: In the unilateral group, the experimental side (Group 2-2) had
      reduced dimensions for all mandible measurements compared with the control side
      (Group 2-1), suggesting a local effect of BTX-A on mandible growth, likely due to
      muscle reduction. CONCLUSIONS: Localized BTX-A injection induced a change in
      craniofacial growth, and the skeletal effect was unilateral despite both sides of
      the mandible functioning as one unit.

PMID- 25559956
TI  - Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice.
AB  - BACKGROUND AND AIMS: Ingestion of paraquat (PQ), a widely used herbicide, can
      cause severe toxicity in humans, leading to a poor survival rate and prognosis.
      One of the main causes of death by PQ is PQ-induced pulmonary fibrosis, for which
      there are no effective therapies. The aim of this study was to evaluate the
      effects of rapamycin (RAPA) on inhibiting PQ-induced pulmonary fibrosis in mice
      and to explore its possible mechanisms. METHODS: Male C57BL/6J mice were exposed
      to either saline (control group) or PQ (10 mg/kg body weight, intraperitoneally;
      test group). The test group was divided into four subgroups: a PQ group (PQ
      exposed, non-treated), a PQ+RAPA group (PQ-exposed, treated with RAPA at 1 mg/kg
      intragastrically), a PQ+MP group (PQ-exposed, treated with methylprednisolone
      (MP) at 30 mg/kg intraperitoneally), and a PQ+MP+RAPA group (PQ-exposed, treated
      with MP at 30 mg/kg intraperitoneally and with RAPA at 1 mg/kg intragastrically).
      The survival rate and body weight of all the mice were recorded every day. Three
      mice in each group were sacrificed at 14 d and the rest at 28 d after
      intoxication. Lung tissues were excised and stained with hematoxylin-eosin (H&E)
      and Masson's trichrome stain for histopathological analysis. The hydroxyproline
      (HYP) content in lung tissues was detected using an enzyme-linked immunosorbent
      assay (ELISA) kit. The expression of transforming growth factor-beta1 (TGF-beta1)
      and alpha-smooth muscle actin (alpha-SMA) in lung tissues was detected by
      immunohistochemical staining and Western blotting. RESULTS: A mice model of PQ
      induced pulmonary fibrosis was established. Histological examination of lung
      tissues showed that RAPA treatment moderated the pathological changes of
      pulmonary fibrosis, including alveolar collapse and interstitial collagen
      deposition. HYP content in lung tissues increased soon after PQ intoxication but
      had decreased significantly by the 28th day after RAPA treatment.
      Immunohistochemical staining and Western blotting showed that RAPA treatment
      significantly down-regulated the enhanced levels of TGF-beta1 and alpha-SMA in
      lung tissues caused by PQ exposure. However, RAPA treatment alone could not
      significantly ameliorate the lower survival rate and weight loss of treated mice.
      MP treatment enhanced the survival rate, but had no significant effects on
      attenuating PQ-induced pulmonary fibrosis or reducing the expression of TGF-beta1
      and alpha-SMA. CONCLUSIONS: This study demonstrates that RAPA treatment
      effectively suppresses PQ-induced alveolar collapse and collagen deposition in
      lung tissues through reducing the expression of TGF-beta1 and alpha-SMA. Thus,
      RAPA has potential value in the treatment of PQ-induced pulmonary fibrosis.

PMID- 25559957
TI  - Chronic corticosterone exposure reduces hippocampal glycogen level and induces
      depression-like behavior in mice.
AB  - Long-term exposure to stress or high glucocorticoid levels leads to depression
      like behavior in rodents; however, the cause remains unknown. Increasing evidence
      shows that astrocytes, the most abundant cells in the central nervous system
      (CNS), are important to the nervous system. Astrocytes nourish and protect the
      neurons, and serve as glycogen repositories for the brain. The metabolic process
      of glycogen, which is closely linked to neuronal activity, can supply sufficient
      energy substrates for neurons. The research team probed into the effects of
      chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the
      hippocampal tissues of male C57BL/6N mice in this study. The results showed that
      chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and
      synaptophysin (SYP) levels, induced depression-like behavior in male mice,
      reduced hippocampal glycogen level and glycogen synthase activity, and increased
      glycogen phosphorylase activity. The results suggested that the reduction of the
      hippocampal glycogen level may be the mechanism by which chronic CORT treatment
      damages hippocampal neurons and induces depression-like behavior in male mice. 

PMID- 25559958
TI  - Epidemiology and microbiology of nosocomial bloodstream infections: analysis of
      482 cases from a retrospective surveillance study.
AB  - In many traditional Chinese medicine (TCM) hospitals, most patients are elderly
      with chronic diseases. Nosocomial bloodstream infections (nBSIs) are an important
      cause of morbidity and mortality. A retrospective surveillance study was
      performed to examine the epidemiology and microbiology of nBSIs in a TCM hospital
      from 2009 to 2011. A total of 482 patients with nBSIs were included in the study
      period. The incidence rate was 5.7/1000 admissions. Escherichia coli (25.5%) was
      the most common Gram-negative and coagulase-negative staphylococcus (CoNS)
      (14.1%) was the most common Gram-positive organism isolated. One-third of the E.
      coli and Klebsiella pneumoniae isolated from the nBSIs were the third-generation
      cephalosporin-resistant. Half of the Acinetobacter species isolates were
      resistant to imipenem. Of all the CoNS isolates, 90.7% were resistant to
      methicillin. Carbapenems and glycopeptide were the most frequently used for nBSI
      therapy. Only about one-third of patients (157/482) received appropriate
      empirical therapy. Septic shock, hemodialysis, Pitt bacteremia score >4, urinary
      tract infection, and appropriate empirical therapy were most strongly associated
      with 28-d mortality. The incidence of nBSIs was low in the TCM hospital but the
      proportion of nBSIs due to antibiotic-resistant organisms was high. A high Pitt
      bacteremia score was one of the most important risk factors for mortality in
      nBSIs. Therefore, the implementation of appropriate empirical therapy is crucial
      to improve the clinical outcome of nBSIs. 

PMID- 25559960
TI  - Focusing in on applications.

PMID- 25559959
TI  - Elevated homocysteine levels and risk of cardiovascular and all-cause mortality:
      a meta-analysis of prospective studies.
AB  - OBJECTIVE: To investigate whether elevated homocysteine levels were a predictor
      of subsequent coronary heart disease (CHD) mortality, cardiovascular mortality or
      all-cause mortality in the general population by a meta-analysis. METHODS: In a
      systematic search conducted in the databases of PubMed and Embase prior to
      October 2013, we identified relevant prospective observational studies evaluating
      the association between baseline homocysteine levels and CHD mortality,
      cardiovascular or all-cause mortality in the general population. Pooled adjust
      risk ratio (RR) and corresponding 95% confidence interval (CI) were calculated
      separately for categorical risk estimates and continuous risk estimates. RESULTS:
      Twelve studies with 23623 subjects were included in the meta-analysis. Comparing
      the highest to lowest homocysteine level categories, CHD mortality increased by
      66% (RR 1.66; 95% CI 1.12-2.47; P=0.012), cardiovascular mortality increased by
      68% (RR 1.68; 95% CI 1.04-2.70; P=0.033), and all-cause mortality increased by
      93% (RR 1.93; 95% CI 1.54-2.43; P<0.001). Moreover, for each 5 MUmol/L
      homocysteine increment, the pooled RR was 1.52 (95% CI 1.26-1.84; P<0.001) for
      CHD mortality, 1.32 (95% CI 1.08-1.61; P=0.006) for cardiovascular mortality, and
      1.27 (95% CI 1.03-1.55; P=0.023) for all-cause mortality. CONCLUSIONS: Elevated
      homocysteine levels are an independent predictor for subsequent cardiovascular
      mortality or all-cause mortality, and the risks were more pronounced among
      elderly persons.

PMID- 25559962
TI  - The case for plasmon-derived hot carrier devices.

PMID- 25559961
TI  - How to deal with the loss in plasmonics and metamaterials.

PMID- 25559963
TI  - From science to policy.

PMID- 25559964
TI  - Nano-optics gets practical.

PMID- 25559965
TI  - Colouring at the nanoscale.

PMID- 25559967
TI  - Photoelectrochemical water splitting: A new use for bandgap engineering.

PMID- 25559968
TI  - Plasmon-induced hot carrier science and technology.
AB  - The discovery of the photoelectric effect by Heinrich Hertz in 1887 set the
      foundation for over 125 years of hot carrier science and technology. In the early
      1900s it played a critical role in the development of quantum mechanics, but even
      today the unique properties of these energetic, hot carriers offer new and
      exciting opportunities for fundamental research and applications. Measurement of
      the kinetic energy and momentum of photoejected hot electrons can provide
      valuable information on the electronic structure of materials. The heat generated
      by hot carriers can be harvested to drive a wide range of physical and chemical
      processes. Their kinetic energy can be used to harvest solar energy or create
      sensitive photodetectors and spectrometers. Photoejected charges can also be used
      to electrically dope two-dimensional materials. Plasmon excitations in metallic
      nanostructures can be engineered to enhance and provide valuable control over the
      emission of hot carriers. This Review discusses recent advances in the
      understanding and application of plasmon-induced hot carrier generation and
      highlights some of the exciting new directions for the field. 

PMID- 25559970
TI  - A lesson in student chapters.

PMID- 25559969
TI  - Erratum: Squalenoyl adenosine nanoparticles provide neuroprotection after stroke
      and spinal cord injury.

PMID- 25559971
TI  - Apoptosis and associated phenomena as a determinants of the efficacy of
      photodynamic therapy.
AB  - Failure of neoplastic cells to respond to conventional chemotherapy is usually
      associated with factors that limit access of drugs to subcellular sites,
      differences in cell-cycle kinetics or mutations leading to loss of drug
      activation pathways or other processes that govern response factors. For PDT,
      efficacy depends mainly on selective uptake of photosensitizers by neoplastic
      cells, oxygenation levels, the suitable direction of irradiation and the
      availability of pathways to cell death that are highly conserved among mammalian
      cell types. While it is possible to engineer PDT-resistant cell types, current
      evidence suggests that the major obstacles to cancer control relate to drug,
      light and oxygen distribution. This review discusses some of the factors that can
      govern PDT-induced cell death. 

PMID- 25559973
TI  - Calculation of the vibrational frequencies of carbon clusters and fullerenes with
      empirical potentials.
AB  - Vibrational frequencies for carbon clusters, fullerenes and nanotubes evaluated
      using empirical carbon-carbon potentials are presented. For linear and cyclic
      clusters, frequencies evaluated with the reactive empirical bond order (REBO)
      potential provide the closest agreement with experiment. The mean absolute
      deviation (MAD) between experiment and the calculated harmonic frequencies is 79
      cm(-1) for the bending modes and 76 cm(-1) for the stretching modes. The effects
      of anharmonicity are included via second order vibrational perturbation theory
      and tend to increase the frequency of the bending modes while the stretching
      modes have negative shifts in the region of 20-60 cm(-1), with larger shifts for
      the higher frequency modes. This results in MADs for the bending and stretching
      modes of 84 cm(-1) and 58 cm(-1), respectively. For the fullerene molecule C60,
      the high frequency modes are predicted to have harmonic frequencies that are
      significantly higher than experiment, and this is not corrected by accounting for
      anharmonicity. This overestimation of experimental observed frequencies is also
      evident in the calculated frequencies of the G band in nanotubes. This suggests
      that the REBO potential is not optimal for these larger systems and it is shown
      that adjustment of the parameters within the potential leads to closer agreement
      with experiment, particularly if higher and lower frequency modes are considered
      separately. 

PMID- 25559974
TI  - Investigation of the effect of conservative interventions in thumb
      carpometacarpal osteoarthritis: systematic review and meta-analysis.
AB  - PURPOSE: The purpose of this study was to conduct a current review of randomized
      controlled trials regarding the effect of conservative interventions on pain and
      function in people with thumb carpometacarpal (CMC) osteoarthritis (OA), perform
      a meta-analysis of the findings and summarize current knowledge. METHOD: Data
      were obtained from MEDLINE, CINAHL, Embase, PEDro and CENTRAL databases from
      their inception to May 2014. Reference lists of relevant literature reviews were
      also searched. All published randomized trials without restrictions to time of
      publication or language were considered for inclusion. Study subjects were
      symptomatic adults with thumb CMC OA. Two reviewers independently selected
      studies, conducted quality assessment and extracted results. Data were pooled in
      a meta-analysis, when possible, using a random-effects model. Quality of the body
      evidence was assessed using GRADE approach. RESULTS: Sixteen RCTs involving 1145
      participants met the inclusion criteria. Twelve were of high quality (PEDro score
      > 6). We found moderate quality evidence that manual therapy and therapeutic
      exercise combined with manual therapy improve pain in thumb CMC OA at short- and
      intermediate-term follow-up, and from low to moderate quality evidences that
      magneto therapy improves pain and function at short-term follow-up. Orthoses
      (splints) were found to improve function at long-term follow-up and pinch
      strength at short-term follow-up. Finally, we found from very low to low-quality
      evidence that other conservative interventions provide no significant improvement
      in pain and in function at short- and long-term follow-up. CONCLUSIONS: Some of
      the commonly performed conservative interventions performed in therapy have
      evidence to support their use to improve hand function and decrease hand pain.
      Additional research is required to determine the efficacy of other therapeutic
      interventions that are performed with patients with thumb CMC OA. IMPLICATIONS
      FOR REHABILITATION: Manual therapy and exercise are an effective means of
      improving pain and function at short-term follow-up by patients with thumb CMC
      OA. Magneto therapy, manual therapy, manual therapy and exercise and Orthoses
      (splints) were found to have clinically significant results. Very few of the
      included studies showed a clinically significant effect size in favor of
      treatment.

PMID- 25559975
TI  - Differences in carbon isotope signatures of polyunsaturated fatty acids of two
      microalgal species.

PMID- 25559972
TI  - Membrane-active peptides from marine organisms--antimicrobials, cell-penetrating
      peptides and peptide toxins: applications and prospects.
AB  - Marine organisms are known to be a rich and unique source of bioactive compounds
      as they are exposed to extreme conditions in the oceans. The present study is an
      attempt to briefly describe some of the important membrane-active peptides (MAPs)
      such as antimicrobial peptides (AMPs), cell-penetrating peptides (CPPs) and
      peptide toxins from marine organisms. Since both AMPs and CPPs play a role in
      membrane perturbation and exhibit interchangeable role, they can speculatively
      fall under the broad umbrella of MAPs. The study focuses on the structural and
      functional characteristics of different classes of marine MAPs. Further, AMPs are
      considered as a potential remedy to antibiotic resistance acquired by several
      pathogens. Peptides from marine organisms show novel post-translational
      modifications such as cysteine knots, halogenation and histidino-alanine bridge
      that enable these peptides to withstand harsh marine environmental conditions.
      These unusual modifications of AMPs from marine organisms are expected to
      increase their half-life in living systems, contributing to their increased
      bioavailability and stability when administered as drug in in vivo systems. Apart
      from AMPs, marine toxins with membrane-perturbing properties could be essentially
      investigated for their cytotoxic effect on various pathogens and their cell
      penetrating activity across various mammalian cells. The current review will help
      in identifying the MAPs from marine organisms with crucial post-translational
      modifications that can be used as template for designing novel therapeutic agents
      and drug-delivery vehicles for treatment of human diseases. 

PMID- 25559976
TI  - The influence of bromocryptine treatment on activity of the adenylyl cyclase
      system in the brain of rats with type 2 diabetes mellitus induced by high-fat
      diet.

PMID- 25559977
TI  - Effects of low concentrations of synthetic antioxidant phenosan potassium salt on
      the thermoinduced structural transitions in the protein component of plasma
      membranes.

PMID- 25559978
TI  - The role of water bugs (Heteroptera) as a potential source of essential
      polyunsaturated fatty acids for terrestrial consumers in steppe and forest
      steppe.

PMID- 25559979
TI  - Mechanisms of anomalous temperature dependence of the recombination of the
      photoseparated charges between bacteriochlorophyll and primary quinone in Rb.
      sphaeroides: The role of RC hydrogen bonds.

PMID- 25559980
TI  - The promoter activation at the end of terminally truncated chromosome in
      Drosophila melanogaster.

PMID- 25559981
TI  - Introduction of ISSR markers for Kamchatka mykiss (Parasalmo (Oncorhynchus)
      mykiss) (Walbaum) (Salmonidae, Salmoniformes).

PMID- 25559982
TI  - Expression of calsarcin isoforms and myosin phenotype stabilization in
      transitional unloaded muscle.

PMID- 25559983
TI  - The glucosinolate metabolite 1-methoxy-3-indolylmethyl alcohol induces a gene
      expression profile in mouse liver similar to the expression signature caused by
      known genotoxic hepatocarcinogens.
AB  - SCOPE: Breakdown products of certain glucosinolates induce detoxifying enzymes
      and demonstrate preventive activities against chemically induced tumourigenesis
      in animal models. However, other breakdown products are genotoxic. 1-Methoxy-3
      indolylmethyl alcohol (1-MIM-OH) is mutagenic in bacterial and mammalian cells
      upon activation by sulphotransferases and forms DNA adducts in mouse tissues.
      This effect is enhanced in mice transgenic for human sulphotransferases 1A1/2
      (FVB/N-hSULT1A1/2). Therefore, we explored gene expression changes induced by 1
      MIM-OH in mouse liver. METHODS AND RESULTS: FVB/N-hSULT1A1/2 mice were orally
      treated with 1-MIM-OH for 21 or 90 days, leading to high levels of hepatic 1-MIM
      DNA adducts. Genome-wide expression analyses demonstrated no influence on
      detoxifying enzymes, but up-regulation of many mediators of the tumour suppressor
      p53 and down-regulation of Fhit and other long genes. While this p53 response
      might indicate protection, it was unable to prevent the accumulation of DNA
      adducts. However, various epidemiological studies reported inverse associations
      between the intake of cruciferous vegetables and cancer. This association may be
      due to the presence of other glucosinolates with tumour-preventing influences
      possibly outweighing adverse effects of some metabolites. CONCLUSION: 1-MIM-OH is
      a genotoxic substance inducing a gene expression profile similar to the
      expression signature caused by known genotoxic hepatocarcinogens.

PMID- 25559984
TI  - Right posterior segment graft in living donor liver transplantation.
AB  - AIM: Living donor liver transplantation (LDLT) is widely performed for end-stage
      liver disease. Liver volume is important for donor safety and recipient survival.
      In adult-to-adult LDLT, left lobe graft is frequently insufficient for the
      recipient, while right lobe graft carries a higher donor risk. The right
      posterior segment graft (RPSG) was introduced to increase donor selection
      options. However, only a few institutions have reported LDLT with an RPSG.
      METHODS: In total, 587 adult recipients underwent LDLT at Kyoto University
      Hospital from 2001 to 2011. Here, we retrospectively report 14 LDLT with RPSG.
      All donors underwent volumetric analyses and detailed investigation of the
      hepatic vein (HV), portal vein (PV), hepatic artery (HA) and biliary duct (BD).
      Anatomical anomalies were detected in four donors' BD. The mean Model for End
      Stage Liver Disease score was 22.6 +/- 12.4 points. ABO blood groups were
      characterized as incompatible in three cases. The mean graft-to-recipient weight
      ratio was 0.897 +/- 0.203. RESULTS: Donors' postoperative courses were
      uneventful. To adjust diameters and lengths between grafts and recipients, dual
      anastomoses for PV reconstruction and graft interpositions for PV and HA
      reconstruction were required in one case each. HA thrombosis occurred in two
      cases and PV thrombosis in one. Biliary complications occurred in two cases.
      Though there was no significant difference in survival following RPSG versus
      other grafts, critical complications were observed in recipients. CONCLUSION: The
      RPSG is a useful option in LDLT. However, careful consideration is required for
      RPSG harvest and LDLT performance, both before and during surgery.

PMID- 25559985
TI  - Consolidation hyperthermic intraperitoneal chemotherapy and maintenance
      chemotherapy following laparoscopic cytoreductive surgery in the treatment of
      ovarian carcinoma.
AB  - PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) is an intriguing
      method of delivery wherein the cytotoxic agent is continuously heated and
      circulated throughout the peritoneum in an attempt to improve efficacy. Despite
      the potential of HIPEC in the treatment of ovarian cancer, there are limited
      safety, feasibility and survival data involving this procedure, particularly in
      conjunction with maintenance chemotherapy. PATIENTS AND METHODS: We
      retrospectively evaluated ovarian cancer patients who underwent laparoscopic
      debulking surgery, attained a complete response to their primary chemotherapy and
      subsequently received consolidation HIPEC with carboplatin area under the curve
      of 10 (AUC of 10) and a planned 12 cycles of paclitaxel (135 mg/m(2)) maintenance
      chemotherapy. The following demographic and clinical characteristics were
      abstracted: patient age, body mass index, surgery and pathology data,
      chemotherapy regimen, intra-operative results, toxicity, post-operative
      complications, length of hospital stay and disease-free/overall survival.
      RESULTS: We identified 37 patients who were the subject of this study. There were
      no intra-operative complications during the administration of HIPEC; median
      estimated blood loss was 50 mL and length of hospital stay was 1.25 days. In the
      overall study population, six patients developed grade 3/4 anaemia and 24
      patients exhibited grade <= 2 thrombocytopenia and neutropenia. Ten patients
      developed grade <= 2 nausea on postoperative day 1; there were no hospital
      readmissions. Median disease-free survival and overall survival was 13 months and
      14 months, respectively. CONCLUSION: The results from this ovarian cancer
      treatment evaluation suggest that the combination of consolidation HIPEC and
      maintenance chemotherapy is feasible and reasonably well tolerated.

PMID- 25559986
TI  - Top-down 193-nm ultraviolet photodissociation mass spectrometry for simultaneous
      determination of polyubiquitin chain length and topology.
AB  - Protein ubiquitin modifications present a vexing analytical challenge, because of
      the dynamic changes in the site of modification on the substrate, the number of
      ubiquitin moieties attached, and the diversity of linkage patterns in which they
      are attached. Presented here is a method to confidently assign size and linkage
      type of polyubiquitin modifications. The method combines intact mass measurement
      to determine the number of ubiquitin moieties in the chain with backbone
      fragmentation by 193-nm ultraviolet photodissociation (UVPD) to determine the
      linkage pattern. UVPD fragmentation of proteins leads to reproducible backbone
      cleavage at almost every inter-residue position, and in polyubiquitin chains, the
      N-terminally derived fragments from each constituent monomer are identical, up to
      the site of conjugation. The N-terminal ubiquitin fragment ions are superimposed
      to create a diagnostic pattern that allows easy recognition of the dominant chain
      linkages. The method is demonstrated by achieving almost-complete fragmentation
      of monoubiquitin and then, subsequently, fragmentation of dimeric, tetrameric,
      and longer Lys48- and Lys63-linked ubiquitin chains. The utility of the method
      for the analysis of mixed linkage chains is confirmed for mixtures of Lys48 and
      Lys63 tetramers with known relative concentrations and for an in vitro-formulated
      ubiquitin chain attached to a substrate protein. 

PMID- 25559989
TI  - A perspective on cancer as an abortive autoimmune response to altered-self.

PMID- 25559987
TI  - Improving miRNA-mRNA interaction predictions.
AB  - BACKGROUND: MicroRNAs are short RNA molecules that post-transcriptionally
      regulate gene expression. Today, microRNA target prediction remains challenging
      since very few have been experimentally validated and sequence-based predictions
      have large numbers of false positives. Furthermore, due to the different
      measuring rules used in each database of predicted interactions, the selection of
      the most reliable ones requires extensive knowledge about each algorithm.
      RESULTS: Here we propose two methods to measure the confidence of predicted
      interactions based on experimentally validated information. The output of the
      methods is a combined database where new scores and statistical confidences are
      re-assigned to each predicted interaction. The new scores allow the robust
      combination of several databases without the effect of low-performing algorithms
      dragging down good-performing ones. The combined databases obtained using both
      algorithms described in this paper outperform each of the existing predictive
      algorithms that were considered for the combination. CONCLUSIONS: Our approaches
      are a useful way to integrate predicted interactions from different databases.
      They reduce the selection of interactions to a unique database based on an
      intuitive score and allow comparing databases between them.

PMID- 25559990
TI  - 16-hour call duty schedules: the Quebec experience.
AB  - Since 1 July 2012, as a result of a labour arbitration ruling in the province of
      Quebec and the subsequent agreement negotiated by the Federation des medecins
      residents du Quebec, all 3,400 medical residents training in Quebec have been on
      a 16-hour duty schedule for in-house calls. This is a major change within medical
      teaching sites, as well as a professional and educational challenge for
      physicians-in-training and their supervisors. The Quebec ruling now raises
      similar issues for all medical residents in Canada because of its legal basis,
      namely the Canadian Charter of Rights and Freedoms. 

PMID- 25559991
TI  - Determination of the 95% effective dose of remifentanil for the prevention of
      coughing during extubation in children undergoing tonsillectomy (with or without
      adenoidectomy).
AB  - BACKGROUND: Limited data are available regarding the 95% effective dose (ED95 )
      of remifentanil to prevent the cough response during emergence from general
      anesthesia in children. METHODS: This study included 40 patients aged 3-12 years
      who underwent elective tonsillectomy with or without adenoidectomy. A
      predetermined remifentanil dose was infused continuously with desflurane during
      surgery and was continued until extubation. In the emergence period, the cough
      response during awake extubation was assessed to determine the remifentanil dose
      for the next patient. The first patient received remifentanil at the rate of 0.01
      MUg.kg(-1) .min(-1) , and subsequent patients received a 0.01 MUg.kg(-1) .min(-1)
      higher dose than the previous patient if there was more than moderate coughing
      detected, and the patient after those with less than mild coughing received
      either the same dose (95% probability) or a 0.01 MUg.kg(-1) .min(-1) lower dose
      (5% probability) using the biased coin design. Times to extubation and adverse
      events were recorded. The ED95 was calculated using the maximum-likelihood
      estimation. RESULTS: The ED95 of remifentanil for preventing coughing during
      extubation was 0.060 MUg.kg(-1) .min(-1) (95% confidence interval, 0.037-0.068).
      There was moderate coughing in all groups receiving 0.01-0.06 MUg.kg(-1) .min(-1)
      of remifentanil, but no cough response occurred in the group receiving
      remifentanil 0.07 MUg.kg(-1) .min(-1) . Time to extubation was weakly correlated
      with remifentanil infusion rate (r = 0.331). One patient who received
      remifentanil 0.07 MUg.kg(-1) .min(-1) showed desaturation over 5 s immediately
      after extubation, but recovered after receiving 100% oxygen. CONCLUSION: The ED95
      of the continuous remifentanil infusion rate was 0.060 MUg.kg(-1) .min(-1) to
      prevent the cough response during extubation in children after tonsillectomy.

PMID- 25559992
TI  - The role of antimicrobials in the treatment of sepsis and critical illness
      related bacterial infections: examination of the evidence.
AB  - OBJECTIVE: To appraise the evidence behind the Surviving Sepsis Campaign
      Guidelines on antimicrobial therapy in sepsis and evaluate relevant literature in
      small animal veterinary critical care. DATA SOURCE: Electronic searches using
      MEDLINE and EMBASE databases. HUMAN DATA SYNTHESIS: Current recommendations are
      to administer appropriate antimicrobials within 1 hour of a diagnosis of severe
      sepsis or septic shock. Evidence is supportive of this recommendation in septic
      shock but the evidence is less compelling in milder forms of critical illness
      related infections. It is unclear when the administration of appropriate
      antimicrobials is most beneficial and when it should be considered essential.
      Evidence supports shorter courses of antimicrobial therapy for many infections
      seen in the critical care unit with the biomarkers procalcitonin and C-reactive
      protein helpful in guiding the duration of therapy. VETERINARY DATA SYNTHESIS:
      Current evidence is lacking to support the use of early and aggressive use of
      antimicrobials in all patients with critical illness-related bacterial
      infections. Two studies failed to demonstrate improved survival in patients with
      pulmonary or abdominal infections administered appropriate vs inappropriate
      empirical antimicrobials. One study failed to show an improved survival when dogs
      with abdominal infections were administered antimicrobials within 1 hour vs 6
      hours of diagnosis of infection. Information regarding ideal duration of
      antimicrobial therapy and use of biomarkers to guide therapy is currently
      lacking. CONCLUSION: Clinicians should aim to administer early and appropriate
      antimicrobials; however, the impact this will have on patient outcome remains
      uncertain. The ability to administer early and appropriate antimicrobials may be
      considered a measure of the quality of medical practice rather than a prognostic
      indicator.

PMID- 25559993
TI  - Probing structural dynamics of an artificial protein cage using high-speed atomic
      force microscopy.
AB  - A cysteine-substituted mutant of the ring-shaped protein TRAP (trp-RNA binding
      attenuation protein) can be induced to self-assemble into large, monodisperse
      hollow spherical cages in the presence of 1.4 nm diameter gold nanoparticles. In
      this study we use high-speed atomic force microscopy (HS-AFM) to probe the
      dynamics of the structural changes related to TRAP interactions with the gold
      nanoparticle as well as the disassembly of the cage structure. The dynamic
      aggregation of TRAP protein in the presence of gold nanoparticles was observed,
      including oligomeric rearrangements, consistent with a role for gold in mediating
      intermolecular disulfide bond formation. We were also able to observe that the
      TRAP-cage is composed of multiple, closely packed TRAP rings in an apparently
      regular arrangement. A potential role for inter-ring disulfide bonds in forming
      the TRAP-cage was shown by the fact that ring-ring interactions were reversed
      upon the addition of reducing agent dithiothreitol. A dramatic disassembly of
      TRAP-cages was observed using HS-AFM after the addition of dithiothreitol. To the
      best of our knowledge, this is the first report to show direct high-resolution
      imaging of the disassembly process of a large protein complex in real time. 

PMID- 25559994
TI  - Need to rationalize linezolid use.

PMID- 25559995
TI  - Dengue vaccines: challenges, development, current status and prospects.
AB  - Infection with dengue virus (DENV) is the most rapidly spreading mosquito-borne
      viral disease in the world. The clinical spectrum of dengue, caused by any of the
      four serotypes of DENV, ranges from mild self-limiting dengue fever to severe
      dengue, in the form dengue hemorrhagic fever (DHF) and dengue shock syndrome
      (DSS). Increased rates of hospitalization due to severe dengue, during outbreaks,
      result in massive economic losses and strained health services. In the absence of
      specific antiviral therapy, control of transmission of DENV by vector management
      is the sole method available for decreasing dengue-associated morbidity. Since
      vector control strategies alone have not been able to satisfactorily achieve
      reduction in viral transmission, the implementation of a safe, efficacious and
      cost-effective dengue vaccine as a supplementary measure is a high public health
      priority. However, the unique and complex immunopathology of dengue has
      complicated vaccine development. Dengue vaccines have also been challenged by
      critical issues like lack of animal models for the disease and absence of
      suitable markers of protective immunity. Although no licensed dengue vaccine is
      yet available, several vaccine candidates are under phases of development,
      including live attenuated virus vaccines, live chimeric virus vaccines,
      inactivated virus vaccines, subunit vaccines, DNA vaccines and viral-vectored
      vaccines. Although some vaccine candidates have progressed from animal trials to
      phase II and III in humans, a number of issues regarding implementation of dengue
      vaccine in countries like India still need to be addressed. Despite the current
      limitations, collaborative effects of regulatory bodies like World Health
      Organization with vaccine manufacturers and policy makers, to facilitate vaccine
      development and standardize field trials can make a safe and efficacious dengue
      vaccine a reality in near future. 

PMID- 25559996
TI  - Tumour necrosis factor-alpha promoter polymorphism and its association with viral
      dilated cardiomyopathy in Indian population: a pilot study.
AB  - PURPOSE: Tumour necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine
      has been implicated in the pathophysiology of several viral infections. TNF-alpha
      promoter gene polymorphism is thus believed to play the modulating role in this
      disease pathogenesis. Several studies have shown the increased level of TNF-alpha
      in dilated cardiomyopathy (DCM). However, the role of the TNF-alpha promoter
      polymorphism is yet to be delineated in this regard. The present study for the
      first time tried to explore the association of TNF-alpha gene polymorphism with
      DCM of viral aetiology. MATERIALS AND METHODS: Eighteen histopathologically
      proven DCM cases with viral genome positivity and 17 healthy controls were
      genotyped using polymerase chain reaction of TNF-alpha promoter gene followed by
      restriction fragment length polymorphism to determine the SNPs of -238G/A, 
      308G/A, -857C/T and -863C/A. RESULTS: Of the 18 DCM cases 4 (22.2%) were positive
      for adenovirus (AdV), 2 (11.1%) for enterovirus (EV) and 12 (66.7%) had co
      infection. Six of the 18 DCM cases (35.3%) had -238G/A polymorphism, and 10
      (55.5%) had -863 homozygous AA genotype. The association of these polymorphisms
      was statistically significant as compared to controls (P < 0.05). CONCLUSIONS:
      The present pilot study suggests the possible association of TNFalpha -238G/A and
      -863C/A polymorphism with DCM of viral aetiology.

PMID- 25559997
TI  - Detection of the classical G2576U mutation in linezolid resistant Staphylococcus
      aureus along with isolation of linezolid resistant Enterococcus faecium from a
      patient on short-term linezolid therapy: first report from India.
AB  - PURPOSE: Linezolid is an effective drug against methicillin-resistant
      Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). We
      describe the emergence of linezolid resistance in MRSA and VRE from India.
      MATERIAL AND METHODS: One MRSA and two VRE strains were isolated from a patient
      on linezolid therapy of one week duration. All three isolates were resistant to
      linezolid with minimal inhibitory concentrations (MIC) >=4 mg/L. The 746-bp
      region flanking the possible G2576U mutation on the corresponding DNA from the
      23S rRNA was amplified by polymerase chain reaction (PCR) and amplicons were
      sequenced for all the three isolates. Conjugation experiments using the linezolid
      resistant MRSA (LRMRSA) and linezolid resistant VRE (LRVRE) isolates as donors
      and wild strains of corresponding genera as recipients were performed. RESULTS:
      The MRSA isolate had the classical G2576U mutation. High quality value scores in
      the sequencing software validated the mutation. Conjugation studies did not
      indicate presence of transferable resistance for linezolid. Sequencing did not
      indicate presence of any mutation in the two LRVRE isolates. CONCLUSIONS: This is
      the first report from India citing resistance in Staphylococcus and Enterococcus
      against Linezolid.

PMID- 25559998
TI  - Changing paradigm of cryptococcal meningitis: an eight-year experience from a
      tertiary hospital in South India.
AB  - BACKGROUND: Cryptococcal meningitis (CM) is a common opportunistic fungal
      infection causing sub-acute meningitis with the potential for complications and
      significant mortality. We conducted this study to describe the difference in
      presentation and outcome between HIV-infected and HIV-uninfected patients.
      MATERIALS AND METHODS: Patients admitted to a tertiary care centre between 2005
      and 2013 with confirmed CM were included in the analysis. Details of the clinical
      presentation, laboratory findings, treatment details, risk factors for infection
      and outcome were documented and analysed. RESULTS: During the study period, 102
      (87.2%) cases of CM occurred among HIV infected individuals, whereas 15 (12.8%)
      occurred among HIV-uninfected patients. HIV-infected patients with CM were
      younger compared with HIV-uninfected patients (38.2 +/- 8.5 years vs. 45 +/- 11.5
      years; P = 0.07). The median duration of symptoms prior to presentation was
      shorter in the HIV-infected group (20 +/- 32 vs. 30 +/- 42; P = 0.03). There was
      no difference between the cerebrospinal fluid (CSF) lymphocyte counts, CSF
      protein counts, and CSF sugar levels in both the groups. The diagnostic yield of
      Cryptococcus was similar with CSF India ink smear (89% vs. 87%), CSF fungal
      culture (95% vs. 87%), and blood culture (100% vs. 75%) in both the groups. Case
      fatality rate in the HIV-infected group was 30.6%, whereas there were no deaths
      in the HIV-uninfected group. CONCLUSION: HIV-infected patients with CM have a
      worse outcome compared to HIV-uninfected patients. The overall trend over 3
      decades shows increasingly successful rates of treatment and hence early
      diagnosis and treatment are of paramount importance.

PMID- 25559999
TI  - Complete sequencing of an IncX3 plasmid carrying blaNDM-5 allele reveals an early
      stage in the dissemination of the blaNDM gene.
AB  - PURPOSE: The aim of the present study was to perform molecular characterisation
      of the blaNDM plasmids and to understand the mechanism of its spread among
      pathogenic bacteria. MATERIALS AND METHODS: Seventy-six non-repetitive carbapenem
      resistant isolates which were collected during Nov 2011 to April 2013 from four
      hospitals in Chennai were analyzed for the presence of the blaNDM gene by PCR.
      Further, the genetic context of the blaNDM gene was analyzed by PCR specific to
      ISAba125 and bleMBL gene. One of the blaNDM plasmid was completely sequenced in
      the Illumina HiSeq platform. RESULTS: Twenty-three isolates consisting of 8
      Escherichia coli, 8 Klebsiella pneumoniae, 3 Klebsiella oxytoca, 3 Acinetobacter
      baumanii and 1 Pseudomonas aeruginosa were found to carry the blaNDM gene. In 18
      isolates the blaNDM gene was associated with a bleMBL gene and the ISAba125
      element. The complete sequencing of pNDM-MGR194 revealed an IncX3 replication
      type plasmid, with a length of 46,253 bp, an average GC content of 47% and 59
      putative ORFs. The iteron region contained the blaNDM5 gene and the bleMBL , trpF
      and dsbC genes downstream and an IS5 inserted within the ISAba125 element
      upstream. CONCLUSION: This is the first report where the blaNDM gene insertion in
      a plasmid is not accompanied by other resistance gene determinants. These
      observations suggest that the IncX3 plasmid pNDM-MGR194 is an early stage in the
      dissemination of the blaNDM .

PMID- 25560000
TI  - Rising trend of antimicrobial resistance among Neisseria gonorrhoeae isolates and
      the emergence of N. gonorrhoeae isolate with decreased susceptibility to
      ceftriaxone.
AB  - CONTEXT: Gonorrhoea is one of the most common sexually transmitted infections
      (STI) in developing countries and is a global health problem. AIMS: To analyze
      the trend of antimicrobial susceptibility of Neisseria gonorrhoeae isolates over
      the years, in a tertiary care hospital of North India. SETTINGS AND DESIGN: The
      study population comprised males with urethritis and females with endocervicitis
      attending STI clinic of our hospital. MATERIALS AND METHODS: In our STI
      laboratory, all gonococcal isolates are subjected to antimicrobial susceptibility
      testing by disc diffusion method as per CLSI guidelines. beta-Lactamase
      production is determined by chromogenic cephalosporin test. Minimum Inhibitory
      Concentration (MIC) for ceftriaxone is determined by E-test. STATISTICAL ANALYSIS
      USED: Data were expressed as percentages. The differences in percentages were
      tested for statistical significance by using chi2 test and P values were
      determined. RESULTS: The percentage of penicillinase producing N. gonorrhoeae
      (PPNG) increased from 8% in 1995-96 to 20% in 2004-05 and 88% in 2011-2013.
      Quinolone-resistant N. gonorrhoeae (QRNG) showed a significant increase from 12%
      in 1995-96 to 98.3% in 2004-05, while 84% isolates were found to be QRNG by 2011
      2013. In January 2013 we detected our first gonococcal isolate with decreased
      susceptibility to third-generation cephalosporins; Ceftriaxone, Cefixime and
      Cefpodoxime (MIC for ceftriaxone = 0.19 MUg/ml). CONCLUSIONS: The results of our
      study highlighted an alarming increase in the percentage of PPNG and QRNG strains
      over the years. Emergence of N. gonorrhoeae isolates with decreased
      susceptibility to third-generation cephalosporins is a cause of concern and thus
      emphasises the importance of antimicrobial susceptibility testing.

PMID- 25560001
TI  - Surveillance of acute respiratory infections in Mumbai during 2011-12.
AB  - PURPOSE: Acute respiratory infections (ARIs) are a leading cause of morbidity and
      mortality in individuals aged less than 5 years. ARI often leads to
      hospitalisation, and it has been indicated that causative viral and bacterial
      infections go undetermined and results in the occurrence of resistant strains.
      The objective of the study was to assess the prevalence of various viral and
      bacterial infections in patients with ARIs. MATERIALS AND METHODS: Two hundred
      samples were collected from July 2011 to July 2012 with patients suffering from
      ARI. Viral and bacterial infections were determined by real time reverse
      transcriptase polymerase chain reaction. RESULTS: Influenza-like illness (ILI)
      consisted of 109 patients and ARI consisted of 91 patients. Pandemic influenza A
      H1N1 was the major viral infection with 21 (19.2%) patients in ILI as compared
      with 16 (17.4%) patients in ARI. Respiratory syncytial virus (RSV) was found to
      be 1 (0.9%) in ILI and ARI. Viral co-infections were 16 (14.4%) in ILI and 4
      (4.37%) in ARI where pandemic influenza A H1N1 and influenza type B were major
      contributors. In bacterial infections, Streptococcus pneumoniae with 11 (10.9%)
      cases were predominant in both the groups. Bacterial co-infection accounted for
      only 1 (1.09%) case in both the groups but the most significant finding was the
      viral-bacterial co-infection in which Haemophilus influenzae was the major co
      infecting bacteria with the influenza viruses with 4 (4.36%) cases as compared
      with Streptotoccus pneumoniae. CONCLUSION: This data indicate the need to
      undertake continued surveillance that will help to better define the circulation
      of respiratory viruses along with the bacterial infections.

PMID- 25560002
TI  - Device-associated infections at a level-1 trauma centre of a developing nation:
      impact of automated surveillance, training and feedbacks.
AB  - PURPOSE: Device-associated infections constitute the majority of health care
      associated infections (HAIs) in ICUs. Trauma patients are predisposed to acquire
      such infections due to various trauma-related factors. The prevalence of HAIs is
      underreported from developing nations due to a lack of systematic surveillance.
      This study reports the impact of an intensive surveillance on the rates and
      outcome of device-associated infections in trauma patients from a developing
      country and compares the rates with a previous pilot observation. MATERIALS AND
      METHODS: The study was conducted at a level-1 trauma centre of India.
      Surveillance for ventilator-associated pneumonia (VAP), central line-associated
      blood stream infections (CLA-BSIs) and catheter-associated urinary tract
      infections (CA-UTIs) was done based on centre for disease control-National
      Healthcare Safety Network (CDC-NHSN) definitions. The impact of an intensive
      surveillance, education and awareness drive on the rates of infections over the
      study period, and compliance to preventive bundles and hand hygiene was assessed.
      RESULTS: A total of 15,462 ventilator days, 12,207 central line days and 17,740
      urinary catheter days were recorded in the study population. The overall rates of
      VAP, CLA-BSI and CA-UTI were respectively 17, 7.2 and 15.5/1000 device days.
      There was a significant correlation between device days and the propensity to
      develop infections. Infections were the cause of death in 36.6% of fatal trauma
      cases. A significantly higher rate of VAP, CLA-BSI and CA-UTIs was noted in fatal
      cases. The compliance to ventilator bundle, central line bundle, bladder bundle
      and hand hygiene were 74.5%, 86%, 79.3% and 64.6%, respectively. A high rate of
      multi-drug-resistance was observed in all pathogens. A gross reduction in the
      rates of all infections was observed over time during the study due to
      implementation of a stringent surveillance system, feedbacks and education. The
      compliance to hand hygiene and preventive bundles also increased over time.
      CONCLUSION: The automated surveillance was easy and useful for data entry and
      analysis. Surveillance had a significant impact on reduction of HAIs and
      mortality in trauma patients.

PMID- 25560003
TI  - Usefulness of a centrifuged buffy coat smear examination for diagnosis of
      malaria.
AB  - PURPOSE: Malaria continues to be a global public health challenge. Microscopic
      examination of peripheral blood smear (PBS) is the standard method for malaria
      diagnosis, which is easily available and has low cost but its reliability is
      questionable at low level of parasitaemia. The present study was undertaken to
      assess the usefulness of a modified centrifuged buffy coat smear (CBCS) technique
      for diagnosis of malaria and to compare it with conventional PBS examination and
      antigen detection test. MATERIALS AND METHODS: The study was carried out over a 6
      month period from July to December 2011. Blood samples (2-3 ml per patient)
      collected in EDTAvials from patients with a clinical suspicion of malaria were
      subjected to all three tests, that is PBS, CBCS and antigen test and results were
      compared with antigen test as the gold standard. RESULT: Of 1655 samples
      received, 394 (23.8%) samples were positive for infection with malaria parasites.
      All the three tests detected malaria infection equally in 279 samples, and gave
      varied results in the remaining 115 samples. Addition of centrifugation (i.e.
      CBCS) to the conventional method of PBS enabled detection of 80 more cases of
      plasmodia infection, especially (43, 53.7%) at low levels of parasitaemia (<200
      parasites/MUl). While both PBS and CBCS had excellent specificity (99.7% and
      99.2%, respectively), PBS examination had low sensitivity (72.9%) in detecting
      malaria parasites in comparison to CBCS. The sensitivity of CBCS in detecting
      malaria parasites was 91.9%. CONCLUSION: The development of easy, rapid and
      accurate tests for the reliable detection of plasmodia infection is highly
      desirable. The CBCS technique fulfils most of these criteria and may be adopted
      for rapid and reliable diagnosis of malaria in resource-limited settings.

PMID- 25560004
TI  - Seroprevalence of Scrub typhus at a tertiary care hospital in Andhra Pradesh.
AB  - INTRODUCTION: Scrub typhus is a rickettsial infection which is caused by Orientia
      tsutsugamushi and transmitted by the bite of the chigger of a mite. Delay in
      diagnosis can be fatal otherwise the treatment is simple, doxycycline being the
      drug of choice. Indirect immunoflurescence is considered gold standard but it is
      not used in India as it is costly and also not available. There is need for
      rapid, economic and simple test for the diagnosis of scrub typhus. This study was
      taken up to study the seroprevalence of scrub typhus in Andhra Pradesh and to
      compare two commonly used serological methods; rapid test and IgM ELISA.
      MATERIALS AND METHODS: This is a prospective study in which 100 serum samples
      from clinically suspected cases collected over a period of 3 months were
      processed for the detection of IgM antibodies for scrub typhus by ELISA and Rapid
      test. Samples were also tested for leptospirosis and dengue fever which the other
      common causes of fever prevalent in this region. RESULTS: Total number of samples
      processed was 100 of which 52 were males and 48 females. Among the hundred
      samples 39 were seropositive. Positivity was higher in the age group of patients
      between 16 and 30 yrs of age. There was 97% correlation between ELISA and rapid
      method. Of the 100 samples only three samples positive by ELISA were negative by
      rapid method. Fever was the most common manifestation and there was no eschar and
      no mortality reported. CONCLUSION: Scrub typhus should be included in the
      differential diagnosis of fever of unknown origin along with dengue, malaria and
      leptospirosis which are the other common endemic infections in this part of the
      country.

PMID- 25560005
TI  - Comparison of multiplex RT-PCR with virus isolation for detection, typing and sub
      typing of influenza virus from influenza-like illness cases.
AB  - PURPOSE: Influenza epidemics and periodic pandemics occur worldwide resulting in
      significant mortality, morbidity and economic loss. There is need for a
      sensitive, rapid and cost-effective assay to detect, type and sub-type influenza
      viruses, as cell culture has a long turnaround time. MATERIALS AND METHODS:
      Nasopharyngeal swabs were collected from patients presenting with influenza-like
      illness (ILI) at AIIMS OPD and Primary Health Centre Ballabhgarh (Haryana). From
      June 2007 to January 2009 and then from September to November 2009, of 1567
      specimens collected, 544 were randomly selected and were tested by virus culture
      using Madin-Darby Canine Kidney (MDCK) cells and by reverse transcription
      polymerase chain reaction (RT-PCR) for influenza A using primers for matrix gene
      and for influenza B using non-structural gene (NS) primers. All influenza A
      positives were sub-typed using primers for HA and NA genes of A/H1, A/H3. A
      separate multiplex RT-PCR having primers from matrix and HA genes of pandemic A
      (H1N1) pdm09 viruses was carried out on samples collected after September 2009.
      RESULTS: Of the 544 samples, 136 (25%) were positive for influenza by RT-PCR.
      Further typing analysis revealed 86 (63.2%) were typed as influenza A and 47
      (34.5%) as influenza B viruses and 3 (2%) samples showed dual infection with
      influenza A and B. Of the 86 influenza A positive samples 48 (55.8%) were
      identified as seasonal influenza A/H1N1, 22 (25.6%) as A (H1N1) pdm09 and 16
      (18.6%) as A/H3N2. Comparison of influenza positivity using virus culture
      revealed that only 97/136 (71.3%) were influenza positive. Sensitivity of viral
      detection was lowest for seasonal A/H1 (26/48; 54%), followed by H3N2 (11/16;
      68.7%) and influenza B (38/47; 80.8%); all influenza A/H1N1pdm09 viruses were
      detected by both methods. CONCLUSION: RT-PCR is a sensitive, low cost and rapid
      screening test for diagnosing influenza infection during epidemics and pandemics.
      mRT-PCR increased the detection rates for influenza by 28.6% as compared with
      virus isolation and thus is a useful assay in both diagnostic and epidemiological
      settings in resource poor countries.

PMID- 25560006
TI  - Current scenario of opportunistic and co-infections in HIV-infected individuals
      at a tertiary care hospital in Mumbai, India.
AB  - PURPOSE: An update on opportunistic infections/co-infections (OIs/CIs) is
      essential to understand the success of highly active antiretroviral therapy
      offered by the government agencies in reducing AIDS-related OIs/CIs. Hence, the
      present study aimed to evaluate the frequency of OIs/CIs in HIV-positive
      individuals at a tertiary care hospital in Mumbai. Its' association with CD4
      counts, anti-retroviral treatment and on HIV transmission was also determined.
      MATERIALS AND METHODS: An observational study was designed to evaluate different
      OIs/CIs in individuals, who tested positive for HIV infection at the ICTC/Shakti
      Clinic of Seth G.S. Medical College and KEM Hospital, Mumbai. Data analysis was
      done with the use of SPSS software (version 19.0, SPSS, Chicago, IL, USA). P
      value was considered significant if it is < 0.05. RESULTS: Heterosexual contact
      was the major route of transmission among the enrolled 185 individuals. Ninety
      (48.06%) HIV-infected individuals were with OIs/CIs. Tuberculosis (TB) was the
      most common OI (68.8%). Other CIs noted were Herpes zoster, syphilis, hepatitis C
      and B, malaria, typhoid and dengue. The median CD4 count in HIV-positive
      individuals with TB was 337 +/- 248 cells/MUl, and 67.7% of individuals with
      OIs/CIs had low CD4 counts (<400 cells/MUl). Individuals in 31-40 years of age
      group had significantly (P = 0.01) more OIs/CIs. More (53.7%) spouse/children of
      HIV-positive individuals without OIs/CIs were HIV-1 positive. Low proportions of
      individuals with or without OIs/CIs were on ART. CONCLUSION: Nearly half of HIV
      infected individuals were with OIs/CIs. Initiation of free ART programme since
      2004 possibly associated with the type and rate of OIs/CIs. Tuberculosis and
      multiple OIs/CIs were associated with low CD4 counts. Infection was high in 31-40
      years age group. Most of the spouses of individuals without OIs/CIs were HIV
      positive, indirectly indicates lack of condom use or lack of awareness of condom
      use.

PMID- 25560007
TI  - Contribution of efflux pumps in fluroquinolone resistance in multi-drug resistant
      nosocomial isolates of Pseudomanas aeruginosa from a tertiary referral hospital
      in north east India.
AB  - BACKGROUND: Pseudomonas aeruginosa is one of the leading opportunistic pathogen
      and its ability to acquire resistance against series of antimicrobial agents
      confine treatment option for nosocomial infections. Increasing resistance to
      fluroquinolone (FQ) agents has further worsened the scenario. The major mechanism
      of resistance to FQs includes mutation in FQs target genes in bacteria (DNA
      gyrase and/or topoisomerases) and overexpression of antibiotic efflux pumps.
      OBJECTIVE: We have investigated the role of efflux pump mediated FQ resistance in
      nosocomial isolates of P. aeruginosa from a tertiary referral hospital in north
      eastern part of India. MATERIALS AND METHODS: A total of 234 non-duplicate,
      consecutive clinical isolates of P. aeruginosa were obtained from a tertiary
      referral hospital of north-east India. An efflux pump inhibitor (EPI), carbonyl
      cyanide m-chlorophenylhydrazone (CCCP) based method was used for determination of
      efflux pump activity and multiplex polymerase chain reaction (PCR) was performed
      for molecular characterisation of efflux pump. Minimum inhibitory concentration
      (MIC) reduction assay was also performed for all the isolates. RESULTS AND
      CONCLUSION: A total number of 56 (23%) have shown efflux mediated FQ resistance.
      MexAB-OprM efflux system was predominant type. This is the first report of efflux
      pump mediated FQ resistance from this part of the world and the continued
      emergence of these mutants with such high MIC range from this part of the world
      demands serious awareness, diagnostic intervention, and proper therapeutic
      option.

PMID- 25560008
TI  - Clonal evolution multi-drug resistant Acinetobacter baumannii by pulsed-field gel
      electrophoresis.
AB  - BACKGROUND: Acinetobacter baumannii is usually multi-drug resistant (MDR),
      including third generation cephalosporins, amino glycosides and fluoroquinolone.
      Resistance to these antibiotics is mediated by multiple factors such as:
      lactamases, efflux pumps and other mechanisms of resistance. Pulsed-field gel
      electrophoresis (PFGE) was then used to investigate the genetic relationships
      among the MDR isolates. AIM: The aim of this study was to determine MDR isolates
      and the existence of OXAs genes among MDR isolates of A. baumannii collected from
      Kermanshah hospitals in west of Iran. MATERIALS AND METHODS: Forty-two MDR A.
      baumannii were collected from patients at Kermanshah hospitals. The isolates were
      identified by biochemical tests and API 20NE kit. The susceptibility to different
      antibiotics by disk diffusion method was determined. Polymerase chain reaction
      (PCR) was performed for detection of blaOXA-23-like , blaOXA-24-like , blaOXA-51
      like and blaOXA-58-like betalactamase genes in isolates and clonal relatedness
      was done by PFGE (with the restriction enzyme ApaI) and patterns analyzed by
      Bionumeric software. RESULTS: This study showed high resistant to ciprofloxacin,
      piperacillin, ceftazidime and also resistant to other anti-microbial agents and
      more spread blaOXA-23-like gene (93%) in MDR isolate. The PFGE method obtained
      six clones: A (10), B (9), C (5), D (4), E (11) and F (3) that clone E was
      outbreak and dominant in different wards of hospitals studied. CONCLUSION: An
      isolate from the emergency ward of these hospitals had indistinguishable isolates
      PFGE profile and similar resistance profile to isolates from intensive care unit
      (ICU), suggesting likely transmission from ICU to emergency via patient or
      hospital staff contact.

PMID- 25560009
TI  - Detection of phospholipase activity of Candida albicans and non albicans isolated
      from women of reproductive age with vulvovaginal candidiasis in rural area.
AB  - BACKGROUND: Vulvovaginal candidiasis (VVC) is most common accounting for 17 to
      39% of symptomatic women. Both Candida albicans and non albicans Candida species
      are involved in VVC. Amongst various virulence factors proposed for Candida,
      extracellular phospholipases is one of the virulence factor implicated in its
      pathogenicity. With this background the present study was carried out to find the
      prevalence of different Candida species and to detect phospholipase producing
      strains isolated from symptomatic women with VVC. MATERIALS AND METHODS: At least
      two vaginal swabs from 156 women of reproductive age with abnormal vaginal
      discharge were collected. Direct microscopy and Gram's stained smear examined for
      presence of budding yeast and pseudo mycelia followed by isolation and
      identification of Candida species. Extracellular phospholipase activity was
      studied by inoculating all isolates on Sabouraud's dextrose egg yolk agar (SDA)
      medium. RESULTS: Of the 156 women with curdy white discharge alone or in
      combination with other signs, 59 (37.82%) women showed laboratory evidence of
      VVC. A total of 31 (52.54%) women had curdy white discharge followed by 12
      (20.33%) with other signs and symptoms. C. albicans (62.59%) and non albicans
      Candida (37.28%) in a ratio of 1.68:1 were isolated. Of the 37 strains of C.
      albians 30 (81.08%) showed the enzyme activity. Seventeen (56.66%) strains showed
      higher Pz value of < 0.70 (++++). CONCLUSION: Although there may be typical
      clinical presentation of Candidiasis. all the patients did not show laboratory
      evidence of infection. Pregnancy was found to be major risk factor for
      development of VVC. C. albicans was prevalent species but non albicans species
      were also frequently isolated. Extracellular phospholipase activity was seen in
      C. albicans and not in non albicans Candida isolates.

PMID- 25560010
TI  - Correlation between two chemiluminescence based assays for quantification of
      hepatitis B surface antigen in patients with chronic hepatitis B infection.
AB  - PURPOSE: Hepatitis B surface Antigen (HBsAg) is the hallmark in diagnosing
      hepatitis B virus (HBV) infection. In India many commercial assays are available
      for detection of HBsAg but very few can measure it quantitatively. The present
      study presents the comparative evaluation of two methods and their correlation
      with serum HBsAg in chronic hepatitis B (CHB) patients. MATERIALS AND METHODS:
      Consecutive patients of CHB were included and there HBsAg levels were measured by
      two methods: (i) Elecsys, Roche Diagnostics, a qualitative assay and (ii)
      Architect, Abbott Diagnostics, a quantitative assay. The HBV DNA was measured by
      real-time polymerase chain reaction (qPCR). RESULTS: Total of 136 patients were
      included in the study and there was a significant overall correlation between
      both the assays (correlation coefficient [r] = 0.83; P < 0.001). Assays
      correlated well with each other across all subgroups of CHB: treatment
      naomicronve (r = 0.73; P < 0.001, n = 32), on treatment (r = 0.56; P < 0.05, n =
      104), hepatitis Be (HBe) antigen positive (r = 0.67; P < 0.001, n = 62) and anti
      HBe positive (r = 0.61; P < 0.05, n = 74) group. On correlation with serum HBV
      DNA, Architect assay demonstrated good correlation (r = 0.73; P < 0.001, n = 136)
      as compared to the Elecsys assay (r = 0.27; P = 0.068, n = 136). Architect HBsAg
      QT assay (A1) also correlated well with HBV DNA in the treatment naomicronve
      group (r = 0.69; P < 0.001, n = 32). CONCLUSIONS: Our study hence proved that
      both the assays are comparable and a simple qualitative assay with in-house
      modification can be used easily for quatitation of HBsAg in clinical samples.

PMID- 25560011
TI  - Anti-biofilm efficacy of silver nanoparticles against MRSA and MRSE isolated from
      wounds in a tertiary care hospital.
AB  - PURPOSE: Different approaches have been used for preventing biofilm-related
      infections in health care settings. Many of these methods have their own de
      merits, which include chemical-based complications; emergent antibiotic resistant
      strains, etc. The formation of biofilm is the hallmark characteristic of
      Staphylococcus aureus and S. epidermidis infection, which consists of multiple
      layers of bacteria encased within an exopolysachharide glycocalyx. Nanotechnology
      may provide the answer to penetrate such biofilms and reduce biofilm formation.
      Therefore, the aim of present study was to demonstrate the biofilm formation by
      methicillin resistance S. aureus (MRSA) and methicillin resistance S. epidermidis
      (MRSE) isolated from wounds by direct visualisation applying tissue culture
      plate, tube and Congo Red Agar methods. MATERIALS AND METHODS: The anti-biofilm
      activity of AgNPs was investigated by Congo Red, scanning electron microscopy
      (SEM) and confocal laser scanning microscopy (CLSM) techniques. RESULTS: The
      minimum inhibitory concentration (MIC) was found to be in the range of 11.25-45
      MUg/ml. The AgNPs coated surfaces effectively restricted biofilm formation of the
      tested bacteria. Double fluorescent staining (propidium iodide staining to detect
      bacterial cells and fluorescein isothiocyanate concanavalin A (Con A-FITC)
      staining to detect the exopolysachharides matrix) technique using CLSM provides
      the visual evidence that AgNPs arrested the bacterial growth and prevent the
      glycocalyx formation. In our study, we could demonstrate the complete anti
      biofilm activity AgNPs at a concentration as low as 50 MUg/ml. CONCLUSIONS: Our
      findings suggested that AgNPs can be exploited towards the development of
      potential anti-bacterial coatings for various biomedical and environmental
      applications. In the near future, the AgNPs may play major role in the coating of
      medical devices and treatment of infections caused due to highly antibiotic
      resistant biofilm.

PMID- 25560012
TI  - Novel synthetic anti-fungal tripeptide effective against Candida krusei.
AB  - INTRODUCTION: Candida species are the major fungal pathogens of humans. Among
      them, Candida krusei have emerged as a notable pathogen with a spectrum of
      clinical manifestations and is known to develop resistance against azoles mainly
      fluconazole. Anti-microbial peptides play important roles in the early mucosal
      defence against infection and are potent anti-fungal agents since they fight
      against fungal infection as well as have ability to regulate host immune defence
      system. The aim of the study was to synthesize a small anti fungal peptide.
      MATERIALS AND METHODS: The series of tripeptides were synthesized and screened
      for antifungal activity against Candida strains according to CLSI guidelines.
      Toxicity effect of peptide was tested with human erythrocytes. The mode of action
      of peptide on fungus was resolved by scanning electron microscopy (SEM) studies
      Results: The tripeptide FAR showed a prominent anti fungal activity among the
      series. The minimum inhibitory concentration and minimum fungicidal concentration
      of tripeptide FAR was found to be 171.25 MUg/ml and 685 MUg/ml, respectively
      against Candida krusei . The therapeutic index was 2.9. The haemolytic experiment
      revealed that this peptide is non-toxic to human cells. The SEM studies showed
      disruption of cell wall and bleb-like surface changes and irregular cell surface.
      CONCLUSION: The peptide showed a significant antifungal activity against C.
      krusei. Thus, it can set a platform for the design of new effective therapeutic
      agents against C. krusei.

PMID- 25560013
TI  - Outbreak of Burkholderia cepacia complex bacteremia in a chemotherapy day care
      unit due to intrinsic contamination of an antiemetic drug.
AB  - BACKGROUND: In the end of 2009, a large number of patients with cancer undergoing
      chemotherapy at the day care unit of a private hospital in Mumbai, India
      developed Burkholderia cepacia complex (BCC) blood stream infection (BSI).
      OBJECTIVE: The objectives were to identify the source of the outbreak and
      terminate the outbreak as rapidly as possible. MATERIALS AND METHODS: All
      infection control protocols and processes were reviewed. Intensive training was
      started for all nursing staff involved in patient care. Cultures were sent from
      the environment (surfaces, water, air), intravenous fluids, disinfectants and
      antiseptics and opened/unopened medication. RESULTS: A total of 13 patients with
      cancer with tunneled catheters were affected with BCC BSI. The isolates were of
      similar antimicrobial sensitivity. No significant breach of infection control
      protocols could be identified. Cultures from the prepared intravenous medication
      bags grew BCC. Subsequently, culture from unused vials of the antiemetic
      granisetron grew BCC, whereas those from the unopened IV fluid bag and
      chemotherapy medication were negative. On review, it was discovered that the
      outbreak started when a new brand of granisetron was introduced. The result was
      communicated to the manufacturer and the brand was withdrawn. There were no
      further cases. CONCLUSIONS: This outbreak was thus linked to intrinsic
      contamination of medication vials. We acknowledge a delay in identifying the
      source as we were concentrating more on human errors in medication preparation
      and less on intrinsic contamination. We recommend that in an event of an
      outbreak, unopened vials be cultured at the outset.

PMID- 25560014
TI  - Fungal rhinosinusitis: a clinicomycological perspective.
AB  - PURPOSE: Chronic rhinosinusitis (CRS) is a widely prevalent condition globally as
      well as in India. The spectrum of fungal involvement in CRS runs from benign
      colonisation to potentially life-threatening invasive disease. Successful
      treatment of such mycotic infections largely depends on the accurate
      identification of the pathogen, early and appropriate intervention by surgical
      clearance, supported with antifungal medication as per standard regimen. Thus,
      this study was undertaken to determine the prevalence of fungal rhinosinusitis
      (FRS), and to analyse its clinicomycological profile. MATERIALS AND METHODS:
      Fifty-two patients with clinical suspicion of CRS attending a tertiary care
      hospital during a one-year period were included in this retrospective analysis.
      The sinonasal specimens were subjected to microscopy by KOH mount and fungal
      culture as per standard mycological technique. Tissue specimens were also
      subjected to histopathological examination. RESULTS: Male to female ratio was
      1.25:1; age varied from 14 years to 62 years with majority of patients (37%)
      belonging to age group 21-40 years. The prevalence of FRS was 44%, and 74% of it
      was caused by Aspergillus sp. Aspergillus flavus (A. flavus) (52%) was the most
      prevalent fungus isolated. Allergic fungal rhinosinusitis (AFRS) was the most
      common presentation (79%). CONCLUSION: FRS is a continuous spectrum of disease
      varying in presentation, treatment and long-term sequelae. Correct identification
      of the fungus remains essential for appropriate treatment.

PMID- 25560015
TI  - Hand hygiene in reducing transient flora on the hands of healthcare workers: an
      educational intervention.
AB  - AIM: Hand hygiene has now been recognised as one of the most effective
      intervention to control the transmission of infections in a hospital and
      education is an important tool to ensure its implementation. In order to convince
      the users and as a part of education, it is important to generate evidence on the
      role of hand hygiene in reducing the bacterial flora on their hands. The present
      study was undertaken in a tertiary care hospital to demonstrate the presence of
      bacterial flora on the hands of healthcare workers (HCW) in different categories,
      to teach them proper hand hygiene technique using alcohol-based hand rub and
      determine the outcome for reduction of bacteria. MATERIALS AND METHODS: A total
      sample size of 60 subjects including resident doctors, medical students, nurses
      and hospital attendants were included in the study after obtaining informed
      consent. Each person was educated on the technique of hand hygiene with alcohol
      based hand rub and hand impressions were cultured before and after hand hygiene.
      All the subjects were also given a questionnaire to assess their perception on
      hand hygiene. The WHO posters on proper hand hygiene were displayed in the
      appropriate areas of the hospital in addition, as an educational tool. RESULTS:
      Majority (42 out of 60) of the HCWs had bacterial count up to 100 colonies or
      more on both hands before the application of hand rub while working in the
      hospital. After use of alcohol hand rub with a proper hand hygiene technique, it
      was found that the percentage reduction was 95-99% among doctors and nurses, 70%
      among hospital attendants and 50% among sanitary attendants. Staphylococcus
      aureus was present on the hands of eight persons of which three were methicillin
      resistant Staphylococcus aureus. CONCLUSIONS: The study demonstrates that
      transient bacteria are present on the hands of HCWs but majority could be removed
      by proper hand hygiene, which needs continuous education to be effective. It also
      shows that active education by demonstrating the proper hand hygiene technique
      and direct observation of the practices, though demanding, are ideal to
      understand the attitudes and practices of HCWs and helps in planning
      implementation strategies.

PMID- 25560016
TI  - Biomedical waste management: study on the awareness and practice among healthcare
      workers in a tertiary teaching hospital.
AB  - Bio-medical waste has a higher potential of infection and injury to the
      healthcare worker, patient and the surrounding community. Awareness programmes on
      their proper handling and management to healthcare workers can prevent the spread
      of infectious diseases and epidemics. This study was conducted in a tertiary care
      hospital to assess the impact of training, audits and education/implementations
      from 2009 to 2012 on awareness and practice of biomedical waste segregation. Our
      study reveals focused training, strict supervision, daily surveillance, audits
      inspections, involvement of hospital administrators and regular appraisals are
      essential to optimise the segregation of biomedical waste. 

PMID- 25560017
TI  - A preliminary study of recombinant human interferon-alpha-2a activity against
      rabies virus in murine model.
AB  - Rabies remains an important public health problem in the world due to
      uncontrolled enzootic rabies. Although rabies associated fatalities may be
      prevented with timely immunoprophylaxis, but till date a therapeutic molecule has
      remained elusive. We investigated the role of rhuIFN alpha-2a in murine model
      challenged with rabies virus. Titre of 10(4.25) LD50/0.03 ml of 10% w/v RV CVS
      stock suspension were obtained. Based on 1LD50 titre, challenge dose of 50 LD 50
      was administered along with rhuIFN alpha-2a with pre-exposure (primed) and post
      exposure with the rabies virus. Both showed increased survival time as compared
      with the virus controls. These findings suggest that the rhuIFN alpha-2a might
      have some anti-viral activity, which can be used for the treatment of rabies
      infection. Further research on the efficacy of interferon along with anti-viral
      drugs for the treatment will be helpful in designing combination therapy against
      the disease.

PMID- 25560018
TI  - Phenotyping of Salmonella serotypes isolated from natural sources of water in
      rural areas of East Sikkim.
AB  - The objective of the study was to conduct bacteriological analysis of water with
      special reference to Salmonella spp from natural sources of rural habitations of
      East Sikkim. A total of 28 Salmonella serovars isolated were biotyped, phage
      typed and tested for their anti-microbial susceptibility. All the isolates of
      Salmonella enterica serovar Typhi belonged to Biotype I. Four isolates of S.
      typhi belonged to phage type A. All S. paratyphi A isolates belong to phage 2.
      All the isolates were sensitive to chloramphenicol, cefixime and amikacin.
      Untreated natural water sources are unsafe for human consumption. 

PMID- 25560019
TI  - YnfA , a SMR family efflux pump is abundant in Escherichia coli isolates from
      urinary infection.
AB  - A quantitative study was undertaken to determine the expression level of
      different efflux pumps in multi-drug-resistant (MDR) Escherichia coli isolates
      from urinary infection. We have determined the presence of different efflux pumps
      and measured the expression level of tolC, mdfA, norE and ynfA genes among 48
      isolates by quantitative real-time PCR. The expression level of tolC and ynfA was
      constantly high and observed among 75-80% of isolates, whereas mdfA and norE were
      expressed occasionally. Our findings suggest that ynfA, a new SMR efflux pump
      gene family member increases the antibiotics' resistance in E. coli. 

PMID- 25560020
TI  - Emergence of influenza A (H1N1) PDM09 in the remote Islands of India--a molecular
      approach.
AB  - BACKGROUND: A disease outbreak of A (H1N1) PDM09 was reported in Andaman and
      Nicobar islands in 2009 with an attack rate of 33.5% among settler population and
      26.3% among the aboriginal Nicobarese tribe. During the ongoing outbreak of A
      (H1N1) PDM09 disease in different parts of the world, a subject working in Dubai
      city of Saudi Arabia, came to Port Blair, following which the pandemic triggered
      for the first time in these Islands. MATERIALS AND METHODS: During the period
      August 2009 to January 2011, 30 confirmed cases of Influenza A (H1N1) PDM09 virus
      infection was detected. To understand the genetic relationship, the NA gene
      sequences of the viruses were phylogenetically analysed together along with the
      virus sequence isolated from other parts of the world. RESULT: Formation of
      multiple clusters were observed, with the sequences of Andaman Islands, mainland
      India, Mexico, Saudi Arabia and few other counties clustering together. The
      sequence analysis data revealed that there was no specific mutation conferring
      resistance to oseltamivir among the Andaman A (H1N1) PDM09 virus isolates. The
      result of phylogenetic analysis have also revealed that the A (H1N1) PDM09 virus
      might have spread in these remote Islands of India via the subject from Saudi
      Arabia/Dubai. CONCLUSION: A (H1N1) PDM09 Influenza outbreak have highlighted the
      need to strengthen the region-specific pandemic preparedness plans and
      surveillance strategies.

PMID- 25560021
TI  - GenoType  MTBDR assay for detection of rifampicin and isoniazid resistance.

PMID- 25560022
TI  - Profile of fatal Streptococcal bacteraemia at a tertiary care Indian hospital.
AB  - Streptococcus pyogenes causes mild to acutely life-threatening diseases. Herein,
      we report our experience with five cases of fatal bacteraemia due to various
      groups of Streptococci, three of them due to Group G Streptococcus and one case
      each due to Group A Streptococcus and Group F Streptococcus. The peculiarity of
      all these cases was the rapidity of deaths occurring in these patients despite
      all the strains being sensitive to Penicillin. Hence, timely intervention in all
      suspected cases is strongly advocated. All isolates of beta-haemolytic
      Streptococci should be identified up till the species level and antimicrobial
      susceptibility be performed so that proper and early management can be done. 

PMID- 25560023
TI  - Diagnosis of primary hydatid cyst of thigh by fine needle aspiration cytology.
AB  - Hydatidosis is a parasitic infestation caused by larval form of the tapeworm,
      Echinococcus granulosus. Primary hydatid cyst in the skeletal muscles and
      subcutaneous tissue of thigh without involving thoracic and abdominal organs is
      an exceptional entity, even in countries where the Echinococcus infestation is
      endemic. We report an unusual case of primary hydatid cyst of thigh in proximity
      to skeletal muscles. This case illustrates that echinococcal disease should be
      considered in the differential diagnosis of every subcutaneous cystic mass. This
      case is presented here for its rarity. 

PMID- 25560024
TI  - Eosinophilic meningitis: a case series and review of literature of
      Angiostrongylus cantonensis and Gnathostoma spinigerum.
AB  - Eosinophilic meningitis is defined as the presence of >10 eosinophils/MUL in
      cerebrospinal fluid (CSF) or at least 10% eosinophils in the total CSF leukocyte
      count. Eosinophilic meningitis has been reported in two case series and two case
      reports in India till date and has not been reported in children below 15 years
      of age. We present two children with eosinophilic meningitis with peripheral
      eosinophilia and the proposed etiologic agents based on the clinical setting and
      their response to antihelminthic agents. 

PMID- 25560025
TI  - Hemophilus influenzae meningitis and septicaemia in a 14-month-old child after
      primary immunisation.
AB  - We report a 14-month-male child, who developed Hemophilus influenzae meningitis
      after three primary doses of the vaccine. The child presented with fever and
      seizures. H. influenzae was isolated from both cerebrospinal fluid (CSF) and
      blood. The child also had features of septicaemia. Procalcitonin (104 ng/ml) and
      C-reactive protein (CRP--42.6 mg/dl) were high. Appropriate antibiotics were
      given. The child made an uneventful recovery. This case highlights vaccine
      failure, especially after primary immunisation alone.

PMID- 25560026
TI  - Disseminated penicilliosis marneffei in immunocompetent patients: a report of two
      cases.
AB  - Disseminated penicilliosis marneffei is rarely seen in immunocompetent persons.
      We report here two cases of disseminated penicilliosis marneffei in
      immunocompetent hosts. Penicillium marneffei disseminated to the brain in one
      patient and to the bone marrow in the other patient. Both patients received
      amphotericin B liposome. The cases illustrate the importance of considering
      penicilliosis marneffei as causes of systemic infections in immunocompetent
      patients. 

PMID- 25560027
TI  - Cutaneous fungal infection in a renal transplantation patient due to a rare
      fungus belonging to order Pleosporales.
AB  - Fungal infections are being increasingly reported from immuno-compromised as well
      as immuno-competent patients. Transplant patients are on long term
      immunosuppressive therapy which makes them highly vulnerable to opportunistic
      fungal infections .These infections can be cutaneous or systemic. Several fungi
      have been reported to be the culprits such as Candida spp., Aspergillus spp., C.
      neoformans, P. carinii, and zygomycetes group of fungi. Cutaneous infections are
      most commonly caused by Pityriasis (tinea) versicolor, dermatophytes, and candida
      sp but these days the demtiaceous fungi are becoming more frequently reported
      .Here we report a case of post renal transplant cutaneous infection caused by
      dematiaceous fungus belonging to the order Pleosporales. 

PMID- 25560028
TI  - Facial lupus vulgaris of bilateral periorbital skin and conjunctiva: a case
      report and brief review.
AB  - A 22-year-old male presented to the Dermatology Department with bilateral plaque
      lesions distributed symmetrically over malar area, bridge of nose and upper
      eyelids progressing over 1 year 3 months. Lesion remained unhealed after
      antibiotic treatment. Microscopy and culture for fungal and mycobacterial
      infections were negative. The Mantoux test showed an exaggerated response and PCR
      was positive for Mycobacterium tuberculosis complex. Patient was treated
      successfully with anti-tubercular therapy. 

PMID- 25560029
TI  - Shewanella algae in acute gastroenteritis.
AB  - Shewanella algae is an emerging bacteria rarely implicated as a human pathogen.
      Previously reported cases of S. algae have mainly been associated with direct
      contact with seawater. Here we report the isolation of S. algae as the sole
      etiological agent from a patient suffering from acute gastroenteritis with bloody
      diarrhoea. The bacterium was identified by automated identification system and
      16S rRNA gene sequence analysis. Our report highlights the importance of looking
      for the relatively rare aetiological agents in clinical samples that does not
      yield common pathogens. It also underscores the usefulness of automated systems
      in identification of rare pathogens. 

PMID- 25560030
TI  - New intensive care unit and bacterial epidemiology.

PMID- 25560031
TI  - Hygiene practices and sexual activity associated with urinary tract infection in
      rural pregnant women of Nagpur, India.

PMID- 25560032
TI  - Diagnostic dilemma in hookworm infection: an unusual case report.

PMID- 25560034
TI  - Seroprevalence of coinfections among blood donors in tertiary health care centre
      of Jammu region.

PMID- 25560033
TI  - A preliminary study screening cephalosporin-resistant Enterobacteriaceae for
      blaCTX-M and blaampC isolated from Kumaun region, India.

PMID- 25560035
TI  - Evaluation of new chromogenic media for identification of uropathogens from
      complicated urinary tract infections in a tertiary healthcare setting.

PMID- 25560037
TI  - Detection of various types of resistance patterns and their correlation with
      minimum inhibitory concentrations against clindamycin among methicillin resistant
      S. aureus isolates.

PMID- 25560036
TI  - 16S rRNA PCR for the diagnosis of culture-negative Bartonella quintana
      endocarditis: the importance of sample type.

PMID- 25560038
TI  - Four year data from an ICTC of a tertiary care hospital in Jaipur, Rajasthan.

PMID- 25560039
TI  - Risk factors and genotypes of HCV infected patients attending tertiary care
      hospital in North India.

PMID- 25560040
TI  - Carriage of quinolone resistance in faecal coliforms among healthy individuals: a
      study from northeast India.

PMID- 25560041
TI  - CTX-M and PER-1 group extended spectrum beta-lactamases-producing Pseudomonas
      aeruginosa from the patients of lower respiratory tract infection.

PMID- 25560042
TI  - Cutaneous TB-presenting as recurrent non-healing sinuses.

PMID- 25560043
TI  - Dual infection of measles and rubella in Chitradurga district, Karnataka, India.

PMID- 25560044
TI  - Difference in static and dynamic stability between flexible flatfeet and neutral
      feet.
AB  - Different postural stability may be a contributor to secondary injuries in
      individuals with flexible flatfeet (FF) compared to those with neutral feet (NF).
      However, the differences between static and dynamic stability of FF and NF have
      not been examined. This study compared the static and dynamic stability of
      subjects with FF and NF and investigated the relationship between static and
      dynamic stability. Twenty-eight subjects (14 each in the FF and NF groups)
      performed three tasks (single leg standing with eyes open, with eyes closed, and
      the Y balance test). We quantified the center of pressure (COP) speed and Y
      balance test score (Y score) within the tasks. COP speed was significantly
      greater in the FF group than in the NF group under both conditions (eyes open and
      closed) and directions (anteroposterior and mediolateral). Y scores did not
      differ significantly between the two groups. No significant relationship was
      observed between the COP speed and Y score in either group. These results show
      that individuals with FF have different static stabilities, but not dynamic
      stabilities, compared with those with NF. This might indicate the absence of a
      relationship between static and dynamic stabilities.

PMID- 25560045
TI  - Preparation and upconversion emission modification of crystalline colloidal
      arrays and rare earth fluoride microcrystal composites.
AB  - In this paper, highly ordered crystalline colloidal arrays containing rare earth
      fluoride microcrystals were fabricated. The upconversion emission property of
      rare earth fluoride microcrystals in crystalline colloidal arrays was studied and
      modified. A significant suppression and enhancement of the upconversion emission
      from the rare earth fluorides can be observed in the regions of the photonic band
      gap and its band edge, respectively. The suppression or enhancement factor was
      shown to be related to the ordered degree of the crystalline colloidal arrays and
      is critical in the preparation of upconversion displays and low-threshold lasers.

PMID- 25560047
TI  - Microwave and quantum-chemical study of conformational properties and
      intramolecular hydrogen bonding of 2-hydroxy-3-butynenitrile (HC=CCH(OH)C=N).
AB  - The microwave spectra of 2-hydroxy-3-butynenitrile, HC=CCH(OH)C=N, and a
      deuterated species, HC=CCH(OD)C=N, have been investigated in the 38-120 GHz
      spectral region. Three rotameric forms, each stabilized by intramolecular
      hydrogen bonds, are possible for this compound. The hydrogen atom of the hydroxyl
      group is hydrogen-bonded to the pi electrons of the alkynyl group in one of these
      conformers, to the pi electrons of the cyano group in the second rotamer, and to
      both of these groups simultaneously in the third conformer. The microwave spectra
      of the parent and deuterated species of last-mentioned form have been assigned,
      and accurate values of the rotational and quartic centrifugal distortion
      constants of these species have been determined. The spectra of two vibrational
      excited states of this conformer have also been assigned, and their frequencies
      have been determined by relative intensity measurements. Quantum-chemical
      calculations at the MP2/cc-pVTZ and CCSD/cc-pVQZ levels were performed to assist
      the microwave work. The theoretical predictions were generally found to be in
      good agreement with observations. 

PMID- 25560048
TI  - Deep brain stimulation for Parkinson disease: the 2014 Lasker-DeBakey Clinical
      Medical Research Award.

PMID- 25560050
TI  - Letter to the Editor: "Can early plasma elimination rate be used to quantify
      renal clearance of macromolecules?".

PMID- 25560046
TI  - Transdermal patches: history, development and pharmacology.
AB  - Transdermal patches are now widely used as cosmetic, topical and transdermal
      delivery systems. These patches represent a key outcome from the growth in skin
      science, technology and expertise developed through trial and error, clinical
      observation and evidence-based studies that date back to the first existing human
      records. This review begins with the earliest topical therapies and traces
      topical delivery to the present-day transdermal patches, describing along the way
      the initial trials, devices and drug delivery systems that underpin current
      transdermal patches and their actives. This is followed by consideration of the
      evolution in the various patch designs and their limitations as well as
      requirements for actives to be used for transdermal delivery. The properties of
      and issues associated with the use of currently marketed products, such as
      variability, safety and regulatory aspects, are then described. The review
      concludes by examining future prospects for transdermal patches and drug delivery
      systems, such as the combination of active delivery systems with patches,
      minimally invasive microneedle patches and cutaneous solutions, including metered
      dose systems. 

PMID- 25560049
TI  - Effects of an H3R antagonist on the animal model of autism induced by prenatal
      exposure to valproic acid.
AB  - Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders
      primarily characterized by impaired social interaction and communication, and by
      restricted repetitive behaviors and interests. Ligands of histamine receptor 3
      (H3R) are considered potential therapeutic agents for the treatment of different
      brain disorders and cognitive impairments. Considering this, the aim of the
      present study is to evaluate the actions of ciproxifan (CPX), an H3R antagonist,
      on the animal model of autism induced by prenatal exposure to valproic acid
      (VPA). Swiss mice were prenatally exposed to VPA on embryonic day 11 and assessed
      for social behavior, nociceptive threshold and repetitive behavior at 50 days of
      life. The treatment with CPX (3 mg/kg) or saline was administered 30 minutes
      before each behavioral test. The VPA group presented lower sociability index
      compared to VPA animals that were treated with CPX. Compared to the Control
      group, VPA animals presented a significantly higher nociceptive threshold, and
      treatment with CPX was not able to modify this parameter. In the marble burying
      test, the number of marbles buried by VPA animals was consistent with markedly
      repetitive behavior. VPA animals that received CPX buried a reduced amount of
      marbles. In summary, we report that an acute dose of CPX is able to attenuate
      sociability deficits and stereotypies present in the VPA model of autism. Our
      findings have the potential to help the investigations of both the molecular
      underpinnings of ASD and of possible treatments to ameliorate the ASD
      symptomatology, although more research is still necessary to corroborate and
      expand this initial data. 

PMID- 25560051
TI  - Effects of terbinafine and itraconazole on the pharmacokinetics of orally
      administered tramadol.
AB  - BACKGROUND: Tramadol is widely used for acute, chronic, and neuropathic pain. Its
      primary active metabolite is O-desmethyltramadol (M1), which is mainly
      accountable for the MU-opioid receptor-related analgesic effect. Tramadol is
      metabolized to M1 mainly by cytochrome P450 (CYP)2D6 enzyme and to other
      metabolites by CYP3A4 and CYP2B6. We investigated the possible interaction of
      tramadol with the antifungal agents terbinafine (CYP2D6 inhibitor) and
      itraconazole (CYP3A4 inhibitor). METHODS: We used a randomized placebo-controlled
      crossover study design with 12 healthy subjects, of which 8 were extensive and 4
      were ultrarapid CYP2D6 metabolizers. On the pretreatment day 4 with terbinafine
      (250 mg once daily), itraconazole (200 mg once daily) or placebo, subjects were
      given tramadol 50 mg orally. Plasma concentrations of tramadol and M1 were
      determined over 48 h and some pharmacodynamic effects over 12 h. Pharmacokinetic
      variables were calculated using standard non-compartmental methods. RESULTS:
      Terbinafine increased the area under plasma concentration-time curve (AUC0
      infinity) of tramadol by 115 % and decreased the AUC0-infinity of M1 by 64 % (P <
      0.001). Terbinafine increased the peak concentration (C max) of tramadol by 53 %
      (P < 0.001) and decreased the C max of M1 by 79 % (P < 0.001). After terbinafine
      pretreatment the elimination half-life of tramadol and M1 were increased by 48
      and 50 %, respectively (P < 0.001). Terbinafine reduced subjective drug effect of
      tramadol (P < 0.001). Itraconazole had minor effects on tramadol
      pharmacokinetics. CONCLUSIONS: Terbinafine may reduce the opioid effect of
      tramadol and increase the risk of its monoaminergic adverse effects. Itraconazole
      has no meaningful interaction with tramadol in subjects who have functional
      CYP2D6 enzyme.

PMID- 25560053
TI  - To absent friends.

PMID- 25560052
TI  - Prescription and indication trends of antidepressant drugs in the Netherlands
      between 1996 and 2012: a dynamic population-based study.
AB  - PURPOSE: Antidepressant drug use increases worldwide. It is pivotal to closely
      monitor the use of antidepressants and to determine in what subpopulations the
      rise is most substantial. In a Dutch primary care database, we aimed to
      investigate the (sex- and age-specific) prevalence and incidence of
      antidepressant prescription and to monitor the indication of incident
      prescriptions over a 17-year period (1996-2012). METHODS: This study, embedded in
      the Integrated Primary Care Information database, included all patients aged 10
      years or older. Per calendar year, prevalence and incidence of antidepressant
      drug prescription were calculated by drug class (tricyclic antidepressants,
      selective serotonin reuptake inhibitors (SSRIs), and others), sex, and age. The
      indication of incident prescriptions (e.g., depression, anxiety, sleep disorders,
      and neuropathic pain) was determined based on the International Classification of
      Primary Care codes. RESULTS: In total, 1.49 million patients were included. For
      all antidepressants together, the prevalence increased over time. However,
      incident prescription of specific SSRIs decreased from 2000 onward. During the
      study period, incidence and prevalence were higher in older and female patients.
      The increase in prevalence and the decrease in incidence were more pronounced in
      females than that in males. Furthermore, antidepressants were increasingly
      prescribed for indications such as neuropathic pain and sleep disorders.
      CONCLUSIONS: In Dutch primary care, prevalent prescription of antidepressants
      continued to increase, but incident prescription of particular SSRIs decreased
      from 2000 onward. In later years, antidepressants were less frequently prescribed
      for depression-related indications in incident users.

PMID- 25560054
TI  - Metal on metal total hip arthroplasty and a large groin mass: Not always adverse
      reaction to metallic debris.
AB  - Due to their improved wear rates, Metal-on-metal bearings have been increasingly
      used in the past decade by orthopaedic surgeons carrying out total hip
      arthroplasty. However there is increasing evidence that there are significant
      complications associated with such implants. One well documented complication is
      that of metallic debris leading to pseudotumour formation, however there is less
      known about associations with other tumours within the pelvis. We present two
      cases where an intra-pelvic mass in patients with metal-on-metal implants were
      diagnosed as being of a different aetiology. This highlights the need for careful
      assessment of such patients in order to guide appropriate management. 

PMID- 25560055
TI  - Radiographic findings following irrigation of chronic perineal drain with
      hydrogen peroxide.
AB  - INTRODUCTION: Hydrogen peroxide is a widely available agent used for irrigation
      and disinfecting. With misuse, significant side effects have been noted ranging
      from nausea to abdominal cramping to portal venous gas, air embolism and death.
      PRESENTATION OF CASE: We present an 81 year old male who developed a
      rectovesicular fistula following radiation for metastatic prostate cancer. He had
      recurrent bleeding and infections and underwent a pelvic exenteration which was
      complicated by a persistent pelvic abscess requiring placement of a transperineal
      drainage catheter. After months of persistent drainage, he noted decreased output
      and irrigated the catheter with 3% hydrogen peroxide. He presented to the
      emergency room with fever, diarrhea and abdominal cramping but no rebound or
      guarding. CT depicted free air in the pre-sacral space extending into the
      retroperitoneum and diffusely throughout the peritoneum. Given his clinical exam
      and upon review of imaging, we assumed his radiographic findings were related to
      the direct instillation of hydrogen peroxide into his chronic pelvic cavity.
      DISCUSSION: Hydrogen peroxide has been used therapeutically for over 100 years.
      Hydrogen peroxide exerts direct cytotoxicity by corrosion and lipid peroxidation
      and indirectly by oxygen gas formation. When the oxygen produced exceeds the
      solubility in the blood, arterial and venous gas embolism occur. It is this
      sequelae of hydrogen peroxide that is described most frequently in the
      literature. CONCLUSION: Instillation of hydrogen peroxide into a chronic pelvic
      cavity resulted in a benign pneumoperitoneum. This effect of hydrogen peroxide is
      a significant and potentially treatment altering radiographic finding.

PMID- 25560056
TI  - Temporary hyperlactataemia during partial hepatectomy: Report of two cases.
AB  - Lactic acidosis (LA) is characterized by accumulation of lactate in the body, and
      it may detrimentally affect homeostasis. Perioperative LA is rarely seen, here we
      presented 2 cases of patients suffered with temporary hyperlactataemia during
      partial hepatectomy, intended to emphasize that prolonged hypovolemia condition
      caused by controlled low central venous pressure, and overused hepatic vascular
      occlusion technique during parenchymal resection of hepatic surgery may seriously
      impact on the internal environment of patients. And we also discussed how to well
      manage long-time hepatectomy to prevent LA from occurring and to treat it
      appropriately. 

PMID- 25560057
TI  - Surgically inverting an incidentally detected Meckel's diverticulum - Wrong
      method.
AB  - INTRODUCTION: Intusussception leading to intestinal obstruction is a known
      complication of Meckel's diverticulum. Inverting of Meckel's acts as a lead point
      for intussusception. Causes of inversion are many but surgical inversion leading
      to intusussception is extremely rare. PRESENTATION OF CASE: We hereby report a
      case of a 14 year adolescent boy operated previously for open appendicetomy
      presenting to us with intestinal obstruction who on exploration was found to have
      an surgically inverted Meckel's diverticulum acting as a lead point for ileo
      colic intusussception. DISCUSSION: To the best of our knowledge, surgically
      inverting any Meckel's diverticulum is never a treatment option even when the
      diverticulum is incidentally detected. Diverticulectomy or segmental resection is
      the procedure of choice for Meckel's diverticulum. CONCLUSION: Meckel's
      divereticulum should never be inverted surgically. Not only it is a wrong method
      but also increases the risk of complications.

PMID- 25560058
TI  - Nocardia prosthetic knee infection successfully treated by one-stage exchange:
      case report and review.
AB  - A 64-year-old man with a history of sarcoidosis on corticosteroids and
      azathioprine was admitted to our hospital with complaints of worsening left knee
      pain and swelling for the past 3 weeks. His past medical history is also
      significant for severe osteoarthritis requiring a cemented total left knee
      arthroplasty 1 year ago. Diagnostic investigation during his hospital admission
      eventually led to the diagnosis of Nocardia nova knee prosthetic joint infection
      in the setting of a disseminated nocardiosis. He was successful treated by one
      stage complete hardware exchange in conjunction with an adapted antibiotic
      therapy regimen (meropenem and doxycycline followed by ceftriaxone and
      doxycycline). Two years later, his recovery was deemed excellent. 

PMID- 25560059
TI  - Cystinosis: a new perspective.
AB  - Cystinosis is a rare, autosomal recessive inherited lysosomal storage disease. It
      is the most frequent and potentially treatable cause of the inherited renal
      Fanconi syndrome. If left untreated, renal function rapidly deteriorates towards
      end-stage renal disease by the end of the first decade of life. Due to its rarity
      and non-specific presentation, the entity is often not promptly recognized
      resulting in delayed diagnosis. Two major milestones in cystinosis management,
      cystine-depleting therapy with cysteamine and renal allograft transplantation,
      have had a considerable impact on the natural history and prognosis of cystinosis
      patients. However, due to its significant side effects and a strict 6-hourly
      dosing regimen, non-adherence to the immediate release of cysteamine bitartrate
      formulation (Cystagon(r)) is a major issue that might affect long-term outcome.
      Recently, a new twice-daily administered delayed-release enteric-coated formula
      of cysteamine bitartrate (Procysbi(TM)) has been approved by the European Medical
      Agency for the treatment of cystinosis, and has been shown to be safe and
      effective. This delayed-release cysteamine has the potential to improve
      compliance and hence prognosis, through its better dosing regimen, positive
      impact on quality of life and possibly less side-effects, and is now tested in an
      ongoing long-term clinical trial. Longer survival of patients with cystinosis
      makes transition from pediatric to adult-oriented care another challenge in
      cystinosis management and requires an extended multidisciplinary approach. 

PMID- 25560060
TI  - Comparison between classical polyarteritis nodosa and single organ vasculitis of
      medium-sized vessels: a retrospective study of 25 patients and review of the
      literature.
AB  - BACKGROUND: Polyarteritis nodosa (PAN) is a rare form of systemic vasculitis,
      characterized by necrotizing inflammation of medium-sized vessels. In clinical
      practice, the distinction is made between a limited, mostly cutaneous, form and a
      generalized form. The Chapel Hill Consensus Conference of 2012 on the
      classification of the vasculitides classifies PAN as a medium vessel vasculitis,
      whereas the limited forms fall under the heading 'single-organ vasculitis' (SOV),
      with subdivions such as 'cutaneous arteritis' (formerly called cutaneous PAN) and
      'others'. In this last category, forms of PAN limited to a single organ (e.g.
      testicle, gall bladder or appendix) should be categorized. The relation between
      classical and limited forms of PAN remains enigmatic. OBJECTIVE: To compare
      demographics, clinical characteristics and prognosis between SOV and generalized
      PAN. METHODS: Clinical files of all patients with a diagnosis of classical or
      limited PAN made in the departments of general internal medicine and dermatology
      between 1983 and 2013 in a tertiary care university hospital were reviewed.
      RESULTS: The patients of the SOV group tend to be younger, with a female
      predominance, while we observed a male predominance in the generalized PAN group.
      Relapses were more common in SOV than in classical PAN. None of the patients
      initially diagnosed with cPAN/SOV progressed to generalized disease. DISCUSSION:
      Though SOV and classical PAN share a lot of similarities, they are probably
      different disease entities, based on their different demographical, clinical and
      prognostic characteristics. The 1990 ACR-criteria for classical PAN are too broad
      since they allow patients with limited disease to be classified as classic PAN.

PMID- 25560061
TI  - Skin lesions in a lung cancer patient.

PMID- 25560062
TI  - Epstein-Barr virus-encoded RNA in-situ hybridization on non-specific ulcerative
      skin lesions of immunosuppressed patients.

PMID- 25560064
TI  - How FlAsH got its sparkle: historical recollections of the biarsenical
      tetracysteine tag.
AB  - The biarsenical-tetracysteine tagging system was the first of (and inspiration
      for) the now numerous methods for site-specifically labeling proteins in living
      cells with small molecules such as fluorophores. This historical recollection
      describes its conception and the trial-and-error chemical development required to
      become a versatile technique. 

PMID- 25560063
TI  - Improvement of encoding and retrieval in normal and pathological aging with word
      picture paradigm.
AB  - OBJECTIVES: During the aging process, there is a progressive deficit in the
      encoding of new information and its retrieval. Different strategies are used in
      order to maintain, optimize or diminish these deficits in people with and without
      dementia. One of the classic techniques is paired-associate learning (PAL), which
      is based on improving the encoding of memories, but it has yet to be used to its
      full potential in people with dementia. In this study, our aim is to corroborate
      the importance of PAL tasks as instrumental tools for creating contextual cues,
      during both the encoding and retrieval phases of memory. Additionally, we aim to
      identify the most effective form of presenting the related items. METHOD: Pairs
      of stimuli were shown to healthy elderly people and to patients with moderate and
      mild Alzheimer's disease. The encoding conditions were as follows: word/word,
      picture/picture, picture/word, and word/picture. RESULTS: Associative cued recall
      of the second item in the pair shows that retrieval is higher for the
      word/picture condition in the two groups of patients with dementia when compared
      to the other conditions, while word/word is the least effective in all cases.
      CONCLUSION: These results confirm that PAL is an effective tool for creating
      contextual cues during both the encoding and retrieval phases in people with
      dementia when the items are presented using the word/picture condition. In this
      way, the encoding and retrieval deficit can be reduced in these people.

PMID- 25560065
TI  - Site-specific protein labeling in the pharmaceutical industry: experiences from
      novartis drug discovery.
AB  - Chemically modified proteins play an important role in several fields of
      pharmaceutical R&D, starting from various activities in drug discovery all the
      way down to biopharmaceuticals with improved properties such as antibody-drug
      conjugates. In the first part of the present chapter the significance and use of
      labeled proteins in biophysical methods, biochemical and cellular assays, in vivo
      imaging, and biopharmaceuticals is reviewed in general. In this context, the most
      relevant methods for site-specific modification of proteins and their application
      are also described. In the second part of the chapter, in-house (Novartis)
      results and experience with different techniques for selective protein labeling
      are discussed, with a focus on chemical or enzymatic (Avi-tag) biotinylation of
      proteins and their application in biophysical and biochemical assays. It can be
      concluded that while modern methods of site-specific protein labeling offer new
      possibilities for pharmaceutical R&D, classical methods are still the mainstay
      mainly due to being well established. However, site-specific protein labeling is
      expected to increase in importance, in particular for antibody-drug conjugates
      and other chemically modified biopharmaceuticals. 

PMID- 25560067
TI  - Considerations and protocols for the synthesis of custom protein labeling probes.
AB  - Chemists and biologists have long recognized small molecule probes as powerful
      tools for functional genomics and proteomics studies. The possibility of
      specifically attaching chemical probes to individual proteins with spatial and
      temporal resolution has greatly improved our ability to visualize and
      characterize proteins in their native environment. The continued development of
      novel molecular probes for protein labeling is, therefore, of fundamental
      importance to gain new insights into biological processes in living cells and
      organisms. Several excellent approaches for the site-specific labeling of fusion
      proteins with chemical probes exist. Herein I discuss the design and generation
      of chemical probes for the SNAP-tag and CLIP-tag systems. The first part of this
      chapter is dedicated to reviewing the principles of the SNAP-tag technology,
      followed by a section dedicated to the development of chemical probes for unique
      applications, such as super-resolution imaging, protein trafficking and
      recycling, protein-protein interactions, and biomolecular sensing. The last part
      of the chapter contains experimental protocols and technical notes for the
      synthesis of selected SNAP-tag substrates and labeling of SNAP-tag fusion
      proteins in vitro and in living cells. 

PMID- 25560068
TI  - 2-Cyanobenzothiazole (CBT) condensation for site-specific labeling of proteins at
      the terminal cysteine residues.
AB  - Site specificity is pivotal in obtaining homogeneously labeled proteins without
      batch-to-batch variations. More importantly, precisely controlled modification at
      specific sites avoids potential pitfalls that could otherwise interfere with
      protein folding, structure, and function. Inspired by the chemical synthesis of D
      luciferin, we have developed an efficient strategy (second-order rate constant k
      2 = 9.2 M(-1) s(-1)) for labeling of proteins containing 1,2-aminothiol via
      reaction with 2-cyanobenzothiazole (CBT). In addition, the CBT condensation
      enjoys the convenience of protein engineering, as production of N-terminal
      cysteine-containing proteins has been well developed for native chemical
      ligation. This protocol describes the preparation of Renilla luciferase (rLuc)
      with 1,2-aminothiol at either its N- or C-terminus, and site-specific labeling of
      rLuc with fluorescein or (18)F via CBT condensation. 

PMID- 25560069
TI  - Fluorescent labeling for patch-clamp fluorometry (PCF) measurements of real-time
      protein motion in ion channels.
AB  - Understanding the function of ion channels is a major goal of molecular
      neurophysiology. While standard electrophysiological methods are invaluable tools
      to investigate the gating of ion channels, the structural rearrangements that
      mediate the way a channel senses physiological signals and opens and closes its
      gates cannot be measured electrically in a direct way. Here, we describe a
      method, based on site-specific labeling of a channel of interest with an
      environmentally sensitive fluorophore, which makes it possible to monitor
      conformational changes of ion channels in biological membranes in real time. 

PMID- 25560070
TI  - Fluorescent labeling of SNAP-tagged proteins in cells.
AB  - One of the most prominent self-labeling tags is SNAP-tag. It is an in vitro
      evolution product of the human DNA repair protein O (6)-alkylguanine-DNA
      alkyltransferase (hAGT) that reacts specifically with benzylguanine (BG) and
      benzylchloropyrimidine (CP) derivatives, leading to covalent labeling of SNAP-tag
      with a synthetic probe (Gronemeyer et al., Protein Eng Des Sel 19:309-316, 2006;
      Curr Opin Biotechnol 16:453-458, 2005; Keppler et al., Nat Biotechnol 21:86-89,
      2003; Proc Natl Acad Sci U S A 101:9955-9959, 2004). SNAP-tag is well suited for
      the analysis and quantification of fused target protein using fluorescence
      microscopy techniques. It provides a simple, robust, and versatile approach to
      the imaging of fusion proteins under a wide range of experimental conditions. 

PMID- 25560066
TI  - Getting across the cell membrane: an overview for small molecules, peptides, and
      proteins.
AB  - The ability to efficiently access cytosolic proteins is desired in both
      biological research and medicine. However, targeting intracellular proteins is
      often challenging, because to reach the cytosol, exogenous molecules must first
      traverse the cell membrane. This review provides a broad overview of how certain
      molecules are thought to cross this barrier, and what kinds of approaches are
      being made to enhance the intracellular delivery of those that are impermeable.
      We first discuss rules that govern the passive permeability of small molecules
      across the lipid membrane, and mechanisms of membrane transport that have evolved
      in nature for certain metabolites, peptides, and proteins. Then, we introduce
      design strategies that have emerged in the development of small molecules and
      peptides with improved permeability. Finally, intracellular delivery systems that
      have been engineered for protein payloads are surveyed. Viewpoints from varying
      disciplines have been brought together to provide a cohesive overview of how the
      membrane barrier is being overcome. 

PMID- 25560071
TI  - HaloTag technology for specific and covalent labeling of fusion proteins.
AB  - Appending proteins of interest to fluorescent protein tags such as GFP has
      revolutionized how proteins are studied in the cellular environment. Over the
      last few decades many varieties of fluorescent proteins have been generated, each
      bringing new capability to research. However, taking full advantage of standard
      fluorescent proteins with advanced and differential features requires significant
      effort on the part of the researcher. This approach necessitates that many
      genetic fusions be generated and confirmed to function properly in cells with the
      same protein of interest. To lessen this burden, a newer category of protein
      fusion tags termed "self-labeling protein tags" has been developed. This approach
      utilizes a single protein tag, the function of which can be altered by attaching
      various chemical moieties (fluorescent labels, affinity handles, etc.). In this
      way a single genetically encoded protein fusion can easily be given functional
      diversity and adaptability as supplied by synthetic chemistry. Here we present
      protein labeling methods using HaloTag technology; comprised of HaloTag protein
      and the collection of small molecules designed to bind it specifically and
      provide it with varied functionalities. For imaging purposes these small
      molecules, termed HaloTag ligands, contain distinct fluorophores. Due to covalent
      and rapid binding between HaloTag protein and its ligands, labeling is permanent
      and efficient. Many of these ligands have been optimized for permeability across
      cellular membranes allowing for live cell labeling and imaging analysis.
      Nonpermeable ligands have also been developed for specific labeling of surface
      proteins. Overall, HaloTag is a versatile technology that empowers the end user
      to label a protein of interest with the choice of different fluorophores while
      alleviating the need for generation of multiple genetic fusions. 

PMID- 25560072
TI  - Ligation of synthetic peptides to proteins using semisynthetic protein trans
      splicing.
AB  - Protein trans-splicing using split inteins is a powerful and convenient reaction
      to chemically modify recombinantly expressed proteins under mild conditions. In
      particular, semisynthetic protein trans-splicing with one intein fragment short
      enough to be accessible by solid-phase peptide synthesis can be used to transfer
      a short peptide segment with the desired synthetic moiety to the protein of
      interest. In this chapter, we provide detailed protocols for two such split
      intein systems. The M86 mutant of the Ssp DnaB intein and the MX1 mutant of the
      AceL-TerL intein are two highly engineered split inteins with very short N
      terminal intein fragments of only 11 and 25 amino acids, respectively, and allow
      the efficient N-terminal labeling of proteins. 

PMID- 25560073
TI  - Chemical-tag labeling of proteins using fully recombinant split inteins.
AB  - Chemical-tag labeling of proteins involving split inteins is an approach for the
      selective chemical modification of proteins without the requirement of any
      chemical synthesis to be performed. In a two-step protocol, a very short tag
      fused to a split intein auxiliary protein is first labeled in a bioconjugation
      reaction with a synthetic moiety either at its N-terminus (amine-tag) or at the
      side chain of an unnatural amino acid (click-tag). The labeled protein is then
      mixed with the protein of interest fused to the complementary intein fragment. In
      the resulting spontaneous protein trans-splicing reaction the split intein
      fragments remove themselves and ligate the tag to the protein of interest in a
      virtually traceless fashion. The reaction can be performed either using a
      purified protein of interest or to label a protein in the context of a living
      cell. All protein components are recombinantly expressed and all chemical
      reagents are commercially available. 

PMID- 25560074
TI  - Phage selection assisted by Sfp phosphopantetheinyl transferase-catalyzed site
      specific protein labeling.
AB  - Phosphopantetheinyl transferases (PPTase) Sfp and AcpS catalyze a highly
      efficient reaction that conjugates chemical probes of diverse structures to
      proteins. PPTases have been widely used for site-specific protein labeling and
      live cell imaging of the target proteins. Here we describe the use of PPTase
      catalyzed protein labeling in protein engineering by facilitating high-throughput
      phage selection. 

PMID- 25560076
TI  - Site-specific labeling of proteins via sortase: protocols for the molecular
      biologist.
AB  - Creation of site-specifically labeled protein bioconjugates is an important tool
      for the molecular biologist and cell biologist. Chemical labeling methods, while
      versatile with respect to the types of moieties that can be attached, suffer from
      lack of specificity, often targeting multiple positions within a protein. Here we
      describe protocols for the chemoenzymatic labeling of proteins at the C-terminus
      using the bacterial transpeptidase, sortase A. We detail a protocol for the
      purification of an improved pentamutant variant of the Staphylococcus aureus
      enzyme (SrtA 5(o)) that exhibits vastly improved kinetics relative to the wild
      type enzyme. Importantly, a protocol for the construction of peptide probes
      compatible with sortase labeling using techniques that can be adapted to any
      cellular/molecular biology lab with no existing infrastructure for synthetic
      chemistry is described. Finally, we provide an example of how to optimize the
      labeling reaction using the improved SrtA 5(o) variant. 

PMID- 25560075
TI  - Site-specific biotinylation of purified proteins using BirA.
AB  - The binding between biotin and streptavidin or avidin is one of the strongest
      known non-covalent biological interactions. The (strept)avidin-biotin interaction
      has been widely used for decades in biological research and biotechnology.
      Therefore labeling of purified proteins by biotin is a powerful way to achieve
      protein capture, immobilization, and functionalization, as well as multimerizing
      or bridging molecules. Chemical biotinylation often generates heterogeneous
      products, which may have impaired function. Enzymatic biotinylation with E. coli
      biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15
      amino acid AviTag peptide, giving a homogeneous product with high yield. AviTag
      can conveniently be added genetically at the N-terminus, C-terminus, or in
      exposed loops of a target protein. We describe here procedures for AviTag
      insertion by inverse PCR, purification of BirA fused to glutathione-S-transferase
      (GST-BirA) from E. coli, BirA biotinylation of purified protein, and gel-shift
      analysis by SDS-PAGE to quantify the extent of biotinylation. 

PMID- 25560077
TI  - BONCAT: metabolic labeling, click chemistry, and affinity purification of newly
      synthesized proteomes.
AB  - Metabolic labeling of proteins using classical radioisotope-labeled amino acids
      has enabled the analysis and function of protein synthesis for many biological
      processes but cannot be combined with modern high-throughput mass spectrometry
      analysis. This chapter describes the unbiased identification of a whole de novo
      synthesized proteome of cultured cells or of a translationally active subcellular
      fraction of the mammalian brain. This technique relies on the introduction of a
      small bioorthogonal reactive group by metabolic labeling accomplished by
      replacing the amino acid methionine by the azide-bearing methionine surrogate
      azidohomoalanine (AHA) or the amino acid homopropargylglycine (HPG). Subsequently
      an alkyne- or azide-bearing affinity tag is covalently attached to the group by
      "click chemistry"-a copper(I)-catalyzed [3+2] azide-alkyne cycloaddition.
      Affinity tag-labeled proteins can be analyzed in candidate-based approaches by
      conventional biochemical methods or with high-throughput mass spectrometry. 

PMID- 25560078
TI  - Genetic encoding of unnatural amino acids for labeling proteins.
AB  - The site-specific incorporation of bioorthogonal groups via genetic code
      expansion provides a powerful general strategy for site-specifically labeling
      proteins with any probe. Here we describe the genetic encoding of dienophile
      bearing unnatural amino acids into proteins expressed in Escherichia coli and
      mammalian cells using the pyrrolysyl-tRNA synthetase/tRNACUA pair and its
      variants. We describe the rapid fluorogenic labeling of proteins containing these
      unnatural amino acids in vitro, in E. coli, and in live mammalian cells with
      tetrazine-fluorophore conjugates in a bioorthogonal Diels-Alder reaction with
      inverse electron demand. These approaches have been extended to site-specific
      protein labeling in animals, and we anticipate that they will have a broad impact
      on the labeling and imaging field. 

PMID- 25560079
TI  - Labeling proteins by affinity-guided DMAP chemistry.
AB  - Catalysts have long played an essential role in organic synthesis and thus hold
      potential as tools for chemical protein modification. However, there are only a
      few examples of catalyst-mediated protein labeling under biological conditions
      because of the difficulty of designing molecular catalysts that work in aqueous
      environments with high target selectivity and reaction efficiency. To overcome
      this situation, we have previously developed a new catalyst-based method, termed
      affinity-guided DMAP (4-dimethylaminopyridine) (AGD) chemistry, for site-specific
      protein labeling in a target-selective manner using an acyl transfer reaction.
      More recently, we discovered that the labeling rate and efficiency can be greatly
      enhanced by using "multivalent" DMAP groups. Here, we describe the principle of
      the multivalent AGD chemistry and the protocol for chemical labeling of FK506
      binding protein 12 (FKBP12) in test tubes. In this method, the FKBP12 labeling is
      completed within 30 min and occurs site specifically at the vicinity of the
      ligand-binding pocket of the protein. 

PMID- 25560080
TI  - Ligand-directed tosyl chemistry for selective native protein labeling in vitro,
      in cells, and in vivo.
AB  - Introducing nongenetically encoded, synthetic probes into specific proteins is
      now recognized as a key component in chemical biology. In particular, the ability
      to chemically modify specific "native" proteins in various contexts from in vitro
      to cellular systems is of fundamental importance to study biological systems. We
      developed a protein-labeling technique termed ligand-directed tosyl (LDT)
      chemistry for this purpose. This method is capable of labeling specific native
      proteins with diverse synthetic probes with high site specificity and target
      selectivity without compromising protein function. Here we describe the principle
      of the LDT chemistry and the protocol for selective chemical labeling of native
      carbonic anhydrase in vitro, in blood cells (ex vivo), and in living mice (in
      vivo). 

PMID- 25560081
TI  - An anniversary year.

PMID- 25560082
TI  - Non-insulated microneedle fractional radiofrequency for the treatment of scars
      and photoaging.

PMID- 25560083
TI  - The quality-of-life benefits of breast reconstruction do not diminish with age.
AB  - BACKGROUND AND OBJECTIVES: Older women rarely receive post-mastectomy breast
      reconstruction (PMBR). While there is a perception that PMBR is less beneficial
      in this age group, quality-of-life (QOL) data related to PMBR in older women
      remain scarce. METHODS: Women with AJCC stage 0-III breast cancer who underwent a
      mastectomy were surveyed. Respondents included 215 older women (>= 65 years), of
      whom 36.0% received PMBR, and a control group of 101 younger women (< 65 years),
      all of whom received PMBR. Patient-reported outcomes were measured using the Duke
      Health Profile and the BREAST-Q. RESULTS: The survey response rate was 74.9%. An
      age-matched comparison of older women with and without PMBR revealed no
      significant differences in physical health, anxiety, or depression scores;
      however, PMBR was associated with greater breast satisfaction (P = 0.002) and
      greater breast-related psychosocial well-being (P = 0.02) than mastectomy alone.
      Among those who received PMBR, there was no correlation between age and breast
      satisfaction, psychosocial well-being, nor satisfaction with the outcome (P =
      0.11, 0.21, and 0.56). CONCLUSIONS: Older women who undergo PMBR have better
      breast-related QOL outcomes than those who do not. Moreover, the outcomes of PMBR
      in older women are similar to those seen in younger women. When appropriate,
      older women should be encouraged to consider PMBR.

PMID- 25560084
TI  - Extra tyrosine in the carbohydrate-binding module of Irpex lacteus Xyn10B
      enhances its cellulose-binding ability.
AB  - The xylanase (Xyn10B) that strongly adsorbs on microcrystalline cellulose was
      isolated from Driselase. The Xyn10B contains a Carbohydrate-binding module family
      1 (CBM1) (IrpCBMXyn10B) at N-terminus. The canonical essential aromatic residues
      required for cellulose binding were conserved in IrpCBMXyn10B; however, its
      adsorption ability was markedly higher than that typically observed for the CBM1
      of an endoglucanase from Trametes hirsuta (ThCBMEG1). An analysis of the CBM-GFP
      fusion proteins revealed that the binding capacity to cellulose (7.8 MUmol/g) and
      distribution coefficient (2.0 L/MUmol) of IrpCBMXyn10B-GFP were twofold higher
      than those of ThCBMEG1-GFP (3.4 MUmol/g and 1.2 L/MUmol, respectively), used as a
      reference structure. Besides the canonical aromatic residues (W24-Y50-Y51) of
      typical CBM1-containing proteins, IrpCBMXyn10B had an additional aromatic residue
      (Y52). The mutation of Y52 to Ser (IrpCBMY52S-GFP) reduced these adsorption
      parameters to 4.4 MUmol/g and 1.5 L/MUmol, which were similar to those of
      ThCBMEG1-GFP. These results indicate that Y52 plays a crucial role in strong
      cellulose binding.

PMID- 25560086
TI  - Two decades of experience with thoracoscopic lobectomy in infants and children:
      standardizing techniques for advanced thoracoscopic surgery.
AB  - OBJECTIVES: This study evaluates the safety and efficacy of thoracoscopic
      lobectomy in infants and children. MATERIALS AND METHODS: From January 1994 to
      November 2013, 347 patients underwent video-assisted thoracoscopic lobe resection
      at two institutions. All procedures were performed by or under the direct
      guidance of a single surgeon. Patients' ages ranged from 1 day to 18 years, and
      weights ranged from 2.8 to 78 kg. Preoperative diagnosis included
      sequestration/congenital pulmonary airway malformation (n=306), severe
      bronchiectasis (n=24), congenital lobar emphysema (n=13), and malignancy (n=4).
      RESULTS: Of the 347 procedures, 342 were completed thoracoscopically. Operative
      times ranged from 35 minutes to 240 minutes (average, 115 minutes). Average
      operative time when a trainee was the primary surgeon was 160 minutes. There were
      81 upper, 25 middle, and 241 lower lobe resections. There were four
      intraoperative complications (1.1%) requiring conversion to an open thoracotomy.
      The postoperative complication rate was 3.3%, and 3 patients required re
      exploration for a prolonged air leak. Hospital length of stay (LOS) ranged from 1
      to 16 days (average). In patients <5 kg and <3 months of age, the average
      operative time was 90 minutes, and the LOS was 2.1 days. CONCLUSIONS:
      Thoracoscopic lung resection is a safe and efficacious technique. With proper
      mentoring it is an exportable technique, which can be performed by pediatric
      surgical trainees. The procedures are safe and effective even when performed in
      the first 3 months of life. Early resection avoids the risk of later infection
      and malignancy.

PMID- 25560087
TI  - Oxygen reduction by lithiated graphene and graphene-based materials.
AB  - Oxygen reduction reaction (ORR) plays a key role in lithium-air batteries (LABs)
      that attract great attention thanks to their high theoretical specific energy
      several times exceeding that of lithium-ion batteries. Because of their high
      surface area, high electric conductivity, and low specific weight, various
      carbons are often materials of choice for applications as the LAB cathode.
      Unfortunately, the possibility of practical application of such batteries is
      still under question as the sustainable operation of LABs with carbon cathodes is
      not demonstrated yet and the cyclability is quite poor, which is usually
      associated with oxygen reduced species side reactions. However, the mechanisms of
      carbon reactivity toward these species are still unclear. Here, we report a
      direct in situ X-ray photoelectron spectroscopy study of oxygen reduction by
      lithiated graphene and graphene-based materials. Although lithium peroxide
      (Li2O2) and lithium oxide (Li2O) reactions with carbon are thermodynamically
      favorable, neither of them was found to react even at elevated temperatures. As
      lithium superoxide is not stable at room temperature, potassium superoxide (KO2)
      prepared in situ was used instead to test the reactivity of graphene with
      superoxide species. In contrast to Li2O2 and Li2O, KO2 was demonstrated to be
      strongly reactive. 

PMID- 25560085
TI  - Paclitaxel resistance increases oncolytic adenovirus efficacy via upregulated CAR
      expression and dysfunctional cell cycle control.
AB  - Resistance to paclitaxel chemotherapy frequently develops in ovarian cancer.
      Oncolytic adenoviruses are a novel therapy for human malignancies that are being
      evaluated in early phase trials. However, there are no reliable predictive
      biomarkers for oncolytic adenovirus activity in ovarian cancer. We investigated
      the link between paclitaxel resistance and oncolytic adenovirus activity using
      established ovarian cancer cell line models, xenografts with de novo paclitaxel
      resistance and tumour samples from two separate trials. The activity of multiple
      Ad5 vectors, including dl922-947 (E1A CR2-deleted), dl1520 (E1B-55K deleted) and
      Ad5 WT, was significantly increased in paclitaxel resistant ovarian cancer in
      vitro and in vivo. This was associated with greater infectivity resulting from
      increased expression of the primary receptor for Ad5, CAR (coxsackie adenovirus
      receptor). This, in turn, resulted from increased CAR transcription secondary to
      histone modification in resistant cells. There was increased CAR expression in
      intraperitoneal tumours with de novo paclitaxel resistance and in tumours from
      patients with clinical resistance to paclitaxel. Increased CAR expression did not
      cause paclitaxel resistance, but did increase inflammatory cytokine expression.
      Finally, we identified dysregulated cell cycle control as a second mechanism of
      increased adenovirus efficacy in paclitaxel-resistant ovarian cancer. Ad11 and
      Ad35, both group B adenoviruses that utilise non-CAR receptors to infect cells,
      are also significantly more effective in paclitaxel-resistant ovarian cell
      models. Inhibition of CDK4/6 using PD-0332991 was able both to reverse paclitaxel
      resistance and reduce adenovirus efficacy. Thus, paclitaxel resistance increases
      oncolytic adenovirus efficacy via at least two separate mechanisms - if validated
      further, this information could have future clinical utility to aid patient
      selection for clinical trials.

PMID- 25560088
TI  - Learning to rank diversified results for biomedical information retrieval from
      multiple features.
AB  - BACKGROUND: Different from traditional information retrieval (IR), promoting
      diversity in IR takes consideration of relationship between documents in order to
      promote novelty and reduce redundancy thus to provide diversified results to
      satisfy various user intents. Diversity IR in biomedical domain is especially
      important as biologists sometimes want diversified results pertinent to their
      query. METHODS: A combined learning-to-rank (LTR) framework is learned through a
      general ranking model (gLTR) and a diversity-biased model. The former is learned
      from general ranking features by a conventional learning-to-rank approach; the
      latter is constructed with diversity-indicating features added, which are
      extracted based on the retrieved passages' topics detected using Wikipedia and
      ranking order produced by the general learning-to-rank model; final ranking
      results are given by combination of both models. RESULTS: Compared with baselines
      BM25 and DirKL on 2006 and 2007 collections, the gLTR has 0.2292 (+16.23% and
      +44.1% improvement over BM25 and DirKL respectively) and 0.1873 (+15.78% and
      +39.0% improvement over BM25 and DirKL respectively) in terms of aspect level of
      mean average precision (Aspect MAP). The LTR method outperforms gLTR on 2006 and
      2007 collections with 4.7% and 2.4% improvement in terms of Aspect MAP.
      CONCLUSIONS: The learning-to-rank method is an efficient way for biomedical
      information retrieval and the diversity-biased features are beneficial for
      promoting diversity in ranking results.

PMID- 25560089
TI  - Salvage for nail breakage in femoral intramedullary nailing.
AB  - Proximal fractures of femur represent an important cause of hospitalization,
      morbidity and mortality for elderly patients. Femoral intramedullary nailing is
      an option to achieve a stable osteosynthesis but the breakage is a rare
      complication. The aim was to determinate the prevalence, causes, management and
      functional outcomes of this patients in our hands. Retrospective review of 1246
      proximal femur fractures operated between 2003 and 2012. We analyse
      epidemiological data, fracture type and the quality of closed reduction and
      fixation by preoperative and postoperative radiology. Type of salvage procedure
      chosen for each case is presented. Functional outcome and quality of life
      questionnaire was obtained by Barthel index and Short Form 12 version 2. 11 cases
      (0.88%) were identified. The type of initial fracture was 7 cases AO/OTA 31A3 and
      4 cases AO/OTA 31A2. The implant failure was detected at 11 months after surgery
      (SD 6.39). Nail breakage occurred in three different points: 7 cases in the
      proximal aperture, 3 cases in cervicocephalic screw and 1 case in the distal
      aperture of the nail. The association of nonunion at fracture site and
      progressive hip pain was observed in all cases. Different salvage procedures were
      performed: 7 cases osteosynthesis revision (nail or dynamic condilar screw
      plate), 2 cases arthroplasty and 2 cases conservative treatment. The main Barthel
      score before the salvage procedure was 63.2 (SD 13). At final follow-up, this
      score improved to 72.8 (SD 20.38). To the best of our knowledge, this study
      represents the largest series of cases of trochanteric nail breakage due to
      material fatigue. This complication is rare (0.88%) that can foresee in unstable
      fractures with delayed union. The type of salvage should be individualized
      showing acceptable functional outcome in our series. 

PMID- 25560090
TI  - Concerns about fibrosis development after scaffolded PRP therapy of muscle
      injuries: commentary on an article by Sanchez et al.: "Muscle repair: platelet
      rich plasma derivates as a bridge from spontaneity to intervention.".

PMID- 25560091
TI  - Correlations between homocysteine and grey matter volume in patients with
      Alzheimer's disease.
AB  - BACKGROUND: Previous studies have reported that elevated total homocysteine
      levels are associated with cognitive dysfunction. However, few studies have
      examined the radiological markers of associated neuropathology in Alzheimer's
      disease (AD). We hypothesized that elevated levels of homocysteine are associated
      with cerebral grey matter volume loss. We compared the grey matter in a high
      homocysteine group and a normal homocysteine group using an optimized voxel-based
      morphometry. METHODS: The study included 79 patients with AD who were divided
      into two groups: a high homocysteine group and a normal homocysteine group. The
      participants underwent brain magnetic resonance imaging using a standardized
      protocol and neurocognitive evaluation. Homocysteine tests and other routine
      laboratory examinations for dementia assessment were carried out in all patients.
      RESULTS: There was no significant difference in grey matter volume between the
      patients with high homocysteine levels and those with normal homocysteine levels.
      A multiple regression analysis also revealed that the levels of homocysteine were
      not associated with the grey matter volume in patients with AD. Homocysteine
      levels were not correlated significantly with Mini-Mental State Examination,
      Global Deterioration Scale, or Clinical Dementia Rating. CONCLUSION: Our results
      showed that elevated homocysteine levels are not associated with reduced cerebral
      grey matter volume in AD. Larger samples will be needed to assess potential
      correlations between homocysteine and neuroanatomical pathology in the future.

PMID- 25560092
TI  - Uptake of evidence in policy development: the case of user fees for health care
      in public health facilities in Uganda.
AB  - BACKGROUND: Several countries in Sub Saharan Africa have abolished user fees for
      health care but the extent to which such a policy decision is guided by evidence
      needs further exploration. We explored the barriers and facilitating factors to
      uptake of evidence in the process of user fee abolition in Uganda and how the
      context and stakeholders involved shaped the uptake of evidence. This study
      builds on previous work in Uganda that led to the development of a middle range
      theory (MRT) outlining the main facilitating factors for knowledge translation
      (KT). Application of the MRT to the case of abolition of user fees contributes to
      its refining. METHODS: Employing a theory-driven inquiry and case study approach
      given the need for in-depth investigation, we reviewed documents and conducted
      interviews with 32 purposefully selected key informants. We assessed whether
      evidence was available, had or had not been considered in policy development and
      the reasons why and; assessed how the actors and the context shaped the uptake of
      evidence. RESULTS: Symbolic, conceptual and instrumental uses of evidence were
      manifest. Different actors were influenced by different types of evidence. While
      technocrats in the ministry of health (MoH) relied on formal research,
      politicians relied on community complaints. The capacity of the MoH to lead the
      KT process was weak and the partnerships for KT were informal. The political
      window and alignment of the evidence with overall government discourse enhanced
      uptake of evidence. Stakeholders were divided, seemed to be polarized for various
      reasons and had varying levels of support and influence impacting the uptake of
      evidence. CONCLUSION: Evidence will be taken up in policy development in
      instances where the MoH leads the KT process, there are partnerships for KT in
      place, and the overall government policy and the political situation can be
      expected to play a role. Different actors will be influenced by different types
      of evidence and their level of support and influence will impact the uptake of
      evidence. In addition, the extent to which a policy issue is contested and,
      whether stakeholders share similar opinions and preferences will impact the
      uptake of evidence.

PMID- 25560093
TI  - Impact of incidental findings on integrated 2-[18F]-fluoro-2-deoxy-D-glucose
      positron emission tomography/computed tomography in patients with gastric cancer.
AB  - AIM: Since positron emission tomography/computed tomography (PET/CT) has been
      introduced, many incidental findings have been identified. The aim of this study
      was to assess the clinical significance of incidental findings on PET/CT in
      patients with gastric cancer. METHODS: A total of 421 patients with gastric
      cancer underwent PET/CT for initial staging. Incidental findings on PET/CT were
      classified into five categories according to clinical significance--normal
      variant, benign, probably benign, probably malignant, and definitely malignant.
      We obtained information regarding follow-up examinations, additional visits,
      final diagnosis of incidental findings and short-term medical costs for further
      evaluation. RESULTS: Eight hundred eighty-two incidental findings were detected
      in 386 (91.7%) patients. Of 274 incidental findings classified as probably
      benign, probably malignant or definitely malignant, 130 required one or more
      additional investigations. Finally, 12 (9.2%) were proved to be associated with
      second primary malignancy or metastasis of gastric cancer. One hundred twenty
      nine additional outpatient visits and 10 additional hospitalizations were needed
      for evaluating the incidental findings. The treatment strategy for gastric cancer
      was changed in one patient. The estimated cost of additional investigations was
      $US283 (95% CI: $US248-$US311) per patient. CONCLUSION: Incidental findings on
      PET/CT were common. Although the incidental findings were suspicious of
      malignancy, most were benign with high costs for additional investigations.

PMID- 25560094
TI  - Nanostructured multifunctional surface with antireflective and antimicrobial
      characteristics.
AB  - Functional polymeric films with antireflective and hydrophobic properties have
      been widely used for electronic device displays. However, the design of such
      functional films with an antimicrobial characteristic has been a challenge. We
      designed a nanostructured surface using a rigorous coupled-wave analysis to
      obtain a period of 300 nm and an aspect ratio of 3.0 on a flat poly(methyl
      methacrylate) film. The fabricated nanostructure was hydrophobic and exhibited
      the desired optical characteristics with a reflectance of less than 0.5% over the
      visible wavelength range. Furthermore, the nanoimprinted polymer film exhibited
      antimicrobial characteristics and low adhesion when compared with the
      corresponding flat surface. The results suggest that the nanostructured surface
      designed in this study is multifunctional and should be suitable for the
      production of protective optical and hygienic polymer films for the displays of
      portable electronic devices. 

PMID- 25560096
TI  - Enough already!

PMID- 25560098
TI  - Peripartum venous thromboembolism prophylaxis: where do we go from here?

PMID- 25560097
TI  - Pregnancy-related mortality in the United States, 2006-2010.
AB  - OBJECTIVE: To update national population-level pregnancy-related mortality
      estimates and examine characteristics and causes of pregnancy-related deaths in
      the United States during 2006-2010. METHODS: We used data from the Pregnancy
      Mortality Surveillance System and calculated pregnancy-related mortality ratios
      by year and age group for four race-ethnicity groups: non-Hispanic white, non
      Hispanic black, Hispanic, and other. We examined causes of pregnancy-related
      deaths by pregnancy outcome during 2006-2010 and compared causes of pregnancy
      related deaths since 1987. RESULTS: The 2006-2010 pregnancy-related mortality
      ratio was 16.0 deaths per 100,000 live births (20,959,533 total live births).
      Specific race-ethnicity pregnancy-related mortality ratios were 12.0, 38.9, 11.7,
      and 14.2 deaths per 100,000 live births for non-Hispanic white, non-Hispanic
      black, Hispanic, and other race women, respectively. Pregnancy-related mortality
      ratios increased with maternal age for all women and within all age groups, non
      Hispanic black women had the highest risk of dying from pregnancy complications.
      Over time, the contribution to pregnancy-related deaths of hemorrhage,
      hypertensive disorders of pregnancy, embolism, and anesthesia complications
      continued to decline, whereas the contribution of cardiovascular conditions and
      infection increased. Seven of 10 categories of causes of death each contributed
      from 9.4% to 14.6% of all 2006-2010 pregnancy-related deaths; cardiovascular
      conditions ranked first. CONCLUSION: Relative to previous years, during 2006
      2010, the U.S. pregnancy-related mortality ratio increased as did the
      contribution of cardiovascular conditions and infection to pregnancy-related
      mortality. Although the identification of pregnancy-related deaths may be
      improving in the United States, the increasing contribution of chronic diseases
      to pregnancy-related mortality suggests a change in risk profile of the birthing
      population. LEVEL OF EVIDENCE: II.

PMID- 25560099
TI  - Sequential compression device compliance in postoperative obstetrics and
      gynecology patients.
AB  - OBJECTIVE: To assess the association of patient and nursing education on
      sequential compression device compliance in patients who have undergone major
      obstetric or benign gynecologic procedures. METHODS: We performed a prospective
      observational study on all English-speaking patients who underwent cesarean
      delivery or benign gynecologic surgery and were prescribed to wear sequential
      compression devices postoperatively at a university medical center. The 4-month
      study was divided into 1-month segments. The first month consisted of baseline
      observations of compliance. The second month was comprised of structured patient
      education, the third month involved nursing education, and the final month
      included both interventions. Observations were made twice daily. All educational
      interventions and observations were performed by two coauthors. A patient was
      noted to be compliant if she was ambulating, sitting, or lying in bed with
      sequential compression devices applied, tubing attached, and the machine powered
      on. RESULTS: A total of 859 observations was recorded for 228 patients. The
      number of hospitalization days ranged from 1 to 13 (mean 2.40 days, median 2
      days). There was no difference in compliance among the months with 141 of 230
      (61.3%), 106 of 194 (54.6%), 155 of 277 (56.0%), and 95 of 158 (60.1%) compliance
      for each consecutive month (P=.44). Noncompliance increased with each successive
      postoperative day (odds ratio 1.18 per day, 95% confidence interval 1.07-1.30).
      The most common patient-stated reason for noncompliance was "the nurse said I
      don't need them anymore" (82/362 observations [22.6%]). Overall, cesarean
      delivery was associated with the lowest rate of compliance when compared with
      gynecologic surgeries (272/519 [52.4%] compared with 225/340 [66.2%], P<.001).
      CONCLUSION: Compliance with postoperative use of sequential compression devices
      is approximately 58% and did not improve with patient or nursing educational
      interventions. LEVEL OF EVIDENCE: III.

PMID- 25560100
TI  - Postoperative pain after adjustable single-incision or transobturator sling for
      incontinence: a randomized controlled trial.
AB  - OBJECTIVE: To compare postoperative pain scores and assess efficacy between an
      adjustable single-incision sling and a standard transobturator sling for stress
      urinary incontinence (SUI). METHODS: This single-blinded randomized controlled
      trial involved 156 women with clinically proven SUI. Women were allocated to
      receive either an adjustable single-incision or a transobturator sling. The
      primary outcome was postoperative pain score on a visual analog scale. Secondary
      outcomes were objective and subjective cure rates at 12 months, symptom bother
      scores, quality of life, and complications. RESULTS: The mean pain score in the
      first week postoperatively was significantly lower at all time points in the
      adjustable single-incision sling group compared with the transobturator sling
      group. Maximum difference in pain score was reported on the evening of the day of
      surgery; median pain score was 1.0 (interquartile range 2.0) in the adjustable
      sling group and 3.0 (interquartile range 4.5) in the transobturator sling group
      (Mann Whitney U test P<.001). There was no statistical difference in analgesic
      use. The objective cure rates in the adjustable single-incision sling and in the
      transobturator sling group were 90.8% and 88.6% (P=.760), and the subjective cure
      rates were 77.2% and 72.9% (P=.577), respectively. No difference in the
      complication rate was found. CONCLUSION: An adjustable single-incision sling for
      the treatment of SUI is associated with lower early postoperative pain scores but
      shows comparable cure rates with a transobturator at 12 months of follow-up.
      CLINICAL TRIAL REGISTRATION: Netherlands Trial Register,
      http://www.trialregister.nl, NTR: 2558. LEVEL OF EVIDENCE: I.

PMID- 25560101
TI  - The burden of nocturia among middle-aged and older women.
AB  - OBJECTIVE: To examine the prevalence, predictors, and effects of nocturia in
      women and evaluate overlaps with established urinary tract disorders. METHODS:
      This was a cross-sectional analysis of 2,016 women, aged 40 years and older,
      recruited from Kaiser Permanente Northern California from 2008 to 2012. Nocturia
      and other urinary symptoms were assessed using structured interviewer
      administered questionnaires. Nocturia was defined as patient-reported nocturnal
      voiding of two or more times per night over a typical week. RESULTS: Thirty-four
      percent (n=692) reported nocturia, and 40% of women with nocturia reported no
      other urinary tract symptom. Women with nocturia were older (mean age 58 compared
      with 55 years) (odds ratio [OR] per 5-year increase 1.21, 95% confidence interval
      [CI] 1.12-1.31), more likely black (45%) (OR 1.75, 95% CI 1.30-2.35) or Latina
      (37%) (OR 1.36, 95% CI 1.02-1.83) compared with non-Latina white (30%), have
      worse depression (mean Hospital Anxiety and Depression Scale score 3.8 compared
      with 2.8) (OR per 1-point increase in Hospital Anxiety and Depression Scale score
      1.08, 95% CI 1.04-1.12), and worse mobility (mean Timed Up-and-Go 11.3 compared
      with 10 seconds) (OR per 5-second increase in Timed Up-and-Go 1.29, 95% CI 1.05
      1.58). Nocturia occurred more among women with hysterectomy (53% compared with
      33%) (OR 1.78, 95% CI 1.08-2.94), hot flushes (38% compared with 32%) (OR 1.49,
      95% CI 1.19-1.87), and vaginal estrogen use (42% compared with 34%) (OR 1.50, 95%
      CI 1.04-2.18). CONCLUSION: Nocturia is common in women and not necessarily
      attributable to other urinary tract disorders. Factors not linked to bladder
      function may contribute to nocturia risk, underlining the need for multiorgan
      prevention and treatment strategies. LEVEL OF EVIDENCE: II.

PMID- 25560103
TI  - Complete procidentia: temporizing treatment with an obstetric balloon.
AB  - BACKGROUND: Pelvic organ incarceration resulting from complete uterovaginal
      prolapse is rare. Unique management and treatment of this condition are
      presented. CASE: A 66-year-old multigravid woman presented with increasing
      abdominal pain, 1-day history of urinary retention, and 30-day history of
      obstipation. She exhibited complete procidentia, and an attempt to reduce the
      prolapse immediately was unsuccessful. After fecal disimpaction in the operating
      room, an obstetric balloon was used for temporary reduction. CONCLUSION:
      Incarcerated complete procidentia is treated in a stepwise process, initially
      reducing the prolapse to relieve acute incarceration symptoms. Typically,
      reduction is accomplished with the aid of a pessary. However, because of this
      patient's condition, an obstetric balloon was used for temporary reduction to
      allow subsequent surgical treatment after tissue rest and medical stabilization.
      This method should be considered in similar situations.

PMID- 25560102
TI  - Mesh sacrocolpopexy compared with native tissue vaginal repair: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To systematically review outcomes after mesh sacrocolpopexy compared
      with native tissue vaginal repairs in women with apical prolapse. DATA SOURCES:
      We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials,
      and ClinicalTrials.gov through June 4, 2012. METHODS OF STUDY SELECTION: For
      anatomic and functional analyses, we included studies comparing mesh
      sacrocolpopexy to native tissue vaginal repairs with at least 6 months follow-up.
      The primary outcome was anatomic "success" after surgery. Secondary outcomes were
      reoperation and symptom outcomes. We included large case series and comparative
      studies with shorter follow-up to increase power for adverse event analyses.
      TABULATION, INTEGRATION, AND RESULTS: Evidence quality was assessed with the
      Grades for Recommendation, Assessment, Development and Evaluation system. Meta
      analyses were performed when at least three studies reported the same outcome. We
      included 13 comparative studies for anatomic success, reoperation, and symptom
      outcomes. Moderate-quality evidence supports improved anatomic outcomes after
      mesh sacrocolpopexy; very low-quality evidence shows no differences in
      reoperation between sacrocolpopexy and native tissue vaginal repairs. Evidence
      was insufficient regarding which procedures result in improved bladder or bowel
      symptoms. Low-quality evidence showed no differences in postoperative sexual
      function. Adverse event data were compiled and meta-analyzed from 79 studies.
      When including larger noncomparative studies, ileus or small bowel obstruction
      (2.7% compared with 0.2%, P<.01), mesh or suture complications (4.2% compared
      with 0.4%, P<.01), and thromboembolic phenomena (0.6% compared with 0.1%, P=.03)
      were more common after mesh sacrocolpopexy compared with native tissue vaginal
      repairs. CONCLUSION: When anatomic durability is a priority, we suggest that mesh
      sacrocolpopexy may be the preferred surgical option. When minimizing adverse
      events or reoperation is the priority, there is no strong evidence supporting one
      approach over the other.

PMID- 25560104
TI  - Removing a misplaced retropubic midurethral sling from the urethra and bladder
      neck using ear, nose, and throat instruments.
AB  - BACKGROUND: The retropubic tension-free vaginal tape (TVT) procedure is a common
      procedure with complications attributed to voiding dysfunction, bladder
      perforation, and bleeding. We present a case of successful removal of a
      retropubic midurethral sling from the urethra using a head lamp and a combination
      of ear, nose, and throat instruments. CASE: A 63-year-old woman presented to our
      clinic with the symptom of gross hematuria after having undergone a TVT
      procedure. On office cystoscopy, the sling was noted to be placed within the
      urethral mucosa. Removal of the mesh was performed using a nasal speculum, left
      and right ethmoid scissors, left and right Blakesley graspers, and a head lamp to
      dissect the mesh directly out of the urethra. CONCLUSION: The utilization of ear,
      nose, and throat tools allowed us to resect the intraurethral mesh without
      necessitating incision of the urethral sphincter.

PMID- 25560105
TI  - Obturator neuropathy after retropubic tension-free vaginal tape placement.
AB  - BACKGROUND: We report a case of obturator neuropathy associated with retropubic
      midurethral sling. CASE: After retropubic tension-free vaginal tape (TVT)
      placement, a 36-year-old woman reported right inguinal region and thigh pain,
      both exacerbated with internal rotation and adduction. Neurologic examination was
      remarkable for two-fifths strength with right thigh adduction and an involuntary
      lateral drift of her right thigh with straight leg raise. Radiologic evaluation
      was unrevealing. With persistence of motor symptoms and pain, partial sling
      removal on the right was performed. Symptoms subsided postoperatively, and the
      patient ultimately recovered with no residual neurologic sequelae. CONCLUSION:
      Recognition of an atypical complication, obturator neuropathy, of retropubic TVT
      placement with prompt partial right sling removal on postoperative day 2 resulted
      in complete recovery of neurologic sequelae.

PMID- 25560106
TI  - Situational awareness and its application in the delivery suite.
AB  - The delivery suite is a high-risk environment. Transitions between low-risk and
      high-risk can be swift, and sentinel events can occur without warning. The
      prevention of accidents in this environment rests on the vigilance of the
      individual practitioner at the frontline. It is, therefore, important that the
      individual practitioner should develop and maintain the cognitive skills to
      anticipate, recognize, and intercept unfolding error chains. This commentary
      gives an overview of a nontechnical skill that is essential for safe practice in
      a delivery suite: situational awareness. A basic description of situational
      awareness is provided, using examples of loss of situational awareness in the
      delivery suite and examples of simple interventions that could promote
      situational awareness. Involuntary automaticity readily creeps in during
      performance of routine tasks, and cognitive overload could deplete attentional
      resources that are, by nature, limited. Strategies and tactics for maintaining
      situational awareness include proactively seeking and managing information on
      unfolding events, continually updating individual and team mental models, mindful
      use of checklists and scoreboards, and avoidance of attentional blindness. These
      simple interventions require minimal financial resources but could immensely
      enhance clinical performance and patient safety. Situational awareness should be
      included in the training of obstetrician-gynecologists and other staff working in
      a delivery suite.

PMID- 25560107
TI  - Risk of ectopic pregnancy associated with assisted reproductive technology in the
      United States, 2001-2011.
AB  - OBJECTIVE: To assess national trends in ectopic pregnancy incidence among
      assisted reproductive technology users and identify risk factors associated with
      ectopic pregnancy. METHODS: We identified 553,577 pregnancies reported to the
      National ART Surveillance System between 2001 and 2011. Of those, 9,480 were
      ectopic, of which 485 were heterotopic. As a result of small numbers, ectopic and
      heterotopic pregnancies were combined for analysis. We assessed temporal trends
      in annual ectopic pregnancy rates using Poisson regression. We used log-binomial
      regression models with generalized estimating equations for correlated outcomes
      within clinics to calculate unadjusted and adjusted risk ratios for the
      association between ectopic pregnancy and selected patient characteristics and
      treatment factors. RESULTS: The rate of ectopic pregnancy declined from 2.0%
      (n=735, 95% confidence interval [CI] 1.9-2.2) in 2001 to 1.6% (n=968, 95% CI 1.5
      1.7) in 2011 (P for trend <.001). The ectopic pregnancy rate ranged from 2.0%
      (n=7,469, 95% CI 1.9-2.0) for fresh, nondonor cycles to 1.0% (n=641, 95% CI 0.9
      1.1) for fresh, donor cycles. Among fresh, nondonor cycles, the rate of ectopic
      pregnancy was 1.6% (95% CI 1.4-1.7) when one embryo was transferred compared with
      1.7% (95% CI 1.7-1.8), 2.2% (95% CI 2.1-2.3), and 2.5% (95% CI 2.4-2.6) when two,
      three, or four or more embryos were transferred, respectively (adjusted risk
      ratios 1.11, 95% CI 0.94-0.30; 1.33, 95% CI 1.12-1.56; and 1.49, 95% CI 1.25
      1.78). CONCLUSION: Ectopic pregnancy incidence after assisted reproductive
      technology has decreased over time, but factors such as multiple embryo transfer
      increase the risk of ectopic pregnancy. LEVEL OF EVIDENCE: II.

PMID- 25560108
TI  - Influence of endometriosis on assisted reproductive technology outcomes: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To investigate the association of endometriosis on assisted
      reproductive technology (ART) outcomes and to review if surgical treatment of
      endometriosis before ART affects the outcomes. DATA SOURCES: We searched studies
      published between 1980 and 2014 on endometriosis and ART outcome. We searched
      MEDLINE, PubMed, ClinicalTrials.gov, and Cochrane databases and performed a
      manual search. METHODS OF STUDY SELECTION: A total of 1,346 articles were
      identified, and 36 studies were eligible to be included for data synthesis. We
      included published cohort studies and randomized controlled trials. TABULATION,
      INTEGRATION, AND RESULTS: Compared with women without endometriosis, women with
      endometriosis undertaking in vitro fertilization and intracytoplasmic sperm
      injection have a similar live birth rate per woman (odds ratio [OR] 0.94, 95%
      confidence interval [CI] 0.84-1.06, 13 studies, 12,682 patients, I=35%), a lower
      clinical pregnancy rate per woman (OR 0.78, 95% CI 0.65-0.94), 24 studies, 20,757
      patients, I=66%), a lower mean number of oocyte retrieved per cycle (mean
      difference -1.98, 95% CI -2.87 to -1.09, 17 studies, 17,593 cycles, I=97%), and a
      similar miscarriage rate per woman (OR 1.26, 95% CI (0.92-1.70, nine studies,
      1,259 patients, I=0%). Women with more severe disease (American Society for
      Reproductive Medicine III-IV) have a lower live birth rate, clinical pregnancy
      rate, and mean number of oocytes retrieved when compared with women with no
      endometriosis. CONCLUSION: Women with and without endometriosis have comparable
      ART outcomes in terms of live births, whereas those with severe endometriosis
      have inferior outcomes. There is insufficient evidence to recommend surgery
      routinely before undergoing ART.

PMID- 25560109
TI  - Family history and risk of endometrial cancer: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To obtain precise estimates of endometrial cancer risk associated with
      a family history of endometrial cancer or cancers at other sites. DATA SOURCES:
      For the systematic review, we used PubMed to search for all relevant studies on
      family history and endometrial cancer that were published before December 2013.
      Medical Subject Heading terms "endometrial neoplasm" and "uterine neoplasm" were
      used in combination with one of the key phrases "family history," "first-degree,"
      "familial risk," "aggregation," or "relatedness." METHODS OF STUDY SELECTION:
      Studies were included if they were case-control or cohort studies that
      investigated the association between a family history of cancer specified to site
      and endometrial cancer. Studies were excluded if they were review or editorial
      articles or not translated into English or did not define family history clearly
      or used spouses as control participants. TABULATION, INTEGRATION, AND RESULTS: We
      included 16 studies containing 3,871 women as cases and 49,475 women as controls
      from 10 case-control studies and 33,510 women as cases from six cohort studies.
      We conducted meta-analyses to estimate the pooled relative risk (95% confidence
      interval [CI]) of endometrial cancer associated with a first-degree family
      history of endometrial, colorectal, breast, ovarian, and cervical cancer to be:
      1.82 (1.65-1.98), 1.17 (1.03-1.31), 0.96 (0.88-1.04), 1.13 (0.85-1.41), and 1.19
      (0.83-1.55), respectively. We estimated cumulative risk of endometrial cancer to
      age 70 years to be 3.1% (95% CI 2.8-3.4) for women with a first-degree relative
      with endometrial cancer and the population-attributable risk to be 3.5% (95% CI
      2.8-4.2). CONCLUSION: Women with a first-degree family history of endometrial
      cancer or colorectal cancer have a higher risk of developing endometrial cancer
      than those without a family history. This study is likely to be of clinical
      relevance to inform women of their risk of endometrial cancer.

PMID- 25560110
TI  - Surgical cytoreduction for disseminated benign disease after open power uterine
      morcellation.
AB  - BACKGROUND: Uterine morcellation is a technique used in gynecologic surgery to
      facilitate a laparoscopic approach to the removal of an enlarged uterus. The
      safety of this technique has been a source of recent debate, as uterine
      morcellation can result in the intraperitoneal dissemination of undiagnosed
      uterine malignancies. CASES: We report on three women who previously underwent
      minimally invasive hysterectomy and open power morcellation for benign disease,
      who subsequently presented with peritoneal implants highly suspicious for
      malignancy. Each woman required a laparotomy and extensive, multiorgan resection
      to clear the disease. Benign pathology was diagnosed in all cases. CONCLUSION:
      Even in the setting of benign conditions, open power morcellation of the uterus
      may be associated with clinically significant dissemination of uterine disease.

PMID- 25560111
TI  - Association of prelabor cesarean delivery with reduced mortality in twins born
      near term.
AB  - OBJECTIVE: To examine short-term and longer-term outcomes for twins born at or
      near term, comparing prelabor cesarean delivery with birth after a trial of
      labor. METHODS: This study was conducted on a retrospective cohort of twin
      pregnancies delivered at 36 weeks of gestation or greater from 2000 to 2009.
      Pregnancies with an antenatal death, lethal anomaly, birth weight discordance 25%
      or more, or birth weight less than 2,000 g or more than 4,000 g were excluded.
      Outcomes included severe hypoxia, stillbirth and neonatal death, and hospital
      admissions or death during the first 5 years of life. RESULTS: Approximately 45%
      of 7,099 twin pregnancies were delivered by prelabor cesarean delivery. Compared
      with delivery after labor, prelabor cesarean delivery was associated with
      significantly reduced risks of adverse neonatal and child outcomes including
      severe birth hypoxia (0.08% compared with 0.75%, relative risk 0.10, 95%
      confidence interval [CI] 0.04-0.26), neonatal death (0.00% compared with 0.15%,
      relative risk 0.05, 95% CI 0.00-0.82), and death up to 5 years of age (0.16%
      compared with 0.40%, relative risk 0.41, 95% CI 0.20-0.85). Whereas total
      mortality for first twins was similar after labor (0.15%) compared with prelabor
      cesarean delivery (0.16%), total mortality was four times more common in second
      twins born after labor (0.64%) compared with second twins born after prelabor
      cesarean delivery (0.16%). CONCLUSION: Compared with prelabor cesarean delivery,
      twin pregnancies at and beyond 36 weeks of gestation delivered after labor have
      increased risks for birth outcomes associated with hypoxia, with second twins
      having significantly increased mortality up to 5 years of age. However, the
      absolute mortality rate for relatively uncomplicated twin pregnancies delivered
      at or near term is low and needs to be balanced against maternal morbidity. LEVEL
      OF EVIDENCE: II.

PMID- 25560112
TI  - Trends and correlates of monozygotic twinning after single embryo transfer.
AB  - OBJECTIVE: To evaluate trends of monozygotic twinning after single embryo
      transfer and its association with patient and treatment factors. METHODS: Our
      retrospective cohort study included 28,596 pregnancies after fresh, nondonor
      single embryo transfer during 2003-2012 reported to the National ART Surveillance
      System. We examined trends of monozygotic twin pregnancies (number of fetal heart
      tones on first-trimester ultrasonography more than one or number of neonates born
      more than one) and assessed patient and treatment factors for monozygotic twin
      compared with singleton pregnancies. Modified Poisson regression models were used
      to estimate adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for
      association between monozygotic twinning and selected factors stratified by day 2
      3 and day 5-6 transfer. RESULTS: During 2003-2012, the incidence of monozygotic
      twinning after single embryo transfer was lower for day 2-3 transfers than for
      day 5-6 transfers (1.71%, 95% CI 1.45-1.98, n=162 compared with 2.50%, 95% CI
      2.28-2.73, n=472); the incidence did not change significantly over the study
      period. Among day 2-3 transfers, assisted hatching increased the risk for
      monozygotic twinning compared with singletons (adjusted RR 2.16, 95% CI 1.53
      3.06); use of intracytoplasmic sperm injection decreased the risk (adjusted RR
      0.60, 95% CI 0.42-0.85). Having one or more prior pregnancies increased the risk
      for monozygotic twinning among day 5-6 transfers (adjusted RR 1.26, 95% CI 1.03
      1.53). CONCLUSION: Monozygotic twinning after single embryo transfers was more
      common among day 5-6 embryo transfers than day 2-3 transfers. Use of assisted
      hatching was associated with increased risk for monozygotic twinning for day 2-3
      transfers. LEVEL OF EVIDENCE: II.

PMID- 25560113
TI  - The North American Fetal Therapy Network consensus statement: prenatal
      surveillance of uncomplicated monochorionic gestations.
AB  - Because they share a common placenta, monochorionic gestations are subject to
      unique pregnancy complications that can threaten the life and health of both
      fetuses and therefore impose a disproportionate disease burden on overall
      perinatal morbidity and mortality. Early detection of these unique disease
      processes may allow for prompt referral to a regional treatment center,
      comprehensive counseling, and better patient outcomes. The North American Fetal
      Therapy Network is a consortium of 30 medical institutions in the United States
      and Canada with established expertise in fetal surgery and other forms of
      multidisciplinary care for complex fetal disorders. The goal of this publication
      is to briefly describe complications of monochorionic gestations and to provide
      multidisciplinary, evidence-based, and consensus-driven recommendations for
      surveillance of uncomplicated monochorionic gestations.

PMID- 25560114
TI  - Hypertensive disorders and pregnancy-related stroke: frequency, trends, risk
      factors, and outcomes.
AB  - OBJECTIVE: To evaluate trends and associations of hypertensive disorders of
      pregnancy with stroke risk and test the hypothesis that hypertensive disorders of
      pregnancy-associated stroke results in higher rates of stroke-related
      complications than pregnancy-associated stroke without hypertensive disorders.
      METHODS: A cross-sectional study was performed using 81,983,216 pregnancy
      hospitalizations from the 1994-2011 Nationwide Inpatient Sample. Rates of stroke
      hospitalizations with and without these hypertensive disorders were reported per
      10,000 pregnancy hospitalizations. Using logistic regression, adjusted odds
      ratios (OR) with 95% confidence intervals were obtained. RESULTS: Between 1994
      1995 and 2010-2011, the nationwide rate of stroke with hypertensive disorders of
      pregnancy increased from 0.8 to 1.6 per 10,000 pregnancy hospitalizations (103%),
      whereas the rate without these disorders increased from 2.2 to 3.2 per 10,000
      pregnancy hospitalizations (47%). Women with hypertensive disorders of pregnancy
      were 5.2 times more likely to have a stroke than those without. Having
      traditional stroke risk factors (eg, congenital heart disease, atrial
      fibrillation, sickle cell anemia, congenital coagulation defects) substantially
      increased the stroke risk among hypertensive disorders of pregnancy
      hospitalizations: from adjusted OR 2.68 for congenital coagulation defects to
      adjusted OR 13.1 for congenital heart disease. Stroke-related complications were
      increased in stroke with hypertensive disorders of pregnancy compared with
      without (from adjusted OR 1.23 for nonroutine discharge to adjusted OR 1.93 for
      mechanical ventilation). CONCLUSION: Having traditional stroke risk factors
      substantially increased the stroke risk among hypertensive disorders of pregnancy
      hospitalizations. Stroke with hypertensive disorders in pregnancy had two
      distinctive characteristics: a greater increase in frequency since the mid-1990s
      and significantly higher stroke-related complication rates. LEVEL OF EVIDENCE:
      III.

PMID- 25560116
TI  - Postpartum weight retention risk factors and relationship to obesity at 1 year.
AB  - OBJECTIVE: To explore risk factors for postpartum weight retention at 1 year
      after delivery in predominantly low-income women. METHODS: Data were collected
      from 774 women with complete height and weight information from participants in
      the Eunice Kennedy Shriver National Institute of Child Health and Human
      Development Community Child Health Network, a national five-site, prospective
      cohort study. Participants were enrolled primarily in the hospitals immediately
      after delivery. Maternal interviews conducted at 1, 6, and 12 months postpartum
      identified risk factors for weight retention and included direct measurement of
      height and weight at 6 and 12 months. Logistic regression assessed the
      independent contribution of postpartum weight retention on obesity. RESULTS:
      Women had a mean prepregnancy weight of 161.5 lbs (body mass index [BMI] 27.7).
      Women gained a mean of 32 lbs while pregnant and had a 1-year mean postpartum
      weight of 172.6 lbs (BMI 29.4). Approximately 75% of women were heavier 1 year
      postpartum than they were prepregnancy, including 47.4% retaining more than 10
      lbs and 24.2% more than 20 lbs. Women retaining at least 20 lbs were more often
      African American, younger, poor, less educated, or on pubic insurance. Race and
      socioeconomic disparities were associated with high prepregnancy BMI and
      excessive weight gain during pregnancy, associations that were attenuated by
      breastfeeding at 6 months and moderate exercise. Of the 39.8 with normal
      prepregnancy BMI, one third became overweight or obese 1 year postpartum.
      CONCLUSION: Postpartum weight retention is a significant contributor to the risk
      for obesity 1 year postpartum, including for women of normal weight prepregnancy.
      Postpartum, potentially modifiable behaviors may lower the risk. LEVEL OF
      EVIDENCE: III.

PMID- 25560117
TI  - Obstetric balloon for treatment of foreshortened vagina using the McIndoe
      technique.
AB  - BACKGROUND: When conservative options such as the use of vaginal dilators fail,
      the McIndoe technique may be used in the surgical treatment of a foreshortened
      vagina. The McIndoe procedure, an approach commonly used for the treatment of
      vaginal agenesis, requires a mold over which a skin graft is sutured and placed
      inside the vagina. In most surgical descriptions, this mold is made from non
      sterile foam, condoms, or gloves. Because makeshift molds can no longer be used
      in operating rooms owing to strict regulations, alternative methods must be
      employed. INSTRUMENT: The obstetric balloon is a good choice for use as a soft
      and adjustable vaginal mold for a modified McIndoe procedure because it is
      readily available as an approved device in hospitals that provide obstetric
      services. EXPERIENCE: This technique was successfully employed in a 54-year-old
      woman to treat foreshortened vagina. CONCLUSION: An obstetric balloon can be used
      effectively as a mold for vaginal reconstruction with the McIndoe technique.

PMID- 25560118
TI  - Uterine didelphys and vaginal birth after cesarean delivery.
AB  - BACKGROUND: Mullerian anomalies are associated with adverse pregnancy outcomes.
      We discuss pregnancy in anomalous uteri, with a focus on uterine didelphys, in
      the setting of a prior cesarean delivery. CASE(S): A 30-year-old woman, gravida 2
      para 1001, presented in latent labor at 40 1/7 weeks of gestation. Her first
      pregnancy was in the right horn of a didelphic uterus and resulted in a cesarean
      delivery in the setting of chorioamnionitis remote from delivery. The current
      pregnancy was in the left horn and resulted in a vacuum-assisted vaginal delivery
      after spontaneous labor. CONCLUSION: There is sparse literature on a trial of
      labor after cesarean delivery in a uterine didelphys.

PMID- 25560115
TI  - Risk of adverse pregnancy outcomes by prepregnancy body mass index: a population
      based study to inform prepregnancy weight loss counseling.
AB  - OBJECTIVE: To estimate the absolute risks of adverse maternal and perinatal
      outcomes based on small differences in prepregnancy body mass (eg, 10% of body
      mass or 10-20 pounds). METHODS: This population-based cohort study (N=226,958)
      was drawn from all singleton pregnancies in British Columbia (Canada) from 2004
      to 2012. The relationships between prepregnancy body mass index (BMI) (as a
      continuous, nonlinear variable) and adverse pregnancy outcomes were examined
      using logistic regression models. Analyses were adjusted for maternal age,
      height, parity, and smoking in pregnancy. Adjusted absolute risks of each outcome
      are reported according to incremental differences in prepregnancy BMI and weight
      in pounds. RESULTS: A 10% difference in prepregnancy BMI was associated with at
      least a 10% lower risk of preeclampsia, gestational diabetes, indicated preterm
      delivery, macrosomia, and stillbirth. In contrast, larger differences in
      prepregnancy BMI (20-30% differences in BMI) were necessary to meaningfully
      reduce risks of cesarean delivery, shoulder dystocia, neonatal intensive care
      unit stay 48 hours or longer, and in-hospital newborn mortality. Prepregnancy BMI
      was not associated with risk of postpartum hemorrhage requiring intervention,
      severe maternal morbidity or maternal mortality, or spontaneous preterm delivery
      before 32 weeks of gestation. CONCLUSION: These results can inform prepregnancy
      weight loss counseling by defining achievable weight loss goals for patients that
      may reduce their risk of poor perinatal outcomes. LEVEL OF EVIDENCE: II.

PMID- 25560119
TI  - What is new in stillbirth?: important recent articles.
AB  - This month we focus on current research in stillbirth. Dr. Andrews discusses five
      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- 25560120
TI  - Medicaid pregnancy termination funding and racial disparities in congenital
      anomaly-related infant deaths.
AB  - OBJECTIVE: To explore whether state restrictions on Medicaid funding for
      pregnancy termination of anomalous fetuses could be contributing to the black
      white disparity in infant death resulting from congenital anomalies. METHODS:
      Data on deaths resulting from anomalies were obtained from U.S. vital statistics
      records (1983-2004) and the Nationwide Inpatient Sample (2003-2007). We conducted
      an ecological study using Poisson and logistic regression to explore the
      association between state Medicaid funding for pregnancy terminations of
      anomalous fetuses and infant death resulting from anomalies by calendar time,
      race, and individual Medicaid status. RESULTS: Since 1983, a gap in anomaly
      related infant death has developed between states without compared with those
      with Medicaid funding for pregnancy termination (rate ratio in 2004 1.21, 95%
      confidence interval [CI] 1.18-1.24; crude risks: 146.8 compared with
      121.7/100,000). Blacks were significantly more likely than whites to be on
      Medicaid (60.2% compared with 29.2%) and to live in a state without Medicaid
      funding for pregnancy termination (65.8% compared with 59.6%). The increased risk
      of anomaly-related death associated with lack of state Medicaid funding for
      pregnancy termination was most pronounced among black women on Medicaid (relative
      risk 1.94, 95% CI 1.52-2.36; crude risks: 245.5 compared with 129.3/100,000).
      CONCLUSION: States without Medicaid funding for pregnancy termination of
      anomalous fetuses have higher rates of infant death resulting from anomalies than
      those with funding, and this difference is most pronounced among black women on
      Medicaid. Restrictions on Medicaid funding for termination of anomalous fetuses
      potentially could be contributing to the black-white disparity in anomaly-related
      infant death. LEVEL OF EVIDENCE: II.

PMID- 25560121
TI  - Association between the New Hampshire parental notification law and minors
      undergoing abortions in northern New England.
AB  - OBJECTIVE: To assess the association of the 2012 New Hampshire parental
      notification law with patterns of abortion in northern New England minors.
      METHODS: This was a retrospective cohort study examining all minors undergoing
      abortions at Planned Parenthood clinics in Vermont, New Hampshire, and Maine from
      2011 to 2012. RESULTS: The number of abortions among minors in New Hampshire
      decreased from 95 to 50 (47%, 95% confidence interval [CI] 37.03-57.88; P=.015)
      from 2011 to 2012. Minors residing in Massachusetts, which has a parental consent
      law, accounted for 62% of this change. Abortions among New Hampshire minors
      decreased by 19% (from 57 to 46, 95% CI 10.05-31.91; P=.707), and minors did not
      seek more abortions at Planned Parenthood clinics in Vermont or Maine. The
      average age, gestational age, and number of second-trimester cases did not
      change. Parental awareness of the abortion increased from 2011 to 2012 in New
      Hampshire (54%, 95% CI 44.21-63.96 to 92%, 95% CI 80.65-97.36; P<.001); however,
      there was no difference in the overall rate of adult involvement during the study
      period. Four (8%) minors in New Hampshire used the judicial bypass option.
      CONCLUSION: Implementation of the New Hampshire parental notification law
      correlated with a decrease in minors undergoing abortions at Planned Parenthood
      clinics in the state, largely as a result of a decrease in the number of minors
      coming from Massachusetts. There was an increase in parental involvement but no
      change in overall adult involvement, and use of the judicial bypass option or
      minors crossing state lines was uncommon.

PMID- 25560122
TI  - Incidence of emergency department visits and complications after abortion.
AB  - OBJECTIVE: To conduct a retrospective observational cohort study to estimate the
      abortion complication rate, including those diagnosed or treated at emergency
      departments (EDs). METHODS: Using 2009-2010 abortion data among women covered by
      the fee-for-service California Medicaid program and all subsequent health care
      for 6 weeks after having an abortion, we analyzed reasons for ED visits and
      estimated the abortion-related complication rate and the adjusted relative risk.
      Complications were defined as receiving an abortion-related diagnosis or
      treatment at any source of care within 6 weeks after an abortion. Major
      complications were defined as requiring hospital admission, surgery, or blood
      transfusion. RESULTS: A total of 54,911 abortions among 50,273 fee-for-service
      Medi-Cal beneficiaries were identified. Among all abortions, 1 of 16 (6.4%,
      n=3,531) was followed by an ED visit within 6 weeks but only 1 of 115 (0.87%,
      n=478) resulted in an ED visit for an abortion-related complication.
      Approximately 1 of 5,491 (0.03%, n=15) involved ambulance transfers to EDs on the
      day of the abortion. The major complication rate was 0.23% (n=126, 1/436): 0.31%
      (n=35) for medication abortion, 0.16% (n=57) for first-trimester aspiration
      abortion, and 0.41% (n=34) for second-trimester or later procedures. The total
      abortion-related complication rate including all sources of care including EDs
      and the original abortion facility was 2.1% (n=1,156): 5.2% (n=588) for
      medication abortion, 1.3% (n=438) for first-trimester aspiration abortion, and
      1.5% (n=130) for second-trimester or later procedures. CONCLUSION: Abortion
      complication rates are comparable to previously published rates even when ED
      visits are included and there is no loss to follow-up. LEVEL OF EVIDENCE: II.

PMID- 25560123
TI  - Pregnancy and severe influenza infection in the 2013-2014 influenza season.
AB  - OBJECTIVE: To describe the epidemiologic and clinical characteristics of
      critically ill pregnant and postpartum women with influenza infection reported in
      the 2013-2014 season. METHODS: The California Department of Public Health
      conducts surveillance for patients with laboratory-confirmed influenza who die or
      require hospitalization in intensive care units. For this case series, we
      reviewed data on pregnant and postpartum (6 weeks or less from delivery) women
      reported in the 2013-2014 influenza season. RESULTS: From September 29, 2013,
      through May 17, 2014, 17 pregnant women with severe influenza were reported. The
      median age was 29 years (range 17-44 years). Sixteen (94%) were in the second or
      third trimester. Fifteen (88%) patients were hospitalized, nine (53%) required
      mechanical ventilation, five (29%) required emergent cesarean delivery, and four
      (24%) died. Of 14 patients with available information, only two (14%) received
      influenza vaccination during pregnancy. Seven patients who tested positive by
      polymerase chain reaction also had rapid influenza diagnostic testing performed;
      only one (14%) had a positive rapid influenza diagnostic test results. Fifteen
      patients received antiviral treatment; four (27%) began treatment within 48 hours
      of symptom onset. One additional patient was 36 days postpartum and required
      intensive care unit admission and mechanical ventilation for influenza-associated
      acute respiratory distress syndrome. CONCLUSION: Influenza remains a significant
      cause of morbidity and mortality in pregnant and postpartum women; in our series,
      a majority were not vaccinated. During the influenza season, pregnant women with
      suspected influenza should receive prompt empiric antiviral therapy, regardless
      of rapid influenza diagnostic test results or vaccination status. LEVEL OF
      EVIDENCE: III.

PMID- 25560124
TI  - Human immunodeficiency virus-associated pulmonary arterial hypertension diagnosed
      postpartum.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) is a significant risk factor for
      pulmonary arterial hypertension. There is a significant added risk for maternal
      mortality when superimposed on the physiologic changes of pregnancy. CASE: A 37
      year-old HIV-positive woman underwent caesarean delivery at 27 weeks of gestation
      for chorioamnionitis and malpresentation after premature rupture of membranes.
      Postpartum, she was diagnosed with HIV-associated pulmonary arterial
      hypertension, which was managed successfully with sildenafil and ambrisentan.
      CONCLUSION: Pulmonary arterial hypertension associated with HIV is a life
      threatening complication that may occur in pregnant women with HIV. The rarity of
      the condition, overlapping with symptoms commonly seen in pregnancy, and its
      broad differential diagnosis may confound the diagnosis. Prompt recognition and
      therapy are required to optimize clinical outcomes.

PMID- 25560125
TI  - Use of granulocyte colony-stimulating factor during pregnancy in women with
      chronic neutropenia.
AB  - OBJECTIVE: To report outcomes associated with the administration of granulocyte
      colony-stimulating factor (G-CSF) to women with chronic neutropenia during
      pregnancy. METHODS: We conducted an observational study of women of childbearing
      potential with congenital, cyclic, idiopathic, or autoimmune neutropenia enrolled
      in the Severe Chronic Neutropenia International Registry to determine outcomes of
      pregnancies, without and with chronic G-CSF therapy, 1999-2014. Treatment
      decisions were made by the patients' personal physicians. A research nurse
      conducted telephone interviews of all enrolled U.S. women of childbearing
      potential using a standard questionnaire. Comparisons used Fisher's exact test
      analysis and Student's t test. RESULTS: One hundred seven women reported 224
      pregnancies, 124 without G-CSF therapy and 100 on chronic G-CSF therapy (median
      dose 1.0 micrograms/kg per day, range 0.02-8.6 micrograms/kg per day). There were
      no significant differences in adverse events between the groups considering all
      pregnancies or individual mothers, for example, spontaneous terminations (all
      pregnancies: no G-CSF in 27/124, G-CSF in 13/100; P=.11, Fisher's exact test),
      preterm labors (all pregnancies, no G-CSF in 9/124, G-CSF in 2/100, P=.12). A
      study with at least 300 per group would be needed to detect a difference in these
      events with 80% statistical power (alpha=0.05). Four newborns of mothers with
      idiopathic or autoimmune neutropenia not on G-CSF (4/101) had life-threatening
      infections, whereas there were no similar events (0/90) in the treated group, but
      this difference was also not statistically significant (P=.124). Adverse events
      in the neonates were similar for the two groups. CONCLUSION: This observational
      study showed no significant adverse effects of administration of G-CSF to women
      with severe chronic neutropenia during pregnancy. LEVEL OF EVIDENCE: III.

PMID- 25560126
TI  - Use of complementary and alternative medicines during the third trimester.
AB  - OBJECTIVE: To estimate the prevalence, indications, and associated factors for
      complementary and alternative medicine use during the last trimester of
      pregnancy. METHODS: A questionnaire survey was conducted of women with a live
      birth (N=700) admitted to the postnatal unit at the Royal Aberdeen Maternity
      Hospital, northeast Scotland. Outcome measures included: complementary and
      alternative medicine used; vitamins and minerals used; reasons for complementary
      and alternative medicine use; independent associated factors for use; views; and
      experiences. Descriptive and inferential statistical analysis was performed.
      RESULTS: The response rate was 79.6% of eligible women. Two thirds of respondents
      (61.4%) reported using complementary and alternative medicine, excluding vitamins
      and minerals, during the third trimester. Respondents reported using a total of
      30 different complementary and alternative medicine modalities, of which oral
      herbal products were the most common (38% of respondents, 40 different products).
      The independent associated factors for complementary and alternative medicine use
      identified were: complementary and alternative medicine use before pregnancy
      (odds ratio [OR] 4.36, 95% confidence interval [CI] 2.39-7.95, P<.001); a
      university education (OR 2.41, 95% CI 1.46-4.0, P=.001), and complementary and
      alternative medicine use by family or friends (OR 2.36, 95% CI 1.61-3.47,
      P<.001). There was no association with health care professional recommendations.
      Users were significantly more likely than nonusers to agree that complementary
      and alternative medicines were safer than prescribed medicines (P=.006), less
      likely to be associated with side effects (P<=.001), and could interfere with
      conventional medicines (P<=.001). CONCLUSION: Despite the majority of
      respondents, and notably users, being uncertain about their safety and
      effectiveness, complementary and alternative medicine modalities and
      complementary and alternative medicine products are widely used during the third
      trimester of pregnancy in this study population. Although prior use was the most
      significant independent associated factor, the role of family and friends, rather
      than health professionals, in the decision to use complementary and alternative
      medicine may be of concern. LEVEL OF EVIDENCE: III.

PMID- 25560128
TI  - Prenatal management of monoamniotic twin pregnancies.

PMID- 25560127
TI  - Vaccinations for pregnant women.
AB  - In the United States, eradication and reduction of vaccine-preventable diseases
      through immunization has directly increased life expectancy by reducing
      mortality. Although immunization is a public priority, vaccine coverage among
      adult Americans is inadequate. The Institute of Medicine, the Community
      Preventive Services Task Force, and other public health entities have called for
      the development of innovative programs to incorporate adult vaccination into
      routine clinical practice. Obstetrician-gynecologists are well suited to serve as
      vaccinators of women in general and more specifically pregnant women. Pregnant
      women are at risk for vaccine-preventable disease-related morbidity and mortality
      and adverse pregnancy outcomes, including congenital anomalies, spontaneous
      abortion, preterm birth, and low birth weight. In addition to providing direct
      maternal benefit, vaccination during pregnancy likely provides direct fetal and
      neonatal benefit through passive immunity (transplacental transfer of maternal
      vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2)
      vaccines specifically recommended during pregnancy and postpartum; 3) vaccines
      recommended during pregnancy and postpartum based on risk factors and special
      circumstances; 4) vaccines currently under research and development for licensure
      for maternal-fetal immunization; and 5) barriers to maternal immunization and
      available patient and health care provider resources.

PMID- 25560129
TI  - Prenatal management of monoamniotic twin pregnancies.

PMID- 25560130
TI  - In reply.

PMID- 25560131
TI  - Contained power morcellation within an insufflated isolation bag.

PMID- 25560132
TI  - In reply.

PMID- 25560133
TI  - Treatment of vaginal cuff evisceration.

PMID- 25560134
TI  - In reply.

PMID- 25560140
TI  - Committee opinion no. 615: Access to contraception.
AB  - Nearly all U.S. women who have ever had sexual intercourse have used some form of
      contraception at some point during their reproductive lives. However, multiple
      barriers prevent women from obtaining contraceptives or using them effectively
      and consistently. All women should have unhindered and affordable access to all
      U.S. Food and Drug Administration-approved contraceptives. This Committee Opinion
      reviews barriers to contraceptive access and offers strategies to improve access.

PMID- 25560141
TI  - Committee opinion no. 616: Newborn screening and the role of the obstetrician
      gynecologist.
AB  - Newborn screening is a mandatory state-based public health program that provides
      all newborns in the United States with presymptomatic testing and necessary
      follow-up health care for a variety of medical conditions. The goal of this
      essential public health program is to decrease morbidity and mortality by
      screening for disorders in which early intervention will improve neonatal and
      long-term health outcomes. The results of surveys and focus groups of expectant
      parents demonstrate that women and their families would like to receive
      information about newborn screening during their prenatal care visits. Providing
      newborn screening information during prenatal care visits can be accomplished in
      a number of ways and should be adapted to individual practice style.

PMID- 25560142
TI  - Committee opinion no. 617: End-of-life decision making.
AB  - Obstetrician-gynecologists care for women throughout their lifespans and are in
      an ideal position to have ongoing discussions with healthy patients about their
      values and wishes regarding future care and to encourage them to complete an
      advance directive for health care. In addition, situations may arise in which
      obstetrician-gynecologists need to participate in end-of-life care. When end-of
      life decisions need to be made while a woman is pregnant, the level of ethical
      complexity often is increased. The purpose of this Committee Opinion is to
      discuss ethical issues related to end-of-life care, historical and legal
      constructs, patient-physician communication, intradisciplinary and
      interdisciplinary collaboration, and educational opportunities pertinent to
      obstetrician-gynecologists and other providers of women's health care.

PMID- 25560143
TI  - Committee opinion no. 618: Ovarian reserve testing.
AB  - The main goal of ovarian reserve testing is to identify those individuals who are
      at risk of decreased or diminished ovarian reserve, commonly known as DOR.
      Although ovarian reserve testing cannot predict the end of one's reproductive
      years, results outside the range expected for a patient's age can encourage the
      individual to pursue more aggressive treatment options to achieve pregnancy.
      Ovarian reserve testing should be performed for women older than 35 years who
      have not conceived after 6 months of attempting pregnancy and women at higher
      risk of diminished ovarian reserve. When test results suggest decreased or
      diminished ovarian reserve, if appropriate, an infertility evaluation should be
      initiated. It is reasonable to counsel the woman that her window of opportunity
      to conceive may be shorter than anticipated, and attempting to conceive sooner
      rather than later is encouraged. Compared with women of similar age, women with
      diminished ovarian reserve commonly have regular menses but a reduced quantity of
      ovarian follicles and, thus, may have a limited response to ovarian stimulation
      with fertility medications and reduced fecundity (probability of achieving a live
      birth in a single reproductive cycle). At this time, ovarian reserve testing
      results cannot be extrapolated to predict the likelihood of spontaneous
      conception.

PMID- 25560144
TI  - Committee opinion no. 619: Gynecologic surgery in the obese woman.
AB  - Obesity is a serious problem worldwide and particularly in the United States, and
      in women is associated with an increased risk of death and morbid conditions
      (including hypertension, diabetes mellitus, obstructive sleep apnea, and
      hypercholesterolemia) as well as malignancies such as endometrial and
      postmenopausal breast cancer. Adverse effects after gynecologic surgery, such as
      surgical site infection, venous thromboembolism, and wound complications, are
      more prevalent in obese women than in normal-weight women. Preoperative
      consultation with an anesthesiologist should be considered for the obese patient
      in whom the possibility of obstructive sleep apnea is suspected on clinical
      grounds or who is at risk of coronary artery disease, has a difficult airway, or
      has poorly controlled hypertension. Gynecologic surgeons should have the
      knowledge to counsel obese women on the risks specific to this group. As with all
      patients, evidence demonstrates that, in general, vaginal hysterectomy is
      associated with better outcomes and fewer complications than laparoscopic or
      abdominal hysterectomy. Postoperative care of the obese patient is similar to
      postoperative care of the normalweight patient and comorbid conditions should be
      taken into consideration.

PMID- 25560145
TI  - Committee opinion no. 620: Salpingectomy for ovarian cancer prevention.
AB  - Ovarian cancer has the highest mortality rate out of all types of gynecologic
      cancer and is the fifth leading cause of cancer deaths among women. Current
      attempts at screening for ovarian cancer have been unsuccessful and are
      associated with false-positive test results that lead to unnecessary surgery and
      surgical complications. Prophylactic salpingectomy may offer clinicians the
      opportunity to prevent ovarian cancer in their patients. Randomized controlled
      trials are needed to support the validity of this approach to reduce the
      incidence of ovarian cancer. The approach to hysterectomy or sterilization should
      not be influenced by the theoretical benefit of salpingectomy. Surgeons should
      continue to observe and practice minimally invasive techniques.

PMID- 25560146
TI  - Committee opinion no. 621: Patient safety and health information technology.
AB  - The advantages of health information technology (IT) include facilitating
      communication between health care providers; improving medication safety,
      tracking, and reporting; and promoting quality of care through optimized access
      to and adherence to guidelines. Health IT systems permit the collection of data
      for use for quality management, outcome reporting, and public health disease
      surveillance and reporting. However, improvement is needed with all health IT,
      especially regarding design, implementation, and integration between platforms
      within the work environment. Robust interoperability is critical for safe care,
      but this goal has proved elusive. Significant patient safety concerns already
      have been recognized; it is important to keep patient safety and quality as the
      primary focus.

PMID- 25560148
TI  - Overexpression of zinc-finger protein 777 (ZNF777) inhibits proliferation at low
      cell density through down-regulation of FAM129A.
AB  - Kruppel-associated box-containing zinc finger proteins (KRAB-ZFPs) regulate a
      wide range of cellular processes. KRAB-ZFPs have a KRAB domain, which binds to
      transcriptional corepressors, and a zinc finger domain, which binds to DNA to
      activate or repress gene transcription. Here, we characterize ZNF777, a member of
      KRAB-ZFPs. We show that ZNF777 localizes to the nucleus and inducible
      overexpression of ZNF777 inhibits cell proliferation in a manner dependent on its
      zinc finger domain but independent of its KRAB domain. Intriguingly, ZNF777
      overexpression drastically inhibits cell proliferation at low cell density but
      slightly inhibits cell proliferation at high cell density. Furthermore, ZNF777
      overexpression decreases the mRNA level of FAM129A irrespective of cell density.
      Importantly, the protein level of FAM129A strongly decreases at low cell density,
      but at high cell density the protein level of FAM129A does not decrease to that
      observed at low cell density. ZNF777-mediated inhibition of cell proliferation is
      attenuated by overexpression of FAM129A at low cell density. Furthermore, ZNF777
      mediated down-regulation of FAM129A induces moderate levels of the cyclin
      dependent kinase inhibitor p21. These results suggest that ZNF777 overexpression
      inhibits cell proliferation at low cell density and that p21 induction by ZNF777
      mediated down-regulation of FAM129A plays a role in inhibition of cell
      proliferation.

PMID- 25560147
TI  - Quality control mechanisms in cellular and systemic DNA damage responses.
AB  - The maintenance of the genome is of pivotal importance for the functional
      integrity of cells and tissues. The gradual accumulation of DNA damage is thought
      to contribute to the functional decline of tissues and organs with ageing.
      Defects in multiple genome maintenance systems cause human disorders
      characterized by cancer susceptibility, developmental failure, and premature
      ageing. The complex pathological consequences of genome instability are
      insufficiently explained by cell-autonomous DNA damage responses (DDR) alone.
      Quality control pathways play an important role in DNA repair and cellular DDR
      pathways. Recent years have revealed non-cell autonomous effects of DNA damage
      that impact the physiological adaptations during ageing. We will discuss the role
      of quality assurance pathways in cell-autonomous and systemic responses to genome
      instability. 

PMID- 25560150
TI  - Two birds, one stone approach, integrated action plan for pneumonia and diarrhea.

PMID- 25560149
TI  - RNA-Seq profiling of single bovine oocyte transcript abundance and its modulation
      by cytoplasmic polyadenylation.
AB  - Molecular changes occurring during mammalian oocyte maturation are partly
      regulated by cytoplasmic polyadenylation (CP) and affect oocyte quality, yet the
      extent of CP activity during oocyte maturation remains unknown. Single bovine
      oocyte RNA sequencing (RNA-Seq) was performed to examine changes in transcript
      abundance during in vitro oocyte maturation in cattle. Polyadenylated RNA from
      individual germinal-vesicle and metaphase-II oocytes was amplified and processed
      for Illumina sequencing, producing approximately 30 million reads per replicate
      for each sample type. A total of 10,494 genes were found to be expressed, of
      which 2,455 were differentially expressed (adjusted P < 0.05 and fold change >2)
      between stages, with 503 and 1,952 genes respectively increasing and decreasing
      in abundance. Differentially expressed genes with complete 3'-untranslated-region
      sequence (279 increasing and 918 decreasing in polyadenylated transcript
      abundance) were examined for the presence, position, and distribution of motifs
      mediating CP, revealing enrichment (85%) and lack thereof (18%) in up- and down
      regulated genes, respectively. Examination of total and polyadenylated RNA
      abundance by quantitative PCR validated these RNA-Seq findings. The observed
      increases in polyadenylated transcript abundance within the RNA-Seq data are
      likely due to CP, providing novel insight into targeted transcripts and resultant
      differential gene expression profiles that contribute to oocyte maturation.

PMID- 25560151
TI  - Prenatal screening: perspective for the pediatrician.
AB  - Pediatricians are the first contact of a child with genetic disorders such as
      Down Syndrome. After diagnosis, parents often express and wish that if it was
      possible to detect it during pregnancy and could it be avoided in the future
      pregnancy. This makes it essential that pediatricians should have some idea about
      the basic screening methods and strategy used during pregnancy. 

PMID- 25560152
TI  - Choice of maintenance fluids - does it hold water?

PMID- 25560153
TI  - Isn't it time to stop using 0.18% saline in dextrose solutions for intravenous
      maintenance fluid therapy in children?

PMID- 25560154
TI  - Changes in preterm breast milk composition with advancing infant age.

PMID- 25560155
TI  - Safety and efficacy of isotonic (0.9%) vs. hypotonic (0.18%) saline as
      maintenance intravenous fluids in children: a randomized controlled trial.
AB  - OBJECTIVE: To compare the safety and efficacy of isotonic versus hypotonic
      maintenance fluid in children. DESIGN: Randomized controlled trial. SETTING:
      Tertiary-level teaching hospital. PARTICIPANTS: 60 children (age 0.5 to 12 years)
      who were admitted and anticipated to receive intravenous fluid for the next 48
      hours. INTERVENTION: Hypotonic fluid (Standard maintenance volume as 0.18% NaCl
      in 5% dextrose) or Isotonic fluid (60% Standard maintenance volume as 0.9% NaCl
      solution in 5% dextrose). OUTCOME MEASURES: Primary: Incidence of hyponatremia.
      Secondary: Serum sodium, serum osmolality, blood sugar, blood urea, serum
      creatinine, serum potassium, serum chloride, pH, urine output, change in weight,
      morbidity and death. RESULTS: At 24 hours, hyponatremia was noted in 7 (24%)
      patients in the isotonic and 16 (55%) in hypotonic group (P=0.031). At 48 hours,
      hyponatremia was noted in 4 (14%) and 13 (45%) patients in isotonic and hypotonic
      group, respectively (P=0.02). There was significant change in sodium levels in
      both isotonic (P=0.036) and hypotonic (P<0.001) intervention groups. The peak
      fall in mean serum sodium level was noted at 24 hours (-6.5, 95%CI: -3.5, -9.6
      mEq/L; P<0.001) in hypotonic group. In isotonic group, there was significant
      increase between 24 and 48 hours (4.3, 95% CI: 0.1, 8.4 mEq/L; P=0.04).
      CONCLUSIONS: Reduced volume isotonic fluid results in fewer episodes of
      hyponatremia than hypotonic fluid in sick children during the first 48 hours of
      intravenous fluid therapy.

PMID- 25560156
TI  - Consensus guidelines on management of childhood convulsive status epilepticus.
AB  - JUSTIFICATION: Status epilepticus has a wide etiological spectrum, and
      significant morbidity and mortality. Management using a pre-determined uniform
      protocol leads to better outcomes. Multiple protocols for management of childhood
      status epilepticus are available, without much consensus. PROCESS: A 'Multi
      disciplinary Consensus Development Workshop on Management of Status Epilepticus
      in Children in India' was organized. The invited experts included Pediatricians,
      Pediatric neurologists, Neurologists, Epileptologists, and Pediatric intensive
      care specialists from India, with experience in the relevant field. Experts had
      previously been divided into focus groups and had interacted on telephone and e
      mail regarding their group recommendations, and developed consensus on the topic.
      During the meeting, each group presented their recommendations, which were
      deliberated upon by the house and a consensus was reached on various issues; the
      document was finalized after incorporating suggestions of experts on the draft
      document. OBJECTIVE: To provide consensus guidelines on evaluation and management
      of convulsive status epilepticus in children in India (excluding neonatal and
      super-refractory status epilepticus). RECOMMENDATIONS: Each institution should
      use a pre-determined protocol for management of status epilepticus; pre-hospital
      management and early stabilization is the key to a satisfactory outcome of status
      epilepticus. Pharmacotherapy should not be delayed for any investigations; the
      initial management should consist of a parenteral benzodiazepine by any route
      feasible. Subsequent management has been detailed. The group also felt the need
      for more epidemiological research on status epilepticus from India, and
      identified certain research areas for the purpose.

PMID- 25560157
TI  - Parenting in children and adolescents with psychosis.
AB  - NEED AND PURPOSE OF REVIEW: Psychotic symptoms appear in children and adolescents
      in the most crucial years, during the individual's career development. The
      challenges faced by parents of psychotic children are in dealing with their
      disruptive behaviours, negative symptoms, cognitive deficits, delusions and
      hallucinations. This paper presents an overview of the childhood psychosis and
      how parenting can be done effectively for this population. METHODS: Articles were
      retrieved from the Medline, Cochrane database, Google Scholar, Medscape; using
      the search terms 'parenting and childhood psychosis', and 'childhood psychoses;
      and standard textbooks were consulted. MAIN CONCLUSIONS: Educating parents how to
      recognize early symptoms, explaining treatment adherence, side effects of
      medications along with non-pharmacological measures like dealing with expressed
      emotions, lowering expectations, enhancing social supports, healthy lifestyle,
      and making patients independent. Awareness, early identification and effective
      parenting for psychosis may help bridge the wide gap between scarce skilled
      mental health professionals, inefficient resources and large paediatric
      population.

PMID- 25560158
TI  - Changes in preterm human milk composition with particular reference to
      introduction of mixed feeding.
AB  - OBJECTIVE: To study the changes in composition of preterm milk till 6 months of
      age. METHODS: Milk samples from 33, 19, 7 and 12 lactating mothers (delivered <34
      weeks) were analyzed on days 7, 28, 90 and 180, respectively. RESULTS:
      Triglyceride and sodium concentrations increased significantly with time and
      protein concentration decreased significantly over 180 days. Sodium (P=0.02) and
      triglyceride concentrations (P=0.06) were higher in milk samples of mothers who
      had introduced mixed feeding by 6 months post natal age (n=6) compared to
      exclusively breast-feeding mothers (n=6); but lactose and protein content was not
      significantly different. CONCLUSIONS: Milk of preterm mothers has higher amount
      of triglycerides and sodium during introduction of mixed feeding.

PMID- 25560159
TI  - Immunoglobulin levels and CD4 / CD8 counts in beta- thalassemia major.
AB  - OBJECTIVE: This cross-sectional study determined the CD4, CD8 counts and serum
      immunoglobulins in transfusion dependent b - thalassemic patients, and correlated
      them with anti-HIV, anti-HCV and HBsAg status, number of transfusions, iron
      overload and splenectomy. METHODS: Patients with acute or chronic diseases
      (except HIV, Hepatitis B and C), on immunosuppressive drugs or vaccinated within
      one month prior to study were excluded. CD4, CD8 counts and serum Immunoglobulins
      were documented. RESULTS: Increasing transfusions led to higher IgA and IgM as
      well as a decline in CD4 and CD8 levels. Higher ferritin correlated with high
      IgM. CD4, CD8 and IgA were significantly higher in splenectomized subjects. HCV
      correlated significantly with lower IgA values. CONCLUSION: Higher transfusion
      requirement, iron overload, splenectomy and HCV infection correlated with
      alterations in different immunological parameters.

PMID- 25560160
TI  - Hematological parameters in adolescents with hyperuricemia.
AB  - OBJECTIVE: To examine the association between hematological indices and serum
      uric acid in adolescents with hyperuricemia. METHODS: 10-year retrospective
      cohort study of 607 patients with hyperuricemia registered with the Pediatric
      Nephrology Department. RESULTS: There was a statistically significant positive
      correlation between serum uric acid levels and BMI Z-scores (r=0.406, P<0.001),
      white and red blood cell counts, hemoglobin and hematocrit. Higher levels of
      hemoglobin, hematocrit and red blood cells were found in adolescents with
      metabolic syndrome than in groups without this condition. CONCLUSION:
      Hematological parameters could be important biological markers of cardiometabolic
      risk in adolescents with hyperuricemia.

PMID- 25560161
TI  - Is Xpert MTB/RIF assay in gastric lavage aspirate useful for diagnosis of smear
      negative childhood pulmonary tuberculosis?

PMID- 25560164
TI  - Waardenburg syndrome presenting with constipation since birth.
AB  - BACKGROUND: Shah-Waardenburg syndrome is Waardenburg syndrome associated with
      Hirschsprung's disease. CASE CHARACTERISTICS: A 10-day-old full-term male neonate
      of Waardenburg syndrome presented with constipation since birth along with
      features of small bowel obstruction. OBSERVATION: Exploratory laparotomy revealed
      distended proximal jejunal and ileal loops along with microcolon; an ileostomy
      was performed. OUTCOME: Postoperatively patient developed sepsis and died.
      Histopathology confirmed total colonic aganglionosis. MESSAGE: Suspect familial
      Shah-Waardenburg syndrome in a neonate of Waardenburg syndrome presenting with
      constipation since birth or intestinal obstruction.

PMID- 25560165
TI  - Wiskott-Aldrich syndrome with macrothrombocytopenia.
AB  - BACKGROUND: Wiskott-Aldrich syndrome is a rare X-linked immunodeficiency disorder
      with a variable phenotype. CASE CHARACTERISTICS: 3.5-year-old boy diagnosed with
      Wiskott-Aldrich syndrome. OBSERVATION: Unusual and persistent thrombocytopenia
      with increased platelet volume (>10fL). He did not exhibit characteristic
      clinical and laboratory finding for the syndrome. OUTCOME: Maternally inherited
      causative mutation in the exon 2 of the WAS gene was disclosed. MESSAGE: This is
      a need for multidisciplinary assessment of patients with congenital or early
      infantile thrombocytopenia, including testing for mutations of the WAS gene in
      all unexplained cases even in the absence of characteristic
      microthrombocytopenia.

PMID- 25560166
TI  - Dextromethorphan: problems with formulations.

PMID- 25560167
TI  - Factitious bleeding disorder in a child: an unusual presentation of Munchausen
      Syndrome.

PMID- 25560168
TI  - Identification of PML/RARa fusion gene by RT-PCR acute promyelocytic leukaemia.

PMID- 25560169
TI  - Vitamin D deficiency: an uncommon cause of quadriparesis.

PMID- 25560170
TI  - Intestinal obstruction due to accidental ingestion of hygroscopic foreign body.

PMID- 25560171
TI  - Indigenously designed meconium aspirator.

PMID- 25560172
TI  - Post kala-azar dermal leishmaniasis: macular variety.

PMID- 25560173
TI  - Examining direct service worker turnover in three long-term care industries in
      Ohio.
AB  - This is the first study to examine direct service worker turnover and its
      predictors across three provider types: nursing homes, home health agencies, and
      providers of services for the developmentally disabled. Stratified random
      sampling procedures were used to select provider types across five geographic
      regions in Ohio. Data were collected from administrative staff. Findings
      indicated that annual direct service worker turnover did not significantly vary
      by provider type (mean = 33%). Predictors of turnover related to job burnout,
      negative social support, and region. Policymakers can promote practices to lower
      direct service worker turnover such as addressing burnout and increasing support.

PMID- 25560174
TI  - Assessment of confirmed urinary tract infection in patients treated with
      dalfampridine for multiple sclerosis.
AB  - Urinary tract infections (UTIs) were reported frequently with dalfampridine
      extended-release (dalfampridine-ER) 10 mg relative to placebo in previous
      multiple sclerosis (MS) studies. The objective of this study was to determine
      whether dalfampridine-ER is associated with increased incidence of confirmed UTIs
      in MS patients. This post hoc analysis used UTI data from a study comparing the 4
      week safety and efficacy of 5 mg (n = 144) and 10 mg (n = 142) twice-daily
      dalfampridine-ER versus placebo (n = 143). To confirm UTIs, three clinical
      assessments were used: standard urinalysis (leukocytes > 5/high-power field);
      urine culture (>= 100,000 and >= 10,000 colony-forming units [CFUs]/mL) for those
      who reported UTIs as adverse events (AEs) or had positive urinalysis; and UTI
      symptomatology. Fisher's exact test assessed statistical significance. The
      proportion of patients who reported UTIs as AEs in the placebo and dalfampridine
      ER 5 mg and 10 mg groups were 5.6%, 6.3%, and 9.9%, respectively. In comparison,
      those with laboratory-confirmed UTIs were lower: >= 100,000 CFUs/mL: 4.2%, 2.8%,
      and 2.8%; and >= 10,000 CFUs/mL: 4.2%, 3.5%, and 4.9%, respectively (no
      significant statistical difference across treatments). The proportion of patients
      with confirmed UTI was similar between dalfampridine-ER and placebo, thus
      suggesting that the treatment does not increase the risk of UTIs.

PMID- 25560176
TI  - Isotopic characterization as a screening tool in authentication of organic
      produce commercially available in western North America.
AB  - The use of nitrogen stable isotopes to discriminate between conventionally and
      organically grown crops has been further developed in this study. Soil and
      irrigation water from different regions, as well as nitrogen fertilizers used,
      have been examined in detail to determine their effects on nitrogen isotope
      composition of spinach, lettuce, broccoli and tomatoes. Over 1000 samples of
      various types of organically and conventionally grown produce of known origin,
      along with the samples of nitrogen fertilizers used for their growth, have been
      analysed in order to assemble the datasets of crop/fertilizer correlations. The
      results demonstrate that the developed approach can be used as a valuable
      component in the verification of agricultural practices for more than 25
      different types of commercially grown green produce, either organic or
      conventional. Over a period of two years, various organic and non-organic greens,
      from different stores in Seattle (WA, USA) and Victoria (BC, Canada), were
      collected and analysed using this methodology with the objective of determining
      any pattern of misrepresentation. 

PMID- 25560175
TI  - Aberrant methylation of imprinted genes is associated with negative hormone
      receptor status in invasive breast cancer.
AB  - Epigenetic regulation of imprinted genes enables monoallelic expression according
      to parental origin, and its disruption is implicated in many cancers and
      developmental disorders. The expression of hormone receptors is significant in
      breast cancer because they are indicators of cancer cell growth rate and
      determine response to endocrine therapies. We investigated the frequency of
      aberrant events and variation in DNA methylation at nine imprinted sites in
      invasive breast cancer and examined the association with estrogen and
      progesterone receptor status. Breast tissue and blood from patients with invasive
      breast cancer (n = 38) and benign breast disease (n = 30) were compared with
      those from healthy individuals (n = 36), matched with the cancer patients by age
      at diagnosis, ethnicity, body mass index, menopausal status and familial history
      of cancer. DNA methylation and allele-specific expression were analyzed by
      pyrosequencing. Tumor-specific methylation changes at IGF2 DMR2 were observed in
      59% of cancer patients, IGF2 DMR0 in 38%, DIRAS3 DMR in 36%, GRB10 ICR in 23%,
      PEG3 DMR in 21%, MEST ICR in 19%, H19 ICR in 18%, KvDMR in 8% and SNRPN/SNURF ICR
      in 4%. Variation in methylation was significantly greater in breast tissue from
      cancer patients compared with that in healthy individuals and benign breast
      disease. Aberrant methylation of three or more sites was significantly associated
      with negative estrogen-alpha (Fisher's exact test, p = 0.02) and progesterone-A
      (p = 0.02) receptor status. Aberrant events and increased variation in imprinted
      gene DNA methylation, therefore, seem to be frequent in invasive breast cancer
      and are associated with negative estrogen and progesterone receptor status,
      without loss of monoallelic expression.

PMID- 25560177
TI  - Age-related increase in IL-17 activates pro-inflammatory signaling in prostate
      cells.
AB  - BACKGROUND: A close relationship between aging, inflammation, and prostate cancer
      is widely accepted. Aging is accompanied by a progressive increase in pro
      inflammatory cytokines, including interleukin 17 (IL-17), a key pro-inflammatory
      cytokine that becomes dysregulated with age. However, the contribution of IL-17
      to age-related prostate tumorigenesis remains unclear. The aim of this study was
      to investigate the role of age-related IL-17 dysregulation in prostate
      tumorigenesis. METHODS: Serum and splenic T-lymphocytes from young GPAT-1 knock
      out aging-mimic T cell mice as well as young and aged wild-type mice were
      collected. shRNA was used to knock down the IL-17 receptor in LNCaP prostate
      cancer cells and RWPE-1 non-transformed prostate epithelial cells, which were
      then exposed to the mouse sera or conditioned media from stimulated T
      lymphocytes. NF-kappaB activation, NF-kappaB target gene expression, and cell
      proliferation were all measured in these cells by luciferase assay, qPCR, Western
      blot analysis, and MTT assay, respectively. RESULTS: T-lymphocyte-secreted IL-17
      from aging-mimic mice induced NF-kappaB activity and target gene expression in
      LNCaP and RWPE-1 cells. It also promoted proliferation of these cells.
      CONCLUSION: Aging-mimic T cell mice produce increased levels of IL-17, which
      stimulates the pro-inflammatory NF-kappaB pathway in prostate epithelial cells.
      NF-kappaB increases inflammation, carcinogenesis and metastatic potential in the
      prostate. These findings provide evidence that the dysregulation of cytokine
      production seen in aged T cells may directly contribute to the increased risk for
      prostate cancer in the elderly.

PMID- 25560178
TI  - The contribution of NADPH thioredoxin reductase C (NTRC) and sulfiredoxin to 2
      Cys peroxiredoxin overoxidation in Arabidopsis thaliana chloroplasts.
AB  - Hydrogen peroxide is a harmful by-product of photosynthesis, which also has
      important signalling activity. Therefore, the level of hydrogen peroxide needs to
      be tightly controlled. Chloroplasts harbour different antioxidant systems
      including enzymes such as the 2-Cys peroxiredoxins (2-Cys Prxs). Under oxidizing
      conditions, 2-Cys Prxs are susceptible to inactivation by overoxidation of their
      peroxidatic cysteine, which is enzymatically reverted by sulfiredoxin (Srx). In
      chloroplasts, the redox status of 2-Cys Prxs is highly dependent on NADPH
      thioredoxin reductase C (NTRC) and Srx; however, the relationship of these
      activities in determining the level of 2-Cys Prx overoxidation is unknown. Here
      we have addressed this question by a combination of genetic and biochemical
      approaches. An Arabidopsis thaliana double knockout mutant lacking NTRC and Srx
      shows a phenotype similar to the ntrc mutant, while the srx mutant resembles wild
      type plants. The deficiency of NTRC causes reduced overoxidation of 2-Cys Prxs,
      whereas the deficiency of Srx has the opposite effect. Moreover, in vitro
      analyses show that the disulfide bond linking the resolving and peroxidatic
      cysteines protects the latter from overoxidation, thus explaining the dominant
      role of NTRC on the level of 2-Cys Prx overoxidation in vivo. The overoxidation
      of chloroplast 2-Cys Prxs shows no circadian oscillation, in agreement with the
      fact that neither the NTRC nor the SRX genes show circadian regulation of
      expression. Additionally, the low level of 2-Cys Prx overoxidation in the ntrc
      mutant is light dependent, suggesting that the redox status of 2-Cys Prxs in
      chloroplasts depends on light rather than the circadian clock.

PMID- 25560179
TI  - Abscisic acid (ABA) regulates grape bud dormancy, and dormancy release stimuli
      may act through modification of ABA metabolism.
AB  - In warm-winter regions, induction of dormancy release by hydrogen cyanamide (HC)
      is mandatory for commercial table grape production. Induction of respiratory
      stress by HC leads to dormancy release via an uncharacterized biochemical cascade
      that could reveal the mechanism underlying this phenomenon. Previous studies
      proposed a central role for abscisic acid (ABA) in the repression of bud meristem
      activity, and suggested its removal as a critical step in the HC-induced cascade.
      In the current study, support for these assumptions was sought. The data show
      that ABA indeed inhibits dormancy release in grape (Vitis vinifera) buds and
      attenuates the advancing effect of HC. However, HC-dependent recovery was
      detected, and was affected by dormancy status. HC reduced VvXERICO and VvNCED
      transcript levels and induced levels of VvABA8'OH homologues. Regulation of these
      central players in ABA metabolism correlated with decreased ABA and increased ABA
      catabolite levels in HC-treated buds. Interestingly, an inhibitor of ethylene
      signalling attenuated these effects of HC on ABA metabolism. HC also modulated
      the expression of ABA signalling regulators, in a manner that supports a
      decreased ABA level and response. Taken together, the data support HC-induced
      removal of ABA-mediated repression via regulation of ABA metabolism and
      signalling. Expression profiling during the natural dormancy cycle revealed that
      at maximal dormancy, the HC-regulated VvNCED1 transcript level starts to drop. In
      parallel, levels of VvA8H-CYP707A4 transcript and ABA catabolites increase
      sharply. This may provide initial support for the involvement of ABA metabolism
      also in the execution of natural dormancy. 

PMID- 25560180
TI  - Laparoscopic versus open distal pancreatectomy for ductal adenocarcinoma: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Laparoscopic distal pancreatectomy was proposed as an oncologically
      safe approach for pancreatic ductal adenocarcinoma. METHODS: A systematic review
      of the studies comparing laparoscopic and open distal pancreatectomy was
      conducted. The primary endpoint was an R0 resection rate. The secondary endpoints
      were intra- and postoperative results, tumour size, mean harvested lymph node,
      number of patients eligible for adjuvant therapy and overall survival. RESULTS:
      Five comparative case control studies involving 261 patients (30.7% laparoscopic
      and 69.3% open) who underwent a distal pancreatectomy were included. The R0
      resection rate was similar between the two groups (P = 0.53). The laparoscopic
      group had longer operative times (P = 0.04), lesser blood loss (P = 0.01), a
      shorter hospital stay (P < 0.001) and smaller tumour size (P = 0.04) as compared
      with the laparotomic group. Overall morbidity, postoperative pancreatic fistula,
      reoperation, mortality and number of patients eligible for adjuvant therapy were
      similar. The mean harvested lymph nodes were comparable in the two groups (P =
      0.33). The laparoscopic approach did not affect the overall survival rate (P =
      0.32). CONCLUSION: Even if the number of patients compared is underpowered, the
      laparoscopic approach in the treatment of PDAC seems to be safe and efficacious.
      However, additional prospective, randomised, multicentric trials are needed to
      correctly evaluate the laparoscopic approach in PDAC.

PMID- 25560181
TI  - Benign solid tumors of the liver: management in the modern era.
AB  - BACKGROUND: Recently, there has been a growing interest in solid benign liver
      tumors as the understanding of the pathogenesis and molecular underpinning of
      these lesions continues to evolve. We herein provide an evidence-based review of
      benign solid liver tumors with particular emphasis on the diagnosis and
      management of such tumors. METHODS: A search of all available literature on
      benign hepatic tumors through a search of the MEDLINE/PubMed electronic database
      was conducted. RESULTS: New diagnostic and management protocols for benign liver
      tumors have emerged, as well as new insights into the molecular pathogenesis. In
      turn, these data have spawned a number of new studies seeking to correlate
      molecular, clinicopathological, and clinical outcomes for benign liver tumors. In
      addition, significant advances in surgical techniques and perioperative care have
      reduced the morbidity and mortality of liver surgery. Despite current data that
      supports conservative management for many patients with benign liver tumors,
      patients with severe preoperative symptomatic disease seem to benefit
      substantially from surgical treatment based on quality of life data. CONCLUSION:
      Future studies should seek to further advance our understanding of the underlying
      pathogenesis and natural history of benign liver tumors in order to provide
      clinicians with evidence-based guidelines to optimize treatment of patients with
      these lesions.

PMID- 25560182
TI  - The rise in appendiceal cancer incidence: 2000-2009.
AB  - PURPOSE: Appendiceal cancer is a rare and potentially aggressive malignancy. The
      objectives of this study were to characterize secular demographic patterns of
      disease and to determine survival by using a population-based data source.
      METHODS: Using the Surveillance, Epidemiology, and End Results database, we
      conducted a retrospective cohort analysis of patients treated from 2000-2009.
      RESULTS: We identified 4765 patients with appendiceal cancer. The incidence of
      appendiceal cancer increased by 54% from 2000 (0.63 per 100,000) to 2009 (0.97
      per 100,000 population). Incidence rates increased across all tumor types,
      stages, age groups, and gender. The most common malignancies were mucinous
      adenocarcinoma (38%), followed by carcinoids (28%), adenocarcinoma-not otherwise
      specified (NOS) (27%), and signet ring cell adenocarcinoma (7%). Larger tumor
      size and older patient age were significantly associated with higher relative
      odds of distant disease at diagnosis (P < 0.0001). Patient and demographic
      characteristics were significantly associated with higher relative hazard of
      death (P < 0.0001). CONCLUSIONS: Although appendiceal cancer is rare, the
      incidence increased significantly in the USA from 2000 to 2009. The cause of this
      trend is not obvious. We did not observe increases differentially associated with
      stage, histology, or demographic characteristics. Further investigation is needed
      to examine factors underlying this increase.

PMID- 25560183
TI  - Usefulness of the log odds of positive lymph nodes to predict and discriminate
      prognosis in gastric carcinomas.
AB  - BACKGROUND: The lymph node ratio (LNR) and log odds of positive lymph nodes
      (LODDS) have been proposed to minimize the stage migration phenomenon. The value
      of the LODDS and LNR staging systems to predict and discriminate prognosis was
      assessed and compared to the International Union Against Cancer (UICC) TNM
      classification (pN). METHODS: Three hundred and twenty-six patients with gastric
      carcinoma were retrospectively studied. Disease-specific survival rates were
      calculated for every pN, LNR, and LODDS category. RESULTS: Four LNR categories
      (0, 1-25, 26-75, and >76 %) and four LODDS categories (-5 to -3, > -3 to -1, > -1
      to 3, and >3 to 5) were established. In the multivariate analysis, only the stage
      pT3-4 versus pT1-2 (HR 1.88, 95 % CI 1.11-3.20, p=0.02) and LODDS as continuous
      variable (HR 1.40, 95 % CI 1.21-1.61, p<0.001) remained as independent prognostic
      factors. In patients with <16 lymph nodes retrieved, only the LODDS system could
      discriminate different disease-specific survival curves for every category. LODDS
      categories were able to discriminate subgroups with different prognoses in pN
      stages and LNR categories. CONCLUSIONS: The LODDS staging system was superior to
      the pN classification and LNR system to discriminate risk prognosis especially in
      patients with an insufficient number of retrieved lymph nodes.

PMID- 25560184
TI  - En bloc resection of the hepatoduodenal ligament for advanced biliary malignancy.
AB  - BACKGROUND: En bloc resection of the hepatoduodenal ligament (HDL) for advanced
      biliary malignancy by hepato-ligamento-pancreatoduodenectomy (HLPD) or
      hepatoligamentectomy (HL) remains challenging, and only short-term outcomes have
      been reported. We showed our surgical technique of HLPD and HL, and
      retrospectively investigated surgical outcomes of the patients. METHODS: Between
      2003 and 2014, we performed four HLPD and three HL including major hepatectomy
      with concomitant caudate lobectomy. Portal vein reconstruction (PVR) was
      performed with a right external iliac vein graft, and hepatic artery
      reconstruction (HAR) was accomplished with the heterogeneous artery using the
      continuous suturing method. RESULTS: Mean operation time and blood loss were 575
      +/- 111 min and 1539 +/- 950 mL, respectively, and patency of the reconstructed
      vessels was confirmed postoperatively in all cases. Histologically, negative
      surgical margins (R0) were achieved in 57% of patients, while the resected
      vascular invasion was confirmed in all patients. Overall morbidity was high at
      57%, but we have achieved no postoperative mortality. Overall median survival
      time of the patients was 36 months, and a patient of HL survived over 5 years.
      CONCLUSIONS: En bloc resection of the HDL based on steady vascular reconstruction
      can improve the surgical outcome of biliary cancer in selected patients.

PMID- 25560185
TI  - Characterizing readmission in ulcerative colitis patients undergoing restorative
      proctocolectomy.
AB  - BACKGROUND: Postoperative readmissions increase costs and affect patient quality
      of life. Ulcerative colitis (UC) patients are at a high risk for hospital
      readmission following restorative proctocolectomy (RP). OBJECTIVE: The objective
      of this study is to characterize UC patients undergoing RP and identify causes
      and risk factors for readmission. DESIGN: A retrospective review of a
      prospectively maintained institutional database was performed. Postoperative
      readmission rates and reasons for readmission were examined following RP.
      Univariate and multivariate analyses were performed to evaluate for risk factors
      associated with readmission. RESULTS: Of 533 patients who met our inclusion
      criteria, 18.2 % (n = 97) were readmitted within 30 days while 22.7 % (n = 121)
      were readmitted within 90 days of stage I of RP. Younger patient age (OR 1.825,
      95 % CI 1.139-2.957), laparoscopic approach (OR 1.943, 95 % CI 1.217-3.104), and
      increased length of initial stay (OR 1.155, 95 % CI 1.090-1.225) were all
      associated with 30-day readmission. The most common reason for readmission was
      dehydration/ileus/partial bowel obstruction, with 10 % of patients readmitted for
      this reason within 30 days. CONCLUSIONS: Patients undergoing restorative
      proctocolectomy are at high risk for readmission, particularly following the
      first stage of the operation. Novel treatment pathways to prevent ileus and
      dehydration as an outpatient may decrease the rates of readmission following RP.

PMID- 25560186
TI  - Laparoscopic conversion of failed silastic ring vertical gastroplasty (SRVG) and
      vertical banded gastroplasty (VBG) into biliopancreatic diversion (BPD).
AB  - BACKGROUND: The Silastic ring vertical gastroplasty (SRVG), a newer modification
      of Mason's vertical banded gastroplasty (VBG), was the restrictive procedure of
      choice for many bariatric surgeons before the advent of the laparoscopic
      adjustable gastric banding. However, a high rate of reoperations for failure and
      severe complications was reported in long-term studies. Around 50% of the
      patients underwent conversion to other bariatric procedures. OBJECTIVES: The aim
      of this study is to report our experience in laparoscopic conversion of failed
      VBG and SRVG to biliopancreatic diversion (BPD). SETTINGS: The setting of the
      study was at the University hospital. METHODS: Between March 2010 and July 2013,
      12 patients underwent laparoscopic conversion of VBG and SRVG to BPD. Using a
      prospectively collected database, we analyzed their data and outcomes. RESULTS:
      Eighty-six percent of the conversions were successfully completed
      laparoscopically. The mean operative time was 220 min. There was no mortality.
      Perioperative complications occurred in four patients (33%). One (9%) late
      complication, an adhesional small bowel obstruction, was encountered later than
      30 days postoperatively. The follow-up rate was 100%, but only three patients
      reached 3 years at the time of this writing. At a mean follow-up of 19 (3-40)
      months, the mean body mass index (BMI) decreased from 45.3 to 27.8 kg/m2. Percent
      excess weight loss (EWL) was 65.7, and 86.3% at 1 and 3 years, respectively.
      CONCLUSION: Laparoscopic conversion of failed VBG to BPD is feasible and
      effective in further reducing weight in morbidly obese patients. Weight loss
      continues beyond the first postoperative year. However, the complication rate is
      much higher than in the primary procedure.

PMID- 25560187
TI  - Vitamin D receptor gene polymorphisms and steroid receptor status among Saudi
      women with breast cancer.
AB  - The vitamin D receptor (VDR) is a mediator for the cellular effects of vitamin D
      and interacts with other cell signaling pathways that influence cancer
      development. We evaluated the associations of the FOK1 and Taq1 VDR polymorphisms
      and breast cancer risk and possible effect modification by steroid receptor
      status of the tumor. This case-control study includes 95 breast cancer patients
      and 100 age-matched controls. Genotyping for VDR FOK1 and Taq1 polymorphisms was
      performed using polymerase chain reaction-based restriction fragment length
      polymorphism. Level of 25(OH)D in serum was determined using ELISA.
      Immunohistochemical studies were performed for estrogen receptors (ER) and
      progesterone receptors (PR). The frequencies of ff genotype were significantly
      increased in the breast cancer group compared to the control group. Carriers of
      the f allele were significantly more likely to develop BC. We observed a
      statistically significant interaction for the Fok1 polymorphism and ER status.
      Our results demonstrated that FOK1 f. genotype and f allele have an important
      role in breast cancer risk in Saudi patients.

PMID- 25560188
TI  - Pleiotropic effects of TaMYB3R1 on plant development and response to osmotic
      stress in transgenic Arabidopsis.
AB  - In a previous study, we isolated and characterized TaMYB3R1, a MYB3R gene, from
      wheat (Triticum aestivum L.). In vitro assays showed that the TaMYB3R1 protein is
      localized to the nucleus, and functions as an MSA-binding transcriptional
      activator. Expression of TaMYB3R1 is induced by exogenous abscisic acid (ABA) and
      abiotic stress, which encouraged us to further investigate its function in
      planta. In the present study, we generated transgenic Arabidopsis plants
      overexpressing TaMYB3R1. Compared with wild-type plants, the transgenic lines
      produced more rosette leaves, and thus more inflorescences, but the plants showed
      delayed development at the reproductive stage. The TaMYB3R1 protein also
      functions in the osmotic stress response. Transgenic Arabidopsis plants showed
      enhanced tolerance to drought and salt stresses, and the tolerance phenotype was
      conveyed by limiting transpiration through increasing stomatal closure as well as
      reducing water loss. In addition, TaMYB3R1 influenced the expression of both ABA
      dependent and ABA-independent responsive genes, implicating TaMYB3R1 in diverse
      osmotic stress-response mechanisms in Arabidopsis. Our study sheds light on novel
      functions of a plant MYB3R protein.

PMID- 25560189
TI  - Genotype frequencies of VKORC1 and CYP2C9 in native and Mestizo populations from
      Mexico, potential impact for coumarin dosing.
AB  - The collection of pharmacogenetic variants in Mexican populations remains
      incomplete, thus, we aimed to characterize the genotype frequency of 11 SNP on
      CYP2C9 and VKORC1 in more than one-thousand individuals, and to explore their
      potential impact on coumarin dosing. In natives, genotype frequencies indicate
      that over 92% would reflect an extensive metabolism. For Mestizo populations, the
      proportion of CYP2C9 extensive (79%), intermediate (20.0%) and poor metabolizers
      (1.0%) was significantly different from that of natives, and varied among the
      different states of Mexico. Genotype frequencies of 7 SNP on VKORC1, were more
      homogenously distributed among natives and Mestizos. VKORC1 haplotype analysis
      revealed that most natives can be grouped into haplotypes H1 or H7-H8, while
      Mestizos showed a wider frequency distribution for other haplotypes. Our
      observations confirm previous reports on the genotype distribution of major
      CYP2C9 alleles, and contribute to the collection of genotype frequencies on
      relevant VKORC1 variants. 

PMID- 25560190
TI  - Managing posttraumatic stress disorder and major depression in women veterans
      during the perinatal period.
AB  - The recent surge in Operation Enduring Freedom/Operation Iraqi Freedom/Operation
      New Dawn (OEF/OIF/OND) era women Veterans, most of whom are younger compared to
      other women Veterans, presenting with mental health issues is expected to pose
      new clinical challenges. Treatment of mental health conditions in women Veterans
      is not considered comprehensive without adequate examination of the impact of
      reproductive events across the life span, such as their menstrual cycle,
      pregnancy and postpartum period, and menopausal transition. The overarching aim
      of this article is to discuss emerging clinical issues in managing common
      psychiatric conditions such as posttraumatic stress disorder and major depression
      during pregnancy and postpartum period in the VA healthcare system and secondly,
      to identify steps to advance the knowledge and understanding of these complex
      issues. Information to be gained in this area has immediate clinical application
      in the overall management of major psychiatric conditions in women Veterans
      during pregnancy and postpartum, and implications for policy-making decisions. 

PMID- 25560191
TI  - Well-differentiated neuroendocrine tumor of the breast with recurrence due to
      needle tract seeding.

PMID- 25560193
TI  - Phenomenological subtypes of mania and their relationships with substance use
      disorders.
AB  - OBJECTIVE: The aim of the present study was to determine the distinct clusters of
      subtypes among patients with bipolar disorder (BD) and the relationship between
      the clinical features of BD patients, particularly substance use disorders (SUDs)
      and the clusters. METHOD: The present study initially assessed 96 inpatients who
      were hospitalized in the psychiatric clinic of Bakirkoy Prof. Mazhar Osman
      Training and Research Hospital for Psychiatry and Neurology, for a BD manic
      episode. All patients were evaluated during the initial 3 days of their admission
      using the Young Mania Rating Scale (YMRS), the Montgomery-Asberg Depression
      Rating Scale (MADRS),the Scale for the Assessment of Positive Symptoms (SAPS),
      the Michigan Alcoholism Screening Test (MAST) and a sociodemographic
      questionnaire. The factor structures of the psychopathological scale items were
      determined with factor analyses and based on the factor loadings, cluster
      analyses were performed. The relationships among the clusters and the clinical
      variables were then evaluated. RESULTS: The factor analyses generated three
      factors: increased psychomotor activity, dysphoria, and psychosis. A hierarchical
      cluster analysis was applied to the three factor loadings, and revealed that
      factor 1 (increased psychomotor activity) was high in cluster 1 and that the
      effects of factors 2 (dysphoria) and 3 (psychosis) were high in cluster 2. Within
      cluster 1 (Psychomotor elevation), 39% of patients were diagnosed with an alcohol
      use disorder while 31.6% of patients in the cluster 2 (dysphoric-psychotic) were
      diagnosed with both alcohol and cannabis use disorders. Within cluster 2
      (dysphoric-psychotic), 47.4% of patients had one suicide attempt and 21.1% of
      patients had two or more attempts during their lifetime. CONCLUSION: There was a
      significant difference in the presence of SUDs between patients with psychomotor
      elevation and patients in dysphoric-psychotic cluster. This may be point out that
      pure manic patients with BD self-medicate using the sedative effects of alcohol
      and the causal relationship between cannabis and psychosis. Using a dimensional
      approach to study BD may enhance detection of the biological correlates of BD and
      improve the treatment and outcomes of the disorder.

PMID- 25560192
TI  - The roles of resilience and childhood trauma history: main and moderating effects
      on postpartum maternal mental health and functioning.
AB  - OBJECTIVE: Recently postpartum women participated to investigate main and
      moderating influences of resilience and childhood history of maltreatment on
      posttraumatic stress disorder (PTSD), major depressive disorder (MDD), parental
      sense of mastery, and family functioning. METHOD: At 4-months postpartum, 214
      mothers (145 with a history of childhood abuse or neglect) completed interviews
      assessing mental health symptoms, positive functioning, resilience and trauma
      history. Multiple and moderated linear regression with the Connor-Davidson
      Resilience Scale (CD-RISC) and Childhood Trauma Questionnaires (CTQ) were
      conducted to assess for main and moderating effects. RESULTS: Resilience,
      childhood trauma severity, and their interaction predicted postpartum PTSD and
      MDD. In mothers without childhood maltreatment, PTSD was absent irrespective of
      CD-RISC scores. However, for those with the highest quartile of CTQ severity, 8%
      of those with highest resilience in contrast with 58% of those with lowest CD
      RISC scores met PTSD diagnostic criteria. Similar, in those with highest
      resilience, no mothers met criteria for postpartum MDD, irrespective of childhood
      trauma, while for those with lowest quartile of resilience, 25% with lowest CTQ
      severity and 68% of those with highest CTQ severity were depressed. The CD-RISC,
      but not the CTQ, was predictive of postpartum sense of competence. The CD-RISC
      and the CTQ were predictive of postpartum family functioning, though no
      moderating influence of resilience on childhood trauma was found. CONCLUSIONS:
      Resilience is associated with reduced psychopathology and improved wellbeing in
      all mothers. It further serves as a buffer against psychiatric symptoms following
      childhood trauma. Such findings may assist in identification of those at greatest
      risk of adverse functioning postpartum, utilization of resilience-enhancing
      intervention may benefit perinatal wellness, and reduce intergenerational
      transmission of risk.

PMID- 25560194
TI  - Cognitive markers of psychotic unipolar depression: a meta-analytic study.
AB  - BACKGROUND: The goal of the current meta-analysis was to review and examine in
      detail the features of cognitive performance in psychotic (MDDP) versus non
      psychotic (MDD) major depressive disorder. METHODS: An electronic literature
      search was performed to find studies comparing cognitive performance in MDDP
      versus MDD. A meta-analysis of broad cognitive domains (processing speed,
      reasoning/problem solving, verbal learning, visual learning, attention/working
      memory) and individual cognitive tasks was conducted on all included studies
      (n=12). Demographic and clinical features were investigated via meta-regression
      analysis as moderators of cognitive performance. RESULTS: No difference in socio
      demographic and clinical variables was detected between groups. In general, a
      poorer cognitive performance was detected in MDDP versus MDD subjects (ES=0.38),
      with a greater effect size in drug-free patients (ES=0.69). MDDP patients were
      more impaired in verbal learning (ES=0.67), visual learning (ES=0.62) and
      processing speed (ES=0.71) tasks. A significantly poorer performance was also
      detected in MDDP patients for individual tasks as Trail Making Test A, WAIS-R
      digit span backward and WAIS-R digit symbol. Age resulted to have a negative
      effect on tasks involved in working memory performance. CONCLUSION: In line with
      previous meta-analyses, our findings seem to support an association between
      psychosis and cognitive deficits in the context of affective disorders. Psychosis
      during the course of MDD is associated with poorer cognitive performance in some
      specific cognitive domains, such as visual and verbal learning and executive
      functions.

PMID- 25560195
TI  - An Articular Cartilage Repair Model in Common C57Bl/6 Mice.
AB  - To analyze the genetic and biomolecular mechanisms underlying cartilage repair,
      an optimized mouse model of osteochondral repair is required. Although several
      models of articular cartilage injury in mice have recently been established, the
      articular surface in adult C57Bl/6 mice heals poorly. Since C57Bl/6 mice are the
      most popular strain of genetically manipulated mice, an articular cartilage
      repair model using C57Bl/6 mice would be helpful for analysis of the mechanisms
      of cartilage repair. The purpose of this study was to establish a cartilage
      repair model in C57Bl/6 mice using immature animals. To achieve this goal, full
      thickness injuries were generated in 3-week-old (young), 4-week-old (juvenile),
      and 8-week-old (adult) C57Bl/6 mice. To investigate the reproducibility and
      consistency of full-thickness injuries, mice were sacrificed immediately after
      operation, and cartilage thickness at the patellar groove, depth of the cartilage
      injury, cross-sectional width, and cross-sectional area were compared among the
      three age groups. The depth of cartilage injury/cartilage thickness ratio
      (%depth) and the coefficient of variation (CV) for each parameter were also
      calculated. At 8 weeks postoperatively, articular cartilage repair was assessed
      using a histological scoring system. With respect to the reproducibility and
      consistency of full-thickness injuries, cartilage thickness, depth of cartilage
      injury, and cross-sectional area were significantly larger in young and juvenile
      mice than in adult mice, whereas cross-sectional width and %depth were almost
      equal among the three age groups. CVs of %depths were less than 10% in all
      groups. With respect to articular cartilage repair, young and juvenile mice
      showed superior results. In conclusion, we established a novel cartilage repair
      model in C57Bl/6 mice. This model will be valuable in achieving mechanistic
      insights into the healing process of the joint surface, as it will facilitate the
      use of genetically modified mice, which are most commonly developed on a C57Bl/6
      background. 

PMID- 25560196
TI  - A regulatory similarity measure using the location information of transcription
      factor binding sites in Saccharomyces cerevisiae.
AB  - BACKGROUND: Defining a measure for regulatory similarity (RS) of two genes is an
      important step toward identifying co-regulated genes. To date, transcription
      factor binding sites (TFBSs) have been widely used to measure the RS of two genes
      because transcription factors (TFs) binding to TFBSs in promoters is the most
      crucial and well understood step in gene regulation. However, existing TFBS-based
      RS measures consider the relation of a TFBS to a gene as a Boolean (either
      'presence' or 'absence') without utilizing the information of TFBS locations in
      promoters. RESULTS: Functional TFBSs of many TFs in yeast are known to have a
      strong positional preference to occur in a small region in the promoters. This
      biological knowledge prompts us to develop a novel RS measure that exploits the
      TFBS location information. The performances of different RS measures are
      evaluated by the fraction of gene pairs that are co-regulated (validated by
      literature evidence) by at least one common TF under different RS scores. The
      experimental results show that the proposed RS measure is the best co-regulation
      indicator among the six compared RS measures. In addition, the co-regulated genes
      identified by the proposed RS measure are also shown to be able to benefit three
      co-regulation-based applications: detecting gene co-function, gene co-expression
      and protein-protein interactions. CONCLUSIONS: The proposed RS measure provides a
      good indicator for gene co-regulation. Besides, its good performance reveals the
      importance of the location information in TFBS-based RS measures.

PMID- 25560197
TI  - Innovative approach for urease inhibition by Ficus carica extract-fabricated
      silver nanoparticles: An in vitro study.
AB  - In the present study, a rapid, low-cost, and ecofriendly method of stable silver
      nanoparticles (AgNPs) synthesis using leaves extract of Ficus carica (F. carica),
      a plant with diverse metabolic consortium, is reported for the first time. An
      absorption peak at 422 nm in UV-Vis spectroscopy, a spherical shape with an
      average size of 21 nm in transmission electron microscopy, and crystalline nature
      in X-ray powder diffraction studies were observed for the synthesized AgNPs.
      Fourier transform infrared analysis indicated that proteins of F. carica might
      have a vital role in AgNP synthesis and stabilization. AgNPs were found to
      inhibit urease, a key enzyme responsible for the survival and pathogenesis of the
      bacterium, Helicobacter pylori. Inhibition of urease by AgNPs was monitored
      spectrophotometrically by the evaluation of ammonia release. The urease
      inhibition potential of AgNPs can be explored in the treatment of H. pylori by
      preparing novel combinations of standard drugs with AgNPs- or AgNPs-encapsulated
      drug molecules.

PMID- 25560198
TI  - The synthetic curcuminoid BHMC restores endotoxin-stimulated HUVEC
      dysfunction:Specific disruption on enzymatic activity of p38 MAPK.
AB  - 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC) has been proven to
      selectively inhibit the synthesis of proinflammatory mediators in
      lipopolysaccharide-induced U937 monocytes through specific interruption of p38
      Mitogen-Activated Protein Kinase enzymatic activity and improves the survival
      rate in a murine lethal sepsis model. The present study addressed the effects of
      BHMC upon lipopolysaccharide-induced endothelial dysfunction in human umbilical
      vein endothelial cells to determine the underlying mechanisms. The cytotoxicity
      effect of BHMC on HUVEC were determined by MTT assay. The effects of BHMC on
      endothelial dysfunction induced by lipopolysaccharide such as endothelial
      hyperpermeability, monocyte-endothelial adhesion, transendothelial migration, up
      regulation of adhesion molecules and chemokines were evaluated. The effects of
      BHMC at transcriptional and post-translational levels were determined by Reverse
      Transcriptase-Polymerase Chain Reaction and Western Blots. The mode of action of
      BHMC was dissected by looking into the activation of Nuclear Factor-kappa B and
      Mitogen-Activated Protein Kinases. BHMC concentration-dependently reduced
      endothelial hyperpermeability, leukocyte-endothelial cell adhesion and monocyte
      transendothelial migration through inhibition of the protein expression of
      adhesion molecules (Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion
      Molecule-1) and secretion of chemokines (Monocyte Chemotactic Protein-1) at the
      transcriptional level. BHMC restored endothelial dysfunction via selective
      inhibition of p38 Mitogen-Activated Protein Kinase enzymatic activity which
      indirectly prevents the activation of Nuclear Factor-kappaB and Activator Protein
      1 transcription factors. These findings further support earlier observations on
      the inhibition of BHMC on inflammatory events through specific disruption of p38
      Mitogen-Activated Protein Kinase enzymatic activity and provide new insights into
      the inhibitory effects of BHMC on lipopolysaccharide-induced endothelial
      dysfunction. 

PMID- 25560199
TI  - The influence of prior training on GPs' attitudes to sickness absence
      certification post-fit note.
AB  - Aim To investigate the attitudes to health and work of general practitioners
      (GPs) with training in occupational medicine (OM) compared with non-OM trained
      GPs, since the introduction of the fit note. BACKGROUND: Changes to the UK
      sickness certification system since 2010 and the introduction of the fit note
      required GPs to change their focus to what patients can do, rather than what they
      cannot do in relation to work. In an effort to reduce the UK sickness absence
      burden, GPs completion of the fit note should help to keep people in work, or
      assist patients to return to work as quickly as possible after a period of
      absence. METHODS: Questionnaire data were collected via the 7th National General
      Practitioner Worklife Survey. Findings Results indicate that responses from GPs
      who had undertaken training in OM, and GPs having received some form of work and
      health training in the 12-month period before the study were associated with
      significantly more positive attitudes to patients' returning to work and to the
      fit note. This study reveals evidence of a difference between trained and non
      trained GPs in their attitude to the fit note, and to work and health generally.
      Further work investigating the effect of specific training in OM on the
      management and recognition of ill-health by GPs is recommended.

PMID- 25560200
TI  - [Dorsal nasal rotation flap (Rieger flap) for the repair of nasal-tip defect
      secondary to refractory nodular amyloidosis].

PMID- 25560202
TI  - Internal dynamics and activated processes in soft-glassy materials.
AB  - Plastic rearrangements play a crucial role in the characterization of soft-glassy
      materials, such as emulsions and foams. Based on numerical simulations of soft
      glassy systems, we study the dynamics of plastic rearrangements at the
      hydrodynamic scales where thermal fluctuations can be neglected. Plastic
      rearrangements require an energy input, which can be either provided by external
      sources, or made available through time evolution in the coarsening dynamics, in
      which the total interfacial area decreases as a consequence of the slow evolution
      of the dispersed phase from smaller to large droplets/bubbles. We first
      demonstrate that our hydrodynamic model can quantitatively reproduce such
      coarsening dynamics. Then, considering periodically oscillating strains, we
      characterize the number of plastic rearrangements as a function of the external
      energy-supply, and show that they can be regarded as activated processes induced
      by a suitable "noise" effect. Here we use the word noise in a broad sense,
      referring to the internal non-equilibrium dynamics triggered by spatial random
      heterogeneities and coarsening. Finally, by exploring the interplay between the
      internal characteristic time-scale of the coarsening dynamics and the external
      time-scale associated with the imposed oscillating strain, we show that the
      system exhibits the phenomenon of stochastic resonance, thereby providing further
      credit to the mechanical activation scenario. 

PMID- 25560201
TI  - Fluctuations in [11C]SB207145 PET binding associated with change in threat
      related amygdala reactivity in humans.
AB  - Serotonin critically affects the neural processing of emotionally salient
      stimuli, including indices of threat; however, how alterations in serotonin
      signaling contribute to changes in brain function is not well understood.
      Recently, we showed in a placebo-controlled study of 32 healthy males that brain
      serotonin 4 receptor (5-HT4) binding, assessed with [(11)C]SB207145 PET, was
      sensitive to a 3-week intervention with the selective serotonin reuptake
      inhibitor fluoxetine, supporting it as an in vivo model for fluctuations in
      central serotonin levels. Participants also underwent functional magnetic
      resonance imaging while performing a gender discrimination task of fearful,
      angry, and neutral faces. This offered a unique opportunity to evaluate whether
      individual fluctuations in central serotonin levels, indexed by change in
      [(11)C]SB207145 binding, predicted changes in threat-related reactivity (ie, fear
      and angry vs neutral faces) within a corticolimbic circuit including the amygdala
      and medial prefrontal and anterior cingulate cortex. We observed a significant
      association such that decreased brain-wide [(11)C]SB207145 binding (ie, increased
      brain serotonin levels) was associated with lower threat-related amygdala
      reactivity, whereas intervention group status did not predict change in
      corticolimbic reactivity. This suggests that in the healthy brain,
      interindividual responses to pharmacologically induced and spontaneously
      occurring fluctuations in [(11)C]SB207145 binding, a putative marker of brain
      serotonin levels, affect amygdala reactivity to threat. Our finding also supports
      that change in brain [(11)C]SB207145 binding may be a relevant marker for
      evaluating neurobiological mechanisms underlying sensitivity to threat and
      serotonin signaling. 

PMID- 25560203
TI  - Transient Horner's syndrome following thoracic epidural anesthesia for
      mastectomy: a prospective observational study.
AB  - PURPOSE: Transient Horner's syndrome is an uncommon complication of epidural
      anesthesia, though its exact incidence in thoracic epidural anesthesia is not
      clear. Therefore, this study prospectively evaluated the incidence of Horner's
      syndrome after thoracic epidural anesthesia for mastectomy. METHODS: Patients
      scheduled for mastectomy, with or without breast reconstruction, were enrolled in
      this prospective observational study from September 2010 to December 2013.
      Intraoperative thoracic epidural anesthesia was established using 0.375% or 0.5%
      ropivacaine 15 mL with thoracic epidural analgesia continued postoperatively with
      a continuous infusion of 0.15% ropivacaine 2 mL.hr(-1) with fentanyl 8 MUg.hr(
      1). Signs of Horner's syndrome (miosis, ptosis, and hyperemia) were assessed at
      one and two hours as well as one, two, and three days postoperatively. RESULTS:
      Thoracic epidural anesthesia was successful in 439 patients, with six (1.4%) of
      these patients acquiring Horner's syndrome. All signs of Horner's syndrome
      resolved gradually within 180 min of discontinuing the epidural infusion. In one
      patient with Horner's syndrome, a radiographic contrast injection confirmed that
      the drug had spread to the cervical epidural level. CONCLUSION: The incidence of
      Horner's syndrome following thoracic epidural anesthesia and continuous thoracic
      epidural analgesia for mastectomy was 1.4%. The mechanism was consistent with
      cephalic spread of the epidural local anesthetic. This trial was registered at:
      Clinicaltrials.gov, number: NCT02130739.

PMID- 25560204
TI  - Structural instabilities and mechanical properties of U2Mo from first principles
      calculations.
AB  - We perform detailed first principles calculations of the structural parameters at
      zero pressure and high pressure, the elastic properties, phonon dispersion
      relation, and ideal strengths of U2Mo with the C11b structure. In contrast to
      previous theoretical studies, we show that the I4/mmm structure is indeed a
      mechanically and dynamically unstable phase, which is confirmed by the negative
      elastic constant C66 as well as the imaginary phonon modes observed along the
      Sigma1-N-P line. The calculations of ideal strengths for U2Mo are performed along
      the [100], [001], and [110] directions for tension and on (001)[010] and
      (010)[100] slip systems for shear load. The ideal shear strength is about 8.1
      GPa, much smaller than a tension of 18-28 GPa, which indicates that the ductile
      U2Mo alloy will fail by shear rather than by tension. 

PMID- 25560205
TI  - Elevated plasma orexin A levels in a subgroup of patients with schizophrenia
      associated with fewer negative and disorganized symptoms.
AB  - BACKGROUND: Orexin A and B, a pair of hypothalamic neuropeptides also named
      hypocretin 1 and 2, play a role in the regulation of arousal, appetite, reward,
      attention, and cognition. Animal studies showed that antipsychotics can activate
      orexin neurons in a manner correlated with their weight gain liability. However,
      little is known about the role of orexin in patients with schizophrenia. This
      study aimed to investigate the correlation of plasma orexin level with clinical
      symptom profile, neurocognitive functioning and weight gain liability of the
      antipsychotics taken in patients with schizophrenia. METHODS: We measured plasma
      levels of orexin A in 127 patients with schizophrenia and 34 healthy controls by
      radioimmunoassay. In patients, we assessed clinical symptoms on the Positive and
      Negative Syndrome Scale and executive function by the Wisconsin Card Sorting test
      (WCST), and examined their associations with plasma orexin A level. RESULTS:
      Patients with schizophrenia had a significantly higher mean orexin A level than
      healthy controls (60.7+/-37.9 vs. 38.8+/-15.5pg/ml). Patients were divided into
      two subgroups based on their orexin A levels that were distributed in two
      clusters divided by 80pg/ml. Patients in the high-orexin subgroup had
      significantly fewer negative and disorganized symptoms, and tended to have fewer
      perseverative errors, more failure to maintain set yet comparable category
      achieved on the WCST than the normal-orexin subgroup. There was no significant
      difference in orexin A levels among patients taking antipsychotics with different
      weight gain liabilities. CONCLUSION: Higher level of orexin A seems to be related
      to favorable clinical symptom profiles of schizophrenia, but the causal
      relationship needs further clarification.

PMID- 25560206
TI  - Stimulation of glucagon-like peptide-1 secretion by water loading in human.

PMID- 25560207
TI  - Intratesticular, intraperitoneal, and oral administration of thienopyrimidine
      derivatives increases the testosterone level in male rats.

PMID- 25560208
TI  - The effect of dynasore, a blocker of dynamin-dependent endocytosis, on
      spontaneous quantal and non-quantal release of acetylcholine in murine
      neuromuscular junctions.

PMID- 25560209
TI  - The effect of electric stimulation of various frequencies and durations on
      microtubules in frog motor axon terminals.

PMID- 25560210
TI  - The involvement of V1b-subtype vasopressin receptors in regulation of potassium
      ions excretion in the rat kidneys.

PMID- 25560211
TI  - Feeding habits of common eiders Somateria mollissima on the western coast of
      Vaygach Island.

PMID- 25560212
TI  - Downstream migration of early larvae of the European river lamprey Lampetra
      fluviatilis.

PMID- 25560213
TI  - Relationship between root structure of herbaceous dicotyledonous plants and their
      mycorrhizal status.

PMID- 25560214
TI  - Fauna of cottoid fish (Cottoidei) in the area of methane seep in the abyssal of
      Lake Baikal.

PMID- 25560215
TI  - Genetically determined volume of mesophyll cells of birch leaves as an adaptation
      of the photosynthetic apparatus to climate.

PMID- 25560216
TI  - On possibility to identify the saiga antelope (Saiga tatarica) on very-high
      resolution satellite images.

PMID- 25560217
TI  - Higher social distress and lower psycho-social wellbeing: examining the coping
      capacity and health of people with hearing impairment.
AB  - PURPOSE: The objectives of this paper are as follows: (1) propose an explanatory
      model as to how hearing disability may impact on health and (2) examine the
      model's utility. METHODS: Data were collected on the psycho-social wellbeing,
      disability and physical health of farmers (n = 56) participating in an
      intervention to manage the social impacts of hearing disability. Two models were
      proposed and examined using multiple hierarchical linear regression. Model 1 used
      self-rated quality of life and model 2 used capacity to manage hearing and
      listening impairments, as dependent variables. RESULTS: The analyses found that
      physical measures of hearing impairment (audiograms) were not correlated with
      physical or mental health outcomes. However, in model 1, self-confidence and self
      rated ability to manage hearing impairment were most closely associated with
      reduced quality of life (anxiety and diastolic blood pressure were positively
      associated with quality of life). In model 2, higher anxiety and reduced self
      confidence were associated with decreasing ability to successfully manage one's
      hearing impairment. CONCLUSIONS: The findings support the explanatory model that
      stress is higher and wellbeing lower when the fit between the person's coping
      capacity and environmental demands is poor. IMPLICATIONS FOR REHABILITATION: This
      paper demonstrates that anxiety is associated with coping with the psycho-social
      aspects of hearing disability. This finding has important implications for the
      many hearing services, which only provide assessment and devices. To negate
      anxiety and its long-term impacts, rehabilitation providers need to ensure people
      with hearing disability have the capacity to manage the psycho-social aspects of
      communication breakdown.

PMID- 25560222
TI  - Application of BCI systems in neurorehabilitation: a scoping review.
AB  - PURPOSE: To review various types of electroencephalographic activities of the
      brain and present an overview of brain-computer interface (BCI) systems' history
      and their applications in rehabilitation. METHODS: A scoping review of published
      English literature on BCI application in the field of rehabilitation was
      undertaken. IEEE Xplore, ScienceDirect, Google Scholar and Scopus databases were
      searched since inception up to August 2012. All experimental studies published in
      English and discussed complete cycle of the BCI process was included in the
      review. RESULTS AND DISCUSSION: In total, 90 articles met the inclusion criteria
      and were reviewed. Various approaches that improve the accuracy and performance
      of BCI systems were discussed. Based on BCI's clinical application, reviewed
      articles were categorized into three groups: motion rehabilitation, speech
      rehabilitation and virtual reality control (VRC). Almost half of the reviewed
      papers (48%) concentrated on VRC. Speech rehabilitation and motion rehabilitation
      made up 33% and 19% of the reviewed papers, respectively. Among different types
      of electroencephalography signals, P300, steady state visual evoked potentials
      and motor imagery signals were the most common. CONCLUSIONS: This review
      discussed various applications of BCI in rehabilitation and showed how BCI can be
      used to improve the quality of life for people with neurological disabilities. It
      will develop and promote new models of communication and finally, will create an
      accurate, reliable, online communication between human brain and computer and
      reduces the negative effects of external stimuli on BCI performance. Implications
      for Rehabilitation The field of brain-computer interfaces (BCI) is rapidly
      advancing and it is expected to fulfill a critical role in rehabilitation of
      neurological disorders and in movement restoration in the forthcoming years. In
      the near future, BCI has notable potential to become a major tool used by people
      with disabilities to control locomotion and communicate with surrounding
      environment and, consequently, improve the quality of life for many affected
      persons. Electrical field recording at the scalp (i.e. electroencephalography) is
      the most likely method to be of practical value for clinical use as it is simple
      and non-invasive. However, some aspects need future improvements, such as the
      ability to separate close imagery signal (motion of extremities and phalanges
      that are close together).

PMID- 25560224
TI  - On-site quantitative elemental analysis of metal ions in aqueous solutions by
      underwater laser-induced breakdown spectroscopy combined with electrodeposition
      under controlled potential.
AB  - We propose a technique of on-site quantitative analysis of Zn(2+) in aqueous
      solution based on the combination of electrodeposition for preconcentration of Zn
      onto a Cu electrode and successive underwater laser-induced breakdown
      spectroscopy (underwater LIBS) of the electrode surface under electrochemically
      controlled potential. Zinc emission lines are observed with the present technique
      for a Zn(2+) concentration of 5 ppm. It is roughly estimated that the overall
      sensitivity over 10 000 times higher is achieved by the preconcentration.
      Although underwater LIBS suffers from the spectral deformation due to the dense
      plasma confined in water and also from serious shot-to-shot fluctuations, a
      linear calibration curve with a coefficient of determination R(2) of 0.974 is
      obtained in the range of 5-50 ppm. 

PMID- 25560223
TI  - Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic
      resonance imaging as a useful detection method for advanced primary biliary
      cirrhosis.
AB  - AIM: In primary biliary cirrhosis (PBC), damaged hepatocytes resulting from
      chronic cholestasis follow a compensatory mechanism that alters hepatobiliary
      transporter expression to reduce the accumulation of potentially toxic compounds
      such as bile acid. Organic anion transporter peptide 1B3 (OATP1B3), which
      transports agents such as gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic
      acid (Gd-EOB-DTPA), has reduced expression in the late stages of PBC. Therefore,
      we investigated the use of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI)
      as a useful detection method for the advanced staging of PBC. METHODS: Stage I
      III PBC (non-liver cirrhosis [LC]-PBC, n = 12), stage IV (LC-PBC, n = 6), and non
      PBC patients (control group, n = 4) were included in this study. We obtained
      liver tissue samples by percutaneous liver biopsy. Hepatic OATP1B3 expression was
      determined immunohistochemically, and OATP1B3 mRNA levels were assessed using
      real-time reverse transcription polymerase chain reaction. The relative
      enhancement (RE) in the hepatobiliary phase was calculated using the signal
      intensity of Gd-EOB-DTPA-enhanced MRI. RESULTS: Immunohistochemistry revealed
      markedly reduced expression of OATP1B3 in hepatocytes around the central vein in
      LC-PBC patients. Hepatic OATP1B3 mRNA expression in LC-PBC patients was
      significantly lower than that in non-LC-PBC patients (P < 0.05). The RE on MRI
      was significantly decreased in the LC-PBC group (0.33 +/- 0.14) compared with the
      non-LC-PBC (0.91 +/- 0.15, P < 0.01) and control (0.92 +/- 0.20, P < 0.01)
      groups. CONCLUSION: Gd-EOB-DTPA-enhanced MRI may provide a useful detection
      method for liver disease in patients with LC-PBC.

PMID- 25560225
TI  - Identification of conserved and polymorphic STRs for personal genomes.
AB  - BACKGROUND: Short tandem repeats (STRs) are abundant in human genomes. Numerous
      STRs have been shown to be associated with genetic diseases and gene regulatory
      functions, and have been selected as genetic markers for evolutionary and
      forensic analyses. High-throughput next generation sequencers have fostered new
      cutting-edge computing techniques for genome-scale analyses, and cross-genome
      comparisons have facilitated the efficient identification of polymorphic STR
      markers for various applications. RESULTS: An automated and efficient system for
      detecting human polymorphic STRs at the genome scale is proposed in this study.
      Assembled contigs from next generation sequencing data were aligned and
      calibrated according to selected reference sequences. To verify identified
      polymorphic STRs, human genomes from the 1000 Genomes Project were employed for
      comprehensive analyses, and STR markers from the Combined DNA Index System
      (CODIS) and disease-related STR motifs were also applied as cases for evaluation.
      In addition, we analyzed STR variations for highly conserved homologous genes and
      human-unique genes. In total 477 polymorphic STRs were identified from 492 human
      unique genes, among which 26 STRs were retrieved and clustered into three
      different groups for efficient comparison. CONCLUSIONS: We have developed an
      online system that efficiently identifies polymorphic STRs and provides novel
      distinguishable STR biomarkers for different levels of specificity. Candidate
      polymorphic STRs within a personal genome could be easily retrieved and compared
      to the constructed STR profile through query keywords, gene names, or assembled
      contigs.

PMID- 25560226
TI  - Finding the elusive balance between reducing fatigue and enhancing education:
      perspectives from American residents.
AB  - Duty hour restrictions for residency training were implemented in the United
      States to improve residents' educational experience and quality of life, as well
      as to improve patient care and safety; however, these restrictions are by no
      means problem-free. In this paper, we discuss the positive and negative aspects
      of duty hour restrictions, briefly highlighting research on the impact of reduced
      duty hours and the experiences of American residents. We also consider whether
      certain specialties (e.g., Emergency Medicine, Radiology) may be more amenable
      than others (e.g., Surgery) to duty hour restrictions. We conclude that feedback
      from residents is a crucial element that must be considered in any future
      attempts to strike a balance between reducing fatigue and enhancing education. 

PMID- 25560228
TI  - Dear colleague, please, do not ask for ultrasound studies for inguinal hernia
      diagnosis.

PMID- 25560227
TI  - Effects of frequent hemodialysis on blood pressure: Results from the randomized
      frequent hemodialysis network trials.
AB  - Hypertension is a common complication of chronic kidney disease and persists
      among most patients with end-stage renal disease despite the provision of
      conventional thrice weekly hemodialysis (HD). We analyzed the effects of frequent
      HD on blood pressure in the randomized controlled Frequent Hemodialysis Network
      trials. The daily trial randomized 245 patients to 12 months of 6* ("frequent")
      vs. 3* ("conventional") weekly in-center hemodialysis; the nocturnal trial
      randomized 87 patients to 12 months of 6* weekly nocturnal HD vs. 3* weekly
      predominantly home-based hemodialysis. In the daily trial, compared with 3*
      weekly HD, 2 months of frequent HD lowered predialysis systolic blood pressure by
      -7.7 mmHg [95% confidence interval (CI): -11.9 to -3.5] and diastolic blood
      pressure by -3.9 mmHg [95% CI: -6.5 to -1.3]. In the nocturnal trial, compared
      with 3* weekly HD, 2 months of frequent HD lowered systolic blood pressure by 
      7.3 mmHg [95% CI: -14.2 to -0.3] and diastolic blood pressure by -4.2 mmHg [95%
      CI: -8.3 to -0.1]. In both trials, blood pressure treatment effects were
      sustained until month 12. Frequent HD resulted in significantly fewer
      antihypertensive medications (daily: -0.36 medications [95% CI: -0.65 to -0.08];
      nocturnal: -0.44 mediations [95% CI: -0.89 to -0.03]). In the daily trial, the
      relative risk per dialysis session for intradialytic hypotension was lower with
      6*/week HD but given the higher number of sessions per week, there was a higher
      relative risk for intradialytic hypotensive requiring saline administration. In
      summary, frequent HD reduces blood pressure and the number of prescribed
      antihypertensive medications. 

PMID- 25560229
TI  - Formal palladium-catalyzed asymmetric hydrogenolysis of racemic N
      sulfonyloxaziridines.
AB  - Highly enantioselective palladium-catalyzed formal hydrogenolysis of racemic N
      sulfonyloxaziridines has been realized, providing a novel access to sultams with
      up to 99% ee. Preliminary mechanistic insights revealed that the reaction
      proceeded through a N-O bond cleavage, dehydration, and the sequential asymmetric
      hydrogenation. 

PMID- 25560230
TI  - Knowledge, attitudes, and practices of US practitioners who provide pre-travel
      advice.

PMID- 25560231
TI  - Importation index of dengue to determine the most probable origin of importation.

PMID- 25560232
TI  - Effects of miR-9 and tetramethylpyrazine on activation of hepatic stellate cells.
AB  - Micro-RNAs (miRNAs) are involved in regulation of the incidence and development
      of several hepatic diseases. Thus manipulating miRNAs may be a promising
      therapeutic strategy against these entities. In this study hepatic stellate cells
      (HSCs) were transfected with hsa-miR-9 or anti-hsa-miR-9, treated with
      tetramethylpyrazine (TMP), or subjected to treatment with TMP and hsa-miR-9
      transfection (combined treatment group). Then, real-time polymerase chain
      reaction (PCR) was performed to measure mRNA levels of hsa-miR-9. Expression of
      hsa-miR-9 was highest in the combination treatment group compared with other
      groups, and significantly higher than TMP-treated and hsa-miR-9-transfected
      groups (both p<0.05). The anti-hsa-miR-9-transfected group expressed the lowest
      mRNA level of hsa-miR-9 with marked decrease versus control (p<0.05). Downstream
      factors that may be affected by miR-9 such as leptin, alpha-smooth muscle actin
      (SMA), and collagen I, as well as phosphorylation levels of Janus kinase 1
      (JAK1)/signal transducer and activator of transcription 3 (STAT3) were
      investigated at the protein level. All these factors were regulated contrariwise
      to expression trends of hsa-miR-9, showing the lowest level in the combination
      treatment group and highest level in anti-hsa-miR-9-transfected group. These
      results suggest that both transfection of hsa-miR-9 and TMP can lead to
      upregulated endogenous expression of hsa-miR-9, inhibit activation of JAK1/STAT3
      signal pathway induced by leptin, and lead to reduction of alpha-SMA and collagen
      I-thus impeding activation of HSC. 

PMID- 25560233
TI  - Success in incorporating horizontally transferred genes: the H-NS protein.
AB  - The nucleoid-associated protein H-NS silences unwanted expression of acquired
      foreign DNA. Ali and colleagues recently identified which horizontally-acquired
      genes are targeted by H-NS in Salmonella to avoid fitness loss. The reported data
      strengthen our view about the role of H-NS in bacterial evolution driven by
      horizontal gene transfer. 

PMID- 25560235
TI  - Promotion of exocyclic bond cleavages in the decomposition of 1,3
      disilacyclobutane in the presence of a metal filament.
AB  - The primary decomposition of 1,3-disilacyclobutane (DSCB) on a tungsten filament
      and its secondary gas-phase reactions in a hot-wire chemical vapor deposition
      (CVD) reactor have been studied using laser ionization mass spectrometry. Under
      the collision-free conditions, DSCB decomposes on the W filament to produce H2
      molecules with an activation energy of 43.6 +/- 4.1 kJ.mol(-1). With the help of
      the isotope labeling and chemical trapping methods, the mechanistic details in
      the secondary gas-phase reactions important in the hot-wire CVD reactor setup
      have been examined. The dominant pathway has been demonstrated to be the
      insertion of the cyclic 1,3-disilacyclobut-1-ylidene, generated by exocyclic Si-H
      bond rupture, into the Si-H bond in DSCB to form 1,1'-bis(1,3-disilacyclobutane)
      (174 amu). The successful trapping of 1,3-disilacyclobut-1-ylidene by both 1,3
      butadiene and trimethylsilane provides compelling evidence for the existence of
      this cyclic silylene species in the hot-wire CVD reactor with DSCB. Other
      reactions operating in the reactor include the DSCB cycloreversion to form silene
      and the ring opening of DSCB via 1,2-H shift to produce silene/methylsilylene and
      1-methylsilene/silylene. The introduction of an additional Si atom in the four
      membered ring monosilacyclobutane molecule has caused two major changes in the
      reaction chemistry assumed by DSCB: (1) The endocyclic cycloreversion reactions
      that dominate in the decomposition of monosilacyclobutane molecules only play a
      much less important role in the dissociation of DSCB; and (2) the exocyclic bond
      cleavages are promoted in DSCB due to the ring stabilization caused by the
      introduction of one additional Si atom. 

PMID- 25560234
TI  - Detailed investigation of the microbial community in foaming activated sludge
      reveals novel foam formers.
AB  - Foaming of activated sludge (AS) causes adverse impacts on wastewater treatment
      operation and hygiene. In this study, we investigated the microbial communities
      of foam, foaming AS and non-foaming AS in a sewage treatment plant via deep
      sequencing of the taxonomic marker genes 16S rRNA and mycobacterial rpoB and a
      metagenomic approach. In addition to Actinobacteria, many genera (e.g.,
      Clostridium XI, Arcobacter, Flavobacterium) were more abundant in the foam than
      in the AS. On the other hand, deep-sequencing of rpoB did not detect any obligate
      pathogenic mycobacteria in the foam. We found that unknown factors other than the
      abundance of Gordonia sp. could determine the foaming process, because abundance
      of the same species was stable before and after a foaming event over six months.
      More interestingly, although the dominant Gordonia foam former was the closest
      with G. amarae, it was identified as an undescribed Gordonia species by referring
      to the 16S rRNA gene, gyrB and, most convincingly, the reconstructed draft genome
      from metagenomic reads. Our results, based on metagenomics and deep sequencing,
      reveal that foams are derived from diverse taxa, which expands previous
      understanding and provides new insight into the underlying complications of the
      foaming phenomenon in AS. 

PMID- 25560236
TI  - Discovering the brain's cognitive map.

PMID- 25560238
TI  - The paradox of the contrasting roles of chronic magnesium deficiency in metabolic
      disorders and field cancerization.
AB  - Magnesium (Mg(2+)) deficiency is common in metabolic disorders such as obesity,
      type 2 diabetes, and insulin resistance. These disorders are also associated with
      a high incidence of cancer. Mg(2+) is the regulator par excellence of metabolism,
      largely through its role as a cofactor for all phosphoryl transfers in the cell.
      Because Mg(2+) deficiency inhibits energy production it might be expected to
      inhibit tumor production. However, the high incidence of cancer in metabolic
      disorders makes that seem unlikely. In order to understand this seeming paradox,
      it is important to understand the regulatory role of Mg(2+) in normal and
      neoplastic cells. Free Mg(2+) is the primary regulator of glycolysis and the
      Krebs cycle. It also acts as a second messenger for growth factors in regulating
      protein synthesis. Varying Mg(2+) concentrations result in the same set of
      coordinated responses as varying serum concentrations. Selection by serial rounds
      of high cell density or reduced serum concentration at low cell density results
      in progressive stages of field cancerization. Highly transformed cells
      proliferate in much lower concentrations of Mg(2+) and grow to much higher
      saturation densities than normal cells. It remains to be seen whether reduction
      in Mg(2+) in sparse, exponentially proliferating cultures selects for increases
      in saturation density and transformed foci. 

PMID- 25560237
TI  - Sequential cisplatin therapy and vaccination with HPV16 E6E7L2 fusion protein in
      saponin adjuvant GPI-0100 for the treatment of a model HPV16+ cancer.
AB  - Clinical studies suggest that responses to HPV16 E6E7L2 fusion protein (TA-CIN)
      vaccination alone are modest, and GPI-0100 is a well-tolerated, potent adjuvant.
      Here we sought to optimize both the immunogenicity of TA-CIN via formulation with
      GPI-0100 and treatment of HPV16+ cancer by vaccination after cisplatin
      chemotherapy. HPV16 neutralizing serum antibody titers, CD4+ T cell proliferative
      and E6/E7-specific CD8+ T cell responses were significantly enhanced when mice
      were vaccinated subcutaneously (s.c.) or intramuscularly (i.m.) with TA-CIN
      formulated with GPI-0100. Vaccination was tested for therapy of mice bearing
      syngeneic HPV16 E6/E7+ tumors (TC-1) either in the lung or subcutaneously. Mice
      treated with TA-CIN/GPI-0100 vaccination exhibited robust E7-specific CD8+ T cell
      responses, which were associated with reduced tumor burden in the lung, whereas
      mice receiving either component alone were similar to controls. Since vaccination
      alone was not sufficient for cure, mice bearing s.c. TC-1 tumor were first
      treated with two doses of cisplatin and then vaccinated. Vaccination with TA
      CIN/GPI-0100 i.m. substantially retarded tumor growth and extended survival after
      cisplatin therapy. Injection of TA-CIN alone, but not GPI-0100, into the tumor
      (i.t.) was similarly efficacious after cisplatin therapy, but the mice eventually
      succumbed. However, tumor regression and extended remission was observed in 80%
      of the mice treated with cisplatin and then intra-tumoral TA-CIN/GPI-0100
      vaccination. These mice also exhibited robust E7-specific CD8+ T cell and HPV16
      neutralizing antibody responses. Thus formulation of TA-CIN with GPI-0100 and
      intra-tumoral delivery after cisplatin treatment elicits potent therapeutic
      responses in a murine model of HPV16+ cancer. 

PMID- 25560239
TI  - Blood pressure, magnesium and other mineral balance in two rat models of salt
      sensitive, induced hypertension: effects of a non-peptide angiotensin II receptor
      type 1 antagonist.
AB  - The renin-angiotensin system is critically involved in regulating arterial blood
      pressure (BP). Inappropriate angiotensin type-1 receptor activation by
      angiotensin-II (Ang-II) is related to increased arterial BP. Mg has a role in BP;
      it can affect cardiac electrical activity, myocardial contractility, and vascular
      tone. To evaluate the relationship between high BP induced by a high sodium (Na)
      diet and Mg, and other mineral balances, two experimental rat models of salt
      sensitive, induced-hypertension were used: Ang-II infused and Dahl salt-sensitive
      (SS) rats. We found that: 1) Ang-II infusion progressively increased BP, which
      was accompanied by hypomagnesuria and signs of secondary hyperaldosteronism; 2)
      an additive effect between Ang-II and a high Na load may have an effect on
      strontium (Sr), zinc (Zn) and copper (Cu) balances; 3) Dahl SS rats fed a high Na
      diet had a slow pressor response, accompanied by altered Mg, Na, potassium (K),
      and phosphate (P) balances; and 4) losartan prevented BP increases induced by Ang
      II-NaCl, but did not modify mineral balances. In Dahl SS rats, losartan
      attenuated high BP and ameliorated magnesemia, Na and K balances. Mg metabolism
      maybe considered a possible defect in this strain of rat that may contribute to
      hypertension. 

PMID- 25560240
TI  - Effect of a natural mineral-rich water on catechol-O-methyltransferase function.
AB  - Catechol-O-methyltransferase (COMT) is a magnesium-dependent, catecholamine
      metabolizing enzyme, whose impaired activity has been positively associated with
      cardiovascular diseases, particularly hypertension. Consumption of some natural
      mineral-rich waters has been shown to exert protective effects on cardiovascular
      risk factors, eg. by decreasing arterial blood pressure and blood lipids.
      However, the molecular mechanisms underlying these effects are still poorly
      understood. So, the aim of this work was to investigate the effect of natural
      mineral-rich water ingestion upon liver and adrenal glands COMT expression and
      activity in Wistar Han rats. Over a seven-week period, animals had access to one
      of the following three drinking solutions: 1) tap water (control group; TW), 2)
      tap water with added Na(+) (to make the same concentration as in the MW group
      (TWNaCl group), or 3) natural mineral-rich water [Pedras Salgadas((r)), which is
      very rich in bicarbonate, and with higher sodium, calcium and magnesium content
      than control tap water (MW group)]. COMT expression and activity were determined
      by RT-PCR and HPLC-ED, respectively. A higher hepatic COMT activity was found in
      the MW group compared with the TW and TWNaCl groups. On the other hand, adrenal
      gland COMT mRNA expression decreased in the MW group compared to TW group. In
      conclusion, the ability of natural mineral-rich waters to increase hepatic COMT
      activity may eventually explain the positive cardiovascular effects associated
      with the consumption of some natural mineral-rich waters. 

PMID- 25560241
TI  - Combined inhibition of glycolysis, the pentose cycle, and thioredoxin metabolism
      selectively increases cytotoxicity and oxidative stress in human breast and
      prostate cancer.
AB  - Inhibition of glycolysis using 2-deoxy-d-glucose (2DG, 20mM, 24-48h) combined
      with inhibition of the pentose cycle using dehydroepiandrosterone (DHEA, 300uM,
      24-48h) increased clonogenic cell killing in both human prostate (PC-3 and DU145)
      and human breast (MDA-MB231) cancer cells via a mechanism involving thiol
      mediated oxidative stress. Surprisingly, when 2DG+DHEA treatment was combined
      with an inhibitor of glutathione (GSH) synthesis (l-buthionine sulfoximine; BSO,
      1mM) that depleted GSH>90% of control, no further increase in cell killing was
      observed during 48h exposures. In contrast, when an inhibitor of thioredoxin
      reductase (TrxR) activity (Auranofin; Au, 1uM), was combined with 2DG+DHEA or
      DHEA-alone for 24h, clonogenic cell killing was significantly increased in all
      three human cancer cell lines. Furthermore, enhanced clonogenic cell killing seen
      with the combination of DHEA+Au was nearly completely inhibited using the thiol
      antioxidant, N-acetylcysteine (NAC, 20mM). Redox Western blot analysis of PC-3
      cells also supported the conclusion that thioredoxin-1 (Trx-1) oxidation was
      enhanced by treatment DHEA+Au and inhibited by NAC. Importantly, normal human
      mammary epithelial cells (HMEC) were not as sensitive to 2DG, DHEA, and Au
      combinations as their cancer cell counterparts (MDA-MB-231). Overall, these
      results support the hypothesis that inhibition of glycolysis and pentose cycle
      activity, combined with inhibition of Trx metabolism, may provide a promising
      strategy for selectively sensitizing human cancer cells to oxidative stress
      induced cell killing. 

PMID- 25560242
TI  - "Twin peaks": searching for 4-hydroxynonenal urinary metabolites after oral
      administration in rats.
AB  - 4-Hydroxynonenal (HNE) is a cytotoxic and genotoxic lipid oxidation secondary
      product which is formed endogenously upon peroxidation of cellular n-6 fatty
      acids. However, it can also be formed in food or during digestion, upon
      peroxidation of dietary lipids. Several studies have evidenced that we are
      exposed through food to significant concentrations of HNE that could pose a
      toxicological concern. It is then of importance to known how HNE is metabolized
      after oral administration. Although its metabolism has been studied after
      intravenous administration in order to mimick endogenous formation, its in vivo
      fate after oral administration had never been studied. In order to identify and
      quantify urinary HNE metabolites after oral administration in rats, radioactive
      and stable isotopes of HNE were used and urine was analyzed by radio
      chromatography (radio-HPLC) and chromatography coupled with High Resolution Mass
      Spectrometry (HPLC-HRMS). Radioactivity distribution revealed that 48% of the
      administered radioactivity was excreted into urine and 15% into feces after 24h,
      while 3% were measured in intestinal contents and 2% in major organs, mostly in
      the liver. Urinary radio-HPLC profiles revealed 22 major peaks accounting for 88%
      of the urinary radioactivity. For identification purpose, HNE and its stable
      isotope [1,2-(13)C]-HNE were given at equimolar dose to be able to univocally
      identify HNE metabolites by tracking twin peaks on HPLC-HRMS spectra. The major
      peak was identified as 9-hydroxy-nonenoic acid (27% of the urinary radioactivity)
      followed by classical HNE mercapturic acid derivatives (the mercapturic acid
      conjugate of di-hydroxynonane (DHN-MA), the mercapturic acid conjugate of 4
      hydroxynonenoic acid (HNA-MA) in its opened and lactone form) and by metabolites
      that are oxidized in the terminal position. New urinary metabolites as thiomethyl
      and glucuronide conjugates were also evidenced. Some analyses were also performed
      on feces and gastro-intestinal contents, revealing the presence of tritiated
      water that could originate from beta-oxidation reactions. 

PMID- 25560243
TI  - Validation of protein carbonyl measurement: a multi-centre study.
AB  - Protein carbonyls are widely analysed as a measure of protein oxidation. Several
      different methods exist for their determination. A previous study had described
      orders of magnitude variance that existed when protein carbonyls were analysed in
      a single laboratory by ELISA using different commercial kits. We have further
      explored the potential causes of variance in carbonyl analysis in a ring study. A
      soluble protein fraction was prepared from rat liver and exposed to 0, 5 and
      15min of UV irradiation. Lyophilised preparations were distributed to six
      different laboratories that routinely undertook protein carbonyl analysis across
      Europe. ELISA and Western blotting techniques detected an increase in protein
      carbonyl formation between 0 and 5min of UV irradiation irrespective of method
      used. After irradiation for 15min, less oxidation was detected by half of the
      laboratories than after 5min irradiation. Three of the four ELISA carbonyl
      results fell within 95% confidence intervals. Likely errors in calculating
      absolute carbonyl values may be attributed to differences in standardisation. Out
      of up to 88 proteins identified as containing carbonyl groups after tryptic
      cleavage of irradiated and control liver proteins, only seven were common in all
      three liver preparations. Lysine and arginine residues modified by carbonyls are
      likely to be resistant to tryptic proteolysis. Use of a cocktail of proteases may
      increase the recovery of oxidised peptides. In conclusion, standardisation is
      critical for carbonyl analysis and heavily oxidised proteins may not be
      effectively analysed by any existing technique. 

PMID- 25560244
TI  - Steatosis-induced proteins adducts with lipid peroxidation products and nuclear
      electrophilic stress in hepatocytes.
AB  - Accumulating evidence suggests that fatty livers are particularly more
      susceptible to several pathological conditions, including hepatic inflammation,
      cirrhosis and liver cancer. However the exact mechanism of such susceptibility is
      still largely obscure. The current study aimed to elucidate the effect of
      hepatocytes lipid accumulation on the nuclear electrophilic stress. Accumulation
      of intracellular lipids was significantly increased in HepG2 cells incubated with
      fatty acid (FA) complex (1mM, 2:1 oleic and palmitic acids). In FA-treated cells,
      lipid droplets were localized around the nucleus and seemed to induce mechanical
      force, leading to the disruption of the nucleus morphology. Level of reactive
      oxygen species (ROS) was significantly increased in FA-loaded cells and was
      further augmented by treatment with moderate stressor (CoCl2). Increased ROS
      resulted in formation of reactive carbonyls (aldehydes and ketones, derived from
      lipid peroxidation) with a strong perinuclear accumulation. Mass-spectroscopy
      analysis indicated that lipid accumulation per-se can results in modification of
      nuclear protein by reactive lipid peroxidation products (oxoLPP). 235 Modified
      proteins involved in transcription regulation, splicing, protein synthesis and
      degradation, DNA repair and lipid metabolism were identified uniquely in FA
      treated cells. These findings suggest that steatosis can affect nuclear redox
      state, and induce modifications of nuclear proteins by reactive oxoLPP
      accumulated in the perinuclear space upon FA-treatment. 

PMID- 25560245
TI  - Human organic anion transporting polypeptide 1A2 (OATP1A2) mediates cellular
      uptake of all-trans-retinol in human retinal pigmented epithelial cells.
AB  - BACKGROUND AND PURPOSE: Vision depends on retinoid exchange between the retinal
      pigment epithelium (RPE) and photoreceptors. Defects in any step of the canonical
      visual cycle can lead to retinal degenerations. All-trans-retinol (atROL) plays
      an important role in visual signal transduction. However, how atROL enters human
      RPE from the apical membrane remains unclear. This study investigated the role of
      human organic anion transporting polypeptide 1A2 (OATP1A2) in atROL uptake in
      human RPE. EXPERIMENTAL APPROACH: Immunoblotting and immunostaining elucidated
      the expression and localization of OATP1A2 in human RPE. Transporter functional
      studies were conducted to assess the interaction of OATP1A2 with atROL. KEY
      RESULTS: Our study revealed OATP1A2 is expressed in human RPE, mainly at the
      apical membrane. Our data also indicated atROL inhibited the uptake of the
      typical OATP1A2 substrate, oestrone-3-sulfate (E3S), in over-expressing cells.
      Studies on the uptake of (3) H-atROL in these over-expressing cells revealed
      atROL is a substrate of OATP1A2. We confirmed these findings in human primary RPE
      cells. The transport of E3S and atROL was significantly reduced in human primary
      RPE cells with OATP1A2 siRNA silencing. CONCLUSION AND IMPLICATIONS: Our data
      provides the first evidence of OATP1A2 expression in human RPE and more
      importantly, its novel role in the cellular uptake of atROL, which might be
      essential to the proper functioning of the canonical visual cycle. Our findings
      contribute to the understanding of the molecular mechanisms involved in retinoid
      transport between the RPE and photoreceptors and provide novel insights into
      potential pharmaceutical interventions for visual cycle disruption associated
      with retinal degenerations.

PMID- 25560246
TI  - Age effects on cortical thickness in young Down's syndrome subjects: a cross
      sectional gender study.
AB  - INTRODUCTION: The aim of this study was to determine differences in the
      characteristic pattern of age-related cortical thinning in men and women with
      Down's syndrome (DS) by means of MRI and automatic cortical thickness
      measurements and a cross-sectional design, in a large cohort of young subjects.
      METHODS: Eighty-four subjects with DS, 30 females (11-35 years, mean age +/- SD =
      22.8 +/- 5.9) and 54 males (11-35 years, mean age +/- SD = 21.5 +/- 6.5), were
      examined using a 1.5-T scanner. MRI-based quantification of cortical thickness
      was performed using FreeSurfer software package. For all subjects participating
      in the study, the Pearson product-moment correlation coefficient between age and
      mean cortical thickness values has been evaluated. RESULTS: A significant
      negative correlation between cortical thickness and age was found in female DS
      subjects, predominantly in frontal and parietal lobes, bilaterally. In male DS
      subjects, a significant negative correlation between cortical thickness and age
      was found in the right fronto-temporal lobes and cingulate regions. Whole brain
      mean cortical thickness values were significantly negative correlated with age
      only in female DS subjects. CONCLUSIONS: Females with Down's syndrome showed a
      strong correlation between cortical thickness and age, already in early age. We
      suggest that the cognitive impairment due to hormonal deficit in the
      postmenopausal period could be emphasized by the early structural decline of gray
      matter in female DS subjects.

PMID- 25560247
TI  - Treatment and Follow-Up of Patients with Long-Gap Esophageal Atresia: 15 Years'
      of Experience from the Western Region of Sweden.
AB  - OBJECTIVE: This retrospective study aims to report treatment results in patients
      with long-gap esophageal atresia (LGEA), gross A + B type, and discuss the value
      of different clinical findings and physiological tests in the follow-up. METHODS:
      This retrospective observational study comprises all patients with LGEA admitted
      to our department between 1995 and 2010. RESULTS: A total of 16 patients were
      included. Their mean gestational age was 35(+2) weeks and their mean birth weight
      was 1,945 g (-2.5 standard deviation scores). No catch-up growth in height could
      be seen and they remained smaller than the average population during the study
      period. Gastrostomy was performed as the first surgical procedure. Overall, 11 of
      the 16 patients had a delayed primary anastomosis. Elongation of the distal
      esophageal segment was required in 3 of the 16 patients and a colonic
      interposition in 2 of the 16 patients. The median age at definitive surgery was
      150 days. All the patients had gastroesophageal reflux after their definitive
      surgery. Three of the 16 patients required surgery due to aspiration and all 3
      had a pathological lung clearance index (LCI) at multiple-breath washout (MBW).
      At the age of 1 or 7 years, the LCI was pathological in 4 of the 14 patients, and
      spirometry showed an obstruction in 9 of the 14 patients. CONCLUSION: LGEA is a
      severe congenital malformation, with severe morbidity. No mortality was seen. MBW
      could be a useful tool for the early detection of progressive pulmonary damage.

PMID- 25560248
TI  - Serum and Urinary Values of CA 19-9 and TGFbeta1 in a Rat Model of Partial or
      Complete Ureteral Obstruction.
AB  - INTRODUCTION: Abnormal levels of serum and urinary markers occur in the presence
      of renal damage associated to obstructive uropathy. Urinary and serum
      transforming growth factor beta 1 (TGFbeta1) and carbohydrate antigen (CA 19-9)
      have not yet been evaluated in an experimental model of obstructive uropathy.
      MATERIAL AND METHODS: Rats were divided into seven groups: reference, sham
      operation, unilateral nephrectomy, complete unilateral ureteral obstruction,
      partial unilateral ureteral obstruction, partial bilateral ureteral obstruction,
      and unilateral nephrectomy with contralateral partial ureteral obstruction.
      Kidney and ureter morphometry, TGFbeta1 and CA 19-9 serum and urinary
      concentrations and CA 19-9 renal tissue expression were analyzed. Correlation of
      these markers to complete, partial obstruction, or unobstructed groups was
      performed. RESULTS: Pathological findings correlated positively with the degree
      of ureteral obstruction, but negatively with urinary CA 19-9 levels. Marked
      underexpression of CA 19-9 was observed in kidneys with complete ureteral
      obstruction. No statistically significant differences were found for urinary and
      serum TGFbeta1 and also for serum CA 19-9. CONCLUSION: Urinary CA 19-9 correlated
      negatively with ureteral obstruction grade. Immunohistochemistry depicted CA 19-9
      expression on epithelial tubular cells cytoplasm, suggesting renal origin. Serum
      and urinary TGFbeta1 did not show alterations in response to severity and length
      of urinary obstruction, which might be associated with less intense renal
      remodeling.

PMID- 25560249
TI  - Best oxygenation index on day 1: a reliable marker for outcome and survival in
      infants with congenital diaphragmatic hernia.
AB  - AIM OF THE STUDY: Severe lung hypoplasia and persistent pulmonary hypertension
      are the main determining factors of survival in infants with congenital
      diaphragmatic hernia (CDH). The oxygenation index (ratio of delivered oxygen and
      its arterial level) closely reflects lung function. Single-institution studies
      have reported that best oxygenation index on day 1 of life (BOI-d1) is the most
      reliable postnatal predictor of survival in CDH. The aim of this study was to
      evaluate the predictive value of BOI-d1 in four disparate high volume centers in
      Europe. METHODS: A retrospective, multicenter study of infants with CDH born
      between 2000 and 2009 in four European tertiary institutions was conducted.
      Ethical approval was obtained from institutional review boards. Centers no. 1
      and. 4 offered extracorporeal membrane oxygenation (ECMO), whereas center no. 3
      offered fetal endoluminal tracheal occlusion (FETO) in fetuses defined as poor
      prognosis (lung-to-head ratio [LHR]<= 1.0 and "liver-up" position). Prenatal LHR
      and perinatal variables, including gestational age, birth weight, defect side,
      liver position, BOI-d1, and patch requirement, were analyzed. Receiver operating
      characteristic curves were used to determine cutoff values for continuous
      variables. Comparison was made between survivors and nonsurvivors using
      univariate analysis and logistic regression analysis, p<0.05 was considered
      significant. RESULTS: A total of 235 infants (center no. 1, n=29; no. 2, n=64;
      no. 3, n=113; and no. 4, n=29) were included. One infant required (2%) ECMO and
      66 (28%) had FETO. LHR was available in 83 patients (36%). Overall survival
      (discharge from hospital) and 28-day survival were 67.6% (n=159) and 72.3%
      (n=170), respectively. Univariate analysis showed that significant categorical
      predictors of 28-day survival were liver-down position (p<0.0001), LHR >1
      (p=0.003), and primary repair (p=0.02) but not defect side (p=0.83). Area under
      the receiver operating characteristic (AUROC) curve for continuous variables;
      gestational age, birth weight, and BOI-d1 were 0.70, 0.68, and 0.88,
      respectively. AUROC for BOI-d1 (28-day survival) was 0.91 and had sensitivities
      (73 and 91%) and specificities (92 and 80%) for cutoffs of 40 and 82,
      respectively. CONCLUSION: This multicenter study showed, that except from the
      defect side, all the prenatal variables studied have predictive value but the
      most useful is BOI-d1. This is simple to calculate and represents an excellent
      marker for lung function and a reliable early postnatal predictor of survival.

PMID- 25560251
TI  - Gastrointestinal stromal tumors (GISTs) at uncommon locations: a large population
      based analysis.
AB  - INTRODUCTION: Sparse information is available about GISTs in uncommon locations.
      Our large database analysis aims to determine the characteristics of GISTs in the
      esophagus, colon and rectum and compare to gastric GISTs. METHODS: The
      Surveillance Epidemiology and End Results (SEER) database was queried from 1990
      to 2009 using CS SCHEMA v0203. Characteristics of each location were compared to
      gastric GISTs. RESULTS: 4411 GIST (29 esophageal, 2658 stomach, 1463 small
      intestine, 126 colonic, and 135 rectal) from 1990 to 2009 were identified.
      Univariate and multivariate predictors of worse disease specific survival in both
      the entire cohort and surgical resection group include older age, male gender,
      tumor size > 5 cm, no surgical intervention and anatomical location. Although
      less likely to undergo surgical resection, esophageal GIST (all patients and
      resected) had a comparable survival to gastric GIST. A higher proportion of
      colonic GISTs presented with distant disease and had a worse disease specific
      survival when compared to rectal GISTs. CONCLUSION: Our results show a rising
      incidence in GISTs and highlight the characteristics of GISTs based on anatomical
      location. In addition, this is the first study to demonstrate that colonic GISTs
      behave differently when compared to rectal GISTs and warrants further prospective
      evaluation.

PMID- 25560252
TI  - A method to approximate the inverse of a part of the additive relationship
      matrix.
AB  - Single-step genomic predictions need the inverse of the part of the additive
      relationship matrix between genotyped animals (A22 ). Gains in computing time are
      feasible with an algorithm that sets up the sparsity pattern of A22-1 (SP
      algorithm) using pedigree searches, when A22-1 is close to sparse. The objective
      of this study is to present a modification of the SP algorithm (RSP algorithm)
      and to assess its use in approximating A22-1 when the actual A22-1 is dense. The
      RSP algorithm sets up a restricted sparsity pattern of A22-1 by limiting the
      pedigree search to a maximum number of searched branches. We have tested its use
      on four different simulated genotyped populations, from 10 000 to 75 000
      genotyped animals. Accuracy of approximation is tested by replacing the actual
      A22-1 by its approximation in an equivalent mixed model including only genotyped
      animals. Results show that limiting the pedigree search to four branches is
      enough to provide accurate approximations of A22-1, which contain approximately
      80% of zeros. Computing approximations is not expensive in time but may require a
      great amount of memory (at maximum, approximately 81 min and approximately 55 Gb
      of RAM for 75 000 genotyped animals using parallel processing on four threads). 

PMID- 25560250
TI  - A new score for the diagnosis of acute coronary syndrome in acute chest pain with
      non-diagnostic ECG and normal troponin.
AB  - BACKGROUND: Acute coronary syndrome (ACS) represents a difficult diagnostic
      challenge in patients with undifferentiated chest pain. There is a need for a
      valid clinical score to improve diagnostic accuracy. OBJECTIVES: To compare the
      performance of a model combining the Thrombolysis in Myocardial Infarction (TIMI)
      score and a score describing chest pain (ACS diagnostic score: ACSD score) with
      that of both scores alone in the diagnosis of ACS in ED patients with chest pain
      associated with a non-diagnostic ECG and normal troponin. METHODS: In this
      observational cohort study, we enrolled 809 patients admitted to a chest pain
      unit with normal ECG and normal troponin. They were prospectively evaluated in
      order to calculate TIMI score, chest pain characteristics score and ACSD score.
      Diagnosis of ACS was the primary outcome and defined on the basis of 2
      cardiologists after reviewing the patient medical records and follow-up data.
      Mortality and major cardiovascular events were followed for 1 month for patients
      discharged directly from ED. Discriminative power of scores was evaluated by the
      area under the ROC curve. RESULTS: ACS was confirmed in 90 patients (11.1%). The
      area under the ROC curve for ACSD score was 0.85 (95% CI 0.80 to 0.90) compared
      with 0.74 (95% CI 0.67 to 0.81) for TIMI and 0.79 (95% CI 0.74 to 0.84) for chest
      pain characteristics score. A threshold value of 9 appeared to optimise
      sensitivity (92%) and negative predictive value (99%) without excessively
      compromising specificity (62%) and positive predictive value (23%). CONCLUSIONS:
      The ACSD score showed a good discrimination performance and an excellent negative
      predictive value which allows safely ruling out ACS in ED patients with
      undifferentiated chest pain. Our findings should be validated in a larger
      multicentre study.

PMID- 25560253
TI  - Water extract of Cinnamomum cassia suppresses angiogenesis through inhibition of
      VEGF receptor 2 phosphorylation.
AB  - Angiogenesis, the process of new blood vessel formation, has been a major target
      for cancer therapy. Antiangiogenic herbal medicines are useful in the treatment
      of cancer. In this study, we found that a water extract of Cinnamomum cassia
      (CCWE) was a potent inhibitor of angiogenesis. In cultured human umbilical vein
      endothelial cells, CCWE suppressed vascular endothelial growth factor (VEGF)
      induced proliferation, migration, invasion, tube formation, and intracellular
      signaling events such as phosphorylation of ERK, p38 and VEGFR2, and activation
      of matrix metalloproteinase. Furthermore, CCWE inhibited VEGF-induced vessel
      sprouting of rat aorta ex vivo. These findings might be of particular interest
      for drug development because VEGF signaling is a potential target for treatment
      of angiogenesis-associated diseases. 

PMID- 25560254
TI  - Clonal dissemination of invasive and colonizing clonal complex 1 of serotype VI
      group B Streptococcus in central Taiwan.
AB  - BACKGROUND/PURPOSE: The aim of this study was to investigate clinical
      presentation, serotype distribution and genetic correlation of group B
      streptococcus (GBS) diseases. Since serotype VI prevalence far exceeded that
      reported in prior studies, genetic relationship of isolates was further analyzed.
      METHODS: GBS isolates obtaining from patients with invasive diseases and pregnant
      women with colonization between June 2007 and December 2010 were analyzed. All
      isolates were tested for serotypes by multiplex PCR assay and pulsed-field gel
      electrophoresis (PFGE). Serotype VI isolates were further analyzed by multilocus
      sequence typing (MLST). RESULTS: A total of 134 GBS isolates were recovered from
      blood of 126 patients with invasive disease (94.0%) and anogenital swabs of 8
      pregnant women (6.0%). Most common serotype was Ib (21.6%), followed by V
      (20.1%), VI (18.7%), III (15.7%), II (11.9 %), Ia (11.2%), and IX (0.7%).
      Serotype VI was also the leading type in infants with early onset disease (EOD;
      3/8, 37.5%) and colonizing pregnant women (3/8, 37.5%). PFGE distinguished 33
      pulsotypes, reflecting genetic diversity among GBS isolates. Among 25 serotype VI
      isolates tested, 14 were ST-1, seven were ST-679, three were ST-678, one was ST
      681, and distributed into four PFGE pulsotypes. ST-678, ST-679, and ST-681 were
      novel sequence types; ST-678 and ST-679 are single-locus variants of ST-1 that
      belongs to clonal complex (CC) 1. CONCLUSION: CC1 dissemination of serotype VI
      GBS thus emerges as an important invasive pathogen in infants and nonpregnant
      adults in central Taiwan. Serotype prevalence of GBS must be continuously
      monitored geographically to guide prevention strategy of GBS vaccines.

PMID- 25560255
TI  - NADf chip, a two-color microarray for simultaneous screening of multigene
      mutations associated with hearing impairment in North African Mediterranean
      countries.
AB  - Hearing impairment (HI) is the most frequent sensory defect. Genetic causes are
      involved in two thirds of prelingual cases. Moreover, the autosomal recessive HI
      frequency is increased in countries where there is a high rate of consanguinity,
      such as in North African Mediterranean countries. This population shares several
      features, including history and social behavior, that promote the spread of
      founder mutations. HI is characterized by tremendous heterogeneity in both the
      genetic and clinical aspects. The identification of the causal mutation is
      important for early diagnosis, clinical follow-up, and genetic counseling.
      Addressing the extreme genetic heterogeneity of HI using classic molecular
      methods would be expensive and time-consuming. We designed a cost-effective North
      African Deafness chip for rapid and simultaneous analysis of 58 mutations using
      multiplex PCR coupled with dual-color arrayed primer extension. These mutations
      are found in North African HI patients and are distributed over 31 exons and five
      introns in 21 distinct genes. Assay specificity was initially optimized using 103
      archived DNA samples of known genotypes. Blind validation of HI-unrelated
      patients revealed mutant alleles in 13 samples, and these mutations were
      confirmed by Sanger sequencing. The North African Deafness chip allows for
      simultaneous genotyping of eight different samples, at a minimal cost and in a
      single day, and is therefore amenable to large-scale molecular screening of HI in
      North Africa. 

PMID- 25560256
TI  - Interactions among mononitrophenol isomers during biodegradation of their
      mixtures.
AB  - Continuous aerobic biodegradation of 4-NP, 3-NP and 2-NP mixture was monitored in
      a packed bed reactor in simulated wastewater with a mixed microbial culture
      immobilized on expanded slate. Substrate loading was varied by increasing the
      concentration of one isomer while keeping the other two at constant levels, all
      at a constant residence time of 60 min. At large concentrations, all of the
      individual NP isomers suppressed the degradation rates of the other isomers at
      steady state; however, the observed patterns and threshold concentrations were
      different for all three substrates. As a result, conditions were determined for
      stable and efficient removal of NP mixtures. Changes of the biofilm composition
      during a long-term operation were identified. 

PMID- 25560257
TI  - Synthesis, morphology and antifungal activity of nano-particulated amphotericin
      B, ketoconazole and thymoquinone against Candida albicans yeasts and Candida
      biofilm.
AB  - In the current study, nano-particulated drugs-Amphotericin-B, Ketoconazole and
      Thymoquinone (an active ingredient of Nigella sativa)-were prepared using the
      ball milling technique, and their particle sizes were examined by transmission
      electron microscopy (TEM) and using a particle size analyzer. The grain sizes of
      the prepared compounds were found in between 5 to 20 nm, and exhibited quasi
      spherical morphology. The antifungal activity of each nano-particulated drug was
      investigated in vitro against Candida albicans yeasts and Candida biofilm, and
      compared with their micro-structured conventional forms. Nano-sized drugs were
      found to be two to four times more effective in disinfecting both the Candida
      yeasts and Candida biofilm. The study is a first of its kind as nano-forms of
      drugs have not been studied against Candida and Candida biofilm before. Further
      investigations are required for the determination of the clinical significance of
      the nano-formulation of antifungal substances.

PMID- 25560258
TI  - Solar photocatalytic degradation of chlorophenols mixture (4-CP and 2,4-DCP):
      Mechanism and kinetic modelling.
AB  - The solar-photocatalytic degradation mechanisms and kinetics of 4-chlorophenol (4
      CP) and 2,4-dichlorophenol (2,4-DCP) using TiO2 have been investigated both
      individually and combined. The individual solar-photocatalytic degradation of
      both phenolic compounds showed that the reaction rates follow pseudo-first-order
      reaction. During the individual photocatalytic degradation of both 4-CP and 2,4
      DCP under the same condition of TiO2 (0.5 g L(-1)) and light intensities (1000 mW
      cm(-2)) different intermediates were detected, three compounds associated with 4
      CP (hydroquinone (HQ), phenol (Ph) and 4-chlorocatechol (4-cCat)) and two
      compounds associated with 2,4-DCP (4-CP and Ph). The photocatalytic degradation
      of the combined mixture (4-CP and 2,4-DCP) was also investigated at the same
      conditions and different 2,4-DCP initial concentrations. The results showed that
      the degradation rate of 4-CP decreases when the 2,4-DCP concentration increases.
      Furthermore, the intermediates detected were similar to that found in the
      individual degradation but with high Ph concentration. Therefore, a possible
      reaction mechanism for degradation of this combined mixture was proposed.
      Moreover, a modified Langmuir-Hinshelwood (L-H) kinetic model considering all
      detected intermediates was developed. A good agreement between experimental and
      estimated results was achieved. This model can be useful for scaling-up purposes
      more accurately as its considering the intermediates formed, which has a
      significant effect on degrading the main pollutants (4-CP and 2,4-DCP).

PMID- 25560259
TI  - Comparison of metal lability in air-dried and fresh dewatered drinking water
      treatment residuals.
AB  - In this work, the labilities of Al, As, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn,
      Mo, Ni, Pb, Sr, V and Zn in air-dried (for 60 days) and fresh dewatered WTRs were
      compared using the Toxicity Characteristic Leaching Procedure (TCLP),
      fractionation, in vitro digestion and a plant enrichment test. The results showed
      that the air-dried and fresh dewatered WTRs had different properties, e.g.,
      organic matter composition and available nutrients. The air-dried and fresh
      dewatered WTRs were non-haf zardous according to the TCLP assessment method used
      in the United States; however, the metals in the two types of WTRs had different
      lability. Compared with the metals in the fresh dewatered WTRs, those in the air
      dried WTRs tended to be in more stable fractions and also exhibited lower
      bioaccessibility and bioavailability. Therefore, air-drying can decrease the
      metal lability and thereby reduce the potential metal pollution risk of WTRs.

PMID- 25560260
TI  - Estimation of the residual bromine concentration after disinfection of cooling
      water by statistical evaluation.
AB  - A statistical model based on multiple linear regression is developed, to estimate
      the bromine residual that can be expected after the bromination of cooling water.
      Make-up water sampled from a power plant in the Greek territory was used for the
      creation of the various cooling water matrices under investigation. The amount of
      bromine fed to the circuit, as well as other important operational parameters
      such as concentration at the cooling tower, temperature, organic load and contact
      time are taken as the independent variables. It is found that the highest
      contribution to the model's predictive ability comes from cooling water's organic
      load concentration, followed by the amount of bromine fed to the circuit, the
      water's mean temperature, the duration of the bromination period and finally its
      conductivity. Comparison of the model results with the experimental data confirms
      its ability to predict residual bromine given specific bromination conditions. 

PMID- 25560261
TI  - Removal of veterinary antibiotics, alkylphenolic compounds, and estrogens from
      the Wuluo constructed wetland in southern Taiwan.
AB  - This study investigated the treatment in the constructed Wuluo wetland, Taiwan,
      of 13 veterinary antibiotics, including five classes (tetracyclines,
      sulfonimides, chloramphenicol, fluoroquinolone, and dyes), five alkylphenolic
      compounds (nonylphenol di-ethoxylates [NP2EO], nonylphenol mono-ethoxylates
      [NP1EO], nonylphenol [NP], octylphenol [OP], and bisphenol A [BPA]), and three
      estrogens (17beta-estradiol [E2], estriol [E3], and 17alpha-ethynylestradiol
      [EE2]). The veterinary antibiotics oxytetracycline (OTC), ciprofloxacin (CIP),
      chloramphenicol (CAP), oxolinic acid (OXO), sulfamonomethoxine (SMM), and
      sulfadimethoxine (SDM) were detected in 7.1-96.4% of samples with concentrations
      varying widely from not detected to 552 ng/L. Removal efficiencies within
      different units of the wetland system exceeded 87% for OTC, CAP, SMM, and SDM,
      excluding those for IP and OXO, which were 72.1% and 43%, respectively. The other
      seven antibiotics (tetracycline [TC], enrofloxacin [ENR], chlortetracycline
      [CTC], sulfamerazine [SMR], sulfamethazine [SMZ], malachite green [MG], and
      leucomalachite green [LMG]) were all below detection limits in all samples.
      Additionally, detection rates were as follows: NP1EO, 70.0%; NP2EO, 70.0%; 4-n
      NP, 72.9%; 4-OP, 50.0%; BPA, 81.3%; E2, 52.1%; E3, 57.1%; and EE2, 31.3%.
      Concentrations of the alkylphenolic compounds were as follows: NP1EO, ND-1092.7;
      NP2EO, ND-643.7; 4-n-NP, ND-6812.3; 4-OP, ND-10400.1; and BPA, ND-1733 ng/L.
      Natural and synthetic estrogens E2, E3, and EE2 in samples were found in the
      ranges of ND-907.4, ND-749.5, and ND-226.0 ng/L, respectively. Analytical results
      show that with the exception of EE2 throughout the wetland system, target
      compounds were largely removed.

PMID- 25560262
TI  - Combined treatment of olive mill wastewater by Fenton's reagent and anaerobic
      biological process.
AB  - This work presents the application of Fenton's reagent process combined with
      anaerobic digestion to treat an olive mill wastewater (OMW). Firstly, OMW was pre
      treated by chemical oxidation in a batch reactor with Fenton's reagent, using a
      fixed H2O2/COD ratio of 0.20, pH = 3.5 and a H2O2/Fe(2+) molar ratio of 15:1.
      This advanced oxidation treatment allowed reaching reductions of 17.6 and 82.5%
      of chemical oxygen demand (COD) and total polyphenols (TP), respectively.
      Secondly, OMW treatment by anaerobic digestion was performed using previously
      adapted microorganisms immobilized in Sepiolite. These biological tests were
      carried out varying the substrate concentration supplied to the reactor and COD
      conversions from 52 to 74% were obtained. Afterwards, Fenton's reagent followed
      by anaerobic digestion was applied to OMW treatment. This combined process
      presented a significant improvement on organic load removal, reaching COD
      degradations from 64 to 88%. Beyond the pollutant load removal, it was also
      monitored the yield of methane generated throughout anaerobic experiments. The
      methane produced ranged from 281 cm(3) to 322 cm(3) of CH4/g COD removed.
      Additionally, a methane generation kinetic study was performed using the Monod
      Model. The application of this model allowed observing a kinetic constant
      increase of the combined process (kFN = 0.036 h(-1)) when compared to the single
      anaerobic process (kF = 0.017 h(-1)).

PMID- 25560263
TI  - Identification and quantification of bacteria and archaea responsible for ammonia
      oxidation in different activated sludge of full-scale wastewater treatment
      plants.
AB  - In this study, the abundance and sequences of the amoA gene in ammonia oxidizing
      bacteria (AOB) and ammonia oxidizing archaea (AOA) were defined in three
      wastewater treatment plants using activated sludge with biological nitrogen
      removal in different countries: Thailand, United States of America (USA), and
      Japan. Quantitative real-time polymerase chain reaction (PCR) and PCR coupled
      with denaturing gradient gel electrophoresis were used to find the comparative
      abundance and identity of AOB and AOA. The conditions at the Phuket WWTP in
      Thailand promoted the dominance of AOA amoA genes over AOB amoA genes, while
      conditions at the WWTPs in Japan and USA promoted growth of AOB. Three parameters
      that may have contributed to the AOA dominance in Phuket were longer SRT, higher
      temperature, and higher pH. The Phuket WWTP is a unique system that can be used
      to better understand the conditions that promote AOA growth and dominance over
      AOB. In addition, analysis of operational data in conjunction with AOA and AOB
      community structure from the Phuket WWTP may elucidate advantages of AOA in
      meeting stricter treatment standards. 

PMID- 25560264
TI  - Exploiting the efficacy of Lysinibacillus sp. RGS for decolorization and
      detoxification of industrial dyes, textile effluent and bioreactor studies.
AB  - Complete decolorization and detoxification of Reactive Orange 4 within 5 h (pH
      6.6, at 30 degrees C) by isolated Lysinibacillus sp. RGS was observed.
      Significant reduction in TOC (93%) and COD (90%) was indicative of conversion of
      complex dye into simple products, which were identified as naphthalene moieties
      by various analytical techniques (HPLC, FTIR, and GC-MS). Supplementation of
      agricultural waste extract considered as better option to make the process cost
      effective. Oxido-reductive enzymes were found to be involved in the degradation
      mechanism. Finally Loofa immobilized Lysinibacillus sp. cells in a fixed-bed
      bioreactor showed significant decolorization with reduction in TOC (51 and 64%)
      and COD (54 and 66%) for synthetic and textile effluent at 30 and 35 mL h(-1)
      feeding rate, respectively. The degraded metabolites showed non-toxic nature
      revealed by phytotoxicity and photosynthetic pigments content study for Sorghum
      vulgare and Phaseolus mungo. In addition nitrogen fixing and phosphate
      solubilizing microbes were less affected in treated wastewater and thus the
      treated effluent can be used for the irrigation purpose. This work could be
      useful for the development of efficient and ecofriendly technologies to reduce
      dye content in the wastewater to permissible levels at affordable cost.

PMID- 25560265
TI  - Effects of granular activated carbon on methane removal performance and
      methanotrophic community of a lab-scale bioreactor.
AB  - Two identical lab-scale bioreactor systems were operated to examine the effects
      of granular activated carbon (GAC) on methane removal performance and
      methanotrophic community. Both bioreactor systems removed methane completely at a
      CH4 loading rate of 71.2 g-CH4.d(-1) for 17 days. However, the methane removal
      efficiency declined to 88% in the bioreactor without GAC, while the bioreactor
      amended with GAC showed greater methane removal efficiency of 97% at a CH4
      loading rate of 107.5 g-CH4.d(-1). Although quantitative real-time PCR showed
      that methanotrophic populations were similar levels of 5-10 * 10(8) pmoA gene
      copy number.VSS(-1) in both systems, GAC addition changed the methanotrophic
      community composition of the bioreactor systems. Microarray assay revealed that
      GAC enhanced the type I methanotrophic genera including Methylobacter,
      Methylomicrobium, and Methylomonas of the system, which suggests that GAC
      probably provided a favorable environment for type I methanotrophs. These results
      indicated that GAC is a promising support material in bioreactor systems for CH4
      mitigation.

PMID- 25560266
TI  - Assessment of bacterial community structure in nitrifying biofilm under inorganic
      carbon-sufficient and -limited conditions.
AB  - In this work, nitrification and changes in the composition of the total bacterial
      community under inorganic carbon (IC)-limited conditions, in a nitrifying moving
      bed biofilm reactor, was investigated. A culture-independent analysis of cloning
      and sequencing based on the 16S rRNA gene was applied to quantify the bacterial
      diversity and to determine bacterial taxonomic assignment. IC concentrations had
      significant effects on the stability of ammonia-oxidation as indicated by the
      reduction of the nitrogen conversion rate with high NH4(+)-N loadings. The
      predominance of Nitrosomonas europaea was maintained in spite of changes in the
      IC concentration. In contrast, heterotrophic bacterial species contributed to a
      high bacterial diversity, and to a dynamic shift in the bacterial community
      structure, under IC-limited conditions. In this study, individual functions of
      heterotrophic bacteria were estimated based on taxonomic information. Possible
      key roles of coexisting heterotrophic bacteria are the assimilation of organic
      compounds of extracellular polymeric substances produced by nitrifiers, and
      biofilm formation by providing a filamentous structure and aggregation
      properties. 

PMID- 25560267
TI  - Combined ultrasonication and thermal pre-treatment of sewage sludge for
      increasing methane production.
AB  - This article focuses on the combination of ultrasonic and thermal treatment of
      sewage sludge (SS). The combination involved ultrasonicating a fraction of the
      sludge and thermal treatment at various temperatures and this resulted in
      solubilization of proteins and carbohydrates, and so contributing to increased
      COD solubilization. During the treatment, SCOD, soluble proteins and
      carbohydrates increased from 760 mg L(-1) to 10,200 mg L(-1), 110 mg L(-1) to
      2,900 mg L(-1) and 60 mg L(-1) to 630 mg L(-1), respectively. It was found
      ultrasonication of only a fraction of the sludge (>20%) followed by thermal
      treatment led to significant improvement compared to thermal and ULS treatments
      applied on their own. At 65 degrees C, the kinetic of solubilization was improved
      and the hyper-thermophilic treatment time could be reduced to a few hours when
      ultrasonication was used first. A linear correlation (R(2) = 95%) was found
      between the SCOD obtained after ultrasonication pre-treatment and anaerobic
      biodegradability. The combined treatment resulted in 20% increase in biogas
      production during the anaerobic digestion of the pre-treated sludge.

PMID- 25560268
TI  - High-performance microsupercapacitors based on two-dimensional graphene/manganese
      dioxide/silver nanowire ternary hybrid film.
AB  - Microsupercapacitors (MSCs), as one type of significant power source or energy
      storage unit in microelectronic devices, have attracted more and more attention.
      However, how to reasonably design electrode structures and exploit the active
      materials to endow the MSCs with excellent performances in a limited surface area
      still remains a challenge. Here, a reduced graphene oxide (RGO)/manganese dioxide
      (MnO2)/silver nanowire (AgNW) ternary hybrid film (RGMA ternary hybrid film) is
      successfully fabricated by a facile vacuum filtration and subsequent thermal
      reduction, and is used directly as a binder-free electrode for MSCs.
      Additionally, a flexible, transparent, all-solid state RMGA-MSC is also built,
      and its electrochemical performance in an ionic liquid gel electrolyte are
      investigated in depth. Notably, the RGMA-MSCs display superior electrochemical
      properties, including exceptionally high rate capability (up to 50000 mV.s(-1)),
      high frequency response (very short corresponding time constant tau0 = 0.14 ms),
      and excellent cycle stability (90.3% of the initial capacitance after 6000 cycles
      in ionic liquid gel electrolyte). Importantly, the electrochemical performance of
      RGMA-MSCs shows a strong dependence on the geometric parameters including the
      interspace between adjacent fingers and the width of the finger of MSCs. These
      encouraging results may not only provide important references for the design and
      fabrication of high-performance MSCs, but also make the RGMA ternary hybrid film
      promising for the next generation film lithium ion batteries and other energy
      storage devices. 

PMID- 25560269
TI  - A random forest model based classification scheme for neonatal amplitude
      integrated EEG.
AB  - BACKGROUND: Modern medical advances have greatly increased the survival rate of
      infants, while they remain in the higher risk group for neurological problems
      later in life. For the infants with encephalopathy or seizures, identification of
      the extent of brain injury is clinically challenging. Continuous amplitude
      integrated electroencephalography (aEEG) monitoring offers a possibility to
      directly monitor the brain functional state of the newborns over hours, and has
      seen an increasing application in neonatal intensive care units (NICUs). METHODS:
      This paper presents a novel combined feature set of aEEG and applies random
      forest (RF) method to classify aEEG tracings. To that end, a series of
      experiments were conducted on 282 aEEG tracing cases (209 normal and 73 abnormal
      ones). Basic features, statistic features and segmentation features were
      extracted from both the tracing as a whole and the segmented recordings, and then
      form a combined feature set. All the features were sent to a classifier
      afterwards. The significance of feature, the data segmentation, the optimization
      of RF parameters, and the problem of imbalanced datasets were examined through
      experiments. Experiments were also done to evaluate the performance of RF on aEEG
      signal classifying, compared with several other widely used classifiers including
      SVM-Linear, SVM-RBF, ANN, Decision Tree (DT), Logistic Regression(LR), ML, and
      LDA. RESULTS: The combined feature set can better characterize aEEG signals,
      compared with basic features, statistic features and segmentation features
      respectively. With the combined feature set, the proposed RF-based aEEG
      classification system achieved a correct rate of 92.52% and a high F1-score of
      95.26%. Among all of the seven classifiers examined in our work, the RF method
      got the highest correct rate, sensitivity, specificity, and F1-score, which means
      that RF outperforms all of the other classifiers considered here. The results
      show that the proposed RF-based aEEG classification system with the combined
      feature set is efficient and helpful to better detect the brain disorders in
      newborns.

PMID- 25560270
TI  - Towards clinical application of biomechanical tools for the prediction of
      fracture risk in metastatic bone disease.
AB  - Current clinical practice lacks an accurate predictor for the pathological
      fracture risk in metastatic bone disease, but biomechanical tools are under
      development to improve these predictions. In this paper we explain the
      limitations of currently used clinical guidelines and provide an overview of more
      objective and quantitative approaches that have been proposed for fracture risk
      assessment in metastatic bone disease. Currently, such mechanical models are as
      sensitive and specific as clinical guidelines, but there are a number of
      opportunities to further improve their predictive capacity. Hence, they are a
      promising tool to decrease the numbers of over- and undertreated patients. 

PMID- 25560271
TI  - A tissue adaptation model based on strain-dependent collagen degradation and
      contact-guided cell traction.
AB  - Soft biological tissues adapt their collagen network to the mechanical
      environment. Collagen remodeling and cell traction are both involved in this
      process. The present study presents a collagen adaptation model which includes
      strain-dependent collagen degradation and contact-guided cell traction. Cell
      traction is determined by the prevailing collagen structure and is assumed to
      strive for tensional homeostasis. In addition, collagen is assumed to
      mechanically fail if it is over-strained. Care is taken to use principally
      measurable and physiologically meaningful relationships. This model is
      implemented in a fibril-reinforced biphasic finite element model for soft
      hydrated tissues. The versatility and limitations of the model are demonstrated
      by corroborating the predicted transient and equilibrium collagen adaptation
      under distinct mechanical constraints against experimental observations from the
      literature. These experiments include overloading of pericardium explants until
      failure, static uniaxial and biaxial loading of cell-seeded gels in vitro and
      shortening of periosteum explants. In addition, remodeling under hypothetical
      conditions is explored to demonstrate how collagen might adapt to small
      differences in constraints. Typical aspects of all essentially different
      experimental conditions are captured quantitatively or qualitatively. Differences
      between predictions and experiments as well as new insights that emerge from the
      present simulations are discussed. This model is anticipated to evolve into a
      mechanistic description of collagen adaptation, which may assist in developing
      load-regimes for functional tissue engineered constructs, or may be employed to
      improve our understanding of the mechanisms behind physiological and pathological
      collagen remodeling. 

PMID- 25560272
TI  - A comparative study on complete and implant retained denture treatments: a
      biomechanics perspective.
AB  - Although implant-retained overdenture allows edentulous patients to take higher
      occlusal forces than the conventional complete dentures, the biomechanical
      influences have not been explored yet. Clinically, there is limited knowledge and
      means for predicting localized bone remodelling after denture treatment with and
      without implant support. By using finite element (FE) analysis, this article
      provides an in-silico approach to exploring the treatment effects on the oral
      mucosa and potential resorption of residual ridge under three different denture
      configurations in a patient-specific manner. Based on cone beam computerized
      tomography (CBCT) scans, a 3D heterogeneous FE model was created; and the
      supportive tissue, mucosa, was characterized as a hyperelastic material. A
      measured occlusal load (63N) was applied onto three virtual models, namely
      complete denture, two and four implant-retained overdentures. Clinically, the
      bone resorption was measured after one year in the two implant-retained
      overdenture treatment. Despite the improved stability and enhanced masticatory
      function, the implant-retained overdentures demonstrated higher hydrostatic
      stress in mucosa (43.6kPa and 39.9kPa for two and four implants) at the posterior
      ends of the mandible due to the cantilever effect, than the complete denture
      (33.4kPa). Hydrostatic pressure in the mucosa signifies a critical indicator and
      can be correlated with clinically measured bone resorption, pointing to severer
      mandibular ridge resorption posteriorly with implant-retained overdentures. This
      study provides a biomechanical basis for denture treatment planning to improve
      long-term outcomes with minimal residual ridge resorption. 

PMID- 25560273
TI  - Four decades of finite element analysis of orthopaedic devices: where are we now
      and what are the opportunities?
AB  - Finite element has been used for more than four decades to study and evaluate the
      mechanical behaviour total joint replacements. In Huiskes seminal paper "Failed
      innovation in total hip replacement: diagnosis and proposals for a cure", finite
      element modelling was one of the potential cures to avoid poorly performing
      designs reaching the market place. The size and sophistication of models has
      increased significantly since that paper and a range of techniques are available
      from predicting the initial mechanical environment through to advanced adaptive
      simulations including bone adaptation, tissue differentiation, damage
      accumulation and wear. However, are we any closer to FE becoming an effective
      screening tool for new devices? This review contains a critical analysis of
      currently available finite element modelling techniques including (i) development
      of the basic model, the application of appropriate material properties, loading
      and boundary conditions, (ii) describing the initial mechanical environment of
      the bone-implant system, (iii) capturing the time dependent behaviour in adaptive
      simulations, (iv) the design and implementation of computer based experiments and
      (v) determining suitable performance metrics. The development of the underlying
      tools and techniques appears to have plateaued and further advances appear to be
      limited either by a lack of data to populate the models or the need to better
      understand the fundamentals of the mechanical and biological processes. There has
      been progress in the design of computer based experiments. Historically, FE has
      been used in a similar way to in vitro tests, by running only a limited set of
      analyses, typically of a single bone segment or joint under idealised conditions.
      The power of finite element is the ability to run multiple simulations and
      explore the performance of a device under a variety of conditions. There has been
      increasing usage of design of experiments, probabilistic techniques and more
      recently population based modelling to account for patient and surgical
      variability. In order to have effective screening methods, we need to continue to
      develop these approaches to examine the behaviour and performance of total joint
      replacements and benchmark them for devices with known clinical performance.
      Finite element will increasingly be used in the design, development and pre
      clinical testing of total joint replacements. However, simulations must include
      holistic, closely corroborated, multi-domain analyses which account for real
      world variability. 

PMID- 25560274
TI  - Biglycan mediates suture expansion osteogenesis via potentiation of Wnt/beta
      catenin signaling.
AB  - Mechanical force across sutures is known to modulate suture osteogenesis.
      However, the underlying mechanisms still remain poorly understood. Biglycan is a
      component of extracellular matrix (ECM) that is postulated to release from ECM
      and function as a signaling molecule. Biglycan stimulates the bone formation
      through Wnt/beta-catenin signaling. To investigate the involvement of biglycan
      and Wnt/beta-catenin signaling in suture expansion osteogenesis, we observed the
      expansion force-induced response in mouse midpalatal suture expansion model in
      vivo, and the mechanical strain-induced response of Wnt/beta-catenin signaling in
      biglycan-deficient calvarial osteoblasts in vitro. Our data showed that expansion
      force significantly enhanced new bone formation at the edge of midpalatal
      sutures. Stronger biglycan positive staining was visible at the edge of expanding
      midpalatal sutures. The spatio-temporal expression of biglycan was highly
      consistent with ALP and COL-1, which also coincided with new bone formation
      throughout the midpalatal suture expansion process. Both protein and mRNA levels
      of biglycan, beta-catenin, and osteogenic markers including Runx2, ALP and COL-1
      were increased together. In addition, mechanical strain sufficiently induced
      upregulation of osteoblastic biglycan, which was paralleled with the strain
      induced potentiation of Wnt/beta-catenin signaling and Runx2 transcriptional
      activity. However, silencing osteoblastic biglycan resulted in an attenuated
      increase in the expression of nuclear active beta-catenin and Runx2 in response
      to mechanical strain. Our data demonstrated that biglycan as a component of ECM
      mediates suture expansion osteogenesis through the activation of Wnt/beta-catenin
      signaling. 

PMID- 25560275
TI  - Medical therapy for Cushing's disease: adrenal steroidogenesis inhibitors and
      glucocorticoid receptor blockers.
AB  - Morbidity and mortality in Cushing's disease (CD) patients are increased if
      patients are not appropriately treated. Surgery remains the first line therapy,
      however the role of medical therapy has become more prominent in patients when
      biochemical remission is not achieved/or recurs after surgery, while waiting
      effects of radiation therapy or when surgery is contraindicated. Furthermore, use
      of preoperative medical therapy has been also recognized. In addition to
      centrally acting therapies (reviewed elsewhere in this special issue), adrenal
      steroidogenesis inhibitors, and glucocorticoid receptor antagonists are
      frequently used. A PubMed search of all original articles or abstracts detailing
      medical therapy in CD, published within 12 months (2013-2014), were identified
      and pertinent data extracted. Although not prospectively studied, ketoconazole
      and metyrapone have been the most frequently used medical therapies. A large
      retrospective ketoconazole study showed that almost half of patients who
      continued on ketoconazole therapy achieved biochemical control and clinical
      improvement; however almost 20% discontinued ketoconazole due to poor
      tolerability. Notably, hepatotoxicity was usually mild and resolved after drug
      withdrawal. Etomidate remains the only drug available for intravenous use. A new
      potent inhibitor of both aldosterone synthase and 11beta-hydroxylase, following
      the completion of a phase II study LCI699 is being studied in a large phase III
      with promising results. Mifepristone, a glucocorticoid receptor antagonist, has
      been approved for hyperglycemia associated with Cushing's syndrome based on the
      results of a prospective study where it produced in the majority of patients'
      significant clinical and metabolic improvement. Absence of both a biochemical
      marker for remission and/or diagnosis of adrenal insufficiency remain, however, a
      limiting factor. Patient characteristics and preference should guide the choice
      between different medications in the absence of clinical trials comparing any of
      these therapies. Despite significant progress, there is still a need for a
      medical therapy that is more effective and with less adverse effects for patients
      with CD.

PMID- 25560276
TI  - Evaluating the relationship between education level and cognitive impairment with
      the Montreal Cognitive Assessment Test.
AB  - BACKGROUND: Mild cognitive impairment (MCI) is defined as 'a cognitive decline
      greater than that expected for an individual's age and education level but that
      does not interfere notably with activities of daily life'. The Montreal Cognitive
      Assessment (MoCA) is a screening test for MCI. METHODS: We investigated the
      performance of the Turkish version of the MoCA in detecting MCI among elderly
      persons in a rural area, the majority of whom have a low level of education. We
      evaluated 50 consecutive men referred from an outpatient clinic. Educational
      level was divided into three categories: group 1, less than primary (<5 years);
      group 2, primary (5 years); group 3, more than primary (>5 years). We evaluated
      the effect of education on MoCA scores and compared subjects' test performance
      among the different categories of education level. RESULTS: A total of 50 male
      patients with MCI (mean age: 70.74 +/- 7.87) met the inclusion criteria. There
      were no differences in the total scores based on education or in the subscores
      for visuospatial/executive function, naming, attention, abstraction and delayed
      recall. Language was the only domain that showed significant differences between
      the groups. In post-hoc analysis, differences were found between groups 1 and 3
      and between groups 1 and 2. Group 1 had significantly lower scores for language.
      The repeat subscore for language was significantly lower in group 1 than in group
      2. In fluency, there were significant differences between groups 2 and 3 and
      between group 1 and 3. CONCLUSION: To our knowledge, this is the first study to
      analyze the applicability of the Turkish version of MoCA in populations with
      little education. Our results emphasize the need to adapt the language sections
      of this test, so it can be easily used in populations with low education levels.

PMID- 25560278
TI  - Clinical experience with sunitinib dose escalation in metastatic renal cell
      carcinoma.
AB  - The oral multi-targeted tyrosine kinase inhibitor sunitinib malate is a standard
      first-line therapy in clear-cell metastatic renal cell carcinoma (mRCC).
      Sunitinib is usually administered daily for 4 weeks, followed by 2 weeks without
      treatment. Some patients experience worsening of disease symptoms during the
      treatment break. We report three cases of mRCC in whom continuous daily dosing
      and dose escalation were evaluated. In two cases, sunitinib was well tolerated at
      doses of 75 mg continuously and in all cases escalation of dose enabled regain of
      disease control. This suggests that continuous higher daily dosing of sunitinib
      is feasible and may provide additional clinical benefit for selected patients who
      experience minimal toxicity on the standard schedule. 

PMID- 25560277
TI  - Quantification of urinary TIMP-2 and IGFBP-7: an adequate diagnostic test to
      predict acute kidney injury after cardiac surgery?
AB  - INTRODUCTION: Postoperative acute kidney injury (AKI) is a frequently observed
      complication after on-pump cardiac surgery (CS) and is associated with adverse
      patient outcomes. Early identification of patients at risk is essential for the
      prevention of AKI after CS. In this study, we analysed whether urinary tissue
      inhibitor of metalloproteinase 2 (TIMP-2) combined with urine insulin-like growth
      factor binding protein 7 (IGFBP-7) ([TIMP-2] * [IGFBP-7]) is an adequate
      diagnostic test to identify early AKI after on-pump CS. METHODS: In 42 patients
      undergoing coronary artery bypass graft surgery, we surveyed individual risk
      factors for AKI and defined AKI by applying the Kidney Disease: Improving Global
      Outcomes (KDIGO) classification during the day of surgery and the following 2
      days after surgery. Concentrations of urinary TIMP-2 multiplied by IGFBP-7 were
      recorded at four time points: at baseline pre-surgery, at the end of surgery, 4
      hours after cardiopulmonary bypass (CPB) and at 8:00 AM on the first
      postoperative day. RESULTS: In total, 38% of the patients experienced AKI. The
      results showed a median baseline [TIMP-2] * [IGFBP-7] concentration of 0.3
      (ng/ml)(2)/1,000, decreasing at the end of surgery and then increasing at the
      next measurement point 4 hours after CPB and further on the first postoperative
      day. On the first postoperative day, patients with AKI had significantly higher
      concentrations of [TIMP-2] * [IGFBP-7]. On the day of surgery, the concentration
      did not significantly differ between patients classified as KDIGO 0 or KDIGO 1 or
      2. Previously published cutoff points of 0.3 and 2 were not confirmed in our
      study cohort. CONCLUSION: [TIMP-2] * [IGFBP-7] concentration can be used as a
      diagnostic test to identify patients at increased risk of AKI after CS on the
      first postoperative day. At earlier time points, no significant difference in
      [TIMP-2] * [IGFBP-7] concentration was found between patients classified as KDIGO
      0 or KDIGO 1 or 2. TRIAL REGISTRATION: German Clinical Trials Register (DRKS)
      DRKS00005457. Registered 26 November 2013.

PMID- 25560279
TI  - Malignancies in pemphigus and pemphigoid diseases.

PMID- 25560281
TI  - Selecting the primary efficacy outcome for the therapeutic hypothermia after
      pediatric cardiac arrest trials: a match made in heaven!

PMID- 25560280
TI  - p21-activated kinase 4 critically regulates melanogenesis via activation of the
      CREB/MITF and beta-catenin/MITF pathways.
AB  - p21-activated kinase 4 (PAK4) regulates a wide range of cellular events,
      including cytoskeletal remodeling, cell growth, and survival. Our previous study
      identified PAK4 as a key regulator of cAMP-response element-binding protein
      (CREB) that acts upstream of microphthalmia-associated transcription factor
      (MITF), a master transcription factor in melanogenesis. We therefore investigated
      the role of PAK4 in melanogenesis. Melanocytes express both PAK2 and PAK4
      isoforms, but only RNA interference knockdown of PAK4 significantly influenced
      alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanogenesis in B16
      melanoma cells. Consistent with this result, PAK4 inhibition by PF3758309, a
      potent ATP-competitive inhibitor of PAKs, suppressed not only alpha-MSH-induced
      melanogenesis in B16 melanoma and human epithelial melanocyte cells but also UVB
      induced melanogenesis in the skin of melanin-possessing hairless mice (HRM-2) in
      a dose-dependent manner. Inhibition of PAK4 over several days markedly decreased
      the levels of CREB, MITF, and tyrosinase in both HRM-2 mice and B16 melanoma
      cells. Moreover, PAK4 knockdown and inhibition suppressed alpha-MSH-stimulated
      beta-catenin phosphorylation at serine 675 (S675) but enhanced phosphorylation at
      S33/37, an indicator for ubiquitination-dependent proteolysis. Together, our
      results provide evidence that PAK4 promotes alpha-MSH/UVB-induced melanogenesis
      via the CREB and Wnt/beta-catenin signaling pathways and suggest that PAK4 may be
      a potential therapeutic target in pigmentation disorders. 

PMID- 25560282
TI  - Pediatric intensivists and elective procedural sedation: paradox or perfect pair?

PMID- 25560283
TI  - The autopsy: still valuable in the 21st century for identifying diagnostic
      errors.

PMID- 25560284
TI  - Pediatric cardiac surgery with cardiopulmonary bypass: a punch in the gut?

PMID- 25560285
TI  - Defining the boundaries of preload responsiveness at the bedside.

PMID- 25560286
TI  - Beyond adverse drug events and bloodstream infections: broadening the scope of
      harm events.

PMID- 25560287
TI  - Cardiac extracorporeal membrane oxygenation: dealing with what's left after
      cannulation.

PMID- 25560288
TI  - Monitoring of anticoagulation in extracorporeal membrane oxygenation: is anti-Xa
      the new activated clotting time?

PMID- 25560289
TI  - Cytopathic hypoxia and sepsis: is mitochondrial dysfunction pathophysiologically
      important or just an epiphenomenon.

PMID- 25560290
TI  - Pharmacokinetic reason for negative results of clonidine sedation in long-term
      ventilated neonates and infants.

PMID- 25560291
TI  - The authors reply.

PMID- 25560292
TI  - Compartmentalized interleukin-1beta in pulmonary secondary hemophagocytic
      lymphohistiocytosis.

PMID- 25560293
TI  - Transfusion strategies for single-ventricle palliation.

PMID- 25560294
TI  - The authors reply.

PMID- 25560296
TI  - Molecular basis of E. coli L-threonine aldolase catalytic inactivation at low pH.
AB  - L-Threonine aldolases (TAs), a family of enzymes belonging to the fold-type I
      pyridoxal 5'-phosphate (PLP) dependent enzymes, play a role in catalyzing the
      reversible cleavage of l-3-hydroxy-alpha-amino acids to glycine and the
      corresponding aldehydes. Threonine aldolases have great biotechnological
      potential for the syntheses of pharmaceutically relevant drug molecules because
      of their stereospecificity. The pH-dependency of their catalytic activity,
      affecting reaction intermediates, led us to study the effect of low-pH on
      Escherichia coli TA (eTA) structure. We report here a low-pH crystal structure of
      eTA at 2.1 A resolution, with a non-covalently bound uncleaved l-serine
      substrate, and a PLP cofactor bound as an internal aldimine. This structure
      contrasts with other eTA structures obtained at physiological pH that show
      products or substrates bound as PLP-external aldimines. The non-productive
      binding at low-pH is due to an unusual substrate serine binding orientation in
      which the alpha-amino group and carboxylate group are in the wrong positions
      (relative to the active site residues) as a result of protonation of the alpha
      amino group of the serine, as well as the active site histidines, His83 and
      His126. Protonation of these residues prevents the characteristic nucleophilic
      attack of the alpha-amino group of substrate serine on C4' of PLP to form the
      external aldimine. Our study shows that at low pH the change in charge
      distribution at the active site can result in substrates binding in a non
      productive orientation.

PMID- 25560297
TI  - AHNAK2 Participates in the Stress-Induced Nonclassical FGF1 Secretion Pathway.
AB  - FGF1 is a nonclassically released growth factor that regulates carcinogenesis,
      angiogenesis, and inflammation. In vitro and in vivo, FGF1 export is stimulated
      by cell stress. Upon stress, FGF1 is transported to the plasma membrane where it
      localizes prior to transmembrane translocation. To determine which proteins
      participate in the submembrane localization of FGF1 and its export, we used
      immunoprecipitation mass spectrometry to identify novel proteins that associate
      with FGF1 during heat shock. The heat shock-dependent association of FGF1 with
      the large protein AHNAK2 was observed. Heat shock induced the translocation of
      FGF1 and AHNAK2 to the cytoskeletal fraction. In heat-shocked cells, FGF1 and the
      C-terminal fragment of AHNAK2 colocalized with F-actin in the vicinity of the
      cell membrane. Depletion of AHNAK2 resulted in a drastic decrease of stress
      induced FGF1 export but did not affect spontaneous FGF2 export and FGF1 release
      induced by the inhibition of Notch signaling. Thus, AHNAK2 is an important
      element of the FGF1 nonclassical export pathway.

PMID- 25560299
TI  - Editorial.

PMID- 25560298
TI  - Functional contributions and interactions between the human hippocampus and
      subregions of the striatum during arbitrary associative learning and memory.
AB  - The hippocampus and striatum are thought to have different functional roles in
      learning and memory. It is unknown under what experimental conditions their
      contributions are dissimilar or converge, and the extent to which they interact
      over the course of learning. In order to evaluate both the functional
      contributions of as well as the interactions between the human hippocampus and
      striatum, the present study used high-resolution functional magnetic resonance
      imaging (fMRI) and variations of a conditional visuomotor associative learning
      task that either taxed arbitrary associative learning (Experiment 1) or stimulus
      response learning (Experiment 2). In the first experiment, we observed changes in
      activity in the hippocampus and anterior caudate that reflect differences between
      the two regions consistent with distinct computational principles. In the second
      experiment, we observed activity in the putamen that reflected content specific
      representations during the learning of arbitrary conditional visuomotor
      associations. In both experiments, the hippocampus and ventral striatum
      demonstrated dynamic functional coupling during the learning of new arbitrary
      associations, but not during retrieval of well-learned arbitrary associations
      using control variants of the tasks that did not preferentially tax one system
      versus the other. These findings suggest that both the hippocampus and subregions
      of the dorsal striatum contribute uniquely to the learning of arbitrary
      associations while the hippocampus and ventral striatum interact over the course
      of learning.

PMID- 25560300
TI  - The role of genetic variation across IL-1beta, IL-2, IL-6, and BDNF in
      antipsychotic-induced weight gain.
AB  - OBJECTIVES: Antipsychotics with high weight gain-inducing propensities influence
      the expression of immune and neurotrophin genes, which have been independently
      related to obesity indices. Thus, we investigated whether variants in the genes
      encoding interleukin (IL)-1beta, IL-2, and IL-6 and brain-derived neurotrophic
      factor (BDNF) Val66Met are associated with antipsychotic-induced weight gain
      (AIWG). METHODS: Nineteen polymorphisms were genotyped using Taqman((r)) assays
      in 188 schizophrenia patients on antipsychotic treatment for up to 14 weeks. Mean
      weight change (%) from baseline was compared across genotypic groups using
      analysis of covariance (ANCOVA). Epistatic effects between cytokine polymorphisms
      and BDNF Val66Met were tested using Model-Based Multifactor Dimensionality
      Reduction. RESULTS: In European patients, IL-1beta rs16944*GA (P = 0.013,
      Pcorrected = 0.182), IL-1beta rs1143634*G (P = 0.001, Pcorrected = 0.014), and
      BDNF Val66Met (Val/Val, P = 0.004, Pcorrected = 0.056) were associated with
      greater AIWG, as were IL-1beta rs4849127*A (P = 0.049, Pcorrected = 0.784), and
      IL-1beta rs16944*GA (P = 0.012, Pcorrected = 0.192) in African Americans. BDNF
      Val66Met interacted with both IL-1beta rs13032029 (Val/Met+ TT, PPerm = 0.029),
      and IL-6 rs2069837 (Val/Val+ AA, PPerm = 0.021) in Europeans, in addition to IL
      1beta rs16944 (Val/Val+ GA, PPerm = 0.006) in African Americans. CONCLUSIONS:
      SNPs across IL-1beta and BDNF Val66Met may influence AIWG. Replication of these
      findings in larger, independent samples is warranted.

PMID- 25560301
TI  - Inhibitory effects of lithium chloride on replication of type II porcine
      reproductive and respiratory syndrome virus in vitro.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the
      most serious diseases affecting the swine industry worldwide; however, there are
      no efficient control strategies against PRRS virus (PRRSV) at present. Therefore,
      development of new antiviral treatment strategies is urgently needed. As
      reported, lithium chloride (LiCl) can efficiently impair the replication of a
      variety of viruses, including infectious bronchitis coronavirus (IBV) and
      transmissible gastroenteritis coronavirus (TGEV). In this report, we explored
      whether LiCl had the potential to inhibit PRRSV infection. METHODS: MARC-145
      cells were treated with LiCl at various stages of PRRSV life cycle. Virus
      titration assay was performed to determine the virus infectivity. The expression
      of viral mRNA and protein was measured by real-time PCR and indirect
      immunofluorescence assay, respectively. The transcript levels of cytokines were
      evaluated by real-time PCR. RESULTS: LiCl significantly suppressed the synthesis
      of viral RNA and protein; however, it did not block PRRSV binding and entry.
      Further studies confirmed that LiCl inhibited PRRSV replication at an early stage
      and TNF-alpha, an antiviral cytokine, was significantly increased after LiCl
      treatment. Thus, we suggested that LiCl inhibited PRRSV infection by up
      regulating the level of antiviral cytokine TNF-alpha at an early infection stage.
      CONCLUSIONS: Our findings imply that the LiCl has the potential to be used as
      anti-PRRSV therapy.

PMID- 25560302
TI  - Energy drinks and their adverse health effects: A systematic review of the
      current evidence.
AB  - PURPOSE: With the rising consumption of so-called energy drinks over the last few
      years, there has been a growing body of literature describing significant adverse
      health events after the ingestion of these beverages. To gain further insight
      about the clinical spectrum of these adverse events, we conducted a literature
      review. METHODS: Using PubMed and Google-Scholar, we searched the literature from
      January 1980 through May 2014 for articles on the adverse health effects of
      energy drinks. A total of 2097 publications were found. We then excluded
      molecular and industry-related studies, popular media reports, and case reports
      of isolated caffeine toxicity, yielding 43 reports. CONCLUSION: Energy drink
      consumption is a health issue primarily of the adolescent and young adult male
      population. It is linked to increased substance abuse and risk-taking behaviors.
      The most common adverse events affect the cardiovascular and neurological
      systems. The most common ingredient in energy drinks is caffeine, and it is
      believed that the adverse events are related to its effects, as well as
      potentiating effects of other stimulants in these drinks. Education, regulation,
      and further studies are required.

PMID- 25560303
TI  - TGF-beta1 up-regulates connexin43 expression: a potential mechanism for human
      trophoblast cell differentiation.
AB  - Connexin43 (Cx43)-mediated gap junctional intercellular communication (GJIC) are
      required for human trophoblast differentiation. To date, whether Cx43 mediates
      TGF-beta1-induced trophoblast differentiation has not been determined. We showed
      that treatment with TGF-beta1 increased Cx43 expression and GJIC in HTR-8/SVneo
      human trophoblast cells. In addition, Smad and ERK1/2 signaling pathways were
      involved in TGF-beta1-induced up-regulation of Cx43. Moreover, TGF-beta1
      increased the expression of the syncytiotrophoblast marker, beta-hCG.
      Importantly, knockdown of Cx43 abolished the TGF-beta1-induced up-regulation of
      beta-hCG. Furthermore, overexpression of Cx43 up-regulated beta-hCG expression.
      These results provide evidence that Cx43 and GJIC activity are up-regulated by
      TGF-beta1 in human trophoblast cells, which subsequently contributes to TGF-beta1
      induced trophoblast differentiation.

PMID- 25560304
TI  - Correction to "a new tetracyclic lactam building block for thick, broad-bandgap
      photovoltaics".

PMID- 25560306
TI  - Known susceptibility SNPs for sporadic prostate cancer show a similar association
      with "hereditary" prostate cancer.
AB  - BACKGROUND: More than 70 single nucleotide polymorphisms (SNPs) have been
      reported to be associated with prostate cancer (PC) risk; these were mainly
      identified in the general population with predominantly sporadic PC (SPC).
      Previous studies have suggested similar associations between a selection of these
      SNPs and hereditary PC (HPC). Our aim was to evaluate the effect of all known PC
      risk SNPs and their discriminative value for SPC and HPC. METHODS: Seventy-four
      PC susceptibility SNPs (reported in literature up to June 2014) were genotyped in
      a population-based series of 620 SPC patients, 312 HPC patients from the national
      Dutch registry and 1819 population-based referents. Association analyses were
      performed using logistic regression, focusing on directional consistency of the
      odds ratios (ORs) with those in the original reports, that is, whether the OR was
      in the same direction as in the original report. Discriminative performance was
      evaluated by a genetic risk score used in logistic regression and receiver
      operating characteristic (ROC) curve analyses. RESULTS: Directional consistency
      was seen for 62 SNPs in SPC and 64 SNPs in HPC, 56 of which overlapped. ORs were
      mostly higher for HPC with 22 ORs >1.25 versus 5 for SPC. Discriminative
      performance was better for HPC with an area under the ROC curve of 0.73 versus
      0.64 for SPC. CONCLUSIONS: A large overlap was found for the associations between
      low-penetrance susceptibility SNPs and SPC and HPC, suggesting a similarity in
      genetic etiology. This warrants a reconsideration of "HPC" and a restrictive
      policy toward prostate-specific antigen testing in men with a positive family
      history. Genetic risk scores might be used for PC risk stratification on the
      population level.

PMID- 25560305
TI  - Imaging complex protein metabolism in live organisms by stimulated Raman
      scattering microscopy with isotope labeling.
AB  - Protein metabolism, consisting of both synthesis and degradation, is highly
      complex, playing an indispensable regulatory role throughout physiological and
      pathological processes. Over recent decades, extensive efforts, using approaches
      such as autoradiography, mass spectrometry, and fluorescence microscopy, have
      been devoted to the study of protein metabolism. However, noninvasive and global
      visualization of protein metabolism has proven to be highly challenging,
      especially in live systems. Recently, stimulated Raman scattering (SRS)
      microscopy coupled with metabolic labeling of deuterated amino acids (D-AAs) was
      demonstrated for use in imaging newly synthesized proteins in cultured cell
      lines. Herein, we significantly generalize this notion to develop a comprehensive
      labeling and imaging platform for live visualization of complex protein
      metabolism, including synthesis, degradation, and pulse-chase analysis of two
      temporally defined populations. First, the deuterium labeling efficiency was
      optimized, allowing time-lapse imaging of protein synthesis dynamics within
      individual live cells with high spatial-temporal resolution. Second, by tracking
      the methyl group (CH3) distribution attributed to pre-existing proteins, this
      platform also enables us to map protein degradation inside live cells. Third,
      using two subsets of structurally and spectroscopically distinct D-AAs, we
      achieved two-color pulse-chase imaging, as demonstrated by observing aggregate
      formation of mutant hungtingtin proteins. Finally, going beyond simple cell
      lines, we demonstrated the imaging ability of protein synthesis in brain tissues,
      zebrafish, and mice in vivo. Hence, the presented labeling and imaging platform
      would be a valuable tool to study complex protein metabolism with high
      sensitivity, resolution, and biocompatibility for a broad spectrum of systems
      ranging from cells to model animals and possibly to humans. 

PMID- 25560308
TI  - Lactoferrin- and antitransferrin-modified liposomes for brain targeting of the
      NK3 receptor agonist senktide: preparation and in vivo evaluation.
AB  - The aim of this work was to evaluate the capability of lactoferrin- and
      antitransferrin-modified long circulating liposomes to deliver the hydrophilic
      peptide senktide, a selective NK3 receptor agonist unable to cross the blood
      brain barrier, to central nervous system by using an indirect method based on in
      vivo microdialysis studies to estimate the responsiveness of nucleus accumbens
      shell dopamine to senktide. To this purpose, senktide was encapsulated in
      different targeted and not-targeted stealth liposomes prepared using film
      hydration method. Formulations were characterized in terms of morphology, size
      distribution, zeta potential, encapsulation efficiency, and antibody presence on
      the liposome surface. In vivo microdialysis studies were performed injecting
      intravenously the senktide-loaded liposomes and comparing obtained dopamine
      levels with those found with the free senktide given intracerebroventricularly.
      Results showed that all vesicles were spherical, small in size (around 120 nm),
      homogeneously dispersed, and slightly negatively charged. TEM analysis, using an
      anti IgG secondary antibody with 10nm gold nanoparticles at its distal end,
      demonstrated the successful linkage of the antibody on the liposomal surface.
      Intravenously administered in rats, senktide-loaded targeted stealth liposomes
      elicited a significant increase of dialysate dopamine in the nucleus accumbens
      shell, which was comparable to that of the free senktide given
      intracerebroventricularly when antitransferrin-targeted liposomes were tested. On
      the contrary, control stealth liposomes did not affect dopamine levels. Senktide
      brain levels were higher using the antitransferrin-targeted liposomes in
      comparison with the lactoferrin ones, while the opposite was obtained in the
      liver tissue where the highest senktide accumulation was always found.

PMID- 25560309
TI  - Targeting delivery of etoposide to inhibit the growth of human glioblastoma
      multiforme using lactoferrin- and folic acid-grafted poly(lactide-co-glycolide)
      nanoparticles.
AB  - Lactoferrin (Lf) and folic acid (FA) were crosslinked on poly(lactide-co
      glycolide) (PLGA) nanoparticles (NPs) for transporting etoposide across the blood
      brain barrier (BBB) and treating human brain malignant glioblastoma. Lf- and FA
      grafted PLGA NPs (Lf/FA/PLGA NPs) were employed to permeate the monolayer of
      human brain-microvascular endothelial cells (HBMECs) regulated by human
      astrocytes and to inhibit the multiplication of U87MG cells. Lf/FA/PLGA NPs
      showed a satisfactory entrapment efficiency of etoposide and characteristics of
      sustained drug release. When compared with PLGA NPs, the permeability coefficient
      for etoposide across the BBB using Lf/FA/PLGA NPs increased about twofold. The
      antiproliferative efficacy against the growth of U87MG cells was in the following
      order: Lf/FA/PLGA NPs>FA/PLGA NPs>PLGA NPs>free etoposide solution. In addition,
      the targeting ability of Lf/FA/PLGA NPs was evidenced by immunostaining of Lf
      receptor on HBMECs and folate receptor on U87MG cells during endocytosis.
      Lf/FA/PLGA NPs with loaded etoposide can be a promising anticancer
      pharmacotherapy to enhance the delivery of etoposide to malignant brain tumors
      for preclinical trials. 

PMID- 25560310
TI  - Autophagy contributes to regulation of nuclear dynamics during vegetative growth
      and hyphal fusion in Fusarium oxysporum.
AB  - In the fungal pathogen Fusarium oxysporum, vegetative hyphal fusion triggers
      nuclear mitotic division in the invading hypha followed by migration of a nucleus
      into the receptor hypha and degradation of the resident nucleus. Here we examined
      the role of autophagy in fusion-induced nuclear degradation. A search of the F.
      oxysporum genome database for autophagy pathway components identified putative
      orthologs of 16 core autophagy-related (ATG) genes in yeast, including the
      ubiquitin-like protein Atg8, which is required for the formation of
      autophagosomal membranes. F. oxysporum Foatg8Delta mutants were generated in a
      strain harboring H1-cherry fluorescent protein (ChFP)-labeled nuclei to
      facilitate analysis of nuclear dynamics. The Foatg8Delta mutants did not show MDC
      positive staining in contrast to the wild type and the FoATG8-complemented
      (cFoATG8) strain, suggesting that FoAtg8 is required for autophagy in F.
      oxysporum. The Foatg8Delta strains displayed reduced rates of hyphal growth,
      conidiation, and fusion, and were significantly attenuated in virulence on tomato
      plants and in the nonvertebrate animal host Galleria mellonella. In contrast to
      wild-type hyphae, which are almost exclusively composed of uninucleated hyphal
      compartments, the hyphae of the Foatg8Delta mutants contained a significant
      fraction of hyphal compartments with 2 or more nuclei. The increase in the number
      of nuclei per hyphal compartment was particularly evident after hyphal fusion
      events. Time-lapse microscopy analyses revealed abnormal mitotic patterns during
      vegetative growth in the Foatg8Delta mutants. Our results suggest that autophagy
      mediates nuclear degradation after hyphal fusion and has a general function in
      the control of nuclear distribution in F. oxysporum. 

PMID- 25560311
TI  - Congenital blindness affects diencephalic but not mesencephalic structures in the
      human brain.
AB  - While there is ample evidence that the structure and function of visual cortical
      areas are affected by early visual deprivation, little is known of how early
      blindness modifies subcortical relay and association thalamic nuclei, as well as
      mesencephalic structures. Therefore, in the present multicenter study, we used
      MRI to measure volume of the superior and inferior colliculi, as well as of the
      thalamic nuclei relaying sensory and motor information to the neocortex,
      parcellated according to atlas-based thalamo-cortical connections, in 29
      individuals with congenital blindness of peripheral origin (17 M, age 35.7 +/-
      14.3 years) and 29 sighted subjects (17 M, age 31.9 +/- 9.0). Blind participants
      showed an overall volume reduction in the left (p = 0.008) and right (p = 0.007)
      thalami, as compared to the sighted individuals. Specifically, the lateral
      geniculate (i.e., primary visual thalamic relay nucleus) was 40% reduced (left: p
      = 4 * 10(-6), right: p < 1 * 10(-6)), consistent with findings from animal
      studies. In addition, associated thalamic nuclei that project to temporal (left:
      p = 0.005, right: p = 0.005), prefrontal (left: p = 0.010, right: p = 0.014),
      occipital (left: p = 0.005, right: p = 0.023), and right premotor (p = 0.024)
      cortical regions were also significantly reduced in the congenitally blind group.
      Conversely, volumes of the relay nuclei directly involved in auditory, motor, and
      somatosensory processing were not affected by visual deprivation. In contrast, no
      difference in volume was observed in either the superior or the inferior
      colliculus between the two groups. Our findings indicate that visual loss since
      birth leads to selective volumetric changes within diencephalic, but not
      mesencephalic, structures. Both changes in reciprocal cortico-thalamic
      connections or modifications in the intrinsic connectivity between relay and
      association nuclei of the thalamus may contribute to explain these alterations in
      thalamic volumes. Sparing of the superior colliculi is in line with their
      composite, multisensory projections, and with their not exclusive visual nature.

PMID- 25560312
TI  - Primary mammary carcinoma in a Sika deer (Cervus Nippon) with a coexisting
      intestinal adenocarcinoma.

PMID- 25560313
TI  - A new ellagic acid derivative from Polygonum runcinatum.
AB  - A new ellagic acid derivative, 3,3'-dimethylellagic acid-4'-O-(6"-galloyl)-beta-D
      glucoside, named runcinatside (5), together with four known compounds 3,3'
      dimethylellagic acid (1), 3,3',4'-trimethylellagic acid (2), 3,3'-dimethylellagic
      acid-4'-O-beta-D-glucoside (3) and 3-methylellagic acid-4'-O-alpha-L-rhamno
      pyranoside (4), was isolated from the roots of Polygonum runcinatum Buch.-Ham. ex
      D.Don Var. sinense Hemsl and the structures of these compounds were established
      by spectroscopic methods and comparison with previously reported data. All
      compounds showed antioxidant activities in vitro and compound 5 possessed the
      highest activity.

PMID- 25560314
TI  - Capsule commentary on Kantor et al. Pending studies at hospital discharge: a pre
      post analysis of an electronic medical record tool to improve communication at
      hospital discharge.

PMID- 25560315
TI  - Improvement happens: team-based primary care, an interview with Stuart Pollack.

PMID- 25560317
TI  - Maintaining competence in general internal medicine.

PMID- 25560316
TI  - Electronic health records and transgender patients--practical recommendations for
      the collection of gender identity data.
AB  - Transgender (Trans, Trans*) persons may have a gender identity and a preferred
      name that differ from those assigned at birth, and/or those listed on their
      current legal identification (Gender ID, Birth-assigned Sex, Legal Sex).
      Transgender people who are referred to in a clinical setting using the wrong
      pronoun or name may suffer distress, ridicule or even assault by others in the
      waiting area, and may not return for further care. Furthermore, failure to
      accurately document (and therefore count) transgender identities has negative
      implications on quality improvement and research efforts, funding priorities and
      policy activities. The recent announcement that gender identity data may be
      included in Meaningful Use Stage 3 has accelerated the need for guidance for both
      vendors and local implementation teams on how to best record and store these
      data. A recent study demonstrated wide variation in current practices. This
      manuscript provides a description of identifiers associated with gender identity,
      and makes practical and evidence based recommendations for implementation and
      front-end functionality. 

PMID- 25560318
TI  - Capsule commentary on Napoles et. al, Physician counseling on colorectal cancer
      screening and receipt of screening among Latino patients.

PMID- 25560319
TI  - Randomized trial of a health IT tool to support between-visit-based laboratory
      monitoring for chronic disease medication prescriptions.
AB  - BACKGROUND: Lack of timely medication intensification and inadequate medication
      safety monitoring are two prevalent and potentially modifiable barriers to
      effective and safe chronic care. Innovative applications of health information
      technology tools may help support chronic disease management. OBJECTIVE: To
      examine the clinical impact of a novel health IT tool designed to facilitate
      between-visit ordering and tracking of future laboratory testing. DESIGN AND
      PARTICIPANTS: Clinical trial randomized at the provider level (n = 44 primary
      care physicians); patient-level outcomes among 3,655 primary care patients
      prescribed 5,454 oral medicines for hyperlipidemia, diabetes, and/or hypertension
      management over a 12-month period. MAIN MEASURES: Time from prescription to
      corresponding follow-up laboratory testing; proportion of follow-up time that
      patients achieved corresponding risk factor control (A1c, LDL); adverse event
      laboratory monitoring 4 weeks after medicine prescription. KEY RESULTS: Patients
      whose physicians were allocated to the intervention (n = 1,143) had earlier LDL
      laboratory assessment compared to similar patients (n = 703) of control
      physicians [adjusted hazard ratio (aHR): 1.15 (1.01-1.32), p = 0.04]. Among
      patients with elevated LDL (486 intervention, 324 control), there was decreased
      time to LDL goal in the intervention group [aHR 1.26 (0.99-1.62)]. However,
      overall there were no significant differences between study arms in time spent at
      LDL or HbA1c goal. Follow-up safety monitoring (e.g., creatinine, potassium, or
      transaminases) was relatively infrequent (ranging from 7 % to 29 % at 4 weeks)
      and not statistically different between arms. Intervention physicians indicated
      that lack of reimbursement for non-visit-based care was a barrier to use of the
      tool. CONCLUSIONS: A health IT tool to support between-visit laboratory
      monitoring improved the LDL testing interval but not LDL or HbA1c control, and it
      did not alter safety monitoring. Adoption of innovative tools to support
      physicians in non-visit-based chronic disease management may be limited by
      current visit-based financial and productivity incentives.

PMID- 25560320
TI  - Functional crosstalk between cardiac fibroblasts and adult cardiomyocytes by
      soluble mediators.
AB  - AIMS: Crosstalk between cardiomyocytes and fibroblasts in physiological
      conditions and during disease remains poorly defined. Previous studies have shown
      that fibroblasts and myocytes interact via paracrine communication, but several
      experimental confounding factors, including the use of immature myocytes and the
      induction of alpha-smooth muscle actin (alpha-SMA) expression in fibroblasts by
      prolonged culture, have hindered our understanding of this phenomenon. We
      hypothesize that fibroblasts and myofibroblasts differentially affect
      cardiomyocytes viability, volume, and Ca(2+) handling via soluble mediators. More
      specifically here: (i) we compare the effects of freshly isolated fibroblasts and
      cultured fibroblasts from normal rat hearts on adult cardiomyocytes; (ii) we
      compare the effects of (freshly isolated) normal fibroblasts and myofibroblasts
      from pressure-overloaded hearts; and (iii) we study the contribution of TGF-beta
      and the importance of the crosstalk between the two cell types. METHODS AND
      RESULTS: We used co-culture methods and conditioned medium to investigate
      paracrine interaction between fibroblasts and cardiomyocytes. All fibroblast
      types reduce cardiomyocyte viability and increase cardiomyocyte volume but alpha
      SMA-negative fibroblasts increase cardiomyocyte Ca(2+) transient amplitude,
      whereas cultured fibroblasts and myofibroblasts from pressure-overloaded hearts
      decrease Ca(2+) transient amplitude. In turn, cardiomyocytes release soluble
      mediators that affect fibroblast proliferation. Using SB431542 to block TGF-beta
      type 1 receptors, we determined that TGF-beta directly causes cardiomyocyte
      hypertrophy and participates in bi-directional regulatory signalling between
      fibroblasts and cardiomyocytes. CONCLUSIONS: Fibroblasts have different roles
      during physiology and disease in regulating myocardial function via soluble
      mediators. A crosstalk between fibroblasts and cardiomyocytes, controlled by TGF
      beta, is crucial in this interaction.

PMID- 25560321
TI  - Extracardiac control of embryonic cardiomyocyte proliferation and ventricular
      wall expansion.
AB  - AIMS: The strategies that control formation of the ventricular wall during heart
      development are not well understood. In previous studies, we documented IGF2 as a
      major mitogenic signal that controls ventricular cardiomyocyte proliferation and
      chamber wall expansion. Our objective in this study was to define the tissue
      source of IGF2 in heart development and the upstream pathways that control its
      expression. METHODS AND RESULTS: Using a number of mouse genetic tools, we
      confirm that the critical source of IGF2 is the epicardium. We find that
      epicardial Igf2 expression is controlled in a biphasic manner, first induced by
      erythropoietin and then regulated by oxygen and glucose with onset of placental
      function. Both processes are independently controlled by retinoic acid
      signalling. CONCLUSIONS: Our results demonstrate that ventricular wall
      cardiomyocyte proliferation is subdivided into distinct regulatory phases. Each
      involves instructive cues that originate outside the heart and thereby act on the
      epicardium in an endocrine manner, a mode of regulation that is mostly unknown in
      embryogenesis.

PMID- 25560322
TI  - Helicobacter pylori infection is associated with worse severity of Parkinson's
      disease.
AB  - BACKGROUND: Some studies have suggested that chronic Helicobacter pylori (HP)
      infection can aggravate the neurodegenerative process in Parkinson's disease
      (PD), and targeted intervention could potentially modify the course of this
      disabling disease. We aimed to study the impact of HP infection on motor
      function, gastrointestinal symptoms, and quality of life in a large cohort of PD
      patients. METHODS: 102 consecutive PD patients underwent (13)C urea breath
      testing and blinded evaluations consisting of the Unified Parkinson's Disease
      Rating Scale (UPDRS) including "On"-medication motor examination (Part III),
      objective and quantitative measures of bradykinesia (Purdue Pegboard and timed
      gait), Leeds Dyspepsia Questionnaire, and PDQ-39 (a health-related quality of
      life questionnaire). RESULTS: 32.4% of PD patients were HP-positive. HP-positive
      patients were older (68.4 +/- 7.3 vs. 63.8 +/- 8.6 years, P = 0.009) and had
      worse motor function (UPDRS Part III 34.0 +/- 13.0 vs. 27.3 +/- 10.0, P = 0.04;
      Pegboard 6.4 +/- 3.3 vs. 8.0 +/- 2.7 pins, P = 0.04; and timed gait 25.1 +/- 25.4
      vs. 15.5 +/- 7.6 s, P = 0.08). In the multivariate analysis, HP status
      demonstrated significant main effects on UPDRS Part III and timed gait. The
      association between HP status and these motor outcomes varied according to age.
      Gastrointestinal symptoms and PDQ-39 Summary Index scores did not differ between
      the two groups. CONCLUSIONS: This is the largest cross-sectional study to
      demonstrate an association between HP positivity and worse PD motor severity.

PMID- 25560323
TI  - Persistent parvovirus B19 viremia with chronic arthralgia treated with ascorbic
      acid: a case report.
AB  - INTRODUCTION: According to some studies, ascorbic acid possesses antiviral
      properties. These studies were mainly focused on the common cold, with very few
      focusing on other viral infections. CASE PRESENTATION: We report the case of a 54
      year-old Caucasian woman with chronic arthralgia due to persistent parvovirus B19
      viremia. High doses of ascorbic acid treatment were initiated due to the failure
      of conventional analgesic therapy. Clinical benefit was observed with a
      simultaneous loss of biological parvovirus B19 viremia. CONCLUSIONS: This
      observation shows a potential benefit of the use of ascorbic acid against
      parvovirus B19 infections, even if this case is not sufficient to draw any
      definite conclusions.

PMID- 25560324
TI  - The Scientific Revolution--The Kidney and Nephrology in and about the Seventeenth
      Century (Part 1).
AB  - In the history of the evolution of the medical sciences, it is in the 17th
      century that the conscious, deliberate, and systematic study of the workings of
      the human body began. It was a product of the radical changing attitudes of this
      insurgent century when mathematical reasoning and mechanistic philosophy replaced
      the teleological outlook of earlier times. It was then that meticulous
      observation, reproducible quantification, experimental validation, and
      mathematical exactitude in the quest for truths launched the Scientific
      Revolution. The effect on medicine was a transformative change from a descriptive
      to an explanatory body of knowledge during the course of which rigorous
      anatomical dissections were used for the mechanical explanation of organ
      function, when morbid changes observed at postmortem began to be related to
      clinical features of disease, and when the secretive analytical methods of
      alchemy began to be refined for the study of chemical changes in living matter.
      Essentially what began with meticulous observations of anatomical features begat
      physiology and laid the foundations of pathology and chemistry. As a result,
      studies of organ structure, function, and changes in disease in general, and of
      the kidney in particular, were clarified and progressed at a rate never achieved
      theretofore. 

PMID- 25560325
TI  - Changes in the characteristics of facial fractures in children and adolescents in
      Portugal 1993-2012.
AB  - We investigated the changes in the characteristics of facial fractures in
      children and adolescents during a 20-year period in Portugal to try to find out
      how to prevent such fractures in future. We reviewed the clinical records of
      patients aged 0-18 years old who had facial fractures treated at the Department
      of Plastic Surgery, Sao Joao Hospital, Porto, during the 20-year period 1993
      2012. The patients were divided into two 10-year periods: January 1993 to
      December 2002, and January 2003 to December 2012, and these were compared and
      analysed. A total of 1416 patients with 2071 fractures were diagnosed. There was
      a significant reduction (p<0.001) in the number of patients treated during the
      two decades. In both groups the number of patients increased with increasing age
      (p<0.001), and there was a male preponderance in all age groups. Motor vehicle
      collisions were the main cause of the fractures, and the mandible was the most
      common site (49.7%). Other injuries were recorded in 1015 patients (71.7%), and
      the head and neck was the most common site in both decades. Facial fractures in
      children are usually associated with severe trauma, and their characteristics can
      be influenced by social and economic factors. Although the number of children
      injured has decreased significantly during the last decade, facial fractures
      remain common in Portugal. 

PMID- 25560327
TI  - Quantitative Assessment of Myocardial Blood Flow with SPECT.
AB  - The quantitative assessment of myocardial blood flow (MBF) and coronary flow
      reserve (CFR) may be useful for the functional evaluation of coronary artery
      disease, allowing judgment of its severity, tracking of disease progression, and
      evaluation of the anti-ischemic efficacy of therapeutic strategies. Quantitative
      estimates of myocardial perfusion and CFR can be derived from single-photon
      emission computed tomography (SPECT) myocardial perfusion images by use of
      equipment, tracers, and techniques that are available in most nuclear cardiology
      laboratories. However, this method underestimates CFR, particularly at high flow
      rates. The recent introduction of cardiac-dedicated gamma cameras with solid
      state detectors provides very fast perfusion imaging with improved resolution,
      allowing fast acquisition of serial dynamic images during the first pass of a
      flow agent. This new technology holds great promise for MBF and CFR
      quantification with dynamic SPECT. Future studies will clarify the effectiveness
      of dynamic SPECT flow imaging. 

PMID- 25560326
TI  - Sclerosis in bisphosphonate-related osteonecrosis of the jaws and its correlation
      with the clinical stages: study of 43 cases.
AB  - We analysed the degree of sclerosis in the different stages of bisphosphonate
      related osteonecrosis of the jaws (BRONJ) and studied the relation between the
      grade of sclerosis, the clinical symptoms, and the depth of lucency. We compared
      43 patients with mandibular BRONJ with a control group of 40 cases with no bony
      lesions. The presence of sclerotic bone, cortical irregularities, radiolucency,
      fragmentation or sequestration, periostitis, and narrowing of the mandibular
      canal were studied from computed tomographic (CT) scans using the program ImageJ
      1.47v (National Institute of Health, Bethesda, USA) to measure the radiolucency,
      width of the cortices, and degree of sclerosis. Patients with BRONJ had more
      severe sclerosis than controls (p<0.01). There was also a significant difference
      among the different stages of BRONJ, with the highest values found in stage III
      (p=0.02). The degree of sclerosis differed according to sex, type of
      bisphosphonate, and the clinical characteristics such as pain, or suppuration,
      but not significantly so (p>0.05). We conclude that the degree of sclerosis
      increases with the clinical stage of BRONJ, and is correlated with the depth of
      lucency.

PMID- 25560328
TI  - Nature of job and psychiatric problems: the experiences of industrial workers.
AB  - AIM: The present study aimed to examine the effect of nature of job (High
      risk/low risk) on psychiatric problems of 200 workers of Tata Motors Ltd. in
      Jamshedpur. The workers/participants were divided on the basis of the nature of
      their job (high/low risk) and their salary (high/low paid) resulting in four sub
      groups with 50 participants respectively s. METHODS: The Middlesex Hospital
      Questionnaire (M.H.Q) constructed by Crown and Crisp (1966) and adapted in Hindi
      by Srivastava and Bhat in 1974 was administered on the participants. RESULTS:
      Results clearly indicated that nature of job (high and low risk) played a
      significant role in creating psychiatric problems in workers. Workers doing high
      risk jobs showed a greater amount of psychiatric problems compared to workers
      doing low risk jobs in both high paid and low paid categories. Psychiatric
      problems included free-floating anxiety, obsessional traits and symptoms, phobic
      anxiety, somatic concomitants of anxiety, neurotic depression, and hysterical
      personality traits were seen more in high risk job workers. CONCLUSIONS: High
      risk job workers had significantly higher psychiatric problems compared to low
      risk job workers.

PMID- 25560329
TI  - Parents' participation in the sexuality education of their children in rural
      Namibia: a situational analysis.
AB  - Talking about sexuality has never been easy in most Namibians cultures and it
      seems that most parents feel uncomfortable and embarrassed to talk openly with
      their children about sexuality. They do not participate in the sexuality
      education of their children, because they believe they are unable to provide
      quality and adequate sexuality information due to their lack of knowledge about
      human sexuality or their perceived inability to explain what they do know. The
      ultimate purpose of this study was to develop, describe, implement and evaluate
      an educational programme to empower rural parents to participate in the sexuality
      education of their children. The study was designed to be qualitative,
      explorative, descriptive and contextual in nature. It was performed in three
      phases. Phase 1 consisted of a situational analysis to explore and describe how
      parents provide sexuality education. Phase 2 consisted of the development of a
      conceptual framework that facilitated the development of an educational
      programme. In phase 3 the programme was implemented and evaluated,
      recommendations were made and conclusions drawn. The main findings revealed two
      themes: factors influencing parental participation in their children's sexuality
      education, and the need for parental participation in their children's sexuality
      education. This article is part of series of three article stems from a study on
      the topic of sexuality education empowerment programme of rural parents in
      Namibia. The three articles have the following titles: one: parent's
      participation in sexuality education of their children: a situational analysis;
      two: conceptual framework developments that facilitate the development of an
      educational programme and three: programme implementation and evaluation. This
      article dealt with parent's participation in sexuality education of their
      children: a situational analysis. 

PMID- 25560330
TI  - The effect of 8 weeks aerobic exercise on insulin resistance in type 2 diabetes:
      a randomized clinical trial.
AB  - Diabetes complications are the main reasons behind morbidity and mortality
      preventable by healthy diet and physical activity. There are few studies about
      the effect of aerobic exercises on insulin resistance in human. Also various
      training protocols are associated with different results. Since approaches to
      decrease insulin resistance may be followed by more effectiveness treatment, this
      study assessed the effect of aerobic exercise on insulin resistance in type 2
      diabetes mellitus. In this randomized clinical trial, 53 type 2 diabetic women
      were randomly divided into two groups as exercise (n=27) and control (n=26).The
      exercise protocol included warm-up by stretching and flexibility exercises for 10
      m, followed by walking for 30 m with maximum intensity 60% increase in heart rate
      and then stretching in the seated position for 10 m, 3 times a week for 8 weeks.
      Resistance to insulin was assessed using Homeostasis Model Assessment of Insulin
      Resistance (HOMA-IR). Significant differences have been observed in insulin
      resistance, fasting glucose and plasma insulin between the groups after 8 weeks.
      There were significant differences in waist and hip circumference, BMI, plasma
      insulin and insulin resistance within the groups over time. In addition, the
      changes in waist and hip circumference, FBS, plasma insulin and insulin
      resistance had significant interaction with the time between the groups. The
      current exercise protocol has been effective in lowering plasma glucose (p =
      0.05), insulin levels (p = 0.000) and insulin resistance (p = 0.02). It seems
      that aerobic exercises training promote the effectiveness of medical treatment in
      type 2 diabetes mellitus.

PMID- 25560331
TI  - Vitamin D and its relationship with breast cancer: an evidence based practice
      paper.
AB  - BACKGROUND: In oncology research fields, vitamin D has emerged as the most
      fruitful issue. The previous decade witnessed intensive efforts in connecting
      vitamin D with risk reduction and progression of various epithelial cancers,
      especially, breast cancer. PURPOSE: To evaluate the relationship between vitamin
      D levels and breast cancer. METHOD: A comprehensive search of several electronic
      databases was conducted in Pub Med, MEDLINE, CINAHL, in addition to, web search
      engine "Google" for abstracts, in order to determine the relationship between
      vitamin D and breast cancer. RESULTS: It was found that an increased serum level
      of vitamin D is associated with decreased risk of breast cancer. CONCLUSION: It
      was concluded that vitamin D plays a significant role in protection of breast
      cancer.

PMID- 25560332
TI  - Proactive risk assessment of blood transfusion process, in pediatric emergency,
      using the Health Care Failure Mode and Effects Analysis (HFMEA).
AB  - INTRODUCTION: Pediatric emergency has been considered as a high risk area, and
      blood transfusion is known as a unique clinical measure, therefore this study was
      conducted with the purpose of assessing the proactive risk assessment of blood
      transfusion process in Pediatric Emergency of Qaem education- treatment center in
      Mashhad, by the Healthcare Failure Mode and Effects Analysis (HFMEA) methodology.
      METHODOLOGY: This cross-sectional study analyzed the failure mode and effects of
      blood transfusion process by a mixture of quantitative-qualitative method. The
      proactive HFMEA was used to identify and analyze the potential failures of the
      process. The information of the items in HFMEA forms was collected after
      obtaining a consensus of experts' panel views via the interview and focus group
      discussion sessions. RESULTS: The Number of 77 failure modes were identified for
      24 sub-processes enlisted in 8 processes of blood transfusion. Totally 13 failure
      modes were identified as non-acceptable risk (a hazard score above 8) in the
      blood transfusion process and were transferred to the decision tree. Root causes
      of high risk modes were discussed in cause-effect meetings and were classified
      based on the UK national health system (NHS) approved classifications model.
      Action types were classified in the form of acceptance (11.6%), control (74.2%)
      and elimination (14.2%). Recommendations were placed in 7 categories using TRIZ
      ("Theory of Inventive Problem Solving.") CONCLUSION: The re-engineering process
      for the required changes, standardizing and updating the blood transfusion
      procedure, root cause analysis of blood transfusion catastrophic events, patient
      identification bracelet, training classes and educational pamphlets for raising
      awareness of personnel, and monthly gathering of transfusion medicine committee
      have all been considered as executive strategies in work agenda in pediatric
      emergency.

PMID- 25560333
TI  - The perception of biological experience in patients with major Thalassemia: a
      qualitative research.
AB  - BACKGROUND: Thalassemia Major Disease is not only assumed as a health disorder,
      but also a social- economic problem in many countries. The costs of transport and
      preparation of drugs is considered as the greatest problems for more than 63.8%
      of the patients' families. This study was conducted by aiming at describing
      biological experience among parents of patients with Thalassemia Major. METHOD:
      The current qualitative investigation was carried out on 32 parents of patients
      with Thalassemia Major and by means of unstructured interview in- depth through
      snowball sampling technique in 2013. The data were analyzed by conventional
      content analytical method. FINDINGS: The perception of biological experience of
      parents of patients with Thalassemia Major were classified based on participants'
      experiences into three main themes including psychological experiences, physical
      experiences, and social experiences. 1) Psychological (mental) experiences
      comprise of two subclasses of the reduced self-confidence, deficient emotions and
      negative emotions; 2) Physical experiences consist of three subclasses of
      sleeping disorders, pains in various parts of body, and limited physical
      activity; and 3) Social experiences includes 3 subcategories of interpersonal
      relations, reduced income, job, and limitation in doing tasks. 4) Treatment
      experiences comprise of five sub-themes including 1- Shortage of drugs, blood,
      and filter etc; 2- Less experienced personnel; 3- Lack of training the patients'
      parents by personnel in thalassemia ward; 4- Lack of visiting patients by
      physician in thalassemia ward; and 5- Inappropriate behavior of personnel toward
      patients and their parents. CONCLUSION: Thalassemia Major has affected negatively
      on several fields of health for these patients and their parents including
      physical, mental, economic, and social areas. Reducing these problems requires
      constant interventions and surveying health and medical status of these patients.

PMID- 25560334
TI  - A review article of the reduce errors in medical laboratories.
AB  - The current article examines the modern practices of reducing errors in medical
      laboratories. The paper sought to examine the methods that different countries
      are applying to reduce errors in medical laboratories. In addition, the paper
      examines the relationship between inadequate training of laboratory personnel and
      error causation in medical laboratories. A total of 17 research articles have
      been reviewed. The paper has done a comparison of pathology laboratory practices
      in the US, Canada, the UK and Australia, regarding laboratory staff skills and
      error reduction. The paper finds out that; although some of the developed
      countries have employed advanced technology to reduce errors, there is still a
      great need to use sophisticated medical equipment to reduce errors. In addition,
      the levels of training for the medical technicians are still low. They are not
      equipped enough to reduce the errors to the required levels. The article
      recommends application of advanced technology in the reduction of errors, and
      training of technicians on the best practices to reduce errors. 

PMID- 25560335
TI  - Challenges of the health research system in a medical research institute in Iran:
      a qualitative content analysis.
AB  - BACKGROUND & AIM: Medical research institute is the main basis for knowledge
      production through conducting research, and paying attention to the research is
      one of the most important things in the scientific communities. At present, there
      is a large gap between knowledge production in Iran compared to that in other
      countries. This study aimed to identify the challenge of research system in a
      research institute of medical sciences in Iran. MATERIALS & METHODS: This was a
      descriptive and qualitative study conducted in the first 6 months of 2013. A
      qualitative content analysis was conducted on 16 heads of research centers in a
      research institute of medical sciences. The required data were gathered using
      semi-structured interviews. The collected data were analyzed using MAXQDA 10.0
      software. RESULTS: Six themes identified as challenges of research system. The
      themes included barriers related to the design and development, and approval of
      research projects, the implementation of research projects, the administrative
      and managerial issues in the field of research, the personal problems, publishing
      articles, and guidelines and recommendations. CONCLUSION: Based on the results of
      the present study, the following suggestions can be offered: pushing the research
      towards solving the problems of society, employing the strong executive and
      scientific research directors in the field of research, providing training
      courses for researchers on how to write proposals, implementing administrative
      reforms in the Deputy of Research and Technology, accelerating the approval of
      the projects through automating the administrative and peer-reviewing processes.

PMID- 25560336
TI  - The structure of clinical consultation: a case of non-native speakers of English
      as participants.
AB  - BACKGROUND: In many parts of the world, patients may find it difficult to visit
      doctors who share the same language and culture due to the intermingling of
      people and international recruitment of doctors among many other reasons. In
      these multilingual multicultural settings (MMSs), doctor-patient interactions
      face new communication challenges. This study aims to identify the structure of
      clinical consultation and its phases in an MMS where both doctors and patients
      are non-native speakers (NNSs) of English. METHOD: This study takes on a
      discourse analytic approach to examine the structure of clinical consultation as
      an activity type. 25 clinical consultation sessions between non-native speakers
      of English in a public healthcare centre in Malaysia were audio-recorded.
      FINDINGS & DISCUSSION: The results show that there are some deviations from the
      mainstream structure of clinical consultations although, in general, the pattern
      is compatible with previous studies. Deviations are particularly marked in the
      opening and closing phases of consultation. CONCLUSION: In almost all
      interactions, there is a straightforward manner of beginning medical
      consultations. The absence of greetings may have naturally reduced the length of
      talk. Hence, by directly entering medical talks, the doctors voice their concern
      on the curing aspects of the consultation rather than its caring facets. The
      preference of curing priority to caring is more goal-oriented and in alignment
      with the consultation as an activity type.

PMID- 25560337
TI  - Implementation status of accrual accounting system in health sector.
AB  - INTRODUCTION: Management of financial resources in health systems is one of the
      major issues of concern for policy makers globally. As a sub-set of financial
      management, accounting system is of paramount importance. In this paper, which
      presents part of the results of a wider research project on transition process
      from a cash accounting system to an accrual accounting system, we look at the
      impact of components of change on implementation of the new system. Implementing
      changes is fraught with many obstacles and surveying these challenges will help
      policy makers to better overcome them. METHODS: The study applied a quantitative
      manner in 2012 at Kerman University of Medical Science in Iran. For the
      evaluation, a teacher made valid questionnaire with Likert scale was used
      (Cranach's alpha of 0.89) which included 7 change components in accounting
      system. The study population was 32 subordinate units of Kerman University of
      Medical Sciences and for data analysis, descriptive and inferential statistics
      and correlation coefficient in SPSS version 19 were used. RESULTS: Level of
      effect of all components on the implementation was average downward (5.06+/
      1.86), except for the component "management & leadership (3.46+/-2.25)"
      (undesirable from external evaluators' viewpoint) and "technology (6.61+/-1.92)
      and work processes (6.35+/-2.19)" (middle to high from internal evaluators'
      viewpoint). CONCLUSIONS: Results showed that the establishment of accrual
      accounting system faces infrastructural challenges, especially the components of
      leadership and management and followers. As such, developing effective measures
      to overcome implementation obstacles should target these components.

PMID- 25560338
TI  - An empirical study of the impact of service quality on patient satisfaction in
      private hospitals, Iran.
AB  - OBJECTIVE: Perceived service quality is the most important predictor of patient
      satisfaction. The purpose of this study was to investigate the impact of the
      service quality on the overall satisfaction of patients in private hospitals of
      Tehran, Iran. METHOD: This cross-sectional study was conducted in the year 2010.
      The study's sample consisted of 969 patients who were recruited from eight
      private general hospitals in Tehran, Iran using consecutive sampling. A
      questionnaire was used for data collection; contacting 21 items (17 items about
      service quality and 4 items about overall satisfaction) and its validity and
      reliability were confirmed. Data analysis was performed using t-test, ANOVA and
      multivariate regression. RESULT: this study found a strong relationship between
      service quality and patient satisfaction. About 45% of the variance in overall
      satisfaction was explained by four dimensions of perceived service quality. The
      cost of services, the quality of the process and the quality of interaction had
      the greatest effects on the overall satisfaction of patients, but not found a
      significant effect on the quality of the physical environment on patient
      satisfaction. CONCLUSIONS: Constructs related to costs, delivery of service and
      interpersonal aspect of care had the most positive impact on overall satisfaction
      of patients. Managers and owners of private hospitals should set reasonable
      prices compared to the quality of service. In terms of process quality, waiting
      time for visits, admissions, and surgeries must be declined and services provided
      at the fastest possible time. It should be emphasized to strengthen of
      interpersonal aspects of care and communication skills of care providers.

PMID- 25560339
TI  - Effectiveness of diabetes self-management education on quality of life in
      diabetic elderly females.
AB  - INTRODUCTION: Diabetes is a chronic illness that requires continuing medical care
      and patient self-management education to reduce the risk of long-term and acute
      complications. The aim of the present study was to determine the effectiveness of
      diabetes self-management education on quality of life in elderly females with
      diabetic mellitus (type 2) in Shiraz, Iran, 2013. METHOD: The study was conducted
      from January to April 2014 at the Jahandidegan center, a day center affiliated to
      Shiraz welfare organization. The instrument used for the study was the Quality of
      life Questionnaire (WHO QOL-BREF) SF26. After an explanation of the aim of the
      study by the researcher, 90 participants with all the required criteria and G.H.Q
      score ? 23 were selected as the study sample for the intervention. Participants
      divided into experimental and control groups, and completed WHO QOL-BREF before
      the intervention, 2 and 3 months after the last session of education. RESULT: It
      is shown that 2 and 3 months after the intervention, QOL scores had a significant
      difference between the two groups. In other words, the training sessions improved
      the score of QOL in the intervention group (P < 0.001) versus control group (P =
      0.5). CONCLUSION: The Behavioral Intervention Program significantly improved the
      quality of life outcomes of the diabetic elderly females. Thus, it is concluded
      that the diabetic individuals can be significantly improved following instruction
      by health care providers.

PMID- 25560340
TI  - Knowledge about HIV/AIDS among high school students in Erbil city/Iraq.
AB  - BACKGROUND & OBJECTIVES: HIV/AIDS is as a major public health problem which leads
      to serious challenges to humankind globally. The aim of this study was to assess
      the knowledge about HIV/AIDS among high school students in Erbil city and to
      investigate the association between high school students' socio-demographic
      characteristics and their level of knowledge about HIV/AIDS. METHODS: This
      descriptive cross-sectional study was carried out in three high schools in Erbil
      city from February to April 2014. A sample of 437 students was included in the
      study from fourth, fifth and sixth stages. A multistage cluster sampling method
      was used to select the students. Data analysis included descriptive statistics
      and chi-square association test for categorical variables. RESULTS: The age range
      of the students was between 14 and 21 years with mean +/- standard deviation of
      16.0 +/- 0. 927 years. All the students had heard about AIDS where around two
      thirds of students had heard from mass media like TV/Radio. Around 45% of
      students had good knowledge scores about HIV/AIDS, and 43.7% had acceptable
      knowledge scores, while only 11.2% had poor knowledge scores. There was a
      statistically significant association between high knowledge score about HIV/AIDS
      with older age, male gender, and typical school type (P < 0.001). High socio
      economic status of students was significantly associated with high score of
      knowledge about HIV/AIDS (P = 0.005). CONCLUSION: The overall rate of knowledge
      (acceptable and good) about HIV/AIDS among high school students was high. Socio
      demographic characteristics of students have an effect on their knowledge about
      HIV/AIDS.

PMID- 25560341
TI  - Study of survival rate after cardiopulmonary resuscitation (CPR) in hospitals of
      Kermanshah in 2013.
AB  - BACKGROUND: After CPR, the follow-up of survival rate and caused complications
      are the most important practices of the medical group. This study was performed
      aimed at determining the follow-up results after CPR in patients of university
      hospitals in Kermanshah in 2014. METHODS: In this prospective study, 320 samples
      were examined. A purposive sampling method was used, and data was collected using
      a researcher-made information form with content and face validity and reliability
      of r= 0.79. Data was analyzed with STATA9 software and statistical tests,
      including calculation of the success rate, relative risk (RR), chi-square and
      Fisher at significance level of P < 0.05. RESULTS: The initial success rate of
      cardiopulmonary resuscitation was equal to 15.3%, while the ultimate success rate
      (discharged alive from the hospital) was as 10.6%. The six-month success rate
      after resuscitation was 8.78% than those who were discharged alive. There were no
      significant statistical differences between different age groups regarding the
      initial success rate of resuscitation (P = 0.14), and the initial resuscitation
      success rate was higher in patients in morning shift (P = 0.02). CONCLUSION: By
      the results of study, it is recommended to increase the medical - nursing
      knowledge and techniques for personnel in the evening and night shifts. Also, an
      appropriate dissemination of health care staff in working shifts should be done
      to increase the success rate of CPR procedure.

PMID- 25560342
TI  - Low dose furazolidone for eradication of H- pylori instead of clarithromycin: a
      clinical trial.
AB  - BACKGROUND: Helicobacter pylori infection is a common chronic human bacterial
      infection. Triple- therapy regimen containing a proton pump inhibitor,
      clarithromycin, and either amoxicillin or metronidazole is commonly used as first
      line treatment for its eradication. However, it may not provide the acceptable
      eradication rate. The present study was designed to evaluated efficacy of low
      dose furazolidone with amoxicillin and omeprazole for eradication of H- pylori.
      MATERIALS & METHODS: One hundred twenty patients with non- ulcer dyspepsia or
      peptic ulcer confirmed by upper GI endoscopy, plus H- pylori infection confirmed
      by rapid urease test were included in the study. They were randomly divided into
      two groups, and then received clarithromycin, amoxicillin, and omeprazole, or
      furazolidone (100 mg PO bid), amoxicillin, and omeprazole. They were evaluated
      using urea breath test at the end of the study. FINDINGS: The eradication rates
      were 57.6% and 78.8% in clarithromycin and furazolidone groups, respectively.
      Their difference was statistically significant (P value 0.013). No side effect
      was seen in the furazolidone group. CONCLUSION: Low dose furazolidone rather than
      clarithromycin can be used as low- cost and effective drug for eradication of H-
      pylori, in combination with amoxicillin and omeprazole.

PMID- 25560343
TI  - Powerful leverages and counter-currents in the unborn child spiritual care: a
      qualitative study.
AB  - In different cultures, pregnancy, birth and motherhood are perceived as spiritual
      events through their miraculous processes and create an ideal context for
      spiritual enrichment. However, studies on spirituality and birth are at very
      early stages. The purpose of this study was to understand the facilitators and
      barriers of the unborn child spiritual care in Iranian women. Twenty-two mothers
      with live pregnancy experience who were willing and able to share their life
      stories were selected purposefully in Tehran (Iran) from May 2012 to April 2013.
      Qualitative content analysis was used to analyze 27 interviews. Active and
      passive acquisition of information, inner inspirational messages, receiving
      effective support from the people around as well as modeling of self and
      significant others created "powerful leverages" to accelerate mother for caring
      her unborn child. "Counter-currents" in the form of unsuitable physical
      conditions during pregnancy, poor economic and social conditions, unsuitable
      psychological and cognitive conditions and finally understanding unsuitable
      ideological conditions of the self and care giver were identified as barriers.
      Iranian cultural and religious perspective on the unborn child physical and
      mental influence from mother has an important role in mother's self-care
      behaviors during pregnancy. It seems that using interdisciplinary professionals'
      skills based on understanding facilitators and barriers of mother care of the
      unborn child can lead to providing comprehensive prenatal care according to
      mothers' cultural, religious and social context. 

PMID- 25560344
TI  - Prevalence and predictors of clinically significant depressive symptoms among
      Chinese and Malawian children: a cross-cultural comparative cross-sectional
      study.
AB  - BACKGROUND: Multicultural comparative studies have recently increased scientific
      knowledge base regarding the mental health of diverse populations. This cross
      cultural study was cross-sectionally designed to assess differences in the
      prevalence and predictors of clinically significant depressive symptoms between
      Chinese and Malawian children. METHODS: A total of 478 children (237 Chinese and
      241 Malawians) were randomly recruited in the study. The participants completed a
      Children Depression Inventory in the dimensions of Negative Mood, Interpersonal
      Problems, Ineffectiveness, Anhedonia, and Negative Self- Esteem. They further
      provided demographic and family structure information. Data were analyzed by
      Student's t-test, Chi-square test, and logistic regression. RESULTS: The
      prevalence of clinically significant depressive symptoms was 16% and 12.4% for
      Chinese and Malawian study participants, respectively. Multivariate logistic
      regression analysis showed that fighting among siblings (adjusted odds ratio
      [aOR] = 4.1, 95% CI, 3.5-5.9), fighting among children and parents (aOR = 7.7,
      95% CI, 4.6-9.8) and living with father only (aOR = 4.1, 95% CI, 3.4-6.7) were
      significant predictors of clinically significant depressive symptoms among
      Chinese study participants. On the other hand, clinically significant depressive
      symptoms were predicted by employment status of a mom only among Malawian study
      participants (aOR = 3.0, 95% CI, 2.3-5.9). CONCLUSIONS: We conclude that diverse
      cultures affect children's mental health differently and this cluster of children
      has a noticeable amount of depressive symptoms that in the least requires further
      diagnosis and preventive measures.

PMID- 25560345
TI  - Nursing process in post tonsillectomy pain diagnosis: a systematic review.
AB  - OBJECTIVE: Tonsillectomy is the most common surgery in the field of ENT. Pain is
      the most common post tonsillectomy complaint. Considering the importance of
      nursing cares in relieving post-surgery pain in general and post-tonsillectomy
      pain in particular, this study is conducted with the aim of presenting nursing
      process in post tonsillectomy pain diagnosis for decreasing loss of appropriate
      opportunities in nursing cares and achieving appropriate results in taking care
      of the patients. METHODS: This study is a targeted systematic review focusing on
      "effective nursing measures in relieving children's post tonsillectomy pain". The
      main stages of searching strategy included searching in electronic sources of
      Latin databases; Pub Med, Science Direct, and EMBASE and Persian databases; SID,
      Iran medex, ISC to find published articles from 2009 to 2014. In the end, final
      synthesis was done on eight articles in English. FINDINGS: Effective nursing
      measurements for relieving post tonsillectomy pain include: decreasing children's
      anxiety through children and their families' psychological preparation by nurses
      and other caregivers, using cold compress to reduce neck and jaw pain, presenting
      distraction techniques, offering fluids and cold foods immediately in the period
      after surgery, creating a comfortable environment for the children, avoiding too
      much of talking and adequate sleep. CONCLUSION: It is recommended to the nursing
      managers and nurses to perform cares achieved from this systematic review to
      achieve appropriate results in relieving post tonsillectomy pain.

PMID- 25560346
TI  - Cost-effectiveness analysis of trastuzumab in the adjuvant treatment for early
      breast cancer.
AB  - BACKGROUND: Evidence from randomized controlled trials (RCTs) has shown a
      significant survival advantage of trastuzumab. Although extant work in developed
      countries examined economic evaluation of trastuzumab in adjuvant treatment for
      early breast cancer based on the 1-year treatment, there is uncertainty about
      cost-effectiveness of trastuzumab in the Adjuvant Treatment of early breast
      cancer in developing countries. This study aimed to estimate cost-effectiveness
      of adjuvant trastuzumab therapy compared to AC-T regimen in early breast cancer
      in Iran. METHODS: A cost-effectiveness analysis was performed using a Markov
      model to estimate outcomes and costs over a 20-year time period using a cohort of
      women with HER2 positive early breast cancer, treated with or without 12 months
      trastuzumab adjuvant chemotherapy. Transition probabilities were derived mainly
      from the BCIRG006 trial. Costs were estimated from the perspective of the Iranian
      health care system. Both costs and outcomes were discounted by 3%. One-way
      sensitivity analysis was undertaken to assess the associated uncertainties in the
      expected output measures. RESULTS: On the basis of BCIRG006 trial, our model
      showed that adjuvant trastuzumab treatment in early breast cancer, yield 0.87
      quality-adjusted life-years (QALY) compared with AC-T regimen. Adjuvant
      trastuzumab treatment yielded an incremental cost-effectiveness ratio (ICER) of
      US$ 51302 per QALY. CONCLUSION: By using threshold of 3 times GDP per capita, as
      per World Health Organization (WHO) recommendation, 12 months trastuzumab
      adjuvant chemotherapy is not a cost-effective therapy for patients with HER2
      positive breast cancer in Iran.

PMID- 25560347
TI  - Using data mining to detect health care fraud and abuse: a review of literature.
AB  - Inappropriate payments by insurance organizations or third party payers occur
      because of errors, abuse and fraud. The scale of this problem is large enough to
      make it a priority issue for health systems. Traditional methods of detecting
      health care fraud and abuse are time-consuming and inefficient. Combining
      automated methods and statistical knowledge lead to the emergence of a new
      interdisciplinary branch of science that is named Knowledge Discovery from
      Databases (KDD). Data mining is a core of the KDD process. Data mining can help
      third-party payers such as health insurance organizations to extract useful
      information from thousands of claims and identify a smaller subset of the claims
      or claimants for further assessment. We reviewed studies that performed data
      mining techniques for detecting health care fraud and abuse, using supervised and
      unsupervised data mining approaches. Most available studies have focused on
      algorithmic data mining without an emphasis on or application to fraud detection
      efforts in the context of health service provision or health insurance policy.
      More studies are needed to connect sound and evidence-based diagnosis and
      treatment approaches toward fraudulent or abusive behaviors. Ultimately, based on
      available studies, we recommend seven general steps to data mining of health care
      claims. 

PMID- 25560348
TI  - Health outcomes for older Hispanics with HIV in New York City using the Oaxaca
      Decomposition Approach.
AB  - Although HIV and aging are two well-established medical and economic domains,
      their intersection represents an emerging area of study. Older adults with HIV,
      who sill comprise 50% of the US HIV-infected population by 2015, are
      disadvantaged as evidenced by disproportionately poorer health outcomes. The
      Oaxaca Decomposition Approach (ODA) was used to analyze data from the Research on
      Older Adults with HIV (ROAH) Study of 1,000 older adults with HIV in New York
      City (NYC). This paper establishes the sources of health disparities for
      Hispanics with HIV compared to a match group of Non-Hispanics with HIV. The ODA
      analyses shows that Hispanics on average have higher levels of declining health
      and increased depression attributable to the discrimination factor. 

PMID- 25560349
TI  - Aloe vera gel and cesarean wound healing; a randomized controlled clinical trial.
AB  - BACKGROUND: Failure in complete healing of the wound is one of the probable
      complications of cesarean. The present study aimed to determine the effectiveness
      of dressing with aloe vera gel in healing of cesarean wound. METHODS: This
      prospective randomized double-blind clinical trial was conducted on 90 women who
      had undergone cesarean operation in Amir-al-Momenin hospital (Gerash, Iran). The
      participants were randomly divided into two groups each containing 45 patients.
      In one group, the wound was dressed with aloe vera gel, while simple dressing was
      used in the control group. Wound healing was assessed 24 hours and 8 days after
      the cesarean operation using REEDA scale. The data were analyzed through Chi
      square and t-test. RESULTS: The participants' mean age was 27.56+/-4.20 in the
      aloe vera group and 26.62+/-4.88 in the control group, but the difference was not
      statistically significant. However, a significant difference was found between
      the two groups concerning body mass index, heart rate, and systolic blood
      pressure (P<0.05). Also, a significant difference was observed between the two
      groups with respect to the wound healing score 24 hours after the operation
      (P=0.003). After 8 days, however, the difference in the wound healing score was
      not significant (P=0.283). Overall, 45 participants in the aloe vera group and 35
      ones in the control group had obtained a zero score 24 hours after the operation.
      These measures were respectively obtained as 42 and 41eight days after the
      operation. CONCLUSION: According to the findings of this study, the women are
      recommended to be informed regarding the positive effects of dressing with aloe
      vera gel.

PMID- 25560350
TI  - Do self-perceptions of emotional intelligence predict health-related quality of
      life? A case study in hospital managers in Greece.
AB  - The aim of this study was to examine HRQoL outcome and EI of managers of Health
      Organizations. We collected data from 120 general managers of Greek public
      hospitals who completed the Assessing Emotions Scale (AES) and the SF-36 Health
      Survey. The results showed that male managers generally exhibited better HRQoL
      and slightly worse EI than females, although differences were not significant
      throughout. The three EI factors of the AES addressing appraisal,
      optimism/regulation and utilization of emotions correlated from 0.18 to 0.39 with
      sub-dimensions of HRQoL mostly related to mental -rather than physical- aspects
      of health, and were also significant predictors of HRQoL. There was a noteworthy
      gender difference in the manner in which EI predicted HRQoL and this suggests
      more testing. Overall, this study might enrich the potential for EI studies in
      Greece as well as to contribute to the international literature. 

PMID- 25560351
TI  - Tumultuous atmosphere (physical, mental), the main barrier to emergency
      department inter-professional communication.
AB  - BACKGROUND: A highly important factor in enhancing quality of patient care and
      job satisfaction of health care staff is inter-professional communication. Due to
      the critical nature of the work environment, the large number of staff and units,
      and complexity of professional tasks and interventions, inter-professional
      communication in an emergency department is particularly and exceptionally
      important. Despite its importance, inter-professional communication in emergency
      department seems unfavorable. Thus, this study was designed to explain barriers
      to inter-professional communication in an emergency department. METHODOLOGY &
      METHODS: This was a qualitative study with content analysis approach, based on
      interviews conducted with 26 participants selected purposively, with diversity of
      occupation, position, age, gender, history, and place of work. Interviews were in
      depth and semi-structured, and data were analyzed using the inductive content
      analysis approach. RESULTS: In total, 251 initial codes were extracted from 30
      interviews (some of the participants re-interviewed) and in the reducing trend of
      final results, 5 categories were extracted including overcrowded emergency,
      stressful emergency environment, not discerning emergency conditions, ineffective
      management, and inefficient communication channels. Tumultuous atmosphere
      (physical, mental) was the common theme between categories, and was decided to be
      the main barrier to effective inter-professional communication. CONCLUSION:
      Tumultuous atmosphere (physical-mental) was found to be the most important
      barrier to inter-professional communication. This study provided a better
      understanding of these barriers in emergency department, often neglected in most
      studies. It is held that by reducing environmental turmoil (physical-mental),
      inter-professional communication can be improved, thereby improving patient care
      outcomes and personnel job satisfaction.

PMID- 25560352
TI  - Prolonged second stage of labor and levator ani muscle injuries.
AB  - OBJECTIVE: To determine the effect of pregnancy and vaginal delivery on the
      pelvic floor and levatorani morphology and function. METHODS: Design. Cross
      sectional study. Setting. Tertiary care teaching hospital. Population. 75
      primigravid women were recruited for assessment at 6 weeks postpartum compared
      with 25 nulliparous women. Hiatal morphology and levator ani muscle avulsion were
      assessed by 4-dimensional translabial ultrasound examination. The volume
      achievement obtained by ultrasound was performed in supine position with empty
      bladder at rest, on maximum Valsalva maneuver, and on maximum pelvic floor muscle
      contraction. Main Outcome Measures. Hiatal diameter and area were measured at the
      plane of minimal hiatal dimension as defined in the midsagittal plane and Levator
      avulsion was assessed. RESULTS: There were significant differences in hiatal area
      morphology at rest, on Valsalva maneuver and during contraction of muscles among
      the study groups, but there was no difference in pelvic diameter at rest, on
      Valsalva maneuver, and during contraction. There were 21 cases of puborectalis
      avulsion (42%) with no significant difference between non-progressive labor (8
      cases) and Normal Vaginal Delivery (NVD) (13 cases) groups. CONCLUSIONS: The
      results of the present study showed that non-progressive labor is the main risk
      factor for pelvic muscle injuries, indicating the necessity of a better
      management and timely cesareans in women with prolonged second stage of labor.

PMID- 25560353
TI  - Erectile dysfunction among male hypertensives in a tertiary health facility in
      South-West Nigeria.
AB  - INTRODUCTION: Erectile dysfunction (ED) has been associated with hypertension and
      some other chronic diseases. There are few studies on ED in Nigerian male
      hypertensives and ED appears to be under-reported. We sought to determine the
      prevalence of ED among hypertensive and normotensive men and to assess the
      association of demographics, hypertension, antihypertensive medications and other
      risk factors with erectile function. METHODS: A comparative cross sectional study
      was conducted among male adult hypertensive and normotensive patients attending
      the outpatient clinic of a tertiary hospital in South-West Nigeria. A systematic
      random sampling method was employed for the selection of respondents.
      Participants were interviewed using a semi-structured questionnaire to document
      socio-demographic data, medical history, social history and degree of ED.
      Demographic and anthropometric characteristics was obtained from all
      participants. The International Index of Sexual Health Inventory for men (SHIM)
      was used to determine the presence and severity of ED. Association between
      categorical independent variables and erectile function were tested using Chi
      square and the predictors of erectile dysfunction determined with binary logistic
      regression model at 5% level of significance. RESULTS: A total of 202 male
      patients completed the study (101 with established hypertension and 101
      normotensives who served as comparative group). The mean age of the respondents
      was 49.74 +/- 16.6 years. A total of 133 (65.8%) respondents had ED in varying
      severities while 34.2% had normal erectile function. Mild to moderate ED occurred
      in 29.7% while 36.1% had severe ED. On bivariate analysis, prevalence of ED was
      higher among hypertensives (75%) than normotensives (56.9%) and this was
      statistically significant, p = 0.007. On multivariate analysis, the only
      significant risk factor for ED was age. The elderly aged ? 65 years (OR: 2.9; 95%
      CI: 1.03-8.35; p = 0.04) and those aged 46-64 years (OR: 2.9; 95% CI: 1.38-6.53;
      p = 0.006) were 3 times each more likely to have erectile dysfunction compared
      with those aged ? 45 years. CONCLUSION: This study revealed that erectile
      dysfunction was prevalent in both hypertensive and normotensive population
      studied and that this was significantly worse with increasing age. A higher
      proportion of hypertensives compared to normotensives had erectile dysfunction.
      We recommend that all men presenting to a physician should have routine
      evaluation for ED so as to recognise it early and reduce its effects.

PMID- 25560354
TI  - Socio-economic status of patients with type 2 diabetes and hypertension attending
      the Ahmadu Bello University Teaching Hospital, Zaria, North-West Nigeria.
AB  - Hypertension (HTN) and Type 2 diabetes (T2D) are lifestyle interrelated diseases
      of global significance. Interestingly, the prevalence of these diseases in Africa
      and indeed Nigeria seems to be on the increase. This study, therefore,
      investigated the socioeconomic status (based on income, education and
      occupational activity) of 400 subjects (52% female and 48% male) aged 20 years
      and above who were sampled randomly among the newly diagnosed HTN and/or T2D
      cases at the Ahmadu Bello University Teaching Hospital, Zaria, North-West
      Nigeria. A semi-structured questionnaire was used to collect information from the
      subjects. From the result obtained, most of the respondents who live in towns or
      city suffer from either HTN or T2D while more town dwellers (28%) suffer from a
      combination of both diseases. It was also discovered that most respondents who
      suffer from HTN and from a combination of HTN and T2D belong to the old
      generation (60-79 years). There is higher prevalence rate of diabetes among the
      respondents who had no formal education or attended only basic Arabic schools.
      Most respondents who earn good income (NGN50,000-NGN100,000 and above NGN100,000)
      suffer HTN, T2D and a combination of both diseases. Those engaged in heavy
      occupational activities had the lowest prevalence of the disease compared with
      those of light or moderate occupational activities. These data will be found
      useful in planning intervention healthcare preventive programs especially on
      public enlightenment workshops and seminars to educate the populace on the
      importance of lifestyle modification, healthy diet and regular exercises. 

PMID- 25560355
TI  - Gender comparisons of physical fitness indexes in Inner Mongolia medical students
      in China.
AB  - INTRODUCTION: The aim of present study was to investigate gender differences in
      physical fitness indexes in regard to BMI (body mass index) levels among Inner
      Mongolia medical students in China. METHODS: Data on participant characteristics
      came from basic information contained in the school database. Physical fitness
      indexes including BMI, vital capacity index, sidestep test, and standing long
      jump, were conducted. RESULTS: Female students had a higher rate of normal weight
      than those of males. The obesity rate of males was 5 times higher compared to
      females. Compared with male students, female students had a higher pass rate in
      vital capacity index, sidestep and standing long jump. Females were higher 17%
      than males in the pass rate of the sidestep test. Males performed better than
      females in the standing long jump. In both the malnutrition and normal weight
      group, the pass rate of the 3 physical fitness indexes for both male and female
      students was higher than obese group. The not pass rate was higher than pass rate
      both male and female students in the vital capacity index in the obese group.
      DISCUSSION: Males had a poor physical fitness level compared with females. Male
      students may be more likely to spend more time using computers and it will cut
      down the time of participating in physical activities. So, in our university,
      more attention should pay on physical education, especially for males.

PMID- 25560356
TI  - Occupational health risks among trichloroethylene-exposed workers in a clock
      manufacturing factory.
AB  - Trichloroethylene (TCE) is an important volatile organic compound once widely
      used in industry throughout the world. Occupational exposure to TCE can cause a
      number of health hazards such as allergic reactions and genetic damage. The
      purpose of this study was to evaluate occupational exposure to TCE, by analysis
      of the air in the breathing zone and of urine from workers employed in a clock
      manufacturing factory. A subjective symptom survey was conducted by using a self
      administered questionnaire to evaluate the health hazards. Micronucleus (MN)
      frequency, based on the cytokinesis-block micronucleus assay (CBMN) in peripheral
      blood lymphocytes, (PBLs) was used as a biomarker for chromosome damage. A total
      of 244 participants, including 171 workers occupationally exposed to TCE and 73
      non-exposed control employees, working mainly in office jobs in the same factory,
      were enrolled in this study. Analyses of airborne TCE concentrations in the
      workplace, and of urinary trichloroacetic acid (TCA) of the workers and controls,
      were performed by Gas Chromatography-Electron Capture Detector (GC-ECD) using the
      modified headspace technique. The average concentration of TCE in the workplace
      breathing zone was 27.83 +/- 6.02 ppm. The average level of urinary TCA of the
      exposed workers and controls was 14.84 +/- 1.62, 2.95 +/- 0.28 mg/L. The
      frequency of MN/1000BN was 7.029 +/- 0.39, significantly higher than for those in
      the control group (3.57 +/- 0.31, p = 0.001). According to multiple linear
      regression analysis, the results indicated that urinary TCA levels correlated
      with the increased MN in exposed workers (r = 0.285, p < 0.001). The prevalence
      rate of subjective symptoms in the exposed group was 9.61-11.76 times higher than
      the rate of the non-exposed group (p < 0.001). It was found that skin (29.6%) and
      respiratory symptoms (21.1%) were the most frequent among the exposed workers. In
      conclusion, these results indicate that increased micronucleus frequency is
      associated with occupational trichloroethylene exposure. The use of TCE in the
      factory is threatening workers' health. 

PMID- 25560357
TI  - The evaluation of time performance in the emergency response center to provide
      pre-hospital emergency services in Kermanshah.
AB  - This study evaluated the time performance in the emergency response center to
      provide pre-hospital emergency services in Kermanshah. This study was a
      descriptive retrospective cross-sectional study. In this study 500 cases of
      patients from Shahrivar (September) 2012 to the end of Shahrivar (September) 2013
      were selected and studied by the non-probability quota method. The measuring tool
      included a preset cases record sheet and sampling method was completing the cases
      record sheet by referring to the patients' cases. Data were analyzed using SPSS
      version 18 and the concepts of descriptive and inferential statistics (Kruskal
      Wallis test, benchmark Eta (Eta), Games-Howell post hoc test). The results showed
      that the interval mean between receiving the mission to reaching the scene,
      between reaching the scene to moving from the scene, and between moving from the
      scene to a health center was 7.28, 16.73 and 7.28 minutes. The overall mean of
      time performance from the scene to the health center was 11.34 minutes. Any
      intervention in order to speed up service delivery, reduce response times,
      ambulance equipment and facilities required for accuracy, validity and
      reliability of the data recorded in the emergency dispatch department, Continuing
      Education of ambulance staffs, the use of manpower with higher specialize levels
      such as nurses, supply the job satisfaction, and increase the coordination with
      other departments that are somehow involved in this process can provide the
      ground for reducing the loss and disability resulting from traffic accidents. 

PMID- 25560358
TI  - Comparison of lifestyle in women with polycystic ovary syndrome and healthy
      women.
AB  - Given the high prevalence of polycystic ovary syndrome (PCOS), and that a
      lifestyle is recognized effective in development of many diseases, this study
      aimed to compare lifestyle of women with PCOS and healthy women. Nor are there
      sufficient studies on the difference between lifestyle of these people with that
      of healthy people. Furthermore, studies show that changes in lifestyle improve
      this disease. This descriptive-comparative study was conducted on 65 women with
      PCOS and 65 healthy women of 18 to 45 years old who presented to hospitals
      affiliated to Shahid Beheshti University of Medical Sciences in 2013. The
      subjects were selected using multi stage random sampling method. The data were
      collected using questionnaires for diet, International Physical Activity
      Questionnaire, and unhealthy behaviors and were analyzed in SPSS v. 17, using
      descriptive statistics, Man-Whitney, independent t, Chi-square and logistic
      regression tests. The results showed there was a significant relationship between
      PCOS and inappropriate diet (p=0.009), low physical activity (p=0.009), but no
      relationship was observed between PCOS and unhealthy behaviors. Given the results
      obtained, training and awareness raising is necessary for women and girls
      especially about appropriate diet and regular physical activity. 

PMID- 25560359
TI  - Analysis of developmental level of counties of Fars in terms of health
      infrastructure indicators using standardized scores pattern approach and factor
      analysis.
AB  - INTRODUCTION: It is necessary for planning in order to achieve optimal
      development, to have knowledge and understanding of the current situation. This
      identification requires separate areas of study into planning and assessing
      regions of each area with development indicators and analysis and ranking each
      area in terms of having gifts of development. The study also aims to analyze the
      development level of counties of Fars in terms of health infrastructure
      indicators using standardized scores pattern and factor analysis. METHODS: This
      is a descriptive and applied study, which has discussed the levels of 29 counties
      of Fars based on 10 health selected indicators using a standardized scoring
      model. Data were collected using a data collection form developed by the
      researchers through the Center of Statistics and Shiraz University of Medical
      Sciences. Results were analyzed using Excel and SPSS 19. RESULTS: Based on
      calculations according to standardized score and factor analysis methods, Shiraz
      and Rostam had the most and the least level between the other cities,
      respectively. Also development coefficient and operating score of the studied
      counties ranged from a maximum of 0.894 to a minimum of -0.941, and a maximum of
      3.861 to a minimum of 2.001, respectively. DISCUSSION: There are relatively large
      differences between different counties in healthcare sector, and most studied
      counties in terms of healthcare sector indicators are not satisfactory. So
      planning how to allocate healthcare resources from policy makers to improve the
      studied counties is essential.

PMID- 25560360
TI  - Using creative problem solving (TRIZ) in improving the quality of hospital
      services.
AB  - TRIZ is an initiative and SERVQUAL is a structured methodology for quality
      improvement. Using these tools, inventive problem solving can be applied for
      quality improvement, and the highest quality can be reached using creative
      quality improvement methodology. The present study seeks to determine the
      priority of quality aspects of services provided for patients in the hospital as
      well as how TRIZ can help in improving the quality of those services. This Study
      is an applied research which used a dynamic qualitative descriptive survey method
      during year 2011. Statistical population includes every patient who visited in
      one of the University Hospitals from March 2011. There existed a big gap between
      patients' expectations from what seemingly is seen (the design of the hospital)
      and timely provision of services with their perceptions. Also, quality aspects of
      services were prioritized as follows: keeping the appearance of hospital (the
      design), accountability, assurance, credibility and having empathy. Thus, the
      only thing which mattered most for all staff and managers of studied hospital was
      the appearance of hospital as well as its staff look. This can grasp a high
      percentage of patients' satisfaction. By referring to contradiction matrix, the
      most important principles of TRIZ model were related to tangible factors
      including principles No. 13 (discarding and recovering), 25 (self-service), 35
      (parameter changes), and 2 (taking out). Furthermore, in addition to these four
      principles, principle No. 24 (intermediary) was repeated most among the others.
      By utilizing TRIZ, hospital problems can be examined with a more open view, Go
      beyond The conceptual framework of the organization and responded more quickly to
      patients ' needs. 

PMID- 25560361
TI  - Treatment-seeking behaviour and social health insurance in Africa: the case of
      Ghana under the National Health Insurance Scheme.
AB  - Health insurance is attracting more and more attention as a means for improving
      health care utilization and protecting households against impoverishment from out
      of-pocket expenditures. Currently about 52 percent of the resources for financing
      health care services come from out of pocket sources or user fees in Africa.
      Therefore, Ghana serves as in interesting case study as it has successfully
      expanded coverage of the National Health Insurance Scheme (NHIS). The study aims
      to establish the treatment-seeking behaviour of households in Ghana under the NHI
      policy. The study relies on household data collected from three districts in
      Ghana covering the 3 ecological zones namely the coastal, forest and savannah.Out
      of the 1013 who sought care in the previous 4 weeks, 60% were insured and 71% of
      them sought care from a formal health facility. The results from the multinomial
      logit estimations show that health insurance and travel time to health facility
      are significant determinants of health care demand. Overall, compared to the
      uninsured, the insured are more likely to choose formal health facilities than
      informal care including self-medication when ill. We discuss the implications of
      these results as the concept of the NHIS grows widely in Ghana and serves as a
      good model for other African countries. 

PMID- 25560362
TI  - Attitudes and practices of complementary and alternative medicine among
      adolescents in Saudi Arabia.
AB  - The aim of this study was to investigate the attitudes and use of complementary
      and alternative medicine (CAM) among Saudi Arabian adolescents. A multistage
      stratified sampling method was used to select 736 adolescents (358 males, 378
      females) aged 15-19 years from secondary schools. The study was carried out in Al
      Khobar city, Eastern region of Saudi Arabia. The findings revealed that the use
      of CAM by adolescents in their lifetime ranged from 1.6% for acupuncture to 58.6%
      for honey treatment, with significant differences between genders, except in the
      use of dietary supplements, black cumin, and acupuncture therapies. Females were
      more likely to use CAM for treating abdominal pains, cold and flu, and cough than
      males (P < 0.000). Family members and friends (67.7%) were the main source of CAM
      usage, followed by television (10%), and Internet (8%). Religious and medicinal
      herb healers were the CAM healers most commonly visited by adolescents. Nearly 21
      43% of adolescents had positive attitudes toward CAM, with some significant
      differences between males and females. It can be concluded that CAM is widely
      used by Saudi adolescents, but caution should be exercised for the safe usage of
      some CAM treatments. CAM should not be ignored; however there is an urgent need
      to establish regulations for CAM usage. 

PMID- 25560363
TI  - Evaluation of maternal mortality cases in the province of Elazig, Turkey, 2007
      2013: a retrospective study.
AB  - The aim of this study was to determine the causes and factors influencing
      maternal mortality. All maternal deaths occurring between January 2007 and
      November 2013 in the Elazig Province of Turkey were retrospectively investigated.
      The maternal age, obstetric history, cause of death, encountered delay model of
      each case, as well as the overall number of annual live births in the Province
      were determined. The information of cases was obtained from Directorate of Public
      Health and hospital records.  Families or family doctors were also interviewed to
      obtain details about the circumstances surrounding each death. There were a total
      of 64,423 live births in the Province of Elazig between 2007- 2013. The number
      and ratio of maternal deaths due to direct and indirect causes were 12 and 18.6,
      respectively. The direct causes of maternal death were hypertensive diseases of
      pregnancy (n=5, 41.7%), obstetric hemorrhages (n=3, 25%) and pulmonary embolism
      (n=1, 8.3%). The indirect causes of death were cardiac diseases (n=2, 16.7%) and
      malignancy (n=1, 8.3%). When classified according to the "Three Delays Model", 2
      cases were in the first delay model and 3 cases in the third delay model; the
      second delay model led to no maternal deaths. Hypertensive diseases of pregnancy
      are the leading cause of maternal mortality in our province. The preventable
      causes of maternal mortality and factors contributing to death must be identified
      to reduce the incidence. 

PMID- 25560364
TI  - Identification and analysis of labor productivity components based on ACHIEVE
      model (case study: staff of Kermanshah University of Medical Sciences).
AB  - Identification and analysis of the components of labor productivity based on
      ACHIEVE model was performed among employees in different parts of Kermanshah
      University of Medical Sciences in 2014. This was a descriptive correlational
      study in which the population consisted of 270 working personnel in different
      administrative groups (contractual, fixed- term and regular) at Kermanshah
      University of Medical Sciences (872 people) that were selected among 872 people
      through stratified random sampling method based on Krejcie and Morgan sampling
      table. The survey tool included labor productivity questionnaire of ACHIEVE.
      Questionnaires were confirmed in terms of content and face validity, and their
      reliability was calculated using Cronbach's alpha coefficient. The data were
      analyzed by SPSS-18 software using descriptive and inferential statistics. The
      mean scores for labor productivity dimensions of the employees, including
      environment (environmental fit), evaluation (training and performance feedback),
      validity (valid and legal exercise of personnel), incentive (motivation or
      desire), help (organizational support), clarity (role perception or
      understanding), ability (knowledge and skills) variables and total labor
      productivity were 4.10+/-0.630, 3.99+/-0.568, 3.97+/-0.607, 3.76+/-0.701, 3.63+/
      0.746, 3.59+/-0.777, 3.49+/-0.882 and 26.54+/-4.347, respectively. Also, the
      results indicated that the seven factors of environment, performance assessment,
      validity, motivation, organizational support, clarity, and ability were effective
      in increasing labor productivity. The analysis of the current status of
      university staff in the employees' viewpoint suggested that the two factors of
      environment and evaluation, which had the greatest impact on labor productivity
      in the viewpoint of the staff, were in a favorable condition and needed to be
      further taken into consideration by authorities.

PMID- 25560365
TI  - Quantification of protein-materials interaction by soft colloidal probe
      spectroscopy.
AB  - We present a robust and fast method to quantify the adhesion energy of surface
      anchored proteins on material surfaces using soft colloidal particles as sensors.
      The results obtained from studying the adhesion of fibronectin on surfaces with
      different hydrophobicity were in good agreement with theoretical considerations
      demonstrating the feasibility of the method. 

PMID- 25560366
TI  - Assessment of two e-learning methods teaching undergraduate students cephalometry
      in orthodontics.
AB  - AIM: Cephalometry is important for orthodontic diagnosis and treatment planning
      and is part of the core curriculum for training dentists. Training involves
      identifying anatomical landmarks. The aim of this investigation was to assess
      whether e-learning improves learning efficiency; a programme specifically
      designed for this purpose was compared to commercially available software.
      METHODS: Thirty undergraduate students underwent traditional training of
      cephalometry consisting of lectures and tutorials. Tracing skills were tested
      immediately afterwards (T0). The students were then randomly allocated to three
      groups: 10 students served as control (CF); they were asked to improve their
      skills using the material provided so far. Ten students were given a program
      specifically designed for this study that was based on a power point presentation
      (PPT). The last group was given a commercially available program that included
      teaching elements (SW). The groups were tested at the end the six week training
      (T1). The test consisted of tracing 30 points on two radiographs and a point
      score improvement was calculated. The students were interviewed after the second
      test. RESULTS: Both e-learning groups improved more than the traditional group.
      Improvement scores were four for CF; 8.6 for PPT and 2.8 for SW. For PPT all
      participants improved and the student feedback was the best compared to the other
      groups. For the other groups some candidates worsened. CONCLUSIONS: Blended
      learning produced better learning outcomes compared to using a traditional
      teaching method alone. The easy to use Power Point based custom software produced
      better results than the commercially available software.

PMID- 25560367
TI  - Kinetics of dispersion of nanoparticles in thin polymer films at high
      temperature.
AB  - We report the first detailed study of the kinetics of dispersion of nanoparticles
      in thin polymer films using temperature dependent in situ X-ray scattering
      measurements. We show a comparably enhanced dispersion at higher temperatures for
      systems which are otherwise phase segregated at room temperature. Detailed
      analysis of the time dependent X-ray reflectivity and diffuse scattering data
      allows us to explore the out-of-plane and in-plane mobility of the nanoparticles
      in the polymer films. While the out-of-plane motion is diffusive with a diffusion
      coefficient almost two orders of magnitude lower than that expected in bulk
      polymer, the in-plane one is found to be super-diffusive resulting in
      significantly larger in-plane displacement at similar time scales. We discuss the
      origin of the observed highly anisotropic motion of nanoparticles due to their
      slaved motion with respect to the anisotropic chain orientation and consequent
      diffusivity anisotropy of matrix chains. We also suggest strategies to utilize
      these observations to kinetically improve dispersion in otherwise
      thermodynamically segregated polymer nanocomposite films. 

PMID- 25560368
TI  - Inhibition of recombinase polymerase amplification by background DNA: a lateral
      flow-based method for enriching target DNA.
AB  - Recombinase polymerase amplification (RPA) may be used to detect a variety of
      pathogens, often after minimal sample preparation. However, previous work has
      shown that whole blood inhibits RPA. In this paper, we show that the
      concentrations of background DNA found in whole blood prevent the amplification
      of target DNA by RPA. First, using an HIV-1 RPA assay with known concentrations
      of nonspecific background DNA, we show that RPA tolerates more background DNA
      when higher HIV-1 target concentrations are present. Then, using three additional
      assays, we demonstrate that the maximum amount of background DNA that may be
      tolerated in RPA reactions depends on the DNA sequences used in the assay. We
      also show that changing the RPA reaction conditions, such as incubation time and
      primer concentration, has little effect on the ability of RPA to function when
      high concentrations of background DNA are present. Finally, we develop and
      characterize a lateral flow-based method for enriching the target DNA
      concentration relative to the background DNA concentration. This sample
      processing method enables RPA of 10(4) copies of HIV-1 DNA in a background of 0
      14 MUg of background DNA. Without lateral flow sample enrichment, the maximum
      amount of background DNA tolerated is 2 MUg when 10(6) copies of HIV-1 DNA are
      present. This method requires no heating or other external equipment, may be
      integrated with upstream DNA extraction and purification processes, is compatible
      with the components of lysed blood, and has the potential to detect HIV-1 DNA in
      infant whole blood with high proviral loads. 

PMID- 25560369
TI  - Training for the future NHS: training junior doctors in the United Kingdom within
      the 48-hour European working time directive.
AB  - Since August 2009, the National Health Service of the United Kingdom has faced
      the challenge of delivering training for junior doctors within a 48-hour working
      week, as stipulated by the European Working Time Directive and legislated in the
      UK by the Working Time Regulations 1998. Since that time, widespread concern has
      been expressed about the impact of restricted duty hours on the quality of
      postgraduate medical training in the UK, particularly in the "craft" specialties-
      that is, those disciplines in which trainees develop practical skills that are
      best learned through direct experience with patients. At the same time,
      specialist training in the UK has experienced considerable change since 2007 with
      the introduction of competency-based specialty curricula, workplace-based
      assessment, and the annual review of competency progression. The challenges
      presented by the reduction of duty hours include increased pressure on doctors-in
      training to provide service during evening and overnight hours, reduced
      interaction with supervisors, and reduced opportunities for learning. This paper
      explores these challenges and proposes potential responses with respect to the
      reorganization of training and service provision.

PMID- 25560370
TI  - Semaphorin 3A serum levels are influenced by haemodialysis: what clinical
      significance?
AB  - AIM: Semaphorin 3A urinary levels represent an early, predictive biomarker of
      acute kidney injury and positively correlate with albumin-to-creatinine ratio and
      serum creatinine in hypertensive patients with chronic kidney disease. Our
      purpose has been to evaluate semaphorin 3A serum levels in a cohort of
      haemodialysis (HD) patients, the influence of a single HD session on its
      concentrations, and the potential correlation with clinical and biochemical
      parameters. METHODS: We enrolled 18 patients receiving HD with Acetate-Free
      Biofiltration technique and 16 healthy subjects as controls. Peripheral venous
      blood samples were obtained from patients at different intervals: start of
      dialysis (pre-HD), middle, and end of the treatment (post-HD). We also collected
      dialysate samples by the Quantiscan monitoring system (Hospal, Bologna, Italy).
      RESULTS: Semaphorin 3A was significantly lower in HD patients at baseline
      compared to controls (median 19.50 (interquartile range 1.00-65.00) versus 97.50
      (23.50-161.00) ng/mL, P = 0.0237). A statistically significant reduction was seen
      during a single HD session (from 19.50 (1.00-65.00) to 0.86 (0.82-4.21) ng/mL, P
      < 0.0001), with a reduction ratio of 65.92 +/- 33.51%. The median concentration
      in dialysate was 54.00 (15.00-102.00) ng/mL. Pre-HD values were directly related
      to serum vitamin D (r = 0.872; P = 0.001) and inversely correlated with calcium
      levels (r = -0.426; P = 0.012) and calcium * phosphate product (r = -0.422; P =
      0.0252). CONCLUSION: Semaphorin 3A removal during HD may be clinically relevant
      due to its involvement in different aspects of cell physiology and in bone
      remodelling. Semaphorin 3A both inhibits osteoclastic bone reabsorption and
      increases osteoblastic new bone formation, thus playing a dual osteoprotective
      role.

PMID- 25560371
TI  - Evaluating health services with point of service feedback: perspectives and
      experiences of patients, staff and community volunteers in an inpatient
      rehabilitation facility.
AB  - PURPOSE: To determine patient, staff and community volunteer opinions and
      experiences of point of service feedback (POSF) in an inpatient rehabilitation
      facility. METHOD: Participants were recruited by purposeful sampling. Two
      researchers conducted in-depth semi-scripted interviews with patients, staff or
      volunteers until no new issues emerged. Manually transcribed interview data
      underwent thematic analysis that grouped information into categories of related
      information. RESULTS: Twenty patients, 26 staff from 10 different professional
      groups, and 2 community volunteers were interviewed. Patient and volunteer data
      were grouped into five main categories: patients wanted their voice heard and
      acted on; patients could be positively and negatively affected by POSF; patients
      could be reluctant to evaluate staff; patients preferred POSF to post-discharge
      mailed questionnaires; and patients' feedback was influenced by the data
      collector. Staff wanted: feedback to help them improve the patient experience;
      and feedback that was trustworthy, usable and used. Staff believed that the
      feedback-collector influenced patients' feedback and affected how feedback could
      be used. CONCLUSIONS: Patients, staff and community volunteers identified issues
      that determine the appropriateness and usefulness of POSF. Policy and practise
      should address the preferences, needs and experiences of health service users and
      providers so that POSF produces maximum benefits for both patients and health
      services. Implications for Rehabilitation POSF can enhance patients' experiences
      of inpatient rehabilitation by providing a mechanism to be heard and
      communicating that patients are valued; care must be exercised with patients who
      find giving feedback stressful. Collecting POSF is most beneficial when coupled
      with methods to efficiently and effectively respond to feedback. POSF requires
      interpretation in light of its limitations including patients' ability to
      accurately and unreservedly communicate their experiences. Who collects POSF
      requires careful consideration; community volunteers have both advantages and
      disadvantages.

PMID- 25560372
TI  - Effect of ambient PM(2.5) on lung mitochondrial damage and fusion/fission gene
      expression in rats.
AB  - Exposure to ambient fine particulate matter (PM2.5) increases the risk of
      respiratory disease. Although previous mitochondrial research has provided new
      information about PM toxicity in the lung, the exact mechanism of PM2.5-mediated
      structural and functional damage of lung mitochondria remains unclear. In this
      study, changes in lung mitochondrial morphology, expression of mitochondrial
      fission/fusion markers, lipid peroxidation, and transport ATPase activity in SD
      rats exposed to ambient PM2.5 at different dosages were investigated. Also, the
      release of reactive oxygen species (ROS) via the respiratory burst in rat
      alveolar macrophages (AMs) exposed to PM2.5 was examined by luminol-dependent
      chemiluminescence (CL). The results showed that (1) PM2.5 deposited in the lung
      and induced pathological damage, particularly causing abnormal alterations of
      mitochondrial structure, including mitochondrial swelling and cristae disorder or
      even fragmentation in the presence of higher doses of PM2.5; (2) PM2.5
      significantly affected the expression of specific mitochondrial fission/fusion
      markers (OPA1, Mfn1, Mfn2, Fis1, and Drp1) in rat lung; (3) PM2.5 inhibited Mn
      superoxide dismutase (MnSOD), Na(+)K(+)-ATPase, and Ca(2+)-ATPase activities and
      elevated malondialdehyde (MDA) content in rat lung mitochondria; and (4) PM2.5
      induced rat AMs to produce ROS, which was inhibited by about 84.1% by
      diphenyleneiodonium chloride (DPI), an important ROS generation inhibitor. It is
      suggested that the pathological injury observed in rat lung exposed to PM2.5 is
      associated with mitochondrial fusion-fission dysfunction, ROS generation,
      mitochondrial lipid peroxidation, and cellular homeostasis imbalance. Damage to
      lung mitochondria may be one of the important mechanisms by which PM2.5 induces
      lung injury, contributing to respiratory diseases. 

PMID- 25560374
TI  - Peripheral artery disease: Laser light show--targeting in-stent restenosis in
      peripheral arteries with excimer laser atherectomy.

PMID- 25560373
TI  - Direct chiral resolution of underivatized amino acids on a stationary phase
      dynamically modified with the ion-exchanger N(tau) -decyl-L-spinacine.
AB  - Increasing attention has been devoted in the last decades to chiral
      chromatography, principally to high-performance liquid chromatography techniques
      using a chiral stationary phase. Many chiral high-performance liquid
      chromatography columns are commercially available, but, unfortunately, they are
      most often rather expensive. A cheap alternative to the commercial chiral columns
      is the dynamic-coating procedure of a standard achiral stationary phase with a
      chiral selector containing both a chiral domain and a chain or a group able to
      tightly (but noncovalently) bind the achiral support. This is the case of N(tau) 
      decyl-l-spinacine, already successfully employed to dynamically cover a reversed
      phase column to separate racemic mixtures of amino acids through the ligand
      exchange mechanism. In the present work, the same chiral selector is employed to
      separate racemic mixtures of amino acids and oligopeptides, in the absence of
      metal ions: no coordination complex is formed, but only electrostatic and weak
      nonbonding interactions between the chiral phase and the analytes are responsible
      for the observed enantioselectivity. The new method is simpler than the previous
      one, very effective in the case of aromatic amino acids and oligopeptides and
      also suitable for preparative purposes. 

PMID- 25560375
TI  - Heart failure therapies in 2014: Mixed results for heart failure therapies.

PMID- 25560376
TI  - Acute coronary syndromes: Prehospital therapy for STEMI.

PMID- 25560377
TI  - Heart failure: Thoracic spinal cord stimulation for the treatment of HF.

PMID- 25560379
TI  - PCI and CABG surgery in 2014: CABG surgery versus PCI in CAD--surgery strikes
      again!

PMID- 25560378
TI  - Diuretic response in acute heart failure-pathophysiology, evaluation, and
      therapy.
AB  - The administration of loop diuretics to achieve decongestion is the cornerstone
      of therapy for acute heart failure. Unfortunately, impaired response to diuretics
      is common in these patients and associated with adverse outcomes. Diuretic
      resistance is thought to result from a complex interplay between cardiac and
      renal dysfunction, and specific renal adaptation and escape mechanisms, such as
      neurohormonal activation and the braking phenomenon. However, our understanding
      of diuretic response in patients with acute heart failure is still limited and a
      uniform definition is lacking. Three objective methods to evaluate diuretic
      response have been introduced, which all suggest that diuretic response should be
      determined based on the effect of diuretic dose administered. Several strategies
      have been proposed to overcome diuretic resistance, including combination therapy
      and ultrafiltration, but prospective studies in patients who are truly
      unresponsive to diuretics are lacking. An enhanced understanding of diuretic
      response should ultimately lead to an improved, individualized approach to
      treating patients with acute heart failure. 

PMID- 25560381
TI  - FDA regulation of laboratory-developed diagnostic tests: protect the public,
      advance the science.

PMID- 25560380
TI  - Treatment of symptomatic coronary artery disease in patients with end-stage renal
      disease on hemodialysis with paclitaxel-eluting TAXUS stent.
AB  - Percutaneous coronary intervention (PCI) utilizing drug-eluting stents is
      becoming a very common revascularization technique in the dialysis cohort;
      therefore, we sought to identify the impact of dialysis on outcomes in this group
      of patients. This is a multicenter registry comparing results of 290 patients
      (186 with normal kidney function, 104 on dialysis) who underwent PCI with
      exclusive use of paclitaxel-eluting TAXUS stent. The primary endpoint was an
      assessment of major adverse cardiac events (MACE) at 1- and 2-year observation.
      Mean follow-up was 23.3 +/- 6.1 months. Results at 12 months showed: MACE 11.8%
      vs. 7.7% (P = not significant [ns]), composite major adverse cardiac and
      cerebrovascular events (MACCE) 12.4% vs. 11.5% (P = ns), all-cause death 2.7% vs.
      8.6% (P < 0.05), cardiac death 2.7% vs. 1.9% (P = ns), target vessel
      revascularization (TVR) 9.1% vs. 6.7% (P = ns), acute myocardial infarction (AMI)
      3.8% vs. 2.9% (P = ns), cerebrovascular events (CVA) 0.5% vs. 1.0% (P = ns); and
      results at 24 months showed: MACE 17.7% vs. 18.3% (P = ns), MACCE 21.5% vs. 26.0%
      (P = ns), all-cause death 4.3% vs. 14.4% (P < 0.01), cardiac death 3.2% vs. 1.9%
      (P = ns), TVR 14.0% vs. 16.3% (P = ns), AMI 5.4% vs. 5.8% (P = ns), CVA 3.2% vs.
      2.9% (P = ns) for non-end-stage renal disease (ESRD) and dialysis group,
      respectively. Prior coronary artery bypass graft (CABG) was found to be single
      risk factor for MACE, TVR, and MACCE in patients with ESRD, while dialysis and
      prior CABG were found to be single risk factors for death in the entire
      population. PCI with TAXUS is a feasible procedure and presents promising results
      in dialysis-dependent patients. 

PMID- 25560382
TI  - Dynamics of enhancers in myeloid antigen presenting cells upon LPS stimulation.
AB  - BACKGROUND: Recent studies have underscored the role of enhancers in defining
      cell type-specific transcriptomes. Cell type-specific enhancers are bound by
      combinations of shared and cell type-specific transcription factors (TFs).
      However, little is known about combinatorial binding of TFs to enhancers,
      dynamics of TF binding following stimulation, or the downstream effects on gene
      expression. Here, we address these questions in two types of myeloid antigen
      presenting cells (APCs), macrophages and dendritic cells (DCs), before and after
      stimulation with lipopolysaccharide (LPS), a potent stimulator of the innate
      immune response. RESULTS: We classified enhancers according to the combination of
      TFs binding them. There were significant correlations between the sets of TFs
      bound to enhancers prior to stimulation and expression changes of nearby genes
      after stimulation. Importantly, a set of enhancers pre-bound by PU.1, C/EBPbeta,
      ATF3, IRF4, and JunB was strongly associated with induced genes and binding by
      stimulus-activated regulators. Our classification suggests that transient loss of
      ATF3 binding to a subset of these enhancers is important for regulation of early
      induced genes. Changes in TF-enhancer binding after stimulation were correlated
      with binding by additional activated TFs and with the presence of proximally
      located enhancers. CONCLUSIONS: The results presented in this study reveal the
      complexity and dynamics of TF- enhancer binding before and after stimulation in
      myeloid APCs.

PMID- 25560384
TI  - Trapping of microwave radiation in hollow polypyrrole microsphere through
      enhanced internal reflection: a novel approach.
AB  - In present work, spherical core (polystyrene, PS)/shell (polypyrrole, PPy) has
      been synthesized via in situ chemical oxidative copolymerization of pyrrole (Py)
      on the surface of sulfonated PS microsphere followed by the formation of hollow
      polypyrrole (HPPy) shell by dissolving PS inner core in THF. Thereafter, we first
      time established that such fabricated novel art of morphology acts as a
      conducting trap in absorbing electromagnetic (EM) wave by internal reflection.
      Further studies have been extended on the formation of its silver nanocomposites
      HPPy/Ag to strengthen our contention on this novel approach. Our investigations
      showed that electromagnetic interference (EMI) shielding efficiency (SE) of HPPy
      (34.5-6 dB) is significantly higher compared to PPy (20-5 dB) in the frequency
      range of 0.5-8 GHz due to the trapping of EM wave by internal reflection. We also
      observed that EMI shielding is further enhanced to 59-23 in 10 wt% Ag loaded
      HPPy/Ag-10. This is attributed to the simultaneous contribution of internal
      reflection as well as reflection from outer surface. Such high EMI shielding
      capacity using conducting polymers are rarely reported. 

PMID- 25560383
TI  - Molecular, anatomical and functional changes in the retinal ganglion cells after
      optic nerve crush in mice.
AB  - PURPOSE: Optic nerve crush (ONC) and subsequent axonal damage can be used in
      rodents to study the mechanism of retinal ganglion cell (RGC) degeneration. Here,
      we examined electroretinograms (ERGs) in post-ONC mice to investigate changes in
      the positive scotopic threshold response (pSTR). We then compared these changes
      with molecular and morphological changes to identify early objective biomarkers
      of RGC dysfunction. METHODS: Fifty 12-week-old C57BL/6 mice were included. ONC
      was used to induce axonal injury in the right eye of each animal, with the left
      eye used as a control. The expression of the RGC markers Brn3a and Brn3b was
      measured on days 1, 2, 3, 5 and 7 after ONC with quantitative real-time PCR. ERGs
      were recorded under dark adaptation with the stimulus intensity increasing from 
      6.2 to 0.43 log cd-s/m(2) on days 1, 2, 3, 5, 7 and 10 after ONC. The pSTR, a-
      and b-wave amplitudes were measured. Inner retinal thickness around the optic
      nerve head was measured with spectral-domain optical coherence tomography on days
      0, 2, 5, 7 and 10 after ONC. RESULTS: The expression of Brn3a and Brn3b began to
      significantly decrease on day 1 and day 2, respectively (P < 0.01). The amplitude
      of the pSTR underwent rapid, significant deterioration on day 3, after which it
      fell gradually (P < 0.01), while the a- and b-wave amplitudes remained unchanged
      throughout the experiment. Inner retinal thickness gradually decreased, with the
      most significant reduction on day 10 (P < 0.01). CONCLUSIONS: Decrease in pSTR
      likely reflected the early loss of RGC function after ONC and that declining
      expression of RGC-specific genes preceded anatomical and functional changes in
      the RGCs.

PMID- 25560386
TI  - Intrasellar pilocytic astrocytomas: clinical, imaging, pathological, and surgical
      findings.
AB  - A pilocytic astrocytoma is not usually considered in the differential diagnosis
      of an intrasellar tumor. An awareness of this tumor as primarily an intrasellar
      entity is important to avoid confusion during its diagnosis. We retrospectively
      examined the records of 631 patients treated at our institution between 2006 and
      2010 who underwent transsphenoidal resection of pituitary tumors and identified
      those diagnosed with pilocytic astrocytoma. We excluded patients who harbored a
      pituicytoma. We also searched the literature for patients with a histologically
      confirmed diagnosis of intrasellar pilocytic astrocytoma. Only two patients in
      our series harbored intrasellar tumors and had a histologic diagnosis of
      pilocytic astrocytoma. We also found two other cases in the literature that met
      our criteria. Pilocytic astrocytoma should be considered in the differential
      diagnosis of an intrasellar lesion. An understanding of this tumor's radiological
      features can avoid diagnostic confusion. 

PMID- 25560385
TI  - Abyssomicin 2 reactivates latent HIV-1 by a PKC- and HDAC-independent mechanism.
AB  - Screening of a marine natural products library afforded three new analogues of
      the tetronic acid containing polyketide abyssomicin family and identified
      abyssomicin 2 as a selective reactivator of latent HIV virus. Examination of the
      mode of action of this new latent HIV reactivating agent demonstrated that it
      functions via a distinct mechanism compared to that of existing reactivating
      agents and is effective at reactivating latent virus in a subset of primary
      patient cell lines. 

PMID- 25560387
TI  - Tumor resection with carmustine wafer placement as salvage therapy after local
      failure of radiosurgery for brain metastasis.
AB  - Prolonged survival in brain metastasis patients increases recurrence rates and
      places added importance on salvage therapies. Research examining carmustine
      polymer wafers as an adjuvant therapy for brain metastasis is limited. We present
      a single institution retrospective series documenting the use of BCNU wafers
      placed in the cavity of resected recurrent brain metastases that had failed prior
      stereotactic radiosurgery (SRS). Between February 2002 and April 2013, a total of
      31 patients with brain metastases failed SRS and underwent resection with
      intracavitary placement of carmustine wafers. Clinical outcomes including local
      control, survival, cause of death, and toxicity were determined from electronic
      medical records. Kaplan-Meier analysis was performed to assess local control and
      survival. Imaging features were reviewed and described for patients with serial
      post-operative follow-up imaging examinations over time. Overall survival at 6
      months and 12 months was 63% and 36%, respectively. Fourteen of 31 patients (45%)
      died from neurologic causes. Local control within the resection cavity was 87%
      and 70% at 6 and 12 months, respectively. Five patients (16%) underwent further
      salvage therapy following carmustine wafer placement after local failure.
      Resection cavities of all six patients with follow-up imaging showed linear
      peripheral enhancement. Pericavity and wafer enhancement was present as early as
      the same day as surgery and persisted in all cases to 6 months or longer.
      Carmustine polymer wafers are an effective salvage treatment following resection
      of a brain metastasis that has failed prior SRS. For patients with successful
      local control after wafer implantation, linear enhancement at the cavity is
      common.

PMID- 25560388
TI  - Effects of new Ab initio rate coefficients on predictions of species formed
      during n-butanol ignition and pyrolysis.
AB  - Experimental, time-resolved species profiles provide critical tests in developing
      accurate combustion models for biofuels such as n-butanol. A number of such
      species profiles measured by Karwat et al. [ Karwat, D. M. A.; et al. J. Phys.
      Chem. A 2011 , 115 , 4909 ] were discordant with predictions from a well-tested
      chemical kinetic mechanism developed by Black et al. [ Black, G.; et al. Combust.
      Flame 2010 , 157 , 363 ]. Since then, significant theoretical and experimental
      efforts have focused on determining the rate coefficients of primary n-butanol
      consumption pathways in combustion environments, including H atom abstraction
      reactions from n-butanol by key radicals such as HO2 and OH, as well as the
      decomposition of the radicals formed by these H atom abstractions. These
      reactions not only determine the overall reactivity of n-butanol, but also
      significantly affect the concentrations of intermediate species formed during n
      butanol ignition. In this paper we explore the effect of incorporating new ab
      initio predictions into the Black et al. mechanism on predictions of ignition
      delay time and species time histories for the experimental conditions studied by
      Karwat et al. The revised predictions for the intermediate species time histories
      are in much improved agreement with the measurements, but some discrepancies
      persist. A rate of production analysis comparing the effects of various
      modifications to the Black et al. mechanism shows significant changes in the
      predicted consumption pathways of n-butanol, and of the hydroxybutyl and butoxy
      radicals formed by H atom abstraction from n-butanol. The predictions from the
      newly revised mechanism are in very good agreement with the low-pressure n
      butanol pyrolysis product species measurements of Stranic et al. [ Stranic, I.;
      et al. Combust. Flame 2012 , 159 , 3242 ] for all but one species. Importantly,
      the changes to the Black et al. mechanism show that concentrations of small
      products from n-butanol pyrolysis are sensitive to different reactions than those
      presented by Stranic et al. 

PMID- 25560390
TI  - Sources of marital conflict in five cultures.
AB  - This analysis of previously collected data examined four fitness-relevant issues
      for their possible role in marital conflict. These were sex, finances, division
      of labor, and raising children, selected in light of their pertinence to sex
      differences in reproductive strategies. Over 2,000 couples in five diverse
      cultures were studied. Marital conflict was assessed by the Problems with Partner
      scale, which was previously shown to demonstrate measurement invariance across
      cultures and genders. All four issues were significantly related to perceived
      marital problems in almost all cases. Thus, conflict tended to arise around
      issues relevant to reproductive strategies. A few cultural idiosyncrasies emerged
      and are discussed. In all cultures, wives reported more problems than husbands.
      Another important issue was kindness. The results suggest that a key factor in
      marital success or failure may be kindness necessary to sustain this prolonged
      and intimate relationship of cooperation for raising one's offspring. 

PMID- 25560389
TI  - MiR-125a-3p regulates glioma apoptosis and invasion by regulating Nrg1.
AB  - The current study was designed to examine the functional role and mechanism of
      miR-125a-3p in glioma development. Quantitative RT-PCR was used to evaluate miR
      125a-3p expression in 60 glioma cases of different malignant grades. Then, the
      clinic pathologic significance of miR-125a-3p expression was determined in
      combination with the prognosis of the patients. In addition, the effects and
      mechanisms of miR-125a-3p on the proliferation, apoptosis and invasion of glioma
      cells were further investigated. The results showed that the expression of miR
      125a-3p was decreased significantly in most malignant glioma samples relative to
      normal brain tissues and glioma tissues of low-malignant degree. Further kaplan
      meier survival analysis showed that the lower expression of miR-125a-3p was
      associated with a poor prognosis of GBM patients. Functional analysis showed that
      the reintroduction of miR-125a-3p into glioblastoma cell lines induces markedly
      the apoptosis and suppresses the proliferation and migration of glioblastoma
      cells in vitro and in vivo. Luciferase assay and Western blot analysis revealed
      that Nrg1 is a direct target of miR-125a-3p. Furthermore, an increased expression
      of Nrg1 could reverse the effects of overexpression of miR-125a-3p on the
      proliferation, apoptosis and migration of glioblastoma cells. These findings
      suggest that miR-125a-3p performed an important role in glioma development
      mediated by directly regulating the expression of Nrg1. This study also provides
      a potential target for diagnosis and treatment of malignant glioma. 

PMID- 25560391
TI  - Prenatal diesel exhaust exposure disrupts the DNA methylation profile in the
      brain of mouse offspring.
AB  - Prenatal diesel exhaust (DE) exposure is associated with detrimental health
      effects in offspring. Although previous reports suggest that DE exposure affects
      the brain of offspring in the developmental period, the molecular events
      associated with the health effects have largely remained unclear. We hypothesized
      that the DNA methylation state would be disrupted by prenatal DE exposure. In the
      present study, the authors examined the genome-wide DNA methylation state of the
      gene promoter and bioinformatically analyzed the obtained data to identify the
      molecular events related to disrupted DNA methylation. Pregnant C57BL/6J mice
      were exposed to DE (DEP; 0.1 mg/m<sup>3</sup>) in an inhalation chamber on
      gestational days 0-16. Brains were collected from 1-day-old and 21-day-old
      offspring. The genomewide DNA methylation state of the brain genome was analyzed
      by methylation-specific DNA immunoprecipitation and subsequent promoter tiling
      array analysis. The genes in which the DNA methylation level was affected by
      prenatal DE exposure were bioinformatically categorized using Gene Ontology (GO).
      Differentially methylated DNA regions were detected in all chromosomes in brains
      collected from both 1-day-old and 21-day-old offspring. Altered DNA methylation
      was observed independently of the presence of CpG island. Bioinformatic
      interpretation using GO terms showed that differentially methylated genes with
      CpG islands in their promoter were commonly enriched in neuronal differentiation
      and neurogenesis. The results suggest that prenatal DE exposure causes genome
      wide disruption of DNA methylation in the brain. Disrupted DNA methylation would
      disturb neuronal development in the developmental period and may be associated
      with health and disease in later life. 

PMID- 25560392
TI  - Involvement of reactive oxygen species in the cytotoxic effect of acid
      electrolyzed water.
AB  - Acid-electrolyzed water (AEW) is commonly used as a disinfectant in the
      agricultural and medical fields. Although several studies have been conducted to
      examine its toxicity in vitro and in vivo, the cytotoxic mechanism of AEW has
      never been verified. The purpose of the present study was to elucidate the
      underlying mechanism by which AEW exerts its in vitro cytotoxic effect. Mouse
      fibroblasts treated with AEW experienced dilution rate-dependent cytotoxic
      effects in the 100% confluent phase as well as in the mitotic phase. The levels
      of intracellular reactive oxygen species (ROS) increased significantly in fully
      confluent cells treated with undiluted and four times diluted AEW. In both of
      these treatments, cytotoxicity was also observed. It is thus concluded that the
      in vitro cytotoxicity of AEW is attributable to increased intracellular ROS.
      Additionally, the ROS responsible for these effects appears to be, at least in
      part, hydroxyl radical because the increase in intracellular ROS was attenuated
      by post-treatment with dimethyl sulfoxide, a hydroxyl radical scavenger, and with
      the antioxidant polyphenol, proanthocyanidin. 

PMID- 25560393
TI  - JNK implication in adipocyte-like cell death induced by chemotherapeutic drug
      cisplatin.
AB  - Recent evidence shows that tumor microenvironment containing heterogeneous cells
      may be involved in cancer initiation, growth and tumor cell response to
      anticancer therapy. Chemotherapy was designed to make toxic impact on malicious
      cells in organisms, however, the means to protect healthy cells against chemical
      toxicity are still unsuccessful. As known, the majority of tumor surrounding
      cells are cancer-associated adipocytes which influence cancer development,
      progression and treatment. Targeting the components of tumor microenvironment in
      combination with conventional cancer treatment may become an effective cancer
      therapy strategy. However, little is known about adipocyte death mechanisms
      during combined chemo- and targeted therapy. The importance of c-Jun
      NH<inf>2</inf>-terminal kinase (JNK) signaling in tumor development and treatment
      has been demonstrated using various in vitro and in vivo cancer models. The aim
      of this study was to ascertain adipocyte viability during simultaneous stress
      kinase JNK inhibition and exposure to one of the most commonly used anticancer
      drugs cis-diamminedichloroplatinum II (cisplatin). Our model involved adipocyte
      like cells (ADC) which were obtained during in vitro differentiation of adult
      rabbit muscle-derived stem cells. Cisplatin induced apoptotic cell death. During
      24-hr cisplatin treatment gradual, strong and prolonged increase of both JNK and
      its target protein c-Jun phosphorylation was found in ADC. Pre-treatment of cells
      with SP600125 decreased cisplatin-induced activation of c-Jun and promoted
      apoptosis. Upregulation of proapoptotic Bax and downregulation of antiapoptotic
      Bcl-2 proteins were found to be regulated in JNK-dependent manner. Thus, the
      results prove the antiapoptotic role of activated JNK in adipocyte-like cells
      treated with cisplatin. 

PMID- 25560394
TI  - Fluvoxamine by itself has potential to directly induce long QT syndrome at supra
      therapeutic concentrations.
AB  - Fluvoxamine is one of the typical selective serotonin-reuptake inhibitors. While
      its combined use with QT-prolonging drugs has been contraindicated because of the
      increase in plasma concentrations of such drugs, information is still limited
      whether fluvoxamine by itself may directly prolong the QT interval. We examined
      electropharmacological effects of fluvoxamine together with its pharmacokinetic
      profile by using the halothane-anesthetized dogs (n = 4). Fluvoxamine was
      intravenously administered in three escalating doses of 0.1, 1 and 10 mg/kg over
      10 min with a pause of 20 min between the doses. The low dose provided
      therapeutic plasma drug concentration, whereas the middle and high doses attained
      approximately 10 and 100 times of the therapeutic ones, respectively. Supra
      therapeutic concentration of fluvoxamine exerted the negative chronotropic,
      inotropic and hypotensive effects; and suppressed the atrioventricular nodal and
      intraventricular conductions, indicating inhibitory actions on Ca2+ and Na+
      channels, whereas it delayed the repolarization in a reverse use-dependent
      manner, reflecting characteristics of rapidly activating delayed rectifier K+
      current channel-blocking property. Fluvoxamine prolonged the terminal
      repolarization phase at 100 times higher concentration than the therapeutic,
      indicating its proarrhythmic potential. Thus, fluvoxamine by itself has potential
      to directly induce long QT syndrome at supra-therapeutic concentrations.

PMID- 25560395
TI  - Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague
      Dawley rats.
AB  - Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short
      chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the
      most common environmental endocrine disruptors, exhibits weak estrogen-like
      activity. In this study, we investigated whether oral administration of NP (at
      0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity,
      emotionality, and fear-motivated learning and memory in male and female Sprague
      Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of
      behavioral tests, including an appetite-motivated maze test (MAZE test) that was
      used to assess spatial learning and memory. In the MAZE test, the time required
      to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats
      administered 5 mg/kg NP was significantly longer than that for control animals of
      the corresponding sex. In other behavioral tests, no significant differences were
      observed between the control group and either of the NP-treated groups of male
      rats. In female rats, inner and ambulation values for animals administered 0.5
      mg/kg NP were significantly higher than those measured in control animals in open
      field test, while the latency in the group treated with 5 mg/kg NP was
      significantly shorter compared to the control group in step-through passive
      avoidance test. This study indicates that oral administration of a low-dose of NP
      slightly impairs spatial learning and memory performance in male and female rats,
      and alters emotionality and fear-motivated learning and memory in female rats
      only. 

PMID- 25560397
TI  - Palladium-catalyzed oxidative carbonylation of aromatic C-H bonds of N
      alkylanilines with CO and alcohols for the synthesis of o-aminobenzoates.
AB  - A Pd(II)-catalyzed C-H monocarbonylation of N-alkylanilines for the synthesis of
      o-aminobenzoates has been developed. Various aliphatic alcohols and phenol were
      tolerated in the reaction to afford the corresponding o-aminobenzoates in good
      yields under mild balloon pressure of CO. 

PMID- 25560396
TI  - MPTP-induced changes in hippocampal synaptic plasticity and memory are prevented
      by memantine through the BDNF-TrkB pathway.
AB  - BACKGROUND AND PURPOSE: Mild cognitive deficit in early Parkinson's disease (PD)
      has been widely studied. Here we have examined the effects of memantine in
      preventing memory deficit in experimental PD models and elucidated some of the
      underlying mechanisms. EXPERIMENTAL APPROACHES: I.p. injection of 1-methyl-4-
      phenyl-1,2,3,6-tetrahydro pyridine (MPTP) in C57BL/6 mice was used to produce
      models of PD. We used behavioural tasks to test memory. In vitro, we used slices
      of hippocampus, with electrophysiological, Western blotting, real time PCR, elisa
      and immunochemical techniques. KEY RESULTS: Following MPTP injection, long-term
      memory was impaired and these changes were prevented by pre-treatment with
      memantine. In hippocampal slices from MPTP treated mice, long-term potentiation
      (LTP) -induced by theta burst stimulation (10 bursts, 4 pulses) was decreased,
      while long-term depression (LTD) induced by low-frequency stimulation (1 Hz, 900
      pulses) was enhanced, compared with control values. A single dose of memantine
      (i.p., 10 mg.kg(-1) ) reversed the decreased LTP and the increased LTD in this PD
      model. Activity-dependent changes in tyrosine kinase receptor B (TrkB), ERK and
      brain-derived neurotrophic factor (BDNF) expression were decreased in slices from
      mice after MPTP treatment. These effects were reversed by pretreatment with
      memantine. Incubation of slices in vitro with 1-methyl-4-phenylpyridinium (MPP(+)
      ) decreased depolarization-induced expression of BDNF. This effect was prevented
      by pretreatment of slices with memantine or with calpain inhibitor III,
      suggesting the involvement of an overactivated calcium signalling pathway.
      CONCLUSIONS AND IMPLICATIONS: Memantine should be useful in preventing loss of
      memory and hippocampal synaptic plasticity in PD models.

PMID- 25560399
TI  - Spouses' involvement in older patients' fast-track programmes during total hip
      replacement using case management intervention. A study protocol of the SICAM
      trial.
AB  - AIM: To present the protocol of a two-group quasi-experimental study of spouses'
      involvement through case management (The SICAM-trial) in older patients' fast
      track programmes during total hip replacement. BACKGROUND: Patients in fast-track
      programmes are required to take an active part in their treatment and
      rehabilitation. Spouses of older patients can often provide valued practical and
      emotional support, reducing stress, pain and length of stay - yet they are seldom
      invited to participate in a supporting role. DESIGN: A two-group quasi
      experimental design with pre-test and repeated post-test measures (protocol
      approved in November 2012). METHODS: A total of 120 patients aged 65 years or
      older going through a fast-track programme for a total hip replacement and their
      spouses will be recruited from one Danish orthopaedic ward. We will initially
      include the control group for data collection and subsequently include the
      intervention group to avoid contamination of the control group. A case manager
      will be recruited to perform the case management intervention. Data will be
      collected from both groups at baseline, 2 weeks and 3 months after surgery.
      Outcome measures for patients include: functional status, nutrition, pain,
      depression and healthcare consumptions; and for spouses: caregiver satisfaction
      and difficulties and anxiety. CONCLUSION: The intervention will give further
      evidence on the need for relatives' participation in the patients' fast-track
      programmes and the results will contribute to education of the health
      professionals in their need to include relatives in fast-track programmes. The
      study was funded by the Novo Nordisk Foundation and the Regional Health
      Scientific Foundation of Sealand.

PMID- 25560401
TI  - Neonatal hemolysis and risk of bilirubin-induced neurologic dysfunction.
AB  - The pathologic phenotype of severe hyperbilirubinemia in the newborn infant is
      primarily due to excessive bilirubin production and/or impaired conjugation,
      resulting in an increased bilirubin load. This may, in turn, increase an infant's
      risk for the development of bilirubin-induced neurologic dysfunction (BIND). The
      highest-risk infants are those with increased bilirubin production rates due to
      hemolysis. Several immune and non-immune conditions have been found to cause
      severe hemolysis, and these are often exacerbated in those infants with perinatal
      sepsis and genetic predispositions. Therefore, identification of these infants,
      with novel technologies, is paramount in reducing the incidence of BIND and the
      long-term neurologic sequelae for these at-risk infants. 

PMID- 25560402
TI  - The decline of tracheotomy among otolaryngologists: a 14-year review.
AB  - OBJECTIVE: To determine the trend of number of tracheotomies performed by
      otolaryngologists. STUDY DESIGN: Case series with chart review. SETTING: Tertiary
      referral center in central Pennsylvania. SUBJECTS: All patients undergoing
      tracheotomy between 2000 and 2013. METHODS: Data were gathered from billing
      records and operative reports to determine the service performing the
      tracheotomy. In addition, the surgical technique and indication for surgery were
      recorded. Negative binomial regressions were conducted to examine the number of
      tracheotomies performed by each specialty as a function of year. RESULTS: In
      2000, 44% of tracheotomies were being performed by the otolaryngology service,
      compared with only 25% in 2013. This is a decline of 22% over time. Since 2000,
      general surgery steadily increased the number of tracheotomies performed in
      comparison to the steady decrease performed by otolaryngology. Since 2008,
      general surgeons have significantly increased the number of percutaneous
      tracheotomies they perform (76% per year). Over the same period, the number of
      tracheotomies performed by the cardiothoracic surgery service has steadily
      increased by 26% per year. Most of the tracheotomies performed by cardiothoracic
      surgery are percutaneous tracheotomies. CONCLUSION: This study illustrates that
      otolaryngologists at our institution are performing fewer tracheotomies over
      time. If this trend continues, the experience of our trainees may become diluted
      through reduction in surgical volume. While multi-institutional studies are
      warranted, this review provides a summary of data collected at a tertiary care
      institution, which may reflect national trends.

PMID- 25560400
TI  - HES5 silencing is an early and recurrent change in prostate tumourigenesis.
AB  - Prostate cancer is the most common cancer in men, resulting in over 10 000
      deaths/year in the UK. Sequencing and copy number analysis of primary tumours has
      revealed heterogeneity within tumours and an absence of recurrent founder
      mutations, consistent with non-genetic disease initiating events. Using
      methylation profiling in a series of multi-focal prostate tumours, we identify
      promoter methylation of the transcription factor HES5 as an early event in
      prostate tumourigenesis. We confirm that this epigenetic alteration occurs in 86
      97% of cases in two independent prostate cancer cohorts (n=49 and n=39 tumour
      normal pairs). Treatment of prostate cancer cells with the demethylating agent 5
      aza-2'-deoxycytidine increased HES5 expression and downregulated its
      transcriptional target HES6, consistent with functional silencing of the HES5
      gene in prostate cancer. Finally, we identify and test a transcriptional module
      involving the AR, ERG, HES1 and HES6 and propose a model for the impact of HES5
      silencing on tumourigenesis as a starting point for future functional studies. 

PMID- 25560403
TI  - Nystagmus discordance with 2-dimensional videonystagmography in posterior
      semicircular canal benign paroxysmal positional vertigo.
AB  - OBJECTIVE: The Dix-Hallpike test is a standard component of the
      videonystagmography test battery and can diagnose posterior semicircular canal
      benign paroxysmal positional vertigo. The purpose of this study is to determine
      the prevalence of discordant, equivocal, and concordant nystagmus tracings in
      active posterior semicircular canal benign paroxysmal positional vertigo when
      compared directly with the eye video. STUDY DESIGN: Case series with chart review
      of patients diagnosed with posterior semicircular canal benign paroxysmal
      positional vertigo by 2-dimensional videonystagmography from August 1, 2007, to
      August 1, 2012. SETTING: A tertiary vestibular test laboratory. SUBJECTS AND
      METHODS: Ninety-six adults (4 had bilateral involvement) with posterior
      semicircular canal benign paroxysmal positional vertigo were included. A total of
      100 videos with accompanying videonystagmography tracings were reviewed to
      determine nystagmus trajectory as well as globe position. Descriptive statistics
      were used to describe prevalence. Fisher exact test was used to compare
      proportions. RESULTS: Sixty-two percent of cases involved benign paroxysmal
      positional vertigo of the right posterior semicircular canal, while 38% involved
      the left posterior semicircular canal. The prevalence of discordant, equivocal,
      and concordant tracings was 65% (65/100), 29% (29/100), and 6% (6/100). All
      tracing errors involved the horizontal channel. There was no association between
      tracing accuracy and the ear of involvement or globe position (P > .05).
      CONCLUSIONS: Two-dimensional videonystagmography tracings are not reliable for
      identifying nystagmus trajectory in posterior semicircular canal benign
      paroxysmal positional vertigo.

PMID- 25560404
TI  - Lack of association between human herpesvirus and vestibular schwannoma: analysis
      of 121 cases.
AB  - OBJECTIVE: To assess for the presence of human herpesvirus (HHV) using
      immunohistochemical and polymerase chain reaction (PCR) assay in surgically
      excised vestibular schwannoma (VS) samples. STUDY DESIGN: Cross-sectional study.
      SETTING: A retrospective laboratory-based study of tumors from patients with
      vestibular schwannoma. SUBJECTS AND METHODS: Tissue microarrays (TMAs)
      representing sporadic and NF2-associated VS from 121 patients, as well as
      appropriate positive and negative controls, were studied. TMA sections were
      immunostained using antibodies directed against HHV-1, HHV-2, HHV-3, HHV-4, HHV
      5, and HHV-8. PCR was used for the detection of all 8 known human herpesviruses.
      RESULTS: There was no detectable HHV (HHV-1, HHV-2, HHV-3, HHV-4, HHV-5, HHV-8)
      by immunohistochemistry in any of the 121 cases of sporadic and NF2 cases
      analyzed. These data were further validated by DNA sequence analyses using PCR in
      a subset of the VS samples, all of which were found to be negative for all HHV.
      CONCLUSIONS: The data offer no support for an association between HHV and the
      development of sporadic or NF2-associated VS in humans.

PMID- 25560406
TI  - Pharyngeal wall floppiness: a novel technique to detect upper airway
      collapsibility in patients with OSAS.
AB  - OBJECTIVE: To measure pharyngeal wall floppiness (PWF) under different pressures,
      a novel method and technique were introduced in the present study. STUDY DESIGN:
      A prospective clinical study. SUBJECTS AND METHODS: Forty-seven healthy subjects
      (32 male; mean age, 37.9 years) and 49 patients with obstructive sleep apnea
      syndrome (OSAS) (46 male; mean age, 41.45 years) were recruited. The pharyngeal
      cavity volume was measured by acoustic reflection under positive (10 cm H2O) and
      negative (-10 cm H2O) pressures. The pharyngeal cavity volume was detected from
      the segment of 10 to 20 cm from the incisor. Moreover, PWF was calculated from
      the difference of pharyngeal cavity volumes under positive and negative pressures
      divided by the sum of the volumes under positive and negative pressures. The
      measurements were conducted on a group of 7 subjects weekly over 3 consecutive
      weeks to evaluate test-retest variability. RESULTS: The mean PWF was 0.19 +/-
      0.11 in healthy subjects and 0.24 +/- 0.07 in the OSAS group, with a significant
      difference (P < .01). There was moderate positive correlation between PWF and age
      or body mass index in healthy subjects. In the 7 subjects, the mean measured
      interclass correlation coefficient was 0.9 (P < .05) in 3 consecutive weekly
      measurements. CONCLUSION: The OSAS population had greater PWF compared to healthy
      subjects. The age dependency of PWF in healthy subjects implied which might play
      important roles in the development of OSAS. This noninvasive and reproducible
      technique might be a useful tool in OSAS clinical applications.

PMID- 25560405
TI  - Impact of nonaspirin nonsteroidal anti-inflammatory agents and acetaminophen on
      sensorineural hearing loss: a systematic review.
AB  - OBJECTIVE: To perform a systematic review evaluating the association between
      sensorineural hearing loss and (1) nonsteroidal anti-inflammatory drugs (NSAIDs)
      as a class, (2) NSAIDs available over the counter, (3) NSAIDs in short
      intravenous courses, (4) prescription NSAIDs utilized by patients without
      systemic inflammatory conditions, (5) prescription NSAIDs in patients with
      arthritides, and (6) acetaminophen with and without concomitant narcotic usage.
      DATA SOURCES: Computerized searches of PubMed, EMBASE, and the Cochrane Library
      were updated through May 2014, along with manual searches and inquiries to topic
      experts. REVIEW METHODS: The systematic review was performed according to an a
      priori protocol. Data extraction was performed by 2 independent investigators,
      and it focused on relevant audiologic measurements, methodological elements
      related to risk of bias, and potential confounders. RESULTS: The 23 criterion
      meeting studies included a total of 92,532 participants, with mixed results.
      Sulindac was the only specific agent to have been studied with formal audiometry
      in a randomized double-blind placebo-controlled trial in which hearing was the
      reported primary outcome: Although an effect was seen in the unadjusted analysis
      (pure tone threshold>15 dB, 9.3% vs 2.9%; relative risk [RR], 3.2; confidence
      interval [CI], 1.09-9.55; P=.02), the effect dissipated in the adjusted analysis
      (P=.09). There was a significant effect on self-reported hearing loss from NSAIDs
      as a class (RR, 1.21; CI, 1.11-1.33), ibuprofen (RR, 1.13; CI, 1.06-1.19), and
      acetaminophen (RR, 1.21; CI, 1.11-1.33), but no formal audiometric data confirm
      or refute this suggested effect. Audiometry has demonstrated profound loss in
      some instances of acetaminophen-narcotic combination ingestions. CONCLUSIONS:
      Data are varied regarding the impact of NSAIDs and acetaminophen on population
      hearing health.

PMID- 25560407
TI  - Treatment outcomes of temporal bone osteoradionecrosis.
AB  - OBJECTIVE: To investigate the clinical relevance of the classification systems
      used for temporal bone osteoradionecrosis (ORN) and to define a treatment
      protocol for temporal bone ORN. STUDY DESIGN: Retrospective case series. SETTING:
      Amsterdam, department of otorhinolaryngology and head and neck surgery. SUBJECTS
      AND METHODS: Classification of temporal bone ORN was performed through use of
      clinical data and radiologic imaging. Outcomes of conservative and surgical
      treatment were investigated and compared for different grades of ORN. RESULTS: Of
      the 49 ears included in this study, 35 were primarily treated conservatively. At
      start of conservative treatment, 23 were classified as a localized and 8 as a
      diffuse form of ORN; 4 could not be classified. There was a significant
      difference in clinical outcome between the localized and diffuse forms of ORN
      (chi(2) = 5.862, P = .015), and mastoid air cell destruction on preoperative
      computed tomography scan was found to be a significant predictor for a negative
      outcome of conservative treatment (chi(2) = 4.34, P = .037). Fourteen ears with
      diffuse ORN were primarily treated surgically, and 11 were secondarily treated
      surgically following a period of conservative treatment. Twenty-two patients were
      treated with subtotal petrosectomy, of which 20 were cured. Three patients were
      treated with canal wall down mastoidectomy, and 2 had recurrence of disease.
      CONCLUSION: Ramsden's classification system is clinically relevant in predicting
      conservative treatment outcomes. Mastoid air cell destruction on computed
      tomography differentiates between the localized and diffuse forms of ORN. Given
      our results and experience with treating temporal bone ORN, we propose a
      treatment protocol.

PMID- 25560398
TI  - CRF07_BC Strain Dominates the HIV-1 Epidemic in Injection Drug Users in Liangshan
      Prefecture of Sichuan, China.
AB  - The Liangshan prefecture in Sichuan province is an area in China severely
      affected by the HIV epidemic, with intravenous drug use (IDU) as the main risk
      factor. No reports on HIV subtypes prevalent in IDUs in Liangshan prefecture
      could be found. In this study, we have characterized the genotypes of HIV-1 in
      the IDU population in Liangshan prefecture and further determined the
      phylogenetic relationship of the CRF07_BC strains to HIV-1 sequences from the
      other regions of China, including Xinjiang and Yunnan provinces, to explore the
      pattern and possible diffusion pathway of HIV-1 in these regions. HIV-1
      seropositive drug-naive IDUs identified in Liangshan prefecture, Sichuan province
      were enrolled in 2009. Full-length gag and pol genes were amplified by reverse
      transcription and nested PCR and then sequenced. All of the sequences were
      subtyped. Phylogenetic trees were constructed using the neighbor-joining and
      maximum likelihood methods. Divergence times were estimated using a Bayesian
      molecular clock approach. CRF07_BC was found to be the predominant strain in IDUs
      in Liangshan prefecture (95.5%). The CRF07_BC strains from Liangshan prefecture
      were found to be intermixed with those from Yunnan province in phylogenetic
      trees. The CRF07_BC sequences from Xinjiang province can be grouped into several
      clusters, suggesting that the expansion of the CRF07_BC epidemic in Xinjiang
      province was the result of a local epidemic driven by multiple independent
      introductions in the late 1990s. Only low-level drug-resistant viruses were found
      in the IDU population. CRF07_BC strains from Liangshan prefecture were more
      similar to those from Yunnan province than those from Xinjiang province. This
      finding will contribute to our understanding of the distribution, the evolution,
      and the potential source of CRF07_BC founder strains, and will also provide
      useful information for the development of strategies to prevent transmission. 

PMID- 25560409
TI  - The human fetal placenta promotes tolerance against the semiallogeneic fetus by
      inducing regulatory T cells and homeostatic M2 macrophages.
AB  - A successful pregnancy requires that the maternal immune system is instructed to
      a state of tolerance to avoid rejection of the semiallogeneic fetal-placental
      unit. Although increasing evidence supports that decidual (uterine) macrophages
      and regulatory T cells (Tregs) are key regulators of fetal tolerance, it is not
      known how these tolerogenic leukocytes are induced. In this article, we show that
      the human fetal placenta itself, mainly through trophoblast cells, is able to
      induce homeostatic M2 macrophages and Tregs. Placental-derived M-CSF and IL-10
      induced macrophages that shared the CD14(+)CD163(+)CD206(+)CD209(+) phenotype of
      decidual macrophages and produced IL-10 and CCL18 but not IL-12 or IL-23.
      Placental tissue also induced the expansion of CD25(high)CD127(low)Foxp3(+) Tregs
      in parallel with increased IL-10 production, whereas production of IFN-gamma
      (Th1), IL-13 (Th2), and IL-17 (Th17) was not induced. Tregs expressed the
      suppressive markers CTLA-4 and CD39, were functionally suppressive, and were
      induced, in part, by IL-10, TGF-beta, and TRAIL. Placental-derived factors also
      limited excessive Th cell activation, as shown by decreased HLA-DR expression and
      reduced secretion of Th1-, Th2-, and Th17-associated cytokines. Thus, our data
      indicate that the fetal placenta has a central role in promoting the homeostatic
      environment necessary for successful pregnancy. These findings have implications
      for immune-mediated pregnancy complications, as well as for our general
      understanding of tissue-induced tolerance. 

PMID- 25560408
TI  - Alkylating agent melphalan augments the efficacy of adoptive immunotherapy using
      tumor-specific CD4+ T cells.
AB  - In recent years, the immune-potentiating effects of some widely used
      chemotherapeutic agents have been increasingly appreciated. This provides a
      rationale for combining conventional chemotherapy with immunotherapy strategies
      to achieve durable therapeutic benefits. Previous studies have implicated the
      immunomodulatory effects of melphalan, an alkylating agent commonly used to treat
      multiple myeloma, but the underlying mechanisms remain obscure. In the present
      study, we investigated the impact of melphalan on endogenous immune cells as well
      as adoptively transferred tumor-specific CD4(+) T cells in tumor-bearing mice. We
      showed that melphalan treatment resulted in a rapid burst of inflammatory
      cytokines and chemokines during the cellular recovery phase after melphalan
      induced myelodepletion and leukodepletion. After melphalan treatment, tumor cells
      exhibited characteristics of immunogenic cell death, including membrane
      translocation of the endoplasmic reticulum-resident calreticulin and
      extracellular release of high-mobility group box 1. Additionally, there was
      enhanced tumor Ag uptake by dendritic cells in the tumor-draining lymph node.
      Consistent with these immunomodulatory effects, melphalan treatment of tumor
      bearing mice led to the activation of the endogenous CD8(+) T cells and, more
      importantly, effectively drove the clonal expansion and effector differentiation
      of adoptively transferred tumor-specific CD4(+) T cells. Notably, the combination
      of melphalan and CD4(+) T cell adoptive cell therapy was more efficacious than
      either treatment alone in prolonging the survival of mice with advanced B cell
      lymphomas or colorectal tumors. These findings provide mechanistic insights into
      melphalan's immunostimulatory effects and demonstrate the therapeutic potential
      of combining melphalan with adoptive cell therapy utilizing antitumor CD4(+) T
      cells. 

PMID- 25560410
TI  - Bortezomib reduces pre-existing antibodies to recombinant immunotoxins in mice.
AB  - Recombinant immunotoxin (RIT) therapy is limited in patients by neutralizing Ab
      responses. Ninety percent of patients with normal immune systems make
      neutralizing Abs after one cycle of RIT, preventing repeated dosing. Furthermore,
      some patients have pre-existing Abs from environmental exposure to Pseudomonas
      exotoxin, the component of the RIT that elicits the neutralizing Ab response.
      Bortezomib is an U.S. Food and Drug Administration-approved proteasome inhibitor
      that selectively targets and kills plasma cells that are necessary for the
      neutralizing Ab response. We hypothesized that bortezomib may abrogate
      neutralizing Ab levels, making dosing of RIT possible in mice already immune to
      RIT. We immunized BALB/c mice with multiple doses of SS1P, a RIT whose Ab portion
      targets mesothelin. Mice with elevated Ab levels were separated into groups to
      receive saline, bortezomib, the pentostatin/cyclophosphamide (PC) regimen, or the
      bortezomib/PC (BPC) combination regimen. Four weeks after finishing therapy,
      plasma Ab levels were assayed, and bone marrow was harvested. The bortezomib and
      PC regimens significantly reduced Ab levels, and we observed fewer plasma cells
      in the bone marrow of bortezomib-treated mice but not in PC-treated mice. The BPC
      combination regimen almost completely eliminated Abs and further reduced plasma
      cells in the bone marrow. This regimen is more effective than individual regimens
      and may reduce Ab levels in patients with pre-existing neutralizing Abs to
      Pseudomonas exotoxin, allowing RIT treatment. 

PMID- 25560411
TI  - E3 Ubiquitin Ligase Cbl-b Regulates Thymic-Derived CD4+CD25+ Regulatory T Cell
      Development by Targeting Foxp3 for Ubiquitination.
AB  - CD28 costimulation is essential for the development of thymic-derived
      CD4(+)CD25(+)Foxp3(+) regulatory T cells ("tTregs"). E3 ubiquitin ligase Cbl-b
      has been shown to regulate CD28 dependence of T cell activation. In this paper,
      we report that the loss of Cbl-b partially but significantly rescues the
      defective development of tTregs in Cd28(-/-) mice. This partial rescue is
      independent of IL-2. Mechanistically, Cbl-b binds to Foxp3 upon TCR stimulation
      and, together with Stub1, targets Foxp3 for ubiquitination and subsequently
      degradation in the proteasome. As Cbl-b self-ubiquitination and proteasomal
      degradation is impaired in Cd28(-/-) T cells, the defective development of tTregs
      in Cd28(-/-) mice may in part be due to increased Foxp3 ubiquitination and
      degradation targeted by Stub1 and Cbl-b. Treating Cd28(-/-) mice with a
      proteasome inhibitor completely rescues defective tTreg development in these
      mice. Therefore, Cbl-b, together with Stub1, ubiquitinate Foxp3, and regulate
      tTreg development. 

PMID- 25560414
TI  - Parameters predicting lymph node metastasis in patients with superficial
      esophageal squamous cell carcinoma.

PMID- 25560413
TI  - Immunohistochemical pitfalls in the diagnosis of hepatocellular adenomas and
      focal nodular hyperplasia: accurate understanding of diverse staining patterns is
      essential for diagnosis and risk assessment.

PMID- 25560415
TI  - Influence of collection time on hematologic and immune markers in the American
      alligator (Alligator mississippiensis).
AB  - Crocodilians are important keystone species and indicators of environmental
      health. Much remains unknown, however regarding utility of field-collected
      crocodilian blood samples for ecologic assessments. Field sampling sites are also
      often distant to analysis centers, necessitating development of new techniques
      and panels of assays that will yield environmentally relevant data. Stability and
      viability of hematological and immunological indices have been of particular
      interest for linking ecosystem health to biomarkers in resident species. In this
      study, we investigated the effect of time at analysis post-blood sampling at 4
      and 24 hr on a panel of potential biomarkers in alligator blood. Our results
      suggest alligator blood samples can be reliably evaluated for both hematologic
      and immunologic profile 24 hr after sampling. 

PMID- 25560416
TI  - Effects of divalent cations, EDTA and chitosan on the uptake and
      photoinactivation of Escherichia coli mediated by cationic and anionic
      porphyrins.
AB  - The effect of divalent cations, EDTA and chitosan (CS) on the uptake and
      photoinactivation of Escherichia coli produced by 5,10,15,20-tetrakis(4-N,N,N
      trimethylammoniumphenyl)porphyrin (TMAP(4+)), 5,10-di(4-methylphenyl)-15,20-di(4
      N,N,N-trimethylammoniumphenyl)porphyrin (MPAP(2+)) and 5,10,15,20-tetra(4
      sulphonatophenyl)porphyrin (TPPS(4-)) were examined under different conditions.
      These porphyrins were rapidly bound to E. coli cells (<2.5min) and the uptake of
      photosensitizers was not dependent on incubation temperature, reaching values of
      0.61, 0.18 and 0.08nmol/10(8) cells for TMAP(4+), MPAP(2+) and TPPS(4-),
      respectively. The addition of Ca(2+) or Mg(2+) to the cultures enhanced the
      uptake of MPAP(2+) and TPPS(4-) by cells. In contrast, the amount of TMAP(4+)
      bound to cells was decreased. The presence of EDTA produced an increase in the
      uptake of porphyrins by cells, while CS mainly enhanced the amount of TPPS(4-)
      bound to E. coli. The photoinactivation of E. coli cells mediated by TMAP(4+) was
      highly effective even at low concentration (1MUM) and short irradiation period
      (5min). However, a reduction in the phototoxicity was found for TMAP(4+) in
      presence of Ca(2+) and Mg(2+). In contrast, the phototoxic activity mediated by
      MPAP(2+) and TPPS(4-) was increased. Addition of EDTA did not show effect on the
      photoinactivation induced by cationic porphyrins, while a small enhance was found
      for TPPS(4-). Moreover, inactivation of E. coli cells was achieved in the
      presence CS. This cationic polymer was antimicrobial by itself in the dark. Using
      a slightly toxic CS concentration, the phototoxic activity induced by TMAP(4+)
      was diminished. This effect was mainly observed at lower concentration of
      TMAP(4+) (0.5-1MUM). In contrast, an increase in E. coli photoinactivation was
      obtained for MPAP(2+) and TPPS(4-) in presence of CS. Thus, this natural
      polymeric destabilizer agent mainly benefited the photoinactivation mediated by
      TPPS(4-).

PMID- 25560417
TI  - Laser-induced autofluorescence spectroscopy: can it be of importance in detection
      of bladder lesions?
AB  - BACKGROUND: Non-muscle invasive bladder cancer can be missed during white light
      endoscopy in up to 50% of cases. We aimed to test whether or not we could find a
      difference between benign and cancerous tissue wavelengths using laser induced
      autofluorescence spectroscopy can increase cancer detection. MATERIALS AND
      METHODS: We analysed 67 tissue samples using spectral analysis. The WavSTAT
      (Spectra Science) optical biopsy device was used to record fluorescence spectra
      from biopsied tissue enabling calculation of an AUC for each spectrum, a measure
      of the mean spectral wavelength (lambda- (nm)) and a dimensionless fluorescence
      ratio. Mann-Whitney test was used to compare the two groups. RESULTS: We found
      that 49.3% (33/67) of the tissue was benign, 44.8% (30/67) was CIS/cancerous
      tissue, and the remaining 4/67 samples were atypia (2) and dysplasia (2). The
      median AUC for the benign tissue was 19.53 (interquartile range [IQR]: 5.35
      30.39) and that for CIS/cancerous tissue was 7.05 (IQR: 2.89-14.24) (P=0.002).
      The median wavelengths for the benign tissue and malignant tissue were 502.4nm
      (IQR: 500.3-504.3nm) and 505.2nm (IQR: 502.1-513.2nm), respectively (P=0.003).
      The median fluorescence ratio was 0.080 (IQR: 0.070-0.088) for benign tissue and
      0.096 (IQR: 0.079-0.221) for CIS/cancerous tissue (P=0.002). CONCLUSIONS: We
      found statistical differences between the median AUC calculations and median
      wavelengths for the benign and cancerous tissue. We also found a statistical
      difference between the fluorescence ratios between the two tissue types. There
      seems to be a role for optical spectroscopy in verifying bladder lesions.

PMID- 25560418
TI  - In vitro photodynamic inactivation of Candida albicans by phenothiazine dye (new
      methylene blue) and Indocyanine green (EmunDo(r)).
AB  - BACKGROUND: The application of a new generation of photosensitizers to increase
      the efficacy of antifungal photodynamic therapy (aPDT) is an important aspect of
      PDT. Thus, this in vitro study is aimed to evaluate the antifungal efficacy of
      the photo-elimination of Candida albicans with photothermal and antifungal
      photodynamic therapy. METHOD AND MATERIAL: aPDT with new methylene blue and
      photothermal therapy with EmunDo(r) were applied to a fungal suspension, which
      was then subcultured in Sabouraud dextrose agar (SDA). The C. albicans colonies
      were counted and are expressed as colony-forming unit per milliliter (CFU/ml).
      RESULTS: aPDT with either EmunDo(r) or new methylene blue (NMB) considerably
      diminished the viability of inoculated C. albicans (P<0.001) by log reduction of
      1.9 and 3.37, respectively, compared with the control group respectively,
      compared with the control group. The antifungal potency or dark toxicity of the
      two photosensitizers alone did not significantly differ (P=0.70). The same trend
      was observed for the light sources (lambda: 810nm vs. lambda: 630nm), which also
      did not significantly differ (P=0.78). CONCLUSION: The photo-elimination of C.
      albicans with either new methylene blue or EmunDo(r) as a photosensitizer can
      reduce the viability of fungal cells. Although the result of this study is
      encouraging, further investigations are warranted to determine clear protocols
      for the reliable and safe application of this method in clinical practice.

PMID- 25560419
TI  - Diffuse choroidal hemangioma associated with exudative retinal detachment in a
      Sturge-Weber syndrome case: photodynamic therapy and intravitreous bevacizumab.
AB  - We report the case of a young female patient with a diffuse choroidal hemangioma
      (DCH) and glaucoma as part of Sturge-Weber syndrome (SWS) and symptomatic retinal
      detachment that was treated successfully with photodynamic therapy (PDT) and
      intravitreal bevacizumab (IVB). The patient was treated with a single session of
      PDT, a 689-nm laser was used to deliver 50J/cm(2) with a maximum spot size of
      6400MUm, for 166s. IVB was administered 3 days later. The exudative retinal
      detachment (ERD), macular edema and visual acuity improved one week after
      treatment. The patient was followed for 18 months with no recurrence of ERD, and
      her visual acuity was preserved. PDT followed by IVB may be an effective
      treatment option for visual deterioration due to ERD in patients with DCHs, as
      are found in SWS.

PMID- 25560420
TI  - Hybrid histidine kinases in pathogenic fungi.
AB  - Histidine kinases (HK) sense and transduce via phosphorylation events many intra-
      and extracellular signals in bacteria, archaea, slime moulds and plants. HK are
      also widespread in the fungal kingdom, but their precise roles in the regulation
      of physiological processes remain largely obscure. Expanding genomic resources
      have recently given the opportunity to identify uncharacterised HK family members
      in yeasts and moulds and now allow proposing a complex classification of
      Basidiomycota, Ascomycota and lower fungi HK. A growing number of genetic
      approaches have progressively provided new insight into the role of several
      groups of HK in prominent fungal pathogens. In particular, a series of studies
      have revealed that members of group III HK, which occur in the highest number of
      fungal species and contain a unique N-terminus region consisting of multiple HAMP
      domain repeats, regulate morphogenesis and virulence in various human, plant and
      insect pathogenic fungi. This research field is further supported by recent shape
      function studies providing clear correlation between structural properties and
      signalling states in group III HK. Since HK are absent in mammals, these
      represent interesting fungal target for the discovery of new antifungal drugs. 

PMID- 25560421
TI  - Hemofiltration is not associated with increased mortality in children receiving
      extracorporeal membrane oxygenation.
AB  - OBJECTIVES: To investigate whether the use of continuous renal replacement
      therapy is independently associated with increased in-hospital mortality in
      children on extracorporeal membrane oxygenation. DESIGN: Retrospective, 1:1
      propensity-matched cohort study. SETTING: Tertiary PICU. PATIENTS: Eighty-six
      children on extracorporeal membrane oxygenation, 43 of whom also received
      hemofiltration. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics,
      pre-extracorporeal membrane oxygenation hemodynamic data, fluid status, and
      biochemistry tests were collected, as well as duration of extracorporeal membrane
      oxygenation, blood product use, complications, and mortality. Forty-three
      children receiving extracorporeal membrane oxygenation and continuous renal
      replacement therapy were matched to a cohort of 43 children on extracorporeal
      membrane oxygenation not receiving continuous renal replacement therapy. The main
      indication for hemofiltration was fluid overload in 29 patients (67.4%), renal
      failure in nine patients (20.9%), and electrolyte abnormalities in five patients
      (11.6%). The median duration of hemofiltration was 108 hours (47-209 hr).
      Patients receiving hemofiltration had a longer duration of extracorporeal
      membrane oxygenation (127 hr [94-302 hr] vs 121 hr [67-182 hr]; p = 0.05) and
      received more platelet transfusions (0.91 mL/kg/hr [0.43-1.58 mL/kg/hr] vs 0.63
      mL/kg/hr [0.30-0.79 mL/kg/hr]; p = 0.01). There were otherwise no differences in
      mechanical or patient-related complications between both groups. There was no
      difference in the proportion of patients who were successfully decannulated
      (81.4% vs 74.4%; p = 0.44), survived to ICU discharge (65.1% vs 55.8%; p = 0.38),
      or survived to hospital discharge (62.8% vs 48.8%; p = 0.19) in the controls
      versus the hemofiltration group. CONCLUSIONS: In-hospital mortality was similar
      between children on extracorporeal membrane oxygenation with and without
      hemofiltration although hemofiltration appeared to be associated with a slight
      increase in the duration of extracorporeal membrane oxygenation and more liberal
      platelet transfusions.

PMID- 25560422
TI  - Low thiamine levels in children with type 1 diabetes and diabetic ketoacidosis: a
      pilot study.
AB  - OBJECTIVE: Thiamine deficiency has been documented in adults with diabetes and in
      a single report of reversible encephalopathy in a child with diabetic
      ketoacidosis. In children who present with severe diabetic ketoacidosis, one of
      the most serious complications is cerebral edema of which the primary symptom may
      be encephalopathy. Thiamine deficiency in other disease states has been clearly
      linked with acute encephalopathy, but there are no data on thiamine status in
      children with diabetic ketoacidosis. This study describes the prevalence of
      thiamine deficiency in children with type 1 diabetes mellitus who present with
      diabetic ketoacidosis and are admitted to the ICU. DESIGN: A prospective
      observational pilot study. SETTING: PICU in a tertiary care children's hospital.
      PATIENTS: Children 2-18 years admitted to the ICU for treatment of diabetic
      ketoacidosis. INTERVENTIONS: Treatment of diabetic ketoacidosis. MEASUREMENTS AND
      MAIN RESULTS: Twenty-two patients were enrolled. The mean age was 13.7 +/- 3.6
      years. Five of 21 patients (23.8%) had thiamine deficiency prior to insulin
      administration. After 8 hours of insulin therapy, seven of 20 patients (35%) had
      thiamine deficiency, and four of these seven patients also had thiamine
      deficiency at presentation. Sixty-eight percent of patients had a decrease in
      thiamine levels after 8 hours of insulin therapy, with a mean fall of 20 +/- 31.4
      nmol/L. CONCLUSIONS: Thiamine deficiency is common in children with diabetic
      ketoacidosis, and this deficiency may be worsened by treatment. When metabolic
      acidosis persists despite appropriate treatment of diabetic ketoacidosis, other
      factors such as thiamine deficiency should be considered.

PMID- 25560423
TI  - Comparison between noninvasive mechanical ventilation and standard oxygen therapy
      in children up to 3 years old with respiratory failure after extubation: a pilot
      prospective randomized clinical study.
AB  - OBJECTIVES: The effectiveness of noninvasive positive-pressure ventilation in
      preventing reintubation due to respiratory failure in children remains uncertain.
      A pilot study was designed to evaluate the frequency of extubation failure,
      develop a randomization approach, and analyze the feasibility of a powered
      randomized trial to compare noninvasive positive-pressure ventilation and
      standard oxygen therapy post extubation for preventing reintubation within 48
      hours in children with respiratory failure. DESIGN: Prospective pilot study.
      SETTING: PICU at a university-affiliated hospital. PATIENTS: Children aged
      between 28 days and 3 years undergoing invasive mechanical ventilation for
      greater than or equal to 48 hours with respiratory failure after programmed
      extubation. INTERVENTIONS: Patients were prospectively enrolled and randomly
      assigned into noninvasive positive-pressure ventilation group and inhaled oxygen
      group after programmed extubation from May 2012 to May 2013. MEASUREMENTS AND
      MAIN RESULTS: Length of stay in PICU and hospital, oxygenation index, blood gas
      before and after tracheal extubation, failure and reason for tracheal extubation,
      complications, mechanical ventilation variables before tracheal extubation,
      arterial blood gas, and respiratory and heart rates before and 1 hour after
      tracheal extubation were analyzed. One hundred eight patients were included
      (noninvasive positive-pressure ventilation group, n = 55 and inhaled oxygen
      group, n = 53), with 66 exclusions. Groups did not significantly differ for
      gender, age, disease severity, Pediatric Risk of Mortality at admission, tracheal
      intubation, and mechanical ventilation indications. There was no statistically
      significant difference in reintubation rate (noninvasive positive-pressure
      ventilation group, 9.1%; inhaled oxygen group, 11.3%; p > 0.05) and length of
      stay (days) in PICU (noninvasive positive-pressure ventilation group, 3 [1-16];
      inhaled oxygen group, 2 [1-25]; p > 0.05) or hospital (noninvasive positive
      pressure ventilation group, 19 [7-141]; inhaled oxygen group, 17 [8-80]).
      CONCLUSIONS: The study indicates that a larger randomized trial comparing
      noninvasive positive-pressure ventilation and standard oxygen therapy in children
      with respiratory failure is feasible, providing a basis for a future trial in
      this setting. No differences were seen between groups. The number of excluded
      patients was high.

PMID- 25560424
TI  - Bumetanide continuous infusions in critically ill pediatric patients.
AB  - OBJECTIVE: Limited data exist for the use of bumetanide continuous infusions in
      children. The purpose of this study was to evaluate the use of bumetanide
      continuous infusions in critically ill pediatric patients. DESIGN: This study was
      an institutional review board approved, single-center, retrospective chart review
      of 95 patients. Dosing practices were described by rate (MUg/kg/hr), duration
      (days), and previous diuretic use. Efficacy, determined by ability to achieve
      negative fluid balance and time to reach negative fluid balance, was assessed at
      12, 24, and 48 hours. Safety was evaluated based on prevalence of adverse drug
      reactions. Adverse drug reactions were predefined as serum potassium
      concentration less than 3 mEq/L, serum chloride concentration less than 90 mEq/L,
      serum carbon dioxide concentration greater than 35 mEq/L, and serum creatinine
      increased greater than 1.5 times baseline and above patient-specific normal
      range. SETTING: Le Bonheur Children's Hospital, Memphis, TN. PATIENTS: Critically
      ill patients who are 18 years old or younger and received bumetanide continuous
      infusions. A total of 95 patients were included. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The mean dose of bumetanide was 5.7 +/- 2.2
      MUg/kg/hr (1-10 MUg/kg/hr) with a median duration of 3.3 days (0.3-18.5). The
      total percentage of patients achieving negative fluid balance by 48 hours was 76%
      with 54% of patients reaching negative fluid balance within 12 hours.
      CONCLUSIONS: This study showed that a bumetanide dose of 5.7 MUg/kg/hr was
      effective in achieving negative fluid balance in the majority of critically ill
      pediatric patients. Additionally, bumetanide appears to be a safe loop diuretic
      for use as a continuous infusion at the doses described in critically ill
      pediatric patients.

PMID- 25560425
TI  - Evaluation of the relationship between plasma transfusion and nosocomial
      infection after cardiac surgery in children younger than 1 year.
AB  - OBJECTIVES: Recent data have suggested a link between plasma transfusion and the
      development of nosocomial infections in critically ill children. However, to our
      knowledge, no study has specifically focused on this association among children
      undergoing cardiac surgery. Thus, the main objective of this study was to analyze
      the relationship between plasma transfusion after cardiac surgery and the risk of
      nosocomial infections, including bloodstream infections, mediastinitis, and
      ventilator-associated pneumonia, in children younger than 1 year. DESIGN:
      Observational single-center study. SETTING: A 12-bed tertiary PICU in a
      university hospital in France. PATIENTS: Children less than 1 year admitted after
      cardiac surgery under cardiopulmonary bypass between November 2007 and December
      2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 233 children
      were analyzed, of which 94 children (40%) had been transfused with plasma during
      their PICU stay. Fifty-six episodes of nosocomial infections (51 children) were
      reported, yielding a nosocomial infection ratio of 24%. The unadjusted odds ratio
      for developing nosocomial infections associated with plasma transfusion was 4.1
      (95% CI, 2.1-7.9; p < 0.001). After adjusting for a propensity score, there was
      no difference between the two groups (adjusted odds ratio, 1.5; 95% CI, 0.5-4.0;
      p = 0.5). CONCLUSION: Plasma transfusion following cardiac surgery under
      cardiopulmonary bypass was not independently associated with the development of
      nosocomial infections in children (< 1 yr old) after adjustment for a propensity
      score.

PMID- 25560426
TI  - Prevalence of dysglycemia and association with outcomes in pediatric
      extracorporeal membrane oxygenation.
AB  - OBJECTIVES: To evaluate the relationship between glucose derangement, insulin
      administration, and mortality among children on extracorporeal membrane
      oxygenation. DESIGN: Retrospective cohort. SETTING: Tertiary PICU. PATIENTS: Two
      hundred nine children receiving extracorporeal membrane oxygenation, including 97
      neonates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hyperglycemia and
      severe hyperglycemia were defined as a single blood glucose level greater than 15
      mmol/L (270 mg/dL) and greater than 20 mmol/L (360 mg/dL), respectively.
      Hypoglycemia and severe hypoglycemia were defined as any single glucose level
      less than 3.3 mmol/L (60 mg/dL) and less than 2.2 mmol/L (40 mg/dL),
      respectively. A total of 15,912 glucose values were recorded. The median number
      of glucose values was 59 per patient, corresponding to a mean 0.53 +/- 0.12 tests
      per hour. Sixty-nine patients (33.0%) without dysglycemia and who received no
      insulin were defined as the control group. Eighty-nine (42.6%) and 26 (12.4%)
      patients developed hyperglycemia and severe hyperglycemia, respectively. Sixty
      three (30.1%) and 17 (8.1%) patients developed hypoglycemia and severe
      hypoglycemia, respectively. Sixty-one patients (29.2%) received IV insulin during
      extracorporeal membrane oxygenation. Both hyperglycemia and hypoglycemia were
      associated with increased mortality on extracorporeal membrane oxygenation (46%
      and 48%, respectively, vs 29% of controls; p = 0.03). However, after adjusting
      for severity of illness and extracorporeal membrane oxygenation complications,
      abnormal glucose levels were not independently related to mortality. CONCLUSIONS:
      Dysglycemia in children on extracorporeal membrane oxygenation was common but not
      independently associated with increased mortality. The optimal glucose range for
      this high-risk population requires further investigation.

PMID- 25560427
TI  - Association of left ventricular systolic function and vasopressor support with
      survival following pediatric out-of-hospital cardiac arrest.
AB  - OBJECTIVES: To characterize the association of hospital discharge survival with
      left ventricular systolic function evaluated by transthoracic echocardiography
      and vasoactive infusion support following return of spontaneous circulation after
      pediatric out-of-hospital cardiac arrest. DESIGN: Retrospective case series.
      SETTING: Single-center tertiary care pediatric cardiac arrest and critical care
      referral center. PATIENTS: Consecutive out-of-hospital cardiac arrest patients
      less than 18 years surviving to PICU admission who had a transthoracic
      echocardiography obtained by the clinical team within 24 hours of admission from
      January 2006 to May 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Fifty-eight patients had a post-return of spontaneous circulation transthoracic
      echocardiography performed within 24 hours of admission. The median time from
      return of spontaneous circulation to echo was 6.5 hours (interquartile range,
      4.7, 15.0 hr). Left ventricular systolic function was decreased in 24 of 58
      patients (41%). The mortality rate was 67% (39 of 58). Thirty-six patients (62%)
      received vasoactive infusions at the time of transthoracic echocardiography, and
      increased vasopressor inotropic score was associated with increased mortality on
      univariate analysis (p < 0.001). After controlling for defibrillation,
      vasopressor inotropic score, and interaction between vasopressor inotropic score
      and left ventricular systolic function, decreased left ventricular systolic
      function was associated with increased mortality (odds ratio, 13.7; 95% CI, 1.54
      122). CONCLUSIONS: In patients receiving transthoracic echocardiography within
      the first 24 hours following return of spontaneous circulation after pediatric
      out-of-hospital cardiac arrest, decreased left ventricular systolic function and
      vasopressor use were common. Decreased left ventricular systolic function was
      associated with increased mortality.

PMID- 25560428
TI  - Effect of high-dose continuous albuterol nebulization on clinical variables in
      children with status asthmaticus.
AB  - OBJECTIVES: Continuous albuterol nebulization is generally administered at 2.5-20
      mg/hr at most centers. We examined the effect of high-dose (75 or 150 mg/hr)
      albuterol on clinical variables in children with status asthmaticus. DESIGN:
      Retrospective analysis of inpatient medical records and prospectively collected
      computerized PICU respiratory therapy database. SETTING: Twenty-five-bed
      multidisciplinary PICU in a tertiary care children's hospital. PATIENTS: Children
      admitted to the PICU between January 2006 and December 2007 with status
      asthmaticus receiving high-dose continuous albuterol nebulization. (Those with
      cerebral palsy, cardiac pathology, and ventilator dependence were excluded.)
      INTERVENTIONS: : Chart review for PICU length of stay, albuterol dose, duration
      of nebulization, occurrence of chest pain, vomiting, tremors, hypokalemia (serum
      potassium < 3.0 mEq/L), and cardiac arrhythmia. Maximal heart rate, lowest
      diastolic blood pressure, and mean arterial pressure were compared to the
      variables at initiation of therapy and at hospital discharge. MEASUREMENTS AND
      MAIN RESULTS: Forty-two patients (22 boys and 20 girls) received high-dose
      continuous albuterol nebulization. Twenty-three received 75 mg/hr and 19 received
      150 mg/hr (3.7 mg/kg/hr [interquartile range, 2.4-5.8 mg/kg/hr]) for a duration
      of 22.3 hours (interquartile range, 6.6-31.7 hr). Heart rate increased and
      diastolic blood pressure and mean arterial pressure were significantly lower
      during nebulization compared to initiation of therapy or at hospital discharge (p
      < 0.05). No patient required fluid resuscitation or inotropic support, and one
      had self-limited premature ventricular contractions. Hypokalemia occurred in five
      of 33 patients who had serum electrolytes measured but did not require
      supplementation. One patient required endotracheal intubation after initiation of
      nebulization, and seven patients (16.7%) received noninvasive ventilation. PICU
      length of stay was 2.3 +/- 1.7 days; there were no deaths. CONCLUSIONS: High-dose
      continuous albuterol nebulization is associated with a low rate of subsequent
      mechanical ventilation and fairly short PICU length of stay without significant
      toxicity. Prospective studies comparing conventional and high-dose albuterol
      nebulization are needed to determine the optimum dose providing maximum efficacy
      with the least adverse effects.

PMID- 25560430
TI  - Isolated pediatric burn injury in Iraq and Afghanistan.
AB  - OBJECTIVES: To characterize the epidemiology of burn injury in pediatric patients
      and identify factors associated with mortality based on burn severity. DESIGN:
      Retrospective cohort study. SETTING: U.S. military combat support hospitals and
      forward surgical hospitals in Iraq and Afghanistan. PATIENTS: Iraqi and Afghan
      children less than 18 years old admitted with isolated burn injury.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Burn severity was classified
      as mild, moderate, and severe based on external Abbreviated Injury Scale score.
      Patient characteristics and outcomes were described according to burn severity. A
      multivariate logistic regression was performed on univariate associations with
      mortality. Of 4,743 pediatric patients, 549 (11.6%) had isolated burn injury.
      Overall mortality was 13%, median external Abbreviated Injury Scale was 3
      (interquartile range, 2-4), and 67% were male. Variables included in the logistic
      regression were external Abbreviated Injury Scale score, abnormal heart rate for
      age, hypotension, mechanical ventilation, transfusion, Glasgow Coma Scale,
      international normalized ratio, base deficit, hematocrit, and platelet count.
      Factors independently associated with mortality were international normalized
      ratio (odds ratio, 2.6; 95% CI, 1.2-5.8; p = 0.021) and external Abbreviated
      Injury Scale (odds ratio, 2.5; 95% CI, 1.3-4.7; p = 0.004). Mortality increased
      with burn severity: mild 1.7%, moderate 7.2%, and severe 47% (p < 0.001).
      CONCLUSIONS: This is the first in-depth study of pediatric burn injuries in
      combat. Children with severe burns (total body surface area > 39% or > 29% if < 5
      yr) had a high mortality and required significant resources in a setting that is
      not primarily resourced for long-term care of severe pediatric burn injury.
      Extraordinary measures are therefore used for the long-term care of these burned
      children within the war zones of Iraq and Afghanistan.

PMID- 25560429
TI  - Risk factors associated with iatrogenic opioid and benzodiazepine withdrawal in
      critically ill pediatric patients: a systematic review and conceptual model.
AB  - OBJECTIVES: Analgesia and sedation are common therapies in pediatric critical
      care, and rapid titration of these medications is associated with iatrogenic
      withdrawal syndrome. We performed a systematic review of the literature to
      identify all common and salient risk factors associated with iatrogenic
      withdrawal syndrome and build a conceptual model of iatrogenic withdrawal
      syndrome risk in critically ill pediatric patients. DATA SOURCES: Multiple
      databases, including PubMed/Medline, EMBASE, CINAHL, and the Cochrane Central
      Registry of Clinical Trials, were searched using relevant terms from January 1,
      1980, to August 1, 2014. STUDY SELECTION: Articles were included if they were
      published in English and discussed iatrogenic withdrawal syndrome following
      either opioid or benzodiazepine therapy in children in acute or intensive care
      settings. Articles were excluded if subjects were neonates born to opioid- or
      benzodiazepine-dependent mothers, children diagnosed as substance abusers, or
      subjects with cancer-related pain; if data about opioid or benzodiazepine
      treatment were not specified; or if primary data were not reported. DATA
      EXTRACTION: In total, 1,395 articles were evaluated, 33 of which met the
      inclusion criteria. To facilitate analysis, all opioid and/or benzodiazepine
      doses were converted to morphine or midazolam equivalents, respectively. A table
      of evidence was developed for qualitative analysis of common themes, providing a
      framework for the construction of a conceptual model. The strongest risk factors
      associated with iatrogenic withdrawal syndrome include duration of therapy and
      cumulative dose. Additionally, evidence exists linking patient, process, and
      system factors in the development of iatrogenic withdrawal syndrome. FINDINGS:
      Most articles were prospective observational or interventional studies.
      CONCLUSIONS: Given the state of existing evidence, well-designed prospective
      studies are required to better characterize iatrogenic withdrawal syndrome in
      critically ill pediatric patients. This review provides data to support the
      construction of a conceptual model of iatrogenic withdrawal syndrome risk that,
      if supported, could be useful in guiding future research.

PMID- 25560431
TI  - Expression and characterization of Streptomyces coelicolor serine/threonine
      protein kinase PkaE.
AB  - We identified and characterized a new eukaryotic-type protein kinase (PkaE) from
      Streptomyces coelicolor A3 (2) M145. PkaE, consisting of 510 amino acid residues,
      is a cytoplasmic protein kinase and contains the catalytic domain of eukaryotic
      protein kinases in the N-terminal region. Recombinant PkaE was found to be
      autophosphorylated at threonine residues only. The disruption of chromosomal pkaE
      resulted in the overproduction of the actinorhodin-related blue pigment
      antibiotics. pkaE was expressed during the late growth phase in S. coelicolor A3
      (2) M145, which corresponded to the production time of blue pigments. This result
      indicated that PkaE acts as a negative regulator for production of the secondary
      metabolites. In addition, PkaE was able to phosphorylate KbpA, a regulator
      involved in the AfsK-AfsR regulatory pathway. 

PMID- 25560432
TI  - Current status of viral expression systems in plants and perspectives for oral
      vaccines development.
AB  - During the last 25 years, the technology to produce recombinant vaccines in plant
      cells has evolved from modest proofs of the concept to viable technologies
      adopted by some companies due to significant improvements in the field. Viral
      based expression strategies have importantly contributed to this success owing to
      high yields, short production time (which is in most cases free of tissue culture
      steps), and the implementation of confined processes for production under GMPs.
      Herein the distinct expression systems based on viral elements are analyzed. This
      review also presents the outlook on how these technologies have been successfully
      applied to the development of plant-based vaccines, some of them being in
      advanced stages of development. Perspectives on how viral expression systems
      could allow for the development of innovative oral vaccines constituted by
      minimally-processed plant biomass are discussed. 

PMID- 25560433
TI  - Epigenetic States of nephron progenitors and epithelial differentiation.
AB  - In mammals, formation of new nephrons ends perinatally due to consumption of
      mesenchymal progenitor cells. Premature depletion of progenitors due to
      prematurity or postnatal loss of nephrons due to injury causes chronic kidney
      disease and hypertension. Intensive efforts are currently invested in designing
      regenerative strategies to form new nephron progenitors from pluripotent cells,
      which upon further differentiation provide a potential source of new nephrons. To
      know if reprogramed renal cells can maintain their identity and fate requires
      knowledge of the epigenetic states of native nephron progenitors and their
      progeny. In this article, we summarize current knowledge and gaps in the
      epigenomic landscape of the developing kidney. We now know that Pax2/PTIP/H3K4
      methyltransferase activity provides the initial epigenetic specification signal
      to the metanephric mesenchyme. During nephrogenesis, the cap mesenchyme housing
      nephron progenitors is enriched in bivalent chromatin marks; as tubulogenesis
      proceeds, the tubular epithelium acquires H3K79me2. The latter mark is uniquely
      induced during epithelial differentiation. Analysis of histone landscapes in
      clonal metanephric mesenchyme cell lines and in Wilms tumor and normal fetal
      kidney has revealed that promoters of poised nephrogenesis genes carry bivalent
      histone signatures in progenitors. Differentiation or stimulation of Wnt
      signaling promotes resolution of bivalency; this does not occur in Wilms tumor
      cells consistent with their developmental arrest. The use of small cell number
      ChIP-Seq should facilitate the characterization of the chromatin landscape of the
      metanephric mesenchyme and various nephron compartments during nephrogenesis.
      Only then we will know if stem and somatic cell reprogramming into kidney
      progenitors recapitulates normal development.

PMID- 25560434
TI  - Keeping primary care "in the loop": General practitioners want better
      communication with specialists and hospitals when caring for people diagnosed
      with cancer.
AB  - AIM: To investigate general practitioners' (GP) perceptions about communication
      when providing cancer care. METHODS: A self-report survey, which included an open
      response section, was mailed to a random sample of 1969 eligible Australian GPs.
      Content analysis of open response comments pertaining to communication was
      undertaken in order to ascertain GPs' views about communication issues in the
      provision of cancer care. RESULTS: Of the 648 GPs who completed the survey, 68
      (10%) included open response comments about interprofessional communication.
      Participants who commented on communication were a median age of 50 years and
      worked 33 h/week; 28% were male and 59% practiced in the metropolitan area.
      Comments pertaining to communication were coded using five non-mutually exclusive
      categories: being kept in the loop; continuity of care; relationships with
      specialists; positive communication experiences; and strategies for improving
      communication.GPs repeatedly noted the importance of receiving detailed and
      timely communication from specialists and hospitals, particularly in relation to
      patients' treatment regimes and follow-up care. Several GPs remarked that they
      were left out of "the information loop" and that patients were "lost" or "dumped"
      after referral. CONCLUSION: While many GPs are currently involved in some aspects
      of cancer management, detailed and timely communication between specialists and
      GPs is imperative to support shared care and ensure optimal patient outcomes.
      This research highlights the need for established channels of communication
      between specialist and primary care medicine to support greater involvement by
      GPs in cancer care.

PMID- 25560435
TI  - Sleep duration, restfulness, and screens in the sleep environment.
AB  - BACKGROUND AND OBJECTIVE: Associations of inadequate sleep with numerous health
      outcomes among youth necessitate identifying its modifiable determinants.
      Television (TV) has been associated with sleep curtailment, but little is known
      about small screens (eg, smartphones), which can be used in bed and emit
      notifications. Therefore, we examined associations of different screens in sleep
      environments with sleep duration and perceived insufficient rest or sleep.
      METHODS: Participants included 2048 fourth- and seventh-graders participating in
      the Massachusetts Childhood Obesity Research Demonstration Study in 2012 to 2013.
      Using linear and log binomial regression, we examined cross-sectional
      associations of small screens and TVs in sleep environments and screen time with
      weekday sleep duration and perceived insufficient rest or sleep in the past week.
      RESULTS: Children who slept near a small screen (compared with never) reported
      20.6 fewer minutes of sleep (95% confidence interval [CI], -29.7 to -11.4) and
      had a higher prevalence of perceived insufficient rest or sleep (prevalence
      ratio, 1.39; 95% CI, 1.21 to 1.60). Children who slept in a room with a TV
      (compared with no TV) reported 18.0 fewer minutes of sleep (95% CI, -27.9 to 
      8.1). TV or DVD viewing and video or computer game playing were associated with
      both sleep outcomes (P < .01). Some associations were stronger among Hispanic,
      non-Hispanic black, and older children (P < .05 for heterogeneity). CONCLUSIONS:
      Sleeping near a small screen, sleeping with a TV in the room, and more screen
      time were associated with shorter sleep durations. Presence of a small screen,
      but not a TV, in the sleep environment and screen time were associated with
      perceived insufficient rest or sleep. These findings caution against unrestricted
      screen access in children's bedrooms.

PMID- 25560437
TI  - Paternal depression in the postnatal period and child development: mediators and
      moderators.
AB  - OBJECTIVE: To explore potential mediating and moderating factors that influence
      the association between paternal depression in the postnatal period and
      subsequent child behavioral and emotional problems. METHODS: A population-based
      cohort (N = 13,822) from the Avon Longitudinal Study of Parents and Children
      (ALSPAC) was recruited during pregnancy. Paternal and maternal depressive
      symptoms were assessed with the Edinburgh Postnatal Depression Scale at 8 weeks
      after the birth of the child. Child outcomes were assessed at 3.5 years by using
      the Rutter revised preschool scales and at 7 years by using the Strengths and
      Difficulties Questionnaire. Path analysis was used to assess hypothesized
      mediators (ie, depression in the other parent, couple conflict, and paternal
      noninvolvement) of the associations between both paternal and maternal depression
      and child outcomes. We also tested for hypothesized moderators (ie, paternal
      education and antisocial traits). RESULTS: Family factors (maternal depression
      and couple conflict) mediated two-thirds of the overall association between
      paternal depression and child outcomes at 3.5 years. Similar findings were seen
      when children were 7 years old. In contrast, family factors mediated less than
      one-quarter of the association between maternal depression and child outcomes.
      There was no evidence of moderating effects of either parental education or
      antisocial traits. CONCLUSIONS: The majority of the association between
      depression in fathers postnatally and subsequent child behavior is explained by
      the mediating role of family environment, whereas the association between
      depression in mothers and child outcomes appears to be better explained by other
      factors, perhaps including direct mother-infant interaction.

PMID- 25560436
TI  - Partnering health disparities research with quality improvement science in
      pediatrics.
AB  - Disparities in pediatric health care quality are well described in the
      literature, yet practical approaches to decreasing them remain elusive. Quality
      improvement (QI) approaches are appealing for addressing disparities because they
      offer a set of strategies by which to target modifiable aspects of care delivery
      and a method for tailoring or changing an intervention over time based on data
      monitoring. However, few examples in the literature exist of QI interventions
      successfully decreasing disparities, particularly in pediatrics, due to well
      described challenges in developing, implementing, and studying QI with vulnerable
      populations or in underresourced settings. In addition, QI interventions aimed at
      improving quality overall may not improve disparities, and in some cases, may
      worsen them if there is greater uptake or effectiveness of the intervention among
      the population with better outcomes at baseline. In this article, the authors
      review some of the challenges faced by researchers and frontline clinicians
      seeking to use QI to address health disparities and propose an agenda for moving
      the field forward. Specifically, they propose that those designing and
      implementing disparities-focused QI interventions reconsider comparator groups,
      use more rigorous evaluation methods, carefully consider the evidence for
      particular interventions and the context in which they were developed, directly
      engage the social determinants of health, and leverage community resources to
      build collaborative networks and engage community members. Ultimately, new
      partnerships between communities, providers serving vulnerable populations, and
      QI researchers will be required for QI interventions to achieve their potential
      related to health care disparity reduction. 

PMID- 25560438
TI  - Safety of measles-containing vaccines in 1-year-old children.
AB  - BACKGROUND AND OBJECTIVES: All measles-containing vaccines are associated with
      several types of adverse events, including seizure, fever, and immune
      thrombocytopenia purpura (ITP). Because the measles-mumps-rubella-varicella
      (MMRV) vaccine compared with the separate measles-mumps-rubella (MMR) and
      varicella (MMR + V) vaccine increases a toddler's risk for febrile seizures, we
      investigated whether MMRV is riskier than MMR + V and whether either vaccine
      elevates the risk for additional safety outcomes. METHODS: Study children were
      aged 12 to 23 months in the Vaccine Safety Datalink from 2000 to 2012. Nine study
      outcomes were investigated: 7 main outcomes (anaphylaxis, ITP, ataxia, arthritis,
      meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki
      disease), seizure, and fever. Comparing MMRV with MMR + V, relative risk was
      estimated by using stratified exact binomial tests. Secondary analyses examined
      post-MMRV or MMR + V risk versus comparison intervals; risk and comparison
      intervals were then contrasted for MMRV versus MMR+V. RESULTS: We evaluated
      123,200 MMRV and 584,987 MMR + V doses. Comparing MMRV with MMR + V, risks for
      the 7 main outcomes were not significantly different. Several outcomes had few or
      zero postvaccination events. Comparing risk versus comparison intervals, ITP risk
      was higher after MMRV (odds ratio [OR]: 11.3 [95% confidence interval (CI): 1.9
      to 68.2]) and MMR + V (OR: 10 [95% CI: 4.5 to 22.5]) and ataxia risk was lower
      after both vaccines (MMRV OR: 0.8 [95% CI: 0.5 to 1]; MMR + V OR: 0.8 [95% CI:
      0.7 to 0.9]). Compared with MMR + V, MMRV increased risk of seizure and fever 7
      to 10 days after vaccination. CONCLUSIONS: This study did not identify any new
      safety concerns comparing MMRV with MMR + V or after either the MMRV or the MMR +
      V vaccine. This study provides reassurance that these outcomes are unlikely after
      either vaccine.

PMID- 25560439
TI  - The recommendation for rest following acute concussion.

PMID- 25560440
TI  - Recognizing the importance of the social determinates of health.

PMID- 25560441
TI  - Supporting fatherhood before and after it happens.

PMID- 25560442
TI  - Talking with parents about end-of-life decisions for their children.
AB  - BACKGROUND AND OBJECTIVE: Retrospective studies show that most parents prefer to
      share in decisions to forgo life-sustaining treatment (LST) from their children.
      We do not yet know how physicians and parents communicate about these decisions
      and to what extent parents share in the decision-making process. METHODS: We
      conducted a prospective exploratory study in 2 Dutch University Medical Centers.
      RESULTS: Overall, 27 physicians participated, along with 37 parents of 19
      children for whom a decision to withhold or withdraw LST was being considered.
      Forty-seven conversations were audio recorded, ranging from 1 to 8 meetings per
      patient. By means of a coding instrument we quantitatively and qualitatively
      analyzed physicians' and parents' communicative behaviors. On average, physicians
      spoke 67% of the time, parents 30%, and nurses 3%. All physicians focused
      primarily on providing medical information, explaining their preferred course of
      action, and informing parents about the decision being reached by the team. Only
      in 2 cases were parents asked to share in the decision-making. Despite their
      intense emotions, most parents made great effort to actively participate in the
      conversation. They did this by asking for clarifications, offering their
      preferences, and reacting to the decision being proposed (mostly by expressing
      their assent). In the few cases where parents strongly preferred LST to be
      continued, the physicians either gave parents more time or revised the decision.
      CONCLUSIONS: We conclude that parents are able to handle a more active role than
      they are currently being given. Parents' greatest concern is that their child
      might suffer.

PMID- 25560443
TI  - A new commitment to newborn survival.

PMID- 25560444
TI  - Benefits of strict rest after acute concussion: a randomized controlled trial.
AB  - OBJECTIVES: To determine if recommending strict rest improved concussion recovery
      and outcome after discharge from the pediatric emergency department (ED).
      METHODS: Patients aged 11 to 22 years presenting to a pediatric ED within 24
      hours of concussion were recruited. Participants underwent neurocognitive,
      balance, and symptom assessment in the ED and were randomized to strict rest for
      5 days versus usual care (1-2 days rest, followed by stepwise return to
      activity). Patients completed a diary used to record physical and mental activity
      level, calculate energy exertion, and record daily postconcussive symptoms.
      Neurocognitive and balance assessments were performed at 3 and 10 days
      postinjury. Sample size calculations were powered to detect clinically meaningful
      differences in postconcussive symptom, neurocognitive, and balance scores between
      treatment groups. Linear mixed modeling was used to detect contributions of group
      assignment to individual recovery trajectory. RESULTS: Ninety-nine patients were
      enrolled; 88 completed all study procedures (45 intervention, 43 control).
      Postdischarge, both groups reported a 20% decrease in energy exertion and
      physical activity levels. As expected, the intervention group reported less
      school and after-school attendance for days 2 to 5 postconcussion (3.8 vs 6.7
      hours total, P < .05). There was no clinically significant difference in
      neurocognitive or balance outcomes. However, the intervention group reported more
      daily postconcussive symptoms (total symptom score over 10 days, 187.9 vs 131.9,
      P < .03) and slower symptom resolution. CONCLUSIONS: Recommending strict rest for
      adolescents immediately after concussion offered no added benefit over the usual
      care. Adolescents' symptom reporting was influenced by recommending strict rest.

PMID- 25560445
TI  - Arrived: the crisis of unaccompanied children at our southern border.

PMID- 25560446
TI  - Duration of pertussis immunity after DTaP immunization: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Pertussis incidence is increasing, possibly due to the
      introduction of acellular vaccines, which may have decreased the durability of
      immune response. We sought to evaluate and compare the duration of protective
      immunity conferred by a childhood immunization series with 3 or 5 doses of
      diphtheria-tetanus-acellular pertussis (DTaP). METHODS: We searched Medline and
      Embase for articles published before October 10, 2013. Included studies contained
      a measure of long-term immunity to pertussis after 3 or 5 doses of DTaP. Twelve
      articles were eligible for inclusion; 11 of these were included in the meta
      analysis. We assessed study quality and used meta-regression models to evaluate
      the relationship between the odds of pertussis and time since last dose of DTaP
      and to estimate the probability of vaccine failure through time. RESULTS: We
      found no significant difference between the annual odds of pertussis for the 3-
      versus 5-dose DTaP regimens. For every additional year after the last dose of
      DTaP, the odds of pertussis increased by 1.33 times (95% confidence interval:
      1.23-1.43). Assuming 85% vaccine efficacy, we estimated that 10% of children
      vaccinated with DTaP would be immune to pertussis 8.5 years after the last dose.
      Limitations included the statistical model extrapolated from data and the
      different study designs included, most of which were observational study designs.
      CONCLUSIONS: Although acellular pertussis vaccines are considered safer, the
      adoption of these vaccines may necessitate earlier booster vaccination and
      repeated boosting strategies to achieve necessary "herd effects" to control the
      spread of pertussis.

PMID- 25560447
TI  - Bullying and suicidal ideation and behaviors: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Over the last decade there has been increased
      attention to the association between bullying involvement (as a victim,
      perpetrator, or bully-victim) and suicidal ideation/behaviors. We conducted a
      meta-analysis to estimate the association between bullying involvement and
      suicidal ideation and behaviors. METHODS: We searched multiple online databases
      and reviewed reference sections of articles derived from searches to identify
      cross-sectional studies published through July 2013. Using search terms
      associated with bullying, suicide, and youth, 47 studies (38.3% from the United
      States, 61.7% in non-US samples) met inclusion criteria. Seven observers
      independently coded studies and met in pairs to reach consensus. RESULTS: Six
      different meta-analyses were conducted by using 3 predictors (bullying
      victimization, bullying perpetration, and bully/victim status) and 2 outcomes
      (suicidal ideation and suicidal behaviors). A total of 280 effect sizes were
      extracted and multilevel, random effects meta-analyses were performed. Results
      indicated that each of the predictors were associated with risk for suicidal
      ideation and behavior (range, 2.12 [95% confidence interval (CI), 1.67-2.69] to
      4.02 [95% CI, 2.39-6.76]). Significant heterogeneity remained across each
      analysis. The bullying perpetration and suicidal behavior effect sizes were
      moderated by the study's country of origin; the bully/victim status and suicidal
      ideation results were moderated by bullying assessment method. CONCLUSIONS:
      Findings demonstrated that involvement in bullying in any capacity is associated
      with suicidal ideation and behavior. Future research should address mental health
      implications of bullying involvement to prevent suicidal ideation/behavior.

PMID- 25560449
TI  - A practical approach to classifying and managing feeding difficulties.
AB  - Many young children are thought by their parents to eat poorly. Although the
      majority of these children are mildly affected, a small percentage have a serious
      feeding disorder. Nevertheless, even mildly affected children whose anxious
      parents adopt inappropriate feeding practices may experience consequences.
      Therefore, pediatricians must take all parental concerns seriously and offer
      appropriate guidance. This requires a workable classification of feeding problems
      and a systematic approach. The classification and approach we describe
      incorporate more recent considerations by specialists, both medical and
      psychological. In our model, children are categorized under the 3 principal
      eating behaviors that concern parents: limited appetite, selective intake, and
      fear of feeding. Each category includes a range from normal (misperceived) to
      severe (behavioral and organic). The feeding styles of caregivers (responsive,
      controlling, indulgent, and neglectful) are also incorporated. The objective is
      to allow the physician to efficiently sort out the wide variety of conditions,
      categorize them for therapy, and where necessary refer to specialists in the
      field. 

PMID- 25560448
TI  - Addressing social determinants of health at well child care visits: a cluster
      RCT.
AB  - OBJECTIVE: To evaluate the effect of a clinic-based screening and referral system
      (Well Child Care, Evaluation, Community Resources, Advocacy, Referral, Education
      [WE CARE]) on families' receipt of community-based resources for unmet basic
      needs. METHODS: We conducted a cluster randomized controlled trial at 8 urban
      community health centers, recruiting mothers of healthy infants. In the 4 WE CARE
      clinics, mothers completed a self-report screening instrument that assessed needs
      for child care, education, employment, food security, household heat, and
      housing. Providers made referrals for families; staff provided requisite
      applications and telephoned referred mothers within 1 month. Families at the 4
      control community health centers received the usual care. We analyzed the results
      with generalized mixed-effect models. RESULTS: Three hundred thirty-six mothers
      were enrolled in the study (168 per arm). The majority of families had household
      incomes <$20,000 (57%), and 68% had >= 2 unmet basic needs. More WE CARE mothers
      received >= 1 referral at the index visit (70% vs 8%; adjusted odds ratio [aOR] =
      29.6; 95% confidence interval [CI], 14.7-59.6). At the 12-month visit, more WE
      CARE mothers had enrolled in a new community resource (39% vs 24%; aOR = 2.1; 95%
      CI, 1.2-3.7). WE CARE mothers had greater odds of being employed (aOR = 44.4; 95%
      CI, 9.8-201.4). WE CARE children had greater odds of being in child care (aOR =
      6.3; 95% CI, 1.5-26.0). WE CARE families had greater odds of receiving fuel
      assistance (aOR = 11.9; 95% CI, 1.7-82.9) and lower odds of being in a homeless
      shelter (aOR = 0.2; 95% CI, 0.1-0.9). CONCLUSIONS: Systematically screening and
      referring for social determinants during well child care can lead to the receipt
      of more community resources for families.

PMID- 25560450
TI  - Identifying molecular subtypes related to clinicopathologic factors in pancreatic
      cancer.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal
      tumors and usually presented with locally advanced and distant metastasis
      disease, which prevent curative resection or treatments. In this regard, we
      considered identifying molecular subtypes associated with clinicopathological
      factor as prognosis factors to stratify PDAC for appropriate treatment of
      patients. RESULTS: In this study, we identified three molecular subtypes which
      were significant on survival time and metastasis. We also identified significant
      genes and enriched pathways represented for each molecular subtype. Considering
      R0 resection patients included in each subtype, metastasis and survival times are
      significantly associated with subtype 1 and subtype 2. CONCLUSIONS: We observed
      three PDAC molecular subtypes and demonstrated that those subtypes were
      significantly related with metastasis and survival time. The study may have
      utility in stratifying patients for cancer treatment.

PMID- 25560451
TI  - Sensitive determination of parabens in human urine and serum using methacrylate
      monoliths and reversed-phase capillary liquid chromatography-mass spectrometry.
AB  - A method for the determination of parabens in human urine and serum by capillary
      liquid chromatography (cLC) with UV-Vis and mass spectrometry (MS) detection
      using methacrylate ester-based monolithic columns has been developed. The
      influence of composition of polymerization mixture was studied. The optimum
      monolith was obtained with butyl methacrylate monomer at 60/40% (wt/wt) butyl
      methacrylate/ethylene dimethacrylate ratio and 50wt% porogens (composed of 36wt%
      of 1,4-butanediol, 54wt% 1-propanol and 10wt% water). Baseline resolution of
      analytes was achieved through a mobile phase of acetonitrile/water in gradient
      elution mode. Additionally, dispersive liquid-liquid microextraction (DLLME) was
      combined with both cLC-UV-Vis and cLC-MS to achieve the determination of parabens
      in human urine and serum samples with very low limits of detection. Satisfactory
      intra- and inter-day repeatabilities were obtained in UV-Vis and MS detection,
      although the latter provided lower detection limits (up to 300-fold) than the UV
      Vis detection. Recoveries for the target analytes from spiked biological samples
      ranged from 95.2% to 106.7%. The proposed methodology for the ultra-low
      determination of parabens in human urine and serum samples is simple and fast,
      the consumption of reagents is very low, and very small samples can be analyzed. 

PMID- 25560453
TI  - Application of nonionic surfactant as a new method for the enhancement of
      electromembrane extraction performance for determination of basic drugs in
      biological samples.
AB  - This paper proposes for the first time the use of a nonionic surfactant for the
      enhancement of electromembrane extraction performance. The presence of nonionic
      surfactant in donor phase promotes ionic analytes efficient migration through the
      organic liquid membrane. Surfactant assisted electromembrane extraction coupled
      with capillary electrophoresis was used for the extraction of basic drugs
      (methamphetamine, ephedrine and methadone) from biological samples. Parameters
      that affect the extraction efficiency were investigated and optimized for the
      proposed method. Optimal extractions were accomplished with 2-nitrophenyl octyl
      ether as the supported liquid membrane, with 125V as the driving force and 0.2mM
      Triton X-100 with pH 5.0 in donor and pH 1 in acceptor solutions. Equilibrium
      extraction conditions were obtained after 20min of operation where the whole
      assembly agitated at 1000rpm. Under the optimum experimental conditions, good
      limits of detection (0.90-2.42ngmL(-1)), linearities (R(2)>0.9995), and
      repeatability of extraction (RSDs below 4.4%, n=5) were obtained. Finally, the
      developed method was applied to drug level monitoring in the biological samples
      including hair and urine samples and satisfactory results were obtained. 

PMID- 25560452
TI  - Three column intermittent simulated moving bed chromatography: 3. Cascade
      operation for center-cut separations.
AB  - A general design methodology for chromatographic three fraction separation by
      application of the three column intermittent simulated moving bed (3C-ISMB)
      cascade is proposed and experimentally validated by studying the purification of
      an intermediately retained stereoisomer of nadolol, from an equimolar mixture of
      its four stereoisomers. The theoretical part shows that the 3C-ISMB cascade can
      be easily designed by applying Triangle Theory. Moreover, a re-scaling approach
      for the second stage is proposed so as to account for the fact that the feed flow
      rates to stage 2 are generally higher as compared to stage 1 due to dilution in
      the latter. Scaling the columns of the second stage accordingly enables to run
      both stages under optimal conditions with respect to switching time and step
      ratio, which is an important advantage as compared to integrated ternary
      processes. The experimental part starts with studying the linear adsorption
      behavior of nadolol in heptane/ethanol/DEA on Chiralpak AD for varying ratios of
      heptane and ethanol. Based on that, a solvent composition of Hept/EtOH/DEA
      30/70/0.3 (v/v/v) is selected and the competitive multi-component Langmuir
      isotherm of the quaternary mixture is determined by frontal analysis. The
      resulting isotherm parameters are used to design several first stage experiments
      aiming at removal of the most retained component. The resulting ternary
      intermediate product is reprocessed in several second stage experiments studying
      various configurations. Finally, the dilution of the intermediate product with
      Hept/DEA yielding a solvent composition of Hept/EtOH/DEA 60/40/0.3 (v/v/v) is
      examined showing that the resulting increase in retention is beneficial for final
      product purities. Moreover, the reduction in viscosity compensates for the
      dilution as it enables higher flow rates. Dilution of the intermediate product is
      hence the best option, yielding highest overall cascade productivity (2.10gl(
      1)h(-1)) and highest product purity (97.8%) requiring a specific solvent
      consumption of 12l/g of product. 

PMID- 25560454
TI  - Development of a new separation media using ultra-thin glassy carbon film
      modified silica.
AB  - A self-polymerizable octatetrayne, 1,8-dialdehydebenzyl-1,3,5,7-octatetrayne, is
      synthesized and covalently attached to an amino-functionalized surface of silica
      particles. The silica particles with a monolayer coverage of octatetrayne were
      then thermally processed to various final temperatures of 200, 400 and 700
      degrees C. The amino-functionalization, covalent attachment of octatetrayne and
      thermal process of silica particles were monitored by scanning electron
      microscopy (SEM), infrared (IR) spectroscopy and thermogravimetric analysis
      (TGA). The thermally processed particles were then packed into a capillary column
      and evaluated as a stationary phase for HPLC. After chromatographic evaluation,
      the optimized temperature for thermal processing was determined to be 400 degrees
      C, which provides the best modified silica particles SiO2-OCT-T400 with an ultra
      thin glassy carbon film coating. The linear solvation energy relationship model
      indicated that the primary contributors in retention are dispersion and H-bond
      basicity. The application of SiO2-OCT-T400 as a stationary phase was further
      demonstrated by successful separation of nonpolar hydrocarbons mixture and a
      nucleosides mixture. 

PMID- 25560455
TI  - Graphene-derivatized silica as an efficient solid-phase extraction sorbent for
      pre-concentration of fluoroquinolones from water followed by liquid
      chromatography fluorescence detection.
AB  - This work presents a novel analytical method based on graphene for the
      determination of five widely used fluoroquinolones (FQs) in aqueous matrices. The
      procedure entails solid-phase extraction (SPE) on graphene-derivatized silica
      (200mg), followed by liquid chromatography with fluorescence detection. Monolayer
      graphene oxide (GO) flakes were covalently bonded onto aminopropyl silica
      microparticles, and then treated with aqueous hydrazine to obtain the reduced GO
      (RGO). The final material (RGO-silica) was characterized by thermogravimetric
      analysis (TGA), scanning electron microscopy (SEM) and BET analysis, and for the
      first time evaluated as mixed-mode sorbent for the SPE of FQs from natural
      waters. Accuracy was studied on tap/raw river water in the concentration range 5
      10,000ngL(-1), obtaining mean absolute recoveries from 72 to 118%. The inter-day
      precision was good, showing relative standard deviations (RSDs) in the range 5
      15%. Sample volumes up to 1L provided enrichment factors up to 1000, achieving
      accurate quantification of concentrations as low as 5ngL(-1). The analytes were
      simultaneously and quantitatively eluted from the RGO-silica cartridge in a
      single fraction by using acetonitrile combined with aqueous tetrabutyl ammonium
      hydroxide. The batch-to-batch reproducibility was verified on three independently
      prepared RGO-silica samples. RGO-silica was advantageous in terms of adsorption
      capacity and reusability with respect to commercial sorbents; the cartridge
      proved to be reusable for at least 10 consecutive extractions, with no
      significant loss of efficiency (recovery >70%). The analytical procedure was
      applied to the determination of FQs in actual environmental waters. 

PMID- 25560456
TI  - Evaluation of 2,3-epoxypropyl groups and functionalization yield in glycidyl
      methacrylate monoliths using gas chromatography.
AB  - Poly(glycidyl methacrylate-co-ethylene dimethacrylate) (poly(GMA-co-EDMA)) is
      most frequently used as parent monolith to obtain stationary phases with a
      variety of surface chemistries for liquid chromatography and capillary
      electrochromatography. Functionalization is performed by opening the accessible
      2,3-epoxypropyl groups of the monolith with a suitable reagent. The number of 2,3
      epoxypropyl groups which are accessible before and after the functionalization
      reaction, and the grafting yield, are important parameters, required both to
      optimize functionalization and to interpret the chromatographic performance of
      functionalized monoliths. In this work, a method capable of providing this
      information for parent and functionalized poly(GMA-co-EDMA) monoliths prepared
      both in silica capillaries and in other supports is proposed. First, sulfuric
      acid and lithium aluminium hydride (LiAlH4) are sequentially used to release the
      2,3-epoxypropyl groups as glycerol, which is subsequently determined by GC. About
      6.0mmol of 2,3-epoxypropyl groups per gram of monolith was found in this work for
      the parent monoliths prepared in silica capillaries using UV-initiation. The
      monoliths were also functionalized using ammonia (NH3), diethylamine (DEA) and
      epinephrine, and the amount of residual 2,3-epoxypropyl groups, and hence the
      functionalization yield, were established by also measuring the GC peak of
      glycerol. The amounts of 2,3-epoxypropyl groups and the derivatization yields
      were established with RSDs of 1.7 and 3.4%, respectively. The proposed method was
      also applied to the characterization of poly(GMA-co-EDMA) monoliths prepared in
      glass vials. Significant differences with respect to those prepared in 100MUm
      I.D. silica capillaries were evidenced. 

PMID- 25560457
TI  - The relationship between serum potassium, potassium variability and in-hospital
      mortality in critically ill patients and a before-after analysis on the impact of
      computer-assisted potassium control.
AB  - INTRODUCTION: The relationship between potassium regulation and outcome is not
      known. Our first aim in the present study was to determine the relationship
      between potassium level and variability in (ICU) stay and outcome. The second aim
      was to evaluate the impact of a computer-assisted potassium regulation protocol.
      METHODS: We performed a retrospective before-after study including all patients
      >15 years of age admitted for more than 24 hours to the ICU of our university
      teaching hospital between 2002 and 2011. Potassium control was fully integrated
      with computerized glucose control (glucose and potassium regulation program for
      intensive care patients (GRIP-II)). The potassium metrics that we determined
      included mean potassium, potassium variability (defined as the standard deviation
      of all potassium levels) and percentage of ICU time below and above the reference
      range (3.5 through 5.0 mmol/L). These metrics were determined for the first ICU
      day (early phase) and the subsequent ICU days (late phase; that is, day 2 to day
      7). We also compared potassium metrics and in-hospital mortality before and after
      GRIP-II was implemented in 2006. RESULTS: Of all 22,347 ICU admissions, 10,451
      (47%) patients were included. A total of 206,987 potassium measurements were
      performed in these patients. Glucose was regulated by GRIP-II in 4,664 (45%)
      patients. The overall in-hospital mortality was 22%. There was a U-shaped
      relationship between the potassium level and in-hospital mortality (P <0.001).
      Moreover, potassium variability was independently associated with outcome. After
      implementation of GRIP-II, in the late phase the time below 3.5 mmol/L decreased
      from 9.2% to 3.9% and the time above 5.0 mmol/L decreased from 6.1% to 5.2%, and
      potassium variability decreased from 0.31 to 0.26 mmol/L (all P <0.001). The
      overall decrease in in-hospital mortality from 23.3% before introduction of GRIP
      II to 19.9% afterward (P <0.001) was not related to a specific potassium
      subgroup. CONCLUSIONS: Hypokalemia, hyperkalemia and potassium variability were
      independently associated with increased mortality. Computerized potassium control
      clearly resulted in improved potassium metrics.

PMID- 25560458
TI  - Modulation of the Dirac point voltage of graphene by ion-gel dielectrics and its
      application to soft electronic devices.
AB  - We investigated systematic modulation of the Dirac point voltage of graphene
      transistors by changing the type of ionic liquid used as a main gate dielectric
      component. Ion gels were formed from ionic liquids and a non-triblock-copolymer
      based binder involving UV irradiation. With a fixed cation (anion), the Dirac
      point voltage shifted to a higher voltage as the size of anion (cation)
      increased. Mechanisms for modulation of the Dirac point voltage of graphene
      transistors by designing ionic liquids were fully understood using molecular
      dynamics simulations, which excellently matched our experimental results. It was
      found that the ion sizes and molecular structures play an essential role in the
      modulation of the Dirac point voltage of the graphene. Through control of the
      position of their Dirac point voltages on the basis of our findings,
      complementary metal-oxide-semiconductor (CMOS)-like graphene-based inverters
      using two different ionic liquids worked perfectly even at a very low source
      voltage (V(DD) = 1 mV), which was not possible for previous works. These results
      can be broadly applied in the development of low-power-consumption,
      flexible/stretchable, CMOS-like graphene-based electronic devices in the future.

PMID- 25560459
TI  - Divergent effect of liver X receptor agonists on prostate-specific antigen
      expression is dependent on androgen receptor in prostate carcinoma cells.
AB  - BACKGROUND: Liver X receptor (LXR) isoforms, LXRalpha and LXRbeta, have similar
      protein structures and ligands, but diverse tissue distribution. We used two
      synthetic, non-steroidal LXR agonists, T0901317 and GW3965, to investigate the
      effects of LXR agonist modulation on prostate specific antigen (PSA) via the
      expressions of androgen receptors (AR), LXRalpha, or LXRbeta, in prostate
      carcinoma cells. METHODS: LXRalpha- or LXRbeta-knockdown cells were transduced
      with specific shRNA lentiviral particles. LXRalpha and LXRbeta expressions were
      assessed by immunoblotting and RT-qPCR assays. Cell proliferation was determined
      by (3) H-thymidine incorporation assays. The effects of LXR agonists and
      epigallocatechin gallate (EGCG) on PSA expression were determined by ELISA,
      immunoblotting, or transient gene expression assays. RESULTS: Treatment with
      either T0901317 or GW3965 significantly attenuated cell proliferation of LNCaP
      cells. T0901317 treatment suppressed PSA expression while GW3965 treatment
      enhanced PSA expression. The increase of PSA promoter activity by GW3965 was
      dependent on the expression of AR. Either LXRalpha- or LXRbeta-knockdown did not
      affect the activation of androgen on PSA gene expression. However, as compared
      with mock knockdown-LNCaP cells, the LXRalpha-knockdown but not the LXRbeta
      knockdown attenuated the effects of T0901317 and GW3965 on PSA expressions. The
      effect of GW3965 on PSA expression was blocked by the addition of EGCG.
      CONCLUSIONS: Our results indicate that T0901317 and GW3965 have divergent effects
      on PSA expressions. The effects of LXR agonists on PSA expression are LXRalpha
      dependent and AR-dependent. EGCG blocks the inducing effect of GW3965 on PSA
      expression.

PMID- 25560460
TI  - Enantioselective syntheses and sensory properties of 2-methyl-tetrahydrofuran-3
      thiol acetates.
AB  - The enantioselective synthesis of four stereoisomers of 2-methyl-tetrahydrofuran
      3-thiol acetate was achieved. The two enantiomers of the important intermediate
      cis-2-methyl-3-hydroxy-tetrahydrofuran were obtained by Sharpless asymmetric
      dihydroxylation (AD), whereas the two enantiomers of trans-2-methyl-3-hydroxy
      tetrahydrofuran were derived from the corresponding optically active cis-isomers
      by Mitsunobu reaction. Each stereoisomer of 2-methyl-3-hydroxy-tetrahydrofuran
      went through mesylation and nucleophilic substitution to afford the corresponding
      product with specific configuration. (2R,3S)- and (2R,3R)-2-methyl
      tetrahydrofuran-3-thiol acetate were obtained in 80% ee, whereas the (2S,3R)- and
      (2S,3S)-isomers were in 62% ee. The odor properties of the synthesized four
      stereoisomers were evaluated by gas chromatography-olfactometry (GC-O), which
      revealed perceptible differences among stereoisomers both in odor features and in
      intensities. 

PMID- 25560462
TI  - Intronic and promoter polymorphisms of hMLH1/hMSH2 and colorectal cancer risk in
      Heilongjiang Province of China.
AB  - PURPOSE: Given that mismatch repair (MMR) system plays an important role in
      recognizing and removing insertion/deletion mutations which occur during DNA
      replication, common variants associated with impaired MMR system may thus
      increase risk of colorectal cancer (CRC). Therefore, we aimed to demonstrate the
      associations between common variants in two MMR genes (hMLH1 and hMSH2) and CRC
      risk. METHODS: We genotyped 10 intronic/promoter single-nucleotide polymorphisms
      (SNPs) of hMLH1 and hMSH2 in 451 CRC patients and 630 controls. Associations
      between genotypes and CRC risk were estimated using odds ratios and 95 %
      confidence intervals. Gene-gene interactions, as well as gene-environment
      interactions on CRC risk were also investigated. RESULTS: We found that IVS15
      214T>C and IVS11 + 107A>G of hMSH2 were significantly associated with CRC risk.
      In dominant model, variant carriers of the two SNPs could decrease risk of CRC by
      31 % (ORadj = 0.69, 95 % CI 0.53-0.91, p < 0.01) and 33 % (ORadj = 0.67, 95 % CI
      0.47-0.95, p = 0.02), respectively. In addition, IVS7-212T>A, IVS11+183A>G and
      IVS8+719T>C of hMSH2 were associated with the susceptibility to colon cancer
      rather than rectal cancer. ATTTGGGT and TCTTAGAC haplotypes were associated with
      44 and 45 % decreased risk of CRC, respectively, while ATTTGAGT and TTTCAGAC
      haplotypes were associated with 1.37-fold and 2.49-fold increased risk of CRC,
      respectively. There was a significant three-way gene-gene interaction among hMSH2
      IVS11+107A>G, IVS11+183A>G and IVS8+719T>C (p < 0.01). Significant gene
      environment interactions were observed between hMSH2 IVS15-214T>C and
      IVS11+107A>G and cereals consumption (both with p < 0.01). CONCLUSIONS: Our
      findings suggested that intronic SNPs, gene-gene and gene-environment
      interactions in hMSH2 might be associated with susceptibility to CRC.

PMID- 25560463
TI  - Entecavir allows an unexpectedly high residual replication of HBV mutants
      resistant to lamivudine.
AB  - BACKGROUND: Entecavir is an efficient inhibitor of HBV reverse transcriptase (RT)
      and widely used for therapy of chronic hepatitis B. Entecavir treatment of HBV
      patients with lamivudine-resistant viral strains, however, often fails, but the
      mechanism of cross-resistance development is not fully understood. METHODS: Using
      non-linear regression models, dose-response curves of cloned HBV strains from
      patients pre-treated with RT inhibitors were established in human hepatoma cell
      lines after transfection with HBV genomes containing HBV polymerase genes from
      patient isolates. 50% and 90% inhibitory concentrations (IC50 and IC90) and
      corresponding antiviral resistance factors (RF50 and RF90) were calculated.
      RESULTS: The entecavir dose-response curve of lamivudine-resistant HBV RT mutants
      rtM204 for the replication of HBV decreased less than expected with increasing
      drug dose. Remarkably, due to the flat dose-response curves, RF90 values against
      entecavir of samples with rtM204 substitutions were up to 30* higher than their
      RF50 values. CONCLUSIONS: The unexpectedly high IC90 indicates a strong residual
      replication capacity of lamivudine-resistant HBV rtM204 variants under entecavir
      therapy, although IC50 values are initially within the therapeutic range of
      entecavir. This characteristic favours rapid selection of additional mutants with
      overt resistance against entecavir. Thus, the current phenotypic resistance
      assays should include determination of IC90.

PMID- 25560464
TI  - Community perspectives on drug/alcohol use, concerns, needs, and resources in
      four Washington State Tribal communities.
AB  - Community-university teams investigated substance use, abuse, and dependence
      (SUAD) and related concerns, needs, strengths, and resources in four Washington
      State Tribal communities. A total of 153 key community members shared their
      perspectives through 43 semi-structured interviews and 19 semi-structured focus
      groups. Qualitative data analysis revealed robust themes: prescription
      medications and alcohol were perceived as most prevalent and concerning; family
      and peer influences and emotional distress were prominent perceived risk factors;
      and SUAD intervention resources varied across communities. Findings may guide
      future research and the development of much needed strength-based, culturally
      appropriate, and effective SUAD interventions for American Indians, Alaska
      Natives, and their communities. 

PMID- 25560465
TI  - Antispasmodic effect of Ocimum selloi essential oil on the guinea-pig ileum.
AB  - Ocimum selloi is an herbal species popularly used in Brazil as antispasmodic.
      Herein, we report the antispasmodic effect of O. selloi essential oil (OS) in
      segments of guinea-pig ileum. OS did not reduce the tonus of the ileum. In
      contrast, OS reduced the contraction induced by carbachol (100 MUM), BaCl2 (0.03
      M) and low- and high-K(+) concentrations (25 and 60 mM, respectively). OS shifted
      the concentration-response curve for calcium to the right in a parallel manner.
      GC/MS analysis showed that OS consists mostly of methyl chavicol (97.57%). These
      results suggest that OS antispasmodic effect is mediated through calcium channel
      blockade. In addition, OS effect and mode of action could be accounted for methyl
      chavicol.

PMID- 25560461
TI  - Efferent innervation of turtle semicircular canal cristae: comparisons with bird
      and mouse.
AB  - In the vestibular periphery of nearly every vertebrate, cholinergic vestibular
      efferent neurons give rise to numerous presynaptic varicosities that target hair
      cells and afferent processes in the sensory neuroepithelium. Although
      pharmacological studies have described the postsynaptic actions of vestibular
      efferent stimulation in several species, characterization of efferent innervation
      patterns and the relative distribution of efferent varicosities among hair cells
      and afferents are also integral to understanding how efferent synapses operate.
      Vestibular efferent markers, however, have not been well characterized in the
      turtle, one of the animal models used by our laboratory. Here we sought to
      identify reliable efferent neuronal markers in the vestibular periphery of
      turtle, to use these markers to understand how efferent synapses are organized,
      and to compare efferent neuronal labeling patterns in turtle with two other
      amniotes using some of the same markers. Efferent fibers and varicosities were
      visualized in the semicircular canal of red-eared turtles (Trachemys scripta
      elegans), zebra finches (Taeniopygia guttata), and mice (Mus musculus) utilizing
      fluorescent immunohistochemistry with antibodies against choline
      acetyltransferase (ChAT). Vestibular hair cells and afferents were counterstained
      using antibodies to myosin VIIa and calretinin. In all species, ChAT labeled a
      population of small diameter fibers giving rise to numerous spherical
      varicosities abutting type II hair cells and afferent processes. That these ChAT
      positive varicosities represent presynaptic release sites were demonstrated by
      colabeling with antibodies against the synaptic vesicle proteins synapsin I, SV2,
      or syntaxin and the neuropeptide calcitonin gene-related peptide. Comparisons of
      efferent innervation patterns among the three species are discussed.

PMID- 25560466
TI  - Next in line in next-generation sequencing: are we there yet?

PMID- 25560467
TI  - Investigation of TSPO variants in schizophrenia and antipsychotic treatment
      outcomes.
AB  - AIM: TSPO is a neuroinflammatory biomarker and emerging therapeutic target in
      psychiatric disorders. We evaluated whether TSPO polymorphisms contribute to
      interindividual variability in schizophrenia, antipsychotic efficacy and
      antipsychotic-induced weight gain. PATIENTS & METHODS: We analyzed TSPO
      polymorphisms in 670 schizophrenia cases and 775 healthy controls. Gene-gene
      interactions between TSPO and other mitochondrial membrane protein-encoding genes
      (VDAC1 and ANT1) were explored. Positive findings were evaluated in two
      independent samples (Munich, n = 300; RUPP, n = 119). RESULTS: TSPO rs6971 was
      independently associated with antipsychotic-induced weight gain in the discovery
      (puncor = 0.04) and RUPP samples (p = 3.00 * 10(-3)), and interacted with ANT1
      rs10024068 in the discovery (p = 1.15 * 10(-3)) and RUPP samples (p = 2.76 * 10(
      4)). CONCLUSION: Our findings highlight TSPO as a candidate for future
      investigations of antipsychotic-induced weight gain, and support the involvement
      of mitochondrial membrane components in this serious treatment side effect.

PMID- 25560468
TI  - Predicting chemosensitivity to gemcitabine and cisplatin based on gene
      polymorphisms and mRNA expression in non-small-cell lung cancer cells.
AB  - AIM: We used a panel of 17 non-small-cell lung cancer cell lines to investigate
      whether the presence of polymorphisms in the RRM1, ERCC1, ABCB1 and MTHFR genes
      and alterations in their mRNA expression can affect the in vitro chemosensitivity
      to cisplatin and gemcitabine. MATERIALS & METHODS: Polymorphisms in these genes
      were evaluated by direct sequencing. mRNA expression levels were assessed by
      realtime PCR. In vitro chemosensitivity to cisplatin and gemcitabine was
      expressed as IC50 values, using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) assay. RESULTS: There was a significant, positive
      correlation between RRM1 mRNA expression and IC50 values for gemcitabine (r =
      0.6533, p = 0.0045), and there was a significant, negative correlation between
      ABCB1 mRNA expression and IC50 values for cisplatin (r = -0.5459, p = 0.0287).
      When examining the association between the polymorphisms and IC50, we found that
      only the MTHFR 1298A>C polymorphism showed a tendency to be more chemosensitive
      to gemcitabine (p = 0.0440). CONCLUSION: These in vitro results suggest that mRNA
      expression levels of the RRM1 and ABCB1 genes may be useful indicators of
      chemosensitivity to gemcitabine and cisplatin, respectively. The MTHFR 1298A>C
      polymorphism was associated with gemcitabine chemosensitivity, which require
      further functional analysis with co-expressed genes and should be explored in
      prospective clinical studies to determine its potential clinical application as a
      predictive biomarker. Original submitted 11 February 2014; Revision submitted 3
      November 2014.

PMID- 25560469
TI  - COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: effects on the negative
      symptom response to clozapine.
AB  - AIM: Clozapine is still considered the gold standard for treatment-resistant
      schizophrenia patients; however, up to 40% of patients do not respond adequately.
      Identifying potential predictors of clinical response to this last-line
      antipsychotic could represent an important goal for treatment. Among these,
      functional polymorphisms involved in dopamine system modulation, known to be
      disrupted in schizophrenia, may play a role. We examined the COMT Val158Met
      polymorphism, which plays a key role in dopamine regulation at the prefrontal
      level, and the 5-HT1A-R -1019 C/G polymorphism, a target of clozapine activity
      involved in the interaction between the serotonin and dopamine systems. MATERIALS
      & METHODS: 107 neuroleptic-refractory, biologically unrelated Italian patients
      (70 males and 37 females) with a DSM-IV diagnosis of schizophrenia who were being
      treated with clozapine were recruited. Psychopathology was assessed by the
      Positive and Negative Symptoms Scale (PANSS) at the beginning of treatment, and
      at weeks 8 and 12. Genomic DNA was extracted from venous blood samples. COMT
      rs4680 (Val158Met) and 5-HT1A-R rs6295 (-1019 C/G) polymorphisms were analyzed by
      PCR-based restriction fragment length and direct sequencing, respectively.
      RESULTS: We found a significant effect of COMT and 5-HT1A-R on the PANSS Negative
      Subscale variation, with greater improvement among COMT Val/Val and 5-HT1A-R G/G
      subjects. CONCLUSION: The findings support the hypothesis that COMT rs4680 and 5
      HT1A-R rs6295 polymorphisms could influence the negative symptom response to
      clozapine, probably through modulation of the dopaminergic system.

PMID- 25560470
TI  - Pharmacogenomics of glinides.
AB  - Glinides, including repaglinide, nateglinide and mitiglinide, are a type of
      fasting insulin secretagogue that could help to mimic early-phase insulin
      release, thus providing improved control of the postprandial glucose levels.
      Glinides stimulate insulin secretion by inhibiting ATP-sensitive potassium
      channels in the pancreatic beta-cell membrane. Although glinides have been widely
      used clinically and display excellent safety and efficacy, the response to
      glinides varies among individuals, which is partially due to genetic factors
      involved in drug absorption, distribution, metabolism and targeting. Several
      pharmacogenomic studies have demonstrated that variants of genes involved in the
      pharmacokinetics or pharmacodynamics of glinides are associated with the drug
      response. Polymorphisms of genes involved in drug metabolism, such as CYP2C9,
      CYP2C8 and SLCO1B1, may influence the efficacy of glinides and the incidence of
      adverse effects. In addition, Type 2 diabetes mellitus susceptibility genes, such
      as KCNQ1, PAX4 and BETA2, also influence the efficacy of glinides. In this
      article, we review and discuss current pharmacogenomics researches on glinides,
      and hopefully provide useful data and proof for clinical application. 

PMID- 25560471
TI  - Impact of VEGF gene polymorphisms in elderly cancer patients: clinical outcome
      and toxicity.
AB  - Vascular endothelial growth factors (VEGFs) are the key regulators in
      angiogenesis and have been shown to play a significant role in the progression
      and prognosis of angiogenesis-related diseases, such as cancer. VEGF inhibitors
      are a current pharmacological tumoral strategy. However, despite the strong
      association between aging and cancer incidence and progression, recent findings
      suggest impaired angiogenesis accompanied by a reduced expression of VEGF in
      cells derived from aging subjects. Specific variations of VEGF genes have been
      demonstrated to be genetic determinants for susceptibility, outcome and therapy
      response, especially for the solid tumors. Considering the complications present
      in frail elderly patients, analysis of VEGF genetic polymorphisms in these
      subjects may further help in tailoring an angiogenic pharmacological strategy,
      and in improving our ability to better understand prognosis during therapy
      related to cancer. 

PMID- 25560472
TI  - Prognostic and predictive role of vascular endothelial growth factor
      polymorphisms in breast cancer.
AB  - Current evidence indicates that angiogenesis plays an important role in the
      pathogenesis of several malignancies, including breast cancer. The vascular
      endothelial growth factor (VEGF) pathway has been investigated extensively, due
      to its important role in angiogenesis. The major mediator of tumor angiogenesis
      is VEGF-A, frequently referred to as VEGF, which activates the VEGF receptor-2.
      The VEGF gene is located on chromosome 6 and constitutes a highly polymorphic
      gene. Numerous SNPs in the promoter, 5'- and 3'-untranslated regions (UTR) of
      VEGF gene have been recognized. This genetic variability possibly influences the
      production and function of VEGF. Subsequently, the VEGF SNPs may have an impact
      on breast cancer risk and disease outcome. Moreover, these SNPs may be of
      predictive value in patients receiving agents targeting the VEGF pathway. This
      review presents an update on the potential role of VEGF SNPs as prognostic and/or
      predictive markers in patients with breast cancer. 

PMID- 25560473
TI  - Modulation of alternative splicing with chemical compounds in new therapeutics
      for human diseases.
AB  - Alternative splicing is a critical step where a limited number of human genes
      generate a complex and diverse proteome. Various diseases, including inherited
      diseases with abnormalities in the "genome code," have been found to result in an
      aberrant mis-spliced "transcript code" with correlation to the resulting
      phenotype. Chemical compound-based and nucleic acid-based strategies are trying
      to target this mis-spliced "transcript code". We will briefly mention about how
      to obtain splicing-modifying-compounds by high-throughput screening and overview
      of what is known about compounds that modify splicing pathways. The main focus
      will be on RNA-binding protein kinase inhibitors. In the main text, we will refer
      to diseases where splicing-modifying-compounds have been intensively
      investigated, with comparison to nucleic acid-based strategies. The information
      on their involvement in mis-splicing as well as nonsplicing events will be
      helpful in finding better compounds with less off-target effects for future
      implications in mis-splicing therapy. 

PMID- 25560474
TI  - Adenoviral vectors as novel vaccines for influenza.
AB  - OBJECTIVES: Influenza is a viral respiratory disease causing seasonal epidemics,
      with significant annual illness and mortality. Emerging viruses can pose a major
      pandemic threat if they acquire the capacity for sustained human-to-human
      transmission. Vaccination reduces influenza-associated mortality and is critical
      in minimising the burden on the healthcare system. However, current vaccines are
      not always effective in at-risk populations and fail to induce long-lasting
      protective immunity against a range of viruses. KEY FINDINGS: The development of
      'universal' influenza vaccines, which induce heterosubtypic immunity capable of
      reducing disease severity, limiting viral shedding or protecting against
      influenza subtypes with pandemic potential, has gained interest in the research
      community. To date, approaches have focused on inducing immune responses to
      conserved epitopes within the stem of haemagglutinin, targeting the ectodomain of
      influenza M2e or by stimulating cellular immunity to conserved internal antigens,
      nucleoprotein or matrix protein 1. SUMMARY: Adenoviral vectors are potent
      inducers of T-cell and antibody responses and have demonstrated safety in
      clinical applications, making them an excellent choice of vector for delivery of
      vaccine antigens. In order to circumvent pre-existing immunity in humans,
      serotypes from non-human primates have recently been investigated. We will
      discuss the pre-clinical development of these novel vectors and their advancement
      to clinical trials.

PMID- 25560476
TI  - The development of GADD45alpha luciferase reporter assays in human cells for
      assessing the genotoxicity of environmental pollutants.
AB  - OBJECTIVES: In order to assess the potential carcinogenic and genotoxic responses
      induced by environmental pollutants, genotoxicity test systems based on a
      GADD45alpha promoter-driven luciferase reporter in human A549 and HepG2 cells
      were established. MATERIALS AND METHODS: Four different types of environmental
      toxicants including DNA alkylating agents, precarcinogenic agents, DNA cross
      linking agents and non-carcinogenic agents, and three environmental samples
      collected from a coke oven plant were used to evaluate the test systems. After
      treated with the tested agents and environmental samples for 12 h, the cell
      viabilities and luciferase activities of the luciferase reporter cells were
      determined, respectively. RESULTS: Methyl methanesulfonate, benzo[a]pyrene,
      formaldehyde and the extractable organic matter (EOM) from coke oven emissions in
      ambient air generally produced significant induction of relative luciferase
      activity in a similar dose-dependent manner in A549- and HepG2-luciferase cells.
      No significant increases in relative luciferase activity were observed in pyrene
      treated A549- or HepG2-luciferase cells. Significant increase in relative
      luciferase activity was already evident after 2.5 uM benzo[a]pyrene, 5 uM
      formaldehyde, 0.006 ug/L bottom-EOM, 0.10 ug/L side-EOM or 0.06 ug/L top-EOM,
      where no cytotoxic damage was observed. Compared with the A549-luciferase cells,
      the tested pollutants produced higher induction of relative luciferase activity
      in HepG2-luciferase cells. DISCUSSION AND CONCLUSION: Therefore, the new
      genotoxicity test systems can detect different types of genotoxic agents and low
      concentrations of environmental samples. The luciferase reporter cells,
      especially the HepG2-luciferase cells, could provide a valuable tool for rapid
      screening of the genotoxic damage of environmental pollutants and their complex
      mixtures.

PMID- 25560475
TI  - Association of laryngeal and nasopharyngeal tuberculosis: a case report.
AB  - INTRODUCTION: To the best of our knowledge, the association of nasopharyngeal and
      laryngeal tuberculosis has never been described before in the literature. We
      report here a first observation. CASE PRESENTATION: We report the case of a 38
      year-old Arab man who presented with an isolated hoarseness. Radiological and
      endoscopic examinations showed a thickening of the left lateral wall of his
      nasopharynx and the left vocal cord. Pathology revealed the diagnosis of
      tuberculosis of both localizations. He received a 6-month antituberculous
      chemotherapy with a satisfying uneventful evolution. CONCLUSIONS: Tuberculosis
      should be considered in the differential diagnosis of soft tissue masses of the
      head and neck, particularly when the imaging findings and clinical presentation
      are atypical. The diagnosis of tuberculosis is mainly based on histopathological
      and/or bacteriological examination.

PMID- 25560477
TI  - The Shoulder Pain and Disability Index: Is it sensitive and responsive to
      immediate change?
AB  - BACKGROUND: The Shoulder Pain and Disability Index (SPADI) is designed to detect
      changes in shoulder pain and disability after a one-week interval. With the new
      Medicare guideline, the SPADI may have to be employed for time frames of less
      than one week. PURPOSE: To determine if the SPADI or its subscales could detect
      immediate changes in pain and function after a thoracic manipulative intervention
      known to produce short-term improvement and by comparing it to changes on the
      numeric pain rating scale (NPRS). METHODS: Subjects with primary complaints of
      non-post-surgical shoulder pain completed the NPRS and the SPADI prior to and
      immediately following interventions. FINDINGS: The SPADI pain subscale detected
      statistically significant differences that were also detected using the NPRS. In
      addition, the SPADI pain score and the NPRS scores were moderately correlated
      between the pre-intervention SPADI and NPRS scores (r = 0.49-0.61, p < 0.001) and
      post-intervention SPADI and NPRS scores (r = 0.49-0.67, p < 0.001). These
      differences did not appear to be sensitive or responsive to immediate change.
      CLINICAL RELEVANCE: Since the SPADI may have to be employed in durations of less
      than one week secondary to third party payer requirements, it is valuable to
      validate the SPADI for this particular use. CONCLUSION: Although SPADI scores
      demonstrated low sensitivity and responsiveness to immediate changes, the SPADI
      pain scale was able to detect changes in durations of less than one week. This
      finding should be confirmed through further prospective experimentation.

PMID- 25560478
TI  - Early UCSF contributions to the development of multiple-channel cochlear
      implants.
AB  - The early contributions of the UCSF cochlear implant (CI) research team to the
      development of multiple-channel cochlear implants from about 1971 through the mid
      1980s are briefly summarized. Scientists at UCSF conducted fundamental studies
      related to device safety, the control of patterned electrical stimulation, and
      the designs of intracochlear electrode arrays, coders, and implanted multiple
      channel electrode drivers. They conducted many original studies documenting
      parameters of hearing with cochlear implants relevant to next-generation CI
      designs. On these bases, the UCSF team constructed early models of multichannel
      devices that were progenitors of the Advanced Bionics' Clarion CI. This article
      is part of a Special Issue entitled <Lasker Award>. 

PMID- 25560479
TI  - Relationship between the Rorschach Perceptual Thinking Index (PTI) and the
      Positive and Negative Syndrome Scale (PANSS) in psychotic patients: a validity
      study.
AB  - The aim of this study is to demonstrate the validity of the Rorschach Perceptual
      Thinking Index (PTI) in the assessment of reality testing in patients with
      psychosis. We evaluated the relationship between the PTI criteria and the
      Positive and Negative Syndrome Scale (PANSS) scores in 98 psychotic disorder
      affected patients. Thirty four were evaluated during the acute episode (AP) and
      64 were chronically treated and stable (CP). The PANSS positive score resulted
      significantly higher in AP than in CP group, but no significant difference was
      found in the PTI score. The PTI positively correlated with the PANSS total score.
      The PTI1 and PTI2 criteria significantly correlated with the PANSS negative
      score, the PTI4 and PTI5 with the positive. The Rorschach variable X-%
      significantly correlated with the negative symptoms; the WSum6 with thought
      disorders; and the M- with delusions. PTI score, X-% and WSum6 predicted impaired
      judgment and insight. These results suggest that PTI is a valid instrument to
      assess impairment in reality testing, regardless of the patient's current
      psychiatric presentation. The presence of conceptual disorganization, delusions,
      lack of judgment and insight don't have effects on the PTI, supporting its
      strength as an assessment tool for psychotic disorders. 

PMID- 25560480
TI  - A systematic review of treatments for Impulse Control Disorders and related
      behaviours in Parkinson's disease.
AB  - Impulse Control Disorders (ICDs) are a set of behaviours characterised by
      impulsivity despite known harm. Related to ICDs is the dopamine dysregulation
      syndrome (DDS), which is characterised by an addiction-like consumption of
      dopaminergic medication and punding. These behaviours all have an increased
      prevalence in Parkinson's disease (PD). The aim of this review is to identify
      treatments available for patients suffering from ICDs, DDS and punding in PD.
      Searches of The Cochrane Controlled Trials Register, Embase, Medline and
      PsychInfo were conducted, using the entire timescale available. Seven out of the
      688 papers retrieved met the inclusion criteria and were considered in this
      systematic review. One class I study, one class II study, and five class IV
      studies were identified. All studies demonstrated a positive effect on ICDs in
      PD. Research in this field is still in its early stages. At present, there is
      insufficient evidence to recommend any treatment over another. There is a need
      for more methodologically robust research, using larger, more generalisable
      samples, randomisation and meaningful follow-up periods. In addition, the use of
      a validated outcome measures should be implemented in future research efforts. 

PMID- 25560481
TI  - Temperament and character as predictors of recurrence in remitted patients with
      major depression: a 4-year prospective follow-up study.
AB  - The aim of the present study was to examine whether the specific personality
      traits, Harm-Avoidance (HA) and Self-Directedness (SD) as measured by the
      Temperament and Character Inventory (TCI), were predictive for subsequent
      depressive episodes in remitted patients with major depressive disorders (MDDs)
      over a 4-year follow-up. A total of 109 inpatients with MDD participated in this
      study. The subjects completed the TCI when they were assessed to be in remission.
      They were divided into high or low HA groups and high or low SD groups, as
      discriminated by the quartile value. A total of 69 patients were followed-up over
      a 4-year period or until recurrence. Both Kaplan-Meier analysis and Cox's
      proportional hazards regression analysis indicated that patients with a low SD
      score had a significantly shorter time to recurrence from remission than patients
      with a high SD score even when some prognostic predictors were controlled for. In
      contrast, HA was not found to be a predictor of recurrence for future depressive
      episodes. A part of MDD patients with low scores in Self-Directedness are likely
      to develop depression over a subsequent period of time. Interventions that
      improve SD may help to delay recurrence of depression in MDD patients. 

PMID- 25560482
TI  - Right ventricular echocardiographic parameters are associated with mortality
      after acute pulmonary embolism.
AB  - BACKGROUND: There is limited information on the utility of certain
      echocardiographic measurements, such as right ventricular (RV) strain analysis,
      in predicting mortality in patients with acute pulmonary embolism (PE). METHODS:
      A total of 211 patients with acute PE admitted to a medical intensive care unit
      (ICU) were retrospectively identified. Echocardiographic variables were
      prospectively measured in this cohort. The focus was on ICU, hospital, and long
      term mortality. RESULTS: The mean age was 61 +/- 15 years. Median Acute
      Physiology and Chronic Health Evaluation IV and simplified Pulmonary Embolism
      Severity Index scores were 60 (interquartile range, 40-71) and 2 (interquartile
      range, 1-2), respectively. Thirty-eight patients (18%) died during the sentinel
      hospitalization (13% died in the ICU). A total of 61 patients (28.9%) died during
      a median follow-up period of 15 months (interquartile range, 5-26 months). The
      echocardiographic variables associated with long-term mortality (from PE
      diagnosis) were ratio of RV to left ventricular end-diastolic diameter (hazard
      ratio [HR], 2.4; 95% confidence interval [CI], 1.2-4.8), tricuspid annular plane
      systolic excursion (HR, 0.53; 95% CI, 0.31-0.92), and RV-right atrial gradient
      (HR, 1.02; 95% CI, 1.01-1.4). ICU mortality was associated with ratio of RV to LV
      end-diastolic diameter (HR, 4.4; 95% CI, 1.3-15), RV systolic pressure (HR, 1.03;
      95% CI, 1.01-1.05), tricuspid annular plane systolic excursion (HR, 0.4; 95% CI,
      0.18-0.9), and inferior vena cava collapsibility < 50% (HR, 4.3; 95% CI, 1.7-11).
      These variables remain significantly associated with mortality after adjusting by
      Acute Physiology and Chronic Health Evaluation IV score, Pulmonary Embolism
      Severity Index score, or the use of thrombolytic agents. RV strain parameters
      were not correlated with hospital or long-term mortality. CONCLUSIONS: Four
      simple parameters that measure different aspects of the right ventricle (ratio of
      RV to left ventricular end-diastolic diameter, RV systolic pressure, tricuspid
      annular plane systolic excursion, and inferior vena cava collapsibility) were
      independently associated with mortality in patients presenting with acute PE who
      were admitted to the ICU.

PMID- 25560483
TI  - Impact of device landing zone calcification on paravalvular regurgitation after
      transcatheter aortic valve replacement: a real-time three-dimensional
      transesophageal echocardiographic study.
AB  - BACKGROUND: Determinants of paravalvular regurgitation after transcatheter aortic
      valve replacement (TAVR) remain unclear. The purpose of this study was to
      investigate the impact of aortic valve calcification (AVC) on paravalvular
      regurgitation after TAVR using real-time three-dimensional transesophageal
      echocardiography. METHODS: A total of 227 patients with severe aortic stenosis
      who underwent TAVR using the Edwards SAPIEN or SAPIEN XT valve were
      retrospectively analyzed. Severity of AVC was assessed on a visual scale ranging
      from 0 to 3 at the aortic annulus, the leaflets near the nadir, and the
      commissure. The shape of calcification was assessed by measuring the radial and
      circumferential lengths of annular calcification and by focusing on the
      calcification protruding into the left ventricular outflow tract from the annular
      level. Severity of paravalvular regurgitation was determined by the sum of the
      cross-sectional area of the vena contracta from two-dimensional or three
      dimensional color Doppler transesophageal echocardiographic data. Significant
      paravalvular regurgitation was defined as at least a moderate grade. RESULTS:
      After excluding 25 patients with inadequate image quality of three-dimensional
      and color Doppler data for analysis, AVC could be evaluated in 202 patients.
      Significant paravalvular regurgitation was occurred in 37 patients (18%). The sum
      of the AVC scale at the annulus was significantly correlated with the grade of
      paravalvular regurgitation, while those at the leaflets near the nadir and the
      commissure were not. As assessed by receiver operating characteristic curve
      analysis, the radial and circumferential length of the annular calcification had
      good discriminatory ability for significant paravalvular regurgitation, with
      areas under the curve of 0.91 and 0.81, respectively. On multivariate analysis,
      annular calcification with radial length >= 3.0 mm, circumferential length >= 8.0
      mm, and calcification protruding into the left ventricular outflow tract were
      independently associated with significant paravalvular regurgitation.
      CONCLUSIONS: Assessment of AVC by real-time three-dimensional transesophageal
      echocardiography is feasible and has good discriminatory value for paravalvular
      regurgitation in patients who undergo TAVR. Significant paravalvular
      regurgitation after TAVR is associated with the location and size of
      calcification at the aortic annulus and left ventricular outflow tract, not with
      its severity.

PMID- 25560484
TI  - Right heart mechanics in untreated normotensive patients with prediabetes and
      type 2 diabetes mellitus: a two- and three-dimensional echocardiographic study.
AB  - BACKGROUND: The aim of this study was to determine right ventricular (RV) and
      right atrial (RA) deformation assessed by two-dimensional echocardiographic and
      three-dimensional echocardiographic (3DE) imaging in patients with prediabetes
      and type 2 diabetes mellitus. METHODS: This cross-sectional study included 47
      untreated normotensive subjects with prediabetes, 57 recently diagnosed
      normotensive patients with diabetes, and 54 healthy controls of similar sex and
      age distributions. All subjects underwent laboratory analyses and complete two
      dimensional echocardiographic and 3DE examinations. RESULTS: Three-dimensional
      echocardiographic RV end-diastolic volume index gradually decreased from controls
      across patients with diabetes to those with diabetes (69 +/- 10 vs 63 +/- 8 vs 58
      +/- 8 mL/m(2), P < .001), whereas 3DE RV end-systolic volume index was higher in
      controls compared with patients with diabetes and those with diabetes (25 +/- 4
      vs 23 +/- 4 vs 22 +/- 4 mL/m(2), P < .001). However, there was no difference in
      3DE RV ejection fraction among the three groups (63 +/- 4% vs 62 +/- 4% vs 61 +/-
      5%, P = .063). RV and RA global strain and systolic and early diastolic strain
      rates were decreased in patients with prediabetes and in those with diabetes
      compared with controls, whereas RV and RA late diastolic strain rates were
      increased in these patients. Multivariate regression analysis showed that RV
      global strain was associated with glycated hemoglobin, independent of left
      ventricular parameters. CONCLUSIONS: RV and RA myocardial deformation and
      function obtained by 3DE and two-dimensional echocardiographic strain, even in
      normal ranges, were decreased in patients with prediabetes and in those with
      diabetes compared with controls. The long-term parameter of glucose control was
      correlated with the right heart mechanics.

PMID- 25560486
TI  - Intestinal steroidogenesis.
AB  - Steroids are fundamental hormones that control a wide variety of physiological
      processes such as metabolism, immune functions, and sexual characteristics.
      Historically, steroid synthesis was considered a function restricted to the
      adrenals and the gonads. In the past 20 years, a significant number of studies
      have demonstrated that steroids could also be synthesized or metabolized by other
      organs. According to these studies, the intestine appears to be a major source of
      de novo produced glucocorticoids as well as a tissue capable of producing and
      metabolizing sex steroids. This finding is based on the detection of
      steroidogenic enzyme expression as well as the presence of bioactive steroids in
      both the rodent and human gut. Within the intestinal mucosa, the intestinal
      epithelial cell layer is one of the main cellular sources of steroids.
      Glucocorticoid synthesis regulation in the intestinal epithelial cells is unique
      in that it does not involve the classical positive regulator steroidogenic factor
      1 (SF-1) but a closely related homolog, namely the liver receptor homolog-1 (LRH
      1). This local production of immunoregulatory glucocorticoids contributes to
      intestinal homeostasis and has been linked to pathophysiology of inflammatory
      bowel diseases. Intestinal epithelial cells also possess the ability to
      metabolize sex steroids, notably estrogen; this mechanism may impact colorectal
      cancer development. In this review, we contextualize and discuss what is known
      about intestinal steroidogenesis and regulation as well as the key role these
      functions play both in physiological and pathological conditions.

PMID- 25560485
TI  - CYP17A1 inhibitors in castration-resistant prostate cancer.
AB  - The majority of prostate cancer (PCa) cases are diagnosed as a localized disease.
      Definitive treatment, active surveillance or watchful waiting are employed as
      therapeutic paradigms. The current standard of care for the treatment of
      metastatic PCa is either medical or surgical castration. Once PCa progresses in
      spite of castrate androgen levels it is termed 'castration-resistant prostate
      cancer' (CRPC). Patients may even exhibit rising PSA levels with possible bone,
      lymph node or solid organ metastases. In 2010, the only agent approved for the
      treatment of CRPC was docetaxel, a chemotherapeutic agent. It is now known that
      cells from patients with CRPC express androgen receptors (AR) and remain
      continuously influenced by androgens. As such, treatments with novel hormonal
      agents that specifically target the biochemical conversion of cholesterol to
      testosterone have come to the forefront. The use of cytochrome P450c17 (CYP17A1)
      inhibitor underlies one of the most recent advances in the treatment of CRPC.
      Abiraterone acetate (AA) was the first CYP17A1 inhibitor approved in the United
      States. This review will discuss CRPC in general with a specific focus on AA and
      novel CYP17A1 inhibitors. AA clinical trials will be reviewed along with other
      novel adjunct treatments that may enhance the effectiveness of abiraterone
      therapy. Furthermore, the most recently identified CYP17A1 inhibitors Orteronel,
      Galeterone, VT-464, and CFG920 will also be explored. 

PMID- 25560487
TI  - CIP2A mediates prostate cancer progression via the c-MYC signaling pathway.
AB  - Recent evidence suggests that cancerous inhibitor of protein phosphatase 2A
      (CIP2A) is an oncoprotein that acts as a novel therapeutic target in a variety of
      tumors. In this study, we investigated the clinical significance of CIP2A and its
      function in our large collection of prostate samples. Between August 2000 and
      December 2013, 126 patients with histologically confirmed PCa and 92 with benign
      prostate hyperplasia (BPH) were recruited into the study. Quantitative RT-PCR,
      Western blot, and immunohistochemistry analyses were used to quantify CIP2A
      expression in PCa clinical samples and cell lines. The relationships between
      CIP2A expression and clinicopathological features were analyzed. The functional
      role of CIP2A in PCa cells was evaluated by small interfering RNA-mediated
      depletion of the protein followed by analyses of cell proliferation and invasion.
      High expression of CIP2A staining was 86.51 % (109/126) in 126 cases of PCa and
      17.39 % (16/92) in 92 cases of BPH, and the difference of CIP2A expression
      between PCa and BPH was statistically significant. CIP2A was significantly
      elevated in all five PCa cell lines when compared to the RWPE-1 cells at both the
      messenger RNA (mRNA) and protein levels. Silencing of CIP2A inhibited the
      proliferation of DU-145 cells which have a relatively high level of CIP2A in a
      time- and concentration-dependent manner, and the invasion and migration of DU
      145 cells were distinctly suppressed. Furthermore, CIP2A knockdown led to
      substantial reductions in c-Myc levels in PCa cell lines, but no significant
      change in phosphorylated Akt expression after CIP2A knockdown in DU-145 cells.
      Our data suggest that the pathogenesis of human PCa maybe mediated by CIP2A, and
      CIP2A inhibition treatment may provide a promising strategy for the antitumor
      therapy of PCa, and thus CIP2A could represent selective targets for the
      molecularly targeted treatments of PCa.

PMID- 25560488
TI  - MAPK inhibitors differently modulate TGF-beta/Smad signaling in HepG2 cells.
AB  - The aim of this study was to investigate the mitogen-activated protein kinase
      (MAPK) pathway, which crosstalk with TGF-beta/Smad signaling via linker
      phosphorylation of Smad2/3 to promote hepatocarcinogenesis. After DEN-induced
      hepatocellular carcinoma (HCC) in rats showed increased phosphorylation of
      JNK1/2, p38, and ERK1/2, we next antagonized TGF-beta1-induced phosphorylation of
      JNK1/2, p38, ERK1/2, Smad2/3 signaling in HepG2 cells using SP600125, SB203580,
      and PD98059, respectively. Cell proliferation and invasion were assessed by MTT
      assay and transwell invasion chambers, respectively. Smad2/3, Smad4, and Smad7
      expressions and PAI-1 messenger RNA (mRNA) transcription were measured by using
      immuno-precipitation/immuno-blotting and real-time RT-PCR, respectively. All the
      MAPK-specific inhibitors suppressed cell invasion, while all but PD98059
      suppressed cell proliferation. Both SP600125 and SB203580 blocked pSmad2C/L and
      oncogenic pSmad3L. PD98059 blocked pSmad2L but had no effect on elevated pSmad2C
      and oncogenic pSmad3L. All but PD98059 blocked Smad2/3/4 complex formation and
      restored Smad7 expression, while all the three MAPK-Specific inhibitors repressed
      PAI-1 mRNA transcription. Both SP600125 and SB203580 inhibited HepG2 cells'
      proliferation and invasion by blocking oncogenic pSmad3L and Smad2/3/4 complex
      formation. PD98059 repressed PAI-1 mRNA by an unknown mechanism. 

PMID- 25560489
TI  - p21-Activated kinase 5 affects cisplatin-induced apoptosis and proliferation in
      hepatocellular carcinoma cells.
AB  - p21-Activated kinase 5 (PAK5) is the last identified member of the PAK family.
      The PAKs are highly conserved serine/threonine and effector proteins for Cdc42
      and Rac and are essential in regulating cell motility and survival. Previous
      studies have demonstrated that PAK5 played a pivotal role in apoptosis,
      proliferation, cancer migration, and invasion. However, the biological function
      of PAK5 in hepatocellular carcinoma, as well as its underlying mechanism, still
      remains to be fully elucidated. In the present study, we demonstrated that PAK5
      markedly inhibited cisplatin-induced apoptosis and promoted cell proliferation in
      hepatocellular carcinoma cells. Moreover, our results showed that overexpression
      of PAK5 contributed to cell cycle regulation. In order to elucidate the
      underlying mechanism of PAK5 on cisplatin-induced apoptosis and cell cycle
      regulation, we also examined the protein expressions of chk2 and p-chk2. In
      summary, our study investigated the role of PAK5 in cisplatin-induced cellular
      processes and provided evidence of its underlying mechanism. 

PMID- 25560490
TI  - Downregulation of microRNA-145 is associated with aggressive progression and poor
      prognosis in human cervical cancer.
AB  - MicroRNAs (miRNAs) play important roles in the processes of tumor initiation and
      progression. However, miR-145 expression in cervical cancer has been rarely
      investigated. The aim of this study was to investigate the clinical significance
      and prognostic value of miR-145 expression in cervical cancer. MiR-145 expression
      in 114 pairs of human cervical cancer and adjacent normal tissues was detected by
      real-time quantitative RT-PCR assay. The results showed that miR-145 expression
      was significantly downregulated in cervical cancer tissues when compared with
      corresponding adjacent normal tissues (P < 0.001). It was also significantly
      lower in the cancerous tissues of patients with advanced International Federation
      of Gynecology and Obstetrics (FIGO) stage cervical cancer than those with early
      FIGO stage (P = 0.006). In addition, miR-145 was expressed at significantly lower
      levels in lymph node metastasis-positive patients than in lymph node metastasis
      negative patients (P = 0.037). Moreover, poorly differentiated tumors expressed
      lower miR-145 than well or moderately differentiated tumors (P = 0.012). Patients
      with vascular invasion or human papillomavirus (HPV) infection also had lower miR
      145 expression levels than those without (P = 0.016 and P = 0.025, respectively).
      Furthermore, Kaplan-Meier analysis showed that cervical cancer patients with low
      miR-145 expression had shorter overall survival time than those with high miR-145
      expression (P < 0.001). When analyzed with a multivariate Cox regression model,
      miR-145 was identified as an independent prognostic factor for overall survival.
      Taken together, our results suggest that downregulation of miR-145 in cervical
      cancer is associated with aggressive progression and poor prognosis and that miR
      145 may serve as a prognostic marker.

PMID- 25560492
TI  - Reversible degradation in ITO-containing organic photovoltaics under concentrated
      sunlight.
AB  - Stabilities of ITO-containing and ITO-free organic solar cells were investigated
      under simulated AM 1.5G illumination and under concentrated natural sunlight. In
      both cases ITO-free devices exhibit high stability, while devices containing ITO
      show degradation of their photovoltaic performance. The accelerated degradation
      under concentrated sunlight (of up to 20 suns) in ITO-containing devices was
      found to be reversible. Dark exposure of degraded samples can partly restore
      performance. A possible underlying mechanism for such a phenomenon is discussed. 

PMID- 25560491
TI  - Construction of a plasmid for overexpression of human circadian gene period2 and
      its biological activity in osteosarcoma cells.
AB  - Beyond their established role in the mammalian circadian clock, recent studies
      have confirmed that the circadian genes have been implicated in tumor onset and
      progression. Currently, the biological effects of circadian genes on osteosarcoma
      cells' proliferation and migration are not well understood. Period2 (Per2) is one
      of the core circadian genes that act as master regulators of development and is
      frequently dysregulated in several cancers. However, the effects of human Per2
      (hPer2) on the biological behavior of osteosarcoma cells are rarely reported. In
      the present study, to address the expression of hPer2 in osteosarcoma cells, the
      pEGFP-N1-hPer2 eukaryotic expression vector was constructed and transfected into
      cultured MG63 cells using LipofectamineTM 2000. The overexpression of hPer2 in
      MG63 cells was verified by qRT-PCR and Western blotting, respectively. Finally,
      we investigated the effects of hPer2 protein overexpression on MG63 cells'
      viability, cycle, apoptosis, and invasive ability. In conclusion, the recombinant
      pEGFP-N1-hPer2 plasmid had been constructed successfully and expressed
      effectively in MG63 cells. Furthermore, results also showed that the viability,
      proliferation, and invasive abilities were suppressed, and the apoptosis was
      enhanced in MG63 cells. This preliminary study provides ground work for further
      research on the roles of circadian gene hPer2 in osteosarcoma cells MG63 and
      would offer promise for the development of novel therapeutic strategies in the
      treatment of osteosarcoma. 

PMID- 25560493
TI  - Surgical treatment of gastric cancer in Japan, trend from standardization to
      individualization.
AB  - Japan has a huge number of patients with gastric cancer and has developed various
      surgical treatments for this disease.This paper intends to introduce our
      strategies against gastric cancer. The Japanese Gastric Cancer Association was
      established in 1962. Its major purposes are promotion of basic and clinical
      researches and popularization of the latest knowledge and technologies. For the
      purposes, the association organized the annual scientific meeting and the
      nationwide registry by member hospitals, and published the Japanese
      Classification of Gastric Cancer (1) and the Treatment Guide Line (2). The
      nationwide registry reported that proportion of Stage-I cancer was 22.5% in 1963
      66,which increased to 59.3% in 2008 (3,4,5). 11,261 patients with gastric
      resection were registered by 187 hospitals in 2008. 63 patients were died within
      30 postoperative days and the direct death rate was 0.55%. 5 year survival rate
      (5YSR) was 37.5% for resected cases in 1963-66, which was improved to 70.1% in
      2008. 5YSR was improved from 55.1% to 74.1% for Stage-II, and from 39.1% to 48.8%
      for Stage-III in the period. According to remarkable increase of early stage
      cancer, principle of surgical treatments was shifted from "??extended and
      standardized surgery for radicality" ??to "??reasonable and individual surgery
      considering safety and quality of life"??. This trend produced a large variation
      in surgical treatments; namely 1) minimally invasive surgeries,2) function
      preserving surgeries, 3) optimal extent of lymph node dissection, and 4)
      aggressive but safe surgeries.Intention of this paper is to explain these
      procedures, the intentions, the indications, and the treatment results.

PMID- 25560494
TI  - Splenic implant assessment in trauma.
AB  - Trauma is a global health issue, being the 4th death cause after cardio-vascular
      disease, malignancies and chronic pulmonary diseases and the main death cause
      among young people, under 45 years (1). The frequency of abdominal trauma is 10
      12% of all polytrauma, and from all abdominal organs, the spleen and liver are
      the most often involved in polytraumatized patients case (2). The first purpose
      of a successful operational management is the control of active bleeding, and the
      second is preserving as much as possible of the destroyed organs. Over the last
      decades, the treatment of spleen traumas had been diversified,from nonsurgical
      treatment to surgical, also complex and diversified: from conservative treatment
      to splenectomy.Currently, from a therapeutic standpoint, the trends in spleen
      trauma are orientated towards conservative methods as the clinical and
      experimental data have shown that ??it is better with the entire spleen than part
      of it, and better with a part of it than with none at all (Raymond Hinshaw) (3).

PMID- 25560495
TI  - Therapeutic strategies in colonic cancer.
AB  - Colonic cancer is the most common malignancy of the digestive tract, representing
      13% of all malignancies. The aim of the study is to evaluate the current
      therapeutic strategy in patients with CC. Mortality from the disease is declining
      in many Western countries; this may be the result of screening for CC, resection
      of adenomas, early detection of tumoral lesions and the use of individualized
      therapeutic strategies. The multimodal treatment of the disease includes
      different sequences such as: surgery, chemotherapy, radiotherapy,immunotherapy.
      Current advances in the research of mechanisms of carcinogenesis in CC make it
      possible to use genetic information in order to establish the prognostic and
      predictive factors for selecting the patients for individualized therapy. The
      current methods of CC evaluation allow the planning of individualized therapeutic
      strategies, which would lead to optimal results.

PMID- 25560496
TI  - Thyroid and thymic exeresis in surgery of hyperparathyroidism.
AB  - BACKGROUND: Owing to close anatomical and embryological connexions between the
      thyroid, parathyroids and thymus,manifold coexisting pathology can be identified
      during the surgery of hyperparathyroidism (Hp). MATERIAL AND METHODS: In this
      retrospective study we report the incidence, clinical forms, histology and
      management of thyroid and thymic synchronous lesions encountered in as eries of
      82 consecutive patients with various types of Hp operated on in the last three
      decades. Demography, clinical records, biochemical data, imaging procedures,
      pathology reports and surgical protocols were revised. RESULTS: Between 1984
      2013, 82 cases of Hp, 20 primary and 62 renal (27 secondary and 35 tertiary), 57
      women and 25 males (sex ratio: 2.3 1) of 15-72 (mean 46.5) years, under went
      surgery in our clinic. Concomitant thyroid exereses were performed in 32 patients
      (2 subtotal thyroidectomies, 12 lobectomies, 8 atypical resections and 10
      diagnosis biopsies), foruni- or bilateral (multi)nodular goiters or different
      ??minutelesions. Pathology showed 11 colloid goiters, 3 follicular adenomas,5
      nodular hyperplasias and 6 thyroiditis cases, 3 papillary microcarcinomas and 4
      specimens with normal thyroid tissue.Excision of the fibrofatty retromanubrial
      tissue in total parathyroidectomies for renal Hp (19 cases) revealed one
      nonmyastenicthymoma, one thymic cyst and thymic remnants in 6 patients.Morbidity
      in these extended operations was not significantly increased, comparing to the
      parathyroid exploration alone. DISCUSSIONS AND CONCLUSIONS: Meticulous pre- and
      intraoperative evaluation in all cases of Hp enables the actual shift from
      bilateral neck exploration to minimally invasive surgery,increasing however the
      potential risk of missing thyroid or thymic coexistent significant lesions. The
      surgeon dedicated to this pathology must be aware of the possibility of
      encountering such synchronous association and make generous efforts to wards
      their complete cure in a single operation.

PMID- 25560497
TI  - Emergent endovascular repair of ruptured abdominal and thoracic aortic aneurysms
      in a single center: midterm outcomes.
AB  - OBJECTIVE: Endovascular therapies may offer distinct advantages in acute aortic
      syndromes. In this paper, we present our experience with emergent endovascular
      repair of both abdominal and thoracic aortic ruptures and report early and
      midterm out comes. METHODS: Data from all patients (n=96) who were treated by
      endovascular procedures between 2004 to 2012 were prospectively collected and
      early-midterm outcomes of the emergency (e) interventions for both abdominal
      (EVAR) and thoracic (TEVAR) aortic ruptures (n=20) were retrospectively analysed.
      RESULTS: The mean age was 65 +- 11 years (range: 27-77 years)and 18 patients
      (90%) were male. Mean follow-up duration was 28 +/- 21.2 months (range=1-57).
      Thirteen patients were treated by eEVAR (65%) and 7 by eTEVAR (35%). One patient
      who had a rupture of the aneurysm at arcus aorta level was treated by hybrid
      procedure (eTEVAR+ debranching).The hospital mortality rate was 20% (n=4) for all
      cases, 23.0% (n=3) for eEVAR and 14.2% (n=1) for eTEVAR. In the follow-up period,
      3 patients (15.0%) had reinterventions. DISCUSSION: Reinterventions and the
      necessity of close follow-up are the disadvantages of endovascular
      procedures.Even if that is the case, we believe that eEVAR eTEVAR in the acute
      setting of ruptured aorta in patients with suitable anatomy is a lifesaving
      option.

PMID- 25560498
TI  - Multivisceral echinococcosis: concept, diagnosis, management.
AB  - INTRODUCTION: Hydatid disease is in a come-back period. In Romania the incidence
      is cited at 5-6 cases per 100,000 inhabitants. MATERIAL AND METHOD: In this study
      we define the concept of multivisceral echinococcosis, which is a more serious
      form of the hydatid disease with implications of diagnosis, treatment,morbidity
      and mortality. Multivisceral echinococcosis must be differentiated from multiple
      echinococcosis. The latter is defined as the localization of multiple hydatid
      cysts in the same organ. In case of multiple echinococcosis, we can describe
      double echinococcosis (two hydatid cysts located in the same organ), triple, etc.
      The etiology of multivisceral echinococcosis is similar to mono-visceral
      echinococcosis.Regarding the pathogenic mechanism, we appreciate that there are
      two distinct mechanisms: primary infection (most of them) and secondary
      infection. DISCUSSION: We propose a classification of multivisceral
      echinococcosis based on the anatomical compartment involved.The diagnosis of this
      condition is easy to establish using classicor more recent investigations (CT,
      MRI). Compared to monovisceral echinococcosis, the symptomatology is louder
      because of the involvement of several organs and its association with different
      other conditions. CONCLUSIONS: We wish this study to bring more information about
      hydatid disease, but especially about multivisceral echinococcosis.

PMID- 25560499
TI  - Single incision laparoscopic cholecystectomy.
AB  - BACKGROUND: As surgeons embrace the concept of increasingly less invasive
      surgery, techniques using only a single small incision have begun to gain
      traction. Multiple case series managed by a single-incision laparoscopic
      cholecystectomy (SILC) have been published. The objective of this study is to
      describe the short-term outcomes of SILC in our institution. METHODS: A
      retrospective review was done for 51 patients who underwent SILC between 2009
      2012. The operative time, surgical technique, conversion rate, and postoperative
      complications were reported. RESULTS: SILC was performed for 51 patients, all
      women, with a mean age of 35.6 years (range=19-62). Their body mass index(BMI)
      ranged from 16.8-35.6 kg m2 with a mean of 20.4. Twelve patients (23.52 %) had
      acute cholecystitis. The mean operating time was 58.6 minutes (range=45-95 min).
      Incidents were encountered in 6 patients (11.76%) and were related to
      intraoperative bleeding. There was a single conversion to the standard
      laparoscopic procedure (1.9%) and in 5 cases an accessory needle grasp was used
      (9.8%). Two patients (3.9%)presented postoperative complications (wound
      infections) and the mean hospital stay was 1.6 days. CONCLUSIONS: SILC is
      feasible and provides a promising alternative to natural orifice transluminal
      endoscopic surgery for scarless laparoscopic cholecystectomy. However, routine
      application of this novel technique requires an evaluation of its safety and cost
      effectiveness in larger studies.

PMID- 25560500
TI  - Surgical strategies in severe acute pancreatitis (SAP): indications,
      complications and surgical approaches.
AB  - BACKGROUND: Severe acute pancreatitis (SAP) is still related to high mortality
      rates. This study evaluated the various surgical strategies for treatment of
      suspected infected necroziting pancreatitis (INP). METHODS: This retrospective
      study included 212 patients with SAP and INP, who had surgical treatment during
      the period between January 2000 - December 2012 at the Ist Surgical Clinic.
      Surgical approaches included laparostomy with continous postoperative
      retropancreatic lavage, open abdomen strategy, laparotomy with primary abdominal
      closure accompanied or not by laparostomy (marsupialization), retroperiostomy
      with retroperitoneal lavage. RESULTS: The overall mortality rate was 34.0
      percent, with 24 percent in laparotomy with continous retropancreatic lavage,11
      percent for retroperitoneostomy and retroperitoneal continous lavage, 71 percent
      for the open abdomen strategy,and 43 percent for laparotomy with closed abdomen(p
      0.001). Acute operations, alcoholic origin, Apache II scores of ?Y10 organ
      dysfunction on admission were independent factors that predisposed patients to
      complications.Colonic necrosis with high mortality rates (53 percent), however
      seemed to be of prognostic relevance. CONCLUSIONS: The conservative approach in
      severe acutepancreatitis is a promising therapeutic concept. Delaying surgery up
      to the third week after onset of disease significantly improves the patients??
      survival. Complications are common in severe necrotizing pancreatitis leading to
      organ failure and need for acute operations. Colonic necros is is an independent
      prognostic factor for survival.

PMID- 25560501
TI  - The role of pelvic bone anatomy in the pathogenesis of inguinal hernia.
AB  - BACKGROUND: a small number of reports have suggested that inpatients with
      inguinal hernia, certain pelvic anatomical traits prevail, which are
      characterized by the low position of the groin, resulting in a marked verticality
      of the inguinal fold.Based on this notion we investigated a possible correlation
      of this anatomical characteristic with hernia development, by applying a simple
      clinical research protocol. METHODS: two groups were formed. A study group
      including 25 adult patients with a history of inguinal hernia or aclinically
      proven inguinal hernia and a control group of 10 individuals of the same age and
      sex distribution with the study group, but with no history of inguinal hernia. On
      anteroposteriorpelvic plain x-rays, we measured Radoievitch'??s angle which is
      formed by the interspinal line and the line passing from the anterior superior
      iliac spine and the pubic tubercle.Mean values of Radoievitch'??s angle were then
      compared between the two groups. RESULTS: patients with inguinal hernia had
      greater values concerning Radoievitcha?'s angle in a statistically significant
      manner when compared to controls (p=0.004). CONCLUSIONS: individual variability
      in the configuration of the adult bony pelvis is an important factor in the
      development of inguinal hernia. Pelvimetry could affect the choice of hernia
      repair and radiological pelvimetry could be included in the preoperative planning
      of hernia repair.

PMID- 25560502
TI  - Appendiceal mucocele: clinical and imaging features of 14 cases.
AB  - PURPOSE: Appendiceal mucocele as a cystic dilatation filled with mucinous
      material is a very rare disease of the appendix vermiformis. Its preoperative
      diagnosis is still acking behind common use of imaging techniques. METHODS:
      Retrospective analysis of the patients with a pathological diagnosis of
      appendiceal mucocele with regard to clinical and imaging features. RESULTS: The
      study group included 14 patients with a mean age of 51 years (range from 17 to 82
      years). Predominant symptoms were pain and feeling of fullness in the right iliac
      fossa in 9(64%) and 5 (36%) patients, respectively. For imaging purposes, use of
      computed tomography resulted in preoperative diagnosis of appendiceal mucocele in
      half of the patients(50%). 93% of the cases underwent appendectomy, and righth
      emicolectomy was performed in one patient (7%). Mucocele and cystadenoma were
      detected in 11 (79%) and 3 (21%)patients, respectively. Presence of acute
      appendicitis and coloncarcinoma were confirmed afterwards histologically in 4
      (29%)and one (7%) patients, respectively. CONCLUSIONS: Despite the common use of
      imaging studies,preoperative diagnosis of appendiceal mucocele is still not
      possible in most of the cases. During surgical treatment,which is tailored
      according to imaging and intraoperative findings, precautionary measures to avoid
      intraperitoneal rupture and dissemination should be taken.

PMID- 25560503
TI  - Surgical treatment in stenosing rectal cancer.
AB  - INTRODUCTION: Rectal cancer represents an important health issue, which involves
      multidisciplinary treatment, posing a major surgical challenge, both in terms of
      diagnosis and treatment. MATERIAL AND METHOD: Between 2009-2013, we analysed 83
      patients with stenosing rectal cancer operated on at the Clinic of General
      Surgery II of Colentina Clinical Hospital and at the Clinic of General Surgery I
      of "Prof. Dr. Al. Trestioreanu"?? Oncology Institute, in Bucharest. Gender
      distribution was: 51 males and 32 females. Average age was 65 years old. The most
      frequently encountered symptoms were colicky abdominal pain and rectorrhagia. 25
      patients presented intestinal occlusion phenomena at admission, the other 58
      cases being in subocclusive stage. RESULTS: In occlusive stages: 17 patients
      presented with resectable tumour, while 8 patients had locally advanced
      neoplastic forms (??frozen pelvis??), left iliac colostomy with tumour biopsy
      being the chosen approach. In subocclusive stages: 5 cases had unresectable
      tumours for which left iliac anus with tumour biopsy was performed; 53 cases
      presented with resectable tumour, for which the Hartmann procedure (12 patients)
      and left iliac colostomy with tumour biopsy (41 patients) were performed.
      Depending on the histopathological result, patients were submitted to radio- and
      chemotherapy.Tumour resection was possible in 70 cases (84.33%), only 34 of these
      (40.96%) being with radical intent. CONCLUSIONS: Treatment for stenosing rectal
      cancer is multimodal,represented by surgical approach, radio- and chemotherapy.
      The rationality behind surgery as a first therapeutic gesture in the given study
      group was represented by the need to treat occlusive type complications, patients
      benefitting subsequently from radio- and chemotherapy. The opportunity of a
      second surgical intervention, with the objective to remove the tumour, was
      established based on the therapeutic response to radio- and chemotherapy.

PMID- 25560504
TI  - Evaluation of CR-POSSUM, original ACPGBI and new ACPGBI scoring systems for
      colorectal cancer surgery.
AB  - PURPOSE: To compare the Colorectal Physiological and Operative Score for
      enUmeration of Mortality and Morbidity (Cr-POSSUM) with the original Association
      of Coloproctology of Great Britain and Ireland (ACPGBI) and new ACPGBI scoring
      systems for their ability to predict mortality after colorectal cancer surgery.
      METHODS: We retrospectively calculated the Cr-POSSUM,original ACPBGI and new
      ACPGBI scores of 105 patients who underwent colorectal cancer surgery. Data were
      obtained from patients'?? medical records and operative notes.Mortality was
      defined as death within 30 days of surgery.Scores were validated by assessing
      their calibration and discrimination. Calibration was assessed using the Hosmer
      Leme show test and corresponding calibration curves. The discriminative
      capability of the models was evaluated using receiver operating characteristic
      (ROC) curve analysis. RESULTS: The observed mortality rate was 4.8 %. The over
      all estimated risks of death of the Cr-POSSUM, original ACPGBI, and new ACPGBI
      scores were 9.92%, 7.35% and 4.20%, respectively. The results of areas under the
      curve(AUC) for Cr-POSSUM, original ACPGBI and new ACPGBI scores were 0.792, 0.844
      and 0.801 respectively. CONCLUSIONS: The Cr-POSSUM, original ACPGBI and new
      ACPGBI scoring syStems are accurate in determining mortality rates and for
      predicting the risks of death in individual patients. The new and original ACPGBI
      scoring systems performed slightly better than the Cr-POSSUM scoring system.

PMID- 25560505
TI  - Involvement of reactive oxygen species in the mechanisms associated with cervical
      cancer specific treatment.
AB  - Cervical cancer represents a genuine health issue in Romania.The courses of
      treatment applied are complex, and the accompanying biochemical mechanisms are
      yet to be fully understood. Thus, radiotherapy, which induces reactive oxygen
      species, can lead to failure of treatment in hypoxic tissues,tissues which are
      difficult to identify due to the small quantity in which these cytotoxic species
      are produced. As a result, the aim of this paper is to identify the production
      and role of reactive oxygen species, as well as the manner of activation of
      endogenous antioxidant defense mechanisms in cervical cancer patients admitted to
      the Oncologic Institute of Bucharest. To this purpose the biochemical parameters
      of oxidative stress were identified in 30 patients with cervical tumour
      localization, prior to surgery. The results obtained have showed that a
      production of reactive oxygen species is identifiable in these patients, having
      lipids as a primary target and leading to their peroxidation. The extension of
      protein oxidative degradation takes place at a much lower value, as well as the
      activation of endogenous antioxidant defence systems, comparing to our
      expectations. To conclude,we consider that when the production of active oxygen
      metabolites takes place in small concentrations, associated with hypoxia, the
      signals transmitted are towards modifying the phenotype under anaerobic
      conditions into one activating neo vascularization, angiogenesis initiation, new
      cell growth and proliferation. The moment that this phase is overcome anew
      oxidative stress is installed, one potentially destructive for biomolecules
      essential to life, but also useful for further treatment, such as radiotherapy.

PMID- 25560506
TI  - Minimally invasive transforaminal lumbar interbody fusion: comparison of two
      techniques.
AB  - BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MI TLIF)
      is very popular in the United States.Two techniques are commonly used, based on
      either tubular or pedicle-screw-based retraction. MATERIALS AND METHODS: Sixty
      patients underwent MI TLIF between 2009 and 2012, using the tubular technique (43
      patients) or screw-based-retractor technique (17 patients).Perioperative
      parameters and 1-year outcomes were reviewed. RESULTS: For the tubular technique,
      the average operative time,blood loss, and hospital stay were 189 min, 170 ml,
      and 3.37 days, respectively. The visual analog scale (VAS) score improved from
      9.7 preoperatively to 2.6 at 1-year postoperatively. There were two incidental
      durotomies, none resulting in a CSF leak.There was one re-intervention for
      removal of a misplaced pedicle screw. For the screw-based-retractor technique,
      the average operative time, blood loss, and hospital stay were 223 min, 257 ml,
      and 3.29 days, respectively. VAS improved from 9.4 to 1.9. One patient who had an
      incidental durotomy developed a postoperative compressive hematoma with resultant
      cauda equina syndrome requiring re-intervention.There were no re-interventions
      for revision of instrumentation.Seven patients were lost at the 1-year visit. The
      fusion rate at 1-year was 100%. CONCLUSION: Both techniques can be used with good
      results,but each technique offers distinct advantages and challenges that can be
      tailored to individual patients.

PMID- 25560507
TI  - Therapeutic management of massive subcutaneous emphysema, bilateral pneumothorax
      and pneumomediastinum after anterior cordectomy for in situ vocal cord carcinoma 
      case report.
AB  - We present the case of a 70 year-old smoker patient, who was admitted in hospital
      for removal of a tumour located on the left vocal cord. After direct suspension
      laryngoscopy (with tumorbiopsy sampling), preliminary histopathological exam
      revealed an in situ carcinoma. At 2 weeks after histopathological confirmation,
      the left vocal cord was removed by anterior approach, under general anesthesia.
      In the first 24 hours after surgery, the patient presented an ischaemic stroke,
      with a deep coma and left hemiplegia, which necessitated mechanical ventilation
      and specific neurological treatment. Under mechanical ventilation, the patient
      developed massive subcutaneous emphysema, bilateral pneumothorax and
      pneumomediastinum,which required tracheostomy and bilateralpleural drainage, in
      order to limit suddenly installed respiratory insufficiency. After an 18-day
      interval of intensive care therapy,the patient was released at home, considered
      to be surgically cured and had a moderate remaining left brachial
      monoplegia,which was almost totally cured in the next six months.

PMID- 25560509
TI  - Congenital agenesis of the inferior vena cava - cause of deep vein thrombosis.
AB  - Agenesis of the inferior vena cava is an extremely rare abnormality, most often
      discovered by accident. This paper reports the case of a 41-year-old male
      patient, admitted to the IIIrd Emergency General Surgery Clinic of the Emergency
      University Hospital with the diagnosis of bilateral pelvic limb post-thrombotic
      syndrome. According to his personal history he had the first vascular surgical
      intervention at the age of 6. The surgical indication was determined by large
      hydrostatic varicoseveins of the lower limbs and the performed surgery was
      cosectomy with bilateral stripping of the great saphenousvein. Until admission to
      our clinic, the patient had repeated surgery for recurrent varicose veins of the
      lower limbs. The patient was diagnosed in our service with congenital agenesis of
      inferior vena cava, the evolution was good and the patient was discharged after
      17 days. This paper presents the clinical,imagistic and therapeutic
      particularities of such a case. Imagistic detection of early vascular
      abnormality, identifying procoagulant factors and the close care of the local
      lesion areessential for patient evolution.

PMID- 25560508
TI  - Hypertensive late hemothorax following left pneumonectomy.
AB  - INTRODUCTION: Lung cancer is an extremely serious disease, in most cases the
      onset of symptoms comes in late stages of the disease. Local and distant tumor
      development limits the surgical indication, many times the surgical act being a
      heroic one. Out of all pulmonary resections pneumonectomies are real challenges
      as possible postoperatory complications can be life-threatening. MATERIALS AND
      METHOD: We present the case of a 66 year-old female patient at the time of
      surgery, diagnosed with locally advanced adenocarcinoma of the left lung (lower
      lobe tumor invading the upper lobe), who sustained left pneumonectomy with
      mediastinal lymphadenectomy in March 2012. Immediate postoperative evolution was
      favorable" gradual reduction of the residual cavity, with left shift of the
      mediastinum?" basically a normal post-pneumonectomy course. RESULTS: Upon
      imagistic control at one year postoperatively the following was observed: the
      residual cavity had increased in size under the pressure of a fluid which instead
      of diminishing in quantity was present in a significantly higher volume than on
      previous postoperative examinations. The general consensus was that we are
      dealing with pleural metastases which were producing excess pleural fluid. The
      evolution of the patient and subsequent surgical interventions have demonstrated
      that the first impression is not always the truth. CONCLUSION: There are cases,
      like the one presented, which seem without therapeutic solution. Upon careful
      analysis, dubled by perseverance, these cases benefit from spectacular results
      which break down grim hypotheses previously formed. Associated pathology can
      create in these cases an unbalance in the organism, which will negatively
      influence local postoperative evolution.

PMID- 25560510
TI  - Allograft inflow - concern in liver transplantation after intraoperative
      radiotherapy for cholangiocarcinoma.
AB  - Patients who underwent local radiotherapy during surgical resection for
      cholangiocarcinoma are at increased risk of developing extensive thrombosis of
      splanchnic vessels and secondary biliary cirrhosis on the remnant liver; hence
      they become liver transplantation candidates. In these recipients, adequate graft
      inflow cannot be provided by conventional liver transplantation procedures.
      Cavoportal hemitransposition and renoportal anastomosis alongside complex
      arterial reconstructions are innovative techniques to restore allograft inflow in
      such cases. We report two cases of hilar cholangiocarcinoma formerly treated by
      left hepatectomy-Whipple en Bloc and intraoperative radiotherapy that developed
      late secondary biliary cirrhosis requiring liver transplantation. During
      transplant procedure, concern has been raised by the previous radiation-induced
      peritoneal injury with extended splanchnicthrombosis. Cavoportal
      hemitransposition and renoportal anastomosis were performed respectively, beside
      arterial graft reconstructions. Patients survived 57 and 18 days respectively,
      after transplantation. Cavoportal hemitransposition and renoportal anastomosis
      likewise complex arterial reconstructions are life-saving procedures to secure
      allograft inflow in the setting of radiation-induced extensive splanchnic
      thrombosis. However,this condition adversely affects patient and graft survival
      owing to high rates of early vascular and biliary complications, so these
      patients are not good liver transplantation candidates. ABBREVIATIONS: CCA -
      cholangiocarcinoma, CPHT - cavoportal hemitrans position, Ct - celiac trunk, DSVT
      - diffusesplanchnic vein thrombosis, HA - hepatic artery, IVC - inferior vena
      cava, LRV - left renal vein, LT - liver transplantation, PV- portal vein, PVT -
      portal vein thrombosis, RISC -radiation induced sclerosing cholangitis, RISC-BC -
      radiationinduced sclerosing with biliary cirrhosis, RPA - renoportal anastomosis.

PMID- 25560511
TI  - Collision tumor of the appendix: mucinous cystadenoma and carcinoid. A case
      report.
AB  - INTRODUCTION: Mucinous cystadenoma is the most common of benign neoplasms of the
      appendix and carcinoid is the most common type of primary malignant lesions of
      the appendix.We report a rare case of a 57-year-old female with combined mucinous
      cystadenoma and carcinoid tumor of the appendix.Dual carcinoid and epithelial
      neoplasia is a rare occurrence in the appendix. CASE REPORT: A 57-year-old
      Caucasian woman presented after incidentally palpating a mass on her right iliac
      fossa. Imaging modalities revealed a cystic tumor in the right iliac fossa with a
      diameter of about 8 cm, originating either from the right ovary or the appendix.
      She underwent laparoscopic surgical exploration, which revealed appendiceal
      mucocele and appendicectomy was finally performed as well as excision of a right
      ovarian cyst. Pathological examination showed acollision tumor consisting of
      mucinous cystadenoma and carcinoid tumor of the appendix. Because of the size and
      extension of the carcinoid tumor, which the pathology report revealed, she
      underwent re-exploration and laparoscopic right colectomy. DISCUSSION: Mucinous
      cystadenoma is rare, but it is the commonest of benign appendiceal tumours
      accounting for 0.6% of appendectomy specimens. It can present as
      appendicitis,mucocele or if the tumour ruptures, as pseudomyxomaperitonei. On the
      other hand, carcinoid is the most common type of primary malignant lesion of the
      appendix and 0.3-0.9%of appendectomy specimens, with small predominance in female
      patients. Rare cases of mucinous cystadenomas of the appendix coexisting with
      carcinoid tumors were reported before, but in our case it was a collision tumor
      with no transitional zone between them. Also, the clinical presentation of our
      patient and the differential diagnosis of ovarian lesions from appendiceal tumors
      is worth being mentioned.

PMID- 25560512
TI  - Pseudomixoma peritonei, a rare entity difficult to diagnose and treat - case
      report.
AB  - The authors present the case of a 56 year-old patient diagnosed with pseudomyxoma
      peritonei, 4 years after being subjected to a left adnexectomy for ovarian
      cystadenoma. The intra-parietal insemination of the mucinous cells enabled the
      development,at this level, of a gelatinous mass that raised problems of
      differential diagnosis with irreducible incisional hernia. In what regards the
      preoperative signs of clinical and paraclinical diagnosis we consider them
      obscure and nonspecific. The abdominal computed tomography revealed the presence
      of a massive intraperitoneal collection, but given the rarity of this pathology
      the initial diagnosis was made in the course of the exploratory laparotomy.
      Intraoperatively it became necessary to perform the omentectomy and total
      hysterectomy with contralateral adnexectomy and appendectomy. The
      histopathological examination confirmed the diagnosis. Using cisplatin associated
      with aggressive surgical cytoreduction this case of pseudomixoma had a good long
      term evolution. The diagnosis was a challenge, and the nonspecific slow evolution
      of the disease led to difficult differential diagnostic.

PMID- 25560513
TI  - Retrorectal dermoid cyst manifested as an extrasphincteric perianal fistula -
      case report.
AB  - Retrorectal tumors are very rare but well defined pathological entities in the
      literature. Also, an extrasphincteric fistula is a very rare form of perianal
      fistula which makes our case a very unusual and rare one, especially by the fact
      that it was successfully treated with the first operation and without protective
      stoma formation. The patient was first treated in hospital for a retrorectal
      abscess that had spontaneously ruptured in the postanal space. Because of the
      constant drainage of the suppurative content from the postanal opening in the
      following months, MRI and fistulography were performed, registering cystic
      formation in the retrorectal space with fistulous communication with the rectum
      above and completely separate from the sphincter mechanism. After that the
      patient was admitted for definitive treatment. The operation was performed with
      the patient in a prone jack-knife position. Complete excision of the cyst with
      the fistulous communication was performed and the rectum was sutured in two
      layers with separate slowly absorbable sutures. The wound was laid open and the
      patient was discharged on the 5th post operative day. After about ten months the
      defecation is normal, the wound is sealed and there are no signs of inflammation
      and secretion locally.

PMID- 25560514
TI  - Transvaginal coloanal anastomosis after rectal resection for the treatment of a
      rectovaginal fistula induced by radiation.
AB  - Although decreasing in number, radiation induced rectovaginal fistulas are caused
      by some radiation injuries and chronic ischemic lesions. Most of the experienced
      authors recommend anterior rectal resection with coloanal anastomosis accessed
      through the abdominal-perineum area for high fistula. We present a patient with a
      fistula that developed 23 years after hysterectomy and radiotherapy. In this case
      we performed an abdominal-transvaginal rectal resection with transverse
      coloplastypouch, coloanal anastomosis and protection ileostomy three months after
      a terminal sigmoidostomy. The dissection of the distal rectum by posteriour
      colpotomy and coloanal transvaginalan astomosis is a technical variant that may
      prove advantage ous compared to the procedures featured in the literature as
      solutions by rectal resection for rectovaginal fistula.

PMID- 25560515
TI  - Secondary extracranial meningiomas extending into the paranasal sinuses.
AB  - Meningiomas are well-recognized tumors of the central nervous system.
      Extracranial meningiomas, secondarily extended into the paranasal sinuses, are
      rare tumors, comprising approximately 2% of all meningiomas. Extracranial
      meningiomas of the paranasal sinuses may present a diagnostic and the rapeutic
      challenge. We present a retrospective review comprising three cases and discuss
      the clinical presentation, imaging findings,diagnostic evaluation, and treatment
      options. The localizations included the frontal sinus, the ethmoid sinus, the
      sphenoid sinus and even the maxillary sinus. Complete surgical resection was
      achieved in one patient; meanwhile deliberate subtotal tumor resection was
      performed in the other cases in order to avoid severe neurological damage with
      sufficient tumor control.

PMID- 25560516
TI  - A new dynamic null model for phylogenetic community structure.
AB  - Phylogenies are increasingly applied to identify the mechanisms structuring
      ecological communities but progress has been hindered by a reliance on
      statistical null models that ignore the historical process of community assembly.
      Here, we address this, and develop a dynamic null model of assembly by allopatric
      speciation, colonisation and local extinction. Incorporating these processes
      fundamentally alters the structure of communities expected due to chance, with
      speciation leading to phylogenetic overdispersion compared to a classical
      statistical null model assuming equal probabilities of community membership.
      Applying this method to bird and primate communities in South America we show
      that patterns of phylogenetic overdispersion - often attributed to negative
      biotic interactions - are instead consistent with a species neutral model of
      allopatric speciation, colonisation and local extinction. Our findings provide a
      new null expectation for phylogenetic community patterns and highlight the
      importance of explicitly accounting for the dynamic history of assembly when
      testing the mechanisms governing community structure. 

PMID- 25560517
TI  - Resurfaced fluorescent protein as a sensing platform for label-free detection of
      copper(II) ion and acetylcholinesterase activity.
AB  - Protein engineering by resurfacing is an efficient approach to provide new
      molecular toolkits for biotechnology and bioanalytical chemistry. H39GFP is a new
      variant of green fluorescent protein (GFP) containing 39 histidine residues in
      the primary sequence that was developed by protein resurfacing. Herein, taking
      H39GFP as the signal reporter, a label-free fluorometric sensor for Cu(2+)
      sensing was developed based on the unique multivalent metal ion-binding property
      of H39GFP and fluorescence quenching effect of Cu(2+) by electron transfer. The
      high affinity of H39GFP with Cu(2+) (Kd, 16.2 nM) leads to rapid detection of
      Cu(2+) in 5 min with a low detection limit (50 nM). Using acetylthiocholine
      (ATCh) as the substrate, this H39GFP/Cu(2+) complex-based sensor was further
      applied for the turn-on fluorescence detection of acetylcholinesterase (AChE)
      activity. The assay was based on the reaction between Cu(2+) and thiocholine, the
      hydrolysis product of ATCh by AChE. The proposed sensor is highly sensitive
      (limit of detection (LOD) = 0.015 mU mL(-1)) and is feasible for screening
      inhibitors of AChE. Furthermore, the practicability of this method was
      demonstrated by the detection of pesticide residue (carbaryl) in real food
      samples. Hence, the successful applications of H39GFP in the detection of metal
      ion and enzyme activity present the prospect of resurfaced proteins as versatile
      biosensing platforms. 

PMID- 25560522
TI  - Perspectives on the working hours of Australian junior doctors.
AB  - The working hours of junior doctors have been a focus of discussion in Australia
      since the mid-1990s. Several national organizations, including the Australian
      Medical Association (AMA), have been prominent in advancing this agenda and have
      collected data (most of which is self-reported) on the working hours of junior
      doctors over the last 15 years. Overall, the available data indicate that working
      hours have fallen in a step-wise fashion, and AMA data suggest that the
      proportion of doctors at high risk of fatigue may be declining. It is likely that
      these changes reflect significant growth in the number of medical graduates, more
      detailed specifications regarding working hours in industrial agreements, and a
      greater focus on achieving a healthy work-life balance. It is notable that
      reductions in junior doctors' working hours have occurred despite the absence of
      a national regulatory framework for working hours. Informed by a growing
      international literature on working hours and their relation to patient and
      practitioner safety, accreditation bodies such as the Australian Commission on
      Safety and Quality in Health Care (ACSQHC) and the Australian Medical Council
      (AMC) are adjusting their standards to encourage improved work and training
      practices. 

PMID- 25560525
TI  - Editorial.

PMID- 25560523
TI  - SWATH enables precise label-free quantification on proteome scale.
AB  - MS-based proteomics has emerged as a powerful tool in biological studies. The
      shotgun proteomics strategy, in which proteolytic peptides are analyzed in data
      dependent mode, enables a detection of the most comprehensive proteome (>10 000
      proteins from whole-cell lysate). The quantitative proteomics uses stable
      isotopes or label-free method to measure relative protein abundance. The isotope
      labeling strategies are more precise and accurate compared to label-free methods,
      but labeling procedures are complicated and expensive, and the sample number and
      types are also limited. Sequential window acquisition of all theoretical mass
      spectra (SWATH) is a recently developed technique, in which data-independent
      acquisition is coupled with peptide spectral library match. In principle SWATH
      method is able to do label-free quantification in an MRM-like manner, which has
      higher quantification accuracy and precision. Previous data have demonstrated
      that SWATH can be used to quantify less complex systems, such as spiked-in
      peptide mixture or protein complex. Our study first time assessed the
      quantification performance of SWATH method on proteome scale using a complex
      mouse-cell lysate sample. In total 3600 proteins got identified and quantified
      without sample prefractionation. The SWATH method shows outstanding
      quantification precision, whereas the quantification accuracy becomes less
      perfect when protein abundances differ greatly. However, this inaccuracy does not
      prevent discovering biological correlates, because the measured signal
      intensities had linear relationship to the sample loading amounts; thus the SWATH
      method can predict precisely the significance of a protein. Our results prove
      that SWATH can provide precise label-free quantification on proteome scale. 

PMID- 25560526
TI  - Pathology International TOP 100 citation articles.

PMID- 25560527
TI  - Sarcomatoid pleural mesothelioma with osteosarcomatous, chondrosarcomatous and
      rhabdomyoblastic elements: an extremely rare autopsy case.

PMID- 25560528
TI  - Reporting patterns of adverse drug reactions over recent years in China: analysis
      from publications.
AB  - PURPOSE: The goal of this study was to clarify the reporting patterns of self
      reported adverse drug reactions (ADRs) in China. METHODS: A variety of sources
      were searched, including the official website of China FDA, the national center
      for ADR monitoring center, publications from PubMed, and so on. We retrieved the
      relevant information and made descriptive and comparative analysis from the year
      2009 to 2013. RESULTS: The ADR reporting numbers were 638,996, 692,904, 852,799,
      1,200,000 and 1,317,000 from 2009 to 2013, respectively. Healthcare professionals
      contributed significantly, and their proportion always exceeded 80% before 2012.
      The average report per million inhabitants has increased from 479 to 983 from
      2009 to 2013. However, the proportion of new or serious report was always below
      25%. The reports mainly concern anti-infective agents and traditional Chinese
      medicine (TCM), especially TCM injection. The proportion of ADR reports in
      geriatric patients has increased for 4 consecutive years. CONCLUSIONS: ADR report
      numbers and reporting rates in China are on the rise. However, the proportion of
      new or serious reports as well as the proportion of reports contributed by
      consumers and pharmaceutical companies are still quite low. More attention should
      be paid to the elderly, anti-infective agents and TCM, especially TCM injections.

PMID- 25560529
TI  - Glioma in 2014: unravelling tumour heterogeneity-implications for therapy.
AB  - Heterogeneity within and across tumours is increasingly recognized as a critical
      factor that limits therapeutic progress for many cancers. Key studies reported in
      2014 describe previously unappreciated patterns of geographical and temporal
      heterogeneity for glioblastoma (the most-common primary CNS tumour in adults),
      with important implications for ongoing therapeutic studies evaluating molecular
      targeted therapies.

PMID- 25560530
TI  - Genetics: HotNet2-see the wood for the trees.

PMID- 25560531
TI  - Targeted therapies: new standard for ALK-positive NSCLC.

PMID- 25560532
TI  - Breast cancer in 2014: A call back to reality!
AB  - In 2014, no major breakthroughs were made in understanding the biology of breast
      cancer or its management; few novel practice-changing studies were presented or
      published. Nevertheless, important negative results from studies that challenge
      some of the current concepts, particularly in drug development, underline 2014 as
      a year of 'failed surrogates and precocious expectations'.

PMID- 25560533
TI  - Colorectal cancer in 2014: progress in defining first-line and maintenance
      therapies.
AB  - The results of several clinical trials in metastatic colorectal cancer presented
      in 2014 will influence clinical practice. These findings include definitive data
      from phase III trials comparing bevacizumab and cetuximab-based therapy in the
      first-line, studies elucidating the value of maintenance therapy after induction
      treatment, and data on new agents in this disease.

PMID- 25560534
TI  - Treatment of recurrent malignant gliomas with 13-cis-retinoic acid naphthalene
      triazole.
AB  - Glioblastoma multiforme and anaplastic astrocytoma are challenges to clinical
      biologists at present. The patients with glioblastoma have median survival of
      less than 12 months, despite advances in radiotherapeutical, chemotherapeutical
      and conventional surgical modalities. Retinoic acids are known to effect in vitro
      proliferation, differentiation, and apoptosis in colon, prostate, lung, and
      leukemia cancers. Retinoids are known to have anti-proliferation, anti-migration,
      and anti-invasive activity against human malignant gliomas, suggesting that
      retinoids are suitable anticancer agents to inhibit progression of tumors.
      Recurrent malignant cerebral gliomas have been treated with ATRA and 13-cis RA.
      However, the side effects associated with the use of high doses of retinoic acid
      demand for some more potent derivative free from such effects. The present
      clinical trials are undertaken to investigate the clinical safety and possible
      efficacy of administering retinoic acid naphthalene triazole (RANT) to patients
      with recurrent malignant gliomas. The toxicities observed in the patients during
      RANT treatment were mild. These preliminary results suggest that RANT is more
      potent compared to RA against recurrent malignant gliomas.

PMID- 25560535
TI  - Prestroke glycemic status is associated with the functional outcome in
      spontaneous intracerebral hemorrhage.
AB  - Admission hyperglycemia is thought to be related to poor neurological function
      and high mortality in patients with spontaneous intracerebral hemorrhage (sICH).
      However, it is not known whether prestroke glycemic status affects functional
      outcome of sICH. The study was aimed to disclose the association between
      prestroke glycemic status and outcome in patients with sICH. The study included
      288 patients with sICH. Prestroke glycemic status was represented by hemoglobin
      A1c (HbA1c) values measured the next day after admission. Correlations between
      HbA1c and age, hematoma volume, NIHSS, and mRS were analyzed using Spearman's
      correlation analysis. Patients were categorized into two groups according to
      hematoma volume (<=25 mL or >25 mL), mRS values (<=2 or >2), or hematoma location
      (lobar hematoma or deep hematoma). Logistic regression analyses were used to
      determine the relative independent risk factors for hematoma volume, hematoma
      location, and mRS values. In patients with sICH, HbA1c was significantly
      correlated with hematoma volume, NIHSS, and mRS. High HbA1c levels were
      independently associated with large hematoma volume, deep ICH, and poor outcome.
      When patients were stratified by history of diabetes, the predictive effect of
      HbA1c on outcomes was only observed in patients with diabetes. Admission glucose
      was also related to hematoma volume, but failed to predict outcome. Although both
      admission glucose and HbA1c independently predicted hematoma volume in patients
      with sICH, HbA1c alone could serve as a better predictor of poor outcome in
      diabetic patients after sICH.

PMID- 25560536
TI  - TIGAR2: sensitive and accurate estimation of transcript isoform expression with
      longer RNA-Seq reads.
AB  - BACKGROUND: High-throughput RNA sequencing (RNA-Seq) enables quantification and
      identification of transcripts at single-base resolution. Recently, longer
      sequence reads become available thanks to the development of new types of
      sequencing technologies as well as improvements in chemical reagents for the Next
      Generation Sequencers. Although several computational methods have been proposed
      for quantifying gene expression levels from RNA-Seq data, they are not
      sufficiently optimized for longer reads (e.g. >250 bp). RESULTS: We propose
      TIGAR2, a statistical method for quantifying transcript isoforms from fixed and
      variable length RNA-Seq data. Our method models substitution, deletion, and
      insertion errors of sequencers based on gapped-alignments of reads to the
      reference cDNA sequences so that sensitive read-aligners such as Bowtie2 and BWA
      MEM are effectively incorporated in our pipeline. Also, a heuristic algorithm is
      implemented in variational Bayesian inference for faster computation. We apply
      TIGAR2 to both simulation data and real data of human samples and evaluate
      performance of transcript quantification with TIGAR2 in comparison to existing
      methods. CONCLUSIONS: TIGAR2 is a sensitive and accurate tool for quantifying
      transcript isoform abundances from RNA-Seq data. Our method performs better than
      existing methods for the fixed-length reads (100 bp, 250 bp, 500 bp, and 1000 bp
      of both single-end and paired-end) and variable-length reads, especially for
      reads longer than 250 bp.

PMID- 25560537
TI  - Genetic testing and FDA regulation: overregulation threatens the emergence of
      genomic medicine.

PMID- 25560538
TI  - Effect of personalized nutritional counseling in maintenance hemodialysis
      patients.
AB  - Monitoring nutritional parameters is an integral part of hemodialysis (HD)
      patient treatment program. The purpose of this study was to evaluate the impact
      of the personalized nutritional counseling (PNC) on calcium-phosphorus
      metabolism, potassium, albumin, protein intake, interdialytic weight gain (IDWG),
      body composition parameters and fluid overload in HD patients. This was a
      multicenter longitudinal intervention study with 6 months of follow-up and 731
      patients on maintenance HD from 34 dialysis units in Portugal were enrolled.
      Biochemical and body composition parameters were measured at baseline, 1, 3 and 6
      months after the PNC. Patient's mean age was 64.9 (95% confidence interval [CI]:
      63.8-66.0) years and mean HD time was 59.8 (95% CI: 55.3-64.3) months. Regarding
      data comparison collected before PNC vs. 6 months after, we obtained,
      respectively, the following results: patients with normalized protein catabolic
      rate (nPCR) >= 1 g/kg/day = 66.5% vs. 73.5% (P = 0.002); potassium > 5.5 mEq/L =
      52% vs. 35.8% (P < 0.001); phosphorus between 3.5 and 5.5 mg/dL = 43.2% vs. 52.5%
      (P < 0.001); calcium/phosphorus (Ca/P) ratio <= 50 mg/dL = 73.2 % vs. 81.4% (P <
      0.001); albumin >= 4.0 g/dL = 54.8% vs. 55% (P = 0.808); presence of relative
      overhydration = 22.4% vs. 25% (P = 0.283); IDWG > 4.5% = 22.3% vs. 18.2% (P =
      0.068). PNC resulted in a significant decrease in the prevalence of hyperkalemia,
      hypophosphatemia and also showed amelioration in Ca/P ratio, nPCR and an increase
      in P of hyphosphatemic patients. Our study suggests that dietetic intervention
      contributes to the improvement of important nutritional parameters in patients
      receiving hemodialysis treatment. 

PMID- 25560540
TI  - Acute injuries in track and field athletes: a 3-year observational study at the
      Penn Relays Carnival with epidemiology and medical coverage implications.
AB  - BACKGROUND: Few studies have examined acute injuries in track and field in both
      elite and subelite athletes. PURPOSE: To observe the absolute number and relative
      rates of injury in track and field athletes across a wide range of competition
      levels and ages during 3 years of the Penn Relays Carnival to assist with future
      medical coverage planning and injury prevention strategies. STUDY DESIGN:
      Descriptive epidemiology study. METHODS: Over a 3-year period, all injuries
      treated by the medical staff were recorded on a standardized injury report form.
      Absolute number of injuries and relative injury rates (number of injuries per
      1000 competing athletes) were determined and odds ratios (ORs) of injury rates
      were calculated between sexes, competition levels, and events. Injuries were also
      broken down into major or minor medical or orthopaedic injuries. RESULTS:
      Throughout the study period, 48,473 competing athletes participated in the Penn
      Relays Carnival, and 436 injuries were sustained. For medical coverage purposes,
      the relative rate of injury subtypes was greatest for minor orthopaedic injuries
      (5.71 injuries per 1000 participants), followed by minor medical injuries (3.42
      injuries per 1000 participants), major medical injuries (0.69 injuries per 1000
      participants), and major orthopaedic injuries (0.18 injuries per 1000
      participants). College/elite athletes displayed the lowest relative injury rate
      (7.99 injuries per 1000 participants), which was significantly less than that of
      high school (9.87 injuries per 1000 participants) and masters athletes (16.33
      injuries per 1000 participants). Male athletes displayed a greater likelihood of
      having a minor orthopaedic injury compared with female athletes (OR, 1.36 [95%
      CI, 1.06-1.75]; chi2 = 5.73; P = .017) but were less likely to sustain a major
      medical injury (OR, 0.33 [95% CI, 0.15-0.75]; chi2 = 7.75; P = .005). Of the 3
      most heavily participated in events, the 4 * 400-m relay displayed the greatest
      relative injury rate (13.6 injuries per 1000 participants) compared with the 4 *
      100-m and 4 * 200-m relays. CONCLUSION: Medical coverage teams for future large
      scale track and field events need to plan for at least 2 major orthopaedic and 7
      major medical injuries per 10,000 participants. Male track and field athletes,
      particularly masters male athletes, are at greater risk of injury compared with
      other sexes and competition levels.

PMID- 25560539
TI  - Agreement between athlete-recalled and clinically documented concussion histories
      in former collegiate athletes.
AB  - BACKGROUND: Athlete-recalled and clinically documented concussion histories have
      been used in research on former athletes, but both have limitations. Comparisons
      of these 2 types of concussion histories are needed to improve the accuracy of
      estimates of concussion history for future research and clinical care. PURPOSE:
      To estimate the agreement between athlete-recalled and clinically documented
      concussion histories during college and to explore reasons for differences.
      STUDY: Cohort study (diagnosis); Level of evidence, 3. METHODS: Athlete-recalled
      concussion histories were provided by a convenience sample of 130 former
      collegiate athletes using an online questionnaire, and they were individually
      linked to previously collected clinical data that tracked medically diagnosed
      concussions at the host institution from 1996 to 2012. The intraclass correlation
      coefficient (ICC2,1) was used to assess agreement between athlete-recalled and
      clinically documented concussion histories. Descriptive analyses were performed
      to assess reasons for disagreement. RESULTS: Agreement between athlete-recalled
      and clinically documented concussion histories was low (ICC2,1 = 0.21; 95%
      confidence interval, 0.05-0.37), but it was higher for women (ICC2,1 = 0.65; 95%
      confidence interval, 0.44-0.79) and for athletes playing more recently (2005
      2012; ICC2,1 = 0.39; 95% confidence interval, 0.01-0.67). Of the 53 athletes who
      self-reported college sports-related concussions, 40% believed that they
      sustained impacts that should have been diagnosed as concussions but were
      undetected, and 21% admitted nondisclosure of suspected concussions. Common
      reasons for nondisclosure included the following: did not think injury was
      serious enough (91%), did not know it was a concussion (73%), and did not want to
      leave the game/practice (73%). CONCLUSION: Given the low agreement between
      athlete-recalled and clinically documented concussion histories, methodologic
      research is needed to improve the quality of tools used to assess concussion
      histories in former athletes.

PMID- 25560541
TI  - Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by
      localized, systemic, and liposomal administration.
AB  - Cytochalasin B is a potentially novel microfilament-directed chemotherapeutic
      agent that prevents actin polymerization, thereby inhibiting cytokinesis.
      Although cytochalasin B has been extensively studied in vitro, only limited data
      are available to assess its in vivo potential. Cytochalasin B was administered to
      Balb/c mice challenged i.d. with M109 murine lung carcinoma to determine whether
      the agent could affect an established i.d. tumor when the compound is
      administered s.c. in the region of the i.d. tumor, but not in direct contact with
      it. Cytochalasin B was also administered either i.p. or s.c. at a distant site or
      i.v. to determine whether it could affect the long-term development of an
      established i.d. tumor. Cytochalasin B was then liposome encapsulated to
      determine whether the maximum tolerated dose (MTD) of the compound could be
      increased, while reducing immunosuppression that we have previously
      characterized. Liposomal cytochalasin B was also administered to mice challenged
      i.d. with M109 lung carcinoma to assess its chemotherapeutic efficacy. The
      results can be summarized as follows: 1) cytochalasin B substantially delayed the
      growth of i.d. M109 tumor nodules, inhibited metastatic progression in
      surrounding tissues, and produced long-term cures in treated mice; 2) liposomal
      cytochalasin B increased the i.p. MTD by more than 3-fold, produced a different
      distribution in tissue concentrations, and displayed antitumor effects against
      M109 lung carcinoma similar to non-encapsulated cytochalasin B. These data show
      that cytochalasin B exploits unique chemotherapeutic mechanisms and is an
      effective antineoplastic agent in vivo in pre-clinical models, either in bolus
      form or after liposome encapsulation. 

PMID- 25560542
TI  - High-pressure orthorhombic ferromagnesite as a potential deep-mantle carbon
      carrier.
AB  - Knowledge of the physical and chemical properties of candidate deep-carbon
      carriers such as ferromagnesite [(Mg,Fe)CO3] at high pressure and temperature of
      the deep mantle is necessary for our understanding of deep-carbon storage as well
      as the global carbon cycle of the planet. Previous studies have reported very
      different scenarios for the (Mg,Fe)CO3 system at deep-mantle conditions including
      the chemical dissociation to (Mg,Fe)O+CO2, the occurrence of the tetrahedrally
      coordinated carbonates based on CO4 structural units, and various high-pressure
      phase transitions. Here we have studied the phase stability and compressional
      behavior of (Mg,Fe)CO3 carbonates up to relevant lower-mantle conditions of
      approximately 120 GPa and 2400 K. Our experimental results show that the
      rhombohedral siderite (Phase I) transforms to an orthorhombic phase (Phase II
      with Pmm2 space group) at approximately 50 GPa and 1400 K. The structural
      transition is likely driven by the spin transition of iron accompanied by a
      volume collapse in the Fe-rich (Mg,Fe)CO3 phases; the spin transition stabilizes
      the high-pressure phase II at much lower pressure conditions than its Mg-rich
      counterpart. It is conceivable that the low-spin ferromagnesite phase II becomes
      a major deep-carbon carrier at the deeper parts of the lower mantle below 1900 km
      in depth.

PMID- 25560543
TI  - DNA photochemistry: geometrically unconstrained pyrimidine (6-4) pyrimidone
      photoproducts do photoisomerize.
AB  - Structural features are of major importance for the formation of mutagenic
      photoproducts in DNA. It was recently reported that lack of constraints between
      two adjacent nucleosidic units prevents the conversion of pyrimidine (6-4)
      pyrimidone photoproducts into their Dewar valence isomers. We here report that
      this is not the case for the thymidine photoproducts which, although
      unconstrained, are quantitatively converted into photolysis products identified
      as Dewar valence isomers by mass spectrometry and NMR and infrared
      spectroscopies. 

PMID- 25560545
TI  - Ligation under vision in the management of symptomatic hemorrhoids: A preliminary
      experience.
AB  - AIM: To evaluate the surgical outcomes of 47 patients who underwent hemorrhoidal
      arterial ligation under vision (LUV) for symptomatic Grade II and Grade III
      hemorrhoids. METHODS: A total of 47 patients who underwent LUV between May 2005
      and February 2009 were analyzed retrospectively. The patients were evaluated with
      regard to demographic data, grade of the disease, symptoms, medical and/or
      surgical treatment previously received, operation time, pain scores, analgesic
      requirement, length of hospital stay, and complications related to the procedure.
      RESULTS: The study population (n = 47) included 31 (65.9%) men and 16 (34.1%)
      women with a median age of 37.4 +/- 11.7 (range, 19-63) years. Of these 47
      patients, 18 (38.3%) patients had Grade II hemorrhoidal disease (HD) and 29
      (61.7%) patients had Grade III HD. On average, six ligatures (range, 3-8) were
      used. The mean operation time was 27 +/- 4.8 (range, 15-35) minutes. No major
      complication that required surgical intervention occurred in the early
      postoperative period for any of the patients except for two patients with rectal
      submucosal hematoma. The mean hospital stay was 1.2 +/- 0.65 (range, 1-4) days.
      The median follow-up period was 21.5 +/- 7.7 (range, 12-44) months. At the last
      follow-up, 38 (80.8%) patients remained asymptomatic; two (4.2%) patients with
      Grade II HD and four (8.5%) patients with Grade III HD were still suffering from
      bleeding but with a reduction in the frequency; prolapsed hemorrhoids were
      detected only in three (6.3%) patients. CONCLUSION: LUV is a safe and easily
      applied alternative technique with low postoperative complications for the
      surgical treatment of symptomatic Grade II and III HD.

PMID- 25560544
TI  - Successful extracorporeal resuscitation after perioperative anaphylactic shock
      during living donor liver transplantation.
AB  - A 46-year-old man was admitted for emergent donor hepatectomy. His circulatory
      condition became unstable 75 minutes after induction and then deteriorated to
      ventricular fibrillation due to latex-induced anaphylaxis. Following 35 minutes
      of futile conventional resuscitation without spontaneous cardiac rhythm,
      extracorporeal resuscitation was initiated and electric cardiac activity returned
      10 minutes later. He was discharged home without any sequelae. Extracorporeal
      cardiopulmonary resuscitation would offer an alternative choice compared with
      conventional cardiopulmonary resuscitation.

PMID- 25560546
TI  - Equilibrium constant for the reaction ClO + ClO <-> ClOOCl between 250 and 206 K.
AB  - The chlorine peroxide molecule, ClOOCl, is an important participant in the
      chlorine-catalyzed destruction of ozone in the stratosphere. Very few laboratory
      measurements have been made for the partitioning between monomer ClO and dimer
      ClOOCl at temperatures lower than 250 K. This paper reports absorption spectra
      for both ClO and ClOOCl when they are in equilibrium at 1 atm and temperatures
      down to 206 K. The very low ClO concentrations involved requires measuring and
      calibrating a differential cross section, DeltasigmaClO, for the 10-0 band of
      ClO. A third law fit of the new results gives Keq = [(2.01 +/- 0.17) 10-27 cm3
      molecule-1] e(8554?21)K/T, where the error limits reflect the uncertainty in the
      entropy change. The resulting equilibrium constants are slightly lower than
      currently recommended. The slope of the van't Hoff plot yields a value for the
      enthalpy of formation of ClOOCl at 298 K, DeltaHfo, of 129.8 +/- 0.6 kJ mol-1.
      Uncertainties in the absolute ultraviolet cross sections of ClOOCl and ClO appear
      to be the limiting factors in these measurements. The new Keq parameters are
      consistent with the measurements of Santee et al.42 in the stratosphere.

PMID- 25560548
TI  - Erratum to: The effect of climate variability on urinary stone attacks: increased
      incidence associated with temperature over 18  degrees C: a population-based
      study.

PMID- 25560547
TI  - Development and assessment of an e-learning course on breast imaging for
      radiographers: a stratified randomized controlled trial.
AB  - BACKGROUND: Mammography is considered the best imaging technique for breast
      cancer screening, and the radiographer plays an important role in its
      performance. Therefore, continuing education is critical to improving the
      performance of these professionals and thus providing better health care
      services. OBJECTIVE: Our goal was to develop an e-learning course on breast
      imaging for radiographers, assessing its efficacy, effectiveness, and user
      satisfaction. METHODS: A stratified randomized controlled trial was performed
      with radiographers and radiology students who already had mammography training,
      using pre- and post-knowledge tests, and satisfaction questionnaires. The primary
      outcome was the improvement in test results (percentage of correct answers),
      using intention-to-treat and per-protocol analysis. RESULTS: A total of 54
      participants were assigned to the intervention (20 students plus 34
      radiographers) with 53 controls (19+34). The intervention was completed by 40
      participants (11+29), with 4 (2+2) discontinued interventions, and 10 (7+3) lost
      to follow-up. Differences in the primary outcome were found between intervention
      and control: 21 versus 4 percentage points (pp), P<.001. Stratified analysis
      showed effect in radiographers (23 pp vs 4 pp; P=.004) but was unclear in
      students (18 pp vs 5 pp; P=.098). Nonetheless, differences in students' posttest
      results were found (88% vs 63%; P=.003), which were absent in pretest (63% vs
      63%; P=.106). The per-protocol analysis showed a higher effect (26 pp vs 2 pp;
      P<.001), both in students (25 pp vs 3 pp; P=.004) and radiographers (27 pp vs 2
      pp; P<.001). Overall, 85% were satisfied with the course, and 88% considered it
      successful. CONCLUSIONS: This e-learning course is effective, especially for
      radiographers, which highlights the need for continuing education.

PMID- 25560549
TI  - Complex effects of inbreeding on biparental cooperation.
AB  - There is mounting evidence that inbreeding can have detrimental effects on the
      fitness of outbred individuals that interact with or depend on inbred
      individuals. However, little is currently known about the behavioral mechanisms
      by which interactions with inbred individuals induce fitness costs in outbred
      individuals. Here, we study effects of inbreeding on the behavioral dynamics of
      biparental cooperation in the burying beetle Nicrophorus vespilloides. To this
      end, we used a two-by-two factorial design, in which an inbred or outbred female
      was mated to an inbred or an outbred male and tested for effects on cooperation
      between male and female parents providing care for their joint offspring. We
      found no evidence that inbred parents provided less care than outbred parents.
      Nevertheless, partners of inbred parents increased the amount of care they
      provided, leading to overcompensation. Our study shows that inbreeding can have
      strong and complex effects on the behavioral dynamics of biparental cooperation
      and that these effects are mediated mainly through changes in the partner's
      behavior. We suggest that similar effects of inbreeding on outbred individuals
      may extend to other social contexts, such as cooperative breeding and mating.

PMID- 25560550
TI  - Life-history differences in age-dependent expressions of multiple ornaments and
      behaviors in a lekking bird.
AB  - Age is a major factor explaining variation in life-history traits among
      individuals with typical patterns of increasing trait values early in life,
      maximum trait expression, and senescence. However, age-dependent variation in the
      expressions of sexually selected traits has received less attention, although
      such variation underpins differences in male competitive abilities and female
      preference, which are central to sexual selection. In contrast to previous
      studies focusing on single traits, we used repeated measures of seven sexually
      selected morphological and behavioral traits in male black grouse (Tetrao tetrix)
      to quantify the effects of age and life span on their expressions and quantified
      this variation in relation to male reproductive effort. Trait expression
      increased with age, but long-lived males had a slower increase and delayed maxima
      in trait values compared with short-lived males. There was evidence of terminal
      investment (increasing trait values during the last breeding season) in some
      traits and senescence in all traits. These trait dynamics were largely explained
      by the timing of male peak lekking effort. This study shows that fully
      understanding the variation in sexually selected traits and fitness benefits
      associated with sexual selection requires accounting for the complex interaction
      among individual age, life span, and the timing of individuals' investment in
      reproduction.

PMID- 25560551
TI  - Mating system plasticity promotes persistence and adaptation of colonizing
      populations of hermaphroditic angiosperms.
AB  - Persistence and adaptation in novel environments are limited by small population
      size, strong selection, and maladaptive gene flow. Mating system plasticity is
      common in angiosperms and may provide both demographic and genetic benefits that
      promote niche evolution, including reproductive assurance and isolation from
      maladaptive gene flow. Yet increased self-fertilization may also cause inbreeding
      depression, accumulation of deleterious mutations, and reduced adaptive
      potential. Here we use individual-based simulations to examine the consequences
      of mating system plasticity for persistence and adaptation in a novel environment
      that imposes selection on a quantitative trait. We examine the joint evolution of
      local adaptation, inbreeding depression, and genetic load. We find that a plastic
      shift to a mixed mating system generally promotes niche evolution by decreasing
      the risk of extinction, providing isolation from maladaptive gene flow, and
      temporarily increasing genetic variance in the trait under selection, whereas
      obligate self-fertilization reduces adaptive potential. These effects are most
      pronounced under conditions of mate limitation, strong selection, or maladaptive
      gene flow. Our results highlight the diverse demographic and genetic consequences
      of self-fertilization and support the potential role for plastic shifts in mating
      system to promote niche evolution in flowering plants.

PMID- 25560552
TI  - Effects of environmental disturbance on phenotypic variation: an integrated
      assessment of canalization, developmental stability, modularity, and allometry in
      lizard head shape.
AB  - When populations experience suboptimal conditions, the mechanisms involved in the
      regulation of phenotypic variation can be challenged, resulting in increased
      phenotypic variance. This kind of disturbance can be diagnosed by using
      morphometric tools to study morphological patterns at different hierarchical
      levels and evaluate canalization, developmental stability, integration,
      modularity, and allometry. We assess the effect of urbanization on phenotypic
      variation in the common wall lizard (Podarcis muralis) by using geometric
      morphometrics to assess disturbance to head shape development. The head shapes of
      urban lizards were more variable and less symmetric, suggesting that urban living
      is more likely to disturb development. Head shape variation was congruent within
      and across individuals, which indicated that canalization and developmental
      stability are two related phenomena in these organisms. Furthermore, urban
      lizards exhibited smaller mean head sizes, divergent size-shape allometries, and
      increased deviation from within-group allometric lines. This suggests that
      mechanisms regulating head shape allometry may also be disrupted. The integrated
      evaluation of several measures of developmental instability at different
      hierarchical levels, which provided in this case congruent results, can be a
      powerful methodological guide for future studies, as it enhances the detection of
      environmental disturbances on phenotypic variation and aids biological
      interpretation of the results.

PMID- 25560553
TI  - A neutral theory for interpreting correlations between species and genetic
      diversity in communities.
AB  - Spatial patterns of biological diversity have been extensively studied in ecology
      and population genetics, because they reflect the forces acting on biodiversity.
      A growing number of studies have found that genetic (within-species) and species
      diversity can be correlated in space (the so-called species-gene diversity
      correlation [SGDC]), which suggests that they are controlled by nonindependent
      processes. Positive SGDCs are generally assumed to arise from parallel responses
      of genetic and species diversity to variation in site size and connectivity.
      However, this argument implicitly assumes a neutral model that has yet to be
      developed. Here, we build such a model to predict SGDC in a metacommunity. We
      describe how SGDC emerges from competition within sites and variation in
      connectivity and carrying capacity among sites. We then introduce the formerly
      ignored mutation process, which affects genetic but not species diversity. When
      mutation rate is low, our model confirms that variation in the number of migrants
      among sites creates positive SGDCs. However, when considering high mutation
      rates, interactions between mutation, migration, and competition can produce
      negative SGDCs. Neutral processes thus do not always contribute positively to
      SGDCs. Our approach provides empirical guidelines for interpreting these novel
      patterns in natura with respect to evolutionary and ecological forces shaping
      metacommunities.

PMID- 25560554
TI  - The limited contribution of reciprocal gene loss to increased speciation rates
      following whole-genome duplication.
AB  - Hybrid incompatibilities contribute to reproductive isolation between species,
      allowing them to follow independent evolutionary trajectories. Since hybrid
      incompatibilities are by definition deleterious, they cannot be selected for
      directly and must arise as a by-product of evolutionary divergence. Divergent
      resolution of duplicate genes, a special case of Dobzhansky-Muller
      incompatibilities, is one mechanism by which hybrid incompatibility can evolve.
      Following whole-genome duplication, loss of gene copies could possibly increase
      the opportunity for divergent resolution and, hence, the evolution of hybrid
      incompatibilities. However, divergent resolution can take place only when
      populations are isolated in allopatry; genes lost within a species cannot
      contribute to future speciation. Furthermore, nearly complete allopatry is
      necessary for passive divergent resolution. Using mathematical models, we
      demonstrate that these two factors severely impede the ability of divergent
      resolution alone to increase speciation rates, except under very particular
      conditions. Instead, we find that the population dynamics of diverging lineages
      dominate this process, leading to a larger role for ecology relative to genetics
      in the origin of new species, even by passive mechanisms. Divergent resolution of
      duplicate genes might increase speciation rates in some clades at some times, but
      our results indicate that it alone is unlikely to account for the
      macroevolutionary success of polyploid clades.

PMID- 25560555
TI  - A metric for quantifying the oscillatory tendency of consumer-resource
      interactions.
AB  - The oscillatory tendency of consumer-resource interactions is a key determinant
      of food-web persistence. Here, we develop a metric for quantifying oscillatory
      tendency that scales the positive feedback effects of saturating functional
      responses with the negative feedback effects of self-limitation. We use this
      metric to predict the oscillatory tendency of a pairwise interaction, tritrophic
      chain, and tritrophic web. This framework yields two key predictions. First, the
      oscillatory tendency of any food web increases with the number of trophic links
      with long handling times regardless of the magnitude of attack rates. Attack
      rates influence oscillatory tendency only when handling times are short. Second,
      the realized oscillatory tendency of a trophic link depends on how the product of
      the attack rate and handling time scales with the strength of self-limitation.
      Importantly, our metric allows calculations of the critical self-limitation
      strength at which a consumer-resource interaction moves from stable to
      oscillatory dynamics. Our data analysis reveals that the majority (77%) of
      interactions involve low attack rates and handling times, requiring only a modest
      level of self-limitation to suppress oscillations. Only 23% of the interactions
      exhibit a strong oscillatory tendency, consistent with previous findings, based
      on time-series data, that 30% of consumer-resource interactions in nature exhibit
      oscillations.

PMID- 25560556
TI  - The effects of the avoidance of infectious hosts on infection risk in an insect
      pathogen interaction.
AB  - In many animal host-pathogen interactions, uninfected hosts either avoid or are
      attracted to infected conspecifics, but understanding how such behaviors affect
      infection risk is difficult. In experiments, behaviors are often eliminated
      entirely, which allows demonstration that a behavior affects risk but makes it
      impossible to quantify effects of individual behaviors. In models, host behaviors
      have been studied using ordinary differential equations, which can be easily
      analyzed but cannot be used to relate individual behaviors to risk. For many
      insect baculoviruses, however, quantifying effects of behavior on risk is
      straightforward because transmission occurs when host larvae accidentally consume
      virus-contaminated foliage. Moreover, increases in computing power have made it
      possible to fit complex models to data. We therefore used experiments to quantify
      the behavior of gypsy moth larvae feeding on oak leaves contaminated with virus
      infected cadavers, and we tested for effects of cadaver-avoidance behavior by
      fitting stochastic simulation models to our data. The models that best explain
      the data include cadaver avoidance, and comparison of models that do and do not
      include cadaver avoidance shows that this behavior substantially reduces
      infection risk. Our work demonstrates that host behaviors that affect exposure
      risk play a key role in baculovirus transmission and adds to the growing
      consensus that host behavior can strongly alter pathogen transmission rates.

PMID- 25560557
TI  - Nonrandom patterns of genetic admixture expose the complex historical hybrid
      origin of unisexual leaf beetle species in the genus Calligrapha.
AB  - Many unisexual animal lineages supposedly arose from hybridization. However,
      support for their putative hybrid origins mostly comes from indirect
      methodologies, which are rarely confirmatory. Here we provide compelling data
      indicating that tetraploid unisexual Calligrapha are true genetic mosaics
      obtained via analysis of mitochondrial DNA (mtDNA) and allelic variation and
      coalescence times for three single-copy nuclear genes (CPS, HARS, and Wg) in five
      of six unisexual Calligrapha and a representative sample of bisexual species.
      Nuclear allelic diversity in unisexuals consistently segregates in the gene pools
      of at least two but up to three divergent bisexual species, interpreted as
      putative parentals of interspecific hybridization crosses. Interestingly, their
      mtDNA diversity derives from an additional yet undiscovered older evolutionary
      lineage that is possibly the same for all independently originated unisexual
      species. One possibly extinct species transferred its mtDNA to several
      evolutionary lineages in a wave of hybridization events during the Pliocene,
      whereby descendant species retained a polymorphic mtDNA constitution. Recent
      hybridizations, in the Pleistocene and always involving females with the old
      introgressed mtDNA, seemingly occurred in the lineages leading to unisexual
      species, decoupling mtDNA introgression (and inferences derived from these data,
      such as timing and parentage) from subsequent acquisition of the new reproductive
      mode. These results illuminate an unexpected complexity in possible routes to
      animal unisexuality, with implications for the interpretation of ancient
      unisexuality. If the origin of unisexuality requires a mechanism where (1)
      hybridization is a necessary but insufficient condition and (2) multiple bouts of
      hybridization involving more than two divergent lineages are required, then the
      origins of several classical unisexual systems may have to be reassessed.

PMID- 25560558
TI  - Morphological and behavioral evidence of Batesian mimicry in nestlings of a
      lowland Amazonian bird.
AB  - Because predation is the main cause of avian nest failure, selection should favor
      strategies that reduce the probability of nest predation. We describe apparent
      Batesian mimicry in the morphology and behavior of a Laniocera hypopyrra
      nestling. On hatching, the nestling had a distinctive bright orange color and
      modified feathers all over its body, and 6 days after hatching, it started to
      move its head very slowly from side to side (in a "caterpillar" movement) when
      disturbed. These traits gave it a resemblance to a hairy, aposematic caterpillar.
      This species has a long nestling period for its size (20 days), perhaps due to
      slow provisioning rates (about one feeding per hour). We argue that the slow
      growth rate, combined with high nest predation, favors the evolution of
      antipredation mechanisms such as the unique morphological and behavioral
      characteristics of L. hypopyrra nestlings.

PMID- 25560559
TI  - Choice of resolution by functional trait or taxonomy affects allometric scaling
      in soil food webs.
AB  - Belowground organisms often display a shift in their mass-abundance scaling
      relationships due to environmental factors such as soil chemistry and atmospheric
      deposition. Here we present new empirical data that show strong differences in
      allometric scaling according to whether the resolution at the local scale is
      based on a taxonomic or a functional classification, while only slight
      differences arise according to soil environmental conditions. For the first time,
      isometry (an inverse 1:1 proportion) is recognized in mass-abundance
      relationships, providing a functional signal for constant biomass distribution in
      soil biota regardless of discrete trophic levels. Our findings are in contrast to
      those from aquatic ecosystems, in that higher trophic levels in soil biota are
      not a direct function of increasing body mass.

PMID- 25560560
TI  - Discriminating selection on lateral plate phenotype and its underlying gene,
      Ectodysplasin, in threespine stickleback.
AB  - When a signature of natural selection is discovered on a gene that is pleiotropic
      or in tight linkage with other genes, it is challenging to determine which of the
      affected phenotypes is under selection. One way to make progress is to employ
      methods for analyzing natural selection on correlated traits, including both
      genotype and phenotype. We used this approach in threespine stickleback to
      estimate selection on a rapidly evolving trait, lateral armor plates, while
      controlling for variation at its major underlying gene, Ectodysplasin (Eda), and
      vice versa. This allowed for independent estimates of selection on lateral plates
      and on Eda via other traits. Previously, we demonstrated allele frequency changes
      at Eda in a pond experiment. Here we show that this resulted from selection on
      both plates and on Eda, implying additional selection on other phenotypic traits
      affected by the same gene. This represents the first evidence for direct
      selection on lateral plates independent of selection on the Eda locus and
      highlights the value of measuring selection on both phenotypes and genotypes in
      studies of adaptation.

PMID- 25560561
TI  - A graphical-mechanistic approach to spatial resource competition.
AB  - Ecological communities are structured by processes operating at multiple spatial
      scales, which results in an often daunting complexity. Here we present a simple
      graphical theory to study the interaction of two fundamental community processes:
      resource competition at the local scale and dispersal at the regional scale. We
      consider a metacommunity model with two habitat patches in which consumer species
      compete for a spatially distributed resource. We introduce a graphical
      construction of the equilibrium metacommunity composition, analogous to
      traditional competition theory for two resources. As in the nonspatial case, the
      zero net growth isoclines (ZNGIs) play a central role in the analysis. We show
      that a consumer species' ZNGI depends on its dispersal characteristics, and this
      dependence leads to a unification of various dispersal-based coexistence
      mechanisms. We illustrate this unification using four specific mechanisms:
      species-specific dispersal rates, spatially asymmetric dispersal, resource
      dependent dispersal, and competition between habitat specialists and generalists.

PMID- 25560562
TI  - Evolutionary and ecological consequences of multiscale variation in pollen
      receipt for seed production.
AB  - Variation in resource availability can select for traits that reduce the negative
      impacts of this variability on mean fitness. Such selection may be particularly
      potent for seed production in flowering plants, as they often experience
      variation in pollen receipt among individuals and among flowers within
      individuals. Using analytically tractable models, we examine the optimal
      allocations for producing ovules, attracting pollen, and maturing seeds in
      deterministic and stochastic pollen environments. In deterministic environments,
      the optimal strategy attracts sufficient pollen to fertilize every ovule and
      mature every zygote into a seed. Stochastic environments select for allocations
      proportional to the risk of seed production being limited by zygotes or seed
      maturation. When producing an ovule is cheap and maturing a seed is expensive,
      among-plant variation selects for attracting more pollen at the expense of
      producing fewer ovules and having fewer resources for seed maturation. Despite
      this increased allocation, such populations are likely to be pollen limited. In
      contrast, within-plant variation generally selects for an overproduction of
      ovules and, to a lesser extent, pollen attraction. Such populations are likely to
      be resource limited and exhibit low seed-to-ovule ratios. These results highlight
      the importance of multiscale variation in the evolution and ecology of resource
      allocations.

PMID- 25560564
TI  - 2014 American Society of Naturalists awards.

PMID- 25560566
TI  - HLA Correlates of Long-Term Survival in Vertically Infected HIV-1-Positive
      Adolescents in Harare, Zimbabwe.
AB  - African infants with vertically acquired HIV infection progress rapidly, with
      only 50% surviving beyond 2 years in the absence of treatment. Despite this high
      initial mortality, recent reports describe a substantial burden of older children
      living with untreated vertically acquired HIV infection in Southern Africa. The
      immunological and genetic factors associated with long-term survival following
      vertical infection are poorly understood. We performed medium-to-high resolution
      HLA typing on DNA samples obtained from a cohort of presumed vertically HIV-1
      infected children and age-matched uninfected controls in Harare, Zimbabwe.
      Overall, 93 HLA class I alleles were detected in the study population with a
      significant enrichment of HLA-C*08:02 and -C*08:04 in the HIV-1-infected long
      term survivor group. Conversely, HLA-A*02:01, A*34:02, and -B*58:02 were
      overrepresented in the uninfected control group. Our data indicate that HLA
      alleles may have differential effects against HIV acquisition and disease
      progression in vertical HIV-1 infection. 

PMID- 25560565
TI  - Stage-dependent benefits and risks of pimobendan in mice with genetic dilated
      cardiomyopathy and progressive heart failure.
AB  - BACKGROUND AND PURPOSE: The Ca(2+) sensitizer pimobendan is a unique inotropic
      agent that improves cardiac contractility with less of an increase in oxygen
      consumption and potentially fewer adverse effects on myocardial remodelling and
      arrhythmia, compared with traditional inotropes. However, clinical trials report
      contradictory effects of pimobendan in patients with heart failure (HF). We
      provide mechanistic experimental evidence of the efficacy of pimobendan using a
      novel mouse model of progressive HF. EXPERIMENTAL APPROACH: A knock-in mouse
      model of human genetic dilated cardiomyopathy, which shows a clear transition
      from compensatory to end-stage HF at a fixed time during growth, was used to
      evaluate the efficacy of pimobendan and explore the underlying molecular and
      cellular mechanisms. KEY RESULTS: Pimobendan prevented myocardial remodelling in
      compensated HF and significantly extended life span in both compensated and end
      stage HF, but dose-dependently increased sudden death in end-stage HF. In
      cardiomyocytes isolated from end-stage HF mice, pimobendan induced triggered
      activity probably because of early or delayed afterdepolarizations. The L-type
      Ca(2+) channel blocker verapamil decreased the incidence of triggered activity,
      suggesting that this was from over-elevated cytoplasmic Ca(2+) through increased
      Ca(2+) entry by PDE3 inhibition under diminished sarcoplasmic reticulum Ca(2+)
      reuptake and increased Ca(2+) leakage from sarcoplasmic reticulum in end-stage
      HF. CONCLUSIONS AND IMPLICATIONS: Pimobendan was beneficial regardless of HF
      stage, but increased sudden cardiac death in end-stage HF with extensive
      remodelling of Ca(2+) handling. Reduction of cytoplasmic Ca(2+) elevated by PDE3
      inhibition might decrease this risk of sudden cardiac death.

PMID- 25560567
TI  - Nurses', midwives' and key stakeholders' experiences and perceptions of a scope
      of nursing and midwifery practice framework.
AB  - AIM: This paper reports on the qualitative findings from a national review of a
      nursing and midwifery scope of practice framework. BACKGROUND: Scope of
      professional practice frameworks offers a system of rules and principles to
      regulate its members and demonstrate its responsibility to society. Key issues in
      reviewing the scope of practice include notions of specialist and advanced
      practice, accountability, autonomy, competence, supervision, continuing
      professional development and delegation. Evaluation of scope of practice
      frameworks has particular application value to nurses, midwives, regulatory
      bodies and healthcare employers across the globe. DESIGN: A mixed methods
      approach was used. This included a national survey of nurses and midwives and
      focus groups and interviews with key stakeholders. The qualitative data are
      reported in this paper. METHODS: Focus groups and interviews were conducted among
      a convenience purposive sample of key stakeholders, including nurses and midwives
      working in the widest range of services and settings in 2014. The participants
      contributed to thirteen focus groups and thirteen interviews. FINDINGS: Six
      global themes, as follows: Evolution of the nursing and midwifery professions and
      practice; Scope of practice: understanding and use; Expanding scope of practice;
      Professional competence; Practice setting and context; Reflections on the current
      framework. CONCLUSION: Practitioners understand the scope of professional
      practice and while some see it as empowering others see it as potentially
      restrictive. Nurses and midwives are generally willing to expand their scope of
      practice and see it as resulting in improved patient care, improvement in overall
      quality of standards and increased job satisfaction.

PMID- 25560568
TI  - Selenitetriglycerides-Redox-active agents.
AB  - BACKGROUND: Human prostate cancer (hPCa) is the most commonly diagnosed cancer in
      elderly men and is the second leading cause of male cancer death. Data from
      epidemiological, eco-environmental, nutritional prevention and clinical trials
      suggest that selenium Se(IV) can prevent prostate cancer. Selol, a new organic
      semisynthetic derivative of Se(IV), is a mixture of selenitetriglycerides. This
      mixture is non-toxic and non-mutagenic, and after po treatment - 56-times less
      toxic (in mice) than sodium selenite. It exhibits strong anti-cancer activity in
      vitro in many cancer cell lines and can overcome the cell resistance to
      doxorubicin. Selol seems a promising compound for prostate cancer therapy.
      MATERIALS AND METHODS: The aim of the present study is the evaluation of Selol's
      influence on intracellular redox state (Eh) of prostatic tumors and the liver in
      androgen-dependent hPCa-bearing mice, and extracellular redox state in serum of
      these mice. RESULTS AND CONCLUSIONS: The anticancer activity of Selol involves
      perturbation of the redox regulation in the androgen dependent hPCa (LNCaP)
      cells, but not in healthy cells. After Selol treatment, intracellular Eh has
      increased in tumors from -223 mV to -175 mV, while in serum it has decreased (-82
      mV vs -113 mV). It shows significant changes Eh in the extra- and intracellular
      environment. The difference decreases from 141 mV to 62 mV. The changes suggest
      that a tumor cell was probably directed toward apoptosis. This is exemplified in
      a significant decrease in cancer tumor mass by approx. 17% after the three weeks
      of Selol administration.

PMID- 25560569
TI  - Analgesic activity of new 8-methoxy-1,3-dimethyl-2,6-dioxo-purin-7-yl derivatives
      with carboxylic, ester or amide moieties.
AB  - BACKGROUND: The previous studies in a group of 4-arylpiperazinylalkyl derivatives
      of purine-2,6-dione and several other heterocyclic systems revealed their
      analgesic properties. In an effort to establish new analgesic agents we designed
      and synthesized a series of new 8-methoxy-1,3-dimethyl-2,6-dioxo-purin-7-yl
      derivatives with terminal carboxylic, ester or amide moieties. METHODS: The
      obtained compounds were evaluated pharmacologically in two in vivo models: the
      writhing syndrome and the formalin tests. The influence of the investigated
      compounds on the phosphodiesterase (PDE) activity was also determined. RESULTS:
      Majority of the tested compounds showed significant analgesic activity. The
      strongest analgesic and anti-inflammatory effect were observed for benzylamide
      (10) and 4-phenylpiperazinamide (11-14) derivatives which were more active than
      acetylic acid used as a reference drug (up to 23 and 36 fold increase in activity
      in writhing and formalin test, respectively). Several active compounds stronger
      than theophylline inhibited the phosphodiesterase activity. CONCLUSION: The
      present study revealed that the presented compounds are new class of analgesic
      and anti-inflammatory agents and are worthy of the further evaluation regarding
      to their pharmacological properties.

PMID- 25560570
TI  - H2S donors attenuate diabetic nephropathy in rats: Modulation of oxidant status
      and polyol pathway.
AB  - BACKGROUND: Sulfurous mineral water and its main active ingredient sodium
      hydrosulfide (NaHS) are major sources of H2S. The present study aimed to explore
      their protective effect on one of the serious long-term complications of
      diabetes; diabetic nephropathy. METHODS: Sulfurous mineral water (as drinking
      water), NaHS (14 MUmol/kg/day; ip), and gliclazide (10mg/kg; po) were
      administered daily for 6 weeks to streptozotocin (STZ)-diabetic rats. RESULTS:
      STZ-induced diabetes was associated with body weight reduction, hyperglycemia,
      overproduction of glycated hemoglobin, as well as decline in serum insulin, C
      peptide, and insulin like growth factor-I. Besides, diabetes impaired kidney
      functions and imposed oxidative and nitrosative stress as manifested by elevated
      contents of renal thiobarbituric acid reactive substances and nitric oxide,
      parallel to reduced glutathione content. These deleterious effects were
      antagonized by sulfurous water and to a better extent by NaHS. Activities of
      myeloperoxidase and sorbitol dehydrogenase were not altered by STZ or any of the
      treatments. However, STZ-induced diabetes was accompanied by an increment of
      aldose reductase which was only mitigated by gliclazide and NaHS.
      Histopathological examination of kidney sections corroborated the biochemical
      findings. CONCLUSION: This study suggests a novel therapeutic approach for
      diabetic nephropathy using H2S donors.

PMID- 25560571
TI  - Multifactorial effects of vildagliptin added to ongoing metformin therapy in
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: To assess the efficacy of a vildagliptin and metformin combination
      therapy to a metformin monotherapy in type 2 diabetes mellitus patients. METHODS:
      Sixty-one patients with diabetes inadequately controlled by a metformin
      monotherapy were randomized to treatment with a combination therapy of
      vildagliptin 100mg and a metformin versus metformin monotherapy. This was a 12
      week randomized parallel group study. During the study we assessed parameters of
      glycemic and lipid metabolism as well as the treatment effects on the release of
      proinflammatory and antiinflammatory cytokines. RESULTS: Compared with baseline
      values we observed a significant improvement of glycaemic parameters such as
      HbA1c, FPG, PPG, FPI, HOMA-IR and HOMA-beta index as well as decrease of TCh, TG
      and LDL and an increase of HDL with the greatest extent of vildagliptin plus a
      low-dose metformin therapy group. A metformin combination therapy significantly
      decreased such inflamation parameters as hs-CRP, ox-LDL, TNF-alpha and IL-1beta
      levels relative to monotherapies. All treatments were well tolerated and there
      was no incidence of hypoglycaemia. CONCLUSIONS: Vildagliptin added to an ongoing
      metformin therapy allows to achieve better metabolic control parameters in
      comparison with a metformin monotherapy and the combination treatment is well
      tolerated and has a low risk of serious adverse effects.

PMID- 25560572
TI  - HMG-COA reductase inhibitors: An opportunity for the improvement of imatinib
      safety. An experimental study in rat pulmonary hypertension.
AB  - BACKGROUND: Co-administration of statin with imatinib is thought to result in
      greater improvement in pulmonary arterial hypertension (PAH) than imatinib
      treatment alone, and hence may allow greater effectiveness of imatinib therapy at
      lower doses. METHODS: The effects of imanitib at dose of 20 and 50mg/kg bw given
      together with rosuvastatin or simvastatin were investigated with respect to right
      ventricle pressure (RVP), arterial blood pressure and right ventricle hypertrophy
      (RVH) in experimental monocrotaline (MCT)-induced pulmonary hypertension.
      Fourteen days after MCT injection, male rats were treated orally for another 14
      days with imatinib, statin or a combination of the two. RESULTS: Concurrent
      administration of statin (lipophilic simvastatin, hydrophilic rosuvastatin) and
      higher dose imatinib reversed the MCT-induced increase in RVP more than each drug
      alone and decreased RV hypertrophy (RV/LV+S ratio), significantly. The increased
      RVP and RV hypertrophy was found to be reversed when a lower dose of imatinib was
      co-administered with rosuvastatin or simvastatin. CONCLUSIONS: Statins may
      intensify the beneficial effects of imatinib in PAH, which may be due to the
      additional influence of statin on the decrease of platelet-derived growth factor
      (PDGF)-induced effects. These properties allow the dose of imatinib used in PAH
      treatment to be reduced and thereby might improve its safety profile.

PMID- 25560573
TI  - Impact of sparfloxacin on melanogenesis and antioxidant defense system in normal
      human melanocytes HEMa-LP - An in vitro study.
AB  - BACKGROUND: Fluoroquinolones are a group of broad spectrum bactericidal
      antibiotics used to treat various infections of urinary and respiratory systems,
      as well as in ophthalmology and dermatology. This class of antibiotics causes
      toxic effects directed to pigmented tissues, what introduces a serious limitation
      to their use. The aim of this work was to examine the impact of sparfloxacin on
      melanogenesis and the antioxidant defense system in normal human epidermal
      melanocytes, adult, lightly pigmented (HEMa-LP). METHODS: The effect of
      sparfloxacin on cell viability was determined by WST-1 assay; melanin content,
      tyrosinase activity as well as antioxidant enzymes activity were measured
      spectrophotometrically. RESULTS: Sparfloxacin induced the concentration -
      dependent loss in melanocytes viability. The value of EC50 was determined to be
      ~0.25 mM. Sparfloxacin inhibited tyrosinase activity and reduced the melanin
      content in human melanocytes. To study the antioxidant defense system in
      melanocytes, the activities of superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GPx) in cells exposed to sparfloxacin were determined. It
      was observed that sparfloxacin caused depletion of the antioxidant status of
      melanocytes. CONCLUSIONS: The observed sparfloxacin-dependent inhibition of
      melanogenesis and changes of antioxidant enzymes activities in human melanocytes
      give a new insight into the mechanism of fluoroquinolones toxicity directed to
      pigmented tissues.

PMID- 25560574
TI  - Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of nifedipine in
      rats: Possible role of P-gp and CYP3A4 inhibition by HMG-CoA reductase
      inhibitors.
AB  - BACKGROUND: This study aimed to investigate the effects of HMG-CoA reductase
      inhibitors on the pharmacokinetics of nifedipine in rats. METHODS: We determined
      the pharmacokinetic parameters of nifedipine and dehydronifedipine in rats after
      oral and intravenous administration of nifedipine without and with HMG-CoA
      reductase inhibitors. We evaluated the effect of HMG-CoA reductase inhibitors on
      the activity of P-glycoprotein (P-gp) and cytochrome P450 (CYP)3A4. RESULTS:
      Atorvastatin, fluvastatin, pravastatin and simvastatin inhibited CYP3A4
      activities; inhibitory concentration (IC50) values were 47.0, 5.2, 15.0 and 3.3
      MUM, respectively. Simvastatin and fluvastatin increased the cellular uptake of
      rhodamine-123. The area under the plasma concentration-time curve (AUC0-infinity)
      and the peak plasma concentration (Cmax) of oral nifedipine were significantly
      increased by fluvastatin and simvastatin, respectively, compared to control
      group. The total body clearance (CL/F) of nifedipine after oral administration
      with fluvastatin and simvastatin were significantly decreased compared to those
      of control. The metabolite-parent AUC ratio (MR) of nifedipine with fluvastatin
      and simvastatin were significantly decreased, which suggested that fluvastatin
      and simvastatin inhibited metabolism of nifedipine, respectively. The AUC0
      infinity of intravenouse nifedipine with fluvastatin and simvastatin was
      significantly higher than that of the control group. CONCLUSION: The increased
      bioavailability of nifedipine may be mainly due to inhibition of both P-gp in the
      small intestine and CYP3A subfamily-mediated metabolism of nifedipine in the
      small intestine and/or in the liver and to the reduction of the CL/F of
      nifedipine by fluvastatin and simvastatin.

PMID- 25560575
TI  - Dezocine prevents sufentanil-induced cough during general anesthesia induction: A
      randomized controlled trial.
AB  - BACKGROUND: Opioid-induced cough during induction of general anesthesia is a
      common phenomenon. Dezocine, a partial MU-receptors agonist and kappa-receptors
      antagonist, has been documented effectively suppressing fentanyl-induced cough in
      general anesthesia induction. However, the effect of dezocine on sufentanil
      induced cough is still unknown. METHODS: A total of 370 patients (American
      Society of Anesthesiologists physical status I-II), aged 18-70 years, undergoing
      elective surgery, were randomly divided into a control group (group C) and a
      dezocine group (group D) (n=185 in each group). Patients received dezocine
      0.1mg/kg or an equal volume of 0.9% normal saline 2 min prior to intravenous
      sufentanil (0.5 MUg/kg). The incidence and reflex degree of cough in patients
      were evaluated within 2 min after the injection of sufentanil in anesthesia
      induction period. RESULTS: No patient in group D had cough and 59 patients in
      group C had cough (severity of cough: mild, 7%; moderate, 11.4%; severe, 13.5%).
      The occurrence and reflex degree of cough in group D was significantly lower than
      that in group C (P=0.000). The highest heart rate (HR) and invasive blood
      pressure (IBP) values were higher in group C than those in group D (P<0.01)
      within 2 min after sufentanil administration, althought these values remained
      within safe limits. CONCLUSION: The results of current study suggest that
      administration of Dezocine 0.1mg/kg may effectively prevent the occurrence and
      reflex degree of sufentanil-induced irritating cough in general anesthesia
      induction in patients.

PMID- 25560576
TI  - Taking aim at a dynamic target: Noscapinoids as microtubule-targeted cancer
      therapeutics.
AB  - Noscapine and its synthetic derivatives called noscapinoids have been shown to
      possess potential anticancer properties. These alkaloids target microtubules and
      inhibit cell proliferation. Noscapinoids are microtubule poisons that induce
      minor alterations in the innate dynamic instability of microtubules leading to
      mitotic arrest and cell death. Over the past decade, a number of noscapine
      derivatives have been synthesized that, compared to the parent compound, show
      superior anticancer potential, enhanced tumor specificity and tumor regression,
      and little or no toxicity to normal tissues. Based on their successive synthetic
      modifications at different points in the scaffold structure of noscapine, aided
      by computational design and structure-activity relationship studies, the
      derivatives of noscapine have been classified into different "generations" based
      on modifications. Several studies have reported the potential to develop
      noscapinoids as anticancer drugs. Increasing their tumor specificity - either
      through antibody conjugation or nanoparticle-based carriers - may facilitate the
      progression of maytansinoid-based cancer drugs to the clinic. 

PMID- 25560577
TI  - Antinociceptive properties of N-Mannich bases derived from 3-substituted
      pyrrolidine-2,5-dione in the formalin model of persistent pain in mice.
AB  - BACKGROUND: Accumulated data indicate that anticonvulsants possess
      antinociceptive properties in rodent pain models. In view of the anticonvulsant
      activity demonstrated previously among N-Mannich bases derived from 3-mono- (1-6)
      and 3,3-disubstituted pyrrolidine-2,5-diones (7-14) their analgesic activity has
      been investigated in the formalin model of tonic pain in mice. METHODS: The
      compounds 1-14 were tested at doses equal to the respective ED50 values obtained
      earlier in the MES test. 0.5% formalin solution was given as intraplantar
      injections into the hind paw of the mouse and the duration of the nocifensive
      response was counted in drug-treated and vehicle-treated animals in the acute and
      the late phases of the test. RESULTS: A significant antinociceptive activity was
      observed for majority of the compounds. In the first phase of the test all the
      active compounds, except for 9-11, reduced the duration of the licking response
      up to 88% (compounds 2 and 6; p<0.001). In the late phase the 1-3, 5, 6, 9 and 14
      were the most effective agents and their analgesic activities ranged from 92 to
      100%. CONCLUSIONS: The results of the research indicate that some of the
      investigated compounds reduced effectively either both phases of the test or were
      able to attenuate pain during only the acute or late phase of the formalin test.
      These properties, which are particularly strong in case of the compounds 1-3, 5,
      6, 9 and 14, might be relevant for the development of novel analgesic-active
      compounds and their possible use in neuropathic pain syndromes.

PMID- 25560578
TI  - Effects of incretin agonists on endothelial nitric oxide synthase expression and
      nitric oxide synthesis in human coronary artery endothelial cells exposed to
      TNFalpha and glycated albumin.
AB  - BACKGROUND: There have been a number of beneficial effects of incretin agonists
      on the cardiovascular system. Glycated albumin (GA) and tumor necrosis factor
      (TNFalpha) may lead to endothelial dysfunction. Due to reports of
      cardioprotective effects of incretin agonist, we wanted to determine if GLP-1 and
      exendin-4 can reverse diminished production of nitric oxide (NO) after treatment
      with TNFalpha and GA. The objective of our experiment was to study the
      interaction between incretin agonists and proinflammatory substances like
      TNFalpha and GA on production of NO in HCAEC. METHODS: Human vascular endothelial
      cells from the coronary artery (HCAEC) were used. The mRNA expression and protein
      level of endothelial nitric oxide synthase (eNOS) and inducible (iNOS) were
      quantified. NO production was measured in cells using DAF-FM/DA and flow
      cytometry. RESULTS: TNFalpha (10 ng/mL) decreased eNOS: mRNA by 90% and protein
      level by 31%. TNFalpha also decreased NO by 33%. GA (500 MUg/mL) neither affected
      eNOS expression nor the protein level, but inhibited nearly all formation of NO
      in endothelium. GLP-1 (100 nM) and exendin-4 (1 and 10nM) decreased the amount of
      NO compared to control. Incubation of HCAEC with TNFalpha and incretin agonists
      did not change or moderately reduce the amount of NO compared to TNFalpha alone.
      CONCLUSIONS: TNFalpha and GA decrease production of NO in HCAEC, presumably by
      inducing reactive oxygen species or eNOS uncoupling. Incretin agonists in tested
      concentrations in the presence of l-arginine were not able to reverse this effect
      and instead led to a further reduction in NO production.

PMID- 25560579
TI  - Pioglitazone prevents morphine antinociceptive tolerance via ameliorating
      neuroinflammation in rat cerebral cortex.
AB  - BACKGROUND: Opioid induced neuroinflammation is shown to be implicated in opioid
      analgesic tolerance development. In the present study the effect of pioglitazone
      on morphine-induced tolerance and neuroinflammation in the cerebral cortex of the
      rat was investigated. MATERIALS AND METHODS: Various groups of rats received
      morphine (10mg/kg; ip) and vehicle (po), or morphine (10mg/kg) and pioglitazone
      (20 or 40 mg/kg; po) once a day for 17 days. In order to determine the possible
      involvement of PPAR-gamma in the pioglitazone effect, one group of rats received
      PPAR-gamma antagonist, GW-9662 (2mg/kg; sc), and pioglitazone (40 mg/kg) and
      morphine once daily for 17 days. Nociception was assessed using a tail flick
      apparatus and the percentage of the maximal possible effect was calculated as
      well. On 18th day, 2h after the last morphine injection, the cerebral cortex of
      the animals were harvested and the tissue levels of tumour necrosis factor alpha,
      interleukin-1beta, interleukin-6, interleukin-10 and nuclear factor-kappa B
      activity were determined. RESULTS: Co-administration of pioglitazone (40 mg/kg)
      with morphine not only attenuated morphine-induced tolerance, but also prevented
      the up-regulation of pro-inflammatory cytokines (tumour necrosis factor alpha,
      interleukin-1beta, interleukin-6) and nuclear factor-kappa B activity in the rat
      cerebral cortex. Moreover, GW-9662 (2mg/kg) administration 30 min before
      pioglitazone, antagonized the above mentioned pioglitazone-induced effects.
      CONCLUSION: It is concluded that oral administration of pioglitazone attenuates
      morphine-induced tolerance. This effect of pioglitazone may be, at least in part,
      due to its anti-inflammatory property which suppressed the cortical pro
      inflammatory cytokine and inhibited of nuclear factor-kappa B activity.

PMID- 25560580
TI  - The MCP-1, CCL-5 and SDF-1 chemokines as pro-inflammatory markers in generalized
      anxiety disorder and personality disorders.
AB  - INTRODUCTION: The co-occurrence of generalized anxiety disorder and personality
      disorders suggests the existence of association between the neurobiological
      predispositions leading to the development of these disorders and activation of
      cytokine system. Pro-inflammatory chemokines such as CCL-5/RANTES (regulated upon
      activation normal T cell expressed and secreted) and CXCL12/SDF-1 (stromal
      derived factor) play an important role in immune response. METHODS: A total of
      160 participants were enrolled in the study, 120 of whom comprised the study
      group (people with the dual diagnosis of personality disorder and generalized
      anxiety disorder). The mean age was 41.4 +/- 3.5 years (range: 20-44 years). The
      control group consisted of 40 healthy individuals in the mean age of 40.8 +/- 3.1
      years (range: 20-43 years). A blood sample was collected from each participant
      and the plasma levels of the CCL-2/MCP-1 (monocyte chemoattractant protein-1),
      RANTES and SDF-1 chemokines were determined by ELISA. RESULTS: Increased levels
      of MCP-1 and SDF-1 were found both in women and in men versus the control group
      for all types of personality disorders. The levels of CCL-5 in men were
      significantly increased versus the control group and significantly higher in
      women than in men. Neither women nor men with avoidant or obsessive-compulsive
      personality disorder showed any significant differences in MCP-1 or SFD-1 levels.
      In subjects with borderline personality disorder, the levels of the study
      chemokines were higher in women than in men. CONCLUSIONS: Our study has shown the
      need for determination of proinflammatory interleukins which are considered as
      biomarkers of personality disorders and generalized anxiety disorders.

PMID- 25560581
TI  - Mechanisms of morphine-venlafaxine interactions in diabetic neuropathic pain
      model.
AB  - BACKGROUND: we investigated the possible mechanisms involved in the interactions
      of venlafaxine (VFX), a selective serotonin and noradrenaline reuptake inhibitor,
      and morphine (MRF), an opioid receptor agonist, after acute and chronic VFX
      treatment in diabetic neuropathic pain model (DNPM). METHODS: The studies were
      performed on male rats. The changes in nociceptive thresholds were determined by
      using mechanical stimuli (the Randall-Selitto and the von Frey tests). Diabetes
      was induced by intramuscular administration of streptozotocin. In order to
      investigate the mechanism of interaction, animals were also pretreated with
      naloxone (NLX), a nonselective opioid antagonist, yohimbine (YOH), a nonselective
      alpha2-adrenergic antagonist, and p-chloroamphetamine (PCA), a neurotoxin that
      destroys serotonergic neurons. The MU-opioid receptors' density was determined
      with the use of radioligand binding assay. RESULTS: VFX potentiated
      antinociceptive action of MRF after acute administration of VFX and this effect
      was decreased by pretreatment of NLX, YOH and PCA. On the contrary, VFX
      administered for 21 days prior to MRF significantly decreased the analgesic
      action of MRF; this effect was augmented only after YOH pretreatment. Also, 21
      days administration of VFX caused decreasing tendency in the number of MU-opioid
      receptors in the brain stem. CONCLUSIONS: The results of our study show that
      single administration of VFX potentiates antinociceptive action of morphine in
      DNPM. This effect is probably mediated by both, noradrenergic and serotonergic
      systems. On the other hand, 21-days administration of VFX significantly decreases
      analgesic action of MRF. Moreover, there is a possibility that VFX acts as an
      antagonist of N-methyl-d-aspartate receptors.

PMID- 25560582
TI  - Association of CYP2C8, CYP2C9 and CYP2J2 gene polymorphisms with myocardial
      infarction in South Indian population.
AB  - BACKGROUND: Cardiovascular diseases (CVDs) are the major cause of mortality and
      morbidity worldwide. Myocardial infarction (MI) is a complex multi-factorial,
      polygenic disorder arising from an interaction between genetic makeup of
      individuals and various environmental factors. CYP2C8, CYP2C9 and CYP2J2 gene
      involved in the metabolism of arachidonic acid, generates epoxyeicosatrienoic
      acids (EETs) that mediate dilation of coronary arteries improving post-ischemic
      cardiac contractile function, reduce vascular inflammation, and increase
      intravascular fibrinolysis. The study is aimed at analyzing the association of
      CYP2C8, CYP2C9 and CYP2J2 gene polymorphisms and MI risk in the South Indian
      population. METHODS: This retrospective study consisted of 287 MI patients, 279
      risk control patients and 321 healthy individuals. Blood samples were collected
      from all the subjects and DNA was isolated using standard phenol-chloroform
      method. Polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) and real time-polymerase chain reaction (RT-PCR) methods were used for
      genotyping. To test the potential independent association between polymorphisms
      and the risk of MI, Multiple-logistic regression analysis was performed. RESULTS:
      Our findings displayed a significant association between CYP2J2*7 (p=0.04;
      OR=2.0) polymorphism and MI while comparing cases with to risk controls. We did
      not observe any association of CYP2C8*2, CYP2C8*3, CYP2C9*2 and CYP2C9*3 with MI.
      CONCLUSION: Our results suggest that individuals with any conventional risk
      factor for MI along with CYP2J2*7 variant allele may be predisposed to risk of MI
      in South Indian population.

PMID- 25560583
TI  - Myelosuppressive and hepatotoxic potential of leflunomide and methotrexate
      combination in a rat model of rheumatoid arthritis.
AB  - BACKGROUND: Safety of the combination of leflunomide and methotrexate was
      examined in several studies with inconclusive results. The present study was
      designed to compare the efficacy and safety of the combination of leflunomide and
      methotrexate in adjuvant-induced arthritis (AIA) in rats focusing on
      immunosuppressive and hepatotoxic effects. METHODS: Eighty four rats were divided
      into seven groups. Group 1: Sham control, group 2: the vehicle control, group 3:
      methotrexate group, group 4-5: leflunomide (5 and 10mg/kg/day) groups, group 6-7:
      combination 1 and 2 [methotrexate+leflunomide (5 and 10mg/kg/day)] groups,
      respectively. RESULTS: The current results indicated that combination therapies
      improved the ankle circumference and clinical scores compared to monotherapies;
      histopathological examination confirmed these findings. The myelosuppressive
      effect of leflunomide (10mg/kg/day) was comparable to that produced by
      methotrexate as indicated by the complete blood count and bone marrow
      cellularity; however their combination resulted in greater toxicity. Furthermore,
      methotrexate greatly affected the splenic histopathology compared to leflunomide
      and the combination therapy produced a greater effect compared to leflunomide not
      methotrexate. Differently, assessment of the hepatotoxic potential of the two
      drugs highlighted that leflunomide induced a dose-dependent increase in the
      fibrosis score which was higher in their magnitude than that induced by
      methotrexate. Leflunomide (10mg/kg/day) and combination 2 groups showed the
      greatest degree of liver fibrosis. CONCLUSIONS: In rats with AIA, current drug
      combinations provided higher therapeutic benefit compared to monotherapies,
      however, greater toxicities were observed. Therefore, continuous monitoring of
      hematologic parameters and liver function will be recommended in clinical
      settings.

PMID- 25560584
TI  - Pinocembrin attenuates hippocampal inflammation, oxidative perturbations and
      apoptosis in a rat model of global cerebral ischemia reperfusion.
AB  - BACKGROUND: Pinocembrin is a major flavonoid molecule isolated from honey and
      propolis. It has versatile pharmacological and biological activities including
      antimicrobial, anti-inflammatory, antioxidant, and anticancer activities as well
      as neuroprotective effects against cerebral ischemic injury. The purpose of the
      current study was to determine the possible mechanisms of neuroprotection
      elicited by pinocembrin with specific emphasis on chronic prophylactic use before
      the induction of global cerebral ischemia reperfusion. METHODS: Global cerebral
      ischemia-reperfusion (I/R) was induced by bilateral carotid artery occlusion for
      15min followed by 60min reperfusion period. Animals were randomly allocated into
      3 groups (n=28): Sham operated, I/R control and rats treated with pinocembrin
      (10mg/kg, po) daily for 7 days then I/R was induced 1h after the last dose of
      pinocembrin. After reperfusion rats were killed by decapitation, brains were
      removed and both hippocampi separated and the following biochemical parameters
      were estimated; lactate dehydrogenase activity, oxidative stress markers (lipid
      peroxides, nitric oxide and reduced glutathione), inflammatory markers
      (myeloperoxidase, tumor necrosis factor-alpha, nuclear factor kappa-B,
      interleukin-6 and interleukin-10), apoptotic biomarkers (caspase 3 and cytochrome
      C), neurotransmitters (glutamate, gamma aminobutyric acid) and infarct size were
      assessed. RESULTS: Pinocembrin ameliorated damage induced by I/R through
      suppressing oxidative stress, inflammatory and apoptotic markers as well as
      mitigating glutamate and lactate dehydrogenase activity. One of the more
      significant findings to emerge from this study is that pinocembrin normalized the
      infarct size elevated by I/R. CONCLUSIONS: Pinocembrin showed a neuroprotective
      effects through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

PMID- 25560585
TI  - Anti-interleukin-1beta antibody prevents the occurrence of repeated restraint
      stress-induced alterations in synaptic transmission and long-term potentiation in
      the rat frontal cortex.
AB  - BACKGROUND: The mechanisms of the influence of prolonged stress on glutamatergic
      transmission and synaptic plasticity in the cerebral cortex remain poorly
      understood. The purpose of this study was to determine an involvement of
      interleukin-1beta (IL-1beta) in the effects of repeated restraint stress on
      excitatory synaptic transmission and long-term potentiation (LTP) in the rat
      frontal cortex. METHODS: The effects of restraint stress lasting for 10 min,
      repeated twice daily for 3 consecutive days were studied ex vivo in the rat
      frontal cortex slices prepared 24h after the last stress session. Rats received
      intraperitoneal injections of interleukin-1beta antibody. In a separate
      experimental group, rats received injections of IL-1beta. Field potentials were
      recorded in the cortical layer II/III. RESULTS: In slices originating from
      stressed animals, the amplitude of field potentials was increased. Consistent
      with the previous studies, restraint stress resulted in a reduced magnitude of
      LTP. Similar effects were evident after administration of IL-1beta. Stress
      induced modifications of the glutamatergic transmission and synaptic plasticity
      were prevented by interleukin-1beta antibody, which was administered 15 min
      before each restraint session. CONCLUSIONS: These data point to an involvement of
      peripherally produced IL-1beta in mediating the influence of repeated restraint
      stress on the functions of the frontal cortex.

PMID- 25560586
TI  - The antinociceptive effect and mechanisms of action of pregabalin in mice.
AB  - BACKGROUND: Pregabalin, a potent anticonvulsant agent, is used in treatment
      resistant epileptic patients. It is reported that pregabalin also has analgesic
      effect in different pain syndromes. However, there is limited data on its
      antinociceptive mechanisms of action. We aimed to investigate the central and
      peripheral antinociceptive effects of pregabalin and the contribution of
      nitrergic, serotonergic, and opioidergic pathways in mice. METHODS: We used tail
      flick, tail clip and hot plate tests to investigate the central antinociceptive
      effects and acetic acid-induced writhing test to assess peripheral
      antinociceptive effects of pregabalin (10, 30, 100mg/kg). We also combined
      pregabalin (100mg/kg) with, a nonspecific nitric oxide synthase inhibitor l-NAME
      (100mg/kg), a serotonin receptor antagonist cyproheptadine (50 MUg/kg), and an
      opioid receptor antagonist naloxone (1mg/kg). RESULTS: Pregabalin 30 mg/kg
      enhanced the percentage of maximal possible effect (% MPE) in tail flick test.
      Pregabalin 100mg/kg significantly increased % MPE in tail clip and tail flick
      tests and decreased the number of writhings. Pregabalin made no significant
      alteration in hot plate test at all doses. The combined use of pregabalin
      100mg/kg with l-NAME, cyproheptadine, and naloxone showed that % MPE was reduced
      only in the combination of pregabalin with naloxone and solely in tail clip test
      while no significant difference was observed in writhing test. CONCLUSIONS: We
      suggest that pregabalin (30 and 100mg/kg) presents central spinal but not central
      supraspinal antinociceptive effect and pregabalin 100mg/kg shows peripheral
      antinociceptive effect. The opioidergic pathway seems to mediate the central
      spinal antinociceptive effect of pregabalin while nitrergic and serotonergic
      pathways are not involved.

PMID- 25560587
TI  - Inhibitory effects of imperatorin on voltage-gated K(+) channels and ATP
      sensitive K(+) channels.
AB  - BACKGROUND: Imperatorin is a furocoumarin isolated from Angelica archangelica and
      Cnidium monnieri. It has multiple neuromodulatory actions such as anticonvulsant
      effects, anxiolytic effects and anti-nociceptive effects. Although there have
      been reports demonstrating its effects on voltage-gated Na(+) channels (VGSC) and
      transient reversal potential (TRP) V1 channels in neurons, there is hitherto no
      work showing whether this compound affects voltage-gated K(+) (Kv) channels and
      ATP-sensitive K(+) (KATP) channels. METHODS: We investigated the effects of
      imperatorin on K(+) channels using whole-cell configuration voltage-clamp
      technique. RESULTS: Imperatorin inhibited Kv channels in differentiated neuronal
      NG108-15 cells, and caused a left shift in the steady-state inactivation curve
      without affecting activation gating. Imperatorin also inhibited heterologously
      expressed wild type Kv1.2 and Kv2.1 channels, but became much less potent in
      inhibiting Kv1.2 V370G, a mutant defective in C-type inactivation, implying that
      drug inhibition depends on C-type inactivation. At a high concentration (100MUM),
      imperatorin also suppressed KATP channels. CONCLUSION: Our results suggest that
      imperatorin inhibited both Kv and KATP channels.

PMID- 25560588
TI  - The effect of carvacrol on systemic inflammation in guinea pigs model of COPD
      induced by cigarette smoke exposure.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a epidemic disease
      which is mainly due to cigarette smoking. The effect of carvacrol on systemic
      inflammation in guinea pig model of COPD was examined in the present study.
      METHODS: Guinea pigs of both sexes were divided into 6 groups, including:
      control, COPD, COPD+drinking water containing three concentrations of carvacrol
      and COPD+dexamethasone. Animals were exposed to cigarette smoke for 3 months in
      order to induce animal model of COPD. Weight changes, serum levels of IL-8 and
      malondialdehyde (MDA) as well as total and differential white blood cell (WBC)
      were measured (n=5 for control and COPD groups and n=6 for other groups).
      RESULTS: Serum levels of IL-8 and MDA, total WBC (p<0.01 for all cases) and
      eosinophil counts (p<0.05) were increased and weight changes were decreased
      (p<0.05) in COPD group compared to controls. Serum MDA level and total WBC in
      treated groups with two higher carvacrol concentrations, eosinophil, neutrophil
      and lymphocyte percentage in those treated with its high concentration as well as
      IL-8 level and weight change in treated groups with its all concentrations and in
      dexamethasone treated group were significantly improved compared to COPD group
      (p<0.05 to p<0.001). CONCLUSION: These results showed a preventive effect of the
      carvacrol on all measured parameter in COPD guinea pigs which was comparable to
      the effect of dexamethasone at used concentrations.

PMID- 25560589
TI  - The effect of central noradrenergic system lesion on dopamine (DA) and serotonin
      (5-HT) synthesis rate following administration of 5-HT3 receptor ligands in
      chosen parts of the rat brain.
AB  - INTRODUCTION: Since little has been known about the effect of the central
      noradrenergic system on the reactivity of serotonin 5-HT3 receptors, the aim of
      the current study was to find out whether this reactivity could be altered by
      chemical damage to the system in adult rats in early developmental stage.
      MATERIALS AND METHODS: Adult male Wistar rats with central noradrenergic lesion
      induced by DSP-4 on day 1 and 3 of life were injected with analgesic model
      substance - morphine, serotoninergic 5-HT3 receptor agonist (1-phenylbiguanide,
      PBG), 5-HT3 receptor antagonist (ondansetron) or both compounds jointly followed
      by decarboxylase inhibitor of aromatic amino acids (NSD-1050). After 30 min
      following NSD-1050 injection, the animals were decapitated using a guillotine.
      Chosen cerebral structures were dissected, and the contents of 5-hydroxytryptofan
      (5-HTP) and l-dihydroxyphenylalanine (l-DOPA) were determined using high-pressure
      liquid chromatography with electrochemical detection (HPLC/ED). RESULTS: Neither
      PBG nor morphine affected l-DOPA contents in the hippocampus in control rats;
      however, DSP-4 lesion caused a significant decrease in the synthesis rate of DA
      in this structure. Hippocampal contents of 5-HTP increased after morphine or PBG
      administration, and central noradrenergic lesion attenuated this effect. Morphine
      or PBG decreased cerebellar DA synthesis rate in control rats and DSP-4 lesion
      did not modify it. Cerebellar levels of 5-HTP increased after morphine or PBG
      challenge in control rats. DSP-4 lesion intensified the effect of morphine and
      attenuated that of PBG. Ondansetron abolished the effects mediated by PBG. We did
      not observe any impact of PBG or ondansetron on DA and 5-HT synthesis in the
      striatum. CONCLUSION: Damage to the central noradrenergic system in rat newborns,
      through altered reactivity of central 5-HT3 receptors, results in permanent
      disorders in serotoninergic transmission in hippocampus and cerebellum as well as
      dopaminergic transmission in hippocampus, which may attenuate the activity of the
      descending pathways that derive from these structures.

PMID- 25560590
TI  - Synergistic antinociceptive interactions between fospropofol and alfentanil in
      mice.
AB  - BACKGROUND: Combination therapy, which provides the opportunity to achieve
      optimal analgesia with reduced side effects at lower drug doses, is a valid
      approach for the treatment of pain. The analgesic interaction between fospropofol
      and alfentanil has not been investigated till date. We sought to determine the
      nature of the interaction between fospropofol and alfentanil in mice models of
      the formalin test, hot-plate test and the tail-flick test. METHODS: The effects
      of fospropofol, alfentanil and their combinations were examined in the formalin
      induced paw inflammatory hyperalgesia, the hot-plate test and the tail-flick test
      in mice. In the three models, dose-response curves were established and their
      respective ED50 (50% effective dose) values were determined separately for each
      agent. Fixed-ratio combinations of fospropofol and alfentanil were tested for
      their combined antinociceptive effects, and the type of interaction was
      determined by the isobolographic analysis. RESULTS: Fospropofol, alfentanil and
      their combination produced a dose-dependent decrease in the number of flinches
      during phase 1 of the formalin test. In the hot-plate test and in the tail-flick
      test, fospropofol, alfentanil and their combination significantly and dose
      dependently prolonged the latency of withdrawal. In the three models,
      isobolographic analysis revealed a significant synergistic interaction between
      fospropofol and alfentanil. The ED50 value for the drug combination was
      significantly lower than the theoretical additive value (p<0.05). CONCLUSIONS:
      The results demonstrate that fospropofol and alfentanil provide synergistic
      antinociceptive interactions in the formalin, hot-plate, and tail-flick tests.
      The observed synergistic interaction between fospropofol and alfentanil are
      indicative of the effectiveness of the combination treatment in pain management
      and should be explored further in patients undergoing minor surgical procedures.

PMID- 25560592
TI  - Lengthening temporalis myoplasty: outcome and radiographic anatomical evaluation
      of length required.

PMID- 25560591
TI  - Antidepressant-like activity of a new piperazine derivative of xanthone in the
      forced swim test in mice: The involvement of serotonergic system.
AB  - BACKGROUND: The studied compound: 3-chloro-5-{[4-(2-hydroxyethyl)piperazin-1
      yl]methyl}-9H-xanthen-9-one dihydrochloride (HBK-6) is a new xanthone derivative.
      In this study we investigated its antidepressant-like properties and possible
      mechanism of action. METHODS: Antidepressant-like activity was evaluated in the
      forced swim test (FST) in mice. The influence on locomotor activity in mice was
      analyzed to determine whether the observed in FST effect is specific. Rotarod
      test was used to determine neurotoxic properties. RESULTS: HBK-6 reduced
      immobility time in mice in FST at the doses 5 and 10mg/kg, whereas fluoxetine
      (FX) at 15 mg/kg, reboxetine (RX) at 10mg/kg and bupropion (BPR) at 5mg/kg. Joint
      administration of sub-effective doses of HBK-6 and FX, but not RX or BPR, reduced
      immobility in mice in FST. HBK-6 at the dose 5mg/kg did not show activity in FST
      after pretreatment with p-chlorophenylalanine. The studied xanthone derivative at
      the doses 5 and 10mg/kg did not impair motor coordination in mice. CONCLUSIONS:
      We demonstrated that HBK-6 has a potent antidepressant-like activity in FST,
      stronger than that of FX and RX, and seems to mediate its effect through
      serotonergic system. Moreover, at antidepressant-like doses it does not show
      neurotoxic properties. Given the promising results, HBK-6 may have potential in
      the treatment of depression, but this needs extended studies.

PMID- 25560593
TI  - Radiological features of non-venomous snakebite hand injury.

PMID- 25560594
TI  - Online support groups for hypospadias.

PMID- 25560595
TI  - Current issues in Barrett's esophagus and Barrett's-related dysplasia.
AB  - Surgical pathologists frequently encounter biopsies in patients with Barrett's
      esophagus (BE), defined as replacement of the normal stratified squamous
      epithelium of the distal esophagus by metaplastic columnar epithelium containing
      goblet cells. Thus, one of the primary roles of the pathologist is to
      definitively identify goblet cells, best done on routine stained sections. It has
      recently been questioned as to whether goblet cells should be absolutely
      necessary to render a diagnosis of BE, given immunohistochemical and flow
      cytometric similarities between columnar-lined esophagus with and without goblet
      cells. Once a diagnosis of BE is rendered, the pathologist must state, using a
      simple classification, whether the biopsy is negative for dysplasia or shows
      dysplasia (low-grade dysplasia or high-grade dysplasia). However, there are a
      number of known pitfalls in distinguishing dysplasia from reactive epithelium,
      and it can be similarly difficult to distinguish low-grade dysplasia from high
      grade dysplasia. In addition, there are some cases in which the distinction of
      high-grade dysplasia from intramucosal adenocarcinoma can be challenging. All of
      these issues are summarized in this paper. 

PMID- 25560596
TI  - Evaluation of colorectal cancers for Lynch syndrome: practical molecular
      diagnostics for surgical pathologists.
AB  - Lynch syndrome is the most common inherited colorectal cancer syndrome,
      accounting for 2-4% of all colorectal cancer cases. This review focuses on the
      tissue workup of Lynch syndrome, including methods to determine whether or not a
      tumor is mismatch repair deficient, and whether a mismatch repair-deficient tumor
      is sporadic or Lynch syndrome-associated. Strategies for determining which tumors
      to test and how best to implement a Lynch syndrome screening program are also
      discussed, as well as potential developments in the future. 

PMID- 25560597
TI  - Duodenal lymphocytosis with no or minimal enteropathy: much ado about nothing?
AB  - Duodenal lymphocytosis is a nonspecific finding that is being detected with
      heightened frequency. Although increased intraepithelial lymphocytosis with
      normal villous architecture classically corresponds to grade 1 of the Marsh
      classification, many other conditions have been reported to be associated with
      this histologic pattern. In this article, we offer a broad review of the
      associations of isolated increased intraepithelial lymphocytosis with celiac and
      nonceliac gluten sensitivity, as well as of the broadening nonceliac etiologies. 

PMID- 25560598
TI  - A contemporary and critical appraisal of 'indeterminate colitis'.
AB  - Distinguishing ulcerative colitis (UC) from Crohn's disease (CD) is normally
      based on evaluation of a variety of clinical, radiologic, serologic and
      pathologic findings, the latter in biopsy and/or resection specimens.
      Unfortunately, some patients with IBD show overlapping pathologic features of UC
      and CD, which makes definite distinction between these two disorders difficult or
      even impossible. In most instances of uncertainty, the patient shows clinical and
      pathologic features of UC, but in addition, the patient's colon resection
      specimen reveals one or more CD-like features. In this setting, a diagnosis of
      indeterminate colitis (IC) is often rendered. IC is not a distinct disease
      entity, and, thus, it has no diagnostic criteria. The most common causes of
      uncertainty in IBD pathology that may lead to a diagnosis of IC in a colon
      resection specimen includes the presence of fulminant (severe and toxic) colitis,
      insufficient radiologic, endoscopic, or pathologic information (including
      analysis of prior biopsies) on the patient, failure to utilize major diagnostic
      criteria as hard evidence in favor of CD, failure to recognize unusual variants
      of UC and CD that may mimic each other, failure to recognize non-IBD mimics and
      other superimposed diseases that cause unusual pathologic features in a resection
      specimen, an attempt to distinguish UC from CD in mucosal biopsies of the colon
      and ileum, or an attempt to change the patients diagnosis (of UC or CD) based on
      pouch or diversion-related complications. Details of each of these causes of
      uncertainty are discussed, in detail, in this review article. A diagnosis of IC
      should never be made clinically or by pathologists based on evaluation of pre
      resection colonic mucosal biopsies. Ultimately, the majority of indeterminate
      cases represent UC, and, thus, most of these patient can be treated safely with a
      colectomy combined with an ileal pouch anal anastomosis procedure. 

PMID- 25560599
TI  - Gastrointestinal tract spindle cell lesions--just like real estate, it's all
      about location.
AB  - Interpretation of gastrointestinal tract mesenchymal lesions is simplified merely
      by knowing in which anatomic layer they are usually found. For example, Kaposi
      sarcoma is detected on mucosal biopsies, whereas inflammatory fibroid polyp is
      nearly always in the submucosa. Gastrointestinal stromal tumors (GISTs) are
      generally centered in the muscularis propria. Schwannomas are essentially always
      in the muscularis propria. Mesenteric lesions are usually found in the small
      bowel mesentery. Knowledge of the favored layer is even most important in
      interpreting colon biopsies, as many mesenschymal polyps are encountered in the
      colon. Although GISTs are among the most common mesenchymal lesions, we will
      concentrate our discussion on other mesenchymal lesions, some of which are in the
      differential diagnosis of GIST, and point out some diagnostic pitfalls,
      particularly in immunolabeling. 

PMID- 25560600
TI  - Mucinous epithelial neoplasms of the appendix and pseudomyxoma peritonei.
AB  - The classification of appendiceal mucinous neoplasms has been controversial,
      largely focused on a particular subset of low-grade mucinous tumors that, despite
      their innocuous appearance, can disseminate to the peritoneal cavity as
      pseudomyxoma peritonei (PMP). Recent WHO classification of these tumors as low
      grade appendiceal mucinous neoplasms acknowledges their unique morphologic
      appearance and biologic behavior. Still, debate about the use of this term and
      its parameters continues to impede the adoption of consensus classification for
      appendiceal mucinous neoplasms. The classification of PMP has also been the
      subject of debate, with international authorities advocating for the use of
      malignant terminology to describe all grades of PMP, even though some authorities
      consider low-grade PMP to be dissemination of adenomatous epithelium in the
      peritoneum. Recent data also emphasize the importance of histologic grade of the
      peritoneal tumors in defining prognosis of these patients. 

PMID- 25560602
TI  - The pathology of serrated colorectal neoplasia: practical answers for common
      questions.
AB  - In the past 10-15 years, recognition and considerable understanding of much of
      the so-called 'serrated pathway' of colorectal neoplasia has emerged, although
      much remains to be discovered. Key elements appear to be a propensity for the
      elderly, females more than males, and right colon; precursor lesions with
      serrations; and frequent BRAF mutations, hypermethylation (particularly involving
      the MHL1 promoter), and resultant dysfunctional DNA mismatch repair and
      microsatellite instability (MSI) of the colorectal adenocarcinomas. For the
      anatomic pathologist, this has created challenges in sometimes having to
      morphologically subdivide once-comfortable hyperplastic polyps into hyperplastic
      polyps and 'sessile serrated adenoma/polyps' (SSA/Ps), learn to distinguish these
      from 'traditional' serrated adenomas, and learn to recognize biologically
      progressing forms of SSA/Ps known as 'sessile serrated adenoma with cytological
      dysplasia'. The goal of this article is to highlight for the practicing anatomic
      pathologist the current status of our understanding of serrated colorectal
      neoplasms from a practical perspective. 

PMID- 25560601
TI  - Eosinophils in the GI tract: how many is too many and what do they mean?
AB  - Eosinophils are commonly detected in normal mucosal biopsies from all sites
      within the gastrointestinal tract where they are dispersed in the lamina propria
      and, to a lesser extent, in the epithelium. The distinction between the upper
      limit of normal and abnormally increased tissue eosinophils is not well defined.
      However, eosinophils that infiltrate the epithelium in more than occasional
      numbers, coalesce to form aggregates, or show extensive degranulation are always
      abnormal and raise a broad differential diagnosis. Although the differential
      diagnosis of purely eosinophilic inflammation is largely limited to
      hypersensitivity reactions and some infections, they are increased in several
      gastrointestinal conditions, including gastroesophageal reflux disease,
      autoimmune gastritis, infections, drug reactions, inflammatory bowel disease,
      radiation enteritis, and collagen vascular disease. These disorders feature
      eosinophils as one component of a mixed inflammatory infiltrate that can, in some
      instances, be prominent enough to cause diagnostic confusion. The purpose of this
      review is to discuss the normal distribution of eosinophils in the
      gastrointestinal tract and the differential diagnosis of inflammatory conditions
      that feature prominent eosinophilia. 

PMID- 25560603
TI  - Bowel cancer screening-generated diagnostic conundrum of the century:
      pseudoinvasion in sigmoid colonic polyps.
AB  - The introduction of bowel cancer screening, in the United Kingdom, United States
      of America, and many other Western countries, has provided considerable interest
      and no little diagnostic consternation for pathologists. In the United Kingdom,
      the universal introduction of bowel cancer screening, initially by fecal occult
      blood testing and more recently by the introduction of flexible sigmoidoscopy,
      has provided four main areas of pathological diagnostic difficulty. This is the
      biopsy diagnosis of adenocarcinoma, serrated pathology, the diagnosis and
      management of polyp cancer, and, finally, the phenomenon of
      pseudoinvasion/epithelial misplacement (PEM), particularly in sigmoid colonic
      adenomatous polyps. The diagnostic difficulties associated with the latter
      phenomenon have provided particular problems that have led to the institution of
      a UK national 'Expert Board', comprising three pathologists, who adjudicate on
      difficult cases. The pathological features favoring PEM are well recognized but
      there is no doubt that there can be profound mimicry of adenocarcinoma, and, as
      yet, no adjunctive diagnostic tools have been developed to allow the
      differentiation in difficult cases. Research in this area is proceeding and some
      methodologies do show promise in this difficult diagnostic area. 

PMID- 25560604
TI  - Serosal surfaces, mucin pools, and deposits, oh my: challenges in staging
      colorectal carcinoma.
AB  - Colorectal carcinoma is the third most common cancer in the United States. Proper
      and standardized pathologic staging is vital for prognostic assessment and
      impacts therapeutic decisions. The Tumor Node Metastasis (TNM) staging system was
      developed by the American Joint Committee on Cancer (AJCC) to be a data-driven,
      evidence-based staging system providing an accurate prediction of outcome. The
      AJCC 7th edition (2010) included several changes clarifying some issues and
      leading to new controversies. We aim to address selected challenging issues in
      tumor T staging, neoadjuvant treatment effects in rectal cancer, and definition
      of lymph node vs tumor deposit. Serosal involvement in colorectal cancer is
      staged as T4, which is associated with decreased survival and may impact
      additional therapy decisions. Although careful sampling and sectioning are
      helpful, challenges remain in interpretation of tumor within 1 mm of serosal
      surface with a reaction. Elastic stain as a surrogate marker for serosal invasion
      has been studied, but its usefulness remains unclear. Some unique issues in
      rectal cancer include the presence of serosa in proximal but not in distal tumors
      and post-neoadjuvant effects. Tumor should be staged based on tumor cells rather
      than acellular mucin pools. Additionally, tumor response should be graded only in
      primary tumor but not in lymph nodes or metastatic sites. The distinction between
      tumor deposits and lymph nodes has been modified in AJCC TNM from using size in
      the 5th edition, to the round contour in the 6th edition, to only features of
      residual lymph node architecture in the 7th edition. Interobserver variability
      remains but tumor deposits should be documented when present. The number of
      deposits should not be added to the total number of positive lymph nodes, and the
      N1c designation should only be used in cases without any positive lymph nodes.
      Future clarification will likely evolve as more data become available. 

PMID- 25560606
TI  - The role of the Gulf Stream in European climate.
AB  - The Gulf Stream carries the warm, poleward return flow of the wind-driven North
      Atlantic subtropical gyre and the Atlantic Meridional Overturning Circulation.
      This northward flow drives a significant meridional heat transport. Various lines
      of evidence suggest that Gulf Stream heat transport profoundly influences the
      climate of the entire Northern Hemisphere and, thus, Europe's climate on
      timescales of decades and longer. The Gulf Stream's influence is mediated through
      feedback processes between the ocean, atmosphere, and cryosphere. This review
      synthesizes paleoclimate archives, model simulations, and the instrumental
      record, which collectively suggest that decadal and longer-scale variability of
      the Gulf Stream's heat transport manifests in changes in European temperature,
      precipitation, and storminess. Given that anthropogenic climate change is
      projected to weaken the Atlantic Meridional Overturning Circulation, associated
      changes in European climate are expected. However, large uncertainty in the
      magnitude of the anticipated weakening undermines the predictability of the
      future climate in Europe. 

PMID- 25560607
TI  - Denitrification, anammox, and N2 production in marine sediments.
AB  - Fixed nitrogen limits primary productivity in many parts of the global ocean, and
      it consequently plays a role in controlling the carbon dioxide content of the
      atmosphere. The concentration of fixed nitrogen is determined by the balance
      between two processes: the fixation of nitrogen gas into organic forms by
      diazotrophs, and the reconversion of fixed nitrogen to nitrogen gas by
      denitrifying organisms. However, current sedimentary denitrification rates are
      poorly constrained, especially in permeable sediments, which cover the majority
      of the continental margin. Also, anammox has recently been shown to be an
      additional pathway for the loss of fixed nitrogen in sediments. This article
      briefly reviews sedimentary fixed nitrogen loss by sedimentary denitrification
      and anammox, including in sediments in contact with oxygen-deficient zones. A
      simple extrapolation of existing rate measurements to the global sedimentary
      denitrification rate yields a value smaller than many existing measurement-based
      estimates but still larger than the rate of water column denitrification. 

PMID- 25560605
TI  - microRNAs function in CD8+T cell biology.
AB  - During an immune response, CD8(+)T cells can differentiate into multiple types of
      effector and memory cells that are important components of immune surveillance.
      However, their dysregulation has been implicated in infection with viruses or
      intracellular bacteria and tumorigenesis. miRNAs have been identified as crucial
      regulators of gene expression, and they perform this function by repressing
      specific target genes at the post-transcriptional level. Most miRNAs expressed in
      a given cell type serve the function to impede broadly cell-type-inappropriate
      gene expression and potently deepen a pre-existing differentiation program. It is
      increasingly recognized that miRNAs directly modulate the concentration of many
      regulatory proteins that are required for the development of immune cells in the
      thymus and their responses in the periphery. This review outlines our current
      understanding of the function of miRNAs in CD8(+)T cell biology as it impacts
      expression of protein-coding genes in the context of proper development,
      infection, as well as oncogenesis. In addition, we conclude with a perspective on
      future challenges and the clinical relevance of miRNA biology. 

PMID- 25560608
TI  - The determination of normal percentages of syncytiotrophoblastic knots in various
      regions of placenta: where to count the syncytial knots.
AB  - OBJECTIVE: The marginal, basal and subchorial regions of the placenta are
      considered to be more hypoxic than other regions. Therefore, it is not
      recommended to determine the increase in syncytiotrophoblast knots, based on the
      major morphological change in placental hypoxia, from the samples taken from
      these regions. However, the normal count of knots at various regions of placenta
      is not investigated. MATERIAL AND METHOD: In this study we have sampled
      morphologically and clinically normal placenta with eccentric cord insertion from
      various sites, either close to cord entrance or away from it (marginal, non
      marginal basal, non-marginal subchorial, and nonmarginal midparanchymal). The
      number of knots was calculated on a total of at least 100 villi for each
      placental sample. The normal amount of knots in different regions and comparison
      between them were investigated. Twenty-eight placentas with eccentric cord
      insertion were sampled in the same manner. Hot spots from the above mentioned
      regions were counted in a total of 100 villi. RESULTS: No significant difference
      was found between the dual comparison of the mean percentages of different
      regions (p: 0.148). The variety of hypoxia in different regions of the placenta
      could not be demonstrated in this study. CONCLUSION: It is found that there is no
      difference in perfusion that can be morphologically demonstrated with increase in
      syncytiotrophoblast knot, between different regions of placenta.

PMID- 25560609
TI  - Diagnostic power and pitfalls of intraoperative consultation (frozen section) in
      rhabdomyosarcoma.
AB  - OBJECTIVE: Intraoperative consultation plays an important role in the management
      of soft tissue sarcomas, such as rhabdomyosarcoma. In this study, we aimed to
      draw attention to the important points during frozen section interpretation, and
      analyse the accuracy of frozen diagnosis in rhabdomyosarcoma patients. MATERIAL
      AND METHOD: The cases, both diagnosed as rhabdomyosarcoma or followed with a
      history of rhabdomyosarcoma, and interpreted with intraoperative consultation
      (frozen section) between 2000 and 2013 were culled from pathology archives. The
      diagnoses were confirmed by desmin and myogenin, immunohistochemically. The
      frozen and final diagnoses were noted of 21 biopsy specimens of 19 patients.
      Sensitivity and specificity of intraoperative consultation were calculated
      regarding to the major diagnostic discrepancies leading to a change in surgical
      management of the patient, after exclusion of the cases deferred to paraffin
      section. RESULTS: Of the evaluated 21 biopsy material, 3 (14%) were misdiagnosed:
      Of the 2 false negative embryonal rhabdomyosarcoma cases, sample was not
      representative of the tumor, and there was chemo/radiotherapy induced changes in
      the other case. In the only false positively diagnosed case with a known history
      of rhabdomyosarcoma, inflammatory cells were misinterpreted as small round cell
      neoplasm. In 5 (29%) of 21 biopsies, a frozen diagnosis could not be given, and
      the diagnosis was deferred. Six cases (29%) were evaluated with cytological
      squash or imprint preparation; none of the misdiagnosed cases was evaluated with
      adjunct cytological preparation. Six of 8 misdiagnosed or deferred biopsies
      showed morphological changes secondary to radiotherapy and/or chemotherapy.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value were calculated as 85%, 67%, 92% and 50%, respectively. CONCLUSION:
      Intraoperative consultation for rhabdomyosarcoma is a reliable tool with high
      sensitivity and fair specificity. Cases with treatment effect may lead to
      diagnostic difficulties, especially false negative results. Understanding the
      diagnostic algorithm of surgeon may prevent misdiagnosis of frozen specimen. Our
      results also emphasize the diagnostic role of intraoperative cytology as an
      adjunct to frozen section.

PMID- 25560610
TI  - Clinico-pathological study to evaluate oral lichen planus for the establishment
      of clinical and histopathological diagnostic criteria.
AB  - OBJECTIVE: Lichen planus and lichenoid lesions affecting the oral cavity show
      similar clinico-pathological features creating a diagnostic dilemma. Hence, the
      aim of the present study was to establish a clinical and histopathological
      correlation in the diagnosis of oral lichen planus, based on the modified WHO
      diagnostic criteria of oral lichen planus and oral lichenoid lesions proposed by
      Van der Meij and Van der Waal in 2003. MATERIAL AND METHOD: In the present study,
      100 cases of oral lichen planus were clinically and histopathologically analyzed.
      Out of the 100 cases, 50 were prospective and 50 were retrospective cases.
      Prospective cases were collected based on the clinical diagnosis of oral lichen
      planus and oral lichenoid lesion. Retrospective cases were collected based on the
      histopathological diagnosis of oral lichen planus. Both the clinical and
      histopathological analyses were performed based on a proposal for a set of
      modified diagnostic criteria of oral lichen planus and oral lichenoid lesion. A
      final diagnosis of oral lichen planus was made only after the correlation of the
      clinical diagnosis with the histopathological diagnosis. RESULTS: The
      interobserver agreement among three observers for both prospective and
      retrospective cases in the final diagnosis of oral lichen planus was found to be
      "good" to "very good" indicating high reproducibility. However, the final
      diagnoses of true oral lichen planus after clinico-pathological correlation in
      prospective and retrospective study groups appeared to be 38.0% and 54.0%
      respectively. CONCLUSION: The results of the present study revealed mild to
      moderate clinico-pathological correlation in the final diagnosis of oral lichen
      planus for the prospective and retrospective study groups respectively.

PMID- 25560611
TI  - Pleuropulmonary blastoma: a case report.
AB  - Pleuropulmonary blastoma is rare embryonal tumor of infancy and early childhood
      and it often arises from lung and more rarely from the parietal pleura. We
      present this entity which has no systematic data associated with its incidence in
      order to discuss clinical, histopathological, immunohistochemical features and
      the differential diagnosis. A three-year-old boy presented with fever showed
      signs of upper respiratory tract infection. Radiological examination revealed a
      solid mass filling the right hemithorax. The patient underwent core needle
      biopsy, wedge biopsy and lobectomy. Biopsy and surgical material were examined
      histopathologically. The tumor was composed of predominantly solid areas
      consisting blastemal cells with spindle, polygonal and round nuclei in the myxoid
      stroma. Immunohistochemical staining of the tumor cells were positive with
      vimentin and desmin. MIB-1 labeling index was above 90%. Histological diagnosis
      was pleuropulmonary blastoma type 3. The surgically sampled adjacent diafragma
      was also infiltrated with the tumor. The patient was treated with chemotherapy
      and showed no signs of recurrence in the follow-up of 9 months. Pleuropulmonary
      blastoma is a very rare childhood cancer that needs to be kept in mind in the
      pathological differential diagnosis of thoracic tumors in the children. 

PMID- 25560612
TI  - CAMTA1 immunostaining is not useful in differentiating epithelioid
      hemangioendothelioma from its potential mimickers.

PMID- 25560613
TI  - Effects of vitamin E blending on plastic deformation mechanisms of highly
      crosslinked ultrahigh molecular weight polyethylene (HXL-UHMWPE) in total hip
      arthroplasty.
AB  - The molecular mobility and crystalline texture development in highly crosslinked
      ultrahigh molecular weight polyethylene (HXL-UHMWPE) blended with antioxidant
      vitamin E (VE, dl-alpha-tocopherol) were studied via uniaxial compression at room
      temperature by means of confocal/polarized Raman spectroscopy. The results were
      compared to morphological analyses under the same compression conditions
      performed on HXL-UHMWPE prepared in exactly the same way but blending VE into the
      polyethylene resin (VE-free HXL-UHMWPE). These comparative analyses allow us to
      evaluate the physical role of VE in morphological alterations of HXL-UHMWPE
      induced by compression deformation, which can greatly affect its micromechanical
      behavior. Molecular rearrangement and phase transitions in crystalline and non
      crystalline phase, i.e. amorphous and intermediate (third) phase, were found to
      be part of a reconstruction process after plastic deformation in the samples.
      Although VE-blended HXL-UHMWPE exhibited more pronounced molecular mobility, as
      evidenced by its significant deformation-induced texturing, crystallinity change
      was totally inhibited by the presence of VE during deformation. On the other
      hand, amorphous-to-intermediate phase transition was confirmed. VE-free HXL
      UHMWPE also presented significant crystallization after deformation, but its
      surface texture evolution occurred to a much lesser extent. This study suggests
      that the addition of VE induced earlier activation of compression deformation
      modes in crystalline and non-crystalline phases (e.g. chain slip, interlamellar
      shear and rotation) due to an increase in polyethylene chain mobility. 

PMID- 25560614
TI  - Fabrication of novel Si-doped hydroxyapatite/gelatine scaffolds by rapid
      prototyping for drug delivery and bone regeneration.
AB  - Porous 3-D scaffolds consisting of gelatine and Si-doped hydroxyapatite were
      fabricated at room temperature by rapid prototyping. Microscopic characterization
      revealed a highly homogeneous structure, showing the pre-designed porosity
      (macroporosity) and a lesser in-rod porosity (microporosity). The mechanical
      properties of such scaffolds are close to those of trabecular bone of the same
      density. The biological behavior of these hybrid scaffolds is greater than that
      of pure ceramic scaffolds without gelatine, increasing pre-osteoblastic MC3T3-E1
      cell differentiation (matrix mineralization and gene expression). Since the
      fabrication process of these structures was carried out at mild conditions, an
      antibiotic (vancomycin) was incorporated in the slurry before the extrusion of
      the structures. The release profile of this antibiotic was measured in phosphate
      buffered saline solution by high-performance liquid chromatography and was
      adjusted to a first-order release kinetics. Vancomycin released from the material
      was also shown to inhibit bacterial growth in vitro. The implications of these
      results for bone tissue engineering applications are discussed. 

PMID- 25560616
TI  - Message from the International Federation of Cell Biology.

PMID- 25560617
TI  - A message from the Editor.

PMID- 25560615
TI  - The BBA33 lipoprotein binds collagen and impacts Borrelia burgdorferi
      pathogenesis.
AB  - Borrelia burgdorferi, the etiologic agent of Lyme disease, adapts to the
      mammalian hosts by differentially expressing several genes in the BosR and Rrp2
      RpoN-RpoS dependent pathways, resulting in a distinct protein profile relative to
      that seen for survival in the Ixodes spp. tick. Previous studies indicate that a
      putative lipoprotein, BBA33, is produced in an RpoS-dependent manner under
      conditions that mimic the mammalian component of the borrelial lifecycle.
      However, the significance and function for BBA33 is not known. Given its linkage
      to the BosR/Rrp2-RpoN-RpoS regulatory cascade, we hypothesized that BBA33
      facilitates B. burgdorferi infection in the mammalian host. The deletion of bba33
      eliminated B. burgdorferi infectivity in C3H mice, which was rescued by genetic
      complementation with intact bba33. With regard to function, a combinatorial
      peptide approach, coupled with subsequent in vitro binding assays, indicated that
      BBA33 binds to collagen type VI and, to a lesser extent, collagen type IV. Whole
      cell binding assays demonstrated BBA33-dependent binding to human collagen type
      VI. Taken together, these results suggest that BBA33 interacts with collagenous
      structures and may function as an adhesin in a process that is required to
      prevent bacterial clearance. 

PMID- 25560618
TI  - Ethanol extract of Dalbergia odorifera protects skin keratinocytes against
      ultraviolet B-induced photoaging by suppressing production of reactive oxygen
      species.
AB  - Dalbergia odorifera T. Chen (Leguminosae), an indigenous medicinal herb, has been
      widely used in northern and eastern Asia to treat diverse diseases. Here, we
      investigated the anti-senescent effects of ethanolic extracts of Dalbergia
      odorifera (EEDO) in ultraviolet (UV) B-irradiated skin cells. EEDO significantly
      inhibited UVB-induced senescence of human keratinocytes in a concentration
      dependent manner, concomitant with inhibition of reactive oxygen species (ROS)
      generation. UVB-induced increases in the levels of p53 and p21, biomarkers of
      cellular senescence, were almost completely abolished in the presence of EEDO.
      Sativanone, a major constituent of EEDO, also attenuated UVB-induced senescence
      and ROS generation in keratinocytes, indicating that sativanone is an indexing
      (marker) molecule for the anti-senescence properties of EEDO. Finally, treatment
      of EEDO to mice exposed to UVB significantly reduced ROS levels and the number of
      senescent cells in the skin. Thus, EEDO confers resistance to UVB-induced
      cellular senescence by inhibiting ROS generation in skin cells. 

PMID- 25560619
TI  - Incomplete Lemierre syndrome.
AB  - An invasive Fusobacterium infection may originate from an apparent routine
      pharyngitis and lead to significant distant septic complications. Even without
      internal jugular thrombosis, the same mechanism of disease exists, and therefore,
      the same morbidity, prognosis, and treatments are applicable, hence the suitable
      term incomplete Lemierre syndrome. We present a case of invasive Fusobacterium
      infection that meets all criteria for Lemierre syndrome except lacking internal
      jugular thrombosis. A review of the literature that forms the diagnostic criteria
      for this syndrome and the rationale for our creating this novel term is
      presented. 

PMID- 25560620
TI  - Hip pain and fever: when it's not a septic joint, what's next?
AB  - Hip pain and fever in children include a broad differential. Most concerning is
      the possible diagnosis of a septic joint, which carries significant morbidity. We
      describe the case of a 13-year-old boy with fever and hip pain who was referred
      to the emergency department with concern for septic hip. The etiology was later
      discovered to be pyomyositis from methicillin-resistant Staphylococcus aureus. In
      areas with high prevalence of community-acquired methicillin-resistant
      Staphylococcus aureus, it is important for physicians to be aware of this rare,
      but potentially complicated condition. 

PMID- 25560621
TI  - Late presenting Bochdalek hernia with gastric perforation.
AB  - Late-onset congenital diaphragmatic hernias that give symptoms beyond the
      neonatal period are rare and are difficult to diagnose. The diagnosis is usually
      made in case of complications such as intestinal obstruction, strangulation, and
      perforation, which further necessitate immediate surgical repair. The case of a 5
      year-old child presenting with acute respiratory distress with gastric
      strangulation and perforation secondary to Bochdalek hernia is reported here.
      Although presentation in the latter ages is less common, congenital diaphragmatic
      hernia should be included in the differential diagnosis of respiratory distress
      in children. Symptoms and diagnostic tools should truly be interpreted.
      Gastrointestinal complications must urgently be recognized, and early surgical
      intervention must be performed. 

PMID- 25560622
TI  - The role of ultrasound in the emergency department evaluation of the acutely
      painful pediatric hip.
AB  - Children presenting with hip pain or a limp are a diagnostic challenge for the
      clinician. The differential diagnosis is extensive, and the workup can be broad.
      This review focuses on differentiating between transient synovitis and septic
      arthritis of the hip. The role of bedside ultrasound in the clinical evaluation
      of these patients is addressed, including the technique and appropriate
      indications for bedside ultrasound of the hip in the emergency department. 

PMID- 25560624
TI  - Identification of a pediatric intra-abdominal cystic lymphangioma using point-of
      care ultrasonography.
AB  - Intra-abdominal cystic lymphangiomas are rare, benign congenital tumors that
      often present with vague symptoms, making diagnosis difficult. We report a case
      of a 4-year-old patient who presented to the emergency department with
      nonspecific abdominal pain. Her diagnosis of intra-abdominal cystic lymphangioma
      was facilitated by point-of-care ultrasonography. 

PMID- 25560625
TI  - Preparing for International Classification of Diseases, 10th Revision, Clinical
      Modification implementation: strategies for maintaining an efficient workflow.
AB  - The International Classification of Diseases, 10th Revision, is required to be
      used by the Centers for Medicare and Medicaid Services health care billing data
      starting in October 2015 in the United States. The International Classification
      of Diseases, 10th Revision, is an update to the International Classification of
      Diseases, Ninth Revision, and contains approximately 70,000 codes compared with
      14,000 codes. We aimed to discuss how our institution is updating the coding
      system in a manner that alleviates the possible burden placed on providers
      including more coding information required and longer load times. We performed a
      simulation test including testing the diagnosis calculator, timing, and how well
      the new and old codes mapped. We conducted a gap analysis to ensure that coding
      could begin in October of 2015 with minimal service interruptions. We will
      describe strategies and procedures to transition between systems while
      maintaining efficiency and helping to improve classification. 

PMID- 25560626
TI  - The Pediatric Emergency Care Applied Research Network: a history of multicenter
      collaboration in the United States.
AB  - In this article, we review the history and progress of a large multicenter
      research network pertaining to emergency medical services for children. We
      describe the history, organization, infrastructure, and research agenda of the
      Pediatric Emergency Care Applied Research Network and highlight some of the
      important accomplishments since its inception. We also describe the network's
      strategy to grow its research portfolio, train new investigators, and study how
      to translate new evidence into practice. This strategy ensures not only the
      sustainability of the network in the future but the growth of research in
      emergency medical services for children in general. 

PMID- 25560627
TI  - Pediatric emergency medicine: legal briefs.

PMID- 25560628
TI  - ECGs in the ED.

PMID- 25560629
TI  - Cognitive motor interference for gait and balance in stroke: a systematic review
      and meta-analysis.
AB  - BACKGROUND AND PURPOSE: An increasing interest in the potential benefits of
      cognitive motor interference (CMI) for stroke has recently been observed, but the
      efficacy of CMI for gait and balance is controversial. A systematic review and
      meta-analysis of randomized controlled trials was performed to estimate the
      effect of CMI on gait and balance in patients with stroke. METHODS: Articles in
      Medline, EMBASE, the Cochrane Library, Web of Science, CINAHL, PEDro and the
      China Biology Medicine disc were searched from 1970 to July 2014. Only randomized
      controlled trials examining the effects of CMI for patients with stroke were
      included, and no language restrictions were applied. Main outcome measures
      included gait and balance function. RESULTS: A total of 15 studies composed of
      395 participants met the inclusion criteria, and 13 studies of 363 participants
      were used as data sources for the meta-analysis. Pooling revealed that CMI was
      superior to the control group for gait speed [mean difference (MD) 0.19 m/s, 95%
      confidence interval (CI) (0.06, 0.31), P = 0.003], stride length [MD 12.53 cm,
      95% CI (4.07, 20.99), P = 0.004], cadence [MD 10.44 steps/min, 95% CI (4.17,
      16.71), P = 0.001], centre of pressure sway area [MD -1.05, 95% CI (-1.85, 
      0.26), P = 0.01] and Berg balance scale [MD 2.87, 95% CI (0.54, 5.21), P = 0.02]
      in the short term. CONCLUSION: Cognitive motor interference is effective for
      improving gait and balance function for stroke in the short term. However, only
      little evidence supports assumptions regarding CMI's long-term benefits.

PMID- 25560631
TI  - Benchmarking database performance for genomic data.
AB  - Genomic regions represent features such as gene annotations, transcription factor
      binding sites and epigenetic modifications. Performing various genomic operations
      such as identifying overlapping/non-overlapping regions or nearest gene
      annotations are common research needs. The data can be saved in a database system
      for easy management, however, there is no comprehensive database built-in
      algorithm at present to identify overlapping regions. Therefore I have developed
      a novel region-mapping (RegMap) SQL-based algorithm to perform genomic operations
      and have benchmarked the performance of different databases. Benchmarking
      identified that PostgreSQL extracts overlapping regions much faster than MySQL.
      Insertion and data uploads in PostgreSQL were also better, although general
      searching capability of both databases was almost equivalent. In addition, using
      the algorithm pair-wise, overlaps of >1000 datasets of transcription factor
      binding sites and histone marks, collected from previous publications, were
      reported and it was found that HNF4G significantly co-locates with cohesin
      subunit STAG1 (SA1).Inc.

PMID- 25560630
TI  - Modified molecular interactions of the pheophytin and plastoquinone electron
      acceptors in photosystem II of chlorophyll D-containing Acaryochloris marina as
      revealed by FTIR spectroscopy.
AB  - Acaryochloris marina is a unique cyanobacterium that contains chlorophyll (Chl) d
      as a major pigment. Because Chl d has smaller excitation energy than Chl a used
      in ordinary photosynthetic organisms, the energetics of the photosystems of A.
      marina have been the subject of interest. It was previously shown that the redox
      potentials (E m's) of the redox-active pheophytin a (Pheo) and the primary
      plastoquinone electron acceptor (QA) in photosystem II (PSII) of A. marina are
      higher than those in Chl a-containing PSII, to compensate for the smaller
      excitation energy of Chl d (Allakhverdiev et al., Proc Natl Acad Sci USA 107:
      3924-3929, 2010; ibid. 108: 8054-8058, 2011). To clarify the mechanisms of these
      E m increases, in this study, we have investigated the molecular interactions of
      Pheo and QA in PSII core complexes from A. marina using Fourier transform
      infrared (FTIR) spectroscopy. Light-induced FTIR difference spectra upon single
      reduction of Pheo and QA showed that spectral features in the regions of the keto
      and ester C=O stretches and the chlorin ring vibrations of Pheo and in the CO/CC
      stretching region of the Q A (-) semiquinone anion in A. marina are significantly
      different from those of the corresponding spectra in Chl a-containing
      cyanobacteria. These observations indicate that the molecular interactions,
      including the hydrogen bond interactions at the C=O groups, of these cofactors
      are modified in their binding sites of PSII proteins. From these results, along
      with the sequence information of the D1 and D2 proteins, it is suggested that A.
      marina tunes the E m's of Pheo and QA by altering nearby hydrogen bond networks
      to modify the structures of the binding pockets of these cofactors. 

PMID- 25560633
TI  - Potentials of mean force and escape times of surfactants from micelles and
      hydrophobic surfaces using molecular dynamics simulations.
AB  - We calculate potentials of mean force (PMFs) and mean first passage times for a
      surfactant to escape a micelle, for both ionic sodium dodecyl sulfate (SDS) and
      nonionic ethoxylated alcohol (C12E5) micelles using both atomistic and coarse
      grained molecular dynamics (MD) simulations. The PMFs are obtained by umbrella
      sampling and used in a Smoluchowski first-passage-time theory to obtain the times
      for a surfactant to escape a micelle. The calculated mean first passage time for
      an SDS molecule to break away from a micelle (with an aggregation number of 60)
      is around 2 MUs, which is consistent with previous experimental measurements of
      the "fast relaxation time" for exchange of surfactants between the micellar phase
      and the bulk solvent. The corresponding escape time calculated for a nonionic
      ethoxylated alcohol C12E5, with the same tail length as SDS, is 60 MUs, which is
      significantly longer than for SDS primarily because the PMF for surfactant
      desorption is about 3kT smaller than for C12E5. We also show that two coarse
      grained (CG) force fields, MARTINI and SDK, give predictions similar to the
      atomistic CHARMM force field for the nonionic C12E5 surfactant, but for the ionic
      SDS surfactant, the CG simulations give a PMF similar to that obtained with
      CHARMM only if long-range electrostatic interactions are included in the CG
      simulations, rather than using a shifted truncated electrostatic interaction. We
      also calculate that the mean first passage time for an SDS and a C12E5 to escape
      from a latex binder surface is of the order of milliseconds, which is more than
      100 times longer than the time for escape from the micelle, indicating that in
      latex waterborne coatings, SDS and C12E5 surfactants likely bind preferentially
      to the latex polymer interface rather than form micelles, at least at low
      surfactant concentrations. 

PMID- 25560632
TI  - Melanoma cells influence the differentiation pattern of human epidermal
      keratinocytes.
AB  - BACKGROUND: Nodular melanoma is one of the most life threatening tumors with
      still poor therapeutic outcome. Similarly to other tumors, permissive
      microenvironment is essential for melanoma progression. Features of this
      microenvironment are arising from molecular crosstalk between the melanoma cells
      (MC) and the surrounding cell populations in the context of skin tissue. Here, we
      study the effect of melanoma cells on human primary keratinocytes (HPK). Presence
      of MC is as an important modulator of the tumor microenvironment and we compare
      it to the effect of nonmalignant lowly differentiated cells also originating from
      neural crest (NCSC). METHODS: Comparative morphometrical and immunohistochemical
      analysis of epidermis surrounding nodular melanoma (n = 100) was performed. Data
      were compared to results of transcriptome profiling of in vitro models, in which
      HPK were co-cultured with MC, normal human melanocytes, and NCSC, respectively.
      Differentially expressed candidate genes were verified by RT-qPCR. Biological
      activity of candidate proteins was assessed on cultured HPK. RESULTS: Epidermis
      surrounding nodular melanoma exhibits hyperplastic features in 90% of cases. This
      hyperplastic region exhibits aberrant suprabasal expression of keratin 14
      accompanied by loss of keratin 10. We observe that MC and NCSC are able to
      increase expression of keratins 8, 14, 19, and vimentin in the co-cultured HPK.
      This in vitro finding partially correlates with pseudoepitheliomatous hyperplasia
      observed in melanoma biopsies. We provide evidence of FGF-2, CXCL-1, IL-8, and
      VEGF-A participation in the activity of melanoma cells on keratinocytes.
      CONCLUSION: We conclude that the MC are able to influence locally the
      differentiation pattern of keratinocytes in vivo as well as in vitro. This
      interaction further highlights the role of intercellular interactions in
      melanoma. The reciprocal role of activated keratinocytes on biology of melanoma
      cells shall be verified in the future.

PMID- 25560634
TI  - Observation of excitonic fine structure in a 2D transition-metal dichalcogenide
      semiconductor.
AB  - Two-dimensional (2D) semiconductors, such as transition-metal dichalcogenide
      monolayers (TMD 1Ls), have attracted increasing attention owing to the underlying
      fundamental physics (e.g., many body effects) and the promising optoelectronic
      applications such as light-emitting diodes. Though much progress has been made,
      intrinsic excitonic states of TMD 1Ls are still highly debated in theory, which
      thirsts for direct experimental determination. Here, we report unconventional
      emission and excitonic fine structure in 1L WS2 revealed by electrical doping and
      photoexcitation, which reflects the interplay of exciton, trion, and other
      excitonic states. Tunable excitonic emission has been realized in a controllable
      manner via electrical and/or optical injection of charge carriers. Remarkably
      enough, the superlinear (i.e., quadratic) emission is unambiguously observed
      which is attributed to biexciton states, indicating the strong Coulomb
      interactions in such a 2D material. In a nearly neutral 1L WS2, trions and
      biexcitons possess large binding energies of ~ 10-15 and 45 meV, respectively.
      Moreover, our finding of electrically induced robust emission opens up a
      possibility to boost the luminous efficiency of emerging 1L TMD light emitting
      diodes.

PMID- 25560635
TI  - Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic
      hormone in critical illness: a prospective cohort study.
AB  - INTRODUCTION: Adrenal dysfunction may represent critical illness-related
      corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol
      response to exogenous adrenocorticotropic hormone (ACTH), but this concept and
      its clinical significance remain highly controversial. We studied the adrenal
      response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH
      ratio, a measure of adrenal sensitivity, and of clinical variables, during
      critical illness and recovery from the acute phase. METHODS: We prospectively
      included 59 consecutive septic and nonseptic patients in the intensive care unit
      with treatment-insensitive hypotension in whom CIRCI was suspected; patients
      having received etomidate and prolonged corticosteroids were excluded. An ACTH
      test (250 MUg) was performed, followed by a second test after >=7 days in acute
      phase survivors. Serum total and free cortisol, ACTH, and clinical variables were
      assessed. Patients were divided according to responses (delta, Delta) of cortisol
      to ACTH at the first and second tests. RESULTS: Patients with low (<250 nM) Delta
      cortisol (n = 14 to 17) had higher baseline cortisol and ACTH but lower
      cortisol/ACTH ratios than patients with a normal Delta cortisol (>=250 nM) in the
      course of time. A low Delta cortisol in time was associated with more-severe
      disease, culture-positive sepsis, and prolonged activated prothrombin time.
      Results for free cortisol were similar. CONCLUSIONS: Even though the pituitary
      adrenal axis is activated after stress during critical illness, diminished
      adrenal sensitivity to endogenous ACTH predicts a low increase of cortisol to
      exogenous ACTH, suggesting adrenal dysfunction, irrespective of the stage of
      disease. The data further suggest a role of disease severity and culture-positive
      sepsis.

PMID- 25560636
TI  - Could yoga practice improve treatment-related side effects and quality of life
      for women with breast cancer? A systematic review and meta-analysis.
AB  - AIM: To determine if yoga as a complementary and alternative therapy was
      associated with enhanced health and treatment-related side effects in patients
      with breast cancer. This systematic review examines whether yoga practice
      provides any measurable benefit, both physically and psychologically, for women
      with breast cancer. METHODS: PubMed, EMBASE and the Cochrane Library for
      randomized controlled trials (RCTs) throughout June 2013. We evaluated the
      quality of the included studies by the Cochrane Handbook 5.2 standards and
      analyzed the data using the Stata software, version 10.0. Meta-regression and
      subgroup analysis were also performed to identify additional predictors of
      outcome and to assess heterogeneity. RESULTS: Sixteen RCTs with a total of 930
      participants were included. Comparing yoga groups to control groups, there was a
      statistically significant difference in overall health-related quality of life,
      depression, anxiety and gastrointestinal symptoms. Meta-regression analyses
      revealed that the duration of yoga practice and type of control group partly
      explained the heterogeneity. Subgroup analyses revealed that yoga had a positive
      effect on anxiety only when it had been practiced for longer than 3 months. Only
      the wait-list control group showed an effect of yoga on physical well-being.
      CONCLUSION: The current evidence demonstrates that yoga practice could be
      effective in enhancing health and managing some treatment-related side effects
      for patients recovering from breast cancer. In future clinical studies,
      clinicians should consider the patient's wishes along with the current best
      evidence of the effects of yoga practice in their clinical decision-making.

PMID- 25560637
TI  - Critical evaluation of changes in the ratio of insoluble bound to soluble
      phenolics on antioxidant activity of lentils during germination.
AB  - A new indicator, the ratio of insoluble bound phenolics (IBPs) to soluble
      phenolics (SPs), is suggested as an effective means to monitor changes in the
      antioxidant activity of lentils during germination. This indicator may be used to
      monitor other process-induced changes in antioxidant potential of food phenolics
      in other foods. The antioxidant activity of SPs, IBPs, and total value, the sum
      of both free and esterified phenolics, of germinated CDC Richlea lentil variety
      was evaluated for 4 days. Total phenolic content (TPC), total flavonoid content
      (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, and 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation scavenging ability
      were employed to record antioxidant activities. An incremental increase in IBPs
      was found in TPC, TFC, DPPH, and ABTS radical cation scavenging ability, whereas
      SPs showed a declining trend in TFC, DPPH, and ABTS, except TPC during 4 days of
      germination. The ratio of IBPs to SPs increased using most methods, and this may
      be possibly due to the changes of phenolic compound formation from soluble into
      insoluble bound form during germination process. The ratio can be used as a novel
      method for monitoring process-induced changes in the antioxidant activity of
      foods. 

PMID- 25560638
TI  - Elevated circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) levels are
      associated with neuroendocrine differentiation in castration resistant prostate
      cancer.
AB  - BACKGROUND: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a 28.5 kDa
      secreted glycoprotein that inhibits matrix metalloproteinase (MMP) activity. Our
      group has previously shown that elevated plasma TIMP-1 levels predict poor
      survival in metastatic castration-resistant prostate cancer (CRPC) patients;
      however, the underlying source and impact of elevated circulating TIMP-1 protein
      is unknown. METHODS: In this study, we used qRT-PCR, ELISA and
      immunohistochemistry to evaluate TIMP-1 expression in androgen-sensitive and
      resistant prostate cancer (PC) cell lines, tumor tissues and patient sera, and to
      correlate TIMP-1 levels to expression of chromogranin A (CGA), an established
      marker of neuroendocrine differentiation (NED). We also explored the relationship
      between TIMP-1 overexpression and induction of NED by overexpressing TIMP-1 in
      androgen-sensitive LNCaP cells, as well as by inducing NED of LNCaP cells with IL
      6. RESULTS: Patients with CRPC have significantly higher serum TIMP-1 levels
      compared to patients with hormone-sensitive disease. Although circulating TIMP-1
      levels were increased, peripheral blood cells were not the source of elevation.
      Instead, elevated TIMP-1 expression was associated with higher expression of CGA
      in both blood and metastatic tumor tissue. We further show that androgen receptor
      (AR) and PSA non-expressing prostate cancer cell lines known to display NED
      phenotypes such as PC-3, PC-3M, and DU145 cells, expressed high levels of TIMP-1,
      in contrast to AR (+) and PSA (+) adenocarcinoma cell lines such as LNCaP, VCaP,
      and LAPC-4, which had barely detectable levels of TIMP-1. In addition, ectopic
      overexpression of TIMP-1 in LNCaP cells did not induce NED. However, TIMP-1 mRNA
      expression was elevated >10-fold during IL-6-induced NED of LNCaP cells,
      suggesting that TIMP-1 overexpression accompanies, but is not the driving force
      for NED. Finally, we show that conditioned media from androgen-resistant PC-3, PC
      3M, and DU145 cells induced TIMP-1 mRNA expression in primary prostate stromal
      fibroblasts in an ERK and NF-kappaB dependent manner. CONCLUSIONS: We provide in
      vitro and clinical evidence to support the association between NED and elevated
      circulating TIMP-1 expression in CRPC. Our observation supports further
      evaluation of TIMP-1 as a tissue and serum biomarker for NED in CRPC.

PMID- 25560639
TI  - Expression of claudins in human clear cell renal cell carcinoma.
AB  - The current study investigated the expression of claudins 1, 5 and 16 in human
      clear cell renal cell carcinoma (CCRCC) and the impact of claudin-16 on kidney
      cancer cells. Levels of claudin transcripts were assessed using quantitative
      reverse transcription-polymerase reaction and proteins were examined by
      immunohistochemical methods. Human kidney epithelial cell HEK293 and human kidney
      cancer cell line UMRC2 were also used in the study. Human kidney tissues
      expressed high levels of claudin-1 and in particular claudin-16, but were
      negative for claudin-5. Late-stage kidney carcinomas tended to express low levels
      of claudin-1 and claudin-16. UMRC2 cells, highly positive for claudin-16, were
      transfected with an anti-claudin-16 transgene, which resulted in significant
      reduction in both transepithelial resistance and cell matrix adhesion compared to
      control cells. When HEK293 cells, negative for expression of claudin-16, were
      forced to express claudin-16, the cells showed a marked increase in
      transepithelial resistance and to some degree in cell matrix adhesion. In
      conclusion, the present study showed that kidney tissue and CCRCC tissues highly
      expressed claudin-16 and claudin-1, and that claudin-16 has a profound impact on
      barrier function and cell adhesion in kidney cancer cells. 

PMID- 25560640
TI  - Phenome-genome association studies of pancreatic cancer: new targets for therapy
      and diagnosis.
AB  - BACKGROUND: Pancreatic cancer, has a very high mortality rate and requires novel
      molecular targets for diagnosis and therapy. Genetic association studies over
      databases offer an attractive starting point for gene discovery. MATERIALS AND
      METHODS: The National Center for Biotechnology Information (NCBI) Phenome Genome
      Integrator (PheGenI) tool was enriched for pancreatic cancer-associated traits.
      The genes associated with the trait were characterized using diverse
      bioinformatics tools for Genome-Wide Association (GWA), transcriptome and
      proteome profile and protein classes for motif and domain. RESULTS: Two hundred
      twenty-six genes were identified that had a genetic association with pancreatic
      cancer in the human genome. This included 25 uncharacterized open reading frames
      (ORFs). Bioinformatics analysis of these ORFs identified putative druggable
      proteins and biomarkers including enzymes, transporters and G-protein-coupled
      receptor signaling proteins. Secreted proteins including a neuroendocrine factor
      and a chemokine were identified. Five out of these ORFs encompassed non coding
      RNAs. The ORF protein expression was detected in numerous body fluids, such as
      ascites, bile, pancreatic juice, milk, plasma, serum and saliva. Transcriptome
      and proteome analyses showed a correlation of mRNA and protein expression for
      nine ORFs. Analysis of the Catalogue of Somatic Mutations in Cancer (COSMIC)
      database revealed a strong correlation across copy number variations and mRNA
      over-expression for four ORFs. Mining of the International Cancer Gene Consortium
      (ICGC) database identified somatic mutations in a significant number of
      pancreatic patients' tumors for most of these ORFs. The pancreatic cancer
      associated ORFs were also found to be genetically associated with other
      neoplasms, including leukemia, malignant melanoma, neuroblastoma and prostate
      carcinomas, as well as other unrelated diseases and disorders, such as
      Alzheimer's disease, Crohn's disease, coronary diseases, attention deficit
      disorder and addiction. CONCLUSION: Based on Genome-Wide Association Studies
      (GWAS), copy number variations, somatic mutational status and correlation of gene
      expression in pancreatic tumors at the mRNA and protein level, expression
      specificity in normal tissues and detection in body fluids, six ORFs emerged as
      putative leads for pancreatic cancer. These six targets provide a basis for
      accelerated drug discovery and diagnostic marker development for pancreatic
      cancer.

PMID- 25560641
TI  - Epigenetic Silencing of GNMT Gene in Pancreatic Adenocarcinoma.
AB  - BACKGROUND/AIM: Although pancreatic ductal adenocarcinoma (PDAC) remains a major
      challenge for therapy, biomarkers for early detection are lacking. Epigenetic
      silencing of tumor suppressor genes is a majorcontributor to neoplastic
      transformation. The aim of this study was to identify new factors involved in
      PDAC progression. The GNMT gene possesses CpG islands in the promoter region and
      is important in methyl-group metabolism and in maintaining a normal methylation
      status of the genome. MATERIALS AND METHODS: To test the hypothesis whether GNMT
      is epigenetically regulated in PDAC, we evaluated the GNMT gene expression and
      promoter methylation status in 30 paired samples of PDAC and normal pancreatic
      tissue. RESULTS: We found significantly higher methylation frequencies (p<0.001)
      in PDACs (2.82-100%; median, 36.05%) than in controls (0.28-14.02%; median,
      4.39%). The GNMT gene expression was decreased in PDACs compared to normal
      pancreatic tissues in 26/30 cases (86.67%). Furthermore, we showed that treatment
      with 5-aza-2-deoxycytidine (5-aza-dC) increased GNMT mRNA expression and
      decreased viability in PDAC cells. CONCLUSION: Collectively, these data indicate
      that GNMT is aberrantly methylated in PDAC representing, thus, a potential major
      mechanism for gene silencing. Methylation of GNMT gene is directly correlated
      with disease stage and with tumor grade indicating that these epigenetic effects
      may be important regulators of PDAC progression.

PMID- 25560642
TI  - Usefulness of nanofluidic digital PCR arrays to quantify T790M mutation in EGFR
      mutant lung adenocarcinoma.
AB  - AIM: The present pilot study assessed the usefulness of nanofluidic digital
      polymerase chain reaction (PCR) arrays in epidermal growth factor receptor (EGFR)
      mutant lung adenocarcinoma after tyrosine kinase inhibitor (TKI) resistance.
      PATIENTS AND METHODS: We enrolled 12 patients with primary lung adenocarcinoma
      with sensitive EGFR mutation-confirmed T790M status by re-biopsy after TKI
      resistance. Nanofluidic digital PCR arrays were used to quantify T790M in genomic
      DNA from the pre-treatment primary site and in serum cell-free DNA (cfDNA).
      RESULTS: On digital PCR, quantified T790M at the pre-treatment primary site was
      higher in re-biopsy-positive T790M patients (n=4) than in re-biopsy-negative
      patients (n=8) (0.78%+/-0.36% vs. 0.07%+/-0.09%, p<0.01). T790M at the pre
      treatment primary site correlated with progression-free survival (PFS) after
      gefitinib therapy (r=0.67, p=0.016). CONCLUSION: Use of digital PCR to quantify
      T790M at the primary site of EGFR-mutant lung adenocarcinoma predicted T790M
      emergence in re-biopsies after TKI resistance and PFS after gefitinib therapy.

PMID- 25560643
TI  - Quantitative proteomics of bronchoalveolar lavage fluid in lung adenocarcinoma.
AB  - BACKGROUND: The most commonly reported primary lung cancer subtype is
      adenocarcinoma, which is associated with a poor prognosis and short survival.
      Proteomic studies on human body fluids such as bronchoalveolar lavage fluid
      (BALF) have become essential methods for biomarker discovery, examination of
      tumor pathways and investigation of potential treatments. AIM: This study used
      quantitative proteomics to investigate the up-regulation of novel proteins in
      BALF from patients with primary lung adenocarcinoma in order to identify
      potential biomarkers. MATERIALS AND METHODS: BALF samples from individuals with
      and without primary lung adenocarcinoma were analyzed using liquid chromatography
      mass spectrometry. RESULTS: One thousand and one hundred proteins were
      identified, 33 of which were found to be consistently overexpressed in all lung
      adenocarcinoma samples compared to non-cancer controls. A number of overexpressed
      proteins have been previously shown to be related to lung cancer progression
      including S100-A8, annexin A1, annexin A2, thymidine phosphorylase and
      transglutaminase 2. CONCLUSION: The overexpression of a number of specific
      proteins in BALF from patients with primary lung adenocarcinoma may be used as a
      potential biomarker for lung adenocarcinoma.

PMID- 25560645
TI  - The pathos of the closet and the generations: gay professors and their students
      during and post gay liberation in the United States.
AB  - This article focuses on gay professor-student relationships in the United States,
      during and post gay liberation. Exploring personal writings, student periodicals,
      and academic documents between the late 1960s and the 1990s, I argue that
      interactions between gay professors and their students illuminate an ambiguous
      affectionate relationship wherein the closeness was based just as much on
      different generational sensibilities as the individuals themselves. Further, I
      show that these relationships suggest a therapeutic potential to education
      through the articulation of personal knowledge in the classroom, one that was
      increasingly open to challenge in the 1980s and 1990s. 

PMID- 25560644
TI  - Telaprevir enhances ribavirin-induced anaemia through renal function impairment.
AB  - BACKGROUND: Alterations in renal function have been described with telaprevir
      (TVR). We examined the relationship between ribavirin (RBV) trough concentration
      (C), estimated glomerular filtration rate (eGFR) and severe anaemia, before and
      after TVR introduction in HIV-HCV-coinfected patients included in ANRS HC26
      TelapreVIH study. METHODS: 69 HIV-HCV genotype-1 coinfected patients received 4
      weeks of pegylated interferon (PEG-IFN)-alpha2a/RBV, followed by 12 weeks of
      TVR/PEG-IFN/RBV, then 32 to 56 weeks of PEG-IFN/RBV. RBV C was determined at week
      (W)4, W8 and W20/24. eGFR was estimated by the Modification of the Diet in Renal
      Disease (MDRD) equation. Severe anaemia was defined as haemoglobin <70 g/l, RBV
      dose reduction, prescription of erythropoietin or blood transfusion. RESULTS: 67
      patients were analysed. eGFR remained normal between baseline (97.9 ml/min) and
      W4 (103.4 ml/min), declined to 86.3 ml/min at W8 (P<0.0001), stabilized until W16
      and increased back to baseline level at W20 (98.4 ml/min). RBV C increased from
      1.88 mg/l at W4 to 2.88 mg/l at W8 (P<0.0001), then decreased to 2.73 mg/l at
      week 20/24 (P=0.015). An inverse correlation was observed between W8 eGFR and W8
      RBV C (r2=0.429; P=0.0005). RBV C>=3 mg/l was observed in 12% of patients at W4,
      45% at W8 (P<0.0001) and 38% at W20/24 (P=0.0005). Severe anaemia was observed in
      23.9% of patients at W4 and 45.3% at W8. RBV C>=3 mg/l at W8 (OR 7.7 [95% CI 2.2,
      27.4]) and baseline haemoglobin <150 g/l (OR 6.4 [1.7, 23.8]) were independently
      associated with W8 severe anaemia. CONCLUSIONS: Association of TVR to PEG-IFN/RBV
      was associated with a decrease in eGFR and increase in RBV C, leading to severe
      anaemia in 45% of patients.

PMID- 25560646
TI  - Antimicrobial activity of human beta-defensins against lactic acid bacteria.
AB  - In this study, we evaluated the antimicrobial activity of human beta-defensin-1
      (hBD-1), human beta-defensin-2 (hBD-2) and human beta-defensin-3 (hBD-3) against
      three internationally common probiotic strains of lactic acid bacterium. Our
      results indicated that hBD-1, hBD-2 and hBD-3 at the range of 0.08-10 MUg/mL do
      not have obvious antimicrobial activity against these strains. Viability of
      Bifidobacterium longum JDM301 (B. longum JDM301), Bifidobacterium lactis HN019
      (B. lactis HN019) and Lactobacillus rhamnosus GG (LGG) were still very high even
      at concentration of 10 MUg hBD/mL. Then, we explored the mechanism of resistance
      by using carbonyl cyanide 3-chlorophenylhydrazone (CCCP) to inhibit efflux pumps.
      In the presence of CCCP, hBD-1, hBD-2 and hBD-3 exhibited enhanced antibacterial
      effect against B. longum JDM301 and B. lactis HN019, but not against LGG. Efflux
      pumps in B. longum JDM301 and B. lactis HN019 may partly contribute to their
      resistance to hBD-1, hBD-2, and hBD-3.

PMID- 25560647
TI  - The effects of serum apolipoprotein E genetic variants and concentration on serum
      lipid parameters in haemodialysis patients.
AB  - OBJECTIVES: Many epidemiological studies demonstrate that the apolipoprotein E
      gene (ApoE) is an important candidate gene for playing key roles in the
      development of haemodialysis (HD). The purpose of this study is to evaluate the
      effects of ApoE genetic variants and concentration on serum lipid parameters in
      HD. METHODS: A total of 288 HD patients and 292 healthy controls were enrolled in
      this case-control study. The genotypes of ApoE genetic variants were investigated
      through the created restriction site-polymerase chain reaction and DNA-sequencing
      methods. KEY FINDINGS: Our data indicated that the levels of triglyceride, total
      cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, apolipoprotein A-I (ApoA-I), ApoB, ApoE, lipoprotein (a) (Lp(a)) of
      mutant genotypes in ApoE c.61G > A and c.761T > A genetic variants were different
      from those subjects with wild genotype in HD patients and healthy controls.
      CONCLUSIONS: These preliminary results from this study suggest that the ApoE
      genetic variants and concentration could affect the serum lipid parameters in HD
      and could be risk factors for evaluating HD.

PMID- 25560648
TI  - Nanostructured lipid carriers as novel drug delivery system for lung cancer gene
      therapy.
AB  - CONTEXT: Nanostructured lipid carriers (NLC) are potentially good colloidal drug
      carriers for gene delivery. They are advised to be the second lifetime of lipid
      nanocarriers. OBJECTIVE: The aim of this study is to develop novel modified NLC
      as nanomedicine for delivery of plasmid-containing enhanced green fluorescence
      protein (pEGFP). This system could target the lung cancer cells through receptor
      mediated pathways to increase the nuclear uptake of genetic materials. METHODS:
      In the present study, pEGFP-loaded NLC (NLC/pEGFP) were prepared. Transferrin
      (Tf) containing ligands were used for the surface coating of the vectors. In
      vitro transfection efficiency of the modified vectors was evaluated in human
      alveolar adenocarcinoma cell line (A549 cells) and in vivo transfection
      efficiency of the modified vectors was evaluated on mice bearing A549 cells
      model. RESULTS: Tf-modified NLC/pEGFP (Tf-NLC/pEGFP) has a particle size of 157
      nm, and ~ 82% of gene loading quantity. Tf-NLC/pEGFP displayed remarkably higher
      transfection efficiency than non-modified NLC/pEGFP both in vitro and in vivo.
      CONCLUSION: The results demonstrate that the novel NLC gene delivery system
      offers an effective strategy for lung cancer gene therapy.

PMID- 25560649
TI  - The azomethine ylide route to amine C-H functionalization: redox-versions of
      classic reactions and a pathway to new transformations.
AB  - Conspectus Redox-neutral methods for the functionalization of amine alpha-C-H
      bonds are inherently efficient because they avoid external oxidants and
      reductants and often do not generate unwanted byproducts. However, most of the
      current methods for amine alpha-C-H bond functionalization are oxidative in
      nature. While the most efficient variants utilize atmospheric oxygen as the
      terminal oxidant, many such transformations require the use of expensive or toxic
      oxidants, often coupled with the need for transition metal catalysts. Redox
      neutral amine alpha-functionalizations that involve intramolecular hydride
      transfer steps provide viable alternatives to certain oxidative reactions. These
      processes have been known for some time and are particularly well suited for
      tertiary amine substrates. A mechanistically distinct strategy for secondary
      amines has emerged only recently, despite sharing common features with a range of
      classic organic transformations. Among those are such widely used reactions as
      the Strecker, Mannich, Pictet-Spengler, and Kabachnik-Fields reactions, Friedel
      Crafts alkylations, and iminium alkynylations. In these classic processes,
      condensation of a secondary amine with an aldehyde (or a ketone) typically leads
      to the formation of an intermediate iminium ion, which is subsequently attacked
      by a nucleophile. The corresponding redox-versions of these transformations
      utilize identical starting materials but incorporate an isomerization step that
      enables alpha-C-H bond functionalization. Intramolecular versions of these
      reactions include redox-neutral amine alpha-amination, alpha-oxygenation, and
      alpha-sulfenylation. In all cases, a reductive N-alkylation is effectively
      combined with an oxidative alpha-functionalization, generating water as the only
      byproduct. Reactions are promoted by simple carboxylic acids and in some cases
      require no additives. Azomethine ylides, dipolar species whose usage is
      predominantly in [3 + 2] cycloadditions and other pericyclic processes, have been
      identified as common intermediates. Extension of this chemistry to amine
      alpha,beta-difunctionalization has been shown to be possible by way of converting
      the intermediate azomethine ylides into transient enamines. This Account details
      the evolution of this general strategy and the progress made to date. Further
      included is a discussion of related decarboxylative reactions and transformations
      that result in the redox-neutral aromatization of (partially) saturated cyclic
      amines. These processes also involve azomethine ylides, reactive intermediates
      that appear to be far more prevalent in condensation chemistry of amines and
      carbonyl compounds than previously considered. In contrast, as exemplified by
      some redox transformations that have been studied in greater detail, iminium ions
      are not necessarily involved in all amine/aldehyde condensation reactions. 

PMID- 25560650
TI  - N-Acetyl-beta-D-glucosaminidase activity in feral Carcinus maenas exposed to
      cadmium.
AB  - Cadmium is a priority hazardous substance, persistent in the aquatic environment,
      with the capacity to interfere with crustacean moulting. Moulting is a vital
      process dictating crustacean growth, reproduction and metamorphosis. However, for
      many organisms, moult disruption is difficult to evaluate in the short term, what
      limits its inclusion in monitoring programmes. N-acetyl-beta-D-glucosaminidase
      (NAGase) is an enzyme acting in the final steps of the endocrine-regulated
      moulting cascade, allowing for the cast off of the old exoskeleton, with
      potential interest as a biomarker of moult disruption. This study investigated
      responses to waterborne cadmium of NAGase activity of Carcinus maenas originating
      from estuaries with different histories of anthropogenic contamination: a low
      impacted and a moderately polluted one. Crabs from both sites were individually
      exposed for seven days to cadmium concentrations ranging from 1.3 to 2000 MUg/L.
      At the end of the assays, NAGase activity was assessed in the epidermis and
      digestive gland. Detoxification, antioxidant, energy production, and oxidative
      stress biomarkers implicated in cadmium metabolism and tolerance were also
      assessed to better understand differential NAGase responses: activity of
      glutathione S-transferases (GST), glutathione peroxidase (GPx) glutathione
      reductase (GR), levels of total glutathiones (TG), lipid peroxidation (LPO),
      lactate dehydrogenase (LDH), and NADP(+)-dependent isocitrate dehydrogenase
      (IDH). Animals from the moderately polluted estuary had lower NAGase activity
      both in the epidermis and digestive gland than in the low impacted site. NAGase
      activity in the epidermis and digestive gland of C. maenas from both estuaries
      was sensitive to cadmium exposure suggesting its usefulness for inclusion in
      monitoring programmes. However, in the digestive gland NAGase inhibition was
      found in crabs from the less impacted site but not in those from the moderately
      contaminated one. Altered glutathione levels were observed in cadmium-treated
      crabs from the contaminated site possibly conferring enhanced tolerance to these
      animals through its chelator action. Investigation of enhanced tolerance should
      thus be accounted for in monitoring programmes employing NAGase as biomarker to
      avoid data misinterpretation.

PMID- 25560651
TI  - Evaluation of the sensitivity, responsiveness and reproducibility of primary
      rainbow trout hepatocyte vitellogenin expression as a screening assay for
      estrogen mimics.
AB  - Vitellogenin (Vtg) induction in primary fish hepatocytes has been proposed as an
      in vitro screening assay for ER agonists and antagonists, but has not yet been
      used extensively as a high-throughput screening tool due to poor reproducibility,
      sensitivity and overall feasibility. The present work has evaluated the role of
      seasonal variation, normalization, optimal culture and assay conditions on the
      sensitivity, responsiveness and reproducibility of in vitro vtg gene mRNA and
      protein expression in rainbow trout (Oncorhynchus mykiss) primary hepatocytes
      using the xenoestrogen 17alpha-ethynylestradiol (EE2) as a test chemical. The
      results show that primary hepatocytes display a relatively high individual and
      seasonal variation in both Vtg mRNA and protein induction potential, although
      less variance was observed in assay sensitivity. Data normalization of assay
      response to maximum (3 nM EE2) and minimum (DMSO) Vtg production dramatically
      reduced this variance and led to improved assay reproducibility. A time-dependent
      response was observed both for mRNA and protein expression, reaching maximum Vtg
      induction after 96 h of exposure, although reproducible concentration response
      curves for both Vtg mRNA and protein could be obtained already after 48 h. A need
      for chemical re-exposure of the hepatocytes was identified to be important for
      sustaining exposure concentrations in extended studies (>48 h), whereas different
      plate formats (96, 24 or 6 wells) did not affect the bioassay performance. In
      conclusion, standardization of hepatocyte bioassay and test conditions as well as
      data-normalization procedures are proposed to be instrumental for more consistent
      and comparable results in future use of this in vitro assay.

PMID- 25560652
TI  - The optimal therapy of calcineurin inhibitors for pregnancy in kidney
      transplantation.
AB  - We investigated the effects of pregnancy and delivery on renal function in
      transplant recipients and the relationship between doses of immunosuppressants
      and blood drug levels during pregnancy in 75 women with 88 deliveries.
      Significant serum creatinine elevation (> 0.5 mg/dL) was found in eight
      deliveries. In the remaining 80 cases, serum creatinine was reduced by an average
      of 0.14 mg/dL and returned to pre-pregnant levels after delivery. Tacrolimus was
      used in 28 deliveries and cyclosporine in others. Tacrolimus blood trough level
      declined from 5.8 +/- 2.8 ng/mL 12 months before delivery to 4.2 +/- 1.8 ng/mL at
      second trimester; therefore, drug dose was increased from 4.1 +/- 1.9 mg/d at
      first trimester to 5.5 +/- 2.5 mg/d at delivery. Similarly, cyclosporine levels
      were 125.1 +/- 65.1 ng/mL 12 months before delivery and 75.4 +/- 35.0 ng/mL at
      second trimester resulting in dose elevation from 183.0 +/- 71.8 mg/d at first
      trimester to 225.4 +/- 85.1 mg/d at delivery. Renal function in female kidney
      transplant recipients improved slightly during pregnancy and returned to pre
      pregnant level after delivery. The dose elevation of calcineurin inhibitor by
      approximately 20-25% should be considered during gestational period to maintain
      optimal blood drug level.

PMID- 25560653
TI  - Managing outbreaks of invasive species--a new method to prioritize preemptive
      quarantine efforts across large geographic regions.
AB  - In pest risk assessment it is frequently necessary to make time-critical
      decisions regarding management of expanding pest populations. When an invasive
      pest outbreak is expanding rapidly, preemptive quarantine of areas that are under
      imminent threat of infestation is one of only a few available management tools
      that can be implemented quickly to help control the expansion. The preemptive
      quarantine of locations that surround an infested area also acts as a safeguard
      to counteract the risk of failed detections of the pest in field surveys. In this
      paper, we present a method that assesses the suitability of preemptive quarantine
      measures at the level of small geographical subdivisions (U.S. counties). The
      cost of a preemptive quarantine in a given county is weighed against the
      protective benefit of delaying the spread of an outbreak to other neighboring
      counties. We demonstrate the approach with a decision support model that
      estimates the suitability of preemptive quarantine across multiple counties that
      surround areas infested with the emerald ash borer (Agrilus planipennis Fairmaire
      (EAB), Coleoptera: Buprestidae), an emerging major threat to ash tree species
      (Fraxinus spp.) in North America. The model identifies the U.S. counties where
      the installation of preemptive quarantine would most effectively slow the spread
      of EAB populations and reduce risk to high-value areas. 

PMID- 25560654
TI  - Treatment of amoxicillin by O3/Fenton process in a rotating packed bed.
AB  - In this study, simulated amoxicillin wastewater was treated by the O3/Fenton
      process in a rotating packed bed (RPB) and the results were compared with the
      Fenton process and the O3 followed by Fenton (O3 + Fenton) process. The chemical
      oxygen demand (COD) removal rate and the ratio of 5-day biological oxygen demand
      to chemical oxygen demand (BOD5/COD) in the O3/Fenton process were approximately
      17% and 26%, respectively, higher than those in the O3 + Fenton process with an
      initial pH of 3. The COD removal rate of the amoxicillin solution reached maximum
      at the Fe(II) concentration of 0.6 mM, temperature of 25  degrees C, rotation
      speed of 800 rpm and initial pH of 3. The BOD5/COD of the amoxicillin solution
      increased from 0 to 0.38 after the solution was treated by the O3/Fenton process.
      Analysis of the intermediates indicated that the pathway of amoxicillin
      degradation in the O3/Fenton process was similar to that in the O3 + Fenton
      process. Contrast experiment results showed that amoxicillin degradation was
      significantly intensified in the RPB. 

PMID- 25560655
TI  - Modeling raindrop strike performance on copper wash-off from vine leaves.
AB  - Copper lost in foliar wash-off from vine leaves treated with Cu-based fungicides
      was analyzed with a single-drop rainfall simulator. The temporal losses of the
      particulate Cu (CuP) and the solution Cu (CuS) from raindrop strikes on leaves
      were modeled using a Poisson point process. This model estimated maximum
      detachment rates of 0.82 ng CuP and 0.033 ng CuS per raindrop. The total amount
      of Cu (CuT) in the leaves before rainfall ranged between 0.4 and 4.4 g Cu kg(-1)
      dry weight. Wash-off reduced the amount of CuT present in the leaves by 0.6 g kg(
      1). Particulate losses of CuT ranged from 75 to 90%, while soluble losses of CuT
      ranged from 10 to 25%. The kinetic energy of the raindrops influenced the loss of
      CuS but not the loss of CuP. The Poisson point approach can provide an
      interesting starting point to model non-point source pollution produced from
      agricultural chemicals washed-off by rain. 

PMID- 25560656
TI  - Impact of land-use on carbon storage as dependent on soil texture: evidence from
      a desertified dryland using repeated paired sampling design.
AB  - Desertification resulting from land-use affects large dryland areas around the
      world, accompanied by carbon loss. However it has been difficult to interpret
      different land-use contributions to carbon pools owing to confounding factors
      related to climate, topography, soil texture and other original soil properties.
      To avoid such confounding effects, a unique systematic and extensive repeated
      design of paired sampling plots of different land-use types was adopted on Ordos
      Plateau, N China. The sampling enabled to quantify the effects of the predominant
      land-use types on carbon storage as dependent on soil texture, and to define the
      most promising land-use choices for carbon storage, both in grassland on sandy
      soil and in desert grassland on brown calcareous soil. The results showed that
      (1) desertification control should be an effective measure to improve the carbon
      sequestration in sandy grassland, and shrub planting should be better than grass
      planting; (2) development of man-made grassland should be a good choice to solve
      the contradictions of ecology and economy in desert grassland; (3) grassland on
      sandy soil is more vulnerable to soil degradation than desert grassland on brown
      calcareous soil. The results may be useful for the selection of land-use types,
      aiming at desertification prevention in drylands. Follow-up studies should
      directly investigate the role of soil texture on the carbon storage dynamic
      caused by land-use change. 

PMID- 25560657
TI  - The contribution of household chemicals to environmental discharges via
      effluents: combining chemical and behavioural data.
AB  - Increased concentrations and loads of soluble, bioavailable forms of phosphorus
      (P) are a major cause of eutrophication in streams, rivers and lakes in many
      countries around the world. To implement P control measures, it is essential to
      identify P sources and their relative load contributions. A proportion of P
      loading generated from household wastewaters is derived from detergents yet the P
      compositions of the range of domestic detergents and their usage is poorly
      understood. To quantify P loads from household detergents, we analysed a large
      range of detergents and cleaning products commonly available in the UK and
      Europe, comparing regular and eco-labelled products. Chemical data were coupled
      with survey results on typical household detergents preferences and usage (n = 95
      households). We also determined whether the major and trace element signatures of
      these household detergents could potentially be used as anthropogenic tracers in
      watercourses. The greatest P concentrations were found for regular dishwasher
      detergents (43-131 mg P/g detergent) whilst the range of P in eco-labelled
      dishwasher detergents was much lower (0.7-9.1 mg P/g detergent). Other household
      cleaning groups contained relatively smaller P concentrations. Considering the
      survey results, detergents' total P loading generated from one household using
      either regular or eco labelled products, was 0.414 and 0.021 kg P/year,
      respectively. Given a household occupancy of 2.7, the P load from all detergent
      use combined was 0.154 kg P/person/year of which the dishwasher contribution was
      0.147 kg P/person/year. In terms of elemental signatures, (DWD) dishwasher
      detergents were significantly (P-value <0.001) different from other household
      cleaning products in their As, Na, TP, Si, Sr, SRP, Ti, Zn and Zr signatures. Na,
      P and B were all positively correlated with each other, indicating their
      potential use as a tracer suite for septic tank effluent in combination with
      other indices. We conclude that forthcoming legislation for reducing P contents
      in domestic laundry detergents will not address the dominant environmental P load
      from DWD and studies such as this are important in promoting and allowing
      scenarios of benefits from future legislation for DWD.

PMID- 25560658
TI  - Drought risk mapping of south-western state in the Indian peninsula - A web based
      application.
AB  - Application of geospatial technology is very shimmering in drought monitoring.
      Drought severity in crops for six northern districts of Kerala has been attempted
      using Geospatial Techniques. Normalized Difference Vegetation Index (NDVI) is the
      major parameter used to measure vegetation health obtained from MODIS, Terra
      satellite products MOD13Q1, MOD02QKM. The mean Normalized Difference Vegetation
      Index (NDVI) of Kerala state over 13 years was calculated. The daily anomalies of
      NDVI from its long term mean NDVI over the same period was determined based on
      which drought risk classification was done. High negative NDVI anomaly areas are
      susceptible to drought and the severity of drought risk on each crop can be
      identified using Land Use/Land Cover data. Overlaying daily NDVI Anomaly based
      drought risk map on land use/land cover map gives the drought risk for different
      crops. Based on this, a web application has been developed for Northern districts
      of Kerala state in India. This web application can be used to plan for drought
      management measures and can also serve as a database for drought analysis. 

PMID- 25560659
TI  - Influence of combined use of iodide and compost on Hg accumulation by Lepidium
      sativum L.
AB  - This study focuses on the influence of adding iodide (KI) and compost in
      different soil/compost ratios on the efficiency of Hg phytoextraction by Lepidium
      sativum L. Plant growth and non-enzymatic antioxidants are studied to understand
      metabolic plant adaptations to Hg stress during soil reclamation and their
      relations to Hg accumulation. Due to the use of relatively high chelant dosages
      in current plant-based soil remediation techniques and associated environmental
      risks, it is necessary to explore alternative approaches to the phytoextraction
      of Hg from contaminated soils. The results show a coordinated increase in non
      enzymatic antioxidants in plants cultivated in growing media containing polluted
      soil, compost and KI. This indicates that the non-enzymatic antioxidative defence
      system of L. sativum L. is involved in its strategy to survive conditions of
      mercury-induced stress. Adding compost and iodide to Hg polluted soil also
      increases the total accumulation of Hg by L. sativum L. and the translocation of
      pollutants to aerial plant tissues. Simultaneous application of compost and KI
      promoted the Hg accumulation by L. sativum L. in a pot experiment. 

PMID- 25560660
TI  - Evaluation of two pesticide leaching models in an irrigated field cropped with
      corn.
AB  - Pesticide leaching models is an easy and cost effective method used in the
      prediction of surface and groundwater pollution. In this paper, the ability of
      two pesticide leaching models, MACRO and PEARL, to describe soil water dynamics
      and atrazine's transport through the soil profile was examined. The data used for
      the comparison was obtained from an experiment in an irrigated corn field in the
      plain of the Ardas River, in north-eastern Greece. Both models were parameterized
      using pedotransfer functions, field and laboratory data. The uncalibrated
      simulation showed several discrepancies, therefore the retention curve and the
      sorption parameters were calibrated according to the trial and error method. The
      comparison of both models indicated that soil water flow was described similarly.
      The simulated results of atrazine's concentration were evaluated and compared to
      the measured concentrations at specific depths, using statistical criteria.
      Atrazine transport was simulated in a satisfactory manner as confirmed by model
      efficiency (EF) values, that are very close to unit. Coefficient of residual mass
      (CRM) values for both models are positive, indicating that both models
      underestimate the measured data. MACRO estimated higher accumulated actual
      evapotranspiration values, and less percolated water from soil profile than
      PEARL, and as a result, change in water content was higher in the latter. PEARL
      also predicted that half the amount of the applied mass was decayed two days
      earlier than the day estimated by MACRO. Generally, MACRO simulated the fate of
      atrazine in soil better than PEARL. 

PMID- 25560661
TI  - Carbon prices and incentives for technological development.
AB  - There is concern that the carbon prices generated through climate policies are
      too low to create the incentives necessary to stimulate technological
      development. This paper empirically analyzes how the Swedish carbon dioxide (CO2)
      tax and the European Union emission trading system (EU ETS) have affected
      productivity development in the Swedish pulp and paper industry 1998-2008. A
      Luenberger total factor productivity (TFP) indicator is computed using data
      envelopment analysis. The results show that climate policy had a modest impact on
      technological development in the pulp and paper industry, and if significant it
      was negative. The price of fossil fuels, on the contrary, seems to have created
      important incentives for technological development. Hence, the results suggest
      that the carbon prices faced by the industry through EU ETS and the CO2 tax have
      been too low. Even though the data for this study is specific for Sweden, the
      models and results are applicable internationally. When designing policy to
      mitigate CO2 emissions, it is vital that the policy creates a carbon price that
      is high enough - otherwise the pressure on technological development will not be
      sufficiently strong. 

PMID- 25560662
TI  - Time evolution of the general characteristics and Cu retention capacity in an
      acid soil amended with a bentonite winery waste.
AB  - The effect of bentonite waste added to a "poor" soil on its general
      characteristic and copper adsorption capacity was assessed. The soil was amended
      with different bentonite waste concentrations (0, 10, 20, 40 and 80 Mg ha(-1)) in
      laboratory pots, and different times of incubation of samples were tested (one
      day and one, four and eight months). The addition of bentonite waste increased
      the pH, organic matter content and phosphorus and potassium concentrations in the
      soil, being stable for P and K, whereas the organic matter decreased with time.
      Additionally, the copper sorption capacity of the soil and the energy of the Cu
      bonds increased with bentonite waste additions. However, the use of this type of
      waste in soil presented important drawbacks for waste dosages higher than 20 Mg
      ha(-1), such as an excessive increase of the soil pH and an increase of copper in
      the soil solution. 

PMID- 25560663
TI  - Using coal fly ash as a support for Mn(II), Co(II) and Ni(II) and utilizing the
      materials as novel oxidation catalysts for 4-chlorophenol mineralization.
AB  - In this work, Mn(II), Co(II) and Ni(II) were incorporated into waste coal fly ash
      used as a catalyst support by refluxing with the appropriate aqueous salt
      solution. The materials were calcined at 773-873 K for 5 h and the amount of
      divalent cations entering into the fly ash was determined by AAS measurements.
      Further characterization included estimation of oxides by XRF, structural
      properties by XRD, topographical features by SEM, surface functional groups by FT
      IR, surface area and pore dimensions by BET N2-adsorption isotherms. The
      efficiency of the materials as environmental oxidation catalysts were tested with
      respect to destruction of 4-chlorophenol (4-CP) in water in the presence of
      hydrogen peroxide. Considered as one of the most persistent, toxic and largely
      applied organic compound, 4-CP enters water from the effluents of petrochemical,
      plastic, pesticide, kraft mill and other organochemical industries and research
      centers. Wet oxidation of 4-CP was tested by varying the mole ratio of 4-CP and
      H2O2, catalyst load, temperature, reaction time, 4-CP concentration and pH.
      Oxidation of 4-CP (5 * 10(-3) M or 643 mg L(-1)) was 51.1% for Mn(II)-fly ash,
      58.3% for Co(II)-fly ash and 61.0% for Ni(II)-fly ash after 180 min at 323 K with
      4-CP: H2O2 mole ratio of 1:1. COD load of the reaction mixture (4-CP: 5 * 10(-3)
      M, H2O2: 5 * 10(-3) M, catalyst load: 1.0 g L(-1), temperature 323 K, reaction
      time 0-240 min) decreased from 1480 to 620, 380, and 140 mg L(-1) respectively
      after oxidation with Mn(II)-fly ash, Co(II)-fly ash and Ni(II)-fly ash (overall
      COD reduction was 58.0, 74.3 and 90.5% respectively). The oxidation followed
      second order kinetics with the average rate coefficient of 7.9, 1.3 and 1.2 L
      mol(-1) min(-1) for Mn(II)-, Co(II)- and Ni(II)-fly ash. Increase in H2O2: 4-CP
      mole ratio from 1:1 to 20:1 (reaction time 300 min, catalyst load 1.0 g L(-1))
      enhanced destruction from 52.1 to 95.6% for Mn(II)-fly ash, 58.3-95.6% for Co(II)
      fly ash and from 60.4 to 94.8% for Ni(II)-fly ash. The oxidation increased with
      catalyst load but very high loads were not effective. Low pH favored the
      oxidation, but the catalysts performed well at the pH of aqueous 4-CP solution. A
      mechanism for the reactions is suggested based on the analysis of the products of
      oxidation.

PMID- 25560664
TI  - Flocculation behavior and mechanism of bioflocculant produced by Aspergillus
      flavus.
AB  - In this study, the flocculation behavior and mechanism of a cation-independent
      bioflocculant IH-7 produced by Aspergillus flavus were investigated. Results
      showed 91.6% was the lowest flocculating rate recorded by IH-7 (0.5 mg L(-1)) at
      pH range 4-8. Moreover, IH-7 showed better flocculation performance than
      polyaluminum chloride (PAC) at a wide range of flocculant concentration (0.06-25
      mg L(-1)), temperature (5-45  degrees C) and salinity (10-60% w/w). The current
      study found that cation addition did not significantly enhance the flocculating
      rate and IH-7 is a positively charged bioflocculant. These findings suggest that
      charge neutralization is the main flocculation mechanism of IH-7 bioflocculant.
      IH-7 was significantly used to flocculate different types of suspended solids
      such as activated carbons, kaolin clays, soil solids and yeast cells. 

PMID- 25560665
TI  - White matter abnormalities of microstructure and physiological noise in
      schizophrenia.
AB  - White matter abnormalities in schizophrenia have been revealed by many imaging
      techniques and analysis methods. One of the findings by diffusion tensor imaging
      is a decrease in fractional anisotropy (FA), which is an indicator of white
      matter integrity. On the other hand, elevation of metabolic rate in white matter
      was observed from positron emission tomography (PET) studies. In this report, we
      aim to compare the two structural and functional effects on the same subjects.
      Our comparison is based on the hypothesis that signal fluctuation in white matter
      is associated with white matter functional activity. We examined the variance of
      the signal in resting state fMRI and found significant differences between
      individuals with schizophrenia and non-psychiatric controls specifically in white
      matter tissue. Controls showed higher temporal signal-to-noise ratios clustered
      in regions including temporal, frontal, and parietal lobes, cerebellum, corpus
      callosum, superior longitudinal fasciculus, and other major white matter tracts.
      These regions with higher temporal signal-to-noise ratio agree well with those
      showing higher metabolic activity reported by studies using PET. The results
      suggest that individuals with schizophrenia tend to have higher functional
      activity in white matter in certain brain regions relative to healthy controls.
      Despite some overlaps, the distinct regions for physiological noise are different
      from those for FA derived from diffusion tensor imaging, and therefore provide a
      unique angle to explore potential mechanisms to white matter abnormality. 

PMID- 25560666
TI  - Substitution effects of a carbonated hydroxyapatite biomaterial against
      intoxication chloride nickel-exposed rats.
AB  - AIMS: This study aimed to investigate the potential effects of a synthetic
      apatite (carbonated hydroxyapatite) on the detoxification of a group of male
      "Wistar" rats exposed to nickel chloride. METHODS: Toxicity was evaluated by
      rats' bioassay of nickel chloride. Wistar rats received this metal daily by
      gavage for seven days (4 mg/ml nickel chloride/200 g body weight, BW). To
      detoxify this organism, a subcutaneous implantation of the apatite is made.
      RESULTS: The results revealed that exposure to nickel induced oxidative stress,
      disorders in the balances of ferric phosphocalcic, renal failures, liver toxicity
      and significant increase in nickel rates in the bones of intoxicated rats. The
      application of the carbonated hydroxyapatite presented in this study restored
      those disorders back to normal. The synthetic apatite protected the rats against
      the toxic effects of nickel by lowering the levels of lipid peroxidation markers
      and improving the activities of defense enzymes. It also amended ferric and
      phosphocalcic equilibriums, protected liver and kidney functions and reduced the
      nickel rate in the bones of the rats. Overall, the results provided strong
      support for the protective role of carbonated hydroxyapatite in the
      detoxification of rats exposed to nickel. Those beneficial effects were further
      confirmed by physico-chemical characterization (X-ray diffraction and infrared
      spectroscopy), which revealed its property of anionic and cationic substitution,
      thus supporting its promising candidacy for future biomedical application.
      CONCLUSION: The hydroxyapatite is an effective biomaterial to solve health
      problems, particularly detoxification against metals (nickel).

PMID- 25560667
TI  - Comparing morphological, chemical and anti-diabetic characteristics of Puerariae
      Lobatae Radix and Puerariae Thomsonii Radix.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Puerariae Lobatae Radix (PLR) and Puerariae
      Thomsonii Radix (PTR) are traditional Chinese medicines used for the treatment of
      diabetes and cardiovascular diseases. These two herbs are used interchangeably in
      clinical practice, even though they possess significantly different chemical
      profiles. In the case of Pueraria species, the misidentification is related to
      the multiple Chinese common names in clinical practice and variable
      pharmaceutical Latin names in different versions of the Pharmacopoeia of the
      People's Republic of China. In addition, there is lack of evidence demonstrating
      how the differences in the chemical profile would impact on the pharmacological
      activity of the two herbs. Therefore, the aim of this study was to compare the
      microscopic, phytochemical profiles and anti-diabetic activity of PLR and PTR so
      that the two species can be differentiated. MATERIALS AND METHODS: The
      microscopic characteristics of the PLR and PTR were observed and measured by an
      optical microscope. The major compounds were quantified by ultra-performance
      liquid chromatography (UPLC) and total flavonoid content (TFC) colorimetric
      assay. The free radical scavenging capacity was assessed by 2,2-diphenyl-2
      picrylhydrazyl (DPPH) antioxidant assays. Anti-diabetic activity was determined
      by the inhibition of porcine pancreatic alpha-amylase and rat intestinal alpha
      glucosidase activities. RESULTS: Microscopic results illustrated that the size of
      xylem vessels (PLR: 0.1390 +/- 0.0184 mm; PTR: 0.0471 +/- 0.0109 mm), number of
      fibre per bundle (PLR: 32.6800 +/- 2.8780; PTR: 16.5900 +/- 0.9982) and the size
      of fibre (PLR: 0.0075 +/- 0.0003 mm(2); PTR: 0.0025 +/- 0.0002 mm(2)) in PLR were
      significantly greater than that in PTR (p<0.01). PLR possessed a significantly
      lower total starch content (PLR: 0.5288 +/- 1.2559 mg starch/g DM; PTR: 76.7954
      +/- 2.9905 mg starch/g DM) and total dietary fibre content (PLR: 4.2886 +/-
      0.3466 g/100g DM; PTR: 12.4148 +/- 0.4541 g/100g DM) as compared to PTR.
      Isoflavonoids including puerarin, daidzin, genistin and daidzein were the major
      chemical constituents in both species. However, the average content of puerarin
      in PLR was found to be eleven times greater than that in PTR. Furthermore, the
      TFC, DPPH free radical scavenging capacity, anti-alpha-amylase and anti-alpha
      glucosidase in the PLR extracts were 4.42, 4.91, 3.10 and 4.22 times greater than
      in the PTR extracts. CONCLUSIONS: This study provides a comprehensive
      investigation on the two medicinal valuable Pueraria species and allows
      differences to be ascertained. This information can be used to update monographs
      which will help practitioners and dispensers differentiate the herbs. Further
      study on the interchangeable use of PLR and PTR in clinical practice is urgently
      warranted.

PMID- 25560668
TI  - In vitro anti-angiogenic effects of Hemidesmus indicus in hypoxic and normoxic
      conditions.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the roots of Hemidesmus indicus
      is widely used in the Indian traditional medicine for many purposes and poly
      herbal preparations containing Hemidesmus are often used by traditional medical
      practitioners for the treatment of cancer. In the context of anticancer
      pharmacology, anti-angiogenic therapy has become an effective strategy for
      inhibiting new vessel formation and contrast tumor growth. These considerations
      are supported by the evidence that most tumors originate in hypoxic conditions
      and limitation of oxygen diffusion stimulates the formation of tumor abnormal
      microvasculature. Aim of this study was to evaluate the in vitro anti-angiogenic
      potential of Hemidesmus indicus (0.31-0.93 mg/mL) on human umbilical vein
      endothelial cells and delineate the main molecular mechanisms involved in its
      anti-angiogenic activity both in normoxia and hypoxia. MATERIALS AND METHODS: The
      decoction of Hemidesmus indicus was subjected to an extensive HPLC phytochemical
      characterization. Its in vitro anti-angiogenic potential was investigated in
      normoxia and hypoxia. Cell proliferation, apoptosis induction, and inhibition of
      endothelial cell migration and invasion were analyzed by flow cytometry. The
      endothelial tube formation assay was evaluated in matrix gel. The capillary tube
      branch points formed were counted using a Motic AE21 microscope and a VisiCam
      videocamera. The regulation of key factors of the neovascularization process such
      as VEGF, HIF-1alpha and VEGFR-2 was explored at mRNA and protein level by real
      time PCR and flow cytometry, respectively. RESULTS: Treatment with Hemidesmus
      resulted in a significant inhibition of cell proliferation and tube formation in
      both normoxia and hypoxia. Hemidesmus differently regulated multiple molecular
      targets related to angiogenesis according to oxygen availability. In normoxia,
      the inhibition of VEGF was the main responsible for its anti-angiogenic effect;
      the angiogenesis inhibition induced in hypoxia was regulated by a more complex
      mechanism involving firstly HIF-1alpha inhibition, and then VEGF and VEGFR-2 down
      regulation. Additionally, the inhibition of endothelial cell migration and
      invasion by Hemidesmus was more pronounced in normoxia than in hypoxia, possibly
      due to the physiological enhanced induction of invasion characteristic of
      hypoxia. CONCLUSIONS: Our results indicate that Hemidesmus might represent a
      promising therapeutic strategy for diseases in which the inhibition of
      angiogenesis could be beneficial, such as cancer. The antiangiogenic activity of
      Hemidesmus is based on multiple interactions with critical steps in the
      angiogenic cascade. VEGF expression stimulated by HIF-1alpha as well as
      endothelial cell migration and differentiation represent important targets of
      Hemidesmus action and might contribute to its cancer therapeutic efficacy that is
      presently emerging and offer a scientific basis for its use in traditional
      medicine.

PMID- 25560669
TI  - The genus Hippocampus--a review on traditional medicinal uses, chemical
      constituents and pharmacological properties.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Several species from the genus Hippocampus have
      been widely used as a traditional medicine or invigorant with long history in
      China. Five species of them have been recorded in Chinese pharmacopoeia with name
      Hippocampus (Chinese name Haima [symbol: see text]). The ethnopharmacologial
      history of this genus indicated that they possess anti-tumor, anti-aging, anti
      fatigue, anti-prostatic hyperplasia activities and can be used for the treatment
      of tumor, aging, fatigue, thrombus, inflammatory, hypertension and impotence.
      This review focuses on the traditional medicinal uses of Hippocampus species, as
      well as the phytochemical, pharmacological and toxicological studies on this
      genus. MATERIALS AND METHODS: To provide an overview of the ethnopharmacology,
      chemical constituents, pharmacology and clinical applications of the genus
      Hippocampus, and to reveal their therapeutic potentials and being an evidence
      base for further research works of the Hippocampus. Information on the
      Hippocampus species was collected from scientific journals, books, thesis and
      reports based on the Chinese herbal classic literature and worldwide accepted
      scientific databases via a library and electronic search (PubMed, Elsevier,
      Scopus, Google Scholar, Springer, Web of Science and CNKI). RESULTS: A survey of
      literature revealed that the major chemical constituents of Hippocampus are
      sterides, essential amino acids, fatty acids and microelements. Experimental
      evidences confirmed that the Hippocampus could be used in treating tumor, aging,
      fatigue, thrombus, inflammatory, hypertension, prostatic hyperplasia and
      impotence. The most important function of Hippocampus in TCM is invigorating
      kidney-yang. The key traditional uses of Hippocampus have been investigated in
      vitro and in vivo, but their mechanism and clinical trial data are needed, and
      the sustainable exploitation of the endangered Hippocampus species should be
      considered. This literature analysis of traditional medicinal uses and
      experimental chemical and pharmacological data of Hippocampus provide a
      scientific basis for future research. CONCLUSIONS: Hippocampus is a promising
      traditional medicine and holds great potential for being exploited as healthy
      products and drugs. Aquaculture and substitutes of Hippocampus are valid
      approaches to protect Hippocampus form being endangered species.

PMID- 25560670
TI  - The natural therapeutic magnesium lithospermate B potently provides
      neuroprotective effects on cerebral ischemia/reperfusion injury in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza, a perennial plant in the
      genus Salvia and popularly known as "Danshen", is highly valued for its roots in
      traditional Chinese medicines (TCMs). It has widely used for the treatment of
      cerebrovascular and cardiovascular diseases in China. Recently, the cerebral
      protection of magnesium lithospermate B (MLB), a working extract from Salvia
      miltiorrhiza, has received more attention. Here, we investigated the therapeutic
      effects of MLB on cerebral ischemia/reperfusion (CI/R) injury using the middle
      cerebral artery occlusion (MCAO) model in rats. MATERIALS AND METHODS: Male
      Sprague-Dawley rats were subjected to CI/R using a thread to occlude the right
      middle cerebral artery. After 2h of cerebral ischemia, the middle cerebral artery
      was reperfused for 24 h. Rats were injected with different doses of MLB (15, 30
      and 60 mg/kg). Infarct zones, neurological deficit scores, brain water content,
      glutamate levels and protein expressions were evaluated after 24h of reperfusion.
      RESULTS: We found that MLB treatment of rats exposed to focal CI/R decreased
      neurological deficit scores, brain water content, glutamate levels and cerebral
      infarct zones. We also demonstrated that MLB can inhibit CI/R injury-induced
      activation of caspase-3, a marker of apoptosis. This protection by MLB against
      CI/R injury was accompanied by an upregulation of p-Akt in the ischemic
      hemisphere. Furthermore, the MLB-induced protection was prevented by treatment
      with a PI3K inhibitor (LY-294002). CONCLUSIONS: The data in the present study
      suggest a potential protective role of MLB against CI/R injury in rats. The
      salient finding of the present study is that this protective effect of MLB is
      likely mediated through an Akt-dependent pathway.

PMID- 25560671
TI  - Optimizing the compatibility of paired-herb in an ancient Chinese herbal
      decoction Kai-Xin-San in activating neurofilament expression in cultured PC12
      cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS), a well-known traditional
      Chinese herbal decoction, has been widely used to treat mental depression and
      memory loss in China. It has a combination of four herbs: Ginseng Radix et
      Rhizoma (GR; root and rhizome of Panax ginseng C. A. Mey.), Polygalae Radix (PR;
      root of Polygala tenuifolia Wild.), Acori Tatarinowii Rhizoma (ATR; rhizome of
      Acorus tatarinowii Schott), and Poria (PO; sclerotium of Poriacocos (Schw.)
      Wolf), from which a pairing of two herbs was considered as paired-herb, such as
      the pairing of GR-PR and ATR-PO. The depression-induced neural cell loss is one
      of the major pathogenesis in depression. Here, an optimized KXS by changing the
      ratio of paired-herbs in KXS was demonstrated aiming at promoting neural cell
      differentiation. MATERIALS AND METHODS: Quantitative assessment of chemical
      markers in each herbal extract was determined by LC-MS. Promoters of
      neurofilaments, NF68 and NF200, linked with luciferase reporter gene (pNF68-Luc
      and pNF200-Luc) were applied in cultured pheochromocytoma (PC12) cells to study
      the transcriptional activation of each herbal extract. The effect of GR-PR and
      ATR-PO in improving NF promoter activity was analyzed by Compusyn software. The
      activation of PKA was indicated. RESULTS: In PC12 cells, an optimized KXS named
      KXS1:5 having 1:5 of GR-PR:ATR-PO had greater capability in promoting the
      expression of neurofilament. The synergistic effect of GR-PR and ATR-PO on the
      improved efficiency was further determined. Moreover, the treatment of H89, a PKA
      inhibitor, significantly inhibited the induced NF promoter activity. CONCLUSION:
      These results indicated an optimized KXS by optimizing the compatibility of
      paired-herb and this compatibility was proven to exert synergistic effect.
      Moreover, the underlying mechanism was mediated by a PKA signaling pathway.

PMID- 25560672
TI  - MRI findings in primary vaginal melanoma-a report of four cases.
AB  - Primary vaginal melanoma is a rare malignant tumor. We review the clinical
      presentation and magnetic resonance imaging (MRI) appearances of this entity in
      four patients. The MRI findings in vaginal melanoma are various and may be
      confused with other malignant vaginal tumor. Pelvic MRI is helpful for accurate
      preoperative staging of vaginal melanoma. 

PMID- 25560673
TI  - Predicting chemically-induced skin reactions. Part II: QSAR models of skin
      permeability and the relationships between skin permeability and skin
      sensitization.
AB  - Skin permeability is widely considered to be mechanistically implicated in
      chemically-induced skin sensitization. Although many chemicals have been
      identified as skin sensitizers, there have been very few reports analyzing the
      relationships between molecular structure and skin permeability of sensitizers
      and non-sensitizers. The goals of this study were to: (i) compile, curate, and
      integrate the largest publicly available dataset of chemicals studied for their
      skin permeability; (ii) develop and rigorously validate QSAR models to predict
      skin permeability; and (iii) explore the complex relationships between skin
      sensitization and skin permeability. Based on the largest publicly available
      dataset compiled in this study, we found no overall correlation between skin
      permeability and skin sensitization. In addition, cross-species correlation
      coefficient between human and rodent permeability data was found to be as low as
      R(2)=0.44. Human skin permeability models based on the random forest method have
      been developed and validated using OECD-compliant QSAR modeling workflow. Their
      external accuracy was high (Q(2)ext=0.73 for 63% of external compounds inside the
      applicability domain). The extended analysis using both experimentally-measured
      and QSAR-imputed data still confirmed the absence of any overall concordance
      between skin permeability and skin sensitization. This observation suggests that
      chemical modifications that affect skin permeability should not be presumed a
      priori to modulate the sensitization potential of chemicals. The models reported
      herein as well as those developed in the companion paper on skin sensitization
      suggest that it may be possible to rationally design compounds with the desired
      high skin permeability but low sensitization potential. 

PMID- 25560676
TI  - Visualisation of quantum evolution in the Stern-Gerlach and Rabi experiments.
AB  - The Stern-Gerlach experiment is a seminal experiment in quantum physics,
      involving the interaction between a particle with spin and an applied magnetic
      field gradient. A recent article [Wennerstrom et al., Phys. Chem. Chem. Phys.,
      2012, 14, 1677-1684] claimed that a full understanding of the Stern-Gerlach
      experiment can only be attained if transverse spin relaxation is taken into
      account, generated by fluctuating magnetic fields originating in the magnetic
      materials which generate the field gradient. This interpretation is contrary to
      the standard quantum description of the Stern-Gerlach experiment, which requires
      no dissipative effects. We present simulations of conventional quantum dynamics
      in the Stern-Gerlach experiment, using extended Wigner functions to describe the
      propagation of the quantum state in space and time. No relaxation effects are
      required to reproduce the qualitative experimental behaviour. We also present
      simulations of quantum dynamics in the Rabi experiment, in which an applied
      radiofrequency field induces spin transitions in the particle wave. 

PMID- 25560675
TI  - Evaluation of the fate and pathological response in the lung and pleura of brake
      dust alone and in combination with added chrysotile compared to crocidolite
      asbestos following short-term inhalation exposure.
AB  - This study was designed to provide an understanding of the biokinetics and
      potential toxicology in the lung and pleura following inhalation of brake dust
      following short term exposure in rats. The deposition, translocation and
      pathological response of brake-dust derived from brake pads manufactured with
      chrysotile were evaluated in comparison to the amphibole, crocidolite asbestos.
      Rats were exposed by inhalation 6h/day for 5 days to either brake-dust obtained
      by sanding of brake-drums manufactured with chrysotile, a mixture of chrysotile
      and the brake-dust or crocidolite asbestos. The chrysotile fibers were relatively
      biosoluble whereas the crocidolite asbestos fibers persisted through the life
      time of the animal. This was reflected in the lung and the pleura where no
      significant pathological response was observed at any time point in the brake
      dust or chrysotile/brake dust exposure groups through 365 days post exposure. In
      contrast, crocidolite asbestos produced a rapid inflammatory response in the lung
      parenchyma and the pleura, inducing a significant increase in fibrotic response
      in both of these compartments. Crocidolite fibers were observed embedded in the
      diaphragm with activated mesothelial cells immediately after cessation of
      exposure. While no chrysotile fibers were found in the mediastinal lymph nodes,
      crocidolite fibers of up to 35 MUm were observed. These results provide support
      that brake-dust derived from chrysotile containing brake drums would not initiate
      a pathological response in the lung or the pleural cavity following short term
      inhalation.

PMID- 25560674
TI  - Predicting chemically-induced skin reactions. Part I: QSAR models of skin
      sensitization and their application to identify potentially hazardous compounds.
AB  - Repetitive exposure to a chemical agent can induce an immune reaction in
      inherently susceptible individuals that leads to skin sensitization. Although
      many chemicals have been reported as skin sensitizers, there have been very few
      rigorously validated QSAR models with defined applicability domains (AD) that
      were developed using a large group of chemically diverse compounds. In this
      study, we have aimed to compile, curate, and integrate the largest publicly
      available dataset related to chemically-induced skin sensitization, use this data
      to generate rigorously validated and QSAR models for skin sensitization, and
      employ these models as a virtual screening tool for identifying putative
      sensitizers among environmental chemicals. We followed best practices for model
      building and validation implemented with our predictive QSAR workflow using
      Random Forest modeling technique in combination with SiRMS and Dragon
      descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating
      sensitizers from non-sensitizers was 71-88% when evaluated on several external
      validation sets, within a broad AD, with positive (for sensitizers) and negative
      (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared
      to the skin sensitization module included in the OECD QSAR Toolbox as well as to
      the skin sensitization model in publicly available VEGA software, our models
      showed a significantly higher prediction accuracy for the same sets of external
      compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and
      CCR. These models were applied to identify putative chemical hazards in the
      Scorecard database of possible skin or sense organ toxicants as primary
      candidates for experimental validation. 

PMID- 25560677
TI  - Efficient and resilient governance of social-ecological systems.
AB  - New institutions are critically needed to improve the resilience of social
      ecological systems globally. Watershed management offers an important model due
      to its ability to govern mixed-ownership landscapes through common property
      regimes, translating national goals into local action. Here, I assess the
      efficacy of state watershed management institutions in the Pacific Northwest,
      based on their ability to support local watershed groups. I use document analysis
      to describe and compare state institutions in Washington, Oregon, Idaho, and
      California. Results indicate that state institutional efficiency and resilience
      are the key factors determining watershed group activity and stability. The
      primary drivers of institutional efficiency and resilience were institutional
      unification, robust funding portfolios, low agency conflict, and strong support
      for economic multiplier effects, creative partnerships, and scholarly research.
      My findings elucidate the critical role of institutional efficiency and
      resilience in governing dynamic and complex social-ecological systems, enabling
      the flexibility to address emergent transformations. 

PMID- 25560678
TI  - Effect of an Olive Oil-Based Lipid Emulsion Compared With a Soybean Oil-Based
      Lipid Emulsion on Liver Chemistry and Bile Acid Composition in Preterm Infants
      Receiving Parenteral Nutrition: A Double-Blind, Randomized Trial.
AB  - BACKGROUND: The pathogenesis of parenteral nutrition (PN)-associated liver
      dysfunction is multifactorial. Lipid emulsions may be one of the putative
      mechanisms. Our aim was to comparatively assess the effect of parenteral olive
      oil- and soybean oil-based lipid emulsions on liver chemistry and bile acid
      composition in preterm infants. METHODS: We performed a double-blind, randomized
      clinical study in which 103 preterm infants were randomly assigned to PN using
      either soybean oil-based lipid emulsion (SO; n = 51) or olive oil (OO)-based
      lipid emulsion (OO; n = 52). The primary end point was liver chemistry. The
      secondary end point was the plasma bile acid composition. RESULTS: One hundred
      infants completed this study. In the SO group, the serum direct bilirubin was
      significantly higher after PN for 7 days compared with the OO group. Bile acids
      increased over time in both treatment groups. However, specific differences in
      the change in bile acid composition over time were noted between groups.
      CONCLUSIONS: Differences in direct bilirubin and bile acid composition were
      observed over time between the 2 groups. Considering the long-term use of lipid
      emulsions in higher risk babies, these findings might be useful for understanding
      the pathogenesis of PN-associated liver dysfunction.

PMID- 25560680
TI  - Fat-Modified Breast Milk Resolves Chylous Pleural Effusion in Infants With
      Postsurgical Chylothorax but Is Associated With Slow Growth.
AB  - BACKGROUND: Chylothorax occurs in ~3%-5% of infants undergoing cardiac surgery.
      Standard treatment requires discontinuation of breast milk feeding, due to the
      abundance of long-chain triglycerides and transition to a medium-chain
      triglyceride (MCT)-based formula. OBJECTIVE: To determine the effectiveness of
      fat-modified breast milk (MBM) for the treatment of chylothorax compared with MCT
      formula. MATERIALS AND METHODS: Infants diagnosed with chylothorax following
      surgery for congenital heart disease between January 2008 and December 2009 at
      The Hospital for Sick Children were eligible for this nonrandomized open-label
      study. Treatment infants (n = 8) received mother's own milk that had been
      modified by removing the fat layer via centrifugation and adding MCT, nutrients,
      and essential fatty acids to provide an estimated 74 kcal/100 mL and 1.4 g/100 mL
      protein (MBM group). Control infants (n = 8) received an MCT formula (MCT group).
      The feeding intervention was a minimum of 6 weeks after chest tube removal per
      The Hospital for Sick Children standard chylothorax treatment protocol. RESULTS:
      Daily volume and duration of chest tube drainage were not different between the
      MBM and MCT groups. While there was no statistically significant difference in
      rates of weight gain (g/d) between feeding groups, infants in the MBM group, who
      tended to be younger, experienced a decline in mean weight (P = .04) and length
      (P = .01) for age z scores. CONCLUSION: Fat-modified breast milk resolved
      chylothorax; however, strategies to address poor growth need to be developed and
      evaluated in larger trials prior to widespread clinical adoption of this novel
      treatment.

PMID- 25560679
TI  - Reversal of Intestinal Failure-Associated Liver Disease by Switching From a
      Combination Lipid Emulsion Containing Fish Oil to Fish Oil Monotherapy.
AB  - Intestinal failure-associated liver disease (IFALD) is a serious complication of
      parenteral nutrition (PN). Studies have shown that the amount and content of
      intravenous lipid emulsions (LEs) used is closely related to the development of
      IFALD. We report 2 cases of IFALD reversed by switching from a combination lipid
      emulsion containing fish oil to fish oil monotherapy (Omegaven; Fresenius Kabi
      Austria Gmbh, Graz, Austria). Patients initially received PN containing SMOFlipid
      20% (SMOF; Fresenius Kabi Austria Gmbh, Graz, Austria), 2.0-3.0 g/kg/d, over 24
      hours. When IFALD developed, LE was switched from SMOF to Omegaven starting at
      1.0 g/kg/d over 12 hours. Case 1 was an 11-month-old girl with a diagnosis of
      extensive Hirschsprung disease up to the proximal jejunum. She developed direct
      bilirubinemia at 3 months, and the patient's LE was switched to Omegaven. A
      decrease in direct bilirubin was observed after 60 days on Omegaven, and IFALD
      was completely resolved after 90 days. Case 2 was a 1-month-old boy with a
      history of gastroschisis diagnosed with megacystis microcolon intestinal
      hypoperistalsis syndrome. He could not tolerate any oral feeds and was kept on
      full PN. He had elevated direct bilirubin and developed IFALD since 5 weeks.
      Omegaven treatment was initiated at 5 months. Direct bilirubin rose to 8 mg/dL
      during the first month on Omegaven. Then a gradual decrease in direct bilirubin
      was observed, and after 5 months on Omegaven, IFALD was completely resolved. In
      conclusion, 2 infants with advanced IFALD showed reversal of cholestasis by
      switching from SMOF to Omegaven monotherapy. 

PMID- 25560681
TI  - Modulation of Dietary Lipid Composition During Acute Respiratory Distress
      Syndrome: Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Pharmaconutrition including omega-3 and competitive analogs of omega
      6 fatty acids has been used to modulate the inflammatory response during acute
      respiratory distress syndrome (ARDS). The clinical benefit of this approach when
      assessed in prospective randomized clinical trials has been inconsistent. We
      tried to assess the reasons for the conflicting results, including the possible
      influence of the composition of the control solution. METHODS: We collected data
      from studies listed in PubMed, Ovid, the Cochrane Database of Systematic Reviews,
      Embase, the U.S. National Institute of Health database, and the ARDSnet database
      up to March 2013. We included all trials that evaluated effects of enteral
      pharmaconutrition vs a control solution on mortality, ventilator-free days,
      length of stay (LOS) in the intensive care unit (ICU), and ICU-free days. A
      sensitivity analysis was carried out to study the influence of the lipid content
      of the control solution. RESULTS: We found 7 eligible studies (802 patients; 405
      randomized to pharmaconutrition). The aggregated results showed no overall effect
      on mortality (risk ratio [RR] = 0.83 [0.55-1.25], P = .37), but there was a
      mortality benefit when only studies in which pharmaconutrition was compared to a
      lipid-rich control solution were considered (RR = 0.57 [0.41-0.78], P < .001).
      ICU LOS was shorter in patients randomized to pharmaconutrition (RR = 0.5 [0.85
      0.16]). CONCLUSION: Use of enteral pharmaconutrition in patients with ARDS was
      associated with decreased mortality only when the comparator solution contained a
      greater amount of lipid than is currently recommended. Hence, there is
      insufficient evidence to support the use of enteral pharmaconutrition in ARDS.

PMID- 25560683
TI  - The 2015 annual review issue.

PMID- 25560682
TI  - Islands as model systems in ecology and evolution: prospects fifty years after
      MacArthur-Wilson.
AB  - The study of islands as model systems has played an important role in the
      development of evolutionary and ecological theory. The 50th anniversary of
      MacArthur and Wilson's (December 1963) article, 'An equilibrium theory of insular
      zoogeography', was a recent milestone for this theme. Since 1963, island systems
      have provided new insights into the formation of ecological communities. Here,
      building on such developments, we highlight prospects for research on islands to
      improve our understanding of the ecology and evolution of communities in general.
      Throughout, we emphasise how attributes of islands combine to provide unusual
      research opportunities, the implications of which stretch far beyond islands.
      Molecular tools and increasing data acquisition now permit re-assessment of some
      fundamental issues that interested MacArthur and Wilson. These include the
      formation of ecological networks, species abundance distributions, and the
      contribution of evolution to community assembly. We also extend our prospects to
      other fields of ecology and evolution - understanding ecosystem functioning,
      speciation and diversification - frequently employing assets of oceanic islands
      in inferring the geographic area within which evolution has occurred, and
      potential barriers to gene flow. Although island-based theory is continually
      being enriched, incorporating non-equilibrium dynamics is identified as a major
      challenge for the future. 

PMID- 25560685
TI  - Effects of the reduction of surgical residents' work hours and implications for
      surgical residency programs: a narrative review.
AB  - BACKGROUND: The widespread implementation of resident work hour restrictions has
      led to significant alterations in surgical training and the postgraduate
      educational experience. We evaluated the experience of surgical residency
      programs as reflected in the literature from 2008 onward in order to summarize
      current challenges and identify key areas in need of further research. METHODS:
      We searched MEDLINE and EMBASE for English-language articles published from
      January 2008 to December 2011 related to work hour restrictions in surgical
      residency programs, including those pertaining to personal well-being, education
      and training, patient care, and faculty experiences. RESULTS: We retrieved 240
      unique abstracts and included 24 studies in the current review. Of the 10 studies
      examining effects on operating room experience, 4 reported negative or mixed
      outcomes and 6 reported neutral outcomes, although non-compliance was
      demonstrated in 2 of these studies. Effects on surgical faculty perceptions were
      consistently reported as negative, while the effect on patient outcomes and
      professionalism were found to be neutral and unchanged. CONCLUSIONS: Further
      studies are needed to characterize operative experience at varying levels of
      training, particularly in the context of strict adherence to new work hours.
      Research that examines the effect of the work hour limitations on professionalism
      and non-operative educational activities, such as reading and simulation-based
      training, as well as sign-over practices, would also be of benefit.

PMID- 25560686
TI  - Directed interactions of block copolypept(o)ides with mannose-binding receptors:
      PeptoMicelles targeted to cells of the innate immune system.
AB  - Core-shell structures based on polypept(o)ides combine stealth-like properties of
      the corona material polysarcosine with adjustable functionalities of the
      polypeptidic core. Mannose-bearing block copolypept(o)ides (PSar-block-PGlu(OBn))
      have been synthesized using 11-amino-3,6,9-trioxa-undecyl-2,3,4,6-tetra-O-acetyl
      O-alpha-D-mannopyranoside as initiator in the sequential ring-opening
      polymerization of alpha-amino acid N-carboxyanhydrides. These amphiphilic block
      copolypept(o)ides self-assemble into multivalent PeptoMicelles and bind to
      mannose-binding receptors as expressed by dendritic cells. Mannosylated micelles
      showed enhanced cell uptake in DC 2.4 cells and in bone marrow-derived dendritic
      cells (BMDCs) and therefore appear to be a suitable platform for immune
      modulation. 

PMID- 25560687
TI  - Morphological changes related to age in mesial root canals of permanent
      mandibular first molars.
AB  - The aim of this study was to evaluate age-related morphological canal changes in
      mesial root canals of mandibular first molars of known ages. Fifty-six specimens
      were selected for this study and distributed into the following four age groups
      (n. 14): a) Group of children under 13 years, b) Group of adolescents (from 14 to
      19 years), c) Group of young adults (from 20 to 39 years) and d) Group of older
      adults (over 40 years). The specimens were in perfect condition because after
      extraction they were carefully cleaned, sterilized, identified and stored in
      water. In order to improve the cleaning, they were placed in 1% sodium
      hypochlorite solution for four hours and rinsed in 10 vol. hydrogen peroxide for
      8 hours. After that, a clearing technique was performed to illustrate root canal
      anatomy. Digitalized images of all samples were obtained by use of a
      stereomicroscope. Canals were noticeably simpler in older adults: they were
      sharply defined and narrow, sometimes too narrow. Calcification nuclei were not
      found and there were only a few remains of internuclear spaces. The canal system
      appeared cleaner, clearer and more sharply defined than in the other age groups.
      It may be concluded that there is a correlation between aging and morphological
      changes in the mesial root canals of mandibular first molars. 

PMID- 25560688
TI  - Microbial diversity in dental unit waterlines.
AB  - Dental health care providers and patients are exposed during ongoing work to
      contamination by the water used in the dental units, due to accidental swallowing
      or aspiration of the sprays generated by the high-speed handpiece and the
      threeway syringe. This study evaluated the quality of water in dental units in
      the public dental care system of Maceio, Alagoas, Brazil, by conducting analyses
      of contamination by total coliforms, E.Coli, heterotrophic bacteria and
      filamentous fungi. We collected 200 mL of water at 5 sites in 6 dental offices of
      the Department of Health located in different parts of the city. A total 212
      isolates and 16 genera of filamentous fungi were identified in the water
      collected from the dental units. Total coliforms indicated that the water used in
      dental units was not appropriate for human consumption. The high levels of
      contamination found in this study showed that water was a potential source of
      cross-infection. 

PMID- 25560689
TI  - Maximum bite force in elderly indigenous and non-indigenous denture wearers.
AB  - The aim of this study was to compare the measures of maximum bite force (MBF) in
      elderly edentulous indigenous (Mapuche) and non-indigenous individuals with new
      complete dentures at two different measuring times. A sample of 100 elderly
      subjects was divided into two groups: 50 indigenous and 50 non-indigenous, each
      including 25 females and 25 males. All individuals were totally edentulous, with
      new maxillary and mandibular removable complete dentures. Measurements were taken
      at the time of new prosthesis placement and after 1 month of use. Subjects were
      asked to perform with maximum effort three bites per side at maximum
      intercuspidation, with a rest time of 2 minutes in between. Statistics were
      analyzed with Student 's t-test. The MBF values were significantly higher in
      indigenous than non-indigenous subjects. Force after 1 month of wearing the new
      prosthesis was significantly higher than at the time of new prosthesis placement.
      No significant difference was found between sides. Elderly indigenous complete
      denture wearers had the greatest MBF values. Denture wearers were observed to
      undergo an adaptation process to the new prosthesis, with MBF increasing
      considerably after one month of use. 

PMID- 25560690
TI  - Gingival response in orthodontic patients: Comparative study between self
      ligating and conventional brackets.
AB  - Orthodontic brackets contribute to the accumulation of bacterial plaque on tooth
      surfaces because they hinder oral hygiene. In contrast to conventional brackets,
      self-ligating brackets do not require additional parts to support the arches,
      thus improving dental hygiene. The aim of this study was to compare the gingival
      response in orthodontic patients wearing self-ligating or conventional brackets.
      A sample of 22 patients aged 16 to 30 years was divided into two groups: Group A,
      treated with selfligating brackets (Damon system) and Group B, treated with
      conventional brackets (Roth technique). The following were assessed during the
      treatment: Plaque Index (PI), Gingival Index (GI) and Probing Depth (PD), and sub
      gingival samples were taken from teeth 14/24 for microbiological observation. No
      statistically significant difference was found between Groups A and B; p>0.05
      (sign-ranked) or between PI, GI and PD at the different times (Friedman's
      Analysis of Variance), even though the indices were found to increase at 14 days,
      particularly for self-ligating brackets. The quantity and quality of
      microorganisms present were compatible with health on days 0, 28 and 56. As from
      day 14 there is a predominance of microbiota compatible with gingivitis in both
      groups. In the samples studied, orthodontic treatment increases bacterial plaque
      and inflammatory gingival response, but gingival-periodontal health can be
      maintained with adequate basic therapy. Self-ligating and conventional brackets
      produced similar gingival response. 

PMID- 25560691
TI  - Association between post-orthodontic treatment gingival margin alterations and
      symphysis dimensions.
AB  - Orthodontic therapy is known to be associated with the development of gingival
      recession. Several factors may be involved in the causal chain of this outcome,
      including anatomical and behavioral aspects. Among the anatomical aspects, the
      dimensions of the mandibular symphysis could play a predisposing role. This study
      evaluated the relationship between the mandibular symphysis dimensions prior to
      orthodontic therapy and the development of gingival recessions on the lower
      incisors and cuspids. Records from 189 orthodontically treated adolescents were
      evaluated, including radiographs, casts and intra-oral photographs. Symphysis
      dimensions were assessed by cephalograms. Gingival margin alterations were
      determined in photographs and cast models. Association between gingival margin
      alterations and symphysis dimensions was tested by chi-square (alpha=0.05).
      Occurrence of gingival recession increased after orthodontic therapy. No
      association was observed on average of symphysis dimensions and the occurrence of
      gingival recessions. It may be concluded that pretreatment symphysis dimensions
      may not be used as predictors of gingival recession after orthodontic therapy. 

PMID- 25560692
TI  - Influence of cantilever length and type of arch antagonist on bone loss in total
      implant-supported prostheses.
AB  - This study selected forty-two implants with full arch implantsupported fixed
      prostheses (with and without a cantilever) with at least five years' loading.
      Radiographic measurements were performed using Digimizer software (MedCalc
      Software, Belgium). Bone loss was measured on the distal side of the implant,
      from the surface of the platform to the edge of the bone crest, and the extent of
      the cantilever was measured from the distal surface of the last abutment to the
      end of the metal structure. Three groups were formed according the length of the
      cantilever: G1: cantilever <= 15 mm; G2: cantilever >15 mm; G3: no cantilever.
      Types of antagonists were grouped as: RP = removable complete denture; FP = fixed
      implant-supported prosthesis; ND = natural dentition. Data were analyzed
      according to the length of the cantilever and type of antagonist using Person's
      test to analyze normality and Student's t-test with P ? 0.05. No statistically
      significant difference was found between G1 and G2; however, increased bone loss
      was observed in both cantilever groups (G1 and G2) compared to G3 (P> 0.05). The
      antagonist showed no significant difference in bone loss ( P ? 0.05). Cantilevers
      showed increases in marginal bone loss. The type of antagonist did not influence
      bone loss. 

PMID- 25560693
TI  - Occurrence of porphyromonas gingivalis and its antibacterial susceptibility to
      metronidazole and tetracycline in patients with chronic periodontitis.
AB  - Chronic periodontitis is a multifactorial infectious disease associated with Gram
      negative strict anaerobes which are immersed in the subgingival biofilm.
      Porphyromonas gingivalis, an important periodontal pathogen, is frequently
      detected in patients with chronic periodontitis. Although isolates of P.
      gingivalis tend to be susceptible to most antimicrobial agents, relatively little
      information is available on its in vitro antimicrobial susceptibility. The aim of
      this study was to determine the frequency of P. gingivalis in patients with
      chronic periodontitis and to assess antimicrobial susceptibility in terms of
      minimum inhibitory concentration (MIC) of clinical isolates to metronidazole and
      tetracycline. A descriptive, observational study was performed including 87
      patients with chronic periodontitis. Samples were taken from the periodontal
      pocket using paper points, which were placed in thioglycollate broth. Samples
      were incubated for 4 hours at 37 degrees C in anaerobic conditions and finally
      replated on Wilkins-Chalgren anaerobic agar (Oxoid). Bacteria were identified
      using the RapIDTMANAII system (Remel) and antimicrobial susceptibility was
      determined with the M.I.C. Evaluator test (MICE, Oxoid). P. gingivalis was
      identified in 30 of the 87 patients with chronic periodontitis, which represents
      a frequency of 34.5%. All 30 isolates (100%) were sensitive to metronidazole,
      with MIC values ranging from 0015-4ug/ml. Regarding tetracycline, 27 isolates
      (90%) were sensitive, with MIC values ranging from <0.015 to 4 ug /ml, the
      remaining three isolates (10%) were resistant to tetracycline with MIC values of
      8ug/ ml. There was no statistically significant difference in age, gender, pocket
      depth, clinical attachment level and severity of periodontitis between the group
      of patients with chronic periodontitis and P. gingivalis and the group of
      patients with chronic periodontitis without P. gingivalis. In conclusion, P.
      gingivalis was found at a frequency of 34.5% in patients with chronic
      periodontitis and clinical isolates were highly sensitive to metronidazole and
      tetracycline. 

PMID- 25560694
TI  - In vitro evaluation of the film thickness of self-etching resin cements.
AB  - The aim of this study was to evaluate the film thickness of selfetching resin
      cement. The following materials were used: Group1, Relyx U100 (3M /ESPE); Group
      2, BisCem (Bisco); Group 3, Max Cem (Kerr); Group 4, Set (SDI) and Group 5, Relyx
      ARC (3M/ESPE) as control. Two 5.4 x 76.2 x 1 mm glass slides were marked in the
      center to identify the area where the material would be placed. A volume of 0.05
      ml was used for each specimen material. After 1, 3 and 6 minutes, a 50 N load was
      applied for one minute. The thickness of each specimen was then measured using a
      digital micrometer to the nearest 1 MUm; (Digimatic, Mitutoyo Corporation,
      Japan.). Data were analyzed using ANOVA and Bonferroni's multiple comparison
      tests. No significant difference was found between the materials tested (p =
      0.0921) or material/time interaction (p = 0.0864), but there were differences in
      the time factor (p = 0.0001). At one minute, the thinnest film was Relyx ARC
      (control) (14 MUm), followed by Relyx U100 (17 MUm), and Maxcem and SeT (19 MUm).
      At 3 minutes, Group 5 (control) was also the thinnest film (19 MUm), followed by
      Group 1 (21 MUm), Group 3 (25 MUm), Group 2 (29 MUm), and Group 4 (31 MUm). At 6
      minutes, Group 4 was the thinnest (34 MUm), followed by Group 1 (38 MUm), Group 5
      (40 MUm), Group 2 (41 MUm) and Group 3 (42 MUm). The film thickness of resin
      cements was influenced by time and polymerization reaction. The film thickness of
      self-etching cements was low. 

PMID- 25560695
TI  - Heat shock protein X purified from Mycobacterium tuberculosis enhances the
      efficacy of dendritic cells-based immunotherapy for the treatment of allergic
      asthma.
AB  - Dendritic cells play an important role in determining whether naive T cells
      mature into either Th1 or Th2 cells. We determined whether heat-shock protein X
      (HspX) purified from Mycobacterium tuberculosis regulates the Th1/Th2 immune
      response in an ovalbumin (OVA)-induced murine model of asthma. HspX increased
      interferon-gamma, IL-17A, -12 and transforming growth factor (TGF)-beta
      production and T-bet gene expression but reduced IL-13 production and GATA-3 gene
      expression. HspX also inhibited asthmatic reactions as demonstrated by an
      increase in the number of eosinophils in bronchoalveolar lavage fluid,
      inflammatory cell infiltration in lung tissues, airway luminal narrowing, and
      airway hyper-responsiveness. Furthermore, HspX enhanced OVA-induced decrease of
      regulatory T cells in the mediastinal lymph nodes. This study provides evidence
      that HspX plays critical roles in the amelioration of asthmatic inflammation in
      mice. These findings provide new insights into the immunotherapeutic role of HspX
      with respect to its effects on a murine model of asthma.

PMID- 25560696
TI  - Network of hypothalamic neurons that control appetite.
AB  - The central nervous system (CNS) controls food intake and energy expenditure via
      tight coordinations between multiple neuronal populations. Specifically, two
      distinct neuronal populations exist in the arcuate nucleus of hypothalamus (ARH):
      the anorexigenic (appetite-suppressing) pro-opiomelanocortin (POMC) neurons and
      the orexigenic (appetite-increasing) neuropeptide Y (NPY)/agouti-related peptide
      (AgRP) neurons. The coordinated regulation of neuronal circuit involving these
      neurons is essential in properly maintaining energy balance, and any disturbance
      therein may result in hyperphagia/obesity or hypophagia/starvation. Thus,
      adequate knowledge of the POMC and NPY/AgRP neuron physiology is mandatory to
      understand the pathophysiology of obesity and related metabolic diseases. This
      review will discuss the history and recent updates on the POMC and NPY/AgRP
      neuronal circuits, as well as the general anorexigenic and orexigenic circuits in
      the CNS.

PMID- 25560697
TI  - Drosophila blood as a model system for stress sensing mechanisms.
AB  - The Drosophila lymph gland is the hematopoietic organ in which stem-like
      progenitors proliferate and give rise to myeloid-type blood cells. Mechanisms
      involved in Drosophila hematopoiesis are well established and known to be
      conserved in the vertebrate system. Recent studies in Drosophila lymph gland have
      provided novel insights into how external and internal stresses integrate into
      blood progenitor maintenance mechanisms and the control of blood cell fate
      decision. In this review, I will introduce a developmental overview of the
      Drosophila hematopoietic system, and recent understandings of how the system uses
      developmental signals not only for hematopoiesis but also as sensors for stress
      and environmental changes to elicit necessary blood responses.

PMID- 25560698
TI  - Antioxidant enzymes as redox-based biomarkers: a brief review.
AB  - The field of redox proteomics focuses to a large extent on analyzing cysteine
      oxidation in proteins under different experimental conditions and states of
      diseases. The identification and localization of oxidized cysteines within the
      cellular milieu is critical for understanding the redox regulation of proteins
      under physiological and pathophysiological conditions, and it will in turn
      provide important information that are potentially useful for the development of
      novel strategies in the treatment and prevention of diseases associated with
      oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes
      are able to serve as redox biomarkers in various human diseases, and they are key
      regulators controlling the redox state of functional proteins. Redox regulators
      with antioxidant properties related to active mediators, cellular organelles, and
      the surrounding environments are all connected within a network and are involved
      in diseases related to redox imbalance including cancer, ischemia/reperfusion
      injury, neurodegenerative diseases, as well as normal aging. In this review, we
      will briefly look at the selected aspects of oxidative thiol modification in
      antioxidant enzymes and thiol oxidation in proteins affected by redox control of
      antioxidant enzymes and their relation to disease.

PMID- 25560700
TI  - Regeneration of the retina: toward stem cell therapy for degenerative retinal
      diseases.
AB  - Degenerative retinal diseases affect millions of people worldwide, which can lead
      to the loss of vision. However, therapeutic approaches that can reverse this
      process are limited. Recent efforts have allowed the possibility of the stem cell
      based regeneration of retinal cells and repair of injured retinal tissues.
      Although the direct differentiation of pluripotent stem cells into terminally
      differentiated photoreceptor cells comprises one approach, a series of studies
      revealed the intrinsic regenerative potential of the retina using endogenous
      retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and
      retinal pigment epithelial cells are candidates for such retinal stem cells that
      can differentiate into multiple types of retinal cells and be integrated into
      injured or developing retina. In this review, we explore our current
      understanding of the cellular identity of these candidate retinal stem cells and
      their therapeutic potential for cell therapy against degenerative retinal
      diseases.

PMID- 25560699
TI  - Technical and clinical aspects of cortisol as a biochemical marker of chronic
      stress.
AB  - Stress is now recognized as a universal premorbid factor associated with many
      risk factors of various chronic diseases. Acute stress may induce an individual's
      adaptive response to environmental demands. However, chronic, excessive stress
      causes cumulative negative impacts on health outcomes through "allostatic load".
      Thus, monitoring the quantified levels of long-term stress mediators would
      provide a timely opportunity for prevention or earlier intervention of stress
      related chronic illnesses. Although either acute or chronic stress could be
      quantified through measurement of changes in physiological parameters such as
      heart rate, blood pressure, and levels of various metabolic hormones, it is still
      elusive to interpret whether the changes in circulating levels of stress
      mediators such as cortisol can reflect the acute, chronic, or diurnal variations.
      Both serum and salivary cortisol levels reveal acute changes at a single point in
      time, but the overall long-term systemic cortisol exposure is difficult to
      evaluate due to circadian variations and its protein-binding capacity. Scalp hair
      has a fairy predictable growth rate of approximately 1 cm/month, and the most 1
      cm segment approximates the last month's cortisol production as the mean value.
      The analysis of cortisol in hair is a highly promising technique for the
      retrospective assessment of chronic stress.

PMID- 25560701
TI  - Therapeutic aptamers: developmental potential as anticancer drugs.
AB  - Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact
      with target molecules through a specific three-dimensional structure, are
      selected from pools of combinatorial oligonucleotide libraries. With their high
      specificity and affinity for target proteins, ease of synthesis and modification,
      and low immunogenicity and toxicity, aptamers are considered to be attractive
      molecules for development as anticancer therapeutics. Two aptamers - one
      targeting nucleolin and a second targeting CXCL12 - are currently undergoing
      clinical trials for treating cancer patients, and many more are under study. In
      this mini-review, we present the current clinical status of aptamers and aptamer
      based cancer therapeutics. We also discuss advantages, limitations, and prospects
      for aptamers as cancer therapeutics.

PMID- 25560702
TI  - Country-of-birth differences in adverse health behaviours among people with type
      2 diabetes.
AB  - OBJECTIVE: To identify differences in patterns of adverse health behaviours among
      people with type 2 diabetes according to country or region of birth. METHODS:
      Population-based study of 23,112 individuals with type 2 diabetes aged 45 years
      and older, from New South Wales, Australia. Self-reported questionnaire data and
      logistic regression models were used to estimate odds ratios for adverse health
      behaviours according to country or region of birth, adjusted for confounding
      factors. RESULTS: People with diabetes born in the Middle East and in the United
      Kingdom (UK) were more likely to be current smokers than those born in
      Australian, while those from Asia were less likely to be smokers. Relative to
      Australian-born people with diabetes, those born in the Middle East were more
      likely to have insufficient physical activity, while those born in Oceania, North
      West Europe and the UK were less likely. People with diabetes from Asia, North
      Africa, the Middle East and Sub-Saharan Africa were less likely to consume
      alcohol than those born in Australia, but people born in the UK were slightly
      more likely to consume alcohol. People with diabetes born in the UK, Asia, and
      North Africa were more likely than those born in Australia to have an inadequate
      intake of fruit and vegetables. CONCLUSION: Adverse health behaviours among
      people with type 2 diabetes varied markedly according to country or region of
      birth. Promoting smoking cessation and increasing physical activity levels among
      people with diabetes who were born in Middle Eastern countries are clear
      priorities.

PMID- 25560703
TI  - Stromal cells and stem cells in clinical bone regeneration.
AB  - Stem-cell-mediated bone repair has been used in clinical trials for the
      regeneration of large craniomaxillofacial defects, to slow the process of bone
      degeneration in patients with osteonecrosis of the femoral head and for
      prophylactic treatment of distal tibial fractures. Successful regenerative
      outcomes in these investigations have provided a solid foundation for wider use
      of stromal cells in skeletal repair therapy. However, employing stromal cells to
      facilitate or enhance bone repair is far from being adopted into clinical
      practice. Scientific, technical, practical and regulatory obstacles prevent the
      widespread therapeutic use of stromal cells. Ironically, one of the major
      challenges lies in the limited understanding of the mechanisms via which
      transplanted cells mediate regeneration. Animal models have been used to provide
      insight, but these models largely fail to reproduce the nuances of human diseases
      and bone defects. Consequently, the development of targeted approaches to
      optimize cell-mediated outcomes is difficult. In this Review, we highlight the
      successes and challenges reported in several clinical trials that involved the
      use of bone-marrow-derived mesenchymal or adipose-tissue-derived stromal cells.
      We identify several obstacles blocking the mainstream use of stromal cells to
      enhance skeletal repair and highlight technological innovations or areas in which
      novel techniques might be particularly fruitful in continuing to advance the
      field of skeletal regenerative medicine. 

PMID- 25560706
TI  - Emerging drugs for acute lung injury.
AB  - INTRODUCTION: Acute respiratory distress syndromes (ARDS) are devastating
      disorders of overwhelming pulmonary inflammation and hypoxemia, resulting in high
      morbidity and mortality. AREAS COVERED: The main pharmacological treatment
      strategies have focused on the attempted inhibition of excessive inflammation or
      the manipulation of the resulting physiological derangement causing respiratory
      failure. Additionally, such interventions may allow reduced occurence mechanical
      ventilation injury. Despite promising preclinical and small clinical studies,
      almost all therapies have been shown to be unsuccessful in large-scale randomized
      controlled trials. The evidence for pharmacological treatment for ARDS is
      reviewed. Potential future treatments are also presented. EXPERT OPINION: We
      suggest for future clinical trials addressing prevention and early intervention
      to attenuate lung injury and progression to respiratory failure.

PMID- 25560704
TI  - Long non-coding RNAs as regulators of the endocrine system.
AB  - Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are
      often lineage-specific and that regulate multiple biological functions. Many are
      nuclear and are essential parts of ribonucleoprotein complexes that modify
      chromatin segments and establish active or repressive chromatin states; others
      are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This
      Review summarizes the current knowledge of lncRNAs as regulators of the endocrine
      system, with a focus on the identification and mode of action of several
      endocrine-important lncRNAs. We highlight lncRNAs that have a role in the
      development and function of pancreatic beta cells, white and brown adipose
      tissue, and other endocrine organs, and discuss the involvement of these
      molecules in endocrine dysfunction (for example, diabetes mellitus). We also
      address the associations of lncRNAs with nuclear receptors involved in major
      hormonal signalling pathways, such as estrogen and androgen receptors, and the
      relevance of these associations in certain endocrine cancers.

PMID- 25560707
TI  - Differential metabolomic analysis of the potential antiproliferative mechanism of
      olive leaf extract on the JIMT-1 breast cancer cell line.
AB  - A new differential metabolomic approach has been developed to identify the
      phenolic cellular metabolites derived from breast cancer cells treated with a
      supercritical fluid extracted (SFE) olive leaf extract. The SFE extract was
      previously shown to have significant antiproliferative activity relative to
      several other olive leaf extracts examined in the same model. Upon SFE extract
      incubation of JIMT-1 human breast cancer cells, major metabolites were identified
      by using HPLC coupled to electrospray ionization quadrupole-time-of-flight mass
      spectrometry (ESI-Q-TOF-MS). After treatment, diosmetin was the most abundant
      intracellular metabolite, and it was accompanied by minor quantities of apigenin
      and luteolin. To identify the putative antiproliferative mechanism, the major
      metabolites and the complete extract were assayed for cell cycle, MAPK and PI3K
      proliferation pathways modulation. Incubation with only luteolin showed a
      significant effect in cell survival. Luteolin induced apoptosis, whereas the
      whole olive leaf extract incubation led to a significant cell cycle arrest at the
      G1 phase. The antiproliferative activity of both pure luteolin and olive leaf
      extract was mediated by the inactivation of the MAPK-proliferation pathway at the
      extracellular signal-related kinase (ERK1/2). However, the flavone concentration
      of the olive leaf extract did not fully explain the strong antiproliferative
      activity of the extract. Therefore, the effects of other compounds in the
      extract, probably at the membrane level, must be considered. The potential
      synergistic effects of the extract also deserve further attention. Our
      differential metabolomics approach identified the putative intracellular
      metabolites from a botanical extract that have antiproliferative effects, and
      this metabolomics approach can be expanded to other herbal extracts or
      pharmacological complex mixtures. 

PMID- 25560705
TI  - TSH-receptor-expressing fibrocytes and thyroid-associated ophthalmopathy.
AB  - Thyroid-associated ophthalmopathy (TAO) is a vexing and undertreated ocular
      component of Graves disease in which orbital tissues undergo extensive
      remodelling. My colleagues and I have introduced the concept that fibrocytes
      expressing the haematopoietic cell antigen CD34 (CD34(+) fibrocytes), which are
      precursor cells of bone-marrow-derived monocyte lineage, express the TSH receptor
      (TSHR). These cells also produce several other proteins whose expression was
      traditionally thought to be restricted to the thyroid gland. TSHR-expressing
      fibrocytes in which the receptor is activated by its ligand generate extremely
      high levels of several inflammatory cytokines. Acting in concert with TSHR, the
      insulin-like growth factor 1 receptor (IGF-1R) expressed by orbital fibroblasts
      and fibrocytes seems to be necessary for TSHR-dependent cytokine production, as
      anti-IGF-1R blocking antibodies attenuate these proinflammatory actions of TSH.
      Furthermore, circulating fibrocytes are highly abundant in patients with TAO and
      seem to infiltrate orbital connective tissues, where they might transition to
      CD34(+) fibroblasts. My research group has postulated that the infiltration of
      fibrocytes into the orbit, their unique biosynthetic repertoire and their
      proinflammatory and profibrotic phenotype account for the characteristic
      properties exhibited by orbital connective tissues that underlie susceptibility
      to TAO. These insights, which have emerged in the past few years, might be of use
      in therapeutically targeting pathogenic orbit-infiltrating fibrocytes selectively
      by utilizing novel biologic agents that interfere with TSHR and IGF-1R
      signalling.

PMID- 25560708
TI  - ASO titer or not? When to use streptococcal serology: a guide for clinicians.
AB  - Clinicians frequently request serologic tests to provide evidence of prior
      infection by Streptococcus pyogenes, especially when suspecting a diagnosis of
      acute rheumatic fever or post-streptococcal glomerulonephritis. However, the
      interpretation of these tests is difficult and should take account of the
      clinical features, epidemiological setting, and pre-test probability, as well as
      the specific aspects of the assay. This review details the characteristics of
      streptococcal serologic assays and provides recommendations for their use and
      interpretation. 

PMID- 25560710
TI  - Efficient calculation of exact probability distributions of integer features on
      RNA secondary structures.
AB  - BACKGROUND: Although the needs for analyses of secondary structures of RNAs are
      increasing, prediction of the secondary structures of RNAs are not always
      reliable. Because an RNA may have a complicated energy landscape, comprehensive
      representations of the whole ensemble of the secondary structures, such as the
      probability distributions of various features of RNA secondary structures are
      required. RESULTS: A general method to efficiently compute the distribution of
      any integer scalar/vector function on the secondary structure is proposed. We
      also show two concrete algorithms, for Hamming distance from a reference
      structure and for 5'-3' distance, which can be constructed by following our
      general method. These practical applications of this method show the
      effectiveness of the proposed method. CONCLUSIONS: The proposed method provides a
      clear and comprehensive procedure to construct algorithms for distributions of
      various integer features. In addition, distributions of integer vectors, that is
      a combination of different integer scores, can be also described by applying our
      2D expanding technique.

PMID- 25560709
TI  - General and advanced diagnostic tools to detect Mycobacterium tuberculosis and
      their drug susceptibility: a review.
AB  - The global control of tuberculosis remains a great challenge from the standpoint
      of diagnosis, detection of drug resistance, and treatment, because treatment can
      only be initiated when infection is detected, and is guided by the results of
      antimicrobial susceptibility testing. To a large extent, non-molecular,
      immunological, and other biochemical methods are refinements or modifications of
      conventional methods, with the primary goal of providing more rapid test results.
      In contrast, molecular methods use novel technologies to detect the presence of
      Mycobacterium tuberculosis complex and genes conferring drug resistance. As a
      group, molecular technologies offer the greatest potential for laboratories in
      resource-rich countries because they have the highest sensitivity and
      specificity. In resource-poor settings, continued development of affordable,
      sensitive, and specific diagnostic tools will be required, where the incidence of
      disease is highest. 

PMID- 25560711
TI  - Valganciclovir for the prevention of complications of late cytomegalovirus
      infection after allogeneic hematopoietic cell transplantation: a randomized
      trial.
AB  - BACKGROUND: Optimal prevention of late cytomegalovirus (CMV) disease is poorly
      defined. OBJECTIVE: To compare valganciclovir prophylaxis with polymerase chain
      reaction-guided preemptive therapy. DESIGN: Randomized, double-blind trial.
      (ClinicalTrials.gov: NCT00016068). SETTING: Multicenter trial. PATIENTS: 184
      recipients of hematopoietic cell transplantation (HCT) who were at high risk for
      late CMV disease (95 patients received valganciclovir and 89 received placebo).
      INTERVENTION: 6 months of valganciclovir (900 mg/d) or placebo. Patients with
      polymerase chain reaction positivity at 1000 copies/mL or greater or a 5-fold
      increase over baseline were treated with ganciclovir or valganciclovir (5 mg/kg
      or 900 mg twice daily, respectively). MEASUREMENTS: The composite primary end
      point was death, CMV disease, or other invasive infections by 270 days after HCT.
      Secondary end points were CMV disease, CMV DNAemia, death, other infections,
      resource utilization, ganciclovir resistance, quality of life, immune
      reconstitution, and safety. RESULTS: The primary composite outcome occurred in
      20% of valganciclovir recipients versus 21% of placebo-preemptive therapy
      recipients (treatment difference, -0.01 [95% CI, -0.13 to 0.10]; P = 0.86). There
      was no difference in the primary end point or its components 640 days after HCT.
      The incidence of a CMV DNAemia level of 1000 copies/mL or greater or a 5-fold
      increase over baseline was reduced in the valganciclovir group (11% vs. 36%; P <
      0.001). Neutropenia was not significantly different at the absolute neutrophil
      count of less than 0.5 * 109 cells/L (P = 0.57); however, more patients received
      hematopoietic growth factors in the valganciclovir group (25.3% vs. 12.4%; P =
      0.026). No significant differences were seen in other secondary outcomes.
      LIMITATION: Some high-risk patients were not included. CONCLUSION: Valganciclovir
      prophylaxis was not superior in reducing the composite end point of CMV disease,
      invasive bacterial or fungal disease, or death when compared with polymerase
      chain reaction-guided preemptive therapy. Both strategies performed similarly
      with regard to most clinical outcomes. PRIMARY FUNDING SOURCE: Roche
      Laboratories.

PMID- 25560712
TI  - D-dimer testing to select patients with a first unprovoked venous thromboembolism
      who can stop anticoagulant therapy: a cohort study.
AB  - BACKGROUND: Normal D-dimer levels after withdrawal of anticoagulant therapy are
      associated with a reduced risk for recurrence in patients with unprovoked venous
      thromboembolism (VTE) and may justify stopping treatment. OBJECTIVE: To determine
      whether patients with a first unprovoked VTE and negative D-dimer test result who
      stop anticoagulant therapy have a low risk for recurrence. DESIGN: Prospective
      management study with blinded outcome assessment. (ClinicalTrials.gov:
      NCT00720915). SETTING: 13 university-affiliated clinical centers. PATIENTS: 410
      adults aged 75 years or younger with a first unprovoked proximal deep venous
      thrombosis or pulmonary embolism who had completed 3 to 7 months of anticoagulant
      therapy. INTERVENTION: Anticoagulant therapy was stopped if D-dimer test results
      were negative and was not restarted if results were still negative after 1 month.
      MEASUREMENTS: Recurrent VTE during an average follow-up of 2.2 years. RESULTS: In
      319 patients (78%) who had 2 negative D-dimer results and did not restart
      anticoagulant therapy, rates of recurrent VTE were 6.7% (95% CI, 4.8% to 9.0%)
      per patient-year overall (42 of 319), 9.7% (CI, 6.7% to 13.7%) per patient-year
      in men (33 of 180), 5.4% (CI, 2.5% to 10.2%) per patient-year in women with VTE
      not associated with estrogen therapy (9 of 81), and 0.0% (CI, 0.0% to 3.0%) per
      patient-year in women with VTE associated with estrogen therapy (0 of 58) (P =
      0.001 for the 3-group comparison). LIMITATIONS: Imprecision in female subgroups.
      Results may not be generalizable to different D-dimer assays from the one used in
      the study. CONCLUSION: The risk for recurrence in patients with a first
      unprovoked VTE who have negative D-dimer results is not low enough to justify
      stopping anticoagulant therapy in men but may be low enough to justify stopping
      therapy in women. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

PMID- 25560714
TI  - Transparent Reporting of a multivariable prediction model for Individual
      Prognosis or Diagnosis (TRIPOD): the TRIPOD statement.
AB  - Prediction models are developed to aid health care providers in estimating the
      probability or risk that a specific disease or condition is present (diagnostic
      models) or that a specific event will occur in the future (prognostic models), to
      inform their decision making. However, the overwhelming evidence shows that the
      quality of reporting of prediction model studies is poor. Only with full and
      clear reporting of information on all aspects of a prediction model can risk of
      bias and potential usefulness of prediction models be adequately assessed. The
      Transparent Reporting of a multivariable prediction model for Individual
      Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for
      the reporting of studies developing, validating, or updating a prediction model,
      whether for diagnostic or prognostic purposes. This article describes how the
      TRIPOD Statement was developed. An extensive list of items based on a review of
      the literature was created, which was reduced after a Web-based survey and
      revised during a 3-day meeting in June 2011 with methodologists, health care
      professionals, and journal editors. The list was refined during several meetings
      of the steering group and in e-mail discussions with the wider group of TRIPOD
      contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed
      essential for transparent reporting of a prediction model study. The TRIPOD
      Statement aims to improve the transparency of the reporting of a prediction model
      study regardless of the study methods used. The TRIPOD Statement is best used in
      conjunction with the TRIPOD explanation and elaboration document. To aid the
      editorial process and readers of prediction model studies, it is recommended that
      authors include a completed checklist in their submission (also available at
      www.tripod-statement.org). 

PMID- 25560713
TI  - Comparative effectiveness of pharmacologic interventions for knee osteoarthritis:
      a systematic review and network meta-analysis.
AB  - BACKGROUND: The relative efficacy of available treatments of knee osteoarthritis
      (OA) must be determined for rational treatment algorithms to be formulated.
      PURPOSE: To examine the efficacy of treatments of primary knee OA using a network
      meta-analysis design, which estimates relative effects of all treatments against
      each other. DATA SOURCES: MEDLINE, EMBASE, Web of Science, Google Scholar,
      Cochrane Central Register of Controlled Trials from inception through 15 August
      2014, and unpublished data. STUDY SELECTION: Randomized trials of adults with
      knee OA comparing 2 or more of the following: acetaminophen, diclofenac,
      ibuprofen, naproxen, celecoxib, intra-articular (IA) corticosteroids, IA
      hyaluronic acid, oral placebo, and IA placebo. DATA EXTRACTION: Two reviewers
      independently abstracted study data and assessed study quality. Standardized mean
      differences were calculated for pain, function, and stiffness at 3-month follow
      up. DATA SYNTHESIS: Network meta-analysis was performed using a Bayesian random
      effects model; 137 studies comprising 33,243 participants were identified. For
      pain, all interventions significantly outperformed oral placebo, with effect
      sizes from 0.63 (95% credible interval [CrI], 0.39 to 0.88) for the most
      efficacious treatment (hyaluronic acid) to 0.18 (CrI, 0.04 to 0.33) for the least
      efficacious treatment (acetaminophen). For function, all interventions except IA
      corticosteroids were significantly superior to oral placebo. For stiffness, most
      of the treatments did not significantly differ from one another. LIMITATION: Lack
      of long-term data, inadequate reporting of safety data, possible publication
      bias, and few head-to-head comparisons. CONCLUSION: This method allowed
      comparison of common treatments of knee OA according to their relative efficacy.
      Intra-articular treatments were superior to nonsteroidal anti-inflammatory drugs,
      possibly because of the integrated IA placebo effect. Small but robust
      differences were observed between active treatments. All treatments except
      acetaminophen showed clinically significant improvement from baseline pain. This
      information, along with the safety profiles and relative costs of included
      treatments, will be helpful for individualized patient care decisions. PRIMARY
      FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID- 25560715
TI  - Celebrating the ACP centennial: from the Annals archive.

PMID- 25560716
TI  - Relative efficacy of knee osteoarthritis treatments: are all placebos created
      equal?

PMID- 25560717
TI  - TRIPOD: a new reporting baseline for developing and interpreting prediction
      models.

PMID- 25560718
TI  - The American Board of Internal Medicine.

PMID- 25560719
TI  - The American Board of Internal Medicine.

PMID- 25560720
TI  - The American Board of Internal Medicine.

PMID- 25560721
TI  - The American Board of Internal Medicine.

PMID- 25560722
TI  - Maintenance of certification.

PMID- 25560723
TI  - Maintenance of certification.

PMID- 25560724
TI  - Maintenance of certification.

PMID- 25560725
TI  - Maintenance of certification.

PMID- 25560726
TI  - Maintenance of certification.

PMID- 25560727
TI  - Maintenance of certification.

PMID- 25560728
TI  - Maintenance of certification.

PMID- 25560729
TI  - In the clinic. Rotator cuff disease.
AB  - Shoulder pain is a common musculoskeletal disorder and has a substantial negative
      effect on quality of life. Its monthly prevalence in the general population is
      reported to be between 18% and 31%, whereas lifetime prevalence ranges between
      6.7% and 66.7%. Shoulder pain is the third most frequent musculoskeletal reason
      to present to primary care and accounts for up to 10% of all referrals to
      physical therapists. Although the natural history of shoulder pain varies and is
      often self-limiting,up to half of persons who present for care, particularly the
      elderly, might continue to have pain and/or functional disturbance for up to 2
      years after presentation.

PMID- 25560730
TI  - Transparent Reporting of a multivariable prediction model for Individual
      Prognosis or Diagnosis (TRIPOD): explanation and elaboration.
AB  - The TRIPOD (Transparent Reporting of a multivariable prediction model for
      Individual Prognosis Or Diagnosis) Statement includes a 22-item checklist, which
      aims to improve the reporting of studies developing, validating, or updating a
      prediction model, whether for diagnostic or prognostic purposes. The TRIPOD
      Statement aims to improve the transparency of the reporting of a prediction model
      study regardless of the study methods used. This explanation and elaboration
      document describes the rationale; clarifies the meaning of each item; and
      discusses why transparent reporting is important, with a view to assessing risk
      of bias and clinical usefulness of the prediction model. Each checklist item of
      the TRIPOD Statement is explained in detail and accompanied by published examples
      of good reporting. The document also provides a valuable reference of issues to
      consider when designing, conducting, and analyzing prediction model studies. To
      aid the editorial process and help peer reviewers and, ultimately, readers and
      systematic reviewers of prediction model studies, it is recommended that authors
      include a completed checklist in their submission. The TRIPOD checklist can also
      be downloaded from www.tripod-statement.org. 

PMID- 25560731
TI  - Risk analysis, diagnosis and management of gastrointestinal mucositis in
      pediatric cancer patients.
AB  - Mucositis is a complex inflammatory reaction of the mucous membranes of the
      alimentary tract upon chemotherapy and radiotherapy treatment in oncology
      patients. Mucositis can be subdivided in oral and gastrointestinal mucositis (GI
      mucositis). The damage to the gastrointestinal tract compromises the intestinal
      function and thereby the nutritional status and the quality of life, and
      eventually affects survival. The literature on GI mucositis focuses mainly on
      adults. This review focuses on data available on GI mucositis in pediatric cancer
      patients. An evaluation of the clinical presentation and consequences of GI
      mucositis in children is outlined. The review summarizes key issues for
      clinicians with respect to risk analysis for developing mucositis and the
      diagnosis of this condition in children. Information on these issues is obtained
      from clinical trials in children and adults, and from animal models. Diagnostic
      tools and assessment of severity of GI mucositis in children is elaborated on.
      Furthermore, the clinical management of the symptoms and consequences of GI
      mucositis in children, with specific focus on nutritional support, are discussed.

PMID- 25560733
TI  - Eslicarbazepine acetate for a patient with highly resistant epicrania fugax.

PMID- 25560732
TI  - Targeting vascular endothelial growth factor (VEGF) pathway in iodine-refractory
      differentiated thyroid carcinoma (DTC): from bench to bedside.
AB  - Thyroid cancer is the most common endocrine malignancy, representing 1% of all
      human malignancies; its incidence has been escalating worldwide during the last
      decades. In recent years important molecular pathways contributing to tumor
      progression and worse survival rates have been identified in iodine-refractory
      differentiated thyroid carcinoma (DTC) with the consequent development of
      molecular therapeutics to target these specific oncogenic pathways. For example,
      a positive correlation has been found between expression of vascular endothelial
      growth factor (VEGF) and a more aggressive phenotype of DTC. This has led to the
      widespread adoption of VEGF-targeted therapeutics in the preclinical and clinical
      settings. In this review we will provide an overview of the different aspects of
      the use of VEGF-pathway-oriented treatments in iodine-refractory DTC with
      particular focus on future prospects. 

PMID- 25560735
TI  - Mitral valve geometry in paediatric rheumatic mitral regurgitation.
AB  - Rheumatic mitral valve disease is associated with valvulitis and valvular
      regurgitation; however, the effect of the rheumatic process on the mitral valve
      geometry and function is not well understood. To assess mitral valve annulus
      remodelling in rheumatic mitral valve disease, 16 subjects aged 6-15 years with
      rheumatic mitral valve regurgitation [MR] [6 mild or moderate (Group 1), 10
      severe (Group 2)] and 7 age- and body size-matched normal controls with adequate
      trans-thoracic echocardiograms were recruited. None of the patients had undergone
      surgical intervention and none had more than mild aortic regurgitation. None of
      the patients had mitral stenosis. 3D mitral valve geometry was assessed using a
      Tomtec system. The non-planar angle was increased in all subjects during early
      (control 147 degrees  +/- 10, Group 1 168 degrees  +/- 9, Group 2 166 degrees  +/
      10; p < 0.05) and late systole (control 149 degrees  +/- 12, Group 1 162 degrees
      +/- 10, Group 2 164 degrees  +/- 6; p < 0.05), indicating loss of saddle shape.
      2D annular area increased in Group 2 (control 397 +/- 48 mm(2)/m(2) vs Group 2
      739 +/- 207, p < 0.05) with no significant change in annular perimeter indicating
      leaflet effacement. Mitral valve area correlated with left ventricular size (p <
      0.001, r (2) = 0.74). There was no significant change in valve area and perimeter
      between early and late systole. Remodelling of the mitral valve apparatus in
      childhood rheumatic heart disease results in abnormal annular geometry. The
      mitral valve loses its saddle shape regardless of the severity of MR. This may be
      a consequence of inflammation on the fibrous trigones and surrounding annulus. In
      contrast, annular area enlargement occurs as a result of leaflet effacement and
      relates to MR severity and LV size.

PMID- 25560734
TI  - MicroRNA-574-3p, identified by microRNA library-based functional screening,
      modulates tamoxifen response in breast cancer.
AB  - Most primary breast cancers express estrogen receptor alpha and can be treated
      via endocrine therapy using anti-estrogens such as tamoxifen; however, acquired
      endocrine resistance is a critical issue. To identify tamoxifen response-related
      microRNAs (miRNAs) in breast cancer, MCF-7 cells infected with a lentiviral miRNA
      library were treated with 4-hydroxytamoxifen (OHT) or vehicle for 4 weeks, and
      the amounts of individual miRNA precursors that had integrated into the genome
      were evaluated by microarray. Compared to the vehicle-treated cells, 5 'dropout'
      miRNAs, which were downregulated in OHT-treated cells, and 6 'retained' miRNAs,
      which were upregulated in OHT-treated cells, were identified. Of the dropout
      miRNAs, we found that miR-574-3p expression was downregulated in clinical breast
      cancer tissues as compared with their paired adjacent tissues. In addition, anti
      miR-574-3p reversed tamoxifen-mediated suppression of MCF-7 cell growth. Clathrin
      heavy chain (CLTC) was identified as a miR-574-3p target gene by in silico
      algorithms and luciferase reporter assay using the 3' untranslated region of CLTC
      mRNA. Interestingly, loss and gain of miR-574-3p function in MCF-7 cells causes
      CLTC to be upregulated and downregulated, respectively. These results suggest
      that functional screening mediated by miRNA libraries can provide new insights
      into the genes essential for tamoxifen response in breast cancer. 

PMID- 25560737
TI  - Pancreatic metastases from renal cell carcinoma treated with stereotactic body
      radiation therapy.

PMID- 25560736
TI  - Catheter-based interventions for modified Blalock-Taussig shunt obstruction: a 20
      year experience.
AB  - Thrombotic occlusion of a modified Blalock-Taussig (BT) shunt is rare, leading to
      life-threatening hypoxemia. Rescue percutaneous interventions may allow
      recanalization of the systemic-to-pulmonary shunt but data on large patients'
      scales are lacking. We aimed to describe safety and effectiveness of catheter
      based interventions to restore modified BT shunt patency. All patients who
      attempted transcatheter intervention for thrombotic occlusion of a modified BT
      shunt at our Institution from 1994 to 2014 were reviewed. Characteristics,
      management, and outcomes of the 28 identified patients were analyzed. Thirty
      three procedures were performed at a median age of 0.6 years old (range 0.03-32.1
      years) and a median weight of 5.8 kg (range 2.2-82 kg). Percutaneous intervention
      consisted in 33 balloon angioplasty (100 %) and 14 stent implantations (42.4 %).
      Thrombolytic agents were also used in 6.1 % cases. No peri-procedural death
      occurred but complications were observed in five patients (15.2 %), including one
      catheter-induced transient complete atrioventricular block, one cardiac
      tamponade, and one massive thrombo-embolic stroke. Early procedural success was
      obtained in 28 patients (84.8 %) and remained long-lasting in 26 patients (78.8
      %). A young age and a low body-weight at the time of the procedure were
      significantly associated with procedural failure (p = 0.0364 and p = 0.0247,
      respectively). Although technically challenging and carrying potential major
      complications, transcatheter intervention can be considered as an efficient
      rescue strategy to restore patency in case of thrombotic obstruction of a
      modified BT shunt.

PMID- 25560738
TI  - Isolation, structure elucidation, and total synthesis of tryptopeptins A and B,
      new TGF-beta signaling modulators from Streptomyces sp.
AB  - Two new microbial metabolites, tryptopeptins A (1) and B (2), were isolated from
      the cultured broth of Streptomyces sp. KUSC-G11, as modulators of the
      transforming growth factor-beta (TGF-beta) signaling pathway. Their chemical
      structures consisting of isovalerate, N-Me-L-Val, L-allo-Thr, and a tryptophan
      related residue were elucidated on the basis of spectroscopic analyses, while
      they were unambiguously determined by total syntheses. A structure-activity
      relationship (SAR) study using natural and synthesized tryptopeptins revealed the
      importance of the alpha,beta-epoxyketone function located at the C terminus.
      These new TGF-beta signaling modulators would be highly useful for development of
      new drug leads targeting TGF-beta-related diseases such as fibrosis and cancer.

PMID- 25560739
TI  - Response of a phytoplanktonic assemblage to copper and zinc enrichment in
      microcosm.
AB  - The response of a laboratory-raised phytoplankton assemblage to copper and zinc
      enrichment was studied. Higher intracellular accumulation of both the test metals
      caused disappearance of metal sensitive species, loss of diversity and species
      richness, reduced growth rate, Chl a and biovolume; however, the community could
      recover after 14 days of incubation. Cyanobacteria showed marked sensitivity to
      both the test metals besides some diatoms, such as, Cyclotella meneghiniana and
      Melosira granulata. Metal enrichment enhanced the relative abundance of species
      like Scenedesmus quadricauda, Oocystis borgei, Achnanthes exigua, Fragilaria
      capucina and Nitzschia amphibia, and these were apparently metal tolerant. Cu and
      Zn stress induces formation of lipid bodies (bigger in size as well as in number)
      and morphological abnormalities in diatoms. Among these two metals, Cu impact was
      higher than Zn despite the fact that the intracellular accumulation of Zn was
      higher than Cu. Deformed raphe and mixed deformities in diatoms were exclusively
      found under heavy metal stress which was well supported by regression analysis.
      Finally the present study gives new insight for using diatoms as an effective
      tool for biomonitoring and biofuel production. 

PMID- 25560740
TI  - Determining the sensitivity of the Antarctic amphipod Orchomenella pinguides to
      metals using a joint model of survival response to exposure concentration and
      duration.
AB  - Developing water quality guidelines for Antarctic marine environments requires
      understanding the sensitivity of local biota to contaminant exposure. Antarctic
      invertebrates have shown slower contaminant responses in previous experiments
      compared to temperate and tropical species in standard toxicity tests.
      Consequently, test methods which take into account environmental conditions and
      biological characteristics of cold climate species need to be developed. This
      study investigated the effects of five metals on the survival of a common
      Antarctic amphipod, Orchomenella pinguides. Multiple observations assessing
      mortality to metal exposure were made over the 30 days exposure period.
      Traditional toxicity tests with quantal data sets are analysed using methods such
      as maximum likelihood regression (probit analysis) and Spearman-Karber which
      treat individual time period endpoints independently. A new statistical model was
      developed to integrate the time-series concentration-response data obtained in
      this study. Grouped survival data were modelled using a generalized additive
      mixed model (GAMM) which incorporates all the data obtained from multiple
      observation times to derive time integrated point estimates. The sensitivity of
      the amphipod, O. pinguides, to metals increased with increasing exposure time.
      Response times varied for different metals with amphipods responding faster to
      copper than to cadmium, lead or zinc. As indicated by 30 days lethal
      concentration (LC50) estimates, copper was the most toxic metal (31 ug/L),
      followed by cadmium (168 ug/L), lead (256 ug/L) and zinc (822 ug/L). Nickel
      exposure (up to 1.12 mg/L) did not affect amphipod survival. Using longer
      exposure durations and utilising the GAMM model provides an improved methodology
      for assessing sensitivities of slow responding Antarctic marine invertebrates to
      contaminants. 

PMID- 25560741
TI  - Molecular analysis of red maple (Acer rubrum) populations from a reclaimed mining
      region in Northern Ontario (Canada): soil metal accumulation and translocation in
      plants.
AB  - Red maple (Acer rubrum) species is one of the most widespread deciduous
      (hardwood) trees of eastern North America. It is among the dominant tree species
      in the Northern Ontario after land reclamation. To date, the effects of heavy
      metal contamination from the mining activities on terrestrial ecosystems are not
      well understood. The main objectives of the present study are (1) to determine
      the level of phytoavailable metal in soil and accumulation in A. rubrum, and (2)
      to compare the levels of genetic variation among and within A. rubrum populations
      from areas with different metal contents in a Northern Ontario region. The total
      heavy metal levels were found to be high but the availability of these metals
      were much lower. We found that red maple does not accumulate heavy metals in
      their leaves as other hardwood species. The translocation factors were 0.05,
      0.21, 0.38, 0.90, and 2.8 for Cu, Ni, Fe, Zn, and Mg, respectively. The levels of
      genetic variation in red maple populations from reclaimed lands in Northern
      Ontario were moderate to high since the percentage of polymorphic loci varied
      between 51 and 67%. The mean values for observed number of alleles (Na),
      effective number of alleles (Ne), Nei's gene diversity (h), and Shannon's
      information index (I) were 1.60, 1.24, 0.15 and 0.24, respectively. The
      population differentiation (GST) among the fragmented populations was high (0.28)
      despite a high level of gene flow (Nm = 1.28). Nevertheless, all the populations
      within the targeted region were genetically closely related. A specific ISSR
      marker that was identified in all the samples from the reference sites was absent
      in most samples from metal contaminated. This specific band was cloned and
      sequenced. Overall, the present study confirms that red maple populations in
      Northern Ontario are genetically sustainable despite the high level of total
      metal content in soil.

PMID- 25560742
TI  - Predictors of initial weight loss among women with abdominal obesity: a path
      model using self-efficacy and health-promoting behaviour.
AB  - AIM: To identify predictors of initial weight loss among women with abdominal
      obesity by using a path model. BACKGROUND: Successful weight loss in the initial
      stages of long-term weight management may promote weight loss maintenance.
      DESIGN: A longitudinal study design. METHODS: Study participants were 75 women
      with abdominal obesity, who were enrolled in a 12-month Community-based Heart and
      Weight Management Trial and followed until a 6-month assessment. The Weight
      Efficacy Lifestyle, Exercise Self-Efficacy and Health Promoting Lifestyle Profile
      II measured diet self-efficacy, exercise self-efficacy and health-promoting
      behaviour respectively. All endogenous and exogenous variables used in our path
      model were change variables from baseline to 6 months. Data were collected
      between May 2011-May 2012. FINDINGS: Based on the path model, increases in both
      diet and exercise self-efficacy had significant effects on increases in health
      promoting behaviour. Increases in diet self-efficacy had a significant indirect
      effect on initial weight loss via increases in health-promoting behaviour.
      Increases in health-promoting behaviour had a significant effect on initial
      weight loss. CONCLUSION: Among women with abdominal obesity, increased diet self
      efficacy and health-promoting behaviour were predictors of initial weight loss. A
      mechanism by which increased diet self-efficacy predicts initial weight loss may
      be partially attributable to health-promoting behavioural change. However, more
      work is still needed to verify causality. Based on the current findings,
      intensive nursing strategies for increasing self-efficacy for weight control and
      health-promoting behaviour may be essential components for better weight loss in
      the initial stage of a weight management intervention.

PMID- 25560746
TI  - TMSI-promoted vinylogous Michael addition of siloxyfuran to 2-substituted
      chromones: a general approach for the total synthesis of chromanone lactone
      natural products.
AB  - A concise and facile synthetic protocol for the construction of the 2-gamma
      lactone chromanone skeleton has been achieved through a TMSI-promoted
      diastereoselective vinylogous Michael addition of siloxyfuran to 2-substituted
      chromones. The applicability of this method is demonstrated through the rapid
      access to the total syntheses of (+/-)-microdiplodiasone, (+/-)-lachnone C, and
      (+/-)-gonytolides C and G. 

PMID- 25560745
TI  - Importance of Viral Sequence Length and Number of Variable and Informative Sites
      in Analysis of HIV Clustering.
AB  - To improve the methodology of HIV cluster analysis, we addressed how analysis of
      HIV clustering is associated with parameters that can affect the outcome of viral
      clustering. The extent of HIV clustering and tree certainty was compared between
      401 HIV-1C near full-length genome sequences and subgenomic regions retrieved
      from the LANL HIV Database. Sliding window analysis was based on 99 windows of
      1,000 bp and 45 windows of 2,000 bp. Potential associations between the extent of
      HIV clustering and sequence length and the number of variable and informative
      sites were evaluated. The near full-length genome HIV sequences showed the
      highest extent of HIV clustering and the highest tree certainty. At the bootstrap
      threshold of 0.80 in maximum likelihood (ML) analysis, 58.9% of near full-length
      HIV-1C sequences but only 15.5% of partial pol sequences (ViroSeq) were found in
      clusters. Among HIV-1 structural genes, pol showed the highest extent of
      clustering (38.9% at a bootstrap threshold of 0.80), although it was
      significantly lower than in the near full-length genome sequences. The extent of
      HIV clustering was significantly higher for sliding windows of 2,000 bp than
      1,000 bp. We found a strong association between the sequence length and
      proportion of HIV sequences in clusters, and a moderate association between the
      number of variable and informative sites and the proportion of HIV sequences in
      clusters. In HIV cluster analysis, the extent of detectable HIV clustering is
      directly associated with the length of viral sequences used, as well as the
      number of variable and informative sites. Near full-length genome sequences could
      provide the most informative HIV cluster analysis. Selected subgenomic regions
      with a high extent of HIV clustering and high tree certainty could also be
      considered as a second choice. 

PMID- 25560747
TI  - Sentinel lymph node localization with contrast-enhanced ultrasound and an I-125
      seed: an ideal prospective development study.
AB  - INTRODUCTION: Our aim was to evaluate the development of microbubble-enhanced
      sentinel lymph node (SLN) localization with placement of an I-125 seed in breast
      cancer patients as a potential alternative for SLN localization with nanocolloid.
      The study is conducted and reported following the IDEAL recommendations for
      evaluation of a new technique at Stage 2a (Prospective Development Study).
      METHODS: Fourteen consecutive patients with 15 lesions underwent microbubble
      enhanced SLN localization with placement of an I-125 seed after the standard SLN
      localization (nanocolloid). We placed an I-125 seed within or near the SLN
      following its identification using intradermally injected microbubbles. The SLN
      was excised guided by nanocolloid and the SLN containing the I-125 seed was
      searched for. All technical modifications are described and standardized outcomes
      measured. RESULTS: Twelve (80%) microbubble procedures with I-125 seed placements
      were technically successful. In three cases no microbubble-enhancing lymph node
      could be detected. Intraoperatively, we found nine I-125 seeds within 0.5 cm of
      the nanocolloid confirmed SLN. One I-125 seed was found next to a non-SLN and two
      I-125 seeds were not near any lymph node. Overall, the procedure was successful
      in 60% (9 out of 15) of the cases. CONCLUSION: Given the low success rate, we
      conclude that microbubble-enhanced SLN is not a viable alternative to the
      standard SLN procedure. Modifications to this technique did not improve its
      performance. Planned study (NTR3690
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3690) was stopped early
      due to this conclusion and results reported in order to provide a full and
      transparent record of the evolution of technique.

PMID- 25560748
TI  - Five year experience in management of perforated peptic ulcer and validation of
      common mortality risk prediction models - are existing models sufficient? A
      retrospective cohort study.
AB  - BACKGROUND: Emergency surgery for perforated peptic ulcer (PPU) is associated
      with significant morbidity and mortality. Accurate and early risk stratification
      is important. The primary aim of this study is to validate the various existing
      MRPMs and secondary aim is to audit our experience of managing PPU. METHODS: 332
      patients who underwent emergency surgery for PPU at a single intuition from
      January 2008 to December 2012 were studied. Clinical and operative details were
      collected. Four MRPMs: American Society of Anesthesiology (ASA) score, Boey's
      score, Mannheim peritonitis index (MPI) and Peptic ulcer perforation (PULP) score
      were validated. RESULTS: Median age was 54.7 years (range 17-109 years) with male
      predominance (82.5%). 61.7% presented within 24 h of onset of abdominal pain.
      Median length of stay was 7 days (range 2-137 days). Intra-abdominal collection,
      leakage, re-operation and 30-day mortality rates were 8.1%, 2.1%, 1.2% and 7.2%
      respectively. All the four MRPMs predicted intra-abdominal collection and
      mortality; however, only MPI predicted leak (p = 0.01) and re-operation (p =
      0.02) rates. The area under curve for predicting mortality was 75%, 72%, 77.2%
      and 75% for ASA score, Boey's score, MPI and PULP score respectively. DISCUSSION
      AND CONCLUSION: Emergency surgery for PPU has low morbidity and mortality in our
      experience. MPI is the only scoring system which predicts all - intra-abdominal
      collection, leak, reoperation and mortality. All four MRPMs had a similar and
      fair accuracy to predict mortality, however due to geographic and demographic
      diversity and inherent weaknesses of exiting MRPMs, quest for development of an
      ideal model should continue.

PMID- 25560749
TI  - Three-dimensional (3D) simulation versus two-dimensional (2D) enhances surgical
      skills acquisition in standardised laparoscopic tasks: a before and after study.
AB  - INTRODUCTION: The aim of this study is to determine if simulated 3D vision
      improves the speed and accuracy of laparoscopic phantom tasks in laparoscopically
      naive subjects. METHODS: Thirty laparoscopically naive subjects were divided into
      matched groups according to age, sex, hand dominance and initial scores on a
      standardised visio-spatial test. Laprotrain((c)) laparoscopic simulators were
      used, one attached to the standard 2D monitor and the other to a simulated 3D
      monitor and 3D glasses were worn by the subjects in this group. Five standardised
      laparoscopic tasks were developed and the subjects underwent testing on four
      separate occasions with more than 24 h between sessions. The subjects were timed
      for each task and errors were recorded by two independent observers. In the
      second part of the study, subjects switched to the opposite group and task times
      and errors were again recorded. Statistical differences between groups were
      calculated using student t-test and Fisher's exact test. RESULTS: There were
      fifteen subjects in each group with no significant difference in demographic or
      psychometric variables. The mean time to complete the tasks was faster in the 3D
      group compared with the 2D group. There was a lower rate of errors noted in the
      3D group compared with the 2D group but this only reached statistical
      significance in two of the five laparoscopic tasks. In the crossover study,
      subjects who had trained on simulated 3D had better task times and fewer errors
      compared to those who had trained on 2D simulators. DISCUSSION & CONCLUSION:
      Training on a simulated 3D model (compared to standard 2D) allows trainees to
      reach proficiency sooner.

PMID- 25560750
TI  - Miniaturized extracorporeal circulation versus off-pump coronary artery bypass
      grafting: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Controversies exist whether off-pump coronary artery bypass (OPCAB)
      is superior to miniaturized extracorporeal circulation (MECC) in reducing
      deleterious effects of cardiopulmonary bypass as only a number of smaller
      randomized controlled trials (RCT) currently provide a limited evidence base. The
      main purpose of conducting the present meta-analysis was to overcome the expected
      low power in RCTs in an attempt to establish whether MECC is comparable to OPCAB.
      METHODS: A MEDLINE/PubMed search was conducted to identify eligible RCTs. A
      pooled summary effect estimate was calculated by means of Mantel-Haenszel method.
      RESULTS: The search yielded 7 RCTs included in this meta-analysis enrolling 271
      patients in the OPCAB group and 279 in the MECC group. The OPCAB and MECC groups
      were comparable in terms of incidence of in-hospital mortality (Risk Difference
      [RD] 0.01; 95%CI -0.02, 0.03; P = 0.55; I(2) = 0%), stroke (RD -0.01; 95%CI 
      0.05, 0.04; P = 0.69; I(2) = 0%), need for renal replacement therapy (RD 0.00; 
      0.06, 0.06; P = 1; I(2) = 0%), postoperative atrial fibrillation (RD -0.03; 
      0.17, 0.10; P = 0.64; I(2) = 0%), re-exploration for bleeding (RD -0.01; 95%CI 
      0.03, 0.02; P = 0.65; I(2) = 0%), transfusion rate (RD -0.01; 95%CI -0.03, 0.02;
      P = 0.65; I(2) = 0%) and the amount of blood loss (weighted mean difference -25
      mL; 95%CI -71, 21; P = 0.28; I(2) = 0%). CONCLUSIONS: Using a meta-analytic
      approach, MECC achieves clinical results comparable to OPCAB including
      postoperative blood loss and blood transfusion requirement. On the basis of our
      findings, MECC should be considered as a valid alternative to OPCAB in order to
      reduce surgical morbidity of conventional cardiopulmonary bypass.

PMID- 25560752
TI  - An overview of effective therapies and recent advances in biomarkers for chronic
      liver diseases and associated liver cancer.
AB  - Chronic liver diseases (CLDs) such as hepatitis, alcoholic liver disease,
      nonalcoholic fatty liver, and their downstream effect cancer affect more than a
      billion of people around the world both symptomatically and asymptomatically. The
      major limitation for early detection and suitable medical management of CLDs and
      liver cancer is either the absent of symptoms or their similar manifestations as
      other diseases. This detection impediment has led to a steady increase in the
      number of people suffering from CLDs with an ultimate outcome of liver failure
      and undergoing transplantation. A better understanding of CLD pathogenesis has
      helped us to develop novel therapies for patients who are at greatest risk for
      CLD progression to the most serious disease cancer. With the discovery of
      aberrant molecular pathways in CLDs, it is now possible to delineate a road map
      for selecting targeted therapies for CLDs. Technological advances in imaging as
      well as the availability of several stable, sensitive, early, noninvasive
      biomarkers for distinguishing different stages of CLDs and cancer have greatly
      facilitated both drug target identification and real-time monitoring of response
      to therapy. Biomarkers are the most useful in clinical practice for liver
      diseases like hepatocellular carcinoma (HCC), which is associated with secretion
      of various tumor-related proteins or nucleotides in peripheral circulation. The
      need for the identification of CLD biomarkers remains high. This article reviews
      the etiologies of CLDs, the results of recent clinical trials of treatments for
      CLDs, and development of noninvasive methodologies for detecting CLDs and
      monitoring their progression toward HCC. 

PMID- 25560753
TI  - Vitamin D: a target for improving post-stroke prognosis?

PMID- 25560751
TI  - "Friending" teens: systematic review of social media in adolescent and young
      adult health care.
AB  - BACKGROUND: Social media has emerged as a potentially powerful medium for
      communication with adolescents and young adults around their health choices.
      OBJECTIVE: The goal of this systematic review is to identify research on the use
      of social media for interacting with adolescents and young adults in order to
      achieve positive health outcomes. METHODS: A MEDLINE/PubMed electronic database
      search was performed between January 1, 2002 and October 1, 2013, using terms to
      identify peer-reviewed research in which social media and other Web 2.0
      technologies were an important feature. We used a systematic approach to retrieve
      papers and extract relevant data. RESULTS: We identified 288 studies involving
      social media, of which 87 met criteria for inclusion; 75 studies were purely
      observational and 12 were interventional. The ways in which social media was
      leveraged by these studies included (1) observing adolescent and young adult
      behavior (n=77), (2) providing health information (n=13), (3) engaging the
      adolescent and young adult community (n=17), and (4) recruiting research
      participants (n=23). Common health topics addressed included high-risk sexual
      behaviors (n=23), alcohol, tobacco, and other drug use (n=19), Internet safety
      (n=8), mental health issues (n=18), medical conditions (n=11), or other specified
      issues (n=12). Several studies used more than one social media platform and
      addressed more than one health-related topic. CONCLUSIONS: Social media
      technologies offer an exciting new means for engaging and communicating with
      adolescents and young adults; it has been successfully used to engage this age
      group, identify behaviors, and provide appropriate intervention and education.
      Nevertheless, the majority of studies to date have been preliminary and limited
      in their methodologies, and mostly center around evaluating how adolescents and
      young adults use social media and the resulting implications on their health.
      Although these explorations are essential, further exploration and development of
      these strategies into building effective interventions is necessary.

PMID- 25560754
TI  - Cigarette price variation around high schools: evidence from Washington DC.
AB  - This study examines lowest cigarette prices in all tobacco retail outlets in
      Washington D.C. (n=750) in relation to the type and number of high schools
      nearby, controlling for confounders. The lowest overall and Newport menthol
      prices were significantly lower at outlets near public non-charter and charter
      schools compared with outlets near private schools. Given higher smoking
      prevalence and more price-sensitive youth subgroups in U.S. public schools,
      exposure to low prices may contribute to tobacco-related health disparities in
      minority and low-income populations. Tobacco taxes combined with policies to
      minimize the increasing use of price as a marketing tool are critical. 

PMID- 25560755
TI  - Distinctive transcriptome alterations of prefrontal pyramidal neurons in
      schizophrenia and schizoaffective disorder.
AB  - Schizophrenia is associated with alterations in working memory that reflect
      dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory
      depends on the activity of excitatory pyramidal cells in DLPFC layer 3 and, to a
      lesser extent, in layer 5. Although many studies have profiled gene expression in
      DLPFC gray matter in schizophrenia, little is known about cell-type-specific
      transcript expression in these two populations of pyramidal cells. We
      hypothesized that interrogating gene expression, specifically in DLPFC layer 3 or
      5 pyramidal cells, would reveal new and/or more robust schizophrenia-associated
      differences that would provide new insights into the nature of pyramidal cell
      dysfunction in the illness. We also sought to determine the impact of other
      variables, such as a diagnosis of schizoaffective disorder or medication use at
      the time of death, on the patterns of gene expression in pyramidal neurons.
      Individual pyramidal cells in DLPFC layers 3 or 5 were captured by laser
      microdissection from 36 subjects with schizophrenia or schizoaffective disorder
      and matched normal comparison subjects. The mRNA from cell collections was
      subjected to transcriptome profiling by microarray followed by quantitative PCR
      validation. Expression of genes involved in mitochondrial (MT) or ubiquitin
      proteasome system (UPS) functions were markedly downregulated in the patient
      group (P-values for MT-related and UPS-related pathways were <10(-7) and <10(-5),
      respectively). MT-related gene alterations were more prominent in layer 3
      pyramidal cells, whereas UPS-related gene alterations were more prominent in
      layer 5 pyramidal cells. Many of these alterations were not present, or found to
      a lesser degree, in samples of DLPFC gray matter from the same subjects,
      suggesting that they are pyramidal cell specific. Furthermore, these findings
      principally reflected alterations in the schizophrenia subjects were not present
      or present to a lesser degree in the schizoaffective disorder subjects (diagnosis
      of schizoaffective disorder was the most significant covariate, P<10(-6)) and
      were not attributable to factors frequently comorbid with schizophrenia. In
      summary, our findings reveal expression deficits in MT- and UPS-related genes
      specific to layer 3 and/or layer 5 pyramidal cells in the DLPFC of schizophrenia
      subjects. These cell type-specific transcriptome signatures are not
      characteristic of schizoaffective disorder, providing a potential molecular
      cellular basis of differences in clinical phenotypes. 

PMID- 25560756
TI  - Copy number variation in bipolar disorder.
AB  - Large (>100 kb), rare (<1% in the population) copy number variants (CNVs) have
      been shown to confer risk for schizophrenia (SZ), but the findings for bipolar
      disorder (BD) are less clear. In a new BD sample from the United Kingdom
      (n=2591), we have examined the occurrence of CNVs and compared this with
      previously reported samples of 6882 SZ and 8842 control subjects. When combined
      with previous data, we find evidence for a contribution to BD for three SZ
      associated CNV loci: duplications at 1q21.1 (P=0.022), deletions at 3q29 (P=0.03)
      and duplications at 16p11.2 (P=2.3 * 10(-4)). The latter survives multiple
      testing correction for the number of recurrent large CNV loci in the genome.
      Genes in 20 regions (total of 55 genes) were enriched for rare exonic CNVs among
      BD cases, but none of these survives correction for multiple testing. Finally,
      our data provide strong support for the hypothesis of a lesser contribution of
      very large (>500 kb) CNVs in BD compared with SZ, most notably for deletions >1
      Mb (P=9 * 10(-4)).

PMID- 25560757
TI  - Rapid antidepressants stimulate the decoupling of GABA(B) receptors from
      GIRK/Kir3 channels through increased protein stability of 14-3-3eta.
AB  - A single injection of N-methyl-D-aspartate receptor (NMDAR) antagonists produces
      a rapid antidepressant response. Lasting changes in the synapse structure and
      composition underlie the effectiveness of these drugs. We recently discovered
      that rapid antidepressants cause a shift in the gamma-aminobutyric acid receptor
      (GABABR) signaling pathway, such that GABABR activation shifts from opening
      inwardly rectifiying potassium channels (Kir/GIRK) to increasing resting
      dendritic calcium signal and mammalian Target of Rapamycin activity. However,
      little is known about the molecular and biochemical mechanisms that initiate this
      shift. Herein, we show that GABABR signaling to Kir3 (GIRK) channels decreases
      with NMDAR blockade. Blocking NMDAR signaling stabilizes the adaptor protein 14-3
      3eta, which decouples GABABR signaling from Kir3 and is required for the rapid
      antidepressant efficacy. Consistent with these results, we find that key proteins
      involved in GABABR signaling bidirectionally change in a depression model and
      with rapid antidepressants. In socially defeated rodents, a model for depression,
      GABABR and 14-3-3eta levels decrease in the hippocampus. The NMDAR antagonists
      AP5 and Ro-25-6981, acting as rapid antidepressants, increase GABABR and 14-3
      3eta expression and decrease Kir3.2. Taken together, these data suggest that the
      shift in GABABR function requires a loss of GABABR-Kir3 channel activity mediated
      by 14-3-3eta. Our findings support a central role for 14-3-3eta in the efficacy
      of rapid antidepressants and define a critical molecular mechanism for activity
      dependent alterations in GABABR signaling. 

PMID- 25560758
TI  - Identification and functional characterization of rare SHANK2 variants in
      schizophrenia.
AB  - Recent genetic data on schizophrenia (SCZ) have suggested that proteins of the
      postsynaptic density of excitatory synapses have a role in its etiology.
      Mutations in the three SHANK genes encoding for postsynaptic scaffolding proteins
      have been shown to represent risk factors for autism spectrum disorders and other
      neurodevelopmental disorders. To address if SHANK2 variants are associated with
      SCZ, we sequenced SHANK2 in 481 patients and 659 unaffected individuals. We
      identified a significant increase in the number of rare (minor allele
      frequency<1%) SHANK2 missense variants in SCZ individuals (6.9%) compared with
      controls (3.9%, P=0.039). Four out of fifteen non-synonymous variants identified
      in the SCZ cohort (S610Y, R958S, P1119T and A1731S) were selected for functional
      analysis. Overexpression and knockdown-rescue experiments were carried out in
      cultured primary hippocampal neurons with a major focus on the analysis of
      morphological changes. Furthermore, the effect on actin polymerization in
      fibroblast cell lines was investigated. All four variants revealed functional
      impairment to various degrees, as a consequence of alterations in spine volume
      and clustering at synapses and an overall loss of presynaptic contacts. The
      A1731S variant was identified in four unrelated SCZ patients (0.83%) but not in
      any of the sequenced controls and public databases (P=4.6 * 10(-5)). Patients
      with the A1731S variant share an early prodromal phase with an insidious onset of
      psychiatric symptoms. A1731S overexpression strongly decreased the SHANK2-Bassoon
      positive synapse number and diminished the F/G-actin ratio. Our results strongly
      suggest a causative role of rare SHANK2 variants in SCZ and underline the
      contribution of SHANK2 gene mutations in a variety of neuropsychiatric disorders.

PMID- 25560759
TI  - Acute tianeptine treatment selectively modulates neuronal activation in the
      central nucleus of the amygdala and attenuates fear extinction.
AB  - Antidepressant drugs are commonly prescribed treatments for anxiety disorders,
      and there is growing interest in understanding how these drugs impact fear
      extinction because extinction learning is pivotal to successful exposure-based
      therapy (EBT). A key objective within this domain is understanding how
      antidepressants alter the activation of specific elements of the limbic-based
      network that governs such fear processing. Chronic treatment with the
      antidepressant tianeptine has been shown to reduce the acquisition of extinction
      learning in rats, yet the drug's acute influence on activation in prefrontal and
      amygdalar regions, and on extinction learning are not well understood. To assess
      its influence on cellular activation, rats were injected with tianeptine and Fos
      immunoreactivity was measured in these regions. Acute tianeptine treatment
      selectively altered Fos expression within subdivisions of the central nucleus of
      the amygdala (CEA) in a bidirectional manner that varied in relation to ongoing
      activation within the capsular subdivision and its prefrontal and intra-amygdalar
      inputs. This pattern of results suggests that the drug can conditionally modulate
      the activation of CEA subdivisions, which contain microcircuits strongly
      implicated in fear processing. The effect of acute tianeptine was also examined
      with respect to the acquisition, consolidation and expression of fear extinction
      in rats. Acute tianeptine attenuated extinction learning as well as the recall of
      extinction memory, which underscores that acute dosing with the drug could alter
      learning during EBT. Together these findings provide a new perspective for
      understanding the mechanism supporting tianeptine's clinical efficacy, as well as
      its potential influence on CEA-based learning mechanisms. 

PMID- 25560760
TI  - Pharmacologic blockade of 12/15-lipoxygenase ameliorates memory deficits, Abeta
      and tau neuropathology in the triple-transgenic mice.
AB  - The 12/15-lipoxygenase (12/15LO) enzyme is widely distributed within the central
      nervous system. Previous work showed that this protein is upregulated in
      Alzheimer's disease (AD), and plays an active role in the development of brain
      amyloidosis in amyloid beta (Abeta)-precursor protein transgenic mice (Tg2576).
      In the present paper, we studied the effect of its pharmacologic inhibition on
      the AD-like phenotype of a mouse model with plaques and tangles, the triple
      transgenic mice. Compared with mice receiving placebo, the group treated with
      PD146176, a specific 12/15LO inhibitor, manifested a significant improvement of
      their memory deficits. The same animals had a significant reduction in Abeta
      levels and deposition, which was secondary to a decrease in the beta-secretase
      pathway. In addition, while total tau-soluble levels were unchanged for both
      groups, PD146176-treated mice had a significant reduction in its phosphorylation
      state and insoluble fraction, which specifically associated with decrease in
      stress-activated protein kinase/c-Jun N-terminal kinase activity. In vitro study
      showed that the effect on tau and Abeta were independent from each other. These
      data establish a functional role for 12/15LO 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 12/15LO inhibitors as novel
      therapeutic agents for AD. 

PMID- 25560761
TI  - Evidence against dopamine D1/D2 receptor heteromers.
AB  - Hetero-oligomers of G-protein-coupled receptors have become the subject of
      intense investigation, because their purported potential to manifest signaling
      and pharmacological properties that differ from the component receptors makes
      them highly attractive for the development of more selective pharmacological
      treatments. In particular, dopamine D1 and D2 receptors have been proposed to
      form hetero-oligomers that couple to Galphaq proteins, and SKF83959 has been
      proposed to act as a biased agonist that selectively engages these receptor
      complexes to activate Galphaq and thus phospholipase C. D1/D2 heteromers have
      been proposed as relevant to the pathophysiology and treatment of depression and
      schizophrenia. We used in vitro bioluminescence resonance energy transfer, ex
      vivo analyses of receptor localization and proximity in brain slices, and
      behavioral assays in mice to characterize signaling from these putative
      dimers/oligomers. We were unable to detect Galphaq or Galpha11 protein coupling
      to homomers or heteromers of D1 or D2 receptors using a variety of biosensors.
      SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor
      knockout (KO) mice, verifying a key role for D1-like receptor activation. In
      contrast, SKF83959-induced motor responses were intact in D2 receptor and Galphaq
      KO mice, as well as in knock-in mice expressing a mutant Ala(286)-CaMKIIalpha
      that cannot autophosphorylate to become active. Moreover, we found that, in the
      shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor
      promoters are both active, the receptor proteins are segregated and do not form
      complexes. These data are not compatible with SKF83959 signaling through Galphaq
      or through a D1/D2 heteromer and challenge the existence of such a signaling
      complex in the adult animals that we used for our studies. 

PMID- 25560762
TI  - Brain abnormalities in bipolar disorder detected by quantitative T1rho mapping.
AB  - Abnormal metabolism has been reported in bipolar disorder, however, these studies
      have been limited to specific regions of the brain. To investigate whole-brain
      changes potentially associated with these processes, we applied a magnetic
      resonance imaging technique novel to psychiatric research, quantitative mapping
      of T1 relaxation in the rotating frame (T1rho). This method is sensitive to
      proton chemical exchange, which is affected by pH, metabolite concentrations and
      cellular density with high spatial resolution relative to alternative techniques
      such as magnetic resonance spectroscopy and positron emission tomography. Study
      participants included 15 patients with bipolar I disorder in the euthymic state
      and 25 normal controls balanced for age and gender. T1rho maps were generated and
      compared between the bipolar and control groups using voxel-wise and regional
      analyses. T1rho values were found to be elevated in the cerebral white matter and
      cerebellum in the bipolar group. However, volumes of these areas were normal as
      measured by high-resolution T1- and T2-weighted magnetic resonance imaging.
      Interestingly, the cerebellar T1rho abnormalities were normalized in participants
      receiving lithium treatment. These findings are consistent with metabolic or
      microstructural abnormalities in bipolar disorder and draw attention to roles of
      the cerebral white matter and cerebellum. This study highlights the potential
      utility of high-resolution T1rho mapping in psychiatric research. 

PMID- 25560764
TI  - MiR-540 as a novel adipogenic inhibitor impairs adipogenesis via suppression of
      PPARgamma.
AB  - A better understanding of the molecular mechanisms in adipogenesis may provide
      new insights into adipose tissue-related diseases. Recently, microRNAs (miRNAs)
      have emerged as a class of epigenetic regulators of stem cell differentiation. In
      this study, we found that miR-540 was an essential negative regulator of
      adipogenic differentiation in adipose tissue-derived stromal cells (ADSCs).
      Lentivirus-mediated overexpression of miR-540 resulted in blockade of the
      expression of C/EBP-alpha and PPARgamma, the two master transcription factors of
      adipogenesis, and deficient lipid accumulation, whereas inhibition of miR-540
      promoted these processes. Target gene reporter assays showed that miR-540
      directly targeted the 3'-untranslated region (3'UTR) of PPARgamma, resulting in a
      decrease of PPARgamma protein expression. Collectively, these data suggest that
      miR-540 represents a new adipogenic inhibitor by, at least in part, targeting
      PPARgamma.

PMID- 25560763
TI  - Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice.
AB  - Disruptions in circadian rhythms and dopaminergic activity are involved in the
      pathophysiology of bipolar disorder, though their interaction remains unclear.
      Moreover, a lack of animal models that display spontaneous cycling between mood
      states has hindered our mechanistic understanding of mood switching. Here, we
      find that mice with a mutation in the circadian Clock gene (ClockDelta19) exhibit
      rapid mood-cycling, with a profound manic-like phenotype emerging during the day
      following a period of euthymia at night. Mood-cycling coincides with abnormal
      daytime spikes in ventral tegmental area (VTA) dopaminergic activity, tyrosine
      hydroxylase (TH) levels and dopamine synthesis. To determine the significance of
      daytime increases in VTA dopamine activity to manic behaviors, we developed a
      novel optogenetic stimulation paradigm that produces a sustained increase in
      dopamine neuronal activity and find that this induces a manic-like behavioral
      state. Time-dependent dampening of TH activity during the day reverses manic
      related behaviors in ClockDelta19 mice. Finally, we show that CLOCK acts as a
      negative regulator of TH transcription, revealing a novel molecular mechanism
      underlying cyclic changes in mood-related behavior. Taken together, these studies
      have identified a mechanistic connection between circadian gene disruption and
      the precipitation of manic episodes in bipolar disorder. 

PMID- 25560766
TI  - Is there a male-specific effect on hypertension?

PMID- 25560765
TI  - Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with a
      loss-of-function mutation in CDK5.
AB  - Lissencephaly comprises a heterogeneous group of developmental brain disorders of
      varying severity, involving abnormal cortical gyration. We studied a highly
      consanguineous Israeli Moslem family with a lethal form of autosomal recessive
      lissencephaly with cerebellar hypoplasia (LCH). Using microarray-based
      homozygosity mapping in the reported family, combined with whole exome sequencing
      in one affected infant, we identified a homozygous splice site mutation
      g.IVS8+1G>A in cyclin-dependent kinase 5 (CDK5), causing complete skipping of
      exon 8, and leading to a frame shift and premature stop codon (p.V162SfsX19). The
      mutation co-segregated with the disease phenotype in all 29 study participants (4
      patients and 25 healthy relatives), and was not identified in 200 ethnically
      matched control chromosomes. The p.V162SfsX19 mutation causes lack of endogenous
      CDK5 expression in affected dermal fibroblasts and brain tissue at the mRNA and
      protein levels, consistent with nonsense-mediated mRNA decay. Functional analysis
      of the p.V162SfsX19 mutation, using a yeast complementation assay, showed loss-of
      function of the mutant CDK5 gene product, thereby implicating its role in the
      pathogenesis of autosomal recessive LCH in the studied family. 

PMID- 25560768
TI  - Tunable ultrasmall visible-to-extended near-infrared emitting silver sulfide
      quantum dots for integrin-targeted cancer imaging.
AB  - The large size of many near-infrared (NIR) fluorescent nanoparticles prevents
      rapid extravasation from blood vessels and subsequent diffusion to tumors. This
      confines in vivo uptake to the peritumoral space and results in high liver
      retention. In this study, we developed a viscosity modulated approach to
      synthesize ultrasmall silver sulfide quantum dots (QDs) with distinct tunable
      light emission from 500 to 1200 nm and a QD core diameter between 1.5 and 9 nm.
      Conjugation of a tumor-avid cyclic pentapeptide (Arg-Gly-Asp-DPhe-Lys) resulted
      in monodisperse, water-soluble QDs (hydrodynamic diameter < 10 nm) without loss
      of the peptide's high binding affinity to tumor-associated integrins (KI = 1.8
      nM/peptide). Fluorescence and electron microscopy showed that selective integrin
      mediated internalization was observed only in cancer cells treated with the
      peptide-labeled QDs, demonstrating that the unlabeled hydrophilic nanoparticles
      exhibit characteristics of negatively charged fluorescent dye molecules, which
      typically do not internalize in cells. The biodistribution profiles of
      intravenously administered QDs in different mouse models of cancer reveal an
      exceptionally high tumor-to-liver uptake ratio, suggesting that the small sized
      QDs evaded conventional opsonization and subsequent high uptake in the liver and
      spleen. The seamless tunability of the QDs over a wide spectral range with only a
      small increase in size, as well as the ease of labeling the bright and
      noncytotoxic QDs with biomolecules, provides a platform for multiplexing
      information, tracking the trafficking of single molecules in cells, and
      selectively targeting disease biomarkers in living organisms without premature QD
      opsonization in circulating blood. 

PMID- 25560769
TI  - Structure-based design and synthesis of a bivalent iminobiotin analog showing
      strong affinity toward a low immunogenic streptavidin mutant.
AB  - The streptavidin/biotin interaction has been widely used as a useful tool in
      research fields. For application to a pre-targeting system, we previously
      developed a streptavidin mutant that binds to an iminobiotin analog while
      abolishing affinity for natural biocytin. Here, we design a bivalent iminobiotin
      analog that shows 1000-fold higher affinity than before, and determine its
      crystal structure complexed with the mutant protein. 

PMID- 25560767
TI  - Compound 21, a selective agonist of angiotensin AT2 receptors, prevents
      endothelial inflammation and leukocyte adhesion in vitro and in vivo.
AB  - BACKGROUND AND PURPOSE: Angiotensin AT2 receptors are upregulated in disease
      states such as atherosclerosis and blockade of the AT2 receptors exacerbates
      plaque formation. Direct stimulation of these receptors is anti-atherogenic but
      the mechanisms and pathways involved remain unknown. We examined the effect of
      direct AT2 receptor stimulation with Compound 21 (C21) on the leukocyte adhesion
      cascade in vitro, right through to plaque formation in vivo. EXPERIMENTAL
      APPROACH: Effects of C21 on TNFalpha-induced inflammation were assessed in human
      umbilical vein endothelial cells (HUVECs), activation of monocytes, polarisation
      of monocyte-derived macrophages and in intact mouse aortae. KEY RESULTS: C21
      attenuated TNFalpha-induced: monocyte adhesion to cultured HUVECs, adhesion
      molecule expression and abolished TNFalpha-induced ROS production. TNFalpha
      induced NFkappaB translocation from the cytoplasm to the nucleus, essential for
      cytokine production, was prevented by C21. C21 did not influence monocyte
      activation or macrophage polarisation but did reduce TNFalpha and IL-6 mRNA
      expression in M1 macrophages. The anti-inflammatory effects of C21 were abolished
      by an AT2 receptor antagonist confirming that the effects of C21 were AT2
      receptor-mediated. Also, leukocyte adhesion and cytokine gene expression, induced
      by high-fat diet (HFD), was attenuated in ApoE(-/-) mice treated with C21. Plaque
      size and stability were improved with C21 treatment with increased smooth muscle
      cell composition and decreased lipid size, compared with HFD-saline treated mice.
      CONCLUSION AND IMPLICATIONS: C21 prevented TNFalpha-induced and HFD-induced
      vascular inflammation in vitro and in vivo. Our data provide strong evidence that
      the anti-atherosclerotic actions of C21 were due to vascular anti-inflammatory
      effects, mediated by AT2 receptors.

PMID- 25560770
TI  - Major depression induces oxidative stress and platelet hyperaggregability.
AB  - We have previously demonstrated an impairment of intraplatelet L-arginine-nitric
      oxide-cGMP pathway in major depression (MD) associated to platelet dysfunction.
      Here, we evaluated arginase pathway and phosphodiesterase 5 (PDE5) expression in
      platelets, systemic and intraplatelet oxidative status in untreated MD patients,
      and their effects on platelet aggregation. Blood samples were collected from 22
      treatment naive MD patients (31 +/- 2 yr) and 27 healthy subjects (33 +/- 2 yr).
      MD patients presented with an activation of platelet arginase II, which competes
      with L-arginine for the production of nitric oxide (NO). An increase in protein
      carbonylation, overexpression of NADPH oxidase and PDE5, an enzyme that
      inactivates cGMP, was observed in platelets from MD patients compared to
      controls. In this context, platelet hyperaggregability was found in MD patients.
      On the other hand, antioxidant enzymes catalase, glutathione peroxidase and
      superoxide dismutase activities in serum and in platelets did not differ between
      groups. The increased activation of intraplatelet arginase and platelet
      aggregability, in addition to an overexpression of PDE5 and oxidative stress may
      contribute to alterations in L-arginine-NO-cGMP pathway and in platelet function,
      and consequently to the increased thrombotic risk in MD.

PMID- 25560771
TI  - Reply to Millman and Opler.

PMID- 25560773
TI  - Impact of an electronic medical record on the incidence of antiretroviral
      prescription errors and HIV pharmacist reconciliation on error correction among
      hospitalized HIV-infected patients.
AB  - BACKGROUND: Previous review of admissions from 2009-2011 in our institution found
      a 35.1% error rate in antiretroviral (ART) prescribing, with 55% of errors never
      corrected. Subsequently, our institution implemented a unified electronic medical
      record (EMR) and we developed a medication reconciliation process with an HIV
      pharmacist. We report the impact of the EMR on incidence of errors and of the
      pharmacist intervention on time to error correction. METHODS: Prospective medical
      record review of HIV-infected patients hospitalized for >24 h between 9 March
      2013 and 10 March 2014. An HIV pharmacist reconciled outpatient ART prescriptions
      with inpatient orders within 24 h of admission. Prescribing errors were
      classified and time to error correction recorded. Error rates and time to
      correction were compared to historical data using relative risks (RR) and
      logistic regression models. RESULTS: 43 medication errors were identified in
      31/186 admissions (16.7%). The incidence of errors decreased significantly after
      EMR (RR 0.47, 95% CI 0.34, 0.67). Logistic regression adjusting for gender and
      race/ethnicity found that errors were 61% less likely to occur using the EMR (95%
      CI 40%, 75%; P<0.001). All identified errors were corrected, 65% within 24 h and
      81.4% within 48 h. Compared to historical data where only 31% of errors were
      corrected in <24 h and 55% were never corrected, errors were 9.4* more likely to
      be corrected within 24 h with HIV pharmacist intervention (P<0.001). CONCLUSIONS:
      Use of an EMR decreased the error rate by more than 50% but despite this, ART
      errors remained common. HIV pharmacist intervention was key to timely error
      correction.

PMID- 25560772
TI  - Preliminary analysis of positive and negative syndrome scale in ketamine
      associated psychosis in comparison with schizophrenia.
AB  - OBJECTIVE: Studies of the effects of the N-methyl-d-aspartate (NMDA) glutamate
      receptor antagonist, ketamine, have suggested similarities to the symptoms of
      schizophrenia. Our primary goal was to evaluate the dimensions of the Positive
      and Negative Syndrome Scale (PANSS) in ketamine users (acute and chronic)
      compared to schizophrenia patients (early and chronic stages). METHOD: We
      conducted exploratory factor analysis for the PANSS from four groups: 135 healthy
      subject administrated ketamine or saline, 187 inpatients of ketamine abuse; 154
      inpatients of early course schizophrenia and 522 inpatients of chronic
      schizophrenia. Principal component factor analyses were conducted to identify the
      factor structure of the PANSS. RESULTS: Factor analysis yielded five factors for
      each group: positive, negative, cognitive, depressed, excitement or dissociation
      symptoms. The symptom dimensions in two schizophrenia groups were consistent with
      the established five-factor model (Wallwork et al., 2012). The factor structures
      across four groups were similar, with 19 of 30 symptoms loading on the same
      factor in at least 3 of 4 groups. The factors in the chronic ketamine group were
      more similar to the factors in the two schizophrenia groups rather than to the
      factors in the acute ketamine group. Symptom severities were significantly
      different across the groups (Kruskal-Wallis chi(2)(4) = 540.6, p < 0.0001).
      Symptoms in the two ketamine groups were milder than in the two schizophrenia
      groups (Cohen's d = 0.7). CONCLUSION: Our results provide the evidence of
      similarity in symptom dimensions between ketamine psychosis and schizophrenia
      psychosis. The interpretations should be cautious because of potential
      confounding factors.

PMID- 25560774
TI  - Conceptual and practical foundations of patient engagement in research at the
      patient-centered outcomes research institute.
AB  - PURPOSE: To provide an overview of PCORI's approach to engagement in research.
      METHODS: The Patient-Centered Outcomes Research Institute (PCORI) was established
      in 2010 to fund patient-centered comparative effectiveness research. Requirements
      for research funding from PCORI include meaningful engagement of patients and
      other stakeholders in the research. PCORI's approach to engagement in research is
      guided by a conceptual model of patient-centered outcomes research (PCOR), that
      provides a structure for understanding engagement in research. RESULTS: To
      understand and improve engagement in research PCORI is learning from awardees and
      other stakeholders. Those efforts are described along with PCORI's capacity
      building and guidance to awardees via the Engagement Rubric. PCORI's unique model
      of engaging patients and other stakeholders in merit review of funding
      applications is also described. Additional support for learning about engagement
      in research is provided through specific research funding and through PCORI's
      major infrastructure initiative, PCORnet. CONCLUSION: PCORI requires engagement
      of stakeholders in the research it funds. In addition PCORI engages stakeholders
      in activities including review of funding applications and establishment of CER
      research infrastructure through PCORnet. The comprehensive approach to engagement
      is being evaluated to help guide the field toward promising practices in research
      engagement.

PMID- 25560775
TI  - Conceptual structure of the Taiwan Chinese version of the EORTC QLQ-C30.
AB  - OBJECTIVE: This study aimed to evaluate the conceptual structure of the European
      Organization for Research and Treatment of Cancer Quality of Life Core
      Questionnaire 30 (EORTC QLQ-C30) by analyzing data collected from patients with
      major cancers in Taiwan. The conceptual structure underlying QLQ-C30, including
      higher-order factors, was explored by structural equation modeling (SEM).
      METHODS: The Taiwan Chinese version of the EORTC QLQ-C30 was used as the
      measuring instrument. Higher-order models, including mental health/physical
      health, mental function/physical burden, symptom burden/function, single latent
      health-related quality of life, formative symptom burden/function, and formative
      health-related quality of life, were tested. RESULTS: Study subjects included 283
      patients with breast, lung, and nasopharyngeal cancers. The original QLQ-C30
      multi-factorial structure demonstrated poor composite reliability of the
      cognitive function subscale. The formative symptom/burden model was favored by
      model fit indices, further supporting causal-indicator duality, but was
      compromised by unexpected associations between symptomatic subscales and latent
      factors. The formative health-related quality of life was proposed with a single
      second-order latent factor where symptomatic subscales remained formative. Two
      additional symptom measures from the formal cognitive function subscale with the
      formative health-related quality-of-life model were proposed as the alterative
      conceptual structure for the Taiwan Chinese QLQ-C30. CONCLUSIONS: Results of the
      current study represent the complete SEM approach for the EORTC QLQ-C30. The
      formative health-related quality-of-life model with elimination of cognitive
      function enhances the conceptual structure of the Taiwan Chinese version with
      parsimonious fit and interpretability.

PMID- 25560777
TI  - Tribochemical mechanism of amorphous silica asperities in aqueous environment: a
      reactive molecular dynamics study.
AB  - Reactive molecular dynamics (ReaxFF) simulations are used to explore the atomic
      level tribochemical mechanism of amorphous silica (a-SiO2) in a nanoscale, single
      asperity contact in an aqueous environment. These sliding simulations are
      performed in both a phosphoric acid solution and in pure water under different
      normal pressures. The results show that tribochemical processes have profound
      consequences on tribological performance. Water molecules could help avoid direct
      adhesive interaction between a-SiO2 surfaces in pure water under low normal load.
      However, formation and rupture of interfacial siloxane bonds are obviously
      observed under higher normal load. In phosphoric acid solution, polymerization of
      phosphoric acid molecules occurs, yielding oligomers under lower load, and
      tribochemical reactions between the molecules and the sliding surfaces could
      enhance wear under higher load. The bridging oxygen atoms in silica play an
      important role in the formation of interfacial covalent bonds, and hydrogen is
      found to have a weakening effect on these bonds, resulting in the rupture during
      shear-related loading. This work sheds light on tribochemical reactions as a
      mechanism for lubrication and wear in water-based or other tribological systems. 

PMID- 25560776
TI  - Item-level informant discrepancies between children and their parents on the
      PROMIS((r)) pediatric scales.
AB  - OBJECTIVE: The study objective was to describe the individual item-level
      discrepancies between children ages 8-17 years and their parents for the
      PROMIS((r)) pediatric scales. Contextual effects on item-level informant
      discrepancies for the pediatric pain interference items were further analyzed
      conditional on whether the child, the parent, or anyone else in the household
      experienced chronic pain. METHODS: Parallel pediatric self-report and parent
      proxy-report items were completed by approximately 300 parent-child dyads
      depending on form assignment and individual nonresponse. Agreement between parent
      and child responses to individual items was measured using the polychoric
      correlation coefficient and weighted kappa. The Chi-square test of symmetry was
      utilized for a comparison of the pattern of parent-child item discrepancies on
      the response scales, and the differences between the child and parent responses
      on the 1-5 item response scale are summarized . RESULTS: A continuum of higher
      item-level parent-child discrepancies was demonstrated starting with peer
      relationships, anger, anxiety, and depressive symptoms, followed by progressively
      lower parent-child discrepancies for energy, fatigue, asthma impact, pain
      interference, upper extremity, and mobility items. Parent-child discrepancies for
      pain interference items were lower in the context of chronic pain either in the
      child or in the parent. CONCLUSIONS: Parent-child item-level discrepancies were
      lower for more objective or visible items than for items measuring internal
      states or less observable items measuring latent variables such as peer
      relationships and fatigue. Future research should focus on the child and parent
      characteristics that influence domain-specific item-level discrepancies, and
      under what conditions item-level parent-child discrepancies predict child health
      outcomes.

PMID- 25560778
TI  - Influence of physical state of beta-carotene (crystallized versus solubilized) on
      bioaccessibility.
AB  - beta-Carotene has potentially beneficial biological effects. However, its use is
      currently limited because of its low water-solubility, high melting point, and
      low oral bioavailability. This study investigated the influence of physical state
      (crystalline versus solubilized) on the bioaccessibility of beta-carotene using a
      simulated gastrointestinal tract (GIT) model. Three delivery systems were
      compared: (1) beta-carotene predissolved in a nanoemulsion; (2) beta-carotene
      crystals mixed with a nanoemulsion; and (3) beta-carotene crystals mixed with a
      phosphate-buffered saline (PBS). The changes in the microstructure of the
      delivery systems were characterized after each stage of the GIT model. The beta
      carotene bioaccessibility decreased in the order of delivery system 1 ? 2 > 3,
      which indicated that carotenoids solubilized within a oil phase were much more
      bioaccessible than those that formed crystals. This study provides important
      information for developing effective delivery systems for lipophilic bioactive
      components in food and beverage applications. 

PMID- 25560779
TI  - Selective or stepwise removal of deep caries in deciduous molars: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: For treating deep caries lesions, selective or stepwise (one- and two
      step) incomplete excavation seems advantageous compared with complete caries
      removal. However, current evidence regarding the success, as defined by not
      requiring any retreatments, or survival of teeth after different excavations is
      insufficient for definitive recommendation, especially when treating deciduous
      teeth. Moreover, restoration integrity has not been comparatively analyzed
      longitudinally, and neither patients', dentists' or parents' preferences nor the
      clinical long-term costs emanating from both initial and retreatments have been
      reported yet. METHODS/DESIGN: The planned study is a prospective multicenter, two
      arm parallel group, randomized controlled clinical trial comparing selective and
      stepwise excavation in deciduous molars with deep, active caries lesions without
      pulpal symptoms. We will recruit 300 children aged between three and nine-years
      old with a minimum of one such molar. Patients participating in another study, or
      those with systemic diseases, disabilities or known allergies to used materials
      as well patients with teeth expected to exfoliate within the next 18 months will
      be excluded. After inclusion, sequence generation will be performed. Initial
      treatment will follow dental routine. During excavation, leathery, moist and
      reasonably soft dentin will be left in proximity to the pulp followed by adhesive
      restoration of the cavity. Afterwards, patients', dentists' and parents'
      subjective assessment of the treatment will be recorded using visual analogue or
      Likert scales. Re-examination will be performed after six months, and only then
      teeth will be allocated to one of the two interventions. Selectively excavated
      teeth will not be treated further, whilst for stepwise caries removal, a second
      excavation will be performed until only hard dentin remains. Clinical re
      evaluations will be performed after 12, 24 and 36 months. Restorations will be
      reassessed using modified Ryge criteria. Objectively or subjectively required
      retreatments will determine success and survival. Retreatments will be evaluated
      both subjectively and regarding generated costs. DISCUSSION: Based on the results
      of the trial, decision-making for treating deep caries lesions in deciduous
      molars based on multiple criteria should be feasible. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: NCT02232828 (registered on 29 November 2014).

PMID- 25560780
TI  - Antioxidant activity and cytotoxicity on tumour cells of the essential oil from
      Cedronella canariensis var. canariensis (L.) Webb & Berthel. (Lamiaceae).
AB  - Cedronella canariensis is a lemon-scented species of the family Lamiaceae endemic
      to the Canary Islands where it is used in the traditional medicine to prepare
      infusions or inhalations for anti-catarrhal, tonic, diuretic, hypoglycaemiant,
      hypotensive, anti-inflammatory and decongestant of the respiratory tract. In this
      work we investigated for the first time the antioxidant activity of the essential
      oil and its inhibitory effects on tumour cells (A375, MDA-MB-231, HCT 116)
      proliferation by DPPH, ABTS, FRAP and MTT assays, respectively. The oil, analysed
      by GC-ionisation flame detector and GC-MS, was characterised by pinocarvone
      (58.0%) and beta-pinene (10.8%) as the major constituents, being typical of the
      chemotype 'canariensis'. Noteworthy was the cytotoxic activity of the oil against
      the tumour cells examined, with IC50 values of 4.3, 7.3 and 11.4 MUg/mL on A375,
      MDA-MB-231 and HCT 116 tumour cells, respectively, as well as the scavenging
      activity against the ABTS radical (IC50 of 10.5 MUg/mL).

PMID- 25560781
TI  - Salivary interleukin-6 in the detection of oral cancer and precancer.
AB  - AIM: Oral cancer is a major health concern in many parts of the world. Despite
      its low survival rates, when detected early or in the precancer stage, it can
      drastically increase the survival rates. This strongly supports the need for
      sensitive biomarkers to perk up early detection of oral cancers. The aim of the
      study is to estimate whether salivary interleukin-6 (IL-6) can be used as a
      molecular marker to diagnose leukoplakia and oral squamous cell carcinoma (OSCC).
      METHODS: The sample of 75 cases was divided into three groups of 25 patients
      each: group I: oral leukoplakia; group II: OSCC; group III: control group. Saliva
      samples were collected by simple drooling method and the concentration of IL-6
      was determined by using ELISA (enzyme-linked immunosorbent assay) technique.
      RESULTS: When the concentration of salivary IL-6 among the three groups was
      compared, the results were statistically significant ("P" value <0.001).
      CONCLUSION: The increase in salivary IL-6 in leukoplakia and OSCC might point out
      its local production by the tumor cells. The difference in its levels between
      these two lesions might indicate the progression of precancer to cancer. Further
      longitudinal studies with increased sample size are needed to substantiate the
      utility of salivary IL-6 as diagnostic or prognostic marker for oral cancer and
      precancer.

PMID- 25560782
TI  - A review of formulation techniques that impact the disintegration and mechanical
      properties of oradispersible drug delivery technologies.
AB  - The drug treatment of acute disorders such as neuropathic pain, migraines,
      insomnia, vomiting, allergic rhinitis or erectile dysfunction requires an
      immediate pharmacological effect that may be achieved through parenteral drug
      administration. However, the parenteral route is not always convenient for
      reasons that are well known. Therefore, in the recent past there has been a
      barrage of interest in formulating new, non-invasive, reliable and convenient
      oradispersible drug delivery technologies (ODDTs). Research in this area has
      focused extensively on developing ODDTs that are capable of releasing drugs
      immediately when they come into contact with saliva. This disregards the
      necessity of water during administration and several other advantages that is an
      attribute that makes this technology lucrative for groups such as pediatrics,
      geriatrics, psychiatrics and unconscious patients. Many reviews have been
      compiled on the salient features of ODDTs. However, none to date has focused on
      the actual formulation techniques used to produce these technologies and how this
      may impact their disintegration and physical stability for fulfilling their
      purpose. Therefore this review provides a concise incursion on the recent
      formulation techniques, excipients used as well as methods of testing the
      performance of ODDTs and critically assesses these in terms of improving their
      performance. 

PMID- 25560783
TI  - Robot-assisted radical cystectomy and intracorporeal neobladder formation: on the
      way to a standardized procedure.
AB  - BACKGROUND: Robot-assisted radical cystectomy (RARC) with intracorporeal
      diversion has been shown to be feasible in a few centers of excellence worldwide,
      with promising functional and oncologic outcomes. However, it remains unknown
      whether the complexity of the procedure allows its duplication in other non
      pioneer centers. We attempt to address this issue by presenting our cumulative
      experience with RARC and intracorporeal neobladder formation. METHODS: We
      retrospectively identified 62 RARCs in 50 men and 12 women (mean age 63.6 years)
      in two tertiary centers. Intracorporeal Studer neobladders were created,
      duplicating the steps of standard open surgery. Perioperative and postoperative
      variables and complications were analyzed using standardized tools. Functional
      and oncological results were assessed. RESULTS: The mean operative time was 476.9
      min (range, 310 to 690) and blood loss was 385 ml (200 to 800). The mean hospital
      stay was 16.7 (12 to 62) days with no open conversion. Perioperative
      complications were grade II in 15, grade III in 11, and grade IV in 5 patients.
      The mean nodal yield was 22.9 (8 to 46). Positive margins were found in in 6.4%.
      The 90- and 180-day mortality rates were 0% and 3.3%. The average follow-up was
      37.3 months (3 to 52). Continence was achieved in 88% of patients. The cancer
      specific survival rate and overall survival rate were 84% and 71%, respectively.
      CONCLUSIONS: A RARC with intracorporeal neobladder creation is safe and
      reproducible in 'non-pioneer' tertiary centers with robotic expertise with
      acceptable operative time and complications. Further standardization of RARC with
      intracorporeal diversion is a prerequisite for its widespread use.

PMID- 25560785
TI  - Gastrointestinal characterisation and drug solubility determination in animals.
AB  - OBJECTIVES: To characterise the gastrointestinal (GI) environment in rat, rabbit
      and pig for the purpose of determining their utility as animal models for drug
      delivery in humans. METHODS: GI fluid samples were characterised for osmolality,
      surface tension, pH and buffer capacity. The solubility of two model drugs,
      mesalazine (ionisable) and prednisolone (unionisable), were also measured and the
      results were correlated to the physicochemical fluid data. KEY FINDINGS: The
      solubility of the ionisable drug mesalazine was positively correlated to the GI
      pH in all three species and was significantly influenced by the pH difference. In
      contrast, the solubility of the unionisable compound prednisolone was not
      correlated significantly to the changes in pH, buffer capacity, osmolality or
      surface tension. In general, the solubility of prednisolone was constant
      irrespective of the location of the sample in the gut from rabbit and pig;
      however, an unusual trend was observed for the solubility of prednisolone in
      rats. CONCLUSIONS: The results suggest that solubility of ionisable drugs or pH
      responsive formulations is significantly influenced by the differences in pH
      along the GI tract and inter-species differences. It was also found that the data
      on the GI solubility of prednisolone (a neutral compound) in rats might
      overestimate its true value in humans.

PMID- 25560784
TI  - Establishing prostate cancer patient derived xenografts: lessons learned from
      older studies.
AB  - BACKGROUND: Understanding the progression of prostate cancer to androgen
      independence/castrate resistance and development of preclinical testing models
      are important for developing new prostate cancer therapies. This report describes
      studies performed 30 years ago, which demonstrate utility and shortfalls of
      xenografting to preclinical modeling. METHODS: We subcutaneously implanted male
      nude mice with small prostate cancer fragments from transurethral resection of
      the prostate (TURP) from 29 patients. Successful xenografts were passaged into
      new host mice. They were characterized using histology, immunohistochemistry for
      marker expression, flow cytometry for ploidy status, and in some cases by
      electron microscopy and response to testosterone. Two xenografts were karyotyped
      by G-banding. RESULTS: Tissues from 3/29 donors (10%) gave rise to xenografts
      that were successfully serially passaged in vivo. Two, (UCRU-PR-1, which
      subsequently was replaced by a mouse fibrosarcoma, and UCRU-PR-2, which combined
      epithelial and neuroendocrine features) have been described. UCRU-PR-4 line was a
      poorly differentiated prostatic adenocarcinoma derived from a patient who had
      undergone estrogen therapy and bilateral castration after his cancer relapsed.
      Histologically, this comprised diffusely infiltrating small acinar cell carcinoma
      with more solid aggregates of poorly differentiated adenocarcinoma. The
      xenografted line showed histology consistent with a poorly differentiated
      adenocarcinoma and stained positively for prostatic acid phosphatase (PAcP),
      epithelial membrane antigen (EMA) and the cytokeratin cocktail, CAM5.2, with weak
      staining for prostate specific antigen (PSA). The line failed to grow in female
      nude mice. Castration of three male nude mice after xenograft establishment
      resulted in cessation of growth in one, growth regression in another and
      transient growth in another, suggesting that some cells had retained androgen
      sensitivity. The karyotype (from passage 1) was 43-46, XY, dic(1;12)(p11;p11),
      der(3)t(3:?5)(q13;q13), -5, inv(7)(p15q35) x2, +add(7)(p13), add(8)(p22),
      add(11)(p14), add(13)(p11), add(20)(p12), -22, +r4[cp8]. CONCLUSIONS: Xenografts
      provide a clinically relevant model of prostate cancer, although establishing
      serially transplantable prostate cancer patient derived xenografts is challenging
      and requires rigorous characterization and high quality starting material.
      Xenografting from advanced prostate cancer is more likely to succeed, as
      xenografting from well differentiated, localized disease has not been achieved in
      our experience. Strong translational correlations can be demonstrated between the
      clinical disease state and the xenograft model.

PMID- 25560787
TI  - Non-genetic risk factors and their influence on the management of patients in the
      clinic.
AB  - The development of inhibitors is the most serious iatrogenic complication
      affecting patients with haemophilia. This complication is associated with
      impaired vital or functional prognosis, reduced quality of life and increased
      cost of treatment. The reasons why some patients develop antibodies to factor
      replacement and others do not remain unclear. It is however clear that inhibitor
      development results from a complex multifactorial interaction between genetic and
      non-genetic risk factors. Environmental influences implicated in increasing the
      risk of inhibitor formation can be viewed as modifiable risk factors. Therefore,
      identification of the non-genetic risk factors may offer the possibility of
      personalising haemophilia therapy by modifying treatment strategies in high-risk
      patients in the critical early phase of factor VIII exposure. In this article, we
      review the non-genetic factors reported as well as the potential impact of danger
      signals and the different scores for inhibitor development risk stratification. 

PMID- 25560788
TI  - Genetic risk factors for inhibitors in haemophilia A.
AB  - The current most serious side effect of haemophilia treatment is inhibitor
      development. Significant progress has been made over the last decades to
      understand why this complication occurs in some patients and it seems clear that
      both genetic and non-genetic factors are involved. Several issues however remain
      to be settled. A review was undertaken to summarise some key findings regarding
      the current view and available data on genetic markers of potential importance
      within this area. The causative F8 mutation, together with the HLA class II
      alleles, plays a pivotal pathophysiological role in inhibitor development. The
      types of mutation most frequently associated with inhibitors are large deletions,
      nonsense mutations, inversions, small deletions/insertions without A-runs, splice
      site mutations at conserved nucleotides and certain missense mutations. Regarding
      HLA class II allele, it has been hard to consistently identify risk alleles.
      Ethnicity has consistently been associated with inhibitor risk, but the causality
      of this has so far not been resolved. Among immune regulatory molecules, several
      polymorphic molecules have been suggested to be of importance. Most of these need
      additional studies and immune system challenges have to be fully evaluated.
      Inhibitor risk should be further defined, as patients in the future may be
      offered non-immunogenic treatments. 

PMID- 25560789
TI  - Various regimens for prophylactic treatment of patients with haemophilia.
AB  - Haemophilia prophylaxis is superior to on-demand treatment to prevent joint
      damage. 'High-dose prophylaxis' as used in Sweden is more effective in preventing
      arthropathy than an 'intermediate-dose regimen' (the Netherlands) and the
      Canadian tailored primary prophylaxis. Prophylaxis may reduce the risk of
      developing inhibitors. There is no difference in inhibitor risk between plasma
      derived and recombinant factor VIII (rFVIII) products but the Rodin study showed
      increased risk with second-generation rFVIII products. MRI is a new and very
      sensitive tool to detect the symptoms of early arthropathy but some results (soft
      tissue changes in 'bleed-free joints') still need to be investigated. Ultrasound
      is a very helpful method to aid diagnosis especially during the acute phase of a
      bleed. The risk of infection with central venous access remains a matter of
      debate. A fully implanted central venous access device (CVAD) has a significant
      lower risk of infection compared to external CVADs. Patient's age under 6 yr and
      inhibitor presence are additional risk factors for infections. The role of
      arteriovenous fistulae needs to be investigated because significant complications
      have been reported. Disease-specific quality of life instruments are
      complementary to generic instruments evaluating QoL in patients with haemophilia
      and have become important health outcome measures. 

PMID- 25560790
TI  - The ageing patient with haemophilia.
AB  - Older patients with haemophilia (PWH) face many challenges related not only to
      haemophilia but also to general comorbidities associated with ageing. This
      article discusses the clinical experience published about the high prevalence of
      diseases in older PWH. These conditions are managed in the general population by
      healthcare workers with little training in haemophilia. Haemophilic arthropathy
      is common in elderly PWH. Prophylaxis starting at an early age in sufficient dose
      regimens to prevent arthropathy did not occur in patients who are now older than
      around 40 yr. Many PWH above this age thus have limitations in their activities
      of daily life. Cardiovascular diseases have become increasingly common in the
      growing, ageing cohort of PWH. Lifestyle issues such as sexual dysfunction may be
      exacerbated by the medical issues and psychological problems associated with
      haemophilia. Hepatitis C virus is a leading problem in PWH. Coinfection with HIV
      accelerates the progression to end-stage liver disease. Acute and chronic renal
      failure is more common in adult PWH than in general population. Other
      comorbidities are reviewed. The evidence is scarce, so it is imperative to report
      any experience regarding the diagnosis and treatment of these entities, to
      improve the quality of life of older PWH. 

PMID- 25560791
TI  - Prevention and treatment of atherosclerosis in haemophilia - how to balance risk
      of bleeding with risk of ischaemic events.
AB  - Life expectancy for patients with haemophilia (PWH) has significantly increased
      in the last decades, due to improvement of clotting factor replacement therapy.
      However, despite a lower cardiovascular mortality rate and contrasting prevalence
      for non-fatal ischaemic heart disease (IHD), cardiovascular diseases are
      increasing in PWH. The prevalence of cardiovascular risk factors in PWH is as
      prevalent as in the general population, whereas an increased risk of hypertension
      has been observed in some studies. Furthermore, PWH are not protected against
      atherosclerosis. Coronary artery disease treatment is extremely challenging in
      PWH. Two 'institutional' guidelines for the management of IHD in PWH have been
      published. Since these recommendations, the use of new drugs such as prasugrel,
      ticagrelor, bivalirudin, new oral anticoagulants and new drug-eluting stents have
      been recommended in the general population but should be evaluated in PWH. Some
      questions arise: which trough level during long-term single or dual antiplatelet
      treatment (DAT) is really needed? The clinical role of platelet testing remains
      ill defined but may be considered in selected patients. A multidisciplinary
      approach is necessary for the management of IHD in PWH in order to treat the
      patient as any patient according to the cardiological guidelines during the acute
      phase, and long-term management should be discussed. 

PMID- 25560792
TI  - Strategies for inhibitor treatment and costs in the short and long term: a
      critical evaluation of recent clinical studies.
AB  - One important complication of patients with severe haemophilia A is the formation
      of inhibitory antibodies to factor VIII (FVIII). Immune tolerance induction (ITI)
      is the treatment of choice for patients with inhibitors, but this approach is
      successful in about 60% of patients. Treatment of acute bleeding in patients with
      inhibitors is one of the greatest challenges in haemophilia management and is
      costly. Bypassing agents are the mainstay of treatment in these patients. The
      aims of this study were to review the most recent publications concerning the
      costs of inhibitor treatment. We conducted a literature review using PubMed which
      yielded 63 papers analysing the costs of inhibitor management of which 12 were
      suitable for our study. Four of eight studies supported the use of activated
      prothrombin complex concentrate (aPCC) with lower costs, but the remaining four
      studies showed that recombinant factor VIIa (rFVIIa) had a lower average
      treatment cost. Of four ITI studies, two supported lifelong cost-effectiveness of
      ITI vs. bypassing agents and the remaining two papers showed a high cost of
      inhibitor treatment. Dosages, time between onset of bleeding and treatment,
      patient characteristics and the price of drugs are some of the important issues
      that should be considered for further studies. 

PMID- 25560793
TI  - One-stage vs. chromogenic assays in haemophilia A.
AB  - Haemophilia A severity is closely correlated to the factor VIII (FVIII) activity,
      which can be measured in different ways. The original one-stage clotting assay is
      still the most widely used. The two-stage coagulation assay eliminated many of
      the drawbacks of the one-stage assay and was further developed into the
      chromogenic assay, a two-staged test with purified coagulation factors in the
      first stage, and a FXa-specific chromogenic substrate in the second stage. In
      many patients with mild or moderate haemophilia A, there is a discrepancy between
      the one-stage and the two-stage assays. If only the one-stage assay is used, some
      patients will have normal FVIII levels and not be diagnosed as having haemophilia
      or be considered to have a milder bleeding risk than is the case. Other patients
      who have normal FVIII activity will be diagnosed as haemophilia A. All
      haemophilia treatment centre laboratories should have access to both one-stage
      and chromogenic FVIII:C assays. Appropriate standards should be employed to
      enable accurate FVIII:C measurement. Different assays to measure inhibitor
      activity to infused FVIII have been developed since 1959. Inhibitor results based
      on the one-stage or chromogenic FVIII:C assays are well correlated, but the one
      stage assay may be influenced by nonspecific inhibition. 

PMID- 25560794
TI  - Strategies for reducing inhibitor formation in severe haemophilia.
AB  - The greatest barrier to successful haemophilia A care in resource-rich countries
      is the development of inhibitors to therapeutic factor VIII. Children with
      inhibitors suffer through increased bleeding and joint damage as well as frequent
      venepuncture. Costs associated with inhibitors are beyond many healthcare
      systems. Over the last two decades, there has been no improvement in our ability
      to reduce inhibitor development. Current strategies based on early prophylaxis
      and avoidance of immunological danger signals have given rise to conflicting
      results. Registry data suggest an increasing problem. Our understanding of the
      immunological systems involved in inhibitor formation should inform efforts to
      prevent inhibitors. Great efforts with mouse models are being undertaken in this
      field. However, there is no guarantee of the availability of any new agents
      arising from experimental work in the near future. Global immunomodulatory agents
      may be one solution. Compounds with a long history of use in inflammatory
      conditions have demonstrated efficacy in preventing antibodies to protein
      therapeutics both in animal models and in humans. As these compounds have a long
      history of use in humans, including babies, it may be that these agents offer an
      option for reducing inhibitor formation in previously untreated patients. 

PMID- 25560795
TI  - Advantame sweetener preference in C57BL/6J mice and Sprague-Dawley rats.
AB  - Advantame is a new ultrahigh-intensity noncaloric sweetener derived from
      aspartame and approved for human use. Rats and mice are not attracted to the
      taste of aspartame and this study determined their preference for advantame. In
      24-h choice tests with water, C57BL/6J mice and Sprague-Dawley rats were
      indifferent to advantame at concentrations of 0.01, 0.03, and 0.1mM but
      significantly preferred 0.3 and 1mM advantame to water. Both species also
      preferred 1mM advantame to 1mM saccharin in direct choice tests, but preferred
      10mM saccharin to 1mM advantame, which is near the solubility limit for this
      sweetener. Mice also preferred 1mM advantame to 1mM sucralose or acesulfame K,
      but preferred both sweeteners at 10mM to 1mM advantame. In addition, mice
      preferred 1mM advantame to 1 and 10mM aspartame. Thus, advantame is a potent
      sweetener for rodents but, because of limited solubility, is not an effective
      alternative to saccharin, sucralose, or acesulfame K at higher concentrations. 

PMID- 25560796
TI  - Magnetic resonance imaging of tumor with a self-traceable phosphorylcholine
      polymer.
AB  - Polymers are concentration-amplified with respect to the monomeric units. We show
      here that a phosphorylcholine polymer enriched with (13)C/(15)N at the methyl
      groups is self-traceable by multiple-resonance (heteronuclear-correlation) NMR in
      tumor-bearing mice inoculated with the mouse rectal cancer cell line (colon 26).
      Preliminary measurements indicated that the present polymeric nanoprobe was
      satisfactorily distinguished from lipids and detectable with far sub-micromolar
      spectroscopic and far sub-millimolar imaging sensitivities. Detailed ex vivo and
      in vivo studies for the tumor-bearing mice administered the probe with a mean
      molecular weight of 63,000 and a mean size of 13 nm, revealed the following: (1)
      this probe accumulates in the tumor highly selectively (besides renal excretion)
      and efficiently (up to 30% of the injected dose), (2) the tumor can thus be
      clearly in vivo imaged, the lowest clearly imageable dose of the probe being 100
      mg/kg or 2.0 mg/20-g mouse, and (3) the competition between renal excretion and
      tumor accumulation is size-controlled; that is, the larger (higher molecular
      weight) and smaller (lower molecular-weight) portions of the probe undergo tumor
      accumulation and renal excretion, respectively. The observed size dependence
      suggests that the efficient tumor-targeting of the present probe is stimulated
      primarily by the so-called enhanced permeability and retention (EPR) effect, that
      is, size-allowed invasion of the probe into the tumor tissue via defective
      vascular wall. Self-traceable polymers thus open an important area of magnetic
      resonance imaging (MRI) of tumors and may provide a highly potential tool to
      visualize various delivery/localization processes using synthetic polymers.

PMID- 25560797
TI  - Systematic review and cumulative analysis of oncologic and functional outcomes
      after robot-assisted radical cystectomy.
AB  - CONTEXT: Although open radical cystectomy (ORC) is still the standard approach,
      laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy
      (RARC) are increasingly performed. OBJECTIVE: To report on a systematic
      literature review and cumulative analysis of pathologic, oncologic, and
      functional outcomes of RARC in comparison with ORC and LRC. EVIDENCE ACQUISITION:
      Medline, Scopus, and Web of Science databases were searched using a free-text
      protocol including the terms robot-assisted radical cystectomy or da Vinci
      radical cystectomy or robot* radical cystectomy. RARC case series and studies
      comparing RARC with either ORC or LRC were collected. A cumulative analysis was
      conducted. EVIDENCE SYNTHESIS: The searches retrieved 105 papers, 87 of which
      reported on pathologic, oncologic, or functional outcomes. Most series were
      retrospective and had small case numbers, short follow-up, and potential patient
      selection bias. The lymph node yield during lymph node dissection was 19 (range:
      3-55), with half of the series following an extended template (yield range: 11
      55). The lymph node-positive rate was 22%. The performance of lymphadenectomy was
      correlated with surgeon and institutional volume. Cumulative analyses showed no
      significant difference in lymph node yield between RARC and ORC. Positive
      surgical margin (PSM) rates were 5.6% (1-1.5% in pT2 disease and 0-25% in pT3 and
      higher disease). PSM rates did not appear to decrease with sequential case
      numbers. Cumulative analyses showed no significant difference in rates of
      surgical margins between RARC and ORC or RARC and LRC. Neoadjuvant chemotherapy
      use ranged from 0% to 31%, with adjuvant chemotherapy used in 4-29% of patients.
      Only six series reported a mean follow-up of >36 mo. Three-year disease-free
      survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates
      were 67-76%, 68-83%, and 61-80%, respectively. The 5-yr DFS, CSS, and OS rates
      were 53-74%, 66-80%, and 39-66%, respectively. Similar to ORC, disease of higher
      pathologic stage or evidence of lymph node involvement was associated with worse
      survival. Very limited data were available with respect to functional outcomes.
      The 12-mo continence rates with continent diversion were 83-100% in men for
      daytime continence and 66-76% for nighttime continence. In one series, potency
      was recovered in 63% of patients who were evaluable at 12 mo. CONCLUSIONS:
      Oncologic and functional data from RARC remain immature, and longer-term
      prospective studies are needed. Cumulative analyses demonstrated that lymph node
      yields and PSM rates were similar between RARC and ORC. Conclusive long-term
      survival outcomes for RARC were limited, although oncologic outcomes up to 5 yr
      were similar to those reported for ORC. PATIENT SUMMARY: Although open radical
      cystectomy (RC) is still regarded as the standard treatment for muscle-invasive
      bladder cancer, laparoscopic and robot-assisted RCs are becoming more popular.
      Templates of lymph node dissection, lymph node yields, and positive surgical
      margin rates are acceptable with robot-assisted RC. Although definitive
      comparisons with open RC with respect to oncologic or functional outcomes are
      lacking, early results appear comparable.

PMID- 25560798
TI  - Systematic review and cumulative analysis of perioperative outcomes and
      complications after robot-assisted radical cystectomy.
AB  - CONTEXT: Although open radical cystectomy (ORC) is still the standard approach,
      laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy
      (RARC) have gained popularity. OBJECTIVE: To report a systematic literature
      review and cumulative analysis of perioperative outcomes and complications of
      RARC in comparison with ORC and LRC. EVIDENCE ACQUISITION: Medline, Scopus, and
      Web of Science databases were searched using a free-text protocol including the
      terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot*
      radical cystectomy. RARC case series and studies comparing RARC with either ORC
      or LRC were collected. Cumulative analysis was conducted. EVIDENCE SYNTHESIS: The
      searches retrieved 105 papers. According to the different diversion type, overall
      mean operative time ranged from 360 to 420 min. Similarly, mean blood loss ranged
      from 260 to 480 ml. Mean in-hospital stay was about 9 d for all diversion types,
      with consistently high readmission rates. In series reporting on RARC with either
      extracorporeal or intracorporeal conduit diversion, overall 90-d complication
      rates were 59% (high-grade complication: 15%). In series reporting RARC with
      intracorporeal continent diversion, the overall 30-d complication rate was 45.7%
      (high-grade complication: 28%). Reported mortality rates were <=3% for all
      diversion types. Comparing RARC and ORC, cumulative analyses demonstrated shorter
      operative time for ORC, whereas blood loss and in-hospital stay were better with
      RARC (all p values <0.003). Moreover, 90-d complication rates of any-grade and 90
      d grade 3 complication rates were lower for RARC (all p values <0.04), whereas
      high-grade complication and mortality rates were similar. CONCLUSIONS: RARC can
      be performed safely with acceptable perioperative outcome, although complications
      are common. Cumulative analyses demonstrated that operative time was shorter with
      ORC, whereas RARC may provide some advantages in terms of blood loss and
      transfusion rates and, more limitedly, for postoperative complication rates over
      ORC and LRC. PATIENT SUMMARY: Although open radical cystectomy (RC) is still
      regarded as a standard treatment for muscle-invasive bladder cancer, laparoscopic
      and robot-assisted RC are becoming more popular. Robotic RC can be safely
      performed with acceptably low risk of blood loss, transfusion, and intraoperative
      complications; however, as for open RC, the risk of postoperative complications
      is high, including a substantial risk of major complication and reoperation.

PMID- 25560799
TI  - An eleven gene molecular signature for extra-capsular spread in oral squamous
      cell carcinoma serves as a prognosticator of outcome in patients without nodal
      metastases.
AB  - OBJECTIVES: Extracapsular spread (ECS) is an important prognostic factor for oral
      squamous cell carcinoma (OSCC) and is used to guide management. In this study, we
      aimed to identify an expression profile signature for ECS in node-positive OSCC
      using data derived from two different sources: a cohort of OSCC patients from our
      institution (National Cancer Centre Singapore) and The Cancer Genome Atlas (TCGA)
      head and neck squamous cell carcinoma (HNSCC) cohort. We also sought to determine
      if this signature could serve as a prognostic factor in node negative cancers.
      MATERIALS AND METHODS: Patients with a histological diagnosis of OSCC were
      identified from an institutional database and fresh tumor samples were retrieved.
      RNA was extracted and gene expression profiling was performed using the
      Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. RNA sequence
      data and corresponding clinical data for the TCGA HNSCC cohort were downloaded
      from the TCGA Data Portal. All data analyses were conducted using R package and
      SPSS. RESULTS: We identified an 11 gene signature (GGH, MTFR1, CDKN3, PSRC1,
      SMIM3, CA9, IRX4, CPA3, ZSCAN16, CBX7 and ZFP3) which was robust in segregating
      tumors by ECS status. In node negative patients, patients harboring this ECS
      signature had a significantly worse overall survival (p=0.04). CONCLUSIONS: An
      eleven gene signature for ECS was derived. Our results also suggest that this
      signature is prognostic in a separate subset of patients with no nodal metastasis
      Further validation of this signature on other datasets and immunohistochemical
      studies are required to establish utility of this signature in stratifying early
      stage OSCC patients.

PMID- 25560800
TI  - Gene expression profiling reveals biological pathways responsible for phenotypic
      heterogeneity between UK and Sri Lankan oral squamous cell carcinomas.
AB  - OBJECTIVES: It is well recognized that oral squamous cell carcinoma (OSCC) cases
      from Asia that are associated with betel quid chewing are phenotypically distinct
      to those from Western countries that are predominantly caused by
      smoking/drinking, but the molecular basis of these differences are largely
      unknown. The aim of this study is to examine gene expression, related
      carcinogenic pathways and molecular processes that might be responsible for the
      phenotypic heterogeneity of OSCC between UK and Sri Lankan population groups.
      METHODS: We have compared the gene expression profiles of OSCCs and normal oral
      mucosal tissues from both Sri Lankan and UK individuals using Affymetrix gene
      expression arrays. The generated data was interrogated using significance
      analysis of microarrays and Ingenuity Pathway Analysis (IPA). RESULTS: The gene
      expression profiles of UK and Sri Lankan OSCC are similar in many respects to
      other oral cancer expression profiles reported in the literature and were mainly
      similar to each other. However, genes involved in tumor invasion, metastasis and
      recurrence were more obviously associated with UK tumors as opposed to those from
      Sri Lanka. CONCLUSION: The development of OSCCs in both UK and Sri Lankan
      populations appears largely mediated by similar biological pathways despite the
      differences related to race, ethnicity, lifestyle, and/or exposure to
      environmental carcinogens. However, IPA revealed a highly activated "Cell
      mediated Immune Response" in Sri Lankan normal and tumor samples relative to UK
      cohorts. It seems likely, therefore, that any future attempts to personalize
      treatment for OSCC patients will need to be different in Western and Asian
      countries to reflect differences in gene expression and the immune status of the
      patients.

PMID- 25560801
TI  - Application of neutrophil/lymphocyte ratio in predicting coronary blood flow and
      mortality in patients with ST-elevation myocardial infarction undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND: To investigate the potential correlation of neutrophil/lymphocyte
      ratio (NLR) to coronary blood flow and in-hospital along with long-term mortality
      in patients with ST-elevation myocardial infarction (STEMI) undergoing
      percutaneous coronary intervention (PCI). METHODS: In the current study, 636
      consecutive patients with STEMI were recruited and stratified into three tertiles
      by NLRs upon admission (tertile I<3.0, tertile II 3.0-6.40, tertile III>6.40).
      The coronary blood flow was expressed by corrected TIMI frame count (CTFC). The
      in-hospital mortality and 12-month long follow-up data were collected. Receiver
      operating characteristic (ROC) curves were also constructed. RESULTS: Our
      analysis demonstrated that NLR was positively correlated to CTFC and in-hospital
      mortality (r=0.517, p<0.001; r=0.439, p<0.001). In the multiple logistic
      regression analysis, NLR was testified as an independent risk factor for coronary
      blood flow after PCI and in-hospital mortality [odds ratio (OR)=2.031, 95%
      confidence interval (CI): 1.627-2.435, p<0.001; OR=1.176, 95% CI: 1.025-1.351,
      p=0.021]. During the 12-month follow-up, there were a total of 43 deaths and
      statistically significant increase in long-term mortality was observed in
      patients from tertile I to III (p=0.005). In the ROC curves analysis, the area
      under the curve (AUC=0.607, 95% CI: 0.475-0.739, p=0.253), with threshold value
      of 5.9 (sensitivity: 63.7%, specificity: 61.1%) for predicting in-hospital
      mortality. CONCLUSIONS: NLR, an indicator that can be tested in the laboratory
      with low cost and time consumption, is independently correlated to coronary blood
      flow and acts as an independent risk factor for in-hospital mortality in patients
      with STEMI undergoing PCI.

PMID- 25560802
TI  - Rutin potentially attenuates fluoride-induced oxidative stress-mediated
      cardiotoxicity, blood toxicity and dyslipidemia in rats.
AB  - This study was undertaken to evaluate cardio protective effect of rutin against
      sodium fluoride (NaF)-induced oxidative stress-mediated cardiotoxicity and blood
      toxicity. Cardiac injury was induced by daily administration of NaF 600 ppm in
      distilled water for four weeks. The animals exposed to NaF exhibited a
      significant increase in levels of cardiac serum markers, lipid peroxidative
      markers, serum total cholesterol, LDL, triglycerides and decrease in HDL levels.
      Decrease in hematological parameters, namely hemoglobin, red blood cells, mean
      corpuscular volume, mean corpuscular hemoglobin (MCH), MCH count and increase in
      white blood cells and erythrocyte sedimentation levels were also observed. Marked
      histopathological lesions and increased DNA fragmentation in cardiac tissues were
      observed. Activity of antioxidants-catalase, superoxide dismutase and reduced
      glutathione contents were decreased (p < 0.01), whereas lipid peroxidation
      product (malondialdehyde) was increased. A significant decrease in body and heart
      weight was also observed. Treatment with rutin effectively ameliorated the
      alterations in the studied parameters of rat through its antioxidant nature.
      There was also significant improvement in hematological parameters. Thus, results
      of this study clearly demonstrated that treatment with rutin against NaF
      intoxication has a significant role in protecting F-induced cardiotoxicity, blood
      toxicity and dyslipidemia in rats. 

PMID- 25560804
TI  - A TMC1 (transmembrane channel-like 1) mutation (p.S320R) in a Polish family with
      hearing impairment.
AB  - After excluding frequent mutations in common genes like GJB2, SLC26A4 and MT-RNR1
      by straightforward Sanger sequencing in about 20 Polish families with hearing
      impairment, new and possibly pathogenic mutations were searched for by next
      generation sequencing (NGS) screening using a specialised panel including more
      than 80 genes connected with hearing disorders. Due to high rates of false
      positive pathogen predictions for newly discovered single-nucleotide
      polymorphisms (SNPs), different prediction models were combined to enhance the
      prediction power. In one family with a record of over four generations, II,3 and
      II,4 were suspected of hearing impairment without medical records. A male person
      (III,2) displayed hearing loss of 40 dB hearing level (HL) and his two sons, IV,1
      and IV,2, were both affected; one with 90 dB HL and the other with 40 dB HL.
      Here, one heterozygous, non-synonymous variant was detected, with the SNP causing
      an amino acid substitution in TMC1 (transmembrane channel-like 1), a gene
      reported with many mutations in DFNA36 and DFNB7/11 (OMIM #606705 and #600974,
      respectively). Until now, the substitution p.S320R has not been described in any
      database. Instead of the significance of this mutation by bioinformatics tools,
      we confirmed the genotype-phenotype co-segregation in family members. The
      involvement of TMC1 in hereditary hearing impairment has not been observed in the
      Polish population so far.

PMID- 25560803
TI  - Improved knee extensor strength with resistance training associates with muscle
      specific miRNAs in older adults.
AB  - Regular exercise, particularly resistance training (RT), is the only therapy
      known to consistently improve muscle strength and quality (force per unit of
      mass) in older persons, but there is considerable variability in responsiveness
      to training. Identifying sensitive diagnostic biomarkers of responsiveness to RT
      may inform the design of a more efficient exercise regimen to improve muscle
      strength in older adults. MicroRNAs (miRNAs) are small non-coding RNAs that
      regulate gene expression. We quantified six muscle specific miRNAs (miR-1, -133a,
      -133b, -206, -208b and -499) in both muscle tissue and blood plasma, and their
      relationship with knee extensor strength in seven older (age=70.5 +/- 2.5 years)
      adults before and after 5 months of RT. MiRNAs differentially responded to RT;
      muscle miR-133b decreased, while all plasma miRNAs tended to increase. Percent
      changes in knee extensor strength with RT showed strong positive correlations
      with percent changes in muscle miR-133a, -133b, and -206 and with percent changes
      in plasma and plasma/muscle miR-499 ratio. Baseline level of plasma or
      plasma/muscle miR-499 ratio further predicts muscle response to RT, while changes
      in muscle miR-133a, -133b, and -206 may correlate with muscle TNNT1 gene
      alternative splicing in response to RT. Our results indicate that RT alters
      muscle specific miRNAs in muscle and plasma, and that these changes account for
      some of the variation in strength responses to RT in older adults.

PMID- 25560805
TI  - Delayed prelingual cochlear implantation in childhood and puberty.
AB  - OBJECTIVE: To evaluate the results of delayed cochlear impantion performed in
      childhood and puberty in the light of speech language pathology assessments.
      METHODS: Totally 49 children with prelingual profound hearing loss were included
      in the study. All children received a cochlear implant between the ages of 5 and
      19 years (Group 1 aged between 5 and 9 years, group 2 aged between 10 and 14
      years, group 3 aged between and 15 and 19 years). The MAIS, MUSS and PLS-4 scores
      of children were evaluated one month before, and one year and two years after the
      operation. The descriptive statistics included several independent variables; age
      of implantation; gender; trade name of the implant; preoperative duration of
      hearing aid use; preoperative special education, family support and additional
      handicap. These variables were categorical variables. We used repeated measures
      analysis of variance to test improvements in MAIS, MUSS and PLS scores, and
      whether this improvement depend on the independent variables. In addition, we
      also tested the interaction between time and the independent variables. RESULTS:
      The preoperative MAIS, MUSS and language scores were significantly higher in
      older children compared to younger children (p<0.01). After two years these
      scores were similar between the all age groups (p>0.4). There was a significant
      age and time interaction (p=0.005). That is, improvement continued in all age
      groups in a parallel way and group 2 reached to the level of group 1 after two
      years. However, group 3 almost reached to a plateau level after two years. The
      family support was associated with the MAIS, MUSS and language scores of the
      patients (p=0.01), and there was a family support-time interaction (p<0.0001). In
      group 1 and 2, the way of communication shifted from total communication (lip
      reading, sign language, auditory) to auditory-verbal communication in a
      significant number of the patients (p<0.01). However, that change in the way of
      communication was not statistically significant in group 3 (p>0.05). CONCLUSION:
      The decision of delayed cochlear implantation in children can be made in the
      light of following parameters. A good family support is most important. The
      patients must be wearing hearing aids regularly since early childhood, and
      preferably use the auditory verbal communication. Evaluation of the patient with
      MAIS, MUSS and PLS is important to understand the level of receptive and
      expressive communication level.

PMID- 25560807
TI  - Risk-reducing salpingectomy with delayed oophorectomy in BRCA1/2 mutation
      carriers: patients' and professionals' perspectives.
AB  - OBJECTIVE: To identify influencing factors of BRCA1/2 mutation carriers and their
      professionals for risk-reducing salpingectomy (RRS) with delayed oophorectomy
      (RRO) as a substitute for risk-reducing salpingo-oophorectomy (RRSO) and for
      study participation on this concept. METHODS: A qualitative study was performed
      by four focus group interviews with 39 BRCA1/2 mutation carriers and semi
      structured in-depth interviews with 23 professionals in the field of hereditary
      cancer. We used a theoretical framework of determinants of innovation within
      healthcare organizations to classify influencing factors (barriers and
      facilitators). RESULTS: Among BRCA1/2 mutation carriers, main barriers for RRS
      with delayed RRO were seriousness of ovarian cancer, family history, and previous
      breast cancer. Among professionals, delay of risk-reducing effect of oophorectomy
      on breast cancer risk and a second operation were recognized as main barriers.
      Both BRCA1/2 mutation carriers and professionals found uncertainty about the
      effect of RRS with delayed RRO and ease of the decision to undergo RRSO important
      barriers. The main facilitator mentioned by both was longer maintenance of
      ovarian function thereby delaying negative effects of early surgical menopause.
      For study participation, BRCA1/2 mutation carriers mentioned a randomized study
      design as the main barrier, whereas professionals identified two facilitators,
      namely willingness of BRCA1/2 mutation carriers for study participation and
      uniform counseling. Furthermore, most BRCA1/2 mutation carriers and professionals
      were willing to consider participation in a future non-randomized study.
      CONCLUSIONS: We identified several barriers and facilitators for RRS with delayed
      RRO, and for study participation which can be addressed to optimize the design
      and implementation of a non-randomized study.

PMID- 25560806
TI  - Pharmacologic inhibition of ATR and ATM offers clinically important distinctions
      to enhancing platinum or radiation response in ovarian, endometrial, and cervical
      cancer cells.
AB  - OBJECTIVE: Significant reductions in gynecologic (GYN) cancer mortality and
      morbidity require treatments that prevent and reverse resistance to chemotherapy
      and radiation. The objective of this study was to determine if pharmacologic
      inhibition of key DNA damage response kinases in GYN cancers would enhance cell
      killing by platinum-based chemotherapy and radiation. METHODS: A panel of human
      ovarian, endometrial and cervical cancer cell lines were treated with platinum
      drugs or ionizing radiation (IR) along with small molecule pharmacological kinase
      inhibitors of Ataxia telangiectasia mutated (ATM) and ATM and Rad-3-related
      (ATR). RESULTS: Pharmacologic inhibition of ATR significantly enhanced platinum
      drug response in all GYN cancer cell lines tested, whereas inhibition of ATM did
      not enhance the response to platinum drugs. Co-inhibition of ATM and ATR did not
      enhance platinum kill beyond that observed by inhibition of ATR alone. By
      contrast, inhibiting either ATR or ATM enhanced the response to IR in all GYN
      cancer cells, with further enhancement achieved with co-inhibition. CONCLUSIONS:
      These studies highlight actionable mechanisms operative in GYN cancer cells with
      potential to maximize response of platinum agents and radiation in newly
      diagnosed as well as recurrent gynecologic cancers.

PMID- 25560808
TI  - Serum human epididymal protein 4 (HE4) as biomarker for the differentiation
      between epithelial ovarian cancer and ovarian metastases of gastrointestinal
      origin.
AB  - OBJECTIVE: About 5-15% of all malignant ovarian tumors are metastases from other
      malignancies such as gastrointestinal tumors, breast cancer or melanoma. Also
      other gynecological tumors can metastasize to the ovaries. It is crucial to
      differentiate between primary epithelial ovarian cancer (EOC) and ovarian
      metastases because different treatment is required. The clinical value of human
      epididymal secretory protein 4 (HE4) as a serum biomarker in primary ovarian
      cancer has been established. The use of HE4 in the differentiation between
      primary ovarian cancer and ovarian metastases from other malignancies has never
      been investigated. METHODS: HE4, CA125 and CEA were measured in 192 patients with
      EOC (n=147) or ovarian metastases (n=40). Univariate and multivariate logistic
      regression analyses were done. Sensitivity, specificity and area under the curve
      (AUC) were calculated for all markers and ratios hereof using receiver operating
      characteristics methodology. RESULTS: Median serum HE4 concentration was
      significantly higher in patients with EOC compared to patients with ovarian
      metastases (431 pmol/L vs 68 pmol/L, p<0.001). HE4 and CEA were independent
      factors in differentiating between EOC and ovarian metastases (both p<0.001)
      while CA125 was not (p=0.33). The HE4(2.5)/CEA ratio demonstrated the highest
      discriminative value (ROC-AUC 0.94) compared to HE4, CEA, CA125 or CA125/CEA
      ratio (0.88, 0.78, 0.80 and 0.89 respectively) and showed a specificity of 82.5%
      at set sensitivity of 90% in discriminating EOC from ovarian metastases.
      CONCLUSION: HE4 can be used in combination with CEA to make the distinction
      between EOC and ovarian metastases from gastrointestinal origin.

PMID- 25560809
TI  - Effect of surgical approach on erectile function recovery following bilateral
      nerve-sparing radical prostatectomy: an evaluation utilising data from a
      randomised, double-blind, double-dummy multicentre trial of tadalafil vs placebo.
AB  - OBJECTIVES: To report pre-specified and exploratory results on the effect of
      different surgical approaches on erectile function (EF) after nerve-sparing
      radical prostatectomy (nsRP) obtained from the multicentre, randomised, double
      blind, double-dummy REACTT trial of tadalafil (once a day [OaD] or on-demand [pro
      re-nata, PRN]) vs placebo. PATIENTS AND METHODS: Patients aged <68 years with
      normal preoperative EF who underwent nsRP for localised prostate cancer (Gleason
      <=7, prostate-specific antigen [PSA] <10 ng/mL) were randomised after nsRP 1:1:1
      to 9-month double-blind treatment with tadalafil 5 mg OaD, tadalafil 20 mg PRN,
      or placebo, followed by 6-week drug-free washout, and 3-month open-label OaD
      treatment (all patients). Recovery of EF was defined as an International Index of
      Erectile Function (IIEF)-EF domain score of >=22 and normal orgasmic function was
      defined based on IIEF Question 10. Both parameters were analysed at the end of
      washout using logistic regression including terms for treatment, country, visit,
      visit-by-treatment interaction, age group, nerve-sparing score (perfect = 2, non
      perfect >2), and surgical approach (open surgery, robot-assisted laparoscopy,
      conventional laparoscopy, other). Time to EF recovery was analysed post hoc with
      a Cox proportional-hazards model including terms for treatment, age-group,
      country, surgical approach and surgery-by-treatment interaction. RESULTS: Of 422
      patients treated, 189 underwent open surgery, 115 robot-assisted laparoscopy, 88
      conventional laparoscopy and 30 surgery classified as 'other'. The odds of
      achieving EF recovery at the end of drug-free washout were about twice as high
      for the robot-assisted laparoscopy group compared with the open surgery group
      (odds ratio 2.42; 95% confidence interval [CI] 1.24, 4.72; P = 0.029). Patients
      who underwent robot-assisted laparoscopy were significantly more likely to
      recover during double-blind treatment compared with patients who underwent open
      surgery (hazard ratio 1.92; 95% CI 1.17, 3.15; P = 0.010). No favourable effect
      of conventional laparoscopy compared with open surgery could be seen. CONCLUSION:
      These results may provide further insights into the role of surgery on EF
      recovery after nsRP. However, the trial was not designed for these analyses and
      further prospective studies are needed.

PMID- 25560810
TI  - Cross-sectional associations between different measures of obesity and muscle
      strength in men and women in a British cohort study.
AB  - OBJECTIVES: The relationship between obesity and grip strength, a key indicator
      of sarcopenia, has been inconsistently reported. We aimed to examine associations
      between grip strength and both body mass index (BMI), a clinical indicator of
      total adiposity, and waist circumference (WC), an indicator of central adiposity.
      DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Data collected from
      8,441 men and women, aged 48-92 years old, who attended the third health
      examination of the European Prospective Investigation into Cancer-Norfolk study
      was used. MEASUREMENTS: Maximum grip strength (Smedley dynamometer), BMI
      (weight/height2) and WC (measured at the natural waist) were ascertained at a
      research clinic. The associations between grip strength and adiposity measures
      were explored using linear regression with adjustment for age, height, social
      class, physical activity, prevalent disease, smoking status and alcohol intake.
      RESULTS: Men and women were examined separately and those in the upper quartile
      of BMI were 2.70kg (95%CI 2.07, 3.33) and 1.46kg (95%CI 1.05, 1.86) stronger
      respectively than those in the bottom quartile (P trends <0.001). Grip strength
      also increased weakly with increasing WC. However, including both BMI and WC in
      the same regression model revealed an inverse association between grip strength
      and WC, whilst the previously observed association with BMI strengthened. For
      every 10cm increase in WC, grip strength was 3.56kg (95%CI 3.04, 4.08) lower in
      men and 1.00kg (95%CI 0.74, 1.24) lower in women. CONCLUSIONS: Larger overall
      body mass, indicated by higher BMI, is associated with stronger grip strength but
      high WC, a clinical indicator of central obesity, is associated with lower grip
      strength. Abdominal fat is the most metabolically active adipose tissue and this
      provides a clue to potential mechanisms underlying relationships between fat and
      skeletal muscle. Additionally, it reinforces the recommendation to measure WC in
      clinical practice, especially when BMI is below obese ranges.

PMID- 25560812
TI  - Obese very old women have low relative hangrip strength, poor physical function,
      and difficulties in daily living.
AB  - OBJECTIVES: To investigate whether anthropometric and body composition variables
      and handgrip strength (HS) were associated with physical function and independent
      daily living in 88-year-old Swedish women. PARTICIPANTS: A cross-sectional
      analysis of 83 community-dwelling women aged 88 years who were of normal weight
      (n=30), overweight (n=29), and obese (n=24) was performed. MEASUREMENTS: Body
      weight (Wt), height, waist circumference (WC), and arm circumference were
      assessed using an electronic scale and a measuring tape. Tricep skinfold
      thickness was measured using a skinfold calliper. Fat mass (FM) and fat-free mass
      (FFM) were measured using bioelectrical impedance analysis, and HS was recorded
      with an electronic grip force instrument. Linear regression was used to determine
      the contributions of parameters as a single predictor or as a ratio of HS to
      physical function (Short Form-36, SF-36PF) and instrumental activities of daily
      living (IADL). RESULTS: Obese women had greater absolute FM and FFM and lower HS
      corrected for FFM and HS-based ratios (i.e., HS/Wt, HS/body mass index [BMI])
      than their normal weight and overweight counterparts. After adjusting for
      physical activity levels and the number of chronic diseases, HS-based ratios
      explained more variance in SF-36PF scoring (R2, 0.52-0.54) than single
      anthropometric and body composition variables (R2, 0.45-0.51). WC, HS, and HS
      based ratios (HS/Wt and HS/FFM) were also associated with independence in IADL.
      CONCLUSION: Obese very old women have a high WC but their HS is relatively low in
      relation to their Wt and FFM. These parameters are better than BMI for predicting
      physical function and independent daily living.

PMID- 25560811
TI  - Dietary mineral intakes of rural midlife to older adult women with
      prehypertension in Midwestern United States.
AB  - OBJECTIVES: Midlife to older rural women with prehypertension are at increased
      risk for hypertension and its impact on cardiovascular health with advancing age.
      Because modification of dietary factors could help alleviate risk, the objective
      of this study was to explore calcium, magnesium, potassium and sodium intakes of
      midlife to older rural women, with identification of their top food sources.
      DESIGN: Survey of baseline dietary intake data of women and comparison to
      standard recommendations. SETTING: Rural Midwestern United States. PARTICIPANTS:
      289 rural women, age 40-69, with prehypertension who volunteered for lifestyle
      modification to reduce blood pressure. MEASUREMENTS: Baseline nutrition data
      using the Block Health Habit and History Questionnaire were collected over a
      twelve-month rolling enrollment period from rural women with prehypertension.
      Mineral intakes were calculated and compared to recommended standards. Top ten
      foods contributing to each mineral were identified. RESULTS: The percent of women
      who met the Recommended Dietary Allowance (RDA)/Adequate Intake (AI)
      recommendations for their age groups ranged from a high 42.9% for magnesium to a
      low of 4.2% for potassium. Mean intakes of calcium, magnesium and potassium were
      all below recommended levels and sodium intakes were above recommendation.
      CONCLUSION: Midlife to older rural US women with prehypertension were eating some
      of the foods that would help them meet mineral recommendations. As a preventive
      approach to reducing hypertension risk, clinical practice could include advising
      on ways to increase both commonly and less commonly consumed nutrient-rich foods
      with awareness of what is typically available in the rural area.

PMID- 25560813
TI  - Nutritional status of an elderly population in Southwest China: a cross-sectional
      study based on comprehensive geriatric assessment.
AB  - OBJECTIVE: Few data is available on the nutritional status of old Chinese. The
      present study aimed to describe the nutritional status and clinical correlates
      for malnutrition risk in the older people. DESIGN: Cross-sectional study.
      SETTING: Hospital- and community-based older people were recruited in the region
      of Chongqing, China. PARTICIPANTS: 558 individuals aged 60 years old or over
      between April 2011 and October 2012. MEASUREMENTS: Comprehensive geriatric
      assessment was performed and nutritional status was assessed by the Mini
      Nutritional Assessment Short Form (MNA-SF). Nutrition-associated factors were
      analyzed, including health status (chronic diseases, depression, cognition,
      function impaired), social factors (education status, marital status, the type of
      work before 60 years old) and life style factors (smoking, drinking, diet).
      RESULTS: The mean age was 73.1+/-8.0 years and 43.9% were men. Prevalence of
      malnutrition and risk for malnutrition were 3.2% and 19.3 %, respectively.
      Several factors increased poor nutrition independently including self-rated
      health, comorbidity, chronic obstructive pulmonary disease, gastrointestinal
      disease and cognitive impairment. Fish decreased the risk of poor nutrition.
      CONCLUSIONS: The prevalence was relatively low in older people of Chongqing,
      Southwest China. Poor nutrition was found to be increased due to the common
      health problems. Thus the patients with these problems should pay more attention
      on nutritional status. The older people should often have fish because of their
      nutritional benefit.

PMID- 25560814
TI  - Cognitive function in a middle aged cohort is related to higher quality dietary
      pattern 5 and 25 years earlier: the CARDIA study.
AB  - BACKGROUND: Preserving cognitive function is an important public health issue. We
      investigated whether dietary pattern associates with cognitive function in middle
      age. METHODS: We studied 2435 participants in the community-based Coronary Artery
      Risk Development in Young Adults (CARDIA) study of black and white men and women
      aged 18-30 in 1985-86 (year 0, Y0). We hypothesized that a higher A Priori Diet
      Quality Score, measured at Y0 and Y20, is associated with better cognitive
      function measured at Y25. The diet score incorporated 46 food groups (each in
      servings/day) as the sum of quintile ranks of food groups rated beneficial, 0 for
      food groups rated neutral, and reversed quintile ranks for food groups rated
      adverse; higher score indicated better diet quality. Y25 cognitive testing
      included verbal memory (Rey Auditory-Verbal Learning Test (RAVLT)), psychomotor
      speed (Digit Symbol Substitution Test (DSST)) and executive function (Stroop).
      RESULTS: Per 10-unit higher diet score at Y20, the RAVLT was 0.32 words recalled
      higher, the DSST was 1.76 digits higher, and the Stroop was 1.00 seconds+errors
      lower (better performance) after adjusting for race, sex, age, clinic, and energy
      intake. Further adjustment for physical activity, smoking, education, and body
      mass index attenuated the association slightly. Diet score at Y0 and increase in
      diet score over 20 years were also positively associated with each cognitive
      test. CONCLUSIONS: A higher quality dietary pattern was associated with better
      cognitive function 5 years and even 25 years later in apparently healthy middle
      aged adults.

PMID- 25560815
TI  - Nutrient biomarkers and vascular risk factors in subtypes of mild cognitive
      impairment: a cross-sectional study.
AB  - OBJECTIVE: To investigate the interrelationships among blood nutrient biomarkers,
      the Framingham Stroke Risk Profile (FSRP), and cognitive impairment features in
      mild cognitive impairment (MCI) subjects and to verify whether nutrient
      biomarkers and FSRP are risk factors for MCI. METHODS: According to the criteria
      for MCI developed by Petersen, 81 subjects aged 50-80 years were divided into a
      normal control group (NC group, n = 36) and an MCI group (n = 45). Then, the MCI
      group was divided into an amnestic MCI (a-MCI) and a multidomain MCI (md-MCI)
      group. All subjects were administered a comprehensive health history to calculate
      their FSRP score and a thorough neuropsychological assessment of four cognitive
      domains. Blood samples from all subjects were collected to measure the nutrient
      biomarkers. RESULTS: FSRP score was not only associated with memory function, but
      also with executive function, which itself had a negative relationship with
      eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total n-3
      polyunsaturated fatty acids (n-3PUFAs) levels, and a positive relationship with
      the ratio of n-6 PUFAs to n-3 PUFAs(n6/n3). Compared with the NC group, the
      concentrations of EPA, DHA, 25-hydroxy vitamin D (25OHD), and folate and the
      ratio of n3/n6 in the md-MCI group were significantly lower. In the a-MCI group,
      only DHA concentrations and the ratio of n3/n6 were significantly lower. After
      adjustment for potential confounding variables, low education level [Adjusted
      OR=8.71 (95%CI: 1.83-41.50), p trend = 0.007], decreased plasma 25OHD [Adjusted
      OR = 4.41 (95% CI: 1.08-17.94), p trend=0.04] and decreased plasma DHA [Adjusted
      OR = 6.69 (95% CI: 1.37-32.72), p = 0.02] were associated with a higher risk of
      MCI. CONCLUSIONS: Several nutrient biomarkers in MCI patients, especially in md
      MCI patients, were lower compared with healthy controls, suggesting that lower
      25OHD and DHA levels are risk factors for MCI. However, we found no evidence that
      FSRP is an early biomarker of MCI.

PMID- 25560816
TI  - Cognitive impairment, genomic instability and trace elements.
AB  - Cognitive impairments are often related to aging and micronutrient deficiencies.
      Various essential micronutrients in the diet are involved in age-altered
      biological functions such as, zinc, copper, iron, and selenium that play pivotal
      roles either in maintaining and reinforcing the antioxidant performances or in
      affecting the complex network of genes (nutrigenomic approach) involved in
      encoding proteins for biological functions. Genomic stability is one of the
      leading causes of cognitive decline and deficiencies or excess in trace elements
      are two of the factors relating to it. In this review, we report and discuss the
      role of micronutrients in cognitive impairment in relation to genomic stability
      in an aging population. Telomere integrity will also be discussed in relation to
      aging and cognitive impairment, as well as, the micronutrients related to these
      events. This review will provide an understanding on how these three aspects can
      relate with each other and why it is important to keep a homeostasis of
      micronutrients in relation to healthy aging. Micronutrient deficiencies and aging
      process can lead to genomic instability. 

PMID- 25560817
TI  - Brain metabolism and Alzheimer's disease: the prospect of a metabolite-based
      therapy.
AB  - The brain is one of the most energy-demanding organs in the body. It has evolved
      intricate metabolic networks to fulfill this need and utilizes a variety of
      substrates to generate ATP, the universal energy currency. Any disruption in the
      supply of energy results in various abnormalities including Alzheimer's disease
      (AD), a condition with markedly diminished cognitive ability. Astrocytes are an
      important participant in maintaining the cerebral ATP budget. However, under
      oxidative stress induced by numerous factors including aluminum toxicity, the
      ability of astroctyes to generate ATP is impaired due to dysfunctional
      mitochondria. This leads to globular, glycolytic, lipogenic and ATP-deficient
      astrocytes, cerebral characteristics common in AD patients. The reversal of these
      perturbations by such natural metabolites as pyruvate, alpha-ketoglutarate,
      acetoacetate and L-carnitine provides valuable therapeutic cues against AD. 

PMID- 25560818
TI  - Exploratory analysis of dietary intake and brain iron accumulation detected using
      magnetic resonance imaging in older individuals: the Lothian Birth Cohort 1936.
AB  - CONTEXT: Brain Iron Deposits (IDs) are associated with neurodegenerative diseases
      and impaired cognitive function in later life, but their cause is unknown. Animal
      studies have found evidence of relationships between dietary iron, calorie and
      cholesterol intake and brain iron accumulation. OBJECTIVES: To investigate the
      relationship between iron, calorie, and cholesterol intake, blood indicators of
      iron status, and brain IDs in humans. DESIGN, SETTING AND PARTICIPANTS: Cohort of
      1063 community-dwelling older individuals born in 1936 (mean age 72.7years,
      SD=0.7) with dietary information, results from blood sample analyses and brain
      imaging data contemporaneously in old age. MEASUREMENTS: Magnetic Resonance
      Imaging was used to assess regional volumes of brain IDs in basal ganglia,
      brainstem, white matter, thalamus, and cortex/border with the corticomedullary
      junction, using a fully automatic assessment procedure followed by individual
      checking/correction where necessary. Haemoglobin, red cell count, haematocrit,
      mean cell volume, ferritin and transferrin were obtained from blood samples and
      typical daily intake of iron, calories, and cholesterol were calculated from a
      validated food-frequency questionnaire. RESULTS: Overall, 72.8% of the sample
      that had valid MRI (n=676) had brain IDs. The median total volume of IDs was
      40mm3, inter-quartile range (IQR)=196. Basal ganglia IDs (median=35, IQR=159.5
      mm3), were found in 70.6% of the sample. IDs in the brainstem were found in 12.9%
      of the sample, in the cortex in 1.9%, in the white matter in 6.1% and in the
      thalamus in 1.0%. The median daily intake of calories was 1808.5kcal (IQR=738.5),
      of cholesterol was 258.5mg (IQR=126.2) and of total iron was 11.7mg (IQR=5).
      Iron, calorie or cholesterol intake were not directly associated with brain IDs.
      However, caloric intake was associated with ferritin, an iron storage protein
      (p=0.01). CONCLUSION: Our results suggest that overall caloric, iron and
      cholesterol intake are not associated with IDs in brains of healthy older
      individuals but caloric intake could be associated with iron storage. Further
      work is required to corroborate our findings on other samples and investigate the
      underlying mechanisms of brain iron accumulation.

PMID- 25560819
TI  - Strategies to implement community guidelines on nutrition and their long-term
      clinical effects in nursing home residents.
AB  - OBJECTIVES: Studies on implementation techniques that focus on nutrition in the
      setting of elderly care are scarce. The aims of this study were to compare two
      implementation strategies i.e., external facilitation (EF) and educational
      outreach visits (EOVs), in order to introduce nutritional guidelines (e.g.
      screening, food quality and mealtime ambience), into a nursing home (NH) setting
      and to evaluate the clinical outcomes. DESIGN: A controlled study with baseline
      and follow-up measurements. SETTING: Four NHs. PARTICIPANTS: A total of 101 NH
      residents. INTERVENTION: The EF was a one-year, multifaceted intervention that
      included support, guidance, practice audits, and feedback that were provided to
      two NHs. The EOVs performed at the other NHs consisted of one session of three
      hours of lectures about the guidelines. Both interventions targeted a team of the
      unit manager, the head nurse, and 5-10 of the care staff. MEASUREMENTS: The
      outcomes were nutritional status (Mini Nutritional Assessment-Short Form, MNA
      SF), body mass index (BMI), functional ability (Barthel Index, BI), cognitive
      function (Short Portable Mental Status Questionnaire, SPMSQ, performed in a
      subgroup of communicative NH residents), health-related quality of life (EQ-5D),
      and the levels of certain biochemical markers like for example vitamin D, albumin
      and insulin-like growth factor 1. RESULTS: After a median of 18 months,
      nutritional parameters (MNA-SF and BMI) remained unchanged in both groups. While
      there were no differences in most outcomes between the two groups, the cognitive
      ability of those in the EOV group deteriorated more than in individuals in the EF
      group (p=0.008). Multiple linear regression analyses indicated that the
      intervention group assignment (EF) was independently from other potentially
      related factors associated with less cognitive decline. CONCLUSION: An extended
      model of implementation of nutritional guidelines, including guidance and
      feedback to NH staff, did not affect nutritional status but may be associated
      with a delayed cognitive decline in communicative NH residents.

PMID- 25560820
TI  - Twelve-month consumption of a polyphenol extract from olive (Olea europaea) in a
      double blind, randomized trial increases serum total osteocalcin levels and
      improves serum lipid profiles in postmenopausal women with osteopenia.
AB  - OBJECTIVES: Osteoporosis is a skeletal disorder characterized by impaired bone
      turnover and compromised bone strength, thereby predisposing to increased risk of
      fracture. Preclinical research has shown that compounds produced by the olive
      tree (Olea europaea), may protect from bone loss, by increasing osteoblast
      activity at the expense of adipocyte formation. The aim of this exploratory study
      was to obtain a first insight on the effect of intake of an olive extract on bone
      turnover in postmenopausal women with decreased bone mass (osteopenia). DESIGN
      AND SETTING: For that, a double blind, placebo-controlled study was performed in
      which participants were randomly allocated to either treatment or placebo groups.
      PARTICIPANTS: 64 osteopenic patients, with a mean bone mineral density (BMD) T
      score between -1.5 and -2.5 in the lumbar spine (L2-L4) were included in the
      study. INTERVENTION AND MEASUREMENTS: PARTICIPANTS received for 12 months daily
      either 250 mg/day of olive extract and 1000 mg Ca (treatment) or 1000 mg Ca alone
      (placebo). Primary endpoints consisted of evaluation of bone turnover markers.
      Secondary endpoints included BMD measurements and blood lipid profiles. RESULTS:
      After 12 months, the levels of the pro-osteoblastic marker osteocalcin were found
      to significantly increase in the treatment group as compared to placebo.
      Simultaneously, BMD decreased in the placebo group, while remaining stable in the
      treatment group. In addition, improved lipid profiles were observed, with
      significant decrease in total- and LDL-cholesterol in the treatment group.
      CONCLUSION: This exploratory study supports preclinical observations and warrants
      further research by showing that a specific olive polyphenol extract
      (Bonolive(r)) affects serum osteocalcin levels and may stabilize lumbar spine
      BMD. Moreover, the improved blood lipid profiles suggest additional health
      benefits associated to the intake of the olive polyphenol extract.

PMID- 25560822
TI  - Weight loss, mortality and associated potentially modifiable nutritional risk
      factors among nursing home residents--a Danish follow-up study.
AB  - OBJECTIVE: The objective of this follow-up study is to assess the association
      between different potentially modifiable nutritional risk factors; weight loss
      after six and 12 months and mortality. DESIGN, SETTING: A one year follow-up
      project among Danish nursing home residents. PARTICIPANTS: A total of 441 nursing
      home resident living in 11 nursing homes. MEASUREMENTS: Odds ratio was calculated
      and used to assess the strength of association between different potentially
      modifiable nutritional risk factors and nutritional status of the participants.
      The difference in mortality between those who died versus survivors was assessed
      by means of Fishers Exact Test. RESULTS: Almost half experienced a loss of weight
      during the follow-up period. The nutritional risk factors significantly or
      borderline significantly associated with weight loss were; eating dependency,
      leaves 25% or more of food uneaten at most meals, chewing and swallowing
      problems. The prevalence of eating dependency; leaves 25% or more of food uneaten
      at most meals; swallowing problems and enteral nutrition were higher among those
      who died than among survivors. CONCLUSION: A high percentage of old nursing home
      residents suffer from weight loss and this is associated with several potentially
      modifiable nutritional risk factors. Increased combined efforts from all levels
      of care and wider ranged multidisciplinary nutritional support need to be
      implemented. Regular routines for assessing weight loss and the potentially
      modifiable nutritional risk factors cannot be stressed enough.

PMID- 25560821
TI  - Effect of protein source during weight loss on body composition, cardiometabolic
      risk and physical performance in abdominally obese, older adults: a pilot feeding
      study.
AB  - OBJECTIVES: The purpose of this pilot study was to begin to examine the effect of
      dietary protein source (soy protein versus non-soy protein) during weight loss on
      body composition, and cardiometabolic and functional decline risk factors in
      older, abdominally obese adults. DESIGN: Two-arm, single-blind, randomized,
      controlled trial. SETTING: Wake Forest School of Medicine, Winston-Salem NC
      27157, USA. PARTICIPANTS: 25 older (68.4+/-5.5 years, 88% female), abdominally
      obese (BMI: 35.1+/-4.3 kg/m2; WC: 101.4+/-13.1 cm) men and women were randomized
      to participate in the study. INTERVENTION: A 12-week weight loss intervention,
      with participants randomized to consume soy protein-based meal replacements (S;
      n=12) or non-soy protein-based meal replacements (NS; n=12), in addition to
      prepared meals, and all participants targeted to receive an individualized
      caloric deficit of 500 kcal/day. MEASUREMENTS: Body weight and composition
      (assessed via DXA and CT), conventional biomarkers of cardiometabolic risk, and
      physical performance measures were assessed pre- and post-intervention.
      Additional endpoints of feasibility (accrual, participation, retention,
      compliance, and safety) are reported. RESULTS: A total of 24 participants (87%
      female) completed the study (96% retention) and lost an average of 7.8+/-3.0 kg
      over the 12-week period, with no difference seen between groups (p=0.83).
      Although nearly all measures of global and regional body composition were
      significantly reduced following the 12-week intervention, differences were not
      observed between groups. Among cardiometabolic risk factors and physical
      performance measures, only diastolic blood pressure was significantly lower in
      the NS group compared to the S group (66.7+/-2.7 mmHg vs 73.5+/-2.7 mmHg,
      respectively; p=0.04). Interestingly, in groups combined, despite significant
      reductions in body weight and lean mass, no significant changes in 400-meter walk
      time (+5.3+/-43.4 s), short physical performance battery score (+0.1+/-1.0), grip
      strength (-0.3+/-3.2 kg), or relative knee extensor strength (-0.0+/-0.0 N/m/cm3
      thigh muscle volume) were observed. CONCLUSIONS: Data presented here suggest that
      a 12-week weight loss intervention, which incorporates S and NS meal replacement
      products, is associated with clinically significant weight loss and improvements
      in several parameters of cardiometabolic risk and unchanged physical function and
      strength. RESULTS do not differ by protein source and suggest that soy protein is
      at least as good as other protein sources for weight loss during low-calorie
      dietary interventions in older adults.

PMID- 25560823
TI  - Evaluating the effectiveness of implementing quality management practices in the
      medical industry.
AB  - OBJECTIVE: To discuss the effectiveness of 30 quality management practices (QMP)
      including Strategic Management, Balanced ScoreCard, Knowledge Management, and
      Total Quality Management in the medical industry. DESIGN: A V-shaped performance
      evaluation matrix is applied to identify the top ten practices that are important
      but not easy to use or implement. Quality Function Deployment (QFD) is then
      utilized to find key factors to improve the implementation of the top ten tools.
      SETTING AND PARTICIPANTS: The questionnaires were sent to the nursing staff and
      administrators in a hospital through e-mail and posts. A total of 250 copies were
      distributed and 217 copies were valid. MEASUREMENTS: The importance, easiness,
      and achievement (i.e., implementation level) of 30 quality management practices
      were used. RESULTS: Key factors for QMP implementation were sequenced in order of
      importance as top management involvement, inter-department communication and
      coordination, teamwork, hospital-wide participation, education and training,
      consultant professionalism, continuous internal auditing, computerized process,
      and incentive compensation. CONCLUSIONS: Top management can implement the V
      shaped performance matrix to determine whether quality management practices need
      improvement and if so, utilize QFD to find the key factors for improvement.

PMID- 25560825
TI  - How will I be remembered? Conserving the environment for the sake of one's
      legacy.
AB  - Long time horizons and social distance are viewed as key psychological barriers
      to proenvironmental action, particularly regarding climate change. We suggest
      that these challenges can be turned into opportunities by making salient long
      term goals and motives, thus shifting preferences between the present self and
      future others. We tested whether individuals' motivation to leave a positive
      legacy can be leveraged to increase engagement with climate change and other
      environmental problems. In a pilot study, we found that individual differences in
      legacy motivation were positively associated with proenvironmental behaviors and
      intentions. In a subsequent experiment, we demonstrated that priming legacy
      motives increased donations to an environmental charity, proenvironmental
      intentions, and climate-change beliefs. Domain-general legacy motives represent a
      previously understudied and powerful mechanism for promoting proenvironmental
      behavior.

PMID- 25560824
TI  - Community-dwelling female fallers have lower muscle density in their lower legs
      than non-fallers: evidence from the Saskatoon Canadian Multicentre Osteoporosis
      Study (CaMos) cohort.
AB  - OBJECTIVES: Our objectives were to determine whether peripheral quantitative
      computed tomography (pQCT)-derived lower leg muscle density and area, and basic
      functional mobility differ between community-dwelling older women who do and do
      not report recent falls. DESIGN: Matched case-control comparison. SETTING:
      Academic biomedical imaging laboratory. PARTICIPANTS: 147 Women, 60 years or
      older (mean age 74.3 y, SD 7.7) recruited from a longitudinal, population-based
      cohort representing community-dwelling residents in the area of Saskatoon,
      Canada. MEASUREMENTS: A cross-sectional pQCT scan of the non-dominant lower leg
      was acquired to determine muscle density and area. Basic functional mobility
      (Timed Up and Go Test [TUG]) and SF36 health status were also measured. Fallers
      (one or more falls) and non-fallers (no falls) were grouped according to a 12
      month retrospective survey and matched on measured covariates. RESULTS: The
      muscle density of fallers (n = 35) was a median of 2.1 mg/cm3 lower (P = 0.019,
      95% C.I. -3.9 to -0.1) than non-fallers (n = 78) after matching and adjusting for
      age, body mass index, and SF36 general health scores. Muscle area and TUG did not
      differ between fallers and non-fallers. CONCLUSIONS: Muscle density may serve as
      a physiological marker in the assessment of lower leg muscular health and fall
      risk in community-dwelling elderly women. These results are limited to our study
      population who were mostly Caucasian. Prospective studies are required for
      verification.

PMID- 25560827
TI  - Duty hours as viewed through a professionalism lens.
AB  - Understanding medical professionalism and its evaluation is essential to ensuring
      that physicians graduate with the requisite knowledge and skills in this domain.
      It is important to consider the context in which behaviours occur, along with
      tensions between competing values and the individual's approach to resolving such
      conflicts. However, too much emphasis on behaviours can be misleading, as they
      may not reflect underlying attitudes or professionalism in general. The same
      behaviour can be viewed and evaluated quite differently, depending on the
      situation. These concepts are explored and illustrated in this paper in the
      context of duty hour regulations. The regulation of duty hours creates many
      conflicts that must be resolved, and yet their resolution is often hidden,
      especially when compliance with or violation of regulations carries significant
      consequences. This article challenges attending physicians and the medical
      education community to reflect on what we value in our trainees and the
      attributions we make regarding their behaviours. To fully support our trainees'
      development as professionals, we must create opportunities to teach them the
      valuable skills they will need to achieve balance in their lives.
      [P]rofessionalism has no meaningful existence independent of the interactions
      that give it form and meaning. There is great folly in thinking otherwise.
      Hafferty and Levinson (2008)[1] Understanding and evaluating professionalism is
      essential to excellence in medical education and is mandated by organizations
      that oversee medical training [2]. Historically, attention has been focused
      largely on the professionalism of individual students or residents, at least for
      the purposes of evaluation. Yet there is now a growing appreciation that
      professionalism can be defined, understood, and evaluated from multiple
      perspectives [3]. Importantly, context has been recognized as critical to shaping
      trainees' behaviours, and hence as important to our understanding of them [4]. A
      restriction in duty hours for trainees is clearly an important environmental and
      contextual factor to consider in evaluating professional behaviour. In this paper
      I will review some key issues with respect to understanding and evaluating
      professionalism, and then discuss these in the context of duty hour reform.
      Readers should note that this is not intended to be a comprehensive review of the
      literature of either professionalism or duty hour reform, but rather a critical
      narrative review that uses selected articles.

PMID- 25560828
TI  - The protective effect of FGF21 on diabetes-induced male germ cell apoptosis is
      associated with up-regulated testicular AKT and AMPK/Sirt1/PGC-1alpha signaling.
AB  - Fibroblast growth factor 21 (FGF21) is a metabolic regulator that is required for
      normal spermatogenesis and protects against diabetes-induced germ cell apoptosis.
      Here, we tried to define whether diabetes-induced germ cell apoptosis that is
      predominantly due to increased oxidative stress was associated with impaired
      glucose and fatty acid metabolism, by examining the effects of Fgf21 gene
      knockout (FGF21-KO) or FGF21 treatment on the glucose and fatty acid metabolic
      pathways in streptozotocin-induced diabetic mice. Western blottings revealed that
      protein kinase B (AKT)-mediated glucose signaling was down-regulated in diabetic
      testes and further decreased in FGF21-KO diabetic group both 10 days and 2 months
      after diabetes onset, reflected by reduced glycogen synthase (GS) kinase (GSK)
      3beta phosphorylation and increased GS phosphorylation. Deletion of the Fgf21
      gene also inactivated fatty acid metabolism-related factors, AMP-activated
      protein kinase (AMPK), sirtuin 1 (Sirt1), and peroxisome proliferator-activated
      receptor-gamma coactivator 1alpha (PGC-1alpha), along with exacerbating diabetes
      induced testicular oxidative stress and damage. Treatment with recombinant FGF21
      partially prevented these diabetic effects. In FGF21-KO nondiabetic mice,
      testicular AMPK/Sirt1/PGC-1alpha signaling was down-regulated and AKT1 and murine
      double minute 2 were inactivated along with the increased p53 expression but not
      AKT2, GSK-3beta, and GS. These results suggest that the role of FGF21 in
      maintaining spermatogenesis is associated with its activation of AKT1 and
      inhibition of p53. Deletion of the Fgf21gene significantly exacerbates diabetes
      induced down-regulation of testicular AKT/GSK-3beta/GS and AMPK/Sirt1/PGC-1alpha
      pathways and testicular oxidative stress and cell apoptosis.

PMID- 25560829
TI  - ROR inverse agonist suppresses insulitis and prevents hyperglycemia in a mouse
      model of type 1 diabetes.
AB  - Hyperglycemia associated with type 1 diabetes is a consequence of immune-mediated
      destruction of insulin producing pancreatic beta-cells. Although it is apparent
      that both CD8(+) T cells and TH1 cells are key contributors to type 1 diabetes,
      the function of TH17 cells in disease onset and progression remains unclear. The
      nuclear receptors retinoic acid receptor-related orphan receptors-alpha and
      gammat (RORalpha and RORgammat) play critical roles in the development of TH17
      cells and ROR-specific synthetic ligands have proven efficacy in several mouse
      models of autoimmunity. To investigate the roles and therapeutic potential for
      targeting the RORs in type 1 diabetes, we administered SR1001, a selective
      RORalpha/gamma inverse agonist, to nonobese diabetic mice. SR1001 significantly
      reduced diabetes incidence and insulitis in the treated mice. Furthermore, SR1001
      reduced proinflammatory cytokine expression, particularly TH17-mediated
      cytokines, reduced autoantibody production, and increased the frequency of
      CD4(+)Foxp3(+) T regulatory cells. These data suggest that TH17 cells may have a
      pathological role in the development of type 1 diabetes, and use of ROR-specific
      synthetic ligands targeting this cell type may prove utility as a novel treatment
      for type 1 diabetes.

PMID- 25560830
TI  - Mechanisms involved in glucocorticoid induction of pituitary GH expression during
      embryonic development.
AB  - Glucocorticoid hormones are involved in functional differentiation of GH
      producing somatotrophs. Glucocorticoid treatment prematurely induces GH
      expression in mammals and birds in a process requiring protein synthesis and Rat
      sarcoma (Ras) signaling. The objective of this study was to investigate
      mechanisms through which glucocorticoids initiate GH expression during
      embryogenesis, taking advantage of the unique properties of chicken embryos as a
      developmental model. We determined that stimulation of GH expression occurred
      through transcriptional activation of GH, rather than enhancement of mRNA
      stability, and this process requires histone deacetylase activity. Through
      pharmacological inhibition, we identified the ERK1/2 pathway as a likely
      downstream Ras effector necessary for glucocorticoid stimulation of GH. However,
      we also found that chronic activation of ERK1/2 activity with a constitutively
      active mutant or stimulatory ligand reduced initiation of GH expression by
      glucocorticoid treatment. Corticosterone treatment of cultured embryonic
      pituitary cells increased ERK1/2 activity in an apparent cyclical manner, with a
      rapid increase within 5 minutes, followed by a reduction to near-basal levels at
      3 hours, and a subsequent increase again at 6 hours. Therefore, we conclude that
      ERK1/2 signaling must be strictly controlled for maximal glucocorticoid induction
      of GH to occur. These results are the first in any species to demonstrate that
      Ras- and ERK1/2-mediated transcriptional events requiring histone deacetylase
      activity are involved in glucocorticoid induction of pituitary GH during
      embryonic development. This report increases our understanding of the molecular
      mechanisms underlying glucocorticoid recruitment of somatotrophs during
      embryogenesis and should provide insight into glucocorticoid-induced
      developmental changes in other tissues and cell types.

PMID- 25560832
TI  - Comparison of sources of variability in school age children exposure to ambient
      PM2.5.
AB  - School age children are particularly susceptible to exposure to ambient fine
      particle (PM2.5). To provide insight into factors affecting variability in
      ambient PM2.5 exposure, distributions of daily PM2.5 exposures for school age
      children are estimated for four seasons in three climatic zones of the United
      States using a stochastic microenvironmental exposure model, based on ambient
      concentration, air exchange rate, penetration factor, deposition rate, census
      data, meteorological data, and time pattern data. Estimated daily individual
      exposure varies largely among seasons, regions, and individuals. The mean ratio
      of ambient exposure to ambient concentration (Ea/Ca) ranges from 0.46 to 0.61
      among selected regions and seasons, resulting from differences in air exchange
      rate. The individual Ea/Ca varies by a factor of 2 to 3 over a 95% frequency
      range among simulated children, resulting from variability in children's time
      patterns. These patterns are similar among age groups, but vary with the day of
      the week and outdoor temperature. Variability in exposure is larger between
      individuals than between groups. The high end ratio of the Ea/Ca, at the 95th
      percentile of inter-individual variability, is 30% to 50% higher than the mean
      Ea/Ca ratio. Results can be used to intepret and adjust exposure errors in
      epidemiology and to assist in development of exposure mitigation strategies. 

PMID- 25560831
TI  - Peripheral insulin resistance and impaired insulin signaling contribute to
      abnormal glucose metabolism in preterm baboons.
AB  - Premature infants develop hyperglycemia shortly after birth, increasing their
      morbidity and death. Surviving infants have increased incidence of diabetes as
      young adults. Our understanding of the biological basis for the insulin
      resistance of prematurity and developmental regulation of glucose production
      remains fragmentary. The objective of this study was to examine maturational
      differences in insulin sensitivity and the insulin-signaling pathway in skeletal
      muscle and adipose tissue of 30 neonatal baboons using the euglycemic
      hyperinsulinemic clamp. Preterm baboons (67% gestation) had reduced peripheral
      insulin sensitivity shortly after birth (M value 12.5 +/- 1.5 vs 21.8 +/- 4.4
      mg/kg . min in term baboons) and at 2 weeks of age (M value 12.8 +/- 2.6 vs 16.3
      +/- 4.2, respectively). Insulin increased Akt phosphorylation, but these
      responses were significantly lower in preterm baboons during the first week of
      life (3.2-fold vs 9.8-fold). Preterm baboons had lower glucose transporter-1
      protein content throughout the first 2 weeks of life (8%-12% of term). In preterm
      baboons, serum free fatty acids (FFAs) did not decrease in response to insulin,
      whereas FFAs decreased by greater than 80% in term baboons; the impaired
      suppression of FFAs in the preterm animals was paired with a decreased glucose
      transporter-4 protein content in adipose tissue. In conclusion, peripheral
      insulin resistance and impaired non-insulin-dependent glucose uptake play an
      important role in hyperglycemia of prematurity. Impaired insulin signaling
      (reduced Akt) contributes to the defect in insulin-stimulated glucose disposal.
      Counterregulatory hormones are not major contributors.

PMID- 25560833
TI  - The oral health care experiences of NSW Aboriginal Community Controlled Health
      Services.
AB  - OBJECTIVES: Aboriginal people continue to experience a disproportionately heavy
      burden of oral disease. A range of oral health services may be available to
      Aboriginal communities, including those provided by Aboriginal Community
      Controlled Health Services (ACCHSs). This study explored the oral health care
      experiences and activities of ACCHSs to inform policy and program decision
      making. METHODS: Mixed methods, including an online survey and semi-structured
      interviews with senior ACCHS staff, were used. Areas of inquiry included
      perceived community need for oral health care, oral health care models,
      accessibility of other oral health services and barriers to providing oral health
      care. Twenty-nine NSW ACCHSs participated in the study. RESULTS: The activities
      of NSW ACCHSs in oral health care are diverse and reflect the localised
      approaches they take to delivering primary health care. ACCHSs commonly face
      barriers in delivering oral health care, as do Aboriginal communities in
      accessing other oral health services. CONCLUSION: NSW ACCHSs are important but
      under-acknowledged providers of a range of oral health services to Aboriginal
      communities and are well placed to provide this care as part of their
      comprehensive primary health care model. IMPLICATIONS: ACCHS roles in improving
      Aboriginal oral health would be strengthened by greater acknowledgement of their
      contributions and expertise and the development of transparent, long-term funding
      policies that respond to community need.

PMID- 25560834
TI  - Minimally invasive surgery versus open surgery for the treatment of solid
      abdominal and thoracic neoplasms in children.
AB  - BACKGROUND: Minimally invasive surgery (MIS) is an accepted surgical technique
      for the treatment of a variety of benign diseases. Presently, the use of MIS in
      patients with cancer is progressing. However, the role of MIS in children with
      solid neoplasms is less clear than it is in adults. Although the use of
      diagnostic MIS to obtain biopsy specimens for pathology is accepted in paediatric
      surgical oncology, there is limited evidence to support the use of MIS for the
      resection of malignancies. This review is the second update of a previously
      published Cochrane review. OBJECTIVES: To ascertain differences in outcome
      between the minimally invasive and open surgical approaches for the treatment of
      solid intra-abdominal or intra-thoracic neoplasms in children. The primary
      outcomes of interest are OS, EFS, port-site metastases and recurrence rate; the
      secondary outcome of interest is surgical morbidity. SEARCH METHODS: We searched
      CENTRAL (The Cochrane Library 2014, Issue 1), MEDLINE/PubMed (from 1966 to
      February 2014) and EMBASE/Ovid (from 1980 to February 2014) to identify relevant
      studies. In addition, we searched reference lists of relevant articles and
      reviews and the conference proceedings of the International Society for
      Paediatric Oncology and the American Society of Clinical Oncology from 2003 to
      2013. On 1 May 2014 we scanned the ISRCTN Register (on www.controlled
      trials.com), the National Institutes of Health register (on www.controlled
      trials.com and www.clinicaltrials.gov) and the World Health Organization
      International Clinical Trials Registry Platform (on www.apps.who.int/trialsearch)
      for ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) or
      controlled clinical trials (CCTs) comparing MIS to open surgery for the treatment
      of solid intra-thoracic or intra-abdominal neoplasms in children (aged 0 to 18
      years) were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors
      performed the study selection independently. MAIN RESULTS: The literature search
      retrieved 542 references. After screening the titles and abstracts we excluded
      534 references which clearly did not meet the inclusion criteria. We assessed
      eight full text studies for eligibility and all of these studies were excluded
      from the review because they were not RCTs or CCTs. These excluded studies
      included case series, retrospective chart reviews and retrospective cohort
      studies. The scanning of reference lists and conference proceedings did not
      identify any additional studies and no (ongoing trials) were identified by the
      searches of trial registries. No studies that met the inclusion criteria of this
      review were identified AUTHORS' CONCLUSIONS: No RCTs or CCTs evaluating MIS for
      the treatment of solid intra-thoracic or intra-abdominal neoplasms in children
      could be identified. The current evidence base informing the use of MIS in
      children with solid abdominal and thoracic neoplasms is based on other study
      designs like case reports, retrospective chart reviews and cohort studies and
      should be interpreted with caution. Thus there is insufficient evidence to allow
      any definitive conclusions regarding the use of MIS in these patients. High
      quality RCTs comparing MIS to open surgery are required. To accomplish this,
      centres specialising in MIS in children should collaborate.

PMID- 25560836
TI  - Hepatitis E virus: do locally acquired infections in Australia necessitate
      laboratory testing in acute hepatitis patients with no overseas travel history?
AB  - Hepatitis E virus (HEV) is emerging as a global public health threat. Water-borne
      HEV outbreaks are common in developing countries and are associated with
      genotypes 1 and 2. In industrialised countries, sporadic cases of zoonotic
      transmission associated with genotypes 3 and 4 are increasingly being reported.
      Transfusion- and transplantation-transmitted HEV have been documented, although
      ingestion of contaminated food is thought to be the major transmission route.
      Severe disease is possible and chronic hepatitis infection occurs in solid-organ
      transplant recipients and in patients with immunosuppressive disorders. In
      Australia, HEV cases are mainly travellers returning from disease endemic
      countries. Indeed, there are few reported cases of locally acquired HEV. Pigs in
      Australia have been shown to be infected with HEV, which indicates the
      possibility of zoonotic transmission. The extent of locally acquired infection is
      not known, however it may be greater than expected and may necessitate laboratory
      testing in patients reporting no overseas travel.

PMID- 25560835
TI  - Pathway mapping and development of disease-specific biomarkers: protein-based
      network biomarkers.
AB  - It is known that a disease is rarely a consequence of an abnormality of a single
      gene, but reflects the interactions of various processes in a complex network.
      Annotated molecular networks offer new opportunities to understand diseases
      within a systems biology framework and provide an excellent substrate for network
      based identification of biomarkers. The network biomarkers and dynamic network
      biomarkers (DNBs) represent new types of biomarkers with protein-protein or gene
      gene interactions that can be monitored and evaluated at different stages and
      time-points during development of disease. Clinical bioinformatics as a new way
      to combine clinical measurements and signs with human tissue-generated
      bioinformatics is crucial to translate biomarkers into clinical application,
      validate the disease specificity, and understand the role of biomarkers in
      clinical settings. In this article, the recent advances and developments on
      network biomarkers and DNBs are comprehensively reviewed. How network biomarkers
      help a better understanding of molecular mechanism of diseases, the advantages
      and constraints of network biomarkers for clinical application, clinical
      bioinformatics as a bridge to the development of diseases-specific, stage
      specific, severity-specific and therapy predictive biomarkers, and the potentials
      of network biomarkers are also discussed. 

PMID- 25560838
TI  - Estimates on HCV disease burden worldwide - filling the gaps.
AB  - Hepatitis C is caused by infection with the hepatitis C virus (HCV) and
      represents a major global health burden. Persistent HCV infection can lead to
      progressive liver disease with the development of liver cirrhosis and
      hepatocellular carcinoma, possibly accounting for up to 0.5 million deaths every
      year. Treatment of HCV infection is undergoing a profound and radical change. As
      new treatments are extremely safe and effective, there are virtually no medical
      reasons to withhold therapy. Yet, the new therapies are expensive. As resources
      are limited, solid data to estimate the disease burden caused by HCV are urgently
      needed. Epidemiology data and disease burden analyses for 16 countries are
      presented. For almost all countries, the peak of HCV-related cirrhosis,
      hepatocellular carcinoma and liver-related death is a decade or more away.
      However, a surprising heterogeneity in country-specific HCV-associated disease
      burden exists. Also, HCV diagnosis and treatment uptake varied markedly between
      countries. A consistent finding was that a reduction of HCV liver-related
      mortality is dependent on access to therapy. Increasing efficacy of therapy alone
      with a constant numbers of treatments will not have a major impact on the HCV
      related disease burden. The data presented here should inform public health
      policy and help drive advocacy for enhanced strategic investment and action. HCV
      kills patients, and the disease burden will continue to rise in most countries
      unless action is taken soon. Chronic HCV is a curable infection and a reversible
      liver disease. Fortunately, the tools to eliminate HCV are now available. 

PMID- 25560837
TI  - Selective blockade of the hydrolysis of the endocannabinoid 2
      arachidonoylglycerol impairs learning and memory performance while producing
      antinociceptive activity in rodents.
AB  - Monoacylglycerol lipase (MAGL) represents a primary degradation enzyme of the
      endogenous cannabinoid (eCB), 2-arachidonoyglycerol (2-AG). This study reports a
      potent covalent MAGL inhibitor, SAR127303. The compound behaves as a selective
      and competitive inhibitor of mouse and human MAGL, which potently elevates
      hippocampal levels of 2-AG in mice. In vivo, SAR127303 produces antinociceptive
      effects in assays of inflammatory and visceral pain. In addition, the drug alters
      learning performance in several assays related to episodic, working and spatial
      memory. Moreover, long term potentiation (LTP) of CA1 synaptic transmission and
      acetylcholine release in the hippocampus, two hallmarks of memory function, are
      both decreased by SAR127303. Although inactive in acute seizure tests, repeated
      administration of SAR127303 delays the acquisition and decreases kindled seizures
      in mice, indicating that the drug slows down epileptogenesis, a finding deserving
      further investigation to evaluate the potential of MAGL inhibitors as
      antiepileptics. However, the observation that 2-AG hydrolysis blockade alters
      learning and memory performance, suggests that such drugs may have limited value
      as therapeutic agents. 

PMID- 25560839
TI  - Historical epidemiology of hepatitis C virus (HCV) in select countries - volume
      2.
AB  - Chronic hepatitis C virus (HCV) infection is a leading cause of liver related
      morbidity and mortality. In many countries, there is a lack of comprehensive
      epidemiological data that are crucial in implementing disease control measures as
      new treatment options become available. Published literature, unpublished data
      and expert consensus were used to determine key parameters, including prevalence,
      viremia, genotype and the number of patients diagnosed and treated. In this study
      of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91%
      in Russia. The largest viremic populations were in India (8 666 000 cases) and
      Russia (4 162 000 cases). In most countries, males had a higher rate of
      infections, likely due to higher rates of injection drug use (IDU). Estimates
      characterizing the infected population are critical to focus screening and
      treatment efforts as new therapeutic options become available.

PMID- 25560840
TI  - The present and future disease burden of hepatitis C virus (HCV) infections with
      today's treatment paradigm - volume 2.
AB  - Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection
      are increasing in many countries as the infected population ages. Models were
      developed for 15 countries to quantify and characterize the viremic population,
      as well as estimate the number of new infections and HCV related deaths from 2013
      to 2030. Expert consensus was used to determine current treatment levels and
      outcomes in each country. In most countries, viremic prevalence has already
      peaked. In every country studied, prevalence begins to decline before 2030, when
      current treatment levels were held constant. In contrast, cases of advanced liver
      disease and liver related deaths will continue to increase through 2030 in most
      countries. The current treatment paradigm is inadequate if large reductions in
      HCV related morbidity and mortality are to be achieved. 

PMID- 25560842
TI  - LFCseq: a nonparametric approach for differential expression analysis of RNA-seq
      data.
AB  - BACKGROUND: With the advances in high-throughput DNA sequencing technologies, RNA
      seq has rapidly emerged as a powerful tool for the quantitative analysis of gene
      expression and transcript variant discovery. In comparative experiments,
      differential expression analysis is commonly performed on RNA-seq data to
      identify genes/features that are differentially expressed between biological
      conditions. Most existing statistical methods for differential expression
      analysis are parametric and assume either Poisson distribution or negative
      binomial distribution on gene read counts. However, violation of distributional
      assumptions or a poor estimation of parameters often leads to unreliable results.
      RESULTS: In this paper, we introduce a new nonparametric approach called LFCseq
      that uses log fold changes as a differential expression test statistic. To test
      each gene for differential expression, LFCseq estimates a null probability
      distribution of count changes from a selected set of genes with similar
      expression strength. In contrast, the nonparametric NOISeq approach relies on a
      null distribution estimated from all genes within an experimental condition
      regardless of their expression levels. CONCLUSION: Through extensive simulation
      study and RNA-seq real data analysis, we demonstrate that the proposed approach
      could well rank the differentially expressed genes ahead of non-differentially
      expressed genes, thereby achieving a much improved overall performance for
      differential expression analysis.

PMID- 25560841
TI  - Strategies to manage hepatitis C virus (HCV) infection disease burden - volume 2.
AB  - The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15
      countries, and the relative impact of two scenarios was considered: (i) increased
      treatment efficacy while holding the treated population constant and (ii)
      increased treatment efficacy and increased annual treated population. Increasing
      levels of diagnosis and treatment, in combination with improved treatment
      efficacy, were critical for achieving substantial reductions in disease burden.
      In most countries, the annual treated population had to increase several fold to
      achieve the largest reductions in HCV-related morbidity and mortality. This
      suggests that increased capacity for screening and treatment will be critical in
      many countries. Birth cohort screening is a helpful tool for maximizing
      resources. In most of the studied countries, the majority of patients were born
      between 1945 and 1985. 

PMID- 25560843
TI  - Complementary and alternative medicine: Interaction and communication between
      midwives and women.
AB  - BACKGROUND: Many pregnant women use complementary and alternative medicine.
      Although midwives are often supportive, how they communicate with women about the
      safe use of these therapies has received limited research attention. AIM: The aim
      of this study was to explore how midwives interact with women regarding use of
      complementary and alternative medicine during pregnancy. METHODS: We utilised
      grounded theory methodology to collect and analyse data. Twenty-five midwives who
      worked in metropolitan hospitals situated in Melbourne, Australia, participated
      in the study. Data were collected from semi structured interviews and non
      participant observations, over an 18-month period. FINDINGS: How midwives
      communicate about complementary and alternative medicine is closely associated
      with the meaning they construct around the woman's role in decisionmaking. Most
      aim to work in a manner consistent with the midwifery partnership model and share
      the responsibility for decisions regarding complementary and alternative
      medicine. However, although various therapies were commonly discussed, usually
      the pregnant woman initiated the dialogue. A number of contextual conditions such
      as the biomedical discourse, lack of knowledge, language barriers and workplace
      constraints, limited communication in some situations. CONCLUSION: Midwives often
      interact with women interested in using CAM. Most value the woman's autonomy and
      aim to work in partnership. However, various contextual conditions restrain overt
      CAM communication in clinical practice.

PMID- 25560844
TI  - NAFLD in 2014: Genetics, diagnostics and therapeutic advances in NAFLD.

PMID- 25560845
TI  - Liver: Sussing out statins in cirrhosis--KLF2 is the key.

PMID- 25560846
TI  - Pancreatic disease in 2014: Pancreatic fibrosis and standard diagnostics.

PMID- 25560848
TI  - Stability of hydrophilic vitamins mixtures in the presence of electrolytes and
      trace elements for parenteral nutrition: a nuclear magnetic resonance
      spectroscopy investigation.
AB  - In total parenteral nutrition (TPN), especially in the case of preterm infants,
      simultaneous administration of vitamins and trace elements is still a problematic
      issue: guidelines put in evidence the lack of specific documentation. In this
      work NMR spectroscopy was applied to the study of vitamins (pyridoxine
      hydrochloride, thiamine nitrate, riboflavin-5'-phosphate and nicotinamide)
      stability in presence of salts and trace elements. Vitamins in D2O were first
      analyzed by (1)H NMR spectroscopy in absence of salts and trace elements; changes
      in chemical shifts or in diffusion coefficients, measured by NMR DOSY technique,
      were analyzed. The effects of salts and trace elements on single vitamins and on
      their admixtures were then investigated by performing quantitative analyses
      during 48h. Selected vitamins are subject to intermolecular interactions. No
      degradative effects were observed in presence of salts and trace elements. Only
      riboflavin-5'-phosphate is subject to precipitation in presence of divalent
      cations; however, at low concentration and in presence of other vitamins this
      effect was not observed. Solutions analyzed, in the condition of this study, are
      stable for at least 48h and vitamins and trace elements can be administered
      together in TPN. 

PMID- 25560849
TI  - Spread the Word About CHEST in 2015: Rising Impact Factor, Continuous
      Innovations, and Changes to the Editorial Team.

PMID- 25560847
TI  - Stress-related mucosal disease in the critically ill patient.
AB  - Bleeding from stress-related mucosal disease in critically ill patients remains
      an important clinical management issue. Although only a small proportion (1-6%)
      of patients admitted to an intensive care unit (ICU) will bleed, a substantial
      proportion exhibit clinical risk factors (mechanical ventilation for >48 h and a
      coagulopathy) that predict an increased risk of bleeding. Furthermore, upper
      gastrointestinal mucosal lesions can be found in 75-100% of patients in ICUs.
      Although uncommon, stress-ulcer bleeding is a severe complication with an
      estimated mortality of 40-50%, mostly from decompensating an underlying condition
      or multiorgan failure. Although the vast majority of patients in ICUs receive
      stress-ulcer prophylaxis, largely with PPIs, some controversy surrounds their
      efficacy and safety. Indeed, no single trial has shown that stress-ulcer
      prophylaxis reduces mortality. Some reports suggest that the use of PPIs
      increases the risk of nosocomial infections. However, several meta-analyses and
      cost-effectiveness studies suggest PPIs to be more clinically effective and cost
      effective than histamine-2 receptor antagonists, without considerable increases
      in nosocomial pneumonia. To help clinicians use the most appropriate strategy for
      treatment of patients in the ICU, this Review presents the latest information on
      all aspects of stress-related mucosal disease. 

PMID- 25560850
TI  - Counting costs in COPD: what do the numbers mean?

PMID- 25560851
TI  - Managing ventilator complications in a "VACuum" of data.

PMID- 25560852
TI  - ARDS: lessons learned from the heart.

PMID- 25560853
TI  - The epidemiologic threat of atrial fibrillation: need for secondary, primary, and
      primordial prevention.

PMID- 25560854
TI  - Point: Are the CHEST guidelines global in coverage? Yes.

PMID- 25560855
TI  - Counterpoint: Are the CHEST guidelines global in coverage? No.

PMID- 25560856
TI  - Rebuttal from Drs Nathanson and Ouellette.

PMID- 25560857
TI  - Rebuttal from Dr Mehta et al.

PMID- 25560858
TI  - Giants in chest medicine: Edward C. Rosenow III, MD, Master FCCP.

PMID- 25560859
TI  - Future of thoracic PET scanning.
AB  - The advances in PET scanning for thoracic diseases that are deemed most likely to
      have clinical impact in the near-term future are highlighted in this article. We
      predict that the current practice of medicine will continue to embrace the power
      of molecular imaging and specifically PET scanning. 18F-fluorodeoxyglucose-PET
      scanning will continue to evolve and will expand into imaging of inflammatory
      disorders. New clinically available PET scan radiotracers, such as PET scan
      versions of octreotide and amyloid imaging agents, will expand PET imaging into
      different disease processes. Major improvements in thoracic PET/CT imaging
      technology will become available, including fully digital silicone
      photomultipliers and Bayesian penalized likelihood image reconstruction. These
      will result in significant improvements in image quality, improving the
      evaluation of smaller lung nodules and metastases and allowing better prediction
      of prognosis. The birth of clinical PET/MRI scan will add new imaging
      opportunities, such as better PET imaging of pleural diseases currently obscured
      by complex patient motion. 

PMID- 25560860
TI  - Breathomics in lung disease.
AB  - Volatile organic compounds (VOCs) are produced by virtually all metabolic
      processes of the body. As such, they have potential to serve as noninvasive
      metabolic biomarkers. Since exhaled VOCs are either derived from the respiratory
      tract itself or have passed the lungs from the circulation, they are candidate
      biomarkers in the diagnosis and monitoring of pulmonary diseases in particular.
      Good examples of the possibilities of exhaled volatiles in pulmonary medicine are
      provided by the potential use of VOCs to discriminate between patients with lung
      cancer and healthy control subjects and to noninvasively diagnose infectious
      diseases and the association between VOCs and markers of disease activity that
      has been established in obstructive lung diseases. Several steps are, however,
      required prior to implementation of breath-based diagnostics in daily clinical
      practice. First, VOCs should be studied in the intention-to-diagnose population,
      because biomarkers are likely to be affected by multiple (comorbid) conditions.
      Second, breath collection and analysis procedures need to be standardized to
      allow pooling of data. Finally, apart from probabilistic analysis for diagnostic
      purposes, detailed examination of the nature of volatile biomarkers not only will
      improve our understanding of the pathophysiologic origins of these markers and
      the nature of potential confounders but also can enable the development of
      sensors that exhibit maximum sensitivity and specificity toward specific
      applications. By adhering to such an approach, exhaled biomarkers can be
      validated in the diagnosis, monitoring, and treatment of patients in pulmonary
      medicine and contribute to the development of personalized medicine. 

PMID- 25560861
TI  - Recent advances in dyspnea.
AB  - Dyspnea is the most prevalent symptom among patients with cardiac and respiratory
      diseases. It is an independent predictor of mortality in patients with heart
      disease, COPD, and the elderly. Studies using naloxone to block opioid-receptor
      signaling demonstrate that endogenous opioids modulate dyspnea in patients with
      COPD. Neuroimaging studies support a cortical-limbic network for dyspnea
      perception. A 2012 American Thoracic Society statement recommended that dyspnea
      be considered across three different constructs: sensory (intensity), affective
      (distress), and impact on daily activities. The 2013 GOLD (Global Initiative for
      Chronic Obstructive Lung Disease) executive summary recommended a treatment
      paradigm for patients with COPD based on the modified Medical Research Council
      dyspnea score. The intensity and quality of dyspnea during exercise in patients
      with COPD is influenced by the time to onset of critical mechanical volume
      constraints that are ultimately dictated by the magnitude of resting inspiratory
      capacity. Long-acting bronchodilators, either singly or in combination, provide
      sustained bronchodilation and lung deflation that contribute to relief of dyspnea
      in those with COPD. Opioid medications reduce breathing discomfort by decreasing
      respiratory drive (and associated corollary discharge), altering central
      perception, and/or decreasing anxiety. For individuals suffering from refractory
      dyspnea, a low dose of an opioid is recommended initially, and then titrated to
      achieve the lowest effective dose based on patient ratings. Acupuncture,
      bronchoscopic volume reduction, and noninvasive open ventilation are experimental
      approaches shown to ameliorate dyspnea in patients with COPD, but require
      confirmatory evidence before clinical use. 

PMID- 25560862
TI  - "Pills" and the air passages: a continuum.
AB  - Recently, we reported a number of key, common medications that affect the air
      passages in a variety of fashions. The purpose of this article is to provide a
      comprehensive review of the literature on the subject, including supportive
      articles published in languages other than English. The presented information was
      gathered by a review of the English literature, by cross referencing, and by
      communication with other interventional pulmonologists. We identified several
      additional medications causing either direct or systemic effects on the air
      passages. In this review, we update the clinical presentation, mechanism of
      injury, diagnosis, and management of the airway complications related to these
      medications. 

PMID- 25560863
TI  - Rationale for specific allergen testing of patients with asthma in the clinical
      pulmonary office setting.
AB  - Asthma is a chronic inflammatory disease that affects an estimated 25 million
      people in the United States. In 70% to 90% of cases, asthma is associated with
      IgE-mediated mechanisms, which have proved central to allergen-induced
      inflammation in preclinical and clinical models. The importance of IgE levels in
      patients with moderate to severe asthma has been confirmed in randomized
      controlled studies with a targeted IgE blocker. Advances in laboratory methods to
      detect and quantify allergen-specific IgE antibodies have allowed for a quick-and
      easy diagnosis of allergic IgE-mediated sensitivities in the office.
      Pulmonologists tend to order in vitro tests to measure allergen-specific IgE
      rather than to perform allergen skin testing, which is seen as the purview of
      allergists. This article reviews the importance of allergen testing in patients
      with asthma-whether by skin testing or by in vitro methods-and highlights the
      advantages, limitations, and interpretation of results derived from each method.
      Additionally, this article includes suggested documentation and administrative
      details for physician reporting in the office setting.

PMID- 25560864
TI  - Acute cor pulmonale in ARDS: rationale for protecting the right ventricle.
AB  - The ventilatory strategy for ARDS has been regularly amended over the last 40
      years as knowledge of the pathophysiology of ARDS has increased. Initially
      focused mainly on the lung with the objectives of "opening the lung" and
      optimizing arterial oxygen saturation, this strategy now also takes into account
      pulmonary vascular injury and its effects on the right ventricle and on
      hemodynamics. Hemodynamic devices now available at the bedside, such as
      echocardiography, allow intensivists to evaluate respiratory settings according
      to right ventricular tolerance. Here, we review the pathophysiology of pulmonary
      vascular dysfunction in ARDS, consider the beneficial and deleterious effects of
      mechanical ventilation, describe the incidence and meaning of acute cor pulmonale
      based on recent studies in large series of patients, and propose a new, although
      not strictly validated, approach based on the protection of both the lung and
      right ventricle. One of our conclusions is that evaluating the right ventricle
      may help intensivists to assess the balance between recruitment and
      overdistension induced by the ventilatory strategy. Prone positioning with its
      beneficial effects on the lung and also on hemodynamics (the right ventricle) is
      a good illustration of this. Readers should be aware that most of the information
      given in this article reflects the point of view of the authors. Although based
      on clinical observations, clinical studies, and well-known pathophysiology, there
      is no evidence-based medicine to support this clinical commentary. Other
      approaches may be favored, in which case our article should be read as another
      attempt to help intensivists to improve management of ARDS. 

PMID- 25560866
TI  - A 75-year-old woman with fever and a right upper lobe pulmonary mass.

PMID- 25560867
TI  - A 65-year-old man with persistent cough and large nodular opacity.
AB  - A 65-year-old Asian man with a history of chronic hepatitis B infection presented
      to our pulmonary clinic for second opinion of his chronic, persistent,
      nonproductive cough. He was evaluated 10 months earlier with chest CT scan, which
      revealed a large lingular nodular opacity that was diagnosed as nodular
      cryptogenic organizing pneumonia by CT scan-guided percutaneous lung biopsy.
      Systemic corticosteroids were initiated and continued over the next 10 months.
      The dry cough persisted, and he developed intermittent left-sided pleuritic chest
      pain. He denied fevers, night sweats, hemoptysis, weight loss, or dyspnea. He was
      a lifelong nonsmoker and moved to the United States from China during childhood. 

PMID- 25560865
TI  - Intermittent hypoxemia and OSA: implications for comorbidities.
AB  - OSA is a common chronic disorder that is associated with significant morbidity
      and mortality including cardiovascular, metabolic, and neurocognitive disease and
      increased cancer-related deaths. OSA is characterized by recurrent episodes of
      apneas and hypopneas associated with repetitive episodes of intermittent
      hypoxemia, intrathoracic pressure changes, and arousals. Intermittent hypoxemia
      (IH) is now being recognized as a potential major factor contributing to the
      pathogenesis of OSA-related comorbidities. OSA-related high-frequency IH is
      characterized by cycles of hypoxemia with reoxygenation that is distinctly
      different than sustained low-frequency hypoxia and contributes to ischemia
      reperfusion injury. Data from both animal and human studies support mechanistic
      links between IH and its adverse impact at the tissue level. IH promotes
      oxidative stress by increased production of reactive oxygen species and
      angiogenesis, increased sympathetic activation with BP elevation, and systemic
      and vascular inflammation with endothelial dysfunction that contributes to
      diverse multiorgan chronic morbidity and mortality affecting cardiovascular
      disease, metabolic dysfunction, cognitive decline, and progression of cancer.
      Data from observational studies in large population groups also support the role
      for hypoxia in the pathogenesis of OSA comorbidity. Treatment with CPAP to
      reverse OSA-related symptoms and comorbidities has been shown to provide variable
      benefit in some but not all patient groups. Early treatment with CPAP makes
      intuitive sense to promote maximal functional recovery and minimize residual
      injury. More studies are needed to determine the interacting effects of IH and
      obesity, differential effects of both short-term and long-term hypoxemia, and the
      effect of CPAP treatment. 

PMID- 25560868
TI  - A 44-year-old woman with metabolic acidosis, high anion gap, and delayed
      neurologic deterioration.
AB  - A 44-year-old woman was brought to the ED from John F. Kennedy International
      Airport. The patient was returning with her son from a 3-month visit to
      Bangladesh. Her journey started with a 4-h flight from Dhaka, Bangladesh to
      Dubai, United Arab Emirates. She consumed 240 mL of whiskey during the flight.
      This was followed by a 14-h flight from Dubai to New York. According to the
      patient's son, she did not consume any alcohol during the second flight. The
      patient was in her usual state of health with normal mentation throughout her
      journey. Upon landing, she started complaining of shortness of breath. After
      disembarking, she was witnessed to have seizure-like activity with involuntary
      passage of urine, following which she collapsed. The patient was intubated by
      emergency medical services in the field.

PMID- 25560869
TI  - The unfortunate research inertia on studying VTE in nursing homes.

PMID- 25560870
TI  - Point-of-care ultrasonography: ready to take off?

PMID- 25560871
TI  - Response.

PMID- 25560872
TI  - Development and implementation of a cohort review for latent TB infection.

PMID- 25560873
TI  - Avoiding vessel laceration in thoracentesis: a role of vascular ultrasound with
      color Doppler.
AB  - Thoracentesis is considered a relatively safe and well-established procedure
      commonly done at the bedside with minimal risk of complication. Thoracentesis
      related hemothorax is uncommon; however, it may be life-threatening. We describe
      a case of a 19-year-old woman with persistent fever and pleural effusion, in
      which thoracentesis resulted in tension hemothorax due to intercostal artery
      laceration. It is important for proceduralists to understand not only the
      tortuosity of the intercostal artery covering 25% to 50% of the intercostal
      space, but also the presence of traversing collateral arteries. Herein, we
      discuss the potential benefit of vascular ultrasonography with color Doppler
      during thoracentesis, with the goal of avoiding vessel injury and hemorrhage. 

PMID- 25560874
TI  - A 47-year-old returning traveler with shock.
AB  - A 47-year-old man with no significant past medical history, originally from
      Indonesia, was brought to the ED of an urban US medical center after being found
      collapsed on the sidewalk in respiratory distress and with an altered sensorium.
      Upon arrival to the ED, he was tachypneic, with increased work of breathing and
      an oxygen saturation of 88% on 100% nonrebreather mask, so he was immediately
      intubated. Following intubation, he became profoundly hypotensive, requiring
      aggressive crystalloid resuscitation and vasopressor support. Broad-spectrum
      antimicrobials were administered, including ceftriaxone, vancomycin,
      levofloxacin, and oseltamivir. Further history elicited subsequently from family
      members revealed that the patient had returned from a 2-week vacation in
      Indonesia 6 days prior to presentation. According to relatives, he appeared to be
      in his usual state of health upon his return and was not seen by anyone
      thereafter, but in the interim he reportedly had an episode of epistaxis, and
      text messages received from him became progressively more bizarre.

PMID- 25560875
TI  - C-reactive protein on postoperative day 3 as a predictor of infectious
      complications following gastric cancer resection.
AB  - BACKGROUND: Postoperative infectious complications (PICs) after gastric cancer
      resection remain a clinically relevant problem. Early detection of PICs, before
      critical illness develops, may be of considerable clinical benefit. The aims of
      this study were to investigate the predictive factors for PICs and to define the
      clinical parameters for detecting them early in patients with gastric cancer
      resection. METHODS: Clinical data for 417 consecutive patients undergoing
      elective gastrectomy for primary gastric cancer between 2009 and 2012 were
      retrospectively analyzed. Diagnostic accuracy was determined by the area under
      the receiver operating characteristic curve (AUC). Univariate and multivariate
      logistic regression analyses identified clinical factors predicting PICs of grade
      III or more according to the Clavien-Dindo classification. RESULTS: Forty-four
      patients developed PICs of grade >= III [10.6%, 95% confidence interval (CI) 7.6
      13.5%]. As a systemic inflammatory marker, C-reactive protein (CRP) on
      postoperative day (POD) 3 had superior diagnostic accuracy for PICs (AUC 0.802,
      95% CI 0.735-0.870) with a calculated cutoff value of 17.7 mg/dl, yielding a
      sensitivity of 0.66 (95% CI 0.524-0.774) and a specificity of 0.84 (95% CI 0.821
      0.850). Multivariate analysis identified CRP on POD 3 of 17.7 mg/dl or greater
      [odds ratio (OR) 8.094, 95% CI 3.568-19.342) as well as clinical stage >= II (OR
      4.445, 95% CI 1.478-15.881) and operation time >= 250 min (OR 3.638, 95% CI 1.449
      10.137) as significant predictive factors for PICs after gastrectomy.
      CONCLUSIONS: Elevated CRP levels on POD 3 will help physicians predict the
      postoperative course and facilitate decision-making regarding prompt,
      comprehensive clinical searches and therapeutic approaches for PICs.

PMID- 25560876
TI  - Human papillomavirus and the incidence of nonmelanoma and melanoma skin cancer
      using cervical conization as a surrogate marker: a nationwide population-based
      Danish cohort study.
AB  - PURPOSE: Human papillomavirus' (HPV's) role in skin cancer is controversial. To
      examine whether an individual is prone to develop a chronic oncogenic infection,
      we conducted a nationwide population-based cohort study of the risk of skin
      cancer after another HPV-related neoplasia-that is, cervical high-grade dysplasia
      or carcinoma-using cervical conization as a surrogate marker. METHODS: Using
      Danish registries, we identified all women who underwent conization from 1978 to
      2011 (n = 87,164) and followed them until first-time skin cancer diagnosis,
      death, emigration, or 31 December 2011, whichever came first. We calculated
      standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for basal
      cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM)
      according to national incidence rates. RESULTS: The 1-year absolute risks were
      0.0012%, 0.045%, and 0.029% for SCC, BCC, and MM, respectively. Conization was
      clearly associated with increased incidence of SCC (SIR = 1.37; 95% CI: 1.13
      1.65), but not MM (SIR = 1.00; 95% CI: 0.91-1.11). BCC risk was slightly
      increased (SIR = 1.08; 95% CI: 1.02-1.13). CONCLUSIONS: The association between
      conization and cutaneous SCC provides evidence for conization as a marker of
      underlying general susceptibility to oncogenic HPV.

PMID- 25560877
TI  - Network of GRAS transcription factors involved in the control of arbuscule
      development in Lotus japonicus.
AB  - Arbuscular mycorrhizal (AM) fungi, in symbiosis with plants, facilitate
      acquisition of nutrients from the soil to their host. After penetration,
      intracellular hyphae form fine-branched structures in cortical cells termed
      arbuscules, representing the major site where bidirectional nutrient exchange
      takes place between the host plant and fungus. Transcriptional mechanisms
      underlying this cellular reprogramming are still poorly understood. GRAS proteins
      are an important family of transcriptional regulators in plants, named after the
      first three members: GIBBERELLIC ACID-INSENSITIVE, REPRESSOR of GAI, and
      SCARECROW. Here, we show that among 45 transcription factors up-regulated in
      mycorrhizal roots of the legume Lotus japonicus, expression of a unique GRAS
      protein particularly increases in arbuscule-containing cells under low phosphate
      conditions and displays a phylogenetic pattern characteristic of symbiotic genes.
      Allelic rad1 mutants display a strongly reduced number of arbuscules, which
      undergo accelerated degeneration. In further studies, two RAD1-interacting
      proteins were identified. One of them is the closest homolog of Medicago
      truncatula, REDUCED ARBUSCULAR MYCORRHIZATION1 (RAM1), which was reported to
      regulate a glycerol-3-phosphate acyl transferase that promotes cutin biosynthesis
      to enhance hyphopodia formation. As in M. truncatula, the L. japonicus ram1
      mutant lines show compromised AM colonization and stunted arbuscules. Our
      findings provide, to our knowledge, new insight into the transcriptional program
      underlying the host's response to AM colonization and propose a function of GRAS
      transcription factors including RAD1 and RAM1 during arbuscule development. 

PMID- 25560878
TI  - TYPE-ONE PROTEIN PHOSPHATASE4 regulates pavement cell interdigitation by
      modulating PIN-FORMED1 polarity and trafficking in Arabidopsis.
AB  - In plants, cell morphogenesis is dependent on intercellular auxin accumulation.
      The polar subcellular localization of the PIN-FORMED (PIN) protein is crucial for
      this process. Previous studies have shown that the protein kinase PINOID (PID)
      and protein phosphatase6-type phosphatase holoenzyme regulate the phosphorylation
      status of PIN1 in root tips and shoot apices. Here, we show that a type-one
      protein phosphatase, TOPP4, is essential for the formation of interdigitated
      pavement cell (PC) pattern in Arabidopsis (Arabidopsis thaliana) leaf. The
      dominant-negative mutant topp4-1 showed severely inhibited interdigitated PC
      growth. Expression of topp4-1 gene in wild-type plants recapitulated the PC
      defects in the mutant. Genetic analyses suggested that TOPP4 and PIN1 likely
      function in the same pathway to regulate PC morphogenesis. Furthermore,
      colocalization, in vitro and in vivo protein interaction studies, and
      dephosphorylation assays revealed that TOPP4 mediated PIN1 polar localization and
      endocytic trafficking in PCs by acting antagonistically with PID to modulate the
      phosphorylation status of PIN1. In addition, TOPP4 affects the cytoskeleton
      pattern through the Rho of Plant GTPase-dependent auxin-signaling pathway.
      Therefore, we conclude that TOPP4-regulated PIN1 polar targeting through direct
      dephosphorylation is crucial for PC morphogenesis in the Arabidopsis leaf. 

PMID- 25560879
TI  - A KNOTTED1-LIKE HOMEOBOX protein regulates abscission in tomato by modulating the
      auxin pathway.
AB  - A gene encoding a KNOTTED1-LIKE HOMEOBOX PROTEIN1 (KD1) is highly expressed in
      both leaf and flower abscission zones. Reducing the abundance of transcripts of
      this gene in tomato (Solanum lycopersicum) by both virus-induced gene silencing
      and stable transformation with a silencing construct driven by an abscission
      specific promoter resulted in a striking retardation of pedicel and petiole
      abscission. In contrast, Petroselinum, a semidominant KD1 mutant, showed
      accelerated pedicel and petiole abscission. Complementary DNA microarray and
      quantitative reverse transcription-polymerase chain reaction analysis indicated
      that regulation of abscission by KD1 was associated with changed abundance of
      genes related to auxin transporters and signaling components. Measurement of
      auxin content and activity of a DR5::beta-glucuronidase auxin reporter assay
      showed that changes in KD1 expression modulated the auxin concentration and
      response gradient in the abscission zone.

PMID- 25560881
TI  - Systematic mixed-methods review of interventions, outcomes and experiences for
      imprisoned pregnant women.
AB  - AIMS: To review published studies reporting maternity experiences and outcomes
      for pregnant incarcerated women and their babies. BACKGROUND: Numbers of women in
      prison have increased in many countries. Imprisoned women who are pregnant are
      particularly vulnerable and marginalised. Little is known about their maternity
      care experiences, or outcomes. DESIGN: Systematic mixed-methods review using a
      segregated approach. DATA SOURCES: The Cochrane Library, CINAHL, EMBASE, MEDLINE
      Psych INFO and PubMed were searched using the terms 'mother' and 'prison',
      (January 1995-July 2012). From July 2012-May 2014 possible new studies were
      identified through scrutiny of 50 relevant journal contents pages via Zetoc.
      RESULTS: Seven studies met the review criteria and quality standards, all from
      the USA or UK. Four of the studies were quantitative; two were qualitative; and
      one used mixed-methods. None reported the outcomes of an intervention.
      Examination of the quantitative data identified a complex picture of potential
      harms and benefits for babies born in prison. Qualitative data revealed the
      unique needs of childbearing women in prison, as they continuously negotiate
      being an inmate, becoming a mother, complex social histories and the threat of
      losing their baby, all coalescing with opportunities for transformation offered
      by pregnancy. CONCLUSIONS: There is very limited published data on the
      experiences and outcomes of childbearing women in prison. There appear to be no
      good quality intervention studies examining the effectiveness of interventions to
      improve well-being in the short or longer term for these women and their babies.

PMID- 25560882
TI  - Diastereoselective 1,3-dipolar cycloaddition of nitrones to donor-acceptor
      cyclopropanes catalyzed by a calcium(II) complex.
AB  - Calcium triflate has been identified as an efficient catalyst for the
      cycloaddition of nitrones to donor-acceptor cyclopropanes. The reaction proceeds
      with good to excellent yields of the corresponding tetrahydro-1,2-oxazines with
      high levels of diastereoselectivity. The generality of the reaction allowed for
      the synthesis of tetrahydro-1,2-oxazines bearing alkyl, aryl, and heteroaromatic
      substitution. 

PMID- 25560880
TI  - Insights into the origin and evolution of the plant hormone signaling machinery.
AB  - Plant hormones modulate plant growth, development, and defense. However, many
      aspects of the origin and evolution of plant hormone signaling pathways remain
      obscure. Here, we use a comparative genomic and phylogenetic approach to
      investigate the origin and evolution of nine major plant hormone (abscisic acid,
      auxin, brassinosteroid, cytokinin, ethylene, gibberellin, jasmonate, salicylic
      acid, and strigolactone) signaling pathways. Our multispecies genome-wide
      analysis reveals that: (1) auxin, cytokinin, and strigolactone signaling pathways
      originated in charophyte lineages; (2) abscisic acid, jasmonate, and salicylic
      acid signaling pathways arose in the last common ancestor of land plants; (3)
      gibberellin signaling evolved after the divergence of bryophytes from land
      plants; (4) the canonical brassinosteroid signaling originated before the
      emergence of angiosperms but likely after the split of gymnosperms and
      angiosperms; and (5) the origin of the canonical ethylene signaling pathway
      postdates shortly the emergence of angiosperms. Our findings might have important
      implications in understanding the molecular mechanisms underlying the emergence
      of land plants. 

PMID- 25560883
TI  - Straightforward synthesis of novel enantiopure alpha-trifluoromethylated
      azetidine 2-carboxylic acid and homoserines.
AB  - The straightforward syntheses of enantiopure (2R)-2-trifluoromethyl-2
      carboxyazetidine and (R)- and (S)-trifluoromethylhomoserines are reported. The
      key step is a Strecker-type reaction on a common chiral CF3-containing bicyclic
      oxazolidine intermediate obtained by a condensation reaction of (R)
      phenylglycinol and ethyl-4,4,4-trifluoroacetoacetate (ETFAA). 

PMID- 25560884
TI  - Canadian public health under siege.

PMID- 25560885
TI  - Neighbourhood immigrant concentration and hospitalization: a multilevel analysis
      of cardiovascular-related admissions in Ontario using linked data.
AB  - OBJECTIVE: To assess the influence of neighbourhood immigrant concentration on
      cardiovascular-disease-related hospitalizations in Canada (CVDH), while adjusting
      for individual-level immigrant status and socio-economic indicators at individual
      and neighbourhood levels. METHODS: Data were from the 2006 Canadian Census linked
      to the hospital Discharge Abstract Data (DAD) for the province of Ontario. Adults
      (n=1,459,950) aged >=18 years at baseline and grouped by place of birth (Canada,
      China, South Asia, Europe, and other) were followed between Census Day May 16,
      2006 and March 31, 2008. Information on CVDH was obtained from the DAD, while
      that on immigration and socio-economic indicators was obtained from the Census.
      The analysis used multilevel logistic regression. RESULTS: Unadjusted results
      showed that CVDH was significantly lower among people living in neighbourhoods
      with medium and high immigrant concentration. Neighbourhood immigrant
      concentration tended to have no independent effect on CVDH after adjustment for
      individual-level immigrant status. Immigrants were less likely to experience CVDH
      irrespective of their country of birth. However, cross-level interaction showed
      that neighbourhood immigrant concentration provided additional protection to
      individual-level immigrant status against CVDH for most female immigrant groups,
      but only for South Asian males. CONCLUSION: This study resulted from the first
      ever linkage of census data to hospitalization data in Canada. It is also the
      first Canadian study to report on neighbourhood variation and the effect of
      immigrant concentration on CVDH. The study shows that understanding immigrant
      health requires both individual and neighbourhood approaches, and a consideration
      of country of origin.

PMID- 25560886
TI  - Correlates of physical activity among First Nations children residing in First
      Nations communities in Canada.
AB  - OBJECTIVES: Physical activity has numerous mental, emotional, spiritual and
      physical benefits. The factors influencing physical activity among First Nations
      children have not been well studied. The objective was to examine the
      associations between several intrapersonal, family and community factors and
      physical activity among First Nations school-aged children residing in First
      Nations communities. METHODS: Participants consisted of 3,184 children (6-11
      years old) from the 2008/10 First Nations Regional Health Survey, a
      representative sample of First Nations persons who reside in on-reserve and
      northern First Nations communities. The survey addresses a holistic range of
      health issues. Primary caregivers completed interviews to assess each child's
      moderate-to-vigorous physical activity (MVPA), participation in traditional
      physical activities, six intrapersonal factors, four family factors and two
      community factors. RESULTS: Based on primary caregiver reports, 72% of children
      accumulated a daily average of >=60 minutes of MVPA and 54% participated in at
      least one traditional First Nations physical activity in the past year. Older
      age, having more people in the household, and having more relatives help the
      child understand their culture were independently associated with accumulating
      >=60 minutes of MVPA. School attendance, use of First Nations language, having
      parents with a high school education, smaller community size, and having more
      community members help the child understand their culture were independently
      associated with participation in traditional First Nations physical activities.
      CONCLUSION: Among First Nations children, there are several correlates of
      physical activity from diverse ecological levels.

PMID- 25560887
TI  - Obesity, lifestyle and socio-economic determinants of vitamin D intake: a
      population-based study of Canadian children.
AB  - OBJECTIVE: Vitamin D intake in childhood is primarily for the prevention of
      rickets. Inconsistent evidence has associated adequate blood concentrations with
      a decreased risk of certain health conditions. Further, obese individuals may
      have lower vitamin D status. The estimated average requirement (EAR) for children
      recently doubled to 400 IU/day. Our aim was to examine dietary intake of vitamin
      D in different body mass index (BMI) categories, in addition to assessing
      determinants. METHODS: Data from two provincial surveys of grade 5 children,
      including a food frequency questionnaire and measured BMI, were used. Rao-Scott
      chi-square statistic tested the bivariate association between provinces and
      adequate dietary vitamin D intake. Key correlates were examined using multi-level
      logistic regression. RESULTS: Those below the EAR differed between Alberta (78%)
      and Nova Scotia (81%). Those drinking <2 glasses of milk/day had 0.02 times the
      odds of meeting the EAR (95% CI: 0.01-0.02) compared to those drinking more. No
      significant difference was observed for BMI, though those consuming <1 glass of
      milk/day were more likely to be obese than those consuming >=2 glasses/day.
      Income and physical activity were negatively correlated with meeting the EAR.
      CONCLUSION: Many children did not meet the EAR for vitamin D from dietary sources
      and milk consumption was an important determinant. Given trends towards a more
      sedentary lifestyle and limited sun exposure, we recommend prioritizing public
      health efforts to support dietary vitamin D intake alongside interventions to
      increase physical activity and reduce sedentary behaviour. Further investigation
      is required to determine the need for targeted strategies for obese children.

PMID- 25560888
TI  - [Participation of parents in a nutritional education program in schools and
      development of eating behaviours of children].
AB  - GOALS: To describe the various dimensions of parental involvement in the
      interventions initiated in schools and to identify the relationship between each
      of these dimensions and the development of children's food choices following
      their exposure to a nutrition-education project implemented in eight primary
      schools in underprivileged neighbourhoods in Montreal - the Junior Cooks -
      Parents Network project (Petits cuistots - Parents en reseaux (PC-PR)). METHOD:
      This descriptive research was conducted thanks to a secondary analysis of data
      from a sample of 502 parents of children attending schools that participated in
      the PC-PR project. Parental participation is described in four aspects, making
      reference to the idea of a mesosystem, suggested by Bronfenbrenner (1979).
      Children's eating-related behaviour, as reported by the parents, included:
      talking about workshops, asking to buy certain foods, reading labels on product
      wrapping and helping to prepare the meal. Bivariate and multivariate descriptive
      analyses were performed. RESULTS: The data gathered from the parents show a
      positive association between in-home parental involvement and overall food
      behaviour in the students. However, there is no association between parental
      involvement at school and any of the behaviours. CONCLUSION: This research
      suggests the importance of parental participation in nutrition education
      interventions in schools. The results contribute to the advancement of knowledge
      in the field and serve as impetus for reflection on how to better direct health
      promotion interventions.

PMID- 25560889
TI  - Youth health care utilization in Nova Scotia: what is the role of age, sex and
      socio-economic status?
AB  - OBJECTIVE: Youth have distinct health care needs that are not always met within a
      framework designed for children or adults. In Canada, little attention has been
      given to how youth utilize health care services and limited data are available.
      The aim of this study was to identify whether age, sex, socio-economic status
      (SES) and geographic location were significant mediators of youth health care
      utilization in Nova Scotia. METHODS: The NSYOUTHS database comprises health care
      utilization information for all youth aged 12 to 24 years, resident in Nova
      Scotia between 1997 and 2007. We calculated health care utilization rates by
      provider, stratified by sex, age, SES, urban/rural residence and year. Negative
      binomial regression was used to model the variation in health care utilization by
      sex, SES and urban/rural location. RESULTS: Health care utilization declined over
      time and varied by age. Females were more frequent users of services. Youth from
      lower SES areas had fewer family physician contacts but more outpatient,
      emergency and inpatient contacts compared to those from higher SES areas. Rural
      residents had fewer family physician and emergency contacts but more outpatient
      contacts than youth from urban areas. Ten percent of the youth were responsible
      for 32% of all health care contacts, whereas 11% had no health care contacts.
      CONCLUSION: Specific subgroups, including youth from rural areas and of lower
      SES, utilize health care services differently than other youth. The challenge is
      to provide health care that is responsive to the needs of this heterogeneous
      population. Meeting this challenge requires accurate information on youth health
      care utilization.

PMID- 25560890
TI  - Differential environmental exposure among non-Indigenous Canadians as a function
      of sex/gender and race/ethnicity variables: a scoping review.
AB  - OBJECTIVES: To determine the extent, range and types of studies of differential
      environmental chemical exposures among non-Indigenous Canadians as a function of
      sex/gender and race/ethnicity. METHODS: Computerized database searches were
      performed from November to December 2013 using Medline, Embase, CAB Abstracts,
      Proquest and Scopus to identify relevant studies of environmental exposures among
      non-Indigenous adults aged >=18 years in Canada published between 1993 and 2013.
      Articles were identified for full-text review based on a screening of titles and
      abstracts and were excluded during this initial review if they focused on
      environmental exposures in the following populations: 1) Indigenous populations,
      2) individuals <15 years of age, 3) pregnant women and associated negative birth
      outcomes, or 4) non-Canadian populations. Articles were also excluded if the
      primary focus was on exposures to environmental tobacco smoke, non-chemical
      occupational hazards, infectious diseases, noise and/or radiation. A full-text
      review of 78 identified articles systematically assessed how sex/gender and
      race/ethnicity were considered. SYNTHESIS: Although 59% of studies stratified
      results by sex, less than half of these offered any explanation of differential
      exposures. Eighteen of the 78 studies (23%) used terms related to race/ethnicity
      in their participant descriptions. Of the studies that conducted subgroup
      analyses of exposure results by race/ethnicity (n=15), a total of 8 also included
      subgroup analysis by sex. Overall, 3 of the 78 (3%) articles reviewed analyzed
      environmental exposures as a function of sex/gender and race/ethnicity.
      CONCLUSION: The role of sex/gender and race/ethnicity in influencing
      environmental exposure levels among non-Indigenous Canadians has not been
      adequately addressed to date.

PMID- 25560891
TI  - Informing body checking policy in youth ice hockey in Canada: a discussion
      meeting with researchers and community stakeholders.
AB  - OBJECTIVES: Body checking is a significant risk factor for injury, including
      concussion, in youth ice hockey. Recent evidence regarding injury rates in youth
      leagues prompted USA Hockey to institute a national policy change in 2011 that
      increased the age of body checking introduction from 11-12 years old (Pee Wee) to
      13-14 years old (Bantam). Body checking policy was more controversial in Canada,
      and research evidence alone was insufficient to drive change. The purpose of this
      paper is to provide an example of one of the knowledge exchange processes that
      occurred between researchers and community stakeholders, leading up to a national
      policy change in 2013. PARTICIPANTS: There were 28 stakeholder attendees,
      representing the research community, youth hockey organizations, and child health
      advocacy groups. SETTING: A one-day meeting held in Whistler, British Columbia,
      in April 2013. INTERVENTION: Researchers and stakeholders presented current
      perspectives on evidence and policy change, and discussion focused on an a priori
      set of questions designed to elicit facilitators and barriers to policy change.
      OUTCOMES: Three major factors that can drive policy change in the sport safety
      context were identified: the need for decision-making leadership, the importance
      of knowledge translation, and the role of sport culture as a barrier to change.
      CONCLUSION: There is a critical need for researcher and stakeholder partnership
      in facilitating ongoing policy discussion and informing evidence-based policy
      change in sport and recreation injury prevention.

PMID- 25560892
TI  - Looking further upstream to prevent fetal alcohol spectrum disorder in Canada.
AB  - Half of all pregnancies in Canada are unintended. Whether a pregnancy is intended
      or unintended has a bearing on the risk of prenatal alcohol exposure. Research
      indicates that women who experience an unintended pregnancy are significantly
      more likely to consume alcohol while pregnant. Most fetal alcohol spectrum
      disorder (FASD) prevention frameworks in Canada have adopted a mid-stream
      approach focused on preventing alcohol consumption among women who are already
      pregnant. Yet there is a second approach, further upstream, that is rarely
      discussed as an FASD prevention tool in this country - preventing unintended
      pregnancy itself. Improving access to long-acting reversible contraceptives for
      women and girls who are experiencing cost and access barriers to these methods
      could do much to stem the incidence of FASD and the prohibitive health and social
      costs associated with this disorder in Canada. 

PMID- 25560893
TI  - Canada Post community mailboxes: implications for health research.
AB  - This article discusses the implications for health research of Canada Post's
      transition from door-to-door postal delivery to community mailboxes. We argue
      that using postal code data to geocode participants based on community mailboxes
      will result in positional and linkage errors. Positional errors involve
      misplacing people's residential location. Linkage errors result from incorrectly
      linking residential location from community mailboxes to census or health
      administrative data. The article discusses examples of how the transition to
      community mailboxes could have important implications for health research. We
      encourage research examining the extent of positional and linkage errors on the
      11 pilot communities transitioning to community mailboxes in the fall of 2014. 

PMID- 25560894
TI  - Problems with the Fraser report Chapter 1: Pitfalls in BMI time trend analysis.
AB  - The first chapter of the Fraser report "Obesity in Canada: Overstated Problems,
      Misguided Policy Solutions" presents a flawed and misleading analysis of BMI time
      trends. The objective of this commentary is to provide a tutorial on BMI time
      trend analysis through the examination of these flaws. Three issues are
      discussed: 1. Spotting regions of confidence interval overlap is a statistically
      flawed method of assessing trend; regression methods which measure the behaviour
      of the data as a whole are preferred. 2. Temporal stability in overweight
      (25<=BMI<30) prevalence must be interpreted in the context of the underlying
      population BMI distribution. 3. BMI is considered reliable for tracking
      population-level weight trends due to its high correlation with body fat
      percentage. BMI-defined obesity prevalence represents a conservative
      underestimate of the population at risk. The findings of the Fraser report
      Chapter 1 are either refuted or substantially mitigated once the above issues are
      accounted for, and we do not find that the 'Canadian situation largely lacks a
      disconcerting or negative trend', as claimed. It is hoped that this commentary
      will help guide public health professionals who need to interpret, or wish to
      perform their own, time trend analyses of BMI.

PMID- 25560895
TI  - Lessons learned and public health's political role: an interview with John Last.

PMID- 25560896
TI  - The pioneer, the activist: an interview with Trevor Hancock.

PMID- 25560897
TI  - Advancing public health skills and structures: an interview with John Frank.

PMID- 25560898
TI  - Increasing public awareness of Ebola virus disease symptoms using a pictogram
      based poster.

PMID- 25560899
TI  - What is the importance of postal codes for health research? Re: (Fuller and
      Shareck) Canada Post community mailboxes: implications for health research.

PMID- 25560900
TI  - Some implications of an event-based definition of exposure to the risk of road
      accident.
AB  - This paper proposes a new definition of exposure to the risk of road accident as
      any event, limited in space and time, representing a potential for an accident to
      occur by bringing road users close to each other in time or space of by requiring
      a road user to take action to avoid leaving the roadway. A typology of events
      representing a potential for an accident is proposed. Each event can be
      interpreted as a trial as defined in probability theory. Risk is the proportion
      of events that result in an accident. Defining exposure as events demanding the
      attention of road users implies that road users will learn from repeated exposure
      to these events, which in turn implies that there will normally be a negative
      relationship between exposure and risk. Four hypotheses regarding the
      relationship between exposure and risk are proposed. Preliminary tests support
      these hypotheses. Advantages and disadvantages of defining exposure as specific
      events are discussed. It is argued that developments in vehicle technology are
      likely to make events both observable and countable, thus ensuring that exposure
      is an operational concept. 

PMID- 25560901
TI  - Calibration of skill and judgment in driving: development of a conceptual
      framework and the implications for road safety.
AB  - Humans often make inflated or erroneous estimates of their own ability or
      performance. Such errors in calibration can be due to incomplete processing,
      neglect of available information or due to improper weighing or integration of
      the information and can impact our decision-making, risk tolerance, and
      behaviors. In the driving context, these outcomes can have important implications
      for safety. The current paper discusses the notion of calibration in the context
      of self-appraisals and self-competence as well as in models of self-regulation in
      driving. We further develop a conceptual framework for calibration in the driving
      context borrowing from earlier models of momentary demand regulation, information
      processing, and lens models for information selection and utilization. Finally,
      using the model we describe the implications for calibration (or, more
      specifically, errors in calibration) for our understanding of driver distraction,
      in-vehicle automation and autonomous vehicles, and the training of novice and
      inexperienced drivers. 

PMID- 25560902
TI  - Cytotoxic effects on tumour cell lines of fatty acids from the marine sponge
      Scopalina ruetzleri.
AB  - OBJECTIVES: Marine sponges are among the most promising sources of chemically
      diversified fatty acids (FAs). In addition, several studies have shown the effect
      of polyunsaturated FAs on cancer therapy. This research carried out a biological
      and chemical evaluation of the sponge Scopalina ruetzleri collected on the South
      Brazilian coastline. METHODS: Bioassay-guided fractionation of S. ruetzleri was
      performed in human glioma (U87) and neuroblastoma (SH-SY5Y) cell lines, and the
      in-vitro effects on free radicals were evaluated. KEY FINDINGS: The ethyl acetate
      fraction of S. ruetzleri showed promising cytotoxic effects in cancer cell lines,
      with IC50  < 20 MUg/ml. Fingerprint (1) H Nuclear Magnetic Resonance (NMR)
      analysis showed that this fraction is mainly constituted of FAs. Through FA
      methyl ester analysis, it was possible to identify 32 FAs. In addition, some
      minor unusual FAs for the marine biosphere were identified. The results of
      conjugated dienes method showed that FAs fraction, at concentrations above 50
      MUg/ml, has a pro-oxidant effect, indicating that lipid peroxidation may be
      partially responsible for the mechanism of cytotoxicity on cancer cells.
      CONCLUSION: This work also contributes to studies that focus on the application
      of FAs on cancer therapy as a new adjuvant to radio or chemotherapy, or as a
      chemotherapeutic agent.

PMID- 25560905
TI  - Microemulsions based on a sunflower lecithin-Tween 20 blend have high capacity
      for dissolving peppermint oil and stabilizing coenzyme Q10.
AB  - The objectives of the present study were to improve the capability of
      microemulsions to dissolve peppermint oil by blending sunflower lecithin with
      Tween 20 and to study the possibility of codelivering lipophilic bioactive
      compounds. The oil loading in microemulsions with 20% (w/w) Tween 20 increased
      from 3% (w/w) to 20% (w/w) upon gradual supplementation of 6% (w/w) lecithin. All
      microemulsions had particles of <12 nm that did not change over 70 d of storage
      at 21  degrees C. They had relatively low Newtonian viscosities and were
      physically and chemically stable after 50-200-fold dilution in water, resulting
      from similar hydrophile-lipophile-balance values of the surfactant mixture and
      peppermint oil. Furthermore, the microemulsions were capable of dissolving
      coenzyme Q10 and preventing its degradation at UV 302 nm, more significant for
      the microemulsion with lecithin. Therefore, natural surfactant lecithin can
      reduce the use of synthetic Tween 20 to dissolve peppermint oil and protect the
      degradation of dissolved lipophilic bioactive components in transparent products.

PMID- 25560903
TI  - Ischaemic conditioning: pitfalls on the path to clinical translation.
AB  - The development of novel adjuvant strategies capable of attenuating myocardial
      ischaemia-reperfusion injury and reducing infarct size remains a major, unmet
      clinical need. A wealth of preclinical evidence has established that ischaemic
      'conditioning' is profoundly cardioprotective, and has positioned the phenomenon
      (in particular, the paradigms of postconditioning and remote conditioning) as the
      most promising and potent candidate for clinical translation identified to date.
      However, despite this preclinical consensus, current phase II trials have been
      plagued by heterogeneity, and the outcomes of recent meta-analyses have largely
      failed to confirm significant benefit. As a result, the path to clinical
      application has been perceived as 'disappointing' and 'frustrating'. The goal of
      the current review is to discuss the pitfalls that may be stalling the successful
      clinical translation of ischaemic conditioning, with an emphasis on concerns
      regarding: (i) appropriate clinical study design and (ii) the choice of the
      'right' preclinical models to facilitate clinical translation.

PMID- 25560904
TI  - Role of adenosine signaling on pentylenetetrazole-induced seizures in zebrafish.
AB  - Adenosine is a well-known endogenous modulator of neuronal excitability with
      anticonvulsant properties. Thus, the modulation exerted by adenosine might be an
      effective tool to control seizures. In this study, we investigated the effects of
      drugs that are able to modulate adenosinergic signaling on pentylenetetrazole
      (PTZ)-induced seizures in adult zebrafish. The adenosine A1 receptor antagonist 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX) decreased the latency to the onset of
      the tonic-clonic seizure stage. The adenosine A1 receptor agonist
      cyclopentyladenosine (CPA) increased the latency to reach the tonic-clonic
      seizure stage. Both the adenosine A2A receptor agonist and antagonist, CGS 21680
      and ZM 241385, respectively, did not promote changes in seizure parameters.
      Pretreatment with the ecto-5'nucleotidase inhibitor adenosine 5'-(alpha,beta
      methylene) diphosphate (AMPCP) decreased the latency to the onset of the tonic
      clonic seizure stage. However, when pretreated with the adenosine deaminase (ADA)
      inhibitor, erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA), or with the nucleoside
      transporter (NT) inhibitors, dipyridamole and S-(4-Nitrobenzyl)-6-thioinosine
      (NBTI), animals showed longer latency to reach the tonic-clonic seizure status.
      Finally, our molecular analysis of the c-fos gene expression corroborates these
      behavioral results. Our findings indicate that the activation of adenosine A1
      receptors is an important mechanism to control the development of seizures in
      zebrafish. Furthermore, the actions of ecto-5'-nucleotidase, ADA, and NTs are
      directly involved in the control of extracellular adenosine levels and have an
      important role in the development of seizure episodes in zebrafish. 

PMID- 25560907
TI  - protonation behavior of histidine during HSF1 activation by physiological
      acidification.
AB  - The expression of eukaryotic molecular chaperones (heat shock proteins, HSPs) is
      triggered in response to a wide range of environmental stresses, including: heat
      shock, hydrogen peroxide, heavy metal, low-pH, or virus infection. Biochemical
      and genetic studies have clearly shown the fundamental roles of heat shock factor
      1 (HSF1) in stress-inducible HSP gene expression, resistance to stress-induced
      cell death, carcinogenesis, and other biological phenomena. Previous studies show
      that acidic pH changes within the physiological range directly activate the HSF1
      function in vitro. However, the detailed mechanism is unclear. Though
      computational pKa-predications of the amino acid side-chain, acidic-pH induced
      protonation of a histidine residue was found to be most-likely involved in this
      process. The histidine 83 (His83) residue, which could be protonated by mild
      decrease in pH, causes mild acidic-induced HSF1 activation (including in-vitro
      trimerization, DNA binding, in-vivo nuclear accumulation, and HSPs expression).
      His83, which is located in the loop region of the HSF1 DNA binding domain, was
      suggested to enhance the intermolecular force with Arginine 79, which helps HSF1
      form a DNA-binding competent. Therefore, low-pH-induced activation of HSF1 by the
      protonation of histidine can help us better to understand the HSF1 mechanism and
      develop more therapeutic applications (particularly in cancer therapy). J. Cell.
      Biochem. 116: 977-984, 2015. (c) 2015 Wiley Periodicals, Inc. 

PMID- 25560911
TI  - Diagnostic clues and manifesting carriers in fukutin-related protein (FKRP) limb
      girdle muscular dystrophy.
AB  - Mutations in the fukutin-related protein (FKRP) gene are a known cause of
      autosomal recessive limb-girdle muscular dystrophy. Clinically, patients resemble
      Becker's muscular dystrophy and generally present in the first two decades of
      life with a mild, progressive phenotype. Cardiac involvement is variable.
      Heterozygous carriers are usually clinically unaffected. We report a patient
      presenting later in life with life-threatening cardiac failure and we describe
      for the first time clinically manifesting carriers in the family. 

PMID- 25560912
TI  - Techno-ecological synergy: a framework for sustainable engineering.
AB  - Even though the importance of ecosystems in sustaining all human activities is
      well-known, methods for sustainable engineering fail to fully account for this
      role of nature. Most methods account for the demand for ecosystem services, but
      almost none account for the supply. Incomplete accounting of the very foundation
      of human well-being can result in perverse outcomes from decisions meant to
      enhance sustainability and lost opportunities for benefiting from the ability of
      nature to satisfy human needs in an economically and environmentally superior
      manner. This paper develops a framework for understanding and designing synergies
      between technological and ecological systems to encourage greater harmony between
      human activities and nature. This framework considers technological systems
      ranging from individual processes to supply chains and life cycles, along with
      corresponding ecological systems at multiple spatial scales ranging from local to
      global. The demand for specific ecosystem services is determined from information
      about emissions and resource use, while the supply is obtained from information
      about the capacity of relevant ecosystems. Metrics calculate the sustainability
      of individual ecosystem services at multiple spatial scales and help define
      necessary but not sufficient conditions for local and global sustainability.
      Efforts to reduce ecological overshoot encourage enhancement of life cycle
      efficiency, development of industrial symbiosis, innovative designs and policies,
      and ecological restoration, thus combining the best features of many existing
      methods. Opportunities for theoretical and applied research to make this
      framework practical are also discussed. 

PMID- 25560913
TI  - Zirconium-catalyzed desymmetrization of aminodialkenes and aminodialkynes through
      enantioselective hydroamination.
AB  - The catalytic addition of alkenes and amines (hydroamination) typically provides
      alpha- or beta-amino stereocenters directly through C-N or C-H bond formation.
      Alternatively, desymmetrization reactions of symmetrical aminodialkenes or
      aminodialkynes provide access to stereogenic centers with the position controlled
      by the substrate's structure. In the present study of an enantioselective
      zirconium-catalyzed hydroamination, stereocenters resulting from C-N bond
      formation and desymmetrization of a prochiral quaternary center are independently
      controlled by the catalyst and reaction conditions. Using a single catalyst, the
      method provides selective access to either diastereomer of optically enriched
      five-, six-, and seven-membered cyclic amines from aminodialkenes and
      enantioselective synthesis of five-, six-, and seven-membered cyclic imines from
      aminodialkynes. Experiments on hydroamination of aminodialkenes testing the
      effects of the catalyst:substrate ratio, the absolute concentration of the
      catalyst, and the absolute initial concentration of the primary amine substrate
      show that the latter parameter strongly influences the stereoselectivity of the
      desymmetrization process, whereas the absolute configuration of the alpha-amino
      stereocenter generated by C-N bond formation is not affected by these parameters.
      Interestingly, isotopic substitution (H2NR vs D2NR) of the substrate enhances the
      stereoselectivity of the enantioselective and diastereoselective processes in
      aminodialkene cyclization and the peripheral stereocenter in aminodialkyne
      desymmetrization/cyclization. 

PMID- 25560914
TI  - Identification, characterization and mycotoxigenic ability of Alternaria spp.
      causing core rot of apple fruit in Greece.
AB  - Alternaria core rot is a major postharvest disease of apple fruit in several
      countries of the world, including Greece. The study was conducted aiming to
      identify the disease causal agents at species level, investigate the
      aggressiveness of Alternaria spp. isolates and the susceptibility of different
      apple varieties and determine the mycotoxigenic potential of Alternaria spp.
      isolates from apple fruit. Seventy-five Alternaria spp. isolates obtained from
      apple fruit showing core rot symptoms were identified as either Alternaria
      tenuissima or Alternaria arborescens at frequencies of 89.3 and 11.7%,
      respectively, based on the sequence of endopolygalacturonase (EndoPG) gene.
      Artificial inoculations of fruit of 4 different varieties (Fuji, Golden
      Delicious, Granny Smith and Red Delicious) and incubation at two different
      temperatures (2 and 25 degrees C) showed that fruit of Fuji variety were the most
      susceptible and fruit of Golden Delicious the most resistant to both pathogens.
      In addition, the production of 3 mycotoxins, alternariol (AOH), alternariol
      monomethyl ether (AME) and tentoxin (TEN) was investigated in 30 isolates of both
      species. Mycotoxin determination was conducted both in vitro, on artificial
      nutrient medium and in vivo on artificially inoculated apple fruit, using a high
      performance liquid chromatography with diode array detector (HPLC-DAD). The
      results showed that most of the isolates of both species were able to produce all
      the 3 metabolites both in vivo and in vitro. On apple fruit A. tenuissima
      isolates produced more AOH than A. arborescens isolates, whereas the latter
      produced more TEN than the former. Such results indicate that Alternaria core rot
      represents a major threat of apple fruit production not only due to quantitative
      yield losses but also for qualitative deterioration of apple by-products. 

PMID- 25560915
TI  - Carvacrol suppresses high pressure high temperature inactivation of Bacillus
      cereus spores.
AB  - The inactivation of bacterial spores generally proceeds faster and at lower
      temperatures when heat treatments are conducted under high pressure, and high
      pressure high temperature (HPHT) processing is, therefore, receiving an increased
      interest from food processors. However, the mechanisms of spore inactivation by
      HPHT treatment are poorly understood, particularly at moderately elevated
      temperature. In the current work, we studied inactivation of the spores of
      Bacillus cereus F4430/73 by HPHT treatment for 5 min at 600MPa in the temperature
      range of 50-100 degrees C, using temperature increments of 5 degrees C.
      Additionally, we investigated the effect of the natural antimicrobial carvacrol
      on spore germination and inactivation under these conditions. Spore inactivation
      by HPHT was less than about 1 log unit at 50 to 70 degrees C, but gradually
      increased at higher temperatures up to about 5 log units at 100 degrees C. DPA
      release and loss of spore refractility in the spore population were higher at
      moderate (<=65 degrees C) than at high (>=70 degrees C) treatment temperatures,
      and we propose that moderate conditions induced the normal physiological pathway
      of spore germination resulting in fully hydrated spores, while at higher
      temperatures this pathway was suppressed and replaced by another mechanism of
      pressure-induced dipicolinic acid (DPA) release that results only in partial
      spore rehydration, probably because spore cortex hydrolysis is inhibited.
      Carvacrol strongly suppressed DPA release and spore rehydration during HPHT
      treatment at <=65 degrees C and also partly inhibited DPA release at >=65 degrees
      C. Concomitantly, HPHT spore inactivation was reduced by carvacrol at 65-90
      degrees C but unaffected at 95-100 degrees C.

PMID- 25560916
TI  - Spherically-clustered porous Au-Ag alloy nanoparticle prepared by partial
      inhibition of galvanic replacement and its application for efficient multimodal
      therapy.
AB  - The polyvinylpyrrolidone (PVP)-coated spherically clustered porous gold-silver
      alloy nanoparticle (PVP-SPAN) was prepared by low temperature mediated, partially
      inhibited galvanic replacement reaction followed by silver etching process. The
      prepared porous nanostructures exhibited excellent photothermal conversion
      efficiency under irradiation of near-infrared light (NIR) and allowed a high
      payload of both doxorubicin (Dox) and thiolated dye-labeled oligonucleotide,
      DNAzyme (FDz). Especially, PVP-SPAN provided 10 times higher loading capacity for
      oligonucleotide than conventional hollow nanoshells due to increased pore
      diameter and surface-to-volume ratio. We demonstrated highly efficient chemo
      thermo-gene multitherapy based on codelivery of Dox and FDz with NIR-mediated
      photothermal therapeutic effect using a model system of hepatitis C virus
      infected human liver cells (Huh7 human hepatocarcinoma cell line containing
      hepatitis C virus NS3 gene replicon) compared to conventional hollow nanoshells. 

PMID- 25560917
TI  - Comparison of trait preferences of Nguni farmers located in semi-arid and sub
      humid environments.
AB  - The objective of the study was to compare trait preferences of Nguni cattle
      owners located in semi-arid and sub-humid environments. Data were collected from
      a total of 300 Nguni cattle-owning households using structured questionnaires,
      150 households from each environment. Stature, body depth and body length were
      preferred more in sub-humid areas than in semi-arid areas. In sub-humid
      environments, preference was given to fertility traits, with farmers more likely
      to highly prefer calving interval and age at first calving (AFC). Semi-arid areas
      had more households with cows with extended calving interval (2 and 3 years) than
      sub-humid areas. Environmental differences affect fertility of Nguni cows and
      trait preferences of communal farmers in Southern Africa. Differences in
      environment and trait preferences of farmers should be considered when designing
      communal breeding programmes. 

PMID- 25560918
TI  - The chromodomain-containing histone acetyltransferase TIP60 acts as a code
      reader, recognizing the epigenetic codes for initiating transcription.
AB  - TIP60 can act as a transcriptional activator or a repressor depending on the
      cellular context. However, little is known about the role of the chromodomain in
      the functional regulation of TIP60. In this study, we found that TIP60 interacted
      with H3K4me3 in response to TNF-alpha signaling. TIP60 bound to H3K4me3 at the
      promoters of the NF-kappaB target genes IL6 and IL8. Unlike the wild-type
      protein, a TIP60 chromodomain mutant did not localize to chromatin regions.
      Because TIP60 binds to histones with specific modifications and transcriptional
      regulators, we used a histone peptide assay to identify histone codes recognized
      by TIP60. TIP60 preferentially interacted with methylated or acetylated histone
      H3 and H4 peptides. Phosphorylation near a lysine residue significantly reduced
      the affinity of TIP60 for the modified histone peptides. Our findings suggest
      that TIP60 acts as a functional link between the histone code and transcriptional
      regulators. 

PMID- 25560919
TI  - Preventive effect of phytic acid on lysosomal hydrolases in normal and
      isoproterenol-induced myocardial infarction in Wistar rats.
AB  - This study was aimed to evaluate the preventive role of phytic acid on lysosomal
      enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar
      rats. Rats subcutaneously injected with ISO (85 mg/kg) at an interval of 24 h for
      two days showed a significant increase in the activities of lysosomal enzymes
      (glucuronidase, N-acetyl glucosaminidase, galactosidase, cathepsin-B and
      cathepsin-D) were increased significantly in serum and the heart of ISO-induced
      rats, but the activities of glucuronidase and cathepsin-D were decreased
      significantly in the lysosomal fraction of the heart. Pretreatment with phytic
      acid (25 and 50 mg/kg) daily for a period of 56 d positively altered activities
      of lysosomal hydrolases in ISO-induced rats. Thus, phytic acid possesses a
      cardioprotective effect in ISO-induced MI in rats. 

PMID- 25560920
TI  - Risk for cerebral palsy in infants with total serum bilirubin levels at or above
      the exchange transfusion threshold: a population-based study.
AB  - IMPORTANCE: Exchange transfusion is recommended for newborns with total serum
      bilirubin (TSB) levels thought to place them at risk for cerebral palsy (CP).
      However, the excess risk for CP among these infants is unknown. OBJECTIVE: To
      quantify the risks for CP and CP consistent with kernicterus that are associated
      with high TSB levels based on the 2004 American Academy of Pediatrics exchange
      transfusion threshold (ETT) guidelines. DESIGN, SETTING, AND PARTICIPANTS: We
      enrolled 2 cohorts from a population of 525,409 infants in the Late Impact of
      Getting Hyperbilirubinemia or Phototherapy (LIGHT) birth cohort. Eligible infants
      were born at a gestational age of at least 35 weeks at 15 hospitals within the
      Kaiser Permanente Northern California integrated medical care delivery system
      from January 1, 1995, through December 31, 2011. EXPOSURES: The exposed cohort
      included all 1833 infants with at least 1 TSB measurement at or above the ETT
      based on age at testing, gestational age, and results of direct antiglobulin
      testing. The unexposed cohort was a 20% random sample of 104 716 infants with TSB
      levels below the ETT. MAIN OUTCOMES AND MEASURES: A pediatric neurologist blinded
      to the TSB levels reviewed medical records to determine the presence of CP,
      defined as a nonprogressive congenital motor dysfunction with hypertonia or
      dyskinesia. Cerebral palsy was judged to be consistent with kernicterus if
      magnetic resonance imaging of the brain revealed bilateral globus pallidus injury
      in the setting of dyskinetic CP. RESULTS: We identified CP in 7 of 1833 exposed
      (0.4%) vs 86 of 104 716 unexposed (0.1%) infants (relative risk, 4.7 [95% CI, 2.2
      10.0]). Absolute risk differences were 0.2% (95% CI, 0%-0.5%) for a TSB level 0
      to 4.9 mg/dL above the ETT (n = 1705), 0.9% (95% CI, 0.1%-5.3%) for a TSB level
      5.0 to 9.9 mg/dL above the ETT (n = 102), and 7.6% (95% CI, 2.1%-24.1%) for a TSB
      level 10 mg/dL or more above the ETT (n = 26). Cerebral palsy consistent with
      kernicterus occurred in 3 infants (incidence, 0.57 per 100,000 births); all 3 had
      TSB levels of more than 5.0 mg/dL above the ETT and at least 2 risk factors for
      neurotoxicity, such as prematurity, glucose-6-phosphate dehydrogenase deficiency,
      or hypoxia-ischemia. CONCLUSIONS AND RELEVANCE: Cerebral palsy consistent with
      kernicterus occurred only in infants with 2 or more risk factors for
      neurotoxicity and TSB levels of more than 5 mg/dL above the ETT. Among infants
      with lower degrees of TSB level elevation, the excess risk for CP is minimal.

PMID- 25560922
TI  - Editorial overview: Host-microbe interactions: bacteria.

PMID- 25560923
TI  - Canine vector-borne co-infections: Ehrlichia canis and Hepatozoon canis in the
      same host monocytes.
AB  - The protozoon Hepatozoon canis and the rickettsia Ehrlichia canis are tick-borne
      pathogens, transmitted by Rhipicephalus sanguineus, which cause canine
      hepatozoonosis and canine monocytic ehrlichiosis, respectively. Co-infection of
      the same host monocytes with H. canis and E. canis confirmed by molecular
      characterization of the infecting agents and quantitative assessment of co
      infected cells is described for the first time in three naturally-infected dogs.
      Blood smear evaluation indicated that at least 50% of the leukocytes infected
      with H. canis gamonts contained E. canis morulae. Co-infection of the same host
      cell demonstrated in this report suggests that infection with one pathogen may
      permit or enhance invasion or prolonged cellular survival of the other. 

PMID- 25560921
TI  - Intertwining of Activin A and TGFbeta Signaling: Dual Roles in Cancer Progression
      and Cancer Cell Invasion.
AB  - In recent years, a significant amount of research has examined the controversial
      role of activin A in cancer. Activin A, a member of the transforming growth
      factor beta (TGFbeta) superfamily, is best characterized for its function during
      embryogenesis in mesoderm cell fate differentiation and reproduction. During
      embryogenesis, TGFbeta superfamily ligands, TGFbeta, bone morphogenic proteins
      (BMPs) and activins, act as potent morphogens. Similar to TGFbetas and BMPs,
      activin A is a protein that is highly systemically expressed during early
      embryogenesis; however, post-natal expression is overall reduced and remains
      under strict spatiotemporal regulation. Of importance, normal post-natal
      expression of activin A has been implicated in the migration and invasive
      properties of various immune cell types, as well as endometrial cells. Aberrant
      activin A signaling during development results in significant morphological
      defects and premature mortality. Interestingly, activin A has been found to have
      both oncogenic and tumor suppressor roles in cancer. Investigations into the role
      of activin A in prostate and breast cancer has demonstrated tumor suppressive
      effects, while in lung and head and neck squamous cell carcinoma, it has been
      consistently shown that activin A expression is correlated with increased
      proliferation, invasion and poor patient prognosis. Activin A signaling is highly
      context-dependent, which is demonstrated in studies of epithelial cell tumors and
      the microenvironment. This review discusses normal activin A signaling in
      comparison to TGFb and highlights how its dysregulation contributes to cancer
      progression and cell invasion. 

PMID- 25560924
TI  - The taxonomic status of Rhipicephalus sanguineus (Latreille, 1806).
AB  - The brown dog tick, Rhipicephalus sanguineus sensu stricto, is a species with
      considerable public health and economic importance. However, the taxonomic status
      of this species is far from resolved. After more than 110 years of scientific
      work on R. sanguineus s.s., the situation is that there is no type, no solid
      description, nor is there a consensus about the range of morphological
      variability within the species. Recent findings based on laboratory crosses and
      molecular genetics strongly suggest that there are several entities grouped under
      the same name. Here we review the history of the taxon, and we point out the
      caveats behind any further work on this tick. The current taxonomic status of R.
      sanguineus s.s. thus lacks an informative original description, and is based on
      the existence of several morphological descriptions based on ticks originating
      from different populations, which show, in some cases, biological incompatibility
      and significant genetic divergence. We suggests that as a result it is not
      possible to assign the specific name R. sanguineus s.s. to any population.
      Further work is required based on the rules issued by the International Code of
      Zoological Nomenclature to clearly define the morphological range of the
      different populations. 

PMID- 25560925
TI  - Infection and Colonization of Several Bermudagrasses by Ophiosphaerella korrae.
AB  - Bermudagrass (Cynodon spp.) is the most commonly used turfgrass in the southern
      United States where it is severely affected by spring dead spot (SDS) caused by
      Ophiosphaerella herpotricha, O. korrae, and O. narmari. In this study, infection
      of bermudagrass roots and stolons by O. korrae was characterized using a
      transformant that expressed the red fluorescent protein tdTomato. Roots of
      interspecific hybrid cultivars Midlawn and Tifway 419, C. transvaalensis
      accessions Uganda and 3200, and C. dactylon cultivar U3 were inoculated and
      observed from 2 to 14 days postinoculation (DPI) while stolons were observed from
      2 to 22 DPI. For all five cultivars tested, a similar level of root colonization
      was observed; however, differences were observed in the rate of necrosis
      development. Necrosis of Tifway 419 and Midlawn tissues was evident at 2 DPI, in
      Uganda and 3200 at 8 DPI, and in U3 necrosis was often absent as late as 14 DPI.
      The fungus rapidly penetrated the root epidermis and colonized the cortex of all
      cultivars by 4 DPI. Colonization of stele tissues by O. korrae was rare in hybrid
      cultivars but common in C. transvaalensis and C. dactylon accessions. On intact
      stolons, the fungus did not penetrate the epidermis 22 DPI though epidermal
      necrosis was evident on the surface of only the hybrid bermudagrasses. Wounded
      stolons became necrotic in all cultivars. Infection and colonization of various
      bermudagrasses by O. korrae was found to be similar to that by O. herpotricha,
      suggesting that host genetic resistance may be used for effective management of
      SDS caused by both species. 

PMID- 25560926
TI  - Transperineal biopsy prostate cancer detection in first biopsy and repeat biopsy
      after negative transrectal ultrasound-guided biopsy: the Victorian Transperineal
      Biopsy Collaboration experience.
AB  - OBJECTIVES: To present the Victorian Transperineal Biopsy Collaboration (VTBC)
      experience in patients with no prior prostate cancer diagnosis, assessing the
      cancer detection rate, pathological outcomes and anatomical distribution of
      cancer within the prostate. PATIENTS AND METHODS: VTBC was established through
      partnership between urologists performing transperineal biopsies of the prostate
      (TPB) at three institutions in Melbourne. Consecutive patients who had TPB, as
      first biopsy or repeat biopsy after previous negative transrectal ultrasound
      guided (TRUS) biopsy, between September 2009 and September 2013 in the VTBC
      database were included. Data for each patient were collected prospectively
      (except for TPB before 2011 in one institution), based on the minimum dataset
      published by the Ginsburg Study Group. Univariate and multivariate analyses were
      used to identify factors predictive of cancer detection on TPB. RESULTS: In all,
      160 patients were included in the study, of whom 57 had TPB as first biopsy and
      103 had TPB as repeat biopsy after previous negative TRUS biopsies. The median
      patient age at TPB was 63 years, with the repeat-biopsy patients having a higher
      median serum PSA level (5.8 ng/mL for first biopsy and 9.6 ng/mL for repeat
      biopsy) and larger prostate volumes (40 mL for first biopsy, and 51 mL for repeat
      biopsy). Prostate cancer was detected in 53% of first-biopsy patients and 36% of
      repeat-biopsy patients, of which 87% and 81%, respectively, were clinically
      significant cancers, defined as a Gleason score of >=7, or more than three
      positive cores of Gleason 6. Of the cancers detected in repeat biopsies, 75%
      involved the anterior region (based on the Ginsburg Study Group's recommended
      biopsy map), while 25% were confined exclusively within the anterior region; a
      lower proportion of only 5% of cancers detected in first biopsies were confined
      exclusively within the anterior region. Age, serum PSA level and prostate volume
      were predictive of cancer detection in repeat biopsies, while only age was
      predictive in first biopsies. CONCLUSIONS: TPB is an alternative approach to TRUS
      biopsy of the prostate, offering a high rate of detection of clinically
      significant prostate cancer. It provides excellent sampling of the anterior
      region of the prostate, which is often under-sampled using the TRUS approach, and
      should be considered as an option for all men in whom a prostate biopsy is
      indicated.

PMID- 25560928
TI  - Synthesis and biological evaluation of nigranoic acid esters as novel human
      neutrophil elastase inhibitors.
AB  - Human neutrophil elastase (HNE) has been implicated as a major contributor in the
      pathogenesis of diseases, such as lung disorders and other inflammatory diseases.
      A series of 12 new nigranoic acid esters were regioselectively synthesised in
      good yields and evaluated for HNE inhibitory activity. Nigranoic acid exhibited
      significant inhibitory activity against HNE with the IC50 value of 3.77 MUM, and
      six esters displayed considerable inhibitory effects on HNE with IC50 values in
      the range of 2.61-8.95 MUM. The nigranoic acid esters having phenyls substituted
      with bromine and trimethoxyls (3h and 3b) showed stronger inhibitory activity on
      HNE than nigranoic acid.

PMID- 25560929
TI  - Stimulating sediment bioremediation with benthic microbial fuel cells.
AB  - Efficient and sustainable technologies for cleaning up of contaminated sediments
      are under urgent demand. Bioremediation by utilizing the natural metabolic
      activities of sediment-inhabited microorganisms has been widely accepted as a
      viable option, but the relatively low efficiency and poor controllability
      severely limite its application. Here, we bring out the concept that
      electrochemical approaches may be used as an efficient means to stimulate
      sediment bioremediation. Although still at the very beginning, benthic microbial
      fuel cells (BMFC) as a remediation technology show many potential benefits, such
      as accelerated decontamination, self-sustained operation, relatively easy
      deployment and control, and environmental benignity. The unique features of BMFC
      setup and operation also give rise to substantially different challenges compared
      to conventional MFCs. In this review, we present a critical overview on the
      characteristics, possible application niches, and state-of-the-art progress of
      this technology. Especially, the current limitations in respect of system design,
      electrode selection, microbial control and selection of deployment environment
      are discussed in details, and the needed future research endeavors to promote its
      practical application are highlighted. 

PMID- 25560927
TI  - Identification and characterization of ML352: a novel, noncompetitive inhibitor
      of the presynaptic choline transporter.
AB  - The high-affinity choline transporter (CHT) is the rate-limiting determinant of
      acetylcholine (ACh) synthesis, yet the transporter remains a largely undeveloped
      target for the detection and manipulation of synaptic cholinergic signaling. To
      expand CHT pharmacology, we pursued a high-throughput screen for novel CHT
      targeted small molecules based on the electrogenic properties of transporter
      mediated choline transport. In this effort, we identified five novel, structural
      classes of CHT-specific inhibitors. Chemical diversification and functional
      analysis of one of these classes identified ML352 as a high-affinity (Ki = 92 nM)
      and selective CHT inhibitor. At concentrations that fully antagonized CHT in
      transfected cells and nerve terminal preparations, ML352 exhibited no inhibition
      of acetylcholinesterase (AChE) or cholineacetyltransferase (ChAT) and also lacked
      activity at dopamine, serotonin, and norepinephrine transporters, as well as many
      receptors and ion channels. ML352 exhibited noncompetitive choline uptake
      inhibition in intact cells and synaptosomes and reduced the apparent density of
      hemicholinium-3 (HC-3) binding sites in membrane assays, suggesting allosteric
      transporter interactions. Pharmacokinetic studies revealed limited in vitro
      metabolism and significant CNS penetration, with features predicting rapid
      clearance. ML352 represents a novel, potent, and specific tool for the
      manipulation of CHT, providing a possible platform for the development of
      cholinergic imaging and therapeutic agents. 

PMID- 25560930
TI  - Biocatalysis for desymmetrization and resolution of stereocenters beyond the
      reactive center: How far is far enough?
AB  - The kinetic resolution of racemates and desymmetrization are the most common
      approaches to the preparation of enantiomerically enriched compounds. These
      procedures allow the access of high valuable, chiral building blocks for many
      purposes in academic or industrial R&D endeavors. Nevertheless, the scope of
      stereochemistry recognition in biotransformations usually occurs at the site of
      the transformation or when it is close to it (not more than 3 bonds). However,
      there are a growing number of enzymatic transformations which surpass the limits
      of stereorecognition of remote chiral (or prochiral) centers. In this account, we
      would like to present some aspects of biocatalyzed remote resolutions and remote
      desymmetrizations to call attention for these challenging transformations. 

PMID- 25560931
TI  - Can laccases catalyze bond cleavage in lignin?
AB  - Modification of lignin is recognized as an important aspect of the successful
      refining of lignocellulosic biomass, and enzyme-assisted processing and upcycling
      of lignin is receiving significant attention in the literature. Laccases (EC
      1.10.3.2) are taking the centerstage of this attention, since these enzymes may
      help degrading lignin, using oxygen as the oxidant. Laccases can catalyze
      polymerization of lignin, but the question is whether and how laccases can
      directly catalyze modification of lignin via catalytic bond cleavage. Via a
      thorough review of the available literature and detailed illustrations of the
      putative laccase catalyzed reactions, including the possible reactions of the
      reactive radical intermediates taking place after the initial oxidation of the
      phenol-hydroxyl groups, we show that i) Laccase activity is able to catalyze bond
      cleavage in low molecular weight phenolic lignin model compounds; ii) For
      laccases to catalyze inter-unit bond cleavage in lignin substrates, the presence
      of a mediator system is required. Clearly, the higher the redox potential of the
      laccase enzyme, the broader the range of substrates, including o- and p
      diphenols, aminophenols, methoxy-substituted phenols, benzenethiols, polyphenols,
      and polyamines, which may be oxidized. In addition, the currently available
      analytical methods that can be used to detect enzyme catalyzed changes in lignin
      are summarized, and an improved nomenclature for unequivocal interpretation of
      the action of laccases on lignin is proposed. 

PMID- 25560932
TI  - New emerging bio-catalysts design in biotransformations.
AB  - The development of new and successful biotransformation processes of key interest
      in medicinal and pharmaceutical chemistry involves creating new biocatalysts with
      improved or even new activities and selectivities. This review emphasizes the new
      emerging developed strategies to achieve this goal, site-selective chemical
      modification of enzymes using tailor-made peptides, specific insertion of metals
      or organometallic complexes into proteins producing bio-catalysts with multiple
      activities and computational design for creating evolved artificial enzymes with
      non-natural synthetic catalytic activities. 

PMID- 25560933
TI  - CaMoDi: a new method for cancer module discovery.
AB  - BACKGROUND: Identification of genomic patterns in tumors is an important problem,
      which would enable the community to understand and extend effective therapies
      across the current tissue-based tumor boundaries. With this in mind, in this work
      we develop a robust and fast algorithm to discover cancer driver genes using an
      unsupervised clustering of similarly expressed genes across cancer patients.
      Specifically, we introduce CaMoDi, a new method for module discovery which
      demonstrates superior performance across a number of computational and
      statistical metrics. RESULTS: The proposed algorithm CaMoDi demonstrates
      effective statistical performance compared to the state of the art, and is
      algorithmically simple and scalable - which makes it suitable for tissue
      independent genomic characterization of individual tumors as well as groups of
      tumors. We perform an extensive comparative study between CaMoDi and two
      previously developed methods (CONEXIC and AMARETTO), across 11 individual tumors
      and 8 combinations of tumors from The Cancer Genome Atlas. We demonstrate that
      CaMoDi is able to discover modules with better average consistency and
      homogeneity, with similar or better adjusted R2 performance compared to CONEXIC
      and AMARETTO. CONCLUSIONS: We present a novel method for Cancer Module Discovery,
      CaMoDi, and demonstrate through extensive simulations on the TCGA Pan-Cancer
      dataset that it achieves comparable or better performance than that of CONEXIC
      and AMARETTO, while achieving an order-of-magnitude improvement in computational
      run time compared to the other methods.

PMID- 25560934
TI  - Quality control of residual solvent content in polymeric microparticles.
AB  - Organic solvents are the innate part of pharmaceutical industry, playing vital
      role in the bulk drug substance as well as finished product manufacturing. Even
      though they are used for various crucial purposes, they still lack therapeutic
      beneficial effect and can be toxic if present in unacceptable limits in final
      product. Hence, their concentration must be regulated in the final pharmaceutical
      formulation. With the major development in the market of polymeric microparticles
      in past few decades, drug product manufacturers are paying more attention towards
      the development of new techniques for reducing residual solvent content of
      microparticles. This article sheds light on the importance of removal of organic
      volatile impurities from the formulation and its regulatory aspects. It also
      highlights how residual solvent affects various physicochemical characteristics
      of polymeric microparticles and suggests certain solutions as per the current
      state of art for limiting organic solvent content in the final product. 

PMID- 25560935
TI  - Skyrmion-skyrmion and skyrmion-edge repulsions in skyrmion-based racetrack
      memory.
AB  - Magnetic skyrmions are promising for building next-generation magnetic memories
      and spintronic devices due to their stability, small size and the extremely low
      currents needed to move them. In particular, skyrmion-based racetrack memory is
      attractive for information technology, where skyrmions are used to store
      information as data bits instead of traditional domain walls. Here we numerically
      demonstrate the impacts of skyrmion-skyrmion and skyrmion-edge repulsions on the
      feasibility of skyrmion-based racetrack memory. The reliable and practicable
      spacing between consecutive skyrmionic bits on the racetrack as well as the
      ability to adjust it are investigated. Clogging of skyrmionic bits is found at
      the end of the racetrack, leading to the reduction of skyrmion size. Further, we
      demonstrate an effective and simple method to avoid the clogging of skyrmionic
      bits, which ensures the elimination of skyrmionic bits beyond the reading
      element. Our results give guidance for the design and development of future
      skyrmion-based racetrack memory. 

PMID- 25560937
TI  - Do extreme values of daily-life gait characteristics provide more information
      about fall risk than median values?
AB  - BACKGROUND: Gait characteristics estimated from daily-life trunk accelerations
      reflect gait quality and are associated with fall incidence in older adults.
      While associations are based on median values of these gait characteristics,
      their extreme values may reflect either high-risk situations or steady-state gait
      and may thus be more informative in relation to fall risk. OBJECTIVE: The
      objective of this study was to improve fall-risk prediction models by examining
      whether the use of extreme values strengthens the associations with falls.
      METHODS: Trunk acceleration data (Dynaport MoveMonitor) were collected from 202
      older adults over a full week. From all walking episodes, we estimated the median
      and, as reliable estimates of the extremes, the 10th and 90th percentiles of gait
      characteristics, all over 10-second epochs. In addition, the amount of daily
      activities was derived from the acceleration data, and participants completed
      fall-risk questionnaires. Participants were classified as fallers based on one or
      more falls during 6 months of follow-up. Univariate analyses were performed to
      investigate whether associations with falls were stronger for the extremes than
      for the medians. Subsequently, three fall-risk models were compared: (1) using
      questionnaire data only, (2) adding the amount of activities and medians of gait
      characteristics, and (3) using extreme values instead of medians in the case of
      stronger univariate associations of the extremes. RESULTS: Stronger associations
      were found for the extreme characteristics reflecting high regularity, low
      frequency variability, and low local instability in anterior-posterior direction,
      for high symmetry in all directions and for low entropy in anterior-posterior and
      vertical directions. The questionnaire-only model improved significantly by
      adding activities and gait characteristics' medians. Replacing medians by
      extremes with stronger associations did improve the fall prediction model, but
      not significantly. CONCLUSIONS: Associations were stronger for extreme values,
      indicating "high gait quality" situations (ie, 10th and 90th percentiles in case
      of positive and negative associations, respectively) and not for "low gait
      quality" situations. This suggests that gait characteristics during optimal
      performance gait provide more information about the risk of falling than high
      risk situations. However, their added value over medians in prediction is
      limited.

PMID- 25560938
TI  - Psychosis and cardiovascular disease: is diet the missing link?
AB  - OBJECTIVE: To explore the diets of people living with psychotic disorders, and to
      compare their dietary composition to the general population. METHOD: 184 people
      with psychotic disorders in Adelaide, South Australia completed a food frequency
      questionnaire. Physical information and mental health status were collected.
      Outcome measures included energy and macronutrient intake; fish, sodium, fruit
      and vegetable intake; micro-nutrient intake; body mass index; waist
      circumference; and diagnoses of diabetes and hypertension. The RDI of nutrients
      was derived from Australian Government publications. Comparison dietary data was
      obtained from surveys carried out by the Australian Bureau of Statistics.
      RESULTS: The majority of participants were overweight or obese (78%) and 77.5%
      met the criteria for at-risk waist circumference; and 58% of participants
      consumed salt and saturated fat in excess of the RDI. Most did not achieve the
      RDI for fruits and vegetables (97.8%), fibre (88.6%), fish (61.4%), magnesium
      (73.4%) or folate (86.4%). Women with psychosis had significantly higher intakes
      of vitamins and minerals compared to women in the general population. Men and
      women with psychosis consumed more daily total fat, saturated fat and sodium
      compared to adults in the Australian population, but lower fibre and vitamin E
      than their male and female counterparts. CONCLUSION: People with psychosis,
      especially women, report poor dietary choices including increased energy and fat
      intake, heightening their risk for cardiovascular disease. Women with psychosis
      report higher intake of vitamins and minerals than women in the general
      population. Whilst dietary intake contributes to obesity in psychosis, other
      factors including antipsychotic agents, decreased physical activity and smoking
      add to the cardiovascular risk.

PMID- 25560936
TI  - Epigenetics and memory: causes, consequences and treatments for post-traumatic
      stress disorder and addiction.
AB  - Understanding the interaction between fear and reward at the circuit and
      molecular levels has implications for basic scientific approaches to memory and
      for understanding the etiology of psychiatric disorders. Both stress and exposure
      to drugs of abuse induce epigenetic changes that result in persistent behavioral
      changes, some of which may contribute to the formation of a drug addiction or a
      stress-related psychiatric disorder. Converging evidence suggests that similar
      behavioral, neurobiological and molecular mechanisms control the extinction of
      learned fear and drug-seeking responses. This may, in part, account for the fact
      that individuals with post-traumatic stress disorder have a significantly
      elevated risk of developing a substance use disorder and have high rates of
      relapse to drugs of abuse, even after long periods of abstinence. At the
      behavioral level, a major challenge in treatments is that extinguished behavior
      is often not persistent, returning with changes in context, the passage of time
      or exposure to mild stressors. A common goal of treatments is therefore to weaken
      the ability of stressors to induce relapse. With the discovery of epigenetic
      mechanisms that create persistent molecular signals, recent work on extinction
      has focused on how modulating these epigenetic targets can create lasting
      extinction of fear or drug-seeking behavior. Here, we review recent evidence
      pointing to common behavioral, systems and epigenetic mechanisms in the
      regulation of fear and drug seeking. We suggest that targeting these mechanisms
      in combination with behavioral therapy may promote treatment and weaken stress
      induced relapse. 

PMID- 25560940
TI  - Chemical stimulation of the lateral hypothalamus by carbachol attenuated the
      formalin-induced pain behaviors in rats.
AB  - Electrical and chemical stimulation of the lateral hypothalamus (LH) produces
      analgesia. Previous studies emphasized the importance of LH in the modulation of
      nociceptive behaviors in the acute pain models. In the current study, for the
      first time, we examined the effect of direct chemical stimulation of the LH with
      cholinergic receptor agonist, carbachol, on pain-related behaviors in the
      formalin test as a model of persistent inflammatory pain. Forty-eight adult male
      Wistar rats were implanted unilaterally with cannula into the LH. Four doses of
      carbachol (62.5, 125, 250 and 500 nM/0.5 MUl saline) were microinjected into the
      LH just 5 min before the formalin test. Vehicle group received 0.5 MUl saline
      into the LH. Pain-related behaviors were quantified and monitored in 5-min blocks
      for 60 min test period. Average nociceptive scores and area under the curve (AUC)
      as raw pain scores * time by the linear trapezoidal method were used for the
      statistical analyses. One important finding of our study was that carbachol
      blocks the nociceptive responses in both phases of formalin-induced nociception
      in a dose-dependent manner. Altogether, the percentage decrease of AUC values
      calculated for treatment groups, compared to the control group, was more
      significant in the late phase than the early phase. These findings suggest that
      LH modulates formalin-induced nociception through spinal and/or supraspinal
      sites.

PMID- 25560939
TI  - Differential expression of the beta4 neuronal nicotinic receptor subunit affects
      tolerance development and nicotinic binding sites following chronic nicotine
      treatment.
AB  - The role of neuronal nicotinic acetylcholine receptors (nAChR) containing the
      beta4 subunit in tolerance development and nicotinic binding site levels
      following chronic nicotine treatment was investigated. Mice differing in
      expression of the beta4-nAChR subunit [wild-type (beta4(++)), heterozygote
      (beta4(+-)) and null mutant (beta4(--))] were chronically treated for 10 days
      with nicotine (0, 0.5, 1.0, 2.0 or 4.0mg/kg/h) by constant intravenous infusion.
      Chronic nicotine treatment elicited dose-dependent tolerance development. beta4(-
      ) mice developed significantly more tolerance than either beta4(++) or beta4(+-)
      mice which was most evident following treatment with 4.0mg/kg/h nicotine. Subsets
      of [(125)I]-epibatidine binding were measured in several brain regions. Deletion
      of the beta4 subunit had little effect on initial levels of cytisine-sensitive
      [(125)I]-epibatidine binding (primarily alpha4beta2-nAChR sites) or their
      response (generally increased binding) to chronic nicotine treatment. In
      contrast, beta4 gene-dose-dependent decreases in expression 5IA-85380 resistant
      [(125)I]-epibatidine binding sites (primarily beta4*-nAChR) were observed. While
      these beta4*-nAChR sites were generally resistant to regulation by chronic
      nicotine treatment, significant increases in binding were noted for habenula and
      hindbrain. Comparison of previously published tolerance development in beta2(--)
      mice (less tolerance) to that of beta4(--) mice (more tolerance) supports a
      differential role for these receptor subtypes in regulating tolerance following
      chronic nicotine treatment.

PMID- 25560944
TI  - Do not throw out the resveratrol with the bath water.

PMID- 25560945
TI  - Left ventricular noncompaction and athletes: looking for stratification criteria.

PMID- 25560941
TI  - Chronic high-dose creatine has opposing effects on depression-related gene
      expression and behavior in intact and sex hormone-treated gonadectomized male and
      female rats.
AB  - Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism
      shown to improve depressive symptoms in humans and animals, especially in
      females. To better understand the pharmacological effects of creatine, we
      examined its influence on depression-related hippocampal gene expression and
      behaviors in the presence and absence of sex steroids. Sham-operated and
      gonadectomized male and female rats were fed chow alone or chow blended with
      either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open
      field, and wire suspension tests, or seven weeks total. Before supplementation,
      males were chronically implanted with an empty or a testosterone-filled (T)
      capsule (10-mm surface release), and females were administered progesterone (P,
      250 MUg), estradiol benzoate (EB, 2.5 MUg), EB+P, or sesame oil vehicle weekly.
      Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs
      measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B,
      doublecortin, calretinin, and calbindin, were downregulated in sham males given
      4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in
      sham females given 4% creatine. In contrast, combined 4% creatine+T in castrates
      prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly,
      combined 4% creatine+EB+P in ovariectomized females attenuated downregulation of
      BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like
      behaviors were observed in EB+P-treated ovariectomized females fed creatine, with
      similar trends in T-treated castrates fed creatine. Altogether, these data show
      that chronic, high-dose creatine has opposing effects on neuroplasticity-related
      genes and depressive behavior in intact and gonadectomized male and female rats.
      The dose and schedule of creatine used negatively impacted hippocampal neuronal
      integrity in otherwise healthy brains, possibly through negative compensatory
      changes in energy metabolism, whereas combined creatine and sex steroids acted in
      a neuroprotective manner in gonadectomized rats, potentially by reducing
      metabolic complications associated with castration or ovariectomy.

PMID- 25560946
TI  - Criteria for waiver of informed consent for quality improvement research.

PMID- 25560947
TI  - Left ventricular noncompaction and athletes-reply.

PMID- 25560948
TI  - Is there more than just 1 ethical standard for clinical trials?

PMID- 25560949
TI  - Criteria for waiver of informed consent for quality improvement research-reply.

PMID- 25560950
TI  - Faster brain shrinkage in the ACCORD MIND study: an unexpected result?

PMID- 25560951
TI  - Faster brain shrinkage in the ACCORD MIND study-reply.

PMID- 25560952
TI  - Why are we consuming so much sugar despite knowing too much can harm us?

PMID- 25560953
TI  - Why are we consuming so much sugar despite knowing too much can harm us?-Reply.

PMID- 25560954
TI  - Building continuity in handovers with shorter residency duty hours.
AB  - As junior doctors work shorter hours in light of concerns about the harmful
      effects of fatigue on physician performance and health, it is imperative to
      consider how to ensure that patient safety is not compromised by breaks in the
      continuity of care. By reconceptualizing handover as a necessary bridge to
      continuity, and hence to safer patient care, the model of continuity-enhanced
      handovers has the potential to allay fears and improve patient care in an era of
      increasing fragmentation. "Continuity-enhanced handovers" differ from traditional
      handovers in several key aspects, including quality of information transferred,
      greater professional responsibility of senders and receivers, and a different
      philosophy of "coverage." Continuity during handovers is often achieved through
      scheduling and staffing to maximize the provision of care by members of the
      primary team who have first-hand knowledge of patients. In this way, senders and
      receivers often engage in intra-team handovers, which can result in the
      accumulation of greater common ground or shared understanding of the patients
      they collectively care for through a series of repeated interactions. However,
      because maximizing team continuity is not always possible, other strategies such
      as cultivating high-performance teams, making handovers active learning
      opportunities, and monitoring performance during handovers are also important.
      Medical educators and clinicians should work toward adopting and testing
      principles of continuity-enhanced handovers in their local practices and share
      successes so that innovation and learning may spread easily among institutions
      and practices. 

PMID- 25560956
TI  - Functional acetabular orientation varies between supine and standing radiographs:
      implications for treatment of femoroacetabular impingement.
AB  - BACKGROUND: Often, anteroposterior (AP) pelvic radiographs are performed with the
      patient positioned supine. However, this may not represent the functional
      position of the pelvis and the acetabulum, and so when assessing patients for
      conditions like femoroacetabular impingement (FAI), it is possible that standing
      radiographs better incorporate the dynamic influences of periarticular
      musculature and sagittal balance. However, this thesis remains largely untested.
      QUESTIONS/PURPOSES: The purpose of this study was to determine the effect of
      supine and standing pelvic orientation on (1) measurements of acetabular version
      and common radiographic signs of FAI as assessed on two- and three-dimensional (3
      D) imaging; and (2) on terminal hip range of motion (ROM). METHODS: Preoperative
      pelvic CT scans of 50 patients (50 hips) who underwent arthroscopic surgery for
      the treatment of FAI between July 2013 and October 2014 were analyzed. The mean
      age of the study population was 29 +/- 10 years (range, 15-50 years) and 70% were
      male. All patients had a standing AP pelvis radiograph, a reconstructed supine
      radiograph from the CT data, and a 3-D model created to allow manipulation of
      pelvic tilt and simulate ROM to osseous contact. Acetabular version was measured
      and the presence of the crossover sign, prominent ischial spine sign, and
      posterior wall sign were recorded on simulated plain radiographs. Measurements of
      ROM to bony impingement were made during (1) simulated hip flexion; (2) simulated
      internal rotation in 90 degrees  of flexion (IRF); and (3) simulated internal
      rotation in 90 degrees  of flexion and 15 degrees  adduction (FADIR), and the
      location of bony contact between the proximal femur and acetabular rim was
      defined. These measurements were calculated for supine and standing pelvic
      orientations. A paired Student's t-test was used for comparison of continuous
      variables, whereas chi square testing was used for categorical variables. A p
      value of < 0.05 was considered significant. RESULTS: When changing from supine to
      the standing radiographs, both mean cranial and central version increased by 2
      degrees  +/- 4 degrees  (95% confidence interval [CI], 1 degrees -3 degrees ) and
      2 degrees  +/- 3 degrees  (95% CI, 1 degrees -3 degrees ), respectively (both p <
      0.001). However, with the numbers available, there were no changes in the
      proportion of positive crossover, posterior wall, and prominent ischial spine
      signs. Standing pelvic position tilt resulted in an increased hip flexion of 3
      degrees  (95% CI, 2 degrees -4 degrees ) as well as an increase in IRF of 2
      degrees  (95% CI, 1 degrees -3 degrees ) and FADIR of 3 degrees  (95% CI, 2
      degrees -4 degrees ) (all p < 0.001). CONCLUSIONS: The functional orientation of
      the acetabulum varies between supine and standing radiographs and must be
      considered when diagnosing and treating patients with symptomatic FAI. Standing
      pelvic orientation results in posterior pelvic tilt and later occurrence of FAI
      in the arc of motion. Although we cannot recommend standing radiographs on the
      current study alone, we do recommend larger studies to determine whether any
      significant differences truly exist.

PMID- 25560957
TI  - Metal-on-conventional polyethylene total hip arthroplasty bearing surfaces have a
      higher risk of revision than metal-on-highly crosslinked polyethylene: results
      from a US registry.
AB  - BACKGROUND: Although studies have reported lower radiological wear in highly
      crosslinked polyethylene (HXLPE) versus conventional polyethylene in total hip
      arthroplasty (THA), there is limited clinical evidence on the risk of revision of
      these polyethylene THA bearing surfaces. QUESTIONS/PURPOSES: We asked: (1) Do
      primary THAs with a metal-on-conventional polyethylene bearing surface have a
      higher risk of revision (all-cause or aseptic) than metal-on-HXLPE? (2) Is the
      risk of revision (all-cause or aseptic) higher for conventional polyethylene
      versus HXLPE when the effect of femoral and acetabular components is controlled
      for in prosthesis-specific analyses? METHODS: The Kaiser Permanente's Total Joint
      Replacement Registry was used to identify metal-on-conventional polyethylene and
      metal-on-HXLPE primary THAs (N = 26,823) performed between April 2001 and
      December 2011. The registry has 95% voluntary participation and 8% were lost to
      followup during the 10-year study period. Endpoints of interest were all-cause
      and aseptic revisions. Descriptive statistics and marginal Cox regression models
      with propensity score adjustments were applied to compare risk of revision for
      metal-on-conventional polyethylene versus metal-on-HXLPE THAs and to evaluate two
      specific manufacturers' hip implant designs while controlling for femoral and
      acetabular components. Of the 26,823 THAs included in the study, 1815 (7%) were
      metal-on-conventional polyethylene and 25,008 (93%) were metal-on-HXLPE. RESULTS:
      At 7 years followup, the cumulative incidence of revision was 5.4% (95%
      confidence interval [CI], 4.4%-6.7%) for metal-on-conventional and 2.8% (95% CI,
      2.6%-3.2%) for metal-on-HXLPE. There was a higher adjusted risk of all-cause
      (hazard ratio [HR], 1.75; 95% CI, 1.37-2.24; p < 0.001) and aseptic (HR, 1.91;
      95% CI, 1.46-2.50; p < 0.001) revisions among metal-on-conventional polyethylene
      bearing surface hips compared with metal-on-HXLPE. Results were similar within
      manufacturer hip designs with the same femoral and acetabular components.
      Conclusions Metal-on-conventional polyethylene THA bearing surfaces have a higher
      risk of revision compared with metal-on-HXLPE bearing surfaces. Clinicians should
      consider the use of HXLPE when using a polyethylene bearing in THA. LEVEL OF
      EVIDENCE: Level II, cohort study.

PMID- 25560955
TI  - Topical tranexamic Acid does not affect electrophysiologic or neurovascular
      sciatic nerve markers in an animal model.
AB  - BACKGROUND: Tranexamic acid is a safe and effective antifibrinolytic agent used
      systemically and topically to reduce blood loss and transfusion rate in patients
      having TKA or THA. As the hip does not have a defined capsule, topical
      application of tranexamic acid may entirely envelop the sciatic nerve during THA.
      Accidental application of tranexamic acid onto the spinal cord in spinal
      anesthesia has been shown to produce seizures; therefore, we sought to
      investigate if topical application of tranexamic acid on the sciatic nerve has a
      deleterious effect. QUESTIONS/PURPOSES: We explored whether there were any short-
      or long-term alterations in (1) electrophysiologic measures, (2) macrophage
      recruitment, or (3) blood-nerve barrier permeability. Our hypothesis was that
      local application of tranexamic acid would have a transient effect or no effect
      on histologic features and function of the sciatic nerve. METHODS: We used a rat
      protocol to model sciatic nerve exposure in THA to determine the effects of
      tranexamic acid on neural histologic features and function. We evaluated 35 rats
      by the dorsal gluteal splitting approach to expose the sciatic nerve for topical
      use of control and tranexamic acid. We evaluated EMG changes (distal latency,
      amplitude, nerve conduction velocity), histologic signs of nerve injury via
      macrophage recruitment, and changes in blood-nerve barrier permeability at early
      (4 days) and late (1 month) times after surgery, after application of
      subtherapeutic (1 mg/kg body weight [1.6 mg]), therapeutic (10 mg/kg [16 mg]),
      and supratherapeutic (100 mg/kg [160 mg]) concentrations of tranexamic acid.
      Differences in blood-nerve barrier permeability, macrophage recruitment, and EMG
      between normal and tranexamic acid-treated nerves were calculated using one-way
      ANOVA, with Newman-Keuls post hoc analyses, at each time. A post hoc power
      calculation showed that with the numbers available, we had 16% power to detect a
      50% difference in EMG changes between the control, 1 mg/kg group, 10 mg/kg group,
      and 100 mg/kg group. RESULTS: At the early and late times, with the numbers
      available, there were no differences in EMG except for distal latency at 4 days,
      macrophage recruitment, or changes in blood-nerve barrier between control rats
      and those with tranexamic acid-treated nerves. The distal latency in the 1 mg
      tranexamic acid-treated animals at 4 days was 1.06 +/- 0.15 ms (p = 0.0036 versus
      all other groups, 95% CI, 0.89-1.25), whereas the distal latencies in the
      control, the 10 mg/kg, and 100 mg/kg tranexamic acid-treated animals were 0.83 +/
      0.11, 0.89 +/- 0.05, and 0.87 +/- 0.13, respectively. Distal latencies were not
      increased in any of the groups at 1 month with the numbers available (0.81 +/-
      0.10, 0.89 +/- 0.03, 0.81 +/- 0.06, and 0.83 +/- 0.08 ms, respectively, for
      controls; 1 mg/kg, 10 mg/kg, and 100 mg/kg for the tranexamic acid-treated
      groups). CONCLUSION: In our in vivo rat model study, tranexamic acid did not
      appear to have any clinically relevant effect on the sciatic nerve resulting from
      topical administration up to 1 month. However, because our statistical power was
      low, these data should be considered hypothesis-generating pilot data for larger,
      more-definitive studies. CLINICAL RELEVANCE: Topical tranexamic acid is effective
      in decreasing patient blood loss during THA, and results from our in vivo rat
      model study suggest there may be no electrophysiologic and histologic effects on
      the sciatic nerve, with the numbers available, up to 1 month.

PMID- 25560958
TI  - Short-term complications have more effect on cost-effectiveness of THA than
      implant longevity.
AB  - BACKGROUND: Outcomes research in THA has focused largely on long-term implant
      survivorship as a primary outcome and emphasized the development of new implant
      technologies. In contrast, strategies to improve short-term outcomes, such as the
      frequencies of periprosthetic joint infections and unplanned readmissions, have
      received less attention. QUESTIONS/PURPOSES: We asked whether reductions in
      periprosthetic joint infections and early readmissions would have greater
      influence on the net monetary benefit (a summation of lifetime cost and quality
      of life) for THA compared with equivalent reductions in aseptic loosening.
      METHODS: A Markov model was created using decision-analysis software with six
      health states and death to represent seven major potential outcomes of THA. We
      compared the effect of a 10% reduction in each of the following outcomes: (1)
      periprosthetic joint infection, (2) hospital readmission, and (3) aseptic
      loosening. Procedure costs (not charges) were derived from our hospital cost
      accounting system. Probabilities were derived primarily from the Australian
      Orthopaedic Association National Joint Replacement Registry, and utilities were
      estimated from a previous study at our institution using the time trade-off
      method. The primary outcome of the study is the net monetary benefit, which
      combines the reductions in cost and improvement in health-related quality of life
      in a single metric. Quality of life is expressed in quality-adjusted life years
      (QALYs), which are calculated by multiplying the utility of a health state
      (ranging from 0 to 1) by the duration of time in the health state. The cost and
      QALYs are reported separately as secondary outcomes. One-way and multivariate
      sensitivity analyses were performed including a probabilistic sensitivity
      analysis to account for uncertainty in model inputs. RESULTS: The net monetary
      benefit for a 10% reduction in periprosthetic joint infections was USD 278 (95%
      CI, USD 239-295) per index procedure compared with USD 174 (95% CI, USD 150-185)
      and USD 113 (95% CI, USD 94-129) for reductions in aseptic loosening and early
      readmission, respectively. Compared with the base case, reductions in cost
      associated with a 10% reduction in periprosthetic joint infections, early
      readmissions, and aseptic loosening were USD 98, USD 93, and USD 75 per index
      procedure, respectively. The increase in QALYs for an equivalent reduction in
      periprosthetic joint infections, aseptic loosening, and early readmissions were
      0.0036, 0.002, and 0.0004 QALYs, respectively. Results were most sensitive to
      age, baseline rate of readmission, periprosthetic joint infection, aseptic
      loosening, and the costs of readmission and revision THA. CONCLUSIONS: Strategies
      to reduce periprosthetic joint infections may have a greater effect on the cost
      and long-term effectiveness of THA than further enhancements in implant
      longevity. Reductions in the rate of readmission resulted in greater reductions
      in cost but not quality-of-life, and therefore had smaller effect on the net
      monetary benefit compared with aseptic loosening. Surgeons preferentially should
      engage in strategies focusing on periprosthetic joint infections to improve the
      value of THA care. LEVEL OF EVIDENCE: Level II, economic and decision analysis.

PMID- 25560959
TI  - Does previous pelvic osteotomy compromise the results of periacetabular osteotomy
      surgery?
AB  - BACKGROUND: As the Bernese periacetabular osteotomy (PAO) has grown in
      popularity, specific indications and the results in patients treated for those
      indications need to be evaluated. Currently, although many patients undergo PAO
      after having had prior pelvic osteotomy, there is limited information regarding
      the efficacy of the PAO in these patients. QUESTIONS/PURPOSES: The purpose of
      this study was to compare the (1) early pain, function, activity, and quality of
      life outcomes; (2) radiographic correction; and (3) major complications and
      failures between patients who underwent PAO after prior pelvic reconstruction
      versus those who had a PAO without prior surgery. METHODS: Between February 2008
      and January 2012, 39 patients underwent PAO after prior pelvic osteotomy at one
      of 11 centers and were entered into a collaborative multicenter database. Of
      those, 34 (87%) were available for followup at a mean of 2.5 years (range 1-5
      years). This group was compared with a matched group of 78 subjects, of whom 71
      (91%) were available for followup at a similar interval. We compared clinical
      outcomes including UCLA activity score, SF-12, and Hip Disability and
      Osteoarthritis Outcome Score (HOOS); radiographic measures-anterior and lateral
      center-edge angle and acetabular inclination (AI)-and reoperations, major
      complications, and conversions to total hip arthroplasty. RESULTS: Although both
      groups reached clinical improvement in all categorical measures, the revision PAO
      group demonstrated greater pain (HOOS pain, study 74 versus 85, p = 0.03; 95%
      confidence interval [CI], 18.58 to -0.95) and less function (HOOS activities of
      daily living, study 80 versus 92, p = 0.002; 95% CI, 018.99-4.45) than the
      primary cohort. The revision cohort achieved a smaller average radiographic
      correction than in patients undergoing PAO without prior pelvic surgery. The mean
      correction in AI was less dramatic when directly comparing the revision and
      comparison groups (-12 degrees  to -17 degrees , p < 0.001, SD 2.3-8.5). Although
      there was no difference in severe complications requiring further surgery, there
      were two conversions to hip arthroplasty (p = 0.109; 95% CI, 0.004-2.042) in the
      study group. CONCLUSIONS: PAO performed after prior pelvic surgery is associated
      with improvements in pain, function, radiographic correction, and early
      complication rates, but the improvements observed at short-term followup were
      smaller and more variable than those seen in patients who had not undergone prior
      pelvic surgery. We recommend considering PAO for residual deformities after prior
      osteotomy to improve function and quality life but warning patients of potential
      ceiling effects with a second periacetabular surgery.

PMID- 25560960
TI  - Does surgical hip dislocation and periacetabular osteotomy improve pain in
      patients with Perthes-like deformities and acetabular dysplasia?
AB  - BACKGROUND: Patients with symptomatic residual Perthes-like deformities may
      present with a combination of structural abnormalities including a large aspheric
      femoral head, short and wide femoral neck, high greater trochanter, and
      acetabular dysplasia. Sometimes, the hip is further compromised by concurrent
      symptomatic femoroacetabular impingement (FAI) (proximal femoral deformities) and
      structural instability (acetabular dysplasia). QUESTIONS/PURPOSES: We therefore
      sought to characterize (1) the intraoperative findings; (2) radiographic
      correction; and (3) early patient-reported outcomes, complications, and failures
      of treating complex Perthes-like hip deformities with combined surgical
      dislocation and periacetabular osteotomy (PAO). METHODS: We performed 694 hip
      preservation procedures between November 2006 and August 2010. Of these, 46 had
      residual Perthes-like hip deformities, defined as proximal deformity consistent
      with residual Perthes and a history of Perthes disease or treatment of pediatric
      hip dysplasia. Of these, we report on 16 patients (16 hips) with residual Perthes
      like hip deformities and associated acetabular dysplasia (structural instability,
      defined as radiographic evidence of acetabular dysplasia with intraoperative
      confirmation of instability). These 16 patients were treated with a combined
      surgical hip dislocation to comprehensively address intraarticular and
      extraarticular sources of FAI and PAO to address structural instability and were
      analyzed at a minimum 24-month followup (median, 40 months; range, 24-78 months).
      No patients in this series were lost to followup. Ten patients' hips had previous
      surgical treatment, including six with previous osteotomy. Operative findings
      were extracted from standardized prospectively collected intraoperative data
      collection forms. Radiographic correction was evaluated with established methods
      (lateral center-edge angle, anterior center-edge angle, acetabular inclination,
      center-to-trochanter distance) and clinical outcomes were measured with the
      modified Harris hip score (mHHS) as well as by prospectively recorded data on
      patient complications and followup. RESULTS: Acetabular labrochondral
      abnormalities included labral hypertrophy in all hips and labral and/or articular
      cartilage lesions requiring treatment in 13 hips. Radiographic analysis
      demonstrated consistent radiographic correction. The median preoperative mHHS
      improved from 64 to 92 at a median followup of 40 months (p < 0.001). Fourteen
      patients (14 hips) had a good or excellent clinical result. Two patients (two
      hips) were classified as failures based on mHHS less than 70 (n = 1) or
      conversion to total hip arthroplasty (n = 1). CONCLUSIONS: Combined surgical hip
      dislocation and PAO provides major deformity correction in Perthes-like hip
      deformities with associated acetabular dysplasia. Early clinical results suggest
      this technique is safe and effective. Long-term studies are needed to determine
      if improved long-term outcomes are associated with comprehensive deformity
      correction.

PMID- 25560961
TI  - CORR Insights((r)): Increased Risk of Periprosthetic Femur Fractures Associated
      With a Unique Cementless Stem Design.

PMID- 25560962
TI  - Cochrane in CORR (r): Intramedullary nails for extracapsular hip fractures in
      adults (review).

PMID- 25560963
TI  - Clinical Faceoff: Trapeziectomy Versus Trapezium Preservation in the Management
      of Basilar Thumb Arthritis.

PMID- 25560964
TI  - CORR Insights((r)): Addition of Vancomycin to Cefazolin Prophylaxis Is Associated
      with Acute Kidney Injury After Primary Joint Arthroplasty.

PMID- 25560965
TI  - Break junction under electrochemical gating: testbed for single-molecule
      electronics.
AB  - Molecular electronics aims to construct functional molecular devices at the
      single-molecule scale. One of the major challenges is to construct a single
      molecule junction and to further manipulate the charge transport through the
      molecular junction. Break junction techniques, including STM break junctions and
      mechanically controllable break junctions are considered as testbed to
      investigate and control the charge transport on a single-molecule scale.
      Moreover, additional electrochemical gating provides a unique opportunity to
      manipulate the energy alignment and molecular redox processes for a single
      molecule junction. In this review, we start from the technical aspects of the
      break junction technique, then discuss the molecular structure-conductance
      correlation derived from break junction studies, and, finally, emphasize
      electrochemical gating as a promising method for the functional molecular
      devices. 

PMID- 25560966
TI  - Transanal total mesorectal excision: full steam ahead.

PMID- 25560967
TI  - Predictive factors for inadequate colon preparation before colonoscopy.
AB  - BACKGROUND: It could be helpful to ascertain which patients are at risk of poor
      bowel preparation prior to performing sedated colonoscopy. The aim of the present
      study was to identify the predictive factors for poor colon preparation prior to
      colonoscopy. METHODS: A prospective study was performed at Kaohsiung Chang Gung
      Memorial Hospital, Taiwan, from September 2011 to May 2013. Patient
      characteristics, food consumed within 2 days of colonoscopy, volume of
      polyethylene glycol (PEG) solution, interval between completing PEG and
      examination, number of bowel movements, and character of the last stool were
      evaluated. RESULTS: Seven hundred and three patients were enrolled (mean age 50.3
      +/- 11.6 years, 43 % female). In univariate analysis, character of the last stool
      (<0.001), body weight (p = 0.007), body mass index (p = 0.047), waist
      circumference (p = 0.008), buttock girth (p = 0.016), meal residue score
      (<0.001), and interval between end of PEG and colonoscopy (p = 0.01) were related
      to inadequate colon preparation. In multivariate analysis, waist circumference (p
      < 0.001), meal residue score (p < 0.001), and characteristics of last stool (p <
      0.001) were variables that predicted poor colon preparation. CONCLUSIONS:
      Patients who have consumed a high residue diet and/or who report that their last
      stool is semisolid are likely to have poor bowel preparation, and consideration
      could be given to rescheduling the examination.

PMID- 25560968
TI  - Factors influencing how senior nurses and midwives acquire and integrate coaching
      skills into routine practice: a grounded theory study.
AB  - AIM: To introduce a theory which describes the process of and explicates the
      factors moderating, the acquisition and integration of leadership coaching skills
      into the routine practice of senior nurses and midwives. BACKGROUND:
      Organizations invest significant resources in leadership coaching programs to
      ensure that coaching is embedded as a core function of the manager's role.
      However, even after training, many managers remain unable to undertake this role
      successfully. The process by which health professionals translate 'manager as
      coach' training into successful practice outcomes, has remained largely
      unexplored. DESIGN: A grounded theory study design. METHODS: Data, collected
      between February 2012-May 2013, included in-depth interviews with 20 senior
      nurses and midwives who had attended a leadership coaching program and analysis
      of nine reflective practice journals. Multiple researchers coded and analysed the
      data using constant comparative techniques. RESULTS: The outcomes of coaching
      training ranged from inappropriate use of the coaching skills through to
      transformed managerial practice. These outcomes were influenced by the dynamic
      interaction of three central domains of the emergent theoretical model: pre
      existing individual perceptions, program elements and contemporaneous
      experiences. Interactions occurred within the domains and between them, impacting
      on activators such as courage, motivation, commitment and confidence. CONCLUSION:
      The study offers new insights into how senior nurses and midwives acquire and
      integrate coaching skills into their routine practice. The process is described
      as multifactorial and dynamic and has implications for the training design,
      delivery and organizational support of future leadership coaching programs.

PMID- 25560969
TI  - Super-duper resolution imaging of mitotic microtubules.

PMID- 25560972
TI  - An outbreak of influenza A (H1N1) virus in a remote Aboriginal community post
      pandemic: implications for pandemic planning and health service policy.
AB  - OBJECTIVE: To describe a 2013 outbreak of pandemic influenza A (H1N1) virus in a
      remote Western Australian Aboriginal community; inform outbreak prevention and
      control measures and discuss the community susceptibility to H1N1, three years
      after the A(H1N1)pdm09 pandemic. METHODS: Records at the local clinic were used
      to classify cases as 'confirmed' (laboratory test positive for H1N1 or
      temperature >38 degrees C with cough and/or sore throat) or 'probable' (self
      reported fever with cough and/or sore throat). Additional data were collected
      from medical records and public health databases. RESULTS: A total of 108
      individuals met case definitions. Clinical attack rate was 23%. Children under
      five years of age had the highest age-specific attack rate (545 per 1,000
      population). Thirty cases (28%) experienced complications with six (5.6%)
      requiring aero-evacuation. Only 7% of the community had received H1N1-containing
      vaccine during the previous year. No H1N1 cases from the community were
      previously reported. CONCLUSIONS: This is the first description of the effects of
      a novel influenza strain on a remote Australian Aboriginal community. Isolation
      and low vaccination are likely explanations for the apparent naivety to H1N1.
      IMPLICATIONS: There may be other remote communities at risk of H1N1. High attack
      and complication rates confirm that Aboriginal Australians should be prioritised
      in pandemic planning.

PMID- 25560973
TI  - The combined effect of cancer and chronic diseases on general practitioner
      consultation rates.
AB  - AIM: More than two-thirds of cancer patients have one or more chronic diseases
      besides cancer. The purpose of this study was to get detailed insight into the
      combined effect of cancer and chronic diseases on general practitioner (GP)
      consultation rates. METHODS: From the NIVEL Primary Care Database we identified
      cancer patients with diabetes mellitus (n=629), osteoarthritis (n=425), coronary
      artery disease (n=466), COPD (n=383) or without a chronic disease (n=1507),
      diagnosed with cancer between 2002 and 2010. They were matched on sex, age,
      practice and chronic disease to 6645 non-cancer controls. RESULTS: 2-5 years
      after diagnosis, cancer patients without a chronic disease had on average 6.5 GP
      contacts per year, those with a comorbid disease almost twice as many (ranging
      from 10 for osteoarthritis to 12.4 for COPD). A similar difference was seen in
      non-cancer controls. The number of GP contacts for chronic diseases did not
      differ between cancer patients and controls. The increase in the number of GP
      consultations with age and number of chronic diseases was similar in cancer
      patients and controls. Consultation rates were similar in cancer patients and
      controls if they were stratified by number of chronic diseases while counting
      cancer as a chronic disease. CONCLUSIONS: Two to five years after diagnosis,
      cancer leads to an increase in GP contacts that is similar to having a chronic
      disease. This increase does not differ between those with and without a chronic
      disease and cancer does not seem to increase the impact of having a chronic
      disease.

PMID- 25560970
TI  - Mechanisms of retinoic acid signalling and its roles in organ and limb
      development.
AB  - Retinoic acid (RA) signalling has a central role during vertebrate development.
      RA synthesized in specific locations regulates transcription by interacting with
      nuclear RA receptors (RARs) bound to RA response elements (RAREs) near target
      genes. RA was first implicated in signalling on the basis of its teratogenic
      effects on limb development. Genetic studies later revealed that endogenous RA
      promotes forelimb initiation by repressing fibroblast growth factor 8 (Fgf8).
      Insights into RA function in the limb serve as a paradigm for understanding how
      RA regulates other developmental processes. In vivo studies have identified RAREs
      that control repression of Fgf8 during body axis extension or activation of
      homeobox (Hox) genes and other key regulators during neuronal differentiation and
      organogenesis. 

PMID- 25560971
TI  - Quantitative system drift compensates for altered maternal inputs to the gap gene
      network of the scuttle fly Megaselia abdita.
AB  - The segmentation gene network in insects can produce equivalent phenotypic
      outputs despite differences in upstream regulatory inputs between species. We
      investigate the mechanistic basis of this phenomenon through a systems-level
      analysis of the gap gene network in the scuttle fly Megaselia abdita (Phoridae).
      It combines quantification of gene expression at high spatio-temporal resolution
      with systematic knock-downs by RNA interference (RNAi). Initiation and dynamics
      of gap gene expression differ markedly between M. abdita and Drosophila
      melanogaster, while the output of the system converges to equivalent patterns at
      the end of the blastoderm stage. Although the qualitative structure of the gap
      gene network is conserved, there are differences in the strength of regulatory
      interactions between species. We term such network rewiring 'quantitative system
      drift'. It provides a mechanistic explanation for the developmental hourglass
      model in the dipteran lineage. Quantitative system drift is likely to be a
      widespread mechanism for developmental evolution. 

PMID- 25560974
TI  - Racial differences in three major NHL subtypes: descriptive epidemiology.
AB  - BACKGROUND: NHL (non-Hodgkin lymphoma) consists of over 60 subtypes, ranging from
      slow-growing to very aggressive. The three largest subtypes are DLBCL (diffuse
      large B-cell lymphoma), FL (follicular lymphoma), and CLL/SLL (chronic
      lymphocytic leukemia/small lymphocytic lymphoma). For each subtype, different
      racial groups have different presentations, etiologies, and prognosis patterns.
      METHODS: SEER (Surveillance, Epidemiology, and End Results) data on DLBCL, FL,
      and CLL/SLL patients diagnosed between 1992 and 2010 were analyzed. Racial groups
      studied included NHW (non-Hispanic whites), HW (Hispanic whites), blacks, and API
      (Asians and Pacific Islanders). Patient characteristics, age-adjusted incidence
      rate, and survival were compared across races. Stratification and multivariate
      analysis were conducted. RESULTS: There are significant racial differences for
      patients' characteristics, including gender, age at diagnosis, stage, lymph site,
      and age, and the patterns vary across subtypes. NHWs have the highest incidence
      rates for all three subtypes, followed by HWs (DLBCL and FL) and blacks
      (CLL/SLL). The dependence of the incidence rate on age and gender varies across
      subtypes. For all three subtypes, NHWs have the highest five-year relative
      survival rates, followed by HWs. When stratified by stage, racial difference is
      significant in multiple multivariate Cox regression analyses. CONCLUSIONS: Racial
      differences exist among DLBCL, FL, and CLL/SLL patients in the U.S. in terms of
      characteristics, incidence, and survival. The patterns vary across subtypes. More
      data collection and analysis are needed to more comprehensively describe and
      interpret the across-race and subtype differences.

PMID- 25560975
TI  - Primary prevention: do the very elderly require a different approach?
AB  - Recent cardiovascular prevention guidelines place a greater emphasis on
      randomized placebo-controlled trial data as the basis for recommendations. While
      such trial data are sparse for people over the age of 75 or 80 years, data
      demonstrate altered risk-benefit relationships in these older patients. Primary
      prevention strategy decisions should consider estimated life expectancy and
      overall function as well as cardiovascular event risks, magnitude and time to
      benefit or harm, potentially altered adverse effect profiles, and informed
      patient preferences. Data support treatment of systolic hypertension to reduce
      stroke, cardiovascular events, and dementia in older patients with at least a 2
      year estimated lifespan with modifications in systolic blood pressure goals and a
      need for greater attention to non-cardiovascular side effects such as falls in
      the very old. Lowering of elevated cholesterol levels with HMG-CoA reductase
      inhibitors for primary prevention in people over the age of 75 years requires
      greater individual considerations, as benefits may not accrue for 3-5 years and
      there is the potential impact of adverse effects. There is a rationale for lipid
      lowering treatment in the more highly functional older patient with
      cardiovascular (especially stroke) risk higher than side effect risks in the near
      term and with an estimated lifespan longer than the time to benefit. Aspirin has
      higher side effect risks and requires a longer time to achieve benefit. Trial
      data are lacking on exercise interventions, but multi-system benefits have been
      shown in older patients such that exercise should be part of a preventive
      regimen. Preventive therapy in the very old means considering not only medical
      issues of co-morbidities, polypharmacy, and altered risk-benefit relationship of
      medications but also adjusting goals and approaches across the older agespan in
      keeping with informed patient preferences. 

PMID- 25560976
TI  - DC3-decorated polyplexes for targeted gene delivery into dendritic cells.
AB  - Dendritic cells (DCs) are a family of specialized antigen presenting cells (APCs)
      that detect antigens and initiate a wide spectrum of immune responses against
      them. These characteristics make them promising candidates for immunotherapy
      manipulations. In this study we designed and synthesized DC-targeted block
      copolymers composed of linear polyethylenimine (PEI) conjugated to hydrophilic
      polyethylene glycol (PEG) installed with a DC-targeting peptide (DC3, primary
      sequence FYPSYHSTPQRP). Two different conjugation procedures (basic and modified)
      were employed to synthesize the DC3-PEG-b-PEI and the control SCRM-PEG-b-PEI
      (with a scrambled DC3 peptide sequence) by one-pot synthesis, in two steps. In
      the first, basic conjugation procedure, PEG with N-hydroxysuccinimide (NHS) ester
      and maleimide (MAL) groups (NHS-PEG-MAL, 3.5 kDa) was first coupled to linear PEI
      (25 kDa) via the NHS group to yield the intermediate MAL-PEG-b-PEI, that was then
      conjugated to N-terminus-cysteine harboring peptides DC3 or SCRM via the MAL
      double bond to yield the final DC3-PEG-b-PEI or SCRM-PEG-b-PEI copolymers,
      respectively. In the second, modified conjugation procedure, Fmoc-cysteine
      harboring DC3 or SCRM peptides were first conjugated to NHS-PEG-MAL via the MAL
      group followed by coupling to linear PEI via the NHS functional group. Fmoc
      cleavage yielded the same final product as in the basic procedure. The modified
      conjugation procedure was capable of yielding block copolymers richer with
      peptides, as determined by (1)H NMR analysis. Self-assembly of DC3-PEG-b-PEI
      copolymers and DNA molecules yielded nanosized polyion complexes (polyplexes),
      with lower surface charge and limited cytotoxicity when compared to the PEI
      building block. Significant transfection efficiency of the DC-targeted polyplexes
      by murine dendritic DC2.4 cells was observed only in DC3-PEG-b-PEI/DNA polyplexes
      synthesized by the modified conjugation procedure. These polyplexes, with higher
      peptide-load, showed greater transfection capability in DC2.4 cells relative to
      the control nontargeted SCRM-PEG-b-PEI/DNA polyplexes, but not in endothelial
      cells. The transfection efficiency was comparable to or higher than that of the
      PEI/DNA positive control. The results indicate that PEGylated-PEI polyplexes show
      significant transfection efficiency into DCs when decorated with DC3 peptide, and
      are attractive candidates for immunotherapy via DCs. 

PMID- 25560977
TI  - Case management approaches to home support for people with dementia.
AB  - BACKGROUND: Over 35 million people are estimated to be living with dementia in
      the world and the societal costs are very high. Case management is a widely used
      and strongly promoted complex intervention for organising and co-ordinating care
      at the level of the individual, with the aim of providing long-term care for
      people with dementia in the community as an alternative to early admission to a
      care home or hospital. OBJECTIVES: To evaluate the effectiveness of case
      management approaches to home support for people with dementia, from the
      perspective of the different people involved (patients, carers, and staff)
      compared with other forms of treatment, including 'treatment as usual', standard
      community treatment and other non-case management interventions. SEARCH METHODS:
      We searched the following databases up to 31 December 2013: ALOIS, the
      Specialised Register of the Cochrane Dementia and Cognitive Improvement Group,The
      Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, Web of Science
      (including Science Citation Index Expanded (SCI-EXPANDED) and Social Science
      Citation Index), Campbell Collaboration/SORO database and the Specialised
      Register of the Cochrane Effective Practice and Organisation of Care Group. We
      updated this search in March 2014 but results have not yet been incorporated.
      SELECTION CRITERIA: We include randomised controlled trials (RCTs) of case
      management interventions for people with dementia living in the community and
      their carers. We screened interventions to ensure that they focused on planning
      and co-ordination of care. DATA COLLECTION AND ANALYSIS: We used standard
      methodological procedures as required by The Cochrane Collaboration. Two review
      authors independently extracted data and made 'Risk of bias' assessments using
      Cochrane criteria. For continuous outcomes, we used the mean difference (MD) or
      standardised mean difference (SMD) between groups along with its confidence
      interval (95% CI). We applied a fixed- or random-effects model as appropriate.
      For binary or dichotomous data, we generated the corresponding odds ratio (OR)
      with 95% CI. We assessed heterogeneity by the I2 statistic. MAIN RESULTS: We
      include 13 RCTs involving 9615 participants with dementia in the review. Case
      management interventions in studies varied. We found low to moderate overall risk
      of bias; 69% of studies were at high risk for performance bias.The case
      management group were significantly less likely to be institutionalised
      (admissions to residential or nursing homes) at six months (OR 0.82, 95% CI 0.69
      to 0.98, n = 5741, 6 RCTs, I2 = 0%, P = 0.02) and at 18 months (OR 0.25, 95% CI
      0.10 to 0.61, n = 363, 4 RCTs, I2 = 0%, P = 0.003). However, the effects at 10 -
      12 months (OR 0.95, 95% CI 0.83 to 1.08, n = 5990, 9 RCTs, I2 = 48%, P = 0.39)
      and 24 months (OR 1.03, 95% CI 0.52 to 2.03, n = 201, 2 RCTs, I2 = 0%, P = 0.94)
      were uncertain. There was evidence from one trial of a reduction in the number of
      days per month in a residential home or hospital unit in the case management
      group at six months (MD -5.80, 95% CI -7.93 to -3.67, n = 88, 1 RCT, P < 0.0001)
      and at 12 months (MD -7.70, 95% CI -9.38 to -6.02, n = 88, 1 RCT, P < 0.0001).
      One trial reported the length of time until participants were institutionalised
      at 12 months and the effects were uncertain (hazard ratio (HR): 0.66, 95% CI 0.38
      to 1.14, P = 0.14). There was no difference in the number of people admitted to
      hospital at six (4 RCTs, 439 participants), 12 (5 RCTs, 585 participants) and 18
      months (5 RCTs, 613 participants). For mortality at 4 - 6, 12, 18 - 24 and 36
      months, and for participants' or carers' quality of life at 4, 6, 12 and 18
      months, there were no significant effects. There was some evidence of benefits in
      carer burden at six months (SMD -0.07, 95% CI -0.12 to -0.01, n = 4601, 4 RCTs,
      I2 = 26%, P = 0.03) but the effects at 12 or 18 months were uncertain.
      Additionally, some evidence indicated case management was more effective at
      reducing behaviour disturbance at 18 months (SMD -0.35, 95% CI -0.63 to -0.07, n
      = 206, 2 RCTs I2 = 0%, P = 0.01) but effects were uncertain at four (2 RCTs), six
      (4 RCTs) or 12 months (5 RCTs).The case management group showed a small
      significant improvement in carer depression at 18 months (SMD -0.08, 95% CI -0.16
      to -0.01, n = 2888, 3 RCTs, I2 = 0%, P = 0.03). Conversely, the case management
      group showed greater improvement in carer well-being in a single study at six
      months (MD -2.20 CI CI -4.14 to -0.26, n = 65, 1 RCT, P = 0.03) but the effects
      were uncertain at 12 or 18 months. There was some evidence that case management
      reduced the total cost of services at 12 months (SMD -0.07, 95% CI -0.12 to 
      0.02, n = 5276, 2 RCTs, P = 0.01) and incurred lower dollar expenditure for the
      total three years (MD= -705.00, 95% CI -1170.31 to -239.69, n = 5170, 1 RCT, P =
      0.003). Data on a number of outcomes consistently indicated that the intervention
      group received significantly more community services. AUTHORS' CONCLUSIONS: There
      is some evidence that case management is beneficial at improving some outcomes at
      certain time points, both in the person with dementia and in their carer.
      However, there was considerable heterogeneity between the interventions, outcomes
      measured and time points across the 13 included RCTs. There was some evidence
      from good-quality studies to suggest that admissions to care homes and overall
      healthcare costs are reduced in the medium term; however, the results at longer
      points of follow-up were uncertain. There was not enough evidence to clearly
      assess whether case management could delay institutionalisation in care homes.
      There were uncertain results in patient depression, functional abilities and
      cognition. Further work should be undertaken to investigate what components of
      case management are associated with improvement in outcomes. Increased
      consistency in measures of outcome would support future meta-analysis.

PMID- 25560978
TI  - Regulatory review time for approval of oncology drugs in Japan between 2001 and
      2014. Considerations of changes, factors that affect review time, and difference
      with the United States.
AB  - In this study, we comprehensively and historically studied the review time of
      oncology drugs approved by the regulatory authorities in Japan with publicly
      available information. A total of 120 applications of oncology drugs were
      approved in Japan between April 2001 and July 2014. The review time peaked with
      732.0 days (24.4 months) in 2005, and showed a tendency to decline gradually each
      year thereafter. After 2012, a significant reduction of the review time was seen
      in comparison to the median of 13-year median time. In addition, we compared the
      review time with that in the United States. The median review time lag with the
      United States was significantly peaked in 2005. After 2005, the review time lag
      with the FDA has decreased, but lag did not significantly reduce by 2014. We also
      examined factors influencing the review time in Japan with multiple regression
      analysis. It was found that the factors related to a use of overseas data and
      expedited program for accelerating the reviews influenced the direction of
      shortening the review time. We consider that regulatory authorities in Japan need
      to keep making efforts to reduce the review time further and eliminate the review
      time lag with the United States. 

PMID- 25560979
TI  - Coagulation-agglomeration of fractal-like particles: structure and self
      preserving size distribution.
AB  - Agglomeration occurs in environmental and industrial processes, especially at low
      temperatures where particle sintering or coalescence is rather slow. Here, the
      growth and structure of particles undergoing agglomeration (coagulation in the
      absence of coalescence, condensation, or surface growth) are investigated from
      the free molecular to the continuum regime by discrete element modeling (DEM).
      Particles coagulating in the free molecular regime follow ballistic trajectories
      described by an event-driven method, whereas in the near-continuum (gas-slip) and
      continuum regimes, Langevin dynamics describe their diffusive motion.
      Agglomerates containing about 10-30 primary particles, on the average, attain
      their asymptotic fractal dimension, D(f), of 1.91 or 1.78 by ballistic or
      diffusion-limited cluster-cluster agglomeration, corresponding to coagulation in
      the free molecular or continuum regimes, respectively. A correlation is proposed
      for the asymptotic evolution of agglomerate D(f) as a function of the average
      number of constituent primary particles, n(p). Agglomerates exhibit considerably
      broader self-preserving size distribution (SPSD) by coagulation than spherical
      particles: the number-based geometric standard deviations of the SPSD agglomerate
      radius of gyration in the free molecular and continuum regimes are 2.27 and 1.95,
      respectively, compared to ~1.45 for spheres. In the transition regime,
      agglomerates exhibit a quasi-SPSD whose geometric standard deviation passes
      through a minimum at Knudsen number Kn ~ 0.2. In contrast, the asymptotic D(f)
      shifts linearly from 1.91 in the free molecular regime to 1.78 in the continuum
      regime. Population balance models using the radius of gyration as collision
      radius underestimate (up to about 80%) the small tail of the SPSD and slightly
      overpredict the overall agglomerate coagulation rate, as they do not account for
      cluster interpenetration during coagulation. In the continuum regime, when a
      recently developed agglomeration rate is used in population balance equations,
      the resulting SPSD is in excellent agreement with that obtained by DEM.

PMID- 25560981
TI  - Divergent selection for shape of the growth curve in Japanese quail. 8. Effect of
      long-term selection on embryonic development and growth.
AB  - 1. Changes in embryonic development and growth were analysed in relation to
      direct changes in postnatal growth and correlated responses in egg parameters
      using Japanese quail lines selected for more than 30 generations for high (HG)
      and low (LG) relative gain of body weight (BW) between 11 and 28 d of age, and
      constant BW at 49 d of age. 2. During the first 42 h as well as at the end of
      incubation, LG embryos were developmentally accelerated in comparison with their
      HG counterparts. An expected increase of line divergence across generations was
      observed only in traits analysed at the end of incubation. 3. In contrast to
      early generations, LG embryos continuously exhibited a higher BW than HG embryos
      and this difference temporarily disappeared only around incubation d 8. Analogous
      to early generations, the HG compared with LG embryos showed two periods of
      transient growth retardation compensated subsequently by a higher growth rate
      (incubation d 3-8 and 8-16). 4. More pronounced growth retardation of HG versus
      LG embryos in late versus early generations corresponded to more distinct
      decrease of HG versus LG growth rate during the first post-hatch days. Likewise,
      a disappearance of line BW differences on incubation d 8 characterising the late
      generations corresponded to the elimination of line differences in adult BW. 5.
      Alterations of growth pattern were associated with changes of egg size. While HG
      quail maintained a relatively constant adult BW and egg size across generations,
      the gradually increasing incidence of large eggs in the LG line allowed selection
      of birds with higher growth potential, which in turn amplified the line
      differences in the embryonic BW and eliminated the line differences in adult BW.
      Line differences in egg composition (larger albumen with lower density in LG
      compared with HG eggs) apparently contributed to the strengthening of line
      developmental divergence during incubation. 6. Transient lack of nutrient supply
      to HG embryos due to their developmental delay is probably responsible for a
      higher HG versus LG embryo mortality. 

PMID- 25560980
TI  - Fungi in the future: interannual variation and effects of atmospheric change on
      arbuscular mycorrhizal fungal communities.
AB  - Understanding the natural dynamics of arbuscular mycorrhizal (AM) fungi and their
      response to global environmental change is essential for the prediction of future
      plant growth and ecosystem functions. We investigated the long-term temporal
      dynamics and effect of elevated atmospheric carbon dioxide (CO2 ) and ozone (O3 )
      concentrations on AM fungal communities. Molecular methods were used to
      characterize the AM fungal communities of soybean (Glycine max) grown under
      elevated and ambient atmospheric concentrations of both CO2 and O3 within a free
      air concentration enrichment experiment in three growing seasons over 5 yr.
      Elevated CO2 altered the community composition of AM fungi, increasing the ratio
      of Glomeraceae to Gigasporaceae. By contrast, no effect of elevated O3 on AM
      fungal communities was detected. However, the greatest compositional differences
      detected were between years, suggesting that, at least in the short term, large
      scale interannual temporal dynamics are stronger mediators than atmospheric CO2
      concentrations of AM fungal communities. We conclude that, although atmospheric
      change may significantly alter AM fungal communities, this effect may be masked
      by the influences of natural changes and successional patterns through time. We
      suggest that changes in carbon availability are important determinants of the
      community dynamics of AM fungi.

PMID- 25560982
TI  - Dapagliflozin: drug profile and its role in individualized treatment.
AB  - Dapagliflozin is the first sodium-glucose co-transporter inhibitor developed. An
      extensive program covering all phases of clinical research showed us the efficacy
      and safety profile of the drug. Dapagliflozin and the other SGLT2 inhibitors are
      a new treatment alternative in patients with Type 2 diabetes either as
      monotherapy or combined with the hypoglycemic agents currently available and is
      approved in approximately 38 countries worldwide. This drug profile provides the
      necessary tools to assess the risks and benefits of this new molecule. 

PMID- 25560984
TI  - Search for blood or water is influenced by Borrelia burgdorferi in Ixodes
      ricinus.
AB  - An increasing number of studies suggest that vector-borne parasites are able to
      alter phenotypic traits in their arthropod vectors so that microorganism
      transmission is enhanced. This review documents this phenomenon, which occurs
      between Borrelia burgdorferi bacteria, the causative agents of Lyme borreliosis,
      and their tick vectors belonging to the Ixodes ricinus complex. It also reviews
      the influence of other tick-borne pathogens on these ticks. Ticks belonging to
      the Ixodes ricinus complex benefit from Borrelia infection by an increased
      lifespan (more fat and more resistance to desiccation) and by an increased
      questing period (less need to move to the litter zone to rehydrate), which
      enhances tick chances to find a host and to subsequently transmit the pathogens. 

PMID- 25560986
TI  - Selective removal of alkali metal cations from multiply-charged ions via gas
      phase ion/ion reactions using weakly coordinating anions.
AB  - Selective removal of alkali metal cations from mixed cation multiply-charged
      peptide ions is demonstrated here using gas-phase ion/ion reactions with a series
      of weakly coordinating anions (WCAs), including hexafluorophosphate (PF6 (-)),
      tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BARF),
      tetrakis(pentafluorophenyl)borate (TPPB), and carborane (CHB11Cl11 (-)). In all
      cases, a long-lived complex is generated by dication/anion condensation followed
      by ion activation to compare proton transfer with alkali ion transfer from the
      peptide to the anion. The carborane anion was the only anion studied to undergo
      dissociation exclusively through loss of the metallated anion, regardless of the
      studied metal adduct. All other anions studied yield varying abundances of
      protonated and metallated peptide depending on the peptide sequence and the metal
      identity. Density functional theory calculations suggest that for the WCAs
      studied, metal ion transfer is most strongly favored thermodynamically, which is
      consistent with the experimental results. The carborane anion is demonstrated to
      be a robust reagent for the selective removal of alkali metal cations from
      peptide cations with mixtures of excess protons and metal cations. 

PMID- 25560985
TI  - Single nucleotide polymorphisms of Toll-like receptors and susceptibility to
      infectious diseases.
AB  - Toll-like receptors (TLRs) are the best-studied family of pattern-recognition
      receptors (PRRs), whose task is to rapidly recognize evolutionarily conserved
      structures on the invading microorganisms. Through binding to these patterns,
      TLRs trigger a number of proinflammatory and anti-microbial responses, playing a
      key role in the first line of defence against the pathogens also promoting
      adaptive immunity responses. Growing amounts of data suggest that single
      nucleotide polymorphisms (SNPs) on the various human TLR proteins are associated
      with altered susceptibility to infection. This review summarizes the role of TLRs
      in innate immunity, their ligands and signalling and focuses on the TLR SNPs
      which have been linked to infectious disease susceptibility. 

PMID- 25560988
TI  - Detection of posaconazole by surface-assisted laser desorption/ionization mass
      spectrometry with dispersive liquid-liquid microextraction.
AB  - A simple, rapid, and sensitive method for the detection of posaconazole using
      dispersive liquid-liquid microextraction (DLLME) coupled to surface-assisted
      laser desorption/ionization mass spectrometric detection (SALDI/MS) was
      developed. After the DLLME, posaconazole was detected using SALDI/MS with
      colloidal gold and alpha-cyano-4-hydroxycinnamic acid (CHCA) as the co-matrix.
      Under optimal extraction and detection conditions, the calibration curve, which
      ranged from 1.0 to 100.0 nM for posaconazole, was observed to be linear. The
      limit of detection (LOD) at a signal-to-noise ratio of 3 was 0.3 nM for
      posaconazole. This novel method was successfully applied to the determination of
      posaconazole in human urine samples. 

PMID- 25560989
TI  - High-alert medications in a French paediatric university hospital.
AB  - RATIONALE, AIMS AND OBJECTIVES: High-alert medications (HAMs) are medications
      that are associated with a high risk of serious harm if used improperly. The
      objective of this study was to identify paediatric HAM used in our institution
      and to identify safety measures for their use. METHODS: The list of HAM and the
      list of safety measures that were introduced in our department were based on (1)
      a literature search; (2) a survey of health care professionals in our department
      including doctors, head nurses, nurses and pharmacists; and (3) the drug steering
      committee. RESULTS: We found four lists of HAM based on a literature search,
      including 27 classes of pharmaceutical agents, and 63 common drug names. The
      response rate of the survey was 20.7% (230 of 1113). Some of the HAMs included in
      our list were not identified by the literature search. These included neuroleptic
      drugs, anti-malarial agents, antiviral agents, anti-retroviral agents and
      intravenous acetaminophen. The drug steering committee selected 17 HAM and
      highlighted 53 safety measures involving seven broad aspects of pharmacological
      management. CONCLUSIONS: This project was part of the new safety strategies
      developed in a paediatric hospital. We set out to make a list of HAM relevant to
      paediatrics with additional safety measures to prevent medication errors
      associated and a 'joker' system. The various safety measures, such as double
      checking of HAM prescriptions, should be reviewed during the year following their
      implementation. This list, which was developed in our hospital specifically for
      use in paediatrics, can be adapted for use in other paediatric departments.

PMID- 25560987
TI  - "De-novo" amino acid sequence elucidation of protein G'e by combined "top-down"
      and "bottom-up" mass spectrometry.
AB  - Mass spectrometric de-novo sequencing was applied to review the amino acid
      sequence of a commercially available recombinant protein G' with great scientific
      and economic importance. Substantial deviations to the published amino acid
      sequence (Uniprot Q54181) were found by the presence of 46 additional amino acids
      at the N-terminus, including a so-called "His-tag" as well as an N-terminal
      partial alpha-N-gluconoylation and alpha-N-phosphogluconoylation, respectively.
      The unexpected amino acid sequence of the commercial protein G' comprised 241
      amino acids and resulted in a molecular mass of 25,998.9 +/- 0.2 Da for the
      unmodified protein. Due to the higher mass that is caused by its extended amino
      acid sequence compared with the original protein G' (185 amino acids), we named
      this protein "protein G'e." By means of mass spectrometric peptide mapping, the
      suggested amino acid sequence, as well as the N-terminal partial alpha-N
      gluconoylations, was confirmed with 100% sequence coverage. After the protein G'e
      sequence was determined, we were able to determine the expression vector pET-28b
      from Novagen with the Xho I restriction enzyme cleavage site as the best option
      that was used for cloning and expressing the recombinant protein G'e in E. coli.
      A dissociation constant (K(d)) value of 9.4 nM for protein G'e was determined
      thermophoretically, showing that the N-terminal flanking sequence extension did
      not cause significant changes in the binding affinity to immunoglobulins.

PMID- 25560990
TI  - Integrated Ugi-based assembly of functionally, skeletally, and stereochemically
      diverse 1,4-benzodiazepin-2-ones.
AB  - A practical, integrated and versatile U-4CR-based assembly of 1,4-benzodiazepin-2
      ones exhibiting functionally, skeletally, and stereochemically diverse
      substitution patterns is described. By virtue of its convergence, atom economy,
      and bond-forming efficiency, the methodology documented herein exemplifies the
      reconciliation of structural complexity and experimental simplicity in the
      context of medicinal chemistry projects. 

PMID- 25560991
TI  - Modulation of PPARgamma and TNFalpha by emu oil and glycyrrhizin in ulcerative
      colitis.
AB  - Ulcerative Colitis (UC) is an inflammatory bowel disorder that affects colon and
      rectum. Treatments in many UC patients remain variably effective and are
      associated with considerable adverse effects. So the present study was undertaken
      to explore the antiinflammatory effects of emu oil, glycyrrhizin, and combination
      of emu oil and glycyrrhizin in acetic acid-induced UC in rats. UC was induced by
      intracolonic instillation of 5% acetic acid in rats. Emu oil and glycyrrhizin
      were orally administered to test groups. Severity of colitis was scored
      macroscopically and microscopically. The levels of myeloperoxidase and
      antioxidant enzymes namely catalase, superoxide dismutase and glutathione
      peroxidase were assessed spectrophotometrically. Expressions of PPARgamma and
      TNFalpha were studied by real-time PCR. Acetic acid caused severe damage to colon
      and rectum. Emu oil and glycyrrhizin were found to significantly reduce
      macroscopic and microscopic lesions and decrease levels of myeloperoxidase. There
      was a significant improvement of antioxidant levels in treatment groups compared
      to acetic acid group. Combination of emu oil and glycyrrhizin showed a markedly
      greater modulation of PPARgamma and TNFalpha expression than emu oil and
      glycyrrhizin when administered alone. Combination of emu oil and glycyrrhizin
      might have had synergistic effects in regulating PPARgamma and TNFalpha. Further
      studies on mechanism of action of emu oil and glycyrrhizin combination would pave
      the way to define possibility of this combination as effective in the management
      of UC.

PMID- 25560993
TI  - Analysis and evaluation of tasty components in the pileus and stipe of Lentinula
      edodes at different growth stages.
AB  - Tasty components in Lentinula edodes pileus and stipe at different growth stages
      were studied. Mannitol, trehalose, arabitol, and glucose were the main soluble
      polyols and sugars, whereas succinic acid, malic acid, and citric acid were the
      main organic acids. Mannitol contents were the highest in the pileus and
      increased at mature growth stages, although arabitol contents were the highest in
      the stipe and peaked at stage 5. Succinic acid contents peaked at stage 5 in the
      pileus and stipe during mature growth stages. Threonine (sweet taste) values were
      the highest among all the detected amino acids, followed by glutamic acid (MSG
      like taste). MSG-like 5'-nucleotide contents could account for nearly 50% of the
      total 5'-nucleotides. Equivalent umami concentration (EUC) values of stage 5
      exhibited higher levels during mature growth stages. Tasty components in the
      stipe were rich and EUC values were high, which might be useful for further
      processing and byproduct development of L. edodes. 

PMID- 25560994
TI  - Widening functional boundaries of the sigma(54) promoter Pu of Pseudomonas putida
      by defeating extant physiological constraints.
AB  - The extant layout of the sigma(54) promoter Pu, harboured by the catabolic TOL
      plasmid, pWW0, of Pseudomonas putida is one of the most complex instances of
      endogenous and exogenous signal integration known in the prokaryotic domain. In
      this regulatory system, all signal inputs are eventually translated into
      occupation of the promoter sequence by either of two necessary components: the m
      xylene responsive transcriptional factor XylR and the sigma(54) containing form
      of RNA polymerase. Modelling of these components indicated that the Pu promoter
      could be upgraded to respond with much greater capacity to aromatic inducers by
      artificially increasing the endogenous levels of both XylR and the sigma(54)
      sigma factor, either separately or together. To explore these scenarios,
      expression of rpoN, the gene encoding sigma(54), was placed under the control of
      an orthogonal regulatory system that was inducible by salicylic acid. We
      generated a knock-in P. putida strain containing this construct alongside the
      xylR/Pu regulatory module in its native configuration, and furthermore, a second
      strain where xylR expression was under the control of an engineered positive
      feedback loop. These interventions allowed us to dramatically increase the
      transcriptional capacity (i.e. absolute promoter output) of Pu far beyond its
      natural scope. In addition, they resulted in a new regulatory device displaying
      more sensitive and ultra-fast responses to m-xylene. To our knowledge, this is
      the first time that the working regime of a promoter has been rationally modified
      by releasing the constraints imposed by its innate constituents. 

PMID- 25560992
TI  - Imaging the zebrafish dentition: from traditional approaches to emerging
      technologies.
AB  - The zebrafish, a model organism for which a plethora of molecular and genetic
      techniques exists, has a lifelong replacing dentition of 22 pharyngeal teeth.
      This is in contrast to the mouse, which is the key organism in dental research
      but whose teeth are never replaced. Employing the zebrafish as the main organism
      to elucidate the mechanisms of continuous tooth replacement, however, poses at
      least one major problem, related to the fact that all teeth are located deep
      inside the body. Investigating tooth replacement thus relies on conventional
      histological methods, which are often laborious, time-consuming and can cause
      tissue deformations. In this review, we investigate the advantages and
      limitations of adapting current visualization techniques to dental research in
      zebrafish. We discuss techniques for fast sectioning, such as vibratome
      sectioning and high-resolution episcopic microscopy, and methods for in toto
      visualization, such as Alizarin red staining, micro-computed tomography, and
      optical projection tomography. Techniques for in vivo imaging, such as two-photon
      excitation fluorescence and second harmonic generation microscopy, are also
      covered. Finally, the possibilities of light sheet microscopy are addressed. 

PMID- 25560996
TI  - Radiological assessment of irreducible posterolateral knee subluxation after
      dislocation due to interposition of the vastus medialis: a case report.
AB  - Knee dislocation is a serious and relatively uncommon traumatism that every
      emergency room is supposed to diagnose and treat rapidly. Most of the time these
      dislocations reduce spontaneously or with closed reduction. If a subluxation
      persists, an incarceration of soft tissue in the joint must be suspected.
      Irreducible knee subluxations after dislocation are rare entities better
      described in the orthopaedic than in the radiological literature. However, the
      initial radiological assessment is an important tool to obtain the correct
      diagnosis, to detect neurovascular complications, and to plan the most suitable
      treatment. In cases of delayed diagnosis, the functional prognosis of the joint
      and even the limb may be seriously compromised primarily because of vascular
      lesions. Thereby, vascular imaging is essential in cases of dislocation of the
      knee, and we will discuss the role of angiography and the more recent use of
      computed tomography angiography or magnetic resonance angiography. Our patient
      presented with an irreducible knee subluxation due to interposition of the vastus
      medialis, and we will review the classical clinical presentation and 'do not
      miss' imaging findings on conventional radiography, computed tomography
      angiography, and magnetic resonance imaging. Finally, we will also report the
      classical imaging pathway indicated in knee dislocation, with a special emphasis
      on the irreducible form. 

PMID- 25560997
TI  - Frequency, imaging findings, risk factors, and long-term sequelae of distal
      clavicular osteolysis in young patients.
AB  - OBJECTIVE: Atraumatic distal clavicular osteolysis (DCO) has been described in
      adult male weightlifters. Our purpose was to investigate the frequency, magnetic
      resonance imaging (MRI) characteristics, risk factors, and long-term sequelae of
      DCO in young patients. MATERIALS AND METHODS: Individuals with atraumatic DCO
      were identified in a retrospective review of 1,432 consecutive MRI shoulder
      reports in patients between 13 and 19 years of age. MRI findings of DCO,
      association with athletic activity, short-term clinical outcome after 3-6 months,
      and long-term clinical and MRI outcome after 2 years were analyzed. A pre-MRI
      questionnaire assessed the patients' athletic history including overhead activity
      and weightlifting. RESULTS: At a mean age of 15.9 years, 6.5 % (93/1432) of
      patients had atraumatic DCO, and 24 % were females. The combination of an
      overhead sport (basketball, volleyball, tennis, swimming) and supplemental weight
      training was a risk factor for DCO (odds ratio = 38, p = 0.01). Ninety-three
      percent of patients responded to conservative therapy. On follow-up imaging, 71 %
      of DCO patients had acromioclavicular (AC) joint osteoarthritis (vs. 35 % in
      controls, p = 0.006); 79 % had flattening of the distal clavicle and interval
      widening of the AC joint to a mean of 5.0 mm (compared to 2.4 mm in controls, p <
      0.001). Severity of DCO edema was associated with pain (p < 0.02) at initial
      presentation and with AC joint osteoarthritis (p = 0.004) on follow-up.
      CONCLUSION: In athletic teenagers, the combination of weightlifting and overhead
      activity is a risk factor for atraumatic DCO, and females are affected in 24 %.
      Long-term sequelae include widening of the AC joint and AC joint osteoarthritis.

PMID- 25560998
TI  - Characterization of equine urinary metabolites of selective androgen receptor
      modulators (SARMs) S1, S4 and S22 for doping control purposes.
AB  - Selective androgen receptor modulators, SARMs, constitute a class of compounds
      with anabolic properties but with few androgenic side-effects. This makes them
      possible substances of abuse and the World Anti-Doping Agency (WADA) has banned
      the entire class of substances. There have been several cases of illicit use of
      aryl propionamide SARMs in human sports and in 2013, 13 cases were reported.
      These substances have been found to be extensively metabolized in humans, making
      detection of metabolites necessary for doping control. SARMs are also of great
      interest to equine doping control, but the in vivo metabolite pattern and thus
      possible analytical targets have not been previously studied in this species. In
      this study, the urinary metabolites of the SARMs S1, S4, and S22 in horses were
      studied after intravenous injection, using ultra high performance liquid
      chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QToF
      MS). Eight different metabolites were found for SARM S1, nine for SARM S4, and
      seven for SARM S22. The equine urinary metabolite profiles differed significantly
      from those of humans. The parent compounds were only detected for SARMs S4 and
      S22 and only at the first sampling time point at 3 h post administration, making
      them unsuitable as target compounds. For all three SARMs tested, the metabolite
      yielding the highest response had undergone amide hydrolysis, hydroxylation and
      sulfonation. The resulting phase II metabolites (4-nitro-3-trifluoro-methyl
      phenylamine sulfate for SARMs S1 and S4 and 4-cyano-3-trifluoro-methyl
      phenylamine sulfate for SARM S22) are proposed as analytical targets for use in
      equine doping control.

PMID- 25560999
TI  - Spatial pattern and weight of seabed marine litter in the northern and central
      Adriatic Sea.
AB  - The present study analyzes spatial distribution and typology of marine litter on
      the seabed in the FAO Geographical Sub-Area 17 (northern and central Adriatic
      Sea). Two surveys were conducted during fall 2011 and 2012 and 67 stations were
      sampled each year. Litter items were collected using the "rapido" trawl, a
      modified beam trawl commonly used by the Italian fishermen to catch flat fish and
      other benthic species. Marine litter in the catches was sorted and classified in
      6 major categories (plastic, metal, glass, rubber, wood, other). Plastic litter
      was further subdivided in 3 sub-categories based on its source: fishing nets,
      aquaculture nets and other. Plastic was dominant in terms of weight followed by
      metal and other categories. The highest concentration of litter was found close
      to the coast likely as a consequence of high coastal urbanization, river inflow
      and extensive navigation associated with the morphological and hydrological
      features of the basin. 

PMID- 25561000
TI  - Adsorption-synergic biodegradation of diesel oil in synthetic seawater by
      acclimated strains immobilized on multifunctional materials.
AB  - Using enrichment culture technique, three isolates marked as ODB-1, ODB-2 and ODB
      3, were selected from oil contaminated seawater. 16S rDNA gene sequencing
      indicated that ODB-1 affiliated with Pseudomonas sp. while ODB-2 and ODB-3
      affiliated with Brevundimonas sp. Subsequently, the bacterial cells were
      immobilized on the surface of expanded graphite (EG), expanded perlite (EP) and
      bamboo charcoal (BC). Among the three isolates, ODB-1 showed a strong binding to
      the bio-carriers through extracellular polysaccharides, while ODB-2 and ODB-3
      made the adhesion to bio-carrier through direct physical adsorption. The
      immobilized bacteria exhibited good salinity tolerance compared with the
      planktonic bacteria. Their total diesel oil removal rates were more than 85%
      after 6 days' incubation. Adsorption-biodegradation process played an important
      role in the oil-pollution remediation. EG-bacteria system was treated as a
      promising remediation method, which achieved nearly 100% removal of diesel oil.
      Thereinto, over 83% removal of diesel oil owed to biodegradation. 

PMID- 25561001
TI  - Bioremediation using Gracilaria chouae co-cultured with Sparus macrocephalus to
      manage the nitrogen and phosphorous balance in an IMTA system in Xiangshan Bay,
      China.
AB  - A cage experiment using the red alga Gracilaria chouae co-cultured with the black
      seabream Sparus macrocephalus in Xiangshan Bay, China was conducted to measure
      the nutrient flux of the integrated multi-trophic aquaculture (IMTA) system.
      Results showed that trash fish were the main nutrient input contributor and adult
      fish were the main nutrient output contributor in the system. Contents of N and P
      in adult fish accounted for 54.45% and 59.48% of N and P in trash fish and fry,
      which suggests that 45.55% of N and 40.52% of P generated by fish farming were
      released into to the water. G. chouae proved to be an efficient bioremediation
      species in this IMTA system. To balance the excess nutrients generated by the
      system, 231.09 kg of seedlings should be cultured and 5315.07 kg of adult seaweed
      should be harvested.

PMID- 25561002
TI  - Assessment of sediment contamination and sampling design in Savona Harbour,
      Italy.
AB  - A method for assessing environmental contamination in harbour sediments and
      designing the forthcoming monitoring activities in enlarged coastal ecosystems is
      proposed herein. The method is based on coupling principal component analysis of
      previous sampling campaigns with a discrete optimisation of a value for money
      function. The objective function represents the utility derived for every sum of
      money spent in sampling and chemical analysis. The method was then used to assess
      actual contamination and found to be well suited for reducing the number of
      chemicals to be searched during extended monitoring activities and identifying
      the possible sources of contamination. Data collected in Savona Harbour (Porto
      Vado), Italy, where construction of a new terminal construction is planned, were
      used to illustrate the procedure. 23 chemicals were searched for within a total
      of 213 samples in 68 sampling points during three monitoring campaigns. These
      data were used to test the procedure. Subsequently, 28 chemicals were searched
      for within 14 samples in 10 sampling points and collected data were used to
      evaluate the experimental error and to validate the proposed procedure. 

PMID- 25561003
TI  - Natural radionuclides tracing in marine surface waters along the northern coast
      of Oman Sea by combining the radioactivity analysis, oceanic currents and the
      SWAN model results.
AB  - This study aims to establish a managed sampling plan for rapid estimate of
      natural radio-nuclides diffusion in the northern coast of the Oman Sea. First,
      the natural radioactivity analysis in 36 high volume surface water samples was
      carried out using a portable high-resolution gamma-ray spectrometry. Second, the
      oceanic currents in the northern coast were investigated. Then, the third
      generation spectral SWAN model was utilized to simulate wave parameters.
      Direction of natural radioactivity propagation was coupled with the preferable
      wave vectors and oceanic currents direction that face to any marine pollution,
      these last two factors will contribute to increase or decrease of pollution in
      each grid. The results were indicated that the natural radioactivity
      concentration between the grids 8600 and 8604 is gathered in the grid 8600 and
      between the grids 8605 and 8608 is propagated toward middle part of Oman Sea. 

PMID- 25561004
TI  - Tourism and its hypersensitivity to oil spills.
AB  - The sinking of the Don Pedro merchant ship in 2007 near the island of Ibiza is a
      good example of the extreme sensitivity of the tourism sector to oil spills.
      Despite the limited scale of the spill (only some 20 tonnes), its minimal
      ecological impact, and the rapid deployment of personnel and equipment to contain
      it, the accident nonetheless caused significant economic damage to the island's
      tourism sector. This particular case demonstrates the importance of the beach as
      a factor of production in the holiday tourism sector, and the capacity of even
      small amounts of oil to render it unusable and cause heavy losses to holiday
      firms.

PMID- 25561005
TI  - Environmental fate and ecological risks of nonylphenols and bisphenol A in the
      Cape D'Aguilar Marine Reserve, Hong Kong.
AB  - Nonylphenols (NPs) and bisphenol A (BPA) are the most common endocrine disruptors
      detected in the coastal waters of Hong Kong. The Cape D'Aguilar Marine Reserve
      (CAMR), the only marine reserve in Hong Kong is close to urbanized areas, thus
      the resident marine organisms are inevitably influenced by partially treated
      wastewater from adjacent sewage treatment plants (STPs). Elevated levels of NPs
      and BPA were detected in all seawater, sediment and biota samples collected from
      the CAMR. Estrogenic activities of seawater from the CAMR, and sludge and sewage
      from a nearby STP were assessed using yeast estrogen screen assay. We found
      aromatase, estrogen receptor and vitellogenin genes in the marine medaka fish
      Oryzias melastigma were significantly up-regulated after exposure to the
      reserve's seawater. According to a tissue-residue-based probabilistic risk
      assessment, the marine species living in the CAMR are having 35% and 21% of
      chance to be at risk due to exposure to NPs and BPA, respectively. 

PMID- 25561006
TI  - Fascaplysin induces caspase mediated crosstalk between apoptosis and autophagy
      through the inhibition of PI3K/AKT/mTOR signaling cascade in human leukemia HL-60
      cells.
AB  - In this study, we for the first time explored the cellular and molecular
      mechanism of anticancer properties of fascaplysin, a marine sponge-derived
      alkaloid. Our study demonstrated that fascaplysin induced a cooperative
      interaction between apoptotic and autophagic pathways to induce cytotoxicity in
      HL-60 cells. Fascaplysin treatment not only activated pro-apoptotic events like
      PARP-1 cleavage and caspase activation but also triggered autophagy signaling as
      shown by the increased expression of LC3-II, ATG7and beclin. Interestingly, it
      was found that use of pan-caspase inhibitor completely reversed the fascaplysin
      mediated cell death as analyzed by MTT and cell cycle assays. It was observed
      that cell death as well as the expression of pro-death proteins was partially
      reversed, when key autophagy mediators ATG7 was silenced by siRNA in fascaplysin
      treated cells. Cooperative involvement of autophagy and apoptotic signaling in
      cytotoxicity was confirmed when combined silencing of pro-apototic (PARP-1) and
      autophagic (ATG-7) signaling by respective siRNA's lead to substantial rescue of
      cell death induced by fascaplysin. Although, apoptosis and autophagy are two
      independent cell death pathways, our findings provide detailed insight by which
      both the pathways acted cooperatively to elicit fascaplysin induced cell death in
      HL-60 cells. Our findings provide molecular insight into the anti-cancer
      potential of fascaplysin by showing that both autophagic and apoptotic signaling
      can work together in the induction of cell death.

PMID- 25561007
TI  - Push and pull forces in lipid raft formation: the push can be as important as the
      pull.
AB  - Nearest-neighbor recognition measurements have been made using exchangeable
      mimics of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine in the liquid-ordered (lo) and liquid-disordered (ld)
      states. In the ld phase, the net interaction between these two lipids is
      repulsive. In the lo phase, their interactions are neither attractive nor
      repulsive. These results, together with previous nearest-neighbor measurements,
      imply that the overall driving force for lipid domain formation in bilayers
      composed of high-melting lipids, low-melting lipids, and cholesterol, corresponds
      to a strong pull (attraction) between the high-melting lipids and cholesterol, a
      significant push (repulsion) between the low-melting and high-melting lipids, and
      a significant push between the low-melting lipids and cholesterol. In a broader
      context, these results provide strong support for the notion that repulsive
      forces play a major role in the formation of lipid rafts. 

PMID- 25561008
TI  - Embodied energy of construction materials: integrating human and capital energy
      into an IO-based hybrid model.
AB  - Buildings alone consume approximately 40% of the annual global energy and
      contribute indirectly to the increasing concentration of atmospheric carbon. The
      total life cycle energy use of a building is composed of embodied and operating
      energy. Embodied energy includes all energy required to manufacture and transport
      building materials, and construct, maintain, and demolish a building. For a
      systemic energy and carbon assessment of buildings, it is critical to use a whole
      life cycle approach, which takes into account the embodied as well as operating
      energy. Whereas the calculation of a building's operating energy is
      straightforward, there is a lack of a complete embodied energy calculation
      method. Although an input-output-based (IO-based) hybrid method could provide a
      complete and consistent embodied energy calculation, there are unresolved issues,
      such as an overdependence on price data and exclusion of the energy of human
      labor and capital inputs. This paper proposes a method for calculating and
      integrating the energy of labor and capital input into an IO-based hybrid method.
      The results demonstrate that the IO-based hybrid method can provide relatively
      complete results. Also, to avoid errors, the total amount of human and capital
      energy should not be excluded from the calculation. 

PMID- 25561009
TI  - Bismuth sulfide nanorods as a precision nanomedicine for in vivo multimodal
      imaging-guided photothermal therapy of tumor.
AB  - Here, we present a precision cancer nanomedicine based on Bi(2)S(3) nanorods
      (NRs) designed specifically for multispectral optoacoustic tomography (MSOT)/X
      ray computed tomography (CT)-guided photothermal therapy (PTT). The as-prepared
      Bi(2)S(3) NRs possess ideal photothermal effect and contrast enhancement in
      MSOT/CT bimodal imaging. These features make them simultaneously act as
      "satellite" and "precision targeted weapon" for the visual guide to destruction
      of tumors in vivo, realizing effective tumor destruction and metastasis
      inhibition after intravenous injection. In addition, toxicity screening confirms
      that Bi(2)S(3) NRs have well biocompatibility. This triple-modality-nanoparticle
      approach enables simultaneously precise cancer therapy and therapeutic
      monitoring.

PMID- 25561010
TI  - Chronic aortic root pressure-loading assessment model.
AB  - PURPOSE: Percutaneous placement of transcatheter prosthetic aortic valves without
      cardiopulmonary bypass (CPB) continues to gain clinical acceptance. However,
      information on pressure-loading characteristics of the aortic root/annular areas
      is limited. For this reason, we designed a preclinical model, implanting an
      aortic root load transducer with a power source/telemetry system for chronic,
      conscious, loading data acquisition. This research study was conducted to
      determine whether an animal model could accurately measure in vivo loading.
      METHODS: Preoperatively, echocardiography and magnetic resonance imaging were
      used to determine both aortic annular and sinotubular junction dimensions, as
      well as ascending aortic length. Six adult sheep were placed on CPB, aortic root
      and ascending aorta were skeletonized and the origins of both coronary ostia were
      identified. Cardiac arrest with myocardial protection with cold coronary blood
      cardioplegia was instituted. A properly sized aortic root load-sensing device,
      consisting of a transcatheter aortic valve with a ring load transducer was
      implanted via a left apical ventriculotomy. Verification of position was
      determined before closure of the ventriculotomy. Each animal was weaned from CPB,
      and closed in routine fashion with the power source of the device placed in a
      subcutaneous pocket. RESULTS: There were no operative deaths or significant
      postoperative complications. Serial pressure-load sensing assessments in a
      conscious state produced reproducible proprietary data. CONCLUSIONS: This animal
      model allowed successful serial pressure-load sensing assessment of the aortic
      root/annular areas, providing a better physiological understanding of these
      anatomical inter-relationships. This added information could aid in future device
      designs with potential improved clinical outcomes.

PMID- 25561011
TI  - Angiotensin II receptor blockade and skeletal muscle metabolism in overweight and
      obese adults with elevated blood pressure.
AB  - OBJECTIVES: Whether angiotensin II receptor blockade improves skeletal muscle
      fatty acid oxidation in overweight and obese humans is unknown. The purpose of
      the study was to test the hypothesis that the angiotensin II receptor blocker,
      olmesartan, would increase fatty acid oxidation and the activity of enzymes
      associated with oxidative metabolism in skeletal muscle of overweight and obese
      humans. METHODS: A total of 12 individuals (6 men and 6 women) aged 18-75 and
      with a body mass index ?25 kg/m2 were assigned to olmesartan or placebo for 8
      weeks in a crossover fashion. Fatty acid oxidation was measured before and after
      each intervention by counting the (14)CO2 produced from [1-(14)C] palmitic acid
      in skeletal muscle homogenates. RESULTS: Fatty acid oxidation was not
      significantly different between treatment periods at baseline and post
      intervention. In addition, the enzyme activities of citrate synthase and beta
      hydroxyacyl-coenzyme A dehydrogenase in skeletal muscle homogenates did not
      differ between treatment periods at baseline or post intervention. CONCLUSIONS:
      Treatment with olmesartan for 8 weeks does not improve fatty acid oxidation or
      the activity of enzymes associated with oxidative metabolism in skeletal muscle
      from overweight and obese individuals. Taken together, our results indicate that
      improvements in skeletal muscle metabolism are not among the additional benefits
      of olmesartan that extend beyond blood pressure reduction.

PMID- 25561012
TI  - Purification and characterization of Fab fragments with rapid reaction kinetics
      against myoglobin.
AB  - Myoglobin is an early biomarker for acute myocardial infarction. Recently, we
      isolated the antibody IgG-Myo2-7ds, which exhibits unique rapid reaction kinetics
      toward human myoglobin antigen. Antibodies with rapid dissociation kinetics are
      thought to be premature IgG forms that are produced during the early stage of in
      vivo immunization. In the present study, we identified the epitope region of the
      IgG-Myo2-7ds antibody to be the C-terminal region of myoglobin, which corresponds
      to 144-154 aa. The Fab fragment was directly purified by papain cleavage and
      protein G affinity chromatography and demonstrated kinetics of an association
      constant of 4.02 * 10(4) M(-1) s(-1) and a dissociation constant of 2.28 * 10(-2)
      s(-1), which retained the unique reaction kinetics of intact IgG-Myo2-7ds
      antibodies. Because a rapid dissociation antibody can be utilized for antibody
      recycling, the results from this study would provide a platform for the
      development of antibody engineering in potential diagnostic areas such as a
      continuous monitoring system for heart disease.

PMID- 25561013
TI  - Inhibition of Lipid Oxidation Increases Glucose Metabolism and Enhances 2-Deoxy-2
      [(18)F]Fluoro-D-Glucose Uptake in Prostate Cancer Mouse Xenografts.
AB  - PURPOSE: Prostate cancer (PCa) is the second most common cause of cancer-related
      death among men in the United States. Due to the lipid-driven metabolic phenotype
      of PCa, imaging with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) is
      suboptimal, since tumors tend to have low avidity for glucose. PROCEDURES: We
      have used the fat oxidation inhibitor etomoxir (2-[6-(4-chlorophenoxy)
      hexyl]oxirane-2-carboxylate) that targets carnitine-palmitoyl-transferase-1 (CPT
      1) to increase glucose uptake in PCa cell lines. Small hairpin RNA specific for
      CPT1A was used to confirm the glycolytic switch induced by etomoxir in vitro.
      Systemic etomoxir treatment was used to enhance [(18)F]FDG-positron emission
      tomography ([(18)F]FDG-PET) imaging in PCa xenograft mouse models in 24 h.
      RESULTS: PCa cells significantly oxidize more of circulating fatty acids than
      benign cells via CPT-1 enzyme, and blocking this lipid oxidation resulted in
      activation of the Warburg effect and enhanced [(18)F]FDG signal in PCa mouse
      models. CONCLUSIONS: Inhibition of lipid oxidation plays a major role in
      elevating glucose metabolism of PCa cells, with potential for imaging enhancement
      that could also be extended to other cancers.

PMID- 25561014
TI  - Evaluation of the Metabolic Activity of Echinococcus multilocularis in Rodents
      Using Positron Emission Tomography Tracers.
AB  - PURPOSE: 2-Deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) has been used as a
      standard clinical positron emission tomography (PET) tracer for the follow-up of
      the rare but life-threatening parasitic disease alveolar echinococcosis (AE).
      Given that the disease is endemic in many countries in the northern hemisphere
      and the diagnosis is still challenging, the aim of our study was to evaluate
      further clinically relevant PET tracers as possible diagnostic tools for AE in
      vitro and in vivo. PROCEDURES: Various clinically used PET tracers were evaluated
      in vitro and assessed in an in vivo AE animal model based on PET/magnetic
      resonance (MR) measurements. RESULTS: In vitro binding assays displayed high
      uptake of [(18)F]FDG in a cell suspension of E. multilocularis tissue, whereas 3'
      deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) and [(11)C]choline were found to be
      taken up strongly by E. multilocularis vesicles. [(18)F]FDG and [(18)F]FLT
      displayed an elevated uptake in vivo, which appeared as several foci throughout
      the parasite tissue as opposed to [(18)F]fluoro-azomycinarabinofuranoside
      ([(18)F]FAZA) and [(11)C]choline. CONCLUSIONS: Our data clearly demonstrate that
      the clinically applied PET tracer [(18)F]FDG is useful for the diagnosis and
      disease staging of AE but also has drawbacks in the assessment of currently
      inactive or metabolically weak parasitic lesions. The different tested PET
      tracers do not show the potential for the replacement or supplementation of
      current diagnostic strategies. Hence, there is still the need for novel
      diagnostic tools.

PMID- 25561015
TI  - The experience of death anxiety in Iranian war veterans: a phenomenology study.
AB  - Recognition of death anxiety experienced by patients who have survived violence
      and threats to life during war is of strong importance in delivery of best care
      for veterans experiencing health stressors. The aim of the study was to explore
      the death anxiety experience of veterans from the Iran-Iraq war. Using a
      phenomenological approach, 11 war veterans were interviewed related to death
      anxiety experiences. Four major themes included afterlife fears; alienated
      farewell; ambiguous separation; and physical dissolution. Patients who have been
      exposed to death trauma in the battlefield may carry added burden from unique
      cognitions and fears related to personal death. 

PMID- 25561017
TI  - Biodegradation kinetics of tetrahydrofuran, benzene, toluene, and ethylbenzene as
      multi-substrate by Pseudomonas oleovorans DT4.
AB  - The biodegradation kinetics of tetrahydrofuran, benzene (B), toluene (T), and
      ethylbenzene (E) were systematically investigated individually and as mixtures by
      a series of aerobic batch degradation experiments initiated by Pseudomonas
      oleovorans DT4. The Andrews model parameters, e.g., maximum specific growth rates
      (MUmax), half saturation, and substrate inhibition constant, were obtained from
      single-substrate experiments. The interaction parameters in the sum kinetics
      model (SKIP) were obtained from the dual substrates. The MUmax value of 1.01 for
      tetrahydrofuran indicated that cell growth using tetrahydrofuran as carbon source
      was faster than the growth on B (MUmax, B = 0.39) or T (MUmax, T = 0.39). The
      interactions in the dual-substrate experiments, including genhancement,
      inhibition, and co-metabolism, in the mixtures of tetrahydrofuran with B or T or
      E were identified. The degradation of the four compounds existing simultaneously
      could be predicted by the combination of SKIP and co-metabolism models. This
      study is the first to quantify the interactions between tetrahydrofuran and BTE. 

PMID- 25561018
TI  - Development a minimum data set of the information management system for burns.
AB  - BACKGROUND: Burns are the most common and destructive injuries in across of the
      world and especially in developing countries. Nevertheless, a standard tool for
      collecting the data of burn injury has not been developed yet. The purpose of
      this study was to develop a minimum data set (MDS) of the information management
      system for burns in Iran. MATERIALS AND METHODS: This descriptive and cross
      sectional study was performed in 2014. Data were collected from hospitals
      affiliated with Hormozgan and Iran University of Medical Sciences and medical
      documents centers, emergency centers and legal medicine centers located in Bandar
      Abbas city, in addition to internet access and library. Investigated documents
      were burn injury records in 2013, and documents that retrieved from the internet,
      and printed materials. Records were selected randomly based on T20-T29 categories
      from ICD-10. Data were collected using a checklist. In order to make a consensus
      about the data elements the decision Delphi technique was applied using a
      questionnaire. The content validity and reliability of questionnaire were
      assessed by expert's opinions and test-retest method, respectively. RESULTS: An
      MDS of burns was developed. This MDS divided into two categories: administrative
      and clinical with six and 17 section and 161 and 311 data elements respectively.
      CONCLUSIONS: This study showed that comprehensive and uniform data elements about
      burns do not exist in Iran. Therefore a MDS was developed for burns in Iran.
      Development of an MDS will result in standardization and effective management of
      the data through providing uniform and comprehensive data elements for burns.
      Thus, comparability of the extracted information from different analyses and
      researches will be possible in various levels. In addition, establishment of
      policies and prevention and control of burns will be possible, which results in
      the improvement of the quality of care and containment of costs.

PMID- 25561019
TI  - Validation of the Cambridge Prospective Memory Test (Hong Kong Chinese version)
      for people with stroke.
AB  - This study aimed to develop and evaluate a Hong Kong Chinese version of the
      Cambridge Prospective Memory Test (CAMPROMPT-HKCV). Thirty-three subjects at
      least one year post-stroke participated in the study. They were simultaneously
      rated on version A of the CAMPROMPT-HKCV by two testers to establish its internal
      consistency and inter-rater reliability. Raters used the parallel versions of the
      test (A and B), in rating 10 patients within 2 weeks to establish the parallel
      form reliability. Another 10 were also assessed on the same day using both
      version A of the CAMPROMPT-HKCV and the Rivermead Behavioural Memory Test-Chinese
      version (RBMT-CV) to establish concurrent validity. A new group of 40 stroke
      patients and 44 healthy controls was recruited to establish its sensitivity and
      specificity. Results indicated that test-retest reliability on time-based, event
      based and total scores, and inter-rater reliability for versions A and B of the
      test were high. Cronbach's alpha of the event-based score was higher than that of
      the time-based score. The reliability and concurrent validity of the parallel
      forms were established. There was a significant difference in performance on
      CAMPROMPT-HKCV (version A) between the stroke group and the healthy control
      group. ROC analysis showed that the ability of the cut-off CAMPROMPT-HKCV (total
      score) to differentiate PM problems was 20.5 (out of 36) with sensitivity at
      95.5% and specificity at 55.9%. Further study in developing stratified norms
      across different age groups in Chinese-speaking stroke patients is recommended. 

PMID- 25561016
TI  - The distribution of clinical phenotypes of preterm birth syndrome: implications
      for prevention.
AB  - IMPORTANCE: Preterm birth has been difficult to study and prevent because of its
      complex syndromic nature. OBJECTIVE: To identify phenotypes of preterm delivery
      syndrome in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project.
      DESIGN, SETTING, AND PARTICIPANTS: A population-based, multiethnic, cross
      sectional study conducted at 8 geographically demarcated sites in Brazil, China,
      India, Italy, Kenya, Oman, the United Kingdom, and the United States. A total of
      60,058 births over a 12-month fixed period between April 27, 2009, and March 2,
      2014. Of these, 53,871 had an ultrasonography estimate of gestational age, among
      which 5828 were preterm births (10.8%). Pregnancies were prospectively studied
      using a standardized data collection and online data management system. Newborns
      had anthropometric and clinical examinations using standardized methods and
      identical equipment and were followed up until hospital discharge. MAIN OUTCOMES
      AND MEASURES: The main study outcomes were clusters of preterm phenotypes and for
      each cluster, we analyzed signs of presentation at hospital admission, admission
      rates for neonatal intensive care for 7 days or more, and neonatal mortality
      rates. RESULTS: Twelve preterm birth clusters were identified using our
      conceptual framework. Eleven consisted of combinations of conditions known to be
      associated with preterm birth, 10 of which were dominated by a single condition.
      However, the most common single cluster (30.0% of the total preterm cases; n =
      1747) was not associated with any severe maternal, fetal, or placental condition
      that was clinically detectable based on the information available; within this
      cluster, many cases were caregiver initiated. Only 22% (n = 1284) of all the
      preterm births occurred spontaneously without any of these severe conditions.
      Maternal presentation on hospital admission, newborn anthropometry, and risk for
      death before hospital discharge or admission for 7 or more days to a neonatal
      intensive care unit, none of which were used to construct the clusters, also
      differed according to the identified phenotypes. The prevalence of preterm birth
      ranged from 8.2% in Muscat, Oman, and Oxford, England, to 16.6% in Seattle,
      Washington. CONCLUSIONS AND RELEVANCE: We identified 12 preterm birth phenotypes
      associated with different patterns of neonatal outcomes. In 22% of all preterm
      births, parturition started spontaneously and was not associated with any of the
      phenotypic conditions considered. We believe these results contribute to an
      improved understanding of this complex syndrome and provide an empirical basis to
      focus research on a more homogenous set of phenotypes.

PMID- 25561020
TI  - Utilisation of preoperative imaging for muscle-invasive bladder cancer: a
      population-based study.
AB  - OBJECTIVE: To test the hypotheses that: (i) use of preoperative imaging for
      muscle-invasive bladder cancer (MIBC) conforms to practice guidelines; (ii)
      preoperative imaging, through more accurate staging is associated with improved
      outcomes. PATIENT AND METHODS: In this population-based cohort study, records of
      treatment were linked to the Ontario Cancer Registry to identify all patients
      with MIBC treated with cystectomy from 1994 to 2008. Utilisation of chest,
      abdomen-pelvis and bone imaging were evaluated. Trends were evaluated over time.
      Logistic regression was used to analyse factors associated with utilisation. Cox
      model analyses were used to explore associations between imaging and survival.
      RESULTS: In all, 2 802 patients with MIBC underwent cystectomy during 1994-2008.
      Over the three 5-year study periods there was an increase in the proportion of
      patients having preoperative: chest X-ray (55%, 64%, 63%, P < 0.001), computed
      tomography (CT) of the chest (10%, 10%, 21%, P < 0.001), bone scan (30%, 34%,
      36%; P = 0.04) and CT/magnetic resonance imaging/ultrasonography abdomen/pelvis
      (80%, 87%, 90%, P <= 0.001). Use of chest imaging was associated with age (odds
      ratio [OR] 1.24-1.59 compared with the youngest age group), N-stage (OR 0.79 for
      the NX group compared with the N+ group), surgeon volume (OR 0.47-0.53 compared
      with the highest volume quartile) and geographic region (OR 0.47-2.19 compared
      with the largest region). Use of bone scan was associated with N-stage (OR 0.57
      for the NX group compared with the N+ group) and geographic region (OR 0.71-1.34
      compared with the largest region). In adjusted analyses, we found that patients
      who did not have preoperative chest imaging had inferior overall survival (OS),
      hazard ratio (HR) 1.12 (95% confidence interval [CI] 1.01-1.25) but not cancer
      specific survival (CSS), HR 1.09 (95% CI 0.97-1.22); those who did not have
      preoperative bone scan had inferior OS (HR 1.11, 95% CI 1.01-1.22) and CSS (HR
      1.09, 95% CI 1.01-1.25). Survival in the abdomen and pelvis imaging group was not
      evaluated due to lack of a suitable control group. CONCLUSION: In routine
      clinical practice there is considerable variation in use of preoperative chest,
      body, and bone imaging. Preoperative chest and bone imaging is associated with
      improved outcomes; this association probably reflects better patient selection
      for cystectomy.

PMID- 25561021
TI  - Transition-metal-mediated uncaging in living human cells-an emerging alternative
      to photolabile protecting groups.
AB  - Photolabile protecting groups have been widely used for activation strategies of
      caged substrates within living cells. However, an alternative uncaging method in
      which, instead of light, chemical compounds are used as activators (chemical
      uncaging) is still in its infancy. The recent advances in bioorthogonal reactions
      mediated by transition metals have shown that bioorthogonal catalysts have the
      potential to yield such a chemical activator. By now we have seen transition
      metal compounds that activate caged enzymes, toxigenic prodrugs and other small
      molecules such as fluorophores within living human cells. In this review we will
      focus on metal catalysts based on palladium, ruthenium and iron and we will
      mainly discuss their biocompatibility and catalytic efficiency in uncaging
      reactions within biological environments. 

PMID- 25561022
TI  - Shb deficiency in endothelium but not in leucocytes is responsible for impaired
      vascular performance during hindlimb ischaemia.
AB  - AIM: Myeloid cells have been suggested to participate in angiogenesis and
      regulation of vascular function. Shb-deficient mice display both vascular and
      myeloid cell abnormalities with possible consequences for recovery after hindlimb
      ischaemia. This study was conducted in order to assess the contribution of Shb
      deficiency in myeloid cells to impaired vascular function in ischaemia. METHODS:
      Wild type and Shb-deficient mice were subjected to peritoneal vascular
      endothelial growth factor A (VEGFA) followed by intraperitoneal lavage, after
      which blood and peritoneal cells were stained for myeloid markers. VEGFA-induced
      leucocyte recruitment to cremaster muscle was investigated using intravital
      microscopy of both mouse strains. Blood flow after femoral artery ligation was
      determined on chimeric mice after bone marrow transplantation. RESULTS: No
      differences in neutrophil numbers or cell surface phenotypes were detected.
      Moreover, neutrophil extravasation in VEGFA-activated cremaster muscle was
      unaffected by Shb deficiency. However, blood and peritoneal CXCR4+
      monocytes/macrophages were reduced in response to intraperitoneal VEGFA but not
      lipopolysaccharide (LPS) in the absence of Shb. Furthermore, the macrophage
      population in ischaemic muscle was unaffected by Shb deficiency after 2 days but
      reduced 7 days after injury. The bone marrow transplantation experiments revealed
      that mice with wild type vasculature showed better blood flow than those with Shb
      deficient vasculature irrespective of leucocyte genotype. CONCLUSION: The
      observed aberrations in myeloid cell properties in Shb-deficient mice are likely
      consequences of an abnormal vascular compartment and are not responsible for
      reduced muscle blood flow. Structural vascular abnormalities seem to be the
      primary cause of poor vascular performance under provoked vascular stress in this
      genetic model.

PMID- 25561024
TI  - Should insulin resistance be screened in lean hirsute women?
AB  - The role of insulin resistance (IR) is well-documented in obese women with
      polycystic ovary syndrome (PCOS). Controversies exist concerning the presence of
      IR in idiopathic hirsutism (IH) or if it is a manifestation of high body mass
      index (BMI). We aimed to investigate the presence/absence of IR in lean hirsute
      women. One-hundred fifty-one lean women with hirsutism [96 PCOS (group 1) and 55
      IH (group 2)] and 58 age-and BMI-matched healthy controls (group 3) were
      recruited in the study (mean age 25.21 +/- 6.1 versus 26.26 +/- 4.6years; BMI
      21.79 +/- 1.7 versus 22.02 +/- 2.2 kg/m(2), respectively). Significantly higher
      insulin and HOMA-IR, and significantly lower fasting glucose insulin ratio
      (FGIR), quantitative insulin sensitivity check index (QUICKI), reciprocal
      insulin, and Raynaud index were detected in groups 1 and 2 than in group 3 (p <
      0.05). These IR indices were similar between groups 1 and 2. The number of
      patients with IR (HOMA-IR > 2, FGIR < 7.2, or QUICKI < 0.357) was significantly
      higher in groups 1 and 2 than in group 3, but was similar between groups 1 and 2.
      A higher frequency of IR occurs in lean hirsute women regardless of they having
      PCOS or IH. IR may contribute to aetiopathogenesis of IH, or may cause some
      metabolic abnormalities in these patients. 

PMID- 25561023
TI  - Molecular determinants of alpha-synuclein mutants' oligomerization and membrane
      interactions.
AB  - Parkinson's disease (PD) is associated with the formation of toxic alpha
      synuclein oligomers that can penetrate the cell membrane. Familial forms of PD
      are caused by the point mutations A53T, A30P, E46K, and H50Q. Artificial point
      mutations E35K and E57K also increase oligomerization and pore formation. We
      generated structural conformations of alpha-synuclein and the above-mentioned
      mutants using molecular dynamics. We elucidated four main regions in these
      conformers contacting the membrane and found that the region including residues
      39-45 (Zone2) may have maximum membrane penetration. E57K mutant had the highest
      rate of interaction with the membrane, followed by A53T, E46K, and E35K mutants
      and wild type (wt) alpha-synuclein. The mutant A30P had the smallest percentage
      of conformers that contact the membrane by Zone 2 than all other mutants and wt
      alpha-synuclein. These results were confirmed experimentally in vitro. We
      identified the key amino acids that can interact with the membrane (Y38, E62, and
      N65 (first hydrophilic layer); E104, E105, and D115 (second hydrophilic layer),
      and V15 and V26 (central hydrophobic layer)) and the residues that are involved
      in the interprotein contacts (L38, V48, V49, Q62, and T64). Understanding the
      molecular interactions of alpha-synuclein mutants is important for the design of
      compounds blocking the formation of toxic oligomers. 

PMID- 25561025
TI  - The responses of hypothalamic NPY and OBRb mRNA expression to food deprivation
      develop during the neonatal-prepubertal period and exhibit gender differences in
      rats.
AB  - Neuropeptide Y (NPY) is an important hypothalamic orexigenic neuropeptide that
      acts in the brain. It has been established that the fasting-induced up-regulation
      of NPY expression is mainly caused by a reduction in the activity of leptin,
      which is a hormone secreted by adipose tissue. We have reported that in female
      rats hypothalamic NPY mRNA expression does not respond to fasting during the
      early neonatal period, but subsequently becomes sensitive to it later in the
      neonatal period. In this study, we compared the developmental changes in the
      responses of NPY and leptin expression to fasting between male and female rats
      during the neonatal to pre-pubertal period. Fasting was induced by maternal
      deprivation during the pre-weaning period (postnatal days 10 and 20) and by food
      deprivation during the post-weaning period (postnatal day 30). Hypothalamic NPY
      mRNA expression was not affected by fasting on postnatal day 10, whereas it was
      increased by fasting on postnatal day 20 and 30 in both males and females. On the
      other hand, the serum leptin level was decreased by fasting at all examined ages
      in both sexes. Namely, hypothalamic NPY mRNA expression was not correlated with
      the reduction in the serum leptin level at postnatal day 10 in either sex. Under
      the fasted conditions, the hypothalamic NPY mRNA levels of the males were higher
      than those of the females on postnatal days 20 and 30, whereas no such
      differences were observed under the normal nourishment conditions. The serum
      leptin levels observed under the fasted conditions did not differ between males
      and females at any examined age. These results suggest that some hypothalamic NPY
      functions develop during the neonatal period and that there is no major
      difference between the sexes with regard to the time when NPY neurons become
      sensitive to fasting. They also indicate that hypothalamic NPY expression is more
      sensitive to under-nutrition in male rats than in female rats, at least during
      the pre-pubertal period. 

PMID- 25561026
TI  - Eudragit nanoparticles loaded with silybin: a detailed study of preparation,
      freeze-drying condition and in vitro/in vivo evaluation.
AB  - The objective of this work was use of silybin nanoparticles in treatment of
      ulcerative colitis (UC). Eudragit RL PO nanoparticles loaded with silybin were
      produced using solvent-evaporation emulsification technique. Then, they were
      coated by Eudragit FS30D. Drug release was studied in different physiological
      environments. Colitis was induced by 4% of acetic acid in rats which received
      freeze-dried nanoparticles of silybin (75 mg/kg/day), dexamethasone (1
      mg/kg/day), blank nanoparticles and normal saline orally for 5 days. Then
      macroscopic, histopathological evaluation and biochemical analysis, including
      myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) levels in colon tissues were determined using enzyme-linked
      immunosorbent assay (ELISA) kits. Macroscopic and histopathological scores were
      improved by the optimised nanoparticles. The optimised nanoparticles had a
      particle size of 109 +/- 6 nm, zeta potential of 15.4 +/- 2 mV, loading
      efficiency of 98.3 +/- 12% and release efficiency of 40.8 +/- 5.5% at 24 h. TNF
      alpha, IL-6 and MPO activity were reduced significantly by nanoparticles compared
      to control group (p < 0.05). 

PMID- 25561027
TI  - Following the dynamics of matter with femtosecond precision using the X-ray
      streaking method.
AB  - X-ray Free Electron Lasers (FELs) can produce extremely intense and very short
      pulses, down to below 10 femtoseconds (fs). Among the key applications are
      ultrafast time-resolved studies of dynamics of matter by observing responses to
      fast excitation pulses in a pump-probe manner. Detectors with sufficient time
      resolution for observing these processes are not available. Therefore, such
      experiments typically measure a sample's full dynamics by repeating multiple pump
      probe cycles at different delay times. This conventional method assumes that the
      sample returns to an identical or very similar state after each cycle. Here we
      describe a novel approach that can provide a time trace of responses following a
      single excitation pulse, jitter-free, with fs timing precision. We demonstrate,
      in an X-ray diffraction experiment, how it can be applied to the investigation of
      ultrafast irreversible processes. 

PMID- 25561029
TI  - Pharmacokinetic modelling of dialytic clearance in a case of acyclovir
      intoxication.

PMID- 25561031
TI  - The molecular therapy family: past, present, and future.

PMID- 25561030
TI  - Genetic characterisation of drug resistance and clonal dynamics of Acinetobacter
      baumannii in a hospital setting in Mexico.
AB  - The aim of this study was to determine the clinical characteristics, molecular
      epidemiology and biofilm production of Acinetobacter baumannii clinical isolates
      obtained from a tertiary-care hospital in Mexico. Clinical isolates of A.
      baumannii (n=152) isolated from 2007 to 2012 were included. Clonal diversity was
      analysed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence
      typing (MLST). Antimicrobial susceptibility was determined using the broth
      microdilution method. IMP, VIM, NDM and OXA-type genes were screened by PCR.
      Biofilm production was analysed using the crystal violet method. Mortality
      attributable to A. baumannii infection was 14.5%. Fifty-four clones were
      detected, of which five predominated. MLST results showed three new sequence
      types and two reported sequence types. More than 86% of the isolates were
      resistant to ciprofloxacin, ceftazidime and cefotaxime. Furthermore, 50.7% and
      35.5% of the isolates were resistant to imipenem and meropenem, respectively. Of
      the isolates evaluated, 28.3% and 25.7% were positive for the blaOXA-58 and
      blaOXA-72 genes, respectively. Biofilm production was associated with resistance
      to imipenem (P=0.002). 

PMID- 25561028
TI  - Behavioral flexibility in rats and mice: contributions of distinct frontocortical
      regions.
AB  - Research examining the contribution of genetics to behavior is increasingly
      focused on higher order behavioral and cognitive processes including the ability
      to modify behaviors when environmental demands change. The frontal cortices of
      mammals, including rodents, subserve a diverse set of behavioral and cognitive
      functions including motor planning, social behavior, evaluation of expected
      outcomes and working memory, which may be particularly sensitive to genetic
      factors and interactions with experience (e.g. stress). Behavioral flexibility is
      a core attribute of these functions. This review orients readers to the current
      landscape of the literature on the frontocortical bases of behavioral flexibility
      in rodent laboratory experiments. Studies are divided into three broad
      categories: reversal learning, inhibitory learning and set-shifting. Functional
      dissociations within the broader scope of behavioral flexibility are reviewed,
      followed by discussion of the associations between specific components of frontal
      cortex and specific aspects of relevant behavioral processes. Finally, the
      authors identify open questions that need to be addressed to better establish the
      constituents of frontal cortex underlying behavioral flexibility. 

PMID- 25561035
TI  - Corrigendum to "Use of miRNA response sequences to block off-target replication
      and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV".

PMID- 25561034
TI  - Hitting the target without pulling the trigger.

PMID- 25561036
TI  - Introduction. The whole is not only more than but very different than the sum of
      its parts.

PMID- 25561039
TI  - A 24-day-old neonate with annular plaques on the scalp.

PMID- 25561040
TI  - Healthy school lunches.

PMID- 25561042
TI  - A prospective examination of whether childhood sexual abuse predicts subsequent
      sexual offending.
AB  - IMPORTANCE: Childhood sexual abuse has been assumed to increase the risk for
      sexual offending. However, despite methodological limitations of prior research,
      public policies and clinical practice have been based on this assumption.
      OBJECTIVE: To empirically examine the commonly held belief that sexually abused
      children grow up to become sexual offenders and specialize in sex crimes. DESIGN,
      SETTING, AND PARTICIPANTS: This prospective cohort study and archival records
      check included cases and control individuals originally from a metropolitan
      county in the Midwest. Children with substantiated cases of physical and sexual
      abuse and neglect (aged 0-11 years) were matched with children without such
      histories on the basis of age, sex, race/ethnicity, and approximate family social
      class (908 cases and 667 control individuals). Both groups were followed up into
      adulthood (mean age, 51 years). The court cases were from 1967 to 1971; the
      follow-up extended to 2013. MAIN OUTCOMES AND MEASURES: Criminal history
      information was collected from federal and state law enforcement agency records
      at 3 points in time and from state sex offender registries. RESULTS: Overall,
      individuals with histories of childhood abuse and neglect were at increased risk
      for being arrested for a sex crime compared with control individuals (adjusted
      odds ratio [AOR], 2.17; 95% CI, 1.38-3.40), controlling for age, sex, and
      race/ethnicity. Specifically, individuals with histories of physical abuse (AOR,
      2.06; 95% CI, 1.02-4.16) and neglect (AOR, 2.21; 95% CI, 1.39-3.51) were at
      significantly increased risk for arrest for sex offenses, whereas for sexual
      abuse, the AOR (2.13; 95% CI, 0.83-5.47) did not reach significance. Physically
      abused and neglected males (not females) were at increased risk and physically
      abused males also had a higher mean number of sex crime arrests compared with
      control individuals. The results did not provide support for sex crime
      specialization. CONCLUSIONS AND RELEVANCE: The widespread belief that sexually
      abused children are uniquely at risk to become sex offenders was not supported by
      prospective empirical evidence. These new findings suggest that early
      intervention programs should target children with histories of physical abuse and
      neglect. They also indicate that existing policies and practices specifically
      directed at future risk for sex offending for sexually abused children may
      warrant reevaluation.

PMID- 25561041
TI  - Effect of expanding medicaid for parents on children's health insurance coverage:
      lessons from the Oregon experiment.
AB  - IMPORTANCE: In the United States, health insurance is not universal.
      Observational studies show an association between uninsured parents and children.
      This association persisted even after expansions in child-only public health
      insurance. Oregon's randomized Medicaid expansion for adults, known as the Oregon
      Experiment, created a rare opportunity to assess causality between parent and
      child coverage. OBJECTIVE: To estimate the effect on a child's health insurance
      coverage status when (1) a parent randomly gains access to health insurance and
      (2) a parent obtains coverage. DESIGN, SETTING, AND PARTICIPANTS: Oregon
      Experiment randomized natural experiment assessing the results of Oregon's 2008
      Medicaid expansion. We used generalized estimating equation models to examine the
      longitudinal effect of a parent randomly selected to apply for Medicaid on their
      child's Medicaid or Children's Health Insurance Program (CHIP) coverage (intent
      to-treat analyses). We used per-protocol analyses to understand the impact on
      children's coverage when a parent was randomly selected to apply for and obtained
      Medicaid. Participants included 14409 children aged 2 to 18 years whose parents
      participated in the Oregon Experiment. EXPOSURES: For intent-to-treat analyses,
      the date a parent was selected to apply for Medicaid was considered the date the
      child was exposed to the intervention. In per-protocol analyses, exposure was
      defined as whether a selected parent obtained Medicaid. MAIN OUTCOMES AND
      MEASURES: Children's Medicaid or CHIP coverage, assessed monthly and in 6-month
      intervals relative to their parent's selection date. RESULTS: In the immediate
      period after selection, children whose parents were selected to apply
      significantly increased from 3830 (61.4%) to 4152 (66.6%) compared with a
      nonsignificant change from 5049 (61.8%) to 5044 (61.7%) for children whose
      parents were not selected to apply. Children whose parents were randomly selected
      to apply for Medicaid had 18% higher odds of being covered in the first 6 months
      after parent's selection compared with children whose parents were not selected
      (adjusted odds ratio [AOR]=1.18; 95% CI, 1.10-1.27). The effect remained
      significant during months 7 to 12 (AOR=1.11; 95% CI, 1.03-1.19); months 13 to 18
      showed a positive but not significant effect (AOR=1.07; 95% CI, 0.99-1.14).
      Children whose parents were selected and obtained coverage had more than double
      the odds of having coverage compared with children whose parents were not
      selected and did not gain coverage (AOR=2.37; 95% CI, 2.14-2.64). CONCLUSIONS AND
      RELEVANCE: Children's odds of having Medicaid or CHIP coverage increased when
      their parents were randomly selected to apply for Medicaid. Children whose
      parents were selected and subsequently obtained coverage benefited most. This
      study demonstrates a causal link between parents' access to Medicaid coverage and
      their children's coverage.

PMID- 25561043
TI  - Why it matters to know the relationship between child abuse and neglect and
      sexual offending.

PMID- 25561044
TI  - Basic concepts and potential applications of genetics and genomics for
      cardiovascular and stroke clinicians: a scientific statement from the American
      Heart Association.

PMID- 25561046
TI  - Circulating cholesteryl ester transfer protein and coronary heart disease:
      mendelian randomization meta-analysis.
AB  - BACKGROUND: The cholesteryl ester transfer protein (CETP) plays a central role in
      reverse cholesterol transport. Currently, it remains unresolved whether
      circulating CETP is causally associated with coronary heart disease (CHD). We
      aimed to investigate this causal association using CETP gene rs708272
      polymorphism as an instrument in a Mendelian randomization meta-analysis. METHODS
      AND RESULTS: We searched PubMed and EMBASE before May 2014. Data and study
      quality were assessed in duplicate. Thirty-four articles (17 813 CHD patients and
      22 203 controls) were qualified. Overall analyses revealed a significant
      association of rs708272-B1 allele with a reduced CHD risk compared with B2 allele
      under allelic (odds ratio and 95% confidence interval: 0.87 and 0.82-0.92;
      P<0.001), homozygous genotypic (0.74 and 0.66-0.83; P<0.001), and dominant (0.87
      and 0.80-0.94; P<0.001) models. Carriers of rs708272-B1B1 genotype (weighted mean
      difference and 95% confidence interval: -0.21 and -0.41 to 0.00 MUg/dL; P=0.052)
      or B1 allele (-0.15 and -0.30 to 0.00 MUg/dL; P=0.056) had a marginally lower
      circulating CETP level compared with B2B2 genotype carriers. In Mendelian
      randomization analysis, there was a 25% (odds ratio and 95% confidence interval:
      0.75 and 0.19-0.91) and a 17% (0.83 and 0.41-0.96) significantly reduced risk of
      CHD by a reduction of 0.2 MUg/mL in circulating CETP for the comparison of B1B1
      genotype and B1 allele with B2B2 genotype, respectively. There were low
      probabilities of publication bias. CONCLUSIONS: Our findings demonstrate that the
      long-term genetically reduced circulating CETP might be causally associated with
      the low risk of CHD.

PMID- 25561045
TI  - 22q11.2 deletion status and disease burden in children and adolescents with
      tetralogy of Fallot.
AB  - BACKGROUND: Patients with repaired tetralogy of Fallot experience variable
      outcomes for reasons that are incompletely understood. We hypothesize that
      genetic variants contribute to this variability. We sought to investigate the
      association of 22q11.2 deletion status with clinical outcome in patients with
      repaired tetralogy of Fallot. METHODS AND RESULTS: We performed a cross-sectional
      study of tetralogy of Fallot subjects who were tested for 22q11.2 deletion, and
      underwent cardiac magnetic resonance, exercise stress test, and review of medical
      history. We studied 165 subjects (12.3+/-3.1 years), of which 30 (18%) had
      22q11.2 deletion syndrome (22q11.2DS). Overall, by cardiac magnetic resonance the
      right ventricular ejection fraction was 60+/-8%, pulmonary regurgitant fraction
      was 34+/-17%, and right ventricular end-diastolic volume was 114+/-39 cc/m(2). On
      exercise stress test, maximum oxygen consumption was 76+/-16% predicted. Despite
      comparable right ventricular function and pulmonary regurgitant fraction, on
      exercise stress test the 22q11.2DS had significantly lower percent predicted:
      forced vital capacity (61.5+/-16 versus 80.5+/-14; P<0.0001), maximum oxygen
      consumption (61+/-17 versus 80+/-12; P<0.0001), and work (64+/-18 versus 86+/-22,
      P=0.0002). Similarly, the 22q11.2DS experienced more hospitalizations (6.5 [5-10]
      versus 3 [2-5]; P<0.0001), saw more specialists (3.5 [2-9] versus 0 [0-12];
      P<0.0001), and used >=1 medications (67% versus 34%; P<0.001). CONCLUSIONS:
      22q11.2DS is associated with restrictive lung disease, worse aerobic capacity,
      and increased morbidity, and may explain some of the clinical variability seen in
      tetralogy of Fallot. These findings may provide avenues for intervention to
      improve outcomes, and should be re-evaluated longitudinally because these
      associations may become more pronounced with time.

PMID- 25561048
TI  - Biodegradability and swelling capacity of kaolin based chitosan-g-PHEMA
      nanocomposite hydrogel.
AB  - Chitosan, a natural biopolymer, obtained by alkaline deacetylation of chitin,
      exhibits excellent biological properties such as biodegradability, immunological
      and antibacterial activity. Recently, there has been a growing interest in the
      chemical modification of chitosan in order to widen its applications. The
      chemical modification of chitosan has been achieved via grafting of monomer, 2
      hydroxyethyl methacrylate (HEMA) in the presence of the initiator, ammonium
      persulfate (APS) and kaolin was added to improve the mechanical strength of the
      newly developed nanocomposites hydrogel. The so prepared grafted nanocomposites
      hydrogel was characterized by FTIR, XRD, SEM, TEM and TGA. The equilibrium water
      content (EWC) of the samples were measured at different pH ranges 6.5-8.0 and
      found optimum at pH 7.5 for biomedical applications. Further, the
      biodegradability of the samples was studied at different time intervals from 15
      days to 1 year but, the kaolin based nanohydrogels exhibited good
      biodegradability. 

PMID- 25561049
TI  - Physicochemical and release properties of carboxymethylated starches of Dioscorea
      from Jharkhand.
AB  - Increasing demand and considerable attention to the non-conventional sources of
      starches leads to explore new sources. Starches of Dioscorea (Da1 and Da2) from
      Jharkhand, North Eastern region of India have been studied for its
      physicochemical properties. An attempt has been made to study the
      carboxymethylated derivatives of starches from two varieties of Dioscorea of this
      region. Different concentration of monochloroacetate was used to study the effect
      of degree of substitution (DS) on the physicochemical properties of starches. A
      considerable effect of DS was noticed on the ash content, amylose content, water
      holding capacity, swelling and solubility power of carboxymethylated derivatives.
      Morphological studies showed the increase in the deformation of structure of the
      starch granule with an increase in the degree of substitution. FTIR confirmed the
      carboxymethylation reaction. TGA data of carboxymethylated starches revealed the
      stability to the temperature. Micromeritics of starch powder and granules showed
      the value which makes these starches to be utilized as an excipient. With the
      increase in DS, the % release of drug was found to be decreased. This further
      makes the carboxymethyl derivatives of Dioscorea a good source to be used as an
      excipient for sustained release formulations. 

PMID- 25561047
TI  - Genome-wide association analysis of plasma B-type natriuretic peptide in blacks:
      the Jackson Heart Study.
AB  - BACKGROUND: Numerous experimental studies suggest that B-type natriuretic peptide
      (BNP) is cardioprotective; however, in clinical studies, higher plasma BNP
      concentrations have been associated with incident cardiovascular disease and
      higher left ventricular mass. Genetic association studies may allow us to
      determine the true causal directions without confounding by compensatory
      mechanisms. METHODS AND RESULTS: We performed a meta-analysis of 2 genome-wide
      association results from a total of 2790 blacks. We assumed an additive genetic
      model in an association analysis of imputed 2.5 million single-nucleotide
      polymorphism dosages with residuals generated from multivariable-adjusted
      logarithmically transformed BNP controlling for relevant covariates and
      population stratification. Two loci were genome-wide significant, a candidate
      gene locus NPPB (rs198389, P=1.18*10(-09)) and a novel missense variant in the
      KLKB1 locus (rs3733402, P=1.75*10(-11)) that explained 0.4% and 1.9% of variation
      in log BNP concentration, respectively. The observed increase in BNP
      concentration was proportional to the number of effect allele copies, and an
      average of 8.1 pg/mL increase was associated with 2 allele copies. In a companion
      study, single-nucleotide polymorphisms in this loci were cross-checked with
      genome-wide association results for the aldosterone/renin ratio in individuals of
      European ancestry, and rs3733402 was genome-wide significant (P<5.0*10(-8)),
      suggesting possible shared genetic architecture for these 2 pathways. Other
      statistically significant relations for these single-nucleotide polymorphisms
      included the following: rs198389 with systolic blood pressure in blacks (COGENT
      consortium) and rs198389 and rs3733402 with left ventricular mass in whites
      (EchoGEN consortium). CONCLUSIONS: These findings improve our knowledge of the
      genetic basis of BNP variation in blacks, demonstrate a possible shared allelic
      architecture for BNP with aldosterone-renin ratio, and motivate further studies
      of underlying mechanisms.

PMID- 25561050
TI  - Nucleic acid aptamers in cancer research, diagnosis and therapy.
AB  - Aptamers are single-stranded DNA or RNA oligomers, identified from a random
      sequence pool, with the ability to form unique and versatile tertiary structures
      that bind to cognate molecules with superior specificity. Their small size,
      excellent chemical stability and low immunogenicity enable them to rival
      antibodies in cancer imaging and therapy applications. Their facile chemical
      synthesis, versatility in structural design and engineering, and the ability for
      site-specific modifications with functional moieties make aptamers excellent
      recognition motifs for cancer biomarker discovery and detection. Moreover,
      aptamers can be selected or engineered to regulate cancer protein functions, as
      well as to guide anti-cancer drug design or screening. This review summarizes
      their applications in cancer, including cancer biomarker discovery and detection,
      cancer imaging, cancer therapy, and anti-cancer drug discovery. Although relevant
      applications are relatively new, the significant progress achieved has
      demonstrated that aptamers can be promising players in cancer research. 

PMID- 25561051
TI  - Toll-like receptor 9 promoter polymorphism as a predictive factor of narrow-band
      UVB phototherapy response in patients with psoriasis.
AB  - BACKGROUND: Prediction of response to ultraviolet B (UVB) phototherapy in
      psoriatic patients mainly relies on clinical criteria, although some genetic
      predictors have been identified. Toll-like receptors (TLRs) have been involved in
      psoriasis pathogenesis through activation of the innate immune system. Their
      polymorphisms may condition not only the clinical profile of psoriasis but also
      the response to therapy. METHODS: We analyzed the role of functional single
      nucleotide polymorphisms (SNPs) of TLR2, 5, 4, and 9 in clinical response to a
      standard narrow-band UVB (NBUVB) therapy in 39 patients with moderate to severe
      psoriasis. RESULTS: We found a significant relationship between TLR9-1486T/C SNP
      variants and a better response to NBUVB phototherapy. Patients with TC and CC
      genotype showed a higher improvement of Psoriasis Area and Severity Index (PASI)
      than patients with TT genotype. Results of multivariate analysis indicate that
      the differences in PASI improvement at the end of phototherapy attributed to TRL9
      SNP genotype were not dependent on the patients' phototype, age, gender, body
      mass index, basal PASI, or disease evolution. CONCLUSIONS: We describe a
      functional genetic variant in TLR9 gene that might affect the susceptibility to
      antipsoriatic treatment. The search of genetic predictive factors may be helpful
      in therapy selection and optimization of therapeutic regimes in psoriatic
      patients.

PMID- 25561052
TI  - Identification of Candida tropicalis BH-6 and synergistic effect with Pantoea
      agglomerans BH-18 on hydrogen production in marine culture.
AB  - A marine yeast was isolated from mangrove sludge and named Candida tropicalis BH
      6. The optimum temperature and the initial pH value for growth of the isolated
      strain were 37  degrees C and 5.0, respectively. The strain had high salt
      tolerance and could survive at NaCl concentrations of 0-6 %. Additionally, the
      yield of hydrogen production by C. tropicalis BH-6 was only 66.30 ml/l. However,
      when the yeast was mixed with Pantoea agglomerans BH-18, hydrogen production
      increased significantly to a maximum of 1707.5 ml/l, which was 36.94 and 247.54 %
      higher than the monoculture of P. agglomerans BH-18 and C. tropicalis BH-6,
      respectively. Taken together, these results revealed that in mixed culture, the
      yeast strain isolated from the same ecosystem as P. agglomerans BH-18 likely
      consumed the organic acids produced by fermentation, thus eliminating the factor
      inhibiting hydrogen production by P. agglomerans BH-18. As a result, the yield of
      hydrogen production during mixed culture increased significantly.

PMID- 25561053
TI  - Differential display of antioxidants in mitigating adverse effects of UV-B
      radiation in Nostoc muscorum and Phormidium foveolarum photoacclimated to
      different irradiances.
AB  - The response of UV-B radiation (UV-BL; 0.5) and (UV-BH; 1.5 MUmol m(-2) s(-1))
      was investigated in two cyanobacteria--Nostoc muscorum and Phormidium foveolarum-
      preacclimated to low, normal, and high (LL; 15 +/- 0.5, NL; 75 +/- 3.5, and HL;
      225 +/- 5.5 MUmol photon m(-2) s(-1), respectively) light intensities.
      Acclimation to HL stimulated growth over the control; however, both UV-B doses
      induced decline in growth of both cyanobacteria. UV-B-induced decline was maximum
      in LL acclimated cells which was in consonance with the results for chlorophyll
      content. LL acclimation led to an increase in phycocyanin content. Carotenoids
      content was maximum in HL acclimated (UV-B untreated and treated) cells of N.
      muscorum and P. foveolarum. Maximum stimulation in SOR and H2O2 levels was
      observed under LL + UV-BH treatment which was correlated with inefficient
      antioxidative mechanism (SOD, CAT, POD, and GST) in these cells. MDA and RCG
      contents also showed a similar trend. Mitigation of UV-B-induced stress response
      could be established in HL acclimated cells due to the concerted and differential
      display of enzymatic and nonenzymatic antioxidants in them. P. foveolarum proved
      to be more resistant than N. muscorum under the studied test conditions.

PMID- 25561054
TI  - Production of lactic acid from the mixture of softwood pre-hydrolysate and paper
      mill sludge by simultaneous saccharification and fermentation.
AB  - Paper mill sludge is a solid waste material composed of pulp residues and ash
      generated from pulping and paper making process. The carbohydrate portion of the
      sludges from Kraft/Recycle paper mill has chemical and physical characteristics
      similar to those of commercial wood pulp. Because of its high carbohydrate
      content and well-dispersed structure, the sludge can be biologically converted to
      value-added products without pretreatment. In bioconversion of solid feedstock
      such as paper mill sludge, a certain amount of water must be present to attain
      fluidity. In this study, hemicellulose pre-hydrolysate, in place of water, was
      added to the sludge to increase the concentration of the final product. Pre
      hydrolysate was obtained by hot-water treatment of pine wood in which the total
      sugar concentration reached 4 wt.%. The mixture was processed by simultaneous
      saccharification and fermentation (SSF) using enzymes (cellulase and pectinase)
      and Lactobacillus rhamnosus (ATCC-10863). Pectinase was added to hydrolyze
      mannose oligomers in the pre-hydrolysate to monomers. During the SSF of the
      mixture, calcium carbonate in the paper sludge acted as a buffer, yielding
      calcium lactate as the final product. External pH control was unnecessary due to
      the buffer action of calcium carbonate that maintained the pH near optimum for
      the SSF. The lactic acid yield in the range of 80-90 % of the theoretical maximum
      was obtained. Use of the mixed feed of pre-hydrolysate and pulp mill sludges in
      the SSF raised the product concentration to 60 g of lactate/L.

PMID- 25561055
TI  - Comparison of two different reactive dye immobilized poly(hydroxyethyl
      methacrylate) cryogel discs for purification of lysozyme.
AB  - In this study, cibacron blue F3GA and alkali blue 6B immobilized
      poly(hydroxyethyl methacrylate) [PHEMA] cryogel discs were prepared. The cryogel
      discs were characterised by swelling tests, elemental analysis and scanning
      electron microscopy. Each cryogel disc was used for lysozyme adsorption from
      aqueous solutions. Maximum adsorption capacities were 103.3 and 106.7 mg/g for
      cibacron blue F3GA and alkali blue 6B immobilized cryogel discs, respectively.
      Equilibrium lysozyme concentration, pH, ionic strength and temperature were the
      factors of which effect on lysozyme adsorption was investigated. Reusability of
      the cryogel discs was tested and less than 5% decrease in adsorption capacity was
      reported. In the last stage of this work, the cryogel discs were used for
      lysozyme purification from chicken egg white. Molecular weight and purity of the
      eluted lysozyme from cryogel discs were controlled by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. In conclusion, cibacron blue F3GA and alkali
      blue 6B immobilized cryogel discs present a cheap and fast way for purification
      of lysozyme with a high purity.

PMID- 25561056
TI  - High enantioselective Novozym 435-catalyzed esterification of (R,S)-flurbiprofen
      monitored with a chiral stationary phase.
AB  - Lipases form Candida rugosa and Candida antarctica were tested for their
      application in the enzymatic kinetic resolution of (R,S)-flurbiprofen by
      enantioselective esterification. Successful chromatographic separation with well
      resolved peaks of (R)- and (S)-flurbiprofen and their esters was achieved in one
      run on chiral stationary phases by high-performance liquid chromatography (HPLC).
      In this study screening of enzymes was performed, and Novozym 435 was selected as
      an optimal catalyst for obtaining products with high enantiopurity. Additionally,
      the influence of organic solvents (dichloromethane, dichloroethane,
      dichloropropane, and methyl tert-butyl ether), primary alcohols (methanol,
      ethanol, n-propanol, and n-butanol), reaction time, and temperature on the
      enantiomeric ratio and conversion was tested. The high values of enantiomeric
      ratio (E in the range of 51.3-90.5) of the esterification of (R,S)-flurbiprofen
      were obtained for all tested alcohols using Novozym 435, which have a great
      significance in the field of biotechnological synthesis of drugs. The optimal
      temperature range for the performed reactions was from 37 to 45  degrees C. As a
      result of the optimization, (R)-flurbiprofen methyl ester was obtained with a
      high optical purity, eep = 96.3 %, after 96 h of incubation. The enantiomeric
      ratio of the reaction was E = 90.5 and conversion was C = 35.7 %.

PMID- 25561057
TI  - Vertical profiles of community abundance and diversity of anaerobic
      methanotrophic archaea (ANME) and bacteria in a simple waste landfill in north
      China.
AB  - Anaerobic methane oxidation (AMO) is considered to be an important sink of CH4 in
      habitats as marine sediments. But, few studies focused on AMO in landfills which
      may be an important sink of CH4 derived from waste fermentation. To show evidence
      of AMO and to uncover function anaerobic methanotroph (ANME) community in
      landfill, different age waste samples were collected in Jinqianpu landfill
      located in north China. Through high-throughput sequencing, Methanomicrobiales
      and Methanosarcinales archaea associated with ANME and reverse methanogenic
      archaea of Methanosarcina and Methanobacterium were detected. Sulfate-reducing
      bacteria (SRB) (Desulfobulbus and Desulfococcus) which could couple with ANME
      conducting AMO were also found. But, the community structure of ANME had no
      significant difference with depths. From the results of investigation, we can
      come to a conclusion that sulfate-dependent anaerobic methane oxidation (SR-DAMO)
      would be the dominant AMO process in the landfill, while iron-dependent anaerobic
      methane oxidation (M/IR-DAMO) process was weak though concentration of ferric
      iron was large in the landfill. Denitrification-dependent anaerobic methane
      oxidation (NR-DAMO) was negative because of lack of nitrate and relevant function
      microorganisms in the landfill. Results also indicate that CH4 mitigation would
      have higher potential by increasing electron acceptor contents and promoting the
      growth of relevant function microorganisms. 

PMID- 25561058
TI  - Calcium mobilization in salicylic acid-induced Salvia miltiorrhiza cell cultures
      and its effect on the accumulation of rosmarinic acid.
AB  - Ca(2+) serves as a second messenger in plant responses to different signals, and
      salicylic acid (SA) has been recognized as a signal mediating plant responses to
      many stresses. We recently found that SA treatment led to the cytoplasmic
      acidification of Salvia miltiorrhiza cells and alkalinization of extracellular
      medium. Here, we demonstrate that SA can rapidly induce Ca(2+) mobilization in
      protoplasts, but the induction can be blocked with a channel blocker of either
      plasma or organellar membranes. Following SA, A 23187, or 10 mmol/L Ca(2+)
      treatment, rosmarinic acid (RA) accumulation reached the highest level at 16 h,
      whereas the peak was found at 10 h if plasma membrane channel blockers were used.
      By contrast, the highest accumulation of RA occurred at 16 h when organellar
      channels were blocked, exhibiting the same tendency with SA-induced cells. In
      agreement with these observations, both phenylalanine ammonia-lyase (PAL)
      activity and its gene expression detected by real-time PCR also showed the same
      patterns. These results indicate that SA treatment firstly results in calcium
      release from internal stores, which in turn leads to PAL activity increase, RA
      accumulation, and a large amount of Ca(2+) influx from apoplast after 10 h of SA
      induction.

PMID- 25561059
TI  - Mechanisms for solubilization of various insoluble phosphates and activation of
      immobilized phosphates in different soils by an efficient and salinity-tolerant
      Aspergillus niger strain An2.
AB  - Mechanisms for solubilization of different types of phosphates and activation of
      immobilized phosphates in different types of soils by an efficient fungal strain
      An2 were explored and evaluated in this study. An2 was isolated from a Chinese
      cabbage rhizosphere soil and identified as Aspergillus niger. It could fast
      release up to 1722, 2066, and 2356 mg L(-1) of soluble phosphorus (P) from 1 %
      Ca3(PO4)2, Mg3(PO4)2, and AlPO4 (Ca-P, Mg-P, and Al-P) and 215 and 179 mg L(-1)
      from 0.5 % FePO4 and rock phosphate (Fe-P and RP), respectively. HPLC assay
      demonstrated that An2 mainly secreted oxalic acid to solubilize Ca-P, Mg-P, Al-P,
      and Fe-P whereas secreted tartaric acid to solubilize RP. Furthermore, An2 could
      tolerate salinity up to 4 % NaCl without impairing its phosphate-solubilizing
      ability. The simulation experiments validated that An2 was able to effectively
      activate immobilized phosphates in general calcareous, acidic, as well as saline
      alkali soils with high total P content. This study shows new insights into the
      mechanisms for microbial solubilization of different types of phosphates and
      supports the future application of strain An2 in different types of soils to
      effectively activate P for plants.

PMID- 25561060
TI  - Production of fumaric acid from L-malic acid by solvent engineering using a
      recombinant thermostable fumarase from Thermus thermophilus HB8.
AB  - Currently, fumaric acid is produced by catalytic isomerization of maleic acid in
      aqueous solutions at low pH. Being petroleum based, requiring catalyst, and
      producing vast amounts of by-products and wastewater, the production of fumaric
      acid from renewable resources by a "green" process is increasingly attractive. In
      an aqueous solution, the reaction equilibrium constant of the fumarase-mediated
      conversion of L-malic acid to fumaric acid is 1:4.2 (fumaric acid to L-malic
      acid). To shift the reaction equilibrium to fumaric acid, solvent engineering was
      carried out by varying hydrophilic solvents and their concentrations. Generally,
      organic solvents may denature fumarase. Therefore, fumarase from Thermus
      thermophilus was employed to overcome this problem. Ethylene glycol was found
      more suitable than other solvents. This fumarase was shown to be more stable in
      50% than in 70% ethylene glycol. Therefore, a preparation was carried out in 50%
      ethylene glycol. Under this condition, 54.7% conversion was observed using
      fumarase for transforming 1 mmol L-malic acid. After precipitation by adapting
      the pH, and washing to remove residual solvent and substrate, 27% total yield was
      obtained with 99% purity. The results demonstrated that the alternative green
      route to produce bio-based fumaric acid via L-malic acid is feasible and viable.

PMID- 25561061
TI  - Genomic diversity of Saccharomyces cerevisiae yeasts associated with alcoholic
      fermentation of bacanora produced by artisanal methods.
AB  - Bacanora is a spirituous beverage elaborated with Agave angustifolia Haw in an
      artisanal process. Natural fermentation is mostly performed with native yeasts
      and bacteria. In this study, 228 strains of yeast like Saccharomyces were
      isolated from the natural alcoholic fermentation on the production of bacanora.
      Restriction analysis of the amplified region ITS1-5.8S-ITS2 of the ribosomal DNA
      genes (RFLPr) were used to confirm the genus, and 182 strains were identified as
      Saccharomyces cerevisiae. These strains displayed high genomic variability in
      their chromosomes profiles by karyotyping. Electrophoretic profiles of the
      strains evaluated showed a large number of chromosomes the size of which ranged
      between 225 and 2200 kpb approximately.

PMID- 25561064
TI  - Letter to the editor regarding paper "Automatic computation of left ventricular
      volume changes over a cardiac cycle from echocardiography images by nonlinear
      dimensionality reduction".

PMID- 25561063
TI  - Hospital at night: an organizational design that provides safer care at night.
AB  - The reduction in the working hours of doctors represents a challenge to the
      delivery of medical care to acutely sick patients 24 hours a day. Increasing the
      number of doctors to support multiple specialty rosters is not the solution for
      economic or organizational reasons. This paper outlines an alternative,
      economically viable multidisciplinary solution that has been shown to improve
      patient outcomes and provides organizational consistency. The change requires
      strong clinical leadership, with organizational commitment to both cultural and
      structural change. Careful attention to ensuring the teams possess the
      appropriate competencies, implementing a reliable process to identify the sickest
      patients and escalate their care, and structuring rotas efficiently are essential
      features of success. 

PMID- 25561065
TI  - "Evaluation of a very low-cost and simple teleradiology technique".
AB  - This paper describes and analyzes a proposed solution of fundamental limitative
      factor of teleradiology to overcome the teleradiology usages problems in
      underdeveloped and developing countries. The goal is to achieve a very simple and
      cost-efficient way to take advantage of teleradiology in anywhere even in remote
      and rural areas. To meet the goal of this study, the following methodology which
      is consists of two main procedures was done: (1) Using a digital camera in order
      to provide a digital image from radiographs. (2) Using an image compression tool
      in order to compress digital images. The results showed that there is no
      significant difference between digital images (non-compress and compress images)
      and radiographic films. Also, there was a logic relationship between the
      diagnostic quality and diagnostic accuracy. Since the maximum percent of
      diagnostic accuracy can be seen among "Good" quality images and the minimum to
      was related "Poor". The results of our study indicate that a digital camera could
      be utilized to capture digital images from radiographic films of chest x-ray. To
      reduce the size of digital images, a lossy compression technique could be applied
      at compression percent of 50 or less without any significant differences. The
      compressed images can be sent easily by email to other places for consultation
      and also they can be stored with a smaller size. 

PMID- 25561062
TI  - Identification of novel vascular projections with cellular trafficking abilities
      on the microvasculature of pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a nearly lethal neoplasm. It is a
      remarkably stroma-rich, vascular-poor and hypo-perfused tumour, which prevents
      efficient drug delivery. Paradoxically, the neoplastic cells have robust glucose
      uptake, suggesting that the microvasculature has adopted an alternative method
      for nutrient uptake and cellular trafficking. Using adapted thick tumour section
      immunostaining and three-dimensional (3D) construction imaging in human tissue
      samples, we identified an undiscovered feature of the mature microvasculature in
      advanced PDAC tumours; long, hair-like projections on the basal surface of
      microvessels that we refer to as 'basal microvilli'. Functionally, these basal
      microvilli have an actin-rich cytoskeleton and endocytic and exocytic properties,
      and contain glucose transporter-1 (GLUT-1)-positive vesicles. Clinically, as
      demonstrated by PET-CT, the tumour microvasculature with the longest and most
      abundant basal microvilli correlated with high glucose uptake of the PDAC tumour
      itself. In addition, these basal microvilli were found in regions of the tumour
      with low GLUT-1 expression, suggesting that their presence could be dependent
      upon the glucose concentration in the tumour milieu. Similar microvasculature
      features were also observed in a K-Ras-driven model of murine PDAC. Altogether,
      these basal microvilli mark a novel pathological feature of PDAC
      microvasculature. Because basal microvilli are pathological features with endo-
      and exocytic properties, they may provide a non-conventional method for cellular
      trafficking in PDAC tumours.

PMID- 25561066
TI  - An Artificial Immune System-Based Support Vector Machine Approach for Classifying
      Ultrasound Breast Tumor Images.
AB  - A rapid and highly accurate diagnostic tool for distinguishing benign tumors from
      malignant ones is required owing to the high incidence of breast cancer. Although
      various computer-aided diagnosis (CAD) systems have been developed to interpret
      ultrasound images of breast tumors, feature selection and the setting of
      parameters are still essential to classification accuracy and the minimization of
      computational complexity. This work develops a highly accurate CAD system that is
      based on a support vector machine (SVM) and the artificial immune system (AIS)
      algorithm for evaluating breast tumors. Experiments demonstrate that the accuracy
      of the proposed CAD system for classifying breast tumors is 96.67%. The
      sensitivity, specificity, PPV, and NPV of the proposed CAD system are 96.67,
      96.67, 95.60, and 97.48%, respectively. The receiver operator characteristic
      (ROC) area index A z is 0.9827. Hence, the proposed CAD system can reduce the
      number of biopsies and yield useful results that assist physicians in diagnosing
      breast tumors.

PMID- 25561067
TI  - Computer-Aided Methodology for Syndromic Strabismus Diagnosis.
AB  - Strabismus is a pathology that affects approximately 4 % of the population,
      causing aesthetic problems reversible at any age and irreversible sensory
      alterations that modify the vision mechanism. The Hirschberg test is one type of
      examination for detecting this pathology. Computer-aided detection/diagnosis is
      being used with relative success to aid health professionals. Nevertheless, the
      routine use of high-tech devices for aiding ophthalmological diagnosis and
      therapy is not a reality within the subspecialty of strabismus. Thus, this work
      presents a methodology to aid in diagnosis of syndromic strabismus through
      digital imaging. Two hundred images belonging to 40 patients previously diagnosed
      by an specialist were tested. The method was demonstrated to be 88 % accurate in
      esotropias identification (ET), 100 % for exotropias (XT), 80.33 % for
      hypertropias (HT), and 83.33 % for hypotropias (HoT). The overall average error
      was 5.6Delta and 3.83Delta for horizontal and vertical deviations, respectively,
      against the measures presented by the specialist. 

PMID- 25561068
TI  - Using Standardized Lexicons for Report Template Validation with LexMap, a Web
      based Application.
AB  - An enormous amount of data exists in unstructured diagnostic and interventional
      radiology reports. Free text or non-standardized terminologies limit the ability
      to parse, extract, and analyze these report data elements. Medical lexicons and
      ontologies contain standardized terms for relevant concepts including disease
      entities, radiographic technique, and findings. The use of standardized terms
      offers the potential to improve reporting consistency and facilitate computer
      analysis. The purpose of this project was to implement an interface to aid in the
      creation of standards-compliant reporting templates for use in interventional
      radiology. Non-standardized procedure report text was analyzed and referenced to
      RadLex, SNOMED-CT, and LOINC. Using JavaScript, a web application was developed
      which determined whether exact terms or synonyms in reports existed within these
      three reference resources. The NCBO BioPortal Annotator web service was used to
      map terms, and output from this application was used to create an interactive
      annotated version of the original report. The application was successfully used
      to analyze and modify five distinct reports for the Society of Interventional
      Radiology's standardized reporting project. 

PMID- 25561069
TI  - Evaluation of an Automated Information Extraction Tool for Imaging Data Elements
      to Populate a Breast Cancer Screening Registry.
AB  - Breast cancer screening is central to early breast cancer detection. Identifying
      and monitoring process measures for screening is a focus of the National Cancer
      Institute's Population-based Research Optimizing Screening through Personalized
      Regimens (PROSPR) initiative, which requires participating centers to report
      structured data across the cancer screening continuum. We evaluate the accuracy
      of automated information extraction of imaging findings from radiology reports,
      which are available as unstructured text. We present prevalence estimates of
      imaging findings for breast imaging received by women who obtained care in a
      primary care network participating in PROSPR (n = 139,953 radiology reports) and
      compared automatically extracted data elements to a "gold standard" based on
      manual review for a validation sample of 941 randomly selected radiology reports,
      including mammograms, digital breast tomosynthesis, ultrasound, and magnetic
      resonance imaging (MRI). The prevalence of imaging findings vary by data element
      and modality (e.g., suspicious calcification noted in 2.6% of screening
      mammograms, 12.1% of diagnostic mammograms, and 9.4% of tomosynthesis exams). In
      the validation sample, the accuracy of identifying imaging findings, including
      suspicious calcifications, masses, and architectural distortion (on mammogram and
      tomosynthesis); masses, cysts, non-mass enhancement, and enhancing foci (on MRI);
      and masses and cysts (on ultrasound), range from 0.8 to1.0 for recall, precision,
      and F-measure. Information extraction tools can be used for accurate
      documentation of imaging findings as structured data elements from text reports
      for a variety of breast imaging modalities. These data can be used to populate
      screening registries to help elucidate more effective breast cancer screening
      processes.

PMID- 25561071
TI  - The Enhanced Workflow and Efficiency of the Wireless Local Area Network (WLAN)
      Based Direct Digital Radiography (DDR) Portable Radiography.
AB  - With the implementation of the PACS in the hospital, there is an increasing
      demand from the clinicians for immediate access and display of radiological
      images. Recently, our hospital has installed the first wireless local area
      network (WLAN)-based direct digital radiography (DDR) portable radiography
      system. The DDR portable radiography system allows wireless retrieval of modality
      worklist and wireless transmission of portable X-ray image on the console to the
      Picture Archiving and Communication System (PACS), via WLAN connection of
      wireless fidelity (Wi-Fi). The aim of this study was to analyze the workflow and
      performance between the WLAN-based DDR portable radiography system and the old
      practice using conventional portable X-ray machine with computed radiography (CR)
      system. A total of 190 portable chest X-ray examinations were evaluated and
      timed, using the conventional portable X-ray machine with CR from March to April
      of 2012 and using the new DDR portable radiography system on December of 2012 (n
      = 97 for old system and n = 93 for DDR portable system). The time interval of
      image becoming available to the PACS using the WLAN-based DDR portable
      radiography system was significantly shorter than that of the old practice using
      the conventional portable X-ray machine with CR (6.8 +/- 2.6 min for DDR portable
      system; 23 +/- 10.2 min for old system; p < 0.0001), with the efficiency improved
      by 70 %. The implementation of the WLAN-based DDR portable radiography system can
      enhance the workflow of portable radiography by reduction of procedural steps.

PMID- 25561070
TI  - Ruler Based Automatic C-Arm Image Stitching Without Overlapping Constraint.
AB  - In this paper, we propose a new method for stitching multiple fluoroscopic images
      taken by a C-arm instrument. We employ an X-ray radiolucent ruler with numbered
      graduations while acquiring the images, and the image stitching is based on
      detecting and matching ruler parts in the images to the corresponding parts of a
      virtual ruler. To achieve this goal, we first detect the regular spaced
      graduations on the ruler and the numbers. After graduation labeling, for each
      image, we have the location and the associated number for every graduation on the
      ruler. Then, we initialize the panoramic X-ray image with the virtual ruler, and
      we "paste" each image by aligning the detected ruler part on the original image,
      to the corresponding part of the virtual ruler on the panoramic image. Our method
      is based on ruler matching but without the requirement of matching similar
      feature points in pairwise images, and thus, we do not necessarily require
      overlap between the images. We tested our method on eight different datasets of X
      ray images, including long bones and a complete spine. Qualitative and
      quantitative experiments show that our method achieves good results.

PMID- 25561072
TI  - Study of Radiologic Technologists' Perceptions of Picture Archiving and
      Communication System (PACS) Competence and Educational Issues in Western
      Australia.
AB  - Although the implementation of picture archiving and communication system (PACS)
      could increase productivity of radiology departments, this depends on factors
      such as the PACS competence of radiologic technologists (RTs). The purpose of
      this study was to investigate the RTs' perceptions of PACS competence and
      educational issues in Western Australia (WA). A hardcopy questionnaire was
      distributed to WA RTs for obtaining their perceptions of PACS competence and
      educational issues. Descriptive (percentage of frequency, mean and standard
      deviation) and inferential statistics (t test and analysis of variance) were used
      to analyze the responses of the multiple choice and five-point scale questions
      from the returned questionnaires. The questionnaire response rate was 57.7% (173
      out of 300). The mean values of all PACS competence questions except questions 2e
      g are in the range of 3.9-4.9, i.e., around competent to very competent.
      Participants indicated they received adequate PACS training (mean 3.8).
      Statistically significant variables influencing RTs' perceptions of their PACS
      competence and educational issues including the age (p < 0.01), gender (p <
      0.05), years of practice (p < 0.005-0.05), primary duty (p < 0.05), medical
      imaging qualification (p < 0.001), general computer skills (p < 0.001), and type
      of PACS education received (p < 0.001-0.05). The WA RTs indicated that they were
      competent in using the modality workstation, PACS and radiology information
      system, and received adequate training. However, future PACS education programs
      should be tailored to different RTs' groups. For example, multiple training
      modules might be necessary to support the PACS competence development of older
      RTs and those with lower general computer literacy.

PMID- 25561073
TI  - Staining correction in digital pathology by utilizing a dye amount table.
AB  - The stained colors of the tissue components are popularly used as features for
      image analysis. However, variations in the staining condition of the histology
      slides prompt variations to the color distribution of the stained tissue samples
      which could impact the accuracy of the analysis. In this paper, we present a
      method to correct the staining condition of a histology image. In the method, a
      look-up table (LUT) based on the dye amounts absorbed by the sample is built. The
      LUT can be built when either (i) the source and reference staining conditions are
      specified or (ii) when the user simply wants to recreate his/her preferred
      staining condition without specifying any reference slide. The effectiveness of
      the present method was evaluated in two aspects: (i) CIELAB color difference of
      nuclei, cytoplasm, and red blood cells, between the ten different slides of liver
      tissue, and (ii) classification of the different tissue components. Application
      of the present staining correction method reduced the color difference between
      the slides by an average factor of 9.8 and the classification performance of a
      linear discriminant classifier improved by 16.5% on the average. Results of the
      paired t test statistical analysis further showed that the reduction in the
      CIELAB color difference between the slides and the improvement in the
      classifier's performance when staining correction was implemented is significant
      at p < 0.001.

PMID- 25561074
TI  - Low sensitivity of F-wave in the electrodiagnosis of carpal tunnel syndrome.
AB  - OBJECTIVE: Previous studies showed "F-wave inversion" (F-INV) as a sensitive
      method in the electrodiagnosis of early stage of carpal tunnel syndrome (CTS).
      This study aimed at evaluating the sensitivity and specificity of F-wave and
      nerve conduction velocity (NCV) testing in CTS. METHODS: We consecutively
      enrolled 244 cases and 108 controls. F-waves analysis included: Fwave minimum and
      mean latencies, F-wave persistence and chronodispersion, mean-F/CMAP amplitude
      ratio, F-INV. Specificity and sensitivity of F-waves parameters were calculated
      in the whole sample of CTS patients and by grouping the patients according to CTS
      severity. Multivariate logistic regression was also performed using F-INV as a
      dependent variable. RESULTS: In the whole sample the sensitivity of F-mean-INV
      and of median-ulnar NCV comparative testing was 50.8% and 93.7%, respectively. F
      INV sensitivity dropped to 8% in CTS early stage. F-INV could be predicted only
      by distal motor latency of the median nerve. The sensitivity of all F-wave
      parameters increased only in the most severe stages of CTS. CONCLUSIONS: This
      study does not confirm the electrodiagnostic usefulness of F-INV in early stage
      of CTS. All F-wave parameters, including F-INV, are much less sensitive than
      conventional NCV in CTS electrodiagnosis. F-wave does not add further useful
      information specifically related to CTS.

PMID- 25561075
TI  - Immediate increases in quadriceps corticomotor excitability during an
      electromyography biofeedback intervention.
AB  - The purpose of the study was to determine the effects of EMG-BF on vastus
      lateralis corticomotor excitability, measured via motor evoked potential (MEP)
      amplitudes elicited using Transcranial Magnetic Stimulation (TMS) during a
      maximal voluntary isometric contraction (MVIC). We also determined the effect of
      EMG-BF on isometric knee extensor strength. Fifteen healthy participants
      volunteered for this crossover study with two sessions held one-week apart.
      Participants were randomly assigned to condition order, during which five
      intervention MVICs were performed with or without EMG-BF. MEP amplitudes were
      collected with TMS during five knee extension contractions (5% of MVIC) at
      baseline and again during intervention MVICs within each session. During the
      control condition, participants were instructed to perform the same number of
      MVICs without any EMG-BF. Percent change scores were used to calculate the change
      in peak-to-peak MEP amplitudes that occurred during EMG-BF and Control MVICs
      compared to the baseline MEPs. Peak knee extension torque was recorded during
      MVICs prior to TMS for each condition. EMG-BF produced significantly increased
      MEP change scores and significantly greater torque than the control condition.
      The results of the current study suggest that EMG-BF may be a viable clinical
      method for targeting corticomotor excitability. 

PMID- 25561076
TI  - Exposure to traumatic perinatal experiences and posttraumatic stress symptoms in
      midwives: prevalence and association with burnout.
AB  - BACKGROUND: Midwives provide care in a context where life threatening or
      stressful events can occur. Little is known about their experiences of traumatic
      events or the implications for psychological health of this workforce.
      OBJECTIVES: To investigate midwives' experiences of traumatic perinatal events
      encountered whilst providing care to women, and to consider potential
      implications. DESIGN: A national postal survey of UK midwives was conducted.
      PARTICIPANTS: 421 midwives with experience of a perinatal event involving a
      perceived risk to the mother or baby which elicited feelings of fear,
      helplessness or horror (in the midwife) completed scales assessing posttraumatic
      stress symptoms, worldview beliefs and burnout. RESULTS: 33% of midwives within
      this sample were experiencing symptoms commensurate with clinical posttraumatic
      stress disorder. Empathy and previous trauma exposure (personal and whilst
      providing care to women) were associated with more severe posttraumatic stress
      responses. However, predictive utility was limited, indicating a need to consider
      additional aspects increasing vulnerability. Symptoms of posttraumatic stress
      were associated with negative worldview beliefs and two domains of burnout.
      CONCLUSIONS: Midwives may experience aspects of their work as traumatic and, as a
      consequence, experience posttraumatic stress symptomatology at clinical levels.
      This holds important implications for both midwives' personal and professional
      wellbeing and the wellbeing of the workforce, in addition to other maternity
      professionals with similar roles and responsibilities. Organisational strategies
      are required to prepare midwives for such exposure, support midwives following
      traumatic perinatal events and provide effective intervention for those with
      significant symptoms.

PMID- 25561078
TI  - Antibiotic prophylaxis for preventing infectious complications in orthognathic
      surgery.
AB  - BACKGROUND: Orthognathic surgery (OS) is a term that refers to many elective
      surgical techniques to correct facial deformity; the associated malocclusion and
      functional disorders related to the stomatognathic system. Whilst such surgery is
      classed as "clean-contaminated", the usefulness of and the most appropriate
      regimen for antibiotic prophylaxis in these patients are still debated.
      OBJECTIVES: To assess the effects of antibiotic prophylaxis for preventing
      surgical site infection (SSI) in people undergoing orthognathic surgery. SEARCH
      METHODS: In June 2014, we searched the Cochrane Wounds Group Specialised
      Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed
      Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched Google Scholar and
      performed manual searches in journals relevant to the topic, conference
      proceedings and lists of references of potentially included articles. We did not
      restrict the search and study selection with respect to language, date of
      publication or study setting. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) involving people undergoing orthognathic surgery
      comparing one regimen of antibiotic prophylaxis with any other regimen or
      placebo. The primary outcome was SSI, and secondary outcomes were systemic
      infections, adverse events, duration of hospital stay and health-related quality
      of life. Two review authors screened articles independently. DATA COLLECTION AND
      ANALYSIS: Data were abstracted independently by two review authors, and agreement
      was checked. Risk of bias was assessed using the Cochrane risk of bias tool.
      Antibiotic regimens were classified as preoperative (one dose before surgery),
      short-term (before or during surgery and/or during the same day of surgery) and
      long-term (before or during surgery and longer than one day after surgery)
      antibiotic prophylaxis. Random-effects meta-analyses using inverse variance
      methods were undertaken when possible. We report risk ratios (RRs) and their
      corresponding 95% confidence intervals (CIs). MAIN RESULTS: A total of 11 trials
      were included in this review. Most of the studies had an unclear risk of bias
      prompting us to downgrade the quality of evidence for our outcomes. Seven of
      these trials provided evidence for the main comparison and the primary outcome
      and these were pooled. Overall, long-term antibiotic prophylaxis probably reduces
      the risk of SSI (plausible effects range between a 76% to a 0.26% relative
      reduction in SSI with long-term antibiotic prophylaxis) (472 participants; RR
      0.42, 95% CI 0.24 to 0.74; moderate-quality evidence). There is uncertainty
      surrounding the relative effects of short-term antibiotics compared with a single
      dose (220 participants; RR 0.34, 95% CI 0.09 to 1.22; low-quality evidence). No
      reports described adverse effects associated with the drugs in those trials that
      reported in this outcome. None of these trials assessed or reported data
      regarding other outcomes, and information was insufficient to show whether a
      specific antibiotic is better than another. AUTHORS' CONCLUSIONS: For people
      undergoing orthognathic surgery, long term antibiotic prophylaxis decreases the
      risk of SSI compared with short-term antibiotic prophylaxis and the is
      uncertainty of whether short-term antibiotic prophylaxis decreases SSi risk
      relative to a single pre-operative dose of prophylactic antibiotics.

PMID- 25561077
TI  - Papuloerythroderma of Ofuji associated with CD3,(+) CD4,(+) and CD8(-) cutaneous
      T-cell lymphoma and monoclonal gammopathy of undetermined significance.

PMID- 25561079
TI  - Therapeutic play intervention on children's perioperative anxiety, negative
      emotional manifestation and postoperative pain: a randomized controlled trial.
AB  - AIM: To examine if therapeutic play intervention could reduce perioperative
      anxiety, negative emotional manifestation and postoperative pain in children
      undergoing inpatient elective surgery. BACKGROUND: Children undergoing surgery
      commonly experience anxiety and postoperative pain and exhibit negative emotional
      manifestations. Previous studies have shown inconsistent conclusions about the
      influence of therapeutic play on children's perioperative anxiety, negative
      emotional manifestation and postoperative pain. DESIGN: A randomized controlled
      trial was used. METHODS: Suitable children were recruited from November 2011
      August 2013. They were randomized to receive either routine care (control group,
      n = 47) or a 1-hour therapeutic play intervention (experimental group, n = 48).
      Children's state anxiety, negative emotional manifestations and postoperative
      pain were measured at baseline, on the day of surgery and around 24 hours after
      surgery. Repeated measures analysis of covariance (ancova) and univariate ancova
      adjusting for all possible confounding factors were used in the data analysis.
      RESULTS: The time effect of state anxiety was significant, but no group and
      interaction (group x time) effects between the control and experimental groups
      were found. Compared with the control group, children in the experimental group
      demonstrated significantly lower scores of negative emotional manifestations
      prior to anaesthesia induction and postoperative pain. CONCLUSIONS: Therapeutic
      play intervention is effective in reducing negative emotional manifestations
      before anaesthesia induction and in reducing postoperative pain in children
      undergoing inpatient elective surgery. These results suggest that it is useful to
      give children with therapeutic play intervention prior to inpatient elective
      surgery.

PMID- 25561080
TI  - Acute kidney injury in 2014: a step towards understanding mechanisms of renal
      repair.
AB  - In 2014, key articles in the field of acute kidney injury highlighted the
      importance of tubular homeostasis in renal regeneration. Cell cycle regulators,
      inflammatory signals and progenitors were identified as important factors that
      mediate the balance between inflammation and tubular regeneration necessary for
      renal repair.

PMID- 25561082
TI  - Long-term in vitro cultivation of Borrelia miyamotoi.
AB  - Borrelia are fastidious bacteria some of which are difficult to grow in vitro.
      Here, we report a method for successful continuous in vitro cultivation of the
      emerging pathogen Borrelia miyamotoi. The type and quantity of serum as well as
      the atmosphere were critical for successful in vitro cultivation. Optimal growth
      was achieved using 50% pooled human serum and an atmosphere of 6% CO2. 

PMID- 25561084
TI  - Treating the untreatable in art and heritage materials: ultrafast laser cleaning
      of "cloth-of-gold".
AB  - Laser cleaning provides art and heritage conservators with an alternative means
      to restore objects when traditional chemical and mechanical methods are not
      viable. However, long (>nanosecond) laser pulses can cause unwanted damage from
      photothermal processes and provide limited control over ablation depth.
      Ultrashort (<picosecond) pulse lasers are emerging as a more appropriate tool for
      cleaning historic artifacts because of their unique ability to avoid heat- and
      shock-wave generation, thus minimizing collateral damage of the underlayers, and
      to remove material with near-nanometer precision. Here we demonstrate the
      effectiveness of ultrashort pulses by cleaning 19th century military gold braid
      without any detrimental effects on the gold foil or the underlying silk thread
      structure. The results are compared with nanosecond-pulse laser treatment that
      damages the surface structure. By introducing in situ feedback control of the
      laser ablation via laser-induced breakdown spectroscopy (LIBS) monitoring of the
      ablated plume, we are able to halt the cleaning process just as the contaminant
      layer is completely removed. This technique allows ultrafast laser ablation to
      extend the armory of conservation treatments, enabling restoration of a range of
      complex and fragile heritage objects previously untreatable by conventional
      means. 

PMID- 25561081
TI  - Cardiac imaging in patients with chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) carry a high cardiovascular risk. In
      this patient group, cardiac structure and function are frequently abnormal and
      74% of patients with CKD stage 5 have left ventricular hypertrophy (LVH) at the
      initiation of renal replacement therapy. Cardiac changes, such as LVH and
      impaired left ventricular systolic function, have been associated with an
      unfavourable prognosis. Despite the prevalence of underlying cardiac
      abnormalities, symptoms may not manifest in many patients. Fortunately, a range
      of available and emerging cardiac imaging tools may assist with diagnosing and
      stratifying the risk and severity of heart disease in patients with CKD.
      Moreover, many of these techniques provide a better understanding of the
      pathophysiology of cardiac abnormalities in patients with renal disease.
      Knowledge of the currently available cardiac imaging modalities might help
      nephrologists to choose the most appropriate investigative tool based on
      individual patient circumstances. This Review describes established and emerging
      cardiac imaging modalities in this context, and compares their use in CKD
      patients with their use in the general population. 

PMID- 25561083
TI  - A map of community-based obesity prevention initiatives in Australia following
      obesity funding 2009-2013.
AB  - OBJECTIVE: Obesity is the single biggest public health threat to developed and
      developing economies. In concert with healthy public policy, multi-strategy,
      multi-level community-based initiatives appear promising in preventing obesity,
      with several countries trialling this approach. In Australia, multiple levels of
      government have funded and facilitated a range of community-based obesity
      prevention initiatives (CBI), heterogeneous in their funding, timing, target
      audience and structure. This paper aims to present a central repository of CBI
      operating in Australia during 2013, to facilitate knowledge exchange and shared
      opportunities for learning, and to guide professional development towards best
      practice for CBI practitioners. METHODS: A comprehensive search of government,
      non-government and community websites was undertaken to identify CBI in Australia
      in 2013. This was supplemented with data drawn from available reports, personal
      communication and key informant interviews. The data was translated into an
      interactive map for use by preventive health practitioners and other parties.
      RESULTS: We identified 259 CBI; with the majority (84%) having a dual focus on
      physical activity and healthy eating. Few initiatives, (n=37) adopted a four
      pronged multi-strategy approach implementing policy, built environment, social
      marketing and/or partnership building. CONCLUSION: This comprehensive overview of
      Australian CBI has the potential to facilitate engagement and collaboration
      through knowledge exchange and information sharing amongst CBI practitioners,
      funders, communities and researchers. IMPLICATIONS: An enhanced understanding of
      current practice highlights areas of strengths and opportunities for improvement
      to maximise the impact of obesity prevention initiatives.

PMID- 25561085
TI  - Methionine deficiency leads to hepatic fat accretion via impairment of fatty acid
      import by carnitine palmitoyltransferase I.
AB  - 1. To clarify the underlying mechanism of hepatic fat accretion due to methionine
      (Met) deficiency in broiler chickens, the present study investigated the effect
      of Met deficiency on the hepatic carnitine palmitoyltransferase (CPT) system,
      which imports fatty acids into mitochondria. 2. Fifteen-d-old male meat-type
      chickens were fed on either a control diet (containing 0.52 g/100 g Met) or a Met
      deficient diet (containing 0.27 g Met/100 g). After a 10-d feeding period, the
      birds were killed by decapitation and their livers excised to determine hepatic
      CPT1 and CPT2 mRNA levels and for the related hepatic fatty acid-supported
      mitochondrial respiration to be measured. 3. Met deficiency decreased body weight
      gain and feed efficiency and increased hepatic lipid content compared to the
      control group. Whereas the hepatic CPT2 mRNA level in the Met-deficient group
      remained unchanged compared to that of the control group, the CPT1 mRNA level was
      decreased in the Met-deficient group and CPT1-dependent hepatic mitochondrial
      respiration was impaired. 4. Our results suggest that the hepatic lipid accretion
      that occurs in response to Met deficiency might be attributable to the impairment
      of CPT1-mediated fatty acid import into mitochondria. 

PMID- 25561086
TI  - Preferential allocation, physio-evolutionary feedbacks, and the stability and
      environmental patterns of mutualism between plants and their root symbionts.
AB  - The common occurrence of mutualistic interactions between plants and root
      symbionts is problematic. As the delivery of benefit to hosts involves costs to
      symbionts, symbionts that provide reduced benefit to their host are expected to
      increase in frequency. Plants have been shown to allocate preferentially to the
      most efficient symbiont and this preferential allocation may stabilize the
      mutualism. I construct a general model of the interactive feedbacks of host
      preferential allocation and the dynamics of root symbiont populations to evaluate
      the stability of nutritional mutualisms. Preferential allocation can promote the
      evolution of mutualism even when the cost to the symbiont is very large.
      Moreover, the physiological plasticity of preferential allocation likely leads to
      coexistence of beneficial and nonbeneficial symbionts. For arbuscular mycorrhizal
      fungi, which facilitate plant uptake of phosphorus (P), the model predicts
      greater P transfer from these fungi per unit carbon invested with decreasing
      concentrations of soil P and with increasing concentrations of atmospheric CO2 ,
      patterns that have been observed in laboratory and field studies. This framework
      connects physiological plasticity in plant allocation to population processes
      that determine mutualism stability and, as such, represents a significant step in
      understanding the stability and environmental patterns in mutualism. 

PMID- 25561087
TI  - A review on airway biomarkers: exposure, effect and susceptibility.
AB  - Current research in pulmonology requires the use of biomarkers to investigate
      airway exposure and diseases, for both diagnostic and prognostic purposes. The
      traditional approach based on invasive approaches (lung lavages and biopsies) can
      now be replaced, at least in part, through the use of non invasively collected
      specimens (sputum and breath), in which biomarkers of exposure, effect and
      susceptibility can be searched. The discovery of specific lung-related proteins,
      which can spill over in blood or excreted in urine, further enhanced the spectrum
      of airway specific biomarkers to be studied. The recent introduction of high
      performance 'omic' technologies - genomics, proteomics and metabolomics, and the
      rate at which biomarker candidates are being discovered, will permit the use of a
      combination of biomarkers for a more precise selection of patient with different
      outcomes and responses to therapies. The aim of this review is to critically
      evaluate the use of airway biomarkers in the context of research and clinical
      practice. 

PMID- 25561088
TI  - Intimate Partner Sexual Violence: A Review of Terms, Definitions, and Prevalence.
AB  - Intimate partner sexual violence (IPSV) is a significant aspect of intimate
      partner violence (IPV). While intimate partners commit one third of sexual
      assaults, IPSV is often overlooked in studies about IPV and in research on sexual
      violence. There are difficulties identifying, defining, and measuring IPSV, and
      research lacks consistency in terminology and measurement. The purpose of this
      article is to review the terms, definitions, and measurements associated with
      IPSV. Academic journals and nonscholarly documents from the United States were
      searched for articles and reports associated with the study of sexual violence
      and IPV. Forty-nine documents met the criteria for inclusion. A four-part
      taxonomy defining IPSV was developed, which included IPSV, intimate partner
      sexual coercion, intimate partner sexual abuse, and intimate partner forced
      sexual activity. The average weighted prevalence rates of these various forms of
      IPSV were calculated across included research studies. However, the measurements
      generally used to assess IPV do not adequately measure IPSV. Future research
      should consist terms to ensure consistent conceptualization and measurement of
      IPSV and to inform practice with survivors. 

PMID- 25561090
TI  - One hundred and twenty-five years of the Annals of Botany. Part 1: the first 50
      years (1887-1936).
AB  - BACKGROUND: The Annals of Botany is a peer-reviewed scientific journal publishing
      papers on a wide range of topics in plant biology. It first appeared in 1887,
      making it the oldest continuously published botanical title. The present article
      gives a historical account of events leading to the founding of the Journal and
      of its development over the first 50 years. SOURCES OF INFORMATION: Much of the
      content is drawn from the Journal's own records and from extensive Minutes,
      financial accounts, personal letters and notes relating to the Annals of Botany
      that were repatriated from University College, University of London in 1999.
      Documents held at the Royal Botanic Gardens, Kew and at the Oxford University
      Press Museum were also consulted. CONTENT: Emphasis is placed on the individuals
      who instigated, edited and managed the Annals of Botany up to 1937, especially
      the nine founding members of the Journal and the background that brought them
      together and motivated them to start the Annals of Botany. A falling out between
      two of the founders in 1899 is highlighted since not only did this threaten the
      Journal's future but also gives much insight into the personalities of those most
      closely involved in the Journal during its formative years. The article also
      examines the way the Journal was funded and how it dealt with its publisher (the
      University of Oxford's Clarendon Press), turned itself into a registered company
      (the Annals of Botany Company) and coped with the travails of the First World
      War, currency inflation and the Great Depression. Plans to re-start the Journal
      as a New Series, beginning in 1937, are discussed in the context of the
      competition the Annals of Botany then faced from younger journals.

PMID- 25561089
TI  - Both high and low HbA1c predict incident heart failure in type 2 diabetes
      mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus is an independent risk factor for heart
      failure development, but the relationship between incident heart failure and
      antecedent glycemia has not been evaluated. METHODS AND RESULTS: The Genetics of
      Diabetes Audit and Research in Tayside Study study holds data for 8683
      individuals with type 2 diabetes mellitus. Dispensed prescribing, hospital
      admission data, and echocardiography reports were linked to extract incident
      heart failure cases from December 1998 to August 2011. All available HbA1c
      measures until heart failure development or end of study were used to model HbA1c
      time-dependently. Individuals were observed from study enrolment until heart
      failure development or end of study. Proportional hazard regression calculated
      heart failure development risk associated with specific HbA1c ranges accounting
      for comorbidities associated with heart failure, including blood pressure, body
      mass index, and coronary artery disease. Seven hundred and one individuals with
      type 2 diabetes mellitus (8%) developed heart failure during follow up (mean 5.5
      years, +/-2.8 years). Time-updated analysis with longitudinal HbA1c showed that
      both HbA1c <6% (hazard ratio =1.60; 95% confidence interval, 1.38-1.86; P value
      <0.0001) and HbA1c >10% (hazard ratio =1.80; 95% confidence interval, 1.60-2.16;
      P value <0.0001) were independently associated with the risk of heart failure.
      CONCLUSIONS: Both high and low HbA1c predicted heart failure development in our
      cohort, forming a U-shaped relationship.

PMID- 25561091
TI  - Cytotoxicity and induction of apoptosis by formamidinodoxorubicins in comparison
      to doxorubicin in human ovarian adenocarcinoma cells.
AB  - BACKGROUND/AIM: In this study we investigated the effect of DOX and five of its
      derivatives containing a formamidine group (NCHNRR) at the 3' position with
      pyrrolidine (DOX-F PYR), piperidine (DOX-F PIP), morpholine (DOX-F MOR), N
      methylpiperazine (DOX-F PAZ) and hexamethyleneimine (DOX-F HEX) ring on SKOV-3
      ovarian cancer cells. We have focused on the anti-proliferative activity and the
      value of apoptosis induced by tested analogues. MATERIALS AND METHODS: The
      following methods were used: spectrophotometric assay with MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide); fluorimetric assays -
      double staining with Hoechst 33258 and propidium iodide (PI), measurement of
      caspase-3 activity; flow cytometry methods - phosphatidylserine (PS)
      externalization using Annexin V-FITC and PI fluorochromes, and TUNEL assay.
      RESULTS: All of the investigated derivatives were considerably more cytotoxic to
      the SKOV-3 cell line than DOX. The predominant type of cell death induced by the
      anthracycline analogues was apoptosis. Necrotic cells represented only a small
      percentage (<5%) of all cells. The number of apoptotic cells was dependent on the
      compound and the incubation time. Moreover, a significant increase in caspase-3
      activity, DNA fragmentation, and morphological changes in ovarian cells were
      observed predominantly in new DOX analogues. CONCLUSIONS: All new formamidine
      derivatives of DOX were effective against ovarian cancer cells. They induced
      mainly the apoptotic pathway of cell death mediated by caspase-3. The most
      promising results were obtained for DOX-F MOR and DOX-F PAZ. The least potent was
      DOX-F HEX.

PMID- 25561092
TI  - Nephroprotective effect of vanillic acid against cisplatin induced nephrotoxicity
      in wistar rats: a biochemical and molecular study.
AB  - Cisplatin is one of the extensively used anticancer drugs against various
      cancers. Dosage dependent nephrotoxicity is the major problem in cisplatin
      chemotherapy. Cisplatin induced nephrotoxicity results in the depletion of renal
      antioxidant defence system. Our present study is aimed to investigate the
      nephroprotective effect of vanilic acid to against cisplatin induced
      nephrotoxicity in male wistar rats. Elevated levels of serum creatinine, blood
      urea nitrogen, serum uric acid and reduced antioxidant status were observed as
      indicatives of nephrotoxicity in cisplatin (7mg/kg bw) alone administered rats.
      Animals which are pre-treated with vanillic acid (50mg/kg and 100mg/kg) restored
      the elevated levels of renal function markers and reduced antioxidant status to
      near normalcy when compared to cisplatin alone treated animals. Cisplatin induced
      lipid peroxidation was markedly reduced by oral administration of vanillic acid
      at a high dose. The findings in the present study suggest that vanillic acid is a
      potential antioxidant that reduce cisplatin nephrotoxicity and can be as a
      combinatorial regimen in cancer chemotherapy. 

PMID- 25561093
TI  - Cardiovascular risk factors in children and adolescents with anxiety disorders
      and their association with disease severity.
AB  - INTRODUCTION: Studies suggest that anxiety is an independent predictor of adverse
      cardiovascular events. However, few studies have investigated the association
      between cardiovascular risk factors (RF) and severity of anxiety disorders (AD)
      in childhood and adolescents. OBJECTIVES: To assess the prevalence of
      cardiovascular RF in children and adolescents with anxiety disorders and their
      association with disease severity. METHOD: Cross-sectional study assessing
      nutritional and anthropometric RF, as well as % body fat (BF), blood pressure
      (BP), physical activity level, anxiety symptoms and severity of the anxiety
      disorder of children and adolescents. RESULTS: A total of 65 children and
      adolescents (8.6 ?} 1.7 years) took part in the study. Excess saturated fatty
      acid intake (52.3%), high body mass index (50.8%), high BP (50.8%) and physical
      inactivity (50.0%) were the most prevalent cardiovascular RF. There was a
      significant association between the severity of the anxiety and the presence of
      >= 6 RF per patient (p=0.026), excess abdominal body fat as assessed by waist
      circumference (p=0.019) and conicity index (p=0,053), and excess % BF (p=0.035).
      Generalized anxiety disorder was significantly associated with high BP (p=0.044).
      CONCLUSION: A high prevalence of cardiovascular RF was found in the present
      sample, and individuals with more severe anxiety had greater cardiovascular risk.
      The characterization of the cardiovascular risk in young populations, especially
      in individuals with AD who are therefore more susceptible to CVD, is crucial for
      the development of lifestyle interventions in these patients.

PMID- 25561094
TI  - [Methylmercury: existing recommendations; methods of analysing and interpreting
      the results; economic evaluation].
AB  - The beneficial effects of fish consumption are well- known. Nevertheless, there
      is worldwide concern regard methylmercury concentrations in fish, which is why
      many countries such as the United States, Australia, New Zealand, Canada and
      numerous European countries have made fish consumption recommendations for their
      populations, particularly vulnerable groups, in order to Mexico methylmercury
      intake. Blood and hair are the best biological samples for measuring
      methylmercury. The most widely-used method to analyse methylmercury is cold vapor
      atomic absorption spectrometry, although there are also direct methods based on
      the thermal decomposition of the sample. In recent years, the number of
      laboratories that measure mercury by inductively coupled plasma mass spectrometry
      has increased. In addition, the different kinds of mercury can be distinguished
      by coupling chromatography methods of separation. Laboratories that analyse
      mercury in biological samples need to participate in external quality control
      programmes. Even if mercury emissions are reduced, mercury may remain in the
      environment for many years, so dietary recommendations are fundamental in order
      to reduce exposure. It is necessary to propose public health measures aimed at
      decreasing mercury exposure and to evaluate the benefits of such measures from
      the economic and social standpoints. 

PMID- 25561095
TI  - [Consensus document on the prevention of exposure to methylmercury in Spain].
AB  - The beneficial effects of fish consumption in both children and adults are well
      known. However, the intake of methylmercury, mainly from contaminated fish and
      shellfish, can have adverse health effects. The study group on the prevention of
      exposure to methylmercury (GEPREM-Hg), made up of representatives from different
      Spanish scientific societies, has prepared a consensus document in a question and
      answer format, containing the group's main conclusions, recommendations and
      proposals. The objective of the document is to provide broader knowledge of
      factors associated with methylmercury exposure, its possible effects on health
      among the Spanish population, methods of analysis, interpretation of the results
      and economic costs, and to then set recommendations for fish and shellfish
      consumption. The group sees the merit of all initiatives aimed at reducing or
      prohibiting the use of mercury as well as the need to be aware of the results of
      contaminant analyses performed on fish and shellfish marketed in Spain. In
      addition, the group believes that biomonitoring systems should be set up in order
      to follow the evolution of methylmercury exposure in children and adults and
      perform studies designed to learn more about the possible health effects of
      concentrations found in the Spanish population, ta king into account the
      lifestyle, eating patterns and the Mediterranean diet. 

PMID- 25561096
TI  - [Are antioxidant supplements effective in reducing delayed onset muscle soreness?
      A systematic review].
AB  - INTRODUCTION: In recent years, antioxidant supplements have become popular to
      counter the effects of free radicals and muscle damage symptoms, including
      delayed onset muscle soreness (DOMS). AIM: To conduct a systematic review in
      different databases to determine the effects of antioxidant supplements on DOMS.
      METHODS: We conducted a search in databases; Cochrane, Pubmed, Scopus and
      SportDiscus and Web of Science (WOS). The words and acronyms used were; Delayed
      onset muscle soreness, exercise induced muscle damage, DOMS, EIMD, antioxidant
      and oxidative stress. RESULTS: 54 articles were identified of which 48 were
      retreived, all in English, 17 related to vitamin C and E, supplements
      polyphenolic correspond to fourteen, eleven other antioxidant supplements and six
      to commercial supplements, all of them used to diminish the DOMS and other
      variables. CONCLUSIONS: Both vitamins and commercial supplements have low
      effectiveness in reducing DOMS, while polyphenols and other antioxidant
      supplements show moderate to good effectiveness in combating DOMS. However, most
      of the studies have effectiveness in reducing other symptoms of muscle damage
      besides helping in the post-exercise recovery.

PMID- 25561097
TI  - [Macronutrients, food intake and body weight; the role of fat].
AB  - INTRODUCTION: "Globesity" is the term that the World Health Organization (WHO)
      employs to define the growth of obesity in the world from the last 40 years which
      started in the developed countries and has been inevitably propagated to the
      developing ones. Governments and international organizations are aware of the
      problem and they are trying to implement measures to fight it. AIM: To analyze
      the current evidence in terms of studies about the relationship between
      macronutrients (especially fat and lipid release systems) and the secretion of
      gastrointestinal peptides that are involved with satiety and satiation. METHODS:
      The search was conducted in Medline (via Pubmed) using different combinations of
      MeSH terms and in the database LILACs using "DeCS". A selection of another
      articles relevant to the review topic was also examined. RESULTS AND DISCUSSION:
      At present, there are several laboratories and industries developing novel
      bioactive ingredients aimed at the regulation of food intake, with emphasis on
      those related with fat intake and the different ways in which fat can be
      technologically processed in order to create structures able to enhance satiety
      and/ or diminish hunger. CONCLUSION: These ingredients will be the future of
      functional foods focused on the prevention of weight gain and the support of
      other strategies against obesity (dietary, behavioral, etc...).

PMID- 25561098
TI  - [Hydrolyzable tannins; biochemistry, nutritional & analytical aspects and health
      effects].
AB  - INTRODUCTION: Hydrolysable tannins (HT) have been of scientific interest because
      of their nutraceutical potential. Both gallotannins (GT) and ellagitannins (ET)
      show different biochemical properties that result in various health benefits (eg
      anti-diabetic, anti-mutagenic, anti-microbial) for consumers, all associated with
      their antioxidant capacity (AOXc). OBJECTIVE: To analyze the most relevant
      aspects (biochemical, nutritional/analytical and health effects) of HT reported
      in the scientific literature. METHODS: A systematic search was conducted in
      several databases (PubMed, Cochrane, ScienceDirect) and free-access repositories
      (Google Scholar) on HT, GT and ET. This information was further sub-classified
      into biochemical, nutritional and analytical aspects (narrative review) and
      health effects (systematic review). RESULTS: The high molecular complexity and
      amount of hydroxyl groups (-OH) in both ET and GT, are responsible not only for a
      plethora of methods for extraction and purification but also for the several pro
      and anti-physiological effects of them such as enzyme inhibitions, protein
      excretion stimulation, AOXc and anti-proliferative effects. CONCLUSIONS: The
      association of ET/GT with several macromolecules present in foodstuffs and the
      digestive tract, counteract the AOXc of these compounds but conversely allow the
      differential distribution of GT and ET to different target organs in such way
      that their health effects seems to be different.

PMID- 25561099
TI  - [Mango: agroindustrial aspects, nutritional/functional value and health effects].
AB  - OBJECTIVE: To review and discuss the latest information on agroindustrial,
      functional and nutritional value of one of the most produced/consumed fruit crop
      in Mexico: The mango. METHODS: A search was conducted in several databases
      (PubMed, Cochrane, ScienceDirect) and public repositories (Google Scholar) on
      Mangifera indica L. This information was further sub-classified into
      agroindustrial, nutritional, functional aspects and health effects. RESULTS: One
      out of twenty mangoes consumed worldwide is Mexican. The variety "Ataulfo"
      variety is the most important crop. Minimal processing of its pulp (MP) generates
      peel (MC) and seeds as biowastes, which have nutraceutical potential. MP and MC
      are good sources of ascorbate, fructose, soluble (MP, starches and
      rhamnogalacturonans) and insoluble (MC, lignin and hemicelluloses) dietary fibers
      as well as functional lipids (MP). MP and MC are good sources of monomeric (MP)
      phenolic compounds (PC) such as gallic and protocatehuic acids and polymeric PC
      (MC) such as ?-PGG with associated anti-obesigenic, anti-inflammatory, anti
      carcinogenic and anti-diabetic potential. However, these benefits are dependent
      on their bioaccessibility (release from its food matrix) and metabolic fate
      (bioavailability). DISCUSSION: Mango is a valuable source of antioxidant
      compounds with proven health benefits. However, factors such as its variety,
      seasonality, pre and post-harvest handling, extraction of bioactives and some
      physiological barriers, can modify their nutraceutical potential.

PMID- 25561100
TI  - [Phospholipids: properties and health effects].
AB  - Phospholipids are amphipathic lipids, which are found in all the cell membranes,
      organized as a lipid bilayer. They belong to the glycerol-derived lipids, showing
      a similar structure as triglycerides. The current interest of them comes from its
      effectiveness to incorporate different fatty acids in the cell membrane, as they
      exhibit better absorption and utilization than triglycerides. In this paper, the
      bibliographical data published about the benefits of the phospholipids in
      inflammatory processes, cancer, cardiovascular diseases, neurological disorders,
      liver disease and as an antioxidants transporter is reviewed. 

PMID- 25561101
TI  - [Intragastric balloon: a review concerning alternative balloons compared to the
      classical ones (Bioenterics)].
AB  - Since de Tarpon Springs Consensus Conference in 1987, the Bioenterics
      Intragastric Balloon represents the standard model for obesity treatment with
      this technique. Nevertheless, over the last 30 years, especially for the last ten
      years, novel concept of balloons has appeared, as well as new alternative models,
      which are reviewed in this paper. 

PMID- 25561102
TI  - [Consensus document: nutritional and metabolic importance of cow's milk].
AB  - Cow's milk is a staple food for human consumption at all stages of life.
      Industrial processing has allowed widespread access to its consumption by the
      population, which has helped to significantly improve their health. From its
      composition point of view, milk is a complete and balanced food that provides
      high nutrient content in relation to its calorie content, so its consumption
      should be considered necessary from childhood to elderly. The benefits of cow's
      milk are not limited to its nutritional value, but extend beyond and are a factor
      of prevention in certain non communicable pathologies as cardiovascular disease,
      some cancers, high blood pressure or bone or dental pathology. It can also help
      in the fight against childhood overweight and obesity. In recent years we have
      seen a worrying decline in milk consumption among the Spanish population, at
      least in part influenced by misconceptions about its consumption and of other
      dairy products. This consensus document aims to review the current state of the
      topic regarding the effects of milk consumption on health, while making a call to
      the institutions and scientific societies to develop programs and information
      campaigns about the benefits of milk and dairy products consumption. 

PMID- 25561103
TI  - [Effectiveness of educational interventions conducted in latin america for the
      prevention of overweight and obesity in scholar children from 6-17 years old; a
      systematic review].
AB  - INTRODUCTION: Overweight and obesity are serious public health problem, which is
      specially among children populations. OBJECTIVE: To determine the effectiveness
      of educational interventions conducted in Latino America for the prevention of
      overweight and obesity in scholar children from 6 to 17 years old. Metodology:
      MEDLINE, LILACS and EMBASE were searched between february and may 2014 to
      retrieve randomized controlled trials and longitudinal studies that evaluated the
      effects of educational interventions intended to retrieve randomized controlled
      trials and longitudinal studies aiming to prevent overweight and obesity among
      Latinoamerican children. Risk of bias was evaluated using the PEDro scale and the
      CASPe tool. RESULTS: Twenty one studies were included (n=12,092). Different types
      of educational interventions were identified, such as nutritional campaigns,
      physical activity practice and environmental changes. Mixed approaches combining
      nutritional campaigns, physical activity promotion and enviromental changes were
      the most effective interventions, since their results produced the largest
      improvements in the overweight and obesity of children. None evidence of
      reporting bias was observed. CONCLUSION: Educational interventions performed in
      the educational environment that combined an adequate nutrition and the promotion
      of physical activity practice, are more effective for preventing overweight and
      obesity in Latino American children, although familiar interventions are also
      encouraged approach, associated with better responses on the behavioral change in
      scholar children.

PMID- 25561104
TI  - [Physical activity and accelerometer; methodological training, recommendations
      and movement patterns in school].
AB  - INTRODUCTION: Over the last years, the use of accelerometers has become relevant
      to quantify physical activity among youth. Methods used with accelerometers might
      modify the results and the possibility to compare different papers. These devices
      have been proved to be effective and valid quantifying long periods of physical
      activity compared to other methods. OBJECTIVE: To show methodological criteria
      regarding physical activity assessed by accelerometry with schoolars.
      METHODOLOGY: It was conducted a review of the literature related to
      accelerometers and scholar-aged subjects at PubMed from January 2002 to August
      2013, selecting 133 papers. RESULTS: As far as it is shown, it appears to be some
      tendencies related to the choice of attachment of the device, wearing time and a
      shorter epoch-length; however, it has been found a wide variability regarding the
      model of accelerometer and cutoff points used. DISCUSSION AND CONCLUSIONS: The
      different criterion used makes it difficult to compare methodological aspects
      among studies in spite of some papers carried out similar methods.

PMID- 25561105
TI  - [Information perceived by consumers through food labeling on fats: a systematic
      review].
AB  - OBJECTIVE: To review the scientific literature related to the information given
      to consumers about different types of fats in foods through food labeling.
      METHOD: Systematic review of the data found in MEDLINE (via PubMed), EMBASE,
      CINAHL, FSTA, Web of Science, Cochrane Library, SCOPUS and LILACS databasis,
      until September 2013. The terms used as descriptors and free text were "dietary
      fats", "dietary fats, unsaturated" and "food labeling". The limit "human" was
      used. RESULTS: 549 references were retrieved, of which 36 articles were selected
      after applying the inclusion and exclusion criteria. The main effects related to
      labeling information were linked to the price and place of purchase/ consumption,
      sensory dimensions, dietary habits, interpretation and education logo.
      CONCLUSIONS: Food labeling on fat content helps when making consumption
      decisions. Nutrition education and the meanings of food labels are essential and
      were effective although the "informed consumer" is yet to be achieved. Training
      activities should be directed towards prior beliefs and attitudes of consumers in
      order to make the health and nutrition message consistent. Food labels should be
      homogeneous and truthful in terms of expressing composition or presenting logos,
      and messages included in the packaging should be clear and not misleading.

PMID- 25561106
TI  - [Methods for evaluating large-scale nutrition programs in latin america: an
      integrative review].
AB  - INTRODUCTION: The evaluation of social programs is a field of knowledge in
      consolidation, involving different disciplines. It uses the social research tools
      but have particular goals that distinguish from it. OBJECTIVE: This study aimed
      to identify methodological designs currently used to evaluate the nutritional
      programs in Latin America, including the types of studies conducted on the
      assessments, the dimensions assessed and indicators used. METHODS: An integrative
      revision was carried out. Several electronic databases were consulted; likewise
      web pages of international agencies and institutions were searched by using a
      manual process. RESULTS: 92 evaluations of 40 programs were analyzed, we found
      that in most cases no explicit methodological design was used in the evaluation.
      In those cases where if do, mostly showed three designs: consistency and results,
      multidimensional model and triangulation of methods. The dimensions mostly
      assessed are the program's impact and outcomes and to a lesser extent its
      structure and process. The types of study used to measure the impact of
      nutritional programs remain quantitative in nature especially quasi-experimental,
      however there is an effort made by some scholars by using qualitative tools that
      account for the perceptions of the actors involved. CONCLUSIONS: We found an
      interest in some institutions for carrying out assessments based on new paradigms
      and exploring combination of methods, objectives and indicators.

PMID- 25561107
TI  - [Effects of beta-alanine supplementation on athletic performance].
AB  - Carnosine, dipeptide formed by amino acids beta-alanine and L-histidine, has
      important physiological functions among which its antioxidant and related memory
      and learning. However, in connection with the exercise, the most important
      functions would be associated with muscle contractility, improving calcium
      sensitivity in muscle fibers, and the regulatory function of pH. Thus, it is
      proposed that carnosine is the major intracellular buffer, but could contribute
      to 7-10% in buffer or buffer capacity. Since carnosine synthesis seems to be
      limited by the availability of beta-alanine supplementation with this compound
      has been gaining increasing popularity among the athlete population. Therefore,
      the objective of this study literature review was to examine all those research
      works have shown the effect of beta-alanine supplementation on athletic
      performance. Moreover, it also has attempted to establish a specific dosage that
      maximizing the potential benefits, minimize paresthesia, the main side effect
      presented in response to supplementation. 

PMID- 25561108
TI  - Effect of beta-glucans in the control of blood glucose levels of diabetic
      patients: a systematic review.
AB  - INTRODUCTION: Functional foods have been widely utilized to reduce the symptoms
      of various diseases such as diabetes mellitus (DM). Among the foods used to
      combat these effects are soluble fibres, mainly those rich in beta- glucans
      (BGs). OBJECTIVE: To review the effects of beta-glucans (BGs) on glucose
      plasmatic levels of diabetic individuals. DESIGN: A search was conducted using
      the Pubmed, Science Direct and Scielo databases using the keywords: diabetes
      mellitus and beta-glucan and glucose and glycaemia. As inclusion criteria, only
      studies on diabetic human individuals (type 1 or type 2) who consumed BGs were
      selected. RESULTS AND DISCUSSION: Of the 819 initial articles retrieved, only 10
      fit the inclusion criteria and were used in the study. It was observed that doses
      around 6.0g/person/ day, for at least 4 weeks were sufficient to provoke
      improvements in the blood glucose levels and also lipid parameters of individuals
      with DM. However, glucose levels do not reach normal levels using BG alone. Low
      doses of BG for at least 12 weeks were also reported to promote metabolic
      benefits. CONCLUSIONS: Based on previous research, it was concluded that the
      ingestion of BGs was efficient in decreasing glucose levels of diabetic patients.
      The consumption of greater doses or smaller doses for longer periods of time
      produced better results.

PMID- 25561109
TI  - Prevalence of obesity among primary students between 2009 to 2014 in China: a
      meta-analysis.
AB  - BACKGROUND: In recent years, obesity has become the major public health problems
      worldwide. The detection rate of obesity is alarmingly rising among children and
      adolescents in China, whose population of 120 million are in range of obesity. It
      was estimated that 8% of her children are obese. METHODS: Publications between
      2009 and 2014 on the obesity prevalence among primary school students in China
      were retrieved from PubMed, online Chinese periodical full-text databases of VIP,
      CNKI and Wanfang. Meta Analyst software was used to sum up and analyze the
      detection rates included in the previously retrieved literatures. RESULTS: After
      evaluation of the quality of the articles, 18 papers were finally included in our
      study, and the total sample sizes on the obesity investigation were 247547, in
      which 26466 were obesity. Meta-analysis findings showed that the pooled
      prevalence of obesity in primary school students is 10.0 %( 95% CI: 7.2%-13.5%).
      CONCLUSION: Our results indicated that the obesity prevalence status in China was
      still troublesome, for the situation will go worse if we currently fail to take
      effective and practical measures.

PMID- 25561110
TI  - [Consumption of sweetened, energy and alcoholic beverages among college students
      in the Mexico-US border].
AB  - BACKGROUND: The consumption of sugary, energy and alcoholic drinks among college
      students might be a health risk factor. OBJECTIVE: To assess the consumption of
      sugary, energy and alcoholic drinks and to determine their associations with body
      mass index (BMI) status among college students. METHODS: Second and third year
      college students enrolled in five different majors at the Universidad Autonoma de
      Baja California were evaluated. Weight, height and waist circumference were
      measured and BMI was calculated. A frequency questionnaire of 19 drinks was
      administered. RESULTS: A total of 1138 students participated in the study. The
      prevalence of obesity and abdominal obesity was 12 and 33% with 14 and 17% in
      women and men respectively. Fifty-five per cent of women and 68% of men consumed
      more than 25g of sugar drinks per day; 12% consumed more than 100g of sugar
      daily. The daily caloric intake from beverages was greater than 450kcal with
      350kcal in men and women respectively. Ten per cent of women and 15% of men
      consumed more than 30g of alcohol daily. The sugary drinks more frequently
      consumed were fruit juices (90%), whole milk (69%), regular soft drinks (83%),
      beer (37%), liquor (27%) and energy drinks (12%). CONCLUSIONS: Consumption of
      sugary, energy, and alcoholic drinks is very high, which may be a health risk in
      this population.

PMID- 25561111
TI  - [Obesity associated risk using Edmonton staging in bariatric surgery].
AB  - With a prevalence of Morbid Obesity of 1,2% of the Spanish population, the
      current criteria for Bariatric Surgery do not classify patients taking into
      consideration co-morbidities or functional status. We need new staging systems
      useful in predicting mortality and able to support prioritizing treatments. AIM:
      Applying Edmonton staging system to patients awaiting Bariatric Surgery. METHOD:
      Data collected from 81 patients from 2011- 2013 after pre-surgery protocol.
      Weight, height, waist, BMI, biochemical parameters and blood pressure are
      registered. Also taken down are hepatic, renal, osteoarticular diseases, sleep
      apnea syndrome and/or gastro-oesophageal reflux, if present. Edmonton staging of
      ten variables is applied to each patient. RESULTS: 81 patients: 67% women,
      average age 47y, 18% below 30y. Average BMI of 47, 90% of patients have a BMI
      >40. 34% of patients show sleep-apnea syndrome and 25% gastro-oesophageal reflux.
      9% of the patients have a BMI >45, diabetes mellitus and sleep-apnea syndrome.
      Applying the Edmonton Staging, nine patients (11%) are in the highest risk range
      (stage 3), 70% are in the high-risk range (stage 2) and 15 patients (18%) are
      included in the low-risk range. No patient was found to be in stage 0 without
      obesity risk factors. CONCLUSIONS: The Edmonton staging system provides us with
      information on presence or extent of co-morbidities that guide decision making in
      individuals. The mortality- predictive ability of Edmonton proposal could help to
      assist in determining the urgency of Bariatric Surgery and establish better
      criteria to prioritize these group of patients.

PMID- 25561112
TI  - [Weight misperception and physical fitness perception in relation to the physical
      activity level, dietary behaviour and psychosocial well-being].
AB  - INTRODUCTION: Most of the studies on weight misperception have been carried out
      in the US where it has been estimated that 20-40% of overweight or obese people
      underestimate their weight status. The perception of the physical fitness is a
      little studied variable but suggested as relevant in the adoption of healthy
      behaviours. OBJECTIVES: The aims were to analyze weight misperception and
      physical fitness perception in adolescents, evaluating the relationship between
      weight misperception and physical fitness perception and body weight management
      behaviours (diet and exercise) as well as to analyze the relationship between
      weight misperception and psychosocial well-being. METHODS: A total of 655
      students participated voluntarily in the study during which they completed a
      series of questionnaires. Weight and height of all participants were collected.
      RESULTS: Many young people misperceived their weight and its physical fitness.
      The majority of participants who were overweight or obese did not go on diet to
      manage their body weight. Those who overestimated their weight had the worst
      psycho-emotional state. DISCUSSION: The work is novel in Spain, it follows the
      methodology carried out in international studies on the same topic and the
      results are similar to those obtained in other populations. CONCLUSION: Weight
      misperception and physical fitness perception influence the adoption of healthy
      body weight management behaviors and is related to psychosocial well- being of
      young people.

PMID- 25561113
TI  - Prevalence of cardiovascular risk factors, the association with socioeconomic
      variables in adolescents from low-income region.
AB  - OBJECTIVES: To estimate the prevalence of obesity, overweight, abdominal obesity
      and high blood pressure in a sample of adolescents from a low-income city in
      Brazil and to estimate the relationship with the socioeconomic status of the
      family, the education level of the family provider and the type of school.
      METHODS: This cross-sectional study randomly sampled 1,014 adolescents (54.8%
      girls), between 14-19 years of age, attending high school from Imperatriz (MA).
      The outcomes of this study were: obesity and overweight, abdominal obesity and
      high blood pressure (systolic and/ or diastolic). The independent variables were:
      socioeconomic status (SES) of the family, education level of the family provider
      (ELFP) and type of school. The confounding variables were: gender, age and
      physical activity level. Prevalence was estimated, and the association between
      the endpoints and the independent variables was analyzed using a prevalence ratio
      (PR), with a 95% confidence interval, estimated by Poisson regression. RESULTS:
      The overall prevalence of obesity was 3.8%, overweight, 13.1%, abdominal obesity,
      22.7% and high blood pressure, 21.3%. The adjusted analysis indicated that girls
      with high SES showed an increased likelihood to be overweight (PR=1.71 [95% IC:
      1.13-2.87]), while private school boys had an increased likelihood of obesity
      (PR=1.79 [95% CI: 1.04-3.08]) and abdominal obesity (PR =1.64 [95% CI: 1.06
      2.54]). CONCLUSION: The prevalence of CVDR is high in adolescents from this low
      income region. Boys from private schools are more likely to have obesity and
      abdominal obesity, and girls with high SES are more likely to be overweight.

PMID- 25561114
TI  - [Design and implementation of a questionnaire to evaluate the dietary quality of
      school meals].
AB  - INTRODUCTION: The school canteen provides a substantial proportion of the daily
      nutritional intake for many children. There are nutritional standards for school
      meals, however, it is still difficult to assess the dietary quality. AIMS: To
      design a questionnaire for assessing the dietary quality of school meals, quickly
      and easily. METHODS: A dietary questionnaire (COMES) was designed on the basis of
      the current recommendations. COMES consist of 15 items related to the food
      frequency and to other characteristics of school meals. Then, a longitudinal
      prospective study was performed in order to analyze, with COMES, 36 school meals
      of 4 catering companies from Castilla y Leon during the academic years 2006-2007
      to 2010-2011. Differences in dietary quality menus according to the management
      system of catering companies (in situ vs. transported) were analyzed by using the
      Mann-Whitney and the Kruskal-Wallis tests. The significance was reached at p
      <0,05. RESULTS: The frequency intake of meat, dairy and prepared products was
      higher to the recommended in 97,2%, 94,4% and 27,8% of the analyzed menus,
      respectively. By contrast, the frequency intake of fish, fruit, legume, and
      vegetable garnishes were lower to the recommended in 83,3%, 94,4%, 91,7% and 75%
      of menus, respectively. Nevertheless, recommendations established by our
      consensus document for school meals are complied for all food groups, except for
      dairy and fruits. The variety of foods and culinary techniques were appropriate.
      No significant differences were found in the COMES score according to the
      management system (p=0,87), although catering system provides higher dietary
      quality. CONCLUSIONS: A new tool to assess quickly and easily the nutritional
      quality of school meals has been proposed. The assessment of the frequency intake
      of the most problematic foods for schoolchildren with this scale is much more
      demanding than the current recommendations. Even so, menus analyzed showed an
      acceptable quality in terms of variety of foods and culinary techniques, although
      milk frequency in the menus was excessive at the expense of fresh fruit. On the
      other hand, the transported system (i.e. catering, both hot and cold-holding)
      provides menus more consistent with the dietary recommendations.

PMID- 25561115
TI  - Evaluation of physical stability of all in one parenteral admixtures for
      pediatric home care with high electrolytes concentrations.
AB  - INTRODUCTION: The aim of the study was to evaluate stability of 48 total
      parenteral admixtures for pediatric patients who require home parenteral
      nutrition. Admixtures contain high amounts of electrolytes. In a clinical
      practice electrolytes-enrichment of the parenteral nutrition admixtures is a
      usual demand, especially on the neonatal/pediatric wards. The supplementation of
      parenteral nutrition with high concentration of electrolytes is a living problem
      due to decreased stability of lipid emulsions in nutrition admixtures caused by
      bivalent cations. METHODS: Preliminary admixtures were prepared in two-chamber
      ethylene vinyl acetate bags: amino acids, glucose and electrolytes were combined
      in one chamber and 20% (w/w) lipid emulsions (SMOFlipid(r), Intralipid (r) or
      ClinOleic(r)) were placed separately in the second chamber. Organic salts of
      calcium and phosphates were used. Pre-admixtures were stored at +4oC for up to 21
      days after preparation. Each composition of admixtures was prepared twice,
      because contents of the two chambers were combined at t=0 or after 21 days of
      storage at +4oC. Visual observations, globule size distribution (using optical
      microscopy, laser diffraction and photon correlation spectroscopy methods), pH
      analyses, zeta potential and surface tension were performed after combining all
      components together with vitamins. RESULTS: Among 48 of investigated admixtures
      only two were problematic and other may be stored for at least 21 days at 4
      degrees C and completed admixtures demonstrated stability for at least 24 h at
      room temperature. CONCLUSION: It was possible to obtain stable admixtures despite
      of the high concentration of electrolytes.

PMID- 25561116
TI  - Risk factors associated with iron depletion and parasites in preschool and school
      children of Arandas, Jalisco, Mexico.
AB  - OBJECTIVE: The objective of this study is to explore factors associated with iron
      depletion and parasites in preschool and school children attending the Instituto
      Alteno para el Desarrollo de Jalisco (INADEJ) and children who attend preschools
      and schools in Arandas, Jalisco. METHODS: This cross sectional study assessed two
      groups of children. In the INADEJ group, 102 children aged 60 to 144 months old
      were included, and in the School group of Arandas, Jalisco, 206 children were
      randomly selected from schools and preschools in the same municipality.
      VARIABLES: Ferritin concentration (MUg/ml), parasites, demographic,
      socioeconomic, educational and dietary data were collected. The Student's t test,
      U Mann Whitney, chi square, odds ratio and logistic regressions were estimated.
      RESULTS: Family income in the Schools group was $5,707 Mexican pesos (MP), which
      was higher than the family income in the INADEJ group ($4,311 MP), p = 0.031. The
      proportion of parents with incomplete primary education was higher in the INADEJ
      group (41.3%) than in the Schools group (35.4%) [OR = 1.88 (1.0-3.55)]. Unstable
      work was more frequent in the INADEJ group than in the Schools group [OR = 5.6
      (3.26-9.62)]. The ferritin concentration was lower in the INADEJ group than in
      the Schools group (25 MUg/L vs. 60 MUg/mL, respectively), p <0.001. Having
      giardiasis and two or more parasites was more common in the INADEJ group compared
      with the Schools group [OR = 7.2 (2.25-23.0)] and [RM 3.86 (1.35-10.98)]. Heme
      iron intake was lower in the INADEJ group. CONCLUSION: Low family income,
      father's job instability, lower levels of education, overcrowding, living with
      animals and lower consumption of heme iron were associated with parasites and
      iron depletion.

PMID- 25561117
TI  - Nutritional support teams: the cooperation among physicians and pharmacists helps
      improve cost-effectiveness of home parenteral nutrition (HPN).
AB  - INTRODUCTION: Modern home parenteral nutrition (HPN) requires the preparation of
      tailored admixtures. The physicians' demands for their composition are often at
      the variance with pharmaceutical principles, which causes the necessity of either
      the preparation of ex tempore admixtures or stability testing ensuring long shelf
      life. Both approaches are not cost-effective. The aim of the study was to use the
      cooperation among physicians and pharmacists to assure both: cost-effectiveness
      and patient-tailored HPN admixtures. METHODS: The first part of the study
      consisted of the thorough analysis of prescriptions for the most demanding 47 HPN
      patients (27 females and 20 males, mean age 53.1 year) treated at one HPN center
      to create few as possible long-shelf life admixtures. The second part of the
      study consisted of stability testing and modifications. RESULTS: The analysis
      showed over 137 variations needed to cover all macro- and micronutrients
      requirements. Their cost as ex-tempore solutions was extremely high (over 110 000
      EURO/month) due to logistics and similarly high if stability test for variation
      were to be performed (68 500 EURO). Therefore prescription was prepared de novo
      within team of physicians and pharmacists and four base models were designed.
      Water and electrolytes, particularly magnesium and calcium showed to be the major
      issues. Stability tests failed in one admixture due to high electrolytes
      concentration. It was corrected, and the new formula passes the test. Five basic
      models were then used for creation of new bags. Cost of such an activity were 3
      700 EURO (p<0.01) CONCLUSIONS: The cooperation within the members of nutritional
      support team could improve the cost-effectiveness and quality of HPN.

PMID- 25561118
TI  - [Food neophobia: impact on food habits and acceptance of healthy foods in
      schoolchildren].
AB  - INTRODUCTION: In children, food neophobia may affect food choices and limit the
      variety of the diet as well as affect the sensory acceptance of new foods.
      OBJECTIVE: To identify the impact of food neophobia in food habits and
      preferences of healthy food in school canteens users in the city of Murcia.
      MATERIALS AND METHODS: A total of 242 children in the second and third cycle of
      primary education (8-12 years), were included, stratified by sex and school year.
      A survey of habits and food preferences, food neophobia and acceptance of foods
      commonly consumed in the dining room was applied. In addition, a sensory test was
      conducted and the consumption of salads and fruits in the room was measured by
      the weighing method. RESULTS: The prevalence of neophobia was 16%, without
      difference by sex, academic year, time to use service, parental origin and being
      overweight or underweight. Food neophobia was associated with a detrimental
      effect on the consumption of vegetables and fruit, the taste for vegetables and
      lower consumption of cereals and cereal at breakfast and preferably less fruit
      and vegetables (p<0.05). A higher level of neophobia less acceptance was given to
      foods like chicken and lentils (p<0.05), fruit, salads and legumes (p<0.001).
      Food neophobia did not affect the hedonic acceptance of fruit and salads consumed
      in the cafeteria. CONCLUSIONS: It is necessary to integrate this information to
      stakeholders to ensure an improvement in the consumption of healthy foods.

PMID- 25561119
TI  - Relationships between serum calcium and magnesium levels and lipoproteins,
      homocysteine and insulin resistance/sensitivity markers at birth.
AB  - BACKGROUND: The relationship between serum minerals and homocysteine, lipoprotein
      and glucose homeostasis markers at birth has been scarcely reported. This study
      aims to determine a) the relationship between calcium, magnesium, cardiovascular
      disease (CVD) markers (e.g. lipids, lipoproteins, homocysteine) and insulin
      sensitivity/ resistance markers (e.g. glucose, insulin, HOMA) in cord serum; and
      b) to find out the possible influence of reduced or increased levels of serum
      calcium and magnesium on those markers. SUBJECTS AND METHODS: Forty-eight
      eutocic, normoweight and appropriated-for-gestational age, full-term, singleton
      without foetal distress newborns from the Merida Study were studied. Parameter
      percentiles for serum calcium and magnesium as well as for the Ca/Mg ratio were
      stated. CVD and insulin sensitivity/resistance markers in neonates within the
      first quartile for calcium, magnesium and their ratio were compared with those of
      neonates within the forth quartile for these minerals. RESULTS: Serum calcium
      negative correlated with HDL-c (p<0.05), arylesterase (AE) (p<0.01), the Apo
      A1/Apo B (p<0.05) and AE/HDL-c (p<0.05) ratios. Also, negative and significant
      correlations were found between the Ca/Mg ratio and AE (p<0.01), and AE/HDL-c
      (p<0.05). Neonates within the highest quartile for Mg displayed significantly
      higher levels of LDL-c and homocysteine (p<0.05). Newborns within the Ca/Mg ratio
      first quartile presented higher activities of AE while those of with high Ca/Mg
      ratio showed low levels of insulin. CONCLUSIONS: Calcium and magnesium levels
      appear related to CVD and insulin sensitivity/resistance markers at birth. Future
      follow-up studies, mostly in neonates, with high magnesemia and/or high Ca/Mg
      ratio at birth are recommended.

PMID- 25561120
TI  - [Study of the metabolic syndrome and obesity in hemodialysis patients].
AB  - INTRODUCTION: The metabolic syndrome (MS) consists of a set of clinical and
      biochemical changes. It is very common among chronic hemodialysis patients, being
      the leading cause of death in these patients, 44% of all patients undergoing this
      therapy. AIMS: The aim of this study was to investigate the prevalence of MS and
      risk factors associated with its development, as well as the prevalence of
      obesity in HD patients. METHODS: This study has followed 90 patients of both
      sexes with chronic renal failure (CRF) who were treated with hemodialysis
      periodically in our unit for ten years. All patients were performed quarterly
      measurements of plasma albumin (A1b) and other biochemical analysis; besides,
      they underwent some anthropometric measurements like weight, height and body mass
      index (BMI). This was calculated using weight / size2 formula and grouped in BMI
      values according to WHO criteria. The data concerning hypertension and glucose
      were also considered. RESULTS: The prevalence of MS was 25% and obesity was
      presented as follows: 45% with type I overweight; 30.8% with type II overweight
      and 12 patients (2%) were obese. Being statistically significant as risk factors,
      BMI, overweight, triglycerides, total cholesterol, HDL cholesterol as well as
      hypertension and elevated glucose levels were obtained. CONCLUSIONS: The
      metabolic syndrome compromises the patient survival causing a high prevalence in
      these patients. The principal risk factors in MS are monitoring weight, BMI,
      triglycerides, HDL cholesterol, hypertension and diabetes.

PMID- 25561121
TI  - [Effects of exenatide lar in type 2 diabetes mellitus and obesity].
AB  - INTRODUCTION: GLP-1 analogs have been shown to be an effective treatment of type
      2 diabetes mellitus (DM-2) and obesity. OBJECTIVES: Evaluate the efficacy of
      exenatide LAR on weight loss, glycemic control, blood pressure (BP) and lipid
      profile, in DM-2 and obesity. MATERIAL AND METHODS: Retrospective study of
      patients treated with exenatide LAR for 6 months. Demographic data (age, gender),
      anthropometric, fasting glucose, glycated hemoglobin (HbA1c), blood pressure and
      lipid profile were collected at baseline and at 6 months after treatment. We
      performed a logistic regression analysis to assess possible predictors of
      efficacy. RESULTS: 30 patients (17 male, mean age: 61.7 +/- 9.5 years old) with
      DM-2 of 9.7 +/- 6.2 years of evolution. HbA1c was reduced by 1.3% (95%CI 1.04
      1.57; p <0.001), weight by 2.8 kg (95%CI 1.67-3.96, p <0.001) and BMI by 1.9
      kg/m2 (95%CI 1,08-2,93; p <0,001). Total cholesterol decreased by 26.9 mg/dl
      (95%CI 9.23-38.8, p = 0.003), LDL cholesterol by 21.2 mg/dl (95% CI 7.56-34.9, p
      = 0.02) and triglycerides by 53.9 mg/dl (95%CI 46.4-77.1 mg/dl, p = 0.004). No
      statistically significant changes in blood pressure and HDL cholesterol were
      observed. 53.3% of patients got an HbA1c <7%, 66.6% lost weight, and 43.3%
      simultaneously achieved both of them. Neither of the studied variables was
      confirmed as a predictor of treatment response. Regarding side effects, 53.3%
      reported gastrointestinal discomfort (nausea) and 26.6% reported subcutaneous
      nodules of spontaneous resolution. CONCLUSIONS: Treatment with exenatide LA, in
      obesity and DM-2, has shown beneficial effect on lipid weight, BMI, glycemic
      control and lipid profile, despite the long duration of diabetes in our patients.

PMID- 25561122
TI  - Addition of dietary fiber sources to shakes reduces postprandial glycemia and
      alters food intake.
AB  - INTRODUCTION: Obesity and Type 2 diabetes may be controlled by foods capable of
      modulating food intake and blood glucose. OBJECTIVES: We investigated whether the
      addition of food sources of fiber or phaseolamin to shakes can control food
      intake and reduce postprandial glycemia. METHODS: This was a randomized, single
      blind, crossover design study (food intake: n=22; glycemia: n=10). Five liquid
      meals presenting similar amounts of macronutrients (C - control shake, OB - oat
      bran shake, F - flaxseed shake, WB - white bean extract shake, and UB - unripe
      banana flour shake) were consumed in five non-consecutive days. Participants kept
      dietary records during the subsequent 24 hours. Blood glucose was measured at 0
      (immediately before), 15, 30, 45, 60, 90 and 120 minutes after the ingestion of
      each shake and the incremental areas under the curves (iAUC) were calculated.
      RESULTS: Compared to C, there was a significant increase in fiber intake after
      the consumption of OB (+17.9g), F (+19.1g), and UB (+12.6g), and in fat after the
      consumption of OB (+25,4g). There was a non-significant reduction of daily energy
      intake in F compared to C (1524kJ; P=0.10). There was a 43% reduction in the iAUC
      (P=0.03) in response to UB consumption. CONCLUSIONS: Unripe banana flour reduced
      postprandial glycemic response of shakes almost by half. The effect of oat bran
      and flaxseed on food intake needs further investigation in long-term studies.

PMID- 25561123
TI  - Higher hdl levels are a preventive factor for metabolic syndrome in obese Turkish
      children.
AB  - AIM: The definition of childhood metabolic syndrome has not been described
      clearly. Childhood obesity is increasing gradually, and the incidence of
      childhood metabolic syndrome is also rising. We aimed to show metabolic syndrome
      components and preventive factors for metabolic syndrome in obese children
      Methods: In the present study, 187 obese children and adolescents 5-18 years old
      were investigated retrospectively. Demographic data, anthropometric measurements,
      body mass index, blood pressure values, insulin levels, oral glucose tolerance
      test results, total cholesterol, high density lipoprotein, and triglyceride
      levels were obtained from hospital records. A body mass index > 95th percentile
      was considered obese. Insulin resistance was calculated according to the oral
      glucose tolerance test with 1.75 g/kg glucose maximum 75 g glucose. The insulin
      sensitivity index and homeostatic model assessment-insulin resistance (HOMA IR)
      were calculated and compared. Metabolic syndrome was diagnosed according to the
      modified WHO criteria adapted for metabolic syndrome in children. RESULTS:
      Abnormal glucose homeostasis was detected in 53% of subjects. Dyslipidaemia was
      present in 45.7% and hypertension in 16.6% of the patients. Metabolic syndrome
      was identified in 24.6% of obese children and adolescents. High HOMA-IR values
      and fasting glucose levels, elevated triglycerides and lower HDL levels were an
      indication of metabolic syndrome. CONCLUSION: Obesity and insulin resistance are
      significant factors for the development of metabolic syndrome in children and
      adolescents. In obese children higher HDL levels are preventive factor for
      metabolic syndrome. Preventing obesity and insulin resistance may decrease the
      prevalence of metabolic syndrome.

PMID- 25561124
TI  - [Effect of consumption of bread with amaranth (Amaranthus dubius Mart. ex Thell.)
      on glycemic response and biochemical parameters in Sprague dawley rats].
AB  - INTRODUCTION: The incorporation of functional ingredients like amaranth
      (Amaranthus dubius Mart. ex Thell.) in bread making is a strategy to increase
      fiber intake, which is associated with beneficial health effects, improving
      glycemic response and lipid profile. MATERIALS AND METHODS: Thirty male Sprague
      dawley rats were randomized into three groups: diet of bread with 0% amaranth
      (PA0, control), diet of bread with 10% amaranth (PA10) and bread diet with 20%
      amaranth (PA20) for determining the feed intake, weight gain, triglyceride, total
      cholesterol, VLDL-C, LDL-C, HDL-C, protein and postprandial glycemic response.
      Data were analyzed using a completely randomized with 10 replications analysis,
      using the comparison test of Tukey for biochemical parameters. Postprandial
      glycemic response was analyzed by the method of repeated measures over time.
      RESULTS AND DISCUSSION: The daily intake and weight gain was not affected
      (P>0.05) in the groups with PA10 and PA20. The concentration of glucose,
      triglycerides and protein showed statistically significant differences (P>0.05)
      by the difference in content of amaranth diets. The values of total cholesterol,
      LDL-C, and atherogenic risk factor index were statistically significant (P.

PMID- 25561125
TI  - [Radiological percutaneous gastrostomy (GRP), 17 anos de experiencia, serie de
      casos del hospital Universitario Virgen del Rocio].
AB  - When assessing a patient nutritional support the state of the gastrointestinal
      tract is the most important point to consider, whenever possible we should choose
      the enteral nutrition (EN) over parenteral nutrition (PN) and recognized by its
      various advantages. The percutaneous gastrostomy (GRP) were introduced in
      clinical practice as an alternative to surgical gastrostomy (GQ). The speed,
      simplicity, low cost, low morbidity and low mortality of these techniques has
      allowed its rapid development.The feeding tubes types used were the balloon
      retained devices catheter, the pig tail and the ballon-retained with gastropexia
      (gastropexia). It is a retrospective study of all patients who were placed GPR in
      the Virgen del Rocio University Hospital, Sevilla, between September 1996 and
      September 2013, which aims to study is to describe the characteristics of
      patients and the complications presented for different types of enteral feeding
      tubes used. GPR 186 were performed in 176 patients (135 males (76.70%), with an
      average duration of 303.6 days, the most frequent diseases were cancers of the
      head and neck 49.46%. The types of feeding tubes used were pigtail 118 (63.44%),
      balloon-retained devices 22 (11.83%), and gastropexia 46 (24.73%). The most
      common early complications in the pigtail group were early purulent exudate and
      early bleeding (2.5 and 3.4% respectively), while in the balloon catheter group
      the initial output of the probe was most frequent early complication (13.7%),
      none of these complications were observed in the group of gastropexy. The most
      common late complication was obstruction probe. The GPR is a safe technique with
      lower mortality of 1%; Low frequently of early and late complications. A better
      understanding of this technique can reduce the frequency of complications. 

PMID- 25561126
TI  - [Study of tolerance and aceptability of a hyperproteic enteral formula enriched
      in fiber].
AB  - OBJECTIVES: To evaluate the gastrointestinal tolerance and acceptance of the new
      formulation of Isosource Protein (r) Fibre(r) with a new blend of fibers IS50(r).
      METHODS: Opened, non-comparative, nonrandomized, descriptive study in patients
      requiring full enteral tube feeding for at least 7 days. Gastrointestinal
      tolerance was assessed by daily record of subjective gastrointestinal symptoms by
      the patient, and objectives behind the abdominal exploration by the researcher
      for up to 15 days. RESULTS: 18 patients were included with a mean age of 67.32 +/
      13.8 years, of whom 66.7% were male. The average actual weight of the sample was
      68.7 +/- 9.8 kg (range: 51-90 kg) and BMI 24.0 +/- 4.0 kg/m2 (range: 16.0 to
      32.00 kg/m2). The average volume prescribed Isosource Protein(r) Fiber(r) was
      1580 +/- 282.7 ml / day (range: 1200 to 2000 ml/day). 72.22% of the patients
      received 1500 ml/day, received 16.67% 1750 ml / day, 5.56% received 2000 ml/day
      and 5.56% received 2500 ml/day. The analysis of the gastrointestinal tolerance of
      patients revealed that in the first study visit, reported no significant
      gastrointestinal problems, only one patient indicated the presence of mild
      constipation. By contrast, in the last study visit, it was observed that two
      patients reported constipation (mild to moderate) and two patients reported
      diarrhea (mild and severe). As for the evaluation of gastrointestinal tolerance
      by the investigator and depositional habit, the results show that in 100% cases
      tolerance was normal. Regarding the depositional habit, it was observed than the
      66.7% of patients had no bowel movements at baseline, compared to 33.4% at the
      last visit of the patient (p = 0.035). In this sense, a significant increase (p =
      0.035) in the mean number of daily bowel movements at the final visit (0.89 +/-
      0.90, range: 0-3) was observed, compared to the initial visit (0.44 +/- 0.78,
      range: 0-3). CONCLUSIONS: Isosource Protein(r) Fibre(r) has proved a formula for
      enteral nutrition well tolerated, with a very low frequency of gastrointestinal
      symptoms and an improvement in the number of stools, which encourages compliance
      with the standard prescribed by the health professional and suggest a positive
      effect on the regulation of intestinal transit.

PMID- 25561127
TI  - [Development of a gummy candy reduced in calories by sugar substitution with
      Stevia rebaudiana B].
AB  - The consumption of gummy candy is widespread among people of different ages but
      mainly by children. The formulation of this product requires sugar that
      contributes to their flavor and consistency, but with the undesirable effect of
      increase its glycemic index and its calories from simple sugars; it is known that
      consumption of products with these last two characteristics are related to
      childhood obesity, which is a worldwide growing disease. Stevia rebaudiana is a
      plant that naturally contains glycosides with high sweetening power and it is
      considered safe for consumption. Therefore the aim of this work was to develop a
      gummy candy reduced in calories by replacing sugar with Stevia rebaudiana B., and
      analyzes its texture and acceptability. Gummy candy were prepared with different
      percentage of sugar reduction (-20, -40, -60, -80 and -100%) and a product
      control (100% sugar); gummy elasticity was assess by displacement and maximum
      deformation, whereas resistance was evaluated by breaking strength; those gummies
      with better elasticity and resistance parameters underwent proximate analysis and
      sensory evaluations with a unstructured scale applied to 90 school children aged
      between 6 and 10 years old. A gummy candy reduced in calories with 60% sugar
      substitution with S. rebaudiana was developed; the level of satisfaction in
      school children was statistically the same respect to the gummy made of 100%
      sugar (p <0.05).

PMID- 25561128
TI  - [Levels of oxidative stress in serum and dietary behavior in adults in a rural
      area of Jalisco, Mexico].
AB  - INTRODUCTION: The feeding behavior establishes a relation of humans with food,
      includes food habits that could be involved with oxidative stress. OBJECTIVE: To
      evaluate the relation of indicators of oxidative stress (lipid peroxides) and
      antioxidant (ascorbic acid, catalase, superoxide dismutase) with feeding behavior
      in adults of Teocuhitatlan Corona, Jalisco, Mexico. METHOD: Study observational,
      descriptive, cross-sectional of 44 adults with 43 to 88 years, was used a
      instrument of feeding behavior. The questionnaire were related to indicators of
      oxidative stress. Were used descriptive statistics, frequency distribution and
      analysis of covariance with adjustment variables, was considered significant p
      <0.05. RESULTS: The values of serum lipid peroxides were related to behaviors:
      consider the nutritional content as most important when choosing food (p =
      0.042), dislike milk (p = 0.027), intake of sweets between meals (p = 0.001),
      habitual inclusion of vegetables and salads in main meal (p = 0.018). We do not
      found association in to values of ascorbic acid, cholesterol in low density
      lipoproteins and enzymatic activities of catalase and superoxide dismutase with
      food behaviors. DISCUSSION: The feeding behaviors analyzed in this study may be
      involved with development of oxidative stress and could be have protective or
      harmful effect in development to complications of chronic non-communicable
      diseases and aging in this population. This suggests to analyze demographic and
      socio-cultural aspects of region and besides analyzing the consumption and
      metabolic markers related to food.

PMID- 25561129
TI  - Effect of periodized water exercise training program on functional autonomy in
      elderly women.
AB  - BACKGROUND: Scientific evidence have been related negative functional autonomy to
      sedentary lifestyle in elderly women by other hand physical exercise is highly
      recommended to prevent deterioration of neuromuscular functions and proposed
      during the rehabilitation of physical disability and fall accidents. AIM: To
      determine the effect of periodized water exercise training on functional autonomy
      in elderly women. METHODS: Twenty-six subjects were randomly assigned in two,
      water exercise intervention group (n=16) and control group (n=10); The
      intervention group followed 12-week of periodized water exercise training program
      five times a week, 30 minutes of water exercise with work heart rate reserve of
      40-50% (1-6th week) increasing the load to 50-60% (7-12th week); The protocol of
      the Group of Latin-American Development for Maturity (GDLAM) was used to evaluate
      functional autonomy; As statistical analyses mixed 2 x 2 ANOVA was used, also
      percentage changes (Delta %) were calculated. RESULTS: The results showed
      significant improvement (p<0.05) comparing the interaction intergroup and the
      measurements in 10 meters walk test (10mW) (p=0.001) and general GDLAM index (GI)
      (p=0.012), percentage changes (Delta %) showed positive improvements in the five
      components of (GDLAM) and (GI). CONCLUSION: Periodized water exercise training
      program was able to enhance (10 mW) and (GI) however, will be appropriated in the
      future more studies to better clarify the possibilities of improvements between
      water exercise and functional autonomy.

PMID- 25561130
TI  - [Relationship between sleep and constipation in the elderly Chileans].
AB  - BACKGROUND: There is scarce information about constipation in elderly subjects.
      Among the variety of factors causing constipation, the sleeping hours are a
      factor usually not taken into account. OBJECTIVES: To determine the association
      between hours of sleep during the week and weekend, with constipation in older
      adults. DESIGN: Sleep quality, stool consistency, physical activity (PA) and
      dietary fiber intake was assessed using various validated surveys in 424 healthy
      autonomous elderly men and women, living in Santiago, Chile. RESULTS: Half of the
      participants reported having abnormal stools (constipation and diarrhea).
      Subjects who had constipation had lower PA and greater difficulty falling asleep
      than subjects with normal bowel movements. The elderly participants with
      constipation had a higher amount of sleep during the week and weekend, that
      subjects with normal bowel movements (9.4 +/- 1.6 vs 8.8 +/- 1.8 hours, p =
      0.013). The constipated subjects slept significantly more than those with normal
      evacuation (9.7 +/- 1.5 vs 9.2 +/- 1.8, p = 0.024). No differences in the
      nutritional status and fiber intake among patients with different consistencies
      were found. CONCLUSIONS: There is an association between sleep and the
      consistency of the stools in elderly patients. It would be interesting to
      evaluate whether long-term improvement of these factors could have a positive
      impact on the other.

PMID- 25561131
TI  - Nutritional status, muscle mass and strength of elderly in southern Brazil.
AB  - AIMS: to assess and compare nutritional status and functional capacity of elderly
      goers of groups for guided physical activity or for guided recreational
      activities. METHODS: Cross-sectional study with 210 elderly (60 years old or
      more) of coexistence groups (for physical or recreational activities).
      Nutritional status was assessed by the Mini Nutritional Assessment and Body Mass
      Index. Muscle mass was estimated by calf circumference (cut point of 31cm for
      both genders) and strength was evaluated by hydraulic dynamometer, which measures
      the opponent's finger maximal strength. The study was approved by Research Ethics
      Committee. RESULTS: Were enrolled 106 elderly in recreational group and 104 in
      physical activity group. Most of the sample (86.7%) were female. The mean age was
      69.3 years old. Body Mass Index showed 82.9% of seniors with excessive weight
      (87.7% in recreational and 77.9% in physical activity group, p=0.04). When
      assessed by Mini Nutritional Assessment, 22.9% was classified as malnourished or
      at risk of malnutrition, with no difference between groups. The mean calf
      circumference was 37.3 +/- 4.1 cm, decreasing significantly with aging (p=0.05)
      and being higher in elderly with higher BMI (p=0.001). Calf circumference was
      also greater in physical activity group. Muscle strength's mean was 6.77 (IQR:
      5.83, 7.90) kg, with significantly higher values among men. There was no
      significant variation between age, nutritional status or between groups.
      CONCLUSIONS: This study presented as its main findings that most seniors showed
      no nutritional risk, with high prevalence of overweight. The practice of physical
      activities was associated with greater CP and greater functionality of the
      opposing finger muscles, which indicates the importance of maintaining physical
      activity in the aging process, in order to prevent frailty and disability.

PMID- 25561132
TI  - Breast cancer and body image as a prognostic factor of depression: a case study
      in Mexico City.
AB  - INTRODUCTION: Being diagnosed with breast cancer is devastating for women because
      they face a "sense of loss". Since this loss is observed by the women themselves
      as well as by those around them, this can often lead to depression. OBJECTIVES:
      (1) To verify a possible association between body image and depression; (2) To
      establish a relation between depression and time since breast cancer diagnosis.
      METHOD: The data came from the Beck Depression Inventory (BDI-II) and the Body
      Image Scale (BIS), which were used to evaluate the subjects. A random sample of
      n=120 women was divided into two groups. The women in Group 1 had been recently
      diagnosed with breast cancer, but had not at that time had any type of surgical
      treatment. The women in Group 2 had undergone a mastectomy over a year ago.
      RESULTS: The women in Group 1 were found to be more severely depressed, and a
      statistically significant association was detected between depression and body
      image (p0.05). CONCLUSIONS: The women in Group 1, the majority of whom were
      suffering from severe depression, had a disturbed body image even though they had
      not had a mastectomy. The women in Group 2, who had been operated, also suffered
      from similar body image problems, but their depression was not as intense.

PMID- 25561133
TI  - Transient hyperthyroidism after total laryngectomy for laryngeal cancer.
AB  - INTRODUCTION: Thyroid damage is a complication of total laryngectomy (TL) and may
      be caused by manipulation of the gland. There are isolated descriptions in the
      literature related to transient hyperthyroidism (HT) post-head and neck surgery.
      The aim of this study was to determine the frequency of HT after TL and to
      evaluate its relationship with the surgical procedure. METHODS: Retrospective
      cohort study. Forty-four patients were included and stratified in Group 1 (TL +
      pharyngectomy), and Group 2 (TL + neck dissection). Post-op thyroid function was
      measured in all patients. Results were analyzed with chi square plus Yates and OR
      (p<0.05). RESULTS: Twenty-four patients (54.6%) developed HT, with a mean TSH
      0.11+/-0.09 uU/ml and a median FT4 1.5 ng/dl (1.2-1.8, IQR 0.30). Four patients
      (16.6%) required a pharmacological approach, because of their clinical course.
      Patients in Group 1 showed significantly more hyperthyroidism compared to Group 2
      (p=0.04, OR 4, CI 95% CI,1.03-15.53). All became euthyroid before discharge.
      CONCLUSION: We found a high prevalence of HT after TL, and it was related indeed
      to the surgical procedure. All patients became euthyroid before discharge. We
      suggest to check thyroid function in routine lab tests in this setting. The
      hypothetical repercussion of these findings on resting energy expenditure and
      haemodynamics requires further studies.

PMID- 25561134
TI  - [Physical fitness level and its relationship with body weight status in school
      children].
AB  - OBJECTIVE: To explore and establish possible relationships between body weight
      status and fitness level in a sample of primary school children. METHODS:
      Descriptive and cross-sectional study. A total of 216 students (125 women 8-11
      years) participated in the assessment of weight, height and physical condition.
      The body weight status (normal-weight, overweight and obesity) was categorized
      according to international standards. RESULTS: males have on average higher
      values in the running test 4x10 meters, manual dynamometry, longitudinal jump and
      Course-Navette. Women show a higher tendency to exceed healthy weight. The
      analysis showed that a high level of fitness is directly associated with normal
      weight status (p <.01). CONCLUSIONS: The results of this study suggest that
      students who have higher fitness levels are more likely to have a body weight
      status within normal parameters. Programs promoting physical activity, aimed to
      improve fitness, and thus the body status need to be implemented. Increasing
      physical education time at school or conducting educational programs focused on
      nutrition can be effective measures to improve overall health.

PMID- 25561135
TI  - [Effect of phlebodium decumanum and coenzyme Q10 on sports performance in
      professional volleyball players].
AB  - INTRODUCTION: Physical training programmes are based on provoking transitory
      states of fatigue in order to induce super compensation by the biological systems
      involved in the activity, in order to improve the athlete's medium-long term
      performance. The administration of nutritional supplements with antioxidant and
      immunomodulatory properties, such as Phlebodium decumanum and coenzyme Q10, can
      be a very advantageous means of achieving recovery from the inflammation and
      tissue damage caused by the stress of prolonged, intense exercise. METHODOLOGY:
      An experimental, longitudinal, double- blind experiment was conducted, with three
      randomised groups obtained from a sample of 30 male volleyball players (aged 22
      32 years) at the University of Granada, with a high level of training (17 hours a
      week during the 6 months preceding the study). The effects were then evaluated of
      a month-long physical training programme, common to all the study groups,
      associated with the simultaneous administration of the following nutritional
      supplements: Phlebodium decumanum (4 capsules of 400 mg/capsule, daily),
      Experimental Group 1; Phlebodium decumanum (same dose and schedule as Group 1)
      plus coenzyme Q10 (4 capsules of 30 mg/ capsule, daily), Experimental Group 2; a
      placebo substance, Control Group. The following dependent blood variables were
      examined to assess the effects of the intervention on the basal immune and
      endocrine-metabolic profile: cortisol and interleukin-6, both related to the axis
      of exercise-induced stress; and lactic acid and ammonium, related essentially to
      the anaerobic metabolism of energy. RESULTS: All the study groups presented
      favourable adaptive changes with respect to the endocrine-metabolic and immune
      profile, as reflected by a significant decrease in the post-test concentrations
      of cortisol, interleukin 6, lactic acid and ammonium, compared to the values
      recorded before the physical activity with/without nutritional supplement, per
      protocol. The groups that achieved the most favourable profile were those which
      had received nutritional supplementation, rather than the placebo, and among the
      former, those which had received the double- strength supplement with Phlebodium
      decumanum plus coenzyme Q10. CONCLUSIONS: The intake of Phlebodium decumanum plus
      coenzyme Q10 for 4 weeks produced protective effects on the endocrine-metabolic
      and immune profile, which we attribute to the immunomodulatory and antioxidant
      properties of these substances, which are highly beneficial not only in terms of
      delaying fatigue and improving athletic performance, but also in reducing the
      risk of injuries associated with high intensity exercise.

PMID- 25561136
TI  - [Achievement of physical activity healthy guidelines in hypertensive adults].
AB  - INTRODUCTION: It seems necessary to educate patients in the need of realize the
      importance of physical activity to improve their health, and specifically, about
      the important implications that the intensity of physical activity has for health
      and fitness benefits. OBJECTIVE: The aim of this was to evaluate achievement of
      physical activity recommendations for health in a group of hypertensive
      controlled patients from two primary care centers: La Estacion y La Algodonera
      located in Talavera de la Reina (Toledo). METHODS:  DESIGN: Cross-sectional
      study. LOCATION: Primary care centers: La Estacion y La Algodonera located in
      Talavera de la Reina. PARTICIPANTS: A total of 80 controlled hypertensive
      patients aged 40 to 60 years old who met the inclusion criteria were invited to
      the study. A sample of 52 patients obtained valid results to enter the study.
      MAIN MEASURES: Minutes of Moderate to vigorous physical activity (MVPA), minutes
      of light activity and number steps were measured. Data was displayed by gender
      and weekdays vs weekend days. RESULTS: Only 59.6% of patients achieved the
      minimum recommendation of 30 minutes of MVPA at least every day to improve
      health. Male achieved significantly more MVPA during the weekend than female did.
      Only women presented significant differences between MVPA during week days vs
      weekend days. CONCLUSIONS: 59.6% of hypertensive controlled patients of our
      sample achieve the minimal physical activity recommendations for health; the rest
      of the sample should increase their physical activity to achieve the
      recommendation and to improve their blood pressure levels.

PMID- 25561137
TI  - [Effect of training intensity on the fat oxidation rate].
AB  - INTRODUCTION: Physical exercise is a key modulator of the maximum fat oxidation
      rate (MFO). However, the metabolic transition zones in the MFO-exercise
      relationship are not generally considered for training prescription. Objective.
      To examine the effects of training in different metabolic transition zones on the
      kinetics of MFO and its localization (Fatmax) in young physically active men.
      METHODS: 97 men were divided into 4 similar sized groups, 3 experimental groups
      and a control group (CG). Subjects in each experimental group undertook an 8-week
      running program. Training was continuous at the intensity of the aerobic
      threshold or VT1 (CCVT1); or performed as intervals at the intensity of the
      anaerobic threshold or VT2 (ITVT2); or at maximum aerobic power VO2max
      (ITVO2max). Before and after the training intervention, expired gases were
      monitored in each subject to determine VO2max, VT1, VT2, MFO (by indirect
      calorimetry) and Fatmax. RESULTS: In response to training, experimental groups
      showed an increase in MFO (from 16,49 to 18,51%; p<0,01) and a mean reduction in
      Fatmax of 60,72+/-10,52 to 52,35+/-7,61 %VO2max (p<0,01). No changes of interest
      were observed in the control subjects. Intergroup comparisons revealed no
      differences in MFO and Fatmax among the experimental groups, though compared to
      the CG, a greater reduction in Fatmax was observed in CCVT1 (p<0,05). No changes
      were detected in performance except a drop in VO2max in the GC (p<0,05).
      CONCLUSION: 8 weeks of training led to an increase in MFO and reduction in Fatmax
      irrespective of training intensity.

PMID- 25561138
TI  - [Effects of beta-alanine supplementation on wingate tests in university female
      footballers].
AB  - INTRODUCTION: Football is a sport that develops actions intermittent high
      intensity exercise using the anaerobic pathway, for that reason, the muscle
      fatigue would produce primarily by increasing acidosis. Carnosine, which is
      formed from L-histidine, beta-alanine, has proven to produce an effect "buffer"
      of acidosis. OBJECTIVE: To determine the effect of beta-alanine supplementation,
      on three successive Wingate tests and compare the average power, maximum power
      and lactate blood in selected female college soccer. METHODS: We evaluated 10
      football players who were three Wingate, 5 min rest between each sprint,
      determining the average power, maximum and lactate at the end of each test, then
      consumed 2,4 gr/day of beta-alanine for 30 days and repeated the tests. The
      control group (n=8) performed the same tests, but without consuming the
      supplement. Monark cycle ergometer was used (Ergomedic 874E) and to measure
      lactate the Lactate Pro 2. RESULTS: The group with supplementation significantly
      improved mean power difference from the control group. The maximum power improved
      only in the first sprint unlike the control group and Lactate did not differ.
      DISCUSSION: The evidence shows that the beta-alanine improves performance on
      tests of more than 30 second long, but in our study improves average power and
      peak power even when performing consecutive sprint, being able to emulate the
      reality of the football game.

PMID- 25561139
TI  - [The height target prediction by the Tanner method infra evaluates the final
      height in youths from the rural area of South East Spain].
AB  - INTRODUCTION: Assessing the final height of an individual before the end of the
      growth has clinical utility for monitoring child health. OBJECTIVE: To calculate
      the target height of a rural population in Southeast Spain and to compare it with
      the final height. METHODS: A descriptive observational study was performed. 50
      young adults were included in the study (44% men) along with 100 biological
      parents. The selection of young adults was conducted in 2 phases: 1.
      Retrospective study based on medical records. 2. PROSPECTIVE STUDY: recruitment
      and anthropometric measurements. Target size and the size deviation were
      calculated. RESULTS: The final height was 4.44 cm and 6.37cm higher than the
      expected target height for men and for women, respectively (p<0.001). (p<0.001).
      The genetic influence differed between males and females, while the final height
      for males was associated with the paternal height (r = 0.613, p <0.01), for
      females, no significant association with the height of the father or the mother
      was found. The age of the greater correlation with the final height was at 10 ys
      for boys (r = 0.819) and at 14 ys for girls (r = 0.959). The males' final obesity
      degree correlated with the father's BMI (r = 0.575, p <0.01) and for girls, with
      the mother's (r = 0.451, p <0.05). CONCLUSIONS: The target height formula
      underestimates the final size of individuals. It could be useful to perform an
      anthropometric study at 10 ys in boys and at 14 ys in girls in order to prevent
      further alterations in size or weight.

PMID- 25561140
TI  - [State of food and nutritional care in public hospitals of Ecuador].
AB  - RATIONALE: The ELAN Ecuadorian Study of Hospital Malnutrition returned a
      malnutrition rate of 37.1% in public hospitals of Ecuador [Gallegos Espinosa S,
      Nicolalde Cifuentes M, Santana Porben S; para el Grupo Ecuatoriano de Estudio de
      la Desnutricion Hospitalaria. State of malnutrition in hospitals of Ecuador. Nutr
      Hosp (Espana) 2014;30:425-35]. Hospital malnutrition could be the result of
      institutional cultural practices affecting the patient's nutritional status.
      OBJECTIVES: To present the current state of food and nutritional care provided to
      patients assisted in public hospitals of Ecuador. MATERIAL AND METHOD: The state
      of food and nutritional care provided to 5,355 patients assisted in 36 hospitals
      of 23 provinces of the country was documented by means of the Hospital Nutrition
      Survey (HNS), conducted as part of the ELAN Study. HNS recorded the completion of
      nutritional assessment exercises, the use of food-bymouth, fasting, use of oral
      nutritional supplements, and implementation and conduction of Artificial
      nutritional schemes (Enteral/Parenteral); respectively. RESULTS: Less than 0.1%
      of clinical charts had a diagnosis of malnutrition included in the list of the
      patient's health problems. Less than half of the patients had been measured and
      weighted on admission. Serum Albumin values and Total Lymphocytes Counts were
      annotated on admission in only 13.5% and 59.2% of the instances, respectively.
      Current weight value was registered in only 59.4% of the patients with length of
      stay 3 15 days. An oral nutritional supplement was prescribed in just 3.5% of non
      malnourished patients in which significant metabolic stress and/or reduced food
      intakes concurred. Although up to 10 different indications for use of Artificial
      nutrition were identified in the sample study, any of these techniques was
      administered to just 2.5% (median of observed percentages; range: 1.3 - 11.9%) of
      surveyed patients. CONCLUSIONS: Currently, nutritional status of hospitalized
      patient is not included within therapeutic goals, nutritional assessment
      exercises are incomplete, and Artificial nutrition is not considered a
      therapeutic option. From these findings it can only be concluded that the
      nutritionist still has no place within medical care teams. Adoption of required
      measures in order to introduce "Food and Nutrition Good Practices" into the
      medical care in public hospitals of Ecuador is urgently needed.

PMID- 25561141
TI  - [Food habits and health-related behaviors in a university population].
AB  - INTRODUCTION: The university population is considered a particularly vulnerable
      group from the nutritional point of view as it begins to take responsibility for
      their food and going through a critical period in the consolidation of habits and
      food-related behaviors. Previous studies highlight the loss of healthy dietary
      patterns and the need to develop educational and nutritional interventions.
      OBJECTIVES: To analyze habits and food-related behaviors in a university
      population in Catalonia as a starting point to develop effective strategies for
      health promotion. METHODS: Cross-sectional observational study of dietary habits
      and food-related behaviors (alcohol, tobacco and physical activity) in Catalan
      university students. RESULTS: Lunch and dinner at home were the essential meals
      of the surveyed students while breakfast and afternoon snack were omitted about
      20% of cases. The obtained dietary pattern was characterized by an excessive
      consumption of red meat (84%) and poor or very poor consumption of vegetables
      (39.8%), cereals (92.6%) and fruit (73.9%). The consumption of alcohol was low,
      and the most consumed beverage was beer. The majority of students reported not
      being regular smokers. Among regular smokers predominated women. Alcohol
      consumption was also low and beer was the most consumed beverage. A considerable
      number of students were used to performing moderate or intense physical activity
      three or more times a week, although a similar proportion not perform any
      physical activity regularly. DISCUSSION AND CONCLUSIONS: In the studied
      population, food habits that deviate from the recommendations of the
      Mediterranean Diet are detected in a large number of students: low consumption of
      fruits and vegetables, increased consumption of dairy products and a predominance
      in the consumption of red meat in front of poultry. These changes are in line
      with those that occurred in recent years in Spain and in other industrialized
      countries.

PMID- 25561142
TI  - Macronutrients and energy content of oral hospital diet prescribed to chronic
      kidney disease patients on conservative treatment.
AB  - INTRODUCTION: The contribution of diet and treatment planning in the treatment of
      Chronic Kidney Disease (CKD) has been recognized as having a significant clinical
      impact if introduced early. OBJECTIVE: determine the levels of carbohydrates,
      proteins, lipids, energy and energy density (ED) in an oral hospital diet
      prescribed to CKD patients, and to evaluate the adequacy of this diet with
      respect to dietary recommendations. METHODS: Diets were collected in a Brazilian
      public hospital on two non-consecutive days of six different weeks. The
      carbohydrate, protein, and lipid (total, saturated, monounsaturated,
      polyunsaturated, linoleic, linolenic and trans fatty acids) contents were
      determined in a laboratory. The amount of energy and the ED of the diets were
      calculated using the correction factor Atware and by dividing the total energy of
      the diet by weight, respectively. RESULTS AND DISCUSSION: About 14.3% of the
      diets produced for patients with CKD were analyzed. The average density of the
      diets was low (0.7 kcal/g). In terms of nutritional adequacy, the average lipid
      content (15%) and linolenic fatty acid content (0.4%) were below the
      recommendation, as was energy (23.4 kcal / kg / day). The average carbohydrate
      content (63.5%) and protein content (1.0 g/kg/day) exceeded the recommendations
      levels. CONCLUSION: The oral hospital diet prepared for patients with CKD were
      considered unbalanced, and an unfavorable clinical treatment for these patients.

PMID- 25561143
TI  - [Frequency of eating away-from-home and quality of dietary carbohydrate and fat
      intake in the SUN Project].
AB  - OBJECTIVE: To investigate the association between eating- away-from-home (EAFH)
      and a) the quality of dietary carbohydrate intake and b) the quality of fat
      intake. MATERIAL AND METHODS: We assessed 19,371 participants in the SUN cohort
      who completed a validated baseline food frequency questionnaire. Quality indices
      of carbohydrate (CQI) and fat (FQI) were used. Multiple regression models were
      fitted to determine the association between the frequency of EAFH (4 categories)
      and both indices. Logistic regression analysis was used to assess the association
      between the frequency of EAFH and low CQI or FQI ((<25th percentile). RESULTS:
      Participants showed an average CQI and FQI of 11,3 (SD 3,2) and 1,7 (SD 0,5),
      respectively. A higher frequency of EAFH (>= 2 times/week) was associated with a
      poorer CQI and a poorer FQI. For CQI, the adjusted mean difference was -0,29,
      95%CI: -0,41, -0,17 (p for trend <0,001), and for FQI it was -0,02, 95%CI: -0,03,
      -0,001 (p for trend 0,03). Participants with a highest frequency (>= 2
      times/week) of EAFH had higher adjusted risk of a poorer CQI, (adjusted OR 1,31,
      95%CI 1,17, 1,46, p for trend <0,001), but this habit (EAFH) was unrelated to FQI
      (adjusted OR 0,93, 95%CI: 0,83, 1,03, p for trend 0,194). KEY FINDINGS: A higher
      frequency of EAFH was associated with a poorer quality of dietary fat, and
      particularly, dietary carbohohydrate. These findings highlight the importance of
      nutritional education addressed to consumers who frequently do out-of-home meals.

PMID- 25561144
TI  - [Food insecurity and social vulnerability in chiapas : the face of poverty].
AB  - OBJECTIVE: To estimate the frequency, distribution, and trends of food
      security/insecurity conditions of families in Chiapas and their relationship with
      low income factor and sociodemographic characteristics. METHODS: Retrospective
      and cross-sectional descriptive study. Information of 1430 households from The
      National Health and Nutrition Survey 2012 was included. The Food Insecurity was
      measured using the harmonized version of the Latin and Caribbean Food Security
      Scale for Mexico. RESULTS: 83% of households in Chiapas has some type of food
      insecurity, 86.5% is concentrated in the lower socioeconomic levels, 85% of
      households in rural areas have food insecurity, 87% of households beneficiary of
      Oportunidades still have food insecurity. DISCUSSION: A large part of this
      population continues to have high levels of Food Insecurity. Clearly targeted
      social programs designed to eliminate this lag, fail to reduce levels of access
      to food which affects the physical and intellectual potential development of
      Chiapas people, becoming an obstacle to the development of the State.
      Reorientation of food policy in Mexico is considered.

PMID- 25561146
TI  - The presence and accuracy of food and nutrition terms in the Spanish and English
      editions of Wikipedia: in comparison with the Mini Larousse encyclopaedia.
AB  - OBJECTIVES: To determine the presence and appropriateness of the terminology
      concerning Food/Nutrition Science in the Spanish and English editions of
      Wikipedia and to compare them with that of an encyclopaedia for general use (Mini
      Larousse). Methods: The terms in the study were taken from the LID dictionary on
      metabolism and nutrition: The existence and appropriateness of the selected terms
      were checked through random sample estimate with no replacement (n=386), using
      the Spanish and English editions of Wikipedia. RESULTS: The existence of 261
      terms in the Spanish edition and 306 in the English edition was determined from
      the study sample (n=386). Several differences were found between the two editions
      (p<0,001). There were differences between the two editions in relation to the
      appropriateness of definitions, though these were not studied in any depth
      (p<0,001). During the study of the 261 terms in the Spanish version of
      Wikipedia,3 entries (1,15%, IC95%: 0,00-2.44) were found to be lacking in
      appropriate information; 2 of the 306 entries in the English edition failed to
      give appropriate information (0,52%, IC95%: 0,00-1,23). A comparison between the
      existing entries of the Mini Larousse Encyclopaedia and the Spanish edition of
      Wikipedia, showed Wikipedia (p<0,001) as having a larger number of entries.
      CONCLUSIONS: The terminology under study is present to a lesser extent in the
      Spanish edition of Wikipedia than in the English edition. The appropriateness of
      content was greater in the English edition. Both the Spanish and English editions
      have a greater number of entries and more exact ones than the Mini Larousse.

PMID- 25561145
TI  - Glycemic response to carob (ceratonia siliqua L) in healthy subjects and with the
      in vitro hydrolysis index.
AB  - The purpose of this study was to determine the in vivo glycemic index of carob
      tablets with healthy subjects and to determine the in vitro glycemic index of
      carob tablets and carob flour by the hydrolysis index. Seven healthy volunteers
      consumed portions of carob tablets containing 26g of available carbohydrate.
      Their capillary blood was taken at intervals after carob or glucose consumption.
      The glycemic hydrolysis index by an in vitro technique was based in the release
      of glucose after enzymatic treatment of carob tablets and carob flour. The
      determination of the fiber content was performed using the enzymatic- gravimetric
      method. By the in vivo determination, the estimated glycemic index of carob
      tablets could be considered low (<= 55). By the in vitro determination, the
      estimated glycemic index ranged from 40.1+0.02 of carob tablets to 40.6+0.05 of
      carob flour. The total fiber values obtained for carob flour samples were from
      42.6% +/- 0.49 to 42.9% +/- 0.68 with no statistical significant differences
      between samples. Carob tablets and carob flour could be classified as low
      glycemic index food and low glycemic load food. Carob flour is a high fiber food,
      containing mainly high levels of insoluble fiber. 

PMID- 25561147
TI  - Role of ApoA1 on high-density lipoprotein: an intervention with plant sterols in
      patients with hypercholesterolemia.
AB  - BACKGROUND: Numerous studies have shown an inverse association between
      cholesterol's concentration associated with High-Density Lipoprotein Cholesterol
      (HDL-C) and cardiovascular risk. The present study intends to investigate the
      possible relation between Apolipoprotein A (ApoA1) and HDL-C as a new strategy to
      reduce cardiovascular risk. AIM: was determine the effect of ApoA1 in cholesterol
      's metabolism through its influence on HDL-C in young adult population. METHODS:
      One clinical trial, controlled, randomized, double-blind, providing a commercial
      milk, "Naturcol", with sterols for 3 weeks (n = 19) and placebo (n = 16). A
      questionnaire Ad Hoc was designed and a complete anthropometric study was made.
      SPSS 21.0 was used to analyse the data. RESULTS: Significant differences were
      observed between sterol milk and placebo in a single marker, Low-Density
      Lipoprotein Cholesterol (LDL-C). A linear dispersion of data between HDL-C and
      ApoA1 was found, both at the beginning and end of the intervention (Person
      Correlation = 0.846 and 0.903, respectively). High dependency measures by linear
      regression (R2= 0.715 and 0.816, respectively) were observed. CONCLUSION: A
      significant relation between HDL-C and ApoA1 was proven. Taking into account the
      importance that HDL-C levels seem to have on cardiovascular health, ApoA1 is
      presented as an important clinical marker to improve heart function as well as to
      reduce cardiovascular risk.

PMID- 25561148
TI  - Predictors of hyperlipidemia during the first half of pregnancy in Mexican women.
AB  - OBJECTIVE: To determine the predictors of hypercholesterolemia and of
      hypertriglyceridemia during the first half of pregnancy in Mexican women.
      METHODS: Cross-sectional comparative study of pregnant women with less than 21
      weeks of gestational age. MEASUREMENTS: Demographic information, obstetric
      history, prepregnancy body mass index, cholesterol and triglycerides. Cross
      tabulations and multiple logistic regression were used for statistical analysis.
      RESULTS: 230 participants; 61 women with normal prepregnancy body mass index, 108
      with overweight, and 61 with obesity. Dyslipidemia was defined as elevated
      cholesterol (>180 mg/dL) or triglycerides (>170 mg/dL). After adjusting by
      potential confounders, independent predictors of hypercholesterolemia included
      being overweight (OR=2.8, 95% CI 1.4-5.9), being obese (OR=3.7 95% CI 1.6-8.4) or
      being on the second trimester of pregnancy. The same predictors were found for
      hypertriglyceridemia, respectively OR=2.8, 95% CI 1.4-5.6, OR=2.9, 95% CI 1.3
      6.5, OR=2.6, 95% CI 1.4-4.7. CONCLUSION: Mexican women with prepregnancy
      overweight or obesity have greater risk of suffering hypercholesterolemia and
      hypertriglyceridemia during pregnancy. Women in the second trimester had higher
      levels of both lipids as compared to the first one. This is the first Mexican
      study that confirms the increase of lipids as gestational age progresses.

PMID- 25561149
TI  - An exclusively based parenteral fish-oil emulsion reverses cholestasis.
AB  - Prolonged parenteral nutrition (PN) leads to liver damage. Recent interest has
      focused on the lipid component of PN. A lipid emulsion based on w-3 fatty acids
      decrease conjugated bilirubin. A mixed lipid emulsion derived from soybean,
      coconut, olive, and fish oils reverses jaundice. Here we report the reversal of
      cholestasis and the improvement of enteral feeding tolerance in 1 infant with
      intestinal failure-associated liver disease. Treatment involved the substitution
      of a mixed lipid emulsion with one containing primarily omega-3 fatty acids
      during 37 days. Growth and biochemical tests of liver function improved
      significantly. This suggests that fat emulsions made from fish oils may be more
      effective means of treating this condition compared with an intravenous lipid
      emulsion containing soybean oil, medium -chain triglycerides, olive oil, and fish
      oil. 

PMID- 25561150
TI  - [Conditioning factors of weight condition].
AB  - INTRODUCTION: Epidemiological studies show that during the last two decades
      childhood obesity has increased dramatically to become, one of the major public
      health concerns. Dietary habits, lack of physical activity and the degree of
      obesity rates and worsen over the years making overweight children overweight
      adults. AIM: determine the influence of various modifiable factors (dietary
      habits, physical activity, inactivity and sleep) on the weight status of a group
      of school children. METHOD: An observational retrospective cross section of 129
      students of Madrid between 6 and 12 years with anthropometric data (weight,
      height and waist circumference), dietary (Kidmed), physical activity was
      performed (IPAQ adapted), inactivity and sleep. RESULTS: The most significant
      result was the excess weight of the children (28.1%), although these results are
      not statistically significant on any of the factors studied. Physical activity
      factor and time spent in sedentary activities by gender, in both cases lower
      values in girls than in boys with statistically significant differences (p <0.05)
      were observed. CONCLUSION: With the analyze of data, the factors studied versus
      weight status, no significant differences were found between the groups
      established by what has not been possible to define the influence thereof on
      weight status. We suggest the possible influence of genetic and environmental
      factors on the sample, beyond the established habits.

PMID- 25561151
TI  - Patient-generated subjective global assessment and classic anthropometry:
      comparison between the methods in detection of malnutrition among elderly with
      cancer.
AB  - INTRODUCTION: A comparative study of the various methods of nutritional
      assessment currently available in oncology are necessary to identify the most
      appropriate one, as well as the relationships that exist among the different
      instruments. OBJECTIVE: To compare the nutritional diagnosis obtained by the
      Patient-Generated Subjective Global Assessment (PG-SGA) with the objective
      anthropometric measurements in the elderly undergoing oncology treatment and to
      assess the concordance between the methods used in detecting malnutrition.
      METHODS: A cross-sectional study of the elderly, older than or equal to 60 years
      in age undergoing oncology treatment. The PG-SGA was performed and the
      anthropometric parameters including weight, height, Body Mass Index (BMI), arm
      circumference, arm muscle circumference, corrected arm muscle area, arm fat area,
      calf circumference, waist circumference, hip circumference, waist-hip ratio and
      triceps skinfold were evaluated. From a 24-hour recall the energy and
      macronutrient intakes were estimated. RESULTS: A total of 96 elderly patients
      were evaluated. The PG-SGA identified 29.2% with moderate malnutrition or
      suspected malnutrition and 14.6% with severe malnutrition. From among the elderly
      evaluated, 47.9% required critical nutritional intervention. The anthropometric
      parameters and the consumption of energy and macronutrients revealed significant
      differences based on the subjective PG-SGA classification. The prevalence of
      malnutrition ranged from 43.8% to 61.4%, depending upon the instrument used. The
      method most consistent with the diagnosis of malnutrition provided by the PGSGA
      was the BMI (kappa = 0.54; CI: 0.347-0.648). CONCLUSIONS: The PG-SGA showed a
      significant correlation with the anthropometric measurements and with food
      consumption for both the categorical classification, as well as for the scoring
      system. Diagnosis of malnutrition showed variable prevalence depending upon the
      method used, and none were found equivalent to the PG-SGA.

PMID- 25561152
TI  - Adequacy of energy and nutrient intake in patients with heart failure.
AB  - BACKGROUND: Nutritional factors have a significant influence on the prognosis of
      patients with heart failure (HF). OBJECTIVE: The goal of the present study was to
      assess the food intake of stable patients with HF. METHODS: Patients of both
      genders aged over 18 years with a confirmed diagnosis of HF were recruited and
      matched with healthy individuals for age, sex and BMI. Food records and weighing
      were used to assess participant nutritional intake. DRIs and NCEP-ATP III
      recommendations were used to evaluate the adequacy of nutritional intake.
      RESULTS: Sixty-five percent of the 40 patients in the sample and 48% of the 25
      control subjects were men. The mean age in both groups was 54+/-8 years and mean
      BMI was categorized as overweight. Carbohydrate, trans fatty acid and sodium
      intake were higher in the HF group as compared to control subjects (p=0.006, p.

PMID- 25561155
TI  - Administration of the nonsteroidal anti-inflammatory drug tolfenamic acid at
      embryo transfer improves maintenance of pregnancy and embryo survival in
      recipient mice.
AB  - PURPOSE: To evaluate the effect of the nonsteroidal anti-inflammatory drugs
      tolfenamic acid and flunixin meglumine in pregnancy rate and embryo survival of
      recipient mice subjected to embryo transfer. METHODS: A total of 142 recipient
      females were transferred with 2,931 embryos and treated with a single injection
      of tolfenamic acid (1 mg/kg; n = 54 females with 1,129 embryos), flunixin
      meglumine (2.5 mg/kg; n = 46 females with 942 embryos), or bi-distilled water (10
      mL/kg) as control group (n = 42 females with 860 embryos). Pregnancy was checked
      2 weeks after embryo transfer, delivery was registered on the due date, and
      litter size was recorded on Day 7 after birth. RESULTS: Pregnancy rate of
      tolfenamic acid treated females was significantly higher than flunixin group (P <
      0.05) and showed a tendency to be higher when compared to the control group (P =
      0.06). The number of pups born from transferred embryos in pregnant females was
      significantly higher for both treatment groups compared to controls (P < 0.05).
      Number of pups from total transferred embryos was higher for both treatment
      groups (P < 0.05) when compared to controls. CONCLUSION: The use of tolfenamic
      acid at the time of embryo transfer improves both pregnancy rate and number of
      live pups in recipient mice, with optimal effects observed with flunixin
      meglumine. We suggest that the use of tolfenamic acid has beneficial effects on
      the maintenance of pregnancy and embryo survival in recipient mice, which should
      be taken into account for further studies in other mammalian females.

PMID- 25561156
TI  - A comparison of pregnancy outcomes between day 3 and day 5/6 embryo transfers:
      does day of embryo transfer really make a difference?
AB  - PURPOSE: To determine if day of embryo transfer (ET) affects gestational age (GA)
      and/or birth weight (BW) at a single university fertility center that primarily
      performs day 5/6 ET. METHODS: Retrospective cohort study of 2392 singleton live
      births resulting from IVF/ICSI at a single large university fertility center from
      2003 to 2012. Patients were stratified by day 3 or day 5/6 ET. Outcome variables
      included patient age, gravidity, prior miscarriages, prior assisted reproduction
      technology cycles, number of embryos transferred, number of single ET,
      infertility diagnosis, neonatal sex, GA at birth, and BW. Subanalyses were
      performed on subgroups of preterm infants. A comparison was made between the
      study data and the Society of Assisted Reproductive Technologies (SART) published
      data. RESULTS: There was no difference in GA at birth (39 +/- 2.1 weeks for day 3
      ET, 39 +/- 1.9 weeks for day 5/6 ET) or BW between ET groups (3308 +/- 568 g for
      day 3 ET, 3268 +/- 543 g for day 5/6 ET). There was also no difference in the
      number of preterm deliveries (8.5 % for day 3 ET vs. 10.8 % for day 5/6 ET). The
      day 5/6 ET study data had significantly fewer pre-term deliveries than the SART
      day 5/6 ET data. CONCLUSION: In contrast to published SART data, GA and BW were
      not influenced by day of ET. Data may be more uniform at a single institution.
      Day 5/6 ET continues to offer improved pregnancy rates without compromising birth
      outcomes.

PMID- 25561157
TI  - Karyomapping-a comprehensive means of simultaneous monogenic and cytogenetic PGD:
      comparison with standard approaches in real time for Marfan syndrome.

PMID- 25561158
TI  - Downregulation of gene expression and activity of GRIM-19 affects mouse oocyte
      viability, maturation, embryo development and implantation.
AB  - PURPOSE: To investigate the expression of GRIM-19 (Gene associated with retinoid
      interferon-induced mortality 19) in mouse oocytes and preimplantation embryos,
      and to study the effect of GRIM-19 on the developmental competence of mouse
      oocytes and embryos. METHODS: GRIM-19 was evaluated at both mRNA and protein
      levels. The expression of GRIM-19 gene was downregulated in mouse oocytes
      cultured in vitro by specific small interfering RNA (siRNA) injection, while the
      activity of GRIM-19 was decreased by microinjection of a GRIM-19 antibody into
      the cytoplasm of germinal vesicle (GV) oocytes. Oocytes matured in vitro were
      then fertilized by intracytoplasmic sperm injection (ICSI), followed by
      observation and evaluation of fertilization rate, cleavage rate, blastocyst
      formation rate and implantation rate. RESULTS: GRIM-19 is expressed throughout
      oocyte maturation and preimplantation embryo development stages. GRIM-19 was
      localized primarily in the cytoplasm of all cells examined. Downregulation of
      gene expression and activity of GRIM-19 resulted in decreased oocyte viability,
      potency of oocyte maturation, embryo development and implantation. CONCLUSIONS:
      GRIM-19 may play important roles in mouse oogenesis and early embryonic
      development and implantation.

PMID- 25561159
TI  - Trends, fads and ART!
AB  - Morphological selection techniques of gametes and embryos are of current interest
      to clinical practice in ART. Although intracytoplasmic morphologically selected
      sperm injection (IMSI), time lapse imaging morphometry (TLIM) or quantification
      of chromosome numbers (PGS) are potentially useful in research, they have not
      been shown to be of statistically predictive value and, thus, have only limited
      clinical usefulness. We make the point that morphological markers alone cannot
      predict the success of the early embryo, which depends on the correct
      orchestration of a myriad of physiological and biochemical activation events that
      progress independently of the maternal or zygotic genome. Since previous attempts
      to identify metabolic markers for embryo quality have failed and there is no
      evidence that the intrinsic nature of gametes and embryos can be improved in the
      laboratory, embryologists can only minimize environmental or operator induced
      damage while these cells are manipulated ex vivo. 

PMID- 25561161
TI  - Cyclization cascades via N-amidyl radicals toward highly functionalized
      heterocyclic scaffolds.
AB  - The addition of a variety of radicals to the double bond of N
      (arylsulfonyl)acrylamides can trigger cyclization/aryl migration/desulfonylation
      cascades via amidyl radical intermediates 2. Herein, we demonstrate the synthetic
      utility of these intermediates in subsequent C-C and C-X bond-forming events to
      rapidly build up molecular complexity. First, we describe a regioselective one
      pot synthesis of CF3-, SCF3-, Ph2(O)P-, and N3-containing indolo[2,1
      a]isoquinolin-6(5H)-ones from N-[(2-ethynyl)arylsulfonyl]acrylamides through a
      multi-step radical reaction cascade. The process involves the one-pot formation
      of four new bonds (one C-X, two C-C, and one C-N), a formal 1,4-aryl migration,
      and desulfonylation of the starting material. Second, we present a one-pot
      synthesis of 3,3-disubstituted-2-dihydropyridinones from N
      (arylsulfonyl)acrylamides and 1,3-dicarbonyl compounds. In this case, a silver
      catalyzed radical cascade process involving the sequential formation of two new C
      C bonds and one C-N bond, a formal 1,4-aryl migration, and desulfonylation of the
      starting material explains the regioselective formation of densely functionalized
      heterocycles in a straightforward manner. Control experiments have unraveled the
      key intermediates as well as the sequence of individual steps involved in these
      transformations. 

PMID- 25561160
TI  - Sm16, a major component of Schistosoma mansoni cercarial excretory/secretory
      products, prevents macrophage classical activation and delays antigen processing.
AB  - BACKGROUND: Schistosoma mansoni cercariae penetrate the skin by releasing
      excretory/secretory (E/S) products known as 0-3hRP, which are associated with
      immune modulation through Toll like receptor (TLR) signalling. Furthermore, these
      secretions contain Sm16, which when given to cells as a recombinant protein
      inhibits human monocyte derived cytokine responses to TLR4 and TLR3 ligands.
      Nonetheless, the extent and mechanism(s) of these inhibitory effects remain
      largely uncharacterized. METHODS: Murine bone marrow derived macrophages were
      exposed to different fractions of 0-3hRP, obtained via ultracentrifugation, or
      recombinant Sm16. These cells were exposed to the parasite molecules in
      combination with different TLR ligands, or Interferon gamma, and tested for the
      production of the cytokines IL-10 and IL-12p40, and their ability to process
      antigen. RESULTS: The immunomodulatory function of 0-3hRP is enriched
      predominantly in the pellet fraction, which contains a greater proportion of
      Sm16, also corroborating the ability of recombinant Sm16 to inhibit macrophage
      activation in response to TLR ligands. We further demonstrate that Sm16 blocks
      classical activation of macrophages to LPS or IFN-gamma stimulation in vitro, and
      that inhibition of macrophage classical activation is independent of TLR2
      recognition. Finally we show that Sm16 shares the altered intracellular
      processing observed for 0-3hRP, and is able to delay antigen processing by
      macrophages. CONCLUSIONS: Collectively, our findings show that Sm16 is a major
      component of S. mansoni cercarial E/S products, and is partly responsible for its
      immune-regulatory properties. Moreover, we propose that the mechanism employed by
      Sm16 to exert its inhibitory function is likely to be linked with alteration of
      endosomal trafficking and is not dependent on particular TLR receptors. Finally,
      we suggest that accumulation of Sm16 in the skin after percutaneous infection
      with S. mansoni cercariae could contribute to limiting dermal inflammation.

PMID- 25561162
TI  - microRNA evolution and expression analysis in polyploidized cotton genome.
AB  - Cotton (Gossypium hirsutum L.), the most important fibre plant in the world, is a
      tetraploid species, originating from the reunion of two ancestral cotton species
      ~1-2 million years ago. It has been reported that a great number of genes were
      quickly erased or preferentially remained after whole-genome duplication,
      ultimately leading to morphogenesis evolution. However, microRNAs (miRNAs), a new
      class of gene regulators, have not been well studied in polyploidization. Here,
      we systematically investigated miRNA evolution amongst cultivated upland cotton
      G. hirsutum (AADD) and its two ancestors, G. arboreum (AA) and G. raimondii (DD).
      Our results show that certain highly conserved miRNAs were likely to be lost,
      whereas certain were remained after genome polyploidization. Cotton-specific
      miRNAs might undergo remarkably expansion, resulting in overall miRNA increase in
      upland cotton. Based on the sequenced genomes of G. arboreum and G. raimondii, we
      are capable for the first time to categorize the origin of miRNAs and coding
      genes in upland cotton. Different genome-derived miRNAs and miRNA*s displayed
      asymmetric expression pattern, implicating their diverse functions in upland
      cotton. No miRNA targeting preference was observed between different genome
      derived miRNAs. The origin of miRNAs and coding genes has no impact on becoming
      miRNAs and their targets, despite some miRNAs and their targets are extremely
      conserved in the three cotton species. GO- and KEGG-based analysis of conserved
      miRNAs show that conserved miRNAs and their targets participate in a series of
      important biological processes and metabolism pathways. Additionally, A-derived
      miRNAs might be more responsible for ovule and fibre development. 

PMID- 25561164
TI  - Interhemispheric inhibition of corticospinal projections to forearm muscles.
AB  - OBJECTIVE: Interhemispheric inhibition (IHI) is typically examined via responses
      elicited in intrinsic hand muscles. As the cortical representations of proximal
      and distal muscles in the upper limb are distinguished in terms of their inter
      hemispheric projections, we sought to determine whether the IHI parameters
      established for the hand apply more generally. METHODS: We investigated IHI at 5
      different conditioning stimulus (CS) intensities and a range of short-latency
      inter-stimulus intervals (ISIs) in healthy participants. Conditioning and test
      stimuli were delivered over the M1 representation of the right and left flexor
      carpi radialis respectively. RESULTS: IHI increased as a function of CS
      intensity, and was present for ISIs between 7 and 15ms. Inhibition was most
      pronounced for the 10ms ISI at all CS intensities. CONCLUSIONS: The range of
      parameters for which IHI is elicited in projections to the forearm is similar to
      that reported for the hand. The specific utility lies in delineation of stimulus
      parameters that permit both potentiation and attenuation of IHI to be assessed.
      SIGNIFICANCE: In light of evidence that there is a greater density of callosal
      projections between cortical areas that represent proximal muscles than between
      those corresponding to distal limb muscles, and in view of the assumption that
      variations in functional connectivity to which such differences give rise may
      have important implications for motor behavior, it is critical to determine
      whether processes mediating the expression of IHI depend on the effector that is
      studied. This issue is of further broad significance given the practical utility
      of movements generated by muscles proximal to the wrist in the context of upper
      limb rehabilitation.

PMID- 25561163
TI  - Combing of genomic DNA from droplets containing picograms of material.
AB  - Deposition of linear DNA molecules is a critical step in many single-molecule
      genomic approaches including DNA mapping, fiber-FISH, and several emerging
      sequencing technologies. In the ideal situation, the DNA that is deposited for
      these experiments is absolutely linear and uniformly stretched, thereby enabling
      accurate distance measurements. However, this is rarely the case, and
      furthermore, current approaches for the capture and linearization of DNA on a
      surface tend to require complex surface preparation and large amounts of starting
      material to achieve genomic-scale mapping. This makes them technically demanding
      and prevents their application in emerging fields of genomics, such as single
      cell based analyses. Here we describe a simple and extremely efficient approach
      to the deposition and linearization of genomic DNA molecules. We employ droplets
      containing as little as tens of picograms of material and simply drag them, using
      a pipet tip, over a polymer-coated coverslip. In this report we highlight one
      particular polymer, Zeonex, which is remarkably efficient at capturing DNA. We
      characterize the method of DNA capture on the Zeonex surface and find that the
      use of droplets greatly facilitates the efficient deposition of DNA. This is the
      result of a circulating flow in the droplet that maintains a high DNA
      concentration at the interface of the surface/solution. Overall, our approach
      provides an accessible route to the study of genomic structural variation from
      samples containing no more than a handful of cells. 

PMID- 25561166
TI  - The need for higher-order averaging in the stability analysis of hovering,
      flapping-wing flight.
AB  - Because of the relatively high flapping frequency associated with hovering
      insects and flapping wing micro-air vehicles (FWMAVs), dynamic stability analysis
      typically involves direct averaging of the time-periodic dynamics over a flapping
      cycle. However, direct application of the averaging theorem may lead to false
      conclusions about the dynamics and stability of hovering insects and FWMAVs.
      Higher-order averaging techniques may be needed to understand the dynamics of
      flapping wing flight and to analyze its stability. We use second-order averaging
      to analyze the hovering dynamics of five insects in response to high-amplitude,
      high-frequency, periodic wing motion. We discuss the applicability of direct
      averaging versus second-order averaging for these insects. 

PMID- 25561167
TI  - CXCL10 induces the recruitment of monocyte-derived macrophages into kidney, which
      aggravate puromycin aminonucleoside nephrosis.
AB  - The mechanism responsible for trafficking of monocyte-derived macrophages into
      kidney in the puromycin aminonucleoside model of nephrotic syndrome in rats (PAN
      NS), and the significance of this infiltration, remain largely unknown. CXCL10, a
      chemokine secreted in many T helper type 1 (Th1) inflammatory diseases, exhibits
      important roles in trafficking of monocytes and activated T cells. We
      hypothesized that induction of circulating interferon (IFN)-gamma and glomerular
      tumour necrosis factor (TNF)-alpha during PAN-NS would stimulate the release of
      CXCL10 by podocytes, leading to infiltration of activated immune cells and
      greater glomerular injury. We found that serum IFN-gamma, glomerular Cxcl10 mRNA
      and intra- and peri-glomerular macrophage infiltration were induced strongly
      during the late acute phase of PAN-NS in Wistar rats, but not in nude
      (Foxn1(rnu/rnu) ) rats lacking functional effector T lymphocytes. Wistar rats
      also developed significantly greater proteinuria than nude rats, which could be
      abolished by macrophage depletion. Stimulation of cultured podocytes with both
      IFN-gamma and TNF-alpha markedly induced the expression of Cxcl10 mRNA and CXCL10
      secretion. Together, these data support our hypothesis that increased circulating
      IFN-gamma and glomerular TNF-alpha induce synergistically the production and
      secretion of CXCL10 by podocytes, attracting activated macrophages into kidney
      tissue. The study also suggests that IFN-gamma, secreted from Th1 lymphocytes,
      may prime proinflammatory macrophages that consequently aggravate renal injury. 

PMID- 25561169
TI  - Structural insights into stereospecific reduction of alpha, beta-unsaturated
      carbonyl substrates by old yellow enzyme from Gluconobacter oxydans.
AB  - We report the crystal structure of old yellow enzyme (OYE) family protein Gox0502
      (a.a 1-315) in free form at 3.3 A. Detailed structural analysis revealed the key
      residues involved in stereospecific determination of Gox0502, such as Trp66 and
      Trp100. Structure-based computational analysis suggested the bulky side chains of
      these tryptophan residues may play important roles in product stereoselectivity.
      The introduction of Ile or Phe or Tyr mutation significantly reduced the product
      diastereoselectivity. We hypothesized that less bulky side chains at these
      critical residues could create additional free space to accommodate intermediates
      with different conformations. Notably, the introduction of Phe mutation at
      residue Trp100 increased catalytic activity compared to wild-type Gox0502 toward
      a set of substrates tested, which suggests that a less bulky Phe side chain at
      residue W100F may facilitate product release. Therefore, Gox0502 structure could
      provide useful information to generate desirable OYEs suitable for
      biotechnological applications in industry. 

PMID- 25561168
TI  - Infective endocarditis in patients with an implanted transcatheter aortic valve:
      Clinical characteristics and outcome of a new entity.
AB  - AIMS: This study reports one case and review the literature on TAVI-associated
      endocarditis (TAVIE), to describe its clinical picture and to perform an analysis
      on prognostic factors. METHODS AND RESULTS: A MEDLINE search from January 2002 to
      October 2014 revealed 31 cases of TAVIE, including 1 from our hospital. Median
      age was 81 years (IQR, 78-85), 53% of patients were males and the median age
      adjusted Charlson score was 7 (IQR, 5-8). Heart failure was recorded in 42%,
      embolic events in 19%, and periannular complications in 45%. The most common
      causative agent was Enterococcus spp (36%). Ten patients (32%) underwent surgery
      and nine patients died (29%). The prognostic factors for 6-month mortality were
      heart failure (HR, 9.97 [3.7-24.5]; p = 0.001), periannular complications (HR,
      11.82 [3.3-41.3]; p = 0.004), and nonenterococcal/streptococcal etiology (HR,
      4.76 [2.1-11.1]; p = 0.03). In patients with heart failure who did not undergo
      surgery, mortality was 89% (8 out of 9); in those who did undergo surgery,
      mortality was 0% (p < 0.001). CONCLUSIONS: TAVIE is an emerging entity with high
      mortality. Patients with heart failure who did not undergo surgery had a higher
      probability of dying. Surgical treatment provided better outcomes even in
      patients in whom surgery had previously been ruled out.

PMID- 25561170
TI  - Predators indirectly reduce the prevalence of an insect-vectored plant pathogen
      independent of predator diversity.
AB  - A widely cited benefit of predator diversity is greater suppression of insect
      herbivores, with corresponding increases in plant biomass. In the context of a
      vector-borne pathogen system, predator species richness may also influence plant
      disease risk via the direct effects of predators on the abundance and behavior of
      herbivores that also act as pathogen vectors. Using an assemblage of generalist
      insect predators, we examined the relationship between predator species richness
      and the prevalence of the aphid-vectored cereal yellow dwarf virus in wheat. We
      found that increasing predator richness enhanced suppression of the vector
      population and that pathogen prevalence was reduced when predators were present,
      but the reduction in prevalence was independent of predator species richness. To
      determine the mechanism(s) by which predator species richness contributes to
      vector suppression, but not pathogen prevalence, we evaluated vector movement and
      host plant occupancy in response to predator treatments. We found that pathogen
      prevalence was unrelated to vector suppression because host plant occupancy by
      vectors did not vary as a function of vector abundance. However, the presence of
      predators reduced pathogen prevalence because predators stimulated greater plant
      to-plant movement by vectors, which likely diminished vector feeding time and
      reduced the transmission efficiency of this persistent pathogen. We conclude that
      community structure (i.e., the presence of predators), but not predator
      diversity, is a potential factor influencing local plant infection by this insect
      vectored pathogen. 

PMID- 25561171
TI  - Assessing the impact of fire on the spatial distribution of Larrea tridentata in
      the Sonoran Desert, USA.
AB  - In southwestern American deserts, fire has been historically uncommon because of
      insufficient continuity of fuel for spreading. However, deserts have been invaded
      by exotic species that now connect the empty space between shrubs to carry fire.
      We hypothesized that fire would change the spatial distribution of surviving
      Larrea tridentata shrubs. We established two study plots, one each in a burned
      and unburned area, and recorded location and living status of all shrubs. We
      performed univariate and bivariate point pattern analyses to characterize the
      impact of fire on the overall distribution of shrubs. Additionally, we used a
      simple wildfire model to determine how close we could come to reconstructing the
      observed spatial pattern of living and dead shrubs. We found a hyper-dispersed
      pattern of shrubs at finer scales and a random pattern at broader scales for both
      the unburned plot and for the living and dead shrubs combined in the burned plot,
      the latter providing an approximation of the pre-burn distribution of shrubs.
      After fire, living shrubs showed a clustered pattern at scales >2.5 m, whereas
      dead shrubs were randomly distributed, indicating that fire caused a change in
      the spatial pattern of the surviving shrubs. The fire model was able to partially
      reconstruct the spatial pattern of Larrea, but created a more clustered
      distribution for both living and dead shrubs. Our study reinforces the key role
      of fire in altering landscapes that had not been habituated to fire, and suggests
      the existence of potential cascading effects across the entire plant community.

PMID- 25561172
TI  - Antibiotics: An irresistible newcomer.

PMID- 25561173
TI  - Optogenetic control of organelle transport and positioning.
AB  - Proper positioning of organelles by cytoskeleton-based motor proteins underlies
      cellular events such as signalling, polarization and growth. For many organelles,
      however, the precise connection between position and function has remained
      unclear, because strategies to control intracellular organelle positioning with
      spatiotemporal precision are lacking. Here we establish optical control of
      intracellular transport by using light-sensitive heterodimerization to recruit
      specific cytoskeletal motor proteins (kinesin, dynein or myosin) to selected
      cargoes. We demonstrate that the motility of peroxisomes, recycling endosomes and
      mitochondria can be locally and repeatedly induced or stopped, allowing rapid
      organelle repositioning. We applied this approach in primary rat hippocampal
      neurons to test how local positioning of recycling endosomes contributes to axon
      outgrowth and found that dynein-driven removal of endosomes from axonal growth
      cones reversibly suppressed axon growth, whereas kinesin-driven endosome
      enrichment enhanced growth. Our strategy for optogenetic control of organelle
      positioning will be widely applicable to explore site-specific organelle
      functions in different model systems. 

PMID- 25561174
TI  - HIV: Seeking ultimate victory.

PMID- 25561176
TI  - A possible close supermassive black-hole binary in a quasar with optical
      periodicity.
AB  - Quasars have long been known to be variable sources at all wavelengths. Their
      optical variability is stochastic and can be due to a variety of physical
      mechanisms; it is also well-described statistically in terms of a damped random
      walk model. The recent availability of large collections of astronomical time
      series of flux measurements (light curves) offers new data sets for a systematic
      exploration of quasar variability. Here we report the detection of a strong,
      smooth periodic signal in the optical variability of the quasar PG 1302-102 with
      a mean observed period of 1,884 +/- 88 days. It was identified in a search for
      periodic variability in a data set of light curves for 247,000 known,
      spectroscopically confirmed quasars with a temporal baseline of about 9 years.
      Although the interpretation of this phenomenon is still uncertain, the most
      plausible mechanisms involve a binary system of two supermassive black holes with
      a subparsec separation. Such systems are an expected consequence of galaxy
      mergers and can provide important constraints on models of galaxy formation and
      evolution. 

PMID- 25561175
TI  - SLC38A9 is a component of the lysosomal amino acid sensing machinery that
      controls mTORC1.
AB  - Cell growth and proliferation are tightly linked to nutrient availability. The
      mechanistic target of rapamycin complex 1 (mTORC1) integrates the presence of
      growth factors, energy levels, glucose and amino acids to modulate metabolic
      status and cellular responses. mTORC1 is activated at the surface of lysosomes by
      the RAG GTPases and the Ragulator complex through a not fully understood
      mechanism monitoring amino acid availability in the lysosomal lumen and involving
      the vacuolar H(+)-ATPase. Here we describe the uncharacterized human member 9 of
      the solute carrier family 38 (SLC38A9) as a lysosomal membrane-resident protein
      competent in amino acid transport. Extensive functional proteomic analysis
      established SLC38A9 as an integral part of the Ragulator-RAG GTPases machinery.
      Gain of SLC38A9 function rendered cells resistant to amino acid withdrawal,
      whereas loss of SLC38A9 expression impaired amino-acid-induced mTORC1 activation.
      Thus SLC38A9 is a physical and functional component of the amino acid sensing
      machinery that controls the activation of mTOR. 

PMID- 25561177
TI  - Compositional engineering of perovskite materials for high-performance solar
      cells.
AB  - Of the many materials and methodologies aimed at producing low-cost, efficient
      photovoltaic cells, inorganic-organic lead halide perovskite materials appear
      particularly promising for next-generation solar devices owing to their high
      power conversion efficiency. The highest efficiencies reported for perovskite
      solar cells so far have been obtained mainly with methylammonium lead halide
      materials. Here we combine the promising-owing to its comparatively narrow
      bandgap-but relatively unstable formamidinium lead iodide (FAPbI3) with
      methylammonium lead bromide (MAPbBr3) as the light-harvesting unit in a bilayer
      solar-cell architecture. We investigated phase stability, morphology of the
      perovskite layer, hysteresis in current-voltage characteristics, and overall
      performance as a function of chemical composition. Our results show that
      incorporation of MAPbBr3 into FAPbI3 stabilizes the perovskite phase of FAPbI3
      and improves the power conversion efficiency of the solar cell to more than 18
      per cent under a standard illumination of 100 milliwatts per square centimetre.
      These findings further emphasize the versatility and performance potential of
      inorganic-organic lead halide perovskite materials for photovoltaic applications.

PMID- 25561179
TI  - Cell biology: Organelles under light control.

PMID- 25561178
TI  - A new antibiotic kills pathogens without detectable resistance.
AB  - Antibiotic resistance is spreading faster than the introduction of new compounds
      into clinical practice, causing a public health crisis. Most antibiotics were
      produced by screening soil microorganisms, but this limited resource of
      cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce
      antibiotics have been unable to replace this platform. Uncultured bacteria make
      up approximately 99% of all species in external environments, and are an untapped
      source of new antibiotics. We developed several methods to grow uncultured
      organisms by cultivation in situ or by using specific growth factors. Here we
      report a new antibiotic that we term teixobactin, discovered in a screen of
      uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a
      highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III
      (precursor of cell wall teichoic acid). We did not obtain any mutants of
      Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The
      properties of this compound suggest a path towards developing antibiotics that
      are likely to avoid development of resistance.

PMID- 25561182
TI  - [Cardiovascular disease in patients with type 1 and type 2 diabetes in Spain].
AB  - BACKGROUND AND OBJECTIVE: To describe the prevalence of cardiovascular disease
      (CVD) in type 1 diabetes (T1DM) and to compare it with that observed in type 2
      diabetes (T2DM) and normal population in Spain. PATIENTS AND METHODS: Cross
      sectional study (18-70 years-old). Information on CVD was available from a nurse
      administered questionnaire (Di@bet.es Study, NORMAL=3,430, T2DM=312) and from a
      physician reporting form (T1DM=1,382). Differences in the crude and adjusted
      prevalence of coronary heart (CHD), cerebrovascular (CNSD), peripheral vascular
      (PVD) and overall CV (CVD) disease were investigated between T1DM vs. NORMAL, and
      T1DM vs. T2DM groups. RESULTS: We found differences in age, body mass index,
      proportion of women, dyslipemia and antihypertensive medication between T1DM vs.
      NORMAL and T1DM vs. T2DM (all P<.001). Smoking prevalence was not different
      between T1DM vs. T2DM and it was lower in T1DM compared to NORMAL (P<.0001). The
      percentage of CHD, CNSD, PVD, and overall CVD in T1DM vs. NORMAL was 3.0 vs. 2.5
      (P=.31), 0.70 vs. 1.10 (P=.22), 2.61 vs. 0.20 (P<.0001), and 5.1 vs. 3.44
      (P<.01), respectively. The prevalence in T2DM (vs. T1DM) was 11.3 (P<.0001), 3.5
      (P<.0001), 4.2 (P=.13), and 17% (P<.0001), respectively. Multiple logistic
      regression adjusted models showed a higher prevalence of CHD (odds ratio [OR]
      2.27, 95% confidence interval [95% CI] 1.41-3.67), PVD (OR 15.35, 95% CI 5.61
      42.04), and overall CVD (OR 2.32, 95% CI 1.55-3.46), but not for CNSD (OR 0.49,
      95% CI 0.19-1.27) in T1DM compared to NORMAL. No differences were found between
      T1DM and T2DM. CONCLUSIONS: We found a higher prevalence of CVD in a
      Mediterranean population of T1DM individuals compared with non-diabetic subjects.
      This prevalence was similar to that observed in T2DM.

PMID- 25561183
TI  - To pair or not to pair: Sources of social variability with white-faced saki
      monkeys (Pithecia pithecia) as a case study.
AB  - Intraspecific variability in social systems is gaining increased recognition in
      primatology. Many primate species display variability in pair-living social
      organizations through incorporating extra adults into the group. While numerous
      models exist to explain primate pair-living, our tools to assess how and why
      variation in this trait occurs are currently limited. Here I outline an approach
      which: (i) utilizes conceptual models to identify the selective forces driving
      pair-living; (ii) outlines novel possible causes for variability in social
      organization; and (iii) conducts a holistic species-level analysis of social
      behavior to determine the factors contributing to variation in pair-living. A
      case study on white-faced sakis (Pithecia pithecia) is used to exemplify this
      approach. This species lives in either male-female pairs or groups incorporating
      "extra" adult males and/or females. Various conceptual models of pair-living
      suggest that high same-sex aggression toward extra-group individuals is a key
      component of the white-faced saki social system. Variable pair-living in white
      faced sakis likely represents alternative strategies to achieve competency in
      this competition, in which animals experience conflicting selection pressures
      between achieving successful group defense and maintaining sole reproductive
      access to mates. Additionally, independent decisions by individuals may generate
      social variation by preventing other animals from adopting a social organization
      that maximizes fitness. White-faced saki inter-individual relationships and
      demographic patterns also lend conciliatory support to this conclusion. By
      utilizing both model-level and species-level approaches, with a consideration for
      potential sources of variation, researchers can gain insight into the factors
      generating variation in pair-living social organizations.

PMID- 25561180
TI  - Broad CTL response is required to clear latent HIV-1 due to dominance of escape
      mutations.
AB  - Despite antiretroviral therapy (ART), human immunodeficiency virus (HIV)-1
      persists in a stable latent reservoir, primarily in resting memory CD4(+) T
      cells. This reservoir presents a major barrier to the cure of HIV-1 infection. To
      purge the reservoir, pharmacological reactivation of latent HIV-1 has been
      proposed and tested both in vitro and in vivo. A key remaining question is
      whether virus-specific immune mechanisms, including cytotoxic T lymphocytes
      (CTLs), can clear infected cells in ART-treated patients after latency is
      reversed. Here we show that there is a striking all or none pattern for CTL
      escape mutations in HIV-1 Gag epitopes. Unless ART is started early, the vast
      majority (>98%) of latent viruses carry CTL escape mutations that render infected
      cells insensitive to CTLs directed at common epitopes. To solve this problem, we
      identified CTLs that could recognize epitopes from latent HIV-1 that were
      unmutated in every chronically infected patient tested. Upon stimulation, these
      CTLs eliminated target cells infected with autologous virus derived from the
      latent reservoir, both in vitro and in patient-derived humanized mice. The
      predominance of CTL-resistant viruses in the latent reservoir poses a major
      challenge to viral eradication. Our results demonstrate that chronically infected
      patients retain a broad-spectrum viral-specific CTL response and that appropriate
      boosting of this response may be required for the elimination of the latent
      reservoir. 

PMID- 25561181
TI  - [Clinical value of N-terminal pro-B-type natriuretic peptide measurement in the
      follow up of pulmonary vein ablation].
AB  - BACKGROUND AND OBJECTIVE: N-terminal pro-B-type natriuretic peptide (NT-proBNP)
      correlates with burden of arrhythmia in atrial fibrillation (AF) patients. Our
      objective is to validate the usefulness of the measurement of NT-pro-BNP to
      determine the success of AF ablation in a long term follow up. PATIENTS AND
      METHODS: Prospective observational study in which 75 patients with preserved
      systolic function (81% men; mean age (SD) 52 (9) years; 58.7% paroxysmal)
      underwent circumferential pulmonary vein isolation. Determination of NT-proBNP
      baseline and one year after the procedure was performed. The relation between NT
      proBNP levels and the success of the procedure is analyzed. RESULTS: In the
      follow up 53 (70.7%) patients remained free of recurrences. A>30% decrease of NT
      proBNP levels identified success with a sensitivity of 79.2%, specificity 81.8%,
      positive predictive value 91.3% and negative 62% (area under ROC curve 0.84, 95%
      confidence interval 73-95.6). This reduction was associated with a decrease in
      left atrial volume and pressure and the presence of diastolic dysfunction (all
      P<.05). CONCLUSIONS: The decrease of NT-proBNP levels in patients undergoing AF
      ablation is useful as a marker of success in the follow up and is associated with
      hemodynamic improvement.

PMID- 25561184
TI  - A successful case of Cushing's disease pregnancy treated with ketoconazole.
AB  - PURPOSE: The association of pregnancy and Cushing's disease (CD) is rare.
      Treatment of Cushing's syndrome (CS) is imperative to reduce maternal and fetal
      morbidity. Ketoconazole is a widely used drug for CS control when the woman is
      not pregnant but concerns about its teratogenicity and embryotoxicity restricted
      its use during pregnancy. METHODS AND RESULTS: We describe a case of a CD patient
      managed with Ketoconazole during the first and second trimester and other cares
      for her metabolic CS aspects during pregnancy. She delivered a normal female
      baby. CONCLUSIONS: It is supposed that even with treatment the relatively
      hypercortisolemic mother could protect her child from the embryotoxicity of
      ketoconazole as proved in rat fetuses and we suggest that ketoconazole could be
      an emergency pharmacological therapeutic option for CS management during
      pregnancy.

PMID- 25561185
TI  - Predicting early intrahepatic recurrence after curative resection of colorectal
      liver metastases with molecular markers.
AB  - BACKGROUND: The aim of this case-control study was to identify
      clinicopathological factors and test three relevant biomarkers for their ability
      to predict early intrahepatic recurrence after curative liver resection for
      colorectal liver metastases (CLM). METHODS: Of the 184 patients with CLM
      undergoing hepatectomy between January 2007 and December 2009, thirty patients
      had intrahepatic disease recurrence within 6 months. The control group was
      randomly selected from a cohort of patients between April 1997 and December 2005
      who have survived without disease recurrence after CLM resection for over 5
      years. Both groups were matched for size of metastasis greater than 5.0 cm, the
      presence of multiple metastases, and synchronous versus metachronous CLM. The
      final study population consisted of 60 patients with CLM undergoing R0
      hepatectomy, 30 of whom had early intrahepatic-only recurrences (study group) and
      30 patients without recurrence for more than 5 years (control group). Both groups
      were analyzed and compared for the presence of clinical factors and expression
      levels of CD133, survivin, and Bcl-2 within tumor tissue. RESULTS:
      Characteristics of patients were similar between the two groups except primary
      tumor location and administration of postoperative chemotherapy. Expression level
      of CD133 and survivin were significantly increased in tumors of patients with
      recurrence compared to patients without recurrence. On multivariate analysis high
      tumor expression levels of CD133 (odds ratio [OR] 14.7, confidence interval [CI]
      1.8-121.3, p = 0.012) and survivin (OR 9.5, CI 2.1-44.3, p = 0.004) and
      postoperative chemotherapy (OR 4.8, CI 1.01-22.9, p = 0.049) were independent
      factors associated with early intrahepatic recurrence. CONCLUSIONS: Tumor
      expression levels of CD133 and survivin may be a useful predictor of early
      intrahepatic recurrence after hepatectomy for CLM. Administration of
      postoperative chemotherapy may prevent early intrahepatic recurrence.

PMID- 25561186
TI  - Relationships between SMAD3 expression and preoperative fluoropyrimidine-based
      chemoradiotherapy response in locally advanced rectal cancer patients.
AB  - BACKGROUND: SMAD3, which is accumulated in the nucleus, transcriptionally
      regulates TGF-beta target genes, playing a significant role in mediating the
      activities of TGF-beta. In this study, we assessed the roles of TGF-beta1, SMAD3,
      and phosphorylated SMAD3 expressions in patients with locally advanced rectal
      cancer following preoperative fluoropyrimidine-based chemoradiotherapy. METHODS:
      Using immunohistochemistry, we examined TGF-beta1, SMAD3, and phosphorylated
      SMAD3 expressions in pre-chemoradiotherapy cancer tissues from 86 locally
      advanced rectal cancer patients. After chemoradiotherapy, 64 of 86 (74.4 %)
      locally advanced rectal cancer patients were classified as responders
      (pathological tumor regression grades of 2-4). RESULTS: A multivariate analysis
      showed that phosphorylated SMAD3 overexpression correlated to poor preoperative
      chemoradiotherapy responses (P = 0.015; OR 7.218; 95 % CI 1.479-35.229).
      Furthermore, a poor response (pathological tumor regression grades of 0-1) was an
      independent predictor of postoperative relapse (P = 0.021; OR 5.452; 95 % CI
      1.286-23.113). Additionally, patients with phosphorylated SMAD3 overexpression
      were found to have a worse disease-free survival (P = 0.023). CONCLUSIONS: Our
      data suggested that analyzing pre-chemoradiotherapy tumors for phosphorylated
      SMAD3 overexpression would assist physicians in identifying locally advanced
      rectal cancer patients who may have a poor response risk to preoperative
      fluoropyrimidine-based chemoradiotherapy.

PMID- 25561187
TI  - Long-term outcomes of open and video-assisted thoracoscopic lung lobectomy for
      the treatment of early stage non-small cell lung cancer are similar: a propensity
      matched study.
AB  - BACKGROUND: Generally, in retrospective studies, favourable short- and long-term
      outcomes for patients after lung lobectomy for early stage non-small cell lung
      cancer (NSCLC) using video-assisted thoracoscopic surgery (VATS) have been
      reported. However, the interpretation of lung lobectomy outcomes may be biased in
      retrospective settings. METHODS: We retrospectively reviewed patients who
      underwent lung lobectomy for cT1-2N0M0 NSCLC from 2001 to 2010. The outcomes of
      patients who underwent VATS lobectomy were compared to those who underwent open
      lobectomy before and after performing propensity score matching. Preoperative
      covariates were entered when developing the propensity score-matching model.
      RESULTS: This study reviewed the outcomes of 101 VATS patients and 184 open
      lobectomy patients. Before propensity score matching, the VATS group had a higher
      mean age (p < 0.0001), smaller solid tumour size (p = 0.0042), similar whole
      tumour size (p = 0.2082), and larger tumour-disappearance ratio (p = 0.0007). The
      VATS group had a shorter mean operation time (p = 0.0002), less blood loss (p <
      0.0001), shorter chest tube duration (p = 0.0002), and shorter hospital stay (p <
      0.0001). As for long-term outcomes, the VATS group had higher disease-free,
      disease-specific, and overall survival rates (p values by log-rank test: 0.0049,
      0.0154, and 0.032, respectively). After propensity score matching, all
      differences, except operation time, blood loss, chest tube duration, and hospital
      stay, were no longer significant. CONCLUSIONS: VATS lobectomy is less invasive
      than open lobectomy, but in terms of survival outcomes, VATS lobectomy was
      oncologically equivalent to open lobectomy. The oncological benefit of VATS
      reported by retrospective studies might be overestimated.

PMID- 25561188
TI  - Penetrating Cervical Trauma. "Current Concepts in Penetrating Trauma", IATSIC
      Symposium, International Surgical Society, Helsinki, Finland, August 25-29, 2013.
AB  - Patients with penetrating wounds to the neck present with overt symptoms and/or
      signs or are asymptomatic or modestly/moderately symptomatic. With overt symptoms
      and/or signs, immediate resuscitation and an emergency operation are appropriate.
      Asymptomatic patients or those with modest or moderate symptoms and/or signs
      undergo observation or a diagnostic evaluation to avoid the 45% "negative"
      exploration rate documented in the past (denominator = all patients).
      Asymptomatic patients with penetration of the platysma muscle, but no signs of a
      visceral or vascular injury, should undergo serial physical examinations every 6
      8 for 24-36 h before discharge. Noncontrast CT does not add to the accuracy of
      serial physical examinations. In stable patients with a variety of
      modest/moderate symptoms or signs possibly related to an injury to the carotid
      artery, CT-arteriography has become the diagnostic modality of choice. Patients
      with possible injuries to the cervical esophagus are often still evaluated with a
      Gastrografin swallow and, if needed, a "thin" barium swallow prior to fiberoptic
      esophagoscopy. CT-esophagograms are likely to replace these time-honored studies
      in the near future. Over 85% of patients with injuries to the trachea present
      with overt symptoms or signs, while the remainder have historically been
      evaluated with laryngoscopy and fiberoptic bronchoscopy. Again, cervical
      multislice CT is likely to replace these studies. Operative repair of the carotid
      artery with 6-0 polypropylene sutures requires heparinization and shunting on
      rare occasions. Both the trachea and esophagus are repaired with 3-0 absorbable
      sutures, and tracheostomy and esophageal diversion are used in only large and/or
      complex injuries. Sternal head or sternocleiodomastoid interposition flaps are
      used when combined visceral and vascular injuries are present.

PMID- 25561189
TI  - The impact of type of mesh repair on 2nd recurrence after recurrent groin hernia
      surgery.
AB  - BACKGROUND: According to the Swedish Hernia Register (SHR), the reoperation rate
      is more than doubled after recurrent groin hernia repair compared with primary
      repair. The aim was to study the impact of type of mesh repair used in recurrent
      groin hernia surgery on a 2nd recurrence in a population-based cohort derived
      from the SHR. MATERIAL AND METHOD: All 1st recurrent hernia repairs in the south
      west region of Sweden, registered in SHR between 1998 up to 2007 were included. A
      questionnaire was sent in 2009. Patients stating a new lump or persisting
      problems were examined. A 2nd recurrence was identified as a 2nd reoperation or
      at physical examination. The incidence was analysed comparing anterior mesh
      repair (AMR) and posterior mesh repairs (PMR) (endoscopic and open). RESULTS:
      Eight hundred and fifteen recurrent operations in 767 patents were analysed, 401
      AMRs and 414 PMRs. PMR had a lower 2nd recurrence rate compared with AMR (5.6 vs.
      11.0 %) (p = 0.025). An increased risk [3.21 (CI 1.33-7.44) (p = 0.009)] of a
      subsequent 2nd recurrence was seen after anterior index repair followed by AMR
      and a decreased risk [0.08 (CI 0.01-0.94) (p = 0.045)] after posterior index
      repair followed by AMR. CONCLUSION: PMR in recurrent groin hernia surgery was
      associated with a lower 2nd recurrence rate compared to anterior. A posterior
      approach for 1st recurrent operation is recommended after an anterior index
      repair and an anterior approach after a posterior index operation.

PMID- 25561190
TI  - Risk factors for incisional and organ space surgical site infections after liver
      resection are different.
AB  - BACKGROUND: Surgical site infection (SSI) is a common cause of major morbidity
      after liver resection. This study aimed to identify the risk factors for
      incisional and organ/space SSIs after liver resection. METHODS: Our liver surgery
      database was retrospectively analyzed for patients treated between January 2009
      and November 2012 in a tertiary care Swiss hospital. Univariate and multivariate
      analyses were conducted on preoperative, intraoperative, and postoperative
      variables to identify risk factors for incisional and organ/space SSIs. RESULTS:
      In a total of 226 patients, SSI incidences were 12.8 % (incisional), 4.0 %
      (organ/space), and 1.8 % (both). Univariate analysis showed that incisional SSIs
      were associated with high American Society of Anesthesiologists (ASA) scores,
      preoperative anemia, hypoalbuminemia, low prothrombin time, viral or alcoholic
      chronic hepatitis, liver cirrhosis, and prolonged operation times. Organ/space
      SSIs were associated with high rates of red blood cell transfusions, concomitant
      bowel surgery, and prolonged operation times. Multivariate analysis revealed that
      risk factors for incisional SSIs were anemia [odds ratio (OR) 2.82], high ASA
      scores (OR 2.88), presence of hepatitis or cirrhosis (OR 5.07), and prolonged
      operation times (OR 9.61). The only risk factor for organ/space SSIs was
      concomitant bowel surgery (OR 5.53). Hospital stays were similar in organ/space
      and incisional SSI groups, but significantly longer for those with both
      organ/space and incisional SSIs. CONCLUSIONS: High ASA scores, anemia, chronic
      hepatitis or liver cirrhosis, and prolonged operations increased the risk of
      incisional SSIs; concomitant bowel surgery increased the risk of organ/space SSI.
      Specific precautions to prevent organ/space and incisional SSIs may shorten
      hospital stays.

PMID- 25561191
TI  - Clinicopathological significance of mucin production in patients with papillary
      cholangiocarcinoma.
AB  - BACKGROUND: The clinicopathologic significance of mucin production in patients
      with papillary cholangiocarcinoma (PCC) is still controversial. We aimed at
      clarifying the similarities and differences between PCC cases with and without
      mucin secretion with regard to biological behavior and clinical course. METHODS:
      Among 644 patients with surgically resected cholangiocarcinoma (1998-2011), 184
      (28 %) patients were considered to have PCC and were enrolled in the study. Those
      patients were divided into two groups based on whether their PCC was mucin
      producing (PCC-M, n = 89) or not (PCC-NM, n = 95). The presence of mucin
      secretion was determined by the cut surface of the specimens and by pathologic
      examination. RESULTS: The clinicopathological features of PCC-M and PCC-NM
      largely overlapped. No significant between-group differences in malignant
      potential characteristics, including the depth of invasion, pathological T
      classification, and regional/periaortic lymph node metastasis, were observed (P =
      0.193, 0.181, 0.083, and 0.674, respectively). However, a few clinicopathological
      differences existed between the two PCC types, i.e., the predominant histological
      type and epithelial subtype (P < 0.001 and P = 0.016, respectively).
      Immunohistochemically, MUC2, MUC5AC, MUC6, and HGM were more frequently expressed
      in PCC-M than PCC-NM (P < 0.002 in all). The disease-specific survival values
      were not significantly different between the two PCC types (PCC-M; 60 % at 5
      year, PCC-NM; 46 %, P = 0.097). CONCLUSION: PCC-M and PCC-NM were similar in
      morphology and prognosis. Although a few clinicopathological differences exist
      between them, their overlapping features and identical survival curves appear to
      justify the lack of a specific treatment modality for either type.

PMID- 25561193
TI  - The relationship between total arterial revascularization and blood transfusion
      following coronary artery bypass grafting.
AB  - BACKGROUND: Blood transfusion adversely affects the outcome of coronary artery
      bypass grafting (CABG), yet blood transfusion after CABG is still common. Total
      arterial revascularisation (TAR) is increasingly used in current practice but its
      impact on postoperative blood transfusion is not known. METHODS: We reviewed the
      cardiothoracic and blood bank databases and collected data for isolated primary
      CABG patients from July 2007 to June 2012, excluding patients who had a single
      graft (n = 148). Perioperative variables of TAR patients (n = 745) were compared
      with patients who had one or more venous grafts (SVG, n = 1,761) for first-time
      isolated CABG. The conduits used in TAR patients were predominantly left internal
      thoracic and radial arteries. Matched group comparison of TAR and SVG patients
      was performed. The association of TAR with blood transfusion was investigated
      using multivariate and matched analysis. RESULTS: Of 2,506 patients, the 745
      (29.7 %) that had TAR were generally younger, with less complex coronary artery
      disease and less often diabetic. After correcting for these by 1:1 matching, the
      mean chest tube drainage and rates of blood transfusion remained significantly
      lower (p < .0001) in TAR patients. Indeed, red cells, platelets and fresh frozen
      plasma were significantly less frequently transfused in TAR patients. By
      multivariate analysis, TAR had an independent effect on reducing blood
      transfusion after CABG [odds ratio (OR) 0.67, 95 % confidence interval (CI) 0.47
      0.97, p = .03]. CONCLUSIONS: TAR achieved predominantly with left internal
      thoracic and radial arteries substantially reduced blood transfusion rates after
      primary CABG. Further studies are warranted.

PMID- 25561192
TI  - Clamshell incision versus left anterolateral thoracotomy. Which one is faster
      when performing a resuscitative thoracotomy? The tortoise and the hare revisited.
AB  - BACKGROUND: The clamshell incision (CI) offers a better exposure than the left
      anterolateral thoracotomy (LAT) as a resuscitative thoracotomy. Most surgeons
      will have to manage a heart wound only once or twice in their career. The
      patient's survival depends on how fast the surgeon can control the heart wound;
      however, it is unclear which of the two incisions allows for faster control in
      the hands of inexperienced surgeons. The aim of this study was to compare the
      time needed to access and control a standardized stab wound to the right
      ventricle, by inexperienced surgical trainees, by LAT or CI; we hypothesized that
      the CI does not take longer than the LAT. METHODS: Sixteen residents were shown a
      video on how to perform both procedures. They were randomly assigned to control a
      standardized stab wound of the right ventricle on perfused human cadavers by LAT
      (n = 8) or CI (n = 8). Access time (skin to maximal exposure), control time
      (maximal exposure until control of the heart wound) and total time (the sum of
      access and control times) were recorded. RESULTS: Total time was 6.62 min [3.20
      8.14] (median [interquartile range]) for LAT and 4.63 min [3.17-6.73] for CI (p =
      0.46). Access time was 2.39 min [1.21-2.76] for LAT and 2.33 min [1.58-4.86] for
      CI (p = 0.34). Control time was 4.16 min [2.32-5.49] for LAT and 1.85 min [1.38
      2.23] for CI (p = 0.018). CONCLUSIONS: The time needed from skin incision until
      cardiac wound control via CI was not longer than via LAT and the easier control
      of the cardiac wound when using CI was confirmed.

PMID- 25561194
TI  - Laparoscopic liver resection in obese patients.
AB  - BACKGROUND: Obesity has been associated with worse postoperative outcomes than
      those for normal weight. Data on the short-term results of laparoscopic liver
      resection (LLR) in patients with obesity are scarce. Furthermore, the long-term
      outcomes of LLR versus open liver resection (OLR) have not been adequately
      assessed. The aims of this study were to analyze the outcomes of obese patients
      undergoing LLR and to compare these to the outcomes of obese patients undergoing
      OLR. METHODS: Data regarding the short-term results from 13 obese patients who
      underwent laparoscopic non-anatomical liver resection were retrospectively
      compared with the data from 69 obese patients who underwent open non-anatomical
      liver resection between 2002 and 2012. The long-term results of patients with
      hepatocellular carcinoma were also compared. RESULTS: A total of 82 patients who
      underwent non-anatomical liver resection in our institution were included. There
      were no differences between the two groups in terms of preoperative patient
      characteristics. The intraoperative blood loss in the laparoscopic group was
      significantly less than that in the open group. There were no significant
      differences in the postoperative complications or postoperative mortality. The
      postoperative hospital stay of the laparoscopic group was significantly shorter
      than that of the open group. CONCLUSIONS: LLR in obese patients results in
      decreased intraoperative blood loss and shorter postoperative hospital stays
      compared with OLR. When performed in selected patients, LLR may be a safe and
      feasible option for obese patients.

PMID- 25561195
TI  - Surgical Care and Health Systems.
AB  - BACKGROUND: While surgical care impacts a wide variety of diseases and conditions
      with non-operative and operative services, both preventive and curative, there
      has been little discussion concerning how surgery might be integrated within the
      health system of a low and middle-income country (LMIC), nor how strengthening
      surgical services may improve health systems and population health. METHODS: We
      reviewed reports from several meetings of the working group on health systems
      strengthening of the Global Initiative for Emergency and Essential Surgical Care,
      and also performed a review of the literature including the search terms
      "surgery," "health system," "developing country," "health systems strengthening,"
      "health information system," "financing," "governance," and "integration."
      RESULTS: The literature search revealed no reports which focused on the
      integration of surgical services within a health system or as a component of
      health system strengthening. A conceptual model of how surgical care might be
      integrated within a health system is proposed, based on the discussions of our
      working group, combined with sources from the medical literature, and utilizing
      the World Health Organization's conceptual model of a health system. CONCLUSIONS:
      Strengthening the delivery of surgical services in LMICs will require inputs at
      multiple levels within a health system, and this effort will require the
      coalescence of committed individuals and organizations, supported by civil
      society.

PMID- 25561196
TI  - Liver function following extended hepatectomy can be accurately predicted using
      remnant liver volume to body weight ratio.
AB  - BACKGROUND: Standardised measurement of remnant liver volume (RLV), where total
      liver volume (TLV) is calculated from patients' body surface area (RLV-sTLV), has
      been advocated. Extrapolating the model of living donor liver transplantation, we
      showed in a pilot study that the simplified RLV/body weight ratio (RLVBWR) was
      accurate in assessing the functional limit of hepatectomy. The aim of the study
      was to compare in a prospective series of extended right hepatectomy the
      predictive value of the RLVBWR and the RLV-sTLV at a cut-off of 0.5% (RLVBWR0.5%)
      and 20% (RLV-sTLV20%), respectively. METHODS: We studied the impact of RLVBWR0.5%
      and of RLV-sTLV20% on three months morbidity and mortality in 74 non-cirrhotic
      patients operated on for malignant tumours. Of these, 47 patients who were not
      included in the initial pilot study were enrolled in a prospective validation
      cohort to reappraise the predictive value of each method. RESULTS: RLVBWR and RLV
      sTLV were highly correlated (Pearson correlation coefficient, 0.966). Three
      months overall and severe morbidity (grade 3b-5) and mortality were significantly
      increased in groups RLVBWR <= 0.5% and RLV-sTLVs <= 20% compared to groups >0.5%
      and >20%, respectively. The sensitivity and specificity in predicting death from
      liver failure were 100 and 84.1% for RLVBWR0.5% and 60 and 94.2% for RLV-sTLV20%,
      respectively. Similar results were observed in the validation cohort for the
      RLVBWR0.5% (lack of statistical power for RLV-sTLV as only 2 patients showed a
      RLV-sTLV <= 20%). CONCLUSIONS: The RLVBWR0.5% is a method of assessing the
      remnant liver that is simple and as reliable as the standardised RLV-sTLV20%.

PMID- 25561198
TI  - Importance of factors affecting serum leptin levels.

PMID- 25561197
TI  - Changing operative strategy from abdominoperineal resection to sphincter
      preservation in T3 low rectal cancer after downstaging by neoadjuvant
      chemoradiation: a preliminary report.
AB  - OBJECTIVE: The objective of this study is to assess oncological outcome after
      changing operative strategy from abdominoperineal resection (APR) to sphincter
      preservation (SP) in T3 low rectal carcinomas downstaged by neoadjuvant
      chemoradiation (nCRT). PATIENTS AND METHODS: This was a prospective observational
      study performed at academic medical centers. Patients with T3 rectal carcinoma,
      (<1 cm from the top of anal sphincter) received long-course neoadjuvant
      chemoradiation. Decision before chemoradiation was APR in all patients. Patients
      who had successful downstaging were included in the study. Low anterior resection
      (LAR) was performed after 8-11 weeks from completion of nCRT. Follow-up duration
      ranged from 4 to 6 years. Salvage surgery was done for local recurrence when
      possible. The primary endpoint of the study was disease-free survival. Secondary
      endpoints were morbidity, mortality, continence, and oncologic results of salvage
      surgery after recurrence. RESULTS: LAR with colorectal or coloanal anastomosis
      were done in 9 and 36 patients, respectively. After a mean follow-up of 57 months
      (range 48-70), local recurrences was reported in 4 patients (8.8 %), one of them
      had also distant metastasis while 2 patients (4.4 %) had only distant metastasis.
      Disease-free and overall survival rates were 87 and 89 %, respectively. Three of
      4 patients with local recurrence (the fourth had liver metastasis) underwent
      salvage APR with free safety margins. Follow-up after salvage surgery for 31, 33,
      and 37 months revealed no recurrences. Wexner continence score <=4 was noted in
      39 patients; while major incontinence (Wexner score >12) was noted in 2 patients.
      CONCLUSIONS: For selected patients of T3 low rectal cancer, changing operative
      strategy from APR to SP after downstaging by nCRT can be done in motivated
      patients with good sphincter function. Disease-free survival rates and continence
      are comparable to patients had APR and to previous publications with decision
      made before nCRT. With strict follow-up, early diagnosis of recurrence and
      salvage surgery with free resection margins can be achieved.

PMID- 25561199
TI  - Epidemiology of actinic keratoses.
AB  - The epidemiology of actinic keratoses (AKs) reflects their causation by
      cumulative sun exposure, with the highest prevalence seen in pale-skinned people
      living at low latitudes and on the most sun-exposed body sites, namely the hands,
      forearms and face. AKs are markers of increased risk of basal cell carcinoma,
      squamous cell carcinoma and melanoma, especially when they are numerous and have
      coalesced into an area of 'field cancerisation'. The major risk factors are male
      sex, advanced age, sun-sensitive complexion, high lifetime sun exposure and
      prolonged immunosuppression. Clinical counts of AKs enable the assessment and
      monitoring of AK burden, but accurate counting is notoriously difficult,
      especially when skin is severely sun damaged. AK counting has been repeatedly
      shown to be unreliable, even among expert dermatologists. Notwithstanding these
      challenges, qualitative assessment of the natural history of AKs shows a high
      turnover, with new lesions developing and with other lesions regressing. A very
      small proportion of AKs undergo malignant transformation, but the precise rate of
      transformation is unknown due to the inaccuracies in monitoring AK lesions over
      time. Primary prevention of AKs is achieved by limiting intense sun exposure
      through sun-protective behaviour, including seeking deep shade, wearing sun
      protective clothing and applying sunscreen regularly to exposed skin, from an
      early age.

PMID- 25561200
TI  - Patients' perspectives on actinic keratosis.
AB  - Many factors influence patients' perspectives on actinic keratosis (AK). The wish
      to keep a sense of control prompts many to seek information, which they then
      interpret according to their personal perspective. Speculations regarding the
      risk of getting skin cancer and emotional reactions may be expected due to
      worries about the worsening of the condition, losing control, and participating
      in UV-related activities. In their contact with physicians, treatment can be an
      additional issue. Treatment of AK may cause pain and may in itself result in a
      perceived diminished quality of life. The Actinic Keratosis Quality of Life
      questionnaire can be used as a valuable tool to represent the effects of
      treatment on quality of life and to classify patient subpopulations. Studies have
      suggested that AK patients are more compliant compared to those with other skin
      diseases. Still fear of stigmatisation may be present during treatment, which may
      disturb social life. Social and personal factors are crucial to patients' coping
      strategies, and financial aspects may have an impact on advisable UV-related
      behaviours. Some AK patients may benefit from interventions to improve their
      stress response capacity. The clear causality of AK requires a change in
      behaviour, which is met by multi-conditioned resistance. The physician should be
      aware that patients might feign acceptance but justify continued UV exposure to
      themselves with a variety of arguments. Tanning is of great importance for the
      self-esteem of many AK patients, and tanning addiction should be considered.

PMID- 25561201
TI  - Photodamage: all signs lead to actinic keratosis and early squamous cell
      carcinoma.
AB  - Ultraviolet (UV) radiation is likely to drive the initiation and progression of
      skin cancer from actinic keratosis to squamous cell carcinoma. Signs of
      photodamage occur at multiple steps. UV radiation damages many cellular
      constituents, including lipids, proteins and DNA, all of which are likely to
      contribute to UV-induced skin cancer. Two biological events culminating from
      photodamage are mutations in the genes critical to the control of cell division,
      differentiation and invasion and immunosuppression. DNA photodamage, if
      unrepaired prior to cell division, can result in the incorporation of an
      incorrect nucleotide into newly synthesised DNA. Mutations in critical genes
      contribute to carcinogenesis. Photodamage to proteins such as those involved in
      DNA repair or proteins or lipids involved in cellular signalling can interfere
      with this repair process and contribute to mutagenesis. Mutations in key genes,
      including TP53, BRM, PTCH1, and HRAS, contribute to skin carcinogenesis. UV also
      damages immunity. Photodamage to DNA and signalling lipids as well as other
      molecular changes are detrimental to the key cells that regulate immunity.
      Photodamaged dendritic cells and altered responses by mast cells lead to the
      activation of T and B regulatory cells that suppress immunity to the protein
      products of UV-mutated genes. This stops the immune response from its protective
      function of destroying mutated cells, enabling the transformed cells to progress
      to skin cancer. UV appears to play a pivotal role at each of these steps, and
      therefore, signs of photodamage point to the development of skin cancer.

PMID- 25561202
TI  - Dysregulation of epidermal growth factor receptor in actinic keratosis and
      squamous cell carcinoma.
AB  - The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase. Its
      correct function is required for normal skin development and homeostasis, while
      dysregulation of EGFR signalling results in cellular hyper-proliferation and
      defects in differentiation, leading to impaired wound healing, the development of
      psoriasis-like lesions, structural and functional defects of hair follicles and
      tumourigenesis. Actinic keratosis, which is also known as solar keratosis,
      develops in sun-exposed areas of the skin. These are often called 'premalignant
      lesions' and are said to represent early squamous cell carcinoma (SCC) in situ,
      although debate over their classification continues. Anti-EGFR therapies have
      been approved for the treatment of several malignancies and are undergoing trials
      for others [1], including advanced cutaneous squamous cell carcinoma (CSCC).
      However, a number of questions remain regarding the treatment of CSCC with anti
      EGFR inhibitors. A lower number of CSCC tumours are EGFR positive in comparison
      to other types of tumours, such as head and neck SCC (HNSCC), and it has been
      suggested that patients should be selected on the basis of high tumour EGFR
      expression. However, there are reports of patients with tumours showing no EGFR
      positive staining responding to anti-EGFR therapy. EGFR is an oncogenic driver in
      many tumours. Does it drive the transformation of actinic keratosis to a
      tumourigenic phenotype? Many such questions remain, and here, we discuss the role
      of EGFR in SCC and its functions during the different stages of skin cancer
      development.

PMID- 25561203
TI  - The actinic keratosis virome: can we prevent squamous cell carcinoma with a
      vaccine?
AB  - Squamous skin cancer, which is commonly called squamous cell carcinoma (SCC),
      represents an immunological puzzle. The major skin cancers (SCC, basal cell
      carcinoma, Merkel cell carcinoma, and melanoma) and actinic keratosis (AK), as a
      potential precursor lesion of SCC, are common in immune-suppressed patients. The
      increased risk of a particular cancer in chronically immune-suppressed patients
      is a feature of those cancers for which a virus contributes to the aetiology.
      However, amongst the skin cancers mentioned, a causal virus (Merkel polyomavirus)
      has been identified only for Merkel tumours. It is therefore reasonable to
      determine whether a virus or viruses contribute to the risk of the development of
      AK and SCC. This chapter will first consider the limitations of the methodologies
      available for determining the roles of viruses in the aetiologies of AK and SCC
      and review current evidence of the contribution of a virus to the risk of
      developing these diseases. It will then consider why there might be an increased
      risk of AK in chronically immune-suppressed patients although no relevant virus
      can be identified.

PMID- 25561204
TI  - Do actinic keratoses and superficial squamous cell carcinomas have a specific
      immunoprofile?
AB  - The link between actinic keratosis (AK), squamous cell carcinoma (SCC), and a
      fully functional immune system has been frequently observed but is poorly
      understood. Elderly and immunosuppressed individuals and those with weakened
      immune systems caused by disease are all at increased risk of developing AK
      and/or SCC. This risk is particularly enhanced at sites that receive high levels
      of ultraviolet exposure from the sun, which is thought to be a driver of DNA
      mutations in the skin. The immune system appears to play a key role in preventing
      these mutations from progressing to malignant disease. AK is often considered to
      be a pre-cancerous lesion that may develop into SCC. However, the vast majority
      of AKs, in contrast to SCCs, regress naturally or in response to immune-modifying
      medications. The cellular mechanisms involved in this immune-based process remain
      elusive and raise the following question: does the immune make-up or immune
      functionality within AK differ fundamentally from that within SCC? This chapter
      will outline the skin as a site of considerable immunological activity, highlight
      the consequences of dysregulated immune activity in the skin, and discuss what
      little we know of immune infiltrates and their associated functions within AK and
      SCC.

PMID- 25561205
TI  - Mouse models for actinic keratosis and squamous cell carcinoma.
AB  - This manuscript focuses on the use of mice to study the genetics and biology of
      cutaneous squamous cell carcinoma (SCC). Mice develop actinic keratosis-like
      lesions and SCC resembling those seen in humans. As an animal model, the mouse
      provides great experimental flexibility and has been useful in investigating
      aspects of the genetics and biology of SCC that are difficult to study in humans.
      We discuss the pros and cons of the various murine models available. How well
      mouse pathology in general mimics human disease remains an open question due to
      the vast differences in animal strain backgrounds and the fact that only one
      strain is typically tested in any particular experiment. Nonetheless, the murine
      epidermis is thinner than the human epidermis, and this must be kept in mind when
      making inferences from mechanistic data obtained with mice. We outline new
      strategies for non-biased screens to discover genes driving SCC progression. Such
      work has revealed a very complex interactive molecular network, and as with other
      complex diseases, the picture is being pieced together using systems biology
      strategies to which mouse tumour models are amenable. Such approaches do not
      focus on single genes or proteins but try to integrate the complex interactions
      of many types of genetic and biological information.

PMID- 25561206
TI  - Keratinocyte cancer and its precursors in organ transplant patients.
AB  - Organ transplant recipients (OTRs) have a 65- to 250-fold increased risk of the
      development of cutaneous squamous cell carcinoma in the wake of
      immunosuppression. The combination of ultraviolet light and properties of
      immunosuppressive drugs potentiate skin cancer formation. Due to decreased
      peritumoral inflammation, the thickness and invasion of epithelial skin lesions
      are often underestimated clinically. Rapid tumor progression and aggressive tumor
      behaviors occur frequently in the OTR population. Tenderness and pain in a skin
      lesion may indicate its potential invasion beyond the basal membrane and the need
      for surgical removal. All patients should receive extensive education on
      ultraviolet avoidance and protection. In particular, a preventive and aggressive
      treatment of actinic keratosis in areas of field cancerization is recommended to
      cut down on the high morbidity and avoid the mortality associated with actinic
      keratosis and invasive squamous cell carcinoma in OTRs.

PMID- 25561207
TI  - Clinical features of actinic keratoses and early squamous cell carcinoma.
AB  - Clinically, there is a continuum between actinic keratosis, intraepidermal
      carcinoma (also known as squamous cell carcinoma in situ) and early squamous cell
      carcinoma that makes a reliable distinction between these entities extremely
      difficult. Each of the lesions in this continuum can be quite variable in
      clinical appearance, and there are often no clear distinguishing features, making
      it difficult to determine whether an individual actinic keratosis has evolved
      into intraepidermal carcinoma or invasive squamous cell carcinoma.

PMID- 25561208
TI  - The many clinico-pathologic faces of actinic keratosis: an atlas.
AB  - Actinic keratoses (AKs) are intraepithelial neoplasms formed by atypical
      keratinocyte proliferation. Histopathologically, typical AKs are characterized by
      a slightly thickened epidermis, usually with irregular downward buds,
      orthokeratosis alternating with parakeratosis ('pink and blue') with loss of the
      underlying granular layer and a disarrangement of the epidermis with atypical
      keratinocytes at the basal layer. There are several histopathological variants of
      AK according to the different degrees of keratinocytic atypia, epidermal
      hyperplasia/atrophy, inflammation and pigmentation. Some authors consider AK an
      early in situ squamous cell carcinoma and propose a classification of AK based on
      the extent of atypical keratinocytes in the epidermis.

PMID- 25561209
TI  - Dermoscopy of actinic keratosis, intraepidermal carcinoma and squamous cell
      carcinoma.
AB  - In the realm of keratinocyte skin cancer, specific dermoscopic patterns that are
      associated with different stages of progression have been identified, which
      allows for an improved clinical diagnosis and differentiation actinic keratosis,
      intraepidermal carcinoma (also commonly named Bowen's disease, squamous cell
      carcinoma in situ or intraepidermal carcinoma) and invasive squamous cell
      carcinoma. Moreover, in times of increasing availability of topical treatment
      options for actinic keratoses, the knowledge of specific patterns associated with
      different grades and subtypes aids in the treatment choice and monitoring of the
      treatment response.

PMID- 25561210
TI  - The future of keratinocyte skin cancer surveillance: automated image analysis to
      identify and monitor keratinocyte dysplasia.
AB  - Clinical assessment of actinic keratosis is known to be a variable process;
      however, there are currently no non-invasive alternatives for objectively
      assessing the condition besides excision and histopathology. While a number of
      technologies for examining potential actinic keratoses are under development,
      each of these still requires subjective human assessment. The existing approaches
      focus on assessing colour and texture features in clinical-scale images, such as
      those from dermoscopy and digital photography, and on structural or cellular
      characteristics in cellular-scale images, such as those from multiphoton
      microscopy and reflectance confocal microscopy. The future of actinic keratosis
      management is likely to be a combination of analysing regional photography to
      determine potential lesion locations and analysis of the structural and cellular
      features by reflectance confocal microscopy for an in vivo pathology diagnosis.

PMID- 25561211
TI  - Reflectance confocal microscopy: hallmarks of keratinocyte cancer and its
      precursors.
AB  - Actinic keratosis is a common result of severe sun damage and is usually present
      on sun-exposed skin. Reflectance confocal microscopy is a non-invasive clinical
      imaging modality that results in quasi-histological, en face skin images. In this
      chapter, we review the available literature and distill the common features of
      actinic keratosis, as seen by reflectance confocal microscopy. Finally, several
      examples are discussed in the context of matching clinical, histopathological and
      reflectance confocal microscopy images. Of all of the morphological features of
      actinic keratoses, the epidermal honeycomb pattern is the most telling when
      viewing the lesions using reflectance confocal microscopy. In the near future, we
      expect the definition of consensus criteria for diagnosing actinic keratoses and
      differentiating this precursor lesion.

PMID- 25561212
TI  - Optical coherence tomography and its role for delineating the thickness of
      keratinocyte dysplasia and neoplasia.
AB  - Optical coherence tomography (OCT) can produce cross-sectional and en face, non
      invasive, real-time images of skin. OCT produces high-resolution images at a
      micrometre resolution and has a maximum 2-mm penetration depth, which places OCT
      in the imaging gap between ultrasound and confocal microscopy. Much OCT research
      has been performed on keratinocyte dysplasia and neoplasia, primarily including
      basal cell carcinoma (BCC) and actinic keratosis. In regards to BCC and actinic
      keratosis, architectural disarray of the epidermis is an overall characteristic
      finding in OCT images. OCT can reliably differentiate between normal and lesional
      skin, which is of great importance when identifying tumour borders. Therefore, it
      has been suggested that OCT may aid in the evaluation of sub-surface tumour
      margins prior to surgical and non-invasive treatments of keratinocyte neoplastic
      lesions. Studies on in vivo presurgical margin assessments found that OCT
      correctly identified the laterally defined tumour margin in 84% of cases and that
      the borders determined by the surgeon never came below the OCT margin, indicating
      the utility of OCT. These reports imply a scope for reducing the final size of an
      excision defect using OCT. The main limitation to assessing tumour thickness
      using OCT is its maximum scan depth of 2 mm, indicating that the primary
      potential of OCT may lie in the evaluation of superficial tumours.

PMID- 25561213
TI  - Teledermatology: its use in the detection and management of actinic keratosis.
AB  - Teledermatology can profoundly improve access to medical services for those who
      may have limited access to dermatology due to workforce shortages or limitations
      in their mobility or who are located far from providers. Two common methods of
      teledermatology are synchronous live methods, where the patient and doctor
      directly communicate, and asynchronous store-and-forward methods, where the
      patient and doctor independently provide and assess the medical information.
      Teledermatology has been tested for its safety, feasibility and accuracy for a
      number of dermatological conditions, including the early detection of skin
      cancer, and is considered safe, feasible and accurate. Studies have reported
      somewhat better results for synchronous than asynchronous methods, possibly due
      to the loss of information if no direct patient doctor contact was feasible.
      However, asynchronous methods are easier to organise, require less-sophisticated
      technology and are more widely accessible and convenient for both patients and
      doctors. No study to date has focused solely on teledermatology for actinic
      keratosis, but such lesions are typically found during teledermatology
      examinations for other main target lesions. In studies where such results were
      reported, actinic keratoses seemed to be readily identifiable for
      teledermatologists, and adequate management and treatment can be suggested within
      remote consultations.

PMID- 25561214
TI  - Conventional treatment of actinic keratosis: an overview.
AB  - Nonsurgical procedures are the first-line treatment for actinic keratosis (AK).
      The choice of therapy is based on AK features and patient characteristics.
      Numerous randomized clinical trials and open-label studies have provided robust
      data on the efficacy and tolerability of conventional topical therapies, such as
      cryotherapy, photodynamic therapy, or treatment with 5-fluorouracil, diclofenac,
      or imiquimod. Cryotherapy is recommended to treat single AK lesions (lesion
      directed therapy), while topical medical therapies are used to treat multiple
      lesions on an entire sun-damaged area (field therapy) and have the advantage of
      highlighting and treating both visible and invisible lesions. Combined or
      sequential therapies have been proposed to improve treatment efficacy, while
      medication breaks between treatment cycles or lowering drug concentrations is
      used to increase treatment tolerability/adherence. The use of a field therapy to
      treat multiple lesions on a large area (the entire face or a balding scalp),
      followed by a lesion-targeted therapy for a specific recurrent or resistant AK
      lesion, is becoming an increasingly popular approach. Regarding surgical
      procedures, curettage with or without electrodessication and dermabrasion are
      seldom used, while excision is indicated when AK progression to invasive squamous
      cell carcinoma is clinically suspected. Despite the availability of most such
      treatments for more than a decade and their common use in clinical practice,
      there is still a need for long-term follow-up studies to better determine the
      recurrence rate and for comparative studies to develop a truly patient-tailored
      therapy.

PMID- 25561215
TI  - Field cancerization: from molecular basis to selective field-directed management
      of actinic keratosis.
AB  - The incidence of non-melanoma skin cancer (NMSC), including actinic keratosis
      (AK), squamous cell carcinoma (SCC), Bowen's Disease (BD) and basal cell
      carcinoma (BCC), is increasing. UVA and UVB radiation lead to genetic alterations
      in keratinocytes, which eventually result in skin cancer. In the concept of field
      cancerization of the skin, genetically altered keratinocytes accumulate over an
      area exposed to UV radiation. Field treatment not only clears clinically visible
      NMSC lesions but also potentially targets subclinical 'sleeping' cell patches and
      fields. Topical treatments are available for the field-directed management of
      NMSC. They are either self-administered by the patient (ingenol mebutate,
      diclofenac, imiquimod or 5-FU) or administered by the dermatologist (photodynamic
      therapy (PDT)). This article discusses the treatment options with respect to
      their efficacy, tolerability and selectivity. Selective treatment options for
      atypic keratinocytes include imiquimod, ingenol mebutate, diclofenac and PDT. PDT
      yields 100% treatment compliance because it is always administered by the
      treating dermatologist. The efficacy rates achieved with PDT significantly exceed
      those of the patient-administered topicals. The first clinical trials assessing
      the effects of PDT on field cancerization clinically, histologically and
      immunochemically have been conducted and have yielded promising results.
      Preventive effects and a delay in the re-occurrence of NMSC have been observed in
      animal experiments of ingenol mebutate and PDT, whereas for the latter, clinical
      data are already available.

PMID- 25561216
TI  - Update on photodynamic treatment for actinic keratosis.
AB  - Photodynamic therapy (PDT) is an attractive treatment option for actinic
      keratoses (AKs), as large skin areas can be treated with high response rates and
      superior cosmetic outcome. The efficacy of 5-aminolevulinic acid (ALA)-PDT and
      methyl aminolevulinate (MAL)-PDT for AK has been proven in multiple studies, and
      this treatment is recommended in numerous consensus works and therapy guidelines.
      Moreover, a self-adhesive ALA patch has been approved for the PDT of AK. In a
      phase III study, ALA-patch-PDT was superior to cryotherapy and placebo in the
      treatment of mild to moderate AK on the face and scalp, and pre-treatment of the
      lesions and additional light occlusion was unnecessary when using the patch. ALA
      with a proprietary nanoemulsion is another newly marketed ALA gel that has been
      approved for the treatment of mild to moderate AK on the head. ALA was combined
      with a nanoemulsion to achieve increased chemical stability of the active
      ingredient and to enhance skin penetration. One study found that ALA was superior
      to MAL in the treatment of AK on the face or scalp. Daylight-PDT is a simpler and
      more tolerable treatment procedure for PDT, and three randomised studies have
      shown that daylight-PDT is an effective and pain-free treatment for AK; however,
      the procedure is limited by the need for a sufficient light dose and outdoor
      temperature. Ablative fractional laser resurfacing prior to MAL has been used to
      improve the PDT response of thick AK. However, more intense acute skin reactions
      and long-term adverse events in ablative fractional laser resurfacing-PDT
      compared with PDT-treated skin were found, which might limit the use of the
      intensified treatment.

PMID- 25561217
TI  - Laser treatment and its implications for photodamaged skin and actinic keratosis.
AB  - Treatment of widespread actinic keratoses (AKs) and extensive photodamage is a
      challenge. One of the treatment options is laser therapy, whereby physicians have
      the option of using ablative lasers (CO2 and Erbium Yttrium Aluminium Garnet) or
      nonablative fractional laser systems. With ablative laser systems, the
      superficial layers of the skin are ablated, including epidermal and superficial
      dermal actinic damage. Re-epithelialization occurs from uninvolved skin and
      keratinocytes from follicles. When using a CO2 laser, additional cosmetic
      improvements are a result of removal and tightening of the photodamaged collagen
      in the superficial dermis. The most important risks of this treatment are
      scarring and dyspigmentation. These risks are lessened when using fractional
      lasers, which produce small columns of ablation or coagulation in the skin,
      leaving the surrounding skin intact. This treatment may be combined with topical
      agents. Existing evidence suggests that both ablative laser resurfacing and
      fractional laser treatments are effective in reducing AKs and photodamage.
      Although these treatment modalities are widely used and clinical experiences are
      positive, large comparative studies are remarkably scarce. Still, laser
      resurfacing has a place in the (field) treatment of widespread AKs and extensive
      photodamage.

PMID- 25561218
TI  - Ingenol mebutate: from common weed to cancer cure.
AB  - Actinic keratosis, which is a potential precursor of squamous cell carcinoma, is
      a common skin condition in fair-skinned adults worldwide. Actinic keratosis may
      be treated with 'lesion-directed' approaches and/or 'field-directed' therapies,
      the latter of which include imiquimod, diclofenac and 5-fluorouracil. The topical
      formulation of ingenol mebutate, which is a protein kinase C inhibitor derived
      from the sap of the plant Euphorbia peplus, is the newest addition to the
      existing arsenal of field-directed treatments. Its mechanism of action primarily
      involves the induction of primary necrosis and initiation of an inflammatory
      response characterized by the migration of neutrophils to the treated area. The
      gel is available in two strengths: 150 micrograms/g to be applied to lesions on
      the face and scalp once daily for 3 consecutive days and 500 micrograms/g for
      application to lesions on the trunk and extremities for 2 consecutive days.
      Clinical studies have supported claims of the convenience of its application and
      efficacy; however, the literature provides scant information on comparative
      efficacy rates and side-effect profiles.

PMID- 25561219
TI  - Oral nicotinamide and actinic keratosis: a supplement success story.
AB  - Nicotinamide has shown potential as a safe and effective intervention for the
      prevention of malignant and premalignant skin lesions. Recent studies have shown
      that nicotinamide, in both oral and topical forms, is able to prevent ultraviolet
      induced immunosuppression in humans [1,2,3] and mice [4,5]. Immunosuppression is
      a known factor for the progression of premalignant lesions, such as actinic
      keratosis [6]. Murine studies have shown that nicotinamide is also able to
      protect against photocarcinogenesis [4,5]. Preliminary human studies suggest that
      nicotinamide may help prevent skin cancers and enhance the regression of actinic
      keratoses.

PMID- 25561221
TI  - Scheduling in the context of resident duty hour reform.
AB  - Fuelled by concerns about resident health and patient safety, there is a general
      trend in many jurisdictions toward limiting the maximum duration of consecutive
      work to between 14 and 16 hours. The goal of this article is to assist
      institutions and residency programs to make a smooth transition from the previous
      24- to 36-hour call system to this new model. We will first give an overview of
      the main types of coverage systems and their relative merits when considering
      various aspects of patient care and resident pedagogy. We will then suggest a
      practical step-by-step approach to designing, implementing, and monitoring a
      scheduling system centred on clinical and educational needs in the context of
      resident duty hour reform. The importance of understanding the impetus for change
      and of assessing the need for overall workflow restructuring will be explored
      throughout this process. Finally, as a practical example, we will describe a
      large, university-based teaching hospital network's transition from a traditional
      call-based system to a novel schedule that incorporates the new 16-hour duty
      limit. 

PMID- 25561222
TI  - Morin, a flavonoid from moraceae, induces apoptosis by induction of BAD protein
      in human leukemic cells.
AB  - Evidence suggests that phytochemicals can safely modulate cancer cell biology and
      induce apoptosis. Here, we investigated the anti-cancer activity of morin, a
      flavone originally isolated from members of the Moraceae family in human leukemic
      cells, focusing on apoptosis. An anti-cancer effect of morin was screened with
      several human leukemic cell lines. U937 cells were most sensitive to morin, where
      it induced caspase-dependent apoptosis in a dose-dependent manner. It also
      induced loss of MMP (DeltaPsim) along with cytochrome c release, down-regulated
      Bcl-2 protein, and up-regulated BAX proteins. The apoptotic activity of morin was
      significantly attenuated by Bcl-2 augmentation. In conclusion, morin induced
      caspase-dependent apoptosis through an intrinsic pathway by upregulating BAD
      proteins. In addition, Bcl-2 protein expression is also important in morin
      induced apoptosis of U937 cells. This study provides evidence that morin might
      have anticancer properties in human leukemic cells. 

PMID- 25561223
TI  - Synergistic effect of bolus exposure to zinc oxide nanoparticles on bleomycin
      induced secretion of pro-fibrotic cytokines without lasting fibrotic changes in
      murine lungs.
AB  - Zinc oxide (ZnO) nanoparticles are widely used in various products, and the
      safety evaluation of this manufactured material is important. The present study
      investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO
      nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was
      induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl
      mice were divided into BLM-treated and non-treated groups. In each treatment
      group, 0, 10, 20 or 30 ug of ZnO nanoparticles were delivered into the lungs
      through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs
      were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single
      bolus of ZnO nanoparticles resulted in severe, but transient inflammatory
      infiltration and thickening of the alveolar septa in the lungs, along with the
      increase of total and differential cell counts in BLAF. The BALF level of
      interleukin (IL)-1beta and transforming growth factor (TGF)-beta was increased at
      Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO
      exposure was detected on IL-1beta and monocyte chemotactic protein (MCP)-1 in
      BALF. The present study demonstrated the synergistic effect of pulmonary exposure
      to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro
      fibrotic cytokines in the lungs. 

PMID- 25561224
TI  - Reduced 5-methylcytosine level as a potential progression predictor in patients
      with T1 or non-invasive urothelial carcinoma.
AB  - This study aims to elucidate the level of DNA methylation in urothelial
      carcinomas (UCs) using 5-methylcytosine (5-MeC) immunohistochemistry (IHC). We
      examined the relationship among 5-MeC levels, DNA (cytosine-5)-methyltransferase
      1 (DNMT1) immunostaining levels, and clinicopathologic features. Tissue samples
      included 23 normal urothelia and 150 urothelial neoplasia, which comprised 40 non
      invasive and 110 invasive UCs. The levels of 5-MeC and DNMT1 were assessed based
      on their immunoreactivities and then divided into low and high levels. In
      addition, we collected information on clinical variables, pathologic features,
      and recurrent status from patient questionnaires and medical records. Chi-square
      test and multivariate logistic regression model were used for analyses. Results
      showed that 5-MeC levels were positively associated with DNMT1 levels in UC (p =
      0.0288). Both 5-MeC and DNMT1 were low in approximately 50% (76/150) of UC. The
      percentage of low 5-MeC levels was higher in invasive UC (65/110; 59%) than in
      normal urothelia (2/23; 13%) and non-invasive UC (18/40; 45%). Clinical factors
      were independently associated with low 5-MeC levels after adjusting for age and
      sex, including cancer stages II-IV, presence of UC in situ, and marked
      inflammation. Low 5-MeC levels in stage I invasive UC were not significantly
      different from those of non-invasive tumors (p = 0.8478). Low DNMT1 levels were
      only associated with UC with squamous differentiation (p = 0.0365). Neither 5-MeC
      nor DNMT1 levels were associated with UC recurrence. In conclusion, a low 5-MeC
      level could predict the progression of UC invasion into muscle. 

PMID- 25561225
TI  - Zinc-alpha-2-glycoprotein: a candidate biomarker for colon cancer diagnosis in
      Chinese population.
AB  - Zinc-alpha-2-glycoprotein (AZGP1) is a 41-kDa secreted glycoprotein, which has
      been detected in several malignancies. The diagnostic value of AZGP1 in serum of
      prostate and breast cancer patients has been reported. Analyzing "The Cancer
      Genome Atlas" data, we found that in colon cancer AZGP1 gene expression was
      upregulated at transcriptional level. We hypothesized that AZGP1 could be used as
      a diagnostic marker of colon cancer. First, we confirmed AZGP1 expression was
      higher in a set of 28 tumor tissues than in normal colonic mucosa tissues by real
      time quantitative PCR and western blot in a Chinese population. We verified that
      serum concentration of AZGP1 was higher in 120 colon cancer patients compared
      with 40 healthy controls by ELISA (p < 0.001). Then receiver-operating
      characteristic (ROC) curve analysis was used to evaluate the predictive
      diagnostic value of AZGP1 in serum. The area under the curve (AUC) of AZGP1 was
      0.742 (p < 0.001, 95% confidence interval (CI) = 0.656-0.827) in between the AUC
      of carcinoembryonic antigen (CEA) and the AUC of CA19-9, suggesting that
      predictive diagnostic value of AZGP1 is between CEA and Carbohydrate 19-9 (CA19
      9). The combination of AZGP1 with traditional serum biomarkers, CEA and CA19-9,
      could result in better diagnostic results. To further validate the diagnostic
      value of AZGP1, a tissue microarray containing 190 samples of primary colon
      cancer tissue paired with normal colonic tissue was analysed and the result
      showed that AZGP1 was significantly upregulated in 68.4% (130 of 190) of the
      primary cancer lesions. In contrast, there was a weakly positive staining in
      29.5% (56 of 190) of the normal colonic tissue samples (p < 0.001). Leave-one-out
      cross-validation was performed on the serum data, and showed that the diagnostic
      value of AZGP1 had 63.3% sensitivity and 65.0% specificity. Combination of AZGP1,
      CEA and CA19-9 had improved diagnosis value accuracy with 74.2% sensitivity and
      72.5% specificity. These results suggest that AZGP1 is a useful diagnostic
      biomarker in tissues and serum from a Chinese population. 

PMID- 25561227
TI  - Chlamydia pneumoniae and oxidative stress in cardiovascular disease: state of the
      art and prevention strategies.
AB  - Chlamydia pneumoniae, a pathogenic bacteria responsible for respiratory tract
      infections, is known as the most implicated infectious agent in atherosclerotic
      cardiovascular diseases (CVDs). Accumulating evidence suggests that C. pneumoniae
      induced oxidative stress may play a critical role in the pathogenesis of CVDs.
      Indeed, the overproduction of reactive oxygen species (ROS) within macrophages,
      endothelial cells, platelets and vascular smooth muscle cells (VSMCs) after C.
      pneumoniae exposure, has been shown to cause low density lipoprotein oxidation,
      foam cell formation, endothelial dysfunction, platelet adhesion and aggregation,
      and VSMC proliferation and migration, all responsible for the typical
      pathological changes of atherosclerotic plaque. The aim of this review is to
      improve our insight into C. pneumoniae-induced oxidative stress in order to
      suggest potential strategies for CVD prevention. Several antioxidants, acting on
      multi-enzymatic targets related to ROS production induced by C. pneumoniae, have
      been discussed. A future strategy for the prevention of C. pneumoniae-associated
      CVDs will be to target chlamydial HSP60, involved in oxidative stress. 

PMID- 25561228
TI  - Bioactive chemical constituents from the brown alga Homoeostrichus formosana.
AB  - A new chromene derivative, 2-(4',8'-dimethylnona-3'E,7'-dienyl)-8-hydroxy-2,6
      dimethyl-2H-chromene (1) together with four known natural products,
      methylfarnesylquinone (2), isololiolide (3), pheophytin a (4), and beta-carotene
      (5) were isolated from the brown alga Homoeostrichus formosana. The structure of
      1 was determined by extensive 1D and 2D spectroscopic analyses. Acetylation of 1
      yielded the monoacetylated derivative 2-(4',8'-dimethylnona-3'E,7'-dienyl)-8
      acetyl-2,6-dimethyl-2H-chromene (6). Compounds 1-6 exhibited various levels of
      cytotoxic, antibacterial, and anti-inflammatory activities. Compound 2 was found
      to display potent in vitro anti-inflammatory activity by inhibiting the
      generation of superoxide anion (IC50 0.22 +/- 0.03 MUg/mL) and elastase release
      (IC50 0.48 +/- 0.11 MUg/mL) in FMLP/CB-induced human neutrophils. 

PMID- 25561226
TI  - Association between ADIPOQ +45T>G polymorphism and type 2 diabetes: a systematic
      review and meta-analysis.
AB  - Recently, a number of studies have reported the association between the single
      nucleotide polymorphisms (SNPs) +45 T>G polymorphism in the adiponectin (ADIPOQ)
      gene and type 2 diabetes mellitus (T2DM) risk, though the results are
      inconsistent. In order to obtain a more precise estimation of the relationship, a
      meta-analysis was performed. In this current study, the Medline, Embase, Pubmed,
      ISI Web of Knowledge, Ovid, Science Citation Index Expanded Database, Wanfang
      Database, and China National Knowledge Infrastructure were searched for eligible
      studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to
      estimate the strength of association. Forty-five publications were included in
      the final meta-analysis with 9986 T2DM patients and 16,222 controls for ADIPOQ
      +45 T>G polymorphism according to our inclusion and exclusion criteria. The +45
      T>G polymorphism was associated with an overall significantly increased risk of
      T2DM (G vs. T: OR = 1.18, 95% CI = 1.06-1.32; The dominant model: OR = 1.18, 95%
      CI = 1.03-1.33; The recessive model: OR = 1.47, 95% CI = 1.20-1.78; The
      homozygous model: OR = 1.62, 95% CI = 1.25-2.09; Except the heterozygous model:
      OR = 1.11, 95% CI = 0.98-1.24). Subgroup analysis revealed a significant
      association between the +45 T>G polymorphism and T2D in an Asian population.
      Thus, this meta-analysis indicates that the G allele of the ADIPOQ +45 T>G
      polymorphisms associated with a significantly increased risk of T2DM in the Asian
      population.

PMID- 25561229
TI  - Gene mutation analysis in EGFR wild type NSCLC responsive to erlotinib: are there
      features to guide patient selection?
AB  - Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung
      cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor
      (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to
      TKI, with unknown molecular mechanisms of sensitivity. We considered a case
      series of 34 EGFR wt NSCLC patients responsive to erlotinib after at least one
      line of therapy. Responsive patients were matched with an equal number of non
      responsive EGFR wt patients. A panel of 26 genes, for a total of 214 somatic
      mutations, was analyzed by MassARRAY(r) System (Sequenom, San Diego, CA, USA). A
      15% KRAS mutation was observed in both groups, with a prevalence of G12C in non
      responders (80% vs. 40% in responders). NOTCH1, p53 and EGFR-resistance-related
      mutations were found more frequently in non-responders, whereas EGFR-sensitizing
      mutations and alterations in genes involved in proliferation pathways were more
      frequent in responders. In conclusion, our findings indicate that p53, NOTCH1 and
      exon 20 EGFR mutations seem to be related to TKI resistance. KRAS mutations do
      not appear to influence the TKI response, although G12C mutation is more frequent
      in non-responders. Finally, the use of highly sensitive methodologies could lead
      to the identification of under-represented EGFR mutations potentially associated
      with TKI sensitivity. 

PMID- 25561231
TI  - Improvement of the fluorescence intensity during a flow cytometric analysis for
      rice protoplasts by localization of a green fluorescent protein into
      chloroplasts.
AB  - Protoplasts have been a useful unicellular system for various molecular
      biological analyses based on transient expression and single cell analysis using
      fluorescence-activated cell sorting (FACS), widely used as a powerful method in
      functional genomics. Despite the versatility of these methods, some limits based
      on low fluorescence intensity of a flow cytometric analysis (FCA) using
      protoplasts have been reported. In this study, the chloroplast targeting of
      fluorescent proteins (FPs) led to an eight-fold increase in fluorescence
      intensity and a 4.5-fold increase of transfection ratio from 14.7% to 65.7% as
      compared with their targeting into the cytoplasm. Moreover, the plot data of FCA
      shows that 83.3% of the K-sGFP population is under the threshold level, regarded
      as a non-transgenic population with background signals, while 65.7% of the K-sGFP
      population is spread on overall intervals. To investigate the reason underlying
      this finding, mRNA/protein levels and transfection efficiency were analyzed, and
      results suggest that mRNA/protein levels and transfection ratio are not much
      different between K-sGFP and KR-sGFP. From those results, we hypothesized that
      the difference of fluorescence intensity is not only derived from cellular events
      such as molecular level or transfection efficiency. Taken together, we suggest
      that the translocation of FPs into chloroplasts contributes to the improvement of
      fluorescence intensity in FCA and, apparently, plays an important role in
      minimizing the loss of the transfected population. Our study could be usefully
      applicable for highly sensitive FACS and FCA-investigations of green tissue. 

PMID- 25561230
TI  - Motor, visual and emotional deficits in mice after closed-head mild traumatic
      brain injury are alleviated by the novel CB2 inverse agonist SMM-189.
AB  - We have developed a focal blast model of closed-head mild traumatic brain injury
      (TBI) in mice. As true for individuals that have experienced mild TBI, mice
      subjected to 50-60 psi blast show motor, visual and emotional deficits, diffuse
      axonal injury and microglial activation, but no overt neuron loss. Because
      microglial activation can worsen brain damage after a concussive event and
      because microglia can be modulated by their cannabinoid type 2 receptors (CB2),
      we evaluated the effectiveness of the novel CB2 receptor inverse agonist SMM-189
      in altering microglial activation and mitigating deficits after mild TBI. In
      vitro analysis indicated that SMM-189 converted human microglia from the pro
      inflammatory M1 phenotype to the pro-healing M2 phenotype. Studies in mice showed
      that daily administration of SMM-189 for two weeks beginning shortly after blast
      greatly reduced the motor, visual, and emotional deficits otherwise evident after
      50-60 psi blasts, and prevented brain injury that may contribute to these
      deficits. Our results suggest that treatment with the CB2 inverse agonist SMM-189
      after a mild TBI event can reduce its adverse consequences by beneficially
      modulating microglial activation. These findings recommend further evaluation of
      CB2 inverse agonists as a novel therapeutic approach for treating mild TBI. 

PMID- 25561232
TI  - Nutritional composition and antioxidant capacity in edible flowers:
      characterisation of phenolic compounds by HPLC-DAD-ESI/MSn.
AB  - Edible flowers are commonly used in human nutrition and their consumption has
      increased in recent years. The aim of this study was to ascertain the nutritional
      composition and the content and profile of phenolic compounds of three edible
      flowers, monks cress (Tropaeolum majus), marigold (Tagetes erecta) and paracress
      (Spilanthes oleracea), and to determine the relationship between the presence of
      phenolic compounds and the antioxidant capacity. Proximate composition, total
      dietary fibre (TDF) and minerals were analysed according to official methods:
      total phenolic compounds (TPC) were determined with Folin-Ciocalteu's reagent,
      whereas antioxidant capacity was evaluated using Trolox Equivalent Antioxidant
      Capacity (TEAC) and Oxygen Radical Absorbance Capacity (ORAC) assays. In
      addition, phenolic compounds were characterised by HPLC-DAD-MSn. In relation to
      the nutritional value, the edible flowers had a composition similar to that of
      other plant foods, with a high water and TDF content, low protein content and
      very low proportion of total fat-showing significant differences among samples.
      The levels of TPC compounds and the antioxidant capacity were significantly
      higher in T. erecta, followed by S. oleracea and T. majus. Thirty-nine different
      phenolic compounds were tentatively identified, with flavonols being the major
      compounds detected in all samples, followed by anthocyanins and hydroxycynnamic
      acid derivatives. In T. erecta small proportions of gallotannin and ellagic acid
      were also identified. 

PMID- 25561234
TI  - Identification of retinopathy of prematurity related miRNAs in hyperoxia-induced
      neonatal rats by deep sequencing.
AB  - Retinopathy of prematurity (ROP) remains a major problem for many preterm
      infants. MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate
      gene expression at the posttranscriptional level and have been studied in many
      diseases. To understand the roles of miRNAs in ROP model rats, we constructed two
      small RNA libraries from the plasma of hyperoxia-induced rats and normal
      controls. Sequencing data revealed that 44 down-regulated microRNAs and 22 up
      regulated microRNAs from the hyperoxia-induced rats were identified by deep
      sequencing technology. Some of the differentially expressed miRNAs were confirmed
      by quantitative reverse transcription-PCR (qRT-PCR). A total of 594 target genes
      of the differentially expressed microRNAs were identified using a bioinformatics
      approach. Functional annotation analysis indicated that a number of pathways
      might be involved in angiogenesis, cell proliferation and cell differentiation,
      which might be involved in the genesis and development of ROP. The elevated
      expression level of the vascular endothelial growth factor (VEGF) protein in the
      hyperoxia-induced neonatal rats was also confirmed by enzyme linked immunosorbent
      assay (ELISA). This study provides some insights into the molecular mechanisms
      that underlie ROP development, thereby aiding the diagnosis and treatment of this
      disease. 

PMID- 25561233
TI  - Pathogenesis of target organ damage in hypertension: role of mitochondrial
      oxidative stress.
AB  - Hypertension causes target organ damage (TOD) that involves vasculature, heart,
      brain and kidneys. Complex biochemical, hormonal and hemodynamic mechanisms are
      involved in the pathogenesis of TOD. Common to all these processes is an
      increased bioavailability of reactive oxygen species (ROS). Both in vitro and in
      vivo studies explored the role of mitochondrial oxidative stress as a mechanism
      involved in the pathogenesis of TOD in hypertension, especially focusing on
      atherosclerosis, heart disease, renal failure, cerebrovascular disease. Both
      dysfunction of mitochondrial proteins, such as uncoupling protein-2 (UCP2),
      superoxide dismutase (SOD) 2, peroxisome proliferator-activated receptor gamma
      coactivator 1-alpha (PGC-1alpha), calcium channels, and the interaction between
      mitochondria and other sources of ROS, such as NADPH oxidase, play an important
      role in the development of endothelial dysfunction, cardiac hypertrophy, renal
      and cerebral damage in hypertension. Commonly used anti-hypertensive drugs have
      shown protective effects against mitochondrial-dependent oxidative stress.
      Notably, few mitochondrial proteins can be considered therapeutic targets on
      their own. In fact, antioxidant therapies specifically targeted at mitochondria
      represent promising strategies to reduce mitochondrial dysfunction and related
      hypertensive TOD. In the present article, we discuss the role of mitochondrial
      oxidative stress as a contributing factor to hypertensive TOD development. We
      also provide an overview of mitochondria-based treatment strategies that may
      reveal useful to prevent TOD and reduce its progression. 

PMID- 25561235
TI  - Exploring the Arabidopsis proteome: influence of protein solubilization buffers
      on proteome coverage.
AB  - The study of proteomes provides new insights into stimulus-specific responses of
      protein synthesis and turnover, and the role of post-translational modifications
      at the systems level. Due to the diverse chemical nature of proteins and
      shortcomings in the analytical techniques used in their study, only a partial
      display of the proteome is achieved in any study, and this holds particularly
      true for plant proteomes. Here we show that different solubilization and
      separation methods have profound effects on the resulting proteome. In
      particular, we observed that the type of detergents employed in the
      solubilization buffer preferentially enriches proteins in different functional
      categories. These include proteins with a role in signaling, transport, response
      to temperature stimuli and metabolism. This data may offer a functional bias on
      comparative analysis studies. In order to obtain a broader coverage, we propose a
      two-step solubilization protocol with first a detergent-free buffer and then a
      second step utilizing a combination of two detergents to solubilize proteins. 

PMID- 25561236
TI  - Responses to oxidative and heavy metal stresses in cyanobacteria: recent
      advances.
AB  - Cyanobacteria, the only known prokaryotes that perform oxygen-evolving
      photosynthesis, are receiving strong attention in basic and applied research. In
      using solar energy, water, CO2 and mineral salts to produce a large amount of
      biomass for the food chain, cyanobacteria constitute the first biological barrier
      against the entry of toxics into the food chain. In addition, cyanobacteria have
      the potential for the solar-driven carbon-neutral production of biofuels.
      However, cyanobacteria are often challenged by toxic reactive oxygen species
      generated under intense illumination, i.e., when their production of
      photosynthetic electrons exceeds what they need for the assimilation of inorganic
      nutrients. Furthermore, in requiring high amounts of various metals for growth,
      cyanobacteria are also frequently affected by drastic changes in metal
      availabilities. They are often challenged by heavy metals, which are increasingly
      spread out in the environment through human activities, and constitute persistent
      pollutants because they cannot be degraded. Consequently, it is important to
      analyze the protection against oxidative and metal stresses in cyanobacteria
      because these ancient organisms have developed most of these processes, a large
      number of which have been conserved during evolution. This review summarizes what
      is known regarding these mechanisms, emphasizing on their crosstalk. 

PMID- 25561238
TI  - Development and application of a label-free fluorescence method for determining
      the composition of gold nanoparticle-protein conjugates.
AB  - A method was developed for determining the composition of the conjugates between
      gold nanoparticles and proteins based on the intrinsic fluorescence of unbound
      protein molecules. The fluorescence was evaluated after separation of the
      conjugates from the reaction mixture by centrifugation. Gold nanoparticles
      obtained using the citrate technique (average diameter 24 nm) were conjugated at
      pH 5.4 with the following four proteins: human immunoglobulin G (IgG), bovine
      serum albumin (BSA), recombinant streptococcal protein G (protein G), and Kunitz
      type soybean trypsin inhibitor (STI). The compositions of these conjugates were
      determined using the developed method. The conjugate compositions were dependent
      on the concentration of the added protein, and in all cases reached saturation.
      The equilibrium dissociation constants of the gold nanoparticle conjugates with
      IgG, BSA, protein G, STI in the initial section of the concentration dependence
      curve were 4, 6, 10, and 15 nM, respectively. Close to saturation, the
      corresponding values were 25, 76, 175, and 100 nM, respectively. The maximal
      binding capacities of a single gold nanoparticle for IgG, BSA, Protein G, and STI
      were 52, 90, 500, and 550, respectively, which agrees well with the hypothesis of
      monolayer immobilization. 

PMID- 25561240
TI  - [Pancreatic adenocarcinoma - early symptoms and screening].
AB  - Pancreatic adenocarcinoma is a dismal disease with a very serious prognosis and a
      very low 5-year survival. Local symptoms are present at a late stage of the
      disease and in the majority of cases do not enable radical surgery. Intervention
      is possible only in locally restricted tumor and remains the only chance of
      significant survival. At present, two early symptoms of this growth are known.
      They include impaired glucose tolerance or diabetes similar to but not identical
      with diabetes type 2, and a decrease of the body mass. They precede by a period
      of 2-3 years local symptoms that are late and cause the bad prognosis. The
      earlier diagnosis of pancreatic adenocarcinoma represents an urgent and serious
      task. The project of a screening program based on the use of the early symptoms
      may move the diagnosis of pancreatic adenocarcinoma to the earlier stage of the
      disease. The key-players for the most important first step of this program are
      general practitioners and ambulatory diabetologists.

PMID- 25561237
TI  - Cytokine-modulating strategies and newer cytokine targets for arthritis therapy.
AB  - Cytokines are the key mediators of inflammation in the course of autoimmune
      arthritis and other immune-mediated diseases. Uncontrolled production of the pro
      inflammatory cytokines such as interferon-gamma (IFN-gamma), tumor necrosis
      factor alpha (TNFalpha), interleukin-6 (IL-6), and IL-17 can promote autoimmune
      pathology, whereas anti-inflammatory cytokines including IL-4, IL-10, and IL-27
      can help control inflammation and tissue damage. The pro-inflammatory cytokines
      are the prime targets of the strategies to control rheumatoid arthritis (RA). For
      example, the neutralization of TNFalpha, either by engineered anti-cytokine
      antibodies or by soluble cytokine receptors as decoys, has proven successful in
      the treatment of RA. The activity of pro-inflammatory cytokines can also be
      downregulated either by using specific siRNA to inhibit the expression of a
      particular cytokine or by using small molecule inhibitors of cytokine signaling.
      Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists
      delivered via gene therapy has proven to be an effective approach to regulate
      autoimmunity. Unexpectedly, under certain conditions, TNFalpha, IFN-gamma, and
      few other cytokines can display anti-inflammatory activities. Increasing
      awareness of this phenomenon might help develop appropriate regimens to harness
      or avoid this effect. Furthermore, the relatively newer cytokines such as IL-32,
      IL-34 and IL-35 are being investigated for their potential role in the
      pathogenesis and treatment of arthritis. 

PMID- 25561241
TI  - [Overweight, obesity and underweight prevalence in 7-year-old children in the
      Czech Republic since 1951].
AB  - BACKGROUND: Childhood overweight prevalence increases worldwide. The aim of the
      study was to clarify the change in underweight, overweight and obesity in seven
      year old Czech children since 1951. METHODS: Data on underweight, overweight and
      obesity prevalence were obtained using repeated cross-sectional surveys. In 1951
      2001 six Czech National Anthropological Surveys were conducted. In years 2008 and
      2010 the data were collected as a part of the WHO Europe initiated Childhood
      Obesity Surveillance Initiative (COSI). The data were evaluated according to WHO
      references (2007), in 2010 results were assessed also according to the Czech
      reference standards (1991). RESULTS: From 1951, overweight and obesity prevalence
      increased in both genders up to 2001. In 2008, a modest decrease in obesity and
      stable overweight prevalence in girls and in boys a slight increase in obesity
      and decrease in overweight were found. In 2010, a modest increase in obesity
      prevalence in girls achieving the levels assessed in 2001 and stable level of
      overweight were found; in boys the levels remained as in 2008. BMI z score
      increased significantly between 1951 and 2001. CONCLUSION: These results suggest
      stabilisation of obesity and overweight prevalence in the Czech Republic in 7
      years old children during the last 10 years. Underweight prevalence has remained
      low.

PMID- 25561242
TI  - [Is obesity an adverse prognostic factor for pulmonary manifestations of
      influenza? Lesson from complicated disease course H1N1].
AB  - Influenza viruses cause annual epidemics that occur at different times in both
      the northern and southern hemisphere. In cases of seasonal influenza these are
      usually mild forms of the disease, which rarely lead to death of the patient.
      Vulnerable groups include the elderly, the young or those with comorbidities,
      where the virus affects tens of thousands of victims around the world.
      Occasionally, however, large epidemics appear caused by a dangerous variant of a
      new virus, which is usually characterized by high contagiousness and
      pathogenicity (virulence). Consequently, it is often accompanied by a complicated
      disease course and associated with high mortality. In 2009, a viral pandemic
      disease marked pH1N1 2009 Influenza A appeared. Even though the initial
      predictions were far worse, the course of influenza caused by this virus was
      often complicated by acute respiratory failure in the form of acute respiratory
      distress syndrome (ARDS). This formed part of the wider multiple organ failure
      syndrome (MODS). This type of virus often infects younger age groups and is more
      contagious compared to the seasonal flu. In order to illustrate the complicated
      forms of viral infections pH1N1 2009 Influenza A we present three case studies
      which demonstrate complicated pulmonary manifestation, which take the primary
      form of ARDS.

PMID- 25561243
TI  - Parallel electrochemical treatment system and application for identifying acid
      stable oxygen evolution electrocatalysts.
AB  - Many energy technologies require electrochemical stability or preactivation of
      functional materials. Due to the long experiment duration required for either
      electrochemical preactivation or evaluation of operational stability, parallel
      screening is required to enable high throughput experimentation. Imposing
      operational electrochemical conditions to a library of materials in parallel
      creates several opportunities for experimental artifacts. We discuss the
      electrochemical engineering principles and operational parameters that mitigate
      artifacts in the parallel electrochemical treatment system. We also demonstrate
      the effects of resistive losses within the planar working electrode through a
      combination of finite element modeling and illustrative experiments. Operation of
      the parallel-plate, membrane-separated electrochemical treatment system is
      demonstrated by exposing a composition library of mixed-metal oxides to oxygen
      evolution conditions in 1 M sulfuric acid for 2 h. This application is
      particularly important because the electrolysis and photoelectrolysis of water
      are promising future energy technologies inhibited by the lack of highly active,
      acid-stable catalysts containing only earth abundant elements. 

PMID- 25561239
TI  - Lipid metabolism, apoptosis and cancer therapy.
AB  - Lipid metabolism is regulated by multiple signaling pathways, and generates a
      variety of bioactive lipid molecules. These bioactive lipid molecules known as
      signaling molecules, such as fatty acid, eicosanoids, diacylglycerol,
      phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1
      phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the
      activation or regulation of different signaling pathways. Lipid metabolism
      participates in the regulation of many cellular processes such as cell growth,
      proliferation, differentiation, survival, apoptosis, inflammation, motility,
      membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid
      molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial
      membrane permeability and activating different enzymes including caspases. In
      this review, we discuss recent data in the fields of lipid metabolism, lipid
      mediated apoptosis, and cancer therapy. In conclusion, understanding the
      underlying molecular mechanism of lipid metabolism and the function of different
      lipid molecules could provide the basis for cancer cell death rationale, discover
      novel and potential targets, and develop new anticancer drugs for cancer therapy.

PMID- 25561244
TI  - Non-invasive estimation of skin thickness from hyperspectral imaging and
      validation using echography.
AB  - BACKGROUND: The skin is the largest organ and is subject to the greatest exposure
      to outside elements throughout one's lifetime. Current data by the American
      Academy of Dermatology suggests that approximately ten people die each hour
      worldwide due to skin related conditions. Cancers such as melanoma are growths
      that originate in the epidermis. Therefore, an accurate and non-invasive method
      to estimate skin constitutive elements can play an important clinical role in
      detecting the early onset of skin tumors. It can also serve as a valuable tool
      for research and development in cosmetics and pharmaceuticals in general.
      METHODS: In our prior work, we developed a method that combined a physics-based
      model of human skin with machine learning and Hyperspectral imaging to non
      invasively estimate physiological skin parameters, including melanosomes,
      collagen, oxygen saturation, and blood volume. In this work, we extend that model
      to also estimate skin thickness. Moreover, for the first time, we develop a
      protocol to test our methodology for skin thickness estimation using Ultrasound
      to acquire a gold standard dataset. RESULTS: We tested our methodology for skin
      thickness estimation on a dataset of 48 Hyperspectral signatures obtained in vivo
      from six patients under IRB at Johns Hopkins Hospital. We found mean absolute
      errors on the order of the Ultrasound resolution (i.e., our gold standard).
      DISCUSSION: This is the first study of its kind to validate skin thickness
      estimates using a gold standard. Our preliminary results constitute a proof-of
      concept that hyperspectral-based methods can accurately and non-invasively
      estimate skin thickness in clinical settings.

PMID- 25561245
TI  - Nephroprotective effects of ferulic acid, Z-ligustilide and E-ligustilide
      isolated from Angelica sinensis against cisplatin toxicity in vitro.
AB  - Cisplatin (CisPt), a chemotherapeutic drug applied against solid tumors, is
      highly detrimental to the kidney. The risk of acute kidney injury implies
      adequate patient hydration to ensure sufficient diuresis; this strategy, now
      implemented in clinical practice, remains however incompletely satisfactory. New
      pharmacological approaches relying on the discovery of bioactive compounds need
      to be developed. Based on previous studies reporting renoprotective activities
      for extracts of Angelica sinensis (Oliv.) Diels roots, three of its major active
      compounds, ferulic acid, Z-ligustilide and E-ligustilide, were investigated for
      possible alleviation of CisPt-induced nephrotoxicity. Five phenomena involved in
      acute kidney injury and subsequent fibrosis were investigated: (i) modulation of
      cell survival via reduction of the apoptosis rate; (ii) reduction of oxidative
      stress; (iii) improvement of tubular regeneration capacities through
      proliferation and migration; (iv) limitation of extracellular matrix and collagen
      deposition; and (v) prevention of the dedifferentiation processes via the beta
      catenin pathway. Ferulic acid emerged as the most potent compound for alleviating
      cell death and collagen deposition, and for enhancing cell regeneration
      capacities. It also partially inhibited the beta-catenin pathway, but was
      ineffective in lowering oxidative stress. Z- and E-ligustilides, however, were
      effective for limiting the oxidative stress, but only moderately affected other
      parameters. Ferulic acid appears to be a promising nephroprotective drug lead
      deserving further preclinical investigation. 

PMID- 25561246
TI  - Inhibition of in vitro metabolism of testosterone in human, dog and horse liver
      microsomes to investigate species differences.
AB  - Testosterone hydroxylation was investigated in human, canine and equine liver
      microsomes and in human and canine single CYPs. The contribution of the CYP
      families 1, 2 and 3 was studied using chemical inhibitors. Testosterone
      metabolites were analyzed by HPLC. The metabolites androstenedione, 6beta- and
      11beta-hydroxytestosterone were found in microsomes of all species, but the
      pattern of metabolites varied within species. Androstenedione was more prominent
      in the animal species, and an increase over time was seen in equines.
      Testosterone hydroxylation was predominantly catalyzed by the CYP3A subfamily in
      all three species. While CYP2C9 did not metabolise testosterone, the canine
      ortholog CYP2C21 produced androstenedione. Quercetin significantly inhibited
      6beta- and 11beta-hydroxytestosterone in all species investigated, suggesting
      that CYP2C8 is involved in testosterone metabolism, whereas sulfaphenazole
      significantly inhibited the formation of 6beta- and 11beta-hydroxytestosterone in
      human microsomes, at 60 min in equine microsomes, but not in canine microsomes. A
      contribution of CYP2B6 in testosterone metabolism was only found in human and
      equine microsomes. Inhibition of 17beta-hydroxysteroid dehydrogenase 2 indicated
      its involvement in androstenedione formation in humans, increased androstenedione
      formation was found in equines and no involvement in canines. These findings
      provide improved understanding of differences in testosterone biotransformation
      in animal species.

PMID- 25561247
TI  - Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a
      progressive or relapsing and remitting paralysing illness probably due to an
      autoimmune response which should benefit from corticosteroids. Non-randomised
      studies suggest that corticosteroids are beneficial. Two commonly used
      corticosteroids are prednisone and prednisolone. Both are usually given as oral
      tablets. Prednisone is converted into prednisolone in the liver so that the
      effect of the two drugs is usually the same. Another corticosteroid, called
      dexamethasone, is more potent and is used in smaller doses. OBJECTIVES: To assess
      the effects of corticosteroid treatment compared to placebo or no treatment for
      CIDP and to compare the effects of different corticosteroid regimes. SEARCH
      METHODS: On 27 October 2014 we searched the Cochrane Neuromuscular Disease Group
      Specialized Register, CENTRAL, MEDLINE, and EMBASE for randomised trials of
      corticosteroids for CIDP. We searched three other databases for information to
      include in the Discussion, and clinical trials registries for ongoing trials.
      SELECTION CRITERIA: We included randomised or quasi-randomised trials of
      treatment with any form of corticosteroids or adrenocorticotrophic hormone for
      CIDP, diagnosed by an internationally accepted definition. DATA COLLECTION AND
      ANALYSIS: Two authors extracted the data and assessed risk of bias independently.
      The primary outcome was intended to be change in disability, with change in
      impairment after 12 weeks as a secondary outcome, and adverse events. MAIN
      RESULTS: In one non-blinded randomised controlled trial (RCT) with 35 eligible
      participants, the primary outcome for this review was not available. The trial
      had a high risk of bias. Twelve of 19 participants treated with prednisone,
      compared with five of 16 participants randomised to no treatment, had improved
      neuropathy impairment scores after 12 weeks; the risk ratio (RR) for improvement
      was 2.02 (95% confidence interval (CI) 0.90 to 4.52). Adverse events were not
      reported in detail, but one prednisone-treated participant died.In a double-blind
      RCT comparing daily standard-dose oral prednisolone with monthly high-dose oral
      dexamethasone in 40 participants, none of the outcomes for this review were
      available. The trial had a low risk of bias. There were no significant
      differences in remission (RR 1.11; 95% CI 0.50 to 2.45 in favour of monthly
      dexamethasone) or change in disability or impairment after one year. Eight of 16
      in the prednisolone, and seven of 24 in the dexamethasone group deteriorated.
      Adverse events were similar with each regimen, except that sleeplessness and moon
      facies (moon-shaped appearance of the face) were significantly less common with
      monthly dexamethasone.Experience from large non-randomised studies suggests that
      corticosteroids are beneficial, but long-term use causes serious side effects.
      AUTHORS' CONCLUSIONS: Very low quality evidence from one small, randomised trial
      did not show a statistically significant benefit from oral prednisone compared
      with no treatment. Nevertheless, corticosteroids are commonly used in practice.
      According to moderate quality evidence from one RCT, the efficacy of high-dose
      monthly oral dexamethasone was not statistically different from that of daily
      standard-dose oral prednisolone. Most adverse events occurred with similar
      frequencies in both groups, but sleeplessness and moon facies were significantly
      less common with monthly dexamethasone. Further research is needed to identify
      factors which predict response.

PMID- 25561248
TI  - Repositioning for treating pressure ulcers.
AB  - BACKGROUND: Pressure, from lying or sitting on a particular part of the body
      results in reduced oxygen and nutrient supply, impaired drainage of waste
      products and damage to cells. If a patient with an existing pressure ulcer
      continues to lie or bear weight on the affected area, the tissues become depleted
      of blood flow and there is no oxygen or nutrient supply to the wound, and no
      removal of waste products from the wound, all of which are necessary for healing.
      Patients who cannot reposition themselves require assistance. International best
      practice advocates the use of repositioning as an integral component of a
      pressure ulcer management strategy. This review has been conducted to clarify the
      role of repositioning in the management of patients with pressure ulcers.
      OBJECTIVES: To assess the effects of repositioning patients on the healing rates
      of pressure ulcers. SEARCH METHODS: For this third update we searched the
      Cochrane Wounds Group Specialised Register (searched 28 August 2014); The
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2014, Issue 7); Ovid MEDLINE (2013 to August Week 3 2014); Ovid MEDLINE (In
      Process & Other Non-Indexed Citations 29 August, 2014); Ovid EMBASE (2012 to 29
      August, 2014); and EBSCO CINAHL (2012 to 27 August 2014). SELECTION CRITERIA: We
      considered randomised controlled trials (RCTs) comparing repositioning with no
      repositioning, or RCTs comparing different repositioning techniques, or RCTs
      comparing different repositioning frequencies for the review. Controlled clinical
      trials (CCTs) were only to be considered in the absence of RCTs. DATA COLLECTION
      AND ANALYSIS: Two authors independently assessed titles and, where available,
      abstracts of the studies identified by the search strategy for their eligibility.
      We obtained full versions of potentially relevant studies and two authors
      independently screened these against the inclusion criteria. MAIN RESULTS: We
      identified no studies that met the inclusion criteria. AUTHORS' CONCLUSIONS:
      Despite the widespread use of repositioning as a component of the management plan
      for individuals with existing pressure ulcers, no randomised trials exist that
      assess the effects of repositioning patients on the healing rates of pressure
      ulcers. Therefore, we cannot conclude whether repositioning patients improves the
      healing rates of pressure ulcers. The effect of repositioning on pressure ulcer
      healing needs to be evaluated.

PMID- 25561249
TI  - Excipient variability and its impact on dosage form functionality.
AB  - Pharmaceutical excipients are essential components of most modern dosage forms.
      Although defined as pharmacologically inert, excipients can be thought of as the
      true enablers of drug product performance. Unintentional variability in the
      properties of the excipients may be unavoidable, albeit minimizable. The
      variability may originate from the source, the excipient-manufacturing process,
      or during the manufacturing of dosage forms. Excipient variability may have a
      range of influences on their functionality and performance in the dosage form. A
      better understanding of these influences on the critical quality attributes of
      the final product is of prime importance. Modern analytical tools provide a
      significant assistance in characterizing excipient variability to achieve this
      understanding. The principles and concepts of Quality-by-Design, process
      analytical technology, and design space, provide a holistic risk-based approach
      toward manufacture and application of excipients in pharmaceutical formulations.
      The International Pharmaceutical Excipients Council (IPEC) has developed
      guidelines for proper selection, use, and evaluation of excipients in
      pharmaceutical products.

PMID- 25561250
TI  - Transcriptional characteristics associated with lichenysin biosynthesis in
      Bacillus licheniformis from Chinese Maotai-flavor liquor making.
AB  - This work investigated the biosynthetic mechanism of lichenysin, the newly
      identified nonvolatile matrix component in Chinese liquors. Transcriptomes were
      analyzed in three producers, Bacillus licheniformis CGMCC 3961, 3962, and 3963,
      which were isolated from Maotai-flavor liquor-making process and produced 386.3,
      553.5, and 795.2 MUg/L lichenysin in a simulative liquor fermentation process.
      Lichenysin synthetase genes lchAA-AD in these three producers were expressed much
      more highly than those of the nonproducer B. licheniformis ATCC 14580 (>18.4
      fold). In addition, ABC transporters were the most significant responsive
      metabolic pathway, and the expression levels of peptide transporter genes
      dppABCDE all increased more than 19.2-fold. When B. licheniformis CGMCC 3963 was
      cultured in synthetic medium, the expression of dppABCDE and lichenysin both
      increased with the addition of casein hydrolysate (containing various peptides).
      This indicated that peptide would act as a substrate for lichenysin synthesis.
      This work sheds new light on the mechanism for lichenysin biosynthesis. 

PMID- 25561251
TI  - An ecotoxicological evaluation of soil fertilized with biogas residues or mining
      waste.
AB  - This paper presents an ecotoxicological evaluation of soil fertilized with biogas
      digestate (BD) or mining waste (MS). The study was performed under pot experiment
      conditions. BD was added at a dose of 1.5 and 3% to the soil. MS was applied at a
      dose of 10 and 20%. Samples were collected at the beginning of the experiment and
      after 180 and 360 days from the start of the study. In addition, a parallel
      experiment with the addition of CaO was done. This was designed to eliminate the
      adverse effect of low soil pH on the test organisms. A battery of
      ecotoxicological tests was used based on tests with plants (Phytotoxkit F),
      microorganisms (Microtox), and crustaceans (Daphtoxkit F). In most cases, the
      obtained results showed that the investigated wastes had a stimulating effect on
      the growth of Lepidium sativum roots. The highest content of BD was an exception
      since it inhibited the growth of L. sativum roots. After adding BD and MS, both
      the luminescence of Vibrio fischeri and the mortality of Daphnia magna was at a
      similar level to that in the control soil. An exception was the significant
      increase in the mortality of D. magna after 48 h for soil with 3% BD. The tests
      performed after 6 and 12 months showed that, with time, the toxicity of the waste
      amended soil fluctuated, but ultimately decreased in most cases compared to the
      control. The effect of the addition of CaO on the examined toxicity parameters
      was different and depended on the experimental variant.

PMID- 25561252
TI  - Metal-based particles in human amniotic fluids of fetuses with normal karyotype
      and congenital malformation--a pilot study.
AB  - This study explores the inorganic composition of amniotic fluid in healthy human
      fetuses and fetuses with congenital malformation with a special attention to
      presence of metal-based solid particles. Amniotic fluid originates from maternal
      blood and provides fetus mechanical protection and nutrients. In spite of this
      crucial role, the environmental impact on the composition of amniotic fluid
      remains poorly studied. The samples of human amniotic fluids were obtained by
      amniocentesis, including both healthy pregnancies and those with congenital
      malformations. The samples were analysed using several techniques, including
      Raman microspectroscopy, scanning electron microscopy with energy-dispersed
      spectrometry (SEM-EDS), Fourier transform infrared spectroscopy (FTIR) and X-ray
      diffraction (XRD) analysis. Several metal-based particles containing barium,
      titanium, iron, and other elements were detected by SEM-EDS and Raman
      microspectroscopy. XRD analysis detected only sodium chloride as the main
      component of all amniotic fluid samples. Infrared spectroscopy detected protein
      like organic components. Majority of particles were in form of agglomerates up to
      tens of micrometres in size, consisting of mainly submicron particles. By
      statistical analysis (multiple correspondence analysis), it was observed that
      groups of healthy and diagnosed fetuses form two separate groups and therefore,
      qualitative differences in chemical composition may have distinct biological
      impact. Overall, our results suggest that metal-based nanosized pollutants
      penetrate into the amniotic fluid and may affect human fetuses. 

PMID- 25561253
TI  - Approach to spatialize local to long-range atmospheric metal input (Cd, Cu, Hg,
      Pb) in epiphytic lichens over a meso-scale area (Pyrenees-Atlantiques,
      southwestern France).
AB  - Geographically based investigations into atmospheric bio-monitoring usually
      provide information on concentration or occurrence data and spatial trends of
      specific contaminants over a specified study area. In this work, an original
      approach based on geographic information system (GIS) was used to establish metal
      contents (Hg, Cu, Pb, and Cd) in epiphytic lichens from 90 locations as
      atmospheric bio-monitors over a meso-scale area (Pyrenees-Atlantiques,
      southwestern France). This approach allows the integration of the heterogeneity
      of the territory and optimization of the sampling sites based on both
      socioeconomical and geophysical parameters (hereafter defined as urban,
      industrial, agricultural, and forested areas). The sampling strategy was first
      evaluated in several sites (n = 15) over different seasons and years in order to
      follow the temporal variability of the atmospheric metal input in lichens. The
      results demonstrate that concentration ranges remain constant over different
      sampling periods in "rural" areas (agricultural and forested). Higher variability
      is observed in the "anthropized" urban and industrial areas in relation to local
      atmospheric inputs. In this context, metal concentrations in lichens over the
      whole study show that (1) Hg and Cd are homogeneous over the whole territory
      (0.14 +/- 0.04 and 0.38 +/- 0.26 mg/kg, respectively), whereas (2) Cu and Pb are
      more concentrated in "anthropized" areas (9.3 and 11.9 mg/kg, respectively) than
      in "rural" ones (6.8 and 6.0 mg/kg, respectively) (Kruskall-Wallis, K(Cu) = 13.7
      and K(Pb) = 9.7, p < 0.00001). They also showed a significant local enrichment
      for all metals in many locations in the Pays Basque (West) mainly due to metal
      and steel industrial activities. This confirms the local contribution of this
      contamination source over a wider geographic scale. A multiple linear regression
      model was applied to give an integrated spatialization of the data. This showed
      significant relationships for Pb and Cu (adjusted r (2) of 0.39 and 0.45,
      respectively), especially with regards to variables such as industry and road
      densities (source factors) and elevation or water balance (remote factors). These
      results show that an integrated GIS-based sampling strategy can improve
      biomonitoring data distribution and allows better differentiation of local and
      long-range contamination. 

PMID- 25561254
TI  - Substance flow analysis of mercury in Turkey for policy decision support.
AB  - Identification and quantification of mercury flows in Turkey are essential for
      better policy development regarding to the implementation of water-related
      legislation. To this end, substance flow analysis (SFA) of mercury in Turkey was
      conducted in order to identify and quantify mercury releases to different
      environmental compartments and help policy decision makers to better understand
      their options to reduce mercury flows. For the quantification of mercury flows,
      United Nations Environment Programme (UNEP) Mercury Toolkit, which is develop by
      UNEP Chemicals Branch with the aim of assisting countries to develop their own
      mercury inventory, was used. Results of the study showed that a total of 34.61 t
      of mercury is released annually from the activities in Turkey to different
      environmental compartments. It was found that most of the mercury releases were
      to the atmosphere (74 %) and smaller amounts were to land (21 %) and to water (5
      %). Mercury naturally found in the lithosphere was found to be responsible for
      most of the releases while intentional mercury uses have smaller shares and
      decreasing importance because of the phasing out of mercury.

PMID- 25561255
TI  - Endophytic bacteria take the challenge to improve Cu phytoextraction by
      sunflower.
AB  - Endophytic bacteria from roots and crude seed extracts of a Cu-tolerant
      population of Agrostis capillaris were inoculated to a sunflower metal-tolerant
      mutant line, and their influence on Cu tolerance and phytoextraction was assessed
      using a Cu-contaminated soil series. Ten endophytic bacterial strains isolated
      from surface-sterilized A. capillaris roots were mixed to prepare the root
      endophyte inoculant (RE). In parallel, surface-sterilized seeds of A. capillaris
      were crushed in MgSO4 to prepare a crude seed extract containing seed endophytes
      (SE). An aliquot of this seed extract was filtered at 0.2 MUm to obtain a
      bacterial cell-free seed extract (SEF). After surface sterilization, germinated
      sunflower seeds were separately treated with one of five modalities: no treatment
      (C), immersion in MgSO4 (CMg) or SEF solutions and inoculation with RE or SE. All
      plants were cultivated on a Cu-contaminated soil series (13-1020 mg Cu kg(-1)).
      Cultivable RE strains were mostly members of the Pseudomonas genera, and one
      strain was closely related to Labrys sp. The cultivable SE strains belonged
      mainly to the Bacillus genera and some members of the Rhodococcus genera. The
      treatment effects depended on the soil Cu concentration. Both SE and SEF plants
      had a higher Cu tolerance in the 13-517 mg Cu kg(-1) soil range as reflected by
      increased shoot and root DW yields compared to control plants. This was
      accompanied by a slight decrease in shoot Cu concentration and increase in root
      Cu concentration. Shoot and root DW yields were more promoted by SE than SEF in
      the 13-114 mg Cu kg(-1) soil range, which could reflect the influence of seed
      located bacterial endophytes. At intermediate soil Cu (416-818 mg Cu kg(-1)
      soil), the RE and CMg plants had lower shoot Cu concentrations than the control,
      SE and SEF plants. At high total soil Cu (617-1020 mg Cu kg(-1)), root DW yield
      of RE plants slightly increased and their root Cu concentration rose by up to 1.9
      fold. In terms of phytoextraction efficiency, shoot Cu removal was increased for
      sunflower plants inoculated with crude and bacterial cell-free seed extracts by
      1.3- to 2.2-fold in the 13-416 mg Cu kg(-1) soil range. Such increase was mainly
      driven by an enhanced shoot DW yield. The number and distribution of endophytic
      bacteria in the harvested sunflower tissues must be further examined. 

PMID- 25561256
TI  - Substrates specialization in lipid compounds and hydrocarbons of Marinobacter
      genus.
AB  - The impact of petroleum contamination and of burrowing macrofauna on abundances
      of Marinobacter and denitrifiers was tested in marine sediment mesocoms after 3
      months incubation. Quantification of this genus by qPCR with a new primer set
      showed that the main factor favoring Marinobacter abundance was hydrocarbon
      amendment followed by macrofauna presence. In parallel, proportion of nosZ
      harboring bacteria increased in the presence of marcrofauna. Quantitative finding
      were explained by physiological data from a set of 34 strains and by genomic
      analysis of 16 genomes spanning 15 different Marinobacter-validated species
      (Marinobacter hydrocarbonoclasticus, Marinobacter daeopensis, Marinobacter
      santoriniensis, Marinobacter pelagius, Marinobacter flavimaris, Marinobacter
      adhaerens, Marinobacter xestospongiae, Marinobacter algicola, Marinobacter
      vinifirmus, Marinobacter maritimus, Marinobacter psychrophilus, Marinobacter
      lipoliticus, Marinobacter manganoxydans, Marinobacter excellens, Marinobacter
      nanhaiticus) and 4 potential novel ones. Among the 105 organic electron donors
      tested in physiological analysis, Marinobacter pattern appeared narrow for almost
      all kinds of organic compounds except lipid ones. Strains of this set could
      oxidize a very large spectrum of lipids belonging to glycerolipids, branched,
      fatty acyls, and aromatic hydrocarbon classes. Physiological data were comforted
      by genomic analysis, and genes of alkane 1-monooxygenase, haloalkane
      dehalogenase, and flavin-binding monooxygenase were detected in most genomes.
      Denitrification was assessed for several strains belonging to M.
      hydrocarbonoclasticus, M. vinifirmus, Marinobacter maritinus, and M. pelagius
      species indicating the possibility to use nitrate as alternative electron
      acceptor. Higher occurrence of Marinobacter in the presence of petroleum appeared
      to be the result of a broader physiological trait allowing this genus to use
      lipids including hydrocarbon as principal electron donors.

PMID- 25561257
TI  - Leydig cell number and sperm production decrease induced by chronic ametryn
      exposure: a negative impact on animal reproductive health.
AB  - Ametryn is an herbicide used to control broadleaf and grass weeds and its acute
      and chronic toxicity is expected to be low. Since toxicological data on ametryn
      is scarce, the aim of this study was to evaluate rat reproductive toxicity.
      Thirty-six adult male Wistar rats (90 days) were divided into three groups: Co
      (control) and T1 and T2 exposed to 15 and 30 mg/kg/day of ametryn, respectively,
      for 56 days. Testicular analysis demonstrated that ametryn decreased sperm number
      per testis, daily sperm production, and Leydig cell number in both treated
      groups, although little perceptible morphological change has been observed in
      seminiferous tubule structure. Lipid peroxidation was higher in group T2,
      catalase activity decreased in T1 group, superoxide dismutase activity
      diminished, and a smaller number of sulphydryl groups of total proteins were
      verified in both exposed groups, suggesting oxidative stress. These results
      showed negative ametryn influence on the testes and can compromise animal
      reproductive performance and survival. 

PMID- 25561258
TI  - Amine-functionalized mesoporous polymer as potential sorbent for nickel
      preconcentration from electroplating wastewater.
AB  - In this study, mesoporous glycidyl methacrylate-divinylbenzene-based chelating
      resin was synthesized and grafted with diethylenetriamine through epoxy ring
      opening reaction. The synthesized resin was characterized by elemental analysis,
      infrared spectroscopy, surface area and pore size analysis, scanning electron
      microscopy, energy-dispersive spectroscopy, and thermogravimetry. The resin was
      used for the first time as an effective sorbent for the preconcentration of
      nickel in electroplating wastewater samples. The analytical variables like pH,
      flow rate for sorption/desorption, and eluate selection were systematically
      investigated and optimized. The uniform and monolayer sorption behavior of resin
      for nickel was proved by an evident fit of the equilibrium data to a Langmuir
      isotherm model. Under optimized conditions, the resin was observed to show a good
      sorption capacity of 20.25 mg g(-1) and >96% recovery of nickel even in the
      presence of a large number of competitive matrix ions. Its ability to extract
      trace amount of nickel was exhibited by low preconcentration limit (5.9 MUg L(
      1)). The calibration curve was found to be linear (R(2) = 0.998) in the
      concentration range of 6.0-400.0 MUg L(-1). Coefficient of variation of less than
      5 for all the analysis indicated good reproducibility. The reliability was
      evaluated by the analysis of standard reference material (SRM) and recovery
      experiments. The applicability of the resin for the systematic preconcentration
      of nickel is substantiated by the analysis of electroplating wastewater and river
      water samples. Graphical abstract ?.

PMID- 25561259
TI  - Prediction of the sorption capacities and affinities of organic chemicals by XAD
      7.
AB  - Macro-porous resins are widely used as adsorbents for the treatment of organic
      contaminants in wastewater and for the pre-concentration of organic solutes from
      water. However, the sorption mechanisms for organic contaminants on such
      adsorbents have not been systematically investigated so far. Therefore, in this
      study, the sorption capacities and affinities of 24 organic chemicals by XAD-7
      were investigated and the experimentally obtained sorption isotherms were fitted
      to the Dubinin-Ashtakhov model. Linear positive correlations were observed
      between the sorption capacities and the solubilities (SW) of the chemicals in
      water or octanol and between the sorption affinities and the solvatochromic
      parameters of the chemicals, indicating that the sorption of various organic
      compounds by XAD-7 occurred by non-linear partitioning into XAD-7, rather than by
      adsorption on XAD-7 surfaces. Both specific interactions (i.e., hydrogen-bonding
      interactions) as well as nonspecific interactions were considered to be
      responsible for the non-linear partitioning. The correlation equations obtained
      in this study allow the prediction of non-linear partitioning using well-known
      chemical parameters, namely SW, octanol-water partition coefficients (KOW), and
      the hydrogen-bonding donor parameter (alpham). The effect of pH on the sorption
      of ionizable organic compounds (IOCs) could also be predicted by combining the
      correlation equations with additional equations developed from the estimation of
      IOC dissociation rates. The prediction equations developed in this study and the
      proposed non-linear partition mechanism shed new light on the selective removal
      and pre-concentration of organic solutes from water and on the regeneration of
      exhausted XAD-7 using solvent extraction.

PMID- 25561260
TI  - Uptake, effects, and regeneration of barley plants exposed to gold nanoparticles.
AB  - Within the last years, nanogold has become more and more important in
      nanotechnology, for example, as catalyst or in medical applications. Its rising
      production, application, and disposal inevitably lead to an increased emission of
      gold nanoparticles (Au-NPs) in the environment. However, only little is known
      about the uptake and effects of Au-NPs on biota. The objective of this study was
      to investigate the reversibility and effects of citrate-coated Au-NP uptake into
      the model organism barley (Hordeum vulgare L.). For this purpose, barley seeds
      were cultivated in Au-NP-containing nutrient solution for 2 weeks before the
      seedlings were transferred into Au-NP-free media and grown for another 3 weeks.
      Stability of Au-NPs in the cultivation media was investigated over the 2-week
      exposure time. Gold content in the leaves and roots of the plants was measured
      after 2 weeks of exposure and after 7, 14, and 21 days of regeneration by means
      of total reflection X-ray fluorescence (TXRF) analysis after microwave-assisted
      digestion. Moreover, Au-NPs within plant material were localized by transmission
      electron microscopy (TEM) of ultrathin cross sections. The obtained results
      reveal that Au-NPs accumulate in the plant roots. Concentration-dependent effects
      on the uptake of macronutrients and micronutrients, as well as on biomass
      production of exposed plants, in particular, on root growth were observed. Even
      though exposed barley plants were able to regenerate to a certain extent, their
      root growth was permanently decreased. 

PMID- 25561262
TI  - A survey of smart water quality monitoring system.
AB  - The smart water quality monitoring, regarded as the future water quality
      monitoring technology, catalyzes progress in the capabilities of data collection,
      communication, data analysis, and early warning. In this article, we survey the
      literature till 2014 on the enabling technologies for the Smart Water Quality
      Monitoring System. We explore three major subsystems, namely the data collection
      subsystem, the data transmission subsystem, and the data management subsystem
      from the view of data acquiring, data transmission, and data analysis.
      Specifically, for the data collection subsystem, we explore selection of water
      quality parameters, existing technology of online water quality monitoring,
      identification of the locations of sampling stations, and determination of the
      sampling frequencies. For the data transmission system, we explore data
      transmission network architecture and data communication management. For the data
      management subsystem, we explore water quality analysis and prediction, water
      quality evaluation, and water quality data storage. We also propose possible
      challenges and future directions for each subsystem. 

PMID- 25561261
TI  - Spatial distribution and partitioning of organophosphates pesticide in water and
      sediment from Sarno River and Estuary, Southern Italy.
AB  - The organophosphates pesticide (OPP) pollution in the Sarno River and its
      environmental impact on the Gulf of Naples (Tyrrhenian Sea, Central Mediterranean
      Sea) were estimated. Nine selected OPPs (diazinon, dimethoate, malathion,
      chlorpyrifos, dichlorvos, fenitrothion, methidathion, tolclofos-methyl, azinphos
      methyl) were determined in the water dissolved phase (DP), suspended particulate
      matter (SPM) and sediment samples. Total OPP concentrations ranged from 5.58 to
      39.25 ng L(-1) in water (as the sum of the DP and SPM) and from 0.19 to 3.98 ng
      g(-1) in sediment samples. Contaminant discharges of OPPs into the sea were
      calculated in about 48,064.08 g year(-1), showing that this river should account
      as one of the main contribution sources of OPPs to the Tyrrhenian Sea. 

PMID- 25561263
TI  - Simultaneous detection of perchlorate and bromate using rapid high-performance
      ion exchange chromatography-tandem mass spectrometry and perchlorate removal in
      drinking water.
AB  - Perchlorate and bromate occurrence in drinking water causes health concerns due
      to their effects on thyroid function and carcinogenicity, respectively. The
      purpose of this study was threefold: (1) to advance a sensitive method for
      simultaneous rapid detection of perchlorate and bromate in drinking water system,
      (2) to systematically study the occurrence of these two contaminants in Missouri
      drinking water treatment systems, and (3) to examine effective sorbents for
      minimizing perchlorate in drinking water. A rapid high-performance ion exchange
      chromatography-tandem mass spectrometry (HPIC-MS/MS) method was advanced for
      simultaneous detection of perchlorate and bromate in drinking water. The HPIC
      MS/MS method was rapid, required no preconcentration of the water samples, and
      had detection limits for perchlorate and bromate of 0.04 and 0.01 MUg/L,
      respectively. The method was applied to determine perchlorate and bromate
      concentrations in total of 23 selected Missouri drinking water treatment systems
      during differing seasons. The water systems selected include different source
      waters: groundwater, lake water, river water, and groundwater influenced by
      surface water. The concentrations of perchlorate and bromate were lower than or
      near to method detection limits in most of the drinking water samples monitored.
      The removal of perchlorate by various adsorbents was studied. A cationic
      organoclay (TC-99) exhibited effective removal of perchlorate from drinking water
      matrices. 

PMID- 25561265
TI  - Arsenic in coal of the Thar coalfield, Pakistan, and its behavior during
      combustion.
AB  - The aim of the current study is to evaluate the occurrence of arsenic in coal
      collected from Thar coalfield, Pakistan, and its behavior during the combustion.
      Fractionation of arsenic (As) in coal samples was carried out by Community Bureau
      of Reference sequential extraction scheme (BCR-SES) and single-step-based BCR
      method (BCR-SS). These methods are validated using the certified reference
      material of sediment BCR 701 and standard addition method. The stepwise fractions
      of As in laboratory-made ash (LMA) have been also investigated. The extractable
      As content associated with different phases in coal and LMA samples were analyzed
      by electrothermal atomic absorption spectrophotometer. The extraction efficiency
      of As by BCR-SS was slightly higher than BCR-SES, while the difference was not
      significant (p < 0.05). The BCR-SS method is a time-saving method because it can
      reduce the extraction time from 51 to 22 h. The As contents in LMA revealed that
      during combustion of the coal, >85 % of As may be released into atmosphere. The
      relative mobility of As in the coal samples was found in increasing order as
      follows: oxidizable fraction < reducible fraction < acid soluble fraction. The
      total and extractable As obtained by BCR-SES and BCR-SS were higher in coal
      samples of block III as compared to block V (p > 0.05). 

PMID- 25561264
TI  - Sorption-desorption behavior of pesticides and their degradation products in
      volcanic and nonvolcanic soils: interpretation of interactions through two-way
      principal component analysis.
AB  - Sorption-desorption behavior of six pesticides and some degradation products was
      assessed on seven agricultural volcanic and nonvolcanic soils belonging to
      Andisol, Ultisol, Mollisol, and Alfisol orders. The global interpretation of
      sorption data was performed by principal component analysis. Results showed
      exceptionally high sorption of glyphosate and aminomethylphosphonic acid (AMPA)
      (the breakdown product) on volcanic soils (K f > 1500 MUg(1 - 1 / n) mL(1 / n) g(
      1)) related mainly to contents of amorphous aluminum oxides (Andisols) and
      crystalline minerals (Ultisols). The lower sorption on nonvolcanic soils was
      associated to low organic matter contents and lack of significant minerals.
      Metsulfuron-methyl and 3,5,6-trichloro-2-pyridinol (metabolite of chlorpyrifos)
      were weakly to substantially sorbed on Andisols and Ultisols, but the first one
      was not sorbed at pH > 6.4, including nonvolcanic soils. The metabolite of
      diazinon, 2-isopropyl-4-methyl-6-hydroxypyrimidine, was weakly sorbed on all
      soils (K f = 0.4 to 3.6 MUg(1 - 1 / n) mL(1 / n) g(-1)). Acidic compounds would
      be lixiviated in Mollisols and Alfisols, but they could leach also in Andisols
      and Ultisols if they reach greater depths. Atrazine and deethylatrazine sorption
      was related to organic carbon content; therefore, they were weakly retained on
      nonvolcanic soils (K f = 0.7 to 2.2 MUg(1 - 1 / n) mL(1 / n) g(-1)). Chlorpyrifos
      was highly sorbed on all soils reaching K OC values of >8000. Finally, the
      significant retention of chlorothalonil and diazinon on Mollisols and Alfisols in
      spite of their low OC contents showed the contribution of clay minerals in the
      sorption process. 

PMID- 25561266
TI  - Behavior of ambient concentrations of natural radionuclides (7)Be, (210)Pb, (40)K
      in the Mediterranean coastal city of Malaga (Spain).
AB  - During a 4-year period (January 2009-December 2012), the (7)Be, (210)Pb, and
      (40)K activity concentrations in airborne particulate matter were weekly
      determined at the Malaga (Spain) located in the southern Iberian Peninsula.
      Totally 209 polypropylene filters were analyzed in the mentioned period. In 100%
      of the filters, (7)Be and (40)K activity concentrations were detected while
      (210)Pb activity concentration was detected in 96% of the filters. The results
      from individual measurements of (7)Be, (210)Pb, and (40)K concentrations were
      analyzed to derive the statistical estimates characterizing the distributions.
      Principal components analysis (PCA) was applied to the datasets and the results
      of the study reveal that aerosol behavior is represented by two principal
      components which explain 73.2% of total variance. Components PC1 and PC2
      respectively explain 46.0 and 27.2% of total variance. PC1 was related positively
      to dust content, (7)Be and (40)K concentrations and negatively to sunspot
      numbers. In contrast, PC2 was related positively to temperature and (210)Pb
      activity and negatively to precipitation and relative humidity. The (7)Be levels
      showed a significant correlation with sunspot numbers due to the cosmogenic
      origin. (40)K activities showed a good correlation with dust deposition in
      filters mainly because it was transported to the air as resuspended particle from
      the soil. An inverse relationship was observed between the (210)Pb concentrations
      and monthly rainfall, indicating washout of atmospheric aerosols carrying these
      radionuclides and a pronounced positive correlation with the average monthly
      temperature of air.

PMID- 25561267
TI  - Assessment of heavy metal contamination in the sediments from the Yellow River
      Wetland National Nature Reserve (the Sanmenxia section), China.
AB  - The Yellow River Wetland National Nature Reserve (the Sanmenxia section) is an
      important area of the Yellow River for two important hydrologic gauging stations:
      the Sanmenxia reservoir and the Xiaolangdi reservoir. Seven sites along the
      section were selected: Jiziling, Dinghuwan, Houdi, Canglonghu, Shangcun,
      Wangguan, and Nancun. After the microwave digestion with aqua regia,
      concentrations of Cu, Pb, Cd, Cr, Zn, and Mn in the sediments were analyzed by
      flame atomic absorption spectrometry with air-acetylene flame. The results showed
      that all the concentrations of Cr detected were from the lithogenic source, and
      63 % Mn, 48 % Pb, 41 % Cu, 20 % Cd, and 12 % Zn were from the anthropogenic
      source. The values of the index of geo-accumulation pointed out that there was
      moderate contamination of Mn at the Dinghuwan (1.04) and Houdi (1.00) sites
      (class 2), while the modified degree of contamination denoted that the
      contamination at the Houdi site (2.02) was moderate, nil to very low at the
      Nancun and Shangcun sites and low at the other sites, consisting with the
      tendency of pollution load index. For metal toxicity, the sediment pollution
      index indicated that the sediments of the Canglonghu site were low polluted, that
      of the Houdi site is nearly slightly contaminated, and those of others were
      natural and uncontaminated. It was vital to evaluate the degree of contamination
      with individual and overall elements and even with the metal toxicity. Cu, Pb,
      and Mn contaminations were aggravated in the Sanmenxia section, and there maybe
      was one of the main anthropogenic sources of these metals along the Yellow River.
      The findings were expected to update the current status of the heavy metal
      pollution in the Sanmenxia section as well as to create awareness concerning the
      sound condition of the whole reaches of the Yellow River. 

PMID- 25561268
TI  - Model development with defined biological mechanisms for xenobiotic treatment
      activated sludge at steady state.
AB  - Activated sludge treatment of a xenobiotic organic compound, much different from
      treatment of biogenic organics, must be modeled with interactions involving a two
      part biomass of degrader and nondegrader, which selectively or competitively grow
      on a two-part substrate of input xenobiotic and its biogenic metabolites. A
      xenobiotic treatment model was developed which incorporates kinetics of the
      growth of degrader and nondegrader, the line dividing metabolites into xenobiotic
      and biogenic, yields of degrader and nondegrader from utilization of their parts
      of substrates, and kinetics of degrader reversion to nondegrader due to
      instability of the degradative element degraders carry. Experimental activated
      sludge operated for treatment of a xenobiotic generated data for calibration of
      the model. With the input of influent xenobiotic concentration, mean cell and
      hydraulic residence times, and calibrated parameters, the model readily outputs
      concentrations of degrader, nondegrader, and effluent biogenic residue that
      closely match the results obtained from experiments. 

PMID- 25561269
TI  - Fluorine-decoupled carbon spectroscopy for the determination of configuration at
      fully substituted, trifluoromethyl- and perfluoroalkyl-bearing carbons:
      comparison with 19F-1H heteronuclear Overhauser effect spectroscopy.
AB  - The synthesis of a series of alpha-trifluoromethylcyclohexanols and analogous
      trimethylsilyl ethers by addition of the Ruppert-Prakash reagent to substituted
      cyclohexanones is presented. A method for the assignment of configuration of such
      compounds, of related alpha-trifluoromethylcyclohexylamines and of quaternary
      trifluoromethyl-substituted carbons is described based on the determination of
      the (3)J(CH) coupling constant between the fluorine-decoupled (13)CF3 resonance
      and the vicinal hydrogens. This method is dubbed fluorine-decoupled carbon
      spectroscopy and abbreviated FDCS. The method is also applied to the
      configurational assignment of substances bearing mono-, di-, and perfluoroalkyl
      rather than trifluoromethyl groups. The configuration of all substances was
      verified by either (19)F-(1)H heteronuclear Overhauser spectroscopy (HOESY) or X
      ray crystallography. The relative merits of FDCS and HOESY are compared and
      contrasted. (2)J(CH), (3)J(CH), and (4)J(CH) coupling constants to (19)F
      decoupled CF3 groups in alkenes and arenes have also been determined and should
      prove to be useful in the structural assignment of trifluoromethylated alkenes
      and arenes.

PMID- 25561270
TI  - MiR-101 inhibits cell growth and tumorigenesis of Helicobacter pylori related
      gastric cancer by repression of SOCS2.
AB  - Several microRNAs (miRNA) have been implicated in H. pylori related gastric
      cancer (GC). However, the molecular mechanism of miRNAs in gastric cancer has not
      been fully understood. In this study, we reported that miR-101 is significantly
      down-regulated in H. pylori positive tissues and cells and in tumor tissues with
      important functional consequences. Ectopic expression of miR-101 dramatically
      suppressed cell proliferation and colony formation by inducing G1-phase cell
      cycle arrest. We found that miR-101 strongly reduced the expression of SOCS2
      oncogene in GC cells. Similar to the restoring miR-26 expression, SOCS2 down
      regulation inhibited cell growth and cell-cycle progression, whereas SOCS2 over
      expression rescued the suppressive effect of miR-101. Mechanistic investigations
      revealed that miR-101 suppressed the expression of c-myc, CDK2, CDK4, CDK6,
      CCND2, CCND3, and CCNE2, while promoted tumor suppressor p14, p16, p21 and p27
      expression. In clinical specimens, SOCS2 was over-expressed in tumors and H.
      pylori positive tissues and its mRNA levels were inversely correlated with miR
      101 expression. Taken together, our results indicated that miR-101 functions as a
      growth-suppressive miRNA in H. pylori related GC, and that its suppressive
      effects are mediated mainly by repressing SOCS2 expression.

PMID- 25561271
TI  - Zinc Detoxification Is Required for Full Virulence and Modification of the Host
      Leaf Ionome by Xylella fastidiosa.
AB  - Zinc (Zn) is an essential element for all forms of life because it is a
      structural or catalytic cofactor of many proteins, but it can have toxic effects
      at high concentrations; thus, microorganisms must tightly regulate its levels.
      Here, we evaluated the role of Zn homeostasis proteins in the virulence of the
      xylem-limited bacterium Xylella fastidiosa, causal agent of Pierce's disease of
      grapevine, among other diseases. Two mutants of X. fastidiosa 'Temecula' affected
      in genes which regulate Zn homeostasis (zur) and Zn detoxification (czcD) were
      constructed. Both knockouts showed increased sensitivity to Zn at physiologically
      relevant concentrations and increased intracellular accumulation of this metal
      compared with the wild type. Increased Zn sensitivity was correlated with
      decreased growth in grapevine xylem sap, reduced twitching motility, and
      downregulation of exopolysaccharide biosynthetic genes. Tobacco plants inoculated
      with either knockout mutant showed reduced foliar symptoms and a much reduced
      (czcD) or absent (zur) modification of the leaf ionome (i.e., the mineral
      nutrient and trace element composition), as well as reduced bacterial
      populations. The results show that detoxification of Zn is crucial for the
      virulence of X. fastidiosa and verifies our previous findings that modification
      of the host leaf ionome correlates with bacterial virulence. 

PMID- 25561272
TI  - Sleep in adolescent depression: physiological perspectives.
AB  - Depression and disturbed sleep are intimately and bidirectionally related. During
      adolescence, the incidence of both insomnia and major depression increases
      simultaneously, in a gender-specific manner. The majority of depressed
      adolescents suffer from different types of subjective sleep complaints. Despite
      these complaints, the results from polysomnographic studies in depressed
      adolescents remain inconsistent. In general, similar features to those seen among
      adults with depressive disorder (e.g. abnormalities in rapid eye movement sleep
      and difficulties in sleep onset) have been reported, but expressed to a lesser
      degree. The inconsistency in findings may be linked with maturational factors,
      factors related to the stage of illness and greater heterogeneity in the clinical
      spectrum of depression among adolescents. The exact neurobiological mechanisms by
      which sleep alterations and depression are linked during adolescence are not
      fully understood. Aberrations in brain maturation, expressed at different levels
      of organization, for example gene expression, neurotransmitter and hormone
      metabolism, and activity of neuronal networks have been suggested. The circadian
      systems may change in adolescent depression beyond that observed during healthy
      adolescent development (i.e. beyond the typical circadian shift towards
      eveningness). A number of therapeutic approaches to alleviate sleep disruption
      associated with depression have been proposed, but research on the efficacy of
      these interventions in adolescents is lacking. Knowledge of the neurobiological
      links between sleep and depression during adolescence could lead to new insights
      into effective prevention and treatment of depression. 

PMID- 25561273
TI  - Movement disorders in 2014. Genetic advances spark a revolution in dystonia
      phenotyping.
AB  - Genetic revelations in 2014 are testing traditional classification systems for
      movement disorders, and our approach to clinical diagnostics. Mutations in
      dystonia-associated genes lead to a spectrum of disorders with different
      phenotypes, underscoring the need for stringent clinical phenotyping of patients
      with movement disorders, as well as next-generation sequencing approaches.

PMID- 25561274
TI  - Epilepsy in 2014. Novel and large collaborations drive advances in epilepsy.
AB  - In 2014, novel, large-scale collaborative efforts and frameworks resulted in
      major advances in the epilepsy field, from publication of a new definition of
      epilepsy to important discoveries regarding aetiology, pathophysiology and
      management. These collaborative works provide a platform from which further
      advances are anticipated, and a model for future research.

PMID- 25561276
TI  - Traumatic brain injury. No benefit of progesterone therapy in patients with TBI.

PMID- 25561277
TI  - Redox-active and DNA-binding coordination complexes of clotrimazole.
AB  - DNA interactions of anticancer mononuclear Cu(2+), Co(2+), Zn(2+), and Ni(2+)
      complexes with the biologically active ligand clotrimazole (clotri) are reported.
      To fully characterize DNA binding modes for these complexes of the formulae
      [M(clotri)2Cl2].nH2O (1-4), [M(clotri)2Br2].nH2O (5,6), [M(clotri)3NO3]NO3.nH2O
      (9), and [M(clotri)3(NO3)2] (10), circular dichroism (CD) and linear dichroism
      (LD) spectroscopy, UV melting experiments, atomic force microscopy (AFM) and
      ethidium bromide (EtBr) displacement methods were used. Results indicate mixed
      electrostatic interactions, possibly through groove binding, that result in
      accretion and coiling of DNA. Electrochemical studies indicate that the Cu(2+)
      complex 9 readily reduces to the reactive-oxygen-species-generating Cu(+), which
      oxidatively damages DNA. There is a subtle correlation between log P values,
      calculated electrostatic potentials, and cytotoxicity of the complexes. The
      extent of cell-nucleus DNA-metal adduct formation in the HeLa cervix-uterine
      carcinoma cell line does not necessarily correlate with cytotoxicity, indicating
      that the nature of DNA lesions may be crucial to activity.

PMID- 25561278
TI  - Chronic low back pain, chronic disability at work, chronic management issues.

PMID- 25561275
TI  - Intravenous immunoglobulin in neurology--mode of action and clinical efficacy.
AB  - Intravenous immunoglobulin (IVIg)-a preparation of polyclonal serum IgG pooled
      from thousands of blood donors-has been used for nearly three decades, and is
      proving to be an efficient anti-inflammatory and immunomodulatory treatment for a
      growing number of neurological diseases. Evidence from controlled clinical trials
      has established IVIg as a first-line therapy for Guillain-Barre syndrome, chronic
      inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. IVIg
      is also an effective rescue therapy in some patients with worsening myasthenia
      gravis, and is beneficial as a second-line therapy for dermatomyositis and stiff
      person syndrome. IVIg has been tested in some neurodegenerative disorders, but a
      controlled study in Alzheimer disease yielded disappointing results. Despite its
      widespread use and therapeutic success, the mechanisms of action of IVIg are
      poorly understood. Several hypotheses, based on the function of either the
      variable or constant IgG fragments, have been proposed to explain IVIg's
      immunomodulatory activity. This Review highlights emerging data on the mechanisms
      of action of IVIg related to its anti-inflammatory activity, especially that
      involving the cellular Fcgamma receptors and Fc glycosylation. We also summarize
      recent trials in neurological diseases, discuss potential biomarkers of efficacy,
      offer practical guidelines on administration, and provide a rationale for
      experimental trials in neuroinflammatory disorders. 

PMID- 25561279
TI  - Attenuation of the early events of alpha-synuclein aggregation: a fluorescence
      correlation spectroscopy and laser scanning microscopy study in the presence of
      surface-coated Fe3O4 nanoparticles.
AB  - The aggregation of alpha-synuclein (A-syn) has been implicated in the
      pathogenesis of Parkinson's disease (PD). Although the early events of
      aggregation and not the matured amyloid fibrils are believed to be responsible
      for the toxicity, it has been difficult to probe the formation of early oligomers
      experimentally. We studied the effect of Fe3O4 nanoparticle (NP) in the early
      stage of aggregation of A-syn using fluorescence correlation spectroscopy (FCS)
      and laser scanning microscopy. The binding between the monomeric protein and NPs
      was also studied using FCS at single-molecule resolution. Our data showed that
      the addition of bare Fe3O4 NPs accelerated the rate of early aggregation, and it
      did not bind the monomeric A-syn. In contrast, L-lysine (Lys)-coated Fe3O4 NPs
      showed strong binding with the monomeric A-syn, inhibiting the early events of
      aggregation. Lys-coated Fe3O4 NPs showed significantly less cell toxicity
      compared with bare Fe3O4 NPs and can be explored as a possible strategy to
      develop therapeutic application against PD. To the best of our knowledge, this
      report is the first example of using a small molecule to attenuate the early (and
      arguably the most relevant in terms of PD pathogenesis) events of A-syn
      aggregation.

PMID- 25561281
TI  - Therapeutic Value of Blood Purification and Prognostic Utilities of Early Serum
      Procalcitonin, C Reactive Protein, and Brain Natriuretic Peptide Levels in
      Severely Burned Patients with Sepsis.
AB  - The objective of this study was to evaluate therapeutic effectiveness of blood
      purification (BP) in severely burned patients with sepsis and to assess the
      prognostic utilities of early serum levels of procalcitonin (PCT), C reactive
      protein (CRP), brain natriuretic peptide (BNP). One hundred and ninety-five burn
      sepsis patients admitted in our hospital during May, 2008-May, 2014 were selected
      for the study and randomly divided into BP treatment (n = 98) and the control
      groups (n = 97). All of these patients received conventional therapy, while the
      BP group underwent additional BP treatment. Therapeutic effectiveness and
      survival rates of the two groups were compared 28 days after the treatment. The
      BP group was further divided into survivor and mortality groups, and the early
      serum levels of PCT, CRP, and BNP were compared retrospectively to analyze their
      relationship with prognosis. Acute physiology and chronic health evaluation and
      sequential organ failure assessment scores in the two groups were not
      significantly different before the treatment (p > 0.05). However, after the
      treatment, mortality in BP group (19.39 %) was significantly lower (p < 0.05)
      than that of the controls (27.84 %). Serum levels of PCT and CRP in the survivor
      and mortality groups were not significantly different (p > 0.05), whereas the
      serum BNP was significantly lower in the patients who survived than those who
      died (p < 0.05). The receiver-operating characteristic curve analysis further
      showed that predictive value of PCT and CRP for the burn sepsis prognosis was low
      (p > 0.05), however, that of the BNP was good (p < 0.05). The results obtained in
      this study indicate that BP treatment at an early stage can significantly improve
      the prognosis of burn sepsis. Furthermore, BNP, an important mediator involved in
      myocardial infarction and heart failure was found to be positively related with
      the severity of sepsis suggesting its reliable utility as prognostic indicator of
      sepsis. Thus, serum BNP monitored during the treatment may assist in adjusting
      the therapeutic strategies.

PMID- 25561280
TI  - Comparison of the Outcomes of Two Operational Methods Used for the Fixation of
      Calcaneal Fracture.
AB  - This study was aimed to compare the outcomes of two operational methods used for
      the fixation of calcaneal fracture, the open reduction using a plate and the
      minimally invasive cannulated screw fixations. Thus, we attempted to find out as
      to which of these fixation regimens was therapeutically superior by assessing
      improvement in the restoration of foot functioning and estimating the biochemical
      indices that reflect bone recovery. A total of 492 calcaneal fracture patients
      admitted in our hospital from February, 2008 to February, 2012 were selected for
      the study and randomly divided into two groups of 246 cases each. They were
      treated with either open reduction using a plate or minimally invasive cannulated
      screw fixation procedures. After the operations, patients were followed up for 2
      years and the outcomes including functional restoration of calcaneus, the post
      operational complications, and measure of the biochemical indicators of bone
      recovery were compared. The patients who underwent plate fixation procedure
      showed the excellent and good rate of 76.8 %. The minimally invasive cannulated
      screw fixation led to the excellent and good rate of 82.5 %. The angle, width,
      and height of calcaneus observed in the last follow-up were also improved
      significantly in the two groups (p < 0.05); however, these outcomes of the two
      techniques were not significantly different from each other (p > 0.05). The post
      operative complications occurred with the rates of 14.2 and 4.9 % in the patients
      treated with the plate and the minimally invasive cannulated screw fixations,
      respectively. The length of stay and hospitalization costs in the plate fixation
      group were 9.16 +/- 0.83 days and 12,639.74 +/- 2,573.82 Chinese Yuan,
      respectively. In comparison, in cannulated screw fixation group, the length of
      hospital stay (7.03 +/- 0.52 days) and its cost (6,795.01 +/- 996.53 Chinese
      Yuan) were significantly lower. Serum bone alkaline phosphatase and tartrate
      resistant acid phosphatase-5b levels measured at the last follow-up examination
      were significantly altered (p < 0.05) in the two groups. However, the difference
      between the outcomes of the two methods was not statistically significant (p >
      0.05). Plate screw and the cannulated screw fixations showed equally good
      therapeutic effect and significantly improved patients' mobility. However, the
      cannulated screw fixation was superior in terms of post-operative infection-free
      recovery and economical burden to the patients.

PMID- 25561282
TI  - Transglutaminase-2 is Involved in Cell Apoptosis of Osteosarcoma Cell Line U2OS
      Under Hypoxia Condition.
AB  - Osteosarcoma is the most common type of solid bone cancer, which is the second
      leading cause of cancer-related death. Hypoxia is an ordinary phenomenon in solid
      tumor tissues and can induce cell apoptosis but the specific molecular mechanism
      remains unclear. In this study, we explored the effect and the molecular
      mechanism of Transglutaminase 2 (TG2) on cell apoptosis in osteosarcoma U2OS
      cells under hypoxia. We found the enzymatic activity of TG2 is significantly
      increased and the expression of TG2 is remarkably up-regulated under hypoxia
      condition. Cell apoptotic rate is markedly increased upon knockdown of TG2 by
      siRNA under hypoxia. We further investigated the mechanism of cell apoptosis and
      found Bax protein is significantly increased after depletion of TG2 under
      hypoxia. Moreover, our data also show that cytochrome C (Cyt C) is significantly
      increased in cytoplasm and markedly decreased in mitochondria of U2OS cells after
      depletion of TG2 under hypoxia. Our results suggest that TG2 can inhibit tumor
      cell apoptosis through down-regulation of Bax and prevention of release Cyt C
      from mitochondria into cytoplasm. 

PMID- 25561283
TI  - HMGB1 Silencing Potentiates the Anti-inflammatory Effects of Sodium Ferulate in
      ox-LDL-Stimulated Vascular Smooth Muscle Cells.
AB  - Atherosclerosis is a sustained inflammatory disease of the arterial wall. The
      purpose of the current study is to investigate the effect of sodium ferulate on
      the proliferation and migration of human vascular smooth muscle cells (hVSMCs).
      In addition, we also sought to determine whether HMGB1 knockdown could potentiate
      the anti-inflammatory effects of sodium ferulate. hVSMCs were treated with
      oxidized lower-density lipoprotein (ox-LDL, 50 mg/l) to induce inflammation.
      Cells were then treated with sodium ferulate and HMGB1 silencing (SiHMGB1)
      individually or in combination. The phenotypes of the treated cells including
      proliferation, cell cycle profile, apoptosis, and gene expression were analyzed.
      Results showed that sodium ferulate or SiHMGB1 treatment inhibited ox-LDL-induced
      inflammation in hVSMCs. Furthermore, the combination of SiHMGB1 plus sodium
      ferulate treatment displayed an additive effect in inhibiting the proliferation
      and migration of hVSMCs. Consistently, the suppression of receptor for advanced
      glycation end products expression was also observed. ICAM-1 and transforming
      growth factor-beta suggest that these signaling components were involved in the
      anti-inflammatory effect. Our study confirms the anti-inflammatory function of
      sodium ferulate, and uncovered the potentiating effect of HMGB1 knockdown in
      suppressing ox-LDL-induced proliferation and migration of hVSMCs. Inhibition of
      HMGB1 expression in addition to sodium ferulate treatment might be a more
      effective therapeutic approach for atherosclerosis.

PMID- 25561284
TI  - Ginsenoside Rh2 Targets EGFR by Up-Regulation of miR-491 to Enhance Anti-tumor
      Activity in Hepatitis B Virus-Related Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most aggressive tumors in humans.
      The typical therapeutic strategies include a combination of chemotherapy,
      radiotherapy, and surgery, whereas the survival rate of patients is very poor.
      Ginsenoside Rh2 has been reported to have therapeutic effects on some tumors, but
      its effect on HCC has not been extensively evaluated. Here, we show that
      ginsenoside Rh2 can effectively inhibit the proliferation and cell survival of
      HCC cells in vitro and in a mouse model. Moreover, the inhibition of the tumor
      growth appears to result from combined effects on decreased tumor cell
      proliferation and cell viability. Further analyses suggest that ginsenoside Rh2
      may have its anti-tumor effect through inhibition of epidermal growth factor
      receptor (EGFR) signaling pathway. Recombinant EGFR was given together with
      ginsenoside Rh2 to the tumor cells, which completely blocked the anti-tumor
      effect of ginsenoside Rh2. Our data also show that miR-491 is up-regulated in
      SMMC-7721 cells after Rh2 treatment. There is a negative correlation between EGFR
      and miR-491 levels in SMMC-7721 cells and miR-491 directly targeted EGFR at
      translational level. Our data not only reveal an anti-tumor effect of ginsenoside
      Rh2 but also demonstrate that this effect may function via activation and
      inhibition of EGFR signaling in HCC cells. The results suggest miR-491 can be a
      promising regulatory factor in EGFR signal transduction. 

PMID- 25561286
TI  - Liposome-Adenoviral hTERT-siRNA Knockdown in Fibroblasts from Keloids Reduce
      Telomere Length and Fibroblast Growth.
AB  - Keloids, which possess invasive tumor-like behavior, have been clinically
      challenging to clinicians especially surgeons. Excessive extracellular matrix
      secreted from fibroblasts is the main histo-pathological feature of keloids. In
      this study, we transfected hTERT-siRNA into scar fibroblasts by liposome
      adenoviral transduction in order to disrupt telomere length homeostasis and
      influence the cell cycle of fibroblasts. Our results showed that liposome hTERT
      siRNA was able to knock down hTERT gene expression in scar fibroblasts. Moreover,
      the telomerase activity in hTERT-siRNA group was significantly reduced compared
      with the control groups. And the telomeric length of hTERT-siRNA group was
      significantly shortened as well. Further, flow cytometry studies and MTT assay
      demonstrated that apoptosis rate of fibroblasts in liposome hTERT-siRNA group
      significantly increased. These results indicated that the liposome-mediated hTERT
      gene transduction could inhibit the growth of fibroblasts in scar tissues
      suggesting a promising strategy of keloids treatment in the future. 

PMID- 25561285
TI  - P2X2 and P2X5 Receptors Mediate Bladder Hyperesthesia in ICC in Female Overactive
      Bladder.
AB  - This study was set to explore the role of P2X2 and P2X5 as the important
      molecules in sensory afferent of bladder in female overactive bladder (OAB)
      patients with the bladder hyperesthesia. Sixty-eight OAB patients admitted in
      Southwest Hospital affiliated to the Third Military Medical University during
      September, 2011-December, 2012 were selected and included in the experimental
      group (OAB group) and 30 healthy volunteers during the same period were included
      as the control group. We recorded voiding diary and urodynamic results, and
      immunohistochemistry analysis was used to detect P2X2 and P2X5 receptor in
      interstitial cell of Caja (ICC) in bladder tissue of female OAB patients and
      healthy volunteers, to tentatively explore the effect of P2X2 and P2X5 in bladder
      hyperesthesia. Urodynamic study has important diagnostic value in the diagnosis
      and differential diagnosis of OAB. P2X2 receptor was significantly up-regulated
      in bladder ICC in OAB group. The blockage of P2X2 receptor could significantly
      inhibit the contraction of bladder muscle strips, decrease the bladder pressure
      and the electric discharge of pelvic nerve. PET and urodynamic study showed that
      micturition desire sense in PAG area of pons in OAB patients was significantly
      increased compared with the control group. The up-regulation of P2X2 in ICC is an
      important factor to cause bladder hyperesthesia in OAB patients. PET and
      urodynamic study indicate that the bladder-originated nervous impulses are
      important cause of OAB. This study provides a basis for the study of P2X2
      receptor in ICC in bladder hyperesthesia of OAB patients. 

PMID- 25561287
TI  - Apoptotic Effect of Koumine on Human Breast Cancer Cells and the Mechanism
      Involved.
AB  - Koumine is an alkaloid separated from traditional Chinese herb Gelsemium elegans.
      In this study, anticancer activity and underlying mechanisms were investigated
      with an extract using human breast cancer cells. The survival rate was reduced in
      a concentration- and time-dependent manner as assessed by MTT assay. After
      incubation for 48 h, typical apoptotic morphological changes were observed by
      Hoechst 33258 dye assay. Flow cytometry result revealed that the treatment
      obviously induced G2/M arrest and apoptosis in MCF-7 cells. Furthermore, Western
      blotting demonstrated the down-regulation of protein expression of Bcl-2, whereas
      Bax and caspase-3 expressions were up-regulated. Therefore, we propose that
      koumine has the potential to be a future breast cancer chemotherapeutic agent. 

PMID- 25561288
TI  - Construction of 2,4,6-Trinitrotoluene Biosensors with Novel Sensing Elements from
      Escherichia coli K-12 MG1655.
AB  - Detection of 2,4,6-trinitrotoluene (TNT) has been extensively studied since it is
      a common explosive filling for landmines, posing significant threats to the
      environment and human safety. The rapid advances in synthetic biology give new
      hope to detect such toxic and hazardous compounds in a more sensitive and safe
      way. Biosensor construction anticipates finding sensing elements able to detect
      TNT. As TNT can induce some physiological responses in E. coli, it may be useful
      to define the sensing elements from E. coli to detect TNT. An E. coli MG1655
      genomic promoter library containing nearly 5,400 elements was constructed. Five
      elements, yadG, yqgC, aspC, recE, and topA, displayed high sensing specificity to
      TNT and its indicator compounds 1,3-DNB and 2,4-DNT. Based on this, a whole cell
      biosensor was constructed using E. coli, in which green fluorescent protein was
      positioned downstream of the five sensing elements via genetic fusion. The
      threshold value, detection time, EC200 value, and other aspects of five sensing
      elements were determined and the minimum responding concentration to TNT was 4.75
      mg/L. According to the synthetic biology, the five sensing elements enriched the
      reservoir of TNT-sensing elements, and provided a more applicable toolkit to be
      applied in genetic routes and live systems of biosensors in future. 

PMID- 25561290
TI  - Decreased aggression and increased repetitive behavior in Pten haploinsufficient
      mice.
AB  - Aggression is an aspect of social behavior that can be elevated in some
      individuals with autism spectrum disorder (ASD) and a concern for peers and
      caregivers. Mutations in Phosphatase and tensin homolog (PTEN), one of several
      ASD risk factors encoding negative regulators of the PI3K-Akt-mTOR pathway, have
      been reported in individuals with ASD and comorbid macrocephaly. We previously
      showed that a mouse model of Pten germline haploinsufficiency (Pten(+/-) ) has
      selective deficits, primarily in social behavior, along with broad overgrowth of
      the brain. Here, we further examine the social behavior of Pten(+/-) male mice in
      the resident-intruder test of aggression, using a comprehensive behavioral
      analysis to obtain an overall picture of the agonistic, non-agonistic and non
      social behavior patterns of Pten(+/-) mice during a free interaction with a novel
      conspecific. Pten(+/-) male mice were involved in less aggression than their wild
      type littermates. Pten(+/-) mice also performed less social investigation,
      including anogenital investigation and approaching and/or attending to the
      intruder, which is consistent with our previous finding of decreased sociability
      in the social approach test. In contrast to these decreases in social behaviors,
      Pten(+/-) mice showed increased digging. In summary, we report decreased
      aggression and increased repetitive behavior in Pten(+/-) mice, thus extending
      our characterization of this model of an ASD risk factor that features brain
      overgrowth and social deficits. 

PMID- 25561289
TI  - Tet1-mediated DNA demethylation regulates neuronal cell death induced by
      oxidative stress.
AB  - Epigenetic regulations including DNA methylation and demethylation play critical
      roles in neural development. However, whether DNA methylation and demethylation
      may play a role in neuronal cell death remains largely unclear. Here we report
      that the blockade of DNA methyltransferase inhibits apoptosis of cerebellar
      granule cells and cortical neurons in response to oxidative stress. We found that
      knockdown of ten-eleven translocation methylcytosine dioxygenase (Tet1), a
      critical enzyme for DNA demethylation, significantly increase apoptosis of
      cerebellar granule cells induced by hydrogen peroxide. Moreover, cerebellar
      granule cells from tet1(null) mice appeared to be more sensitive to oxidative
      stress, suggesting the critical role of Tet1 in neuronal cell death. We further
      showed that the expression of Klotho, an antiaging protein, in cerebellar granule
      cells is tightly regulated by DNA methylation. Finally, we found that knockdown
      of Klotho diminished the rescue effects of DNA methyltransferase inhibitors and
      Tet1 on neuronal cell death induced by oxidative stress. Our work revealed the
      role of Tet1-mediated DNA demethylation on neuronal protection against oxidative
      stress and provided the molecular mechanisms underlying the epigenetic regulation
      of neuronal cell death, suggesting the role of Klotho in regulating neuronal cell
      death in response to oxidative stress. 

PMID- 25561292
TI  - Volumetric alterations in the heteromodal association cortex in children with
      autism spectrum disorder.
AB  - BACKGROUND: We investigated if alterations in higher-order association areas
      related to schizophrenia, namely the heteromodal association cortex (HASC), are
      also observable in subjects with autism spectrum disorder (ASD). METHODS: A group
      of 18 children with ASD and 18 healthy controls (HC) underwent magnetic resonance
      imaging (MRI). The examination comprised an analysis of group differences in gray
      matter (GM) volume, surface area (SA) and hemispheric lateralization. RESULTS:
      Differences in GM volumes in children with ASD and HC were detected in frontal
      and parietal areas related to the HASC. No HASC structure that showed changes in
      GM volume exhibited differences in SA. Alterations in hemispheric lateralization
      between ASD and HC are seen in a frontal area of the HASC. CONCLUSIONS: Our
      results indicate that changes in HASC areas are not restricted to schizophrenia,
      but extend to other psychiatric disorders, namely ASD. The lacking group
      differences in SA indicate that changes in GM volume are possibly evoked by other
      variables than SA in children with ASD.

PMID- 25561294
TI  - Cloning and tissue expression profiling of the GnRHR gene of the Muscovy duck
      (Cairina moschata): polymorphism and association with egg-laying performance.
AB  - 1. cDNA sequence of gonadotropin-releasing-hormone receptor (GnRHR) gene was
      cloned and an association analysis between mutations and laying performance was
      conducted. 2. A 1680-bp cDNA sequence of Muscovy duck GnRHR, which encodes 415
      amino acids, was obtained and characterised. Phylogenetic analysis revealed that
      Muscovy duck GnRHR has a close relationship with Gallus gallus GnRHR. 3. There
      were significantly different expression profiles between 4 age periods in the
      hypothalamus, pituitary, and ovary. The expression of GnRHR at the age of 36
      weeks (laying period) was higher than other time points in the three tissues.
      GnRHR was expressed in 12 different tissues. The highest expression levels were
      observed in hypothalamus, pituitary and gonads. 4. A single nucleotide
      polymorphism detected in the second intron was associated with egg-laying
      performance. Individuals with genotype TT had better egg-laying performance from
      individuals with genotypes CC or TC. Therefore, GnRHR could be used as a marker
      gene for laying performance in Muscovy duck. 

PMID- 25561293
TI  - Vitamin D3 as a novel regulator of basic fibroblast growth factor in chronic
      rhinosinusitis with nasal polyposis.
AB  - BACKGROUND: The immunopathogenesis of chronic rhinosinusitis (CRS) is largely
      unknown, but it is thought that different inflammatory profiles are responsible
      for the different CRS subtypes. 25-Hydroxyvitamin-D (25-VD3) has been shown to
      alter inflammatory mediators in other disease processes and 25-VD3 deficiency is
      associated with CRS with nasal polyps (CRSwNP), but it is unknown if 25-VD3
      levels impact local inflammation in CRS. This study investigated the correlation
      between plasma 25-VD3 and sinonasal mucus monocyte chemoattractant protein-1 (MCP
      1), regulated upon activation normal T cell expressed and secreted (RANTES), and
      basic fibroblast growth factor (bFGF) levels in patients with CRS. METHODS: Study
      subjects undergoing endoscopic sinus surgery (ESS) for CRS were prospectively
      enrolled from January 2012 to August 2014. Control subjects included patients
      undergoing ESS for noninflammatory pathology. Blood and sinonasal mucus were
      collected at the time of ESS. Plasma 25-VD3 was measured by enzyme-linked
      immunosorbent assay (ELISA) and mucus levels of MCP-1, RANTES, and bFGF by
      cytometric bead array (CBA). RESULTS: A total of 57 patients were enrolled and
      categorized as CRS without nasal polyps (CRSsNP) (n = 31), CRSwNP (n = 14), and
      controls (n = 12). No significant correlation was found between MCP-1 and 25-VD3.
      There was a significant negative correlation between 25-VD3 and RANTES (r = 
      0.612; p = 0.026) and bFGF (r = -0.578; p = 0.039) in CRSwNP patients; however,
      there was no significant correlation in CRSsNP patients. CONCLUSION: This data
      suggests that 25-VD3 may play a role in regulation of RANTES and bFGF expression
      in CRSwNP. This may occur through regulation of NP fibroblasts or other immune
      cells. Further investigation is warranted to better elucidate the role of RANTES,
      bFGF, and 25-VD3 in CRSwNP.

PMID- 25561291
TI  - Abnormalities in cortical gray matter density in borderline personality disorder.
AB  - BACKGROUND: Borderline personality disorder (BPD) is a chronic condition with a
      strong impact on patients' affective, cognitive and social functioning.
      Neuroimaging techniques offer invaluable tools to understand the biological
      substrate of the disease. We aimed to investigate gray matter alterations over
      the whole cortex in a group of Borderline Personality Disorder (BPD) patients
      compared to healthy controls (HC). METHODS: Magnetic resonance-based cortical
      pattern matching was used to assess cortical gray matter density (GMD) in 26 BPD
      patients and in their age- and sex-matched HC (age: 38 +/- 11; females: 16, 61%).
      RESULTS: BPD patients showed widespread lower cortical GMD compared to HC (4%
      difference) with peaks of lower density located in the dorsal frontal cortex, in
      the orbitofrontal cortex, the anterior and posterior cingulate, the right
      parietal lobe, the temporal lobe (medial temporal cortex and fusiform gyrus) and
      in the visual cortex (P<0.005). Our BPD subjects displayed a symmetric
      distribution of anomalies in the dorsal aspect of the cortical mantle, but a
      wider involvement of the left hemisphere in the mesial aspect in terms of lower
      density. A few restricted regions of higher density were detected in the right
      hemisphere. All regions remained significant after correction for multiple
      comparisons via permutation testing. CONCLUSIONS: BPD patients feature specific
      morphology of the cerebral structures involved in cognitive and emotional
      processing and social cognition/mentalization, consistent with clinical and
      functional data.

PMID- 25561295
TI  - Synthesis of novel boron chelate complexes and proposed mechanism of new
      rearrangement.
AB  - We synthesized novel boron chelate complexes by the reaction of pyrazoline
      derivatives and boron trifluoride diethyl etherate followed by a new
      rearrangement. The structures of the compounds were characterized by IR, NMR and
      HRMS, especially, a typical compound 3c was confirmed by X-ray single crystal
      analysis. We proposed a mechanism of the rearrangement. Moreover, the absorption
      and fluorescence spectroscopy of these compounds were measured. 

PMID- 25561296
TI  - Study of the interactivity between mercury and cellular system labeled with
      carboxymethyl chitosan-coated quantum dots and its application in a real-time in
      situ detection of mercury.
AB  - In this study, canine kidney cells (MDCK) are fluorescently labeled by
      carboxymethyl chitosan-coated CdTe quantum dots to obtain a stable fluorescence.
      Fluorescently labeled MDCK cells are incubated with Hg(2+) and passed flow
      cytometer to measure the mean fluorescence intensity, which shows [Hg(2+)] has a
      prominent quenching ability on the cells' fluorescence. The dose-dependent
      relation can be described by Stern-Volmer equation at the concentration range of
      5-70 MUg/L [Hg(2+)]. This method can be employed to determine the concentration
      of Hg(2+) in living cells by measuring the changes in fluorescence of the
      cellular system. The results show a relative standard deviation of 7.16% (n=11)
      and a recovery rate ranging from 92% to 103%, indicating a promising prospect of
      application on real-time in-situ analysis of [Hg(2+)] and its cytotoxic effects.

PMID- 25561297
TI  - Near-infrared reflectance spectroscopy (NIRS) for rapid determination of
      ginsenoside Rg1 and Re in Chinese patent medicine Naosaitong pill.
AB  - Ginsenosides in plant samples have been extensively studied because
      protopanaxadiol saponins are ubiquitous in Chinese patent medicines, in which
      they can be used in promoting human health as the main active ingredients. A
      method for rapid determination of two ginsenosides (Rg1 and Re) in Naosaitong
      (NST) samples using near-infrared reflectance spectroscopy (NIRS) is studied to
      determine the contents of ginsenoside Rg1 and Re in this work. Partial least
      square (PLS) regression was used for building the calibration models, and the
      effects of spectral preprocessing and variable selection on the models are
      investigated for optimization of the models. A total of 93 samples were scanned
      by NIRS, and also by high performance liquid chromatography coupled to a diode
      array detector to determine the contents of ginsenoside Rg1 and Re. The
      calibration models for Rg1 and Re had high values of the coefficient of
      determination (R(2)) (0.9766 and 0.9764) and low root mean square error of cross
      validation (RMSECV) (0.0136 and 0.0104), and the values of the standard error of
      prediction set (SEP) are 0.00764 and 0.0103, which indicate a good correlation
      between reference values and NIRS predicted values. The overall results show that
      NIRS could be applied for the rapid determination of the contents of ginsenosides
      in Ginseng byproducts for pharmaceuticals that develop high-quality Chinese
      patent medicines. 

PMID- 25561298
TI  - Green synthesis of silver nanoparticles using Croton sparsiflorus morong leaf
      extract and their antibacterial and antifungal activities.
AB  - Biologically synthesized nanoparticles have been widely used in the field of
      medicine. Especially, silver nanoparticles (Ag NPs) synthesized by the leaf
      extract lead the biological activity. In the present work, the synthesized Ag NPs
      by using the leaf extract of Croton sparsiflorus morong Ag NPs were characterized
      by using UV-Visible (UV-Vis) absorption spectroscopy, X-ray diffraction (XRD),
      Field Emission Scanning Electron Microscopy (FE-SEM) along with Energy Dispersive
      X-ray (EDX) Spectroscopy and Fourier Infrared (FT-IR) Spectroscopy, respectively.
      UV-Vis peak at 457 nm confirmed the Ag NPs due to the absorption. Cubic
      structural analysis and 16 nm particle size of the Ag NPs were calculated by
      using XRD analysis. The surface morphology along with the presence of Ag NPs was
      identified by using FE-SEM and EDX, respectively. The FT-IR study revealed with
      the functional groups of the Ag NPs. Finally, the present research has been
      explored to exhibit the significant antimicrobial activities.

PMID- 25561299
TI  - Validated spectrophotometric methods for simultaneous determination of troxerutin
      and carbazochrome in dosage form.
AB  - Four simple, accurate, sensitive and precise spectrophotometric methods were
      developed and validated for simultaneous determination of Troxerutin (TXN) and
      Carbazochrome (CZM) in their bulk powders, laboratory prepared mixtures and
      pharmaceutical dosage forms. Method A is first derivative spectrophotometry
      (D(1)) where TXN and CZM were determined at 294 and 483.5 nm, respectively.
      Method B is first derivative of ratio spectra (DD(1)) where the peak amplitude at
      248 for TXN and 439 nm for CZM were used for their determination. Method C is
      ratio subtraction (RS); in which TXN was determined at its lambdamax (352 nm) in
      the presence of CZM which was determined by D(1) at 483.5 nm. While, method D is
      mean centering of the ratio spectra (MCR) in which the mean centered values at
      300 nm and 340.0 nm were used for the two drugs in a respective order. The two
      compounds were simultaneously determined in the concentration ranges of 5.00
      50.00 MUg mL(-1) and 0.5-10.0 MUg mL(-1) for TXN and CZM, respectively. The
      methods were validated according to the ICH guidelines and the results were
      statistically compared to the manufacturer's method.

PMID- 25561300
TI  - Analysis of polycyclic aromatic hydrocarbons in water with gold nanoparticles
      decorated hydrophobic porous polymer as surface-enhanced Raman spectroscopy
      substrate.
AB  - A method for surface-enhanced Raman spectroscopy (SERS) sensing of polycyclic
      aromatic hydrocarbons (PAHs) is reported. Gold nanoparticles (AuNPs) decorated
      hydrophobic porous glycidyl methacrylate-ethylene dimethacrylate (GMA-EDMA)
      polymer is developed as the SERS substrate. GMA-EDMA material with porosity and
      permeability shows rapid and efficient adsorption of PAHs through presumed
      hydrophobic interaction, which brings the analytes close to the substrate.
      Meanwhile, the three dimensional porous morphology might benefit AuNPs
      distribution for high SERS enhancement. Studies on the effects of AuNPs surface
      coverage on the substrate and time of PAHs-substrate interaction are presented.
      The qualitative analysis and quantitative tendency of this method for PAHs
      detection are investigated with anthracene, phenanthrene and pyrene as probe
      molecules, showing that the characteristic fingerprint vibrational peaks of each
      PAH can be readily identified, and the limit of detections are 0.93*10(-7),
      4.5*10(-7) and 1.1*10(-7) M respectively. Moreover, the substrate exhibits high
      reproducibility with the relative standard deviation about 16% in spot and spot
      SERS intensity. Using this method for rapid screening of PAHs mixture in some
      water samples are performed well, which might be useful for environmental
      pollutions monitoring.

PMID- 25561301
TI  - Dansyl-labeled anionic amphiphile with a hexadecanoic carbon chain: synthesis and
      detection for shape transitions in organized molecular assemblies.
AB  - The probing properties of a new fluorophore-labeled anionic surfactant, sodium 16
      (N-dansyl)aminocetylate (16-DAN-ACA) were investigated systematically in
      molecular assemblies, especially in the transitions between micelles and
      vesicles. 16-DAN-ACA can efficiently differentiate the two different aggregate
      types in mixed cationic and anionic surfactant systems. The fluorescence
      anisotropy of 16-DAN-ACA was found to be sensitive for directly detecting the
      micellar growth in micelles containing oppositely charged surfactants; both
      cationic cetyltrimethylammonium bromide (CTAB) systems and anionic sodium dodecyl
      sulfate (SDS) systems were studied. The results indicated that the 16-DAN-ACA is
      a good fluorescent probe for differentiating the different aggregates, and even
      more can be used to detect the micellar growth. 

PMID- 25561302
TI  - Electronic [UV-Visible] and vibrational [FT-IR, FT-Raman] investigation and NMR
      mass spectroscopic analysis of terephthalic acid using quantum Gaussian
      calculations.
AB  - In this research work, the vibrational IR, polarization Raman, NMR and mass
      spectra of terephthalic acid (TA) were recorded. The observed fundamental peaks
      (IR, Raman) were assigned according to their distinctiveness region. The hybrid
      computational calculations were carried out for calculating geometrical and
      vibrational parameters by DFT (B3LYP and B3PW91) methods with 6-31++G(d,p) and 6
      311++G(d,p) basis sets and the corresponding results were tabulated. The
      molecular mass spectral data related to base molecule and substitutional group of
      the compound was analyzed. The modification of the chemical property by the
      reaction mechanism of the injection of dicarboxylic group in the base molecule
      was investigated. The (13)C and (1)H NMR spectra were simulated by using the
      gauge independent atomic orbital (GIAO) method and the absolute chemical shifts
      related to TMS were compared with experimental spectra. The study on the
      electronic and optical properties; absorption wavelengths, excitation energy,
      dipole moment and frontier molecular orbital energies, were performed by hybrid
      Gaussian calculation methods. The orbital energies of different levels of HOMO
      and LUMO were calculated and the molecular orbital lobe overlapping showed the
      inter charge transformation between the base molecule and ligand group. From the
      frontier molecular orbitals (FMO), the possibility of electrophilic and
      nucleophilic hit also analyzed. The NLO activity of the title compound related to
      Polarizability and hyperpolarizability were also discussed. The present molecule
      was fragmented with respect to atomic mass and the mass variation depends on the
      substitutions have also been studied. 

PMID- 25561303
TI  - Novel carbazole derivatives with quinoline ring: synthesis, electronic
      transition, and two-photon absorption three-dimensional optical data storage.
AB  - We designed carbazole unit with an extended pi conjugation by employing Vilsmeier
      formylation reaction and Knoevenagel condensation to facilitate the functional
      groups of quinoline from 3- or 3,6-position of carbazole. Two compounds doped
      with poly(methyl methacrylate) (PMMA) films were prepared. To explore the
      electronic transition properties of these compounds, one-photon absorption
      properties were experimentally measured and theoretically calculated by using the
      time-dependent density functional theory. We surveyed these films by using an 800
      nm Ti:sapphire 120-fs laser with two-photon absorption (TPA) fluorescence
      emission properties and TPA coefficients to obtain the TPA cross sections. A
      three-dimensional optical data storage experiment was conducted by using a TPA
      photoreaction with an 800 nm-fs laser on the film to obtain a seven-layer optical
      data storage. The experiment proves that these carbazole derivatives are well
      suited for two-photon 3D optical storage, thus laying the foundation for the
      research of multilayer high-density and ultra-high-density optical information
      storage materials.

PMID- 25561304
TI  - An efficient and ultrasensitive rhodamine B-based reversible colorimetric
      chemosensor for naked-eye recognition of molybdenum and citrate ions in aqueous
      solution: sensing behavior and logic operation.
AB  - In this paper we manifest a novel rhodamine B (RhB) based colorimetric
      chemosensor for molybdenum and citrate ions (Cit(3-)) in an absolutely aqueous
      media. It has been identified as highly sensitive probe for Mo(6+) which responds
      at 4.0 nmol L(-1) concentration levels. RhB while combined with Mo(6+) in aqueous
      solution displays a color changing from pink to purple which could be quickly
      dissociated by the addition of citrate in this system so that reversible color
      changes from purple to pink can be achieved. The comparison of this method with
      some other methods for citrate indicates that this is the only method which can
      detect citrate in aqueous solution by color changes. This chemosensor can be
      applied for quantification of citrate with a linear range covering from 1.67*10(
      7) to 1.22*10(-5) M and a detection limit of 2.0*10(-8) M. Moreover, the response
      of the chemosensor toward Mo(6+) and citrate is fast. In addition, based on above
      sensing mechanism, an IMPLICATION logic operation can be achieved using Mo(6+)
      ion and Cit(3-) as the inputs, making RhB a promising candidate for further
      applications in molecular logic devices and also indicates that RhB is suitable
      for the detection of Mo(6+) and Cit(3-) ions in real samples.

PMID- 25561305
TI  - Synthesis, luminescence properties and EPR investigation of hydrothermally
      derived uniform ZnO hexagonal rods.
AB  - One-dimensional (1D) zinc oxide (ZnO) hexagonal rods have been successfully
      synthesized by surfactant free hydrothermal process at different temperatures. It
      can be found that the reaction temperature play a crucial role in the formation
      of ZnO uniform hexagonal rods. The possible formation processes of 1-D ZnO
      hexagonal rods were investigated. The zinc hydroxide acts as the morphology
      formative intermediate for the formation of ZnO nanorods. Upon excitation at 325
      nm, the sample prepared at 180 degrees C show several emission bands at 400 nm
      (~3.10 eV), 420 nm (~2.95 eV), 482 nm (~2.57 eV) and 524 nm (~2.36 eV)
      corresponding to different kind of defects. TL studies were carried out by pre
      irradiating samples with gamma-rays ranging from 1 to 7 kGy at room temperature.
      A well resolved glow peak at ~354 degrees C was recorded which can be ascribed to
      deep traps. Furthermore, the defects associated with surface states in ZnO nano
      structures are characterized by electron paramagnetic resonance.

PMID- 25561306
TI  - Health status of HIV-infected women entering care: baseline medical findings from
      the women of color initiative.
AB  - The WOC Initiative is a prospective study of 921 women of color (WOC) entering
      HIV care at nine (three rural, six urban) sites across the US. A baseline
      interview was performed that included self-reported limitation(s) in activity,
      health conditions, and the CDC's health-related quality of life measures (Healthy
      Days). One-third of the WOC reported limiting an activity because of illness or a
      health condition and those with an activity limitation reported 13 physically and
      14 mentally unhealthy days/month, compared with 5 physically and 9 mentally
      unhealthy days/month in the absence of an activity limitation. Age was associated
      with a three- to fourfold increased risk of an activity limitation but only for
      WOC in the urban sites. Diabetes was associated with a threefold increased risk
      of a limitation among women at rural sites. Cardiac disease was associated with a
      six- to sevenfold increased risk of an activity limitation for both urban and
      rural WOC. HIV+ WOC reported more physically and mentally unhealthy days than the
      general US female population even without an activity limitation. Prevention and
      treatment of diabetes and cardiovascular disease will need to be a standard part
      of HIV care to promote the long-term health and HRQOL for HIV-infected WOC.

PMID- 25561307
TI  - Considering care-seeking behaviors reveals important differences among HIV
      positive women not engaged in care: implications for intervention.
AB  - We sought to examine characteristics of HIV-positive women with varying levels of
      engagement in care and care-seeking behaviors. From 2010 to 2013, in a multi-site
      US-based study of engagement in care among HIV-positive women, we conducted
      baseline interviews, which included socio-demographic, clinical, and risk
      behavior characteristics, and barriers to care. We used multinomial logistic
      regression to compare differences among three distinct categories of 748 women:
      engaged in care; not engaged in care, but seeking care ("seekers"); and not
      engaged in care and not seeking care ("non-seekers"). Compared with women in
      care, seekers were more likely to be uninsured and to report fair or poor health
      status. In contrast, non-seekers were not only more likely to be uninsured, but,
      also, to report current high-risk drug use and sexual behaviors, and less likely
      to report transportation as a barrier to care. Examining care-seeking behaviors
      among HIV-positive women not engaged in care revealed important differences in
      high-risk behaviors. Because non-seekers represent a particularly vulnerable
      population of women who are not engaged in care, interventions targeting this
      population likely need to address drug use and be community-based given their
      limited interaction with the health care system.

PMID- 25561308
TI  - Violence screening and viral load suppression among HIV-positive women of color.
AB  - Recent research suggests intimate partner violence (IPV) is commonly experienced
      by many people living with HIV/AIDS, which can complicate their care. We
      introduce a novel approach to screening for history of violence among 102 women
      of color living with HIV and receiving care at an outpatient public health
      clinic. Using a composite measure composed of data from a variety of screening
      tools, we were able to determine that 70.6% of the women had a history of
      violence using the composite measure, and that 43% screened positive using
      multiple screening tools. Although overall viral load suppression rate was high
      at 81.4%, women with a history of violence were less likely to be virally
      suppressed when compared to those without such a history (76.4% versus 93.3%,
      p<0.05). Our findings suggest using a variety of screening questions at entry and
      at follow-up care appointments may be key to identifying and supporting women
      survivors who may not disclose violence when first asked. Future research should
      foster further development, analysis, and use of a variety of screening tools
      such as those used in this study.

PMID- 25561310
TI  - Electric birefringence anomaly of solutions of ionically charged anisometric
      particles.
AB  - The term "electric birefringence anomaly" is known as the electric birefringence
      (EB) signal that occurs in solutions of ionically charged anisometric particles
      in a narrow concentration region. The signal is of opposite sign to the normal
      birefringence that occurs below and above this narrow concentration region. The
      normal electric birefringence signals in the dilute and more concentrated regions
      are due to the orientation of the particles in the direction of the applied
      electric field. The origin for the anomalous signal was not completely understood
      until now. The article summarises previous results in which the anomalous results
      had been observed but not well understood. It shows that the birefringence
      anomaly occurs in systems as diverse as micellar solutions, polyelectrolytes,
      solutions of clays, viruses and fibres. In all these systems the anomaly signals
      are present at the concentration when the length of the colloidal particles
      including the thickness of the electric double layer are about the same as the
      mean distance between the colloidal particles. Under these conditions the
      electric double layers of the particles overlap along the main axis of the
      particles but not in the direction across the particles. As a consequence of this
      situation a dipole is built up across the particles by the migration of the
      counter-ions of the particles in the electric field and this dipole leads to an
      orientation of the particles perpendicular to the electric field. The anomalous
      signal can usually be observed simultaneously with the normal signal. The
      amplitude of the anomalous signal can be larger than the amplitude of the normal
      signal. As a consequence the total birefringence changes its sign in the
      anomalous concentration region. The anomaly signal of the clays can also be
      explained by a fluctuating dipole around the particles, which is due to the fact
      that the centre of the ionic charges of the particles does not fall on the centre
      of the ionic charge of the counter-ions. The resulting dipole could also explain
      the anomaly signal. 

PMID- 25561309
TI  - Simulating patterns of patient engagement, treatment adherence, and viral
      suppression: a system dynamics approach to evaluating HIV care management.
AB  - System dynamics (SD) modeling belongs to the rapidly evolving, interdisciplinary
      field of system science research. This field adds value to more traditional
      health research by contributing to the design and testing of complex integrated
      models of change, to examine health system performance and patient outcomes.
      Using selected milestones in HIV care management to frame our simulation
      research, we created a SD model to examine three patient subgroups of women of
      color (WOC) represented in our multi-site cohort, classified by their health care
      seeking status at baseline. Asked to reflect on their circumstance 6 months prior
      to enrollment in the MSE cohort, 53% noted they were receiving some care (In
      Care, n = 341), 31% that they had been seeking care (Seeking Care, n = 201), and
      16% that they were undecided about seeking care (i.e., answered that they may or
      may not look for care) for treatment of their HIV (May or May Not Seek Care, n =
      103). Our SD model compared simulated patterns of patient retention over 24
      months in relation to: (1) access to antiretroviral therapy (ART), (2) adherence
      to ART, and (3) viral suppression. Assessed patterns yielded insights about
      system capacities and constraints in the context of the SPNS initiative under
      evaluation.

PMID- 25561312
TI  - Intravenous thrombolysis for acute ischemic stroke in a patient receiving
      rivaroxaban.
AB  - BACKGROUND: Rivaroxaban is an oral direct factor Xa inhibitor increasingly used
      in stroke prevention in nonvascular atrial fibrillation, primary prevention and
      treatment of venous thromboembolism, and secondary prevention in acute coronary
      syndromes. METHODS: Thrombolytic treatment has established efficacy in acute
      ischemic stroke. RESULTS: We report the case of a 76-year-old female under
      rivaroxaban for paroxysmal nonvalvular atrial fibrillation who presented an acute
      ischemic stroke. The brain magnetic resonance imaging diffusion-weighted
      sequences showed increased signal in the territory of the left middle cerebral
      artery. Platelet count was normal. PT was 55% (normal, 70-120); the international
      normalized ratio was 1.51 (normal, .90-1.40). She underwent intravenous
      thrombolysis 210 minutes after stroke onset without bleeding complication and
      with complete clinical recovery. CONCLUSIONS: This case underlines the need for
      further studies on the safety of thrombolysis in stroke patients taking
      rivaroxaban. Our case emphasizes the urgent need for sensitive coagulation bed
      side tests during stroke emergencies.

PMID- 25561311
TI  - Chlorogenic acid inhibits hypoxia-induced angiogenesis via down-regulation of the
      HIF-1alpha/AKT pathway.
AB  - BACKGROUND: The hypoxia-inducible factor-1 (HIF-1) is known to play an important
      role in cellular responses to hypoxia, including the transcriptional activation
      of a number of genes involved in tumor angiogenesis. Chlorogenic acid (CGA), one
      of the most abundant polyphenols in the human diet, has been reported to inhibit
      cancer cell growth. The effect of CGA on tumor angiogenesis and its underlying
      mechanisms are, as yet, unknown. METHODS: The effect of CGA on HIF-1alpha
      expression was assessed by Western blot and reverse transcriptase-polymerase
      chain reaction (RT-PCR) assays in A549 lung cancer cells. The transcriptional
      activity of the HIF-1 complex was confirmed using a luciferase assay. To assess
      whether angiogenic factors are increased under hypoxic conditions in these cells,
      vascular endothelial growth factor (VEGF) expression levels were measured by RT
      PCR and Western blotting. The direct effect of CGA on human vascular endothelial
      cells (HUVEC) under hypoxic conditions was analyzed using in vitro assays,
      including tube-formation, wound healing and Transwell invasion assays. To
      investigate the effect of CGA on angiogenesis in vivo, we performed a Matrigel
      plug assay in a mouse model. Finally, the effect of CGA on AKT and ERK activation
      (phosphorylation) as a putative mechanism underlying the effect of CGA on VEGF
      mediated angiogenesis inhibition was assessed using Western blotting. RESULTS: We
      found that CGA significantly decreases the hypoxia-induced HIF-1alpha protein
      level in A549 cells, without changing its mRNA level. CGA was, however, found to
      suppress the transcriptional activity of HIF-1alpha under hypoxic conditions,
      leading to a decrease in the expression of its downstream target VEGF. We also
      found that CGA can block hypoxia-stimulated angiogenesis in vitro and VEGF
      stimulated angiogenesis in vivo using HUVEC cells. In addition, we found that CGA
      can inhibit the HIF-1alpha/AKT signaling pathway, which plays an important role
      in VEGF activation and angiogenesis. CONCLUSIONS: Our data indicate that CGA
      plays a role in the suppression of angiogenesis via inhibition of the HIF
      1alpha/AKT pathway. CGA may represent a novel therapeutic option for the
      treatment of (lung) cancer.

PMID- 25561313
TI  - Rostrocaudal thickness on sagittal diffusion-weighted imaging as a predictor of
      motor deficits in an acute isolated pontine infarction.
AB  - BACKGROUND: The relationship between infarct dimensions and neurologic severity
      in patients with acute pontine infarctions remains unclear. This study aimed to
      clarify the morphometric predictive value of magnetic resonance imaging for motor
      deficits in pontine infarction. METHODS: Nineteen patients with an acute pontine
      infarction (12 males and 7 females, 70.6 +/- 13.5 years [mean age +/- SD]) had
      ventrodorsal length and rostrocaudal thickness and width retrospectively measured
      as parameters of infarct size on axial and sagittal diffusion-weighted imaging
      (DWI). Each patient's functional score (FS) based on Brunnstrom scale (upper
      limb, hand, and lower limb) was assessed. The functional score of bulbar symptoms
      was coded as follows: 2, none; 1, dysarthria or dysphasia; and 0, both. The mean
      FS was compared with each infarct size parameter and the patients' clinical
      features. RESULTS: Rostrocaudal thickness on sagittal DWI was the parameter most
      closely correlated with FS (Spearman rank correlation coefficient (rs) = -.474, P
      = .040). However, there is apparently no association between FS and infarct size
      with correction for age. FS was most severe in patients with an atherothrombotic
      infarction; it was mildest in patients with a lacunar infarction (value of K
      [Kruskal-Wallis] = 9.0, P = .015). CONCLUSIONS: The branch orifices of the
      pontine paramedian arteries could be narrowed by atheromatous plaques within the
      basilar artery. These atheromatous lesions involving multiple branching
      paramedian arteries probably cause rostrocaudally thick infarctions. A pontine
      infarction extending rostrocaudally along the corticospinal tract may cause
      severe motor impairments.

PMID- 25561314
TI  - Noncardiogenic stroke patients with metabolic syndrome have more border-zone
      infarction and intracranial artery stenosis.
AB  - BACKGROUND: Little is known about the clinical character of stroke patients with
      metabolic syndrome (MetS) in Chinese population. In this hospital-based cross
      sectional study, we elucidated the prevalence of MetS among patients with acute
      noncardiogenic cerebral infarction from south China, the topographic infarction
      patterns in magnetic resonance imaging, and vascular angiography findings of
      stroke patients with MetS. METHODS: The patients with acute noncardiogenic stroke
      were clinically evaluated including waistline circumference, blood pressure,
      glycemia, serum triglyceride, high-density lipoprotein cholesterol level,
      magnetic resonance imaging, and angiography evaluation, including magnetic
      resonance angiography, computed tomography angiography, or digital subtraction
      angiography for intracranial (IC) and extracranial arteries. According to the
      National Cholesterol Education Program Adult Treatment Panel III criterion, the
      patients were classified into the MetS and non-MetS groups. RESULTS: Among 222
      patients studied, the prevalence of MetS was 54.5%, and there were more women in
      the MetS group than in the non-MetS group (P < .05). Frequency of all the
      individual factors of MetS was higher in the MetS group than in the non-MetS
      group (P < .05). The lesion pattern of border-zone (BZ) infarction was more
      prevalent in MetS patients (P < .05). The frequency of IC artery stenosis was
      higher in the MetS group than in the non-MetS group (odds ratio [OR], 1.8; 95%
      confidence interval [CI], 1.0-3.0). After adjustment for age and gender, IC
      stenosis was significantly associated with large waistline circumference (OR,
      .95; 95% CI, .91-.99). CONCLUSIONS: According to our findings, MetS was of high
      prevalence in noncardiogenic stroke patients in China, and female patients were
      more likely to have MetS. The MetS patients tended to have more BZ infarctions
      and more IC artery stenosis than the non-MetS stroke patients.

PMID- 25561315
TI  - Multiple myxomatous aneurysms with bypass and clipping in a 37-year-old man.
AB  - BACKGROUND: Cardiac myxoma is the most common cardiac tumor. Neurologic
      complications are seen in 20%-35%, most frequently embolic ischemic stroke, and
      rarely secondary to intracranial aneurysms. The mechanism of aneurysm formation
      in these patients is speculative. METHODS: We report, herein, a 37-year-old male
      with a cardiac myxoma who experienced repeated ischemic stroke and intracerebral
      hematoma despite resection of heart tumor, secondary to multiple cerebral
      aneurysm. RESULTS: We offered him surgery with a bypass and clipping, because
      growing of aneurysm was not suitable for endovascular treatment. CONCLUSION:
      Bypass and clipping are possible options in this type of disease. Aneurysm biopsy
      supports mycotic theory of aneurysm formation.

PMID- 25561317
TI  - Comparison of cerebral blood flow data obtained by computed tomography (CT)
      perfusion with that obtained by xenon CT using 320-row CT.
AB  - Cerebral blood flow (CBF) data obtained by computed tomography perfusion (CTP)
      imaging have been shown to be qualitative data rather than quantitative, in
      contrast with data obtained by other imaging methods, such as xenon CT (XeCT)
      imaging. Thus, interpatient comparisons of CBF values themselves obtained by CTP
      may be inaccurate. In this study, we have compared CBF ratios as well as CBF
      values obtained from CTP-CBF data to those obtained from XeCT-CBF data for the
      same patients to determine CTP-CBF parameters that can be used for interpatient
      comparisons. The data used in the present study were obtained as volume data
      using 320-row CT. The volume data were applied to an automated region of interest
      determining software (3DSRT, version 3.5.2 ) and converted to 59 slices of 2 mm
      interval standardized images. In the present study, we reviewed 10 patients with
      occlusive cerebrovascular diseases (CVDs) undergoing both CTP and XeCT in the
      same period. Our study shows that ratios of CBF measurements, such as hemodynamic
      stress distribution (perforator-to-cortical flow ratio of middle cerebral artery
      [MCA] region) or the left/right ratio for the region of the MCA, calculated using
      CTP data have been shown to correlate well with the same ratios calculated using
      XeCT data. These results suggest that such CBF ratios could be useful for
      generating interpatient comparisons of CTP-CBF data obtained by 320-row CT among
      patients with occlusive CVD.

PMID- 25561316
TI  - Neuroprotective activity of creatylglycine ethyl ester fumarate.
AB  - BACKGROUND: We have recently shown neuroprotective activity of the creatine
      amides in the focal cerebral ischemia in rats on the 280 mg/kg administration. In
      the present study, neuroprotective properties of creatylglycine ethyl ester
      fumarate (CrGEt) in rats with focal cerebral ischemia were explored in a wide
      dosage range (30-280 mg/kg, intravenous and intragastric). METHODS: Focal
      cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO).
      RESULTS: The CrGEt administration 30 minutes before and at the last 5 minutes of
      MCAO dose dependently attenuated cerebral ischemic damage on 35%-65%, reduced
      neurobehavioral deficits, led to high neuronal survival in ischemic rat brains.
      The neuroprotective activity of CrGEt was mediated by its following abilities:
      (1) normalize the energy metabolism in the ischemic brains, maintaining adenosine
      triphosphate levels, and reducing lactate concentration; (2) inhibit the ischemia
      reperfusion-related oxidative stress as evidenced by the increased activity of
      superoxide dismutase and the reduced levels of malondialdehyde. CrGEt served as a
      substrate for creatine kinase and a partial agonist of N-methyl-D-aspartate
      receptors; this partly explains mechanism of its neuroprotective action.
      CONCLUSIONS: In view of the previously mentioned results, CrGEt holds a promise
      as a compound for treatment of ischemic brain disorders.

PMID- 25561319
TI  - Engineering the robustness of Saccharomyces cerevisiae by introducing
      bifunctional glutathione synthase gene.
AB  - Robust, high-yielding Saccharomyces cerevisiae is highly desirable for cost
      effective cellulosic ethanol production. In this study, the bifunctional
      glutathione (GSH) synthetase genes GCSGS at high copy number was integrated into
      ribosomal DNA of S. cerevisiae by Cre-LoxP system. Threefold higher GSH contents
      (54.9 MUmol/g dry weight) accumulated in the engineered strain BY-G compared to
      the reference strain. Tolerance of BY-G to H2O2 (3 mM), temperature (40  degrees
      C), furfural (10 mM), hydroxymethylfurfural (HMF, 10 mM) and 0.5 mM Cd(2+)
      increased compared to reference strain. Twofold higher ethanol concentration was
      obtained by BY-G in simultaneous saccharification and fermentation of corn stover
      compared to the reference strain. The results showed that intracellular GSH
      content of S. cerevisiae has an influence on robustness. The strategy is used to
      engineer S. cerevisiae strains adaptive to a combination of tolerance to
      inhibitors and raised temperature that may occur in high solid simultaneous
      saccharification and fermentation of lignocellulosic feedstocks. 

PMID- 25561320
TI  - Interleukin-23 receptor single nucleotide polymorphisms in Crohn's disease.

PMID- 25561318
TI  - Engineering the supply chain for protein production/secretion in yeasts and
      mammalian cells.
AB  - Metabolic bottlenecks play an increasing role in yeasts and mammalian cells
      applied for high-performance production of proteins, particularly of
      pharmaceutical ones that require complex posttranslational modifications. We
      review the present status and developments focusing on the rational metabolic
      engineering of such cells to optimize the supply chain for building blocks and
      energy. Methods comprise selection of beneficial genetic modifications, rational
      design of media and feeding strategies. Design of better producer cells based on
      whole genome-wide metabolic network analysis becomes increasingly possible. High
      resolution methods of metabolic flux analysis for the complex networks in these
      compartmented cells are increasingly available. We discuss phenomena that are
      common to both types of organisms but also those that are different with respect
      to the supply chain for the production and secretion of pharmaceutical proteins.

PMID- 25561322
TI  - A new hypothesis of sex-differences in temporomandibular disorders: estrogen
      enhances hyperalgesia of inflamed TMJ through modulating voltage-gated sodium
      channel 1.7 in trigeminal ganglion?
AB  - OBJECTIVE: Temporomandibular disorders (TMD) are an assorted set of clinical
      conditions characterized mainly by pain in the temporomandibular joint (TMJ). TMJ
      inflammation or synovitis is frequently observed in TMD patients and is the major
      reason for TMD pain. TMD is prevalent in women of childbearing age, at least
      twice than in men, implying that estrogen may be involved in TMD pain processing.
      Estrogen affects a cell mainly through the estrogen receptors (ER). The estrogen
      ER complex binds to estrogen response element sequences (ERE) in the promoter
      region of specific genes and then exerts its regulatory potential. The voltage
      gated sodium channel 1.7 (Nav1.7), whose single disruption leads to a complete
      loss of pain, amplifies weak stimuli in the neurons and acts as the threshold
      channel for firing action potentials and plays a prominent role in pain
      perception, including inflammatory pain. Furthermore, our previous study showed
      that trigeminal ganglionic Nav1.7 was involved in the hyperalgesia of the
      inflamed TMJ. We propose that estrogen may enhance hyperalgesia of inflamed TMJ
      through decrease nociceptive threshold of TMJ or inflamed TMJ by modulating both
      expression and channel threshold of Nav1.7 in trigeminal ganglion.

PMID- 25561321
TI  - Optimal inference with suboptimal models: addiction and active Bayesian
      inference.
AB  - When casting behaviour as active (Bayesian) inference, optimal inference is
      defined with respect to an agent's beliefs - based on its generative model of the
      world. This contrasts with normative accounts of choice behaviour, in which
      optimal actions are considered in relation to the true structure of the
      environment - as opposed to the agent's beliefs about worldly states (or the
      task). This distinction shifts an understanding of suboptimal or pathological
      behaviour away from aberrant inference as such, to understanding the prior
      beliefs of a subject that cause them to behave less 'optimally' than our prior
      beliefs suggest they should behave. Put simply, suboptimal or pathological
      behaviour does not speak against understanding behaviour in terms of (Bayes
      optimal) inference, but rather calls for a more refined understanding of the
      subject's generative model upon which their (optimal) Bayesian inference is
      based. Here, we discuss this fundamental distinction and its implications for
      understanding optimality, bounded rationality and pathological (choice)
      behaviour. We illustrate our argument using addictive choice behaviour in a
      recently described 'limited offer' task. Our simulations of pathological choices
      and addictive behaviour also generate some clear hypotheses, which we hope to
      pursue in ongoing empirical work. 

PMID- 25561323
TI  - A landmark report on improving medicines for children.

PMID- 25561324
TI  - Immunosuppressive Medication Adherence, Therapeutic Adherence, School
      Performance, Symptom Experience, and Depression Levels in Patients Having
      Undergone a Liver Transplant During Childhood.
AB  - OBJECTIVES: This study sought to investigate immunosuppressive medication
      adherence, therapeutic adherence, school performance, symptom experiences, and
      depression levels of patients having undergone liver transplant during childhood.
      MATERIALS AND METHODS: We performed a retrospective, cross-sectional, case
      controlled study to compare the depression levels of subjects with those of their
      healthy peers. Data were collected between June 23, 2014, and July 10, 2014, from
      0- to 18-year-old patients having undergone a liver transplant between 1996 and
      2014 (n = 27; the participant's mean age, 17.59 y [SD = 4.29, min-max = 8-28 y]).
      The mean score for the immunosuppressant therapy adherence was 11.18. To collect
      the data, the Demographic and Clinical Characteristics Form, Immunosuppressant
      Therapy Adherence Scale, Therapeutic Regimen Adherence Assessment Questionnaire,
      School Performance Assessment Questionnaire, Modified Transplant Symptom
      Occurrence and Symptom Distress Scale-58, and Beck Depression Inventory were
      used. To analyze the data, descriptive statistics (frequencies, mean, and
      standard deviation), Mann-Whitney U test, and ridit scoring were used. RESULTS:
      While the rate of adherence with clinical appointments was 55.5%, it was 33.3%
      with the diet (prescribed regimen) and 44.4% with exercise. While 33.3% of the
      participants repeated a grade or were held back, 44.4% of them missed more than
      20 school days. Of the symptoms, the recipients mostly experienced anxiety,
      restlessness, nervousness, fatigue, and difficulty in concentrating. The
      patients' mean depression score was 7.77 when they were compared to their healthy
      peers, the difference was not statistically significant (P > .05). CONCLUSIONS:
      In our study, the recipients' adherence with immunosuppressive therapy and
      clinical appointment was high. This study will provide data for the literature
      about pediatric liver transplant recipients' adherence with diet and exercise,
      and physiological and psychological symptoms such as fatigue and anxiety.

PMID- 25561325
TI  - Small molecule-sensing strategy and techniques for understanding the
      functionality of green tea.
AB  - Various low-molecular-weight phytochemicals in green tea (Camellia sinensis L.),
      especially (-)-epigallocatechin-3-O-gallate (EGCG), are known to be involved in
      health promotion and disease risk reduction. However, the underlying mechanism
      has remained elusive because of the absence of an analytical technique that can
      easily detect the precise behavior of such a small molecule. Recently, we have
      identified a cell-surface EGCG-sensing receptor and the related signaling
      molecules that control the physiological functions of EGCG. We also developed a
      novel in situ label-free imaging technique for visualizing spatially resolved
      biotransformations based on simultaneous mapping of EGCG and its phase II
      metabolites. Furthermore, we established a chemometric method capable of
      evaluating the functionality of multicomponent green tea extracts by focusing on
      their compositional balances. This review highlights our proposed small molecule
      sensing techniques for detecting the complex behavior of green tea components and
      linking such information to an enhanced understanding of green tea functionality.

PMID- 25561326
TI  - Selection of suitably non-repressing carbon sources for expression of alcohol
      oxidase isozyme promoters in the methylotrophic yeast Pichia methanolica.
AB  - In this work, we aimed to select suitable non-repressing carbon sources for the
      expression of promoters derived from the alcohol oxidase (AOD) isozyme genes,
      PMOD1 and PMOD2, during the growth of Pichia methanolica. Our results revealed
      that xylose is the best non-repressing carbon source for heterologous gene
      expression using both PMOD1 and PMOD2, and that glycerol is also a suitable
      carbon source with by which the on/off of PMOD2 expression can be controlled. 

PMID- 25561327
TI  - Preparation of keratin and chemically modified keratin hydrogels and their
      evaluation as cell substrate with drug releasing ability.
AB  - Keratin was extracted as a reduced form from wool, which was then subjected to
      acetamidation, carboxymethylation or aminoethylation at abundant free cysteine
      residues to give acetamidated keratin (AAK), carboxymethylated keratin (CMK) and
      aminoethylated keratin (AEK). Hydrogels were prepared from intact and three
      chemically modified keratins simply by concentrating their aqueous solution and
      subsequent cooling. The lowest concentration to form a hydrogel without fluidity
      was 110 mg/ml for AAK, 120 mg/ml for AEK, 130 mg/ml for keratin and 180 mg/ml for
      CMK. Comparing with a hydrogel just prepared (swelling ratio: 600-700), each
      hydrogel slightly shrank in an acidic solution. While AAK hydrogel little swelled
      in neutral and basic solutions, other hydrogels became swollen and CMK hydrogel
      reached to dissolution. Hydrogels of keratin, AAK and AEK were found to support
      cell proliferation, although cell elongation on AAK and AEK hydrogel was a little
      suppressed. On the other hand, CMK hydrogel did not seem to be suitable for a
      cell substrate because of its high swelling in culture medium. Evaluation of the
      hydrogels as a drug carrier showed that keratin and AAK hydrogels were good
      sustained drug release carriers, which showed the drug release for more than
      three days, while the release from AEK and CMK hydrogels completed within one
      day. Thus, keratin and chemically modified keratin hydrogels, especially keratin
      and AAK hydrogels, were promising biomaterials as a cell substrate and a
      sustained drug release carrier.

PMID- 25561328
TI  - Microbial degradation of linear peptides by strain B-9 of Sphingosinicella and
      its application in peptide quantification using liquid chromatography-mass
      spectrometry.
AB  - The bacterial strain Sphingosinicella sp. B-9 was originally discovered to have
      the ability to degrade cyanobacterial cyclic peptides (microcystins), and has
      three hydrolytic enzymes (MlrA, MlrB, and MlrC). The purpose of this study was to
      examine in detail the degradation of glucagon/vasoactive intestinal polypeptide
      (VIP) family peptides by B-9, and to investigate the substrate specificity of B-9
      proteases and the possibility of using a B-9 protease as a novel protease for
      peptide quantification by using a surrogate peptide and mass spectrometry (MS).
      The effective use of inhibitors revealed the following hydrolytic capability of B
      9: One of the B-9 proteases (presumably MlrB) that was not inhibited by
      ethylenediaminetetraacetic acid (EDTA) cleaved bioactive peptides into medium
      sized peptides with broad selectivity, similar to neutral endopeptidase, and
      another protease that was not inhibited by phenylmethylsulfonyl fluoride (PMSF)
      corresponded to MlrC and cleaved the resulting medium-sized peptides to smaller
      peptides or amino acids. The former property was desirable to obtain a suitable
      surrogate peptide, which was used successfully to quantify peptide using liquid
      chromatography (LC)-MS. Thus, the present study verified that one of the B-9
      proteases has broad cleavage selectivity and cleavage sites, not seen in
      commercially available proteases, and is applicable to protein and peptide
      quantification using LC-MS. 

PMID- 25561329
TI  - Lactic acid production from biomass-derived sugars via co-fermentation of
      Lactobacillus brevis and Lactobacillus plantarum.
AB  - Lignocellulosic biomass is an attractive alternative resource for producing
      chemicals and fuels. Xylose is the dominating sugar after hydrolysis of
      hemicellulose in the biomass, but most microorganisms either cannot ferment
      xylose or have a hierarchical sugar utilization pattern in which glucose is
      consumed first. To overcome this barrier, Lactobacillus brevis ATCC 367 was
      selected to produce lactic acid. This strain possesses a relaxed carbon
      catabolite repression mechanism that can use glucose and xylose simultaneously;
      however, lactic acid yield was only 0.52 g g(-1) from a mixture of glucose and
      xylose, and 5.1 g L(-1) of acetic acid and 8.3 g L(-1) of ethanol were also
      formed during production of lactic acid. The yield was significantly increased
      and ethanol production was significantly reduced if L. brevis was co-cultivated
      with Lactobacillus plantarum ATCC 21028. L. plantarum outcompeted L. brevis in
      glucose consumption, meaning that L. brevis was focused on converting xylose to
      lactic acid and the by-product, ethanol, was reduced due to less NADH generated
      in the fermentation system. Sequential co-fermentation of L. brevis and L.
      plantarum increased lactic acid yield to 0.80 g g(-1) from poplar hydrolyzate and
      increased yield to 0.78 g lactic acid per g of biomass from alkali-treated corn
      stover with minimum by-product formation. Efficient utilization of both cellulose
      and hemicellulose components of the biomass will improve overall lactic acid
      production and enable an economical process to produce biodegradable plastics. 

PMID- 25561330
TI  - Large-amplitude undulatory swimming near a wall.
AB  - The propulsive dynamics of a flexible undulating foil in a self-propelled
      swimming configuration near a wall is studied experimentally. Measurements of the
      swimming speed and the propulsive force are presented, together with image
      acquisition of the kinematics of the foil and particle image velocimetry (PIV) in
      its wake. The presence of the wall enhances the cruising velocity in some cases
      up to 25% and the thrust by a 45% , for swept angles of 160 and 240 degrees . The
      physical mechanisms underlying this effect are discussed by studying the
      vorticity dynamics in the wake of the foil. Proper orthogonal decomposition is
      applied to the PIV measurements in order to analyse the kinetic energy modal
      distribution in the flow and to relate it to the propulsion generated by the
      foil. 

PMID- 25561332
TI  - gamma Secretase inhibitor BMS-708163 reverses resistance to EGFR inhibitor via
      the PI3K/Akt pathway in lung cancer.
AB  - Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR)
      mutations are sensitive to EGFR tyrosine kinase inhibitor (TKI). Acquired
      resistance to EGFR TKI develops after prolonged treatment. The aim of this study
      was to investigate the effect of the novel gamma secretase inhibitor BMS-708163
      on acquired resistance to the EGFR TKI gefitinib. We did not observe known
      mechanisms of acquired resistance to EGFR TKI, including the EGFR T790M mutation
      and MET gene amplification in the gefitinib-resistant PC9/AB2 cells. BMS-708163
      inhibited PI3K/Akt expression and sensitized PC9/AB2 cells to gefitinib-induced
      cytotoxicity. In contrast, BMS-708163 had no significant effect on gefitinib
      sensitivity in PC9 parental cells. Combined treatment with BMS-708163 and
      gefitinib induced high levels of apoptosis. Our in vivo studies showed that
      combined treatment of gefitinib and BMS-708163 inhibited the growth of PC9/AB2
      xenografts. In conclusion, our data show that combined treatment of gefitinib and
      gamma secretase inhibitors may be useful for treating lung adenocarcinomas
      harboring EGFR mutations with acquired gefitinib resistance.

PMID- 25561333
TI  - Neural representation of probabilities for Bayesian inference.
AB  - Bayesian models are often successful in describing perception and behavior, but
      the neural representation of probabilities remains in question. There are several
      distinct proposals for the neural representation of probabilities, but they have
      not been directly compared in an example system. Here we consider three models: a
      non-uniform population code where the stimulus-driven activity and distribution
      of preferred stimuli in the population represent a likelihood function and a
      prior, respectively; the sampling hypothesis which proposes that the stimulus
      driven activity over time represents a posterior probability and that the
      spontaneous activity represents a prior; and the class of models which propose
      that a population of neurons represents a posterior probability in a distributed
      code. It has been shown that the non-uniform population code model matches the
      representation of auditory space generated in the owl's external nucleus of the
      inferior colliculus (ICx). However, the alternative models have not been tested,
      nor have the three models been directly compared in any system. Here we tested
      the three models in the owl's ICx. We found that spontaneous firing rate and the
      average stimulus-driven response of these neurons were not consistent with
      predictions of the sampling hypothesis. We also found that neural activity in ICx
      under varying levels of sensory noise did not reflect a posterior probability. On
      the other hand, the responses of ICx neurons were consistent with the non-uniform
      population code model. We further show that Bayesian inference can be implemented
      in the non-uniform population code model using one spike per neuron when the
      population is large and is thus able to support the rapid inference that is
      necessary for sound localization. 

PMID- 25561334
TI  - Molecular mechanisms of sulbactam antibacterial activity and resistance
      determinants in Acinetobacter baumannii.
AB  - Sulbactam is a class A beta-lactamase inhibitor with intrinsic whole-cell
      activity against certain bacterial species, including Acinetobacter baumannii.
      The clinical use of sulbactam for A. baumannii infections is of interest due to
      increasing multidrug resistance in this pathogen. However, the molecular drivers
      of its antibacterial activity and resistance determinants have yet to be
      precisely defined. Here we show that the antibacterial activities of sulbactam
      vary widely across contemporary A. baumannii clinical isolates and are mediated
      through inhibition of the penicillin-binding proteins (PBPs) PBP1 and PBP3, with
      very low frequency of resistance; the rare pbp3 mutants with high levels of
      resistance to sulbactam are attenuated in fitness. These results support further
      investigation of the potential clinical utility of sulbactam. 

PMID- 25561335
TI  - Telavancin in vitro activity against a collection of methicillin-resistant
      Staphylococcus aureus isolates, including resistant subsets, from the United
      States.
AB  - Telavancin had MIC50, MIC90, and MIC100 values of 0.03, 0.06, and 0.12 MUg/ml,
      respectively, against methicillin-susceptible Staphylococcus aureus, methicillin
      resistant S. aureus (MRSA), and non-multidrug-resistant (non-MDR) and MDR
      subsets. MRSA with elevated MIC values for vancomycin (2 to 4 MUg/ml) or
      daptomycin (1 to 2 MUg/ml) had telavancin MIC50 (0.06 MUg/ml) values 2-fold
      higher than those of isolates with lower MIC results (MIC50, 0.03 MUg/ml).
      However, telavancin had MIC90 and MIC100 results of 0.06 and 0.12 MUg/ml (100%
      susceptible), respectively, regardless of the MRSA subset. 

PMID- 25561336
TI  - In vitro prediction of the evolution of GES-1 beta-lactamase hydrolytic activity.
AB  - Resistance to beta-lactams is constantly increasing due to the emergence of
      totally new enzymes but also to the evolution of preexisting beta-lactamases. GES
      1 is a clinically relevant extended-spectrum beta-lactamase (ESBL) that
      hydrolyzes penicillins and broad-spectrum cephalosporins but spares monobactams
      and carbapenems. However, several GES-1 variants (i.e., GES-2 and GES-5)
      previously identified among clinical isolates display an extended spectrum of
      activity toward carbapenems. To study the evolution potential of the GES-1 beta
      lactamase, this enzyme was submitted to in vitro-directed evolution, with
      selection on increasing concentrations of the cephalosporin cefotaxime, the
      monobactam aztreonam, or the carbapenem imipenem. The highest resistance levels
      were conferred by a combination of up to four substitutions. The A6T-E104K-G243A
      variant selected on cefotaxime and the A6T-E104K-T237A-G243A variant selected on
      aztreonam conferred high resistance to cefotaxime, ceftazidime, and aztreonam.
      Conversely, the A6T-G170S variant selected on imipenem conferred high resistance
      to imipenem and cefoxitin. Of note, the A6T substitution involved in higher MICs
      for all beta-lactams is located in the leader peptide of the GES enzyme and
      therefore is not present in the mature protein. Acquired cross-resistance was not
      observed, since selection with cefotaxime or aztreonam did not select for
      resistance to imipenem, and vice versa. Here, we demonstrate that the beta
      lactamase GES-1 exhibits peculiar properties, with a significant potential to
      gain activity against broad-spectrum cephalosporins, monobactams, and
      carbapenems. 

PMID- 25561337
TI  - A phase 2, randomized, double-blind, multicenter trial to evaluate the safety and
      efficacy of three dosing regimens of isavuconazole compared with fluconazole in
      patients with uncomplicated esophageal candidiasis.
AB  - Esophageal candidiasis is a frequent cause of morbidity in immunocompromised
      patients. Isavuconazole is a novel, broad-spectrum antifungal developed for the
      treatment of opportunistic fungal infections. This phase 2 trial compared the
      efficacy and safety of three oral dosing regimens of isavuconazole with an oral
      fluconazole regimen in the primary treatment of uncomplicated esophageal
      candidiasis. The isavuconazole regimens were as follows: 200 mg on day 1 and then
      50 mg once daily (arm A), 400 mg on day 1 and then 400 mg once-weekly (arm B),
      and 400 mg on day 1 and then 100 mg once daily (arm C). Patients in arm D
      received fluconazole at 200 mg on day 1 and then 100 mg once daily. The minimum
      treatment duration was 14 days. The primary endpoint was the rate of
      endoscopically confirmed clinical response at end of therapy. Safety and
      tolerability were also assessed. Efficacy was evaluated in 153 of 160 enrolled
      patients. Overall, 146 (95.4%) achieved endoscopically confirmed clinical
      success. Each of the isavuconazole regimens was shown to be not inferior to
      fluconazole, i.e., arm A versus D, -0.5% (95% confidence interval [CI] -10.0 to
      9.4), arm B versus D, 3.5% (95% CI, -5.6 to 12.7), and arm C versus D, -0.2% (95%
      CI, -9.8 to 9.4). The frequency of adverse events was similar in arm A (n = 22;
      55%), arm B (n = 18; 45%), and arm D (n = 22; 58%), but higher in arm C (n = 29;
      71%). In summary, efficacy and safety of once-daily and once-weekly isavuconazole
      were comparable with once-daily fluconazole in the primary treatment of
      uncomplicated esophageal candidiasis. 

PMID- 25561338
TI  - Extended-duration dosing and distribution of dalbavancin into bone and articular
      tissue.
AB  - Dalbavancin is an intravenous lipoglycopeptide with activity against Gram
      positive pathogens and an MIC90 for Staphylococcus aureus of 0.06 MUg/ml. With a
      terminal half-life of >14 days, dosing regimens with infrequent parenteral
      administration become available to treat infectious diseases such as
      osteomyelitis and endocarditis that otherwise require daily dosing for many
      weeks. In order to support a rationale for these novel regimens, the
      pharmacokinetics over an extended dosing interval and the distribution of
      dalbavancin into bone and articular tissue were studied in two phase I trials and
      pharmacokinetic modeling was performed. Intravenous administration of 1,000 mg of
      dalbavancin on day 1 followed by 500 mg weekly for seven additional weeks was
      well tolerated and did not demonstrate evidence of drug accumulation. In a
      separate study, dalbavancin concentrations in cortical bone 12 h after infusion
      of a single 1,000-mg intravenous infusion were 6.3 MUg/g and 2 weeks later were
      4.1 MUg/g. A two-dose, once-weekly regimen that would provide tissue exposure
      over the dalbavancin MIC for Staphylococcus aureus for 8 weeks, maximizing the
      initial exposure to treatment while minimizing the frequency of intravenous
      therapy, is proposed. 

PMID- 25561340
TI  - From the viral perspective: infectious salmon anemia virus (ISAV) transcriptome
      during the infective process in Atlantic salmon (Salmo salar).
AB  - The infectious salmon anemia virus (ISAV) is a severe disease that mainly affects
      the Atlantic salmon (Salmo salar) aquaculture industry. Although several
      transcriptional studies have aimed to understand Salmon-ISAV interaction through
      the evaluation of host-gene transcription, none of them has focused their
      attention upon the viral transcriptional dynamics. For this purpose, RNA-Seq and
      RT-qPCR analyses were conducted in gills, liver and head-kidney of S. salar
      challenged by cohabitation with ISAV. Results evidence the time and tissue
      transcript patterns involved in the viral expression and how the transcription
      levels of ISAV segments are directly linked with the protein abundance found in
      other virus of the Orthomyxoviridae family. In addition, RT-qPCR result evidenced
      that quantification of ISAV through amplification of segment 3 would result in a
      more sensitive approach for detection and quantification of ISAV. This study
      offers a more comprehensive approach regarding the ISAV infective process and
      gives novel knowledge for its molecular detection. 

PMID- 25561339
TI  - Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae at a single
      institution: insights into endemicity from whole-genome sequencing.
AB  - The global emergence of Klebsiella pneumoniae carbapenemase-producing K.
      pneumoniae (KPC-Kp) multilocus sequence type ST258 is widely recognized. Less is
      known about the molecular and epidemiological details of non-ST258 K. pneumoniae
      in the setting of an outbreak mediated by an endemic plasmid. We describe the
      interplay of blaKPC plasmids and K. pneumoniae strains and their relationship to
      the location of acquisition in a U.S. health care institution. Whole-genome
      sequencing (WGS) analysis was applied to KPC-Kp clinical isolates collected from
      a single institution over 5 years following the introduction of blaKPC in August
      2007, as well as two plasmid transformants. KPC-Kp from 37 patients yielded 16
      distinct sequence types (STs). Two novel conjugative blaKPC plasmids (pKPC_UVA01
      and pKPC_UVA02), carried by the hospital index case, accounted for the presence
      of blaKPC in 21/37 (57%) subsequent cases. Thirteen (35%) isolates represented an
      emergent lineage, ST941, which contained pKPC_UVA01 in 5/13 (38%) and pKPC_UVA02
      in 6/13 (46%) cases. Seven (19%) isolates were the epidemic KPC-Kp strain, ST258,
      mostly imported from elsewhere and not carrying pKPC_UVA01 or pKPC_UVA02. Using
      WGS-based analysis of clinical isolates and plasmid transformants, we demonstrate
      the unexpected dispersal of blaKPC to many non-ST258 lineages in a hospital
      through spread of at least two novel blaKPC plasmids. In contrast, ST258 KPC-Kp
      was imported into the institution on numerous occasions, with other blaKPC
      plasmid vectors and without sustained transmission. Instead, a newly recognized
      KPC-Kp strain, ST941, became associated with both novel blaKPC plasmids and
      spread locally, making it a future candidate for clinical persistence and
      dissemination. 

PMID- 25561341
TI  - The metallobiochemistry of ultratrace levels of platinum group elements in the
      rat.
AB  - The use of platinum, palladium and rhodium (Platinum Group Elements - PGEs) and
      the possibility of exposure to their ultratrace levels is increasing. In fact,
      the exponential development of metallic PGE-based nanoparticles (<100 nm in size)
      opens extraordinary perspectives in the areas of electrocatalysts and catalytic
      converters, magnetic nanopowders, polymer membranes, cancer therapy, coatings,
      plastics, nanofibres and textiles. Like other metal-based nanoparticles, exposure
      to PGEs nanoparticles may result in a release of ultratrace amounts of Pt, Pd, Rh
      ions in the body whose metabolic fate and toxicity still need to be evaluated.
      Furthermore, PGEs can act as allergic sensitizers by acting as haptens and
      inducing both type I and IV allergic reactions. In this work we studied the in
      vivo metabolic patterns of ultratrace levels of potent allergens and sensitizers
      PGE halogenated salts. (191)Pt, (103)Pd and (101m)Rh radioisotopes were prepared
      via cyclotron irradiation and used for radiolabelling Na2(191)PtCl4,
      Na2(103)PdCl4 and Na2(101m)RhCl6 salts. These anionic chlorocomplexes were
      intraperitoneally injected into rats (114 ng Pt kg(-1) bodyweight; 24 ng Pd kg(
      1) b.w.; 16 ng Rh kg(-1) b.w.). At 16 h post-exposure, PGEs were poorly but
      significantly retained in all tissues analysed. Kidneys, spleen, adrenal gland,
      liver, pancreas and small intestine were the organs with the highest Pt, Pd, Rh
      concentrations. In the blood 30-35% of (103)Pd and (191)Pt and 10% of (101m)Rh
      were recovered in the plasma, mainly bound to albumin and to a less extent to
      transferrin. The hepatic and renal intracellular distribution showed the highest
      recovery of (191)Pt, (103)Pd and (101m)Rh in the nuclear fraction (liver) and in
      the cytosol (kidney). Chromatographic separation and ultrafiltration experiments
      on kidney and liver cytosols showed the strong ability of biochemical
      macromolecules to bind (191)Pt, (103)Pd and (101m)Rh, and being responsible for
      the retention of the three elements in the body. The link to macromolecules is
      the basis for the sensitizing capacity of PGEs. 

PMID- 25561343
TI  - The involvement of gut microbiota in inflammatory bowel disease pathogenesis:
      potential for therapy.
AB  - Over the past recent years, a great number of studies have been directed toward
      the evaluation of the human host-gut microbiota interaction, with the goal to
      progress the understanding of the etiology of several complex diseases.
      Alterations in the intestinal microbiota associated with inflammatory bowel
      disease are well supported by literature data and have been widely accepted by
      the research community. The concomitant implementation of high-throughput
      sequencing techniques to analyze and characterize the composition of the
      intestinal microbiota has reinforced the view that inflammatory bowel disease
      results from altered interactions between gut microbes and the mucosal immune
      system and has raised the possibility that some form of modulation of the
      intestinal microbiota may constitute a potential therapeutic basis for the
      disease. The aim of this review is to describe the changes of gut microbiota in
      inflammatory bowel disease, focusing the attention on its involvement in the
      pathogenesis of the disease, and to review and discuss the therapeutic potential
      to modify the intestinal microbial population with antibiotics, probiotics,
      prebiotics, synbiotics and fecal microbiota transplantation. 

PMID- 25561342
TI  - Diagnosis and incidence risk of clinical canine monocytic ehrlichiosis under
      field conditions in Southern Europe.
AB  - BACKGROUND: Canine Monocytic Ehrlichiosis (CME), due to the bacterium Ehrlichia
      canis and transmitted by the brown dog tick Rhipicephalus sanguineus, is a major
      tick-borne disease in southern Europe. In this area, infections with other vector
      borne pathogens (VBP) are also described and result in similar clinical
      expression. The aim of the present study was to evaluate the incidence risk of
      clinical CME in those endemic areas and to assess the potential involvement of
      other VBP in the occurrence of clinical and/or biological signs evocative of the
      disease. METHODS: The study was conducted from April to November 2011 in
      veterinary clinics across Italy, Spain and Portugal. Sick animals were included
      when fitting at least three clinical and/or biological criteria compatible with
      ehrlichiosis. Serological tests (SNAP(r)4Dx, SNAP(r)Leish tests, Idexx, USA) and
      diagnostic PCR for E. canis, Anaplasma platys, Anaplasma phagocytophilum, Babesia
      spp, Hepatozoon canis and Leishmania infantum detection were performed to
      identify the etiological agents. Ehrlichiosis was considered when three clinical
      and/or biological suggestive signs were associated with at least one positive
      paraclinical test (serology or PCR). The annual incidence risk was calculated and
      data were geo-referenced for map construction. The probabilities of CME and other
      vector-borne diseases when facing clinical and/or biological signs suggestive of
      CME were then evaluated. RESULTS: A total of 366 dogs from 78 veterinary clinics
      were enrolled in the survey. Among them, 99 (27%) were confirmed CME cases, which
      allowed an estimation of the average annual incidence risk of CME amongst the
      investigated dog population to be 0.08%. Maps showed an increasing gradient of
      CME incidence risk from northern towards southern areas, in particular in Italy.
      It also suggested the existence of hot-spots of infections by VBP in Portugal. In
      addition, the detection of other VBP in the samples was common and the study
      demonstrated that a dog with clinical signs evocative of CME is as likely to be
      positive to Ehrlichia canis as to another VBP. CONCLUSIONS: The study confirms
      the endemicity of CME in southern Europe and highlights the difficulties
      encountered by veterinarians to differentiate CME from other vector-borne
      diseases under field conditions.

PMID- 25561344
TI  - Enhanced activity of acetyl CoA synthetase adsorbed on smart microgel: an
      implication for precursor biosynthesis.
AB  - Acetyl coenzyme A (acetyl CoA) is an essential precursor molecule for synthesis
      of metabolites such as the polyketide-based drugs (tetracycline, mitharamycin,
      Zocor, etc.) fats, lipids, and cholesterol. Acetyl CoA synthetase (Acs) is one of
      the enzymes that catalyzes acetyl CoA synthesis, and this enzyme is essentially
      employed for continuous supply of the acetyl CoA for the production of these
      metabolites. To achieve reusable and a more robust entity of the enzyme, we
      carried out the immobilization of Acs on poly(N-isopropylacrylamide)
      poly(ethylenimine) (PNIPAm-PEI) microgels via adsorption. Cationic PNIPAm-PEI
      microgel was synthesized by one-step graft copolymerization of NIPAm and N,N
      methylene bis-acrylamide (MBA) from PEI. Adsorption studies of Acs on microgel
      indicated high binding of enzymes, with a maximum binding capacity of 286 MUg/mg
      of microgel for Acs was achieved. The immobilized enzymes showed improved
      biocatalytic efficiency over free enzymes, beside this, the reaction parameters
      and circular dichroism (CD) spectroscopy studies indicated no significant changes
      in the enzyme structure after immobilization. This thoroughly characterized
      enzyme bioconjugate was further immobilized on an ultrathin membrane to assess
      the same reaction in flow through condition. Bioconjugate was covalently
      immobilized on a thin layer of preformed microgel support upon polyethylene
      terephthalate (PET) track etched membrane. The prepared membrane was used in a
      dead end filtration device to monitor the bioconversion efficiency and
      operational stability of cross-linked bioconjugate. The membrane reactor showed
      consistent operational stability and maintained >70% of initial activity after 7
      consecutive operation cycles. 

PMID- 25561345
TI  - Cyclodextrin glycosyltransferase production by free cells of Bacillus circulans
      DF 9R in batch fermentation and by immobilized cells in a semi-continuous
      process.
AB  - Cyclodextrin glycosyltransferase (CGTase) catalyzes starch conversion into cyclic
      or linear oligosaccharides, important industrial products for the complexation of
      non-polar substances. In this work, conditions to increase CGTase production from
      Bacillus circulans strain DF 9R were optimized by two systems. On one hand, free
      cells were grown in batch fermentation experiments to optimize aeration and pH.
      The highest activity (1.47 +/- 0.21 U ml(-1)) was achieved after 48 h of growth,
      aeration of 1.5 vvm and pH regulated to 7.6. On the other hand, bacterial cells
      were immobilized on loofa and synthetic sponge, and used for CGTase production in
      a semi-continuous process. An initial biomass of 30 mg of lyophilized cells and
      an immobilization time of 24 h with loofa or synthetic sponge were enough to
      achieve increased production of CGTase: 0.91 +/- 0.10 and 0.95 +/- 0.11 U ml(-1),
      respectively. Sponges with immobilized bacteria were reused in 12 successive
      cycles. Besides, in our conditions, CGTase was not adsorbed onto the supports
      used for immobilization, which ensured the total recovery of the enzyme from the
      culture medium. The two CGTase production processes studied showed similar
      productivity and could be potentially scaled up.

PMID- 25561346
TI  - Industrial vitamin B12 production by Pseudomonas denitrificans using maltose
      syrup and corn steep liquor as the cost-effective fermentation substrates.
AB  - The aerobic Pseudomonas denitrificans is widely used for industrial and
      commercial vitamin B12 fermentation, due to its higher productivity compared to
      the anaerobic vitamin B12-producing microorganisms. This paper aimed to develop a
      cost-effective fermentation medium for industrial vitamin B12 production by P.
      denitrificans in 120,000-l fermenter. It was found that maltose syrup (a low-cost
      syrup from corn starch by means of enzymatic or acid hydrolysis) and corn steep
      liquor (CSL, a by-product of starch industry) were greatly applicable to vitamin
      B12 production by P. denitrificans. Under the optimal fermentation medium
      performed by response surface methodology, 198.27 +/- 4.60 mg/l of vitamin B12
      yield was obtained in 120,000-l fermenter, which was close to the fermentation
      with the refined sucrose (198.80 mg/l) and was obviously higher than that
      obtained under beet molasses utilization (181.75 mg/l). Therefore, maltose syrups
      and CSL were the efficient and economical substrates for industrial vitamin B12
      fermentation by P. denitrificans.

PMID- 25561347
TI  - Endometrial scratching for women with previous IVF failure undergoing IVF
      treatment.
AB  - The purpose of this study was to find out whether endometrial scratching could
      improve live birth rate in women with previous IVF failure undergoing fresh IVF
      cycle. In a randomized controlled trial, 387 women with previous IVF failure were
      divided into two groups. Group A (193 women) was subjected to endometrial biopsy
      procedure twice. Group B (194 women) was subjected to a placebo procedure. Our
      results showed no difference in live birth rate between the two groups of women
      (47.2% versus 38.1%, p = 0.08). However, regression analysis revealed that
      endometrial scratching was an independent predictor of live birth in the subgroup
      of women with two or more previous failure after control of other independent
      predictors (odds ratio (OR) 3.4, p = 0.005). We conclude that endometrial
      scratching does not improve live birth rate in women undergoing IVF treatment
      with previous one IVF failure. Nevertheless, it may improve live birth in women
      with two or more previous IVF failures.

PMID- 25561348
TI  - Causes of early death in multiple myeloma patients who are ineligible for high
      dose therapy with hematopoietic stem cell support: A study based on the
      nationwide Danish Myeloma Database.

PMID- 25561350
TI  - Dosing algorithm revisit for busulfan following IV infusion.
AB  - PURPOSE: Busulfan (Bu) exposure is critical for efficacy and safety. Body weight
      (BW), or adjusted ideal body weight (AIBW)-based dosing (WBD) algorithm, has been
      used in hematopoietic stem cell transplantation (HSCT). A recently completed
      phase 2 study revealed that 33.6 % of the subjects were under-, or over-exposed,
      with this WBD algorithm. This paper was to investigate Bu dosing algorithm in an
      attempt to improve the suboptimal Bu exposure. METHODS: Population PK modeling
      was conducted using the data from 207 patients. Dosing algorithm was developed
      based on derived covariate model of CL. Model-based simulation was conducted to
      assist test PK study design. A simplified CL estimation method was proposed based
      on the PK structure model for Bu. RESULTS: A one-compartment structure model
      adequately described the PK profile of Bu following an IV infusion. BSA best
      described the inter-individual variability of CL. The proposed dosing algorithm
      was dose (mg) = (31.7 * BSA - 11.6) * target AUC [uM min]/1,000. With this dosing
      algorithm, 14.3 % patients could be under- or over-exposed. A test PK study with
      reduced study duration and three PK samples can provide as nearly as good an
      estimate of CL compared to 12 PK samples on two different occasions. CONCLUSION:
      The proposed dosing algorithm can significantly improve the sub-exposure of Bu. A
      shortened test PK study duration with reduced PK samples can provide as near as
      good estimate for Bu CL. A simplified CL estimation method is valid.

PMID- 25561349
TI  - Delinking resident duty hours from patient safety.
AB  - Patient safety is a powerful motivating force for change in modern medicine, and
      is often cited as a rationale for reducing resident duty hours. However, current
      data suggest that resident duty hours are not significantly linked to important
      patient outcomes. We performed a narrative review and identified four potential
      explanations for these findings. First, we question the relevance of resident
      fatigue in the creation of harmful errors. Second, we discuss factors, including
      workload, experience, and individual characteristics, that may be more important
      determinants of resident fatigue than are duty hours. Third, we describe
      potential adverse effects that may arise from--and, therefore, counterbalance any
      potential benefits of--duty hour reductions. Fourth, we explore factors that may
      mitigate any risks to patient safety associated with using the services of
      resident trainees. In summary, it may be inappropriate to justify a reduction in
      working hours on the grounds of a presumed linkage between patient safety and
      resident duty hours. Better understanding of resident-related factors associated
      with patient safety will be essential if improvements in important patient safety
      outcomes are to be realized through resident-focused strategies.

PMID- 25561351
TI  - Dominant short repeated sequences in bacterial genomes.
AB  - We use a novel multidimensional searching approach to present the first
      exhaustive search for all possible repeated sequences in 166 genomes selected to
      cover the bacterial domain. We found an overrepresentation of repeated sequences
      in all but one of the genomes. The most prevalent repeats by far were related to
      interspaced short palindromic repeats (CRISPRs)-conferring bacterial adaptive
      immunity. We identified a deep branching clade of thermophilic Firmicutes
      containing the highest number of CRISPR repeats. We also identified a high
      prevalence of tandem repeated heptamers. In addition, we identified GC-rich
      repeats that could potentially be involved in recombination events. Finally, we
      identified repeats in a 16322 amino acid mega protein (involved in biofilm
      formation) and inverted repeats flanking miniature transposable elements (MITEs).
      In conclusion, the exhaustive search for repeated sequences identified new
      elements and distribution of these, which has implications for understanding both
      the ecology and evolution of bacteria.

PMID- 25561352
TI  - Distributions of allele combination in single and cross loci among patients with
      several kinds of chronic diseases and the normal population.
AB  - Genetic research has progressed along with scientific and technological
      developments. However, it is difficult to identify frequency differences in a
      particular allele distribution at a single locus. Such differences can be
      identified by examining the allele combination distribution. We explored
      different mathematical methods for statistical analyses to assess the association
      between the genotype and phenotype. We investigated the frequency distributions
      of alleles, combinations of single-locus genes, and combinations of cross-loci
      genes at 15 loci using 447 blood samples of 200 normal subjects, 72 patients with
      chronic obstructive pulmonary resistance, 50 liver cancers, 75 stomach cancers
      and 50 hematencephalon and identified each population as having a unique gene
      distribution and that the distribution followed certain rules. The probability of
      illness followed different rules and had apparent specificity. Differences
      obtained using statistics of combinations of cross-loci genes are superior to
      single-locus gene statistics, and combinations of single-locus gene statistics
      are better than allelic statistics. 

PMID- 25561354
TI  - Determination of key parameters for a mechanism-based model to predict
      Doxorubicin release from actively loaded liposomes.
AB  - Despite extensive study of liposomal drug formulations, reliable predictive
      models of release kinetics in vitro and in vivo are still lacking. Progress in
      the development of robust, predictive release models has been hindered by a lack
      of systematic, quantitative characterization of these complex drug delivery
      systems with respect to the myriad of factors that may influence drug release
      kinetics and the wide range of dissolution media/methods employed to monitor
      release. In this paper, the key processes and parameters needed to develop a
      complete mechanism-based model for doxorubicin release from actively loaded
      liposomal formulations resembling Doxil((r)) are determined. Quantitative models
      must account for the driving force(s) [i.e., activity gradient(s) of the
      permeable species between the intraliposomal and external media] and the
      permeability-area product(s) for lipid bilayer transport. These factors are
      intertwined as membrane permeability-area products require knowledge of the drug
      species and concentrations that account for the release. The necessary
      information includes values for the drug pKa, identity of the permeable species
      and species permeability coefficients, a model to describe drug self-association
      and the relevant equilibrium constant(s), the bilayer/water partition coefficient
      of the predominant drug species under relevant pH conditions, and the solubility
      product (Ksp ) for intraliposomal precipitates that exist in such formulations.

PMID- 25561355
TI  - Does a barcoding gap exist in prokaryotes? Evidences from species delimitation in
      cyanobacteria.
AB  - The amount of information that is available on 16S rRNA sequences for prokaryotes
      thanks to high-throughput sequencing could allow a better understanding of
      diversity. Nevertheless, the application of predetermined threshold in genetic
      distances to identify units of diversity (Operative Taxonomic Units, OTUs) may
      provide biased results. Here we tests for the existence of a barcoding gap in
      several groups of Cyanobacteria, defining units of diversity according to clear
      differences between within-species and among-species genetic distances in 16S
      rRNA. The application of a tool developed for animal DNA taxonomy, the Automatic
      Barcode Gap Detector (ABGD), revealed that a barcoding gap could actually be
      found in almost half of the datasets that we tested. The identification of units
      of diversity through this method provided results that were not compatible with
      those obtained with the identification of OTUs with threshold of similarity in
      genetic distances of 97% or 99%. The main message of our results is a call for
      caution in the estimate of diversity from 16S sequences only, given that
      different subjective choices in the method to delimit units could provide
      different results. 

PMID- 25561356
TI  - Catalyst-controlled chemoselective reaction of 3-indolylmethanols with cyclic
      enaminones leading to C2-functionalized indoles.
AB  - A catalyst-controlled chemoselective formal 1,2-addition of 3-indolylmethanols
      with cyclic enaminones has been established in the presence of TfOH as a strong
      acid, which afforded C2-functionalized indole derivatives in generally good
      yields (up to 89% yield). This reaction not only confronted the great challenge
      in 1,2-addition of 3-indolylmethanols but also provided a good strategy for C2
      functionalization of indole derivatives. The investigation on the reaction
      mechanism revealed that this formal 1,2-addition included a tandem sequence of
      1,4-addition/[1,3]-C migration/isomerization, in which the [1,3]-C migration of
      the 1,4-addition product was a key step and the acidity of the catalyst played a
      decisive role in the observed chemoselectivity. 

PMID- 25561357
TI  - Congestion analysis to evaluate the efficiency and appropriateness of hospitals
      in Sicily.
AB  - Over the past twenty years, important changes in the Italian National Health
      System have been made in order to obtain significant improvements in the
      efficiency, appropriateness and quality of health care delivery, while reducing
      health expenditure. In this paper we proposed a multidimensional approach to
      assess the impact of organization inappropriateness on the efficiency evaluation
      of hospitals in Sicily for the year 2009. This study was based on cross-sectional
      data for 116 (out of 129) short-term, acute-care hospitals. The analysis
      considered beds, physicians, nurses and other personnel as inputs, ordinary
      discharges and day-hospital admissions as desirable outputs and inappropriate
      discharges and day-hospitals as undesirable outputs of the health care process.
      We refer to output-congestion to measure the loss of desirable outcome, which is
      related to the simultaneous occurrence of inappropriateness. The main findings of
      our analysis indicate that most of the measured overall inefficiency of Sicilian
      hospitals could be attributed to congestion and pure technical inefficiency and
      that congestion was statistically different among hospital trusts, local public
      hospitals and for-profit hospitals and along the provinces. In Sicily,
      significant shares of inputs are still employed to supply inappropriate care,
      with the effect of producing less desirable health care outcomes than expected. 

PMID- 25561358
TI  - Cognitive training as a resolution for early executive function difficulties in
      children with intellectual disabilities.
AB  - Core executive functions (EF) such as attention, and working memory have been
      strongly associated with academic achievement, language development and
      behavioral stability. In the case of children who are vulnerable to cognitive and
      learning problems because of an underlying intellectual disability, EF
      difficulties will likely exacerbate an already compromised cognitive system. The
      current review examines cognitive training programs that aim to improve EF,
      specifically focusing on the potential of this type of intervention for children
      who have intellectual disabilities. We conclude that despite considerable
      discrepancies regarding reported intervention effects, these inconsistencies can
      be attributed to flaws in both program and study design. We discuss the steps
      needed to address these limitations and to facilitate the advancement of non
      pharmaceutical interventions for children with intellectual disabilities. 

PMID- 25561359
TI  - Effects of physical activity on executive function and motor performance in
      children with ADHD.
AB  - Children with Attention-Deficit/Hyperactivity Disorder (ADHD) often show major
      deficits in motor and cognitive abilities. Pharmacological treatment is commonly
      used to reduce ADHD symptoms. However, non-pharmacologic treatment methods would
      be preferred by parents, children and psychiatrists. Physical activity (PA) has
      been demonstrated to improve cognitive functioning in healthy populations. It can
      be hypothesized that there are similar beneficial effects in children with ADHD,
      however, very little is known about this issue. The purpose of the present study
      was to determine whether PA improves cognitive performance in children with ADHD.
      A total of 43 children with ADHD (32 boys and 11 girls) aged between seven and 12
      years took part in the study. To investigate whether potential effects on
      executive functioning depend on the kind of PA, two different 12-week training
      programs were implemented. The study-design consisted of two experimental groups
      (EG1, n=13; EG2, n=14) and a wait-list control group (CG, n=16). Participants in
      EG1 took part in a training which focused on the abilities ball handling, balance
      and manual dexterity. Participants in EG2 group were trained in sports without a
      specific focus. The children in the CG group received no intervention.
      Participants completed assessments of working memory (WM) and motor performance
      before, immediately after the first training week and one week after the last
      session. After the 12-week intervention period, several measures of the EG1 and
      EG2s significantly improved over time. Furthermore, between group comparisons
      demonstrated significant improvements in both EG1 and EG2 compared to the CG in
      variables assessing WM performance and motor performance. These findings support
      the hypothesis that long-term PA has a positive effect on executive functions of
      children with ADHD, regardless of the specificity of the PA. The outcomes
      indicated that regular PA can be used as a complementary or alternative non
      pharmacologic treatment for ADHD. 

PMID- 25561360
TI  - Evaluating relationships between symptom duration and persistence of rheumatoid
      arthritis: does a window of opportunity exist? Results on the Leiden early
      arthritis clinic and ESPOIR cohorts.
AB  - BACKGROUND: A prolonged symptom or disease duration at treatment initiation is
      associated with unfavourable outcomes in rheumatoid arthritis (RA). It is unknown
      whether this relation is linear, referring to a common 'the-earlier-the-better
      principle', or whether a transient time frame in which the disease is more
      susceptible to treatment exists, referring to a 'window of opportunity'. To
      elucidate this, we evaluated the shape of the associations of symptom duration
      with persistence of RA. METHODS: Patients with 1987 RA treated with disease
      modifying antirheumatic drugs (DMARDs) in the Leiden Early Arthritis Clinic (EAC,
      n=738) and Evaluation et Suivi de POlyarthrites Indifferenciees Recentes (ESPOIR)
      (n=533) were studied. Cox proportional hazards regression models using natural
      cubic splines were performed; the log-HR on DMARD-free sustained remission (the
      opposite of RA persistence) during 5-year follow-up was plotted against symptom
      duration. Discrimination was measured using time-dependent receiver operator
      characteristic curves. Subanalyses were performed stratified for the DMARDs used
      (methotrexate or other conventional DMARDs) and for anticitrullinated peptide
      antibody (ACPA). RESULTS: 11.5% (85/738) and 5.4% (29/533) of EAC and ESPOIR RA
      patients achieved DMARD-free sustained remission. In both cohorts and all
      analyses, the curves depicting the log-HRs on remission in relation to symptom
      duration were not linear. The symptom duration with optimal discriminative
      ability was 14.9 weeks (95% CI 12.3 to 16.0; area under the curve (AUC) 0.61) in
      the EAC and 19.1 weeks (95% CI 12.3 to 28.0; AUC 0.59) in ESPOIR. For ACPA
      positive RA, this was 11.4 weeks (95% CI 7.7 to 79.0; AUC 0.56) and for ACPA
      negative RA 15.0 weeks (95% CI 9.7 to 48.7; AUC 0.56). CONCLUSIONS: The
      association between symptom duration and RA persistence is not linear, suggesting
      the presence of a confined period in which RA is more susceptible to treatment.

PMID- 25561361
TI  - Effectiveness and safety of tocilizumab therapy for patients with rheumatoid
      arthritis and renal insufficiency: a real-life registry study in Japan (the ACTRA
      RI study).

PMID- 25561363
TI  - c-Abl induces stabilization of histone deacetylase 1 (HDAC1) in a kinase activity
      dependent manner.
AB  - c-Abl is a non-receptor-type tyrosine kinase that regulates various cellular
      events, including cell proliferation, differentiation, and apoptosis, through
      phosphorylation of cytoplasmic and nuclear targets. Although we showed that c-Abl
      induces histone deacetylation, the molecular mechanisms of this phenomenon are
      largely unknown. Here, we analyzed the effect of c-Abl on the expression of
      histone deacetylase 1 (HDAC1), because c-Abl was shown to be involved in
      maintenance of nuclear protein levels of HDAC1. Co-transfection of HDAC1 with c
      Abl increased the levels of HDAC1 protein in a kinase activity-dependent manner
      without affecting its mRNA levels. Treatment with the proteasome inhibitor MG132
      increased protein levels of HDAC1 in cells transfected with HDAC1 but not in
      cells co-transfected with HDAC1 and c-Abl. Among class I HDACs, knockdown of
      endogenous c-Abl preferentially suppressed endogenous protein levels of HDAC1,
      suggesting that c-Abl stabilizes HDAC1 protein by inhibiting its proteasomal
      degradation. Subcellular fractionation showed that the stabilization of HDAC1 by
      c-Abl occurred in the nucleus. Despite the fact that HDAC1 was phosphorylated by
      co-expression with c-Abl, stabilization of HDAC1 by c-Abl was not affected by
      mutations in its sites phosphorylated by c-Abl. Co-expression with HDAC1 and
      nuclear-targeted c-Abl did not affect HDAC1 stabilization. Therefore, these
      results suggest that c-Abl induces HDAC1 stabilization possibly through
      phosphorylation of a cytoplasmic target that is involved in proteasomal
      degradation of HDAC1. 

PMID- 25561364
TI  - Connective tissue diseases: Adipocyte-myofibroblast transition: linking
      intradermal fat loss to skin fibrosis in SSc.

PMID- 25561362
TI  - The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal
      anti-inflammatory drugs and corticosteroids on cardiovascular events in
      rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and
      meta-analysis.
AB  - The objective of this systematic literature review was to determine the
      association between cardiovascular events (CVEs) and antirheumatic drugs in
      rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso).
      Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases
      (1960 to December 2012) and proceedings from major relevant congresses (2010
      2012) for controlled studies and randomised trials reporting confirmed CVEs in
      patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta
      analyses were performed on extracted data. Out of 2630 references screened, 34
      studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all
      CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR),
      0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to
      0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk
      of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been
      specifically related to the effects of rofecoxib. Corticosteroids increased the
      risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic
      therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003).
      In RA, tumour necrosis factor inhibitors and methotrexate are associated with a
      decreased risk of all CVEs while corticosteroids and NSAIDs are associated with
      an increased risk. Targeting inflammation with tumour necrosis factor inhibitors
      or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso,
      limited evidence suggests that systemic therapies are associated with a decrease
      in all CVE risk. 

PMID- 25561366
TI  - Paediatric rheumatology in 2014: Digging deeper for greater precision and more
      impact in JIA.
AB  - Optimizing the management of childhood arthritis requires detailed knowledge of
      the disease in an individual patient. Advances in 2014 show how in-depth genetic
      studies and insights into immunopathogenesis could translate into clinical
      biomarkers and, eventually, individualized therapy.

PMID- 25561365
TI  - Management of juvenile idiopathic arthritis: hitting the target.
AB  - The treatment of juvenile idiopathic arthritis (JIA) is evolving. The growing
      number of effective drugs has led to successful treatment and prevention of long
      term sequelae in most patients. Although patients with JIA frequently achieve
      lasting clinical remission, sustained remission off medication is still elusive
      for most. Treatment approaches vary substantially among paediatric
      rheumatologists owing to the inherent heterogeneity of JIA and, until recently,
      to the lack of accepted and well-evidenced guidelines. Furthermore, many
      pertinent questions related to patient management remain unanswered, in
      particular regarding treatment targets, and selection, intensity and sequence of
      initiation or withdrawal of therapy. Existing JIA guidelines and recommendations
      do not specify treat-to-target or tight control strategies, in contrast to adult
      rheumatology in which these approaches have been successful. The concepts of
      window of opportunity (early treatment to improve long-term outcomes) and
      immunological remission (abrogation of subclinical disease activity) are also
      fundamental when defining treatment methodologies. This Review explores the
      application of these concepts to JIA and their possible contribution to the
      development of future clinical guidelines or consensus treatment protocols. The
      article also discusses how diverse forms of standardized, guideline-led care and
      personalized treatment can be combined into a targeted, patient-centred approach
      to optimize management strategies for patients with JIA. 

PMID- 25561367
TI  - Osteoimmunology in 2014: Two-faced immunology-from osteogenesis to bone
      resorption.
AB  - Even though activation of immunity is associated with bone destruction, new
      mechanisms have been described in 2014 through which immunology-associated
      pathways can cooperate to support osteogenesis. These advances support the view
      of the immune system as a central mechanism which can regulate bone homeostasis,
      regeneration and destruction.

PMID- 25561368
TI  - Systemic sclerosis in 2014: Advances in cohort enrichment shape future of trial
      design.
AB  - The treatment and study of systemic sclerosis (SSc) is entering a new era with
      the reporting and preparation of several randomized controlled trials according
      to an improved understanding of SSc pathogenesis. Advances in trial designs
      reported in 2014 should now be built upon with further improvements to patient
      selection to enable targeting of therapies to specific subgroups of patients with
      SSc.

PMID- 25561369
TI  - Adrenergic modulation of migration, CD11b and CD18 expression, ROS and
      interleukin-8 production by human polymorphonuclear leukocytes.
AB  - OBJECTIVES: Adrenergic modulation of immunity has been extensively characterized,
      however, few information exist regarding polymorphonuclear leukocytes (PMN),
      despite their key role in immunity and inflammation. We investigated the effect
      of adrenergic agents on human PMN migration, CD11b and CD18 expression, reactive
      oxygen species (ROS) and interleukin (IL)-8 production, and on adrenoceptor (AR)
      expression. METHODS: Migration was measured by the Boyden chamber assay,
      CD11b/CD18 expression was assessed by flow cytometry, intracellular ROS were
      detected by spectrofluorimetry, and IL-8 was quantitated by standard ELISA assay.
      AR mRNA levels were measured by real-time PCR and PMN morphology was studied by
      scanning electron microscopy. RESULTS: Adrenaline(A), noradrenaline and the beta
      AR agonist isoprenaline reduced N-formyl-Met-Leu-Phe (fMLP)-induced migration,
      CD11b/CD18 expression, and ROS production, without affecting IL-8. The effect of
      A on CD11b was antagonized by yohimbine and propranolol, and increased by
      prazosin. The effect on ROS production was completely abolished by propranolol.
      PMN expressed alpha(1A)-, alpha(1B)-, alpha(1D)-, alpha(2A)-, alpha(2C)-, beta(1)
      , beta(2)-, and beta(3)-AR mRNA. A prevented fMLP-induced morphological changes
      of PMN. CONCLUSIONS: Adrenergic agents reduced PMN responses mainly through beta
      AR, although alpha-AR may contribute at least to CD11b expression. AR-operated
      pathways in PMN should be investigated in disease conditions and in the response
      to therapeutic agents.

PMID- 25561370
TI  - Disease control and treatment modalities have impact on quality of life in
      acromegaly evaluated by Acromegaly Quality of Life (AcroQoL) Questionnaire.
AB  - Various factors influence quality of life (QoL) in acromegaly. Whether disease
      control and treatment approach are related to QoL is still a matter of debate.
      The aim of the present study was to evaluate QoL in patients with acromegaly
      using the disease-specific Acromegaly Quality of Life Questionnaire in respect to
      disease activity, treatment modalities, and other factors. We studied 212
      patients with acromegaly in a cross-sectional manner over a 6-year period in a
      single tertiary center. As a second step, seventy of the patients who were with
      active disease at baseline were followed up prospectively and 45 of them were in
      remission at re-evaluation. In regard to the cross-sectional group, active
      acromegaly independently predicted worse appearance scores. Prior radiotherapy
      and older age were independent negative predictors of all scales. Female gender
      negatively predicted all scales except the appearance domain. Longer duration of
      remission predicted worse personal relations scores in biochemically controlled
      patients. The use of somatostatin analog (SSA) was associated with worse personal
      relations scores, while higher IGF-1 index predicted worse appearance scores in
      patients with active acromegaly. In the prospective group, achievement of
      remission independently predicted improvement of the total scale. Lower
      corresponding baseline scores predicted improvement of the total, physical, and
      appearance scales, while the absence of hypopituitarism independently predicted
      improvement of the appearance scale. The use of SSA was associated with
      improvement of the total and appearance scores. In conclusion, QoL is a
      multifactorial issue that needs an individualized approach for detection and
      management. 

PMID- 25561372
TI  - Energy efficient glazing for adaptive solar control fabricated with
      photothermotropic hydrogels containing graphene oxide.
AB  - Glazing for adaptive solar control is the most promising for energy efficient
      development, because the use of this technology in buildings can be expected to
      significantly impact energy use and efficiency by screening sunlight that enters
      a building in summer. To achieve autonomous adjustable transparency, we have
      developed photothermotropic material system by combining photothermal materials
      with thermotropic hydrogels. We found that graphene oxide dispersed within a
      hydrogel matrix effectively converts the photo energy of sunlight into thermal
      energy, providing the efficient means to trigger transparency of thermotropic
      hydrogels. Therefore, we could develop switchable glazing of novel
      photothermotropic mechanism that screen strong sunlight and heat radiation in
      response to the sunlight intensity, as well as the temperature. Furthermore, in
      this study, a prototype device was manufactured with developed materials and
      successfully operated in outdoor testing. 

PMID- 25561371
TI  - Reduced plasma level of diazepam-binding inhibitor (DBI) in patients with morbid
      obesity.

PMID- 25561373
TI  - Determinants of brain SPECT perfusion and connectivity in treatment-resistant
      depression.
AB  - This study aims to characterize and compare functional brain single photon
      emission tomography (SPECT) perfusion and connectivity in treatment-resistant
      depression (TRD) according to distinct demographic or clinical profiles (male vs.
      female; old vs. young; unipolar vs. bipolar) and to study their relationship to
      the severity and the duration of episode/illness. We retrospectively included 127
      consecutive patients who met DSM-IV criteria for a nonpsychotic major TRD
      episode. All patients were studied using (99m)Tc-ethyl cysteinate dimer SPECT.
      Whole-brain, voxel-based, between-groups analyses were performed according to
      demographic and clinical data and in comparison to 37 healthy subjects. Voxel
      wise interregional correlation was also performed to compare functional SPECT
      connectivity. Finally, relationships were searched for regarding severity and
      duration of episode/illness. The whole group of patients exhibited significant
      hypoperfusion within bilateral fronto-temporal, insular, and anterior cingulate
      cortices, as well as within the left caudate. Functional connectivity between
      left frontal and left cerebellar regions was higher in patients than in healthy
      subjects. Gender, age, and type of mood disorder did not influence these SPECT
      patterns. A significant relationship was found between brain SPECT perfusion and
      either duration or global severity of illness in particular frontal areas. Our
      data support the hypothesis of a shared SPECT pattern, whatever the profile of
      TRD, involving fronto-temporal regions and the cerebellum. 

PMID- 25561374
TI  - Neurostructural correlates of two subtypes of specific phobia: a voxel-based
      morphometry study.
AB  - The animal and blood-injection-injury (BII) subtypes of specific phobia are both
      characterized by subjective fear but distinct autonomic reactions to threat.
      Previous functional neuroimaging studies have related these characteristic
      responses to shared and non-shared neural underpinnings. However, no comparative
      structural data are available. This study aims to fill this gap by comparing the
      two subtypes and also comparing them with a non-phobic control group. Gray and
      white matter data of 33 snake phobia subjects (SP), 26 dental phobia subjects
      (DP), and 37 healthy control (HC) subjects were analyzed with voxel-based
      morphometry. Especially DP differed from HC and SP by showing significantly
      increased grey matter volumes in widespread areas including the right subgenual
      anterior cingulate gyrus, left insula, left orbitofrontal and left prefrontal
      (PFC) cortices. In addition, white matter volume was significantly increased in
      the left PFC in DP compared with SP. These results are in line with functional
      changes observed in dental phobia and point toward those brain circuits
      associated with emotional processing and regulation. Future studies should aim to
      further delineate functional and structural connectivity alterations in specific
      phobia. 

PMID- 25561375
TI  - WITHDRAWN: Precuneal and amygdala spontaneous activity and functional
      connectivity in war-zone-related PTSD.
AB  - This article has been withdrawn at the request of the author. The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 25561376
TI  - Magnetic resonance cisternogram with intrathecal gadolinium with delayed imaging
      for difficult to diagnose cerebrospinal fluid leaks of anterior skull base.
AB  - BACKGROUND: Workup of cerebrospinal fluid (CSF) leaks can be challenging.
      Patients with intermittent or infrequent clear rhinorrhea that cannot be
      collected, those with questionable or multiple skull-base (SB) defects on
      imaging, and those with previous SB surgery can present diagnostic dilemmas. In
      this patient population, radiologic studies that allow repeat imaging over hours
      to days can increase the diagnostic yield. We report our experience with magnetic
      resonance cisternogram with intrathecal gadolinium (MRCgGd) in this patient
      population. METHODS: This study was a retrospective review of patients who
      underwent MRCgGd for workup of suspected CSF leaks at a tertiary care academic
      center. RESULTS: Over the past 3 years, 11 patients (10 females; mean age 50
      years) underwent MRCgGd. Seven patients had suspected spontaneous CSF leaks from
      idiopathic intracranial hypertension and 2 had postsurgical defects. All patients
      had previous imaging that was indeterminate in localizing the site of the leak.
      Only 3 patients had positive beta-2 transferrin studies, all with multiple
      potential leak sites. MRCgGd confirmed the absence of leaks at 4 previously
      repaired SB defects, identified spinal canal leaks but no SB leaks in 2 patients
      (1 of whom had a nonleaking SB defect), and identified 5 patients with one or
      more SB leaks. Repeat imaging, from 30 minutes to 20 hours, was beneficial in
      identifying 4 leaks not confirmed in the immediate imaging, and ruling out leaks
      in 5 cases, therefore guiding further treatment. No complications occurred.
      CONCLUSION: MRCgGd is a useful diagnostic test in the workup of patients with
      difficult CSF leaks, with delayed imaging providing valuable diagnostic
      information.

PMID- 25561377
TI  - A matched case-control study of preterm birth in one hospital in Beijing, China.
AB  - BACKGROUND: Preterm birth is an unresolved global health issue. The etiologies of
      preterm birth are complex and multifactorial. To examine risk factors related to
      preterm birth, a matched case-control study was conducted in a hospital in
      Beijing, China where little data on preterm birth have been published in the
      scientific literature. METHODS: A 1:1 matched case-control study was conducted in
      172 pairs of women with preterm birth (case group) and term delivery (control
      group). Eligible subjects were interviewed in person by well-trained
      investigators using a questionnaire. Information on obstetric diagnosis and
      newborns were abstracted from inpatients' medical records. Univariate and
      multivariate conditional logistic regression models were used to measure the
      associations between related factors and preterm birth. RESULTS: Univariate
      analysis showed that 6 of 12 factors were associated with preterm birth.
      Multivariate results showed that gestational hypertension (OR = 7.76), low
      gestational weight gain (OR = 3.02), frequent prenatal care (OR = 0.16), balanced
      diet (OR = 0.36), and high gestational weight gain (OR = 0.41) were associated
      with preterm birth. CONCLUSION: This study provides information on preterm birth
      in Beijing, China, and it also lends support to existing evidence about the role
      of maternal nutritional status, prenatal care and gestational hypertension as
      risk factors for preterm birth.

PMID- 25561378
TI  - Neuropsychological performance before and after partial or complete insulectomy
      in patients with epilepsy.
AB  - Resection of the insular cortex is becoming more frequent as it is increasingly
      recognized that a nonnegligible proportion of surgical candidates with drug
      resistant epilepsy have an epileptogenic zone that involves the insula. In the
      last decades, however, the insula has been proposed to be involved in several
      neuropsychological functions, and there is a lack of documentation on whether
      partial or complete insulectomy results in permanent cognitive impairments in
      this clinical population. In this study, we conducted standard preoperative and
      postoperative neuropsychological assessments in 18 patients undergoing epilepsy
      surgery that included the removal of the insula in the right (n=13) or the left
      (n=5) hemisphere. Postoperative testing was conducted at least five months after
      surgery. Cognitive impairments were common and heterogeneous prior to surgery,
      with language and verbal memory impairments being especially frequent among
      patients in whom epileptic seizures originated from the left hemisphere. After
      surgery, declines and improvements occurred on a variety of outcomes, although
      new deficits were relatively infrequent among patients who had obtained normal
      performance at baseline. Statistical comparisons between preoperative and
      postoperative assessments revealed significant deterioration of only one outcome 
      the color naming condition of the Stroop test - which relies on oro-motor speed
      and lexical access. These findings suggest that partial or complete resection of
      the insular cortex in patients with drug-refractory epilepsy can be conducted
      without major permanent neuropsychological impairments in a vast majority of
      patients. However, small decrements in specific cognitive functions can be
      expected, which should also be taken into account when considering the surgical
      option in this clinical population. 

PMID- 25561379
TI  - An evaluation of the impact of memory and mood on antiepileptic drug adherence.
AB  - RATIONALE: Antiepileptic drugs are the mainstay of treatment for patients with
      epilepsy. Adherence to the prescribed regimen is a major factor in achieving a
      reduced seizure burden, which can decrease morbidity and mortality. Patients with
      epilepsy oftentimes complain about difficulty with memory. Because little is
      known about the relationship between memory and mood and adherence, the purpose
      of this project was to determine the impact of the confounding factors of memory
      and mood on antiepileptic drug adherence in patients with epilepsy. METHODS: One
      hundred adult patients with epilepsy were recruited from the outpatient neurology
      clinic for this cross-sectional study. Patients who met the inclusion criteria
      completed measures of subjective memory (subset of 6 memory questions from the
      QOLIE-89) and objective memory (Hopkins Verbal Learning Test - Revised),
      subjective adherence (Morisky scale) and objective adherence (medication
      possession ratio), and mood (Neurological Disorders Depression Inventory for
      Epilepsy). Refill records from each patient's community pharmacy were used to
      objectively assess adherence. Medication possession ratios were calculated based
      on the antiepileptic drug refill records over the previous 6months. Patients were
      considered adherent if their MPR was >80%. RESULTS: Women made up the majority of
      the sample (n=59), and, on average, patients had been living with epilepsy for
      nearly 20years. Approximately 40% of the sample were on antiepileptic drug
      monotherapy; most patients (>70%) took their antiepileptic drugs twice daily, and
      the mean number of total medications was 4.25+/-2.98. Based on the objective
      measure of adherence, 35% of the patients were nonadherent. Patients self
      reported better adherence than what was objectively measured. Only the retention
      metric of the objective memory measure differentiated adherent patients from
      nonadherent patients. Patients in the adherent group had significantly lower
      depression scores (indicating better mood) compared with those in the nonadherent
      group (p=0.04). CONCLUSIONS: Objective memory measures were not robustly
      correlated with adherence. However, we observed that patients with higher
      depressed mood scores were more likely to be nonadherent. By targeting patients
      with epilepsy and comorbid depression, practitioners may identify patients at
      greatest risk of nonadherence and subsequent harm.

PMID- 25561380
TI  - Application of envelope trend to analyze early EEG changes in the frontal regions
      during intracarotid amobarbital procedure in children.
AB  - BACKGROUND: Intracarotid amobarbital procedure (IAP) is acknowledged as the gold
      standard test for language lateralization. EEG is performed routinely during IAP
      to monitor the anesthetization of a brain hemisphere. Here, we studied the
      correlation between the early EEG changes using envelope trend and the clinical
      outcome of IAP. METHOD: Fifty consecutive patients underwent IAP at Texas
      Children's Hospital (2004-2009). Intracarotid amobarbital procedure was
      considered "complete" or "incomplete" based on the outcome if the procedure was
      completed or aborted due to behavior changes. Envelope trend was used to
      calculate the median EEG amplitude changes within the first 60s of IAP.
      Statistical analysis was performed to determine the role of EEG changes and
      clinical features on the procedure outcome. RESULTS: Only 30 IAP-EEG files were
      available for review. Amobarbital was administered at the dose of 60-150mg (mean:
      110+/-20). The intracarotid amobarbital procedure was recorded as complete in 23
      patients and incomplete in 7 patients. EEG changes occurred within the first few
      seconds following amobarbital injection. Following amobarbital injection, focal
      slowing was present in the ipsilateral frontal region or both ipsilateral and
      contralateral frontal regions. Elapsed time to the first EEG change or duration
      and change in median EEG amplitude in the ipsilateral frontal regions were
      indifferent between the complete and incomplete groups (p>0.05). However, the
      median amplitude changes between the ipsilateral and contralateral frontal
      regions within each group were found significant only in the complete group
      (p<0.05), suggesting ipsilateral without contralateral frontal slowing. Other
      than age at the time of IAP (p=0.03), none of the other clinical features
      correlated with the clinical outcome of IAP (p>0.05). CONCLUSION: Early EEG
      changes during IAP using envelope trend may predict successful completion of the
      IAP test. Younger children are at risk of behavioral changes during IAP.

PMID- 25561381
TI  - Folate use in women with epilepsy: predictors of adherence in a specialized
      tertiary outclinic.
AB  - PURPOSE OF THE STUDY: The aims of this study were to determine the percentage of
      women with epilepsy (WWE) taking folic acid (FA) in an outpatient epilepsy
      tertiary hospital at Sao Paulo, Brazil, and to identify the possible predictors
      of adherence. METHOD: Five hundred seventy-six medical records of patients
      followed in our service were reviewed. Sixty-six WWE using antiepileptic drugs
      with age between 16 and 52, sexually active but not in menopausal period, not
      pregnant, and not sterilized or with vasectomized partners underwent direct
      interviews with a prestructured questionnaire. Logistic regression with clinical
      and demographic variables using a stepwise method was performed to identify
      predictable variables of folate use. RESULTS: We found 42.40% of FA intake.
      Hormonal contraceptive method use was an independent variable negatively
      associated with adherence to folate. Additionally, educational level was an
      independent variable positively associated with adherence to folate in WWE above
      35years of age. CONCLUSION: We found low folate adherence. Improved planning pre
      conception for WWE should improve rates of effective folate supplementation.

PMID- 25561383
TI  - Integrating Gene Transcription-Based Biomarkers to Understand Desert Tortoise and
      Ecosystem Health.
AB  - Tortoises are susceptible to a wide variety of environmental stressors, and the
      influence of human disturbances on health and survival of tortoises is difficult
      to detect. As an addition to current diagnostic methods for desert tortoises, we
      have developed the first leukocyte gene transcription biomarker panel for the
      desert tortoise (Gopherus agassizii), enhancing the ability to identify specific
      environmental conditions potentially linked to declining animal health. Blood
      leukocyte transcript profiles have the potential to identify physiologically
      stressed animals in lieu of clinical signs. For desert tortoises, the gene
      transcript profile included a combination of immune or detoxification response
      genes with the potential to be modified by biological or physical injury and
      consequently provide information on the type and magnitude of stressors present
      in the animal's habitat. Blood from 64 wild adult tortoises at three sites in
      Clark County, NV, and San Bernardino, CA, and from 19 captive tortoises in Clark
      County, NV, was collected and evaluated for genes indicative of physiological
      status. Statistical analysis using a priori groupings indicated significant
      differences among groups for several genes, while multidimensional scaling and
      cluster analyses of transcription C T values indicated strong differentiation of
      a large cluster and multiple outlying individual tortoises or small clusters in
      multidimensional space. These analyses highlight the effectiveness of the gene
      panel at detecting environmental perturbations as well as providing guidance in
      determining the health of the desert tortoise. 

PMID- 25561384
TI  - Role of social support in adolescent suicidal ideation and suicide attempts.
AB  - PURPOSE: The present study examined the relative contributions of perceptions of
      social support from parents, close friends, and school on current suicidal
      ideation (SI) and suicide attempt (SA) history in a clinical sample of
      adolescents. METHODS: Participants were 143 adolescents (64% female; 81% white;
      range, 12-18 years; M = 15.38; standard deviation = 1.43) admitted to a partial
      hospitalization program. Data were collected with well-validated assessments and
      a structured clinical interview. Main and interactive effects of perceptions of
      social support on SI were tested with linear regression. Main and interactive
      effects of social support on the odds of SA were tested with logistic regression.
      RESULTS: Results from the linear regression analysis revealed that perceptions of
      lower school support independently predicted greater severity of SI, accounting
      for parent and close friend support. Further, the relationship between lower
      perceived school support and SI was the strongest among those who perceived lower
      versus higher parental support. Results from the logistic regression analysis
      revealed that perceptions of lower parental support independently predicted SA
      history, accounting for school and close friend support. Further, those who
      perceived lower support from school and close friends reported the greatest odds
      of an SA history. CONCLUSIONS: Results address a significant gap in the social
      support and suicide literature by demonstrating that perceptions of parent and
      school support are relatively more important than peer support in understanding
      suicidal thoughts and history of suicidal behavior. Results suggest that
      improving social support across these domains may be important in suicide
      prevention efforts.

PMID- 25561382
TI  - Monitoring Antibiotic Use and Residue in Freshwater Aquaculture for Domestic Use
      in Vietnam.
AB  - Vietnam is an important producer of aquaculture products, and aquatic products
      are essential to the Vietnamese diet. However, Vietnam also has very little
      enforced regulation pertaining to antibiotic usage in domestic aquaculture, which
      raises concerns for antibiotic resistance in pathogenic bacteria. In this study,
      analysis was conducted on the presence of antibiotic residues in domestically
      sold fish and shrimp raised in freshwater farms in Vietnam, and an assessment of
      farmers' knowledge of proper antibiotics usage was performed. The results
      indicated that a quarter of tested aquaculture products were antibiotic screening
      test positive, and there is a general lack of knowledge about the purpose and
      proper usage of antibiotics by aquaculture producers. Farmers' decision-making
      processes about antimicrobial use are influenced by biased sources of
      information, such as drug manufacturers and sellers, and by financial incentives.

PMID- 25561385
TI  - Dependence levels in users of electronic cigarettes, nicotine gums and tobacco
      cigarettes.
AB  - OBJECTIVE: To assess dependence levels in users of e-cigarettes, and compare them
      with dependence levels in users of nicotine gums and tobacco cigarettes. DESIGN:
      Self-reports from cross-sectional Internet and mail surveys. Comparisons of: (a)
      766 daily users of nicotine-containing e-cigarettes with 30 daily users of
      nicotine-free e-cigarettes; (b) 911 former smokers who used the e-cigarette daily
      with 451 former smokers who used the nicotine gum daily (but no e-cigarette); (c)
      125 daily e-cigarette users who smoked daily (dual users) with two samples of
      daily smokers who did not use e-cigarettes (2206 enrolled on the Internet and 292
      enrolled by mail from the general population of Geneva). We used the Fagerstrom
      test for nicotine dependence, the nicotine dependence syndrome scale, the
      cigarette dependence scale and versions of these scales adapted for e-cigarettes
      and nicotine gums. RESULTS: Dependence ratings were slightly higher in users of
      nicotine-containing e-cigarettes than in users of nicotine-free e-cigarettes. In
      former smokers, long-term (>3 months) users of e-cigarettes were less dependent
      on e-cigarettes than long-term users of the nicotine gum were dependent on the
      gum. There were few differences in dependence ratings between short-term (<=3
      months) users of gums or e-cigarettes. Dependence on e-cigarettes was generally
      lower in dual users than dependence on tobacco cigarettes in the two other
      samples of daily smokers. CONCLUSIONS: Some e-cigarette users were dependent on
      nicotine-containing e-cigarettes, but these products were less addictive than
      tobacco cigarettes. E-cigarettes may be as or less addictive than nicotine gums,
      which themselves are not very addictive.

PMID- 25561386
TI  - Cognitive manifestations of drinking-smoking associations: preliminary findings
      with a cross-primed Stroop task.
AB  - BACKGROUND: Despite tremendous growth in research examining the role of cognitive
      bias in addictive behaviors, scant consideration has been paid to the close
      association between smoking and drinking behavior. This study sought to determine
      whether an association between smoking and drinking could be observed at an
      implicit level using a novel cognitive bias task, as well as characterize the
      relationship between performance on this task and clinically relevant variables
      (i.e., heaviness of use/dependence). METHODS: Individuals (N=51) with a range of
      smoking and drinking patterns completed a modified Stroop task in which
      participants identified the color of drinking, smoking and neutral words that
      were each preceded by drinking, smoking or neutral picture primes. Participants
      also provided information regarding the heaviness of their smoking and drinking
      behavior and completed self-report measures of alcohol and nicotine dependence.
      RESULTS: Response times to smoking and drinking words were significantly slowed
      following the presentation of either smoking or drinking picture primes. This
      effect did not differ across subgroups. However, the strength of the coupling
      between smoking and drinking prime effects was greater among heavier drinkers,
      who also exhibited a concordant looser coupling of the effects of smoking and
      drinking primes on smoking words. CONCLUSIONS: Associations between smoking and
      drinking can be observed at an implicit level and may be strongest for heavier
      drinkers.

PMID- 25561388
TI  - The impact of anticipated and unanticipated smoking opportunities on cigarette
      smoking and nicotine lozenge responses.
AB  - BACKGROUND: Perceptions regarding the availability of smoking opportunities are
      known to affect cigarette craving; however, whether they impact actual smoking or
      how smokers respond to acute nicotine replacement therapy (NRT) administration is
      not known. This study examined the impact of pharmacological and expectancy
      components of NRT administration on craving and smoking in smokers anticipating
      or not anticipating an imminent smoking opportunity. METHODS: In total, 154
      smokers (84 male) completed an experimental session in which instructions
      regarding the nicotine content of a lozenge (4 mg vs. no nicotine) and regarding
      the availability of a future smoking opportunity were manipulated. Cigarette
      craving was assessed before and after manipulations and lozenge administration.
      All participants were then allotted 1h to self-administer as many cigarette puffs
      as they wished. RESULTS: Unanticipated smoking opportunities reduced latency to
      self-administration (p<0.001), regardless of nicotine expectancy or pharmacology.
      When analyses included all participants, nicotine reduced intentions to smoke
      (p=0.016) and withdrawal-related craving (p=0.043) regardless of expectancy.
      Conversely, analyses using only "believers" of the nicotine content instructions
      revealed that nicotine expectancy reduced intentions to smoke (p=0.034) and
      withdrawal-related craving (p=0.047) regardless of actual nicotine
      administration. "Believers" also reported increased withdrawal-related craving
      when a smoking opportunity was perceived to be imminent (p=0.041). These effects
      were not significant when analyses included all participants. CONCLUSIONS:
      Findings suggest that unexpected smoking opportunities may be more appealing than
      expected ones regardless of perceived or actual acute NRT use. They also
      highlight the importance of reporting balanced placebo findings using all
      participants as well as "believers" only.

PMID- 25561387
TI  - Animal models to assess the abuse liability of tobacco products: effects of
      smokeless tobacco extracts on intracranial self-stimulation.
AB  - BACKGROUND: Preclinical models are needed to inform regulation of tobacco
      products by the Food and Drug Administration (FDA). Typically, animal models of
      tobacco addiction involve exposure to nicotine alone or nicotine combined with
      isolated tobacco constituents (e.g. minor alkaloids). The goal of this study was
      to develop a model using extracts derived from tobacco products that contain a
      range of tobacco constituents to more closely model product exposure in humans.
      METHODS: This study compared the addiction-related effects of nicotine alone and
      nicotine dose-equivalent concentrations of aqueous smokeless tobacco extracts on
      intracranial self-stimulation (ICSS) in rats. Extracts were prepared from Kodiak
      Wintergreen, a conventional product, or Camel Snus, a potential "modified risk
      tobacco product". Binding affinities of nicotine alone and extracts at various
      nicotinic acetylcholine receptor (nAChR) subtypes were also compared. RESULTS:
      Kodiak and Camel Snus extracts contained levels of minor alkaloids within the
      range of those shown to enhance nicotine's behavioral effects when studied in
      isolation. Nonetheless, acute injection of both extracts produced reinforcement
      enhancing (ICSS threshold-decreasing) effects similar to those of nicotine alone
      at low to moderate nicotine doses, as well as similar reinforcement
      attenuating/aversive (ICSS threshold-increasing) effects at high nicotine doses.
      Extracts and nicotine alone also had similar binding affinity at all nAChRs
      studied. CONCLUSIONS: Relative nicotine content is the primary pharmacological
      determinant of the abuse liability of Kodiak and Camel Snus as measured using
      ICSS. These models may be useful to compare the relative abuse liability of other
      tobacco products and to model FDA-mandated changes in product performance
      standards.

PMID- 25561389
TI  - Does watching a video on third molar surgery increase patients' anxiety level?
AB  - OBJECTIVE: To identify the effects of watching live taping of third molar removal
      on patients' anxiety levels before and after extraction. STUDY DESIGN: This study
      was based on a prospective, cross-sectional, observational investigation of the
      different patient education techniques about the effect of third molar removal on
      patients' anxiety level. A total of 333 patients were randomized into three
      groups: two study groups (for group 1, basic information was given verbally; for
      group 2, which was the study group, basic information was given verbally and
      through a movie on third molar extraction); and a control group (basic
      information was given verbally; it did not include information on operative
      procedures and recovery). Anxiety levels were assessed by using the Dental
      Anxiety Scale (DAS) and the Spielberger State-Trait Anxiety Inventory (STAI).
      Pain was assessed with a visual analog scale. Statistical analysis was performed
      with SPSS 16.0. RESULTS: Group 2 patients were significantly more anxious before
      the surgical procedure, and the most significant decreases in DAS and STAI scores
      were observed in that group. The age, surgery time, and education level were not
      correlated with anxiety or pain levels; however, female patients had high levels
      of anxiety (P < .05). CONCLUSION: Preoperative multimedia information increases
      the anxiety of patients undergoing third molar surgery.

PMID- 25561390
TI  - Sebaceous carcinoma of the maxillary gingival: First reported case involving the
      gingiva.
AB  - Sebaceous carcinoma of the oral cavity is extremely rare. To date, only 9 cases
      of primary sebaceous carcinoma involving the oral cavity have been reported in
      the English literature, with the majority of cases occurring on the buccal
      mucosa. This report describes a case of sebaceous carcinoma involving the
      maxillary gingiva. To our knowledge this is the first reported case of sebaceous
      carcinoma of the gingiva. 

PMID- 25561391
TI  - Incentivizing "structures" over "outcomes" to bridge the knowing-doing gap.

PMID- 25561392
TI  - Cinnamaldehyde and nitric oxide attenuate advanced glycation end products-induced
      the Jak/STAT signaling in human renal tubular cells.
AB  - Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of
      Cinnamomum osmophloeum kaneh. It possesses anti-diabetic properties in vitro and
      in vivo and has anti-inflammatory and anti-cancer effects. To explore whether
      cinnamaldehyde was linked to altered advanced glycation end products (AGE)
      mediated diabetic nephropathy, the molecular mechanisms of cinnamaldehyde
      responsible for inhibition of AGE-reduced nitric oxide (NO) bioactivity in human
      renal proximal tubular cells were examined. We found that raising the ambient AGE
      concentration causes a dose-dependent decrease in NO generation. Cinnamaldehyde
      significantly reverses AGE-inhibited NO generation and induces high levels of
      cGMP synthesis and PKG activation. Treatments with cinnamaldehyde, the NO donor S
      nitroso-N-acetylpenicillamine, and the JAK2 inhibitor AG490 markedly attenuated
      AGE-inhibited NOS protein levels and NO generation. Moreover, AGE-induced the
      JAK2-STAT1/STAT3 activation, RAGE/p27(Kip1) /collagen IV protein levels, and
      cellular hypertrophy were reversed by cinnamaldehyde. The ability of
      cinnamaldehyde to suppress STAT activation was also verified by the observation
      that it significantly increased SCOS-3 protein level. These findings indicate for
      the first time that in the presence of cinnamaldehyde, the suppression of AGE
      induced biological responses is probably mediated by inactivating the JAK2
      STAT1/STAT3 cascade or activating the NO pathway.

PMID- 25561394
TI  - Elemental mapping inventory of the fish Liza aurata brain: a biomarker of metal
      pollution vulnerability.
AB  - The elemental distributions in optic tectum of brains of wild Liza aurata a
      teleost fish captured in polluted and reference coastal areas were assessed
      quantitatively by nuclear microscopy providing insights into brain vulnerability
      to metal pollution. Elemental maps enabled us to visualize optic tectum layers
      and identify cellular arrangements. Whereas Cl, K and Ca contents identify
      meninges, the Ca, Fe and Zn concentrations distinguish the underneath grey
      matter, white matter and inner cellular layers. Exposed animals showed
      significantly decreased P concentrations and increased contents of Cu, Zn and Ni
      in all brain structures. These changes highlight homeostasis modification,
      altered permeability of the blood-brain barrier and suggest risk for neurological
      toxicity. Our study initiated for the first time an inventory of physiological
      measures containing images and elemental compositions of brain regions of fish
      exposed to different environmental conditions. This will help defining total and
      local brain vulnerability to metals and pollution levels. 

PMID- 25561393
TI  - Ribosome nascent chain complexes of the chloroplast-encoded cytochrome b6
      thylakoid membrane protein interact with cpSRP54 but not with cpSecY.
AB  - We analysed the interplay between the cpSecY, cpSRP54 and the chloroplast-encoded
      cytochrome b6 via isolation of chloroplast ribosome nascent chain complexes and
      the use of cross-linking factors, antibodies and mass spectroscopy analyses. We
      showed that the cytochrome b6 nascent polypeptide complex is tightly associated
      with ribosomes and that the translation of cytochrome b6 was discontinuous. The
      causes of ribosome pausing and the functional significance of this phenomenon may
      be related to proper protein folding, insertion into thylakoid membranes and the
      association of cofactors during this process. It was also found that cpSecY was
      not in the vicinity of cytochrome b6 intermediates during the elongation process
      and does not act with mature cytochrome b6 after translation. Using the approach
      of cross-linking during elongation of the cytochrome b6 protein, we showed that
      cpSRP54 interacts strongly with the elongating nascent chain. 

PMID- 25561396
TI  - Evaluation of different classification methods for the diagnosis of schizophrenia
      based on functional near-infrared spectroscopy.
AB  - BACKGROUND: Based on near-infrared spectroscopy (NIRS), recent converging
      evidence has been observed that patients with schizophrenia exhibit abnormal
      functional activities in the prefrontal cortex during a verbal fluency task
      (VFT). Therefore, some studies have attempted to employ NIRS measurements to
      differentiate schizophrenia patients from healthy controls with different
      classification methods. However, no systematic evaluation was conducted to
      compare their respective classification performances on the same study
      population. NEW METHOD: In this study, we evaluated the classification
      performance of four classification methods (including linear discriminant
      analysis, k-nearest neighbors, Gaussian process classifier, and support vector
      machines) on an NIRS-aided schizophrenia diagnosis. We recruited a large sample
      of 120 schizophrenia patients and 120 healthy controls and measured the
      hemoglobin response in the prefrontal cortex during the VFT using a multichannel
      NIRS system. Features for classification were extracted from three types of NIRS
      data in each channel. We subsequently performed a principal component analysis
      (PCA) for feature selection prior to comparison of the different classification
      methods. RESULTS: We achieved a maximum accuracy of 85.83% and an overall mean
      accuracy of 83.37% using a PCA-based feature selection on oxygenated hemoglobin
      signals and support vector machine classifier. COMPARISON WITH EXISTING METHODS:
      This is the first comprehensive evaluation of different classification methods
      for the diagnosis of schizophrenia based on different types of NIRS signals.
      CONCLUSIONS: Our results suggested that, using the appropriate classification
      method, NIRS has the potential capacity to be an effective objective biomarker
      for the diagnosis of schizophrenia.

PMID- 25561397
TI  - Towards an optimal paradigm for simultaneously recording cortical and brainstem
      auditory evoked potentials.
AB  - BACKGROUND: Simultaneous recording of brainstem and cortical event-related brain
      potentials (ERPs) may offer a valuable tool for understanding the early neural
      transcription of behaviorally relevant sounds and the hierarchy of signal
      processing operating at multiple levels of the auditory system. To date, dual
      recordings have been challenged by technological and physiological limitations
      including different optimal parameters necessary to elicit each class of ERP
      (e.g., differential adaptation/habitation effects and number of trials to obtain
      adequate response signal-to-noise ratio). NEW METHOD: We investigated a new
      stimulus paradigm for concurrent recording of the auditory brainstem frequency
      following response (FFR) and cortical ERPs. The paradigm is "optimal" in that it
      uses a clustered stimulus presentation and variable interstimulus interval (ISI)
      to (i) achieve the most ideal acquisition parameters for eliciting subcortical
      and cortical responses, (ii) obtain an adequate number of trials to detect each
      class of response, and (iii) minimize neural adaptation/habituation effects.
      RESULTS AND COMPARISON WITH EXISTING METHOD: Comparison between clustered and
      traditional (fixed, slow ISI) stimulus paradigms revealed minimal change in
      amplitude or latencies of either the brainstem FFR or cortical ERP. The clustered
      paradigm offered over a 3* increase in recording efficiency compared to
      conventional (fixed ISI presentation) and thus, a more rapid protocol for
      obtaining dual brainstem-cortical recordings in individual listeners.
      CONCLUSIONS: We infer that faster recording of subcortical and cortical
      potentials might allow more complete and sensitive testing of neurophysiological
      function and aid in the differential assessment of auditory function.

PMID- 25561398
TI  - Engineered Si sandwich electrode: Si nanoparticles/graphite sheet hybrid on ni
      foam for next-generation high-performance lithium-ion batteries.
AB  - Si-based electrodes for lithium ion batteries typically exhibit high specific
      capacity but poor cycling performance. A possible strategy to improve the cycling
      performance is to design a novel electrode nanostructure. Here we report the
      design and fabrication of Ni/Si-nanoparticles/graphite clothing hybrid electrodes
      with a sandwich structure. An efficient dip-coating of Si-NPs combined with
      carbon deposition was adopted to synthesize the unique architecture, where the Si
      NPs are sandwiched between the Ni matrix and the graphite clothing. This material
      architecture offers many critical features that are desirable for high
      performance Si-based electrodes, including efficient ion diffusion, high
      conductivity, and structure durability, thus ensuring the electrode with
      outstanding electrochemical performance (reversible capacity of 1800 mA h g(-1)
      at 2 A g(-1) after 500 cycles). In addition, the hybrid anode does not require
      any polymeric binder and conductive additives and holds great potential for
      application in Li-ion batteries. 

PMID- 25561395
TI  - Co-registration of magnetic resonance spectroscopy and transcranial magnetic
      stimulation.
AB  - Transcranial magnetic stimulation (TMS) is a widely used tool for noninvasive
      modulation of brain activity, that is thought to interact primarily with
      excitatory and inhibitory neurotransmitter systems. Neurotransmitters such as
      glutamate and GABA can be measured by magnetic resonance spectroscopy (MRS). An
      important prerequisite for studying the relationship between MRS neurotransmitter
      levels and responses to TMS is that both modalities should examine the same
      regions of brain tissue. However, co-registration of TMS and MRS has been little
      studied to date. This study reports on a procedure for the co-registration and co
      visualization of MRS and TMS, successfully localizing the hand motor cortex, as
      subsequently determined by its functional identification using TMS. Sixteen
      healthy subjects took part in the study; in 14 of 16 subjects, the TMS determined
      location of motor activity intersected the (2.5cm)(3) voxel selected for MRS,
      centered on the so called 'hand knob' of the precentral gyrus. It is concluded
      that MRS voxels placed according to established anatomical landmarks in most
      cases agree well with functional determination of the motor cortex by TMS.
      Reasons for discrepancies are discussed. 

PMID- 25561399
TI  - Oestrogen receptor alpha expression in neovaginal tissue of women following
      modified Abbe-McIndoe technique and in premenopausal women.
AB  - The aim of the study was to compare the expression of oestrogen receptor alpha
      (ERalpha) in neovaginal tissue of patients with vaginal agenesis following
      neovaginoplasty using regenerated, oxidised cellulose in premenopausal women. A
      prospective, observational case-control study was performed on eight patients
      with vaginal agenesis following modified Abbe-McIndoe neovaginoplasty and 10
      control premenopausal women following benign gynaecologic surgery. 6F11
      monoclonal antibody was used to determine ERalpha expression in the vaginal
      mucosa. Quantitative and qualitative evaluations were performed, respectively, in
      vaginal epithelium and stroma. The thickness of the vaginal epithelium was
      determined as the vertical distance between the basal layer cells and the apical
      surface of the superficial layer. The percentage of ERalpha-expressing cells was
      higher in the control group, except in the superficial zone of the epithelium. In
      the stromal tissue, ERalpha was detected in only one patient from the neovagina
      group compared with nine women in the control group. The neovagina group had a
      statistically thinner epithelium. Our study suggests that women with vaginal
      agenesis following modified Abbe-McIndoe neovaginoplasty using regenerated
      oxidised, cellulose experience relatively local hypo-oestrogenism in the first
      year after surgery, with repercussion in vaginal trophism. 

PMID- 25561400
TI  - Functional characterization of two acyltransferases from Populus trichocarpa
      capable of synthesizing benzyl benzoate and salicyl benzoate, potential
      intermediates in salicinoid phenolic glycoside biosynthesis.
AB  - Salicinoids are phenolic glycosides (PGs) characteristic of the Salicaceae and
      are known defenses against insect herbivory. Common examples are salicin,
      salicortin, tremuloidin, and tremulacin, which accumulate to high concentrations
      in the leaves and bark of willows and poplars. Although their biosynthetic
      pathway is not known, recent work has suggested that benzyl benzoate may be a
      potential biosynthetic intermediate. Two candidate genes, named PtACT47 and
      PtACT49, encoding BAHD-type acyl transferases were identified and are predicted
      to produce such benzylated secondary metabolites. Herein described are the cDNA
      cloning, heterologous expression and in vitro functional characterization of
      these two BAHD acyltransferases. Recombinant PtACT47 exhibited low substrate
      selectivity and could utilize acetyl-CoA, benzoyl-CoA, and cinnamoyl-CoA as acyl
      donors with a variety of alcohols as acyl acceptors. This enzyme showed the
      greatest Km/Kcat ratio (45.8 nM(-1) s(-1)) and lowest Km values (45.1 MUM) with
      benzoyl-CoA and salicyl alcohol, and was named benzoyl-CoA: salicyl alcohol O
      benzoyltransferase (PtSABT). Recombinant PtACT49 utilized a narrower range of
      substrates, including benzoyl-CoA and acetyl-CoA and a limited number of
      alcohols. Its highest Km/Kcat (31.8 nM(-1) s(-1)) and lowest Km (55.3 MUM) were
      observed for benzoyl-CoA and benzyl alcohol, and it was named benzoyl-CoA: benzyl
      alcohol O-benzoyltransferase (PtBEBT). Both enzymes were also capable of
      synthesizing plant volatile alcohol esters, such as hexenyl benzoate, at trace
      levels. Although the activities demonstrated are consistent with roles in
      salicinoid biosynthesis, direct tests of this hypothesis using transgenic poplar
      must still be performed.

PMID- 25561401
TI  - Metabolic profiling of Commiphora wightii (guggul) reveals a potential source for
      pharmaceuticals and nutraceuticals.
AB  - Guggul gum resin from Commiphora wightii (syn. Commiphoramukul) has been used for
      centuries in Ayurveda to treat a variety of ailments. The NMR and GC-MS based non
      targeted metabolite profiling identified 118 chemically diverse metabolites
      including amino acids, fatty acids, organic acids, phenolic acids, pregnane
      derivatives, steroids, sterols, sugars, sugar alcohol, terpenoids, and tocopherol
      from aqueous and non-aqueous extracts of leaves, stem, roots, latex and fruits of
      C. wightii. Out of 118, 51 structurally diverse aqueous metabolites were
      characterized by NMR spectroscopy. For the first time quinic acid and myo
      inositol were identified as the major metabolites in C. wightii. Very high
      concentration of quinic acid was found in fruits (553.5 +/- 39.38 mg g(-1) dry
      wt.) and leaves (212.9 +/- 10.37 mg g(-1) dry wt.). Similarly, high concentration
      of myo-inositol (168.8 +/- 13.84 mg g(-1) dry wt.) was observed from fruits. The
      other metabolites of cosmeceutical, medicinal, nutraceutical and industrial
      significance such as alpha-tocopherol, n-methylpyrrolidone (NMP), trans-farnesol,
      prostaglandin F2, protocatechuic, gallic and cinnamic acids were identified from
      non-aqueous extracts using GC-MS. These important metabolites have thus far not
      been reported from this plant. Isolation of a fungal endophyte, (Nigrospora sps.)
      from this plant is the first report. The fungal endophyte produced a substantial
      quantity of bostrycin and deoxybostrycin known for their antitumor properties.
      Very high concentrations of quinic acid and myo-inositol in leaves and fruits; a
      substantial quantity of alpha-tocopherol and NMP in leaves, trans-farnesol in
      fruits, bostrycin and deoxybostrycin from its endophyte makes the taxa distinct,
      since these metabolites with medicinal properties find immense applications as
      dietary supplements and nutraceuticals.

PMID- 25561402
TI  - Career building as a neuroscientist at a research hospital.

PMID- 25561403
TI  - Tertiary nitrification using moving-bed biofilm reactor: a case study in Tunisia.
AB  - In this study, the effect of operational conditions on biofilm development and
      nitrification in moving-bed biofilm reactor (MBBR) was investigated. The reactor
      was operated in a continuously fed regime during 170 days and with theoretical
      hydraulic retention time of 7 h, respectively. The presence of chemical oxygen
      demand (COD) increased the time required to form stable nitrifying. Subsequent
      stepwise increase of influent COD caused an increment in total polysaccharide
      (PS) and protein (PN) content, which was accompanied by an attachment of the
      biofilm, as shown by atomic force microscope (AFM). PS and PN concentrations
      proved to be good indicators of biomass development and attachment in MBBR
      system. Reactor was operated and water quality was characterized before and after
      treatment. Parameters including pH, 5-day biochemical oxygen demand (BOD5), total
      suspended solids (TSS) (COD), PN, PS, and fecal bacteria in both raw and treated
      wastewater were monitored during the treatment. The removal rates of ammonium
      nitrogen (NH4 (+)-N), BOD5, COD, and TSS are 95, 67.5, 69.2, and 73.33 %,
      respectively. The average bacterial reduction between the inlet and the outlet
      was of the order of 5 +/- 1 logarithmic units for fecal coliforms. AFM showed
      that distinct biofilm and extracellular polymeric substances were formed in
      biofilm was thicker in the 70 days than in the 30 days. These results showed that
      the consumption rate for each substrate increased parabolically with biofilm
      thickness due to the increased amount of biomass Thus, MBBR can serve as a
      promising technology for wastewater treatment and can be scaled up for small
      communities in the developing countries. 

PMID- 25561404
TI  - Induction of osmoadaptive mechanisms and modulation of cellular physiology help
      Bacillus licheniformis strain SSA 61 adapt to salt stress.
AB  - Bacillus licheniformis strain SSA 61, originally isolated from Sambhar salt lake,
      was observed to grow even in the presence of 25 % salt stress. Osmoadaptive
      mechanisms of this halotolerant B. licheniformis strain SSA 61, for long-term
      survival and growth under salt stress, were determined. Proline was the
      preferentially accumulated compatible osmolyte. There was also increased
      accumulation of antioxidants ascorbic acid and glutathione. Among the different
      antioxidative enzymes assayed, superoxide dismutase played the most crucial role
      in defense against salt-induced stress in the organism. Adaptation to stress by
      the organism involved modulation of cellular physiology at various levels. There
      was enhanced expression of known proteins playing essential roles in stress
      adaptation, such as chaperones DnaK and GroEL, and general stress protein YfkM
      and polynucleotide phosphorylase/polyadenylase. Proteins involved in amino acid
      biosynthetic pathway, ribosome structure, and peptide elongation were also
      overexpressed. Salt stress-induced modulation of expression of enzymes involved
      in carbon metabolism was observed. There was up-regulation of a number of enzymes
      involved in generation of NADH and NADPH, indicating increased cellular demand
      for both energy and reducing power. 

PMID- 25561405
TI  - Oxidative damage induced by heat stress could be relieved by nitric oxide in
      Trichoderma harzianum LTR-2.
AB  - Trichoderma harzianum is an important commercial biocontrol fungal agent. The
      temperature has been shown to be an important parameter and strain-specific to
      the mycelia growth of fungi, but less report makes the known of the mechanisms in
      T. harzianum. In our study, a 6-h treatment of heat increased the thiobarbituric
      acid reactive substances (TBARS) and nitric oxide (NO) concentration in mycelia
      to 212 and 230 % the level of the control, respectively. The exogenous NO donor
      sodium nitroprusside (150 MUM) reduced the TBARS concentration to 53 % of that
      under heat stress (HS). At the same time, the NO-specific scavenger at 250 MUM, 2
      (4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-1-oxyl-3-oxide, prevented the
      exogenous NO-relieved TBARS accumulation under HS. The increased NO concentration
      under HS was reduced 41 % by the NO synthase (NOS) inhibitor L-N(G)-nitroarginine
      methyl ester, but not the nitrate reductase (NR) inhibitor tungstate. Our study
      exhibited that NO can protect the mycelia of T. harzianum from HS and reduce the
      oxidative damage by enhancing the activity of NOS and NR. 

PMID- 25561406
TI  - Determination of the proteins encoded by BmBDV VD1-ORF4 and their interacting
      proteins in BmBDV-infected midguts.
AB  - Bombyx mori bidensovirus (BmBDV) VD1-ORF4 consists of 3,318 nucleotides, which
      codes for a predicted protein with molecular weight of about 127 kDa. However,
      the authentic proteins encoded by VD1-ORF4 in silkworm midguts infected with
      BmBDV and their interacting proteins are still unclear. In this study, Western
      blot analysis revealed that a 127-kDa protein was confirmed to be translated from
      the VD1-ORF4 transcript using polyclonal antibodies and monoclonal antibodies
      against VD1-ORF4 deduced amino acid. Moreover, four smaller proteins with
      molecular weight of about 70, 60, 53, and 42 kDa were also examined in the
      infected midguts. Transient expression assay indicated that the expression amount
      of VD1-ORF4 fused with egfp was at least 30-fold lower than that of egfp gene,
      and immunofluorescence staining result indicated that these proteins encoded by
      VD1-ORF4 were located in both the cytoplasm and nucleus. Co-immunoprecipitation
      result showed that Aminopeptidase and Heat shock protein 90 can be captured by
      these proteins encoded by VD1-ORF4. In conclusion, multiple proteins were
      produced from the transcripts of VD1-ORF4 gene by an uncertain expression
      strategy, which may play important roles in viral replication and assembly. 

PMID- 25561407
TI  - Effects of fibrinopurulent polyserositis in broilers on post-harvest
      microbiological parameters relevant to public health of broiler meat.
AB  - Fibrinopurulent polyserositis is of utmost importance in commercial broiler
      production worldwide. This multifactorial endemic disease is marked by severe
      clinical alterations post-mortem, yet its effects on food safety and processing
      hygiene criteria remain unclear. Current considerations presume that bacteraemia
      lead to meat being unfit for consumption. In the present study, we evaluated some
      microbiological criteria of affected broiler carcasses in comparison to
      unaffected control broiler carcasses. The results thereof indicated that the
      lesions did not result in higher bacterial counts or in an increased percentage
      of contaminated meat. The carry-over of associated zoonotic pathogens into the
      food chain seems to be not more prevalent in birds affected with non-systemic
      affections of polyserositis. 

PMID- 25561408
TI  - Increases in PKC gamma expression in trigeminal spinal nucleus is associated with
      orofacial thermal hyperalgesia in streptozotocin-induced diabetic mice.
AB  - Painful diabetic polyneuropathy (PDN) at the early phrase of diabetes frequently
      exhibits increased responsiveness to nociception. In diabetic patients and animal
      models, alterations in the transmission of orofacial sensory information have
      been demonstrated in trigeminal system. Herein, we examined the changes of
      protein kinase Cgamma subunit (PKCgamma) in trigeminal spinal nucleus (Sp5C) and
      observed the development of orofacial thermal sensitivity in streptozotocin (STZ)
      induced type 1 diabetic mice. With hyperglycemia and body weight loss, STZ mice
      exhibited orofacial thermal hyperalgesia, along with increased PKCgamma
      expression in Sp5C. Insulin treatment at the early stage of diabetes could
      alleviate the orofacial thermal hyperalgesia and impaired increased PKCgamma in
      Sp5C in diabetic mice. In summary, our results demonstrate that PKCgamma might be
      involved in orofacial thermal hyperalgesia of diabetes, and early insulin
      treatment might be effective way to treat orofacial PDN. 

PMID- 25561409
TI  - Adhesion prevention agents for gynaecological surgery: an overview of Cochrane
      reviews.
AB  - BACKGROUND: Intraperitoneal adhesions are associated with considerable co
      morbidity and have large financial and public health repercussions. They have
      secondary effects that include chronic pelvic pain, dyspareunia, subfertility and
      bowel obstruction. In women with adhesions, subsequent surgery is more difficult,
      often takes longer, and is associated with a higher complication rate (Broek
      2013). The significant burden of adhesions has led to the development of several
      anti-adhesion agents, although there is disagreement as to their relative
      effectiveness. OBJECTIVES: To summarise evidence derived from Cochrane systematic
      reviews on the clinical safety and effectiveness of solid agents, gel agents,
      liquid agents and pharmacological agents, used as adjuvants to prevent formation
      of adhesions after gynaecological pelvic surgery. METHODS: The Cochrane Database
      of Systematic Reviews was searched using the keyword 'adhesion' up to August
      2014. The Cochrane information management system was also searched for any titles
      or protocols of reviews in progress. Two review authors independently extracted
      information from the reviews, with disagreements being resolved by a third review
      author. The quality of the included reviews was described in a narrative manner,
      and the AMSTAR tool was used to formally assess each review included in this
      overview. The quality of evidence provided in the original reviews was described
      using GRADE methods. MAIN RESULTS: We included two reviews, one with 18 studies
      comparing solid agents (oxidised regenerated cellulose expanded
      polytetrafluoroethylene, sodium hyaluronate and carboxymethylcellulose, and
      fibrin sheets) with control or with each other. The other review included 29
      studies which compared liquid agents (4% icodextrin, 32% dextran, crystalloids),
      gel agents (carboxymethylcellulose and polyethylene oxide, polyethylene glycol
      gels, hyaluronic acid based gel, 0.5% ferric hyaluronate gel, sodium hyaluronate
      spray) and pharmacological agents (gonadotrophin-releasing hormone agonist,
      reteplase plasminogen activator, N,O-carboxymethyl chitosan, steroid agents,
      intraperitoneal noxytioline, intraperitoneal heparin, systemic promethazine) with
      control or each other. Both reviews met all of the criteria of the AMSTAR
      assessment.The reviews included as outcomes both the primary outcomes of this
      overview (pelvic pain, pregnancy, live birth rate and quality of life (QoL)) and
      our secondary outcomes (adverse effects, presence or absence of adhesions at
      second-look laparoscopy (SLL) and adhesion score). However, neither of the
      reviews identified any primary studies of solid, gel or pharmacological agents
      that reported any of our primary outcomes. The only studies in either review that
      reported any of our primary outcomes were studies comparing liquid agents versus
      control (saline or Hartmann's solution), which reported pelvic pain (two
      studies), live birth (two studies) and pregnancy (three studies).An external
      source of funding was stated for 25 of the 47 studies across both reviews; in 24
      of these studies the funding was commercial. Solid agents (18 studies)None of our
      primary outcomes were reported. Adverse events were reported as an outcome by
      only 9 of the 18 studies. These reported no adverse events. Liquid agents (nine
      studies)There was no evidence of a difference between liquid agents and control
      (saline or Hartmann's solution) with respect to pelvic pain (odds ratio (OR)
      0.65, 95% confidence interval (CI) 0.37 to 1.14, 1 study, n = 286, moderate
      quality evidence), pregnancy rate (OR 0.64, 95% CI 0.36 to 1.14, 3 studies, n =
      310, moderate quality evidence) or live birth rate (OR 0.67, 95% CI 0.29 to 1.58,
      2 studies, n = 208, moderate quality evidence). No studies of liquid agents
      reported QoL. Adverse events were not reported as an outcome by any of the nine
      studies. Gel agents (seven studies)None of our primary outcomes were reported.
      Adverse events were not reported as an outcome by any of the seven studies.
      Pharmacological agents (seven studies)None of our primary outcomes were reported.
      Adverse events were reported as an outcome by only one of the seven primary
      studies. This study reported no evidence of difference in ectopic pregnancy rates
      between intraperitoneal noxytioline and no treatment (OR 4.91, 95% CI 0.45 to
      53.27, 1 study, n = 33, low quality evidence). AUTHORS' CONCLUSIONS: There is
      insufficient evidence to allow us to draw any conclusions about the effectiveness
      and safety of anti-adhesion agents in gynaecological surgery, due to the lack of
      data on pelvic pain, fertility outcomes, quality of life or safety. A substantial
      proportion of research in this field has been funded by private companies that
      manufacture these agents, and further high powered, independent trials will be
      needed before definitive conclusions can be made.

PMID- 25561410
TI  - Platelet-derived MIF: a novel platelet chemokine with distinct recruitment
      properties.
AB  - OBJECTIVE: Macrophage migration inhibitory factor (MIF) is an inflammatory
      cytokine with chemokine-like functions that plays a role in several inflammatory
      diseases including atherosclerosis. We recently demonstrated that in addition to
      macrophages and endothelial cells, platelets are a source of MIF. However, the
      functional relevance of platelet-derived MIF and differences to other platelet
      chemokines are unclear. Here, we sought to define the secretion pattern of
      platelet MIF and to characterize its functional profile in comparison with known
      atherogenic platelet chemokines. METHODS AND RESULTS: Applying ELISA, we show
      that MIF is released from thrombin-stimulated platelets after 2 h, whereas CXCL12
      and CXCL4 are secreted within minutes. Applied to platelets, MIF, unlike CXCL12,
      did not enhance platelet activation as analyzed by platelet aggregation, CD62P
      exposure and chemokine secretion studies. In contrast, both MIF and CXCL12
      attenuated ADP-induced calcium transients in platelets. Transmigration and
      monocyte flow adhesion assays toward conditioned platelet supernatants together
      with MIF antibody blockade or supernatants from Mif(-/-) mice suggested that
      platelet-derived MIF has a stronger chemotactic activity than CXCL12 at its
      respective optimal secretion interval, and showed that platelet MIF substantially
      contributes to monocyte adhesion on endothelial layers. Moreover, MIF was found
      to delay clot retraction. CONCLUSIONS: We demonstrate that MIF differs from other
      platelet-derived chemokines by delayed secretion kinetics and by a distinct
      autocrine/paracrine modulation potential. Importantly, MIF was found to be a
      major platelet-derived chemotactic recruitment factor with clot-modulating
      properties and therefore might be relevant in inflammatory diseases such as
      atherosclerosis.

PMID- 25561411
TI  - Technical decision making with higher order structure data: utilization of
      differential scanning calorimetry to elucidate critical protein structural
      changes resulting from oxidation.
AB  - Differential scanning calorimetry (DSC) is a useful tool for monitoring thermal
      stability of the molecular conformation of proteins. Here, we present an example
      of the sensitivity of DSC to changes in stability arising from a common chemical
      degradation pathway, oxidation. This Note is part of a series of industry case
      studies demonstrating the application of higher order structure data for
      technical decision making. For this study, six protein products from three
      structural classes were evaluated at multiple levels of oxidation. For each
      protein, the melting temperature (Tm ) decreased linearly as a function of
      oxidation; however, differences in the rate of change in Tm , as well as
      differences in domain Tm stability were observed across and within structural
      classes. For one protein, analysis of the impact of oxidation on protein function
      was also performed. For this protein, DSC was shown to be a leading indicator of
      decreased antigen binding suggesting a subtle conformation change may be underway
      that can be detected using DSC prior to any observable impact on product potency.
      Detectable changes in oxidized methionine by mass spectrometry (MS) occurred at
      oxidation levels below those with a detectable conformational or functional
      impact. Therefore, by using MS, DSC, and relative potency methods in concert, the
      intricate relationship between a primary structural modification, changes in
      conformational stability, and functional impact can be elucidated.

PMID- 25561412
TI  - Total synthesis of gobiusxanthin stereoisomers and their application to
      determination of absolute configurations of natural products: revision of
      reported absolute configuration of epigobiusxanthin.
AB  - (3R)-Gobiusxanthin stereoisomers (1a-d) were synthesized by stereoselective
      Wittig reaction of the (3R)-C15-acetylenic tri-n-butylphosphonium salt 7 with C25
      apocarotenal stereoisomers 5a,b and 14a,b bearing four kinds of 3,6-dihydroxy
      epsilon-end groups. The validity of the reported stereochemistry of gobiusxanthin
      was demonstrated by the fact that the reported spectral data of natural
      gobiusxanthin were in agreement with those of synthetic (3R,3'S,6'R)
      gobiusxanthin (1a). On the other hand, the reported CD spectral data of natural
      epigobiusxanthin, which has been assigned as (3R,3'R,6'R)-isomer (3'
      epigobiusxanthin), were identical with those of synthetic (3R,3'S,6'S)-isomer 1d
      (6'-epigobiusxanthin) rather than those of the corresponding synthetic 3'-epi
      isomer 1b. It was found that the stereochemistry at C3-position has little effect
      on the shape of their CD spectra. Thus, in order to reinforce the validity of the
      absolute configurations at C3-position of natural specimens, (3S,3'S,6'R)- and
      (3S,3'S,6'S)-stereoisomers 1e and 1f were also synthesized and a HPLC analytical
      method for four stereoisomers was established by using a column carrying a chiral
      stationary phase. The HPLC analysis has proven that the stereochemistry of the
      natural epigobiusxanthin is 3R,3'S,6'S. 

PMID- 25561413
TI  - Cancer multicellular spheroids: volume assessment from a single 2D projection.
AB  - Volume is one of the most important features for the characterization of a tumour
      on a macroscopic scale. It is often used to assess the effectiveness of care
      treatments, thus making its correct evaluation a crucial issue for patient care.
      Similarly, volume is a key feature on a microscopic scale. Multicellular cancer
      spheroids are 3D tumour models widely employed in pre-clinical studies to test
      the effects of drugs and radiotherapy treatments. Very few methods have been
      proposed to estimate the tumour volume arising from a 2D projection of
      multicellular spheroids, and even fewer have been designed to provide a 3D
      reconstruction of the tumour shape. In this work, we propose Reconstruction and
      Visualization from a Single Projection (ReViSP), an automatic method conceived to
      reconstruct the 3D surface and estimate the volume of single cancer multicellular
      spheroids, or even of spheroid cultures. As the input parameter ReViSP requires
      only one 2D projection, which could be a widefield microscope image. We assessed
      the effectiveness of our method by comparing it with other approaches. To this
      purpose, we used a new strategy that allowed us to achieve accurate volume
      measurements based on the analysis of home-made 3D objects, built by mimicking
      the spheroid morphology. The results confirmed the effectiveness of our method
      for both 3D reconstruction and volume assessment. ReViSP software is distributed
      as an open source tool. 

PMID- 25561414
TI  - Investigating the effects of plasma pretreatment on the formation of ordered
      aggregates of lysozyme.
AB  - We investigated the influence of plasma pretreatment on fibril formation and
      aggregation properties of lysozyme by using the Congo red binding assay,
      transmission electron microscopy, sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE), far-ultraviolet circular dichroism, and 1
      anilinonaphthalene-8-sulfonic acid (ANS) fluorescence spectroscopy. Our Congo red
      binding and transmission electron microscopy findings indicated that plasma
      pretreatment may suppress the formation of ordered fibrillar lysozyme aggregates.
      The inhibitory effect triggered by plasma pretreatment was observed to be
      positively correlated with the duration of plasma pretreatment. Compared to the
      untreated controls, our ANS fluorescence results suggested that fewer solvent
      exposed hydrophobic clusters in lysozymes were formed upon pretreatment with
      plasma. Moreover, HEWL samples with and without plasma pretreatment showed
      considerably different molecular profiles. We believe the outcome from this work
      may not only help develop potential strategies for the attenuation of ordered
      protein aggregation, which is implicated in amyloid pathology, but also present a
      nice example of plasma-based medicine. 

PMID- 25561415
TI  - Grafting of ionic liquids on stainless steel surface for antibacterial
      application.
AB  - Stainless steel (SS) is favored for many uses due to its excellent chemical
      resistance, thermal stability and mechanical properties. Biofilms can be formed
      on stainless steel and may lead to serious hygiene problems and economic losses
      in many areas, e.g. food processing, public infrastructure and healthcare. For
      the first time, our work endeavored to make SS having antibacterial properties,
      ionic liquids (ILs) were grafted on SS surface via silane treatment followed by
      thiol-ene click reaction. The chemical structure and composition of the ILs
      grafted stainless-steel coupon surfaces were characterized by X-ray photoelectron
      spectroscopy (XPS) and attenuated total reflection-Fourier transform infrared
      (ATR-FTIR) spectroscopy. The antibacterial activity has been investigated, and
      the results showed that the ILs grafted SS surface exhibited significant
      antibacterial effects against Gram-negative Escherichia coli. Additionally, the
      results obtained here indicated that the ILs used here having bromide anion
      showed much better antibacterial activity against E. coli than the corresponding
      ILs with tetrafluoroborate and hexafluorophosphate as anions. These results
      obtained here can help to design novel and more efficient stainless steel having
      antibacterial surface. 

PMID- 25561416
TI  - Reductively-sheddable cationic nanocarriers for dual chemotherapy and gene
      therapy with enhanced release.
AB  - The development of a versatile strategy to synthesize cationic nanocarriers
      capable of co-delivery and enhanced release of drugs and oligonucleotides is
      promising for synergic dual chemotherapy and gene therapy. Herein, we report a
      novel cationic amphiphilic diblock copolymer having a single reduction-responsive
      disulfide linkage at a junction between a FDA-approved polylactide (PLA) block
      and a cationic methacrylate block (C-ssABP). The amphiphilic design of the C
      ssABP enables the formation of cationic micellar aggregates possessing
      hydrophobic PLA cores, encapsulating anticancer drugs; cationic coronas, ensuring
      complementary complexation with negatively-charged oligonucleotides through
      electrostatic interactions; and disulfides at interfaces, leading to enhanced
      release of both encapsulated drugs and complexed oligonucleotides. The reduction
      responsive intracellular trafficking results from flow cytometry, confocal laser
      scanning microscopy, and cell viability, as well as in vitro gene transfection
      assay suggest that C-ssABP offers versatility as an effective nanocarrier
      platform for dual chemotherapy and gene therapy. 

PMID- 25561417
TI  - On the relation of mind wandering and ADHD symptomatology.
AB  - Mind wandering seems to be a prototypical feature of attention
      deficit/hyperactivity disorder (ADHD). However, an important emerging distinction
      of mind-wandering types hinges on whether a given episode of mind wandering
      reflects a failure of executive control (spontaneous mind wandering) or the
      engagement of controlled processes for internal processing (deliberate mind
      wandering). Here we distinguish between spontaneous and deliberate mind wandering
      and test the hypothesis that symptoms of ADHD are associated with the former but
      not the latter. We assessed ADHD symptomatology and everyday levels of deliberate
      and spontaneous mind wandering in two large non-clinical samples (Ns = 1,354). In
      addition, to provide converging evidence, we examined rates of deliberate and
      spontaneous mind wandering in a clinically diagnosed ADHD sample. Results provide
      clear evidence that spontaneous, but not deliberate, mind wandering is a central
      feature of ADHD symptomatology at both the clinical and non-clinical level. We
      discuss the implications of these results for understanding both ADHD and mind
      wandering. 

PMID- 25561418
TI  - Learning, plasticity, and atypical generalization in children with autism.
AB  - Individuals with autism spectrum disorder (ASD) show accelerated learning in some
      tasks, degraded learning in others, and distinct deficits when generalizing to
      novel situations. Recent simulations with connectionist models suggest that
      deficits in cortical plasticity mechanisms can account for atypical patterns of
      generalization shown by some children with ASD. We tested the surprising
      theoretical prediction, from past simulations, that the children with ASD who
      show atypical generalization in perceptual categorization tasks will benefit more
      from training with a single prototypical member of the category than from
      training with multiple examples, but children with ASD who generalize normally
      will be comparatively harmed. The experimental results confirmed this prediction,
      suggesting that plasticity deficits may well underlie the difficulties that some
      children with ASD have generalizing skills, and these deficits are not specific
      to the acquisition of social skills, but rather reflect a more general perceptual
      learning deficit that may impact many abilities.

PMID- 25561419
TI  - Metformin use reduction in mild to moderate renal impairment: possible
      inappropriate curbing of use based on food and drug administration
      contraindications.

PMID- 25561420
TI  - MiR-17-5p up-regulates YES1 to modulate the cell cycle progression and apoptosis
      in ovarian cancer cell lines.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs that participate in the regulation
      of gene expression. Although many studies have demonstrated the involvement of
      miR-17-5p in different cancers, little is known to its function in ovarian
      cancer. In this study, we demonstrated that overexpression of miR-17-5p was able
      to enhance cell proliferation by promoting G1/S transition of the cell cycle and
      suppressing apoptosis in ES-2 and OVCAR3 cell lines, whereas inhibition of miR-17
      5p yielded the reverse phenotype. YES1 was identified as a novel target gene of
      miR-17-5p. Moreover, miR-17-5p was found to directly bind to the 3'UTR of YES1
      mRNA and up-regulated its expression. Furthermore, knockdown of YES1 led to the
      suppression of proliferation and induced cell cycle arrest in ES-2 and OVCAR3
      cells. Ectopic expression of YES1 was able to reverse the effects of miR-17-5p
      inhibition. Collectively, our results indicated that miR-17-5p might play a role
      in human ovarian cancer by up-regulating YES1 expression. J. Cell. Biochem. 116:
      1050-1059, 2015. (c) 2015 Wiley Periodicals, Inc.

PMID- 25561422
TI  - High-performance Ge quantum dot decorated graphene/zinc-oxide heterostructure
      infrared photodetector.
AB  - A novel size-controllable germanium quantum dot (Ge QD) is synthesized and
      decorated onto reduced graphene oxide (RGO) fragments to overcome the low
      infrared (IR) photoresponses (~0.1 A/W)13,14 of pristine graphene. With the
      integration of flexible substrate, monolayer graphene (MLG) electrode and n-type
      zinc oxide (ZnO), a high-performance QD-decorated-RGO/ZnO heterostructure
      infrared photodetector is reported in this study. The Ge QD-decorated-RGO hybrid
      photosensitive composite improves the responsivity (~9.7 A/W, 1400 nm) in IR
      waveband without sacrificing the response speed (~40 MUs rise time and 90 MUs
      recovery time). In addition, the effective barrier formed between graphene and
      ZnO interface restricts the dark current (~1.4 nA, -3 V) to guarantee the
      relatively excellent rectifying behavior and high on/off ratio (~10(3)) for this
      IR photodetector. With these superior inherent properties and micron-sized
      sensing active area, this photodetector manifests great potential in the future
      application of graphene-based IR photodetector. 

PMID- 25561423
TI  - Ultrasound-guided saphenous nerve block is an effective technique for
      perioperative analgesia in ambulatory arthroscopic surgery of the internal knee
      compartment.
AB  - OBJECTIVES: Arthroscopic knee surgery is a minimally invasive technique with
      moderate pain during the first 24h. Our main objective was to evaluate the
      efficacy of ultrasound guided saphenous nerve block as a method of pain control
      intraoperatively and postoperatively for this surgery. MATERIAL AND METHODS: A
      prospective and observational study. All patients received general anesthesia
      with laryngeal mask in the saphenous group, nerve block was performed with 10 ml
      ropivacaine 0.475%. Location of the surgery (external compartment group/internal
      compartment group), morphine consumption, VAS for pain at 5, 30, 60 and 120 min
      and 24 h after surgery, need for rescue medication, onset of nausea and vomiting,
      length of stay in PACU, delayed discharge and satisfaction were evaluated.
      RESULTS: The study included 73 patients. Of these, 46 received saphenous nerve
      block and 27 didn't receive it. Consumption of intraoperative, postoperative and
      total morphine was significantly lower in the saphenous group as well as VAS at
      24h. In the subgroup of internal compartment surgery differences in VAS 24 h,
      morphine consume and lenght of stay in PACU were mantained. CONCLUSIONS: The
      ultrasound-guided block of saphenous nerve, particularly in the internal
      compartment arthroscopic knee surgery, decreases analgesic requirements,
      obtaining more effective pain control in the first 24 h postoperatively and
      without any known side effects.

PMID- 25561424
TI  - [Extraction of foreign body with Arndt(r) bronchial blocker].

PMID- 25561425
TI  - [Attempted suicide by recurrent intentionally foreign object ingest: A challenge
      for the anesthesiologist].

PMID- 25561426
TI  - [The cryoprecipitate: that old unknown].
AB  - Cryoprecipitate is a plasma derivative rich in fibrinogen and other procoagulant
      factors. It has been successfully used for decades in the treatment of the
      coagulopathy of trauma patients, cardiovascular surgery, liver failure and
      disseminated intravascular coagulation. Although cryoprecipitate is routinely
      used in many western countries, most of the Spanish regional blood banks stopped
      its production in the late 1990's. Moreover, in recent years there is a movement
      to replace cryoprecipitate with manufactured fibrinogen concentrate. As a
      consequence, many of the younger anaesthesiologists did not have any direct
      experience with cryoprecipitate. This article aims to describe the
      characteristics of cryoprecipitate since it is a different product from
      manufactured fibrinogen concentrate, with its own specific indications that
      deserve to be further studied in clinical trials. 

PMID- 25561427
TI  - Development and optimization of a new MALDI-TOF protocol for identification of
      the Sporothrix species complex.
AB  - Accurate species identification of the Sporothrix schenckii complex is essential,
      since identification based only on phenotypic characteristics is often
      inconclusive due to phenotypic variability within the species. We used matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) for species identification of 70 environmental and clinical isolates of the
      Sporothrix complex. A reference database was established for MALDI-TOF MS-based
      species identification according to minor adjustments in the manufacturer's
      guidelines. The MALDI-TOF MS clearly distinguished strains of Sporothrix
      brasiliensis, Sporothrix globosa, Sporothrix mexicana, S. schenckii, Sporothrix
      luriei and Sporothrix pallida, enabling identification of all isolates at the
      species level, as confirmed by partial calmodulin gene sequence analyses. The
      present methodology is simple, reliable, rapid and highly suitable for routine
      identification in clinical mycology laboratories and culture collections,
      particularly for updating and reclassifying of deposited Sporothrix isolates. 

PMID- 25561428
TI  - Copper dynamics under alternating redox conditions is influenced by soil
      properties and contamination source.
AB  - Understanding the effect of soil redox conditions on contaminant dynamics is of
      significant importance for evaluating their lability, mobility and potential
      transfer to other environmental compartments. Under changing redox conditions,
      soil properties and constituents such as Fe and Mn (hydr)oxides and organic
      matter (OM) may influence the behavior of associated metallic elements (MEs). In
      this work, the redox-driven release and redistribution of Cu between different
      soil pools was studied in three soils having different contamination sources.
      This was achieved by subjecting soil columns to a series of alternating reducing
      and oxidizing cycles under non-limiting C conditions, and assessing their
      influence on soil pore water, leachate and solid phase composition. Results
      showed that, in all soils, alternating redox conditions led to an increase in the
      distribution of Cu in the more labile fractions, consequently enhancing its
      susceptibility to loss. This was generally linked to the redox-driven cycling of
      Fe, Mn and dissolved organic matter (DOM). In fact, results suggested that the
      reductive dissolution of Fe and Mn (hydr)oxides and subsequent reprecipitation as
      poorly-ordered phases under oxic conditions contributed to the release and
      mobilization of Cu and/or Cu-containing organometallic complexes. However, the
      behavior of Cu, as well as the mechanisms controlling Cu release and loss with
      redox cycling, was influenced by both soil properties (e.g. pH, contents of
      easily reducible Fe and Mn (hydr)oxides) and source of Cu contamination. 

PMID- 25561429
TI  - Association between animal age and the prevalence of Shiga toxin-producing
      Escherichia coli in a cohort of beef cattle.
AB  - Even with advancements in pre- and post-harvest food safety, Shiga toxin
      producing Escherichia coli (STEC) still present challenges to human health. Since
      cattle are the primary reservoir for STEC, lowering the prevalence of this
      pathogen in farm animals may reduce STEC outbreaks in humans. However, because
      many of the factors that modulate the colonization and persistence of STEC in
      cattle remain unknown, reducing STEC in this host is challenging. In this study,
      we evaluated a cohort of beef cattle one to eleven years of age to determine the
      effect of animal age on the prevalence of STEC. During the first year of sample
      collection, heifers had significantly lower STEC prevalence than cows (37.5% vs.
      70%). In the second year of sample collection, STEC prevalence peaked in cows
      that were two years of age and tended to decrease as animals became older. In
      addition, by studying a subset of the animals in both years, we observed an
      increase in STEC prevalence from 40.6% to 53.1% in heifers, whereas cows had a
      net decrease in STEC prevalence from 71.4% to 61.9%. The results from this study
      indicate that animal age is a significant factor that influences the prevalence
      of STEC in cattle. These findings have implications for the development of on
      farm mitigation strategies by targeting animals with the highest risk of
      shedding; it could be possible to reduce pathogen transmission among cattle and
      prevent zoonotic or foodborne transmission to humans. 

PMID- 25561430
TI  - Alteration of a motor learning rule under mirror-reversal transformation does not
      depend on the amplitude of visual error.
AB  - Human's sophisticated motor learning system paradoxically interferes with motor
      performance when visual information is mirror-reversed (MR), because normal
      movement error correction further aggravates the error. This error-increasing
      mechanism makes performing even a simple reaching task difficult, but is overcome
      by alterations in the error correction rule during the trials. To isolate factors
      that trigger learners to change the error correction rule, we manipulated the
      gain of visual angular errors when participants made arm-reaching movements with
      mirror-reversed visual feedback, and compared the rule alteration timing between
      groups with normal or reduced gain. Trial-by-trial changes in the visual angular
      error was tracked to explain the timing of the change in the error correction
      rule. Under both gain conditions, visual angular errors increased under the MR
      transformation, and suddenly decreased after 3-5 trials with increase. The
      increase became degressive at different amplitude between the two groups, nearly
      proportional to the visual gain. The findings suggest that the alteration of the
      error-correction rule is not dependent on the amplitude of visual angular errors,
      and possibly determined by the number of trials over which the errors increased
      or statistical property of the environment. The current results encourage future
      intensive studies focusing on the exact rule-change mechanism. 

PMID- 25561421
TI  - Invariant visual object recognition and shape processing in rats.
AB  - Invariant visual object recognition is the ability to recognize visual objects
      despite the vastly different images that each object can project onto the retina
      during natural vision, depending on its position and size within the visual
      field, its orientation relative to the viewer, etc. Achieving invariant
      recognition represents such a formidable computational challenge that is often
      assumed to be a unique hallmark of primate vision. Historically, this has limited
      the invasive investigation of its neuronal underpinnings to monkey studies, in
      spite of the narrow range of experimental approaches that these animal models
      allow. Meanwhile, rodents have been largely neglected as models of object vision,
      because of the widespread belief that they are incapable of advanced visual
      processing. However, the powerful array of experimental tools that have been
      developed to dissect neuronal circuits in rodents has made these species very
      attractive to vision scientists too, promoting a new tide of studies that have
      started to systematically explore visual functions in rats and mice. Rats, in
      particular, have been the subjects of several behavioral studies, aimed at
      assessing how advanced object recognition and shape processing is in this
      species. Here, I review these recent investigations, as well as earlier studies
      of rat pattern vision, to provide an historical overview and a critical summary
      of the status of the knowledge about rat object vision. The picture emerging from
      this survey is very encouraging with regard to the possibility of using rats as
      complementary models to monkeys in the study of higher-level vision. 

PMID- 25561431
TI  - Tough Al-alginate/poly(N-isopropylacrylamide) hydrogel with tunable LCST for soft
      robotics.
AB  - Tough Al-alginate/poly(N-isopropylacrylamide) (PNIPAM) hydrogel has been
      synthesized by introducing an interpenetrating network with hybrid physically
      cross-linked alginate and chemically cross-linked PNIPAM. Varying the
      concentration of AlCl3 regulates the mechanical properties of the tough hydrogel
      and tunes its lower critical solution temperature (LCST) as well. The tough Al
      alginate/PNIPAM exhibits 6.3 +/- 0.3 MPa of compressive stress and 9.95 of
      uniaxial stretch. Tunability of LCST is also achieved in a wide range within 22.5
      32  degrees C. A bending beam actuator and a four-arm gripper made of bilayer (Na
      alginate/PNIPAM)/(Al-alginate/PNIPAM) hydrogel as prototype of all-hydrogel soft
      robotics are demonstrated. A finite element (FE) simulation model is developed to
      simulate the deformation of the soft robotics. The FE simulation not only
      reproduces the deformation process of performed experiments but also predicts
      more complicated devices that can be explored in the future. This work broadens
      the application of temperature-responsive PNIPAM-based hydrogels. 

PMID- 25561432
TI  - One-pot synthesis of magnetic Ni@Mg(OH)2 core-shell nanocomposites as a
      recyclable removal agent for heavy metals.
AB  - A surfactant-assisted hydrothermal route has been presented to one-pot
      synthesized Ni nanoparticles encapsulated in Mg(OH)2 hollow spheres. The diameter
      of Ni cores and the thickness of Mg(OH)2 shells are about 60-80 and 15 nm,
      respectively, and the size of a whole composite sphere is approximately 70-100
      nm. Benefiting from the ferrimagnetic behavior of Ni cores and the high surface
      area of Mg(OH)2 shells, Ni@Mg(OH)2 nanocomposites exhibit excellent heavy metals
      adsorption capacity and recyclable property. The first removal efficiency is
      almost 100% for target metals, and after five cycles, the adsorption capacity
      remains 95%. A series of experiments show the adsorption of heavy metal ions on
      Ni@Mg(OH)2 follows a pseudo-second order kinetic equation and can be described by
      a Langmuir isotherm model. 

PMID- 25561433
TI  - Temporal Changes in Left Ventricular Systolic Function and Use of
      Echocardiography in Adult Heart Donors.
AB  - BACKGROUND: One reason for refusal of donor hearts is the development of left
      ventricular systolic dysfunction, a condition reported to occur in up to 42 % of
      adults with brain death. Prior studies have suggested that appropriate donor
      management and evaluation of cardiac dysfunction with serial echocardiography
      (TTE) can improve organ procurement. The aims of our study are to examine the
      prevalence and describe longitudinal changes in cardiac dysfunction after brain
      death. METHODS: A cross-sectional study was performed using the Life Center
      Northwest organ database to identify potential adult heart donors diagnosed with
      brain death between January 2011 and November 2013. 246 potential donors with at
      least one TTE following brain death were identified. 58 donors received serial
      TTEs. Echocardiograms were reviewed for cardiac dysfunction, defined as left
      ventricular ejection fraction (EF) <50 % and/or presence of regional wall motion
      abnormalities. RESULTS: Cardiac dysfunction was present in 74 (30 %) patients.
      Age, body mass index, EF, and proportion of harvested organs differed
      significantly between the groups with and without cardiac dysfunction. Among
      patients receiving serial TTEs, 29 patients had cardiac dysfunction on initial
      TTE, with 15 (52 %) of these patients demonstrating resolved cardiac dysfunction
      over time leading to organ harvest. CONCLUSIONS: To our knowledge, the present
      study is the largest study describing the use of serial TTE and its utilization
      in adult donors. The prevalence of cardiac dysfunction after adult brain death is
      high, but given enough time and support, many of these donors have improvement in
      cardiac function, ultimately leading to transplantation.

PMID- 25561434
TI  - Metronidazole-induced encephalopathy: not always a reversible situation.
AB  - BACKGROUND: Metronidazole is a nitroimidazole antimicrobial drug prescribed to
      treat infections caused by anaerobic bacteria and protozoa. Uncommonly, it causes
      central nervous system (CNS) toxicity manifesting as metronidazole-induced
      encephalopathy (MIE). METHODS: Case report. RESULTS: A 65-year-old woman with
      hepatitis B cirrhosis (Child-Pugh class C, MELD 21) developed progressive
      encephalopathy to GCS 4 during a 3-week course of metronidazole for
      cholecystitis. Initial MRI was consistent with CNS metronidazole toxicity, with
      symmetrical T2 hyperintensity and generally restricted diffusion in bilateral
      dentate nuclei, corpus callosum, midbrain, superior cerebellar peduncles,
      internal capsules, and cerebral white matter. Laboratory values did not
      demonstrate significant electrolyte shifts, and continuous EEG was without
      seizure. High-dose thiamine was empirically administered. Lumbar puncture was not
      performed due to coagulopathy and thrombocytopenia. Despite discontinuation of
      metronidazole and keeping ammonia levels near normal, the patient did not
      improve. MRI was repeated 1 week after discontinuation of metronidazole. Although
      there was decreased DWI hyperintensity in the dentate nuclei, diffuse T2
      hyperintensity persisted and even progressed in the brainstem, basal ganglia, and
      subcortical white matter. Petechial hemorrhages developed in bilateral
      corticospinal tracts and subcortical white matter. T1 hypointensity appeared in
      the corpus callosum. She was transitioned to comfort measures only and died 12
      days later. CONCLUSION: MIE is an uncommon adverse effect of treatment with
      metronidazole that characteristically affects the dentate nuclei but may also
      involve the brainstem, corpus callosum, subcortical white matter, and basal
      ganglia. While the clinical symptoms and neuroimaging changes are usually
      reversible, persistent encephalopathy with poor outcome may occur.

PMID- 25561435
TI  - Decision Aids and Shared Decision-Making in Neurocritical Care: An Unmet Need in
      Our NeuroICUs.
AB  - Improved resuscitation methods and advances in critical care have significantly
      increased the survival of patients presenting with devastating brain injuries
      compared to prior decades. After the patient's stabilization phase, families and
      patients are faced with "goals-of-care" decisions about continuation of
      aggressive intensive care unit care or comfort care only (CMO). Highly varying
      rates of CMO between centers raise the question of "self-fulfilling prophecies."
      Disease severity, the physician's communication and the family's understanding of
      projected outcomes, their uncertainties, complication risks with continued care,
      physician bias, and the patient's and surrogate's wishes and values all influence
      a CMO decision. Disease-specific decision support interventions, decision aids
      (DAs), may remedy these issues in the neurocritical care unit, potentially
      leading to better-informed and less-biased goals-of-care decisions in
      neurocritically ill patients, while increasing decision knowledge, confidence,
      and realistic expectations and decreasing decisional conflict and regret. Shared
      decision-making (SDM) is a collaborative process that enhances patients' and
      proxies' understanding about prognosis, encourages them to actively weigh the
      risks and benefits of a treatment, and considers the patient's preferences and
      values to make better decisions. DAs are SDM tools, which have been successfully
      implemented for many other conditions to assist difficult decision-making. In
      this article, we summarize the purposes of SDM, the derivation of DAs, and their
      potential application in neurocritical care. 

PMID- 25561436
TI  - TiO2 nanotube array photoelectrocatalyst and Ni-Sb-SnO2 electrocatalyst bifacial
      electrodes: a new type of bifunctional hybrid platform for water treatment.
AB  - Bifunctional hybrid electrodes capable of generating various reactive oxygen
      species (ROS) over a wide range of potentials were developed by coupling
      electrocatalysts and photoelectrocatalysts. To achieve this, Ni-doped Sb-SnO2
      (NSS) was deposited on one side of a titanium (Ti) foil while the other side was
      anodized to grow a TiO2 nanotube array (TNA) for electrochemical ozone generation
      and photoelectrochemical hydroxyl radical generation, respectively. Surface
      characterization indicated that NSS and TNA were formed and spatially separated
      yet electrically connected through the Ti substrate. While each catalyst
      possessed unique electrochemical properties, the coupling of both catalysts
      resulted in mixed electrochemical properties that drove electrocatalysis at high
      potentials and photoelectrocatalysis at low potentials. The performance of the
      NSS/TNA electrode for phenol decomposition was ~3 times greater than that of
      single-layer catalysts and ~1.5 times greater than the combined catalytic
      performances of the individual NSS and TNA catalysts. This synergistic effect was
      attributed partly to the simultaneous generation of hydroxyl radicals and ozone,
      followed by the production of other ROS. A mechanism for the generation of ROS
      was discussed. 

PMID- 25561437
TI  - Silibinin Prevents Autophagic Cell Death upon Oxidative Stress in Cortical
      Neurons and Cerebral Ischemia-Reperfusion Injury.
AB  - Neuronal apoptosis and oxidative stress are involved in most of the
      neurodegenerative diseases, promoting neuron survival is critical for therapy.
      Silibinin (SLB), which is derived from the seeds of Silybinisus laborinum L., has
      been widely used as an antioxidant. Here we tested the neuroprotective effects of
      SLB and the involved molecular mechanisms. We demonstrated that SLB promoted
      neuron viability upon hydrogen peroxide (H2O2) challenge and reduced
      hypoxia/ischemia injury in the middle cerebral artery occlusion (MCAO) mouse
      model. SLB reversed the decreased level of procaspase-3 and balanced Bcl-2 and
      Bax expression upon H2O2 insult to inhibit cell apoptosis. Furthermore, SLB
      suppressed the activation of autophagy by decreasing microtubule-associated
      protein 1 light chain 3 (LC3-II) and Beclin-1 levels under oxidative stress
      accordingly. SLB phosphorylated protein kinase B (Akt-1) at Ser473 in a time- and
      dose-dependent manner. The inhibitor for phosphoinositide-3-kinase (PI3K)
      wortmannin abrogated SLB-induced phosphorylation of Akt-1 and mTOR, decreased the
      suppression of autophagy, and therefore abolished SLB-mediated neuroprotection.
      All the data suggested that SLB protected neurons by inhibiting both the
      mitochondrial and autophagic cell death pathways. This study opens new avenues
      for the use of SLB in treatment of central nervous system (CNS) diseases in which
      oxidative stress plays a major role in disease pathogenesis. Given that it occurs
      naturally with low toxicity and pleiotropic effects that benefit the nervous
      system, SLB acts potentially as a novel therapy for ischemic injury. 

PMID- 25561439
TI  - Facile conversion of commercial coarse-type LiCoO2 to nanocomposite-separated
      nanolayer architectures as a way for electrode performance enhancement.
AB  - Coarse-type LiCoO2 is the state-of-the-art cathode material in small-scale
      lithium-ion batteries (LIBs); however, poor rate performance and cycling
      stability limit its large-scale applications. Here we report the modification of
      coarse-type LiCoO2 (LCO) with nanosized lithium lanthanum titanate (Li3xLa2/3
      xTiO3, LLTO) through a facile sol-gel process, the electrochemical performance of
      commercial LiCoO2 is improved effectively, in particular at high rates. The
      crystalline structure of pristine LiCoO2 is not affected by the introduction of
      the LLTO phase, while nanosized LLTO particles are likely incorporated into the
      space of the LiCoO2 layers to form a LCO-LLTO nanocomposite, which separate the
      LCO layers with the increase of layer spacing to ~100 nm. The LLTO incorporation
      through the facile post-treatment effectively reduces the charge-transfer
      resistance and increases the electrode reactions; consequently, the LLTO
      incorporated LCO electrode shows higher capacity than LiCoO2 at a higher rate and
      prolonging cycling stability in both potential ranges of 2.7-4.2 V and 2.7-4.5 V,
      making it also suitable for high-rate operation. This novel concept is general,
      which may also be applicable to other electrode materials. It thus introduces a
      new way for the development of high rate-performance electrodes for LIBs for
      large scale applications such as electric vehicles and electrochemical energy
      storage for smart grids. 

PMID- 25561440
TI  - Editorial: Old dog, new tricks: proangiogenic effect of adenosine via stimulation
      of thrombospondin-1 in macrophages.

PMID- 25561441
TI  - Editorial: Where's the B in NHP?

PMID- 25561442
TI  - Photochromic organic nanoparticles as innovative platforms for plasmonic
      nanoassemblies.
AB  - The fabrication of hybrid core-shell nanoassemblies involving a nondoped azo
      photochromic core coated with a dense shell of gold nanoparticles is reported to
      investigate the influence of localized plasmons onto the azo core
      photoisomerization. Photochromic organic nanoparticles, regarded as a novel class
      of high-density photoswitchable nanomaterials, are first elaborated upon
      precipitation in water of push-pull azo molecules, containing sulfur-terminated
      units to chelate gold nanoparticles. Photoisomerization studies of the azo
      nanoparticles reveal significantly higher E -> Z photoconversion yields and Z ->
      E thermal back relaxation rate constants compared to those of dyes processed as
      thin films and in solution, respectively. These unexpected results are ascribed
      to the large surface-to-volume ratio and cooperative effects encountered in
      nanoparticles that deform without disassembling under polarized illumination as a
      result of the weak change in the azo dipole moment. UV-vis spectroscopy and Raman
      microscopy of the hybrid nanoassemblies show strong optical coupling between both
      photoactive constituents, confirming that gold nanoparticles are tightly
      positioned on the azo core surface. Such coupling causes partial quenching of the
      azo photoisomerization but does not impact the thermal back relaxation. Longer
      sulfur-terminated chains provide reduced quenching of the photoreaction by the
      localized plasmons, thereby opening perspectives toward plasmon-mediated
      deformation of nano-objects for light-controlled nanomechanics. 

PMID- 25561443
TI  - Guest-editorial: Telehealth systems and applications.

PMID- 25561444
TI  - Guest-editorial: Biomedical informatics in clinical environments.

PMID- 25561445
TI  - Improvement of force-sensor-based heart rate estimation using multichannel data
      fusion.
AB  - The aim of this paper is to present and evaluate algorithms for heartbeat
      interval estimation from multiple spatially distributed force sensors integrated
      into a bed. Moreover, the benefit of using multichannel systems as opposed to a
      single sensor is investigated. While it might seem intuitive that multiple
      channels are superior to a single channel, the main challenge lies in finding
      suitable methods to actually leverage this potential. To this end, two algorithms
      for heart rate estimation from multichannel vibration signals are presented and
      compared against a single-channel sensing solution. The first method operates by
      analyzing the cepstrum computed from the average spectra of the individual
      channels, while the second method applies Bayesian fusion to three interval
      estimators, such as the autocorrelation, which are applied to each channel. This
      evaluation is based on 28 night-long sleep lab recordings during which an eight
      channel polyvinylidene fluoride-based sensor array was used to acquire cardiac
      vibration signals. The recruited patients suffered from different sleep disorders
      of varying severity. From the sensor array data, a virtual single-channel signal
      was also derived for comparison by averaging the channels. The single-channel
      results achieved a beat-to-beat interval error of 2.2% with a coverage (i.e.,
      percentage of the recording which could be analyzed) of 68.7%. In comparison, the
      best multichannel results attained a mean error and coverage of 1.0% and 81.0%,
      respectively. These results present statistically significant improvements of
      both metrics over the single-channel results (p < 0.05).

PMID- 25561446
TI  - Low-power wireless ECG acquisition and classification system for body sensor
      networks.
AB  - A low-power biosignal acquisition and classification system for body sensor
      networks is proposed. The proposed system consists of three main parts: 1) a high
      pass sigma delta modulator-based biosignal processor (BSP) for signal acquisition
      and digitization, 2) a low-power, super-regenerative on-off keying transceiver
      for short-range wireless transmission, and 3) a digital signal processor (DSP)
      for electrocardiogram (ECG) classification. The BSP and transmitter circuits,
      which are the body-end circuits, can be operated for over 80 days using two 605
      mAH zinc-air batteries as the power supply; the power consumption is 586.5 MUW.
      As for the radio frequency receiver and DSP, which are the receiving-end circuits
      that can be integrated in smartphones or personal computers, power consumption is
      less than 1 mW. With a wavelet transform-based digital signal processing circuit
      and a diagnosis control by cardiologists, the accuracy of beat detection and ECG
      classification are close to 99.44% and 97.25%, respectively. All chips are
      fabricated in TSMC 0.18-MUm standard CMOS process.

PMID- 25561447
TI  - Implementation of a wireless ECG acquisition SoC for IEEE 802.15.4 (ZigBee)
      applications.
AB  - This paper presents a wireless biosignal acquisition system-on-a-chip (WBSA-SoC)
      specialized for electrocardiogram (ECG) monitoring. The proposed system consists
      of three subsystems, namely, 1) the ECG acquisition node, 2) the protocol for
      standard IEEE 802.15.4 ZigBee system, and 3) the RF transmitter circuits. The
      ZigBee protocol is adopted for wireless communication to achieve high
      integration, applicability, and portability. A fully integrated CMOS RF front end
      containing a quadrature voltage-controlled oscillator and a 2.4-GHz low-IF (i.e.,
      zero-IF) transmitter is employed to transmit ECG signals through wireless
      communication. The low-power WBSA-SoC is implemented by the TSMC 0.18-MUm
      standard CMOS process. An ARM-based displayer with FPGA demodulation and an RF
      receiver with analog-to-digital mixed-mode circuits are constructed as
      verification platform to demonstrate the wireless ECG acquisition system.
      Measurement results on the human body show that the proposed SoC can effectively
      acquire ECG signals.

PMID- 25561448
TI  - Enhancing the pulse contour analysis-based arterial stiffness estimation using a
      novel photoplethysmographic parameter.
AB  - In this paper, we propose a novel method for enhancing pulse contour analysis
      based arterial stiffness estimation using a simple and low-complexity
      photoplethysmographic parameter (P2Ocd). The method first eliminates baseline
      wanders in the digital volume pulse (DVP) by applying a simple morphological
      filter. The filtered DVP signal is then transformed into a slope sum function
      signal to simplify the pulse peak detection process by enhancing the upslope of
      the DVP signal while suppressing its downslope. An adaptive thresholding scheme
      is applied to detect pulse peaks from the transformed signal. Pulse onsets are
      then identified as the minimum values between consecutive pulse peaks. The P2Ocd
      is finally calculated by dividing the time interval between the pulse peak and
      the pulse onset by the pulse length. In order to assess the agreement of the
      P2Ocd with an established technique, brachial-ankle pulse wave velocity, we
      performed Bland-Altman and correlation analyses. Furthermore, we evaluated the
      P2Ocd-based arterial stiffness estimation in terms of prediction accuracy (%
      error rate) and repeatability (coefficient of variation). The results show that
      the proposed measurement agrees well with the established technique and shows a
      high repeatability; it also has a better predictive accuracy than that of
      conventional methods. In addition, we show that the proposed parameter further
      improves the predictive accuracy by combining it with age. The proposed method is
      therefore highly applicable to small ubiquitous healthcare applications. 

PMID- 25561438
TI  - The Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in
      Alzheimer's Disease.
AB  - One of the shared hallmarks of neurodegenerative diseases is the accumulation of
      misfolded proteins. Therefore, it is suspected that normal proteostasis is
      crucial for neuronal survival in the brain and that the malfunction of this
      mechanism may be the underlying cause of neurodegenerative diseases. The
      accumulation of amyloid plaques (APs) composed of amyloid-beta peptide (Abeta)
      aggregates and neurofibrillary tangles (NFTs) composed of misfolded Tau proteins
      are the defining pathological markers of Alzheimer's disease (AD). The
      accumulation of these proteins indicates a faulty protein quality control in the
      AD brain. An impaired ubiquitin-proteasome system (UPS) could lead to negative
      consequences for protein regulation, including loss of function. Another pivotal
      mechanism for the prevention of misfolded protein accumulation is the utilization
      of molecular chaperones. Molecular chaperones, such as heat shock proteins (HSPs)
      and FK506-binding proteins (FKBPs), are highly involved in protein regulation to
      ensure proper folding and normal function. In this review, we elaborate on the
      molecular basis of AD pathophysiology using recent data, with a particular focus
      on the role of the UPS and molecular chaperones as the defensive mechanism
      against misfolded proteins that have prion-like properties. In addition, we
      propose a rational therapy approach based on this mechanism. 

PMID- 25561449
TI  - Characterization of depressive States in bipolar patients using wearable textile
      technology and instantaneous heart rate variability assessment.
AB  - The analysis of cognitive and autonomic responses to emotionally relevant stimuli
      could provide a viable solution for the automatic recognition of different mood
      states, both in normal and pathological conditions. In this study, we present a
      methodological application describing a novel system based on wearable textile
      technology and instantaneous nonlinear heart rate variability assessment, able to
      characterize the autonomic status of bipolar patients by considering only
      electrocardiogram recordings. As a proof of this concept, our study presents
      results obtained from eight bipolar patients during their normal daily activities
      and being elicited according to a specific emotional protocol through the
      presentation of emotionally relevant pictures. Linear and nonlinear features were
      computed using a novel point-process-based nonlinear autoregressive integrative
      model and compared with traditional algorithmic methods. The estimated indices
      were used as the input of a multilayer perceptron to discriminate the depressive
      from the euthymic status. Results show that our system achieves much higher
      accuracy than the traditional techniques. Moreover, the inclusion of
      instantaneous higher order spectra features significantly improves the accuracy
      in successfully recognizing depression from euthymia.

PMID- 25561450
TI  - Cluster-based analysis for personalized stress evaluation using physiological
      signals.
AB  - Technology development in wearable sensors and biosignal processing has made it
      possible to detect human stress from the physiological features. However, the
      intersubject difference in stress responses presents a major challenge for
      reliable and accurate stress estimation. This research proposes a novel cluster
      based analysis method to measure perceived stress using physiological signals,
      which accounts for the intersubject differences. The physiological data are
      collected when human subjects undergo a series of task-rest cycles, incurring
      varying levels of stress that is indicated by an index of the State Trait Anxiety
      Inventory. Next, a quantitative measurement of stress is developed by analyzing
      the physiological features in two steps: 1) a k -means clustering process to
      divide subjects into different categories (clusters), and 2) cluster-wise stress
      evaluation using the general regression neural network. Experimental results show
      a significant improvement in evaluation accuracy as compared to traditional
      methods without clustering. The proposed method is useful in developing
      intelligent, personalized products for human stress management.

PMID- 25561451
TI  - Human-computer interface controlled by the lip.
AB  - Lip control system is an innovative human-computer interface specially designed
      for people with tetraplegia. This paper presents an evaluation of the lower lip
      potential to control an input device, according to Fitts' law (ISO/TS 9241
      411:2012 standard). The results show that the lower lip throughput is comparable
      with the thumb throughput using the same input device under the same conditions.
      These results establish the baseline for future research studies about the lower
      lip capacity to operate a computer input device.

PMID- 25561452
TI  - Quantification of wave reflection using peripheral blood pressure waveforms.
AB  - This paper presents a novel minimally invasive method for quantifying blood
      pressure (BP) wave reflection in the arterial tree. In this method, two
      peripheral BP waveforms are analyzed to obtain an estimate of central aortic BP
      waveform, which is used together with a peripheral BP waveform to compute forward
      and backward pressure waves. These forward and backward waves are then used to
      quantify the strength of wave reflection in the arterial tree. Two unique
      strengths of the proposed method are that 1) it replaces highly invasive central
      aortic BP and flow waveforms required in many existing methods by less invasive
      peripheral BP waveforms, and 2) it does not require estimation of characteristic
      impedance. The feasibility of the proposed method was examined in an experimental
      swine subject under a wide range of physiologic states and in 13 cardiac surgery
      patients. In the swine subject, the method was comparable to the reference method
      based on central aortic BP and flow. In cardiac surgery patients, the method was
      able to estimate forward and backward pressure waves in the absence of any
      central aortic waveforms: on the average, the root-mean-squared error between
      actual versus computed forward and backward pressure waves was less than 5 mmHg,
      and the error between actual versus computed reflection index was less than 0.03.

PMID- 25561453
TI  - SleepAp: an automated obstructive sleep apnoea screening application for
      smartphones.
AB  - Obstructive sleep apnoea (OSA) is a sleep disorder with long-term consequences.
      Long-term effects include sleep-related issues and cardiovascular diseases. OSA
      is often diagnosed with an overnight sleep test called a polysomnogram.
      Monitoring can be costly with long wait times for diagnosis. In this paper, a
      novel OSA screening framework and prototype phone application are introduced. A
      database of 856 patients that underwent at-home polygraphy was collected.
      Features were derived from audio, actigraphy, photoplethysmography (PPG), and
      demographics, and used as the inputs of a support vector machine (SVM)
      classifier. The SVM was trained on 735 patients and tested on 121 patients.
      Classification on the test set had an accuracy of up to 92.2% when classifying
      subjects as having moderate or severe OSA versus being healthy or a snorer based
      on the clinicians' diagnoses. The signal processing and machine learning
      algorithms were ported to Java and integrated into the phone application-SleepAp.
      SleepAp records the body position, audio, actigraphy and PPG signals, and
      implements the clinically validated STOP-BANG questionnaire. It derives features
      from the signals and classifies the user as having OSA or not using the SVM
      trained on the clinical database. The resulting software could provide a new,
      easy-to-use, low-cost, and widely available modality for OSA screening.

PMID- 25561454
TI  - Carotid intraplaque neovascularization quantification software (CINQS).
AB  - Intraplaque neovascularization (IPN) is an important biomarker of atherosclerotic
      plaque vulnerability. As IPN can be detected by contrast enhanced ultrasound
      (CEUS), imaging-biomarkers derived from CEUS may allow early prediction of plaque
      vulnerability. To select the best quantitative imaging-biomarkers for prediction
      of plaque vulnerability, a systematic analysis of IPN with existing and new
      analysis algorithms is necessary. Currently available commercial contrast
      quantification tools are not applicable for quantitative analysis of carotid IPN
      due to substantial motion of the carotid artery, artifacts, and intermittent
      perfusion of plaques. We therefore developed a specialized software package
      called Carotid intraplaque neovascularization quantification software (CINQS). It
      was designed for effective and systematic comparison of sets of quantitative
      imaging biomarkers. CINQS includes several analysis algorithms for carotid IPN
      quantification and overcomes the limitations of current contrast quantification
      tools and existing carotid IPN quantification approaches. CINQS has a modular
      design which allows integrating new analysis tools. Wizard-like analysis tools
      and its graphical-user-interface facilitate its usage. In this paper, we describe
      the concept, analysis tools, and performance of CINQS and present analysis
      results of 45 plaques of 23 patients. The results in 45 plaques showed excellent
      agreement with visual IPN scores for two quantitative imaging-biomarkers (The
      area under the receiver operating characteristic curve was 0.92 and 0.93).

PMID- 25561455
TI  - Automatic 3-D segmentation of endocardial border of the left ventricle from
      ultrasound images.
AB  - The segmentation of the left ventricle (LV) is an important task to assess the
      cardiac function in ultrasound images of the heart. This paper presents a novel
      methodology for the segmentation of the LV in three-dimensional (3-D)
      echocardiographic images based on the probabilistic data association filter
      (PDAF). The proposed methodology begins by initializing a 3-D deformable model
      either semiautomatically, with user input, or automatically, and it comprises the
      following feature hierarchical approach: 1) edge detection in the vicinity of the
      surface (low-level features); 2) edge grouping to obtain potential LV surface
      patches (mid-level features); and 3) patch filtering using a shape-PDAF framework
      (high-level features). This method provides good performance accuracy in 20
      echocardiographic volumes, and compares favorably with the state-of-the-art
      segmentation methodologies proposed in the recent literature.

PMID- 25561456
TI  - Breast segmentation and density estimation in breast MRI: a fully automatic
      framework.
AB  - Breast density measurement is an important aspect in breast cancer diagnosis as
      dense tissue has been related to the risk of breast cancer development. The
      purpose of this study is to develop a method to automatically compute breast
      density in breast MRI. The framework is a combination of image processing
      techniques to segment breast and fibroglandular tissue. Intra- and interpatient
      signal intensity variability is initially corrected. The breast is segmented by
      automatically detecting body-breast and air-breast surfaces. Subsequently,
      fibroglandular tissue is segmented in the breast area using expectation
      maximization. A dataset of 50 cases with manual segmentations was used for
      evaluation. Dice similarity coefficient (DSC), total overlap, false negative
      fraction (FNF), and false positive fraction (FPF) are used to report similarity
      between automatic and manual segmentations. For breast segmentation, the proposed
      approach obtained DSC, total overlap, FNF, and FPF values of 0.94, 0.96, 0.04,
      and 0.07, respectively. For fibroglandular tissue segmentation, we obtained DSC,
      total overlap, FNF, and FPF values of 0.80, 0.85, 0.15, and 0.22, respectively.
      The method is relevant for researchers investigating breast density as a risk
      factor for breast cancer and all the described steps can be also applied in
      computer aided diagnosis systems.

PMID- 25561457
TI  - Multiple hypotheses image segmentation and classification with application to
      dietary assessment.
AB  - We propose a method for dietary assessment to automatically identify and locate
      food in a variety of images captured during controlled and natural eating events.
      Two concepts are combined to achieve this: a set of segmented objects can be
      partitioned into perceptually similar object classes based on global and local
      features; and perceptually similar object classes can be used to assess the
      accuracy of image segmentation. These ideas are implemented by generating
      multiple segmentations of an image to select stable segmentations based on the
      classifier's confidence score assigned to each segmented image region. Automatic
      segmented regions are classified using a multichannel feature classification
      system. For each segmented region, multiple feature spaces are formed. Feature
      vectors in each of the feature spaces are individually classified. The final
      decision is obtained by combining class decisions from individual feature spaces
      using decision rules. We show improved accuracy of segmenting food images with
      classifier feedback.

PMID- 25561458
TI  - A novel data-mining approach leveraging social media to monitor consumer opinion
      of sitagliptin.
AB  - A novel data mining method was developed to gauge the experience of the drug
      Sitagliptin (trade name Januvia) by patients with diabetes mellitus type 2. To
      this goal, we devised a two-step analysis framework. Initial exploratory analysis
      using self-organizing maps was performed to determine structures based on user
      opinions among the forum posts. The results were a compilation of user's clusters
      and their correlated (positive or negative) opinion of the drug. Subsequent
      modeling using network analysis methods was used to determine influential users
      among the forum members. These findings can open new avenues of research into
      rapid data collection, feedback, and analysis that can enable improved outcomes
      and solutions for public health and important feedback for the manufacturer.

PMID- 25561459
TI  - Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT
      and artery wall thickness in patients with FHA.
AB  - Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects
      of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia
      (FHA), are characterized by decreased tissue cholesterol removal and an increased
      atherogenic burden. We performed an open-label uncontrolled proof-of-concept
      study to evaluate the effect of infusions with a human apoA-I-containing HDL
      mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects
      received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed
      by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux,
      fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery
      wall inflammation by (18)F-fluorodeoxyglucose-positron emission
      tomography/computed tomography scans. We included seven FHA patients: HDL
      cholesterol (HDL-c), 13.8 [1.8-29.1] mg/dl; apoA-I, 28.7 [7.9-59.1] mg/dl.
      Following nine infusions in 1 month, apoA-I and HDL-c increased directly after
      infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative
      increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward
      increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel
      wall area decreased compared with baseline from 25.0 to 22.8 mm(2) (P = 0.043)
      and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects,
      CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and
      inflammation, supporting further evaluation of CER-001 in FHA patients. 

PMID- 25561460
TI  - Protein unfolding allows use of commercial antibodies in an apolipoprotein M
      sandwich ELISA.
AB  - apoM is a member of the lipocalin superfamily and circulates in plasma attached
      to HDL particles. apoM plays a role in cholesterol metabolism and has recently
      been identified as transporter for the signaling lipid, sphingosine-1-phosphate
      (S1P), in plasma. S1P is implicated in several inflammatory diseases such as
      multiple sclerosis and rheumatoid arthritis. The ability to accurately measure
      apoM is crucial for investigating its biological functions and possible clinical
      implications. However, reliable commercial methods have been lacking so far.
      Therefore, we have developed an assay that specifically recognizes human apoM in
      plasma using commercially available reagents. Commercial apoM antibodies were
      screened for compatibility in a sandwich ELISA-based assay. One optimal pair of
      antibodies was chosen, and sample preparation, buffers, and incubation times were
      optimized to generate a simple and reproducible method. Validation and comparison
      to a previously described ELISA for apoM confirmed that the assay displays a high
      degree of sensitivity, specificity, and precision. Our results show that
      commercially available antibodies can be used to accurately measure human plasma
      apoM. This method can be implemented in every laboratory and will help promote
      high quality research. 

PMID- 25561461
TI  - Phosphatidylinositol inhibits respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) infects nearly all children under age 2, and
      reinfection occurs throughout life, seriously impacting adults with chronic
      pulmonary diseases. Recent data demonstrate that the anionic pulmonary surfactant
      lipid phosphatidylglycerol (PG) exerts a potent antiviral effect against RSV in
      vitro and in vivo. Phosphatidylinositol (PI) is also an anionic pulmonary
      surfactant phospholipid, and we tested its antiviral activity. PI liposomes
      completely suppress interleukin-8 production from BEAS2B epithelial cells
      challenged with RSV. The presence of PI during viral challenge in vitro reduces
      infection by a factor of >10(3). PI binds RSV with high affinity, preventing
      virus attachment to epithelial cells. Intranasal inoculation with PI along with
      RSV in mice reduces the viral burden 30-fold, eliminates the influx of
      inflammatory cells, and reduces tissue histopathology. Pharmacological doses of
      PI persist for >6 h in mouse lung. Pretreatment of mice with PI at 2 h prior to
      viral infection effectively suppresses inflammation and reduces the viral burden
      by 85%. These data demonstrate that PI has potent antiviral properties, a long
      residence time in the extracellular bronchoalveolar compartment, and a
      significant prophylaxis window. The findings demonstrate PG and PI have
      complementary roles as intrinsic, innate immune antiviral mediators in the lung. 

PMID- 25561463
TI  - The twisting tale of woolly hair: a trait with many causes.
AB  - Woolly hair is an uncommon condition among non-black people, which may be an
      isolated finding or associated with additional clinical symptoms. When woolly
      hair is accompanied by palmoplantar keratoderma, it may herald a deadly
      cardiomyopathy, and therefore this condition should alert the physician for a
      heart disorder. Until recently, the underlying causes for this rare phenotype
      were obscure, and only three genes were associated with this condition. However,
      in recent years, many more genes were found to underlie this disorder, uncovering
      new molecular pathways. Better knowledge of the different mechanisms that control
      the curliness of hair may offer new treatment options for this condition, and may
      also make it possible to affect hair texture in general. 

PMID- 25561464
TI  - Ebola, dynamin, and the cordon sanitaire of Dr. Adrien Proust.

PMID- 25561465
TI  - FASEB Science Research Conference on phospholipid cell signaling and metabolism
      in inflammation and cancer.

PMID- 25561462
TI  - HDL from apoA1 transgenic mice expressing the 4WF isoform is resistant to
      oxidative loss of function.
AB  - HDL functions are impaired by myeloperoxidase (MPO), which selectively targets
      and oxidizes human apoA1. We previously found that the 4WF isoform of human
      apoA1, in which the four tryptophan residues are substituted with phenylalanine,
      is resistant to MPO-mediated loss of function. The purpose of this study was to
      generate 4WF apoA1 transgenic mice and compare functional properties of the 4WF
      and wild-type human apoA1 isoforms in vivo. Male mice had significantly higher
      plasma apoA1 levels than females for both isoforms of human apoA1, attributed to
      different production rates. With matched plasma apoA1 levels, 4WF transgenics had
      a trend for slightly less HDL-cholesterol versus human apoA1 transgenics. While
      4WF transgenics had 31% less reverse cholesterol transport (RCT) to the plasma
      compartment, equivalent RCT to the liver and feces was observed. Plasma from both
      strains had similar ability to accept cholesterol and facilitate ex vivo
      cholesterol efflux from macrophages. Furthermore, we observed that 4WF transgenic
      HDL was partially (~50%) protected from MPO-mediated loss of function while human
      apoA1 transgenic HDL lost all ABCA1-dependent cholesterol acceptor activity. In
      conclusion, the structure and function of HDL from 4WF transgenic mice was not
      different than HDL derived from human apoA1 transgenic mice. 

PMID- 25561468
TI  - Stability of proICA512/IA-2 and its targeting to insulin secretory granules
      require beta4-sheet-mediated dimerization of its ectodomain in the endoplasmic
      reticulum.
AB  - The type 1 diabetes autoantigen ICA512/IA-2/RPTPN is a receptor protein tyrosine
      phosphatase of the insulin secretory granules (SGs) which regulates the size of
      granule stores, possibly via cleavage/signaling of its cytosolic tail. The role
      of its extracellular region remains unknown. Structural studies indicated that
      beta2- or beta4-strands in the mature ectodomain (ME ICA512) form dimers in
      vitro. Here we show that ME ICA512 prompts proICA512 dimerization in the
      endoplasmic reticulum. Perturbation of ME ICA512 beta2-strand N-glycosylation
      upon S508A replacement allows for proICA512 dimerization, O-glycosylation,
      targeting to granules, and conversion, which are instead precluded upon G553D
      replacement in the ME ICA512 beta4-strand. S508A/G553D and N506A/G553D double
      mutants dimerize but remain in the endoplasmic reticulum. Removal of the N
      terminal fragment (ICA512-NTF) preceding ME ICA512 allows an ICA512-DeltaNTF
      G553D mutant to exit the endoplasmic reticulum, and ICA512-DeltaNTF is
      constitutively delivered to the cell surface. The signal for SG sorting is
      located within the NTF RESP18 homology domain (RESP18-HD), whereas soluble NTF is
      retained in the endoplasmic reticulum. Hence, we propose that the ME ICA512 beta2
      strand fosters proICA512 dimerization until NTF prevents N506 glycosylation.
      Removal of this constraint allows for proICA512 beta4-strand-induced
      dimerization, exit from the endoplasmic reticulum, O-glycosylation, and RESP18-HD
      mediated targeting to granules. 

PMID- 25561471
TI  - Waste management training and capacity building for local authorities in
      developing countries.

PMID- 25561469
TI  - Characterization of human cyclin-dependent kinase 12 (CDK12) and CDK13 complexes
      in C-terminal domain phosphorylation, gene transcription, and RNA processing.
AB  - Cyclin-dependent kinase 9 (CDK9) and CDK12 have each been demonstrated to
      phosphorylate the RNA polymerase II C-terminal domain (CTD) at serine 2 of the
      heptad repeat, both in vitro and in vivo. CDK9, as part of P-TEFb and the super
      elongation complex (SEC), is by far the best characterized of CDK9, CDK12, and
      CDK13. We employed both in vitro and in vivo assays to further investigate the
      molecular properties of CDK12 and its paralog CDK13. We isolated Flag-tagged
      CDK12 and CDK13 and found that they associate with numerous RNA processing
      factors. Although knockdown of CDK12, CDK13, or their cyclin partner CCNK did not
      affect the bulk CTD phosphorylation levels in HCT116 cells, transcriptome
      sequencing (RNA-seq) analysis revealed that CDK12 and CDK13 losses in HCT116
      cells preferentially affect expression of DNA damage response and snoRNA genes,
      respectively. CDK12 and CDK13 depletion also leads to a loss of expression of RNA
      processing factors and to defects in RNA processing. These findings suggest that
      in addition to implementing CTD phosphorylation, CDK12 and CDK13 may affect RNA
      processing through direct physical interactions with RNA processing factors and
      by regulating their expression. 

PMID- 25561472
TI  - Corrigendum.
AB  - Identification of thermophilic and mesophilic bacteria and fungi in Esfahan
      (Iran) municipal solid waste compost by Ghazifard et al., Waste Manag Res June
      2001; 19: 257-261, doi: 10.1177/0734242X0101900307. In the above paper the fourth
      author's name was misspelt, the correct spelling is below: Zahra Etemadifar. 

PMID- 25561470
TI  - Regulation of the transcription factor EB-PGC1alpha axis by beclin-1 controls
      mitochondrial quality and cardiomyocyte death under stress.
AB  - In cardiac ischemia-reperfusion injury, reactive oxygen species (ROS) generation
      and upregulation of the hypoxia-inducible protein BNIP3 result in mitochondrial
      permeabilization, but impairment in autophagic removal of damaged mitochondria
      provokes programmed cardiomyocyte death. BNIP3 expression and ROS generation
      result in upregulation of beclin-1, a protein associated with transcriptional
      suppression of autophagy-lysosome proteins and reduced activation of
      transcription factor EB (TFEB), a master regulator of the autophagy-lysosome
      machinery. Partial beclin-1 knockdown transcriptionally stimulates lysosome
      biogenesis and autophagy via mTOR inhibition and activation of TFEB, enhancing
      removal of depolarized mitochondria. TFEB activation concomitantly stimulates
      mitochondrial biogenesis via PGC1alpha induction to restore normally polarized
      mitochondria and attenuate BNIP3- and hypoxia-reoxygenation-induced cell death.
      Conversely, overexpression of beclin-1 activates mTOR to inhibit TFEB, resulting
      in declines in lysosome numbers and suppression of PGC1alpha transcription.
      Importantly, knockdown of endogenous TFEB or PGC1alpha results in a complete or
      partial loss, respectively, of the cytoprotective effects of partial beclin-1
      knockdown, indicating a critical role for both mitochondrial autophagy and
      biogenesis in ensuring cellular viability. These studies uncover a
      transcriptional feedback loop for beclin-1-mediated regulation of TFEB activation
      and implicate a central role for TFEB in coordinating mitochondrial autophagy
      with biogenesis to restore normally polarized mitochondria and prevent ischemia
      reperfusion-induced cardiomyocyte death. 

PMID- 25561474
TI  - Changing indications for pediatric heart transplantation: complex congenital
      heart disease.

PMID- 25561476
TI  - Diagnosis and resolution of Loeffler endocarditis secondary to eosinophilic
      granulomatosis with polyangiitis demonstrated by cardiac magnetic resonance-T2
      mapping.

PMID- 25561477
TI  - Transdiaphragmatic rupture of hepatic abscess producing purulent pericarditis and
      pericardial tamponade.

PMID- 25561479
TI  - Cardiology patient page. Spontaneous coronary artery dissection (SCAD).

PMID- 25561480
TI  - Letter by Dai et al regarding article, "ST-elevation myocardial infarction
      diagnosed after hospital admission".

PMID- 25561481
TI  - Response to letter regarding article, "ST-elevation myocardial infarction
      diagnosed after hospital admission".

PMID- 25561482
TI  - Letter by Khan and Moukarbel regarding article, "Risk for myocardial infarction
      and stroke after community-acquired bacteremia: a 20-year population-based cohort
      study".

PMID- 25561483
TI  - Response to letter regarding article, "Risk for myocardial infarction and stroke
      after community-acquired bacteremia: a 20-year population-based cohort study".

PMID- 25561484
TI  - Can psychedelic compounds play a part in drug dependence therapy?
AB  - After a 40-year hiatus there is now a revisiting of psychedelic drug therapy
      throughout psychiatry, with studies examining the drugs psilocybin, ketamine,
      ibogaine and ayahuasca in the treatment of drug dependence. Limitations to these
      therapies are both clinical and legal, but the possibility of improving outcomes
      for patients with substance dependency imposes an obligation to research this
      area. 

PMID- 25561485
TI  - Making a medicine out of MDMA.
AB  - From its first use 3,4,-methylenedioxymethamphetamine (MDMA) has been recognised
      as a drug with therapeutic potential. Research on its clinical utility stopped
      when it entered the recreational drug scene but has slowly resurrected in the
      past decade. Currently there is enough evidence for MDMA to be removed from its
      Schedule 1 status of 'no medical use' and moved into Schedule 2 (alongside other
      misused but useful medicines such as heroin and amphetamine). Such a regulatory
      move would liberate its use as a medicine for patients experiencing severe mental
      illnesses such as treatment-resistant post-traumatic stress disorder. 

PMID- 25561486
TI  - Efficacy of cognitive bias modification interventions in anxiety and depression:
      meta-analysis.
AB  - BACKGROUND: Cognitive bias modification (CBM) interventions are strongly
      advocated in research and clinical practice. AIMS: To examine the efficiency of
      CBM for clinically relevant outcomes, along with study quality, publication bias
      and potential moderators. METHOD: We included randomised controlled trials (RCTs)
      of CBM interventions that reported clinically relevant outcomes assessed with
      standardised instruments. RESULTS: We identified 49 trials and grouped outcomes
      into anxiety and depression. Effect sizes were small considering all the samples,
      and mostly non-significant for patient samples. Effect sizes became non
      significant when outliers were excluded and after adjustment for publication
      bias. The quality of the RCTs was suboptimal. CONCLUSIONS: CBM may have small
      effects on mental health problems, but it is also very well possible that there
      are no significant clinically relevant effects. Research in this field is
      hampered by small and low-quality trials, and by risk of publication bias. Many
      positive outcomes are driven by extreme outliers.

PMID- 25561487
TI  - Invited commentary on . . . Word use in first-person accounts of schizophrenia.
AB  - The use of pronouns and causal attributions in personal accounts has been
      analysed to distinguish between schizophrenia and mood disorders. The
      implications for both cognitive processing and the underlying pathology of
      symptoms are explored. Context is identified as a key variable in the analysis
      and interpretation of text. 

PMID- 25561488
TI  - Can we predict switch from unipolar depression to bipolar disorder?

PMID- 25561489
TI  - Authors' reply.

PMID- 25561490
TI  - Correction.

PMID- 25561492
TI  - A laminin 511 matrix is regulated by TAZ and functions as the ligand for the
      alpha6Bbeta1 integrin to sustain breast cancer stem cells.
AB  - Understanding how the extracellular matrix impacts the function of cancer stem
      cells (CSCs) is a significant but poorly understood problem. We report that
      breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and
      tumor initiation by engaging the alpha6Bbeta1 integrin and activating the Hippo
      transducer TAZ. Although TAZ is important for the function of breast CSCs, the
      mechanism is unknown. We observed that TAZ regulates the transcription of the
      alpha5 subunit of LM511 and the formation of a LM511 matrix. These data establish
      a positive feedback loop involving TAZ and LM511 that contributes to stemness in
      breast cancer. 

PMID- 25561493
TI  - Initiation and maintenance of pluripotency gene expression in the absence of
      cohesin.
AB  - Cohesin is implicated in establishing and maintaining pluripotency. Whether this
      is because of essential cohesin functions in the cell cycle or in gene regulation
      is unknown. Here we tested cohesin's contribution to reprogramming in systems
      that reactivate the expression of pluripotency genes in the absence of
      proliferation (embryonic stem [ES] cell heterokaryons) or DNA replication
      (nuclear transfer). Contrary to expectations, cohesin depletion enhanced the
      ability of ES cells to initiate somatic cell reprogramming in heterokaryons. This
      was explained by increased c-Myc (Myc) expression in cohesin-depleted ES cells,
      which promoted DNA replication-dependent reprogramming of somatic fusion
      partners. In contrast, cohesin-depleted somatic cells were poorly reprogrammed in
      heterokaryons, due in part to defective DNA replication. Pluripotency gene
      induction was rescued by Myc, which restored DNA replication, and by nuclear
      transfer, where reprogramming does not require DNA replication. These results
      redefine cohesin's role in pluripotency and reveal a novel function for Myc in
      promoting the replication-dependent reprogramming of somatic nuclei. 

PMID- 25561494
TI  - Stably paused genes revealed through inhibition of transcription initiation by
      the TFIIH inhibitor triptolide.
AB  - Transcription by RNA polymerase II (Pol II) in metazoans is regulated in several
      steps, including preinitiation complex (PIC) formation, initiation, Pol II
      escape, productive elongation, cotranscriptional RNA processing, and termination.
      Genome-wide studies have demonstrated that the phenomenon of promoter-bound Pol
      II pausing is widespread, especially for genes involved in developmental and
      stimulus-responsive pathways. However, a mechanistic understanding of the paused
      Pol II state at promoters is limited. For example, at a global level, it is
      unclear to what extent the engaged paused Pol II is stably tethered to the
      promoter or undergoes rapid cycles of initiation and termination. Here we used
      the small molecule triptolide (TPL), an XPB/TFIIH inhibitor, to block
      transcriptional initiation and then measured Pol II occupancy by chromatin
      immunoprecipitation (ChIP) followed by next-generation sequencing (ChIP-seq).
      This inhibition of initiation enabled us to investigate different states of
      paused Pol II. Specifically, our global analysis revealed that most genes with
      paused Pol II, as defined by a pausing index, show significant clearance of Pol
      II during the period of TPL treatment. Our study further identified a group of
      genes with unexpectedly stably paused Pol II, with unchanged Pol II occupancy
      even after 1 h of inhibition of initiation. This group of genes constitutes a
      small portion of all paused genes defined by the conventional criterion of
      pausing index. These findings could pave the way for evaluating the contribution
      of different elongation/pausing factors on different states of Pol II pausing in
      developmental and other stimulus-responsive pathways. 

PMID- 25561495
TI  - Common and distinct DNA-binding and regulatory activities of the BEN-solo
      transcription factor family.
AB  - Recently, the BEN (BANP, E5R, and NAC1) domain was recognized as a new class of
      conserved DNA-binding domain. The fly genome encodes three proteins that bear
      only a single BEN domain ("BEN-solo" factors); namely, Insensitive (Insv), Bsg25A
      (Elba1), and CG9883 (Elba2). Insv homodimers preferentially bind CCAATTGG
      palindromes throughout the genome to mediate transcriptional repression, whereas
      Bsg25A and Elba2 heterotrimerize with their obligate adaptor, Elba3 (i.e., the
      ELBA complex), to recognize a CCAATAAG motif in the Fab-7 insulator. While these
      data suggest distinct DNA-binding properties of BEN-solo proteins, we performed
      reporter assays that indicate that both Bsg25A and Elba2 can individually
      recognize Insv consensus sites efficiently. We confirmed this by solving the
      structure of Bsg25A complexed to the Insv site, which showed that key aspects of
      the BEN:DNA recognition strategy are similar between these proteins. We next show
      that both Insv and ELBA proteins are competent to mediate transcriptional
      repression via Insv consensus sequences but that the ELBA complex appears to be
      selective for the ELBA site. Reciprocally, genome-wide analysis reveals that Insv
      exhibits significant cobinding to class I insulator elements, indicating that it
      may also contribute to insulator function. Indeed, we observed abundant Insv
      binding within the Hox complexes with substantial overlaps with class I
      insulators, many of which bear Insv consensus sites. Moreover, Insv
      coimmunoprecipitates with the class I insulator factor CP190. Finally, we
      observed that Insv harbors exclusive activity among fly BEN-solo factors with
      respect to regulation of Notch-mediated cell fate choices in the peripheral
      nervous system. This in vivo activity is recapitulated by BEND6, a mammalian BEN
      solo factor that conserves the Notch corepressor function of Insv but not its
      capacity to bind Insv consensus sites. Altogether, our data define an array of
      common and distinct biochemical and functional properties of this new family of
      transcription factors. 

PMID- 25561497
TI  - A novel mechanism for Prp5 function in prespliceosome formation and proofreading
      the branch site sequence.
AB  - The DEAD-box RNA helicase Prp5 is required for the formation of the
      prespliceosome through an ATP-dependent function to remodel U2 small nuclear
      ribonucleoprotein particles (snRNPs) and an ATP-independent function of unknown
      mechanism. Prp5 has also been implicated in proofreading the branch site
      sequence, but the molecular mechanism has not been well characterized. Using
      actin precursor mRNA (pre-mRNA) carrying branch site mutations, we identified a
      Prp5-containing prespliceosome with Prp5 directly bound to U2 small nuclear RNA
      (snRNA). Prp5 is in contact with U2 in regions on and near the branchpoint
      interacting stem-loop (BSL), suggesting that Prp5 may function in stabilizing the
      BSL. Regardless of its ATPase activity, Prp5 mutants that suppress branch site
      mutations associate with the spliceosome less tightly and allow more tri-snRNP
      binding for the reaction to proceed. Our results suggest a novel mechanism for
      how Prp5 functions in prespliceosome formation and proofreading of the branch
      site sequence. Prp5 binds to the spliceosome in association with U2 by
      interacting with the BSL and is released upon the base-pairing of U2 with the
      branch site to allow the recruitment of the tri-snRNP. Mutations impairing U2
      branch site base-pairing retard Prp5 release and impede tri-snRNP association.
      Prp5 mutations that destabilize the Prp5-U2 interaction suppress branch site
      mutations by allowing progression of the pathway. 

PMID- 25561496
TI  - Detained introns are a novel, widespread class of post-transcriptionally spliced
      introns.
AB  - Deep sequencing of embryonic stem cell RNA revealed many specific internal
      introns that are significantly more abundant than the other introns within
      polyadenylated transcripts; we classified these as "detained" introns (DIs). We
      identified thousands of DIs, many of which are evolutionarily conserved, in human
      and mouse cell lines as well as the adult mouse liver. DIs can have half-lives of
      over an hour yet remain in the nucleus and are not subject to nonsense-mediated
      decay (NMD). Drug inhibition of Clk, a stress-responsive kinase, triggered rapid
      splicing changes for a specific subset of DIs; half showed increased splicing,
      and half showed increased intron detention, altering transcript pools of >300
      genes. Srsf4, which undergoes a dramatic phosphorylation shift in response to Clk
      kinase inhibition, regulates the splicing of some DIs, particularly in genes
      encoding RNA processing and splicing factors. The splicing of some DIs-including
      those in Mdm4, a negative regulator of p53-was also altered following DNA damage.
      After 4 h of Clk inhibition, the expression of >400 genes changed significantly,
      and almost one-third of these are p53 transcriptional targets. These data suggest
      a widespread mechanism by which the rate of splicing of DIs contributes to the
      level of gene expression. 

PMID- 25561498
TI  - The G-patch protein Spp2 couples the spliceosome-stimulated ATPase activity of
      the DEAH-box protein Prp2 to catalytic activation of the spliceosome.
AB  - Structural rearrangement of the activated spliceosome (B(act)) to yield a
      catalytically active complex (B*) is mediated by the DEAH-box NTPase Prp2 in
      cooperation with the G-patch protein Spp2. However, how the energy of ATP
      hydrolysis by Prp2 is coupled to mechanical work and what role Spp2 plays in this
      process are unclear. Using a purified splicing system, we demonstrate that Spp2
      is not required to recruit Prp2 to its bona fide binding site in the B(act)
      spliceosome. In the absence of Spp2, the B(act) spliceosome efficiently triggers
      Prp2's NTPase activity, but NTP hydrolysis is not coupled to ribonucleoprotein
      (RNP) rearrangements leading to catalytic activation of the spliceosome.
      Transformation of the B(act) to the B* spliceosome occurs only when Spp2 is
      present and is accompanied by dissociation of Prp2 and a reduction in its NTPase
      activity. In the absence of spliceosomes, Spp2 enhances Prp2's RNA-dependent
      ATPase activity without affecting its RNA affinity. Our data suggest that Spp2
      plays a major role in coupling Prp2's ATPase activity to remodeling of the
      spliceosome into a catalytically active machine. 

PMID- 25561500
TI  - Identification of caveolar resident proteins in ventricular myocytes using a
      quantitative proteomic approach: dynamic changes in caveolar composition
      following adrenoceptor activation.
AB  - The lipid raft concept proposes that membrane environments enriched in
      cholesterol and sphingolipids cluster certain proteins and form platforms to
      integrate cell signaling. In cardiac muscle, caveolae concentrate signaling
      molecules and ion transporters, and play a vital role in adrenergic regulation of
      excitation-contraction coupling, and consequently cardiac contractility.
      Proteomic analysis of cardiac caveolae is hampered by the presence of
      contaminants that have sometimes, erroneously, been proposed to be resident in
      these domains. Here we present the first unbiased analysis of the proteome of
      cardiac caveolae, and investigate dynamic changes in their protein constituents
      following adrenoreceptor (AR) stimulation. Rat ventricular myocytes were treated
      with methyl-beta-cyclodextrin (MbetaCD) to deplete cholesterol and disrupt
      caveolae. Buoyant caveolin-enriched microdomains (BCEMs) were prepared from
      MbetaCD-treated and control cell lysates using a standard discontinuous sucrose
      gradient. BCEMs were harvested, pelleted, and resolubilized, then alkylated,
      digested, and labeled with iTRAQ reagents, and proteins identified by LC-MS/MS on
      a LTQ Orbitrap Velos Pro. Proteins were defined as BCEM resident if they were
      consistently depleted from the BCEM fraction following MbetaCD treatment.
      Selective activation of alpha-, beta1-, and beta2-AR prior to preparation of
      BCEMs was achieved by application of agonist/antagonist pairs for 10 min in
      populations of field-stimulated myocytes. We typically identified 600-850
      proteins per experiment, of which, 249 were defined as high-confidence BCEM
      residents. Functional annotation clustering indicates cardiac BCEMs are enriched
      in integrin signaling, guanine nucleotide binding, ion transport, and insulin
      signaling clusters. Proteins possessing a caveolin binding motif were poorly
      enriched in BCEMs, suggesting this is not the only mechanism that targets
      proteins to caveolae. With the notable exception of the cavin family, very few
      proteins show altered abundance in BCEMs following AR activation, suggesting
      signaling complexes are preformed in BCEMs to ensure a rapid and high fidelity
      response to adrenergic stimulation in cardiac muscle. 

PMID- 25561501
TI  - An enhanced in vivo stable isotope labeling by amino acids in cell culture
      (SILAC) model for quantification of drug metabolism enzymes.
AB  - Many of the enzymes involved in xenobiotic metabolism are maintained at a low
      basal level and are only synthesized in response to activation of upstream
      sensor/effector proteins. This induction can have implications in a variety of
      contexts, particularly during the study of the pharmacokinetics,
      pharmacodynamics, and drug-drug interaction profile of a candidate therapeutic
      compound. Previously, we combined in vivo SILAC material with a targeted high
      resolution single ion monitoring (tHR/SIM) LC-MS/MS approach for quantification
      of 197 peptide pairs, representing 51 drug metabolism enzymes (DME), in mouse
      liver. However, as important enzymes (for example, cytochromes P450 (Cyp) of the
      1a and 2b subfamilies) are maintained at low or undetectable levels in the liver
      of unstimulated metabolically labeled mice, quantification of these proteins was
      unreliable. In the present study, we induced DME expression in labeled mice
      through synchronous ligand-mediated activation of multiple upstream nuclear
      receptors, thereby enhancing signals for proteins including Cyps 1a, 2a, 2b, 2c,
      and 3a. With this enhancement, 115 unique, lysine-containing, Cyp-derived
      peptides were detected in the liver of a single animal, as opposed to 56 in a
      pooled sample from three uninduced animals. A total of 386 peptide pairs were
      quantified by tHR/SIM, representing 68 Phase I, 30 Phase II, and eight control
      proteins. This method was employed to quantify changes in DME expression in the
      hepatic cytochrome P450 reductase null (HRN) mouse. We observed compensatory
      induction of several enzymes, including Cyps 2b10, 2c29, 2c37, 2c54, 2c55, 2e1,
      3a11, and 3a13, carboxylesterase (Ces) 2a, and glutathione S-transferases (Gst)
      m2 and m3, along with down-regulation of hydroxysteroid dehydrogenases (Hsd) 11b1
      and 17b6. Using DME-enhanced in vivo SILAC material with tHR/SIM, therefore,
      permits the robust analysis of multiple DME of importance to xenobiotic
      metabolism, with improved utility for the study of drug pharmacokinetics,
      pharmacodynamics, and of chemically treated and genetically modified mouse
      models. 

PMID- 25561502
TI  - Global analysis of myocardial peptides containing cysteines with irreversible
      sulfinic and sulfonic acid post-translational modifications.
AB  - Cysteine (Cys) oxidation is a crucial post-translational modification (PTM)
      associated with redox signaling and oxidative stress. As Cys is highly reactive
      to oxidants it forms a range of post-translational modifications, some that are
      biologically reversible (e.g. disulfides, Cys sulfenic acid) and others (Cys
      sulfinic [Cys-SO2H] and sulfonic [Cys-SO3H] acids) that are considered
      "irreversible." We developed an enrichment method to isolate Cys-SO2H/SO3H
      containing peptides from complex tissue lysates that is compatible with tandem
      mass spectrometry (MS/MS). The acidity of these post-translational modification
      (pKa Cys-SO3H < 0) creates a unique charge distribution when localized on tryptic
      peptides at acidic pH that can be utilized for their purification. The method is
      based on electrostatic repulsion of Cys-SO2H/SO3H-containing peptides from
      cationic resins (i.e. "negative" selection) followed by "positive" selection
      using hydrophilic interaction liquid chromatography. Modification of strong
      cation exchange protocols decreased the complexity of initial flowthrough
      fractions by allowing for hydrophobic retention of neutral peptides. Coupling of
      strong cation exchange and hydrophilic interaction liquid chromatography allowed
      for increased enrichment of Cys-SO2H/SO3H (up to 80%) from other modified
      peptides. We identified 181 Cys-SO2H/SO3H sites from rat myocardial tissue
      subjected to physiologically relevant concentrations of H2O2 (<100 MUm) or to
      ischemia/reperfusion (I/R) injury via Langendorff perfusion. I/R significantly
      increased Cys-SO2H/SO3H-modified peptides from proteins involved in energy
      utilization and contractility, as well as those involved in oxidative damage and
      repair. 

PMID- 25561503
TI  - Quantitative phosphoproteomics of the ataxia telangiectasia-mutated (ATM) and
      ataxia telangiectasia-mutated and rad3-related (ATR) dependent DNA damage
      response in Arabidopsis thaliana.
AB  - The reversible phosphorylation of proteins on serine, threonine, and tyrosine
      residues is an important biological regulatory mechanism. In the context of
      genome integrity, signaling cascades driven by phosphorylation are crucial for
      the coordination and regulation of DNA repair. The two serine/threonine protein
      kinases ataxia telangiectasia-mutated (ATM) and Ataxia telangiectasia-mutated and
      Rad3-related (ATR) are key factors in this process, each specific for different
      kinds of DNA lesions. They are conserved across eukaryotes, mediating the
      activation of cell-cycle checkpoints, chromatin modifications, and regulation of
      DNA repair proteins. We designed a novel mass spectrometry-based
      phosphoproteomics approach to study DNA damage repair in Arabidopsis thaliana.
      The protocol combines filter aided sample preparation, immobilized metal affinity
      chromatography, metal oxide affinity chromatography, and strong cation exchange
      chromatography for phosphopeptide generation, enrichment, and separation.
      Isobaric labeling employing iTRAQ (isobaric tags for relative and absolute
      quantitation) was used for profiling the phosphoproteome of atm atr double
      mutants and wild type plants under either regular growth conditions or challenged
      by irradiation. A total of 10,831 proteins were identified and 15,445 unique
      phosphopeptides were quantified, containing 134 up- and 38 down-regulated ATM/ATR
      dependent phosphopeptides. We identified known and novel ATM/ATR targets such as
      LIG4 and MRE11 (needed for resistance against ionizing radiation), PIE1 and SDG26
      (implicated in chromatin remodeling), PCNA1, WAPL, and PDS5 (implicated in DNA
      replication), and ASK1 and HTA10 (involved in meiosis). 

PMID- 25561505
TI  - Proteomics links the redox state to calcium signaling during bleaching of the
      scleractinian coral Acropora microphthalma on exposure to high solar irradiance
      and thermal stress.
AB  - Shipboard experiments were each performed over a 2 day period to examine the
      proteomic response of the symbiotic coral Acropora microphthalma exposed to acute
      conditions of high temperature/low light or high light/low temperature stress.
      During these treatments, corals had noticeably bleached. The photosynthetic
      performance of residual algal endosymbionts was severely impaired but showed
      signs of recovery in both treatments by the end of the second day. Changes in the
      coral proteome were determined daily and, using recently available annotated
      genome sequences, the individual contributions of the coral host and algal
      endosymbionts could be extracted from these data. Quantitative changes in
      proteins relevant to redox state and calcium metabolism are presented. Notably,
      expression of common antioxidant proteins was not detected from the coral host
      but present in the algal endosymbiont proteome. Possible roles for elevated
      carbonic anhydrase in the coral host are considered: to restore intracellular pH
      diminished by loss of photosynthetic activity, to indirectly limit intracellular
      calcium influx linked with enhanced calmodulin expression to impede late-stage
      symbiont exocytosis, or to enhance inorganic carbon transport to improve the
      photosynthetic performance of algal symbionts that remain in hospite. Protein
      effectors of calcium-dependent exocytosis were present in both symbiotic
      partners. No caspase-family proteins associated with host cell apoptosis, with
      exception of the autophagy chaperone HSP70, were detected, suggesting that algal
      loss and photosynthetic dysfunction under these experimental conditions were not
      due to host-mediated phytosymbiont destruction. Instead, bleaching occurred by
      symbiont exocytosis and loss of light-harvesting pigments of algae that remain in
      hospite. These proteomic data are, therefore, consistent with our premise that
      coral endosymbionts can mediate their own retention or departure from the coral
      host, which may manifest as "symbiont shuffling" of Symbiodinium clades in
      response to environmental stress. 

PMID- 25561504
TI  - The proteome and lipidome of Synechocystis sp. PCC 6803 cells grown under light
      activated heterotrophic conditions.
AB  - Cyanobacteria are photoautotrophic prokaryotes with a plant-like photosynthetic
      machinery. Because of their short generation times, the ease of their genetic
      manipulation, and the limited size of their genome and proteome, cyanobacteria
      are popular model organisms for photosynthetic research. Although the principal
      mechanisms of photosynthesis are well-known, much less is known about the
      biogenesis of the thylakoid membrane, hosting the components of the
      photosynthetic, and respiratory electron transport chain in cyanobacteria. Here
      we present a detailed proteome analysis of the important model and host organism
      Synechocystis sp. PCC 6803 under light-activated heterotrophic growth conditions.
      Because of the mechanistic importance and severe changes in thylakoid membrane
      morphology under light-activated heterotrophic growth conditions, a focus was put
      on the analysis of the membrane proteome, which was supported by a targeted
      lipidome analysis. In total, 1528 proteins (24.5% membrane integral) were
      identified in our analysis. For 641 of these proteins quantitative information
      was obtained by spectral counting. Prominent changes were observed for proteins
      associated with oxidative stress response and protein folding. Because of the
      heterotrophic growth conditions, also proteins involved in carbon metabolism and
      C/N-balance were severely affected. Although intracellular thylakoid membranes
      were significantly reduced, only minor changes were observed in their protein
      composition. The increased proportion of the membrane-stabilizing sulfoqinovosyl
      diacyl lipids found in the lipidome analysis, as well as the increased content of
      lipids with more saturated acyl chains, are clear indications for a coordinated
      synthesis of proteins and lipids, resulting in stabilization of intracellular
      thylakoid membranes under stress conditions. 

PMID- 25561506
TI  - Reproducible and consistent quantification of the Saccharomyces cerevisiae
      proteome by SWATH-mass spectrometry.
AB  - Targeted mass spectrometry by selected reaction monitoring (S/MRM) has proven to
      be a suitable technique for the consistent and reproducible quantification of
      proteins across multiple biological samples and a wide dynamic range. This
      performance profile is an important prerequisite for systems biology and
      biomedical research. However, the method is limited to the measurements of a few
      hundred peptides per LC-MS analysis. Recently, we introduced SWATH-MS, a
      combination of data independent acquisition and targeted data analysis that
      vastly extends the number of peptides/proteins quantified per sample, while
      maintaining the favorable performance profile of S/MRM. Here we applied the SWATH
      MS technique to quantify changes over time in a large fraction of the proteome
      expressed in Saccharomyces cerevisiae in response to osmotic stress. We sampled
      cell cultures in biological triplicates at six time points following the
      application of osmotic stress and acquired single injection data independent
      acquisition data sets on a high-resolution 5600 tripleTOF instrument operated in
      SWATH mode. Proteins were quantified by the targeted extraction and integration
      of transition signal groups from the SWATH-MS datasets for peptides that are
      proteotypic for specific yeast proteins. We consistently identified and
      quantified more than 15,000 peptides and 2500 proteins across the 18 samples. We
      demonstrate high reproducibility between technical and biological replicates
      across all time points and protein abundances. In addition, we show that the
      abundance of hundreds of proteins was significantly regulated upon osmotic shock,
      and pathway enrichment analysis revealed that the proteins reacting to osmotic
      shock are mainly involved in the carbohydrate and amino acid metabolism. Overall,
      this study demonstrates the ability of SWATH-MS to efficiently generate
      reproducible, consistent, and quantitatively accurate measurements of a large
      fraction of a proteome across multiple samples. 

PMID- 25561508
TI  - Locally advanced gastroesophageal junction tumor: a treatment dilemma.
AB  - Over the last several decades, the incidence of adenocarcinoma of the
      gastroesophageal junction (GEJ) has been increasing in developed countries.
      Although complete surgical resection remains the cornerstone of treatment for
      resectable disease, long-term outcomes are poor and recurrence rates are high
      with surgery alone in patients presenting with locally advanced disease.
      Multimodal therapy has been shown to improve survival; however, the optimal
      therapeutic approach remains controversial, and practices vary across the world.
      Preoperative chemoradiotherapy is generally used in the U.S., whereas
      perioperative chemotherapy without radiation is favored in most European
      countries. In this review, we discuss why the treatment of locally advanced GEJ
      tumors remains controversial, examine the evidence for various multimodal
      approaches, discuss their respective pros and cons, evaluate the role of
      radiation therapy, highlight some ongoing and planned clinical trials, and
      suggest areas that need further research. 

PMID- 25561507
TI  - Compound loss of function of nuclear receptors Tr2 and Tr4 leads to induction of
      murine embryonic beta-type globin genes.
AB  - The orphan nuclear receptors TR2 and TR4 have been shown to play key roles in
      repressing the embryonic and fetal globin genes in erythroid cells. However,
      combined germline inactivation of Tr2 and Tr4 leads to periimplantation lethal
      demise in inbred mice. Hence, we have previously been unable to examine the
      consequences of their dual loss of function in adult definitive erythroid cells.
      To circumvent this issue, we generated conditional null mutants in both genes and
      performed gene inactivation in vitro in adult bone marrow cells. Compound Tr2/Tr4
      loss of function led to induced expression of the embryonic epsilony and betah1
      globins (murine counterparts of the human epsilon- and gamma-globin genes).
      Additionally, TR2/TR4 function is required for terminal erythroid cell
      maturation. Loss of TR2/TR4 abolished their occupancy on the epsilony and betah1
      gene promoters, and concurrently impaired co-occupancy by interacting
      corepressors. These data strongly support the hypothesis that the TR2/TR4 core
      complex is an adult stage-specific, gene-selective repressor of the embryonic
      globin genes. Detailed mechanistic understanding of the roles of TR2/TR4 and
      their cofactors in embryonic and fetal globin gene repression may ultimately
      enhance the discovery of novel therapeutic agents that can effectively inhibit
      their transcriptional activity and be safely applied to the treatment of beta
      globinopathies. 

PMID- 25561509
TI  - Breaking bad news in Bolivia.

PMID- 25561510
TI  - Advances in anticancer immunotoxin therapy.
AB  - Immunotoxins are a novel class of antibody-conjugated therapeutics currently in
      clinical development for a variety of malignancies. They consist of an antibody
      based targeting domain fused to a bacterial toxin payload for cell killing.
      Immunotoxins kill cells by inhibiting protein synthesis, a unique mechanism of
      action that is toxic to both dividing and nondividing cells. Recent advances in
      the design and administration of immunotoxins are overcoming historical
      challenges in the field, leading to renewed interest in these therapeutics. 

PMID- 25561511
TI  - Genomic classifier ColoPrint predicts recurrence in stage II colorectal cancer
      patients more accurately than clinical factors.
AB  - BACKGROUND: Approximately 20% of patients with stage II colorectal cancer will
      experience a relapse. Current clinical-pathologic stratification factors do not
      allow clear identification of these high-risk patients. ColoPrint (Agendia,
      Amsterdam, The Netherlands, http://www.agendia.com) is a gene expression
      classifier that distinguishes patients with low or high risk of disease relapse.
      METHODS: ColoPrint was developed using whole-genome expression data and validated
      in several independent validation cohorts. Stage II patients from these studies
      were pooled (n = 416), and ColoPrint was compared with clinical risk factors
      described in the National Comprehensive Cancer Network (NCCN) 2013 Guidelines for
      Colon Cancer. Median follow-up was 81 months. Most patients (70%) did not receive
      adjuvant chemotherapy. Risk of relapse (ROR) was defined as survival until first
      event of recurrence or death from cancer. RESULTS: In the pooled stage II data
      set, ColoPrint identified 63% of patients as low risk with a 5-year ROR of 10%,
      whereas high-risk patients (37%) had a 5-year ROR of 21%, with a hazard ratio
      (HR) of 2.16 (p = .004). This remained significant in a multivariate model that
      included number of lymph nodes retrieved and microsatellite instability. In the
      T3 microsatellite-stable subgroup (n = 301), ColoPrint classified 59% of patients
      as low risk with a 5-year ROR of 9.9%. High-risk patients (31%) had a 22.4% ROR
      (HR: 2.41; p = .005). In contrast, the NCCN clinical high-risk factors were
      unable to distinguish high- and low-risk patients (15% vs. 13% ROR; p = .55).
      CONCLUSION: ColoPrint significantly improved prognostic accuracy independent of
      microsatellite status or clinical variables, facilitating the identification of
      patients at higher risk who might be considered for additional treatment.

PMID- 25561513
TI  - Opioids for low back pain.
AB  - Back pain affects most adults, causes disability for some, and is a common reason
      for seeking healthcare. In the United States, opioid prescription for low back
      pain has increased, and opioids are now the most commonly prescribed drug class.
      More than half of regular opioid users report back pain. Rates of opioid
      prescribing in the US and Canada are two to three times higher than in most
      European countries. The analgesic efficacy of opioids for acute back pain is
      inferred from evidence in other acute pain conditions. Opioids do not seem to
      expedite return to work in injured workers or improve functional outcomes of
      acute back pain in primary care. For chronic back pain, systematic reviews find
      scant evidence of efficacy. Randomized controlled trials have high dropout rates,
      brief duration (four months or less), and highly selected patients. Opioids seem
      to have short term analgesic efficacy for chronic back pain, but benefits for
      function are less clear. The magnitude of pain relief across chronic non-cancer
      pain conditions is about 30%. Given the brevity of randomized controlled trials,
      the long term effectiveness and safety of opioids are unknown. Loss of long term
      efficacy could result from drug tolerance and emergence of hyperalgesia.
      Complications of opioid use include addiction and overdose related mortality,
      which have risen in parallel with prescription rates. Common short term side
      effects are constipation, nausea, sedation, and increased risk of falls and
      fractures. Longer term side effects may include depression and sexual
      dysfunction. Screening for high risk patients, treatment agreements, and urine
      testing have not reduced overall rates of opioid prescribing, misuse, or
      overdose. Newer strategies for reducing risks include more selective prescription
      of opioids and lower doses; use of prescription monitoring programs; avoidance of
      co-prescription with sedative hypnotics; and reformulations that make drugs more
      difficult to snort, smoke, or inject. 

PMID- 25561512
TI  - Role of positron emission tomography for the monitoring of response to therapy in
      breast cancer.
AB  - This review considers the potential utility of positron emission tomography (PET)
      tracers in the setting of response monitoring in breast cancer, with a special
      emphasis on glucose metabolic changes assessed with (18)F-fluorodeoxyglucose
      (FDG). In the neoadjuvant setting of breast cancer, the metabolic response can
      predict the final complete pathologic response after the first cycles of
      chemotherapy. Because tumor metabolic behavior highly depends on cancer subtype,
      studies are ongoing to define the optimal metabolic criteria of tumor response in
      each subtype. The recent multicentric randomized AVATAXHER trial has suggested,
      in the human epidermal growth factor 2-positive subtype, a clinical benefit of
      early tailoring the neoadjuvant treatment in women with poor metabolic response
      after the first course of treatment. In the bone-dominant metastatic setting,
      there is increasing clinical evidence that FDG-PET/computed tomography (CT) is
      the most accurate imaging modality for assessment of the tumor response to
      treatment when both metabolic information and morphologic information are
      considered. Nevertheless, there is a need to define standardized metabolic
      criteria of response, including the heterogeneity of response among metastases,
      and to evaluate the costs and health outcome of FDG-PET/CT compared with
      conventional imaging. New non-FDG radiotracers highlighting specific molecular
      hallmarks of breast cancer cells have recently emerged in preclinical and
      clinical studies. These biomarkers can take into account the heterogeneity of
      tumor biology in metastatic lesions. They may provide valuable clinical
      information for physicians to select and monitor the effectiveness of novel
      therapeutics targeting the same molecular pathways of breast tumor. 

PMID- 25561515
TI  - Electrocardiographic changes during exercise in acute hypoxia and susceptibility
      to severe high-altitude illnesses.
AB  - BACKGROUND: The goals of this study were to compare ECG at moderate exercise in
      normoxia and hypoxia at the same heart rate, to provide evidence of independent
      predictors of hypoxia-induced ECG changes, and to evaluate ECG risk factors of
      severe high-altitude illness. METHODS AND RESULTS: A total of 456 subjects
      performed a 20-minute hypoxia exercise test with continuous recording of ECG and
      physiological measurements before a sojourn above 4000 m. Hypoxia did not induce
      any conduction disorder, arrhythmias, or change in QRS axis. The amplitude of the
      P wave in V1 was lower in hypoxia than in normoxia. The amplitudes of the R, S,
      and T waves and the Sokolow index decreased in hypoxia. Under hypoxia, the
      amplitude of the ST segment decreased in II and V6 and increased in V1, the ST
      slope rose in V5 and V6, and the J point was lower in II, V5, and V6.
      Multivariate regression of hypoxic/normoxic ratios of electrophysiological
      parameters and clinical characteristics showed a correlation between the decrease
      in Sokolow index and T-wave amplitude in V5 with desaturation at exercise.
      Trained status and low body mass index were associated with a smaller decrease in
      T-wave amplitude in V5 and V6. Comparison of ECG between subjects suffering or
      not suffering from severe high-altitude illness failed to show any difference.
      CONCLUSIONS: During a hypoxia exercise test, a dose-dependent hypoxia-induced
      decrease in the amplitude of the P/QRS/T waves was observed. No standard ECG
      characteristic predicted the risk of developing severe high-altitude illness.
      Further studies are required to clarify the cause of these electric changes and
      their potential predictive role in cardiac events.

PMID- 25561514
TI  - Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac
      fatty acid uptake.
AB  - BACKGROUND: Microvascular endothelium in different organs is specialized to
      fulfill the particular needs of parenchymal cells. However, specific information
      about heart capillary endothelial cells (ECs) is lacking. METHODS AND RESULTS:
      Using microarray profiling on freshly isolated ECs from heart, brain, and liver,
      we revealed a genetic signature for microvascular heart ECs and identified
      Meox2/Tcf15 heterodimers as novel transcriptional determinants. This signature
      was largely shared with skeletal muscle and adipose tissue endothelium and was
      enriched in genes encoding fatty acid (FA) transport-related proteins. Using gain
      and loss-of-function approaches, we showed that Meox2/Tcf15 mediate FA uptake in
      heart ECs, in part, by driving endothelial CD36 and lipoprotein lipase expression
      and facilitate FA transport across heart ECs. Combined Meox2 and Tcf15
      haplodeficiency impaired FA uptake in heart ECs and reduced FA transfer to
      cardiomyocytes. In the long term, this combined haplodeficiency resulted in
      impaired cardiac contractility. CONCLUSIONS: Our findings highlight a regulatory
      role for ECs in FA transfer to the heart parenchyma and unveil 2 of its intrinsic
      regulators. Our insights could be used to develop new strategies based on
      endothelial Meox2/Tcf15 targeting to modulate FA transfer to the heart and remedy
      cardiac dysfunction resulting from altered energy substrate usage.

PMID- 25561517
TI  - Sarcopenia in COPD: prevalence, clinical correlates and response to pulmonary
      rehabilitation.
AB  - BACKGROUND: Age-related loss of muscle, sarcopenia, is recognised as a clinical
      syndrome with multiple contributing factors. International European Working Group
      on Sarcopenia in Older People (EWGSOP) criteria require generalised loss of
      muscle mass and reduced function to diagnose sarcopenia. Both are common in COPD
      but are usually studied in isolation and in the lower limbs. OBJECTIVES: To
      determine the prevalence of sarcopenia in COPD, its impact on function and health
      status, its relationship with quadriceps strength and its response to pulmonary
      rehabilitation (PR). METHODS: EWGSOP criteria were applied to 622 outpatients
      with stable COPD. Body composition, exercise capacity, functional performance,
      physical activity and health status were assessed. Using a case-control design,
      response to PR was determined in 43 patients with sarcopenia and a propensity
      score-matched non-sarcopenic group. RESULTS: Prevalence of sarcopenia was 14.5%
      (95% CI 11.8% to 17.4%), which increased with age and Global Initiative for
      Chronic Obstructive Pulmonary Disease (GOLD) stage, but did not differ by gender
      or the presence of quadriceps weakness (14.9 vs 13.8%, p=0.40). Patients with
      sarcopenia had reduced exercise capacity, functional performance, physical
      activity and health status compared with patients without sarcopenia (p<0.001),
      but responded similarly following PR; 12/43 patients were no longer classified as
      sarcopenic following PR. CONCLUSIONS: Sarcopenia affects 15% of patients with
      stable COPD and impairs function and health status. Sarcopenia does not impact on
      response to PR, which can lead to a reversal of the syndrome in select patients.

PMID- 25561516
TI  - Transparent reporting of a multivariable prediction model for individual
      prognosis or diagnosis (TRIPOD): the TRIPOD statement. The TRIPOD Group.
AB  - BACKGROUND: Prediction models are developed to aid health care providers in
      estimating the probability or risk that a specific disease or condition is
      present (diagnostic models) or that a specific event will occur in the future
      (prognostic models), to inform their decision making. However, the overwhelming
      evidence shows that the quality of reporting of prediction model studies is poor.
      Only with full and clear reporting of information on all aspects of a prediction
      model can risk of bias and potential usefulness of prediction models be
      adequately assessed. METHODS: The Transparent Reporting of a multivariable
      prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative
      developed a set of recommendations for the reporting of studies developing,
      validating, or updating a prediction model, whether for diagnostic or prognostic
      purposes. This article describes how the TRIPOD Statement was developed. An
      extensive list of items based on a review of the literature was created, which
      was reduced after a Web-based survey and revised during a 3-day meeting in June
      2011 with methodologists, health care professionals, and journal editors. The
      list was refined during several meetings of the steering group and in e-mail
      discussions with the wider group of TRIPOD contributors. RESULTS: The resulting
      TRIPOD Statement is a checklist of 22 items, deemed essential for transparent
      reporting of a prediction model study. The TRIPOD Statement aims to improve the
      transparency of the reporting of a prediction model study regardless of the study
      methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD
      explanation and elaboration document. CONCLUSIONS: To aid the editorial process
      and readers of prediction model studies, it is recommended that authors include a
      completed checklist in their submission (also available at www.tripod
      statement.org).

PMID- 25561518
TI  - Genome-wide discovery of human splicing branchpoints.
AB  - During the splicing reaction, the 5' intron end is joined to the branchpoint
      nucleotide, selecting the next exon to incorporate into the mature RNA and
      forming an intron lariat, which is excised. Despite a critical role in gene
      splicing, the locations and features of human splicing branchpoints are largely
      unknown. We use exoribonuclease digestion and targeted RNA-sequencing to enrich
      for sequences that traverse the lariat junction and, by split and inverted
      alignment, reveal the branchpoint. We identify 59,359 high-confidence human
      branchpoints in >10,000 genes, providing a first map of splicing branchpoints in
      the human genome. Branchpoints are predominantly adenosine, highly conserved, and
      closely distributed to the 3' splice site. Analysis of human branchpoints reveals
      numerous novel features, including distinct features of branchpoints for
      alternatively spliced exons and a family of conserved sequence motifs overlapping
      branchpoints we term B-boxes, which exhibit maximal nucleotide diversity while
      maintaining interactions with the keto-rich U2 snRNA. Different B-box motifs
      exhibit divergent usage in vertebrate lineages and associate with other splicing
      elements and distinct intron-exon architectures, suggesting integration within a
      broader regulatory splicing code. Lastly, although branchpoints are refractory to
      common mutational processes and genetic variation, mutations occurring at
      branchpoint nucleotides are enriched for disease associations. 

PMID- 25561519
TI  - BRF1 mutations alter RNA polymerase III-dependent transcription and cause
      neurodevelopmental anomalies.
AB  - RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to
      regulate protein synthesis. Dysregulation of Pol III transcription has been
      linked to cancer, and germline mutations in genes encoding Pol III subunits or
      tRNA processing factors cause neurogenetic disorders in humans, such as
      hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe
      an autosomal recessive disorder characterized by cerebellar hypoplasia and
      intellectual disability, as well as facial dysmorphic features, short stature,
      microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic
      missense alterations of BRF1 in three families. In support of the pathogenic
      potential of the discovered alleles, suppression or CRISPR-mediated deletion of
      brf1 in zebrafish embryos recapitulated key neurodevelopmental phenotypes; in
      vivo complementation showed all four candidate mutations to be pathogenic in an
      apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the
      transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We
      show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in
      Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce
      Pol III-related transcription activity in vitro. Taken together, our data show
      that BRF1 mutations that reduce protein activity cause neurodevelopmental
      anomalies, suggesting that BRF1-mediated Pol III transcription is required for
      normal cerebellar and cognitive development. 

PMID- 25561520
TI  - Independent role for presynaptic FMRP revealed by an FMR1 missense mutation
      associated with intellectual disability and seizures.
AB  - Fragile X syndrome (FXS) results in intellectual disability (ID) most often
      caused by silencing of the fragile X mental retardation 1 (FMR1) gene. The
      resulting absence of fragile X mental retardation protein 1 (FMRP) leads to both
      pre- and postsynaptic defects, yet whether the pre- and postsynaptic functions of
      FMRP are independent and have distinct roles in FXS neuropathology remain poorly
      understood. Here, we demonstrate an independent presynaptic function for FMRP
      through the study of an ID patient with an FMR1 missense mutation. This mutation,
      c.413G > A (R138Q), preserves FMRP's canonical functions in RNA binding and
      translational regulation, which are traditionally associated with postsynaptic
      compartments. However, neuronally driven expression of the mutant FMRP is unable
      to rescue structural defects at the neuromuscular junction in fragile x mental
      retardation 1 (dfmr1)-deficient Drosophila, suggesting a presynaptic-specific
      impairment. Furthermore, mutant FMRP loses the ability to rescue presynaptic
      action potential (AP) broadening in Fmr1 KO mice. The R138Q mutation also
      disrupts FMRP's interaction with the large-conductance calcium-activated
      potassium (BK) channels that modulate AP width. These results reveal a
      presynaptic- and translation-independent function of FMRP that is linked to a
      specific subset of FXS phenotypes. 

PMID- 25561521
TI  - Domains rearranged methyltransferase3 controls DNA methylation and regulates RNA
      polymerase V transcript abundance in Arabidopsis.
AB  - DNA methylation is a mechanism of epigenetic gene regulation and genome defense
      conserved in many eukaryotic organisms. In Arabidopsis, the DNA methyltransferase
      domains rearranged methylase 2 (DRM2) controls RNA-directed DNA methylation in a
      pathway that also involves the plant-specific RNA Polymerase V (Pol V).
      Additionally, the Arabidopsis genome encodes an evolutionarily conserved but
      catalytically inactive DNA methyltransferase, DRM3. Here, we show that DRM3 has
      moderate effects on global DNA methylation and small RNA abundance and that DRM3
      physically interacts with Pol V. In Arabidopsis drm3 mutants, we observe a lower
      level of Pol V-dependent noncoding RNA transcripts even though Pol V chromatin
      occupancy is increased at many sites in the genome. These findings suggest that
      DRM3 acts to promote Pol V transcriptional elongation or assist in the
      stabilization of Pol V transcripts. This work sheds further light on the
      mechanism by which long noncoding RNAs facilitate RNA-directed DNA methylation.

PMID- 25561522
TI  - Cdc45 (cell division cycle protein 45) guards the gate of the Eukaryote Replisome
      helicase stabilizing leading strand engagement.
AB  - DNA replication licensing is now understood to be the pathway that leads to the
      assembly of double hexamers of minichromosome maintenance (Mcm2-7) at origin
      sites. Cell division control protein 45 (Cdc45) and GINS proteins activate the
      latent Mcm2-7 helicase by inducing allosteric changes through binding, forming a
      Cdc45/Mcm2-7/GINS (CMG) complex that is competent to unwind duplex DNA. The CMG
      has an active gate between subunits Mcm2 and Mcm5 that opens and closes in
      response to nucleotide binding. The consequences of inappropriate Mcm2/5 gate
      actuation and the role of a side channel formed between GINS/Cdc45 and the outer
      edge of the Mcm2-7 ring for unwinding have remained unexplored. Here we uncover a
      novel function for Cdc45. Cross-linking studies trace the path of the DNA with
      the CMG complex at a fork junction between duplex and single strands with the
      bound CMG in an open or closed gate conformation. In the closed state, the
      lagging strand does not pass through the side channel, but in the open state, the
      leading strand surprisingly interacts with Cdc45. Mutations in the recombination
      protein J fold of Cdc45 that ablate this interaction diminish helicase activity.
      These data indicate that Cdc45 serves as a shield to guard against occasional
      slippage of the leading strand from the core channel. 

PMID- 25561523
TI  - Variation in Rapa Nui (Easter Island) land use indicates production and
      population peaks prior to European contact.
AB  - Many researchers believe that prehistoric Rapa Nui society collapsed because of
      centuries of unchecked population growth within a fragile environment. Recently,
      the notion of societal collapse has been questioned with the suggestion that
      extreme societal and demographic change occurred only after European contact in
      AD 1722. Establishing the veracity of demographic dynamics has been hindered by
      the lack of empirical evidence and the inability to establish a precise
      chronological framework. We use chronometric dates from hydrated obsidian
      artifacts recovered from habitation sites in regional study areas to evaluate
      regional land-use within Rapa Nui. The analysis suggests region-specific dynamics
      including precontact land use decline in some near-coastal and upland areas and
      postcontact increases and subsequent declines in other coastal locations. These
      temporal land-use patterns correlate with rainfall variation and soil quality,
      with poorer environmental locations declining earlier. This analysis confirms
      that the intensity of land use decreased substantially in some areas of the
      island before European contact. 

PMID- 25561526
TI  - Attenuation of sinking particulate organic carbon flux through the mesopelagic
      ocean.
AB  - The biological carbon pump, which transports particulate organic carbon (POC)
      from the surface to the deep ocean, plays an important role in regulating
      atmospheric carbon dioxide (CO2) concentrations. We know very little about
      geographical variability in the remineralization depth of this sinking material
      and less about what controls such variability. Here we present previously
      unpublished profiles of mesopelagic POC flux derived from neutrally buoyant
      sediment traps deployed in the North Atlantic, from which we calculate the
      remineralization length scale for each site. Combining these results with
      corresponding data from the North Pacific, we show that the observed variability
      in attenuation of vertical POC flux can largely be explained by temperature, with
      shallower remineralization occurring in warmer waters. This is seemingly
      inconsistent with conclusions drawn from earlier analyses of deep-sea sediment
      trap and export flux data, which suggest lowest transfer efficiency at high
      latitudes. However, the two patterns can be reconciled by considering relatively
      intense remineralization of a labile fraction of material in warm waters,
      followed by efficient downward transfer of the remaining refractory fraction,
      while in cold environments, a larger labile fraction undergoes slower
      remineralization that continues over a longer length scale. Based on the observed
      relationship, future increases in ocean temperature will likely lead to shallower
      remineralization of POC and hence reduced storage of CO2 by the ocean. 

PMID- 25561524
TI  - Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants.
AB  - Aging research has been very successful at identifying signaling pathways and
      evolutionarily conserved genes that extend lifespan with the assumption that an
      increase in lifespan will also increase healthspan. However, it is largely
      unknown whether we are extending the healthy time of life or simply prolonging a
      period of frailty with increased incidence of age-associated diseases. Here we
      use Caenorhabditis elegans, one of the premiere systems for lifespan studies, to
      determine whether lifespan and healthspan are intrinsically correlated. We
      conducted multiple cellular and organismal assays on wild type as well as four
      long-lived mutants (insulin/insulin-like growth factor-1, dietary restriction,
      protein translation, mitochondrial signaling) in a longitudinal manner to
      determine the health of the animals as they age. We find that some long-lived
      mutants performed better than wild type when measured chronologically (number of
      days). However, all long-lived mutants increased the proportion of time spent in
      a frail state. Together, these data suggest that lifespan can no longer be the
      sole parameter of interest and reveal the importance of evaluating multiple
      healthspan parameters for future studies on antiaging interventions. 

PMID- 25561525
TI  - Adaptive introgression in an African malaria mosquito coincident with the
      increased usage of insecticide-treated bed nets.
AB  - Animal species adapt to changes in their environment, including man-made changes
      such as the introduction of insecticides, through selection for advantageous
      genes already present in populations or newly arisen through mutation. A possible
      alternative mechanism is the acquisition of adaptive genes from related species
      via a process known as adaptive introgression. Differing levels of insecticide
      resistance between two African malaria vectors, Anopheles coluzzii and Anopheles
      gambiae, have been attributed to assortative mating between the two species. In a
      previous study, we reported two bouts of hybridization observed in the town of
      Selinkenyi, Mali in 2002 and 2006. These hybridization events did not appear to
      be directly associated with insecticide-resistance genes. We demonstrate that
      during a brief breakdown in assortative mating in 2006, A. coluzzii inherited the
      entire A. gambiae-associated 2L divergence island, which includes a suite of
      insecticide-resistance alleles. In this case, introgression was coincident with
      the start of a major insecticide-treated bed net distribution campaign in Mali.
      This suggests that insecticide exposure altered the fitness landscape, favoring
      the survival of A. coluzzii/A. gambiae hybrids, and provided selection pressure
      that swept the 2L divergence island through A. coluzzii populations in Mali. We
      propose that the work described herein presents a unique description of the
      temporal dynamics of adaptive introgression in an animal species and represents a
      mechanism for the rapid evolution of insecticide resistance in this important
      vector of human malaria in Africa. 

PMID- 25561527
TI  - Social status modulates prosocial behavior and egalitarianism in preschool
      children and adults.
AB  - Humans are a cooperative species, capable of altruism and the creation of shared
      norms that ensure fairness in society. However, individuals with different
      educational, cultural, economic, or ethnic backgrounds differ in their levels of
      social investment and endorsement of egalitarian values. We present four
      experiments showing that subtle cues to social status (i.e., prestige and
      reputation in the eyes of others) modulate prosocial orientation. The experiments
      found that individuals who experienced low status showed more communal and
      prosocial behavior, and endorsed more egalitarian life goals and values compared
      with those who experienced high status. Behavioral differences across high- and
      low-status positions appeared early in human ontogeny (4-5 y of age). 

PMID- 25561529
TI  - Crowd science user contribution patterns and their implications.
AB  - Scientific research performed with the involvement of the broader public (the
      crowd) attracts increasing attention from scientists and policy makers. A key
      premise is that project organizers may be able to draw on underused human
      resources to advance research at relatively low cost. Despite a growing number of
      examples, systematic research on the effort contributions volunteers are willing
      to make to crowd science projects is lacking. Analyzing data on seven different
      projects, we quantify the financial value volunteers can bring by comparing their
      unpaid contributions with counterfactual costs in traditional or online labor
      markets. The volume of total contributions is substantial, although some projects
      are much more successful in attracting effort than others. Moreover,
      contributions received by projects are very uneven across time--a tendency toward
      declining activity is interrupted by spikes typically resulting from outreach
      efforts or media attention. Analyzing user-level data, we find that most
      contributors participate only once and with little effort, leaving a relatively
      small share of users who return responsible for most of the work. Although top
      contributor status is earned primarily through higher levels of effort, top
      contributors also tend to work faster. This speed advantage develops over
      multiple sessions, suggesting that it reflects learning rather than inherent
      differences in skills. Our findings inform recent discussions about potential
      benefits from crowd science, suggest that involving the crowd may be more
      effective for some kinds of projects than others, provide guidance for project
      managers, and raise important questions for future research.

PMID- 25561528
TI  - Single cell-derived clonal analysis of human glioblastoma links functional and
      genomic heterogeneity.
AB  - Glioblastoma (GBM) is a cancer comprised of morphologically, genetically, and
      phenotypically diverse cells. However, an understanding of the functional
      significance of intratumoral heterogeneity is lacking. We devised a method to
      isolate and functionally profile tumorigenic clones from patient glioblastoma
      samples. Individual clones demonstrated unique proliferation and differentiation
      abilities. Importantly, naive patient tumors included clones that were
      temozolomide resistant, indicating that resistance to conventional GBM therapy
      can preexist in untreated tumors at a clonal level. Further, candidate therapies
      for resistant clones were detected with clone-specific drug screening. Genomic
      analyses revealed genes and pathways that associate with specific functional
      behavior of single clones. Our results suggest that functional clonal profiling
      used to identify tumorigenic and drug-resistant tumor clones will lead to the
      discovery of new GBM clone-specific treatment strategies. 

PMID- 25561530
TI  - Translatome analyses capture of opposing tissue-specific brassinosteroid signals
      orchestrating root meristem differentiation.
AB  - The mechanisms ensuring balanced growth remain a critical question in
      developmental biology. In plants, this balance relies on spatiotemporal
      integration of hormonal signaling pathways, but the understanding of the precise
      contribution of each hormone is just beginning to take form. Brassinosteroid (BR)
      hormone is shown here to have opposing effects on root meristem size, depending
      on its site of action. BR is demonstrated to both delay and promote onset of stem
      cell daughter differentiation, when acting in the outer tissue of the root
      meristem, the epidermis, and the innermost tissue, the stele, respectively. To
      understand the molecular basis of this phenomenon, a comprehensive spatiotemporal
      translatome mapping of Arabidopsis roots was performed. Analyses of wild type and
      mutants featuring different distributions of BR revealed autonomous, tissue
      specific gene responses to BR, implying its contrasting tissue-dependent impact
      on growth. BR-induced genes were primarily detected in epidermal cells of the
      basal meristem zone and were enriched by auxin-related genes. In contrast,
      repressed BR genes prevailed in the stele of the apical meristem zone.
      Furthermore, auxin was found to mediate the growth-promoting impact of BR
      signaling originating in the epidermis, whereas BR signaling in the stele
      buffered this effect. We propose that context-specific BR activity and responses
      are oppositely interpreted at the organ level, ensuring coherent growth. 

PMID- 25561531
TI  - Experimental replacement of an obligate insect symbiont.
AB  - Symbiosis, the close association of unrelated organisms, has been pivotal in
      biological diversification. In the obligate symbioses found in many insect hosts,
      organisms that were once independent are permanently and intimately associated,
      resulting in expanded ecological capabilities. The primary model for this kind of
      symbiosis is the association between the bacterium Buchnera and the pea aphid
      (Acyrthosiphon pisum). A longstanding obstacle to efforts to illuminate genetic
      changes underlying obligate symbioses has been the inability to experimentally
      disrupt and reconstitute symbiont-host partnerships. Our experiments show that
      Buchnera can be experimentally transferred between aphid matrilines and,
      furthermore, that Buchnera replacement has a massive effect on host fitness.
      Using a recipient pea aphid matriline containing Buchnera that are heat sensitive
      because of an allele eliminating the heat shock response of a small chaperone, we
      reduced native Buchnera through heat exposure and introduced a genetically
      distinct Buchnera from another matriline, achieving complete replacement and
      stable inheritance. This transfer disrupted 100 million years (~ 1 billion
      generations) of continuous maternal transmission of Buchnera in its host aphids.
      Furthermore, aphids with the Buchnera replacement enjoyed a dramatic increase in
      heat tolerance, directly demonstrating a strong effect of symbiont genotype on
      host ecology.

PMID- 25561532
TI  - Theory of point contact spectroscopy in correlated materials.
AB  - We developed a microscopic theory for the point-contact conductance between a
      metallic electrode and a strongly correlated material using the nonequilibrium
      Schwinger-Kadanoff-Baym-Keldysh formalism. We explicitly show that, in the
      classical limit, contact size shorter than the scattering length of the system,
      the microscopic model can be reduced to an effective model with transfer matrix
      elements that conserve in-plane momentum. We found that the conductance dI/dV is
      proportional to the effective density of states, that is, the integrated single
      particle spectral function A(omega = eV) over the whole Brillouin zone. From this
      conclusion, we are able to establish the conditions under which a non-Fermi
      liquid metal exhibits a zero-bias peak in the conductance. This finding is
      discussed in the context of recent point-contact spectroscopy on the iron
      pnictides and chalcogenides, which has exhibited a zero-bias conductance peak. 

PMID- 25561535
TI  - Finding long chains in kidney exchange using the traveling salesman problem.
AB  - As of May 2014 there were more than 100,000 patients on the waiting list for a
      kidney transplant from a deceased donor. Although the preferred treatment is a
      kidney transplant, every year there are fewer donors than new patients, so the
      wait for a transplant continues to grow. To address this shortage, kidney paired
      donation (KPD) programs allow patients with living but biologically incompatible
      donors to exchange donors through cycles or chains initiated by altruistic
      (nondirected) donors, thereby increasing the supply of kidneys in the system. In
      many KPD programs a centralized algorithm determines which exchanges will take
      place to maximize the total number of transplants performed. This optimization
      problem has proven challenging both in theory, because it is NP-hard, and in
      practice, because the algorithms previously used were unable to optimally search
      over all long chains. We give two new algorithms that use integer programming to
      optimally solve this problem, one of which is inspired by the techniques used to
      solve the traveling salesman problem. These algorithms provide the tools needed
      to find optimal solutions in practice. 

PMID- 25561534
TI  - Epigenetic transitions leading to heritable, RNA-mediated de novo silencing in
      Arabidopsis thaliana.
AB  - In plants, RNA-directed DNA methylation (RdDM), a mechanism where epigenetic
      modifiers are guided to target loci by small RNAs, plays a major role in
      silencing of transposable elements (TEs) to maintain genome integrity. So far,
      two RdDM pathways have been identified: RNA Polymerase IV (PolIV)-RdDM and RNA
      dependent RNA Polymerase 6 (RDR6)-RdDM. PolIV-RdDM involves a self-reinforcing
      feedback mechanism that maintains TE silencing, but cannot explain how epigenetic
      silencing is first initiated. A function of RDR6-RdDM is to reestablish
      epigenetic silencing of active TEs, but it is unknown if this pathway can induce
      DNA methylation at naive, non-TE loci. To investigate de novo establishment of
      RdDM, we have used virus-induced gene silencing (VIGS) of an active flowering
      Wageningen epiallele. Using genetic mutants we show that unlike PolIV-RdDM, but
      like RDR6-RdDM, establishment of VIGS-mediated RdDM requires PolV and DRM2 but
      not Dicer like-3 and other PolIV pathway components. DNA methylation in VIGS is
      likely initiated by a process guided by virus-derived small (s) RNAs that are
      21/22-nt in length and reinforced or maintained by 24-nt sRNAs. We demonstrate
      that VIGS-RdDM as a tool for gene silencing can be enhanced by use of mutant
      plants with increased production of 24-nt sRNAs to reinforce the level of RdDM.

PMID- 25561533
TI  - Enduring good memories of infant trauma: rescue of adult neurobehavioral deficits
      via amygdala serotonin and corticosterone interaction.
AB  - Children form a strong attachment to their caregiver--even when that caretaker is
      abusive. Paradoxically, despite the trauma experienced within this relationship,
      the child develops a preference for trauma-linked cues--a phenomenon known as
      trauma bonding. Although infant trauma compromises neurobehavioral development,
      the mechanisms underlying the interaction between infant trauma bonding (i.e.,
      learned preference for trauma cues) and the long-term effects of trauma (i.e.,
      depressive-like behavior, amygdala dysfunction) are unknown. We modeled infant
      trauma bonding by using odor-shock conditioning in rat pups, which engages the
      attachment system and produces a life-long preference for the odor that was
      paired with shock. In adulthood, this trauma-linked odor rescues depressive-like
      behavior and amygdala dysfunction, reduces corticosterone (CORT) levels, and
      exerts repair-related changes at the molecular level. Amygdala microarray after
      rescue implicates serotonin (5-HT) and glucocorticoids (GCs), and a causal role
      was verified through microinfusions. Blocking amygdala 5-HT eliminates the rescue
      effect; increasing amygdala 5-HT and blocking systemic CORT mimics it. Our
      findings suggest that infant trauma cues share properties with antidepressants
      and safety signals and provide insight into mechanisms by which infant trauma
      memories remain powerful throughout life.

PMID- 25561536
TI  - Fermi surface reconstruction and multiple quantum phase transitions in the
      antiferromagnet CeRhIn5.
AB  - Conventional, thermally driven continuous phase transitions are described by
      universal critical behavior that is independent of the specific microscopic
      details of a material. However, many current studies focus on materials that
      exhibit quantum-driven continuous phase transitions (quantum critical points, or
      QCPs) at absolute zero temperature. The classification of such QCPs and the
      question of whether they show universal behavior remain open issues. Here we
      report measurements of heat capacity and de Haas-van Alphen (dHvA) oscillations
      at low temperatures across a field-induced antiferromagnetic QCP (Bc0 ~ 50 T) in
      the heavy-fermion metal CeRhIn5. A sharp, magnetic-field-induced change in Fermi
      surface is detected both in the dHvA effect and Hall resistivity at B0* ~ 30 T,
      well inside the antiferromagnetic phase. Comparisons with band-structure
      calculations and properties of isostructural CeCoIn5 suggest that the Fermi
      surface change at B0* is associated with a localized-to-itinerant transition of
      the Ce-4f electrons in CeRhIn5. Taken in conjunction with pressure experiments,
      our results demonstrate that at least two distinct classes of QCP are observable
      in CeRhIn5, a significant step toward the derivation of a universal phase diagram
      for QCPs.

PMID- 25561537
TI  - Clofazimine shortens the duration of the first-line treatment regimen for
      experimental chemotherapy of tuberculosis.
AB  - A key drug for the treatment of leprosy, clofazimine has recently been associated
      with highly effective and significantly shortened regimens for the treatment of
      multidrug-resistant tuberculosis (TB). Consequently, we hypothesized that
      clofazimine may also shorten the duration of treatment for drug-susceptible TB.
      We conducted a controlled trial in the mouse model of TB chemotherapy comparing
      the activity of the 6-mo standard regimen for TB treatment, i.e., 2 mo of daily
      rifampin, isoniazid, pyrazinamide, and ethambutol followed by 4 mo of rifampin
      and isoniazid, with a 4-mo clofazimine-containing regimen: 2 mo of daily
      rifampin, isoniazid, pyrazinamide, and clofazimine followed by 2 mo of rifampin,
      isoniazid, and clofazimine. Treatment efficacy was assessed on the basis of
      Mycobacterium tuberculosis colony counts in the lungs and spleens during
      treatment and on the proportion of mice with culture-positive relapse 6 mo after
      treatment cessation. No additive effect of clofazimine was observed after the
      first week of treatment, but, by the second week of treatment, the colony counts
      were significantly lower in the clofazimine-treated mice than in the mice
      receiving the standard regimen. Lung culture conversion was obtained after 3 and
      5 mo in mice treated with the clofazimine-containing and standard regimens,
      respectively, and relapse-free cure was obtained after 3 and 6 mo of treatment
      with the clofazimine-containing and standard regimens, respectively. Thus,
      clofazimine is a promising anti-TB drug with the potential to shorten the
      duration of TB chemotherapy by at least half (3 mo vs. 6 mo) in the mouse model
      of TB. 

PMID- 25561538
TI  - Context-dependent categorical perception in a songbird.
AB  - Some of the psychological abilities that underlie human speech are shared with
      other species. One hallmark of speech is that linguistic context affects both how
      speech sounds are categorized into phonemes, and how different versions of
      phonemes are produced. We here confirm earlier findings that swamp sparrows
      categorically perceive the notes that constitute their learned songs and then
      investigate how categorical boundaries differ according to context. We clustered
      notes according to their acoustic structure, and found statistical evidence for
      clustering into 10 population-wide note types. Examining how three related types
      were perceived, we found, in both discrimination and labeling tests, that an
      "intermediate" note type is categorized with a "short" type when it occurs at the
      beginning of a song syllable, but with a "long" type at the end of a syllable. In
      sum, three produced note-type clusters appear to be underlain by two perceived
      categories. Thus, in birdsong, as in human speech, categorical perception is
      context-dependent, and as is the case for human phonology, there is a complex
      relationship between underlying categorical representations and surface forms.
      Our results therefore suggest that complex phonology can evolve even in the
      absence of rich linguistic components, like syntax and semantics. 

PMID- 25561539
TI  - Groundwater sapping as the cause of irreversible desertification of Hunshandake
      Sandy Lands, Inner Mongolia, northern China.
AB  - In the middle-to-late Holocene, Earth's monsoonal regions experienced
      catastrophic precipitation decreases that produced green to desert state shifts.
      Resulting hydrologic regime change negatively impacted water availability and
      Neolithic cultures. Whereas mid-Holocene drying is commonly attributed to slow
      insolation reduction and subsequent nonlinear vegetation-atmosphere feedbacks
      that produce threshold conditions, evidence of trigger events initiating state
      switching has remained elusive. Here we document a threshold event ca. 4,200
      years ago in the Hunshandake Sandy Lands of Inner Mongolia, northern China,
      associated with groundwater capture by the Xilamulun River. This process
      initiated a sudden and irreversible region-wide hydrologic event that exacerbated
      the desertification of the Hunshandake, resulting in post-Humid Period mass
      migration of northern China's Neolithic cultures. The Hunshandake remains arid
      and is unlikely, even with massive rehabilitation efforts, to revert back to
      green conditions. 

PMID- 25561540
TI  - Targeted ablation of cholinergic interneurons in the dorsolateral striatum
      produces behavioral manifestations of Tourette syndrome.
AB  - Gilles de la Tourette syndrome (TS) is characterized by tics, which are
      transiently worsened by stress, acute administration of dopaminergic drugs, and
      by subtle deficits in motor coordination and sensorimotor gating. It represents
      the most severe end of a spectrum of tic disorders that, in aggregate, affect ~
      5% of the population. Available treatments are frequently inadequate, and the
      pathophysiology is poorly understood. Postmortem studies have revealed a
      reduction in specific striatal interneurons, including the large cholinergic
      interneurons, in severe disease. We tested the hypothesis that this deficit is
      sufficient to produce aspects of the phenomenology of TS, using a strategy for
      targeted, specific cell ablation in mice. We achieved ~ 50% ablation of the
      cholinergic interneurons of the striatum, recapitulating the deficit observed in
      patients postmortem, without any effect on GABAergic markers or on parvalbumin
      expressing fast-spiking interneurons. Interneuron ablation in the dorsolateral
      striatum (DLS), corresponding roughly to the human putamen, led to tic-like
      stereotypies after either acute stress or d-amphetamine challenge; ablation in
      the dorsomedial striatum, in contrast, did not. DLS interneuron ablation also led
      to a deficit in coordination on the rotorod, but not to any abnormalities in
      prepulse inhibition, a measure of sensorimotor gating. These results support the
      causal sufficiency of cholinergic interneuron deficits in the DLS to produce
      some, but not all, of the characteristic symptoms of TS.

PMID- 25561541
TI  - Signature of consciousness in the dynamics of resting-state brain activity.
AB  - At rest, the brain is traversed by spontaneous functional connectivity patterns.
      Two hypotheses have been proposed for their origins: they may reflect a
      continuous stream of ongoing cognitive processes as well as random fluctuations
      shaped by a fixed anatomical connectivity matrix. Here we show that both sources
      contribute to the shaping of resting-state networks, yet with distinct
      contributions during consciousness and anesthesia. We measured dynamical
      functional connectivity with functional MRI during the resting state in awake and
      anesthetized monkeys. Under anesthesia, the more frequent functional connectivity
      patterns inherit the structure of anatomical connectivity, exhibit fewer small
      world properties, and lack negative correlations. Conversely, wakefulness is
      characterized by the sequential exploration of a richer repertoire of functional
      configurations, often dissimilar to anatomical structure, and comprising positive
      and negative correlations among brain regions. These results reconcile theories
      of consciousness with observations of long-range correlation in the anesthetized
      brain and show that a rich functional dynamics might constitute a signature of
      consciousness, with potential clinical implications for the detection of
      awareness in anesthesia and brain-lesioned patients. 

PMID- 25561542
TI  - Temperature-dependent innate defense against the common cold virus limits viral
      replication at warm temperature in mouse airway cells.
AB  - Most isolates of human rhinovirus, the common cold virus, replicate more robustly
      at the cool temperatures found in the nasal cavity (33-35  degrees C) than at
      core body temperature (37  degrees C). To gain insight into the mechanism of
      temperature-dependent growth, we compared the transcriptional response of primary
      mouse airway epithelial cells infected with rhinovirus at 33  degrees C vs. 37 
      degrees C. Mouse airway cells infected with mouse-adapted rhinovirus 1B exhibited
      a striking enrichment in expression of antiviral defense response genes at 37 
      degrees C relative to 33  degrees C, which correlated with significantly higher
      expression levels of type I and type III IFN genes and IFN-stimulated genes
      (ISGs) at 37  degrees C. Temperature-dependent IFN induction in response to
      rhinovirus was dependent on the MAVS protein, a key signaling adaptor of the RIG
      I-like receptors (RLRs). Stimulation of primary airway cells with the synthetic
      RLR ligand poly I:C led to greater IFN induction at 37  degrees C relative to 33 
      degrees C at early time points poststimulation and to a sustained increase in the
      induction of ISGs at 37  degrees C relative to 33  degrees C. Recombinant type I
      IFN also stimulated more robust induction of ISGs at 37  degrees C than at 33 
      degrees C. Genetic deficiency of MAVS or the type I IFN receptor in infected
      airway cells permitted higher levels of viral replication, particularly at 37 
      degrees C, and partially rescued the temperature-dependent growth phenotype.
      These findings demonstrate that in mouse airway cells, rhinovirus replicates
      preferentially at nasal cavity temperature due, in part, to a less efficient
      antiviral defense response of infected cells at cool temperature. 

PMID- 25561543
TI  - Acceleration of conduction velocity linked to clustering of nodal components
      precedes myelination.
AB  - High-density accumulation of voltage-gated sodium (Nav) channels at nodes of
      Ranvier ensures rapid saltatory conduction along myelinated axons. To gain
      insight into mechanisms of node assembly in the CNS, we focused on early steps of
      nodal protein clustering. We show in hippocampal cultures that prenodes (i.e.,
      clusters of Nav channels colocalizing with the scaffold protein ankyrinG and
      nodal cell adhesion molecules) are detected before myelin deposition along axons.
      These clusters can be induced on purified neurons by addition of oligodendroglial
      secreted factor(s), whereas ankyrinG silencing prevents their formation. The Nav
      isoforms Nav1.1, Nav1.2, and Nav1.6 are detected at prenodes, with Nav1.6
      progressively replacing Nav1.2 over time in hippocampal neurons cultured with
      oligodendrocytes and astrocytes. However, the oligodendrocyte-secreted factor(s)
      can induce the clustering of Nav1.1 and Nav1.2 but not of Nav1.6 on purified
      neurons. We observed that prenodes are restricted to GABAergic neurons, whereas
      clustering of nodal proteins only occurs concomitantly with myelin ensheathment
      on pyramidal neurons, implying separate mechanisms of assembly among different
      neuronal subpopulations. To address the functional significance of these early
      clusters, we used single-axon electrophysiological recordings in vitro and showed
      that prenode formation is sufficient to accelerate the speed of axonal conduction
      before myelination. Finally, we provide evidence that prenodal clusters are also
      detected in vivo before myelination, further strengthening their physiological
      relevance. 

PMID- 25561544
TI  - Control of stem cell self-renewal and differentiation by the heterochronic genes
      and the cellular asymmetry machinery in Caenorhabditis elegans.
AB  - Transitions between asymmetric (self-renewing) and symmetric (proliferative) cell
      divisions are robustly regulated in the context of normal development and tissue
      homeostasis. To genetically assess the regulation of these transitions, we used
      the postembryonic epithelial stem (seam) cell lineages of Caenorhabditis elegans.
      In these lineages, the timing of these transitions is regulated by the
      evolutionarily conserved heterochronic pathway, whereas cell division asymmetry
      is conferred by a pathway consisting of Wnt (Wingless) pathway components,
      including posterior pharynx defect (POP-1)/TCF, APC related/adenomatosis
      polyposis coli (APR-1)/APC, and LIT-1/NLK (loss of intestine/Nemo-like kinase).
      Here we explore the genetic regulatory mechanisms underlying stage-specific
      transitions between self-renewing and proliferative behavior in the seam cell
      lineages. We show that mutations of genes in the heterochronic developmental
      timing pathway, including lin-14 (lineage defect), lin-28, lin-46, and the lin-4
      and let-7 (lethal defects)-family microRNAs, affect the activity of LIT-1/POP-1
      cellular asymmetry machinery and APR-1 polarity during larval development.
      Surprisingly, heterochronic mutations that enhance LIT-1 activity in seam cells
      can simultaneously also enhance the opposing, POP-1 activity, suggesting a role
      in modulating the potency of the cellular polarizing activity of the LIT-1/POP-1
      system as development proceeds. These findings illuminate how the evolutionarily
      conserved cellular asymmetry machinery can be coupled to microRNA-regulated
      developmental pathways for robust regulation of stem cell maintenance and
      proliferation during the course of development. Such genetic interactions between
      developmental timing regulators and cell polarity regulators could underlie
      transitions between asymmetric and symmetric stem cell fates in other systems and
      could be deregulated in the context of developmental disorders and cancer. 

PMID- 25561545
TI  - K-Ras4A splice variant is widely expressed in cancer and uses a hybrid membrane
      targeting motif.
AB  - The two products of the KRAS locus, K-Ras4A and K-Ras4B, are encoded by
      alternative fourth exons and therefore, possess distinct membrane-targeting
      sequences. The common activating mutations occur in exons 1 or 2 and therefore,
      render both splice variants oncogenic. K-Ras4A has been understudied, because it
      has been considered a minor splice variant. By priming off of the splice
      junction, we developed a quantitative RT-PCR assay for K-Ras4A and K-Ras4B
      message capable of measuring absolute amounts of the two transcripts. We found
      that K-Ras4A was widely expressed in 30 of 30 human cancer cell lines and amounts
      equal to K-Ras4B in 17 human colorectal tumors. Using splice variant-specific
      antibodies, we detected K-Ras4A protein in several tumor cell lines at a level
      equal to or greater than that of K-Ras4B. In addition to the CAAX motif, the C
      terminus of K-Ras4A contains a site of palmitoylation as well as a bipartite
      polybasic region. Although both were required for maximal efficiency, each of
      these could independently deliver K-Ras4A to the plasma membrane. Thus, among
      four Ras proteins, K-Ras4A is unique in possessing a dual membrane-targeting
      motif. We also found that, unlike K-Ras4B, K-Ras4A does not bind to the cytosolic
      chaperone delta-subunit of cGMP phosphodiesterase type 6 (PDE6delta). We conclude
      that efforts to develop anti-K-Ras drugs that interfere with membrane trafficking
      will have to take into account the distinct modes of targeting of the two K-Ras
      splice variants. 

PMID- 25561547
TI  - Donald F. Steiner MD, 1930-2014: discoverer of proinsulin.

PMID- 25561546
TI  - Central role of SIAH inhibition in DCC-dependent cardioprotection provoked by
      netrin-1/NO.
AB  - Deleted in colorectal cancer (DCC), a large transmembrane receptor of netrin-1,
      is critical for mediating netrin-1's cardioprotective function. In the present
      study we investigated novel mechanisms underlying netrin-1-induced, rapid, and
      feed-forward up-regulation of DCC, which is believed to sustain nitric oxide (NO)
      production to potentiate cardioprotection. Intriguingly, NO markedly reduced
      expression of the E3 ubiquitin ligase seven in absentia homolog (SIAH) that is
      specific for regulation of protesome-dependent DCC degradation, resulting in
      accumulation of DCC. The two SIAH isoforms compensate for each other when one is
      repressed; inhibition of both SIAH1 and SIAH2 using combined siRNAs significantly
      reduced infarct size while improving cardiac function after ischemia/reperfusion
      injury of the heart. This effect was absent in DCC-deficient mice. Moreover, in
      vivo RNAi inhibition of SIAH1/2 further augmented netrin-1's cardioprotective
      function. In summary, these data identify a novel therapeutic target of SIAH in
      facilitating NO/netrin-1-dependent cardioprotection, using the DCC receptor.
      Combination of netrin-1 and SIAH RNAi may prove to be a substantially effective
      therapy for myocardial infarction. 

PMID- 25561549
TI  - Novel neural circuit mechanism for visual edge detection.
AB  - The primary visual cortex is organized in a way that assigns a specific
      collection of neurons the job of providing the rest of the brain with all of the
      information it needs about each small part of the image present on the retina:
      Neighboring patches of the visual cortex provide the information about
      neighboring patches of the visual world. Each one of these cortical patches-
      often identified as a "pinwheel"--contains thousands of neurons, and its
      corresponding image patch is centered on a particular location in the retina. For
      stimuli within their image patch, neurons respond selectively to lines or edges
      with a particular slope (orientation tuning) and to regions of the patch of
      different sizes (known as spatial frequency tuning). The same number of neurons
      is devoted to reporting each possible slope (orientation). For the cells that
      cover different-sized regions of their image patch, however, the number of
      neurons assigned depends strongly on their preferred region size. Only a few
      neurons report on large and small parts of the image patch, but many neurons
      report visual information from medium-sized areas. I show here that having
      different numbers of neurons responsible for image regions of different sizes
      actually carries out a computation: Edges in the image patch are extracted. I
      also explain how this edge-detection computation is done.

PMID- 25561548
TI  - Single-molecule tracking of small GTPase Rac1 uncovers spatial regulation of
      membrane translocation and mechanism for polarized signaling.
AB  - Polarized Rac1 signaling is a hallmark of many cellular functions, including cell
      adhesion, motility, and cell division. The two steps of Rac1 activation are its
      translocation to the plasma membrane and the exchange of nucleotide from GDP to
      GTP. It is, however, unclear whether these two processes are regulated
      independent of each other and what their respective roles are in polarization of
      Rac1 signaling. We designed a single-particle tracking (SPT) method to
      quantitatively analyze the kinetics of Rac1 membrane translocation in living
      cells. We found that the rate of Rac1 translocation was significantly elevated in
      protrusions during cell spreading on collagen. Furthermore, combining FRET sensor
      imaging with SPT measurements in the same cell, the recruitment of Rac1 was found
      to be polarized to an extent similar to that of the nucleotide exchange process.
      Statistical analysis of single-molecule trajectories and optogenetic manipulation
      of membrane lipids revealed that Rac1 membrane translocation precedes nucleotide
      exchange, and is governed primarily by interactions with phospholipids,
      particularly PI(3,4,5)P3, instead of protein factors. Overall, the study
      highlights the significance of membrane translocation in spatial Rac1 signaling,
      which is in addition to the traditional view focusing primarily on GEF
      distribution and exchange reaction. 

PMID- 25561551
TI  - Single-cell, real-time detection of oxidative stress induced in Escherichia coli
      by the antimicrobial peptide CM15.
AB  - Antibiotics target specific biochemical mechanisms in bacteria. In response to
      new drugs, pathogenic bacteria rapidly develop resistance. In contrast,
      antimicrobial peptides (AMPs) have retained broad spectrum antibacterial potency
      over millions of years. We present single-cell fluorescence assays that detect
      reactive oxygen species (ROS) in the Escherichia coli cytoplasm in real time.
      Within 30 s of permeabilization of the cytoplasmic membrane by the cationic AMP
      CM15 [combining residues 1-7 of cecropin A (from moth) with residues 2-9 of
      melittin (bee venom)], three fluorescence signals report oxidative stress in the
      cytoplasm, apparently involving O2 (-), H2O2, and *OH. Mechanistic studies
      indicate that active respiration is a prerequisite to the CM15-induced oxidative
      damage. In anaerobic conditions, signals from ROS are greatly diminished and the
      minimum inhibitory concentration increases 20-fold. Evidently the natural human
      AMP LL-37 also induces a burst of ROS. Oxidative stress may prove a significant
      bacteriostatic mechanism for a variety of cationic AMPs. If so, host organisms
      may use the local oxygen level to modulate AMP potency. 

PMID- 25561552
TI  - Atmospheric record in the Hadean Eon from multiple sulfur isotope measurements in
      Nuvvuagittuq Greenstone Belt (Nunavik, Quebec).
AB  - Mass-independent fractionation of sulfur isotopes (S-MIF) results from
      photochemical reactions involving short-wavelength UV light. The presence of
      these anomalies in Archean sediments [(4-2.5 billion years ago, (Ga)] implies
      that the early atmosphere was free of the appropriate UV absorbers, of which
      ozone is the most important in the modern atmosphere. Consequently, S-MIF is
      considered some of the strongest evidence for the lack of free atmospheric oxygen
      before 2.4 Ga. Although temporal variations in the S-MIF record are thought to
      depend on changes in the abundances of gas and aerosol species, our limited
      understanding of photochemical mechanisms complicates interpretation of the S-MIF
      record in terms of atmospheric composition. Multiple sulfur isotope compositions
      (delta(33)S, delta(34)S, and delta(36)S) of the >3.8 billion-year-old
      Nuvvuagittuq Greenstone Belt (Ungava peninsula) have been investigated to track
      the early origins of S-MIF. Anomalous S-isotope compositions (Delta(33)S up to
      +2.20/00) confirm a sedimentary origin of sulfide-bearing banded iron and silica
      rich formations. Sharp isotopic transitions across sedimentary/igneous
      lithological boundaries indicate that primary surficial S-isotope compositions
      have been preserved despite a complicated metamorphic history. Furthermore,
      Nuvvuagittuq metasediments recorded coupled variations in (33)S/(32)S,
      (34)S/(32)S, and (36)S/(32)S that are statistically indistinguishable from those
      identified several times later in the Archean. The recurrence of the same S
      isotope pattern at both ends of the Archean Eon is unexpected, given the complex
      atmospheric, geological, and biological pathways involved in producing and
      preserving this fractionation. It implies that, within 0.8 billion years of
      Earth's formation, a common mechanism for S-MIF production was established in the
      atmosphere. 

PMID- 25561550
TI  - Programmable motion of DNA origami mechanisms.
AB  - DNA origami enables the precise fabrication of nanoscale geometries. We
      demonstrate an approach to engineer complex and reversible motion of nanoscale
      DNA origami machine elements. We first design, fabricate, and characterize the
      mechanical behavior of flexible DNA origami rotational and linear joints that
      integrate stiff double-stranded DNA components and flexible single-stranded DNA
      components to constrain motion along a single degree of freedom and demonstrate
      the ability to tune the flexibility and range of motion. Multiple joints with
      simple 1D motion were then integrated into higher order mechanisms. One mechanism
      is a crank-slider that couples rotational and linear motion, and the other is a
      Bennett linkage that moves between a compacted bundle and an expanded frame
      configuration with a constrained 3D motion path. Finally, we demonstrate
      distributed actuation of the linkage using DNA input strands to achieve
      reversible conformational changes of the entire structure on ~ minute timescales.
      Our results demonstrate programmable motion of 2D and 3D DNA origami mechanisms
      constructed following a macroscopic machine design approach.

PMID- 25561553
TI  - Structure of FcgammaRI in complex with Fc reveals the importance of glycan
      recognition for high-affinity IgG binding.
AB  - Fc gamma receptor I (FcgammaRI) contributes to protective immunity against
      bacterial infections, but exacerbates certain autoimmune diseases. The sole high
      affinity IgG receptor, FcgammaRI plays a significant role in immunotherapy. To
      elucidate the molecular mechanism of its high-affinity IgG binding, we determined
      the crystal structure of the extracellular domains of human FcgammaRI in complex
      with the Fc domain of human IgG1. FcgammaRI binds to the Fc in a similar mode as
      the low-affinity FcgammaRII and FcgammaRIII receptors. In addition to many
      conserved contacts, FcgammaRI forms additional hydrogen bonds and salt bridges
      with the lower hinge region of Fc. Unique to the high-affinity receptor-Fc
      complex, however, is the conformation of the receptor D2 domain FG loop, which
      enables a charged KHR motif to interact with proximal carbohydrate units of the
      Fc glycans. Both the length and the charge of the FcgammaRI FG loop are well
      conserved among mammalian species. Ala and Glu mutations of the FG loop KHR
      residues showed significant contributions of His-174 and Arg-175 to antibody
      binding, and the loss of the FG loop-glycan interaction resulted in an ~ 20- to
      30-fold decrease in FcgammaRI affinity to all three subclasses of IgGs.
      Furthermore, deglycosylation of IgG1 resulted in a 40-fold loss in FcgammaRI
      binding, demonstrating involvement of the receptor FG loop in glycan recognition.
      These results highlight a unique glycan recognition in FcgammaRI function and
      open potential therapeutic avenues based on antibody glycan engineering or small
      molecular glycan mimics to target FcgammaRI for certain autoimmune diseases.

PMID- 25561554
TI  - Semilocal density functional obeying a strongly tightened bound for exchange.
AB  - Because of its useful accuracy and efficiency, density functional theory (DFT) is
      one of the most widely used electronic structure theories in physics, materials
      science, and chemistry. Only the exchange-correlation energy is unknown, and
      needs to be approximated in practice. Exact constraints provide useful
      information about this functional. The local spin-density approximation (LSDA)
      was the first constraint-based density functional. The Lieb-Oxford lower bound on
      the exchange-correlation energy for any density is another constraint that plays
      an important role in the development of generalized gradient approximations
      (GGAs) and meta-GGAs. Recently, a strongly and optimally tightened lower bound on
      the exchange energy was proved for one- and two-electron densities, and
      conjectured for all densities. In this article, we present a realistic "meta-GGA
      made very simple" (MGGA-MVS) for exchange that respects this optimal bound, which
      no previous beyond-LSDA approximation satisfies. This constraint might have been
      expected to worsen predicted thermochemical properties, but in fact they are
      improved over those of the Perdew-Burke-Ernzerhof GGA, which has nearly the same
      correlation part. MVS exchange is however radically different from that of other
      GGAs and meta-GGAs. Its exchange enhancement factor has a very strong dependence
      upon the orbital kinetic energy density, which permits accurate energies even
      with the drastically tightened bound. When this nonempirical MVS meta-GGA is
      hybridized with 25% of exact exchange, the resulting global hybrid gives
      excellent predictions for atomization energies, reaction barriers, and weak
      interactions of molecules. 

PMID- 25561555
TI  - VEGFR3 does not sustain retinal angiogenesis without VEGFR2.
AB  - Angiogenesis, the formation of new blood vessels, is regulated by vascular
      endothelial growth factors (VEGFs) and their receptors (VEGFRs). VEGFR2 is
      abundant in the tip cells of angiogenic sprouts, where VEGF/VEGFR2 functions
      upstream of the delta-like ligand 4 (DLL4)/Notch signal transduction pathway.
      VEGFR3 is expressed in all endothelia and is indispensable for angiogenesis
      during early embryonic development. In adults, VEGFR3 is expressed in angiogenic
      blood vessels and some fenestrated endothelia. VEGFR3 is abundant in endothelial
      tip cells, where it activates Notch signaling, facilitating the conversion of tip
      cells to stalk cells during the stabilization of vascular branches. Subsequently,
      Notch activation suppresses VEGFR3 expression in a negative feedback loop. Here
      we used conditional deletions and a Notch pathway inhibitor to investigate the
      cross-talk between VEGFR2, VEGFR3, and Notch in vivo. We show that postnatal
      angiogenesis requires VEGFR2 signaling also in the absence of Notch or VEGFR3,
      and that even small amounts of VEGFR2 are able to sustain angiogenesis to some
      extent. We found that VEGFR2 is required independently of VEGFR3 for endothelial
      DLL4 up-regulation and angiogenic sprouting, and for VEGFR3 functions in
      angiogenesis. In contrast, VEGFR2 deletion had no effect, whereas VEGFR3 was
      essential for postnatal lymphangiogenesis, and even for lymphatic vessel
      maintenance in adult skin. Knowledge of these interactions and the signaling
      functions of VEGFRs in blood vessels and lymphatic vessels is essential for the
      therapeutic manipulation of the vascular system, especially when considering
      multitargeted antiangiogenic treatments. 

PMID- 25561556
TI  - Intracellular Cl- as a signaling ion that potently regulates Na+/HCO3-
      transporters.
AB  - Cl(-) is a major anion in mammalian cells involved in transport processes that
      determines the intracellular activity of many ions and plasma membrane potential.
      Surprisingly, a role of intracellular Cl(-) (Cl(-) in) as a signaling ion has not
      been previously evaluated. Here we report that Cl(-) in functions as a regulator
      of cellular Na(+) and HCO3 (-) concentrations and transepithelial transport
      through modulating the activity of several electrogenic Na(+)-HCO3 (-)
      transporters. We describe the molecular mechanism(s) of this regulation by
      physiological Cl(-) in concentrations highlighting the role of GXXXP motifs in
      Cl(-) sensing. Regulation of the ubiquitous Na(+)-HCO3(-) co-transport (NBC)e1-B
      is mediated by two GXXXP-containing sites; regulation of NBCe2-C is dependent on
      a single GXXXP motif; and regulation of NBCe1-A depends on a cryptic GXXXP motif.
      In the basal state NBCe1-B is inhibited by high Cl(-) in interacting at a low
      affinity GXXXP-containing site. IP3 receptor binding protein released with IP3
      (IRBIT) activation of NBCe1-B unmasks a second high affinity Cl(-) in interacting
      GXXXP-dependent site. By contrast, NBCe2-C, which does not interact with IRBIT,
      has a single high affinity N-terminal GXXP-containing Cl(-) in interacting site.
      NBCe1-A is unaffected by Cl(-) in between 5 and 140 mM. However, deletion of
      NBCe1-A residues 29-41 unmasks a cryptic GXXXP-containing site homologous with
      the NBCe1-B low affinity site that is involved in inhibition of NBCe1-A by Cl(-)
      in. These findings reveal a cellular Cl(-) in sensing mechanism that plays an
      important role in the regulation of Na(+) and HCO3 (-) transport, with critical
      implications for the role of Cl(-) in cellular ion homeostasis and epithelial
      fluid and electrolyte secretion.

PMID- 25561557
TI  - Flies expand the repertoire of protein structures that bind ice.
AB  - An antifreeze protein (AFP) with no known homologs has been identified in Lake
      Ontario midges (Chironomidae). The midge AFP is expressed as a family of isoforms
      at low levels in adults, which emerge from fresh water in spring before the
      threat of freezing temperatures has passed. The 9.1-kDa major isoform derived
      from a preproprotein precursor is glycosylated and has a 10-residue tandem
      repeating sequence xxCxGxYCxG, with regularly spaced cysteines, glycines, and
      tyrosines comprising one-half its 79 residues. Modeling and molecular dynamics
      predict a tightly wound left-handed solenoid fold in which the cysteines form a
      disulfide core to brace each of the eight 10-residue coils. The solenoid is
      reinforced by intrachain hydrogen bonds, side-chain salt bridges, and a row of
      seven stacked tyrosines on the hydrophobic side that forms the putative ice
      binding site. A disulfide core is also a feature of the similar-sized beetle AFP
      that is a beta-helix with seven 12-residue coils and a comparable circular
      dichroism spectrum. The midge and beetle AFPs are not homologous and their ice
      binding sites are radically different, with the latter comprising two parallel
      arrays of outward-pointing threonines. However, their structural similarities is
      an amazing example of convergent evolution in different orders of insects to cope
      with change to a colder climate and provide confirmation about the physical
      features needed for a protein to bind ice. 

PMID- 25561560
TI  - A generation at risk: young investigators and the future of the biomedical
      workforce.
AB  - A number of distressing trends, including a decline in the share of key research
      grants going to younger scientists, as well as a steady rise in the age at which
      investigators receive their first funding, are now a decades-long feature of the
      US biomedical research workforce. Working committees have proposed
      recommendations, policy makers have implemented reforms, and yet the trajectory
      of our funding regime away from young scientists has only worsened. An
      investigation of some of the major factors and their geneses at play in
      explaining the increasing average age to first RO1 is presented. Recommendations
      related to funding, peer review, career paths, and the university-government
      partnership are provided. 

PMID- 25561558
TI  - A KIR B centromeric region present in Africans but not Europeans protects
      pregnant women from pre-eclampsia.
AB  - In sub-Saharan Africans, maternal mortality is unacceptably high, with >400
      deaths per 100,000 births compared with <10 deaths per 100,000 births in
      Europeans. One-third of the deaths are caused by pre-eclampsia, a syndrome
      arising from defective placentation. Controlling placentation are maternal
      natural killer (NK) cells that use killer-cell immunoglobulin-like receptor (KIR)
      to recognize the fetal HLA-C molecules on invading trophoblast. We analyzed
      genetic polymorphisms of maternal KIR and fetal HLA-C in 484 normal and 254 pre
      eclamptic pregnancies at Mulago Hospital, Kampala, Uganda. The combination of
      maternal KIR AA genotypes and fetal HLA-C alleles encoding the C2 epitope
      associates with pre-eclampsia [P = 0.0318, odds ratio (OR) = 1.49]. The KIR genes
      associated with protection are located in centromeric KIR B regions that are
      unique to sub-Saharan African populations and contain the KIR2DS5 and KIR2DL1
      genes (P = 0.0095, OR = 0.59). By contrast, telomeric KIR B genes protect
      Europeans against pre-eclampsia. Thus, different KIR B regions protect sub
      Saharan Africans and Europeans from pre-eclampsia, whereas in both populations,
      the KIR AA genotype is a risk factor for the syndrome. These results emphasize
      the importance of undertaking genetic studies of pregnancy disorders in African
      populations with the potential to provide biological insights not available from
      studies restricted to European populations. 

PMID- 25561559
TI  - Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and
      overcomes resistance to artemisinin.
AB  - Pharmaceutical monotherapies against human malaria have proven effective,
      although ephemeral, owing to the inevitable evolution of resistant parasites.
      Resistance to two or more drugs delivered in combination will evolve more slowly;
      hence combination therapies have become the preferred norm in the fight against
      malaria. At the forefront of these efforts has been the promotion of Artemisinin
      Combination Therapy, but despite these efforts, resistance to artemisinin has
      begun to emerge. In 2012, we demonstrated the efficacy of the whole plant (WP)-
      not a tea, not an infusion--as a malaria therapy and found it to be more
      effective than a comparable dose of pure artemisinin in a rodent malaria model.
      Here we show that WP overcomes existing resistance to pure artemisinin in the
      rodent malaria Plasmodium yoelii. Moreover, in a long-term artificial selection
      for resistance in Plasmodium chabaudi, we tested resilience of WP against drug
      resistance in comparison with pure artemisinin (AN). Stable resistance to WP was
      achieved three times more slowly than stable resistance to AN. WP treatment
      proved even more resilient than the double dose of AN. The resilience of WP may
      be attributable to the evolutionary refinement of the plant's secondary metabolic
      products into a redundant, multicomponent defense system. Efficacy and resilience
      of WP treatment against rodent malaria provides compelling reasons to further
      explore the role of nonpharmaceutical forms of AN to treat human malaria.

PMID- 25561561
TI  - Plant functional traits and the multidimensional nature of species coexistence.
AB  - Understanding the processes maintaining species diversity is a central problem in
      ecology, with implications for the conservation and management of ecosystems.
      Although biologists often assume that trait differences between competitors
      promote diversity, empirical evidence connecting functional traits to the niche
      differences that stabilize species coexistence is rare. Obtaining such evidence
      is critical because traits also underlie the average fitness differences driving
      competitive exclusion, and this complicates efforts to infer community dynamics
      from phenotypic patterns. We coupled field-parameterized mathematical models of
      competition between 102 pairs of annual plants with detailed sampling of leaf,
      seed, root, and whole-plant functional traits to relate phenotypic differences to
      stabilizing niche and average fitness differences. Single functional traits were
      often well correlated with average fitness differences between species,
      indicating that competitive dominance was associated with late phenology, deep
      rooting, and several other traits. In contrast, single functional traits were
      poorly correlated with the stabilizing niche differences that promote
      coexistence. Niche differences could only be described by combinations of traits,
      corresponding to differentiation between species in multiple ecological
      dimensions. In addition, several traits were associated with both fitness
      differences and stabilizing niche differences. These complex relationships
      between phenotypic differences and the dynamics of competing species argue
      against the simple use of single functional traits to infer community assembly
      processes but lay the groundwork for a theoretically justified trait-based
      community ecology. 

PMID- 25561562
TI  - Novel thiosemicarbazones regulate the signal transducer and activator of
      transcription 3 (STAT3) pathway: inhibition of constitutive and interleukin 6
      induced activation by iron depletion.
AB  - Pharmacologic manipulation of metal pools in tumor cells is a promising strategy
      for cancer treatment. Here, we reveal how the iron-binding ligands
      desferrioxamine (DFO), di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone
      (Dp44mT), and di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC)
      inhibit constitutive and interleukin 6-induced activation of signal transducer
      and activator of transcription 3 (STAT3) signaling, which promotes proliferation,
      survival, and metastasis of cancer cells. We demonstrate that DFO, Dp44mT, and
      DpC significantly decrease constitutive phosphorylation of the STAT3
      transcription factor at Tyr705 in the pancreatic cancer cell lines PANC-1 and
      MIAPaCa-2 as well as the prostate cancer cell line DU145. These compounds also
      significantly decrease the dimerized STAT3 levels, the binding of nuclear STAT3
      to its target DNA, and the expression of downstream targets of STAT3, including
      cyclin D1, c-myc, and Bcl-2. Examination of upstream mediators of STAT3 in
      response to these ligands has revealed that Dp44mT and DpC could significantly
      decrease activation of the nonreceptor tyrosine kinase Src and activation of cAbl
      in DU145 and MIAPaCa-2 cells. In contrast to the effects of Dp44mT, DpC, or DFO
      on inhibiting STAT3 activation, the negative control compound di-2-pyridylketone
      2-methyl-3-thiosemicarbazone, or the DFO:Fe complex, which cannot bind cellular
      iron, had no effect. This demonstrates the role of iron-binding in the activity
      observed. Immunohistochemical staining of PANC-1 tumor xenografts showed a marked
      decrease in STAT3 in the tumors of mice treated with Dp44mT or DpC compared with
      the vehicle. Collectively, these studies demonstrate suppression of STAT3
      activity by iron depletion in vitro and in vivo, and reveal insights into
      regulation of the critical oncogenic STAT3 pathway.

PMID- 25561563
TI  - Diagnosis of cutaneous leishmaniasis: why punch when you can scrape?
AB  - Cutaneous leishmaniasis (CL) has been introduced to the Leishmania under-endemic
      Lebanese population in an uncontrolled manner as a result of recent large-scale
      displacement of refugees from endemic Syria. Accordingly, a quick and reliable
      method to diagnose CL is essential. Matched punch biopsies and air-dried
      scrapings on 72 patients were obtained. Scrapings were collected in two forms:
      thick drop (N = 33) or thin smear (N = 39). Clinical information was recorded.
      Sections of punch biopsies and scrapings were stained and examined
      microscopically. Polymerase chain reaction (PCR) was performed on both scraping
      forms and biopsies. The diagnostic sensitivity of the tests performed revealed
      that microscopy in conjunction with PCR on punch biopsies was the most sensitive
      test (93%) overall. However, taken individually, microscopy and PCR yielded the
      highest sensitivities when performed on drop scrapings (63% and 85%,
      respectively), and not smear scrapings (38% and 56%, respectively) as compared
      with the punch biopsies (44% and 83%, respectively). Microscopic concordance for
      punch biopsies and drop scrapings was present in 25 of 33 cases. Concordance was
      predicted only by the high/low parasitic index (PI: 3.1 +/- 1.7 and 0.4 +/- 0.5,
      respectively; P < 0.05). Herein, we optimized a novel rapid method for reliable
      diagnosis of CL based on drop scrapings with good agreement with the gold
      standard punch biopsy technique. 

PMID- 25561564
TI  - Ebola policies that hinder epidemic response by limiting scientific discourse.
AB  - There is an unprecedented epidemic of Ebola virus disease (EVD) in west Africa.
      There has been a strong response from dedicated health professionals. However,
      there have also been irrational and fear-based responses that have contributed to
      misallocation of resources, stigma, and deincentivizing volunteers to combat
      Ebola at its source. Recently, the State of Louisiana Department of Health and
      Hospitals issued a ban on those coming from affected countries wishing to attend
      the annual meetings of American Society of Tropical Medicine and Hygiene and the
      American Public Health Association, both of which were held in New Orleans. We
      argue against such policies, question evidence and motivations, and discuss their
      practical and ethical implications in hampering effective responses to EVD by the
      scientific community. We aim to shed light on this issue and its implications for
      the future of public health interventions, reflect on the responsibility of
      health providers and professional societies as advocates for patients and the
      public health, and call for health professionals and societies to work to
      challenge inappropriate political responses to public health crises. 

PMID- 25561565
TI  - Surgical treatment of multiple hydatid cysts in the liver of a pediatric patient.
AB  - Multiple hydatid cysts in the liver rarely occur in the pediatric population.
      Here, we present the case of a 16-year-old girl who presented with six hydatid
      cysts in the liver. The cysts were surgically removed and all found to be
      infertile. Interestingly, the patient had post-operative eosinophilia. From this
      experience, we conclude that individualized treatment is necessary for patients
      with multiple hydatid cysts. 

PMID- 25561566
TI  - Naturally-acquired dengue virus infections do not reduce short-term survival of
      infected Aedes aegypti from Ho Chi Minh City, Vietnam.
AB  - Transmission of dengue virus (DENV) from mosquito to human is dependent upon the
      survival of the mosquito beyond the virus extrinsic incubation period. Previous
      studies report conflicting results of the effects of DENV on Aedes aegypti
      survival. Here, we describe the effect of DENV on the short-term survival (up to
      12 d) of 4,321 Ae. aegypti mosquitoes blood-fed on 150 NS1-positive dengue
      patients hospitalized in the Hospital for Tropical Diseases, Ho Chi Minh City,
      Vietnam. Mosquito survival was not different between cohorts that fed upon blood
      from which 0% of mosquitoes became DENV infected (N = 88 feeds), or 100% became
      infected (N = 116 feeds). Subgroup analysis also did not reveal serotype
      dependent differences in survival, nor a relationship between survival and human
      plasma viremia levels. These results suggest that DENV infection adds minimal
      cost to Ae. aegypti, an important finding when parameterizing the vector
      competence of this mosquito. 

PMID- 25561567
TI  - Larval habitats characterization and species composition of Anopheles mosquitoes
      in Tunisia, with particular attention to Anopheles maculipennis complex.
AB  - In Tunisia, malaria transmission has been interrupted since 1980. However, the
      growing number of imported cases and the persistence of putative vectors stress
      the need for additional studies to assess the risk of malaria resurgence in the
      country. In this context, our aim was to update entomological data concerning
      Anopheles mosquitoes in Tunisia. From May to October of 2012, mosquito larval
      specimens were captured in 60 breeding sites throughout the country and
      identified at the species level using morphological keys. Environmental
      parameters of the larval habitats were recorded. Specimens belonging to the An.
      maculipennis complex were further identified to sibling species by the ribosomal
      deoxyribonucleic acid (rDNA)-internal transcribed spacer 2 (ITS2) polymerase
      chain reaction (PCR) technique. In total, 647 Anopheles larvae were collected
      from 25 habitats. Four species, including An. labranchiae, An. multicolor, An.
      sergentii, and An. algeriensis, were morphologically identified. rDNA-ITS2 PCR
      confirmed that An. labranchiae is the sole member of the An. maculipennis complex
      in Tunisia. An. labranchiae was collected throughout northern and central
      Tunisia, and it was highly associated with rural habitat, clear water, and
      sunlight areas. Larvae of An. multicolor and An. sergentii existed separately or
      together and were collected in southern Tunisia in similar types of breeding
      places. 

PMID- 25561568
TI  - The year that Ebola virus took over west Africa: missed opportunities for
      prevention.

PMID- 25561569
TI  - Ebola: perspectives from a nurse and patient.

PMID- 25561570
TI  - Malaria PCR detection in Cambodian low-transmission settings: dried blood spots
      versus venous blood samples.
AB  - In the context of malaria elimination, novel strategies for detecting very low
      malaria parasite densities in asymptomatic individuals are needed. One of the
      major limitations of the malaria parasite detection methods is the volume of
      blood samples being analyzed. The objective of the study was to compare the
      diagnostic accuracy of a malaria polymerase chain reaction assay, from dried
      blood spots (DBS, 5 MUL) and different volumes of venous blood (50 MUL, 200 MUL,
      and 1 mL). The limit of detection of the polymerase chain reaction assay, using
      calibrated Plasmodium falciparum blood dilutions, showed that venous blood
      samples (50 MUL, 200 MUL, 1 mL) combined with Qiagen extraction methods gave a
      similar threshold of 100 parasites/mL, ~100-fold lower than 5 MUL DBS/Instagene
      method. On a set of 521 field samples, collected in two different transmission
      areas in northern Cambodia, no significant difference in the proportion of
      parasite carriers, regardless of the methods used was found. The 5 MUL DBS method
      missed 27% of the samples detected by the 1 mL venous blood method, but most of
      the missed parasites carriers were infected by Plasmodium vivax (84%). The
      remaining missed P. falciparum parasite carriers (N = 3) were only detected in
      high-transmission areas. 

PMID- 25561572
TI  - Physical demands and salivary immunoglobulin A responses of elite Australian
      rules football athletes to match play.
AB  - PURPOSE: To examine the response or pre- and postmatch salivary immunoglobulin A
      concentration ([s-IgA]) to Australian Football League (AFL) match play and
      investigate the acute and cumulative influence of player workload and postmatch
      [s-IgA] after repeated participation in AFL match play. METHODS: Eleven elite AFL
      athletes (21.8+/-2.4 y, 186.9+/-7.9 cm, 87.4+/-7.5 kg) were monitored throughout
      3 matches during the preseason that were separated by 7 d. Saliva samples were
      collected across each AFL match at 24 h and 1 h prematch and 1, 12, 36, and 60 h
      postmatch to determine [s-IgA]. Global positioning systems (GPS) with integrated
      triaxial accelerometers were used to determine total player workload during match
      play. Hypothesis testing was conducted for time-dependent changes in [s-IgA] and
      player load using a repeated-measures ANOVA. RESULTS: Player load during match 3
      (1266+/-124.6 AU) was significantly (P<.01) greater than in match 1 (1096+/-115.1
      AU) and match 2 (1082+/-90.4 AU). Across match 3, [s-IgA] was significantly
      (P<.01) suppressed at 2 postmatch measures (12 and 36 h) compared with prematch
      measures (24 and 1 h), which coincided with significantly (P<.01) elevated player
      load. CONCLUSION: The findings indicate that an increase in player load during
      AFL preseason match play resulted in compromised postmatch mucosal immunological
      function. Longitudinal assessment of AFL-match player load and mucosal
      immunological function across the first 60 h of recovery may augment monitoring
      and preparedness strategies for athletes.

PMID- 25561573
TI  - 99 years of Guillain-Barre syndrome: pathophysiological insights from
      neurophysiology.

PMID- 25561571
TI  - Deciphering preferential interactions within supramolecular protein complexes:
      the proteasome case.
AB  - In eukaryotic cells, intracellular protein breakdown is mainly performed by the
      ubiquitin-proteasome system. Proteasomes are supramolecular protein complexes
      formed by the association of multiple sub-complexes and interacting proteins.
      Therefore, they exhibit a very high heterogeneity whose function is still not
      well understood. Here, using a newly developed method based on the combination of
      affinity purification and protein correlation profiling associated with high
      resolution mass spectrometry, we comprehensively characterized proteasome
      heterogeneity and identified previously unknown preferential associations within
      proteasome sub-complexes. In particular, we showed for the first time that the
      two main proteasome subtypes, standard proteasome and immunoproteasome, interact
      with a different subset of important regulators. This trend was observed in very
      diverse human cell types and was confirmed by changing the relative proportions
      of both 20S proteasome forms using interferon-gamma. The new method developed
      here constitutes an innovative and powerful strategy that could be broadly
      applied for unraveling the dynamic and heterogeneous nature of other biologically
      relevant supramolecular protein complexes. 

PMID- 25561574
TI  - The wrong James Parkinson.

PMID- 25561576
TI  - Large N: a strategy for improving regional sport performance.
AB  - It has been hypothesized that large differences in maximal performance can arise
      between various geopolitical regions solely on the basis of differing numbers of
      participants in the target activity. While there is evidence in support of this
      hypothesis for a measure of intellectual performance, the same relationship has
      not been examined for a measure of physical performance. PURPOSE: To determine
      whether the number of participants is a predictor of the best athletic
      performance in a region. METHODS: The 2005-2010 USA Swimming Age Group Detail
      reports were used to determine the number of competitive swimmers participating
      in each age group for the 59 local swimming communities in the United States. The
      USA Swimming performance database provided 50-yd-freestyle times in each
      community for boys and girls for each age (6-19 y). Simple linear regression was
      used to examine the relationship between the outcome variable (fastest time) and
      the predictor variable (log of the number of swimmers) for each combination of
      age, sex, and calendar year. RESULTS: The log of the number of swimmers in a
      region was a significant predictor of the best performance in that region for all
      168 combinations of age, sex, and calendar year (P<.05) and explained, on
      average, 41%, and as much as 62%, of the variance in the fastest time.
      CONCLUSION: These findings have important implications for the development of
      regional sport strategic policy. Increasing the number of participants in the
      target activity appears a viable strategy for improving regional performance.

PMID- 25561575
TI  - Loop L1 governs the DNA-binding specificity and order for RecA-catalyzed
      reactions in homologous recombination and DNA repair.
AB  - In all organisms, RecA-family recombinases catalyze homologous joint formation in
      homologous genetic recombination, which is essential for genome stability and
      diversification. In homologous joint formation, ATP-bound RecA/Rad51-recombinases
      first bind single-stranded DNA at its primary site and then interact with double
      stranded DNA at another site. The underlying reason and the regulatory mechanism
      for this conserved binding order remain unknown. A comparison of the loop L1
      structures in a DNA-free RecA crystal that we originally determined and in the
      reported DNA-bound active RecA crystals suggested that the aspartate at position
      161 in loop L1 in DNA-free RecA prevented double-stranded, but not single
      stranded, DNA-binding to the primary site. This was confirmed by the effects of
      the Ala-replacement of Asp-161 (D161A), analyzed directly by gel-mobility shift
      assays and indirectly by DNA-dependent ATPase activity and SOS repressor
      cleavage. When RecA/Rad51-recombinases interact with double-stranded DNA before
      single-stranded DNA, homologous joint-formation is suppressed, likely by forming
      a dead-end product. We found that the D161A-replacement reduced this suppression,
      probably by allowing double-stranded DNA to bind preferentially and reversibly to
      the primary site. Thus, Asp-161 in the flexible loop L1 of wild-type RecA
      determines the preference for single-stranded DNA-binding to the primary site and
      regulates the DNA-binding order in RecA-catalyzed recombinase reactions. 

PMID- 25561577
TI  - Whole-body cryotherapy's enhancement of acute recovery of running performance in
      well-trained athletes.
AB  - PURPOSE: To examine the effects of a whole-body cryotherapy (WBC) protocol (3 min
      at -110 degrees C) on acute recovery and key variables of endurance performance
      during high-intensity intermittent exercise in a thermoneutral environment.
      METHODS: Eleven endurance athletes were tested twice in a randomized crossover
      design in which 5*5 min of high-intensity running (HIR) were followed by 1 h of
      passive rest at ~22 degrees C, including either 3 min of whole-body exposure to 
      110 degrees C (WBC) or a placebo intervention of 3 min walking (PBO). A ramp-test
      protocol was performed before HIR (R1) and after the 1-h recovery period (R2).
      Time to exhaustion (tlim) was measured along with alterations in oxygen content
      of the vastus lateralis (TSI), oxygen consumption (VO2), capillary blood lactate,
      heart rate (HR), and rating of perceived exertion (RPE) during submaximal and
      maximal running. RESULTS: The difference in tlim between R1 and R2 was lower in
      WBC than in PBO (P<.05, effect size d=1.13). During R2, TSI was higher in WBC
      during submaximal and maximal running (P<.01, d=0.68-1.01). In addition, VO2, HR,
      and RPE were lower at submaximal level of R2 after WBC than in PBO (P=.04 to
      <.01, d=0.23-0.83). CONCLUSION: WBC improves acute recovery during high-intensity
      intermittent exercise in thermoneutral conditions. The improvements might be
      induced by enhanced oxygenation of the working muscles, as well as a reduction in
      cardiovascular strain and increased work economy at submaximal intensities.

PMID- 25561578
TI  - APOL1 nephropathy: from gene to mechanisms of kidney injury.
AB  - The contribution of African ancestry to the risk of focal segmental
      glomerulosclerosis and chronic kidney disease has been partially explained by the
      recently described chromosome 22q variants in the gene apolipoprotein L1 (APOL1).
      The APOL1 variants appear at a high allele frequency in populations of West
      African ancestry as a result of apparent adaptive selection of the heterozygous
      state. Heterozygosity protects from infection with Trypanosoma brucei
      rhodesiense. This review will describe the role of the approaches in population
      genetics for the description of APOL1-associated nephropathies and draw
      inferences as to the biologic mechanisms from genetic epidemiology findings to
      date. Modifier loci can influence APOL1 risk for the development of kidney
      disease. 'Second hits', both viral and non-viral, may explain the discrepancy
      between the remarkably high odds ratios and the low lifetime risks of kidney
      disease in two allele carriers of APOL1 risk variants. Therapeutic strategies for
      APOL1-associated nephropathies will require the prevention and treatment of these
      'second hits' and the development of drugs to protect the APOL1 downstream renal
      injury pathways.

PMID- 25561579
TI  - Gender-specific activity demands experienced during semiprofessional basketball
      game play.
AB  - PURPOSE: To compare game activity demands between female and male
      semiprofessional basketball players. METHODS: Female (n=12) and male (n=12)
      semiprofessional basketball players were monitored across 3 competitive games.
      Time-motion-analysis procedures quantified player activity into predefined
      movement categories across backcourt (BC) and frontcourt (FC) positions. Activity
      frequencies, durations, and distances were calculated relative to live playing
      time (min). Work:rest ratios were also calculated using the video data. Game
      activity was compared between genders for each playing position and all players.
      RESULTS: Female players performed at greater running work-rates than male players
      (45.7+/-1.4 vs. 42.1+/-1.7 m/min, P=.05), while male players performed more
      dribbling than female players (2.5+/-0.3 vs. 3.0+/-0.2 s/min; 8.4+/-0.3 vs. 9.7+/
      0.7 m/min, P=.05). Positional analyses revealed that female BC players performed
      more low-intensity shuffling (P=.04) and jumping (P=.05), as well as longer
      (P=.04) jogging durations, than male BC players. Female FC players executed more
      upper-body activity (P=.03) and larger work:rest ratios (P<.001) than male FC
      players. No significant gender differences were observed in the overall
      intermittent demands, distance traveled, high-intensity shuffling activity, and
      sprinting requirements during game play. CONCLUSIONS: These findings indicate
      that gender-specific running and dribbling differences might exist in
      semiprofessional basketball. Furthermore, position-specific variations between
      female and male basketball players should be considered. These data may prove
      useful in the development of gender-specific conditioning plans relative to
      playing position in basketball.

PMID- 25561580
TI  - Self-report versus direct measurement for assessment of fluid intake during a
      70.3-mile triathlon.
AB  - PURPOSE: Self-report (SR) has been the primary method used to assess fluid intake
      during endurance events, but unfortunately, little is known about the validity of
      SR. The purpose of this study was to compare SR fluid intake with direct
      measurement (DM) during a 70.3-mile triathlon. METHODS: Fifty-three (42 men, 11
      women) individuals competing in a 70.3-mile triathlon participated in the study.
      On the 13.1-mile-run section of the triathlon, 11 research stations provided
      fluid in bottles filled with 163 mL of water or carbohydrate-electrolyte beverage
      (CEB). Participants submitted bottles 25 m past aid stations to be reweighed
      postrace. Participants also answered questions regarding fluid intake postrace.
      Bland-Altman plots and 95% limits of agreement were used to assess precision of
      the measures, while least-squares regression assessed linear agreement. RESULTS:
      SR intakes during the run ranged from 0-1793, 0-1837, and 0-2628 mL for water,
      CEB, and total fluid, with corresponding DM intakes of 0-1599, 0-1642, and 0-2250
      mL. DM and SR showed strong linear agreement for water, CEB, and total fluid
      (R2=.71, .80, and .80). Mean differences between the measures on the Bland-Altman
      plots were small (13-41 mL), but relatively large differences (+/-500 mL) between
      the measures were apparent for some participants. CONCLUSIONS: SR is the
      predominant methodology used in field studies assessing hydration, despite little
      to no data confirming its validity. The results herein suggest that fluid-intake
      assessment methodology should be chosen on a case-by-case basis and that caution
      should be used when interpreting data based on SR.

PMID- 25561583
TI  - Initial experience with the PulseRider for the treatment of bifurcation
      aneurysms: report of first three cases in the USA.
AB  - INTRODUCTION: The PulseRider is a novel device intended for use in the treatment
      of aneurysms arising at bifurcations. We present the initial results of the first
      three cases in the USA employing the PulseRider device. METHODS: Aneurysms
      intended to be treated with the PulseRider device at a single institution were
      identified prospectively. Aneurysms arising at either the carotid terminus or
      basilar apex that were relatively broad-necked were considered candidates for
      treatment with the novel device. RESULTS: Patients were pretreated with dual
      antiplatelet therapy. All cases were performed under general endotracheal
      anesthesia. An appropriately sized PulseRider device was deployed across the neck
      of the aneurysm. A microcatheter was then navigated over a 0.014 inch microwire
      through the device into the aneurysm. Complete occlusion of the aneurysm was
      achieved in all cases without intraprocedural complications. CONCLUSIONS: We have
      found in our early experience with the Pulse Rider device that its use is safe
      and effective as an adjunct in the treatment of bifurcation aneurysms arising at
      the basilar apex or carotid terminus. As such, it represents a useful addition to
      the armamentarium of the neuroendovascular specialist.

PMID- 25561584
TI  - An overview of clinical associate roles in the neurointerventional specialty.
AB  - Neurointerventionalists have long partnered with certain types of clinical
      associates to provide longitudinal care. This overview summarizes differences in
      education, background, roles, and scopes of practice of the various clinical
      associates (physician assistants, nurse practitioners, clinical nurse
      specialists, radiology practitioner assistants, radiologist assistants, and
      nursing care coordinators). Key differences and similarities are highlighted to
      alleviate confusion about the roles clinical associates can assume on a
      neurointerventional service. This overview is intended to guide practices as they
      consider broadening their clinical support teams. 

PMID- 25561585
TI  - Transradial access in acute ischemic stroke intervention.
AB  - OBJECTIVE: To describe the feasibility and safety of transradial access (TRA) in
      the interventional management of acute ischemic stroke (AIS). METHODS: A
      retrospective review of the local institutional AIS interventional databases of
      three tertiary academic centers was performed and the use of TRA identified.
      RESULTS: TRA was attempted in 15 (1.5%) of 1001 patients; it was used in 12 cases
      due to transfemoral access (TFA) failure and in 3 as the primary strategy. The
      mean age was 72.3+/-8.6 and 46% were male. Baseline National Institutes of Health
      Stroke Scale score was 19.5+/-8.7, two patients (14%) received intravenous tissue
      plasminogen activator, and mean time from last known normal to intra-arterial
      therapy was 17.0+/-20.1 h. Five patients had anterior circulation occlusive
      disease and 10 had vertebrobasilar occlusions. TRA was effective in allowing clot
      engagement in 13 of 15 cases: one patient had a hypoplastic radial artery that
      precluded sheath advancement and one had chronic innominate artery occlusion that
      could not be crossed. Mean time to switch from TFA to TRA was 1.9+/-1.3 h and the
      mean time from radial puncture to reperfusion was 2.2+/-1.0 h. Modified
      Thrombolysis In Cerebral Infarction 2b-3 reperfusion via TRA was achieved in 9 of
      15 patients (60%). No radial puncture site complications were noted. At 90 days,
      two patients (13%) had a good clinical outcome and seven (50%) had died.
      CONCLUSIONS: Failure of TFA in the endovascular treatment of AIS is uncommon but
      leads to unacceptable delays in reperfusion and poor outcomes. Standardization of
      benchmarks for access switch could serve as a guide for neurointerventionalists.
      TRA is a valid approach for the endovascular treatment of AIS.

PMID- 25561586
TI  - A platform for gastric cancer screening in low- and middle-income countries.
AB  - Gastric cancer is the second leading cause of cancer death worldwide and
      screening programs have had a significant impact on reducing mortality. The
      majority of cases occur in low- and middle-income countries (LMIC), where
      endoscopy resources are traditionally limited. In this paper, we introduce a
      platform designed to enable inexpensive gastric screening to take place in remote
      areas of LMIC. The system consists of a swallowable endoscopic capsule connected
      to an external water distribution system by a multichannel soft tether.
      Pressurized water is ejected from the capsule to orient the view of the
      endoscopic camera. After completion of a cancer screening procedure, the outer
      shell of the capsule and the soft tether can be disposed, while the endoscopic
      camera is reclaimed without needing further reprocessing. The capsule, measuring
      12 mm in diameter and 28 mm in length, is able to visualize the inside of the
      gastric cavity by combining waterjet actuation and the adjustment of the tether
      length. Experimental assessment was accomplished through a set of bench trials,
      ex vivo analysis, and in vivo feasibility validation. During the ex vivo trials,
      the platform was able to visualize the main landmarks that are typically observed
      during a gastric cancer screening procedure in less than 8 min. Given the compact
      footprint, the minimal cost of the disposable parts, and the possibility of
      running on relatively available and inexpensive resources, the proposed platform
      can potentially widen gastric cancer screening programs in LMIC. 

PMID- 25561587
TI  - Spatial Coherence Profiles of Ictal High-Frequency Oscillations Correspond to
      Those of Interictal Low-Frequency Oscillations in the ECoG of Epileptic Patients.
AB  - GOAL: We have previously demonstrated that the coherence of high-frequency
      oscillations (HFOs; 80-300 Hz) increased during extratemporal lobe seizures in a
      consistent and spatially focused electrode cluster. In this study, we have
      investigated the relationship between cohered HFO intracranial EEG (iEEG)
      activity with that of slower low-frequency oscillations (LFOs; <80 Hz). METHODS:
      We applied wavelet phase coherence analysis to the iEEGs of patients with
      intractable extratemporal lobe epilepsy (ETLE). RESULTS: It was observed that
      areas on the implanted patient subdural grids, which exhibited strong ictal HFO
      coherence were similar to tissue regions displaying strong interictal LFO
      coherence in the 5-12 Hz frequency range, relative to all other electrodes. A
      positive surgical outcome was correlated with having the clinically marked
      seizure onset zone(s) in close proximity to HFO/LFO coherence highlighted regions
      of interest (ROIs). CONCLUSION: Recent studies have suggested that LFOs (in the 8
      12 Hz frequency range) play an important role in controlling cortical
      excitability, by exerting an inhibitory effect on cortical processing, and that
      the presence of strong theta activity (4-8 Hz) in awake adults is suggestive of
      abnormal and/or pathological activity. We speculate that the overlapping spatial
      regions exhibiting increased coherence in both ictal HFOs and interictal LFOs
      identified local abnormalities that underlie epileptogenic networks.
      SIGNIFICANCE: Whereas it is worthwhile to note that the small patient group ( n =
      7) studied here, somewhat limits the clinical significance of our study, the
      results presented here suggest targeting HFO activity in the 80-300 Hz frequency
      range and/or interictal LFO activity in the 5-12 Hz frequency range, when
      defining seizure-related ROIs in the iEEGs of patients with ETLE.

PMID- 25561588
TI  - Rapid model identification for online subcutaneous glucose concentration
      prediction for new subjects with type I diabetes.
AB  - GOAL: For conventional modeling methods, the work of model identification has to
      be repeated with sufficient data for each subject because different subjects may
      have different response to exogenous inputs. This may cause repetitive cost and
      burden for patients and clinicians and require a lot of modeling efforts. Here,
      to overcome the aforementioned problems, a rapid model development strategy for
      new subjects is proposed using the idea of model migration for online glucose
      prediction. METHODS: First, a base model is obtained that can be empirically
      identified from any subject or constructed by a priori knowledge. Then,
      parameters of inputs in the base model are properly revised based on a small
      amount of new data from new subjects so that the updated models can reflect the
      specific glucose dynamics excited by inputs for new subjects. These problems are
      investigated by developing autoregressive models with exogenous inputs (ARX)
      based on 30 in silico subjects using UVA/Padova metabolic simulator. RESULTS: The
      prediction accuracy of the rapid modeling method is comparable to that for
      subject-dependent modeling method for some cases. Also, it can present better
      generalization ability. CONCLUSION: The proposed method can be regarded as an
      effective and economic modeling method instead of repetitive subject-dependent
      modeling method especially for lack of modeling data.

PMID- 25561589
TI  - A novel system identification technique for improved wearable hemodynamics
      assessment.
AB  - Recent advances have led to renewed interest in ballistocardiography (BCG), a
      noninvasive measure of the small movements of the body due to cardiovascular
      events. A broad range of platforms have been developed and verified for BCG
      measurement including beds, chairs, and weighing scales: while the body is
      coupled to such a platform, the cardiogenic movements are measured. Wearable BCG,
      measured with an accelerometer affixed to the body, may enable continuous, or
      more regular, monitoring during the day; however, the signals from such wearable
      BCGs represent local or distal accelerations of skin and tissue rather than the
      whole body. In this paper, we propose a novel method to reconstruct the BCG
      measured with a weighing scale (WS BCG) from a wearable sensor via a training
      step to remove these local effects. Preliminary validation of this method was
      performed with 15 subjects: the wearable sensor was placed at three locations on
      the surface of the body while WS BCG measurements were recorded simultaneously. A
      regularized system identification approach was used to reconstruct the WS BCG
      from the wearable BCG. Preliminary results suggest that the relationship between
      local and central disturbances is highly dependent on both the individual and the
      location where the accelerometer is placed on the body and that these differences
      can be resolved via calibration to accurately measure changes in cardiac output
      and contractility from a wearable sensor. Such measurements could be highly
      effective, for example, for improved monitoring of heart failure patients at
      home. 

PMID- 25561590
TI  - A Predictive Model of Vertebral Trabecular Anisotropy From Ex Vivo Micro-CT.
AB  - Spine-related disorders are amongst the most frequently encountered problems in
      clinical medicine. For several applications such as 1) to improve the assessment
      of the strength of the spine, as well as 2) to optimize the personalization of
      spinal interventions, image-based biomechanical modeling of the vertebrae is
      expected to play an important predictive role. However, this requires the
      construction of computational models that are subject-specific and comprehensive.
      In particular, they need to incorporate information about the vertebral
      anisotropic micro-architecture, which plays a central role in the biomechanical
      function of the vertebrae. In practice, however, accurate personalization of the
      vertebral trabeculae has proven to be difficult as its imaging in vivo is
      currently infeasible. Consequently, this paper presents a statistical approach
      for accurate prediction of the vertebral fabric tensors based on a training
      sample of ex vivo micro-CT images. To the best of our knowledge, this is the
      first predictive model proposed and validated for vertebral datasets. The method
      combines features selection and partial least squares regression in order to
      derive optimal latent variables for the prediction of the fabric tensors based on
      the more easily extracted shape and density information. Detailed validation with
      20 ex vivo T12 vertebrae demonstrates the accuracy and consistency of the
      approach for the personalization of trabecular anisotropy. 

PMID- 25561592
TI  - A new multivariate statistical model for change detection in images acquired by
      homogeneous and heterogeneous sensors.
AB  - Remote sensing images are commonly used to monitor the earth surface evolution.
      This surveillance can be conducted by detecting changes between images acquired
      at different times and possibly by different kinds of sensors. A representative
      case is when an optical image of a given area is available and a new image is
      acquired in an emergency situation (resulting from a natural disaster for
      instance) by a radar satellite. In such a case, images with heterogeneous
      properties have to be compared for change detection. This paper proposes a new
      approach for similarity measurement between images acquired by heterogeneous
      sensors. The approach exploits the considered sensor physical properties and
      specially the associated measurement noise models and local joint distributions.
      These properties are inferred through manifold learning. The resulting similarity
      measure has been successfully applied to detect changes between many kinds of
      images, including pairs of optical images and pairs of optical-radar images.

PMID- 25561591
TI  - 3-D Adaptive Sparsity Based Image Compression With Applications to Optical
      Coherence Tomography.
AB  - We present a novel general-purpose compression method for tomographic images,
      termed 3D adaptive sparse representation based compression (3D-ASRC). In this
      paper, we focus on applications of 3D-ASRC for the compression of ophthalmic 3D
      optical coherence tomography (OCT) images. The 3D-ASRC algorithm exploits
      correlations among adjacent OCT images to improve compression performance, yet is
      sensitive to preserving their differences. Due to the inherent denoising
      mechanism of the sparsity based 3D-ASRC, the quality of the compressed images are
      often better than the raw images they are based on. Experiments on clinical-grade
      retinal OCT images demonstrate the superiority of the proposed 3D-ASRC over other
      well-known compression methods. 

PMID- 25561593
TI  - A multiscale wavelet-based test for isotropy of random fields on a regular
      lattice.
AB  - A test for isotropy of images modeled as stationary or intrinsically stationary
      random fields on a lattice is developed. The test is based on the wavelet theory,
      and can operate on the horizontal and vertical scale of choice, or on any
      combination of scales. Scale is introduced through the wavelet variances
      (sometimes called as the wavelet power spectrum), which decompose the variance
      over different horizontal and vertical spatial scales. The method is more general
      than existing tests for isotropy, since it handles intrinsically stationary
      random fields as well as second-order stationary fields. The performance of the
      method is demonstrated on samples from different random fields, and compared with
      three existing methods. It is competitive with or outperforms existing methods
      since it consistently rejects close to the nominal level for isotropic fields
      while having a rejection rate for anisotropic fields comparable with the existing
      methods in the stationary case, and superior in the intrinsic case. As practical
      examples, paper density images of handsheets and mammogram images are analyzed. 

PMID- 25561594
TI  - Low-complexity topological derivative-based segmentation.
AB  - Topological derivative has been employed for image segmentation and restoration.
      The topological derivative-based segmentation uses two sparse matrices, and the
      computational complexity of the segmentation grows up dramatically as the image
      size increases due to the size of the sparse matrix. Therefore, to provide a fast
      and accurate segmentation with low complexity, an effective scheme is proposed
      with keeping the same segmentation performance. To further reduce the
      computational complexity, the parallel processing structure for the proposed
      scheme is designed and implemented on graphics processing unit (GPU). In
      particular, to reduce the computational cost of generating and multiplying sparse
      matrices that are squared symmetric, the 2D filters consisting of the
      coefficients at nonborder regions of sparse matrices are defined, and the
      multiplication is converted into a convolution filtering. In addition, to design
      a parallel processing for the segmentation with the proposed scheme on a GPU, an
      image is divided into several blocks and they are processed in parallel.
      Experimental results show that the proposed scheme for topological derivative
      based segmentation reduces the computational complexity ~ 908 times, and the
      complexity of the proposed scheme is reduced ~ 17 times more from the parallel
      structure. In particular, the higher efficiency can be obtained from large sized
      images because the complexity of the proposed scheme does not depend on the image
      size. Moreover, the proposed scheme can provide almost identical segmentation
      result with the original sparse matrix-based approach. Therefore, we believe that
      the proposed scheme can be a useful tool for efficient topological derivative
      based segmentation.

PMID- 25561596
TI  - Accurate and robust line segment extraction using minimum entropy with Hough
      transform.
AB  - The Hough transform is a popular technique used in the field of image processing
      and computer vision. With a Hough transform technique, not only the normal angle
      and distance of a line but also the line-segment's length and midpoint (centroid)
      can be extracted by analysing the voting distribution around a peak in the Hough
      space. In this paper, a method based on minimum-entropy analysis is proposed to
      extract the set of parameters of a line segment. In each column around a peak in
      Hough space, the voting values specify probabilistic distributions. The
      corresponding entropies and statistical means are computed. The line-segment's
      normal angle and length are simultaneously computed by fitting a quadratic
      polynomial curve to the voting entropies. The line-segment's midpoint and normal
      distance are computed by fitting and interpolating a linear curve to the voting
      means. The proposed method is tested on simulated images for detection accuracy
      by providing comparative results. Experimental results on real-world images
      verify the method as well. The proposed method for line-segment detection is both
      accurate and robust in the presence of quantization error, background noise, or
      pixel disturbances.

PMID- 25561595
TI  - Multimodal registration via mutual information incorporating geometric and
      spatial context.
AB  - Multimodal image registration is a class of algorithms to find correspondence
      from different modalities. Since different modalities do not exhibit the same
      characteristics, finding accurate correspondence still remains a challenge. To
      deal with this, mutual information (MI)-based registration has been a preferred
      choice as MI is based on the statistical relationship between both volumes to be
      registered. However, MI has some limitations. First, MI-based registration often
      fails when there are local intensity variations in the volumes. Second, MI only
      considers the statistical intensity relationships between both volumes and
      ignores the spatial and geometric information about the voxel. In this work, we
      propose to address these limitations by incorporating spatial and geometric
      information via a 3D Harris operator. In particular, we focus on the registration
      between a high-resolution image and a low-resolution image. The MI cost function
      is computed in the regions where there are large spatial variations such as
      corner or edge. In addition, the MI cost function is augmented with geometric
      information derived from the 3D Harris operator applied to the high-resolution
      image. The robustness and accuracy of the proposed method were demonstrated using
      experiments on synthetic and clinical data including the brain and the tongue.
      The proposed method provided accurate registration and yielded better performance
      over standard registration methods.

PMID- 25561597
TI  - Online Sequential Extreme Learning Machine With Kernels.
AB  - The extreme learning machine (ELM) was recently proposed as a unifying framework
      for different families of learning algorithms. The classical ELM model consists
      of a linear combination of a fixed number of nonlinear expansions of the input
      vector. Learning in ELM is hence equivalent to finding the optimal weights that
      minimize the error on a dataset. The update works in batch mode, either with
      explicit feature mappings or with implicit mappings defined by kernels. Although
      an online version has been proposed for the former, no work has been done up to
      this point for the latter, and whether an efficient learning algorithm for online
      kernel-based ELM exists remains an open problem. By explicating some connections
      between nonlinear adaptive filtering and ELM theory, in this brief, we present an
      algorithm for this task. In particular, we propose a straightforward extension of
      the well-known kernel recursive least-squares, belonging to the kernel adaptive
      filtering (KAF) family, to the ELM framework. We call the resulting algorithm the
      kernel online sequential ELM (KOS-ELM). Moreover, we consider two different
      criteria used in the KAF field to obtain sparse filters and extend them to our
      context. We show that KOS-ELM, with their integration, can result in a highly
      efficient algorithm, both in terms of obtained generalization error and training
      time. Empirical evaluations demonstrate interesting results on some benchmarking
      datasets. 

PMID- 25561598
TI  - Pixel-Level Tissue Classification for Ultrasound Images.
AB  - BACKGROUND: Pixel-level tissue classification for ultrasound images, commonly
      applied to carotid images, is usually based on defining thresholds for the
      isolated pixel values. Ranges of pixel values are defined for the classification
      of each tissue. The classification of pixels is then used to determine the
      carotid plaque composition and, consequently, to determine the risk of diseases
      (e.g., strokes) and whether or not a surgery is necessary. The use of threshold
      based methods dates from the early 2000s but it is still widely used for virtual
      histology. METHODOLOGY/PRINCIPAL FINDINGS: We propose the use of descriptors that
      take into account information about a neighborhood of a pixel when classifying
      it. We evaluated experimentally different descriptors (statistical moments,
      texture-based, gradient-based, local binary patterns, etc.) on a dataset of five
      types of tissues: blood, lipids, muscle, fibrous, and calcium. The pipeline of
      the proposed classification method is based on image normalization, multiscale
      feature extraction, including the proposal of a new descriptor, and machine
      learning classification. We have also analyzed the correlation between the
      proposed pixel classification method in the ultrasound images and the real
      histology with the aid of medical specialists. CONCLUSIONS/SIGNIFICANCE: The
      classification accuracy obtained by the proposed method with the novel descriptor
      in the ultrasound tissue images (around 73%) is significantly above the accuracy
      of the state-of-the-art threshold-based methods (around 54%). The results are
      validated by statistical tests. The correlation between the virtual and real
      histology confirms the quality of the proposed approach showing it is a robust
      ally for the virtual histology in ultrasound images.

PMID- 25561599
TI  - Cross-Examination for Angle-Closure Glaucoma Feature Detection.
AB  - Effective feature selection plays a vital role in anterior segment imaging for
      determining the mechanism involved in angle-closure glaucoma (ACG) diagnosis.
      This research focuses on the use of redundant features for complex disease
      diagnosis such as ACG using anterior segment optical coherence tomography images.
      Both supervised [minimum redundancy maximum relevance (MRMR)] and unsupervised
      [Laplacian score (L-score)] feature selection algorithms have been cross-examined
      with different ACG mechanisms. An AdaBoost machine learning classifier is then
      used for classifying the five various classes of ACG mechanism such as iris roll,
      lens, pupil block, plateau iris, and no mechanism using both feature selection
      methods. The overall accuracy has shown that the usefulness of redundant features
      by L-score method in improved ACG diagnosis compared to minimum redundant
      features by MRMR method. 

PMID- 25561600
TI  - Rigidity-Preserving Team Partitions in Multiagent Networks.
AB  - Motivated by the strong influence network rigidity has on collaborative systems,
      in this paper, we consider the problem of partitioning a multiagent network into
      two sub-teams, a bipartition, such that the resulting sub-teams are topologically
      rigid. In this direction, we determine the existence conditions for rigidity
      preserving bipartitions, and provide an iterative algorithm that identifies such
      partitions in polynomial time. In particular, the relationship between rigid
      graph partitions and the previously identified Z-link edge structure is given,
      yielding a feasible direction for graph search. Adapting a supergraph search
      mechanism, we then detail a methodology for discerning graphs cuts that represent
      valid rigid bipartitions. Next, we extend our methods to a decentralized context
      by exploiting leader election and an improved graph search to evaluate feasible
      cuts using only local agent-to-agent communication. Finally, full algorithm
      details and pseudocode are provided, together with simulation results that verify
      correctness and demonstrate complexity. 

PMID- 25561601
TI  - Receding Horizon Stabilization and Disturbance Attenuation for Neural Networks
      With Time-Varying Delay.
AB  - This paper is concerned with the problems of receding horizon stabilization and
      disturbance attenuation for neural networks with time-varying delay. New delay
      dependent conditions on the terminal weighting matrices of a new finite horizon
      cost functional for receding horizon stabilization are established for neural
      networks with time-varying or time-invariant delays using single- and double
      integral Wirtinger-type inequalities. Based on the results, delay-dependent
      sufficient conditions for the receding horizon disturbance attenuation are given
      to guarantee the infinite horizon Hinfinity performance of neural networks with
      time-varying or time-invariant delays. Three numerical examples are provided to
      illustrate the effectiveness of the proposed approach. 

PMID- 25561602
TI  - Mining Spatial-Temporal Patterns and Structural Sparsity for Human Motion Data
      Denoising.
AB  - Motion capture is an important technique with a wide range of applications in
      areas such as computer vision, computer animation, film production, and medical
      rehabilitation. Even with the professional motion capture systems, the acquired
      raw data mostly contain inevitable noises and outliers. To denoise the data,
      numerous methods have been developed, while this problem still remains a
      challenge due to the high complexity of human motion and the diversity of real
      life situations. In this paper, we propose a data-driven-based robust human
      motion denoising approach by mining the spatial-temporal patterns and the
      structural sparsity embedded in motion data. We first replace the regularly used
      entire pose model with a much fine-grained partlet model as feature
      representation to exploit the abundant local body part posture and movement
      similarities. Then, a robust dictionary learning algorithm is proposed to learn
      multiple compact and representative motion dictionaries from the training data in
      parallel. Finally, we reformulate the human motion denoising problem as a robust
      structured sparse coding problem in which both the noise distribution information
      and the temporal smoothness property of human motion have been jointly taken into
      account. Compared with several state-of-the-art motion denoising methods on both
      the synthetic and real noisy motion data, our method consistently yields better
      performance than its counterparts. The outputs of our approach are much more
      stable than that of the others. In addition, it is much easier to setup the
      training dataset of our method than that of the other data-driven-based methods. 

PMID- 25561603
TI  - Efficient Video Stitching Based on Fast Structure Deformation.
AB  - In computer vision, video stitching is a very challenging problem. In this paper,
      we proposed an efficient and effective wide-view video stitching method based on
      fast structure deformation that is capable of simultaneously achieving quality
      stitching and computational efficiency. For a group of synchronized frames,
      firstly, an effective double-seam selection scheme is designed to search two
      distinct but structurally corresponding seams in the two original images. The
      seam location of the previous frame is further considered to preserve the
      interframe consistency. Secondly, along the double seams, 1-D feature detection
      and matching is performed to capture the structural relationship between the two
      adjacent views. Thirdly, after feature matching, we propose an efficient
      algorithm to linearly propagate the deformation vectors to eliminate structure
      misalignment. At last, image intensity misalignment is corrected by rapid
      gradient fusion based on the successive over relaxation iteration (SORI) solver.
      A principled solution to the initialization of the SORI significantly reduced the
      number of iterations required. We have compared favorably our method with seven
      state-of-the-art image and video stitching algorithms as well as traditional
      ones. Experimental results show that our method outperforms the existing ones
      compared in terms of overall stitching quality and computational efficiency. 

PMID- 25561604
TI  - Adaptive Fuzzy Tracking Control for a Class of MIMO Nonlinear Systems in
      Nonstrict-Feedback Form.
AB  - This paper focuses on the problem of fuzzy adaptive control for a class of
      multiinput and multioutput (MIMO) nonlinear systems in nonstrict-feedback form,
      which contains the strict-feedback form as a special case. By the condition of
      variable partition, a new fuzzy adaptive backstepping is proposed for such a
      class of nonlinear MIMO systems. The suggested fuzzy adaptive controller
      guarantees that the proposed control scheme can guarantee that all the signals in
      the closed-loop system are semi-globally uniformly ultimately bounded and the
      tracking errors eventually converge to a small neighborhood around the origin.
      The main advantage of this paper is that a control approach is systematically
      derived for nonlinear systems with strong interconnected terms which are the
      functions of all states of the whole system. Simulation results further
      illustrate the effectiveness of the suggested approach. 

PMID- 25561605
TI  - Large Tanker Motion Model Identification Using Generalized Ellipsoidal Basis
      Function-Based Fuzzy Neural Networks.
AB  - In this paper, the motion dynamics of a large tanker is modeled by the
      generalized ellipsoidal function-based fuzzy neural network (GEBF-FNN). The
      reference model of tanker motion dynamics in the form of nonlinear difference
      equations is established to generate training data samples for the GEBF-FNN
      algorithm which begins with no hidden neuron. In the sequel, fuzzy rules
      associated with the GEBF-FNN-based model can be online self-constructed by
      generation criteria and parameter estimation, and can dynamically capture
      essential motion dynamics of the large tanker with high prediction accuracy.
      Simulation studies and comprehensive comparisons are conducted on typical zig-zag
      maneuvers with moderate and extreme steering, and demonstrate that the GEBF-FNN
      based model of tanker motion dynamics achieves superior performance in terms of
      both approximation and prediction. 

PMID- 25561607
TI  - ToxCastTM wants you: recommendations for engaging the broader scientific
      community.

PMID- 25561606
TI  - In search of "just right": the challenge of regulating arsenic in rice.

PMID- 25561608
TI  - Inner workings of arsenic: DNA methylation targets offer clues to mechanisms of
      toxicity.

PMID- 25561609
TI  - "Exported" deaths and short-term PM10 exposure: factoring the impact of commuting
      into mortality estimates.

PMID- 25561610
TI  - Potential mitochondrial toxicants: Tox21 screen identifies structures of
      interest.

PMID- 25561611
TI  - The WASH approach: fighting waterborne diseases in emergency situations.

PMID- 25561612
TI  - Changes in Quitline Caller Characteristics During a National Tobacco Education
      Campaign.
AB  - INTRODUCTION: The Centers for Disease Control and Prevention launched the first
      federally-funded national tobacco education campaign, "Tips From Former Smokers"
      (Tips), in 2012. This study examined changes in quitline caller characteristics,
      including demographics and smoking-related behaviors before and during the Tips
      campaign. METHODS: Using quitline data from 20 U.S. states and the District of
      Columbia, we examined characteristics of 76,933 callers during the Tips campaign
      (March 19, 2012 to June 10, 2012) compared to 44,710 callers from a similar time
      period in 2011 (March 21, 2011 to June 12, 2011). We also examined whether
      characteristics differed by self-reported awareness of Tips during the campaign
      in 13 quitlines that added a Tips awareness question. Group differences were
      assessed using chi-square and t tests, adjusted for clustering by state. RESULTS:
      Overall, few meaningful differences in caller characteristic existed, indicating
      broad reach of the Tips campaign across demographic groups. Compared with 2011,
      the number of callers during Tips increased by 72% and callers were twice as
      likely to hear about the quitline through television media. The proportion of
      uninsured callers was slightly higher during the Tips campaign than in 2011.
      Persons aware of the campaign were slightly more likely to be non-Hispanic
      Blacks, younger than age 55 years, and uninsured than those unaware of the
      campaign. CONCLUSIONS: The Tips campaign increased the reach of quitline services
      to the general population of smokers, with increases across all demographic and
      tobacco use groups, but particularly among those who were uninsured. Such
      campaigns have the potential to increase access to cessation services for the
      uninsured.

PMID- 25561613
TI  - Single-neuron isolation for RNA analysis using pipette capture and laser capture
      microdissection.
AB  - The field of single-cell analysis has greatly benefitted from recent
      technological advances allowing scientists to study genomes, transcriptomes,
      proteomes, and metabolomes at the single-cell level. Transcriptomics allows a
      unique window into cell function and is especially useful for studying global
      variability among single cells of seemingly the same type. Generating
      transcriptome data from RNA samples has become increasingly easy and can be done
      using either microarray or RNA-Seq techniques. RNA isolation is the first step of
      transcriptomics. Numerous RNA isolation procedures exist and differ with respect
      to the type and number of cells from which they are capable of isolating RNA.
      Although it is trivial to isolate RNA from bulk tissue or culture plates,
      sophisticated methods are required to capture RNA from single cells in a pool of
      cells or in intact tissue. We describe here the protocols used for isolating the
      soma of single neurons in cultures and in tissue slices using the pipette capture
      and the PALM or laser capture microdissection (LCM) approaches, respectively. LCM
      was developed to isolate cells from tissue sections primarily for pathological
      tissue analysis. LCM can be used to isolate individual cells or groups of cells
      from ethanol or paraffin-embedded formalin-fixed tissue sections and dissociated
      tissue cultures. The soma isolates from either technique can subsequently be used
      for RNA amplification procedures and transcriptome analysis. These procedures can
      also be adapted to other cell types in cultures and tissue sections and can be
      used on neuronal subcellular structures, such as dendrites. 

PMID- 25561614
TI  - Verifying the function and localization of genetically encoded Ca2+ sensors and
      converting FRET ratios to Ca2+ concentrations.
AB  - Genetically encoded, ratiometric, fluorescent Ca(2+) biosensors can be used in
      living cells to quantitatively measure free Ca(2+) concentrations in the cytosol
      or in organelles. This protocol describes how to perform a calibration of a
      Ca(2+) sensor expressed in cultured mammalian cells as images are acquired using
      a widefield fluorescence microscope. This protocol also explains how to calculate
      Forster resonance energy transfer (FRET) ratios from acquired images and how to
      convert FRET ratios to Ca(2+) concentrations. 

PMID- 25561615
TI  - Measuring the in situ Kd of a genetically encoded Ca2+ sensor.
AB  - The use of genetically encoded Ca(2+) sensors (GECIs) for long-term monitoring of
      intracellular Ca(2+) has become increasingly common in the last decade. Emission
      ratiometric GECIs, such as those in the Yellow Cameleon family, can be used to
      make quantitative measurements, meaning that their fluorescence signals can be
      converted to free Ca(2+) concentrations ([Ca(2+)]free). This conversion is only
      as accurate as the sensor's apparent dissociation constant for Ca(2+) (K'd),
      which depends on temperature, pH, and salt concentration. This protocol describes
      a method for performing a titration, in living cells (in situ), of cytosolic,
      nuclear, or mitochondrial sensors. 

PMID- 25561616
TI  - Preclinical magnetic resonance imaging in mouse cancer models.
AB  - The use of magnetic resonance imaging (MRI) in humans and animal models has been
      rapidly growing. MRI provides high spatial resolution, excellent tissue contrast,
      and outstanding definition of the anatomical structure of normal organs and
      tumors. Because MRI does not require genetically encoded reporters, it can be
      used for tumor surveillance and the assessment of treatment effects in a variety
      of mouse cancer models. MRI systems for preclinical imaging typically operate at
      higher magnetic field strength, ranging from 4.7 to 15 T, as opposed to clinical
      MRI scanners, which range from 1.5 to 3 T. The higher field strength of dedicated
      preclinical systems provides higher spatial resolution and higher signal-to-noise
      ratios. MRI of mouse cancer models requires optimization of numerous parameters,
      including pulse sequences and radio frequency coils. Here, we describe a protocol
      covering the general procedures for MRI. 

PMID- 25561617
TI  - Quantitative bioluminescence imaging of mouse tumor models.
AB  - Bioluminescence imaging (BLI) has become an essential technique for preclinical
      evaluation of anticancer therapeutics and provides sensitive and quantitative
      measurements of tumor burden in experimental cancer models. For light generation,
      a vector encoding firefly luciferase is introduced into human cancer cells that
      are grown as tumor xenografts in immunocompromised hosts, and the enzyme
      substrate luciferin is injected into the host. Alternatively, the reporter gene
      can be expressed in genetically engineered mouse models to determine the onset
      and progression of disease. In addition to expression of an ectopic luciferase
      enzyme, bioluminescence requires oxygen and ATP, thus only viable luciferase
      expressing cells or tissues are capable of producing bioluminescence signals.
      Here, we summarize a BLI protocol that takes advantage of advances in hardware,
      especially the cooled charge-coupled device camera, to enable detection of
      bioluminescence in living animals with high sensitivity and a large dynamic
      range. 

PMID- 25561618
TI  - Direct chemical sequencing of end-labeled RNA.
AB  - Chemical sequencing of RNA relies on the fact that each of the four bases in RNA
      is susceptible to chemical modification in a different way. In this protocol, end
      labeled RNAs are subjected to base-specific chemical modification reactions that
      make the RNA strand adjacent to the modified base susceptible to cleavage. The
      chemical modification reaction is base-specific but limited so that not every
      base in every strand is modified. After cleavage, the resulting set of
      radioactive fragments is resolved via polyacrylamide gel electrophoresis. 

PMID- 25561619
TI  - Poisoned primer extension.
AB  - Poisoned primer extension is primarily used to distinguish between RNAs that are
      nearly identical in sequence but cannot be distinguished by standard primer
      extension because they are the same size (e.g., edited vs. nonedited
      transcripts). It is conceptually identical to the standard primer extension
      reaction but involves the use of a chain-terminating dideoxynucleotide (the
      "poison") in the presence of the other three nucleotides. A radioactively labeled
      primer that hybridizes a short-distance downstream from the "changed" region of
      interest is extended by reverse transcription into this region of sequence
      variation. The reactions contain three of the four substrates for extension
      (e.g., dATP, dGTP, and dTTP) and a chain-terminating dideoxynucleotide (e.g.,
      ddCTP). The extension reaction stops when reverse transcriptase adds a chain
      terminating dideoxynucleotide to the template (e.g., it will add ddCTP when it
      encounters a G in the template sequence). RNAs that differ in sequence at that
      position will yield different-sized extension products that can be resolved on a
      denaturing gel. 

PMID- 25561620
TI  - Isolation of microtubules by assembly/disassembly methods.
AB  - The microtubule-isolation procedures described here are based on the ability of
      the investigator to control the dimer-polymer distribution of tubulin by varying
      the temperature of the extract. In general, the extract is warmed to induce
      microtubule assembly, the polymer is collected by centrifugation, cooled to
      induce disassembly, clarified by centrifugation, and then warmed again to produce
      polymer. As long as the GTP supply is sufficient, the microtubules that result
      can be taken through numerous rounds of this in vitro assembly and disassembly
      reaction. Many microtubule-associated proteins (MAPs) associate with microtubules
      assembled in vitro. Some reagents can skew the equilibrium of assembly and
      disassembly toward formation of polymer. The inclusion of glycerol, for instance,
      promotes microtubule assembly by disrupting the hydration shell around the
      tubulin dimers. The result is a greater yield of tubulin per gram of starting
      material. However, the ratio of MAPs to tubulin is slightly lower, presumably
      because the glycerol also decreases the binding of MAPs to tubulin. Two methods
      are described here: The first uses buffer lacking assembly-promoting components,
      and the second uses buffer containing glycerol. These procedures are most
      efficient with vertebrate brain tissue, where the soluble protein can be up to
      15%-20% tubulin. The first produces satisfactory yields when using chick or pig
      brain; the second is recommended for calf or cow brain. The second procedure may
      also be useful for studies of nonneuronal tissues where the relative
      concentration of tubulin per gram of wet weight is considerably lower than that
      of brain. 

PMID- 25561621
TI  - Isolation of microtubules and microtubule-associated proteins using Paclitaxel.
AB  - Paclitaxel binds to tubulin, strongly promotes microtubule assembly from
      subunits, and stabilizes the assembled polymer against disassembly. Because of
      its ability to drive the assembly reaction almost completely toward microtubules,
      the paclitaxel-dependent procedure outlined here is particularly useful for the
      isolation of microtubules from tissues in which the intracellular concentration
      of tubulin is low (e.g., nonneuronal sources, cultured cells, and invertebrate
      tissues). The microtubule-associated proteins (MAPs) remain bound to the
      paclitaxel-stabilized microtubules. The isolation of these MAPs by salt
      extraction is also described here. 

PMID- 25561622
TI  - Separation of tubulin and microtubule-associated proteins by ion exchange
      chromatography.
AB  - Conventional liquid chromatography on phosphocellulose (PC) can be used to
      separate tubulin and microtubule-associated proteins (MAPs). Tubulin is a highly
      acidic protein and thus does not bind to PC. MAPs, however, do bind to PC and can
      be eluted with a subsequent salt wash of the column. 

PMID- 25561623
TI  - Measuring initiator caspase activation by bimolecular fluorescence
      complementation.
AB  - Initiator caspases, including caspase-2, -8, and -9, are activated by the
      proximity-driven dimerization that occurs after their recruitment to activation
      platforms. Here we describe the use of caspase bimolecular fluorescence
      complementation (caspase BiFC) to measure this induced proximity. BiFC assays
      rely on the use of a split fluorescent protein to identify protein-protein
      interactions in cells. When fused to interacting proteins, the fragments of the
      split fluorescent protein (which do not fluoresce on their own) can associate and
      fluoresce. In this protocol, we use the fluorescent protein Venus, a brighter and
      more photostable variant of yellow fluorescent protein (YFP), to detect the
      induced proximity of caspase-2. Plasmids encoding two fusion products (caspase-2
      fused to either the amino- or carboxy-terminal halves of Venus) are transfected
      into cells. The cells are then treated with an activating (death) stimulus. The
      induced proximity (and subsequent activation) of caspase-2 in the cells is
      visualized as Venus fluorescence. The proportion of Venus-positive cells at a
      single time point can be determined using fluorescence microscopy. Alternatively,
      the increase in fluorescence intensity over time can be evaluated by time-lapse
      confocal microscopy. The caspase BiFC strategy described here should also work
      for other initiator caspases, such as caspase-8 or -9, as long as the correct
      controls are used. 

PMID- 25561624
TI  - Measuring caspase activity by Forster resonance energy transfer.
AB  - Forster resonance energy transfer (FRET) occurs across very short distances (in
      the nanometer range) between donor and acceptor fluorophores that overlap in
      their emission and absorption spectra. FRET-compatible green fluorescent protein
      (GFP) variants that are fused to short peptide linkers containing caspase
      cleavage sites can be used to measure caspase activity. In the intact probes, the
      donor and acceptor fluorophores are in close proximity, and FRET is highly
      efficient. On caspase activation, proteolysis of the linker occurs, and the donor
      is separated from the acceptor. This results in a disruption of resonance energy
      transfer and an increase in donor fluorescence quantum yield; this event is
      typically referred to as sensitized emission or donor unquenching. A number of
      highly sensitive FRET probes based on the cyan fluorescent protein-yellow
      fluorescent protein (CFP-YFP) pair, or improved variants thereof, have been
      developed to detect intracellular caspase activities. In this protocol we
      describe how to use FRET-based caspase substrates and time-lapse imaging to
      measure caspase activity in cells undergoing apoptosis. 

PMID- 25561625
TI  - Properties and use of genetically encoded FRET sensors for cytosolic and
      organellar Ca2+ measurements.
AB  - In the last 15 years, there has been an explosion in the development of
      genetically encoded biosensors that report enzyme activity, chemical
      transformation, or concentration of ions and molecules in living cells.
      Currently, there are well over 120 biosensors of different cellular targets. As a
      general design principle, these sensors convert a molecular event, such as the
      binding of a molecule to a sensing domain or a signal-induced change in protein
      conformation, into a change in the sensor's fluorescence properties. In contrast
      to small-molecule sensors, genetically encoded sensors are generated when sensor
      encoding nucleic acid sequences, which have been introduced by transgenic
      technologies, are translated in cells, tissues, or organisms. One of the best
      developed classes of biosensors is the genetically encoded Ca(2+) indicators
      (GECIs). Here, we briefly summarize the properties of ratiometric GECIs and
      describe how they are used to quantify Ca(2+) in specific cellular locations,
      such as the cytosol, nucleus, endoplasmic reticulum, and mitochondria. 

PMID- 25561626
TI  - Imaging-based methods for assessing caspase activity in single cells.
AB  - Caspases, a family of proteases that are essential mediators of apoptosis, are
      divided into two groups: initiator caspases and executioner caspases. Each
      initiator caspase is activated at the apex of its respective pathway, which
      generally leads to the cleavage and activation of executioner caspases.
      Executioner caspases in turn cleave numerous substrates in the cell, leading to
      its demise. Initiator caspases are activated when inactive monomers undergo
      induced proximity to form an active caspase. In contrast, executioner caspases
      are activated by cleavage. Based on this key difference, different imaging
      techniques have been developed to measure caspase activation and activity on a
      single-cell basis. Bimolecular fluorescence complementation (BiFC) is used to
      measure induced proximity of initiator caspases, whereas Forster resonance energy
      transfer (FRET) permits the investigation of caspase-mediated substrate cleavage
      in real time. Because many of the events in apoptosis, including caspase
      activation, are asynchronous in nature, these single-cell imaging techniques have
      proven to be immensely powerful in ordering and dissecting caspase pathways. When
      coupled with parallel detection of additional hallmark events of apoptosis, they
      provide detailed and quantitative kinetic and positional insights into the signal
      transduction pathways that regulate cell death. Here we provide a brief
      introduction into BiFC- and FRET-based imaging of caspase activation and activity
      in single cells. 

PMID- 25561627
TI  - Single- and two-photon fluorescence recovery after photobleaching.
AB  - Fluorescence recovery after photobleaching (FRAP) is a microscopy technique for
      measuring the kinetics of fluorescently labeled molecules and can be applied both
      in vitro and in vivo for two- and three-dimensional systems. This introduction
      discusses the three basic FRAP methods: traditional FRAP, multiphoton FRAP
      (MPFRAP), and FRAP with spatial Fourier analysis (SFA-FRAP). Each discussion is
      accompanied by a description of the mathematical analysis appropriate for
      situations in which the recovery kinetics is dictated by free diffusion. In some
      experiments, the recovery kinetics is dictated by the boundary conditions of the
      system, and FRAP is then used to quantify the connectivity of various
      compartments. Because the appropriate mathematical analysis is independent of the
      bleaching method, the analysis of compartmental connectivity is discussed last,
      in a separate section. 

PMID- 25561629
TI  - Making vulnerability visible: medical repatriation and Canada's migrant
      agricultural workers.

PMID- 25561630
TI  - Chronic symptomatic and microfilaremic loiasis in a returned traveller.

PMID- 25561631
TI  - A woman with a family history of glaucoma.

PMID- 25561632
TI  - Qatar is a research bonanza for foreigners.

PMID- 25561633
TI  - Transport.

PMID- 25561634
TI  - X-ray attenuating lotion: a supplement to shielding.

PMID- 25561635
TI  - Assessment of library instruction to develop student information literacy skills.

PMID- 25561628
TI  - Identification and computational analysis of gene regulatory elements.
AB  - Over the last two decades, advances in experimental and computational
      technologies have greatly facilitated genomic research. Next-generation
      sequencing technologies have made de novo sequencing of large genomes affordable,
      and powerful computational approaches have enabled accurate annotations of
      genomic DNA sequences. Charting functional regions in genomes must account for
      not only the coding sequences, but also noncoding RNAs, repetitive elements,
      chromatin states, epigenetic modifications, and gene regulatory elements. A mix
      of comparative genomics, high-throughput biological experiments, and machine
      learning approaches has played a major role in this truly global effort. Here we
      describe some of these approaches and provide an account of our current
      understanding of the complex landscape of the human genome. We also present
      overviews of different publicly available, large-scale experimental data sets and
      computational tools, which we hope will prove beneficial for researchers working
      with large and complex genomes. 

PMID- 25561636
TI  - Abdominal examination.

PMID- 25561637
TI  - Aging and health.

PMID- 25561638
TI  - Aging in rural America.
AB  - For older Americans, accessing high-quality care can be a challenge. For those in
      rural communities, it's even harder. 

PMID- 25561640
TI  - The invisible homebound: setting quality-of-care standards for home-based primary
      and palliative care.
AB  - Approximately four million adults in the United States are homebound, and many of
      them cannot access office-based primary care. Home-based medical care can improve
      outcomes and reduce health care costs, but this care operates in a quality
      measurement desert, having been largely left out of the national conversation on
      care quality. To address this shortcoming, two of the authors created the
      National Home-Based Primary and Palliative Care Network, an organization whose
      members include exemplary home-based medical practices, professional societies,
      and patient advocacy groups. This article describes the current status of home
      based medical care in the United States and offers a brief narrative of a
      fictional homebound patient and the health events and fragmented care she faces.
      The article then describes the network's quality-of-care framework, which
      includes ten quality-of-care domains, thirty-two standards, and twenty quality
      indicators that are being tested in the field. The same two authors also
      developed a practice-based registry that will be used for quality-of-care
      benchmarking, practice-based quality improvement, performance reporting, and
      comparative effectiveness research. Together, these steps should help bring home
      based medical care further into the mainstream of US health care. 

PMID- 25561639
TI  - Medicare annual preventive care visits: use increased among fee-for-service
      patients, but many do not participate.
AB  - Under the Affordable Care Act (ACA), Medicare coverage expanded in 2011 to fully
      cover annual preventive care visits. We assessed the impact of coverage
      expansion, using 2007-13 data from primary care patients of Medicare-eligible age
      at the Palo Alto Medical Foundation (204,388 patient-years), which serves people
      in four counties near San Francisco, California. We compared trends in preventive
      visits and recommended preventive services among Medicare fee-for-service and
      Medicare health maintenance organization (HMO) patients as well as non-Medicare
      patients ages 65-75 who were covered by private fee-for-service and private HMO
      plans. Among Medicare fee-for-service patients, the annual use of preventive
      visits rose from 1.4 percent before the implementation of the ACA to 27.5 percent
      afterward. This increase was significantly larger than was seen for patients in
      the other insurance groups. Nevertheless, rates of annual preventive care visit
      use among Medicare fee-for-service patients remained 10-20 percentage points
      lower than was the case for people with private coverage (43-44 percent) or those
      in a Medicare HMO (53 percent). ACA policy changes led to increased preventive
      service use by Medicare fee-for-service beneficiaries, which suggests that
      Medicare coverage expansion is an effective way to increase seniors' use of
      preventive services. 

PMID- 25561641
TI  - Nearly half of all Medicare hospice enrollees received care from agencies owned
      by regional or national chains.
AB  - Analyses of ownership in the US hospice sector have focused on the growth of for
      profit hospice care and on aggregate differences in patient populations and
      service use patterns between for-profit and not-for-profit agencies. Such
      comparisons, although useful, do not offer insights about the types of
      organizations within the hospice sector, including the emergence of multiagency
      chains. Using Medicare cost report data for the period 2000-11, we tracked the
      evolution of the US hospice industry. We not only describe the market's
      composition by profit status but also provide new information about the roles of
      regional and national chains. Almost half of all Medicare hospice enrollees in
      2011 received hospice services from a multiagency chain. A handful of companies
      play a prominent role, although the presence of smaller for-profit and not-for
      profit hospice chains also has grown in recent years. By focusing on the role of
      the diverse organizations that provide hospice care, our analyses can help inform
      efforts to monitor and assure quality of care, to assess payment adequacy and
      options for reform, and to facilitate greater transparency and accountability
      within the hospice marketplace. 

PMID- 25561642
TI  - Expectations about future use of long-term services and supports vary by current
      living arrangement.
AB  - Most Americans know little about options for long-term services and supports and
      underestimate their likely future needs for such assistance. Using data from the
      2012 National Health Interview Survey, we examined expectations about future use
      of long-term services and supports among adults ages 40-65 and how these
      expectations varied by current living arrangement. We found differences by living
      arrangement in expectations about both future need for long-term services and
      supports and who would provide such care if needed. Respondents living with minor
      children were the least likely to expect to need long-term services and supports
      and to require paid care if the need arose. In contrast, respondents living alone
      were the most likely to expect that it was "very likely" that they would need
      long-term services and supports and to rely on paid care. Overall, we found a
      disconnect between expectations of use and likely future reality: 60 percent of
      respondents believed that they were unlikely to need long-term services and
      supports in the future, whereas the evidence suggests that nearly 70 percent of
      older adults will need them at some point. These findings both underscore the
      need for programs that encourage people to plan for long-term services and
      supports and indicate that information about living arrangements can be useful in
      developing and targeting such programs. 

PMID- 25561643
TI  - At least half of new Medicare advantage enrollees had switched from traditional
      Medicare during 2006-11.
AB  - With ongoing interest in rising Medicare Advantage enrollment, we examined
      whether the growth in enrollment between 2006 and 2011 was mainly due to new
      beneficiaries choosing Medicare Advantage when they first become eligible for
      Medicare. We also examined the extent to which beneficiaries in traditional
      Medicare switched to Medicare Advantage, and vice versa. We found that 22 percent
      of new Medicare beneficiaries elected Medicare Advantage over traditional
      Medicare in 2011; they accounted for 48 percent of new Medicare Advantage
      enrollees that year. People ages 65-69 switched from traditional Medicare to
      Medicare Advantage at higher-than-average rates. Dual eligibles (people eligible
      for both Medicare and Medicaid) and beneficiaries younger than age sixty-five
      with disabilities disenrolled from Medicare Advantage at higher-than-average
      rates. On average, in each year of the study period we found that fewer than 5
      percent of traditional Medicare beneficiaries switched to Medicare Advantage, and
      a similar percentage of Medicare Advantage enrollees switched to traditional
      Medicare. These results suggest that initial coverage decisions have long-lasting
      effects. 

PMID- 25561644
TI  - Variations in county-level costs between traditional medicare and medicare
      advantage have implications for premium support.
AB  - Concern about the future growth of Medicare spending has led some in Congress and
      elsewhere to promote converting Medicare to a "premium support" system. Under
      premium support, Medicare would provide a "defined contribution" to each Medicare
      beneficiary to purchase either a Medicare Advantage (MA)-type private health plan
      or the traditional Medicare public plan. To better understand the implications of
      such a shift, we compared the average costs per beneficiary of providing Medicare
      benefits at the county level for traditional Medicare and four types of MA plans.
      We found that the relative costs of Medicare Advantage and traditional Medicare
      varied greatly by MA plan type and by geographic location. The costs of health
      maintenance organization-type plans averaged 7 percent less than those of
      traditional Medicare, but the costs of the more loosely structured preferred
      provider organization and private fee-for-service plans averaged 12-18 percent
      more than those of traditional Medicare. In some counties MA plan costs averaged
      28 percent less than costs in traditional Medicare, while in other counties MA
      plan costs averaged 26 percent more than traditional Medicare costs. Enactment of
      a Medicare premium-support proposal could trigger cost increases for
      beneficiaries participating in Medicare Advantage as well as those in traditional
      Medicare. 

PMID- 25561645
TI  - California's Hospital Fair Pricing Act reduced the prices actually paid by
      uninsured patients.
AB  - California's Hospital Fair Pricing Act, passed in 2006, aims to protect uninsured
      patients from paying hospital gross charges: the full, undiscounted prices based
      on each hospital's chargemaster. In this study I examined how the law affects the
      net price actually paid by uninsured patients--a question critical for evaluating
      the law's impact. I found that from 2004 to 2012 the net price actually paid by
      uninsured patients shrank from 6 percent higher than Medicare prices to 68
      percent lower than Medicare prices; the adjusted collection ratio, essentially
      the amount the hospital actually collected for every dollar in gross price
      charged, for uninsured patients dropped from 32 percent to 11 percent; and
      although hospitals have been increasingly less able to generate revenues from
      uninsured patients, they have raised the proportion of services provided to them
      in relation to total services provided to all patients. The substantial
      protection provided to uninsured patients by the California Hospital Fair Pricing
      Act has important implications for federal and state policy makers seeking to
      achieve a similar goal. States or Congress could legislate criteria determining
      the eligibility for discounted charges, mandate a lower price ceiling, and
      regulate for-profit hospitals in regard to uninsured patients.

PMID- 25561646
TI  - Medicare's Hospital Compare quality reports appear to have slowed price increases
      for two major procedures.
AB  - Previous research has found that Hospital Compare, Medicare's public reporting
      initiative, has had little impact on patient outcomes. However, little is known
      about the initiative's impact on hospital prices, which may be significant
      because private insurers are generally well positioned to respond to quality
      information when negotiating prices with hospitals. We estimated difference-in
      differences models of the effects of Hospital Compare quality reporting on
      transaction prices for two major cardiac procedures, coronary artery bypass graft
      (CABG) and percutaneous coronary intervention (PCI). States that had mandated
      their own public reporting systems before the implementation of Hospital Compare
      formed the control group. We found that prices for these procedures continued to
      increase overall after the initiation of Hospital Compare quality scores, but the
      rate of increase was significantly lower in states with no quality reporting
      metrics of their own before Hospital Compare, when compared to the control states
      (annual rates of increase of 4.4 percent versus 8.7 percent for PCI, and 3.9
      percent versus 10.6 percent for CABG, adjusted for overall inflation). This
      finding implies that Hospital Compare provided leverage to purchasers in
      moderating price increases, while adding competitive pressures on hospitals.
      Providing accurate quality information on both hospitals and health plans could
      benefit consumers. 

PMID- 25561647
TI  - Managing chronic illness: physician practices increased the use of care
      management and medical home processes.
AB  - The effective management of patients with chronic illnesses is critical to
      bending the curve of health care spending in the United States and is a crucial
      test for health care reform. In this article we used data from three national
      surveys of physician practices between 2006 and 2013 to determine the extent to
      which practices of all sizes have increased their use of evidence-based care
      management processes associated with patient-centered medical homes for patients
      with asthma, congestive heart failure, depression, and diabetes. We found
      relatively large increases over time in the overall use of these processes for
      small and medium-size practices as well as for large practices. However, the
      large practices used fewer than half of the recommended processes, on average. We
      also identified the individual processes whose use increased the most and show
      that greater use of care management processes is positively associated with
      public reporting of patient experience and clinical quality and with pay-for
      performance. 

PMID- 25561648
TI  - Patient-centered medical homes in Louisiana had minimal impact on Medicaid
      population's use of acute care and costs.
AB  - The patient-centered medical home model of primary care has received considerable
      attention for its potential to improve outcomes and reduce health care costs. Yet
      little information exists about the model's ability to achieve these goals for
      Medicaid patients. We sought to evaluate the effect of patient-centered medical
      home certification of Louisiana primary care clinics on the quality and cost of
      care over time for a Medicaid population. We used a quasi-experimental pre-post
      design with a matched control group to assess the effect of medical home
      certification on outcomes. We found no impact on acute care use and modest
      support for reduced costs and primary care use among medical homes serving higher
      proportions of chronically ill patients. These findings provide preliminary
      results related to the ability of the patient-centered medical home model to
      improve outcomes for Medicaid beneficiaries. The findings support a case-mix
      adjusted payment policy for medical homes going forward. 

PMID- 25561649
TI  - Community health centers employ diverse staffing patterns, which can provide
      productivity lessons for medical practices.
AB  - Community health centers are at the forefront of ambulatory care practices in
      their use of nonphysician clinicians and team-based primary care. We examined
      medical staffing patterns, the contributions of different types of staff to
      productivity, and the factors associated with staffing at community health
      centers across the United States. We identified four different staffing patterns:
      typical, high advanced-practice staff, high nursing staff, and high other medical
      staff. Overall, productivity per staff person was similar across the four
      staffing patterns. We found that physicians make the greatest contributions to
      productivity, but advanced-practice staff, nurses, and other medical staff also
      contribute. Patterns of community health center staffing are driven by numerous
      factors, including the concentration of clinicians in communities, nurse
      practitioner scope-of-practice laws, and patient characteristics such as
      insurance status. Our findings suggest that other group medical practices could
      incorporate more nonphysician staff without sacrificing productivity and thus
      profitability. However, the new staffing patterns that evolve may be affected by
      characteristics of the practice location or the types of patients served. 

PMID- 25561650
TI  - More choice in health insurance marketplaces may reduce the value of the
      subsidies available to low-income enrollees.
AB  - Federal subsidies available to enrollees in health insurance Marketplaces are
      pegged to the premium of the second-lowest-cost silver plan available in each
      rating area (as defined by each state). People who qualify for the subsidy
      contribute a percentage of their income to purchase coverage, and the federal
      government covers the remaining cost up to the price of that premium. Because the
      number of plans offered and plan premiums vary substantially across rating areas,
      the effective value of the subsidy may vary geographically. We found that the
      availability of more plans in a rating area was associated with lower premiums
      but higher deductibles for enrollees in the second-lowest-cost silver plan. In
      rating areas with more than twenty plans, the average deductible in the second
      lowest-cost silver plan was nearly $1,000 higher than it was in rating areas with
      fewer than thirteen plans. Because premium costs for second-lowest-cost silver
      plans are capped, deductibles may be a more salient measure of plan value for
      enrollees than premiums are. Greater standardization of plans or an alternative
      approach to calculating the subsidy could provide a more consistent benefit to
      enrollees across various rating areas. 

PMID- 25561651
TI  - Out-of-pocket health care expenditures, by insurance status, 2007-10.
AB  - Out-of-pocket health care spending in the United States totaled $306.2 billion in
      2010 and represented 11.8 percent of total national health expenditures,
      according to the Centers for Medicare and Medicaid Services' National Health
      Expenditure Accounts. Spending by people with employer-sponsored health insurance
      and those covered by Medicare accounted for over 80 percent of total out-of
      pocket spending. People without comprehensive medical coverage accounted for less
      than 8 percent of all out-of-pocket expenditures in 2010. Between 2007 and 2010
      per person out-of-pocket spending grew most rapidly for people primarily covered
      by employer-sponsored insurance and declined for people primarily covered by
      Medicare and those without coverage. 

PMID- 25561652
TI  - The share of people with high medical costs increased prior to implementation of
      the Affordable Care Act.
AB  - The percentage of Americans with high medical cost burdens--those who spend more
      than 10 percent of their family income on out-of-pocket expenses for health care-
      increased to 19.2 percent in 2011, after having stabilized at 18.2 percent during
      the Great Recession of 2007-09. The increase was driven primarily by growth in
      premium expenses in 2009-11 for people with employer-sponsored coverage. Out-of
      pocket spending on health services, especially for prescription drugs, continued
      to decrease between 2007-09 and 2011. Medical cost burdens were highest for
      income groups most likely to benefit from the Affordable Care Act's coverage
      expansions, including people with private insurance coverage. Those who purchased
      nongroup coverage before the implementation of the health insurance Marketplaces
      in 2014 spent an especially high proportion of their income on health care, and
      over half of these people will qualify for premium subsidies in the Marketplaces.
      Federal subsidies will substantially reduce medical cost burdens for many people
      who do not obtain health insurance through their employers.

PMID- 25561653
TI  - Dependent coverage provision led to uneven insurance gains and unchanged
      mortality rates in young adult trauma patients.
AB  - Insurance coverage has increased among young adults as a result of the Affordable
      Care Act (ACA) provision that allows young adults to remain covered under their
      parents' plans until age twenty-six. However, little is known about the
      provision's effects on the clinical outcomes and insurance coverage of patients
      with trauma--the most frequent cause of death and physical disability among young
      adults. Using 2007-12 data from the National Trauma Data Bank, we conducted a
      difference-in-differences analysis of coverage rates among trauma patients ages
      19-25 (compared to patients ages 26-34, who served as the control group), and we
      examined trauma-relevant outcomes by patient, injury, and hospital
      characteristics. We found a 3.4-percentage-point decrease in uninsurance status
      among younger trauma patients following the policy change. The decrease was
      concentrated among men, non-Hispanic whites, those with relatively less severe
      injuries, and those who presented to nonteaching hospitals. We did not detect
      significant changes in the use of intensive care or in overall mortality. The
      heterogeneous coverage impact of the ACA dependent coverage provision on high-
      versus low-risk trauma patients has implications for future efforts to expand
      coverage.

PMID- 25561654
TI  - Pay-for-performance schemes that use patient and provider categories would reduce
      payment disparities.
AB  - Providers that care for disproportionate numbers of disadvantaged patients tend
      to perform less well than other providers on quality measures commonly used in
      pay-for-performance programs. This can lead to the undesired effect of
      redistributing resources away from providers that most need them to improve care.
      We present a new pay-for-performance scheme that retains the motivational aspects
      of standard incentive designs while avoiding undesired effects. We tested an
      alternative incentive payment approach that started with a standard incentive
      payment allocation but then "post-adjusted" provider payments using predefined
      patient or provider characteristics. We evaluated whether such an approach would
      mitigate the negative effects of redistributions of payments across provider
      organizations in California with disparate patient populations. The post
      adjustment approach nearly doubled payments to disadvantaged provider
      organizations and greatly reduced payment differentials across provider
      organizations according to patients' income, race/ethnicity, and region. The post
      adjustment of payments could be a useful supplement to paying for improvement,
      aligning the goals of disparity reduction and quality improvement. 

PMID- 25561655
TI  - Avoiding unintended incentives in ACO payment models.
AB  - One goal of the Medicare Shared Savings Program for accountable care
      organizations (ACOs) is to reduce Medicare spending for ACOs' patients relative
      to the organizations' spending history. However, we found that current rules for
      setting ACO spending targets (or benchmarks) diminish ACOs' incentives to
      generate savings and may even encourage higher instead of lower Medicare
      spending. Spending in the three years before ACOs enter or renew a contract is
      weighted unequally in the benchmark calculation, with a high weight of 0.6 given
      to the year just before a new contract starts. Thus, ACOs have incentives to
      increase spending in that year to inflate their benchmark for future years and
      thereby make it easier to obtain shared savings from Medicare in the new contract
      period. We suggest strategies to improve incentives for ACOs, including changes
      to the weights used to determine benchmarks and new payment models that base an
      ACO's spending target not only on its own past performance but also on the
      performance of other ACOs or Medicare providers. 

PMID- 25561656
TI  - Watching the clock: a mother's hope for a natural birth in a cesarean culture.
AB  - A physician and mother on giving birth in a culture that increasingly pushes
      women toward cesarean sections. 

PMID- 25561657
TI  - Public health in America: how foundations are contributing.

PMID- 25561659
TI  - Cost-effectiveness and health care costs.

PMID- 25561660
TI  - Cost-effectiveness: the authors reply.

PMID- 25561661
TI  - Personalized medicine: worth its cost?

PMID- 25561662
TI  - Errata.

PMID- 25561663
TI  - Phylogeny, extinction and conservation: embracing uncertainties in a time of
      urgency.
AB  - Evolutionary studies have played a fundamental role in our understanding of life,
      but until recently, they had only a relatively modest involvement in addressing
      conservation issues. The main goal of the present discussion meeting issue is to
      offer a platform to present the available methods allowing the integration of
      phylogenetic and extinction risk data in conservation planning. Here, we identify
      the main knowledge gaps in biodiversity science, which include incomplete
      sampling, reconstruction biases in phylogenetic analyses, partly known species
      distribution ranges, and the difficulty in producing conservation assessments for
      all known species, not to mention that much of the effective biological diversity
      remains to be discovered. Given the impact that human activities have on
      biodiversity and the urgency with which we need to address these issues,
      imperfect assumptions need to be sanctioned and surrogates used in the race to
      salvage as much as possible of our natural and evolutionary heritage. We discuss
      some aspects of the uncertainties found in biodiversity science, such as the
      ideal surrogates for biodiversity, the gaps in our knowledge and the numerous
      available phylogenetic diversity-based methods. We also introduce a series of
      cases studies that demonstrate how evolutionary biology can effectively
      contribute to biodiversity conservation science. 

PMID- 25561664
TI  - A practical guide to the application of the IUCN Red List of Ecosystems criteria.
AB  - The newly developed IUCN Red List of Ecosystems is part of a growing toolbox for
      assessing risks to biodiversity, which addresses ecosystems and their
      functioning. The Red List of Ecosystems standard allows systematic assessment of
      all freshwater, marine, terrestrial and subterranean ecosystem types in terms of
      their global risk of collapse. In addition, the Red List of Ecosystems categories
      and criteria provide a technical base for assessments of ecosystem status at the
      regional, national, or subnational level. While the Red List of Ecosystems
      criteria were designed to be widely applicable by scientists and practitioners,
      guidelines are needed to ensure they are implemented in a standardized manner to
      reduce epistemic uncertainties and allow robust comparisons among ecosystems and
      over time. We review the intended application of the Red List of Ecosystems
      assessment process, summarize 'best-practice' methods for ecosystem assessments
      and outline approaches to ensure operational rigour of assessments. The Red List
      of Ecosystems will inform priority setting for ecosystem types worldwide, and
      strengthen capacity to report on progress towards the Aichi Targets of the
      Convention on Biological Diversity. When integrated with other IUCN knowledge
      products, such as the World Database of Protected Areas/Protected Planet, Key
      Biodiversity Areas and the IUCN Red List of Threatened Species, the Red List of
      Ecosystems will contribute to providing the most complete global measure of the
      status of biodiversity yet achieved. 

PMID- 25561665
TI  - The price of conserving avian phylogenetic diversity: a global prioritization
      approach.
AB  - The combination of rapid biodiversity loss and limited funds available for
      conservation represents a major global concern. While there are many approaches
      for conservation prioritization, few are framed as financial optimization
      problems. We use recently published avian data to conduct a global analysis of
      the financial resources required to conserve different quantities of phylogenetic
      diversity (PD). We introduce a new prioritization metric (ADEPD) that After
      Downlisting a species gives the Expected Phylogenetic Diversity at some future
      time. Unlike other metrics, ADEPD considers the benefits to future PD associated
      with downlisting a species (e.g. moving from Endangered to Vulnerable in the
      International Union for Conservation of Nature Red List). Combining ADEPD scores
      with data on the financial cost of downlisting different species provides a cost
      benefit prioritization approach for conservation. We find that under worst-case
      spending $3915 can save 1 year of PD, while under optimal spending $1 can
      preserve over 16.7 years of PD. We find that current conservation spending
      patterns are only expected to preserve one quarter of the PD that optimal
      spending could achieve with the same total budget. Maximizing PD is only one
      approach within the wider goal of biodiversity conservation, but our analysis
      highlights more generally the danger involved in uninformed spending of limited
      resources. 

PMID- 25561666
TI  - Conserving the functional and phylogenetic trees of life of European tetrapods.
AB  - Protected areas (PAs) are pivotal tools for biodiversity conservation on the
      Earth. Europe has had an extensive protection system since Natura 2000 areas were
      created in parallel with traditional parks and reserves. However, the extent to
      which this system covers not only taxonomic diversity but also other biodiversity
      facets, such as evolutionary history and functional diversity, has never been
      evaluated. Using high-resolution distribution data of all European tetrapods
      together with dated molecular phylogenies and detailed trait information, we
      first tested whether the existing European protection system effectively covers
      all species and in particular, those with the highest evolutionary or functional
      distinctiveness. We then tested the ability of PAs to protect the entire tetrapod
      phylogenetic and functional trees of life by mapping species' target achievements
      along the internal branches of these two trees. We found that the current system
      is adequately representative in terms of the evolutionary history of amphibians
      while it fails for the rest. However, the most functionally distinct species were
      better represented than they would be under random conservation efforts. These
      results imply better protection of the tetrapod functional tree of life, which
      could help to ensure long-term functioning of the ecosystem, potentially at the
      expense of conserving evolutionary history. 

PMID- 25561667
TI  - Losing history: how extinctions prune features from the tree of life.
AB  - Biodiversity provides many valuable services to humanity; however, rapid
      expansion of the human population has placed increasing pressure on natural
      systems, and it has been suggested that we may be entering a sixth mass
      extinction. There is an urgent need, therefore, to prioritize conservation
      efforts if we are to maintain the provisioning of such service in the future.
      Phylogenetic diversity (PD), the summed branch lengths that connect species on
      the tree-of-life, might provide a valuable metric for conservation prioritization
      because it has been argued to capture feature diversity. Frequently, PD is
      estimated in millions of years, and therefore implicitly assumes an evolutionary
      model in which features diverge gradually over time. Here, I explore the expected
      loss of feature diversity when this assumption is violated. If evolution tends to
      slow down over time, as might be the case following adaptive radiations, losses
      of feature diversity might be relatively small. However, if evolution occurs in
      rapid bursts, following a punctuated model, impacts of extinctions might be much
      greater. PD captures many important properties, but if we use it as a proxy for
      feature diversity, we first need to ensure that we have the correct evolutionary
      model. 

PMID- 25561668
TI  - Phylogenetic diversity meets conservation policy: small areas are key to
      preserving eucalypt lineages.
AB  - Evolutionary and genetic knowledge is increasingly being valued in conservation
      theory, but is rarely considered in conservation planning and policy. Here, we
      integrate phylogenetic diversity (PD) with spatial reserve prioritization to
      evaluate how well the existing reserve system in Victoria, Australia captures the
      evolutionary lineages of eucalypts, which dominate forest canopies across the
      state. Forty-three per cent of remaining native woody vegetation in Victoria is
      located in protected areas (mostly national parks) representing 48% of the extant
      PD found in the state. A modest expansion in protected areas of 5% (less than 1%
      of the state area) would increase protected PD by 33% over current levels. In a
      recent policy change, portions of the national parks were opened for development.
      These tourism development zones hold over half the PD found in national parks
      with some species and clades falling entirely outside of protected zones within
      the national parks. This approach of using PD in spatial prioritization could be
      extended to any clade or area that has spatial and phylogenetic data. Our results
      demonstrate the relevance of PD to regional conservation policy by highlighting
      that small but strategically located areas disproportionally impact the
      preservation of evolutionary lineages. 

PMID- 25561669
TI  - Effects of logging and recruitment on community phylogenetic structure in 32
      permanent forest plots of Kampong Thom, Cambodia.
AB  - Ecological communities including tropical rainforest are rapidly changing under
      various disturbances caused by increasing human activities. Recently in Cambodia,
      illegal logging and clear-felling for agriculture have been increasing. Here, we
      study the effects of logging, mortality and recruitment of plot trees on
      phylogenetic community structure in 32 plots in Kampong Thom, Cambodia. Each plot
      was 0.25 ha; 28 plots were established in primary evergreen forests and four were
      established in secondary dry deciduous forests. Measurements were made in 1998,
      2000, 2004 and 2010, and logging, recruitment and mortality of each tree were
      recorded. We estimated phylogeny using rbcL and matK gene sequences and
      quantified phylogenetic alpha and beta diversity. Within communities, logging
      decreased phylogenetic diversity, and increased overall phylogenetic clustering
      and terminal phylogenetic evenness. Between communities, logging increased
      phylogenetic similarity between evergreen and deciduous plots. On the other hand,
      recruitment had opposite effects both within and between communities. The
      observed patterns can be explained by environmental homogenization under logging.
      Logging is biased to particular species and larger diameter at breast height, and
      forest patrol has been effective in decreasing logging. 

PMID- 25561670
TI  - A synthetic phylogeny of freshwater crayfish: insights for conservation.
AB  - Phylogenetic systematics is heading for a renaissance where we shift from
      considering our phylogenetic estimates as a static image in a published paper and
      taxonomies as a hardcopy checklist to treating both the phylogenetic estimate and
      dynamic taxonomies as metadata for further analyses. The Open Tree of Life
      project (opentreeoflife.org) is developing synthesis tools for harnessing the
      power of phylogenetic inference and robust taxonomy to develop a synthetic tree
      of life. We capitalize on this approach to estimate a synthesis tree for the
      freshwater crayfish. The crayfish make an exceptional group to demonstrate the
      utility of the synthesis approach, as there recently have been a number of
      phylogenetic studies on the crayfishes along with a robust underlying taxonomic
      framework. Importantly, the crayfish have also been extensively assessed by an
      IUCN Red List team and therefore have accurate and up-to-date area and
      conservation status data available for analysis within a phylogenetic context.
      Here, we develop a synthesis phylogeny for the world's freshwater crayfish and
      examine the phylogenetic distribution of threat. We also estimate a molecular
      phylogeny based on all available GenBank crayfish sequences and use this tree to
      estimate divergence times and test for divergence rate variation. Finally, we
      conduct EDGE and HEDGE analyses and identify a number of species of freshwater
      crayfish of highest priority in conservation efforts. 

PMID- 25561672
TI  - Phylogenetic diversity, functional trait diversity and extinction: avoiding
      tipping points and worst-case losses.
AB  - The phylogenetic diversity measure, ('PD'), measures the relative feature
      diversity of different subsets of taxa from a phylogeny. At the level of feature
      diversity, PD supports the broad goal of biodiversity conservation to maintain
      living variation and option values. PD calculations at the level of lineages and
      features include those integrating probabilities of extinction, providing
      estimates of expected PD. This approach has known advantages over the
      evolutionarily distinct and globally endangered (EDGE) methods. Expected PD
      methods also have limitations. An alternative notion of expected diversity,
      expected functional trait diversity, relies on an alternative non-phylogenetic
      model and allows inferences of diversity at the level of functional traits.
      Expected PD also faces challenges in helping to address phylogenetic tipping
      points and worst-case PD losses. Expected PD may not choose conservation options
      that best avoid worst-case losses of long branches from the tree of life. We can
      expand the range of useful calculations based on expected PD, including methods
      for identifying phylogenetic key biodiversity areas. 

PMID- 25561671
TI  - The future of evolutionary diversity in reef corals.
AB  - One-third of the world's reef-building corals are facing heightened extinction
      risk from climate change and other anthropogenic impacts. Previous studies have
      shown that such threats are not distributed randomly across the coral tree of
      life, and future extinctions have the potential to disproportionately reduce the
      phylogenetic diversity of this group on a global scale. However, the impact of
      such losses on a regional scale remains poorly known. In this study, we use
      phylogenetic metrics in conjunction with geographical distributions of living
      reef coral species to model how extinctions are likely to affect evolutionary
      diversity across different ecoregions. Based on two measures-phylogenetic
      diversity and phylogenetic species variability-we highlight regions with the
      largest losses of evolutionary diversity and hence of potential conservation
      interest. Notably, the projected loss of evolutionary diversity is relatively low
      in the most species-rich areas such as the Coral Triangle, while many regions
      with fewer species stand to lose much larger shares of their diversity. We also
      suggest that for complex ecosystems like coral reefs it is important to consider
      changes in phylogenetic species variability; areas with disproportionate declines
      in this measure should be of concern even if phylogenetic diversity is not as
      impacted. These findings underscore the importance of integrating evolutionary
      history into conservation planning for safeguarding the future diversity of coral
      reefs. 

PMID- 25561673
TI  - Ensuring the success of IPBES: between interface, market place and parliament.
AB  - After years of protracted negotiations, the Intergovernmental science-policy
      Platform on Biodiversity and Ecosystem Services (IPBES) was finally established
      in 2012. One year on and we have already witnessed two plenary sessions which
      have, so far, defined procedures for nominating members for observatory and
      decision-making panels as well as experts and knowledge holders for the
      compilation of reports. The sessions also determined the work programme for the
      next 4 years (2014-2018). According to its internally formulated criteria, the
      success of IPBES will be determined by how credible, relevant and legitimate its
      institution and operations are. More specifically, these criteria suggest that
      success is contingent on the transparency of the processes within IPBES, the
      autonomy and quality of scientific knowledge, and the early integration of
      different stakeholders and diverse knowledge and value systems. Currently, we see
      IPBES encompassing open and integrative approaches as well as providing a
      convenient trading floor for particulate and opaque agendas formulated elsewhere.
      In any case, without the backing of large and effective publics the policy
      support function of IPBES will be limited. Local capacity building and supporting
      communities to actively participate in research projects dealing with
      biodiversity are essential for furthering a practical and emancipatory
      understanding of the relationship between political and economic decisions, the
      state and functioning of biodiversity and ecosystems, and current and future
      human well-being. 

PMID- 25561674
TI  - Global evolutionary isolation measures can capture key local conservation species
      in Nearctic and Neotropical bird communities.
AB  - Understanding how to prioritize among the most deserving imperilled species has
      been a focus of biodiversity science for the past three decades. Though global
      metrics that integrate evolutionary history and likelihood of loss have been
      successfully implemented, conservation is typically carried out at sub-global
      scales on communities of species rather than among members of complete taxonomic
      assemblages. Whether and how global measures map to a local scale has received
      little scrutiny. At a local scale, conservation-relevant assemblages of species
      are likely to be made up of relatively few species spread across a large
      phylogenetic tree, and as a consequence there are potentially relatively large
      amounts of evolutionary history at stake. We ask to what extent global metrics of
      evolutionary history are useful for conservation priority setting at the
      community level by evaluating the extent to which three global measures of
      evolutionary isolation (evolutionary distinctiveness (ED), average pairwise
      distance (APD) and the pendant edge or unique phylogenetic diversity (PD)
      contribution) capture community-level phylogenetic and trait diversity for a
      large sample of Neotropical and Nearctic bird communities. We find that
      prioritizing the most ED species globally safeguards more than twice the total PD
      of local communities on average, but that this does not translate into increased
      local trait diversity. By contrast, global APD is strongly related to the APD of
      those same species at the community level, and prioritizing these species also
      safeguards local PD and trait diversity. The next step for biologists is to
      understand the variation in the concordance of global and local level scores and
      what this means for conservation priorities: we need more directed research on
      the use of different measures of evolutionary isolation to determine which might
      best capture desirable aspects of biodiversity. 

PMID- 25561675
TI  - Incorporating evolutionary history into conservation planning in biodiversity
      hotspots.
AB  - There is increased evidence that incorporating evolutionary history directly in
      conservation actions is beneficial, particularly given the likelihood that
      extinction is not random and that phylogenetic diversity (PD) is lost at higher
      rates than species diversity. This evidence is even more compelling in
      biodiversity hotspots, such as Madagascar, where less than 10% of the original
      vegetation remains. Here, we use the Leguminosae, an ecologically and
      economically important plant family, and a combination of phylogenetics and
      species distribution modelling, to assess biodiversity patterns and identify
      regions, coevolutionary processes and ecological factors that are important in
      shaping this diversity, especially during the Quaternary. We show evidence that
      species distribution and community PD are predicted by watershed boundaries,
      which enable the identification of a network of refugia and dispersal corridors
      that were perhaps important for maintaining community integrity during past
      climate change. Phylogenetically clustered communities are found in the southwest
      of the island at low elevation and share a suite of morphological characters
      (especially fruit morphology) indicative of coevolution with their main
      dispersers, the extinct and extant lemurs. Phylogenetically over-dispersed
      communities are found along the eastern coast at sea level and may have resulted
      from many independent dispersal events from the drier and more seasonal regions
      of Madagascar. 

PMID- 25561676
TI  - The sampled Red List Index for plants, phase II: ground-truthing specimen-based
      conservation assessments.
AB  - The IUCN Sampled Red List Index (SRLI) is a policy response by biodiversity
      scientists to the need to estimate trends in extinction risk of the world's
      diminishing biological diversity. Assessments of plant species for the SRLI
      project rely predominantly on herbarium specimen data from natural history
      collections, in the overwhelming absence of accurate population data or detailed
      distribution maps for the vast majority of plant species. This creates
      difficulties in re-assessing these species so as to measure genuine changes in
      conservation status, which must be observed under the same Red List criteria in
      order to be distinguished from an increase in the knowledge available for that
      species, and thus re-calculate the SRLI. However, the same specimen data identify
      precise localities where threatened species have previously been collected and
      can be used to model species ranges and to target fieldwork in order to test
      specimen-based range estimates and collect population data for SRLI plant
      species. Here, we outline a strategy for prioritizing fieldwork efforts in order
      to apply a wider range of IUCN Red List criteria to assessments of plant species,
      or any taxa with detailed locality or natural history specimen data, to produce a
      more robust estimation of the SRLI. 

PMID- 25561677
TI  - Towards a general framework for predicting threat status of data-deficient
      species from phylogenetic, spatial and environmental information.
AB  - In taxon-wide assessments of threat status many species remain not included owing
      to lack of data. Here, we present a novel spatial-phylogenetic statistical
      framework that uses a small set of readily available or derivable
      characteristics, including phylogenetically imputed body mass and remotely sensed
      human encroachment, to provide initial baseline predictions of threat status for
      data-deficient species. Applied to assessed mammal species worldwide, the
      approach effectively identifies threatened species and predicts the geographical
      variation in threat. For the 483 data-deficient species, the models predict
      highly elevated threat, with 69% 'at-risk' species in this set, compared with 22%
      among assessed species. This results in 331 additional potentially threatened
      mammals, with elevated conservation importance in rodents, bats and shrews, and
      countries like Colombia, Sulawesi and the Philippines. These findings demonstrate
      the future potential for combining phylogenies and remotely sensed data with
      species distributions to identify species and regions of conservation concern. 

PMID- 25561678
TI  - Why and how might genetic and phylogenetic diversity be reflected in the
      identification of key biodiversity areas?
AB  - 'Key biodiversity areas' are defined as sites contributing significantly to the
      global persistence of biodiversity. The identification of these sites builds from
      existing approaches based on measures of species and ecosystem diversity and
      process. Here, we therefore build from the work of Sgro et al. (2011 Evol. Appl.
      4, 326-337. (doi:10.1111/j.1752-4571.2010.00157.x)) to extend a framework for how
      components of genetic diversity might be considered in the identification of key
      biodiversity areas. We make three recommendations to inform the ongoing process
      of consolidating a key biodiversity areas standard: (i) thresholds for the
      threatened species criterion currently consider a site's share of a threatened
      species' population; expand these to include the proportion of the species'
      genetic diversity unique to a site; (ii) expand criterion for 'threatened
      species' to consider 'threatened taxa' and (iii) expand the centre of endemism
      criterion to identify as key biodiversity areas those sites holding a threshold
      proportion of the compositional or phylogenetic diversity of species (within a
      taxonomic group) whose restricted ranges collectively define a centre of
      endemism. We also recommend consideration of occurrence of EDGE species (i.e.
      threatened phylogenetic diversity) in key biodiversity areas to prioritize
      species-specific conservation actions among sites. 

PMID- 25561680
TI  - Adapting health promotion interventions for ethnic minority groups: a qualitative
      study.
AB  - Adaptation of health interventions has garnered international support across
      academic disciplines and among various health organizations. Through semi
      structured interviews, we sought to explore and understand the perspectives of 26
      health researchers and promoters located in the USA, UK, Australia, New Zealand
      and Norway, working with ethnic minority populations, specifically African-,
      South Asian- and Chinese-origin populations in the areas of smoking cessation,
      increasing physical activity and healthy eating, to better understand how
      adaptation works in practice. We drew on the concepts of intersectionality,
      representation and context from feminist, sociology and human geography
      literature, respectively, to help us understand how adaptations for ethnic groups
      approach the variable of ethnicity. Findings include (i) the intersections of
      ethnicity and demographic variables such as age and gender highlight the
      different ways in which people interact, interpret and participate in adapted
      interventions; (ii) the representational elements of ethnicity such as ancestry
      or religion are more complexly lived than they are defined in adapted
      interventions and (iii) the contextual experiences surrounding ethnicity
      considerations shape the receptivity, durability and continuity of adapted
      interventions. In conclusion, leveraging the experience and expertise of health
      researchers and promoters in light of three social science concepts has deepened
      our understanding of how adaptation works in principle and in practice for ethnic
      minority populations. 

PMID- 25561681
TI  - The DISCUSS Project: Revised Points to Consider for the Derivation of Induced
      Pluripotent Stem Cell Lines From Previously Collected Research Specimens.
AB  - Human somatic cell reprogramming is a leading technology for accelerating disease
      modeling and drug discovery. The Deriving Induced Stem Cells Using Stored
      Specimens (DISCUSS) project is a consensus-building initiative designed to
      consider how human somatic cells obtained under general biomedical research
      protocols can be used in induced pluripotent stem cell (iPSC) derivation. We
      previously published a draft list of points to consider for the use of previously
      collected specimens in iPSC research and then initiated a structured feedback and
      comment process. Here, we present a summary of this feedback and revised list of
      points to consider.

PMID- 25561679
TI  - Multiple drivers of decline in the global status of freshwater crayfish
      (Decapoda: Astacidea).
AB  - Rates of biodiversity loss are higher in freshwater ecosystems than in most
      terrestrial or marine ecosystems, making freshwater conservation a priority.
      However, prioritization methods are impeded by insufficient knowledge on the
      distribution and conservation status of freshwater taxa, particularly
      invertebrates. We evaluated the extinction risk of the world's 590 freshwater
      crayfish species using the IUCN Categories and Criteria and found 32% of all
      species are threatened with extinction. The level of extinction risk differed
      between families, with proportionally more threatened species in the Parastacidae
      and Astacidae than in the Cambaridae. Four described species were Extinct and 21%
      were assessed as Data Deficient. There was geographical variation in the dominant
      threats affecting the main centres of crayfish diversity. The majority of
      threatened US and Mexican species face threats associated with urban development,
      pollution, damming and water management. Conversely, the majority of Australian
      threatened species are affected by climate change, harvesting, agriculture and
      invasive species. Only a small proportion of crayfish are found within the
      boundaries of protected areas, suggesting that alternative means of long-term
      protection will be required. Our study highlights many of the significant
      challenges yet to come for freshwater biodiversity unless conservation planning
      shifts from a reactive to proactive approach. 

PMID- 25561682
TI  - Therapeutic Potential of Adipose-Derived SSEA-3-Positive Muse Cells for Treating
      Diabetic Skin Ulcers.
AB  - Stage-specific embryonic antigen-3 (SSEA-3)-positive multipotent mesenchymal
      cells (multilineage differentiating stress-enduring [Muse] cells) were isolated
      from cultured human adipose tissue-derived stem/stromal cells (hASCs) and
      characterized, and their therapeutic potential for treating diabetic skin ulcers
      was evaluated. Cultured hASCs were separated using magnetic-activated cell
      sorting into positive and negative fractions, a SSEA-3+ cell-enriched fraction
      (Muse-rich) and the remaining fraction (Muse-poor). Muse-rich hASCs showed
      upregulated and downregulated pluripotency and cell proliferation genes,
      respectively, compared with Muse-poor hASCs. These cells also released higher
      amounts of certain growth factors, particularly under hypoxic conditions,
      compared with Muse-poor cells. Skin ulcers were generated in severe combined
      immunodeficiency (SCID) mice with type 1 diabetes, which showed delayed wound
      healing compared with nondiabetic SCID mice. Treatment with Muse-rich cells
      significantly accelerated wound healing compared with treatment with Muse-poor
      cells. Transplanted cells were integrated into the regenerated dermis as vascular
      endothelial cells and other cells. However, they were not detected in the
      surrounding intact regions. Thus, the selected population of ASCs has greater
      therapeutic effects to accelerate impaired wound healing associated with type 1
      diabetes. These cells can be achieved in large amounts with minimal morbidity and
      could be a practical tool for a variety of stem cell-depleted or ischemic
      conditions of various organs and tissues.

PMID- 25561684
TI  - B-type natriuretic peptide: another brick in the wall towards better risk
      stratification in repaired tetralogy of Fallot.

PMID- 25561683
TI  - Safety and feasibility for pediatric cardiac regeneration using epicardial
      delivery of autologous umbilical cord blood-derived mononuclear cells established
      in a porcine model system.
AB  - Congenital heart diseases (CHDs) requiring surgical palliation mandate new
      treatment strategies to optimize long-term outcomes. Despite the mounting
      evidence of cardiac regeneration, there are no long-term safety studies of
      autologous cell-based transplantation in the pediatric setting. We aimed to
      establish a porcine pipeline to evaluate the feasibility and long-term safety of
      autologous umbilical cord blood mononuclear cells (UCB-MNCs) transplanted into
      the right ventricle (RV) of juvenile porcine hearts. Piglets were born by
      caesarean section to enable UCB collection. Upon meeting release criteria, 12
      animals were randomized in a double-blinded fashion prior to surgical delivery of
      test article (n=6) or placebo (n=6). The UCB-MNC (3*10(6) cells per kilogram) or
      control (dimethyl sulfoxide, 10%) products were injected intramyocardially into
      the RV under direct visualization. The cohorts were monitored for 3 months after
      product delivery with assessments of cardiac performance, rhythm, and serial
      cardiac biochemical markers, followed by terminal necropsy. No mortalities were
      associated with intramyocardial delivery of UCB-MNCs or placebo. Two animals from
      the placebo group developed local skin infection after surgery that responded to
      antibiotic treatment. Electrophysiological assessments revealed no arrhythmias in
      either group throughout the 3-month study. Two animals in the cell-therapy group
      had transient, subclinical dysrhythmia in the perioperative period, likely
      because of an exaggerated response to anesthesia. Overall, this study
      demonstrated that autologous UCB-MNCs can be safely collected and surgically
      delivered in a pediatric setting. The safety profile establishes the foundation
      for cell-based therapy directed at the RV of juvenile hearts and aims to
      accelerate cell-based therapies toward clinical trials for CHD.

PMID- 25561685
TI  - Allopurinol use and risk of non-fatal acute myocardial infarction.
AB  - OBJECTIVES: To quantify the risk of non-fatal acute myocardial infarction (AMI)
      among users of allopurinol. METHODS: We carried out a population-based case
      control study over the period 2001-2007 in patients aged 40-90 years. Patients
      who had prescriptions of allopurinol or an episode of AMI before the start date
      of follow-up were excluded from the main analysis. Allopurinol initiators were
      classified as current users if their last prescription ended in the 30-day window
      before the recorded date of AMI for cases and a random date for controls. The
      association between use of allopurinol and non-fatal AMI was measured through an
      OR and adjusted for confounding factors by an unconditional logistic regression.
      RESULTS: We identified 3171 cases of non-fatal AMI and 18 525 controls. Cases had
      a lower prevalence of current use of allopurinol (0.82%) than controls (1.03%),
      yielding to an OR of 0.52 (95% CI 0.33 to 0.83). The decreased risk was driven by
      men (OR in men=0.44; 95% CI 0.25 to 0.76; OR in women=0.90; 0.36 to 2.23). No
      difference by age was observed. The effect was only observed at higher doses (300
      mg or greater OR=0.30; 0.13 to 0.72; <300 mg OR=0.67; 0.37 to 1.23) and with
      prolonged treatments (<31 days, OR=1.12 (0.55 to 2.29); 31-180 days, OR=0.61;
      0.29 to 1.29; >180 days OR=0.21; 0.08 to 0.53; p for trend=0.001). Among those
      with a previous AMI, allopurinol use also showed a significant reduced risk of
      recurrence (OR=0.16; 0.04 to 0.76). CONCLUSIONS: The present study supports the
      hypothesis that allopurinol is associated with a reduced risk of non-fatal AMI,
      which seems to be dose-dependent and duration-dependent.

PMID- 25561686
TI  - Association between anti-human heat shock protein-60 and interleukin-2 with
      coronary artery calcium score.
AB  - INTRODUCTION: Based upon evidence suggesting that concentrations of anti-heat
      shock protein-60 (anti-HSP60) and interleukin-2 (IL-2) are associated with
      atherogenesis, we tested the hypothesis that anti-HSP60 and IL-2 are associated
      with coronary artery calcium (CAC) score, a marker of subclinical
      atherosclerosis. METHODS: We evaluated 998 asymptomatic adults, age 45-84 years,
      without known coronary disease from the Multi-Ethnic Study of Atherosclerosis
      (MESA), who had anti-HSP60 measured at baseline. Tertiles of serum anti-HSP60
      were evaluated. The associations of IL-2 and anti-HSP60 with CAC were assessed
      using multivariate analyses, with adjustments for coronary risk factors and
      Framingham risk score. RESULTS: Patients' demographics, diabetes, hypertension,
      obesity, or dyslipidaemia did not show differences in levels of anti-HSP60. The
      median (IQR) Framingham risk score was 11 (5-22), 8 (5-16), and 9 (5-18) for the
      first, second, and third tertiles, respectively (p=0.043). IL-2 and tumour
      necrosis factor alpha (TNF-alpha) were associated with increased CAC (IL-2: OR
      3.70, p<0.001; TNF-alpha: OR 4.63, p<0.001). In multivariate regression, the
      highest tertiles of anti-HSP60 and IL-2 were associated with increased risk of
      CAC (HSP60 T3: OR 1.49, p=0.022; IL-2: OR 2.49, p<0.001). After adjustment,
      significant progression of CAC was observed in patients with higher baseline
      levels of anti-HSP60 (estimate 31.73, p=0.016) and IL-2 (estimate 34.39,
      p=0.024). CONCLUSIONS: Increased concentrations of inflammatory markers (IL-2 and
      anti-HSP60) are associated with an increased CAC at baseline and follow-up in
      healthy asymptomatic adults. Future studies should be carried out to assess its
      association with early development of atherosclerosis.

PMID- 25561687
TI  - Temporal trends in the use of reperfusion therapy and outcomes in elderly
      patients with first ST elevation myocardial infarction.
AB  - AIMS: To analyze secular trends in management and short and long-term prognosis
      of elderly presenting with ST-elevation myocardial infarction (STEMI). METHODS
      AND RESULTS: All patients >= 75 years with first STEMI admitted to our Coronary
      Care Unit between 1988 and 2008 were included. Baseline characteristics, clinical
      management, in-hospital and post-discharge outcomes in 4 time periods (1988-1993,
      1994-1998, 1999-2003, 2004-2008) were compared. The final cohort consisted of
      1393 patients. During the study period, there was a significant increase in the
      use of aspirin, beta-blockers and ACE inhibitors. A significant reduction in the
      development of cardiogenic shock and mechanical complications was noticed. The
      use of reperfusion therapy increased significantly, due to a wider use of primary
      percutaneous coronary intervention (PPCI) while 30-days, 1-year and 5-year
      mortality decreased throughout the 20-year study period (p<0.001). In the
      multivariable logistic regression model, patients treated with PPCI showed a
      significantly lower 30-day (OR 0.47, 95% CI, 0.31-0.71), 1-year (OR 0.62, 95% CI
      0.43-0.88) and 5-year mortality (OR 0.57, 95% CI 0.41-0.79) while patients
      receiving fibrinolysis showed a non-significant improvement in 30-day (OR 0.86,
      95% CI 0.62-1.49), 1-year (OR 0.86, 95% CI 0.58-1.30) and 5-year mortality (OR
      0.82, 95% CI 0.56-1.19). CONCLUSION: The use of reperfusion therapy, and
      particularly of PPCI, for elderly patients suffering from STEMI increased
      significantly during the study period. This change in therapy was associated with
      a marked improvement in short and long-term prognosis.

PMID- 25561689
TI  - Hepatic lentiviral gene transfer prevents the long-term onset of hepatic tumours
      of glycogen storage disease type 1a in mice.
AB  - Glycogen storage disease type 1a (GSD1a) is a rare disease due to the deficiency
      in the glucose-6-phosphatase (G6Pase) catalytic subunit (encoded by G6pc), which
      is essential for endogenous glucose production. Despite strict diet control to
      maintain blood glucose, patients with GSD1a develop hepatomegaly, steatosis and
      then hepatocellular adenomas (HCA), which can undergo malignant transformation.
      Recently, gene therapy has attracted attention as a potential treatment for
      GSD1a. In order to maintain long-term transgene expression, we developed an HIV
      based vector, which allowed us to specifically express the human G6PC cDNA in the
      liver. We analysed the efficiency of this lentiviral vector in the prevention of
      the development of the hepatic disease in an original GSD1a mouse model, which
      exhibits G6Pase deficiency exclusively in the liver (L-G6pc(-/-) mice).
      Recombinant lentivirus were injected in B6.G6pc(ex3lox/ex3lox). SA(creERT2/w)
      neonates and G6pc deletion was induced by tamoxifen treatment at weaning.
      Magnetic resonance imaging was then performed to follow up the development of
      hepatic tumours. Lentiviral gene therapy restored glucose-6 phosphatase activity
      sufficient to correct fasting hypoglycaemia during 9 months. Moreover, lentivirus
      treated L-G6pc(-/-) mice presented normal hepatic triglyceride levels, whereas
      untreated mice developed steatosis. Glycogen stores were also decreased although
      liver weight remained high. Interestingly, lentivirus-treated L-G6pc(-/-) mice
      were protected against the development of hepatic tumours after 9 months of gene
      therapy while most of untreated L-G6pc(-/-) mice developed millimetric HCA. Thus
      the treatment of newborns by recombinant lentivirus appears as an attractive
      approach to protect the liver from the development of steatosis and hepatic
      tumours associated to GSD1a pathology. 

PMID- 25561691
TI  - Clinical Laboratories Accreditation Program of the Brazilian Society of Clinical
      Pathology/Laboratory Medicine (PALC/SBPC-ML): 15-Year Experience.

PMID- 25561690
TI  - CRIM1 haploinsufficiency causes defects in eye development in human and mouse.
AB  - Colobomatous macrophthalmia with microcornea syndrome (MACOM, Online Mendelian
      Inheritance in Man (OMIM) 602499) is an autosomal dominantly inherited
      malformation of the eye, which is characterized by microcornea with increased
      axial length, coloboma of the iris and of the optic disc, and severe myopia. We
      performed whole-exome sequencing (WES) in two affected individuals from the 2p23
      p16-linked MACOM family, which includes 13 affected individuals in 3 generations.
      As no shared novel variation was found on the linked haplotype, we performed copy
      number variation (CNV) analysis by comparing the coverage of all exons in the WES
      data sets of the 2 patients with the coverage of 26 control exomes. We identified
      a heterozygous deletion predicted to span 22 kb including exons 14-17 of CRIM1
      (cysteine-rich transmembrane bone morphogenetic protein (BMP) regulator 1).
      Quantitative PCR (qPCR) analysis confirmed the deletion, which was present in 11
      affected individuals. Split-read analysis of WES data followed by breakpoint PCR
      and Sanger sequencing determined both breakpoints flanked by a 4-bp microhomology
      (CTTG). In the mouse, Crim1 is a growth-factor-binding protein with pleiotropic
      roles in the development of multiple organs, including the eye. To investigate
      the role of Crim1 during eye development in mice, we crossed a Crim1(flox) mouse
      line with the Ap2alpha-cre mouse line, which expresses Cre in the head surface
      ectoderm. Strikingly, we observed alterations of eye development in homozygous
      mice leading to severe anatomical and morphological changes overlapping with the
      anomalies observed in MACOM patients. Taken together, these findings identify
      CRIM1 as the causative gene for MACOM syndrome and emphasize the importance of
      CRIM1 in eye development. 

PMID- 25561692
TI  - The SMN structure reveals its crucial role in snRNP assembly.
AB  - The spliceosome plays a fundamental role in RNA metabolism by facilitating pre
      RNA splicing. To understand how this essential complex is formed, we have used
      protein crystallography to determine the first complete structures of the key
      assembler protein, SMN, and the truncated isoform, SMNDelta7, which is found in
      patients with the disease spinal muscular atrophy (SMA). Comparison of the
      structures of SMN and SMNDelta7 shows many similar features, including the
      presence of two Tudor domains, but significant differences are observed in the C
      terminal domain, including 12 additional amino acid residues encoded by exon 7 in
      SMN compared with SMNDelta7. Mapping of missense point mutations found in some
      SMA patients reveals clustering around three spatial locations, with the largest
      cluster found in the C-terminal domain. We propose a structural model of SMN
      binding with the Gemin2 protein and a heptameric Sm ring, revealing a critical
      assembly role of the residues 260-294, with the differences at the C-terminus of
      SMNDelta7 compared with SMN likely leading to loss of small nuclear
      ribonucleoprotein (snRNP) assembly. The SMN complex is proposed to form a dimer
      driven by formation of a glycine zipper involving alpha helix formed by amino
      acid residues 263-294. These results explain how structural changes of SMN give
      rise to loss of SMN-mediated snRNP assembly and support the hypothesis that this
      loss results in atrophy of neurons in SMA. 

PMID- 25561693
TI  - d-Dimer Levels are Significantly Increased in Blood Taken From Varicose Veins
      Compared With Antecubital Blood From the Same Patient.
AB  - d-Dimer is a prothrombotic biomarker and a very sensitive measure of endogenous
      fibrinolysis. It is used as a screening test for suspected deep vein thrombosis.
      This study investigated whether d-dimer levels were increased in the varicose
      veins of patients in comparison to their own arm samples. Patients, n = 24, 17
      male, age 45 (25-91), C2-6, awaiting saphenous laser ablation were compared to
      matched controls, n = 24, 17 male, age 42 (24-89). Concurrent venous blood
      samples were taken from the arm and a lower calf/ankle (varicose) vein. The
      median (interquartile range) d-dimer (ng/mL) level was significantly greater in
      the ankle than in the arm blood of the same patient at 319 (164-631) versus 281
      (167-562), P = .003, Wilcoxon. This did not occur in the controls at 269 (80-564)
      versus 262 (106-526), P = .361, Wilcoxon. The results indicate increased
      endogenous fibrinolysis in varicose veins compared with arm blood. This suggests
      there is more thrombotic activity or dissolution of formed subclinical fibrin
      thrombus which may explain the association of varicose veins with superficial
      vein thrombosis. This contrasts with earlier studies reporting a local reduction
      in fibrinolysis in venous disease.

PMID- 25561694
TI  - Cardiovascular disease risk factors after early-onset preeclampsia, late-onset
      preeclampsia, and pregnancy-induced hypertension.
AB  - Observational studies have shown an increased lifetime risk of cardiovascular
      disease (CVD) in women who experienced a hypertensive disorder in pregnancy. This
      risk is related to the severity of the pregnancy-related hypertensive disease and
      gestational age at onset. However, it has not been investigated whether these
      differences in CVD risk factors are already present at postpartum cardiovascular
      screening. We evaluated postpartum differences in CVD risk factors in 3 subgroups
      of patients with a history of hypertensive pregnancy. We compared the prevalence
      of common CVD risk factors postpartum among 448 women with previous early-onset
      preeclampsia, 76 women with previous late-onset preeclampsia, and 224 women with
      previous pregnancy-induced hypertension. Women with previous early-onset
      preeclampsia were compared with women with late-onset preeclampsia and pregnancy
      induced hypertension and had significantly higher fasting blood glucose (5.29
      versus 4.80 and 4.83 mmol/L), insulin (9.12 versus 6.31 and 6.7 uIU/L),
      triglycerides (1.32 versus 1.02 and 0.97 mmol/L), and total cholesterol (5.14
      versus 4.73 and 4.73 mmol/L). Almost half of the early-onset preeclampsia women
      had developed hypertension, as opposed to 39% and 25% of women in the pregnancy
      induced hypertension and late-onset preeclampsia groups, respectively. Our data
      show differences in the prevalence of common modifiable CVD risk factors
      postpartum and suggest that prevention strategies should be stratified according
      to severity and gestational age of onset for the hypertensive disorders of
      pregnancy. 

PMID- 25561695
TI  - Comparison of psychological functioning in children and their mothers living
      through a life-threatening and non life-threatening chronic disease: A pilot
      study.
AB  - Childhood chronic illness is a potential source of distress and can be a
      traumatic experience both for the child and for the family. Several studies
      highlighted the importance of integrating psychosocial care and standard medical
      practice in the child's care. The current pilot study is the first investigation
      that compared distress in children and their mothers living through a life
      threatening illness (cancer) and a non life-threatening (juvenile rheumatoid
      arthritis) chronic disease. Findings show that there are differences in the
      psychological functioning in children with respect to age. Moreover, the presence
      of posttraumatic stress symptoms in mothers of children with cancer seems to be a
      possible key to understanding the psychological response in this specific
      population.

PMID- 25561696
TI  - The ghost of Nora Batty: A qualitative exploration of the impact of footwear,
      bandaging and hosiery interventions in chronic wound care.
AB  - OBJECTIVE: To explore the impact of footwear, bandaging and hosiery interventions
      in the everyday lives of women and men undergoing treatment for chronic, complex
      wounds in a city in England, UK. METHODS: This study draws on data generated in
      semi-structured interviews with patients exploring outcomes and impacts of
      undergoing treatment for leg and foot ulcers undertaken as part of a UK National
      Institute for Health Research funded study. Footwear, bandaging and hosiery are
      explored here as aspects of material culture, not only in functional terms as a
      treatment supporting or hindering healing but also as part of the means by which
      people receiving treatment for two of the most common complex, chronic wounds,
      leg ulcers and foot ulcers, negotiate and understand their embodied selves in
      everyday life. FINDINGS: Physical and social discomfort associated with
      interventions can lead to ambivalence about effectiveness. Not being able to
      dress appropriately impacts on the ability of people to feel comfortable and take
      part in special occasions and everyday events. In this context, the removal of
      bandaging or refusal to wear support hosiery which may be viewed as 'non
      compliance' by a health professional may feel like a strategy of self-care or
      self-preservation from a patient perspective. DISCUSSION: The study of material
      culture explores how inanimate objects work and how they are worked with in
      carrying out social functions, regulating social relations and giving symbolic
      meaning to human activity. The interviews show some of the ways in which
      footwear, hosiery and bandaging play a role in controlling the boundaries between
      the private (wounded and potentially socially unacceptable smelly, leaky,
      embodied), self and the public presentation of self.

PMID- 25561697
TI  - Foster Caregivers' Perspectives on the Medical Challenges of Children Placed in
      Their Care: Implications for Pediatricians Caring for Children in Foster Care.
AB  - OBJECTIVE: To investigate, using qualitative methodology, foster caregivers'
      perspectives related to the medical needs of children placed in their care. STUDY
      DESIGN: Fifteen foster caregivers were individually interviewed using a
      semistructured open-ended question guide. Data were coded, and the analysis was
      conducted in an inductive manner, allowing themes to emerge from the interviews.
      RESULTS: The following 4 themes were identified: (1) the fragmented histories
      provided to foster caregivers and difficulty in obtaining information; (2) the
      unique medical complications that children in foster care experience; (3) the
      difference between "doing what is expected" and becoming a proactive foster
      caregiver; and (4) the support needs of foster caregivers. CONCLUSIONS: Foster
      caregivers receive insufficient information despite the evidence that these
      children are likely to have complex needs. It is, therefore, necessary for the
      pediatrician to recognize existing medical problems, identify new medical
      problems, educate foster caregivers, and communicate with the multidisciplinary
      team.

PMID- 25561698
TI  - Outcomes of a randomized controlled educational intervention to train pediatric
      residents on caring for children with special health care needs.
AB  - OBJECTIVE: To evaluate an innovative curriculum meeting new pediatric residency
      education guidelines, Special Care Optimization for Patients and Education
      (SCOPE). METHODS: Residents were randomized to intervention (n = 23) or control
      (n = 25) groups. Intervention residents participated in SCOPE, pairing them with
      a child with special health care needs (CSHCN) and faculty mentor to make a home
      visit, complete care coordination toolkits, and participate in case discussions.
      The primary outcome was resident self-efficacy in nine skills in caring for
      CSHCN. Secondary outcomes included curriculum feasibility/acceptance, resident
      attitudes, and family satisfaction. RESULTS: Response rates were >=65%.
      Intervention residents improved in their self-efficacy for setting patient
      centered goals compared with controls (mean change on 4-point Likert-type scale,
      1.36 vs 0.56, P < .05). SCOPE was feasible/acceptable, residents had improved
      attitudes toward CSHCN, and families reported high satisfaction. CONCLUSION:
      SCOPE may serve as a model for efforts to increase residents' self-efficacy in
      their care of patients with chronic disease.

PMID- 25561699
TI  - Continuing education needs of pediatricians across diverse specialties caring for
      children with medical complexity.
AB  - OBJECTIVE: Care for children with medical complexity (CMC) relies on
      pediatricians who often are ill equipped, but striving to provide high quality
      care. We performed a needs assessment of pediatricians across diverse
      subspecialties at a tertiary academic US children's hospital about their
      continuing education needs regarding the care of CMC. METHODS: Eighteen
      pediatricians from diverse subspecialties were asked to complete an online
      anonymous open-ended survey. Data were analyzed using modified grounded theory.
      RESULTS: The response rate was 89% (n = 16). Of participants, 31.2% (n = 5) were
      general pediatricians, 18.7% (n = 3) were hospitalists, and 50% (n = 8) were
      pediatric subspecialists. Pediatricians recognized the need for skills in care
      coordination, giving bad news, working in interprofessional teams, and setting
      goals of care with patients. CONCLUSIONS: Practicing pediatricians need skills to
      improve care for CMC. Strategically incorporating basic palliative care education
      may fill an important training need across diverse pediatric specialties.

PMID- 25561700
TI  - Tibiotalocalcaneal arthrodesis using a straight intramedullary nail.
AB  - BACKGROUND: Tibiotalocalcaneal (TTC) arthrodesis is a proven solution for severe
      hindfoot arthropathy that reestablishes stability for plantigrade gait and
      alleviates pain, while correcting deformity. Intramedullary nailing is an
      effective option for fixation. The aim of this study was to determine clinical
      outcome, analyze the fusion rate, and determine final hindfoot alignment in a
      consecutive series of patients using a single-design straight intramedullary
      nail. METHODS: This study evaluated 63 patients treated between 2006 and 2010
      with at least 36 months of follow-up. Ten patients were excluded because of study
      inclusion criteria, and 4 were lost to follow-up, leaving 49 patients available
      for review. The average follow-up was 70.7 +/- 15.1 months. RESULTS: The American
      Orthopaedic Foot and Ankle Society score improved from 29.7 +/- 15.1 before
      arthrodesis to 65.8 +/- 14.6 after (P < .001) with 83.7% (41/49) of patients
      stating they were satisfied or very satisfied with the outcome. The hindfoot
      angle improved from -3 +/- 15 degrees (varus) before the arthrodesis to 3.5 +/- 4
      degrees (valgus) after; the tibiotalar angle averaged 103 +/- 4.2 degrees after
      the arthrodesis. Fusion occurred in both joints in 86% (42/49) of patients and in
      93% (91/98) of all joints. The average time to fusion was 4.5 +/- 2 months.
      Current smokers had a significantly (P = .03) higher risk of complications. Use
      of an allograft, with or without bone morphogenetic protein 2, led to comparable
      results even in the presence of a large bone defect. CONCLUSION: These results
      are comparable to previously published studies using intramedullary nailing to
      achieve tibiotalocalcaneal arthrodesis. The complication concerns typically
      associated with straight nails were not found. We recommend using a retrograde
      intramedullary nail for the fixation of TTC arthrodesis and adding an allograft
      in cases of significant bone loss. LEVEL OF EVIDENCE: Level IV, consecutive case
      series.

PMID- 25561701
TI  - Ankle arthrodesis after failed total ankle replacement: a systematic review of
      the literature.
AB  - PURPOSE: As the number of total ankle replacements (TARs) performed has risen, so
      has the need for revision. The purpose of this investigation was to perform a
      systematic review of clinical outcomes following a salvage ankle arthrodesis from
      a failed TAR to identify patient- and technique-specific prognostic factors and
      to determine the clinical outcomes and complications following an ankle
      arthrodesis for a failed TAR. METHODS: We searched PubMed, Medline, EMBASE, and
      the Cochrane Central Register of Controlled Trials for studies that analyzed
      ankle fusion after failed TAR with a minimum follow-up of 1 year. RESULTS: We
      included 16 studies (193 patients). The majority of patients (41%) underwent the
      index TAR for rheumatoid arthritis. The majority of these revision surgeries were
      secondary to component loosening, frequently of the talar component (38%). In the
      cases that were revised to an ankle arthrodesis, 81% fused after their first
      arthrodesis procedure. The intercalary bone graft group and the blade plate group
      had the highest rate of fusion after the first attempt at fusion at 100%, whereas
      the tibiotalocalcaneal fusion with cage group had the lowest fusion rate at 50%.
      The overall complication rate was 18.2%, whereas the overall nonunion rate was
      10.6%. CONCLUSION: A salvage ankle arthrodesis for a failed TAR results in
      favorable clinical end points and overall satisfaction at short-term follow-up if
      the patients achieve fusion. The bone graft fusion and blade plate group resulted
      in the highest first-attempt fusion rate, with a low complication rate. Future
      studies should include prospective, comparative control or surgical groups and
      use standardized outcome measurements that will make direct comparisons easier.
      LEVELS: Level IV: Systematic Review of Level IV Studies.

PMID- 25561703
TI  - Measles vaccination.

PMID- 25561704
TI  - Ruptured thoracic aortic aneurysm and aortic dissection are entirely different
      entities.

PMID- 25561688
TI  - Opportunities for improvement in anti-thrombotic therapy and other strategies for
      the management of acute coronary syndromes: Insights from EPICOR, an
      international study of current practice patterns.
AB  - AIMS: To describe international patterns and opportunities for improvement of pre
      and in-hospital care of patients hospitalized for acute coronary syndromes
      (ACS), with special focus on anti-thrombotic therapy. METHODS AND RESULTS: EPICOR
      (long-tErm follow-uP of anti-thrombotic management patterns In acute CORonary
      syndrome patients), an international, cohort study, which enrolled 10,568
      consecutive ACS survivors from 555 hospitals in 20 countries across Europe and
      Latin America (September 2010 to March 2011), prospectively registered detailed
      information on pre- and in-hospital management. Globally, 4738 (44.8%) were
      attended before hospitalization, 4241 (40.1%) had an ECG, 2119 (20%) received
      anti-platelet therapy and 101 STEMI patients (2%) fibrinolysis. In-hospital, 7944
      patients (75.2%) received dual anti-platelet therapy, most often with clopidogrel
      (69.7%), and less with prasugrel (5.4%); 1705 (16.1%) had triple anti-platelet
      therapy, and 849 (8%) single anti-platelet therapy. STEMI patients more often
      received pre-hospital anti-thrombotics, and prasugrel, GP IIb/IIIa inhibitors and
      UFH in-hospital (all p < 0.001). More NSTE-ACS patients received clopidogrel,
      single anti-platelet therapy, and fondaparinux (all p < 0.001). As many as 33% of
      ACS patients were medically managed. A significant decreasing gradient was found
      between Northern, Southern and Eastern Europe and Latin America in use of more
      potent patterns of anti-platelet therapy, reperfusion therapy and invasive
      strategy. CONCLUSION: This large international study shows room for improvement
      in use of anti-thrombotic drugs and other strategies for optimal management of
      ACS, including pre-hospital ECG and anti-thrombotic therapy. Regional practice
      differences not based on evidence or conditioned by economic constraints should
      be reduced.

PMID- 25561705
TI  - Comparative proteomic analysis reveals activation of mucosal innate immune
      signaling pathways during cholera.
AB  - Vibrio cholerae O1 is a major cause of acute watery diarrhea in over 50
      countries. Evidence suggests that V. cholerae O1 may activate inflammatory
      pathways, and a recent study of a Bangladeshi population showed that variants in
      innate immune genes play a role in mediating susceptibility to cholera. We
      analyzed human proteins present in the small intestine of patients infected with
      V. cholerae O1 to characterize the host response to this pathogen. We collected
      duodenal biopsy specimens from patients with acute cholera after stabilization
      and again 30 days after initial presentation. Peptides extracted from biopsy
      specimens were sequenced and quantified using label-free mass spectrometry and
      SEQUEST. Twenty-seven host proteins were differentially abundant between the
      acute and convalescent stages of infection; the majority of these have known
      roles in innate defense, cytokine production, and apoptosis. Immunostaining
      confirmed that two proteins, WARS and S100A8, were more abundant in lamina
      propria cells during the acute stage of cholera. Analysis of the differentially
      abundant proteins revealed the activation of key regulators of inflammation by
      the innate immune system, including Toll-like receptor 4, nuclear factor kappa
      light-chain-enhancer of activated B cells, mitogen-activated protein kinases, and
      caspase-dependent inflammasomes. Interleukin-12beta (IL-12beta) was a regulator
      of several proteins that were activated during cholera, and we confirmed that IL
      12beta was produced by lymphocytes recovered from duodenal biopsy specimens of
      cholera patients. Our study shows that a broad inflammatory response is generated
      in the gut early after onset of cholera, which may be critical in the development
      of long-term mucosal immunity against V. cholerae O1. 

PMID- 25561706
TI  - Phenotypic heterogeneity enables uropathogenic Escherichia coli to evade killing
      by antibiotics and serum complement.
AB  - Uropathogenic strains of Escherichia coli (UPEC) are the major cause of
      bacteremic urinary tract infections. Survival in the bloodstream is associated
      with different mechanisms that help to resist serum complement-mediated killing.
      While the phenotypic heterogeneity of bacteria has been shown to influence
      antibiotic tolerance, the possibility that it makes cells refractory to killing
      by the immune system has not been experimentally tested. In the present study we
      sought to determine whether the heterogeneity of bacterial cultures is relevant
      to bacterial targeting by the serum complement system. We monitored cell
      divisions in the UPEC strain CFT073 with fluorescent reporter protein. Stationary
      phase cells were incubated in active or heat-inactivated human serum in the
      presence or absence of different antibiotics (ampicillin, norfloxacin, and
      amikacin), and cell division and complement protein C3 binding were measured by
      flow cytometry and immunofluorescence microscopy. Heterogeneity in the doubling
      times of CFT073 cells in serum enabled three phenotypically different
      subpopulations to be distinguished, all of them being recognized by the C3
      component of the complement system. The population of rapidly growing cells
      resists serum complement-mediated lysis. The dominant subpopulation of cells with
      intermediate growth rate is susceptible to serum. The third population, which
      does not resume growth upon dilution from stationary phase, is simultaneously
      protected from serum complement and antibiotics. 

PMID- 25561707
TI  - Vibrio cholerae represses polysaccharide synthesis to promote motility in mucosa.
AB  - The viscoelastic mucus layer of gastrointestinal tracts is a host defense barrier
      that a successful enteric pathogen, such as Vibrio cholerae, must circumvent. V.
      cholerae, the causative agent of cholera, is able to penetrate the mucosa and
      colonize the epithelial surface of the small intestine. In this study, we found
      that mucin, the major component of mucus, promoted V. cholerae movement on
      semisolid medium and in liquid medium. A genome-wide screen revealed that Vibrio
      polysaccharide (VPS) production was inversely correlated with mucin-enhanced
      motility. Mucin adhesion assays indicated that VPS bound to mucin. Moreover, we
      found that vps expression was reduced upon exposure to mucin. In an infant mouse
      colonization model, mutants that overexpressed VPS colonized less effectively
      than wild-type strains in more distal intestinal regions. These results suggest
      that V. cholerae is able to sense mucosal signals and modulate vps expression
      accordingly so as to promote fast motion in mucus, thus allowing for rapid spread
      throughout the intestines. 

PMID- 25561708
TI  - Characterization of the effect of the histidine kinase CovS on response regulator
      phosphorylation in group A Streptococcus.
AB  - Two-component gene regulatory systems (TCSs) are a major mechanism by which
      bacteria respond to environmental stimuli and thus are critical to infectivity.
      For example, the control of virulence regulator/sensor kinase (CovRS) TCS is
      central to the virulence of the major human pathogen group A Streptococcus (GAS).
      Here, we used a combination of quantitative in vivo phosphorylation assays,
      isoallelic strains that varied by only a single amino acid in CovS, and
      transcriptome analyses to characterize the impact of CovS on CovR phosphorylation
      and GAS global gene expression. We discovered that CovS primarily serves to
      phosphorylate CovR, thereby resulting in the repression of virulence factor
      encoding genes. However, a GAS strain selectively deficient in CovS phosphatase
      activity had a distinct transcriptome relative to that of its parental strain,
      indicating that both CovS kinase and phosphatase activities influence the CovR
      phosphorylation status. Surprisingly, compared to a serotype M3 strain, serotype
      M1 GAS strains had high levels of phosphorylated CovR, low transcript levels of
      CovR-repressed genes, and strikingly different responses to environmental cues.
      Moreover, the inactivation of CovS in the serotype M1 background resulted in a
      greater decrease in phosphorylated CovR levels and a greater increase in the
      transcript levels of CovR-repressed genes than did CovS inactivation in a
      serotype M3 strain. These data clarify the influence of CovS on the CovR
      phosphorylation status and provide insight into why serotype M1 GAS strains have
      high rates of spontaneous mutations in covS during invasive GAS infection, thus
      providing a link between TCS molecular function and the epidemiology of deadly
      bacterial infections. 

PMID- 25561709
TI  - The sensor histidine kinase RgfC affects group B streptococcal virulence factor
      expression independent of its response regulator RgfA.
AB  - Group B streptococci (GBS; Streptococcus agalactiae) are beta-hemolytic, Gram
      positive bacteria that are common asymptomatic colonizers of healthy adults.
      However, these opportunistic bacteria also cause invasive infections in human
      newborns and in certain adult populations. To adapt to the various environments
      encountered during its disease cycle, GBS encodes a number of two-component
      signaling systems. Previous studies have indicated that the TCS comprising the
      sensor histidine kinase RgfC and the response regulator RgfA mediate GBS binding
      to extracellular matrix components, such as fibrinogen. However, in certain GBS
      clinical isolates, a point mutation in rgfA results in premature truncation of
      the response regulator. The truncated RgfA protein lacks the C-terminal DNA
      binding domain necessary for promoter binding and gene regulation. Here, we show
      that deletion of rgfC in GBS strains lacking a functional RgfA increased systemic
      infection. Furthermore, infection with the rgfC mutant increased induction of
      proinflammatory signaling pathways in vivo. Phosphoproteomic analysis revealed
      that 19 phosphopeptides corresponding to 12 proteins were differentially
      phosphorylated at aspartate, cysteine, serine, threonine, or tyrosine residues in
      the rgfC mutant. This included aspartate phosphorylation of a tyrosine kinase,
      CpsD, and a transcriptional regulator. Consistent with this observation,
      microarray analysis of the rgfC mutant indicated that >200 genes showed altered
      expression compared to the isogenic wild-type strain and included transcriptional
      regulators, transporters, and genes previously associated with GBS pathogenesis.
      Our observations suggest that in the absence of RgfA, nonspecific RgfC signaling
      affects the expression of virulence factors and GBS pathogenesis. 

PMID- 25561710
TI  - Fap2 of Fusobacterium nucleatum is a galactose-inhibitable adhesin involved in
      coaggregation, cell adhesion, and preterm birth.
AB  - Fusobacterium nucleatum is a common oral anaerobe involved in periodontitis that
      is known to translocate and cause intrauterine infections. In the oral
      environment, F. nucleatum adheres to a large diversity of species, facilitating
      their colonization and creating biological bridges that stabilize the
      multispecies dental biofilm. Many of these interactions (called coadherences or
      coaggregations) are galactose sensitive. Galactose-sensitive interactions are
      also involved in the binding of F. nucleatum to host cells. Hemagglutination of
      some F. nucleatum strains is also galactose sensitive, suggesting that a single
      galactose-sensitive adhesin might mediate the interaction of fusobacteria with
      many partners and targets. In order to identify the fusobacterial galactose
      sensitive adhesin, a system for transposon mutagenesis in fusobacteria was
      created. The mutant library was screened for hemagglutination deficiency, and
      three clones were isolated. All three clones were found to harbor the transposon
      in the gene coding for the Fap2 outer membrane autotransporter. The three fap2
      mutants failed to show galactose-inhibitable coaggregation with Porphyromonas
      gingivalis and were defective in cell binding. A fap2 mutant also showed a 2-log
      reduction in murine placental colonization compared to that of the wild type. Our
      results suggest that Fap2 is a galactose-sensitive hemagglutinin and adhesin that
      is likely to play a role in the virulence of fusobacteria. 

PMID- 25561711
TI  - Cyclo(Phe-Pro) produced by the human pathogen Vibrio vulnificus inhibits host
      innate immune responses through the NF-kappaB pathway.
AB  - Cyclo(Phe-Pro) (cFP) is a secondary metabolite produced by certain bacteria and
      fungi. Although recent studies highlight the role of cFP in cell-to-cell
      communication by bacteria, its role in the context of the host immune response is
      poorly understood. In this study, we investigated the role of cFP produced by the
      human pathogen Vibrio vulnificus in the modulation of innate immune responses
      toward the pathogen. cFP suppressed the production of proinflammatory cytokines,
      nitric oxide, and reactive oxygen species in a lipopolysaccharide (LPS)
      stimulated monocyte/macrophage cell line and in bone marrow-derived macrophages.
      Specifically, cFP inhibited inhibitory kappaB (IkappaB) kinase (IKK)
      phosphorylation, IkappaBalpha degradation, and nuclear factor kappaB (NF-kappaB)
      translocation to the cell nucleus, indicating that cFP affects the NF-kappaB
      pathway. We searched for genes that are responsible for cFP production in V.
      vulnificus and identified VVMO6_03017 as a causative gene. A deletion of
      VVMO6_03017 diminished cFP production and decreased virulence in subcutaneously
      inoculated mice. In summary, cFP produced by V. vulnificus actively suppresses
      the innate immune responses of the host, thereby facilitating its survival and
      propagation in the host environment. 

PMID- 25561712
TI  - Natural variant of collagen-like protein a in serotype M3 group a Streptococcus
      increases adherence and decreases invasive potential.
AB  - Group A Streptococcus (GAS) predominantly exists as a colonizer of the human
      oropharynx that occasionally breaches epithelial barriers to cause invasive
      diseases. Despite the frequency of GAS carriage, few investigations into the
      contributory molecular mechanisms exist. To this end, we identified a naturally
      occurring polymorphism in the gene encoding the streptococcal collagen-like
      protein A (SclA) in GAS carrier strains. All previously sequenced invasive
      serotype M3 GAS possess a premature stop codon in the sclA gene truncating the
      protein. The carrier polymorphism is predicted to restore SclA function and was
      infrequently identified by targeted DNA sequencing in invasive strains of the
      same serotype. We demonstrate that a strain with the carrier sclA allele
      expressed a full-length SclA protein, while the strain with the invasive sclA
      allele expressed a truncated variant. An isoallelic mutant invasive strain with
      the carrier sclA allele exhibited decreased virulence in a mouse model of
      invasive disease and decreased multiplication in human blood. Further, the
      isoallelic invasive strain with the carrier sclA allele persisted in the mouse
      nasopharynx and had increased adherence to cultured epithelial cells. Repair of
      the premature stop codon in the invasive sclA allele restored the ability to bind
      the extracellular matrix proteins laminin and cellular fibronectin. These data
      demonstrate that a mutation in GAS carrier strains increases adherence and
      decreases virulence and suggest selection against increased adherence in GAS
      invasive isolates. 

PMID- 25561713
TI  - The secreted effector protein EspZ is essential for virulence of rabbit
      enteropathogenic Escherichia coli.
AB  - Attaching and effacing (A/E) pathogens adhere intimately to intestinal
      enterocytes and efface brush border microvilli. A key virulence strategy of A/E
      pathogens is the type III secretion system (T3SS)-mediated delivery of effector
      proteins into host cells. The secreted protein EspZ is postulated to promote
      enterocyte survival by regulating the T3SS and/or by modulating epithelial
      signaling pathways. To explore the role of EspZ in A/E pathogen virulence, we
      generated an isogenic espZ deletion strain (DeltaespZ) and corresponding cis
      complemented derivatives of rabbit enteropathogenic Escherichia coli and compared
      their abilities to regulate the T3SS and influence host cell survival in vitro.
      For virulence studies, rabbits infected with these strains were monitored for
      bacterial colonization, clinical signs, and intestinal tissue alterations.
      Consistent with data from previous reports, espZ-transfected epithelial cells
      were refractory to infection-dependent effector translocation. Also, the
      DeltaespZ strain induced greater host cell death than did the parent and
      complemented strains. In rabbit infections, fecal DeltaespZ strain levels were 10
      fold lower than those of the parent strain at 1 day postinfection, while the
      complemented strain was recovered at intermediate levels. In contrast to the
      parent and complemented mutants, DeltaespZ mutant fecal carriage progressively
      decreased on subsequent days. DeltaespZ mutant-infected animals gained weight
      steadily over the infection period, failed to show characteristic disease
      symptoms, and displayed minimal infection-induced histological alterations.
      Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling
      (TUNEL) staining of intestinal sections revealed increased epithelial cell
      apoptosis on day 1 after infection with the DeltaespZ strain compared to animals
      infected with the parent or complemented strains. Thus, EspZ-dependent host cell
      cytoprotection likely prevents epithelial cell death and sloughing and thereby
      promotes bacterial colonization. 

PMID- 25561714
TI  - Variation in the susceptibility of Drosophila to different entomopathogenic
      nematodes.
AB  - Entomopathogenic nematodes (EPNs) in the genera Heterorhabditis and Steinernema
      are lethal parasites of insects that are of interest as models for understanding
      parasite-host interactions and as biocontrol agents for insect pests. EPNs harbor
      a bacterial endosymbiont in their gut that assists in insect killing. EPNs are
      capable of infecting and killing a wide range of insects, yet how the nematodes
      and their bacterial endosymbionts interact with the insect immune system is
      poorly understood. Here, we develop a versatile model system for understanding
      the insect immune response to parasitic nematode infection that consists of seven
      species of EPNs as model parasites and five species of Drosophila fruit flies as
      model hosts. We show that the EPN Steinernema carpocapsae, which is widely used
      for insect control, is capable of infecting and killing D. melanogaster larvae.
      S. carpocapsae is associated with the bacterium Xenorhabdus nematophila, and we
      show that X. nematophila induces expression of a subset of antimicrobial peptide
      genes and suppresses the melanization response to the nematode. We further show
      that EPNs vary in their virulence toward D. melanogaster and that Drosophila
      species vary in their susceptibilities to EPN infection. Differences in virulence
      among different EPN-host combinations result from differences in both rates of
      infection and rates of postinfection survival. Our results establish a powerful
      model system for understanding mechanisms of host-parasite interactions and the
      insect immune response to parasitic nematode infection. 

PMID- 25561715
TI  - TfoX-based genetic mapping identifies Vibrio fischeri strain-level differences
      and reveals a common lineage of laboratory strains.
AB  - Bacterial strain variation exists in natural populations of bacteria and can be
      generated experimentally through directed or random mutation. The advent of rapid
      and cost-efficient whole-genome sequencing has facilitated strain-level
      genotyping. Even with modern tools, however, it often remains a challenge to map
      specific traits to individual genetic loci, especially for traits that cannot be
      selected under culture conditions (e.g., colonization level or pathogenicity).
      Using a combination of classical and modern approaches, we analyzed strain-level
      variation in Vibrio fischeri and identified the basis by which some strains lack
      the ability to utilize glycerol as a carbon source. We proceeded to reconstruct
      the lineage of the commonly used V. fischeri laboratory strains. Compared to the
      wild-type ES114 strain, we identify in ES114-L a 9.9-kb deletion with endpoints
      in tadB2 and glpF; restoration of the missing portion of glpF restores the wild
      type phenotype. The widely used strains ESR1, JRM100, and JRM200 contain the same
      deletion, and ES114-L is likely a previously unrecognized intermediate strain in
      the construction of many ES114 derivatives. ES114-L does not exhibit a defect in
      competitive squid colonization but ESR1 does, demonstrating that glycerol
      utilization is not required for early squid colonization. Our genetic mapping
      approach capitalizes on the recently discovered chitin-based transformation
      pathway, which is conserved in the Vibrionaceae; therefore, the specific approach
      used is likely to be useful for mapping genetic traits in other Vibrio species. 

PMID- 25561716
TI  - A metalloprotease secreted by the type II secretion system links Vibrio cholerae
      with collagen.
AB  - Vibrio cholerae is autochthonous to various aquatic niches and is the etiological
      agent of the life-threatening diarrheal disease cholera. The persistence of V.
      cholerae in natural habitats is a crucial factor in the epidemiology of cholera.
      In contrast to the well-studied V. cholerae-chitin connection, scarce information
      is available about the factors employed by the bacteria for the interaction with
      collagens. Collagens might serve as biologically relevant substrates, because
      they are the most abundant protein constituents of metazoan tissues and V.
      cholerae has been identified in association with invertebrate and vertebrate
      marine animals, as well as in a benthic zone of the ocean where organic matter,
      including collagens, accumulates. Here, we describe the characterization of the
      V. cholerae putative collagenase, VchC, encoded by open reading frame VC1650 and
      belonging to the subfamily M9A peptidases. Our studies demonstrate that VchC is
      an extracellular collagenase degrading native type I collagen of fish and
      mammalian origin. Alteration of the predicted catalytic residues coordinating
      zinc ions completely abolished the protein enzymatic activity but did not affect
      the translocation of the protease by the type II secretion pathway into the
      extracellular milieu. We also show that the protease undergoes a maturation
      process with the aid of a secreted factor(s). Finally, we propose that V.
      cholerae is a collagenovorous bacterium, as it is able to utilize collagen as a
      sole nutrient source. This study initiates new lines of investigations aiming to
      uncover the structural and functional components of the V. cholerae collagen
      utilization program. 

PMID- 25561718
TI  - Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers.
AB  - Recent studies have revealed that active enhancers are transcribed, producing a
      class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from
      long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share
      a similar role in the activation of mRNA transcription. Emerging studies, showing
      that eRNAs function in controlling mRNA transcription, challenge the idea that
      enhancers are merely sites of transcription factor assembly. Instead,
      communication between promoters and enhancers can be bidirectional with promoters
      required to activate enhancer transcription. Reciprocally, eRNAs may then
      facilitate enhancer-promoter interaction or activate promoter-driven
      transcription. 

PMID- 25561717
TI  - Biosynthesis of cell envelope-associated phenolic glycolipids in Mycobacterium
      marinum.
AB  - Phenolic glycolipids (PGLs) are polyketide synthase-derived glycolipids unique to
      pathogenic mycobacteria. PGLs are found in several clinically relevant species,
      including various Mycobacterium tuberculosis strains, Mycobacterium leprae, and
      several nontuberculous mycobacterial pathogens, such as M. marinum. Multiple
      lines of investigation implicate PGLs in virulence, thus underscoring the
      relevance of a deep understanding of PGL biosynthesis. We report mutational and
      biochemical studies that interrogate the mechanism by which PGL biosynthetic
      intermediates (p-hydroxyphenylalkanoates) synthesized by the iterative polyketide
      synthase Pks15/1 are transferred to the noniterative polyketide synthase PpsA for
      acyl chain extension in M. marinum. Our findings support a model in which the
      transfer of the intermediates is dependent on a p-hydroxyphenylalkanoyl-AMP
      ligase (FadD29) acting as an intermediary between the iterative and the
      noniterative synthase systems. Our results also establish the p
      hydroxyphenylalkanoate extension ability of PpsA, the first-acting enzyme of a
      multisubunit noniterative polyketide synthase system. Notably, this noniterative
      system is also loaded with fatty acids by a specific fatty acyl-AMP ligase
      (FadD26) for biosynthesis of phthiocerol dimycocerosates (PDIMs), which are
      nonglycosylated lipids structurally related to PGLs. To our knowledge, the
      partially overlapping PGL and PDIM biosynthetic pathways provide the first
      example of two distinct, pathway-dedicated acyl-AMP ligases loading the same type
      I polyketide synthase system with two alternate starter units to produce two
      structurally different families of metabolites. The studies reported here advance
      our understanding of the biosynthesis of an important group of mycobacterial
      glycolipids. 

PMID- 25561719
TI  - Histone variants and epigenetics.
AB  - Histones package and compact DNA by assembling into nucleosome core particles.
      Most histones are synthesized at S phase for rapid deposition behind replication
      forks. In addition, the replacement of histones deposited during S phase by
      variants that can be deposited independently of replication provide the most
      fundamental level of chromatin differentiation. Alternative mechanisms for
      depositing different variants can potentially establish and maintain epigenetic
      states. Variants have also evolved crucial roles in chromosome segregation,
      transcriptional regulation, DNA repair, and other processes. Investigations into
      the evolution, structure, and metabolism of histone variants provide a foundation
      for understanding the participation of chromatin in important cellular processes
      and in epigenetic memory. 

PMID- 25561720
TI  - The blood-brain barrier.
AB  - Blood vessels are critical to deliver oxygen and nutrients to all of the tissues
      and organs throughout the body. The blood vessels that vascularize the central
      nervous system (CNS) possess unique properties, termed the blood-brain barrier,
      which allow these vessels to tightly regulate the movement of ions, molecules,
      and cells between the blood and the brain. This precise control of CNS
      homeostasis allows for proper neuronal function and also protects the neural
      tissue from toxins and pathogens, and alterations of these barrier properties are
      an important component of pathology and progression of different neurological
      diseases. The physiological barrier is coordinated by a series of physical,
      transport, and metabolic properties possessed by the endothelial cells (ECs) that
      form the walls of the blood vessels, and these properties are regulated by
      interactions with different vascular, immune, and neural cells. Understanding how
      these different cell populations interact to regulate the barrier properties is
      essential for understanding how the brain functions during health and disease. 

PMID- 25561722
TI  - Wound healing and skin regeneration.
AB  - The skin is a complex organ consisting of the epidermis, dermis, and skin
      appendages, including the hair follicle and sebaceous gland. Wound healing in
      adult mammals results in scar formation without any skin appendages. Studies have
      reported remarkable examples of scarless healing in fetal skin and appendage
      regeneration in adult skin following the infliction of large wounds. The models
      used in these studies have offered a new platform for investigations of the
      cellular and molecular mechanisms underlying wound healing and skin regeneration
      in mammals. In this article, we will focus on the contribution of skin appendages
      to wound healing and, conversely, skin appendage regeneration following injuries.

PMID- 25561721
TI  - Natural and sun-induced aging of human skin.
AB  - With worldwide expansion of the aging population, research on age-related
      pathologies is receiving growing interest. In this review, we discuss current
      knowledge regarding the decline of skin structure and function induced by the
      passage of time (chronological aging) and chronic exposure to solar UV
      irradiation (photoaging). Nearly every aspect of skin biology is affected by
      aging. The self-renewing capability of the epidermis, which provides vital
      barrier function, is diminished with age. Vital thermoregulation function of
      eccrine sweat glands is also altered with age. The dermal collagenous
      extracellular matrix, which comprises the bulk of skin and confers strength and
      resiliency, undergoes gradual fragmentation, which deleteriously impacts skin
      mechanical properties and dermal cell functions. Aging also affects wound repair,
      pigmentation, innervation, immunity, vasculature, and subcutaneous fat
      homeostasis. Altogether, age-related alterations of skin lead to age-related skin
      fragility and diseases. 

PMID- 25561723
TI  - Mg2+/Mn2+-dependent phosphatase 1A is involved in regulating pregnane X receptor
      mediated cytochrome p450 3A4 gene expression.
AB  - Variations in the expression of human pregnane X receptor (hPXR)-mediated
      cytochrome p450 3A4 (CYP3A4) in liver can alter therapeutic response to a variety
      of drugs and may lead to potential adverse drug interactions. We sought to
      determine whether Mg(2+)/Mn(2+)-dependent phosphatase 1A (PPM1A) regulates hPXR
      mediated CYP3A4 expression. PPM1A was found to be coimmunoprecipitated with hPXR.
      Genetic or pharmacologic activation of PPM1A led to a significant increase in
      hPXR transactivation of CYP3A4 promoter activity. In contrast, knockdown of
      endogenous PPM1A not only attenuated hPXR transactivation, but also increased
      proliferation of HepG2 human liver carcinoma cells, suggesting that PPM1A
      expression levels regulate hPXR, and that PPM1A expression is regulated in a
      proliferation-dependent manner. Indeed, PPM1A expression and hPXR transactivation
      were found to be significantly reduced in subconfluent HepG2 cells compared with
      confluent HepG2 cells, suggesting that both PPM1A expression and hPXR-mediated
      CYP3A4 expression may be downregulated in proliferating livers. Elevated PPM1A
      levels led to attenuation of hPXR inhibition by tumor necrosis factor-alpha and
      cyclin-dependent kinase-2, which are known to be upregulated and essential during
      liver regeneration. In mouse regenerating livers, similar to subconfluent HepG2
      cells, expression of both PPM1A and the mouse PXR target gene cyp3a11 was found
      to be downregulated. Our results show that PPM1A can positively regulate PXR
      activity by counteracting PXR inhibitory signaling pathways that play a major
      role in liver regeneration. These results implicate a novel role for PPM1A in
      regulating hPXR-mediated CYP3A4 expression in hepatocytes and may explain a
      mechanism for CYP3A repression in regenerating livers. 

PMID- 25561724
TI  - Acetylation of TUG protein promotes the accumulation of GLUT4 glucose
      transporters in an insulin-responsive intracellular compartment.
AB  - Insulin causes the exocytic translocation of GLUT4 glucose transporters to
      stimulate glucose uptake in fat and muscle. Previous results support a model in
      which TUG traps GLUT4 in intracellular, insulin-responsive vesicles termed GLUT4
      storage vesicles (GSVs). Insulin triggers TUG cleavage to release the GSVs; GLUT4
      then recycles through endosomes during ongoing insulin exposure. The TUG C
      terminus binds a GSV anchoring site comprising Golgin-160 and possibly other
      proteins. Here, we report that the TUG C terminus is acetylated. The TUG C
      terminal peptide bound the Golgin-160-associated protein, ACBD3 (acyl-CoA-binding
      domain-containing 3), and acetylation reduced binding of TUG to ACBD3 but not to
      Golgin-160. Mutation of the acetylated residues impaired insulin-responsive GLUT4
      trafficking in 3T3-L1 adipocytes. ACBD3 overexpression enhanced the translocation
      of GSV cargos, GLUT4 and insulin-regulated aminopeptidase (IRAP), and ACBD3 was
      required for intracellular retention of these cargos in unstimulated cells.
      Sirtuin 2 (SIRT2), a NAD(+)-dependent deacetylase, bound TUG and deacetylated the
      TUG peptide. SIRT2 overexpression reduced TUG acetylation and redistributed GLUT4
      and IRAP to the plasma membrane in 3T3-L1 adipocytes. Mutation of the acetylated
      residues in TUG abrogated these effects. In mice, SIRT2 deletion increased TUG
      acetylation and proteolytic processing. During glucose tolerance tests, glucose
      disposal was enhanced in SIRT2 knock-out mice, compared with wild type controls,
      without any effect on insulin concentrations. Together, these data support a
      model in which TUG acetylation modulates its interaction with Golgi matrix
      proteins and is regulated by SIRT2. Moreover, acetylation of TUG enhances its
      function to trap GSVs within unstimulated cells and enhances insulin-stimulated
      glucose uptake. 

PMID- 25561725
TI  - Structure of neuroblastoma suppressor of tumorigenicity 1 (NBL1): insights for
      the functional variability across bone morphogenetic protein (BMP) antagonists.
AB  - Bone morphogenetic proteins (BMPs) are antagonized through the action of numerous
      extracellular protein antagonists, including members from the differential
      screening-selected gene aberrative in neuroblastoma (DAN) family. In vivo,
      misregulation of the balance between BMP signaling and DAN inhibition can lead to
      numerous disease states, including cancer, kidney nephropathy, and pulmonary
      arterial hypertension. Despite this importance, very little information is
      available describing how DAN family proteins effectively inhibit BMP ligands.
      Furthermore, our understanding for how differences in individual DAN family
      members arise, including affinity and specificity, remains underdeveloped. Here,
      we present the structure of the founding member of the DAN family, neuroblastoma
      suppressor of tumorigenicity 1 (NBL1). Comparing NBL1 to the structure of protein
      related to Dan and Cerberus (PRDC), a more potent BMP antagonist within the DAN
      family, a number of differences were identified. Through a mutagenesis-based
      approach, we were able to correlate the BMP binding epitope in NBL1 with that in
      PRDC, where introduction of specific PRDC amino acids in NBL1 (A58F and S67Y)
      correlated with a gain-of-function inhibition toward BMP2 and BMP7, but not GDF5.
      Although NBL1(S67Y) was able to antagonize BMP7 as effectively as PRDC,
      NBL1(S67Y) was still 32-fold weaker than PRDC against BMP2. Taken together, this
      data suggests that alterations in the BMP binding epitope can partially account
      for differences in the potency of BMP inhibition within the DAN family. 

PMID- 25561726
TI  - Glycogen synthase kinase-3 (GSK3) inhibition induces prosurvival autophagic
      signals in human pancreatic cancer cells.
AB  - Glycogen synthase kinase-3 (GSK3) are ubiquitously expressed serine-threonine
      kinases involved in a plethora of functions ranging from the control of glycogen
      metabolism to transcriptional regulation. We recently demonstrated that GSK3
      inhibition triggers JNK-cJUN-dependent apoptosis in human pancreatic cancer
      cells. However, the comprehensive picture of downstream GSK3-regulated
      pathways/functions remains elusive. Herein, counterbalancing the death signals,
      we show that GSK3 inhibition induces prosurvival signals through increased
      activity of the autophagy/lysosomal network. Our data also reveal a contribution
      of GSK3 in the regulation of the master transcriptional regulator of autophagy
      and lysosomal biogenesis, transcription factor EB (TFEB) in pancreatic cancer
      cells. Similarly to mammalian target of rapamycin (mTOR) inhibition, GSK3
      inhibitors promote TFEB nuclear localization and leads to TFEB dephosphorylation
      through endogenous serine/threonine phosphatase action. However, GSK3 and mTOR
      inhibition impinge differently and independently on TFEB phosphorylation
      suggesting that TFEB is regulated by a panel of kinases and/or phosphatases.
      Despite their differential impact on TFEB phosphorylation, both GSK3 and mTOR
      inhibitors promote 14-3-3 dissociation and TFEB nuclear localization.
      Quantitative mass spectrometry analyses further reveal an increased association
      of TFEB with nuclear proteins upon GSK3 and mTOR inhibition suggesting a positive
      impact on TFEB transcriptional function. Finally, a predominant nuclear
      localization of TFEB is unveiled in fully fed pancreatic cancer cells, whereas a
      reduction in TFEB expression significantly impairs their capacity for growth in
      an anchorage-independent manner. In addition, TFEB-restricted cells are more
      sensitive to apoptosis upon GSK3 inhibition. Altogether, our data uncover new
      functions under the control of GSK3 in pancreatic cancer cells in addition to
      providing key insight into TFEB regulation. 

PMID- 25561727
TI  - Murine norovirus 1 (MNV1) replication induces translational control of the host
      by regulating eIF4E activity during infection.
AB  - Protein synthesis is a tightly controlled process responding to several stimuli,
      including viral infection. As obligate intracellular parasites, viruses depend on
      the translation machinery of the host and can manipulate it by affecting the
      availability and function of specific eukaryotic initiation factors (eIFs). Human
      norovirus is a member of the Caliciviridae family and is responsible for
      gastroenteritis outbreaks. Previous studies on feline calicivirus and murine
      norovirus 1 (MNV1) demonstrated that the viral protein, genome-linked (VPg), acts
      to direct translation by hijacking the host protein synthesis machinery. Here we
      report that MNV1 infection modulates the MAPK pathway to activate eIF4E
      phosphorylation. Our results show that the activation of p38 and Mnk during MNV1
      infection is important for MNV1 replication. Furthermore, phosphorylated eIF4E
      relocates to the polysomes, and this contributes to changes in the translational
      state of specific host mRNAs. We propose that global translational control of the
      host by eIF4E phosphorylation is a key component of the host-pathogen
      interaction. 

PMID- 25561728
TI  - Mechanism-based proteomic screening identifies targets of thioredoxin-like
      proteins.
AB  - Thioredoxin (Trx)-fold proteins are protagonists of numerous cellular pathways
      that are subject to thiol-based redox control. The best characterized regulator
      of thiols in proteins is Trx1 itself, which together with thioredoxin reductase 1
      (TR1) and peroxiredoxins (Prxs) comprises a key redox regulatory system in
      mammalian cells. However, there are numerous other Trx-like proteins, whose
      functions and redox interactors are unknown. It is also unclear if the principles
      of Trx1-based redox control apply to these proteins. Here, we employed a
      proteomic strategy to four Trx-like proteins containing CXXC motifs, namely Trx1,
      Rdx12, Trx-like protein 1 (Txnl1) and nucleoredoxin 1 (Nrx1), whose cellular
      targets were trapped in vivo using mutant Trx-like proteins, under conditions of
      low endogenous expression of these proteins. Prxs were detected as key redox
      targets of Trx1, but this approach also supported the detection of TR1, which is
      the Trx1 reductant, as well as mitochondrial intermembrane proteins AIF and
      Mia40. In addition, glutathione peroxidase 4 was found to be a Rdx12 redox
      target. In contrast, no redox targets of Txnl1 and Nrx1 could be detected,
      suggesting that their CXXC motifs do not engage in mixed disulfides with cellular
      proteins. For some Trx-like proteins, the method allowed distinguishing redox and
      non-redox interactions. Parallel, comparative analyses of multiple thiol
      oxidoreductases revealed differences in the functions of their CXXC motifs,
      providing important insights into thiol-based redox control of cellular
      processes. 

PMID- 25561729
TI  - A solute carrier family 22 member 3 variant rs3088442 G->A associated with
      coronary heart disease inhibits lipopolysaccharide-induced inflammatory response.
AB  - Recent genome-wide association studies have identified single-nucleotide
      polymorphism (SNPs) within the SLC22A3 (solute carrier family 22 member 3) gene
      associated with coronary heart disease (CHD) in the Caucasian population. We
      performed molecular analysis to investigate the potential role of SLC22A3
      variants in CHD. Our study showed that the common polymorphism rs3088442 G->A,
      which is localized in the 3' UTR of the SLC22A3 gene, was associated with a
      decreased risk of CHD in the Chinese population by a case control study. In
      silico analysis indicated that G->A substitution of SNP rs3088442 created a
      putative binding site for miR-147 in the SLC22A3 mRNA. By overexpressing miR-147
      or inhibiting endogenous miR-147, we demonstrated that SNP rs3088442 G->A
      recruited miR-147 to inhibit SLC22A3 expression. Moreover, SLC22A3 deficiency
      significantly decreased LPS-induced monocytic inflammatory response by
      interrupting NF-kappaB and MAPK signaling cascades in a histamine-dependent
      manner. Notably, the expression of SLC22A3(A) was also suppressed by LPS
      stimulus. Our findings might indicate a negative feedback mechanism against
      inflammatory response by which SLC22A3 polymorphisms decreased the risk of CHD. 

PMID- 25561730
TI  - Ligand binding pocket formed by evolutionarily conserved residues in the glucagon
      like peptide-1 (GLP-1) receptor core domain.
AB  - Glucagon-like peptide-1 (GLP-1) plays a pivotal role in glucose homeostasis
      through its receptor GLP1R. Due to its multiple beneficial effects, GLP-1 has
      gained great attention for treatment of type 2 diabetes and obesity. However,
      little is known about the molecular mechanism underlying the interaction of GLP-1
      with the heptahelical core domain of GLP1R conferring high affinity ligand
      binding and ligand-induced receptor activation. Here, using chimeric and point
      mutated GLP1R, we determined that the evolutionarily conserved amino acid residue
      Arg(380) flanked by hydrophobic Leu(379) and Phe(381) in extracellular loop 3
      (ECL3) may have an interaction with Asp(9) and Gly(4) of the GLP-1 peptide. The
      molecular modeling study showed that Ile(196) at transmembrane helix 2, Met(233)
      at ECL1, and Asn(302) at ECL2 of GLP1R have contacts with His(1) and Thr(7) of
      GLP-1. This study may shed light on the mechanism underlying high affinity
      interaction between the ligand and the binding pocket that is formed by these
      conserved residues in the GLP1R core domain. 

PMID- 25561731
TI  - GRK2 targeted knock-down results in spontaneous hypertension, and altered
      vascular GPCR signaling.
AB  - Hypertension, elevated arterial pressure, occurs as the consequence of increased
      peripheral resistance. G protein-coupled receptors (GPCRs) contribute to the
      regulation of vasodilator and vasoconstrictor responses, and their activity is
      regulated by a family of GPCR kinases (GRKs). GRK2 expression is increased in
      hypertension and this facilitates the development of the hypertensive state by
      increasing the desensitization of GPCRs important for vasodilation. We
      demonstrate here, that genetic knockdown of GRK2 using a small hairpin (sh) RNA
      results in altered vascular reactivity and the development of hypertension
      between 8-12 weeks of age in shGRK2 mice due to enhanced Galphaq/11 signaling.
      Vascular smooth muscle cells (VSMCs) cultured from shGRK2 knockdown mice show
      increases in GPCR-mediated Galphas and Galphaq/11 signaling, as the consequence
      of reduced GRK2-mediated desensitization. In addition, agonists and biased
      agonists exhibited age-dependent alterations in ERK1/2 and Akt signaling, as well
      as cell proliferation and migration responses in shGRK2 knockdown VSMCs when
      cultured from mice that are either 3 months or 6 months of age. Changes in
      angiotensin II-stimulated ERK1/2 phosphorylation are observed in VSMCs derived
      from 6-week-old shGRK2 mice prior to the development of the hypertensive
      phenotype. Thus, our findings indicate that the balance between mechanisms
      regulating vascular tone are shifted to favor vasoconstriction in the absence of
      GRK2 expression and that this leads to the age-dependent development of
      hypertension, as a consequence of global alterations in GPCR signaling.
      Consequently, therapeutic strategies that target GRK2 activity, not expression,
      may be more effective for the treatment of hypertension. 

PMID- 25561732
TI  - Yeast translation elongation factor-1A binds vacuole-localized Rho1p to
      facilitate membrane integrity through F-actin remodeling.
AB  - Rho GTPases are molecular switches that modulate a variety of cellular processes,
      most notably those involving actin dynamics. We have previously shown that yeast
      vacuolar membrane fusion requires re-organization of actin filaments mediated by
      two Rho GTPases, Rho1p and Cdc42p. Cdc42p initiates actin polymerization to
      facilitate membrane tethering; Rho1p has a role in the late stages of vacuolar
      fusion, but its mode of action is unknown. Here, we identified eEF1A as a
      vacuolar Rho1p-interacting protein. eEF1A (encoded by the TEF1 and TEF2 genes in
      yeast) is an aminoacyl-tRNA transferase needed during protein translation. eEF1A
      also has a second function that is independent of translation; it binds and
      organizes actin filaments into ordered cable structures. Here, we report that
      eEF1A interacts with Rho1p via a C-terminal subdomain. This interaction occurs
      predominantly when both proteins are in the GDP-bound state. Therefore, eEF1A is
      an atypical downstream effector of Rho1p. eEF1A does not promote vacuolar fusion;
      however, overexpression of the Rho1p-interacting subdomain affects vacuolar
      morphology. Vacuoles were destabilized and prone to leakage when treated with the
      eEF1A inhibitor narciclasine. We propose a model whereby eEF1A binds to Rho1p-GDP
      on the vacuolar membrane; it is released upon Rho1p activation and then bundles
      actin filaments to stabilize fused vacuoles. Therefore, the Rho1p-eEF1A complex
      acts to spatially localize a pool of eEF1A to vacuoles where it can readily
      organize F-actin. 

PMID- 25561734
TI  - Heavy chain transfer by tumor necrosis factor-stimulated gene 6 to the bikunin
      proteoglycan.
AB  - We present data that hyaluronan (HA) polysaccharides, about 14-86 monosaccharides
      in length, are capable of accepting only a single heavy chain (HC) from inter
      alpha-inhibitor via transfer by tumor necrosis factor-stimulated gene 6 (TSG-6)
      and that this transfer is irreversible. We propose that either the sulfate groups
      (or the sulfation pattern) at the reducing end of the chondroitin sulfate (CS)
      chain of bikunin, or the core protein itself, enables the bikunin proteoglycan
      (PG) to accept more than a single HC and permits TSG-6 to transfer these HCs from
      its relatively small CS chain to HA. To test these hypotheses, we investigated HC
      transfer to the intact CS chain of the bikunin PG, and to the free chain of
      bikunin. We observed that both the free CS chain and the intact bikunin PG were
      only able to accept a single HC from inter-alpha-inhibitor via transfer by TSG-6
      and that HCs could be swapped from the bikunin PG and its free CS chain to HA.
      Furthermore, a significant portion of the bikunin PG was unable to accept a
      single heavy chain. We discuss explanations for these observations, including the
      intracellular assembly of inter-alpha-inhibitor. In summary, these data
      demonstrate that the sulfation of the CS chain of bikunin and/or its core protein
      promote HC transfer by TSG-6 to its relatively short CS chain, although they are
      insufficient to enable the CS chain of bikunin to accept more than one HC in the
      absence of other cofactors. 

PMID- 25561733
TI  - The Na+/H+ exchanger NHE6 modulates endosomal pH to control processing of amyloid
      precursor protein in a cell culture model of Alzheimer disease.
AB  - Early intervention may be key to safe and effective therapies in patients with
      Alzheimer disease. Endosomal dysfunction is an early step in neurodegeneration.
      Endosomes are a major site of production of Abeta peptide from the processing of
      amyloid precursor protein (APP) by clipping enzymes (beta- and gamma-secretases).
      The beta-secretase enzyme BACE1 requires acidic lumen pH for optimum function,
      and acid pH promotes Abeta aggregation. The Na(+)/H(+) exchanger NHE6 provides a
      leak pathway for protons, limiting luminal acidification by proton pumps. Like
      APP, NHE6 expression was induced upon differentiation of SH-SY5Y neuroblastoma
      cells and localized to an endosomal compartment. Therefore, we investigated
      whether NHE6 expression altered APP localization and processing in a stably
      transfected cell culture model of human APP expression. We show that co
      expression with NHE6 or treatment with the Na(+)/H(+) ionophore monensin shifted
      APP away from the trans-Golgi network into early and recycling endosomes in
      HEK293 cells. NHE6 alkalinized the endosomal lumen, similar to monensin, and
      significantly attenuated APP processing and Abeta secretion. In contrast, Abeta
      production was elevated upon NHE6 knockdown. We show that NHE6 transcript and
      protein levels are lowered in Alzheimer brains relative to control. These
      findings, taken together with emerging genetic evidence linking endosomal
      Na(+)/H(+) exchangers with Alzheimer disease, suggest that proton leak pathways
      may regulate Abeta generation and contribute to disease etiology. 

PMID- 25561735
TI  - A diverse range of bacterial and eukaryotic chitinases hydrolyzes the LacNAc
      (Galbeta1-4GlcNAc) and LacdiNAc (GalNAcbeta1-4GlcNAc) motifs found on vertebrate
      and insect cells.
AB  - There is emerging evidence that chitinases have additional functions beyond
      degrading environmental chitin, such as involvement in innate and acquired immune
      responses, tissue remodeling, fibrosis, and serving as virulence factors of
      bacterial pathogens. We have recently shown that both the human chitotriosidase
      and a chitinase from Salmonella enterica serovar Typhimurium hydrolyze LacNAc
      from Galbeta1-4GlcNAcbeta-tetramethylrhodamine (LacNAc-TMR (Galbeta1
      4GlcNAcbeta(CH2)8CONH(CH2)2NHCO-TMR)), a fluorescently labeled model substrate
      for glycans found in mammals. In this study we have examined the binding
      affinities of the Salmonella chitinase by carbohydrate microarray screening and
      found that it binds to a range of compounds, including five that contain LacNAc
      structures. We have further examined the hydrolytic specificity of this enzyme
      and chitinases from Sodalis glossinidius and Polysphondylium pallidum, which are
      phylogenetically related to the Salmonella chitinase, as well as unrelated
      chitinases from Listeria monocytogenes using the fluorescently labeled substrate
      analogs LacdiNAc-TMR (GalNAcbeta1-4GlcNAcbeta-TMR), LacNAc-TMR, and LacNAcbeta1
      6LacNAcbeta-TMR. We found that all chitinases examined hydrolyzed LacdiNAc from
      the TMR aglycone to various degrees, whereas they were less active toward LacNAc
      TMR conjugates. LacdiNAc is found in the mammalian glycome and is a common motif
      in invertebrate glycans. This substrate specificity was evident for chitinases of
      different phylogenetic origins. Three of the chitinases also hydrolyzed the beta1
      6 bond in LacNAcbeta1-6LacNAcbeta-TMR, an activity that is of potential
      importance in relation to mammalian glycans. The enzymatic affinities for these
      mammalian-like structures suggest additional functional roles of chitinases
      beyond chitin hydrolysis. 

PMID- 25561736
TI  - Protonation of the human PIEZO1 ion channel stabilizes inactivation.
AB  - PIEZO1 is a recently cloned eukaryotic cation-selective channel that opens with
      mechanical force. We found that extracellular protonation inhibits channel
      activation by ~90% by increased occupancy in the closed or the inactivated state.
      Titration between pH 6.3 and 8.3 exhibited a pK of ~6.9. The steepness of the
      titration data suggests positive cooperativity, implying the involvement of at
      least two protonation sites. Whole-cell recordings yielded results similar to
      patches, and pH 6.5 reduced whole-cell currents by >80%. The effects were
      reversible. To assess whether pH acts on the open or the inactivated state, we
      tested a double-mutant PIEZO1 that does not inactivate. Cell-attached patches and
      whole-cell currents from this mutant channel were pH-insensitive. Thus,
      protonation appears to be associated with domain(s) of the channel involved with
      inactivation. pH also did not affect mutant channels with point mutations at
      position 2456 that are known to exhibit slow inactivation. To determine whether
      the physical properties of the membrane are altered by pH and thereby affect
      channel gating, we measured patch capacitance during mechanical stimuli at pH 6.5
      and 7.3. The rate constants for changes in patch capacitance were independent of
      pH, suggesting that bilayer mechanics are not involved. In summary, low pH
      stabilizes the inactivated state. This effect may be important when channels are
      activated under pathological conditions in which the pH is reduced, such as
      during ischemia. 

PMID- 25561737
TI  - Analysis of the binding moiety mediating the interaction between monocarboxylate
      transporters and carbonic anhydrase II.
AB  - Proton-coupled monocarboxylate transporters (MCTs) mediate the exchange of high
      energy metabolites like lactate between different cells and tissues. We have
      reported previously that carbonic anhydrase II augments transport activity of
      MCT1 and MCT4 by a noncatalytic mechanism, while leaving transport activity of
      MCT2 unaltered. In the present study, we combined electrophysiological
      measurements in Xenopus oocytes and pulldown experiments to analyze the direct
      interaction between carbonic anhydrase II (CAII) and MCT1, MCT2, and MCT4,
      respectively. Transport activity of MCT2-WT, which lacks a putative CAII-binding
      site, is not augmented by CAII. However, introduction of a CAII-binding site into
      the C terminus of MCT2 resulted in CAII-mediated facilitation of MCT2 transport
      activity. Interestingly, introduction of three glutamic acid residues alone was
      not sufficient to establish a direct interaction between MCT2 and CAII, but the
      cluster had to be arranged in a fashion that allowed access to the binding moiety
      in CAII. We further demonstrate that functional interaction between MCT4 and CAII
      requires direct binding of the enzyme to the acidic cluster (431)EEE in the C
      terminus of MCT4 in a similar fashion as previously shown for binding of CAII to
      the cluster (489)EEE in the C terminus of MCT1. In CAII, binding to MCT1 and MCT4
      is mediated by a histidine residue at position 64. Taken together, our results
      suggest that facilitation of MCT transport activity by CAII requires direct
      binding between histidine 64 in CAII and a cluster of glutamic acid residues in
      the C terminus of the transporter that has to be positioned in surroundings that
      allow access to CAII. 

PMID- 25561738
TI  - Biochemical reconstitution and phylogenetic comparison of human SET1 family core
      complexes involved in histone methylation.
AB  - Mixed lineage leukemia protein-1 (MLL1) is a member of the SET1 family of histone
      H3 lysine 4 (H3K4) methyltransferases that are required for metazoan development.
      MLL1 is the best characterized human SET1 family member, which includes MLL1-4
      and SETd1A/B. MLL1 assembles with WDR5, RBBP5, ASH2L, DPY-30 (WRAD) to form the
      MLL1 core complex, which is required for H3K4 dimethylation and transcriptional
      activation. Because all SET1 family proteins interact with WRAD in vivo, it is
      hypothesized they are regulated by similar mechanisms. However, recent evidence
      suggests differences among family members that may reflect unique regulatory
      inputs in the cell. Missing is an understanding of the intrinsic enzymatic
      activities of different SET1 family complexes under standard conditions. In this
      investigation, we reconstituted each human SET1 family core complex and compared
      subunit assembly and enzymatic activities. We found that in the absence of WRAD,
      all but one SET domain catalyzes at least weak H3K4 monomethylation. In the
      presence of WRAD, all SET1 family members showed stimulated monomethyltransferase
      activity but differed in their di- and trimethylation activities. We found that
      these differences are correlated with evolutionary lineage, suggesting these
      enzyme complexes have evolved to accomplish unique tasks within metazoan genomes.
      To understand the structural basis for these differences, we employed a
      "phylogenetic scanning mutagenesis" assay and identified a cluster of amino acid
      substitutions that confer a WRAD-dependent gain-of-function dimethylation
      activity on complexes assembled with the MLL3 or Drosophila trithorax proteins.
      These results form the basis for understanding how WRAD differentially regulates
      SET1 family complexes in vivo. 

PMID- 25561739
TI  - Caveolin-1 regulates osteoclastogenesis and bone metabolism in a sex-dependent
      manner.
AB  - Lipid raft microdomains have important roles in various cellular responses.
      Caveolae are a specialized type of lipid rafts that are stabilized by oligomers
      of caveolin proteins. Here, we show that caveolin-1 (Cav-1) plays a crucial role
      in the regulation of osteoclastogenesis. We found that caveolin-1 was
      dramatically up-regulated by receptor activator of nuclear factor kappaB ligand
      (RANKL), the osteoclast differentiation factor. Knockdown of Cav-1 reduced
      osteoclastogenesis and induction of NFATc1, the master transcription factor for
      osteoclastogenesis, by RANKL. Consistent with the in vitro results, injection of
      caveolin-1 siRNA onto mice calvariae showed reduction in RANKL-induced bone
      resorption and osteoclast formation. Moreover, Cav-1(-/-) female mice had higher
      bone volume and lower osteoclast number compared with wild type mice. However,
      Cav-1(-/-) male mice had both osteoclast and osteoblast numbers higher than wild
      type mice with no difference in bone volume. The sex dependence in the effect of
      Cav-1 deficiency was partly attributed to decreased receptor activator of nuclear
      factor kappaB and increased cFms expression in osteoclast precursors of female
      and male mice, respectively. Taken together, these data demonstrate that Cav-1
      has a complicated but critical role for osteoclastogenesis. 

PMID- 25561740
TI  - A distinct triplex DNA unwinding activity of ChlR1 helicase.
AB  - Mutations in the human ChlR1 (DDX11) gene are associated with a unique genetic
      disorder known as Warsaw breakage syndrome characterized by cellular defects in
      genome maintenance. The DNA triplex helix structures that form by Hoogsteen or
      reverse Hoogsteen hydrogen bonding are examples of alternate DNA structures that
      can be a source of genomic instability. In this study, we have examined the
      ability of human ChlR1 helicase to destabilize DNA triplexes. Biochemical studies
      demonstrated that ChlR1 efficiently melted both intermolecular and intramolecular
      DNA triplex substrates in an ATP-dependent manner. Compared with other substrates
      such as replication fork and G-quadruplex DNA, triplex DNA was a preferred
      substrate for ChlR1. Also, compared with FANCJ, a helicase of the same family,
      the triplex resolving activity of ChlR1 is unique. On the other hand, the mutant
      protein from a Warsaw breakage syndrome patient failed to unwind these triplexes.
      A previously characterized triplex DNA-specific antibody (Jel 466) bound triplex
      DNA structures and inhibited ChlR1 unwinding activity. Moreover, cellular assays
      demonstrated that there were increased triplex DNA content and double-stranded
      breaks in ChlR1-depleted cells, but not in FANCJ(-/-) cells, when cells were
      treated with a triplex stabilizing compound benzoquinoquinoxaline, suggesting
      that ChlR1 melting of triple-helix structures is distinctive and physiologically
      important to defend genome integrity. On the basis of our results, we conclude
      that the abundance of ChlR1 known to exist in vivo is likely to be a strong
      deterrent to the stability of triplexes that can potentially form in the human
      genome. 

PMID- 25561742
TI  - Regulation of the temperature-dependent activation of transient receptor
      potential vanilloid 1 (TRPV1) by phospholipids in planar lipid bilayers.
AB  - TRPV1 (transient receptor potential vanilloid 1) proteins are heat-activated
      nonselective cation channels. TRPV1 channels are polymodal in their function and
      exhibit multifaceted regulation with various molecular compounds. In this regard,
      phosphoinositides, particularly phosphatidylinositol 4,5-bisphosphate and
      phosphatidylinositol 4-phosphate, are important channel regulators. However,
      their effects on TRPV1 channel activity have not been conclusively determined. To
      characterize temperature-induced activation of TRPV1 in the presence of different
      phospholipids, we purified the TRPV1 protein from HEK-293 cells and incorporated
      it into planar lipid bilayers. In the presence of 2.5 MUm phosphatidylinositol
      4,5-bisphosphate, TRPV1 channels demonstrated rapid activation at 33-39  degrees
      C and achieved full channel opening at 42  degrees C. At this temperature range,
      TRPV1 heat activation exhibited steep temperature dependence (temperature
      coefficient (Q10) of 18), and the channel openings were accompanied by large
      changes in entropy and enthalpy, suggesting a substantial conformation change. At
      a similar temperature range, another phosphoinositide, phosphatidylinositol 4
      phosphate, also potentiated heat activation of TRPV1, but with much lower
      efficiency. Negatively charged phosphatidylglycerol could also induce heat
      activation of TRPV1 channels, although with a small-conductance state. Our data
      demonstrate that phospholipids, specifically phosphoinositides, are important
      regulators of TRPV1 and are required for heat-induced channel activity. 

PMID- 25561741
TI  - Novel regulation of Ski protein stability and endosomal sorting by actin
      cytoskeleton dynamics in hepatocytes.
AB  - TGF-beta-induced antimitotic signals are highly regulated during cell
      proliferation under normal and pathological conditions, such as liver
      regeneration and cancer. Up-regulation of the transcriptional cofactors Ski and
      SnoN during liver regeneration may favor hepatocyte proliferation by inhibiting
      TGF-beta signals. In this study, we found a novel mechanism that regulates Ski
      protein stability through TGF-beta and G protein-coupled receptor (GPCR)
      signaling. Ski protein is distributed between the nucleus and cytoplasm of normal
      hepatocytes, and the molecular mechanisms controlling Ski protein stability
      involve the participation of actin cytoskeleton dynamics. Cytoplasmic Ski is
      partially associated with actin and localized in cholesterol-rich vesicles. Ski
      protein stability is decreased by TGF-beta/Smads, GPCR/Rho signals, and actin
      polymerization, whereas GPCR/cAMP signals and actin depolymerization promote Ski
      protein stability. In conclusion, TGF-beta and GPCR signals differentially
      regulate Ski protein stability and sorting in hepatocytes, and this cross-talk
      may occur during liver regeneration. 

PMID- 25561743
TI  - A novel post-translational modification of nucleolin, SUMOylation at Lys-294,
      mediates arsenite-induced cell death by regulating gadd45alpha mRNA stability.
AB  - Nucleolin is a ubiquitously expressed protein and participates in many important
      biological processes, such as cell cycle regulation and ribosomal biogenesis. The
      activity of nucleolin is regulated by intracellular localization and post
      translational modifications, including phosphorylation, methylation, and ADP
      ribosylation. Small ubiquitin-like modifier (SUMO) is a category of recently
      verified forms of post-translational modifications and exerts various effects on
      the target proteins. In the studies reported here, we discovered SUMOylational
      modification of human nucleolin protein at Lys-294, which facilitated the mRNA
      binding property of nucleolin by maintaining its nuclear localization. In
      response to arsenic exposure, nucleolin-SUMO was induced and promoted its binding
      with gadd45alpha mRNA, which increased gadd45alpha mRNA stability and protein
      expression, subsequently causing GADD45alpha-mediated cell death. On the other
      hand, ectopic expression of Mn-SOD attenuated the arsenite-generated superoxide
      radical level, abrogated nucleolin-SUMO, and in turn inhibited arsenite-induced
      apoptosis by reducing GADD45alpha expression. Collectively, our results for the
      first time demonstrate that nucleolin-SUMO at K294R plays a critical role in its
      nucleus sequestration and gadd45alpha mRNA binding activity. This novel
      biological function of nucleolin is distinct from its conventional role as a
      proto-oncogene. Therefore, our findings here not only reveal a new modification
      of nucleolin protein and its novel functional paradigm in mRNA metabolism but
      also expand our understanding of the dichotomous roles of nucleolin in terms of
      cancer development, which are dependent on multiple intracellular conditions and
      consequently the appropriate regulations of its modifications, including
      SUMOylation. 

PMID- 25561746
TI  - Hydrocortisone for adrenal insufficiency.

PMID- 25561747
TI  - Reimagining the Pipeline: Advancing STEM Diversity, Persistence, and Success.
AB  - Achieving trainee diversity in science, technology, engineering, and mathematics
      is rapidly becoming a challenge faced by many nations. Success in this area
      ensures the availability of a workforce capable of engaging in scientific
      practices that will promote increased production capacity and creativity and will
      preserve global scientific competitiveness. The near-term vision of achieving
      this goal is within reach and will capitalize on the growing numbers of
      underrepresented minority groups in the population. Although many nations have
      had remarkable histories as leaders in science and technology, few have
      simultaneously struggled with the challenge of meeting the educational and
      training needs of underrepresented groups. In this article, we share strategies
      for building the agency of the scientific community to achieve greater diversity
      by highlighting four key action areas: (1) aligning institutional culture and
      climate; (2) building interinstitutional partnerships; (3) building and
      sustaining critical mass; and (4) ensuring, rewarding, and maximizing faculty
      involvement.

PMID- 25561744
TI  - How informative is the mouse for human gut microbiota research?
AB  - The microbiota of the human gut is gaining broad attention owing to its
      association with a wide range of diseases, ranging from metabolic disorders (e.g.
      obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel
      disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g.
      autism). Having been increasingly used in biomedical research, mice have become
      the model of choice for most studies in this emerging field. Mouse models allow
      perturbations in gut microbiota to be studied in a controlled experimental setup,
      and thus help in assessing causality of the complex host-microbiota interactions
      and in developing mechanistic hypotheses. However, pitfalls should be considered
      when translating gut microbiome research results from mouse models to humans. In
      this Special Article, we discuss the intrinsic similarities and differences that
      exist between the two systems, and compare the human and murine core gut
      microbiota based on a meta-analysis of currently available datasets. Finally, we
      discuss the external factors that influence the capability of mouse models to
      recapitulate the gut microbiota shifts associated with human diseases, and
      investigate which alternative model systems exist for gut microbiota research. 

PMID- 25561748
TI  - Patellar instability - Changing beliefs and current trends.

PMID- 25561749
TI  - FE analysis of stress and displacements occurring in the bony chain of leg.
AB  - AIMS: The aim of this study was to assess how the stress shielding can influence
      the integrity and resistance of bones. METHODS: With this purpose a complete FE
      model of the human leg was realised. A load of 700 N has been applied at the top
      of pelvis and the feet, at the tip, was rigidly fixed. RESULTS: Obtained results
      reveal interesting consequences deriving by taking into account the complete bony
      chain. CONCLUSION: A comparison among the literature data and our models can
      furnish a complete vision of the global spreading of the forces along the various
      bony components.

PMID- 25561745
TI  - Targets, models and challenges in osteoarthritis research.
AB  - Osteoarthritis is a chronic degenerative disorder of the joint and represents one
      of the most common diseases worldwide. Its prevalence and severity are increasing
      owing to aging of the population, but treatment options remain largely limited to
      painkillers and anti-inflammatory drugs, which only provide symptomatic relief.
      In the late stages of the disease, surgical interventions are often necessary to
      partially restore joint function. Although the focus of osteoarthritis research
      has been originally on the articular cartilage, novel findings are now pointing
      to osteoarthritis as a disease of the whole joint, in which failure of different
      joint components can occur. In this Review, we summarize recent progress in the
      field, including data from novel 'omics' technologies and from a number of
      preclinical and clinical trials. We describe different in vitro and in vivo
      systems that can be used to study molecules, pathways and cells that are involved
      in osteoarthritis. We illustrate that a comprehensive and multisystem approach is
      necessary to understand the complexity and heterogeneity of the disease and to
      better guide the development of novel therapeutic strategies for osteoarthritis. 

PMID- 25561750
TI  - Early complications of primary total hip arthroplasty in the supine position with
      a modified Watson-Jones anterolateral approach.
AB  - BACKGROUND: For total hip arthroplasty (THA), minimally invasive surgery (MIS)
      has been developed to reduce incision length, muscle damage, and a shorter
      hospital stay. However, reduced exposure of anatomical landmarks may result in
      technical errors and inferior implant survivorships. The aim of this study was to
      report the short-term results and clinical complications of primary MIS THA in
      the supine position. METHODS: A consecutive series of 103 patients who underwent
      MIS cementless THA with a modified Watson-Jones anterolateral approach (AL) were
      enrolled. Outcomes data were reviewed at a minimum of 12 months following the
      procedure. Clinical evaluations were made using the Merle d'Aubigne and Postel
      hip score. The results of these procedures were retrospectively compared with
      those of a historical series of 98 total hip arthroplasties that had been
      performed by the same surgeon with use of a posterolateral approach (PL).
      RESULTS: In the MIS AL THA group, intraoperative fracture was observed in 6 hips;
      3 in greater trochanter and 3 in calcar femoral. One hip was subjected to
      irrigation because of postoperative infection was suspected. In the PL group,
      intraoperative fracture was demonstrated in 4 hips in calcar femoral. No
      postoperative dislocation and no pulmonary embolism or nerve paralysis was
      observed in both groups. CONCLUSIONS: The MIS AL THA did not show a clinically
      relevant superior outcome compared with the PL THA. When performing MIS AL THA,
      special attention should pay for prevention of greater trochanter fracture.

PMID- 25561752
TI  - Verification of hip reduction using anterior ultrasound scanning during Pavlik
      harness treatment of developmental dysplasia of the hip.
AB  - AIM: Ultrasound scanning (USS) is used for diagnosis and surveillance in
      developmental dysplasia of the hip (DDH). Lateral coronal scanning is performed
      with the hip flexed, in neutral adduction. In this position an unstable hip may
      dislocate, failing to demonstrate a reducible hip, leading to abandonment of
      harness treatment. Anterior ultrasound permits imaging of the flexed abducted hip
      in harness. This study evaluates the role of anterior & lateral USS in
      determining duration of treatment and reduction in DDH. METHOD: Between 1997 &
      2010, 233 patients requiring harness treatment received lateral USS, with
      dislocated & dysplastic hips re-imaged fortnightly. From 2005, anterior USS was
      used additionally to assess reduction in harness. RESULTS: One-hundred and
      eighteen patients (167 hips) received lateral USS, 115 (160 hips) received both.
      In the lateral cohort, 103 (140 hips) were treated successfully, mean duration
      66.2 days (95% CI 60.2-72.1), with 15 (26 hips) failures (15.5%), mean 30 (CI 95%
      19.3-40.6). In the anterior cohort, 107 (150 hips) were treated successfully,
      mean 53.3 (95% CI 49.8-56.7), with 8 (10 hips) failures (6.25%), mean 35.3 (CI
      95% 25.5-44.9). Children receiving an anterior USS had a shorter duration of
      treatment (p = 0.011) and no difference in failures (p = 0.21). CONCLUSIONS: A
      reduced duration of treatment for Graf 3 hips was observed. Anterior ultrasound
      allows earlier recognition of hips that fail to stabilize, via two observed modes
      of failure; failure of hip reduction and failure to stabilize after reduction.

PMID- 25561751
TI  - Mid-term clinical results of total hip arthroplasty using a Wagner standard cup
      for dysplastic hip.
AB  - BACKGROUND: The outcome of cementless total hip arthroplasty depends on many
      factors. We must not forget fundamental things those are design of outer surface
      of the component, that leads bone ingrowth into the prosthesis, better initial
      stability, and better insertional techniques. The purpose of this study was to
      review our experience with metal-on-metal total hip arthroplasty with a Wagner
      standard cup for patients who had acetabular dysplasia. PATIENTS AND METHODS:
      Fifty-four patients with 55 hips underwent primary metal-on-metal total hip
      arthroplasty (Metasul prosthesis) with a Wagner standard cup (44-48 mm in outer
      diameter) and were followed for a minimum of 10 years. All patients received the
      same type of cementless femoral component (Natural hip stem) and femoral head (28
      mm in diameter). RESULTS: Seventeen of the 55 Wagner standard cups (30.9%) showed
      aseptic loosening over a mean period of 3.6 years after surgery, and there were
      no bone anchors on the outer surface of the 16 retrieved cups. CONCLUSION: From
      our experience, the small Wagner standard cup does not achieve sufficient
      osteointegration and we do not recommend the use of this cup, especially for
      patients with acetabular dysplasia and/or those with a small stature.

PMID- 25561753
TI  - Symptoms of discoid lateral menisci.
AB  - PURPOSE: This study aims to determine the symptoms of the patients with discoid
      lateral meniscus. METHODS: We prospectively collected cases of the knees with
      discoid lateral meniscus. Twenty patients (7 female, 13 male) admitted between
      January 2012 and February 2014 were enrolled in this study. The mean age of the
      patients was 34 years (range 28-40). RESULTS: The identified symptoms of a
      discoid lateral meniscus were "pain, stiffness, popping of the knee, feeling that
      the knee is "giving way", inability to fully extend (straighten) the knee".
      Thirteen patients (65%) had pain, 11 (55%) had popping of the knee, 4 (20%) had
      stiffness, 2 (10%) had "giving way" feeling, and 1 (5%) had inability to fully
      extend the knee. These symptoms did not prevent any patient's daily activities.
      No patients required surgical treatment. CONCLUSIONS: Pain and popping of the
      knee were the most common symptoms in patients with a discoid lateral meniscus.
      The other symptoms were stiffness, feeling that the knee is "giving way", and
      inability to fully extend the knee, respectively. No symptoms had been required
      surgical treatment.

PMID- 25561754
TI  - Simultaneous femoral and tibial lengthening in combined congenital complete
      fibular hemimelia and congenital short femur using Ilizarov ring external
      fixator.
AB  - PURPOSE: The combination of fibular hemimelia with congenital short femur worsens
      the limb length discrepancy which requires extensive femoral and tibial
      lengthening. PATIENTS AND METHODS: Eight patients having unilateral lower
      extremity shortening presented to the National Institute of Neuromotor System,
      Egypt, between September 2008 and September 2010 and underwent single session
      femoral and tibial lengthening using Ilizarov ring external fixator technique.
      Consolidation of the femoral and tibial required length gain was evident in the
      radiographic follow-up. CONCLUSION: Extensive limb length discrepancy can be
      managed by simultaneous femoral and tibial lengthening. LEVEL OF EVIDENCE: The
      study is type IV clinical evidence.

PMID- 25561755
TI  - Localized naviculocuneiform arthrodesis combined with osteosynthesis of fracture
      nonunion of the tarsal navicular bone using a locked plating system.
AB  - AIMS: Navicular fracture is still challenging disorder to treat because there is
      a risk of nonunion, avascular necrosis and symptomatic osteoarthritis. PATIENTS
      METHODS AND RESULTS: A 40-year-old woman with an ununited fracture of the tarsal
      navicular bone was treated with localized naviculocuneiform arthrodesis
      (arthrodesis of the navicular, the middle cuneiform, and the lateral cuneiform).
      Fusion with the navicular, the middle cuneiform, and the lateral cuneiform as
      well as union of fracture of the navicular was confirmed on the radiographs.
      CONCLUSION: Localized naviculocuneiform arthrodesis using a locked plating system
      is one of the options to treat nonunion of the navicular bone.

PMID- 25561756
TI  - Complete rupture of the popliteal artery complicating high tibial osteotomy.
AB  - We present two cases of high tibial osteotomies performed at our institution.
      Both cases were complicated with the immediate postoperative occurrence of an
      ischaemic syndrome of the lower leg. Urgent diagnostics revealed a complete
      rupture of the popliteal artery that required re-operation and a vascular repair.
      Although neurovascular complications during high tibial osteotomies are rare the
      awareness of this potentially catastrophic complication should be present when
      performing this common procedure. All precautions to minimize the harm to the
      neurovascular bundle should be put into practice. A summary of the surgical
      precautions is presented and discussed in this paper. 

PMID- 25561757
TI  - Pseudomyogenic (Epithelioid sarcoma-like) hemangioendothelioma with bone
      invasion.
AB  - AIM: Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma is a rare
      local aggressive vascular tumor. Herein we present a 54-year-old male patient
      with a tumor on his index finger. CASE: The patient presented with a 1-year
      history of pain and swelling that progressively exacerbated. Bone invasion was
      observed on the middle phalanx via direct radiography. Histopathological
      examination findings were compatible with epithelioid sarcoma-like
      hemangioendothelioma. CONCLUSION: To the best of our knowledge is the first case
      report of epithelioid sarcoma-like hemangioendothelioma with bone invasion.

PMID- 25561758
TI  - New 'multi-omics' approach and its contribution to hepatocellular carcinoma in
      China.

PMID- 25561759
TI  - Quantitative index calculated by (99m)Tc-GSA scintigraphy.
AB  - (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy is useful to evaluate
      hepatic function and hepatic functional reserve. A reliable SPECT and CT
      integrated system is now commercially available. Using this system, we can obtain
      (99m)Tc-GSA SPECT/CT fused imaging with a small registration error. Therefore,
      the (99m)Tc-GSA scintigraphy techniques prove more useful in clinical practice
      than have been previously reported. In the latest Annals of Surgical Oncology on
      Oct 2014, the uptake index (UI) values calculated from (99m)Tc-GSA scintigraphy
      are reported to be useful for predicting the functional reserve of the future
      remnant liver. In this paper, we describe the usefulness of (99m)Tc-GSA
      scintigraphy as well as some cautions that are necessary as regards using the
      system. 

PMID- 25561760
TI  - Use of endoscopic ultrasound-based techniques in tumor of the guts and beyond.

PMID- 25561761
TI  - Comparison of three mathematical prediction models in patients with a solitary
      pulmonary nodule.
AB  - BACKGROUND: Effective methods for managing patients with solitary pulmonary
      nodules (SPNs) depend critically on the predictive probability of malignancy.
      METHODS: Between July 2009 and June 2011, data on gender, age, cancer history,
      tumor familial history, smoking status, tumor location, nodule size, spiculation,
      calcification, the tumor border, and the final pathological diagnosis were
      collected retrospectively from 154 surgical patients with an SPN measuring 3-30
      mm. Each final diagnosis was compared with the probability calculated by three
      predicted models-the Mayo, VA, and Peking University (PU) models. The accuracy of
      each model was assessed using area under the receiver operating characteristics
      (ROC) and calibration curves. RESULTS: The area under the ROC curve of the PU
      model [0.800; 95% confidence interval (CI): 0.708-0.891] was higher than that of
      the Mayo model (0.753; 95% CI: 0.650-0.857) or VA model (0.728; 95% CI: 0.623
      0.833); however, this finding was not statistically significant. To varying
      degrees, calibration curves showed that all three models overestimated
      malignancy. CONCLUSIONS: The three predicted models have similar accuracy for
      prediction of SPN malignancy, although the accuracy is not sufficient. For
      Chinese patients, the PU model may has greater predictive power.

PMID- 25561762
TI  - Application of CUSA Excel ultrasonic aspiration system in resection of skull base
      meningiomas.
AB  - BACKGROUND: Here, we introduced our short experience on the application of a new
      CUSA Excel ultrasonic aspiration system, which was provided by Integra
      Lifesciences corporation, in skull base meningiomas resection. METHODS: Ten
      patients with anterior, middle skull base and sphenoid ridge meningioma were
      operated using the CUSA Excel ultrasonic aspiration system at the Neurosurgery
      Department of Shanghai Huashan Hospital from August 2014 to October 2014. There
      were six male and four female patients, aged from 38 to 61 years old (the mean
      age was 48.5 years old). Five cases with tumor located at anterior skull base,
      three cases with tumor on middle skull base, and two cases with tumor on sphenoid
      ridge. RESULTS: All the patents received total resection of meningiomas with the
      help of this new tool, and the critical brain vessels and nerves were preserved
      during operations. All the patients recovered well after operation. CONCLUSIONS:
      This new CUSA Excel ultrasonic aspiration system has the advantage of preserving
      vital brain arteries and cranial nerves during skull base meningioma resection,
      which is very important for skull base tumor operations. This key step would
      ensure a well prognosis for patients. We hope the neurosurgeons would benefit
      from this kind of technique.

PMID- 25561763
TI  - Knockdown of HMGB1 improves apoptosis and suppresses proliferation and invasion
      of glioma cells.
AB  - BACKGROUND: The purposes of this study were to explore the effects of high
      mobility group protein box 1 (HMGB1) gene on the growth, proliferation,
      apoptosis, invasion, and metastasis of glioma cells, with an attempt to provide
      potential therapeutic targets for the treatment of glioma. METHODS: The
      expressions of HMGB1 in glioma cells (U251, U-87MG and LN-18) and one control
      cell line (SVG p12) were detected by real time PCR and Western blotting,
      respectively. Then, the effects of HMGB1 on the biological behaviors of glioma
      cells were detected: the expression of HMGB1 in human glioma cell lines U251 and
      U-87MG were suppressed using RNAi technique, then the influences of HMGB1 on the
      viability, cycle, apoptosis, and invasion abilities of U251 and U-87MG cells were
      analyzed using in a Transwell invasion chamber. Also, the effects of HMGB1 on the
      expressions of cyclin D1, Bax, Bcl-2, and MMP 9 were detected. RESULTS: As shown
      by real-time PCR and Western blotting, the expression of HMGB1 significantly
      increased in glioma cells (U251, U-87MG, and LN-18) in comparison with the
      control cell line (SVG p12); the vitality, proliferation and invasive
      capabilities of U251 and U-87MG cells in the HMGB1 siRNA-transfected group were
      significantly lower than those in the blank control group and negative control
      (NC) siRNA group (P<0.05) but showed no significant difference between the blank
      control group and NC siRNA group. The percentage of apoptotic U251 and U-87MG
      cells was significantly higher in the HMGB1 siRNA-transfected group than in the
      blank control group and NC siRNA group (P<0.05) but was similar between the
      latter two groups. The HMGB1 siRNA-transfected group had significantly lower
      expression levels of Cyclin D1, Bcl-2, and MMP-9 protein in U251 and U-87MG cells
      and significantly higher expression of Bax protein than in the blank control
      group and NC siRNA group (P<0.05); the expression profiles of cyclin D1, Bax, Bcl
      2, and MMP 9 showed no significant change in both blank control group and NC
      siRNA group. CONCLUSIONS: HMGB1 gene may promote the proliferation and migration
      of glioma cells and suppress its effects of apoptosis. Inhibition of the
      expression of HMGB1 gene can suppress the proliferation and migration of glioma
      cells and promote their apoptosis. Our observations provided a new target for
      intervention and treatment of glioma.

PMID- 25561764
TI  - Expression of VEGFR2 and NRP-1 in non-small cell lung cancer and their clinical
      significance.
AB  - OBJECTIVE: Vascular-targeted therapy is gradually becoming more appealing for
      patients with lung cancer. It is unclear whether vascular endothelial growth
      factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) can be biomarkers for
      clinical treatment. We aimed to investigate the expression levels of VEGFR2 and
      NRP-1 in human non-small cell lung cancer (NSCLC) and their clinical significance
      by observing patient prognosis. METHODS: VEGFR2 and NRP-1 were assessed by
      immunohistochemistry (IHC) in 40 patients with NSCLC and in 10 patients with
      benign lesions of lung; kinase insert domain receptor (KDR) and NRP-1 copy number
      gain (CNG) was assessed by fluorescence in situ hybridization (FISH). The
      distributions of overall survival (OS) and progression-free survival (PFS) were
      estimated using the Kaplan-Meier method and compared between groups by log-rank
      test. RESULTS: Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and
      55%, respectively. KDR and NRP-1 CNG (+) were detected in 32.5% and 30% of
      tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were
      significantly different than in the control tissue (chi(2)=11.22, P=0.001;
      chi(2)=9.82, P=0.001, respectively); similar results were obtained using CNGs
      (chi(2)=4.39, P=0.036; chi(2)=3.95, P=0.046, respectively). Statistically
      significant correlations were observed with histological grade, clinical TNM
      stage and the lymph node status (P<0.05), but not age, gender or pathology type
      (P>0.05). VEGFR2 showed a strong correlation with NRP-1 (Rs=0.68, P=0.00);
      similar results were observed with KDR and NRP-1 CNG (Rs=0.32, P=0.04).
      Significant differences in OS and PFS were observed between the groups with
      higher VEGFR2 and NRP-1 and those with lower expression (P<0.05). CONCLUSIONS:
      According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can
      conclude that they play a key role in NSCLC occurrence, development and
      metastasis and are associated with patient prognosis (P<0.05 for OS and PFS).
      This information will be beneficial for clinical anti-angiogenic treatment in
      NSCLC.

PMID- 25561765
TI  - Impact of jejunostomy during esophagectomy for cancer on health related quality
      of life.
AB  - BACKGROUND: The aim of this study was to evaluate the impact of jejunostomy
      during esophagectomy for cancer on postoperative health-related quality of life
      (HRQL). METHODS: We evaluate all consecutive patients who underwent esophagectomy
      for cancer at the surgical oncology unit of the Veneto Institute of Oncology (IOV
      IRCCS) between January 2008 and March 2014. The primary outcome was HRQL, which
      was assessed using nine scales of EORTC C30 and OES18 questionnaires. General
      linear models were estimated to evaluate mean score difference (MD) of each
      selected scale in patients with and without jejunostomy, adjusting for clinically
      relevant confounders. The secondary outcomes were morbidity, hospital stay,
      postoperative weight loss and postoperative albumin impairment. RESULTS:
      Jejunostomy was performed in 40 on 109 patients (41.3%) who participated in
      quality of life investigation. A clinically and statistically significantly worse
      eating at admission (P=0.009) became not clinically significant at 3 months after
      surgery (MD =9.1). Jejunostomy was associated to clinically and statistically
      significantly poorer emotional function (EF) at 3 months after surgery (MD =
      15.6; P=0.04). Hospital stay was longer in jejunostomy group (median, 20 vs. 17
      days, P=0.02). CONCLUSIONS: In our series patients who had a jejunostomy during
      esophagectomy had been selected for their risk for postoperative complication.
      However, their postoperative outcome was actually similar compared to those
      without jejunostomy. Nevertheless, jejunostomy was associated to clinically and
      statistically significantly poorer EF at 3 months after surgery. Therefore,
      patient candidate to esophagectomy and feeding jejunostomy should receive
      additional psychological support.

PMID- 25561766
TI  - Factors contributing to lymph node occult metastasis in supraglottic laryngeal
      carcinoma cT2-T4 N0M0 and metastasis predictive equation.
AB  - OBJECTIVE: To investigate factors that contribute to lymph node metastasis (LNM)
      from clinical cT2-T4 N0M0 (cN0) supraglottic laryngeal carcinoma (SLC), and to
      predict the risk of occult metastasis before surgery. METHODS: A total of 121
      patients who received surgery were retrospectively analyzed. Relevant factors
      regarding cervical LNM were analyzed. Multivariate analyses were conducted to
      predict the region where the metastasis occurred and prognosis. RESULTS: The
      overall metastatic rate of cN0 SLC was 28.1%. Metastatic rates were 15.4%, 32.5%
      and 35.7% for T2, T3 and T4, respectively. Metastatic rates for SLC levels II,
      III and IV were 19.6%, 17.2% and 3.6%, respectively. A regression equation was
      formulated to predict the probability of metastasis in cN0 SLC as follows: Pn=e((
      3.874+0.749T3+1.154T4+1.935P1+1.750P2))/[1+e((
      3.874+0.749T3+1.154T4+1.935P1+1.750P2))]. Approximately 0.2% of patients
      experienced LNM with no recurrence of laryngeal cancer. Comparison of the
      intergroup survival curves between patients with and without LNM indicated a
      statistically significant difference (P=0.029). CONCLUSIONS: Cervical lymph node
      metastatic rates tended to increase in tandem with T stage in patients with LNM
      in cN0 SLC, and neck dissection is advised for these patients. Moreover, cervical
      LNM in cN0 SLC showed a sequential pattern and may be predicted.

PMID- 25561767
TI  - Efficacy of capecitabine-based combination therapy and single-agent capecitabine
      maintenance therapy in patients with metastatic breast cancer.
AB  - OBJECTIVE: The purpose of this study was to observe the efficacy and toxicities
      of capecitabine-based chemotherapy and capecitabine monotherapy as maintenance
      therapy in the treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS:
      A total of 98 MBC patients were treated with capecitabine combined with
      vinorelbine (NX). RESULTS: The median number of treatment was 6 cycles (1-7
      cycles). There were two cases of complete remission (CR), 58 partial remission,
      27 stable disease (SD), 11 progression disease. The overall response rate (ORR)
      (CR + PR) was 61.2%. The clinical benefit rate (CBR) was 75.5%. Fifty of
      effective patients received with capecitabine monotherapy as maintenance therapy.
      The ORR (CR + PR) was 4%. The CBR was 48%. The median progression-free survival
      (PFS) was 12 months. In maintenance therapy or not, the median post metastasis
      survival rate (MSR) was 63 and 28 months, respectively. In the combination
      therapy group, the major grade 3/4 toxicities included hand-foot syndrome (3.1%),
      skin pigmentation (2.0%), diarrhoea and abdominal distension (5.1%), stomatitis
      (1.0%), and leukopenia (20.4%). CONCLUSIONS: Capecitabine-based combination
      therapy and single-agent capecitabine maintenance therapy were well tolerated and
      effective to MBC.

PMID- 25561768
TI  - Distribution and drug resistance of pathogenic bacteria isolated from cancer
      hospital in 2013.
AB  - OBJECTIVE: To understand distribution and drug resistance of pathogenic bacteria
      from a specialized cancer hospital in 2013 in order to provide a basis for
      rational clinical antimicrobial agents. METHODS: Pathogenic bacteria
      identification and drug sensitivity tests were performed with a VITEK 2 compact
      automatic identification system and data were analyzed using WHONET5.6 software.
      RESULTS: Of the 1,378 strains tested, 980 were Gram-negative bacilli, accounting
      for 71.1%, in which Klebsiella pneumonia, Escherichia coli and Pseudomonas
      aeruginosa were the dominant strains. We found 328 Gram-positive coccus,
      accounting for 23.8%, in which the amount of Staphylococcus aureus was the
      highest. We identified 46 fungi, accounting for 4.1%. According to the
      departmental distribution within the hospital, the surgical departments isolated
      the major strains, accounting for 49.7%. According to disease types, lung cancer,
      intestinal cancer and esophagus cancer were the top three, accounting for 20.9%,
      17.3% and 14.2%, respectively. No strains were resistant to imipenem, ertapenem
      or vancomycin. CONCLUSIONS: Pathogenic bacteria isolated from the specialized
      cancer hospital have different resistance rates compared to commonly used
      antimicrobial agents; therefore antimicrobial agents to reduce the morbidity and
      mortality of infections should be used.

PMID- 25561769
TI  - Efficacy of third-line pemetrexed monotherapy versus pemetrexed combination with
      bevacizumab in patients with advanced EGFR mutation-positive lung adenocarcinoma.
AB  - OBJECTIVE: The purposes of this study were to observe the effects of different
      treatment strategies, including third-line pemetrexed alone versus its
      combination with bevacizumab, in patients with advanced epidermal growth factor
      receptor (EGFR) mutation-positive lung adenocarcinoma, and to analyze the effects
      of the different medication orders of first- and second-line drugs on third-line
      efficacy. PATIENTS AND METHODS: One hundred and sixteen cases of patients with
      EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or
      in combination with bevacizumab between March 2010 and March 2014 at Guangzhou
      Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou
      Medical University were analyzed retrospectively. Additionally, all the patients
      were treated with first-line gemcitabine and cisplatin (GP) chemotherapy and
      second-line EGFR tyrosine kinase inhibitor (TKI) or with first-line EGFR-TKI and
      second-line GP chemotherapy. RESULTS: The median survival of 61 cases with third
      line pemetrexed monotherapy was 36.22 months, the median survival time of 55
      cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was
      a significant difference in survival time between the two groups (P=0.04).
      Subgroup analysis revealed that among the 55 cases with third-line bevacizumab
      plus pemetrexed treatment, the median survival of 29 patients with first-line GP
      and second-line EGFR-TKI was 42.80 months, while the median survival of 26
      patients with first-line EGFR-TKI and second-line GP was only 34.46 months;
      additionally, there was a significant difference in the survival time between the
      two subgroups (P=0.001). Among 61 cases with third-line pemetrexed treatment, the
      median survival of 34 patients with first-line GP and second-line EGFR-TKI was
      38.72 months, while the median survival of 27 patients with first-line EGFR-TKI
      and second-line GP was only 32.94 months; the survival time of the two subgroups
      was significantly different (P=0.001). CONCLUSIONS: Regardless of the order of
      the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus
      bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line
      therapy in patients with advanced EGFR-positive lung adenocarcinoma. However,
      this strategy is worth further investigation in prospective studies.

PMID- 25561770
TI  - Downregulation of serum miR-17 and miR-106b levels in gastric cancer and benign
      gastric diseases.
AB  - Altered microRNA (miRNA) associated with gastric cancer (GC) development and miR
      17 and miR-106b were differentially expressed in GC tissues. This study detected
      serum levels of miR-17 and miR-106b expression in GC, benign gastric disease
      (BGD) and healthy controls to assess them as tumor markers for GC. Serum samples
      from 40 GC, 32 BGD (10 gastric ulcer, 14 gastric polyps, and 8 gastric ulcer with
      polyps) and 36 healthy individuals were subjected to quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) analysis of miR-17 and miR-106b
      expression. The data showed that the serum levels of miR-17 and miR-106b were
      significantly reduced in healthy individuals and BGD patients compared to GC
      patients. There was a significant association of miR-17 and miR-106b expression
      with age, but not with other clinicopathological features, such as gender, tumor
      differentiation, stage and lymphatic metastasis. Further analysis showed that, in
      discriminating GC patients from healthy controls, miR-17 could yield a receiver
      operating characteristic (ROC) area under the curve (AUC) of 0.879 with 80.6%
      sensitivity and 87.5% specificity and miR-106b could yield an AUC of 0.856 with
      75.0% sensitivity and 92.5% specificity. The combined AUC of miR-17 and miR-106b
      was 0.913 with 83.3% sensitivity and 87.5% specificity. Collectively, these data
      suggest that detection of serum miR-17 and miR-106b levels should be further
      evaluated as novel non-invasive biomarkers in early GC detection and surveillance
      of disease progression. 

PMID- 25561771
TI  - A path for diagnosis and therapy of colon cancer: a continuous quality
      improvement.
AB  - OBJECTIVE: Prognosis of colorectal cancer strongly depends on stage at diagnosis,
      which can be cured in most cases at an early stage. The results were supported by
      different screening programmes. Few data concerning analysis of different phases
      of Colorectal Cancer Program were reported in literature. The aim of this study
      is to analyze "step by step", from a longitudinal type, the Colorectal Cancer
      Program, active at our Institution, verifying compliance with standards of care.
      METHODS: We compared two different populations during the same period: patients
      referring to our Clinical Oncology Unit coming from Regional Colorectal Cancer
      Screening Program and the other population that was not in any Colorectal Cancer
      Program. RESULTS: Considering patients from the Regional Colorectal Cancer
      Screening Program (19 patients, corresponding to 24.0% of the general case
      study), 3 (15.8%) were deceased and 16 (84.2%) were alive without evidence of the
      disease (NED). Concerning patients that are not coming from Regional Colorectal
      Cancer Screening Program (61 patients, corresponding to 76.0% of the general case
      study), 9 (14.8%) were deceased, 43 (70.5%) were NED, 8 (13.1%) were alive with
      metastases and 1 (1.6%) was lost during follow-up (PFU). CONCLUSIONS: On the
      basis of this experience, we concluded for high-quality care for both
      populations. Any critical point should be carefully analyzed in order to
      implement quality of care.

PMID- 25561773
TI  - Next generation sequencing, inter-tumor heterogeneity and prognosis of hepatitis
      B related hepatocellular carcinoma.

PMID- 25561772
TI  - Endoscopic ultrasonography: an advancing option with duality in both diagnosis
      and treatment of gastrointestinal oncology.
AB  - Since their introduction into the clinical practices in 1980s, techniques of
      endoscopic ultrasonography (EUS) have been rapidly developing and are now in
      widespread use in gastrointestinal oncology. Evolving from the classical option,
      EUS today has been much innovated with addition of a variety of novel ideation
      which makes it a powerful tool with encouraging duality for both diagnostic and
      therapeutic purposes. There is a dire need for physicians in this field to
      understand the status quo of EUS as related to the management and detection of
      gastrointestinal tumors, which is globally reviewed in this paper. 

PMID- 25561774
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration: unraveling
      myths of mass in the chest.

PMID- 25561775
TI  - Laparoscopic left liver lobectomy for hepatocellular carcinoma in a cirrhotic
      patient: a video report.
AB  - We present a video case of a 51-year-old man admitted to our surgical and liver
      transplantation unit for hepatocellular cancer (HCC). Patient has a HCV cirrhosis
      with portal hypertension and esophageal varices F1. Child Pugh score was B7 and
      model of end staged liver disease (MELD) was 11. Body mass index (BMI) was 26.7
      and ASA score was 2. No previous abdominal surgery. According with our
      multidisciplinary group we suggest a laparoscopic left lobectomy for the patient.
      Pringle manoeuvre was not performed. Operation time was 193 min and blood loss
      estimation was 100 cc. No transfusion was required. Post-operative course was
      uneventful, grade I of Clavien-Dindo Classification. Patient was discharged in
      day 8. In our experience laparoscopic resection in cirrhotic liver should be
      performed in selected patients and in an experienced team. 

PMID- 25561776
TI  - Professor Malcolm Mason: what could we do against cancer?

PMID- 25561777
TI  - Pushing the frontiers of living donor right hepatectomy.
AB  - Living donor right hepatectomy (LDRH) is currently the most common donor surgery
      in adult-to-adult living donor liver transplantation although the morbidity and
      mortality reported in living donors still contradicts the Hippocratic tenet of
      "do no harm". Achieving low complication rates in LDRH remains a matter of major
      concern. Living donor surgery is performed worldwide as an established solution
      to the donor shortage. The aim of this study was to assess the current status of
      LDRH and comment on the future of the procedure; assessment was made from the
      standpoint of optimizing the donor selection criteria and reducing morbidity
      based on both the authors' 8-year institutional experience and a literature
      review. New possibilities have been explored regarding selection criteria. The
      safety of living donors with unfavorable conditions, such as low remnant liver
      volume, fatty change, or old age, should also be considered. Abdominal incisions
      have become shorter, even without laparoscopic assistance; upper midline
      laparotomy is the primary incision used in more than 400 consecutive LDRHs in the
      authors' institution. Various surgical techniques based on preoperative imaging
      technology of vascular and biliary anomalies have decreased the anatomical
      barriers in LDRH. Operative time has been reduced, with low blood loss.
      Laparoscopic or robotic LDRH has been tried in only a few selected donors. The
      LDRH-specific, long-term outcomes remain to be addressed. The follow-up duration
      of these studies should be long enough to address possible late complications.
      Donor safety, which is the highest priority, is ensured by three factors:
      preoperative selection, intraoperative surgical technique, and postoperative
      management. These three focus areas should be continuously refined, with the
      ultimate goal of zero morbidity. 

PMID- 25561779
TI  - Fluid resuscitation in acute pancreatitis.
AB  - Acute pancreatitis remains a clinical challenge, despite an exponential increase
      in our knowledge of its complex pathophysiological changes. Early fluid therapy
      is the cornerstone of treatment and is universally recommended; however, there is
      a lack of consensus regarding the type, rate, amount and end points of fluid
      replacement. Further confusion is added with the newer studies reporting better
      results with controlled fluid therapy. This review focuses on the pathophysiology
      of fluid depletion in acute pancreatitis, as well as the rationale for fluid
      replacement, the type, optimal amount, rate of infusion and monitoring of such
      patients. The basic goal of fluid epletion should be to prevent or minimize the
      systemic response to inflammatory markers. For this review, various studies and
      reviews were critically evaluated, along with authors' recommendations, for
      predicted severe or severe pancreatitis based on the available evidence. 

PMID- 25561781
TI  - Dismicrobism in inflammatory bowel disease and colorectal cancer: changes in
      response of colocytes.
AB  - Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15%
      developing colorectal cancer (CRC) that is a common disease of high economic
      costs in developed countries. The CRC has been increasing in recent years and its
      mortality rates are very high. Multiple biological and biochemical factors are
      responsible for the onset and progression of this pathology. Moreover, it appears
      absolutely necessary to investigate the environmental factors favoring the onset
      of CRC and the promotion of colonic health. The gut microflora, or microbiota,
      has an extensive diversity both quantitatively and qualitatively. In utero, the
      intestine of the mammalian fetus is sterile. At birth, the intestinal microbiota
      is acquired by ingesting maternal anal or vaginal organisms, ultimately
      developing into a stable community, with marked variations in microbial
      composition between individuals. The development of IBD is often associated with
      qualitative and quantitative disorders of the intestinal microbial flora
      (dysbiosis). The healthy human gut harbours about 10 different bacterial species
      distributed in colony forming units which colonize the gastrointestinal tract.
      The intestinal microbiota plays a fundamental role in health and in the
      progression of diseases such as IBD and CRC. In healthy subjects, the main
      control of intestinal bacterial colonization occurs through gastric acidity but
      other factors such as endoluminal temperature, competition between different
      bacterial strains, peristalsis and drugs can influence the intestinal
      microenvironment. The microbiota exerts diverse physiological functions to
      include: growth inhibition of pathogenic microorganisms, synthesis of compounds
      useful for the trophism of colonic mucosa, regulation of intestinal lymphoid
      tissue and synthesis of amino acids. Furthermore, mucus seems to play an
      important role in protecting the intestinal mucosa and maintaining its integrity.
      Changes in the microbiota composition are mainly influenced by diet and age, as
      well as genetic factors. Increasing evidence indicates that dysbiosis favors the
      production of genotoxins and metabolites associated with carcinogenesis and
      induces dysregulation of the immune response which promotes and sustains
      inflammation in IBD leading to carcinogenesis. A disequilibrium in gut microflora
      composition leads to the specific activation of gut associated lymphoid tissue.
      The associated chronic inflammatory process associated increases the risk of
      developing CRC. Ulcerative colitis and Crohn's disease are the two major IBDs
      characterized by an early onset and extraintestinal manifestations, such as
      rheumatoid arthritis. The pathogenesis of both diseases is complex and not yet
      fully known. However, it is widely accepted that an inappropriate immune response
      to microbial flora can play a pivotal role in IBD pathogenesis. 

PMID- 25561778
TI  - Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis
      of nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat
      accumulates in the liver of a patient with no history of alcohol abuse or other
      causes for secondary hepatic steatosis. The pathogenesis of NAFLD and
      nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The "two-hit"
      hypothesis is probably a too simplified model to elaborate complex pathogenetic
      events occurring in patients with NASH. It should be better regarded as a
      multiple step process, with accumulation of liver fat being the first step,
      followed by the development of necroinflammation and fibrosis. Adipose tissue,
      which has emerged as an endocrine organ with a key role in energy homeostasis, is
      responsive to both central and peripheral metabolic signals and is itself capable
      of secreting a number of proteins. These adipocyte-specific or enriched proteins,
      termed adipokines, have been shown to have a variety of local, peripheral, and
      central effects. In the current review, we explore the role of adipocytokines and
      proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on
      adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and
      retinol-binding protein 4 among adipokines, and tumor necrosis factor-alpha,
      interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We
      update their role in NAFLD, as elucidated in experimental models and clinical
      practice. 

PMID- 25561780
TI  - New trends in colorectal surgery: single port and natural orifice techniques.
AB  - Single-incision laparoscopic surgery (SILS) and natural orifice transluminal
      endoscopic surgery (NOTES) have rapidly gained pace worldwide, potentially
      replacing conventional laparoscopic surgery (CLS) as the preferred colorectal
      surgery technique. Currently available data mainly consist of retrospective
      series analyzed in four meta-analyses. Despite conflicting results and lack of an
      objective comparison, SILS appears to offer cosmetic advantages over CLS.
      However, due to conflicting results and marked heterogeneity, present data fail
      to show significant differences in terms of operative time, postoperative
      morbidity profiles, port-site complications rates, oncological appropriateness,
      duration of hospitalization or cost when comparing SILS with conventional
      laparoscopy for colorectal procedures. The application of "pure" NOTES in humans
      remains limited to case reports because of unresolved issues concerning the ideal
      access site, distant organ reach, spatial orientation and viscera closure.
      Alternatively, minilaparoscopy-assisted natural orifice surgery techniques are
      being developed. The transanal "down-to-up" total mesorectum excision has been
      derived for transanal endoscopic microsurgery (TEM) and represents the most
      encouraging NOTES-derived technique. Preliminary experiences demonstrate good
      oncological and functional short-term outcomes. Large-scale randomized controlled
      trials are now mandatory to confirm the long-term SILS results and validate
      transanal TEM for the application of NOTES in humans. 

PMID- 25561782
TI  - Non invasive tools for the diagnosis of liver cirrhosis.
AB  - Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of
      different etiologies is a diffuse process characterized by fibrosis and the
      conversion of normal liver architecture into structurally abnormal nodules
      surrounded by annular fibrosis. This chronic progressive clinical condition,
      leads to liver cell failure and portal hypertension, which can favour the onset
      of hepatocellular carcinoma. Defining the phase of the natural history is crucial
      for therapeutic choice and prognosis. Liver biopsy is currently considered the
      best available standard of reference but it has some limits, so alternative tools
      have been developed to substitute liver biopsy when assessing liver fibrosis.
      Serum markers offer a cost-effective alternative to liver biopsy being less
      invasive and theoretically without complications. They can be classified into
      direct and indirect markers which may be used alone or in combination to produce
      composite scores. Diagnostic imaging includes a number of instruments and
      techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US
      Doppler, contrast enhanced US and Elastography. US could be used for the
      diagnosis of advanced LC while is not able to evaluate progression of fibrosis,
      in this case Elastography is more reliable. This review aims to revise the most
      recent data from the literature about non invasive methods useful in defining
      liver fibrosis. 

PMID- 25561784
TI  - Effect of laparoscopic abdominal surgery on splanchnic circulation: historical
      developments.
AB  - With the developments in medical technology and increased surgical experience,
      advanced laparoscopic surgical procedures are performed successfully.
      Laparoscopic abdominal surgery is one of the best examples of advanced
      laparoscopic surgery (LS). Today, laparoscopic abdominal surgery in general
      surgery clinics is the basis of all abdominal surgical interventions.
      Laparoscopic abdominal surgery is associated with systemic and splanchnic
      hemodynamic alterations. Inadequate splanchnic perfusion in critically ill
      patients is associated with increased morbidity and mortality. The underlying
      pathophysiological mechanisms are still not well understood. With experience and
      with an increase in the number and diversity of the resulting data, the
      pathophysiology of laparoscopic abdominal surgery is now better understood. The
      normal physiology and pathophysiology of local and systemic effects of
      laparoscopic abdominal surgery is extremely important for safe and effective LS.
      Future research projects should focus on the interplay between the physiological
      regulatory mechanisms in the splanchnic circulation (SC), organs, and diseases.
      In this review, we discuss the effects of laparoscopic abdominal surgery on the
      SC. 

PMID- 25561783
TI  - Colorectal carcinogenesis--update and perspectives.
AB  - Colorectal cancer (CRC) is a very common malignancy in the Western World and
      despite advances in surgery, chemotherapy and screening, it is still the second
      leading cause of cancer deaths in this part of the world. Numerous factors are
      found important in the development of CRC including colonocyte metabolism, high
      risk luminal environment, inflammation, as well as lifestyle factors such as
      diet, tobacco, and alcohol consumption. In recent years focus has turned towards
      the genetics and molecular biology of CRC and several interesting and promising
      correlations and pathways have been discovered. The major genetic pathways of CRC
      are the Chromosome Instability Pathway representing the pathway of sporadic CRC
      through the K-ras, APC, and P53 mutations, and the Microsatellite Instability
      Pathway representing the pathway of hereditary non-polyposis colon cancer through
      mutations in mismatch repair genes. To identify early cancers, screening programs
      have been initiated, and the leading strategy has been the use of faecal occult
      blood testing followed by colonoscopy in positive cases. Regarding the treatment
      of colorectal cancer, significant advances have been made in the recent decade.
      The molecular targets of CRC include at least two important cell surface
      receptors: the epidermal growth factor receptor and the vascular endothelial
      growth factor receptor. The genetic and molecular knowledge of CRC has widen the
      scientific and clinical perspectives of diagnosing and treatment. However,
      despite significant advances in the understanding and treatment of CRC, results
      from targeted therapy are still not convincing. Future studies will determine the
      role for this new treatment modality.

PMID- 25561786
TI  - Caspase-12 mediates carbon tetrachloride-induced hepatocyte apoptosis in mice.
AB  - AIM: To investigate the role of caspase-12 and its downstream targets in carbon
      tetrachloride (CCl4)-induced hepatocyte apoptosis. METHODS: The role of caspase
      12 was determined by using caspase-12 knock-out ((-/-)) mice. CCl4 (300 MUL/kg
      body weight) or vehicle (corn oil) was administered to caspase-12(+/+) or caspase
      12(-/-) mice as a single intraperitoneal injection. The animals were sacrificed
      24 h after the CCl4 treatment. Blood was collected to evaluate liver function by
      the measurement of the activity of alanine aminotransferase. Liver samples were
      used for the measurements of reactive oxygen species using plasma malondialdehyde
      as biomarker, hepatocyte apoptosis was evaluated via terminal transferase
      mediated dUTP nick-end labeling and controlled by morphologic study, and
      cytochrome C release and caspase activations were measured by Western blotting.
      RESULTS: Administration of a low dose of CCl4 resulted in hepatocyte apoptosis
      and acute liver injury in wild-type mice. CCl4 also induced the generation of
      reactive oxygen species and induction of endoplasmic reticulum stress in the
      liver followed by activations of caspase-12, -9 and -3 as well as release of
      small amounts of cytochrome C. However, in the CCl4-treated caspase-12(-/-) mice,
      activation of caspase-9 and -3 were significantly attenuated (P < 0.05); no
      effect was seen in cytochrome C release. CCl4-induced apoptosis and liver damage
      was markedly reduced in caspase-12(-/-) mice compared to caspase-12(+/+) mice (P
      < 0.05). The active form of caspase-8 was not detected in either caspase-12(+/+)
      or caspase-12(-/-) mice. There was no significant different in the formation of
      reactive oxygen species in the livers of caspase-12(+/+) and caspase-12(-/-) mice
      treated with CCl4. CONCLUSION: Caspase-12 plays a pivotal role in CCl4-induced
      hepatic apoptosis through the activation of the downstream effector caspase-3
      directly and/or indirectly via caspase-9 activation.

PMID- 25561785
TI  - Role of interleukin-22 in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disease thought to be
      mediated by the microbiota of the intestinal lumen and inappropriate immune
      responses. Aberrant immune responses can cause secretion of harmful cytokines
      that destroy the epithelium of the gastrointestinal tract, leading to further
      inflammation. Interleukin (IL)-22 is a member of the IL-10 family of cytokines
      that was recently discovered to be mainly produced by both adaptive and innate
      immune cells. Several cytokines and many of the transcriptional factors and T
      regulatory cells are known to regulate IL-22 expression through activation of
      signal transducer and activator of transcription 3 signaling cascades. This
      cytokine induces antimicrobial molecules and proliferative and antiapoptotic
      pathways, which help prevent tissue damage and aid in its repair. All of these
      processes play a beneficial role in IBD by enhancing intestinal barrier integrity
      and epithelial innate immunity. In this review, we discuss recent progress in the
      involvement of IL-22 in the pathogenesis of IBD, as well as its therapeutic
      potential. 

PMID- 25561787
TI  - Biodegradable stent or balloon dilatation for benign oesophageal stricture: pilot
      randomised controlled trial.
AB  - AIM: To undertake a randomised pilot study comparing biodegradable stents and
      endoscopic dilatation in patients with strictures. METHODS: This British multi
      site study recruited seventeen symptomatic adult patients with refractory
      strictures. Patients were randomised using a multicentre, blinded assessor
      design, comparing a biodegradable stent (BS) with endoscopic dilatation (ED). The
      primary endpoint was the average dysphagia score during the first 6 mo. Secondary
      endpoints included repeat endoscopic procedures, quality of life, and adverse
      events. Secondary analysis included follow-up to 12 mo. Sensitivity analyses
      explored alternative estimation methods for dysphagia and multiple imputation of
      missing values. Nonparametric tests were used. RESULTS: Although both groups
      improved, the average dysphagia scores for patients receiving stents were higher
      after 6 mo: BS-ED 1.17 (95%CI: 0.63-1.78) P = 0.029. The finding was robust under
      different estimation methods. Use of additional endoscopic procedures and quality
      of life (QALY) estimates were similar for BS and ED patients at 6 and 12 mo.
      Concomitant use of gastrointestinal prescribed medication was greater in the
      stent group (BS 5.1, ED 2.0 prescriptions; P < 0.001), as were related adverse
      events (BS 1.4, ED 0.0 events; P = 0.024). Groups were comparable at baseline and
      findings were statistically significant but numbers were small due to under
      recruitment. The oesophageal tract has somatic sensitivity and the process of the
      stent dissolving, possibly unevenly, might promote discomfort or reflux.
      CONCLUSION: Stenting was associated with greater dysphagia, co-medication and
      adverse events. Rigorously conducted and adequately powered trials are needed
      before widespread adoption of this technology.

PMID- 25561788
TI  - 2,4,6-trinitrobenzene sulfonic acid-induced chronic colitis with fibrosis and
      modulation of TGF-beta1 signaling.
AB  - AIM: To investigate whether targeting proteasome might reverse intestinal
      fibrosis in rats. METHODS: Chronic colitis was induced in rats by repeated
      administration of increasing dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS,
      15, 30, 45, 60, 60, 60 mg) by rectal injection for 6 wk (from day 0 to day 35),
      while control rats received the vehicle. TNBS + bortezomib (BTZ) rats received
      intraperitoneal injections of BTZ twice weekly (from day 37 to day 44) at a dose
      of 25 mg/kg, whereas the control and TNBS groups received the same amount of the
      vehicle. Histologic scoring of inflammation and fibrosis was performed. Colonic
      production of transforming growth factor (TGF)-beta was measured by ELISA. Colon
      fibrosis-related proteins such as phospho-p38, phospho-SMAD2/3, Akt and
      peroxisome proliferator activated receptor gamma (PPARgamma) were studied by
      western blot. Expression of the tight junction proteins, occludin and claudin-1,
      were assessed by Western blot. Colon proteasome activities (chymotrypsin-like and
      trypsin-like activities) were assessed. RESULTS: TNBS-treated rats had a higher
      colon weight/length ratio compared to control rats (P < 0.01). Furthermore,
      fibrosis and inflammation scores were higher in TNBS-treated rats compared to
      control rats (P < 0.01 for both). Colonic production of TGF-beta production
      tended to be higher in TNBS-treated rats (P < 0.06). Fibrosis-related proteins
      such as phospho-p38, phospho-SMAD2/3, and PPARgamma were significantly higher in
      TNBS-treated rats compared to control rats (all P < 0.05). TNBS rats had a higher
      expression of Akt compared to control rats (P < 0.01). Tight junction proteins
      were modified by repeated TNBS challenge: colon occludin expression rose
      significantly (P < 0.01), whereas claudin-1 expression fell (P < 0.01).
      Bortezomib inhibition significantly decreased chymotrypsin-like activity (P <
      0.05), but had no significant effect on trypsin-like activity (P > 0.05). In
      contrast, bortezomib had no effect on other studied parameters such as fibrosis
      score, TGF-beta signaling, or tight junction expression (P > 0.05 for all).
      CONCLUSION: Rats with TNBS-induced chronic colitis exhibited colon fibrosis
      associated with higher TGF-beta signaling. Proteasome inhibition by bortezomib
      had no effect on fibrosis in our experimental conditions.

PMID- 25561789
TI  - Motility patterns of ex vivo intestine segments depend on perfusion mode.
AB  - AIM: To evaluate and characterize motility patterns from small intestinal gut
      segments depending on different perfusion media and pressures. METHODS:
      Experiments were carried out in a custom designed perfusion chamber system to
      validate and standardise the perfusion technique used. The perfusion chamber was
      built with a transparent front wall allowing for optical motility recordings and
      a custom made fastener to hold the intestinal segments. Experiments with
      different perfusion and storage media combined with different luminal pressures
      were carried out to evaluate the effects on rat small intestine motility.
      Software tools which enable the visualization and characterization of intestinal
      motility in response to different stimuli were used to evaluate the videotaped
      experiments. The data collected was presented in so called heatmaps thus
      providing a concise overview of form and strength of contractility patterns.
      Furthermore, the effect of different storage media on tissue quality was
      evaluated. Haematoxylin-Eosin stainings were used to compare tissue quality
      depending on storage and perfusion mode. RESULTS: Intestinal motility is
      characterized by different repetitive motility patterns, depending on the actual
      situation of the gut. Different motility patterns could be recorded and
      characterized depending on the perfusion pressure and media used. We were able to
      describe at least three different repetitive patterns of intestinal motility in
      vitro. Patterns with an oral, anal and oro-anal propagation direction could be
      recorded. Each type of pattern finalized its movement with or without a
      subsequent distension of the wavefront. Motility patterns could clearly be
      distinguished in heatmap diagrams. Furthermore undirected motility could be
      observed. The quantity of the different patterns varies and is highly dependent
      on the perfusion medium used. Tissue preservation varies depending on the
      perfusion medium utilized, therefore media with a simple composition as Tyrode
      solution can only be recommended for short time experiments. The more complex
      media, MEM-HEPES medium and especially AQIX((r)) RS-I tissue preservation reagent
      preserved the tissue much better during perfusion. CONCLUSION: Perfusion media
      have to be carefully chosen considering type and duration of the experiments. If
      excellent tissue quality is required, complex media are favorable. Perfusion
      pressure is also of great importance due to the fact that a minimum amount of
      luminal pressure seems to be necessary to trigger intestinal contractions.

PMID- 25561790
TI  - Intravenous vs intraperitoneal mesenchymal stem cells administration: what is the
      best route for treating experimental colitis?
AB  - AIM: To investigate the therapeutic effects of mesenchymal stem cells (MSCs)
      transplanted intraperitoneally and intravenously in a murine model of colitis.
      METHODS: MSCs were isolated from C57BL/6 mouse adipose tissue. MSC cultures were
      analyzed according to morphology, cellular differentiation potential, and surface
      molecular markers. Experimental acute colitis was induced in C57BL/6 mice by oral
      administration of 2% dextran sulfate sodium (DSS) in drinking water ad libitum
      from days 0 to 7. Colitis mice were treated with 1 * 10(6) MSCs via
      intraperitoneal or intravenous injection on days 2 and 5. The disease activity
      index was determined daily based on the following parameters: weight loss, stool
      consistency and presence of blood in the feces and anus. To compare morphological
      and functional differences in tissue regeneration between different MSC injection
      modalities, mice were euthanized on day 8, and their colons were examined for
      length, weight, and histopathological changes. Inflammatory responses were
      determined by measuring the levels of different serum cytokines using a CBA
      Th1/Th2/Th17 kit. Apoptotic rates were evaluated by terminal deoxynucleotidyl
      transferase-mediated dUDP-biotin nick end labeling assay. RESULTS: Intravenous
      infusion of MSCs was more effective than intraperitoneal treatment (P < 0.001) in
      reducing the clinical and histopathologic severity of colitis, which includes
      weight loss, diarrhea and inflammation. An histological evaluation demonstrated
      decreased colonic inflammation based on reduced crypt loss and reduced
      infiltration of inflammatory cells. This therapeutic effect was most likely
      mediated by the down-regulation of pro-inflammatory cytokines [interleukin (IL)-6
      and tumor necrosis factor (TNF)]; and by the up-regulation of anti-inflammatory
      cytokines (IL-10 and IL-4). Intravenous transplantation also induced high levels
      of IFN that lead to activation of the immunosuppressive activity of the MSCs,
      which did not occur with intraperitoneal transplantation (P = 0.006). An increase
      in apoptotic T cells was observed after intravenous, but not intraperitoneal, MSC
      infusion, suggesting that MSCs can induce apoptosis in resistant T cells in
      colonic inflammation (P = 0.027). CONCLUSION: Our results demonstrate that
      intravenous treatment is a superior method for reducing colon inflammation
      compared with intraperitoneal therapy.

PMID- 25561791
TI  - Circulating tumor and cancer stem cells in hepatitis C virus-associated liver
      disease.
AB  - AIM: To assess the role of circulating tumor cells (CTCs) and cancer stem cells
      (CSCs) in hepatitis C virus (HCV)-associated liver disease. METHODS: Blood and/or
      tissue samples were obtained from HCV (genotype 4)-associated hepatocellular
      carcinoma patients (HCC; n = 120), chronic hepatitis C patients (CH; n = 30) and
      33 normal control subjects (n = 33). Serum levels of alpha-fetoprotein (AFP),
      alkaline phosphatase, and alanine and aspartate aminotransferases were measured.
      Cytokeratin 19 (CK19) monoclonal antibody was used to enumerate CTCs, and CD133
      and CD90 were used to enumerate CSCs by flow cytometry. The expression levels of
      the CSCs markers (CD133 and CD90) as well as telomerase, melanoma antigen
      encoding gene 1 (MAGE1) and MAGE3 were assessed by RT-PCR and quantitative real
      time polymerase chain reactions. The number of CTCs and/or the expression levels
      of CK19, CD133, telomerase, MAGE1 and MAGE3 were correlated to the standard
      clinicopathologic prognostic factors and disease progression. RESULTS: Levels of
      AFP, alkaline phosphatase and aspartate aminotransferase were significantly
      different among the HCC, CH and control groups (P < 0.001), whereas alanine
      aminotransferase differed significantly between patient (HCC and CH) and control
      groups (P < 0.001). At the specified cutoff values determine by flow cytometry,
      CK19 (49.8), CD90 (400) and CD133 (73) were significantly higher in the blood of
      HCC patients compared to those in the CH and control groups (P < 0.001). On the
      other hand, CD133 at a 69.5 cutoff was significantly higher in the CH compared to
      the control group (P <= 0.001). Telomerase, MAGE1 and MAGE3 RNA were expressed in
      55.71%, 60.00% and 62.86% of the HCC patients, respectively, but were not
      detected in patients in the CH or control groups, which were statistically
      significant (Ps < 0.001). The expression levels of telomerase, CD90, MAGE3, CD133
      and CK19 were all significantly associated with high tumor grade and advanced
      stage in HCC patients (all Ps < 0.05). CONCLUSION: CTC counts and AFP, CK19,
      telomerase, and MAGE1/MAGE3 expression predict disease progression in patients
      with HCV, whereas telomerase, MAGE3, CD90, CD133 and CK19 are prognostic markers
      in HCC.

PMID- 25561792
TI  - Delayed ethanol elimination and enhanced susceptibility to ethanol-induced
      hepatosteatosis after liver resection.
AB  - AIM: To investigate ethanol-induced hepatic steatosis after liver resection and
      the mechanisms behind it. METHODS: First, the preliminary examination was
      performed on 6 sham-operated (Sham) and 30 partial hepatectomy (PH) male Wistar
      rats (8-wk-old) to evaluate the recovery of the liver weight and liver function
      after liver resection. PH rats were sacrificed at the indicated time points (4,
      8, and 12 h; 1, 3, and 7 d) after PH. Second, the time point for the beginning of
      the chronic ethanol exposure (1 wk after sham- or PH-operation) was determined
      based on the results of the preliminary examination. Finally, pair-feeding was
      performed with a controlled diet or with a 5-g/dL ethanol liquid diet for 28 d in
      another 35 age-matched male Wistar rats with a one-week recovery after undergoing
      a sham- (n = 15) or PH-operation (n = 20) to evaluate the ethanol-induced liver
      injury after liver resection. Hepatic steatosis, liver function, fatty acid
      synthase (Fas) gene expression level, the expression of lipid metabolism
      associated enzyme regulator genes [sterol regulatory element binding protein
      (Srebp)-1 and peroxisome proliferator-activated receptor (Ppar)-alpha], the
      mediators that alter lipid metabolism [plasminogen activator (Pai)-1 gene
      expression level and tumor necrosis factor (Tnf)-alpha production], and hepatic
      class-1 alcohol dehydrogenase (Adh1)-associated ethanol elimination were
      investigated in the 4 groups based on histological, immunohistochemical,
      biochemical, Western blotting, reverse transcriptase chain reaction, and blood
      ethanol concentration analyses. The relevant gene expression levels, liver
      weight, and liver function were assessed before and 1 wk after surgery to
      determine the subject's recovery from the liver resection using the rats that had
      been subjected to the preliminary examination. RESULTS: In the PH rats, ethanol
      induced marked hepatic steatosis with impaired liver functioning, as evidenced by
      the accumulation of fatty droplets within the hepatocytes, the higher increases
      in their hepatic triglyceride and blood alanine aminotransferase and blood
      aspartate aminotransferase levels after the 28-d pair-feeding period. The Sham
      ethanol rats, not the PH-ethanol rats, demonstrated the up-regulation of Srebp-1
      and the down-regulation of Ppar-alpha mRNA expression levels after the 28-d pair
      feeding period. The 28-d ethanol administration induced the up-regulation of Pai
      1 gene expression level and an overproduction of TNF-alpha in the Sham and the PH
      rats; however, the effect was more significant in the PH rats. The PH-ethanol
      rats (n = 4) showed higher residual blood ethanol concentrations than did the
      Sham-ethanol rats (n = 6) after a 5-h fast (0.66 +/- 0.4 mg/mL vs 0.2 +/- 0.1
      mg/mL, P < 0.05); these effects manifested without up-regulation of Adh1 gene
      expression, which was present in the Sham-ethanol group after the 28-d pair
      feeding period. One week after the liver resection, the liver weight, function,
      the gene expression levels of Fas, Srebp-1, Ppar-alpha, Pai-1 and Tnf-alpha
      recovered; however, the Adh1 gene expression did not recover in rats. CONCLUSION:
      Desensitization to post-hepatectomy ethanol treatment and slow recovery from PH
      in Adh1 gene expression enhanced the susceptibility to ethanol-induced hepatic
      steatosis after PH in rats.

PMID- 25561793
TI  - PBX3 promotes migration and invasion of colorectal cancer cells via activation of
      MAPK/ERK signaling pathway.
AB  - AIM: To investigate the role of pre-B-cell leukemia homeobox (PBX)3 in migration
      and invasion of colorectal cancer (CRC) cells. METHODS: We detected PBX3
      expression in five cell lines and surgical specimens from 111 patients with CRC
      using real-time reverse transcription-polymerase chain reaction. We forced
      expression of PBX3 in low metastatic HT-29 and SW480 cells and knocked down
      expression of PBX3 in highly metastatic LOVO and HCT-8 cells. Wound healing and
      Boyden chamber assays were used to detect cell migration and invasion after
      altered expression of PBX3. Western blot was performed to detect the change of
      signaling molecule ERK1/2 following PBX3 overexpression. RESULTS: High level of
      PBX3 expression was correlated with the invasive potential of CRC cells, and
      significantly associated with lymph node invasion (P = 0.02), distant metastasis
      (P = 0.04), advanced TNM stage (P = 0.03) and poor overall survival of patients
      (P < 0.05). Ectopic expression of PBX3 in low metastatic cells was shown to
      promote migration and invasion, while inhibited PBX3 expression in highly
      metastatic cells suppressed migration and invasion. Furthermore, upregulation of
      phosphorylated extracellular signal-regulated kinase (ERK)1/2 was found to be one
      of the targeted molecules responsible for PBX3-induced CRC cell migration and
      invasion. CONCLUSION: PBX3 induces invasion and metastasis of CRC cells partially
      through activation of the MAPK/ERK signaling pathway.

PMID- 25561794
TI  - Acupuncture at heterotopic acupoints enhances jejunal motility in constipated and
      diarrheic rats.
AB  - AIM: To investigate the effect and mechanism of acupuncture at heterotopic
      acupoints on jejunal motility, particularly in pathological conditions. METHODS:
      Jejunal motility was assessed using a manometric balloon placed in the jejunum
      approximately 18-20 cm downstream from the pylorus and filled with approximately
      0.1 mL warm water in anesthetized normal rats or rats with diarrhea or
      constipation. The heterotopic acupoints including LI11 (Quchi), ST37 (Shangjuxu),
      BL25 (Dachangshu), and the homotopic acupoint ST25 (Tianshu), and were stimulated
      for 60 s by rotating acupuncture needles right and left at a frequency of 2 Hz.
      To determine the type of afferent fibers mediating the regulation of jejunal
      motility by manual acupuncture, the ipsilateral sciatic A or C fibers of ST37
      were inactivated by local application of the A-fiber selective demyelination
      agent cobra venom or the C fiber blocker capsaicin. Methoctramine, a selective M2
      receptor antagonist, was injected intravenously to identify a specific role for
      M2 receptors in mediating the effect of acupuncture on jejunal motility. RESULTS:
      Acupuncture at heterotopic acupoints, such as LI11 and ST37, increased jejunal
      motility not only in normal rats, but also in rats with constipation or diarrhea.
      In normal rats, manual acupuncture at LI11 or ST37 enhanced jejunal pressure from
      7.34 +/- 0.19 cmH2O to 7.93 +/- 0.20 cmH2O, an increase of 9.05% +/- 0.82% (P <
      0.05), and from 6.95 +/- 0.14 cmH2O to 8.97 +/- 0.22 cmH2O, a significant
      increase of 27.44% +/- 1.96% (P < 0.01), respectively. In constipated rats,
      manual acupuncture at LI11 or ST37 increased intrajejunal pressure from 8.17 +/-
      0.31 cmH2O to 9.86 +/- 0.36 cmH2O, an increase of 20.69% +/- 2.10% (P < 0.05),
      and from 8.82 +/- 0.28 cmH2O to 10.83 +/- 0.28 cmH2O, an increase of 22.81% +/-
      1.46% (P < 0.05), respectively. In rats with diarrhea, MA at LI11 or ST37
      increased intrajejunal pressure from 11.95 +/- 0.35 cmH2O to 13.96 +/- 0.39
      cmH2O, an increase of 16.82% +/- 2.35% (P < 0.05), and tended to increase
      intrajejunal pressure (from 12.42 +/- 0.38 cmH2O to 13.05 +/- 0.38 cmH2O, an
      increase of 5.07% +/- 1.08%, P > 0.05), respectively. In contrast, acupuncture
      ST25, a homotopic acupoint, decreased not only intrajejunal pressure, but also
      significantly decreased frequency in normal rats and rats with constipation or
      diarrhea. Following demyelination of Adelta fibers, acupuncture at ST37 again
      augmented intrajejunal pressure to 121.48% +/- 3.06% of baseline. Following
      capsaicin application for 24 h, acupuncture at ipsilateral ST37 increased
      intrajejunal pressure significantly to 106.63% +/- 1.26% of basal levels when
      compared to measurements prior to capsaicin treatment (P < 0.05). Acupuncture at
      LI11, ST37, or BL25 significantly rescued methoctramine-mediated inhibition of
      jejunal motility amplitude from 42.83% +/- 1.65% to 53.43% +/- 1.95% of baseline
      (P < 0.05), from 45.15% +/- 2.22% to 70.51% +/- 2.34% of baseline (P < 0.01), and
      from 38.03% +/- 2.34% to 70.12% +/- 2.22% of baseline (P < 0.01), respectively.
      CONCLUSION: Acupuncture at heterotopic acupoints increases the amplitude of
      jejunal motility in rats. C fibers and M2 receptors predominantly and partially
      mediate the regulation of jejunal motility by acupuncture, respectively.

PMID- 25561795
TI  - Tricistronic hepatitis C virus subgenomic replicon expressing double transgenes.
AB  - AIM: To construct a tricistronic hepatitis C virus (HCV) replicon with double
      internal ribosome entry sites (IRESes) of only 22 nucleotides for each,
      substituting the encephalomyocarditis virus (EMCV) IRESes, which are most often
      used as the translation initiation element to form HCV replicons. METHODS: The
      alternative 22-nucleotide IRES, RNA-binding motif protein 3 IRES (Rbm3 IRES), was
      used to form a tricistronic HCV replicon, to facilitate constructing HCV
      harboring stable cell lines and successive antiviral screening using a luciferase
      marker. Briefly, two sequential Rbm3 IRESes were inserted into bicistronic pUC19
      HCV plasmid, consequently forming a tricistronic HCV replicon (pHCV-rep-NeoR
      hRluc), initiating the translation of humanized Renilla luciferase and HCV non
      structural gene, along with HCV authentic IRES initiating the translation of
      neomycin resistance gene. The sH7 cell lines, in which the novel replicon RNA
      stably replicated, were constructed by neomycin and luciferase activity
      screening. The intracellular HCV replicon RNA, expression of inserted foreign
      genes and HCV non-structural gene, as well as response to anti-HCV agents, were
      measured in sH7 cells and cells transiently transfected with tricistronic
      replicon RNA. RESULTS: The intracellular HCV replicon RNA and expression of
      inserted foreign genes and HCV non-structural gene in sH7 cells and cells
      transiently transfected with tricistronic replicon RNA were comparable to those
      in cells stably or transiently transfected with traditional bicistronic HCV
      replicons. The average relative light unit in pHCV-rep-NeoR-hRluc group was
      approximately 2-fold of those in the pUC19-HCV-hRLuc and Tri-JFH1 groups (1.049 *
      10(8) +/- 2.747 * 10(7) vs 5.368 * 10(7) +/- 1.016 * 10(7), P < 0.05; 1.049 *
      10(8) +/- 2.747 * 10(7) vs 5.243 * 10(7) +/- 1.194 * 10(7), P < 0.05), suggesting
      that the translation initiation efficiency of the first Rbm3 IRES in the two
      sequential IRESes was stronger than the HCV authentic IRES and EMCV IRES. The
      fold changes of 72 h/4 h relative light units in the pHCV-rep-NeoR-hRluc and
      pUC19-HCV-hRLuc groups were similar (159.619 +/- 9.083 vs 163.536 +/- 24.031, P =
      0.7707), and were both higher than the fold change in the Tri-JFH1 group
      159.619+/- 9.083 vs 140.811 +/- 9.882, P < 0.05; 163.536 +/- 24.031 vs 140.811 +/
      9.882, P < 0.05), suggesting that the replication potency of the Rbm3 IRES
      tricistronic replicon matched the replication of bicistronic replicon and
      exceeded the potency of EMCV IRES replicon. Replication of tricistronic replicons
      was suppressed by ribavirin, simvastatin, atorvastatin, telaprevir and
      boceprevir. Interferon-alpha 2b could not block replication of the novel replicon
      RNA in sH7 cells. After interferon stimulation, MxA mRNA and protein levels were
      lower in sH7 than in parental cells. CONCLUSION: Tricistronic HCV replicon with
      double Rbm3 IRESes could be applied to evaluate the replication inhibition
      efficacy of anti-HCV agents.

PMID- 25561796
TI  - Radiobiological characteristics of cancer stem cells from esophageal cancer cell
      lines.
AB  - AIM: To study the cancer stem cell population in esophageal cancer cell lines
      KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells
      display cancer stem cells and radiation resistance characteristics. METHODS: A
      serum-free medium (SFM) suspension was used to culture esophageal cancer stem
      cell lines and enrich the esophageal stem-like spheres. A reverse transcription
      polymerase chain reaction assay was used to detect stem cell gene expression in
      the spheroid cells. Radiosensitivity of stem-like spheres and parental cells were
      evaluated by clonogenic assays. Furthermore, different cells after different
      doses of irradiation were tested to evaluate the change in sphere formation, cell
      cycle and CD44(+)CD271(+) expression of tumor stem-like spheroid cells using flow
      cytometry before and after irradiation. RESULTS: The cells were observed to
      generate an increased number of spheres in SFM with increasing cell passage.
      Radiation increased the rate of generation of stem-like spheres in both types of
      cells. The average survival fraction (SF2) of the cultured KYSE-150 compared with
      TE-1 stem-like spheres after 2 Gy of radiation was 0.81 +/- 0.03 vs 0.87 +/- 0.01
      (P < 0.05), while the average SF2 of KYSE-150 compared with TE-1 parental cells
      was 0.69 +/- 0.04 vs 0.80 +/- 0.03, P < 0.05. In the esophageal parental cells,
      irradiation dose-dependently induced G2 arrest. Stem-like esophageal spheres were
      resistant to irradiation-induced G2 arrest without significant changes in the
      percentage population of irradiated stem-like cells. Under irradiation at 0, 4,
      and 8 Gy, the CD44(+)CD271(+) cell percentage for KYSE150 parental cells was
      1.08% +/- 0.03% vs 1.29% +/- 0.07% vs 1.11% +/- 0.09%, respectively; the
      CD44(+)CD271(+) cell percentage for TE1 parental cells was 1.16% +/- 0.11% vs
      0.97% +/- 0.08% vs 1.45% +/- 0.35%, respectively. The differences were not
      statistically significant. Under irradiation at 0, 4, and 8 Gy, the
      CD44(+)CD271(+) cell percentage for KYSE-150 stem-like spheres was 35.83% +/-
      1.23% vs 44.9% +/- 1.67% vs 57.77% +/- 1.88%, respectively; the CD44(+)CD271(+)
      cell percentage for TE1 stem-like spheres was 16.07% +/- 0.91% vs 22.67% +/-
      1.12%, 16.07% +/- 0.91% vs 33.27% +/- 1.07%, respectively. The 4 and 8 Gy
      irradiated KYSE-150 and TE-1 stem-like spheres were compared with the 0 Gy
      irradiated group, and the differences were statistically significant (P < 0.05).
      CONCLUSION: The KYSE-150 and TE-1 stem-like spheres are more radioresistant than
      their parental cells which may suggest that cancer stem cells are related to
      radioresistance.

PMID- 25561797
TI  - Twist1 correlates with poor differentiation and progression in gastric
      adenocarcinoma via elevation of FGFR2 expression.
AB  - AIM: To explore the correlation between Twist-related protein (Twist)1,
      fibroblast growth factor receptor (FGFR)2 and gastric adenocarcinoma
      differentiation and progression. METHODS: We evaluated Twist1 and FGFR2 in 52
      gastric adenocarcinoma samples by immunohistochemistry and quantitative real time
      polymerase chain reaction, and analyzed the correlation between Twist1, FGFR2 and
      cancer differentiation. We also detected Twist1 and FGFR2 expression in gastric
      adenocarcinoma cell lines, and evaluated Twist1 influence on FGFR2 expression. In
      addition, we studied the role of FGFR2 in Twist1-promoted cancer progression,
      including proliferation, invasion and epithelial-mesenchymal transition (EMT).
      RESULTS: Twist1 and FGFR2 were detected in almost all the gastric adenocarcinoma
      samples. Twist1 (P = 0.0213) and FGFR2 (P = 0.0310) mRNA levels had a significant
      association with gastric adenocarcinoma differentiation. Moreover, Twist1 and
      FGFR2 expression in poorly differentiated cells (SNU-1 and SNU-16) was notably
      higher than in well-differentiated cells (MKN-7 and MKN-28). In poorly
      differentiated gastric adenocarcinomas, FGFR2 mRNA level was significantly
      positively correlated with Twist1 mRNA level (P = 0.004). Twist1 was proved to
      promote FGFR2 by regulating Twist1 expression by knockdown and overexpression.
      Additionally, Twist1 could induce proliferation, invasion and EMT in gastric
      cancer; of these, FGFR2 was required for invasion and EMT, rather than
      proliferation. CONCLUSION: Twist1 and FGFR2 are highly associated with
      differentiation of gastric adenocarcinoma; Twist1 can facilitate invasion and EMT
      in gastric adenocarcinoma via promotion of FGFR2 expression.

PMID- 25561798
TI  - Bifidobacterium infantis attenuates colitis by regulating T cell subset
      responses.
AB  - AIM: to investigate the effect of Bifidobacterium infantis (B. infantis) on the T
      cell subsets and in attenuating the severity of experimental colitis in mice.
      METHODS: Normal BALB/c mice were fed different doses of B. infantis for 3 wk, and
      T cell subsets and related cytokine profiles in mesenteric lymph nodes (MLNs)
      were detected by flow cytometry and real-time RT-PCR. Colitis was induced by
      administration of trinitrobenzene sulfonic acid (TNBS) in mice. Before colitis
      induction, mice were fed high dose B. infantis for 3 wk. Cytokine profiles in
      MLNs and histological changes of colonic tissue were examined 6 d after colitis
      induction. RESULTS: No significant change in cytokine profiles was observed in
      normal mice fed low dose B. infantis. However, Th1-related cytokines (IL-2, IFN
      gamma, IL-12p40), Th17-related transcription factor and cytokines (RORgammat, IL
      21, IL-23), regulatory T cell (Treg)-related transcription factor and cytokines
      (Foxp3, IL-10) were increased in normal mice fed high dose B. infantis.
      Furthermore, flow cytometry assay showed B. infantis increased the numbers of
      CD4(+)Foxp3(+) Tregs and Th17 cells in MLNs. Colitis was successfully induced by
      TNBS in mice, characterized by colonic inflammation and aberrant Th1 and Th17
      responses. Feeding high dose B. infantis for 3 wk before colitis induction
      decreased the inflammatory cell infiltration and goblet cell depletion and
      restored the intestinal epithelium. In addition, B. infantis feeding reduced Th1
      related cytokines (T-bet, IL-2 and IFN-gamma) and Th17-related cytokines (IL
      12p40, RORgammat, IL-17A, IL-21 and IL-23), and increased Treg-related molecules
      (Foxp3, IL-10 and TGF-beta) in colitis mice. CONCLUSION: B. infantis effectively
      attenuates TNBS-induced colitis by decreasing Th1 and Th17 responses and
      increasing Foxp3(+) Treg response in the colonic mucosa.

PMID- 25561799
TI  - Aloe vera attenuated gastric injury on indomethacin-induced gastropathy in rats.
AB  - AIM: To evaluate the protective effects of Aloe vera on gastric injury in rats
      with indomethacin (IMN)-induced gastropathy. METHODS: Male Sprague-Dawley rats
      were randomly divided into three groups. Group 1 (control, n = 6) was given
      distilled water (DW) orally. Group 2 (IMN, n = 6) was given oral IMN (150 mg/kg)
      dissolved in 5% sodium bicarbonate (NaHCO3 (-)) at time 0 and 4 h. Group 3 (Aloe
      vera-treated, n = 6) was given oral Aloe vera (150 mg/kg) dissolved in DW and IMN
      at time 0 and 4 h. Eight hours later, the stomach was removed to determine
      gastric malondialdehyde (MDA), the number of interleukin (IL)-18 positive stained
      cells (%) by immunohistochemistry, and for histopathological examination. Then,
      the serum was collected to determine tumor necrosis factor (TNF)-alpha and
      cytokine-induced neutrophil chemoattractant (CINC)-1 by sandwich enzyme linked
      immunosorbent assay method. RESULTS: In the IMN group, serum TNF-alpha, CINC-1
      and gastric MDA were significantly increased when compared to the control group
      (27.78 +/- 1.52 pg/mL vs 85.07 +/- 49.11 pg/mL, P = 0.009; 104.55 +/- 45.80 pg/mL
      vs 1054.70 +/- 20.38 pg/mL, and 1.74 +/- 0.21 nmol/mg vs 9.36 +/- 1.07 nmol/mg
      protein, P = 0.000, respectively). The mean level of TNF-alpha, CINC-1 and
      gastric MDA in the Aloe vera-treated group were improved as compared with the IMN
      group (85.07 +/- 49.11 pg/mL vs 35.19 +/- 1.61 pg/mL, P = 0.021; 1054.70 +/-
      20.38 pg/mL vs 813.56 +/- 239.04 pg/mL, P = 0.025; and 9.36 +/- 1.07 nmol/mg vs
      2.67 +/- 0.64 nmol/mg protein, P = 0.000, respectively). The number of IL-18
      positive stained cells (%) in the gastric epithelial cells of the IMN group was
      significantly higher than the control group (5.01% +/- 3.73% vs 30.67% +/- 2.03%,
      P = 0.000, respectively). In contrast, Aloe vera treatment decreased the number
      of IL-18 positive stained cells (%) significantly when compared with the IMN
      group (30.67% +/- 2.03% vs 13.21% +/- 1.10%, P = 0.000, respectively). Most rats
      in the IMN group developed moderate to severe gastric inflammation and erosions.
      The gastric erosions and neutrophil infiltration scores were significantly
      reduced in the Aloe vera-treated group. CONCLUSION: Aloe vera attenuated IMN
      induced gastropathy in rats by the reduction of oxidative stress, inflammation,
      and improvement of gastric histopathology.

PMID- 25561800
TI  - Comparative study of mutations in SNP loci of K-RAS, hMLH1 and hMSH2 genes in
      neoplastic intestinal polyps and colorectal cancer.
AB  - AIM: To clarify the molecular mechanism involved in pathogenesis of colorectal
      cancer as well as clinical significance of genetic analysis of histological
      samples. METHODS: A total of 480 blood and tissue specimens were collected in our
      hospital from January 2011 to October 2012. In the observation group, there were
      120 blood specimens and 120 intestinal tract tissue specimens collected from
      patients with neoplastic intestinal polyps. In the control group I there were 80
      blood specimens and 80 intestinal tract tissue specimens collected from patients
      with colorectal cancer. In the control group II there were 40 blood specimens and
      40 intestinal tract tissue specimens collected from healthy individuals. The gene
      segments were amplified using PCR and DNA gel electrophoresis along with DNA
      sequence analysis were employed for the detection of the following single
      nucleotide polymorphisms (SNPs): K-RAS codons 12 and 13; hMLH1 (human mutS
      homolog 1) gene missense mutation at Va1384Asp; hMSH2 (human mutS homolog 2) gene
      missense mutation at 2783C/A. RESULTS: The mutation rate of the SNP at Va1384Asp
      locus of the hMLH1 gene from blood and tissue specimens in the observation group
      showed no statistical difference from those in the control group I. The mutation
      rates of SNPs in codons 12 and 13 of K-RAS and at 2783C/A locus of the hMSH2 gene
      were significantly lower in the observation group than in the control group I
      (chi(2) = 15.476, 29.670, 10.811, 16.618, 33.538, 7.898, P < 0.05). The mutation
      rate of SNP at Va1384Asp locus of the hMLH1 gene was significantly higher in the
      observation group when compared to the control group II (chi(2) = 10.486, 4.876,
      P < 0.05). The mutation rates of SNPs in codons 12 and 13 of K-RAS and at 2783C/A
      locus of the hMSH2 gene did not show any statistical difference from those in the
      control group II. CONCLUSION: There may be important clinical significance and
      relevance between neoplastic intestinal polyps and colorectal cancer in terms of
      the mechanisms involved in the pathogenesis.

PMID- 25561801
TI  - Zinc finger protein 139 expression in gastric cancer and its clinical
      significance.
AB  - AIM: To investigate the expression of zinc finger protein 139 (ZNF139) in gastric
      cancer (GC), and to analyze its clinical significance. METHODS: A total of 108
      patients who were diagnosed with GC and underwent surgery between January 2005
      and March 2007 were enrolled in this study. Gastric tumor specimens and paired
      tumor-adjacent tissues were collected and paraffin-embedded, and the
      clinicopathologic characteristics and prognosis were recorded. The expression of
      ZNF139, Bcl-2, Bax, and caspase-3 were determined by immunohistochemistry, and
      apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labeling. SPSS 13.0 software was used for data processing and
      analyses, and significance was determined at P < 0.05. RESULTS: The expression of
      ZNF139 was stronger in tumors than in tumor-adjacent tissues (66.67% vs 44.44%; P
      < 0.01). Overexpression of ZNF139 correlated with tumor differentiation, invasion
      depth, clinical stage, lymphatic metastasis, and blood vessel invasion (all Ps <
      0.05). Patients with overexpression of ZNF139 had a poorer prognosis (P < 0.01),
      and overexpression of ZNF139 was an independent factor for the prognosis of GC
      patients by a Cox survival analysis (P = 0.02). A negative relationship between
      ZNF139 and the apoptosis index was observed (r = -0.686; P < 0.01). The
      expression of Bcl-2 in GC was stronger than in tumor-adjacent tissues (66.67% vs
      41.67%), whereas the expression levels of Bax and caspase-3 were lower in primary
      tumors (54.63% and 47.22%, respectively) than in tumor-adjacent tissues (73.15%
      and 73.15%, respectively) (all Ps < 0.05). The expression of ZNF139 negatively
      correlated with caspase-3 (r = -0.370; P < 0.01). The expressions of Bcl-2 and
      Bax were also negatively correlated (r = -0.231; P = 0.02). The expressions of
      caspase-3 and Bax protein were positively correlated (r = 0.217; P = 0.024).
      CONCLUSION: ZNF139 is related to clinicopathologic characteristics and prognosis
      of GC. Furthermore, it is overexpressed and involved in apoptosis in GC tissues
      by regulating caspase-3.

PMID- 25561802
TI  - T helper cell dysregulation with hepatitis B and rebalance with glucocorticoids.
AB  - AIM: To investigate T helper 17/regulatory T cell alterations in early severe
      hepatitis B and the effect of glucocorticoids. METHODS: The study included 20
      patients in the early stage of severe hepatitis B (SHB) and 11 healthy controls.
      All patients had elevated T helper 17 (Th17) levels, decreased regulatory T
      (Treg) cell levels, and significant Th17/Treg ratios. RESULTS: After
      glucocorticoid treatment, 16 patients showed improvement with significant
      decreases in Th17 levels, increases in Treg, and rebalanced Th17/Treg ratios. The
      four patients who showed no improvement had increases in both Th17 and Treg
      levels and an even higher Th17/Treg ratio than before. CONCLUSION: Glucocorticoid
      treatment can rectify Th17/Treg dysregulation in patients with SHB.

PMID- 25561803
TI  - Perceived risk as a barrier to appropriate diagnosis of irritable bowel syndrome.
AB  - AIM: To evaluate perceived risk, diagnostic testing, and acceptance of a
      diagnosis of irritable bowel syndrome (IBS) among the Korean laypersons. METHODS:
      We designed a conceptual framework to evaluate the health-seeking behavior of
      subjects based on a knowledge, attitude, and practice model. We developed a
      vignette-based questionnaire about IBS based on a literature review and focused
      group interviews. The vignette described a 40-year-old woman who meets the Rome
      III criteria for IBS without red-flag signs. It was followed by questions about
      demographic characteristics, health behaviors, IBS symptoms, risk perception,
      perceived need for diagnostic tests, and acceptance of a positive diagnosis of
      IBS. We planned a nationwide survey targeting laypersons without IBS and between
      the ages of 20 and 69 years. Survey participants were selected by quota sampling
      stratified by gender, age, and nationwide location. A multivariate logistic model
      was constructed based on literature reviews, univariate analysis, and a stepwise
      selection method to investigate correlations between the perceived risk, need for
      diagnostic tests, and acceptance of a positive diagnosis. RESULTS: Of 2354
      eligible households, 1000 subjects completed the survey and 983 subjects were
      analyzed, excluding those who met symptom criteria for IBS. After reading the IBS
      vignette, the majority of subjects (86.8%) responded that the patient was at
      increased risk of severe disease. The most frequent concern was colon cancer
      (59.8%), followed by surgical condition (51.5%). Most subjects responded the
      patient needs diagnostic tests (97.2%). Colonoscopy was the most commonly
      required test (79.5%). Less than half of the respondents requested a stool
      examination (45.0%), blood test (40.7%), abdominal ultrasound (36.0%), or
      computed tomography (20.2%). The subjects who felt increased risk were more
      likely to see a need for colonoscopy [adjusted odds ratio (aOR) = 2.10, 95%CI:
      1.38-3.18]. When asked about the positive diagnosis, the most frequent response
      was that "the patient would not be reassured" (65.7%). The increased risk
      perception group was less likely to be reassured by a positive diagnosis of IBS,
      compared to the other respondents (aOR = 0.52, 95%CI: 0.34-0.78). CONCLUSION: For
      IBS diagnosis, increased risk perception is a possible barrier to the appropriate
      use of diagnostic tests and to the patient's acceptance of a positive diagnosis.

PMID- 25561804
TI  - Prognosis of ulcerative colitis differs between patients with complete and
      partial mucosal healing, which can be predicted from the platelet count.
AB  - AIM: To determine the difference in clinical outcome between ulcerative colitis
      (UC) patients with Mayo endoscopic subscore (MES) 0 and those with MES 1.
      METHODS: UC patients with sustained clinical remission of 6 mo or more at the
      time of colonoscopy were examined for clinical outcomes and the hazard ratios of
      clinical relapse according to MES. Parameters, including blood tests, to identify
      predictive factors for MES 0 and slight endoscopic recurrence in clinically
      stable patients were assessed. Moreover, a receiver operating characteristic
      curve was generated, and the area under the curve was calculated to indicate the
      utility of the parameters for the division between complete and partial mucosal
      healing. All P values were two-sided and considered significant when less than
      0.05. RESULTS: A total of 183 patients with clinical remission were examined.
      Patients with MES 0 (complete mucosal healing: n = 80, 44%) were much less likely
      to relapse than those with MES 1 (partial mucosal healing: n = 89, 48%) (P <
      0.0001, log-rank test), and the hazard ratio of risk of relapse in patients with
      MES 1 vs MES 0 was 8.17 (95%CI: 4.19-17.96, P < 0.0001). The platelet count (PLT)
      < 26 * 10(4)/MUL was an independent predictive factor for complete mucosal
      healing (OR = 4.1, 95%CI: 2.15-7.99). Among patients with MES 0 at the initial
      colonoscopy, patients of whom colonoscopy findings shifted to MES 1 showed
      significant increases in PLT compared to those who maintained MES 0 (3.8 *
      10(4)/MUL vs -0.6 * 10(4)/MUL, P < 0.0001). CONCLUSION: The relapse rate differed
      greatly between patients with complete and partial mucosal healing. A shift from
      complete to partial healing in clinically stable UC patients can be predicted by
      monitoring PLT.

PMID- 25561805
TI  - Contrast-enhanced ultrasound in portal venous system aneurysms: a multi-center
      study.
AB  - AIM: To investigate contrast-enhanced ultrasound (CEUS) findings in portal venous
      system aneurysms (PVSAs). METHODS: In this multi-center, retrospective, case
      series study, we evaluated CEUS features of seven cases of PVSAs that were found
      incidentally on conventional ultrasound in the period 2007-2013. Three Ultrasound
      Centers were involved (Chieti, Italy, Bad Mergentheim, Germany, and Cluj-Napoca,
      Romania). All patients underwent CEUS with Sonovue((r)) (Bracco, Milan, Italy) at
      a standard dose of 2.4 mL, followed by 10 mL of 0.9% saline solution. The
      examinations were performed using multifrequency transducers and low mechanical
      index. We considered aneurysmal a focal dilatation of the portal venous system
      with a size that was significantly greater than the remaining segments of the
      same vein, and that was equal or larger than 21 mm for the extrahepatic segments
      of portal venous system, main portal vein and bifurcation, and 9 mm for the
      intrahepatic branches. RESULTS: After contrast agent injection, all PVSAs were
      not enhanced in the arterial phase (starting 8-22 s). All PVSAs were then rapidly
      enhanced in the early portal venous phase (starting three to five seconds after
      the arterial phase, 11-30 s), with persistence and slow washout of the contrast
      agent in the late phase (starting 120 s). In all patients, CEUS confirmed the
      presence of a "to-and-fro" flow by showing a swirling pattern within the
      dilatation in the early portal venous phase. CEUS also improved the delineation
      of the lumen, and was reliable in showing its patency degree and integrity of
      walls. In one patient, CEUS showed a partial enhancement of the lumen with a
      uniformly nonenhancing area in the portal venous and late phases, suggesting
      thrombosis. CONCLUSION: In our case series, we found that CEUS could be useful in
      the assessment and follow-up of a PVSA. Further studies are needed to validate
      its diagnostic accuracy.

PMID- 25561806
TI  - More patients should undergo surgery after sigmoid volvulus.
AB  - AIM: To assess the outcome of patients treated conservatively vs surgically
      during their first admission for sigmoid volvulus. METHODS: We conducted a
      retrospective study of 61 patients admitted to Aarhus University Hospital in
      Denmark between 1996 and 2011 for their first incidence of sigmoid volvulus. The
      condition was diagnosed by radiography, sigmoidoscopy or surgery. Patients
      treated with surgery underwent either a sigmoid resection or a percutaneous
      endoscopic colostomy (PEC). Conservatively treated patients were managed without
      surgery. Data was recorded into a Microsoft Access database and calculations were
      performed with Microsoft Excel. Kaplan-Meier plotting and Mantel-Cox (log-rank)
      testing were performed using GraphPad Prism software. Mortality was defined as
      death within 30 d after intervention or surgery. RESULTS: Among the total 61
      patients, 4 underwent emergency surgery, 55 underwent endoscopy, 1 experienced
      resolution of the volvulus after contrast enema, and 1 died without treatment
      because of large bowel perforation. Following emergency treatment, 28 patients
      underwent sigmoid resection (semi-elective n = 18; elective n = 10). Two patients
      who were unfit for surgery underwent PEC and both died, 1 after 36 d and the
      other after 9 mo, respectively. The remaining 26 patients were managed
      conservatively without sigmoid resection. Patients treated conservatively on
      their first admission had a poorer survival rate than patients treated surgically
      on their first admission (95%CI: 3.67-14.37, P = 0.036). Sixty-three percent of
      the 26 conservatively treated patients had not experienced a recurrence 3 mo
      after treatment, but that number dropped to 24% 2 years after treatment. Eight of
      the 14 patients with recurrence after conservative treatment had surgery with no
      30-d mortality. CONCLUSION: Surgically-treated sigmoid volvulus patients had a
      higher long-term survival rate than conservatively managed patients, indicating a
      benefit of surgical resection or PEC insertion if feasible.

PMID- 25561807
TI  - Increased expression of tumor necrosis factor-alpha is associated with advanced
      colorectal cancer stages.
AB  - AIM: To detect the expression of tumor necrosis factor-alpha (TNF-alpha) in
      colorectal cancer (CRC) cells among Saudi patients, and correlate its expression
      with clinical stages of cancer. METHODS: Archival tissue specimens were collected
      from 30 patients with CRC who had undergone surgical intervention at King Khalid
      University Hospital. Patient demographic information, including age and gender,
      tumor sites, and histological type of CRC, was recorded. To measure TNF-alpha
      mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed,
      paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse
      transcription polymerase chain reaction were performed. Colorectal tissue
      microarrays were constructed to investigate the protein expression of TNF-alpha
      by immunohistochemistry. RESULTS: The relative expression of TNF-alpha mRNA in
      colorectal cancer was significantly higher than that seen in adjacent normal
      colorectal tissue. High TNF-alpha gene expression was associated with Stage III
      and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty
      three percent of patients (25/30) showed strong TNF-alpha positive staining,
      while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30)
      were negative. We showed the presence of elevated TNF-alpha gene expression in
      cancer cells, which strongly correlated with advanced stages of tumor.
      CONCLUSION: High levels of TNF-alpha expression could be an independent
      diagnostic indicator of colorectal cancer, and targeting TNF-alpha might be a
      promising prognostic tool by assessment of the clinical stages of CRC.

PMID- 25561808
TI  - Evaluation of the 7th edition of the TNM classification in patients with resected
      esophageal squamous cell carcinoma.
AB  - AIM: To evaluate the prognostic factors and tumor stages of the 7(th) edition TNM
      classification for esophageal cancer. METHODS: In total, 1033 patients with
      esophageal squamous cell carcinoma (ESCC) who underwent surgical resection with
      or without (neo)adjuvant therapy between January 2003 and June 2012 at the
      Thoracic Surgery Department II of the Beijing Cancer Hospital, Beijing, China
      were included in this study. The following eligibility criteria were applied: (1)
      squamous cell carcinoma of the esophagus or gastroesophageal junction identified
      by histopathological examination; (2) treatment with esophagectomy plus
      lymphadenectomy with curative intent; and (3) complete pathologic reports and
      follow-up data. Patients who underwent non-curative (R1) resection and patients
      who died in hospital were excluded. Patients who received (neo)adjuvant therapy
      were also included in this analysis. All patients were restaged using the 7(th)
      edition of the Union for International Cancer Control and the American Joint
      Committee on Cancer TNM staging systems. Univariate and multivariate analyses
      were performed to identify the prognostic factors for survival. Survival curves
      were plotted using the Kaplan-Meier method, and the log-rank test was used to
      evaluate differences between the subgroups. RESULTS: Of the 1033 patients, 273
      patients received (neo)adjuvant therapy, and 760 patients were treated with
      surgery alone. The median follow-up time was 51.6 mo (range: 5-112 mo) and the
      overall 5-year survival rate was 36.4%. Gender, "pT" and "pN" descriptors,
      (neo)adjuvant therapy, and the 7(th) edition TNM stage grouping were independent
      prognostic factors in the univariate and multivariate analyses. However, neither
      histologic grade nor cancer location were independent prognostic factors in the
      univariate and multivariate analyses. The 5-year stage-based survival rates were
      as follows: IA, 84.9%; IB, 70.9%; IIA, 56.2%; IIB, 43.3%; IIIA, 37.9%; IIIB,
      23.3%; IIIC,12.9% and IV, 3.4%. There were significant differences between each
      adjacent staging classification. Moreover, there were significant differences
      between each adjacent pN and pM subgroup. According to the pT descriptor, there
      were significant differences between each adjacent subgroup except between pT3
      and pT4 (P = 0.405). However, there was no significant difference between each
      adjacent histologic grade subgroup and between each adjacent cancer location
      subgroup. CONCLUSION: The 7(th) edition is considered to be valid for patients
      with resected ESCC. However, the histologic grade and cancer location were not
      prognostic factors for ESCC.

PMID- 25561809
TI  - Clinicopathologic and prognostic relevance of ARID1A protein loss in colorectal
      cancer.
AB  - AIM: To explore the association between AT-rich interactive domain 1A (ARID1A)
      protein loss by immunohistochemistry and both clinicopathologic characteristics
      and prognosis in patients with colorectal cancer. METHODS: We retrospectively
      collected clinicopathologic data and archived paraffin-embedded primary
      colorectal cancer samples from 209 patients, including 111 patients with colon
      cancer and 98 patients with rectal cancer. The tumor stage ranged from stage I to
      stage IV according to the 7(th) edition of the American Joint Committee on Cancer
      tumor-node-metastasis (TNM) staging system. All patients underwent resection of
      primary colorectal tumors. The expression of ARID1A protein in primary colorectal
      cancer tissues was examined by immunohistochemical staining. The
      clinicopathologic association and survival relevance of ARID1A protein loss in
      colorectal cancer were analyzed. RESULTS: ARID1A loss by immunohistochemistry was
      not rare in primary colorectal cancer tumors (25.8%). There were 7.4%, 24.1%,
      22.2% and 46.3% of patients with ARID1A loss staged at TNM stage I, II, III and
      IV, respectively, compared with 20.0%, 22.6%, 27.7% and 29.7% of patients without
      ARID1A loss staged at TNM stage I, II, III and IV, respectively. In patients with
      ARID1A loss, the distant metastasis rate was 46.3%. However, only 29.7% of
      patients without ARID1A loss were found to have distant metastasis. In terms of
      pathologic differentiation, there were 25.9%, 66.7% and 7.4% with poorly,
      moderately and well differentiated tumors in patients with ARID1A loss, and
      14.2%, 72.3% and 13.5% with poorly, moderately and well differentiated tumors in
      patients without ARID1A loss, respectively. ARID1A loss was associated with late
      TNM stage (P = 0.020), distant metastasis (P = 0.026), and poor pathological
      classification (P = 0.035). However, patients with positive ARID1A had worse
      overall survival compared to those with negative ARID1A in stage IV colorectal
      cancer (HR = 2.49, 95%CI: 1.13-5.51). CONCLUSION: ARID1A protein loss is
      associated with clinicopathologic characteristics in colorectal cancer patients
      and with survival in stage IV patients.

PMID- 25561810
TI  - Efficacy of docetaxel combined with oxaliplatin and fluorouracil against stage
      III/IV gastric cancer.
AB  - AIM: To investigate the clinical efficacy and toxic effects of neoadjuvant
      chemotherapy using docetaxel combined with oxaliplatin and fluorouracil for
      treating stage III/IV gastric cancer. METHODS: A total of 53 stage III/IV gastric
      cancer patients were enrolled into the study and treated with neoadjuvant
      chemotherapy. Two of the cases were excluded. The program was as follows: 75
      mg/m(2) docetaxel and 85 mg/m(2) oxaliplatin on day 1 and 1500 mg/m(2)
      fluorouracil on days 1 to 3 for three weeks. RESULTS: The tumour changes,
      postoperative remission rate, changes in the symptoms and adverse reactions were
      observed. The overall clinical efficacy (complete remission + partial remission)
      of the neoadjuvant chemotherapy was 62.7%. R0 radical resection was performed on
      60.8% of the patients, with a remission rate (pathological complete response +
      pathological subtotal response + pathological partial response) of 74.2%. The
      Karnofksy score improved in 42 cases. The toxicity reactions mostly included
      myelosuppression, followed by gastrointestinal mucosal lesions, nausea, vomiting
      and diarrhoea. CONCLUSION: Neoadjuvant chemotherapy consisting of docetaxel
      combined with oxaliplatin and fluorouracil is effective for stage III/IV gastric
      cancer. However, the treatment is associated with a high incidence of bone marrow
      suppression, which should be managed clinically.

PMID- 25561811
TI  - Modified laparoscopic splenectomy and azygoportal disconnection combined with
      cell salvage is feasible and might reduce the need for blood transfusion.
AB  - AIM: To investigate perioperative outcomes in patients undergoing modified
      laparoscopic splenectomy and azygoportal disconnection (MLSD) with intraoperative
      autologous cell salvage. METHODS: We retrospectively evaluated outcomes in 79
      patients admitted to the Clinical Medical College of Yangzhou University with
      cirrhosis, portal hypertensive bleeding and secondary hypersplenism who underwent
      MLSD without (n = 46) or with intraoperative cell salvage and autologous blood
      transfusion, including splenic blood and operative hemorrhage (n = 33), between
      February 2012 and January 2014. Their intraoperative and postoperative variables
      were compared. These variables mainly included: operation time; estimated
      intraoperative blood loss; volume of allogeneic blood transfused; visual analog
      scale for pain on the first postoperative day; time to first oral intake; initial
      passage of flatus and off-bed activity; perioperative hemoglobin (Hb)
      concentration; and red blood cell concentration. RESULTS: There were no
      significant differences between the groups in terms of duration of surgery,
      estimated intraoperative blood loss and overall perioperative complication rate.
      In those receiving salvaged autologous blood, Hb concentration increased by an
      average of 11.2 +/- 4.8 g/L (P < 0.05) from preoperative levels by the first
      postoperative day, but it had fallen by 9.8 +/- 6.45 g/L (P < 0.05) in the group
      in which cell salvage was not used. Preoperative Hb was similar in the two groups
      (P > 0.05), but Hb on the first postoperative day was significantly higher in the
      autologous blood transfusion group (118.5 +/- 15.8 g/L vs 102.7 +/- 15.6 g/L, P <
      0.05). The autologous blood transfusion group experienced significantly fewer
      postoperative days of temperature > 38.0 degrees C (P < 0.05). CONCLUSION:
      Intraoperative cell salvage during MLSD is feasible and safe and may become the
      gold standard for liver cirrhosis with portal hypertensive bleeding and
      hypersplenism.

PMID- 25561812
TI  - Comparison of different gastric bypass procedures in gastric carcinoma patients
      with type 2 diabetes mellitus.
AB  - AIM: To determine the effect of different Roux-en-Y gastric bypass procedures in
      gastric carcinoma patients with type 2 diabetes mellitus. METHODS: A
      retrospective analysis of the clinical data of 54 patients with gastric cancer
      and type 2 diabetes mellitus treated in the Department of General Surgery from
      January 2006 to June 2013 was conducted. The patients underwent gastrectomy using
      different Roux-en-Y gastric bypass procedures (traditional, n = 26; modified, n =
      28). Fasting plasma glucose (FPG), two hour postprandial blood glucose (2 h PBG)
      and hemoglobin A1c (HbA1c) were analyzed before surgery (0 mo) and 1, 3 and 6 mo
      after surgery. RESULTS: FPG and 2 h PBG levels were significantly decreased 1 mo
      after surgery in the traditional Roux-en-Y gastric bypass group (FPG 7.5 +/- 1.3
      vs 10.7 +/- 1.2, P < 0.05) (2 h PBG 10.2 +/- 1.8 vs 13.8 +/- 3.2, P < 0.05). FPG
      and 2 h PBG levels were significantly decreased after surgery in the modified
      Roux-en-Y gastric bypass group (FPG 6.9 +/- 1.2 vs 10.5 +/- 1.1, 6.5 +/- 1.3 vs
      10.5 +/- 1.1, 6.4 +/- 1.2 vs 10.5 +/- 1.1, P < 0.05) (2 h PBG 9.9 +/- 2.2 vs 14.1
      +/- 2.9, 9.2 +/- 2.4 vs 14.1 +/- 2.9, 8.9 +/- 2.6 vs 14.1 +/- 2.9, P < 0.05).
      Compared with the levels before surgery, HbA1c levels were significantly
      decreased 3 and 6 mo after surgery (7.2 +/- 1.1 vs 10.5 +/- 1.1, 5.5 +/- 1.1 vs
      10.5 +/- 1.1, P < 0.05). Significant differences between the two groups regarding
      FPG, 2 h PBG and HbA1c concentration were observed 3 and 6 mo after surgery (FPG
      10.1 +/- 1.5 vs 6.5 +/- 1.3, 10.3 +/- 1.4 vs 6.4 +/- 1.2, P < 0.05) (2 h PBG 13.1
      +/- 2.8 vs 9.2 +/- 2.4, 13.6 +/- 3.1 vs 8.9 +/- 2.6, P < 0.05) (HbA1c 10.1 +/-
      1.4 vs 7.2 +/- 1.1, 10.5 +/- 1.3 vs 5.5 +/- 1.1, P < 0.05). CONCLUSION: Modified
      Roux-en-Y gastric bypass can improve glucose metabolism in type 2 diabetic
      patients with gastric cancer.

PMID- 25561813
TI  - Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional
      markers after acute pancreatitis.
AB  - AIM: To investigate impairment and clinical significance of exocrine and
      endocrine pancreatic function in patients after acute pancreatitis (AP). METHODS:
      Patients with AP were invited to participate in the study. Severity of AP was
      determined by the Atlanta classification and definitions revised in 2012.
      Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of
      fecal elastase-1. An additional work-up, including laboratory testing of serum
      nutritional markers for determination of malnutrition, was offered to all
      patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose
      tolerance tests were also performed in patients without prior diabetes mellitus,
      and type 3c diabetes mellitus (T3cDM) was diagnosed according to American
      Diabetes Association criteria. RESULTS: One hundred patients were included in the
      study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or
      more attacks. The most common etiology was alcohol. Mild, moderately severe and
      severe AP were present in 67, 15 and 18% of patients, respectively. The mean time
      from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in
      21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients
      with PEI, at least one serologic nutritional marker was below the lower limit of
      normal. T3cDM was more frequently present in patients with severe AP (P = 0.031),
      but was also present in some patients with mild and moderately severe AP. PEI was
      present in all degrees of severity of AP. There were no statistically
      significantly differences according to gender, etiology and number of AP attacks.
      CONCLUSION: As exocrine and endocrine pancreatic insufficiency can develop after
      AP, routine follow-up of patients is necessary, for which serum nutritional panel
      measurements can be useful.

PMID- 25561814
TI  - Assessment of the relationship between resilience and quality of life in patients
      with digestive cancer.
AB  - AIM: To study the relationship between resilience and quality of life (QOL) in
      patients with digestive cancer. METHODS: The resilience of patients was measured
      prior to treatment, and their psychological distress, fatigue status, and
      treatment side effects were assessed 3 wk after. Their QOL was measured after
      their treatment ended. A relationship model of these variables was constructed
      using path analysis. RESULTS: Resilience explained 33.2% of the variance in
      psychological distress, 16.1% of the variance in fatigue, and 1.23% of the
      variance in side effects. The relationship between resilience and QOL was
      statistically significant (beta = 0.119, t = 4.499, P < 0.001) when psychological
      distress, fatigue, and side effects were absent from the regression model,
      whereas the adjusted regression coefficient of resilience was not statistically
      significant (t = 1.562, P > 0.05) when these variables were added. Psychological
      distress, together with fatigue and side effects, could explain 52.40% of the
      variance in QOL (P < 0.05). Physiological distress accounted for 28.94% of the
      total effect on QOL, fatigue accounted for 33.72%, side effects accounted for
      22.53%, and resilience accounted for 14.80%. CONCLUSION: Resilience is not an
      independent predictor of QOL in patients with digestive cancer, but it is a main
      factor influencing psychological distress and side effects.

PMID- 25561815
TI  - Influence of high- and low-volume liver surgery in gallbladder carcinoma.
AB  - AIM: To clarify whether the performance of liver resections (LR) for incidental
      gallbladder carcinoma (IGBC)'s depends more on the experience of the hospitals in
      liver surgery than on complying with the guidelines in Germany. METHODS: For data
      analysis, we used the Surgical Association of Endoscopy and Ultrasound and
      Minimally Invasive Surgery Central Registry of "IGBC" of the German Society of
      Surgery (the German Registry). In 2010, we started a second form by requesting
      the frequency of LR at the various hospitals in Germany. The indication for LR
      was irrelevant. The aim was to determine the overall frequency of liver
      resections at the hospitals. We divided the hospitals according to their
      experience in liver surgery into high- (HV), mid- (MV), and low-volume (LV) LR
      hospitals. RESULTS: This study includes 487 IGBC's from 167 centers. There were
      36 high-volume, 32 mid-volume, and 99 low-volume centers. In the high-volume
      centers, the mean (range) number of liver resections was 101 (40-300). In the mid
      volume centers, the mean (range) number of liver resections was 26 (20-39). In
      the low-volume centers, the mean (range) number of liver resections was 6.5 (0
      19) (P < 0.001). LV's perform LR for T2-3 gallbladder carcinomas significantly
      less often than high-volume or mid-volume centers (chi(2) = 13.78, P = 0.001). In
      HV's and MV's, 61% of the patients with an indication for liver resection
      underwent LR, but in LV centers, only 41% with an indication for LR underwent LR
      (P < 0.001). In cases of T1b carcinomas, LR was performed significantly more
      often in HV's (P = 0.009). CONCLUSION: The central problem is that the
      performance of the required liver resection in IGBC in Germany depends on the
      hospital experience in liver surgery and not on the recommendations of the German
      guidelines.

PMID- 25561816
TI  - Treatment outcomes of chemotherapy between unresectable and recurrent biliary
      tract cancer.
AB  - AIM: To evaluate the differences in the treatment outcomes between the
      unresectable and recurrent biliary tract cancer patients who received
      chemotherapy. METHODS: Patients who were treated with gemcitabine and S-1
      combination therapy in the previous prospective studies were divided into groups
      of unresectable and recurrent cases. The tumor response, time-to-progression,
      overall survival, toxicity, and dose intensity were compared between these two
      groups. RESULTS: Response rate of the recurrent group was higher than that of the
      unresectable group (40.0% vs 25.5%; P = 0.34). Median time-to-progression of the
      recurrent and unresectable groups were 8.7 mo (95%CI), 1.2 mo, not reached) and
      5.7 mo (95%CI: 4.0-7.0 mo), respectively (P = 0.14). Median overall survival of
      the recurrent and the unresectable groups were 16.1 mo (95%CI: 2.0 mo-not
      reached) and 9.6 mo (95%CI: 7.1-11.7 mo), respectively (P = 0.10). Dose
      intensities were significantly lower in the recurrent groups (gemcitabine:
      recurrent group 83.5% vs unresectable group 96.8%; P < 0.01, S-1: Recurrent group
      75.9% vs unresectable group 91.8%; P < 0.01). Neutropenia occurred more
      frequently in recurrent group (recurrent group 90% vs unresectable group 55%; P =
      0.04). CONCLUSION: Not only the efficacy but also the toxicity and dose intensity
      were significantly different between unresectable and recurrent biliary tract
      cancer.

PMID- 25561817
TI  - Clinical trial with traditional Chinese medicine intervention ''tonifying the
      kidney to promote liver regeneration and repair by affecting stem cells and their
      microenvironment'' for chronic hepatitis B-associated liver failure.
AB  - AIM: To study the clinical efficacy of traditional Chinese medicine (TCM)
      intervention "tonifying the kidney to promote liver regeneration and repair by
      affecting stem cells and their microenvironment" ("TTK") for treating liver
      failure due to chronic hepatitis B. METHODS: We designed the study as a
      randomized controlled clinical trial. Registration number of Chinese Clinical
      Trial Registry is ChiCTR-TRC-12002961. A total of 144 patients with liver failure
      due to infection with chronic hepatitis B virus were enrolled in this randomized
      controlled clinical study. Participants were randomly assigned to the following
      three groups: (1) a modern medicine control group (MMC group, 36 patients); (2) a
      "tonifying qi and detoxification" ("TQD") group (72 patients); and (3) a
      "tonifying the kidney to promote liver regeneration and repair by affecting stem
      cells and their microenvironment" ("TTK") group (36 patients). Patients in the
      MMC group received general internal medicine treatment; patients in the "TQD"
      group were given a TCM formula "tonifying qi and detoxification" and general
      internal medicine treatment; patients in the "TTK" group were given a TCM formula
      of "TTK" and general internal medicine treatment. All participants were treated
      for 8 wk and then followed at 48 wk following their final treatment. The primary
      efficacy end point was the patient fatality rate in each group. Measurements of
      various virological and biochemical indicators served as secondary endpoints. The
      one-way analysis of variance and the t-test were used to compare patient outcomes
      in the different treatment groups. RESULTS: At the 48-wk post-treatment time
      point, the patient fatality rates in the MMC, "TQD", and "TTK" groups were
      51.61%, 35.38%, and 16.67%, respectively, and the differences between groups were
      statistically significant (P < 0.05). However, there were no significant
      differences in the levels of hepatitis B virus DNA or prothrombin activity among
      the three groups (P > 0.05). Patients in the "TTK" group had significantly higher
      levels of serum total bilirubin compared to MMC subjects (339.40 MUmol/L +/-
      270.09 MUmol/L vs 176.13 MUmol/L +/- 185.70 MUmol/L, P = 0.014). Serum albumin
      levels were significantly increased in both the "TQD" group and "TTK" group as
      compared with the MMC group (31.30 g/L +/- 4.77 g/L, 30.72 g/L +/- 2.89 g/L vs
      28.57 g/L +/- 4.56 g/L, P < 0.05). There were no significant differences in
      levels of alanine transaminase among the three groups (P > 0.05). Safety data
      showed that there was one case of stomachache in the "TQD" group and one case of
      gastrointestinal side effect in the "TTK" group. CONCLUSION: Treatment with "TTK"
      improved the survival rates of patients with liver failure due to chronic
      hepatitis B. Additionally, liver tissue was regenerated and liver function was
      restored.

PMID- 25561818
TI  - Reduced incidence and mortality from colorectal cancer with flexible
      sigmoidoscopy screening: a meta-analysis.
AB  - AIM: To conduct a systematic review and meta-analysis of published population
      based randomized controlled trials (RCTs). METHODS: RCTs evaluating the
      difference in mortality and incidence of colorectal cancer (CRC) between a
      screening flexible sigmoidoscopy (FS) group and control group (not assigned to
      screening FS) with a minimum 5 years median follow-up were identified by a search
      of MEDLINE and EMBASE databases and the Cochrane Central Register for Controlled
      Trials through August 2013. Random effects model was used for meta-analysis.
      RESULTS: Four RCTs with a total of 165659 patients in the FS group and 249707
      patients in the control group were included in meta-analysis. Intention-to-treat
      analysis showed that there was a 22% risk reduction in total incidence of CRC (RR
      = 0.78, 95%CI: 0.74-0.83), 31% in distal CRC incidence (RR = 0.69, 95%CI: 0.63
      0.75), and 9% in proximal CRC incidence (RR = 0.91, 95%CI: 0.83-0.99). Those who
      underwent screening FS were 18% less likely to be diagnosed with advanced CRC (OR
      = 0.82, 95%CI: 0.71-0.94). There was a 28% risk reduction in overall CRC
      mortality (RR = 0.72, 95%CI: 0.65-0.80) and 43% in distal CRC mortality (RR =
      0.57, 95%CI: 0.45-0.72). CONCLUSION: This meta-analysis suggests that screening
      FS can reduce the incidence of proximal and distal CRC and mortality from distal
      CRC along with reduction in diagnosis of advanced CRC.

PMID- 25561819
TI  - Non-operative successful management of a perforated small bowel diverticulum.
AB  - Jejunoileal diverticula are rare and generally asymptomatic. In the few cases of
      patients who develop complications such as diverticulitis, perforation,
      obstruction, and/or hemorrhage, conventional treatment consists of surgical
      resection. We describe a case of perforated jejunoileal diverticulum with
      localized abscess and highlight the merits of surgical vs medical management. The
      patient is a 77-year-old male who presented with sharp, constant abdominal pain
      just inferior to the umbilicus. Administration of intravenous antibiotics results
      in complete and long-term resolution of the patient's symptoms. In this report,
      we establish a framework for safely treating perforated small bowel diverticulum
      without surgical exploration. 

PMID- 25561820
TI  - Modified simultaneous integrated boost radiotherapy for an unresectable huge
      refractory pelvic tumor diagnosed as a rectal adenocarcinoma.
AB  - A clinical trial of radiotherapy with modified simultaneous integrated boost
      (SIB) technique against huge tumors was conducted. A 58-year-old male patient who
      had a huge pelvic tumor diagnosed as a rectal adenocarcinoma due to familial
      adenomatous polyposis was enrolled in this trial. The total dose of 77 Gy
      (equivalent dose in 2 Gy/fraction) and 64.5 Gy was delivered to the center of the
      tumor and the surrounding area respectively, and approximately 20% dose
      escalation was achieved with the modified SIB technique. The tumor with an
      initial maximum size of 15 cm disappeared 120 d after the start of the
      radiotherapy. Performance status of the patient improved from 4 to 0.
      Radiotherapy with modified SIB may be effective for patients with a huge tumor in
      terms of tumor shrinkage/disappearance, improvement of QOL, and prolongation of
      survival. 

PMID- 25561821
TI  - Colonic mucosa-associated lymphoid tissue lymphoma identified by chromoendoscopy.
AB  - Colonic mucosa-associated lymphoid tissue (MALT) lymphomas are a rare occurrence
      and the definitive treatment has not been established. Solitary or multiple,
      elevated or polypoid lesions are the usual appearances of MALT lymphoma in the
      large intestine and sometimes the surface may reveal abnormal vascularity.
      Herein, we report a case of MALT lymphoma and review the relevant literature.
      Upon colonoscopy, a suspected pathologic lesion was observed in the proximal
      transverse colon. The lesion could be distinguished more prominently after using
      narrow-band imaging mode and indigo carmine-dye spraying chromoendoscopy.
      Histopathologic examination of this biopsy specimen revealed lymphoepithelial
      lesions with diffuse proliferation of atypical lymphoid cells effacing the
      glandular architecture and centrocyte-like cells infiltrating the lamina propria.
      Immunohistochemical analyses showed that tumor cells were positive for CD20 and
      Bcl-2e, and negative for CD10, CD23, and Bcl-6. According to Ann-Arbor staging
      system, the patient had stage IIE. A partial colectomy with dissection of the
      paracolic lymph nodes was performed. Until now, there is no recurrence of
      lymphoma at follow-up. 

PMID- 25561823
TI  - ''Sandwich'' treatment for diospyrobezoar intestinal obstruction: a case report.
AB  - Intestinal obstruction is a common clinical entity encountered in surgical
      practice. The objective of this report is to corroborate an atypical scenario of
      intestinal obstruction in a Chinese patient and to focus on the diagnosis and
      treatment. A 27-year-old male presented with a history of gastric pain combined
      with nausea and abdominal distension that had been present for 5 d. The presence
      of a foreign body was detected by computed tomography and observed as an abnormal
      density within the stomach. A diospyrobezoar was revealed during gastroscopy, the
      extraction of which was prevented due to its size and firmness. An endoscopic
      holmium laser joined with a snare was used to fragment the obstruction, which was
      followed by management with a conservative "sandwich" treatment strategy
      involving intestinal decompression with an ileus tube and Coca-Cola lavage
      between endoscopic lithotripsy fragmentation procedures. This strategy resulted
      in the successful removal of the diospyrobezoar along with multiple small bowel
      obstructions. The patient was discharged after abatement of symptoms. The case
      presented here demonstrates the implementation of a conservative, yet successful,
      treatment as an alternative to conventional surgical removal of intestinal
      obstructions. 

PMID- 25561822
TI  - Renal aspergillosis after liver transplantation: clinical and imaging
      manifestations in two cases.
AB  - Renal aspergillosis (RAsp) is a rare complication in liver transplant (LT)
      recipients. Here we report RAsp in two LT recipients. In both patients, RAsp
      occurred more than 90 d after allogenetic orthotropic LT, and all the clinical
      findings were unspecific. RAsp involved unilateral kidney in Case one and
      bilateral kidneys in Case two. Both computed tomography (CT) and magnetic
      resonance imaging (MRI) revealed renal abscesses, with progressively enhanced
      walls and separations and unenhanced alveolate areas after contrast agent
      administration. On unenhanced CT images they showed inhomogeneous hypo
      attenuation. On fat-suppressed T2-weighted images (T2WIs), the walls and
      separations of the abscesses showed slightly low signal intensity and the central
      parts of the lesions showed slightly high signal intensity. Both on CT and MRI,
      there were some hints of renal infarction or chronic ischemia. Both cases were
      treated by radical nephrectomy followed by adjuvant antifungal treatment. They
      all recovered well. 

PMID- 25561824
TI  - Untreated atrial fibrillation in the United States of America: Understanding the
      barriers and treatment options.
AB  - Atrial fibrillation is the most commonly treated arrhythmia in the United States
      of America. Stroke is the most devastating consequence of atrial fibrillation.
      For decades, warfarin has been the most recommended treatment for patients with
      atrial fibrillation at risk for stroke and systemic emboli. However, many
      patients at risk are not treated with anticoagulants. Several reasons exist,
      including physician underestimation of patient stroke risk, physician
      overestimation of bleeding risk, and patients' reluctance to take chronic
      warfarin due to the difficulties of this medication in relation to its
      pharmacokinetics and interactions with food and other medications. Risk scores
      have helped to better define patient risks and benefits from chronic
      anticoagulation. Novel anticoagulants (NOACs) have improved the ability for
      patients to be compliant with anticoagulation. 

PMID- 25561825
TI  - Effects of Online Comments on Smokers' Perception of Anti-Smoking Public Service
      Announcements.
AB  - On YouTube anti-smoking PSAs are widely viewed and uploaded; they also receive
      extensive commentary by viewers. This study examined whether such evaluative
      comments with or without uncivil expressions influence evaluations by subsequent
      viewers. Results showed PSAs with positive (i.e. anti-smoking) comments were
      perceived by smokers as more effective than PSAs with negative (pro smoking)
      comments. Smokers in the no comment condition gave the highest perceived
      effectiveness score to PSAs. Smokers' readiness to quit smoking moderated the
      effect of comments on PSA evaluation. Smokers reading negative uncivil comments
      reported more negative attitude toward quitting and a lower level of perceived
      risk of smoking than those reading negative civil comments but positive civil and
      positive uncivil comments didn't elicit different responses.

PMID- 25561826
TI  - The family Carabodidae (Acari, Oribatida) VIII. The genus Machadocepheus (first
      part) Machadocepheusleoneae sp. n. and Machadocepheusrachii sp. n. from Gabon.
AB  - The genus Machadocepheus, being one of the more complex genera of the Carabodidae
      family, is briefly outlined to demonstrate this complexity. Descriptions of two
      new species from Gabon, Machadocepheusleoneae sp. n. and Machadocepheusrachii sp.
      n. are given. 

PMID- 25561827
TI  - Genetic utility of natural history museum specimens: endangered fairy shrimp
      (Branchiopoda, Anostraca).
AB  - We examined the potential utility of museum specimens as a source for genetic
      analysis of fairy shrimp. Because of loss of their vernal pool habitat, some
      fairy shrimp (including Branchinectasandiegonensis and Branchinectalynchi) are
      listed as threatened or endangered in Southern California by the United States
      Fish and Wildlife Service. Management of those species requires extensive
      population genetics studies and the resolution of important genetic complexity
      (e.g. possible hybridization between endangered and non-endangered species).
      Regulations mandating deposition of specimens of listed species have resulted in
      thousands of specimens accessioned into the Natural History Museum of Los Angeles
      County that have been preserved in a variety of solutions. We subsampled those
      specimens, as well as other Anostraca with known collection and preservation
      histories, to test their potential for genetic analysis by attempting DNA
      extraction and amplification for mt16SrDNA. Fixation and preservation in not
      denatured ethanol had a far greater sequencing success rate than other (and
      unknown) fixatives and preservatives. To maximize scientific value we recommend
      field preservation in 95% not denatured ethanol (or, if pure ethanol is
      unavailable, high-proof drinking spirits, e.g. EverclearTM, or 151 proof white
      rum), followed by storage in 95% not denatured ethanol. 

PMID- 25561828
TI  - Diversity of the free-living marine and freshwater Copepoda (Crustacea) in Costa
      Rica: a review.
AB  - The studies on marine copepods of Costa Rica started in the 1990's and focused on
      the largest coastal-estuarine systems in the country, particularly along the
      Pacific coast. Diversity is widely variable among these systems: 40 species have
      been recorded in the Culebra Bay influenced by upwelling, northern Pacific coast,
      only 12 in the Gulf of Nicoya estuarine system, and 38 in Golfo Dulce, an anoxic
      basin in the southern Pacific coast of the country. Freshwater environments of
      Costa Rica are known to harbor a moderate diversity of continental copepods (25
      species), which includes 6 calanoids, 17 cyclopoids and only two harpacticoids.
      Of the +100 freshwater species recorded in Central America, six are known only
      from Costa Rica, and one appears to be endemic to this country. The freshwater
      copepod fauna of Costa Rica is clearly the best known in Central America.
      Overall, six of the 10 orders of Copepoda are reported from Costa Rica. A
      previous summary by 2001 of the free-living copepod diversity in the country
      included 80 marine species (67 pelagic, 13 benthic). By 2009, the number of
      marine species increased to 209: 164 from the Pacific (49% of the copepod fauna
      from the Eastern Tropical Pacific) and 45 from the Caribbean coast (8% of species
      known from the Caribbean Basin). Both the Caribbean and Pacific species lists are
      growing. Additional collections of copepods at Cocos Island, an oceanic island
      530 km away of the Pacific coast, have revealed many new records, including five
      new marine species from Costa Rica. Currently, the known diversity of marine
      copepods of Costa Rica is still in development and represents up to 52.6% of the
      total marine microcrustaceans recorded in the country. Future sampling and
      taxonomic efforts in the marine habitats should emphasize oceanic environments
      including deep waters but also littoral communities. Several Costa Rican records
      of freshwater copepods are likely to represent undescribed species. Also, the
      biogeographic relevance of the inland copepod fauna of Costa Rica requires more
      detailed surveys. 

PMID- 25561829
TI  - A new species of the genus Nihonotrypaea Manning & Tamaki, 1998 (Crustacea,
      Decapoda, Axiidea, Callianassidae) from the South China Sea.
AB  - A new species of the genus Nihonotrypaea Manning & Tamaki, 1998,
      Nihonotrypaeahainanensis sp. n., collected from the South China Sea, is described
      and illustrated. It is distinguishable from Nihonotrypaeaharmandi (Bouvier,
      1901), Nihonotrypaeajaponica (Ortmann, 1891), Nihonotrypaeathermophila Lin, Komai
      & Chan, 2007 and Nihonotrypaeamakarovi Martin, 2013 by having the elongated
      carpus of the male and female major cheliped. The new species is distinguishable
      from Nihonotrypaeapetalura (Stimpson, 1860) by the proximolower margin of the
      carpus of the male major cheliped bearing several small denticles. 

PMID- 25561830
TI  - Crustaceans from antipatharians on banks of the northwestern Gulf of Mexico.
AB  - The stalked barnacle Oxynaspisgracilis, the chirostylid squat lobster Uroptychus
      sp., and the caridean shrimps Periclimenescf.antipathophilus and
      Pseudopontonidesprincipis have been collected at 68-124 m by a remotely operated
      vehicle (ROV) on banks in the northern Gulf of Mexico. These species inhabited
      six species of antipatharian hosts. Pseudopontonidesprincipis, Oxynaspisgracilis,
      and Uroptychus sp. were not confined to a single host species. Except for
      Oxynaspisgracilis, collected by ROV in 2004-2005, these species have not been
      reported previously in the northwestern Gulf of Mexico. 

PMID- 25561832
TI  - Molecular and morphological differentiation between two Miocene-divergent
      lineages of Amazonian shrimps, with the description of a new species (Decapoda,
      Palaemonidae, Palaemon).
AB  - Palaemoncarteri (Gordon, 1935) and Palaemonivonicus (Holthuis, 1950) are
      morphologically similar species of South American freshwater shrimps. Past
      studies have questioned the taxonomic status of both species, which are supposed
      to have partially sympatric geographic distributions in the Amazon basin. We
      analyzed a 550 bp fragment of the mitochondrial 16S rRNA gene from these
      Amazonian Palaemon species as well as from 11 palaemonids as the outgroup.
      Additionally, we checked diagnostic characters of the genus and family as well as
      other morphological characters that have been little explored before.
      Palaemoncarteri and Palaemonivonicus are allocated in two sister lineages, with
      wide genetic divergence and little morphological differentiation. The divergence
      time between these lineages was estimated as approximately 10 million years ago.
      Both molecular and morphological data support the taxonomic validity of both
      Palaemoncarteri and Palaemonivonicus, refuting the hypothesis of synonymy. In
      addition, a new species, Palaemonyuna sp. n., closely related to
      Palaemonivonicus, is described. Our findings indicate that these species can be
      differentiated using the projection of the anterolateral margin and anterolateral
      spine of the first antennular segment, shape of the rostrum, and relative size of
      the appendix masculina. 

PMID- 25561831
TI  - Grooming as a secondary behavior in the shrimp Macrobrachiumrosenbergii
      (Crustacea, Decapoda, Caridea).
AB  - The giant freshwater prawn, Macrobrachiumrosenbergii, is a large shrimp
      extensively used in aquaculture whose grooming behaviors were analyzed in this
      study. Macrobrachiumrosenbergii exhibits three unique male morphotypes that
      differ in their behavior, morphology and physiology: small-clawed males (SM),
      orange-clawed males (OC) and blue-clawed males (BC). The largest and most
      dominant males, BC males, are predicted to have significantly different grooming
      behaviors compared to females and the other two male morphotypes. These BC males
      may be too large and bulky to efficiently groom and may dedicate more time to
      mating and agonistic interactions than grooming behaviors. Observations were
      conducted to look at the prevalence of grooming behaviors in the absence and
      presence of conspecifics and to determine if any differences in grooming behavior
      exist among the sexes and male morphotypes. Significant differences in the
      grooming behaviors of all individuals (females and male morphotypes) were found.
      BC males tended to have the highest grooming time budget (percent of time spent
      grooming) while SM males had a relatively low grooming time budget. The grooming
      behaviors of the male morphotypes differed, indicating while these males play
      distinct, separate roles in the social hierarchy, they also have different
      grooming priorities. The conditions in which Macrobrachiumrosenbergii are
      cultured may result in increased body fouling, which may vary, depending on the
      grooming efficiencies and priorities of these male morphotypes. Overall, grooming
      behaviors were found to be a secondary behavior which only occurred when primary
      behaviors such as mating, feeding or fighting were not present. 

PMID- 25561833
TI  - Molecular perspective on the American transisthmian species of Macrobrachium
      (Caridea, Palaemonidae).
AB  - The closure of the Isthmus of Panama (about 3.1 million years ago) separated
      previously continuous populations and created two groups of extant species, which
      live now in the Pacific and Atlantic drainage systems. This relatively recent
      event was a trigger to diversification of various species in the Neotropics,
      nonetheless there are exemplars that do not show sufficient morphologic
      variability to separate them by traditional morphological tools. About 60 years
      ago, some freshwater decapod species with high morphological similarity were
      separate by previous researchers, based on geographical distribution, in Pacific
      and Atlantic and considered as "sister species". However, the complete isolation
      of these prawns by this geographical barrier is questionable, and it has
      generated doubts about the status of the following transisthmian pairs of sibling
      species: Macrobrachiumoccidentale * Macrobrachiumheterochirus,
      Macrobrachiumamericanum * Macrobrachiumcarcinus, Macrobrachiumdigueti *
      Macrobrachiumolfersii, Macrobrachiumhancocki * Macrobrachiumcrenulatum,
      Macrobrachiumtenellum * Macrobrachiumacanthurus and Macrobrachiumpanamense *
      Macrobrachiumamazonicum. Here we evaluated the relation among these pairs of
      sibling species in a molecular phylogenetic context. We generated 95 new
      sequences: 26 sequences of 16S rDNA, 25 of COI mtDNA and 44 of 18S nDNA. In
      total, 181 sequences were analyzed by maximum likelihood phylogenetic method,
      including 12 Macrobrachium transisthmian species, as well as seven other American
      Macrobrachium species, and two other palaemonids. Our analysis corroborated the
      morphological proximity of the sibling species. Despite the high degree of
      morphological similarities and considerable genetic diversification encountered
      among the transisthmian sister species, our data support the conclusion that all
      species included in sibling groups studied herein are valid taxonomic entities,
      but not all pairs of siblings form natural groups. 

PMID- 25561834
TI  - Results of the global conservation assessment of the freshwater crabs (Brachyura,
      Pseudothelphusidae and Trichodactylidae): The Neotropical region, with an update
      on diversity.
AB  - The freshwater crabs of the Neotropics comprise 311 species in two families
      (Pseudothelphusidae and Trichodactylidae) and one or both of these families are
      found in all of the countries in the Neotropical region (except for Chile and
      some of the Caribbean islands). Colombia (102 species, 81% endemic) and Mexico
      (67 species, 95% endemic) are the biodiversity hotspots of freshwater crab
      species richness and country-level endemism for this region. The results of the
      IUCN Red List conservation assessments show that 34% of pseudothelphusids and 10%
      of trichodactylids have an elevated risk of extinction, 29% of pseudothelphusids
      and 75% of trichodactylids are not at-risk (Least Concern), and although none are
      actually extinct, 56% of pseudothelphusids and 17% of trichodactylids are too
      poorly known to assess (Data Deficient). Colombia (14 species), Venezuela (7
      species), Mexico (6 species), and Ecuador (5 species) are the countries with the
      highest number of threatened species of Neotropical freshwater crabs. The
      majority of threatened species are restricted-range semiterrestrial endemics
      living in habitats subjected to deforestation, alteration of drainage patterns,
      and pollution. This underlines the need to prioritize and develop conservation
      measures before species decline to levels from which they cannot recover. These
      results represent a baseline that can be used to design strategies to save
      threatened Neotropical species of freshwater crabs. 

PMID- 25561835
TI  - Relative growth and morphological sexual maturity size of the freshwater crab
      Trichodactylusborellianus (Crustacea, Decapoda, Trichodactylidae) in the Middle
      Parana River, Argentina.
AB  - The relative growth of a number of morphological dimensions of the South American
      freshwater crab Trichodactylusborellianus (Trichodactylidae) were compared and
      related to sexual dimorphism. Crabs were collected from ponds in the Middle
      Parana River in Argentina. A regression model with segmented relationship was
      used to test for relative growth between these measurements where breakpoints
      infer the body size at which crabs reach sexual maturity. In both sexes the
      carapace width and the length, height, and thickness of the right and left chelae
      were measured, as well as the male pleopod length and the female abdomen width.
      All of these measurements were found to show positive allometry with the
      exception of the male pleopod length and the left chelae, which did not show a
      breakpoint. In females the breakpoint for the abdomen width inferred a
      morphological sexual maturity at carapace width 6.9 mm. In males the break point
      for the pleopod length was at carapace width 6.6 mm, with that for the chelae
      measurements was between carapace widths 6.4 and 6.9 mm. The relative growth
      pattern in Trichodactylusborellianus was found to be similar to that recorded for
      other species of the family Trichodactylidae. 

PMID- 25561836
TI  - Morphological variation of freshwater crabs Zilchiopsiscollastinensis and
      Trichodactylusborellianus (Decapoda, Trichodactylidae) among localities from the
      middle Parana River basin during different hydrological periods.
AB  - Measures of hydrologic connectivity have been used extensively to describe
      spatial connections in riverine landscapes. Hydrologic fluctuations constitute an
      important macrofactor that regulates other environmental variables and can
      explain the distribution and abundance of organisms. We analysed morphological
      variations among individuals of two freshwater crab species,
      Zilchiopsiscollastinensis and Trichodactylusborellianus, from localities of the
      middle Parana River basin during two phases of the local hydrological regime.
      Specimens were sampled at sites (localities) of Parana River, Saladillo Stream,
      Salado River and Coronda River when water levels were falling and rising. The
      conductivity, pH, temperature and geographical coordinates were recorded at each
      site. The dorsal cephalothorax of each crab was represented using 16 landmarks
      for Zilchiopsiscollastinensis and 14 landmarks for Trichodactylusborellianus. The
      Canonical Variate Analyses showed differences in shape (for both species) among
      the crabs collected from the Parana and Salado Rivers during the two hydrologic
      phases. We did not find a general distribution pattern for shape among the crab
      localities. During falling water, the shapes of Zilchiopsiscollastinensis were
      not related to latitude-longitude gradient (i.e., showing greater overlap in
      shape), while during rising water the shapes were ordered along a distributional
      gradient according to geographical location. Contrary, shapes of
      Trichodactylusborellianus were related to latitude-longitude during falling water
      and were not related to distributional gradient during rising water. The
      cephalothorax shape showed, in general, no statistically significant covariations
      with environmental variables for either species. These results show that each
      freshwater crab species, from different localities of the middle Parana River,
      remain connected; however, these connections change throughout the hydrologic
      regime of the floodplain system. This study was useful for delineating how the
      relation among shapes of crabs of localities varies during two phases of the
      hydrological regime and for estimating the connections and geographical patterns
      in the floodplain system. 

PMID- 25561837
TI  - Inferences on mating and sexual systems of two Pacific Cinetorhynchus shrimps
      (Decapoda, Rhynchocinetidae) based on sexual dimorphism in body size and cheliped
      weaponry.
AB  - Sexual dimorphism in body size and weaponry was examined in two Cinetorhynchus
      shrimp species in order to formulate hypotheses on their sexual and mating
      systems. Collections of Cinetorhynchus sp. A and Cinetorhynchus sp. B were made
      in March, 2011 on Coconut Island, Hawaii, by hand dipnetting and minnow traps in
      coral rubble bottom in shallow water. Although there is overlap in male and
      female size, some males are much larger than females. The major (pereopod 1)
      chelipeds of males are significantly larger and longer than those of females. In
      these two Cinetorhynchus species, males and females have third maxillipeds of
      similar relative size, i.e., those of males are not hypertrophied and probably
      not used as spear-like weapons as in some other rhynchocinetid (Rhynchocinetes)
      species. Major chelae of males vary with size, changing from typical female-like
      chelae tipped with black corneous stout setae to subchelate or prehensile
      appendages in larger males. Puncture wounds or regenerating major chelipeds were
      observed in 26.1 % of males examined (N = 38 including both species). We
      interpret this evidence on sexual dimorphism as an indication of a temporary male
      mate guarding or "neighborhoods of dominance" mating system, in which larger
      dominant robustus males defend females and have greater mating success than
      smaller males. Fecundity of females increased with female size, as in most
      caridean species (500-800 in Cinetorhynchus sp. A; 300-3800 in Cinetorhynchus sp.
      B). Based on the sample examined, we conclude that these two species have a
      gonochoric sexual system (separate sexes) like most but not all other
      rhynchocinetid species in which the sexual system has been investigated. 

PMID- 25561838
TI  - Reproductive biology of the sea anemone shrimp Periclimenesrathbunae (Caridea,
      Palaemonidae, Pontoniinae), from the Caribbean coast of Costa Rica.
AB  - Caridean shrimps are a highly diverse group and many species form symbiotic
      relationships with different marine invertebrates. Periclimenesrathbunae is a
      brightly colored shrimp that lives predominantly in association with sea
      anemones. Information about the reproductive ecology of the species is scarce.
      Therefore, we collected 70 ovigerous females inhabiting the sun sea anemone
      Stichodactylahelianthus in coral reefs from the southern Caribbean coast of Costa
      Rica. Females produced on average 289 +/- 120 embryos. The volume of recently
      produced embryos was on average 0.038 mm(3), and embryo volume increased by 192%
      during the incubation period. The average embryo mortality during embryogenesis
      was 24%. The reproductive output was 0.24 +/- 0.094, considerably higher than in
      many other pontoniine shrimps. Females carrying embryos close to hatching showed
      fully developed ovaries, suggesting consecutive spawning. We assume that the
      sheltered habitat, living on sea anemones, allows Periclimenesrathbunae to
      allocate more energy in embryo production than most other free-living caridean
      shrimps. This is the first record of Periclimenesrathbunae for Costa Rica. 

PMID- 25561839
TI  - Embryo production in the sponge-dwelling snapping shrimp Synalpheusapioceros
      (Decapoda, Alpheidae) from Bocas del Toro, Panama.
AB  - Caridean shrimps of the genus Synalpheus are abundant and widely distributed in
      tropical and subtropical regions, but knowledge of their reproductive biology
      remains scarce. We report reproductive traits of Synalpheusapioceros from Bocas
      del Toro, Panama, based on collections in August 2011. The 46 ovigerous females
      that were analyzed ranged in size from 3.8 to 7.4 mm in carapace length.
      Fecundity varied between 8 and 310 embryos and increased with female size.
      Females invested 18.6 +/- 10.3% of their body weight in Embryo production. Embryo
      volume increased considerably (77.2%) during embryogenesis, likely representing
      water uptake near the end of incubation period. Compared to Synalpheus species
      with abbreviated or direct development, Synalpheusapioceros produced
      substantially smaller embryos; however, Synalpheusapioceros seems to have a
      prolonged larval phase with at least five zoeal stages, which may explain the
      combination of relatively small and numerous embryos. We did not find nonviable,
      minute, chalky embryos, previously reported for Synalpheusapioceros specimens
      obtained from the northwestern Gulf of Mexico, which supports the hypothesis that
      the production of this type of embryos may be a physiological response of this
      warm-water species to the temperature decrease near to its latitudinal range
      limit. 

PMID- 25561840
TI  - Reproductive traits of the symbiotic pea crab Austinotheresangelicus (Crustacea,
      Pinnotheridae) living in Saccostreapalmula (Bivalvia, Ostreidae), Pacific coast
      of Costa Rica.
AB  - Pea crabs of the family Pinnotheridae exhibit a symbiotic life style and live
      associated with a variety of different marine organisms, especially bivalves.
      Despite the fact that pea crabs can cause serious problems in bivalve
      aquaculture, the available information about the ecology of these crabs from
      Central America is extremely limited. Therefore, the present study aimed to
      describe different reproductive features of the pinnotherid crab
      Austinotheresangelicus associated with the oyster Saccostreapalmula in the Golfo
      de Nicoya, Pacific coast of Costa Rica. Monthly sampling was conducted from April
      to December 2012. Average carapace width (CW) of the 47 analyzed ovigerous
      females was 7.62 mm. The species produced on average 2677 +/- 1754 recently 
      extruded embryos with an average volume of 0.020 +/- 0.003 mm(3); embryo volume
      increased during embryogenesis by 21%, but did not vary significantly between
      developmental stages. Brood mass volume varied greatly (between 11.7 and 236.7
      mm(3)), and increased significantly with female CW. Females invested on average
      76.7% (minimum: 21.7%; maximum: 162.8%) of their body weight in brood production,
      which confirms a substantially higher energy allocation for embryo production in
      pinnotherid crabs compared to free-living decapods. 

PMID- 25561841
TI  - Population structure, sex ratio and growth of the seabob shrimp
      Xiphopenaeuskroyeri (Decapoda, Penaeidae) from coastal waters of southern Brazil.
AB  - This study evaluated the growth and population structure of Xiphopenaeuskroyeri
      in Babitonga Bay, southern Brazil. Monthly trawls were conducted from July 2010
      through June 2011, using a shrimp boat outfitted with double-rig nets, at depths
      from 5 to 17 m. Differences from the expected 0.5 sex ratio were determined by
      applying a Binomial test. A von Bertalanffy growth model was used to estimate the
      individual growth, and longevity was calculated using its inverted formula. A
      total of 4,007 individuals were measured, including 1,106 juveniles (sexually
      immature) and 2,901 adults. Females predominated in the larger size classes.
      Males and females showed asymptotic lengths of 27.7 mm and 31.4 mm, growth
      constants of 0.0086 and 0.0070 per day, and longevities of 538 and 661 days,
      respectively. The predominance of females in larger size classes is the general
      rule in species of Penaeidae. The paradigm of latitudinal-effect does not appear
      to apply to seabob shrimp on the southern Brazilian coast, perhaps because of the
      small proportion of larger individuals, the occurrence of cryptic species, or the
      intense fishing pressure in this region. The longevity values are within the
      general range for species of Penaeidae. The higher estimates for longevity in
      populations at lower latitudes may have occurred because of the growth constants
      observed at these locations, resulting in overestimation of this parameter. 

PMID- 25561842
TI  - Inferring population connectivity across the range of distribution of the
      stiletto shrimp Artemesialonginaris Spence Bate, 1888 (Decapoda, Penaeidae) from
      DNA barcoding: implications for fishery management.
AB  - Artemesialonginaris is a marine shrimp endemic to the southwestern Atlantic and
      distributed from Atafona, Rio de Janeiro (Brazil) to Rawson, Chubut (Argentina).
      In recent years, this species has become an important target of the commercial
      fishery as a consequence of the decline in the fishery of more traditional and
      profitable marine shrimps. In addition, phenotypic variations have been
      documented in populations along its distribution. Therefore, investigations on
      the genetics of the fishing stocks are necessary for the development of
      sustainable management strategies and for understanding the possible sources of
      these variations. The mitochondrial gene Cytochrome Oxidase I (COI) was used to
      search for evidence of genetic structure among the populations of
      Artemesialonginaris and to analyze the phylogenetic relationships among them. A
      total of 60 specimens were collected from seven different localities, covering
      its geographical range. The final alignment showed 53 haplotypes (48 individuals
      and 5 shared), with no biogeographical pattern. The low genetic divergence found,
      with a non-significant FST value, also suggests the absence of population
      structure for this gene. These findings indicate a continuous gene flow among the
      populations analyzed, suggesting that the phenotypic variation is a consequence
      of different environmental conditions among the localities. 

PMID- 25561843
TI  - Differences in life-history and ecological traits between co-occurring Panulirus
      spiny lobsters (Decapoda, Palinuridae).
AB  - Coexistence of closely related species may be promoted by niche differentiation
      or result from interspecific trade-offs in life history and ecological traits
      that influence relative fitness differences and contribute to competitive
      inequalities. Although insufficient to prove coexistence, trait comparisons
      provide a first step to identify functional differences between co-occurring
      congeneric species in relation to mechanisms of coexistence. Here, a comparative
      review on life history and ecological traits is presented for two pairs of co
      occurring species of spiny lobsters in the genus Panulirus: Panulirusgracilis and
      Panulirusinflatus from the Eastern Central Pacific region, and Panulirusargus and
      Panulirusguttatus from the Caribbean region. Panulirusgracilis and
      Panulirusinflatus have similar larval, postlarval, and adult sizes and a similar
      diet, but differ in degree of habitat specialization, fecundity, and growth rate.
      However, little is known on behavioral traits of these two species that may
      influence their competitive abilities and susceptibility to predators. The more
      abundant information on Panulirusargus and Panulirusguttatus shows that these two
      species differ more broadly in degree of habitat specialization, larval,
      postlarval and adult sizes, diet, fecundity, growth rate, degree of sociality,
      defense mechanisms, susceptibility to predators, and chemical ecology, suggesting
      a greater degree of niche differentiation between Panulirusargus and
      Panulirusguttatus than between Panulirusgracilis and Panulirusinflatus. Whether
      the substantial niche differentiation and apparent interspecific trade-offs
      between Panulirusargus and Panulirusguttatus relative to Panulirusgracilis and
      Panulirusinflatus reflect an earlier divergence of the former pair of species in
      the evolution of the genus constitutes an intriguing hypothesis. However, whether
      or not post-divergence evolution of each species pair occurred in sympatry
      remains uncertain. 

PMID- 25561844
TI  - Reference values for feeding parameters of isopods (Porcellioscaber, Isopoda,
      Crustacea).
AB  - The advantage of using terrestrial isopods in toxicity studies is that a battery
      of parameters can be tested at different levels of biological complexity. Feeding
      parameters for example link organism level response to potential ecological
      consequences but a problem with using feeding parameters in toxicity tests with
      terrestrial isopods is their high variability. The aim of our study was to set
      benchmark values for feeding parameters for isopod Porcellioscaber (Isopoda,
      Crustacea) in laboratory-controlled experiments. In the work presented here, the
      daily feeding rate of the central 50% of the control population of
      Porcellioscaber and a correlation between feeding rate and isopod weight were
      set. Values outside these ranges need additional evaluation to increase the
      relevance of test outcomes. We suggest using benchmark values for feeding
      parameters as well as the coefficient of variation (a) to identify animals with
      altered feeding parameters with respect to controls, and (b) to assess the data
      quality in each experiment. 

PMID- 25561845
TI  - Agonistic behaviour in juvenile southern rock lobster, Jasusedwardsii (Decapoda,
      Palinuridae): implications for developing aquaculture.
AB  - The Southern rock lobster, Jasusedwardsii, is a temperate species of spiny
      lobster with established well managed fisheries in Australia and New Zealand. It
      has also been under consideration as a species with aquaculture potential.
      Agonistic behaviour has important consequences under aquaculture conditions that
      encompass direct effects, such as damage or death of protagonists, and indirect
      effects on growth that relate to resource access, principally food and refuge.
      This study aimed to identify and characterize behaviours and to make a
      preliminary investigation of their occurrence under tank culture. Juvenile
      Jasusedwardsii were examined in a flow-through seawater system using a remote
      video camera system. Twenty-nine behaviours were divided into three sub-groups:
      aggressive (11), avoidance (6) and others (12). Aggressive behaviours included
      attacks, pushing, lifting, clasping and carrying an opponent. Avoidance
      behaviours included moving away in a backwards-, forwards- or side-stepping
      motion as well as with more vigorous tail flips. These behaviours were components
      of twelve behavioural groups that described contact, attack and displacement
      between individuals. Activity was crepuscular with two clear peaks, one in the
      morning and the other in the evening. The occurrence of behavioural groups was
      not different between the morning and evening. The frequency of aggressive
      behaviours was not affected by changes made to stocking density or access to
      food. The implications of agonistic behaviours are discussed further in relation
      to developing aquaculture. 

PMID- 25561846
TI  - Multiple parasitic crustacean infestation on belonid fish Strongylurastrongylura.
AB  - Simultaneous multiple infestation of parasitic crustacean species involving a
      cymothoid isopod, Cymothoafrontalis Milne Edward, 1840 and four species of
      copepods such as Lernanthropustylosuri Richiardi, 1880, Caligodeslacinatus
      Kroyer, 1863, Bomolochusbellones Burmeister, 1833 and Dermoergasiluscoleus
      Cressey & Collette, 1970 was frequently noticed on spot-tail needlefish,
      Strongylurastrongylura (Belonidae) captured from the Malabar coast (Kerala,
      India) during the period from April 2011 to March 2012. All the 43 fishes
      (Strongylurastrongylura) collected, were under the hyper-infection with parasitic
      crustaceans; a total of 388 parasitic crustaceans including 57 Cymothoafrontalis,
      252 Lernanthropustylosuri, 31 Caligodeslacinatus, 24 Bomolochusbellones and 32
      Dermoergasiluscoleus were recovered from the host fish. 4 members (9.30%) of host
      fish were under quadruple parasitism, in two different combinations. Seventeen
      (39.53%) host fishes showed triple parasitism and 20 (46.51%) members exhibited
      double parasitism, with four and five parasitic combinations respectively.
      Remaining two (4.65%) fishes were parasitized only by the copepod,
      Lernanthropustylosuri. The infestations by all recovered parasitic crustaceans
      were highly site specific. The damage caused by the parasitic crustaceans was
      also discussed. 

PMID- 25561847
TI  - Susceptibility to an inoculum of infectious hypodermal and haematopoietic
      necrosis virus (IHHNV) in three batches of whiteleg shrimp Litopenaeusvannamei
      (Boone, 1931).
AB  - The present study evaluated the susceptibility of three different batches of
      whiteleg shrimp Litopenaeusvannamei from Mexico to an inoculum of infectious
      hypodermal and haematopoietic necrosis virus (IHHNV). Each of the three shrimp
      batches came from a different hatchery. Because of their origin, it was possible
      that the genetic makeup of these batches was different among each other. The
      three batches tested showed differences in IHHNV susceptibility. Here,
      susceptibility is defined as the capacity of the host to become infected, and it
      can be measured by the infectivity titer. Susceptibility to IHHNV was observed in
      decreasing order in shrimp from batch 1 (hatchery from El Rosario, Sinaloa),
      batch 3 (hatchery from Nayarit) and batch 2 (hatchery from El Walamo, Sinaloa),
      respectively. The largest susceptibility difference between batches was 5012
      times, and that between early and late juveniles from the same batch was 25
      times. These results indicate that within a species, susceptibility to a pathogen
      such as IHHNV can have large differences. Susceptibility to pathogens is an
      important trait to consider before performing studies on pathogenesis. It may
      influence virological parameters such as speed of replication, pathogenicity and
      virus titer. In order to evaluate the potential use of IHHNV as a natural control
      agent against white spot syndrome virus (WSSV), it is necessary to know host
      susceptibility and the kinetics of IHHNV infection. These features can help to
      determine the conditions in which IHHNV could be used as antagonist in a WSSV
      infection. 

PMID- 25561848
TI  - Preliminary survey of a nemertean crab egg predator, Carcinonemertes, on its host
      crab, Callinectesarcuatus (Decapoda, Portunidae) from Golfo de Nicoya, Pacific
      Costa Rica.
AB  - The possible presence of egg predators in brood masses of portunid crabs from
      Pacific Central America has not been studied yet. This survey reports the finding
      of a nemertean crab egg predator on the portunid crab, Callinectesarcuatus, from
      the Golfo de Nicoya, Pacific Costa Rica. Nemerteans were found in the egg masses
      of 26 out of the 74 crabs for a prevalence of 35%. The intensity (mean number of
      worms/ infected crab) was estimated to be 18 with a variance of 1-123
      worms/infected crab. No nemerteans were observed either in the 19
      Callinectesarcuatus from Golfo Dulce (southern Pacific coast) and the 10
      Portunusasper from Herradura-Jaco (central Pacific coast). This nemertean is a
      member of the genus Carcinonemertes, which has been reported from the Caribbean
      coast of Panama. However, the encountered Carcinonemertes sp. is the first
      published finding and report from Costa Rica and Pacific Central America. 

PMID- 25561849
TI  - Review of Gasteruption Latreille (Hymenoptera, Gasteruptiidae) from Iran and
      Turkey, with the description of 15 new species.
AB  - The genus Gasteruption Latreille, 1796 (Hymenoptera: Evanioidea: Gasteruptiidae:
      Gasteruptiinae) from North Iran and Turkey is revised, keyed and fully
      illustrated for the first time. In total 36 species are treated of which 33 are
      recorded from Turkey and 23 from Iran. Fifteen species are new for science:
      Gasteruptionaciculatum van Achterberg, sp. n., Gasteruptionagrenum van
      Achterberg, sp. n., Gasteruptionbrevibasale van Achterberg & Saure, sp. n.,
      Gasteruptioncoriacoxale van Achterberg, sp. n., Gasteruptionflavimarginatum van
      Achterberg, sp. n., Gasteruptionheminitidum van Achterberg, sp. n.,
      Gasteruptionhenseni van Achterberg, sp. n., Gasteruptionischnolaimum van
      Achterberg, sp. n., Gasteruptionnigrapiculatum van Achterberg, sp. n.,
      Gasteruptionpaglianoi van Achterberg & Saure, sp. n., Gasteruptionpseudolaticeps
      van Achterberg, sp. n., Gasteruptionpunctifrons van Achterberg, sp. n.,
      Gasteruptionschmideggeri van Achterberg & Saure, sp. n., Gasteruptionscorteum van
      Achterberg, sp. n. and Gasteruptionsmitorum van Achterberg, sp. n. Twenty-one
      species are reported new for Turkey and 16 species new for Iran. Fifteen new
      synonyms are proposed: Foenusterrestris Tournier, 1877, Gasteruptiontrifossulatum
      Kieffer, 1904, and Gasteruptionignoratum Kieffer, 1912, of Gasteruptioncaucasicum
      (Guerin-Meneville, 1844); Gasteruptiondaisyi Alekseev, 1993, of
      Gasteruptiondolichoderum Schletterer, 1889; Gasteruptionassectatorvar.nitidulum
      Schletterer, 1885, of Gasteruptionfreyi (Tournier, 1877);
      Gasteruptionschossmannae Madl, 1987, of Gasteruptionhastator (Fabricius, 1804);
      Gasteryptionfallaciosum Semenov, 1892, Gasteruptiondubiosum Semenov, 1892 and
      Gasteruptionobsoletum Semenov, 1892, of Gasteruptioninsidiosum Semenov, 1892;
      Gasteryptionschewyrewi Semenov, 1892, of Gasteruptionjaculator (Linnaeus, 1758);
      Gasteruptionfloreum Szepligeti, 1903, of Gasteruptionlugubre Schletterer, 1889;
      Gasteruptiontrichotomma Kieffer, 1904, and Gasteruptionpalaestinum Pic, 1916, of
      Gasteruptionmerceti Kieffer, 1904; Gasteryptionfoveiceps Semenov, 1892, of
      Gasteruptionnigrescens Schletterer, 1885, and Gasteruptionlibanense Pic, 1916, of
      Gasteruptionsyriacum Szepligeti, 1903. Gasteruptionlugubre Schletterer, 1889, is
      recognised as a valid species. Lectotypes are designated for Ichneumonassectator
      Linnaeus, 1758; Ichneumonjaculator Linnaeus, 1758; Foenusterrestris Tournier,
      1877; Foenusfreyi Tournier, 1877; Foenusnigripes Tournier, 1877; Foenusgoberti
      Tournier, 1877; Foenusgranulithorax Tournier, 1877; Foenusminutus Tournier, 1877;
      Foenusborealis Thomson, 1883; Faenusdiversipes Abeille de Perrin, 1879;
      Foenusrugulosus Abeille de Perrin, 1879; Faenusobliteratus Abeille de Perrin,
      1879; Faenusundulatum Abeille de Perrin, 1879; Faenusvariolosus Abeille de
      Perrin, 1879; Gasteruptiondistinguendum Schletterer, 1885; Gasteruptionlaeviceps
      Schletterer, 1885; Gasteruptionthomsonii Schletterer, 1885;
      Gasteruptionfoveolatum Schletterer, 1889; Gasteruptionsowae Schletterer, 1901;
      Gasteruptionfoveolum Szepligeti, 1903; Gasteruptionfloreum Szepligeti, 1903;
      Gasteruptioncaudatum Szepligeti, 1903; Gasteruptionsyriacum Szepligeti, 1903;
      Gasteruptionmerceti Kieffer, 1904 and Gasteruptionignoratum Kieffer, 1912. A
      neotype is designated for Gasteruptiontournieri Schletterer, 1885. 

PMID- 25561850
TI  - Lithobius (Monotarsobius) zhangi sp. n., a new species from Eastern China
      (Chilopoda, Lithobiomorpha, Lithobiidae).
AB  - Lithobius (Monotarsobius) zhangisp. n. (Lithobiomorpha: Lithobiidae), recently
      discovered from Nanshan Park, Yantai City, Shandong Province, and Wuyishan
      County, Nanping City, Fujian Province, from China, is described. Morphologically
      it resembles Lithobius (Monotarsobius) songi Pei, Ma, Shi, Wu, Zhou, 2011 from
      Province Hebei, China, but can be readily distinguished from the latter by
      antennae composed of 15+15-19+19 articles versus 19+19-21+21 articles, terminal
      claw of female gonopods inner tooth broader than the outer vs dorsal and ventral
      tooth about same in size, ventral plectrotaxy 01320, dorsal plectrotaxy 10210 in
      the 14th legs, 01210 and 10200 respectively in Lithobius (Monotarsobius) songi. A
      key to the Lithobius (Monotarsobius) species of China and Korea is presented. 

PMID- 25561851
TI  - The millipede genus Eviulisoma Silvestri, 1910 in Kenya, with descriptions of new
      species (Diplopoda, Polydesmida, Paradoxosomatidae).
AB  - The genus Eviulisoma, the largest among Afrotropical Paradoxosomatidae, currently
      encompasses 36 species or subspecies, including six new from Kenya:
      Eviulisomangaia sp. n., Eviulisomangaiaorum sp. n., Eviulisomataitaorum sp. n.,
      Eviulisomataita sp. n., Eviulisomakirimeri sp. n. and Eviulisomakakamega sp. n.
      In addition, Eviulisomaalluaudi Brolemann, 1920 and Eviulisomasilvestre (Carl,
      1909) are recorded for the first time beyond their type localities in Kenya and
      Tanzania, respectively, based on new material from Kenya. A key is given to all
      ten species of the genus presently reported from Kenya. 

PMID- 25561852
TI  - A new species of Halicyclops (Copepoda, Cyclopoida, Cyclopidae) from a lagoon
      system of the Caribbean coast of Colombia.
AB  - Plankton samples obtained from the lagoon system Laguna Navio Quebrado, in
      northern Colombia, yielded male and female specimens of an undescribed cyclopoid
      copepod of the genus Halicyclops. The new species belongs to the highly diverse
      and widely distributed thermophilus-complex. It closely resembles
      Halicyclopsclarkei Herbst, 1982 from Louisiana and Halicyclopsbowmani Rocha &
      Iliffe, 1993 from Bermuda. These species share the same armature of P1-P4EXP3,
      with a 3443 spine formula and the terminal antennary segment with 5 setae.
      However, Halicyclopsgaviriai sp. n. can be separated from both Halicyclopsclarkei
      and Halicyclopsbowmani by the morphology of the anal pseudoperculum, the
      proportions of the fourth antennulary segment, the length of the inner basipodal
      spine of P1, the P1EXP/inner basipodal spine inner length ratio and the
      length/width ratio of the caudal rami. This is the third species of Halicyclops
      recorded from Colombia and the first one described from this country. With the
      addition of Halicyclopsgaviriai sp. n., the number of species of Halicyclops
      known from the Neotropics increases to 19. The regional diversity of the genus is
      probably underestimated. 

PMID- 25561853
TI  - Molecular and morphological differentiation between Aphis gossypii Glover
      (Hemiptera, Aphididae) and related species, with particular reference to the
      North American Midwest.
AB  - The cotton aphid, Aphis gossypii, is one of the most biologically diverse species
      of aphids; a polyphagous species in a family where most are host specialists. It
      is economically important and belongs to a group of closely related species that
      has challenged aphid taxonomy. The research presented here seeks to clarify the
      taxonomic relationships and status of species within the Aphid gossypii group in
      the North American Midwest. Sequences of the mitochondrial cytochrome oxidase 1
      (COI), nuclear elongation factor 1-alpha (EF1-alpha), and nuclear sodium channel
      para-type (SCP) genes were used to differentiate between Aphid gossypii and
      related species. Aphis monardae, previously synonymised with Aphid gossypii, is
      re-established as a valid species. Phylogenetic analyses support the close
      relationship of members of the Aphid gossypii group native to North America
      (Aphid forbesi, Aphid monardae, Aphid oestlundi, Aphid rubifolii, and Aphid
      rubicola), Europe (Aphid nasturtii, Aphid urticata and Aphid sedi), and Asia
      (Aphid agrimoniae, Aphid clerodendri, Aphid glycines, Aphid gossypii, Aphid
      hypericiphaga, Aphid ichigicola, Aphid ichigo, Aphid sanguisorbicola, Aphid
      sumire and Aphid taraxicicola). The North American species most closely related
      to Aphid gossypii are Aphid monardae and Aphid oestlundi. The cosmopolitan Aphid
      gossypii and Aphid sedi identified in the USA are genetically very similar using
      COI and EF1-alpha sequences, but the SCP gene shows greater genetic distance
      between them. We present a discussion of the biological and morphological
      differentiation of these species.

PMID- 25561854
TI  - Revision of the plant bug genus Xenocylapidius (Hemiptera, Heteroptera, Miridae,
      Cylapinae), with descriptions of five new species from Australia and New
      Caledonia.
AB  - The genus Xenocylapidius Gorczyca, 1997 is revised. Five new species:
      Xenocylapidiusacutipennis sp. n., Xenocylapidiusater sp. n.,
      Xenocylapidiusbimaculatus sp. n., Xenocylapidiusgemellus sp. n., and
      Xenocylapidiusrolandi sp. n. are described from Australia and New Caledonia.
      Illustrations of the male genitalia, color photographs of dorsal and lateral
      views of the adults of all species, and key to species of the genus
      Xenocylapidius are provided. 

PMID- 25561855
TI  - Diversity, distribution and biology of Romanian flat-footed flies (Diptera,
      Opetiidae and Platypezidae) with taxonomic notes on Callomyiasaibhira Chandler.
AB  - Altogether 18 species of the families Opetiidae and Platypezidae are reported
      from Romania, based on newly studied material and previously published records.
      The following three species are recorded from Romania for the first time:
      Agathomyiavernalis Shatalkin, 1981, Callomyiasaibhira Chandler, 1976, and
      Lindneromyiahungarica Chandler, 2001. The presented differential diagnosis and a
      detailed redescription of body and genitalia of the male of Callomyiasaibhira are
      based on one specimen which is the first male found in Europe. Information about
      distribution and biology of all 18 Romanian species is provided as well as
      photographs of selected important species. Finally, a new checklist of all
      Romanian species is given. 

PMID- 25561856
TI  - Coleophoranepetellae Baldizzone & Nel, a new species of the C.lixella group
      (Lepidoptera, Coleophoridae) from France and Italy.
AB  - Coleophoranepetellae Baldizzone & Nel, sp. n. is described from the southern Alps
      (Italy and France). It belongs to the Coleophoralixella species group. Its host
      plants are Nepetanepetella L. (Lamiaceae) and an unidentified Poaceae. The fifth
      instar larva, its case, the adult habitus, and genitalia are illustrated. The
      species is compared to Coleophoranevadella Baldizzone, 1985, here newly confirmed
      from France and whose larvae feed on Nepetalatifolia DC. in the Eastern Pyrenees.
      DNA barcodes are shown to be distinct and congruent with morphological
      differences among species of the lixella group. Barcodes revealed that
      Coleophoratricolor Walsingham, 1889, formerly known only from Great Britain, is
      also present in France and Greece. 

PMID- 25561857
TI  - Acariform mites (Acariformes) - permanent symbionts of Hapalomysdelacouri Thomas
      (Rodentia, Muridae) in Vietnam.
AB  - Two new species of parasitic acariform mites (Acariformes) are described from the
      Delacour's marmoset rat Hapalomysdelacouri Thomas (Rodentia: Muridae) in Vietnam:
      Afrolistrophorus (Afrolistrophorus) hapalomyssp. n. (Listrophoridae) and
      Radfordia (Radfordia) mirabilissp. n. (Myobiidae). Based on morphological
      evidences, we show that species of both mite genera associated with Hapalomys
      Blyth do not demonstrate clear phylogenetic links with respective congeners from
      rodents of the closest genus Chiropodomys Peters (Rodentia: Muridae). 

PMID- 25561858
TI  - A survey of linyphiid spiders from Xishuangbanna, Yunnan Province, China
      (Araneae, Linyphiidae).
AB  - Eight new genera and 30 new species are described: Cirrosus gen. n. (type species
      Cirrosusatrocaudatus sp. n. (??)), Conglin gen. n. (type species
      Conglinpersonatus sp. n. (?)), Curtimeticus gen. n. (type species
      Curtimeticusnebulosus sp. n. (?)), Gladiata gen. n. (type species Gladiatafengli
      sp. n. (?)), Glebala gen. n. (type species Glebalaaspera sp. n. (?)), Glomerosus
      gen. n. (type species Glomerosuslateralis sp. n. (?)), Smerasia gen. n. (type
      species Smerasiaobscurus sp. n. (??)), Vittatus gen. n. (type species
      Vittatusfencha sp. n. (??)); Batuetacuspidata sp. n. (??), Capsulialaciniosa sp.
      n. (?), Dactylopisthesseparatus sp. n. (?), Gongylidiellumbracteatum sp. n. (?),
      Houshenzinusxiaolongha sp. n. (??), Laogonebai sp. n. (?), Laogonelunata sp. n.
      (??), Marobulbosus sp. n. (?), Nasoonariacircinata sp. n. (??), Nerienecircifolia
      sp. n. (??), Oedothoraxbiantu sp. n. (?), Oilinyphiahengji sp. n. (??),
      Paikinianafurcata sp. n. (??), Parameionetabishou sp. n. (??),
      Parameionetamultifida sp. n. (??), Parameionetatricolorata sp. n. (??),
      Tapinopaundata sp. n. (?), Theoabidentata sp. n. (??), Theoavesica sp. n. (??),
      Vittatusbian sp. n. (??), Vittatuslatus sp. n. (??), Vittatuspan sp. n. (??). The
      male of Kaestneriabicultrata Chen & Yin, 2000 and the females of
      Asiagoneperforata Tanasevitch, 2014 and Batuetasimilis Wunderlich & Song, 1995
      are described for the first time; photos of Bathyphantesparacymbialis
      Tanasevitch, 2014 are provided. 

PMID- 25561859
TI  - A synopsis of the genus Ethmia Hubner in Costa Rica: biology, distribution, and
      description of 22 new species (Lepidoptera, Gelechioidea, Depressariidae,
      Ethmiinae), with emphasis on the 42 species known from Area de Conservacion
      Guanacaste.
AB  - We discuss 45 Costa Rican species of Ethmia Hubner, 1819, including 23 previously
      described: Ethmiadelliella (Fernald), Ethmiabittenella (Busck), Ethmiafestiva
      Busck, Ethmiascythropa Walsingham, Ethmiaperpulchra Walsingham, Ethmiaterpnota
      Walsingham, Ethmiaelutella Busck, Ethmiajanzeni Powell, Ethmiaungulatella Busck,
      Ethmiaexornata (Zeller), Ethmiaphylacis Walsingham, Ethmiamnesicosma Meyrick,
      Ethmiachemsaki Powell, Ethmiabaliostola Walsingham, Ethmiaduckworthi Powell,
      Ethmiasandra Powell, Ethmianigritaenia Powell, Ethmiacatapeltica Meyrick,
      Ethmialichyi Powell, Ethmiatransversella Busck, Ethmiasimilatella Busck,
      Ethmiahammella Busck, Ethmialinda Busck, and 22 new species: Ethmiablaineorum,
      Ethmiamillerorum, Ethmiadianemillerae, Ethmiaadrianforsythi,
      Ethmiastephenrumseyi, Ethmiaberndkerni, Ethmiadimauraorum, Ethmiabillalleni,
      Ethmiaehakernae, Ethmiahelenmillerae, Ethmiajohnpringlei, Ethmialaphamorum,
      Ethmiapetersterlingi, Ethmialesliesaulae, Ethmiaturnerorum, Ethmianormgershenzi,
      Ethmianicholsonorum, Ethmiahendersonorum, Ethmiarandyjonesi, Ethmiarandycurtisi,
      Ethmiamiriamschulmanae and Ethmiatilneyorum. We illustrate all species and their
      male and female genitalia, along with distribution maps of Costa Rican
      localities. Immature stages are illustrated for 11 species, and food plants are
      listed when known. Gesneriaceae is added as a new food plant family record for
      Ethmia. CO1 nucleotide sequences ("DNA barcodes") were obtained for 41 of the
      species. 

PMID- 25561860
TI  - Is mapping borders between pharmacology and toxicology a necessity?

PMID- 25561861
TI  - The experiences of implementing generic medicine policy in eight countries: A
      review and recommendations for a successful promotion of generic medicine use.
AB  - Generic medicines are clinically interchangeable with original brand medicines
      and have the same quality, efficacy and safety profiles. They are, nevertheless,
      much cheaper in price. Thus, while providing the same therapeutic outcomes,
      generic medicines lead to substantial savings for healthcare systems. Therefore,
      the quality use of generic medicines is promoted in many countries. In this
      paper, we reviewed the role of generic medicines in healthcare systems and the
      experiences of promoting the use of generic medicines in eight selected
      countries, namely the United States (US), the United Kingdom (UK), Sweden,
      Finland, Australia, Japan, Malaysia and Thailand. The review showed that there
      are different main policies adopted to promote generic medicines such as generic
      substitution in the US, generic prescribing in the UK and mandatory generic
      substitution in Sweden and Finland. To effectively and successfully implement the
      main policy, different complementary policies and initiatives were necessarily
      introduced. Barriers to generic medicine use varied between countries from
      negative perceptions about generic medicines to lack of a coherent generic
      medicine policy, while facilitators included availability of information about
      generic medicines to both healthcare professionals and patients, brand
      interchangeability guidelines, regulations that support generic substitution by
      pharmacists, and incentives to both healthcare professionals and patients. 

PMID- 25561862
TI  - Low density lipoprotein bionanoparticles: From cholesterol transport to delivery
      of anti-cancer drugs.
AB  - In this review article, we highlight the importance of low-density lipoprotein
      (LDL) and its implications in the field of drug delivery to cancer cells. LDL is
      naturally occurring bionanoparticles (BNP) with a size of 18-25 nm. These BNPs
      specifically transport cholesterol to cells expressing the LDL receptors (LDLRs).
      Several tumors overexpress LDLRs, presumably to provide cholesterol for
      sustaining a high rate of membrane synthesis. LDL BNPs are biocompatible and
      biodegradable, favorably bind hydrophobic and amphiphilic drugs, are taken up by
      a receptor-mediated mechanism, have a half-life of 2-4 days, and can be rerouted.
      Drugs can be loaded onto LDL BNPs by surface loading, core loading, and
      apoprotein interaction. LDL may be used as a drug carrier for treatment of
      atherosclerosis, cancer, and in photodynamic therapies. 

PMID- 25561863
TI  - The impact of clinical pharmacist and ID intervention in rationalization of
      antimicrobial use.
AB  - WHAT IS KNOWN AND OBJECTIVE: There is little research on the impact of
      implementing and monitoring antimicrobial policy in Saudi hospitals. The purpose
      of this study is to measure the impact of the clinical pharmacist (CP) and
      infectious disease consultant (ID) interventions on the use of three
      antimicrobials (caspofungin, imipenem, meropenem) in hospitalized patients in the
      King Abdullah Medical City hospital. METHODS: The study was carried out in the
      King Abdullah Medical City, in Mekkah, Saudi Arabia. The hospital is a tertiary
      center that provides CCU, CSICU, Cardiac, Hematology, ICU, Medical, Neuroscience,
      Oncology, and specialized surgery services. The use of three antimicrobials
      (caspofungin, imipenem, meropenem) was reviewed by the clinical pharmacist for
      four periods, pre and post implementation of policy. Relevant data were collected
      in four periods. In the first period, before policy implementation, data were
      collected retrospectively to be used as baseline status reference, and in the
      three remaining periods that followed data were collected prospectively, and
      compared to baseline data, to evaluate the role of clinical pharmacist and ID
      interventions in optimizing antimicrobial therapy. RESULTS AND DISCUSSION:
      Caspofungin duration of therapy was not affected significantly by the
      intervention. Statistically significant reduction in antimicrobial therapy
      duration was observed in imipenem (37%) and meropenem (37%) from baseline, which
      indicate a better control on antimicrobial use and reduction in antimicrobial
      resistance. WHAT IS NEW AND CONCLUSION: The impact of the clinical pharmacist and
      ID interventions, in reducing antimicrobial therapy duration using imipenem and
      meropenem, is clear from the result presented above. However, lack of restriction
      and follow up in the antimicrobial policy in case of negative culture makes
      antimicrobial use uncontrollable in these cases. Establishing good and accepted
      policy may help reduce consumption and total cost of therapy.

PMID- 25561865
TI  - Pharmacists' and physicians' perception and exposure to drug promotion: A Saudi
      study.
AB  - INTRODUCTION: Drug promotion has to contribute to a more rational use of drugs.
      Concerns arise if promotion negatively influences prescribing/dispensing pattern.
      It is warranted to assess exposure and attitudes to, and acceptance of, drug
      promotion among pharmacists and physicians. METHODOLOGY: Adopting a randomized,
      multiple site and cross-sectional survey study, questionnaires (n = 250) were
      completed by physicians and pharmacists to investigate the exposure, acceptance
      or skepticism of Saudi physicians/pharmacists to drug promotion as well as their
      perception of the appropriateness of gifts and to check if they had any
      teaching/training about dealing with medical representatives (MRs) and Pharma
      promotion. RESULTS: Significantly more pharmacists than physicians (32% vs. 23%;
      p < 0.05) reported being taught or educated about the ethics of drug promotion.
      The experience level was significantly associated with the teaching or training
      that the physicians and pharmacists received. Conference registration fees and
      drug samples were the most appropriate promotional gift for the physicians (67%
      and 66%, respectively; p < 0.01) whereas for pharmacists, the drug sample was
      considered the most suitable donation (79%). More pharmacists perceived drug
      companies as a useful way to gain knowledge about drugs than physicians (75% vs.
      65%; p < 0.01). A higher proportion of both groups were accepting drug promotion
      than those skeptical about it. CONCLUSION: The majority of physicians or
      pharmacists participating in this study have received gifts from pharmaceutical
      companies. The drug samples and printed educational materials are the most widely
      accepted gifts. Recent graduates and those with few years of experience had
      higher teaching/training than experienced physicians and pharmacists in
      pharmaceutical promotion ethics and tactics to deal with MRs. On the other hand,
      experienced healthcare team were more approached and targeted by pharmaceutical
      companies and MRs. It is highly recommended to implement courses/discussion
      groups on the ethical interaction between healthcare professionals and
      pharmaceutical companies in the curriculum of both pharmacy and medicine.
      Updating the physicians and pharmacists after graduation, as part of continued
      medical/pharmacy education, will eventually improve the healthcare professionals'
      capability to act to the patients' welfare.

PMID- 25561866
TI  - Physicians' and patients' valuation of pharmaceutical care implementation in
      Poznan (Poland) community pharmacies.
AB  - Implementation of pharmaceutical care (PC) in Poland is of great importance to
      patients, who, on the one hand, often follow complex pharmacological treatment
      regimens recommended by several physicians of different specialties, and, on the
      other, take up the decision on self-treatment due to availability of OTC
      medications. The aim of the present study was to assess the opinion of both
      patients and physicians about implementation of PC service in Polish community
      pharmacies. A cross sectional study was carried out from September 2009 to
      September 2010 by a pharmacist (author of the study) on the basis of an anonymous
      questionnaire, where demand of physicians (n = 104) and patients (n = 202) for
      implementation of PC in a community pharmacy was assessed. The study was planned
      to determine the relationship between implementation of PC, cost and time of this
      service and patients' and physicians' socio-economic information. Responding
      patients (85.64%) and physicians (76.92%) unanimously confirmed the need for
      implementation of PC. Most people convinced of the service implementation were
      88.89% of physicians under the age of 35 and all the respondents were over 65
      years of age (p = 0.027), just as 93.33% with service lesser than 5 years and
      73.68% of respondents working a maximum of 20 years (p = 0.023). Mainly according
      to 90.00% of physicians with specialty in internal medicine and 92.59% of
      physicians of the group "Others" (p = 0.012), PC should be implemented in
      pharmacies. Women more frequently than men reckoned that appointments with a
      pharmacist should last up to 15 min (p = 0.012). According to 77.78% of the
      youngest physicians and 83.33% of the oldest ones, appointments should last from
      5 to 15 min (p = 0.049), and a similar opinion was shared by 80.77% of physicians
      without specialty and 77.78% of physicians of the group "Others" (p = 0.0009).
      According to patients, the mean cost of the visit should be USD 7. Physicians
      most often assessed the mean cost of the appointment at USD 14. This study
      provides new data about implementation of PC in Poland. The increased patients'
      and physicians' willingness to benefit from this service provides pharmacists
      with opportunities to develop PC in community pharmacies. 

PMID- 25561864
TI  - Assessment of legibility and completeness of handwritten and electronic
      prescriptions.
AB  - OBJECTIVES: To assess the legibility and completeness of handwritten
      prescriptions and compare with electronic prescription system for medication
      errors. DESIGN: Prospective study. SETTING: King Khalid University Hospital
      (KKUH), Riyadh, Saudi Arabia. SUBJECTS AND METHODS: Handwritten prescriptions
      were received from clinical units of Medicine Outpatient Department (MOPD),
      Primary Care Clinic (PCC) and Surgery Outpatient Department (SOPD) whereas
      electronic prescriptions were collected from the pediatric ward. The handwritten
      prescription was assessed for completeness by the checklist designed according to
      the hospital prescription and evaluated for legibility by two pharmacists. The
      comparison between handwritten and electronic prescription errors was evaluated
      based on the validated checklist adopted from previous studies. MAIN OUTCOME
      MEASURES: Legibility and completeness of prescriptions. RESULTS: 398
      prescriptions (199 handwritten and 199 e-prescriptions) were assessed. About 71
      (35.7%) of handwritten and 5 (2.5%) of electronic prescription errors were
      identified. A significant statistical difference (P < 0.001) was observed between
      handwritten and e-prescriptions in omitted dose and omitted route of
      administration category of error distribution. The rate of completeness in
      patient identification in handwritten prescriptions was 80.97% in MOPD, 76.36% in
      PCC and 85.93% in SOPD clinic units. Assessment of medication prescription
      completeness was 91.48% in MOPD, 88.48% in PCC, and 89.28% in SOPD. CONCLUSIONS:
      This study revealed a high incidence of prescribing errors in handwritten
      prescriptions. The use of e-prescription system showed a significant decline in
      the incidence of errors. The legibility of handwritten prescriptions was
      relatively good whereas the level of completeness was very low.

PMID- 25561867
TI  - An influence of adrenaline (1:80,000) containing local anesthesia (2% Xylocaine)
      on glycemic level of patients undergoing tooth extraction in Riyadh.
AB  - OBJECTIVE: Aim is to compare the glycemic level among patients before, and after
      local anesthesia containing adrenaline 1:80,000 among patients who need dental
      extraction. MATERIALS AND METHODS: 60 patients were randomly selected including
      30 healthy and 30 with a diabetes history for this study in Riyadh city. First
      the blood glucose level was measured before administering local anesthesia
      containing adrenaline after taking their history with glucocheck according to
      instructions, then blood Sugar level was recorded after administering local
      anesthesia containing adrenaline 1:80,000 concentrations. Blood sugar level was
      also checked 5 min after the tooth extraction procedure. RESULTS: There were no
      significant results found after the administration of local anesthesia containing
      adrenaline in both healthy and diabetic patients (p > 0.05). However, change of
      significance (p < 0.05) was noticed in diabetic patients who had not taken their
      hypoglycemic medication; there was a rise in their blood glucose level after
      extraction. CONCLUSION: The study concluded no significant effect on the glycemic
      level of patients after the administration of local anesthesia containing
      adrenaline 1:80,000 in healthy and diabetic patients whether hypoglycemic
      medication was taken or not but a rise in blood sugar level was found among
      diabetic patients who did not take their hypoglycemic medications undergoing
      tooth extraction.

PMID- 25561868
TI  - Public attitude and justification to purchase antibiotics in the Eastern region
      Al Ahsa of Saudi Arabia.
AB  - Use of non-prescription antibiotics can portend danger and predispose the
      populace to changes in bacterial resistance pattern. The aims of this study were
      to (a) evaluate the knowledge and attitudes of residents of Al-Ahsa community,
      Saudi Arabia on the use of non-prescribed antibiotics. (b) To identify possible
      predictors (if any) for self-medication within the community. A cross-sectional
      survey study, using self-administered questionnaire was conducted in two
      sections; demographics and self-medication attitude (in form of self-antibiotic
      use). Questions contained the following outcomes; for demographics; gender, age,
      education level and common disease within the community. Whereas the second part
      evaluated sources of information, knowledge of antibiotics, frequency/duration of
      use, underlined illness in which drug use was employed, names of antibiotics used
      and awareness of adverse effects of antibiotics. Results revealed that the adult
      population in the 18-40 year age range constituted about 82.5% of the
      respondents. Also 18-29 age group made of 60.5% of the respondents and that 56.8%
      the respondents are university graduates. Cold (18.8%) and sore throat (13.0%)
      were the diseases commonly found among the community that drove them to using non
      prescribed antibiotics. About 337 (72.8%) of the respondent mention the use of
      antibiotics to treat the illness, and 21 (4.5%) were aiming to prevent the
      illness. While, 19.4% of the respondents admitted to taking non-prescribed
      antibiotics for both prevention and treatment of illness. 43.6% of the
      respondents disclosed that they are not aware of the dangers of using non
      prescribed antibiotics. In conclusion the use of non-prescribed antibiotics in
      this community is evident, as a significant number use them from previous
      experience for prevention and treatment of illness. Therefore introduction of
      rational use of drugs will help in limiting the attendant development of
      bacterial resistance. 

PMID- 25561869
TI  - Formulation and evaluation of new long acting metoprolol tartrate ophthalmic
      gels.
AB  - The rationale of the present work is to formulate and evaluate metoprolol
      tartrate (MT), which is a beta-1 selective adrenergic blocking agent in a new
      ocular gel delivery system; this is our way and method to increase its contact to
      the cornea, giving a longer time of drug contact to the eye and slow possible
      release from the preparation. Metoprolol tartrate is chosen as a candidate for
      gel formulation because although it has been available for a few years as
      ophthalmic solutions, it has not been marketed as an ocular gel yet. Two
      polymers; Carbopol 934 and Pluronic F127 (PF127) were used in two different
      concentrations in this study. Metoprolol tartrate was used in two concentrations,
      0.5% and 1% (w/w). All formulations were exposed to visual examinations, pH
      measurement, in vitro release, rheological study and differential scanning
      calorimetry (DSC). Results showed that all formulations were clear, showed pH
      within the acceptable range suitable to be administered in the eye, and exhibited
      pseudoplastic flow behavior. DSC results concluded that, MT was compatible with
      different polymers used. In vitro release results showed that the release rate of
      metoprolol tartrate from gel preparations decreased as an inverse function of
      polymer concentration, and the release rate of the drug increased as the initial
      concentration increased. Intra-ocular pressure (IOP) measurements of rabbit's eye
      treated with 1% (w/w) metoprolol tartrate in gel formulations with different
      concentrations of the polymer were determined. Carbopol 934 gel formulations
      showed that this polymer extended the duration of pressure reducing effect of MT
      to more than 5hr when compared with Pluronic F127 gel formulations. The area
      above the curve (AAC), maximum response, time of maximum response (t max), and
      the duration of the drug action were also calculated. 

PMID- 25561870
TI  - Modulation of CYP2D6 and CYP3A4 metabolic activities by Ferula asafetida resin.
AB  - Present study investigated the potential effects of Ferula asafetida resin on
      metabolic activities of human drug metabolizing enzymes: CYP2D6 and CYP3A4.
      Dextromethorphan (DEX) was used as a marker to assess metabolic activities of
      these enzymes, based on its CYP2D6 and CYP3A4 mediated metabolism to dextrorphan
      (DOR) and 3-methoxymorphinan (3-MM), respectively. In vitro study was conducted
      by incubating DEX with human liver microsomes and NADPH in the presence or
      absence of Asafetida alcoholic extract. For clinical study, healthy human
      volunteers received a single dose of DEX alone (phase-I) and repeated the same
      dose after a washout period and four-day Asafetida treatment (phase-II).
      Asafetida showed a concentration dependent inhibition on DOR formation (in vitro)
      and a 33% increase in DEX/DOR urinary metabolic ratio in clinical study. For
      CYP3A4, formation of 3-MM in microsomes was increased at low Asafetida
      concentrations (10, 25 and 50 MUg/ml) but slightly inhibited at the concentration
      of 100 MUg/ml. On the other hand, in vivo observations revealed that Asafetida
      significantly increased DEX/3-MM urinary metabolic ratio. The findings of this
      study suggest that Asafetida may have a significant effect on CYP3A4 metabolic
      activity. Therefore, using Ferula asafetida with CYP3A4 drug substrates should be
      cautioned especially those with narrow therapeutic index such as cyclosporine,
      tacrolimus and carbamazepine. 

PMID- 25561871
TI  - Design and evaluation of gastroretentive levofloxacin floating mini-tablets-in
      capsule system for eradication of Helicobacter pylori.
AB  - Gastroretentive levofloxacin (LVF) floating mini-tablets for the eradication of
      Helicobacter pylori (H. pylori) were prepared using the matrix forming polymer
      hydroxypropyl methylcellulose (HPMC K100M), alone or with Carbopol 940P in
      different ratios by wet granulation technique. Buoyancy of mini-tablets was
      achieved by an addition of an effervescent mixture consisting of sodium
      bicarbonate and anhydrous citric acid to some formulations. The prepared mini
      tablets were evaluated for weight variation, thickness, friability, hardness,
      drug content, in vitro buoyancy, water uptake and in vitro release. The optimized
      formula was subjected to further studies: FT-IR, DSC analysis and in vivo
      examination in healthy volunteers. The prepared mini-tablets exhibited
      satisfactory physicochemical characteristics. Incorporation of gas-generating
      agent improved the floating parameters. HPMC K100M mini-tablet formulation (F1)
      offered the best controlled drug release (>8 h) along with floating lag time <1 s
      and total floating time >24 h. The obtained DSC thermograms and FT-IR charts
      indicated that there is no positive evidence for the interaction between LVF and
      ingredients of the optimized formula. The in vivo test confirmed the success of
      the optimized formula F1 in being retained in the stomach of the volunteers for
      more than 4 h. LVF floating mini-tablets based on HPMC K100M is a promising
      formulation for eradication of H. pylori. 

PMID- 25561872
TI  - Role of medium-chain fatty acids in the emulsification mechanistics of self-micro
      emulsifying lipid formulations.
AB  - PURPOSE: The objective of the present study was to design and develop stable o/w
      microemulsions comprising Miglyol 812, Imwitor 988 and Tagat TO as a non ionic
      surfactant. This was based on particle size measurements and phase behavior
      studies. The empirical role of incorporating medium-chain mono/di-glycerides in
      the lipid matrix in the mechanistic processes of emulsification was also
      established in various simulating physiological conditions. METHODS: The
      efficiency of self-emulsification was evaluated under conditions of varying key
      compositions in the lipid mixtures; oil, cosurfactant and surfactant. Droplet
      diameter was measured using laser diffraction and light scattering techniques.
      Equilibrium phase studies were performed and phase boundaries were determined for
      the lipid-water systems. RESULTS: Microemulsion systems were produced from blends
      of Miglyol 812, Imwitor 988 and Tagat TO. An optimized formulation consisted of
      {Miglyol 812/Imwitor 988} and Tagat TO spontaneously self-emulsified in water
      producing dispersions with droplet diameters of ~50 nm. Phase equilibrium
      diagrams have revealed significant enhancement in the water-solubilized region
      (L2) without any presence of liquid crystalline materials. CONCLUSIONS: Potential
      SMEDDS formulations for the bioavailability enhancement of poorly water-soluble
      compounds were developed by mixing blends of {Miglyol 812/Imwitor 988} and Tagat
      TO as a non-ionic surfactant. 'Diffusion and stranding' appears to be the
      dominant mechanism of emulsification.

PMID- 25561873
TI  - Calcipotriol delivery into the skin as emulgel for effective permeation.
AB  - The objective of this work is to formulate and evaluate an emulgel containing
      calcipotriol for treatment of psoriasis. Emulgels have emerged as a promising
      drug delivery system for the delivery of hydrophobic drugs. Isopropyl alcohol and
      polyethylene glycol have been employed as permeation enhancers. Formulation chart
      is made with seven formulations, evaluated for physical parameters, drug content,
      viscosity, thixotropy, spreadability, extrudability, mucoadhesion, diffusion
      studies, skin irritation test along with short term stability studies. Carbopolis
      is reported to have a direct influence on appearance and viscosity of final
      formulation. The photomicroscopic evaluations showed the presence of spherical
      globules in size range of 10-15 MUm. Rheograms revealed that all the formulations
      exhibited pseudoplastic flow. Optimized formulation (F6) had shown 86.42 +/- 2.0%
      drug release at the end of 8 h study. The release rate through dialysis membrane
      and rat skin is higher when compared to commercial calcipotriol ointment. Hence
      it is concluded that calcipotriol can be delivered topically with enhanced
      penetration properties when formulated as emulgel. 

PMID- 25561874
TI  - Clinical pharmacists: Bridging the gap between patients and physicians.
AB  - The clinical pharmacy has spread out drastically in terms of its professional
      services throughout the past few years. The clinical pharmacist become a crucial
      element of healthcare team and promotes patient care by interacting with
      physician and patient. The aim of this paper is to highlight the role of clinical
      pharmacists in various departments. It concludes that the features of
      interactions occurring between clinical pharmacists and physicians influence the
      teamwork between pharmacists and physicians and provide better patient care. 

PMID- 25561875
TI  - Biological aspect of various global health issues.

PMID- 25561877
TI  - Does alteration in biodiversity really affect disease outcome? - A debate is
      brewing.
AB  - How changes in biodiversity alter the transmission of infectious diseases is
      presently under debate. Epidemiologists and ecologists have put a lot of effort
      to understand the mechanism behind biodiversity-disease relationship. Two
      important mechanisms, i.e. dilution and amplification theories have in some
      manner made it clear that biodiversity and disease outcome have an intimate
      relationship. The dilution effect theory seems to answer some overarching
      questions, but paucity of information about many disease systems is a real
      obstacle for its acceptance. Also, there is hardly any agreement on host
      population threshold and critical community size vis-a-vis wild life diseases. We
      suggest a multidimensional approach whereby the same disease system needs to be
      studied in different ecological zones and then the effect of biodiversity on
      disease outcome needs to be ascertained. Nonetheless, caution is to be taken
      while jumping to any conclusion as biodiversity-disease relationship is a
      multifactorial process. 

PMID- 25561876
TI  - Alzheimer's disease and type 2 diabetes via chronic inflammatory mechanisms.
AB  - Recent evidence has indicated that type 2 diabetes mellitus (T2DM) increases the
      risk of developing Alzheimer's disease (AD). Therefore, it is crucial to
      investigate the potential common processes that could explain this relation
      between AD and T2DM. In the recent decades, an abundance of evidence has emerged
      demonstrating that chronic inflammatory processes may be the major factors
      contributing to the development and progression of T2DM and AD. In this article,
      we have discussed the molecular underpinnings of inflammatory process that
      contribute to the pathogenesis of T2DM and AD and how they are linked to these
      two diseases. In depth understanding of the inflammatory mechanisms through which
      AD and T2DM are associated to each other may help the researchers to develop
      novel and more effective strategies to treat together AD and T2DM. Several
      treatment options have been identified which spurn the inflammatory processes and
      discourage the production of inflammatory mediators, thereby preventing or
      slowing down the onset of T2DM and AD. 

PMID- 25561878
TI  - An overview on the correlation of neurological disorders with cardiovascular
      disease.
AB  - Neurological disorders (NDs) are one of the leading causes of death especially in
      the developed countries. Among those NDs, Alzheimer's disease (AD) and Parkinson
      disease (PD) are heading the table. There have been several reports in the
      scientific literatures which suggest the linkage between cardiovascular disorders
      (CVDs) and NDs. In the present communication, we have tried to compile NDs (AD
      and PD) association with CVDs reported in the literature. Based on the available
      scientific literature, we believe that further comprehensive study needs to be
      done to elucidate the molecular linking points associated with the above
      mentioned disorders. 

PMID- 25561879
TI  - Clinical biomarkers in sickle cell disease.
AB  - Sickle cell disease (SCD) is a hereditary blood disorder caused by a single gene.
      Various blood and urine biomarkers have been identified in SCD which are
      associated with laboratory and medical history. Biomarkers have been proven
      helpful in identifying different interconnected disease-causing mechanisms of
      SCD, including hypercoagulability, hemolysis, inflammation, oxidative stress,
      vasculopathy, reperfusion injury and reduced vasodilatory responses in
      endothelium, to name just a few. However, there exists a need to establish a
      panel of validated blood and urine biomarkers in SCD. This paper reviews the
      current contribution of biochemical markers associated with clinical
      manifestation and identification of sub-phenotypes in SCD. 

PMID- 25561880
TI  - Reduction of post-prandial hyperglycemia by mulberry tea in type-2 diabetes
      patients.
AB  - AIM: The dietary contents have a very important role in the management of
      metabolic syndrome along with type 2 diabetes mellitus (T2DM). Indian diet
      contains a large amount of carbohydrates that set off unpredictable blood sugar
      fluctuations and leads to increased risk of diabetic complications. The aim of
      the present study was to identify the effect of mulberry tea in the reduction of
      abnormally high postprandial blood glucose (PPG) levels in T2DM patients.
      METHODS: The study design was follow-up T2DM, 20 diabetic patients were given
      plain tea (control) and 28 diabetic patients were given mulberry tea (test
      subject) to measure the effect of mulberry tea on fasting blood glucose and PPG
      levels. Fasting blood glucose samples were collected after a standard breakfast.
      The PPG levels were recorded after the consumption of 70 ml tea along with 1
      teaspoon of sugar after 90 min in all 48 patients. RESULTS: Fasting blood glucose
      levels in control and test group samples were found to be 178.55 +/- 35.61 and
      153.50 +/- 48.10, respectively. After the consumption of plain tea and mulberry
      tea, the PPG values were recorded as 287.20 +/- 56.37 and 210.21 +/- 58.73,
      respectively. A highly significant (p < 0.001) change in the PPG level was
      observed in response to mulberry tea in all the test patients compared with
      control. Moreover, the effect size was also found to be very large (1.31).
      CONCLUSION: Mulberry tea suppresses postprandial rise of blood glucose levels
      after 90 min of its consumption.

PMID- 25561881
TI  - Risk factors for acquisition of extended spectrum beta lactamase producing
      Escherichia coli and Klebsiella pneumoniae in North-Indian hospitals.
AB  - Multidrug resistance and production of extended spectrum beta-lactamases (ESBLs)
      by enteric gram negative rods in hospitals and community continue to be a matter
      of scientific concern. This retrospective study was executed to assess the
      prevalence of ESBL-producing Escherichia coli and Klebsiella pneumoniae at two
      North Indian hospitals and to determine the risk factors associated with the
      acquisition of these organisms. A total of 346 bacterial isolates were obtained.
      Of these, 48.27% (n = 167) were confirmed to be ESBL producers while 51.73% (n =
      179) were non ESBL-producers. Among the ESBL producers, 55.69% (n = 93) were E.
      coli and 44.31% (n = 74) were K. pneumoniae. ESBL producing isolates showed co
      resistance to multitude of antibiotics tested. Length of hospital stay (>3 days)
      and previous exposure to antibiotics were found as significant risk factors (p =
      0.01 and 0.02) associated with the acquisition of ESBL-producing E. coli and K.
      pneumoniae isolates. Imipenem and meropenem can be suggested as drugs of choice
      in our study. 

PMID- 25561882
TI  - Improved efficiency and stability of secnidazole - An ideal delivery system.
AB  - Secnidazole (alpha,2-Dimethyl-5-nitro-1H-imidazole-1-ethanol) is a highly
      effective drug against a variety of G(+)/G(-) bacteria but with significant side
      effects because it is being used in very high concentration. In this study, gold
      nanoparticles (GNPS) were selected as a vehicle to deliver secnidazole drug at
      the specific site with more accuracy which made the drug highly effective at
      substantially low concentrations. The as-synthesized GNPs were capped with Human
      Serum Albumin (HSA) and subsequently bioconjugated with secnidazole because HSA
      provides the stability and improves the solubility of the bioconjugated drug,
      secnidazole. The quantification of covalently bioconjugated secnidazole with HSA
      encapsulated on enzymatically synthesized GNPs was done with RP-HPLC having SPD
      20 A UV/VIS detector by using the C-18 column. The bioconjugation of GNPs with
      secnidazole was confirmed by Transmission Electron Microscopy (TEM) and Dynamic
      Light Scattering (DLS). The bioconjugated GNPs were characterized by UV-VIS
      spectroscopy, TEM, Scanning Electron Microscopy (SEM) and DLS. Zeta potential
      confirmed the stability and uniform distribution of particles in the emulsion of
      GNPs. The separation of bioconjugated GNPs, unused GNPs and unused drug was done
      by gel filtration chromatography. The minimal inhibitory concentration of
      secnidazole-conjugated gold nanoparticles (Au-HSA-Snd) against Klebsiella
      pneumonia (NCIM No. 2957) and Bacillus cereus (NCIM No. 2156) got improved by
      12.2 times and 14.11 times, respectively, in comparison to pure secnidazole.
      Precisely, the MIC of Au-HSA-Snd against K. pneumonia (NCIM No. 2957) and B.
      cereus (NCIM No. 2156) were found to be 0.35 and 0.43 MUg/ml, respectively
      whereas MIC of the pure secnidazole drug against the same bacteria were found to
      be 4.3 and 6.07 MUg/ml, respectively. 

PMID- 25561883
TI  - The association of nutritional profile and prognosis of degenerative diseases
      associated with carbohydrate and lipid metabolism at high altitude of district
      Ziarat, Pakistan.
AB  - OBJECTIVE: In the present study the physiological parameters, their comparative
      analysis with carbohydrate and lipid metabolism were studied. This study suggests
      life style, environmental and genetic adaptations in the studied population.
      METHOD: One hundred and ninety eight subjects were selected from different towns
      of District Ziarat. General characteristics of the population according to their
      nutritional habits including, age, body mass index(BMI), systolic blood pressure,
      diastolic blood pressure, glycemia, triglycerides, serum low density lipoprotein
      (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL),
      triglycerides (TG) were measured. RESULTS: Mean cholesterol, LDL, VLDL and
      triglyceride values were significantly higher in men than women and the values
      increased with increasing age in both men and women. HDL and glucose values were
      significantly higher in females than males. In men with various nutritional
      groups such as A, B and C, the mean cholesterol (P < 0.001), LDL (P < 0.014),
      VLDL (P < 0.031) and triglyceride (P < 0.025) levels were significantly observed
      among comparable groups. However, in women with various nutritional groups such
      as A, B and C, the mean age (P < 0.047) and triglyceride values (P < 0.033)
      display statistically significant results.

PMID- 25561884
TI  - Comparative study of high sensitivity troponin T and heart-type fatty acid
      binding protein in STEMI patients.
AB  - AIM AND BACKGROUND: Heart-type fatty acid-binding proteins (H-FABP) which are
      detected within 2-3 h of acute myocardial infarction are involved in uptake of
      free fatty acids in the myocardium. Our aim in the present study is to compare
      window periods of H-FABP to high sensitivity troponin T (hs-Trop T) in acute ST
      elevation myocardial infarction (STEMI). METHODS: 160 STEMI diagnosed patient's
      serum samples are analyzed for hs-Trop T and H-FABP. Different window periods of
      chest pain onset (<3 h, 3-6 h and >6 h) are compared with complications, in
      hospital mortality and statistically analyzed. RESULTS: From 160 patients, 53
      (33%) cases are presented in <3 h, 75 (47%) in 3-6, and 32 (20%) after >6 h
      respectively. Accordingly sensitivity of hs-Trop T was 92%, 94% and 97% while H
      FABP was 75%, 88% and 84%, respectively. Overall sensitivity was 94% and 82%
      respectively. Statistically significant difference between mean hs-Trop T values
      with respect to window period <3, 3-6 and >6 h was 0.21, 0.35 and 0.80 ng/ml
      respectively, p value < 0.0001. No significant difference in H-FABP values was
      observed. Hs-Trop T positively correlated with age (r = 0.153, P = 0.05), window
      period (r = 0.363, P < 0.0001), TIMI score (r = 0.208, P = 0.008), ejection
      fraction (r = 0.191, P = 0.008), serum H-FABP (r = 0.229, P = 0.004), and serum
      hs-CRP (r = 0.326, p < 0.001). There was a statistically significant difference
      of mean hs-Trop T values with or without in hospital mortality (0.35 vs. 0.85
      ng/ml, respectively, p = 0.008). No significant correlation to age, TIMI score,
      ejection fraction and hs-CRP values for H-FABP was observed. CONCLUSION: It
      appears that hs-Trop T is a more sensitive marker than H-FABP in early hours of
      AMI and higher hs-Trop T predicts increase in-hospital mortality.

PMID- 25561885
TI  - Prevalence of multidrug resistant and extended spectrum beta-lactamase producing
      Pseudomonas aeruginosa in a tertiary care hospital.
AB  - Resistance to broad-spectrum beta-lactams, mediated by extended-spectrum beta
      lactamase enzymes (ESBL), is an increasing problem worldwide. The present study
      was undertaken to determine the incidence of ESBL-production among the clinical
      isolates of Pseudomonas aeruginosa and their susceptibility to selected
      antimicrobials. A total of one eighty-seven clinical specimens were tested for
      the presence of ESBL production using the double-disc synergy test. Of these,
      25.13% (n = 47) isolates of P. aeruginosa were observed as ESBL positive. The
      maximum number of ESBL-producing strains were found in sputum (41.67%; n = 24)
      followed by pus (28.36%; n = 19), cerebrospinal fluid and other body fluids
      (21.74%; n = 5), urine (20.45%; n = 9) and blood (13.79%; n = 4). ESBL producing
      isolates exhibited co-resistance to an array of antibiotics tested. Imipenem and
      meropenem can be suggested as the drugs of choice in our study. 

PMID- 25561886
TI  - Assessment of the role of general, biochemical and family history characteristics
      in kidney stone formation.
AB  - AIM: The main objective of the study was to determine the urinary risk factors
      involved in kidney stone formation. METHOD: In this study a total number of 101
      patients (64 males and 37 females) between the age group 2 and 70 years were
      selected. Personal characteristics like age, family history, clinical sign and
      symptoms, education, monthly income, living style, smoking or tobacco chewing
      habit, dietary intake and daily amount of drinking water were recorded. RESULTS:
      The study showed that the risk of kidney stone formation was high in the median
      age group (16-25 years) both in male and female population. The most important
      factors associated with this were lack of drinking clean water, over weight and
      obesity as well as family history (37.5% and 27.02% in men and women,
      respectively). CONCLUSION: Our study has confirmed that lack of drinking
      sufficient amount of water, increasing weight and obesity and family history are
      some major factors contributing to the increased risk of kidney stone formation.
      Therefore it is very important to live a healthy life, drink clean water and
      control weight to prevent such diseases.

PMID- 25561887
TI  - Differential effects of anti-cancer and anti-hepatitis drugs on liver cystatin.
AB  - The drug-protein interaction has been the subject of increasing interest over the
      decades. In the present communication, the interaction of liver cystatin with
      anti-cancer (adriamycin) and anti-hepatitis (adevofir dipivoxil) drugs was
      studied by thiol-protease inhibitory assay, UV absorption, fluorescence
      spectroscopy and circular dichroism (CD). A static type of quenching was observed
      between the protein and the drug molecules. Binding constant (Ka) of adriamycin
      to liver cystatin (LC) was found to be 1.08 * 10(6) M(-1). Moreover, binding site
      number was found to be 2. Importantly, cystatin loses its activity in the
      presence of adriamycin. However, intrinsic fluorescence studies in the presence
      of adevofir dipivoxil showed enhancement in the fluorescence intensity suggesting
      that binding of adevofir to LC caused unfolding of the protein. The unfolding of
      the test protein was also accompanied by significant loss of inhibitory activity.
      CD spectroscopy result showed, both adriamycin and adevofir dipivoxil caused
      perturbation in the secondary structure of liver cystatin. The possible
      implications of these results will help in combating drug induced off target
      effects. 

PMID- 25561889
TI  - Studies on the role of goat heart galectin-1 as a tool for detecting post
      malignant changes in glycosylation pattern.
AB  - Galectins are mammalian lectins established to play a crucial role in the
      progression of various cancer types by the virtue of their differential
      expression in normal and cancerous cells. In the present study, goat heart
      galectin-1 (GHG-1) was purified and investigated for its potential role in the
      detection of post-malignant changes in glycosylation pattern. When exposed to
      superoxide radicals generated from a pyrogallol auto-oxidation system, GHG-1
      treated erythrocyte suspension released higher amount of oxyhemoglobin than the
      unagglutinated erythrocytes. The extent of erythrocyte hemolysis was found to be
      directly proportional to concentrations of hypochlorous acid. GHG-1 was used to
      detect the change in the beta-galactoside expression pattern in erythrocyte
      membrane from human donors suffering from prostate and breast cancer. No
      significant change was observed in the hemolysis of lectin agglutinated
      erythrocytes collected from pre-operated breast cancer patients, whereas
      significant increase was observed in normal healthy control and post-operated
      samples. Findings of this study proclaim GHG-1 as an important tool for the
      detection of post-malignant changes in glycosylation pattern. 

PMID- 25561888
TI  - Experimental model for ELF-EMF exposure: Concern for human health.
AB  - Low frequency (LF) electromagnetic fields (EMFs) are abundantly present in modern
      society and in the last 20 years the interest about the possible effect of
      extremely low frequency (ELF) EMFs on human health has increased progressively.
      Epidemiological studies, designed to verify whether EMF exposure may be a
      potential risk factor for health, have led to controversial results. The possible
      association between EMFs and an increased incidence of childhood leukemia, brain
      tumors or neurodegenerative diseases was not fully elucidated. On the other hand,
      EMFs are widely used, in neurology, psychiatry, rheumatology, orthopedics and
      dermatology, both in diagnosis and in therapy. In vitro studies may help to
      evaluate the mechanism by which LF-EMFs affect biological systems. In vitro model
      of wound healing used keratinocytes (HaCaT), neuroblastoma cell line (SH-SY5Y) as
      a model for analysis of differentiation, metabolism and functions related to
      neurodegenerative processes, and monocytic cell line (THP-1) was used as a model
      for inflammation and cytokines production, while leukemic cell line (K562) was
      used as a model for hematopoietic differentiation. MCP-1, a chemokine that
      regulates the migration and infiltration of memory T cells, natural killer (NK),
      monocytes and epithelial cells, has been demonstrated to be induced and involved
      in various diseases. Since, varying the parameters of EMFs different effects may
      be observed, we have studied MCP-1 expression in HaCaT, SH-SY5Y, THP-1 and K562
      exposed to a sinusoidal EMF at 50 Hz frequency with a flux density of 1 mT (rms).
      Our preliminary results showed that EMF-exposure differently modifies the
      expression of MCP-1 in different cell types. Thus, the MCP-1 expression needs to
      be better determined, with additional studies, with different parameters and
      times of exposure to ELF-EMF. 

PMID- 25561891
TI  - Lateral meningocele with asymmetric canal stenosis: A case study.
AB  - Lateral meningocele is a very rare disorder of unknown aetiology typified by the
      presence of protrusions of the arachnoid and the dura matter extending laterally
      through inter- or intra-vertebral foramina. We report here the case of a 52-year
      old male with abnormality of spine when presented with low back pain. The patient
      did not appear to have any neurological disorder. A computerized tomography (CT)
      scan was acquired from T12 to mid sacrum with multiplanar reformations. The
      results showed the presence of a left sided paraspinal cystic lesion projecting
      from the left neural foramen and extending into the left psoas muscle suggesting
      a lateral meningocele. In addition, a broad based central and left paracentral
      disc protrusion was also observed resulting in asymmetric canal stenosis. The
      patient is on regular follow-up while undergoing palliative treatment. 

PMID- 25561890
TI  - Antibiotic resistance and extended spectrum beta-lactamases: Types, epidemiology
      and treatment.
AB  - Antibiotic resistance is a problem of deep scientific concern both in hospital
      and community settings. Rapid detection in clinical laboratories is essential for
      the judicious recognition of antimicrobial resistant organisms. Production of
      extended-spectrum beta-lactamases (ESBLs) is a significant resistance-mechanism
      that impedes the antimicrobial treatment of infections caused by
      Enterobacteriaceae and is a serious threat to the currently available antibiotic
      armory. ESBLs are classified into several groups according to their amino acid
      sequence homology. Proper infection control practices and barriers are essential
      to prevent spread and outbreaks of ESBL producing bacteria. As bacteria have
      developed different strategies to counter the effects of antibiotics, the
      identification of the resistance mechanism may help in the discovery and design
      of new antimicrobial agents. The carbapenems are widely regarded as the drugs of
      choice for the treatment of severe infections caused by ESBL-producing
      Enterobacteriaceae, although comparative clinical trials are scarce. Hence, more
      expeditious diagnostic testing of ESBL-producing bacteria and the feasible
      modification of guidelines for community-onset bacteremia associated with
      different infections are prescribed. 

PMID- 25561892
TI  - Assessment of circulating biochemical markers and antioxidative status in acute
      lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients.
AB  - Various circulating biochemical markers are indicators of pathological state in
      leukemia and its subtypes. Increased oxidative stress and decreased antioxidant
      factors portray clear image associated with malignancies during subtypes of
      leukemia. In this research work we investigated the inter-relationship among the
      subtypes of leukemia with circulating biochemical markers and oxidative stress in
      the Pakistani population. This research work was conducted on a total number of
      70 subjects in which 20 were control participants and 50 were suffering from
      leukemia and divided into two subtypes (ALL and AML). Various circulating
      biomarkers were investigated including hematological, hepatic and renal profiles
      as well as oxidative stress markers, electrolytes and vitamins C and E. Results
      show that vitamin E was found to be decreased in diseased sub-types (P < 0.05).
      Malondialdehyde (MDA) levels were very high in disease sub-types (ALL-B = 8.69 +/
      1.59; ALL-T = 8.78 +/- 0.97; AML = 8.50 +/- 1.29) compared to controls (1.22 +/-
      0.10; P < 0.05) while the levels of antioxidants [superoxide dismutase (SOD),
      glutathione peroxidase (GPx), reduced glutathione (GSH), catalase (CAT)],
      platelets, as well as electrolytes (Ca and Mg) were reduced in patients suffering
      from leukemia (sub-types). Enhanced levels of oxidative stress (MDA) and
      decreased levels of enzymatic and non-enzymatic antioxidants reflect the
      pathological state and impaired cell control in patients suffering from leukemia
      (subtypes) and show a strong correlation with oxidative stress, indicating that
      patients' biological systems are under oxidative stress. 

PMID- 25561893
TI  - Studies on the role of goat heart galectin-1 as an erythrocyte membrane
      perturbing agent.
AB  - Galectins are beta-galactoside binding lectins with a potential hemolytic role on
      erythrocyte membrane integrity and permeability. In the present study, goat heart
      galectin-1 (GHG-1) was purified and investigated for its hemolytic actions on
      erythrocyte membrane. When exposed to various saccharides, lactose and sucrose
      provided maximum protection against hemolysis, while glucose and galactose
      provided lesser protection against hemolysis. GHG-1 agglutinated erythrocytes
      were found to be significantly hemolyzed in comparison with unagglutinated
      erythrocytes. A concentration dependent rise in the hemolysis of trypsinized
      rabbit erythrocytes was observed in the presence of GHG-1. Similarly, a
      temperature dependent gradual increase in percent hemolysis was observed in GHG-1
      agglutinated erythrocytes as compared to negligible hemolysis in unagglutinated
      cells. The hemolysis of GHG-1 treated erythrocytes showed a sharp rise with the
      increasing pH up to 7.5 which became constant till pH 9.5. The extent of
      erythrocyte hemolysis increased with the increase in the incubation period, with
      maximum hemolysis after 5 h of incubation. The results of this study establish
      the ability of galectins as a potential hemolytic agent of erythrocyte membrane,
      which in turn opens an interesting avenue in the field of proteomics and
      glycobiology. 

PMID- 25561894
TI  - Treatment of psoriasis by using Hijamah: A case report.
AB  - Hijamah (a well-known Prophetic complimentary treatment) has been used for
      centuries to treat various human diseases. It is considered that this traditional
      treatment (also known as wet cupping) has the potential to treat many kinds of
      diseases. It is performed by creating a vacuum on the skin by using a cup to
      collect the stagnant blood in that particular area. The vacuum at the end is
      released by removing the cup. Superficial skin scarification is then made to draw
      the blood stagnation out of the body. This technique needs to be performed in
      aseptic conditions by a well trained Hijamah-physician. Prophet Muhammad (PBUH)
      had described Hijamah as the best treatment humans can have. This novel treatment
      methodology has been successfully used as cure for numerous diseases including
      skin diseases. In this case report, we discuss about the application of this
      method in the treatment of psoriasis (an autoimmune skin disease). Results
      illustrated that with Hijamah, disease can not only be controlled but can be
      brought to a nearly complete remission. 

PMID- 25561895
TI  - Stanniocalcin-1 controls ion regulation functions of ion-transporting epithelium
      other than calcium balance.
AB  - Stanniocalcin-1 (STC-1) was first identified to involve in Ca(2+) homeostasis in
      teleosts, and was thought to act as a hypocalcemic hormone in vertebrate. Recent
      studies suggested that STC-1 exhibits broad effects on ion balance, not confines
      to Ca(2+), but the mechanism of this regulation process remains largely unknown.
      Here, we used zebrafish embryos as an alternative in vivo model to investigate
      how STC-1 regulates transepithelial ion transport function in ion-transporting
      epithelium. Expression of stc-1 mRNA in zebrafish embryos was increased in high
      Ca(2+) environments but decreased by acidic and ion-deficient treatments while
      overexpression of stc-1 impaired the hypotonic acclimation by decreasing whole
      body Ca(2+), Na(+), and Cl(-) contents and H(+) secretion ability. Injection of
      STC-1 mRNA also down-regulated mRNA expressions of epithelial Ca(2+) channel,
      H(+)-ATPase, and Na(+)-Cl(-) cotransporter, suggesting the roles of STC-1 in
      regulation of ions other than Ca(2+). Knockdown of STC-1 caused an increase in
      ionocyte progenitors (foxi3a as the marker) and mature ionocytes (ion
      transporters as the markers), but did not affect epithelium stem cells (p63 as
      the marker) in the embryonic skin. Overexpression of STC-1 had the corresponding
      opposite effect on ionocyte progenitors, mature ionocytes in the embryonic skin.
      Taken together, STC-1 negatively regulates the number of ionocytes to reduce
      ionocyte functions. This process is important for body fluid ionic homeostasis,
      which is achieved by the regulation of ion transport functions in ionocytes. The
      present findings provide new insights into the broader functions of STC-1, a
      hypocalcemic hormone. 

PMID- 25561896
TI  - Adipose-derived stromal cells protect intervertebral disc cells in compression:
      implications for stem cell regenerative disc therapy.
AB  - INTRODUCTION: Abnormal biomechanics plays a role in intervertebral disc
      degeneration. Adipose-derived stromal cells (ADSCs) have been implicated in disc
      integrity; however, their role in the setting of mechanical stimuli upon the
      disc's nucleus pulposus (NP) remains unknown. As such, the present study aimed to
      evaluate the influence of ADSCs upon NP cells in compressive load culture.
      METHODS: Human NP cells were cultured in compressive load at 3.0MPa for 48 hours
      with or without ADSCs co-culture (the ratio was 50:50). We used flow cytometry,
      live/dead staining and scanning electron microscopy (SEM) to evaluate cell death,
      and determined the expression of specific apoptotic pathways by characterizing
      the expression of activated caspases-3, -8 and -9. We further used real-time (RT
      ) PCR and immunostaining to determine the expression of the extracellular matrix
      (ECM), mediators of matrix degradation (e.g. MMPs, TIMPs and ADAMTSs), pro
      inflammatory factors and NP cell phenotype markers. RESULTS: ADSCs inhibited
      human NP cell apoptosis via suppression of activated caspase-9 and caspase-3.
      Furthermore, ADSCs protected NP cells from the degradative effects of compressive
      load by significantly up-regulating the expression of ECM genes (SOX9, COL2A1 and
      ACAN), tissue inhibitors of metalloproteinases (TIMPs) genes (TIMP-1 and TIMP-2)
      and cytokeratin 8 (CK8) protein expression. Alternatively, ADSCs showed
      protective effect by inhibiting compressive load mediated increase of matrix
      metalloproteinases (MMPs; MMP-3 and MMP-13), disintegrin and metalloproteinase
      with thrombospondin motifs (ADAMTSs; ADAMTS-1 and 5), and pro-inflammatory
      factors (IL-1beta, IL-6, TGF-beta1 and TNF-alpha). CONCLUSIONS: Our study is the
      first in vitro study assessing the impact of ADSCs on NP cells in an un
      physiological mechanical stimulation culture environment. Our study noted that
      ADSCs protect compressive load induced NP cell death and degradation by
      inhibition of activated caspase-9 and -3 activity; regulating ECM and modulator
      genes, suppressing pro-inflammatory factors and preserving CK8. Consequently, the
      protective impact of ADSCs found in this study provides an essential
      understanding and expands our knowledge as to the utility of ADSCs therapy for
      intervertebral disc regeneration.

PMID- 25561897
TI  - Clinical significance of a point mutation in DNA polymerase beta (POLB) gene in
      gastric cancer.
AB  - Gastric cancer (GC) is a major cause of global cancer mortality. Genetic
      variations in DNA repair genes can modulate DNA repair capability and,
      consequently, have been associated with risk of developing cancer. We have
      previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA
      polymerase beta (POLB) gene, a key enzyme involved in base excision repair in
      primary GCs. The purpose of this study was to evaluate the mutation and
      expression of POLB in a larger cohort and to identify possible prognostic roles
      of the POLB alterations in GC. Primary GC specimens and their matched normal
      adjacent tissues were collected at the time of surgery. DNA, RNA and protein
      samples were isolated from GC specimens and cell lines. Mutations were detected
      by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by
      RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The
      function of the mutation was evaluated by chemosensitivity, MTT, Transwell
      matrigel invasion and host cell reactivation assays. The T889C mutation was
      detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated
      with POLB overexpression, lymph nodes metastases and poor tumor differentiation.
      In addition, patients with- the mutation had significantly shorter survival time
      than those without-, following postoperative chemotherapy. Furthermore, cell
      lines with T889C mutation in POLB gene were more resistant to the treatment of 5
      fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced
      expression of POLB gene with T889C mutation resulted in enhanced cell
      proliferation, invasion and resistance to anticancer drugs, along with increased
      DNA repair capability. These results suggest that POLB gene with T889C mutation
      in surgically resected primary gastric tissues may be clinically useful for
      predicting responsiveness to chemotherapy in patients with GC. The POLB gene
      alteration may serve as a prognostic biomarker for GC. 

PMID- 25561898
TI  - Effects of nitric oxide on notexin-induced muscle inflammatory responses.
AB  - Excessive inflammatory response may delay the regeneration and damage the normal
      muscle fibers upon myoinjury. It would be important to be able to attenuate the
      inflammatory response and decrease inflammatory cells infiltration in order to
      improve muscle regeneration formation, resulting in better muscle functional
      recovery after myoinjury. This study was undertaken to explore the role of Nitric
      oxide (NO) during skeletal muscle inflammatory process, using a mouse model of
      Notexin induced myoinjury. Intramuscular injection (tibialis anterior, TA) of
      Notexin was performed for preparing mice myoinjury. NO synthase inhibitor (L
      NAME) or NO donor (SNP) was intraperitoneally injected into model mice. On day 4
      and 7 post-injury, expression of muscle-autoantigens and toll-like receptors
      (TLRs) was evaluated from muscle tissue by qRT-PCR and Western Blot; the
      intramuscular infiltration of monocytes/macrophage (CD11b(+) or F4/80(+) cells),
      CD8(+) T cell (CD3epsilon(+)CD8alpha(+)), apoptotic cell (CD11b(+)caspase3(+)),
      and MHC-I molecule H-2K(b)-expressing myofibers in damaged muscle were assessed
      by imunoflourecence analysis; the mRNAs expression of cytokines and chemokines
      associated with the preferential biological role during the muscle damage-induced
      inflammation response, were assessed by qRT-PCR. We detected the reduced
      monocytes/macrophages infiltration, and increased apoptotic cells in the damaged
      muscle treated with SNP comparing to untreatment. As well, SNP treatment down
      regulated mRNA and protein levels of muscle autoantigens, TLR3, and mRNA levels
      of TNF-alpha, IL-6, MCP-1, MCP-3, and MIP-1alpha in damaged muscle. On the
      contrary, L-NAME induced more severe intramuscular infiltration of inflammatory
      cells, and mRNA level elevation of the above inflammatory mediators. Notably, we
      observed an increased number of MHC-I (H2-K(b)) positive new myofibers, and of
      the infiltrated CD8(+) T cells in damaged muscle at the day 7 after L-NAME
      treatment. The result herein shows that, NO can act as an endogenous anti
      inflammatory molecule during the ongoing muscle inflammation. Our finding may
      provide new insight to optimize NO-based therapies for improving muscle
      regeneration after myoinjury. 

PMID- 25561900
TI  - Enhancement of larval RNAi efficiency by over-expressing Argonaute2 in Bombyx
      mori.
AB  - RNA interference has been described as a powerful genetic tool for gene
      functional analysis and a promising approach for pest management. However, RNAi
      efficiency varies significantly among insect species due to distinct RNAi
      machineries. Lepidopteran insects include a large number of pests as well as
      model insects, such as the silkworm, Bombyx mori. However, only limited success
      of in vivo RNAi has been reported in lepidoptera, particularly during the larval
      stages when the worms feed the most and do the most harm to the host plant.
      Enhancing the efficiency of larval RNAi in lepidoptera is urgently needed to
      develop RNAi-based pest management strategies. In the present study, we
      investigate the function of the conserved RNAi core factor, Argonaute2 (Ago2), in
      mediating B. mori RNAi efficiency. We demonstrate that introducing BmAgo2 dsRNA
      inhibits the RNAi response in both BmN cells and embryos. Furthermore, we
      establish several transgenic silkworm lines to assess the roles of BmAgo2 in
      larval RNAi. Over-expressing BmAgo2 significantly facilitated both dsRNA-mediated
      larval RNAi when targeting DsRed using dsRNA injection and shRNA-mediated larval
      RNAi when targeting BmBlos2 using transgenic shRNA expression. Our results show
      that BmAgo2 is involved in RNAi in B. mori and provides a promising approach for
      improving larval RNAi efficiency in B. mori and in lepidopteran insects in
      general. 

PMID- 25561899
TI  - Biology of IL-27 and its role in the host immunity against Mycobacterium
      tuberculosis.
AB  - IL-27, a heterodimeric cytokine of IL-12 family, regulates both innate and
      adaptive immunity largely via Jak-Stat signaling. IL-27 can induce IFN-gamma and
      inflammatory mediators from T lymphocytes and innate immune cells. IL-27 has
      unique anti-inflammatory properties via both Tr1 cells dependent and independent
      mechanisms. Here the role and biology of IL-27 in innate and adaptive immunity
      are summarized, with special interest with immunity against Mycobacterium
      tuberculosis. 

PMID- 25561901
TI  - FOXM1 promotes lung adenocarcinoma invasion and metastasis by upregulating SNAIL.
AB  - The forkhead box M1 (FOXM1) transcription factor is one of the key genes inducing
      tumor invasion and metastasis by an unknown mechanism. In this study, we set out
      to investigate the effects of FOXM1 overexpression on metastatic human lung
      adenocarcinoma and the underlying mechanism. FOXM1 expression was analyzed in 78
      frozen lung adenocarcinoma tissue samples using an Affymetrix microarray and a
      155-paraffin-embedded lung adenocarcinoma tissue microarray with
      immunohistochemical detection. FOXM1 was found to be overexpressed in lung
      adenocarcinoma, particularly in metastatic patients, compared to non-metastatic
      patients. Knockdown of FOXM1 by a specific siRNA significantly suppressed EMT
      progression, migration and invasion of lung adenocarcinoma cells in vitro, and
      tumor growth and metastasis in vivo, whereas restored expression of FOXM1 had the
      opposite effect. FOXM1 binds directly to the SNAIL promoter through two specific
      binding sites and constitutively transactivates it. Collectively, our findings
      indicate that FOXM1 may play an important role in advancing lung adenocarcinoma
      progression. Aberrant FOXM1 expression directly and constitutively activates
      SNAIL, thereby promoting lung adenocarcinoma metastasis. Inhibition of FOXM1
      SNAIL signaling may present an ideal target for future treatment. 

PMID- 25561902
TI  - A soluble activin receptor type IIB does not improve blood glucose in
      streptozotocin-treated mice.
AB  - Type 1 diabetes mellitus (T1DM), or insulin dependent DM, is accompanied by
      decreased muscle mass. The growth factor myostatin (MSTN) is a negative regulator
      of muscle growth, and a loss of MSTN signaling has been shown to increase muscle
      mass and prevent the development of obesity, insulin resistance and
      lipodystrophic diabetes in mice. The effects of MSTN inhibition in a T1DM model
      on muscle mass and blood glucose are unknown. We asked whether MSTN inhibition
      would increase muscle mass and decrease hyperglycemia in mice treated with
      streptozotocin (STZ) to destroy pancreatic beta cells. After diabetes developed,
      mice were treated with a soluble MSTN/activin receptor fused to Fc (ACVR2B:Fc).
      ACVR2B:Fc increased body weight and muscle mass compared to vehicle treated mice.
      Unexpectedly, ACVR2B:Fc reproducibly exacerbated hyperglycemia within
      approximately one week of administration. ACVR2B:Fc treatment also elevated serum
      levels of the glucocorticoid corticosterone. These results suggest that although
      MSTN/activin inhibitors increased muscle mass, they may be counterproductive in
      improving health in patients with T1DM. 

PMID- 25561903
TI  - Identification and functional analysis of a novel tryptophyllin peptide from the
      skin of the red-eye leaf frog, Agalychnis callidryas.
AB  - Amphibian skin has proved repeatedly to be a largely untapped source of bioactive
      peptides and this is especially true of members of the Phyllomedusinae subfamily
      of frogs native to South and Central America. Tryptophyllins are a group of
      peptides mainly found in the skin of members of this genus. In this study, a
      novel tryptophyllin (TPH) type 3 peptide, named AcT-3, has been isolated and
      structurally-characterised from the skin secretion and lyophilised skin extract
      of the red-eye leaf frog, Agalychnis callidryas. The peptide was identified in
      and purified from the skin secretion by reverse-phase HPLC. MALDI-TOF mass
      spectrometry and MS/MS fragmentation sequencing established its primary structure
      as: pGlu-Gly-Lys-Pro-Tyr-Trp-Pro-Pro-Pro-Phe-Leu-Pro-Glu, with a non-protonated
      molecular mass of 1538.19Da. The mature peptide possessed the canonical N
      terminal pGlu residue that arises from post-translational modification of a Gln
      residue. The deduced open-reading frame consisted of 63 amino acid residues
      encoding a highly-conserved signal peptide of approximately 22 amino acid
      residues, an intervening acidic spacer peptide domain, a single AcT-3 encoding
      domain and a C terminal processing site. A synthetic replicate of AcT-3 was found
      to antagonise the effect of BK on rat tail artery smooth muscle and to contract
      the intestinal smooth muscle preparations. It was also found that AcT-3 could
      dose-dependently inhibit the proliferation of human prostate cancer cell lines
      after 72h incubation. 

PMID- 25561906
TI  - "Annual pharma statistics" as a health information system application in Iranian
      pharmaceutical sector.

PMID- 25561904
TI  - Changes in follicular helper T cells in idiopathic thrombocytopenic purpura
      patients.
AB  - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is a primary autoimmune
      disease with a decreased platelet count caused by platelet destruction mediated
      mainly by platelet antibodies. T follicular helper (TFH) cells have demonstrated
      important roles in autoimmune diseases. The aim of this study is to explore the
      might role of TFH cells in the patients of ITP. METHODS: Twenty-three ITP
      patients and 12 healthy controls (HC) were enrolled in this study. The frequency
      of circulating TFH cells in both the patients and HC was analyzed by flow
      cytometry. Serum interleukin (IL)-21 and IL-6 levels were measured using ELISA,
      and platelet antibodies were tested using a solid phase technique. Additionally,
      IL-21, IL-6, Bcl-6 and c-Maf mRNA expressions in peripheral blood mononuclear
      cells (PBMCs) were detected using real-time PCR. RESULTS: The percentages of
      circulating CXCR5(+) CD4(+)TFH cells with ICOS(high) or PD-1(high) expression
      were significantly higher in the ITP patients than in the HC. Moreover, the
      frequencies of circulating CXCR5(+) CD4(+)TFH cells with inducible costimulator
      (ICOS)(high) or programmed death-1 (PD-1)(high) expression were notably higher in
      ITP with platelet-antibody-positive ( ITP (+) ) patients than in ITP with
      platelet-antibody-negative ( ITP (-) ) patients and HC, as were the serum IL-21
      and IL-6 levels (significant). Moreover, a positive correlation was found between
      the CXCR5(+)CD4(+)TFH cells with ICOS(high) or PD-1(high) expression and the
      serum IL-21 levels of ITP (+) patients. Additionally, the mRNA expression levels
      of IL-21, IL-6, Bcl-6 and c-Maf were significantly increased in ITP patients,
      especially in ITP (+) patients. CONCLUSIONS: This study demonstrated TFH cells
      and effector molecules might play an important role in the pathogenesis of ITP,
      which are possible therapeutic targets in ITP patients.

PMID- 25561907
TI  - Size reproducibility of gadolinium oxide based nanomagnetic particles for
      cellular magnetic resonance imaging: effects of functionalization, chemisorption
      and reaction conditions.
AB  - We developed biofunctionalized nanoparticles with magnetic properties by
      immobilizing diethyleneglycol (DEG) on Gd2O3, and PEGilation of small particulate
      gadolinium oxide (SPGO) with two methoxy-polyethyleneglycol-silane (mPEG-Silane
      550 and 2000 Da) using a new supervised polyol route, described recently. In
      conjunction to the previous study to achieve a high quality synthesis and
      increase in the product yield of nanoparticles; assessment of the effects of
      functionalization, chemisorption and altered reaction conditions, such as NaOH
      concentration, temperature, reaction time and their solubility, on size
      reproducibility were determined as the goals of this study. Moreover, the effects
      of centrifugation, filtration and dialysis of the solution on the nono magnetic
      particle size values and their stability against aggregation have been evaluated.
      Optimization of reaction parameters led to strong coating of magnetic
      nanoparticles with the ligands which increases the reproducibility of particle
      size measurements. Furthermore, the ligand-coated nanoparticles showed enhanced
      colloidal stability as a result of the steric stabilization function of the
      ligands grafted on the surface of particles. The experiments showed that DEG and
      mPEG-silane (550 and 2000 Dalton) are chemisorbed on the particle surfaces of
      Gd2O3 and SPGO which led to particle sizes of 5.9 +/- 0.13 nm, 51.3 +/- 1.46 nm
      and 194.2 +/- 22.1 nm, respectively. The small size of DEG-Gd2O3 is acceptably
      below the cutoff of 6nm, enabling easy diffusion through lymphatics and
      filtration from kidney, and thus provides a great deal of potential for further
      in-vivo and in-vitro application. 

PMID- 25561905
TI  - Impulsivity and comorbid traits: a multi-step approach for finding putative
      responsible microRNAs in the amygdala.
AB  - Malfunction of synaptic plasticity in different brain regions, including the
      amygdala plays a role in impulse control deficits that are characteristics of
      several psychiatric disorders, such as ADHD, schizophrenia, depression and
      addiction. Previously, we discovered a locus for impulsivity (Impu1) containing
      the neuregulin 3 (Nrg3) gene, of which the level of expression determines levels
      of inhibitory control. MicroRNAs (miRNAs) are potent regulators of gene
      expression, and have recently emerged as important factors contributing to the
      development of psychiatric disorders. However, their role in impulsivity, as well
      as control of Nrg3 expression or malfunction of the amygdala, is not well
      established. Here, we used the GeneNetwork database of BXD mice to search for
      correlated traits with impulsivity using an overrepresentation analysis to filter
      for biologically meaningful traits. We determined that inhibitory control was
      significantly correlated with expression of miR-190b, -28a, -340, -219a, and -491
      in the amygdala, and that the overrepresented correlated traits showed a specific
      pattern of coregulation with these miRNAs. A bioinformatics analysis identified
      that miR-190b, by targeting an Nrg3-related network, could affect synaptic
      plasticity in the amygdala, targeting bot impulsive and compulsive traits.
      Moreover, miR-28a, -340, -219a, and possibly -491 could act on synaptic function
      by determining the balance between neuronal outgrowth and differentiation. We
      propose that these miRNAs are attractive candidates of regulation of amygdala
      synaptic plasticity, possibly during development but also in maintaining the
      impulsive phenotype. These results can help us to better understand mechanisms of
      synaptic dysregulation in psychiatric disorders. 

PMID- 25561908
TI  - Novel patchouli alcohol ternary solid dispersion pellets prepared by poloxamers.
AB  - The present study investigates the possibility of using poloxamers as solubility
      and dissolution rate enhancing agents of poorly water soluble bioactive
      constituent patchouli alcohol (PA) that can be used for the preparation of
      immediate release pellets formulation. Two commercially available grades
      poloxamer 188 (P 188) and poloxamer 407 (P 407) were selected, and solid
      dispersions (SDs) containing different weight ratio of PA and poloxamers, and the
      combination of P 188 and P 407 as dispersing carriers of ternary solid
      dispersions (tSDs) were prepared by a low temperature melting method and
      solidified rapidly by dropping into the 10-15  degrees C condensing agent
      atoleine. Both PA/P 188 and PA/P 407 binary solid dispersions (bSDs) could
      remarkably promote the dissolution rate of PA, increasing approximately 16 times
      in bSDs with poloxamers in comparison with pure PA within 180 min. P188
      contributed to a faster dissolution rate than P 407, however, P 407 had a better
      solubility. It is interesting to note that the incorporation of P 188 in PA/P 407
      bSD pellets could strongly enhance the dissolution rate of PA. DSC and FTIR were
      used to explore the characteristics of PA-SD pellets. The enhancement of
      dissolution from the SDs may be attributed partly to the reduction in particle
      size in PA crystalline due to the formation of eutectic system with poloxamers.
      Moreover, a simple, accurate in-vitro dissolution test method for volatility drug
      was established, and the process of PA-SD pellets preparation was simple, rapid,
      cost effective, uncomplicated and potentially scalable. 

PMID- 25561909
TI  - Preparation and characterization of rifampin loaded mesoporous silica
      nanoparticles as a potential system for pulmonary drug delivery.
AB  - The goal of this research is to determine the feasibility of loading rifampin
      into mesoporous silica nanoparticles. Rifampin was selected as a model lipophilic
      molecule since it is a well-documented and much used anti tuberculosis drug. The
      mesoporous silica nanoparticles were prepared by using tetraethyl ortho silicate
      and cetyltrimethyl ammonium bromide (as surfactant). The prepared nanoparticles
      were characterized in terms of their particle size measurement and porosimetry.
      The results showed that the particle size is 218 +/- 46 nm (mean +/- SD) and
      surface area is 816 m(2)g(-1). In order to load rifampin within the mesopores,
      adsorption experiments using three different solvents (methanol, water and
      dimethyl sulfoxide) were carried out. The loading procedure resulted in a
      significant improvement in the amount of rifampin loaded into mesoporous silica
      nanoparticles and methanol was found to be a suitable solvent, providing a drug
      entrapment efficiency of 52 %. Rifampin loaded nanoparticles underwent different
      in-vitro tests including, SEM and drug release. The in-vitro drug release was
      investigated using buffer phosphate (pH=7.4). Regarding the drug release study, a
      biphasic pattern of release was observed. The drug-loaded mesoporous silica
      nanoparticles were capable of releasing 95% of their drug content after 24 h,
      following a faster release in the first four hours. The prepared rifampin loaded
      nanoparticles seem to have potential for use as a pulmonary drug delivery. 

PMID- 25561911
TI  - Effect of drying phase on the agglomerates prepared by spherical crystallization.
AB  - In this paper, differences in porosity, compressive strength and tablet- forming
      ability of carbamazepine crystals agglomerated under similar condition, but
      subjected to different drying temperatures are reported. The agglomerates were
      prepared by spherical crystallization method and thereafter dried without
      agitation at different temperature. An increased drying temperature did not
      affect the shape and structure texture of dried particles and did not cause them
      to fracture. Drying of particles at higher temperature suppressed the particle
      contraction as a consequence of fast evaporation and hence produced particles of
      larger mean diameter, higher porosity and thus lower compressive strength than
      those dried at lower temperature. Through a relationship with particle porosity,
      the drying rate also affected the ability of particles to form tablets. 

PMID- 25561910
TI  - Preparation and characterization of celecoxib dispersions in soluplus((r)):
      comparison of spray drying and conventional methods.
AB  - The present study deals with characterization of dispersions of a poorly water
      soluble drug, celecoxib (CLX) in polyvinyl caprolactame-polyvinyl acetate
      polyethylene glycol graft copolymer (Soluplus((r)) (SOL)) prepared by different
      techniques. Dispersions of CLX in SOL at different ratios (2:1, 1:1, 1:2, 1:4 and
      1:6) were prepared by spray drying, conventional solvent evaporation and melting
      methods. The solid states of samples were characterized using particle size
      measurements, optical and scanning electron microscopy, XRPD, DSC and FT-IR. The
      Gordon-Taylor equation was used to predict the Tg of samples and the possibility
      of interaction between CLX and SOL. The solubility and dissolution rate of all
      samples were determined. Stability of samples was studied at ambient conditions
      for a period of 12 months. DSC and XRPD analyses confirmed amorphous state of
      drug in samples. Surprisingly dispersions of CLX:SOL with the ratio of 2:1 and
      1:1 showed slower dissolution rate than CLX while other samples showed higher
      dissolution rate. At 1:2 ratio the spray dried samples exhibited higher
      dissolution rate than corresponding samples prepared by other methods. However at
      higher SOL content (1:4 and 1:6), samples prepared by different methods showed
      similar dissolution profiles. The stability studies showed that there were no
      remarkable changes in the dissolution profiles and solid state of the drug after
      12 months storage at ambient conditions. It was concluded that SOL was a proper
      carrier to enhance the dissolution rate of CLX. At high SOL ratios the method of
      preparation of dispersed samples had no effect on dissolution rate, whilst at low
      SOL content spray drying was more efficient method. 

PMID- 25561912
TI  - Design, Synthesis and Cytotoxicity Evaluationof New 1,2-diaryl-4, 5, 6, 7
      Tetrahydro-1H-benzo[d] Imidazolesas Tubulin Inhibitors.
AB  - A new series of 1,2-diaryl-4,5,6,7-tetrahydro-1H-benzo[d]imidazoles, possessing
      trimethoxyphenyl pharmacophore, were synthesized to evaluate their biological
      activities as tubulin inhibitors. Cytotoxic activity of the synthesized compounds
      7a-f was assessed against several human cancer cell lines, including MCF-7
      (breast cancer cell), HEPG2 (liver hepatocellular cells), A549 (adenocarcinomic
      human alveolar basal epithelial cells), T47D (Human ductal breast epithelial
      tumor cell line) and fibroblast. According to our results, HEPG2 seems to be the
      most sensitive, while MCF7 was the most resistant cell line to the compounds. All
      the compounds expect 7b, possessed satisfactory activity against HEPG2 with mean
      IC50 values ranging from 15.60 to 43.81 uM. 

PMID- 25561913
TI  - Synthesis, Characterization and Antibacterial Activity of some Novel
      Thiosemicarbazides, 1,2,4-Triazol-3-thiols and their S-substituted Derivatives.
AB  - The thiosemicarbazides 3a-c were appeared by reaction of the corresponding
      substituted hydrazides 1a-c with allylisothiocyanate 2. Synthesis of some novel
      1,2,4-triazole-thiols 4a-c bearing a pyridyl unit using 1-(x-picolinoyl)-4-allyl
      thiosemicarbazides (x = 2,3,4) in an alkaline solution, is reported. Also, the S
      alkylation of triazole derivatives 5-7a-c is described. The structure of the
      synthesized compounds resulted from the IR, (1)H and -(13)C NMR spectroscopy and
      elemental analysis data. The antibacterial studies to all of the synthesized
      compounds against B. cereus, E. coli, P. aeroginosa, S. aureus and E. faecalis as
      MIC values are reported. Some of these compounds such as 7a, 4a and 3a exhibited
      a good to significant antibacterial activity. 

PMID- 25561915
TI  - Synthesis and Antibacterial Evaluation of (S,Z)-4-methyl-2-(4-oxo-5-((5
      substituted phenylfuran-2-yl) methylene)-2-thioxothiazolidin-3-yl)Pentanoic
      Acids.
AB  - The microbial resistance has become a global hazard with the irrational use of
      antibiotics. Infection of drug-resistant bacteria seriously threatens human
      health. Currently, there is an urgent need for the development of novel
      antimicrobial agents with new mechanisms and lower levels of toxicity. In this
      paper, a series of (S ,Z)-4-methyl-2-(4-oxo-5-((5-substitutedphenylfuran-2-yl)
      methylene)-2-thioxothiazolidin-3-yl)pentanoic acids via a Knoevenagel
      condensation were synthesized and evaluated for their antibacterial activity in -
      vitro. The synthesized compounds were characterized by IR, (1)H NMR and MS. The
      antibacterial test in - vitro showed that all of the synthesized compounds had
      good antibacterial activity against several Gram-positive bacteria (including
      multidrug-resistant clinical isolates) with minimum inhibitory concentration
      (MIC) values in the range of 2-4 ug/mL. Especially compounds 4c, 4d, 4e and 4f
      were the most potent, with MIC values of 2 ug/mL against four multidrug-resistant
      Gram-positive bacterial strains. 

PMID- 25561914
TI  - Synthesis and Anticonvulsant Activity Evaluation of 3-alkoxy-4-(4
      (hexyloxy/heptyloxy)phenyl)-4H-1,2,4 -triazole.
AB  - A series of 3-alkoxy-4-(4-(hexyloxy/heptyloxy) phenyl)-4H-1,2,4-triazole was
      synthesized. The anticonvulsant effect and neurotoxicity of the compounds were
      calculated with maximal electroshock (MES) test and rotarod tests with
      intraperitoneally injected mice. Among the synthesized compounds, compound 3
      heptyloxy-4-(4-(hexyloxy) phenyl)-4H-1,2,4-triazole (5f) was the most active one
      and also had the lowest toxicity. In the anti-MES potency test, it showed median
      effective dose (ED50) of 37.3 mg/Kg, median toxicity dose (TD50) of 422.5 mg/Kg,
      and the protective index (PI) of 11.3 which is much greater than the reference
      drug carbamazepine with PI value of 6.4. As well as demonstrating the anti-MES
      efficacy of compound 5f, its potency against seizures induced by
      pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline were also
      established, with the results suggesting that GABA-mediated mechanisms might be
      involved in its anticonvulsant activity, such as enhancing of GABAergic
      neurotransmission or activity, activate GAD or inhibit GABA-T, and GABAA-mediated
      mechanisms. 

PMID- 25561917
TI  - Study on the Interaction between Isatin-beta-Thiosemicarbazone and Calf Thymus
      DNA by Spectroscopic Techniques.
AB  - The interaction between isatin-beta-thiosemicarbazone (IBT) and calf thymus DNA
      (CT-DNA) was investigated in physiological buffer (pH 7.4) using Neutral Red (NR)
      dye as a spectral probe by UV-Vis absorption and fluorescence spectroscopy, as
      well as viscosity measurements. The IBT is stabilized by intercalation in the DNA
      (K [IBT -DNA] = 1.03*10(5) M(-1)), and displaces the NR dye from the NR-DNA
      complex. The binding constants Kf and number of binding sites (n~1) of IBT with
      DNA were obtained by fluorescence quenching method at different temperatures.
      Furthermore, the enthalpy and entropy of the reaction between IBT and CT-DNA
      showed that the reaction is enthalpy-favored and entropy-disfavored. The changes
      in the base stacking of CT-DNA upon the binding of IBT are reflected in the
      circular dichroic (CD) spectral studies. The viscosity increase of CT-DNA
      solution is another evidence to indicate that, IBT is able to be intercalated in
      the DNA base pairs. 

PMID- 25561916
TI  - Synthesis and preliminary evaluation of a new (99m)tc labeled substance p
      analogue as a potential tumor imaging agent.
AB  - Neurokinin 1 receptors (NK1R) are overexpressed on several types of important
      human cancer cells. Substance P (SP) is the most specific endogenous ligand known
      for NK1Rs. Accordingly,a new SP analogue was synthesized and evaluated for
      detection of NK1R positive tumors.[6-hydrazinopyridine-3-carboxylic acid (HYNIC)
      Tyr(8)-Met(O)(11)-SP] was synthesized and radiolabeled with (99m)Tc using
      ethylenediamine-N,N'-diacetic acid (EDDA)and Tricine as coligands. Common
      physicochemical properties of radioconjugate were studied and in-vitro cell line
      biological tests were accomplished to determine the receptor mediated
      characteristics. In-vivo biodistribution in normal and tumor bearingnude mice was
      also assessed. The cold peptide was prepared in high purity (>99%) and
      radiolabeled with (99m)Tc at high specific activities (84-112GBq/umol) with an
      acceptable labeling yield (>95%). The radioconjugate was stable in-vitro in the
      presence of human serum and showed 44% protein binding to human serumalbumin. In
      vitro cell line studies on U373MG cells showed an acceptable uptake up to 4.91 +/
      0.22% with the ratio of 60.21 +/- 1.19% for its specific fraction and increasing
      specific internalization during 4 h. Receptor binding assays on U373MG cells
      indicated a mean Kd of 2.46 +/- 0.43 nM and Bmax of 128925 +/- 8145 sites/cell.
      In-vivo investigations determined the specific tumor uptake in 3.36 percent of
      injected dose per gram (%ID/g) for U373MG cells and noticeable accumulations of
      activity in the intestines and lung. Predominant renal excretion pathway was
      demonstrated. Therefore, this new radiolabeled peptide could be a promising
      radiotracer for detection of NK1R positive primary or secondary tumors. 

PMID- 25561918
TI  - Comparative efficacy of meloxicam and placebo in vasospasm of patients with
      subarachnoid hemorrhage.
AB  - Cerebral vasospasm considered to be a serious cause of morbidity and mortality
      following subarachnoid haemorrhage (SAH).Despite several available therapeutic
      options, current protocols do not prevent major consequences of vasospasm.
      Inflammation is believed to play an important role in post-haemorrhagic
      vasospasm. Meloxicam is a non-steroidal anti-inflammatory drug. The aim of this
      study was to compare the efficacy of meloxicam versus placebo on vasospasm in
      patients with SAH. In this randomized, double-blind, placebo-controlled trial,
      SAH patients randomly received 7.5 mg meloxicam or placebo twice daily for 7
      days. End points were, middle cerebral artery velocity obtained with transcranial
      doppler, in-hospital mortality, hospital stay and discharge Glasgow Outcome
      Scale. Eighty-one patients enrolled in the study. (40 received meloxicam, 41
      received placebo). Baseline characteristics were similar between the groups.
      There were no differences in length of hospitalization (17.4 +/- 3.1 vs 18.6 +/-
      4.2 days; p = 0.145), in-hospital mortality rate (15 vs 22%; p-value=0.569), or
      GOS (p = 0.972) between the two groups. MCA velocity were slightly less in
      patients who had received meloxicam, but not to a significant degree (p-value=0.
      564(. No side effect has been detected for meloxicam. This study did not prove
      meloxicam efficacy in vasospasm of SAH patients. But it demonstrated that
      clinical trial of meloxicam in these patients is feasible and probably safe. The
      effectiveness of meloxicam on cerebral vasospasm has to be studied in larger
      trials. 

PMID- 25561919
TI  - The effects of ginger on fasting blood sugar, hemoglobin a1c, apolipoprotein B,
      apolipoprotein a-I and malondialdehyde in type 2 diabetic patients.
AB  - Diabetes mellitus is the most common endocrine disorder, causes many
      complications such as micro- and macro-vascular diseases. Anti-diabetic,
      hypolipidemic and anti-oxidative properties of ginger have been noticed in
      several researches. The present study was conducted to investigate the effects of
      ginger on fasting blood sugar, Hemoglobin A1c, apolipoprotein B, apolipoprotein A
      I, and malondialdehyde in type 2 diabetic patients. In a randomized, double
      blind, placebo-controlled, clinical trial, a total of 41 type 2 diabetic patients
      randomly were assigned to ginger or placebo groups (22 in ginger group and 19 in
      control group), received 2 g/day of ginger powder supplement or lactose as
      placebo for 12 weeks. The serum concentrations of fasting blood sugar, Hemoglobin
      A1c, apolipoprotein B, apolipoprotein A-I and malondialdehyde were analyzed
      before and after the intervention. Ginger supplementation significantly reduced
      the levels of fasting blood sugar, hemoglobin A1c, apolipoprotein B,
      apolipoprotein B/apolipoprotein A-I and malondialdehyde in ginger group in
      comparison to baseline, as well as control group, while it increased the level of
      apolipoprotein A-I (p<0.05). It seems that oral administration of ginger powder
      supplement can improves fasting blood sugar, hemoglobin A1c, apolipoprotein B,
      apolipoprotein A-I, apolipoprotein B/apolipoprotein A-I and malondialdehyde in
      type 2 diabetic patients. So it may have a role in alleviating the risk of some
      chronic complications of diabetes. 

PMID- 25561920
TI  - In-silico Investigation of Tubulin Binding Modes of a Series of Novel
      Antiproliferative Spiroisoxazoline Compounds Using Docking Studies.
AB  - Interference with microtubule polymerization results in cell cycle arrest leading
      to cell death. Colchicine is a well-known microtubule polymerization inhibitor
      which does so by binding to a specific site on tubulin. A set of 3', 4'-bis
      (substituted phenyl)-4'H-spiro [indene-2, 5'-isoxazol]-1(3H)-one derivatives with
      known antiproliferative activities were evaluated for their tubulin binding
      modes. 3D structures of the derivatives were docked into the colchicine binding
      site of tubulin using GOLD 5.0 program under flexible ligand and semi-flexible
      receptor condition. The spiroisoxazoline derivatives bind tubulin in a similar
      manner to colchicine by establishing at least a hydrogen bonding to Cys(241) as
      well as hydrophobic interactions with Leu(255), Ile(378) and Lys(254) and few
      other residues at the binding pocket. It can be concluded that the
      spiroisoxazoline core structure common to the studied derivatives is a suitable
      scaffold for placing the antitubulin pharmacophoric groups in appropriate spatial
      positions required for tubulin binding activity. 

PMID- 25561922
TI  - The effect of wheat germ extract on premenstrual syndrome symptoms.
AB  - Pre-menstrual syndrome is one of the most common disorders in women and impairs
      work and social relationships. Several treatment modalities have been proposed
      including herbal medicines. Considering the properties of wheat germ, this study
      aimed to determine the effects of wheat germ extract on the symptoms of
      premenstrual syndrome. This triple blind clinical trial was conducted on 84 women
      working in hospitals affiliated to Hamadan University of Medical Sciences.
      Subjects completed daily symptom record form for two consecutive months. After
      definitive diagnosis of premenstrual syndrome, they were randomly divided into
      two groups of 50 people. Then, for two consecutive months, 400 mg capsules of
      wheat germ extract or placebo were used three times a day, from day 16 until day
      5 of the next menstrual cycle. Wheat germ significantly reduced physical symptoms
      (63.56%), psychological symptoms (66.30%), and the general score (64.99%).
      Although the severity of symptoms decreased in both groups, this reduction was
      more significant in the wheat germ extract group (p < 0.001). On the other hand,
      physical symptoms decreased only in the wheat germ extract (p < 0.001) and there
      was no statistically significant difference in the placebo group. No
      complications were observed in any of the groups. It seems that using wheat germ
      extract reduces general, psychological and physical symptoms. 

PMID- 25561921
TI  - Comparison of the Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on
      the Eradication of Helicobacter pylori Infection, Serum Inflammatory Factors and
      Total Antioxidant Capacity.
AB  - Helicobacter pylori infection, the most common chronic bacterial infection in the
      world, and an important cause of gastrointestinal disorders, may be involved in
      the pathogenesis of some extra-gastrointestinal disturbances, as well as an
      increase in blood levels of certain inflammatory markers. Anti-bacterial activity
      against Helicobacter pylori and anti-inflammatory properties of omega-3 fatty
      acids have been studied in several research studies. The purpose of the present
      study was the comparison of the effects of Eicosapentaenoic Acid and
      Docosahexaenoic Acid supplementation on Helicobacter pylori eradication, serum
      levels of some inflammatory markers and total antioxidant capacity. In a
      randomized, double-blind, placebo-controlled clinical trial, 97 Helicobacter
      pylori positive patients (64 patients in the two intervention groups and 33 in
      the control group), received 2 grams daily of Eicosapentaenoic Acid,
      Docosahexaenoic Acid or Medium Chain Triglyceride oil as placebo, along with
      conventional tetra-drug Helicobacter pylori eradication regimen, for 12 weeks.
      Helicobacter pylori eradication test and measurement of concentration of
      interleukine-6, interleukine-8, high-sensitivity C-reactive protein and total
      antioxidant capacity were performed after the intervention. There was no
      significant difference in eradication rate of the infection, levels of
      interleukine-6 and total antioxidant capacity among the three groups, while the
      levels of interleukine-8 and high-sensitivity C-reactive protein were
      statistically different. Eicosapentaenoic Acid or Docosahexaenoic Acid
      supplementation had no significant differential impact on the eradication of
      Helicobacter pylori infection, and serum levels of interleukine-6 and total
      antioxidant capacity. However, it had a desirable effect on the levels of
      interleukine-8 and high-sensitivity C-reactive protein in Helicobacter pylori
      positive patients. 

PMID- 25561923
TI  - A Randomized Placebo-controlled Trial of Clonidine Impact on Sedation of
      Mechanically Ventilated ICU Patients.
AB  - Clonidine has sedative and analgesic properties. Randomized studies examining
      these properties in mechanically ventilated ICU patients are scarce. This study
      was designed to assess the impact of clonidine on sedative agent use in
      mechanically ventilated patients. In a prospective, randomized, double blind,
      placebo-controlled study in a general ICU of a university medical center in
      Tehran, Iran, 40 patients, over 18 years on mechanical ventilation for 3 days or
      more randomized into 2 equal groups of clonidine and placebo. Clonidine arm
      received usual sedation and enteral clonidine 0.1 mg TID and escalated to 0.2 mg
      TID on the second day if hemodynamics remained stable. Ramsay Sedation Score was
      used to assess sedation. Opioids and midazolam were used in all patients. 10
      patients in clonidine and 3 in placebo arms had history of drug abuse (P =
      0.018). The mean of sedatives used in the clonidine/placebo arms (mg/day) were;
      MED (Morphine Equivalent Dose) 91.4 +/- 97.9/112.1 +/- 98.8 P=0.39, midazolam 7.1
      +/- 7.9/8.3 +/- 9.2 P=0.66 and propofol 535.8 +/- 866.7/139.1 +/- 359.9 P=0.125.
      After adjusting for addiction and propofol, clonidine reduced MED use by 79.6
      mg/day (P=0.005) and midazolam by 5.41 mg/day (P = 0.05). Opioids and midazolam
      need reduced by clonidine co-administration regardless of history of drug abuse.
      Acceptable side effect profile and the lower cost of clonidine could make it an
      attractive adjunct to sedative agents in ICU. 

PMID- 25561924
TI  - Effect of Cysteamine on Cell Growth and IgG4 Production in Recombinant Sp2.0
      Cells.
AB  - The manipulation of redox potential in secretory pathway by thiol reducing agents
      can be a strategy to improve the production levels of disulfide-bonded proteins
      including recombinant antibodies. Here we have studied the influence of
      cysteamine on viability and the production level of IgG4 in Sp2.0 cells. For this
      purpose, the recombinant Sp2.0 cells producing an anti CD33 IgG4, were subjected
      to different concentrations of cysteamine. At concentrations of 2, 4 and 5 mM
      cysteamine, the secreted levels of IgG4 did not change significantly. However, in
      concentration of 7 mM cysteamine, a significant decrease was observed in IgG4
      levels which may indicate the cytotoxicity of this compound in higher
      concentrations. Our results show that the cysteamine treatment reduces the cell
      viability in a dose-dependent manner. Also it was observed that 2 mM cysteamine
      had no late effect on IgG4 production level and only at day 3, this concentration
      of cysteamine decreased the cell viability significantly. To test whether the
      addition of cysteamine can affect the expression level of protein disulfide
      isomerase, RT-PCR analysis was carried out. The results revealed that cysteamine
      does not affect the PDI transcription and expression level of IgG4 in this type
      of recombinant cells. 

PMID- 25561925
TI  - Cloning and Expression of TNF Related Apoptosis Inducing Ligand in Nicotiana
      tabacum.
AB  - Molecular farming has been considered as a secure and economical approach for
      production of biopharmaceuticals. Human TNF Related Apoptosis Inducing Ligand
      (TRAIL) as a promising biopharmaceutical candidate has been produced in different
      expression hosts. However, little attention has been paid to molecular farming of
      the TRAIL in spite of numerous advantages of plant expression systems. Therefore,
      in this study the cytoplasmic production of the TRAIL was tackled in Nicotiana
      tabacum using Agrobacterium tumefaciens LBA 4404. Initially, the desired coding
      sequence was obtained using PCR technique on the constructed human cDNA library.
      Afterward, the necessary requirements for expression of the TRAIL in plant cell
      system were provided through sub-cloning into 35S-CaMV (Cauliflower Mosaic Virus)
      helper and final 0179-pGreen expression vectors. Then, the final TRAIL-pGreen
      expression vector was cloned into A. tumefaciens LBA 4404. Subsequently, the N.
      tabacum cells were transformed through co-culture method and expression of the
      TRAIL was confirmed by western blot analysis. Finally, the recombinant TRAIL was
      extracted through chromatographic technique and biological activity was evaluated
      through MTT assay (Methylthiazol Tetrazolium Assay). The result of western blot
      analysis indicated that only monomer and oxidized dimer forms of the TRAIL can be
      extracted from the N. tabacum cells. Moreover, the lack of trimeric assembly of
      the extracted TRAIL diminished its biological activity in sensitive A549 cell
      line. In conclusion, although N. tabacum cells can successfully produce the
      TRAIL, proper assembly and functionality of the TRAIL were unfavorable. 

PMID- 25561926
TI  - In-silico Metabolome Target Analysis Towards PanC-based Antimycobacterial Agent
      Discovery.
AB  - Mycobacterium tuberculosis, the main cause of tuberculosis (TB), has still
      remained a global health crisis especially in developing countries. Tuberculosis
      treatment is a laborious and lengthy process with high risk of noncompliance,
      cytotoxicity adverse events and drug resistance in patient. Recently, there has
      been an alarming rise of drug resistant in TB. In this regard, it is an unmet
      need to develop novel antitubercular medicines that target new or more effective
      biochemical pathways to prevent drug resistant Mycobacterium. Integrated study of
      metabolic pathways through in-silico approach played a key role in
      antimycobacterial design process in this study. Our results suggest that
      pantothenate synthetase (PanC), anthranilate phosphoribosyl transferase (TrpD)
      and 3-isopropylmalate dehydratase (LeuD) might be appropriate drug targets. In
      the next step, in-silico ligand analysis was used for more detailed study of
      chemical tractability of targets. This was helpful to identify pantothenate
      synthetase (PanC, Rv3602c) as the best target for antimycobacterial design
      procedure. Virtual library screening on the best ligand of PanC was then
      performed for inhibitory ligand design. At the end, five chemical intermediates
      showed significant inhibition of Mycobacterium bovis with good selectivity
      indices (SI) >=10 according to Tuberculosis Antimicrobial Acquisition &
      Coordinating Facility of US criteria for antimycobacterial screening programs. 

PMID- 25561928
TI  - Antimicrobial Activities of Three Medicinal Plants and Investigation of
      Flavonoids of Tripleurospermum disciforme.
AB  - Rosa damascena, Tripleurospermum disciforme and Securigera securidaca were used
      as disinfectant agents and for treatment of some disease in folk medicine of
      Iran. The antimicrobial effects of different fractions of seeds extract of S.
      securidaca, petals extract of R. damascena and aerial parts extract of T.
      disciforme were examined against some gram positive, gram negative and fungi by
      cup plate diffusion method. The petroleum ether and chloroform fractions of S.
      securidaca showed antibacterial activities against Staphylococcus aureus and
      Pseudomonas aeruginosa, while its methanol fraction had no antibacterial effects.
      R. damascena petals extract demonstrated antibacterial activities against
      Bacillus cereus, Staphylococcus epidermidis, S. aureus and Pseudomonas
      aeruginosa. T. disciforme aerial parts extract exhibited antimicrobial effects
      only against S. aureus and S. epidermidis. None of the fractions had any
      antifungal activities. Therefore, present study confirmed utility of these plants
      as disinfectant agents. Six flavonoids were isolated from T. disciforme:
      Luteolin, Quercetin-7-O-glucoside, Kaempferol, Kaempferol-7-O-glucoside, Apigenin
      and Apigenin-7-O-glucoside. The flavonoids and the antimicrobial activity of T.
      disciforme are reported for the first time. 

PMID- 25561927
TI  - Biological Activity and Phytochemical Study of Scutellaria platystegia.
AB  - This study aimed to determine biological activity and phytochemical study of
      Scutellaria platystegia (family Labiatae). Methanolic (MeOH) extract of aerial
      parts of S. platystegia and SPE fractions of methanolic extract (specially 20%
      and 40% methanolic fractions), growing in East-Azarbaijan province of Iran were
      found to have radical scavenging activity by DPPH (2, 2-diphenyl -1- pycryl
      hydrazyl) assay. Dichloromethane (DCM) extract of this plant exhibited
      animalarial activity by cell free method providing IC50 at 1.1876 mg/mL. Crude
      extracts did not exhibit any toxicity assessed by brine shrimp lethality assay.
      Phytochemical study of methanolic extract by using reverse phase HPLC method and
      NMR instrument for isolation and identification of pure compounds respectively,
      yielded 2-(4- hydroxy phenyl) ethyl-O-beta-D- glucopyranoside from 10% and
      apigenin 7-O-glucoside, verbascoside and martynoside from 40% SPE fraction.
      Occurance of verbascoside and martynoside as biochemical markers appeared to be
      widespread in this genus. Antioxidant and antimalarial activity of MeOH and DCM
      extracts, respectively, as well as no general toxicity of them could provide a
      basis for further in-vitro and in-vivo studies and clinical trials to develop new
      therapeutical alternatives. 

PMID- 25561929
TI  - Fatty Acid and Essential Oil Compositions of Trifolium angustifolium var.
      angustifolium with Antioxidant, Anticholinesterase and Antimicrobial Activities.
AB  - This study represents the first report on the chemical composition and biological
      activity of Trifolium angustifolium var. angustifolium. The major components of
      the essential oil were identified as hexatriacontene (23.0%), arachidic acid
      (15.5%) and alpha-selinene (10.0%). The main constituents of the fatty acid
      obtained from the petroleum ether extract were identified as palmitic acid
      (29.8%), linoleic acid (18.6%) and oleic acid (10.5%). In particular, the water
      extract exhibited higher activity than alpha-tocopherol and BHT, which were used
      as standards in the ABTS cation radical scavenging assay and indicated higher
      inhibitory effect against acetylcholinesterase enzyme than the reference
      compound, galanthamine but exhibited weak activity in beta-carotene bleaching,
      DPPH-free radical scavenging, and cupric-reducing antioxidant capacity assays.
      The petroleum ether extract exhibited higher activity than alpha-tocopherol which
      was used as standard in the beta-carotene bleaching method at concentration 100
      MUg/mL. The acetone extract exhibited higher activity than alpha-tocopherol which
      was used as standard cupric reducing antioxidant capacity (CUPRAC) method at 100
      MUg/mL concentration. The acetone and methanol extracts were active on all
      microorganisms tested with a small zone diameter indicating weak activity. 

PMID- 25561930
TI  - Phytochemical Investigation on Euphorbia macrostegia (Persian wood spurge).
AB  - Euphorbia macrostegia or Persian wood spurge is one of the seventeen endemic
      plants of this genus in Iran. Three triterpenoids, 24-methylenecycloartan-3beta
      ol (1), butyrospermol (2) and cycloartenol (3) and three diglycerides, 1,2-di-O
      alpha-linolenoyl-sn-glycerol (4), 1-O-linoleoyl-3-O-palmitoyl-sn-glycerol (5) and
      1-O-alpha-linolenoyl-2-O-palmitoyl-sn-glycerol (6) were isolated from the hexane
      soluble part of methanol-dichloromethane extracts of the aerial parts of
      Euphorbia macrostegia Boiss. The structures of all compounds were elucidated
      using different spectroscopy methods including, (1)H NMR, (13)C NMR, HSQC, HMBC,
      EI-MS and IR. The triterpenes and the unsaturated fatty acids moieties of the
      diglycerides isolated from the plant were reported previously to have analgesic,
      anticancer, bactericidal and antifungal activity. Here, we show that E.
      macrostegia is a new source for the above mentioned biologically active
      compounds. 

PMID- 25561931
TI  - Effects and Mechanism of Baicalin on Apoptosis of Cervical Cancer HeLa Cells I n 
      v itro.
AB  - The objective of this study was to observe the apoptosis-inducing effect and
      mechanism of baicalin on human cervical cancer HeLa cells. The inhibitory effect
      of baicalin on the growth of HeLa cells was measured by MTT assay, and cell
      proliferation and migration was analyzed by cell scratch assay. Morphological
      changes of apoptotic cells were viewed by the light microscope and electron
      microscope, and cell growth arrest was confirmed by flow cytometry. Moreover,
      Western blot was used for investigating the expression of apoptosis related
      proteins; spectrophotometry was used to examine Caspase-3 activation. Our results
      showed that baicalin could inhibit the proliferation of HeLa Cells via induction
      of apoptosis in a time and dose-dependent manner (P<0.01). Apoptotic signaling
      induced by baicalin was characterized by up-regulating Bax, Fas, FasL and Caspase
      8 protein expression, and down-regulating of Bcl-2 protein expression. These
      results indicated that baicalin-induced apoptosis involved activation Caspase-3
      in HeLa cells through the intracellular mitochondrial pathway and the surface
      death receptor pathway. 

PMID- 25561932
TI  - Evaluation of Anti-inflammatory and Analgesic Activity of the Extract and
      Fractions of Astragalus hamosus in Animal Models.
AB  - The objective of this study was to evaluate the anti-inflammatory and analgesic
      activities of the hydro-alcoholic extract of the pods of Astragalus hamosus
      (HAAH), a plant used in Iranian traditional medicine, and antinociceptive effects
      of different fractions in animal models. The anti-inflammatory effect was
      evaluated by the rat paw edema induced by formalin. Also the analgesic effect was
      examined by the acetic-acid-induced writhing response and hot plate test. The
      analgesic effects of chloroform, hexane, ethyl acetate and aqueous fractions were
      evaluated by the hot-plate method. The hydroalcoholic extract of Astragalus
      hamosus could reduce the edema in a dose-dependent manner (P<0.05). In the acute
      phase, the result of 1000 mg/Kg and in the chronic phase, the result of 100 and
      300 mg/Kg of the extract were more significant and comparable with the effect of
      sodium salicylate. Also application of different doses of HAAH had significant
      anti-nociceptive effects on both animal models. The findings showed that HAAH at
      doses of 700 and 1000 mg/Kg produced analgesic effects comparable to sodium
      salicylate. The hexane and ethyl acetate (but not the other fractions) showed
      significant analgesic activity in hot plate test, when compared to morphine. The
      results of this study demonstrated the anti-inflammatory and analgesic effects of
      HAAH extract and hexane and ethyl acetate fractions of the extract in animal
      models and justify traditional use of this plant in the treatment of pain and
      inflammatory conditions. More studies to clarify the active components are
      necessary. 

PMID- 25561933
TI  - A comparison of toxicity mechanisms of cigarette smoke on isolated mitochondria
      obtained from rat liver and skin.
AB  - Previous studies demonstrated that CSE induces oxidative stress and its
      consequences on isolated mitochondria obtained from lung, heart and brain which
      may provide insight into the role of CSE in human health and disease. The present
      study was carried out to further characterize and compare toxic effect of CSE
      extract on isolated mitochondria obtained from either a directly contacting
      tissue (i.e. skin) or a vital visceral tissue (i.e. liver).We obtained Rat liver
      and skin mitochondria by differential ultracentrifugation and incubated the
      isolated mitochondria with different concentrations (1, 10 and 100%)
      ofstandardizedcigarette smoke extract (CSE). Our results were similar to our
      previous study which discovered CSE toxicity mechanisms on isolated mitochondria
      obtained from lung, heart and brain with minor changes.CSE induced a significant
      rise in ROS formation, lipid peroxidation and mitochondrial membrane potential
      collapse and mitochondrial swelling on isolated mitochondria obtained from both
      liver and skin. CSE induced Decrease in ATP concentration on isolated
      mitochondria obtained from both liver and skin did not include CSE lowest
      concentration (1%). Our findingsshowed that CSE-induced toxicity in liver and
      skin is due to disruptive effect on mitochondrial respiratory chain which
      canleads to cytochrome c release and apoptosis signaling. 

PMID- 25561934
TI  - Cardioprotective Effects of Essential Oil of Lavandula angustifolia on
      Isoproterenol-induced Acute Myocardial Infarction in Rat.
AB  - Myocardial infarction (MI) is a common presentation of the ischemic heart
      disease. Lavandula angustifolia is an herbaceous plant with antioxidative
      effects. This study was designed to investigate the cardioprotective effects of
      lavandula angustifolia essential oil against isoproterenol-induced MI in rats.
      The dried sample was subjected to hydrodistillation by using a Clevenger and the
      oils were dried over anhydrous Na2SO4. Male Wistar rats were assigned to 6 groups
      of control, sham, isoproterenol and treatment with 5, 10, 20 mg/Kg of the
      essential oil. MI was induced by subcutaneous injection of Isoproterenol (100
      mg/Kg) for 3 consecutive days at an interval of 24 h. The essential oil was given
      intraperitoneally every 24 h started at MI induction. Following anesthesia,
      hemodynamic parameters were measured. After sacrificing the animals, the hearts
      were removed to measure the heart to body weight ratio and histopathological
      examination. Myeloperoxidase (MPO) and Malondialdehyde (MDA) were measured in
      heart tissues for evaluating the activity of neutrophils and lipid peroxidation,
      respectively. The essential oil amended ECG pattern by suppressing ST-segment
      elevation and increasing R-amplitude. 10 mg/Kg of the essential oil significantly
      decreased heart to body weight ratio (P<0.001) and the elevation of MDA and MPO
      in myocardium, it also increased dp/dtmax from 2793 +/- 210 to 4488 +/- 253
      mmHg/sec (P<0.001), and 20 mg/Kg of it significantly lowered LVEDP from 14 +/-
      3.43 to 4.3 +/- 0.83 mmHg (P<0.001).The results demonstrated that L. angustifolia
      protects myocardium against isoproterenol-induced MI that it could be related to
      its antioxidant properties. 

PMID- 25561935
TI  - Protein Drug Targets of Lavandula angustifolia on treatment of Rat Alzheimer's
      Disease.
AB  - Different treatment strategies of Alzheimer's disease (AD) are being studied for
      treating or slowing the progression of AD. Many pharmaceutically important
      regulation systems operate through proteins as drug targets. Here, we investigate
      the drug target proteins in beta-amyloid (Abeta) injected rat hippocampus treated
      with Lavandula angustifolia (LA) by proteomics techniques. The reported study
      showed that lavender extract (LE) improves the spatial performance in AD animal
      model by diminishing Abeta production in histopathology of hippocampus, so in
      this study neuroprotective proteins expressed in Abeta injected rats treated with
      LE were scrutinized. Rats were divided into three groups including normal, Abeta
      injected, and Abeta injected that was treated with LE. Protein expression
      profiles of hippocampus tissue were determined by two-dimensional electrophoresis
      (2DE) method and dysregulated proteins such as Snca, NF-L, Hspa5, Prdx2, Apoa1,
      and Atp5a1were identified by MALDI-TOF/TOF. KEGG pathway and gene ontology (GO)
      categories were used by searching DAVID Bioinformatics Resources. All detected
      protein spots were used to determine predictedinteractions with other proteins in
      STRING online database. Different isoforms of important protein, Snca that
      exhibited neuroprotective effects by anti-apoptotic properties were expressed. NF
      L involved in the maintenance of neuronal caliber. Hspa5 likewise Prdx2 displays
      as anti-apoptotic protein that Prdx2 also involved in the neurotrophic effects.
      Apoa1 has anti-inflammatory activity and Atp5a1, produces ATP from ADP. To sum
      up, these proteins as potential drug targets were expressed in hippocampus in
      response to effective components in LA may have therapeutic properties for the
      treatment of AD and other neurodegenerative diseases. 

PMID- 25561936
TI  - Time dependent antinociceptive effects of morphine and tramadol in the hot plate
      test: using different methods of drug administration in female rats.
AB  - Morphine and tramadol which have analgesic effects can be administered acutely or
      chronically. This study tried to investigate the effect of these drugs at various
      times by using different methods of administration (intraperitoneal, oral, acute
      and chronic). Sixty adult female rats were divided into six groups. They received
      saline, morphine or tramadol (20 to 125 mg/Kg) daily for 15 days. A hot plate
      test was performed for the rats at the 1(st), 8(th) and 15(th) days. After drug
      withdrawal, the hot plate test was repeated at the 17(th), 19(th), and 22(nd)
      days. There was a significant correlation between the day, drug, group, and their
      interaction (P<0.001). At 1(st) day (d1), both morphine, and tramadol caused an
      increase in the hot plate time comparing to the saline groups (P<0.001), while
      there was no correlation between drug administration methods of morphine and/or
      tramadol. At the 8(th) day (d8), morphine and tramadol led to the most powerful
      analgesic effect comparing to the other experimental days (P<0.001). At the
      15(th) day (d15), their effects diminished comparing to the d8. After drug
      withdrawal, analgesic effect of morphine, and tramadol disappeared. It can be
      concluded that the analgesic effect of morphine and tramadol increases with the
      repeated use of them. Thereafter, it may gradually decrease and reach to a level
      compatible to d1. The present data also indicated that although the analgesic
      effect of morphine and tramadol is dose-and-time dependent, but chronic exposure
      to them may not lead to altered nociceptive responses later in life. 

PMID- 25561937
TI  - Immunomodulatory effects of bee venom in human synovial fibroblast cell line.
AB  - As in Iranian traditional medicine, bee venom (BV) is a promising treatment for
      the rheumatoid arthritis (RA) which is considered as a problematic human chronic
      inflammatory disease in the present time. Smoking is considered to be a major
      risk factor in RA onset and severity. The main aim of this study is to
      investigate the effects of BV on cigarette smoke-induced inflammatory response in
      fibroblast-like synoviocytes (FLS). Cytotoxicity of cigarette smoke condensate
      (CSC) and bee venom were determined by the tetrazolium (MTT) method in cultured
      synovial fibroblastes. The expression of interleukin-1beta and sirtuin1 mRNA were
      analyzed by SYBR green real-time quantitative PCR. Differences between the mean
      values of treated and untreated groups were assessed by student t-test. Based on
      MTT assay, CSC and BV did not exert any significant cytotoxic effects up to 40
      ug/mL and 10 ug/mL, respectively. Our results showed that interleukin-1beta mRNA
      level was significantly up-regulated by CSC treatments in LPS-stimulated
      synoviocytes in a dose-dependent manner. Conversely, the expressions of IL-1beta
      and Sirt1 were up-regulated even in lower concentrations of BV and attenuated at
      higher concentrations. Also, BV attenuated the CSC-induced and LPS-induced
      inflammatory responses in synovial fibroblasts. Our results support the
      epidemiological studies indicating pro-inflammatory effects of CSC and anti
      inflammatory effects of BV on FLS cell line. 

PMID- 25561938
TI  - Variations in Intraplatelet Phospho-VASP Expression Due to Pre-analytical Sample
      Preparations, Illustration of a Quality Control Issue in Platelet Pharmacology.
AB  - Intraplatelet vasodilator-stimulated phosphoprotein (VASP) analysis is a commonly
      used laboratory approach for monitoring of the anti-platelet therapy with
      adenosine diphosphate (ADP) receptor blocking agents; however, it's testing in
      clinical laboratory needs a high level of experience and proficiency. The ability
      to recognize how the pre-analytical variations can change the results would be
      helpful for the interpretation of data from intraplatelet VASP analysis. The aim
      of this study was to describe the possible differences of intraplatelet phospho
      VASP expression between washed and platelet rich plasma (PRP) samples, both at
      baseline levels and following experimentally induction of VASP phosphorylation.
      PRP and washed platelet samples were treated with different inducers of VASP
      phosphorylation, including forskolin (10 uM), prostaglandin E1 (PGE1) (50 nM) and
      sodium nitro-prusside (SNP) (100 uM). Untreated PRP and washed platelet samples
      were also included in study as baseline controls. After labeling of platelets
      with either anti P-Serine(157)-VASP or anti P-Serine(239)-VASP, the samples were
      subjected to flow cytometric analysis to monitor the levels of intraplatelet
      phospho-VASP expression. Washed platelet samples tend to show increased
      expression of intraplatelet P-Serine(157)-VASP at baseline state and also more
      expression of P-Serine(157)-VASP and P-Serine(239)-VASP in response to forskolin
      and SNP, compared with PRP samples. Though, reduced levels of PGE1-induced VASP
      phosphorylation at both residues were detected for washed platelets. In this
      study we have provided some background information required for performing of
      intraplatelet VASP analysis on differently handled platelet samples and
      interpretation of the obtained results. 

PMID- 25561939
TI  - Grape Seed Proanthocyanidin Extract Improved some of Biochemical Parameters and
      Antioxidant Disturbances of Red Blood Cells in Diabetic Rats.
AB  - Grape seed proanthocyanidin extract (GSPE) has a broad spectrum of biologic
      properties against oxidative stress. This study aimed to investigate the effects
      of GSPE on biochemical factors and antioxidant enzymes of erythrocyte in diabetic
      rats. Diabetes was induced through single injection of streptozotocin (50 mg.Kg(
      1), i.p). Forty Male Sprague-Dawley rats were divided into four Groups: Group 1,
      healthy control group; Group 2, healthy group treated with GSPE (200 mg.Kg(-1));
      Group 3, diabetic control group; Group 4, diabetic group treated with GSPE (200
      mg.Kg(-1)) for 4 weeks. At the end, the experimental animals were sacrificed and
      blood samples were collected and plasma parameters and erythrocytes antioxidant
      status were evaluated. The results show, treatment with GSPE significantly
      reduced (P<0.001) urine volume, proteinuria and biochemical factors such as blood
      urea nitrogen, creatinine, triglyceride, total cholesterol, low density
      lipoprotein and very low density lipoprotein as well as malondialdehyde. Also
      GSPE treatment significantly (P<0.005) increased high density lipoprotein, total
      protein and albumin. Moreover GSPE significantly increased antioxidant enzymes
      activity such as: superoxide dismutase, glutathione peroxidase and catalase.
      These results suggest that GSPE can ameliorate biochemical abnormalities and
      antioxidant system status in streptozotocin- induced diabetic rats probably by
      its potent antioxidant features. 

PMID- 25561940
TI  - Preventive Effects of Aqueous Extract of Berberis integerrima Bge. Root on Liver
      Injury Induced by Diabetes Mellitus (Type 1) in Rats.
AB  - This study was conducted to assessthe preventive effect of aqueous extract of
      Berberis integerrima Bge. root (AEBIR) on liver damage and oxidative stress
      induced by diabetes mellitus in rats. Forty male rats were divided into 5 groups
      as follows: 1- normal (N); 2- normal + barberry (N+B) (they received barberry
      root extract for 6 weeks); 3- diabetic (D) (they received Streptozotocin (STZ),
      65 mg/Kg BW /i.p.); 4- diabetic +barberry before (D+Bb) (they received barberry
      root extract for 3 weeks before STZ injection and continued for another three
      weeks); and 5- diabetic + barberry after (D+Ba) (three days after STZ injection,
      they received barberry root extract for 3 weeks). The experimental groups
      received barberry root extract (500 mg/Kg bw) intra gastric by gavage for 6
      weeks. The treatment of diabetic rats with AEBIR showed a significant
      decreases(p<0.001) in levels of blood glucose, malondialdehyde (MDA), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase
      (ALP) and total bilirubin while body weight, total protein, superoxide dismutase
      (SOD), catalase(CAT) and reduced glutathione (GSH) increased (p<0.001) in
      comparison to diabetic control rats. Consumption of AEBIR in group D+Bb caused
      significant improvement in all these factors, compared to the group D+Ba. Also in
      this study, for the first time, we demonstrated that administration of AEBIR
      before diabetes induction resulted in enhanced amelioration of liver
      complications compared to the group receiving it after induction, indicating that
      AEBIR can play a preventive role in such patients. 

PMID- 25561941
TI  - Mental Health Changes and Its Predictors in Adolescents using the Path Analytic
      Model: A 7-Year Observational Study.
AB  - OBJECTIVE: This 7-year observational study examines the hours of TV-watching,
      phone conversation with friends, using the internet, and physical activity as
      predictors of mental health among adolescents in south of Iran. METHODS: At the
      baseline (in 2005), the participants were 2584 high school students in the 9th to
      11th grade. At the baseline, 30% of the available participants (n = 775) were
      selected in the follow-up (2012) using convenience sampling method. This study
      used the path analysis to examine the predictors of mental health and to obtain
      direct, indirect and total effects of the independent variables. RESULTS: At the
      baseline (2005), female gender, internet use, maternal education, physical
      activity and father's education were associated with mental health (p<0.05).
      Baseline mental health, internet use and physical activity predicted mental
      health of the participants in the follow up (p<0.05). CONCLUSION: The findings of
      the study revealed that better mental health in later life is associated with
      better mental health at baseline, male gender, higher physical activity and phone
      communication with friends, and less use of the internet and TV.

PMID- 25561942
TI  - Patients' preference to hear cancer diagnosis.
AB  - OBJECTIVE: Bad news disclosure is one of the complex communication tasks of the
      physicians. Bad news is defined as:" any news that adversely and seriously
      affects an individual's view of his or her future". Recent studies indicate that
      the patients' and physicians' attitudes toward disclosure of bad news have been
      changed since few years ago. The evidence of breaking bad news is also different
      across different cultures. In the present study, we aimed to evaluate the
      patients' prospect about breaking bad news and to provide a clinical guidance for
      Iranian patients and those patients in countries with a similar cultural
      background. METHODS: A cross sectional descriptive study was conducted on a
      sample of 200 cancer patients at a cancer institute in Tehran. The patients'
      demographic characteristics and their attitudes toward the manner of disclosing
      the diagnosis were registered in a research based questionnaire. RESULTS: In this
      study, 165 patients (82.5%) claimed to be aware of the diagnosis; however, only
      121 patients (73%) were aware of the actual diagnosis of their disease. Most
      patients tended to know the diagnosis (n = 186, 93%) and accepted patient as the
      first person to be informed (n = 151, 75.5%) by their physician (n = 174, 87%).
      The preference of being alone or with a family member when exposed to bad news
      was almost the same. Most patients (n = 169, 84.5%) believed that physicians
      should consult the patients to make treatment decisions. Treatment options (n =
      140, 70%) and life expectancy (n = 121, 60.5%) were the most desirable topics to
      be discussed. Most patients (n = 144, 72%) agreed upon allowing them to express
      their emotional feelings. CONCLUSION: According to the patients' preferences
      about being fully informed about the diagnosis, it is suggested that the
      disclosure of cancer diagnosis be done by a physician and in the presence of a
      family member. It is also recommended that physicians consult the patients about
      treatment options.

PMID- 25561943
TI  - Juvenile Myoclonic Epilepsy (JME): Neuropsychological Profile and Related Factors
      with Cognitive Dysfunction.
AB  - OBJECTIVE: The aim of present study was to verify possible cognitive dysfunction
      in the patients with Juvenile Myoclonic Epilepsy (JME) and its correlation to
      factors related to epilepsy and patients demographic variables. MATERIAL AND
      METHODS: Thirty two consecutive patients with JME and 32 healthy controls were
      evaluated in neuropsychological domains including orientation, mental control,
      logical memory, forward and backward digit spans, visual memory, associative
      learning, and memory quotient (using Persian version of Wechsler Memory Scale
      (WMS)-Revised), preservative errors (using Wisconsin Card Sorting Test (WCST)),
      Stroop Test (color and word), IQ score (using Raven's Progressive Matrices test),
      and depression (using the Persian version of Beck Depression Inventory (BDI)).
      SPSS 11.0 (SPSS Inc., Chicago, Illinois, USA) software was used for statistical
      analysis. Student's t-test and the Mann-Whitney U-test were used for independent
      normally and non-normally distributed continuous variables, respectively.
      RESULTS: Our study showed significant differences between patients with JME and
      control group with respect to scores of mental control (p=0.015), forward digit
      span (p=0.004), total digit span (p=0.008) and IQ (p=0.003). In addition, age,
      education level, duration of epilepsy and medication showed an impact on several
      cognitive functions in the patients with JME. CONCLUSION: It is indicated that
      JME is associated with impairment in specific cognitive domains, despite any
      evidence in favor of depression.

PMID- 25561944
TI  - Facial emotion recognition in adolescents with bipolar disorder.
AB  - OBJECT: Bipolar disorder (BD) is associated with abnormalities in emotional
      competence. One of the main aspects of this competency is emotion recognition
      which is presented in the face. This study aimed to evaluate facial emotion
      recognition in adolescents with bipolar disorder when they are free of acute
      symptoms. METHOD: Thirty patients diagnosed with BD aged 12 to 18 were selected
      from a large sample of consecutive admitted adolescents in Roozbeh hospital. They
      were compared with 30 matched normal developing adolescents who were recruited
      from mainstream schools at Tehran. All participants were evaluated using a facial
      emotion recognition task. The participants needed to recognize happy, sad, angry
      and neutral facial expressions The ANOVA was used to analyze the differences
      between the two groups in terms of emotion recognition variables. RESULTS: The
      patients with BD showed a significant deficit in recognizing emotions in general
      (p=.01) which was prominent in the angry faces. Their response time to recognize
      the facial expressions was longer compared to the normal individuals. This
      difference was significant in recognizing the happy and neutral faces (p<0.05).
      CONCLUSION: This study suggests an inaccurate recognition of facial expressions
      in adolescents with BD, particularly for anger, as well as slowness in detecting
      emotions especially happiness.

PMID- 25561945
TI  - A comparison of effectiveness of regulation of working memory function and
      methylphenidate on remediation of attention deficit hyperactivity disorder
      (ADHD).
AB  - Attention Deficit/Hyperactivity Disorder (ADHD) is a prevalent and serious
      disorder affecting such key cognitive components as working memory. Working
      memory serves to facilitate and check attention in any individual and to focus on
      those affairs that need to be retained in mind. This study examines whether a
      combination of the two therapeutic methods of working memory training and
      Methylphenidate might be more effective in treating ADHD in children aged 6 to 12
      years of age than when methylphenidate is applied alone. METHOD: Subjects of the
      study are 48 children suffering from ADHD. They were selected by random sampling.
      The experimental group included 23 children with ADHD who received a combination
      of working memory training and Methylphenidate, and the control group which
      included 25 children with ADHD received Methylphenidate only. To check the
      effects of the intervention, Conners' Parent Rating Scale (CPRS-48) was applied
      before and after the intervention. After intervention, data were collected from
      the remaining samples in the two groups. Data were examined both through
      descriptive statistical methods and analytic statistical methods, including T
      student test and Quantile-Quantile Plots diagram. RESULTS: The study demonstrated
      that a combination of the cognitive intervention of working memory training and
      methylphenidate is more effective in alleviating ADHD symptoms rather than when
      methylphenidate is applied in isolation. In the CPRS pre-test and post-test, the
      mean difference of the experimental and the control group was 8.39 and 1.88
      respectively, indicating that the working memory group has improved more than the
      control group. CONCLUSIONS: The study reveals that the ADHD symptoms were more
      contained in the test group than the control group due to working memory
      training. The cognitive intervention through working memory training may be
      effective in alleviating the severity of disorder measured in the pre-test.

PMID- 25561946
TI  - Iranian mothers' perception of the psychological birth trauma: A qualitative
      study.
AB  - OBJECTIVE: Childbirth is one of the most vulnerable moments and the most
      important and memorable events in the lives of women that despite of bringing
      happiness, it can be associated with psychological trauma and endanger the mother
      and neonate health. Mothers' perception of the psychological birth trauma is a
      highly subjective process that depends on the cultural, social and biological
      conditions of mothers that is not achievable except with examination of their
      views. This study aimed to understand psychological birth trauma from the
      perceptions of Iranian mothers. METHODS: A qualitative research design using in
      depth interviews of 23 Iranian mothers was conducted from Tehran and Isfahan
      health centers. The interviews were transcribed and analyzed using conventional
      content analysis. RESULTS: Two themes were extracted from the data: impact of
      psychological birth trauma and trends of psychological birth trauma. Several
      categories and sub-categories also emerged from the data. Feelings of fear,
      anxiety, helplessness and sense of impending death (collapse) were reported by
      the mothers. CONCLUSIONS: By considering the unforgettable experience of mothers
      from the psychological birth trauma, a plan for supportive care before, during
      and after birth is critical.

PMID- 25561947
TI  - The Relationship between Major Depressive Disorder and Personality Traits.
AB  - OBJECTIVE: The aim of this study was to compare the clinical temperaments and
      characters of Iranian patients with Major Depressive Disorder (MDD) with healthy
      controls. METHOD: The study participants included 47 outpatients with Major
      Depressive Disorder (MDD) and 120 normal controls with no psychiatric disorders.
      Sampling method was convenience. The MDD patients were diagnosed as MDD by a
      psychiatrist using the Persian structured clinical interview for axis I disorders
      (SCID-I), and they completed at least 8 weeks of antidepressant treatment. All
      the patients filled out the Persian version of the Temperament and Character
      Inventory (TCI). Data were analyzed using SPSS version 17, Chi square, T test and
      Multiple Regression. The level of significance was set at 5%. RESULTS: The
      present study demonstrates a link between depression and lower persistence
      (p<=0.001), self-directedness (p<=0.001) and cooperativeness (p<=0.001) scores. A
      negative correlation between age and Harm Avoidance (p<=0.001) was observed in
      both groups. CONCLUSION: Lower scores of persistence (P), self-directedness (SD)
      and cooperativeness (CO) were observed in patients with depression more than
      controls even in the remission phase which could indicate a relationship between
      these traits and depression.

PMID- 25561948
TI  - Dyke-Davidoff-Masson Syndrome- a rare cause of refractory epilepsy.
AB  - Dyke-Davidoff-Masson Syndrome (DDMS) is a syndrome associated with refractory
      epilepsy. DDMS is a rare syndrome characterized by seizures, facial asymmetry,
      contralateral hemiplegia and mental retardation. The characteristic radiologic
      features are cerebral hemiatrophy with homolateral hypertrophy of the skull and
      sinuses. The case was an 18 years old female with seizures, hemiparesis of the
      right side and mental retardation who was diagnosed with DDMS based on computed
      tomography. 

PMID- 25561949
TI  - A case of Ventricular Tachycardia and Cardiac Arrest Associated with Sertraline
      and Mirtazapine Combination.
AB  - A 67-year-old male suffering from depressive symptomatology was admitted to the
      inpatient clinic at Firat University School of Medicine; and his psychiatric
      evaluation revealed major depressive episode according to DSM-IV. He developed
      chest discomfort, chest pain and shortness of breath of acute onset accompanying
      pulseless ventricular tachycardia (VT) leading to cardiac arrest following
      sertraline and mirtazapine combination treatment. He died after two days in the
      Intensive Care Unit. The present case suggests that psychiatrists should be aware
      of unexpected cardiac events, especially when they use combination treatments. 

PMID- 25561950
TI  - Child Abuse in Iran: a systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of the present study was to estimate the pooled prevalence of
      different types of child abuse in Iran. METHOD: We systematically searched four
      English databases (PubMed, Sciencedirect, PsychINFO and Scopus), and three Farsi
      databases (Magiran, IranMedex and SID) to find out relevant articles that have
      reported the prevalence of child abuse in Iran. Studies conducted on special
      samples, special setting or on adult population for history of child abuse were
      excluded from our study. The total number of obtained articles from English
      databases was 83. After removing the duplicated articles, 77 manuscripts
      remained. Next, we screened the articles based on their title and abstract and
      only 13 articles remained. After screening based on the full text only 5 studies
      were left. Since Farsi databases did not give us the option to get all the search
      results together, we read the search results based on their titles and selected
      the relevant articles. Twenty-four studies were selected based on their title.
      After screening based on the full text, 8 studies remained. The total number of
      the studies from both English and Farsi databases that we entered in our review
      was 13. RESULT: The prevalence of physical abuse, emotional abuse and neglect in
      both genders differed from 9.7% to 67.5 %, 17.9% to 91.1% and 23.6% to 80.18%,
      respectively. The pooled estimate of the prevalence of child physical abuse in
      both genders was 43.591% (CI -216.146, 303.328%), and the pooled estimate of the
      prevalence of child emotional abuse was 64.533% (CI -195.205, 324.270). In
      regards to child neglect, the pooled estimate of the prevalence was 40.945% (CI 
      274.989, 356.879). The heterogeneity of the studies was not statically
      significant (I(2) = 0.0%). CONCLUSION: Child abuse has several negative effects
      on the health of children and adults. It seems that child abuse in Iran is in a
      critical condition, so the policy makers should act upon solving this problem and
      design special programs and develop effective policies to prevent child abuse in
      Iran.

PMID- 25561951
TI  - The translation and psychometric assessment of the persian version of the sheehan
      disability scale.
AB  - OBJECTIVE: The Sheehan Disability Scale (SDS) assesses disability in four domains
      of home management, work responsibilities, close relationships and social life.
      The main objective of this study was to develop the Persian version of the SDS.
      METHOD: Two steps of field work followed the Persian translation and cultural
      adaptation of the tool: First, the internal consistency and convergent validity
      was examined in 104 clinical cases recruited from inpatient and outpatient
      psychiatric services, using 36-item Short Form Health Survey (SF-36) and Global
      Assessment of Functioning (GAF). Then 88 individuals were randomly selected from
      the adult general population to assess internal consistency, inter-rater
      reliability and known group validity. RESULTS: In the clinical settings,
      Cronbach's alpha coefficient was 0.88 and item-total correlation ranged from 0.71
      to 0.78 in various domains. The correlation between SDS and SF-36 (P< 0.001) was
      significant in all the areas of the performance; and neither of the correlations
      was statistically significant when SDS and GAF were compared. In the general
      population study, the SDS met a good internal consistency (alpha = 0.81) and
      known group validity, and the inter-rater reliability was perfect for
      "school/work responsibility ." CONCLUSION: The Persian translation of the SDS is
      a simple and short scale, and it seems to be a valid scale for the measurement of
      disability in clinical settings and in the Iranian general population.

PMID- 25561952
TI  - Depression, anxiety and quality of life in caregiver spouses of veterans with
      chronic spinal cord injury.
AB  - OBJECTIVE: We were curious about the degree of anxiety and depression and their
      effect on the quality of life of the caregivers of veterans with spinal cord
      injury (SCI). METHODS: A convenience sample of 72 out of 120 caregiver spouses of
      veterans with spinal cord injury participated in our study. The Hospital Anxiety
      and Depression Scale (HADS) were considered as a measure of depression and
      anxiety. The World Health Organization Quality of Life BREF questionnaire (WHOQOL
      BREF) was considered to evaluate the quality of life. To compare the caregivers,
      we enrolled 74 matched caregiver spouses of patients without spinal cord injury.
      RESULTS: The average age of the spouses was 44.7+/-6.5. The average time elapsed
      from the injury was 26.4+/-3.1 years. There was a significant difference in all
      domains of quality of life and depression between the caregivers and the control
      group, but there was not a significant difference in terms of anxiety. There was
      a negative correlation between depression and age, level of education and quality
      of life. CONCLUSION: Mental care support should be implemented for veterans and
      their spouses in addition to the provided facilities.

PMID- 25561953
TI  - Borderline Personality Disorder and Religion: A perspective from a Muslim
      country.
AB  - BACKGROUND: There are still many unanswered questions about psychological and
      social factors that may affect the development and treatment of borderline
      personality disorder (BPD). Religion/spirituality (R/S) is a factor that could
      influence the lives of people with BPD. OBJECTIVE: The aim of this study was to
      evaluate the relationship between religiosity, religious attendance and
      borderline personality traits. METHOD: Four hundred twenty- nine medical students
      of Tehran University of medical sciences participated in this study, and their
      information on demographics, responses to the Duke University Religion Index
      (DUREL), and the Structured Clinical Interview for DSM-IV Axis II Disorders (the
      self-administered section on BPD) was obtained. RESULTS: The total score of SCID
      II questionnaire and the number of positive borderline personality
      characteristics on the SCID-II were inversely related with the DUREL total score
      and individual DUREL items. Those with higher levels of borderline personality
      traits had lower total DUREL score and lower DUREL subscale scores. CONCLUSION:
      Religiosity and religious attendance are negatively correlated with borderline
      personality traits, especially with anger, instability of mood, feeling of
      emptiness and self-harming behaviors. These findings are important for
      understanding the causes of BPD and in developing treatments for this disorder.

PMID- 25561954
TI  - Amantadine as Augmentation in Managing Opioid Withdrawal with Clonidine: a
      randomized controlled trial.
AB  - OBJECTIVE: Withdrawal symptoms are a main reason of continuous use of opioid.
      This study compares the efficacy of augmentation of amantadine with clonidine in
      decreasing opioid withdrawal symptoms. METHODS: This double-blind randomized
      clinical trial was carried out in the detoxification and rehabilitation inpatient
      ward at Razi Hospital, Tabriz, Iran during 2012. The patients were randomly
      assigned to receive clonidine or clonidine plus amantadine; and withdrawal
      symptoms were evaluated in the admission day and 24, 48, and 72 hours later. Data
      were analyzed using SPSS by the 2*2 repeated analyses of variances (ANOVA).
      RESULTS: From the total of 69 participants, 30 patients completed the trial in
      each group. The severity of symptoms, however, had an increasing trend in both
      groups. Analysis of variance of the symptom severity score (by The Clinical
      Opiate Withdrawal Scale) revealed a significant group-time interaction, and the
      patients who were receiving amantadine experienced milder symptoms. CONCLUSIONS:
      Treatment of opioid withdrawal symptoms with amantadine and clonidine would
      result in a better outcome compared with clonidine alone.

PMID- 25561955
TI  - The prevalence of borderline personality symptoms in adolescents.
AB  - OBJECTIVE: This study aimed to assess the prevalence of borderline personality
      symptoms in 16-18 year old adolescents. METHODS: In this cross sectional -
      descriptive study, 422 high school students (211 boys, 211 girls) aged 16-18 were
      selected by cluster random sampling and simple random sampling in 2011-2012. The
      participants were assessed using the revised diagnostic interview for borderline
      questionnaire (DIB-R) and demographic questionnaire. Data were analyzed using
      Pearson correlation coefficient and Spearman correlation coefficient. RESULTS: Of
      the participants, 0/9% (0/22 % of the 16 year olds, 0.45 % of the 17 year olds
      and 0/22% of the 18 year olds) were diagnosed with borderline personality
      symptoms. Also, the prevalence of borderline personality symptoms in boys was
      0/45 % of the total sample and it was 0/45 % of the total sample in girls. With
      respect to the relationship between demographic variables (age, sex, location,
      parents' occupation, parents' kinship, parents' education and birth order) and
      borderline personality symptoms, only parents' kinship showed a weak correlation
      with borderline personality symptoms. CONCLUSION: In the view of the prevalence
      of 0.9% of the borderline personality symptoms in adolescents, attention should
      be paid to the diagnosis and treatment of this disorder. Furthermore, works need
      to be done to improve the mental health and quality of life of adolescents.

PMID- 25561956
TI  - Cognitive functions in methamphetamine induced psychosis compared to
      schizophrenia and normal subjects.
AB  - OBJECTIVE: The purpose of this research was to study the cognitive functions in
      patients with methamphetamine-induced psychosis (MIP) in comparison with
      schizophrenia patients and normal subjects. METHOD: This was a cross-sectional
      study, 30 patients with MIP, 30 patients with schizophrenia and 30 normal
      individuals were selected via convenient sampling and were matched on age, sex
      and education. Wisconsin Cards Sorting, Stroop, Visual Search and Attention and
      Wechsler Memory Tests were used to assess the subjects. RESULTS: The study showed
      that patients with MIP and schizophrenia have more deficits in executive
      functions, selective attention, sustained attention and memory than normal
      subjects. There were no significant differences in cognitive functions between
      patients with MIP and schizophrenia except for visual search and attention that
      showed more impairment in patients with schizophrenia. CONCLUSION: Although,
      cognitive dysfunctions of patients with MIP are mostly similar to patients with
      schizophrenia, some differences seem to exist, especially in those functions that
      are not primarily dependent on frontal lobe.

PMID- 25561957
TI  - Personality Patterns in Narcotics Anonymous Members versus Individuals with
      Addiction Receiving Methadone Maintenance Therapy.
AB  - OBJECTIVE: Therapeutic interventions can be classified into two distinct
      approaches: abstinent and maintenance method. Currently, there are no clear
      criteria for referring addicted patients to one of these modalities. We aimed to
      compare the personality characteristics of individuals with addiction who
      attended narcotics anonymous sessions with those who received methadone
      maintenance therapy. METHODS: This was a cross- sectional study. The participants
      were NA members and patients who were undergoing methadone maintenance treatment
      in outpatient clinics. Using the randomized cluster sampling method, 200
      individuals with opioid dependence were selected (each group 100 persons). Data
      were collected through a demographic questionnaire and the five-factor
      personality inventory (NEO-FFI). Comparison of the mean scores of NEO-PPI in the
      two groups was performed by independent t test, and qualitative variables were
      compared using the Chi-square test. RESULTS: We found a significant difference
      between the MMT and NA groups with respect to neuroticism, extroversion, and
      agreeableness. No significant difference was found in the subscales of
      conscientious and openness. CONCLUSION: People who regularly attended the NA
      sessions had lower neuroticism and higher agreeableness than patients who were
      under the maintenance modality. Whether this is the cause or effect of attending
      NA sessions requires future large-scale cohort studies.

PMID- 25561958
TI  - To Construction and Standardization of the Waiting Anxiety Questionnaire (WAQ) in
      Iran.
AB  - OBJECTIVE: This study aimed to develop and validate a questionnaire to measure
      waiting anxiety. METHODS: This was a cross-sectional study. Extensive review of
      literature and expert opinions were used to develop and validate the waiting
      anxiety questionnaire. A sample of 321 participants was recruited through random
      cluster sampling (n= 190 Iranian men and n= 131 women). The participants filled
      out WAQ, the Speilberger's State-Trait Anxiety Inventory (STAI), Burtner Rating
      scale (BRS) and Eysenk Personality questionnaire (EPQ) for adults. RESULTS:
      Internal consistency of WAQ was revealed, meaning that all the 20 items were
      highly correlated with the total score. The Cronbach alpha equaled 0.83 for the
      Waiting Anxiety Questionnaire. The Pearson correlation coefficient of the
      questionnaire with the STAI, BRS and extraversion and neuroticism subscales of
      EPQ was 0.65, 0.78, - 0.47 and 0.43, respectively, which confirmed its convergent
      and divergent validity. Factors analysis extracting four cognitive, behavioral,
      sentimental and physiological factors could explain 67% of the total variance
      with an Eigen value of greater than 1. CONCLUSION: Our findings suggest that WAQ
      possesses appropriate validity and reliability to measure the individuals'
      anxiety during the waiting time.

PMID- 25561959
TI  - The Relationship between Perceived Sleep Quality, Polysomnographic Measures and
      Depressive Symptoms in Chemically-Injured Veterans: A Pilot Study.
AB  - OBJECTIVE: Sleep complaints are common among Iranian chemically-injured veterans.
      The growing body of research has investigated (in) equalities between such
      subjective complaints and objective sleep records. Moreover, sleep complaints are
      associated with depressive symptoms. Depressive symptoms, also, have been
      frequently reported in chemically-injured veterans. Therefore, the purpose of
      this pilot study was to investigate the relationship between perceived sleep
      quality, polysomnographic measures and depressive symptoms in Iranian veterans
      with chemical injuries. METHODS: In this pilot study, 35 Iranian veterans with
      chemical injuries complaining of a sleep problem were selected. Initially,
      participants were evaluated via all-night polysomnography, then, they completed
      the research questionnaires. Collected data were analyzed using Pearson
      correlation coefficients. RESULTS: Data analyses showed that there was no
      significant correlation between many of self-reposted variables and
      polysomnogaphic recordings, however, remarkable relationships were found between
      the Pittsburgh Sleep Quality Index and the Beck Depression Inventory scores.
      CONCLUSION: The findings indicated that sleep complaints of chemically-injured
      veterans are not equivalent to objective sleep disturbances, however, these
      complaints are largely associated with level of depression. This study emphasizes
      the important role of mood in sleep evaluation. Further, the findings suggest
      using a combination of both subjective and objective measures for accurate
      assessment of sleep quality in Iranian veterans with chemical injuries (i.e.,
      multimethod approach).

PMID- 25561960
TI  - A Multi-Center Randomized Controlled Trial of Adding Brief Skill-Based
      Psychoeducation to Primary Needle and Syringe Programs to prevent Human
      Immunodeficiency Virus: Study Protocol.
AB  - OBJECTIVES: Our objective was to design an RCT in order to assess the effects of
      adding a brief skill-based psychoeducation (PE) to routine Needle and Syringe
      Programs to reduce injection and high risk sexual behaviors associated with Human
      Immunodeficiency Virus (HIV) infection among referrals of Drop-in Centers (DICs).
      METHOD/DESIGN: This was a randomized control trial with the primary hypothesis
      that adding skill-based PE to the routine needle syringe program (NSP) provided
      in the DICs would be more effective in reducing injection and high risk sexual
      behaviors associated with HIV infection compared to the routine programs. We
      intended to randomly allocate 60 patients per group after obtaining informed
      written consent,. The intervention group receive a combination of brief
      psychoeducation consisting two individual sessions of skill-based education
      concerning blood borne viral infection, specifically HIV. The control group
      received the routine primary NSP services provided in DIC. Study assessments were
      undertaken by a psychologist at baseline, 1 and 3 months after recruitment. The
      primary outcome measure was the comparison of the trend of alterations in high
      risk sexual and injection behaviors associated with HIV infection during 3 months
      after the initiation of the intervention between the two groups. Secondary
      outcome measures included the comparison of HIV/AIDS related knowledge and client
      satisfaction in the participants. DISCUSSION: This paper presents a protocol for
      an RCT of brief skill-based PE by a trained psychologist to reduce the sexual and
      injection related high risk behaviors among drug users who received primary NSP
      services in DIC. This trial tried to investigate the efficacy of the intervention
      on increasing HIV/AIDS related knowledge and client satisfaction. The results of
      different indicators of high risk behaviors will be discussed.

PMID- 25561961
TI  - Cognitive behavioral therapy (CBT) in a Patient with Implantable Cardioverter
      Defibrillator (ICD) and Posttraumatic stress disorder(PTSD).
AB  - The implantable cardioverter defibrillator (ICD) has currently become the
      standard treatment for preventing sudden cardiac death. There are some
      psychological consequences in patients with ICD such as posttraumatic stress
      disorder (PTSD) after the shocks induced by ICD. This report aimed to present the
      case of a 54-year-old man with ICD who had developed PTSD; his PTSD was treated,
      using cognitive-behavioral psychotherapy consisting of relaxation, mindfulness
      and problem solving techniques. In patients with ICD who are experiencing PTSD
      using cognitive behavioral interventions may be helpful to reduce their
      psychological sufferings. 

PMID- 25561962
TI  - Treatment of Methamphetamine Dependence with Electroconvulsive Therapy (ECT) in
      Iran: A Critical Note.
AB  - OBJEVTIVE: This comment article reviews the literature to explore whether the use
      of ECT for the treatment of methamphetamine dependence can be justified by
      scientific rationale and/or evidence. METHOD: This article reviews the literature
      on the use of ECT in addictive disorders. It describes a patient with
      methamphetamine dependence treated with ECT. It then offers a historical review
      of the moral and ethical difficulties encountered in the treatment of addictive
      disorders. It proposes a dynamic understanding as to why clinicians might deploy
      such brutal actions in the face of hopeless and emotionally intense encounters.
      RESULTS: We found no scientific evidence or justification for ECT as a treatment
      of methamphetamine dependence or as the first line treatment for methamphetamine
      induced psychiatric comorbidities. CONCLUSION: the current available evidence
      does not support using ECT for the treatment of addictive disorders, and hence is
      unethical, unacceptable and inhumane and warrants immediate social and political
      attention.

PMID- 25561964
TI  - Ethnical variations in the incidence of congenital heart defects in gorgan,
      northern iran: a single-center study.
AB  - Background : Congenital heart disease (CHD) is the most common congenital anomaly
      in newborns. This study was performed to determine the live birth incidence of
      CHD by ethnicity and sex in Gorgan, Northern Iran. METHODS: In this longitudinal,
      hospital-based study, 18162 live births in Dezyani Hospital in Gorgan, North of
      Iran, were screened for CHD, from 2007 through 2009. Clinical examination,
      echocardiography, color Doppler, and cardio catheterization were used as
      diagnostic tools. Sex, ethnicity, and type of CHD for each case were recorded in
      a pre-designed questionnaire. Results : The incidence rates of CHD in the native
      Fars, Sistani, and Turkmen subjects were 5.73 (95%CI: 4.53-7.15), 12.27 (95%CI:
      8.74-16.73), and 15.93 (95%CI: 10.00-24.02) per 1000 live births, respectively.
      The Turkmen to native Fars and Sistani to native Fars relative risk for
      congenital CHD malformations was 2.77 (95%CI: 1.73-4.44; p value < 0.001) and
      1.29 (95%CI: 0.77-2.18; p value < 0.323), respectively. While atrial septal
      defect was the most common lesion in the native Fars subjects (2.14 per 1000
      [95%CI: 1.42-3.06]) and in the Sistani subjects (2.84 per 1000 [95%CI: 1.29
      5.36]), in the Turkmen subjects, ventricular septal defect (4.36 per 1000 [95%CI:
      1.59-9.43]), followed by atrial septal defect, was the most frequent lesion.
      Conclusion : This study showed that the incidence and pattern of CHD among live
      births in Gorgan, North of Iran, varied according to ethnicity. The risk of CHD
      was higher in the Turkmen and Sistani groups than in the Fars population.

PMID- 25561963
TI  - Cardiovascular disorders in the context of non-alcoholic Fatty liver disease: a
      literature review.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver
      disease in the United States and other industrialized countries, and the reported
      prevalence in the developing countries is also rather high. This disease is
      associated with a high rate of morbidity and mortality and damage to the other
      organs. The cardiovascular system is, perhaps, the most vulnerable organ to NAFLD
      adverse effects to the extent that most mortality associated with this disease is
      reportedly from the cardiovascular system rather than from the liver itself. In
      this article, we review the significant aspects of cardiovascular disorders
      associated with NAFLD, including the epidemiology of cardiovascular diseases in
      NAFLD patients, factors that interfere in this relationship like hypertension,
      severity of NAFLD, and age of the patients, and finally preventive strategies
      whose employment could significantly improve the outcome. 

PMID- 25561965
TI  - Discriminative Power of EuroSCORE in Predicting Morbidity and Prolonged Hospital
      Stay in an Iranian Sample Population.
AB  - BACKGROUND: The EuroSCORE is a simple and rigorous risk stratification model and
      is, thus, commonly used in predicting the early and late outcomes of cardiac
      surgery across the world. We aimed to assess the discriminative power of the
      EuroSCORE model to predict postoperative morbidity and total prolonged length of
      stay in hospital (LOS) and Intensive Care Unit (ICU) stay in an Iranian group of
      cardiac surgical population. METHODS: In a prospective study, the additive
      EuroSCORE model was applied to 570 patients undergoing isolated coronary artery
      bypass grafting (CABG) at Tehran Heart Center. The discrimination power of the
      EuroSCORE model was tested by the area under the receiver operating
      characteristic (ROC) curve and the calibration by comparing the observed and
      predicted outcomes across the risk spectrum assessed using the Hosmer-Lemeshow
      goodness-of-fit test. RESULTS: The mean age was 59.03 +/- 0.73 years and 429 out
      of the 570 (75.3%) patients were men. The overall morbidity rate was 47.5%. The
      observed morbidity in the high-risk patients (EuroSCORE > 6) was significantly
      greater than that in the low-risk patients (EuroSCORE <= 6). Furthermore, 51.2%
      of the patients had LOS beyond 14 days. Both prolonged LOS (> 14 days) and
      prolonged ICU stay (> 72 hours) were more prevalent in the high-risk group than
      in the low-risk group. The discriminative power of the EuroSCORE in predicting
      morbidity, prolonged LOS, and ICU stay was poor with an area under the ROC curve
      of 0.617, 0.598, and 0.581, respectively. However, this risk score showed good
      calibrations for morbidity (p value = 0.119), prolonged LOS (p value = 0.958),
      and prolonged ICU stay (p value = 0.620). CONCLUSION: The EuroSCORE provided
      inappropriate discrimination in predicting early morbidity and prolonged LOS and
      ICU stay in our study population. Creating a revised model may enable us to
      accurately predict outcomes in Iranian CABG patients.

PMID- 25561966
TI  - Lipid and glucose serum levels in children with congenital heart disease.
AB  - INTRODUCTION: Coronary artery disease is one of the most common causes of
      morbidity and mortality in developed countries. Atherosclerosis begins in early
      childhood and progresses through life. With advances in pediatric cardiology, the
      prevalence of congenital heart disease in adults has increased in relation to
      children. A great deal of research has been conducted on serum glucose and lipid
      concentrations in patients with congenital heart disease, but comparison has yet
      to be made between congenital patients and the general population, especially in
      pediatric groups. The aim of this study was to compare the serum concentrations
      of glucose and lipids between pediatric congenital heart disease patients and a
      healthy age and sex-matched control group. METHODS: We measured and compared the
      total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density
      lipoprotein (HDL) cholesterol, triglyceride (TG), and plasma glucose
      concentrations of 100 pediatric congenital heart disease patients (cases) and 100
      individuals matched for age and sex (controls) during a period of 7 months
      between November 2011 and June 2012. RESULTS: Total cholesterol, triglyceride,
      HDL cholesterol, and LDL cholesterol concentrations were significantly higher in
      the patients than in the control group (p value < 0.05). Blood sugar levels in
      both groups had no significant difference (p value = 0.25). In the case group,
      the cholesterol level was higher in the males than in the females (p value =
      0.30); moreover, the TG and HDL cholesterol levels were lower in the males than
      in the females and the LDL cholesterol and blood sugar levels had no
      statistically significant difference. In the control group, there was no
      difference between the males and females in terms of the cholesterol, HDL
      cholesterol, LDL cholesterol, TG, and blood sugar levels. CONCLUSION: The results
      of this study showed that our pediatric congenital heart disease patients had
      significantly higher levels of serum lipids than did their age and sex-matched
      controls. In light of these results, we recommend that the lipid profile be
      screened in children with congenital heart disease so as to reduce the risk of
      atherosclerosis.

PMID- 25561967
TI  - Association between Traditional Risk Factors and Coronary Artery Ectasia: A Study
      on 10057 Angiographic Procedures among Iranian Population.
AB  - BACKGROUND: Whether coronary artery ectasia (CAE) is a unique clinical finding or
      results from other clinical entities is still unknown. We aimed to determine the
      CAE prevalence, investigate the relationship between CAE and patients'
      demographic and clinical characteristics, and assess the prognosis at follow-up
      in a sample of Iranian population. METHODS: Totally, 10057 patients who underwent
      coronary angiography were divided into three categories: normal coronary arteries
      without co-existing coronary artery disease; CAE without co-existing coronary
      artery narrowing < 50%; and coronary artery stenosis with > 50% luminal narrowing
      (CAS). RESULTS: The prevalence of CAE was 1.5%. Compared to the normal
      individuals, the CAE patients were older, were more frequently male, and had
      higher rates of myocardial infarction (MI). The CAE patients had a lower
      frequency of diabetes and MI than the CAS group. The CAE patients were largely
      focused between 40 to 60 years of age. The right coronary and left anterior
      descending arteries were the most involved arteries, and ectasia was located more
      frequently in the proximal part of these arteries. Patients with ectasia in the
      three main vessels had higher rates of MI. After a mean follow-up of 54.23 +/-
      18.41 months, chest pain and dyspnea on exertion remained the main complaint in
      more than 97% of the patients, leading to hospital admission in more than 14%.
      CONCLUSION: There was no relationship between the presence of ectasia and
      conventional risk factors. According to our study, pure CAE may be deemed a
      benign feature of atherosclerosis; however, it can lead to frequent hospital
      admissions because of the persistence of cardiovascular symptoms.

PMID- 25561968
TI  - Effect of Enhanced External Counterpulsation (EECP) on Exercise Time Duration and
      Functional Capacity in Patients with Refractory Angina Pectoris.
AB  - BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive technique
      used for patients with refractory angina pectoris. There are controversial data
      on the effectiveness of EECP in improving patients with refractory stable angina.
      The aim of the present study was to evaluate the effectiveness and safety of EECP
      for the treatment of patients with refractory angina pectoris. METHODS: Twenty
      consecutive patients with refractory angina pectoris were treated with EECP, and
      their symptoms, echocardiographic measures, treadmill exercise test parameters,
      and Canadian Cardiovascular Society Class were evaluated before and immediately
      after EECP. The patients were followed up for 6months post treatment. RESULTS:
      There were significant differences regarding total exercise time before and after
      treatment (p value < 0.001). The patients showed a significant reduction in
      angina classes III and IV immediately after EECP (p value < 0.001); for most of
      the patients, these beneficial effects were sustained for 6 months (p value =
      0.010). There was no significant improvement in the echocardiographic parameters.
      CONCLUSION: EECP decreased symptoms and increased total exercise time in our
      study population. These beneficial effects were sustained for 6 months.

PMID- 25561970
TI  - An unusual case of mitral stenosis with coronary artery and left ventricular
      apical aneurysm.
AB  - The left ventricular aneurysm is one of the most significant complications of
      myocardial infarction and is defined as the expansion of the ventricular wall.
      The coronary artery aneurysm is characterized by an abnormal dilation of the
      localized portion of the coronary artery, and its main cause is atherosclerosis.
      We herein report an unusual case of coronary artery and left ventricular
      aneurysms in a mitral stenosis patient with normal coronary arteries and no sign
      of atherosclerosis. This patient was a known case of mitral stenosis due to
      rheumatic heart disease and was symptomatic despite optimal medical therapy.
      Laboratory tests were normal, and electrocardiography showed sinus rhythm and
      left atrium abnormality without pathologic Q wave. Angiographic view illustrated
      left circumflex artery and left ventricular apical aneurysms. Percutaneous
      transvenous mitral commissurotomy was performed successfully and the patient was
      discharged with Warfarin and a beta blocker. No symptom was observed at six
      months' follow-up. 

PMID- 25561969
TI  - Use of right ventricular support with a centrifugal pump in post-valve surgery
      right ventricular failure: a case series.
AB  - The optimal treatment method for right ventricular failure after valve surgery
      complicated by a low cardiac output has not been determined, although several
      case reports have been published on patients with ventricular failure and
      arrhythmia who were bridged to cardiac transplantation using biventricular or
      left ventricular assist devices. This case series illustrates successful
      circulatory support of 4 patients with prolonged low cardiac outputs and right
      ventricular failure and arrhythmias after valvular heart surgery with or without
      severe pulmonary hypertension. In-hospital death occurred in one patient and 3
      patients were discharged from the hospital with good general condition. At two
      years' follow-up, 2 patients were in functional class one but another patient
      underwent laparotomy for multiple splenic abscesses and died from multiple organ
      failure. 

PMID- 25561971
TI  - Percutaneous Mitral Valve Repair with the Edge-to-Edge Technique: Case Series of
      First Iranian Experience.
AB  - Mitral regurgitation (MR) is a common valvular lesion in the general population
      with considerable impact on mortality and morbidity. The MitraClip System (Abbot
      Laboratories, Abbot Park, IL, USA) is a novel percutaneous approach for treating
      MR which involves mechanical edge-to-edge coaptation of the mitral leaflets. We
      present our initial experience with the MitraClip System in 5 patients. In our
      series, the cause of MR was both degenerative and functional. Two patients
      received two MitraClips due to unsatisfactory results after the implantation of
      the first clip. Acute procedural success was seen in 4 patients. Blood
      transfusion was required for 2 patients. All the patients, except one, reported
      improvement in functional status during a 2-month follow-up period. Our initial
      experience with MitraClip implantation indicates that the technique seems
      feasible and promising with acceptable results and that it could be offered to a
      broader group of patients in the near future. 

PMID- 25561972
TI  - Intact Pleura during Left Internal Mammary Artery Harvesting in a Patient with
      kyphoscoliosis and Chronic Obstructive Pulmonary Disease.

PMID- 25561973
TI  - Fibronectin Matrix Formation is a Prerequisite for Colonization of Kidney Tumor
      Cells in Fibrin.
AB  - Fibrin plays an important role in lung metastasis. Here we show that fibrin
      promotes colony formation in primary kidney tumor cells from patients with kidney
      metastasis. In addition, we found that inhibition of fibrin formation with the
      thrombin inhibitor hirudin in nude mice in vivo significantly reduced the
      metastatic outgrowth of kidney tumor cells. Colony formation was significantly
      more efficient in tumor cells embedded in fibrin compared to matrigel and this
      effect correlates with the capacity of tumor cells to assemble a fibronectin
      matrix and generate stress fibers. Interestingly, stress fiber formation in
      fibrin was a specific function of metastatic kidney tumor cells while non
      metastatic cells remained round. Inhibition of stress fiber formation with the
      Rho kinase inhibitor Y-27632, in turn, reduced fibronectin matrix assembly and
      colony formation in fibrin suggesting that spreading is a critical mechanism for
      the outgrowth of metastatic kidney tumor cells. Overall, our results indicate
      that adhesive interactions with fibrin play an important role for the progression
      of renal cell carcinoma and that inhibiting these interactions could be a
      promising strategy for treatment and prevention of kidney cancer metastasis. 

PMID- 25561974
TI  - Colon Cancer Associated Transcript-1 (CCAT1) Expression in Adenocarcinoma of the
      Stomach.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) have been shown to have functional
      roles in cancer biology and are dys-regulated in many tumors. Colon Cancer
      Associated Transcript -1 (CCAT1) is a lncRNA, previously shown to be
      significantly up-regulated in colon cancer. The aim of this study is to determine
      expression levels of CCAT1 in gastric carcinoma (GC). METHODS: Tissue samples
      were obtained from patients undergoing resection for gastric carcinoma (n=19).
      For each patient, tumor tissue and normal appearing gastric mucosa were taken.
      Normal gastric tissues obtained from morbidly obese patients, undergoing
      laparoscopic sleeve gastrectomy served as normal controls (n=19). A human gastric
      carcinoma cell line (AGS) served as positive control. RNA was extracted from all
      tissue samples and CCAT1 expression was analyzed using quantitative real time-PCR
      (qRT-PCR). RESULTS: Low expression of CCAT1 was identified in normal gastric
      mucosa samples obtained from morbidly obese patients [mean Relative Quantity (RQ)
      = 1.95+/-0.4]. AGS human gastric carcinoma cell line showed an elevated level of
      CCAT1 expression (RQ=8.02). Expression levels of CCAT1 were approximately 10.8
      fold higher in GC samples than in samples taken from the negative control group
      (RQ=21.1+/-5 vs. RQ=1.95+/-0.4, respectively, p<0.001). Interestingly, CCAT1
      expression was significantly overexpressed in adjacent normal tissues when
      compared to the negative control group (RQ = 15.25+/-2 vs. RQ=1.95+/-0.4,
      respectively, p<0.001). Tissues obtained from recurrent GC cases showed the
      highest expression levels (RQ = 88.8+/-31; p<0.001). Expression levels increased
      with tumor stage (T4- 36.4+/-15, T3- 16.1+/-6, T2- 4.7+/-1), however this did not
      reach statistical significance (p=0.2). There was no difference in CCAT1
      expression between intestinal and diffuse type GC (RQ=22.4+/-7 vs. 22.4+/-16,
      respectively, p=0.9). Within the normal gastric tissue samples, no significant
      difference in CCAT1 expression was observed in helicobacter pylori negative and
      positive patients (RQ= 2.4+/-0.9 vs. 0.93+/-0.2, respectively, p=0.13).
      CONCLUSION: CCAT1 is up-regulated in gastric cancer, and may serve as a potential
      bio-marker for early detection and surveillance.

PMID- 25561975
TI  - Identification of Stably Expressed lncRNAs as Valid Endogenous Controls for
      Profiling of Human Glioma.
AB  - BACKGROUND: Recent research indicates that long non-coding RNAs (lncRNA)
      represent a new family of RNAs that is of fundamental importance for controlling
      transcription and translation. Thereby, there is increasing evidence that lncRNAs
      are also important in tumourigenesis. Thereby valid expression profiling using
      quantitative PCR requires suitable, stably expressed normalisers to achieve
      reliable and reproducible data. However, no systematic analysis of suitable
      references in lncRNA studies in human glioma has been performed yet. METHODS: In
      this study, we investigated 90 lncRNAs in 30 tissue specimen for the expression
      stability in human diffuse astrocytoma (WHO-Grade II), anaplastic astrocytoma
      (WHO-Grade III) and glioblastoma (WHO-Grade IV) both alone as well as in
      comparison with normal white matter. Our identification procedure included a
      rigorous bioinformatical selection process that resulted in the inclusion of only
      highly abundant, equally expressed lncRNAs for further analysis. Additionally,
      lncRNAs were classified according to their stability value using the NormFinder
      algorithm. RESULTS: We identified 24 appropriate normalisers suitable for studies
      in diffuse astrocytoma, 22 for studies in anaplastic astrocytoma and 12 for
      studies in glioblastoma. Comparing all three glioma entities 7 lncRNAs showed
      stable expression levels. Addition of normal brain tissue resulted in only 4
      suitable lncRNAs. CONCLUSIONS: Our findings indicate that 4 lncRNAs (HOXA6as, H19
      upstream conserved 1 and 2, Zfhx2as and BC200) are suitable as normalisers in
      glioma and normal brain. These lncRNAs may thus be regarded as universal
      references being applicable for the accurate normalisation of lncRNA expression
      profiling in various glioma (WHO-Grades II-IV) alone and in combination with
      brain tissue. This enables to perform valid longitudinal studies, e.g. of glioma
      before and after malignisation to identify changes of lncRNA expressions probably
      driving malignant transformation.

PMID- 25561976
TI  - Three-step hand-assisted laparoscopic d2 radical gastrectomy for chinese obese
      patients: a highly efficient and feasible surgical approach.
AB  - Three-step hand-assisted laparoscopic D2 radical gastrectomy (HALG) is a modified
      surgical procedure that has achieved satisfactory results for obese patients in
      our surgical center. To fully elucidate the advantages of this procedure, in this
      study, comprehensive and in-depth comparative analyses were performed to assess
      clinical data from obese gastric cancer patients who underwent HALG, laparoscopic
      assisted D2 radical gastrectomy (LAG), and open D2 radical gastrectomy (OG) in
      our surgical center during a specific time period. For the 3 groups, incision
      length was 1.25 cm longer for the HALG group than for the LAG group but was
      significantly shorter for the HALG group than for the OG group (P =0.00). The
      rate of conversion to laparotomy , the pneumoperitoneum time and the number of
      recovered lymph nodes were significantly better for the HALG group than for the
      LAG group (P <0.05). The pain score at day 2 after surgery, intestinal function
      recovery time, and duration of postoperative hospital stay were not significantly
      different for the HALG and LAG groups ( P >0.05) but were significantly better
      for the HALG group than for the OG group (P <0.05). There were significantly
      fewer postoperative complications for the HALG group than for the LAG and OG
      groups (P =0.049). According to the results, the "three-step HALG method"
      incorporates both the thoroughness of the radical OG approach and the minimal
      invasiveness of the LAG approach for obese patients. Thus, the HALG approach is a
      relatively safe and extremely feasible surgical procedure for the treatment of
      these patients. 

PMID- 25561977
TI  - The quantum of initial transformed cells potentially modulates the type of local
      inflammation mechanism elicited by surrounding normal epithelial tissues and
      systemic immune pattern for tumor arrest or progression.
AB  - The immune/ inflammation system potentially serves to arrest, eliminate or
      promote tumor development. Nonetheless, factors that dictate the choice are not
      comprehensively known yet. Using a B16/F1 syngeneic wild type model, we evaluated
      the essentiality of initial transformed cells' density for overt tumor
      development, the molecular trends of inflammatory mediators in the normal tumor
      adjacent epithelial tissues (NTAT), and how such local events may reflect
      systematically in the host. Overt tumors developed, within an observatory period
      of at least 45 days and 90 days at most, only in mice inoculated with cancer
      cells above a limiting threshold of 1* 10(3) cells. Immunoblots showed early,
      intense and transient presence of IL-1beta, IFN-gamma, and both the all-thiol and
      disulfide forms of HMGB1 in the NTAT of non-tumor bearing mice. However, all
      thiol form of HMGB1 and delayed but aberrant IL-6 expression characterized
      chronic inflammation in tumor bearing hosts. These local epithelial tissue events
      uniquely reflected in host's systemic cytokines dynamics where stable Th1/Th2
      signature (IFN-gamma/ IL-4) coupled with early Th1 cells polarization (IL-12/ IL
      4) evidenced in non-tumor hosts but highly fluctuating Th1/ Th2 profile in tumor
      hosts, even before tumors became overt. This hypothesizes that the physical
      quantum of transformed cells that may either spontaneously arise or accrue at a
      locus may be crucial in orchestrating the mechanism for the type of local
      epithelial tissue and systemic immune/ inflammatory responses essential for tumor
      progression or arrest. 

PMID- 25561978
TI  - Could GLUT12 be a Potential Therapeutic Target in Cancer Treatment? A Preliminary
      Report.
AB  - BACKGROUND: Recent studies proposed GLUT12 to be a major glucose transporter
      involved in the glycolytic metabolism of cancer cells. METHODS: GLUT12 expression
      was determined by immunohistochemistry in a selection of cancer cell lines and a
      tumour spheroid model. RESULTS: GLUT12 expression was high in A549 and RH-36; low
      in HT29; and absent in NB-EB cancer cell lines. GLUT12 expression was located in
      the necrotic centre of HT29 spheroids, which is characterised by anaerobic
      metabolism. CONCLUSION: The data supports the involvement of GLUT12 in the
      glycolytic metabolism of cancer cells and therefore, its potential as a novel
      therapeutic target for cancer treatment.

PMID- 25561979
TI  - The quality of tumor size assessment by contrast-enhanced spectral mammography
      and the benefit of additional breast MRI.
AB  - Background - Contrast-enhanced spectral mammography (CESM) is a promising new
      breast imaging modality that is superior to conventional mammography for breast
      cancer detection. We aimed to evaluate correlation and agreement of tumor size
      measurements using CESM. As additional analysis, we evaluated whether
      measurements using an additional breast MRI exam would yield more accurate
      results. Methods - Between January 1(st) 2013 and April 1(st) 2014, 87
      consecutive breast cancer cases that underwent CESM were collected and data on
      maximum tumor size measurements were gathered. In 57 cases, tumor size
      measurements were also available for breast MRI. Histopathological results of the
      surgical specimen served as gold standard in all cases. Results - The Pearson's
      correlation coefficients (PCC) of CESM versus histopathology and breast MRI
      versus histopathology were all >0.9, p<0.0001. For the agreement between
      measurements, the mean difference between CESM and histopathology was 0.03 mm.
      The mean difference between breast MRI and histopathology was 2.12 mm. Using a
      2x2 contingency table to assess the frequency distribution of a relevant size
      discrepancy of >1 cm between the two imaging modalities and histopathological
      results, we did not observe any advantage of performing an additional breast MRI
      after CESM in any of the cases. Conclusion - Quality of tumor size measurement
      using CESM is good and matches the quality of these measurement assessed by
      breast MRI. Additional measurements using breast MRI did not improve the quality
      of tumor size measurements. 

PMID- 25561980
TI  - Effects of mitochondrial translocation of telomerase on drug resistance in
      hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) cells exhibit multidrug resistance (MDR), but the
      underlying mechanisms remain unclear. Cancer cells that overexpress telomerase
      are resistant to chemotherapeutic drugs. This study aimed to determine the
      effects of mitochondrial translocation of telomerase on MDR in HCC cells. HepG2
      cells were transfected with negative plasmid and PTPN11 (Shp-2) short hairpin RNA
      (ShRNA) plasmid to establish HepG2-negative (HepG2 transfected with negative
      plasmid) and HepG2-ShShp-2 (HepG2 transfected with Shp-2 ShRNA plasmid) cells.
      Sensitivity to chemotherapeutic drugs was assessed by Cell Counting Kit-8 (CCK-8)
      assays. Distribution of human telomerase reverse transcriptase (hTERT) within
      mitochondria was detected by western blotting and immunofluorescence combined
      with laser scanning confocal microscopy. Mitochondrial reactive oxygen species
      (ROS) generation was demonstrated by flow cytometry with the mitochondrial
      superoxide (Mito-Sox) indicator. The frequency of damaged mitochondrial DNA
      (mtDNA) was illustrated by quantitative real-time polymerase chain reaction (Q
      PCR). Expression of mitochondrial respiratory chain complex subunits ND1 and
      COXII were also demonstrated by western blotting. Knockdown of Shp-2 in HepG2
      cells resulted in upregulation of mitochondrial TERT expression and increased
      resistance to cisplatin (CDDP) and 5-fluorouracil (5-FU) (resistance indices,
      2.094 and 1.863, respectively). In addition, both the mitochondrial ROS and the
      frequency of mtDNA damage were decreased, and COXII expression was upregulated.
      Our results suggest that Mitochondrial translocation of hTERT may lead to
      chemotherapeutic resistance in HCC cells. Mitochondrial hTERT contributes to the
      drug resistance of tumor cells by reducing ROS production and mtDNA damage, and
      exerting a protective effect on the mitochondrial respiratory chain. 

PMID- 25561981
TI  - The Analysis of the Relationship between Multiple Myeloma Cells and Their
      Microenvironment.
AB  - The bone marrow microenvironment plays a key role in the stimulation of growth
      and survival of multiple myeloma (MM) cells. We investigated whether membrane
      microfragments (MFBs) exert a stimulatory effect on mesenchymal stem cell (MSC)
      gene expression or differentiation. MSCs from patients with multiple myeloma
      (MMBM-MSCs) proliferated at a slower rate than MSCs from healthy volunteers (BM
      MSCs), and fewer MMBM-MSCs adhered to the substrate as compared to BM-MSCs.
      Phenotypic analysis revealed that MMBM-MSCs and BM-MSCs differed significantly in
      terms of their CD166 and CXCR4 expressions. In conclusion, our comparative
      analysis of mesenchymal cells from MM patients and healthy volunteers revealed
      differences in the genetic and phenotypic profiles of these two populations,
      their potential for osteodifferentiation, and expression of surface antigens.
      Moreover, we showed that membrane MFBs may alter the genetic profile of MSCs,
      leading to disorders of their osteodifferentiation, and interact with the WNT
      pathway via presentation of the DKK-1 protein. 

PMID- 25561983
TI  - Brain and central nervous system cancer incidence in navarre (Spain), 1973-2008
      and projections for 2014.
AB  - Different studies have pointed out Navarre as one of the regions of Spain with
      the highest incidence rates of brain and other central nervous system (CNS)
      cancer. Trend analysis for cancer incidence rates for long periods of time, might
      help determining risk factors as well as, assessing prevention actions involved
      in this disease. The objective of this study was to describe the incidence of
      brain and CNS cancer using data from the population-based cancer registry of
      Navarre, (Spain) during the period 1973-2008 and provide forecast figures up to
      2014. Crude and age-standardized (world population) incidence rates of brain
      cancer per 100,000 person-years were calculated by the direct method separately
      by gender, area (Pamplona and others), and age-groups. Penalized splines for
      smoothing rates in the temporal dimensions were applied in order to estimate and
      forecast cancer incidence rates. Age-adjusted incidence rates showed an increase
      over the study and forecast periods in both sexes more marked in women than in
      men. Higher incidence rates were observed in men compared with women but the
      differences became smaller with time. The increase was due to the rise of rates
      in the oldest age groups since the rates for younger age groups remained stable
      or decreased over time. As the entire aetiology of brain and other CNS cancer is
      not still clear, keep promoting healthful lifestyles for cancer primary
      prevention among the whole population is necessary. 

PMID- 25561982
TI  - The assessment of tumor response by measuring the single largest lesion per organ
      in metastatic tumors: a pooled analysis of previously reported data.
AB  - BACKGROUND: The RECIST 1.1 adopted a total of five target lesions to be measured,
      with a maximum of two lesions per organ. To the best of our knowledge, the
      criterion of two target lesions per organ in the RECIST 1.1 is arbitrary and has
      not been supported by any objective evidence. Recently, we reported that the
      modified RECIST 1.1 (measuring the single largest lesion in each organ) showed a
      high level of concordance with the original RECIST 1.1 in patients with advanced
      or metastatic non-small cell lung cancer (NSCLC), gastric cancer (GC), and
      colorectal cancer (CRC). However, each study had a major limitation of a small
      number of patients. METHODS: We conducted a pooled analysis using the data from
      the three individual studies to improve statistical power. Tumor responses were
      compared according to the RECIST 1.1 and modified RECIST 1.1 (mRECIST 1.1).
      RESULTS: A total of 153 patients who had at least two target lesions in any organ
      according to the RECIST 1.1 were included in this pooled study: 64 with NSCLC, 51
      with GC, and 38 with CRC. Regardless of primary sites, the number of target
      lesions according to the mRECIST 1.1 was significantly lower than that according
      to the RECIST 1.1 (P<0.001). The assessment of tumor responses showed a high
      concordance between the two criteria (k = 0.908). Only eight patients (5.2%)
      showed disagreement in the tumor response assessment between the two criteria.
      The overall response rates of chemotherapy were not significantly different
      between the two criteria (33.3% versus 33.3%, P=1.0). CONCLUSIONS: The modified
      RECIST 1.1 was comparable to the original RECIST 1.1 in the tumor response
      assessment of patients with advanced or metastatic NSCLC, GC, and CRC. Our
      results suggest that it may be possible to measure the single largest lesion per
      organ for assessing tumor response in clinical practice.

PMID- 25561984
TI  - Video-assisted thoracic surgery complications.
AB  - Video-assisted thoracic surgery (VATS) is a miniinvasive technique commonly
      applied worldwide. Indications for VATS are very broad and include the diagnosis
      of mediastinal, lung and pleural diseases, as well as large resection procedures
      such as pneumonectomy. The most frequent complication is prolonged postoperative
      air leak. The other significant complications are bleeding, infections,
      postoperative pain and recurrence at the port site. Different complications of
      VATS procedures can occur with variable frequency in various diseases. Despite
      the large number of their types, such complications are rare and can be avoided
      through the proper selection of patients and an appropriate surgical technique. 

PMID- 25561985
TI  - Percutaneous nephrostomy for symptomatic hypermobile kidney: a single centre
      experience.
AB  - INTRODUCTION: Symptomatic hypermobile kidney is treated with nephropexy, a
      surgical procedure through which the floating kidney is fixed to the
      retroperitoneum. Although both open and endoscopic procedures have a high success
      rate, they can be associated with risk of complications, relatively long hospital
      stay and high cost. AIM: We describe our percutaneous technique for fixing a
      hypermobile kidney and evaluate the efficacy of the percutaneous nephrostomy
      insertion in management of symptomatic nephroptosis. MATERIAL AND METHODS:
      Between January 2005 and December 2011, 11 patients diagnosed with a symptomatic
      right nephroptosis of at least 1 year duration were treated with a single point
      percutaneous nephrostomy technique. All data were retrieved from patients'
      medical records and then retrospectively analysed. RESULTS: Nephropexy through a
      single point percutaneous nephrostomy technique was successfully accomplished in
      11 women. The mean operative time was 20 min. The intraoperative estimated blood
      loss was minimal in all cases. No major or minor intraoperative complications
      were noted. The average postoperative hospital stay was 2 days. Women returned to
      their usual activities 14 days following the surgery. Nine women had complete
      resolution of their pain, and 2 patients continued to complain of discomfort in
      their lumbar area. One patient was re-operated upon with satisfactory subjective
      and objective outcomes achieved. One patient refused re-operation. CONCLUSIONS:
      Percutaneous nephropexy is simple, inexpensive and effective for treatment of
      symptomatic hypermobile kidney. It remains a valuable alternative to open,
      laparoscopic, and robotic methods for fixing a floating kidney.

PMID- 25561986
TI  - Sialendoscopy - a diagnostic and therapeutic approach subjectively rated by
      patients.
AB  - INTRODUCTION: Sialendoscopy is a miniinvasive procedure which shows the excretory
      ducts of the salivary glands. AIM: To evaluate patient satisfaction with
      sialendoscopy in submandibular and parotid gland sialolithiasis. MATERIAL AND
      METHODS: The study group included 100 consecutive patients with sialolithiasis,
      treated by means of sialendoscopy. The analysis was designed prospectively. The
      patients answered closed questions of our own, in-house made questionnaire.
      RESULTS: The number of sialendoscopic procedures necessary for symptom resolution
      ranged from 1 to 3. The mean value was 1.2 and the median was 1. In 64 patients
      (64%) one procedure was sufficient for symptom resolution, while 10 (10%) and 8
      (8%) patients required 2 and even 3 procedures, respectively. Sixty-three
      patients (63%) did not report any postoperative complications; 33 patients (33%)
      reported transient swelling of the submandibular region and 4 patients (4%)
      reported inflammation of the salivary gland. The level of treatment efficacy was
      82%. Among 53 patients treated using sialendoscopy for the first time 92.3% rated
      this approach subjectively as a very good or good technique, whereas among 47
      patients who had previously undergone non-endoscopic treatment, this percentage
      increased to 96.4%. The general level of satisfaction with the applied method did
      not depend on the age, gender, duration of ailments, the number of previously
      performed procedures or the number of sialendoscopic procedures necessary to
      obtain improvement and postoperative complications. CONCLUSIONS: Sialendoscopy
      may be performed practically in any case without risking the patient's discomfort
      or unpleasant experience. Assessment of sialendoscopy by the patients confirmed
      the minimally invasive character of this technique.

PMID- 25561987
TI  - Robotic stereotactic body radiation therapy for liver-limited malignant tumors.
AB  - INTRODUCTION: Stereotactic body radiotherapy (SBRT) is rapidly gaining favor as a
      new treatment modality for malignant liver tumors. Most of the studies have
      recruited patients with disseminated disease originating from the liver. This
      study focuses on disease limited to the liver. AIM: To perform a retrospective
      analysis of all patients with liver tumors treated by robotic stereotactic body
      radiation therapy in a single center. MATERIAL AND METHODS: The study included 13
      patients with 22 lesions. The inclusion criteria were: patients with 1-4
      inoperable liver lesions and absence of any extrahepatic disease. All but 3
      patients received 3 fractions delivered by the Cyberknife system of a total of 45
      grey (Gy). The other 3 patients received 30 Gy. RESULTS: The median follow-up
      time was 10.8 months (range: 7-16). The median dose was 41.5 Gy (range: 30-45).
      One lesion regressed (8%). In 5 patients, the disease was locally stabilized
      (38%), and in 7 other patients progression occurred (54%). Twelve patients (92%)
      are still alive, and 1 patient (8%) died. In 1 patient a new cancer (leukemia)
      was diagnosed. CONCLUSIONS: The SBRT is well tolerated and effective for local
      control of most liver malignant tumors. It appears that SBRT is best suited for
      those patients in whom systemic recurrence can be controlled by chemotherapy.
      Further studies are mandatory to elucidate these effects on tumors of varying
      histology and to elaborate upon criteria used to select patients who can benefit
      most from this treatment.

PMID- 25561988
TI  - A non-invasive screening technique for type 1 autoimmune pancreatitis.
AB  - INTRODUCTION: Type 1 autoimmune pancreatitis (AIP) is the pancreatic
      manifestation of a systemic fibroinflammatory IgG4-related disease. Accurate
      diagnosis of AIP can avoid major hepatobiliary and pancreatic surgery as it
      respond dramatically to corticosteroid therapy. AIM: This research investigated
      the feasibility of using peripheral blood cell immunohistochemistry, serum IgG4,
      T-cell receptor (TCR) and serum isoelectric focusing electrophoresis in the
      screening of type 1 autoimmune pancreatitis (AIP). MATERIAL AND METHODS: The
      peripheral blood from 3 type 1 AIP patients, 10 pancreatic cancer patients and 40
      normal controls was collected. Sediment smears were jointly incubated with anti
      IgG4 and anti-IgG. The percentage of IgG4/IgG positive cells was counted and
      serum TCR and IgG4 were detected through the whole process. After serum
      isoelectric focusing electrophoresis, anti-IgG4 and anti-IgG were used to confirm
      the components of serum. RESULTS: In the serum isoelectric focusing
      electrophoresis, IgG4 and IgG strips showed mirrored distribution in type 1 AIP
      patients, while there were no strips in the normal controls and pancreatic
      cancer. Compared with pancreatic tumor patients and healthy controls, serum TCR
      was significant increased in AIP. The percentage of IgG4/IgG positive cells of
      peripheral blood cell immunohistochemistry was related to serum IgG4 and hormone
      therapy reactions. CONCLUSIONS: Peripheral blood cell immunohistochemistry, serum
      IgG4, TCR and serum isoelectric focusing electrophoresis is suitable for the
      screening of type 1 AIP and monitoring its response assessment.

PMID- 25561989
TI  - Dynamics of type 2 diabetes mellitus laboratory remission after Roux-en-Y gastric
      bypass in patients with body mass index lower than 35 kg/m(2) and higher than 35
      kg/m(2) in a 3-year observation period.
AB  - INTRODUCTION: Bariatric surgery as treatment of type 2 diabetes mellitus (T2DM)
      in morbidly obese patients is becoming common. Although a large number of studies
      demonstrating high efficacy of bariatric methods in diabetics with body mass
      index (BMI) < 35 kg/m(2) have been published, this promising solution is still
      not accepted enough even in the era of a diabetes offensive. AIM: To analyze the
      dynamics of T2DM remission in patients with BMI < 35 kg/m(2) and > 35 kg/m(2)
      after Roux-en-Y gastric bypass (RYGB). MATERIAL AND METHODS: Data of 30 patients
      with BMI < 35 kg/m(2) and 82 with BMI > 35 kg/m(2) who underwent RYGB between
      2007 and 2010 were collected from a prospectively designed database. The
      laboratory resolution of T2DM was determined by fasting plasma glucose (FPG <=
      100 mg/dl) and glycosylated hemoglobin (HbA1c <= 6%). RESULTS: The T2DM
      regression was observed in 80% of the patients with BMI < 35 kg/m(2) and 83% in a
      group with BMI > 35 kg/m(2) 1 year after RYGB and about 80% 2 and 3 years after
      the operation in both groups. Normalization of average HbA1c and FPG was observed
      in the BMI > 35 kg/m(2) group after 3 months, while in the BMI < 35 kg/m(2) group
      it was reached 6 months postoperatively. Changes in main markers of T2DM were
      parallel with the BMI decrease 3-12 months after RYGB, but early resolution in
      some patients was observed independently of weight loss. CONCLUSIONS: The mid
      term observation of patients after RYGB revealed the laboratory remission of
      T2DM. Ultimate evaluation of T2DM markers 3 years after surgery demonstrates high
      effectiveness of RYGB in managing T2DM in both groups.

PMID- 25561990
TI  - Image-based guidance of percutaneous abdomen intervention based on markers for
      semi-automatic rigid registration.
AB  - INTRODUCTION: For percutaneous abdomen intervention (e.g. liver radiofrequency
      (RF) tumor ablation, liver biopsy), surgeons lack real-time visual feedback about
      the location of the needle on planning images, typically computed tomography
      (CT). One difficulty lies in tracking and synchronizing both the tool movement
      and the patient breathing motion. AIM: To verify the correspondence between rigid
      registration fiducial registration error signal and breathing phase. MATERIAL AND
      METHODS: Designed markers that are clearly visible both in planning CT and on the
      patient during the intervention are proposed. Registration and breathing
      synchronization is then performed by a point-based approach. The method was
      tested in a clinical environment on 10 patients with liver cancer using 3D
      abdominal CT in the exhale position. Median rigid fiducial registration error
      (FRE) in the breathing cycle was used as a criterion to distinguish the inhale
      and exhale phase. RESULTS: The correlation between breathing phase and FRE value
      can be observed for every patient. We obtained mean median FRE equal to 9.37 mm
      in exhale positions and 15.56 mm in the whole breathing cycle. CONCLUSIONS: The
      presented real time approach, based on FRE calculation, was integrated in the
      clinical pipeline, and can help to select the best respiratory phase for needle
      insertion for percutaneous abdomen intervention, in cases where only 3D CT is
      performed. Moreover, this method allows semi-automated rigid registration to
      establish the correspondence between preoperative patient anatomical model and
      patient position.

PMID- 25561991
TI  - A retrospective case-controlled study of video-assisted versus open minimally
      invasive parathyroidectomy.
AB  - INTRODUCTION: Minimally invasive parathyroidectomy (MIP) with intraoperative
      parathyroid hormone assay (IOPTH) has successfully replaced conventional neck
      exploration in most patients with primary hyperparathyroidism (pHPT) and
      preoperatively localized parathyroid adenoma. AIM: To compare outcomes of video
      assisted MIP (MIVAP) to open MIP (OMIP). MATERIAL AND METHODS: A retrospective
      case-controlled study of 455 patients with sporadic pHPT undergoing MIP with
      IOPTH at our institution in 2003-2012 was undertaken. The primary outcome measure
      was postoperative pain. Secondary outcome measures were: duration of surgery,
      recurrent laryngeal nerve (RLN) identification rate, conversion rate, length of
      hospital stay, cure rate, patients' satisfaction with cosmetic outcome,
      morbidity, costs, and diagnostic accuracy of IOPTH. RESULTS: Of 455 patients with
      pHPT and a solitary parathyroid adenoma on preoperative imaging, 151 underwent
      MIVAP and 304 had OMIP. The following outcomes were favourable for MIVAP vs.
      OMIP: lower pain intensity during 24 h postoperatively (p < 0.001), lower
      analgesia request rate (p < 0.001), lower analgesics consumption (p < 0.001),
      higher recurrent laryngeal nerve identification rate (p < 0.001), shorter scar
      length (p < 0.001), and better cosmetic satisfaction at 1 month (p = 0.013) and
      at 6 months (p = 0.024) after surgery. However, MIVAP vs. OMIP had longer
      duration of surgery (p < 0.001), and was more expensive (p < 0.001). No
      differences were noted in the conversion rate, length of hospital stay, and
      morbidity. CONCLUSIONS: Both MIVAP and OMIP approaches were equally safe and
      effective. However, the outcomes of MIVAP operations were superior to OMIP in
      terms of lesser postoperative pain, lower analgesics consumption, and better
      cosmetic satisfaction resulting from a smaller scar.

PMID- 25561992
TI  - The treatment of chronic pleural empyema with laparoscopic omentoplasty. Initial
      report.
AB  - INTRODUCTION: Pleural empyema is the most serious, life-threatening postoperative
      complication of pneumonectomy, observed after 1-12% of all pneumonectomies, with
      bronchopleural fistula being its main cause. AIM: The aim of this publication is
      to present early outcomes of minimally invasive surgical management of pleural
      empyema. Patients were subjected to a single, complex procedure, consisting of
      the laparoscopic mobilization of the greater omentum and its transposition via
      the diaphragm into the pleural cavity to fill in the empyema cavity with the
      consecutive pleuro-cutaneous fistuloplasty (thoracoplasty). MATERIAL AND METHODS:
      Between May 2011 and April 2013, 8 patients were qualified to undergo the
      procedure. The mean age was 61 years (range: 46-77 years). Presence of
      bronchopleural fistula was confirmed in 3 cases. The median time of treatment
      with thoracostomy was 14.5 months. RESULTS: The mean operative time was 125 min.
      The mean duration of post-operative hospital stay was 13.5 days (range: 7-31
      days). In 6 patients (75%) the objective of permanent resolution of pleural
      empyema was achieved. In total, 4 patients had complications: pleural empyema
      recurrence (2 patients), splenic injury, hiatal hernia, gastrointestinal bleed.
      Two patients with empyema recurrence had Staphylococcus aureus infections prior
      to surgery. They were successfully managed both with prolonged thoracic drainage
      and antibiotics. CONCLUSIONS: Use of the greater omentum that was
      laparoscopically mobilized and transpositioned into the pleural cavity allows
      simultaneous management of the pleural empyema cavity and thoracostomy. The
      procedure is safe, with few direct complications. It is well tolerated and has at
      least a satisfactory cosmetic effect. The minimally invasive approach allows
      faster recovery and return to daily activities in comparison to the fully open
      technique.

PMID- 25561993
TI  - Dietary intake and ghrelin and leptin changes after sleeve gastrectomy.
AB  - INTRODUCTION: Surgical intervention in obesity is today the most effective
      treatment method in high level obesity management. Bariatric interventions not
      only ensure body weight reduction, but may influence dietary habits. AIM: To
      assess changes in adipose hormones and dietary habits in obese patients after
      sleeve gastrectomy. MATERIAL AND METHODS: The study set comprised 37 subjects (29
      females and 8 males) 24 to 68 years old with body mass index 43.0 +/-4.9 kg/m(2).
      Pre-operative examination included baseline measurements of body composition.
      Dietary habits and intake frequency were monitored by a questionnaire method.
      Follow-up examinations were carried out in a scope identical to the pre-operative
      examination, 6 and 12 months after surgery, respectively. RESULTS: The average
      patient weight loss 12 months after surgery was 31.7 kg. Excess weight loss was
      55.2 +/-20.6%. Patients reported reduced appetite (p < 0.001), increasingly
      regular food intake (p < 0.001), intake of more meal portions per day (p = 0.003)
      and a decrease in consuming the largest portions during the afternoon and evening
      (p = 0.030). Plasma levels of fasting glucose, leptin and ghrelin significantly
      decreased (p = 0.006; p = 0.0.043); in contrast, the level of adiponectin
      significantly increased (p < 0.001). CONCLUSIONS: Sleeve gastrectomy and follow
      up nutritional therapy resulted in a significant body weight reduction within 1
      year after surgery. An improvement of certain dietary habits in patients was
      registered. At 12 months after surgery, there were no statistically significant
      differences in decreases in ghrelin and leptin concentrations between patients
      without changed appetite and those reporting decreased appetite.

PMID- 25561994
TI  - Beginning robotic assisted colorectal surgery - it's harder than it looks!
AB  - INTRODUCTION: Laparoscopy has been introduced into the field of colorectal
      surgery with the aim of reducing morbidity. One of the major barriers to overcome
      is the steep learning curve. Robotic surgery offers substantial advantages over
      traditional laparoscopy, which make the whole procedure more user friendly. AIM:
      To present our initial experiences with robotic assisted colorectal surgery.
      MATERIAL AND METHODS: Thirty-five patients with colorectal cancer underwent
      robotic assisted procedures between 2011 and 2013. RESULTS: In total we performed
      16 low anterior resections, 14 right colectomies, 3 abdominosacral resections and
      2 left colectomies. There were 22 males and 13 females. The mean operative time
      was 315 +/-65 min for a low anterior resection. The mean length of hospital stay
      was 6.4 +/-1 days. There were 4 conversions to open procedures, 2 anastomotic
      leaks, and 1 colovaginal fistula. The mean lymph node yield was 12.7 +/-4.3. The
      resection margin was negative in all but 1 patient. CONCLUSIONS: We agree with
      the opinion that robotic surgery brings many advantages in pelvic dissections. In
      order to facilitate safe acquisition of robotic total mesorectal excision skills,
      surgeons should begin with female patients, and less advanced rectal cancer. In
      some instances robotic assistance can be helpful in right colectomies.

PMID- 25561995
TI  - Higher risk of incomplete mesorectal excision and positive circumferential margin
      in low rectal cancer regardless of surgical technique.
AB  - INTRODUCTION: Currently, the predominant question is whether a laparoscopic
      approach is comparatively radical in comparison with an open access approach,
      especially in the circumferential resection margin and quality of the
      completeness of total mesorectal excision. These factors are important in
      determining the quality of surgical care as well as long-term results of the
      treatment. AIM: This article focuses on the evaluation of circumferential
      resection margins and on the quality of mesorectal excision of middle and lower
      rectum tumors. In addition, laparoscopic and open techniques are compared.
      MATERIAL AND METHODS: Data were collected prospectively and stored in a rectal
      cancer registry over a 3-year period. The parameters studied were age, sex, body
      mass index, localization and topography of the tumor, clinical stage, neoadjuvant
      chemotherapy and its response, the type of surgery, character of the
      circumferential and distal margins, quality of the mesorectal excision, pT and
      pN. RESULTS: One hundred and twenty-five patients were chosen for our study.
      Laparoscopy was performed in 53 operations and a conventional approach was
      performed in 72 operations. Complete mesorectal excision was achieved in 54.7% of
      laparoscopic operations versus 44.4% in the conventional technique; partially
      complete excision was performed in 20.8 and 12.5%, respectively. Incomplete
      excisions were described in 24.5 and 43.1% (p = 0.085). Positive circumferential
      margin occurred during laparoscopic surgery in 11 (20.8%) patients, and in the
      case of conventional resection in 27 (37.5%) patients (p = 0.044). CONCLUSIONS:
      Our study showed comparable results between laparoscopic and open access
      procedures during rectal resection. The results achieved, in particular in the
      quality of the mesorectal excision and negative circumferential resection margin,
      show that the laparoscopic approach is comparable to conventional surgical
      techniques, with an adequate surgical outcome, in the treatment of rectal cancer.

PMID- 25561996
TI  - Laparoscopic closure of perforated gastro-duodenal ulcer: 15 years' experience in
      our centre.
AB  - INTRODUCTION: The objective of the study is to share the results and development
      findings on the laparoscopic closure technique applied in our centre during a 15
      year period (1998-2012). AIM: To compare statistically the standard parameters
      (hospitalization, duration of operation) versus conventional surgery, and at the
      same time we compared mainly morbidity and mortality. MATERIAL AND METHODS:
      During the period under review we operated on a total of 259 patients, 115
      (44.4%) of them laparoscopically, and 144 (55.6%) of them conventionally. The
      sample was divided into two groups: patients with ASA physical status
      classification system 1-3, and patients with ASA 4-5. RESULTS: The results favour
      laparoscopy within the group with ASA 1-3 in terms of several parameters, namely:
      duration of hospitalization - 7.7 days in the case of laparoscopic intervention,
      vs. 10.6 days for conventional surgery (p < 0.05); and duration of operation - 61
      min vs. 85.1 min respectively (p < 0.05). Total morbidity was 27.5% in the case
      of patients with conventional surgery, vs. 10.9% with laparoscopic intervention
      (p < 0.05). The sample of patients with ASA 4-5 suffered a high mortality of
      82.7%. CONCLUSIONS: Laparoscopic closure of perforated ulcer is a safe
      therapeutic method, as confirmed by the results of many other studies around the
      world, which in many aspects favour the laparoscopic technique.

PMID- 25561997
TI  - Endoscopic third ventriculostomy - effectiveness of the procedure for obstructive
      hydrocephalus with different etiology in adults.
AB  - INTRODUCTION: After a time of domination of shunt placement, endoscopic third
      ventriculostomy (ETV) has been increasingly applied in treatment of obstructive
      hydrocephalus. AIM: To assess the effectiveness of ETV in treatment of adults
      with three-ventricle hydrocephalus of different etiology. MATERIAL AND METHODS:
      Ninety-six patients with obstructive hydrocephalus were studied: 24 with primary
      aqueductal stenosis, 61 with brain tumor, and 2 with basilar tip aneurysm. In 9
      patients the etiology of hydrocephalus remained undetermined. The assessment of
      treatment results was based on clinical and radiological criteria. RESULTS:
      Clinical improvement was observed in 74 (77.1%) patients, and radiological
      improvement in 52 (54.2%). One patient died. Follow-up of 24 patients with
      primary aqueductal stenosis has shown that in 20 (83.3%) of them clinical
      improvement has been stable, and in 14 (58.3%) radiological improvement has been
      observed. Two patients required shunt placement due to hydrocephalus recurrence
      12-24 months after the ETV procedure. Among 9 patients with undefined
      hydrocephalus, 3 required shunt placement within 6 months after ETV (2 shunted
      previously). Endoscopic third ventriculostomy treatment in a patient with
      hydrocephalus caused by basilar tip aneurysm succeeded. The assessment of ETV
      effectiveness in oncological patients has been indirect in view of the underlying
      disease. CONCLUSIONS: The best results of ETV treatment have been demonstrated
      for patients with primary aqueductal stenosis. Ventricle size cannot determine
      the effectiveness of treatment as an individual requirement. Endoscopic third
      ventriculostomy is effective in previously shunted patients although the
      prediction of outcome should be cautious. Endoscopic third ventriculostomy
      enables preparation for further therapy and is palliative treatment in
      oncological patients with secondary hydrocephalus.

PMID- 25561998
TI  - Laparoendoscopic single-site surgery adrenalectomy - own experience and matched
      case-control study with standard laparoscopic adrenalectomy.
AB  - INTRODUCTION: At our institution, laparoendoscopic single-site surgery (LESS) has
      been established as a technique for laparoscopic nephrectomy since 2011, and
      since 2012 in selected cases for adrenalectomy (AE) as well. AIM: To compare LESS
      AE with standard laparoscopic AE (SLAE). MATERIAL AND METHODS: Between 3/2012 and
      7/2014, 35 adrenalectomies were performed. In 18 (51.4%), a LESS approach was
      chosen. Indications were strictly non-complicated cases (body mass index (BMI) <
      34 kg/m(2), tumour <= 7 cm, non-malignant aetiology, no previous surgery). All
      LESS procedures were done by one surgeon. Standard equipment was a 10 mm rigid 0
      degrees  camera, Triport+, one pre-bent grasper, and a sealing instrument. The
      approach was pararectal in all cases except one (transumbilical in a slim man).
      Three patients with LESS were excluded (2 partial AEs only, one adrenal cancer
      converted to SLAE and then to open surgery). These 15 LESS AE procedures were
      compared to 15 SLAEs with similar characteristics chosen among 54 SLAEs performed
      in the period 1/2008-2/2012. RESULTS: In 8 cases (53.3%) of LESS AE, a 3 mm port
      was added to elevate the liver/spleen. Mean parameters of LESS AE vs. SLAE
      (Wilcoxon test): maximal tumour diameter 43.7 mm vs. 36.1 mm (p = 0.28), time of
      surgery 63.3 min vs. 55.3 min (p = 0.22), blood loss 38.0 ml vs. 38.0 ml (p =
      0.38), BMI 26.9 kg/m(2) vs. 28.5 kg/m(2) (p = 0.13), discharge from hospital 5.4
      days vs. 3.9 days (p = 0.038). There were no complications in either group.
      CONCLUSIONS: The LESS AE is feasible in selected cases, especially small left
      sided tumours in thin patients with no history of previous abdominal operations,
      but requires an additional port in half of the cases.

PMID- 25561999
TI  - Transanal endoscopic microsurgery for early rectal cancer: single center
      experience.
AB  - INTRODUCTION: The use of transanal endoscopic microsurgery (TEM) is increasing
      due to the ability to perform minimally invasive local treatment with large full
      thickness local excision under improved vision. AIM: To evaluate the initial
      experience with TEM for early rectal cancer in a single center. MATERIAL AND
      METHODS: From February 2010 to November 2013 a total of 20 patients underwent TEM
      for early rectal cancer. Nine were women and 11 men, age range 39 to 88 years
      (median: 71 years). The postoperative surveillance protocol, which includes rigid
      proctoscopy, carcinoembryonic antigen (CEA) and endorectal ultrasound every 3
      months during the first 2 years, was applied to all patients after TEM. RESULTS:
      Final histology revealed 14 (70%) lesions to be T1 and 6 (30%) T2 cancers. There
      were no postoperative complications. All 6 patients in the pT2 group and those in
      the pT1 group with unfavorable histology were offered adjuvant chemoradiotherapy
      or immediate radical surgery. Patients were followed up from 2 to 35 months
      (median: 21 months). There was one local recurrence (5%) in a patient who refused
      to undergo abdominoperineal excision for T1 low rectal cancer, had unfavorable
      histology after TEM, and for which reason underwent postoperative chemoradiation.
      The patient had abdominoperineal resection 7 months after TEM (rpT2N0M0). One
      patient was lost to follow-up. The rest of the patients are alive and disease
      free. CONCLUSIONS: In our hands, TEM was an alternative to total mesorectal
      excision in patients with low-risk early rectal cancer. Further follow-up is
      necessary to evaluate recurrence and survival rates after TEM for patients with
      invasive rectal cancer.

PMID- 25562000
TI  - A risk score to predict the difficulty of elective laparoscopic cholecystectomy.
AB  - INTRODUCTION: Several preoperative scoring systems have been proposed to predict
      the difficulty of laparoscopic cholecystectomy in order to optimize the results
      of surgical treatment by either selection of patients for the procedure or
      providing an adequately experienced surgical team for a given patient.
      Nevertheless, none of them has achieved significant penetration into everyday
      practice. AIM: To propose and validate a novel risk score based on the patient's
      history, physical examination and abdominal ultrasonography parameters. MATERIAL
      AND METHODS: The risk score was defined by the presence of the following risk
      factors: male sex, biliary colic within the last 3 weeks prior to surgery,
      history of acute cholecystitis treated conservatively, previous upper abdominal
      surgery, right upper quadrant pain, rigidity in right upper abdomen and
      ultrasonographic parameters - thickening of the gallbladder wall >= 4 mm,
      hydropic gallbladder (diameter exceeding 4.5 cm) and shrunken gallbladder. One
      point was allocated for each risk factor, except for previous upper abdominal
      surgery, which scored two. Difficulty of the surgery was assessed by operating
      time (OT) and the postoperative subjective evaluation score (PSES). RESULTS: Five
      hundred and eighty-six consecutive patients were enrolled in the prospective
      observational study. A significant linear correlation was observed between the
      risk score and measures of difficulty employed. Five levels of difficulty were
      defined (score 0, 1, 2, 3, >= 4) with significant differences in OT, PSES and
      conversion rates (p < 0.001). CONCLUSIONS: The suggested risk score is designed
      as a simple and reliable predictive model, possibly effective to overcome the
      negative effect of the individual proficiency gain curve and/or to select 'easy'
      cases for day surgery, single incision laparoscopic surgery or natural orifice
      translumenal endoscopic surgery procedures.

PMID- 25562001
TI  - Integrated image navigation system using head-mounted display in "RoboSurgeon"
      endoscopic radical prostatectomy.
AB  - The safety and efficacy of minimally invasive surgery relies on visual
      information. We aimed to develop an integrated image navigation system
      (RoboSurgeon System) that combines head-mounted displays (HMDs) with multiple
      image modalities, and assessed its feasibility in 5 prostate cancer patients who
      underwent gasless single-port endoscopic radical prostatectomy. A robotically
      manipulated transrectal ultrasound (TRUS) system was used. In all cases,
      preoperative magnetic resonance (MR) images and intraoperative real-time images
      of an endoscope, TRUS, and HMD-mounted camera were integrated and displayed
      synchronously on each HMD in a four-split screen mode during the entire process.
      The TRUS helped identify the boundary with the adjacent structures endoscopically
      in reference to MR images. There were no negative incidents in intraoperative or
      postoperative courses. Integrated image navigation using HMDs as individualized
      monitors is feasible in the natural ergonomic position and may be beneficial to
      identify correct dissection planes. The efficacy of the RoboSurgeon System
      deserves further evaluation. 

PMID- 25562002
TI  - A simple technique for evacuating air bubbles with scum from the bladder dome
      during transurethral resection of bladder tumor.
AB  - Air bubbles floating in the bladder dome during transurethral resection of a
      bladder tumor can interfere with the resection, causing intravesical explosion
      and increasing the potential risk of tumor cell reimplantation. We describe a
      simple and effective technique for evacuating air bubbles from the bladder dome
      using routine resectoscopes. First, the beak of the resectoscope is positioned
      near the air bubble in the bladder dome. Second, the drainage channel of the
      resectoscope is closed. Third, the irrigation tube is detached from the
      irrigation channel, and then the channel is opened. Subsequently, the air bubble
      with entangled scum will be retrogradely aspirated from the beak of the
      resectoscope to the irrigation channel. Reversing the direction of the water
      stream enables evacuation of the air bubble with the scum under direct vision.
      This simple and effective technique may assist surgeons and ensure the safety of
      patients during a transurethral procedure. 

PMID- 25562003
TI  - Large inflammatory fibroid polyp of cardia managed laparoscopically - a case
      report and review of the literature.
AB  - Inflammatory fibroid polyp or Vanek's tumor of the gastrointestinal tract is a
      rare, benign neoplasm. The lesion may occur at any age but is commonest in the
      sixth and seventh decades and is more often found in women. It is mostly situated
      in the stomach, especially in the antrum. Symptoms depend on the location and the
      size of the lesion. We present a case of a 67-year-old woman with a large
      inflammatory polyp of the cardia with a diameter of 10 cm * 5.5 cm * 7.5 cm
      imitating gastrointestinal stromal tumor (GIST). The patient complained of
      abdominal pain, nausea and mild anemia. We performed laparoscopic topical
      excision of the tumor. The postoperative course was uneventful. The 6-month
      follow-up did not reveal recurrence. The clinical image of a large Vanek's tumor
      can imitate symptoms of gastric cancer or GIST. Topical laparoscopic excision
      with a 1-2 cm healthy wall margin is a sufficient and adequate way of treatment. 

PMID- 25562004
TI  - The DIAMOND system in the treatment of type 2 diabetes mellitus in an obese
      patient.
AB  - Obesity and type 2 diabetes mellitus have reached epidemic proportions worldwide.
      As the majority of antidiabetic medications are of limited efficacy and patient
      adherence to long-term therapy is one of the main limiting factors of effective
      blood glucose and body weight control, new therapies are still looked for. The
      DIAMOND system seems to be one of the most promising among them. This system
      recognizes natural electrical activity of the stomach and automatically applies
      electrical stimulation treatment during/after eating with subsequent modulation
      of signals transmitted to the regulatory centers in the brain in order to provoke
      an early response of the gut typical of a full meal. We present the case of a 47
      year-old obese woman with type 2 diabetes. During treatment with this system,
      serum glucose and hemoglobin A1c levels significantly decreased. Body weight loss
      and waist circumference reduction were observed. Additionally, beneficial effect
      on lipid profile was found. 

PMID- 25562005
TI  - Single incision laparoscopic splenectomy, technical aspects and feasibility
      considerations.
AB  - Minimally invasive techniques have been introduced to reduce morbidity related to
      standard laparoscopic procedures. One such approach is laparoendoscopic single
      site surgery. The aim of the study was to present our initial clinical experience
      of using this technique for elective splenectomy. We carried out single access
      laparoscopic splenectomy (SALS) for an 8 cm cystic lesion of the spleen,
      involving the hilum, on a 38-year-old woman. The procedure was performed with a
      single-port device (4-channel) via a 2.5-cm umbilical incision. A flexible 5-mm
      optic and straight laparoscopic instruments were used. The operative time was 75
      min. There was no blood loss. No complications were observed. The postoperative
      period was uneventful. Although substantial development of the instruments and
      skills is needed, this SALS technique appears to be feasible and safe.
      Nevertheless, further experience and observations are necessary. 

PMID- 25562006
TI  - Integrated image monitoring system using head-mounted display for gasless single
      port clampless partial nephrectomy.
AB  - A novel head-mounted display (HMD) offers a higher quality of endoscopic imagery
      in front of the eyes regardless of head position. We present an application of
      the HMD system as a personal integrated multi-image monitoring system in gasless
      single-port clampless partial nephrectomy (PN). Our HMD system displayed multiple
      forms of information as integrated, sharp, high-contrast images both seamlessly
      and synchronously using a four-split screen. The surgeon wearing an HMD display
      could continuously and simultaneously monitor the endoscopic, three-dimensional
      (3D) video and intraoperative ultrasound images. In addition, the operator can
      rotate the 3D video image using fingertip movements on the finger tracking
      system. All two clampless partial nephrectomies were safely completed within the
      operative time, blood loss was within usual limits and there were no
      complications. The integrated image HMD system might facilitate maneuverability
      and safety in minimally invasive clampless PN. 

PMID- 25562007
TI  - A three-dimensional head-mounted display system (RoboSurgeon system) for gasless
      laparoendoscopic single-port partial cystectomy.
AB  - We developed a new three-dimensional (3D) head-mounted display (HMD) system
      (RoboSurgeon system) that combines a high-definition 3D organic
      electroluminescent HMD with a high-definition 3D endoscope and applies it to
      minimally invasive surgery. This system presents the surgeon with a higher
      quality of magnified 3D imagery in front of the eyes, regardless of head
      position. We report 5 cases of RoboSurgeon gasless laparoendoscopic single-port
      partial cystectomy, which is carried out as part of our selective bladder-sparing
      protocol, with a technique utilizing both an intravesical and extravesical
      approach. While carrying out the surgery, the system provides the surgeon with
      both excellent 3D imagery of the operative field and clear imagery of the
      cystoscopy. All procedures were safely completed and there were no complications
      except for a case of postoperative lymphorrhea. Our experience shows that the 3D
      HMD system might facilitate maneuverability and safety in various minimally
      invasive procedures. 

PMID- 25562008
TI  - A head-mounted display-based personal integrated-image monitoring system for
      transurethral resection of the prostate.
AB  - The head-mounted display (HMD) is a new image monitoring system. We developed the
      Personal Integrated-image Monitoring System (PIM System) using the HMD (HMZ-T2,
      Sony Corporation, Tokyo, Japan) in combination with video splitters and
      multiplexers as a surgical guide system for transurethral resection of the
      prostate (TURP). The imaging information obtained from the cystoscope, the
      transurethral ultrasonography (TRUS), the video camera attached to the HMD, and
      the patient's vital signs monitor were split and integrated by the PIM System and
      a composite image was displayed by the HMD using a four-split screen technique.
      Wearing the HMD, the lead surgeon and the assistant could simultaneously and
      continuously monitor the same information displayed by the HMD in an
      ergonomically efficient posture. Each participant could independently rearrange
      the images comprising the composite image depending on the engaging step. Two
      benign prostatic hyperplasia (BPH) patients underwent TURP performed by surgeons
      guided with this system. In both cases, the TURP procedure was successfully
      performed, and their postoperative clinical courses had no remarkable unfavorable
      events. During the procedure, none of the participants experienced any HMD-wear
      related adverse effects or reported any discomfort. 

PMID- 25562010
TI  - Laparoscopic management of adnexal torsion in a twin, in vitro fertilization
      pregnancy at 23 weeks.
AB  - Maternal adnexal torsion in pregnancy, with a reported incidence of 1-10 per
      10,000 spontaneous pregnancies, is very uncommon. Since it has been described as
      a severe complication after controlled ovarian hyper-stimulation for in vitro
      fertilization (IVF), it is more common in IVF pregnancies. This condition mainly
      occurs in the first trimester; it is rare during the late second trimester.
      Conservative management of adnexal torsion by laparoscopy is extended for the
      management of such conditions during pregnancy. An enlarged uterus could cause
      operational difficulties in the second trimester. In this paper, we report a case
      of adnexal torsion in a twin, 23 weeks with IVF pregnancy, that was successfully
      untwisted by laparoscopy. 

PMID- 25562009
TI  - Laparoscopic robotic total gastrectomy.
AB  - Minimally invasive gastrectomy has become the standard of care in many centers in
      Asia but remains unpopular in Europe. The aim of this article is to present the
      technique of laparoscopic robot-assisted total gastrectomy. The presented case
      involved a 66-year-old female patient with an advanced gastric cancer on the
      lesser curvature of the stomach. The laparoscopic part of the procedure involved
      opening the lesser sac, mobilization of the greater curvature and transection of
      the duodenum. A robot was used for the D2 lymphadenectomy and creation of the
      anastomosis. In summary, we have found that during a total gastrectomy for
      advanced gastric cancer a successful oncological resection can be achieved using
      a minimally invasive approach. We have also found that by combining conventional
      laparoscopy with robotic assistance we could overcome the technical difficulties
      with regards to lymph node dissection and anastomosis. 

PMID- 25562011
TI  - Inflammatory myofibroblastic tumour in a 5-year-old child - a case report and
      review of the literature.
AB  - Inflammatory myofibroblastic tumour is an uncommon tumour of intermediate
      malignant potential. Its aetiology is still unclear. It occurs predominantly in
      children and young adults. This report presents a case of pulmonary inflammatory
      myofibroblastic tumour in a 5-year-old girl. The patient had a history of
      recurrent respiratory tract infections. A chest radiograph and computed
      tomography chest scan showed a round mass in the lower lobe of her left lung.
      Thoracoscopic marginal excision of the tumour with an Endo-GIA stapler device
      (TYCO healthcare) was performed. Histological examination confirmed the final
      diagnosis of inflammatory myofibroblastic tumour. Postoperative recovery was
      uncomplicated and the patient was discharged 6 days after surgery. Round masses
      located in the lungs are very rare in children and the possibility of
      myofibroblastic tumour as well as metastatic lesions should be taken into
      consideration in such cases. Thoracoscopic excision is the best option in
      distally located lesions. 

PMID- 25562012
TI  - Nutritional optic neuropathy following bariatric surgery.
AB  - Bariatric procedures, associated with gastrointestinal malabsorption of vitamins
      and microelements, may constitute a risk factor for nutritional optic neuropathy
      (NON). We present a case of a 34-year-old female patient who developed bilateral
      NON after sleeve gastrectomy. Despite postoperative ophthalmological supervision,
      10 months after the procedure the woman presented with a bilateral decrease in
      visual acuity down to 0.8, bilateral visual field loss and abnormal visual evoked
      potential recordings. Laboratory abnormalities included decreased serum
      concentration of vitamin B12 (161 pg/ml). Treatment was based on intramuscular
      injections of vitamin B12 (1000 units per day). After 1 week of the treatment, we
      observed more than a three-fold increase in the serum concentration of vitamin
      B12 and resolution of the bilateral symptoms of NON. The incidence of NON is
      likely to increase due to the growing number of these bariatric procedures
      performed worldwide. Therefore, all persons subjected to such surgery should
      receive long-term ophthalmological follow-up and supplementation with vitamins
      and microelements. 

PMID- 25562013
TI  - Diagnosis and treatment of a patient with type IV endoleak as a late complication
      after endovascular aneurysm repair.
AB  - Type IV endoleak is a very rare complication observed after implantation of
      aortobiiliac stent grafts. The difficult diagnosis of type IV endoleak leads to
      the application of many imaging methods in the diagnostic process. We present a
      case report of a patient who underwent implantation of an aortobiiliac stent
      graft in 2004. After surgery, the size of the aneurysm sac was monitored
      continually in the subsequent imaging studies. Progression of the aneurysm sac
      volume was detected in 2009. In a short period of time, the diameter of the
      aneurysm increased from 100 to 140 mm. Angio-computed tomography and angiography
      did not reveal the location of the endoleak. The attempt at localization and
      endovascular closure of the source of the endoleak failed. It was decided to
      treat the patient surgically. Intraoperatively, the source of the endoleak was
      visualized, and the endoleak was closed with surgical sutures. 

PMID- 25562015
TI  - Autonomy of children and adolescents in consent to treatment: ethical,
      jurisprudential and legal considerations.
AB  - Autonomy is usually considered as a main principle in making decisions about
      individuals' health. Children and particularly adolescents have the capacity to
      take part in medical decision-making to some extent. For the most part the parent
      doctor-child/adolescent triangle sides are essentially in agreement, but this may
      not be true in some cases, causing physicians to face problems attempting to
      determine their professional duties. According to Islamic jurisprudent upon
      reaching the age of Taklif (15 full lunar years for boys and 9 full lunar years
      for girls) no one can be treated as incompetent based on mental immaturity unless
      his or her insanity or mental immaturity is provend Moreover the Islamic Sharia,
      decrees that parents should lose their authority to make medical decisions for
      their children, if their bad faith or imprudence is proven, in which case a fit
      and proper person or an institution will be appointed to make decisions in this
      respect based on the child's best interests. 

PMID- 25562014
TI  - Periodic Fever: A Review on Clinical, Management and Guideline for Iranian
      Patients - Part II.
AB  - Periodic fever syndromes are a group of diseases characterized by episodes of
      fever with healthy intervals between febrile episodes. In the first part of this
      paper, we presented a guideline for approaching patients with periodic fever and
      reviewed two common disorders with periodic fever in Iranian patients including
      familial Mediterranean fever (FMF) and periodic fever syndromes except for
      periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA).
      In this part, we review other autoinflammatory disorders including hyper IgD,
      tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrin
      associated periodic syndromes, autoinflammatory bone disorders and some other
      rare autoinflammatory disorders such as Sweet's and Blau syndromes. In cryopyrin
      associated periodic syndromes group, we discussed chronic infantile neurologic
      cutaneous and articular (CINCA) syndrome, Muckle-Wells syndrome and familial cold
      autoinflammatory syndrome. Autoinflammatory bone disorders are categorized to
      monogenic disorders such as pyogenic arthritis, pyoderma ;gangraenosum and acne
      (PAPA) syndrome, the deficiency of interleukine-1 receptor antagonist (DIRA) and
      Majeed syndrome and polygenic background or sporadic group such as chronic
      recurrent multifocal osteomyelitis (CRMO) or synovitis, acne, pustulosis,
      hyperostosis and osteitis (SAPHO) syndrome are classified in sporadic group.
      Other autoinflammatory syndromes are rare causes of periodic fever in Iranian
      system registry. 

PMID- 25562016
TI  - The Association between Carotid Intima-Media Thickness and the Duration of Type 1
      Diabetes in Children.
AB  - OBJECTIVE: Carotid intima-media thickness (cIMT) has been known as a criterion of
      generalized atherosclerosis and a marker of cardiovascular disease progression in
      many studies which can be measured by ultrasound using high-resolution device.
      METHODS: This is a case-control study. A total of 40 children (16 males and 24
      females) with type1 diabetes mellitus and control group consisting of equal
      numbers (17 males and 23 females) who were otherwise healthy were included in the
      study from May 2007 to January 2008. The two groups were age matched, with the
      mean age of 10.56+/-3.21 years in control group and 10.67+/-4.18 years in
      diabetic patients. Left and right cIMT were measured by ultrasound. Findings :
      There was a significant difference between case and control subjects in terms of
      mean cIMT (P<0.001). cIMT was significantly higher in the diabetic group. Among
      variables including age, BMI and diabetes, diabetes was the only influential
      parameter in this respect. The mean time length of type 1 diabetes in our
      diabetic group was reported 4.24+/-3.02 years, with a minimum of four months and
      a maximum of ten years. There was a statistically significant difference between
      the two diabetic patients with below and above four years of disease duration
      (P=0.03 for right carotid artery and P=0.01 for left carotid artery). CONCLUSION:
      cIMT has been identified as an early indicator of atherosclerosis in many
      studies. It increases in patients with type 1 diabetes as the disease progresses
      and this can be followed by macro and microvascular atherosclerotic changes.

PMID- 25562017
TI  - What has national screening program changed in cases with congenital
      hypothyroidism?
AB  - OBJECTIVE: Since congenital hypothyroidism (CH) is the most important cause of
      preventable mental retardation, its screening is important. In this present
      study, it was aimed to evaluate congenital hypothyroidism cases before and after
      the initiation of screening program in year 2007 in our country. METHODS: A total
      of 400 patients diagnosed with CH at our outpatient clinic were retrospectively
      evaluated. Age of diagnosis, complaint, clinical signs, and etiological
      distribution were detected and changes in those parameters were evaluated before
      and after year 2007, which was the initiation date of our national screening
      program. Findings : After year 2007, 70.6% of patients were diagnosed in the
      first month; 21.2% in 1-3 months; 6.5% in 3-6 months, and no patient was
      diagnosed after 9 months. Before initiation of the screening program, 48.4% of
      cases were diagnosed in the first month, the percentage was increased to 62.8%
      after the program; the increase was significant. While mental retardation was
      detected in 13.3% of patients before the screening, it was decreased to 4% after
      initiation of the program. An interesting finding was that age of treatment onset
      in girls was significantly higher than in boys before the screening; there was no
      difference between them after initiation of the screening. CONCLUSION: In this
      present study, it was observed that ages of diagnosis and treatment as well as
      mental retardation rates were significantly decreased in girls after the
      screening program, but ideal results have not been reached yet, and is expected
      to be reached in the future.

PMID- 25562018
TI  - Isolation and Identification of E. cowanii from Powdered Infant Formula in NICU
      and Determination of Antimicrobial Susceptibility of Isolates.
AB  - OBJECTIVE: Enterobacter cowanii is a genus of common gram-negative, facultatively
      anaerobic, rod-shaped, non-spore-forming bacterium of the Enterobacteriaceae
      family. This organism can be potentially a powdered infant milk formula-borne
      opportunistic pathogen. The aim of this study was to isolate and identify E.
      cowanii from consumed powdered infant formula milk (PIF) in intensive care units
      (NICU) and to determine antimicrobial susceptibility patterns of this bacterium.
      METHODS: E. cowanii was isolated according to FDA method in 125 samples of PIF
      milk purchased from drug stores between Jun 2011 and March 2012. For final
      confirmation, biochemical tests embedded in API-20E system were used. The drug
      susceptibility test was performed using the disc diffusion method according to
      CLSI recommendations. Findings : Out of the 125 PIF samples investigated, 4
      (3.2%) samples were positive for E. cowanii. All four isolates from PIF samples
      were uniformly susceptible to imipenem, meropenem, ceftazidime, ciprofloxacin,
      and colistin. Fifty percent of isolates were resistant to ampicillin,
      amoxicillin, and cotrimoxazole Conclusion: Analysis of the results indicated that
      complementary studies are necessary to clarify the possible role of E. cowanii as
      a food contaminant, in common NICU infections and high risk groups including
      persons with underlying disease and immunocompromised individuals.

PMID- 25562019
TI  - Blood eosinophil levels in newborns with severe indirect hyperbilirubinemia
      treated with phototherapy.
AB  - OBJECTIVE: Newborns who suffer from jaundice and/or receive phototherapy (PT) are
      at a higher risk of developing asthma. In this study we aimed to investigate the
      relationship between bilirubin and peripheral eosinophil counts in newborns with
      severe hyperbilirubinemia needing PT. METHODS: In this study, a retrospective
      analysis was performed on 306 newborns with severe hyperbilirubinemia with
      gestational age >=35 weeks (Group 1) and the control group consisted of 295 age
      and gender-matched newborns (Group 2). Total serum bilirubin, hemoglobin,
      albumin, leucocyte and eosinophil counts before and after PT were recorded from
      medical charts. Findings : All the patients in Group 1 received phototherapy and
      77 (25.2%) of them needed exchange transfusion (ET). Before receiving PT, the
      patients in Group 1 had lower levels of Hb and higher levels of total serum
      bilirubin and lymphocytes than those in Group 2 although there was no
      statistically significant difference with regard to peripheral eosinophil counts.
      Eosinophils were detected to be numerically lower in Group 1. Higher bilirubin
      subgroups had also lower eosinophil counts. The patients in Group 1 had lower
      levels of Hb, leucocyte, albumin and higher levels of eosinophil following PT.
      CONCLUSION: Peripheral eosinophil count may be affected by bilirubin levels
      and/or phototherapy. There is a need for further clinical research based on
      different models.

PMID- 25562020
TI  - The effect of malnutrition on protein glycosylation in children.
AB  - OBJECTIVE: The goal of this study was to evaluate the effect of protein energy
      malnutrition on protein glycosylation by investigating transferrin isoform
      pattern and its relationship to the degree of malnutrition and the biochemical
      markers of nutritional status in children. METHODS: Forty one children with mild
      (n=23) and severely/moderately (n=18) acute malnutrition and 29 controls were
      enrolled in the study. Serum transferrin isoforms were determined by isoelectric
      focusing electrophoresis. Transferrin, prealbumin, zinc, iron and insulin-like
      growth factor-1 (IGF-1) were measured using automated analyzers. Findings :
      Asialotransferrin and disialotransferrin were significantly higher in
      severely/moderately malnourished patients compared to controls (P=0.04 and
      P=0.04, respectively). Other transferrin isoform patterns were not different
      among three groups. Serum IGF-1, transferrin and iron levels of severely/
      moderately malnourished group were significantly lower than tose of controls
      (P=0.001, 0.02 and 0.03, respectively). Serum prealbumin and zinc levels were
      similar in all three groups. Serum IGF-1, transferrin and iron levels, and all
      transferrin isoform patterns were not significantly different in mildly
      malnutrition group from other two groups. CONCLUSION: The changes in transferrin
      isoform pattern observed in malnourished patients may indicate that malnutrition
      is a catabolic state which has effects on glycosylation.

PMID- 25562021
TI  - Prevalence of celiac disease in Turkish children with idiopathic epilepsy.
AB  - OBJECTIVE: This study has examined the prevalence of celiac disease in Turkish
      children with idiopathic epilepsy. METHODS: Children with idiopathic epilepsy
      were screened for celiac disease using the IgA anti-tissue transglutaminase
      antibody and compared with the healthy control group in order to find the
      association of celiac disease (CD) with idiopathic epilepsy. Upper
      gastrointestinal endoscopy and small intestinal biopsies were offered to all
      antibody-positive patients. Findings : A total of 214 children with the diagnosis
      of idiopathic epilepsy and 166 healthy children as control group were studied. Of
      the patients recruited, 55.1% had generalized epilepsy, and 44.9% had partial
      epilepsy. In 33 patients with partial epilepsy, electroclinical features were
      consistent with a diagnosis of childhood partial epilepsy with occipital
      paroxysms (CPEO). Two of 33 patients with CPEO had positive IgA anti-tissue
      transglutaminase antibodies in serology. Pathological examination of small
      intestinal biopsy specimens showed total villous atrophy in both of them. The
      prevalence of celiac disease among children with idiopathic epilepsy and CPEO was
      0.9% and 6%, respectively. CONCLUSION: The results of the present study revealed
      that prevalence of CD is increased in children with epilepsy. On the other hand,
      as high as 6% prevalence of CD among patients with CPEO found in this study
      should be kept in mind and the clinicians should be aware of this association.

PMID- 25562022
TI  - The effects of decreasing maternal anxiety on fetal oxygenation and nucleated red
      blood cells count in the cord blood.
AB  - OBJECTIVE: Vasoconstriction during anxiety reduces fetal oxygenation and leads to
      hypoxia. Hypoxia in turn results in increase of the number of nucleated red blood
      cells (NRBCs) in the cord blood. The present study aimed to assess the effect of
      decreasing maternal anxiety on fetal oxygenation and NRBCs count in the cord
      blood. METHODS: . In this study, 150 women were randomly divided into two
      intervention groups [supportive care and acupressure in BL32 (bladder) acupoint]
      and a control group (hospital routine care). The infants' cord blood was
      investigated regarding the number of NRBCs and the intensity of hypoxia after
      birth. Then, the data were entered into the SPSS statistical software (v. 16) and
      analyzed using ANOVA, Chi-square test, and logistic regression analysis. Findings
      : The significant difference was found between the two groups regarding the
      number of NRBCs counted in the peripheral blood smear (P<0.001). Besides, a
      significant relationship was observed between the length of the first and second
      stages of labor and the number of NRBCs in the cord blood (P=0.01). Also, a
      significant association was observed between the type of delivery and the number
      of NRBCs in the cord blood in both intervention (P<0.001) and control groups
      (P=0.03). CONCLUSION: Doula supportive care and acupressure at BL32 point reduced
      the length of labor stages as well as the anxiety level. Also, nucleated red
      blood cells were less in the 2 groups of intervention than in control group.
      Regarding the fact that nucleated red blood cells cannot be the only factor for
      hypoxia predicting, for affirmation of this theory study with higher sample size
      and survey of mothers at high risk are needed.

PMID- 25562023
TI  - Effect of pubertal suppression on linear growth and body mass index; a two-year
      follow-up in girls with genetic short stature and rapidly progressive puberty.
AB  - OBJECTIVE: Gonadotropin-Releasing Hormone agonists (GnRHa) are used to improve
      the final adult height in short stature children. There are limited studies which
      address the potential side effect of these agents: excessive weight gain. We have
      followed girls with rapidly progressive puberty receiving GnRHa and results were
      focused on the effect of treatment on final height, weight and body mass index
      Methods: Thirty girls between 8.5 and 12 years with short stature and predicted
      adult height of less than 155 cm were enrolled in the study. All had rapidly
      progressive puberty. Weight and height measurements were done at the beginning of
      treatment, 6 and 12 months after starting and 6 and 12 months after the cessation
      of treatment. Bone age and stages of puberty were estimated at the beginning of
      treatment, after 12 months of starting and 12 months after the treatment was
      stopped. Findings : Predicted adult height (PAH) changes during treatment were
      not significant. There was no significant difference between final height and
      weight according to the body mass index (BMI), PAH or bone age. CONCLUSION: We
      conclude that girls with genetic short stature and rapidly progressive puberty
      will not benefit receiving a one-year course of GnRHa and there is no significant
      difference between the final height and final weigh among children according to
      BMI.

PMID- 25562024
TI  - Clinical and Neuroimaging Findings of Sydenham's Chorea.
AB  - OBJECTIVE: Sydenham's chorea (SC) is thought to be an autoimmune disorder. MRI is
      generally used to exclude other causes of chorea. There are no typically defined
      MRI features of SC. In this study we aimed to determine clinical and neuroimaging
      findings of SC. METHODS: In this study 17 patients with acute SC were
      retrospectively evaluated. Sydenham's chorea was diagnosed according to the 1992
      revision of the Jones criteria. The other causes of chorea were excluded. Cranial
      MRI was performed in all patients during the acute phase of SC. Walking, speech
      and swallowing disorders, muscle weakness, behavioral disorders, treatment,
      symptom recovery time and recurrence were evaluated. Findings : The patients'
      mean age was 11.2 years. Behavioral changes, muscle weakness and dysphagia
      occurred in 70%, 64% and 23% of the patients, respectively. Nonspecific signal
      hyperintensities were observed in the white matter, brain stem and caudate
      nucleus in 47% of patients. Two patients who had chorea paralytica were treated
      successfully with a high dose of intravenous methylprednisolone. CONCLUSION:
      Nonspecific hyperintense white matter abnormalities may be due to the
      inflammatory process associated with a longer duration of clinical signs. To
      explain the MRI findings and the pathogenesis of SC, comprehensive studies are
      needed.

PMID- 25562025
TI  - Orofacial pathologic lesions in children and adolescents: a clinicopathological
      study in southern iran.
AB  - OBJECTIVE: Oral and maxillofacial lesions vary regarding their clinical
      presentation in different populations. Until now, oral and maxillofacial lesions
      in Iranian children and adolescents have not been studied. The aim of this study
      was to determine the type and distribution of biopsied oral lesions among
      children and adolescents in Southern Iran. METHODS: All the patients referred to
      the pathology department of Shiraz Faculty of Dentistry from 1991-2009 were
      enrolled in this retrospective, case-series study. The information regarding the
      patients' age, gender as well as the histopathologic type and anatomic location
      of the biopsied oral lesions in patients under 18 years was collected from
      patients' medical documents and were analyzed by SPSS version 11. Findings : Out
      of 2984 patients, 576 (19.3 %) cases were children and adolescents under 18
      years. The most prevalent category was soft tissue lesions (45.5 %). The most
      common lesion was peripheral giant cell granuloma (15.6%) followed by dentigerous
      cyst (14.2%) and pyogenic granuloma (11.3%). Gingiva was the most common affected
      site. Male to female ratio was 1.2. CONCLUSION: Our results revealed that near
      20% of orofacial lesions occur in children and adolescents with rather equal male
      to female ratio. The majority of lesions were soft tissue diseases with a
      reactive nature. Unlike other studies we had higher rates of soft tissue lesions.
      These data can help dentists and surgeons for more accurate management of their
      patients.

PMID- 25562026
TI  - Prepregnancy Maternal Weight and Body Mass Index of Children with and without
      Congenital Heart Disease.
AB  - OBJECTIVE: Congenital heart diseases are among the most frequent major congenital
      anomalies. One of the suspected reasons for congenital heart defects is
      overweight and obesity of mother during prepregnancy and pregnancy. We studied
      the relationship between maternal overweight and obesity and the risk of
      congenital anomaly. METHODS: All of children with congenital heart defect (164
      infants with major nonsyndromic heart disease) referred to our pediatric
      cardiology clinic or admitted to our ward during 2011-2012 were included in this
      study. Controls were 158 live-born infants without any major malformations and
      their mothers. Mothers of these infants were studied for weight, height and body
      mass index (BMI). Findings : The most frequent congenital heart disease was
      ventricular septal defect (39%), patent ductus arteriosus (11%), complete
      atrioventricular septal defect (10%), pulmonary stenosis (9.1%), and atrial
      septal defect (8.5%). There was no significant difference between maternal age
      (P=0.1), weight (P=0.8) and height (P=0.3) in the two groups. The mothers had not
      significantly higher BMI than that of the control mothers. Compared with
      underweight (BMI <18.5) and normal weight women (OR: 1.24, 95%CI: 0.40-3.89),
      overweight (OR: 0.98, 95%CI: 0.31-3.10) and obese women (OR: 1.16, 95%CI: 0.34
      4.00) were not more likely to have an infant with a congenital heart defect.
      CONCLUSION: This study suggests that there may not be a relation between maternal
      BMI and having a child with congenital heart defect.

PMID- 25562028
TI  - Treatment outcome of neurogenic bladder dysfunction in children; a five-year
      experience.
AB  - OBJECTIVE: A neurogenic bladder is one which functions abnormally due to
      disorders of sacral nerves that control the bladder's ability to fill, store and
      empty urine. Abnormal bladder function can cause the bladder to be underactive or
      overactive. This study was planned to evaluate the treatment outcome of our
      patients with neurogenic bladder dysfunction (NGBD). METHODS: Thirty three
      patients who have been treated for NGBD were evaluated. Diagnosis was confirmed
      by voiding-cysto-urethrography (VCUG) and urodynamic study. The patients were
      treated medically and all had clean intermittent catheterization (CIC). Data
      regarding age, sex, clinical and paraclinical findings, sonography, imagings,
      renal scan, associated anomalies, treatment and outcomes were collected and
      entered in SPSS software version18 and analyzed by descriptive statistical.
      Findings : Totally 33 patients aged three days to four years (mean 6.8 months)
      were included in this study. There were 20 (61%) males and 13 (39%) females. Mean
      follow-up period was 3.4+/-1.2 years (1.5 months to 5 years). Eighty two precent
      cases had bilatral and 18% unilatral hydronephrosis and bilatral vesicouretral
      reflux (VUR) existed in 67% and unilatral in 33% of the patients. Treatment
      consisted of antibiotherapy and CIC in all patients, which was only in 33% of the
      cases succesful. The most common associated anomaly was meningomyelocle in 8
      patients. Vesicostomy was performed in 22 (67%) cases. Kidney scan showed scar in
      10 patients at follow-up study. Complete continence on follow-up was achieved in
      24 (71% ) patients, and it was improved in 6 (18% ) cases. Mortality rate was 9%
      (3 cases). Cure rate was 85% in urinary tract infection, 82.7% in hydronephrosis,
      80% in VUR and 86.5% in kidney function. CONCLUSION: Anticholinergic medications
      was not effective in all our patients. We believe that permanent vesicostomy is
      an effective and acceptable surgical intervention for protection of upper urinary
      tract decompression, especially in those who do not respond to medical treatment
      and have high risk position.

PMID- 25562027
TI  - Absence of Association between -1131T>C Polymorphism in the Apolipoprotein APOA5
      Gene and Pediatric Metabolic Syndrome.
AB  - OBJECTIVE: In the present study, we evaluated the association of rs662799 variant
      of the APOA5 gene with Metabolic syndrome (MetS) in a sample of children and
      adolescents from Isfahan. METHODS: This case control study comprised 50 cases of
      MetS and 50 controls. Mismatched polymerase chain reaction-restriction fragment
      length polymorphism (mPCR-RFLP) was used to genotype -1131T>C polymorphism.
      Findings : No significant association was documented for APOA5 genotypes with the
      measured laboratory parameters for CC, CT, and TT genotypes in the two groups
      studied. By logistic regression using a dominant model, the odds ratio (95%
      confidence interval0 for the MetS was 0.38 (0.139-1.0350 and 0.29 (0.08-1.071 for
      the unadjusted and adjusted models, respectively. CONCLUSION: This study suggests
      that among studied children and adolescents, -1131T>C polymorphism in the APOA5
      gene may not be a major contributor to the MetS risk.

PMID- 25562029
TI  - Minimally invasive transthoracic device closure of an acquired sinus of valsalva
      right ventricle fistula in a pediatric patient.
AB  - BACKGROUND: Sinus of Valsalva-right ventricle fistula is a recognized but very
      rare complication after surgical repair of subaortic ventricular septal defect.
      Surgical repair with cardiopulmonary bypass and percutaneous transcatheter
      closure guided by x-ray has been the traditional treatment for fistula of sinus
      of Valsalva. CASE PRESENTATION: Recently, we have used a novel approach, that
      avoids the need for either secondary open surgical repair or radiation exposure;
      that is, minimally invasive transthoracic device closure guided by
      transesophageal echocardiography to occlude an acquired sinus of Valsalva-right
      ventricle fistula in a 4-year-old patient. CONCLUSION: To our knowledge, there
      have been no prior cases reported of this technique applied to close an acquired
      sinus of Valsalva-right ventricle fistula. This report aims to provide a detailed
      description of the procedure.

PMID- 25562030
TI  - Term infant with gallbladder stone: a case report.

PMID- 25562031
TI  - Leukoerythroblastosis Mimicking Leukemia: A case report.

PMID- 25562032
TI  - Association of juvenile idiopathic arthritis and digeorge syndrome; a case
      report.

PMID- 25562033
TI  - Accidents in children under 5 years in isfahan, iran.

PMID- 25562035
TI  - Aerobic exercise alleviates ischemia-induced memory impairment by enhancing cell
      proliferation and suppressing neuronal apoptosis in hippocampus.
AB  - PURPOSE: Neurogenic lower urinary tract dysfunction (NLUTD) is a possible
      consequence of several neurological disorders. NLUTD may produce debilitating
      symptoms and serious complications, such as chronic renal failure, and recurrent
      urinary tract infections. Many animal studies of NLUTD symptoms have focused on
      animal models of cerebral ischemia. In the present study, we investigated the
      effects of treadmill exercise on memory function and its relation to cell
      proliferation and apoptosis in the hippocampus, following transient global
      ischemia in gerbils. METHODS: To induce transient global ischemia in gerbil, both
      common carotid arteries were occluded for 5 minutes. Gerbils in the exercise
      groups were forced to run on a treadmill exercise for 30 minutes once a day for 2
      weeks. Step-down avoidance task and Y maze task were performed. Terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-staining,
      immunohistochemistry for 5-bromo-2'-deoxyridine, doublecortin, caspase-3, and
      Western blot for brain-derived neurotrophic factor (BDNF), Bax, Bcl-2, cytochrome
      c, caspase-3 were conducted. RESULTS: Ischemia caused memory impairment with an
      increase of cell proliferation, BDNF expression, and apoptosis in the
      hippocampus. Treadmill exercise improved memory function with further increase of
      cell proliferation and BDNF expression and a decrease of apoptosis. CONCLUSIONS:
      The animal model that we have developed and our assessment of the relation
      between exercise and brain function can be useful tools for future investigations
      of NLUTD symptoms associated with stroke, particularly ischemic stroke. The
      present study suggests that treadmill exercise promoted the recovery of brain
      function after cerebral ischemia.

PMID- 25562034
TI  - Necessity of amoxicillin clavulanic acid in addition to prednisolone in mild-to
      moderate COPD exacerbations.
AB  - BACKGROUND: The effectiveness of antibiotics in chronic obstructive pulmonary
      disease (COPD) exacerbations is still a matter of debate, especially in
      outpatients with an intermediate probability of bacterial infection. METHODS: In
      this study, 35 COPD outpatients diagnosed by their chest physician with
      moderately severe COPD exacerbation, but without pneumonia, were randomised in a
      double blind, placebo-controlled study. Patients had one or two of the following
      characteristics: a positive Gram's stain of the sputum, 2 or more exacerbations
      in the previous year, a decrease in lung function of >200 mL and >12%. Patients
      received amoxicillin clavulanic acid (500/125 mg three times daily) or placebo
      for 7 days, always combined with a course of prednisolone (30 mg/day) for 7 days.
      Primary outcome was duration of the exacerbation. Additionally, we measured
      severity of the exacerbation, health-related quality of life, sputum parameters,
      number of relapses within 28 days and the number of re-exacerbations within 4
      months after the study. RESULTS: There was no difference observed in time to
      resolution of the exacerbation between the two groups (HR=1.12; (95% CI 0.5 to
      2.3; p=0.77)), nor in any other treatment parameter. CONCLUSIONS: We detected no
      evidence for the effectiveness of addition of antibiotics to prednisolone for
      COPD exacerbations of moderate severity and with intermediate probability of
      bacterial infection in this underpowered study. More placebo-controlled studies
      are needed to properly define subgroups of COPD outpatients in which antibiotics
      are of additional value. TRIALS REGISTRATION NUMBER: clinical trial registered
      with http://www.trialregister.nl/(NTR351).

PMID- 25562036
TI  - Prenatal and Perinatal Morbidity in Children with Tic Disorders: A Mainstream
      School-based Population Study in Central Spain.
AB  - BACKGROUND: While current research suggests that genetic factors confer the
      greatest risk for the development of tic disorders, studies of environmental
      factors are relatively few, with a lack of consistent risk factors across
      studies. Our aim is to analyze the association of tic disorders with exposure to
      prenatal and perinatal morbidity. METHODS: This was a nested case-control study
      design. Cases and controls were selected and identified from a mainstream, school
      based sample. The diagnosis of tic disorders was assigned by a movement disorder
      neurologist using 'Diagnostic and statistical manual of mental disorders, 4th
      edition, text revision' criteria, and neuropsychiatric comorbidities were
      screened using the Spanish computerized version of the Diagnostic Interview
      Schedule for Children Predictive Scale. Information regarding the exposure to pre
      perinatal risk factors was collected by a retrospective review of the birth
      certificates. Logistic regression analyses were then performed to test the
      association of tic disorders with pre-perinatal risk factors. RESULTS: Out of 407
      participants, complete pre-perinatal data were available in 153 children (64 with
      tics and 89 without tics). After adjusting for family history of tics, neonatal
      respiratory distress syndrome, body mass index, prenatal infection, and
      coexisting comorbid neuropsychiatric disturbances, tic disorders were associated
      with prenatal exposure to tobacco (odds ratio [OR] = 3.07, 95% confidence
      interval [CI] 1.24-7.60, p = 0.007), and cesarean section (OR = 5.78, 95% CI 1.60
      20.91, p = 0.01). DISCUSSION: This nested case-control study of children with tic
      disorders demonstrates higher adjusted odds for tics in children with exposure to
      cesarean delivery and maternal smoking. Longitudinal, population-based samples
      are required to confirm these results.

PMID- 25562038
TI  - Out of Africa, into global health security agenda.

PMID- 25562037
TI  - Comparable Botulinum Toxin Outcomes between Primary and Secondary Blepharospasm:
      A Retrospective Analysis.
AB  - BACKGROUND: Blepharospasm is a focal cranial dystonia, which could be idiopathic
      in origin or secondary to an underlying disorder that commonly impairs quality of
      life. Botulinum toxin (BoNT) injections have become the treatment of choice;
      however, a less favorable response to BoNT is expected in secondary
      blepharospasm. No studies have been conducted comparing outcomes between
      blepharospasm cohorts. We therefore aim to compare BoNT outcomes in primary and
      secondary blepharospasm subjects. METHODS: A retrospective review of 64
      blepharospasm subjects receiving BoNT therapy was conducted. Demographics, BoNT
      treatment schedules, duration of BoNT therapy, and side effects were recorded.
      Outcome measures were duration of benefit, peak-dose benefit recorded with the
      Clinical Global Impressions Scale (CGIS), and related side effects. RESULTS: No
      difference was found between the two cohorts regarding duration of benefit from
      treatment (primary 9.47 weeks vs. secondary 9.63 weeks, p = 0.88). Perceived peak
      dose benefit was more commonly reported as "very much improved" in secondary
      patients, but this was not significant (p = 0.13). Higher BoNT dosages were
      required in both groups over time, with a mean increase of 20.5% in primary and
      26.5% in secondary blepharospasm. Ptosis (8%) and diplopia (6%) were the most
      common reported side effects. Mean follow-up in years was similar between groups,
      3.6 years for primary vs. 2.4 years for secondary blepharospasm (p = 0.17).
      DISCUSSION: BoNT injections were effective with comparable benefits seen in both
      primary and secondary blepharospasm populations. Clinicians should be aware of
      the similar benefit from BoNT reported in secondary blepharospasm patients. The
      average duration of benefit in this cohort was comparable with previous reports.

PMID- 25562039
TI  - Optimal Implementation of Intervention to Control the Self-harm Epidemic.
AB  - OBJECTIVES: Deliberate self-harm (DSH) of a young person has been a matter of
      growing concern to parents and policymakers. Prevention and early eradication are
      the main interventional techniques among which prevention through reducing peer
      pressure has a major role in reducing the DSH epidemic. Our aim is to develop an
      optimal control strategy for minimizing the DSH epidemic and to assess the
      efficacy of the controls. METHODS: We considered a deterministic compartmental
      model of the DSH epidemic and two interventional techniques as the control
      measures. Pontryagin's Maximum Principle was used to mathematically derive the
      optimal controls. We also simulated the model using the forward-backward sweep
      method. RESULTS: Simulation results showed that the controls needed to be used
      simultaneously to reduce DSH successfully. An optimal control strategy should be
      adopted, depending on implementation costs for the controls. CONCLUSION: The long
      term success of the optimum control depends on the implementation cost. If the
      cost is very high, the control could be used for a short term, even though it
      fails in the long run. The control strategy, most importantly, should be
      implemented as early as possible to attack a comparatively fewer number of
      addicted individuals.

PMID- 25562040
TI  - Predicting 5-Year Survival Status of Patients with Breast Cancer based on
      Supervised Wavelet Method.
AB  - OBJECTIVES: Classification of breast cancer patients into different risk classes
      is very important in clinical applications. It is estimated that the advent of
      high-dimensional gene expression data could improve patient classification. In
      this study, a new method for transforming the high-dimensional gene expression
      data in a low-dimensional space based on wavelet transform (WT) is presented.
      METHODS: The proposed method was applied to three publicly available microarray
      data sets. After dimensionality reduction using supervised wavelet, a predictive
      support vector machine (SVM) model was built upon the reduced dimensional space.
      In addition, the proposed method was compared with the supervised principal
      component analysis (PCA). RESULTS: The performance of supervised wavelet and
      supervised PCA based on selected genes were better than the signature genes
      identified in the other studies. Furthermore, the supervised wavelet method
      generally performed better than the supervised PCA for predicting the 5-year
      survival status of patients with breast cancer based on microarray data. In
      addition, the proposed method had a relatively acceptable performance compared
      with the other studies. CONCLUSION: The results suggest the possibility of
      developing a new tool using wavelets for the dimension reduction of microarray
      data sets in the classification framework.

PMID- 25562041
TI  - Characterization of Plasmid-Mediated AmpC and Carbapenemases among Iranain
      Nosocomial Isolates of Klebsiella pneumoniae Using Phenotyping and Genotyping
      Methods.
AB  - OBJECTIVES: Plasmid-mediated AmpC beta-lactamases (PMABLs) and carbapenemases are
      emerging groups of antimicrobial-resistance determinants. The aims of the study
      were to evaluate the occurrence of PMABLs and carbapenemases in clinical isolates
      of Klebsiella pneumoniae and compare the test performance of various phenotypic
      methods for detection of these enzymes in Iran. METHODS: A total of 100 K.
      pneumoniae isolates were collected from clinical specimens obtained in Valiasr
      Hospital. AmpC production in all isolates was determined using the AmpC disk
      test, the cephamycin Hodge test, the AmpC Etest, and the boronic acid combined
      disk test. In addition, carbapenemase production was determined using the
      modified Hodge test, the EDTA disk synergy test, and the boronic acid combined
      disk test. The performances of various phenotypic methods were evaluated by the
      comparison of their results with polymerase chain reaction (PCR) method as the
      gold standard. RESULTS: Of the 100 isolates, 19 (19%) were demonstrated to harbor
      the PMABL-resistance gene by the multiplex PCR method. The PCR result indicated
      the presence of carbapenemase genes in 12 isolates. The performance of various
      phenotypic tests carried out for detection of carbapenemase-producing isolates
      varied widely, ranging in sensitivity from 30% to 100% and in specificity from
      90.8% to 100%. CONCLUSION: This is the first report of MOX-type AmpC beta
      lactamase and bla GES in K. pneumoniae in Iran. A comparison of the phenotypic
      methods showed that a combination of cefoxitin plus boronic acid is optimal for
      detecting plasmid-mediated AmpC enzymes in K. pneumoniae, whereas the
      implementation of molecular methods is often complex, requires specially trained
      personnel, and is associated with higher costs.

PMID- 25562042
TI  - Dentofacial and cranial changes in down syndrome.
AB  - OBJECTIVES: This study aimed to determine the prevalence of certain oral
      characteristics usually associated with Down syndrome and to determine the oral
      health status of these patients. METHODS: The cross-sectional study was conducted
      among patients attending a special education program at Faculty of Dentistry,
      Jamia Millia Islamia, Delhi, India. The study design consisted of closed-ended
      questions on demographic characteristics (age, sex, and education and income of
      parents), dietary habits, and oral hygiene habits. Clinical examination included
      assessment of oral hygiene according to Simplified Oral Hygiene Index (OHI-S),
      dental caries according to decayed, missing, and filled teeth (DMFT) index,
      periodontal status according to the Community Periodontal Index of Treatment
      Needs (CPITN), and malocclusion according to Angles classification of
      malocclusion. Examinations were carried out using a using a CPI probe and a mouth
      mirror in accordance with World Health Organization criteria and methods.
      Craniometric measurements, including maximum head length and head breadth were
      measured for each participant using Martin spreading calipers centered on
      standard anthropological methods. RESULTS: The majority of the patients were
      males (n = 63; 82%) with age ranging from 6-40 years. The Intelligence Quotient
      (IQ) score of the patients indicated that 31% had moderate mental disability and
      52% had mild mental disability. 22% exhibited hearing and speech problems.12% had
      missing teeth and 15% had retained deciduous teeth in adult population. The
      overall prevalence of dental caries in the study population was 78%. DMFT, CPITN
      and OHI scores of the study group were 3.8 +/- 2.52, 2.10 +/- 1.14 and 1.92 +/-
      0.63 respectively. The vast majority of patients required treatment (90%),
      primarily of scaling, root planing, and oral hygiene education. 16% of patients
      reported CPITN scores of 4 (deep pockets) requiring complex periodontal care. The
      prevalence of malocclusion was 97% predominantly of Class III malocclusions.
      Further 14% presented with fractured anterior teeth primarily central incisor.
      The percentage means of cephalic index was 84.6% in the study population. The
      brachycephalic and hyperbrachycephalic type of head shape was dominant in the
      Down syndrome individuals (90%). CONCLUSION: The most common dentofacial anomaly
      seen in these individuals was fissured tongue followed by macroglossia.

PMID- 25562043
TI  - Aging-related Changes in Mouse Serum Glycerophospholipid Profiles.
AB  - OBJECTIVES: Metabolic dysfunction is a common hallmark of the aging process and
      aging-related pathogenesis. Blood metabolites have been used as biomarkers for
      many diseases, including cancers, complex chronic diseases, and neurodegenerative
      diseases. METHODS: In order to identify aging-related biomarkers from blood
      metabolites, we investigated the specific metabolite profiles of mouse sera from
      4-month-old and 21-month-old mice by using a combined flow injection analysis
      tandem mass spectrometry and liquid chromatography-tandem mass spectrometry.
      RESULTS: Among the 156 metabolites detected, serum levels of nine individual
      metabolites were found to vary with aging. Specifically, lysophosphatidylcholine
      (LPC) acyl (a) C24:0 levels in aged mice were decreased compared to that in young
      mice, whereas phosphatidylcholine (PC) acyl-alkyl (ae) C38:4, PC ae C40:4, and PC
      ae C42:1 levels were increased. Three classes of metabolites (amino acids, LPCs,
      and PCs) differed in intraclass correlation patterns of the individual
      metabolites between sera from young and aged mice. Additionally, the ratio of LPC
      a C24:0 to PC ae C38:4 was decreased in the aged mice, whereas the ratio of PC ae
      C40:4 to LPC a C24:0 was increased, supporting the aging-related metabolic
      changes of glycerophospholipids. CONCLUSION: The ratios of the individual
      metabolites PC and LPC could serve as potential biomarkers for aging and aging
      related diseases.

PMID- 25562044
TI  - Rapid DNA extraction from dried blood spots on filter paper: potential
      applications in biobanking.
AB  - OBJECTIVES: Dried blood spot (DBS) technology is a microsampling alternative to
      traditional plasma or serum sampling for pharmaco- or toxicokinetic evaluation.
      DBS technology has been applied to diagnostic screening in drug discovery,
      nonclinical, and clinical settings. We have developed an improved elution
      protocol involving boiling of blood spots dried on Whatman filter paper. METHODS:
      The purpose of this study was to compare the quality, purity, and quantity of DNA
      isolated from frozen blood samples and DBSs. We optimized a method for extraction
      and estimation of DNA from blood spots dried on filter paper (3-mm FTA card). A
      single DBS containing 40 MUL blood was used. RESULTS: DNA was efficiently
      extracted in phosphate-buffered saline (PBS) or Tris-EDTA (TE) buffer by
      incubation at 37 degrees C overnight. DNA was stable in DBSs that were stored at
      room temperature or frozen. The housekeeping genes GAPDH and beta-actin were used
      as positive standards for polymerase chain reaction (PCR) validation of general
      diagnostic screening. CONCLUSION: Our simple and convenient DBS storage and
      extraction methods are suitable for diagnostic screening by using very small
      volumes of blood collected on filter paper, and can be used in biobanks for blood
      sample storage.

PMID- 25562045
TI  - Antihematotoxic Role of Bunium persicum Seed Differential Extracts in Animal
      Model: Reactive Oxygen Species Might Be a Contributor.
AB  - OBJECTIVES: Humans have been using plants as natural medicines since prehistoric
      times. Bunium persicum is a rich source of oils with different biological
      activities such as antioxidative and antimicrobial activities. The aim of this
      study is to evaluate the antihematotoxic and antioxidative effects of the
      differential extracts of B. persicum against leukemic blood induced
      hematotoxicity in an animal model. METHODS: This study was performed on animals,
      which were divided into several groups: normal control, disease control, and
      groups that were administered with differential extracts of plants. We measured
      the concentration of free radical [reactive oxygen species (ROS)] and
      hematological parameters as blast cells from the tibia and femur in different
      groups. RESULTS: The ROS level and blast cells count were higher in disease
      control groups than in groups treated with varying amounts of B. persicum extract
      and the normal group. Moreover, there was an imbalance in hematological
      parameters in untreated and treated groups with a correlation between free
      radicals and plant extract administration. CONCLUSION: These findings may
      indicate a possible link between free radicals and hematotoxicity and blast
      cells, while depicting a potential therapeutic role for B. persicum against ROS
      induced hematotoxicity.

PMID- 25562046
TI  - Diversity of rotavirus strain circulated in gwangju, republic of Korea.
AB  - OBJECTIVES: The introduction of new rotavirus vaccines into the public sphere
      makes it necessary to maintain constant surveillance and to heighten public
      awareness of the appearance of new rotavirus strains. We describe the molecular
      epidemiology of circulating rotavirus strains after vaccine introduction.
      METHODS: We collected a total of 1070 stool samples from children with
      gastroenteritis from January 2013 to June 2013. The antigenic prevalence of
      rotavirus group A was distinguished using enzyme immunoassay. The G and P
      genotypes of enzyme immunoassay-positive samples were determined with reverse
      transcription-polymerase chain reaction and nucleotide sequencing analysis.
      RESULTS: Of the 1070 samples collected, 277 (25.9%) tested positive for
      rotaviruses by enzyme-linked immunoabsorbent assay. The most prevalent
      circulating genotype G was G1 (51.3%), followed by G2 (34.7%) and G9 (10.8%). The
      predominant type of genotype P was P[8] (66.1%), followed by P[4] (31.4%). In
      this study, nine genotypes were found. G1P[8] was the most prevalent (51.8%),
      followed by G2P[4] (30.5%), G9P[8] (9.9%), and G2P[8] (4.0%). Several unusual
      combinations (G1P[4], G3P[9], G3P[8], G4P[6], and G9P[4]) were also identified.
      CONCLUSION: Molecular epidemiological knowledge of rotaviruses is critical for
      the development of effective preventive measures, including vaccines. These data
      will help us monitor the effectiveness of current rotavirus vaccines.

PMID- 25562047
TI  - Composition of metabolic syndrome among korean adults in a lifestyle modification
      intervention.
AB  - OBJECTIVES: The aim of this study was to examine the composition of metabolic
      syndrome (MetS) components among middle-aged and older Koreans. METHODS: A total
      of 263 participants (age 40 + years) in a lifestyle modification intervention
      program who met the MetS definition of National Cholesterol Education Program
      (NCEP) - Adult Treatment Panel (ATP) III criteria were included in the study. The
      frequent patterns and clustering of MetS components were investigated. Clustering
      of changes in individual components, through a lifestyle modification
      intervention, was also identified. All characteristics were stratified by and
      compared between sexes. RESULTS: Approximately 80% of the participants had three
      of five MetS risk factors at baseline. The prevalence of each risk differed by
      sex. MetS composition patterns that do not include low high-density lipoprotein
      (HDL) cholesterol were more noticeable in men because of the low prevalence of
      low HDL cholesterol. In women, with higher prevalence of low HDL cholesterol,
      more patterns that include low HDL cholesterol were observed. The most common
      combination was "elevated blood pressure + abdominal obesity + impaired fasting
      glucose" in both sexes. Clustering of MetS risks was also found with most of the
      frequent combinations of MetS components. Through the lifestyle intervention, the
      greatest change was observed in HDL cholesterol among men and blood pressure
      among women. Triglycerides and HDL cholesterol were likely to be improved with
      blood pressure in men and abdominal obesity in women. CONCLUSION: Differences in
      the prevalent patterns of MetS compositions were observed prior to and after the
      intervention, along with during-intervention changes. It is recommended that
      intervention strategies and guidelines for MetS management consider the MetS
      composition patterns for effectiveness.

PMID- 25562048
TI  - Ebola hemorrhagic Fever and the current state of vaccine development.
AB  - Current Ebola virus outbreak in West Africa already reached the total number of
      1,323 including 729 deaths by July 31st. the fatality is around 55% in the
      southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of
      patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even
      though the any effective therapeutics or vaccines has not been developed yet. The
      Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the
      pathogenesis of Ebola virus infection and assess of the various candidates of
      vaccine have been tried for a long time, especially in United States and some
      European countries. Even though the attenuated live vaccine and DNA vaccine
      containing Ebola viral genes were tested and showed efficacy in chimpanzees,
      those candidates still need clinical tests requiring much longer time than the
      preclinical development to be approved for the practical treatment. It can be
      expected to eradicate Ebola virus by a safe and efficient vaccine development
      similar to the case of smallpox virus which was extinguished from the world by
      the variola vaccine. 

PMID- 25562049
TI  - Acute human cytomegalovirus infection with bleeding in iran.
AB  - In December 2011, a 42-year-old male farmer was admitted to a hospital in
      Sanandaj (Western Iran) with fever and anemia in order to check whether he
      suffered from some infectious diseases. During the first 3 days after admission,
      the patient gradually developed progressive oliguria, fever, abdominal pain in
      the right upper quadrant, leukocytosis with toxic granulation, petechiae and
      ecchymosis, oral bleeding, and vomiting. The sonographic findings revealed
      splenomegaly and an increase in the thickness of the gall bladder wall. In order
      to manage the patient and taking into consideration the most probable
      differential diagnoses, diagnostic tests were performed on two blood samples
      collected from him, and real-time polymerase chain reaction for human
      cytomegalovirus was positive. 

PMID- 25562051
TI  - Brain treatments and creativity.

PMID- 25562052
TI  - January 1920: the beginning of nationwide sobriety.

PMID- 25562053
TI  - Marijuana use in athletics.

PMID- 25562054
TI  - Public-private partnerships, programs target infectious diseases in RI.

PMID- 25562055
TI  - Tuberculosis control in RI: maintaining control efforts in the context of
      declining incidence and funding for tuberculosis programs.

PMID- 25562056
TI  - Tuberculous meningitis in child born in the US to immigrants from a tuberculosis
      endemic country.
AB  - This is a case of a child born in the US to immigrant parents from a tuberculosis
      (TB)-endemic area of Liberia who was diagnosed with TB meningitis after a greater
      than 1-month history of unremitting fever. This report aims to highlight the
      importance of early identification of TB in the pediatric population with risk
      factors for TB and considering TB as a diagnosis among US born children to
      immigrants from TB-endemic countries.

PMID- 25562050
TI  - Stress, social behavior, and resilience: insights from rodents.
AB  - The neurobiology of stress and the neurobiology of social behavior are deeply
      intertwined. The social environment interacts with stress on almost every front:
      social interactions can be potent stressors; they can buffer the response to an
      external stressor; and social behavior often changes in response to stressful
      life experience. This review explores mechanistic and behavioral links between
      stress, anxiety, resilience, and social behavior in rodents, with particular
      attention to different social contexts. We consider variation between several
      different rodent species and make connections to research on humans and non-human
      primates.

PMID- 25562057
TI  - Monitored viral load: a measure of HIV treatment outcomes in an outpatient
      setting in Rhode Island.
AB  - Community viral load measurements have been postulated to be a population-based
      biomarker of HIV disease. We propose the use of the monitored community viral
      load (mCVL) as an aggregate measure of viral load among persons receiving HIV
      care with available HIV-1 plasma viral loads and applied it to our clinic
      population from 2003-2010. We demonstrated a reduction in mCVL from 16,589
      copies/ml to 11,992 copies/ml that correlated with a rising rate of
      antiretroviral use and HIV viral suppression; however, differences among risk
      populations were observed. The mCVL is a useful measure of HIV burden among
      patients in-care; it may reflect the HIV transmission risk in the community and
      help target preventive interventions.

PMID- 25562058
TI  - Addressing the increasing burden of sexually transmitted infections in Rhode
      Island.
AB  - The rates of sexually transmitted infections (STI) including chlamydia,
      gonorrhea, and syphilis, are increasing across the United States, including in
      Rhode Island (RI). These STIs affect many otherwise healthy adolescents and young
      adults, and represent a significant source of morbidity. The Centers for Disease
      Control and Prevention encourages states to develop strategies for addressing
      increasing STI rates in the setting of diminishing public health resources. The
      RI Department of Health (DOH) works with providers and funded community- based
      organizations to promote STI screening, expedited partner therapy, and partner
      services to reduce STI rates. The Miriam Hospital Immunology Center opened a
      public HIV/STI Clinic, which offers free and confidential testing for HIV, viral
      hepatitis, chlamydia, gonorrhea, and syphilis, as well as post-exposure
      prophylaxis (PEP) and pre-exposure prophylaxis (PrEP) services to prevent HIV. In
      collaboration with the RI DOH, the Clinic serves as a referral source across the
      state for complicated STI cases.

PMID- 25562059
TI  - Tick-borne illness in Rhode Island - how big a problem is it?
AB  - Rhode Island is a state with a high incidence of tick-borne diseases,
      specifically Lyme disease. The Ioxedes tick which serves as vector for the three
      most common tick infections is endemic in both the New England and mid-Atlantic
      regions. However, differences in the density of infections exist within Rhode
      Island (RI), with the highest densities in the southern counties. Tick-borne
      diseases can have varying presentations, as well as varied response to
      appropriate treatment leading to many questions and confusion for patients,
      clinicians, and the public itself.

PMID- 25562060
TI  - Outpatient parenteral antibiotic therapy in an academic practice in Rhode Island.
AB  - Outpatient parenteral antimicrobial therapy (OPAT) is an increasingly utilized
      treatment modality that has been proven to be safe and cost effective for
      treating infections that require prolonged antimicrobial treatment. Adequate
      patient selection, a structured OPAT team with an effective communication system,
      and routine clinical monitoring are key elements to establish a successful OPAT
      program. The Miriam Hospital Infectious Diseases Clinic offers a
      multidisciplinary OPAT model coordinated by infectious diseases specialists and
      serves as a major referral center in Rhode Island.

PMID- 25562061
TI  - Pediatric refugees in Rhode Island: increases in BMI percentile, overweight, and
      obesity following resettlement.
AB  - OBJECTIVE: To evaluate BMI change among pediatric refugees resettling in
      Providence, RI. METHODS: Retrospective chart review of pediatric refugees from
      the initial evaluation to year 3 post-resettlement at Hasbro Children's Hospital.
      Primary outcome of interest was within person change in BMI percentile at each
      time point. RESULTS: From 2007-2012, 181 children visited the clinic. Initial
      prevalence of overweight and obesity was 14.1% and 3.2% versus 22.8% and 12.6% at
      year 3. From visit 1 and years 1-3, there was a positive mean within person
      change in BMI percentile of 12.9% (95% CI 6.3-19.6%s), 16.6% (95% CI 11.2-21.9%),
      and 14.4% (95% CI 9.1-19.7%). CONCLUSIONS: The prevalence of overweight and
      obesity increased from 17.3% at initial intake to 35.4% at 3 years post
      resettlement to surpass that of American children (31.7-31.8% for 2007-2012).
      Refugee children have additional risk factors for obesity; multidisciplinary
      interventions must be designed to address nutrition at each visit.

PMID- 25562062
TI  - Treating children at Urgent Care Centers: a qualitative study to determine how
      providers perceive managing pediatric patients.
AB  - As Urgent Care Centers (UCCs) multiply, more children receive care in this
      setting. Little is known about UCC providers' perspectives on the management of
      common pediatric conditions. The objectives of this study are to describe the
      perceptions of UCC providers and identify challenges they face regarding common
      pediatric conditions. This qualitative study used semi-structured interviews with
      a convenience sample of 12 UCC providers from 9 non-academic UCCs in Rhode
      Island. Content analysis identified themes that describe perceptions of UCC
      providers regarding pediatric patients. Interviews identified three common
      pediatric scenarios that challenged UCC providers: acutely ill young infants,
      minor traumatic brain injury (mTBI), and uncooperative children requiring minor
      procedures. UCCs should focus quality initiatives to educate their providers on
      evidence-based management of common pediatric clinical scenarios. Efforts may
      include dissemination of validated guidelines, education targeted to non
      pediatric trained providers, and the integration of minimal sedation protocols
      for minor procedures.

PMID- 25562063
TI  - A broken heart: a woman with chest pain and an abnormal ECG.

PMID- 25562064
TI  - Transmission versus transflection mode in FTIR analysis of blood plasma: is the
      electric field standing wave effect the only reason for observed spectral
      distortions?
AB  - Fourier transform infrared (FTIR) microspectroscopy is assessed in terms of two
      techniques (i.e., transmission and transflection) as a method for rapid
      measurements of blood plasma. Apart from the expected effect of the electric
      field standing wave (EFSW), we also noticed that second-derivative IR spectra
      recorded in transflection mode exhibited a significant shift in the amide I band
      (up to 1667 cm(-1)) in comparison to the one recorded in transmission (1658 cm(
      1)). This has not been reported thus far in studies of the EFSW distortion of IR
      spectra of biological material. The thinner the sample deposited on the low-e
      microscope slide, the lower the position of the amide I band found in FTIR
      spectra, suggesting various plasma compositions after stratification or certain
      changes in secondary protein conformations due to chemical and/or physical
      effects. There are potentially several phenomena that can occur at the surface of
      both IR substrates affecting the protein profile, including changes in optical
      properties (refractive index), variation in water content in the sample, and
      segregation of plasma components. All three hypotheses are discussed here, with
      the help of atomic force microscopy (AFM). 

PMID- 25562065
TI  - Screening and mapping of pigments in paintings using scanning electrochemical
      microscopy (SECM).
AB  - The use of the scanning electrochemical microscopy (SECM) technique for
      identifying and mapping of both organic and inorganic pigments in sub
      microsamples from pictorial specimens is described. This methodology, inspired by
      the voltammetry of immobilized particles technique, permits the study of textural
      properties of paint layers and mapping the distribution of pigment grains upon
      application of different potentials to the substrate. A combination of the redox
      competition SECM strategy with voltammetry yields a local identification
      methodology for different organic and inorganic pigments in paint samples. 

PMID- 25562066
TI  - An enzyme-free and amplified colorimetric detection strategy: assembly of gold
      nanoparticles through target-catalytic circuits.
AB  - Herein we introduce an enzyme-free and amplified colorimetric detection strategy,
      which is based on gold nanoparticle (AuNP) aggregation through target-catalytic
      DNA circuits (HCR and CHA). 

PMID- 25562067
TI  - Rational design of sulphur host materials for Li-S batteries: correlating lithium
      polysulphide adsorptivity and self-discharge capacity loss.
AB  - A versatile, cost-effective electrochemical analysis strategy is described that
      determines the specific S(n)(2-) adsorptivity of materials, and allows prediction
      of the long-term performance of sulphur composite electrodes in Li-S cells.
      Measurement of nine different materials with varying surface area, and
      hydrophobicity using this protocol determined optimum properties for capacity
      stabilization.

PMID- 25562068
TI  - Thermodynamic insights into the self-assembly of capped nanoparticles using
      molecular dynamic simulations.
AB  - Although the molecular modeling of self-assembling processes stands as a
      challenging research issue, there have been a number of breakthroughs in recent
      years. This report describes the use of large-scale molecular dynamics
      simulations with coarse grained models to study the spontaneous self-assembling
      of capped nanoparticles in chloroform suspension. A model system comprising 125
      nanoparticles in chloroform evolved spontaneously from a regular array of
      independent nanoparticles to a single thread-like, ramified superstructure
      spanning the whole simulation box. The aggregation process proceeded by means of
      two complementary mechanisms, the first characterized by reactive collisions
      between monomers and oligomers, which were permanently trapped into the growing
      superstructure, and the second a slow structural reorganization of the
      nanoparticle packing. Altogether, these aggregation processes were over after ca.
      0.6 MUs and the system remained structurally and energetically stable until 1
      MUs. The thread-like structure closely resembles the TEM images of capped ZrO2,
      but a better comparison with experimental results was obtained by the deposition
      of the suspension over a graphene solid substrate, followed by the complete
      solvent evaporation. The agreement between the main structural features from this
      simulation and those from the TEM experiment was excellent and validated the
      model system. In order to shed further light on the origins of the stable
      aggregation of the nanoparticles, the Gibbs energy of aggregation was computed,
      along with its enthalpy and entropy contributions, both in chloroform and in a
      vacuum. The thermodynamic parameters arising from the modeling are consistent
      with larger nanoparticles in chloroform due to the solvent-swelled organic layer
      and the overall effect of the solvent was the partial destabilization of the
      aggregated state as compared to the vacuum system. The modeling strategy has been
      proved effective and reliable to describe the self-assembling of capped
      nanoparticles, but we must acknowledge the fact that larger model systems and
      longer timescales will be necessary in future investigations in order to assess
      structural and dynamical information approaching the behavior of macroscopic
      systems. 

PMID- 25562069
TI  - Kinetics of stabilised Criegee intermediates derived from alkene ozonolysis:
      reactions with SO2, H2O and decomposition under boundary layer conditions.
AB  - The removal of SO2 in the presence of alkene-ozone systems has been studied for
      ethene, cis-but-2-ene, trans-but-2-ene and 2,3-dimethyl-but-2-ene, as a function
      of humidity, under atmospheric boundary layer conditions. The SO2 removal
      displays a clear dependence on relative humidity for all four alkene-ozone
      systems confirming a significant reaction for stabilised Criegee intermediates
      (SCI) with H2O. The observed SO2 removal kinetics are consistent with relative
      rate constants, k(SCI + H2O)/k(SCI + SO2), of 3.3 (+/-1.1) * 10(-5) for CH2OO, 26
      (+/-10) * 10(-5) for CH3CHOO derived from cis-but-2-ene, 33 (+/-10) * 10(-5) for
      CH3CHOO derived from trans-but-2-ene, and 8.7 (+/-2.5) * 10(-5) for (CH3)2COO
      derived from 2,3-dimethyl-but-2-ene. The relative rate constants for k(SCI
      decomposition)/k(SCI + SO2) are -2.3 (+/-3.5) * 10(11) cm(-3) for CH2OO, 13 (+/
      43) * 10(11) cm(-3) for CH3CHOO derived from cis-but-2-ene, -14 (+/-31) * 10(11)
      cm(-3) for CH3CHOO derived from trans-but-2-ene and 63 (+/-14) * 10(11) cm(-3)
      for (CH3)2COO. Uncertainties are +/-2sigma and represent combined systematic and
      precision components. These values are derived following the approximation that a
      single SCI is present for each system; a more comprehensive interpretation,
      explicitly considering the differing reactivity for syn- and anti-SCI conformers,
      is also presented. This yields values of 3.5 (+/-3.1) * 10(-4) for k(SCI +
      H2O)/k(SCI + SO2) of anti-CH3CHOO and 1.2 (+/-1.1) * 10(13) for k(SCI
      decomposition)/k(SCI + SO2) of syn-CH3CHOO. The reaction of the water dimer with
      CH2OO is also considered, with a derived value for k(CH2OO + (H2O)2)/k(CH2OO +
      SO2) of 1.4 (+/-1.8) * 10(-2). The observed SO2 removal rate constants, which
      technically represent upper limits, are consistent with decomposition being a
      significant, structure dependent, sink in the atmosphere for syn-SCI. 

PMID- 25562070
TI  - Anodization control for barrier-oxide thinning and 3D interconnected pores and
      direct electrodeposition of nanowire networks on native aluminium substrates.
AB  - Here we report a strategy for combining techniques for pore branching and barrier
      layer thinning to produce 3D porous anodized aluminum oxide films with direct
      ohmic contact to the native aluminum. This method provides an example of a
      rationally designed template which need not be removed from the aluminum, but
      which is also not constrained to traditional 2D pore geometry. We first
      demonstrate the barrier layer removal and pore branching techniques
      independently, and then combine them to produce free standing arrays of
      interconnected Ni nanostructures. Nickel nanostructures are deposited directly
      onto the aluminum to demonstrate the success of the structural modification, and
      showcase the potential for these films to be used as templates. This approach is
      the first to demonstrate the design and execution of multiple pore modification
      techniques in the same membrane, and demonstrates the first directly deposited 3D
      structures on aluminum substrates. 

PMID- 25562071
TI  - Magnetic gamma-Fe2O3, Fe3O4, and Fe nanoparticles confined within ordered
      mesoporous carbons as efficient microwave absorbers.
AB  - A series of magnetic gamma-Fe2O3, Fe3O4, and Fe nanoparticles have been
      successfully introduced into the mesochannels of ordered mesoporous carbons by
      the combination of the impregnation of iron salt precursors and then in situ
      hydrolysis, pyrolysis and reduction processes. The magnetic nanoparticles are
      uniformly dispersed and confined within the mesopores of mesoporous carbons.
      Although the as-prepared magnetic mesoporous carbon composites have high contents
      of magnetic components, they still possess very high specific surface areas and
      pore volumes. The magnetic hysteresis loops measurements indicate that the
      magnetic constituents are poorly-crystalline nanoparticles and their saturation
      magnetization is evidently smaller than bulky magnetic materials. The confinement
      of magnetic nanoparticles within the mesopores of mesoporous carbons results in
      the decrease of the complex permittivity and the increase of the complex
      permeability of the magnetic nanocomposites. The maximum reflection loss (RL)
      values of -32 dB at 11.3 GHz and a broad absorption band (over 2 GHz) with RL
      values <-10 dB are obtained for 10-Fe3O4-CMK-3 and 10-gamma-Fe2O3-CMK-3
      composites in a frequency range of 8.2-12.4 GHz (X-band), showing their great
      potentials in microwave absorption. This research opens a new method and idea for
      developing novel magnetic mesoporous carbon composites as high-performance
      microwave absorbing materials. 

PMID- 25562072
TI  - Stabilities and electronic properties of monolayer MoS2 with one or two sulfur
      line vacancy defects.
AB  - Stimulated by the recent experimental observation that single sulfur vacancies in
      monolayer MoS2 are mobile under the electron beam and easily agglomerate into the
      sulfur line vacancy defects [Phys. Rev. B: Condens. Matter Mater. Phys., 2013,
      88, 035301], the stabilities and electronic properties of monolayer MoS2 with one
      or two staggered sulfur line vacancy defects (SV or DV), along the armchair or
      zigzag direction (AC-SV, AC-DV or ZZ-SV, ZZ-DV), have been investigated
      systematically by first-principles calculations. It is found that: (1) The ZZ
      types (ZZ-SV and ZZ-DV) are more stable at different line vacancy densities than
      the AC-types (AC-SV and AC-DV), which is in good agreement with previous
      experimental findings. (2) More interestingly, it is predicted from our numerical
      calculations that, in the same ZZ-types, the ZZ-DV is more stable than the ZZ-SV,
      indicating that two separate ZZ-SV line vacancy defects tend to move closely to
      each other for coalescing into a ZZ-DV, which is in contrast to the AC-type with
      AC-SV being a little more stable than the AC-DV. (3) The monolayer MoS2 with the
      AC-SV or AC-DV are both semiconductors with a direct or an indirect band gap,
      respectively, both of which are significantly smaller than that of the perfect
      monolayer. (4) Furthermore, the out-of-plane distortion induced by strain release
      in the monolayer MoS2 with ZZ-SV or ZZ-DV is more severe than that with the AC
      type, which can further considerably decrease the system's gap value or even make
      the gap nearly closed. Our calculation results will be helpful in future
      nanoelectronics and nanoelectromechanics based on MoS2 materials. 

PMID- 25562073
TI  - Resonance Raman detection of the myoglobin nitrito heme Fe-O-N=O/2-nitrovinyl
      species: implications for helix E-helix F interactions.
AB  - The description of biological activity in heme proteins responsible for
      activating small molecules requires identification of ligand movement into the
      metal and non-metal binding sites. Mechanisms of nitrite reductase activity in
      globins are difficult to verify without the structures of the bound ligand, but
      we now have such information from resonance Raman spectroscopy on the myoglobin
      nitrito heme Fe-O-N=O/2-nitrovinyl species in their natural environment rather
      than in crystals. Our results indicate that the formation of the nitrito heme Fe
      O-N=O/2-nitrovinyl species is pH-dependent. The conditions under which the
      nitrito heme Fe-O-N=O/2-nitrovinyl species is generated strongly suggest that
      this form corresponds to an acid induced transformation. We propose that the
      movement of helices E and F at low pH results in the protonation of nitrito heme
      Fe-O-N=O by His64 Nepsilon-H(E) to form the nitrous heme Fe-O(H)-N=O species.

PMID- 25562074
TI  - How and why can I sign up?

PMID- 25562075
TI  - Dental implants and a rising demand to immediately improve patients' oral
      function and esthetics: is research conclusive?

PMID- 25562076
TI  - Energy balance and mortality.

PMID- 25562077
TI  - The contraceptive needs of the perimenopausal woman.

PMID- 25562078
TI  - Prevalence of urinary incontinence according to hysterectomy status in the WHI
      observational study.

PMID- 25562079
TI  - Author's response.

PMID- 25562080
TI  - Body image and depression.

PMID- 25562081
TI  - Preventive medicine: GYNs or GPs?

PMID- 25562082
TI  - Epigenetics and periodontal disease: hope to tame the untameable.
AB  - Epigenetics means gene expression alterations which occur due to the biochemical
      changes of the nucleotides modifying structure of DNA rather than the changes in
      the genetic code itself as in case of mutations. The epigenome, consisting of
      chromatin and its modifications, acts as a link between the inherited genome and
      the changes imposed by the environment. Over the past decade, there has been
      mounting evidence suggestive of associations between epigenetic modifications and
      various human conditions such as aging, and most common human diseases viz.
      cancer, cardiovascular diseases, diabetes, rheumatoid arthritis, HIV etc and the
      clearest evidence as the central mechanism for common multifactorial diseases,
      has been identified with the factors involved in the inflammatory response.
      Periodontal disease, basically an immune-inflammatory affliction, being a
      multifactorial complex disease, owing to its high prevalence, chronicity and wide
      ranging systemic effects, essentially calls for a better comprehension of the
      underlying disease mechanisms, so as to develop and decipher the novel
      methodologies to combat this disease. The current paper aims to visualize
      periodontal disease from an epigenetic perspective, featuring the contemporary
      evidence supported literature and tends to explore the possibilities to find some
      explanations for perio-systemic health links, individualized and improvised
      diagnostic tools for earlier detection and ways to halt the disease and help
      regeneration and reconstruction of the lost periodontal attachment apparatus with
      the biology based approaches.

PMID- 25562083
TI  - Commentary on Bellamy G, Gott M and Hinchliff S (2013) Women's understandings of
      sexual problems: findings from an in-depth interview study. Journal of Clinical
      Nursing, 22, 3240-3248.

PMID- 25562084
TI  - Coping, subjective burden and anxiety among family caregivers  of older
      dependents.
AB  - AIMS AND OBJECTIVES: To investigate relationships between anxiety and
      stressors,coping and subjective burden and to contribute to defining factors
      related to anxiety among family caregivers of older dependents. BACKGROUND:
      Despite the studies analysing factors related to anxiety in caregivers, there is
      not enough evidence about this issue. DESIGN: Cross-sectional design. METHODS:
      Data from 140 family caregivers (convenience sample) were analysed using
      descriptive statistics, correlation coefficients and path analysis. Socio
      demographic data and several scales (Barthel Index, Short Portable Mental Status
      Questionnaire, Cummings Neuropsychiatric Inventory, Brief COPE, Caregiver Strain
      Index and Hamilton Anxiety Rating Scale) were used to collect data. RESULTS:
      Stressors (psychiatric and psychological symptoms and number of assisted
      activities of daily living), emotion-focused coping, dysfunctional coping and
      subjective burden were related to greater anxiety. Subjective burden mediated the
      effects of psychiatric and psychological symptoms on anxiety and partially
      mediated the effects of dysfunctional coping on anxiety. CONCLUSIONS: Stressors,
      dysfunctional coping and subjective burden were identified as factors related to
      anxiety. The mediating role of subjective burden in the relationship between
      dysfunctional coping and anxiety was supported. The effect of dysfunctional
      coping on anxiety was independent of the stressors. RELEVANCE TO CLINICAL
      PRACTICE: These conclusions justify several recommendations regarding nursing
      interventions for family caregivers of older dependents: (1)
      stressors,dysfunctional coping and subjective burden can be used in clinical
      practice for early detection of and early intervention for anxiety; (2) to
      prevent subjective burden and anxiety,approach-coping skills should be promoted
      through interventions such as problem-solving,positive reappraisal, assertiveness
      and control of negative thoughts; (3) these interventions for dysfunctional
      coping should be systematically developed for individuals with dysfunctional
      coping regardless of the level of stressors and/or the possibility of respite.

PMID- 25562086
TI  - Author response.

PMID- 25562087
TI  - Author response.

PMID- 25562085
TI  - Symposium in honor of Ferdinando Rossi: a passionate journey through the
      cerebellar mysteries.
AB  - To remember our friend and colleague Ferdinando Rossi, prematurely passed away on
      24th January 2014, a symposium was held during the ninth FENS meeting in Milan.
      It was focused on the development and plasticity of the cerebellum, the main
      topics of Ferdinando's research. From the talks of the invited speakers, Giacomo
      Consalez, Karl Schilling, Alain Chedotal, and Chris De Zeeuw, it clearly emerged
      that Ferdinando had a huge impact on the research of many scientists like them,
      as well as in the whole field of brain development and regeneration. With this
      symposium, we celebrated a brilliant scientist, devoted to Neuroscience with
      tireless passion and curiosity.

PMID- 25562088
TI  - [Injuries of the upper extremities (shoulder girdle, shoulder joint)].

PMID- 25562089
TI  - Preface. Chromosomal mutagenesis.

PMID- 25562090
TI  - Preface. Plant cell expansion.

PMID- 25562091
TI  - Treatment of thoracic spine hyperextension injury.

PMID- 25562092
TI  - Adolescent idiopathic scoliosis surgery with patient-specific screw placement
      guides.

PMID- 25562093
TI  - Percutaneous, cement-augmented reposition and stabilisation of burst fractures T9
      and T12 in osteoporosis.

PMID- 25562095
TI  - [Not Available].

PMID- 25562094
TI  - In-situ L5-S1 fusion of a stable, sagittally balanced L5 spondyloptosis.

PMID- 25562096
TI  - [50 years history of Czecho-slovak pathology journal].

PMID- 25562098
TI  - [Not Available].

PMID- 25562099
TI  - [Not Available].

PMID- 25562097
TI  - Influence of media on suicide: proper coverage of media on suicide report: the
      authors response.

PMID- 25562100
TI  - Sleep quality, use of hypnotics and sleeping habits in  different age-groups
      among older people.
AB  - BACKGROUND: Sleep disturbances are common among older people (>65 years).
      Further, long-term use of sedative hypnoticsin older people is associated with
      morbidity and mortality. However, older people represent a large span of life
      years, and few studies have included the oldest-old above 85 years. AIM: To
      investigate and compare sleep quality, use of hypnotics and sleeping habits in
      different age groups of the older population in the Scania region, Sweden and in
      relation to sociodemographic- and functional status. DESIGN AND PARTICIPANTS: A
      cross-sectional population-based study including 2931 people aged 60-93 years
      from five different municipalities in Scania was performed during 2001-2004.
      METHOD: The sample was divided into age groups, young old (60-72 years), old-old
      (78-84 years) and oldest-old (87-93) years. Data constitutes of sleep related
      questions, sociodemographic- and functional status from the study 'Good Ageing in
      Skane'. Descriptive statistics were used to describe sleep quality, hypnotics use
      and sleeping habitsin relation to sociodemographic- and functional status. The
      aim was to investigate associations, not the magnitude of associations between
      variables. RESULTS: In all age groups, those who used hypnotics and were living
      alone had significantly poorer sleep quality and shortest sleeping time than
      nonhypnotic users and those who lived together. A significant increase of
      hypnotics and frequency of use was seen with increasing age. Frequency of napping
      increased significantly with degree of dependence in all age groups and with
      increasing age. CONCLUSIONS: Insomnia is still a problem and hypnotic use has not
      improved sleep for a large number of older people. Hypnotics are effective as
      short-term treatment, however, nonpharmacological interventions and psychological
      and behavioural therapies should be considered for treating older people with
      chronic insomnia.

PMID- 25562102
TI  - Sex: where morals and medicine collide.

PMID- 25562101
TI  - Reply to Victora et al.

PMID- 25562103
TI  - EBV-positive peripheral T-cell lymphoma with  extensive hemophagocytosis.

PMID- 25562104
TI  - Author's reply: To PMID 22582741.

PMID- 25562105
TI  - Physics and chemistry of antimicrobial behavior of ion-exchanged silver in glass.
AB  - The results of a comprehensive study involving the antimicrobial activity in a
      silver ion-exchanged glass are presented. The study includes the glass
      composition, the method of incorporating silver into the glass, the effective
      concentration of the silver available at the glass surface, and the effect of the
      ambient environment. A quantitative kinetic model that includes the above factors
      in predicting the antimicrobial activity is proposed. Finally, experimental data
      demonstrating antibacterial activity against Staphylococcus aureus with
      correlation to the predicted model is shown. 

PMID- 25562106
TI  - Oxidative coupling of dichalcogenides with sodium sulfinates via copper-catalyzed
      cleavage of S-S and Se-Se bonds.
AB  - A copper-catalyzed sulfonylation of disulfides was achieved using sodium
      sulfinates in air. The reaction formed various sulfur-sulfone bonds efficiently
      and afforded thiosulfonates in good yields. Selenosulfonates could also be
      prepared with this procedure. Furthermore, both chalcogenide groups on the
      dichalcogenides were available in these reactions. 

PMID- 25562108
TI  - Integrating multiple omics to unravel mechanisms of Cyclosporin A induced
      hepatotoxicity in vitro.
AB  - In order to improve attrition rates of candidate-drugs there is a need for a
      better understanding of the mechanisms underlying drug-induced hepatotoxicity. We
      aim to further unravel the toxicological response of hepatocytes to a
      prototypical cholestatic compound by integrating transcriptomic and metabonomic
      profiling of HepG2 cells exposed to Cyclosporin A. Cyclosporin A exposure induced
      intracellular cholesterol accumulation and diminished intracellular bile acid
      levels. Performing pathway analyses of significant mRNAs and metabolites
      separately and integrated, resulted in more relevant pathways for the latter.
      Integrated analyses showed pathways involved in cell cycle and cellular
      metabolism to be significantly changed. Moreover, pathways involved in protein
      processing of the endoplasmic reticulum, bile acid biosynthesis and cholesterol
      metabolism were significantly affected. Our findings indicate that an integrated
      approach combining metabonomics and transcriptomics data derived from
      representative in vitro models, with bioinformatics can improve our understanding
      of the mechanisms of action underlying drug-induced hepatotoxicity. Furthermore,
      we showed that integrating multiple omics and thereby analyzing genes, microRNAs
      and metabolites of the opposed model for drug-induced cholestasis can give
      valuable information about mechanisms of drug-induced cholestasis in vitro and
      therefore could be used in toxicity screening of new drug candidates at an early
      stage of drug discovery. 

PMID- 25562109
TI  - Factors associated with HIV stigma and the impact of a nonrandomized multi
      component video aimed at reducing HIV stigma among a high-risk population in New
      York City.
AB  - We examined characteristics associated with HIV stigma and evaluated a multi
      component video designed to normalize HIV and reduce HIV stigma. Three pharmacies
      located in heavy, drug-active neighborhoods in New York City and registered to
      sell nonprescription syringes were trained to recruit their nonprescription
      syringe customers who inject drugs and their under/uninsured customers. Syringe
      customer participants were trained to recruit up to three of their peers. As part
      of a larger intervention to increase HIV testing, participants in two of three
      study arms viewed the "Health Screenings for Life" video and were administered
      pre/post-video surveys capturing HIV stigma. Participants in the nonvideo arm
      were administered one assessment of HIV stigma. Log-binomial regression with
      generalized estimating equations to account for clustering of peer networks was
      used to: (1) determine factors associated with HIV stigma and (2) determine
      differences in HIV stigma by study arm. A total of 716 participants were
      recruited. Factor analyses showed HIV stigma measures loading on two factors: HIV
      blame and HIV shame. After adjustment, HIV blame was positively associated with
      younger age (PR: 1.24; 95% CI: 1.07-1.43) and inversely associated with
      educational attainment (PR: 0.66; 95% CI: 0.58-0.76) and employment (PR: 0.76;
      95% CI: 0.60-0.96). HIV shame was inversely associated with educational
      attainment (PR: 0.75; 95% CI: 0.62-0.92), HIV-positive status (PR: 0.60; 95% CI:
      0.39-0.92), and injecting drugs (PR: 0.72; 95% CI: 0.54-0.94) and was positively
      associated with multiple sex partnerships (PR: 1.24; 95% CI: 1.01-1.52). Those
      who viewed the video were also less likely to report HIV blame and HIV shame,
      post-video, compared to those in the nonvideo arm. These data provide evidence of
      an association between HIV stigma and lower socioeconomic status groups, and
      between HIV stigma and HIV sexual risk. These data also provide evidence that a
      multi-component video aimed at normalizing HIV may assist in reducing HIV stigma
      in heavy, drug-active neighborhoods. 

PMID- 25562110
TI  - Whispering gallery mode lasing from hexagonal shaped layered lead iodide
      crystals.
AB  - We report on the synthesis and optical gain properties of regularly shaped lead
      iodide (PbI2) platelets with thickness ranging from 10-500 nm synthesized by
      chemical vapor deposition methods. The as-prepared single crystalline platelets
      exhibit a near band edge emission of ~ 500 nm. Whispering gallery mode (WGM)
      lasing from individual hexagonal shaped PbI2 platelets is demonstrated in the
      temperature-range of 77-210 K, where the lasing modes are supported by platelets
      as thin as 45 nm. The finite-difference time-domain simulation and the edge
      length dependent threshold confirm the planar WGM lasing mechanism in such
      hexagonal shaped PbI2 platelet. Through a comprehensive study of power-dependent
      photoluminescence (PL) and time-resolved PL spectroscopy, we ascribe the WGM
      lasing to be biexcitonic in nature. Moreover, for different thicknesses of
      platelet, the lowest lasing threshold occurs in platelets of ~ 120 nm, which
      attributes to the formation of a good Fabry-Perot resonance cavity in the
      vertical direction between the top and bottom platelet surfaces that enhances the
      reflection. Our present study demonstrates the feasibility of planar light
      sources based on layered semiconductor materials and that their thickness
      dependent threshold characteristic is beneficial for the optimization of layered
      material based optoelectronic devices.

PMID- 25562107
TI  - Genome-wide association study of short-acting beta2-agonists. A novel genome-wide
      significant locus on chromosome 2 near ASB3.
AB  - RATIONALE: beta2-Agonists are the most common form of treatment of asthma, but
      there is significant variability in response to these medications. A significant
      proportion of this responsiveness may be heritable. OBJECTIVES: To investigate
      whether a genome-wide association study (GWAS) could identify novel
      pharmacogenetic loci in asthma. METHODS: We performed a GWAS of acute
      bronchodilator response (BDR) to inhaled beta2-agonists. A total of 444,088
      single-nucleotide polymorphisms (SNPs) were examined in 724 individuals from the
      SNP Health Association Resource (SHARe) Asthma Resource Project (SHARP). The top
      50 SNPs were carried forward to replication in a population of 444 individuals.
      MEASUREMENTS AND MAIN RESULTS: The combined P value for four SNPs reached
      statistical genome-wide significance aftercorrecting for multiple comparisons.
      Combined P values for rs350729, rs1840321, rs1384918, and rs1319797 were 2.21 *
      10(-10), 5.75 * 10(-8), 9.3 * 10(-8), and 3.95 * 10(-8), respectively. The
      significant variants all map to a novel genetic region on chromosome 2 near the
      ASB3 gene, a region associated with smooth muscle proliferation. As compared with
      the wild type, the presence of the minor alleles reduced the degree of BDR by 20%
      in the original population and by a similar percentage in the confirmatory
      population. CONCLUSIONS: These GWAS findings for BDR in subjects with asthma
      suggest that a gene associated with smooth muscle proliferation may influence a
      proportion of the smooth muscle relaxation that occurs in asthma.

PMID- 25562111
TI  - Clinical features of pancreatic involvement in von Hippel-Lindau disease: a
      retrospective study of 55 cases in a single center.
AB  - BACKGROUND: von Hippel-Lindau (VHL) disease is an autosomal dominant disorder
      characterized by the development of multiple tumors in the central nervous system
      and visceral organs. In this study, we describe clinical features of pancreatic
      involvement in VHL disease, of which there have been few reported studies to
      date. METHODS: We reviewed medical records of 63 VHL patients, diagnosed at Asan
      Medical Center between January 1995 and December 2013. Demographic, genetic, and
      radiologic features, and the clinical course of VHL patients with pancreatic
      involvement were retrospectively analyzed. RESULTS: Among the 63 VHL patients, 55
      (87.4%) had VHL-associated pancreatic lesions (male: female, 31:24; median age at
      onset, 33 years; range, 12-67 years). These presented as single simple cysts (n =
      5, 9.1%), multiple simple cysts (n = 14, 25.5%), serous cystadenoma (n = 29,
      52.7%), or neuroendocrine tumors (NETs) (n = 17, 30.9%). Genetic tests were
      performed on 35 of the 55 patients (63.6%) and VHL gene mutations were observed
      in 28 of them (80%). Of the 55 patients, 11 received surgical treatment, 2
      received endoscopic ultrasonography-guided ethanol ablation therapy as local
      treatment for NET, and 42 patients were followed regularly without intervention
      (20%, 3.6%, and 76.4%, respectively). CONCLUSION: Pancreatic involvement in VHL
      disease is common, with a prevalence of 87.4%. Serial screening imaging studies
      for the early detection of VHL-associated NET are necessary in individuals at
      risk of VHL disease. A large-scale epidemiological study of VHL disease is needed
      to examine the natural course of the disease and the prognosis for pancreatic
      involvement.

PMID- 25562112
TI  - delta,epsilon-Unsaturated alpha,beta-diamino acids as building blocks for the
      asymmetric synthesis of diverse alpha,beta-diamino acids.
AB  - A building block approach for the synthesis of alpha,beta-diamino acids is
      described, which involves the diastereodivergent preparation of two sets of
      orthogonally protected delta,epsilon-unsaturated alpha,beta-diamino acids as
      templates for the preparation of 12 new alpha,beta-diamino acids of biological
      relevance using simple techniques. 

PMID- 25562113
TI  - Ailing voters advance attractive congressional candidates.
AB  - Among many benefits of facial attractiveness, there is evidence that more
      attractive politicians are more likely to be elected. Recent research found this
      effect to be most pronounced in congressional districts with high disease threat
      a result attributed to an adaptive disease avoidance mechanism, whereby the
      association of low attractiveness with poor health is particularly worrisome to
      voters who feel vulnerable to disease. We provided a more direct test of this
      explanation by examining the effects of individuals' own health and age.
      Supporting a disease avoidance mechanism, less healthy participants showed a
      stronger preference for more attractive contenders in U.S. Senate races than
      their healthier peers, and this effect was stronger for older participants, who
      were generally less healthy than younger participants. Stronger effects of health
      for older participants partly reflected the absence of positive bias toward
      attractive candidates among the healthiest, suggesting that healthy older adults
      may be unconcerned about disease threat or sufficiently wise to ignore
      attractiveness. 

PMID- 25562115
TI  - Does Internet-based cognitive behavioral therapy (iCBT) prevent major depressive
      episode for workers? A 12-month follow-up of a randomized controlled trial.
AB  - BACKGROUND: In this study we investigated whether an Internet-based computerized
      cognitive behavioral therapy (iCBT) program can decrease the risk of DSM-IV-TR
      major depressive episodes (MDE) during a 12-month follow-up of a randomized
      controlled trial of Japanese workers. METHOD: Participants were recruited from
      one company and three departments of another company. Those participants who did
      not experience MDE in the past month were randomly allocated to intervention or
      control groups (n = 381 for each). A 6-week, six-lesson iCBT program was provided
      to the intervention group. While the control group only received the usual
      preventive mental health service for the first 6 months, the control group was
      given a chance to undertake the iCBT program after a 6-month follow-up. The
      primary outcome was a new onset of DSM-IV-TR MDE during the 12-month follow-up,
      as assessed by means of the web version of the WHO Composite International
      Diagnostic Interview (CIDI), version 3.0 depression section. RESULTS: The
      intervention group had a significantly lower incidence of MDE at the 12-month
      follow-up than the control group (Log-rank chi2 = 7.04, p < 0.01). The hazard
      ratio for the intervention group was 0.22 (95% confidence interval 0.06-0.75),
      when estimated by the Cox proportional hazard model. CONCLUSIONS: The present
      study demonstrates that an iCBT program is effective in preventing MDE in the
      working population. However, it should be noted that MDE was measured by self
      report, while the CIDI can measure the episodes more strictly following DSM-IV
      criteria.

PMID- 25562116
TI  - The diagnostic utility of tumor markers: a teachable moment.

PMID- 25562117
TI  - The evolution and emergence of hantaviruses.
AB  - Hantaviruses are a major class of zoonotic pathogens and cause a variety of
      severe diseases in humans. For most of the last 50 years rodents have been
      considered to be the primary hosts of hantaviruses, with hantavirus evolution
      thought to reflect a process of virus-rodent co-divergence over a time-scale of
      millions of years, with occasional spill-over into humans. However, recent
      discoveries have revealed that hantaviruses infect a more diverse range of
      mammalian hosts, particularly Chiroptera (bats) and Soricomorpha (moles and
      shrews), and that cross-species transmission at multiple scales has played an
      important role in hantavirus evolution. As a consequence, the evolution and
      emergence of hantaviruses is more complex than previously anticipated, and may
      serve as a realistic model for other viral groups. 

PMID- 25562118
TI  - Temperature-dependent resonance energy transfer from semiconductor quantum wells
      to graphene.
AB  - Resonance energy transfer (RET) has been employed for interpreting the energy
      interaction of graphene combined with semiconductor materials such as
      nanoparticles and quantum-well (QW) heterostructures. Especially, for the
      application of graphene as a transparent electrode for semiconductor light
      emitting diodes, the mechanism of exciton recombination processes such as RET in
      graphene-semiconductor QW heterojunctions should be understood clearly. Here, we
      characterized the temperature-dependent RET behaviors in graphene/semiconductor
      QW heterostructures. We then observed the tuning of the RET efficiency from 5% to
      30% in graphene/QW heterostructures with ~60 nm dipole-dipole coupled distance at
      temperatures of 300 to 10 K. This survey allows us to identify the roles of
      localized and free excitons in the RET process from the QWs to graphene as a
      function of temperature. 

PMID- 25562119
TI  - Fabrication of individual alginate-TCP scaffolds for bone tissue engineering by
      means of powder printing.
AB  - The development of polymer-calcium phosphate composite scaffolds with tailored
      architectures and properties has great potential for bone regeneration. Herein,
      we aimed to improve the functional performance of brittle ceramic scaffolds by
      developing a promising biopolymer-ceramic network. For this purpose, two
      strategies, namely, direct printing of a powder composition consisting of a 60:40
      mixture of alpha/beta-tricalcium phosphate (TCP) powder and alginate powder or
      vacuum infiltration of printed TCP scaffolds with an alginate solution, were
      tracked. Results of structural characterization revealed that the scaffolds
      printed with 2.5 wt% alginate-modified TCP powders presented a uniformly
      distributed and interfusing alginate TCP network. Mechanical results indicated a
      significant increase in strength, energy to failure and reliability of powder
      modified scaffolds with an alginate content in the educts of 2.5 wt% when
      compared to pure TCP, as well as to TCP scaffolds containing 5 wt% or 7.5 wt% in
      the educts, in both dry and wet states. Culture of human osteoblast cells on
      these scaffolds also demonstrated a great improvement of cell proliferation and
      cell viability. While in the case of powder-mixed alginate TCP scaffolds,
      isolated alginate gels were formed between the calcium phosphate crystals, the
      vacuum-infiltration strategy resulted in the covering of the surface and internal
      pores of the TCP scaffold with a thin alginate film. Furthermore, the prediction
      of the scaffolds' critical fracture conditions under more complex stress states
      by the applied Mohr fracture criterion confirmed the potential of the powder
      modified scaffolds with 2.5 wt% alginate in the educts as structural biomaterial
      for bone tissue engineering. 

PMID- 25562120
TI  - Antibodies to early EBV, CMV, and HHV6 antigens in systemic lupus erythematosus
      patients.
AB  - OBJECTIVES: We investigated the antibody levels against early antigens of Epstein
      Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV6) in
      systemic lupus erythematosus (SLE) patients and healthy controls, and further
      correlated these antibodies to haematology/biochemistry, serology, and disease
      activity measures. METHOD: Immunoglobulin (Ig)M, IgG, and IgA levels against the
      DNA polymerase processivity factors of EBV, CMV, and HHV6, termed early antigen
      diffuse (EA/D), pp52, and p41, respectively, were determined in plasma samples
      from 77 SLE patients and 29 healthy controls by using enzyme-linked immunosorbent
      assays (ELISAs). RESULTS: IgM, IgG, and IgA levels against EBV EA/D, and IgG and
      IgA levels against CMV pp52, were significantly higher in SLE patients compared
      with healthy controls. Furthermore, EBV EA/D- and CMV pp52-directed IgG levels
      were inversely and positively associated, respectively, with lymphocyte counts in
      SLE patients. None of the findings seemed to be associated with use of
      immunosuppressive medication. CONCLUSIONS: Our results suggest strong, but
      opposite, associations of lytic EBV and CMV infections with SLE. The amplified
      humoral responses to EBV EA/D and CMV pp52 in our SLE patient cohort probably
      reflect aberrant control of EBV and CMV reactivation. However, reactivation of
      EBV appeared to correlate with lymphopenic manifestations in SLE patients whereas
      CMV reactivation seemed to correlate with increments in lymphocyte levels.

PMID- 25562121
TI  - Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil: role
      of COL1A1.
AB  - Previous studies have demonstrated a role for wound healing genes in resolution
      of cutaneous lesions caused by Leishmania spp. in both mice and humans, including
      the gene FLI1 encoding Friend leukemia virus integration 1. Reduction of Fli1
      expression in mice has been shown to result in up-regulation of collagen type I
      alpha 1 (Col1a1) and alpha 2 (Col1a2) genes and, conversely, in down-regulation
      of the matrix metalloproteinase 1 (Mmp1) gene, suggesting that Fli1 suppression
      is involved in activation of the profibrotic gene program. Here we examined
      single nucleotide polymorphisms (SNPs) in these genes as risk factors for
      cutaneous (CL) and mucosal leishmaniasis (ML), and leishmaniasis per se, caused
      by L. braziliensis in humans. SNPs were genotyped in 168 nuclear families (250
      CL; 87 ML cases) and replicated in 157 families (402 CL; 39 ML cases). Family
      based association tests (FBAT) showed the strongest association between SNPs
      rs1061237 (combined P=0.002) and rs2586488 (combined P=0.027) at COL1A1 and CL
      disease. This contributes to our further understanding of the role of wound
      healing in the resolution of CL disease, providing potential for therapies
      modulating COL1A1 via drugs acting on FLI1. 

PMID- 25562122
TI  - G1P[8] species A rotavirus over 27 years--pre- and post-vaccination eras--in
      Brazil: full genomic constellation analysis and no evidence for selection
      pressure by Rotarix(r) vaccine.
AB  - Epidemiological data on species A rotavirus (RVA) infections have demonstrated
      the genetic diversity of strains circulating worldwide. Many G and P genotype
      combinations have been described over the years, varying regionally and
      temporally, especially in developing countries. However, the most common G and P
      genotype combinations identified in RVA human strains worldwide are G1P[8],
      G2P[4], G3P[8], G4P[8] and G9P[8]. RVA genotype G1P[8] strains are responsible
      for more than 50% of child infections worldwide and component of the two vaccines
      (Rotarix(r) [RV1] and RotaTeq(r) [RV5]) licensed globally. For a better
      understanding of the evolutionary mechanisms of this genotype in Brazil,
      phylogenetic analyses based on the 11 RVA genome segments (genomic constellation)
      from 90 G1P[8] RVA strains collected in two eras - (i) pre-vaccination with RV1
      (1996-February 2006); (ii) post-vaccination (March 2006-2013) - in different
      Brazilian states were performed. The results showed the Wa-like genomic
      constellation of the Brazilian G1P[8] strains with a I1-R1-C1-M1-A1-N1-T1-E1-H1
      specificity, except for two strains (rj14055-07 and ba19030-10) that belong to a
      I1-R1-C1-M1-A1-N1-T3-E1-H1 genomic constellation, evidencing the occurrence of
      reassortment (Wa-like*AU-1-like) of the NSP3 gene. Reassortment events were also
      demonstrated between Brazilian G1P[8] strains and the RV1 vaccine strain in some
      genes in vaccinated and unvaccinated children. VP7 and VP8* antigenic site
      analysis showed that the amino acid substitutions observed in samples collected
      after the introduction of RV1 in Brazil were already detected in samples
      collected in the 1980s and 1990s, suggesting that mass Brazilian RV1 vaccination
      had no impact on the diversity observed inside antigenic sites for these two
      proteins. 

PMID- 25562123
TI  - Molecular epidemiology of echoviruses 11 and 30 in Russia: different properties
      of genotypes within an enterovirus serotype.
AB  - Over 100 known enterovirus serotypes differ in their epidemiological and
      pathogenic properties. Much less is known about variation of these features on a
      sub-serotype level, such as genotypes. Echovirus 11 (E11) and E30 are amongst the
      most frequent causative agents of aseptic meningitis. We studied the molecular
      epidemiology of these pathogens to evaluate potential epidemiological and
      pathogenic dissimilarities of their genotypes. The complete VP1 genome region was
      sequenced for 97 E11 and 62 E30 isolates collected in Russia from 2008 to 2012,
      and they were studied in comparison with all 140 E11 and 432 E30 sequences
      available in GenBank. A geographic pattern of genotype prevalence was observed
      for both types. Russian E11 isolates belonged mainly to A genotype, which is
      common in Asia, and D5, which is predominant in Europe. For E30, genotype III by
      classification of Ke et al. (2011), also termed genotype a by Bailly et al.
      (2009), was endemic in Russia from 2003 to 2012, while it was not detected in
      Europe and North America during this time. The E30 genotypes VI-B, VI-G, and VI-H
      (e, f and h) were regularly introduced from different countries, became
      predominant and vanished after no more than 4years. In addition to geographic
      patterns, E11 genotypes also differed by isolation source. Genotype A2 viruses
      were significantly more often found in sewage, compared to genotype D5 that was
      isolated from both sewage and human samples. In addition, there was evidence of a
      different capacity for international transfers among E11 GtA subclusters.

PMID- 25562124
TI  - Homologous recombination in pestiviruses: identification of three putative novel
      events between different subtypes/genogroups.
AB  - Viruses from the genus Pestivirus of the family Flaviviridae have a non
      segmented, single-stranded RNA genome and can cause diseases in animals from the
      order Artiodactyla. Homologous recombination is rarely reported in this virus
      family. To detect possible recombination events, all complete pestivirus genomes
      that are available in GenBank were screened using distinct algorithms to detect
      genetic conversions and incongruent phylogenies. Three putative recombinant
      viruses derived from recombination from different pestivirus subtypes/genogroups
      were detected: Bovine viral diarrhea virus 1 (BVDV-1) strain 3156, BVDV-2 strain
      JZ05-1 and Classical swine fever virus (CSFV) strain IND/UK/LAL-290. The present
      study demonstrated that the pestivirus classification cannot be based only on the
      analysis of one fragment of the genome because genetic conversions can lead to
      errors. The designation of the recombinant forms (RF) provides a more informative
      structure for the nomenclature of the genetic variant. The present work
      reinforces that homologous recombination occurs in pestivirus populations under
      natural replication and describes the first evidence of recombination in BVDV-2. 

PMID- 25562125
TI  - Eyes on new product development.

PMID- 25562126
TI  - Ocular pharmacokinetics of fluocinolone acetonide following Iluvien implantation
      in the vitreous humor of rabbits.
AB  - PURPOSE: The purpose of this study was to evaluate the systemic and ocular
      pharmacokinetics (PK) of fluocinolone acetonide (FAc) following administration of
      Iluvien((r)) intravitreal implants. METHODS: The FAc intravitreal implant was
      administered to rabbits in 3 doses (0.2, 0.5, and 1.0 MUg/day). The concentration
      of FAc was measured by a validated liquid chromatography-mass spectrometry/mass
      spectrometry (LC-MS/MS) method in plasma and ocular tissues at various time
      points through month 24. RESULTS: Following administration of the 0.2 MUg/day
      implant, FAc levels peaked in most tissues at day 2 or 8, reached approximate
      steady state levels by month 3 and very gradually decreased over the duration of
      the study. The FAc level in the aqueous humor was not measurable at most time
      points in the rabbit. FAc was still present in most ocular tissues at 2 years.
      The 0.5 and 1.0 MUg/day dose groups followed the same pattern through month 9.
      The elimination half lives in the tissues for which it was measurable were
      greater than 83 days. Exposure to FAc was highest in the choroid/retinal pigment
      epithelium for all doses, followed by lens and retina. CONCLUSIONS: The results
      of this study demonstrate sustained delivery of FAc from the Iluvien intravitreal
      implant in the ocular tissue of rabbits. Retina and lens FAc levels with the
      Iluvien implant were approximately 1/10 those reported with the Retisert((r))
      implant. FAc levels in the aqueous were not measureable with Iluvien where they
      were measured for 12 months with Retisert.

PMID- 25562127
TI  - Improving quality and performance in Ontario's cancer services: lessons for
      constructing a learning healthcare system.
AB  - Cancer Care Ontario as a provincial agency has undergone a significant
      transformation in the last 10 years. This paper documents a predictable crisis of
      radiotherapy capacity at the turn of the millennium, creating an imperative for
      transformative change. This transformation occurred included a divestment of
      existing cancer centers to large local host hospitals while retaining service
      obligations through a financial, quality and performance contract. The paper
      documents the simultaneous introduction of quality and access measures and the
      creation of a continuously evolving improvement panel of metrics which underpin
      the performance of local centers and population-wide reporting of Cancer Control.
      The recent successful expansion to include renal services is referenced. 

PMID- 25562128
TI  - Primary prevention - recent developments in policy and support.
AB  - The focus of Cancer Care Ontario (CCO)'s renewed prevention strategy is to
      provide evidence-based support and policy advice for risk factor reduction and
      cancer prevention. As cancer shares several key modifiable risk factors with
      other major chronic diseases, CCO's prevention efforts also benefit the goals of
      chronic disease prevention. CCO's ability to successfully provide policy advice
      is dependent on timing and the ability to respond to current and emerging policy
      and legislative issues. 

PMID- 25562129
TI  - Successes and challenges in population-based cancer screening.
AB  - Cancer Care Ontario's (CCO's) organized breast, colorectal and cervical cancer
      screening programs are in different stages of development and maturity. Headed by
      clinical and scientific leads, the programs reflect a deep understanding of how
      to design, evaluate and report on programs based on evidence and best practice.
      Guided by a CCO-Ministry of Health and Long-Term Care ("the Ministry") joint
      committee and supported by recent investments in information technology
      infrastructure, the programs provide high-quality cancer screening to Ontario's
      eligible population. 

PMID- 25562130
TI  - Strategic analytics: towards fully embedding evidence in healthcare decision
      making.
AB  - Cancer Care Ontario (CCO) has implemented multiple information technology
      solutions and collected health-system data to support its programs. There is now
      an opportunity to leverage these data and perform advanced end-to-end analytics
      that inform decisions around improving health-system performance. In 2014, CCO
      engaged in an extensive assessment of its current data capacity and capability,
      with the intent to drive increased use of data for evidence-based decision
      making. The breadth and volume of data at CCO uniquely places the organization to
      contribute to not only system-wide operational reporting, but more advanced
      modelling of current and future state system management and planning. In 2012,
      CCO established a strategic analytics practice to assist the agency's programs
      contextualize and inform key business decisions and to provide support through
      innovative predictive analytics solutions. This paper describes the
      organizational structure, services and supporting operations that have enabled
      progress to date, and discusses the next steps towards the vision of embedding
      evidence fully into healthcare decision-making.

PMID- 25562131
TI  - Integrating cancer care beyond the hospital and across the cancer pathway: a
      patient-centred approach.
AB  - Cancer patients constitute one of the most complex, diverse and growing patient
      populations in Canada. Like other high-needs patient groups, cancer patients
      desire a more integrated approach to care delivery that spans organizational and
      professional boundaries. This article provides an overview of Cancer Care
      Ontario's experience in fostering a more integrated cancer system, and describes
      the organization's emerging focus on patient-centred models of integrated care
      through the whole cancer pathway, from prevention to end-of-life care and
      survivorship. 

PMID- 25562132
TI  - Improving health equity for First Nations, Inuit and Metis people: Ontario's
      Aboriginal Cancer Strategy II.
AB  - Cancer incidence is increasing more rapidly and cancer survival is worse among
      Ontario's First Nations, Inuit and Metis (FNIM) populations than among other
      Ontarians. Cancer Care Ontario's Aboriginal Cancer Strategy II aims to reduce
      this health inequity and to improve the cancer journey and experience for FNIM
      people in Ontario. This comprehensive, multi-faceted strategy was developed and
      is being implemented with and for Aboriginal Peoples in Ontario in a way that
      honours the Aboriginal Path of Well-being. 

PMID- 25562133
TI  - Personalized medicine: CCO's vision, accomplishments and future plans.
AB  - Personalized medicine is a rapidly expanding field, with the potential to improve
      patient care. Its benefits include increasing efficiency in cancer screening,
      diagnosis and treatment through early detection, targeted therapy and identifying
      individuals with an underlying genetic risk for cancer or adverse outcomes.
      Through the work of Cancer Care Ontario (CCO)'s Pathology and Laboratory Medicine
      Program, a number of initiatives have been undertaken to support developments in
      personalized medicine. In keeping with the momentum of recent accomplishments,
      CCO has led the formation of the Personalized Medicine Steering Committee to
      develop a comprehensive provincial genetics strategy for the future of cancer
      care. 

PMID- 25562134
TI  - Implementation of an agency to improve chronic kidney disease care in Ontario:
      lessons learned by the Ontario Renal Network.
AB  - In 2009, Ontario's Ministry of Health and Long-Term Care initiated the transfer
      of oversight and coordination of chronic kidney disease (CKD) care to the Ontario
      Renal Network (ORN) under the auspices of Cancer Care Ontario (CCO). The aim was
      to replicate the quality improvement and change management practices used for
      cancer control within CKD. Much of the ORN's first three years were dedicated to
      building the infrastructure necessary to bridge the gap between provincial policy
      and clinical practice. This article explores the accomplishments, challenges and
      lessons learned over that period. The results, which are applicable to the
      management of chronic diseases in Ontario, Canada, and internationally, confirm
      that sustainable change takes time and requires strong leadership, transparency,
      accountability and communication, supported by a solid foundation of data and
      evidence. 

PMID- 25562135
TI  - The challenge of quality improvement at the system level. Whither CCO?
AB  - Cancer Care Ontario has made significant strides in the improvement of access to
      high-quality cancer care by putting in place the basic elements of
      transformation: a clear plan, reporting against this plan and clinician
      engagement. However, as our health system changes so must improvement efforts.
      Greater focus on equity and population health will require a better understanding
      of the people served. The increasing need for improvement will put a premium on
      quality improvement skills. Finally, the need to re-engineer care across the
      patient journey will require attention to integration; attention that will have
      to come from government. 

PMID- 25562136
TI  - The opportunity and strategy for quality and health-system improvement now and in
      the future.
AB  - Since 2004, Cancer Care Ontario (CCO) has played a leadership role in linking
      funding to quality of care, and in using evidence and administrative and clinical
      data to drive performance and quality improvement. This article describes how CCO
      has used its cancer and renal health system strategies to establish an
      environment of continuous health system improvement. The article also describes
      how CCO's Corporate Strategy is driving organizational improvement: evolving
      CCO's capacity and capability to drive quality and value across healthcare
      settings, and its ability to advance broader health system transformation in
      support of cancer and renal patients. 

PMID- 25562137
TI  - Transparency in metabolic network reconstruction enables scalable biological
      discovery.
AB  - Reconstructing metabolic pathways has long been a focus of active research. Now,
      draft models can be generated from genomic annotation and used to simulate
      metabolic fluxes of mass and energy at the whole-cell scale. This approach has
      led to an explosion in the number of functional metabolic network models.
      However, more models have not led to expanded coverage of metabolic reactions
      known to occur in the biosphere. Thus, there exists opportunity to reconsider the
      process of reconstruction and model derivation to better support the less
      scalable investigative processes of biocuration and experimentation. Realizing
      this opportunity to improve our knowledge of metabolism requires developing new
      tools that make reconstructions more useful by highlighting metabolic network
      knowledge limitations to guide future research. 

PMID- 25562139
TI  - Ureteroscopy Without Fluoroscopy: A Feasibility Study and Comparison with
      Conventional Ureteroscopy.
AB  - INTRODUCTION AND OBJECTIVES: Patients with urolithiasis are exposed to
      significant amounts of radiation during their initial work-up, surgical
      treatment, and follow-up. The purpose of this study was to determine the
      feasibility of performing ureteroscopy without fluoroscopy. In addition, we
      compared patients treated using a completely fluoroless ureteroscopic technique
      with a cohort of conventional ureteroscopies performed using fluoroscopy.
      MATERIALS AND METHODS: A retrospective review of 50 consecutive patients
      undergoing fluoroless ureteroscopy was performed. These procedures were performed
      by inserting guidewires and instruments using tactile feedback, direct
      visualization, and external visual cues to substitute for fluoroscopy. In
      addition, this cohort was compared with 50 conventional, fluoroscopy-guided
      ureteroscopies performed in the same time period. RESULTS: Fifty ureteroscopies
      were performed without image guidance. For this cohort, the mean operative time
      was 59.2 minutes, overall stone burden was 91.53 mm(2), complication rate was 4%,
      and repeat procedure rate was 8%. Compared with conventional ureteroscopy the
      fluoroless ureteroscopy patients had a larger stone burden (p=0.042; 91.53 vs
      56.58 mm(2)), but similar age, gender, American Society of Anesthesiologists
      (ASA) score, body-mass index, operative time, complication rate, and repeat
      procedure rate. CONCLUSIONS: This study demonstrates the feasibility and efficacy
      of the completely fluoroless ureteroscopic treatment of calculi throughout the
      entire upper urinary tract while completely removing radiation exposure to the
      patients and staff. Although this fluoroless technique may be most applicable in
      patients at highest risk for radiation exposure, such as pregnant women,
      children, and recurrent stone formers, it offers an alternative for reduction of
      radiation in all patients.

PMID- 25562138
TI  - A nexus for cellular homeostasis: the interplay between metabolic and signal
      transduction pathways.
AB  - In multicellular organisms, individual cells have evolved to sense external and
      internal cues in order to maintain cellular homeostasis and survive under
      different environmental conditions. Cells efficiently adjust their metabolism to
      reflect the abundance of nutrients, energy and growth factors. The ability to
      rewire cellular metabolism between anabolic and catabolic processes is crucial
      for cells to thrive. Thus, cells have developed, through evolution, metabolic
      networks that are highly plastic and tightly regulated to meet the requirements
      necessary to maintain cellular homeostasis. The plasticity of these cellular
      systems is tightly regulated by complex signaling networks that integrate the
      intracellular and extracellular information. The coordination of signal
      transduction and metabolic pathways is essential in maintaining a healthy and
      rapidly responsive cellular state. 

PMID- 25562140
TI  - Barriers and motivators for referral of patients with suspected lynch syndrome to
      cancer genetic services: a qualitative study.
AB  - This article explores the views of general practitioners and specialists on their
      referral of patients with suspected Lynch syndrome to cancer genetic services.
      Using a purposive maximum variation sampling strategy, we conducted semi
      structured interviews face-to-face with 28 general practitioners and specialists
      in public or private hospitals and specialist clinics between March and August
      2011. General practitioners and specialists were recruited in a major
      metropolitan area in Australia. Interview transcripts were reviewed by two
      independent researchers, and thematic analysis was performed using NVivo10
      software. The main barriers and motivators identified were: (1) clinician-related
      (e.g., familiarity with Lynch syndrome and family history knowledge); (2) patient
      related (e.g., patients' interests and personal experience with cancer); and (3)
      organizational-related (e.g., access to services, guidelines and referral
      pathway). Referral of patients with suspected Lynch syndrome to cancer genetic
      services is motivated and hindered by a range of individual, interpersonal and
      organizational factors. In order to improve the care and quality of life of
      patients and family with suspected Lynch syndrome, further research is needed to
      develop supportive tools for clinicians. 

PMID- 25562141
TI  - Physician Attitudes toward Adopting Genome-Guided Prescribing through Clinical
      Decision Support.
AB  - This study assessed physician attitudes toward adopting genome-guided prescribing
      through clinical decision support (CDS), prior to enlisting in the Clinical
      Implementation of Personalized Medicine through Electronic Health Records and
      Genomics pilot pharmacogenomics project (CLIPMERGE PGx). We developed a survey
      instrument that includes the Evidence Based Practice Attitude Scale, adapted to
      measure attitudes toward adopting genome-informed interventions (EBPAS-GII). The
      survey also includes items to measure physicians' characteristics (awareness,
      experience, and perceived usefulness), attitudes about personal genome testing
      (PGT) services, and comfort using technology. We surveyed 101 General Internal
      Medicine physicians from the Icahn School of Medicine at Mount Sinai (ISMMS). The
      majority were residency program trainees (~88%). Prior to enlisting into
      CLIPMERGE PGx, most physicians were aware of and had used decision support aids.
      Few physicians, however, were aware of and had used genome-guided prescribing.
      The majority of physicians viewed decision support aids and genotype data as
      being useful for making prescribing decisions. Most physicians had not heard of,
      but were willing to use, PGT services and felt comfortable interpreting PGT
      results. Most physicians were comfortable with technology. Physicians who
      perceived genotype data to be useful in making prescribing decisions, had more
      positive attitudes toward adopting genome-guided prescribing through CDS. Our
      findings suggest that internal medicine physicians have a deficit in their
      familiarity and comfort interpreting and using genomic information. This has
      reinforced the importance of gathering feedback and guidance from our enrolled
      physicians when designing genome-guided CDS and the importance of prioritizing
      genomic medicine education at our institutions. 

PMID- 25562142
TI  - The Use of Registries to Improve Cancer Treatment: A National Database for
      Patients Treated with Interleukin-2 (IL-2).
AB  - Registries evaluating un-randomized patients have provided valuable information
      with respect to a therapy's utility, treatment practices, and evolution over
      time. While immunotherapy for cancer has been around for more than three decades,
      data collection in the form of a registry has not been undertaken. The authors
      believe that establishing a registry to study HD IL-2 immunotherapy, which has
      been the only systemic therapy producing long term unmaintained remissions for
      advanced kidney cancer and melanoma for over 20 years, will be an important
      resource in understanding the impact of immunotherapy with HD IL-2 in a rapidly
      changing therapeutic environment. Optimizing administration and improving
      selection of appropriate patients likely to benefit from HD IL-2 immunotherapy
      are two of many benefits to be derived from this endeavor. 

PMID- 25562144
TI  - DTC-and-Me: Patient, Provider, Proteins and Regulators.
AB  - The yet-unrealized potential for more "personalized" Direct-to-Consumer (DTC)
      tests to fundamentally alter the practice and economics of healthcare is
      undeniable. However, there are also many challenges to be met, including the
      herculean task of ensuring that the information provided by such tests is
      scientifically sound and, ideally, medically actionable. We consider recent
      events in DTC testing and suggest a "thought experiment" of an approach that
      could ultimately meet the needs of patients, providers and regulatory
      authorities. 

PMID- 25562143
TI  - Predicting "heart age" using electrocardiography.
AB  - Knowledge of a patient's cardiac age, or "heart age", could prove useful to both
      patients and physicians for better encouraging lifestyle changes potentially
      beneficial for cardiovascular health. This may be particularly true for patients
      who exhibit symptoms but who test negative for cardiac pathology. We developed a
      statistical model, using a Bayesian approach, that predicts an individual's heart
      age based on his/her electrocardiogram (ECG). The model is tailored to healthy
      individuals, with no known risk factors, who are at least 20 years old and for
      whom a resting ~5 min 12-lead ECG has been obtained. We evaluated the model using
      a database of ECGs from 776 such individuals. Secondarily, we also applied the
      model to other groups of individuals who had received 5-min ECGs, including 221
      with risk factors for cardiac disease, 441 with overt cardiac disease diagnosed
      by clinical imaging tests, and a smaller group of highly endurance-trained
      athletes. Model-related heart age predictions in healthy non-athletes tended to
      center around body age, whereas about three-fourths of the subjects with risk
      factors and nearly all patients with proven heart diseases had higher predicted
      heart ages than true body ages. The model also predicted somewhat higher heart
      ages than body ages in a majority of highly endurance-trained athletes,
      potentially consistent with possible fibrotic or other anomalies recently noted
      in such individuals. 

PMID- 25562145
TI  - Cardiovascular Disease Self-Management: Pilot Testing of an mHealth Healthy
      Eating Program.
AB  - Cardiac rehabilitation (CR) is crucial in the management of cardiovascular
      disease (CVD), yet attendance is poor. Mobile technology (mHealth) offers a
      potential solution to increase reach of CR. This paper presents two development
      studies to determine mobile phone usage in adults with CVD and to evaluate the
      acceptability of an mHealth healthy eating CR program. METHODS: CR attendees were
      surveyed to determine mobile phone usage rates. A second single-subject pilot
      study investigated perceptions of a 4-week theory-based healthy eating mHealth
      program and explored pre-post changes in self-efficacy. RESULTS: 74 adults with
      CVD completed the survey (50/74 male; mean age 63 +/- 10). Nearly all had mobile
      phones (70/74; 95%) and used the Internet (69/74; 93%), and most were interested
      in receiving CR by text message (57/74; 77%). 20 participants took part in the
      healthy eating pilot study. Participants read all/most of the text messages, and
      most (19/20) thought using mobile technology was a good way to deliver the
      program. The website was not widely used as visiting the website was reported to
      be time consuming. Exploratory t-tests revealed an increase in heart healthy
      eating self-efficacy post program, in particular the environmental self-efficacy
      subset (Mean = 0.62, SD = 0.74, p = 0.001). CONCLUSIONS: Text messaging was seen
      as a simple and acceptable way to deliver nutrition information and behavior
      change strategies; however, future research is needed to determine the
      effectiveness of such programs.

PMID- 25562146
TI  - Diffusion of molecular diagnostic lung cancer tests: a survey of german
      oncologists.
AB  - This study was aimed at examining the diffusion of diagnostic lung cancer tests
      in Germany. It was motivated by the high potential of detecting and targeting
      oncogenic drivers. Recognizing that the diffusion of diagnostic tests is a
      conditio sine qua non for the success of personalized lung cancer therapies, this
      study analyzed the diffusion of epidermal growth factor receptor (EGFR) and
      anaplastic lymphoma kinase (ALK) tests in Germany. Qualitative and quantitative
      research strategies were combined in a mixed-method design. A literature review
      and subsequent Key Opinion Leader interviews identified a set of qualitative
      factors driving the diffusion process, which were then translated into an online
      survey. The survey was conducted among a sample of 961 oncologists (11.34%
      response rate). The responses were analyzed in a multiple linear regression which
      identified six statistically significant factors driving the diffusion of
      molecular diagnostic lung cancer tests: reimbursement, attitude towards R&D,
      information self-assessment, perceived attitudes of colleagues, age and test
      pathway strategies. Besides the important role of adequate reimbursement and
      relevant guidelines, the results of this study suggest that an increasing usage
      of test-pathway strategies, especially in an office-based setting, can increase
      the diffusion of molecular diagnostic lung cancer tests in the future. 

PMID- 25562147
TI  - Aberrant hepatic microRNA expression in nonalcoholic fatty liver disease.
AB  - BACKGROUND/AIM: Emerging evidence suggests that microRNA (miRNA) mediated gene
      regulation influences the maintenance of metabolic homeostasis, particularly the
      states of obesity and insulin resistance, thereby providing a potential link
      between miRNAs and nonalcoholic fatty liver disease (NAFLD). METHODS: Sprague
      Dawley rats fed a high-fat diet (HFD) were used to establish a rat model of
      NAFLD. The miRNA expression profile of liver tissues was evaluated using Illumina
      HiSeq deep sequencing. Selected miRNAs were then validated by real-time PCR at
      both 4- and 12-week time points. Furthermore, the expression levels of these
      miRNAs were assessed in HepG2 cells and human hepatocytes treated with free fatty
      acids (FFAs) and proinflammatory factors (tumour necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6). RESULTS: Our results showed that consumption of
      a HFD for 4 weeks caused simple steatosis, which progressed to steatohepatitis at
      12 weeks. miRNA deep sequencing analysis identified 44 known up-regulated miRNAs
      (fold change >1.5) and 12 down-regulated miRNAs (fold change <0.5). Among the
      abnormally expressed miRNAs, miR-200a, miR-200b, miR-200c, miR-146a, miR-146b and
      miR-152 were up-regulated both in vitro and vivo. Interestingly, the expression
      levels of these six miRNAs were increased in HepG2 cells and human hepatocytes
      after treatment with FFAs and proinflammatory factors. CONCLUSION: These findings
      suggest a critical role for miRNAs in the pathogenesis of NAFLD.

PMID- 25562148
TI  - Delivery of placenta-derived mesenchymal stem cells ameliorates ischemia induced
      limb injury by immunomodulation.
AB  - BACKGROUND: Peripheral artery disease (PAD) is a major health burden in the
      world. Stem cell-based therapy has emerged as an attractive treatment option in
      regenerative medicine. In this study, we sought to test the hypothesis that stem
      cell-based therapy can ameliorate ischemia induced limb injury. METHODS: We
      isolated mesenchymal stem cells derived from human placentas (PMSCs) and
      intramuscularly transplanted them into injured hind limbs. Treatment with PMSCs
      reduced acute muscle fibers apoptosis induced by ischemia. RESULTS: PMSC
      treatment significantly enhanced regeneration of the injured hind limb by
      reducing fibrosis and enhancing running capacity when the animals were subjected
      to treadmill training. Mechanistically, injected PMSCs can modulate acute
      inflammatory responses by reducing neutrophil and macrophage infiltration
      following limb ischemia. ELISA assays further confirmed that PMSC treatment can
      also reduce pro-inflammatory cytokines, TNF-alpha and IL-6, and enhance anti
      inflammatory cytokine, IL-10 at the injury sites. CONCLUSION: Taken together, our
      results demonstrated that PMSCs can be a potential effective therapy for
      treatment of PAD via immunomodulation.

PMID- 25562149
TI  - Mechanisms of RhoGDI2 mediated lung cancer epithelial-mesenchymal transition
      suppression.
AB  - BACKGROUND: The aim of this study was to evaluate the function of RhoGDI2 in lung
      cancer epithelial-mesenchymal transition (EMT) process and to illustrate the
      underlying mechanisms that will lead to improvement of lung cancer treatment.
      METHODS: The RhoGDI2 knock-down and overexpressing A549 cell lines were first
      constructed. The influence of RhoGDI2 on cytoskeleton in A549 cells was studied
      using two approaches: G-LISA-based Rac1 activity measurement and immunostaining
      based F-actin distribution. The expression levels of key EMT genes were analyzed
      using real time quantitative polymerase chain reaction (RT-qPCR), western blot
      and immunostaining in untreated and RhoGDI2 knock-down or overexpressing A549
      cells in both in vivo and in vitro experimental settings. RESULTS: Our study
      showed that the activity of Rac1, a key gene that is crucial for the initiation
      and metastasis of human lung adenocarcinoma, causing the redistribution of F
      actin with partial loss of cell-cell adhesions and stress fibers, was
      significantly suppressed by RhoGDI2. RhoGDI2 promoted the expression of EMT
      marker gene E-cadherin and repressed EMT promoting genes Slug, Snail, alpha-SMA
      in both A549 cells and lung and liver organs derived from the mouse models.
      Knocking-down RhoGDI2 induced abnormal morphology for lung organs. CONCLUSION:
      These findings indicate that RhoGDI2 repressed the activity of Rac1 and may be
      involved in the rearrangement of cytoskeleton in lung cancer cells. RhoGDI2
      suppresses the metastasis of lung cancer mediated through EMT by regulating the
      expression of key genes such as E-cadherin, Slug, Snail and alpha-SMA in both in
      vivo and in vitro models.

PMID- 25562150
TI  - Insulin influences autophagy response distinctively in macrophages of different
      compartments.
AB  - BACKGROUND/AIMS: Diabetes mellitus (DM) is characterized by hyperglycemia,
      associated to a lack or inefficiency of the insulin to regulate glucose
      metabolism. DM is also marked by alterations in a diversity of cellular processes
      that need to be further unraveled. In this study, we examined the autophagy
      pathway in diabetic rat macrophages before and after treatment with insulin.
      METHODS: Bone marrow-derived macrophages (BMM), bronchoalveolar lavage (BAL) and
      splenic tissue of diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 10 days)
      and control rats (physiological saline, i.v.). Some diabetic rats were given
      neutral protamine Hagedorn insulin (4 IU, s.c.) 8 h before experiments. For
      characterization of the model and evaluation of the effect of insulin on the
      autophagic process, the following analyzes were performed: (a) concentrations of
      cytokines: interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-4,
      IL-10, cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 in the BAL
      supernatant was measured by ELISA; (b) characterization of alveolar macrophage
      (AM) of the BAL as surface antigens (MHCII, pan-macrophage KiM2R, CD11b) and
      autophagic markers (protein microtubule-associated light chain (LC)3, autophagy
      protein (Atg)12 by flow cytometry and confocal microscopy (c) study of
      macrophages differentiated from the bone marrow by flow cytometry and confocal
      microscopy (d) histology of the spleen by immunohistochemistry associated with
      confocal microscopy. RESULTS: Interestingly, insulin exerted antagonistic effects
      on macrophages from different tissues. Macrophages from bronchoalveolar lavage
      (BAL) enhanced their LC3 autophagosome bound content after treatment with insulin
      whereas splenic macrophages from red pulp in diabetic rats failed to enhance
      their Atg 12 levels compared to control animals. Insulin treatment in diabetic
      rats did not change LC3 content in bone marrow derived macrophages (BMM). M1 and
      M2 macrophages behaved accordingly to the host they were derived from. Diabetic
      M1 BMM had their LC3 vesicle-bound content diminished and M2 BMM enhanced their
      LC3 levels and insulin treatment failed to rescue autophagy to control levels.
      Insulin normalizes CINC-2 level but does not modulate autophagy markers.
      CONCLUSION: Taking these results together, diabetic macrophages derived from
      different compartments show different levels of autophagy markers compared to
      healthy animals, therefore, they suffer distinctively in the absence of insulin.

PMID- 25562152
TI  - Regulatory volume decrease in neural precursor cells: taurine efflux and gene
      microarray analysis.
AB  - BACKGROUND/AIMS: Neural stem/ progenitor cells (NPCs) endure important changes in
      cell volume during growth, proliferation and migration. As a first approach to
      know about NPC response to cell volume changes, the Regulatory Volume Decrease
      (RVD) subsequent to hypotonic swelling was investigated. METHODS: NPCs obtained
      from the mesencephalon and the subventricular zone of embryonic and adult mice,
      respectively, were grown and cultured as neurospheres. Cell volume changes were
      measured by large-angle light-scattering and taurine efflux by [(3)H]-taurine.
      Expression of genes encoding molecules related to RVD was analysed using a DNA
      microarray obtained from NPC samples. RESULTS: Embryonic and adult NPCs exposed
      to osmolarity reduction (H15, H30, H40) exhibited rapid swelling followed by RVD.
      The magnitude, efficiency and pharmacological profile, of RVD and of [(3)H]
      taurine osmosensitive efflux were comparable to those found in cultured brain
      cells, astrocytes and neurons. The relative expression of genes encoding
      molecules related to volume regulation, i.e. K(+) and Cl(-) channels,
      cotransporters, exchangers and aquaporins were identified in NPCs. CONCLUSION:
      NPCs show the ability to respond to hypotonic-evoked volume changes by adaptative
      recovery processes, similar to those found in other cultured brain cells. Genes
      related to molecules involved in RVD were found expressed in NPCs.

PMID- 25562151
TI  - beta-elemene reverses chemoresistance of breast cancer via regulating MDR-related
      microRNA expression.
AB  - BACKGROUND: Multidrug resistance (MDR) directly contributes to the clinical
      failure of chemotherapy in breast cancer (BCA). beta-elemene is a natural
      antitumor drug from plants. We previously confirmed that MDR could be reversed by
      beta-elemene. In this study, we intended to investigate the reversal effect of
      beta-elemene on MDR in human BCA adriacin (Adr) -resistant MCF-7 cells (MCF
      7/Adr) and docetaxel (Doc) - resistant MCF-7 cells (MCF-7/Doc) through the gene
      regulatory network. METHODS: MTT-cytotoxic, miRNA microarray, Real-time
      quantitative PCR, Dual Luciferase Activity Assay, Western blot analysis were
      performed to investigate the impact of beta-elemene on chemo-resistant BCA cell
      suvival, and its impact on the expression of chemo-resistance specific miRNA and
      the downstream target genes PTEN and Pgp. RESULTS: Compared with the miRNAs
      expression profiles of MCF-7/Adr and MCF-7/Doc cell lines from our previous
      studies, there were 322 differentially expressed miRNAs in MCF-7/Adr and MCF
      7/Doc breast cancer cells with beta-elemene intervention (50MUM/L) for 30h, and 6
      miRNAs were significantly up-regulated and 12 miRNAs were significantly down
      regulated in both MCF-7/Adr and MCF-7/Doc. We have testified that 5 miRNA is
      related to MDR before, in this study, the expression of miR-34a, miR-222, miR-452
      and miR-29a can lead to changes of the characteristics of chemo-resistant MCF
      7/Adr and MCF-7/Doc. The PTEN expression under intervention of beta-elemene was
      significantly increased and Pgp expression under beta-elemene intervention was
      significantly decreased in both cell lines. CONCLUSIONS: beta-elemene could
      influence MDR related miRNA expression and subsequently regulate the expression
      of the target genes PTEN and Pgp, which may lead to reduction of the viability of
      the chemo-resistant breast cancer cells.

PMID- 25562153
TI  - Vascular calcification in chronic kidney disease is induced by bone morphogenetic
      protein-2 via a mechanism involving the Wnt/beta-catenin pathway.
AB  - BACKGROUND: Vascular calcification (VC), in which vascular smooth muscle cells
      (VSMCs) undergo a phenotypic transformation into osteoblast-like cells, is one of
      the emergent risk factors for the accelerated atherosclerosis process
      characteristic of chronic kidney disease (CKD). Phosphate is an important
      regulator of VC. METHODS: The expression of different smooth muscle cell or
      osteogenesis markers in response to high concentrations of phosphate or exogenous
      bone morphogenetic protein 2 (BMP-2) was examined by qRT-PCR and western blotting
      in rat VSMCs. Osteocalcin secretion was measured by radioimmunoassay.
      Differentiation and calcification of VSMCs were examined by alkaline phosphatase
      (ALP) activity assay and Alizarin staining. Short hairpin RNA-mediated silencing
      of beta-catenin was performed to examine the involvement of Wnt/beta-catenin
      signaling in VSMC calcification and osteoblastic differentiation induced by high
      phosphate or BMP-2. Apoptosis was determined by TUNEL assay and
      immunofluorescence imaging. RESULTS: BMP-2 serum levels were significantly higher
      in CKD patients than in controls. High phosphate concentrations and BMP-2 induced
      VSMC apoptosis and upregulated the expression of beta-catenin, Msx2, Runx2 and
      the phosphate cotransporter Pit1, whereas a BMP-2 neutralization antibody
      reversed these effects. Knockdown of beta-catenin abolished the effect of high
      phosphate and BMP-2 on VSMC apoptosis and calcification. CONCLUSIONS: BMP-2 plays
      a crucial role in calcium deposition in VSMCs and VC in CKD patients via a
      mechanism involving the Wnt/beta-catenin pathway.

PMID- 25562154
TI  - The SIRT 3 expression profile is associated with pathological and clinical
      outcomes in human breast cancer patients.
AB  - AIMS: To investigate the association of Sirtuin 3 (SIRT 3) expression between the
      clinical characteristics and prognosis in breast cancer patients. METHODS: 308
      female patients with histologically confirmed breast cancer were enrolled in this
      study. The SIRT 3 expressions in tumor samples were detected. All the patients
      were followed up overall survival time (OS) and disease-free survival (DFS) time.
      RESULTS: SIRT 3 expression was significantly correlated with clinical
      characteristics including lymph node metastasis, pathological grade and tumor
      size of breast cancer. SIRT 3 expression status also affected the DFS and OS of
      breast cancer. Patients with high expression of SIRT 3 had shorter DFS and OS
      than those with low expression. Univariate and multivariate Cox analyses
      confirmed that high SIRT 3 expression predicted a poor prognosis in breast cancer
      patient. In vitro study revealed that the SIRT 3 knockdown by small interfering
      RNA technique dramatically reduced the proliferation, migration and invasion of
      breast cancer cell lines. CONCLUSION: Our results suggest that SIRT 3 may serve
      as a marker for clinical feature and prognosis for breast cancer.

PMID- 25562155
TI  - CYC1 silencing sensitizes osteosarcoma cells to TRAIL-induced apoptosis.
AB  - AIMS: Osteosarcoma (OS) is an aggressive bone malignancy with poor prognosis.
      Many OS cells are resistant to apoptotic induction by tumor necrosis factor
      related apoptosis inducing ligand (TRAIL). In our previous study, we found that
      the serum level of cytochrome c1 (CYC1) is significantly higher in OS patients
      than in healthy subjects. Our aim was to investigate the effects of CYC1
      silencing on TRAIL-induced apoptosis in human OS in vitro and in vivo along with
      the underlying mechanisms. METHODS: First, we determined the expression of CYC1
      in human OS tumors and cell lines versus normal adjacent tissues and cell line.
      We then studied the effects of CYC1 silencing alone or in combination with TRAIL
      on OS cell growth and apoptosis in vitro and OS tumorigenesis in vivo. RESULTS:
      We found that CYC1 is overexpressed in human OS tissues and cell lines. CYC1
      silencing by shRNA transfection inhibits proliferation, slightly induces
      apoptosis in human OS cells in vitro, and suppresses human OS tumor growth in a
      mouse xenograft model in vivo. Additionally, CYC1 silencing sensitizes OS to
      TRAIL-induced apoptosis in vitro and in vivo. Our results also showed that CYC1
      silencing significantly reduces complex III activity and potentiates TRAIL
      induced cytochrome c release and caspase-9 activation in OS cells, suggesting
      that CYC1 silencing acts via the mitochondria-dependent apoptotic pathway.
      CONCLUSION: Taken together, our results provide evidence that CYC1 plays an
      important role in OS tumorigenesis, and modulation of CYC1 may be an effective
      strategy to potentiate OS to apoptotic induction by TRAIL.

PMID- 25562156
TI  - Ouabain increases gap junctional communication in epithelial cells.
AB  - BACKGROUND/AIMS: The finding that endogenous ouabain acts as a hormone prompted
      efforts to elucidate its physiological function. In previous studies, we have
      shown that 10 nM ouabain (i.e., a concentration within the physiological range)
      modulates cell-cell contacts such as tight junctions and apical/basolateral
      polarity. In this study, we examined whether 10 nM ouabain affects another
      important cell-cell feature: gap junction communication (GJC). METHODS: We
      employed two different approaches: 1) analysis of the cell-to-cell diffusion of
      neurobiotin injected into a particular MDCK cell (epithelial cells from dog
      kidneys) in a confluent monolayer by counting the number of neighboring cells
      reached by the probe and 2) measurement of the electrical capacitance. RESULTS:
      We found that 10 nM ouabain increase GJC by 475% within 1 hour. The Na+-K+-ATPase
      acts as a receptor of ouabain. In previous works we have shown that ouabain
      activates c-Src and ERK1/2 in 1 hour; in the present study we show that the
      inhibition of these proteins block the effect of ouabain on GJC. This increase in
      GJC does not require synthesis of new protein components, because the inhibitors
      cycloheximide and actinomycin D did not affect this phenomenon. Using silencing
      assays we also demonstrate that this ouabain-induced enhancement of GJC involves
      connexins 32 and 43. CONCLUSION: Ouabain 10 nM increases GJC in MDCK cells.

PMID- 25562157
TI  - Human breast adipose-derived stem cells transfected with the stromal cell-derived
      factor-1 receptor CXCR4 exhibit enhanced viability in human autologous free fat
      grafts.
AB  - BACKGROUND: The main complication of autologous free fat tissue transplantation
      is fat resorption and calcification due to the ischemic necrosis of fat. The
      promotion of transplant neovascularization soon after autologous free fat grafts
      may reduce these outcomes. In adulthood, stromal cell-derived factor-1 (SDF-1)
      and its membrane receptor C-X-C chemokine receptor type 4 (CXCR4) are involved in
      the homing and migration of multiple stem cell types, neovascularization, and
      cell proliferation. We hypothesized that CXCR4 may improve the long-term survival
      of free fat tissue transplants by recruiting endothelial progenitor cells (EPCs)
      and may therefore improve graft revascularization. In this study, we aimed to
      determine the effect of human breast adipose-derived stem cells (HBASCs)
      transfected with the CXCR4 gene on the survival rate of human autologous free fat
      transplants in nude mice. METHODS: Human breast adipose-derived stem cells
      (HBASCs) were expanded ex vivo for 3 passages, labeled with green fluorescent
      protein (GFP) and transfected with CXCR4 or left untransfected. Autologous fat
      tissues were mixed with the GFP-labeled, CXCR4-transfected HBASCs (group A), GFP
      labeled HBASCs (group B), the known vascularization-promoting agent VEGF (group
      C), or medium (group D) and then injected subcutaneously into 32 nude mice at 4
      spots in a random fashion. Six months later, the transplanted tissue volume and
      histology were evaluated, and neo-vascularization was quantified by counting the
      capillaries. CXCR4 and SDF-1alpha mRNA expression in the transplants was
      determined using real-time quantitative PCR analysis (qPCR). RESULTS: The data
      revealed that the control (group D) transplant volume survival was 28.3 +/- 4.5%.
      Mixing CXCR4-transfected (group A) and untransfected (group B) HBASCs
      significantly increased transplant volume survival (79.5 +/- 8.3% and 67.2 +/-
      5.9%, respectively), whereas VEGF-transfected HBASCs (group C) were less
      effective (41.2 +/- 5.1%). Histological analysis revealed that both types of
      HBASCs-treated transplants consisted predominantly of adipose tissue, unlike the
      control transplants, and also presented significantly less fat necrosis and
      fibrosis. The CXCR4-transfected HBASCs-treated transplants had a significantly
      higher capillary density than did the other transplants and showed GFP and CD31
      double-positive cells (i.e., ASCs-derived endothelial cells). The mRNA expression
      of CXCR4 and SDF-1alpha was much higher in the CXCR4-transfected HBASCs
      transplants than in the other three transplants. CONCLUSIONS: Our data
      demonstrated that HBASCs can enhance the survival and quality of transplanted
      free fat tissues. Moreover, CXCR4 transfection of these HBASCs could augment this
      effect. Stimulation of angiogenesis and decreased fat cell apoptosis due to the
      recruitment of endothelial progenitor cells (EPCs) and an increase in graft
      revascularization are potential mechanisms underlying the improved long-term
      survival of free fat transplants following CXCR4-transfected HBASCs treatment.

PMID- 25562158
TI  - Anti-fibrotic effects of Astragaloside IV in systemic sclerosis.
AB  - OBJECTIVE: To evaluate the anti-fibrotic effects of Astragaloside IV in systemic
      sclerosis. METHODS: Treated or untreated systemic sclerosis (SSc) and normal
      fibroblast isolated from corresponding pairs were utilized to detect expression
      of collagen and fibronectin by western blot, quantitative real-time RT-PCR (RT
      qPCR), immunofluorescence staining and histopathological examination. SSc mouse
      model induced by bleomycin was used to evaluate the effects of the drug in vivo.
      RESULTS: Compared to normal fibroblast (NF), the expression of collagen and
      fibronectin in SSc (SScF) dramatically increased, and this could be reduced by
      Astragaloside IV (AST) in a dose- or time-dependent manner at both protein and
      mRNA levels. Administration of Astragaloside IV consistently decreased collagen
      formation and partially restored the structure, as well as suppressing collagen
      and fibronectin expression in the skin lesions of SSc-model mice.
      Mechanistically, Astragaloside IV-induced fibrosis reduction may be due to
      deregulation of Smad 3/Fli-1, the major mediators of the fibrotic response and
      key molecules for TGF-beta signaling. Astragaloside IV also decreased the level
      of p-SMAD3 and completely blocked its relocation into the nuclei. CONCLUSION:
      Astragaloside IV attenuates fibrosis by inhibiting the TGF-beta-Smads3 axis in
      systemic sclerosis.

PMID- 25562159
TI  - Melatonin protects the esophageal epithelial barrier by suppressing the
      transcription, expression and activity of myosin light chain kinase through
      ERK1/2 signal transduction.
AB  - BACKGROUND/AIMS: Dilated intercellular space (DIS) contributes to the
      pathophysiology of gastroesophageal reflux disease (GERD). Melatonin protects the
      esophageal mucosa; however, the mechanisms underlying that protection remain
      unclear. METHODS: Transmission electron microscopy (TEM) was used to evaluate the
      intercellular spaces in the esophageal epithelium of GERD patients. The Het-1A
      monolayer barrier function was investigated by measuring transepithelial
      resistance (TER) and FITC-dextran paracellular permeation. The activity of MLCK
      was represented by MLC phosphorylation. The expression and phosphorylation of
      MLCK, MLC and ERK were examined by western blot analysis. RESULTS: The expression
      and activity of MLCK and ERK phosphorylation were increased in the esophageal
      epithelium. The increased expression and activity of MLCK was correlated with
      dilated intercellular spaces. Upon acid treatment, the Het-1A monolayer
      permeability was increased. When the Het-1A monolayer was pretreated with
      melatonin and PD98059 before the acid incubation, the permeability and the
      expression and phosphorylation of MLCK and ERK decreased. CONCLUSION: Melatonin
      protects the esophageal epithelial barrier by suppressing the transcription,
      translation and activity of MLCK through ERK1/2 signal transduction. These
      findings provide a better understanding of the potential clinical application of
      melatonin in GERD treatment.

PMID- 25562160
TI  - Desipramine ameliorates Cr(VI)-induced hepatocellular apoptosis via the
      inhibition of ceramide channel formation and mitochondrial PTP opening.
AB  - BACKGROUND: Hexavalent chromium (Cr(VI)) is a common environmental pollutant.
      Cr(VI) exposure can lead to severe damage in the liver, but the preventive
      measures to diminish Cr(VI)-induced hepatotoxicity need further study. Acid
      sphingomyelinase (ASMase) is responsible for the production of ceramide via the
      hydrolysis of sphingomyelin. The present study was designed to investigate
      effects of desipramine (DES), as an ASMase inhibitor, on Cr(VI)-induced
      hepatotoxicity. METHODS: L-02 hepatocytes were incubated with different
      concentrations of Cr(VI) for 24h, and ASMase activities and ceramide levels were
      measured. Moreover, the study investigated the role of DES played in ASMase
      activities and ceramide levels. Finally, effects of DES on mRNA and protein
      expressions of the components of mitochondrial permeability transition pore (PTP)
      and PTP opening were detected. RESULTS: The ASMase activities and ceramide
      contents increased in L-02 hepatocytes treated with Cr(VI). The results
      demonstrated that apoptosis rates, ASMase activities and ceramide content
      decreased in groups treated with the combination of DES and Cr(VI) compared to
      Cr(VI) groups. Furthermore, DES inhibited Cr(VI)-induced mitochondrial PTP
      opening by intervening the mRNA and protein expressions of the components of
      mitochondrial PTP. CONCLUSIONS: DES may exert protective effects on Cr(VI)
      induced hepatocellular apoptosis probably by inhibiting ceramide channel
      formation and mitochondrial PTP opening.

PMID- 25562161
TI  - MicroRNA-223 acts as an important regulator to Kupffer cells activation at the
      early stage of Con A-induced acute liver failure via AIM2 signaling pathway.
AB  - BACKGROUND: Acute liver failure (ALF), known as a rapid and severe clinical
      syndrome, can induce multiple organ dysfunction and failure. It was noticed that
      Kupffer cells activation at the initial phase was involved in some intense
      inflammatory responses in the pathogenesis of ALF. However, detailed regulation
      mechanism of Kupffer cells activation during ALF is still obscured. Present study
      aimed to discover the potential regulator and explore deeper information of
      Kupffer cells activation at the early stage of ALF. METHODS: The mouse model of
      ALF was established by Concanavalin A injection. Dynamic immunological statuses
      of Kupffer cells at the early stage of ALF were exhibited by detecting typical
      cytokines. The expression of inflammasome AIM2 was measured in both RNA and
      protein level. Its role of affecting Kupffer cells activation during ALF by
      inducing IL-1beta production was identified by RNA interference in vitro.
      Moreover, the expression of miR-223 in vivo was measured by q-PCR and its role in
      regulating Kupffer cells activation during Con A induced ALF was determined by
      RNAs transfection. RESULTS: Present study showed that mass production of IL-1beta
      from isolated Kupffer cells in Con A treated mice might be the main driving force
      of Kupffer cells pro-inflammatory activation during ALF. The role of AIM2 in
      affecting pro-inflammatory activation of Kupffer cells by inducing IL-1beta
      production was crucial to ALF. Further study found that miR-223 acted as a
      regulator in Kupffer cells activation at the early stage of ALF by influencing IL
      1beta production via AIM2 pathway. CONCLUSION: For the first time, this paper
      demonstrated that miR-223 acted to inhibit IL-1beta production via AIM2 pathway,
      suppressing Kupffer cells pro-inflammatory activation at the early stage of ALF.
      Thus, it played an important role in the pathogenesis of ALF.

PMID- 25562162
TI  - Tendon derived stem cells promote platelet-rich plasma healing in collagenase
      induced rat achilles tendinopathy.
AB  - BACKGROUND/AIMS: Tendon injuries are common, difficult to cure and usually healed
      with fibrosis and scar tissue. The aim of this study was to evaluate tendon
      derived stem cells (TDSCs) and platelet rich plasma (PRP) in the treatment of
      collagenase induced Achilles tendinopathy in rat. METHODS: Four and 8 weeks
      (n=18) after TDSCs, PRP, PRP with TDSC or PBS (control) injection into
      collagenase or saline (sham) injected rat Achilles tendon, tendon tissue was
      harvested and tendon quality was evaluated by histology and biomechanical
      testing. TDSCs were cultured and treated by 10% PRP, and the FAK/ERK1/2 signaling
      pathway and tenocyte-related genes were detected by western blot analysis.
      RESULTS: Compared to the control, PRP treatment resulted in better healing of
      injured tendons with improved histological outcomes and biomechanical functions.
      The addition of TDSCs to PRP treatment significantly enhanced the effects of PRP
      treatment alone. TDSC injection alone had little effect on tendon healing. PRP
      and PRP with TDSC treatments of collagenase induced tendon injuries also
      increased the mRNA and protein expression of tenocyte-related genes (type I
      collagen, SCX, Tenascin C) and activated the focal adhesion kinase (FAK) and
      extracellular-regulated kinase (ERK) 1/2 signaling pathways. Treatment of TDSCs
      in vitro with 10% PRP significantly increased the phosphorylation levels of FAK
      and ERK1/2 and the protein levels of tenocyte-related genes (Col I, SCX and
      Tenascin C). Inhibition of the FAK and ERK1/2 signaling pathways abolished the
      effect of PRP. CONCLUSION: This study concludes that PRP combined with TDSCs is
      potentially effective for the treatment of tendinopathy. The PRP induced, FAK and
      ERK1/2 dependent activation of tenocyte related genes in TDSCs in vitro suggests
      that the beneficial healing effect of the PRP with TDSC combination might occur
      by means of an improved TDSC differentiation toward the tenocyte lineage. Thus, a
      PRP with TDSC combination therapy may be clinically useful.

PMID- 25562163
TI  - TGF-beta1 promotes osteosarcoma cell migration and invasion through the miR-143
      versican pathway.
AB  - BACKGROUND & AIMS: TGF-beta1 is an abundant cytokine present in the tumour
      microenvironment. It has been shown to trigger versican expression in human
      osteosarcoma cells, which may account for the metastatic potential of these
      cells. However, the underlying mechanism of TGF-beta1-mediated metastasis remains
      unclear. The aim of this study was to evaluate the roles of versican in TGF-beta1
      induced osteosarcoma cell migration and invasion. METHODS: Sixty paired
      osteosarcoma tumour tissues and adjacent normal tissues were obtained, and the
      relationship between Enneking stage and versican expression was tested by ANOVA
      analysis. Real-time PCR or Western blot was used to detect versican, Smad and miR
      143 expression. Osteosarcoma cell migration and invasion was assessed using
      Boyden chambers. A luciferase reporter assay was employed to validate the miR-143
      versican interaction. RESULTS: Both versican isoforms, V0 and V1, were
      significantly differentially expressed in tumours at different stages. TGF-beta1
      promoted osteosarcoma cell migration and invasion in vitro by up-regulating
      versican. Furthermore, TGF-beta1 suppressed miR-143 expression through a Smad 2/3
      dependent pathway. miR-143 directly targets the versican 3'-UTR, and anti-miR-143
      or versican knockdown blocked the effects of TGF-beta1. CONCLUSION: Our results
      suggest that TGF-beta1 up-regulates versican expression by suppressing miR-143,
      and this pathway is important for osteosarcoma cell migration and invasion.

PMID- 25562165
TI  - Decreased maternal serum 2-methoxyestradiol levels are associated with the
      development of preeclampsia.
AB  - BACKGROUND: 2-methoxyestradiol (2-ME), a natural metabolite of 17beta-estradiol,
      is synthesized by catechol-O-methyltransferase (COMT). The aim of this study was
      to explore the maternal 2-ME concentration and placental COMT expression in the
      different trimesters of normal pregnancy and preeclamptic pregnancies, as well as
      the effects of 2-ME on cell proliferation and migration of HTR-8/SVneo under
      normoxic (20% O2) and hypoxic (2.5% O2) conditions. METHODS: 2-ME levels were
      examined by ELISA. COMT protein expression was analyzed by Western blot and
      immunohistochemistry. Cell proliferation and migration were measured by crystal
      violet assay and transwell system under either normoxia or hypoxia. RESULTS:
      Maternal 2-ME concentration was elevated with the progression of pregnancy, in
      contrast, 2-ME was lower in women diagnosed with mild preeclampsia (mPE; 23%) and
      severe preeclampsia (sPE; 32%) as compared with normotensive full term
      pregnancies. Meanwhile, preterm controls had lower levels of 2-ME than full term
      controls. Soluble cytoplasmic COMT (S-COMT), but not membrane-bound COMT (MB
      COMT) levels in placentas were increased by 2.5 fold in the full term vs. the
      first trimester placentas. Furthermore, 2-ME suppressed cell proliferation under
      20% O2 but not 2.5% O2, while 2-ME promoted cell migration under 2.5% but not 20%
      O2in vitro. CONCLUSION: Considering 2.5% O2 is a state more closely mimicking in
      vivo condition, these data suggest a decrease in 2-ME levels may inhibit
      trophoblast cell migration, possibly leading to PE.

PMID- 25562164
TI  - MicroRNA-212 inhibits osteosarcoma cells proliferation and invasion by down
      regulation of Sox4.
AB  - BACKGROUND: Multiple MicroRNAs (miRNAs) have been identified in the development
      and progression of osteosarcoma. However, the expression and roles of miR-212 in
      osteosarcoma remain largely undefined. METHODS: Real-time PCR assays were used to
      detect the expression of miR-212 in human osteosarcoma tissues. MiR-212 mimics
      were introduced into MG63 and U2OS cells. Bioinformatic prediction was used to
      identify the potential targets of miR-212. Protein expression analysis,
      luciferase assays and rescue assays were used to confirm the substrate of miR
      212. RESULTS: miR-212 was significantly down-regulated in human osteosarcoma
      tissues, compared with adjacent normal tissues. Introduction of miR-212 mimics
      into MG63 and U2OS cells inhibited cell proliferation and invasion. Besides, miR
      212 overexpression could also inhibit tumor growth in the nude mice.
      Additionally, bioinformatic prediction suggested that the sex-determining region
      Y-box 4 (Sox4) is a target gene of miR-212. Sox4 inhibition phenocopied the roles
      of miR-212, while restored expression of Sox4 dampened miR-212-mediated
      suppression of tumor progression. CONCLUSION: The miR-212/Sox4 interaction plays
      an important role of in the osteosarcoma progression.

PMID- 25562166
TI  - Differential immuno-reactivity to genomic DNA, RNA and mitochondrial DNA is
      associated with auto-immunity.
AB  - BACKGROUND: Circulating auto-reactive antibodies are hallmark features of auto
      immune diseases, however little is known with respect to the specificity of such
      bio-markers. In the present study, we investigated the specificity of anti
      nucleic acid antibodies in the blood of subjects with systemic lupus
      erythematosus (SLE) and healthy controls. METHODS: Sera from 12 SLE cases and 8
      controls were evaluated for immuno-reactivity to purified RNA, DNA and
      mitochondrial DNA (mtDNA) by enzyme-linked immuno-sorbent assay (ELISA). RESULTS:
      As expected, immuno-reactivity to total nucleic acids was significantly higher in
      subjects with SLE when compared to healthy controls, however a clear distinction
      was observed among the various nucleic acid sub-types, with sera from SLE
      subjects displaying the greatest immuno-reactivity to RNA followed by mtDNA and
      then total DNA. CONCLUSION: The identification of auto-reactive antibodies can
      serve as highly sensitive biomarkers, although their specificity may not always
      allow diagnostic certainty. The knowledge that auto-antibodies in subjects with
      SLE display differential immuno-reactivity may help to improve existing
      diagnostics and may lead to a better understanding of the pathogenesis of auto
      immune disorders.

PMID- 25562167
TI  - MicroRNA-302b suppresses human epithelial ovarian cancer cell growth by targeting
      RUNX1.
AB  - BACKGROUND: The microRNA (miR)-302 family functions as a tumor suppressor in
      human cancer. However, its role in epithelial ovarian carcinoma (EOC) remains
      unknown. Here, we investigated the role of miR-302b and its target gene RUNX1 in
      EOC. METHODS: The expression levels of miR-302b and RUNX1 were assessed by
      quantitative real-time PCR and western blotting. The effects of ectopic
      expression of miR-302b were evaluated by the MTT assay, colony forming assay and
      flow cytometry. RUNX1 was identified as a target of miR-302b and their
      interaction was confirmed by luciferase activity assays, RUNX1 silencing and
      overexpression of a RUNX1 mutant construct lacking the 3'UTR. The effect of miR
      302b on the suppression of tumor growth was investigated in vivo in a xenograft
      mouse model. RESULTS: MiR-302b levels were markedly decreased in EOC specimens.
      Ectopic expression of miR-302b in EOC cells inhibited cell proliferation and
      colony formation, induced G0/G1 arrest, and promoted apoptosis. RUNX1 was
      identified as a direct target of miR-302b, and knockdown of RUNX1 inhibited cell
      growth in a manner similar to miR-302b overexpression, whereas introduction of a
      3'UTR mutant of RUNX1 reversed the suppressive effect of miR-302b. Furthermore,
      miR-302b overexpression led to the inactivation of the STAT3 signaling pathway in
      EOC cells and inhibited tumor growth in a xenograft mouse model. CONCLUSIONS: MiR
      302b functions as a tumor suppressor in EOC by targeting RUNX1 and modulating the
      activity of the STAT3 signaling pathway.

PMID- 25562168
TI  - DMT1-mutant erythrocytes have shortened life span, accelerated glycolysis and
      increased oxidative stress.
AB  - BACKGROUND/AIMS: Deficiency of the divalent metal transporter 1 (DMT1) leads to
      hypochromic microcytic anemia. We have previously shown that DMT1 deficiency
      impairs erythroid differentiation and induces apoptosis of erythroid cells. Here
      we analyzed metabolic processes and survival of mature erythrocytes in order to
      address potential involvement of erythrocyte defect in the pathophysiology of the
      disease. METHODS: FACS analysis was used to determine the half-life of
      erythrocytes (CFSE fluorescence), phosphatidylserine exposure (Annexin V
      binding), cytosolic Ca(2+) (Fluo3/AM fluorescence) and reactive oxygen species
      (ROS; DCF fluorescence). Enzyme activities were determined by standard
      biochemical methods. The concentration of ATP and ADP was measured on HPLC-MS/MS.
      RESULTS: We observed an accelerated clearance of CFSE-labeled DMT1-mutant
      erythrocytes from circulating blood when compared to wild-type erythrocytes. In
      vitro, DMT1-mutant erythrocytes showed significantly increased Annexin V binding
      after exposure to hyperosmotic shock and glucose depletion. Despite exaggerated
      anti-oxidative defense, higher ROS levels were present in DMT1-mutant
      erythrocytes. Accelerated anaerobic glycolysis and reduced ATP/ADP ratio detected
      in DMT1-mutant erythrocytes indicate enhanced demand for ATP. CONCLUSIONS: We
      propose that DMT1 deficiency negatively affects metabolism and life span of
      mature erythrocytes; two other aspects of defective erythropoiesis which
      contribute to the pathophysiology of the disease.

PMID- 25562169
TI  - Stimulation of suicidal erythrocyte death by artesunate.
AB  - BACKGROUND: The artemisinin derivative artesunate is effective in the treatment
      of severe malaria and is considered for the treatment of malignancy. Artesunate
      triggers tumor cell apoptosis, an effect at least in part mediated by
      mitochondria. Even though lacking mitochondria, erythrocytes may similarly enter
      suicidal death or eryptosis, which is characterized by cell shrinkage and
      breakdown of the phospholipid asymmetry of the cell membrane with
      phosphatidylserine translocation to the erythrocyte surface. Triggers of
      eryptosis include increase of cytosolic Ca(2+)-activity ([Ca(2+)]i), ceramide
      formation, and oxidative stress. The present study explored whether artesunate
      stimulates eryptosis. METHODS: Phosphatidylserine exposure at the cell surface
      was estimated from annexin V binding, cell volume from forward scatter, [Ca(2+)]i
      from Fluo3-fluorescence, ceramide abundance from binding of specific antibodies,
      and oxidative stress from 2',7'-dichlorodihydrofluorescein-diacetate
      fluorescence. RESULTS: A 48 h exposure of human erythrocytes to artesunate
      significantly increased the percentage of annexin-V-binding cells (>= 9 ug/ml)
      without significantly influencing forward scatter. Artesunate significantly
      increased [Ca(2+)]i. The stimulation of annexin-V-binding by artesunate (15
      ug/ml) was significantly blunted but not abolished by removal of extracellular
      Ca(2+). Artesunate increased the ceramide abundance at the cell surface and the
      2',7'-dichlorodihydrofluorescein-diacetate fluorescence. CONCLUSIONS: Artesunate
      stimulates phosphatidylserine translocation at the erythrocyte cell membrane, an
      effect at least partially due to increase of [Ca(2+)]i, stimulation of ceramide
      formation and generation of oxidative stress.

PMID- 25562170
TI  - Trimetazidine protects umbilical cord mesenchymal stem cells against hypoxia and
      serum deprivation induced apoptosis by activation of Akt.
AB  - BACKGROUND: Mesenchymal stem cell (MSC) transplantation is a promising therapy
      for cardiac repair. However, the efficacy is limited by the poor viability of
      MSCs in the infarcted heart. Recent findings have implicated that trimetazidine
      (TMZ) enhanced the survival of the stem cells under various conditions. However,
      as the stem cells in these studies were animal-derived, little information is
      available about the effects of TMZ on human MSCs. Herein, we propose that TMZ may
      protect human MSCs against apoptosis induced by Hypoxia/Serum deprivation (H/SD).
      METHODS: Human umbilical cord MSCs (UC-MSCs) from Wharton's jelly were pretreated
      with 10uM TMZ of H/SD with or without the Akt inhibitor LY294002. The
      morphological changes were assessed using Hoechst 33342. Apoptosis was evaluated
      via Annexin V/PI staining; and apoptosis-related proteins were detected using
      Western-blot. Protein chip technology was used to screen for differences between
      the cell supernatants. RESULTS: TMZ had a significant protective effect against
      H/SD-induced apoptosis, accompanied by an increase in Bcl-2 and p-Akt. The TMZ
      mediated anti-apoptotic effect on MSCs could be attenuated by treatment with
      LY294002. Moreover, protein chip assays showed that TMZ treatment increased the
      paracrine functions of MSCs. CONCLUSION: Trimetazidine protects human UC-MSCs
      from H/SD-induced apoptosis via the Akt pathway and may therefore be a
      potentially useful therapeutic adjunct for transplanting MSCs into damaged heart
      after myocardial infarction.

PMID- 25562171
TI  - Stimulation of erythrocyte death by phloretin.
AB  - BACKGROUND: Phloretin, a natural component of apples, pears and strawberries, has
      previously been shown to stimulate apoptosis of nucleated cells. Erythrocytes may
      similarly enter suicidal death or eryptosis, which is characterized by cell
      shrinkage and phospholipid scrambling of the erythrocyte cell membrane with
      phosphatidylserine translocation to the erythrocyte surface. Stimulators of
      eryptosis include increase of cytosolic Ca(2+)-activity ([Ca(2+)]i), ceramide,
      ATP depletion, and activation of protein kinase C (PKC) as well as p38 mitogen
      activated protein kinase (p38 kinase). METHODS: Phosphatidylserine exposure at
      the cell surface was estimated from annexin V binding, cell volume from forward
      scatter, [Ca(2+)]i from Fluo3-fluorescence, and ceramide abundance from binding
      of specific antibodies. RESULTS: A 48 h exposure of human erythrocytes to
      phloretin significantly increased the percentage of annexin-V-binding cells
      (>=100 uM) without significantly influencing forward scatter. Phloretin did not
      significantly modify [Ca(2+)]i and the stimulation of annexin-V-binding by
      phloretin (300 uM) did not require presence of extracellular Ca(2+). Phloretin
      did not significantly modify erythrocyte ATP levels, and the effect of phloretin
      on annexin-V-binding was not significantly altered by PKC inhibitor staurosporine
      (1 uM) or p38 kinase inhibitor SB2203580 (2 uM). However, phloretin significantly
      increased the ceramide abundance at the cell surface. CONCLUSIONS: Phloretin
      stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect at
      least partially due to up-regulation of ceramide abundance.

PMID- 25562172
TI  - MiR-378 promotes the migration of liver cancer cells by down-regulating Fus
      expression.
AB  - BACKGROUND: miR-378 regulates osteoblast differentiation and participates in
      tumor cell self-renewal and chemo-resistance. However, the function of miR-378 in
      liver cancer cell migration has not been reported to date. METHODS: miR-378
      expression was examined using real-time quantitative PCR. HepG2 cell migration
      and liver cell invasion were examined using wound-healing and cell invasion
      assays. Additionally, HepG2 cell metastasis was analyzed in nude mice. RESULTS:
      miR-378 over-expression enhances HepG2 cell proliferation, migration and liver
      cell invasion. Typical metastatic lesions were found in the livers of mice
      injected with miR-378-transfected cells, and high levels of the CMV promoter were
      detected in the nodules, indicating that miR-378 promoted the metastasis of the
      tumor cells to the liver. We also demonstrated that miR-378 down-regulated Fus
      expression. CONCLUSIONS: Our results suggested that miR-378 enhanced cell
      migration and metastasis by down-regulating Fus expression.

PMID- 25562173
TI  - Gelatinases and their tissue inhibitors are associated with oxidative stress: a
      potential set of markers connected with male infertility.
AB  - The expression and activity of matrix metalloproteinases (MMPs) may be regulated
      by oxidative stress in various pathophysiological processes; therefore, the aim
      of the present study was to analyse the associations between the expression of
      the gelatinases MMP-9 and MMP-2 and their tissue inhibitors TIMP-1, TIMP-2 and
      levels of total antioxidant capacity (TAC) and advanced oxidation protein
      products (AOPP) in seminal plasma prepared for artificial insemination. Levels of
      MMPs and TIMPs were evaluated using ELISA, whereas TAC and AOPP in the seminal
      plasma of 131 childless men and 38 fertile volunteers were determined
      spectrophotometrically. Seminal MMP-9 expression was higher in childless men than
      in fertile subjects, whereas there was no significant differences in MMP-2
      expression between the analysed seminal groups. TIMP-1 and TIMP-2 expression was
      similar in all groups. However, TAC expression was significantly higher in
      infertile normozoospermic and oligozoospermic men and AOPP expression was higher
      in astheno-, oligo- and normozoospermic infertile patients than in fertile men.
      High AOPP, together with an increased MMP-9:TIMP-1 ratio alters the oxidative
      antioxidative balance of the ejaculate, thereby reducing male fertility, and
      therefore these parameters may serve as additional diagnostic markers of semen
      quality and male reproductive potential.

PMID- 25562174
TI  - Relative neuroprotective effects hyperbaric oxygen treatment and TLR4 knockout in
      a mouse model of temporary middle cerebral artery occlusion.
AB  - PURPOSE: To examine the effects of hyperbaric oxygen (HBO) therapy and knockout
      of toll-like receptor 4 (TLR4) on the outcome of temporary middle cerebral artery
      occlusion (MCAO) in a mouse model. MATERIALS AND METHODS: MCAO was induced in
      anesthetized male C57Bl/6 mice (WT) and TLR4 knockout mice (TLR4(-/-)) using an
      intra-arterial filament method. After 30 or 90 min, the filament was removed, and
      the mice were given either no treatment (WT and TLR4(-/-) groups) or HBO (WT
      only). Mice were euthanized 24 h after MCAO, and the brain infarct area was
      examined using 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS: In
      the WT group, without treatment, lesion volume was 120 +/- 13 mm(3) in the mice
      subjected to 30 min' MCAO and 173 +/- 23 mm(3) in the mice subjected to 90 min'
      MCAO. Respective values with HBO treatment were 66.5 +/- 36.7 mm(3) and 53.2 +/-
      17.2 mm(3). The difference was significant only for 90-minute MCAO (p < 0.01,
      nonparametric test). In the TLR4(-/-) group (all untreated), lesion volume was
      95.9 +/- 17.9 after 90 min of MCAO, which was significantly lower than in the
      untreated WT animals (p < 0.05, nonparametric test). CONCLUSIONS: A single
      treatment of HBO immediately after MCAO followed by 24 h' reperfusion
      significantly reduces edema and may improve perfusion. TLR4 knockout protects
      mice from MCAO damage, but to a lesser extent than HBO treatment.

PMID- 25562176
TI  - Effects of Cu on the content of chlorophylls and secondary metabolites in the Cu
      hyperaccumulator lichen Stereocaulon japonicum.
AB  - Understanding the relationship between Cu and Cu-hyperaccumulator lichens is
      important for their application in monitoring and assessing heavy metal
      pollution. We investigated the Cu-hyperaccumulator lichen Stereocaulon japonicum
      at several Cu-polluted and control sites in Japan, and found the lichen to be
      widely distributed. Its concentrations of Cu, chlorophylls, and secondary
      metabolites, chlorophyll-related indices, and absorption spectra were measured,
      and we observed negative effects of Cu on these concentrations and indices. For
      highly Cu-polluted samples (>100ppm dry weight), however, we found significant
      linear correlations between Cu and chlorophyll concentrations. This can be
      considered as the response of the photobiont in S. japonicum to Cu stress. In
      highly Cu-polluted samples the chlorophyll-related indices and concentration of
      total secondary metabolites were almost constant regardless of Cu concentration.
      This suggests that the increase in chlorophyll concentration with the increase in
      Cu concentration enhances photosynthetic productivity per unit biomass, which
      will allow the production of extra structure and energy for maintaining the
      chlorophyll-related indices under Cu stress. The relationship between the
      increase in chlorophyll concentration of S. japonicum and the decrease in
      secondary metabolite concentration of the lichen can be explained by considering
      the balance of carbohydrates in the lichen. We found that a spectral index A372
      A394 can be a useful index of the concentrations of Cu and total secondary
      metabolites in S. japonicum. These findings show the adjustment of the content of
      chlorophylls and secondary metabolites in S. japonicum to Cu stress, and provide
      a better understanding of the relationship between Cu and the Cu-hyperaccumulator
      lichen. 

PMID- 25562177
TI  - Effects of mine wastewater irrigation on activities of soil enzymes and
      physiological properties, heavy metal uptake and grain yield in winter wheat.
AB  - In China, coal-mining industries are mainly located in the water shortage areas
      including arid or semiarid areas. Mine wastewater is used for irrigation of
      agricultural land in these areas. However, few studies have been conducted to
      address ecological and food safety risks caused by mine wastewater irrigation. In
      this research, a pot experiment was performed to examine the effects of mine
      wastewater irrigation on soil enzymes, physiological properties of wheat and
      potential risks of heavy metal contamination to wheat crop. Plants were subjected
      to three mine wastewater irrigation treatments: leacheate of coal gangue (T1),
      coal-washing wastewater (T2) and precipitated coal-washing wastewater (T3).
      Plants irrigated with well water were taken as the control (CK). The results
      showed that mine wastewater irrigation caused adverse effects on soil enzymes,
      physiological properties and grain yield of winter wheat. At anthesis, T1, T2 and
      T3 treatments significantly reduced the activities of soil enzymes (urease,
      sucrase and catalase), root activity and net photosynthetic rate of wheat
      compared to CK. At maturity, grain yield was decreased by 17.8%, 15.4% and 9.8%
      by T1, T2 and T3, respectively, as compared to that of CK. Importantly, mine
      wastewater irrigation resulted in accumulation of heavy metals (Cr, Pb, Cu and
      Zn) in wheat grain. Contents of these heavy metals in grains of winter wheat
      subjected to mine wastewater irrigation were significantly higher than those in
      CK. The comprehensive contamination indexes of wheat grain in T1, T2 and T3 all
      reached high pollution level. Our results showed that mine wastewater irrigation
      significantly increased the pollution risk of heavy metals, thus unsuitable for
      crop irrigation. 

PMID- 25562175
TI  - Resting-state anticorrelations between medial and lateral prefrontal cortex:
      association with working memory, aging, and individual differences.
AB  - We examined how variation in working memory (WM) capacity due to aging or
      individual differences among young adults is associated with intrinsic or resting
      state anticorrelations, particularly between (1) the medial prefrontal cortex
      (MPFC), a component of the default-mode network (DMN) that typically decreases in
      activation during external, attention-demanding tasks, and (2) the dorsolateral
      prefrontal cortex (DLPFC), a component of the fronto-parietal control network
      that supports executive functions and WM and typically increases in activation
      during attention-demanding tasks. We compared the magnitudes of MPFC-DLPFC
      anticorrelations between healthy younger and older participants (Experiment 1)
      and related the magnitudes of these anticorrelations to individual differences on
      two behavioral measures of WM capacity in two independent groups of young adults
      (Experiments 1 and 2). Relative to younger adults, older adults exhibited
      reductions in WM capacity and in MPFC-DLPFC anticorrelations. Within younger
      adults, greater MPFC-DLPFC anticorrelation at rest correlated with greater WM
      capacity. These findings show that variation in MPFC-DLPFC anticorrelations,
      whether related to aging or to individual differences, may reflect an intrinsic
      functional brain architecture supportive of WM capacity. 

PMID- 25562178
TI  - Evolutionary relationships of iridoviruses and divergence of ascoviruses from
      invertebrate iridoviruses in the superfamily Megavirales.
AB  - The family Iridoviridae of the superfamily Megavirales currently consists of five
      genera. Three of these, Lymphocystivirus, Megalocytivirus and Ranavirus, are
      composed of species that infect vertebrates, and the other two, Chloriridovirus
      and Iridovirus, contain species that infect invertebrates. Until recently, the
      lack of genomic sequence data limited investigation of the evolutionary
      relationships between the invertebrate iridoviruses (IIVs) and vertebrate
      iridoviruses (VIVs), as well as the relationship of these viruses to those of the
      closely related family Ascoviridae, which only contains species that infect
      insects. To help clarify the phylogenetic relationships of these viruses, we
      recently published the annotated genome sequences of five additional IIV
      isolates. Here, using classical approaches of phylogeny via maximum likelihood, a
      Bayesian approach, and resolution of a core protein tree, we demonstrate that the
      invertebrate and vertebrate IV species constitute two lineages that diverged
      early during the evolution of the family Iridoviridae, before the emergence of
      the four IIV clades, previously referred to as Chloriridoviruses,
      Polyiridoviruses, Oligoiridoviruses and Crustaceoiridoviruses. In addition, we
      provide evidence that species of the family Ascoviridae have a more recent origin
      than most iridoviruses, emerging just before the differentiation between the
      Oligoiridoviruses and Crustaceoiridovirus clades. Our results also suggest that
      after emergence, based on their molecular clock, the ascoviruses evolved more
      quickly than their closest iridovirus relatives. 

PMID- 25562179
TI  - Correlates of sedentary behaviour in youths with Down syndrome: the UP&DOWN
      study.
AB  - The aim of this study was to identify potential correlates of sedentary time and
      television (TV) viewing time in youth with Down syndrome (DS). A total of 98
      adolescents with DS (63 males) aged 11-20 years old participated in this study.
      Total sedentary time was measured using accelerometers, while total TV viewing
      time and potential correlates were measured using proxy-report questionnaire.
      Analyses of covariance and a stepwise multiple linear regression were performed
      to examine correlates of total sedentary time and total TV viewing time.
      Different potential correlates were associated with total sedentary time (mother
      age, mother TV viewing time, perceived benefits of physical activity, birth order
      and having nearby shops in the neighbourhood) and total TV viewing time (father
      TV viewing time, TV viewing time with parents, family dietary habits during
      watching TV and weekend days time indoor). The identification of correlates
      associated with sedentary behaviour, principally those considered modifiable such
      as social and environmental factors, may contribute to development strategies to
      decrease sedentary behaviour in adolescents with DS and consequently promote a
      healthier lifestyle. 

PMID- 25562180
TI  - Expression and refolding of bioactive alpha-bungarotoxin V31 in E. coli.
AB  - In order to obtain bioactive alpha-bungarotoxin (alphaBtx) using recombinant
      protein technique, a codon-optimized synthetic gene was expressed in fusion with
      the N-terminal 10-His-tag and C-terminal Strep-tag in Escherichia coli. Further
      optimization through site-directed mutagenesis enabled moderate expression of the
      protein without the N-terminal His-tag or the C-terminal Strep-tag. Two such
      recombinant alphaBtx (ralphaBtx) were obtained, both with an additional
      methionine and a glycine at the N-terminal and one with (G4S1)2-Strep-tag at the
      C-terminal. The ralphaBtx proteins were refolded using a novel protocol, which
      efficiently produced final products with activity similar to its natural
      counterpart. The protocol could easily be scale up, which produced 0.3-1mg of
      pure and highly active ralphaBtx per liter of E. coli culture. 

PMID- 25562181
TI  - Molecular architecture of protein-RNA recognition sites.
AB  - The molecular architecture of protein-RNA interfaces are analyzed using a non
      redundant dataset of 152 protein-RNA complexes. We find that an average protein
      RNA interface is smaller than an average protein-DNA interface but larger than an
      average protein-protein interface. Among the different classes of protein-RNA
      complexes, interfaces with tRNA are the largest, while the interfaces with the
      single-stranded RNA are the smallest. Significantly, RNA contributes more to the
      interface area than its partner protein. Moreover, unlike protein-protein
      interfaces where the side chain contributes less to the interface area compared
      to the main chain, the main chain and side chain contributions flipped in protein
      RNA interfaces. We find that the protein surface in contact with the RNA in
      protein-RNA complexes is better packed than that in contact with the DNA in
      protein-DNA complexes, but loosely packed than that in contact with the protein
      in protein-protein complexes. Shape complementarity and electrostatic potential
      are the two major factors that determine the specificity of the protein-RNA
      interaction. We find that the H-bond density at the protein-RNA interfaces is
      similar with that of protein-DNA interfaces but higher than the protein-protein
      interfaces. Unlike protein-DNA interfaces where the deoxyribose has little role
      in intermolecular H-bonds, due to the presence of an oxygen atom at the 2'
      position, the ribose in RNA plays significant role in protein-RNA H-bonds. We
      find that besides H-bonds, salt bridges and stacking interactions also play
      significant role in stabilizing protein-nucleic acids interfaces; however, their
      contribution at the protein-protein interfaces is insignificant. 

PMID- 25562182
TI  - Graphdiyne-metal contacts and graphdiyne transistors.
AB  - Graphdiyne was prepared on a metal surface, and the preparation of devices using
      it inevitably involves its contact with metals. Using density functional theory
      with dispersion correction, we systematically studied, for the first time, the
      interfacial properties of graphdiyne that is in contact with a series of metals
      (Al, Ag, Cu, Au, Ir, Pt, Ni, and Pd). Graphdiyne forms an n-type Ohmic or quasi
      Ohmic contact with Al, Ag, and Cu, while it forms a Schottky contact with Pd, Au,
      Pt, Ni, and Ir (at the source/drain-channel interface), with high Schottky
      barrier heights of 0.21, 0.46 (n-type), 0.30, 0.41, and 0.46 (p-type) eV,
      respectively. A graphdiyne field effect transistor (FET) with Al electrodes was
      simulated using quantum transport calculations. This device exhibits an on-off
      ratio up to 10(4) and a very large on-state current of 1.3 * 10(4) mA mm(-1) in a
      10 nm channel length. Thus, a new prospect has opened up for graphdiyne in high
      performance nanoscale devices. 

PMID- 25562183
TI  - Diagnosing lung carcinomas with optical coherence tomography.
AB  - RATIONALE: Lung carcinoma diagnosis on tissue biopsy can be challenging because
      of insufficient tumor and lack of architectural information. Optical coherence
      tomography (OCT) is a high-resolution imaging modality that visualizes tissue
      microarchitecture in volumes orders of magnitude larger than biopsy. It has been
      proposed that OCT could potentially replace tissue biopsy. OBJECTIVES: We aim to
      determine whether OCT could replace histology in diagnosing lung carcinomas. We
      develop and validate OCT interpretation criteria for common primary lung
      carcinomas: adenocarcinoma, squamous cell carcinoma (SCC), and poorly
      differentiated carcinoma. METHODS: A total of 82 ex vivo tumor samples were
      included in a blinded assessment with 3 independent readers. Readers were trained
      on the OCT criteria, and applied these criteria to diagnose adenocarcinoma, SCC,
      or poorly differentiated carcinoma in an OCT validation dataset. After a 7-month
      period, the readers repeated the training and validation dataset interpretation.
      An independent pathologist reviewed corresponding histology. MEASUREMENTS AND
      MAIN RESULTS: The average accuracy achieved by the readers was 82.6% (range, 73.7
      94.7%). The sensitivity and specificity for adenocarcinoma were 80.3% (65.7
      91.4%) and 88.6% (80.5-97.6%), respectively. The sensitivity and specificity for
      SCC were 83.3% (70.0-100.0%) and 87.0% (75.0-96.5%), respectively. The
      sensitivity and specificity for poorly differentiated carcinoma were 85.7% (81.0
      95.2%) and 97.6% (92.9-100.0%), respectively. CONCLUSIONS: Although these results
      are encouraging, they indicate that OCT cannot replace histology in the diagnosis
      of lung carcinomas. However, OCT has potential to aid in diagnosing lung
      carcinomas as a complement to tissue biopsy, particularly when insufficient
      tissue is available for pathology assessment.

PMID- 25562185
TI  - Association of variation range in glycated albumin (GA) with increase but not
      decrease in plasma glucose: implication for the mechanism by which GA reflects
      glycemic excursion.
AB  - OBJECTIVES: HbA1c mainly reflects mean plasma glucose (PG), whereas glycated
      albumin (GA) reflects glycemic excursion in addition to mean PG; the mechanism of
      the difference between HbA1c and GA is unknown. We hypothesized that a transient
      increase in PG irreversibly produces stable GA unlike HbA1c. To prove this
      hypothesis, we investigated diurnal variations in PG, HbA1c, #C fraction (a
      fraction containing unstable HbA1c and modified hemoglobin on HPLC) and GA in
      diabetic patients. DESIGN AND METHODS: Sixteen diabetic patients with poor
      glycemic control were enrolled in this study. Blood sampling was performed before
      and after each meal, before bedtime, and before breakfast on the following day;
      PG, HbA1c, #C fraction, and GA were measured. The variations of these indicators
      were compared with those in PG. RESULTS: HbA1c showed almost no change regardless
      of diurnal glycemic variation. Variation range in #C fraction significantly
      correlated with variation range in PG when PG increased (R=0.746, p<0.0001) and
      decreased (R=0.271, p=0.035). On the other hand, variation range in GA
      significantly correlated with variation range in PG when PG increased (R=0.322,
      p=0.021), but not when PG decreased (R=0.090, p=0.493). CONCLUSIONS: We observed
      that variation range in GA significantly correlated with variation range in PG
      when PG increased but not when PG decreased for the first time. It is considered
      that GA reflects glycemic excursion through this phenomenon.

PMID- 25562184
TI  - Clinical, operational and economic outcomes of point-of-care blood gas analysis
      in COPD patients.
AB  - INTRODUCTION: Arterial blood gas analysis is relevant in chronic obstructive
      pulmonary disease (COPD) management. The aim of this study was to evaluate
      whether the use of a blood gas analyzer in pulmonology departments improves the
      clinical, operational and economic outcomes when compared with clinical
      laboratory measurements. PATIENTS AND METHODS: It is an observational prospective
      study. 112 patients were selected. After specimen collection, the measurement was
      performed both in pulmonology office as point-of-care and in laboratory. We
      evaluated clinical outcomes (modification of the indication of long-term oxygen
      therapy (LTOT) according to results, changes in blood gas analysis results,
      relationship of the partial pressure of oxygen (PaO2) obtained in the medical
      visit and velocity of change of the PaO2, influence of total haemoglobin
      concentration and the change in PaO2), operational outcomes (turnaround time
      (TAT) from specimen collection to receiving the blood gas analysis report) and
      economic outcomes (overall cost per process of patient care). RESULTS: There were
      discrepancies in the indication of LTOT in 13.4% of patients. All parameters
      showed changes. PaO2 levels showed changes in 2 ways, though they frequently
      increase over time. The correlation was not good in the other two clinical
      outcomes. The median TATs in pulmonology office were 1 min versus 79 in
      laboratory, with 52 min for specimen preparation and transport and 17 min for TAT
      intralaboratory. The overall cost for the 112 patients in pulmonology office and
      laboratory was 16,769.89? and 22,260.97? respectively. CONCLUSIONS: The use of a
      blood gas analyzer in a pulmonology office improves clinical, operational and
      economic outcomes when compared with clinical laboratory.

PMID- 25562186
TI  - Dynamic changes in sRAGE levels and relationship with cardiac function in STEMI
      patients.
AB  - OBJECTIVES: Soluble receptor of advanced glycation end-products (sRAGE) may be a
      predictive biomarker in coronary artery disease (CAD). Patients with acute
      myocardial infarction (AMI) have higher sRAGE levels compared to healthy
      subjects. Accordingly, the aim of this study was to investigate the dynamic
      changes in sRAGE levels during AMI and relationship with cardiac dysfunction.
      DESIGN AND METHODS: We prospectively included 80 patients with ST-elevation
      myocardial infarction (STEMI) treated with primary percutaneous coronary
      intervention (pPCI). sRAGE concentrations were measured before pPCI, immediately
      after pPCI and again on the first and second following days. Left ventricular
      ejection fraction (LVEF) was evaluated 1-3 days after the pPCI and again at a
      median of 7months by echocardiography, and infarct size was measured by cardiac
      magnetic resonance. RESULTS: sRAGE levels were high in the early phase of AMI;
      sRAGE levels significantly increased after pPCI compared with sRAGE before pPCI
      (median ratio: 1.25, 95% CI: 1.15-1.35, P<0.001), and the increase was observed
      prior to Troponin I (TnI). sRAGE levels decreased notably the first day after
      pPCI (median ratio: 0.34, 95% CI: 0.30-0.39, P<0.001). Peak sRAGE independently
      associated with long-term cardiac dysfunction estimated by LVEF (P=0.008).
      Furthermore, sRAGE measured after pPCI associated with infarct size (P=0.038).
      CONCLUSIONS: sRAGE levels were high in the early phase rather than in the days
      after AMI and pPCI. The increase in sRAGE was seen before detectable changes in
      TnI. In addition, sRAGE was independently associated with long-term cardiac
      dysfunction.

PMID- 25562187
TI  - Pharmacokinetics and pharmacodynamics of tacrolimus in liver transplant
      recipients: inside the white blood cells.
AB  - OBJECTIVES: Despite improvements in patient management and extensive use of
      therapeutic drug monitoring (TDM), the rate of acute cellular rejection (ACR)
      remains high in patients treated with tacrolimus (TAC). Moreover, some patients
      experienced ACR while their whole-blood (WB) concentrations were maintained
      within the therapeutic range meaning that TDM in WB misrepresents the drug
      effect. Thus, monitoring TAC directly inside of its effect compartment
      (intracellular concentrations) or monitoring directly the inhibitory effect on
      the target protein (calcineurin activity) could be more relevant. The aim of the
      present study was to explore, in 10 de novo liver transplant recipients, the
      relationship between TAC whole-blood concentrations, TAC intracellular
      concentrations and TAC-induced intracellular calcineurin inhibition at day 1 and
      day 7 after treatment initiation. DESIGN AND METHODS: Prospective monocentric
      observational pharmacokinetic (WB and intracellular concentrations)
      pharmacodynamic (calcineurin activity) study. RESULTS: Full intracellular TAC
      pharmacokinetic as well as calcineurin activity steady-state profiles is
      presented in the study. The main result of this study is the lack of relationship
      between TAC pharmacokinetics (WB and leukocytes) and calcineurin activity in
      leukocytes at day 1 and day 7 after the graft implantation. CONCLUSIONS: Drug
      monitoring of TAC intracellular concentrations and determination of the
      calcineurin activity are among future potential biomarkers of acute rejection in
      transplant recipients. A better knowledge of the relationship between TAC whole
      blood and intracellular concentrations and calcineurin activity appears necessary
      before planning clinical trials to evaluate their potential interest as
      predictive biomarkers.

PMID- 25562188
TI  - Quality indicators for critical international normalized ratio measurements in a
      hemostatic laboratory.
AB  - OBJECTIVE: This study aimed at reviewing the quality indicators for reporting
      critical international normalized ratio (INR) in a coagulation laboratory. DESIGN
      AND METHODS: This is a retrospective study conducted at Aga Khan University
      Hospital, hemostatic laboratory from February 2010 till January 2011. Critical
      INR was defined as >=5.0. All critical INRs were rechecked and results were
      communicated to the doctor or patient. Two quality indicators monitored were % of
      results communicated to the patient/doctor and % of results that remained
      critical after re-testing. RESULTS: During the study period, a total of 59,980
      INRs were reported. Of these 376 or 0.6% were critical. Successful communication
      of critical results to the doctor or patient was achieved in 275/376 (73.1%).
      Overall 353 or 94% (343 initial and 10 re-draw) samples had critical INR on
      repetition. Twenty five patients of the 240 warfarinized patients with critical
      INR had mild bleeding. No life threatening bleeding was observed in any patient.
      CONCLUSION: We observed poor communication for notifying critical INR results
      during the study period. Routine repeat analysis of critical INR did not alter
      results in majority of samples. The study assisted in improving communication in
      subsequent years. Further work is needed to establish evidence based upper and
      lower cutoff of critical INR. Effect of replicate analysis on turnaround time and
      accuracy of results needs evaluation.

PMID- 25562191
TI  - Using individual attributes to predict hierarchical position in a Macaca sylvanus
      group at 'La foret des singes', Rocamadour.
AB  - The Macaca genus is a biological model for animal societies, known for its social
      structuration by age, sex, and kinship. We managed to establish a mathematical
      model, through multiple regression tests, that emphasizes the relationship
      between several individual attributes (sex, age, matrilineal belonging) with
      hierarchical rank among a Barbary macaque (Macaca sylvanus) group (N=50) observed
      during 11 months at 'La foret des singes' in Rocamdour, France. We established
      two models according to sex, one for males and one for females, explaining 99.1%
      and 99.4% of the hierarchical rank variance respectively. Our study is the first
      step in studying the weight of each attribute in hierarchical structuration among
      this species and consequently the individual hierarchical rank determination.
      Such a model could be used as the basis for future comparative studies among the
      Macaca genus. 

PMID- 25562189
TI  - A role for the BDNF gene Val66Met polymorphism in schizophrenia? A comprehensive
      review.
AB  - Schizophrenia is believed to arise from complex gene-environment interactions.
      Brain-derived neurotrophic factor (BDNF) is involved in neuronal development,
      differentiation and plasticity. A functional single nucleotide polymorphism that
      results in a valine (Val) to methionine (Met) substitution at codon 66 (Val66Met)
      results in the aberrant sorting and release of mature BDNF through the activity
      dependent secretion pathway. The Val66Met polymorphism has been linked to
      impaired neurocognitive function in healthy adults, and identified as a locus of
      risk for a range of neuropsychiatric disorders including schizophrenia. Here we
      provide a comprehensive review of the relationship between the BDNF Val66Met
      polymorphism and schizophrenia, integrating evidence from the fields of genetic
      epidemiology, clinical psychiatry, behavioral neuroscience and neuroimaging. We
      argue that while the Val66Met polymorphism may not be a major risk-conferring
      agent for the development of schizophrenia per se, there is mounting evidence
      that the polymorphism modulates a range of clinical features of the illness,
      including age of onset, symptoms, therapeutic responsiveness, neurocognitive
      function and brain morphology. 

PMID- 25562190
TI  - Using hidden Markov models to characterize termite traveling behavior in tunnels
      with different curvatures.
AB  - Subterranean termites live underground and build tunnel networks to obtain food
      and nesting space. After obtaining food, termites return to their nests to
      transfer it. The efficiency of termite movement through the tunnels is directly
      connected to their survival. Tunnels should therefore be optimized to ensure
      highly efficient returns. An optimization factor that strongly affects movement
      efficiency is tunnel curvature. In the present study, we investigated traveling
      behavior in tunnels with different curvatures. We then characterized traveling
      behavior at the level of the individual using hidden Markov models (HMMs)
      constructed from the experimental data. To observe traveling behavior, we
      designed 5-cm long artificial tunnels that had different curvatures. The tunnels
      had widths (W) of 2, 3, or 4mm, and the linear distances between the two ends of
      the tunnels were (D) 20, 30, 40, or 50mm. High values of D indicate low
      curvature. We systematically observed the traveling behavior of Coptotermes
      formosanus shiraki and Reticulitermes speratus kyushuensis and measured the time
      (tau) required for a termite to pass through the tunnel. Using HMM models, we
      calculated tau for different tunnels and compared the results with the tau of
      real termites. We characterized the traveling behavior in terms of transition
      probability matrices (TPM) and emission probability matrices (EPM) of HMMs. We
      briefly discussed the construction of a sinusoidal-like tunnels in relation to
      the energy required for termites to pass through tunnels and provided suggestions
      for the development of more sophisticated HMMs to better understand termite
      foraging behavior. 

PMID- 25562192
TI  - Are owners' reports of their dogs' 'guilty look' influenced by the dogs' action
      and evidence of the misdeed?
AB  - While dog owners claim that their dogs' greeting behaviour after having performed
      a misdeed indicates the dogs' 'guilt', current experimental evidence suggests
      that dogs show these 'guilty look' behaviours as a response to being scolded by
      their owners. Given reports that 'guilty look' behaviours are shown also in the
      absence of being scolded, we investigated whether the dogs' own actions or the
      evidence of a misdeed might serve as triggering cues. We manipulated whether or
      not dogs ate a 'forbidden' food item and whether or not the food was visible upon
      the owners' return. Based on their dogs' greeting behaviour, owners stated that
      their dog had eaten the food no more than expected by chance. In addition, dogs'
      greeting behaviours were not affected by their own action or the presence or
      absence of the food. Thus, our findings do not support the hypothesis that dogs
      show the 'guilty look' in the absence of a concurrent negative reaction by their
      owners. 

PMID- 25562193
TI  - Behavioral reactions to novel food odors by intertidal hermit crabs.
AB  - Novel food items represent important food resources for generalist scavengers,
      such as intertidal hermit crabs. For animals that rely heavily on olfaction to
      mediate foraging, their first encounters with novel food items come from the
      detection of novel food odors. Although crustaceans have been shown to possess
      sensory mechanisms for processing novel odors, little is known about the level of
      stimulus reinforcement needed to maintain behavioral responses to novel food
      odors upon subsequent exposures. In the context of foraging, reinforcement of a
      novel food odor comes from feeding on the novel food item after sensory detection
      of the food item. This study tested the behavioral responses of hermit crabs to a
      novel food odor over repeated exposures both with and without stimulus
      reinforcement. The results show that stimulus reinforcement is needed for the
      animals to maintain their baseline level of behavioral responses to the novel
      food odors. Animals that were allowed to feed on the novel food item after first
      exposure (reinforced treatment) maintained strong behavioral reactions to the
      novel food odor during subsequent exposures. The behavioral reactions of animals
      that were not allowed to feed on the novel food item after first exposure
      (unreinforced treatment) rapidly declined. 

PMID- 25562194
TI  - Sex differences in a shoaling-boldness behavioral syndrome, but no link with
      aggression.
AB  - A behavioral syndrome is observed in a population when specific behaviors overlap
      at the individual level in different contexts. Here, we explore boldness and
      aggression personality spectra, the repeatability of shoaling, and possible
      associated correlations between the behaviors in a population of lab-reared
      zebrafish (Danio rerio). Our findings describe a sex-specific boldness-shoaling
      behavioral syndrome, as a link between boldness and shoaling behaviors is
      detected. The results indicate that bold males are likely to have a stronger
      shoaling propensity than shy males for unfamiliar conspecifics. Conversely, bold
      females are more likely to shoal than shy females, but only when presented with
      heterospecific individuals. Additionally, aggression does not correlate with
      boldness or shoaling propensity for either sex. A positive relationship between
      boldness and shoaling that differs by sex is contrary to most of the present
      literature, but could help to explain population dynamics and may also have
      evolutionary implications. 

PMID- 25562195
TI  - Yerba mate (Ilex paraguariensis) improves microcirculation of volunteers with
      high blood viscosity: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Elevated blood viscosity is a risk factor for atherosclerosis,
      thrombosis and other cardiovascular events. Our previous studies have suggested
      that consumption of Yerba mate tea (Ilex paraguariensis) has strong antioxidant
      and lipid-lowering properties in animals. The in vivo effects of Yerba mate on
      blood viscosity in humans, however, have not been studied. OBJECTIVE: This study
      aims to investigate the effect of Yerba mate tea on the reduction of blood
      viscosity and the improvement of microcirculatory parameters commonly regarded as
      risk factors for serious cardio and cerebrovascular disorders. METHODS: 142
      subjects with high blood viscosity were recruited in this randomized, double
      blind, placebo-controlled study. Yerba mate tea or placebo (5 g/day) was
      administered to different groups for 6 weeks. After treatment, results of
      hemorheological indexes, nailfold microcirculation, 6-keto-PGF1alpha and TXB2 and
      lipid profiles of subjects in the Yerba mate tea group were compared with those
      in the placebo-receiving group. RESULTS: Parameters of blood viscosity and
      microcirculation were improved in the subjects from the Yerba mate tea group but
      not in placebo-receiving patients. After treatment, whole blood viscosity, plasma
      viscosity and the Equation K value of erythrocyte sedimentation rate (ESRK)
      decreased significantly in the Yerba mate group. Meanwhile, shape, flow state and
      nailfold microcirculation appeared positively changed. Specifically, blood flow
      speeds accelerated gradually and nailfold weighted integral values decreased
      significantly. Moreover, the vasodilator 6-keto PGF1alpha increased while the
      thromboxane TXB2 decreased in serum samples of subjects in the Yerba mate
      receiving group. Overall, Yerba mate tea-receiving subjects saw nearly all
      measured values improve to levels comparable to those characteristic of patients
      with normal microcirculation. CONCLUSIONS: These results indicate the therapeutic
      capacity of Yerba mate tea in the treatment of high blood viscosity. Here, Yerba
      mate tea played a role in the regulation of various indexes of hemorheology,
      nailfold microcirculation, and the platelet aggregating factors 6-keto-PGF1a and
      TXB2. The regulation of these might be correlated with reduced blood viscosity
      and accelerating blood flow. Thus, Yerba mate tea may reduce some key risk
      factors of cardiovascular disease. Daily consumption of Yerba mate tea may be a
      better-tolerated option for individuals with high blood viscosity and
      microcirculatory disturbance and as such, a novel preventative strategy for
      patients at-risk for vascular disease.

PMID- 25562196
TI  - Developing urinary metabolomic signatures as early bladder cancer diagnostic
      markers.
AB  - Early detection is vital to improve the overall survival rate of bladder cancer
      (BCa) patients, yet there is a lack of a reliable urine-based assay for early
      detection of BCa. Urine metabolites represented a potential rich source of
      biomarkers for BCa. This study aimed to develop a metabolomics approach for high
      coverage discovery and identification of metabolites in urine samples. Urine
      samples from 23 early stage BCa patients and 21 healthy volunteers with minimum
      sample preparations were analyzed by a short 30 min UPLC-HRMS method. We detected
      and quantified over 9000 unique UPLC-HRMS features, which is more than four times
      than about 2000 features detected in previous urine metabolomic studies.
      Furthermore, multivariate OPLS-DA classification models were established to
      differentiate urine samples from bladder cancer cohort and normal health cohort.
      We identified three BCa-upregulated metabolites: nicotinuric acid, trehalose,
      AspAspGlyTrp, and three BCa-downregulated metabolites: inosinic acid,
      ureidosuccinic acid, GlyCysAlaLys. Finally, analysis of six post-surgery BCa
      urine samples showed that these BCa-metabolomic features reverted to normal state
      after tumor removal, suggesting that they reflected metabolomic features
      associated with BCa. ROC analyses using two linear regression models to combine
      the identified markers showed a high diagnostic performance for detecting BCa
      with AUC (area under the ROC curve) values of 0.919 to 0.934. In summary, we
      developed a high coverage metabolomic approach that has potential for biomarker
      discovery in cancers.

PMID- 25562198
TI  - ExcellmiRDB for translational genomics: a curated online resource for
      extracellular microRNAs.
AB  - A large number of studies have suggested extracellular microRNAs (microRNAs in
      biofluids) as potential noninvasive biomarkers for pathophysiological conditions
      such as cancer. However, reported differentially expressed signatures of
      extracellular miRNAs in diseases are not uniformly consistent among studies.
      Here, we present "ExcellmiRDB", a curated online database that provides
      integrated information about miRNAs levels in biofluids in a user-friendly way.
      Although many miRNA databases, including disease-oriented databases, have been
      launched before, the ExcellmiRDB is so far the only one specialized for storing
      curated data on miRNA levels in biofluid samples. At present, ExcellmiRDB has
      2773 disease-extracellular miRNAs and 1108 biofluid-extracellular miRNAs
      relationships curated from 108 articles selected from more than 600 surveyed
      PubMed abstracts. Information about 992 miRNAs, 82 diseases, 21 biofluids, 8
      species, 63 normalization reference genes, 5 techniques, 14 GEO profiles
      accession numbers, 7 human ethnic groups, and 18 compared clinical biomarkers
      have been provided in the database. A user can query ExcellmiRDB by selecting a
      disease or a miRNA or a biofluid. Additionally, the database provides two online
      network graphs to visualize and interact with the content of the database. The
      first network shows disease-extracellular miRNAs relationships, along with
      expression patterns and number of articles for a relationship. The second network
      visualizes biofluid-extracellular miRNAs relationships showing miRNAs spectrum
      across different types of biofluids. In conclusion, ExcellmiRDB is a new
      innovative resource for both academic and industrial researchers in translational
      omics who are developing miRNA biomarkers for noninvasive diagnostic or
      prognostic technologies. ExcellmiRDB is publicly available on
      www.excellmirdb.brfjaisalmer.com/.

PMID- 25562197
TI  - Proteomics analyses of Bacillus subtilis after treatment with plumbagin, a plant
      derived naphthoquinone.
AB  - Infectious diseases and increasing antibiotic resistance among diverse classes of
      microbes are global health concerns and a prime focus of omics systems science
      applications in novel drug discovery. Plumbagin is a plant-derived
      naphthoquinone, a natural product that exhibits antibacterial activity against
      gram-positive bacteria. In the present study, we investigated the antimicrobial
      effects of plumbagin against Bacillus subtilis using two complementary proteomics
      techniques: two-dimensional electrophoresis (2-DE) and isobaric tag for relative
      and absolute quantification (iTRAQ). Comparative quantitative proteomics analysis
      of plumbagin treated and untreated control samples identified differential
      expression of 230 proteins (1% FDR, 1.5 fold-change and >=2 peptides) in B.
      subtilis after plumbagin treatment. Pathway analysis involving the differentially
      expressed proteins suggested that plumbagin effectively increases heme and
      protein biosynthesis, whereas fatty acid synthesis was significantly reduced.
      Gene expression and metabolic activity assays further corroborated the proteomics
      findings. We anticipate that plumbagin blocks the cell division by altering the
      membrane permeability required for energy generation. This is the first report,
      to the best of our knowledge, offering new insights, at proteome level, for the
      putative mode(s) of action of plumbagin and attendant cellular targets in B.
      subtilis. The findings also suggest new ways forward for the modern omics-guided
      drug target discovery, building on traditional plant medicine.

PMID- 25562200
TI  - E-microsatellite markers for Centella asiatica (Gotu Kola) genome: validation and
      cross-transferability in Apiaceae family for plant omics research and
      development.
AB  - Abstract Centella asiatica (Gotu Kola) is a plant that grows in tropical swampy
      regions of the world and has important medicinal and culinary use. It is often
      considered as part of Ayurvedic medicine, traditional African medicine, and
      traditional Chinese medicine. The unavailability of genomics resources is
      significantly impeding its genetic improvement. To date, no attempt has been made
      to develop Expressed Sequence Tags (ESTs) derived Simple Sequence Repeat (SSR)
      markers (eSSRs) from the Centella genome. Hence, the present study aimed to
      develop eSSRs and their further experimental validation and cross-transferability
      of these markers in different genera of the Apiaceae family to which Centella
      belongs. An in-house pipeline was developed for the entire analyses by combining
      bioinformatics tools and perl scripts. A total of 4443 C. asiatica EST sequences
      from dbEST were processed, which generated 2617 nonredundant high quality EST
      sequences consisting 441 contigs and 2176 singletons. Out of 1776.5 kb of
      examined sequences, 417 (15.9%) ESTs containing 686 SSRs were detected with a
      density of one SSR per 2.59 kb. The gene ontology study revealed 282 functional
      domains involved in various processes, components, and functions, out of which 64
      ESTs were found to have both SSRs and functional domains. Out of 603 designed EST
      SSR primers, 18 pairs of primers were selected for validation based on the
      optimum parameter value. Reproducible amplification was obtained for six primer
      pairs in C. asiatica that were further tested for cross-transferability in nine
      other important genera/species of the Apiaceae family. Cross-transferability of
      the EST-SSR markers among the species were examined and Centella javanica showed
      highest transferability (83.3%). The study revealed six highly polymorphic EST
      SSR primers with an average PIC value of 0.95. In conclusion, these EST-SSR
      markers hold a big promise for the genomics analysis of Centella asiatica, to
      facilitate comparative map-based analyses across other related species within the
      Apiaceae family, and future marker-assisted breeding programs. To the best of our
      knowledge, this is the first report of development of EST-SSRs in Centella
      asiatica by in silico approaches, which offers a veritable potential in further
      use in plant omics research and development. 

PMID- 25562199
TI  - Robustness of equations that define molecular subtypes of glioblastoma tumors
      based on five transcripts measured by RT-PCR.
AB  - Glioblastoma (Gb) is one of the most deadly tumors. Its molecular subtypes are
      yet to be fully characterized while the attendant efforts for personalized
      medicine need to be intensified in relation to glioblastoma diagnosis, treatment,
      and prognosis. Several molecular signatures based on gene expression microarrays
      were reported, but the use of microarrays for routine clinical practice is
      challenged by attendant economic costs. Several authors have proposed
      discriminant equations based on RT-PCR. Still, the discriminant threshold is
      often incompletely described, which makes proper validation difficult. In a
      previous work, we have reported two Gb subtypes based on the expression levels of
      four genes: CHI3L1, LDHA, LGALS1, and IGFBP3. One Gb subtype presented with low
      expression of the four genes mentioned, and of MGMT in a large portion of the
      patients (with anticipated high methylation of its promoter), and mutated IDH1.
      Here, we evaluate the robustness of the equations fitted with these genes using
      RT-PCR values in a set of 64 cases and importantly, define an unequivocal
      discriminant threshold with a view to prognostic implications. We developed two
      approaches to generate the discriminant equations: 1) using the expression level
      of the four genes mentioned above, and 2) using those genes displaying the
      highest correlation with survival among the aforementioned four ones, plus MGMT,
      as an attempt to further reduce the number of genes. The ease of equations'
      applicability, reduction in cost for raw data, and robustness in terms of
      resampling-based classification accuracy warrant further evaluation of these
      equations to discern Gb tumor biopsy heterogeneity at molecular level, diagnose
      potential malignancy, and prognosis of individual patients with glioblastomas.

PMID- 25562201
TI  - Clinical utility of gene expression profiling data for clinical decision-making
      regarding adjuvant therapy in early stage, node-negative breast cancer: a case
      report.
AB  - Breast cancer is the most common malignancy among women in the United States with
      the second highest incidence of cancer-related death following lung cancer. The
      decision-making process regarding adjuvant therapy is a time intensive dialogue
      between the patient and her oncologist. There are multiple tools that help
      individualize the treatment options for a patient. Population-based analysis with
      Adjuvant! Online and genomic profiling with Oncotype DX are two commonly used
      tools in patients with early stage, node-negative breast cancer. This case report
      illustrates a situation in which the population-based prognostic and predictive
      information differed dramatically from that obtained from genomic profiling and
      affected the patient's decision. In light of this case, we discuss the benefits
      and limitations of these tools. 

PMID- 25562202
TI  - Challenges in Implementing Personalized Medicine for Lung Cancer within a
      National Healthcare System.
AB  - The traditional approach to the treatment of advanced non-small cell lung cancer
      (NSCLC) relied on the uniform use of cytotoxic chemotherapy. Over the last eight
      years, this paradigm of care has been shifting towards the use of molecularly
      targeted agents. Epidermal growth factor receptor (EGFR) mutations have emerged
      as an important biomarker for these targeted agents and multiple studies have
      shown that tyrosine kinase inhibitors (TKI) that inhibit EGFR are superior to
      traditional chemotherapy in patients possessing an EGFR mutation. Nationally
      funded health care systems face a number of challenges in implementing these
      targeted therapies, most related to the need to test for biomarkers that predict
      likelihood of benefiting from the drug. These obstacles include the challenge of
      getting a large enough tissue sample, workload of involved specialists,
      reliability of subtyping in NSCLC, differences in biomarker tests, and the
      disconnect between the funding of drugs and the related biomarker test. In order
      to improve patient outcomes, in a national healthcare system, there is a need for
      governments to accept the changing paradigm, invest in technology and build
      capacity for molecular testing to facilitate the implementation of improved
      patient care. 

PMID- 25562203
TI  - Health 2050: The Realization of Personalized Medicine through Crowdsourcing, the
      Quantified Self, and the Participatory Biocitizen.
AB  - The concepts of health and health care are moving towards the notion of
      personalized preventive health maintenance and away from an exclusive focus on
      the cure of disease. This is against the backdrop of contemporary public health
      challenges that include increasing costs, worsening outcomes, 'diabesity'
      epidemics, and anticipated physician shortages. Personalized preventive medicine
      could be critical to solving public health challenges at their causal root. This
      paper sets forth a vision and plan for the realization of preventive medicine by
      2050 and examines efforts already underway such as participatory health
      initiatives, the era of big health data, and qualitative shifts in mindset. 

PMID- 25562204
TI  - Field of genes: an investigation of sports-related genetic testing.
AB  - Sports-related genetic testing is a sector of the diverse direct-to-consumer
      (DTC) industry that has not yet been examined thoroughly by academic scholars. A
      systematic search was used to identify companies in this sector and content
      analysis of online information was performed. More than a dozen companies were
      identified. Marketing practices observed generally did not target parents for
      child testing, and marketing images were mild compared to images used in popular
      media. Information was provided at a high reading level (industry-wide Flesh
      Kincaid Grade Levels > 11). While ~75% of companies provide privacy policies and
      terms of service prior to purchase and ~40% provide scientific citations for
      their tests. 

PMID- 25562205
TI  - Efficacy and safety of low- and high-dose cariprazine in acute and mixed mania
      associated with bipolar I disorder: a double-blind, placebo-controlled study.
AB  - OBJECTIVE: This phase 3 trial evaluated the efficacy, safety, and tolerability of
      low- and high-dose cariprazine in patients meeting DSM-IV-TR criteria for acute
      manic or mixed episodes associated with bipolar I disorder. METHOD: This
      multicenter, randomized, double-blind, placebo-controlled, parallel-group,
      fixed/flexible-dose study was conducted from February 2010 to December 2011.
      Patients were randomly assigned to placebo, cariprazine 3-6 mg/d, or cariprazine
      6-12 mg/d for 3 weeks of double-blind treatment. Primary and secondary efficacy
      parameters were change from baseline to week 3 in Young Mania Rating Scale (YMRS)
      total score and Clinical Global Impressions-Severity of Illness (CGI-S) score,
      respectively. Post hoc analysis examined change from baseline to week 3 in YMRS
      single items. RESULTS: A total of 497 patients were randomized; 74% completed the
      study. The least squares mean difference (LSMD) for change from baseline to week
      3 in YMRS total score was statistically significant in favor of both cariprazine
      groups versus placebo (LSMD [95% CI]: 3-6 mg/d, -6.1 [-8.4 to -3.8]; 6-12 mg/d, 
      5.9 [-8.2, -3.6]; P < .001 [both]). Both cariprazine treatment groups showed
      statistically significant superiority to placebo on all 11 YMRS single items (all
      comparisons, P < .05). Change from baseline in CGI-S scores was statistically
      significantly greater in both cariprazine groups compared with placebo (LSMD [95%
      CI]: 3-6 mg/d, -0.6 [-0.9 to -0.4]; 6-12 mg/d, -0.6 [-0.9 to -0.3]; P < .001
      [both]). The most common (>= 5% and twice the rate of placebo) treatment-related
      adverse events for cariprazine were akathisia (both groups) and nausea,
      constipation, and tremor (6-12 mg/d only). CONCLUSIONS: Results of this study
      demonstrated that both low- and high-dose cariprazine were more effective than
      placebo in the treatment of acute manic or mixed episodes associated with bipolar
      I disorder. Cariprazine was generally well tolerated, although the incidence of
      akathisia was greater with cariprazine than with placebo. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01058668.

PMID- 25562206
TI  - Multimodal Exercise Benefits Mobility in Older Adults With Visual Impairment: A
      Preliminary Study.
AB  - Evidence-based recommendations for interventions to reduce fall risk in older
      adults with visual impairment are lacking. Adapted tango dance (Tango) and a
      balance and mobility program (FallProof) have improved mobility, balance, and
      quality of life (QOL) in individuals with movement impairment. This study
      compared the efficacy of Tango and FallProof for 32 individuals with visual
      impairment (age: M = 79.3, SD =11 [51-95 years]). Participants were assigned to
      Tango or FallProof to complete twenty, 90-min lessons within 12 weeks.
      Participants underwent assessment of balance, dual-tasking, endurance, gait, and
      vision-related QOL. The balance reactions of participants in both groups improved
      (p < .001). Endurance, cognitive dual-tasking, and vision-related QOL may have
      improved more for Tango than FallProof. Group differences and gains were
      maintained across time. Both programs could be effective options for motor
      rehabilitation for older adults with visual impairment because they may improve
      mobility and QOL while reducing fall risk. 

PMID- 25562207
TI  - Emodin induces neurite outgrowth through PI3K/Akt/GSK-3beta-mediated signaling
      pathways in Neuro2a cells.
AB  - In this study, a neurite outgrowth-inducing substance was isolated from the
      ethylacetate extract of the Polygonum multiflorum roots and identified as emodin
      by gas-liquid chromatography-mass spectrometry and (1)H NMR and (13)C NMR. Emodin
      displayed remarkable neurite outgrowth-inducing activity in Neuro2a cells, as
      demonstrated by morphological changes and immunocytochemistry for class III beta
      tubulin. Emodin exhibited a stronger neutrophic activity than retinoic acid (RA)
      known as inducer of neurite outgrowth in Neuro2a cells. Emodin treatment resulted
      in marked increases in phosphorylation of Akt a direct downstream signaling
      molecule of phosphatidylinositol 3-kinase (PI3K), but upstream of glycogen
      synthase kinase-3beta (GSK-3beta) and cAMP response element-binding protein
      (CREB). These augmentations and neurite-bearing cells induced by emodin were
      remarkably reduced by the addition of PI3K inhibitor LY294002. These results
      demonstrate that emodin induces neuronal differentiation of Neuro2a cells via
      PI3K/Akt/GSK-3beta pathway. 

PMID- 25562208
TI  - Bactobolin A binds to a site on the 70S ribosome distinct from previously seen
      antibiotics.
AB  - The ribosome is the target of a large number of antibiotics. Here, we report a
      3.4-A-resolution crystal structure of bactobolin A bound to 70S ribosome-tRNA
      complex. The antibiotic binds at a previously unseen site in the 50S subunit and
      displaces tRNA bound at the P-site. It thus likely has a similar mechanism of
      action as blasticidin S despite binding to a different site. The structure also
      rationalizes previously identified resistance mutations.

PMID- 25562209
TI  - Oligosaccharide and substrate binding in the starch debranching enzyme barley
      limit dextrinase.
AB  - Complete hydrolytic degradation of starch requires hydrolysis of both the alpha
      1,4- and alpha-1,6-glucosidic bonds in amylopectin. Limit dextrinase (LD) is the
      only endogenous barley enzyme capable of hydrolyzing the alpha-1,6-glucosidic
      bond during seed germination, and impaired LD activity inevitably reduces the
      maltose and glucose yields from starch degradation. Crystal structures of barley
      LD and active-site mutants with natural substrates, products and substrate
      analogues were sought to better understand the facets of LD-substrate
      interactions that confine high activity of LD to branched maltooligosaccharides.
      For the first time, an intact alpha-1,6-glucosidically linked substrate spanning
      the active site of a LD or pullulanase has been trapped and characterized by
      crystallography. The crystal structure reveals both the branch and main-chain
      binding sites and is used to suggest a mechanism for nucleophilicity enhancement
      in the active site. The substrate, product and analogue complexes were further
      used to outline substrate binding subsites and substrate binding restraints and
      to suggest a mechanism for avoidance of dual alpha-1,6- and alpha-1,4-hydrolytic
      activity likely to be a biological necessity during starch synthesis. 

PMID- 25562211
TI  - Discovery of protein- and DNA-imperceptible nanoparticle hard coating using gel
      based reaction tuning.
AB  - The seemingly inevitable protein corona appears to be an insurmountable obstacle
      to wider application of functional nanomaterials in biotechnology. The
      accumulation of serum proteins can block targeting functionalities and alter the
      in vivo fate of these nanomaterials. Here we demonstrate a method to generate non
      stick, robustly passivated functional nanoparticles (NPs) using a tailored silica
      coating. We apply agarose gel electrophoresis to sensitively evaluate protein
      binding to NPs with different surface chemistry. Using gel banding and
      retardation as a read-out for protein adsorption, we optimize the surface
      chemistry to yield a mixed charge surface which displays remarkable binding
      resistance to a wide range of serum proteins and nucleic acids. The hard silica
      shell also protects the functional NP core in harsh environments (down to pH 1)
      while still showing the ability to be targeted for cellular uptake with little or
      no non-specific binding. 

PMID- 25562212
TI  - Counting quantum dot aggregates for the detection of biotinylated proteins.
AB  - We develop a method to quantify the quantum dots (QDs) in QD aggregates in
      aqueous solution by recording the entire process of blue shifting and
      photobleaching under continuous illumination and utilize this method to detect
      the biotinylated proteins based on counting the degree of aggregation (DOA). 

PMID- 25562210
TI  - Intrinsically disordered C-terminal tails of E. coli single-stranded DNA binding
      protein regulate cooperative binding to single-stranded DNA.
AB  - The homotetrameric Escherichia coli single-stranded DNA binding protein (SSB)
      plays a central role in DNA replication, repair and recombination. E. coli SSB
      can bind to long single-stranded DNA (ssDNA) in multiple binding modes using all
      four subunits [(SSB)65 mode] or only two subunits [(SSB)35 binding mode], with
      the binding mode preference regulated by salt concentration and SSB binding
      density. These binding modes display very different ssDNA binding properties with
      the (SSB)35 mode displaying highly cooperative binding to ssDNA. SSB tetramers
      also bind an array of partner proteins, recruiting them to their sites of action.
      This is achieved through interactions with the last 9 amino acids (acidic tip) of
      the intrinsically disordered linkers (IDLs) within the four C-terminal tails
      connected to the ssDNA binding domains. Here, we show that the amino acid
      composition and length of the IDL affects the ssDNA binding mode preferences of
      SSB protein. Surprisingly, the number of IDLs and the lengths of individual IDLs
      together with the acidic tip contribute to highly cooperative binding in the
      (SSB)35 binding mode. Hydrodynamic studies and atomistic simulations suggest that
      the E. coli SSB IDLs show a preference for forming an ensemble of globular
      conformations, whereas the IDL from Plasmodium falciparum SSB forms an ensemble
      of more extended random coils. The more globular conformations correlate with
      cooperative binding. 

PMID- 25562213
TI  - Clinical ethics consultation: a need for evidence.

PMID- 25562214
TI  - Ethical obligations and clinical goals in end-of-life care: deriving a quality-of
      life construct based on the Islamic concept of accountability before God
      (taklif).
AB  - End-of-life medical decision making presents a major challenge to patients and
      physicians alike. In order to determine whether it is ethically justifiable to
      forgo medical treatment in such scenarios, clinical data must be interpreted
      alongside patient values, as well as in light of the physician's ethical
      commitments. Though much has been written about this ethical issue from religious
      perspectives (especially Christian and Jewish), little work has been done from an
      Islamic point of view. To fill the gap in the literature around Islamic
      bioethical perspectives on the matter, we derive a theologically rooted rubric
      for goals of care. We use the Islamic obligation for Muslims to seek medical
      treatment as the foundation for determining the clinical conditions under which
      Muslim physicians have a duty to treat. We next link the theological concept of
      accountability before God (taklif) to quality-of-life assessment. Using this
      construct, we suggest that a Muslim physician is not obligated to maintain or
      continue clinical treatment when patients who were formerly of, or had the
      potential to be, mukallaf (the term for a person who has taklif), are now not
      expected to regain that status by means of continued clinical treatment. 

PMID- 25562215
TI  - The determination of quality of life and medical futility in disorders of
      consciousness: reinterpreting the moral code of Islam.

PMID- 25562216
TI  - Islamic theology's contribution to medical decision making in end-of-life care.

PMID- 25562217
TI  - Exploring a new concept at the end of life: accountability before god (mukallaf).

PMID- 25562218
TI  - Normativity of heterogeneity in clinical ethics.

PMID- 25562219
TI  - Precaution (ihtiyat): do not proceed.

PMID- 25562220
TI  - A worrisome misappropriation of "mukallaf" in life-sustaining treatment.

PMID- 25562221
TI  - Islamic bioethics at the end of life: why mukallaf status cannot be the criterion
      of defining the life that should be saved.

PMID- 25562222
TI  - Neglected ends: clinical ethics consultation and the prospects for closure.
AB  - Clinical ethics consultations (CECs) are sometimes deemed complete at the moment
      when the consultants make a recommendation. In CECs that involve actual ethical
      conflict, this view of a consult's endpoint runs the risk of overemphasizing the
      conflict's resolution at the expense of the consult's process, which can have
      deleterious effects on the various parties in the conflict. This overly narrow
      focus on reaching a decision or recommendation in consults that involve profound
      moral disagreement can result in two types of adverse, lingering sequelae: moral
      distress or negative moral emotions. The problem, succinctly named, is that such
      consults have insufficient "closure" for patients, families, and providers. To
      promote closure, and avoid the ills of moral distress and the moral emotions, I
      argue that CECs need to prioritize assisted conversation between the different
      stakeholders in these conflicts, what is often referred to as "bioethics
      mediation." 

PMID- 25562223
TI  - An ethicist's scope of practice: equipping stakeholders for closure.

PMID- 25562224
TI  - Moral distress and prospects for closure.

PMID- 25562225
TI  - Power hierarchy and epistemic injustice in clinical ethics consultation.

PMID- 25562226
TI  - Beyond the recommendation: discerning achievable goals in clinical ethics
      consultation.

PMID- 25562227
TI  - Closure but no cigar.

PMID- 25562228
TI  - Attend to the middle.

PMID- 25562229
TI  - What "the straw man" teaches us, or, finding wisdom between the horns of a false
      dilemma about ethics consultation methodology.

PMID- 25562230
TI  - Beyond recommendation and mediation: moral case deliberation as moral learning in
      dialogue.

PMID- 25562231
TI  - Intensified conflict instead of closure: clinical ethics consultants'
      recommendations' potential to exacerbate ethical conflicts.

PMID- 25562232
TI  - Realistic goals and expectations for clinical ethics consultations: we should not
      overstate what we can deliver.

PMID- 25562233
TI  - Philosophical counseling as an alternative process to bioethics mediation.

PMID- 25562234
TI  - Facilitated discussion: good and good for you.

PMID- 25562235
TI  - Shared language and moral sensibility in resolving clinical ethics conflicts.

PMID- 25562236
TI  - Clinical ethics: case reports, consultations, commentaries.

PMID- 25562237
TI  - When a patient says "no".

PMID- 25562238
TI  - Accepting refusal of life-sustaining treatment: how high should the bar be?

PMID- 25562239
TI  - Getting to "yes" when the patient says "no".

PMID- 25562240
TI  - Return to Lonesome Dove: when the patient wants to go home without surgery.

PMID- 25562241
TI  - Emergent ethics consultation requested from the operating room.

PMID- 25562242
TI  - A risky recommendation.

PMID- 25562243
TI  - Preventing the predictable.

PMID- 25562244
TI  - Leading medicine through "bloodless" transplantation.

PMID- 25562245
TI  - Islamic goals for clinical treatment at the end of life: the concept of
      accountability before God (taklif) remains useful: response to open peer
      commentaries on "Ethical obligations and clinical goals in end-of-life care:
      deriving a quality-of-life construct based on the Islamic concept of
      accountability before God (taklif)".

PMID- 25562246
TI  - Response to open peer commentaries on "Neglected ends: clinical ethics
      consultation and the prospects for closure".

PMID- 25562250
TI  - Minimizing health disparities among LGBT patients.

PMID- 25562249
TI  - Radiante: Olga Albizu.

PMID- 25562251
TI  - JAMA Forum: Lung cancer screening and evidence-based policy.

PMID- 25562259
TI  - The role of private payers in payment reform.

PMID- 25562260
TI  - New challenges for electronic health records: confidentiality and access to
      sensitive health information about parents and adolescents.

PMID- 25562261
TI  - Perspectives on cardiovascular screening.

PMID- 25562262
TI  - A piece of my mind. Skin deep.

PMID- 25562263
TI  - Mortality in type 1 diabetes in the current era: two steps forward, one step
      backward.

PMID- 25562264
TI  - Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010.
AB  - IMPORTANCE: Type 1 diabetes has historically been associated with a significant
      reduction in life expectancy. Major advances in treatment of type 1 diabetes have
      occurred in the past 3 decades. Contemporary estimates of the effect of type 1
      diabetes on life expectancy are needed. OBJECTIVE: To examine current life
      expectancy in people with and without type 1 diabetes in Scotland. We also
      examined whether any loss of life expectancy in patients with type 1 diabetes is
      confined to those who develop kidney disease. DESIGN, SETTING, AND PARTICIPANTS:
      Prospective cohort of all individuals alive in Scotland with type 1 diabetes who
      were aged 20 years or older from 2008 through 2010 and were in a nationwide
      register (n=24,691 contributing 67,712 person-years and 1043 deaths). MAIN
      OUTCOMES AND MEASURES: Differences in life expectancy between those with and
      those without type 1 diabetes and the percentage of the difference due to various
      causes. RESULTS: Life expectancy at an attained age of 20 years was an additional
      46.2 years among men with type 1 diabetes and 57.3 years among men without it, an
      estimated loss in life expectancy with diabetes of 11.1 years (95% CI, 10.1
      12.1). Life expectancy from age 20 years was an additional 48.1 years among women
      with type 1 diabetes and 61.0 years among women without it, an estimated loss
      with diabetes of 12.9 years (95% CI, 11.7-14.1). Even among those with type 1
      diabetes with an estimated glomerular filtration rate of 90 mL/min/1.73 m2 or
      higher, life expectancy was reduced (49.0 years in men, 53.1 years in women)
      giving an estimated loss from age 20 years of 8.3 years (95% CI, 6.5-10.1) for
      men and 7.9 years (95% CI, 5.5-10.3) for women. Overall, the largest percentage
      of the estimated loss in life expectancy was related to ischemic heart disease
      (36% in men, 31% in women) but death from diabetic coma or ketoacidosis was
      associated with the largest percentage of the estimated loss occurring before age
      50 years (29.4% in men, 21.7% in women). CONCLUSIONS AND RELEVANCE: Estimated
      life expectancy for patients with type 1 diabetes in Scotland based on data from
      2008 through 2010 indicated an estimated loss of life expectancy at age 20 years
      of approximately 11 years for men and 13 years for women compared with the
      general population without type 1 diabetes.

PMID- 25562265
TI  - Association between 7 years of intensive treatment of type 1 diabetes and long
      term mortality.
AB  - IMPORTANCE: Whether mortality in type 1 diabetes mellitus is affected following
      intensive glycemic therapy has not been established. OBJECTIVE: To determine
      whether mortality differed between the original intensive and conventional
      treatment groups in the long-term follow-up of the Diabetes Control and
      Complications Trial (DCCT) cohort. DESIGN, SETTING, AND PARTICIPANTS: After the
      DCCT (1983-1993) ended, participants were followed up in a multisite (27 US and
      Canadian academic clinical centers) observational study (Epidemiology of Diabetes
      Control and Complications [EDIC]) until December 31, 2012. Participants were 1441
      healthy volunteers with diabetes mellitus who, at baseline, were 13 to 39 years
      of age with 1 to 15 years of diabetes duration and no or early microvascular
      complications, and without hypertension, preexisting cardiovascular disease, or
      other potentially life-threatening disease. INTERVENTIONS AND EXPOSURES: During
      the clinical trial, participants were randomly assigned to receive intensive
      therapy (n = 711) aimed at achieving glycemia as close to the nondiabetic range
      as safely possible, or conventional therapy (n = 730) with the goal of avoiding
      symptomatic hypoglycemia and hyperglycemia. At the end of the DCCT, after a mean
      of 6.5 years, intensive therapy was taught and recommended to all participants
      and diabetes care was returned to personal physicians. MAIN OUTCOMES AND
      MEASURES: Total and cause-specific mortality was assessed through annual contact
      with family and friends and through records over 27 years' mean follow-up.
      RESULTS: Vital status was ascertained for 1429 (99.2%) participants. There were
      107 deaths, 64 in the conventional and 43 in the intensive group. The absolute
      risk difference was -109 per 100,000 patient-years (95% CI, -218 to -1), with
      lower all-cause mortality risk in the intensive therapy group (hazard ratio [HR]
      = 0.67 [95% CI, 0.46-0.99]; P = .045). Primary causes of death were
      cardiovascular disease (24 deaths; 22.4%), cancer (21 deaths; 19.6%), acute
      diabetes complications (19 deaths; 17.8%), and accidents or suicide (18 deaths;
      16.8%). Higher levels of glycated hemoglobin (HbA1c) were associated with all
      cause mortality (HR = 1.56 [95% CI, 1.35-1.81 per 10% relative increase in
      HbA1c]; P < .001), as well as the development of albuminuria (HR = 2.20 [95% CI,
      1.46-3.31]; P < .001). CONCLUSIONS AND RELEVANCE: After a mean of 27 years'
      follow-up of patients with type 1 diabetes, 6.5 years of initial intensive
      diabetes therapy was associated with a modestly lower all-cause mortality rate
      when compared with conventional therapy. TRIAL REGISTRATION: clinicaltrials.gov
      Identifiers: NCT00360815 and NCT00360893.

PMID- 25562266
TI  - Quadrivalent HPV vaccination and risk of multiple sclerosis and other
      demyelinating diseases of the central nervous system.
AB  - IMPORTANCE: Case reports have suggested a link between human papillomavirus (HPV)
      vaccination and development of multiple sclerosis and other demyelinating
      diseases. OBJECTIVE: To investigate if quadrivalent HPV (qHPV) vaccination is
      associated with an increased risk of multiple sclerosis and other demyelinating
      diseases. DESIGN, SETTING, AND PARTICIPANTS: Using nationwide registers we
      identified a cohort of all females aged 10 years to 44 years in Denmark and
      Sweden, followed up from 2006 to 2013, information on qHPV vaccination, and data
      on incident diagnoses of multiple sclerosis and other demyelinating diseases. The
      primary analysis used a cohort design including vaccinated and unvaccinated study
      participants. A secondary analysis used a self-controlled case-series design
      including only cases. Both analyses used a 2-year risk period following
      vaccination. EXPOSURES: Information on qHPV vaccination was obtained through the
      national vaccination and prescription registers. MAIN OUTCOMES AND MEASURES: The
      primary outcomes were multiple sclerosis and a composite end point of other
      demyelinating diseases. Incidence rate ratios were estimated using Poisson
      regression, comparing rates of events in the 2-year risk periods following
      vaccination and in unvaccinated time periods. RESULTS: The study included
      3,983,824 females, among whom 789,082 received a total of 1,927,581 qHPV vaccine
      doses. During follow-up, 4322 multiple sclerosis cases and 3300 cases of other
      demyelinating diseases were identified, of which 73 and 90, respectively,
      occurred within the risk period. In the cohort analysis, there was no increased
      risk of multiple sclerosis (crude incidence rates, 6.12 events/100,000 person
      years [95% CI, 4.86-7.69] and 21.54 events/100,000 person-years [95% CI, 20.90
      22.20] for the vaccinated and unvaccinated periods; adjusted rate ratio, 0.90
      [95% CI, 0.70-1.15]) or other demyelinating diseases (crude incidence rates, 7.54
      events/100,000 person-years [95% CI, 6.13-9.27] and 16.14 events/100,000 person
      years [95% CI, 15.58-16.71]; adjusted rate ratio, 1.00 [95% CI, 0.80-1.26])
      associated with qHPV vaccination. Similarly, no increased risk was found using
      the self-controlled case-series design (multiple sclerosis: incidence ratio, 1.05
      [95% CI, 0.79-1.38]; other demyelinating diseases: incidence ratio, 1.14 [95% CI,
      0.88-1.47]). CONCLUSIONS AND RELEVANCE: In this study with nationwide coverage of
      2 Scandinavian countries, qHPV vaccination was not associated with the
      development of multiple sclerosis or other demyelinating diseases. These findings
      do not support concerns about a causal relationship between qHPV vaccination and
      demyelinating diseases.

PMID- 25562268
TI  - Traveler's diarrhea: a clinical review.
AB  - IMPORTANCE: Acute diarrhea is the most common illness that affects travelers to
      low-income regions of the world. Although improved hygiene has reduced the risk
      of traveler's diarrhea in many destinations, the risk remains high in others.
      OBJECTIVE: To review the current state of knowledge on the etiology, risk
      factors, prevention, and management of traveler's diarrhea. EVIDENCE REVIEW: A
      search of the PubMed, Google Scholar, and Cochrane Library databases for the
      period 2012-April 2014 was performed for articles on traveler's diarrhea. The
      database search yielded 2976 articles, of which 37 were included in this review.
      These were added to 85 articles previously identified by the authors. FINDINGS:
      Improved hygiene has reduced the risk of traveler's diarrhea from 20% or more
      (for a 2-week stay) to between 8% and 20% in some parts of the world. Acquiring
      traveler's diarrhea causes 12% to 46% of travelers to change their travel plans.
      Returning travelers seeking medical care have a diagnosis of gastrointestinal
      disturbance in approximately one-third of all cases. Postinfectious irritable
      bowel syndrome may occur in 3% to 17% of patients who have had traveler's
      diarrhea. Prevention of traveler's diarrhea by dietary avoidance measures is
      often not successful. Chemoprophylaxis should be restricted to travelers who are
      at risk of severe complications of diarrhea. Ciprofloxacin is the standard
      treatment in self-therapy of traveler's diarrhea except when patients are in
      South or Southeast Asia, where azithromycin is preferred. CONCLUSIONS AND
      RELEVANCE: Diarrhea remains a common problem for international travelers. Persons
      intending to travel to at-risk countries should be counseled regarding prevention
      measures and may be given a travel pack that includes medications for self
      treatment should they become ill.

PMID- 25562269
TI  - Maternal mental health after a child's diagnosis of autism spectrum disorder.

PMID- 25562267
TI  - Association between bariatric surgery and long-term survival.
AB  - IMPORTANCE: Accumulating evidence suggests that bariatric surgery improves
      survival among patients with severe obesity, but research among veterans has
      shown no evidence of benefit. OBJECTIVE: To examine long-term survival in a large
      multisite cohort of patients who underwent bariatric surgery compared with
      matched control patients. DESIGN, SETTING, AND PARTICIPANTS: In a retrospective
      cohort study, we identified 2500 patients (74% men) who underwent bariatric
      surgery in Veterans Affairs (VA) bariatric centers from 2000-2011 and matched
      them to 7462 control patients using sequential stratification and an algorithm
      that included age, sex, geographic region, body mass index, diabetes, and
      Diagnostic Cost Group. Survival was compared across patients who underwent
      bariatric surgery and matched controls using Kaplan-Meier estimators and
      stratified, adjusted Cox regression analyses. EXPOSURES: Bariatric procedures,
      which included 74% gastric bypass, 15% sleeve gastrectomy, 10% adjustable gastric
      banding, and 1% other. MAIN OUTCOMES AND MEASURES: All-cause mortality through
      December 2013. RESULTS: Surgical patients (n = 2500) had a mean age of 52 years
      and a mean BMI of 47. Matched control patients (n = 7462) had a mean age of 53
      years and a mean BMI of 46. At the end of the 14-year study period, there were a
      total of 263 deaths in the surgical group (mean follow-up, 6.9 years) and 1277
      deaths in the matched control group (mean follow-up, 6.6 years). Kaplan-Meier
      estimated mortality rates were 2.4% at 1 year, 6.4% at 5 years, and 13.8% at 10
      years for surgical patients; for matched control patients, 1.7% at 1 year, 10.4%
      at 5 years, and 23.9% at 10 years. Adjusted analysis showed no significant
      association between bariatric surgery and all-cause mortality in the first year
      of follow-up (adjusted hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]), but
      significantly lower mortality after 1 to 5 years (HR, 0.45 [95% CI, 0.36-0.56])
      and 5 to 14 years (HR, 0.47 [95% CI, 0.39-0.58]). The midterm (>1-5 years) and
      long-term (>5 years) relationships between surgery and survival were not
      significantly different across subgroups defined by diabetes diagnosis, sex, and
      period of surgery. CONCLUSIONS AND RELEVANCE: Among obese patients receiving care
      in the VA health system, those who underwent bariatric surgery compared with
      matched control patients who did not have surgery had lower all-cause mortality
      at 5 years and up to 10 years following the procedure. These results provide
      further evidence for the beneficial relationship between surgery and survival
      that has been demonstrated in younger, predominantly female populations.

PMID- 25562270
TI  - A 38-year-old man with extensor surface papules.

PMID- 25562271
TI  - An abnormal audiogram.

PMID- 25562272
TI  - Safety of assisted reproductive technology in the United States, 2000-2011.

PMID- 25562273
TI  - Management of patients with sickle cell disease.

PMID- 25562274
TI  - Management of patients with sickle cell disease.

PMID- 25562275
TI  - Management of patients with sickle cell disease--reply.

PMID- 25562276
TI  - Reanalyses of trial results.

PMID- 25562278
TI  - Reanalyses of trial results--reply.

PMID- 25562277
TI  - Risk profile of clinical trial participants.

PMID- 25562279
TI  - Risk profile of clinical trial participants--reply.

PMID- 25562283
TI  - Science and humanity.

PMID- 25562284
TI  - JAMA patient page. Traveler's diarrhea.

PMID- 25562285
TI  - Observation of the intrinsic bandgap behaviour in as-grown epitaxial twisted
      graphene.
AB  - Twisted graphene is of particular interest due to several intriguing
      characteristics, such as its the Fermi velocity, van Hove singularities and
      electronic localization. Theoretical studies recently suggested the possible
      bandgap opening and tuning. Here, we report a novel approach to producing
      epitaxial twisted graphene on SiC (0001) and the observation of its intrinsic
      bandgap behaviour. The direct deposition of C60 on pre-grown graphene layers
      results in few-layer twisted graphene confirmed by angular resolved photoemission
      spectroscopy and Raman analysis. The strong enhanced G band in Raman and sp(3)
      bonding characteristic in X-ray photoemission spectroscopy suggests the existence
      of interlayer interaction between adjacent graphene layers. The interlayer
      spacing between graphene layers measured by transmission electron microscopy is
      0.352 +/- 0.012 nm. Thermal activation behaviour and nonlinear current-voltage
      characteristics conclude that an intrinsic bandgap is opened in twisted graphene.
      Low sheet resistance (~ 160 Omega ?(-1) at 10 K) and high mobility (~2,000 cm(2)
      V(-1) s(-1) at 10 K) are observed.

PMID- 25562287
TI  - Sub-10 nm rutile titanium dioxide nanoparticles for efficient visible-light
      driven photocatalytic hydrogen production.
AB  - Titanium dioxide is a promising photocatalyst for water splitting, but it suffers
      from low visible light activity due to its wide band gap. Doping can narrow the
      band gap of titanium dioxide; however, new charge-carrier recombination centres
      may be introduced. Here we report the design of sub-10 nm rutile titanium dioxide
      nanoparticles, with an increased amount of surface/sub-surface defects to
      overcome the negative effects from bulk defects. Abundant defects can not only
      shift the top of the valence band of rutile titanium dioxide upwards for band-gap
      narrowing but also promote charge-carrier separation. The role of titanium(III)
      is to enhance, rather than initiate, the visible-light-driven water splitting.
      The sub-10 nm rutile nanoparticles exhibit the state-of-the-art activity among
      titanium dioxide-based semiconductors for visible-light-driven water splitting
      and the concept of ultra-small nanoparticles with abundant defects may be
      extended to the design of other robust semiconductor photocatalysts.

PMID- 25562288
TI  - Brief mindfulness induction could reduce aggression after depletion.
AB  - Many experiments have shown that one's ability to refrain from acting on
      aggressive impulses is likely to decrease following a prior act of self-control.
      This temporary state of self-control failure is known as ego-depletion. Although
      mindfulness is increasingly used to treat and manage aggressive behaviour, the
      extent to which mindfulness may counteract the depletion effect on aggression is
      yet to be determined. This study (N=110) investigated the effect of a laboratory
      induced one-time mindfulness meditation session on aggression following
      depletion. Aggression was assessed by the intensity of aversive noise blast
      participants delivered to an opponent on a computerised task. Depleted
      participants who received mindfulness induction behaved less aggressively than
      depleted participants with no mindfulness induction. Mindfulness also improved
      performance on a second measure of self-control (i.e., handgrip perseverance);
      however, this effect was independent of depletion condition. Motivational factors
      may help explain the dynamics of mindfulness, self-control, and aggression. 

PMID- 25562286
TI  - Antibiotics in ingested human blood affect the mosquito microbiota and capacity
      to transmit malaria.
AB  - Malaria reduction is most efficiently achieved by vector control whereby human
      populations at high risk of contracting and transmitting the disease are
      protected from mosquito bites. Here, we identify the presence of antibiotics in
      the blood of malaria-infected people as a new risk of increasing disease
      transmission. We show that antibiotics in ingested blood enhance the
      susceptibility of Anopheles gambiae mosquitoes to malaria infection by disturbing
      their gut microbiota. This effect is confirmed in a semi-natural setting by
      feeding mosquitoes with blood of children naturally infected with Plasmodium
      falciparum. Antibiotic exposure additionally increases mosquito survival and
      fecundity, which are known to augment vectorial capacity. These findings suggest
      that malaria transmission may be exacerbated in areas of high antibiotic usage,
      and that regions targeted by mass drug administration programs against
      communicable diseases may necessitate increased vector control. 

PMID- 25562289
TI  - Alternative synthesis of CuFeSe2 nanocrystals with magnetic and photoelectric
      properties.
AB  - Monodisperse CuFeSe2 nanocrystals of high quality have been successfully
      synthesized for the first time using a hot-solution injection method from the
      reaction of metallic acetylacetonates with diphenyl diselenide (Ph2Se2) in
      oleylamine with addition of oleic acid at 255  degrees C for 90 min. The
      characterizations of X-ray diffraction, electron microscopy, and compositional
      analysis reveal that the resulting CuFeSe2 nanocrystals are of tetragonal phase
      with a stoichiometric composition. The CuFeSe2 nanocrystals exhibit well-defined
      quasi-cubic shape with an average size of ~18 nm, and their shape can be tuned
      from quasi-cubes to quasi-spheres by adjusting the reaction parameters. Magnetic
      measurement reveals that the as-synthesized CuFeSe2 nanocrystals are
      ferromagnetic and paramagnetic at 4 and 300 K, respectively. Additionally, the
      current-voltage (I-V) behavior of the CuFeSe2 nanocrystals suggests that they are
      promising candidates for application in optoelectronics and solar energy
      conversion. 

PMID- 25562291
TI  - Fun and play in invertebrates.

PMID- 25562290
TI  - The biology of fun and the fun of biology.

PMID- 25562292
TI  - Playfulness and creativity.

PMID- 25562293
TI  - Do birds have the capacity for fun?

PMID- 25562294
TI  - The what as well as the why of animal fun.
AB  - Fun is functional: play is evolution's way of making sure animals acquire and
      perfect valuable skills in circumstances of relative safety. Yet precisely what
      animals find fun has seldom been examined for what it can potentially reveal
      about how they represent and think about the world. 

PMID- 25562295
TI  - Teasing and clowning in infancy.

PMID- 25562296
TI  - Play in the Peter Pan ape.

PMID- 25562297
TI  - Religion: more money, more morals.
AB  - Between 500 BCE and 300 BCE, religions worldwide underwent a dramatic shift,
      emphasizing morality and asceticism for the first time. A new study suggests that
      the emergence of this new type of religion can be explained by increases in
      prosperity. 

PMID- 25562298
TI  - Neurobiology: all synapses are created equal.
AB  - There are two main modalities of communication between neurons, known as
      electrical and chemical synaptic transmission. Despite striking differences in
      their underlying mechanisms, new evidence suggests that the formation of
      electrically and chemically mediated synapses is under common regulatory
      processes. 

PMID- 25562299
TI  - Playful fun in dogs.

PMID- 25562300
TI  - Linguistics: evolution and language change.
AB  - Linguists have long identified sound changes that occur in parallel. Now novel
      research shows how Bayesian modeling can capture complex concerted changes,
      revealing how evolution of sounds proceeds. 

PMID- 25562301
TI  - Epithelial cell division: Aurora kicks Lgl to the cytoplasmic curb.
AB  - The Drosophila neoplastic tumor suppressor Lethal giant larvae (Lgl) regulates
      apico-basal polarity in epithelia as well as the asymmetric segregation of cell
      fate in neural progenitors. Two new studies uncover a new facet of its regulation
      in epithelia, where Aurora-dependent phosphorylation triggers Lgl dissociation
      from the basolateral cortex to facilitate planar orientation of the mitotic
      spindle. 

PMID- 25562302
TI  - DNA damage responses: beyond double-strand break repair.
AB  - The RAG endonuclease generates DNA double strand breaks during antigen receptor
      gene assembly, an essential process for B- and T-lymphocyte development. However,
      a recent study reveals that RAG endonuclease activity affects natural killer cell
      function, demonstrating that such double strand breaks, and the responses they
      elicit, may have broad cellular effects. 

PMID- 25562303
TI  - Cognitive development: the neurocognitive basis of early prosociality.
AB  - Recent work has demonstrated that young children already engage in a variety of
      prosocial actions and evaluate the prosociality of others' behavior. A new study
      highlights the neural mechanisms that subserve perception and production of
      prosocial behavior in preschool children. 

PMID- 25562304
TI  - Sleep: the sound of a local alarm clock.
AB  - Besides the master clock located in the suprachiasmatic nucleus (SCN) of the
      brain, additional clocks are distributed across the central nervous system and
      the body. The role of these 'secondary' clocks remains unclear. A new study shows
      that the lack of an internal clock in histamine neurons profoundly perturbs
      sleep. 

PMID- 25562305
TI  - Play in dolphins.

PMID- 25562306
TI  - Play in fishes, frogs and reptiles.

PMID- 25562307
TI  - Polar stacking of molecules in liquid chloroform.
AB  - Using neutron diffraction and the isotopic substitution technique we have
      investigated the local structure of liquid chloroform. A strong tendency for
      polar stacking of molecules with collinear alignment of dipole moments is found.
      We speculate that these polar stacks contribute to the performance of chloroform
      as a solvent. 

PMID- 25562308
TI  - Linear trinuclear cobalt(II) single molecule magnet.
AB  - The introduction of NaBPh(4) into a methanolic solution of CoCl(2).(6)H(2)O and 2
      [(pyridine-2-ylimine)-methyl]phenol (Hpymp) afforded
      {[Co(II)(3)(pymp)(4)(MeOH)(2)][BPh(4)](2)}.(2)MeOH (1) with a centro
      symmetrically linear trinuclear structure. Magnetic analysis of 1 exhibited
      significant intracluster ferromagnetic exchange (2.4 cm(-1)) and slow relaxation
      of magnetization in both zero and non-zero static fields below 5 K, giving the
      first [Co(II)(3)] single molecule magnet with an effective energy barrier of
      17.2(3) cm(-1) under a 500 Oe dc field.

PMID- 25562309
TI  - A supramolecular ladder polymer prepared by hydrogen bonding-mediated self
      assembly of a metallomacrocycle.
AB  - A defect-free supramolecular ladder polymer was prepared by H-bond-mediated self
      assembly of a metallocycle 1 as determined by NMR, viscometry and dynamic laser
      light scattering studies. This ladder polymer further self-assembled into thicker
      bundles which subsequently folded into uniform-sized spheres in the solid state.

PMID- 25562310
TI  - Magnolol reduces UVB-induced photodamage by regulating matrix metalloproteinase
      activity.
AB  - In this study, we evaluated the anti-photoaging activity of magnolol in UV
      irradiated hairless mice, and hypothesized that magnolol would prevent photoaging
      in these animals. The inhibitory effect of magnolol on wrinkle formation was
      determined by analyzing the skin replica, histologically examining the epidermal
      thickness, and identifying damage to the collagen fibers. The protective effects
      of magnolol on UVB-induced skin photoaging were examined by determining the level
      of MMPs and mitogen-activated protein kinases (MAPKs). Exposure to UVB radiation
      significantly increased skin thickness and wrinkle grade, but magnolol treatment
      significantly reduced the average length and depth of wrinkles, and this was
      correlated with the inhibition of collagen fiber loss. The magnolol-treated group
      had remarkably decreased activity levels of MMP-1, -9, and -13 compared to the
      corresponding levels in the vehicle-treated UVB-irradiated group. These results
      indicate that magnolol prevents skin photoaging in UVB-irradiated hairless mice. 

PMID- 25562311
TI  - Inequities in health care utilization by people aged 50+: evidence from 12
      European countries.
AB  - The aim of this study is to describe the magnitude of educational inequities in
      the use of health care services, by people aged 50+, in 12 European countries,
      controlling for country-level heterogeneity. We consider four services: having
      seen or talked to 1) a general practitioner (GP) or 2) specialist, 3) having been
      hospitalized, and 4) having visited a dentist (only for prevention). Data derived
      from the SHARE (Survey of Health, Ageing and Retirement in Europe) project, a
      cross-national panel that collects information from individuals aged 50 and over.
      A Fixed Effects approach is applied, which is a valuable alternative to the
      application of conventional multilevel models in country-comparative analysis.
      The main findings of this study confirm that there is substantial educational
      inequity in the use of health care, although relevant differences arise between
      services. A clear pro-educated gradient is found for specialists and dentist
      visits, whereas no evidence of educational disparities was found for GP use. On
      the other hand, less clear results emerge regarding hospitalizations. However,
      the analysis shows that micro-level dimensions, i.e. individual needs and
      predisposing and enabling population characteristics, and macro level factors,
      i.e. health care system and welfare regime, interact to determine people's use of
      health services. It can be concluded that people with more education level have
      more resources (cognitive, communicative, relational) that allow them to make
      more informed choices and take more effective actions for their health goals,
      however, the institutional context may modify this relationship. 

PMID- 25562312
TI  - Racial resentment and smoking.
AB  - Racial resentment (also known as symbolic racism) is among the most widely tested
      measures of contemporary prejudice in political science and social psychological
      research over the past thirty years. Proponents argue that racial resentment
      reflects anti-black emotion obtained through pre-adult socialization. In light of
      affect-based models of substance use, this paper examined the association between
      racial resentment and smoking in a national sample of non-Hispanic white, black,
      and Hispanic respondents. Data come from the 2012 American National Election
      Study, which contained two measures of smoking. The results of ordinal logistic
      regression models indicate a positive association between racial resentment and
      smoking among non-Hispanic whites (N = 2133) that is not present among blacks (N
      = 693) or Hispanics (N = 660). Models controlled for age, education, income,
      gender, political ideology, region, and mode of interview. Furthermore, analyses
      indicated that a measure of race-related affect, admiration and sympathy towards
      blacks, partially mediated the association between racial resentment and smoking.
      For non-Hispanic whites, racial resentment appears to constitute a risk factor
      for smoking. Future studies should further specify the conditions linking
      substance use to the race-related affective component of racial resentment. 

PMID- 25562313
TI  - Polyethylenimine-grafted cellulose nanofibril aerogels as versatile vehicles for
      drug delivery.
AB  - Aerogels from polyethylenimine-grafted cellulose nanofibrils (CNFs-PEI) were
      developed for the first time as a novel drug delivery system. The morphology and
      structure of the CNFs before and after chemical modification were characterized
      by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy
      (FTIR), and X-ray photoelectron spectroscopy (XPS). Water-soluble sodium
      salicylate (NaSA) was used as a model drug for the investigation of drug loading
      and release performance. The CNFs-PEI aerogels exhibited a high drug loading
      capability (287.39 mg/g), and the drug adsorption process could be well described
      by Langmuir isotherm and pseudo-second-order kinetics models. Drug release
      experiments demonstrated a sustained and controlled release behavior of the
      aerogels highly dependent on pH and temperature. This process followed quite well
      the pseudo-second-order release kinetics. Owing to the unique pH- and temperature
      responsiveness together with their excellent biodegradability and
      biocompatibility, the CNFs-PEI aerogels were very promising as a new generation
      of controlled drug delivery carriers, offering simple and safe alternatives to
      the conventional systems from synthetic polymers. 

PMID- 25562314
TI  - A critical evaluation of current social neuroscience knowledge and new directions
      in understanding social behavior.

PMID- 25562315
TI  - Negative dielectrophoretic capture and repulsion of single cells at a bipolar
      electrode: the impact of faradaic ion enrichment and depletion.
AB  - This paper describes the dielectrophoretic (DEP) forces generated by a bipolar
      electrode (BPE) in a microfluidic device and elucidates the impact of faradaic
      ion enrichment and depletion (FIE and FID) on electric field gradients. DEP
      technologies for manipulating biological cells provide several distinct
      advantages over other cell-handling techniques including label-free selectivity,
      inexpensive device components, and amenability to single-cell and array-based
      applications. However, extension to the array format is nontrivial, and DEP
      forces are notoriously short-range, limiting device dimensions and throughput.
      BPEs present an attractive option for DEP because of the ease with which they can
      be arrayed. Here, we present experimental results demonstrating both negative DEP
      (nDEP) attraction and repulsion of B-cells from each a BPE cathode and anode. The
      direction of nDEP force in each case was determined by whether the conditions for
      FIE or FID were chosen in the experimental design. We conclude that FIE and FID
      zones generated by BPEs can be exploited to shape and extend the electric field
      gradients that are responsible for DEP force. 

PMID- 25562317
TI  - Association between respiratory syncytial virus activity and pneumococcal disease
      in infants: a time series analysis of US hospitalization data.
AB  - BACKGROUND: The importance of bacterial infections following respiratory
      syncytial virus (RSV) remains unclear. We evaluated whether variations in RSV
      epidemic timing and magnitude are associated with variations in pneumococcal
      disease epidemics and whether changes in pneumococcal disease following the
      introduction of seven-valent pneumococcal conjugate vaccine (PCV7) were
      associated with changes in the rate of hospitalizations coded as RSV. METHODS AND
      FINDINGS: We used data from the State Inpatient Databases (Agency for Healthcare
      Research and Quality), including >700,000 RSV hospitalizations and >16,000
      pneumococcal pneumonia hospitalizations in 36 states (1992/1993-2008/2009).
      Harmonic regression was used to estimate the timing of the average seasonal peak
      of RSV, pneumococcal pneumonia, and pneumococcal septicemia. We then estimated
      the association between the incidence of pneumococcal disease in children and the
      activity of RSV and influenza (where there is a well-established association)
      using Poisson regression models that controlled for shared seasonal variations.
      Finally, we estimated changes in the rate of hospitalizations coded as RSV
      following the introduction of PCV7. RSV and pneumococcal pneumonia shared a
      distinctive spatiotemporal pattern (correlation of peak timing: rho = 0.70, 95%
      CI: 0.45, 0.84). RSV was associated with a significant increase in the incidence
      of pneumococcal pneumonia in children aged <1 y (attributable percent [AP]:
      20.3%, 95% CI: 17.4%, 25.1%) and among children aged 1-2 y (AP: 10.1%, 95% CI:
      7.6%, 13.9%). Influenza was also associated with an increase in pneumococcal
      pneumonia among children aged 1-2 y (AP: 3.2%, 95% CI: 1.7%, 4.7%). Finally, we
      observed a significant decline in RSV-coded hospitalizations in children aged <1
      y following PCV7 introduction (-18.0%, 95% CI: -22.6%, -13.1%, for 2004/2005
      2008/2009 versus 1997/1998-1999/2000). This study used aggregated hospitalization
      data, and studies with individual-level, laboratory-confirmed data could help to
      confirm these findings. CONCLUSIONS: These analyses provide evidence for an
      interaction between RSV and pneumococcal pneumonia. Future work should evaluate
      whether treatment for secondary bacterial infections could be considered for
      pneumonia cases even if a child tests positive for RSV. Please see later in the
      article for the Editors' Summary.

PMID- 25562316
TI  - Finding our way through phenotypes.
AB  - Despite a large and multifaceted effort to understand the vast landscape of
      phenotypic data, their current form inhibits productive data analysis. The lack
      of a community-wide, consensus-based, human- and machine-interpretable language
      for describing phenotypes and their genomic and environmental contexts is perhaps
      the most pressing scientific bottleneck to integration across many key fields in
      biology, including genomics, systems biology, development, medicine, evolution,
      ecology, and systematics. Here we survey the current phenomics landscape,
      including data resources and handling, and the progress that has been made to
      accurately capture relevant data descriptions for phenotypes. We present an
      example of the kind of integration across domains that computable phenotypes
      would enable, and we call upon the broader biology community, publishers, and
      relevant funding agencies to support efforts to surmount today's data barriers
      and facilitate analytical reproducibility. 

PMID- 25562318
TI  - Vascular adhesion protein-1 promotes liver inflammation and drives hepatic
      fibrosis.
AB  - Nonalcoholic fatty liver disease (NAFLD) encompasses a range of manifestations,
      including steatosis and cirrhosis. Progressive disease is characterized by
      hepatic leukocyte accumulation in the form of steatohepatitis. The adhesion
      molecule vascular adhesion protein-1 (VAP-1) is a membrane-bound amine oxidase
      that promotes leukocyte recruitment to the liver, and the soluble form (sVAP-1)
      accounts for most circulating monoamine oxidase activity, has insulin-like
      effects, and can initiate oxidative stress. Here, we determined that hepatic VAP
      1 expression is increased in patients with chronic liver disease and that serum
      sVAP-1 levels are elevated in patients with NAFLD compared with those in control
      individuals. In 4 murine hepatic injury models, an absence or blockade of
      functional VAP-1 reduced inflammatory cell recruitment to the liver and
      attenuated fibrosis. Moreover, disease was reduced in animals expressing a
      catalytically inactive form of VAP-1, implicating enzyme activity in the disease
      pathogenesis. Within the liver, hepatic stromal cells expressed functional VAP-1,
      and evaluation of cultured cells revealed that sVAP-1 promotes leukocyte
      migration through catalytic generation of ROS, which depended on VAP-1 enzyme
      activity. VAP-1 enhanced stromal cell spreading and wound closure and modulated
      expression of profibrotic genes. Together, these results link the amine oxidase
      activity of VAP-1 with hepatic inflammation and fibrosis and suggest that
      targeting VAP-1 has therapeutic potential for NAFLD and other chronic fibrotic
      liver diseases. 

PMID- 25562319
TI  - PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis.
AB  - Although aging is a known risk factor for idiopathic pulmonary fibrosis (IPF),
      the pathogenic mechanisms that underlie the effects of advancing age remain
      largely unexplained. Some age-related neurodegenerative diseases have an etiology
      that is related to mitochondrial dysfunction. Here, we found that alveolar type
      II cells (AECIIs) in the lungs of IPF patients exhibit marked accumulation of
      dysmorphic and dysfunctional mitochondria. These mitochondrial abnormalities in
      AECIIs of IPF lungs were associated with upregulation of ER stress markers and
      were recapitulated in normal mice with advancing age in response to stimulation
      of ER stress. We found that impaired mitochondria in IPF and aging lungs were
      associated with low expression of PTEN-induced putative kinase 1 (PINK1).
      Knockdown of PINK1 expression in lung epithelial cells resulted in mitochondria
      depolarization and expression of profibrotic factors. Moreover, young PINK1
      deficient mice developed similarly dysmorphic, dysfunctional mitochondria in the
      AECIIs and were vulnerable to apoptosis and development of lung fibrosis. Our
      data indicate that PINK1 deficiency results in swollen, dysfunctional
      mitochondria and defective mitophagy, and promotes fibrosis in the aging lung. 

PMID- 25562320
TI  - Annexin1 regulates DC efferocytosis and cross-presentation during Mycobacterium
      tuberculosis infection.
AB  - The phagocytosis of apoptotic cells and associated vesicles (efferocytosis) by
      DCs is an important mechanism for both self tolerance and host defense. Although
      some of the engulfment ligands involved in efferocytosis have been identified and
      studied in vitro, the contributions of these ligands in vivo remain ill defined.
      Here, we determined that during Mycobacterium tuberculosis (Mtb) infection, the
      engulfment ligand annexin1 is an important mediator in DC cross-presentation that
      increases efferocytosis in DCs and intrinsically enhances the capacity of the DC
      antigen-presenting machinery. Annexin1-deficient mice were highly susceptible to
      Mtb infection and showed an impaired Mtb antigen-specific CD8+ T cell response.
      Importantly, annexin1 expression was greatly downregulated in Mtb-infected human
      blood monocyte-derived DCs, indicating that reduction of annexin1 is a critical
      mechanism for immune evasion by Mtb. Collectively, these data indicate that
      annexin1 is essential in immunity to Mtb infection and mediates the power of DC
      efferocytosis and cross-presentation. 

PMID- 25562321
TI  - Telomerase mutations in smokers with severe emphysema.
AB  - Mutations in the essential telomerase genes TERT and TR cause familial pulmonary
      fibrosis; however, in telomerase-null mice, short telomeres predispose to
      emphysema after chronic cigarette smoke exposure. Here, we tested whether
      telomerase mutations are a risk factor for human emphysema by examining their
      frequency in smokers with chronic obstructive pulmonary disease (COPD). Across
      two independent cohorts, we found 3 of 292 severe COPD cases carried deleterious
      mutations in TERT (1%). This prevalence is comparable to the frequency of alpha-1
      antitrypsin deficiency documented in this population. The TERT mutations
      compromised telomerase catalytic activity, and mutation carriers had short
      telomeres. Telomerase mutation carriers with emphysema were predominantly female
      and had an increased incidence of pneumothorax. In families, emphysema showed an
      autosomal dominant inheritance pattern, along with pulmonary fibrosis and other
      telomere syndrome features, but manifested only in smokers. Our findings identify
      germline mutations in telomerase as a Mendelian risk factor for COPD
      susceptibility that clusters in autosomal dominant families with telomere
      mediated disease including pulmonary fibrosis. 

PMID- 25562323
TI  - Increased glutamine catabolism mediates bone anabolism in response to WNT
      signaling.
AB  - WNT signaling stimulates bone formation by increasing both the number of
      osteoblasts and their protein-synthesis activity. It is not clear how WNT
      augments the capacity of osteoblast progenitors to meet the increased energetic
      and synthetic needs associated with mature osteoblasts. Here, in cultured
      osteoblast progenitors, we determined that WNT stimulates glutamine catabolism
      through the tricarboxylic acid (TCA) cycle and consequently lowers intracellular
      glutamine levels. The WNT-induced reduction of glutamine concentration triggered
      a general control nonderepressible 2-mediated (GCN2-mediated) integrated stress
      response (ISR) that stimulated expression of genes responsible for amino acid
      supply, transfer RNA (tRNA) aminoacylation, and protein folding. WNT-induced
      glutamine catabolism and ISR were beta-catenin independent, but required
      mammalian target of rapamycin complex 1 (mTORC1) activation. In a hyperactive WNT
      signaling mouse model of human osteosclerosis, inhibition of glutamine catabolism
      or Gcn2 deletion suppressed excessive bone formation. Together, our data indicate
      that glutamine is both an energy source and a protein-translation rheostat that
      is responsive to WNT and suggest that manipulation of the glutamine/GCN2
      signaling axis may provide a valuable approach for normalizing deranged protein
      anabolism associated with human diseases. 

PMID- 25562322
TI  - Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer
      patient prognosis.
AB  - The composition of tumor-targeted T cell infiltrates is a major prognostic factor
      in colorectal cancer (CRC) outcome; however, the functional role of these
      populations in prolonging patient survival remains unclear. Here, we evaluated
      190 patients with CRC for the presence of functionally active tumor-infiltrating
      lymphocytes (TILs), the tumor specificity of these TILs, and the correlation
      between patient TILs and long-term survival. Using intracytoplasmic cytokine
      staining in conjunction with HLA multimers loaded with tumor peptide and antigen
      specific cytokine secretion assays, we determined that TNF-alpha expression
      delineates a population of tumor antigen-specific (TA-specific) cytotoxic T
      lymphocytes (CTLs) present within tumors from patients with CRC. Upregulation of
      TNF-alpha expression in TILs strongly correlated with an increase in the total
      amount of intratumoral TNF-alpha, which is indicative of tumor-specific CTL
      activity. Moreover, a retrospective multivariate analysis of 102 patients with
      CRC, which had multiple immune parameters evaluated, revealed that increased TNF
      alpha concentration was an independent prognostic factor. Together, these results
      indicate that the prognostic impact of T cell infiltrates for CRC maybe largely
      based on subpopulations of active TA-specific T cells within the tumor,
      suggesting causal implication for these cells in patient survival. Additionally,
      these results support the use of intratumoral TNF-alpha, which is indicative of T
      cell function, as a prognostic parameter for CRC. 

PMID- 25562325
TI  - Three-dimensional CaP/gelatin lattice scaffolds with integrated osteoinductive
      surface topographies for bone tissue engineering.
AB  - Surface topography is known to influence stem cells and has been widely used as
      physical stimuli to modulate cellular behaviour including adhesion, proliferation
      and differentiation on 2D surfaces. Integration of well-defined surface
      topography into three-dimensional (3D) scaffolds for tissue engineering would be
      useful to direct the cell fate for intended applications. Technical challenges
      are remaining as how to fabricate such 3D scaffolds with controlled surface
      topography from a range of biodegradable and biocompatible materials. In this
      paper, a novel fabrication process using computer numerically controlled
      machining and lamination is reported to make 3D calcium phosphate/gelatin
      composite scaffolds with integrated surface micropatterns that are introduced by
      embossing prior to machining. Geometric analysis shows that this method is
      versatile and can be used to make a wide range of lattices with porosities that
      meet the basic requirements for bone tissue engineering. Both in vitro and in
      vivo studies show that micropatterned composite scaffolds with surfaces
      comprising 40 MUm pits and 50 MUm grooves were optimal for improved osteogenesis.
      The results have demonstrated the potential of a novel fabrication process for
      producing cell-instructive scaffolds with designed surface topographies to induce
      specific tissue regeneration. 

PMID- 25562326
TI  - Cooled semen for fixed-time artificial insemination in beef cattle.
AB  - This study evaluated the use of cooled semen in a fixed-time artificial
      insemination (FTAI) program compared with frozen-thawed semen to improve
      pregnancy rates in beef cattle. Ejaculates of three bulls were collected and
      divided into two treatments: (1) frozen-thawed semen and (2) cooled semen. Egg
      yolk extender without glycerol was used for the cooled semen treatment. Straws
      (25*106 spermatozoa) were submitted to cooling for preservation at 5 degrees C
      for 24h, after which FTAI was performed. Nelore cows (n=838) submitted to FTAI
      were randomly inseminated using frozen-thawed semen or cooled semen. There was a
      20% increase in the pregnancy per AI (P AI-1) using cooled semen compared with
      frozen-thawed semen (59.9+/-4.7 vs 49.4+/-5.0%; P<0.005). There was no difference
      in P AI-1 among the bulls (P=0.40). The frozen-thawed semen had fewer functional
      spermatozoa than did the cooled semen when evaluated by sperm motility (61.7 vs
      81.0%), slow thermoresistance test (41.7 vs 66.7%) and hypoosmotic swelling test
      (38.3 vs 53.7%; P<0.05). The percentage of sperm abnormalities did not differ
      between the freeze-thawing and cooling processes (18.6 vs 22.1%; P>0.05). Because
      there was less damage to spermatozoa and improvement in P AI-1, the use of cooled
      semen instead of frozen-thawed semen is an interesting approach to increase
      reproductive efficiency in cattle submitted to a FTAI protocol.

PMID- 25562327
TI  - Adipose-derived stem cells from both visceral and subcutaneous fat deposits
      significantly improve contractile function of infarcted rat hearts.
AB  - Adipose-derived stem cells (ASCs) from subcutaneous and visceral adipose tissues
      have been studied individually. No studies have compared their abilities in
      treatment of heart failure. This study was designed to evaluate whether ASCs from
      the two sources could provide a long-term improvement of cardiac function in
      infarcted hearts. Rat subcutaneous and visceral adipose tissues were excised for
      isolation of ASCs. Morphology, yield, proliferation, surface markers,
      differentiation, and cytokine secretion of the subcutaneous ASCs (S-ASCs) and
      visceral ASCs (V-ASCs) were analyzed. Then a rat model of myocardial infarction
      (MI) was established by a coronary occlusion. Seven days after occlusion, S-ASCs
      (n = 22), V-ASCs (n = 22), and Dulbecco's modified Eagle medium (DMEM, n = 20)
      were injected into the infarct rim, respectively. Cardiac function was then
      monitored with MRI for up to 6 months. The hearts were then removed for
      histological assessments. The yield of V-ASCs per gram of the visceral adipose
      depot was significantly greater than that of S-ASCs in 1 g of the subcutaneous
      adipose depot. On the other hand, the S-ASCs showed a greater proliferation rate
      and colony-forming unit relative to the V-ASCs. In addition, the infarcted hearts
      treated with either S-ASCs or V-ASCs showed a significantly greater left
      ventricular ejection fraction (LVEF) than those treated with DMEM at 4 weeks and
      6 months following the cell/DMEM transplantation. Moreover, the infarct sizes of
      both S-ASC- and V-ASC-treated hearts were significantly smaller than that in the
      DMEM-treated hearts. MRI showed the implanted ASCs at the end of 6 months of
      recovery. Despite the differences in cell yield, proliferation, and colony
      formation capacity, both S-ASCs and V-ASCs provide a long-lasting improvement of
      cardiac contractile function in infarcted hearts. We conclude that the
      subcutaneous and visceral adipose tissues are equally effective cell sources for
      cell therapy of heart failure. 

PMID- 25562328
TI  - Characterisation of several ankyrin repeat protein variant 2, a phosphoprotein
      phosphatase 1-interacting protein, in testis and spermatozoa.
AB  - Phosphoprotein phosphatase 1 (PPP1) catalytic subunit gamma 2 (PPP1CC2), a PPP1
      isoform, is largely restricted to testicular germ cells and spermatozoa. The key
      to understanding PPP1 regulation in male germ cells lies in the identification
      and characterisation of its interacting partners. This study was undertaken to
      determine the expression patterns of the several ankyrin repeat protein variant 2
      (SARP2), a PPP1-interacting protein, in testis and spermatozoa. SARP2 was found
      to be highly expressed in testis and spermatozoa, and its interaction with human
      spermatozoa endogenous PPP1CC2 was confirmed by immunoprecipitation. Expression
      analysis by RT-qPCR revealed that SARP2 and PPP1CC2 mRNA levels were
      significantly higher in the spermatocyte fraction. However, microscopy revealed
      that SARP2 protein was only present in the nucleus of elongating and mature
      spermatids and in spermatozoa. In spermatozoa, SARP2 was prominently expressed in
      the connecting piece and flagellum, as well as, to a lesser extent, in the
      acrosome. A yeast two-hybrid approach was used to detect SARP2-interacting
      proteins and a relevant interaction with a novel sperm-associated antigen 9
      (SPAG9) variant, a testis and spermatozoa-specific c-Jun N-terminal kinase
      binding protein, was validated in human spermatozoa. Given the expression pattern
      of SARP2 and its association with PPP1CC2 and SPAG9, it may play a role in
      spermiogenesis and sperm function, namely in sperm motility and the acrosome
      reaction.

PMID- 25562329
TI  - Fabrication of Au@Ag core/shell nanoparticles decorated TiO2 hollow structure for
      efficient light-harvesting in dye-sensitized solar cells.
AB  - Improving the light-harvesting properties of photoanodes is promising way to
      enhance the power conversion efficiency (PCE) of dye-sensitized solar cells
      (DSSCs). We synthesized Au@Ag core/shell nanoparticles decorated TiO2 hollow
      nanoparticles (Au@Ag/TiO2 HNPs) via sol-gel reaction and chemical deposition. The
      Au@Ag/TiO2 HNPs exhibited multifunctions from Au@Ag core/shell NPs (Au@Ag CSNPs)
      and TiO2 hollow nanoparticles (TiO2 HNPs). These Au@Ag CSNPs exhibited strong and
      broadened localized surface plasmon resonance (LSPR), together with a large
      specific surface area of 129 m(2) g(-1), light scattering effect, and facile
      oxidation-reduction reaction of electrolyte from TiO2 HNPs, which resulted in
      enhancement of the light harvesting. The optimum PCE of eta = 9.7% was achieved
      for the DSSCs using photoanode materials based on TiO2 HNPs containing Au@Ag/TiO2
      HNPs (0.2 wt % Au@Ag CSNPs with respect to TiO2 HNPs), which outperformed by 24%
      enhancement that of conventional photoanodes formed using P25 (eta = 7.8%). 

PMID- 25562331
TI  - Interleukin-27 and interleukin-23 in patients with systemic lupus erythematosus:
      possible role in lupus nephritis.
AB  - OBJECTIVES: To analyse the concentration of interleukin (IL)-27 and IL-23 in
      serum and urine of patients with systemic lupus erythematosus (SLE) compared with
      healthy controls (HC). METHOD: An enzyme-linked immunosorbent assay (ELISA) was
      used to analyse the serum and urine concentration of IL-27 and IL-23 from 50
      patients with lupus nephritis (LN), 55 patients without LN, and 30 HC. The
      correlations between the levels of IL-27, IL-23, and disease activity, clinical
      parameters in SLE patients were analysed. RESULTS: The levels of IL-27 and IL-23
      increased significantly in the serum and urine of SLE patients with and without
      LN compared with HC. Moreover, urine levels of IL-27 and IL-23 were correlated
      with the renal SLE Disease Activity Index (rSLEDAI) score and 24-h urinary
      protein levels. After 6 months of immunosuppressive treatment, urine IL-27
      expression rose significantly in SLE patients with LN. CONCLUSIONS: IL-27 and IL
      23 may be involved in the pathogenesis of LN.

PMID- 25562332
TI  - A mathematical theory of ability measure based on partial credit item responses.
AB  - This paper defines a measure of examinees' abilities using additivity, the
      fundamental property of a measure, based on the partially-credited item
      responses. The fundamental properties of this newly-defined ability measure are
      demonstrated using mathematical proofs. This paper also shows that interactive
      ability and conditional ability are measurable with additivity. Finally, the
      paper looks at the ability measures associated with subscales and their
      decompositions. 

PMID- 25562330
TI  - Sarcopenia Defined by Combining Height- and Weight-Adjusted Skeletal Muscle
      Indices is Closely Associated With Poor Physical Performance.
AB  - OBJECTIVES: To compare muscle strength and physical performance among subjects
      with and without sarcopenia of different definitions. DESIGN: A population-based
      cross-sectional study. PARTICIPANTS: 857 community residents aged 65 years or
      older. METHODS: Sarcopenia was defined according to the European Working Group of
      Sarcopenia in Older People consensus criteria. Dual-energy X-ray absorptiometry
      measured lean soft tissue mass. Sarcopenic participants with low height-adjusted
      or weight-adjusted skeletal muscle index (SMI) were classified as having h
      sarcopenia or w-sarcopenia, respectively. Combined sarcopenia (c-sarcopenia) was
      defined as having either h- or w-sarcopenia. The participants underwent six
      physical performance tests: walking speed, timed up-and-go, six-minute walk,
      single-leg stance, timed chair stands, and flexibility test. The strength of five
      muscle groups was measured. RESULTS: Participants with h-sarcopenia had lower
      weight, body mass index (BMI), fat mass, and absolute muscle strength (p <=
      .001); those with w-sarcopenia had higher weight, BMI, fat mass (p < .001), and
      low relative muscle strength (p <= .003). Participants with c-sarcopenia had
      poorer performance in all physical performance tests, whereas h-sarcopenia and w
      sarcopenia were associated with poor performance in four tests. CONCLUSION:
      Subjects with h- and w-sarcopenia differ significantly in terms of obesity
      indicators. Combining height- and weight-adjusted SMIs can be a feasible method
      to define sarcopenia.

PMID- 25562324
TI  - The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following
      necrosis.
AB  - In contrast to microbially triggered inflammation, mechanisms promoting sterile
      inflammation remain poorly understood. Damage-associated molecular patterns
      (DAMPs) are considered key inducers of sterile inflammation following cell death,
      but the relative contribution of specific DAMPs, including high-mobility group
      box 1 (HMGB1), is ill defined. Due to the postnatal lethality of Hmgb1-knockout
      mice, the role of HMGB1 in sterile inflammation and disease processes in vivo
      remains controversial. Here, using conditional ablation strategies, we have
      demonstrated that epithelial, but not bone marrow-derived, HMGB1 is required for
      sterile inflammation following injury. Epithelial HMGB1, through its receptor
      RAGE, triggered recruitment of neutrophils, but not macrophages, toward necrosis.
      In clinically relevant models of necrosis, HMGB1/RAGE-induced neutrophil
      recruitment mediated subsequent amplification of injury, depending on the
      presence of neutrophil elastase. Notably, hepatocyte-specific HMGB1 ablation
      resulted in 100% survival following lethal acetaminophen intoxication. In
      contrast to necrosis, HMGB1 ablation did not alter inflammation or mortality in
      response to TNF- or FAS-mediated apoptosis. In LPS-induced shock, in which HMGB1
      was considered a key mediator, HMGB1 ablation did not ameliorate inflammation or
      lethality, despite efficient reduction of HMGB1 serum levels. Our study
      establishes HMGB1 as a bona fide and targetable DAMP that selectively triggers a
      neutrophil-mediated injury amplification loop in the setting of necrosis. 

PMID- 25562333
TI  - Differential item functioning analysis by applying multiple comparison
      procedures.
AB  - Analysis within a Rasch measurement framework aims at development of valid and
      objective test score. One requirement of both validity and objectivity is that
      items do not show evidence of differential item functioning (DIF). A number of
      procedures exist for the assessment of DIF including those based on analysis of
      contingency tables by Mantel-Haenszel tests and partial gamma coefficients. The
      aim of this paper is to illustrate Multiple Comparison Procedures (MCP) for
      analysis of DIF relative to a variable defining a very large number of groups,
      with an unclear ordering with respect to the DIF effect. We propose a single step
      procedure controlling the false discovery rate for DIF detection. The procedure
      applies for both dichotomous and polytomous items. In addition to providing
      evidence against a hypothesis of no DIF, the procedure also provides information
      on subset of groups that are homogeneous with respect to the DIF effect. A
      stepwise MCP procedure for this purpose is also introduced. 

PMID- 25562334
TI  - Visually discriminating upper case letters, lower case letters and numbers.
AB  - English and number literacy are important for successful learning and testing
      student literacy and numeracy standards enables early identification and
      remediation of children who have difficulty. Rasch measures were created with the
      RUMM2020 computer program for the perceptual constructs of visual discrimination
      upper case letters, lower case letters and numbers. Thirty items for Visual
      Discrimination of Upper Case Letters (VDUCL), 36 for Lower Case Letters (VDLCL)
      and 20 for Visual Discrimination of Numbers (VDN) were presented to 324 Pre
      Primary through Year 4 children, aged 4-9 years old. All students attended school
      in Perth, Western Australia. Eighteen of the initial 30 items for VDUCL, thirty
      one of the original 36 items for VDLCL and thirteen of the original 20 items for
      VDN were used to create linear scales (the others were deleted due to misfit) and
      these clearly showed which letters and numbers children said were easy and which
      were hard. 

PMID- 25562335
TI  - Testing the multidimensionality of the inventory of school motivation in a Dutch
      student sample.
AB  - A factor analytic and a Rasch measurement approach were applied to evaluate the
      multidimensional nature of the school motivation construct among more than 7,000
      Dutch secondary school students. The Inventory of School Motivation (McInerney
      and Ali, 2006) was used, which intends to measure four motivation dimensions
      (mastery, performance, social, and extrinsic motivation), each comprising of two
      first-order factors. One unidimensional model and three multidimensional models
      (4-factor, 8-factor, higher order) were fit to the data. Results of both
      approaches showed that the multidimensional models validly represented the school
      motivation among Dutch secondary school pupils, whereas model fit of the
      unidimensional model was poor. The differences in model fit between the three
      multidimensional models were small, although a different model was favoured by
      the two approaches. The need for improvement of some of the items and the need to
      increase measurement precision of several first-order factors are discussed. 

PMID- 25562336
TI  - Measuring Teaching Assistants' Efficacy using the Rasch Model.
AB  - Teaching assistants (TAs) play an influential role in primary and secondary
      schools. But there is an absence in literature about the TA's efficacy, and to
      date no instrument is available for measuring TA's efficacy. The present study
      aims to develop and validate a scale (Teaching Assistant Efficacy Scale, TAES)
      for measuring TA's efficacy on identified capabilities. A total of 531 teaching
      assistants from Hong Kong schools participated in the survey. The
      multidimensional Rasch model was used to analyse the data. The results revealed
      that a 5-dimension structure of TA's efficacy was supported. The final 30-item
      version of TAES assesses TA's efficacy on learning support, teaching support,
      behaviour management, cooperation, and administrative support. The Rasch
      reliabilities for all five dimensions were around 0.90. The 6-category response
      structure worked well for the scale. Further research was recommended to validate
      and test the robustness of the TAES both in Hong Kong and elsewhere. 

PMID- 25562337
TI  - Detecting measurement disturbance effects: the graphical display of item
      characteristics.
AB  - Traditional identification of misfitting items in Rasch measurement models have
      interpreted the Infit and Outfit z standardized statistic. A more recent approach
      made possible by Winsteps is to specify "group = 0" in the control file and
      subsequently view the item characteristic curve for each item against the true
      probability curve. The graphical display reveals whether an item follows the true
      probability curve or deviates substantially, thus indicating measurement
      disturbance. Probability of item response and logit ability are easily copied
      into data vectors in R software then graphed. An example control file, output
      item data, and subsequent preparation of an overlay graph for misfit items are
      presented using Winsteps and R software. For comparison purposes the data are
      also analyzed using a multi-dimensional (MD) mapping procedure. 

PMID- 25562338
TI  - Criteria weighting with respect to institution's goals for faculty selection.
AB  - Employers frequently select an employee among numerous candidates. They have to
      evaluate these candidates by multiple criteria that raise the problem of how to
      determinate the relative importance of these criteria. Traditionally, when
      engaging a new employee, the employer will develop a set of criteria and their
      associate weightings according with its institution's goals. However, the weight
      setting also reflects the priority of goals. It is frequently ignored. That is to
      say, it is necessary to recheck whether the weighting set reflects the
      institution's goals' priority appropriately. In this research, we proposed a
      mechanism that gives the chance to review the criteria weighting to see if it is
      adequately satisfies its institution's actual goals. This double-check procedure
      can further help the employer select appropriate personnel for his or her
      institution. 

PMID- 25562339
TI  - Gendered language attitudes: exploring language as a gendered construct using
      Rasch measurement theory.
AB  - Gendered language attitudes (GLAs) are gender-based perceptions of language
      varieties based on connections between gender-related and linguistic
      characteristics of individuals, including the perception of language varieties as
      possessing degrees of masculinity and femininity. This study combines substantive
      theory about language learning and gender with a model based on Rasch measurement
      theory to explore the psychometric properties of a new measure of GLAs. Findings
      suggest that GLAs is a unidimensional construct and that the items used can be
      used to describe differences among students in terms of the strength of their
      GLAs. Implications for research, theory, and practice are discussed. Special
      emphasis is given to the teaching and learning of languages. 

PMID- 25562340
TI  - Ordered silicon microwire arrays grown from substrates patterned using imprint
      lithography and electrodeposition.
AB  - Silicon microwires grown by the vapor-liquid-solid process have attracted a great
      deal of interest as potential light absorbers for solar energy conversion.
      However, the research-scale techniques that have been demonstrated to produce
      ordered arrays of micro and nanowires may not be optimal for use as high
      throughput processes needed for large-scale manufacturing. Herein we demonstrate
      the use of microimprint lithography to fabricate patterned templates for the
      confinement of an electrodeposited Cu catalyst for the vapor-liquid-solid (VLS)
      growth of Si microwires. A reusable polydimethylsiloxane stamp was used to
      pattern holes in silica sol-gels on silicon substrates, and the Cu catalyst was
      electrodeposited into the holes. Ordered arrays of crystalline p-type Si
      microwires were grown across the sol-gel-patterned substrates with materials
      quality and performance comparable to microwires fabricated with high-purity
      metal catalysts and cleanroom processing. 

PMID- 25562341
TI  - Molecular dynamics simulations of 1-ethyl-3-methylimidazolium
      bis[(trifluoromethyl)sulfonyl]imide clusters and nanodrops.
AB  - Atomistic molecular dynamics simulations of small clusters and nanodroplets of
      the ionic liquid 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide
      [EMIM-Tf2N] subject to an external electric field were performed. A 125-ion-pair
      droplet was found to be nearly spherical with an isotropic distribution of
      cations and anions under vacuum conditions. The droplet was subjected to external
      electric fields of varying strength, and ion emission events were observed. The
      initially spherical droplet is elongated along the electric field axis, resulting
      in nonspherical behavior and increased net dipole values after the application of
      strong electric fields. The critical electric field required for ion field
      emission was determined to be 0.985 V/nm, in agreement with the experimental
      value of 1.0 V/nm. Excellent agreement is found in the prediction of ionic
      emission products for a neutral 125-ion-pair droplet of the ionic liquid at an
      electric field strength of 1.2 V/nm when compared to the results of two
      independent experiments. Small ionic liquid clusters were investigated with
      respect to their thermal stabilities and were found to be thermally stable well
      above room temperature. The role of electric fields in the dissociation of small
      charged ion clusters was also investigated. 

PMID- 25562342
TI  - Development of an asymmetric synthesis of a chiral quaternary FLAP inhibitor.
AB  - A practical sequence involving a noncryogenic stereospecific boronate
      rearrangement followed by a robust formylation with an in situ generated DCM
      anion has been developed for the asymmetric construction of an all-carbon
      quaternary stereogenic center of a FLAP inhibitor. The key boronate rearrangement
      was rendered noncryogenic and robust by using LDA as the base and instituting an
      in situ trapping of the unstable lithiated benzylic carbamate with the boronic
      ester. A similar strategy was implemented for the DCM formylation reaction. It
      was found that the 1,2-boronate rearrangement for the formylation reaction could
      be temperature-controlled, thus preventing overaddition of the DCM anion and
      rendering the process reproducible. The robust stereospecific boronate
      rearrangement and formylation were utilized for the practical asymmetric
      synthesis of a chiral quaternary FLAP inhibitor. 

PMID- 25562343
TI  - Attempted suicide in Ghana: motivation, stigma, and coping.
AB  - To understand the experiences of suicidal persons in Ghana, 10 persons were
      interviewed after they attempted suicide. Thematic analysis of data showed that
      motivation for suicidal behavior included social taunting, hopelessness, and
      partner's infidelity. Suicidal persons reported stigma expressed through physical
      molestation and social ostracism, which left them traumatized. However, they
      coped through social support from relations, religious faith, and use of
      avoidance. Community-wide sensitive education should target reducing stigma and
      also increase mental health education on suicidal behavior in Ghanaian
      communities. 

PMID- 25562344
TI  - Portrait representation of postmenopausal women's experiences of living with
      urinary incontinence.
AB  - This study explored the meaning of the experiences of community-dwelling
      postmenopausal women who were born and grew up in a Muslim country when drawing a
      picture about their lived experiences of urinary incontinence. Hermeneutic
      phenomenology underpinned the study's interpretive research approach. In-depth,
      semistructured interviews were conducted in two sessions with nine postmenopausal
      women. The participants were asked to draw a picture about their lived
      experiences of urinary incontinence in a self-portrait. Three themes emerged to
      illuminate the meaning of urinary incontinence, including "disruption of normal
      functioning," "self-imposed restrictions," and "feeling of despair." Discussion
      of these themes was presented, and practice and research implications were
      suggested. 

PMID- 25562346
TI  - Regenerated teeth: the future of tooth replacement. An update.

PMID- 25562348
TI  - Harnessing the immune response for successful scaffold vascularization.

PMID- 25562345
TI  - Restoring the cornea from limbal stem cells.

PMID- 25562349
TI  - Societal impacts of regenerative medicine: reflections on the views of orthopedic
      professionals.
AB  - As the amount of clinical studies in orthopedic regenerative medicine (RM) is
      increasing, it is time to take into account its impact on society. A total of 36
      biomedical professionals working at the front row of orthopedic RM were
      interviewed to explore their attitudes, opinions and expectations regarding the
      societal impacts of RM. Professionals mainly recognized the societal impacts of
      counteraction of aging, prevention of disease and social justice. The 'soft'
      sides of these impacts were hardly mentioned. Whereas they did not perceive
      themselves in the position to mitigate these impacts, professionals should take
      up their role as actor and become involved in the societal debate. This is
      important as they can co-shape the societal impacts during the developmental
      process of technologies and thereby stimulate responsible innovation. 

PMID- 25562350
TI  - Human mesenchymal stromal cell lysates as a novel strategy to recover liver
      function.
AB  - AIM: It is unknown if the beneficial effects of mesenchymal stromal cells (MSC)
      transplantation into the liver are dependent on their anchorage and
      differentiation into hepatocytes or rather the result of the release of stem cell
      intracellular content with hepatoprotector properties. MATERIALS & METHODS: The
      effects of intact MSC transplantation were compared with the infusion of MSC
      lysates in an experimental rat model of acute liver failure. RESULTS: A more
      powerful hepatoprotective and antiapoptotic effect was obtained after infusion of
      MSC lysates than intact MSC. Changes in IL-6 levels and miRNAs might explain the
      beneficial effects of MSC lysates. CONCLUSION: Infusion of MSC lysates show a
      better hepatoprotective effect than the transplantation of intact MSC.

PMID- 25562351
TI  - A journey from basic stem cell discovery to clinical application: the case of
      adventitial progenitor cells.
AB  - Ischemia is a leading cause of death in the western world. Regenerative medicine
      aims to improve healing of ischemic injury by complementing
      pharmacologic/interventional treatments. Navigating regenerative therapies from
      'bench-to-bedside' is a multistep time-consuming process, balancing cell
      expansion, purity, safety and efficacy while complying with regulatory
      guidelines. Studies started in academic laboratories unused to long-term planning
      often fail because of poor strategy design, lack of contingency plans or funding.
      We provide a strategic insight into our translation of saphenous vein-derived
      adventitial progenitor cells into a clinical grade product to treat angina. We
      discuss discovery phases, introduction of standard operating procedures and
      upgrade to clinical standards. We also examine contractual aspects of
      transferring to GMP-accredited facilities for clinical production and unexpected
      hurdles. 

PMID- 25562352
TI  - The translation of cell-based therapies: clinical landscape and manufacturing
      challenges.
AB  - Cell-based therapies have the potential to make a large contribution toward
      currently unmet patient need and thus effective manufacture of these products is
      essential. Many challenges must be overcome before this can become a reality and
      a better definition of the manufacturing requirements for cell-based products
      must be obtained. The aim of this study is to inform industry and academia of
      current cell-based therapy clinical development and to identify gaps in their
      manufacturing requirements. A total of 1342 active cell-based therapy clinical
      trials have been identified and characterized based on cell type, target
      indication and trial phase. Multiple technologies have been assessed for the
      manufacture of these cell types in order to facilitate product translation and
      future process development. 

PMID- 25562353
TI  - Manufacturing, characterization and control of cell-based medicinal products:
      challenging paradigms toward commercial use.
AB  - During the past decade, a large number of cell-based medicinal products have been
      tested in clinical trials for the treatment of various diseases and tissue
      defects. However, licensed products and those approaching marketing authorization
      are still few. One major area of challenge is the manufacturing and quality
      development of these complex products, for which significant manipulation of
      cells might be required. While the paradigms of quality, safety and efficacy must
      apply also to these innovative products, their demonstration may be demanding.
      Demonstration of comparability between production processes and batches may be
      difficult for cell-based medicinal products. Thus, the development should be
      built around a well-controlled manufacturing process and a qualified product to
      guarantee reproducible data from nonclinical and clinical studies. 

PMID- 25562356
TI  - In situ measurement of magnetization relaxation of internalized nanoparticles in
      live cells.
AB  - Magnetization relaxation mechanisms strongly influence how magnetic nanoparticles
      respond to high-frequency fields in applications such as magnetic hyperthermia.
      The dominant mechanism depends on the mobility of the particles, which will be
      affected in turn by their microenvironment. In this study AC susceptometry was
      used to follow the in situ magnetic response of model systems of blocked and
      superparamagnetic nanoparticles, following their cellular internalization and
      subsequent release by freeze-thaw lysis. The AC susceptibility signal from
      internalized particles in live cells showed only Neel relaxation, consistent with
      measurements of immobilized nanoparticle suspensions. However, Brownian
      relaxation was restored after cell lysis, indicating that the immobilization
      effect was reversible and that nanoparticle integrity was maintained in the
      cells. The results presented demonstrate that cellular internalization can
      disable Brownian relaxation, which has significant implications for designing
      suitable nanoparticles for intracellular hyperthermia applications. Further to
      this, the results highlight the possibility that particles could be released in
      reusable form from degrading cells following hyperthermia treatment, and
      subsequently reabsorbed by viable cells. 

PMID- 25562355
TI  - Gender differences in diet and nutrition among adults initiating antiretroviral
      therapy in Dar es Salaam, Tanzania.
AB  - Human immunodeficiency virus (HIV)-infected males have poor treatment outcomes
      after initiation of antiretroviral therapy (ART) compared to HIV-infected women.
      Dietary factors might mediate the association between sex and disease
      progression. However, the gender difference in diet among HIV-infected
      individuals in sub-Saharan Africa is largely unknown. The objective of this study
      was to examine differences in dietary intake among HIV-infected men and women. We
      conducted a cross-sectional analysis of dietary questionnaire data from 2038
      adults initiating ART in Dar es Salaam, Tanzania to assess whether nutrient
      adequacy differed by sex. We dichotomized participants' nutrient intakes by
      whether recommended dietary allowances (RDAs) were met and estimated the relative
      risk (RR) of meeting RDAs in males using binomial regression models. We also
      estimated the mean difference in intake of foods and food groups by gender. We
      found poorer dietary practices among men compared to women. Males were less
      likely to meet the RDAs for micronutrients critical for slowing disease
      progression among HIV patients: niacin (RR = 0.39, 95% confidence interval [CI]:
      0.27 to 0.55), riboflavin (RR = 0.81, 95% CI: 0.73 to 0.91), vitamin C (RR =
      0.94, 95% CI: 0.89 to 1.00), and zinc (RR = 0.06, 95% CI: 0.01 to 0.24). Intake
      of thiamine, pantothenate, vitamins B6, B12, and E did not vary by gender. Males
      were less likely to eat cereals (mean difference [servings per day] = -0.21, 95%
      CI: -0.44 to 0.001) and vegetables (mean difference = -0.47, 95% CI: -0.86 to 
      0.07) in their diet, but more likely to have meat (mean difference = 0.14, 95%
      CI: 0.06 to 0.21). We conclude that male HIV patients have poorer dietary
      practices than females, and this may contribute to faster progression of the
      disease in males. 

PMID- 25562357
TI  - Cases of adverse reaction to psychotropic drugs and possible association with
      pharmacogenetics.
AB  - Thousands of samples for pharmacogenetic tests have been analysed in our
      laboratory since its establishment. In this article we describe some of the most
      interesting cases of CYP poor metabolisers associated with adverse reactions to
      psychotropic drugs. Prevention of disease/illness, including Adverse Drug
      Reaction (ADR), is an aim of modern medicine. Scientific data supports the fact
      that evaluation of drug toxicology includes several factors, one of which is
      genetic variations in pharmacodynamics and pharmacokinetics of drug pathways.
      These variations are only a part of toxicity evaluation, however, even if it
      would help to prevent only a small percentage of patients from suffering adverse
      drug reactions, especially life threatening ADRs, pharmacogenetic testing should
      play a significant role in any modern psychopharmacologic practice. Medical
      practitioners should also consider the use of other medications or alternative
      dosing strategies for drugs in patients identified as altered metabolisers. This
      will promise not only better and safer treatments for patients, but also
      potentially lowering overall healthcare costs. 

PMID- 25562354
TI  - Adipose-derived stem cells: selecting for translational success.
AB  - We have witnessed a rapid expansion of in vitro characterization and
      differentiation of adipose-derived stem cells, with increasing translation to
      both in vivo models and a breadth of clinical specialties. However, an
      appreciation of the truly heterogeneous nature of this unique stem cell group has
      identified a need to more accurately delineate subpopulations by any of a host of
      methods, to include functional properties or surface marker expression. Cells
      selected for improved proliferative, differentiative, angiogenic or ischemia
      resistant properties are but a few attributes that could prove beneficial for
      targeted treatments or therapies. Optimizing cell culture conditions to permit re
      introduction to patients is critical for clinical translation. 

PMID- 25562359
TI  - An Altered Treatment Plan Based on Direct to Consumer (DTC) Genetic Testing:
      Personalized Medicine from the Patient/Pin-cushion Perspective.
AB  - Direct to consumer (DTC) genomic services facilitate the personalized and
      participatory aspects of "P4" medicine, but raise questions regarding use of
      genomic data in providing predictive and preventive healthcare. We illustrate the
      issues involved by describing a pregnancy management case in which a treatment
      plan was modified based on a DTC result. A woman whose personal and family
      history were otherwise unremarkable for thromboembolism learned through DTC
      testing about the presence of a prothrombin (factor 2) gene mutation (rs1799963).
      Twice daily injections of enoxaparin were recommended throughout pregnancy for
      this patient who, without prior knowledge of this mutation, would not have been
      offered such therapy. Moreover, genetically based medical guidelines are a moving
      target, and treatment of thrombophilic conditions in asymptomatic patients is
      controversial. We address the state of the art in actionable personalized
      medicine with respect to clotting disorders in pregnancy, as well as other
      factors at play- economics, patient preference, and clinical decision support. We
      also discuss what steps are needed to increase the utility of genomic data in
      personalized medicine by collecting information and converting it into actionable
      knowledge. 

PMID- 25562358
TI  - Statin pharmacogenomics: opportunities to improve patient outcomes and healthcare
      costs with genetic testing.
AB  - HMG-CoA reductase inhibitors, commonly known as statins, are some of the most
      widely prescribed medications worldwide and have been shown to be effective at
      lowering cholesterol in numerous long-term prospective trials, yet there are
      significant limitations to their use. First, patients receiving statin therapy
      have relatively low levels of medication adherence compared with other drug
      classes. Next, numerous statin formulations are available, each with its own
      unique safety and efficacy profile, and it may be unclear to prescribers which
      treatment is optimal for their patients. Finally, statins have class-wide side
      effects of myopathy and rhabdomyolysis that have resulted in a product recall and
      dosage limitations. Recent evidence suggests that two genomic markers, KIF6 and
      SLCO1B1, may inform the therapy choice of patients initiating statins. Given the
      prevalence of statin usage, their potential health advantages and their overall
      cost to the healthcare system, there could be significant clinical benefit from
      creating personalized treatment regimens. Ultimately, if this approach is
      effective it may encourage higher adoption of generic statins when appropriate,
      promote adherence, lower rates of myopathy, and overall achieve higher value
      cardiovascular care. This paper will review the evidence for personalized
      prescribing of statins via KIF6 and SLCO1B1 and consider some of the implications
      for testing these markers as part of routine clinical care. 

PMID- 25562360
TI  - Insurance coverage policies for personalized medicine.
AB  - Adoption of personalized medicine in practice has been slow, in part due to the
      lack of evidence of clinical benefit provided by these technologies. Coverage by
      insurers is a critical step in achieving widespread adoption of personalized
      medicine. Insurers consider a variety of factors when formulating medical
      coverage policies for personalized medicine, including the overall strength of
      evidence for a test, availability of clinical guidelines and health technology
      assessments by independent organizations. In this study, we reviewed coverage
      policies of the largest U.S. insurers for genomic (disease-related) and
      pharmacogenetic (PGx) tests to determine the extent that these tests were covered
      and the evidence basis for the coverage decisions. We identified 41 coverage
      policies for 49 unique testing: 22 tests for disease diagnosis, prognosis and
      risk and 27 PGx tests. Fifty percent (or less) of the tests reviewed were covered
      by insurers. Lack of evidence of clinical utility appears to be a major factor in
      decisions of non-coverage. The inclusion of PGx information in drug package
      inserts appears to be a common theme of PGx tests that are covered. This analysis
      highlights the variability of coverage determinations and factors considered,
      suggesting that the adoption of personal medicine will affected by numerous
      factors, but will continue to be slowed due to lack of demonstrated clinical
      benefit. 

PMID- 25562362
TI  - Personalized health care as a pathway for the adoption of genomic medicine.
AB  - While the full promise of genomic medicine may be many years in the future,
      personalized health care (PHC) can begin solving important health care needs now
      and provide a framework for the adoption of genomic technologies as they are
      validated. PHC is a strategic approach to medicine that is individualized,
      predictive, preventive, and involves intense patient engagement. There is great
      need for more effective models of care as nearly half of Medicare patients age 65
      and older have three or more preventable chronic conditions and account for 89%
      of Medicare's growing expenditures. With its focus on reactive care, the current
      health care system is not designed to effectively prevent disease nor manage
      patients with multiple chronic conditions. PHC may be a solution for improving
      care for this population and therefore has been adopted as the delivery platform
      along with a new personalized health plan tool for 230 multi-morbid, homebound
      Medicare recipients in Durham, North Carolina who have been high utilizers of
      health care resources. PHC integrates available personalized health technologies,
      standards of care, and personalized health planning to serve as a model for
      rational health care delivery. Importantly, the PHC model of care will serve as a
      market for emerging predictive and personalized technologies to foster genomic
      medicine. 

PMID- 25562361
TI  - Individual oral therapy with immediate release and effervescent formulations
      delivered by the solid dosage pen.
AB  - New devices enabling freely selectable dosing of solid oral medications are
      urgently needed for personalized medicine. One approach is the use of the
      recently published Solid Dosage Pen, allowing flexible dosing of tablet-like
      sustained release slices from drug loaded extruded strands. Slices were suitable
      for oral single dosed application. The aim of the present study was the
      development of immediate release dosage forms for applications of the device,
      especially for young children. Using two model drugs, two different concepts were
      investigated and evaluated. Effervescent formulations were manufactured by an
      organic wet-extrusion process and immediate release formulations by a melt
      extrusion process. Dissolution experiments were performed for both formulations
      to ensure the immediate release behavior. Extruded strands were individually
      dosed by the Solid Dosage Pen. Various doses of the two formulations were
      analyzed regarding uniformity of mass and content according to pharmacopoeial
      specifications. Proof of concept was demonstrated in both approaches as results
      comply with the regulatory requirements. Furthermore, storing stress tests were
      performed and drug formulations were characterized after storing. The results
      show that suitable packaging material has been selected and storage stability is
      probable. 

PMID- 25562363
TI  - Aligning the economic value of companion diagnostics and stratified medicines.
AB  - The twin forces of payors seeking fair pricing and the rising costs of developing
      new medicines has driven a closer relationship between pharmaceutical companies
      and diagnostics companies, because stratified medicines, guided by companion
      diagnostics, offer better commercial, as well as clinical, outcomes. Stratified
      medicines have created clinical success and provided rapid product approvals,
      particularly in oncology, and indeed have changed the dynamic between drug and
      diagnostic developers. The commercial payback for such partnerships offered by
      stratified medicines has been less well articulated, but this has shifted as the
      benefits in risk management, pricing and value creation for all stakeholders
      become clearer. In this larger healthcare setting, stratified medicine provides
      both physicians and patients with greater insight on the disease and provides
      rationale for providers to understand cost-effectiveness of treatment. This
      article considers how the economic value of stratified medicine relationships can
      be recognized and translated into better outcomes for all healthcare
      stakeholders. 

PMID- 25562365
TI  - Teenagers as a moving target: how can teenagers be encouraged to accept
      treatment?
AB  - Pediatric patients exhibit their own needs and problems and are now considered as
      a real patient group in which downsizing the adult formulation is not the best
      choice and may result in problems. Adolescence (between 12 and 18 years) is a
      transitional period of life from puberty to adulthood and, in this pediatric
      subgroup population, complex problems are observed in compliance with chronic
      treatments. Heterogeneity exists in this group which follows very different and
      sometimes short trends and tendencies and where illness can be a problem leading
      to stigmatization. Influence of social environment as well as friends is complex
      in this period of life. Teenagers have to take care of themselves and be part of
      the treatment including all the features of the social code of this group.
      Particular attention has to be paid to formulation and packaging in order to
      increase compliance and to suit the specific needs of this pediatric subgroup.
      Some examples are given for different drug forms. 

PMID- 25562364
TI  - Pattern of timing adherence could guide recommendations for personalized intake
      schedules.
AB  - Deviations in execution from the prescribed drug intake schedules (timing non
      adherence) are frequent and may pose a substantial risk for therapeutic failure.
      Simple methods to monitor timing adherence with multiple drugs are missing. A new
      technology, i.e., the polymedication electronic monitoring system (POEMS)
      attached to a multidrug punch card, was used in a clinical trial on outpatients
      with prescribed medicines for vascular risk reduction. The complete delineation
      of timing adherence allows for the calculation of objective adherence parameters
      and the linking of exposure with drug-drug interactions. A sub-analysis was
      performed on 68 patients, who were prescribed lipid lowering therapy. A smaller
      intake time variability of the lipid lowering drug was significantly associated
      with better levels of LDL-cholesterol, independently of the time of day. This
      finding may challenge current general recommendations for the timing of lipid
      lowering drugs' intake and substantiate that inter-individual differences in
      timing adherence may contribute to response variability. Thus, objective
      parameters based on multidrug adherence monitoring should be considered as
      independent variables in personalized medicine. In clinical practice,
      personalized intake recommendations according to patients' pattern of timing
      adherence may help to optimize the effectiveness of lipid lowering agents. 

PMID- 25562368
TI  - gamma-Trimethylsilylcyclobutyl carbocation stabilization.
AB  - A series of isomeric 3-trimethylsilyl-1-arylcyclobutyl carbocations, 10 and 11,
      where the cross-ring 3-trimethylsilyl group has the potential to interact with
      the cationic center, have been generated under solvolytic conditions. When the
      cationic center can interact with the rear lobe of the carbon-silicon bond, rate
      enhancements become progressively larger as the substituent on the aryl group
      becomes more electron-withdrawing. When the potential interaction with the
      trimethylsilyl group is via a front lobe interaction, there is minimal rate
      enhancement over the range of substituents. Computational studies have also been
      carried out on these cations 10 and 11. Calculated trimethylsilyl stabilization
      energies progressively increase with electron-withdrawing character of the aryl
      groups when the trimethylsilyl interaction is via the rear lobe. By way of
      contrast, there are minimal changes in stabilization energies when the potential
      trimethylsilyl interaction is via the front lobe of the carbon-silicon bond.
      These computational studies, along with the solvolytic studies, point to a
      significant rear lobe 3-trimethylsilyl stabilization of arylcyclobutyl cations.
      They also argue against any front lobe stabilization of the isomeric
      arylcyclobutyl cations. 

PMID- 25562366
TI  - Investigating the therapeutic potential of herbal leads against drug resistant
      Listeria monocytogenes by computational virtual screening and in vitro assays.
AB  - Listeria monocytogenes, a Gram-positive opportunistic food-borne pathogen,
      naturally resistant to many antibiotics and acquired resistance may be a concern
      in the nearer future. Hence, there is a scope for screening of novel therapeutic
      agents and drug targets, toward the treatment of fatal listeria infections. The
      SecA homologs, SecA1 and SecA2 are the essential components of the general
      secretion (Sec) pathway, a specialised protein export system, present in L.
      monocytogenes. This study evaluates the use of botanicals against L.
      monocytogenes MTCC 1143 by considering SecA proteins as probable drug targets by
      high-throughput screening approaches. The 3D structure of SecA proteins with good
      stereochemical validity was generated by comparative modelling. The druglikeness
      and pharmacokinetic properties of 97 phytoligands identified through the
      extensive literature survey were predicted for druglikeness and ADMET properties.
      The inhibitory properties of best candidates were studied by molecular docking.
      The effect of the selected candidate molecules were further analysed in vitro
      well diffusion and cell aggregation assays. The antibiotic sensitivity profiling
      applied to L. monocytogenes MTCC 1143 using clinically relevant antibiotics
      showed that the bacteria became drug resistant to many tested antibiotics. The
      virtual screening suggested that .05 M cinnamic aldehyde from Cinnamomum camphora
      and 1, 2-Epoxycyclododecane from Cassia auriculata were identified as potential
      SecA inhibitors. The well diffusion assays suggested that the selected herbal
      substances have antibacterial activities. Further, preliminary validation
      suggested that incorporation of cinnamic aldehyde and methanolic or ethyl acetate
      extract of C. auriculata in broth medium shows growth reduction, misassembly and
      cell aggregation. This indicates the inhibition of SecA targets.

PMID- 25562367
TI  - microRNA-328 is a favorable prognostic marker in human glioma via suppressing
      invasive and proliferative phenotypes of malignant cells.
AB  - OBJECTIVE: microRNA (miR)-328 has been reported to be implicated into
      tumorigenesis and tumor progression in human gliomas. However, there were
      controversial study results in relation to its expression pattern as well as
      functions in this disease. The aim of the current study was to determine the
      clinical significance of miR-328 expression in patients with gliomas and its
      effect in tumor cell malignant phenotypes. METHODS: Quantitative real-time PCR
      was performed to detect the expression levels of miR-328 in 116 glioma and 15 non
      neoplastic brain tissues. Then, the correlations of miR-328 expression with
      selected clinicopathologic parameters and clinical outcome of glioma patients
      were statistically evaluated. Moreover, CCK-8 and transwell assays were performed
      to investigate the functions of miR-328 in cell proliferation, invasion and
      migration, respectively. RESULTS: Compared to non-neoplastic brain tissues, the
      expression levels of miR-328 were significantly downregulated in glioma tissues
      (p < 0.001). In addition, miR-328 downregulation was significantly associated
      with WHO grade (p < 0.001) and Karnofsky performance status score (p = 0.02).
      Moreover, glioma patients with low miR-328 expression exhibited markedly shorter
      overall survival than those with high expression (p < 0.001). Furthermore,
      functional assays in vitro system demonstrated that enforced expression of miR
      328 could notably attenuate cell proliferation, invasion and migration of two
      glioma cell lines, including U251 and U87. CONCLUSIONS: Our data offer the
      convincing evidence that loss of miR-328 expression may stimulate advanced tumor
      progression and adverse outcome via promoting cellular proliferation and
      invasion. We propose a tumor suppressive role of miR-328 and its potential
      therapeutic value in human glioma.

PMID- 25562371
TI  - Think globally, act locally.

PMID- 25562369
TI  - Performance of microbial phytases for gastric inositol phosphate degradation.
AB  - Microbial phytases catalyze dephosphorylation of phytic acid, thereby potentially
      releasing chelated iron and improving human iron absorption from cereal-based
      diets. For this catalysis to take place in vivo, the phytase must be robust to
      low pH and proteolysis in the gastric ventricle. This study compares the
      robustness of five different microbial phytases, evaluating thermal stability,
      activity retention, and extent of dephosphorylation of phytic acid in a simulated
      low-pH/pepsin gastric environment and examines secondary protein structural
      changes at low pH via circular dichroism. The Peniophora lycii phytase was found
      to be the most thermostable, but the least robust enzyme in gastric conditions,
      whereas the Aspergillus niger and Escherichia coli phytases proved to be most
      resistant to gastric conditions. The phytase from Citrobacter braakii showed
      intermediate robustness. The extent of loss of secondary structure at low pH
      correlated positively with the extent of activity loss at low pH. 

PMID- 25562372
TI  - Nanosphere monolayer on a transducer for enhanced detection of gaseous heavy
      metal.
AB  - This study reports for the first time that polystyrene monodispersed nanosphere
      monolayer (PS-MNM) based Au (Au-MNM) and Ag (Ag-MNM) nanostructures deposited on
      quartz crystal microbalance (QCM) transducers can be used for nonoptical based
      chemical sensing with extremely high sensitivity and selectivity. This was
      demonstrated by exposing the Au-MNM and Ag-MNM based QCMs to low concentrations
      of Hg(0) vapor in the presence interferent gas species (i.e., H2O, NH3, volatile
      organics, etc.) at operating temperatures of 30 and 75  degrees C. At 30  degrees
      C, the Au-MNM and Ag-MNM based QCMs showed ~16 and ~20 times higher response
      magnitude toward Hg(0) vapor concentration of 3.26 mg/m(3) (364 parts per billion
      by volume (ppbv)) relative to their unmodified control counterparts,
      respectively. The results indicated that the extremely high sensitivity was not
      due to the increased surface area (only 4.62 times increase) but due to their
      long-range interspatial order and high number of surface defect formation which
      are selectively active toward Hg(0) vapor sorption. The Au-MNM and Ag-MNM also
      had more than an order of magnitude lower detection limits (<3 ppbv) toward Hg(0)
      vapor compared to their unmodified control counterparts (>30 ppbv). When the
      operating temperature was increased from 30 to 75  degrees C, it was found that
      the sensors exhibited lower drift, better accuracy, and better selectivity toward
      Hg(0) vapor but at the compromise of higher detection limits. The high
      repeatability (84%), accuracy (97%), and stability of Au-MNM in particular make
      it practical to potentially be used as nonspectroscopic based Hg(0) vapor sensor
      in many industries either as mercury emission monitoring or as part of a mercury
      control feedback system. 

PMID- 25562373
TI  - Surface interrogation of CoP(i) water oxidation catalyst by scanning
      electrochemical microscopy.
AB  - Despite exhaustive spectroscopic investigations on the CoPi oxygen-evolving
      catalyst over the past several years, little is known about the surface cobalt
      sites and intermediates in direct contact with water that are responsible for the
      actual catalysis. Many studies thus far have been limited to ex situ
      characterizations or bulk film measurements, often in the absence of solvent.
      Here we describe an investigation of the CoPi catalyst by surface interrogation
      scanning electrochemical microscopy (SI-SECM). This method should allow us to
      selectively study surface atoms separately from the bulk in a solvent-filled
      environment. By SI-SECM, independent titrations of surface Co(III) and Co(IV)
      were performed, yielding a direct measurement of the surface active-site density
      of a CoPi electrode (11 Co/nm(2)). The pseudo-first-order reaction rate constants
      of Co(III) and Co(IV) with water were determined to be 0.19 and >2 s(-1),
      respectively, through time-dependent titration measurements. 

PMID- 25562370
TI  - Chemical composition and antimicrobial evaluation of the essential oils of
      Bocageopsis pleiosperma Maas.
AB  - Essential oils from the leaves, twigs and barks of Bocageopsis pleiosperma Maas
      were obtained by using hydrodistillation and analysed by using gas chromatography
      coupled to mass spectrometry. Several compounds (51) were detected and
      identified, being beta-bisabolene the main component in all aerial parts of the
      plant, with higher concentration in the leaves (55.77%), followed by barks
      (38.53%) and twigs (34.37%). In order to increase the biological knowledge about
      the essential oil of Bocageopsis species, antimicrobial activities were evaluated
      against the microorganisms Escherichia coli, Staphylococcus epidermidis,
      Enterobacter aerogenes, Candida tropicalis, Candida dubliniensis, Candida
      glabrata and Candida albicans. The essential oil obtained from the barks
      exhibited a moderate effect against S. epidermidis ATCC 1228 (MIC = 250 MUg/mL),
      while the other oils did not exhibit antimicrobial activity. These results
      represent the first report about the chemical composition of B. pleiosperma and
      the first antimicrobial evaluation with a Bocageopsis species.

PMID- 25562374
TI  - Synergetic role of Li(+) during Mg electrodeposition/dissolution in borohydride
      diglyme electrolyte solution: voltammetric stripping behaviors on a Pt
      microelectrode indicative of Mg-Li alloying and facilitated dissolution.
AB  - We describe a voltammetric and spectroscopic study of Mg
      electrodeposition/dissolution (MgDep/Dis) in borohydride diglyme electrolyte
      solution containing Li(+) carried out on a Pt ultramicroelectrode (UME, r = 5
      MUm). The data reveal Li(+) cation facilitation that has not been previously
      recognized in studies made using macroelectrodes. While a single broad,
      asymmetric stripping peak is expected following MgDep on a Pt macroelectrode in
      0.1 M Mg(BH4)2 + 1.5 M LiBH4 diglyme solution on a Pt UME, the stripping reveals
      three resolved oxidation peaks, suggesting that MgDep/Dis consists of not only a
      Mg/Mg(2+) redox reaction but also contributions from Mg-Li alloying/dissolution
      reaction processes. Detailed XPS, SIMS, ICP, and XRD studies were performed that
      confirm the importance of Mg-Li alloy formation processes, the nature of which is
      dependent on the reduction potential used during the MgDep step. Based on the
      electrochemical and surface analysis data, we propose an electrochemical
      mechanism for MgDep/Dis in a borohydride diglyme electrolyte solution that, in
      the presence of 1.5 M Li(+) ions, proceeds as follows: (1) Mg(2+) + 2e(-) ? Mg;
      (2) (1 - x)Mg(2+) + xLi(+) + (2 - x)e(-) ? Mg(1-x)Lix, 0 < x <= 0.02; and (3) (1 
      y)Mg(2+) + yLi(+) + (2 - y)e(-) ? Mg(1-y)Liy, 0.02 < y <= 0.09. Most
      significantly, we find that the potential-dependent MgDep/Dis kinetics are
      enhanced as the concentration of the LiBH4 in the diglyme electrolyte is
      increased, a result reflecting the facilitating influences of reduced
      uncompensated resistance and the enhanced electro-reduction kinetics of Mg(2+)
      due to Mg-Li alloy formation. 

PMID- 25562376
TI  - Dimensional structure of DSM-5 posttraumatic stress disorder symptoms: results
      from the National Health and Resilience in Veterans Study.
AB  - OBJECTIVE: To evaluate the prevalence of DSM-5 posttraumatic stress disorder
      (PTSD) and factor structure of PTSD symptomatology in a nationally representative
      sample of US veterans and examine how PTSD symptom clusters are related to
      depression, anxiety, suicidal ideation, hostility, physical and mental health
      related functioning, and quality of life. METHOD: Data were analyzed from the
      National Health and Resilience in Veterans Study, a nationally representative
      survey of 1,484 US veterans conducted from September through October 2013.
      Confirmatory factor analyses were conducted to evaluate the factor structure of
      PTSD symptoms, and structural equation models were constructed to examine the
      association between PTSD symptom clusters and external correlates. RESULTS: 12.0%
      of veterans screened positive for lifetime PTSD and 5.2% for past-month PTSD. A 5
      factor dysphoric arousal model and a newly proposed 6-factor model both fit the
      data significantly better than the 4-factor model of DSM-5. The 6-factor model
      fit the data best in the full sample, as well as in subsamples of female veterans
      and veterans with lifetime PTSD. The emotional numbing symptom cluster was more
      strongly related to depression (P < .001) and worse mental health-related
      functioning (P < .001) than other symptom clusters, while the externalizing
      behavior symptom cluster was more strongly related to hostility (P < .001).
      CONCLUSIONS: A total of 5.2% of US veterans screened positive for past-month DSM
      5 PTSD. A 6-factor model of DSM-5 PTSD symptoms, which builds on extant models
      and includes a sixth externalizing behavior factor, provides the best dimensional
      representation of DSM-5 PTSD symptom clusters and demonstrates validity in
      assessing health outcomes of interest in this population.

PMID- 25562377
TI  - "Meat juice" is not a homogeneous serological matrix.
AB  - Meat juice samples are used in serological assays to monitor infectious diseases
      within the food chain. However, evidence of inferior sensitivity, presumably due
      to low levels of antibodies in the meat juice compared to serum, has been
      presented, and it has been suggested that adjusting the dilution factor of meat
      juice in proportion to its blood content could improve sensitivity. In the
      present study, the agreement between Toxoplasma gondii-specific immunoglobulin G
      (IgG) levels in meat juice and serum was evaluated, and whether the level of
      immunoglobulins in meat juice was dependent on its blood content. Serum and meat
      juice from diaphragm, heart, tongue, Musculus triceps brachii and M.
      semitendinosus were collected from 20 pigs experimentally infected with T.
      gondii. Analysis of total IgG, heme-containing proteins (hematin), and hemoglobin
      (Hb) revealed significant differences between samples from different muscles,
      with the highest levels in samples from heart and tongue, and the lowest in
      samples from leg muscles. Comparison of T. gondii-specific antibody titers in
      meat juice and serum revealed a strong positive correlation for meat juice from
      heart (rs=0.87; p<0.001), while it was lower for M. semitendinosus (rs=0.71;
      p<0.001) and diaphragm (rs=0.54; p=0.02). Meanwhile, the correlation between
      total IgG and T. gondii titer ratio (meat juice/serum) was highest in diaphragm
      (rs=0.77; p<0.001) followed by M. semitendinosus (rs=0.64; p=0.005) and heart
      (rs=0.50; p=0.051). The correlation between Hb and T. gondii titer ratio was only
      significant for diaphragm (rs=0.65; p=0.008), and for hematin no significant
      correlation was recorded. In conclusion, the specific IgG titers in meat juice
      appeared to depend on the total IgG level, but the correlation to blood (Hb or
      hematin) was poor. Importantly, large significant differences in total IgG levels
      as well as in specific antibody titers were recorded, depending on the muscle the
      meat juice had been extracted from.

PMID- 25562378
TI  - Evolution of electronic structure as a function of layer thickness in group-VIB
      transition metal dichalcogenides: emergence of localization prototypes.
AB  - Layered group-VIB transition metal dichalcogenides (with the formula of MX2) are
      known to show a transition from an indirect band gap in the thick n-monolayer
      stack (MX2)n to a direct band gap at the n = 1 monolayer limit, thus converting
      the system into an optically active material suitable for a variety of
      optoelectronic applications. The origin of this transition has been attributed
      predominantly to quantum confinement effect at reduced n. Our analysis of the
      evolution of band-edge energies and wave functions as a function of n using ab
      initio density functional calculations including the long-range dispersion
      interaction reveals (i) the indirect-to-direct band gap transformation is
      triggered not only by (kinetic-energy controlled) quantum confinement but also by
      (potential-energy controlled) band repulsion and localization. On its own,
      neither of the two effects can explain by itself the energy evolution of the band
      edge states relevant to the transformation; (ii) when n decreased, there emerge
      distinct regimes with characteristic localization prototypes of band-edge states
      deciding the optical response of the system. They are distinguished by the real
      space direct/indirect in combination with momentum-space direct/indirect nature
      of electron and hole states and give rise to distinct types of charge
      distribution of the photoexcited carriers that control excitonic behaviors; (iii)
      the various regimes associated with different localization prototypes are
      predicted to change with modification of cations and anions in the complete MX2
      (M = Cr, Mo, W and X = S, Se, Te) series. These results offer new insight into
      understanding the excitonic properties (e.g., binding energy, lifetime etc.) of
      multiple layered MX2 and their heterostructures. 

PMID- 25562375
TI  - Occupational exposures are associated with worse morbidity in patients with
      chronic obstructive pulmonary disease.
AB  - RATIONALE: Links between occupational exposures and morbidity in individuals with
      established chronic obstructive pulmonary disease (COPD) remain unclear.
      OBJECTIVES: To determine the impact of occupational exposures on COPD morbidity.
      METHODS: A job exposure matrix (JEM) determined occupational exposure likelihood
      based on longest job in current/former smokers (n = 1,075) recruited as part of
      the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had
      established COPD. Bivariate and multivariate linear regression models estimated
      the association of occupational exposure with COPD, and among those with
      established disease, the occupational exposure associations with 6-minute-walk
      distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the
      COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12
      item Short-Form Physical Component (SF-12), and COPD exacerbations requiring
      health care utilization, adjusting for demographics, current smoking status, and
      cumulative pack-years. MEASUREMENTS AND MAIN RESULTS: An intermediate/high risk
      of occupational exposure by JEM was found in 38% of participants. In multivariate
      analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95%
      confidence interval, 1.04-1.97). Among those with COPD, job exposures were
      associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23;
      P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (
      3.3; P < 0.0001); and greater odds of exacerbation requiring health care
      utilization (odds ratio, 1.55; P = 0.03). CONCLUSIONS: Accounting for smoking,
      occupational exposure was associated with COPD risk and, for those with
      established disease, shorter walk distance, greater breathlessness, worse quality
      of life, and increased exacerbation risk. Clinicians should obtain occupational
      histories from patients with COPD because work-related exposures may influence
      disease burden.

PMID- 25562379
TI  - A comparison of the capacity of DSM-IV and DSM-5 acute stress disorder
      definitions to predict posttraumatic stress disorder and related disorders.
AB  - OBJECTIVE: This study addresses the extent to which DSM-IV and DSM-5 definitions
      of acute stress disorder (ASD) predict subsequent posttraumatic stress disorder
      (PTSD) and related psychiatric disorders following trauma. METHOD: Patients with
      randomized admissions to 5 hospitals across Australia (N = 596) were assessed in
      hospital and reassessed for PTSD at 3 (n = 508), 12 (n = 426), 24 (n = 439), and
      72 (n = 314) months using the Clinician-Administered PTSD Scale; DSM-IV
      definition of PTSD was used at each assessment, and DSM-5 definition was used at
      72 months. The Mini-International Neuropsychiatric Interview (MINI) was used at
      each assessment to assess anxiety, mood, and substance use disorders. RESULTS:
      Forty-five patients (8%) met DSM-IV criteria, and 80 patients (14%) met DSM-5
      criteria for ASD. PTSD was diagnosed in 93 patients (9%) at 3, 82 patients (10%)
      at 12, 100 patients (12%) at 24, and 26 patients (8%) at 72 months; 19 patients
      (6%) met DSM-5 criteria for PTSD at 72 months. Comparable proportions of those
      diagnosed with ASD developed PTSD using DSM-IV (3 months = 46%, 12 months = 39%,
      24 months = 32%, and 72 months = 25%) and DSM-5 (43%, 42%, 33%, and 24%) ASD
      definitions. Sensitivity was improved for DSM-5 relative to DSM-IV for depression
      (0.18 vs 0.30), panic disorder (0.19 vs 0.41), agoraphobia (0.14 vs 0.40), social
      phobia (0.12 vs 0.44), specific phobia (0.24 vs 0.58), obsessive-compulsive
      disorder (0.17 vs 0.47), and generalized anxiety disorder (0.20 vs 0.47). More
      than half of participants with DSM-5-defined ASD had a subsequent disorder.
      CONCLUSIONS: The DSM-5 criteria for ASD results in better identification of
      people who will subsequently develop PTSD or another psychiatric disorder
      relative to the DSM-IV criteria. Although prediction is modest, it suggests that
      the new ASD diagnosis can serve a useful function in acute trauma settings for
      triaging those who can benefit from either early intervention or subsequent
      monitoring.

PMID- 25562380
TI  - Structural basis of ligand binding to UDP-galactopyranose mutase from
      Mycobacterium tuberculosis using substrate and tetrafluorinated substrate
      analogues.
AB  - UDP-Galactopyranose mutase (UGM) is a flavin-containing enzyme that catalyzes the
      reversible conversion of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose
      (UDP-Galf) and plays a key role in the biosynthesis of the mycobacterial cell
      wall galactofuran. A soluble, active form of UGM from Mycobacterium tuberculosis
      (MtUGM) was obtained from a dual His6-MBP-tagged MtUGM construct. We present the
      first complex structures of MtUGM with bound substrate UDP-Galp (both oxidized
      flavin and reduced flavin). In addition, we have determined the complex
      structures of MtUGM with inhibitors (UDP and the dideoxy-tetrafluorinated
      analogues of both UDP-Galp (UDP-F4-Galp) and UDP-Galf (UDP-F4-Galf)), which
      represent the first complex structures of UGM with an analogue in the furanose
      form, as well as the first structures of dideoxy-tetrafluorinated sugar analogues
      bound to a protein. These structures provide detailed insight into ligand
      recognition by MtUGM and show an overall binding mode similar to those reported
      for other prokaryotic UGMs. The binding of the ligand induces conformational
      changes in the enzyme, allowing ligand binding and active-site closure. In
      addition, the complex structure of MtUGM with UDP-F4-Galf reveals the first
      detailed insight into how the furanose moiety binds to UGM. In particular, this
      study confirmed that the furanoside adopts a high-energy conformation ((4)E)
      within the catalytic pocket. Moreover, these investigations provide structural
      insights into the enhanced binding of the dideoxy-tetrafluorinated sugars
      compared to unmodified analogues. These results will help in the design of
      carbohydrate mimetics and drug development, and show the enormous possibilities
      for the use of polyfluorination in the design of carbohydrate mimetics. 

PMID- 25562381
TI  - Validation of inhalation provocation test in chronic bird-related
      hypersensitivity pneumonitis and new prediction score.
AB  - RATIONALE: Hypersensitivity pneumonitis (HP) is an immunologically mediated lung
      disease induced by the inhalation of any of a wide variety of antigens. For
      example, bird-related HP (BRHP) results from the inhalation of avian antigens.
      The clinical features of chronic HP, including imaging and histological findings,
      are similar to those of idiopathic pulmonary fibrosis. Despite its status as the
      "gold standard," the inhalation provocation test (IPT) is rarely performed,
      because the methods and the criteria are not standardized. In 2000, we reported
      the utility of IPT for pigeon dropping extracts. OBJECTIVES: The purpose of the
      current study was to validate the utility and safety of the test, and to
      differentiate chronic HP from other interstitial lung diseases. METHODS: A total
      of 28 patients with chronic BRHP and 19 control subjects were evaluated in this
      retrospective study. We validated the previous criteria and proposed new criteria
      using prediction scores. MEASUREMENTS AND MAIN RESULTS: In the IPT using pigeon
      dropping extracts, the previous criteria showed a sensitivity of 78.6% and a
      specificity of 94.7% in this retrospective study. The increases in the peripheral
      white blood cell count and C-reactive protein levels are good indicators of a
      positive response to the inhalation challenge. We propose the use of the IPT
      prediction score (?WBC [%] + 2 * ?P[a - a]O2 [mm Hg], where WBC is white blood
      cell) and the prediction rule, which showed high sensitivity and specificity
      values of 92.9 and 94.7%, respectively. Two (1.5%) out of a total of 130 subjects
      who underwent the tests required treatment after the challenge. CONCLUSIONS: The
      IPT is a useful and safe tool for the diagnosis of chronic HP. The IPT prediction
      score that we have proposed has high sensitivity and specificity in the diagnosis
      of chronic BRHP.

PMID- 25562383
TI  - Uniform circular disks with synthetically tailorable diameters: two-dimensional
      nanoparticles for plasmonics.
AB  - Herein, we report the synthesis of structurally uniform gold circular disks as
      two-dimensional plasmonic nanostructures that complement the well-established one
      dimensional rod and three-dimensional shell structures. We show that a Au
      conproportionation reaction can be used to etch a collection of nonuniform
      triangular prisms into a uniform circular disk product with thickness and
      diameter varying <10%. These new particles have broadly tunable plasmon
      resonances (650-1000 nm) with narrow bandwidths (0.23-0.28 eV) and can be
      described as "effectively two-dimensional" plasmonic structures, as they do not
      support a significant transverse mode. 

PMID- 25562382
TI  - Hypoxia-guided adaptive radiation dose escalation in head and neck carcinoma: a
      planning study.
AB  - OBJECTIVE: To evaluate from a planning point of view the dose distribution of
      adaptive radiation dose escalation in head and neck squamous cell carcinoma
      (HNSCC) using (18)F-Fluoroazomycin arabinoside (FAZA) positron emission
      tomography/computed tomography (PET-CT). MATERIAL/METHODS: Twelve patients with
      locally advanced HNSCC underwent three FAZA PET-CT before treatment, after 7
      fractions and after 17 fractions of a carboplatin-5FU chemo-radiotherapy regimen
      (70 Gy in 2 Gy per fraction over 7 weeks). The dose constraints were that every
      hypoxic voxel delineated before and during treatment (newborn hypoxic voxels)
      should receive a total dose of 86 Gy. A median dose of 2.47 Gy per fraction was
      prescribed on the hypoxic PTV defined on the pre-treatment FAZA PET-CT; a median
      dose of 2.57 Gy per fraction was prescribed on the newborn voxels identified on
      the first per-treatment FAZA PET-CT; a median dose of 2.89 Gy per fraction was
      prescribed on the newborn voxels identified on the second per-treatment FAZA PET
      CT. RESULTS: Ten of 12 patients had hypoxic volumes. Six of 10 patients completed
      all the FAZA PET-CT during radiotherapy. For the hypoxic PTVs, the average D50%
      matched the prescribed dose within 2% and the homogeneity indices reached 0.10
      and 0.12 for the nodal PTV 86 Gy and the primary PTV 86 Gy, respectively.
      Compared to a homogeneous 70 Gy mean dose to the PTVs, the dose escalation up to
      86 Gy to the hypoxic volumes did not typically modify the dose metrics on the
      surrounding normal tissues. CONCLUSION: From a planning point of view, FAZA-PET
      guided dose adaptive escalation is feasible without substantial dose increase to
      normal tissues above tolerance limits. Clinical prospective studies, however,
      need to be performed to validate hypoxia-guided adaptive radiation dose
      escalation in head and neck carcinoma.

PMID- 25562384
TI  - Histochemical structure and immunolocalisation of the hyaluronan system in the
      dromedary oviduct.
AB  - We investigated the local modulation of some histochemical properties of oviducts
      of the dromedary (Camelus dromedarius), focusing on the immnolocalisation of
      hyaluronic acid (HA) synthases (HAS2 and HAS3), hyaluronidases (HYAL2 and HYAL1)
      and the HA receptor CD44 in the ampulla and isthmus. Abundant acidic
      mucopolysaccharides (glycosaminoglycans) were detected by Alcian blue staining
      along the luminal surface of both ciliated and non-ciliated epithelial cells
      (LE). Staining for HAS2 was higher in the primary epithelial folds of the ampulla
      compared with the isthmus, especially in secretory cells, adluminal epithelial
      surface and supranuclear cell domain. HAS3 staining was stronger in the LE of the
      isthmus than ampulla. HYAL2 was detected in the LE in the ampulla and isthmus and
      was more intense in the adluminal projections of secretory cells. HYAL1 was
      weakly detected in the LE with no difference between the ampulla and isthmus.
      Strong CD44 immunostaining was present in the LE of the ampulla and isthmus. CD44
      staining was higher in secretory cells than in ciliated epithelial cells and was
      higher in the supranuclear region than the basal region of the cytoplasm. In
      conclusion, we provide evidence that HA synthesis and turnover occur in the camel
      oviduct. Differences in HAS2 and HAS3 expression suggest regional differences in
      the molecular size of HA secreted in oviductal fluid that may influence oviduct
      gamete interaction in the camel.

PMID- 25562385
TI  - Soluble CD14 is associated with markers of vascular dysfunction in bariatric
      surgery patients.
AB  - BACKGROUND: Chronic endotoxemia has been proposed to contribute to obesity
      related complications. We aimed to investigate the potential impact of
      lipopolysaccharide (LPS) and subsequent monocyte activation measured as soluble
      CD14 (sCD14) on markers of vascular dysfunction in obese subjects undergoing
      bariatric surgery. METHODS: This was a prospective study of 49 obese patients and
      17 controls, assessed by plasma levels of LPS, sCD14, asymmetric dimethylarginine
      (ADMA), and symmetric dimethylarginine (SDMA). RESULTS: Levels of ADMA were
      increased in obese subjects compared to controls, but were not significantly
      reduced after bariatric surgery. In obese subjects at baseline, there was a
      significant trend to increasing levels of ADMA and SDMA through tertiles of sCD14
      and decreasing levels of both markers through tertiles of LPS. In models
      adjusting for age and gender, sCD14 but not LPS remained independently associated
      with ADMA and SDMA. For every 10% age- and gender-adjusted increase in sCD14,
      ADMA increased 0.031 MUM (5.6%), whereas SDMA increased 0.039 MUM (10.8%).
      CONCLUSIONS: Our results suggest that monocyte activation as measured by sCD14 is
      associated with obesity-related vascular dysfunction, whereas potential upstream
      triggers including microbial products should be investigated in future studies.

PMID- 25562387
TI  - Using an airbrush pen for layer-by-layer growth of continuous perovskite thin
      films for hybrid solar cells.
AB  - In this manuscript we describe hybrid heterojunction solar cells, having the
      device architecture glass/indium tin oxide/poly(3,4
      ethylenedioxythiopene)/poly(styrenesulfonic acid)/perovskite/[6,6]-phenyl-C61
      butyric acid methyl ester/C60/2,9-dimethyl- 4,7-diphenyl-1,10-phenanthroline/Al,
      fabricated using lead halide perovskite obtained through spray-coating at a low
      precursor concentration. To study the relationship between the morphology and
      device performance, we recorded scanning electron microscopy images of perovskite
      films prepared at various precursor ratios, spray volumes, substrate
      temperatures, and postspray annealing temperatures. Optimization of the spray
      conditions ensured uniform film growth and high surface area coverage at low
      substrate temperatures. Lead halide perovskite solar cells prepared under the
      optimal conditions displayed an average power conversion efficiency (PCE) of
      approximately 9.2%, with 85% of such devices having efficiencies of greater than
      8.3%. The best-performing device exhibited a short-circuit current density of
      17.3 mA cm(-2), a fill factor of 0.63, and an open-circuit voltage of 0.93 V,
      resulting in a PCE of 10.2%. Because spray-coating technology allows large-area
      deposition, we also fabricated devices having areas of 60 and 342 mm(2),
      achieving PCEs with these devices of 6.88 and 4.66%, respectively. 

PMID- 25562386
TI  - Comparison of Cardiomyocyte Differentiation Potential Between Type 1 Diabetic
      Donor- and Nondiabetic Donor-Derived Induced Pluripotent Stem Cells.
AB  - Type 1 diabetes mellitus (T1DM) is the most common type of diabetes in children
      and adolescents. Diabetic subjects are more likely to experience a myocardial
      infarction compared to nondiabetic subjects. In recent years, induced pluripotent
      stem cells (iPSCs) have received increasing attention from basic scientists and
      clinicians and hold promise for myocardial regeneration due to their unlimited
      proliferation potential and differentiation capacity. However, cardiomyogenesis
      of type 1 diabetic donor-derived iPSCs (T1DM-iPSCs) has not been investigated
      yet. The aim of the study was to comparatively analyze cardiomyocyte (CM)
      differentiation capacity of nondiabetic donor-derived iPSCs (N-iPSCs) and T1DM
      iPSCs. The differentiated CMs were confirmed by both expression of cardiac
      specific markers and presence of cardiac action potential. Since mitochondrial
      bioenergetics is vital to every aspect of CM function, extracellular
      acidification rates and oxygen consumption rates were measured using Seahorse
      extracellular flux analyzer. The results showed that N-iPSCs and T1DM-iPSCs
      demonstrated similar capacity of differentiation into spontaneously contracting
      CMs exhibiting nodal-, atrial-, or ventricular-like action potentials.
      Differentiation efficiency was up to 90%. In addition, the CMs differentiated
      from N-iPSCs and T1DM-iPSCs (N-iPSC-CMs and T1DM-iPSC-CMs, respectively) showed
      1) well-regulated glucose utilization at the level of glycolysis and
      mitochondrial oxidative phosphorylation and 2) the ability to switch metabolic
      pathways independent of extracellular glucose concentration. Collectively, we
      demonstrate for the first time that T1DM-iPSCs can differentiate into functional
      CMs with well-regulated glucose utilization as shown in N-iPSCs, suggesting that
      T1DM-iPSC-CMs might be a promising autologous cell source for myocardial
      regeneration in type 1 diabetes patients. 

PMID- 25562388
TI  - Exercise for Mild Balance Dysfunction: Research into Practice.
AB  - The objective of this study was to determine whether improved balance outcomes
      achieved in a randomized controlled trial (RCT) using balance screening to
      identify mild balance dysfunction and home exercises could be translated into
      community settings. Community-dwelling people aged over 65 who expressed concerns
      about their balance, had less than two falls in the preceding 12 months, and who
      had mild balance impairment on screening were given an individualized home-based
      balance and strengthening exercise program with intermittent home-visit support
      by a physiotherapist. Of 71 participants assessed (mean age 77.3 years, 76%
      female), 58 (82%) completed the six-month intervention. Twenty six percent of
      participants regained balance performance within normal limits--similar to those
      achieved in the previous RCT. Successful results from a previous RCT were able to
      be translated into community settings, with a similar magnitude of effect on
      balance and mobility.

PMID- 25562389
TI  - Impulsive force on the head during performance of typical ukemi techniques
      following different judo throws.
AB  - In this study, eight judo athletes who are major candidates for the Japan
      national team were recruited as participants. Kinematic analysis of exemplary
      ukemi techniques was carried out using two throws, o-soto-gari, a throw linked to
      frequent injury, and o-uchi-gari. The aim of this study was to kinematically
      quantify the timing patterns of exemplary ukemi techniques and to obtain
      kinematic information of the head, in a sequence of ukemi from the onset of the
      throw to the completion of ukemi. The results indicated that the vertical
      velocity with which the uke's head decelerated was reduced by increasing the body
      surface exposed to the collision with the tatami and by increasing the elapsed
      time. In particular, overall upper limb contact with the tatami is greatly
      associated with deceleration. In o-soto-gari, the impulsive force on the faller's
      head as the head reached the lowest point was 204.82 +/- 19.95 kg m . s(-2) while
      in o-uchi-gari it was 118.46 +/- 63.62 kg m . s(-2), z = -1.75, P = 0.08, and it
      did present a large-sized effect with r = 0.78. These findings indicate that the
      exemplary o-soto-gari as compared to o-uchi-gari is the technique that causes
      more significant damage to the uke's head.

PMID- 25562390
TI  - Skin autofluorescence and complications of diabetes: does ethnic background or
      skin color matter?
AB  - AIMS: Skin autofluorescence (AF) has been associated with complications of
      diabetes. We evaluated the influence of skin color and ethnicity on the
      association between skin AF and the presence of diabetes-related complications.
      MATERIALS AND METHODS: In a multiethnic type 2 diabetes cohort we investigated
      all patients with available skin AF measurements. The associations between skin
      AF and hemoglobin A1c (HbA1c) and the presence of complications of diabetes were
      estimated, stratified for ethnicity and quartiles of ultraviolet reflectance
      percentage (R%). RESULTS: In total, 810 patients (438 native Dutch, 372 non
      Dutch) were included. Because of too low an R%, 32% of black Africans and 19% of
      Hindustanis were excluded. Non-Dutch patients had lower AF values compared with
      Dutch patients (median AF=2.69 [interquartile range (IQR), 2.26-3.09] vs. 3.06
      [IQR, 2.65-3.50] arbitrary units; P<0.001), but the R% was also lower (non-Dutch,
      median R%=12% [IQR, 9-15%]; Dutch, median R%=18% [IQR, 14-23%]; P=0.027). In the
      multivariate analysis, skin AF was only a determinant for complications in
      patients with R% 25(th) percentile (macrovascular, odds ratio [OR]=1.71 [95%
      confidence interval (CI), 1.05-2.77] vs. 1.15 [95% CI, 0.55-2.40] in the lowest
      quartile of R%; microvascular, OR=1.81 [95% CI, 1.20-2.75] vs. OR=0.87 [95% CI,
      0.50-1.51]). A similar pattern was observed for nephropathy, neuropathy, and
      retinopathy separately. In non-Dutch patients AF was not a significant
      determinant for diabetes complication risk, whereas HbA1c was for nephropathy,
      retinopathy, and neuropathy. CONCLUSIONS: Skin AF measurement is a valuable tool
      for the assessment of micro- and macrovascular complication risk in patients with
      light skin color types. Even after exclusion of patients with too low a
      reflectance, the current performance of the AGE ReaderTM (DiagnOptics
      Technologies BV, Groningen, The Netherlands) was insufficient in darker-skinned
      patients.

PMID- 25562391
TI  - Sexuality in older Spanish women: voices and reflections.
AB  - Our research has been aimed at understanding the experience, practice, and sexual
      life in a group of Spanish women over 50 years of age. We studied a sample of 729
      women between 50 and 80 years old. Our results provide qualitative and
      quantitative information and important insights about the sexual life of Spanish
      women and identify differences in the experience and reality of sexual life after
      the age of 70. The status of having or lacking a partner, and a personal interest
      in emotional relationships and sexual practices, are elements that determine the
      possibility of enjoying a satisfying postmenopausal sexuality. 

PMID- 25562392
TI  - Tetrahydrofuranyl and tetrahydropyranyl protection of amino acid side-chains
      enables synthesis of a hydroxamate-containing aminoacylated tRNA.
AB  - The ability to specifically engineer metal binding sites into target proteins has
      far-reaching consequences ranging from the development of new biocatalysts and
      imaging reagents to the production of proteins with increased stability. We
      report the efficient tRNA-mediated incorporation of the hydroxamate containing
      amino acid, N(epsilon)-acetyl-N(epsilon)-hydroxy-L-lysine, into a transcription
      factor (TFIIIA). Because this amino acid is compact, hydrophilic, and uncharged
      at physiological pH, it should have little or no effect on protein folding or
      solubility. The N(epsilon)-hydroxy group of the hydroxamate is refractory to
      photodeprotection and required the identification of reagents for O-protection
      that are compatible with the synthesis of acylated tRNA. Tetrahydrofuranyl and
      tetrahydropyranyl O-protecting groups can be removed using mild acid conditions
      and allowed for an orthogonal protection strategy in which deprotection of the
      amino acid side chain precedes ligation of an acylated dinucleotide to a
      truncated suppressor tRNA. These protecting groups will provide a valuable
      alternative for O-protection, especially in cases where photodeprotection cannot
      be used.

PMID- 25562393
TI  - A fundamental study on the [(MU-Cl)3Mg2(THF)6]+ dimer electrolytes for
      rechargeable Mg batteries.
AB  - The long sought solvated [MgCl](+) species in the Mg-dimer electrolytes was
      characterized by soft mass spectrometry. The presented study provides an
      insightful understanding on the electrolyte chemistry of rechargeable Mg
      batteries. 

PMID- 25562395
TI  - Label free detection of nucleic acids by modulating nanochannel surfaces.
AB  - We develop surface-modified 100 nm silica nanofluidic channels that change in
      measured conductivity upon exposure to single- or double-stranded DNA. Through
      careful monitoring of both electromigrative and advective current in the channel,
      we can detect nanomolar concentrations of DNA. These results can be exploited for
      inexpensive, all-electronic DNA sensors. 

PMID- 25562394
TI  - Glucose transport machinery reconstituted in cell models.
AB  - Here we demonstrate the production of a functioning cell model by formation of
      giant vesicles reconstituted with the GLUT1 glucose transporter and a glucose
      oxidase and hydrogen peroxidase linked fluorescent reporter internally. Hence, a
      simplified artificial cell is formed that is able to take up glucose and process
      it. 

PMID- 25562396
TI  - Gamma irradiated chitosan and its derivatives as antioxidants for minced chicken.
AB  - Ionizing radiation and oxidizing agent like H2O2 were used to degrade chitosan
      (CS) and its derivatives; N-maleoylchitosan (NMCS), and N-phthaloylchitosan
      (NPhCS). The structure changes were detected using gel permeation chromatography
      (GPC). The results revealed that ionizing radiation degraded CS, MNCS, NPhCS and
      altered their molecular weights and antioxidant activity. The higher the
      irradiation dose, the lower the molecular weight and the higher antioxidant
      activity. The addition of irradiated CS and NMCS to minced chicken resulted in
      highly significant reduction in malondialdehyde (MDA) content (50 and 70%,
      respectively) if compared with the control. The irradiated NMCS toxicity study
      did not show strong proliferative effect at small concentrations or cytotoxic
      effects at higher concentrations. The obtained results suggested that CS and NMCS
      could be used as natural antioxidant for improving the oxidative deterioration of
      minced chicken during refrigerated storage. 

PMID- 25562397
TI  - Metal-free, one-pot, sequential protocol for transforming alpha,beta-epoxy
      ketones to beta-hydroxy ketones and alpha-methylene ketones.
AB  - A new sequential, one-pot protocol for transforming 1,3-disubstituted 2,3-epoxy
      ketones to beta-hydroxy ketones and alpha-methylene ketones has been developed.
      Reaction of epoxy ketones with boron trifluoride etherate (BF3.OEt2) generates
      the cationic intermediates by regioselective epoxide ring opening and an acyl
      shift. Then, a treatment of these cations with 2-aryl-1,3
      dimethylbenzimidazolines (DMBIH) results in formation of 1,2-disubstituted 3
      hydroxy ketones. DMBIH serves as a hydride donor in the second step of this
      process. Finally, the beta-hydroxy ketones can be converted to 1,2-disubstituted
      2-methylene ketones by treatment with methanesulfonic acid or a combination of
      methanesulfonyl chloride and triethylamine. Importantly, the sequential steps
      involved in formation of the alpha-methylene ketone products can be carried out
      in one pot. 

PMID- 25562398
TI  - High-throughput fabrication and screening improves gold nanoparticle
      chemiresistor sensor performance.
AB  - Chemiresistor sensor arrays are a promising technology to replace current
      laboratory-based analysis instrumentation, with the advantage of facile
      integration into portable, low-cost devices for in-field use. To increase the
      performance of chemiresistor sensor arrays a high-throughput fabrication and
      screening methodology was developed to assess different organothiol
      functionalized gold nanoparticle chemiresistors. This high-throughput fabrication
      and testing methodology was implemented to screen a library consisting of 132
      different organothiol compounds as capping agents for functionalized gold
      nanoparticle chemiresistor sensors. The methodology utilized an automated liquid
      handling workstation for the in situ functionalization of gold nanoparticle films
      and subsequent automated analyte testing of sensor arrays using a flow-injection
      analysis system. To test the methodology we focused on the discrimination and
      quantitation of benzene, toluene, ethylbenzene, p-xylene, and naphthalene (BTEXN)
      mixtures in water at low microgram per liter concentration levels. The high
      throughput methodology identified a sensor array configuration consisting of a
      subset of organothiol-functionalized chemiresistors which in combination with
      random forests analysis was able to predict individual analyte concentrations
      with overall root-mean-square errors ranging between 8-17 MUg/L for mixtures of
      BTEXN in water at the 100 MUg/L concentration. The ability to use a simple sensor
      array system to quantitate BTEXN mixtures in water at the low MUg/L concentration
      range has direct and significant implications to future environmental monitoring
      and reporting strategies. In addition, these results demonstrate the advantages
      of high-throughput screening to improve the performance of gold nanoparticle
      based chemiresistors for both new and existing applications. 

PMID- 25562400
TI  - Introductory lecture: the physical chemistry of functionalised biomedical
      nanoparticles.

PMID- 25562399
TI  - Role of charge regulation and size polydispersity in nanoparticle encapsulation
      by viral coat proteins.
AB  - Nanoparticles can be encapsulated by virus coat proteins if their surfaces are
      functionalized to acquire a sufficiently large negative charge. A minimal surface
      charge is required to overcome (i) repulsive interactions between the positively
      charged RNA-binding domains on the proteins and (ii) the loss of mixing and
      translational entropy of RNA and capsid coat proteins. Here, we present a model
      describing the encapsulation of spherical particles bearing weakly acidic surface
      groups and investigate how charge regulation and size polydispersity impact upon
      the encapsulation efficiency of gold nanoparticles by model coat proteins. We
      show that the surface charge density of these particles cannot be assumed fixed,
      but that it adjusts itself to minimize electrostatic repulsion between the
      charges on them and maximize the attractive interaction with the RNA binding
      domains on the proteins. Charge regulation in combination with the natural
      variation of particle radii has a large effect on the encapsulation efficiency:
      it makes it much more gradual despite its inherently cooperative nature. Our
      calculations rationalize recent experimental observations on the coassembly of
      gold nanoparticles by brome mosaic virus coat proteins. 

PMID- 25562401
TI  - Variable motor imagery training induces sleep memory consolidation and transfer
      improvements.
AB  - Motor-skill practice in repetitive or variable orders leads to better within-day
      acquisition and facilitates retention and transfer, respectively. This practice
      pattern effect has been robustly found for physical practice, but little is known
      about its effect after motor imagery (MI) practice. In the present study, we
      investigated the effect of constant or variable MI practice, and the
      consolidation following a day-time or a sleep interval. The physical performance
      was assessed before (pre-test) and after MI training (post-test), as well as
      after a night or day-time consolidation (retention test). Finally, a transfer
      test on an unpracticed task was further performed. Results revealed that in all
      participants, performance increased significantly in the post-test when compared
      with the pre-test, while only subjects in the variable MI training showed further
      gains in performance in the retention test following a night of sleep, and
      exhibited the best transfer of performance to a novel visuomotor sequence. In
      contrast, subjects in the constant MI training did not show any delayed
      performance gain following both day and sleep-consolidation. Overall, and for the
      first time, these findings partially support the practice pattern effect of motor
      learning with MI, and further highlight a new difference between mental and
      physical practice, especially on consolidation. To conclude, variable MI
      practice, rather than constant, seems to be the valuable condition that should be
      considered in the practical implications of mental training in motor learning and
      rehabilitation. 

PMID- 25562402
TI  - Exploring allosteric activation of LigAB from Sphingobium sp. strain SYK-6
      through kinetics, mutagenesis and computational studies.
AB  - The protocatechuate 4,5-dioxygenase (LigAB) from Sphingobium sp. strain SYK-6 is
      the defining member of the Type II extradiol dioxygenase superfamily (a.k.a. PCA
      Dioxygenase Superfamily or PCADSF) and plays a key aromatic ring-opening role in
      the metabolism of several lignin derived aromatic compounds. In our search for
      alternate substrates and inhibitors of LigAB, we discovered allosteric rate
      enhancement in the presence of non-substrate protocatechuate-like aldehydes such
      as vanillin. LigAB has the broadest substrate utilization profile of all
      protocatechuate (PCA) 4,5-dioxygenase described in the literature, however, the
      rate enhancement is only observed with PCA, with vanillin increasing kcat for
      LigAB by 36%. Computational docking has identified a potential site of allosteric
      binding near the entrance to the active site. Examination of a multiple sequence
      alignment reveals that many of the residues contributing to this newly identified
      allosteric pocket are highly conserved within the LigB family of the PCADSF.
      Point mutants of Phe103alpha and Ala18beta, two residues located in the putative
      allosteric pocket, display altered rate enhancement as compared to LigAB-WT,
      providing support for the computationally identified allosteric binding site.
      Further investigation of this binding site may provide insight into the mechanism
      of this never before observed allosteric activation in extradiol dioxygenases. 

PMID- 25562403
TI  - Sulfated and sulfonated polymers are able to solubilize efficiently the protein
      aggregates of different nature.
AB  - The search for new ways to suppress unwanted protein aggregation represents an
      important problem in modern biochemistry, bioengineering, and even medicine.
      Recently we succeeded in preventing the aggregation using synthetic
      polyelectrolytes. The present work describes a new approach to solubilizing pre
      formed protein aggregates with sulfated or sulfonated polymers (polysulfoanions).
      For the first time it was shown that polysulfoanions are capable of solubilizing
      amorphous and amyloid protein inclusion bodies as well as thermal aggregates.
      Treatment of prion protein inclusion bodies with sulfonated polymers was shown to
      cause significant decrease in amyloid structure content, whereas in case of
      thermal aggregates of glyceraldehyde-3-phosphate dehydrogenase the observed
      solubilization was accompanied by a partial recovery of enzymatic activity. The
      suggested approach could be relevant in the task of extracting recombinant
      proteins from inclusion bodies and also useful in the development of amyloid
      disease therapy. 

PMID- 25562404
TI  - On the relationship between low-frequency normal modes and the large-scale
      conformational changes of proteins.
AB  - Normal mode analysis is a computational technique that allows to study the
      dynamics of biological macromolecules. It was first applied to small protein
      cases, more than thirty years ago. The interest in this technique then raised
      when it was realized that it can provide insights about the large-scale
      conformational changes a protein can experience, for instance upon ligand
      binding. As it was also realized that studying highly simplified protein models
      can provide similar insights, meaning that this kind of analysis can be both
      quick and simple to handle, several applications were proposed, in the context of
      various structural biology techniques. This review focuses on these applications,
      as well as on how the functional relevance of the lowest-frequency modes of
      proteins was established. 

PMID- 25562405
TI  - Elucidating the crucial role of hole injection layer in degradation of organic
      light-emitting diodes.
AB  - Although the luminous efficiency has been significantly improved in multilayered
      organic light-emitting diodes (OLEDs), understanding the major factors that
      influence degradation of OLEDs remains a major challenge due to their complex
      device structure. In this regard, we elucidate the crucial role of hole injection
      layer (HIL) in degradation of OLEDs by using systematically controlled hole
      injection interfaces. To analyze charge injection dependent degradation mechanism
      of OLEDs, we fabricate multilayered small-molecule OLEDs with molecularly
      controlled HILs. Although a reduced hole injection energy barrier greatly
      improves both a luminous efficiency and an operational lifetime (>10 times) of
      the OLEDs at the same time, large hole injection energy barrier increasingly
      aggravates its charge injection and transport during device operation. By using
      various kinds of nondestructive analyses at gradual stages of degradation, we
      demonstrate that accumulated charges at interfaces due to inefficient charge
      injection accelerates rate of device degradation. 

PMID- 25562406
TI  - Identification of highly active Fe sites in (Ni,Fe)OOH for electrocatalytic water
      splitting.
AB  - Highly active catalysts for the oxygen evolution reaction (OER) are required for
      the development of photoelectrochemical devices that generate hydrogen
      efficiently from water using solar energy. Here, we identify the origin of a 500
      fold OER activity enhancement that can be achieved with mixed
      (Ni,Fe)oxyhydroxides (Ni(1-x)Fe(x)OOH) over their pure Ni and Fe parent
      compounds, resulting in one of the most active currently known OER catalysts in
      alkaline electrolyte. Operando X-ray absorption spectroscopy (XAS) using high
      energy resolution fluorescence detection (HERFD) reveals that Fe(3+) in Ni(1
      x)Fe(x)OOH occupies octahedral sites with unusually short Fe-O bond distances,
      induced by edge-sharing with surrounding [NiO6] octahedra. Using computational
      methods, we establish that this structural motif results in near optimal
      adsorption energies of OER intermediates and low overpotentials at Fe sites. By
      contrast, Ni sites in Ni(1-x)Fe(x)OOH are not active sites for the oxidation of
      water.

PMID- 25562407
TI  - Structured decision-making: using personalized medicine to improve the value of
      cancer care.
AB  - Cancer care is often inconsistently delivered with inadequate incorporation of
      patient values and objective evidence into decision-making. Utilization of time
      limited trials of care with predefined decision points that are based on
      iteratively updated best evidence, tools that inform providers about a patient's
      experience and values, and known information about a patient's disease will allow
      superior matched care to be delivered. Personalized medicine does not merely
      refer to the incorporation of genetic information into clinical care, it involves
      utilization of the wide array of data points relevant to care, many of which are
      readily available at the bedside today. By pushing uptake of personalized
      matching available today, clinicians can better address the triple aim of
      improved health, lowers costs, and enhanced patient experience, and we can
      prepare the health care landscape for the iterative inclusion of progressively
      more sophisticated information as newer tests and information become available to
      support the personalized medicine paradigm. 

PMID- 25562409
TI  - Sensors: views of staff of a disability service organization.
AB  - Sensors have become ubiquitous in their reach and scope of application. They are
      a technological cornerstone for various modes of health surveillance and
      participatory medicine-such as quantifying oneself; they are also employed to
      track people with certain as impairments perceived ability differences. This
      paper presents quantitative and qualitative data of an exploratory, non
      generalizable study into the perceptions, attitudes and concerns of staff of a
      disability service organization, that mostly serve people with intellectual
      disabilities, towards the use of various types of sensor technologies that might
      be used by and with their clients. In addition, perspectives of various types of
      privacy issues linked to sensors, as well data regarding the concept of
      quantified self were obtained. Our results highlight the need to involve disabled
      people and their support networks in sensor and quantified-self discourses, in
      order to prevent undue disadvantages. 

PMID- 25562408
TI  - Driving forces behind the past and future emergence of personalized medicine.
AB  - Personalized medicine can be seen as a continuously developing approach to
      tailoring treatments according to the individual characteristics of a patient. In
      some way, medicine has always been personalized. During the last decade, however,
      scientific and technological progress have made truly personalized healthcare
      increasingly become reality. Today's personalized medicine involves targeted
      therapies and diagnostic tests. The development of targeted agents represents a
      major investment opportunity to pharmaceutical companies, which have been facing
      the need to diversify their business due to an increasingly challenging market
      place. By investing into the development of personalized therapies,
      pharmaceutical companies mitigate a major part of the risks posed by factors such
      as patent expiries or generic competition. Viewing upon personalized medicine
      from different perspectives points out the multi-causality of its emergence.
      Research efforts and business diversification have been two main driving forces;
      they do supplement each other, however, are not jointly exhaustive in explaining
      the emergence of this approach. Especially in the future, a number of further
      stakeholders will impact the evolution of personalized medicine. 

PMID- 25562410
TI  - Laterality, spatial abilities, and accident proneness.
AB  - Although handedness as a measure of cerebral specialization has been linked to
      accident proneness, more direct measures of laterality are rarely considered. The
      present study aimed to fill that gap in the existing research. In addition,
      individual difference factors in accident proneness were further examined with
      the inclusion of mental rotation and navigation abilities measures. One hundred
      and forty participants were asked to complete the Mental Rotations Test, the
      Santa Barbara Sense of Direction scale, the Greyscales task, the Fused Dichotic
      Word Test, the Waterloo Handedness Questionnaire, and a grip strength task before
      answering questions related to number of accidents in five areas. Results
      indicated that handedness scores, absolute visual laterality score, absolute
      response time on the auditory laterality index, and navigation ability were
      significant predictors of the total number of accidents. Results are discussed
      with respect to cerebral hemispheric specialization and risk-taking attitudes and
      behavior. 

PMID- 25562411
TI  - Band engineering in core/shell ZnTe/CdSe for photovoltage and efficiency
      enhancement in exciplex quantum dot sensitized solar cells.
AB  - Even though previously reported CdTe/CdSe type-II core/shell QD sensitizers
      possess intrinsic superior optoelectronic properties (such as wide absorption
      range, fast charge separation, and slow charge recombination) in serving as light
      absorbers, the efficiency of the resultant solar cell is still limited by the
      relatively low photovoltage. To further enhance photovoltage and cell efficiency
      accordingly, ZnTe/CdSe type-II core/shell QDs with much larger conduction band
      (CB) offset in comparison with that of CdTe/CdSe (1.22 eV vs 0.27 eV) are adopted
      as sensitizers in the construction of quantum dot sensitized solar cells (QDSCs).
      The augment of band offset produces an increase of the charge accumulation across
      the QD/TiO2 interface under illumination and induces stronger dipole effects,
      therefore bringing forward an upward shift of the TiO2 CB edge after
      sensitization and resulting in enhancement of the photovoltage of the resultant
      cell devices. The variation of relative chemical capacitance, CMU, between
      ZnTe/CdSe and reference CdTe/CdSe cells extracted from impedance spectroscopy
      (IS) characterization under dark and illumination conditions clearly demonstrates
      that, under light irradiation conditions, the sensitization of ZnTe/CdSe QDs
      upshifts the CB edge of TiO2 by the level of ~ 50 mV related to that in the
      reference cell and results in the enhancement of V(oc) of the corresponding cell
      devices. In addition, charge extraction measurements have also confirmed the
      photovoltage enhancement in the ZnTe/CdSe cell related to reference CdTe/CdSe
      cell. Furthermore, transient grating (TG) measurements have revealed a faster
      electron injection rate for the ZnTe/CdSe-based QDSCs in comparison with the CdSe
      cells. The resultant ZnTe/CdSe QD-based QDSCs exhibit a champion power conversion
      efficiency of 7.17% and a certified efficiency of 6.82% under AM 1.5 G full one
      sun illumination, which is, as far as we know, one of the highest efficiencies
      for liquid-junction QDSCs.

PMID- 25562412
TI  - Gender inequality and the risk of HIV among married couples in North India.
AB  - This study investigated the distribution and determinants of HIV risks among
      married couples in North India. Gender inequality emerged as a potential driver
      of HIV risks in this region. Data collection took place in 2003 in a probability
      survey of 3385 couples living in India's most populous state - Uttar Pradesh -
      and Uttaranchal. Couples' analyses utilizing generalized estimating equations
      showed that compared with husbands, wives were less knowledgeable about HIV (OR =
      0.31, 95% CI = 0.27-0.36), more likely to consider themselves at risk for
      infection (OR = 6.86, 95% CI = 4.65-10.13), and less likely to feel that a wife
      had the right to refuse sex with her husband (OR = 0.50, 95% CI = 0.44-0.58). The
      proportion of husbands reporting non-marital sex in the past year was 7.1% and
      transactional sex in the past year, 2.2%. Among their wives, 73.4% were unaware
      of their husbands' non-marital sexual behaviors and only 28.9% of husbands
      reported condom use during their last non-marital sexual encounter. Logistic
      regression analyses showed that husbands' alcohol use, husbands' mobility, and
      urban residence were positively associated with husbands' non-marital sexual
      behaviors adjusting for other covariates. The data demonstrate that HIV
      prevention programs among couples in North India should consider both sexual
      risks and gender inequalities which potentially fuel HIV spread in this region. 

PMID- 25562414
TI  - SOX10 expression in a gangliocytic paraganglioma--a case report.
AB  - We present a case of a 49-year-old woman who underwent a pancreaticoduodenectomy
      for symptomatic treatment of an obstructive periampullary duodenal mass initially
      found on CT imaging. Histologically, the tumor showed a triphasic pattern
      including small round cells, a spindle-cell component and ganglion cells of
      varying size. Furthermore, the tumor was surrounded by a proliferation of
      pancreatic ducts. These features led to the diagnosis of a gangliocytic
      paraganglioma arising in an ectopic pancreas. Sections of the tumor were then
      stained for SOX10, a neural crest transcription factor, and it was shown to be
      positive in the ganglion cells. The exact origin of gangliocytic paragangliomas
      has not yet been clearly defined. However, this finding of aberrant expression of
      SOX10 supports the idea of these lesions being neoplastic in nature. 

PMID- 25562416
TI  - Depressive thoughts limit working memory capacity in dysphoria.
AB  - Dysphoria is associated with persistence of attention on mood-congruent
      information. Longer time attending to mood-congruent information for dysphoric
      individuals (DIs) detracts from goal-relevant information processing and should
      reduce working memory (WM) capacity. Study 1 showed that DIs and non-DIs have
      similar WM capacities. Study 2 embedded depressive information into a WM task.
      Compared to non-DIs, DIs showed significantly reduced WM capacity for goal
      relevant information in this task. Study 3 replicated results from Studies 1 and
      2, and further showed that DIs had a significantly greater association between
      processing speed and recall on the depressively modified WM task compared to non
      DIs. The presence of inter-task depressive information leads to DI-related
      decreased WM capacity. Results suggest dysphoria-related WM capacity deficits
      when depressive thoughts are present. WM capacity deficits in the presence of
      depressive thoughts are a plausible mechanism to explain day-to-day memory and
      concentration difficulties associated with depressed mood. 

PMID- 25562415
TI  - Development and validation of the JAX Cancer Treatment ProfileTM for detection of
      clinically actionable mutations in solid tumors.
AB  - BACKGROUND: The continued development of targeted therapeutics for cancer
      treatment has required the concomitant development of more expansive methods for
      the molecular profiling of the patient's tumor. We describe the validation of the
      JAX Cancer Treatment ProfileTM (JAX-CTPTM), a next generation sequencing (NGS)
      based molecular diagnostic assay that detects actionable mutations in solid
      tumors to inform the selection of targeted therapeutics for cancer treatment.
      METHODS: NGS libraries are generated from DNA extracted from formalin fixed
      paraffin embedded tumors. Using hybrid capture, the genes of interest are
      enriched and sequenced on the Illumina HiSeq 2500 or MiSeq sequencers followed by
      variant detection and functional and clinical annotation for the generation of a
      clinical report. RESULTS: The JAX-CTPTM detects actionable variants, in the form
      of single nucleotide variations and small insertions and deletions (<=50 bp) in
      190 genes in specimens with a neoplastic cell content of >=10%. The JAX-CTPTM is
      also validated for the detection of clinically actionable gene amplifications.
      CONCLUSIONS: There is a lack of consensus in the molecular diagnostics field on
      the best method for the validation of NGS-based assays in oncology, thus the
      importance of communicating methods, as contained in this report. The growing
      number of targeted therapeutics and the complexity of the tumor genome
      necessitate continued development and refinement of advanced assays for tumor
      profiling to enable precision cancer treatment.

PMID- 25562417
TI  - SAR-guided development and characterization of a potent antitumor compound toward
      B-cell neoplasms with no detectable cytotoxicity toward healthy cells.
AB  - Acute hematological diseases (leukemias and aggressive lymphomas) can be cured in
      approximately half of the patients, while the other patients die from their
      disease. Chronic leukemias and indolent lymphomas can be well controlled for
      years in most cases. However, the cure rate of these patients is low and the
      course of the disease is characterized by frequent recurrence. Therefore, novel
      agents for monotherapies or combination therapies still need to be explored. The
      presented study describes the identification of the chalcone derivative 15 on
      different types of human malignant cells of the lymphoid and myeloid lineage.
      Further experiments performed with compound 15 on peripheral blood mononuclear
      cells (PBMCs) of chronic lymphocytic leukemia (CLL) patients clearly stated a
      higher cytotoxicity in PBMC from CLL patients compared to healthy donors (HD).
      The newly identified chalcone derivative 15 showed a higher therapeutic potential
      than fludarabine, a drug already in use in lymphoma treatment. 

PMID- 25562418
TI  - High-resolution 400K oligonucleotide array comparative genomic hybridization
      analysis of neurofibromatosis type 1-associated cutaneous neurofibromas.
AB  - Neurofibromatosis type 1 (NF1) is a genetic disorder where affected individuals
      develop benign or malignant nervous system tumors. To date, NF1 is caused by
      mutations in the NF1 tumor suppressor gene located at chromosome band 17q11.2. In
      this study, we aimed to characterize novel recurrent regional chromosomal
      imbalances and tumor-related candidate genes in NF1-associated cutaneous
      neurofibromas. Nine cutaneous neurofibromas from NF1 patients were screened for
      recurrent chromosomal imbalances using high-resolution 400K oligonucleotide array
      comparative genomic hybridization (aCGH). All the cases exhibited at least one
      sub-microscopic abnormality. Regions of recurrent chromosomal imbalances in a
      least one third of cases were loss of 1q13.2 (33%, FAM19A3), 1q21.1 (44%,
      RABGAP1L), 2q37.1 (56%, INPP5D), 3p25.1 (67%, CHCHD4), 4p15.32 (56%, FGFBP1),
      5q11.2 (56%, ARL15), 6q22.31 (56%, NKAIN2), 6q22.33 (67%, ARHGAP18), 6q25.1 (67%,
      UST), 7q13 (56%, ADCY1), 12q13.13 (44%, KRT71), 19q13.32 (56%, GRLF1), and
      20p11.21 (56%, NLP) and gain of 2p23.3 (76%, C2orf53), 8q22.3 (44%, ODF1) and
      8q24.3 (67%, ARC). Several chromosomal imbalances, including loss of 7q11.23,
      13q14.1, 14q32.13, 17p12, and 17q11.2 were detected at a lower frequency. We also
      confirmed that these chromosomal imbalances were not detected in the patient
      matched lymphocyte DNAs. Amongst the 6 tumor-related candidate genes (RABGAP1L,
      ADCY1, SLIT2, GRLF1, UST, and ARC) identified in the regions of recurrent
      chromosomal imbalances, the gene expression changes of UST (down-regulation) and
      ARC (up-regulation) were found to be significantly associated with copy number
      alterations. The novel recurrent chromosomal imbalances and the altered
      expression levels of the tumor-related candidate genes may be associated with the
      development of NF1-associated benign cutaneous neurofibromas.

PMID- 25562419
TI  - On (ab)normality: Einstein's fusiform gyrus.
AB  - Recently, Hines (2014) wrote an evocative paper challenging findings from both
      histological and morphological studies of Einstein's brain. In this discussion
      paper, I extend Hines' theoretical point and further discuss how best to
      determine 'abnormal' morphology. To do so, I assess the sulcal patterning of
      Einstein's fusiform gyrus (FG) for the first time. The sulcal patterning of the
      FG was unconsidered in prior studies because the morphological features of the
      mid-fusiform sulcus have only been clarified recently. On the one hand, the
      sulcal patterning of Einstein's FG is abnormal relative to averages of 'normal'
      brains generated from two independent datasets (N = 39 and N = 15, respectively).
      On the other hand, within the 108 hemispheres used to make these average brains,
      it is not impossible to find FG sulcal patterns that resemble those of Einstein.
      Thus, concluding whether a morphological pattern is normal or abnormal heavily
      depends on the chosen analysis method (e.g. group average vs. individual). Such
      findings question the functional meaning of morphological 'abnormalities' when
      determined by comparing an individual to an average brain or average frequency
      characteristics. These observations are not only important for analyzing a rare
      brain such as that of Einstein, but also for comparing macroanatomical features
      between typical and atypical populations.

PMID- 25562420
TI  - Voltage-gated sodium channel function and expression in injured and uninjured rat
      dorsal root ganglia neurons.
AB  - The nine members of the voltage-gated sodium channel (Nav) family mediate inward
      sodium currents that depolarize neurons and lead to action potential firing.
      Increased Nav expression and function in sensory ganglia may drive ectopic action
      potentials and result in neuropathic pain. Using patch-clamp electrophysiology
      and molecular biology techniques, experiments were performed to elucidate the
      contribution of Nav channels to sodium currents in rat dorsal root ganglion (DRG)
      neurons following the L5/L6 spinal nerve ligation (SNL) model of neuropathic
      pain. The abundance of DRG neurons with fast, tetrodotoxin sensitive (TTX-S)
      currents was seven-fold higher whereas the abundance of DRG neurons with slow,
      tetrodotoxin resistant (TTX-R) currents was nearly thirty-fold lower when
      comparing ipsilateral (injured) to contralateral (uninjured) neurons. TTX-S
      currents were elevated in larger neurons while TTX-R currents were reduced in
      both small and large neurons. Among Nav transcripts encoding TTX-R channels,
      Scn10a (Nav1.8) and Scn11a (Nav1.9) expression was twenty- to thirty-fold lower,
      while among Nav transcripts encoding TTX-S channels, Scn3a (Nav1.3) expression
      was four-fold higher in injured compared to uninjured DRG by qRT-PCR analysis. In
      summary, the SNL model of neuropathic pain induced a phenotypic switch in Nav
      expression from TTX-R to TTX-S channels in injured DRG neurons. Transcriptional
      reprogramming of Nav genes may drive ectopic action potential firing and
      contribute to neuropathic pain. 

PMID- 25562421
TI  - Comparison of osteoclastogenesis and resorption activity of human osteoclasts on
      tissue culture polystyrene and on natural extracellular bone matrix in 2D and 3D.
AB  - Bone homeostasis is maintained by osteoblasts (bone formation) and osteoclasts
      (bone resorption). While there have been numerous studies investigating
      mesenchymal stem cells and their potential to differentiate into osteoblasts as
      well as their interaction with different bone substitute materials, there is only
      limited knowledge concerning in vitro generated osteoclasts. Due to the
      increasing development of degradable bone-grafting materials and the need of
      sophisticated in vitro test methods, it is essential to gain deeper insight into
      the process of osteoclastogenesis and the resorption functionality of human
      osteoclasts. Therefore, we focused on the comparison of osteoclastogenesis and
      resorption activity on tissue culture polystyrene (TCPS) and bovine extracellular
      bone matrices (BMs). Cortical bone slices were used as two-dimensional (2D)
      substrates, whereas a thermally treated cancellous bone matrix was used for three
      dimensional (3D) experiments. We isolated primary human monocytes and induced
      osteoclastogenesis by medium supplementation. Subsequently, the expression of the
      vitronectin receptor (alphaVbeta3) and cathepsin K as well as the characteristic
      actin formation on TCPS and the two BMs were examined. The cell area of human
      osteoclasts was analyzed on TCPS and on BMs, whereas significantly larger
      osteoclasts could be detected on BMs. Additionally, we compared the diameter of
      the sealing zones with the measured diameter of the resorption pits on the BMs
      and revealed similar diameters of the sealing zones and the resorption pits. We
      conclude that using TCPS as culture substrate does not affect the expression of
      osteoclast-specific markers. The analysis of resorption activity can successfully
      be conducted on cortical as well as on cancellous bone matrices. For new in vitro
      test systems concerning bone resorption, we suggest the establishment of a 2D
      assay for high throughput screening of new degradable bone substitute materials
      with osteoclasts. 

PMID- 25562422
TI  - Continuous culture methodology for the screening of microalgae for oil.
AB  - A basic criterion in the selection of microalgae suitable as source of oil for
      biodiesel should be their actual capacity to produce lipids or, more properly,
      the fatty acid yield. Performance assessment of 10 preselected microalgae under
      both batch and continuous culture points to the latter approach as the most
      adequate for evaluating fatty acid productivity. Differences were patent in
      continuous culture among strains that otherwise had analogous oil accumulation
      potential under batch culture. Some promising strains under batch culture (like
      Muriella aurantiaca and Monoraphidium braunii) exhibited, however, values for
      actual fatty acid productivity lower than 40 mgL(-1)d(-1) in continuous regime.
      The analysis performed in photochemostat under continuous culture regime revealed
      the great potential of Chlorococcum olefaciens, Pseudokirchneriella subcapitata
      and Scenedesmus almeriensis as oil producing microalgae. Fatty acid productivity
      levels over 90 mgL(-1)d(-1) were recorded for the latter strains under moderate
      nitrogen limitation, conditions which led to an enrichment in saturated and
      monounsaturated fatty acids, a more suitable profile as raw material for
      biodiesel. The continuous culture methodology employed represents a sound
      procedure for screening microalgae for biofuel production, providing a reliable
      evaluation of their fatty acid production capacity, under conditions close to
      those of outdoor production systems.

PMID- 25562423
TI  - A modular segmented-flow platform for 3D cell cultivation.
AB  - In vitro 3D cell cultivation is promised to equate tissue in vivo more
      realistically than 2D cell cultivation corresponding to cell-cell and cell-matrix
      interactions. Therefore, a scalable 3D cultivation platform was developed. This
      platform, called pipe-based bioreactors (pbb), is based on the segmented-flow
      technology: aqueous droplets are embedded in a water-immiscible carrier fluid.
      The droplet volumes range from 60 nL to 20 MUL and are used as bioreactors lined
      up in a tubing like pearls on a string. The modular automated platform basically
      consists of several modules like a fluid management for a high throughput droplet
      generation for self-assembly or scaffold-based 3D cell cultivation, a storage
      module for incubation and storage, and an analysis module for monitoring cell
      aggregation and proliferation basing on microscopy or photometry. In this report,
      the self-assembly of murine embryonic stem cells (mESCs) to uniformly sized
      embryoid bodies (EBs), the cell proliferation, the cell viability as well as the
      influence on the cell differentiation to cardiomyocytes are described. The
      integration of a dosage module for medium exchange or agent addition will enable
      pbb as long-term 3D cell cultivation system for studying stem cell
      differentiation, e.g. cardiac myogenesis or for diagnostic and therapeutic
      testing in personalized medicine.

PMID- 25562424
TI  - Production and purification of recombinant human hepcidin-25 with authentic N and
      C-termini.
AB  - Hepcidin was first identified as an antimicrobial peptide present in human serum
      and urine. It was later demonstrated that hepcidin is the long-sought hormone
      that regulates iron homeostasis in mammals. Recombinant human Hepcidin-25
      (Hepc25) was expressed in Pichia pastoris using a modified version of the
      pPICZalphaA vector. Hepc25 was then purified by a simple two-step chromatographic
      process to obtain 1.9 mg of soluble recombinant human Hepc25 per liter of culture
      at 96% purity. The sequence of Hepc25 and the presence of four disulfide bridges
      were confirmed by mass spectrometry analyses, and the recombinant Hepc25
      exhibited antibacterial activity. This protocol of production and purification is
      the first step toward the production of human Hepc25 at a greater scale.

PMID- 25562425
TI  - Developmental profile of anthocyanin, flavonol, and proanthocyanidin type,
      content, and localization in saskatoon fruits (Amelanchier alnifolia Nutt.).
AB  - Saskatoons (Amelanchier alnifolia Nutt.) are small fruits that contain
      substantial quantities of flavonoids. To further characterize and understand the
      role of these flavonoids during fruit development, anthocyanins, flavonols, and
      proanthocyanidins were identified, quantified, and localized over development in
      cultivars that produce blue-purple or white fruit at maturity. Anthocyanin
      content was low in young fruit and then dramatically increased as the fruit
      transitioned into ripening only in the pigmented-fruit (blue-purple) cultivars.
      Proanthocyanidins with both A-type and B-type linkages were detected in fruit,
      with (-)-epicatechin as the most abundant proanthocyanidin subunit. Flavonol and
      proanthocyanidin content was high in, and localized throughout, the tissues of
      young fruit and in the developing seed coats, with levels decreasing as the fruit
      expanded. Our data show that flavonoid type, content, and tissue localization
      vary throughout development in saskatoon fruit. These data can be used to target
      specific fruit developmental stages and flavonoid classes for optimization of
      health-beneficial flavonoid content. 

PMID- 25562426
TI  - PKCdelta-iPLA2-PGE2-PPARgamma signaling cascade mediates TNF-alpha induced
      Claudin 1 expression in human lung carcinoma cells.
AB  - Claudin 1 (CLDN1) is a critical component of tight junction adhesion complexes
      that maintains the structural integrity of epithelial cell layers. Dysregulation
      of CLDN1 is associated with the growth and metastasis of human lung
      adenocarcinoma. TNF-alpha treatment was previously shown to increase expression
      of CLDN1 that mediated lung cancer cell morphology changes and migration. This
      study aimed to elucidate the molecular mechanisms involved in TNF-alpha induced
      CLDN1 expression in human lung carcinoma A549 cells. Chemical inhibition or siRNA
      downregulation of Src, PI3K, Akt, MAPKs, NFkappaB, caspase and PKC demonstrated
      that PKC, specifically PKCdelta, is required for TNF-alpha induced CLDN1
      expression. Further investigation of the PKC pathway revealed that CLDN1
      expression is enhanced by the downstream molecules iPLA2, PGE2, 15-keto PGE2 and
      PPARgamma. Conversely, inhibition of these molecules decreased CLDN1 expression.
      Additionally, a wound-healing assay demonstrated that TNF-alpha stimulation, PKC
      activation, prostaglandin treatment or PPARgamma activation enhanced cell
      migration. In conclusion, TNF-alpha induced CLDN1 expression is regulated by the
      PKCdelta-iPLA2-PGE2-PPARgamma signaling cascade in human lung carcinoma A549
      cells. 

PMID- 25562427
TI  - Signaling pathway for adiponectin expression in adipocytes by osteocalcin.
AB  - In addition to providing skeletal support, the bone is an endocrine organ that
      produces osteocalcin, whose uncarboxylated form (GluOC) increases insulin
      secretion either directly or indirectly by promoting incretin secretion. We have
      now investigated the signaling pathway by which GluOC increases expression of
      adiponectin in adipocytes. Activation of its putative receptor GPRC6A by GluOC
      induced the intracellular accumulation of cAMP and consequent activation of
      protein kinase A (PKA) in differentiated 3T3-L1 adipocytes. It also induced
      phosphorylation of CREB (cAMP response element binding protein), but this effect
      appeared to be mediated indirectly by extracellular signal-regulated kinase (ERK)
      rather than directly by PKA, given that it was attenuated by the ERK signaling
      inhibitor U0126. Activated PKA also induced activation of the tyrosine kinase
      Src, the small GTPase Rap1, an upstream of ERK and CREB phosphorylation.
      Activated CREB up-regulated the expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma), which in turn led to induction of adiponectin
      expression. Finally, intermittent oral administration of GluOC in mice reduced
      the size of gonadal white adipocytes as well as increased the expression of
      PPARgamma and adiponectin in these cells. Our results have thus revealed the
      signaling pathway by which GluOC induces adiponectin expression in adipocytes. 

PMID- 25562428
TI  - PDZK1/NHERF3 differentially regulates corticotropin-releasing factor receptor 1
      and serotonin 2A receptor signaling and endocytosis.
AB  - The corticotropin-releasing factor receptor 1 (CRFR1) and serotonin 2A receptor
      (5-HT2AR) are linked to cellular mechanisms underlying stress anxiety and
      depression. Both receptors are members of the G protein-coupled receptor (GPCR)
      superfamily and encode class I PSD-95/DiscsLarge/Zona Occludens 1 (PDZ) binding
      motifs (-S/T-x-V/I/L) at the end of their carboxyl-terminal tails. We have
      identified PDZK1, also referred to as Na(+)/H(+) exchange regulatory cofactor 3
      (NHERF3) as both a CRFR1- and 5-HT2AR-interacting protein. We have examined
      whether PDZK1 plays a role in regulating both CRFR1 and 5-HT2AR activity. We find
      that while PDZK1 interactions with CRFR1 are PDZ binding motif-dependent, PDZK1
      associates with 5-HT2AR in a PDZ binding motif-independent manner and CRFR1
      expression, but not 5-HT2AR expression, redistributes PDZK1 to the plasma
      membrane in PDZ binding motif-dependent manner. PDZK1, negatively regulates 5
      HT2AR endocytosis and has no effect upon 5-HT2AR-mediated ERK1/2 phosphorylation.
      In contrast, PDZK1 overexpression does not affect CRFR1 endocytosis, but
      selectively increases CRFR1-stimulated ERK1/2 phosphorylation. Similar to what
      has been previously reported for PSD-95 and SAP97, PDZK1 positively influences 5
      HT2AR-stimulated inositol phosphate formation, but does not contribute to the
      regulation of CRFR1-mediated cAMP signaling. Taken together, these results
      indicate that PDZK1 differentially regulates the signaling and trafficking of
      CRFR1 and 5-HT2AR via PDZ-dependent and -independent mechanisms, respectively.

PMID- 25562429
TI  - Phospho-STIM1 is a downstream effector that mediates the signaling triggered by
      IGF-1 in HEK293 cells.
AB  - STIM1 is a Ca(2+) sensor of the endoplasmic reticulum (ER) that triggers the
      activation of plasma membrane Ca(2+) channels upon depletion of Ca(2+) levels
      within the ER. During thapsigargin-triggered Ca(2+) store depletion, ERK1/2
      phosphorylates STIM1 at Ser575, Ser608, and Ser621. This phosphorylation plays a
      role in the regulation of STIM1 dissociation from the microtubule plus-end
      binding protein EB1, an essential step for STIM1 activation by thapsigargin.
      However, little is known regarding the physiological role of this
      phosphorylation. Because IGF-1 triggers the activation of the RAF-MEK-ERK and the
      phosphoinositide pathways, the role of STIM1 phosphorylation in IGF-1 stimulation
      was studied. There was found to be phosphorylation of ERK1/2 in both the presence
      and the absence of extracellular Ca(2+), demonstrating that Ca(2+) influx is not
      essential for ERK1/2 activation. In parallel, IGF-1 triggered STIM1
      phosphorylation at the aforementioned sites, an effect that was blocked by
      PD0325901, a MEK1/2 inhibitor used to block ERK1/2 activation. Also, STIM1-GFP
      was found in clusters upon IGF-1 stimulation, and STIM1-S575A/S608A/S621A-GFP
      strongly reduced this multimerization. Interestingly, phospho-STIM1 was mainly
      found in clusters when cells were treated with IGF-1, and IGF-1 triggered the
      dissociation of STIM1 from EB1, similarly to what has been observed for
      thapsigargin, suggesting that STIM1 mediates the IGF-1 signaling pathway. A study
      of IGF-1-stimulated NFAT translocation was therefore performed, finding that
      STIM1-S575A/S608A/S621A blocked this translocation, as did the fusion protein
      STIM1-EB1, confirming that both STIM1 phosphorylation and STIM1-EB1 dissociation
      are required for IGF-1-triggered Ca(2+)-dependent signaling, and demonstrating
      that STIM1 phosphorylation plays a role as a downstream effector of the RAF-MEK
      ERK pathway and an upstream activator of Ca(2+) entry. 

PMID- 25562430
TI  - Oncostatin M regulates SOCS3 mRNA stability via the MEK-ERK1/2-pathway
      independent of p38(MAPK)/MK2.
AB  - The induction of suppressor of cytokine signalling (SOCS)3 expression context
      dependently involves regulation of SOCS3 transcript stability as previously
      demonstrated for MAPK activated protein kinase (MK)2-dependent regulation of
      SOCS3 expression by TNFalpha (Ehlting et al., 2007). In how far the IL-6-type
      cytokine OSM, which in contrast to IL-6 is a strong activator of p38(MAPK)/MK2
      signalling, also involves regulation of transcript stability and activation of
      MK2 to induce SOCS3 expression is unclear. In contrast to IL-6, OSM induces SOCS3
      expression in murine fibroblasts and in primary human and murine hepatocytes, but
      not in macrophages because the latter lack the OSM receptor (OSMR)beta subunit.
      Evidence is provided that regulation of OSM-induced expression of SOCS3 involves
      MEK1- and Erk1/2-mediated stabilization of the SOCS3 transcript. Consistently,
      OSM-induced stabilization of the SOCS3 transcript is impaired in the presence of
      inhibitors that specifically block activation of MEK1/2 (U0126) and ERK1/2
      (FR180204) or upon knock-down of ERK1/2 expression using specific siRNA. As a
      potential target site that integrates the stability regulating effect of OSM and
      OSM-induced activation of MEK1/2 and ERK1/2 a region containing three copies of a
      pentameric AUUUA motif located within position 2422 and 2541 in closed proximity
      to the 3' UTR of the SOCS3 transcript has been identified. Unexpectedly,
      activation of the p38(MAPK)/MK2 pathway, which apart from STAT3 and ERK1/2, is
      also strongly activated by OSM in human and murine hepatocytes and murine
      fibroblasts is dispensable for stabilization of the SOCS3 transcript as suggested
      from inhibitor studies using the p38(MAPK) inhibitor SB203580 or from the
      analysis of MK2-deficient hepatocytes. However, analysis of MK2-deficient
      macrophages and hepatocytes revealed that, although MK2 is dispensable for
      regulation of OSM-induced SOCS3 expression, MK2 is essential for LPS-induced OSM
      production in macrophages and limits the overall availability of the OSMRbeta
      subunit in hepatocytes. Thus MK2 plays a role for the induction and sensing of
      OSM-mediated intercellular signalling between macrophages and hepatocytes during
      LPS-induced inflammation.

PMID- 25562431
TI  - Methane to acetic acid over Cu-exchanged zeolites: mechanistic insights from a
      site-specific carbonylation reaction.
AB  - The selective low temperature oxidation of methane is an attractive yet
      challenging pathway to convert abundant natural gas into value added chemicals.
      Copper-exchanged ZSM-5 and mordenite (MOR) zeolites have received attention due
      to their ability to oxidize methane into methanol using molecular oxygen. In this
      work, the conversion of methane into acetic acid is demonstrated using Cu-MOR by
      coupling oxidation with carbonylation reactions. The carbonylation reaction,
      known to occur predominantly in the 8-membered ring (8MR) pockets of MOR, is used
      as a site-specific probe to gain insight into important mechanistic differences
      existing between Cu-MOR and Cu-ZSM-5 during methane oxidation. For the tandem
      reaction sequence, Cu-MOR generated drastically higher amounts of acetic acid
      when compared to Cu-ZSM-5 (22 vs 4 MUmol/g). Preferential titration with sodium
      showed a direct correlation between the number of acid sites in the 8MR pockets
      in MOR and acetic acid yield, indicating that methoxy species present in the MOR
      side pockets undergo carbonylation. Coupled spectroscopic and reactivity
      measurements were used to identify the genesis of the oxidation sites and to
      validate the migration of methoxy species from the oxidation site to the
      carbonylation site. Our results indicate that the Cu(II)-O-Cu(II) sites
      previously associated with methane oxidation in both Cu-MOR and Cu-ZSM-5 are
      oxidation active but carbonylation inactive. In turn, combined UV-vis and EPR
      spectroscopic studies showed that a novel Cu(2+) site is formed at Cu/Al <0.2 in
      MOR. These sites oxidize methane and promote the migration of the product to a
      Bronsted acid site in the 8MR to undergo carbonylation. 

PMID- 25562432
TI  - Transparent reporting of a multivariable prediction model for individual
      prognosis or diagnosis (TRIPOD): the TRIPOD statement.
AB  - Prediction models are developed to aid health-care providers in estimating the
      probability or risk that a specific disease or condition is present (diagnostic
      models) or that a specific event will occur in the future (prognostic models), to
      inform their decision making. However, the overwhelming evidence shows that the
      quality of reporting of prediction model studies is poor. Only with full and
      clear reporting of information on all aspects of a prediction model can risk of
      bias and potential usefulness of prediction models be adequately assessed. The
      Transparent Reporting of a multivariable prediction model for Individual
      Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for
      the reporting of studies developing, validating, or updating a prediction model,
      whether for diagnostic or prognostic purposes. This article describes how the
      TRIPOD Statement was developed. An extensive list of items based on a review of
      the literature was created, which was reduced after a Web-based survey and
      revised during a 3-day meeting in June 2011 with methodologists, health-care
      professionals, and journal editors. The list was refined during several meetings
      of the steering group and in e-mail discussions with the wider group of TRIPOD
      contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed
      essential for transparent reporting of a prediction model study. The TRIPOD
      Statement aims to improve the transparency of the reporting of a prediction model
      study regardless of the study methods used. The TRIPOD Statement is best used in
      conjunction with the TRIPOD explanation and elaboration document. To aid the
      editorial process and readers of prediction model studies, it is recommended that
      authors include a completed checklist in their submission (also available at
      www.tripod-statement.org). 

PMID- 25562433
TI  - Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma
      and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways.
AB  - BACKGROUND: Myxoid liposarcoma (MLS) is the second most common subtype of
      liposarcoma, and metastasis occurs in up to one-third of cases. However, the
      mechanisms of invasion and metastasis remain unclear. Tumour-associated
      macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or
      poor prognosis. The aim of this study was to investigate the relationship between
      TAMs and MLS. METHODS: Using 78 primary MLS samples, the association between
      clinical prognosis and macrophage infiltration was evaluated by immunochemistry.
      The effects of macrophages on cell growth, cell motility, and invasion of MLS
      cell lines were investigated in vitro. In addition, clinicopathological factors
      were analysed to assess their prognostic implications in MLS. RESULTS: Higher
      levels of CD68-positive macrophages were associated with poorer overall survival
      in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and
      invasion by activating epidermal growth factor receptor (EGFR), with the key
      ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The
      phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell
      motility and invasion of MLS. The expression of phosphorylated EGFR in MLS
      clinical samples was associated with macrophage infiltration. In addition, more
      significant macrophage infiltration was associated with poor prognosis even in
      multivariate analysis. CONCLUSIONS: Macrophage infiltration in MLS predicts poor
      prognosis, and the relationship between TAMs and MLS may be a new candidate for
      therapeutic targets of MLS.

PMID- 25562435
TI  - Prognostic value of circulating tumour cells for early recurrence after resection
      of colorectal liver metastases.
AB  - BACKGROUND: Despite good outcomes for many, a substantial group of patients
      undergoing metastasectomy for isolated liver metastases from colorectal cancer
      (CRC) experience early recurrence. We have investigated whether circulating
      tumour cell (CTC) detection can identify patients developing disease recurrence
      within 1 year after liver metastasectomy. METHODS: In CRC patients undergoing
      liver metastasectomy, 30 ml peripheral blood was withdrawn preoperatively. CTCs
      were detected by the CellSearch system after a density-gradient-based enrichment
      step. RESULTS: One hundred and seventy-three samples from 151 individual patients
      were analysed. In 75 samples (43%), CTCs were detected, 16% had ?3 CTCs/7.5 ml of
      blood. Eighty-two patients (47%) experienced early disease recurrence (<1 year).
      The 1-year recurrence rate between patients with or without detectable CTCs were
      similar (47% vs 48%) or with a low or high CTC count (<3 or ?3 CTCs/7.5 ml of
      blood) (50% vs 47%). Also disease-free and overall survival were similar between
      patients with or without CTCs. CONCLUSIONS: The presence of CTCs in preoperative
      peripheral blood samples does not identify patients at risk for early disease
      recurrence after curative resection of colorectal liver metastases. Other
      parameters are needed to better identify patients at high risk to relapse after
      liver metastasectomy for CRC.

PMID- 25562437
TI  - Circulating leukocyte telomere length and risk of overall and aggressive prostate
      cancer.
AB  - BACKGROUND: Recent large-scale prospective studies suggest that long telomeres
      are associated with an increase cancer risk, counter to conventional wisdom.
      METHODS: To further clarify the association between leukocyte telomere length
      (LTL) and prostate cancer, and assess genetic variability in relation to both LTL
      and prostate cancer, we performed a nested case-control study (922 cases and 935
      controls). The participants provided blood in 1993-1995 and were followed through
      August 2004 (prostate cancer incidence) or until 28 February 2013 (lethal or
      fatal prostate cancer). Relative LTL was measured by quantitative PCR and was
      calculated as the ratio of telomere repeat copy number to a single gene (36B4)
      copy number (T/S). Genotyping was performed using the TaqMan OpenArray SNP
      Genotyping Platform. Logistic regression was used to estimate odds ratios (ORs)
      and 95% confidence intervals (CIs) of all prostate cancer and subtypes defined by
      Gleason grade, stage and lethality (metastasis or death). RESULTS: We observed a
      positive association between each s.d. increase in LTL and all (multivariable
      adjusted OR 1.11, 95% CI: 1.01-1.22), low-grade (OR 1.13, 95% CI:1.01-1.27), and
      localised (OR 1.12, 95% CI:1.01-1.24) prostate cancer. Associations for other
      subtypes were similar, but did not reach statistical significance. In subgroup
      analyses, associations for high grade and advanced stage (OR=2.04, 95% CI 1.00
      4.17; Pinteraction=0.06) or lethal disease (OR=2.37, 95% CI 1.19-4.72;
      Pinteraction=0.01) were stronger in men with a family history of the disease
      compared with those without. The minor allele of SNP, rs7726159, which has
      previously been shown to be positively associated with LTL, showed an inverse
      association with all prostate cancer risk after correction for multiple testing
      (P=0.0005). CONCLUSION: In this prospective study, longer LTL was modestly
      associated with higher risk of prostate cancer. A stronger association for more
      aggressive cancer in men with a family history of the disease needs to be
      confirmed in larger studies.

PMID- 25562434
TI  - Surgical staging and prognosis in serous borderline ovarian tumours (BOT): a
      subanalysis of the AGO ROBOT study.
AB  - BACKGROUND: Incomplete surgical staging is a negative prognostic factor for
      patients with borderline ovarian tumours (BOT). However, little is known about
      the prognostic impact of each individual staging procedure. METHODS: Clinical
      parameters of 950 patients with BOT (confirmed by central reference pathology)
      treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559
      patients with serous BOT and adequate ovarian surgery, further recommended
      staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated
      applying Cox regression models with respect to progression-free survival (PFS).
      RESULTS: For patients with one missing staging procedure, the hazard ratio (HR)
      for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with
      each additional procedure skipped reaching statistical significance in case of
      two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI
      1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a
      statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI
      1.15-3.19; P=0.013) adjusting for previously established prognostic factors as
      FIGO stage, tumour residuals, and fertility preservation. CONCLUSION: Individual
      surgical staging procedures contribute to the prognosis for patients with serous
      BOT. In this analysis, recurrence risk increased with each skipped surgical step.
      This should be considered when re-staging procedures following incomplete primary
      surgery are discussed.

PMID- 25562436
TI  - Childhood body mass index in relation to future risk of oesophageal
      adenocarcinoma.
AB  - BACKGROUND: Middle-aged obese adults are at substantially elevated risk of
      oesophageal adenocarcinoma. It is unclear whether this risk originates earlier in
      life. METHODS: We assessed associations between childhood body mass index (BMI)
      and height-measured annually between ages 7 and 13-with adult oesophageal
      adenocarcinoma in a cohort from the Copenhagen School Health Records Register.
      Analyses included 255 053 children born during 1930-1971. Danish Cancer Registry
      linkage provided outcomes. We calculated hazard ratios (HRs) and 95% confidence
      intervals (CIs) using Cox proportional hazards regression. RESULTS: During 5.4
      million person-years of follow-up, 254 (216 males) incident oesophageal
      adenocarcinomas occurred. At each examined age, cancer risk increased linearly
      per unit BMI z-score, although associations were only statistically significant
      for ages 9-13. The HR for the age of 13 years was 1.31 (95% CI: 1.13, 1.51) per
      unit BMI z-score. Associations were similar in men and women and across birth
      cohorts. Childhood height was not related to cancer risk in men but was in women,
      although these analyses included just 38 female cases. HRs per unit height z
      score at the age of 13 years were 1.04 (0.90, 1.19) in males and 1.77 (1.27,
      2.47) in females, with similar results observed at the other examined ages.
      CONCLUSION: Individuals with higher childhood BMI were at elevated risk of
      oesophageal adenocarcinoma, even though these cancers occurred many decades later
      in life. Although the mechanisms require further investigation, our findings
      provide additional evidence for the long-term health risks of childhood obesity.

PMID- 25562439
TI  - Clinical signs suggestive of pharyngeal dysphagia in preschool children with
      cerebral palsy.
AB  - This study aimed to determine the discriminative validity, reproducibility, and
      prevalence of clinical signs suggestive of pharyngeal dysphagia according to
      gross motor function in children with cerebral palsy (CP). It was a cross
      sectional population-based study of 130 children diagnosed with CP at 18-36
      months (mean=27.4, 81 males) and 40 children with typical development (TD,
      mean=26.2, 18 males). Sixteen signs suggestive of pharyngeal phase impairment
      were directly observed in a videoed mealtime by a speech pathologist, and
      reported by parents on a questionnaire. Gross motor function was classified using
      the Gross Motor Function Classification System. The study found that 67.7% of
      children had clinical signs, and this increased with poorer gross motor function
      (OR=1.7, p<0.01). Parents reported clinical signs in 46.2% of children, with 60%
      agreement with direct clinical mealtime assessment (kappa=0.2, p<0.01). The most
      common signs on direct assessment were coughing (44.7%), multiple swallows
      (25.2%), gurgly voice (20.3%), wet breathing (18.7%) and gagging (11.4%). 37.5%
      of children with TD had clinical signs, mostly observed on fluids. Dysphagia cut
      points were modified to exclude a single cough on fluids, with a modified
      prevalence estimate proposed as 50.8%. Clinical signs suggestive of pharyngeal
      dysphagia are common in children with CP, even those with ambulatory CP. Parent
      report on 16 specific signs remains a feasible screening method. While coughing
      was consistently identified by clinicians, it may not reflect children's regular
      performance, and was not sufficiently discriminative in children aged 18-36
      months. 

PMID- 25562438
TI  - Dual targeting of Angiopoetin-2 and VEGF potentiates effective vascular
      normalisation without inducing empty basement membrane sleeves in xenograft
      tumours.
AB  - BACKGROUND: Effective vascular normalisation following vascular endothelial
      growth factor (VEGF) inhibition is associated with endothelial cell regression
      leaving empty basement membrane sleeves (BMS). These long-lived BMS permit the
      rapid regrowth of tumour vasculature upon treatment cessation and promote
      resistance to VEGF-targeting drugs. Previous attempts at removing BMS have
      failed. Angiopoietin-2 (Ang2) is a vascular destabilizing factor that antagonises
      normalisation. We hypothesised that Ang2 inhibition could permit vascular
      normalisation at significantly reduced doses of VEGF inhibition, avoiding
      excessive vessel regression and the formation of empty BMS. METHODS: Mice
      xenografted with human colorectal cancer cells (LS174T) were treated with low
      (0.5 mg kg(-1)) or high (5 mg kg(-1)) doses of the VEGF-targeting antibody
      bevacizumab with or without an Ang2 blocking peptibody L1-10. Tumour growth, BMS
      formation and normalisation parameters were examined including vessel density,
      pericyte coverage, adherence junctions, leakiness, perfusion, hypoxia and
      proliferation. RESULTS: Dual targeting of VEGF and Ang2 achieved effective
      normalisation at only one-tenth of the dose required with bevacizumab alone.
      Pericyte coverage, vascular integrity, adherence junctions and perfusion as
      prerequisites for improved access of chemotherapy were improved without inducing
      empty BMS that facilitate rapid vascular regrowth. CONCLUSIONS: Dual targeting of
      VEGF and Ang2 can potentiate the effectiveness of VEGF inhibitors and avoid the
      formation of empty BMS.

PMID- 25562440
TI  - Simulating the antimicrobial mechanism of human beta-defensin-3 with coarse
      grained molecular dynamics.
AB  - Human beta-defensin-3 (HbetaD-3) is an endogenous antimicrobial peptide with
      potent and broad killing activity against various microorganisms, and thus, it is
      an attractive candidate for the development of novel peptide antibiotics, but its
      antimicrobial mechanism remains elusive. To characterize the mechanism, we used
      multi-microsecond coarse-grained simulations with the MARTINI force field. These
      simulations show HbetaD-3 peptides can form oligomers on the surface of bacterial
      membrane and make anionic lipids (POPG) clustered. Furthermore, two kinds of
      regions (one is composed of pure POPG lipids, and the other is enriched in POPE
      lipids) are formed in the membrane; on the border of them, there are some obvious
      defects, which result in the membrane disruption. By contrast, the simulations
      also reveal that the contacts between the HbetaD-3 peptides and mammalian
      membrane are not stable. These results provide biophysical insights into HbetaD-3
      selectivity and suggest a possible antimicrobial mechanism. 

PMID- 25562441
TI  - Improving yield and performance in ZnO thin-film transistors made using selective
      area deposition.
AB  - We describe improvements in both yield and performance for thin-film transistors
      (TFTs) fabricated by spatial atomic layer deposition (SALD). These improvements
      are shown to be critical in forming high-quality devices using selective area
      deposition (SAD) as the patterning method. Selective area deposition occurs when
      the precursors for the deposition are prevented from reacting with some areas of
      the substrate surface. Controlling individual layer quality and the interfaces
      between layers is essential for obtaining good-quality thin-film transistors and
      capacitors. The integrity of the gate insulator layer is particularly critical,
      and we describe a method for forming a multilayer dielectric using an oxygen
      plasma treatment between layers that improves crossover yield. We also describe a
      method to achieve improved mobility at the important interface between the
      semiconductor and the gate insulator by, conversely, avoiding oxygen plasma
      treatment. Integration of the best designs results in wide design flexibility,
      transistors with mobility above 15 cm(2)/(V s), and good yield of circuits. 

PMID- 25562442
TI  - Study of low doses cisplatin synergistic effect on photodynamic outcome of
      aluminum phythalocyanine on soft tissue sarcoma (RD) cell line.
AB  - Photodynamic therapy (PDT) in combination with other treatment modality expects
      to overcome the drug resistance experienced in monotherapy. In this present work
      combination of chemo cum PDT is studied over the range of doses. It is found that
      treating cells/exposing cells to chemo drug (cisplatin, CDDP) and PDT
      individually results in minimal cell killing (~7% and ~16%) compared to the
      administration of chemo followed by PDT (~50% cells were viable). These results
      showed that cell viability synergistically decreases in case of combination
      treatment as compared with individual treatment. Photodynamic therapy (PDT) in
      combination with CDDP chemotherapy expects to overcome the drug resistance
      experienced in monotherapy. 

PMID- 25562443
TI  - Structure-activity analysis of human ghrelin O-acyltransferase reveals chemical
      determinants of ghrelin selectivity and acyl group recognition.
AB  - Ghrelin O-acyltransferase (GOAT) is an integral membrane acyltransferase
      responsible for catalyzing a serine-octanoylation posttranslational modification
      within the peptide hormone ghrelin. Ghrelin requires this octanoylation for its
      biological activity in stimulating appetite and in regulating other physiological
      pathways involved in energy balance. Blocking ghrelin acylation using GOAT
      inhibitors is a new potential avenue to treat health conditions impacted by
      ghrelin signaling, such as obesity and diabetes. Designing novel and potent GOAT
      inhibitors as potential therapeutics requires insight into the interactions
      between the ghrelin and octanoyl coenzyme A substrates and the GOAT active site.
      Through structure-activity investigation of ghrelin-mimetic peptide substrates
      and inhibitors, we have analyzed the amino acid selectivity of the enzyme as well
      as the functional groups involved in substrate recognition by human GOAT (hGOAT).
      This analysis reveals that hGOAT both prefers and tolerates a distinct set of
      chemical properties at each position within the N-terminal sequence of ghrelin
      and that sequence elements downstream of the ghrelin N-terminal sequence
      contribute to ghrelin binding to hGOAT. We also found that the hGOAT active site
      exhibits a marked preference for binding an eight-carbon acyl chain, which
      potentially explains the biological observation of ghrelin octanoylation in light
      of the acyl donor promiscuity reported for GOAT. Bioinformatics analysis, guided
      by our reactivity data, supports the conclusion that ghrelin is a unique
      substrate for hGOAT within the human proteome, providing further justification
      for the ghrelin-hGOAT system as a desirable drug target. By defining an array of
      substrate-enzyme interactions used by hGOAT to bind, recognize, and acylate
      ghrelin, this study yields novel insight into the character of the hGOAT active
      site that can serve as a guide toward the rational design of hGOAT inhibitors. 

PMID- 25562444
TI  - Prostate cancer risk estimation tool use by members of the American Urological
      Association: a survey based study.
AB  - PURPOSE: Prostate cancer risk estimation tools have been developed to help guide
      patients and physicians with clinical decision making across all disease states.
      We assessed use patterns of these tools using an online survey sent to AUA
      (American Urological Association) members. MATERIALS AND METHODS: We distributed
      a 21-question online survey to 5,674 AUA members to query prostate cancer risk
      estimation tool use. The survey was divided into 4 categories, including 1)
      demographics, 2) prebiopsy risk assessment, 3) pretreatment risk assessment and
      4) risk estimation tool use. RESULTS: A total of 565 members (10%) responded to
      the online survey, of whom 31% reported using a risk estimation tool in the
      prebiopsy decision setting. Providers who spent more than 20 minutes counseling
      patients were more likely to use a risk estimation tool (OR 2.2, p <0.01). After
      the prostate cancer diagnosis 70% of providers used a risk estimation tools to
      guide treatment recommendations. The total time spent counseling a patient
      (greater than 30 minutes) and the number of years in practice (fewer than 10)
      predicted prostate cancer risk tool use (OR 2.4, p <0.01 and 3.4, p <0.01,
      respectively). CONCLUSIONS: AUA respondents use risk estimation tools more
      frequently in the pretreatment setting than in the prebiopsy setting. The time
      spent counseling patients and the time since graduation from residency predicted
      the likelihood of using risk estimation tools.

PMID- 25562445
TI  - Assessing health related benefit after reconstruction for urinary and fecal
      incontinence in children: a parental perspective.
AB  - PURPOSE: We sought to evaluate health related benefit in children undergoing
      surgical reconstruction for urinary and fecal incontinence from a parental
      perspective. MATERIALS AND METHODS: A health related benefit instrument was
      mailed to the parents or guardians of 300 consecutive patients who had undergone
      reconstruction for urinary and/or fecal incontinence at our institution between
      1997 and 2011. We assessed parent reported health related benefit using the
      validated Glasgow Children's Benefit Inventory and satisfaction with 6
      supplemental questions. One-sample t-tests as well as exploratory univariate and
      multivariate linear regressions were performed for statistical analysis. RESULTS:
      Response rate was 40.0% at a mean of 5.5 years (range 0.6 to 13.8) after
      reconstruction. Spina bifida was the most common primary diagnosis (48 patients,
      56.5%). Mean total Glasgow Children's Benefit Inventory score and subscores for
      each domain were positive, indicating an improved health related benefit after
      reconstruction (all p <0.0001). Certain patients, possibly based on diagnosis and
      gender, may particularly benefit from reconstruction (p <=0.04). Parents believed
      that the bladder augmentation and/or urinary continent catheterizable channel
      most changed the life of their child but that achievement of stool continence was
      most important to themselves. Only 17 families (16.2%) required more than 1 month
      to become comfortable with catheterizations, and 69 patients (68.8%) required
      less care or no assistance with daily activities after reconstruction. Only 2
      parents (1.9%) would be unwilling to consent to the procedure again. CONCLUSIONS:
      We observed moderate parental satisfaction and parent reported improvement in
      health related quality of life for children undergoing surgical reconstruction
      for urinary and fecal incontinence.

PMID- 25562446
TI  - Long-term renal functional outcomes after primary gastrocystoplasty.
AB  - PURPOSE: We assessed long-term renal function, morbidities and mortality in 50
      patients who had undergone primary gastrocystoplasty at our institution.
      MATERIALS AND METHODS: We retrospectively reviewed patients 21 years or younger
      who had undergone primary gastrocystoplasty between 1984 and 2004. Patients who
      underwent secondary gastrocystoplasty or primary composite augmentation or had
      cloacal exstrophy were excluded. Primary outcome was progression to end-stage
      renal disease. Secondary outcomes included mortality, bladder malignancy,
      hematuria-dysuria syndrome, electrolyte abnormalities and surgical revisions.
      RESULTS: Of 50 patients who had undergone gastrocystoplasty 35 met inclusion
      criteria. Median age was 9.4 years and 60% of the patients were male. Median
      followup was 19 years (IQR 11 to 25). Of the 35 patients 15 (43%) had normal
      preoperative estimated glomerular filtration rate and 5 (14%) had stage 2, 10
      (29%) stage 3 and 5 (14%) stage 4 chronic kidney disease. Five of the 15 patients
      with stage 3 or 4 chronic kidney disease improved to normal estimated glomerular
      filtration rate, 1 remained with stage 3 disease and 9 progressed to end-stage
      renal disease. In 1 patient with normal estimated glomerular filtration rate end
      stage renal disease developed following an episode of septic shock due to
      osteomyelitis. Seven patients in the cohort (20%) died, with 1 each dying of
      ventriculoperitoneal shunt infection, pneumonia, end-stage renal disease,
      complications of pregnancy and unknown cause, and 2 patients dying of septic
      shock due to urinary tract infection. There were no bladder malignancies.
      Hematuria-dysuria syndrome developed in 9 patients (24%). Eight patients (23%)
      underwent surgical revision. CONCLUSIONS: The majority of patients had preserved
      or improved renal function after gastrocystoplasty. There were no deaths
      attributable to gastric augmentation and no bladder malignancies. Approximately a
      fourth of patients required surgical revision.

PMID- 25562447
TI  - Code status discussions in psychiatric and medical inpatients.
AB  - BACKGROUND: The Patient Self-Determination Act along with regulatory standards
      and institutional standards of care highlight the need for collaboration between
      care providers and patients with respect to goals of care and, in emergency
      situations, code status and measures to be taken in keeping with patients'
      wishes. Addressing code status may be lacking in patients who require psychiatric
      hospitalization due to the nature of psychiatric illness, relative medical
      stability, and a general expectation of survival. We sought to compare code
      status documentation and discussion between psychiatric and medical inpatients,
      as this knowledge will help shape future interventions for process improvement.
      METHOD: We conducted a retrospective chart review of hospitalized patients in
      psychiatric and medical units during a 12-month period in 2008. For those with
      multiple admissions, we reviewed only the index (or first) hospitalization. Data
      collected included demographic information, clinical information regarding cancer
      as a primary diagnosis or a diagnosis that met National Hospice and Palliative
      Care Organization (NHPCO) guidelines, code status order and discussion
      documentation, the presence of an advance directive, length of stay, and 1-year
      mortality. Data were summarized using mean values, percentages, and frequencies.
      The 2 groups (psychiatric and medical groups) were compared. RESULTS: The charts
      of 276 psychiatric patients and 317 general medical patients were reviewed. More
      psychiatric patients had dementia (P < .001). Medical inpatients had a higher
      rate of code status order documented on admission (96% vs 65%, P < .001) and
      "full-code, discussed" order (67% vs 33%, P < .001). Psychiatric inpatients had
      more "do not resuscitate/do not intubate" orders (20% vs 13%, P = .037), more
      frequent changes in code status order (18% vs 7%, P < .001), and a higher
      percentage of advance directives (46% vs 25%, P < .001). CONCLUSIONS: A code
      status discussion with hospitalized patients needs to occur at admission
      regardless of reason for admission. Strategies are needed to improve this process
      for psychiatric inpatients.

PMID- 25562448
TI  - Lower response to early T-cell-dependent vaccination after neurotrauma or
      neurosurgery in adults.
AB  - BACKGROUND: Recent international guidelines recommend vaccination with a 13
      valent pneumococcal conjugate vaccine to reduce the risk of meningitis after
      neurotrauma with cerebrospinal fluid leak. The antibody response and optimal time
      point for vaccination have not been established and because the risk of
      meningitis is at the highest shortly after trauma, early vaccination is
      preferable. This study aimed to investigate the antibody response and to ensure
      that central nervous system injury-induced immunodepression did not affect the
      response to a T-cell-dependent conjugate vaccine when administered shortly after
      the injury. METHODS: So as not to interfere with routine pneumococcal
      vaccination, a conjugate vaccine against Haemophilus influenza type b (Hib) was
      chosen for the study. Thirty-three patients with basilar skull fracture and 23
      patients undergoing transsphenoidal pituitary gland surgery were vaccinated
      within 10 days after trauma/surgery and 29 control patients at least three weeks
      after trauma/surgery. Sera were collected pre- and post-vaccination for analysis
      of anti-Hib concentration. RESULTS: Four patients with post-vaccination target
      antibody concentration before vaccination were excluded from analysis. In the
      neurotrauma and neurosurgery groups 10/32 (31%) and 5/20 (25%) patients,
      respectively, were non-responders compared with 3/29 (10%) in the control group.
      Log10 anti-Hib concentrations in the neurotrauma, neurosurgery and control groups
      were 1.52 +/- 0.15, 1.38 +/- 0.15 and 1.81 +/- 0.12 MUg/ml, respectively.
      CONCLUSIONS: The majority of the patients responded to vaccination. However, the
      number of responders was significantly decreased and antibody concentration
      significantly lower in patients vaccinated early after the trauma/surgery.
      Investigation of the pneumococcal conjugate vaccine response in neurotrauma
      patients is therefore urgent.

PMID- 25562449
TI  - Discriminating between latent and active tuberculosis: the role of interleukin-2
      as biomarker.

PMID- 25562450
TI  - The Potyviridae P1a leader protease contributes to host range specificity.
AB  - The P1a protein of the ipomovirus Cucumber vein yellowing virus is one of the
      self-cleavage serine proteases present in Potyviridae family members. P1a is
      located at the N-terminal end of the viral polyprotein, and is closely related to
      potyviral P1 protease. For its proteolytic activity, P1a requires a still unknown
      host factor; this might be linked to involvement in host specificity. Here we
      built a series of constructs and chimeric viruses to help elucidate the role of
      P1a cleavage in host range definition. We demonstrate that host-dependent
      separation of P1a from the remainder of the polyprotein is essential for
      suppressing RNA silencing defenses and for efficient viral infection. These
      findings support the role of viral proteases as important determinants in host
      adaptation. 

PMID- 25562452
TI  - Deposition and depletion of maduramicin residues in eggs after oral
      administration to laying hens determined by LC-MS.
AB  - The coccidiostat maduramicin has been approved as a feed additive for chickens
      and turkeys, although it is prohibited for use in laying hens. In the present
      study, laying hens were divided into three groups and fed for 14 days with
      medicated feed containing maduramicin, at three different concentrations: 50, 100
      and 500 ug kg(-1). Eggs were collected during treatment and for 26 days after the
      end of feeding with medicated feed. Maduramicin residues were found exclusively
      in egg yolk, with the highest concentration in egg yolk of 459 ug kg(-1) for the
      highest dose. The maximum concentration of maduramicin in whole egg was 16.6 ug
      kg(-1) for the group receiving feed containing the maximum permitted level of
      maduramicin in feed (50 ug kg(-1)). The half-life of elimination of maduramicin,
      calculated for post-treatment days 1-10, was 6.5 days. Twelve days after drug
      administration, the concentration of the maduramicin in egg yolk for Group 3 (fed
      with 500 ug kg(-1) maduramicin) still exceeded 20 ug kg(-1), while the
      concentrations for Groups 1 and 2 were 1.2 and 2.7 ug kg(-1), respectively.

PMID- 25562451
TI  - Antidepressant actions of ketamine: from molecular mechanisms to clinical
      practice.
AB  - In the past decade the emergence of glutamate N-methyl-d-aspartate (NMDA)
      receptor blockers such as ketamine as fast-acting antidepressants fostered a
      major conceptual advance by demonstrating the possibility of a rapid
      antidepressant response. This discovery brings unique mechanistic insight into
      antidepressant action, as there is a substantial amount of basic knowledge on
      glutamatergic neurotransmission and how blockade of NMDA receptors may elicit
      plasticity. The combination of this basic knowledge base and the growing clinical
      findings will facilitate the development of novel fast acting antidepressants. 

PMID- 25562453
TI  - Lower extremity muscle activation in patients with or without chronic ankle
      instability during walking.
AB  - CONTEXT: Ankle sprains are among the most common musculoskeletal injuries, and
      many individuals with ankle sprains develop chronic ankle instability (CAI).
      Individuals with CAI exhibit proprioceptive and postural-control deficits, as
      well as altered osteokinematics, during gait. Neuromuscular activity is theorized
      to play a pivotal role in CAI, but deficits during walking are unclear.
      OBJECTIVE: To compare motor-recruitment patterns as demonstrated by surface
      electromyography amplitudes between participants with CAI and healthy control
      participants during walking. DESIGN: Descriptive laboratory study. SETTING:
      Laboratory. PATIENTS OR OTHER PARTICIPANTS: Fifteen adults with CAI (5 men, 10
      women; age = 23 +/- 4.2 years, height = 173 +/- 10.8 cm, mass = 72.4 +/- 14 kg)
      and 15 matched healthy control adults (5 men, 10 women; age = 22.9 +/- 3.4 years,
      height = 173 +/- 9.4 cm, mass = 70.8 +/- 18 kg). INTERVENTION(S): Participants
      walked shod on a treadmill while surface electromyography signals were recorded
      from the anterior tibialis, peroneus longus, lateral gastrocnemius, rectus
      femoris, biceps femoris, and gluteus medius muscles. MAIN OUTCOME MEASURE(S):
      Preinitial contact amplitude, postinitial contact amplitude, time of activation
      relative to initial contact, and percentage of activation time across the stride
      cycle were calculated for each muscle. RESULTS: Time of activation for all
      muscles tested occurred earlier in the CAI group than in the control group. The
      peroneus longus was activated for a longer duration across the entire stride
      cycle in the CAI group (36.0% +/- 10.3%) than the control group (23.3% +/- 22.2%;
      P = .05). No differences were noted between groups for measures of
      electromyographic amplitude at either preinitial or postinitial contact (P >
      .05). CONCLUSIONS: We identified differences between the CAI and control groups
      in the timing of muscle activation relative to heel strike in multiple lower
      extremity muscles and in the percentage of activation time across the entire
      stride cycle in the peroneus longus muscle. Individuals with CAI demonstrated
      neuromuscular-activation strategies throughout the lower extremity that were
      different from those of healthy control participants. Targeted therapeutic
      interventions for CAI may need to be focused on restoring normal neuromuscular
      function during gait.

PMID- 25562454
TI  - Plasma and electrolyte changes in exercising humans after ingestion of multiple
      boluses of pickle juice.
AB  - CONTEXT: Twenty-five percent of athletic trainers administer pickle juice (PJ) to
      treat cramping. Anecdotally, some clinicians provide multiple boluses of PJ
      during exercise but warn that repeated ingestion of PJ may cause hyperkalemia. To
      our knowledge, no researchers have examined the effect of ingesting multiple
      boluses of PJ on the same day or the effect of ingestion during exercise.
      OBJECTIVE: To determine the short-term effects of ingesting a single bolus or
      multiple boluses of PJ on plasma variables and to characterize changes in plasma
      variables when individuals ingest PJ and resume exercise. DESIGN: Crossover
      study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Nine euhydrated men
      (age = 23 +/- 4 years, height = 180.9 +/- 5.8 cm, mass = 80.7 +/- 13.8 kg, urine
      specific gravity = 1.009 +/- 0.005). INTERVENTION(S): On 3 days, participants
      rested for 30 minutes, and then a blood sample was collected. Participants
      ingested 0 or 1 bolus (1 mL . kg(-1) body weight) of PJ, donned sweat suits,
      biked vigorously for 30 minutes (approximate temperature = 37  degrees C,
      relative humidity = 18%), and had a blood sample collected. They either rested
      for 60 seconds (0- and 1-bolus conditions) or ingested a second 1 mL . kg(-1)
      body weight bolus of PJ (2-bolus condition). They resumed exercise for another 35
      minutes. A third blood sample was collected, and they exited the environmental
      chamber and rested for 60 minutes (approximate temperature = 21  degrees C,
      relative humidity = 18%). Blood samples were collected at 30 and 60 minutes
      postexercise. MAIN OUTCOME MEASURE(S): Plasma sodium concentration, plasma
      potassium concentration, plasma osmolality, and changes in plasma volume.
      RESULTS: The number of PJ boluses ingested did not affect plasma sodium
      concentration, plasma potassium concentration, plasma osmolality, or changes in
      plasma volume over time. The plasma sodium concentration, plasma potassium
      concentration, and plasma osmolality did not exceed 144.6 mEq . L(-1) (144.6 mmol
      . L(-1)), 4.98 mEq . L(-1) (4.98 mmol . L(-1)), and 289.5 mOsm . kg(-1)H2O,
      respectively, in any condition at any time. CONCLUSIONS: Ingesting up to 2
      boluses of PJ and resuming exercise caused negligible changes in blood variables.
      Ingesting up to 2 boluses of PJ did not increase plasma sodium concentration or
      cause hyperkalemia.

PMID- 25562455
TI  - A longitudinal pilot study of depressive symptoms in concussed and
      injured/nonconcussed National Collegiate Athletic Association Division I student
      athletes.
AB  - CONTEXT: Depression, which affects millions of Americans each year, among them
      collegiate student-athletes, can be caused by a wide range of circumstances,
      including sport-related injuries. OBJECTIVE: To longitudinally examine the extent
      to which National Collegiate Athletic Association Division I student-athletes
      demonstrated postinjury depressive symptoms. DESIGN: Descriptive epidemiologic
      study. SETTING: National Collegiate Athletic Association Division I collegiate
      athletics. PATIENTS OR OTHER PARTICIPANTS: Concussed, injured/nonconcussed, and
      healthy Division I collegiate student-athletes (aged 18-22 years) competing in
      men's basketball, football, and wrestling and women's basketball, soccer, and
      volleyball. MAIN OUTCOME MEASURE(S): Participants completed the Center for
      Epidemiologic Studies Depression Scale at baseline and at 1 week, 1 month, and 3
      months postinjury. We measured differences in depressive scores among concussed,
      injured/nonconcussed, and healthy participants. Longitudinal changes in
      postconcussion depressive symptoms were also examined. RESULTS: No differences in
      baseline depressive symptoms among subgroups were noted. After an increase
      between baseline and 1 week (4.3, 95% confidence interval [CI] = 0.41, 8.16, P =
      .02), depressive symptoms in the concussion group decreased between 1 week and 1
      month (-2.7, 95% CI = -4.96, -0.47, P = .01) and between 1 week and 3 months (
      4.0, 95% CI = -6.50, -1.49, P = .004). The injured/nonconcussed group showed
      differences between baseline and 1 week (4.6, 95% CI = 1.08, 8.17, P = .009) and
      between baseline and 1 month (3.2, 95% CI = -0.05, 6.30, P = .03). No significant
      differences were present in depressive symptoms between concussed participants
      and injured/nonconcussed participants at any of the postinjury time points.
      CONCLUSIONS: Depression may present as a postinjury sequela in Division I
      collegiate athletes. Athletes who sustain a concussion or other injury resulting
      in time lost from practice or competition need to be observed carefully for signs
      and symptoms that may indicate depression. Tools such as the Center for
      Epidemiologic Studies Depression Scale can be valuable in helping clinicians to
      recognize and manage depressive symptoms in these individuals.

PMID- 25562456
TI  - Athletic trainers' familiarity with and perceptions of academic accommodations in
      secondary school athletes after sport-related concussion.
AB  - CONTEXT: Sport-related concussion can affect athletes' sport participation and
      academic success. With the recent emphasis on cognitive rest, student-athletes
      may benefit from academic accommodations (AA) in the classroom; however, athletic
      trainers' (ATs') perceived familiarity with, and use of, AA is unknown.
      OBJECTIVE: To assess secondary school ATs' perceived familiarity with, attitudes
      and beliefs about, and incorporation of AA for student-athletes after sport
      related concussion. A secondary purpose was to determine whether employment
      status altered familiarity and use of AA. DESIGN: Cross-sectional study. SETTING:
      Online survey. PATIENTS OR OTHER PARTICIPANTS: Of 3286 possible respondents, 851
      secondary school ATs accessed the survey (response rate = 25.9%; 308 men [36.2%],
      376 women [44.2%], 167 respondents [19.6%] with sex information missing; age =
      37.3 +/- 10.1 years). MAIN OUTCOME MEASURE(S): Participants were solicited via e
      mail to complete the Beliefs, Attitudes and Knowledge Following Pediatric Athlete
      Concussion among Athletic Trainers employed in the secondary school setting
      (BAKPAC-AT) survey. The BAKPAC-AT assessed ATs' perceived familiarity,
      perceptions, and roles regarding 504 plans, Individualized Education Programs
      (IEPs), and returning student-athletes to the classroom. Independent variables
      were employment status (full time versus part time), employment model (direct
      versus outreach), years certified, and years of experience in the secondary
      school setting. The dependent variables were participants' responses to the AA
      questions. Spearman rank-correlation coefficients were used to assess
      relationships and Mann-Whitney U and chi(2) tests (P < .05) were used to identify
      differences. RESULTS: Respondents reported that approximately 41% of the student
      athletes whose sport-related concussions they managed received AA. Respondents
      employed directly by the school were more familiar with 504 plans (P < .001) and
      IEPs (P < .001) and had a greater belief that ATs should have a role in AA. Both
      the number of years certified and the years of experience at the secondary school
      were significantly correlated with perceived familiarity regarding 504 plans and
      IEPs. CONCLUSIONS: The ATs employed directly by secondary schools and those with
      more experience as secondary school ATs were more familiar with AA. Understanding
      AA is important for all ATs because cognitive rest and "return to learn" are
      becoming more widely recommended in concussion management.

PMID- 25562457
TI  - Balance training and center-of-pressure location in participants with chronic
      ankle instability.
AB  - CONTEXT: Chronic ankle instability (CAI) occurs in some people after a lateral
      ankle sprain and often results in residual feelings of instability and episodes
      of the ankle's giving way. Compared with healthy people, patients with CAI
      demonstrated poor postural control and used a more anteriorly and laterally
      positioned center of pressure (COP) during a single-limb static-balance task on a
      force plate. Balance training is an effective means of altering traditional COP
      measures; however, whether the overall location of the COP distribution under the
      foot also changes is unknown. OBJECTIVE: To determine if the spatial locations of
      COP data points in participants with CAI change after a 4-week balance-training
      program. DESIGN: Randomized controlled trial. SETTING: Laboratory. PATIENTS OR
      OTHER PARTICIPANTS: Thirty-one persons with self-reported CAI. INTERVENTION(S):
      Participants were randomly assigned to a 4-week balance-training program or no
      balance training. MAIN OUTCOME MEASURE(S): We collected a total of 500 COP data
      points while participants balanced using a single limb on a force plate during a
      10-second trial. The location of each COP data point relative to the geometric
      center of the foot was determined, and the frequency count in 4 sections
      (anteromedial, anterolateral, posteromedial, posterolateral) was analyzed for
      differences between groups. RESULTS: Overall, COP position in the balance
      training group shifted from being more anterior to less anterior in both eyes
      open trials (before trial = 319.1 +/- 165.4, after trial = 160.5 +/- 149.5; P =
      .006) and eyes-closed trials (before trial = 387.9 +/- 123.8, after trial = 189.4
      +/- 102.9; P < .001). The COP for the group that did not perform balance training
      remained the same in the eyes-open trials (before trial = 214.1 +/- 193.3, after
      trial = 230.0 +/- 176.3; P = .54) and eyes-closed trials (before trial = 326.9 +/
      134.3, after trial = 338.2 +/- 126.1; P = .69). CONCLUSIONS: In participants
      with CAI, the balance-training program shifted the COP location from
      anterolateral to posterolateral. The program may have repaired some of the
      damaged sensorimotor system pathways, resulting in a more optimally functioning
      and less constrained system.

PMID- 25562458
TI  - Reliability of goniometric and trigonometric techniques for measuring hip
      extension range of motion using the modified Thomas test.
AB  - CONTEXT: Goniometric assessment of hip-extension range of motion is a standard
      practice in clinical rehabilitation settings. A weakness of goniometric measures
      is that small errors in landmarking may result in substantial measurement error.
      A less commonly used protocol for measuring hip range of motion involves applying
      trigonometric principles to the length and vertical displacement of the upper
      part of the lower extremity to determine hip angle; however, the reliability of
      this measure has never been assessed using the modified Thomas test. OBJECTIVE:
      To compare the intrarater and interrater reliability of goniometric (GON) and
      trigonometric (TRIG) techniques for assessing hip-extension range of motion
      during the modified Thomas test. DESIGN: Controlled laboratory study. SETTING:
      Institutional athletic therapy facility. PATIENTS OR OTHER PARTICIPANTS: A total
      of 22 individuals (12 men, 10 women; age range, 18-36 years) with no pathologic
      knee or back conditions. MAIN OUTCOME MEASURE(S): Hip-extension range of motion
      of each participant during a modified Thomas test was assessed by 2 examiners
      with both GON and TRIG techniques in a randomly selected order on 2 separate
      days. RESULTS: The intraclass correlation coefficient (ICC) revealed that the
      reliability of the GON technique was low for both the intrarater (ICC = 0.51,
      0.54) and interrater (ICC = 0.30, 0.65) comparisons, but the reliability of the
      TRIG technique was high for both intrarater (ICC = 0.90, 0.95) and interrater
      (ICC = 0.91, 0.94) comparisons. Single-factorial repeated-measures analyses of
      variance revealed no mean differences in scoring within or between examiners for
      either measurement protocol, whereas a difference was observed when comparing the
      TRIG and GON tests due to the differences in procedures used to identify
      landmarks. CONCLUSIONS: Using the TRIG technique to measure hip-extension range
      of motion during the modified Thomas test results in superior intrarater and
      interrater reliability when compared with the GON technique.

PMID- 25562460
TI  - Oxidative umpolung alpha-alkylation of ketones.
AB  - We disclose a hypervalent iodine mediated alpha-alkylative umpolung reaction of
      carbonyl compounds with dialkylzinc as the alkyl source. The reaction is
      applicable to all common classes of ketones including 1,3-dicarbonyl compounds
      and regular ketones via their lithium enolates. The alpha-alkylated carbonyl
      products are formed in up to 93% yield. An ionic mechanism is inferred based on
      meticulous analysis, NMR studies, trapping and crossover experiments, and
      computational studies. 

PMID- 25562461
TI  - Expression and function of transcription factor AP-2? in early embryonic
      development of porcine parthenotes.
AB  - Transcription factor AP-2? (TFAP2C) is a member of the transcription factor
      activating enhancer binding protein (AP) family. In the present study we
      determined the temporal and spatial expression patterns of TFAP2C in porcine
      parthenotes during preimplantation development. Porcine TFAP2C transcripts were
      expressed at all stages of preimplantation development, with highest expression
      at the 8-cell stage. In contrast with the mouse, TFAP2C protein was not
      restricted to the trophectoderm and was also detected in the ICM in blastocyst
      stage porcine parthenotes. In knockdown (KD) experiments, most TFAP2C-depleted
      embryos were arrested before the compacted 8-cell stage. This developmental
      failure is attributed to abnormal expression of genes involved in cell adhesion,
      tight junction biogenesis and cell proliferation. Interestingly, although the
      conserved region 4 (CR4) of the porcine OCT4 5? upstream regionlacked the AP2C
      binding motif, OCT4 transcript levels were elevated in porcine TFAP2C-KD 8-cell
      embryos, suggesting TFAP2C may be involved in the regulation of OCT4 in porcine
      embryos through other mechanisms. In summary, the results suggest that TFAP2C is
      necessary for the transition from de novo transcript synthesis by activation to
      compaction and further development, and the different expression patterns of
      TFAP2C in porcine embryos may reflect species-specific functions during
      preimplantation embryo development.

PMID- 25562459
TI  - Tibiofemoral Osteoarthritis After Surgical or Nonsurgical Treatment of Anterior
      Cruciate Ligament Rupture: A Systematic Review.
AB  - OBJECTIVE:   To determine if surgical or nonsurgical treatment of anterior
      cruciate ligament rupture affects the prevalence of posttraumatic tibiofemoral
      osteoarthritis (OA). DATA SOURCES:   Studies published between 1983 and April
      2012 were identified via EBSCOhost and OVID. Reference lists were then screened
      in accordance with the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) statement. STUDY SELECTION:   Studies were included if (a)
      treatment outcomes focused on a direct comparison of surgical versus nonsurgical
      treatment of anterior cruciate ligament rupture, (b) the prevalence of
      tibiofemoral OA was reported, and (c) they were written in English. Studies were
      excluded if (a) the included patients were treated with cast immobilization after
      surgery, (b) the mean follow-up was less than 10 years, or (c) the patients
      underwent anterior cruciate ligament revision surgery. DATA EXTRACTION:   Two
      independent investigators reviewed the included articles using the Newcastle
      Ottawa Scale. Frequency of OA, surgical procedure, nonsurgical treatments, and
      participant characteristics were extracted and summarized. We calculated
      prevalence (%) and 95% confidence intervals for treatment groups for each
      individual study and overall. We developed 2 * 2 contingency tables to assess the
      association between treatment groups (exposed had surgery, referent was
      nonsurgical treatment) and the prevalence of OA. DATA SYNTHESIS:   Four
      retrospective studies were identified (140 surgical patients, 240 nonsurgical
      patients). The mean Newcastle-Ottawa Scale score was 5 (range = 4-6 [of 10]
      points). Average length of follow-up was 11.8 years (range = 10-14 years). The
      prevalence of OA for surgically treated patients ranged from 32.6% to 51.2%
      (overall = 41.4%, 95% confidence interval = 35.0%, 48.1%) and for nonsurgical
      patients ranged from 24.5% to 42.3% (overall = 30.9%, 95% confidence interval =
      24.4%, 38.3%). CONCLUSIONS:   Although OA prevalence was higher in the surgical
      treatment group at a mean follow-up of 11.8 years, no definitive evidence
      supports surgical or nonsurgical treatment after anterior cruciate ligament
      injury to prevent posttraumatic OA. Current studies have been limited by small
      sample sizes, low methodologic quality, and a lack of data regarding confounding
      factors.

PMID- 25562463
TI  - Sequence analysis and gene expression of potential components of copper transport
      and homeostasis in Thalassiosira pseudonana.
AB  - Genes involved with many Fe functions and some Cu functions are annotated in the
      Thalassiosira pseudonana Hasle et Heimdal genome. Using bioinformatics, we
      performed a systematic Blastp search to obtain all relevant sequences and to
      select the most complete gene models for putative components of Cu acquisition
      and distribution. We identified homologs of high-affinity Cu transporters (CTR),
      Cu transporting P1B-type ATPases, Cu chaperones and ZIP transporters. The
      putative CTRs in T. pseudonana have the conserved CTR Cu-binding motifs and
      transmembrane domains, and their gene expression was down-regulated by a Cu
      addition to low Cu acclimated cultures. The sequences of some putative TpZIPs
      were similar to those of well-known Zn and Fe transporters. Cu addition affected
      the expression of some TpZIP genes, suggesting an interaction between Cu
      metabolism and that of Zn and/or Fe. For intracellular Cu distribution, we
      identified putative Cu transporting P1B-type ATPases, proposed to deliver Cu to
      the trans-Golgi or the secretory compartment, as well as putative Cu chaperones,
      proposed to deliver Cu to the mitochondrion. Their gene expression was down
      regulated by a Cu addition, indicating that these putative intracellular Cu
      transporters and chaperones might redistribute Cu, allowing T. pseudonana to meet
      key metabolic needs under Cu deficiency. 

PMID- 25562465
TI  - Effects of number and position of meta and para carboxyphenyl groups of zinc
      porphyrins in dye-sensitized solar cells: structure-performance relationship.
AB  - Porphyrin sensitizers containing meta- and para-carboxyphenyl groups in their
      meso positions have been synthesized and investigated for their performance in
      dye-sensitized solar cells (DSSCs). The superior performance of para-derivative
      compared to meta-derivative porphyrins was revealed by optical spectroscopy,
      electrochemical property measurements, density functional theory (DFT)
      calculations, attenuated total reflectance-Fourier transform infrared (ATR-FTIR)
      spectroscopy, incident photon-to-current conversion efficiency (IPCE),
      electrochemical impedance spectroscopy (EIS), and stability performance.
      Absorption spectra of para-carboxyphenyl-substituted porphyrins on TiO2 show a
      broader Soret band compared to meta-carboxyphenyl-substituted porphyrins. ATR
      FTIR spectra of the studied porphyrins on TiO2 were applied to investigate the
      number and mode of carboxyl groups attached to TiO2. The VOC, JSC, and IPCE
      values of para-series porphyrins were distinctly superior to those of meta-series
      porphyrins. The Nyquist plots of the studied porphyrins show that charge
      injection in para-series porphyrins is superior to that in meta-series
      porphyrins. The orthogonally positioned para derivatives have more efficient
      charge injection and charge transfer over charge recombination, whereas the
      efficiencies of flat-oriented meta derivatives are retarded by rapid charge
      recombination. Photovoltaic measurements of the studied meta- and para
      carboxyphenyl-functionalized porphyrins show that the number and position of
      carboxyphenyl groups play a crucial role in the performance of the DSSC. Our
      results indicate that para-carboxyphenyl derivatives outperform meta
      carboxyphenyl derivatives to give better device performance. This study will
      serve as a guideline for the design and development of organic, porphyrin, and
      ruthenium dyes in DSSCs. 

PMID- 25562462
TI  - Initial response as a predictor of 12-week buprenorphine-naloxone treatment
      response in a prescription opioid-dependent population.
AB  - OBJECTIVE: Initial medication response has been shown to predict treatment
      outcome across a variety of substance use disorders, but no studies have examined
      the predictive power of initial response to buprenorphine-naloxone in the
      treatment of prescription opioid dependence. We therefore conducted a secondary
      analysis of data from the Prescription Opioid Addiction Treatment Study to
      determine whether initial response to buprenorphine-naloxone predicted 12-week
      treatment outcome in a prescription opioid-dependent population. METHOD: Using
      data from a multisite, randomized controlled trial of buprenorphine-naloxone plus
      counseling for DSM-IV prescription opioid dependence (June 2006-July 2009), we
      conducted a secondary analysis to investigate the relationship between initial
      medication response and 12-week treatment outcome to establish how soon the
      efficacy of buprenorphine-naloxone could be predicted (N = 360). Outcomes were
      determined from the Substance Use Report, a self-report measure of substance use,
      and confirmatory urinalysis. Predictive values were calculated to determine the
      importance of abstinence versus use at various time points within the first month
      of treatment (week 1, weeks 1-2, 1-3, or 1-4) in predicting successful versus
      unsuccessful treatment outcome (based on abstinence or near-abstinence from
      opioids) in the last 4 weeks of buprenorphine-naloxone treatment (weeks 9-12).
      RESULTS: Outcome was best predicted by medication response after 2 weeks of
      treatment. Two weeks of initial abstinence was moderately predictive of treatment
      success (positive predictive value = 71%), while opioid use in both of the first
      2 weeks was strongly predictive of unsuccessful treatment outcome (negative
      predictive value [NPV] = 84%), especially when successful outcome was defined as
      total abstinence from opioids in weeks 9-12 (NPV = 94%). CONCLUSIONS: Evaluating
      prescription opioid-dependent patients after 2 weeks of buprenorphine-naloxone
      treatment may help determine the likelihood of successful outcome at completion
      of the current treatment regimen. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT00316277.

PMID- 25562466
TI  - Acetic acid induces pH-independent cellular energy depletion in Salmonella
      enterica.
AB  - Weak organic acids are widely used as preservatives and disinfectants in the food
      industry. Despite their widespread use, the antimicrobial mode of action of
      organic acids is still not fully understood. This study investigated the effect
      of acetic acid on the cell membranes and cellular energy generation of four
      Salmonella strains. Using a nucleic acid/protein assay, it was established that
      acetic acid did not cause leakage of intracellular components from the strains. A
      scanning electron microscopy study further confirmed that membrane disruption was
      not the antimicrobial mode of action of acetic acid. Some elongated Salmonella
      cells observed in the micrographs indicated a possibility that acetic acid may
      inhibit DNA synthesis in the bacterial cells. Using an ATP assay, it was found
      that at a neutral pH, acetic acid caused cellular energy depletion with an
      ADP/ATP ratio in the range between 0.48 and 2.63 (p<0.05) that was apparent for
      the four Salmonella strains. We suggest that this effect was probably due solely
      to the action of undissociated acid molecules. The antimicrobial effect of acetic
      acid was better under acidic conditions (ADP/ATP ratio of 5.56 +/- 1.27; p<0.05),
      where the role of both pH and undissociated acid molecules can act together. We
      concluded that the inhibitory effect of acetic acid is not solely attributable to
      acidic pH but also to undissociated acid molecules. This finding has implication
      for the use of acetic acid as an antimicrobial against Salmonella on food
      products, such as chicken meat, which can buffer its pH.

PMID- 25562467
TI  - Grossly delayed massive subcutaneous emphysema following laparoscopic left
      hemicolectomy: A case report.
AB  - INTRODUCTION: Surgical emphysema is a known early complication of laparoscopic
      surgery, common during upper gastrointestinal and gynaecological surgery; the
      authors present the first case of delayed subcutaneous emphysema following a
      laparoscopic left hemicolectomy. PRESENTATION OF CASE: A 52-year-old woman
      underwent a laparoscopic left hemicolectomy for a sigmoid malignancy; on the
      third post-operative day after an uneventful procedure, she developed a massive
      surgical emphysema involving her face, neck and chest with associated
      pneumoperitoneum but without any evidence of pneumothorax. A gastrograffin enema
      ruled out an anastomotic leak. Apart from a borderline tachycardia, mildly low
      saturations and an area of erythema in her right flank, she was totally
      asymptomatic. The emphysema resolved spontaneously around the 6th post-operative
      day. DISCUSSION: Massive subcutaneous surgical emphysema after laparoscopic
      colorectal surgery is a rare complication and can me managed conservatively with
      a good outcome. CONCLUSION: To our knowledge, this represents the first case of
      delayed massive surgical emphysema following colorectal surgery, the aetiology of
      which has still not been clearly explained, after exclusion of the most common
      causes.

PMID- 25562468
TI  - Similarities and Differences in the Determinants of Trips Outdoors Performed by
      UK Urban- and Rural-Living Older Adults.
AB  - The frequency of trips outdoors is a strong indicator of older adults' physical
      activity levels. This qualitative study compared and contrasted determinants of
      trips outdoors between rural- (n = 13) and urban-living (n = 15) people aged 65
      and older living in England. Interview transcripts were analyzed through directed
      and summative content analysis employing the Ecological Model framework. Some
      personal-level determinants (age-related barriers) and environment-level factors
      (car dependence, bus services) were shared across samples. The main differences
      were seen in how a community-based social network instigated trips outdoors for
      rural participants while family ties mostly led to trips outdoors for urban
      living participants. Urban participants used and valued recreational facilities,
      but rural participants did not report them as important in determining trips
      outdoors. Strategies to improve public transport and minimize age-related
      barriers may translate from urban to rural contexts. However, social and/or
      physical environment interventions could be more effective if they were rural
      grounded, not urban-translated. 

PMID- 25562469
TI  - Effects of neuromuscular fatigue on perceptual-cognitive skills between genders
      in the contribution to the knee joint loading during side-stepping tasks.
AB  - This study investigated whether neuromuscular fatigue affects the neuromuscular
      control of an athlete within a sports context setting and whether these effects
      were more pronounced in the females. Lower limb joint kinetics of 6 male and 6
      female inter-varsity soccer players performing side-stepping tasks in non-fatigue
      versus fatigue and anticipated versus unanticipated conditions were quantified
      using 10 Motion Analysis Corporation cameras and a Kistler(TM) force platform.
      The Yo-Yo intermittent recovery Level 1 fatigue protocol was employed. Stance
      foot initial contact and peak forces, and peak joint knee moments of the lower
      limb were submitted to a 3-way mixed-model repeated measure ANOVA. The results
      suggested that males tend to elicit significantly higher knee joint loadings when
      fatigued. In addition, males elicited significantly higher peak proximal tibia
      anterior/posterior shear force, vertical ground reaction force at initial contact
      and peak internal rotational moments than females. These findings suggested that
      males were at greater overall injury risk than females, especially in the
      sagittal plane. Neuromuscular control-based training programmes/interventions
      that are designed to reduce the risk of the non-contact ACL injury need to be
      customised for the different genders. 

PMID- 25562470
TI  - Unlocking the functional properties in one-dimensional MoSI cluster polymers by
      doping and photoinduced charge transfer.
AB  - To improve functionalization of MoSI cluster polymers we have studied the effects
      of adsorption doping on the electrical transport, bundling, and optical
      absorption spectra. Doping results both in enhanced conductivity and aggregated
      bundles in dispersion. The different electronic properties of different bundle
      diameters can be ascribed to self-doping during the synthesis. Furthermore,
      doping shifts the characteristic absorption peaks and transfers oscillator
      strength to lower energies. Femtosecond optical spectroscopy shows that the
      spectral signature of adsorption and self-doping indeed originates from the
      population of electronic levels that are empty or absent in the undoped sample.
      The large spectral shifts and long lifetimes of photoinduced charges suggest
      efficient localization. 

PMID- 25562471
TI  - Tandem beta-elimination/hetero-michael addition rearrangement of an N-alkylated
      pyridinium oxime to an O-alkylated pyridine oxime ether: an experimental and
      computational study.
AB  - A novel OH(-)-promoted tandem reaction involving C(beta)-N(+)(pyridinium)
      cleavage and ether C(beta)-O(oxime) bond formation in aqueous media has been
      presented. The study fully elucidates the fascinating reaction behavior of N
      benzoylethylpyridinium-4-oxime chloride in aqueous media under mild reaction
      conditions. The reaction journey begins with the exclusive beta-elimination and
      formation of pyridine-4-oxime and phenyl vinyl ketone and ends with the formation
      of O-alkylated pyridine oxime ether. A combination of experimental and
      computational studies enabled the introduction of a new type of rearrangement
      process that involves a unique tandem reaction sequence. We showed that (E)-O
      benzoylethylpyridine-4-oxime is formed in aqueous solution by a base-induced
      tandem beta-elimination/hetero-Michael addition rearrangement of (E)-N
      benzoylethylpyridinium-4-oximate, the novel synthetic route to this engaging
      target class of compounds. The complete mechanistic picture of this rearrangement
      process was presented and discussed in terms of the E1cb reaction scheme within
      the rate-limiting beta-elimination step. 

PMID- 25562472
TI  - A bright new day.

PMID- 25562473
TI  - A defining era for the Academy.

PMID- 25562476
TI  - Vision screening for children 36 to <72 months: recommended practices.
AB  - PURPOSE: This article provides recommendations for screening children aged 36 to
      younger than 72 months for eye and visual system disorders. The recommendations
      were developed by the National Expert Panel to the National Center for Children's
      Vision and Eye Health, sponsored by Prevent Blindness, and funded by the Maternal
      and Child Health Bureau of the Health Resources and Services Administration,
      United States Department of Health and Human Services. The recommendations
      describe both best and acceptable practice standards. Targeted vision disorders
      for screening are primarily amblyopia, strabismus, significant refractive error,
      and associated risk factors. The recommended screening tests are intended for use
      by lay screeners, nurses, and other personnel who screen children in educational,
      community, public health, or primary health care settings. Characteristics of
      children who should be examined by an optometrist or ophthalmologist rather than
      undergo vision screening are also described. RESULTS: There are two current best
      practice vision screening methods for children aged 36 to younger than 72 months:
      (1) monocular visual acuity testing using single HOTV letters or LEA Symbols
      surrounded by crowding bars at a 5-ft (1.5 m) test distance, with the child
      responding by either matching or naming, or (2) instrument-based testing using
      the Retinomax autorefractor or the SureSight Vision Screener with the Vision in
      Preschoolers Study data software installed (version 2.24 or 2.25 set to minus
      cylinder form). Using the Plusoptix Photoscreener is acceptable practice, as is
      adding stereoacuity testing using the PASS (Preschool Assessment of Stereopsis
      with a Smile) stereotest as a supplemental procedure to visual acuity testing or
      autorefraction. CONCLUSIONS: The National Expert Panel recommends that children
      aged 36 to younger than 72 months be screened annually (best practice) or at
      least once (accepted minimum standard) using one of the best practice approaches.
      Technological updates will be maintained at
      http://nationalcenter.preventblindness.org.

PMID- 25562477
TI  - Vision and eye health in children 36 to <72 months: proposed data definitions.
AB  - PURPOSE: To recommend a standardized approach for measuring progress toward
      national goals to improve preschool children's eye health. METHODS: A
      multidisciplinary panel of experts reviewed existing measures and national vision
      related goals during a series of face-to-face meetings and conference calls. The
      panel used a consensus process, informed by existing data related to delivery of
      eye and non-eye services to preschool children. RESULTS: Currently, providers of
      vision screening and eye examinations lack a system to provide national- or state
      level estimates of the proportion of children who receive either a vision
      screening or an eye examination. The panel developed numerator and denominator
      definitions to measure rates of children "who completed a vision screening in a
      medical or community setting using a recommended method, or received an eye
      examination by an optometrist or ophthalmologist at least once between the ages
      of 36 to <72 months." A separate measure for children with neurodevelopmental
      disorders and measures for eye examination and follow-up were also developed. The
      panel recommended that these measures be implemented at national, state, and
      local levels. CONCLUSIONS: Standardized performance measures that include all eye
      services received by a child are needed at state and national levels to measure
      progress toward improving preschool children's eye health.

PMID- 25562478
TI  - Vision and eye health in children 36 to <72 months: proposed data system.
AB  - PURPOSE: This article provides a rationale for developing an integrated data
      system for recording vision screening and eye care follow-up outcomes in
      preschool-aged children. The recommendations were developed by the National
      Expert Panel to the National Center for Children's Vision and Eye Health at
      Prevent Blindness and funded by the Maternal and Child Health Bureau of the
      Health Resources and Services Administration, US Department of Health and Human
      Services. Guidance is provided regarding specific elements to be included, as
      well as the characteristics and architecture of such a data system. Vision
      screening for preschool-aged children is endorsed by many organizations concerned
      with children's health issues. Currently, there is a lack of data on the
      proportion of children screened and no effective system to ensure that children
      who fail screenings access appropriate comprehensive eye examinations and follow
      up care. RESULTS: The expansion of currently existing, or developing integrated
      health information systems, which would include child-level vision screening
      data, as well as referral records and follow-up diagnosis and treatment, is
      consistent with the proposed national approach to an integrated health
      information system (National Health Information Infrastructure). Development of
      an integrated vision data system will enhance eye health for young children at
      three different levels: (1) the child level, (2) the health care provider level,
      and (3) an epidemiological level. CONCLUSIONS: It is critical that the end users,
      the professionals who screen children and the professionals who provide eye care,
      be involved in the development and implementation of the proposed integrated data
      systems. As essential stakeholders invested in ensuring quality eye care for
      children, this community of professionals should find increasing need and
      opportunities at local, state, and national levels to contribute to cooperative
      guidance for data system development.

PMID- 25562479
TI  - Daily disposable contact lenses versus spectacles in teenagers.
AB  - PURPOSE: To compare clinical and subjective quality-of-life (QoL) data for
      teenagers wearing daily disposable contact lenses or spectacles. METHODS: This
      open-label study randomized subjects (aged 13 to 19 years) with no previous
      contact lens wear experience to nelfilcon A (DAILIES AquaComfort Plus) contact
      lenses or spectacles for 6 months. A full clinical workup, as well as subjective
      QoL measures using the Pediatric Refractive Error Profile and Quality of Life
      Impact of Refractive Correction questionnaires, was conducted at baseline and at
      week 4 and months 3 and 6, with an additional study visit at week 2 for subjects
      randomized to wear contact lenses. RESULTS: A total of 110 teenagers were
      enrolled in the study; 13 discontinued before study completion, 10 (17.5%) from
      the contact lens group and 3 (5.7%) from the spectacle group (p = 0.04). Visual
      acuity was good for both groups at all study visits. Biomicroscopy assessments
      were similar at baseline for both groups. Significant differences in Pediatric
      Refractive Error Profile responses were noted between vision correction groups
      across visits for appearance (p < 0.001), satisfaction (p < 0.001), activities (p
      < 0.001), peer perception (p = 0.003), and overall score (p < 0.001). For Quality
      of Life Impact of Refractive Correction, the contact lens group gave more
      favorable responses than the spectacle group (p = 0.02). After 6 months of
      wearing contact lenses, teenagers had a more positive attitude toward comfort,
      vision, and safety with contact lenses. No serious adverse events were reported
      during the study. CONCLUSIONS: The daily disposable lenses used in this study are
      suitable for vision correction for teenagers, offering improvements in QoL
      measures during the first month of wear, including appearance, satisfaction,
      activities, and peer perceptions, without negatively impacting vision or eye
      health. Teenagers were able to handle contact lenses with the same amount of
      confidence as spectacles.

PMID- 25562483
TI  - Direct links between the vernalization response and other key traits of cereal
      crops.
AB  - Transcription of the vernalization1 gene (VRN1) is induced by prolonged cold
      (vernalization) to trigger flowering of cereal crops, such as wheat and barley.
      VRN1 encodes a MADS box transcription factor that promotes flowering by
      regulating the expression of other genes. Here we use transcriptome sequencing
      (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) to identify
      direct targets of VRN1. Over 500 genomic regions were identified as potential
      VRN1-binding targets by ChIP-seq. VRN1 binds the promoter of flowering locus T
      like 1, a promoter of flowering in vernalized plants. VRN1 also targets
      vernalization2 and ODDSOC2, repressors of flowering that are downregulated in
      vernalized plants. RNA-seq identified additional VRN1 targets that might play
      roles in triggering flowering. Other targets of VRN1 include genes that play
      central roles in low-temperature-induced freezing tolerance, spike architecture
      and hormone metabolism. This provides evidence for direct regulatory links
      between the vernalization response pathway and other important traits in cereal
      crops.

PMID- 25562484
TI  - Patient-centered medical homes for patients with disabilities.
AB  - The patient-centered medical home is an innovative approach to improve health
      care outcomes. To address the unique needs of patients with intellectual and
      developmental disabilities (IDDs), a large health care provider reevaluated the
      National Committee for Quality Assurance's 6 medical home standards: (a) enhance
      access and continuity, (b) identify and manage patient populations, (c) plan and
      manage care, (d) provide self-care and community support, (e) track and
      coordinate care, and (f) measure and improve performance. This article describes
      issues to consider when serving patients with IDDs. 

PMID- 25562485
TI  - A highly efficient polysulfide mediator for lithium-sulfur batteries.
AB  - The lithium-sulfur battery is receiving intense interest because its theoretical
      energy density exceeds that of lithium-ion batteries at much lower cost, but
      practical applications are still hindered by capacity decay caused by the
      polysulfide shuttle. Here we report a strategy to entrap polysulfides in the
      cathode that relies on a chemical process, whereby a host--manganese dioxide
      nanosheets serve as the prototype--reacts with initially formed lithium
      polysulfides to form surface-bound intermediates. These function as a redox
      shuttle to catenate and bind 'higher' polysulfides, and convert them on reduction
      to insoluble lithium sulfide via disproportionation. The sulfur/manganese dioxide
      nanosheet composite with 75 wt% sulfur exhibits a reversible capacity of 1,300 mA
      h g(-1) at moderate rates and a fade rate over 2,000 cycles of 0.036%/cycle,
      among the best reported to date. We furthermore show that this mechanism extends
      to graphene oxide and suggest it can be employed more widely.

PMID- 25562487
TI  - Enantioselective carbolithiation of S-alkenyl-N-aryl thiocarbamates: kinetic and
      thermodynamic control.
AB  - The addition of n-butyllithium to alkenylthiocarbamates in the presence of (-)
      sparteine or the (+)-sparteine surrogate leads to asymmetric carbolithiation, and
      returns enantiomerically enriched thiocarbamate derivatives of secondary thiols.
      In THF, with the (+)-sparteine surrogate, in situ aryl migration leads to an
      enantiomerically enriched tertiary thiol derivative. Remarkably, the two
      pseudoenantiomeric chiral ligands do not always give enantiomeric products,
      probably as a result of a complex interplay of kinetic and thermodynamic control.
      In situ IR and NMR studies of a stable, hindered lithiated thiocarbamate
      demonstrated its chemical and configurational stability over a period of hours at
      0  degrees C. 

PMID- 25562488
TI  - Unravelling the physics of size-dependent dislocation-mediated plasticity.
AB  - Size-affected dislocation-mediated plasticity is important in a wide range of
      materials and technologies. Here we develop a generalized size-dependent
      dislocation-based model that predicts strength as a function of crystal/grain
      size and the dislocation density. Three-dimensional (3D) discrete dislocation
      dynamics (DDD) simulations reveal the existence of a well-defined relationship
      between strength and dislocation microstructure at all length scales for both
      single crystals and polycrystalline materials. The results predict a transition
      from dislocation-source strengthening to forest-dominated strengthening at a size
      dependent critical dislocation density. It is also shown that the Hall-Petch
      relationship can be physically interpreted by coupling with an appropriate
      kinetic equation of the evolution of the dislocation density in polycrystals. The
      model is shown to be in remarkable agreement with experiments. This work presents
      a micro-mechanistic framework to predict and interpret strength size-scale
      effects, and provides an avenue towards performing multiscale simulations without
      ad hoc assumptions. 

PMID- 25562489
TI  - Hierarchical layered double hydroxide nanocomposites: structure, synthesis and
      applications.
AB  - Layered double hydroxide (LDH)-based nanocomposites, constructed by interacting
      LDH nanoparticles with other nanomaterials (e.g. silica nanoparticles and
      magnetic nanoparticles) or polymeric molecules (e.g. proteins), are an emerging
      yet active area in healthcare, environmental remediation, energy conversion and
      storage. Combining advantages of each component in the structure and functions,
      hierarchical LDH-based nanocomposites have shown great potential in biomedicine,
      water purification, and energy storage and conversion. This feature article
      summarises the recent advances in LDH-based nanocomposites, focusing on their
      synthesis, structure, and application in drug delivery, bio-imaging, water
      purification, supercapacitors, and catalysis. 

PMID- 25562490
TI  - Design of a highly potent HIV-1 fusion inhibitor targeting the gp41 pocket.
AB  - OBJECTIVE: T20 (Enfuvirtide), which is a 36-residue peptide derived from the C
      terminal heptad repeat (CHR) of gp41, is the only clinically available HIV-1
      fusion inhibitor, but it easily induces drug resistance, which calls for next
      generation drugs. DESIGN: We recently demonstrated that the M-T hook structure
      can be used to design a short CHR peptide that specifically targets the conserved
      gp41 pocket rather than the T20-resistant sites. We attempted to develop more
      potent HIV-1 fusion inhibitors based on the structure-activity relationship of MT
      SC22EK. METHODS: Multiple biophysical and functional approaches were performed to
      determine the structural features, binding affinities and anti-HIV activities of
      the inhibitors. RESULTS: The 23-residue peptide HP23, which mainly contains the M
      T hook structure and pocket-binding sequence, showed a helical and trimeric state
      in solution. HP23 had dramatically improved binding stability and antiviral
      activity, and it was the most potent inhibitor of the M-T hook-modified and
      unmodified control peptides. More promisingly, HP23 was highly active in the
      inhibition of diverse HIV-1 subtypes, including T20 and MT-SC22EK resistant HIV-1
      mutants, and it exhibited a high genetic barrier to the development of
      resistance. CONCLUSION: Our studies delivered an ideal HIV-1 fusion inhibitor
      that specifically targeted the highly conserved gp41 pocket and possessed potent
      binding and antiviral activity. Furthermore, HP23 can serve as a critical tool to
      explore the mechanisms of HIV-1 fusion and inhibition.

PMID- 25562486
TI  - Electrochemiluminescence assays for insulin and glutamic acid decarboxylase
      autoantibodies improve prediction of type 1 diabetes risk.
AB  - We recently developed new electrochemiluminescence (ECL) insulin autoantibody
      (IAA) and glutamic acid decarboxylase 65 autoantibody (GADA) assays that
      discriminate high-affinity, high-risk diabetes-specific autoantibodies from low
      affinity, low-risk islet autoantibodies (iAbs) detected by radioassay (RAD).
      Here, we report a further validation of the ECL-IAA and -GADA assays in 3,484
      TrialNet study participants. The ECL assay and RAD were congruent in those with
      prediabetes and in subjects with multiple autoantibodies, but only 24% (P<0.0001)
      of single RAD-IAA-positive and 46% (P<0.0001) of single RAD-GADA-positive were
      confirmed by the ECL-IAA and -GADA assays, respectively. During a follow-up
      (mean, 2.4 years), 51% of RAD-IAA-positive and 63% of RAD-GADA-positive subjects
      not confirmed by ECL became iAb negative, compared with only 17% of RAD-IAA
      positive (P<0.0001) and 15% of RAD-GADA-positive (P<0.0001) subjects confirmed by
      ECL assays. Among subjects with multiple iAbs, diabetes-free survival was
      significantly shorter if IAA or GADA was positive by ECL and negative by RAD than
      if IAA or GADA was negative by ECL and positive by RAD (P<0.019 and P<0.0001,
      respectively). Both positive and negative predictive values in terms of
      progression to type 1 diabetes mellitus were superior for ECL-IAA and ECL-GADA,
      compared with RADs. The prevalence of the high-risk human leukocyte antigen
      DR3/4, DQB1*0302 genotype was significantly higher in subjects with RAD-IAA or
      RAD-GADA confirmed by ECL. In conclusion, both ECL-IAA and -GADA are more disease
      specific and better able to predict the risk of progression to type 1 diabetes
      mellitus than the current standard RADs. 

PMID- 25562491
TI  - Mx2 expression is associated with reduced susceptibility to HIV infection in
      highly exposed HIV seronegative Kenyan sex workers.
AB  - INTRODUCTION: Recent studies have identified Mx2 as a novel HIV-1 innate
      restriction factor that inhibits proviral integration. A pilot proteomic study of
      immune cells from highly exposed HIV-seronegative (HESN) individuals enrolled in
      the Pumwani sex worker cohort identified Mx1 as potential correlate of HIV
      protection. A detailed population level analysis of Mx1 and Mx2 expression and
      their role in reduced susceptibility to HIV infection in HESN women was
      conducted. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from
      102 HESN women and 100 high-risk negative controls enrolled in a Nairobi-based
      sex worker cohort. Whole-cell lysates were prepared and analyzed for Mx1 and Mx2
      expression by commercial ELISA. Bivariate and multiple linear regression analyses
      were conducted to account for confounding epidemiological factors. RESULTS: Mx2,
      but not Mx1, was found to be significantly overexpressed in HESN women compared
      with high-risk negative controls (P = 0.027). After multiple linear regression
      analysis, accounting for age, menopause, pregnancy, Depo-Provera use, recent
      infections and medication usage, Mx2 expression remained significantly
      overexpressed in the PBMC of HESN women (P = 0.05). Additionally, an interaction
      model analysis indicated that HESN women who use Depo-Provera have 2.6-fold
      higher levels of Mx2 than any other group (P < 0.001). No associations with Mx1
      expression were observed. CONCLUSION: This is the first epidemiological report of
      Mx2 and its association with altered susceptibility to HIV infection in HESN
      women. Additionally, we show that HESN women who use Depo-Provera have the
      highest levels of Mx2 expression, highlighting a possible mechanism for hormonal
      modulation of HIV susceptibility.

PMID- 25562492
TI  - Trends in and correlates of CD4+ cell count at antiretroviral therapy initiation
      after changes in national ART guidelines in Rwanda.
AB  - BACKGROUND: Initiation of antiretroviral therapy (ART) in the advanced stages of
      HIV infection remains a major challenge in sub-Saharan Africa. This study was
      conducted to better understand barriers and enablers to timely ART initiation in
      Rwanda where ART coverage is high and national ART eligibility guidelines first
      expanded in 2007-2008. METHODS: Using data on 6326 patients (>=15 years) at five
      Rwandan clinics, we assessed trends and correlates of CD4 cell count at ART
      initiation and the proportion initiating ART with advanced HIV disease (CD4 <200
      cells/MUl or WHO stage IV). RESULTS: Out of 6326 patients, 4486 enrolling in HIV
      care initiated ART with median CD4 cell count of 211 cells/MUl [interquartile
      range: 131-300]. Median CD4 cell counts at ART initiation increased from 183
      cells/MUl in 2007 to 293 cells/MUl in 2011-2012, and the proportion with advanced
      HIV disease decreased from 66.2 to 29.4%. Factors associated with a higher odds
      of advanced HIV disease at ART initiation were male sex [adjusted odds ratios
      (AOR) = 1.7; 95% confidence interval (CI): 1.3-2.1] and older age (AOR46
      55+vs.<25 = 2.3; 95% CI: 1.2-4.3). Among those initiating ART more than 1 year
      after enrollment in care, those who had a gap in care of 12 or more months prior
      to ART initiation had higher odds of advanced HIV disease (AOR = 5.2; 95% CI: 1.2
      21.1). CONCLUSION: Marked improvements in the median CD4 cell count at ART
      initiation and proportion initiating ART with advanced HIV disease were observed
      following the expansion of ART eligibility criteria in Rwanda. However, sex
      disparities in late treatment initiation persisted through 2011-2012, and
      appeared to be driven by later diagnosis and/or delayed linkage to care among
      men.

PMID- 25562494
TI  - Age-specific and sex-specific weight gain norms to monitor antiretroviral therapy
      in children in low-income and middle-income countries.
AB  - BACKGROUND: Viral load and CD4% are often not available in resource-limited
      settings for monitoring children's responses to antiretroviral therapy (ART). We
      aimed to construct normative curves for weight gain at 6, 12, 18, and 24 months
      following initiation of ART in children, and to assess the association between
      poor weight gain and subsequent responses to ART. DESIGN: Analysis of data from
      HIV-infected children younger than 10 years old from African and Asian clinics
      participating in the International epidemiologic Databases to Evaluate AIDS.
      METHODS: The generalized additive model for location, scale, and shape was used
      to construct normative percentile curves for weight gain at 6, 12, 18, and 24
      months following ART initiation. Cox proportional models were used to assess the
      association between lower percentiles (< 50th) of weight gain distribution at the
      different time points and subsequent death, virological suppression, and
      virological failure. RESULTS: Among 7173 children from five regions of the world,
      45% were underweight at baseline. Weight gain below the 50th percentile at 6, 12,
      18, and 24 months of ART was associated with increased risk of death, independent
      of baseline characteristics. Poor weight gain was not associated with increased
      hazards of virological suppression or virological failure. CONCLUSION: Monitoring
      weight gain on ART using age-specific and sex-specific normative curves
      specifically developed for HIV-infected children on ART is a simple, rapid,
      sustainable tool that can aid in the identification of children who are at
      increased risk of death in the first year of ART.

PMID- 25562493
TI  - Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected
      children born to HIV-infected mothers.
AB  - OBJECTIVES: We evaluated the potential cardiac effects of in-utero exposures to
      antiretroviral drugs in HIV-exposed but uninfected (HEU) children. DESIGN AND
      METHODS: We compared echocardiographic parameters of left ventricular function
      (ejection fraction, fractional shortening, and stress-velocity index) and
      structure (left ventricular dimension, posterior wall/septal thickness, mass,
      thickness-to-dimension ratio, and wall stress) (expressed as Z-scores to account
      for age and body surface area) between HEU and HIV-unexposed cohorts from the
      Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities
      study. Within the HEU group, we investigated the associations between the
      echocardiographic Z-scores and in-utero exposures to maternal antiretroviral
      drugs. RESULTS: There were no significant differences in echocardiographic Z
      scores between 417 HEU and 98 HIV-unexposed children aged 2-7 years. Restricting
      the analysis to HEU children, first-trimester exposures to combination
      antiretroviral therapy (a regimen including at least three antiretroviral drugs)
      and to certain specific antiretroviral drugs were associated with significantly
      lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to
      combination antiretroviral therapy was also associated with lower left
      ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester
      exposure to combination antiretroviral therapy was associated with higher mean
      left ventricular posterior wall thickness and lower mean left ventricular wall
      stress Z-scores. CONCLUSION: There was no evidence of significant cardiac
      toxicity of perinatal combination antiretroviral therapy exposure in HEU
      children. Subclinical differences in left ventricular structure and function with
      specific in-utero antiretroviral exposures indicate the need for a longitudinal
      cardiac study in HEU children to assess long-term cardiac risk and cardiac
      monitoring recommendations.

PMID- 25562495
TI  - Growth patterns in the first year of life differ in infants born to perinatally
      vs. nonperinatally HIV-infected women.
AB  - OBJECTIVE: To compare the growth patterns in the first year of life between
      children born to perinatally HIV-infected (PHIV) vs. nonperinatally HIV-infected
      (NPHIV) women in the United States. DESIGN: Retrospective cohort study of HIV
      infected pregnant women who received care and delivered a live-born at two urban
      tertiary centers from January 2004 to March 2012. METHODS: We collected data via
      chart review on demographics, behavioral risk factors, HIV clinical markers,
      combination antiretroviral therapy (cART), mode of HIV acquisition, pregnancy
      outcomes, and infant anthropometrics on study participants. Mixed-effects models
      were used to assess the association between maternal mode of HIV acquisition and
      weight-for-age z-score (WAZ), length-for-age z-score (LAZ), and weight-for-length
      z-score (WLZ). RESULTS: Of the 152 pregnancies evaluated, 32 and 120 infants were
      born to 25 PHIV and 99 NPHIV women, respectively. Infants of PHIV women exhibited
      lower mean WAZ and LAZ throughout the first year of life in unadjusted analyses.
      After adjusting for potential confounders, the relationship between PHIV women
      and LAZ persisted (beta = -0.54, P = 0.026). Small-for-gestational age for each
      birth anthropometric parameter (birth length, birth weight, and both birth length
      and weight) was associated with decreased LAZ (beta = -0.48, P = 0.007), WAZ
      (beta = -0.99, P < 0.001), and WLZ (beta = -0.36, P = 0.027), respectively. A
      delivery HIV RNA level below 400 copies/ml was associated with increased WAZ and
      WLZ (beta = 0.43, P = 0.015 and beta = 0.38, P = 0.021, respectively).
      CONCLUSIONS: Infants of PHIV women may remain at persistently decreased lengths
      throughout the first year of life. Further studies aimed at understanding
      intrauterine and environmental factors in PHIV women are warranted.

PMID- 25562497
TI  - Time for a systematic look at inactivated HIV vaccines.

PMID- 25562498
TI  - HIV inactivation: time for a second look.

PMID- 25562496
TI  - Dramatic decline in substance use by HIV-infected pregnant women in the United
      States from 1990 to 2012.
AB  - OBJECTIVE: We aimed to describe temporal changes in substance use among HIV
      infected pregnant women in the United States from 1990 to 2012. DESIGN: Data came
      from two prospective cohort studies (Women and Infants Transmission Study and
      Surveillance Monitoring for Antiretroviral Therapy Toxicities Study). METHODS:
      Women were classified as using a substance during pregnancy if they self-reported
      use or had a positive biological sample. To account for correlation between
      repeated pregnancies by the same woman, generalized estimating equation models
      were used to test for temporal trends and evaluate predictors of substance use.
      RESULTS: Over the 23-year period, substance use among the 5451 HIV-infected
      pregnant women sharply declined; 82% of women reported substance use during
      pregnancy in 1990, compared with 23% in 2012. Use of each substance decreased
      significantly (P < 0.001 for each substance) in an approximately linear fashion,
      until reaching a plateau in 2006. Multivariable models showed substance use was
      inversely associated with receiving antiretroviral therapy. Among the subset of
      824 women with multiple pregnancies under observation, women who used a substance
      in their previous pregnancy were at elevated risk of substance use during their
      next pregnancy (risk ratio, 5.71; 95% confidence interval, 4.63-7.05).
      CONCLUSION: A substantial decrease in substance use during pregnancy was observed
      between 1990 and 2012 in two large US cohorts of HIV-infected women. Substance
      use prevalence in these cohorts became similar to that of pregnant women in the
      general US population by the mid-2000s, suggesting that the observed decrease may
      be due to an epidemiological transition of the HIV epidemic among women in the
      United States.

PMID- 25562499
TI  - Different expression of Blimp-1 in HIV infection may be used to monitor disease
      progression and provide a clue to reduce immune activation and viral reservoirs.

PMID- 25562500
TI  - The elephant and the blind men: making sense of the seemingly multifaceted role
      of Blimp-1 in HIV-1 infection.

PMID- 25562501
TI  - Data-driven approach to optimum wavelength selection for diffuse optical imaging.
AB  - The production of accurate and independent images of the changes in concentration
      of oxyhemoglobin and deoxyhemoglobin by diffuse optical imaging is heavily
      dependent on which wavelengths of near-infrared light are chosen to interrogate
      the target tissue. Although wavelengths can be selected by theoretical methods,
      in practice the accuracy of reconstructed images will be affected by wavelength
      specific and system-specific factors such as laser source power and detector
      sensitivity. We describe the application of a data-driven approach to optimum
      wavelength selection for the second generation of University College London's
      multichannel, time-domain optical tomography system (MONSTIR II). By performing a
      functional activation experiment using 12 different wavelengths between 690 and
      870 nm, we were able to identify the combinations of 2, 3, and 4 wavelengths
      which most accurately reproduced the results obtained using all 12 wavelengths
      via an imaging approach. Our results show that the set of 2, 3, and 4 wavelengths
      which produce the most accurate images of functional activation are [770, 810],
      [770, 790, 850], and [730, 770, 810, 850] respectively, but also that the system
      is relatively robust to wavelength selection within certain limits. Although
      these results are specific to MONSTIR II, the approach we developed can be
      applied to other multispectral near-infrared spectroscopy and optical imaging
      systems.

PMID- 25562502
TI  - Activation detection in functional near-infrared spectroscopy by wavelet
      coherence.
AB  - Functional near-infrared spectroscopy (fNIRS) detects hemodynamic responses in
      the cerebral cortex by transcranial spectroscopy. However, measurements recorded
      by fNIRS not only consist of the desired hemodynamic response but also consist of
      a number of physiological noises. Because of these noises, accurately detecting
      the regions that have an activated hemodynamic response while performing a task
      is a challenge when analyzing functional activity by fNIRS. In order to better
      detect the activation, we designed a multiscale analysis based on wavelet
      coherence. In this method, the experimental paradigm was expressed as a binary
      signal obtained while either performing or not performing a task. We convolved
      the signal with the canonical hemodynamic response function to predict a possible
      response. The wavelet coherence was used to investigate the relationship between
      the response and the data obtained by fNIRS at each channel. Subsequently, the
      coherence within a region of interest in the time-frequency domain was summed to
      evaluate the activation level at each channel. Experiments on both simulated and
      experimental data demonstrated that the method was effective for detecting
      activated channels hidden in fNIRS data.

PMID- 25562504
TI  - Total synthesis of brazilin.
AB  - Described herein is a highly efficient total synthesis of brazilin from
      commercially available starting materials in 9 steps with 70% overall yield.
      Mitsunobu coupling followed by In(III)-catalyzed alkyne-aldehyde metathesis
      allowed for rapid construction of brazilin core skeleton in quantitative yield.
      Subsequent modulation of oxidation levels and acid-catalyzed cyclization led to
      the trimethyl ether of brazilin. Asymmetric dihydroxylation of the key
      intermediate was also demonstrated, which would permit asymmetric access to (+)
      brazilin. 

PMID- 25562503
TI  - Caseoperoxidase, mixed beta-casein-SDS-hemin-imidazole complex: a nano artificial
      enzyme.
AB  - A novel peroxidase-like artificial enzyme, named "caseoperoxidase", was
      biomimetically designed using a nano artificial amino acid apo-protein
      hydrophobic pocket. This four-component nano artificial enzyme containing heme
      imidazole-beta-casein-SDS exhibited high activity growth and k(cat) performance
      toward the native horseradish peroxidase demonstrated by the steady state
      kinetics using UV-vis spectrophotometry. The hydrophobicity and secondary
      structure of the caseoperoxidase were studied by ANS fluorescence and circular
      dichroism spectroscopy. Camel beta-casein (Cbeta-casein) was selected as an
      appropriate apo-protein for the heme active site because of its innate
      flexibility and exalted hydrophobicity. This selection was confirmed by homology
      modeling method. Heme docking into the newly obtained Cbeta-casein structure
      indicated one heme was mainly incorporated with Cbeta-casein. The presence of a
      main electrostatic site for the active site in the Cbeta-casein was also
      confirmed by experimental methods through Wyman binding potential and isothermal
      titration calorimetry. The existence of Cbeta-casein protein in this biocatalyst
      lowered the suicide inactivation and provided a suitable protective role for the
      heme active-site. Additional experiments confirmed the retention of
      caseoperoxidase structure and function as an artificial enzyme.

PMID- 25562505
TI  - Disintegration kinetics of food gels during gastric digestion and its role on
      gastric emptying: an in vitro analysis.
AB  - The understanding of the disintegration and gastric emptying of foods in the
      stomach is important for designing functional foods. In this study, a dynamic
      stomach model (human gastric simulator, HGS) was employed to investigate the
      disintegration and subsequent emptying of two differently structured whey protein
      emulsion gels (soft and hard gels).The gels were mechanically ground into
      fragments to reproduce the particle size distribution of an in vivo gel bolus.
      The simulated gel bolus was prepared by mixing gel fragments and artificial
      saliva, and exposed to 5 hours of simulated gastric digestion in the presence and
      absence of pepsin. Results showed that regardless of pepsin, the soft gel always
      disintegrated faster than the hard gel. The presence of pepsin significantly
      accelerated the disintegration of both gels. In particular, it enhanced abrasion
      of the soft gel into fine particles (<0.425 mm) after 180 min of processing. The
      emptying of the gels was influenced by the combined effects of the original
      particle size of the gel boluses and their disintegration kinetics in the HGS. In
      the presence or absence of pepsin, the larger particles of the soft gel emptied
      slower than the hard one during the first 120 min of process. However, in the
      presence of pepsin, the soft gel emptied faster than the hard one after 120 min
      because of a higher level of disintegration. These findings highlight the role of
      food structure, bolus properties and biochemical effects on the disintegration
      and gastric emptying patterns of gels during gastric digestion. 

PMID- 25562506
TI  - Transfer hydrogenation of unsaturated bonds in the absence of base additives
      catalyzed by a cobalt-based heterogeneous catalyst.
AB  - A novel non-noble Co@C-N catalytic system has been developed for catalytic
      transfer hydrogenation reactions. Co@C-N was found to be highly active and
      selective in the hydrogenation of a variety of unsaturated bonds with isopropanol
      in the absence of base additives. 

PMID- 25562507
TI  - Insights into the effects of 2:1 "sandwich-type" crown-ether/metal-ion complexes
      in responsive host-guest systems.
AB  - In-depth investigations of the specific ion-responsive characteristics based on
      2:1 "sandwich" structures and effects of crown ether cavity sizes on the metal
      ion/crown-ether complexation are systematically performed with a series of PNIPAM
      based responsive copolymers containing similar contents of crown ether units with
      different cavity dimensions (12-crown-4 (12C4), 15-crown-5 (15C5), 18-crown-6
      (18C6)). The lower critical solution temperature (LCST) values of copolymers in
      deionized water shift to lower temperatures gradually when the crown ether
      contents increase or the ring sizes decrease from 18C6 to 12C4. With increasing
      the concentrations of alkali metal ions (Na(+), K(+), Cs(+)) or the contents of
      pendent crown ether groups, the copolymers with different crown ether cavity
      sizes exhibit higher selectivity and sensitivity to corresponding cations.
      Importantly, the ion sensitivities of the copolymers in response to corresponding
      alkali metal ions increase dramatically with an increase in the crown ether
      cavity size. Interestingly, a linear relationship between the crown ether cavity
      size and the diameter of corresponding cation for the formation of stable 2:1
      "sandwich" complexes is found for the first time, from which the size of metal
      ions or other guests that able to form 2:1 "sandwich" complexes with crown ethers
      can be deduced. The results in this work are valuable and useful for further
      developments and practical applications of various crown-ether-based smart
      materials. 

PMID- 25562508
TI  - Recombinant BMP4 and BMP7 increase activin A production by up-regulating inhibin
      betaA subunit and furin expression in human granulosa-lutein cells.
AB  - CONTEXT: Granulosa cell-derived activins play important roles in the regulation
      of ovarian functions. To date, there is limited information pertaining to the
      intracellular regulation, assembly, and secretion of endogenous activin A in
      human granulosa cells. OBJECTIVE: The aim of this study was to examine the
      effects of BMP4 and BMP7 on furin expression and activin A production as well as
      the underlying mechanisms of action in human granulosa cells. DESIGN: An
      established immortalized human granulosa cell line (SVOG) and primary granulosa
      lutein cells were used as study models. Expression of inhibin subunits and furin
      as well as activin A accumulation were examined after exposure to recombinant
      human BMP4 or BMP7. A BMP type I receptor inhibitor (dorsomorphin), a furin
      inhibitor (Decanoyl-Arg-Val-Lys-Arg-chloromethylketone), and small interfering
      RNAs targeting SMAD4 and furin were used to verify the specificity of the effects
      and investigate potential mechanisms. SETTING: The study was conducted in an
      academic center. MAIN OUTCOME MEASURES: Specific mRNA and protein levels were
      examined using real time qPCR and Western blot. Activin A levels were measured
      using enzyme immunoassay. RESULTS: Treatment with bone morphogenetic protein
      (BMP) 4 and BMP7 significantly increased furin mRNA and protein, inhibin betaA
      mRNA, and activin A accumulation. Pre-treatment with dorsomorphin or SMAD4
      knockdown reversed the stimulatory effects of BMP4 and BMP7 on furin and inhibin
      betaA expression. In addition, furin knockdown or pre-treatment with a furin
      inhibitor attenuated the BMP4- and BMP7-induced accumulation of activin A.
      CONCLUSION: Recombinant BMP4 and BMP7 increase the production of bioactive mature
      activin A by up-regulating both the production and proteolytic processing of
      inhibin betaA subunit in human granulosa cells. The enhancement of inhibin betaA
      subunit processing is attributable to a SMAD-dependent up-regulation of its
      proprotein convertase, furin. These findings provide a potential mechanism by
      which theca cells can regulate neighboring granulosa cells in the ovary.

PMID- 25562509
TI  - Hormone modeling in preterm neonates: establishment of pituitary and steroid
      hormone reference intervals.
AB  - CONTEXT: Reports suggest significant differences in serum levels of hormones in
      extremely preterm compared with late preterm and full-term infants. OBJECTIVES:
      The purpose of this study was to develop reference intervals (RIs) for 3
      pituitary hormones and 5 steroid hormones in serum of preterm infants. DESIGN:
      Blood samples were collected from 248 (128 male and 120 female) preterm neonates
      born between 24 and 32 weeks' gestation. SETTING: PARTICIPANTS were recruited
      from 3 neonatal intensive care wards in Melbourne, Australia. PARTICIPANTS: No
      infant in this cohort had ambiguous genitalia or other endocrine abnormalities.
      All infants included in the RI determination survived beyond the equivalent of
      term. INTERVENTIONS: Serum was analyzed for prolactin, FSH, and LH by automated
      electrochemiluminescence immunoassay (Roche Cobas 8000-e601). Liquid
      chromatography coupled with tandem mass spectrometry was used for analysis of 17
      hydroxyprogesterone, androstenedione, cortisol, cortisone, and testosterone. MAIN
      OUTCOME MEASURES: The robust method was applied to define the central 95% RI,
      after each hormone measure was transformed using a Box-Cox transformation to
      correct for asymmetry. RESULTS: RIs were established for 8 hormones. Gender
      specific intervals were developed for FSH, LH, and testosterone. Cortisone and 17
      hydroxyprogesterone required division based on gestational age, with neonates
      born at <30 weeks' gestation demonstrating higher levels than their older
      counterparts. Androstenedione, cortisol, and prolactin did not require any
      division within this cohort for RI assignment. CONCLUSIONS: This report provides
      the first characterization of serum steroids measured by mass spectrometry in
      preterm neonates, with the additional characterization of 3 pituitary hormones in
      infants born at <=32 weeks' gestation. Use of these data allows for correct
      interpretation of results for very preterm neonates and reduces the risk of
      incorrect diagnosis due to misinterpretation of data.

PMID- 25562510
TI  - Randomized controlled trial of the effect of additional functional exercise
      during slow-stream rehabilitation in a regional center.
AB  - OBJECTIVE: To evaluate whether adding functional exercise training to standard
      physiotherapy during residential slow-stream rehabilitation (SSR) improves
      discharge outcomes and functional ability. DESIGN: Randomized controlled trial.
      SETTING: A regional hospital. PARTICIPANTS: Older people (N=60) admitted to SSR.
      INTERVENTION: All participants received standard physiotherapy. An individualized
      functional incidental training (FIT) program was implemented for intervention
      participants consisting of 4 extra episodes of functional exercise daily for the
      period of SSR. Research assistants visited twice weekly to practice and progress
      FIT programs. MAIN OUTCOME MEASURES: Outcome measures included discharge
      destination, participant-expected discharge destination, and functional tests of
      the Berg Balance Scale (BBS), de Morton Mobility Index (DEMMI), and 5 times sit
      to-stand test (FTSTS) at admission and discharge. RESULTS: Fifty-two participants
      completed the study. At baseline, the SSR group achieved higher scores on the
      BBS, DEMMI, and FTSTS. There was no significant difference in discharge
      destination between groups (P=.305). The difference in functional change between
      groups from admission to discharge on the BBS, DEMMI, and FTSTS was not
      significant. Participant-expected discharge destination was significantly
      associated with eventual discharge destination (chi1(2)=8.40, P=.004).
      CONCLUSIONS: Adding FIT to standard physiotherapy did not improve discharge
      outcomes and did not have a statistically significant effect on function, but may
      have a small effect on balance. Patient expected and actual discharge
      destinations were associated.

PMID- 25562511
TI  - Dual oxidase 2 generated reactive oxygen species selectively mediate the
      induction of mucins by epidermal growth factor in enterocytes.
AB  - Dual oxidase 2 enzyme is a member of the reactive oxygen species-generating cell
      membrane NADPH oxidases involved in mucosal innate immunity. It is not known if
      the biological activity of dual oxidase 2 is mediated by direct bacterial killing
      by reactive oxygen species produced by the enzyme or by the same reactive oxygen
      species acting as second messengers that stimulate novel gene expression. To
      uncover the role of reactive oxygen species and dual oxidases as signaling
      molecules, we have dissected the pathway triggered by epidermal growth factor to
      induce mucins, the principal protective components of gastrointestinal mucus. We
      show that dual oxidase 2 is essential for selective epidermal growth factor
      induction of the transmembrane MUC3 and the secreted gel-forming MUC5AC mucins.
      Reactive oxygen species generated by dual oxidase 2 stabilize tyrosine
      phosphorylation of epidermal growth factor receptor and induce MUC3 and MUC5AC
      through persistent activation of extracellular signal-regulated kinases 1/2
      protein kinase C. Knocking down dual oxidase 2 by selective RNA targeting (siRNA)
      reduced epidermal growth factor receptor phosphorylation, and MUC3 and MUC5AC
      gene expression. Extracellular reactive oxygen species produced by dual oxidase
      2, upon stimulation by epidermal growth factor, stabilize epidermal growth factor
      receptor phosphorylation and activate extracellular signal-regulated kinases 1/2
      protein kinase C which induce MUC5AC and MUC3. Extracellular reactive oxygen
      species produced by dual oxidase 2 that are known to directly kill bacteria, also
      contribute to the maintenance of the epidermal growth factor-amplification loop,
      which induces mucins. These data suggest a new function of dual oxidase 2 protein
      in the luminal protection of the gastrointestinal tract through the induction of
      mucin expression by growth factors. 

PMID- 25562512
TI  - Resveratrol mimics insulin activity in the adipogenic commitment of human bone
      marrow mesenchymal stromal cells.
AB  - Bone marrow mesenchymal stromal cells (BM-MSCs) are multipotent cells capable of
      differentiating toward osteoblatic and adipocytic phenotypes. BM-MSCs play
      several key roles including bone remodeling, establishment of hematopoietic niche
      and immune tolerance induction. Here, we investigated the effect of resveratrol
      (RSV), a therapeutically promising natural polyphenol, on the commitment of human
      BM-MSCs primary cultures. Cell differentiation was evaluated by means of
      morphological analysis, specific staining and expression of osteogenic and
      adipocytic master genes (Runx-2, PPARgamma). To maintain BM-MSC multipotency, all
      experiments were performed on cells at very early passages. At any concentration
      RSV, added to standard medium, did not affect the phenotype of confluent BM-MSCs,
      while, when added to osteogenic or adipogenic medium, 1 MUM RSV enhances the
      differentiation toward osteoblasts or adipocytes, respectively. Conversely, the
      addition of higher RSV concentration (25 MUM) to both differentiation media
      resulted exclusively in BM-MSCs adipogenesis. Surprisingly, the analysis of RSV
      molecular effects demonstrated that the compound completely substitutes insulin,
      a key component of adipogenic medium. We also observed that RSV treatment is
      associated to enhanced phosphorylation of CREB, a critical effector of insulin
      adipogenic activity. Finally, our observations contribute to the mechanistic
      elucidation of the well-known RSV positive effect on insulin sensitivity and type
      2 diabetes mellitus.

PMID- 25562513
TI  - Inhibition of thymidylate synthase by 2',2'-difluoro-2'-deoxycytidine
      (Gemcitabine) and its metabolite 2',2'-difluoro-2'-deoxyuridine.
AB  - 2',2'-Difluoro-2'-deoxycytidine (dFdC, gemcitabine) is a cytidine analogue active
      against several solid tumor types, such as ovarian, pancreatic and non-small cell
      lung cancer. The compound has a complex mechanism of action. Because of the
      structural similarity of one metabolite of dFdC, dFdUMP, with the natural
      substrate for thymidylate synthase (TS) dUMP, we investigated whether dFdC and
      its deamination product 2',2'-difluoro-2'-deoxyuridine (dFdU) would inhibit TS.
      This study was performed using two solid tumor cell lines: the human ovarian
      carcinoma cell line A2780 and its dFdC-resistant variant AG6000. The specific TS
      inhibitor Raltitrexed (RTX) was included as a positive control. Using the in situ
      TS activity assay measuring the intracellular conversion of [5-(3)H]-2'
      deoxyuridine or [5-(3)H]-2'-deoxycytidine to dTMP and tritiated water, it was
      observed that dFdC and dFdU inhibited TS. In A2780 cells after a 4h exposure to 1
      MUM dFdC tritium release was inhibited by 50% but did not increase after 24h,
      Inhibition was also observed following dFdU at 100 MUM. No effect was observed in
      the dFdC-resistant cell line AG6000; in this cell line only RTX had an inhibitory
      effect on TS activity. In the A2780 cell line RTX inhibited TS in a time
      dependent manner. In addition, DNA specific compounds such as 2'-C-cyano-2'-deoxy
      1-beta-D-arabino-pentafuranosylcytosine and aphidicoline were utilized to exclude
      DNA inhibition mediated down regulation of the thymidine kinase. Inhibition of
      the enzyme resulted in a relative increase of mis-incorporation of [5-(3)H]-2'
      deoxyuridine into DNA. In an attempt to elucidate the mechanism of in situ TS
      inhibition the ternary complex formation and possible inhibition in cellular
      extracts of A2780 cells, before and after exposure to dFdC, were determined. With
      the applied methods no proof for formation of a stable complex was found. In
      simultaneously performed experiments with 5FU such a complex formation could be
      demonstrated. However, using purified TS it was demonstrated that dFdUMP and not
      dFdCMP competitively inhibited TS with a Ki of 130 MUM, without ternary complex
      formation. In conclusion, in this paper we reveal a new target of dFdC:
      thymidylate synthase.

PMID- 25562514
TI  - A complex relative motion between hairpin loop 2 and transmembrane domain 5 in
      the glutamate transporter GLT-1.
AB  - Excitatory amino acid transporter 2, also known as glial glutamate transporter
      type 1 (GLT-1), plays an important role in maintaining suitable synaptic
      glutamate concentrations. Reentrant helical hairpin loop (HP) 2, as the
      extracellular gate, has been shown to participate in the binding of substrate and
      ions. Several residues in transmembrane domain (TM) 5 have been shown to be
      involved in the construction of the transport pathway. However, the spatial
      relationship between HP2 and TM5 during the recycling of glutamate has not yet
      been clarified. We introduced cysteine residue pairs in HP2 and TM5 of cysteine
      less-GLT-1 by using site-directed mutagenesis in order to assess the proximity of
      HP2 and TM5. A significant decrease in substrate uptake was seen in the
      I283C/S443C and S287C/S443C mutants when the oxidative cross-linking agent
      copper(II) (1,10-phenanthroline)3 (CuPh) was used. The inhibitory effect of CuPh
      on the transport activity of the S287/S443C mutant was increased after the
      application of glutamate or potassium. In contrast, an apparent protection of the
      transport activity of the I283C/S443C mutant was observed after glutamate or
      potassium addition. The membrane-impermeable sulfhydryl reagent (2
      trimethylammonium) methanethiosulfonate (MTSET) was used to detect the aqueous
      permeability of each single mutant. The aqueous permeability of the I283C mutant
      was identical to that of the S443C mutant. The sensitivity of I283C and S443C to
      MTSET was attenuated by glutamate and potassium. All these data indicate that
      there is a complex relative motion between TM5 and HP2 during the transport
      cycle. 

PMID- 25562515
TI  - Improved plasma membrane expression of the trafficking defective P344R mutant of
      muscle, skeletal, receptor tyrosine kinase (MuSK) causing congenital myasthenic
      syndrome.
AB  - Muscle, skeletal, receptor tyrosine kinase (MuSK) is a key organizer at the
      postsynaptic membrane and critical for proper development and maintenance of the
      neuromuscular junction. Mutations in MUSK result in congenital myasthenic
      syndrome (CMS). We hypothesized that the CMS-causing missense mutation (P344R),
      found within the cysteine-rich domain of the protein, will affect its
      conformational tertiary structure. Consequently, the protein will misfold, get
      retained in the endoplasmic reticulum (ER) and lose its biological function
      through degradation by the highly conserved ER associated degradation (ERAD)
      machinery. We report that P344R-MuSK mutant is trafficking-deficient when
      expressed at 37 degrees C in HeLa, COS-7 and HEK293 cell lines. It colocalized
      with the ER marker calnexin in contrast to wild-type MuSK which localized to the
      plasma membrane. The N-glycosylation status of P344R-MuSK is that of an immature
      and not properly post-translationally modified protein. Inhibition of protein
      synthesis showed that the P344R mutant's half-life is shorter than wild-type MuSK
      protein. Proteasomal inhibition resulted in the stabilization of the mutant
      protein. The mutant protein is highly ubiquitinated compared to wild-type
      confirming targeting for proteasomal degradation. The mutant showed around 50% of
      its in vivo autophosphorylation activity. P344R-MuSK mutant's trafficking defect
      is correctable by culturing the expressing cells at 27 degrees C. Moreover,
      chemical compounds namely 2.5% glycerol, 1% dimethyl sulfoxide, 10 MUM
      thapsigargin and 1 MUM curcumin improved the maturation and exit of the mutant
      protein from the ER. These findings open perspectives for potential therapeutic
      intervention for patients with CMS harboring the P344R-MuSK mutation.

PMID- 25562516
TI  - Trypanosoma brucei J protein 2 is a stress inducible and essential Hsp40.
AB  - Hsp40 proteins (also known as DnaJ or J proteins) serve as co-chaperones for
      Hsp70, but also display evidence of independent chaperone function. Furthermore,
      certain Hsp40s have been shown to be stress-inducible and essential.
      Trypanosomatids display a remarkable diversification of Hsp40 proteins, with
      numerous distinct Hsp40-like proteins encoded in the Trypanosoma brucei genome.
      This study investigated the role of one of the six T. brucei Type I Hsp40s, T.
      brucei J protein 2 (Tbj2). We found that Tbj2 was heat stress-inducible, and that
      knockdown using RNA interference resulted in a severe growth defect under normal
      growth temperatures. Furthermore, a green fluorescent protein (GFP)-Tbj2 fusion
      protein was found to be localized to the cytosol of T. brucei. Taken together,
      these data suggest that Tbj2 is not functionally equivalent to the other five
      Type I Hsp40s, and that it is an essential, cytosolic, and stress-inducible
      chaperone, potentially playing an important role in protein biogenesis in T.
      brucei. 

PMID- 25562517
TI  - Compartmentalized zinc deficiency and toxicities caused by ZnT and Zip gene over
      expression result in specific phenotypes in Drosophila.
AB  - Movement of zinc ions across cellular membranes is achieved mainly by two
      families of zinc transport genes encoding multi-transmembrane domain proteins.
      Members of the Zip family generally transport zinc into the cytosol, either from
      outside the cell or from the lumen of subcellular organelles such as the
      endoplasmic reticulum, Golgi, endosomes or storage vacuoles. ZnT proteins move
      zinc in the opposite direction, resulting in efflux from the cell or uptake into
      organelles. Zinc homeostasis at both the cellular and systemic level is achieved
      by the coordinated action of numerous Zip and ZnT proteins, twenty-four in
      mammals and seventeen in the vinegar fly Drosophila melanogaster. Previously, we
      have identified a zinc toxicity phenotype in the Drosophila eye, caused by
      targeted over expression of dZip42C.1 (dZip1) combined with knockdown of dZnT63C
      (dZnT1). In general, this phenotype was rescued by increased zinc efflux or
      decreased uptake and was exacerbated by decreased efflux or increased uptake. Now
      we have identified three additional zinc dyshomeostasis phenotypes caused by over
      expression of dZnT86D, dZnT86D(eGFP) and dZip71B(FLAG). Genetic and dietary
      manipulation experiments showed that these three phenotypes all differ both from
      each other and from our original zinc toxicity phenotype. Based on these data and
      the approximate subcellular localization of each zinc transport protein, we
      propose that each phenotype represents a different redistribution of zinc within
      these cells, resulting in a Golgi zinc toxicity, a Golgi zinc deficiency and a
      combined Golgi/other organelle zinc toxicity respectively. We are able to group
      the remaining Drosophila Zip and ZnT genes into several functional categories
      based on their interaction with the three novel zinc dyshomeostasis phenotypes,
      allowing the role of each zinc transport protein to be defined in greater detail.
      This research highlights the differential effects that redistribution of zinc can
      have within a particular tissue and identifies the Golgi as being particularly
      sensitive to both excess and insufficient zinc. 

PMID- 25562518
TI  - Programmable sensors of 5-hydroxymethylcytosine.
AB  - 5-Hydroxymethylcytosine (hmC), the sixth base of the mammalian genome, is
      increasingly recognized as an epigenetic mark with important biological
      functions. We report engineered, programmable transcription-activator-like
      effectors (TALEs) as the first DNA-binding receptor molecules that provide
      direct, individual selectivities for cytosine (C), 5-methylcytosine (mC), and hmC
      at user-defined DNA sequences. Given the wide applicability of TALEs for
      programmable targeting of DNA sequences in vitro and in vivo, this provides broad
      perspectives for epigenetic research. 

PMID- 25562519
TI  - Personalized cancer care conference.
AB  - The Oslo University Hospital (Norway), the K.G. Jebsen Centre for Breast Cancer
      Research (Norway), The Radiumhospital Foundation (Norway) and the Fritz-Bender
      Foundation (Germany) designed under the conference chairmen (E. Mihich, K.S.
      Zanker, A.L. Borresen-Dale) and advisory committee (A. Borg, Z. Szallasi, O.
      Kallioniemi, H.P. Huber) a program at the cutting edge of "PERSONALIZED CANCER
      CARE: Risk prediction, early diagnosis, progression and therapy resistance." The
      conference was held in Oslo from September 7 to 9, 2012 and the science-based
      presentations concerned six scientific areas: (1) Genetic profiling of patients,
      prediction of risk, late side effects; (2) Molecular profiling of tumors and
      metastases; (3) Tumor-host microenvironment interaction and metabolism; (4)
      Targeted therapy; (5) Translation and (6) Informed consent, ethical challenges
      and communication. Two satellite workshops on (i) Ion Ampliseq-a novel tool for
      large scale mutation detection; and (ii) Multiplex RNA ISH and tissue homogenate
      assays for cancer biomarker validation were additionally organized. The report
      concludes that individual risk prediction in carcinogenesis and/or
      metastatogenesis based on polygenic profiling may be useful for intervention
      strategies for health care and therapy planning in the future. To detect distinct
      and overlapping DNA sequence alterations in tumor samples and adjacent normal
      tissues, including point mutations, small insertions or deletions, copy number
      changes and chromosomal rearrangements will eventually make it possible to design
      personalized management plans for individualized patients. However, large
      individualized datasets need a new approach in bio-information technology to
      reduce this enormous data dimensionally to simply working hypotheses about health
      and disease for each individual. 

PMID- 25562520
TI  - Machine learning techniques for arterial pressure waveform analysis.
AB  - The Arterial Pressure Waveform (APW) can provide essential information about
      arterial wall integrity and arterial stiffness. Most of APW analysis frameworks
      individually process each hemodynamic parameter and do not evaluate inter
      dependencies in the overall pulse morphology. The key contribution of this work
      is the use of machine learning algorithms to deal with vectorized features
      extracted from APW. With this purpose, we follow a five-step evaluation
      methodology: (1) a custom-designed, non-invasive, electromechanical device was
      used in the data collection from 50 subjects; (2) the acquired position and
      amplitude of onset, Systolic Peak (SP), Point of Inflection (Pi) and Dicrotic
      Wave (DW) were used for the computation of some morphological attributes; (3) pre
      processing work on the datasets was performed in order to reduce the number of
      input features and increase the model accuracy by selecting the most relevant
      ones; (4) classification of the dataset was carried out using four different
      machine learning algorithms: Random Forest, BayesNet (probabilistic), J48
      (decision tree) and RIPPER (rule-based induction); and (5) we evaluate the
      trained models, using the majority-voting system, comparatively to the respective
      calculated Augmentation Index (AIx). Classification algorithms have been proved
      to be efficient, in particular Random Forest has shown good accuracy (96.95%) and
      high area under the curve (AUC) of a Receiver Operating Characteristic (ROC)
      curve (0.961). Finally, during validation tests, a correlation between high risk
      labels, retrieved from the multi-parametric approach, and positive AIx values was
      verified. This approach gives allowance for designing new hemodynamic morphology
      vectors and techniques for multiple APW analysis, thus improving the arterial
      pulse understanding, especially when compared to traditional single-parameter
      analysis, where the failure in one parameter measurement component, such as Pi,
      can jeopardize the whole evaluation. 

PMID- 25562521
TI  - Motivations and barriers to sharing biological samples: a case study.
AB  - One of the most significant impediments to the current goals of genomic research
      is the limited availability of high quality biological samples. Despite efforts
      to increase both the quality and quantity of samples collected, access to such
      samples remains limited. This may be due, at least in part, to a general
      reluctance of biobanking professionals, clinicians, and researchers to share
      biological specimens with others. Ethnographic methods were used in a biobank
      setting to explore professionals' perspectives toward and practices of sharing
      samples. Several motivations and barriers to sharing that may influence research
      practice were identified. Contrary to existing literature that suggests that
      professionals are unlikely to share samples with one another, the participants of
      this study were open to and supportive of sharing samples for research. However,
      clear communication and effective infrastructure are needed to support the
      distribution of biobank materials. 

PMID- 25562522
TI  - Physician Awareness and Utilization of Food and Drug Administration (FDA)
      Approved Labeling for Pharmacogenomic Testing Information.
AB  - We surveyed 10,303 United States physicians on where they obtain pharmacogenomic
      testing information. Thirty-nine percent indicated that they obtained this from
      drug labeling. Factors positively associated with this response included older
      age, postgraduate instruction, using other information sources, regulatory
      approval/ recommendation of testing, reliance on labeling for information, and
      perception that patients have benefited from testing. Physicians use
      pharmacogenomic testing information from drug labeling, highlighting the
      importance of labeling information that is conducive to practice application. 

PMID- 25562523
TI  - A nickel phosphine complex as a fast and efficient hydrogen production catalyst.
AB  - Here we report the electrocatalytic reduction of protons to hydrogen by a novel
      S2P2 coordinated nickel complex, [Ni(bdt)(dppf)] (bdt = 1,2-benzenedithiolate,
      dppf = 1,1'-bis(diphenylphosphino)ferrocene). The catalysis is fast and efficient
      with a turnover frequency of 1240 s(-1) and an overpotential of only 265 mV for
      half activity at low acid concentrations. Furthermore, catalysis is possible
      using a weak acid, and the complex is stable for at least 4 h in acidic solution.
      Calculations of the system carried out at the density functional level of theory
      (DFT) are consistent with a mechanism for catalysis in which both protonations
      take place at the nickel center. 

PMID- 25562524
TI  - One-step synthesis of amine-functionalized hollow mesoporous silica nanoparticles
      as efficient antibacterial and anticancer materials.
AB  - In this study, amine-functionalized hollow mesoporous silica nanoparticles with
      an average diameter of ~100 nm and shell thickness of ~20 nm were prepared by an
      one-step process. This new nanoparticulate system exhibited excellent killing
      efficiency against mycobacterial (M. smegmatis strain mc(2) 651) and cancer cells
      (A549). 

PMID- 25562525
TI  - Implications of the circumpolar genetic structure of polar bears for their
      conservation in a rapidly warming Arctic.
AB  - We provide an expansive analysis of polar bear (Ursus maritimus) circumpolar
      genetic variation during the last two decades of decline in their sea-ice
      habitat. We sought to evaluate whether their genetic diversity and structure have
      changed over this period of habitat decline, how their current genetic patterns
      compare with past patterns, and how genetic demography changed with ancient
      fluctuations in climate. Characterizing their circumpolar genetic structure using
      microsatellite data, we defined four clusters that largely correspond to current
      ecological and oceanographic factors: Eastern Polar Basin, Western Polar Basin,
      Canadian Archipelago and Southern Canada. We document evidence for recent (ca.
      last 1-3 generations) directional gene flow from Southern Canada and the Eastern
      Polar Basin towards the Canadian Archipelago, an area hypothesized to be a future
      refugium for polar bears as climate-induced habitat decline continues. Our data
      provide empirical evidence in support of this hypothesis. The direction of
      current gene flow differs from earlier patterns of gene flow in the Holocene.
      From analyses of mitochondrial DNA, the Canadian Archipelago cluster and the
      Barents Sea subpopulation within the Eastern Polar Basin cluster did not show
      signals of population expansion, suggesting these areas may have served also as
      past interglacial refugia. Mismatch analyses of mitochondrial DNA data from polar
      and the paraphyletic brown bear (U. arctos) uncovered offset signals in timing of
      population expansion between the two species, that are attributed to differential
      demographic responses to past climate cycling. Mitogenomic structure of polar
      bears was shallow and developed recently, in contrast to the multiple clades of
      brown bears. We found no genetic signatures of recent hybridization between the
      species in our large, circumpolar sample, suggesting that recently observed
      hybrids represent localized events. Documenting changes in subpopulation
      connectivity will allow polar nations to proactively adjust conservation actions
      to continuing decline in sea-ice habitat. 

PMID- 25562528
TI  - Age-related hypertension and salt sensitivity are associated with unique cortico
      medullary distribution of D1R, AT1R, and NADPH-oxidase in FBN rats.
AB  - We examined effects of normal (NS) and high salt (HS) on blood pressure (BP) and
      cortico-medullary distribution of dopamine D1 receptor (D1R), angiotensin AT1
      receptor (AT1R), NADPH oxidase-gp(91phox), and sodium transporters (NHE-3, Na, K
      ATPase) in adult and aged rats. Aged rats fed with NS diet had higher BP, which
      further increased with HS. HS increased D1R mRNA and protein levels in cortex and
      medulla of adult rats. NS or HS fed-aged rats had higher AT1R and gp(91phox) mRNA
      levels in cortex and medulla. Aged rats fed with NS diet had higher gp(91phox)
      protein levels in cortex. HS diet increased AT1R and gp(91phox) protein levels in
      medulla of aged rats. Aged rats fed with NS or HS diet had higher NHE-3 protein
      levels in medulla. HS increased Na, K ATPase protein levels in medulla of aged
      rats. HS increased urinary kidney injury molecule-1 (KIM-1) but not protein or
      albumin levels in aged rats. These results suggest that cortical gp(91phox) and
      medullary NHE-3 contribute to age-related hypertension. Whereas D1R (cortical and
      medullary) together with medullary AT1R, gp(91phox) and Na, K-ATPase contribute
      to salt sensitivity in aged rats. And, KIM-1 may be a better marker for kidney
      damage.

PMID- 25562526
TI  - A new framework for cortico-striatal plasticity: behavioural theory meets in
      vitro data at the reinforcement-action interface.
AB  - Operant learning requires that reinforcement signals interact with action
      representations at a suitable neural interface. Much evidence suggests that this
      occurs when phasic dopamine, acting as a reinforcement prediction error, gates
      plasticity at cortico-striatal synapses, and thereby changes the future
      likelihood of selecting the action(s) coded by striatal neurons. But this
      hypothesis faces serious challenges. First, cortico-striatal plasticity is
      inexplicably complex, depending on spike timing, dopamine level, and dopamine
      receptor type. Second, there is a credit assignment problem-action selection
      signals occur long before the consequent dopamine reinforcement signal. Third,
      the two types of striatal output neuron have apparently opposite effects on
      action selection. Whether these factors rule out the interface hypothesis and how
      they interact to produce reinforcement learning is unknown. We present a
      computational framework that addresses these challenges. We first predict the
      expected activity changes over an operant task for both types of action-coding
      striatal neuron, and show they co-operate to promote action selection in learning
      and compete to promote action suppression in extinction. Separately, we derive a
      complete model of dopamine and spike-timing dependent cortico-striatal plasticity
      from in vitro data. We then show this model produces the predicted activity
      changes necessary for learning and extinction in an operant task, a remarkable
      convergence of a bottom-up data-driven plasticity model with the top-down
      behavioural requirements of learning theory. Moreover, we show the complex
      dependencies of cortico-striatal plasticity are not only sufficient but necessary
      for learning and extinction. Validating the model, we show it can account for
      behavioural data describing extinction, renewal, and reacquisition, and replicate
      in vitro experimental data on cortico-striatal plasticity. By bridging the levels
      between the single synapse and behaviour, our model shows how striatum acts as
      the action-reinforcement interface. 

PMID- 25562530
TI  - Simultaneous detection of polar and nonpolar compounds by ambient mass
      spectrometry with a dual electrospray and atmospheric pressure chemical
      ionization source.
AB  - A dual ionization source combining electrospray ionization (ESI) and atmospheric
      pressure chemical ionization (APCI) was developed to simultaneously ionize both
      polar and nonpolar compounds. The source was constructed by inserting a fused
      silica capillary into a stainless steel column enclosed in a glass tube. A high
      dc voltage was applied to a methanol solution flowing in the fused silica
      capillary to generate an ESI plume at the capillary tip. A high ac voltage was
      applied to a ring electrode attached to the glass tube to generate plasma from
      the nitrogen gas flowing between the glass tube and the stainless steel column.
      The concentric arrangement of the ESI plume and the APCI plasma in the source
      ensured that analytes entering the ionization region interacted with both ESI and
      APCI primary ion species generated in the source. Because the high voltages
      required for ESI and APCI were independently applied and controlled, the dual ion
      source could be operated in ESI-only, APCI-only, or ESI+APCI modes. Analytes were
      introduced into the ESI and/or APCI plumes by irradiating sample surfaces with a
      continuous-wavelength laser or a pulsed laser beam. Analyte ions could also be
      produced by directing the dual ESI+APCI source toward sample surfaces for
      desorption and ionization. The ionization mechanisms involved in the dual ion
      source include Penning ionization, ion molecule reactions, and fused-droplet
      electrospray ionization. Standards of polycyclic aromatic hydrocarbons,
      angiotensin I, lidocaine, ferrocene, diesel, and rosemary oils were used for
      testing. Protonated analyte ions were detected in ESI-only mode, radical cations
      were detected in APCI-only mode, and both types of ions were detected in ESI+APCI
      mode. 

PMID- 25562527
TI  - Mitochondria-associated microRNAs in rat hippocampus following traumatic brain
      injury.
AB  - Traumatic brain injury (TBI) is a major cause of death and disability. However,
      the molecular events contributing to the pathogenesis are not well understood.
      Mitochondria serve as the powerhouse of cells, respond to cellular demands and
      stressors, and play an essential role in cell signaling, differentiation, and
      survival. There is clear evidence of compromised mitochondrial function following
      TBI; however, the underlying mechanisms and consequences are not clear. MicroRNAs
      (miRNAs) are small non-coding RNA molecules that regulate gene expression post
      transcriptionally, and function as important mediators of neuronal development,
      synaptic plasticity, and neurodegeneration. Several miRNAs show altered
      expression following TBI; however, the relevance of mitochondria in these
      pathways is unknown. Here, we present evidence supporting the association of
      miRNA with hippocampal mitochondria, as well as changes in mitochondria
      associated miRNA expression following a controlled cortical impact (CCI) injury
      in rats. Specifically, we found that the miRNA processing proteins Argonaute
      (AGO) and Dicer are present in mitochondria fractions from uninjured rat
      hippocampus, and immunoprecipitation of AGO associated miRNA from mitochondria
      suggests the presence of functional RNA-induced silencing complexes.
      Interestingly, RT-qPCR miRNA array studies revealed that a subset of miRNA is
      enriched in mitochondria relative to cytoplasm. At 12h following CCI, several
      miRNAs are significantly altered in hippocampal mitochondria and cytoplasm. In
      addition, levels of miR-155 and miR-223, both of which play a role in
      inflammatory processes, are significantly elevated in both cytoplasm and
      mitochondria. We propose that mitochondria-associated miRNAs may play an
      important role in regulating the response to TBI. 

PMID- 25562529
TI  - Fasting glucose and glucose tolerance as potential predictors of neurocognitive
      function among nondiabetic older adults.
AB  - INTRODUCTION: Significant evidence has demonstrated that Type 2 diabetes mellitus
      and related precursors are associated with diminished neurocognitive function and
      risk of dementia among older adults. However, very little research has examined
      relations of glucose regulation to neurocognitive function among older adults
      free of these conditions. The primary aim of this investigation was to examine
      associations among fasting glucose, glucose tolerance, and neurocognitive
      function among nondiabetic older adults. The secondary aim was to examine age,
      gender, and education as potential effect modifiers. METHOD: The study employed a
      cross-sectional, correlational study design. Participants were 172 older adults
      with a mean age of 64.43 years (SD = 13.09). The sample was 58% male and 87%
      White. Participants completed an oral glucose tolerance test as part of a larger
      study. Trained psychometricians administered neuropsychological tests that
      assessed performance in the domains of response inhibition, nonverbal memory,
      verbal memory, attention and working memory, visuoconstructional abilities,
      visuospatial abilities, psychomotor speed and executive function, and motor speed
      and manual dexterity. Linear multiple regressions were run to test study aims.
      RESULTS: No significant main effects of fasting glucose and 2-hour glucose
      emerged for performance on any neurocognitive test; however, significant
      interactions were present. Higher fasting glucose was associated with poorer
      short-term verbal memory performance among men, but unexpectedly better response
      inhibition and long-term verbal memory performance for participants over age 70.
      Higher 2-hour glucose values were associated with reduced divided attention
      performance among participants with less than a high school education.
      CONCLUSIONS: Mixed findings suggest that glucose levels may be both beneficial
      and deleterious to neurocognition among nondiabetic older adults. Additional
      studies with healthy older adults are needed to confirm this unexpected pattern
      of associations; however, findings have implications for the importance of
      maintaining healthy glucose levels in older adulthood.

PMID- 25562531
TI  - Validation of a Dutch Version of the Reproductive Concerns Scale (RCS) in Three
      Populations of Women.
AB  - We investigated the psychometric properties of a Dutch version of the
      Reproductive Concerns Scale (RCS). Questionnaires (N = 515) were administered to
      90 women with breast cancer, 227 women with fertility problems, and 198 healthy
      controls. Principal axis factor analysis suggested a one-factor structure with 11
      items (breast cancer patients R(2) =.48, alpha =.87, ICC =.95; women with
      fertility problems R(2) =.45, alpha =.89, ICC =.86). Women with fertility
      problems reported the most concerns (M = 21.8, SD = 9.6), followed by breast
      cancer patients (M = 14.8, SD = 10.0) and healthy controls (M = 6.4, SD = 7.0).
      Theoretically related constructs were correlated to the RCS (.33 < r >.73). The
      RCS seems to be a valid tool for assessing women's reproductive concerns. 

PMID- 25562534
TI  - Is oral absorption of vigabatrin carrier-mediated?
AB  - The aim of the study was to investigate the intestinal transport mechanisms
      responsible for vigabatrin absorption in rats by developing a population
      pharmacokinetic (PK) model of vigabatrin oral absorption. The PK model was used
      to investigate whether vigabatrin absorption was carrier-mediated and if the
      proton-coupled amino acid transporter 1 (PAT1) was involved in the absorption
      processes. Vigabatrin (0.3-300mg/kg) was administered orally or intravenously to
      Sprague Dawley rats in the absence or presence of PAT1-ligands l-proline, l
      tryptophan or sarcosine. The PK profiles of vigabatrin were described by
      mechanistic non-linear mixed effects modelling, evaluating PAT1-ligands as
      covariates on the PK parameters with a full covariate modelling approach. The
      oral absorption of vigabatrin was adequately described by a Michaelis-Menten type
      saturable absorption. Using a Michaelis constant of 32.8mM, the model estimated a
      maximal oral absorption rate (Vmax) of 64.6mmol/min and dose-dependent
      bioavailability with a maximum of 60.9%. Bioavailability was 58.5-60.8% at 0.3
      30mg/kg doses, but decreased to 46.8% at 300mg/kg. Changes in oral vigabatrin PK
      after co-administration with PAT1-ligands was explained by significant increases
      in the apparent Michaelis constant. Based on the mechanistic model, a high
      capacity low affinity carrier is proposed to be involved in intestinal vigabatrin
      absorption. PAT1-ligands increased the Michaelis constant of vigabatrin after
      oral co-administration indicating that this carrier could be PAT1. 

PMID- 25562532
TI  - The tumor-targeting immunocytokine F16-IL2 in combination with doxorubicin: dose
      escalation in patients with advanced solid tumors and expansion into patients
      with metastatic breast cancer.
AB  - A phase Ib/II trial was performed to evaluate safety, tolerability, recommended
      dose (RD) and efficacy of F16-IL2, a recombinant antibody-cytokine fusion
      protein, in combination with doxorubicin in patients with solid tumors (phase Ib)
      and metastatic breast cancer (phase II). Six patient cohorts with progressive
      solid tumors (n = 19) received escalating doses of F16-IL2 [5-25 Million
      International Units (MIU) of IL2 equivalent dose] in combination with escalating
      doses of doxorubicin (0-25 mg/m(2)) on day 1, 8 and 15 every 4 weeks.
      Subsequently, patients with metastatic breast cancer (n = 10) received the drug
      combination at the RD. Clinical data and laboratory findings were analyzed for
      safety, tolerability, and activity. F16-IL2 could be administered up to 25 MIU,
      in combination with the RD of doxorubicin (25 mg/m(2)). No human anti-fusion
      protein antibodies (HAFA) response was detected. Pharmacokinetics of F16-IL2 was
      dose-dependent over the tested range, with half-lives of ca. 13 and ca. 8 hours
      for cohorts dosed at lower and higher levels, respectively. Toxicities were
      controllable and reversible, with no combination treatment-related death. After 8
      weeks, 57% and 67% disease control rates were observed for Phase I and II,
      respectively (decreasing to 43% and 33% after 12 weeks), considering 14 and 9
      patients evaluable for efficacy. One patient experienced a long lasting partial
      response (45 weeks), still on-going at exit of study. F16-IL2 can be safely and
      repeatedly administered at the RD of 25 MIU in combination with 25 mg/m(2)
      doxorubicin; its safety and activity are currently being investigated in
      combination with other chemotherapeutics, in order to establish optimal therapy
      settings.

PMID- 25562536
TI  - Emotional Functioning in Obsessive-Compulsive Personality Disorder: Comparison to
      Borderline Personality Disorder and Healthy Controls.
AB  - Few studies have investigated emotional functioning in obsessive-compulsive
      personality disorder (OCPD). To explore the nature and extent of emotion
      difficulties in OCPD, the authors examined four domains of self-reported
      emotional functioning--negative affectivity, anger, emotion regulation, and
      emotion expressivity--in women with OCPD and compared them to a borderline
      personality disorder (BPD) group and a healthy control group. Data were collected
      as part of a larger psychophysiological experimental study on emotion regulation
      and personality. Compared to healthy controls, participants with OCPD reported
      significantly higher levels of negative affectivity, trait anger, emotional
      intensity, and emotion regulation difficulties. Emotion regulation difficulties
      included lack of emotional clarity, nonacceptance of emotional responses, and
      limited access to effective emotion regulation strategies. Participants with OCPD
      scored similarly to participants with BPD on only one variable, namely, problems
      engaging in goal-directed behavior when upset. Results suggest that OCPD may be
      characterized by notable difficulties in several emotional domains.

PMID- 25562535
TI  - Gender Differences in Borderline Personality Disorder: Results From a
      Multinational, Clinical Trial Sample.
AB  - This study aims to extend previous research by considering gender differences in
      borderline personality (BPD) using both dimensional self-reported and clinical
      measures of symptomatology. Drawing from a cross-cultural, clinical trial sample,
      the authors compared female and male BPD subjects (N = 770; 211 male) between the
      ages of 18 and 65 using diagnostic and self-report data. The authors found that
      women with BPD have greater hostility and relationship disruption than men.
      Gender differences in eating disorders, particularly bulimia, are more divergent
      than in the general population. Generally, gender differences in BPD in this
      sample are consistent with known general population differences. Women show
      greater overall symptomatology, including depressive, anxious, and somatic
      symptoms. Men have higher rates of antisocial personality disorder and a trend
      toward higher rates of narcissistic personality disorder. However, several gender
      differences consistently found in the general population are not present in this
      BPD sample. There are no differences in aggression, suicidality, substance abuse,
      panic disorder, or obsessive-compulsive disorder. Gender differences in major
      depression and posttraumatic stress disorder are attenuated. These findings
      support the conclusion that BPD may diminish normal gender differences. 

PMID- 25562533
TI  - Iron oxide decorated MoS2 nanosheets with double PEGylation for chelator-free
      radiolabeling and multimodal imaging guided photothermal therapy.
AB  - Theranostics for in vivo cancer diagnosis and treatment generally requires well
      designed nanoscale platforms with multiple integrated functionalities. In this
      study, we uncover that functionalized iron oxide nanoparticles (IONPs) could be
      self-assembled on the surface of two-dimensional MoS2 nanosheets via sulfur
      chemistry, forming MoS2-IO nanocomposites, which are then modified with two types
      of polyethylene glycol (PEG) to acquire enhanced stability in physiological
      environments. Interestingly, (64)Cu, a commonly used positron-emitting
      radioisotope, could be firmly adsorbed on the surface of MoS2 without the need of
      chelating molecules, to enable in vivo positron emission tomography (PET)
      imaging. On the other hand, the strong near-infrared (NIR) and superparamagnetism
      of MoS2-IO-PEG could also be utilized for photoacoustic tomography (PAT) and
      magnetic resonance (MR) imaging, respectively. Under the guidance by such triple
      modal imaging, which uncovers efficient tumor retention of MoS2-IO-(d)PEG upon
      intravenous injection, in vivo photothermal therapy is finally conducted,
      achieving effective tumor ablation in an animal tumor model. Our study highlights
      the promise of constructing multifunctional theranostic nanocomposites based on
      2D transitional metal dichalcogenides for multimodal imaging-guided cancer
      therapy. 

PMID- 25562537
TI  - Links Among High EPDS Scores, State of Mind Regarding Attachment, and Symptoms of
      Personality Disorder.
AB  - Underlying persistent psychological difficulties have been found to moderate
      potential adverse effects of maternal postpartum depression (PPD) on parenting
      and infant development. The authors examined whether mothers presenting
      postpartum depressive symptoms showed higher levels of personality pathology and
      more insecure state of mind regarding attachment compared to nondepressed
      mothers. Participants (N = 85) were assessed with the Edinburgh Postnatal
      Depression Scale (EPDS), the Present State Examination, the Adult Attachment
      Interview, and the Structured Clinical Interview for DSM-IV Axis II. Mothers with
      high EPDS scores were more likely to have a preoccupied insecure state of mind
      and to have personality disorder compared with mothers scoring below clinical
      cutoff. Furthermore, multiple regression analysis showed that personality
      disorder and AAI classification were independently related to EPDS score, and
      that these two factors together accounted for 48% of the variance in EPDS score.
      Findings are discussed in terms of heterogeneity in PPD populations and underline
      the importance of examining potential coexisting psychological difficulties when
      studying PPD. 

PMID- 25562540
TI  - The Relationship Between Psychopathology and a Hierarchical Model of Normal
      Personality Traits: Evidence From a Psychiatric Patient Sample.
AB  - Shifts in the conceptualization of psychopathology have favored a dimensional
      approach, with the five-factor model (FFM) playing a prominent role in this
      research. However, reservations about the utility of the FFM in differentiating
      disorders have risen. In the current investigation, a "bottom-up" analytical
      method was used to ascertain the hierarchical structure of personality, with
      investigation of the specificity of the traits in categorizing diagnostic
      categories across an expanded array of psychiatric disorders. Following earlier
      investigations, which used a hierarchical structural approach, this study
      presents new results relating to the differentiation of several forms of
      psychopathology not included in these earlier analyses--bipolar disorder,
      psychotic disorders, problem gambling, posttraumatic stress disorder, and
      somatoform disorders--across distinct levels of a personality hierarchy based on
      the FFM. These results bolster the argument for the use of FFM personality traits
      in characterizing and differentiating psychiatric diagnostic groups.

PMID- 25562538
TI  - Unidirectionality Between Borderline Personality Disorder Traits and
      Psychopathology in a Residential Addictions Sample: A Short-Term Longitudinal
      Study.
AB  - Borderline personality disorder (BPD) is a barrier to treatment, yet the
      relationship between BPD features and other psychopathology symptoms in
      residential addictions treatment samples is understudied. Using a sample of
      adults enrolled in a residential drug treatment facility measured at baseline and
      2-3 month follow-up, the authors examined the prospective relationship between
      BPD features and five indices of psychopathology: depression, anxiety,
      interpersonal sensitivity, hostility, and psychoticism, as well as
      psychopathology global severity. There was no effect of time on any of the forms
      of psychopathology, but females reported higher levels of BPD features, anxiety
      symptoms, and interpersonal sensitivity than males. A series of latent change
      score models indicated that BPD features predicted increases in all
      psychopathology scales at follow-up, while the reverse was not true. These
      results suggest that targeting BPD features in residents of drug treatment
      facilities may reduce the emergence of new psychopathology in the short term. 

PMID- 25562539
TI  - Personality Pathology and Interpersonal Problem Stability.
AB  - Personality disorders (PDs) are often described as stable, which ignores the
      important dynamic processes and shifts that are observed clinically in
      individuals with PD. The current study examined patterns of variability in
      problematic interpersonal functioning, a core feature of personality pathology.
      Participants (N = 150) were assessed for personality pathology at baseline and
      also completed the Inventory of Interpersonal Problems-Circumplex Scales at
      baseline and every 3 months over the course of a year. Baseline PD was used to
      predict individual means and variability parameters in generalized interpersonal
      distress, agentic problems, and communal problems across repeated assessments.
      Disorders associated with disinhibition predicted variability in generalized
      distress and agentic problems, whereas only antagonism-related disorders
      predicted variability in communal problems. These associations reveal dynamic
      processes involved in multiple dimensions of personality pathology and suggest
      that future research on instability is needed that expands beyond the historical
      focus on borderline PD. 

PMID- 25562541
TI  - A guanine-ethylthioethyl-glutathione adduct as a major DNA lesion in the skin and
      in organs of mice exposed to sulfur mustard.
AB  - Sulfur mustard (SM) is an old chemical warfare but it remains a threat to both
      militaries and civilians. SM mainly targets skin, eyes and lungs and diffuses to
      internal organs. At the molecular level, SM is able to damage DNA through the
      formation of monoadducts and biadduct. Glutathione (GSH) is another critical
      target of SM in cells since it is part of the detoxification mechanism against
      alkylating agents. In the present work, we investigated whether SM could form
      covalent bonds simultaneously with a DNA base and the sulfhydryl group of GSH.
      The expected guanine adduct, S-[2-(N7-guanyl)-ethylthioethyl]-glutathione (N7Gua
      ETE-GSH), was synthesized and detected in several tissues of SKH-1 mice exposed
      to 60mg/kg of SM in the dorsal-lumbar region. N7Gua-ETE-GSH was detected in all
      organs studied, except in the liver. The tissue exhibiting the highest levels of
      N7Gua-ETE-GSH was skin, followed by brain, lungs, kidneys and spleen. N7Gua-ETE
      GSH was detected in skin, brain and lungs as long as two weeks after exposure.
      The persistence was less in other organs. The observation of the formation of
      N7Gua-ETE-GSH in vivo confirms the variety of damages induced by SM in DNA. It
      also provides another example of the formation of DNA adducts involving
      glutathione following in vivo exposure to bifunctional alkylating compounds. 

PMID- 25562542
TI  - The effectiveness of oxygen therapy in carbon monoxide poisoning is pressure- and
      time-dependent: a study on cultured astrocytes.
AB  - Carbon monoxide (CO) poisoning causes neuronal and glial apoptosis that can
      result in delayed neurological symptoms. The damage of brain cells can be
      prevented by oxygen therapy. Based on the central role of astrocytes in
      maintaining neuronal function and viability we investigated the toxic effects of
      3000ppm CO in air followed by 24h of normoxia and evaluated the possible
      protective influence of 100% normobaric oxygen or 100% oxygen at a pressure of
      3bar (hyperbaric) against CO poisoning in these cells. CO/normoxia caused a
      progressive decline of viability, increase in reactive oxygen species and decline
      of mitochondrial membrane potential and intracellular ATP levels in cultured rat
      astrocytes. Increased caspase-9, caspase-8 and calpain activity converged in
      activation of caspase-3/7. 1h treatment with oxygen disclosed pressure- and time
      dependent efficacy in restoring astrocytic mitochondrial function and the
      prevention of apoptosis. The protective effect was most evident when the
      astrocytes were exposed to hyperbaric oxygen, but not normobaric oxygen, 1-5h
      after exposure to CO. 

PMID- 25562543
TI  - Influence of genetic polymorphisms of styrene-metabolizing enzymes on the levels
      of urinary biomarkers of styrene exposure.
AB  - Styrene exposure is still present in different occupational settings including
      manufacture of synthetic rubber, resins, polyesters and plastic. The aim of this
      work was to investigate the effects of polymorphic genes CYP2E1, EPHX1, GSTT1,
      and GSTM1 on the urinary concentrations of the styrene metabolites mandelic acid
      (MA), phenylglyoxylic acid (PGA) and on the concentration ratios between (MA+PGA)
      and urinary styrene (U-Sty) and airborne styrene (A-Sty), in 30 workers from two
      fiberglass-reinforced plastic manufacturing plants and 26 unexposed controls.
      Personal air sampling and biological monitoring results revealed that sometimes
      exposure levels exceeded both the threshold limit value (TLV) and the biological
      exposure index (BEI) suggested by the American Conference of Governmental
      Industrial Hygienists. A significantly reduced excretion of styrene metabolites
      (MA+PGA) in individuals carrying the CYP2E1*5B and CYP2E1*6 heterozygote alleles,
      with respect to the homozygote wild type, was observed only in the exposed group.
      A reduction was also detected, in the same group, in subjects carrying the slow
      allele EPHX1 (codon 113), through the lowering of (MA+PGA)/urinary styrene
      concentration ratio. In addition, the ratio between MA+PGA and the personal
      airborne styrene concentration appeared to be modulated by the predicted mEH
      activity, in the exposed group, as evidenced by univariate linear regression
      analysis. Our results confirm some previous hypotheses about the role of the
      polymorphism of genes coding for enzymes involved in the styrene detoxification
      pathway: this may significantly reduce the levels of excreted metabolites and
      therefore it must be taken into account in the interpretation of the biological
      monitoring results for occupational exposure. 

PMID- 25562546
TI  - Whole Lyophilized Olives as Sources of Unexpectedly High Amounts of Secoiridoids:
      The Case of Three Tuscan Cultivars.
AB  - The phenolic profiles of three typical Tuscan olive cultivars, Frantoio,
      Moraiolo, and Leccino, stored in different conditions (fresh, frozen, and whole
      lyophilized fruits), have been compared during the ripening period. Our main
      goals were to evaluate the phenolic content of whole freeze-dried fruits and to
      test the stability of the corresponding cake in oxidative-stress conditions. The
      comparison of fresh and whole freeze-dried fruits from the 2012 season gave
      unexpected results; e.g., oleuropein in lyophilized fruits was up to 20 times
      higher than in fresh olives with values up to 80.3 g/kg. Over time we noted that
      the olive pastes obtained from lyophilized olives contained highly stable
      phenolic compounds, even under strong oxidative stress conditions. Finally, it
      was also observed that the cake/powder obtained from unripe freeze-dried olives
      was very poor in oil content and therefore quite suitable for use in nutritional
      supplements rich in phenolic compounds, such as secoiridoids, which are not
      widely present in the human diet.

PMID- 25562544
TI  - In vitro evaluation of neurotoxicity potential and oxidative stress responses of
      diazinon and its degradation products in rat brain synaptosomes.
AB  - Although primary toxic action of organophosphorous insecticides is associated
      with acetylcholinesterase inhibition, later studies suggest that oxidative stress
      may be responsible for induced organophosphates toxicity. These studies mostly
      include thio forms, while the effects of their metabolites/degradation products
      have been less investigated. Therefore, this paper studies the toxic effects of
      diazinon degradation products, diazoxon and 2-isopropyl-6-methyl-4-pyrimidinol,
      and compares them with the toxic potential of the parent compound. The toxicity
      induced by various concentrations of the investigated compounds was in vitro
      evaluated by the activities of acetylcholinesterase, ATPases, antioxidant defense
      enzymes and lactate dehydrogenase, and malondialdehyde level in rat brain
      synaptosomes. Diazinon inhibited acetylcholinesterase and Na(+)/K(+)-ATPase in
      dose-dependent manner, while the inhibition of ecto-ATPase activity was less than
      15% at all investigated concentrations. It did not demonstrate noteworthy
      prooxidative properties causing increase (up to 10%) in antioxidant enzymes
      activity and malondialdehyde level, as a marker of lipid peroxidation. Diazinon
      oxidation product, diazoxon was found as the most toxic investigated compound.
      Beside the expected strong inhibitory effect on acetylcholinesterase, it induced
      dose-dependent and almost complete inhibition of Na(+)/K(+)-ATPase and ecto
      ATPase at the highest investigated concentration (0.1mM). Increasing diazoxon
      concentrations activated catalase (up to 30%), superoxide dismutase (up to 50%),
      glutathione peroxidase (up to 30%), and significantly increased malondialdehyde
      level (up to 50%). The investigated hydrolysis product of diazinon, 2-isopropyl-6
      methyl-4-pyrimidinol did not remarkably alter the activities of
      acetylcholinesterase, Na(+)/K(+)-ATPase, catalase, glutathione peroxidase and
      lipid peroxidation level (up to about 10%). Although this diazinon metabolite has
      been known as non toxic, it induced superoxide dismutase stimulation up to 30%.
      Finally, even high concentrations of both diazinon and its metabolites did
      noticeably affect lactate dehydrogenase activity as a marker of synaptosomal
      integrity. The changes in investigated biochemical parameters in rat brain
      synaptosomes could serve as indicators of toxicity due to the exposure to thio
      organophosphates and/or their break-down products. 

PMID- 25562547
TI  - FeNO as biomarker for asthma phenotyping and management.
AB  - The current review aims to revisit literature on exhaled nitric oxide (FeNO) in
      asthma phenotyping and management to clarify the utility of this test in clinical
      practice. It is increasingly evident that multiple profiles characterize asthma
      as a complex disease for which is necessary to find tools able to discriminate
      among these phenotypes to achieve the best therapeutic strategy for all asthmatic
      patients. Current findings indicate that FeNO, a noninvasive and easy-to-obtain
      biomarker, can be considered a useful tool in predicting asthma developing and
      exacerbation, in identifying specific asthma phenotypes, in improving asthma
      diagnosis and management in a selected population, and in monitoring efficacy of
      standard corticosteroid and biologic therapy. Based on this evidence, FeNO might
      become an appropriate tool for physicians to better define specific asthma
      phenotypes and to better deal with asthma worsening. 

PMID- 25562545
TI  - Predictors of major improvement after intravenous thrombolysis in acute ischemic
      stroke.
AB  - BACKGROUND: Intravenous thrombolysis improves outcomes of stroke patients. The
      immediate response to thrombolysis is variable and few studies attempted to
      identify predictors of major neurological improvement (MNI) 24 h following
      thrombolysis. Our objective is to determine predictors of MNI 24 h following
      thrombolysis. METHODS: We reviewed the prospective database of patients treated
      through our telestroke network and at our institution between November 2008 and
      June 2012. We included all patients who received IV t-PA and had a 24-h NIHSS
      score available. Similar to previous studies, we defined MNI as a reduction in
      NIHSS score by >=8 points, or a score of 0 or 1 at 24 h. Demographics, risk
      factors, time to treatment, and clinical and laboratory data, were compared
      between MNI present or absent. Baseline predictors were compared using t- and
      Fisher's exact tests, and outcomes using multivariate logistic regression
      analysis. RESULTS: Out of 316 patients, 306 had 24-h NIHSS scores and 38% of them
      experienced MNI. Patients with MNI were less likely to be older than 80 years
      (16% vs. 29%, p = 0.008) and to have atrial fibrillation (9% vs. 24%, p = 0.001)
      compared to those without; we found no other predictors of MNI. After adjusting
      for baseline demographics and risk factors, age less than 80 years (OR = 1.9, 95%
      CI 1.1-3.6) and absence of atrial fibrillation (OR = 3.0, 95% CI: 1.4-6.2)
      predicted MNI. CONCLUSION: Major neurological improvement within 24 h after
      thrombolysis is more likely in younger patients and those without atrial
      fibrillation.

PMID- 25562548
TI  - The asthma-chronic obstructive pulmonary disease overlap syndrome and its
      challenge for the allergist-immunologist.

PMID- 25562549
TI  - Burden of chronic obstructive pulmonary disease: healthcare costs and beyond.
AB  - Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating
      respiratory condition that leads to significant burden, both medically and
      financially. It affects millions of people worldwide and causes significant
      morbidity and mortality. Most detailed information related to its prevalence,
      morbidity, and mortality comes from high-income countries, but 90% of COPD
      related deaths occur in low- and middle-income countries. Cigarette smoking is
      the main risk factor for developing COPD, but other risk factors do exist and
      need to be recognized. A majority of morbidity and mortality as well as health
      care costs occur from acute exacerbations of COPD with a known phenotype of
      patients being "frequent exacerbators." Health care costs for COPD are not only
      from treatment of exacerbations, such as hospitalization, but also medication
      costs for maintenance therapy and outpatient treatment. COPD has been linked with
      many comorbidities leading to significant burden of disease. The goal of this
      review is to evaluate the overall burden of disease including prevalence,
      morbidity, mortality, health care costs, and economic costs. 

PMID- 25562550
TI  - Oxidative stress markers in patients with hymenoptera venom allergy.
AB  - Oxidative stress occurs in many allergic and immunologic disorders as a result of
      the imbalance between the endogenous production of free reactive oxygen species
      (ROS) and/or the reduction of antioxidant defense mechanisms. Advanced glycation
      end products (AGEs), advanced oxidation protein products (AOPPs), and
      nitrosylated proteins (NPs) can be used as markers of oxidative stress and
      inflammation. Our objective was to examine the serum levels of AGEs, AOPPs, and
      NPs in patients with allergic reactions to hymenoptera venom before and after
      ultrarush venom immunotherapy (VIT). The study included two groups of patients:
      30 patients allergic to yellow jacket or honey bee venom and treated by aqueous
      preparation of Vespula spp (26 patients) or Apis mellifera (four patients) VIT,
      and 30 healthy donors as controls. Blood samples were collected to measure serum
      levels of AGEs, AOPPs, and NPs at baseline (T1), at the end of the incremental
      phase of the VIT protocol (T2), and after 15 days (T3). Serum AOPP levels at T1
      were significantly higher in comparison with controls (p = 0.001), whereas serum
      levels of NPs at T1 were significantly lower than those in controls (p < 0.0001).
      No significant difference in circulating levels of AOPPs, AGEs, and NPs was found
      during immunotherapy. These findings suggest that, although hymenoptera venom
      allergy (HVA) is characterized by isolated episodes of reactions to stinging
      insect venom and is not included among chronic inflammatory diseases, an
      oxidative stress status occurs in patients suffering from this kind of allergy.
      Furthermore, VIT does not modify serum levels of these oxidative stress
      biomarkers. 

PMID- 25562551
TI  - The chronic obstructive pulmonary disease-asthma overlap syndrome.
AB  - When asthma and chronic obstructive pulmonary disease (COPD) occur together the
      term COPD-asthma overlap syndrome has been applied. To date, there is no
      universally accepted definition of this overlap syndrome, just as there is no
      blood test or other technologic assessment that provides a simple way to
      distinguish asthma from COPD. One practical approach to the overlap diagnosis has
      been to include patients with a diagnosis of COPD by Global Initiative for
      Chronic Obstructive Lung Disease criteria and asthma defined by subject report of
      a physician diagnosis of asthma before the age of 40 years. Alternatively, it
      includes patients who meet criteria for COPD (fixed airflow obstruction) and who
      also have typical features of asthma (wheezing, atopy, eosinophilia, and positive
      bronchodilator response on spirometry). Compared with patients with COPD alone,
      the overlap patients are younger with less smoking intensity, have higher health
      care utilization, have a worse disease-related quality of life, and have a higher
      mortality. Treatment with corticosteroids earlier in the course of the disease
      compared with the patient with only COPD has been recommended. 

PMID- 25562552
TI  - Microorganism-induced exacerbations in atopic dermatitis: a possible preventive
      role for vitamin D?
AB  - Atopic dermatitis (AD) is a common skin disease characterized by a complex
      pathogenesis not completely understood despite numerous studies to date. The
      clinical patterns result from interactions between genetic disorders determining
      abnormalities in the epidermis differentiation complex, modification of the
      cutaneous barrier, and dysfunction of immune responses. Several studies have
      shown that an alteration of the skin barrier combined with immune dysfunction is
      important for the onset, maintenance, and risk of exacerbations of the disease.
      In recent years, new aspects regarding the pathogenesis of the disease, such as
      the effects of vitamin D (VD) on immunity at the skin level and the role of
      certain microorganisms (particularly Staphylococcus and Malassezia species) on
      eczema exacerbations, have been evaluated. This article provides an overview of
      the evidences supporting the link between VD (deficiency) and microorganisms
      (skin colonization/sensitization) in AD pathogenesis, based on comprehensive
      review of the literature. By considering different aspects of disease, it might
      be possible to improve our understanding, particularly in those patients
      refractory to conventional treatments. An electronic research strategy was used
      to search in Medline Pub-Med Library using as research words AD, exacerbation,
      VD, Staphylococcus aureus (SA), and Malassezia. The results were downloaded and
      analyzed for systematic review. Few studies actually consider the relationship
      between VD deficiency (VDD), AD, and SA and Malassezia, but many suggest a
      correlation between these factors. VDs play a major role against microorganisms
      in the development of AD and should be considered when treating patients. 

PMID- 25562553
TI  - A review of the evidence linking eosinophilic esophagitis and food allergy.
AB  - Eosinophilic esophagitis (EoE) is a chronic inflammation of the esophagus that
      has been considered an allergic phenomenon based on its similarities to other
      allergic conditions. More specifically, EoE has been considered a form of food
      allergy because of patient sensitizations to foods and improvements in symptoms
      and inflammation after food eliminations. This article presents the currently
      available evidence regarding the classification of EoE as an allergic condition,
      the involvement of foods in disease pathogenesis, and the value of different
      types of allergy testing and elimination diets in management of EoE. Using the
      search engines PubMed and Ovid, English literature in the past 10 years was
      reviewed with the use of the following key words: eosinophilic esophagitis, EoE
      epidemiology, EoE pathophysiology, food allergy, eosinophils, skin-prick testing,
      atopy patch testing, elemental diet, test directed elimination diet, six food
      elimination diet. Studies of EoE epidemiology and pathophysiology support the
      link between EoE and allergy in general, and studies of food allergy testing and
      elimination diets have supported a link between EoE and food allergy. Although
      food elimination diets cause resolution of symptoms and pathology in pediatric
      EoE, the results of testing and diet elimination studies are not as clear in
      adults, and aeroallergen sensitizations may play a larger role in adult EoE
      pathophysiology. Although several studies in children and adults support
      considering EoE a form of food allergy, the usefulness of skin-prick testing and
      atopy patch testing for food allergies and the optimal elimination diet for
      disease management are still uncertain. 

PMID- 25562554
TI  - Management of patients with nonaspirin-exacerbated respiratory disease aspirin
      hypersensitivity reactions.
AB  - Because of widespread use, nonsteroidal anti-inflammatory drugs (NSAIDs) are the
      second most common cause of all adverse drug reactions, with hypersensitivity
      reported in ~1% of the population. NSAID hypersensitivity can be categorized into
      five types by the underlying disease, symptoms of reaction, and timing of
      reaction. These include rhinitis and asthma induced by NSAIDs (also known as
      aspirin-exacerbated respiratory disease), NSAID-exacerbated cutaneous disease
      (NECD), urticaria or angioedema induced by multiple NSAIDs, single NSAID-induced
      reactions, and delayed NSAID reactions. NECD occurs in one-third of patients with
      chronic urticaria who develop an exacerbation of their urticaria, sometimes with
      angioedema, typically beginning 30-90 minutes after ingestion of NSAIDs that
      inhibit cyclooxygenase (COX)-1. In urticaria or angioedema induced by multiple
      NSAIDs, patients without underlying disease develop urticaria or angioedema 30-90
      minutes after ingestion of COX-1-inhibiting NSAIDs including aspirin. Single
      NSAID-induced reactions are immediate and specific to a single NSAID and are
      thought to occur because of an IgE-mediated reaction against a specific epitope
      of the NSAID. Delayed NSAID reactions occur days to weeks after initiating an
      NSAID. These are T-cell mediated and not amenable to desensitization or
      rechallenge. Classifying the type of NSAID hypersensitivity is important because
      many patients with a prior history of urticaria or angioedema induced by multiple
      NSAIDs will often tolerate aspirin test dose. This would allow the use of an
      aspirin for primary or secondary prevention in patients with coronary artery
      disease despite a presumed history of NSAID hypersensitivity. 

PMID- 25562555
TI  - Effectiveness of MP29-02 for the treatment of allergic rhinitis in real-life:
      results from a noninterventional study.
AB  - The efficacy of MP29-02 (a novel intranasal formulation of azelastine
      hydrochloride and fluticasone propionate in an advanced delivery system) has been
      well established in controlled clinical trials. This study was designed to assess
      the use of MP29-02 and its effectiveness in routine clinical practice. This was a
      German multicenter, prospective, noninterventional study, including 1781 allergic
      rhinitis (AR) patients. Eligible patients (i.e., acute AR symptoms and visual
      analog scale [VAS] score >50 mm) were included, assigned MP29-02 at baseline, and
      reassessed after ~14 days. Patients assessed symptom control using a VAS from 0
      (not at all bothersome) to 100 mm (very bothersome) in the morning before MP29-02
      use, on days 0, 1, 3, and 7 and after ~ 14 days. Patients' perceived levels of
      disease control were assessed on day 3. The Youden index determined patient
      reported VAS score cutoffs on day 3 for "well controlled" and "partly
      controlled." MP29-02 reduced the VAS score from 75.4 mm (SD = 17.2) at baseline
      to 21.3 mm (SD = 18.3) by the last visit, a shift of 54.1 mm (SD = 24.6). One in
      every two patients felt their symptoms were well controlled at day 3. This
      perception of well-controlled symptoms at day 3 corresponded to an optimal VAS
      cutoff of 36 mm. On average, patients treated with MP29-02 crossed this well
      controlled VAS cutoff by last visit. Similar results were found in adolescents,
      adults, and older adults, in those with perennial AR (PAR), seasonal AR (SAR), or
      PAR + SAR and in those with more and less severe disease. MP29-02 provides
      effective and rapid symptom control across all age groups in a real-life setting
      with responder rates higher than those observed in controlled clinical trials,
      supporting MP29-02's position as the drug of choice for the treatment for AR. 

PMID- 25562556
TI  - Regional deposition of mometasone furoate nasal spray suspension in humans.
AB  - Nasal deposition studies can demonstrate whether nasal sprays treating allergic
      rhinitis and polyposis reach the ciliated posterior nasal cavity, where turbinate
      inflammation and other pathology occurs. However, quantifying nasal deposition is
      challenging, because in vitro tests do not correlate to human nasal deposition;
      gamma scintigraphy studies are thus used. For valid data, the radiolabel must
      distribute, as the drug, into different-sized droplets, remain associated with
      the drug in the formulation after administration, and not alter its deposition.
      Some nasal deposition studies have demonstrated this using homogenous solutions.
      However, most commercial nasal sprays are heterogeneous suspensions. Using
      mometasone furoate nasal suspension (MFS), we developed a technique to validate
      radiolabel deposition as a surrogate for nasal cavity drug deposition and
      characterized regional deposition and nasal clearance in humans. Mometasone
      furoate (MF) formulation was spiked with diethylene triamine pentacaetic acid.
      Both unlabeled and radiolabeled formulations (n = 3) were sprayed into a
      regionally divided nasal cast. Drug deposition was quantified by high pressure
      liquid chromatography within each region; radiolabel deposition was determined by
      gamma camera. Healthy subjects (n = 12) were dosed and imaged for six hours.
      Scintigraphic images were coregistered with magnetic resonance imaging scans to
      quantify anterior and posterior nasal cavity deposition and mucociliary
      clearance. The ratio of radiolabel to unlabeled drug was 1.05 in the nasal cast
      and regionally appeared to match, indicating that in vivo radiolabel deposition
      could represent drug deposition. In humans, MFS delivered 86% (9.2) of metered
      dose to the nasal cavity, approximately 60% (9.1) of metered dose to the
      posterior nasal cavity. After 15 minutes, mucociliary clearance removed 59% of
      the initial radiolabel in the nasal cavity, consistent with clearance rates from
      the ciliated posterior surface. MFS deposited significant drug into the posterior
      nasal cavity. Both nasal cast validation and mucociliary clearance confirm the
      radiolabel deposition distribution method accurately represented corticosteroid
      nasal deposition. 

PMID- 25562557
TI  - Epidemiology of childhood peanut allergy.
AB  - Although peanut allergy is among the most common food allergies, no study has
      comprehensively described the epidemiology of the condition among the general
      pediatric population. Our objective was to better characterize peanut allergy
      prevalence, diagnosis trends, and reaction history among affected children
      identified from a representative sample of United States households with
      children. A randomized, cross sectional survey was administered to parents from
      June 2009 to February 2010. Data from 38,480 parents were collected and analyzed
      in regard to demographics, allergic symptoms associated with food ingestion, and
      methods of food allergy diagnosis. Adjusted models were estimated to examine
      association of these characteristics with odds of peanut allergy. Of the 3218
      children identified with food allergy, 754 (24.8%) were reported to have a peanut
      allergy. Peanut allergy was reported most often among 6- to 10-year-old children
      (25.5%), white children (47.7%), and children from households with an annual
      income of $50,000-$99,999 (41.7%). Although peanut allergy was diagnosed by a
      physician in 76% of cases, significantly more peanut allergy reactions were
      severe as compared with reactions to other foods (53.7% versus 41.0%, p < 0.001).
      Parents were significantly less likely to report tolerance to peanut as compared
      with the odds of tolerance reported for other foods (odds ratio 0.7, 95%
      confidence interval: 0.5-0.9). Childhood peanut allergy, which represents nearly
      a quarter of all food allergy, presents more severe reactions and is least likely
      to be outgrown. Although it is diagnosed by a physician in nearly three-fourths
      of all cases, socioeconomic disparities in regard to diagnosis persist. 

PMID- 25562558
TI  - Prevalence of exercise-induced cough in schoolchildren: a pilot study.
AB  - Association between exercise-induced bronchoconstriction (EIB) and physical
      activity has not been investigated in a natural school environment in a general
      pediatric population. Our objective was to determine the prevalence of exercise
      induced symptoms (cough, wheeze, chest tightness, dyspnea) and bronchospasm among
      schoolchildren during physical education (PE). A total of 557 schoolchildren from
      seven public schools were enrolled. Information regarding demographic
      characteristic, previously diagnosed asthma was obtained. All children attended
      45-minute PE lesson with similar exercise intensity. Pulmonary function tests
      were performed before and immediately after PE lesson. The diagnosis of EIB was
      defined as a forced expiratory volume in one second (FEV1) decrease from baseline
      of more than or equal to 10% with exercise. Cough and dyspnea after exercise were
      recorded. A total of 557 participants were included into the analysis. After PE
      lesson, 15.3% children suffered from cough, 0.9% reported dyspnea, and 10.1% had
      more than 10% fall in FEV1 from baseline. Among all participants, 5.9% had
      doctors' diagnosed asthma, 4.8% of them were treated with inhaled corticosteroids
      (ICS). Among children with cough, 21.5% had asthma and 17.6% experienced EIB.
      Among asthmatics, 48.6% suffered from cough and 18.2% had more than 10% fall in
      FEV1 from baseline after PE lesson. EIB was not affected by age, gender, body
      mass index, asthma diagnosis, and ICS use. Only cough (odds ratio: 2.21, 95%
      confidence interval: 1.16-4.23; p = 0.0161) was independently associated with
      EIB. This study showed a high prevalence of exercise-induced cough and/or 10%
      fall in FEV1 during activity lesson in a natural school environment in a large
      urban population of schoolchildren. Our results call for another studies
      addressing the impact of environment on exercise-induced symptoms. 

PMID- 25562559
TI  - Hereditary angioedema with a focus on the child.
AB  - Hereditary angioedema (HAE) is a rare disease that causes recurrent mucosal and
      cutaneous swelling. Skin swelling, abdominal pain, and airway swelling cause
      significant morbidity and potential mortality. Symptoms often appear early in
      life and accelerate around puberty. Despite this, there is a paucity of both data
      and treatment options for HAE in children in the United States. Our objective was
      to summarize the published data and perform a retrospective chart review on
      children with HAE to improve care of the child with the disease. A retrospective
      chart review study was performed after Institutional Review Board approval. A
      search of electronic medical records from 2001 to 2011 was performed for children
      aged 1 to 18 years with a confirmed diagnosis of HAE. Demographic patient
      information was obtained and analyzed. Twenty-five pediatric patients were
      identified with the diagnosis of HAE: 13 female and 12 male. The median age at
      diagnosis was seven years. The most common initial presenting symptom was
      swelling of the upper extremity, followed by abdominal pain, swelling of the face
      and/or lower extremity, and scrotal swelling. Three patients reported no previous
      symptoms and were diagnosed due to family history of HAE and positive laboratory
      testing. The majority of patients (84%) reported a family history of HAE.
      Accurate and timely diagnosis of HAE is imperative for children to prevent
      further morbidity and mortality associated with the disease. 

PMID- 25562560
TI  - Serum interleukin 17, interleukin 23, and interleukin 10 values in children with
      atopic eczema/dermatitis syndrome (AEDS): association with clinical severity and
      phenotype.
AB  - To date cytokines profile in AEDS is poorly described in children. We evaluated
      the interleukin (IL)-17, IL-23, and IL-10 levels in atopic eczema/dermatitis
      syndrome (AEDS) children and healthy controls, in atopic AEDS (aAEDS) and
      nonatopic (naAEDS) subtypes and their relationship with disease severity. A total
      of 181 children with aAEDS and 93 healthy children were evaluated. According to
      the skin-prick test (SPT) for allergens and serum total IgE, all patients were
      subdivided in two groups: 104 aAEDS and 77 naAEDS. In all patients, serum IL-17,
      IL-23, and IL-10 levels were detected. Serum IL-17 and IL-23 levels were
      significantly higher, and serum IL-10 levels were significantly lower in AEDS
      children than healthy group (p < 0.001). Moreover, serum IL-17 and IL-23 levels
      were significantly higher in aAEDS than in naAEDS subtypes (p < 0.001).
      Differently, serum IL-10 levels resulted similar in both subtypes. There was a
      correlation between Score Atopic Dermatitis (SCORAD) index and both IL-17 and IL
      23 and an inverse correlation between SCORAD index and IL-10 in aAEDS and naAEDS
      types. Serum IL-17 and IL-23 values were positively related to total IgE levels
      (p < 0.0001) in aAEDS. Further increase of IL-17 and IL-23 levels was detected in
      aAEDS subjects with atopic diseases such as asthma and rhinitis than children
      with only allergic sensitization. Our study confirms the role of IL-17, IL-23,
      and IL-10 and their relationship with the severity of AEDS. We firstly found a
      correlation between high IL-17/IL-23 axis levels and different phenotypes of AEDS
      in children, suggesting its role as marker of "atopic march" and disease
      severity. 

PMID- 25562561
TI  - A 15-year old girl with asthma and lower lobe bronchiectasis.
AB  - Wet cough, wheeze, and sputum in an adolescent with evidence for bronchiectasis
      is an uncommon presentation. The differential diagnosis includes cystic fibrosis
      (CF), immunodeficiency disorders, complement deficiency, allergic
      bronchopulmonary aspergillosis, alpha-1 antitrypsin disease, repeated aspiration
      pneumonia, foreign body, bronchial carcinoid, unresolved right middle lobe
      pneumonia, and primary ciliary dyskinesia (PCD). The likely diagnosis proceeds
      from the more to less common in patients with these symptoms. The location of
      disease on computed tomography scanning, nasal and bronchial exhaled nitric
      oxide, identification of ultrastructural defects on electron microscopy, and
      specific genetic mutation help separate CF and PCD. Although differentiating
      these conditions is vital, the chronic management of the bronchiectasis usually
      includes clearance mechanisms, bronchodilators, regular exercise, appropriate
      vaccinations, and judicious antibiotics for airway infections. 

PMID- 25562562
TI  - For the patient. The asthma-COPD overlap syndrome (ACOS): Is it asthma? Is it
      COPD? Or is it both?

PMID- 25562563
TI  - Methoxyflavones from Stachys glutinosa with binding affinity to opioid receptors:
      in silico, in vitro, and in vivo studies.
AB  - Fractionation of the bioactive dichloromethane extract from the aerial parts of
      Stachys glutinosa led to the isolation of four flavones, xanthomicrol (1),
      sideritoflavone (2), 8-methoxycirsilineol (3), and eupatilin (4), along with two
      neo-clerodane diterpenes, roseostachenone (8) and a new compound, 3alpha,4alpha
      epoxyroseostachenol (7). In order to study structure-activity relationships, two
      methoxyflavones [5-demethyltangeretin (5) and tangeretin (6)] were synthesized by
      the methoxylation of xanthomicrol. The isolated compounds (1-4, 7, and 8) as well
      as the xanthomicrol semisynthetic derivatives (5 and 6) were evaluated for their
      binding affinity to the MU and delta opioid receptors. Xanthomicrol was the most
      potent binder to both MU and delta receptors, with a Ki value of 0.83 and 3.6
      MUM, respectively. Xanthomicrol administered intraperitoneally in mice at a dose
      of 80 mg/kg significantly reduced morphine-induced antinociception in the tail
      flick test. Our results suggested that xanthomicrol is a MU opioid receptor
      antagonist. Docking experiments were carried out to acquire a deeper
      understanding about important structural aspects of binding of xanthomicrol. In
      summary, these data suggest that xanthomicrol is a valuable structure for further
      development into a potential MU opioid receptor antagonist. 

PMID- 25562564
TI  - Internal photoemission in molecular junctions: parameters for interfacial barrier
      determinations.
AB  - The photocurrent spectra for large-area molecular junctions are reported, where
      partially transparent copper top contacts permit illumination by UV-vis light.
      The effect of variation of the molecular structure and thickness are discussed.
      Internal photoemission (IPE), a process involving optical excitation of hot
      carriers in the contacts followed by transport across internal system barriers,
      is dominant when the molecular component does not absorb light. The IPE spectrum
      contains information regarding energy level alignment within a complete, working
      molecular junction, with the photocurrent sign indicating transport through
      either the occupied or unoccupied molecular orbitals. At photon energies where
      the molecular layer absorbs, a secondary phenomenon is operative in addition to
      IPE. In order to distinguish IPE from this secondary mechanism, we show the
      effect of the source intensity as well as the thickness of the molecular layer on
      the observed photocurrent. Our results clearly show that the IPE mechanism can be
      differentiated from the secondary mechanism by the effects of variation of
      experimental parameters. We conclude that IPE can provide valuable information
      regarding interfacial energetics in intact, working molecular junctions,
      including clear discrimination of charge transport mediated by electrons through
      unoccupied system orbitals from that mediated by hole transport through occupied
      system orbitals. 

PMID- 25562565
TI  - Combining targeted therapeutics in the era of precision medicine.

PMID- 25562566
TI  - Ghrelin-reactive immunoglobulins and anxiety, depression and stress-induced
      cortisol response in adolescents. The TRAILS study.
AB  - BACKGROUND: Ghrelin, a hunger hormone, has been implicated in the regulation of
      stress-response, anxiety and depression. Ghrelin-reactive immunoglobulins (Ig)
      were recently identified in healthy and obese humans showing abilities to
      increase ghrelin's stability and orexigenic effects. Here we studied if ghrelin
      reactive Ig are associated with anxiety and depression and with the stress
      induced cortisol response in a general population of adolescents. Furthermore, to
      test the possible infectious origin of ghrelin-reactive Ig, their levels were
      compared with serum IgG against common viruses. METHODS: We measured ghrelin
      reactive IgM, IgG and IgA in serum samples of 1199 adolescents from the Dutch
      TRAILS study and tested their associations with 1) anxiety and depression
      symptoms assessed with the Youth Self-Report, 2) stress-induced salivary cortisol
      levels and 3) IgG against human herpesvirus 1, 2, 4 and 6 and Influenza A and B
      viruses. RESULTS: Ghrelin-reactive IgM and IgG correlated positively with levels
      of antibodies against Influenza A virus. Ghrelin-reactive IgM correlated
      negatively with antibodies against Influenza B virus. Ghrelin-reactive IgM
      correlated positively with anxiety scores in girls and ghrelin-reactive IgG
      correlated with stress-induced cortisol secretion, but these associations were
      weak and not significant after correction for multiple testing. CONCLUSION: These
      data indicate that production of ghrelin-reactive autoantibodies could be
      influenced by viral infections. Serum levels of ghrelin-reactive autoantibodies
      probably do not play a role in regulating anxiety, depression and the stress
      response in adolescents from the general population.

PMID- 25562567
TI  - Fully probabilistic control for stochastic nonlinear control systems with input
      dependent noise.
AB  - Robust controllers for nonlinear stochastic systems with functional uncertainties
      can be consistently designed using probabilistic control methods. In this paper a
      generalised probabilistic controller design for the minimisation of the Kullback
      Leibler divergence between the actual joint probability density function (pdf) of
      the closed loop control system, and an ideal joint pdf is presented emphasising
      how the uncertainty can be systematically incorporated in the absence of reliable
      systems models. To achieve this objective all probabilistic models of the system
      are estimated from process data using mixture density networks (MDNs) where all
      the parameters of the estimated pdfs are taken to be state and control input
      dependent. Based on this dependency of the density parameters on the input
      values, explicit formulations to the construction of optimal generalised
      probabilistic controllers are obtained through the techniques of dynamic
      programming and adaptive critic methods. Using the proposed generalised
      probabilistic controller, the conditional joint pdfs can be made to follow the
      ideal ones. A simulation example is used to demonstrate the implementation of the
      algorithm and encouraging results are obtained. 

PMID- 25562568
TI  - Self-organizing maps based on limit cycle attractors.
AB  - Recent efforts to develop large-scale brain and neurocognitive architectures have
      paid relatively little attention to the use of self-organizing maps (SOMs). Part
      of the reason for this is that most conventional SOMs use a static encoding
      representation: each input pattern or sequence is effectively represented as a
      fixed point activation pattern in the map layer, something that is inconsistent
      with the rhythmic oscillatory activity observed in the brain. Here we develop and
      study an alternative encoding scheme that instead uses sparsely-coded limit
      cycles to represent external input patterns/sequences. We establish conditions
      under which learned limit cycle representations arise reliably and dominate the
      dynamics in a SOM. These limit cycles tend to be relatively unique for different
      inputs, robust to perturbations, and fairly insensitive to timing. In spite of
      the continually changing activity in the map layer when a limit cycle
      representation is used, map formation continues to occur reliably. In a two-SOM
      architecture where each SOM represents a different sensory modality, we also show
      that after learning, limit cycles in one SOM can correctly evoke corresponding
      limit cycles in the other, and thus there is the potential for multi-SOM systems
      using limit cycles to work effectively as hetero-associative memories. While the
      results presented here are only first steps, they establish the viability of SOM
      models based on limit cycle activity patterns, and suggest that such models merit
      further study. 

PMID- 25562569
TI  - Convergence and attractivity of memristor-based cellular neural networks with
      time delays.
AB  - This paper presents theoretical results on the convergence and attractivity of
      memristor-based cellular neural networks (MCNNs) with time delays. Based on a
      realistic memristor model, an MCNN is modeled using a differential inclusion. The
      essential boundedness of its global solutions is proven. The state of MCNNs is
      further proven to be convergent to a critical-point set located in saturated
      region of the activation function, when the initial state locates in a saturated
      region. It is shown that the state convergence time period is finite and can be
      quantitatively estimated using given parameters. Furthermore, the positive
      invariance and attractivity of state in non-saturated regions are also proven.
      The simulation results of several numerical examples are provided to substantiate
      the results. 

PMID- 25562570
TI  - 2H NMR pure-quadrupole spectra for paramagnetic solids.
AB  - We report a simple two-dimensional NMR method for obtaining (2)H NMR pure
      quadrupole spectra of paramagnetic solids. This method is based on a quadrupole
      echo sequence inserted with 180 degrees  pulses, where the pulse spacings are
      incremented asymmetrically so that the (2)H magnetization evolves only by the
      quadrupole interaction in the indirect dimension. It is shown that when the
      sequence is carried out with strong radio-frequency pulses, the spectrum
      projected to the indirect dimension can be simulated using the quadrupole-echo
      sequence without considering the effect of the paramagnetic shift. The method was
      also used to investigate molecular dynamics by measurement and simulation of the
      temperature dependence of the (2)H NMR spectra. 

PMID- 25562572
TI  - Dislocation-induced nanoparticle decoration on a GaN nanowire.
AB  - GaN nanowires with homoepitaxial decorated GaN nanoparticles on their surface
      along the radial direction have been synthesized by means of a chemical vapor
      deposition method. The growth of GaN nanowires is catalyzed by Au particles via
      the vapor-liquid-solid (VLS) mechanism. Screw dislocations are generated along
      the radial direction of the nanowires under slight Zn doping. In contrast to the
      metal-catalyst-assisted VLS growth, GaN nanoparticles are found to prefer to
      nucleate and grow at these dislocation sites. High-resolution transmission
      electron microscopy (HRTEM) analysis demonstrates that the GaN nanoparticles
      possess two types of epitaxial orientation with respect to the corresponding GaN
      nanowire: (I) [1210]np//[1210]nw, (0001)np//(0001)nw; (II) [1213]np//[1210]nw,
      (1010)np//(1010)nw. An increased Ga signal in the energy-dispersive spectroscopy
      (EDS) profile lines of the nanowires suggests GaN nanoparticle growth at the edge
      surface of the wires. All the crystallographic results confirm the importance of
      the dislocations with respect to the homoepitaxial growth of the GaN
      nanoparticles. Here, screw dislocations situated on the (0001) plane provide the
      self-step source to enable nucleation of the GaN nanoparticles. 

PMID- 25562571
TI  - NMR profiling of biomolecules at natural abundance using 2D 1H-15N and 1H-13C
      multiplicity-separated (MS) HSQC spectra.
AB  - 2D NMR (1)H-X (X=(15)N or (13)C) HSQC spectra contain cross-peaks for all XHn
      moieties. Multiplicity-edited(1)H-(13)C HSQC pulse sequences generate opposite
      signs between peaks of CH(2) and CH/CH(3) at a cost of lower signal-to-noise due
      to the (13)C T(2) relaxation during an additional 1/(1)JCH period. Such CHn
      editing experiments are useful in assignment of chemical shifts and have been
      successfully applied to small molecules and small proteins (e.g. ubiquitin)
      dissolved in deuterated solvents where, generally, peak overlap is minimal. By
      contrast, for larger biomolecules, peak overlap in 2D HSQC spectra is unavoidable
      and peaks with opposite phases cancel each other out in the edited spectra.
      However, there is an increasing need for using NMR to profile biomolecules at
      natural abundance dissolved in water (e.g., protein therapeutics) where NMR
      experiments beyond 2D are impractical. Therefore, the existing 2D multiplicity
      edited HSQC methods must be improved to acquire data on nuclei other than (13)C
      (i.e.(15)N), to resolve more peaks, to reduce T(2) losses and to accommodate
      water suppression approaches. To meet these needs, a multiplicity-separated(1)H-X
      HSQC (MS-HSQC) experiment was developed and tested on 500 and 700 MHz NMR
      spectrometers equipped with room temperature probes using RNase A (14 kDa) and
      retroviral capsid (26 kDa) proteins dissolved in 95% H(2)O/5% D(2)O. In this
      pulse sequence, the 1/(1)JXH editing-period is incorporated in to the semi
      constant time (semi-CT) X resonance chemical shift evolution period, which
      increases sensitivity, and importantly, the sum and the difference of the
      interleaved (1)J(XH)-active and the (1)J(XH)-inactive HSQC experiments yield two
      separate spectra for XH(2) and XH/XH(3). Furthermore we demonstrate improved
      water suppression using triple xyz-gradients instead of the more widely used z
      gradient only water-suppression approach.

PMID- 25562573
TI  - In vitro and in vivo characterization of antibacterial activity and
      biocompatibility: a study on silver-containing phosphonate monolayers on
      titanium.
AB  - Infections associated with implanted medical devices are a major cause of
      nosocomial infections, with serious medical and economic repercussions. A variety
      of silver-containing coatings have been proposed to decrease the risk of
      infection by hindering bacterial adhesion and biofilm formation. However, the
      therapeutic range of silver is relatively narrow and it is important to minimize
      the amount of silver in the coatings, in order to keep sufficient antibacterial
      activity without inducing cytotoxicity. In this study, the antibacterial
      efficiency and biocompatibility of nanocoatings with minimal silver loading
      (~0.65 nmol cm(-2)) was evaluated in vitro and in vivo. Titanium substrates were
      coated by grafting mercaptododecylphosphonic acid (MDPA) monolayers followed by
      post-reaction with AgNO3. The MDPA/AgNO3 nanocoatings significantly inhibited
      Escherichia coli and Staphylococcus epidermidis adhesion and biofilm formation in
      vitro, while allowing attachment and proliferation of MC3T3-E1 preosteoblasts.
      Moreover, osteogenic differentiation of MC3T3 cells and murine mesenchymal stem
      cells was not affected by the nanocoatings. Sterilization by ethylene oxide did
      not alter the antibacterial activity and biocompatibility of the nanocoatings.
      After subcutaneous implantation of the materials in mice, we demonstrated that
      MDPA/AgNO3 nanocoatings exhibit significant antibacterial activity and excellent
      biocompatibility, both in vitro and in vivo, after postoperative seeding with S.
      epidermidis. These results confirm the interest of coating strategies involving
      subnanomolar amounts of silver exposed at the extreme surface for preventing
      bacterial adhesion and biofilm formation on metallic or ceramic medical devices
      without compromising their biocompatibility.

PMID- 25562574
TI  - Intranasal immunization with fusion protein MrpH.FimH and MPL adjuvant confers
      protection against urinary tract infections caused by uropathogenic Escherichia
      coli and Proteus mirabilis.
AB  - Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC)
      and Proteus mirabilis are among the most common infections in the world.
      Currently there are no vaccines available to confer protection against UTI in
      humans. In this study, the immune responses and protection of FimH of UPEC with
      MrpH antigen of P. mirabilis in different vaccine formulations with and without
      MPL adjuvant were assessed. Mice intranasally immunized with the novel fusion
      protein MrpH.FimH induced a significant increase in IgG and IgA in serum, nasal
      wash, vaginal wash, and urine samples. Mice immunized with fusion MrpH.FimH also
      showed a significant boost in cellular immunity. Addition of MPL as the adjuvant
      enhanced FimH and MrpH specific humoral and cellular responses in both systemic
      and mucosal samples. Vaccination with MrpH.FimH alone or in combination with MPL
      showed the highest efficiency in clearing bladder and kidney infections in mice
      challenged with UPEC and P. mirabilis. These findings may indicate that the
      protection observed correlates with the systemic, mucosal and cellular immune
      responses induced by vaccination with these preparations. Our data suggest
      MrpH.FimH fusion protein with or without MPL as adjuvant could be potential
      vaccine candidates for elimination of UPEC and P. mirabilis. These data
      altogether are promising and these formulations are good candidates for
      elimination of UPEC and P. mirabilis.

PMID- 25562575
TI  - Appetite-regulatory hormone responses on the day following a prolonged bout of
      moderate-intensity exercise.
AB  - Exercise increases energy expenditure however acutely this does not cause
      compensatory changes in appetite or food intake. This unresponsiveness contrasts
      the rapid counter-regulatory changes seen after food restriction. The present
      investigation examined whether corrective changes in appetite-regulatory
      parameters occur after a time delay, namely, on the day after a single bout of
      exercise. Nine healthy males completed two, two-day trials (exercise & control)
      in a random order. On the exercise trial participants completed 90 min of
      moderate-intensity treadmill running on day one (10:30-12:00h). On day two
      appetite-regulatory hormones and subjective appetite perceptions were assessed
      frequently in response to two test meals provided at 08:00 and 12:00 h. Identical
      procedures occurred in the control trial except no exercise was performed on day
      one. Circulating levels of leptin were reduced on the day after exercise (AUC
      5841 +/- 3335 vs. 7266 +/- 3949 ng(-1).mL(-1).7h, P=0.012). Conversely, no
      compensatory changes were seen for circulating acylated ghrelin, total PYY,
      insulin or appetite perceptions. Unexpectedly, levels of acylated ghrelin were
      reduced on the exercise trial following the second test meal on day two (AUC 279
      +/- 136 vs. 326 +/- 136 pg(-1).mL(-1).3h, P=0.021). These findings indicate that
      short-term energy deficits induced by exercise initially prompt a compensatory
      response by chronic but not acute hormonal regulators of appetite and energy
      balance. Within this 24h time-frame however there is no conscious recognition of
      the perturbation to energy balance.

PMID- 25562576
TI  - Erectile dysfunction is associated with low total serum testosterone levels and
      impaired flow-mediated vasodilation in intermediate risk men according to the
      Framingham risk score.
AB  - BACKGROUND: The role erectile dysfunction (ED) coupled with low testosterone
      levels as early markers of atherosclerosis is not well understood. OBJECTIVES: To
      analyze the relationship between serum testosterone levels with both ED and
      brachial artery flow-mediated vasodilation (FMD), in a primary prevention sample
      of men. METHODS: We enrolled 802 asymptomatic, intermediate CV risk patients,
      according to the Framingham Risk Score, aged 40-80 years, who underwent the
      ultrasound examination of FMD, the evaluation of ED and the assessment of total
      serum testosterone levels. RESULTS: Testosterone levels correlated both with FMD
      (r = 0.85; p < 0.0001) and IIEF-5 score (rs = 0.65; p < 0.0001). Multivariable
      logistic regression analyses revealed that lower serum testosterone levels were
      strongly associated (p < 0.001) with severe (OR 0.78; 95% CI: 0.62-0.86), and
      moderate ED (OR 0.85; 95% CI: 0.72-0.97), while impaired FMD percentages were
      strongly associated (p < 0.001) with severe (OR 0.68; 95% CI: 0.59-0.79),
      moderate (OR 0.76; 95% CI: 0.63-0.83) and mild to moderate ED (OR 0.8; 95% CI:
      0.69-0.94). Mild ED resulted statistically associated with lower FMD (OR 0.94;
      95% CI: 0.82 - 1.07; p = 0.03) but not with serum testosterone levels. These
      relations were not substantially affected by adjustments for further potential
      confounders including smoking status, hypertension, diabetes mellitus and body
      mass index. CONCLUSIONS: lower total serum testosterone levels are associated
      with impaired FMD and ED in this sample of intermediate CV risk men according to
      the Framingham Risk Score.

PMID- 25562577
TI  - Parathyroid hormone and calcium are independently associated with subclinical
      vascular disease in a community-based cohort.
AB  - OBJECTIVE: Diseases with abnormal levels of parathyroid hormone (PTH) and
      calcium, such as primary and secondary hyperparathyroidism, are associated with
      an increased risk of cardiovascular morbidity and mortality. However, there is
      paucity on the association between calcium, PTH and abnormalities in the vascular
      system in the general population. METHODS: In the PIVUS study (Prospective
      Investigation of the Vasculature in Uppsala Seniors), a community based cohort of
      70-year old men and women (n = 1016), the associations between s-calcium, p-PTH
      and endothelial function, arterial stiffness and blood pressures were
      investigated, adjusting for cardiovascular risk factors and mineral metabolism.
      RESULTS: In multivariable linear regression models 1 SD increase in calcium was
      associated with 1.1 units decrease in the stroke volume/pulse pressure ratio and
      0.06 decrease in common carotid artery distensibility (p < 0.001) indicative of
      increased arterial stiffness. Further, calcium was associated with increasing
      calculated central pulse pressure with 1.3 mmHg elevation per 1 SD increase in
      calcium (p < 0.05). 1 SD increase in PTH was associated with 1.9 and 1.0 mmHg
      increase in intra-arterially measured brachial artery systolic and diastolic
      blood pressures, respectively (p < 0.01), as well as 1.6 and 0.9 mmHg increase in
      calculated central systolic and diastolic blood pressures (p < 0.05). PTH was not
      associated with arterial stiffness, endothelial function or pulse pressure.
      CONCLUSION: In a large community-based sample of elderly, calcium was
      independently associated with increased arterial stiffness, and PTH independently
      to intra-arterial peripheral and calculated central blood pressures. The findings
      indicate a possible link between the vasculature and mineral metabolism.

PMID- 25562580
TI  - The poly(I:C)-induced maternal immune activation model in preclinical
      neuropsychiatric drug discovery.
AB  - Increasing epidemiological and experimental evidence implicates gestational
      infections as one important factor involved in the pathogenesis of several
      neuropsychiatric disorders. Corresponding preclinical model systems based upon
      maternal immune activation (MIA) by treatment of the pregnant female have been
      developed. These MIA animal model systems have been successfully used in basic
      and translational research approaches, contributing to the investigation of the
      underlying pathophysiological mechanisms at the molecular, cellular and
      behavioral levels. The present article focuses on the application of a specific
      MIA rodent paradigm, based upon treatment of the gestating dam with the viral
      mimic polyinosinic-polycytidilic acid (Poly(I:C)), a synthetic analog of double
      stranded RNA (dsRNA) which activates the Toll-like receptor 3 (TLR3) pathway.
      Important advantages and constraints of this animal model will be discussed,
      specifically in light of gestational infection as one vulnerability factor
      contributing to the complex etiology of mood and psychotic disorders, which are
      likely the result of intricate multi-level gene*environment interactions.
      Improving our currently incomplete understanding of the molecular
      pathomechanistic principles underlying these disorders is a prerequisite for the
      development of alternative therapeutic approaches which are critically needed in
      light of the important drawbacks and limitations of currently available
      pharmacological treatment options regarding efficacy and side effects. The
      particular relevance of the Poly(I:C) MIA model for the discovery of novel drug
      targets for symptomatic and preventive therapeutic strategies in mood and
      psychotic disorders is highlighted in this review article. 

PMID- 25562578
TI  - The dynamics of QuantiFERON-TB gold in-tube conversion and reversion in a cohort
      of South African adolescents.
AB  - RATIONALE: Interferon-gamma release assays are used to diagnose tuberculosis
      infection. In developed countries, high rates of reversion following conversion
      have been described. OBJECTIVES: To assess QuantiFERON TB Gold In-Tube test (QFT)
      conversion and reversion dynamics in a tuberculosis-endemic setting. METHODS:
      Adolescents aged 12-18 years residing near Cape Town were recruited. Tuberculin
      skin tests (TSTs) and QFTs were performed at baseline and after 2 years of follow
      up. Half of the participants had TST and QFT performed at additional time points.
      Participants were observed for incident tuberculosis disease for up to 5 years.
      MEASUREMENTS AND MAIN RESULTS: Among 5,357 participants, 2,751 (51.4%) and 2,987
      (55.8%) had positive QFT and TST results, respectively, at baseline. Annualized
      QFT and TST conversion risks were 14.0 and 13.0%, respectively, and reversion
      risks were 5.1 and 4.1%, respectively. Concordance was excellent for conversions
      (kappa = 0.74), but poor for reversions (kappa = 0.12). Among recent QFT
      converters, the magnitude of the QFT value was strongly inversely associated with
      risk of reversion (P < 0.0001). When longitudinal QFT data were analyzed in a
      cross-sectional manner, the annual risk of infection was 7.3%, whereas inclusion
      of reversions in the analysis showed that the actual risk of infection was 14.0%.
      Incident tuberculosis was 8-fold higher among QFT reverters than in participants
      with all negative QFT results (1.47 vs. 0.18 cases/100 person-years, P = 0.011).
      CONCLUSIONS: In this tuberculosis-endemic setting, annual risk of infection was
      extremely high, whereas QFT and TST conversion concordance was higher and QFT
      reversion rates were lower than reported in low-burden settings.

PMID- 25562581
TI  - Relating methanogen community structure and anaerobic digester function.
AB  - Much remains unknown about the relationships between microbial community
      structure and anaerobic digester function. However, knowledge of links between
      community structure and function, such as specific methanogenic activity (SMA)
      and COD removal rate, are valuable to improve anaerobic bioprocesses. In this
      work, quantitative structure-activity relationships (QSARs) were developed using
      multiple linear regression (MLR) to predict SMA using methanogen community
      structure descriptors for 49 cultures. Community descriptors were DGGE demeaned
      standardized band intensities for amplicons of a methanogen functional gene
      (mcrA). First, predictive accuracy of MLR QSARs was assessed using cross
      validation with training (n = 30) and test sets (n = 19) for glucose and
      propionate SMA data. MLR equations correlating band intensities and SMA
      demonstrated good predictability for glucose (q(2) = 0.54) and propionate (q(2) =
      0.53). Subsequently, data from all 49 cultures were used to develop QSARs to
      predict SMA values. Higher intensities of two bands were correlated with higher
      SMA values; high abundance of methanogens associated with these two bands should
      be encouraged to attain high SMA values. QSARs are helpful tools to identify key
      microorganisms or to study and improve many bioprocesses. Development of new,
      more robust QSARs is encouraged for anaerobic digestion or other bioprocesses,
      including nitrification, nitritation, denitrification, anaerobic ammonium
      oxidation, and enhanced biological phosphorus removal.

PMID- 25562579
TI  - Prognostic subgroups for remission and response in the Coordinated Anxiety
      Learning and Management (CALM) trial.
AB  - OBJECTIVE: Most patients with anxiety disorders receive treatment in primary care
      settings. Limited moderator data are available to inform clinicians of likely
      prognostic outcomes for individual patients. We identify baseline characteristics
      associated with outcome in adults seeking treatment for anxiety disorders.
      METHOD: We conducted an exploratory moderator analysis from the Coordinated
      Anxiety Learning and Management (CALM) trial. In the CALM trial, 1,004 adults who
      met DSM-IV criteria for generalized anxiety disorder (GAD), panic disorder,
      social anxiety disorder, and/or posttraumatic stress disorder (PTSD) were
      randomized to usual care (UC) or a collaborative care intervention (ITV) of
      cognitive-behavioral therapy and/or pharmacotherapy between June 2006 and April
      2008. Logistic regression was used to examine baseline characteristics associated
      with remission and response overall and by treatment condition. Receiver
      operating curve (ROC) analyses identified subgroups associated with similar
      likelihood of response and remission of global anxiety symptoms. Remission was
      defined as score < 6 on the 12-item Brief Symptom Inventory (BSI-12) anxiety and
      somatization subscales. Response was defined as at least 50% reduction on BSI-12,
      or meeting remission criteria. RESULTS: Randomization to ITV over UC was often
      the strongest predictor of outcome. Several baseline patient characteristics were
      associated with poor treatment outcome including comorbid depression, increased
      severity of underlying anxiety disorder(s) (P < .001), low socioeconomic status
      (perceived [P < .001] and actual [P < .05]), and limited social support (P <
      .001). Patient characteristics associated with particular benefit from ITV were
      being female (P < .05), increased depression (P < .01)/GAD severity (P < .05),
      and low socioeconomic status (P < .05). ROC analysis demonstrated prognostic
      subgroups with large differences in response likelihood. CONCLUSIONS: Further
      research should focus on the effectiveness of implementing the ITV intervention
      of CALM in community treatment centers where patients typically are of low
      socioeconomic status and may particularly benefit from ITV. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00347269.

PMID- 25562582
TI  - Comprehensive study of the antidiabetic drug metformin and its transformation
      product guanylurea in Greek wastewaters.
AB  - Many pollutants such as pharmaceuticals and their transformation products (TPs)
      are not efficiently removed from wastewater treatment plants and enter into
      surface waters. The aim of this study was to investigate the occurrence and
      behavior of metformin, one of the most prescribed drugs worldwide, and its
      biological transformation product guanylurea, in eight wastewater treatment
      plants (WWTPs) of Greece. All WWTPs were equipped with conventional activated
      sludge treatment and the samples were taken from the influents and the effluents,
      over the four seasons of one year. The analytical method developed based on SPE
      followed by LC-UV/Vis-ESI/MS analysis, while positive findings were confirmed
      also by means of LTQ Orbitrap mass spectrometer. High polarity of both compounds
      led to the extraction with Oasis HLB and the use of the anionic surfactant SDS.
      The results showed that metformin dominated in the influents (bql-1167 ng/L),
      while guanylurea in the effluents (bql-627 ng/L) of the wastewater treatment
      plants, with Metformin/Guanylurea ratio ranging between 0.88 and 81.3 in the
      influents and between 0.005 and 0.78 in the effluents. Lack of a clear seasonal
      tendency in the occurrence and removal or formation was observed. Finally, an
      ecotoxicological risk assessment of metformin in effluent wastewaters took place
      by calculating the ratio between the environmental concentrations (MEC) and the
      predicted no effect concentrations (PNEC). Despite the fact that metformin
      presented low risk in all cases, an environmental concern is suspected for
      guanylurea since it is continuously released into the aquatic environment. 

PMID- 25562584
TI  - Effect of tip mass on frequency response and sensitivity of AFM cantilever in
      liquid.
AB  - The effect of tip mass on the frequency response and sensitivity of atomic force
      microscope (AFM) cantilever in the liquid environment is investigated. For this
      purpose, using Euler-Bernoulli beam theory and considering tip mass and
      hydrodynamic functions in a liquid environment, an expression for the resonance
      frequencies of AFM cantilever in liquid is derived. Then, based on this
      expression, the effect of the surface contact stiffness on the flexural mode of a
      rectangular AFM cantilever in fluid is investigated and compared with the case
      where the AFM cantilever operates in the air. The results show that in contrast
      with an air environment, the tip mass has no significant impact on the resonance
      frequency and sensitivity of the AFM cantilever in the liquid. Hence, analysis of
      AFM behaviour in liquid environment by neglecting the tip mass is logical. 

PMID- 25562583
TI  - Enhanced protein adsorption and facilitated refolding of like-charged protein
      with highly charged silica nanoparticles fabricated by sequential double
      modifications.
AB  - Silica nanoparticles (SNPs) were sequentially modified with poly(ethylenimine)
      (PEI) and 2-diethylaminoethyl chloride (DEAE) to prepare a series of positively
      charged SNPs-PEI and SNPs-PEI-DEAE. The sequential double-modification strategy
      produced a charge density as high as 1740 MUmol/g (4524 MUmol/mL), which offered
      a very high adsorption capacity for bovine serum albumin (314 mg/g). Most
      importantly, the highly charged SNPs-PEI and SNPs-PEI-DEAE could efficiently
      facilitate the refolding of like-charged protein at extremely low utilization.
      For instance, in the refolding of 1 mg/mL lysozyme, the refolding yield reached
      75% with only 3.3 MUL/mL SNPs-PEI-DEAE. The bead consumption was reduced by
      nearly 96% as compared to that of the charged microspheres used previously to
      reach a similar yield. The results proved that the polyelectrolyte-modified SNPs
      were promising for applications in facilitating like-charged protein refolding,
      and the research opened up a new way for biotechnology applications of highly
      charged nanoparticles. 

PMID- 25562586
TI  - Retrospective analysis for the identification of 4-aminocarminic acid photo
      degradation products in beverages.
AB  - This article deals with the identification of the photo-degradation products of 4
      aminocarminic acid potentially present in commercial beverages. Sixteen beverages
      of different composition but all containing the E120 dye were previously analysed
      by ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole
      time of flight mass spectrometry to identify the common degradation products of
      the E120 dye. Since it is plausible to find unauthorised 4-aminocarminic acid in
      beverages which report generic E120 dye on the label, retrospective analysis was
      employed here not only to search for the possible presence of 4-aminocarminic
      acid but also to investigate the potential formation of photo-degradation
      products derived from this compound. For this purpose, a statistical approach
      based on Student's t-test was used to compare the degraded beverages containing 4
      aminocarminic acid with all the others. Five degradation products were identified
      and their structures were elucidated on the basis of the high-accuracy and high
      resolution of mass and mass/mass spectra. The toxicity of the degradation
      products was evaluated through the Ames Salmonella/microsome mutagenicity assay.
      No evidence of mutagenicity was obtained for the beverages subjected or not to
      irradiation, whereas a toxic effect of the 4-aminocarminic acid standard solution
      already at 100.0 ug l(-1) was found. This leads, once again, to the conclusion
      that the toxicity study must be carried out on the beverages in order to take
      into account of all the possible masking/protection interactions among the
      ingredients.

PMID- 25562585
TI  - Biological Matrix Effects in Quantitative Tandem Mass Spectrometry-Based
      Analytical Methods: Advancing Biomonitoring.
AB  - The ability to quantify levels of target analytes in biological samples
      accurately and precisely in biomonitoring involves the use of highly sensitive
      and selective instrumentation such as tandem mass spectrometers and a thorough
      understanding of highly variable matrix effects. Typically, matrix effects are
      caused by co-eluting matrix components that alter the ionization of target
      analytes as well as the chromatographic response of target analytes, leading to
      reduced or increased sensitivity of the analysis. Thus, before the desired
      accuracy and precision standards of laboratory data are achieved, these effects
      must be characterized and controlled. Here we present our review and observations
      of matrix effects encountered during the validation and implementation of tandem
      mass spectrometry-based analytical methods. We also provide systematic,
      comprehensive laboratory strategies needed to control challenges posed by matrix
      effects in order to ensure delivery of the most accurate data for biomonitoring
      studies assessing exposure to environmental toxicants. 

PMID- 25562587
TI  - Reply to: "Correspondence to: Predictors of in-hospital mortality amongst
      octogenarians undergoing emergency general surgery: A retrospective cohort
      study".

PMID- 25562588
TI  - General last-step labeling of biomolecule-based substrates by [12C], [13C], and
      [11C] carbon monoxide.
AB  - Alkaloid-, steroid-, biotin-, carbohydrate-, nucleoside-, and peptide-based
      bioconjugates are easily labeled with CO by a last-step palladium-catalyzed
      carbonylation. The choice of the [(12)C], [(13)C], or [(11)C] isotope opens the
      way to a new class of potential tracers or ligands easily available for various
      applications. 

PMID- 25562589
TI  - Increased mRNA expression of selected pro-inflammatory factors in inflamed bovine
      endometrium in vivo as well as in endometrial epithelial cells exposed to
      Bacillus pumilus in vitro.
AB  - Endometrial epithelium plays a crucial role in the first immune response to
      invading bacteria by producing cytokines and chemokines. The aim of this study
      was to investigate the first inflammatory response of the endometrium in vivo and
      in vitro. Gene expression of several pro-inflammatory factors and Toll-like
      receptors (TLR2, -4, -6) was determined in endometrial cytobrush samples obtained
      from healthy cows and cows with clinical or subclinical endometritis. Endometrial
      epithelial cells were co-cultured with an isolated autochthonous uterine
      bacterial strain Bacillus pumilus. Total RNA was extracted from in vivo and in
      vitro samples and subjected to real-time reverse transcription polymerase chain
      reaction. CXC ligands (CXCL) 1/2 and CXC chemokine receptor (CXCR) 2 mRNA
      expression was higher in cows with subclinical endometritis and CXCL3 mRNA
      expression was higher in cows with clinical endometritis compared with healthy
      cows. B. pumilus induced cell death of epithelial cells within 24h of co
      culturing. The presence of B. pumilus resulted in significantly higher mRNA
      expression of interleukin 1alpha (IL1A), IL6, IL8, CXCL1-3 and prostaglandin
      endoperoxide synthase 2 in co-cultured cells compared with untreated controls.
      The maximum increase was mainly detected after 2h. These results support the
      hypothesis that bacterial infection of endometrial cells might induce prompt
      synthesis of pro-inflammatory cytokines resulting in a local inflammatory
      reaction.

PMID- 25562590
TI  - A role for AT1 receptor-associated proteins in blood pressure regulation.
AB  - The renin angiotensin-system is one of the most important humoral regulators of
      blood pressure. The recently discovered angiotensin receptor-associated proteins
      serve as local modulators of the renin angiotensin-system. These proteins
      interact with the AT1 receptor in a tissue-specific manner and regulate the
      sensitivity of the target cell for angiotensin II. The predominant effect of the
      AT1 receptor-associated proteins on angiotensin II-induced signaling is the
      modulation of the surface expression of the AT1 receptor. This review provides an
      overview of our current knowledge with respect to the relevance of AT1 receptor
      associated proteins for blood pressure regulation. Two aspects of blood pressure
      regulation will be discussed in detail: angiotensin II-dependent volume
      homoeostasis and vascular resistance. 

PMID- 25562591
TI  - Determinants of patient-rated and clinician-rated illness severity in
      schizophrenia.
AB  - OBJECTIVE: The contribution of specific symptoms on ratings of global illness
      severity in patients with schizophrenia is not well understood. The present study
      examined the clinical determinants of clinician and patient ratings of overall
      illness severity. METHOD: This study included 1,010 patients with a DSM-IV
      diagnosis of schizophrenia who participated in the baseline visit of the Clinical
      Antipsychotic Trials of Intervention Effectiveness (CATIE) study conducted
      between January 2001 and December 2004 and who had available symptom severity,
      side effect burden, cognition, and community functioning data. Both clinicians
      and patients completed the 7-point Clinical Global Impressions-Severity of
      Illness scale (CGI-S), the primary measure of interest in the present study.
      Symptoms were rated using the Positive and Negative Syndrome Scale and the
      Calgary Depression Scale for Schizophrenia, and functional status with the
      Quality of Life Scale. Neurocognition, insight, and medication-related side
      effects were also evaluated. RESULTS: Clinicians rated illness severity
      significantly higher than patients (P < .001). There was moderate overlap between
      CGI-S ratings made by clinicians and patients, with almost one third of patients
      showing substantial (ie, greater than 1 point) discrepancies with clinician
      ratings. Clinician-rated CGI-S scores were most strongly associated with positive
      symptoms, with additional independent contributions made by negative,
      disorganized, and depressive symptoms, as well as functional outcome (all P
      values < .01). Patient-rated CGI-S scores, on the other hand, were most closely
      related to depressive symptoms, with additional independent contributions made by
      positive and anxiety symptoms, clinical insight, and neurocognition (all P values
      < .01). Depressive symptoms were the strongest predictor of patient-rated CGI-S
      scores even in patients with good clinical insight (P < .001). CONCLUSIONS:
      Patient and clinician views of overall illness severity are not necessarily
      interchangeable and differ in their clinical correlates. Taking these differences
      into account may enhance patient engagement in care and improve outcomes. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT00014001.

PMID- 25562592
TI  - The relations among relatedness needs, subjective well-being, and depression of
      Korean elderly.
AB  - The first part of the study examined what the relatedness needs Korean elderly
      have in close relationships (spouse, children, friends) are. The most salient
      needs were "love and care" for spouse and "contact and often meeting" for
      children and friends. The second part of the study assessed the relations among
      the difference between expectation and satisfaction of relatedness needs,
      subjective well-being, and depression of Korean elderly. Regression analyses
      showed that the difference between expectation and satisfaction of relatedness
      needs for spouse and children significantly predicted subjective well-being and
      depression. Finally, gender differences are discussed in terms of the patriarchal
      culture of Korean society. 

PMID- 25562593
TI  - Low-surface-area hard carbon anode for na-ion batteries via graphene oxide as a
      dehydration agent.
AB  - Na-ion batteries are emerging as one of the most promising energy storage
      technologies, particularly for grid-level applications. Among anode candidate
      materials, hard carbon is very attractive due to its high capacity and low cost.
      However, hard carbon anodes often suffer a low first-cycle Coulombic efficiency
      and fast capacity fading. In this study, we discover that doping graphene oxide
      into sucrose, the precursor for hard carbon, can effectively reduce the specific
      surface area of hard carbon to as low as 5.4 m(2)/g. We further reveal that such
      doping can effectively prevent foaming during caramelization of sucrose and
      extend the pyrolysis burnoff of sucrose caramel over a wider temperature range.
      The obtained low-surface-area hard carbon greatly improves the first-cycle
      Coulombic efficiency from 74% to 83% and delivers a very stable cyclic life with
      95% of capacity retention after 200 cycles. 

PMID- 25562594
TI  - Vancomycin-resistance phenotypes, vancomycin-resistance genes, and resistance to
      antibiotics of enterococci isolated from food of animal origin.
AB  - In the present study, 500 raw beef, pork, and chicken meat samples and 100 pooled
      egg samples were analyzed for the presence of vancomycin-resistant enterococci,
      vancomycin-resistance phenotypes, and resistance genes. Of 141 isolates of
      enterococci, 88 strains of Enterococcus faecium and 53 strains of E. faecalis
      were identified. The most prevalent species was E. faecium. Resistance to
      ampicillin (n = 93, 66%), ciprofloxacin (n = 74, 52.5%), erythromycin (n = 73,
      51.8%), penicillin (n = 59, 41.8%) and tetracycline (n = 52, 36.9%) was observed,
      while 53.2% (n = 75) of the isolates were multiresistant and 15.6% (n = 22) were
      susceptible to all antibiotics. Resistance to vancomycin was exhibited in 34.1%
      (n = 30) of the E. faecium isolates (n = 88) and 1.9% (n = 1) of the E. faecalis
      isolates (n = 53) using the disc-diffusion test and the E-test. All isolates were
      tested for vanA and vanB using real-time polymerase chain reaction (PCR) and
      multiplex PCR, and for vanC, vanD, vanE, vanG genes using multiplex PCR only.
      Among E. faecalis isolates, no resistance genes were identified. Among the E.
      faecium isolates, 28 carried the vanA gene when tested by multiplex PCR and 29
      when tested with real-time PCR. No isolate carrying the vanC, vanD, vanE, or vanG
      genes was identified. Melting-curve analysis of the positive real-time PCR E.
      faecium isolates showed that 22 isolates carried the vanA gene only, 2 isolates
      the vanB2,3 genes only, and seven isolates carried both the vanA and vanB2,3
      genes. Enterococci should be considered a significant zoonotic pathogen and a
      possible reservoir of genes encoding resistance potentially transferred to other
      bacterial species.

PMID- 25562595
TI  - Developing drugs for children and the adjustment of medication-is it a new
      challenge or an adaptation of past ideas?
AB  - Nowadays the adjustment of medication for each patient is at the center of health
      strategy. Children can be considered as specific targets with their own
      specificities. In the oral route field some examples of drugs especially adapted
      to children can be found. Design is introduced in drug formulation to offer a
      better choice of products and now, children can be considered as partners in
      their own treatment. Enhanced comprehension of children's requirements can also
      lead to creation of drugs that improve compliance. 

PMID- 25562596
TI  - Renal cell carcinoma with t(6:11) (p21;q12). A case report highlighting
      distinctive immunohistologic features of this rare tumor.
AB  - INTRODUCTION: Renal cell carcinoma (RCC) with t(6:11) (p21;q12) are extremely
      rare, fewer than 30 cases have been reported in literature. These tumors are
      characterized by specific chromosomal translocation involving TFEB, as against
      the more commonly known TFE3 (Xp11.2) translocation associated RCCs. The
      distinctive immnohistologic features are helpful in enabling a diagnosis of this
      rare tumor, otherwise diagnosed by fluorescence in situ hybridization assay,
      specific for detecting TFEB gene rearrangement. PRESENTATION OF CASE: Herein, we
      report a case of this rare tumor in a 11 years old boy, with the objective of
      highlighting distinctive light microscopic and immuno-phenotypic features of this
      rare sub-type of translocation associated renal cell carcinoma, otherwise
      diagnosed by fluorescence in situ hybridization technique. Morphologically tumor
      showed distinctive biphasic population of cells, large epitheloid cells with
      voluminous eosinophillic cytoplasm and smaller cells with much lesser amount of
      cytoplasm and small rounded nuclei. The smaller cells at places clustered around
      hyaline pink material forming "pseudorosettes". population. Immunohistochemically
      both types of tumor cells showed negativity for pan CK (cytokeratin), EMA
      (epitheleal membrane antigen) and TFE3 (transcription factor E3). HMB 45 (human
      melanoma black 45) and Melan- A /MART 1 (melanoma antigen recognized by T cells)
      were moderate to strongly expressed. DISCUSSION: On review of literature, most
      RCCs with t(6;11) translocation have been reported to be negative for pan
      cytokeratins and EMA. Published literature also shows that the most distinctive
      immunohistochemical feature of t(6;11) translocation RCC is nuclear staining for
      TFEB protein. Immunostains for TFE3 have always been negative in the reported
      cases. It is noteworthy that immunoreactivity for melanocytic markers HMB45 and
      Melan A and immunonegativity for epithelial markers pan CK and EMA may lead to
      misdiagnosis of angiomyolipoma to the unwary. CONCLUSION: Knowledge of
      distinctive morphological and immuno-histochemical features of this tumor can
      help in establishing a diagnosis of this rare subset of translocation associated
      RCC on routine hematoxylin and eosin (H and E) staining and immunophenotyping.

PMID- 25562598
TI  - Hydatidosis of the liver and posterior mediastinum.
AB  - INTRODUCTION: Cystic echinococcus (CE) is an endemic zoonosis secondary to
      infection by the larval form of the cestode Echinococcus granulosus. An
      intermediate host, humans enter the organism's life cycle by exposure to infected
      canid feces. The liver is the most common location of CE while mediastinal
      hydatid cysts are rarely reported. PRESENTATION OF CASE: We report a case of
      synchronous CE of the liver and posterior mediastinum treated sequentially using
      chemotherapy, percutaneous aspiration with injection of a scolicidal agent and re
      aspiration (PAIR) and then staged minimally-invasive surgeries. DISCUSSION:
      Synchronous CE involving the liver and posterior mediastinum is rare. The
      treatment of hydatid liver and mediastinal disease is multimodal including
      chemotherapy, percutaneous and laparoscopic or open surgical interventions. One
      option for controlled puncture of hepatic and mediastinal CE includes PAIR
      followed by surgery. CONCLUSION: The sequential use of chemotherapy and PAIR
      followed by surgery provides another treatment strategy for management of CE. We
      believe this strategy may be used safely in locations without endemic CE,
      including most regions of the United States.

PMID- 25562597
TI  - Chronic wrist pain in a goalkeeper; bilateral scaphoid stress fracture: A case
      report.
AB  - INTRODUCTION: Bilateral scaphoid stress fractures are uncommon, and rarely
      presented with chronic wrist pain. Most fractures of the scaphoid heal with
      immobilization. Presentation of case The case presented here is of a bilateral
      stress fractures of the carpal scaphoid in a 19-year-old male.The patient had
      been playing as a goalkeeper and presented with a 4-year history of chronic pain
      in both wrists. We had a successful result in the treatment of these stress
      fractures with long- arm thumb plaster cast.Discussion Most fractures of the
      scaphoid in the immature skeleton heal with immobilization. Approximately 88-95%
      of acute scaphoid fractures are said to heal with conservative treatment using
      cast immobilisation. Non-surgical treatment is successful for scaphoid fractures
      in children and for those fractures which are non-displaced, stable, and where
      there is no damage to other bones or ligaments. In stable fractures, union is
      achieved within 8-12 weeks.Conclusion Bilateral stress fractures of the scaphoid
      can be considered for the wrist pain, especially for the patients that had
      repetitive minor wrist trauma, and in spite of developments in surgical
      techniques and materials used, treatment by plaster casting should still be
      considered initially for non-displaced, stable scaphoid stress fractures.

PMID- 25562600
TI  - Information-theoretic implications of quantum causal structures.
AB  - It is a relatively new insight of classical statistics that empirical data can
      contain information about causation rather than mere correlation. First
      algorithms have been proposed that are capable of testing whether a presumed
      causal relationship is compatible with an observed distribution. However, no
      systematic method is known for treating such problems in a way that generalizes
      to quantum systems. Here, we describe a general algorithm for computing
      information-theoretic constraints on the correlations that can arise from a given
      causal structure, where we allow for quantum systems as well as classical random
      variables. The general technique is applied to two relevant cases: first, we show
      that the principle of information causality appears naturally in our framework
      and go on to generalize and strengthen it. Second, we derive bounds on the
      correlations that can occur in a networked architecture, where a set of few-body
      quantum systems is distributed among some parties. 

PMID- 25562601
TI  - Professor Bengt Saltin (1935-2014): a personal tribute.

PMID- 25562599
TI  - Crucial role of IL1beta and C3a in the in vitro-response of multipotent
      mesenchymal stromal cells to inflammatory mediators of polytrauma.
AB  - Multipotent mesenchymal stromal cells (MSC) exert immune-modulatory effects and
      support tissue regeneration in various local trauma models. In case of a
      polytrauma, high amounts of danger-associated molecular patterns are released,
      leading to a systemic increase of inflammatory mediators. The influence of such a
      complex inflammatory microenvironment on human MSC is mainly unknown so far.
      Therefore, we investigated the effects of a defined serum-free polytrauma
      "cocktail" containing IL beta, IL6, IL8 and the anaphylatoxins C3a and C5a, in
      concentrations corresponding to those measured in the blood of polytrauma
      patients, on human MSC in vitro. The polytrauma cocktail induced directed
      migration of MSC with C3a representing its major soluble chemoattractive agent.
      Furthermore, the polytrauma cocktail and IL1beta upregulated the expression of
      MMP1 indicating a potential role of IL1beta to enhance MSC migration in the
      tissue context. COX2, PTGES and TSG6 were also found to be upregulated upon
      stimulation with the polytrauma cocktail or IL1beta, but not through other single
      factors of the polytrauma cocktail in pathophysiologically relevant
      concentrations. An RNA expression array of 84 inflammation-related genes revealed
      that both the polytrauma cocktail and IL1beta induced C3, CSF1, TLR3 and various
      chemokines without major qualitative or quantitative differences. These results
      indicate that IL1beta is a crucial mediator of the polytrauma cocktail in terms
      of immune-modulation and MMP1 expression. Thus, upon encountering the primary
      sterile, inflammatory milieu of a polytrauma, endogenous or systemically
      transfused MSC might be able to migrate to sites of injury, secrete TSG6 and PGE2
      and to influence macrophage biology as observed in local trauma models.

PMID- 25562602
TI  - Computational framework explains how animals select actions with rewarding
      outcomes.
AB  - A new model of how the brain learns beneficial behavior from rewarding outcomes
      emphasizes the importance of the striatum, replicates experimental data, and
      raises new questions about neurological disorders. Read the Research Article.

PMID- 25562603
TI  - Comparison of a novel test for placental alpha microglobulin-1 with fetal
      fibronectin and cervical length measurement for the prediction of imminent
      spontaneous preterm delivery in patients with threatened preterm labor.
AB  - OBJECTIVE: PartoSure is a bedside test for the prediction of time-to-spontaneous
      preterm delivery by the detection of placental alpha microglobulin-1 (PAMG-1).
      The objectives of this study were to further determine the test's efficacy in
      predicting delivery within 7 or 14 days from testing, and to compare it with
      fetal fibronectin (fFN) and cervical length (CL) measurement by transvaginal
      ultrasound. STUDY DESIGN: The study population consisted of 203 consecutively
      recruited women with singleton pregnancies between 200/7 and 366/7 weeks of
      gestation with symptoms of preterm labor, clinically intact membranes, and
      cervical dilatation of <=3 cm. PartoSure and CL were performed on all patients
      and the test-to-spontaneous-delivery interval was calculated. In a sub-segment of
      patients, the QuikCheck fFN test was used. RESULTS: The sensitivities for
      PartoSure (n=203), fFN (n=66), and CL (n=203) for predicting imminent spontaneous
      preterm delivery within 7 days were 80%, 50%, and 57%, respectively. The
      specificities were 95%, 72%, and 73% for PartoSure, fFN and CL, respectively. The
      NPVs were 96%, 87%, and 89% for PartoSure, fFN and CL, respectively. The PPVs
      were 76%, 29%, and 30% for PartoSure, fFN and CL, respectively. CONCLUSION: PAMG
      1 detection by PartoSure is the single best predictor of imminent spontaneous
      delivery within 7 days compared to fFN and CL. In settings where CL is used as an
      initial screen, PartoSure has the greatest clinical utility in patients with CL
      between 15 and 35 mm. In situations where CL is not an initial screen, PartoSure
      is the most accurate test compared to fFN and CL.

PMID- 25562604
TI  - C-terminal truncation of a Tat passenger protein affects its membrane
      translocation by interfering with receptor binding.
AB  - During thylakoid transport of the chimeric model twin-arginine translocation
      (Tat) substrate 16/23, two consecutive translocation intermediates with different
      membrane topology are observed. The early translocation intermediate Ti-1 is
      bound to the membrane such that almost half of the protein is protected against
      proteolysis and it was concluded that not only the signal peptide but also part
      of the passenger protein participates in membrane binding. However, topology
      studies using a membrane-impermeable thiol-reactive reagent show that most of the
      passenger remains accessible from the stromal side in Ti-1 conformation.
      Establishment of such Ti-1 topology at the membrane apparently requires the fully
      folded passenger protein, as it was not observed with 16/23 truncation
      derivatives lacking the C-terminal 20, 40, 60, or 88 residues. Thylakoid
      transport of these mutants, which depends on a fully functional Tat machinery, is
      progressively reduced with increasing size of the truncated passenger
      polypeptide. The same holds true also for the interaction with the thylakoidal
      TatBC complexes, suggesting that in this case receptor binding, which is
      apparently impaired by extended unfolded or malfolded passenger polypeptides, is
      the rate-limiting step of Tat-dependent membrane transport. 

PMID- 25562605
TI  - Relationship between antiphosphatidylserine/prothrombin and conventional
      antiphospholipid antibodies in primary antiphospholipid syndrome.
AB  - BACKGROUND: Antiphosphatidylserine/prothrombin complex (aPS/PT) antibodies are
      emerging as an important marker for antiphospholipid syndrome (APS). We aimed to
      compare their performance with that of conventional antiphospholipid antibodies
      (aPL) such as lupus anticoagulant (LA), anticardiolipin (aCL), and anti-beta2
      glycoprotein I (anti-beta2GPI) in APS and to assess their frequency in APS
      negative (APS-ne) patients. METHODS: We considered 160 APS patients and 128 APS
      ne patients with clinical criteria for APS but tested negative for conventional
      aPL. Immunoglobulin (Ig)G/IgM aPS/PT, IgG/IgM aCL, and IgG/IgM anti-beta2GPI were
      detected using ELISA assay and LA with a series of coagulation tests. RESULTS:
      IgG aPS/PT were significantly associated with IgG aCL, IgG anti-beta2GPI, and LA
      (p<0.0001 for all). IgM aPS/PT were significantly associated only with LA
      (p<0.0001) instead. There was a significant correlation between IgG aPS/PT and
      both IgG aCL and IgG anti-beta2GPI levels (rho=0.42 and rho=0.40, respectively).
      Both IgG aPS/PT and IgM aPS/PT positivity significantly correlated with LA
      (rho=0.44 and rho=0.5, respectively). IgG and IgM aPS/PT were significantly more
      frequent in triple than in double and in single positivity (p<0.0001). According
      to multivariate analysis, IgG and/or IgM aPS/PT were independent risk factors for
      LA. APS/PT antibodies were found in 9.4% of the APS-ne patients vs. 2% of healthy
      control (p=0.043); those antibodies were significantly more frequent in the
      thrombosis with respect to the pregnancy morbidity subset (p=0.01). CONCLUSIONS:
      Our data attribute a clinical relevance to both IgG and IgM aPS/PT antibodies. In
      particular, the significant prevalence of aPS/PT in APS-ne patients suggests
      including them as additional laboratory criterion for APS.

PMID- 25562606
TI  - TRPM2-mediated intracellular Zn2+ release triggers pancreatic beta-cell death.
AB  - Reactive oxygen species (ROS) can cause pancreatic beta-cell death by activating
      transient receptor potential (melastatin) 2 (TRPM2) channels. Cell death has been
      attributed to the ability of these channels to raise cytosolic Ca2+. Recent
      studies however revealed that TRPM2 channels can also conduct Zn2+, but the
      physiological relevance of this property is enigmatic. Given that Zn2+ is
      cytotoxic, we asked whether TRPM2 channels can permeate sufficient Zn2+ to affect
      cell viability. To address this, we used the insulin secreting (INS1) beta-cell
      line, human embryonic kidney (HEK)-293 cells transfected with TRPM2 and
      pancreatic islets. H2O2 activation of TRPM2 channels increases the cytosolic
      levels of both Ca2+ and Zn2+ and causes apoptotic cell death. Interestingly,
      chelation of Zn2+ alone was sufficient to prevent beta-cell death. The source of
      the cytotoxic Zn2+ is intracellular, found largely sequestered in lysosomes.
      Lysosomes express TRPM2 channels, providing a potential route for Zn2+ release.
      Zn2+ release is potentiated by extracellular Ca2+ entry, indicating that Ca2+
      induced Zn2+ release leads to apoptosis. Knockout of TRPM2 channels protects mice
      from beta-cell death and hyperglycaemia induced by multiple low-dose
      streptozotocin (STZ; MLDS) administration. These results argue that TRPM2
      mediated, Ca2+-potentiated Zn2+ release underlies ROS-induced beta-cell death and
      Zn2+, rather than Ca2+, plays a primary role in apoptosis. 

PMID- 25562607
TI  - Quercetin and its metabolites inhibit the membrane NADPH oxidase activity in
      vascular smooth muscle cells from normotensive and spontaneously hypertensive
      rats.
AB  - Quercetin, the most abundant dietary flavonol, exerts antioxidant effects
      reducing vascular superoxide (O2(-)) and improving endothelial function in animal
      models of cardiovascular disease. Herein we evaluated the effects of quercetin,
      and its plasma metabolites, on the nicotinamide adenine dinucleotide phosphate
      (NADPH)-oxidase activity, the main source of O2(-) in the vessel wall, in
      vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR)
      and normotensive Wistar Kyoto rats (WKY). Quercetin and its metabolites
      isorhamnetin and kaempferol inhibited the NADPH-stimulated lucigenin
      chemiluminescence signal in VSMCs from both strains. The inhibitory effect of
      quercetin-3-glucuronide increased after prolonged incubation and was inhibited in
      the presence of the beta-glucuronidase inhibitor saccharolactone. These effects
      were unrelated to their O2(-) scavenging properties, since they induced only a
      small inhibition of the rate of pyrogallol autoxidation at high concentrations.
      All bioflavonoids tested acted as non-competitive inhibitors with respect to
      NADPH. In conclusion, quercetin and its metabolites inhibit the NADPH oxidase
      activity in VSMCs reducing O2(-) generation more efficiently than their effect as
      O2(-) scavengers. The effect of quercetin-3-glucuronide was due to deconjugation
      and release of free quercetin. The effect is similar in VSMCs from normotensive
      and hypertensive animals. 

PMID- 25562609
TI  - A very long-term transient event preceding the 2011 Tohoku earthquake.
AB  - Geodetic transients have been observed in various subduction zones. The 2011
      Tohoku earthquake occurred in one of the most active subduction zones globally,
      the Japan Trench subduction zone (JTSZ). However, no geodetic transient (except
      afterslip and so on) had been reported in the JTSZ before the Tohoku earthquake.
      Here we show that a large transient event, with duration longer than any reported
      previously, occurred in the JTSZ preceding the Tohoku earthquake. We calculate
      tectonic deformations at Global Positioning System stations along the JTSZ by
      removing the effects of nearby M(w) 6-8 earthquakes. We identify temporal changes
      in these deformations, deriving 9-year deviation records from regular
      deformations due to slip deficit at the plate boundary. We perform an inversion
      of the deviations to obtain the source model of their root event. The
      relationship between the obtained transient event and Tohoku earthquake is shown
      through Coulomb stress change and seismic supercycle simulation.

PMID- 25562610
TI  - Plasmon resonances of highly doped two-dimensional MoS2.
AB  - The exhibition of plasmon resonances in two-dimensional (2D) semiconductor
      compounds is desirable for many applications. Here, by electrochemically
      intercalating lithium into 2D molybdenum disulfide (MoS2) nanoflakes, plasmon
      resonances in the visible and near UV wavelength ranges are achieved. These
      plasmon resonances are controlled by the high doping level of the nanoflakes
      after the intercalation, producing two distinct resonance peak areas based on the
      crystal arrangements. The system is also benchmarked for biosensing using bovine
      serum albumin. This work provides a foundation for developing future 2D MoS2
      based biological and optical units. 

PMID- 25562608
TI  - Combination of low level light therapy and nitrosyl-cobinamide accelerates wound
      healing.
AB  - Low level light therapy (LLLT) has numerous therapeutic benefits, including
      improving wound healing, but the precise mechanisms involved are not well
      established; in particular, the underlying role of cytochrome C oxidase (C-ox) as
      the primary photoacceptor and the associated biochemical mechanisms still require
      further investigation. We previously showed the nitric oxide (NO) donating drug
      nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent
      protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and
      NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT
      enhanced wound healing proceeded through an electron transport chain-C-ox
      dependent mechanism with a reduction of reactive oxygen species and increased
      adenosine triphosphate production. C-ox was validated as the primary
      photoacceptor by three observations: increased oxygen consumption, reduced wound
      healing in the presence of sodium azide, and disassociation of cyanide, a known C
      ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound
      healing through two independent mechanisms, the electron transport chain-C-ox
      pathway and cGMP signaling, respectively, with both resulting in ERK1/2
      activation.

PMID- 25562611
TI  - Photocatalytic reduction of CO2 over platinised Bi2WO6-based materials.
AB  - The photocatalytic reduction of CO2 with H2O to produce CH4 in the gas phase was
      carried out in the presence of two Bi2WO6-based materials. For this purpose,
      single Bi2WO6 and a coupled Bi2WO6-TiO2 system were synthesised and metallised
      with Pt, through a Pt photodeposition method. Then, the samples were
      characterised and the photocatalytic activity was evaluated in a continuous
      fluidised-bed reactor irradiated with UV light. Single Bi2WO6 presents an
      interesting behaviour under H2O rich conditions. In particular, the metallisation
      improves the material's performance for CH4 formation, while the TiO2 addition to
      Bi2WO6 increases the CH4 yield only at low H2O/CO2 ratio. The Bi2WO6-TiO2 system
      metallised with a Pt photocatalyst displayed the highest CH4 yield among all the
      prepared photocatalysts. The stability of the system can be enhanced through the
      addition of a blue phosphor to the reactant mixture, especially under H2O rich
      conditions. 

PMID- 25562612
TI  - Selective selenol fluorescent probes: design, synthesis, structural determinants,
      and biological applications.
AB  - Selenium (Se) is an essential micronutrient element, and the biological
      significance of Se is predominantly dependent on its incorporation as
      selenocysteine (Sec), the genetically encoded 21st amino acid in protein
      synthesis, into the active site of selenoproteins, which have broad functions,
      ranging from redox regulation and anti-inflammation to the production of active
      thyroid hormones. Compared to its counterpart Cys, there are only limited probes
      for selective recognition of Sec, and such selectivity is strictly restricted at
      low pH conditions. We reported herein the design, synthesis, and biological
      evaluations of a series of potential Sec probes based on the mechanism of
      nucleophilic aromatic substitution. After the initial screening, the structural
      determinants for selective recognition of Sec were recapitulated. The follow-up
      studies identified that probe 19 (Sel-green) responds to Sec and other selenols
      with more than 100-fold increase of emission in neutral aqueous solution (pH
      7.4), while there is no significant interference from the biological thiols,
      amines, or alcohols. Sel-green was successfully applied to quantify the Sec
      content in the selenoenzyme thioredoxin reductase and image endogenous Sec in
      live HepG2 cells. With the aid of Sel-green, we further demonstrated that the
      cytotoxicity of different selenocompounds is correlated to their ability
      metabolizing to selenols in cells. To the best of our knowledge, Sel-green is the
      first selenol probe that works under physiological conditions. The elucidation of
      the structure-activity relationship for selective recognition of selenols paves
      the way for further design of novel probes to better understand the pivotal role
      of Sec as well as selenoproteins in vivo. 

PMID- 25562613
TI  - A comparative study of trypsin specificity based on QM/MM molecular dynamics
      simulation and QM/MM GBSA calculation.
AB  - Hydrogen bonding and polar interactions play a key role in identification of
      protein-inhibitor binding specificity. Quantum mechanics/molecular mechanics
      molecular dynamics (QM/MM MD) simulations combined with DFT and semi-empirical
      Hamiltonian (AM1d, RM1, PM3, and PM6) methods were performed to study the
      hydrogen bonding and polar interactions of two inhibitors BEN and BEN1 with
      trypsin. The results show that the accuracy of treating the hydrogen bonding and
      polar interactions using QM/MM MD simulation of PM6 can reach the one obtained by
      the DFT QM/MM MD simulation. Quantum mechanics/molecular mechanics generalized
      Born surface area (QM/MM-GBSA) method was applied to calculate binding affinities
      of inhibitors to trypsin and the results suggest that the accuracy of binding
      affinity prediction can be significantly affected by the accurate treatment of
      the hydrogen bonding and polar interactions. In addition, the calculated results
      also reveal the binding specificity of trypsin: (1) the amidinium groups of two
      inhibitors generate favorable salt bridge interaction with Asp189 and form
      hydrogen bonding interactions with Ser190 and Gly214, (2) the phenyl of
      inhibitors can produce favorable van der Waals interactions with the residues
      His58, Cys191, Gln192, Trp211, Gly212, and Cys215. This systematic and
      comparative study can provide guidance for the choice of QM/MM MD methods and the
      designs of new potent inhibitors targeting trypsin. 

PMID- 25562614
TI  - The insulin-like factor 3 (INSL3)-receptor (RXFP2) network functions as a germ
      cell survival/anti-apoptotic factor in boar testes.
AB  - Relaxin-like factor, commonly known as insulin-like factor (INSL3), is essential
      for testis descent during fetal development; however, its function in the adult
      testis is still being elucidated. The study aimed to identify a relaxin family
      peptide receptor 2 (RXFP2)-specific antibody suitable for immunological
      approaches, analyze which testicular germ cell types express RXFP2, and clarify
      its expression dynamics in the boar testis. In addition, the function of INSL3
      RXFP2 signaling on the germ cells was explored by neutralizing INSL3 using long
      term active immunization. Samples were collected from Duroc boars, and a
      commercially available RXFP2-specific antibody directed against the human RXFP2
      endodomain was identified by characterizing its specificity in HEK-293 cells
      expressing mouse RXFP2, and by demonstrating the suitability for analyzing RXFP2
      expression in porcine tissues. RXFP2 mRNA and protein were both localized mainly
      in meiotic and post-meiotic germ cells, but not in Leydig cells. Functional
      RXFP2, which enables INSL3 to bind, was detected as an ~85-kDa band, which
      increased in intensity from the pubertal stage onward. Interestingly, INSL3
      immunization significantly reduced testis weight and induced a 4-fold increase in
      the frequency of apoptotic germ cells, which was associated with the up
      regulation of pro-apoptotic caspase-3 (CASP3) and BAX, and the down-regulation of
      anti-apoptotic XIAP and BCL2, and a substantial reduction in sperm concentration.
      These results revealed that RXFP2 was expressed in boar meiotic and post-meiotic
      germ cells, where INSL3 neutralization led to increased germ cell apoptosis and
      reduced sperm output, suggesting that INSL3 acts as a survival/anti-apoptotic
      factor in maintaining sperm production. 

PMID- 25562615
TI  - Oxytocin treatment prevents the cardiomyopathy observed in obese diabetic male
      db/db mice.
AB  - Oxytocin (OT) is involved in the regulation of energy metabolism and in the
      activation of cardioprotective mechanisms. We evaluated whether chronic treatment
      with OT could prevent the metabolic and cardiac abnormalities associated with
      diabetes and obesity using the db/db mice model. Four-week-old male db/db mice
      and their lean nondiabetic littermates (db/+) serving as controls were treated
      with OT (125 ng/kg . h) or saline vehicle for a period of 12 weeks. Compared with
      db/+ mice, the saline-treated db/db mice developed obesity, hyperglycemia, and
      hyperinsulinemia. These mice also exhibited a deficient cardiac OT/natriuretic
      system and developed systolic and diastolic dysfunction resulting from
      cardiomyocyte hypertrophy, fibrosis, and apoptosis. These abnormalities were
      associated with increased reactive oxygen species (ROS) production, inflammation,
      and suppressed 5'-adenosine monophosphate kinase signaling pathway. The db/db
      mice displayed reduced serum levels of adiponectin and adipsin and elevated
      resistin. OT treatment increased circulating OT levels, significantly reduced
      serum resistin, body fat accumulation (19%; P<.001), fasting blood glucose levels
      by (23%; P<.001), and improved glucose tolerance and insulin sensitivity. OT also
      normalized cardiac OT receptors, atrial natriuretic peptide, and brain
      natriuretic peptide, expressions and prevented systolic and diastolic dysfunction
      as well as cardiomyocyte hypertrophy, fibrosis, and apoptosis. Furthermore, OT
      reduced cardiac oxidative stress and inflammation and normalized the 5'-adenosine
      monophosphate-activated protein kinase signaling pathway. The complete
      normalization of cardiac structure and function by OT treatment in db/db mice
      contrasted with only partial improvement of hyperglycemia and hyperinsulinemia.
      These results indicate that chronic treatment with OT partially improves glucose
      and fat metabolism and reverses abnormal cardiac structural remodeling,
      preventing cardiac dysfunction in db/db mice.

PMID- 25562616
TI  - Prevention and reversal of lipotoxicity-induced hepatic insulin resistance and
      steatohepatitis in mice by an antioxidant carotenoid, beta-cryptoxanthin.
AB  - Excessive hepatic lipid accumulation promotes macrophages/Kupffer cells
      activation, resulting in exacerbation of insulin resistance and progression of
      nonalcoholic steatohepatitis (NASH). However, few promising treatment modalities
      target lipotoxicity-mediated hepatic activation/polarization of macrophages for
      NASH. Recent epidemiological surveys showed that serum beta-cryptoxanthin, an
      antioxidant carotenoid, was inversely associated with the risks of insulin
      resistance and liver dysfunction. In the present study, we first showed that beta
      cryptoxanthin administration ameliorated hepatic steatosis in high-fat diet
      induced obese mice. Next, we investigated the preventative and therapeutic
      effects of beta-cryptoxanthin using a lipotoxic model of NASH: mice fed a high
      cholesterol and high-fat (CL) diet. After 12 weeks of CL diet feeding, beta
      cryptoxanthin administration attenuated insulin resistance and excessive hepatic
      lipid accumulation and peroxidation, with increases in M1-type
      macrophages/Kupffer cells and activated stellate cells, and fibrosis in CL diet
      induced NASH. Comprehensive gene expression analysis showed that beta
      cryptoxanthin down-regulated macrophage activation signal-related genes
      significantly without affecting most lipid metabolism-related genes in the liver.
      Importantly, flow cytometry analysis revealed that, on a CL diet, beta
      cryptoxanthin caused a predominance of M2 over M1 macrophage populations, in
      addition to reducing total hepatic macrophage and T-cell contents. In parallel,
      beta-cryptoxanthin decreased lipopolysaccharide-induced M1 marker mRNA expression
      in peritoneal macrophages, whereas it augmented IL-4-induced M2 marker mRNA
      expression, in a dose-dependent manner. Moreover, beta-cryptoxanthin reversed
      steatosis, inflammation, and fibrosis progression in preexisting NASH in mice. In
      conclusion, beta-cryptoxanthin prevents and reverses insulin resistance and
      steatohepatitis, at least in part, through an M2-dominant shift in
      macrophages/Kupffer cells in a lipotoxic model of NASH.

PMID- 25562617
TI  - Prolonged TSH receptor A subunit immunization of female mice leads to a long-term
      model of Graves' disease, tachycardia, and cardiac hypertrophy.
AB  - A transient model for human Graves' disease was successfully established in mice
      using up to 3 immunizations with recombinant adenovirus expressing the
      extracellular A-subunit of the human TSH receptor (TSHR) (Ad-TSHR). We studied
      extension of adenovirally induced TSHR A-subunit immunization in mice by using a
      novel protocol of long-term 3- and 4-weekly injections. Generation of TSHR
      binding stimulatory antibodies (capacity to stimulate cAMP activity in TSHR
      expressing test cells), goiter, and histological thyroid alterations were
      maintained for at least 9 months in all Ad-TSHR-immunized mice. In response to
      injection of 10(10) plaque-forming units of Ad-TSHR, also elevated mean serum T4
      levels were observed throughout the study. Moreover, cardiac organ involvement
      (tachycardia and hypertrophy) were consistently observed in these mice. Higher
      doses of Ad-TSHR (10(11) plaque-forming units) did not produce consistent
      elevation of T4 and were not associated with a clear increase in heart rate vs
      controls, probably because these high doses provoked an immune response-induced
      tachycardia on their own. In summary, a long-term model of Graves' disease
      induced by a relatively simple protocol of continuing monthly immunizations
      should allow to investigate long-term disease mechanisms and may possibly obviate
      the need for more complicated disease models. Moreover, the clinical outcome
      predictor of tachycardia and cardiac involvement was reliably detected in the
      model. 

PMID- 25562619
TI  - Thermoresponsive self-assembled cyclodextrin-end-decorated PNIPAM for aqueous
      catalysis.
AB  - The catalytic performance of thermoresponsive poly(N-isopropylacrylamide)
      (PNIPAM) functionalized at the terminal position with randomly methylated beta
      cyclodextrin was demonstrated by the aqueous Rh-catalysed hydroformylation of
      higher olefins. 

PMID- 25562620
TI  - Merging asymmetric Henry reaction with organocatalytic cascade reaction for the
      construction of a chiral indolizidine alkaloid skeleton.
AB  - A sequential reaction combining the copper-catalyzed asymmetric Henry reaction
      with the organocatalytic Michael addition-hemiacetalization cascade reaction was
      developed. The C1-symmetric chiral diamine L1-copper complex was responsible for
      the first highly enantioselective Henry reaction, while diphenylprolinol silyl
      ether A acted as effective organocatalyst for the second cascade reaction between
      chiral beta-nitro alcohol and alpha,beta-unsaturated aldehydes. Via rational
      design and combination of the two independent catalytic systems, good yields and
      excellent enantioselectivities and diastereoselectivities were achieved for a
      broad substrate scope under mild reaction conditions. The synthetic utility of
      this sequential catalytic asymmetric cascade reaction was demonstrated as an
      alternative and straightforward stereoselective synthesis strategy for chiral
      indolizidine alkaloid and its analogues. 

PMID- 25562618
TI  - Anti-atherosclerotic and anti-inflammatory actions of sesame oil.
AB  - Atherosclerosis, a major form of cardiovascular disease, has now been recognized
      as a chronic inflammatory disease. Nonpharmacological means of treating chronic
      diseases have gained attention recently. We previously reported that sesame oil
      has anti-atherosclerotic properties. In this study, we have determined the
      mechanisms by which sesame oil might modulate atherosclerosis by identifying
      genes and inflammatory markers. Low-density lipoprotein receptor knockout (LDLR(
      /-)) female mice were fed with either an atherogenic diet or an atherogenic diet
      reformulated with sesame oil (sesame oil diet). Plasma lipids and atherosclerotic
      lesions were quantified after 3 months of feeding. Plasma samples were used for
      cytokine analysis. RNA was extracted from the liver tissue and used for global
      gene arrays. The sesame oil diet significantly reduced atherosclerotic lesions,
      plasma cholesterol, triglyceride, and LDL cholesterol levels in LDLR(-/-) mice.
      Plasma inflammatory cytokines, such as MCP-1, RANTES, IL-1alpha, IL-6, and CXCL
      16, were significantly reduced, demonstrating an anti-inflammatory property of
      sesame oil. Gene array analysis showed that sesame oil induced many genes,
      including ABCA1, ABCA2, APOE, LCAT, and CYP7A1, which are involved in cholesterol
      metabolism and reverse cholesterol transport. In conclusion, our studies suggest
      that a sesame oil-enriched diet could be an effective nonpharmacological
      treatment for atherosclerosis by controlling inflammation and regulating lipid
      metabolism.

PMID- 25562621
TI  - Sad and happy emotion discrimination in music by children with cochlear implants.
AB  - Children using cochlear implants (CIs) develop speech perception but have
      difficulty perceiving complex acoustic signals. Mode and tempo are the two
      components used to recognize emotion in music. Based on CI limitations, we
      hypothesized children using CIs would have impaired perception of mode cues
      relative to their normal hearing peers and would rely more heavily on tempo cues
      to distinguish happy from sad music. Study participants were children with 13
      right CIs and 3 left CIs (M = 12.7, SD = 2.6 years) and 16 normal hearing peers.
      Participants judged 96 brief piano excerpts from the classical genre as happy or
      sad in a forced-choice task. Music was randomly presented with alterations of
      transposed mode, tempo, or both. When music was presented in original form,
      children using CIs discriminated between happy and sad music with accuracy well
      above chance levels (87.5%) but significantly below those with normal hearing
      (98%). The CI group primarily used tempo cues, whereas normal hearing children
      relied more on mode cues. Transposing both mode and tempo cues in the same
      musical excerpt obliterated cues to emotion for both groups. Children using CIs
      showed significantly slower response times across all conditions. Children using
      CIs use tempo cues to discriminate happy versus sad music reflecting a very
      different hearing strategy than their normal hearing peers. Slower reaction times
      by children using CIs indicate that they found the task more difficult and
      support the possibility that they require different strategies to process emotion
      in music than normal.

PMID- 25562622
TI  - A novel [4 + 3] interpenetrated net containing 7-fold interlocking pseudo-helical
      chains and exceptional catenane-like motifs.
AB  - A novel interpenetrating metal-organic framework, namely
      [Zn(3)L(2)(oba)(3)(H(2)O)(2)].(4)H(2)O (1), has been synthesized under
      hydrothermal conditions. Its structure was determined by single-crystal X-ray
      diffraction analysis and further characterized by elemental analysis, IR, and
      thermogravimetric (TG) analysis. In the structure of 1, the rigid and flexible V
      shaped ligands link Zn(ii) to form a 3D structure where two types of helices and
      four types of pseudo-helical chains containing three pairs of enantiomers and two
      pairs of conformational isomers have been characterized. One such 3D framework
      incorporates six identical networks to form a 7-fold interpenetrated 3D
      framework. From the topological analysis, the Zn(ii) ions act as three- and four
      connected nodes, and oba as well as L are linkers. The framework of compound can
      be classified as a new (6(3))2(6(5).8) topology, which is a novel (3,3,4)
      connected [4 + 3] 7-fold interpenetrating net showing 7-fold interlocking pseudo
      helical chains and a unique catenane-like motif with Hopf links. In addition, the
      luminescence properties of the compound are discussed.

PMID- 25562623
TI  - Follow-up strategies after treatment (large loop excision of the transformation
      zone (LLETZ)) for cervical intraepithelial neoplasia (CIN): Impact of human
      papillomavirus (HPV) test.
AB  - BACKGROUND: Development of cancer of the cervix is a multi-step process as before
      cervical cancer develops, cervical cells undergo changes and become abnormal.
      These abnormalities are called cervical intraepithelial neoplasia (CIN) and are
      associated with increased risk of subsequent invasive cancer of the cervix.
      Oncogenic high-risk human papillomavirus (hrHPV), the causative agent of cervical
      cancer and its precursor lesions, is present in up to one-third of women
      following large loop excision of the transformation zone (LLETZ) treatment and is
      associated with increased risk of residual disease and disease recurrence. HPV
      testing may serve as a surveillance tool for identifying women at higher risk of
      recurrence. High-risk human papillomavirus testing will enable us to identify
      women at increased risk of residual or recurrent CIN and therefore will allow us
      to offer closer surveillance and early treatment, when indicated. OBJECTIVES: *
      To evaluate the effectiveness and safety of hrHPV testing after large loop
      excision of the transformation zone (LLETZ) treatment* To determine optimal
      follow-up management strategies following LLETZ treatment according to hrHPV
      status SEARCH METHODS: We searched the Cochrane Gynacological Cancer Review Group
      Specialised Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), PubMed and PsycINFO up to August 2013. We searched registers
      of clinical trials, abstracts of scientific meetings and reference lists of
      included studies, and we contacted experts in the field. SELECTION CRITERIA: We
      searched for randomised control trials (RCTs) that compared follow-up management
      strategies following LLETZ treatment for CIN. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed whether potentially relevant studies met
      the inclusion criteria. No trials were found; therefore no data were analysed.
      MAIN RESULTS: The search identified 813 references on MEDLINE, 418 on EMBASE, 22
      on CINAHL, 666 on PubMed, 291 on PsycINFO and 145 on CENTRAL. When all references
      were imported into EndNote and duplications were removed, 1348 references
      remained. Initial screening of titles and abstracts of these references revealed
      that 42 references were potentially eligible for this review. After reading the
      full-text versions, we identified no relevant trials comparing hrHPV and cytology
      testing versus cytology testing alone for detecting residual or recurrent disease
      during follow-up to LLETZ treatment of adult women with CIN.We found no evidence
      on the effects of hrHPV and cytology testing on residual or recurrent CIN2 or
      higher lesions, anxiety and psychosexual morbidity outcomes in women undergoing
      colposcopy and treatment for CIN. AUTHORS' CONCLUSIONS: We found no evidence from
      RCTs to inform decisions about the best surveillance strategy for women following
      treatment for CIN. A prognostic systematic review is needed to investigate the
      risk of developing recurrent cervical intraepithelial neoplasia 2+ (CIN2+) in
      women with a positive hrHPV test after large loop excision of the transformation
      zone (LLETZ) treatment.

PMID- 25562625
TI  - Simple quantitative determination of potent thiols at ultratrace levels in wine
      by derivatization and high-performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) analysis.
AB  - Volatile sulfur compounds contribute characteristic aromas to foods and beverages
      and are widely studied, because of their impact on sensory properties. Certain
      thiols are particularly important to the aromas of roasted coffee, cooked meat,
      passion fruit, grapefruit, and guava. These same thiols enhance the aroma
      profiles of different wine styles, imparting pleasant aromas reminiscent of
      citrus and tropical fruits (due to 3-mercaptohexan-1-ol, 3-mercaptohexyl acetate,
      4-mercapto-4-methylpentan-2-one), roasted coffee (2-furfurylthiol), and struck
      flint (benzyl mercaptan), at nanogram-per-liter levels. In contrast to the usual
      gas chromatography (GC) approaches, a simple and unique high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for
      routine analysis of five wine thiols, using 4,4'-dithiodipyridine (DTDP) as a
      derivatizing agent and polydeuterated internal standards for maximum accuracy and
      precision. DTDP reacted rapidly with thiols at wine pH and provided stable
      derivatives, which were enriched by solid-phase extraction (SPE) prior to
      analysis by HPLC-MS/MS. All steps were optimized and the method was validated in
      different wine matrices, with method performance being comparable to a well
      optimized but more cumbersome gas chromatography-mass spectrometry (GC-MS)
      method. A range of commercial wines was analyzed with the new method, revealing
      the distribution of the five thiols in white, red, rose, and sparkling wine
      styles. 

PMID- 25562626
TI  - Fast pyrolysis of 13C-labeled cellobioses: gaining insights into the mechanisms
      of fast pyrolysis of carbohydrates.
AB  - A fast-pyrolysis probe/tandem mass spectrometer combination was utilized to
      determine the initial fast-pyrolysis products for four different selectively
      (13)C-labeled cellobiose molecules. Several products are shown to result entirely
      from fragmentation of the reducing end of cellobiose, leaving the nonreducing end
      intact in these products. These findings are in disagreement with mechanisms
      proposed previously. Quantum chemical calculations were used to identify feasible
      low-energy pathways for several products. These results provide insights into the
      mechanisms of fast pyrolysis of cellulose. 

PMID- 25562627
TI  - Association of the NQO1 C609T polymorphism with Alzheimer's disease in Chinese
      populations: a meta-analysis.
AB  - Several molecular genetics studies have investigated the association of NQO1
      C609T polymorphism with Alzheimer's disease (AD) susceptibility in Chinese
      populations; however, the findings are inconclusive. To investigate the
      association, we performed the present meta-analysis of 5 case-control studies
      (including 735 AD cases and 828 controls). We searched literature from PubMed,
      Embase, HuGNet and CNKI databases for eligible articles that evaluated the
      association between NQO1 C609T polymorphism and AD risk. We used odds ratios
      (ORs) with 95% confidence intervals (CIs) to evaluate the strength of the
      association. Overall, C609T polymorphism was significantly associated with an
      increased AD risk (homozygote: OR = 1.87, 95% CI = 1.39-2.51, P = 0.000;
      heterozygote: OR = 1.93, 95% CI = 1.22-3.06, P = 0.019; dominant: OR = 1.97, 95%
      CI = 1.25-3.12, P = 0.004). When stratified by source of control, significant
      results were observed in subjects of population-based (PB), whereas no increased
      risk was observed among the hospital-based (HB). When stratified by APOEepsilon4
      carrier status, no effect of the NQO1 C609T polymorphism was seen in subjects of
      APOEepsilon4 carriers and APOEepsilon4 non-carriers. In conclusion, our results
      showed that NQO1 C609T polymorphism increases the risk of AD in Chinese
      populations. Larger studies with different ethnic populations are required to
      validate our findings. 

PMID- 25562624
TI  - Pigment epithelium-derived factor inhibits retinal microvascular dysfunction
      induced by 12/15-lipoxygenase-derived eicosanoids.
AB  - We recently demonstrated that 12/15-lipoxygenase (LOX) derived metabolites,
      hydroxyeicosatetraenoic acids (HETEs), contribute to diabetic retinopathy (DR)
      via NADPH oxidase (NOX) and disruption of the balance in retinal levels of the
      vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor
      (PEDF). Here, we test whether PEDF ameliorates retinal vascular injury induced by
      HETEs and the underlying mechanisms. Furthermore, we pursue the causal
      relationship between LOX-NOX system and regulation of PEDF expression during DR.
      For these purposes, we used an experimental eye model in which normal mice were
      injected intravitreally with 12-HETE with/without PEDF. Thereafter, fluorescein
      angiography (FA) was used to evaluate the vascular leakage, followed by optical
      coherence tomography (OCT) to assess the presence of angiogenesis. FA and OCT
      reported an increased vascular leakage and pre-retinal neovascularization,
      respectively, in response to 12-HETE that were not observed in the PEDF-treated
      group. Moreover, PEDF significantly attenuated the increased levels of vascular
      cell and intercellular adhesion molecules, VCAM-1 and ICAM-1, elicited by 12-HETE
      injection. Accordingly, the direct relationship between HETEs and PEDF has been
      explored through in-vitro studies using Muller cells (rMCs) and human retinal
      endothelial cells (HRECs). The results showed that 12- and 15-HETEs triggered the
      secretion of TNF-alpha and IL-6, as well as activation of NFkappaB in rMCs and
      significantly increased permeability and reduced zonula occludens protein-1 (ZO
      1) immunoreactivity in HRECs. All these effects were prevented in PEDF-treated
      cells. Furthermore, interest in PEDF regulation during DR has been expanded to
      include NOX system. Retinal PEDF was significantly restored in diabetic mice
      treated with NOX inhibitor, apocynin, or lacking NOX2 up to 80% of the control
      level. Collectively, our findings suggest that interfering with LOX-NOX signaling
      opens up a new direction for treating DR by restoring endogenous PEDF that
      carries out multilevel vascular protective functions. 

PMID- 25562629
TI  - PTHrP regulates water absorption and aquaporin expression in the intestine of the
      marine sea bream (Sparus aurata, L.).
AB  - Water ingestion by drinking is fundamental for ion homeostasis in marine fish.
      However, the fluid ingested requires processing to allow net water absorption in
      the intestine. The formation of luminal carbonate aggregates impacts on calcium
      homeostasis and requires epithelial HCO3(-) secretion to enable water absorption.
      In light of its endocrine importance in calcium handling and the indication of
      involvement in HCO3(-) secretion the present study was designed to expose the
      role of the parathyroid hormone-related protein (PTHrP) in HCO3(-) secretion,
      water absorption and the regulation of aqp1 gene expression in the anterior
      intestine of the sea bream. HCO3(-) secretion rapidly decreased when PTHrP(1-34)
      was added to anterior intestine of the sea bream mounted in Ussing chambers. The
      effect achieved a maximum inhibition of 60% of basal secretion rates, showing a
      threshold effective dose of 0.1 ng ml(-1) compatible with reported plasma values
      of PTHrP. When applied in combination with the adenylate cyclase inhibitor (SQ
      22.536, 100 MUmol l(-1)) or the phospholipase C inhibitor (U73122, 10 MUmol l(
      1)) the effect of PTHrP(1-34) on HCO3(-) secretion was reduced by about 50% in
      both cases. In parallel, bulk water absorption measured in intestinal sacs was
      sensitive to inhibition by PTHrP. The inhibitory action conforms to a typical
      dose-response curve in the range of 0.1-1000 ng ml(-1), achieves a maximal effect
      of 60-65% inhibition from basal rates and shows threshold significant effects at
      hormone levels of 0.1 ng ml(-1). The action of PTHrP in water absorption was
      completely abolished in the presence of the adenylate cyclase inhibitor (SQ
      22.536, 100 MUmol l(-1)) and was insensitive to the phospholipase C inhibitor
      (U73122, 10 MUmol l(-1)). In vivo injections of PTHrP(1-34) or the PTH/PTHrP
      receptor antagonist PTHrP(7-34) evoked respectively, a significant decrease or
      increase of aqp1ab, but not aqp1a. Overall the present results suggest that PTHrP
      acts as a key regulator of carbonate aggregate formation in the intestine of
      marine fish via its actions on water absorption, calcium regulation and HCO3(-)
      secretion.

PMID- 25562628
TI  - Male reproductive success is correlated with testosterone in the eastern black
      rhinoceros (Diceros bicornis michaeli).
AB  - Among natural populations of polygynous species, males often vary in their
      lifetime reproductive success. However, in managed populations of endangered
      species, either in situ or as part of captive breeding programmes, it is
      important to understand why differences in reproductive success occur. The
      European captive population of the critically endangered eastern black rhinoceros
      is currently under-performing relative to their wild counterparts, with low
      reproductive output and high reproductive skew limiting growth and genetic
      diversity. To investigate why over 40% of captive males fail to breed, faecal
      samples were collected weekly from 23 males at 12 institutions across Europe for
      4-32 months. Testosterone metabolite concentration was compared between proven
      and non-proven males and a number of intrinsic and extrinsic factors that could
      influence reproductive success were also investigated. Males that sired within
      the last 31/2 years had significantly higher androgen concentrations than non
      proven males, and average testosterone was positively correlated with the number
      of offspring sired per year spent in the reproductive age class. Proven and non
      proven males did not differ in their body condition, or in average faecal
      glucocorticoid concentration. Differences in individual temperament were
      associated with adrenal activity, but did not correlate with reproductive
      category. Highest testosterone concentrations were observed in proven males that
      were housed with females during oestrus, and lowest concentrations in non-proven
      females not housed with females at all during the study period. Further work is
      necessary to determine whether proven males had higher testosterone due to
      underlying differences associated with quality, or whether external stimuli such
      as access to females could influence testosterone concentration and increase a
      male's chances of becoming a successful breeder.

PMID- 25562631
TI  - Preconditioning effect of (S)-3,5-dihydroxyphenylglycine on ischemic injury in
      middle cerebral artery occluded Sprague-Dawley rats.
AB  - Glutamate receptors are the integral cellular components associated with
      excitotoxicity mechanism induced by the ischemic cascade events. Therefore the
      glutamate receptors have become the major molecular targets of neuroprotective
      agents in stroke researches. Recent studies have demonstrated that a Group I
      metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine ((S)-3,5
      DHPG) preconditioning elicits neuroprotection in the hippocampal slice cultures
      exposed to toxic level of N-methyl-d-aspartate (NMDA). We further investigated
      the preconditioning effects of (S)-3,5-DHPG on acute ischemic stroke rats. One 10
      or 100MUM of (S)-3,5-DHPG was administered intrathecally to Sprague-Dawley adult
      male rats, 2h prior to induction of acute ischemic stroke by middle cerebral
      artery occlusion (MCAO). After 24h, neurological deficits were evaluated by
      modified stroke severity scores and grid-walking test. All rats were sacrificed
      and infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride
      staining. The serum level of neuron-specific enolase (NSE) of each rat was
      analyzed by enzyme-linked immunosorbent assay (ELISA). One and 10MUM of (S)-3,5
      DHPG preconditioning in the stroke rats showed significant improvements in motor
      impairment (P<0.01), reduction in the infarct volume (P<0.01) and reduction in
      the NSE serum level (P<0.01) compared to the control stroke rats. We conclude
      that 1 and 10MUM (S)-3,5-DHPG preconditioning induced protective effects against
      acute ischemic insult in vivo. 

PMID- 25562630
TI  - Protective effect of carnosine on febrile seizures in immature mice.
AB  - Febrile seizures (FSs) are the most common type of convulsions in childhood and
      complex FSs represent an increased risk for development of temporal lobe
      epilepsy. The aim of this study was to analyze the anticonvulsant effects of
      carnosine, an endogenous dipeptide composed of alanine and histidine, on
      hyperthermia induced seizure in immature mice. Injection of carnosine
      significantly increased the latency and decreased the duration of FSs in a dose
      dependent manner. In addition, histidine had similar effects on FSs as carnosine.
      The protective effect of carnosine or histidine was completely abolished by alpha
      fluoromethylhistidine (alpha-FMH), a selective and irreversible histidine
      decarboxylase inhibitor, or in histidine decarboxylase deficient (HDC-KO) mice.
      Peripheral carnosine administration increased the level of carnosine, histidine
      and histamine in the cortex and hippocampus of mice pups, but decreased glutamate
      contents in the cortex and hippocampus. These results indicate that carnosine can
      protect against FSs in mice pups through its conversion to histamine, suggesting
      that it may serve as an efficient anti-FSs drug in the future. 

PMID- 25562632
TI  - Visuo-locomotor coordination for direction changes in a manual wheelchair as
      compared to biped locomotion in healthy subjects.
AB  - The visual system during walking provides travel path and environmental
      information. Although the manual wheelchair (MWC) is also a frequent mode of
      locomotion, its underlying visuo-locomotor control is not well understood. This
      study begins to understand the visuo-locomotor coordination for MWC navigation in
      relation to biped gait during direction changes in healthy subjects. Eight
      healthy male subjects (26.9+/-6.4 years) were asked to walk as well as to propel
      a MWC straight ahead and while changing direction by 45 degrees  to the right
      guided by a vertical pole. Body and MWC movement (speed, minimal clearance, point
      of deviation, temporal body coordination, relative timing of body rotations) and
      gaze behavior were analysed. There was a main speed effect for direction and a
      direction by mode interaction with slower speeds for MWC direction change. Point
      of deviation was later for MWC direction change and always involved a counter
      movement (seen for vehicular control) with greater minimal distance from the
      vertical pole as compared to biped gait. In straight ahead locomotion, subjects
      predominantly fixed their gaze on the end target for both locomotor modes while
      there was a clear trend for subjects to fixate on the vertical pole more for MWC
      direction change. When changing direction, head movement always preceded gaze
      changes, which was followed by trunk movement for both modes. Yet while subjects
      turned the trunk at the same time during approach regardless of locomotor mode,
      head movement was earlier for MWC locomotion. These results suggest that MWC
      navigation combines both biped locomotor and vehicular-based movement control.
      Head movement to anticipate path deviations and lead steering for locomotion
      appears to be stereotypic across locomotor modes, while specific gaze behavior
      predominantly depends on the environmental demands. 

PMID- 25562633
TI  - The mouse/human cross-species heterodimer of leucine-rich repeat kinase 2:
      possible significance in the transgenic model mouse of Parkinson's disease.
AB  - Leucine-rich repeat kinase (LRRK2) is the causal molecule of autosomal dominant
      Parkinson's disease (PD). We previously reported that intracellular degradation
      of wild-type (WT) LRRK2 is promoted by formation of heterodimers with the I2020T
      mutant LRRK2. In the present study, we investigated whether this is also the case
      for mouse/human cross-species heterodimers, which could be formed in transgenic
      mice. First, by co-transfection and immunoprecipitation, we identified the cross
      species heterodimer of mouse LRRK2 and human LRRK2. Next, we found that the
      protein level of mouse LRRK2 decreased when co-transfected with human I2020T
      LRRK2, but not with human WT LRRK2. These results suggested that degradation of
      mouse LRRK2 was promoted by formation of a cross-species heterodimer with the
      mutant LRRK2. In I2020T LRRK2-transgenic mice, the lower protein level of brain
      LRRK2 in comparison with control mice, together with higher expression of the
      mRNA, suggested that endogenous LRRK2 was degraded by formation of cross-species
      heterodimers. Our results suggest a new concept of cross-species dimer/oligomer
      formation in transgenic disease-model mice. 

PMID- 25562635
TI  - Transparent conductive oxide films embedded with plasmonic nanostructure for
      light-emitting diode applications.
AB  - In this study, a spin coating process in which the grating structure comprises an
      Ag nanoparticle layer coated on a p-GaN top layer of InGaN/GaN light-emitting
      diode (LED) was developed. Various sizes of plasmonic nanoparticles embedded in a
      transparent conductive layer were clearly observed after the deposition of indium
      tin oxide (ITO). The plasmonic nanostructure enhanced the light extraction
      efficiency of blue LED. Output power was 1.8 times the magnitude of that of
      conventional LEDs operating at 350 mA, but retained nearly the same current
      voltage characteristic. Unlike in previous research on surface-plasmon-enhanced
      LEDs, the metallic nanoparticles were consistently deposited over the surface
      area. However, according to microstructural observation, ITO layer mixed with Ag
      based nanoparticles was distributed at a distance of approximately 150 nm from
      the interface of ITO/p-GaN. Device performance can be improved substantially by
      using the three-dimensional distribution of Ag-based nanoparticles in the
      transparent conductive layer, which scatters the propagating light randomly and
      is coupled between the localized surface plasmon and incident light internally
      trapped in the LED structure through total internal reflection. 

PMID- 25562634
TI  - Precueing time but not direction of postural perturbation induces early muscular
      activation: comparison between young and elderly individuals.
AB  - In this study, we evaluated the effect of precueing characteristics of an
      impending perturbation to upright stance on reactive responses of distal leg
      muscles. Young and older individuals were compared in a task of recovering stable
      upright stance following rotation of the supporting platform to induce anterior
      or posterior body sway. Directions of the supporting platform rotation were
      randomized across trials. Immediately before postural perturbation participants
      were cued about direction and/or time of platform rotation, or performed the task
      under directional and temporal uncertainty of the impending perturbation. Results
      showed that precueing time of perturbation led to earlier muscular activation
      onset, while precueing perturbation direction did not modulate either latency or
      magnitude of muscular activation. Those effects were similar between age groups.
      Our findings suggest that awareness of the perturbation time favored shorter
      response latencies in both the young and older individuals. 

PMID- 25562636
TI  - UV photochemistry of benzene and cyclohexadienyl radical in solid parahydrogen.
AB  - Matrix-isolation spectroscopy in solid parahydrogen is a powerful technique for
      the study of photochemical reactions in detail. It is especially suited for the
      detection of chemical intermediates and unstable molecular products of
      photochemical reactions that are otherwise difficult to observe using other
      conventional spectroscopic techniques. Here, we have revisited UV photochemistry
      of benzene induced by 193 and 253.7 nm excitations by matrix-isolation infrared
      spectroscopy using solid parahydrogen as a host matrix. In addition to the
      formation of benzvalene, fulvene, and Dewar benzene as photoproducts of the UV
      photolysis of benzene, we have confirmed the production of cyclohexadienyl
      radical in solid parahydrogen as an intermediate species for a ring-opening
      reaction to 1,3,5-hexatriene. Moreover, we have identified 1,3-hexadien-5-yne and
      o-benzyne as minor products of the photochemical reaction. The reaction
      mechanisms of these species based on the analysis of FTIR spectra and quantum
      chemical calculations are discussed. 

PMID- 25562637
TI  - Comparison of barbed and conventional sutures in adhesion formation and
      histological features in a rat myomectomy model: randomized single blind
      controlled trial.
AB  - OBJECTIVE: To compare the adhesion and histologic scoring of barbed and standard
      suture material after incision and serosal closure of both uterine horns for
      myomectomy model in rats. STUDY DESIGN: In this single blind randomized
      controlled trial, one cm incisions were performed on the right and left uterine
      horns of ten non-pregnant rats, and these incisions were randomly allocated for
      closure by a suture material with either polyglyconate (V-LocTM) or polyglactin
      910 (Vicryl((r))). Each rat served as its own control. Six weeks after the
      operation, the abdomen was re-opened and the abdominal and surgical sites were
      evaluated by a researcher blinded to the side of the suture materials in the
      first operation. Adhesions were scored according to their severity, and specimens
      were also evaluated and scored histologically according to the following
      features: collagen deposition and inflammatory reaction. RESULTS: The median
      macroscopic adhesion scores in the barbed and standard suture group were 3.5 and
      2, respectively (p=.008). There was significant difference between the barbed and
      standard suture group with regard to the median inflammatory cell scores for
      macrophages-foreign body giant cell (1 vs. 3, respectively, p=.01) and
      mononuclear cell (2 vs. 3, respectively, p=.04). CONCLUSION: Based on the results
      of the present study, we suggest that in the rat model, the type of the suture
      used for myometrial closure has an effect on subsequent adhesion formation, and
      this adverse outcome was more frequently observed with the barbed suture.

PMID- 25562638
TI  - Fluorescence-quenched substrates for live cell imaging of human
      glucocerebrosidase activity.
AB  - Deficiency of the lysosomal glycoside hydrolase glucocerebrosidase (GCase) leads
      to abnormal accumulation of glucosyl ceramide in lysosomes and the development of
      the lysosomal storage disease known as Gaucher's disease. More recently,
      mutations in the GBA1 gene that encodes GCase have been uncovered as a major
      genetic risk factor for Parkinson's disease (PD). Current therapeutic strategies
      to increase GCase activity in lysosomes involve enzyme replacement therapy (ERT)
      and molecular chaperone therapy. One challenge associated with developing and
      optimizing these therapies is the difficulty in determining levels of GCase
      activity present within the lysosomes of live cells. Indeed, visualizing the
      activity of endogenous levels of any glycoside hydrolases, including GCase, has
      proven problematic within live mammalian cells. Here we describe the successful
      modular design and synthesis of fluorescence-quenched substrates for GCase. The
      selection of a suitable fluorophore and quencher pair permits the generation of
      substrates that allow convenient time-dependent monitoring of endogenous GCase
      activity within cells as well as localization of activity within lysosomes. These
      efficiently quenched (~99.9%) fluorescent substrates also permit assessment of
      GCase inhibition in live cells by either confocal microscopy or high content
      imaging. Such substrates should enable improved understanding of GCase in situ as
      well the optimization of small-molecule chaperones for this enzyme. These
      findings also suggest routes to generate fluorescence-quenched substrates for
      other mammalian glycoside hydrolases for use in live cell imaging. 

PMID- 25562639
TI  - Intravenous delivery of camptothecin-loaded PLGA nanoparticles for the treatment
      of intracranial glioma.
AB  - Effective treatment of glioblastoma multiforme remains a major clinical
      challenge, due in part to the difficulty of delivering chemotherapeutics across
      the blood-brain barrier. Systemically administered drugs are often poorly
      bioavailable in the brain, and drug efficacy within the central nervous system
      can be limited by peripheral toxicity. Here, we investigate the ability of
      systemically administered poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs)
      to deliver hydrophobic payloads to intracranial glioma. Hydrophobic payload
      encapsulated within PLGA NPs accumulated at ~10* higher levels in tumor compared
      to healthy brain. Tolerability of the chemotherapeutic camptothecin (CPT) was
      improved by encapsulation, enabling safe administration of up to 20mg/kg drug
      when encapsulated within NPs. Immunohistochemistry staining for gamma-H2AFX, a
      marker for double-strand breaks, demonstrated higher levels of drug activity in
      tumors treated with CPT-loaded NPs compared to free drug. CPT-loaded NPs were
      effective in slowing the growth of intracranial GL261 tumors in immune competent
      C57 albino mice, providing a significant survival benefit compared to mice
      receiving saline, free CPT or low dose CPT NPs (median survival of 36.5 days
      compared to 28, 32, 33.5 days respectively). In sum, these data demonstrate the
      feasibility of treating intracranial glioma with systemically administered
      nanoparticles loaded with the otherwise ineffective chemotherapeutic CPT. 

PMID- 25562640
TI  - Stable carboxylic acid derivatized alkoxy silanes.
AB  - A convenient and straightforward one-pot hydrosilylation reaction of different
      unsaturated carboxylic acids with trialkoxysilanes in the presence of catalytic
      amounts of platinum(IV) dioxide resulted in excellent yields in organofunctional
      silanes combining carboxy- and alkoxy groups within one molecule.

PMID- 25562641
TI  - Tenascin-C in cardiovascular remodeling: potential impact for diagnosis,
      prognosis estimation and targeted therapy.
AB  - Fetal variants of tenascin-C are not expressed in healthy adult myocardium. But,
      there is a relevant re-occurrence during pathologic cardiac tissue and vascular
      remodeling. Thus, these molecules, in particular B and C domain containing
      tenascin-C, might qualify as promising novel biomarkers for diagnosis and
      prognosis estimation. Since a stable extracellular deposition of fetal tenascin-C
      variants is present in diseased cardiac tissue, the molecules are excellent
      target structures for antibody-based delivery of diagnostic (e.g., radionuclides)
      or therapeutic (bioactive payloads) agents directly to the site of disease.
      Against the background that fetal tenascin-C variants are functionally involved
      in cardiovascular tissue remodeling, therapeutic functional blocking strategies
      could be experimentally tested in the future.

PMID- 25562642
TI  - A conversation with Susan Band Horwitz.
AB  - Susan Band Horwitz is a Distinguished Professor and holds the Falkenstein Chair
      in Cancer Research at Albert Einstein College of Medicine in New York. She is co
      chair of the Department of Molecular Pharmacology and associate director for
      therapeutics at the Albert Einstein Cancer Center. After graduating from Bryn
      Mawr College, Dr. Horwitz received her PhD in biochemistry from Brandeis
      University. She has had a continuing interest in natural products as a source of
      new drugs for the treatment of cancer. Her most seminal research contribution has
      been in the development of Taxol((r)). Dr. Horwitz and her colleagues made the
      discovery that Taxol had a unique mechanism of action and suggested that it was a
      prototype for a new class of antitumor drugs. Although Taxol was an antimitotic
      agent blocking cells in the metaphase stage of the cell cycle, Dr. Horwitz
      recognized that Taxol was blocking mitosis in a way different from that of other
      known agents. Her group demonstrated that the binding site for Taxol was on the
      beta-tubulin subunit. The interaction of Taxol with the beta-tubulin subunit
      resulted in stabilized microtubules, essentially paralyzing the cytoskeleton,
      thereby preventing cell division. Dr. Horwitz served as president (2002-2003) of
      the American Association for Cancer Research (AACR). She is a member of the
      National Academy of Sciences, the Institute of Medicine, the American Academy of
      Arts and Sciences, and the American Philosophical Society. She has received
      numerous honors and awards, including the C. Chester Stock Award from Memorial
      Sloan Kettering Cancer Center, the Warren Alpert Foundation Prize from Harvard
      Medical School, the Bristol-Myers Squibb Award for Distinguished Achievement in
      Cancer Research, the American Cancer Society's Medal of Honor, and the AACR Award
      for Lifetime Achievement in Cancer Research. The following interview was
      conducted on January 23, 2014.

PMID- 25562643
TI  - Introduction to the theme "Precision medicine and prediction in pharmacology".

PMID- 25562644
TI  - New approaches to inhibiting platelets and coagulation.
AB  - Ischemic heart disease and stroke are major causes of death and morbidity
      worldwide. Coronary and cerebrovascular events are a consequence of thrombus
      formation caused by atherosclerotic plaque rupture or embolism, both of which
      result from platelet activation and aggregation and thrombin-mediated fibrin
      generation via the coagulation cascade. Current and emerging antiplatelet and
      anticoagulant agents are evolving rapidly. The use of aspirin for primary
      prevention continues to be controversial, as are the doses appropriate for
      secondary prevention. Development of new oral and intravenous adenosine
      diphosphate P2Y12 inhibitors and novel antiplatelet agents continues to transform
      the landscape of antiplatelet therapy. Oral anticoagulation has advanced with the
      use of direct thrombin and factor Xa inhibitors that do not require therapeutic
      monitoring. In this review, we discuss the pharmacology and growing clinical
      evidence for traditional and new antiplatelet and anticoagulant therapies. 

PMID- 25562645
TI  - Designed ankyrin repeat proteins (DARPins): binding proteins for research,
      diagnostics, and therapy.
AB  - Designed ankyrin repeat proteins (DARPins) can recognize targets with
      specificities and affinities that equal or surpass those of antibodies, but
      because of their robustness and extreme stability, they allow a multitude of more
      advanced formats and applications. This review highlights recent advances in
      DARPin design, illustrates their properties, and gives some examples of their
      use. In research, they have been established as intracellular, real-time sensors
      of protein conformations and as crystallization chaperones. For future therapies,
      DARPins have been developed by advanced, structure-based protein engineering to
      selectively induce apoptosis in tumors by uncoupling surface receptors from their
      signaling cascades. They have also been used successfully for retargeting
      viruses. In ongoing clinical trials, DARPins have shown good safety and efficacy
      in macular degeneration diseases. These developments all ultimately exploit the
      high stability, solubility, and aggregation resistance of these molecules,
      permitting a wide range of conjugates and fusions to be produced and purified. 

PMID- 25562647
TI  - Nonstraight nanochannels transfer water faster than straight nanochannels.
AB  - Understanding the flow of liquids and particularly water in nanochannels is
      important for scientific and technological applications, such as for filtration
      and drug delivery. Here we perform molecular dynamics simulations to investigate
      the transfer of single-file water molecules across straight or nonstraight single
      walled carbon nanotubes (SWCNTs). In contrast with the macroscopic scenario, the
      nonstraight nanostructure can increase the water permeation. Remarkably, compared
      with the straight SWCNT, the nonstraight SWCNT with the minimal bending angle of
      35 degrees  in the simulations can enhance the water transport up to 3.5 times.
      This enhancement mainly originates from the Lennard-Jones interaction between
      water molecules and nonstraight nanostructures. Our work offers an additional
      freedom to design high-flux nanochannels by choosing nonstraight nanostructures
      and provides an insight into water flow across biological water nanochannels,
      which are often nonstraight since they are composed of integral membrane
      proteins. 

PMID- 25562648
TI  - Versatile lock and key assembly for optical measurements with microfluidic
      platforms and cartridges.
AB  - A novel and versatile optical reader for microfluidic platforms is presented. The
      reader includes a modular insertion port based on the lock and key concept for
      reproducible alignment with a miniaturized optical detection system comprising an
      interchangeable light emitting diode (LED) and a photodiode. The modular nature
      of the insertion port allows the use of microfluidic platforms in variable shapes
      and fluidic configurations. Three different analytical methodologies based on
      absorbance or fluorescence measurements were used to demonstrate the flexibility
      and reproducibility of the proposed experimental setup. 

PMID- 25562646
TI  - Constellation pharmacology: a new paradigm for drug discovery.
AB  - Constellation pharmacology is a cell-based high-content phenotypic-screening
      platform that utilizes subtype-selective pharmacological agents to elucidate the
      cell-specific combinations (constellations) of key signaling proteins that define
      specific cell types. Heterogeneous populations of native cells, in which the
      different individual cell types have been identified and characterized, are the
      foundation for this screening platform. Constellation pharmacology is useful for
      screening small molecules or for deconvoluting complex mixtures of biologically
      active natural products. This platform has been used to purify natural products
      and discover their molecular mechanisms. In the ongoing development of
      constellation pharmacology, there is a positive feedback loop between the
      pharmacological characterization of cell types and screening for new drug
      candidates. As constellation pharmacology is used to discover compounds with
      novel targeting-selectivity profiles, those new compounds then further help to
      elucidate the constellations of specific cell types, thereby increasing the
      content of this high-content platform. 

PMID- 25562649
TI  - "Just caring": can we afford the ethical and economic costs of circumventing
      cancer drug resistance?
AB  - Personalized medicine has been presented in public and professional contexts in
      excessively optimistic tones. In the area of cancer what has become clear is the
      extraordinary heterogeneity and resilience of tumors in the face of numerous
      targeted therapies. This is the problem of cancer drug resistance. I summarize
      this problem in the first part of this essay. I then place this problem in the
      context of the larger political economic problem of escalating health care costs
      in both the EU and the US. In turn, that needs to be placed within an ethical
      context: How should we fairly distribute access to needed health care for an
      enormous range of health care needs when we have only limited resources (money)
      to meet virtually unlimited health care needs (cancer and everything else)? This
      is the problem of health care rationing. It is inescapable as a moral problem and
      requires a just resolution. Ultimately that resolution must be forged through a
      process of rational democratic deliberation. 

PMID- 25562651
TI  - Effect model law: an approach for the implementation of personalized medicine.
AB  - The effect model law states that a natural relationship exists between the
      frequency (observation) or the probability (prediction) of a morbid event without
      any treatment and the frequency or probability of the same event with a
      treatment. This relationship is called the effect model. It applies to a single
      individual, individuals within a population, or groups. In the latter case,
      frequencies or probabilities are averages of the group. The relationship is
      specific to a therapy, a disease or an event, and a period of observation. If one
      single disease is expressed through several distinct events, a treatment will be
      characterized by as many effect models. Empirical evidence, simulations with
      models of diseases and therapies and virtual populations, as well as theoretical
      derivation support the existence of the law. The effect model could be estimated
      through statistical fitting or mathematical modelling. It enables the prediction
      of the (absolute) benefit of a treatment for a given patient. It thus constitutes
      the theoretical basis for the design of practical tools for personalized
      medicine. 

PMID- 25562652
TI  - Examining the Relationship between Choice, Therapeutic Alliance and Outcomes in
      Mental Health Services.
AB  - BACKGROUND: Self-determination within mental health services is increasingly
      recognized as an ethical imperative, but we still know little about the impact of
      choice on outcomes among people with severe mental illnesses. This study examines
      whether choice predicts outcomes and whether this relationship is mediated by
      therapeutic alliance. METHOD: The study sample of 396 participants completed a
      survey measuring choice, therapeutic alliance, recovery, quality of life and
      functioning. Multivariate analyses examined choice as a predictor of outcomes,
      and Sobel tests assessed alliance as a mediator. RESULTS: Choice variables
      predicted recovery, quality of life and perceived outcomes. Sobel tests indicated
      that the relationship between choice and outcome variables was mediated by
      therapeutic alliance. IMPLICATIONS: The study demonstrates that providing more
      choice and opportunities for collaboration within services does improve consumer
      outcomes. The results also show that collaboration is dependent on the quality of
      the relationship between the provider and consumer.

PMID- 25562654
TI  - Identification of a novel cell-penetrating peptide targeting human glioblastoma
      cell lines as a cancer-homing transporter.
AB  - Cell-penetrating peptides (CPPs) as a novel biomedical delivery system have been
      highly anticipated, since they can translocate across biological membranes and
      are capable of transporting their cargo inside live cells with minimal
      invasiveness. However, non-selective internalization in various cell types
      remains a challenge in the clinical application of CPPs, especially in cancer
      treatment. In this study, we attempted to identify novel cancer-homing CPPs to
      target glioblastoma multiforme (GBM), which is often refractory and resistant to
      treatment. We screened for CPPs showing affinity for the human GBM cell line,
      U87MG, from an mRNA display random peptide library. One of the candidate peptides
      which amino-acid sequence was obtained from the screening showed selective cell
      penetrating activity in U87MG cells. Conjugation of the p16(INK4a) functional
      peptide to the GBM-selective CPP induced cellular apoptosis and reduced
      phosphorylated retinoblastoma protein levels. This indicates that the CPP was
      capable of delivering a therapeutic molecule into U87MG cells inducing apoptosis.
      These results suggest that the novel CPP identified in this study permeates with
      high affinity into GBM cells, revealing it to be a promising imaging and
      therapeutic tool in the treatment of glioblastoma. 

PMID- 25562653
TI  - Open access integrated therapeutic and diagnostic platforms for personalized
      cardiovascular medicine.
AB  - It is undeniable that the increasing costs in healthcare are a concern. Although
      technological advancements have been made in healthcare systems, the return on
      investment made by governments and payers has been poor. The current model of
      care is unsustainable and is due for an upgrade. In developed nations, a law of
      diminishing returns has been noted in population health standards, whilst in the
      developing world, westernized chronic illnesses, such as diabetes and
      cardiovascular disease have become emerging problems. The reasons for these
      trends are complex, multifactorial and not easily reversed. Personalized medicine
      has the potential to have a significant impact on these issues, but for it to be
      truly successful, interdisciplinary mass collaboration is required. We propose
      here a vision for open-access advanced analytics for personalized cardiac
      diagnostics using imaging, electrocardiography and genomics. 

PMID- 25562655
TI  - Early inflammatory damage to intestinal neurons occurs via inducible nitric oxide
      synthase.
AB  - Intestinal inflammation affects the enteric nervous system (ENS) that lies
      adjacent to the smooth muscle layers. Previously, we showed that the loss of ENS
      neurons in animal models such as tri-nitrobenzene sulphonic acid (TNBS)-induced
      colitis was a limited and early event despite progressive worsening of
      inflammation. Here, we demonstrated that the rapid appearance of activated immune
      cells in the intestinal wall is selectively neurotoxic via iNOS-derived NO, using
      TNBS-induced colitis in both rats and mice, and a co-culture model of ENS neurons
      and smooth muscle. An influx of neutrophils and macrophages occurred within hours
      of initiation of rat colitis, correlating with iNOS expression, acutely elevated
      NO and neuronal death. In vitro, chemical donors of NO selectively caused axonal
      damage and neuronal death. These outcomes were similar to those seen with
      combined culture with either activated peritoneal immune cells or the immune cell
      lines RAW-264 and RBL-2H3. Immune cell-mediated neurotoxicity was blocked by the
      iNOS inhibitor L-NIL, and neuronal death was inhibited by the RIP-1 kinase
      inhibitor necrostatin. In a mouse model, the stereotypic loss of myenteric
      neurons by Day 4 post-TNBS was abrogated by the selective iNOS inhibitors L-NIL
      or 1400W without effect on other parameters of intestinal inflammation.
      Preservation of ENS neurons also ameliorated the hyperplasia of smooth muscle
      that is characteristic of intestinal inflammation, in line with prior work
      showing neural regulation of smooth muscle phenotype. This identifies a
      predominant pathway of immune cell damage to the ENS, where early, acute
      elevation of NO from iNOS can be cytotoxic to myenteric neurons.

PMID- 25562650
TI  - Antisense therapy in neurology.
AB  - Antisense therapy is an approach to fighting diseases using short DNA-like
      molecules called antisense oligonucleotides. Recently, antisense therapy has
      emerged as an exciting and promising strategy for the treatment of various
      neurodegenerative and neuromuscular disorders. Previous and ongoing pre-clinical
      and clinical trials have provided encouraging early results. Spinal muscular
      atrophy (SMA), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS),
      Duchenne muscular dystrophy (DMD), Fukuyama congenital muscular dystrophy (FCMD),
      dysferlinopathy (including limb-girdle muscular dystrophy 2B; LGMD2B, Miyoshi
      myopathy; MM, and distal myopathy with anterior tibial onset; DMAT), and myotonic
      dystrophy (DM) are all reported to be promising targets for antisense therapy.
      This paper focuses on the current progress of antisense therapies in neurology. 

PMID- 25562658
TI  - Indomethacin preconditioning induces ischemic tolerance by modifying zinc
      availability in the brain.
AB  - Intracellular zinc overload causes neuronal injury during the course of
      neurological disorders, whereas mild levels of zinc are beneficial to neurons.
      Previous reports indicated that non-steroidal anti-inflammatory drugs, including
      indomethacin and aspirin, can reduce the risk of ischemic stroke. This study
      found that chronic pretreatment of rats with indomethacin, a non-selective
      cyclooxygenase inhibitor, provided tolerance to ischemic injuries in an animal
      model of stroke by eliciting moderate zinc elevation in neurons. Consecutive
      intraperitoneal injection of indomethacin (3mg/kg/day for 28 days) led to modest
      increases in intraneuronal zinc as well as synaptic zinc content, with no
      significant stimulation of neuronal death. Furthermore, indomethacin induced the
      expressions of intracellular zinc homeostatic and neuroprotective proteins,
      rendering the brain resistant against ischemic damages and improving neurological
      outcomes. However, administration of a zinc-chelator, N,N,N',N'-tetra(2
      picolyl)ethylenediamine (TPEN; 15 mg/kg/day), immediately after indomethacin
      administration eliminated the beneficial actions of the drug. Therefore,
      indomethacin preconditioning can modulate intracellular zinc availability,
      contributing to ischemic tolerance in the brain after stroke.

PMID- 25562656
TI  - Modeling the natural history of Pelizaeus-Merzbacher disease.
AB  - Major gaps in our understanding of the leukodystrophies result from their rarity
      and the lack of tissue for the interdisciplinary studies required to extend our
      knowledge of the pathophysiology of the diseases. This study details the natural
      evolution of changes in the CNS of the shaking pup (shp), a model of the
      classical form of the X-linked disorder Pelizaeus-Merzbacher disease, in
      particular in glia, myelin, and axons, which is likely representative of what
      occurs over time in the human disease. The mutation in the proteolipid protein
      gene, PLP1, leads to a delay in differentiation, increased cell death, and a
      marked distension of the rough endoplasmic reticulum in oligodendrocytes.
      However, over time, more oligodendrocytes differentiate and survive in the spinal
      cord leading to an almost total recovery of myelination, In contrast, the brain
      remains persistently hypomyelinated. These data suggest that shp oligodendrocytes
      may be more functional than previously realized and that their early recruitment
      could have therapeutic value. 

PMID- 25562657
TI  - Homeostatic regulation of KCC2 activity by the zinc receptor mZnR/GPR39 during
      seizures.
AB  - The aim of this study was to investigate the role of the synaptic metabotropic
      zinc receptor mZnR/GPR39 in physiological adaptation to epileptic seizures. We
      previously demonstrated that synaptic activation of mZnR/GPR39 enhances
      inhibitory drive in the hippocampus by upregulating neuronal K(+)/Cl(-) co
      transporter 2 (KCC2) activity. Here, we first show that mZnR/GPR39 knockout (KO)
      adult mice have dramatically enhanced susceptibility to seizures triggered by a
      single intraperitoneal injection of kainic acid, when compared to wild type (WT)
      littermates. Kainate also substantially enhances seizure-associated gamma
      oscillatory activity in juvenile mZnR/GPR39 KO hippocampal slices, a phenomenon
      that can be reproduced in WT tissue by extracellular Zn(2+) chelation.
      Importantly, kainate-induced synaptic Zn(2+) release enhances surface expression
      and transport activity of KCC2 in WT, but not mZnR/GPR39 KO hippocampal neurons.
      Kainate-dependent upregulation of KCC2 requires mZnR/GPR39 activation of the
      Galphaq/phospholipase C/extracellular regulated kinase (ERK1/2) signaling
      cascade. We suggest that mZnR/GPR39-dependent upregulation of KCC2 activity
      provides homeostatic adaptation to an excitotoxic stimulus by increasing
      inhibition. As such, mZnR/GPR39 may provide a novel pharmacological target for
      dampening epileptic seizure activity. 

PMID- 25562659
TI  - Fragile X mice have robust mGluR5-dependent alterations of social behaviour in
      the Automated Tube Test.
AB  - Fragile X syndrome is the most common monogenetic form of intellectual disability
      and autism. Although the Fmr1 knockout mouse model recapitulates many aspects of
      the human FXS condition, the establishment of robust social behavioural
      phenotypes suitable for drug screening has been difficult. Here, we describe a
      novel social behavioural paradigm, the Automated Tube Test (ATT), for which Fmr1
      knockout mice demonstrate a highly reliable and robust phenotype. Fmr1 KO mice
      show highly dominant behaviour over wild-type littermates in the ATT. Consistent
      with previous findings, we observed a highly significant, albeit partial, rescue
      of the altered social behaviour of Fmr1 knockout mice in the ATT, using genetic
      (mGluR5 deletion) or pharmacological inhibition (mGluR5 antagonist) of mGluR5
      signalling independently. Together, our results validate the Automated Tube Test
      as a robust outcome measure for social behaviour in preclinical research for FXS,
      and confirm the pathophysiological relevance of mGluR5 signalling. Moreover, our
      findings highlight the strategy of initiating pharmacological intervention in
      adulthood as holding significant clinical potential. 

PMID- 25562661
TI  - Three-dimensional analysis of a lofted instep kick by male and female
      footballers.
AB  - There is a paucity of data describing the lofted instep kick and little
      information on the kinematic differences between male and female footballers.
      This study provides a preliminary investigation into the differences in motion
      patterns between the sexes. A four-camera motion analysis system videoed 13
      amateur footballers (7 female and 6 male) attempting a standardised task that
      represented a lofted instep kick of approximately 35 m. Footballers performed 20
      kicks, with the three trials categorised closest to the standardised distance
      retained for statistical analysis. Three-dimensional motion patterns for kicks of
      35 m illustrated that female footballers produced greater fluctuation in movement
      patterns for pelvic, hip joint and thoracolumbar spine motion in the frontal
      plane; thorax and hip joint transverse rotation; and ankle
      dorsiflexion/plantarflexion motion. Peak hip extension (P = 0.018), impact hip
      abduction (P = 0.032), impact ankle plantar flexion (P = 0.030) and resultant
      ball velocity (P = 0.004) differed significantly between sexes. Principle
      component analysis highlighted associations between kinematic variables related
      to ball velocity and sex including a reduced hip abduction and increased internal
      rotation approaching impact, and greater peak knee flexion, respectively. In
      summary, increased variation in direction of segment motion, increased backswing
      and formation of a tension arc by females compared to males, may be related to
      anthropometric, strength and muscle activation differences. Specifically, this
      exploratory study indicates future research would benefit from exploring trunk,
      pelvis and hip kinematics and kinetics, and whether training the trunk, pelvis
      and hip musculature assists female footballers. 

PMID- 25562660
TI  - Centromeric binding and activity of Protein Phosphatase 4.
AB  - The cell division cycle requires tight coupling between protein phosphorylation
      and dephosphorylation. However, understanding the cell cycle roles of multimeric
      protein phosphatases has been limited by the lack of knowledge of how their
      diverse regulatory subunits target highly conserved catalytic subunits to their
      sites of action. Phosphoprotein phosphatase 4 (PP4) has been recently shown to
      participate in the regulation of cell cycle progression. We now find that the
      EVH1 domain of the regulatory subunit 3 of Drosophila PP4, Falafel (Flfl),
      directly interacts with the centromeric protein C (CENP-C). Unlike other EVH1
      domains that interact with proline-rich ligands, the crystal structure of the
      Flfl amino-terminal EVH1 domain bound to a CENP-C peptide reveals a new target
      recognition mode for the phosphatase subunit. We also show that binding of Flfl
      to CENP-C is required to bring PP4 activity to centromeres to maintain CENP-C and
      attached core kinetochore proteins at chromosomes during mitosis. 

PMID- 25562662
TI  - Exploring the drug resistance of V32I and M46L mutant HIV-1 protease to inhibitor
      TMC114: flap dynamics and binding mechanism.
AB  - Inhibitors of HIV-1 protease (HIV-1-pr) generally only bind to the active site of
      the protease. However, for some mutants such as V32I and M46L the TMC114 can bind
      not only to the active cavity but also to the groove of the flexible flaps.
      Although the second binding site suggests the higher efficiency of the drug
      against HIV-1-pr, the drug resistance in HIV-1-pr due to mutations cannot be
      ignored, which prompts us to investigate the molecular mechanisms of drug
      resistance and behavior of double bound TMC114 (2T) to HIV-1-pr. The
      conformational dynamics of HIV-1-pr and the binding of TMC114 to the WT, V32I and
      M46L mutants were investigated with all-atom molecular dynamic (MD) simulation.
      The 20 ns MD simulation shows many fascinating effects of the inhibitor binding
      to the WT and mutant proteases. MM-PBSA calculations explain the binding free
      energies unfavorable for the M46L and V32I mutants as compared to the WT. For the
      single binding (1T) the less binding affinity can be attributed to the entropic
      loss for both V32I-1T and M46L-1T. Although the second binding of TMC114 with
      flap does increase binding energy for the mutants (V32I-2T and M46L-2T), the
      considerable entropy loss results in the lower binding Gibbs free energies. Thus,
      binding of TMC114 in the flap region does not help much in the total gain in
      binding affinity of the system, which was verified from this study and thereby
      validating experiments.

PMID- 25562665
TI  - 3D ToF-SIMS imaging of polymer multilayer films using argon cluster sputter depth
      profiling.
AB  - ToF-SIMS imaging with argon cluster sputter depth profiling has provided detailed
      insight into the three-dimensional (3D) chemical composition of a series of
      polymer multilayer structures. Depths of more than 15 MUm were profiled in these
      samples while maintaining uniform sputter rates. The 3D chemical images provide
      information regarding the structure of the multilayer systems that could be used
      to inform future systems manufacturing and development. This also includes
      measuring the layer homogeneity, thickness, and interface widths. The systems
      analyzed were spin-cast multilayers comprising alternating polystyrene (PS) and
      polyvinylpyrrolidone (PVP) layers. These included samples where the PVP and PS
      layer thickness values were kept constant throughout and samples where the layer
      thickness was varied as a function of depth in the multilayer. The depth profile
      data obtained was observed to be superior to that obtained for the same materials
      using alternative ion sources such as C60(n+). The data closely reflected the "as
      manufactured" sample specification, exhibiting good agreement with ellipsometry
      measurements of layer thickness, while also maintaining secondary ion intensities
      throughout the profiling regime. The unprecedented quality of the data allowed a
      detailed analysis of the chemical structure of these systems, revealing some
      minor imperfections within the polymer layers and demonstrating the enhanced
      capabilities of the argon cluster depth profiling technique. 

PMID- 25562663
TI  - DFT studies of the formation of furanoid derivatives of ammonium chlorides.
AB  - B3LYP/6-31+G** level computations were performed on the formation of ammonium
      salts during the reaction of (S)-1,4-anhydro-5-chloro-2,3,5-trideoxypentitol (1)
      (2S,5S)-2,5-anhydro-6-chloro-1,3,4,6-tetradeoxyhexitol (2) and methyl 5-chloro
      2,3,5-trideoxy-beta-D-pentofuranoside (3) with ammonia in order to describe the
      reaction pathway in detail. All the structures were fully optimized in the gas
      phase, in chloroform and water. In addition, the gas phase activation barrier
      heights were estimated at B3LYP/6-311++G**, MPWIK/6-31+G**, MPWIK/6-311++G** and
      MP2/6-311++G(2d,2p)//MPWIK/6-31+G** levels of theory. All the calculations in
      solvents were performed the using polarizable continuum model (PCM) and the B3LYP
      functional with the 6-31+G** basis set. A detailed description of all the
      stationary points is presented, and the conformational behavior of the five
      membered ring is discussed in the gas phase and in the solvents. The conversion
      of the reactant complexes into ion pairs is accompanied by a strong energy
      decrease in the gas phase and in all the solvents. The overall process is
      strongly unfavorable in the gas phase, but takes place readily in high-polarity
      solvents. 

PMID- 25562664
TI  - Depsipeptide companeramides from a Panamanian marine cyanobacterium associated
      with the coibamide producer.
AB  - Two new cyclic depsipeptides, companeramides A (1) and B (2), have been isolated
      from the phylogenetically characterized cyanobacterial collection that yielded
      the previously reported cancer cell toxin coibamide A (collected from Coiba
      Island, Panama). The planar structures of the companeramides, which contain 3
      amino-2-methyl-7-octynoic acid (Amoya), hydroxy isovaleric acid (Hiva), and eight
      alpha-amino acid units, were established by NMR spectroscopy and mass
      spectrometry. The absolute configuration of each companeramide was assigned using
      a combination of Marfey's methodology and chiral-phase HPLC analysis of complete
      and partial hydrolysis products compared to commercial and synthesized standards.
      Companeramides A (1) and B (2) showed high nanomolar in vitro antiplasmodial
      activity but were not overtly cytotoxic to four human cancer cell lines at the
      doses tested.

PMID- 25562666
TI  - Caspase-1 activity is required for UVB-induced apoptosis of human keratinocytes.
AB  - Caspase-1 has a crucial role in innate immunity as the protease activates the
      proinflammatory cytokine prointerleukin(IL)-1beta. Furthermore, caspase-1 induces
      pyroptosis, a lytic form of cell death that supports inflammation. Activation of
      caspase-1 occurs in multi-protein complexes termed inflammasomes, which assemble
      upon sensing of stress signals. In the skin and in skin-derived keratinocytes,
      UVB irradiation induces inflammasome-dependent IL-1 secretion and sunburn. Here
      we present evidence that caspase-1 and caspase-4 are required for UVB-induced
      apoptosis. In UVB-irradiated human primary keratinocytes, apoptosis occurs
      significantly later than inflammasome activation but depends on caspase-1
      activity. However, it proceeds independently of inflammasome activation. By a
      proteomics approach, we identified the antiapoptotic Bap31 as a putative caspase
      1 substrate. Caspase-1-dependent apoptosis is possibly a recent process in
      evolution as it was not detected in mice. These results suggest a protective role
      of caspase-1 in keratinocytes during UVB-induced skin cancer development through
      the induction of apoptosis. 

PMID- 25562667
TI  - eIF4E is an adverse prognostic marker of melanoma patient survival by increasing
      melanoma cell invasion.
AB  - Human cutaneous melanoma is a devastating skin cancer because of its invasive
      nature and high metastatic potential. We used tissue microarray to study the role
      of human eukaryotic translation initiation factor 4E (eIF4E) in melanoma
      progression in 448 melanocytic lesions and found that high eIF4E expression was
      significantly increased in primary melanomas compared with dysplastic nevi
      (P<0.001), and further increased in metastatic melanomas (P<0.001). High eIF4E
      expression was associated with melanoma thickness (P=0.046), and poor overall and
      disease-specific 5-year survival of all, and primary melanoma patients,
      especially those with tumors >=1 mm thick. Multivariate Cox regression analysis
      revealed that eIF4E is an independent prognostic marker. eIF4E knockdown (KD) in
      melanoma cells resulted in a significant increase in apoptosis (sub-G1
      populations) and decrease in cell proliferation, and also resulted in
      downregulation of mesenchymal markers and upregulation of E-cadherin. In
      addition, eIF4E KD led to a decrease in melanoma cell invasion, matrix
      metalloproteinase-2 expression and activity, c-myc and BCL2 expression, and an
      increase in cleaved PARP and cleaved caspase-3 expression and chemosensitivity.
      Taken together, our data suggest that the eIF4E may promote melanoma cell
      invasion and metastasis, and may also serve as a promising prognostic marker and
      a potential therapeutic target for melanoma. 

PMID- 25562668
TI  - Toxicity and cost-effectiveness analysis of intensity modulated radiation therapy
      versus 3-dimensional conformal radiation therapy for postoperative treatment of
      gynecologic cancers.
AB  - OBJECTIVE: To evaluate toxicity and cost-effectiveness of intensity modulated
      radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT)
      in the postoperative treatment of uterine and cervical cancer. METHODS: Between
      2000 and 2012, eighty patients at our institution received post-hysterectomy
      3DCRT (46) or IMRT (34) for uterine or cervical cancer. Baseline characteristics,
      outcome, and >=CTCAE grade 2 toxicities were compared between the two groups.
      Predictors of toxicity-free survival were identified. A decision analysis model
      was designed to capture individual health states at 1, 2, and 3 years after
      treatment. Micro-costing technique and estimated quality-adjusted life years
      (QALYs) were used to calculate incremental cost-effectiveness ratio (ICER).
      RESULTS: Utilization of IMRT increased from 25% (2005-2007) to 75% (2008-2012).
      Recurrence-free and overall survival rates were not different between the two
      groups. Toxicity rates were reduced with IMRT versus 3DCRT (HR 0.42, p=0.04).
      Women who received IMRT had numerically lower rates of late gastrointestinal and
      genitourinary toxicity and significantly lower rates of late overall toxicity at
      3 years (16% vs. 45%, p=0.04). On univariate analysis, IMRT was associated with
      decreased late toxicity (HR 0.43, p=0.04). Treatment costs were higher and
      toxicity costs were lower with IMRT. IMRT had an ICER of $235,233 (year 1),
      $114,270 (year 2), and $75,555 (year 3) per QALY gained. CONCLUSION: IMRT is
      associated with reduced late overall toxicity compared to 3DCRT without
      compromising clinical outcome. IMRT is not cost-effective during the early
      chronic toxicity phase, but it becomes more cost-effective over time.

PMID- 25562669
TI  - Uranium(VI) Binding Forms in Selected Human Body Fluids:  Thermodynamic
      Calculations versus Spectroscopic Measurements.
AB  - Human exposure to uranium increasingly becomes a subject of interest in many
      scientific disciplines such as environmental medicine, toxicology, and radiation
      protection. Knowledge about uranium chemical binding forms(speciation) in human
      body fluids can be of great importance to understand not only its biokinetics but
      also its relevance in risk assessment and in designing decorporation therapy in
      the case of accidental overexposure. In this study, thermodynamic calculations of
      uranium speciation in relevant simulated and original body fluids were compared
      with spectroscopic data after ex-situ uranium addition. For the first time,
      experimental data on U(VI) speciation in body fluids (saliva, sweat, urine) was
      obtained by means of cryogenic time-resolved laser-induced fluorescence
      spectroscopy (cryo-TRLFS) at 153 K. By using the time dependency of fluorescence
      decay and the band positions of the emission spectra, various uranyl complexes
      were demonstrated in the studied samples. The variations of the body fluids in
      terms of chemical composition, pH, and ionic strength resulted in different
      binding forms of U(VI). The speciation of U(VI) in saliva and in urine was
      affected by the presence of bioorganic ligands, whereas in sweat, the
      distribution depends mainly on inorganic ligands. We also elucidated the role of
      biological buffers, i.e., phosphate (H(2)PO(4-)/HPO(4)(2-)) on U(VI)
      distribution, and the system Ca(2+)/UO(2)(2+)/PO(4)(3-) was discussed in detail
      in both saliva and urine. The theoretical speciation calculations of the main
      U(VI) species in the investigated body fluids were significantly consistent with
      the spectroscopic data. Laser fluorescence spectroscopy showed success and
      reliability for direct determination of U(VI) in such biological matrices with
      the possibility for further improvement.

PMID- 25562670
TI  - The role of adverse life events on depression in older adults with ADHD.
AB  - BACKGROUND: Comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD)
      and depression is high, also in older adults. Thus far it is not well understood
      why ADHD and depression are so strongly interrelated. One factor that may play a
      role in older adults with ADHD is an increased risk of experiencing adverse life
      events. METHODS: Six year follow-up data were used from the Longitudinal Aging
      Study Amsterdam (LASA). To diagnose ADHD, the DIVA 2.0, a diagnostic interview
      was administered among a subsample (N=230, age 60-94). In addition to the ADHD
      diagnosis, the associations between the number of ADHD symptoms, depressive
      symptoms and adverse life events were examined. Data were analyzed by means of
      logistic and linear regression analyses. RESULTS: Compared to older adults
      without ADHD, those with ADHD reported more serious conflicts. The risk of
      depression in older adults with ADHD was partly explained by serious conflicts.
      Furthermore, the association between ADHD severity and depression was stronger in
      those who experienced serious conflicts and those who experienced more adverse
      life events. LIMITATIONS: The ADHD diagnosis was based on the DSM-IV criteria,
      which were developed for children, and have not yet been validated in (older)
      adults. CONCLUSIONS: Having conflicts with others and accumulation of adverse
      life events over time partly explained the association between ADHD and
      depression. Better and earlier treatment of ADHD may prevent the development of
      depression in the presence of life events associated with ADHD.

PMID- 25562671
TI  - Test-retest reliability of a new questionnaire for the retrospective assessment
      of long-term lithium use in bipolar disorder.
AB  - BACKGROUND: The identification of predictors of treatment response holds
      tremendous potential for the improvement of clinical outcomes in bipolar disorder
      (BP). The goal of this project is to evaluate the test-retest reliability of a
      new clinical tool, the Lithium Questionnaire (LQ), for the retrospective
      assessment of long-term lithium use in research participants with BP. METHODS:
      Twenty-nine individuals with BP-I (n=27), major depression (n=1), or
      schizoaffective disorder (n=1) were recruited for participation. The LQ was
      administered to all participants at two time-points, spaced 17 months apart on
      average, and used to determine each subject's score on the Retrospective Criteria
      of Long-Term Treatment Response in Research Subjects with Bipolar Disorder Scale,
      or the Alda Scale. Scores were confirmed through a best-estimate procedure, and
      test-retest reliability (intra-class correlation coefficient [ICC]) of the LQ was
      calculated. RESULTS: The correlation between the total Alda Scale scores at the
      two time-points was in the moderate range (ICC=0.60). Relevant clinical factors
      such as age or presence of Axis I psychiatric comorbidity did not influence the
      reliability. LIMITATIONS: The validity of the LQ was not examined. Inclusion of
      two participants with non-BP diagnoses may have affected the LQ's reliability,
      but re-analysis of our data after exclusion of these participants did not
      influence the reliability. The absence of measures of mood and cognition at time
      of LQ may be a limitation of this work. CONCLUSIONS: The LQ holds promise for the
      standardization of the retrospective assessment of long-term treatment in BP.

PMID- 25562673
TI  - Polymorphisms and functional haplotype in PADI4: further evidence for
      contribution on rheumatoid arthritis susceptibility and anti-cyclic citrullinated
      peptide antibodies in a western Mexican population.
AB  - Peptidyl arginine deiminase IV (PADI4) enzyme catalyzes the citrullination of
      proteins, which are recognized by anti-cyclic citrullinated peptide antibodies
      (anti-CCP) in rheumatoid arthritis (RA) patients. Here, we determined the
      association between PADI4 gene polymorphisms and haplotypes with RA
      susceptibility and clinical characteristics in a western Mexican population. The
      relationship of PADI4 polymorphisms with anti-CCP and PADI4 mRNA expression was
      also evaluated. PADI4_89, PADI4_90 and PADI4_92 polymorphisms were individually
      associated with RA susceptibility. The GTG haplotype was significantly associated
      with: RA susceptibility; disease onset at <= 40 years and anti-CCP antibodies.
      PADI4 expression was three fold higher in RA patients carrying the susceptibility
      haplotype (GTG) than in non-susceptibility haplotype carriers (ACC). In
      conclusion, polymorphisms and functional haplotype (GTG) in PADI4 are associated
      with RA susceptibility as well as anti-CCP antibodies in a Mexican population.
      This supports the role of PADI4 early in RA pathogenesis by promoting the
      generation of citrullinated autoantigens.

PMID- 25562674
TI  - Airway Epithelial Cell Integrity Protects from Cytotoxicity of Pseudomonas
      aeruginosa Quorum-Sensing Signals.
AB  - Cell-to-cell communication via gap junctions regulates airway epithelial cell
      homeostasis and maintains the epithelium host defense. Quorum-sensing molecules
      produced by Pseudomonas aeruginosa coordinate the expression of virulence factors
      by this respiratory pathogen. These bacterial signals may also incidentally
      modulate mammalian airway epithelial cell responses to the pathogen, a process
      called interkingdom signaling. We investigated the interactions between the P.
      aeruginosa N-3-oxo-dodecanoyl-L-homoserine lactone (C12) quorum-sensing molecule
      and human airway epithelial cell gap junctional intercellular communication
      (GJIC). C12 degradation and its effects on cells were monitored in various airway
      epithelial cell models grown under nonpolarized and polarized conditions. Its
      concentration was further monitored in daily tracheal aspirates of colonized
      intubated patients. C12 rapidly altered epithelial integrity and decreased GJIC
      in nonpolarized airway epithelial cells, whereas other quorum-sensing molecules
      had no effect. The effects of C12 were dependent on [Ca(2+)]i and could be
      prevented by inhibitors of Src tyrosine family and Rho-associated protein
      kinases. In contrast, polarized airway cells grown on Transwell filters were
      protected from C12 except when undergoing repair after wounding. In vivo during
      colonization of intubated patients, C12 did not accumulate, but it paralleled
      bacterial densities. In vitro C12 degradation, a reaction catalyzed by
      intracellular paraoxonase 2 (PON2), was impaired in nonpolarized cells, whereas
      PON2 expression was increased during epithelial polarization. The cytotoxicity of
      C12 on nonpolarized epithelial cells, combined with its impaired degradation
      allowing its accumulation, provides an additional pathogenic mechanism for P.
      aeruginosa infections. 

PMID- 25562675
TI  - Layer-by-layer assembled carbon nanotube-acetylcholinesterase/biopolymer
      renewable interfaces: SPR and electrochemical characterization.
AB  - Developing simple, reliable, and cost-effective methods of renewing an inhibited
      biocatalyst (e.g., enzymatic interfaces) on biosensors is needed to advance
      multiuse, reusable sensor applications. We report a method for the renewal of
      layer-by-layer (LbL) self-assembled inhibition-based enzymatic interfaces in
      multiwalled carbon nanotube (MWCNT) armored acetylcholinesterase (AChE)
      biosensors. The self-assembly process of MWCNT dispersed enzymes/biopolymers was
      investigated using surface plasmon resonance (SPR). The LbL fabrication consisted
      of alternating cushion layers of positively charged CNT-polyethylenimine (CNT
      PEI) and negatively charged CNT-deoxyribonucleic acid (CNT-DNA) and a functional
      interface consisting of alternating layers of CNT-PEI and negatively charged CNT
      acetylcholine esterase (CNT-AChE, pH 7.4). The observed SPR response signal
      increased while assembling the different layers, indicating the buildup of
      multiple layers on the Au surface. A partial desorption of the top enzymatic
      layer in the LbL structure was observed with a desorption strategy employing
      alkaline treatment. This indicates that the strong interaction of CNT-biopolymer
      conjugates with the Au surface was a result of both electrostatic interactions
      between biopolymers and the surface binding energy from CNTs: the closer the
      layers are to the Au surface, the stronger the interactions. In contrast, a
      similar LbL assembly of soluble enzyme/polyelectrolytes resulted in stronger
      desorption on the surface after the alkaline treatment; this led to the
      investigation of AChE layer removal, permanently inhibited after pesticide
      exposure on glassy carbon (GC) electrodes, while keeping the cushion layers
      intact. The desorption strategy permitted the SPR and electrochemical electrode
      surfaces to be regenerated multiple times by the subsequent self-assembly of
      fresh PEI/AChE layers. Flow-mode electrochemical amperometric analysis
      demonstrated good stability toward the determination of acetylcholine with 97.1
      +/- 2.7% renewability. Our simple, inexpensive approach shows the potential of
      renewable LbL self-assembled functional interfaces for multiple uses in a wide
      field of applications such as biosensing, various biotechnological processes, and
      the food and health industries. 

PMID- 25562676
TI  - The common genetic variant rs944289 on chromosome 14q13.3 associates with risk of
      both malignant and benign thyroid tumors in the Japanese population.
AB  - BACKGROUND: Several single nucleotide polymorphisms (SNP) have been identified to
      be associated with the risk for differentiated thyroid cancer in populations of
      distinct ethnic background. The relationship of these genetic markers to a benign
      tumor of the thyroid, follicular adenoma (FA), is not well established. METHODS:
      In a multicenter retrospective case-control study, five thyroid cancer-related
      SNPs-rs966513 (9q22.33, FOXE1), rs944289 (14q13.3, PTCSC3), rs2439302 (8p12,
      NRG1), rs1867277 (9q22.23, FOXE1), and rs6983267 (8q24, POU5F1B)-were genotyped
      in 959 cases of histologically verified FA, 535 papillary thyroid carcinomas
      (PTC), and 2766 population controls. RESULTS: A significant association was found
      between FA and rs944289 (p=0.002; OR 1.176 [CI 1.064-1.316]), and suggestively
      with rs2439302 (p=0.033; OR 1.149 [CI 1.010-1.315]). In PTC, significant
      associations were confirmed for rs965513 (p=4.21E-04; OR 1.587 [CI 1.235-2.000])
      and rs944289 (p=0.003; OR 1.234 [CI 1.075-1.408]), newly found for rs2439302
      (p=0.003; OR 1.266 [CI 1.087-1.493]) and rs1867277 (p=1.17E-04; OR 1.492 [CI
      1.235-1.818]), and was not replicated for rs6983267 (p=0.082; OR 1.136 [CI 0.980
      1.316]) in this series. A significant correlation between rs2439302 genotype and
      relative expression of NRG1 was detected in normal and tumor counterparts of PTC
      (about 10% decrease per each risk allele). NRG1 expression also significantly
      correlated with that of PTCSC3. CONCLUSIONS: Association of rs944289, which was
      previously known to confer risk for thyroid cancer, with FA, and the correlation
      between PTCSC3 and NRG1 expression demonstrates that predisposing genetic factors
      are partly common for benign and malignant thyroid tumors, and imply broader
      roles of the pathways they underlie in thyroid tumorigenesis, not limited to
      carcinogenesis.

PMID- 25562677
TI  - Simulation, design, and testing of a high power collimator for the RDS-112
      cyclotron.
AB  - A high power [F-18] fluoride target package for the RDS-112 cyclotron has been
      designed, tested, and commercially deployed. The upgrade includes the CF-1000
      target, a 1.3kW water target with an established commercial history on RDS
      111/Eclipse cyclotrons, and a redesigned collimator with improved heat rejection
      capabilities. Conjugate heat transfer analyses were employed to both evaluate the
      existing collimator capabilities and design a suitable high current replacement. 

PMID- 25562678
TI  - Experimental dosimetry in conformal breast teletherapy compared with the planning
      system.
AB  - The objective of this study was to compare and analyse the absorbed dose profiles
      from the conformal radiotherapy planning and experimental dosimetry taken in a
      breast anthropomorphic and anthropometric phantom. Conformal radiotherapy
      planning was elaborated in the Treatment Planning System (TPS). EBT2 Gafchromic
      radiochromic films were applied as dosimeters, positioned internally and
      superficially in the breast phantom. The standard radiation protocol was applied
      in the breast phantom. The films were digitalised, and their responses were
      analysed in RGB. The optical densities were processed, reproducing the spatial
      dose distribution. 

PMID- 25562679
TI  - Microdosimetry spectra and relative biological effectiveness of 15 and 30MeV
      proton beams.
AB  - The relative biological effectiveness (RBE) of high-energy protons has been well
      investigated, but estimates of RBE for lower-energy (<40MeV) protons are scarce.
      In the present work, measurements were made of the lineal energy spectra using a
      home-made miniature tissue-equivalent proportional counter for 15 and 30MeV
      protons from the TR 30/15 cyclotron. Monte Carlo simulations were made for the
      same spectra using the FLUKA code. These spectra were coupled to several
      biological models to evaluate the RBE for various biological endpoints. 

PMID- 25562672
TI  - Seasonality shows evidence for polygenic architecture and genetic correlation
      with schizophrenia and bipolar disorder.
AB  - OBJECTIVE: To test common genetic variants for association with seasonality
      (seasonal changes in mood and behavior) and to investigate whether there are
      shared genetic risk factors between psychiatric disorders and seasonality.
      METHOD: Genome-wide association studies (GWASs) were conducted in Australian
      (between 1988 and 1990 and between 2010 and 2013) and Amish (between May 2010 and
      December 2011) samples in whom the Seasonal Pattern Assessment Questionnaire
      (SPAQ) had been administered, and the results were meta-analyzed in a total
      sample of 4,156 individuals. Genetic risk scores based on results from prior
      large GWAS studies of bipolar disorder, major depressive disorder (MDD), and
      schizophrenia were calculated to test for overlap in risk between psychiatric
      disorders and seasonality. RESULTS: The most significant association was with
      rs11825064 (P = 1.7 * 10-6, beta = 0.64, standard error = 0.13), an intergenic
      single nucleotide polymorphism (SNP) found on chromosome 11. The evidence for
      overlap in risk factors was strongest for schizophrenia and seasonality, with the
      schizophrenia genetic profile scores explaining 3% of the variance in log
      transformed global seasonality scores. Bipolar disorder genetic profile scores
      were also associated with seasonality, although at much weaker levels (minimum P
      value = 3.4 * 10-3), and no evidence for overlap in risk was detected between MDD
      and seasonality. CONCLUSIONS: Common SNPs of large effect most likely do not
      exist for seasonality in the populations examined. As expected, there were
      overlapping genetic risk factors for bipolar disorder (but not MDD) with
      seasonality. Unexpectedly, the risk for schizophrenia and seasonality had the
      largest overlap, an unprecedented finding that requires replication in other
      populations and has potential clinical implications considering overlapping
      cognitive deficits in seasonal affective disorders and schizophrenia.

PMID- 25562680
TI  - Tumor-to-tumor metastasis of breast carcinoma to cervical spinal schwannoma: Case
      report.
AB  - Tumor-to-tumor metastasis with schwannoma as a recipient tumor is very rare.
      There have been no reports on tumor to spinal schwannoma metastasis. We report a
      case of a 57-year-old woman who presented with neck pain and who turned out to
      have cervical spinal nerve schwannoma with breast carcinoma metastasis. 

PMID- 25562681
TI  - Thermal injury of thoracic spinal cord after percutaneous cryoablation of spinal
      tumor--When needles are more dangerous than the knife.

PMID- 25562682
TI  - Mixed capillary-cavernous extramedullary intradural hemangioma of the spinal cord
      mimicking meningioma: Case report.
AB  - Hemangiomas are customarily described as low-grade vascular tumors most often
      located in the head and neck, but on rare occasions occurring in the intradural
      space of the spine. The different subtypes of hemangiomas can be distinguished
      histologically as capillary, cavernous, or mixed types. We describe a rare case
      of a mixed capillary-cavernous extramedullary intradural hemangioma of the
      thoracic spinal cord, mimicking meningioma radiologically. 

PMID- 25562683
TI  - Electrophile-integrating Smiles rearrangement provides previously inaccessible
      C4'-O-alkyl heptamethine cyanine fluorophores.
AB  - New synthetic methods to rapidly access useful fluorophores are needed to advance
      modern molecular imaging techniques. A new variant of the classical Smiles
      rearrangement is reported that enables the efficient synthesis of previously
      inaccessible C4'-O-alkyl heptamethine cyanines. The key reaction involves N- to O
      transposition with selective electrophile incorporation on nitrogen. A
      representative fluorophore exhibits excellent resistance to thiol nucleophiles,
      undergoes productive bioconjugation, and can be used in near-IR fluorescence
      imaging applications.

PMID- 25562684
TI  - Prenatally administered dexamethasone impairs folliculogenesis in spiny mouse
      offspring.
AB  - This study was designed to determine whether prenatal dexamethasone treatment has
      an effect on follicular development and atresia in the ovary of spiny mouse
      (Acomys cahirinus) offspring. Dexamethasone (125ug kg-1 bodyweight per day) was
      administered to pregnant spiny mice from Day 20 of gestation to parturition. The
      processes of follicle loss were analysed using classical markers of apoptosis
      (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling reaction,
      active caspase-3) and autophagy (Lamp1). The present study indicated that
      dexamethasone reduced the pool of healthy primordial follicles. Moreover, the
      oocytes from these follicles showed intensive caspase-3 and Lamp1 staining.
      Surprisingly, dexamethasone caused an increase in the number of secondary
      follicles; however, most of these follicles were characterised by extensive
      degeneration of the oocyte and caspase-3 and Lamp1 labelling. Western-blot
      analysis indicated that the glucocorticoid receptor as well as apoptosis and
      autophagy markers were more strongly expressed in the DEX-treated group than in
      the control. On the basis of these findings, we have concluded that dexamethasone
      impairs spiny mouse folliculogenesis and enhances follicular atresia through
      induction of autophagy or combined autophagy and apoptosis.

PMID- 25562685
TI  - Paliperidone palmitate once-monthly reduces risk of relapse of psychotic,
      depressive, and manic symptoms and maintains functioning in a double-blind,
      randomized study of schizoaffective disorder.
AB  - OBJECTIVE: Schizoaffective disorder is a complex illness for which optimal
      treatment is not well established. Results of the first controlled, relapse
      prevention study of paliperidone palmitate once-monthly injectable (paliperidone
      monthly) in schizoaffective disorder are presented. METHOD: The study was
      conducted between September 20, 2010, and October 22, 2013. Patients with
      schizoaffective disorder (confirmed by the Structured Clinical Interview for DSM
      IV Axis I Disorders) experiencing acute exacerbation of psychotic and
      depressive/manic symptoms were stabilized with paliperidone monthly as
      monotherapy or as adjunctive therapy to mood stabilizers or antidepressants and
      randomly assigned (1:1) to paliperidone monthly or placebo in a 15-month, double
      blind, relapse-prevention phase. Randomization was stratified by administration
      as monotherapy or adjunctive therapy and by study center. The primary endpoint
      was time to relapse. RESULTS: 334 patients were evaluated. Paliperidone monthly
      significantly delayed time to relapse for psychotic, depressive, and manic
      symptoms compared with placebo (P < .001, log-rank test). Relapse risk was 2.49
      times greater for placebo (hazard ratio = 2.49; 95% CI, 1.55 to 3.99; P < .001,
      Cox proportional hazards model). Overall relapse rates were 33.5% for placebo and
      15.2% for paliperidone monthly. For monotherapy, relapse risk was 3.38 times
      greater with placebo (P = .002), and for adjunctive treatment it was 2.03 times
      greater with placebo (P = .021). Paliperidone monthly was superior to placebo in
      maintaining functioning as measured by the Personal and Social Performance scale
      (P = .014, mixed-model repeated-measures analysis). The most common adverse
      events (placebo, paliperidone monthly) were increased weight (4.7%, 8.5%),
      insomnia (7.1%, 4.9%), schizoaffective disorder (5.9%, 3.0%), headache (3.5%,
      5.5%), and nasopharyngitis (3.5%, 5.5%). Incidence of any extrapyramidal-related
      adverse event was 7.1% for placebo and 8.5% for paliperidone monthly.
      CONCLUSIONS: Paliperidone monthly as monotherapy or adjunctive therapy
      significantly delayed psychotic, depressive, and/or manic relapses; reduced their
      risk; and better maintained functioning in patients with schizoaffective
      disorder. Results support the value of maintenance treatment with paliperidone
      monthly in schizoaffective disorder. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT01193153.

PMID- 25562687
TI  - Electron collection in host-guest nanostructured hematite photoanodes for water
      splitting: the influence of scaffold doping density.
AB  - Nanostructuring has proven to be a successful strategy in overcoming the trade
      off between light absorption and hole transport to the solid/electrolyte
      interface in hematite photoanodes for water splitting. The suggestion that poor
      electron (majority carrier) collection hinders the performance of nanostructured
      hematite electrodes has led to the emergence of host-guest architectures in which
      the absorber layer is deposited onto a transparent high-surface-area electron
      collector. To date, however, state of the art nanostructured hematite electrodes
      still outperform their host-guest counterparts, and a quantitative evaluation of
      the benefits of the host-guest architecture is still lacking. In this paper, we
      examine the impact of host-guest architectures by comparing nanostructured tin
      doped hematite electrodes with hematite nanoparticle layers coated onto two types
      of conducting macroporous SnO2 scaffolds. Analysis of the external quantum
      efficiency spectra for substrate (SI) and electrolyte side (EI) illumination
      reveals that the electron diffusion length in the host-guest electrodes based on
      an undoped SnO2 scaffold is increased substantially relative to the
      nanostructured hematite electrode without a supporting scaffold. Nevertheless,
      electron collection is still incomplete for EI illumination. By contrast, an
      electron collection efficiency of 100% is achieved by fabricating the scaffold
      using antimony-doped SnO2, showing that the scaffold conductivity is crucial for
      the device performance. 

PMID- 25562686
TI  - The selective activation of p53 target genes regulated by SMYD2 in BIX-01294
      induced autophagy-related cell death.
AB  - Transcription regulation emerged to be one of the key mechanisms in regulating
      autophagy. Inhibitors of H3K9 methylation activates the expression of LC3B, as
      well as other autophagy-related genes, and promotes autophagy process. However,
      the detailed mechanisms of autophagy regulated by nuclear factors remain elusive.
      In this study, we performed a drug screen of SMYD2-/- cells and discovered that
      SMYD2 deficiency enhanced the cell death induced by BIX01294, an inhibitor of
      histone H3K9 methylation. BIX-01294 induces accumulation of LC3 II and autophagy
      related cell death, but not caspase-dependent apoptosis. We profiled the global
      gene expression pattern after treatment with BIX-01294, in comparison with
      rapamycin. BIX-01294 selectively activates the downstream genes of p53 signaling,
      such as p21 and DOR, but not PUMA, a typical p53 target gene inducing apoptosis.
      BIX-01294 also induces other autophagy-related genes, such as ATG4A and ATG9A.
      SMYD2 is a methyltransferase for p53 and regulates its transcription activity.
      Its deficiency enhances the BIX-01294-induced autophagy-related cell death
      through transcriptionally promoting the expression of p53 target genes. Taken
      together, our data suggest BIX-01294 induces autophagy-related cell death and
      selectively activates p53 target genes, which is repressed by SMYD2
      methyltransferase. 

PMID- 25562689
TI  - Effect of swim speed on leg-to-arm coordination in unilateral arm amputee front
      crawl swimmers.
AB  - The aim of this study was to examine the effect of swimming speed on leg-to-arm
      coordination in competitive unilateral arm amputee front crawl swimmers. Thirteen
      well-trained swimmers were videotaped underwater during three 25-m front crawl
      trials (400 m, 100 m and 50 m pace). The number, duration and timing of leg kicks
      in relation to arm stroke phases were identified by video analysis. Within the
      group, a six-beat kick was predominantly used (n = 10) although some swimmers
      used a four-beat (n = 2) or eight-beat kick (n = 1). Swimming speed had no
      significant effect on the relative duration of arm stroke and leg kick phases. At
      all speeds, arm stroke phases were significantly different (P < 0.05) between the
      affected and unaffected sides. In contrast, the kicking phases of both legs were
      not different. Consequently, leg-to-arm coordination was asymmetrical. The
      instant when the leg kicks ended on the affected side corresponded with
      particular positions of the unaffected arm, but not with the same positions of
      the affected arm. In conclusion, the ability to dissociate the movements of the
      arms from the legs demonstrates that, because of their physical impairment,
      unilateral arm amputee swimmers functionally adapt their motor organisation to
      swim front crawl. 

PMID- 25562690
TI  - Composite fermions and broken symmetries in graphene.
AB  - The electronic properties of graphene are described by a Dirac Hamiltonian with a
      four-fold symmetry of spin and valley. This symmetry may yield novel fractional
      quantum Hall (FQH) states at high magnetic field depending on the relative
      strength of symmetry-breaking interactions. However, observing such states in
      transport remains challenging in graphene, as they are easily destroyed by
      disorder. In this work, we observe in the first two Landau levels the two-flux
      composite-fermion sequences of FQH states between each integer filling factor. In
      particular, the odd-numerator fractions appear between filling factors 1 and 2,
      suggesting a broken-valley symmetry, consistent with our observation of a gap at
      charge neutrality and zero field. Contrary to our expectations, the evolution of
      gaps in a parallel magnetic field suggests that states in the first Landau level
      are not spin-polarized even up to very large out-of-plane fields. 

PMID- 25562688
TI  - Distinct brain systems mediate the effects of nociceptive input and self
      regulation on pain.
AB  - Cognitive self-regulation can strongly modulate pain and emotion. However, it is
      unclear whether self-regulation primarily influences primary nociceptive and
      affective processes or evaluative ones. In this study, participants engaged in
      self-regulation to increase or decrease pain while experiencing multiple levels
      of painful heat during functional magnetic resonance imaging (fMRI) imaging. Both
      heat intensity and self-regulation strongly influenced reported pain, but they
      did so via two distinct brain pathways. The effects of stimulus intensity were
      mediated by the neurologic pain signature (NPS), an a priori distributed brain
      network shown to predict physical pain with over 90% sensitivity and specificity
      across four studies. Self-regulation did not influence NPS responses; instead,
      its effects were mediated through functional connections between the nucleus
      accumbens and ventromedial prefrontal cortex. This pathway was unresponsive to
      noxious input, and has been broadly implicated in valuation, emotional appraisal,
      and functional outcomes in pain and other types of affective processes. These
      findings provide evidence that pain reports are associated with two dissociable
      functional systems: nociceptive/affective aspects mediated by the NPS, and
      evaluative/functional aspects mediated by a fronto-striatal system. 

PMID- 25562691
TI  - Effect of increasing the dietary tryptophan to lysine ratio on plasma levels of
      tryptophan, kynurenine and urea and on production traits in weaner pigs
      experimentally infected with an enterotoxigenic strain of Escherichia coli.
AB  - This experiment examined if immune system stimulation of weaner pigs, initiated
      by inoculation an enterotoxigenic strain of Escherichia coli (ETEC), increased
      the requirement for dietary tryptophan (Trp), modulated the inflammatory
      response, altered plasma levels of Trp and its metabolite kynurenine (Kyn) and
      effected post-weaning diarrhoea. Individually housed pigs (n = 72) weaned at 21 d
      of age were allocated to one of six treatments (n = 12) according to a two by
      three factorial arrangement of (1) with or without ETEC infection and (2) three
      dietary ratios of standardised ileal digestible (SID) Trp to lysine (Lys) (SID
      Trp:Lys) of 0.16, 0.20 or 0.24, in a completely randomised block design. Pigs had
      ad libitum access to diets (per kg 14.13 MJ ME, 12.4 g SID Lys, 195 g crude
      protein) for 3 weeks after weaning. Pigs were infected with ETEC (O149:K98:K88)
      at 72, 96 and 120 h after weaning and then bled on day 3, 11 and 19. An increased
      dietary Trp:Lys ratio increased plasma Trp and Kyn (p < 0.001) without effect of
      infection. On day 3, pigs fed 0.24 SID Trp:Lys had lower levels of plasma urea
      than at 0.20 Trp:Lys (p = 0.047) and on day 11, plasma urea was lower at 0.20
      than at 0.16 SID Trp:Lys (p = 0.007). Infection increased (p = 0.039) the
      diarrhoea index and deteriorated faecal consistency from day 4-10 (p < 0.05).
      Treatments did not affect haptoglobin and acid soluble glycoprotein levels or
      daily gain and feed intake. However, 0.24 SID Trp:Lys improved (p = 0.021) feed
      efficiency without an effect of infection. In conclusion, in the absence of
      dietary antibiotic growth promotants, increasing the dietary SID Trp:Lys ratio to
      0.24 improved feed conversion ratio after weaning and increased plasma levels of
      Trp and Kyn regardless of infection with E. coli.

PMID- 25562693
TI  - The effect of sensorimotor training on the postural stability of visually
      impaired women over 50 years of age.
AB  - Previous studies indicated that blind and visually impaired people are a group
      with greater risk of falls. Postmenopausal changes significantly decrease
      physical efficiency and impair the body's mechanisms for maintaining postural
      stability. In addition, the frequency of falls among women is much higher than in
      men. The aim of this study was to analyze the effect of sensorimotor exercise on
      changes in postural stability of visually impaired women over 50 years of age.
      Visually impaired women from group E showed a lower level of postural stability
      measured with EO compared to the healthy women. After completing the exercise, a
      more pronounced improvement in the level of postural stability was observed in
      group E. 

PMID- 25562695
TI  - Colloidal transport and diffusion over a tilted periodic potential: dynamics of
      individual particles.
AB  - A tilted two-layer colloidal system is constructed for the study of force
      assisted barrier-crossing dynamics over a periodic potential. The periodic
      potential is provided by the bottom layer colloidal spheres forming a fixed
      crystalline pattern on a glass substrate. The corrugated surface of the bottom
      colloidal crystal provides a gravitational potential field for the top layer
      diffusing particles. By tilting the sample at an angle theta with respect to the
      vertical (gravity) direction, a tangential component of the gravitational force F
      is applied to the diffusing particles. The measured mean drift velocity v(F, Eb)
      and diffusion coefficient D(F, Eb) of the particles as a function of F and energy
      barrier height Eb agree well with the exact results of the one-dimensional drift
      velocity (R. L. Stratonovich, Radiotekh. Elektron, 1958, 3, 497) and diffusion
      coefficient (P. Reimann, et al., Phys. Rev. Lett., 2001, 87, 010602 and P.
      Reimann, et al., Phys. Rev. E, 2002, 65, 031104). Based on these exact results,
      we show analytically and verify experimentally that there exists a scaling
      region, in which v(F, Eb) and D(F, Eb) both scale as nu'(F)exp[-E(F)/kBT], where
      the Arrhenius pre-factor nu'(F) and effective barrier height E(F) are both
      modified by F. The experiment demonstrates the applications of this model system
      in evaluating different scaling forms of nu'(F) and E(F) and their accuracy, in
      order to extract useful information about the external potential, such as the
      intrinsic barrier height Eb. 

PMID- 25562694
TI  - Laser printer attribution: exploring new features and beyond.
AB  - With a huge amount of printed documents nowadays, identifying their source is
      useful for criminal investigations and also to authenticate digital copies of a
      document. In this paper, we propose novel techniques for laser printer
      attribution. Our solutions do not need very high resolution scanning of the
      investigated document and explore the multidirectional, multiscale and low-level
      gradient texture patterns yielded by printing devices. The main contributions of
      this work are: (1) the description of printed areas using multidirectional and
      multiscale co-occurring texture patterns; (2) description of texture on low-level
      gradient areas by a convolution texture gradient filter that emphasizes textures
      in specific transition areas and (3) the analysis of printer patterns in segments
      of interest, which we call frames, instead of whole documents or only printed
      letters. We show by experiments in a well documented dataset that the proposed
      methods outperform techniques described in the literature and present near
      perfect classification accuracy being very promising for deployment in real-world
      forensic investigations. 

PMID- 25562692
TI  - Metabolic regulation of histone post-translational modifications.
AB  - Histone post-translational modifications regulate transcription and other DNA
      templated functions. This process is dynamically regulated by specific modifying
      enzymes whose activities require metabolites that either serve as cosubstrates or
      act as activators/inhibitors. Therefore, metabolism can influence histone
      modification by changing local concentrations of key metabolites.
      Physiologically, the epigenetic response to metabolism is important for nutrient
      sensing and environment adaption. In pathologic states, the connection between
      metabolism and histone modification mediates epigenetic abnormality in complex
      disease. In this review, we summarize recent studies of the molecular mechanisms
      involved in metabolic regulation of histone modifications and discuss their
      biological significance. 

PMID- 25562696
TI  - Concise syntheses of dictyodendrins A and F by a sequential C-H functionalization
      strategy.
AB  - Syntheses of dictyodendrins A and F have been achieved using a sequential C-H
      functionalization strategy. The N-alkylpyrrole core is fully functionalized by
      means of a rhodium(I)-catalyzed C-H arylation at the C3-position, a rhodium(II)
      catalyzed double C-H insertion at the C2- and C5-positions, and a Suzuki-Miyaura
      cross-coupling reaction at the C4-position. The syntheses of dictyodendrins A and
      F were completed by formal 6pi-electrocyclization to generate the pyrrolo[2,3
      c]carbazole core of the natural products. 

PMID- 25562698
TI  - Self-propelled chemotactic ionic liquid droplets.
AB  - Herein we report the chemotactic behaviour of self-propelled droplets composed
      solely of the ionic liquid trihexyl(tetradecyl)phosphonium chloride
      ([P(6,6,6,14)][Cl]). These droplets spontaneously move along an aqueous-air
      boundary in the direction of chloride gradients to specific destinations due to
      asymmetric release of [P(6,6,6,14)](+) cationic surfactant from the droplet into
      the aqueous phase.

PMID- 25562697
TI  - Organocatalytic enantioselective direct vinylogous Michael addition of alpha,beta
      unsaturated gamma-butyrolactam to beta-acyl acrylates and 1,2-diacylethylenes.
AB  - A highly efficient Michael addition of alpha,beta-unsaturated gamma-butyrolactam
      to various beta-acyl acrylates and ene-diones to provide synthetically useful
      compounds was developed. The products were obtained with high diastereo- and
      enantioselectivities (up to >25:1 dr and 99% ee) containing adjacent tertiary
      stereocenters. 

PMID- 25562701
TI  - A comparative study on the interaction of the putative anticancer alkaloids,
      sanguinarine and chelerythrine, with single- and double-stranded, and heat
      denatured DNAs.
AB  - A detailed investigation on the interaction of two benzophenanthridine alkaloids,
      sanguinarine (SGR) and chelerythrine (CHL), with the double-stranded (ds), heat
      denatured (hd), and single-stranded (ss) DNA was performed by spectroscopy and
      calorimetry techniques. Binding to the three DNA conformations leads to quenching
      of fluorescence of SGR and enhancement in the fluorescence of CHL. The binding
      was cooperative for both of the alkaloids with all the three DNA conformations.
      The binding constant values of both alkaloids with the ds DNA were in the order
      of 10(6) M(-1); binding was weak with hd and much weaker to the ss DNA. The
      fluorescence emission of the alkaloid molecules bound to the ds and hd DNAs was
      quenched much less compared to those bound to the ss DNA based on competition
      with the anionic quencher KI. For both double stranded and heat denatured
      structures the emission of the bound alkaloid molecules was polarized
      significantly and strong energy transfer from the DNA bases to the alkaloid
      molecules occurred. Intercalation of SGR and CHL to ds, hd, and ss DNA was proved
      from these fluorescence results. Calorimetric studies suggested that the binding
      to all DNA conformations was both enthalpy and entropy favored. Both the
      alkaloids preferred double-helical regions for binding, but SGR was a stronger
      binder than CHL to all the three DNA structures.

PMID- 25562700
TI  - Trends in Personalized Therapies in Oncology: The (Venture) Capitalist's
      Perspective.
AB  - Oncology is one of the most important fields of personalized medicine as a
      majority of efforts in this field have recently centered on targeted cancer drug
      development. New tools are continuously being developed that promise to make
      cancer treatment more efficacious while causing fewer side effects. Like most
      industries, the biopharmaceutical industry is also following certain global
      trends and these are analyzed in this article. As academia and industry are
      mutually dependent on each other, researchers in the field should be aware of
      those trends and the immediate consequences for their research. It is important
      for the future of this field that there is a healthy relationship among all
      interested parties as the challenges of personalized medicine are becoming ever
      more complex. 

PMID- 25562702
TI  - Assembly of cell-laden hydrogel fiber into non-liquefied and liquefied 3D spiral
      constructs by perfusion-based layer-by-layer technique.
AB  - In this work, three-dimensional (3D) self-sustaining, spiral-shaped constructs
      were produced through a combination of ionotropic gelation, to form cell
      encapsulated alginate fibers, and a perfusion-based layer-by-layer (LbL)
      technique. Single fibers were assembled over cylindrical molds by reeling to form
      spiral shapes, both having different geometries and sizes. An uninterrupted
      nanometric multilayer coating produced by a perfusion-based LbL technique, using
      alginate and chitosan, generated stable 3D spiral-shaped macrostructures by
      gripping and affixing the threads together without using any crosslinking/binding
      agent. The chelation process altered the internal microenvironment of the 3D
      construct from the solid to the liquefied state while preserving the external
      geometry. L929 cell viability by MTS and dsDNA quantification favor liquefied 3D
      constructs more than non-liquefied ones. The proposed technique setup helps us to
      generate complex polyelectrolyte-based 3D constructs for tissue engineering
      applications and organ printing. 

PMID- 25562699
TI  - Personalized medicine and cancer.
AB  - Cancer is one of the leading causes of death in the United States, and more than
      1.5 million new cases and more than 0.5 million deaths were reported during 2010
      in the United States alone. Following completion of the sequencing of the human
      genome, substantial progress has been made in characterizing the human epigenome,
      proteome, and metabolome; a better understanding of pharmacogenomics has been
      developed, and the potential for customizing health care for the individual has
      grown tremendously. Recently, personalized medicine has mainly involved the
      systematic use of genetic or other information about an individual patient to
      select or optimize that patient's preventative and therapeutic care. Molecular
      profiling in healthy and cancer patient samples may allow for a greater degree of
      personalized medicine than is currently available. Information about a patient's
      proteinaceous, genetic, and metabolic profile could be used to tailor medical
      care to that individual's needs. A key attribute of this medical model is the
      development of companion diagnostics, whereby molecular assays that measure
      levels of proteins, genes, or specific mutations are used to provide a specific
      therapy for an individual's condition by stratifying disease status, selecting
      the proper medication, and tailoring dosages to that patient's specific needs.
      Additionally, such methods can be used to assess a patient's risk factors for a
      number of conditions and to tailor individual preventative treatments. Recent
      advances, challenges, and future perspectives of personalized medicine in cancer
      are discussed. 

PMID- 25562704
TI  - The effect of suture characteristics on short-term morbidity after vaginal
      prolapse surgery.
AB  - Previous studies suggest that larger sutures increase the risk of complications
      after prolapse surgery. This study aimed to assess whether multifilament sutures
      increased complications compared with monofilament sutures. A series of 100 women
      with 2/0 multifilament suture were matched by operation to a previous cohort when
      a size 2/0 monofilament suture was used. Offensive vaginal discharge was more
      common in the multifilament than in the monofilament group (24% vs. 12%; p =
      0.04). However, there was no increased requirement to seek advice from a health
      professional (33% vs. 25%; p = 0.27) or to require antibiotics. Vaginal bleeding
      (10% vs. 5%; p = 0.28) and urinary infection (2% vs. 5%; p = 0.44) were
      statistically no more common in the multifilament 2/0 compared with the
      monofilament 2/0 group. Multifilament sutures used for closure of the vaginal
      skin are associated with a clinically non-significant higher incidence of vaginal
      discharge in the early post-operative period. 

PMID- 25562705
TI  - Full-Sun observations for identifying the source of the slow solar wind.
AB  - Fast (>700 km s(-1)) and slow (~400 km s(-1)) winds stream from the Sun, permeate
      the heliosphere and influence the near-Earth environment. While the fast wind is
      known to emanate primarily from polar coronal holes, the source of the slow wind
      remains unknown. Here we identify possible sites of origin using a slow solar
      wind source map of the entire Sun, which we construct from specially designed,
      full-disk observations from the Hinode satellite, and a magnetic field model. Our
      map provides a full-Sun observation that combines three key ingredients for
      identifying the sources: velocity, plasma composition and magnetic topology and
      shows them as solar wind composition plasma outflowing on open magnetic field
      lines. The area coverage of the identified sources is large enough that the sum
      of their mass contributions can explain a significant fraction of the mass loss
      rate of the solar wind.

PMID- 25562703
TI  - The Milieu Interieur study - an integrative approach for study of human
      immunological variance.
AB  - The Milieu Interieur Consortium has established a 1000-person healthy population
      based study (stratified according to sex and age), creating an unparalleled
      opportunity for assessing the determinants of human immunologic variance. Herein,
      we define the criteria utilized for participant enrollment, and highlight the key
      data that were collected for correlative studies. In this report, we analyzed
      biological correlates of sex, age, smoking-habits, metabolic score and CMV
      infection. We characterized and identified unique risk factors among healthy
      donors, as compared to studies that have focused on the general population or
      disease cohorts. Finally, we highlight sex-bias in the thresholds used for
      metabolic score determination and recommend a deeper examination of current
      guidelines. In sum, our clinical design, standardized sample collection
      strategies, and epidemiological data analyses have established the foundation for
      defining variability within human immune responses. 

PMID- 25562706
TI  - On-chip hybrid photonic-plasmonic light concentrator for nanofocusing in an
      integrated silicon photonics platform.
AB  - The enhancement and confinement of electromagnetic radiation to nanometer scale
      have improved the performances and decreased the dimensions of optical sources
      and detectors for several applications including spectroscopy, medical
      applications, and quantum information. Realization of on-chip nanofocusing
      devices compatible with silicon photonics platform adds a key functionality and
      provides opportunities for sensing, trapping, on-chip signal processing, and
      communications. Here, we discuss the design, fabrication, and experimental
      demonstration of light nanofocusing in a hybrid plasmonic-photonic nanotaper
      structure. We discuss the physical mechanisms behind the operation of this
      device, the coupling mechanisms, and how to engineer the energy transfer from a
      propagating guided mode to a trapped plasmonic mode at the apex of the plasmonic
      nanotaper with minimal radiation loss. Optical near-field measurements and
      Fourier modal analysis carried out using a near-field scanning optical microscope
      (NSOM) show a tight nanofocusing of light in this structure to an extremely small
      spot of 0.00563(lambda/(2n(rmax)))(3) confined in 3D and an exquisite power input
      conversion of 92%. Our experiments also verify the mode selectivity of the device
      (low transmission of a TM-like input mode and high transmission of a TE-like
      input mode). A large field concentration factor (FCF) of about 4.9 is estimated
      from our NSOM measurement with a radius of curvature of about 20 nm at the apex
      of the nanotaper. The agreement between our theory and experimental results
      reveals helpful insights about the operation mechanism of the device, the
      interplay of the modes, and the gradual power transfer to the nanotaper apex. 

PMID- 25562707
TI  - Cognitive predictors of copying and drawing from memory of the Rey-Osterrieth
      complex figure in 7- to 10-year-old children.
AB  - Cognitive models of drawing are mainly based on assessment of copying performance
      of adults, whereas only a few studies have verified these models in young
      children. Moreover, developmental investigations have only rarely performed a
      systematic examination of the contribution of perceptual and representational
      visuo-spatial processes to copying and drawing from memory. In this study we
      investigated the role of visual perception and mental representation in both
      copying and drawing from memory skills in a sample of 227 typically developing
      children (53% females) aged 7-10 years. Participants underwent a
      neuropsychological assessment and the Rey-Osterrieth Complex Figure (ROCF). The
      fit and invariance of the predictive model considering visuo-spatial abilities,
      working memory, and executive functions were tested by means of hierarchical
      regressions and path analysis. Results showed that, in a gender invariant way,
      visual perception abilities and spatial mental representation had a direct effect
      on copying performance, whereas copying performance was the only specific
      predictor for drawing from memory. These effects were independent from age and
      socioeconomic status, and showed that cognitive models of drawing built up for
      adults could be considered for predicting copying and drawing from memory in
      children. 

PMID- 25562708
TI  - Mechanistic insights into the vanadium-catalyzed Achmatowicz rearrangement of
      furfurol.
AB  - The Achmatowicz rearrangement is a powerful method for the construction of
      pyranones from simple furan derivatives. Here, we describe the development of
      improved reaction conditions and an interrogation into the fate of the metal
      center during this interesting transformation. The reaction to form the
      synthetically important lactol, 6-hydroxy-2H-pyran-3(6H)-one (3), proceeds
      cleanly in the presence of tert-butyl hydroperoxide (TBHP, 2) using low loadings
      of VO(O(i)Pr)3 as catalyst. The nonaqueous conditions developed herein allow for
      easy isolation of product 3 and synthetically important derivatives, a key
      advantage of this new protocol. Detailed experimental, spectroscopic, and kinetic
      studies along with kinetic modeling of the catalytic cycle support a positive
      order dependence in both furfurol and TBHP concentrations, first-order dependence
      in catalyst (VO(O(i)Pr)3), and a negative dependence on the 2-methyl-2-propanol
      (4) concentration. (51)V-NMR spectroscopic studies revealed that 2-methyl-2
      propanol (4) competes with substrates for binding to the metal center,
      rationalizing its inhibitory effect. 

PMID- 25562709
TI  - Correction: Non-faradaic impedance characterization of an evaporating droplet for
      microfluidic and biosensing applications.
AB  - Correction for 'Non-faradaic impedance characterization of an evaporating droplet
      for microfluidic and biosensing applications' by Piyush Dak et al., Lab Chip,
      2014, 14, 2469-2479. 

PMID- 25562710
TI  - Procedural learning, consolidation, and transfer of a new skill in Developmental
      Coordination Disorder.
AB  - The aim of this study was to explore the differences in procedural learning
      abilities between children with DCD and typically developing children by
      investigating the steps that lead to skill automatization (i.e., the stages of
      fast learning, consolidation, and slow learning). Transfer of the skill to a new
      situation was also assessed. We tested 34 children aged 6-12 years with and
      without DCD on a perceptuomotor adaptation task, a form of procedural learning
      that is thought to involve the cerebellum and the basal ganglia (regions whose
      impairment has been associated with DCD) but also other brain areas including
      frontal regions. The results showed similar rates of learning, consolidation, and
      transfer in DCD and control children. However, the DCD children's performance
      remained slower than that of controls throughout the procedural task and they
      reached a lower asymptotic performance level; the difficulties observed at the
      outset did not diminish with practice. 

PMID- 25562712
TI  - Long-term effects of oxandrolone treatment in childhood on neurocognition,
      quality of life and social-emotional functioning in young adults with Turner
      syndrome.
AB  - Turner syndrome (TS) is the result of (partial) absence of one X-chromosome.
      Besides short stature, gonadal dysgenesis and other physical aspects, TS women
      have typical psychological features. Since psychological effects of androgen
      exposure in childhood probably are long-lasting, we explored long-term
      psychological functioning after oxandrolone (Ox) therapy during childhood in
      adults with TS in terms of neurocognition, quality of life and social-emotional
      functioning. During the initial study, girls were treated with growth hormone
      (GH) combined with placebo (Pl), Ox 0.03 mg/kg/day, or Ox 0.06 mg/kg/day from the
      age of eight, and estrogen from the age of twelve. Sixty-eight women participated
      in the current double-blinded follow-up study (mean age 24.0 years, mean time
      since stopping GH/Ox 8.7 years). We found no effects on neurocognition.
      Concerning quality of life women treated with Ox had higher anxiety levels (STAI
      37.4 +/- 8.4 vs 31.8 +/- 5.0, p=0.002) and higher scores on the depression
      subscale of the SCL-90-R (25.7 +/- 10.7 vs 20.5 +/- 4.7, p=0.01). Regarding
      social-emotional functioning, emotion perception for fearful faces was lower in
      the Ox-treated patients, without effect on interpersonal behavior. Our
      exploratory study is the first to suggest that androgen treatment in adolescence
      possibly has long-term effects on adult quality of life and social-emotional
      functioning. However, differences are small and clinical implications of our
      results seem limited. Therefore we would not recommend against the use of Ox in
      light of psychological consequences.

PMID- 25562711
TI  - Oxytocin increases VTA activation to infant and sexual stimuli in nulliparous and
      postpartum women.
AB  - After giving birth, women typically experience decreased sexual desire and
      increased responsiveness to infant stimuli. These postpartum changes may be
      viewed as a trade-off in reproductive interests, which could be due to
      alterations in brain activity including areas associated with reward. The goal of
      this study was to describe the roles of oxytocin and parity on reward area
      activation in response to reproductive stimuli, specifically infant and sexual
      images. Because they have been shown to be associated with reward, the ventral
      tegmental area (VTA) and nucleus accumbens (NAc) were targeted as areas of
      expected alterations in activity. Oxytocin was chosen as a potential mediator of
      reproductive trade-offs because of its relationship to both mother-infant
      interactions, including breastfeeding and bonding, and sexual responses. We
      predicted that postpartum women would show higher reward area activation to
      infant stimuli and nulliparous women would show higher activation to sexual
      stimuli and that oxytocin would increase activation to infant stimuli in
      nulliparous women. To test this, we measured VTA and NAc activation using fMRI in
      response to infant photos, sexual photos, and neutral photos in 29 postpartum and
      30 nulliparous women. Participants completed the Sexual Inhibition (SIS) and
      Sexual Excitation (SES) Scales and the Brief Index of Sexual Function for Women
      (BISF-W), which includes a sexual desire dimension, and received either oxytocin
      or placebo nasal spray before viewing crying and smiling infant and sexual images
      in an fMRI scanner. For both groups of women, intranasal oxytocin administration
      increased VTA activation to both crying infant and sexual images but not to
      smiling infant images. We found that postpartum women showed lower SES, higher
      SIS, and lower sexual desire compared to nulliparous women. Across parity groups,
      SES scores were correlated with VTA activation and subjective arousal ratings to
      sexual images. In postpartum women, sexual desire was positively correlated with
      VTA activation to sexual images and with SES. Our findings show that postpartum
      decreases in sexual desire may in part be mediated by VTA activation, and
      oxytocin increased activation of the VTA but not NAc in response to sexual and
      infant stimuli. Oxytocin may contribute to the altered reproductive priorities in
      postpartum women by increasing VTA activation to salient infant stimuli. 

PMID- 25562714
TI  - Effects of angiotensin type 2 receptor on secretion of the locus coeruleus in
      stress-induced hypertension rats.
AB  - Locus coeruleus (LC) has noradrenergic nerve terminals projecting to hypothalamus
      that modulating cardiovascular activity. To study the dynamic characteristics of
      norepinephrine (NE) release in hypothalamus followed by electrical stimulation in
      the locus coeruleus in the stress-induced hypertension (SIH) rats, we established
      the hypertension model rats by stimulations combining noise and foot-shock
      stress. After the end of modeling, NE release in the hypothalamus by electrical
      stimulation in LC was studied and NE signal was recorded by carbon fiber
      electrode. The peak value, the time to peak and half-life period of NE signal in
      both group rats were analyzed. Furthermore, to clarify the role of angiotensin II
      type 2 receptors (AT2) in norepinephrine (NE) release and the blood pressure of
      rat model of stress-induced hypertension, we intraperitoneally administered the
      AT2 receptor antagonist PD123319 (AT2 receptor antagonist, 0.3mg/kg, i.p.) and
      intracerebroventricularly injection of CGP42112 (AT2 receptor agonist, 6MUg/5MUl,
      i.c.v.) to adult male rats. We found the peak value of NE signal in the
      hypothalamus followed by electrical stimulation in the LC in SIH rats were higher
      than that in controls (P<0.01). Intraperitoneal injection of PD123319 (AT2
      receptor antagonist) potentiated electrical stimulation in the LC induced NE
      release in the hypothalamus in SIH rats and elevated blood pressure (P<0.05),
      whereas intracerebroventricular injection of CGP42112 (AT2 receptor agonist)
      inhibited the NE release and reduced the heart rate (P<0.05). These results
      suggest that combining noise and foot-shock stresses increased the blood pressure
      and the secretion of NE in the hypothalamus followed by electrical stimulation in
      the LC in rats. AT2 receptors can inhibit the secretion of NE from the LC to the
      hypothalamus. The attenuation of presynaptic action of AT2 receptor may play a
      role in the pathophysiological mechanism of SIH in rats. 

PMID- 25562713
TI  - Preparation, characterization, and properties of PMMA-doped polymer film
      materials: a study on the effect of terbium ions on luminescence and lifetime
      enhancement.
AB  - Poly(methylmethacrylate) (PMMA) doped with Tb-based imidazole derivative
      coordination polymer {[Tb(3)(L)(MU(3)-OH)(7)].H(2)O}(n) (1) (L = N,N'
      bis(acetoxy)biimidazole) was synthesized and its photophysical properties were
      studied. The L'(L' = N,N'-bis(ethylacetate)biimidazole) ligand was synthesized by
      an N-alkylation reaction process followed by ester hydrolysis to produce ligand
      L. Polymer 1 and ligand L' have been characterized by (1)H NMR and IR
      spectroscopy, elemental analysis, PXRD and X-ray single-crystal diffraction.
      Coordination polymer 1 is the first observation of a CdCl(2) structure
      constructed with hydroxy groups and decorated by ligand L in lanthanide N
      heterocyclic coordination polymers. In the 2D layered structure of 1, each Tb3
      metal center is connected with three Tb1 and three Tb2 metal centers by seven
      hydroxyl groups in different directions, resulting in a six-membered ring. After
      doping, not only the luminescence intensity and lifetime enhanced, but also their
      thermal stability was increased in comparison with 1. When 1 was doped into
      poly(methylmethacrylate) (1@PMMA), polymer film materials were formed with the
      PMMA polymer matrix (w/w = 2.5%-12.5%) acting as a co-sensitizer for Tb(3+) ions.
      The luminescence intensity of the Tb(3+) emission at 544 nm increases when the
      content of Tb(3+) was 10%. The lifetime of 1@PMMA (914.88 MUs) is more than four
      times longer than that of 1 (196.24 MUs). All tau values for the doped polymer
      systems are higher than coordination polymer 1, indicating that radiative
      processes are operative in all the doped polymer films. This is because PMMA
      coupling with the O-H oscillators from {[Tb(3)(L)(MU(3)-OH)(7)].H(2)O}(n) can
      suppress multiphonon relaxation. According to the variable-temperature
      luminescence (VT-luminescence) investigation, 1@PMMA was confirmed to be a stable
      green luminescent polymer film material.

PMID- 25562716
TI  - Unusual dealloying effect in gold/copper alloy thin films: the role of defects
      and column boundaries in the formation of nanoporous gold.
AB  - Understanding the dealloying mechanisms of gold-based alloy thin films resulting
      in the formation of nanoporous gold with a sponge-like structure is essential for
      the future design and integration of this novel class of material in practical
      devices. Here we report on the synthesis of nanoporous gold thin films using a
      free-corrosion approach in nitric acid applied to cosputtered Au-Cu thin films. A
      relationship is established between the as-grown Au-Cu film characteristics
      (i.e., composition, morphology, and structure) and the porosity of the sponge
      like gold thin films. We further demonstrate that the dealloying approach can be
      applied to nonhomogenous Au-Cu alloy thin films consisting of periodic and
      alternate Au-rich/Au-poor nanolayers. In such a case, however, the dealloying
      process is found to be altered and unusual etching stages arise. Thanks to
      defects and column boundaries playing the role of channels, the nitric acid is
      found to quickly penetrate within the films and then laterally (i.e., parallel to
      the film surface) attacks the nanolayers rather than perpendicularly. As a
      consequence to this anisotropic etching, the Au-poor layers are etched
      preferentially and transform into Au pillars holding the Au-rich layers and
      preventing them against collapsing. A further exposure to nitric acid results in
      the collapsing of the Au-rich layers accompanied by a transition from a
      multilayered to a sponge-like structure. A scenario, supported by experimental
      observations, is further proposed to provide a detailed explanation of the
      fundamental mechanisms occurring during the dealloying process of films with a
      multilayered structure. 

PMID- 25562715
TI  - Impaired corticostriatal LTP and depotentiation following iPLA2 inhibition is
      restored following acute application of DHA.
AB  - Docosahexaenoic acid (DHA) is a 22 carbon, six cis-double bonded (22:6, w3) omega
      3 polyunsaturated acid (PUFA), found highly enriched with neuronal membranes, and
      believed to play a critical role in synaptic plasticity and cognitive correlates
      of learning and memory. DHA is released from the neuronal membrane via the action
      of the cytostolic calcium-independent phospholipase A2 (iPLA2) enzyme. Previous
      studies have demonstrated that inhibition of iPLA2 by bromoenol lactone (BEL),
      results in inhibition of CA1 long-term potentiation (LTP), restored following
      acute application of DHA. In the present study, we investigated the effect of
      selective iPLA2 inhibition and acute application of DHA on corticostriatal
      synaptic plasticity. We demonstrate that acute application of 30MUM DHA
      facilitates cotricostriatal LTP, whilst long-term depression (LTD), basal
      transmission, and paired-pulse facilitation (PPF) are unaffected. Conversely,
      selective inhibition of iPLA2, via acute application of 10MUM BEL, inhibits the
      expression of corticostriatal LTP, with no effect on LTD. Furthermore, we show
      that 10MUM BEL inhibition of LTP is reversed following acute application of 30MUM
      DHA. Finally, we demonstrate that 10MUM BEL inhibits depotentiation of
      corticostriatal LTP, which is restored following acute application of 30MUM DHA.
      Our findings indicate that appropriate release of DHA is a critical facet of
      corticostriatal LTP and depotentiation, and thus provides an exciting cellular
      target for the positive facilitation of cognitive function observed following DHA
      dietary supplementation. 

PMID- 25562718
TI  - Development of a ReaxFF potential for carbon condensed phases and its application
      to the thermal fragmentation of a large fullerene.
AB  - In this article, we report the development of a ReaxFF reactive potential that
      can accurately describe the chemistry and dynamics of carbon condensed phases.
      Density functional theory (DFT)-based calculations were performed to obtain the
      equation of state for graphite and diamond and the formation energies of defects
      in graphene and amorphous phases from fullerenes. The DFT data were used to
      reparametrize ReaxFFCHO, resulting in a new potential called ReaxFFC-2013.
      ReaxFFC-2013 accurately predicts the atomization energy of graphite and closely
      reproduces the DFT-based energy difference between graphite and diamond, and the
      barrier for transition from graphite to diamond. ReaxFFC-2013 also accurately
      predicts the DFT-based energy barrier for Stone-Wales transformation in a C60(Ih)
      fullerene through the concerted rotation of a C2 unit. Later, MD simulations of a
      C180 fullerene using ReaxFFC-2013 suggested that the thermal fragmentation of
      these giant fullerenes is an exponential function of time. An Arrhenius-type
      equation was fit to the decay rate, giving an activation energy of 7.66 eV for
      the loss of carbon atoms from the fullerene. Although the decay of the molecule
      occurs primarily via the loss of C2 units, we observed that, with an increase in
      temperature, the probability of loss of larger fragments increases. The ReaxFFC
      2013 potential developed in this work, and the results obtained on fullerene
      fragmentation, provide an important step toward the full computational chemical
      modeling of coal pyrolysis, soot incandescence, high temperature erosion of
      graphitic rocket nozzles, and ablation of carbon-based spacecraft materials
      during atmospheric reentry. 

PMID- 25562717
TI  - Direct enantioselective conjugate addition of carboxylic acids with chiral
      lithium amides as traceless auxiliaries.
AB  - Michael addition is a premier synthetic method for carbon-carbon and carbon
      heteroatom bond formation. Using chiral dilithium amides as traceless
      auxiliaries, we report the direct enantioselective Michael addition of carboxylic
      acids. A free carboxyl group in the product provides versatility for further
      functionalization, and the chiral reagent can be readily recovered by extraction
      with aqueous acid. The method has been applied in the enantioselective total
      synthesis of the purported structure of pulveraven B. 

PMID- 25562719
TI  - Melkersson-Rosenthal syndrome with involvement of masticatory muscles.

PMID- 25562720
TI  - A long-life Na-air battery based on a soluble NaI catalyst.
AB  - A Na-air battery with NaI dissolved in a typical organic electrolyte could run up
      to 150 cycles with a capacity limit of 1000 mA h g(-1). The low charge voltage
      plateau of 3.2 V vs. Na(+)/Na in a Na-air battery should mainly be attributed to
      the oxidation reaction of active iodine anions. 

PMID- 25562721
TI  - Hydroethanolic extract of the inner stem bark of Cedrela odorata has low toxicity
      and reduces hyperglycemia induced by an overload of sucrose and glucose.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cedrela odorata L. (Meliaceae) is a native plant
      of the Amazon region and its inner stem bark is used in the treatment of diabetes
      in the form of maceration in Brazilian popular medicine. Until now, there is no
      scientific study on this activity. The present study was aimed at evaluating the
      anti-hyperglycemic activity, anti-diabetic, toxicity, antioxidant and potential
      mechanism of action of hydroethanolic extract of the inner stem bark of Cedrela
      odorata. MATERIAL AND METHODS: The inner stem bark extract of Cedrela odorata was
      prepared by maceration in 70% ethanol for 7 days to obtain hydroethanolic extract
      of Cedrela odorata (HeECo). The preliminary phytochemical analysis was performed
      according to procedures described in the literature. Selected secondary
      metabolites detected were quantified by high performance liquid chromatography
      (HPLC). Acute toxicity of HeECo was investigated in male and female mice with
      oral administration of graded doses of HeECo from 10 to 5000 mg/kg. Subchronic
      oral toxicity study was done by oral administration of HeECo (500 mg/kg) and
      vehicle for 30 days to both sexes of Wistar rats. Clinical observations and
      toxicological related parameters were determined. Blood was collected for
      biochemical and hematological analyses, while histological examinations were
      performed on selected organs. Anti-hiperglycemic and antidiabetic effects were
      evaluated in streptozotocin-induced diabetic rats. In acute evaluation, the
      animals received pretreatment with 250 and 500 mg/kg of HeECo, before
      carbohydrate overload. For subchronic effect, the antidiabetic activity of HeECo
      was evaluated using the same doses for 21 days. At the end of the treatments, the
      levels of triacylglycerols, malondialdehyde, total antioxidant status, superoxide
      dismutase and glutathione peroxidase activities were evaluated in the plasma.
      RESULTS: The extract showed low acute toxicity. HeECo exhibited inhibitory
      activity against alpha-glucosidase and caused a lowering in the peak levels of
      blood glucose in animals that received glucose overload by 36.7% and 24.1% in the
      area under the glucose curve (AUC). When the overload was sucrose, HeECo reduced
      the blood glucose level by 44.4% without affecting AUC. Treatment with HeECo of
      the blood glucose of the diabetic animals for 21 days did not lead to improvement
      in weight gain and regularization of the blood glucose level, but reduced the
      triacylglycerol and malondialdehyde levels by 36.6% and 48.1%, respectively. The
      activity of the antioxidant enzymes, superoxide dismutase and glutathione
      peroxidase were significantly increased when compared to diabetic control rats.
      HPLC analysis showed the presence of polyphenols, such as gallic acid, (-)-
      gallocatechin and (+)- catechin, the latter is present in higher quantity.
      CONCLUSIONS: Collectively, these data showed that HeECo could blunt the
      postprandial glycemic surge in rats; possibly through inhibition of alpha
      glucosidase and positive modulation of antioxidant enzymes. Our findings
      confirmed the anti-hiperglycemic activity of HeECo in STZ- diabetic rats. Cedrela
      odorata is effective in diminishing glucose levels in vitro and in vivo and in
      ameliorating oxidative damage that occurs in diabetes and/or due to hyperglycemia
      in rats. According to our results, the efficacy of Cedrela odorata preparation
      could be due to the presence of active principles with different mode of actions
      at the molecular level, including alpha-glycosidases and glucose transporter
      inhibitors and antioxidant property.

PMID- 25562722
TI  - Pennogenyl saponins induce cell cycle arrest and apoptosis in human
      hepatocellular carcinoma HepG2 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pennogenyl saponins, the characterized components
      of Rhizoma Paridis, have been reported to have anticancer activity through
      induction of apoptosis or anti-metastasis in cultured cells or animal models. The
      aim of the study was to evaluate the anticancer properties of four pennogenyl
      saponins (PS1-PS4) on a panel of human cancer and normal cell lines, and explore
      the potential mechanisms underlying the selective anticancer effects of the
      steroidal saponins in cancer cells. MATERIALS AND METHODS: Differences in the
      anticancer activity of pennogenyl saponins were examined by MTT assay in human
      cancer cell lines (HepG2 hepatocellular carcinoma cells, UACC-257 melanoma cells,
      MCF-7 breast and PC-3 prostate cancer cells) and normal human cell lines (L-02
      liver cells and HEK293 kidney cells). Flow cytometry analysis, JC-1 staining and
      western blot analysis were applied to detect the effects of anticancer pennogenyl
      saponins on apoptosis, cell cycle, and expression and/or activation of main
      effectors involved in the potential signaling pathways. RESULTS: Among the tested
      four saponins, only PS1 and PS2 selectively inhibited cell growth in HepG2, MCF-7
      and PC-3 cells. Moreover, PS1 and PS2 could significantly induce apoptosis and
      cell cycle G2/M arrest in HepG2 cells, which were at least associated with
      activation of mitochondrial caspase-dependent and -independent apoptotic
      cascades, inhibition of cyclin-dependent kinase 1 and PI3K/Akt signaling pathway,
      and modulation of mitogen-activated protein kinases. CONCLUSIONS: PS1 and PS2 had
      potent and selective anticancer activity to breast, liver and prostate cancer
      cells. Furthermore, the anticancer effects of PS1 and PS2 were associated with
      induction of apoptosis and blockage of cell cycle progression through multiple
      targets in HepG2 cells. These findings suggest that PS1 and PS2 can be considered
      as potential agents for the treatment of some cancers such as hepatoma.

PMID- 25562723
TI  - Potent substances-An introduction.

PMID- 25562724
TI  - Ambulatory continuous interscalene blocks for cancer pain.
AB  - Continuous peripheral nerve blocks are used in the management of pain following
      surgical procedures. They can also be used in patients with cancer-related pain,
      to improve sleep quality, reduce opioid requirements and their side effects. We
      describe two cancer patients in whom interscalene brachial plexus catheters were
      used on an outpatient basis, allowing them to travel, decrease their opioid use,
      and improve their ability to perform routine activities. 

PMID- 25562725
TI  - CYP2D6 phenotype-specific codeine population pharmacokinetics.
AB  - Codeine's metabolic fate in the body is complex, and detailed quantitative
      knowledge of it, and that of its metabolites is lacking among prescribers. We
      aimed to develop a codeine pharmacokinetic pathway model for codeine and its
      metabolites that incorporates the effects of genetic polymorphisms. We studied
      the phenotype-specific time courses of plasma codeine, codeine-6-glucoronide,
      morphine, morphine-3-glucoronide, and morphine-6-glucoronide. A codeine
      pharmacokinetic pathway model accurately fit the time courses of plasma codeine
      and its metabolites. We used this model to build a population pharmacokinetic
      codeine pathway model. The population model indicated that about 10% of a codeine
      dose was converted to morphine in poor-metabolizer phenotype subjects. The model
      also showed that about 40% of a codeine dose was converted to morphine in EM
      subjects, and about 51% was converted to morphine in ultrarapid-metabolizers. The
      population model further indicated that only about 4% of MO formed from codeine
      was converted to morphine-6-glucoronide in poor-metabolizer phenotype subjects.
      The model also showed that about 39% of the MO formed from codeine was converted
      to morphine-6-glucoronide in extensive-metabolizer phenotypes, and about 58% was
      converted in ultrarapid-metabolizers. We conclude, a population pharmacokinetic
      codeine pathway model can be useful because beyond helping to achieve a
      quantitative understanding the codeine and MO pathways, the model can be used for
      simulation to answer questions about codeine's pharmacogenetic-based disposition
      in the body. Our study suggests that pharmacogenetics for personalized dosing
      might be most effectively advanced by studying the interplay between
      pharmacogenetics, population pharmacokinetics, and clinical pharmacokinetics. 

PMID- 25562726
TI  - Engineering amyloid fibrils from beta-solenoid proteins for biomaterials
      applications.
AB  - Nature provides numerous examples of self-assembly that can potentially be
      implemented for materials applications. Considerable attention has been given to
      one-dimensional cross-beta or amyloid structures that can serve as templates for
      wire growth or strengthen materials such as glue or cement. Here, we demonstrate
      controlled amyloid self-assembly based on modifications of beta-solenoid
      proteins. They occur naturally in several contexts (e.g., antifreeze proteins,
      drug resistance proteins) but do not aggregate in vivo due to capping structures
      or distortions at their ends. Removal of these capping structures and
      regularization of the ends of the spruce budworm and rye grass antifreeze
      proteins yield micron length amyloid fibrils with predictable heights, which can
      be a platform for biomaterial-based self-assembly. The design process, including
      all-atom molecular dynamics simulations, purification, and self-assembly
      procedures are described. Fibril formation with the predicted characteristics is
      supported by evidence from thioflavin-T fluorescence, circular dichroism, dynamic
      light scattering, and atomic force microscopy. Additionally, we find evidence for
      lateral assembly of the modified spruce budworm antifreeze fibrils with
      sufficient incubation time. The kinetics of polymerization are consistent with
      those for other amyloid formation reactions and are relatively fast due to the
      preformed nature of the polymerization nucleus. 

PMID- 25562727
TI  - Rapid collection of biospecimens by automated identification of patients eligible
      for pharmacoepigenetic studies.
AB  - Epigenetics plays an important role in regulating gene expression, and can be
      modified by environmental factors and physiological conditions. Studying
      epigenetics is a promising approach to potentially improving the diagnosis,
      prevention and treatment of human diseases, and to providing personalized medical
      care. However, the role of epigenetics in the development of diseases is not
      clear because epigenetic markers may be both mediators and outcomes of human
      diseases. It is particularly complicated to study pharmacoepigenetics, as
      medication use may modify the epigenetic profile. To address the challenges
      facing pharmacoepigenetic research of human diseases, we developed a novel design
      to rapidly identify, contact, and recruit participants and collect specimens for
      longitudinal studies of pharmacoepigenetics. Using data in real-time from
      electronic medical record systems, we can identify patients recently start on new
      medications and who also have a blood test. Prior to disposal of the leftover
      blood by the clinical laboratory, we are able to contact and recruit these
      patients, enabling us to use both their leftover baseline blood sample as well as
      leftover specimens at future tests. With treatment-naive and follow-up specimens,
      this system is able to study both epigenetic markers associated with disease
      without treatment effect as well as treatment-related epigenetic changes. 

PMID- 25562728
TI  - Attitudes towards Social Networking and Sharing Behaviors among Consumers of
      Direct-to-Consumer Personal Genomics.
AB  - Little is known about how consumers of direct-to-consumer personal genetic
      services share personal genetic risk information. In an age of ubiquitous online
      networking and rapid development of social networking tools, understanding how
      consumers share personal genetic risk assessments is critical in the development
      of appropriate and effective policies. This exploratory study investigates how
      consumers share personal genetic information and attitudes towards social
      networking behaviors. METHODS: Adult participants aged 23 to 72 years old who
      purchased direct-to-consumer genetic testing from a personal genomics company
      were administered a web-based survey regarding their sharing activities and
      social networking behaviors related to their personal genetic test results.
      RESULTS: 80 participants completed the survey; of those, 45% shared results on
      Facebook and 50.9% reported meeting or reconnecting with more than 10 other
      individuals through the sharing of their personal genetic information. For help
      interpreting test results, 70.4% turned to Internet websites and online sources,
      compared to 22.7% who consulted their healthcare providers. Amongst participants,
      51.8% reported that they believe the privacy of their personal genetic
      information would be breached in the future. CONCLUSION: Consumers actively
      utilize online social networking tools to help them share and interpret their
      personal genetic information. These findings suggest a need for careful
      consideration of policy recommendations in light of the current ambiguity of
      regulation and oversight of consumer initiated sharing activities.

PMID- 25562729
TI  - Understanding the economic value of molecular diagnostic tests: case studies and
      lessons learned.
AB  - Ten years after completion of the Human Genome Project, progress towards making
      "personalized medicine" a reality has been slower than expected. The reason is
      twofold. Firstly, the science is more difficult than expected. Secondly, limited
      progress has been made in aligning economic incentives to invest in diagnostics.
      This paper develops nine case studies of "success" where diagnostic tests are
      bringing personalized medicine into clinical practice with health and economic
      impact for patients, healthcare systems, and manufacturers. We focus on the
      availability of evidence for clinical utility, which is important not only for
      clinicians but also for payers and budget holders. We find that demonstrating
      diagnostic clinical utility and the development of economic evidence is currently
      feasible (i) through drug-diagnostic co-development, and (ii) when the research
      is sponsored by payers and public bodies. It is less clear whether the diagnostic
      industry can routinely undertake the work necessary to provide evidence as to the
      clinical utility and economic value of its products. It would be good public
      policy to increase the economic incentives to produce evidence of clinical
      utility: otherwise, opportunities to generate value from personalized medicine-in
      terms of both cost savings and health gains-may be lost. 

PMID- 25562730
TI  - Application of drug testing using exhaled breath for compliance monitoring of
      drug addicts in treatment.
AB  - AIM: Exhaled breath has recently been identified as a possible matrix for drug
      testing. This study explored the potential of this new method for compliance
      monitoring of patients being treated for dependence disorders. METHODS:
      Outpatients in treatment programs were recruited for this study. Urine was
      collected as part of clinical routine and a breath sample was collected in
      parallel together with a questionnaire about their views of the testing
      procedure. Urine was analyzed for amphetamines, benzodiazepines, cannabis,
      cocaine, buprenorphine, methadone and opiates using CEDIA immunochemical
      screening and mass spectrometry confirmation. The exhaled breath was collected
      using the SensAbues device and analyzed by mass spectrometry for amphetamine,
      methamphetamine, diazepam, oxazepam, tetrahydrocannabinol, cocaine,
      benzoylecgonine, buprenorphine, methadone, morphine, codeine and 6
      acetylmorphine. RESULTS: A total of 122 cases with parallel urine and breath
      samples were collected; 34 of these were negative both in urine and breath. Out
      of 88 cases with positive urine samples 51 (58%) were also positive in breath.
      Among the patients on methadone treatment, all were positive for methadone in
      urine and 83% were positive in breath. Among patients in treatment with
      buprenorphine, 92% were positive in urine and among those 80% were also positive
      in breath. The questionnaire response documented that in general, patients
      accepted drug testing well and that the breath sampling procedure was preferred.
      CONCLUSION: Compliance testing for the intake of prescribed and unprescribed
      drugs among patients in treatment for dependence disorders using the exhaled
      breath sampling technique is a viable method and deserves future attention.

PMID- 25562732
TI  - Ultrasensitive simultaneous detection of four biomarkers based on hybridization
      chain reaction and biotin-streptavidin signal amplification strategy.
AB  - A sandwich-type electrochemical immunosensor based on redox probe tags
      identification technology for ultrasensitive simultaneous detection of four
      antigens was proposed. In this project, well-distributed graphene/gold (GR-Au)
      hybrid film was acquired through one-step codeposition in an electrode surface
      and served as the base substrate for immobilizing capture antibodies (Ab1).
      Hybridization chain reaction (HCR) and biotin/streptavidin (B/SA), combining with
      gold magnetic nanoparticles were applied to increase the immobilization amount of
      signal tags in detection antibody (Ab2) bioconjugates. To verify this strategy,
      four representative biomarkers, a-fetoprotein (AFP), carcinoembryonic antigen
      (CEA), carbohydrate antigen (CA)125 and prostate special antigen (PSA), were used
      as model analytes. The resulting immunosensor could simultaneously detect four
      antigens in single-pass differential pulse voltammetry (DPV) scan, and exhibited
      obviously improved senstivity compared to previous similar immunosensors,
      displayed good linear relationships in the ranges from 0.2 to 800 pg/mL for AFP,
      0.2 to 600 pg/mL for CEA, 0.2 to 1000 pg/mL for CA125, 0.2 to 800 pg/mL for PSA
      and with detection limits of 62, 48, 77 and 60 fg/mL, respectively.

PMID- 25562731
TI  - Cronobacter sakazakii: stress survival and virulence potential in an
      opportunistic foodborne pathogen.
AB  - A characteristic feature of the opportunistic foodborne pathogen Cronobacter
      sakazakii is its ability to survive in extremely arid environments, such as
      powdered infant formula, making it a dangerous opportunistic pathogen of
      individuals of all age groups, especially infants and neonates. Herein, we
      provide a brief overview of the pathogen; clinical manifestations, environmental
      reservoirs and our current understanding of stress response mechanisms and
      virulence factors which allow it to cause disease. 

PMID- 25562733
TI  - Self-enhanced electrochemiluminescence immunosensor based on nanowires obtained
      by a green approach.
AB  - Co-reactant electrochemiluminescence (ECL) is a simple and effective method for
      sensitive detection with amplified ECL signals. However, the intermolecular
      interaction between the luminescent reagents and their corresponding co
      reactants, which is widely applied, has disadvantages in poor stability, low
      efficiency of electron transfer and relatively high loss of energy. In this work,
      an intramolecular self-enhanced ECL is proposed to settle this problem. Firstly,
      palladium nanowires (PdNWs) are synthesized with a green procedure in which
      Lentinan (LNT), one of beta-glucans with a triple helical conformation (t-LNT) in
      aqueous solution and single chains (s-LNT) at a temperature higher than 130
      degrees C, is used as stabilizer and reducing agent. The abtined PdNWs are
      applied to immobilize polyamidoamine (PAMAM) dendrimer which further reacts with
      tris (4, 4'-dicarboxylicacid-2, 2'-bipyridyl) ruthenium (II) dichloride to form a
      new electrochemiluminescent derivative (PdNWs-PAMAM-Ru). In this way, the Ru (II)
      luminophore and its co-reactive groups (amine groups in PAMAM) exist in the same
      complex, by which the electronic transmission distance is shortened and the
      luminous properties including stability and efficiency are enhanced. Moreover,
      due to the high specific surface areas and good electro-catalytic ability of
      PdNWs, the obtained PdNWs-PAMAM-Ru can be also applied to immobilize detection
      antibody (Ab2). Then, a sandwiched and sensitive ECL immunosensor is fabricated
      for the detection of carcinoembryonic antigen (CEA) with a wide linear ranged
      from 0.001 ng mL(-1) to 80 ng mL(-1) and a low detection limit of 0.3 pg mL(-1).

PMID- 25562734
TI  - A highly sensitive and specific electrochemical sensing method for robust
      detection of Escherichia coli lac Z gene sequence.
AB  - Based on the interaction mode of capture probe-target-signal probe (CP-T-SP), a
      simple but efficient electrochemical sensing method is developed for robust
      detection of Escherichia coli (E. coli) lac Z gene sequence. The sensing system
      is simply composed of two probes with CP attached to the surface of gold
      electrode and methylene blue (MB)-labeled SP free in the detecting solution. Two
      duplexes are formed with the target DNA, an E. coli lac Z gene sequence,
      hybridizing with two ends of CP and SP separately. This structure can position
      the MB labels near to the electrode surface, thereby resulting in the change of
      detecting current. The proposed sensor exhibits a high sensitivity with a
      detection limit of ~30 fM for target DNA and good mismatch discrimination ability
      (MDA). This method can also be applied to the construction of other sensors for
      the analysis of similar designated pathogenic bacteria gene sequence (PBGS).

PMID- 25562735
TI  - Electrochemical sensing of microRNAs: avenues and paradigms.
AB  - Twenty years has passed since the first discovery of microRNA (miRNA) lin-4 in
      Caenorhabditis elegans. Over the last two decades, the study of miRNAs has
      attracted tremendous attention. These new stars of biomarkers are naturally
      occurring non-coding RNAs that regulate gene expression posttranscriptionally and
      have been demonstrated to be dysregulated in many diseases. Since their profiles
      reflect pathological conditions, miRNAs have recently been proposed as biomarkers
      of the onset, prognosis and risk of diseases, as well as in the classification of
      different types of cancer. The establishment of miRNA profiles for diseases and
      the detection of different types and levels of miRNAs in biological samples are
      therefore critical milestones in diagnostics. This provides powerful impetus and
      a growing demand for researchers to develop simple analytical techniques to allow
      for an accurate, sensitive, selective, and cost effective miRNA analysis at point
      of-care settings. Among several methods proposed for miRNA detection,
      electrochemical nucleic acid biosensors exhibit many attractive features and
      could play a leading role in future miRNA detection and quantification. This
      review gives an overview of recent advances in the rapidly growing area of
      electrochemical detection of miRNAs. The fundamentals of the different strategies
      adopted for miRNA detection are discussed and some examples of relevant
      approaches are highlighted, along with future prospects and challenges. 

PMID- 25562736
TI  - Nanomaterial-based cocaine aptasensors.
AB  - Up to now, many different methods have been developed for detection of cocaine,
      but most of these methods are usually time-consuming, tedious and require special
      or expensive equipment. Therefore, the development of simple, sensitive and rapid
      detection methods is necessary. In the last decade, aptamers have been used as a
      new biosensor platform for detection of cocaine in different samples. Aptamers
      are artificial single-stranded DNA or RNA oligonucleotides capable of binding to
      specific molecular targets with high affinity and if integrated to nanomaterials,
      it may lead in precise methods for cocaine detection in the common laboratories.
      In this review, recent advances and applications of aptamer-based biosensors and
      nanobiosensors, have been updated, paying attention to the use of fluorescence,
      colorimetric and electrochemical techniques for the detection and quantitative
      determination of cocaine. 

PMID- 25562737
TI  - Gelsolin bound beta-amyloid peptides(1-40/1-42): electrochemical evaluation of
      levels of soluble peptide associated with Alzheimer's disease.
AB  - A method for the highly sensitive determination of soluable beta-amyloid peptides
      (Abeta(1-40/1-42)) that employs a detection bioconjugate of HRP-Au-gelsolin as
      the electrochemical nanoprobe is presented. Contrary to previous detection
      notions that utilized antibodies, which could specifically recognize the N- or C
      terminus of peptides, we demonstrate herein that the reported specific binding
      between gelsolin and Abeta might provide an alternative way to evaluate the
      peptides sensitively and selectively. The HRP-Au-gelsolin nanohybrid was designed
      by one-pot functionalization of Au nanaoparticles (NPs) with horseradish
      peroxidase (HRP) and gelsolin. Through a sandwich-type sensor array, soluble
      Abeta(1-40/1-42) were captured onto the array due to the interactions between
      targeted peptides and surface-confined gelsolin and electrochemical signals were
      amplified by abundant attachments of HRP labeled on AuNPs, which could
      specifically catalyse its substrate, 3,3',5,5'-tetramethylbenzidine (TMB) in the
      presence of H2O2 to give rise to measurable signals. The proposed gelsolin-bound
      Abeta methodology displayed satisfactory sensitivity and wide linear range
      towards Abeta(1-40/1-42) with a detection limit down to 28 pM, which are verified
      to be sensitive-enough for the assessment of Abeta levels both in normal and
      Alzheimer's disease (AD) rat brains. Experimental results indicated that compared
      with normal group, soluble beta-amyloid peptide levels in cerebrospinal fluid
      (CSF) and targeted brain tissues of AD rats all declined with differentiable
      degrees. In short, the newly unfolding strategy presents valuable information
      related to pathological events in brain and will exhibit a braw perspective for
      the early diagnosis of AD process.

PMID- 25562738
TI  - Attomolar quantitation of Mycobacterium tuberculosis by asymmetric helicase
      dependent isothermal DNA-amplification and electrochemical detection.
AB  - A highly sensitive and robust method for the quantification of specific DNA
      sequences based on coupling asymmetric helicase-dependent DNA amplification to
      electrochemical detection is described. This method relies on the entrapment of
      the amplified ssDNA sequences on magnetic beads followed by a post-amplification
      hybridization assay to provide an added degree of specificity. As a proof-of
      concept a 84-bases long sequence specific of Mycobacterium tuberculosis is
      amplified at 65 degrees C, providing 3*10(6) amplification after 90 min. Using
      this system 0.5 aM, corresponding to 15 copies of the target gene in 50 uL of
      sample, can be successfully detected and reliably quantified under isothermal
      conditions in less than 4h. The assay has been applied to the detection of M.
      tuberculosis in sputum, pleural fluid and urine samples. Besides this
      application, the proposed assays is a powerful and general tool for molecular
      diagnostic that can be applied to the detection of other specific DNA sequences,
      taking full advantage of the plethora of genomic information now available.

PMID- 25562739
TI  - A regenerating ultrasensitive electrochemical impedance immunosensor for the
      detection of adenovirus.
AB  - We report on the development of a regenerable sensitive immunosensor based on
      electrochemical impedance spectroscopy for the detection of type 5 adenovirus.
      The multi-layered immunosensor fabrication involved successive modification steps
      on gold electrodes: (i) modification with self-assembled layer of 1,6
      hexanedithiol to which gold nanoparticles were attached via the distal thiol
      groups, (ii) formation of self-assembled monolayer of 11-mercaptoundecanoic acid
      onto the gold nanoparticles, (iii) covalent immobilization of monoclonal anti
      adenovirus 5 antibody, with EDC/NHS coupling reaction on the nanoparticles,
      completing the immunosensor. The immunosensor displayed a very good detection
      limit of 30 virus particles/ml and a wide linear dynamic range of 10(5). An
      electrochemical reductive desorption technique was employed to completely desorb
      the components of the immunosensor surface, then re-assemble the sensing layer
      and reuse the sensor. On a single electrode, the multi-layered immunosensor could
      be assembled and disassembled at least 30 times with 87% of the original signal
      intact. The changes of electrode behavior after each assembly and desorption
      processes were investigated by cyclic voltammetry, electrochemical impedance
      spectroscopy and X-ray photoelectron spectroscopy techniques. 

PMID- 25562740
TI  - Electricity production from Azo dye wastewater using a microbial fuel cell
      coupled constructed wetland operating under different operating conditions.
AB  - Microbial fuel cells (MFCs) have got tremendous attention for their capability to
      enhance the degradation of some recalcitrant pollutants and simultaneous
      electricity production. A microbial fuel cell coupled constructed wetland (CW
      MFC) is a new device to treat the wastewater and produce energy which has more
      wastewater treatment volume and more easily to maintenance than others MFCs. The
      studies on the performance of CW-MFCs are necessary. In this work, the effects of
      hydraulic residence time (HRT), reactive brilliant red X-3B (ABRX3) proportion
      and COD concentration on the electricity production of CW-MFC and the degradation
      characteristics of ABRX3 were investigated. The decolorization rate and the
      electricity production increased to a peak before slowing down with the
      elongation of HRT. The highest decolorization rate and electricity production
      were obtained when HRT was 3 days. The ABRX3 proportion (calculated as COD) in
      the wastewater played an important role in decolorization and electricity
      production, which may influence the distribution of electrons in the system. The
      power density of CW-MFC and the decolorization rate decreased concomitantly with
      an increasing ABRX3 proportion. The COD concentration influenced the CW-MFC
      performance slightly. The highest decolorization rate and power density reached
      95.6% and 0.852 W/m(3), respectively, when the COD concentration was 300 mg/L
      while the ABRX3 proportion was 30%. The coulombic efficiency of the CW-MFC
      depended on glucose and ABRX3 proportions in the wastewater. ABRX3 acquired more
      electrons than the anode. Further investigations are needed to optimize CW-MFC
      performance and explain the mechanism of biorefractory compounds degradation and
      electron motion in CW-MFCs.

PMID- 25562741
TI  - Contact lens biofuel cell tested in a synthetic tear solution.
AB  - A contact lens biofuel cell was fabricated using buckypaper electrodes cured on a
      silicone elastomer soft contact lens. The buckypaper anode consisted of
      poly(methylene green) and a hydrogel matrix containing lactate dehydrogenase and
      nicotinamide adenine dinucleotide hydrate (NAD(+)). The buckypaper cathode was
      modified with 1-pyrenemethyl anthracene-2-carboxylate, and then bilirubin oxidase
      was immobilized within a polymer. Contact lens biofuel cell testing was performed
      in a synthetic tear solution at 35 degrees C. The open circuit voltage was
      0.413+/-0.06 V and the maximum current and power density were 61.3+/-2.9 uA cm(
      2) and 8.01+/-1.4 uWc m(-2), respectively. Continuous operation for 17h revealed
      anode instability as output current rapidly decreased in the first 4h and then
      stabilized for the next 13 h. The contact lens biofuel cell presented here is a
      step toward achieving self-powered electronic contact lenses and ocular devices
      with an integrated power source.

PMID- 25562742
TI  - Aptamer-conjugated silver nanoparticles for electrochemical dual-aptamer-based
      sandwich detection of staphylococcus aureus.
AB  - Staphylococcus aureus (S. aureus) is one of the most important human pathogens
      and causes numerous illnesses. In this study, we report a sensitive and highly
      selective dual-aptamer-based sandwich immunosensor for the detection of S.
      aureus. In this bioassay system, a biotinylated primary anti-S.aureus aptamer was
      immobilized on streptavidin coated magnetic beads (MB), which serves as a capture
      probe. A secondary anti-S.aureus aptamer was conjugated to silver nanoparticles
      (Apt-AgNP) that sensitively reports the detection of the target. In the presence
      of target bacterium, an Apt/S.aureus/apt-AgNP sandwich complex is formed on the
      MB surface and the electrochemical signal of AgNPs followed through anodic
      stripping voltammetry. The proposed sandwich assay benefits from advantageous of
      a sandwich assay for increased specificity, MB as carriers of affinity ligands
      for solution-phase recognition and fast magnetic separation, AgNPs for signal
      amplification, and an electrochemical stripping voltammetry read-out as a simple
      and sensitive detection. The electrochemical immunosensor shows an extended
      dynamic range from 10 to 1*10(6) cfu/mL with a low detection limit of 1.0 cfu/mL
      (S/N=3). Furthermore, the possible interference of other analog bacteria was
      studied. To assess the general applicability of this sensor, we investigated the
      quantification of S. aureus in real water samples. The results were compared to
      the experimental results obtained from a plate counting method, which
      demonstrated an acceptable consistency.

PMID- 25562743
TI  - Simultaneous quantitative detection of multiple tumor markers with a rapid and
      sensitive multicolor quantum dots based immunochromatographic test strip.
AB  - A novel multicolor quantum dots (QDs) based immunochromatographic test strip
      (ICTS) was developed for simultaneous quantitative detection of multiple tumor
      markers, by utilizing alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA)
      as models. The immunosensor could realize simultaneous quantitative detection of
      tumor markers with only one test line and one control line on the nitrocellulose
      membrane (NC membrane) due to the introduction of multicolor QDs. In this method,
      a mixture of mouse anti-AFP McAb and mouse anti-CEA McAb was coated on NC
      membrane as test line and goat anti-mouse IgG antibody was coated as control
      line. Anti-AFP McAb-QDs546 conjugates and anti-CEA McAb-QDs620 conjugates were
      mixed and applied to the conjugate pad. Simultaneous quantitative detection of
      multiple tumor markers was achieved by detecting the fluorescence intensity of
      captured QDs labels on test line and control line using a test strip reader.
      Under the optimum conditions, AFP and CEA could be detected as low as 3 ng/mL and
      2 ng/mL in 15 min with a sample volume of 80 MUL, and no obvious cross-reactivity
      was observed. The immunosensor was validated with 130 clinical samples and in
      which it exhibited high sensitivity (93% for AFP and 87% for CEA) and specificity
      (94% for AFP and 97% for CEA). The immunosensor also demonstrated high recoveries
      (87.5-113% for AFP and 90-97.3% for CEA) and low relative standard deviations
      (RSDs) (2.8-6.2% for AFP and 4.9-9.6% for CEA) when testing spiked human serum.
      This novel multicolor QDs based ICTS provides an easy and rapid, simultaneous
      quantitative detecting strategy for point-of-care testing of tumor markers.

PMID- 25562744
TI  - Graphene oxide nanoribbon-based sensors for the simultaneous bio-electrochemical
      enantiomeric resolution and analysis of amino acid biomarkers.
AB  - In this work, a straightforward in-situ measurement of L and D-amino acids (AAs)
      has been developed using disposable graphene oxide nanoribbon (GON) screen
      printed electrodes. For that, we took advantage of the electroactivity of certain
      clinically relevant AAs, such as tyrosine (Tyr) and methionine (Met), which are
      involved in important bacterial diseases (Bacillus subtilis and Vibrio cholera,
      respectively). The strategy is based on a dual electrochemical and enzymatic
      approach. The D-AA with the class enzyme D amino acid oxidase (DAAO) generates
      H2O2. This H2O2 is simultaneously detected with the L-AA, electroactive molecule
      by differential pulse voltammetry (DPV). These GON disposable platforms use just
      50 MUL of sample and a total analysis time of 360 s. Both L and D enantiomers
      calibration and quantitative analysis were explored and were simultaneously
      detected with accuracy and precision in urine samples. Any interference of uric
      acid and other electroactive AAs was noticed. This proposed electrochemical GON
      based enantiomeric bio-sensor becomes a highly promising tool as future point of
      care for fast and reliable early diagnosis of diseases related to the presence of
      D-AAs.

PMID- 25562746
TI  - An invisible acoustic sensor based on parity-time symmetry.
AB  - Sensing an incoming signal is typically associated with absorbing a portion of
      its energy, inherently perturbing the measurement and creating reflections and
      shadows. Here, in contrast, we demonstrate a non-invasive, shadow-free, invisible
      sensor for airborne sound waves at audible frequencies, which fully absorbs the
      impinging signal, without at the same time perturbing its own measurement or
      creating a shadow. This unique sensing device is based on the unusual scattering
      properties of a parity-time (PT) symmetric metamaterial device formed by a pair
      of electro-acoustic resonators loaded with suitably tailored non-Foster
      electrical circuits, constituting the acoustic equivalent of a coherent perfect
      absorber coupled to a coherent laser. Beyond the specific application to non
      invasive sensing, our work broadly demonstrates the unique relevance of PT
      symmetric metamaterials for acoustics, loss compensation and extraordinary wave
      manipulation. 

PMID- 25562747
TI  - Applications of flow cytometry for measurement of autophagy.
AB  - Autophagy is a dynamic catabolic process that plays a major role in sequestering
      and recycling cellular components in multiple physiological and
      pathophysiological conditions. Despite recent progress in our understanding of
      the autophagic process there is still a shortage of robust methods for monitoring
      autophagy in live cells. Flow cytometry, a reliable and unbiased method for
      quantitative collection of data in a high-throughput manner, was recently
      utilized to monitor autophagic activity in live and fixed mammalian cells. In
      this article we summarize the advantages and potential pitfalls of the use of
      flow cytometry to study autophagy. 

PMID- 25562745
TI  - Cancer-type-specific crosstalk between autophagy, necroptosis and apoptosis as a
      pharmacological target.
AB  - Cell death plays an essential role in the development of organs, homeostasis, and
      cancer. Apoptosis and programmed necrosis are two major types of cell death,
      characterized by different cell morphology and pathways. Accumulating evidence
      shows autophagy as a new alternative target to treat tumor resistance. Besides
      its well-known pro-survival role, autophagy can be a physiological cell death
      process linking apoptosis and programmed necrosis cell death pathways, by various
      molecular mediators. Here, we summarize the effects of pharmacologically active
      compounds as modulators of different types of cancer cell death depending on the
      cellular context. Indeed, current findings show that both natural and synthetic
      compounds regulate the interplay between apoptosis, autophagy and necroptosis
      stimulating common molecular mediators and sharing common organelles. In response
      to specific stimuli, the same death signal can cause cells to switch from one
      cell death modality to another depending on the cellular setting. The discovery
      of important interconnections between the different cell death mediators and
      signaling pathways, regulated by pharmacologically active compounds, presents
      novel opportunities for the targeted treatment of cancer. The aim of this review
      is to highlight the potential role of these compounds for context-specific
      anticancer therapy. 

PMID- 25562748
TI  - Immunohistochemical assessment of PTEN in vulvar cancer: best practices for
      tissue staining, evaluation, and clinical association.
AB  - BACKGROUND: Pten encodes a well-characterized protein that is important in
      several cancers due to its tumor suppressor function. Yet, the detection and
      evaluation of PTEN by immunohistochemistry (IHC) for clinical practice have not
      been standardized. Thus, in this study, we performed a literature review of
      protocols for PTEN assessment by IHC and the possible differences in evaluation,
      based on our experience with vulvar carcinomas. Also, we report some of our most
      recent findings regarding the clinical impact of PTEN in this type of tumor.
      METHODS: In total, 150 FFPE vulvar carcinoma samples in a tissue microarray were
      examined by IHC with regard to PTEN, PI3K, AKT, and mTOR. All evaluations were
      performed by slide digitalization and quantification using APERIO ImageScope
      software. All measurements were converted into HScore values for the statistical
      analysis. RESULTS: Sharp and specific PTEN expression was observed in the nuclei
      and cytoplasmic compartments. Its HScore values ranged from 3.5 to 226, with a
      median of 92.5. mTOR expression was robust in all cases (mean HScore=248.1). AKT
      and PI3K had median HScore values of 200.5 and 156.5, respectively. In addition,
      PTEN expression was associated with higher rates of patient survival. CONCLUSION:
      The preanalytical step is the first issue in the immunohistochemical evaluation
      of PTEN. With regard to the analytical procedure, the antigen retrieval step
      yielded better stains for protocols with high-pH buffers, and antibody clone
      6H2.1 effected the most reliable results. PTEN is a good prognostic marker for
      vulvar cancer, correlating with higher rates of patient survival. Our data
      underscore the importance of technical standardization to ensure more reliable
      and reproducible evaluation of PTEN in clinical practice.

PMID- 25562749
TI  - Uncertainty as an anxiety cue at high and low levels of threat.
AB  - BACKGROUND AND OBJECTIVES: Intolerance of uncertainty and the overestimation of
      threat contribute to the maintenance of anxiety; however, the interaction between
      uncertainty and threat perception has not been examined empirically. The current
      study examined the extent to which explicitness of uncertainty is involved in
      perceptions of, and responses to, scenarios about threatening situations.
      METHODS: A series of systematically varied scenarios were used to examine whether
      manipulating uncertainty (implicit vs. explicit) and threat level (high vs. low)
      altered the perception of a situation as anxiety-inducing. Undergraduate
      participants (n = 373) responded to vignettes about common situations (e.g.,
      taking an elevator) with ratings of anxiety and desire to perform a safety
      behavior. RESULTS: Results revealed that higher threat situations, and those in
      which uncertainty was made explicit, provoked higher ratings of anxiety and urge
      to perform a safety behavior. In addition, explicit uncertainty significantly
      increased anxiety and urge to perform a safety behavior at low, but not at high,
      levels of threat. LIMITATIONS: Participants rated (via self-report) their
      hypothetical feelings as induced by vignettes, rather than actually experiencing
      these situations in vivo. CONCLUSIONS: We found evidence for "uncertainty-based
      reasoning," in which an individual perceives a situation as more anxiety
      provoking (and is more likely to have the urge to perform a safety behavior) when
      the uncertain aspects of a situation are obvious or explicit, than when such
      uncertainty is merely implied or tacit. Implications for the understanding of
      "uncertainty-based reasoning" are discussed.

PMID- 25562750
TI  - Protocol-directed sedation versus non-protocol-directed sedation to reduce
      duration of mechanical ventilation in mechanically ventilated intensive care
      patients.
AB  - BACKGROUND: The sedation needs of critically ill patients have been recognized as
      a core component of critical care and meeting these is vital to assist recovery
      and ensure humane treatment. There is growing evidence to suggest that sedation
      requirements are not always optimally managed. Sub-optimal sedation incorporates
      both under- and over-sedation and has been linked to both short-term (e.g. length
      of stay) and long-term (e.g. psychological recovery) outcomes. Various strategies
      have been proposed to improve sedation management and address aspects of
      assessment as well as delivery of sedation. OBJECTIVES: To assess the effects of
      protocol-directed sedation management on the duration of mechanical ventilation
      and other relevant patient outcomes in mechanically ventilated intensive care
      unit (ICU) patients. We looked at various outcomes and examined the role of bias
      in order to examine the level of evidence for this intervention. SEARCH METHODS:
      We searched the Cochrane Central Register of Controlled trials (CENTRAL) (2013;
      Issue 11), MEDLINE (OvidSP) (1990 to November 2013), EMBASE (OvidSP) (1990 to
      November 2013), CINAHL (BIREME host) (1990 to November 2013), Database of
      Abstracts of Reviews of Effects (DARE) (1990 to November 2013), LILACS (1990 to
      November 2013), Current Controlled Trials and US National Institutes of Health
      Clinical Research Studies (1990 to November 2013), and reference lists of
      articles. We re-ran the search in October 2014. We will deal with any studies of
      interest when we update the review. SELECTION CRITERIA: We included randomized
      controlled trials (RCTs) conducted in adult ICUs comparing management with and
      without protocol-directed sedation. DATA COLLECTION AND ANALYSIS: Two authors
      screened the titles and abstracts and then the full-text reports identified from
      our electronic search. We assessed seven domains of potential risk of bias for
      the included studies. We examined the clinical, methodological and statistical
      heterogeneity and used the random-effects model for meta-analysis where we
      considered it appropriate. We calculated the mean difference (MD) for duration of
      mechanical ventilation and risk ratio (RR) for mortality across studies, with 95%
      confidence intervals (CI). MAIN RESULTS: We identified two eligible studies with
      633 participants. Both included studies compared the use of protocol-directed
      sedation, specifically protocols delivered by nurses, with usual care. We rated
      the risk of selection bias due to random sequence generation low for one study
      and unclear for one study. The risk of selection bias related to allocation
      concealment was low for both studies. We also assessed detection and attrition
      bias as low for both studies while we considered performance bias high due to the
      inability to blind participants and clinicians in both studies. Risk due to other
      sources of bias, such as potential for contamination between groups and reporting
      bias, was considered unclear. There was no clear evidence of differences in
      duration of mechanical ventilation (MD -5.74 hours, 95% CI -62.01 to 50.53, low
      quality evidence), ICU length of stay (MD -0.62 days, 95% CI -2.97 to 1.73) and
      hospital length of stay (MD -3.78 days, 95% CI -8.54 to 0.97) between people
      being managed with protocol-directed sedation versus usual care. Similarly, there
      was no clear evidence of difference in hospital mortality between the two groups
      (RR 0.96, 95% CI 0.71 to 1.31, low quality evidence). ICU mortality was only
      reported in one study preventing pooling of data. There was no clear evidence of
      difference in the incidence of tracheostomy (RR 0.77, 95% CI 0.31 to 1.89). The
      studies reported few adverse event outcomes; one study reported self extubation
      while the other study reported re-intubation; given this difference in outcomes,
      pooling of data was not possible. There was significant heterogeneity between
      studies for duration of mechanical ventilation (I(2) = 86%, P value = 0.008), ICU
      length of stay (I(2) = 82%, P value = 0.02) and incidence of tracheostomy (I(2) =
      76%, P value = 0.04), with one study finding a reduction in duration of
      mechanical ventilation and incidence of tracheostomy and the other study finding
      no difference. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to
      evaluate the effectiveness of protocol-directed sedation. Results from the two
      RCTs were conflicting, resulting in the quality of the body of evidence as a
      whole being assessed as low. Further studies, taking into account contextual and
      clinician characteristics in different ICU environments, are necessary to inform
      future practice. Methodological strategies to reduce the risk of bias need to be
      considered in future studies.

PMID- 25562751
TI  - Measurement of enhanced radium isotopes in oil production wastes in Turkey.
AB  - Gamma dose rates of oil production equipment and wastes were measured externally
      by survey meter. They were found to be between 0.2 MUSv h(-1) and 25.7 MUSv h(
      1). Activity concentrations of radium isotopes in crude oil, scale, sludge,
      contaminated soil and water samples were determined by gamma spectrometric
      method. Activity concentrations of (224)Ra, (226)Ra and (228)Ra in samples varied
      from MDA to 132,000 Bq kg(-1). Radium isotopes enriched up to 14,667 times in
      scale samples. The highest value of (226)Ra was found to be 35,122 +/- 1,983 Bq
      kg(-1) for sludge samples. Activity concentrations of a considerable number of
      samples were found to be higher than the exemption level recommended by IAEA.
      Measurement results revealed that oil production wastes caused soil contamination
      up to 70,483 Bq kg(-1). They may pose a radiological risk for workers and members
      of the public.

PMID- 25562752
TI  - Plutonium(IV) sorption to montmorillonite in the presence of organic matter.
AB  - The effect of altering the order of addition in a ternary system of
      plutonium(IV), organic matter (fulvic acid, humic acid and desferrioxamine B),
      and montmorillonite was investigated. A decrease in Pu(IV) sorption to
      montmorillonite in the presence of fulvic and humic acid relative to the binary
      Pu-montmorillonite system, is attributed to strong organic aqueous complex
      formation with aqueous Pu(IV). No dependence on the order of addition was
      observed. In contrast, in the system where Pu(IV) was equilibrated with
      desferrioxamine B (DFOB) prior to addition of montmorillonite, an increase in
      Pu(IV) sorption was observed relative to the binary system. When DFOB was
      equilibrated with montmorillonite prior to addition of Pu(IV), Pu(IV) sorption
      was equivalent to the binary system. X-ray diffraction and transmission electron
      microscopy revealed that DFOB accumulated in the interlayer of montmorillonite.
      The order of DFOB addition plays an important role in the observed
      sorption/desorption behavior of Pu. The irreversible nature of DFOB accumulation
      in the montmorillonite interlayer leads to an apparent dependence of Pu sorption
      on the order of addition in the ternary system. This work demonstrates that the
      order of addition will be relevant in ternary systems in which at least one
      component exhibits irreversible sorption behavior. 

PMID- 25562753
TI  - Polymorphic CoSe2 with mixed orthorhombic and cubic phases for highly efficient
      hydrogen evolution reaction.
AB  - We report polymorphic CoSe2 (p-CoSe2) with mixed orthorhombic and cubic phases as
      a highly active electrocatalyst toward hydrogen evolution reaction (HER). The p
      CoSe2 is obtained by calcining CoSex via electrodeposition at 300  degrees C. The
      results of X-ray diffraction (XRD) and high-resolution transmission electron
      microscopy (HRTEM) demonstrated the crystal structure of p-CoSe2. The p-CoSe2
      exhibits excellent electrocatalytic activity for HER with a low onset
      overpotential of -70 mV and a small Tafel slope of ~30 mV/decade, which are
      basically state-of-the-art performance of earth-abundant electrocatalysts. The
      HER performance of p-CoSe2 was much higher than that of amorphous CoSex, cubic
      CoSe2, and CoSe. This study offers a competitive electrocatalyst for HER and
      opens up a new strategy to the synthesis of catalysts for energy conversion. 

PMID- 25562754
TI  - Physically active lessons as physical activity and educational interventions: a
      systematic review of methods and results.
AB  - OBJECTIVE: Physically active lessons aim to increase children's physical activity
      whilst maintaining academic time. This systematic review aimed to investigate the
      methods used in such interventions and their effects on physical activity and
      educational outcomes. METHODS: In March 2014; PubMed, Web of Science, PsycINFO
      and ERIC electronic databases were searched. Inclusion criteria were: 1.
      Classroom lessons containing both PA and educational elements; 2. intervention
      studies featuring a control group or within-subjects baseline measurement period;
      3. any age-group; and 4. English language. Studies assessing physically active
      lessons within complex interventions were excluded. Data were extracted onto a
      standardised form. Risk of bias was assessed using the Effective Public Health
      Practice Project (EPHPP) tool. RESULTS: Eleven studies were identified: five
      examined physical activity outcomes only, three examined educational outcomes
      only and three examined both physical activity and educational outcomes. All
      studies found improved physical activity following physically active lessons:
      either in the whole intervention group or in specific demographics. Educational
      outcomes either significantly improved or were no different compared to inactive
      teaching. Studies ranged from low to high risk of bias. CONCLUSIONS: Encouraging
      evidence of improved physical activity and educational outcomes following
      physically active lessons is provided. However, too few studies exist to draw
      firm conclusions. Future high-quality studies with longer intervention periods
      are warranted.

PMID- 25562755
TI  - Borrowing from tobacco control to curtail the overweight and obesity epidemic:
      Leveraging the U.S. Surgeon General's Report.
AB  - There is broad agreement that more needs to be done to curtail the U.S.
      overweight and obesity epidemic. Fifty years of regular Surgeon General's Reports
      on the health consequences of smoking appear to have been a highly effective
      contributor to the notable successes that have been made in reducing smoking
      prevalence. Comparing the rate of Surgeon General's Reports on smoking and
      obesity reveals striking differences, with more than a five-fold lower rate of
      reporting on the latter. Developing practices that more effectively leverage the
      power of the U.S. Surgeon General's Office in efforts to reduce obesity is a
      relatively straightforward but potentially powerful additional step that warrants
      consideration. 

PMID- 25562756
TI  - Does social support mediate the relationship among neighborhood disadvantage,
      incivilities, crime and physical activity?
AB  - OBJECTIVE: Neighborhood disadvantage (ND), incivilities, and crime
      disproportionately impact minority women, discouraging physical activity (PA).
      Social support (SS) is a cultural tool promoting PA in minority women. Socially
      supportive environments may promote PA in disadvantaged neighborhoods, yet few
      studies have investigated the mediating role of social support among minority
      women. This study examined SS as a mediator among ND, incivilities, crime, and
      PA. METHODS: The Health Is Power study aimed to increase PA in African American
      and Hispanic Latina women (N=410) in Houston and Austin, TX. ND and crime data
      were taken from the National Neighborhood Crime Study. Incivilities were measured
      using the Pedestrian Environment Data Scan (PEDS). SS was measured using the
      Family and Friend Support for Exercise Habits scale and physical activity was
      measured using the International Physical Activity Questionnaire. Linear
      regression analysis was used to examine SS as a mediator following the Baron and
      Kenny method. RESULTS: ND was negatively associated with PA and SS. SS was not a
      mediator as it was not significantly associated with ND, crime, and incivilities
      (F(3,264)=2.02, p>.05) or PA (F(1,266)=3.8 p=.052). CONCLUSION: ND significantly
      discourages PA and limits SS. Future research should focus on developing
      strategies to overcoming these negative environmental factors.

PMID- 25562757
TI  - Role of Ctf3 and COMA subcomplexes in meiosis: Implication in maintaining Cse4 at
      the centromere and numeric spindle poles.
AB  - During mitosis and meiosis, kinetochore, a conserved multi-protein complex,
      connects microtubule with the centromere and promotes segregation of the
      chromosomes. In budding yeast, central kinetochore complex named Ctf19 has been
      implicated in various functions and is believed to be made up of three
      biochemically distinct subcomplexes: COMA, Ctf3 and Iml3-Chl4. In this study, we
      aimed to identify whether Ctf3 and COMA subcomplexes have any unshared function
      at the kinetochore. Our data suggests that both these subcomplexes may work as a
      single functional unit without any unique functions, which we tested. Analysis of
      severity of the defects in the mutants suggests that COMA is epistatic to Ctf3
      subcomplex. Interestingly, we noticed that these subcomplexes affect the
      organization of mitotic and meiotic kinetochores with subtle differences and they
      promote maintenance of Cse4 at the centromeres specifically during meiosis which
      is similar to the role of Mis6 (Ctf3 homolog) in fission yeast during mitosis.
      Interestingly, analysis of ctf3Delta and ctf19Delta mutants revealed a novel role
      of Ctf19 complex in regulation of SPB cohesion and duplication in meiosis. 

PMID- 25562758
TI  - Impact of screw configuration on the particle size distribution of granules
      produced by twin screw granulation.
AB  - Twin screw granulation (TSG) has been reported by different research groups as an
      attractive technology for continuous wet granulation. However, in contrast to
      fluidized bed granulation, granules produced via this technique typically have a
      wide and multimodal particle size distribution (PSD), resulting in suboptimal
      flow properties. The aim of the current study was to evaluate the impact of
      granulator screw configuration on the PSD of granules produced by TSG.
      Experiments were performed using a 25 mm co-rotating twin screw granulator, being
      part of the ConsiGmaTM-25 system (a fully continuous from-powder-to-tablet
      manufacturing line from GEA Pharma Systems). Besides the screw elements
      conventionally used for TSG (conveying and kneading elements), alternative
      designs of screw elements (tooth-mixing-elements (TME), screw mixing elements
      (SME) and cutters) were investigated using an alpha-lactose monohydrate
      formulation granulated with distilled water. Granulation with only conveying
      elements resulted in wide and multimodal PSD. Using kneading elements, the width
      of the PSD could be partially narrowed and the liquid distribution was more
      homogeneous. However, still a significant fraction of oversized agglomerates was
      obtained. Implementing additional kneading elements or cutters in the final
      section of the screw configuration was not beneficial. Furthermore, granulation
      with only TME or SME had limited impact on the width of the PSD. Promising
      results were obtained by combining kneading elements with SME, as for these
      configurations the PSD was narrower and shifted to the size fractions suitable
      for tableting.

PMID- 25562759
TI  - On the future of psychodynamic therapy research.
AB  - OBJECTIVE AND METHOD: Two psychodynamic therapists and researchers from different
      generations reflected upon the past and present state of psychodynamic therapy
      research as well as possibilities for the future. RESULTS AND CONCLUSIONS:
      Several issues (e.g., decreased research funding, increased medicalization of
      mental health problems, and declining psychodynamic representation among research
      faculty) were identified as potential impediments for future high-quality
      research. In addition to encouraging the field to face these challenges directly,
      a number of specific recommendations were provided. These included not only
      suggestions for traditional process and outcome research, but also
      recommendations to modify our current assessment practices, improve our field's
      cohesiveness, increase our public visibility, and improve relationships with our
      non-psychodynamic colleagues. In is argued that, if the field confronts these
      many challenges in a creative and flexible manner, psychodynamic therapy research
      will not only continue to be relevant, but will also thrive.

PMID- 25562760
TI  - Functional layer-by-layer design of xerogel-based first-generation amperometric
      glucose biosensors.
AB  - Xerogel-based first-generation amperometric glucose biosensors, constructed
      through specific layer-by-layer assembly of films featuring glucose oxidase doped
      xerogel, a diffusion-limiting xerogel layer, and capped with both
      electropolymerized polyphenol and blended polyurethane semipermeable membranes,
      are presented. The specific combination of xerogels formed from specific silane
      precursors, including propyl-trimethoxysilane, isobutyl-trimethoxysilane, octyl
      trimethoxysilane, and hydroxymethyl-triethoxysilane, exhibit impressive dynamic
      and linear ranges of detection (e.g., >=24-28 mM glucose) and low response times,
      as well as significant discrimination against common interferent species such as
      acetaminophen, ascorbic acid, sodium nitrite, oxalic acid, and uric acid as
      determined by selectivity coefficients. Additionally, systematic electrochemical
      and contact angle studies of different xerogel silane precursors, varying in
      structure, chain length, and/or functional group, reveal that sensor performance
      is more dependent on the tunable porosity/permeability of the layered interfaces
      rather than the hydrophobic character or functional groups within the films.
      While the sensing performance largely exceeds that of existing electrochemical
      glucose sensing schemes in the literature, the presented layered approach
      establishes the specific functionality of each layer working in concert with each
      other and suggests that the strategy may be readily adaptable to other clinically
      relevant targets and is amenable to miniaturization for eventual in situ or in
      vivo sensing. 

PMID- 25562761
TI  - J. Daniel Subtelny: a man of thought, action and vision.

PMID- 25562765
TI  - Hyposalinity stress compromises the fertilization of gametes more than the
      survival of coral larvae.
AB  - The life cycle of coral is affected by natural and anthropogenic perturbations
      occurring in the marine environment. In the context of global changes, it is
      likely that rainfall events will be more intense and that coastal reefs will be
      exposed to sudden drops in salinity. Therefore, a better understanding of how
      corals-especially during the pelagic life stages-are able to deal with declines
      in salinity is crucial. To fill this knowledge gap, this work investigated how
      gametes and larva stages of two species of Acropora (Acropora cytherea and
      Acropora pulchra) from French Polynesia cope with drops in salinity. An analysis
      of collected results highlights that both Acropora coral gametes displayed the
      same resistance to salinity changes, with 4h30-ES50 (effective salinity that
      decrease by 50% the fertilization success after 4h30 exposure) of 26.6 +/- 0.1
      and 27.5 +/- 0.30/00 for A. cytherea and A. pulchra, respectively. This study
      also revealed that coral gametes were more sensitive to decreases in salinity
      than larvae, for which significant changes are only observed at 260/00 for A.
      cytherea after 14 d of exposure. Although rising seawater temperatures and ocean
      acidification are often perceived as the main threat for the survival of coral
      reefs, our work indicates that 70% of the gametes could be killed during a single
      night of spawning by a rainfall event that decreases salinity to 260/00. This
      suggests that changes in the frequency and intensity of rainfall events
      associated with climate changes should be taken seriously in efforts to both
      preserve coral gametes and ensure the persistence and renewal of coral
      populations. 

PMID- 25562766
TI  - A comparative study of proteomic differences between pencil and storage roots of
      sweetpotato (Ipomoea batatas (L.) Lam.).
AB  - Fibrous roots of sweetpotato (Ipomoea batatas (L.) Lam.) usually develop into
      both pencil and storage roots. To understand protein function in root
      development, a proteomic analysis was conducted on the pencil and storage roots
      of the light orange-fleshed sweetpotato cultivar, Yulmi. Two-dimensional gel
      electrophoresis showed that expression of 30 protein spots differed between
      pencil and storage roots: 15 proteins were up-regulated or expressed in pencil
      roots and 15 in storage roots. Differentially expressed proteins spots were
      investigated using matrix-assisted laser desorption/ionization time of flight
      mass spectrometry, and 10 proteins from pencil roots were identified as binding
      protein isoform A, catechol oxidase, peroxidases, ascorbate peroxidase,
      endochitinase, flavanone 3-hydroxylase and unknown proteins. Of the proteins up
      regulated in, or restricted to, storage roots, 13 proteins were identified as
      protein disulfide isomerase, anionic peroxidase, putative ripening protein,
      sporamin B, sporamin A and sporamin A precursor. An analysis of enzyme activity
      revealed that catechol oxidase and peroxidase as the first and last enzymes of
      the lignin biosynthesis pathway, and ascorbate peroxidase had higher activities
      in pencil than in storage roots. The total concentration of phenolic compounds
      was also far higher in pencil than in storage roots, and lignin accumulated only
      in pencil roots. These results provide important insight into sweetpotato
      proteomics, and imply that lignin biosynthesis and stress-related proteins are up
      regulated or uniquely expressed in pencil roots. The results indicate that the
      reduction of carbon flow toward phenylpropanoid biosynthesis and its delivery to
      carbohydrate metabolism is a major event in storage root formation.

PMID- 25562767
TI  - The impact of air pockets around the vaginal cylinder on vaginal vault
      brachytherapy.
AB  - OBJECTIVE: To evaluate the incidence, size and predisposing factors for air
      pockets around the vaginal cylinder and their dosimetric effect on the vaginal
      mucosa. METHODS: We investigated 174 patients with endometrial carcinoma treated
      with external radiotherapy (RT) and brachytherapy (BRT) (101 patients, 58%) or
      BRT alone (73 patients, 42%). The quantity, volume and dosimetric impact of the
      air pockets surrounding the vaginal cylinder were quantified. The proportions of
      patients with or without air pockets during application were stratified according
      to menopausal status, treatment modality and interval between surgery and RT.
      RESULTS: Air pockets around the vaginal cylinder were seen in 75 patients (43%),
      while 99 patients (57%) had no air pockets. Only 11 patients (6.3%) received less
      than the prescribed dose (average 93.9% of prescribed dose; range, 79.0-99.2%).
      Air pockets were significantly fewer in pre-menopausal patients or in patients
      treated with the combination of external RT and BRT than in post-menopausal
      patients or patients treated with BRT alone. A significant correlation existed
      between the mucosal displacement of the air gap and the ratio of the measured
      dose at the surface of the air gap and prescribed dose (Pearson r = -0.775; p <
      0.001). CONCLUSION: Air pockets were still a frequent problem during vaginal
      vault BRT, especially in post-menopausal patients or in patients treated with BRT
      alone, which may potentially cause dose reductions at the vaginal mucosa.
      ADVANCES IN KNOWLEDGE: Air pockets around the vaginal cylinder remain a
      significant problem, which may potentially cause dose reduction in the target
      volume.

PMID- 25562768
TI  - Blanchfield Army Community Hospital Polypharmacy Clinic.
AB  - The increased use of central nervous system depressants (CNSD) and psychotropics
      are one of the many factors that contribute to suicidal behavior in soldiers.
      U.S. Army policy requires medication screening for any soldier prescribed 4 or
      more medications when at least 1 of the medications is a CNSD or psychotropic.
      Constant deployments challenged health care provider ability to comply with
      required screenings, and senior leaders sought proactive intervention to reduce
      medication risks upon return of the 101 st Airborne Division (Air Assault) from
      deployment in 2011. A pharmacy-led team established the Polypharmacy Clinic (PC)
      at Blanchfield Army Community Hospital. Of the 3,999 soldiers assigned, 540
      (13.5%) met the initial screening criteria. Success of the pilot program led to
      the mandatory screening of all other Fort Campbell, Kentucky, brigades. During
      the first 12 months, 895 soldiers were seen by a clinical pharmacist, and 1,574
      interventions were documented. Significant interventions included medication
      added (121), medication changed (258), medication stopped (164), lab monitoring
      recommended (172), adverse reaction mitigated (41), therapeutic duplication
      prevented (61), and drug-drug interaction identified (93). Additionally, 55
      soldiers were recommended for temporary duty profiles based on their adverse drug
      effects. Ten soldiers were recommended for enhanced controlled substance
      monitoring. Placing soldiers on clinically appropriate medications and removing
      potentially harmful medications from their possession are examples of how the PC
      positively impacted the Commanding General's ability to deploy a fully medically
      ready force. Soldiers consistently remarked favorably on the thorough medication
      counseling provided at their PC appointments. Innovative notes within the
      electronic health record summarized relevant findings regarding soldiers'
      medications, which allowed providers to quickly pinpoint and adjust medication
      regimens. With each identified high-risk soldier, we decreased the potential for
      postdeployment medication issues. Additionally, the PC generated over $70,000 in
      relative value units for the hospital.

PMID- 25562769
TI  - Motivational interviewing and specialty pharmacy.
AB  - It is well documented in substance abuse and health care literature that
      motivational interviewing is an evidenced-based and effective intervention for
      influencing patient behaviors and associated positive health outcomes. The
      introduction of motivational interviewing training in specialty pharmacy has
      great potential to increase patient and pharmacist satisfaction, maximize
      adherence rates, and improve health outcomes. This commentary examines the need
      for effective approaches for improving patient adherence and outcomes and briefly
      describes the history and efficacy of motivational interviewing. Case studies
      using traditional approaches to patient care and motivational interviewing are
      analysed, and real-world experience using motivational interviewing is presented
      in the form of a specialty pharmacy case study.

PMID- 25562770
TI  - Utilizing data consortia to monitor safety and effectiveness of biosimilars and
      their innovator products.
AB  - BACKGROUND: The Biologics Price Competition and Innovation Act, introduced as
      part of the Affordable Care Act, directed the FDA to create an approval pathway
      for biologic products shown to be biosimilar or interchangeable with an FDA
      approved innovator drug. These biosimilars will not be chemically identical to
      the reference agent. Investigational studies conducted with biosimilar agents
      will likely provide limited real-world evidence of their effectiveness and
      safety. How do we best monitor effectiveness and safety of biosimilar products
      once approved by the FDA and used more extensively by patients? OBJECTIVE: To
      determine the feasibility of developing a distributed research network that will
      use health insurance plan and health delivery system data to detect biosimilar
      safety and effectiveness signals early and be able to answer important managed
      care pharmacy questions from both the government and managed care organizations.
      METHODS: Twenty-one members of the AMCP Task Force on Biosimilar Collective
      Intelligence Systems met November 12, 2013, to discuss issues involved in
      designing this consortium and to explore next steps. RESULTS: The task force
      concluded that a managed care biosimilars research consortium would be of
      significant value. Task force members agreed that it is best to use a distributed
      research network structurally similar to existing DARTNet, HMO Research Network,
      and Mini-Sentinel consortia. However, for some surveillance projects that it
      undertakes, the task force recognizes it may need supplemental data from managed
      care and other sources (i.e., a "hybrid" structure model). CONCLUSIONS: The task
      force believes that AMCP is well positioned to lead the biosimilar-monitoring
      effort and that the next step to developing a biosimilar-innovator collective
      intelligence system is to convene an advisory council to address organizational
      governance.

PMID- 25562771
TI  - Health care costs among renal cancer patients using pazopanib and sunitinib.
AB  - BACKGROUND: Pazopanib was noninferior to sunitinib in progression-free survival
      in a phase III, open-label, randomized clinical trial comparing the efficacy and
      safety of the 2 drugs for treatment of patients with advanced renal cell
      carcinoma (RCC). A secondary analysis of this trial conducted on patient-reported
      health care resource utilization (HCRU) endpoints revealed significantly fewer
      monthly telephone consultations and emergency department visits among patients
      treated with pazopanib over the first 6 months of treatment. OBJECTIVES: To (a)
      compare total costs of HCRU and adverse events (AEs) in patients with advanced
      RCC receiving first-line pazopanib or sunitinib from the phase III clinical trial
      and (b) perform a post hoc economic analysis that applied direct medical care and
      pharmacy unit costs, obtained from the Truven Health MarketScan Databases, to
      HCRU and AE rates. METHODS: Total HCRU costs included components for provider
      contacts, diagnostics, hospitalizations, procedures, and study/nonstudy drugs.
      Patients were stratified by the presence or absence of an AE in order to estimate
      costs attributable to AEs. Costs were adjusted to 2013 U.S. dollars. The highest
      1% of cost outliers were equally excluded from each group. Univariate (t-test and
      Kaplan-Meier sample average [KMSA]) and multivariate (using treatment group and
      region as covariates) analyses were performed. RESULTS: A total of 906 patients
      (pazopanib, n = 454; sunitinib, n = 452) reported HCRU; higher rates were
      observed for sunitinib. In unadjusted cost analyses, the mean total costs for
      pazopanib-treated patients were 8.0% lower than those treated with sunitinib
      ($80,464 vs. $86,886; P = 0.20). The difference in KMSA-estimated costs was
      significantly higher for sunitinib versus pazopanib ($156,128 vs. $143,585; P =
      0.003). Adjusted cost differences between arms consistently suggested higher
      costs for sunitinib. Among patients who experienced greater than or equal to 1
      AE, costs were $8,118 higher for pazopanib-treated patients and $14,343 for
      sunitinib-treated patients. CONCLUSIONS: The findings suggest that health care
      costs were lower among patients with advanced RCC treated first-line with
      pazopanib versus sunitinib.

PMID- 25562772
TI  - Cost-effectiveness of pazopanib versus sunitinib for renal cancer in the United
      States.
AB  - BACKGROUND: Current first-line treatments for metastatic renal cell carcinoma
      (mRCC) include the multityrosine kinase inhibitors pazopanib and sunitinib. Both
      agents had similar progression-free survival (PFS) and overall survival (OS) in
      the COMPARZ trial (Comparing the Efficacy, Safety and Tolerability of Pazopanib
      versus Sunitinib); however, the adverse event profiles of the 2 agents are
      different. In the PISCES trial (Patient Preference Study of Pazopanib versus
      Sunitinib in Advanced or Metastatic Kidney Cancer), patients and physicians
      preferred pazopanib primarily because it offered better health-related quality of
      life (HRQoL) and caused less fatigue. OBJECTIVE: To compare the cost
      effectiveness of pazopanib versus sunitinib from a U.S. health care system
      perspective in the first-line treatment of patients with mRCC. METHODS: A
      partitioned-survival analysis model with 3 health states (preprogression,
      postprogression, and dead), data from 2 randomized controlled trials of pazopanib
      versus sunitinib (COMPARZ and PISCES), and secondary sources were used to
      calculate the incremental cost per quality-adjusted life-year (QALY) gained for
      pazopanib versus sunitinib. A time horizon of 37.5 months was used in the base
      case, consistent with the duration of follow-up used in the COMPARZ trial. The
      proportion of patients in each health state over time was based on Kaplan-Meier
      survival distributions for PFS and OS from the COMPARZ trial. Utility values were
      obtained from the PISCES trial. Costs were based on medical resource utilization
      data from the COMPARZ trial and unit costs from secondary sources. Probabilistic
      sensitivity analyses and deterministic sensitivity analyses were conducted.
      RESULTS: In the base case, pazopanib was estimated to provide more QALYs at a
      lower cost compared with sunitinib (pazopanib dominant). In probabilistic
      sensitivity analyses, pazopanib was projected to be dominant in 69% of the
      simulations. The probability that pazopanib was more cost-effective than
      sunitinib was >= 90% for threshold values of cost-effectiveness between the range
      of $10,000-$160,000 per QALY gained. In deterministic sensitivity analyses,
      pazopanib was dominant in all scenarios examined. CONCLUSION: Results of this
      study suggest that pazopanib is cost-effective compared with sunitinib as the
      first-line treatment of patients with mRCC in the United States.

PMID- 25562773
TI  - Cost and consequences of noncompliance to oral bisphosphonate treatment.
AB  - BACKGROUND: Despite the favorable efficacy, safety, and cost-effectiveness
      profile of bisphosphonate (BIS) treatment for osteoporosis (OP), patient
      compliance remains suboptimal. A longer follow-up period could help to better
      characterize patient behavior as well as the predictors of noncompliance because
      of the extended durations of osteoporosis and time to a fracture. OBJECTIVE: To
      determine health care outcomes associated with compliance and noncompliance to
      BIS therapy in women diagnosed with OP. METHODS: This retrospective claims study
      focused on women with OP, who were aged 55 years and older and using oral BIS
      treatment. Patients were identified within the HealthCore Integrated Research
      Environment (HIRE) between January 1, 2007, through June 30, 2010. Patients were
      required to have >= 12 months of pre-index eligibility and >= 24 months of post
      index health plan eligibility. Post-index eligibility was split into 2 periods:
      (1) the compliance time period (the first 12-month post-index period, in which
      compliance was determined) and (2) the cost and consequences time period (13- to
      24-month post-index period during which time health care resource utilization,
      cost, and outcomes were assessed). Noncompliance was defined as medical
      possession ratio (MPR) less than 70%. Descriptive statistics described outcome
      variables for the study population. A logistic regression model determined
      variables predictive of compliance. Further, a generalized linear model was used
      to examine associations between all-cause or OP-related medical/total costs and
      to estimate health care utilization. RESULTS: Of patients overall (N = 27,905),
      59% were noncompliant, and 62% discontinued medication. Among noncompliant
      patients, 6.7% switched BIS therapy (after 64 days average); 97% discontinued (87
      days average); and 21% restarted medication (218 days average). Of noncompliant
      patients, 14% had greater than 1 inpatient visits; 16% had greater than 1
      emergency room visits; 94% had greater than 1 outpatient visits; and 95% had
      greater than 1 office visits. Logistic regression results indicated that under
      aged 65 years (P = 0.012) predicted noncompliance. Relative to the compliant
      group, noncompliant patients had higher fracture rates at post-index second year,
      3.3% vs. 2.4%, and combined second and third years, 6.0% vs. 4.8%, respectively.
      Compared with noncompliant patients, compliant patients had 9% (P = 0.007) lower
      OP-related costs, 3% lower all-cause costs during the second post-index year, and
      11% (P = 0.016) lower OP-related costs. Mean 13- to 24-month post-index period
      all-cause costs were $7,237 for noncompliant patients versus $6,758 for compliant
      patients (P = 0.008). CONCLUSIONS: These results indicate high noncompliance
      rates in this population of older females. OP medication compliance was
      associated with lower fracture rates, OP- and all-cause costs, and health care
      utilization. These findings highlight the financial implications and treatment
      outcomes of BIS medication noncompliance within a female osteoporotic population.

PMID- 25562774
TI  - Economic evaluation of a pharmaceutical care program for elderly diabetic and
      hypertensive patients in primary health care: a 36-month randomized controlled
      clinical trial.
AB  - BACKGROUND: Most diabetic and hypertensive patients, principally the elderly, do
      not achieve adequate disease control and consume 5%-15% of annual health care
      budgets. Previous studies verified that pharmaceutical care is useful for
      achieving adequate disease control in diabetes and hypertension. OBJECTIVE: To
      evaluate the economic cost and the incremental cost-effectiveness ratio (ICER)
      per quality-adjusted life-year (QALY) of pharmaceutical care in the management of
      diabetes and hypertension in elderly patients in a primary public health care
      system in a developing country. METHODS: A 36-month randomized controlled
      clinical trial was performed with 200 patients who were divided into a control
      group (n = 100) and an intervention group (n = 100). The control group received
      the usual care offered by the Primary Health Care Unit (medical and nurse
      consultations). The intervention group received the usual care plus a
      pharmaceutical care intervention. The intervention and control groups were
      compared with regard to the direct costs of health services (i.e., general
      practitioner, specialist, nurse, and pharmacist appointments; emergency room
      visits; and drug therapy costs) and the ICER per QALY. These evaluations used the
      health system perspective. RESULTS: No statistically significant difference was
      found between the intervention and control groups in total direct health care
      costs ($281.97 +/- $49.73 per patient vs. $212.28 +/- $43.49 per patient,
      respectively; P = 0.089); pharmaceutical care added incremental costs of $69.60
      (+/- $7.90) per patient. The ICER per QALY was $53.50 (95% CI = $51.60-$54.00;
      monetary amounts are given in U.S. dollars). Every clinical parameter evaluated
      improved for the pharmaceutical care group, whereas these clinical parameters
      remained unchanged in the usual care group. The difference in differences (DID)
      tests indicated that for each clinical parameter, the patients in the
      intervention group improved more from pre to post than the control group (P <
      0.001). CONCLUSIONS: While pharmaceutical care did not significantly increase
      total direct health care costs, significantly improved health outcomes were seen.
      The mean ICER per QALY gained suggests a favorable cost-effectiveness.

PMID- 25562775
TI  - Tablet splitting: is it worthwhile? Analysis of drug content and weight
      uniformity for half tablets of 16 commonly used medications in the outpatient
      setting.
AB  - BACKGROUND: Tablet splitting is a well-established medical practice in clinical
      settings for multiple reasons, including cost savings and ease of swallowing.
      However, it does not necessarily result in weight-uniform half tablets.
      OBJECTIVES: To (a) investigate the effect of tablet characteristics on weight and
      content uniformity of half tablets, resulting from splitting 16 commonly used
      medications in the outpatient setting and (b) provide recommendations for safe
      tablet-splitting prescribing practices. METHODS: Ten random tablets from each of
      the selected medications were weighed and split by 5 volunteers (2 men and 3
      women aged 25-44 years) using a knife. The selected medications were mirtazapine
      30 mg, bromazepam 3 mg, oxcarbazepin 150 mg, sertraline 50 mg, carvedilol 25 mg,
      bisoprolol fumarate 10 mg, losartan 50 mg, digoxin 0.25 mg, amiodarone HCl 200
      mg, metformin HCl 1,000 mg, glimepiride 4 mg, montelukast 10 mg, ibuprofen 600
      mg, celecoxib 200 mg, meloxicam 15 mg, and sildenafil citrate 50 mg. The
      resulting half tablets were evaluated for weight and drug content uniformity in
      accordance with proxy United States Pharmacopeia (USP) specification (95%-105%
      for digoxin and 90%-110% for the other 15 drugs). Weight and drug content
      uniformity were assessed by comparing weight or drug content of the half tablets
      with one-half of the mean weight or drug content for all whole tablets in the
      sample. The percentages by which the weight and drug content of each whole tablet
      or half tablet differed from sample mean values were calculated. Other relevant
      physical characteristics of the 16 products were measured. RESULTS: A total of 52
      of 320 half tablets (16.2%) and 48 of 320 half tablets (15.0%) fell outside of
      the proxy USP specification for weight and drug content, respectively.
      Bromazepam, carvedilol, bisoprolol, losartan, digoxin, and meloxicam half tablets
      failed the weight and content uniformity test; however, the half tablets for the
      rest of the medications passed the test. Mean percent weight loss after splitting
      was less than 1.5% for all drugs. Bromazepam, carvedilol, and digoxin showed the
      highest powdering loss during the tablet-splitting process. CONCLUSIONS: Tablet
      splitting could be safer and easier when drug- and patient-specific criteria have
      been met. Tablet size, shape, and hardness may also play a role in the decision
      to split a tablet or not. Tablets containing drugs with a wide therapeutic index
      and long half-life might be more suitable candidates for division. Dose variation
      exceeded a proxy USP specification for more than one-third of sampled half
      tablets of bromazepam, carvedilol, bisoprolol, and digoxin. Drug content
      variation in half tablets appeared to be attributed to weight variation due to
      fragment or powder loss during the splitting process.

PMID- 25562776
TI  - Impact of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine use in
      wound management on health care costs and pertussis cases.
AB  - BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends
      the use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis
      (Tdap) vaccine for routine wound management in adolescents and adults who require
      a tetanus toxoid-containing vaccine who were vaccinated >= 5 years earlier with
      tetanus toxoid, reduced diphtheria toxoid (Td) vaccine, and who have not
      previously received Tdap. OBJECTIVE: To estimate the overall budget and health
      impact of vaccinating individuals presenting for wound management with Tdap
      instead of Td vaccine, the current standard of care in practices that do not use
      Tdap for purposes of wound management. METHODS: A decision-analytic economic
      model was developed to estimate the expected increase in direct medical costs and
      the expected number of cases of pertussis avoided associated with the use of Tdap
      instead of Td vaccine in the wound management setting. Patients eligible for Tdap
      were aged 10+ years and required a tetanus-containing vaccine. Age-specific wound
      incidence data and Td and Tdap vaccination rates were taken from the National
      Health Interview Survey and the National Immunization Survey for the most recent
      available year. Age-specific pertussis incidence used in this analysis (151 per
      100,000 for adolescents, 366 per 100,000 for those aged 20-64 years, and 176 per
      100,000 for those aged 65+ years) used reported incidence rates adjusted by a
      factor of 10 for adolescents and by a factor of 100 for adults, based on
      assumptions previously made by ACIP to account for underreporting. Vaccine
      wholesale acquisition costs without federal excise tax were assumed in the base
      case. Efficacy of vaccination with Tdap in preventing pertussis was based on
      clinical trial data. Possible herd immunity effects of vaccination were not
      included in the model. Costs associated with vaccination and treatment of
      pertussis cases were reported as total annual costs and per-member-per-month
      (PMPM) costs for hypothetical health plans and for the U.S. population. Aggregate
      and incremental costs and pertussis cases avoided were presented undiscounted (as
      recommended for budget-impact analyses) annually and cumulatively over a 3-year
      time horizon in 2012 U.S. dollars. Scenario analyses were conducted on key
      parameters, including wound incidence, pertussis incidence, vaccine efficacy and
      waning protection against pertussis, uptake rates for Tdap, and vaccine prices
      using alternative data sources or alternative clinically relevant assumptions.
      RESULTS: For a health plan with 1 million covered lives aged < 65 years,
      vaccination with Tdap instead of Td was estimated to cost an additional $132,364
      ($0.01 PMPM) in the first year and an additional $368,640 ($0.01 PMPM)
      cumulatively over 3 years. For a health plan with 1 million covered lives aged
      65+ years, vaccination with Tdap instead of Td was estimated to cost an
      additional $201,165 ($0.02 PMPM) in the first year and an additional $549,568
      ($0.02 PMPM) cumulatively over 3 years. For the U.S. population aged 10+ years,
      vaccination with Tdap instead of Td was estimated to result in protection against
      pertussis for an additional 2.7 million patients with wounds annually and was
      estimated to cost an additional $121,101,671 to avoid 42,104 cases of pertussis
      over the 3-year time horizon. Results were sensitive to input parameter values,
      particularly parameters associated with the number of patients with wounds
      vaccinated with Tdap (range 2.7 to 5.1 million patients). However, for all of the
      alternative scenarios tested, the expected increase in PMPM costs ranged from <
      $0.01 to $0.03. CONCLUSIONS: Vaccination of adolescents and adults with Tdap for
      wound management may result in an increase in PMPM costs for health plans of <
      $0.01 to $0.03. Given the potential reduction in pertussis cases at the
      population level, vaccination with Tdap for routine wound management could be
      considered as another strategy to help address the pertussis public health
      concern in the United States.

PMID- 25562778
TI  - Composite WO3/TiO2 nanostructures for high electrochromic activity.
AB  - A composite material consisting of TiO2 nanotubes (NT) with WO3 electrodeposited
      on its surface has been fabricated, detached from its Ti substrate, and attached
      to a fluorine-doped tin oxide (FTO) film on glass for application to
      electrochromic (EC) reactions. Several adhesion layers were tested, finding that
      a paste of TiO2 made from commercially available TiO2 nanoparticles creates an
      interface for the TiO2 NT film to attach to the FTO glass, which is conductive
      and does not cause solution-phase ions in an electrolyte to bind irreversibly
      with the material. The effect of NT length and WO3 concentration on the EC
      performance were studied. The composite WO3/TiO2 nanostructures showed higher ion
      storage capacity, better stability, enhanced EC contrast, and longer memory time
      compared with the pure WO3 and TiO2 materials. 

PMID- 25562777
TI  - The US Food and Drug Administration's perspective on the new antidepressant
      vortioxetine.
AB  - OBJECTIVE: This article summarizes the US Food and Drug Administration's (FDA's)
      review of the New Drug Application for vortioxetine, especially the clinical
      efficacy and safety data. It emphasizes the issues that were important to the
      FDA's approval decision, particularly the difference in the effective dose in
      domestic and foreign studies, and notes several new labeling features,
      specifically, description of time course of treatment response and detailed
      sexual dysfunction evaluation. DATA SOURCES: The data sources were the original
      raw data sets for all clinical trials included in the development program for
      vortioxetine, as well as the sponsor's original analyses of these data. Data were
      available from 51 human trials involving vortioxetine, and included a total of
      7,666 healthy volunteers and patients with a diagnosis of major depressive
      disorder (MDD) or generalized anxiety disorder who were exposed to at least 1
      dose of vortioxetine for a total of 2,743 patient-years. RESULTS: Vortioxetine
      was effective in treating MDD in the United States at a dose of 20 mg/d. The
      recommended starting dose is 10 mg once daily without regard to food, with
      increase to 20 mg/d if the 10 mg/d dose is tolerated. For patients who do not
      tolerate 20 mg/d, 10 mg/d can be used and 5-mg/d dose can be considered.
      Vortioxetine can be discontinued abruptly, but it is recommended that doses of 15
      mg/d or 20 mg/d be reduced to 10 mg/d for 1 week prior to full discontinuation to
      avoid potential withdrawal symptoms. Although the non-US maintenance study showed
      that maintenance doses of 5 to 10 mg/d were effective, a clinical judgment needs
      to be made to decide the maintenance dose in the United States. The applicant has
      agreed to conduct a US maintenance dose-response study covering the US-approved
      dose range. Vortioxetine's adverse event profile is similar to that of other
      selective serotonin reuptake inhibitors (SSRIs). Nausea is the most common
      adverse event and is dose dependent. No dose adjustment is needed based on age,
      gender, or the presence of renal or mild to moderate hepatic impairment. The
      maximum recommended dose is 10 mg/d in known cytochrome P450 2D6 poor
      metabolizers. CONCLUSIONS: Vortioxetine is a new treatment for MDD, and its
      adverse event profile is similar to that of other SSRIs.

PMID- 25562779
TI  - The CRE1 cytokinin pathway is differentially recruited depending on Medicago
      truncatula root environments and negatively regulates resistance to a pathogen.
AB  - Cytokinins are phytohormones that regulate many developmental and environmental
      responses. The Medicago truncatula cytokinin receptor MtCRE1 (Cytokinin Response
      1) is required for the nitrogen-fixing symbiosis with rhizobia. As several
      cytokinin signaling genes are modulated in roots depending on different biotic
      and abiotic conditions, we assessed potential involvement of this pathway in
      various root environmental responses. Phenotyping of cre1 mutant roots infected
      by the Gigaspora margarita arbuscular mycorrhizal (AM) symbiotic fungus, the
      Aphanomyces euteiches root oomycete, or subjected to an abiotic stress (salt),
      were carried out. Detailed histological analysis and quantification of cre1
      mycorrhized roots did not reveal any detrimental phenotype, suggesting that
      MtCRE1 does not belong to the ancestral common symbiotic pathway shared by
      rhizobial and AM symbioses. cre1 mutants formed an increased number of emerged
      lateral roots compared to wild-type plants, a phenotype which was also observed
      under non-stressed conditions. In response to A. euteiches, cre1 mutants showed
      reduced disease symptoms and an increased plant survival rate, correlated to an
      enhanced formation of lateral roots, a feature previously linked to Aphanomyces
      resistance. Overall, we showed that the cytokinin CRE1 pathway is not only
      required for symbiotic nodule organogenesis but also affects both root
      development and resistance to abiotic and biotic environmental stresses. 

PMID- 25562781
TI  - Active matrix metalloproteases are expressed early on and are high during the
      Barrett's esophagus malignancy sequence.
AB  - OBJECTIVE: Molecular processes underlying Barrett's malignant development are
      poorly understood. Matrix metalloproteases (MMPs) are enzymes involved in
      inflammation, tissue remodeling, and malignant development. Therefore, active
      MMPs may have a role in early metaplasia development and Barrett's esophagus'
      malignant progression. We desired to gain more insight into the role of MMPs
      during the Barrett's esophagus pathogenesis sequence. MATERIAL AND METHODS: In a
      surgical Barrett's mouse model, and in nonmalignant Barrett's and malignant
      esophageal cell lines, the activity of MMPs was investigated using a MMP
      activatable probe. MMP activity was further validated in Barrett's esophagus and
      esophageal adenocarcinoma patient biopsies and was further differentiated by
      investigating MMP9 and MMP13 expressions. RESULTS: The mouse model showed probe
      activation in stromal cells early on in the esophagitis and metaplasia stages.
      MMP probe activation was higher in the Barrett's and cancer cell lines and
      biopsies as compared to normal cells and tissues. Co-immunostainings confirmed
      that, at the tissue level, the probe activation was mostly confined to CD45
      positive stromal cells. MMP13 expression was highest in Barrett's metaplasia,
      whereas MMP9 was highest in the esophageal adenocarcinomas. CONCLUSION: During
      the Barrett's pathogenesis process, MMP activity is increased early on in the
      inflamed esophagus and remains high in metaplasia and esophageal adenocarcinoma.
      However, there is a switch of MMP13 to MMP9 expression once neoplasia develops.
      In the future, detecting specific MMP subtypes could be used for distinguishing
      nonmalignant from neoplastic Barrett's esophagus.

PMID- 25562783
TI  - Silicon nanoparticles obtained via a low temperature chemical "metathesis"
      synthesis route and their lithium-ion battery properties.
AB  - Silicon (Si) nanoparticles have been prepared by a "metathesis" reaction of
      magnesium silicide (Mg2Si) and zinc chloride (ZnCl2) in an autoclave at 300 
      degrees C. The as-prepared Si nanoparticles exhibit a reversible capacity of 795
      mA h g(-1) at a current density of 3.6 A g(-1) over 250 cycles. 

PMID- 25562780
TI  - Kinetic gating mechanism of DNA damage recognition by Rad4/XPC.
AB  - The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by
      recognizing DNA lesions before recruiting downstream factors. How XPC detects
      structurally diverse lesions embedded within normal DNA is unknown. Here we
      present a crystal structure that captures the yeast XPC orthologue (Rad4) on a
      single register of undamaged DNA. The structure shows that a disulphide-tethered
      Rad4 flips out normal nucleotides and adopts a conformation similar to that seen
      with damaged DNA. Contrary to many DNA repair enzymes that can directly reject
      non-target sites as structural misfits, our results suggest that Rad4/XPC uses a
      kinetic gating mechanism whereby lesion selectivity arises from the kinetic
      competition between DNA opening and the residence time of Rad4/XPC per site. This
      mechanism is further supported by measurements of Rad4-induced lesion-opening
      times using temperature-jump perturbation spectroscopy. Kinetic gating may be a
      general mechanism used by site-specific DNA-binding proteins to minimize time
      consuming interrogations of non-target sites. 

PMID- 25562782
TI  - Pain: a distributed brain information network?
AB  - Understanding how pain is processed in the brain has been an enduring puzzle,
      because there doesn't appear to be a single "pain cortex" that directly codes the
      subjective perception of pain. An emerging concept is that, instead, pain might
      emerge from the coordinated activity of an integrated brain network. In support
      of this view, Woo and colleagues present evidence that distinct brain networks
      support the subjective changes in pain that result from nociceptive input and
      self-directed cognitive modulation. This evidence for the sensitivity of distinct
      neural subsystems to different aspects of pain opens up the way to more formal
      computational network theories of pain. 

PMID- 25562784
TI  - Na insertion mechanisms in vanadium oxide nanotubes for Na-ion batteries.
AB  - In this study, we successfully synthesized lamellar-structured Ni0.1VOx NTs by a
      microwave-assisted hydrothermal method and cation exchange reaction. High initial
      discharge capacity and 100% efficiency were obtained when the Ni0.1VOx NTs
      cathode was used as a cathode material for the Na battery. The intercalation
      mechanism and capacity fading effect were investigated in detail both
      experimentally using Transmission electron microscopy (TEM), X-ray diffraction
      (XRD), Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron
      spectroscopy (XPS) analyses and theoretically using the ab initio simulation
      method. During the intercalation of Na(+) into VOx NT structures, TEM, XRD, FT
      IR, and XPS data revealed the cointercalation of the solvent, resulting in the
      expansion of the interlayer spacing and carbon and oxygen adsorption. The
      experimental and simulation results suggest that solvent molecules coordinated
      the Na insertion mechanisms into the amine interlayer during discharging. These
      understandings of the Na intercalation mechanism in materials based on Ni0.1VOx
      NTs would be useful to design more stable and high-performance VOx-based
      electrodes for Na battery applications. 

PMID- 25562785
TI  - Structural determinants in a library of low molecular weight gelators.
AB  - Low molecular weight hydrogels are formed by molecules that form a matrix that
      immobilises water to form a self-supporting gel. Such gels have uses as
      biomaterials such as molecular scaffolds and structures for tissue engineering.
      One class of low molecular weight gelator (LMWG), naphthalene-conjugated
      dipeptides, has been shown to form hydrogels via self-assembly following a
      controlled drop in pH. A library of naphthalene-dipeptides has been generated
      previously although the relationship between the precursor sequence and the
      resulting self-assembled structures remained unclear. Here, we have investigated
      the structural details of a set of dipeptide sequences containing alanine (A) and
      valine (V) conjugated to naphthalene groups substituted with a Br, CN or H at the
      6-position. Electron microscopy, circular dichroism and X-ray fibre diffraction
      shows that these LMWG may be structurally classified by their composition: the
      molecular packing is determined by the class of conjugate, whilst the chirality
      of the self-assemblies can be attributed to the dipeptide sequence. This provides
      insights into the relationship between the precursor sequence and the
      macromolecular and molecular structures of the fibres that make up the resulting
      hydrogels. 

PMID- 25562787
TI  - Widow discrimination and family caregiving in India: evidence from microdata
      collected from six major cities.
AB  - The purpose of this research is to address the lack of a region-wide view of
      widow discrimination in India, the home of 42 million widows. This study analyzed
      the household data collected in face-to-face interviews from January to March of
      2011 in six major Indian cities. It was revealed that widow discrimination does
      not prevail across the nation. That is, this research did not deny the existence
      of traditional widow discrimination in some areas but demonstrated that this
      phenomenon does not represent the whole nation if we focus on the widows' old age
      and the treatment by their families. 

PMID- 25562786
TI  - A ferromagnetically coupled Fe42 cyanide-bridged nanocage.
AB  - Self-assembly of artificial nanoscale units into superstructures is a prevalent
      topic in science. In biomimicry, scientists attempt to develop artificial self
      assembled nanoarchitectures. However, despite extensive efforts, the preparation
      of nanoarchitectures with superior physical properties remains a challenge. For
      example, one of the major topics in the field of molecular magnetism is the
      development of high-spin (HS) molecules. Here, we report a cyanide-bridged
      magnetic nanocage composed of 18 HS iron(III) ions and 24 low-spin iron(II) ions.
      The magnetic iron(III) centres are ferromagnetically coupled, yielding the
      highest ground-state spin number (S = 45) of any molecule reported to date.

PMID- 25562788
TI  - Evaluation of dual nasal delivery of infectious hematopoietic necrosis virus and
      enteric red mouth vaccines in rainbow trout (Oncorhynchus mykiss).
AB  - Farmed fish are susceptible to different infectious disease agents including
      viruses and bacteria. Thus, multivalent vaccines or vaccination programs against
      two or more pathogens are valuable tools in aquaculture. Recently, nasal vaccines
      have been shown to be very effective in rainbow trout. The current study
      investigates, for the first time, the use of the nasal route in dual vaccination
      trials against two important aquatic diseases, infectious hematopoietic necrosis
      virus (IHN) and enteric red mouth (ERM) disease. Rainbow trout received live
      attenuated IHN virus (IHNV) vaccine and the ERM bacterin using four different
      vaccine delivery methods and were challenged with virulent IHNV or Yersinia
      ruckeri 7 (100 deg day) and 28 (400 deg day) days post-vaccination. The highest
      survival rates against IHNV at day 7 were obtained by nasal vaccination either
      when IHNV and ERM were delivered separately into each nare or when they were
      premixed and delivered to both nasal rosettes (group D). Protection at 28 days
      against IHNV was similar in all four vaccinated groups. Early protection against
      ERM was highest in fish that received each vaccine in separate nares (group B),
      whereas protection at 28 days was highest in the i.p. vaccinated group (group E),
      followed by the nasally vaccinated group (group B). Survival results were
      supported by histological observations of the left and right olfactory organ
      which showed strong immune responses one day (14 deg days) after vaccination in
      group B vaccinated fish. These data indicate that dual vaccination against two
      different pathogens via the nasal route is a very effective vaccination strategy
      for use in aquaculture, particularly when each nare is used separately during
      delivery. Further long-term studies should evaluate the contribution of adaptive
      immunity to the protection levels observed.

PMID- 25562789
TI  - A recombinant field strain of Marek's disease (MD) virus with
      reticuloendotheliosis virus long terminal repeat insert lacking the meq gene as a
      vaccine against MD.
AB  - Marek's disease virus (MDV) GX0101, which is a field strain with a naturally
      occurring insertion of the reticuloendotheliosis virus (REV) long terminal repeat
      (LTR) fragment, shows distinct biological activities. Deletion of the meq gene in
      GX0101 contributes to its complete loss of pathogenicity and oncogenicity in SPF
      chickens, but this virus has a kanamycin resistance gene (kan(r)) residual at the
      site of meq gene. In the present study, the kan(r) was knocked out and a meq-null
      virus with a good replicative ability termed SC9-1 was selected. In vivo studies
      showed that SC9-1 had no pathogenicity or tumorigenicity to chickens. There were
      no obvious impacts on chicken weight, immune organ index or antibody levels
      induced by avian influenza virus (AIV)/newcastle disease virus (NDV) inactivated
      vaccines compared with the control group. The SC9-1 virus provided superior
      protection than CVI988/Rispens vaccine in both SPF chickens and Hy-line brown
      chickens when challenged with a very virulent MDV (rMd5 strain). There was no
      obvious change in SC9-1 protection against MDV rMd5 in SPF chickens after 20
      passages in chicken embryonic fibroblast cells (CEFs). In conclusion, SC9-1 is a
      safe and effective vaccine candidate for the prevention of Marek's disease. 

PMID- 25562790
TI  - Early exposure to the combined measles-mumps-rubella vaccine and thimerosal
      containing vaccines and risk of autism spectrum disorder.
AB  - OBJECTIVE: This case-control study investigated the relationship between the risk
      of Autism Spectrum Disorder (ASD) onset, and early exposure to the combined
      Measles-Mumps-Rubella (MMR) vaccine and thimerosal consumption measured from
      vaccinations in the highly genetically homogenous Japanese population. METHODS:
      Vaccination histories at 1, 3, 6, 12, 18, 24, and 36 months from birth were
      investigated in ASD cases (189 samples), and controls (224 samples) matching age
      and sex in each case. Crude odds ratios (ORs) and 95% confidence intervals (95%
      CIs) were calculated to determine relationship between MMR vaccination and ASD.
      The differences in mean values of the thimerosal dosage between cases and
      controls were analyzed using an unpaired t-test. MMR vaccination and thimerosal
      dosage were also investigated using a conditional multiple-regression model.
      RESULTS: There were no significant differences in MMR vaccination and thimerosal
      dosage between cases and controls at any age. Furthermore, the ORs (95% CIs) of
      MMR vaccination and thimerosal dosage associated with ASD in the conditional
      multiple regression model were, respectively, 0.875 (0.345-2.222) and 1.205
      (0.862-1.683) at age 18 months, 0.724 (0.421-1.243) and 1.343 (0.997-1.808) at 24
      months, and 1.040 (0.648-1.668) and 0.844 (0.632-1.128) at 36 months. Thus, there
      were no significant differences. CONCLUSIONS: No convincing evidence was found in
      this study that MMR vaccination and increasing thimerosal dose were associated
      with an increased risk of ASD onset.

PMID- 25562792
TI  - KISS1 can be used as a novel target for developing a DNA immunocastration vaccine
      in ram lambs.
AB  - KISS1 gene-encoding kisspeptins are critical for the onset of puberty and control
      of adult fertility. This study investigated whether KISS1 can be used as a novel
      target for immunocastration. Human KISS1 was fused with the HBsAg-S gene for
      constructing an antibiotic-free recombinant plasmid pKS-asd that coded for 31.168
      kDa target fusion protein. Six male Hu sheep lambs were divided into two equal
      groups, treatment and control. The vaccine (1mg/ram lamb) prepared in saline
      solution was injected into lambs at weeks 0, 3 and 6 of the experiment,
      respectively. Vaccine efficacy was evaluated in terms of KISS1-specific IgG
      antibody response, serum testosterone levels, scrotal circumference, testicular
      weight, length and breadth, extent of testicular tissue damage, and sexual
      behaviour changes. The specific anti-KISS1 antibody titre in vaccinated animals
      was significantly higher than that in controls (p<0.05). In addition, vaccinated
      animals showed lower serum testosterone level, testicular weight and length and
      smaller scrotal circumference than those in controls (p<0.05). Spermatogenesis of
      seminiferous tubules in vaccinated animals was suppressed; sexual behaviours in
      vaccinated animals were significantly lower (p<0.05) than those in controls. In
      conclusion, the immunization against KISS1 in this DNA vaccine induced a strong
      antibody response and resulted in the suppression of gonadal function and sexual
      behaviour in animals, demonstrating that KISS1 can be used as a novel target for
      developing a DNA immunocastration vaccine.

PMID- 25562793
TI  - Comparison of subcutaneous versus intranasal immunization of male koalas
      (Phascolarctos cinereus) for induction of mucosal and systemic immunity against
      Chlamydia pecorum.
AB  - Chlamydia pecorum infections are debilitating in the koala, contributing
      significantly to morbidity and mortality, with current antibiotic treatments
      having minimal success and adversely affecting gut microflora. This, combined
      with the sometimes-asymptomatic nature of the infection, suggests that an
      efficacious anti-chlamydial vaccine is required to control chlamydial infections
      in the koala. To date vaccination studies have focused primarily on female
      koalas, however, given the physiological differences between male and female
      reproductive tracts, we tested the efficacy of a vaccine in 12 captive male
      koalas. We evaluated the potential of both subcutaneous and intranasal vaccine
      delivery to elicit mucosal immunity in male koalas. Our results showed that both
      intranasal and subcutaneous delivery of a vaccine consisting of C. pecorum major
      outer membrane protein (MOMP) and the adjuvant immunostimulating complex (ISC)
      induced significant immune responses in male koalas. Subcutaneous immunization
      elicited stronger cell-mediated responses in peripheral blood lymphocytes (PBL),
      and greater plasma antibody levels whereas the intranasal immunization elicited
      stronger humoral responses in urogenital tract (UGT) secretions. This is the
      first time a Chlamydia vaccine has been tested in the male koala and the first
      assessment of a mucosal vaccination route in this species. Our results suggest
      that vaccination of male koalas can elicit mucosal immunity and could contribute
      to the long-term survivability of wild populations of the koala. 

PMID- 25562791
TI  - A West Nile virus NS4B-P38G mutant strain induces cell intrinsic innate cytokine
      responses in human monocytic and macrophage cells.
AB  - Previous studies have shown that an attenuated West Nile virus (WNV)
      nonstructural (NS) 4B-P38G mutant induces stronger innate and adaptive immune
      responses than wild-type WNV in mice, which has important applications to vaccine
      development. To investigate the mechanism of immunogenicity, we characterized WNV
      NS4B-P38G mutant infection in two human cell lines-THP-1 cells and THP-1
      macrophages. Although the NS4B-P38G mutant produced more viral RNA than the
      parental WNV NY99 in both cell types, there was no detectable infectious virus in
      the supernatant of either cell type. Nonetheless, the attenuated mutant boosted
      higher innate cytokine responses than virulent parental WNV NY99 in these cells.
      The NS4B-P38G mutant infection of THP-1 cells led to more diverse and robust
      innate cytokine responses than that seen in THP-1 macrophages, which were
      mediated by toll-like receptor (TLR)7 and retinoic acid-inducible gene 1(RIG-I)
      signaling pathways. Overall, these results suggest that a defective viral life
      cycle during NS4B-P38G mutant infection in human monocytic and macrophage cells
      leads to more potent cell intrinsic innate cytokine responses. 

PMID- 25562794
TI  - Gas chromatographic determination of ethyl glucuronide in hair: comparison
      between tandem mass spectrometry and single quadrupole mass spectrometry.
AB  - Ethyl glucuronide (EtG), a minor metabolite of ethanol, accumulates in hair and
      is currently used as a long-term marker for the detection of chronic and
      excessive alcohol consumption. Sensitive methods are required to differentiate
      teetotalers from moderate drinkers according to the established cut-off (i.e., 7
      pg/mg hair). The aim of this study was to develop a sensitive method using gas
      chromatography coupled to tandem mass spectrometry (GC-MS/MS) operated in the
      negative ion chemical ionization (NICI) mode. The validated method was applied to
      hair samples from teetotalers, moderate and excessive alcohol consumers, and
      results were compared to a previously validated GC-NICI-MS method. The developed
      GC-NICI-MS/MS method showed linearity over a range from 2 to 400 pg/mg hair, with
      a limit of detection (LOD) of 0.05 pg/mg hair and a lower limit of quantification
      (LLOQ) of 0.2 pg/mg hair, compared to an LOD of 0.5 pg/mg hair and LLOQ of 1.5
      pg/mg hair obtained with GC-NICI-MS. Furthermore, lower background noise was
      observed using GC-NICI-MS/MS. Comparison of results of hair samples (n=58)
      obtained by GC-NICI-MS and GC-NICI-MS/MS showed no significant difference between
      both methods (paired-sample t-test, p>0.05; mean CV=1.0%). The differences
      between both methods were larger for EtG concentrations<30 mg/pg hair (mean
      CV=1.7%) than for EtG concentrations>30 mg/pg hair (mean CV=0.7%). This suggests
      a higher selectivity of GC-NICI-MS/MS at lower concentrations. In conclusion, by
      using GC-NICI-MS/MS, a higher analytical selectivity and an improved signal to
      noise ratio, can be achieved. Although GC-NICI-MS would not change the
      interpretation of the EtG concentrations, the present GC-NICI-MS/MS method should
      preferentially be used for the determination of EtG in hair, especially when
      differentiating between teetotalers and moderate drinkers according to the
      current cut-off (i.e., 7 pg/mg hair).

PMID- 25562795
TI  - Ripplocations in van der Waals layers.
AB  - Dislocations are topological line defects in three-dimensional crystals. Same
      sign dislocations repel according to Frank's rule |b1 + b2|(2) > |b1|(2) +
      |b2|(2). This rule is broken for dislocations in van der Waals (vdW) layers,
      which possess crystallographic Burgers vector as ordinary dislocations but
      feature "surface ripples" due to the ease of bending and weak vdW adhesion of the
      atomic layers. We term these line defects "ripplocations" in accordance to their
      dual "surface ripple" and "crystallographic dislocation" characters. Unlike
      conventional ripples on noncrystalline (vacuum, amorphous, or fluid) substrates,
      ripplocations tend to be very straight, narrow, and crystallographically
      oriented. The self-energy of surface ripplocations scales sublinearly with |b|,
      indicating that same-sign ripplocations attract and tend to merge, opposite to
      conventional dislocations. Using in situ transmission electron microscopy, we
      directly observed ripplocation generation and motion when few-layer MoS2 films
      were lithiated or mechanically processed. Being a new subclass of elementary
      defects, ripplocations are expected to be important in the processing and defect
      engineering of vdW layers. 

PMID- 25562796
TI  - Concentrations of 6-thioguanine nucleotide correlate with trough levels of
      infliximab in patients with inflammatory bowel disease on combination therapy.
AB  - BACKGROUND & AIMS: In patients with inflammatory bowel diseases, the combination
      of infliximab and thiopurines (such as 6-thioguanine) is more effective treatment
      than monotherapy. We assessed the correlation between serum levels of 6
      thioguanine (6-TGN) and infliximab levels or antibodies to infliximab (ATI).
      METHODS: We performed a cross-sectional study of 72 patients receiving
      maintenance therapy with infliximab and a thiopurine for inflammatory bowel
      disease at the Crohn's and Colitis Center of the University of Miami, FL. We
      collected clinical, endoscopic, and biochemical data, and levels of thiopurine
      metabolites. The primary outcomes were trough level of infliximab and the
      presence of ATI. RESULTS: Levels of 6-TGN correlated with those of infliximab
      (rho, 0.53; P < .0001). The cut-off point of 6-TGN that best predicted a higher
      level of infliximab was 125 pmol/8 * 10(8) red blood cells (RBCs) (area under
      receiver operating characteristic, 0.86; P < .001). Patients in the lowest
      quartile of 6-TGN had infliximab levels that were similar to patients on no
      thiopurines (4.3 vs. 4.8 mcg/mL, respectively; P = .8). An infliximab level of
      8.3 mcg/mL or greater was associated with mucosal healing. Only 8 patients (11%)
      had detectable ATI. Patients with 6-TGN levels less than 125 pmol/8 * 10(8) RBCs
      were significantly more likely to have ATI (odds ratio, 1.3; 95% confidence
      interval, 2.3-72.5; P < .01). CONCLUSIONS: Although 6-TGN levels of greater than
      230 pmol/8 * 10(8) RBCs have been associated with improved outcomes in patients
      on monotherapy, a level of 6-thioguanine of 125 pmol/8 * 10(8) RBCs or greater
      may be adequate to achieve therapeutic levels of infliximab. In the long term,
      this may minimize the toxicity for patients on combination therapy.

PMID- 25562797
TI  - Immunohistochemical analysis of eosinophilic esophagitis.

PMID- 25562798
TI  - Molecular therapeutic advances in personalized therapy of melanoma and non-small
      cell lung cancer.
AB  - The incorporation of individualized molecular therapeutics into routine clinical
      practice for both non-small cell lung cancer (NSCLC) and melanoma are amongst the
      most significant advances of the last decades in medical oncology. In NSCLC
      activating somatic mutations in exons encoding the tyrosine kinase domain of the
      Epidermal Growth Factor Receptor (EGFR) gene have been found to be predictive of
      a response to treatment with tyrosine kinase inhibitors (TKI), erlotinib or
      gefitinib. More recently the EML4-ALK fusion gene which occurs in 3-5% of NSCLC
      has been found to predict sensitivity to crizotinib an inhibitor of the
      anaplastic lymphoma kinase (ALK) receptor tyrosine kinase. Similarly in melanoma,
      50% of cases have BRAF mutations in exon 15 mostly V600E and these cases are
      sensitive to the BRAF inhibitors vemurafenib or dabrafenib. In a Phase III study
      of advanced melanoma cases with this mutation vemurafenib improved survival from
      64% to 84% at 6 months, when compared with dacarbazine. In both NSCLC and
      melanoma clinical benefit is not obtained in patients without these genomic
      changes, and moreover in the case of vemurafenib the therapy may theoretically
      induce proliferation of cases of melanoma without BRAF mutations. An emerging
      clinical challenge is that of acquired resistance after initial responses to
      targeted therapeutics. Resistance to the TKI's in NSCLC is most frequently due to
      acquisition of secondary mutations within the tyrosine kinase of the EGFR or
      alternatively activation of alternative tyrosine kinases such as C-MET.
      Mechanisms of drug resistance in melanoma to vemurafenib do not involve mutations
      in BRAF itself but are associated with a variety of molecular changes including
      RAF1 or COT gene over expression, activating mutations in RAS or increased
      activation of the receptor tyrosine kinase PDGFRbeta. Importantly these data
      support introducing re-biopsy of tumors at progression to continue to personalize
      the choice of therapy throughout the patient's disease course. 

PMID- 25562800
TI  - Phospholamban pentamers attenuate PKA-dependent phosphorylation of monomers.
AB  - Phospholamban (PLN) is a key regulator of cardiac contraction and relaxation
      through its inhibition of the sarco/endoplasmic reticulum Ca(2+)-ATPase
      (SERCA2a). The inhibitory effect is attenuated upon protein kinase A (PKA)
      dependent phosphorylation of PLN. PLN exists in an equilibrium of pentamers and
      monomers. While monomers inhibit SERCA2a by direct interaction, the function of
      the pentamers is still unclear. Here, we tested the hypothesis that the PLN
      pentamer exhibits an important regulatory role by modifying PKA-dependent
      phosphorylation of inhibitory monomeric PLN subunits. Using Western blot analyses
      and antibodies specific for PKA-dependent phosphorylation of PLN, pentamers
      showed stronger signals than monomers both in transfected HEK293 cells and in
      cardiomyocytes. Upon activation of PKA, phosphorylation of protomers in the PLN
      pentamers increased faster and at lower levels of stimulation than PLN monomers,
      suggesting pentamers as the preferred PKA target. The comparison of
      phosphorylation patterns at different pentamer/monomer ratios revealed that
      pentamers delay phosphorylation of PLN monomers. A mechanistic explanation was
      provided by co-immunoprecipitation that suggested high affinity of PKA for PLN
      pentamers. Both monomers and pentamers were pulled down with SERCA2a indicating
      co-localization. Unlike pentamers, phosphorylated PLN monomers fully dissociated
      from the Ca(2+)-ATPase upon stimulation of PKA. These findings suggest a model
      where PLN pentamers reduce phosphorylation of monomers at baseline and delay
      monomer phosphorylation upon PKA stimulation leading to increased interaction of
      PLN monomers with SERCA2a. 

PMID- 25562799
TI  - Infectious Disease Management through Point-of-Care Personalized Medicine
      Molecular Diagnostic Technologies.
AB  - Infectious disease management essentially consists in identifying the microbial
      cause(s) of an infection, initiating if necessary antimicrobial therapy against
      microbes, and controlling host reactions to infection. In clinical microbiology,
      the turnaround time of the diagnostic cycle (>24 hours) often leads to
      unnecessary suffering and deaths; approaches to relieve this burden include rapid
      diagnostic procedures and more efficient transmission or interpretation of
      molecular microbiology results. Although rapid nucleic acid-based diagnostic
      testing has demonstrated that it can impact on the transmission of hospital
      acquired infections, we believe that such life-saving procedures should be
      performed closer to the patient, in dedicated 24/7 laboratories of healthcare
      institutions, or ideally at point of care. While personalized medicine generally
      aims at interrogating the genomic information of a patient, drug metabolism
      polymorphisms, for example, to guide drug choice and dosage, personalized
      medicine concepts are applicable in infectious diseases for the (rapid)
      identification of a disease-causing microbe and determination of its
      antimicrobial resistance profile, to guide an appropriate antimicrobial treatment
      for the proper management of the patient. The implementation of point-of-care
      testing for infectious diseases will require acceptance by medical authorities,
      new technological and communication platforms, as well as reimbursement practices
      such that time- and life-saving procedures become available to the largest number
      of patients. 

PMID- 25562801
TI  - Ectopic automaticity induced in ventricular myocytes by transgenic overexpression
      of HCN2.
AB  - Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) are expressed
      in the ventricles of fetal hearts but are normally down-regulated as development
      progresses. In the hypertrophied heart, however, these channels are re-expressed
      and generate a hyperpolarization-activated, nonselective cation current (Ih),
      which evidence suggests may increase susceptibility to arrhythmia. To test this
      hypothesis, we generated and analyzed transgenic mice overexpressing HCN2
      specifically in their hearts (HCN2-Tg). Under physiological conditions, HCN2-Tg
      mice exhibited no discernible abnormalities. After the application of
      isoproterenol (ISO), however, ECG recordings from HCN2-Tg mice showed
      intermittent atrioventricular dissociation followed by idioventricular rhythm.
      Consistent with this observation, 0.3 MUmol/L ISO-induced spontaneous action
      potentials (SAPs) in 76% of HCN2-Tg ventricular myocytes. In the remaining 24%,
      ISO significantly depolarized the resting membrane potential (RMP), and the late
      repolarization phase of evoked action potentials (APs) was significantly longer
      than in WT myocytes. Analysis of membrane currents revealed that these
      differences are attributable to the Ih tail current. These findings suggest HCN2
      channel activity reduces the repolarization reserve of the ventricular action
      potential and increases ectopic automaticity under pathological conditions such
      as excessive beta-adrenergic stimulation.

PMID- 25562802
TI  - Silver-mediated radical cyclization of alkynoates and alpha-keto acids leading to
      coumarins via cascade double C-C bond formation.
AB  - A novel and convenient silver-mediated radical cyclization method for the
      synthesis of coumarin derivatives via the direct difunctionalization of
      alkynoates with alpha-keto acids through double C-C bond formation under mild
      conditions has been developed. This new method is highly efficient and practical,
      and the starting materials are readily prepared. The present method should
      provide a useful strategy for the construction of coumarin motifs. 

PMID- 25562803
TI  - Synthesis, characterization and magnetism of metal-organic compounds: role of the
      positions of the coordinating groups of a meso-flexible ligand in placing
      anisotropy to exhibit spin-canting behaviour.
AB  - In continuation of our recent investigation on flexible ligands, three new metal
      organic coordination framework containing compounds, formulated as
      {Co(2)(L2)2(px3ampy)(2)}(n).npx3ampy (1), {Co(L2)(px3ampy)(0.5)}(n) (2) and
      {Co(2)(L3) (px3ampy)(2)(H(2)O)}(n).3nH(2)O (3) have been synthesized using three
      structurally different meso-flexible polycarboxylate ligands, H(2)L1(4,4'
      methylenebis-(oxy)dibenzoic acid), H(2)L2 (3,3'-methylenebis-(oxy)dibenzoic acid)
      and H(4)L3 (5,5'-methylene-bis(oxy)diisophthalic acid) bearing the flexible
      spacer in the middle of the skeleton, along with a long flexible pyridyl ligand
      px3ampy (1,4-bis(3-pyridylaminomethyl)benzene). Compounds 1-3 have been
      characterized by single crystal X-ray diffraction analysis, IR spectroscopy and
      thermogravimetric (TG) studies including elemental analysis. The crystal
      structure determinations reveal that compound 1 has a 1D ladder-like structure
      and compounds 2and 3 are characterized by 3D frameworks. Compound 2 possesses a
      tiling of a snz net and compound 3 has a 3D interpenetrated motif with a (4,4)
      connecting 2-nodal net. The variable temperature magnetic susceptibility
      measurements demonstrate the dominating antiferromagnetic nature of all three
      title compounds; interestingly, however, compounds 2 and 3 exhibit ferromagnetic
      interactions due to the uncompensated magnetic moment of the system at low
      temperatures. Compound 2 illustrates the occurrence of spin canted
      antiferromagnetic ordering at T(c) ~ 25 K with a coercive field (H(c)) of 900 Oe
      at 10 K due to the inclusion of magnetic anisotropy caused by the twisting of the
      concerned ligand skeleton. Compound shows comparatively weak ferromagnetic
      ordering with T(c) ~ 9.5 K, for which weak magnetic anisotropy is present because
      of two different coordination environments (octahedral and tetrahedral) between
      two cobalt centers. A structure-function relationship has been described based on
      the position of the coordinating groups with respect to the flexible center of
      the ligand skeleton as well as the coordination angle between the ligand and the
      metal ion.

PMID- 25562804
TI  - New flavonoid glycosides from Sedum aizoon L.
AB  - Five new flavonoid glucosides (3-4, 10-12) and a new phenolic derivative (5),
      together with eight known compounds including three flavonoid glucosides (6-8),
      three phenolic compounds (1-2, 9) and two megastigmane glucosides (13, 14), were
      isolated from the ethanol extract of the aerial part of Sedum aizoon L. Among
      them, compounds 9, 13 and 14 were isolated and identified from this genus for the
      first time. The structures of compounds were elucidated on the basis of 1D and 2D
      NMR (HSQC, HMBC and COSY) spectra and the HR-ESI-MS data. These compounds were
      tested for their antibacterial efficacies against both Gram-positive and Gram
      negative bacteria. Compounds 1, 2, 3, 7 and 10 showed certain antibacterial
      activity; it showed more potency against Gram-positive than against Gram-negative
      bacteria. Compound 2 showed the most pronounced antibacterial effectiveness
      against Staphylococcus aureus Rosenbach with MIC value of 7.8MUg.mL(-1). The in
      vitro anti-proliferative activities against HepG2, MCF-7 and A549 tumor cell
      lines were also evaluated. The result suggested compound 7 exhibited moderate
      cytotoxic activities with IC50 values of 46.30, 75.27 and 49.76MUmol/L,
      respectively. 

PMID- 25562805
TI  - Anti-complement sesquiterpenes from Viola yedoensis.
AB  - Two new germacrane sesquiterpenes, yedoensins A (1) and B (2), together with 8
      known ones (3-10) were isolated from the herb of Viola yedoensis. The structures
      of the new compounds were established by extensive spectroscopic means including
      1D ((1)H and (13)C) and 2D NMR experiments (HSQC, HMBC, and NOESY) as well as HR
      ESI-MS analysis. The absolute configurations of the known sesquiterpenes
      versicolactone B (3) and madolin W (6) were determined by a modified Mosher's
      method for the first time. The sesquiterpenes 1-3, and 5-9 exhibited anti
      complement activity against the classical pathway (CP) and the alternative
      pathway (AP) with the CH50 and AP50 values ranging from 0.14 to 0.37mg/mL and
      0.32 to 0.54mg/mL, respectively. Preliminary mechanism study using complement
      depleted sera showed that yedoensin A (1) and versicolactone B (3) acted on C1q,
      C3 and C9, while madolin W (6), aristoyunnolin E (7) and madolin Y (9) interacted
      with C1q, C3, C5 and C9 components in the complement activation cascade. 

PMID- 25562806
TI  - Metabolomic evaluation of ginsenosides distribution in Panax genus (Panax ginseng
      and Panax quinquefolius) using multivariate statistical analysis.
AB  - Ginseng is any one of the eleven species belonging to the genus Panax of the
      family Araliaceae and is found in North America and in eastern Asia. Ginseng is
      characterized by the presence of ginsenosides. Principally Panax ginseng and
      Panax quinquefolius are the adaptogenic herbs and are commonly distributed as
      health food markets. In the present study high performance liquid chromatography
      has been used to identify and quantify ginsenosides in the two subject species
      and the different parts of the plant (roots, neck, leaves, flowers, fruits). The
      power of this chromatographic technique to evaluate the identity of botanical
      material and to distinguishing different part of the plants has been investigated
      with metabolomic technique such as principal component analysis. Metabolomics
      provide a good opportunity for mining useful chemical information from the
      chromatographic data set resulting an important tool for quality evaluation of
      medicinal plants in the authenticity, consistency and efficacy. 

PMID- 25562807
TI  - Toxicity of fungal-generated silver nanoparticles to soil-inhabiting Pseudomonas
      putida KT2440, a rhizospheric bacterium responsible for plant protection and
      bioremediation.
AB  - Silver nanoparticles have attracted considerable attention due to their
      beneficial properties. But toxicity issues associated with them are also rising.
      The reports in the past suggested health hazards of silver nanoparticles at the
      cellular, molecular, or whole organismal level in eukaryotes. Whereas, there is
      also need to examine the exposure effects of silver nanoparticle to the microbes,
      which are beneficial to humans as well as environment. The available literature
      suggests the harmful effects of physically and chemically synthesised silver
      nanoparticles. The toxicity of biogenically synthesized nanoparticles has been
      less studied than physically and chemically synthesised nanoparticles. Hence,
      there is a greater need to study the toxic effects of biologically synthesised
      silver nanoparticles in general and mycosynthesized nanoparticles in particular.
      In the present study, attempts have been made to assess the risk associated with
      the exposure of mycosynthesized silver nanoparticles on a beneficial soil microbe
      Pseudomonas putida. KT2440. The study demonstrates mycosynthesis of silver
      nanoparticles and their characterisation by UV-vis spectrophotometry, FTIR, X-ray
      diffraction, nanosight LM20--a particle size distribution analyzer and TEM.
      Silver nanoparticles obtained herein were found to exert the hazardous effect at
      the concentration of 0.4 MUg/ml, which warrants further detailed investigations
      concerning toxicity.

PMID- 25562808
TI  - A new method for the determination of the nitrogen content of nitrocellulose
      based on the molar ratio of nitrite-to-nitrate ions released after alkaline
      hydrolysis.
AB  - A new method was proposed to determine the nitrogen content of nitrocelluloses
      (NCs). It is based on the finding of a linear relationship between the nitrogen
      content and the molar ratio of nitrite-to-nitrate ions released after alkaline
      hydrolysis. Capillary electrophoresis was used to monitor the concentration of
      nitrite and nitrate ions. The influences of hydrolysis time and molar mass of NC
      on the molar ratio of nitrite-to-nitrate ions were investigated, and new insights
      into the understanding of the alkaline denitration mechanism of NCs, underlying
      this analytical strategy is provided. The method was then tested successfully
      with various explosive and non-explosive NC-containing samples such as various
      daily products and smokeless gunpowders. Inherently to its principle exploiting a
      concentration ratio, this method shows very good repeatability in the
      determination of nitrogen content in real samples with relative standard
      deviation (n = 3) inferior to 1.5%, and also provides very significant advantages
      with respect to sample extraction, analysis time (1h for alkaline hydrolysis, 3
      min for electrophoretic separation), which was about 5 times shorter than for the
      classical Devarda's method, currently used in industry, and safety conditions (no
      need for preliminary drying NC samples, mild hydrolysis conditions with 1M sodium
      hydroxide for 1h at 60  degrees C).

PMID- 25562809
TI  - Electrokinetic removal of Cu and Zn in anaerobic digestate: interrelation between
      metal speciation and electrokinetic treatments.
AB  - In recent years, a potential controversy has arisen that whether the metal
      speciation in solid matrix determined its electrokinetic (EK) removal efficiency
      or by contrast. In present study, Cu and Zn in anaerobic digestate were selected
      as candidates to investigate the relation between the species of metal and EK
      treatment. The obtained results show that the removal efficiency for each
      fraction decreased in the order as follows: exchangeable >= bound to carbonates >
      bound to Fe-Mn oxides>bound to organic matters >> residual. For both Cu and Zn,
      their total removal performance was dependent on their dominant fraction in the
      digestate. A constant pH maintenance around the digestate via circulation of acid
      electrolyte is an optional operation because a strong acid atmosphere (pH < 2)
      around the digestate can be formed automatically as EK time elapses. Despite that
      many reactions occurred during EK process, the species distribution of Cu and Zn
      in the digestate determined their total EK removal efficiency essentially.

PMID- 25562810
TI  - Older people's conceptualization of abuse: a systematic review.
AB  - The concept of elder abuse is a relatively recent one, and there is ongoing
      debate around its definition and interpretation. Policy in America, the United
      Kingdom, and Ireland has been criticized as being professionally driven and
      therefore paternalistic and disempowering. Little is known about older people's
      understanding of the term "abuse" or the behaviors that they deem to be abusive.
      In this systematic review, eight databases were searched using agreed-upon
      criteria, and the results were assessed for relevance. Fifteen studies were
      included and are discussed under the themes of caregiving, domestic violence,
      society, abusive acts, and thresholds. 

PMID- 25562811
TI  - Enantioselective gold catalyzed dearomative [2+2]-cycloaddition between indoles
      and allenamides.
AB  - The highly enantioselective synthesis of densely functionalized 2,3-indoline
      cyclobutanes by means of chiral gold catalysis is presented. Intermolecular
      formal [2+2]-cycloaddition reactions between substituted indoles and allenamides
      enabled direct access to methylenecyclobutane-fused indolines, featuring two
      consecutive quaternary stereogenic centers with excellent stereochemical control
      (dr > 20 : 1, ee up to 99%). 

PMID- 25562812
TI  - Effect of Eclipta prostrata on lipid metabolism in hyperlipidemic animals.
AB  - Eclipta prostrata (Linn.) Linn. is a traditional Chinese medicine and has
      previously been reported to have hypolipidemic effects. However, its mechanism of
      action is not well understood. This study was conducted to identify the active
      fraction of Eclipta, its toxicity, its effect on hyperlipidemia, and its
      mechanism of action. The ethanol extract (EP) of Eclipta and fractions EPF1-EPF4,
      obtained by eluting with different concentrations of ethanol from a HPD-450
      macroporous resin column chromatography of the EP, were screened in
      hyperlipidemic mice for lipid-lowering activity, and EPF3 was the most active
      fraction. The LD50 of EPF3 was undetectable because no mice died with
      administration of EPF3 at 10.4 g/kg. Then, 48 male hamsters were used and
      randomly assigned to normal chow diet, high-fat diet, high-fat diet with
      Xuezhikang (positive control) or EPF3 (75, 150 and 250 mg/kg) groups. We
      evaluated the effects of EPF3 on body weight gain, liver weight gain, serum lipid
      concentration, antioxidant enzyme activity, and the expression of genes involved
      in lipid metabolism in hyperlipidemic hamsters. The results showed that EPF3
      significantly decreased body-weight gain and liver-weight gain and reduced the
      serum lipid levels in hyperlipidemic hamsters. EPF3 also increased the activities
      of antioxidant enzymes; up-regulated the mRNA expression of peroxisome
      proliferator-activated receptor alpha (PPARalpha), low density lipoprotein
      receptor (LDLR), lecithin-cholesterol transferase (LCAT) and scavenger receptor
      class B type Iota receptor (SR-BI); and down-regulated the mRNA expression of 3
      hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) in the liver. These results
      indicate that EPF3 ameliorates hyperlipidemia, in part, by reducing oxidative
      stress and modulating the transcription of genes involved in lipid metabolism.

PMID- 25562813
TI  - Impact of age on mean platelet volume and its relationship with coronary artery
      disease: a single-centre cohort study.
AB  - Elderly patients represent a high risk category among subjects with
      atherosclerosis, due to the presence of comorbidities and suboptimal response to
      antiplatelet drugs. Mean platelet volume (MPV) has been indicated as a marker of
      platelet reactivity, with contrasting data on its role on coronary artery
      disease. Aim of the present study was to evaluate the impact of age on the MPV
      and its role on the extent of coronary artery disease (CAD). METHODS: Our
      population is represented by a cohort of 3750 patients undergoing coronary
      angiography. Elderly were defined according to age >= 75 years. MPV was measured
      at admission. Significant coronary artery disease was defined as a stenosis >50%
      in at least 1 coronary vessel, while severe CAD was defined as left main and/or
      three-vessel disease. RESULTS: A total of 1170 out of 3750 (31.2%) patients were
      >= 75 years old. Advanced age was associated with female gender (p<0.001),
      hypertension (p<0.001), renal failure (p<0.001), previous myocardial infarction
      (p=0.03) coronary artery bypass grafting (p<0.001) indication to angiography
      (p<0.001), therapy with angiotension-receptor blockers, (p=0.003), nitrates,
      diuretics and calcium-antagonists (p<0.001), serum creatinine (p<0.001),
      fibrinogen (p<0.001) and C reactive protein (p=0.02), but inversely to
      percutaneous coronary interventions (p=0.02), dyslipidemia, family history of CAD
      and smoking (p<0.001, respectively), use of statins (p=0.02) and beta blockers
      (p=0.003), haemoglobin, total cholesterol and triglycerides (p<0.001,
      respectively), white blood cells (p=0.009) and platelet count (p=0.006). Elderly
      patients displayed a significantly larger platelet volume (p<0.001), with a
      direct linear relationship between age and the MPV (r=0.08, p<0.001), with age
      being confirmed as an independent predictor of larger MPV (>=10.85fl) at
      multivariate analysis (adjusted OR [95% CI]=1.18 [1.01-1.40], p=0.04). Among the
      elderly, MPV value above the median (>=10.85fl) was not associated with a higher
      prevalence of coronary artery disease (77.3 vs. 79.4%, p=0.39, adjusted OR [95%
      CI]=0.94 [0.66-1.33], p=0.71), or higher prevalence of severe CAD (35.2 vs.
      32.4%, p=0.28, adjusted OR [95% CI]=1.34 [0.99-1.82], p=0.06). CONCLUSION:
      Advanced age was directly associated with larger mean platelet volume that,
      however, did not contribute to explain the higher prevalence and extent of
      coronary artery disease observed in elderly patients.

PMID- 25562815
TI  - Integrated multi-scale strategies to investigate nutritional compounds and their
      effect on the gut microbiota.
AB  - A complex relationship occurs in the intestine between the gut microbiota, diet,
      and host. The modulation of the gut microbiota composition and activity is a
      target for health-promoting strategies and possible novel therapeutic approaches.
      Different in vitro and in vivo strategies have been applied to elucidate
      mechanisms or functions of dietary compounds on the gut microbiota, health, and
      physiology of human. Recent research has shown the potential of combining in
      vitro models and in vivo investigations within a coherent strategy. This review
      highlights recent developments and limits of in vitro gut fermentation and
      cellular models, gnotobiotic animals, and human trials. Combination of
      experimental scales is illustrated for resolving the complex mechanisms of
      dietary iron on gut microbiota, health, and infections. 

PMID- 25562814
TI  - Blunted hypertrophic response in old mouse muscle is associated with a lower
      satellite cell density and is not alleviated by resveratrol.
AB  - BACKGROUND: Sarcopenia contributes to the decreased quality of life in the older
      person. While resistance exercise is an effective measure to increase muscle mass
      and strength, the hypertrophic response may be blunted in old age. OBJECTIVES: To
      determine 1) whether hypertrophy in the m. plantaris of old mice was blunted
      compared to adult and 2) whether this was related to a reduced satellite cell
      (SC) density and 3) how resveratrol affects hypertrophy in old mice. METHODS: In
      adult (7.5 months, n=11), old (23.5 months, n=10) and old-resveratrol-treated
      (n=10) male C57BL/6J mice, hypertrophy of the left m. plantaris was induced by
      denervation of its synergists. The contralateral leg served as control. RESULTS:
      After six weeks, overload-induced myofiber hypertrophy and IIB-IIA shift in
      myofiber type composition were less pronounced in old than adult mice (P=0.03),
      irrespective of resveratrol treatment. Muscles from old mice had a lower SC
      density than adult muscles (P=0.002). Overload-induced SC proliferation (P<0.05)
      resulted in an increased SC density in old, but not adult muscles (P=0.02), while
      a decrease occurred after resveratrol supplementation (P=0.044). Id2 and myogenin
      protein expression levels were higher in old than adult muscles (P<0.05). Caspase
      3 was expressed more in hypertrophied than control muscles and was reduced with
      resveratrol (P<0.05). CONCLUSION: The blunted hypertrophic response in old mice
      was associated with a lower SC density, but there was no evidence for a lower
      capacity for proliferation. Resveratrol did not rescue the hypertrophic response
      and even reduced, rather than increased, the number of SCs in hypertrophied
      muscles.

PMID- 25562816
TI  - High-value products from plants: the challenges of process optimization.
AB  - Plants can be used to produce a diverse repertoire of complex small-molecule
      compounds and recombinant proteins that are valuable as industrial and
      pharmaceutical products. But as we move from proof-of-principle experiments and
      begin to consider the realistic prospects of commercial production, the focus
      must shift from the achievement of target molecule production and move towards
      quality, purity and yield aspects that determine commercial feasibility. This
      review describes some of the recent advances that have been implemented to
      improve the development of integrated production processes for high-value
      molecules expressed in plants, including the introduction of novel procedures to
      increase the likelihood of regulatory acceptance. 

PMID- 25562817
TI  - Leukocyte common antigen (CD45) negative follicular lymphoma, a rare
      immunophenotypic presentation.
AB  - BACKGROUND: CD45 is universally expressed on nucleated hematopoietic cells in
      healthy individuals with variable intensities. Although down-regulation of CD45
      expression is commonly seen in immature B-cell neoplasm, loss of CD45 expression
      is rarely observed in mature B-cell lymphoproliferative disorders. CASE REPORT: A
      64-y old man was presented with fatigue and night sweat in July 2013. Physical
      examination revealed right axillary lymphadenopathy without splenohepatomegaly.
      The lymph node was sent for flow cytometry and histomorphologic evaluation. Flow
      cytometric analysis revealed the presence of CD45+ and CD45- cell populations.
      The CD45+ population (42%) comprised mainly unremarkable CD3+ T cells. However,
      the CD45- population (35%) showed CD19+, CD20+, and CD10+ immunophenotype with
      monotypic surface Lambda immunoglobulin light chain expression.
      Immunohistochemical studies performed on tissue section revealed that neoplastic
      lymphoid nodules were positive for CD20, BCL-6 and BCL-2 with low proliferation
      index by Ki-67 staining, but again negative for CD45. FISH analysis confirmed the
      presence of IGH/BCL2 rearrangement. Follicular lymphoma (grade 1) with negative
      CD45 expression was diagnosed. CONCLUSIONS: Loss of CD45 expression has been
      reported, but all cases documented were large B cell lymphoma (LBCL). To the best
      of our knowledge, this is the first case of low grade follicular lymphoma with
      lack of CD45 expression. We report this case because of not only its rarity but
      also to raise awareness that loss of CD45 expression can occur in LBCL as well as
      in low grade B-cell lymphomas.

PMID- 25562818
TI  - Clinical relevance of erythrocyte ferritin in microcytic anemias.
AB  - BACKGROUND: Erythrocyte ferritin (EF) reflects the balance between iron supply
      and its utilization for hemoglobin synthesis. This balance is altered in
      microcytosis. We aimed to evaluate the diagnostic value of both EF and the ratio
      (FRR) plasma ferritin (PF)/EF in these disorders. METHODS: A total of 231
      subjects participated in the study. Samples from 93 adult patients with different
      causes of microcytosis, 57 healthy subjects and 81 full-term newborns were
      analyzed to determine EF and PF concentrations and other hematological
      parameters. RESULTS: In patients with iron deficiency, and in contrast to PF, EF
      decreased only in the presence of anemia and in direct correlation with the
      degree of microcytosis (Pearson's p<0.001). EF values for thalassemia patients
      were higher than those observed in controls (p<10e-5), while PF concentrations
      were similar between these groups. This EF increase was more marked in the delta
      beta thalassemia group (p<0.05). Finally, FRR was much higher in patients with
      anemia of inflammation than in those with thalassemia (p<10e-5), thus helping to
      discriminate between these disorders. CONCLUSIONS: EF and FRR are tools that may
      be useful in the diagnosis of the main causes of microcytosis.

PMID- 25562819
TI  - Serum CD166: a novel hepatocellular carcinoma tumor marker.
AB  - BACKGROUND: We evaluated the diagnostic value of serum-CD166 in patients with
      hepatocellular carcinoma (HCC). METHODS: Tissue-CD166 was measured using
      immunohistochemistry. Cell proliferation and migration were evaluated using MTT
      and Transwell assays, respectively. Serum-CD166 was examined using ELISA and
      western blotting. RESULTS: CD166 was up-regulated in HCC compared to those in
      normal liver tissues. Cell proliferation was positively correlated and cell
      migration was negatively correlated with endogenous CD166 expression in HCC
      cells. CD166 inhibition using specific shRNA decreased cell proliferation but
      increased cell migration. Serum CD166 concentrations were much higher in HCC than
      in colon cancer, hepatitis B, hepatitis C, cirrhosis, gastric cancer, breast
      cancer, lung cancer and healthy individuals. Serum CD166 also decreased
      dramatically after curative surgery. A positive correlation was found between
      serum CD166 and AFP (R=0.7141, p=0.000). Serum CD166 was also positively
      correlated with gamma-GT, bile acid, ALT, AST, and ALP but was negatively
      correlated with Alb and pre-Alb. The area under the receiver operating
      characteristic curve for serum-CD166 was 0.9860, which was better than AFP (AUC
      ROC, 0.9354) for the differentiation of HCC patients from healthy individuals,
      with a cut-off of 261 ng/ml (sensitivity: 100.00%, specificity: 89.41%).
      CONCLUSION: Serum CD166 is a novel diagnostic tumor marker for HCC.

PMID- 25562822
TI  - Electrophysiological evidence for retrieval mode immediately after a task switch.
AB  - It has been suggested that retrieving episodic information can involve adopting a
      cognitive state or set: retrieval mode. In a series of studies, an event-related
      potential (ERP) index of retrieval mode has been identified in designs which cue
      participants on a trial-by-trial basis to switch between preparing for and then
      completing an episodic or non-episodic retrieval task. However, a confound in
      these studies is that along with task type the content of what is to be retrieved
      has varied. Here we examined whether the ERP index of retrieval mode remains when
      the contents of an episodic and non-episodic task are highly similar - both
      requiring a location judgement. In the episodic task participants indicated the
      screen location where words had been shown in a prior study phase
      (left/right/new); whereas in the perceptual task they indicated the current
      screen location of the word (top/middle/bottom). Consistent with previous studies
      the ERPs elicited while participants prepared for episodic retrieval were more
      positive-going at right-frontal sites than when they prepared for the perceptual
      task. This index was observed, however, on the first trial after participants had
      switched tasks, rather than on the second trial, as has been observed previously.
      Potential reasons for this are discussed, including the critical manipulation of
      similarity in contents between tasks, as well as the use of a predictable cue
      sequence. 

PMID- 25562820
TI  - Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and human
      cancer cells.
AB  - Cyclin-dependent kinases 4 and 6 (CDK4/6) in complex with D-type cyclins promote
      cell cycle entry. Most human cancers contain overactive CDK4/6-cyclin D, and
      CDK4/6-specific inhibitors are promising anti-cancer therapeutics. Here, we
      investigate the critical functions of CDK4/6-cyclin D kinases, starting from an
      unbiased screen in the nematode Caenorhabditis elegans. We found that
      simultaneous mutation of lin-35, a retinoblastoma (Rb)-related gene, and fzr-1,
      an orthologue to the APC/C co-activator Cdh1, completely eliminates the essential
      requirement of CDK4/6-cyclin D (CDK-4/CYD-1) in C. elegans. CDK-4/CYD-1
      phosphorylates specific residues in the LIN-35 Rb spacer domain and FZR-1 amino
      terminus, resembling inactivating phosphorylations of the human proteins. In
      human breast cancer cells, simultaneous knockdown of Rb and FZR1 synergistically
      bypasses cell division arrest induced by the CDK4/6-specific inhibitor PD
      0332991. Our data identify FZR1 as a candidate CDK4/6-cyclin D substrate and
      point to an APC/C(FZR1) activity as an important determinant in response to
      CDK4/6-inhibitors. 

PMID- 25562821
TI  - Content-specific evidence accumulation in inferior temporal cortex during
      perceptual decision-making.
AB  - During a perceptual decision, neuronal activity can change as a function of time
      integrated evidence. Such neurons may serve as decision variables, signaling a
      choice when activity reaches a boundary. Because the signals occur on a
      millisecond timescale, translating to human decision-making using functional
      neuroimaging has been challenging. Previous neuroimaging work in humans has
      identified patterns of neural activity consistent with an accumulation account.
      However, the degree to which the accumulating neuroimaging signals reflect
      specific sources of perceptual evidence is unknown. Using an extended face/house
      discrimination task in conjunction with cognitive modeling, we tested whether
      accumulation signals, as measured using functional magnetic resonance imaging
      (fMRI), are stimulus-specific. Accumulation signals were defined as a change in
      the slope of the rising edge of activation corresponding with response time (RT),
      with higher slopes associated with faster RTs. Consistent with an accumulation
      account, fMRI activity in face- and house-selective regions in the inferior
      temporal cortex increased at a rate proportional to decision time in favor of the
      preferred stimulus. This finding indicates that stimulus-specific regions perform
      an evidence integrative function during goal-directed behavior and that different
      sources of evidence accumulate separately. We also assessed the decision-related
      function of other regions throughout the brain and found that several regions
      were consistent with classifications from prior work, suggesting a degree of
      domain generality in decision processing. Taken together, these results provide
      support for an integration-to-boundary decision mechanism and highlight possible
      roles of both domain-specific and domain-general regions in decision evidence
      evaluation. 

PMID- 25562823
TI  - On self-feedback connectivity in neural mass models applied to event-related
      potentials.
AB  - Neural mass models (NMMs) applied to neuroimaging data often do not emphasise
      intrinsic self-feedback within a neural population. However, based on mean-field
      theory, any population of coupled neurons is intrinsically endowed with effective
      self-coupling. In this work, we examine the effectiveness of three cortical NMMs
      with different self-feedbacks using a dynamic causal modelling approach.
      Specifically, we compare the classic Jansen and Rit (1995) model (no self
      feedback), a modified model by Moran et al. (2007) (only inhibitory self
      feedback), and our proposed model with inhibitory and excitatory self-feedbacks.
      Using bifurcation analysis, we show that single-unit Jansen-Rit model is less
      robust in generating oscillatory behaviour than the other two models. Next, under
      Bayesian inversion, we simulate single-channel event-related potentials (ERPs)
      within a mismatch negativity auditory oddball paradigm. We found fully self
      feedback model (FSM) to provide the best fit to single-channel data. By analysing
      the posterior covariances of model parameters, we show that self-feedback
      connections are less sensitive to the generated evoked responses than the other
      model parameters, and hence can be treated analogously to "higher-order"
      parameter corrections of the original Jansen-Rit model. This is further supported
      in the more realistic multi-area case where FSM can replicate data better than
      JRM and MoM in the majority of subjects by capturing the finer features of the
      ERP data more accurately. Our work informs how NMMs with full self-feedback
      connectivity are not only more consistent with the underlying neurophysiology,
      but can also account for more complex features in ERP data. 

PMID- 25562824
TI  - Striatal D1 and D2 signaling differentially predict learning from positive and
      negative outcomes.
AB  - The extent to which we learn from positive and negative outcomes of decisions is
      modulated by the neurotransmitter dopamine. Dopamine neurons burst fire in
      response to unexpected rewards and pause following negative outcomes. This dual
      signaling mechanism is hypothesized to drive both approach and avoidance
      behavior. Here we test a prediction deriving from a computational reinforcement
      learning model, in which approach is mediated via activation of the direct
      cortico-striatal pathway due to striatal D1 receptor stimulation, while avoidance
      occurs via disinhibition of indirect pathway striatal neurons secondary to a
      reduction of D2 receptor stimulation. Using positron emission tomography with two
      separate radioligands, we demonstrate that individual differences in human
      approach and avoidance learning are predicted by variability in striatal D1 and
      D2 receptor binding, respectively. Moreover, transient dopamine precursor
      depletion improved learning from negative outcomes. These findings support a
      bidirectional modulatory role for striatal dopamine in reward and avoidance
      learning via segregated D1 and D2 cortico-striatal pathways. 

PMID- 25562825
TI  - Early visual deprivation changes cortical anatomical covariance in dorsal-stream
      structures.
AB  - Early blind individuals possess thicker occipital cortex compared to sighted
      ones. Occipital cortical thickness is also predictive of performance on several
      auditory discrimination tasks in the blind, which suggests that it can serve as a
      neuroanatomical marker of auditory behavioural abilities. In light of this
      atypical relationship between occipital thickness and auditory function, we
      sought to investigate here the covariation of occipital cortical morphology in
      occipital areas with that of all other areas across the cortical surface, to
      assess whether the anatomical covariance with the occipital cortex differs
      between early blind and sighted individuals. We observed a reduction in
      anatomical covariance between the right occipital cortex and several areas of the
      visual dorsal stream in a group of early blind individuals relative to sighted
      controls. In a separate analysis, we show that the performance of the early blind
      in a transposed melody discrimination task was strongly predicted by the strength
      of the cortical covariance between the occipital cortex and intraparietal sulcus,
      a region for which cortical thickness in the sighted was previously shown to
      predict performance in the same task. These findings therefore constitute the
      first evidence linking altered anatomical covariance to early sensory
      deprivation. Moreover, since covariation of cortical morphology could potentially
      be related to anatomical connectivity or driven by experience-dependent
      plasticity, it could consequently help guide future functional connectivity and
      diffusion tractography studies. 

PMID- 25562826
TI  - Brain activity modulation during the production of imperative and declarative
      pointing.
AB  - Pointing is a communicative gesture, commonly used for expressing two main
      intentions: imperative, to obtain a desired object/action from the other, or
      declarative, to share attention/interest about a referent with the other.
      Previous neuroimaging research on adults examined pointing almost exclusively as
      a reaching-like motor act rather than as a communicative gesture. Here, we used
      fMRI to record brain activity while 16 participants produced either imperative or
      declarative pointing gestures within a communicative context. A network of
      regions (the bilateral ventral premotor cortex, anterior midcingulate cortex,
      middle insula and the right preSMA) showed a preference for the production of
      declarative pointing as opposed to imperative pointing. The right preSMA also
      preferred declarative intention during pointing observation. Instead,
      independently from the intention, the right pMTG was more active during pointing
      observation than production. In the bilateral posterior parietal reach region we
      also observed a side (contra>ipsi) effect when the intention was imperative,
      regardless of the subject's role in the communication. Based on these results, we
      propose that pointing with declarative intention recruits a network of regions
      associated with will, motivation, emotional/affective expression and
      intersubjectivity, whereas pointing with imperative intention recruits regions
      associated with reaching. The proposal is consistent with the developmental
      hypothesis that declarative pointing reflects social cognitive abilities more
      than imperative pointing and establishes a stimulating link for future
      interdisciplinary research. 

PMID- 25562827
TI  - What it means to be Zen: marked modulations of local and interareal
      synchronization during open monitoring meditation.
AB  - Experienced meditators are able to voluntarily modulate their state of
      consciousness and attention. In the present study, we took advantage of this
      ability and studied brain activity related to the shift of mental state.
      Electrophysiological activity, i.e. EEG, was recorded from 11 subjects with
      varying degrees of meditation experience during Zen meditation (a form of open
      monitoring meditation) and during non-meditation rest. On a behavioral level,
      mindfulness scores were assessed using the Mindfulness Attention and Awareness
      Scale (MAAS). Analysis of EEG source power revealed the so far unreported finding
      that MAAS scores significantly correlated with gamma power (30-250Hz),
      particularly high-frequency gamma (100-245Hz), during meditation. High levels of
      mindfulness were related to increased high-frequency gamma, for example, in the
      cingulate cortex and somatosensory cortices. Further, we analyzed the
      relationship between connectivity during meditation and self-reported mindfulness
      (MAAS). We found a correlation between graph measures in the 160-170Hz range and
      MAAS scores. Higher levels of mindfulness were related to lower small worldedness
      as well as global and local clustering in paracentral, insular, and thalamic
      regions during meditation. In sum, the present study shows significant
      relationships of mindfulness and brain activity during meditation indicated by
      measures of oscillatory power and graph theoretical measures. The most prominent
      effects occur in brain structures crucially involved in processes of awareness
      and attention, which also show structural changes in short- and long-term
      meditators, suggesting continuative alterations in the meditating brain. Overall,
      our study reveals strong changes in ongoing oscillatory activity as well as
      connectivity patterns that appear to be sensitive to the psychological state
      changes induced by Zen meditation. 

PMID- 25562829
TI  - Deep convolutional neural networks for multi-modality isointense infant brain
      image segmentation.
AB  - The segmentation of infant brain tissue images into white matter (WM), gray
      matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying
      early brain development in health and disease. In the isointense stage
      (approximately 6-8 months of age), WM and GM exhibit similar levels of intensity
      in both T1 and T2 MR images, making the tissue segmentation very challenging.
      Only a small number of existing methods have been designed for tissue
      segmentation in this isointense stage; however, they only used a single T1 or T2
      images, or the combination of T1 and T2 images. In this paper, we propose to use
      deep convolutional neural networks (CNNs) for segmenting isointense stage brain
      tissues using multi-modality MR images. CNNs are a type of deep models in which
      trainable filters and local neighborhood pooling operations are applied
      alternatingly on the raw input images, resulting in a hierarchy of increasingly
      complex features. Specifically, we used multi-modality information from T1, T2,
      and fractional anisotropy (FA) images as inputs and then generated the
      segmentation maps as outputs. The multiple intermediate layers applied
      convolution, pooling, normalization, and other operations to capture the highly
      nonlinear mappings between inputs and outputs. We compared the performance of our
      approach with that of the commonly used segmentation methods on a set of manually
      segmented isointense stage brain images. Results showed that our proposed model
      significantly outperformed prior methods on infant brain tissue segmentation. In
      addition, our results indicated that integration of multi-modality images led to
      significant performance improvement. 

PMID- 25562831
TI  - Attenuation of lysozyme amyloid cytotoxicity by SPION-mediated modulation of
      amyloid aggregation.
AB  - The formation and deposition of proteinaceous aggregates of amyloid fibrils
      characterize diverse degenerative diseases, such as Alzheimer's, Parkinson's, and
      systemic amyloidosis. The presence of these aggregates is associated with
      clinical manifestations, and various forms of amyloid aggregates have been
      identified to be cytotoxic. Although the exact mechanism of amyloid toxicity
      remains to be elucidated, prevention of amyloid fibril formation and aggregation
      forms a possible therapeutic approach. Nanomaterials possess the potential for
      such a strategy. Using hen egg white lysozyme (HEWL) as a prototypic amyloid
      forming protein, we found a reduction in the aggregation rate of HEWL in the
      presence of super-paramagnetic iron oxide nanoparticles (SPIONs) with slowing of
      nucleation and amyloid fibril elongation. HEWL-amyloid had a predominantly
      fibrillar structure and was toxic to various cells. A significant attenuation of
      cytotoxicity was observed when cells were treated with SPION-interacted HEWL
      amyloid. Ultra-structural differences were observed between the native and SPION
      interacted HEWL-amyloids by SEM and TEM imaging. Our findings confirm that SPIONs
      perturb amyloid fibrillation, thereby reducing the cytotoxicity of amyloid. 

PMID- 25562828
TI  - A critical role of the human hippocampus in an electrophysiological measure of
      implicit memory.
AB  - The hippocampus has traditionally been thought to be critical for conscious
      explicit memory but not necessary for unconscious implicit memory processing. In
      a recent study of a group of mild amnesia patients with evidence of MTL damage
      limited to the hippocampus, subjects were tested on a direct test of item
      recognition confidence while electroencephalogram (EEG) was acquired, and
      revealed intact measures of explicit memory from 400 to 600 ms (mid-frontal old
      new effect, FN400). The current investigation re-analyzed this data to study
      event-related potentials (ERPs) of implicit memory, using a recently developed
      procedure that eliminated declarative memory differences. Prior ERP findings from
      this technique were first replicated in two independent matched control groups,
      which exhibited reliable implicit memory effects in posterior scalp regions from
      400 to 600 ms, which were topographically dissociated from the explicit memory
      effects of familiarity. However, patients were found to be dramatically impaired
      in implicit memory effects relative to control subjects, as quantified by a
      reliable condition * group interaction. Several control analyses were conducted
      to consider alternative factors that could account for the results, including
      outliers, sample size, age, or contamination by explicit memory, and each of
      these factors was systematically ruled out. Results suggest that the hippocampus
      plays a fundamental role in aspects of memory processing that are beyond
      conscious awareness. The current findings therefore indicate that both memory
      systems of implicit and explicit memory may rely upon the same neural structures 
      but function in different physiological ways.

PMID- 25562832
TI  - Adsorption of chromium from aqueous solutions using crosslinked chitosan
      diethylenetriaminepentaacetic acid.
AB  - Chitosan (CH) and its derivatives have been the focus of attention for
      researchers as potential adsorbents for heavy metal removal. The adsorption
      potential of chitosan cross-linked with diethylenetriaminepentaacetic acid (CD)
      for Cr6+ was investigated. CD was characterized by FTIR, XRD, TGA, XPS and ESR
      techniques. Batch experiments were conducted to optimize the parameters affecting
      the adsorption of chromium. The optimum pH was found to be 3 and the adsorption
      process was found to be exothermic. Adsorption isotherms were determined and the
      maximum adsorption capacity of CD for chromium was found to be 192.3 mg/g which
      was higher than the adsorption capacity of the adsorbents reported in literature.
      The thermodynamic parameters, such as Gibbs free energy, changes in enthalpy and
      changes in entropy change were also evaluated. XPS and ESR studies revealed that
      Cr6+ adsorbed onto CD was reduced to Cr3+. The efficacy of CD for removal of Cr6+
      from chrome plating effluent was demonstrated.

PMID- 25562830
TI  - Rhythmic 3-4Hz discharge is insufficient to produce cortical BOLD fMRI decreases
      in generalized seizures.
AB  - Absence seizures are transient episodes of impaired consciousness accompanied by
      3-4 Hz spike-wave discharge on electroencephalography (EEG). Human functional
      magnetic resonance imaging (fMRI) studies have demonstrated widespread cortical
      decreases in the blood oxygen-level dependent (BOLD) signal that may play an
      important role in the pathophysiology of these seizures. Animal models could
      provide an opportunity to investigate the fundamental mechanisms of these
      changes, however they have so far failed to consistently replicate the cortical
      fMRI decreases observed in human patients. This may be due to important
      differences between human seizures and animal models, including a lack of
      cortical development in rodents or differences in the frequencies of rodent (7-8
      Hz) and human (3-4 Hz) spike-wave discharges. To examine the possible
      contributions of these differences, we developed a ferret model that exhibits 3-4
      Hz spike-wave seizures in the presence of a sulcated cortex. Measurements of BOLD
      fMRI and simultaneous EEG demonstrated cortical fMRI increases during and
      following spike-wave seizures in ferrets. However unlike human patients,
      significant fMRI decreases were not observed. The lack of fMRI decreases was
      consistent across seizures of different durations, discharge frequencies, and
      anesthetic regimes, and using fMRI analysis models similar to human patients. In
      contrast, generalized tonic-clonic seizures under the same conditions elicited
      sustained postictal fMRI decreases, verifying that the lack of fMRI decreases
      with spike-wave was not due to technical factors. These findings demonstrate that
      3-4 Hz spike-wave discharge in a sulcated animal model does not necessarily
      produce fMRI decreases, leaving the mechanism for this phenomenon open for
      further investigation.

PMID- 25562834
TI  - Mismatch negativity (MMN) deficiency: a break-through biomarker in predicting
      psychosis onset.
AB  - Currently, the mismatch negativity (MMN) deficit is one of the most robust and
      replicable findings in schizophrenia, reflecting cognitive and functional
      decline, psychosocial and socio-occupational impairment, and executive
      dysfunction in these patients. An important break-through has very recently taken
      place here in the prediction of conversion to psychosis when the MMN in
      particular to change in tone duration was recorded in clinically at risk-mental
      state (ARMS) individuals. Attenuations in the MMN in these patients may be very
      useful in helping clinicians determine who are most likely to develop a psychotic
      disorder, as we will review in the present article. 

PMID- 25562833
TI  - Hemifield-dependent N1 and event-related theta/delta oscillations: An unbiased
      comparison of surface Laplacian and common EEG reference choices.
AB  - Surface Laplacian methodology has been used to reduce the impact of volume
      conduction and arbitrary choice of EEG recording reference for the analysis of
      surface potentials. However, the empirical implications of employing these
      different transformations to the same EEG data remain obscure. This study
      directly compared the statistical effects of four commonly-used (nose, linked
      mastoids, average) or recommended (reference electrode standardization technique
      [REST]) references and their spherical spline current source density (CSD)
      transformation for a large data set stemming from a well-understood experimental
      manipulation. ERPs (72 sites) recorded from 130 individuals during a visual half
      field paradigm with highly-controlled emotional stimuli were characterized by mid
      parietooccipital N1 (125 ms peak latency) and event-related synchronization (ERS)
      of theta/delta (160 ms), which were most robust over the contralateral
      hemisphere. All five data transformations were rescaled to the same covariance
      and submitted to a single temporal or time-frequency PCA (Varimax) to yield
      simplified estimates of N1 or theta/delta ERS. Unbiased nonparametric permutation
      tests revealed that these hemifield-dependent asymmetries were by far most focal
      and prominent for CSD data, despite all transformations showing maximum effects
      at mid-parietooccipital sites. Employing smaller subsamples (signal-to-noise) or
      window-based ERP/ERS amplitudes did not affect these comparisons. Furthermore,
      correlations between N1 and theta/delta ERS at these sites were strongest for CSD
      and weakest for nose-referenced data. Contrary to the common notion that the
      spatial high pass filter properties of a surface Laplacian reduce important
      contributions of neuronal generators to the EEG signal, the present findings
      demonstrate that instead volume conduction inherent in surface potentials weakens
      the representation of neuronal activation patterns at scalp that directly reflect
      regional brain activity.

PMID- 25562835
TI  - Copper exposure induces toxicity to the antioxidant system via the destruction of
      Nrf2/ARE signaling and caspase-3-regulated DNA damage in fish muscle:
      amelioration by myo-inositol.
AB  - The muscle is the main portion of fish that is consumed by humans. Copper (Cu)
      can induce oxidative damage in fish muscle. However, the effects of Cu exposure
      on the muscle antioxidant system and molecular patterns and preventive measures
      against these effects remain unclear. In this study, ROS production, enzymatic
      and mRNA levels of antioxidant enzymes and NF-E2-related factor 2 (Nrf2)
      signaling-related molecules, antioxidant response element (ARE) binding ability,
      DNA fragmentation and caspase-3 activities were analyzed in fish muscle following
      Cu exposure or myo-inositol (MI) pre-administration. The results indicated that
      contamination due to copper exposure caused an approximately three-fold increase
      in ROS production, induced lipid peroxidation and protein oxidation, and resulted
      in depletion of the glutathione (GSH) content of fish muscle. Moreover, Cu
      exposure caused decreases in the activities of total superoxide dismutase (T
      SOD), CuZnSOD, and glutathione peroxidase (GPx) that were accompanied by
      decreases in CuZnSOD, GPx1a, GPx1b and signaling factor protein kinase C delta
      mRNA levels. The decreases in the antioxidant enzyme gene mRNA levels were
      confirmed to be partly due to the reduced nuclear Nrf2 protein levels, poor ARE
      binding ability and increased caspase-3 signaling-modulated DNA fragmentation in
      the fish muscle. Interestingly, MI pre-treatment prevented fish muscle from Cu
      induced oxidative damages mainly through increasing the GSH content, and
      increasing the CuZnSOD and GPx activities and corresponding mRNA levels and ARE
      binding ability. Taken together, our results show for the first time that Cu
      exposure caused oxidative damage to the muscle by decreasing the antioxidant
      enzyme activities via the down-regulation of the expression of genes related to
      the disruption of the Nrf2/ARE signaling, and this down-regulation was partially
      caused by caspase-3-regulated DNA fragmentation. Finally, MI protects fish
      against Cu toxicity. 

PMID- 25562836
TI  - Heparin inhibits the inflammatory response induced by LPS and HMGB1 by blocking
      the binding of HMGB1 to the surface of macrophages.
AB  - High mobility group box 1 protein (HMGB1), a nuclear non-histone DNA-binding
      protein, is secreted extracellularly during inflammation and is a late mediator
      of inflammatory responses. The pro-inflammatory activity of recombinant HMGB1
      proteins is dependent upon the formation of complexes with other mediators, such
      as lipopolysaccharide (LPS). This study investigated the influence of heparin on
      LPS+HMGB1-mediated inflammatory responses in cultured macrophages and a murine
      sepsis model. HMGB1 promoted the phosphorylation of p38 and ERK1/2. HMGB1
      enhanced the induction of the pro-inflammatory cytokine, TNF-alpha, by LPS in
      macrophages. Heparin blocked the binding of HMGB1 to the surface of macrophages,
      and suppressed the phosphorylation of p38 and ERK1/2, but not JNK; TNF-alpha
      secretion was also decreased. However, heparin alone did not affect LPS-induced
      production of TNF-alpha. Heparin reduced lethality in mice exposed to LPS+HMGB1.
      To conclude, heparin inhibited LPS-induced HMGB1-amplified inflammatory responses
      by blocking HMGB1 binding to macrophage surfaces. Heparin could be used
      therapeutically as an effective inhibitor of HMGB1-associated inflammation. 

PMID- 25562837
TI  - Is culling dogs really necessary for echinococcosis control?

PMID- 25562838
TI  - Exploring the lived experience of adults using prescription opioids to manage
      chronic noncancer pain.
AB  - BACKGROUND: Chronic noncancer pain (CNCP) and prescription opioid use is a highly
      complex and growing health care issue in Canada. Many quantitative research
      studies have investigated the effectiveness of opioids for chronic pain; however,
      gaps remain in the literature regarding the personal experience of using opioids
      and their impact on those experiencing CNCP. OBJECTIVE: To explore the lived
      experience of adults using prescription opioids to manage CNCP, focusing on how
      opioid medication affected their daily lives. METHODS: In-depth qualitative
      interviews were conducted with nine adults between 40 and 68 years of age who
      were using prescription opioids daily for CNCP. Interviews were audiorecorded and
      transcribed, and subsequently analyzed using interpretive phenomenological
      analysis. RESULTS: Six major themes identified positive and negative aspects of
      opioid use associated with social, physical, emotional and psychological
      dimensions of pain management. These themes included the process of decision
      making, and physical and psychosocial consequences of using opioids including
      pharmacological side effects, feeling stigmatized, guilt, fears, ambivalence,
      self-protection and acceptance. CONCLUSION: Although there were many negative
      aspects to using opioids daily, the positive effects outweighed the negative for
      most participants and most of the negative aspects were socioculturally induced
      rather than caused by the drug itself. The present study highlighted the
      complexities involved in using prescription opioids daily for management of CNCP
      for individuals living with pain.

PMID- 25562840
TI  - Fast photodynamics of azobenzene probed by scanning excited-state potential
      energy surfaces using slow spectroscopy.
AB  - Azobenzene, a versatile and polymorphic molecule, has been extensively and
      successfully used for photoswitching applications. The debate over its
      photoisomerization mechanism leveraged on the computational scrutiny with ever
      increasing levels of theory. However, the most resolved absorption spectrum for
      the transition to S1(npi*) has not followed the computational advances and is
      more than half a century old. Here, using jet-cooled molecular beam and
      multiphoton ionization techniques we report the first high-resolution spectra of
      S1(npi*) and S2(pipi*). The photophysical characterization reveals directly the
      structural changes upon excitation and the timescales of dynamical processes. For
      S1(npi*), we find that changes in the hybridization of the nitrogen atoms are the
      driving force that triggers isomerization. In combination with quantum chemical
      calculations we conclude that photoisomerization occurs along an inversion
      assisted torsional pathway with a barrier of ~2 kcal mol(-1). This methodology
      can be extended to photoresponsive molecular systems so far deemed non-accessible
      to high-resolution spectroscopy.

PMID- 25562839
TI  - Denial of pain medication by health care providers predicts in-hospital illicit
      drug use among individuals who use illicit drugs.
AB  - BACKGROUND: Undertreated pain is common among people who use illicit drugs
      (PWUD), and can often reflect the reluctance of health care providers to provide
      pain medication to individuals with substance use disorders. OBJECTIVE: To
      investigate the relationship between having ever been denied pain medication by a
      health care provider and having ever reported using illicit drugs in hospital.
      METHODS: Data were derived from participants enrolled in two Canadian prospective
      cohort studies between December 2012 and May 2013. Using bivariable and
      multivariable logistic regression analyses, the relationship between having ever
      been denied pain medication by a health care provider and having ever reported
      using illicit drugs in hospital was examined. RESULTS: Among 1053 PWUD who had
      experienced >= 1 hospitalization, 452 (44%) reported having ever used illicit
      drugs while in hospital and 491(48%) reported having ever been denied pain
      medication. In a multivariable model adjusted for confounders, having been denied
      pain medication was positively associated with having used illicit drugs in
      hospital (adjusted OR 1.46 [95% CI 1.14 to 1.88]). CONCLUSIONS: The results of
      the present study suggest that the denial of pain medication is associated with
      the use of illicit drugs while hospitalized. These findings raise questions about
      how to appropriately manage addiction and pain among PWUD and indicate the
      potential role that harm reduction programs may play in hospital settings.

PMID- 25562841
TI  - Dopaminergic function and intertemporal choice.
AB  - The discounting of delayed rewards, also known as temporal or delay discounting,
      is intrinsic to everyday decisions and can be impaired in pathological states
      such as addiction disorders. Preclinical and human studies suggest a role for
      dopaminergic function in temporal discounting but this relationship has not yet
      been verified using molecular imaging of the living human brain. Here, we
      evaluated dopaminergic function in temporal discounting using positron emission
      tomography (PET) with two different dopaminergic ligands assessing three
      populations in whom temporal discounting has been shown to be impaired. First, we
      show using [11C]raclopride PET that in pathological gamblers, greater temporal
      discounting correlates with decreased ventral striatal binding potential,
      convergent with translational findings of lower nucleus accumbens D2/D3 receptor
      density in high-impulsive rodents. Temporal discounting also correlates with
      lower ventral striatal dopamine release in response to high-reward magnitude
      suggesting that dopamine-mediated devaluation of larger delayed rewards may drive
      choice preferences. Second, we show using [18F]fluorodopa PET that in Parkinson's
      disease, temporal discounting correlates with greater left caudate dopaminergic
      terminal function. Finally, in subjects with Parkinson's disease and dopamine
      medication-induced behavioral addictions, temporal discounting is further
      correlated with greater dopaminergic terminal function in the anterior putamen.
      These findings provide insights into the relationship between striatal dopamine
      function and temporal discounting, and its potential role in pathological
      disorders and mechanisms underlying treatment interventions. 

PMID- 25562844
TI  - Physicochemical and crystal structure analysis of pranlukast pseudo-polymorphs I:
      anhydrates and hydrate.
AB  - Pranlukast (PRS) is a leukotriene receptor antagonist for the treatment of
      bronchial asthma. Pranlukast is formulated as a hemihydrate (HH) form in the drug
      product. Here, we report three new anhydrate forms of PRS (AH, form I-III). These
      polymorphs and PRS HH were characterized by PXRD, TG-DTA, simultaneous PXRD-DSC
      and vapor sorption analysis. In addition, the crystal structures of HH and AH-I
      were determined by single crystal X-ray structure analysis for the first time. HH
      transformed to AH-I, AH-II and AH-III as the temperature was increased from 25
      degrees C to 210 degrees C. At 25 degrees C, AH-I transformed to HH at above
      5%RH. HH and AH-I possessed similar crystal packing patterns and molecular
      structures. 

PMID- 25562842
TI  - N-Acetylcysteine improves mitochondrial function and ameliorates behavioral
      deficits in the R6/1 mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder, involving psychiatric,
      cognitive and motor symptoms, caused by a CAG-repeat expansion encoding an
      extended polyglutamine tract in the huntingtin protein. Oxidative stress and
      excitotoxicity have previously been implicated in the pathogenesis of HD. We
      hypothesized that N-acetylcysteine (NAC) may reduce both excitotoxicity and
      oxidative stress through its actions on glutamate reuptake and antioxidant
      capacity. The R6/1 transgenic mouse model of HD was used to investigate the
      effects of NAC on HD pathology. It was found that chronic NAC administration
      delayed the onset and progression of motor deficits in R6/1 mice, while having an
      antidepressant-like effect on both R6/1 and wild-type mice. A deficit in the
      astrocytic glutamate transporter protein, GLT-1, was found in R6/1 mice. However,
      this deficit was not ameliorated by NAC, implying that the therapeutic effect of
      NAC is not due to rescue of the GLT-1 deficit and associated glutamate-induced
      excitotoxicity. Assessment of mitochondrial function in the striatum and cortex
      revealed that R6/1 mice show reduced mitochondrial respiratory capacity specific
      to the striatum. This deficit was rescued by chronic treatment with NAC. There
      was a selective increase in markers of oxidative damage in mitochondria, which
      was rescued by NAC. In conclusion, NAC is able to delay the onset of motor
      deficits in the R6/1 model of Huntington's disease and it may do so by
      ameliorating mitochondrial dysfunction. Thus, NAC shows promise as a potential
      therapeutic agent in HD. Furthermore, our data suggest that NAC may also have
      broader antidepressant efficacy. 

PMID- 25562847
TI  - Southern Hemisphere control on Australian monsoon variability during the late
      deglaciation and Holocene.
AB  - The evolution of the Australian monsoon in relation to high-latitude temperature
      fluctuations over the last termination remains highly enigmatic. Here we
      integrate high-resolution riverine runoff and dust proxy data from X-ray
      fluorescence scanner measurements in four well-dated sediment cores, forming a NE
      SW transect across the Timor Sea. Our records reveal that the development of the
      Australian monsoon closely followed the deglacial warming history of Antarctica.
      A minimum in riverine runoff documents dry conditions throughout the region
      during the Antarctic Cold Reversal (15-12.9 ka). Massive intensification of the
      monsoon coincided with Southern Hemisphere warming and intensified greenhouse
      forcing over Australia during the atmospheric CO2 rise at 12.9-10 ka. We relate
      the earlier onset of the monsoon in the Timor Strait (13.4 ka) to regional
      changes in landmass exposure during deglacial sea-level rise. A return to dryer
      conditions occurred between 8.1 and 7.3 ka following the early Holocene runoff
      maximum.

PMID- 25562843
TI  - Plant-derived flavanol (-)epicatechin mitigates anxiety in association with
      elevated hippocampal monoamine and BDNF levels, but does not influence pattern
      separation in mice.
AB  - Flavanols found in natural products such as cocoa and green tea elicit structural
      and biochemical changes in the hippocampus, a brain area important for mood and
      cognition. Here, we evaluated the outcome of daily consumption of the flavanol (
      )epicatechin (4 mg per day in water) by adult male C57BL/6 mice on measures of
      anxiety in the elevated plus maze (EPM) and open field (OF). Furthermore, pattern
      separation, the ability to distinguish between closely spaced identical stimuli,
      considered to be mediated by the hippocampal dentate gyrus (DG), was tested using
      the touchscreen. To investigate mechanisms through which (-)epicatechin may exert
      its effects, mice were injected with bromodeoxyuridine (50 mg kg(-1)) to evaluate
      adult hippocampal neurogenesis. In addition, monoaminergic and neurotrophin
      signaling pathway proteins were measured in tissue derived from subject cortices
      and hippocampi. Flavanol consumption reduced anxiety in the OF and EPM. Elevated
      hippocampal and cortical tyrosine hydroxylase, downregulated cortical monoamine
      oxidase-A levels, as well as increased hippocampal brain-derived neurotrophic
      factor (BDNF) and pro-BDNF support the flavanol's anxiolytic effects. In
      addition, elevated pAkt in hippocampus and cortex was observed. (-)Epicatechin
      ingestion did not facilitate touchscreen performance or DG neurogenesis,
      suggesting a non-neurogenic mechanism. The concurrent modulation of complementary
      neurotrophic and monoaminergic signaling pathways may contribute to beneficial
      mood-modulating effects of this flavanol.

PMID- 25562848
TI  - Combating tobacco use in military and veteran populations.

PMID- 25562846
TI  - Randomized controlled trials in environmental health research: unethical or
      underutilized?

PMID- 25562845
TI  - Sensitive and accurate liquid chromatography-tandem mass spectrometry methods for
      quantitative determination of a novel hepatitis C NS5B inhibitor BMS-791325 and
      its active metabolite in human plasma and urine.
AB  - BMS-791325 is a novel hepatitis C NS5B inhibitor which is currently in clinical
      development. To support pharmacokinetic (PK) assessments, sensitive, accurate,
      precise, and reproducible liquid chromatography-tandem mass spectrometry (LC
      MS/MS) methods have been developed and validated for the quantitation of BMS
      791325 and its active N-demethyl metabolite (BMS-794712) in human plasma and
      urine. Plasma and urine samples were extracted with methyl-t-butyl ether followed
      by an LC-MS/MS analysis which was conducted in a multiple reaction monitoring
      (MRM) mode for the simultaneous detection of the two analytes in human plasma
      (0.1-50 ng/mL) and in human urine (5-2500 ng/mL). Intra-run precision (3.0%
      R.S.D.), inter-run precision (5.3% R.S.D.), and accuracy (+/-4.7% deviation) from
      plasma and urine quality control samples provide evidence of the methods accuracy
      and precision. Selectivity, stability in matrices, extraction recovery, matrix
      effect on LC-MS detection, and interference of coadministered drugs (famotidine
      and ritonavir) were all acceptable. Reproducibility of the plasma method was
      demonstrated by reanalysis of a portion of study samples. The results of cross
      validations demonstrated the equivalency of two methods validated in two labs.
      The plasma method was applied to the analysis of several thousand clinical study
      samples for PK evaluations of the drug in normal healthy subjects and in
      patients. The urine method was used in the first in human study to evaluate renal
      clearance and urinary recovery.

PMID- 25562849
TI  - Increasing resilience through promotion of healthy sleep among service members.

PMID- 25562850
TI  - Strengthening malaria prevention and control: integrating West African
      militaries' malaria control efforts. The inaugural meeting of the West African
      Malaria Task Force, April 24-26, 2013, Accra, Ghana.
AB  - From April 24 to 26, 2013, the Armed Forces Health Surveillance Center and the
      U.S. Africa Command cosponsored the inaugural meeting of the West Africa Malaria
      Task Force in Accra, Ghana. The meeting's purpose was to identify common
      challenges, explore regional and transcontinental collaborations, and to share
      knowledge about best practices in the fight against malaria in West Africa.
      Military representatives from Benin, Burkina Faso, Ghana, Liberia, Niger,
      Nigeria, Senegal, and Togo participated in the Task Force; various U.S.
      Government agencies were also represented, including the Department of Defense,
      the Centers for Disease Control and Prevention, and the Agency for International
      Development. African nation participants presented brief overviews of their
      military's malaria prevention and control measures, surveillance programs,
      diagnostic capabilities, and treatment regimens emphasizing gaps within existing
      programs. Representatives from U.S. agencies discussed activities and
      capabilities relevant for the region, challenges and lessons learned regarding
      malaria, and highlighted opportunities for enhanced partnerships to counter
      malaria in West Africa. This article summarizes the major conclusions of the Task
      Force meeting, identifies relevant focus areas for future Task Force activities,
      and outlines opportunities for further inclusion of West African militaries to
      improve regional malaria surveillance and control efforts. 

PMID- 25562851
TI  - Combat internist: the internal medicine experience in a combat hospital in
      Afghanistan.
AB  - Military internists and internal medicine subspecialists are physicians who
      generally work in traditional internal medicine settings. However, when deployed
      to combat settings, they must prepare and adapt their skills for a wide spectrum
      of complex, polytrauma, and multinational patients. There are limitations in
      personnel, equipment, and technical resources that make the circumstances complex
      and demanding. This article highlights some of the unique roles, challenges, and
      experiences of four military internists at the NATO Role 3, a deployed combat
      hospital in Afghanistan. 

PMID- 25562852
TI  - Gonorrhea surveillance in Ghana, Africa.
AB  - OBJECTIVES: We face the specter of global transmission of highly resistant
      Neisseria gonorrhoeae. The U.S. Department of Defense's Armed Forces Health
      Surveillance Center has engaged many military and civilian partners (including
      Ghana) in a sexually transmitted infections (STI) program to address emerging
      needs in STI surveillance. We implemented gonorrhea surveillance in Ghana to fill
      the gap in knowledge regarding gonorrhea prevalence and antimicrobial resistance
      characterization in Ghana. METHODS: Gonorrhea surveillance was conducted from
      June 2012 to March 2013 as one of the AFHSC surveillance network partners at two
      Ghana Armed Forces (GAF) military clinics. The population encompassed a
      convenience sampling of patients presenting with STI symptoms. Urine was taken
      for nucleic acid amplification testing (NAAT). A urethral or cervical/vaginal
      specimen was obtained for culture and antibiotic susceptibility testing. RESULTS:
      13/220 (6%) specimens tested were positive by culture (7 of which were
      confirmed); and 39/213 (18%) specimens tested were positive by NAAT. Positive
      results were biased toward men. Cultures were resistant to ciprofloxacin,
      penicillin and tetracycline and sensitive to cephalosporins. CONCLUSION: This
      investigation provides data on gonorrhea prevalence and resistance profiles in
      Ghana hitherto poorly characterized. We note significant resistance to
      fluoroquinolones without the presence of resistance yet to the cephalosporins.

PMID- 25562853
TI  - Exploring the impact of a pedometer on body composition and physical fitness in a
      cohort of U.S. military medical students: a pilot study.
AB  - Military medical professionals play a central role in preventing and treating
      obesity among America's warriors through training, medical care, and their
      personal example. Unfortunately, medical students in both undergraduate and
      graduate settings often experience declines in physical fitness. Pedometry has
      been demonstrated as one means of promoting fitness with 10,000 steps/day
      generally accepted as a key benchmark. With this in mind, we used pedometry as an
      incentive during the preclinical years to encourage students to adopt a more
      active lifestyle. Findings suggest that participants that consistently report
      meeting the 10,000 steps/day maintained or improved their aerobic fitness. 

PMID- 25562854
TI  - Sun exposure knowledge and practices survey of maintenance squadrons at Travis
      AFB.
AB  - Recent literature has shown that the incidence of melanoma skin cancer is
      significantly higher in the U.S. military than for civilians and is higher in the
      U.S. Air Force than other military branches. No studies have investigated
      military specific exposures that might increase this risk. Using a cross
      sectional survey we evaluated sun exposure knowledge and practices of U.S. Air
      Force flight line workers whose duties may lead to increased melanoma risk. The
      specific aims of this study were to (1) describe the social demographic
      characteristics of maintenance personnel, (2) describe current sun blocking
      practices in maintenance personnel, (3) describe knowledge about sun exposure
      risks and benefits, and (4) identify factors influencing practices that increase
      the risk for developing melanoma. Our survey of 356 Air Force flight line
      personnel showed that 67% of their career required working in direct sunlight,
      94.7% of personnel know that it is recommended to use sun blocking methods, yet
      the majority do not regularly use sun protective measures. Our results suggest
      that the increased incidence of melanoma in the U.S. Air Force may be due to the
      type or duration of ultraviolet exposure. 

PMID- 25562855
TI  - A review of skin conditions in modern warfare and peacekeeping operations.
AB  - Skin is the most exposed organ of the body, and military personnel face many
      external skin threats. As a result, skin disease is an important source of
      morbidity among military personnel deployed on combat or peacekeeping operations.
      This article reviews the most common conditions seen by deployed military
      dermatologists. A PubMed search was used to identify articles in English, written
      between 1965 and 2014, using medical subject headings "military medicine" AND
      "skin disease" or "military personnel" AND "skin disease." The five most common
      reasons for physician consultation for skin conditions in wartime since the
      Vietnam War were warts (10.7%), fungal infections (10.4%), acne (9.0%),
      nonspecific eczematous conditions (7.1%), and sexually transmitted diseases
      (6.1%). There was a significant difference in the skin conditions seen in the hot
      and humid climates of Vietnam and East Timor, where bacterial and fungal
      infections were more common reasons for consultation, and the dry climates of
      Bosnia and Iraq, where eczematous conditions made up a larger part of the
      dermatologic caseload. 

PMID- 25562856
TI  - Tuberculosis contact investigation in a military health care setting: case report
      and evidence review.
AB  - Tuberculosis (TB) remains a global threat to the U.S. armed forces. A single
      individual with TB disease exerts an immediate and disruptive impact upon
      patients' lives, military operations, and daily functioning at military treatment
      facilities. Medical personnel in operational or limited-resource settings are
      sometimes challenged to perform a TB outbreak investigation with minimal
      specialized training or limited logistic assistance. This article presents a case
      of a patient with TB disease presenting to a large military treatment facility
      and outlines the current, evidence-based recommendations for performing a TB
      outbreak investigation. 

PMID- 25562857
TI  - Examining the influence of mild traumatic brain injury and posttraumatic stress
      disorder on alcohol use disorder in OEF/OIF veterans.
AB  - OBJECTIVES: Examine (1) impact of mild traumatic brain injury (mTBI) on
      posttraumatic stress disorder (PTSD) symptoms, (2) frequency of alcohol use
      disorder in male and female combat Veterans, and (3) influence of PTSD and mTBI
      on alcohol use disorder. METHOD: A retrospective medical-record review extracted
      the following data for Operation Enduring Freedom/Operation Iraqi Freedom
      Veterans (N = 1,278) who completed a semi-structured mental health evaluation:
      alcohol use disorder diagnoses, PTSD symptom criteria, and Brief Traumatic Brain
      Injury Screen. Logistic regressions tested if PTSD and mTBI predicted which
      Veterans had an alcohol use disorder diagnosis. RESULTS: Veterans with mTBI had
      more re-experiencing, avoidance, and hyperarousal symptoms than Veterans without
      mTBI. Men and women differed regarding alcohol use. For men, PTSD predicted
      alcohol use diagnosis while mTBI did not. For women, neither mTBI nor PTSD
      predicted alcohol use diagnosis. CONCLUSION: Findings from this study can inform
      treatment providers by alerting them to the possibility of subthreshold PTSD in
      Veterans with mTBI. Providers may begin PTSD treatments or consider targeting
      hyperarousal symptoms early in treatment to reduce distress. PTSD is also
      uniquely associated with alcohol use disorder in male Veterans, while more
      research on predictors of alcohol use disorder is needed for female Veterans.

PMID- 25562858
TI  - Factors associated with psychiatric evacuation among service members deployed to
      Operation Enduring Freedom and Operation Iraqi Freedom, January 2004 to September
      2010.
AB  - OBJECTIVES: To calculate the annual rate of psychiatric evacuation of U.S.
      Service members out of Iraq and Afghanistan and identify risk factors for
      evacuation. METHODS: Descriptive and regression analyses were performed using
      deployment records for Service members evacuated from January 2004 through
      September 2010 with a psychiatric diagnosis, and a 20% random sample of all other
      deployers (N = 364,047). RESULTS: A total of 5,887 deployers psychiatrically
      evacuated, 3,951 (67%) of which evacuated on first deployment. The rate increased
      from 72.9 per 100,000 in 2004 to 196.9 per 100,000 in 2010. Evacuees were
      overrepresented in both combat and supporting duty assignments. In multivariate
      analysis, Army active duty had the highest odds of evacuation relative to Army
      National Guard (adjusted odds ratio [AOR] 0.852, 95% confidence interval [CI]
      0.790-0.919), Army Reserve (AOR 0.825, 95% CI 0.740-0.919), and all other
      components. Accessions in 2005 had the highest risk (AOR 1.923, 95% CI 1.621
      2.006) relative to pre-2001 accessions. CONCLUSIONS: Risk for psychiatric
      evacuation is highest among the Army Active Component. A strong link between
      multiple deployments or combat-related exposure and psychiatric evacuation is not
      apparent. Increased risk among post-2001 accessions suggests further review of
      changes in recruitment, training, and deployment policies and practices.

PMID- 25562859
TI  - Risk and protective factors for suicidal ideation and suicide attempts among
      deployed Danish soldiers from 1990 to 2009.
AB  - OBJECTIVE: The study was undertaken to identify risk and protective factors for
      suicidal ideation and suicide attempts among deployed Danish soldiers. Research
      on suicide among Danish veterans has only been conducted to a limited degree.
      METHOD: The method applied was a questionnaire survey administered to a
      population of 1,264 Danish soldiers deployed from 1990 to 2009. The data were
      analyzed using backward logistic regression modeling in SAS 9.2. RESULTS: In the
      logistic regression analysis, the following were significant risk factors for
      suicidal ideation: drug abuse, a poor financial situation before deployment, a
      heavy workload and/or repatriation during deployment, and attending a poor
      athletic and recreation program after deployment. Significant protective factors
      against suicidal ideation were support from friends at home during deployment and
      appreciation by the general population after deployment. Significant risk factors
      for suicide attempts were an unhappy childhood and pointless tasks during
      deployment. No significant protective factors against suicide attempts were
      identified. CONCLUSION: On the basis of the results presented in this study,
      intervention against suicidal behavior would benefit from screening for certain
      childhood issues, drug abuse, and poor financial situation before deployment.
      During deployment, measures should be taken to minimize the amount of meaningless
      tasks and heavy workloads. At the same time, efficient ways of communicating with
      home should be ensured. After deployment, good athletic and recreation programs
      should be warranted for all military personnel-including repatriated soldiers.
      Finally, priority should be given to ensure public appreciation of what deployed
      soldiers accomplish.

PMID- 25562860
TI  - Daily insufficient sleep and active duty status.
AB  - OBJECTIVE: We assessed the relationship between active duty status and daily
      insufficient sleep in a telephone survey. METHODS: U.S. military service status
      (recent defined as past 12 months and past defined as >12 months ago) and daily
      insufficient sleep in the past 30 days were assessed among 566,861 adults aged 18
      to 64 years and 271,202 adults aged >= 65 years in the 2009 to 2010 Behavioral
      Risk Factor Surveillance System surveys. RESULTS: Among ages 18 to 64 years, 1.1%
      reported recent active duty and 7.1% had past service; among ages >= 65 years,
      0.6% reported recent and 24.6% had past service. Among ages 18 to 64 years,
      prevalence of daily insufficient sleep was 13.7% among those reporting recent
      duty, 12.6% for those with past service, and 11.2% for those with no service.
      Insufficient sleep did not vary significantly with active duty status among ages
      >= 65 years. After adjustment for sociodemographic characteristics, health
      behaviors, and frequent mental distress in multivariate logistic regression
      models, respondents aged 18 to 64 years with recent active duty were 34% more
      likely and those with past service were 23% more likely to report daily
      insufficient sleep than those with no service (p < 0.05, both). CONCLUSIONS:
      Adults with either recent or past active duty have a greater risk for daily
      insufficient sleep.

PMID- 25562861
TI  - MOE vs. M&E: considering the difference between measuring strategic effectiveness
      and monitoring tactical evaluation.
AB  - Measuring the effectiveness of military Global Health Engagements (GHEs) has
      become an area of increasing interest to the military medical field. As a result,
      there have been efforts to more logically and rigorously evaluate GHE projects
      and programs; many of these have been based on the Logic and Results Frameworks.
      However, while these Frameworks are apt and appropriate planning tools, they are
      not ideally suited to measuring programs' effectiveness. This article introduces
      military medicine professionals to the Measures of Effectiveness for Defense
      Engagement and Learning (MODEL) program, which implements a new method of
      assessment, one that seeks to rigorously use Measures of Effectiveness (vs.
      Measures of Performance) to gauge programs' and projects' success and fidelity to
      Theater Campaign goals. While the MODEL method draws on the Logic and Results
      Frameworks where appropriate, it goes beyond their planning focus by using the
      latest social scientific and econometric evaluation methodologies to link on-the
      ground GHE "lines of effort" to the realization of national and strategic goals
      and end-states. It is hoped these methods will find use beyond the MODEL project
      itself, and will catalyze a new body of rigorous, empirically based work, which
      measures the effectiveness of a broad spectrum of GHE and security cooperation
      activities. We based our strategies on the principle that it is much more cost
      effective to prevent conflicts than it is to stop one once it's started. I cannot
      overstate the importance of our theater security cooperation programs as the
      centerpiece to securing our Homeland from the irregular and catastrophic threats
      of the 21st Century.-GEN James L. Jones, USMC (Ret.). 

PMID- 25562862
TI  - Metabolic syndrome in the Military Health System based on electronic health data,
      2009-2012.
AB  - Metabolic syndrome prevalence in the United States rose from 27% to 34.2% between
      1999-2000 and 1999-2006. However, prevalence has not been determined in the
      Military Health System. This retrospective descriptive study included enrolled
      Military Health System adults during fiscal years 2009-2012. We explored three
      populations (nonactive duty, active duty, and Air Force active duty) and their
      metabolic syndrome components (body mass index or waist circumference, blood
      glucose test, triglyceride, high density lipoprotein, and blood pressure). The
      active duty sample (who had all five components measured) was representative of
      its population, but the nonactive duty sample was not. Therefore, we reported
      component-wise prevalence for both nonactive and active duty populations, but
      only reported prevalence of metabolic syndrome for active duty. A decreasing
      trend, greater in men, was seen. Crude prevalence in 2012 was higher among men
      and highest among males and females aged 45-64. Only Air Force active duty data
      contained waist circumference measurements, enabling comparison to the United
      States. This subgroup prevalence was significantly lower than the United States
      prevalence in 2010 for both genders in every age group. Although decreasing
      metabolic syndrome prevalence is promising, prevalence is still high and future
      research should explore policies to help lower the prevalence. 

PMID- 25562863
TI  - History of the U.S. Navy Body Composition program.
AB  - The Navy currently employs maximum weight-for-height tables and body fat
      prediction equations based on circumference measurements to assess body
      composition. However, many Sailors believe the current method fails to accurately
      predict body fat percentage. As a result, the Naval Health Research Center (NHRC)
      conducted numerous studies in an attempt to improve the accuracy and reliability
      of the Navy's Body Composition Analysis program. In 2012, NHRC conducted a study
      that researched the feasibility of using a single abdominal circumference (AC)
      measurement in lieu of circumference measurements. The Air Force and National
      Institutes of Health (NIH) employ a single AC measurement taken at the superior
      border of the iliac crest to assess body composition and all-cause mortality
      risk. Although the Air Force and NIH use the iliac crest, NHRC is proposing the
      Navy use the umbilicus as the AC site since it is less invasive and easier to
      identify. If implemented, the Navy would use cutoff values of 40 in. and 36 in.
      for males and females, respectively. The purpose of this article is to provide a
      brief history of the Navy's Body Composition Analysis program as well as propose
      the transition from circumference measurements to a single AC measurement. 

PMID- 25562864
TI  - Pathogens present in acute mangled extremities from Afghanistan and subsequent
      pathogen recovery.
AB  - Given the changing epidemiology of infecting pathogens in combat casualties, we
      evaluated bacteria and fungi in acute traumatic wounds from Afghanistan. From
      January 2013 to February 2014, 14 mangled lower extremities from 10 explosive
      device injured casualties were swabbed for culture at Role 3 facilities. Bacteria
      were recovered from all patients on the date of injury. Pathogens recovered
      during routine patient care were recorded. The median injury severity score was
      29, median initial Role 3/4 blood product support was 32 units, and median
      evacuation time was 42 minutes to first surgical care. Gram-positive bacteria
      were found in some wounds but not methicillin-resistant Staphylococcus aureus or
      vancomycin-resistant Enterococcus. Most wounds were colonized with low-virulence,
      environmental gram-negative bacteria, and not recovered again during therapy,
      reflecting wound contamination. Only one wound had the same bacteria (E. cloacae)
      throughout care at the Role 3, 4, and 5 facilities. Three cultures from two
      patients had multidrug-resistant bacteria (E. cloacae, E. coli), all detected at
      Role 5 facilities. Molds were not detected at Role 3, whereas one patient had a
      mold at Role 4 and 5. Mangled lower extremity injuries have a high contamination
      rate with environmental organisms, which are not typically associated with
      infections during the course of the patient's care. 

PMID- 25562866
TI  - Responding to traveling patients' seasonal demand for health care services.
AB  - The Veterans Health Administration (VHA) provides care to over 8 million Veterans
      and operates over 1,700 sites of care across 21 regional networks in the United
      States. Health care providers within VHA report large seasonal variation in the
      demand for services, especially in the southern United States because of arrival
      of "snowbirds" during the winter. Because resource allocation activities are
      primarily carried out through an annual budgeting process, the seasonal load
      imposed by "traveling Veterans"-Veterans that seek care at VHA sites outside of
      their home network-make providing high-quality services more challenging. This
      work constitutes the first major effort within VHA to understand the impact of
      traveling Veterans. We discovered strong seasonal fluctuations in demand at a
      clinic located in the southeastern United States and developed a seasonal
      autoregressive integrated moving average model to help the clinic forecast demand
      for its services with significantly less error than historical averaging. Monte
      Carlo simulation of the clinic revealed that physicians are overutilized,
      suggesting the need to re-evaluate how the clinic is currently staffed. More
      broadly, this study demonstrates how operations management methods can assist
      operational decision making at other clinics and medical centers both within and
      outside VHA. 

PMID- 25562867
TI  - U.S. Army Hospital Ship "Relief".

PMID- 25562865
TI  - Healthcare-associated pneumonia among U.S. combat casualties, 2009 to 2010.
AB  - Although there is literature evaluating infectious complications associated with
      combat-related injuries from Iraq and Afghanistan, none have evaluated pneumonia
      specifically. Therefore, we assessed a series of pneumonia cases among wounded
      military personnel admitted to Landstuhl Regional Medical Center, and then
      evacuated further to participating U.S. military hospitals. Of the 423 casualties
      evacuated to the United States, 36 developed pneumonia (8.5%) and 30 of these
      (83.3%) were ventilator-associated. Restricting to 162 subjects admitted to
      intensive care, 30 patients had pneumonia (18.5%). The median Injury Severity
      Score was higher among subjects with pneumonia (23.0 vs. 6.0; p < 0.01). There
      were 61 first-isolate respiratory specimens recovered from 31 pneumonia subjects,
      of which 56.1% were gram-negative, 18.2% were gram-positive, and 18.2% were
      fungal. Staphylococcus aureus and Pseudomonas aeruginosa were most commonly
      recovered (10.6%, and 9.1%, respectively). Thirteen bacterial isolates (26.5%)
      were multidrug-resistant. Outcome data were available for 32 patients, of which
      26 resolved their infection without progression, 5 resolved after initial
      progression, and 1 died. Overall, combat-injured casualties suffer a relatively
      high rate of pneumonia, particularly those requiring mechanical ventilation.
      Although gram-negative pathogens were common, S. aureus was most frequently
      isolated. Continued focus on pneumonia prevention strategies is necessary for
      improving combat care. 

PMID- 25562868
TI  - A case of post-traumatic stress disorder presenting with anorexia nervosa
      restrictive type.
AB  - We present a case of combat-related post-traumatic stress disorder that made and
      unusual initial clinical presentation with anorexia nervosa restrictive type. 

PMID- 25562869
TI  - Significant reduction in phantom limb pain after low-frequency repetitive
      transcranial magnetic stimulation to the primary sensory cortex.
AB  - OBJECTIVE: Phantom limb pain (PLP) is believed to be linked to the reorganization
      of the deafferented sensory cortex. We present a case of a patient with upper
      extremity PLP who was successfully treated with repetitive transcranial magnetic
      stimulation (rTMS). METHODS: We treated an active duty service member who
      suffered an amputation of his right upper extremity after sustaining a blast
      injury in Afghanistan. He had 28 sessions of alternating sequences of rTMS to the
      left dorsolateral prefrontal cortex and primary sensory cortex of the left
      cerebral hemisphere. Pain intensity was assessed with the Visual Analogue Scale.
      RESULTS: We delivered 1 Hz stimulation to the sensory cortex corresponding to the
      area of amputation five times a week. After 4 sessions, the patient's pain
      decreased from a Visual Analogue Scale of 5 to 2. Left 10 Hz stimulation was
      added and after 28 sessions, the pain decreased from 2 to 1. CONCLUSIONS: Our
      findings support that rTMS was an effective modality for this patient in treating
      his PLP. The significance of 10 Hz stimulation is unknown because of the lack of
      an effect size and is possibly associated with a floor effect.

PMID- 25562870
TI  - Symptomatic lumbar osteochondroma treated via a multidisciplinary military
      surgical team: case report and review of the literature.
AB  - The authors describe the case of a giant osteochondroma emanating from the L5
      vertebral body and extending into the retroperitoneum of a 40-year-old man,
      causing low back pain. Osteochondromas are benign bony tumors that typically
      occur within the appendicular skeleton, although in the sporadic form, up to 4%
      occur in the spine. A review of the English language literature has returned 44
      cases of lumbar osteochondroma, including the present example. The lesions were
      sporadic in 81% of cases. Mean age of presentation overall is 39.5 years, with a
      mean age of 18.4 years (range 8-34 years) for hereditary cases and 45.7 years
      (range 11-81 years) for solitary lesions. Of the instances where gender was
      reported, 64% were male. The most common level of origin was L4 (38%). The most
      common anatomic site of origin was the inferior articular process (one-third). Of
      those lesions treated operatively, 46% underwent simple decompression, with 22%
      requiring decompression and fusion. This particular lesion was resected via a
      transperitoneal approach performed by a multidisciplinary team of neurosurgeons,
      vascular surgeons, and urologists. The bony tumor measured 6.1 * 7.8 * 7.7 cm.
      Removal of the lesion resulted in a significant improvement of the patient's
      symptoms. 

PMID- 25562871
TI  - Concurrent bilateral femoral neck stress fractures in a military recruit: a case
      report.
AB  - BACKGROUND: Stress fractures are overuse injuries that historically afflict a
      large number of military recruits, likely because of the sudden increase of high
      intensity activity, such as running and marching. CASE: A 23-year-old male U.S.
      Air Force recruit presented with hip pain during his second week of basic
      training and was diagnosed with bilateral femoral neck stress fractures, grade 4
      on the right and grade 3 on the left. This is the first known case of concurrent
      bilateral femoral neck stress fractures in a U.S. military recruit reported in
      the medical literature. CONCLUSION: This report describes a severe case of stress
      fracture in an individual with no readily identifiable risk factors.

PMID- 25562872
TI  - Successful nonoperative management of coracoid fracture associated with suture
      button fixation of acromioclavicular separation.
AB  - A young active duty soldier underwent acromioclavicular reconstruction with
      hamstring autograft after sustaining a shoulder separation. At 3 months
      postoperatively, the patient fell and sustained a fracture of the coracoid
      process. The patient elected for nonoperative management of the coracoid
      fracture. Despite eventual nonunion of the fracture, the patient had excellent
      functional outcomes and returned to military duty without limitation. Although
      some authors advocate operative fixation, especially in a young and active
      cohort, excellent outcomes can be obtained with nonoperative management.

PMID- 25562873
TI  - Orthobiological augmentation of consecutive rotator cuff repair failure and
      deltoid dehiscence.
AB  - We present a case of postsurgical deltoid insufficiency occurring after augmented
      revision of a failed prior rotator cuff repair. Revision deltoid repair with
      deltoid imbrication and orthobiological augmentation was dually performed,
      resulting in successful deltoid and rotator cuff healing and improved clinical
      outcomes. 

PMID- 25562874
TI  - Blood cell exchange in the treatment of exercise-induced rhabdomyolysis in a
      patient with sickle cell trait.
AB  - We report the use of red blood cell exchange (RBCex) to treat rhabdomyolysis
      complicated by acute kidney injury in a 16-year-old African-American female with
      sickle cell trait (SCT). Treatment with aggressive fluid and electrolyte
      management failed to stem the rise in her creatine kinase, and RBCex was
      instituted 27 hours after symptom onset. She had a transient improvement in her
      creatine kinase following this treatment although it failed to resolve a
      developing lower extremity compartment syndrome, requiring bilateral lower
      extremity fasciotomies. The mechanism of exercise-induced rhabdomyolysis in
      individuals with SCT is theorized to result from localized hypoxia and acidosis
      within exercising muscle significant enough to cause a localized sickling crisis
      with resultant rhabdomyolysis. Despite the unique pathophysiology of
      rhabdomyolysis in individuals with SCT, there is a paucity of adjunctive
      treatment options beyond fluid and electrolyte therapy. To the best of our
      knowledge, RBCex for treatment of rhabdomyolysis in a patient with SCT has been
      described only once before by Huang et al. We report here a second case in the
      use of RBCex in the treatment of rhadbomyolysis in a patient with SCT. 

PMID- 25562875
TI  - Cervicothoracic intradural spinal lipoma without dyraphism diagnosed postpartum.
AB  - BACKGROUND: Intradural spinal lipoma without evidence of dysraphism is a rare
      occurrence comprising approximately 1% of all spinal tumors. CASE: An 18-year-old
      female who, following her primary cesarean section, began developing
      progressively worsening lower extremity weakness, paresthesias, spasticity, and
      hyperreflexia. Magnetic resonance imaging diagnosed a cervicothoracic intradural
      spinal lipoma. She underwent an osteoplastic laminotomy with subtotal resection
      of intradural lipoma with an excellent prognosis. CONCLUSION: This case
      highlights the need for broad differential diagnoses if symptoms do not correlate
      with the typical postpartum recovery. Our patient's case is the first to describe
      symptoms developing postpartum with excellent prognosis because of rapid
      evaluation and diagnosis.

PMID- 25562876
TI  - Cutaneous reactions associated with ACAM2000 smallpox vaccination in a deploying
      U.S. Army unit.
AB  - Since 2003, the U.S. Army has vaccinated deploying troops for smallpox. In 2008,
      the U.S. military transitioned to the second-generation vaccine ACAM2000.
      Cutaneous adverse events associated with this vaccine are rarely characterized.
      We review the medical literature on cutaneous adverse events with ACAM2000 and
      describe four new cases that occurred in primary vaccinees at Fort Wainwright,
      Alaska. Four cases of disseminated papulovesicular lesions occurred out of 500
      smallpox vaccinations given at Fort Wainwright, Alaska. Each case was followed by
      dermatology and preventive medicine. Biopsy specimens were examined at Walter
      Reed Army Medical Center and the U.S. Centers for Disease Control and Prevention.
      Three of the cases had variable clinical history of dermatitis. Case 1
      experienced the most extensive lesions and case duration, and Case 4 the least.
      All biopsy sample results confirmed immune-mediated hypersensitivity. This study
      relied on self-reporting and on surveillance by unit medical staff to identify
      cases. Each case also received multiple other concurrent vaccinations. Further
      study is needed to increase our knowledge of these cutaneous reactions and
      demonstrate possible associated or causal factors. 

PMID- 25562877
TI  - Dysfluency in a service member with comorbid diagnoses: a case study.
AB  - PURPOSE: Because of the noted increase in dysfluency among service members
      returning from Iraq and Afghanistan, this article describes differentiation
      between the various types of fluency as well as an evaluation and treatment
      course of a service member returning from war with the comorbid diagnoses of post
      traumatic stress disorder, mild traumatic brain injury, and resulting stuttering.
      METHOD: The subject of this case study signed a consent on his admission to
      National Intrepid Center of Excellence (NICoE) for use of any clinical
      information for research purposes. The patient-centered method of his evaluation
      and treatment is one standard for NICoE's 4-week treatment program. Fluency data
      were collected from the patient using observational and standardized assessment
      (Stuttering Severity Instrument-4). The patient underwent a course of treatment
      using fluency strategy education and practice to lead to generalization of skills
      across all communication environments. CONCLUSION: This service member responded
      favorably following a short course of fluency treatment because of the
      psychogenic nature of his stuttering, which was a symptom of his psychological
      health diagnoses. The NICoE patient-centered care model achieved the desired
      results of fluency and improved overall function in this service member.

PMID- 25562878
TI  - Suspected hypercalcemia induced ST-segment elevation in a patient with
      sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disease that affects 10 to 20 people
      per 100,000 in the United States. Hypercalcemia is a known side effect of the
      disease and in rare instances has been shown to cause ST-segment elevation on
      electrocardiogram testing that mimics myocardial infarction. Herein, we present a
      rare case of a 55-year-old, asymptomatic African-American male with sarcoidosis
      and hydrochlorothiazide usage presenting with ST-segment elevation of the
      anterior leads secondary to hypercalcemia. Urgent cardiac catheterization showed
      normal coronary arteries without blockage. The patient's hypercalcemia was
      corrected with intravenous fluids and the ST-segment elevation resolved. The
      exact mechanism of ST-segment elevation induced hypercalcemia is unknown.
      Treatment of the underlying cause of the hypercalcemia is the mainstay of
      therapy. 

PMID- 25562879
TI  - Acute, proximal aortic dissection with negative D-Dimer assay and normal portable
      chest radiograph: a case report.
AB  - Acute aortic dissection is one of the most devastating and time-sensitive
      diagnosis to consider in young adults with chest pain. Military medicine is
      represented by a larger proportion of 18- to 50-year-old individuals than is seen
      in the general medical population. Although uncommon in frequency, younger
      patients are more likely to suffer from proximal, aortic dissections. Chest
      radiographs and D-Dimer assays are used frequently as risk stratification tools,
      but have significant limitations in these more proximal dissections. Because of
      the frequency and lethality of nonspecific presentations, there exists a need for
      a sensitive screening tool. This case report presents a 43-year-old male with a
      concerning history and physical examination for aortic dissection, but a normal
      portable chest radiograph and a normal D-Dimer assay. It highlights the
      importance of clinical acumen in developing and maintaining a high clinical index
      of suspicion based on a Bayesian pretest probability model. 

PMID- 25562880
TI  - Cerebellar ischemia manifesting as vertical diplopia: a case study on skew
      deviation.
AB  - PURPOSE: Skew deviation mimics superior oblique palsy. Associated findings can
      include ocular torsion, head tilt, headache, and neurologic symptoms that may
      help localize the responsible intracranial lesion. Accurate diagnosis is
      essential in determining and treating the underlying cause. Imaging options will
      be reviewed. CASE REPORT: A 29-year-old white male presented to the emergency
      room with sudden onset vertical diplopia after self-neck manipulation. An
      ophthalmic evaluation led to the diagnosis of skew deviation. Diagnostic imaging
      revealed an infarct of the cerebellum likely secondary to a vertebral artery
      dissection. Besides neck manipulation, other possible contributing factors
      include smoking, elevated cholesterol, and elevated testosterone. Symptoms
      resolved within 24 hours and the patient was treated with aspirin and
      atorvastatin calcium. CONCLUSIONS: Skew deviation must be a consideration in
      patients with vertical diplopia, and ruled out before a superior oblique palsy
      diagnosis. Vertebral artery dissections are uncommon in the general population
      but can account for up to 25% of ischemic strokes in the young and middle-aged.
      Smoking, high cholesterol, and high testosterone are known risk factors of
      stroke. Research is inconclusive on spinal manipulation's relation to stroke.
      This report presents an example of neck manipulation directly preceding skew
      deviation secondary to stroke.

PMID- 25562881
TI  - Sporadic Creutzfeldt-Jakob disease in a Navy Commander: case report and review of
      the literature.
AB  - Sporadic Creutzfeldt-Jakob disease is a rare disorder that typically presents as
      rapidly progressive dementia. We present a case of a highly functioning 41-year
      old Navy Commander with sporadic Creutzfeldt-Jakob disease, to include the
      diagnostic challenges, rapid clinical deterioration, and limited treatment
      options. 

PMID- 25562882
TI  - Uterine arteriovenous malformation, images, and management.
AB  - BACKGROUND: Uterine arteriovenous malformation (AVM) is an infrequently described
      cause of severe genital tract bleeding. This is an important diagnostic
      consideration as therapeutic options differ significantly from those utilized
      with alternate etiologies of genital tract bleeding. CASE: A 30-year-old
      multiparous female presented initially with vaginal bleeding, and subsequently
      with intra-abdominal hemorrhage. She was diagnosed with uterine AVM, and was
      managed with uterine artery embolization followed by eventual hysterectomy.
      CONCLUSION: AVMs, both congenital and acquired, are diagnosed utilizing a range
      of radiographic tools. Management modalities include embolization and
      hysterectomy. Our patient presented uniquely with intra-abdominal hemorrhage.
      Previously managed with uterine artery embolization, hysterectomy became
      necessary because of her clinical presentation.

PMID- 25562884
TI  - The pleasure of publishing.
AB  - When assessing manuscripts eLife editors look for a combination of rigour and
      insight, along with results and ideas that make other researchers think
      differently about their subject. 

PMID- 25562883
TI  - Nup98 FG domains from diverse species spontaneously phase-separate into particles
      with nuclear pore-like permselectivity.
AB  - Nuclear pore complexes (NPCs) conduct massive transport mediated by shuttling
      nuclear transport receptors (NTRs), while keeping nuclear and cytoplasmic
      contents separated. The NPC barrier in Xenopus relies primarily on the
      intrinsically disordered FG domain of Nup98. We now observed that Nup98 FG
      domains of mammals, lancelets, insects, nematodes, fungi, plants, amoebas,
      ciliates, and excavates spontaneously and rapidly phase-separate from dilute
      (submicromolar) aqueous solutions into characteristic 'FG particles'. This
      required neither sophisticated experimental conditions nor auxiliary eukaryotic
      factors. Instead, it occurred already during FG domain expression in bacteria.
      All Nup98 FG phases rejected inert macromolecules and yet allowed far larger NTR
      cargo complexes to rapidly enter. They even recapitulated the observations that
      large cargo-domains counteract NPC passage of NTR?cargo complexes, while cargo
      shielding and increased NTR?cargo surface-ratios override this inhibition. Their
      exquisite NPC-typical sorting selectivity and strong intrinsic assembly
      propensity suggest that Nup98 FG phases can form in authentic NPCs and indeed
      account for the permeability properties of the pore. 

PMID- 25562885
TI  - Normalisation of brain connectivity through compensatory behaviour, despite
      congenital hand absence.
AB  - Previously we showed, using task-evoked fMRI, that compensatory intact hand usage
      after amputation facilitates remapping of limb representations in the cortical
      territory of the missing hand (Makin et al., 2013a). Here we show that
      compensatory arm usage in individuals born without a hand (one-handers) reflects
      functional connectivity of spontaneous brain activity in the cortical hand
      region. Compared with two-handed controls, one-handers showed reduced symmetry of
      hand region inter-hemispheric resting-state functional connectivity and
      corticospinal white matter microstructure. Nevertheless, those one-handers who
      more frequently use their residual (handless) arm for typically bimanual daily
      tasks also showed more symmetrical functional connectivity of the hand region,
      demonstrating that adaptive behaviour drives long-range brain organisation. We
      therefore suggest that compensatory arm usage maintains symmetrical sensorimotor
      functional connectivity in one-handers. Since variability in spontaneous
      functional connectivity in our study reflects ecological behaviour, we propose
      that inter-hemispheric symmetry, typically observed in resting sensorimotor
      networks, depends on coordinated motor behaviour in daily life. 

PMID- 25562886
TI  - The surveillance error grid.
AB  - Currently used error grids for assessing clinical accuracy of blood glucose
      monitors are based on out-of-date medical practices. Error grids have not been
      widely embraced by regulatory agencies for clearance of monitors, but this type
      of tool could be useful for surveillance of the performance of cleared products.
      Diabetes Technology Society together with representatives from the Food and Drug
      Administration, the American Diabetes Association, the Endocrine Society, and the
      Association for the Advancement of Medical Instrumentation, and representatives
      of academia, industry, and government, have developed a new error grid, called
      the surveillance error grid (SEG) as a tool to assess the degree of clinical risk
      from inaccurate blood glucose (BG) monitors. A total of 206 diabetes clinicians
      were surveyed about the clinical risk of errors of measured BG levels by a
      monitor. The impact of such errors on 4 patient scenarios was surveyed. Each
      monitor/reference data pair was scored and color-coded on a graph per its average
      risk rating. Using modeled data representative of the accuracy of contemporary
      meters, the relationships between clinical risk and monitor error were calculated
      for the Clarke error grid (CEG), Parkes error grid (PEG), and SEG. SEG action
      boundaries were consistent across scenarios, regardless of whether the patient
      was type 1 or type 2 or using insulin or not. No significant differences were
      noted between responses of adult/pediatric or 4 types of clinicians. Although
      small specific differences in risk boundaries between US and non-US clinicians
      were noted, the panel felt they did not justify separate grids for these 2 types
      of clinicians. The data points of the SEG were classified in 15 zones according
      to their assigned level of risk, which allowed for comparisons with the classic
      CEG and PEG. Modeled glucose monitor data with realistic self-monitoring of blood
      glucose errors derived from meter testing experiments plotted on the SEG when
      compared to the data plotted on the CEG and PEG produced risk estimates that were
      more granular and reflective of a continuously increasing risk scale. The SEG is
      a modern metric for clinical risk assessments of BG monitor errors that assigns a
      unique risk score to each monitor data point when compared to a reference value.
      The SEG allows the clinical accuracy of a BG monitor to be portrayed in many
      ways, including as the percentages of data points falling into custom-defined
      risk zones. For modeled data the SEG, compared with the CEG and PEG, allows
      greater precision for quantifying risk, especially when the risks are low. This
      tool will be useful to allow regulators and manufacturers to monitor and evaluate
      glucose monitor performance in their surveillance programs. 

PMID- 25562887
TI  - Computing the surveillance error grid analysis: procedure and examples.
AB  - The surveillance error grid (SEG) analysis is a tool for analysis and
      visualization of blood glucose monitoring (BGM) errors, based on the opinions of
      206 diabetes clinicians who rated 4 distinct treatment scenarios. Resulting from
      this large-scale inquiry is a matrix of 337 561 risk ratings, 1 for each pair of
      (reference, BGM) readings ranging from 20 to 580 mg/dl. The computation of the
      SEG is therefore complex and in need of automation. The SEG software introduced
      in this article automates the task of assigning a degree of risk to each data
      point for a set of measured and reference blood glucose values so that the data
      can be distributed into 8 risk zones. The software's 2 main purposes are to (1)
      distribute a set of BG Monitor data into 8 risk zones ranging from none to
      extreme and (2) present the data in a color coded display to promote
      visualization. Besides aggregating the data into 8 zones corresponding to levels
      of risk, the SEG computes the number and percentage of data pairs in each zone
      and the number/percentage of data pairs above/below the diagonal line in each
      zone, which are associated with BGM errors creating risks for hypo- or
      hyperglycemia, respectively. To illustrate the action of the SEG software we
      first present computer-simulated data stratified along error levels defined by
      ISO 15197:2013. This allows the SEG to be linked to this established standard.
      Further illustration of the SEG procedure is done with a series of previously
      published data, which reflect the performance of BGM devices and test strips
      under various environmental conditions. We conclude that the SEG software is a
      useful addition to the SEG analysis presented in this journal, developed to
      assess the magnitude of clinical risk from analytically inaccurate data in a
      variety of high-impact situations such as intensive care and disaster settings. 

PMID- 25562888
TI  - A computational proof of concept of a machine-intelligent artificial pancreas
      using Lyapunov stability and differential game theory.
AB  - BACKGROUND: This study demonstrated the novel application of a "machine
      intelligent" mathematical structure, combining differential game theory and
      Lyapunov-based control theory, to the artificial pancreas to handle dynamic
      uncertainties. METHODS: Realistic type 1 diabetes (T1D) models from the
      literature were combined into a composite system. Using a mixture of "black box"
      simulations and actual data from diabetic medical histories, realistic sets of
      diabetic time series were constructed for blood glucose (BG), interstitial fluid
      glucose, infused insulin, meal estimates, and sometimes plasma insulin assays.
      The problem of underdetermined parameters was side stepped by applying a variant
      of a genetic algorithm to partial information, whereby multiple candidate
      personalized models were constructed and then rigorously tested using further
      data. These formed a "dynamic envelope" of trajectories in state space, where
      each trajectory was generated by a hypothesis on the hidden T1D system dynamics.
      This dynamic envelope was then culled to a reduced form to cover observed dynamic
      behavior. A machine-intelligent autonomous algorithm then implemented game theory
      to construct real-time insulin infusion strategies, based on the flow of these
      trajectories through state space and their interactions with hypoglycemic or near
      hyperglycemic states. RESULTS: This technique was tested on 2 simulated
      participants over a total of fifty-five 24-hour days, with no hypoglycemic or
      hyperglycemic events, despite significant uncertainties from using actual
      diabetic meal histories with 10-minute warnings. In the main case studies, BG was
      steered within the desired target set for 99.8% of a 16-hour daily assessment
      period. Tests confirmed algorithm robustness for +/-25% carbohydrate error. For
      over 99% of the overall 55-day simulation period, either formal controller
      stability was achieved to the desired target or else the trajectory was within
      the desired target. CONCLUSIONS: These results suggest that this is a stable,
      high-confidence way to generate closed-loop insulin infusion strategies.

PMID- 25562890
TI  - Another opinion   on the AVMA policy   on veterinary dentistry.

PMID- 25562889
TI  - Using the widely available blood glucose meter to monitor insulin and HbA1c.
AB  - The blood glucose meter (BGM) is the most successful and widely used portable
      device for point-of-care (POC) tests. However, its usage is limited to self
      monitoring of blood glucose level only. To expand the targets that BGM can
      monitor while taking advantage of more than 50 years of technology development,
      we report herein the use of BGM to detect and quantify insulin and glycated
      hemoglobin (HbA1c), which are useful hormone for diabetes treatment and biomarker
      for diabetes monitoring, respectively. The method is based on invertase enzyme
      linked immunosorbent assay (iELISA) and phosphatase enzyme-linked immunosorbent
      assay (pELISA) that convert BGM-inert sucrose or glucose-1-phosphate into glucose
      in the presence of insulin and glycated hemoglobin, respectively. In both assays,
      monoclonal antibodies specific to the targets (insulin or HbA1c) are immobilized
      onto magnetic beads to capture the targets in samples, followed by the formation
      of sandwich complex with the polyclonal antibodies conjugated to either invertase
      or phosphatase. The quantification of the targets is then realized by the
      production of glucose from the biochemical reactions catalyzed by the polyclonal
      antibody-enzyme conjugates bound on the surface of the magnetic beads. Such a
      method can be generally applied to a wide range of other biomarkers using the
      corresponding antibodies. 

PMID- 25562891
TI  - Reply to letter to the editor: "Right-sided double-lumen tubes: need for design
      improvement and better insertion technique?" by Bussieres et al.

PMID- 25562892
TI  - In Memoriam:   Donald N. Ross  (1922-2014).

PMID- 25562893
TI  - Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); TRICARE
      Retired Reserve. Final rule.
AB  - TRICARE Retired Reserve (TRR) is a premium-based TRICARE health plan available
      for purchase worldwide by qualified members of the Retired Reserve and by
      qualified survivors of TRR members. This final rule responds to public comments
      received to an interim final rule that was published in the Federal Register on
      August 6, 2010 (75 FR 47452-47457). That rule established requirements and
      procedures to implement the TRR program in fulfillment of section 705 of the
      National Defense Authorization Act for Fiscal Year 2010 (NDAA-10) (Pub. L. 111
      84). This final rule also revises requirements and procedures as indicated.

PMID- 25562894
TI  - TRICARE; coverage of care related to non-covered initial surgery or treatment.
      Final rule.
AB  - This final rule revises the limitations on certain TRICARE basic program
      benefits. More specifically, it allows coverage for otherwise covered services
      and supplies required in the treatment of complications (unfortunate sequelae),
      as well as medically necessary and appropriate follow-on care, resulting from a
      non-covered incident of treatment provided pursuant to a properly granted
      Supplemental Health Care Program waiver. This final rule amends two provisions of
      the TRICARE regulations which limits coverage for the treatment of complications
      resulting from a non-covered incident of treatment, and which expressly excludes
      from coverage in the Basic Program services and supplies related to a non-covered
      condition or treatment.

PMID- 25562895
TI  - TRICARE program; clarification of benefit coverage of durable equipment and
      ordering or prescribing durable equipment; clarification of benefit coverage of
      assistive technology devises under the Extended Care Health Option Program. Final
      rule.
AB  - This final rule modifies the TRICARE regulation to add a definition of assistive
      technology (AT) devices for purposes of benefit coverage under the TRICARE
      Extended Care Health Option (ECHO) Program and to amend the definitions of
      durable equipment (DE) and durable medical equipment (DME) to better conform the
      language in the regulation to the statute. The final rule amends the language
      that specifically limits ordering or prescribing of DME to only a physician under
      the Basic Program, as this amendment will allow certain other TRICARE authorized
      individual professional providers, acting within the scope of their licensure, to
      order or prescribe DME. This final rule also incorporates a policy clarification
      relating to luxury, deluxe, or immaterial features of equipment or devices. That
      is, TRICARE cannot reimburse for the luxury, deluxe, or immaterial features of
      equipment or devices, but can reimburse for the base or basic equipment or device
      that meet the beneficiary's needs. Beneficiaries may choose to pay the provider
      for the luxury, deluxe, or immaterial features if they desire their equipment or
      device to have these "extra features."

PMID- 25562896
TI  - Additional requirements for charitable hospitals; community health needs
      assessments for charitable hospitals; requirement of a section 4959 excise tax
      return and time for filing the return. Final regulations and removal of temporary
      regulations.
AB  - This document contains final regulations that provide guidance regarding the
      requirements for charitable hospital organizations added by the Patient
      Protection and Affordable Care Act of 2010. The regulations will affect
      charitable hospital organizations

PMID- 25562897
TI  - Extension of expiration dates for several body system listings. Final rule.
AB  - We are extending the expiration dates of the following body systems in the
      Listing of Impairments (listings) in our regulations: Growth Impairment,
      Musculoskeletal System, Respiratory System, Cardiovascular System, Digestive
      System, Hematological Disorders, Skin Disorders, Neurological, and Mental
      Disorders. We are making no other revisions to these body systems in this final
      rule. This extension will ensure that we continue to have the criteria we need to
      evaluate impairments in the affected body systems at step three of the sequential
      evaluation processes for initial claims and continuing disability reviews.

PMID- 25562898
TI  - Revisions to direct fee payment rules. Final rules.
AB  - We are adopting, with two revisions, our interim final rules that implemented
      amendments to the Social Security Act (Act) made by the Social Security
      Disability Applicants' Access to Professional Representation Act of 2010 (PRA).
      The interim final rules made permanent the direct fee payment rules for eligible
      non-attorney representatives under titles II and XVI of the Act and for attorney
      representatives under title XVI of the Act. They also revised some of our
      eligibility policies for non-attorney representatives under titles II and XVI of
      the Act. Based on public comment and subsequent inquiries, we are revising our
      rules to clarify that an eligible non-attorney representative's liability
      insurance policy must include malpractice coverage. We are also reaffirming that
      a business entity legally permitted to provide the required insurance in the
      States in which the non-attorney representative conducts business must underwrite
      the policies.

PMID- 25562900
TI  - [What is the future of psychiatry?].

PMID- 25562899
TI  - [Toward alternative solutions].

PMID- 25562901
TI  - [Benzodiazepines, risk factors for Alzheimer disease].

PMID- 25562903
TI  - [Hallucinatory commands and cognitive therapy].

PMID- 25562902
TI  - [Geriatric psychiatry: chronicle of an imminent boom].

PMID- 25562904
TI  - [Facilitating access for intellectually disabled persons to mental health
      services].

PMID- 25562905
TI  - [Asperger syndrome: increased suicidal ideation].

PMID- 25562906
TI  - [First edition of Mad Days].

PMID- 25562907
TI  - [Mental disorders: a much higher mortality rate than the general population].

PMID- 25562909
TI  - [The art of psychological containment in nursing care].

PMID- 25562908
TI  - [When psychiatry was an affair of the heart].

PMID- 25562910
TI  - [Containment as a psychological process].
AB  - To move away from the clinical simplification of the term and restore its full
      complexity, it is possible to approach the notion of containment through the
      prism of psychological processuality. Beyond the theory, the caregiver's
      experience in their practice and in their contact with the patient can be
      considered on the basis of a series of standpoints which form the sphere of the
      "capacity of internal containment". However, containment is not the be all and
      end all of care. Containment has its limits and care must also be viewed as a
      constellation of complementary processes.

PMID- 25562911
TI  - [Psychological containment put to the test by a crisis].
AB  - In the first-time admission unit, psychological containment is based essentially
      on receivingthe patient in crisis. While the management of the crisis is
      inseparable from containment, the drawing up of the patient's history, centred on
      observation, transfer and the clinical aspect, is a key stage in the patient's
      care. In an institution, the nursing team will, through its creativity, invent
      the care, seeking a possible alliance.

PMID- 25562912
TI  - [Once upon a time, there was...the nurse in adult psychiatry].
AB  - While nursing in psychiatry is based essentially on the relational aspect,
      learning the "containment function" is a long-term undertaking. It is through
      their successive confrontations with care situations that nurses build up a solid
      experience. The progression of their thought process will then enable them to
      share their practices and their experience.

PMID- 25562916
TI  - [Psychological containment at home].
AB  - The mobile care and rehabilitation team offers patients who have been receiving
      long-term, in-patient care, when they are stabilised, a discharge programme
      underpinned by considerable support from a nursing team. Through apartments owned
      by associations and the CATTP (part-time therapy centre), the team will guide the
      patient along their sometimes precarious pathway. This well thought-out and
      shared support, takes on the function of psychological containment for the
      patient, helping to ensure a successful reintegration.

PMID- 25562917
TI  - [Management, a containment tool].
AB  - Healthcare managers, in partnership with a doctor, are responsible for the care
      project, the coherence of the care activities and the cohesion of the team. Their
      managerial role means they need to be receptive to and contain the feelings of
      the team, as well as take an active part in the psychological containment
      approach used with the patient.

PMID- 25562918
TI  - [Bibliography].

PMID- 25562919
TI  - [Listening to children through drawings in transcultural consultations].
AB  - The transcultural consultation is a form of group therapy which is aimed at
      families from other countries, using a method which enables children, through
      drawing, to express themselves in a group. The favoured means of communication
      for children, drawing is an effective way of liberatingthoughts and giving
      meaning to family history. Incorporated into the overall narrative, it can
      thereby be a form of mediation, on condition that it is integrated into the
      therapeutic programme. This article reflects on the characteristics of the
      drawings produced by these children who have different cultures and different
      ways of drawing.

PMID- 25562921
TI  - [Paul-Claude Racamier].

PMID- 25562920
TI  - [Consultations with a nurse specialized in cognitive behavioural therapies].
AB  - Cognitive behavioural therapies (CBT), which have been proven to be effective,
      are tools which are simple to use and implement. In Sainte Anne hospital,
      consultations with a nurse specialised in CBT were first set up in 2011.The nurse
      specialised in CBT sees the patients on a one-to-one basis and often plays,
      within the multidisciplinary team, the role of care coordinator.

PMID- 25562922
TI  - [Cutaneous eruptions related to infectious diseases in children: guidelines for
      community pharmacists].
AB  - This article discusses some infectious diseases characterized by eruptions,
      frequently seen in children. Based on the symptoms, the pharmacy team is able to
      know the possible cause of the eruptions, to refer if necessary, and to optimize
      the pharmaceutical care for the patients. Besides general advice regarding
      eruption and fever, specific advice is given for each disease focusing on
      hygienic measures and prevention of further infection.

PMID- 25562923
TI  - [Acute lymphoblastic leukemia in children: history of drug therapy management].
AB  - The last forty years have witnessed major improvements in the survival of
      pediatric cancer patients with an evolution of acute tymphoblastic leukemia as an
      untreatable disease to acute lymphoblastic leukemia with a survival rate of more
      than 90%. This has become possible due to improvements in the various modalities
      of cancer therapy and supportive care. The aim of this commentary is to give an
      overview of the history of pharmacological treatment for children with acute
      Lymphoblastic leukemia.

PMID- 25562924
TI  - [Nasal administration of fentanyl: prevention of medication-related errors by
      using REMED-method].
AB  - REMED stands for a "MEDication Errors Review". The REMED method aims at
      implementing and monitoring actions to improve patient medical care. This
      approach is part of the continuing healthcare quality and safety improvement and
      professional practice evaluation. REMED uses methodology and tools. Thus we use
      this methodology in the context of a drug errorwhich occurred in the dermatology
      department of our hospital. After this event description, related to a sensitive
      drug product, Instanyl (transmucosal fentanyl), the drug error is described, then
      the different causes are analyzed. These last are numerous and occur at any stage
      of patient medical care. They must allow us to show actions in order to improve
      patients' safety.

PMID- 25562925
TI  - [The use of intrauterine device in nulliparous over 18 years: a Belgian
      consensus].
AB  - Under the presidency of prof. H. Depypere (UZ Ghent) and Prof. P. Simon (ULB
      Erasme) a Belgian panel of thirteen experts (gynecologists, representatives of
      universities and scientific associations for gynecology-obstetrics) reached a
      consensus on the use of intrauterine systems, both copper IUDs as hormone IUDs,
      in nultiparous women.

PMID- 25562926
TI  - Incentives for market penetration of biosimilars in Belgium and in five European
      countries.
AB  - Biosimilars are products similar to a biological already authorized and no longer
      protected by a patent. As the biological product, they contain a biological
      substance produced by or derived from a living organism. Alike with generics,
      biosimilars are potential tool to ensure savings for health systems. The current
      lack of market penetration of biosimilars may be seen by national authorities as
      a lost opportunity in terms of cost- containment. The objective of this paper is
      therefore to analyze the current situation in Belgium and to identify potential
      measures to stimulate biosimilar uptake in Belgium through an analysis of the
      experience in five European countries: France, Germany, The Netherlands, Spain
      and Sweden. This international comparison was performed using a two steps
      analysis: a structured review of the literature followed by a validation from
      experts in each country. Potential incentives and constraints were identified,
      i.e., prescription quotas/target, clinical guidelines, primary substitution,
      reference price system, fixed payment and public tendering. However, the
      literature reviewed provided little evaluation of the effectiveness of these
      policies in terms of biosimilar uptake or potential savings. The impact of these
      policies on biosimilar related savings is currently based on expectation and
      assumptions. Such kind of studies is therefore essential in the future.

PMID- 25562927
TI  - [Tetrabenazine (tetrabenazine Orphan) orally].

PMID- 25562928
TI  - [Nalmefene (Selincro) orally].

PMID- 25562929
TI  - [Capsaicin (QUTENZA), dermatological use].

PMID- 25562930
TI  - Analysis and discussion on formation and control of primary particulate matter
      generated from coal-fired power plants.
AB  - Particulate matter (PM) has been becoming the principal urban pollutant in many
      major cities in China, and even all over the world. It is reported that the coal
      combustion process is one of the main sources of PM in the atmosphere. Therefore,
      an investigation of formation and emission of fine primary PM in coal combustion
      was conducted. First, the sources and classification of coal-fired primary PM
      were discussed; then their formation pathways during the coal combustion process
      were analyzed in detail. Accordingly, the emission control methods for fine
      particles generated from coal-fired power plants were put forward, and were
      classified as precombustion control, in-combustion control, and postcombustion
      control. Precombustion control refers to the processes for improving the coal
      quality before combustion, such as coal type selection and coal preparation. In
      combustion control means to take measures for adjusting the combustion conditions
      and injection of additives during the combustion process to abate the formation
      of PM. Postcombustion control is the way that the fine PM are aggregated into
      larger ones by some agglomeration approaches and subsequently are removed by dust
      removal devices, or some high-performance modifications of conventional particle
      emission control devices (PECDs) can be taken for capturing fine particles.
      Finally, some general management suggestions are given for reducing fine PM
      emission in coal-fired power plants. Implications: The analysis and discussions
      of coal properties and its combustion process are critical to recognizing the
      formation and emission of the fine primary PM in combustion. The measures of
      precombustion, in-combustion, and postcombustion control based on the analysis
      and discussions are favorable for abating the PM emission. Practically, some
      measures of implementation do need the support of national policies, even needing
      to sacrifice economy to gain environmental profit, but this is the very time to
      execute these, and high-performances PECDs, especially novel devices, should be
      used for removing fine PM in flue gas.

PMID- 25562931
TI  - PM10 concentration levels at an urban and background site in Cyprus: the impact
      of urban sources and dust storms.
AB  - Air quality in Cyprus is influenced by both local and transported pollution,
      including desert dust storms. We examined PM10 concentration data collected in
      Nicosia (urban representative) from April 1, 1993, through December 11, 2008, and
      in Ayia Marina (rural background representative) from January 1, 1999, through
      December 31, 2008. Measurements were conducted using a Tapered Element
      Oscillating Micro-balance (TEOM). PM10 concentrations, meteorological records,
      and satellite data were used to identify dust storm days. We investigated long
      term trends using a Generalized Additive Model (GAM) after controlling for day of
      week, month, temperature, wind speed, and relative humidity. In Nicosia, annual
      PM10 concentrations ranged from 50.4 to 63.8 MUg/m3 and exceeded the EU annual
      standard limit enacted in 2005 of 40 MUg/m3 every year A large, statistically
      significant impact of urban sources (defined as the difference between urban and
      background levels) was seen in Nicosia over the period 2000-2008, and was highest
      during traffic hours, weekdays, cold months, and low wind conditions. Our
      estimate of the mean (standard error) contribution of urban sources to the daily
      ambient PM10 was 24.0 (0.4) MUg/m3. The study of yearly trends showed that PM10
      levels in Nicosia decreased from 59.4 MUg/m3 in 1993 to 49.0 MUg/m3 in 2008,
      probably in part as a result of traffic emission control policies in Cyprus. In
      Ayia Marina, annual concentrations ranged from 27.3 to 35.6 MUg/m3, and no
      obvious time trends were observed. The levels measured at the Cyprus background
      site are comparable to background concentrations reported in other Eastern
      Mediterranean countries. Average daily PM10 concentrations during desert dust
      storms were around 100 MUg/m3 since 2000 and much higher in earlier years.
      Despite the large impact ofdust storms and their increasing frequency over time,
      dust storms were responsible for a small fraction of the exceedances of the daily
      PM10 limit. Implications: This paper examines PM10 concentrations in Nicosia,
      Cyprus, from 1993 to 2008. The decrease in PM10 levels in Nicosia suggests that
      the implementation of traffic emission control policies in Cyprus has been
      effective. However, particle levels still exceeded the European Uion annual
      standard, and dust storms were responsible for a small fraction of the daily PM10
      limit exceedances. Other natural particles that are not assessed in this study,
      such as resuspended soil and sea salt, may be responsible in part for the hig
      particle levels.

PMID- 25562932
TI  - Identification of the sources of PM10 in a subway tunnel using positive matrix
      factorization.
AB  - The level of particulate matter of less than 10 MUm diameter (PM10) at subway
      platforms can be significantly reduced by installing a platform screen-door
      system. However, both workers and passengers might be exposed to higher PM10
      levels while the cars are within the tunnel because it is a more confined
      environment. This study determined the PM10 levels in a subway tunnel, and
      identified the sources of PM10 using elemental analysis and receptor modeling.
      Forty-four PM10 samples were collected in the tunnel between the Gireum and Mia
      stations on Line 4 in metropolitan Seoul and analyzed using inductively coupled
      plasma-atomic emission spectrometry and ion chromatography. The major PM10
      sources were identified using positive matrix factorization (PMF). The average
      PM10 concentration in the tunnels was 200.8 +/- 22.0 MUg/m3. Elemental analysis
      indicated that the PM10 consisted of 40.4% inorganic species, 9.1% anions, 4.9%
      cations, and 45.6% other materials. Iron was the most abundant element, with an
      average concentration of 72.5 +/- 10.4 MUg/m3. The PM10 sources characterized by
      PMF included rail, wheel, and brake wear (59.6%), soil combustion (17.0%),
      secondary aerosols (10.0%), electric cable wear (8.1%), and soil and road dust
      (5.4%). Internal sources comprising rail, wheel, brake, and electric cable wear
      made the greatest contribution to the PM10 (67.7%) in tunnel air. Implications:
      With installation of a platform screen door, PM10 levels in subway tunnels were
      higher than those on platforms. Tunnel PM10 levels exceeded 150 ug/m3 of the
      Korean standard for subway platform. Elemental analysis of PM10 in a tunnel
      showed that Fe was the most abundant element. Five PM10 sources in tunnel were
      identified by positive matrix factorization. Railroad-related sources contributed
      68% of PM10 in the subway tunnel.

PMID- 25562933
TI  - Impact of emissions from natural gas production facilities on ambient air quality
      in the Barnett Shale area: a pilot study.
AB  - Rapid and extensive development of shale gas resources in the Barnett Shale
      region of Texas in recent years has created concerns about potential
      environmental impacts on water and air quality. The purpose of this study was to
      provide a better understanding of the potential contributions of emissions from
      gas production operations to population exposure to air toxics in the Barnett
      Shale region. This goal was approached using a combination of chemical
      characterization of the volatile organic compound (VOC) emissions from active
      wells, saturation monitoring for gaseous and particulate pollutants in a
      residential community located near active gas/oil extraction and processing
      facilities, source apportionment of VOCs measured in the community using the
      Chemical Mass Balance (CMB) receptor model, and direct measurements of the
      pollutant gradient downwind of a gas well with high VOC emissions. Overall, the
      study results indicate that air quality impacts due to individual gas wells and
      compressor stations are not likely to be discernible beyond a distance of
      approximately 100 m in the downwind direction. However, source apportionment
      results indicate a significant contribution to regional VOCs from gas production
      sources, particularly for lower-molecular-weight alkanes (< C6). Although
      measured ambient VOC concentrations were well below health-based safe exposure
      levels, the existence of urban-level mean concentrations of benzene and other
      mobile source air toxics combined with soot to total carbon ratios that were high
      for an area with little residential or commercial development may be indicative
      of the impact of increased heavy-duty vehicle traffic related to gas production.
      Implications: Rapid and extensive development of shale gas resources in recent
      years has created concerns about potential environmental impacts on water and air
      quality. This study focused on directly measuring the ambient air pollutant
      levels occurring at residential properties located near natural gas extraction
      and processing facilities, and estimating the relative contributions from gas
      production and motor vehicle emissions to ambient VOC concentrations. Although
      only a small-scale case study, the results may be useful for guidance in planning
      future ambient air quality studies and human exposure estimates in areas of
      intensive shale gas production.

PMID- 25562934
TI  - Thermal conductivity characteristics of dewatered sewage sludge by thermal
      hydrolysis reaction.
AB  - The purpose of this study is to quantify the thermal conductivity of sewage
      sludge related to reaction temperature for the optimal design of a thermal
      hydrolysis reactor. We continuously quantified the thermal conductivity of
      dewatered sludge related to the reaction temperature. As the reaction temperature
      increased, the dewatered sludge is thermally liquefied under high temperature and
      pressure by the thermal hydrolysis reaction. Therefore, the bound water in the
      sludge cells comes out as free water, which changes the dewatered sludge from a
      solid phase to slurry in a liquid phase. As a result, the thermal conductivity of
      the sludge was more than 2.64 times lower than that of the water at 20. However,
      above 200, it became 0.704 W/m* degrees C, which is about 4% higher than that of
      water. As a result, the change in physical properties due to thermal hydrolysis
      appears to be an important factor for heat transfer efficiency. Implications: The
      thermal conductivity of dewatered sludge is an important factor the optimal
      design of a thermal hydrolysis reactor. The dewatered sludge is thermally
      liquefied under high temperature and pressure by the thermal hydrolysis reaction.
      The liquid phase slurry has a higher thermal conductivity than pure water.

PMID- 25562935
TI  - Emissions variability processor (EMVAP): design, evaluation, and application.
AB  - Emissions of pollutants such as SO2 and NOx from external combustion sources can
      vary widely depending on fuel sulfur content, load, and transient conditions such
      as startup, shutdown, and maintenance/malfunction. While monitoring will
      automatically reflect variability from both emissions and meteorological
      influences, dispersion modeling has been typically conducted with a single
      constant peak emission rate. To respond to the need to account for emissions
      variability in addressing probabilistic 1-hr ambient air quality standards for
      SO2 and NO2, we have developed a statistical technique, the Emissions Variability
      Processor (EMVAP), which can account for emissions variability in dispersion
      modeling through Monte Carlo sampling from a specified frequency distribution of
      emission rates. Based upon initial AERMOD modeling of from 1 to 5 years of actual
      meteorological conditions, EMVAP is used as a postprocessor to AERMOD to simulate
      hundreds or even thousands of years of concentration predictions. This procedure
      uses emissions varied hourly with a Monte Carlo sampling process that is based
      upon the user-specified emissions distribution, from which a probabilistic
      estimate can be obtained of the controlling concentration. EMVAP can also
      accommodate an advanced Tier 2 NO2 modeling technique that uses a varying ambient
      ratio method approach to determine the fraction of total oxides of nitrogen that
      are in the form of nitrogen dioxide. For the case of the 1-hr National Ambient
      Air Quality Standards (NAAQS, established for SO2 and NO2), a "critical value"
      can be defined as the highest hourly emission rate that would be simulated to
      satisfy the standard using air dispersion models assuming constant emissions
      throughout the simulation. The critical value can be used as the starting point
      for a procedure like EMVAP that evaluates the impact of emissions variability and
      uses this information to determine an appropriate value to use for a longer-term
      (e.g., 30-day) average emission rate that would still provide protection for the
      NAAQS under consideration. This paper reports on the design of EMVAP and its
      evaluation on several field databases that demonstrate that EMVAP produces a
      suitably modest overestimation of design concentrations. We also provide an
      example of an EMVAP application that involves a case in which a new emission
      limitation needs to be considered for a hypothetical emission unit that has
      infrequent higher-than-normal SO2 emissions. Implications: Emissions of
      pollutants from combustion sources can vary widely depending on fuel sulfur
      content, load, and transient conditions such as startup and shutdown. While
      monitoring will automatically reflect this variability on measured
      concentrations, dispersion modeling is typically conducted with a single peak
      emission rate assumed to occur continuously. To realistically account for
      emissions variability in addressing probabilistic 1-hr ambient air quality
      standards for SO2 and NO2, the authors have developed a statistical technique,
      the Emissions Variability Processor (EMVAP), which can account for emissions
      variability in dispersion modeling through Monte Carlo sampling from a specified
      frequency distribution of emission rates.

PMID- 25562936
TI  - A hybrid biological process of indoor air treatment for toluene removal.
AB  - Bioprocesses, such as biofiltration, are commonly used to treat industrial
      effluents containing volatile organic compounds (VOCs) at low concentrations.
      Nevertheless, the use of biofiltration for indoor air pollution (IAP) treatment
      requires adjustments depending on specific indoor environments. Therefore, this
      study focuses on the convenience of a hybrid biological process for IAP
      treatment. A biofiltration reactor using a green waste compost was combined with
      an adsorption column filled with activated carbon (AC). This system treated a
      toluene-micropolluted effluent (concentration between 17 and 52 MUg/m3),
      exhibiting concentration peaks close to 733 MUg/m3 for a few hours per day. High
      removal efficiency was obtained despite changes in toluene inlet load (from 4.2 x
      10(-3) to 0.20 g/m3/hr), which proves the hybrid system's effectiveness. In fact,
      during unexpected concentration changes, the efficiency of the biofilter is
      greatly decreased, but the adsorption column maintains the high efficiency of the
      entire process (removal efficiency [RE] close to 100%). Moreover, the adsorption
      column after biofiltration is able to deal with the problem of the emission of
      particles and/or microorganisms from the biofilter. Implications: Indoor air
      pollution is nowadays recognized as major environmental and health issue. This
      original study investigates the performance of a hybrid biological process
      combining a biofilter and an adsorption column for removal of indoor VOCs,
      specifically toluene.

PMID- 25562937
TI  - U.S. national PM2.5 Chemical Speciation Monitoring Networks-CSN and IMPROVE:
      description of networks.
AB  - The US. EnvironmentalProtection Agency (EPA) initiated the national PM2.5
      Chemical Speciation Monitoring Network (CSN) in 2000 to support evaluation of
      long-term trends and to better quantify the impact of sources on particulate
      matter (PM) concentrations in the size range below 2.5 MUm aerodynamic diameter
      (PM2.5; fine particles). The network peaked at more than 260 sites in 2005. In
      response to the 1999 Regional Haze Rule and the need to better understand the
      regional transport of PM, EPA also augmented the long-existing Interagency
      Monitoring of Protected Visual Environments (IMPROVE) visibility monitoring
      network in 2000, adding nearly 100 additional IMPROVE sites in rural Class 1
      Areas across the country. Both networks measure the major chemical components of
      PM2.5 using historically accepted filter-based methods. Components measured by
      both networks include major anions, carbonaceous material, and a series of trace
      elements. CSN also measures ammonium and other cations directly, whereas IMPROVE
      estimates ammonium assuming complete neutralization of the measured sulfate and
      nitrate. IMPROVE also measures chloride and nitrite. In general, the field and
      laboratory approaches used in the two networks are similar; however, there are
      numerous, often subtle differences in sampling and chemical analysis methods,
      shipping, and quality control practices. These could potentially affect merging
      the two data sets when used to understand better the impact of sources on PM
      concentrations and the regional nature and long-range transport of PM2zs. This
      paper describes, for the first time in the peer-reviewed literature, these
      networks as they have existed since 2000, outlines differences infield and
      laboratory approaches, provides a summary of the analytical parameters that
      address data uncertainty, and summarizes major network changes since the
      inception of CSN. Implications: Two long-term chemical speciation particle
      monitoring networks have operated simultaneously in the United States since 2001,
      when the EPA began regular operations of its PM2.5 Chemical Speciation Monitoring
      Network (IMPROVE began in 1988). These networks use similar field sampling and
      analytical methods, but there are numerous, often subtle differences in equipment
      and methodologies that can affect the results. This paper describes these
      networks since 20000 (inception of CSN) and their differences, and summarizes the
      analytical parameters that address data uncertainty, providing researches and
      policymakers with background information they may need (e.g., for 2018 PM2.5
      designation and State Implementation Plan process; McCarthy, 2013) to assess
      results from each network and decide how these data sets can be mutually employed
      for enhanced analyses. Changes in CSN and IMPROVE that have occurred over the
      years also are described.

PMID- 25562938
TI  - Trivalent chromium solubility and its influence on quantification of hexavalent
      chromium in ambient particulate matter using EPA method 6800.
AB  - Measurement of carcinogenic Cr(VI) in ambient PM is challenging due to potential
      errors associated with conversion between Cr (VI) (a carcinogen) and Cr(III) (an
      essential nutrient). Cr(III) conversion is a particular concern due to its > 80%
      atomic abundance in total Cr. US. Environmental Protection Agency (EPA) method
      6800 that uses water-soluble isotope spikes can be used to correct the
      interconversion. However, whether the enriched Cr(III) isotope spikes can
      adequately mimic the Cr(III) species originally in ambient PM is unknown. This
      study examined the water solubility of Cr(III) in ambient PM and discussed its
      influence on Cr(VI) measurement. Ambient PM10 samples were collected on Teflon
      filters at four sites in New Jersey that may have different Cr emission sources.
      The samples were ultrasonically extracted with 5 mL DI-H2O (pH 5.7) at room
      temperature for 40 min, and then analyzed by ion chromatography-inductively
      coupled plasma mass spectrometry (IC-ICPMS). Cr(III) was below detection limit
      (0.06 ng/m3) for all samples, suggesting water-soluble Cr(III) species, such as
      CrCl3, Cr(NO3)3, and amorphous Cr(OH)3, in the ambient PM were negligible.
      Therefore, the enriched 50Cr(III) isotope spike (in the form of Cr(NO3)3) could
      not mimic the original ambient Cr(III). Only the conversion of 53Cr(VI) (in the
      form of K2CrO4) was taken into account when correcting the interconversion. We
      then used NaHCO3-pretreated MCE filters (prespiked with enriched isotope species)
      to measure Cr(VI) in the ambient PM10. The samples were ultrasonically extracted
      at 60 C pH 9 solutions for 40 min followed by IC-ICPMS analysis. Due to the
      correction of Cr(VI) reduction, the Cr(VI) concentrations determined by EPA
      method 6800, 0.26 +/- 0.16 (summer) and 0.16 +/- 0.11(winter) ng/m3 (n = 64),
      were significantly greater than those by the external standard curve, 0.21 +/-
      0.17 (summer) and 0.10 +/- 0.07 (winter) ng/m3 (n = 56) (p < 0.01, Student's t
      test). Our study revealed that appropriate application of EPA method 6800 is
      important because it only applies to soluble fraction of Cr species in ambient
      PM. Implications: Accurate measurement of carcinogenic Cr(VI) in ambient PM is
      challenging due to conversion between Cr(VI) (a human carcinogen) and Cr(III) (a
      human essential nutrient). The conversion of CR(III) is of particular concern due
      to its dominant presence in total Cr (>80%). This study examined the water
      solubility of Cr(III) in ambient PM that was collected at four locations in New
      Jersey. Then we discussed the influence of Cr(III) solubility on the application
      of EPA method 6800, which utilizes enriched isotope spikes to correct the
      interconversion. Our results suggested that appropriate application of EPA method
      6800 is important because it only applies to soluble fraction of Cr species.

PMID- 25562939
TI  - Diving deeper and higher: an editorial perspective.

PMID- 25562940
TI  - Dysbaric osteonecrosis in divers: an editorial perspective.

PMID- 25562941
TI  - Diving at altitude: from definition to practice.
AB  - Diving above sea level has different motivations for recreational, military,
      commercial and scientific activities. Despite the apparently wide practice of
      inland diving, there are three major discrepancies about diving at altitude:
      threshold elevation that requires changes in sea level procedures; upper altitude
      limit of the applicability of these modifications; and independent validation of
      altitude adaptation methods of decompression algorithms. The first problem is
      solved by converting the normal fluctuation in barometric pressure to an altitude
      equivalent. Based on the barometric variations recorded from a meteorological
      center, it is possible to suggest 600 meters as a threshold for classifying a
      dive as an "altitude" dive. The second problem is solved by proposing the
      threshold altitude of aviation (2,400 meters) to classify "high" altitude dives.
      The DAN (Divers Alert Network) Europe diving database (DB) is analyzed to solve
      the third problem. The database consists of 65,050 dives collected from different
      dive computers. A total of 1,467 dives were found to be classified as altitude
      dives. However, by checking the elevation according to the logged geographical
      coordinates, 1,284 dives were disqualified because the altitude setting had been
      used as a conservative setting by the dive computer despite the fact that the
      dive was made at sea level. Furthermore, according to the description put forward
      in this manuscript, 72 dives were disqualified because the surface level
      elevation is lower than 600 meters. The number of field data (111 dives) is still
      very low to use for the validation of any particular method of altitude
      adaptation concerning decompression algorithms.

PMID- 25562942
TI  - Decompression tables for inside chamber attendants working at altitude.
AB  - INTRODUCTION: Hyperbaric oxygen (HBO2) multiplace chamber inside attendants (IAs)
      are at risk for decompression sickness (DCS). Standard decompression tables are
      formulated for sea-level use, not for use at altitude. METHODS: At
      Presbyterian/St. Luke's Medical Center (Denver, Colorado, 5,924 feet above sea
      level) and Intermountain Medical Center (Murray, Utah, 4,500 feet), the
      decompression obligation for IAs is managed with U.S. Navy Standard Air Tables
      corrected for altitude, Buhlmann Tables, and the Nobendem(c) calculator. IAs also
      breathe supplemental oxygen while compressed. Presbyterian/St. Luke's (0.83
      atmospheres absolute/atm abs) uses gauge pressure, uncorrected for altitude, at
      45 feet of sea water (fsw) (2.2 atm abs) for routine wound care HBO2 and 66 fsw
      (2.8 atm abs) for carbon monoxide/cyanide poisoning. Presbyterian/St. Luke's
      provides oxygen breathing for the IAs at 2.2 atm abs. At Intermountain (0.86 atm
      abs), HBO2 is provided at 2.0 atm abs for routine treatments and 3.0 atm abs for
      carbon monoxide poisoning. Intermountain IAs breathe intermittent 50%
      nitrogen/50% oxygen at 3.0 atm abs and 100% oxygen at 2.0 atm abs. The chamber
      profiles include a safety stop. RESULTS: From 1990-2013, Presbyterian/St. Luke's
      had 26,900 total IA exposures: 25,991 at 45 fsw (2.2 atm abs) and 646 at 66 fsw
      (2.8 atm abs); there have been four cases of IA DCS. From 2008-2013,
      Intermountain had 1,847 IA exposures: 1,832 at 2 atm abs and 15 at 3 atm abs,
      with one case of IA DCS. At both facilities, DCS incidents occurred soon after
      the chambers were placed into service. CONCLUSIONS: Based on these results,
      chamber inside attendant risk for DCS at increased altitude is low when the
      inside attendants breathe supplemental oxygen.

PMID- 25562943
TI  - Doppler recordings after diving to depth of 30 meters at high altitude of 4,919
      meters (16,138 feet) during the Tilicho Lake Expedition 2007.
AB  - When going to high altitude (higher than 2,400 meters above mean sea level [about
      8,200 feet]), human physiology is strongly affected by changes in atmospheric
      conditions, including decreased ambient pressure and hypobaric hypoxia, which can
      lead to severe hypoxemia, brain and/or pulmonary edema, negative changes in body
      and blood composition, as well as disturbances in regional microcirculation. When
      adding other factors, such as dehydration, physical exercise and exposure to low
      temperature, it is likely that nitrogen desaturation after diving at such
      environmental conditions is far from optimal, There are only single reports on
      diving at high alti-tudes. In 2007 a Polish team of climbers and divers
      participated in the Tilicho Lake and Peak Expedition to the Himalaya Mountains in
      Nepal. During this expedition, four divers conducted six dives in the Tilicho
      Lake at altitude of 4,919 meters above mean sea level equivalent (16,138 feet) to
      a maximum depth of 15 meters of fresh water (mfw) (equivalent to 28 mfw at sea
      level by the Cross Correction method) and 30 mfw (equivalent to 57 mfw at sea
      level "by Cross correction). Decompression debt was calculated using Cross
      Correction with some additional safety add-ons. Precordial Doppler recordings
      were taken every 15 minutes until 90 minutes after surfacing. No signs or
      symptoms of decompression sickness were observed after diving but in one diver,
      very high bubble grade Doppler signals were recorded. It can be concluded that
      diving at high altitude should be accompanied by additional safety precautions as
      well as taking into account personal sensitivity for such conditions.

PMID- 25562944
TI  - A case-control study evaluating relative risk factors for decompression sickness:
      a research report.
AB  - BACKGROUND: Factors contributing to the pathogenesis of decompression sickness
      (DCS) in divers have been described in many studies. However, relative importance
      of these factors has not been reported. METHODS: In this case-control study, we
      compared the diving profiles of divers experiencing DCS with those of a control
      group. The DCS group comprised 35 recreational scuba divers who were diagnosed by
      physicians as having DCS. The control group consisted of 324 apparently healthy
      recreational divers. All divers conducted their dives from 2009 to 2011. The
      questionnaire consisted of 33 items about an individual's diving profile,
      physical condition and activities before, during and just after the dive. To
      simplify dive parameters, the dive site was limited to Izu Osezaki. Odds ratios
      and multiple logistic regression were used for the analysis. RESULTS: Odds ratios
      revealed several items as dive and health factors associated with DCS. The major
      items were as follows: shortness of breath after heavy exercise during the dive
      (OR = 12.12), dehydration (OR = 10.63), and maximum dive depth > 30 msw (OR =
      7.18). Results of logistic regression were similar to those by odds ratio
      analysis. CONCLUSION: We assessed the relative weights of the surveyed dive and
      health factors associated with DCS. Because results of several factors conflict
      with previous studies, future studies are needed.

PMID- 25562945
TI  - Decompression models: review, relevance and validation capabilities.
AB  - INTRODUCTION/BACKGROUND: For more than a century, several types of mathematical
      models have been proposed to describe tissue desaturation mechanisms in order to
      limit decompression sickness. These models are statistically assessed by DCS
      cases, and, over time, have gradually included bubble formation biophysics. This
      paper proposes to review this evolution and discuss its limitations. METHODS:
      This review is organized around the comparison of decompression model biophysical
      criteria and theoretical foundations. Then, the DCS-predictive capability was
      analyzed to assess whether it could be improved by combining different
      approaches. RESULTS: Most of the operational decompression models have a neo
      Haldanian form. Nevertheless, bubble modeling has been gaining popularity, and
      the circulating bubble amount has become a major output. By merging both views,
      it seems possible to build a relevant global decompression model that intends to
      simulate bubble production while predicting DCS risks for all types of exposures
      and decompression profiles. CONCLUSIONS: A statistical approach combining both
      DCS and bubble detection databases has to be developed to calibrate a global
      decompression model. Doppler ultrasound and DCS data are essential: i. to make
      correlation and validation phases reliable; ii. to adjust biophysical criteria to
      fit at best the observed bubble kinetics; and iii. to build a relevant risk
      function.

PMID- 25562946
TI  - Subjective Narcosis Assessment Scale: measuring the subjective experience of
      nitrogen narcosis.
AB  - BACKGROUND: The interaction of subjective experiences and objective measures of
      neuropsychological performance during hyperbaric exposure has received less
      attention in the literature, in part due to the shortage of available and
      appropriately standardized measures. OBJECTIVE: This study aimed to describe the
      psychometric properties of a modified version of the Subjective High Assessment
      Scale when used in the hyperbaric context, by exploring internal reliability,
      factor structure, associations with psychological variables and simple cognitive
      delayed recall, and the effect of task focus on the recall of subjective
      experience. METHOD: Seventy qualified divers completed dry hyperbaric chamber
      dives to 607.95 kPa, and completed ratings of their subjective experiences. Some
      also completed a delayed recall task and psychological measures prior to their
      dives. RESULTS: The scale displayed good internal consistency, with four
      meaningful factors emerging. It showed some significant but small associations
      with trait anxiety and transient mood states, and a small to moderate correlation
      with recall performance. There was no significant effect of task focus on self
      report of subjective experiences. CONCLUSION: The modified scale, renamed the
      Subjective Narcosis Assessment Scale here, has useful psychometric properties,
      and promising potential for future use.

PMID- 25562947
TI  - Commercial diver selection using multiple-criteria decision-making methods.
AB  - INTRODUCTION: Personnel selection for different commercial diving jobs is time
      consuming and subjective, This paper proposes a combination of two multiple
      criteria decision-making (MCDM) methods to provide an objective tool for
      evaluation according to two main selection criteria: work experience and physical
      fitness. METHOD: Subcriteria were computed using the analytic hierarchy process
      (AHP). By consulting two field professionals, subcriteria for work experience
      were determined as: working hours on the project type, hand tools, hydraulic
      tools, pneumatic tools, LP air jet and water lift/dredge, wet bell diving and
      paramedic training level. Determined by three medical experts, the subcriteria
      for physical fitness were: age, VO2Max, critical flicker fusion frequency (CFFF),
      psychomotor performance, and visual and hearing acuities. The pair-wise
      comparison matrices used to calculate subcriteria weights are filled by the same
      experts. Eight divers were included in the analysis. The AHP yielded scores of
      work experience for seven different project types and a physical fitness score
      for each diver. These scores were used in data envelopment analysis (DEA), to
      obtain an aggregate ranking of the divers. RESULT: The methodology was able to
      differentiate between qualified and unqualified divers. Divers were scored
      between 0 and 1 for each project type. The overall ranking of divers according to
      the average of the seven project types' scores was: 1. Diver 7 (1.0000); 2. Diver
      5 (0.9486); 3, Diver 8 (0.9453); 4. Diver 2 (0.9421); 5. Diver 3 (0.8441); 6.
      Diver 4 (0.7804); 7. Diver 6 (0.6554); 8. Diver 1 (0.3931). DISCUSSION: The
      proposed methodology allows decision-makers to perform evaluations objectively
      and systematically, reducing personal conflicts and confusions resulting from
      subjective immethodical judgments. This methodology is to be applied in real
      projects to validate the selection criteria and confirm the results.

PMID- 25562948
TI  - Protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury
      in a rat model.
AB  - Hyperbaric oxygen therapy is one of the most widely used clinical interventions
      to counteract insufficient pulmonary oxygen delivery in patients with severe lung
      injury. However, prolonged exposure to hyperoxia leads to inflammation and acute
      lung injury. This study aimed to investigate the protective effect of hydrogen
      sulfide on hyperbaric hyperoxia-induced lung injury. Rats were intraperitoneally
      treated with sodium hydrosulphide (NaHS) at 28 MUmol/kg immediately before
      hyperoxia exposure and then exposed to pure oxygen at 2.5 atmospheres absolute
      (atm abs) with continuous ventilation for six hours, Immediately after hyperoxia
      exposure, rats were sacrificed via anesthesia. The bronchoalveolar lavage fluid
      (BALF) was harvested for the detection of protein concentration and IL-1 content,
      and the lungs were collected for HE staining, TUNEL staining and detection of
      wet/dry weight ratio. Our results showed hyperbaric hyperoixa exposure could
      significantly damage the lung (HE staining), increase the protein and IL-13 in
      the BALF, elevate the wet/dry Weight ratio and raise the TUNEL positive cells.
      However, pre-treatment with hydrogen sulfide improved the lung morphology,
      reduced the TUNEL positive cells and attenuated the lung inflammation (reduction
      in IL-13 of BALF and HE staining). Taken together, our findings indicate that
      hydrogen sulfide pretreatment may exert protective effects on hyperbaric
      hyperoxia-induced lung injury.

PMID- 25562949
TI  - Dysbaric osteonecrosis among professional divers: a literature review.
AB  - AIM: Dysbaric osteonecrosis (DON) continues to be a significant occupational
      hazard that has significant medical and social consequences for professional
      divers. This review aims to evaluate the prevalence and risk factors of DON among
      professional divers and to summarize the scientific knowledge regarding
      distribution of the lesions as well as disease prognosis and treatment. METHOD: A
      literature review using the Medline database. RESULTS: The prevalence of DON
      varies between 0 and 70.6% in professional divers, and its prevalence is highest
      in Turkey, Hawaii, Korea and Japan but is dependent on activity and medical
      monitoring. The risk of DON is very low for military divers who strictly obey the
      decompression rules and who undergo periodic medical examination. DON pre-
      dominately occurs in the proximal part of the femur and humerus. In a majority of
      cases, DON will progress despite the absence of further dysbaric exposure.
      CONCLUSION: The pathophysiology of the disease is incompletely understood and
      other etiological factors are perhaps being overlooked.

PMID- 25562950
TI  - Posterior segment changes of the eye during hyperbaric oxygen therapy.
AB  - PURPOSE: To examine central retinal thickness, retinal and vitreo-retinal
      structures, and ocular blood flow during a standard protocol of hyperbaric oxygen
      (HBO2) therapy. METHODS: Retinal thickness and color scans of the vitreo-retinal
      structures were obtained before and after 19 days of HBO2 therapy in 15 patients
      by optical coherence tomography (OCT). Pulsatile ocular blood flow was measured
      by ocular blood flow tonometry. Ocular refraction and axial length of the eye
      were monitored for control. RESULTS: Significant reduction was found in mean
      retinal thickness, -1.7 +/- 1.6 MUm (range -3.9 to 1.1 MUm) (p < 0.001) in nine
      subfields within the 6-mm-diameter circle around the central macula. An
      insignificant decrease in pulsatile ocular blood flow of -19.0 +/- 148.8
      MUl/minute was measured. No morphological changes were seen in retinal and vitreo
      retinal structures. A mean myopic shift of -0.62 +/- 0.39 D (p < 0.001) developed
      while axial length of the eye remained unchanged. CONCLUSIONS: A small decrease
      in central retinal thickness was seen during the study period, but the changes
      were not correlated to the myopic shift. No significant changes in vitreo-retinal
      structures or ocular pulsatile blood flow occurred.

PMID- 25562951
TI  - MRI findings in cervical spinal cord type II neurological decompression sickness:
      a case report.
AB  - Decompression illness affecting the cervical spinal cord is uncommon. We report a
      case that presented with mixed signs and symptoms of cervical myelopathy and Type
      II neurological decompression sickness. This presented a diagnostic dilemma that
      required the use of magnetic resonance imaging (MRI) scan to elucidate the
      underlying cause. Cervical spine MRI revealed the presence of tiny
      hypointensities and edema within the spinal cord that corresponded to the
      clinical findings. The patient recovered with residual neurological deficits
      after hy-perbaric oxygen (HBO2) therapy. To our knowledge, these MRI findings
      have yet to been described in literature and we recommend the use of MRI to
      assist diving physicians in the management of complex cases as long as it does
      not delay recompression.

PMID- 25562952
TI  - More on scuba diving and bleomycin.

PMID- 25562954
TI  - Oxygen toxic seizures during hyperbaric oxygen therapy.

PMID- 25562955
TI  - Response: Oxygen toxic seizures during hyperbaric oxygen therapy.

PMID- 25562956
TI  - [Sequence analysis of the coat protein gene of Chinese soybean mosaic virus
      strain SC7 and comparison with those of SMV strains from the USA].
AB  - To unveil genetic variations between the predominant soybean mosaic virus (SMV)
      strains in China and in the USA, as well as to reveal the potential relevance
      between the similarity of gene sequences and the virulence of the viruses, we
      isolated and sequenced the coat protein (CP) gene of Chinese SMV strain SC7 by RT
      PCR and compared the SC7 sequence with those of SMV strains from the USA.
      Analysis is showed that the CP gene of SC7 was 795 nucleotides in length and
      encoded 265 in amino acids'. The CP gene of SC7 and those of the strains from the
      USA exhibited 4%-5% nucleotide diversity and 1%-2% diversity amino acids. The
      conserved amino-acid sequence associated with aphid spread in the USA strains was
      DAG, and corresponded to DAD in SC7. The virulence of SC7 was greater than that
      of the SMV strains from the USA. Nevertheless, no clear relationships between
      sequence similarity of the CP genes from different strains and their virulence on
      differential hosts were found.

PMID- 25562957
TI  - [The construction of a novel recombinant virus Delta67R-RGV and preliminary
      analyses the function of the 67R gene].
AB  - The Rana grylio virus (RGV) is a member of the genus Ranavirus. It belongs to the
      family Iridoviridae, and contains the gene 67R encoding dUTPase. In order to
      investigate the function of 67R in the replication and infection of RGV, we
      constructed Delta67R-RGV, a recombinant virus with deletion of 67R. First, we
      constructed the plasmid pGL3-67RL-p50-EGFP-67RR which carried an enhanced green
      fluorescence gene (EGFP) as a selectable marker. After homologous recombination
      between pGL3-67RL-p50-EG- FP-67RR and the RGV genome, Epithelioma papulosum
      cyprini (EPC) cells were infected with the resulting mixture. Through ten
      successive rounds of plaque isolation via EGFP selection, all plaques emitted
      green fluorescence, and finally Delta67R-RGV was generated. Total DNA of Delta67R
      RGV infected cells was extracted for PCR analyses. Simulateously, mock infected
      and wild-type RGV (wt-RGV) infected cells were used as a comparison. Results
      showed that 67R could be detected in wt-RGV infected cells, but that only the
      EGFP gene was detected in Delta67R-RGV infected cells. Furthermore, one-step
      growth curves of wt-RGV and Delta67R-RGV were similar. Therefore, 67R and its
      encoding product dUTPase might not be essential for the growth of RGV. These
      results suggest that, homologous recombination and recombinant rana- virus could
      be used to study the gene function of viruses in aquatic animals.

PMID- 25562958
TI  - [Rapid detection of Macrobrachium rosenbergii nodavirus isolated in China by a
      reverse-transcription loop-mediated isothermal amplification assay combined with
      a lateral flow dipstick method].
AB  - White coloration of the muscle of the giant river prawn (Macrobrachium
      rosenbergii) is a serious problem in China. The Macrobrachium rosenbergii
      Nodavirus (MrNV) has been confirmed to be the pathogen that causes this disorder.
      To develop a rapid, sensitive and specific technology for the detection of
      Macrobrachium rosenbergii Nodavirus isolated from China (MrNV-China), a reverse
      transcription loop- mediated isothermal amplification assay combined with a
      lateral flow dipstick (RT-LAMP-LFD) assay method is described. A set of four
      primers and a labeled probe were designed specifically to recognize six distinct
      regions of the MrNV RNA2 gene. Results showed the sensitivity of the RT-LAMP-LFD
      assay was ten-times higher than the reverse-transcription loop-mediated
      isothermal amplification assay (RT-LAMP) with agarose gel electrophoresis. The
      assay was conducted with one-step amplification at 61 degrees C in a single tube
      within 45 min. No product was generated from shrimps infected with other viruses,
      including DNA viruses (infectious hypodermal and hematopoietic necrosis virus
      (IHHNV); white spot syndrome virus (WSSV)) and RNA viruses (Taura syndrome virus
      (TSV); infectious myonecrosis virus (IMNV); yellow head virus (YHV)). Results
      were visualized by the LFD method. Therefore, the described rapid and sensitive
      assay is potentially useful for MrNV detection.

PMID- 25562959
TI  - [Cloning and sequencing analyses of the complete genome of the provirus of the
      Inner-Mongolia pandemic strain of the Jaagsiekte sheep retrovirus].
AB  - To investigate the kinship between the Inner Mongolia pandemic strain and
      representative strains of the Jaagsiekte sheep retrovirus (JSRV), total DNA from
      the lung tissue of a JSRV-infected sheep in Inner Mongolia was used to clone
      fragments of gag, pro and pol genes. The recombinant plasmid pMD-JSRV (including
      complete genomic sequence of the JSRV strain isolated from Inner Mongolia) was
      constructed by linking all the cloned fragments with long terminal repeat (LTR)
      and env gene fragments (cloned previous and reserved by our research team).
      Sequence analyses revealed that the genome was 7690 bp in length and contained
      several typical molecular markers for exogenous form of JSRV. These included the
      Sca I restriction site in the gag gene, two predicted "CCHC" motifs of zinc
      finger in the encoded nucleocapsid protein and the predicted "YXXM" motif in the
      TM region of Env. Homology analyses showed that the virus strain belonged to the
      JSRV type II. pMD-JSRV and AF105220 strains shared a nucleotide identification of
      95%. The full length genomic clone of JSRV could provide a molecular basis for an
      infectious JSRV molecular clone as well as an experimental platform to study the
      detection and pathogenesis of JSRV.

PMID- 25562960
TI  - [Host factor Moloney leukemia virus 10 (MOV10) protein inhibits replication of
      the xenotropic murine leukemia virus-related virus (XMRV)].
AB  - We investigated inhibition of Moloney leukemia virus 10 (MOV10) upon xenotropic
      murine leukemia virus-related virus (XMRV) and made a preliminary study of the
      mechanism of action. Using transfection, infection, western blotting and real
      time polymerase chain reaction, we found that MOV10 inhibited XMRV replication.
      Using MOV10 overexpressed in viral producer cells, MOV10 was shown to reduce the
      infectivity of XMRV. MOV10 could be incorporated into XMRV, suggesting that MOV10
      could undergo encapsidation by XMRV during viral assembly. MOV10 could also
      restrict the DNA production of XMRV in target cells. We found that the putative
      RNA-helicase domain of MOV10 maintained most of its XMRV inhibition. These
      results suggest that MOV10 could be required during the retroviral lifecycle.
      Perturbation of MOV10 disrupts the generation of infectious viral particles,
      suggesting that MOV10 has broad antiretroviral activity. Hence, MOV10 could be
      actively involved in host defense against retroviral infection.

PMID- 25562961
TI  - [Preliminary study of a universal vaccine based on the HA2 protein of the H5N1
      influenza virus].
AB  - Fragments encoding amino acids 76-130 in the linear conserved region (LCR) of
      A/Hubei/1/2010 (H5N1) HA2 was fused to hepatitis B core antigen (HBc) to generate
      a LCR-HBe virus-like particle (VLP). Results showed that the fusion protein of
      LCR-HBc was highly expressed in this prokaryotic expression system. The purified
      LCR-HBc particle stimulated high levels of IgG production in mice with a titer of
      > 1:12 800, and provided 50% cross-protection against lethal challenge by H1N1
      viruses.

PMID- 25562962
TI  - [Adaptive evolution of the hemagglutinin genes of the H6N1 avian influenza virus
      in Taiwan, China].
AB  - In Taiwan, the first human-infecting H6N1 avian influenza virus was isolated in
      2013. To better understand the origin, evolutionary relationship and pathogenesis
      of the H6N1 virus, we studied the adaptive evolution and evolutionary dynamics of
      the hemagglutinin (HA) genes of the H6N1 virus in Taiwan. We felt that such
      studies woud contribute to the further study and control of the virus. Datasets
      were gained from the Flu and Global Initiative on Sharing All Influenza Data
      (GISAID) databases. Then, phylogenetic trees and evolutionary dynamics were
      reconstructed. The evolutionary rate and characterization of adaptive evolution
      were analyzed by bioinformatic methods. Results indicated that the HA genes of
      H6N1 in Taiwan were divided into at least five types, and that the new types that
      the infected human H6N1 belonged to could be local advantage type at present.
      Evolutionary dynamics revealed the viral population expanded first at the end of
      1971, reduced sharply in 2008, and then increased slightly. Three sites were
      identified under positive selection, suggesting that various sites might increase
      the adaptive ability of the virus. Eighty-nine sites were under negative
      selection, revealing that these sites might play an important role in the
      replication and epidemiology of the virus. Interestingly, site 329 upstream from
      the cleavage site was also under negative selection, suggesting that this site
      might be associated with the virulence of H6N1. These data suggest that the HA
      genes of the Taiwanese H6N1 virus have been undergoing adaptive evolution, and
      that an outbreak may occur again. Hence, more attention should be paid to the
      identified sites, to enable timely monitoring and control of a future epidemic.

PMID- 25562963
TI  - [Imported B3 genotype measles viruses were isolated from measles cases in the
      Chinese mainland].
AB  - We isolated and identified the genotypes and molecular characteristics of the
      imported B3 measles virus (MeV) in the Chinese mainland. The Vero/SLAM cell line
      was used to isolate the viruses. Reverse transcription-polymerase chain reaction
      was undertaken to amplify the 450 nucleotide acids of the 3-terminal of the
      nucleoprotein gene. A phylogenetic tree was constructed and similarities in
      homology assessed. Results suggested that the Shanghai isolates MVi/Shanghai.
      CHN/38. 13/02 [B3] and MVi/Shanghai. CHN/40. 13/02[B3] were clustered within the
      same genotype group as the World Health Organization (WHO) B3 genotype reference
      strain. The number of differences in nucleotide acids between the two Shanghai
      isolates was one. The homology of nucleotide acids between the Shanghai isolates
      and the WHO B3 genotype reference strain (MVi/Ibadan. NGA/0.97/1/B3) was 98%.
      Comparative results from the Measles Nucleotide Surveillance system suggested
      that the sequences of Shanghai isolates and the 2013 vi- ruses from Australia,
      Japan, Korea, Hong Kong China, Philippines and Iran were identical. This is the
      first time that the B3 genotype of MeV in the Chinese mainland has been isolated
      since 1993. These data can be used to create a "baseline" of genetic information
      for measles viruses in China, and help to trace the transmission of measles
      viruses in China and the rest of the world.

PMID- 25562964
TI  - [Characterization of the whole genome from a human parechovirus type 3 detected
      from the serum of a child with sepsis in Beijing, China].
AB  - Human parechovirus type 3 (HPeV3) is an important pathogen of severe sepsis.
      HPeV3 is a non- enveloped, single-stranded, positive-sense RNA virus with a
      linear and continuous genomic RNA. The complete genome of a HPeV3 (BJ-C3174)
      strain was analyzed from the serum specimen from a child with sepsis hospitalized
      in Beijing, China, in 2012. The whole genome of BJ-C3174 was 7329 nucleotides
      (nt) in length excluding a poly (A) tail. One large open reading frame (ORF) of
      6531 nt encoding a putative polyprotein precursor of 2177 amino acids (aa) was
      flanked by a 5' untranslated region (UTR) of 709 nt and 3' UTR of 91 nt.
      Phylogenetic analysis showed that BJ-C3174 belonged to HPeV3 and was closest to
      the HPeV3 strain BONN-2 from Germany. Compared with HPeV1-8 reference strains, BJ
      C3174 shared the highest similarities with BONN-2 in full length and in each of
      the gene segments of the genome. The nucleotide and predicted amino acid
      identities of the whole genome between BJ-C3174 and BONN-2 were 99.3% and 99.8%,
      respectively, which were higher than those compared with HPeV3 prototype. Recom-
      bination of the gene segment with other HPeVs types was not identified.

PMID- 25562965
TI  - [Evaluation of a self-prepared anti-WNV-IgG diagnostic ELISA kit with a panel of
      serum samples collected from the people from areas in which West Nile fever is
      endemic].
AB  - In view of that there is no report of west Nile virus infection cases in our
      country, evaluation the self-prepared anti-WNV-IgG diagnostic ELISA kit should be
      employed with the establishment of the serum sample panel collected from the
      entry personnel. All individuals of entry personnel were traveled from epidemic
      area of infectious west Nile disease. In our study, the serum samples were both
      detected by self-prepared anti-WNV-IgG diagnostic ELISA kit and the FDA certified
      kits ,which are FOCUS West Nile Virus IgG Dxselect and Panbio Dengue IgG Capture
      ELISA kits. The self-prepared kit and FDA certified kits were compared and
      assessed simultaneously. Furthermore, the specificity, repeatability and
      stability of the kits were also evaluated. The results indicated that no
      significant difference of detective rates (35. 6% for self-prepared kit vs. 32.5%
      for FOCUS kit, chi2 = 3. 05, P > 0.05) and good consistency (Kappa = 0.8372)
      between the self-prepared kit and FDA certified kits. Also, the positive
      coincidence rate, the negative coincidence rate and the total coincidence rate
      were calculated as 91.18%, 95.34% and 92.66%, respectively. The laboratory self
      developed kit presented similar quality as the counterpart kits with FDA
      certificate. The development of our self-prepared anti-WNV-IgG diagnostic ELISA
      kit will provide technical support for the prevention and control of west Nile
      virus entry.

PMID- 25562966
TI  - [Calcineurin subunit B is not an effective adjuvant when combined with a novel
      HBV protein particle vaccine].
AB  - To compare different adjuvant formulation and explore the impact of Calcineurin B
      subunit(CnB) as adjuvant with a novel HBV protein particle (HBSS1) vaccine in
      mice, female C57BL/6 mice were immunized HBSS1 with Al(OH)3 only, or a normal
      dose (5 MUg) CnB only, or (CnB+ Al(OH)3) mixture as the adjuvant. All immunized
      groups were primed twice at 4-week intervals; followed by boosting with
      recombinant adenoviral based HBV vaccine(rAdSS1) at 10-week intervals. We
      detected the antigen specific humoral response in mice, including total IgG
      antibody and IgG subtyping. Then, we characterized the specific cell-mediated
      immune (CMI) response by detection of gamma-interferon secreting splenocytes
      after stimulaton with S or PreS1 peptide pools. No enhancement of immunity was
      found among the mice with 5 MUg of CnB alone or combined with Al(OH), adjuvanted
      vaccine,which could not induce higher level of anti-PreS1 and anti-S antibodies
      and CMI than that of HBSS1 alone or Al(OH)3 adjuvanted vaccines. We concluded
      that CnB is not an effective adjuvant for a novel HBV subunit vaccine.

PMID- 25562967
TI  - [Temporal fluctuation and genetic characterization of echovirus 11 isolates upon
      surveillance of environmental sewage in Shandong Province, China].
AB  - We wished to analyze the genetic characterization of echovirus 11 (Echo11) from
      samples of environmental sewage in Shandong Province (China). The VP1 coding
      region was typed as the strains were amplified. Phylogenetic analyses on the VP1
      sequences from these isolates, strains isolated from AFP cases in the period 1994
      2010 and others published in GenBank were conducted. From 2011 to 2012, 94 Echo11
      strains were isolated from samples of environmental sewage in Jinan and Linyi
      City in Shandong Province. Numbers of Echo11 were seasonal and reached peaks in
      the summer and autumn in both cities; A- mong these isolates, nucleotide (nt)
      identities were 89.5%-100.0% whereas amino acid (aa) identities were 95.4%
      100.0%. The nt and aa identities were 76.6%-79.7% and 90.4%-92.5% between those
      strains and the prototype (Gregory) strain of Echo11, respectively. All isolates
      from Shandong Province were the A genotype and the strains evolved very rapidly,
      which suggested that several transmission chains was co-circulating. We described
      the temporal fluctuation and genetic characterization of Echo11 isolates from
      surveillance of environmental sewage in Shandong Province, thereby providing
      important information for exploring the dynamic change and genetic variation of
      circulating human enteroviruses in this Province in China.

PMID- 25562969
TI  - [Genetic evidence for recombination and mutation in the emergence of human
      enterovirus 71].
AB  - We wished to understand the genetic recombination and phylogenetic
      characteristics of human en- terovirus A71 (EV-A71) and to explore its potential
      virulence-related sites. Full-length genomes of three EV-A71 strains isolated
      from patients in Chenzhou City (China) were sequenced and analyzed. Possible re-
      combination events and crossover sites were analyzed with Recombination Detection
      Program v4. 1. 6 by comparison with the complete genome sequences of 231 strains
      of EV-A71. Similarly, plot and bootscanning analyses were undertaken with SimPlot
      v3. 5. 1. Phylogenetic trees based on the sequences of VP1 regions were
      constructed with MEGA v5. 2 using the Kimura two-parameter model and neighbor
      joining method. Results suggested that recombination events were detected among
      the three EV-A71 isolates from Chenzhou City. The common main parent sequence was
      from JF799986 isolated from samples in Guang- zhou City (China) in 2009, and the
      minor parent sequence was TW/70516/08. Intertypic recombination e- vents were
      found in the C4b strain (strain SHZH98 isolated in 1998) and C4a strain (Fuyang
      strain isola- ted in 2008) with the prototype strains of CVA4 and CVA14 in the 3D
      region. The chi-square test was used to screen-out potential virulence-related
      sites with nucleotide substitutions of different types of hand, foot, and mouth
      disease (HFMD) cases using SPSS v19.0. Results suggested that there were no
      significant nucleotide substitutions between death cases and severe-HFMD cases.
      Eighteen significant nucleotide substitutions were found between death/severe
      HFMD cases and mild-HFMD cases, and all these 18 substitutions were distributed
      only in P2 and P3 regions. Intertypic recombination among the predominant
      circulating EV-A71 strains in the Chinese mainland and other EV-A strains
      probably dates before 1998, and intratypic recombination might have occurred
      frequently in the HFMD outbreak from 2008 to 2012. Substitutions in the non
      capsid region may be correlated with the changes in virulence of EV-A71. These
      data suggest that researchers should pay more attention to the relationships
      between substitutions in the noncapsid region and the virulence of the virus.

PMID- 25562968
TI  - [Pathogenic spectrum of enteroviruses associated with hand, foot and mouth
      disease by a GeXPTM-based multiplex reverse transcription-PCR assay in Jinan,
      China, 2009-2012].
AB  - We investigated the pathogenic spectrum of enteroviruses associated with hand,
      foot and mouth disease (HFMD) in Jinan, China. A total of 274 specimens with a
      clinical diagnosis of HFMD in Jinan from 2009 to June 2012 were used. A
      GenomeLabTM (GeXP)-based multiplex reverse transcription-polymerase chain
      reaction (RT-PCR) assay was employed to simultaneously detect 15 serotypes of
      human enteroviruses: human enterovirus (EV)71; coxsackievirus A (CVA)16, 4, 5, 6,
      9, and 10; CVB1, 3 and 5; echovirus (Echo) 6, 7, 11, 13 and 19. Results showed
      that all samples were enterovirus-positive, with the most common serotypes being
      EV71 (25.18%) and CVA16 (16.06%), followed by CVA10 (14.23%), CVA6 (7.30%), CVB1
      (1.09%), Echo6 (0.73%), CVA9 (0.36%), CVB3 (0.36%) and co-infections (5.11%).
      CVA10 and CVA6 had the third and fourth highest prevalence of pathogens for HFMD,
      respec- tively. The most prevalent season for CVA10 was from April to August,
      with a peak in April; for CVA6 it was from April to August, with a peak in June.
      This is the first report of the pathogenic spectrum of en- teroviruses associated
      with HFMD in Jinan using the GeXP-based multiplex RT-PCR assay. These data will
      provide the scientific evidence for the prevention and control of epidemics, as
      well as therapy for HFMD patients.

PMID- 25562971
TI  - [Research methods in protein-protein and protein-nucleic acid interactions and
      application in the study of human enterovirus A71].
AB  - Methods for analyses of protein-protein interactions include: yeast two hybrid
      (Y2H), phage dis- play (PD), co-immunoprecipitation (Co-IP), glutathione S
      transferase pull-down (GST pull-down), cellular co-localization, far-western
      blotting, virus overlay protein binding assay (VOPBA), surface plasmon resonance
      (SPR), and fluorescence resonance energy transfer (FRET). Technologies for the
      detection of protein-nucleic acid interactions include: yeast one hybrid (Y1H),
      chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay
      (EMSA), Southwestern blotting, reporter gene, Co-IP, GST pull-down, and PD. These
      methods are often used in the study of the human enterovirus A71 (EV-A71) by our
      research team. Reviews in the Chinese literature in this field are lacking, so we
      reviewed applications of these methods in the study of EV-A71. This review may
      impart important knowledge in the research of other viruses with regard to
      protein-protein and protein-nucleic acid interactions.

PMID- 25562970
TI  - [Current research on picornavirus 3C protease].
AB  - The picornavirus family comprises many small viruses, several of which are
      important pathogens of humans and livestock. The 3C protease (3Cpro) of different
      species and genera of picornavirus contains the classic G-X-C-G motif and Cys-His
      Asp/Glu catalytic triad. 3Cpro conducts maturation cleavage in the regions of VP2
      VP3 and VP3-VP1 in P1, 2A-2B and 2B-2C in P2 and the whole P3. Picornavirus 3Cpro
      has been shown to have significant substrate preference in Q-G/S/A/V/H/R and E
      S/G/R/M as well as species and genera specificity through analyses of the
      maturation cleavage of picornavirus polyproteins. Innate immune adaptors such as
      TRIF, MAVS, IRF3, IRF7 and NEMO have various potential cleavage sites in
      picornavirus 3Cpro (TRIF and NEMO show considerable diversity in their cleavage
      sites). Useful information will be provided for the development of broad-spectrum
      antiviral agents as well as evasion mechanisms of the innate immune system
      against picornavirus 3Cpro through continued research of picornavirus 3Cpro.

PMID- 25562972
TI  - [Research progress in non-primate HCV homologs].
AB  - Infection with the hepatitis C virus (HCV) frequently causes chronic viral
      hepatitis, a major risk factor for the development of cirrhosis and
      hepatocellular carcinoma or primary liver cancer. The origin of the HCV remains
      obscure because no closely related animal virus homolog has been identified.
      Also, efforts to understand the pathogenesis of the HCV have been hampered by the
      absence of small animal models for this human disease. Since 2011, with
      application of new sequencing technologies, various non-primate HCV homologs have
      been identified that will play an important part in understanding the origin and
      evolution of HCV, as well as establishment of related animal models.

PMID- 25562973
TI  - [After giving support to general medical practice on may 22nd, 2014: what will be
      the tendency til 2025?].

PMID- 25562974
TI  - [Knee pain in ambulatory practice].
AB  - Knee pain is a frequent complaint in ambulatory practice. Because of its
      complexity, the knee is prone to trauma, arthritis and the impact of aging.
      Septic arthritis is an emergency and has to be suspected when important knee pain
      is associated with fever, an alteration of the general condition, or in a
      particular social context. In most cases the clinical examination can identify
      the type of pathology. Conservative treatment is beneficial in most cases and
      physiotherapy a major component of the prognosis.

PMID- 25562975
TI  - [Interprofessional pill box management in an ambulatory care setting].
AB  - Complex multimorbid patients are now more common in ambulatory care and the
      management of their medication more frequently needs interprofessional
      collaboration. This qualitative study explored health professional's main
      challenges when introducing, preparing and sharing the use of a pill box for a
      patient. Another objective of this study was to explore options for improving
      care in these situations.

PMID- 25562976
TI  - [Requirements on vision for driving: to see more clearly].
AB  - Primary care physicians have to assess visual functions essential for driving
      when determining medical fitness to drive. However, it can be difficult to apply
      the legal requirements that are described in annex 1 of the ordinance regulating
      the admission to road traffic of 1976 (OAC) due to lack of unambiguousness. This
      article discusses those visual functions that have to be assessed namely visual
      acuity, the visual field and the detection of diplopia and it presents the
      appropriate methods for the primary care setting. Another objective is to discuss
      the relevance of road safety requirements on vision and to present the new Swiss
      requirements proposed for the future in comparison to some international
      recommendations.

PMID- 25562977
TI  - [Patients forgoing health care for economic reasons: how to identify this in a
      primary care setting?].
AB  - Although the performance of the Swiss health system is high, one out of ten
      patients in general practitioner's (GP) office declares having foregone care in
      the previous twelve months for economic reasons. Reasons for foregoing care are
      several and include a lack of knowledge of existing social aids in getting health
      insurance, unavailability of GPs and long waiting lists for various types of
      care. Although long term knowledge of patients or a psychosocial history of
      deprivation or poverty may help identify individuals at risk of foregoing care,
      many may remain undetected. We propose then a few instruments to help GPs to
      identify, in a simple and structured approach, patients at risk of forgoing care
      for economic reasons; these patients are frequently deprived and sometimes poor.

PMID- 25562978
TI  - [Fever and lymphadenopathy: acute toxoplasmosis in an immunocompetent patient].
AB  - Toxoplasmosis is an infectious disease caused by the intracellular parasite
      Toxoplasma gondii. In Switzerland about a third of the population has antibodies
      against this pathogen and has thus already been in contact with the parasite or
      has contracted the disease. Immunocompetent patients are usually asymptomatic (80
      90%) during primary infection. The most common symptom is neck or occipital
      lymphadenopathy. Serology is the diagnostic gold standard in immunocompetent
      individuals. The presence of IgM antibodies is however not sufficient to make a
      definite diagnosis of acute toxoplasmosis. Distinction between acute and chronic
      toxoplasmosis requires additional serological tests (IgG avidity test). If
      required, the most used and probably most effective treatment is the combination
      of pyrimethamine and sulfadiazine, with folinic acid.

PMID- 25562979
TI  - [Cigarette and alcohol advertising in the Swiss free press].
AB  - Tobacco and alcohol are ordinary consumer goods that are still two overriding
      preventable causes of death in Switzerland. Massive advertising supports their
      selling and contributes to maintain a major public health problem up to date. The
      widely read free press represents an interesting advertising mean. The study of
      tobacco and alcohol advertisements published in the free newspaper 20 minutes
      through the year 2012 gives us a good idea of these products' advertising
      strategies. Compared to those for alcohol, the cigarette advertisements are more
      numerous, more suggestive and dealing with emotions. The themes proposed respond
      to young people's expectations in order to incline them to smoke, whereas
      positive images encourage to keep on smoking.

PMID- 25562980
TI  - [Thrombotic thrombocytopenic purpura--an often missed diagnosis].
AB  - Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by
      mechanical anemia with fragmentation of red blood cells and thrombocytopenia by
      consumption. The physiopathology has been extensively studied and a severe
      deficiency of ADAMTS 13, proteolytic enzyme of von Willebrand factor (vWF), has
      been shown to be responsible for its manifestation. We stress the importance of
      visual blood smear examination when clinical and hematological features of TTP
      are present, as it seems to be under-diagnosed, especially in infants and young
      adults. Superpositions with diarrhea-associated hemolytic uremic syndrome (D+
      HUS) and atypical HUS (aHUS) are controversely discussed. Henceforth this article
      proposes a non-exhaustive review of current diagnostic, therapeutic and
      prognostic features of these diseases.

PMID- 25562981
TI  - [Dysmenorrhea: patience, pills or hot-water bottle?].
AB  - Which treatments are used for dysmenorrhea and with what reported outcome? A
      questionnaire was sent to 2400 students and apprentices, following the
      "retrospective treatment-outcome" method. The response rate was 22%. Most
      frequent treatments used are ibuprofene (53%), paracetamol (51%), hormonal
      contraception (40%), hot-water bottle (or hot pad) (35%), food supplements or
      medicinal plants (23%). Physicians only discuss a tiny proportion of dysmenorrhea
      treatment in their consultation, because it is mostly a matter of self-treatment,
      with the family as the source of information in 80% of the cases. Rather
      surprising because not mentioned in most official guidelines, hot-water bottle
      (or hot pad) appears as the treatment followed by the best reported outcome
      (satisfactory in 92% of users).

PMID- 25562982
TI  - [Bad news on antibiotic resistance front].

PMID- 25562983
TI  - [DSM-IV, DSM-V: the lost war of chronic pain patients].

PMID- 25562984
TI  - [Ebola: three experimental clinical trials directed by MSF].

PMID- 25562985
TI  - [Migration and infectious diseases: there are more than Ebola].

PMID- 25562986
TI  - [Lomidine and trisomy 21: stunning awakening of two forgotten scandals].

PMID- 25562987
TI  - [Regional single payer: Geneva proposes to modify federal legislation].

PMID- 25562988
TI  - [Health insurance: no transparency concerning salaries].

PMID- 25562989
TI  - [Self-confidence].

PMID- 25562990
TI  - Streptococcus pseudopneumoniae: prospective detection among community lower
      respiratory isolates in Eastern Saudi Arabia.
AB  - Streptococcus pseudopneumoniae is a distinct pathogen and the available evidence
      suggests its significance in lower respiratory tract infections. The purpose of
      this study is to investigate the occurrence of this new species in patients
      presenting with community-acquired pneumonia in a university hospital setting
      using routine laboratory tests. Sputum samples (n = 213) submitted to the
      microbiology laboratory for culture from cases clinically diagnosed as community
      acquired pneumonia are studied. Optochin variability in ambient air and 5% CO2
      was the criterion used to identify S. pseudopneumoniae. Disc-diffusion and E-test
      on Muller Hinton blood-based agar were used for antibiotic susceptibility testing
      following Clinical Laboratory Standard Institute breakpoints. Out of the screened
      isolates, only six (3%) were identified as S. pseudopneumoniae. None of the
      commercial tests differentiated the pathogens from viridans streptococci so
      diagnostic laboratories need to provide an alternative identification algorithm.
      The six isolates showed susceptibility to penicillin, and five isolates were
      susceptible to vancomycin, but one exhibited low-level resistance (minimum
      inhibitory concentration [MIC]: 1 MUg/mL). All isolates showed high-level
      resistance to macrolides (MIC: 24- > 256 MUg/mL). Although S. pseudopneumoniae
      strains were not sufficiently frequent to justify routine additional incubation
      of sputum samples in ambient air, the high resistance pattern is alarming.
      Further surveillance is needed in diagnostic laboratories to understand the
      epidemiology and clinical significance of the newly described pathogen.

PMID- 25562991
TI  - Factors influencing elevated serum apolipoprotein B48 in diabetic and control
      participants.
AB  - Factors influencing the concentration of apolipoprotein B48 (apo B48) at fasting
      and post-prandial time frames are still being elucidated. This study assesses
      some possible contributing factors including the presence of type 2 diabetes and
      gender using an established enzyme-linked immunosorbent assay (ELISA) method. Apo
      B48 and triglyceride (TG) levels were measured before and for two, four and six
      hours post-prandially in 49 poorly controlled participants with type 2 diabetes
      and in 60 apparently healthy participants (controls). Apo B48 levels in the
      control participants increased post-prandially, peaking at four hours (14.81 +/-
      7.72 MUg/mL) with similar responses demonstrated in TG concentrations. Post
      prandial apo B48 levels were significantly higher in male control participants as
      demonstrated by apo B48 area under the curve (AUC); similar responses were also
      confirmed in triglyceride AUC. Post-prandial apo B48 concentrations in control
      participants correlated with HOMA-IR (P < 0.05). Apo B48 continued to increase
      throughout the six hours in participants with type 2 diabetes (17.73 +/- 13.46
      MUg/mL), when levels were significantly greater than in the control participants
      (13.04 +/- 7.67 MUg/mL) (P < 0.05) despite a decrease in accompanying TG levels
      in participants with type 2 diabetes. Using an ELISA method, this study
      demonstrated that gender, insulin resistance (as evidenced by HOMA-IR) and
      diabetes status influence serum apo B48 levels. These effects were only apparent
      post-prandially.

PMID- 25562992
TI  - Interleukin-6: a possible inflammatory link between vitiligo and type 1 diabetes.
AB  - Vitiligo is a pigmentation disorder of unknown aetiology, but it has been
      reported in association with other autoimmune diseases including type 1 diabetes
      mellitus (T1D). Vitiligo and T1D share a common theory of autoimmunity, but still
      an inflammatory link between them remains to be investigated. This study
      investigates the status and contribution of the inflammatory markers tumour
      necrosis factor-alpha (TNFalpha), interleukin (IL)-6 and IL-1 in patients with
      vitiligo, T1D and vitiligo-associated T1D (Vt-T1D). The data showed that sera
      from Vt-T1D patients (n = 21) had higher levels of TNFalpha, IL-6 and IL-1beta
      compared with vitiligo patients (n = 39), T1D patients (n = 37) or controls (n =
      42). Interestingly, serum levels of IL-6 were found to be significantly higher in
      Vt-T1D patients compared with the levels of TNFalpha and IL-1beta. These data
      also showed that IL-6 was high in Vt patients as compared to the levels of TNFa
      and L-1beta, whereas in T1D patients, IL-6 and TNFalpha were almost the same but
      were higher than IL-1beta. In conclusion, this is the first study to show an
      inflammatory link between vitiligo and T1D. The data conclude that IL-6 plays an
      important role in the pathogenesis of Vt-T1D patients and is likely to gain
      favour as a therapeutic target in these patients.

PMID- 25562993
TI  - Non-vitamin K antagonist oral anticoagulants (NOACs): a view from the laboratory.
AB  - Disadvantages with traditional anticoagulants (vitamin K antagonists and
      heparinoids) have led to the development on non-vitamin K antagonist oral
      anticoagulants (NOACs). These agents are set to replace the traditional
      anticoagulants in situations such as following orthopaedic surgery, in atrial
      fibrillation, and in the prevention and treatment of venous thromboembolism.
      Although superior to vitamin K antagonists and heparinoids in several aspects,
      NOACs retain the ability to cause haemorrhage and, despite claims to the
      contrary, may need monitoring. This review aims to summarise key aspects of the
      NOACs of relevance to the laboratory.

PMID- 25562994
TI  - Nephrotoxic nephritis and glomerulonephritis: animal model versus human disease.
AB  - Glomerulonephritis (GN) encompasses a range of immune-mediated disorders that
      cause inflammation within the glomerulus of the kidney. The pathogenesis of GN is
      complex. Intricacy arises from factors such as autoimmunity, cancer and
      structural abnormalities within the kidney. Studies using animal models have
      highlighted crucial interaction between inflammatory cells and cells intrinsic to
      the kidney, both of which are fundamental to the pathogenesis of GN. This review
      aims to provide insight on a 'suitable' model for nephrotoxic nephritis and
      glomerulonephritis (NTN GN) and relate its experimental validity to humans. The
      BALB/c NTN murine model and Wistar Kyoto (WKY) rat have held experimental
      validity in the study of GN in humans. The chemokine receptor CXCR3 also mediates
      renal T-cell recruitment and subsequent tissue injury in NTN. It is noteworthy to
      consider CXCR3 blockade in Th1-mediated renal inflammation as future therapeutic
      options for patients with GN and subsets thereof. Currently used
      immunosuppressive therapies for GN are not always uniformly effective and are
      frequently associated with serious side-effects. Corticosteroids are effective in
      several types of GN owing to their ability to inhibit the pro-inflammatory
      effects of cytokines known to promote glomerular inflammation. Differences
      between experimental and human GN complicate translation of experimental
      therapies into practice. More research is required to translate animal model
      research into a better comprehension of human GN disease. However, the complexity
      of GN research makes findings a challenge to replicate.

PMID- 25562995
TI  - Cilostazol and blood viscoelasticity in homozygous sickle cell disease.

PMID- 25562996
TI  - Urease production as a marker of virulence in Pseudomonas aeruginosa.

PMID- 25562997
TI  - Helicobacter pylori infection in a Greek cohort with biliary disease.

PMID- 25562998
TI  - [Resuscitation of vital activity after cold arrest of respiration by
      physiological methods without rewarming the body].
AB  - BACKGROUND: The arrest of respiration during deep hypothermia means death, though
      at a low temperature the heart may rhythmically contract for 30-40 minutes more.
      The attempts of rewarming only shorten the time before the heart arrest. Calcium
      ions (Ca2+) are believed to accumulate in the nervous cells in cold. An excess of
      these ions inhibits the metabolism. Moreover it stimulates the cell proteases,
      which destroy the cell membranes. AIM: The aim of the study was to make the the
      attempts to develop the methods of stimulating the respiration and heart without
      rewarming the body. MATERIALS AND METHODS: The work was carried out on wite rats
      250-320g in weight. We introduced disodium salt of ethylenediaminetetraacetic
      acid into the animals. The second method of blocking the mechanisms of the cold
      death was artificial respiration. RESULTS: Ethylenediaminetetraacetic acid reacts
      with calcium ions, decreases their quantity in the blood, and, consequently, in a
      complex manner in the cell protoplasm. Artificial respiration not only increases
      the flow of oxygen into an organism but also decreases the lowest temperature
      threshold of the cold death of an organism. CONCLUSION: A decrease in the
      surviving threshold by 1.5-1.8 degrees C is very important from the point of view
      of reanimation of an organism since to preserve life in the critical period of
      reanimation each 0.5 degrees C are important. Prolongation of minimal frequency
      of heart contractions and maintaining a minimal arterial blood pressure in an
      overcooled organism given the body temperature of 11-12.5 degrees C is a special
      problem of great interest associated with many physiological and biological
      parameters.

PMID- 25562999
TI  - [Neurosis and genetic theory of etiology and pathogenesis of ulcer disease].
AB  - Based on the analysis of literature data and our own research, we have developed
      the original concept of etiology and pathogenesis of peptic ulcer disease. An
      analysis of the literature shows that none of the theories of pathogenesis of
      peptic ulcer disease does not cover the full diversity of the involved functions
      and their shifts, which lead to the development of ulcers in the stomach and the
      duodenum. Our neurogenic-genetic theory of etiology and pathogenesis of gastric
      ulcer and duodenal ulcer very best explains the cause-and-effect relationships in
      the patient peptic ulcer, allowing options for predominance in one or the other
      case factors of neurosis or genetic factors. However, it is clear that the only
      other: combination of neurogenic factor with genetically modified reactivity of
      gastroduodenal system (the presence of the target organ) cause the chronicity of
      the sores. The theory of peptic ulcer disease related to psychosomatic
      pathologies allows us to develop effective schema therapy, including drugs with
      psychocorrective action. On the basis of our theory of the role of Helicobacter
      pylori infection is treated as a pathogenetic factor in the development of peptic
      ulcer disease.

PMID- 25563000
TI  - [Interstitial pacemaker cells].
AB  - This article is devoted to interstitial Cajal cells (syn. telocytes, interstitial
      pacemaker cells, IPC). First those cells were discovered by C.R Cajal in the
      muscle coat of the gut in 1893. Nowadays they have revealed in all parts of
      digestive systems (from esophagus to rectum), urinary and biliary tracts,
      prostate, liver, the walls of arteries and lymphatics, as well Fallopian tube,
      myometrium, mammary glands. Characteristic ultrastructural features are elongated
      spindle shape, length from 40 to 100 MUm, the thickness of 0.2-0.5 MUm, the
      presence of 2-5 processes. Length of them rangingfrom tens to hundreds of
      micrometers, some of them have secondary and tertiary branching, forming a three
      dimensional network. IPC having spontaneous electrical (pacemaker) activity are
      cause to contraction of smooth muscle cells. Depending on the location of IPC
      have different morphological and ultrastructural characteristics. Characteristic
      immunohistochemical markers are CD117, CD34, S100, vimentin. IPC replay to
      acetylcholine, norepinephrine, estrogen, progesterone, and nitric oxide by
      influence ofcorresponding receptors. IPC have specific gap junctions with
      lymphocytes, basophiles, eosinophils, neutrophils, mast cells and dendritic
      cells. Grave pathology of those cells are forming gastrointestinal stromal
      tumors.

PMID- 25563002
TI  - [Immune dysfunction and cognitive deficit in stress and physiological aging. Part
      II: New approaches to cognitive disorder prevention and treatment ].
AB  - Long-term stress as well as physiological aging result in similar immunological
      and hormonal disturbances including hypothalamic-pituitary-adrenal) axis
      depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)
      lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in
      the brain and in the adrenal glands. Since the main mechanisms of inflammation
      control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum
      cytokine levels increase and become sufficient for blood-brain-barrier
      disruption. As a result peripheral cytokines penetrate into the brain where they
      begin to perform new functions. Structural and functional alterations of blood
      brain-barrier as well as stress- (or age-) induced neuroinflammation promote
      influx of bone marrow derived dendritic cells and lymphocyte effectors into the
      brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and
      immune cells having a lot of specific targets alters the brain work that we can
      observe both in humans and in animal experiments. The concept of stressful
      cognitive dysfunction, which is under consideration in this review, allows
      picking out several therapeutic targets: 1) reduction of excessive Treg
      accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory
      reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement
      of blood-brain-barrier function.

PMID- 25563001
TI  - [The impact of immunoactive drugs on passive avoidance response].
AB  - AIM: The objective of this project was to explore the influence of immunoactive
      drugs (tactivin, thymulin, and thymosin fraction 5) on the development of the
      passive avoidance conditioned reflex. MATERIALS AND METHODS: Two types of passive
      avoidance boxes were used--a regular two-chamber box and a modified three-chamber
      box, comprising a dark chamber in which rats were exposed to electrical shock, a
      safe dark chamber, and a light chamber in the center. RESULTS: The project has
      established that the memory trace persists longer under the influence of the
      immunoactive drugs in both models, which is consistent with the reference
      nootropic piracetam test results. Notably, the immunoactive drugs' mnemotropic
      effect was more pronounced in the modified three-chamber box than in the standard
      two-chamber box. Using the modified box helped to establish the influence of
      tactivin, thymulin, and thymosin fraction 5 on the spatial memory component.
      Immunotropic preparations from thymus caused the animals to select the safe
      chamber 24 hours later and in subsequent tests. CONCLUSION: The project's results
      indicate that the drugs tested do possess mnemotropic properties, so their range
      of clinical use can be broadened.

PMID- 25563003
TI  - [Serotype diversity and antimicrobial resistance of Streptococcus pneumoniae].
AB  - The pneumococcus (Streptococcus pneumoniae) is a common bacterial pathogen
      responsible for various infections, especially in children below 5 years of age.
      The severity of pneumococcal infections varies from self-limiting mucosal
      infections, including acute otitis media, sinusitis, and noninvasive pneumonia,
      to life-threatening invasive disease like bacteremia and meningitis. A high
      incidence of pneumococcal infections is combined with a constantly growing
      antibiotic resistance of this pathogen. The growing resistance is thought to be
      associated with misuse of antibiotics and emerging of resistant clones that may
      spread throughout the entire population. Pneumococcal polysaccharide conjugate
      vaccines (PCV) contain an assortment of pneumococcal capsular polysaccharides
      (from 7 to 13) that produce serotype-specific protective antibodies. Since early
      2000's, the introduction of PCV into national immunization programs has been
      shown to substantially decrease the incidence of invasive pneumococcal disease
      and pneumococcal carriage associated with vaccine-type pneumococci in many
      countries. In 2014, PCV vaccination was included in the Russian national calendar
      of prophylactic vaccination. The present article reviews the current literature
      on serotype prevalence, antibiotic susceptibility, and PCV effect on the
      evolution of pneumococcus.

PMID- 25563004
TI  - [Microevolution of cholera agent in the modern period].
AB  - AIM: To carry out comparative molecular genetic analysis of highly pathogenic
      atypical Vibrio cholerae strains biovar El Tor, isolated in the territory of RF,
      in order to determine micro-evolutionary alterations of cholera agent in the
      modern period. MATERIALS AND METHODS: 38 clinical strains have been examined by
      means of polymerase chain reaction, sequencing and MLVA-analysis. The selected
      strains were isolated at different periods of time during cholera epidemic
      complications and differed between each other in virulence. RESULTS: It is
      demonstrated that new variants have emerged in the course of short-term
      microevolution. Their genome structure and function differ from those of all
      previously known strains. The genome alterations have been caused by point
      mutations in ctxB u tcpA genes associated with virulence and located in CTXPhi
      prophage and pathogenicity island VPI-1 respectively, as well as by the extended
      deletion in pandemicity island VSP-II. Presented is the dynamics of genome
      structure and function alterations in modern strains. CONCLUSION: The discovered
      genomic alterations in the new variants of the agent evolved in the process of
      microevolution are indicative of their epidemic potential enhancement and
      probability of virulence potentiation.

PMID- 25563005
TI  - [Palivizumab: four seasons in Russia].
AB  - In 2010, the Russian Federation (RF) registered palivizumab--innovative drug,
      based on monoclonal antibodies for passive immunization of seasonal respiratory
      syncytial virus (RSV) infection in children of disease severe progress risk
      group, which include primarily premature infants, children with bronchopulmonary
      dysplasia and hemodynamically significant congenital heart disease. Currently,
      palivizumab is included in the list of recommended medicines and medical care
      standards of different countries, including Russia. In the review the results of
      Russian research on the progress of RSV infection, its epidemiology and
      immunization experience gained over the 2010-2014 period are summarized in
      relation to the foreign data. During the four epidemic seasons palivizumab
      immunization covered more than 3,200 children of severe RSV infection risk group
      with a progressive annual increase in the number of patients who received the
      drug. Geography of palivizumab immunization is also greatly expanded in our
      country during this time. If during the first two seasons measures of
      immunization were taken mainly in Moscow and St. Petersburg, at the present time,
      thirty one territorial entities of the Russian Federation have the experience in
      the drug application. Analysis of the results of RSV infection immunization (made
      in several regions) confirms the high clinical efficacy and palivizumab safety
      already demonstrated in international studies. In addition, the analysis presents
      the potential to improve the efficiency of the integrated RSV infection
      immunization programs, realizing in the establishment of high-risk child group
      register, adequate counseling for parents, as well as the development of the
      routing of patients and coordination of interaction between different health
      institutions during the immunization.

PMID- 25563008
TI  - [Features of patients with the multiple sensitization diagnostics before allergen
      specific immunotherapy will be set and the assessment of the therapy results with
      the laboratory methods].
AB  - BACKGROUND: Due to the wide expansion of atopy, its early beginning, variety of
      forms, difficulty of specific pathogenetic treatment, and also high cost of in
      vitro researches there is a need of diagnostic test systems development and
      optimization. AIM: To make the assessment of atopy diagnostics efficiency in
      children with a multiple allergy and the analysis of specific immunotherapy
      (ASIT) influence on immune markers level in serum for a choice of the most
      significant predictive indicator. PATIENTS AND METHODS: 457 children (mean age
      8,9 +/- 4,3 years) with pollinosis symptoms that prevalence in spring period were
      tested with birch pollen allergens extract by detecting allergen-specific
      immunoglobulin E (sIgE) levels. Than patient witch showed positive sIgE level
      (243 children) were tested with expanded set of plant allergens (birch, alder,
      hazel, oak pollen, allergens of Rosaceae family and carrot) and set of birch
      pollen allergocomponents (Bet v1, Bet v2, Bet v4, Bet v6). From them 32 patients
      were treated with allergen-specific immunotherapy. Immunological assays were
      performed by indirect immunofluorescent method on ImmunoCAP250 (Sweden). RESULTS:
      It was shown that birch allergens sIgE antibodies detection in patients with
      pollinosis allows to estimate sensitization degree to allergens of related trees
      and could predict their quantitative values. The oak allergens sIgE level is a
      good predictive marker of sIgE level to food plant derived allergens. And apple
      allergens sIgE concentration is closely assotiated with sIgE to fruit allergens
      of Rosacea family. Detection of sensitization to minor allergens in patient
      influences on therapy efficacy prognosis. CONCLUSION: sIgE detection to limited
      number of allergens (birch-oak-apple) is effective to sIgE value assessment in
      patient with allergy to plant causing allergens cross reactivity. Component
      divided in vitro diagnostics directed on reveal of sensitization caused by minor
      allergens, is actual at the answer a question about ASIT validity and its
      efficiency. Component-divided in vitro diagnostics directed on reveal of
      sensitization caused by minor allergens, is actual at the answer a question about
      ASIT validity and its efficiency. Significant results of the therapy are shown
      after double course ASIT that also allows to reduce considerably production of
      sIgE antibodies to significant allergens, and cross reacting plant food
      allergens.

PMID- 25563006
TI  - [Open, non-comparative phase III clinical study to evaluate the efficacy and
      safety of sapropterin in patients with phenylketonuria and
      hyperphenylalaninemia].
AB  - BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive inherited disease
      associated with impaired metabolism of the amino acids phenylalanine (Phe) and
      tyrosine. The main criterion for diagnosis of PKU is high blood Phe level
      determined during neonatal screening. In case where PKU patient is responsive to
      tetrahydrobiopterin treatment, sapropterin restores the impaired activity of the
      enzyme phenylalanine hydroxylase, resulting in the stimulation of normal Phe
      metabolism and thereby enhancing patient tolerance to natural products. AIM: The
      present open, non-comparative clinical study was initiated to assess the degree
      and frequency of response after 8-day sapropterin administration and assess the
      safety of 6-week sapropterin treatment in patients with PKU and
      hyperphenylalaninemia. PATIENTS AND METHODS: The study enrolled 90 patients with
      PKU. The criterion of response to 8-day sapropterin therapy was the reduction of
      Phe blood levels >= 30% compared with the baseline value. RESULTS: Positive
      response to treatment was observed in 30 (33.3%) patients (95% CI 23.7-44.1). The
      mean percentage change in Phe blood levels after the 8-day response test period
      compared to Phe levels prior to dosing was 14.1 +/- 28.4% in the overall subject
      population (95% CI 8.2-20.1) and 44.3 +/- 15.1% in the subpopulation of patients
      with a positive response (95% CI 38.6-49.9). During the study, adverse events
      were reported in 24 (26.7%) patients in the overall population in 16 (53.3%)
      patients in the subpopulation who had a response. CONCLUSION: The study results
      confirmed the efficacy and safety of sapropterin therapy in patients with PKU,
      which is consistent with international clinical trials data.

PMID- 25563007
TI  - [Mitochondrial dysfunction in children with hepatic forms of glycogen storage
      disease].
AB  - AIM: The purpose of the study was to assess mitochondrial dysfunction severity in
      patients with hepatic forms of glycogen storage disease (GSD). PATIENTS AND
      METHODS: We examined 53 children with GSD in the dynamics. Distribution of
      children by disease types was: 1st group--children with GSD type I, 2nd group-
      children with GSD type III, 3rd group--children with GSD type VI and IX;
      comparison group consisted of 34 healthy children. Intracellular dehydrogenases
      activity: succinate dehydrogenase (SDH), glycerol-3-phosphate-dehydrogenase
      (GPDH). nicotinamideadenin-H-dehydrogenase (NADH-D) and lactatdehydrogenase (LDH)
      was measured using the quantitative cytochemical method in the peripheral
      lymphocytes. RESULTS: It was revealed decrease of SDH- (p < 0.001) and GPDH
      activities (p < 0.001), along with increase of the NADH-D activity (p < 0.05) in
      all patients with GSD, (SDH/ NADH-D) index was decreased (p < 0.001). LDH
      activity was increased in groups 1 (p < 0.05) and 3 (p < 0.01), compared with
      comparison group. The most pronounced intracellular enzymes activity deviations
      were observed in children with GSD type I, that correspond to more severe
      clinical form of GSD. It was found strong correlation between intracellular
      enzymes activity and both hepatomegaly level (R = 0.867) and metabolic acidosis
      severity (R = 0.987). CONCLUSION: Our investigation revealed features of
      mitochondrial dysfunction in children with GSD, depending on the GSD type.
      Activities of lymphocytes enzymes correlates with the main disease severity
      parameters and can be used as an additional diagnostic criteria in children with
      hepatic form of GSD.

PMID- 25563009
TI  - [Endogenous intoxication and biochemical protection in children with celiac
      disease: state assesment and correlation-regression analysis].
AB  - AIM: The purpose of the study was to determine the characteristics of endogenous
      intoxication parameters, biochemical protection and reveal their interaction in
      children with celiac disease. MATERIALS AND METHODS: 81 children aged from 1 to
      16 years with celiac disease were examined in acute and remission periods. In
      erythrocytes, blood serum and urine we determined low and moderate molecular
      weight substances (LMMWS), oligopeptides OP); in erythrocytes--the value of
      erythrocyte mechanical hemolysis (MH), malondialdehyde (MDA) content, the
      activity of glutathione reductase GR) and superoxide dismutase (SOD); in blood
      serum--ceruloplasmin (CP) level, alcohol dehydrogenase (ADH) activity; in
      erythrocytes and blood serum--glutathione transferase (GT), and calculated
      intoxication index (II). RESULTS: In children with celiac disease in acute and
      remission periods LMMWS, OP, II levels in blood were statistically significantly
      high, while LMMWS level in urine was low. In both periods MH activity was high (p
      < 0.001), and GSR (p < 0.001) and SOD (p < 0.01) levels were low. We revealed the
      correlation between MDA and II (r = 0.67; p = 0.006), erythrocyte LMMWS and SOD
      (r = -0.61; p = 0.015), erythrocyte LMMWS and ADH (r = 0.62; p = 0.006), between
      GT and OP in urine (r = -0.31; p = 0.026), GTand MDA (r = 0.68; p = 0.000), GT
      and MH (r = -0.46; p = 0.004), between MDA and CP (r = 0.57; p = 0.002) that made
      it possible to develop the models of dependence of the parameters in relation to
      each other. CONCLUSION: In celiac disease there is endogenous intoxication. The
      changes of the first and the second phases of biotransformation, antioxidant
      protection is an essential factor of the disease pathogenesis, since they have an
      effect on endogenous intoxication formation that should be taken into
      consideration in therapy.

PMID- 25563011
TI  - [Gradient of mortality of persons aged 40-59 in regions of the Russian
      Federation].
AB  - AIM: The purpose of the study was to evaluate the differences and factors that
      are interlinked with mortality rates of the population aged 40-59 years in the
      subjects of the Russian Federation. MATERIALS AND METHODS: To calculate mortality
      rates used by Rosstat data on population and number of deaths in the age groups
      40-59 years among men and women in the regions of Russia, as well as indicators
      that characterize the socio-economic condition of the region. RESULTS: In the
      Russian Federation there is a significant mortality gradient between the regions,
      and among male and female population aged 40-59. Except in certain republics of
      the North Caucasus, mortality among male and female population in the other
      regions of the Russian Federation is significantly higher than in Moscow. There
      was a statistically significant correlation of medium strength (r = 0.6; p <
      0.0001) between the mortality rates (both men and women) and indicators such as
      the sale of vodka, liqueurs and brandy (liters per person) per capita of working
      age and older people. Correlation between mortality and indicators reflecting the
      level of life in the regions was weaker or not detected at all. CONCLUSION: For
      an accurate assessment of the factors influencing mortality gradient in regions
      longitudinal cohort studies are needed to be carry out.

PMID- 25563010
TI  - [New approaches in the regulation of blood phagocytes and reduction in the
      formation of oxygen radicals in patients with heart failure].
AB  - AIM: The purpose was to study the effect of actovegin on the formation of
      reactive oxygen species by blood phagocytes of patients with heart failure and on
      SK-N-SH neuron necrosis. MATERIALS AND METHODS: The generation of superoxide
      anion (O2-*) were recorded on whole blood samples (50-100 MUl). Change lucigenin
      dependent hemiluminescence determined on a hemi-luminometer "Biotoks-7". As a
      stimulator of the phagocyte. phorbol ester (PMA, 1 MUm) was used. Necrosis of
      neurons induced by hydrogen peroxide was determined by fluorescence of propidium
      iodit. RESULTS: Blood phagocytes of heart failure patients are initially pre
      activated (primed). These cells spontaneous generated oxygen radicals. Actovegin
      dosa-dependent decreased radicals level and radical induced by PMA (1 MUm). After
      PMA maximal inhibitory effect of actovegin observed in doses higher than 2-3
      mg/ml. The impact of actovegin on the viability of human SK-N-SH neurons in the
      presence hydrogen peroxide (100 MUm) was studied in vitro. Under these conditions
      hydrogen peroxide triggered radical-dependent neurons necrosis Actovegin dosa
      dependent decreased of neuron death. CONCLUSION: Actovegin inhibits spontaneous
      and induced formation of reactive oxygen species generated by blood phagocytes of
      patients with heart failure. Actovegin suppressed necrosis of human SK-N-SH
      neuroblastoma cells caused by hydrogen peroxide. It is assumed that actovegin
      protects_cells of arious organs and tissues, including blood cells and neurons
      that die as a result of ischemia and inflammation by reducing levels of react.ive
      oxygenspecies.

PMID- 25563012
TI  - [Comparative analysis and clinical experience with osteoplastic materials
      materials based on non-demineralized bone collagen and artificial hydroxylapatite
      at the close of bone defects in ambulatory surgical dentistry].
AB  - BACKGROUND: In the presence of bone defects during surgery is not always
      performed osteoptastic material replenishment defect that leads to a lengthening
      of the timing healing, bone regeneration, and treatment outcome. Application of
      osteoplastic materials allows for faster treatment outcomes, accelerate the
      regeneration of bone tissue in the area of the defect. AIM: To examine the
      effectiveness of materials based on non-demineralized bone collagen and
      artificial hydroxylapatite when filling bone defects in outpatient surgical
      practice dentistry. PATIENTS AND METHODS: 22 patients with bone defects of
      various localization using osteoplastic materials were examined and treated. In
      our study, two groups were allocated on the etiology of bone loss: radicular
      cysts and chronic generalized periodontitis. Basic methods of diagnosis and
      monitoring of treatment in the work presented with the cone-beam computed
      tomography and digital orthopantomography. RESULTS: Application of the testing
      osteoplastic materials resulted in faster recovery times with a combination of
      bone defects using resorbable membranes or gel enriched fibrin. In all 22
      patients both tested materials were well tolerated, allergic reactions were not
      identified. However, five patients with a history of endocrinological history,
      during which treatment material is applied on the basis non-demineralized bone
      collagen, the degree of osseointegration has been reduced by 25% compared to the
      somatic healthy patients. In 3 patients with a history of hematological history,
      during which the treatment was applied material on the basis of artificial
      hydroxyapatite, the regeneration of the bone defect was reduced by 20%, which
      suggests the influence of somatic condition of the patient on the regeneration of
      bone tissue. Currently, all patients are on dynamic monitoring, recurrence has
      been detected. CONCLUSION: Materials based on non-demineralized bone collagen and
      hydroxyapatite artificial equally successful during the replacement of the bone
      defect during surgery. However, the degree of regeneration may be different if
      the patient has a history of aggeravated that should be considered when planning
      treatment.

PMID- 25563013
TI  - [Mortality of working age population in Russia and indusrial countries in Europe:
      trends of the last two decades].
AB  - AIM: The purpose of the study was to carry out comparative analysis of the status
      and trends in mortality of male and female population of working age (15-59 (54)
      years) in Russia and the EU-27. MATERIALS AND METHODS: Based on official Russian
      (Rosstat) data, on the global database of the World Health Organization's cause
      of death (The WHO Mortality Database, WHOMD) and databases The Human Mortality
      Database (HMD) of the sex-age composition of the population and the number of
      deaths from certain causes of death by age and sex standardized (direct method)
      mortality rates of working age population from selected causes of death for 1990
      and 2011 in Russia and the average for the EU-27 were calculated. RESULTS:
      Analysis of trends in mortality of male and female population of working age in
      Russia over the past two decades shows that, despite the positive changes in
      during last six years, in 2011, age-standardized mortality rates remained above
      the 1990 level for most causes of death. During the same period in the EU-27
      mortality in men (15-59 years) and women (15-54 years) increased from almost all
      causes ofdeath, which led to an even greatergap between Russia and developed
      countries on this indicator: standardized mortality rate of the male population
      of Russia in 1990 was higher than in the EU-27 by 2.1 times, and by 2011 the gap
      had increased to 3.5 times. The women in the 1990 had 1.5 times higher
      standardized mortality rates, and by 2011 the gap had increased to 2.7 times.
      CONCLUSION: Despite a steady decline in the mortality rates of working age
      population after 2005, its level in 2012 was still higher than the one of 1990
      for both men and women, which led to a further increase in the gap between the
      age-standardized coefficients of mortality rate of working age population in
      Russia and the countries of European Community-27 (15-59 (54)). Faster reduction
      of mortality rate in the working age population will preserve Russian population
      and its labor potential.

PMID- 25563014
TI  - [Fracture healing under intramedullary insertion of wires with hydroxyapatite
      coating].
AB  - AIM: To study morphological features of the bone formation process in
      consolidation of fractures of long tubular bones in conditions of intramedullary
      wires insertion with bioactive calcium-phosphate coating of hydroxyapatite.
      MATERIALS AND METHODS: In experimental study in dogs was simulated open
      comminuted tibia fracture and performed intramedullary insertion of wires with
      hydroxyapatite coating. Using light and electron microscopy, using X-ray electron
      microprobe microanalyses were studied bone regenerates in 14-360 days after
      surgery. RESULTS: It was found that around wires there is a formation of an area
      of active reparative bone formation and angiogenesis, bone shaped case with the
      properties of the conductor and inducer of osteogenesis. Fracture consolidation
      is carried out in the early stages of the primary type without formation of
      cartilage and connective tissue in the bone adhesion. CONCLUSION: Study results
      testify that intramedullary wires with hydroxyapatite coating positively
      influence on the process and intensity of reparative bone formation in fracture
      healing.

PMID- 25563015
TI  - [[Role of dyslipidemia in pathogenesis of vascular events among Arctic Circle
      population].
AB  - Habitation within the polar circle increases cardiovascular mortality rate and
      particularly increases mortality as a result of coronary events. The main reason
      of elevation of mortality from these diseases is a dyslipidemia which developed
      more among alien population residing long time in Far North. Dyslipidemia is less
      found among aboriginal population of Arctic Circle keeping traditional way of
      life and respectively it is low rate of mortality from coronary heart disease.
      The data showed that low rate of dyslipidemia among aboriginal population of
      North regions depends on fish consumption which is high content of Omega3
      polyunsaturated fatty acids.

PMID- 25563016
TI  - [Stimulation of pelvic fracture healing by local injection of autologous plasma
      in combination with metabolically active substances that have an antioxidant and
      antihypoxic effect].
AB  - AIM: The study was aimed at performing an experimental trial of the reparative
      osteogenesis stimulation by local injection of autologous plasma in combination
      with metabolically active substances such as L-ascorbic acid and D-glucose for
      management of pelvic fractures. MATERIAL AND METHODS: The experiment was carried
      out on twenty-six mongrel dog of both sexes aged 1.5 +/- 0.09 years and with body
      weight of 17 +/- 0.5kg. Transverse osteotomy was performed in the acetabulum (n =
      20) and in the ilium body (n = 6). The fractures were stabilized with external
      fixators. On days two through 5 after the operation all dogs had intraarticular
      or intraosseous injections of the saline solution throughout 24 hours in the dose
      of 0.4 ml per day. Experimental animals were additionally injected once a day
      with 1 ml of a composition consisting of the ascorbic acid and glucose. The
      external apparatuses were dismounted on day 21 after the operation. The animals
      for histological study were euthanized on day 14 and 42 after the operation. The
      study used radiographic and histological methods of study as well as the method
      of radiographic electron probe microanalysis. RESULTS: The control animals that
      had either intraosseous or intraarticular saline injections alone had fibro
      cartilaginous union of the pelvic fragments. They developed bone deformity due to
      secondary displacement upon apparatus removal. The experimental animals had
      primary bone union on day 14. The bone was consolidated after the removal of the
      apparatus. CONCLUSION: Autologous blood plasma in combination with active
      substances of ascorbic acid and glucose had a marked stimulating effect on pelvic
      fracture healing if applied locally in the posttraumatic period. The method of
      reparative osteogenesis stimulation that was developed is low traumatic. It does
      not hinder early functional loading and allows control of reparative process
      basing on the biological principles of tissue regeneration.

PMID- 25563017
TI  - [The problems of expertise of biomedical projects and assigning them status of
      breakthrough and world-class].
AB  - There was a sharp increase in the number of scientific fields, research fronts,
      publications and patents in biomedicine in the last five years, which complicates
      the work of the experts on the selection of projects for priority funding. The
      approaches to the identification of perspective directions of research used in
      the world were examined. An attempt was made of formalization of the concepts of
      "breakthrough research" and "world level research" in relation to the Russian
      biomedical projects. The rationale for information support of expert decision
      making about the prospects of development of individual areas of research in
      biomedicine is outlined.

PMID- 25563018
TI  - [Problems of depressive insomnia].
AB  - AIM: To evaluate the efficacy and safety of antidepressant agomelatine in
      relation to the normalization of circadian rhythms in a psychiatric outpatient
      practice. PATIENTS AND METHODS: It was an open label, non-comparative
      observational study of 32 patients 18-55 years during the eight-week therapy of
      major depressive episode mild or moderate severity. For statistical analysis the
      obtained results were used software package Excel 97. RESULTS: On the background
      of treatment marked improvement in levels of depression and decreased intra-group
      scores of the indicators of the scale of Leeds. A statistically significant
      increase in the proportion of responders and remitters is achieved already in the
      first 2 weeks of therapy. CONCLUSION: Thus, in the course of the study, it was
      shown that along with antidepressant effects, agomelatine able to synchronize
      disturbed circadian rhythms and to correct sleep disorders in patients with
      depression.

PMID- 25563019
TI  - [A winning award for the excelling research papers for 2014 on behalf of the
      Israel Medical Association].

PMID- 25563020
TI  - [Self endangerment to save life--competing Jewish legal and moral obligations].
AB  - The obligation to help others often involves personal risk. Consequently, the
      scope and boundaries of this obligation can present a complex dilemma, which has
      practical and moral implications, even in the world of medicine. In Jewish
      medical ethics, the dilemma stems from a confrontation between the duty to help
      others according to the biblical commandment: "Do not stand idly by your fellow's
      blood" on the one hand, and between the right and duty of man to defend himself,
      which is anchored in Jewish law. This article surveys the sources of this
      quandary in Jewish texts throughout the ages such as the Bible, Mishnah, Talmud,
      and responsa literature in various contexts. The discussion highlights the
      essential difference between the formal demands of the law, which protects human
      rights of self-preservation, and the moral requirement to help others even if it
      may include personal risk. The sources suggest distinguishing between various
      levels of risk ranging from high-risk to reasonable or low risk. In this way, the
      classic sources, provide the foundation and the tools for grappling with modern
      contemporary Halachic questions such as organ transplantation, and generate a
      Torah value-based framework to deal with new situations that may arise in the
      future. It is critical to assess the level of risk and the chances for success,
      along with other subjective considerations, in order to ensure the optimal
      ethical course of action.

PMID- 25563021
TI  - [Impact of chronic hepatitis C virus (HCV) on survival of schizophrenic patients
      with co-occurring substance use disorders followed for ten years].
AB  - BACKGROUND: Despite disproportionately high rates of HCV infection among patients
      with schizophrenia and co-occurring substance use disorders, to date, scientific
      evidence for their survival is lacking. AIM: The objective of this study was to
      compare long term survival among this population with and without persisting HCV.
      METHODS: Charts of 212 subjects admitted during a period from January 1, 2002 to
      December 31, 2005 were assessed. Psychiatric diagnoses have been established
      according to international classification of diseases and health related problems
      -10th edition (ICD-10). The Kaplan-Meier survival analysis was used to estimate
      the cumulative survival rates. The association between HCV and mortality was
      estimated using the Cox proportional hazard regression models, with adjustments
      for potential confounders. The main outcome was all-cause mortality. Median
      observation time was 10.0 years. RESULTS: Period prevalence of HCV was 16.0%.
      Total all-cause, unadjusted mortality was 50.0% in populations with HCV versus
      12.9% in populations without HCV (p < .00001, log rank test]. In Cox regression,
      mortality was higher for the population with HCV (adjusted hazard ratio = 2.07;
      95% confidence interval = 1.4-3.0, p < .0001. CONCLUSION: The high mortality of
      schizophrenic dual disorders patients with HCV necessitates new approaches to
      secondary and tertiary prevention to reduce the burden of chronic liver disease
      and to improve survival for those who already have evidence of liver disease. The
      strong adverse effect of HCV on survival should encourage clinical trials
      including schizophrenic patients with dual disorders, to ascertain whether
      patients benefit from treatment choices. It is essential that adequate resources
      and strategies are targeted to the schizophrenic patients with dual disorders
      with HCV.

PMID- 25563022
TI  - [Takotsubo cardiomyopathy following surgical intervention for treatment of bowel
      obstruction].
AB  - We report a case of Takotsubo cardiomyopathy [TCM] occurrence in a 75-years-old
      female after surgical intervention for the treatment of bowel obstruction.
      Approximately 24 hours after the procedure, the hemodynamic and respiratory
      status of the patient deteriorated. Marked ECG ST segment elevation, and troponin
      levels were moderately elevated in a pattern suitable for ST elevation myocardial
      infarction [MI). Coronary angiogram showed no sign of coronary obstruction, and
      an angiography of the left ventricle, presented a template of apical ballooning
      highly suspicious of Takotsubo syndrome.

PMID- 25563023
TI  - [Partial segmental thrombosis of the corpus cavernosum].
AB  - Partial segmental thrombosis of the corpus cavernosum is an unusual clinical
      condition. It is characterized by thrombosis within the proximal segment of the
      corpus cavernosum visualized with radiologic imaging. We report a case of a 56
      year-old man diagnosed with computed tomography, sonography and magnetic
      resonance imaging that revealed a thrombosis in the right proximal corpus
      cavernosum.

PMID- 25563024
TI  - [Blindness and symmetrical neurological deficit in a patient with colon cancer
      receiving adjuvant chemotherapy: is it always cancer?].
AB  - Posterior reversible leukoencephalopathy syndrome [PRES] is characterized by a
      symmetrical brain edema. It is rarely caused by chemotheraphy. While steroids can
      lead to deterioration in the condition of a PRES patient, they are still the drug
      of choice for the more common condition of brain edema secondary to metastases.
      We describe the case of a colon cancer patient who underwent adjuvant treatment
      with capecitabine and oxaliplatin and was admitted to the hospital with seizures
      and brain edema. On admission, the condition was attributed to brain metastases
      and hence a high dose steroid treatment was initiated. Later on, as the patient
      became comatose, the CT was revised and PRES was suggested as an alternative
      diagnosis. After tapering the steroids the patient gradually recovered. This
      report emphasizes the need to be alert and not to confuse PRES with brain
      metastasis in cancer patients.

PMID- 25563025
TI  - [Spiritual support in the spirit of current trends in the Israeli healthcare
      system].
AB  - This editorial is in response to Bar-Sela, Bentur, Schultz and Corn's article
      entitled "Spiritual care in hospitals and other healthcare settings in Israel--a
      profession in the making", published in Harefuah in May 2014. The integration of
      spiritual support into hospitals marks an interesting trend in light of the
      current emphases in the Israeli medical system on technological advancement,
      financial feasibility and quantifiable quality measures. This step is evidence of
      the importance still attached by policy and decisionmakers to those human aspects
      of illness and disease, which are difficult to define and measure. "Spiritual
      Support" is an ancient profession based on the principle, whereby support of the
      spirit is considered a basic human right, in recognition of the spirit as a
      source of strength during times of crisis and distress. This service was
      introduced into the Chaim Sheba Medical Center six years ago for patients with
      untreatable illnesses, and through identification of commonality between their
      coping features and those of rehabilitation patients. It was later expanded into
      the orthopedic and neurological rehabilitation departments. The service is
      provided on an individual level for the patients and in a group formal for their
      caregivers. Spiritual support as an integral part of the multi-disciplinary care
      further ratifies the holistic approach in medical practice, as an everlasting
      value transcending periodical trends. The conclusion drawn is that technological
      advancement, the scientific approach, physical-medical treatment, emotional
      therapy and spiritual support can and should exist side by side to improve the
      welfare and coping abilities of patients dealing with adverse medical conditions.

PMID- 25563026
TI  - [Social anxiety disorder and alcohol use disorders].
AB  - Social anxiety disorder is a mental condition with anxiety and avoidance in
      social settings and is frequently accompanied by self-medication with alcohol.
      Epidemiological studies demonstrate that the risk that patients with social
      anxiety disorder will develop alcohol dependence is more than two-fold. We will
      discuss epidemiological research findings about this comorbidity, as well as
      reasons for the comorbidity and the various treatments available for these
      conditions. Very few studies have analyzed the efficacy of treatments for the
      combination of these disorders and it is not yet clear whether to treat the
      social anxiety disorder first, to treat the alcohol use disorder first or to
      treat both conditions simultaneously. Nevertheless, we propose to treat the
      symptoms of social anxiety disorder and alcohol use disorder in combination with
      the hope of achieving maximal improvement in these patients. Disclosure: I
      received financial assistance from Lundbeck Israel.

PMID- 25563027
TI  - [Emerging new therapies for relapsing remitting multiple sclerosis].
AB  - For the last 20 years the classic treatment for relapsing remitting multiple
      sclerosis was based on injectable disease-modifying drugs, interferon-beta and
      glatiramer acetate (copaxone). Currently, new disease-modifying drugs have been
      added to the clinician's arsenal with similar and even improved efficacy and
      safety profiles. Some of these drugs are given orally and are recommended as
      first line treatment. In this review we will discuss the various innovative and
      emerging disease-modifying drugs including the method of administration,
      mechanism of action, efficacy, safety and major side effects.

PMID- 25563028
TI  - [Carpal tunnel syndrome in pregnancy].
AB  - Pregnancy related carpal tunnel syndrome (PRCTS) is the most frequent
      mononeuropathy during pregnancy. The reported incidence of PRCTS varies widely
      and ranges from 0.8% to 70% depending on the diagnostic method and the physician.
      The etiology for PRCTS is related to hormonal fluctuations, fluid accumulation,
      glucose level fluctuations, median nerve hypersensitivity etc. The diagnosis of
      PRCS is the same as carpal tunnel syndrome (CTS) in the gereral population and
      includes a thorough history, typical symptoms and physical examination.
      Electrodiagnostic studies such as EMG are valuable tools for the ratification of
      the diagnosis of CTS in the general population. But in light of the fact that the
      EMG examination is painful and can cause discomfort to the patient, its routine
      use during pregnancy is controversial and is not required for determining the
      diagnosis. Generally, the syndrome tends to pass after birth, on the other hand,
      according to the literature, it might not pass in lactating women until they stop
      breastfeeding and even afterwards. Treatment of PRCS is mostly conservative, and
      if there is lack of improvement local intracarpal injection of a steroid is
      indicated. Intracarpal injections have demonstrated a significant decrease in
      symptoms and low recurrence in comparison to the general population, and do not
      put the fetus or his mother at risk. A surgical intervention is rarely indicated
      during pregnancy.

PMID- 25563029
TI  - [Cesarean section through history].
AB  - According to historic documents, delivery by abdominal and uterine incision was
      already known to mankind at the beginning of the second millennium BC. This
      delivery method was eventually referred to as "Cesarean Section" because it was
      wrongfully attributed to the way by which Julius Caesar was born. The indications
      for cesarean sections performed in ancient cultures and to the end of the
      medieval period were mainly kings law, that mandated burial of the fetus
      separately from his mother, legal rights regarding inheritance of the father or
      religious motives mandating baptism of the newborn in order to ensure him eternal
      life in heaven. As from the second half of the 19th century AD, and with
      improvement in surgical techniques, as well as in the perioperative environment
      (asepsis, antibiotics, anaesthesia, blood transfusion, etc.), the obstetric
      outcome of cesarean sections was dramaticay improved, both in terms of maternal,
      as well as fetal, outcome. Hence, it became very prevalent throughout the world.
      The emergence of medico-legal medicine and medical ethics issues, have further
      contributed to the use of cesarean sections as the ultimate solution of every
      unusual delivery.

PMID- 25563030
TI  - [Prescribing information for drugs--legal and regulatory implications].
AB  - The regulation of pharmaceuticals is becoming more complex in recent years.
      Current regulation is no longer limited to deciding whether a specific drug would
      be allowed to be placed on the market. Today, a significant part of the
      regulatory process is focused on setting the terms for utilization of each drug,
      regarding the target population, dosages, mode of administration, etc. These
      terms have enormous implications on both pharmaceutical companies and caregivers.
      In Israel, the only publicly available source of information on terms of
      registration is the prescribing information ("physician leaflet"). The
      prescribing information contains instructions for use, as well as a Lot of safety
      information regarding the product. Therefore, the wording of the prescribing
      information may have serious regulatory and legal implications on caregivers. The
      objective of this article is to describe the relevant laws and regulations
      requiring its publication, while discussing the practical issues and implications
      of the use of prescribing information by physicians in Israel.

PMID- 25563032
TI  - Achievement of national clinical practice recommendations among those in the
      Puerto Rican population with diabetes mellitus.
AB  - OBJECTIVE: To analyze glycemic control among patients with diabetes mellitus (DM)
      in Puerto Rico (PR) using the 2011 American Diabetes Association (ADA)
      recommendations and glycemic goals as standards. We also explored other factors
      that are related to glycemic control. METHODS: Glycemic data were obtained from
      600 adults with DM from 5 different regions in PR. The patient's health insurance
      coverage, type of health care provider, type of diabetes treatment, gender, age,
      physical activity, weight, degree of hypertension and degree and type of
      dyslipidemia comorbidities (when one or both were applicable), and disease
      duration were variables of interest. Univariate and bivariate analyses were
      conducted to describe the population and determine the statistical differences in
      the glycemic control of the subjects. RESULTS: Fewer than half of the
      participants achieved the ADA-recommended levels for HbA1c (37.3%) and blood
      pressure (34%). However, relatively more participants met the goals for high
      density lipoprotein cholesterol (51.7%), low-density lipoprotein cholesterol
      (59.9%), and triglycerides (61.5%). The percentage of participants reaching the
      HbA1c, blood pressure, and low-density lipoprotein cholesterol goals at the same
      time was 9.9%. Patients with private health insurance achieved better glycemic
      control than did patients in the public-managed healthcare system. Half of the
      population presented simultaneous hypertension, dyslipidemia, and DM
      comorbidities. Only 50% of the participants were physically active. CONCLUSION:
      In the sample population, glycemic control levels and blood pressure levels in
      adults with DM were far from the ADA-recommended standards. Physical activity
      levels, type of medical insurance, and type of DM medical treatment were the main
      modifiable factors associated with the goal of attaining glycemic control.
      Barriers that limit the achievement of this goal should be analyzed in more
      detail to improve the medical care for people with DM.

PMID- 25563031
TI  - Rapid quantification of resveratrol in mouse plasma by ultra high pressure liquid
      chromatography (UPLC) coupled to tandem mass spectrometry.
AB  - OBJECTIVE: The objective of this study was to develop a rapid and sensitive
      method for the quantification of resveratrol, a polyphenolic compound with
      multiple health beneficial effects, in mouse plasma. METHODS: We used reversed
      phase ultra high pressure-liquid chromatography with tandem mass spectrometry
      detection for the determination of resveratrol levels in mouse plasma. An Agilent
      Zorbax Eclipse Plus C18 column (2.1 mm x 50 mm, 1.8 MUm) was used as the
      stationary phase. The mobile phase consisted of a gradient formed using 1 mM
      ammonium fluoride and methanol. RESULTS: Using this improved method, we obtained
      a retention time of 2.2 min and a total run time of 5 min, for resveratrol. The
      calibration curve for resveratrol showed a linear range from 0.5 to 100 ng/mL.
      The average coefficient of variation was 6% for interday variation and 4% for
      intraday variation. The recovery for resveratrol in mouse plasma was 85 +/- 10%
      (mean +/- standard deviation). CONCLUSION: The method presented herein allows a
      rapid and very sensitive quantification of resveratrol in mouse plasma at
      concentrations as low as 500 ppt.

PMID- 25563034
TI  - Liver transplantation for hepatocellular carcinoma in Puerto Ricans:
      underutilization of a curative therapy.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC), the most common type of liver cancer,
      is becoming a healthcare burden for Puerto Rico and, in particular, for those
      clinics that specialize in liver disease. It is our hypothesis that liver
      transplantation, the most effective curative option for unresectable tumors, is
      underutilized. We describe in detail the outcomes of liver transplants for HCC in
      Puerto Ricans referred to a major liver transplant center in the USA. METHODS:
      Thirty-two Puerto Rican HCC patients receiving transplants (from January 1, 1997,
      through July of 2012) at Tampa General Hospital are described. Recurrence rates
      were calculated, and the Kaplan-Meier estimator was used for survival analysis.
      RESULTS: The proportion of transplants performed for HCC in our Puerto Rican
      patients was only 12% (p = 0.05). Disease-free survival at 1, 3, and 5 years was
      93.7%, 83%, and 78.8%, respectively. Patient survival at 1, 3, and 5 years was
      96.7%, 75%, and 67%, respectively. Sixty-nine percent of the 32 patients were
      alive at the mean follow-up of 56 months. The recurrence rate from 2002 to the
      present is 14%. CONCLUSION: This study provides the most comprehensive report
      detailing the relative benefits of utilizing liver transplantation as a curative
      option for Puerto Ricans with hepatocellular carcinoma. It also incorporates the
      first comprehensive review of the available literature of liver cancer in Puerto
      Rico. Survival and recurrence rates were comparable to published results. In
      Puerto Rico, liver transplantation for HCC patients has been underutilized. In
      order to improve outcomes over the next 2 decades, it is imperative that the
      healthcare system in Puerto Rico handle the burden of this disease using liver
      transplantation, locoregional therapies, and newer treatments for hepatitis C and
      HCC.

PMID- 25563033
TI  - Metabolic syndrome in relation to cardiorespiratory fitness, active and sedentary
      behavior in HIV+ Hispanics with and without lipodystrophy.
AB  - OBJECTIVE: Hispanics in Puerto Rico (PR) have a high prevalence of metabolic
      syndrome (met-syn), partially explained by low physical activity (PA) and
      possibly low cardiorespiratory fitness (VO2peak). Met-syn is also associated with
      lipodystrophy in HIV infected (HIV+) adults taking antiretroviral therapies.
      However, associations between met-syn, VO2peak, PA, sedentary behavior and
      lipodystrophy among HIV+ Hispanics have not been adequately reported. We tested
      the following hypotheses: 1) HIV+ Hispanics with lipodystrophy (HIV-Lipo) would
      have a higher prevalence of met-syn, lower VO2peak and PA, and higher sedentary
      behavior compared with those without lipodystrophy (HIV-no-Lipo) and without HIV
      infection (Non-HIV); and 2) met-syn would be inversely associated with VO2peak
      and PA, and directly associated with sedentary behavior. METHODS: Ninety Hispanic
      adults (32 HIV-Lipo, 28 HIV-no-Lipo, 30 Non-HIV) completed measurements of
      VO2,peak, anthropometry, PA and sedentary behavior with accelerometry, blood
      pressure, fasting glucose, insulin, and lipids. ANOVA and chi-square tests were
      used to detect differences between groups, and regression analyses to test
      associations between variables. RESULTS: More HIV-Lipo (69%) had met-syn compared
      with HIV-no-Lipo (39%) and Non-HIV (37%) (P = 0.002). Sedentary behavior and PA
      were not different, but VO2peak differed between all groups: lowest in HIV-Lipo
      and highest in non-HIV. PA and sedentary behavior were not associated with met
      syn, but PA was directly associated with VO2peak (R2 = 0.26, p < 0.01). Also, a
      lower odds ratio for met-syn was observed with higher VO2peak (0.87; 95% CI: 0.83
      0.95). CONCLUSION: Met-syn is related to lipodystrophy in HIV+ Hispanics in PR,
      and high VO2peak may protect against met-syn in this population.

PMID- 25563036
TI  - The prevalence of Barrett's-esophagus-associated dysplasia in Puerto Rico.
AB  - OBJECTIVE: Barrett's esophagus (BE) is the strongest risk factor of esophageal
      adenocarcinoma (EAC). A previous study found a lower incidence of EAC in Puerto
      Rico (PR) as compared to other racial/ethnic groups in the United States (US).
      Notwithstanding, BE epidemiology in PR is unknown. Study aims: i) to determine BE
      prevalence among individuals with gastroenterological pathology reports from
      three major anatomic pathology laboratories in PR and ii) to describe the
      association between dysplastic BE with age and gender. METHODS: Clinic-based
      study examined data collected from three anatomic pathology laboratories
      encompassing the majority of gastroenterology practices in PR. Individuals with
      histology confirmed BE (January 2007-December 2011) were analyzed (n = 1,232). We
      estimated BE prevalence and adjusted odds ratios (AOR) to assess magnitude of
      association between dysplastic BE with age and gender using logistic regression
      models. RESULTS: Overall BE prevalence was 4.4% (95% CI = 4.1-4.6). Most BE
      patients were males (male-to-female ratio = 2.3:1) with mean age of 64 +/- 13
      years. Ninety one percent of BE biopsies showed no dysplasia whereas 6.2% had
      EAC. BE patients age > 74 years had an increased risk of EAC (AOR: 2.38, 95% CI =
      1.14-4.94) compared to those < 55 years old. Males had increased EAC risk (AOR:
      2.23, 95% CI = 1.23-4.06) compared to females. CONCLUSION: BE prevalence in PR is
      similar to that of non-Hispanic whites and Hispanics in US. The lower occurrence
      of dysplastic BE in PR could explain EAC incidence disparities between PR and
      other groups in the US.

PMID- 25563035
TI  - Demographics, clinical characteristics, IFNL3- and IFNL4- polymorphisms in a
      cohort of hepatitis C patients from Puerto Rico.
AB  - OBJECTIVE: To describe the risk factors for infection, complications, treatment
      received and response in Puerto Ricans with HCV attending gastroenterology
      clinics at UPR-MSC, and the prevalence of single nucleotide polymorphisms (SNPs)
      in IFNL3 and IFNL4 in this population. METHODS: After consent, demographic and
      medical data were obtained and blood samples were drawn from each patient. The
      QIAamp Blood-Maxi Kit was employed for DNA extraction. The TaqMan allelic
      discrimination assay was employed for SNP genotyping. HCV-RNA was measured by
      branched-chain DNA assay. Frequency distributions were used to describe the study
      population and the prevalence of SNPs. The UPR Medical Sciences Campus IRB
      approved the study. RESULTS: Of 259 patients recruited, 64% were men. Genotype
      1was found in 112/136 (82%). Of 150 subjects treated, 19% had sustained
      virological response (SVR), 40% received treatment with pegylated interferon plus
      ribavirin. The SNP frequencies (n = 239) of IFNL3 locus rs12979860 were 27%
      (C/C), 50% (C/T), and 23% (T/T), and for rs8099917 were 46% (T/T), 47% (T/G), and
      7% (G/G). SNP frequencies of IFNL4 locus ss469415590 were 26% (TT/TT), 48%
      (TT/DeltaG), and 26% (DeltaG/DeltaG). CONCLUSION: HCV-infected Hispanics in our
      sample (all of which were Puerto Rican) were shown to have a low SVR rate of 19%.
      The demographic characteristics were similar to those of other study groups in
      the US, except for the annual income. Genotype-1 was the most prevalent in those
      patients with known HCV genotypes. This study group showed significant
      differences with frequencies observed in other populations. Lower frequencies of
      the favorable genotypes were found in our group compared with the populations
      having European and Asian ancestry.

PMID- 25563037
TI  - Oral human papillomavirus infection among drug users in Puerto Rico.
AB  - OBJECTIVE: The prevalence of human papillomavirus (HPV) in the oral cavity has
      not been as well studied as genital infection and its prevalence among drug users
      is uncertain. This study describes the prevalence and correlates of oral HPV
      infection among a sample of drug users in Puerto Rico (PR). METHODS: Cross
      sectional study of 271 drug users aged 18-35 years, not undergoing substance
      abuse treatment, living in the San Juan metropolitan area. Oral samples were
      collected through an oral rinse and HPV infection status was detected through PCR
      and HPV typing. Information on covariates was obtained through face-to-face
      interviews and serum analyses. RESULTS: A total of 34 participants were positive
      for any HPV type (12.5%), whereas 13 individuals (4.8%) were positive for one of
      the 38 type-specific HPV probes evaluated. Among those HPV positive, the most
      common HPV type detected was non-oncogenic HPV 72 (11.8%, n = 4). Oncogenic HPV
      types detected were 35 (5.9%) and 56 (2.9%). Factors associated with oral HPV
      infection included binge drinking (OR = 3.85, 95% CI = 1.40, 10.58), HIV
      positivity (OR = 4.67, 95% CI = 1.58, 13.74) and ever having engaged in
      commercial sex (OR = 3.55, 95% CI = 1.46, 8.67); infection did not differ by age
      or gender. CONCLUSION: Consistent with previous studies in the genital and oral
      tract, HIV infection, alcohol abuse and commercial sex practices were strongly
      associated with oral HPV infection. Future studies should assess the implications
      of oral HPV infection on oral cancer risk in this population.

PMID- 25563038
TI  - A rare case of moyamoya disease in a 20-year-old Puerto Rican female U.S.
      soldier.
AB  - Moyamoya disease is a progressive, occlusive pathology involving the cerebral
      vasculature with particular involvement of the circle of Willis and its
      tributaries. The cause of moyamoya disease is unknown, but is believed to be
      hereditary. Females 20 to 39 years old with moyamoya represent 0.5% of all acute
      cerebral ischemia and infarcts with risk factors including smoking, estrogen
      containing birth control use, coagulopathy, neoplasm, and congenital
      malformation. This case reports on a 20-year-old Puerto Rican female U.S. soldier
      with a 1-year history of migraine headaches with worsening right retro-orbital
      pain, blurred vision, and photophobia. The patient had minimal unilateral
      neurological deficits despite evidence of significant cerebral infarction on non
      contrast computed tomography. Other neuroimaging findings were consistent with
      moyamoya disease with confirmation via cerebral angiography. This case details
      the process of diagnosis and treatment as well as discussing its incidence,
      identification, and treatment options.

PMID- 25563039
TI  - A rare cause of altered mental status and fever in a young military recruit in
      Puerto Rico.
AB  - Heat stroke (HS) is a medical emergency characterized by increased core body
      temperature with associated systemic inflammatory response leading to a syndrome
      of multi-organ damage in which encephalopathy predominates. We describe a case of
      a 29 year old male recruit presenting with altered mental status during military
      training in Puerto Rico. Associated symptoms included high grade fever,
      dizziness, nausea, vomiting, blurred vision and profuse sweating followed by loss
      of consciousness. Upon arrival to medical evaluation the patient was found with
      dry skin and depressed Glasgow Coma Score. Initial laboratories, clinical
      evolution of symptoms and imaging studies were consistent with the diagnosis of
      HS. Patient was managed with mechanical ventilatory support, intravenous fluids
      and external cooling measures. He was later discharged home without any
      neurological sequelae. To our knowledge this is the first documented case of HS
      in Puerto Rico.

PMID- 25563040
TI  - The mysterious HDL.

PMID- 25563041
TI  - Engaging the Caribbean Region for Oral Health.

PMID- 25563042
TI  - To everything, there is a season.

PMID- 25563043
TI  - Although methods may change, member communication will always be a key factor in
      ONS's success.

PMID- 25563045
TI  - Straight from the source. Advisory programs ensure patients' voices are heard in
      cancer care.

PMID- 25563044
TI  - The Case of the cannabis conundrum.

PMID- 25563047
TI  - Cultivating conversations. Improved staff communication results in better
      conversations with patients.

PMID- 25563046
TI  - How do oncology nurse interpreters ensure patients have a voice in their care?

PMID- 25563048
TI  - How do you manage conflict among the cancer care team?

PMID- 25563049
TI  - Let your fingers do the talking. Expressing yourself through blogging.

PMID- 25563050
TI  - How has journaling helped your nursing practice?

PMID- 25563051
TI  - Stress and inflammation combine to fuel cancer growth.

PMID- 25563052
TI  - U.S. Surgeon General reports 5.6 million premature deaths expected from smoking.

PMID- 25563053
TI  - Breast cancer drug appears to extend patients' lives by 15 months.

PMID- 25563054
TI  - A little change may do you good. Switching your practice setting can be the key
      to a rewarding oncology nursing career.

PMID- 25563056
TI  - Estimating range of influence in case of missing spatial data: a simulation study
      on binary data.
AB  - BACKGROUND: The range of influence refers to the average distance between
      locations at which the observed outcome is no longer correlated. In many studies,
      missing data occur and a popular tool for handling missing data is multiple
      imputation. The objective of this study was to investigate how the estimated
      range of influence is affected when 1) the outcome is only observed at some of a
      given set of locations, and 2) multiple imputation is used to impute the outcome
      at the non-observed locations. METHODS: The study was based on the simulation of
      missing outcomes in a complete data set. The range of influence was estimated
      from a logistic regression model with a spatially structured random effect,
      modelled by a Gaussian field. Results were evaluated by comparing estimates
      obtained from complete, missing, and imputed data. RESULTS: In most simulation
      scenarios, the range estimates were consistent with <=25% missing data. In some
      scenarios, however, the range estimate was affected by even a moderate number of
      missing observations. Multiple imputation provided a potential improvement in the
      range estimate with >=50% missing data, but also increased the uncertainty of the
      estimate. CONCLUSIONS: The effect of missing observations on the estimated range
      of influence depended to some extent on the missing data mechanism. In general,
      the overall effect of missing observations was small compared to the uncertainty
      of the range estimate.

PMID- 25563057
TI  - Intelligent modified internal model control for speed control of nonlinear
      uncertain heavy duty vehicles.
AB  - The objective of this paper is to control the speed of heavy duty vehicle (HDV)
      through angular position of throttle valve. Modified internal model control (IMC)
      schemes with fuzzy supervisor as an adaptive tuning are proposed to control the
      speed of HDV. Internal model (IM) plays a key role in design of various IMC
      structures with robust and adaptive features. The motivation to design an IM is
      to produce nearly stable performance as of the system itself. Clustering
      algorithm and Hankel approximation based model order reduction techniques are
      used for the design of suitable IM. The time domain performance specifications
      such as overshoot, settling time, rise time and integral error performance
      indices such as the integral of the absolute error and the integral of the square
      of error are taken into consideration for performance analysis of HDV for various
      uncertainties. 

PMID- 25563058
TI  - Cigarette smoking and emergency care utilization among asthmatic adults in the
      2011 Asthma Call-back Survey.
AB  - OBJECTIVE: Estimate the association between smoking and emergency care in the
      past 12 months among asthmatic adults in a nationally representative sample.
      METHODS: Using the 2011 Asthma Call-Back Survey, the association between smoking
      status and emergency department (ED) and urgent visits among asthmatic adults (n
      = 12 339) was assessed through multivariable logistic regression by a cross
      sectional study design. Analyses used survey weights for US population-based
      estimates. Attributable and population attributable risk were calculated to
      describe the potential benefits of smoking cessation. RESULTS: Adjusting for
      potential confounders, during the past 12 months former smokers had 1.30 (95% CI:
      0.97, 1.74) times the odds and current smokers had 1.46 (95% CI: 1.05, 2.03)
      times the odds of visiting the ED compared to never smokers. Former smokers had
      1.28 (95% CI: 0.99, 1.65) times the odds and current smokers had 1.29 (95% CI:
      0.96, 1.73) times the odds of urgent visits compared to never smokers. Among
      adult asthmatics, an estimated 9% of ED visits and 6% of urgent visits can be
      attributed to current smoking while 7% of ED visits and 7% of urgent visits can
      be attributed to former smoking. CONCLUSIONS: Current and former smokers are more
      likely to need emergency care than never smokers. About 10% of emergency care
      visits among asthmatics can be attributed to smoking assuming smoking is causally
      related to emergency care. Long-term effective management of asthma, particularly
      the prevention and cessation of smoking, could reduce emergency care use and
      health care costs.

PMID- 25563059
TI  - The reliability and utility of spirometry performed on people with asthma in
      community pharmacies.
AB  - OBJECTIVE: To investigate the reliability and the utility of spirometry generated
      by community pharmacists participating in two large asthma intervention trials of
      892 people. METHODS: The Pharmacy Asthma Care Program (PACP) and the Pharmacy
      Asthma Management Service (PAMS) involved up to four visits to the pharmacy over
      6 months for counseling and goal setting. Pharmacists performed spirometry
      according to ATS/ERS guidelines to inform management. The proportion of A-E, F
      quality tests, as per EasyOne QC grades, were recorded. Lung function results
      between visits and for participants referred/not referred to their general
      practitioner on the basis of spirometry were compared. RESULTS: Complete data
      from 2593 spirometry sessions were recorded, 68.5% of spirometry sessions
      achieved three acceptable tests with between-test repeatability of 150 ml or less
      (A or B quality), 96% of spirometry sessions included at least one test that met
      ATS/ERS acceptability criteria. About 39.1% of participants had FEV1/FVC values
      below the lower limit of normal (LNN), indicating a respiratory obstruction. As a
      result of the service, there was a significant increase in FEV1 and FEV1/FVC and
      asthma control. Lung function values were significantly poorer for participants
      referred to their general practitioner, compared with those not referred, on the
      basis of spirometry. CONCLUSIONS: Community pharmacists are able to reliably
      achieve spirometry results meeting ATS/ERS guidelines in people with asthma.
      Significant improvements in airway obstruction were demonstrated with the
      pharmacy services. Pharmacists interpreted lung function results to identify
      airway obstruction for referral, making this a useful technique for review of
      people with asthma in the community.

PMID- 25563060
TI  - Association between vitamin D and respiratory outcomes in Canadian adolescents
      and adults.
AB  - BACKGROUND: Asthma is one of the most prevalent chronic diseases worldwide,
      affecting more than 200 million people. Vitamin D deficiency has been reported
      among individuals with asthma and might play a role in asthma exacerbations. In
      this cross-sectional study, we investigated the association of serum 25-hydroxy
      vitamin D [25(OH)D] levels and current asthma, ever asthma, and lung function.
      METHODS: Data from 3937 subjects aged 13-69 years who participated in the
      Canadian Health Measures Survey - Cycle 1 were considered in this study. Serum
      25(OH)D levels were categorized into <=49 nmol/L (low), 50-74 nmol/L (moderate)
      and >=75 nmol/L (high). RESULTS: The proportion of subjects with current and ever
      asthma was greater in the lower 25(OH)D category than in moderate and high
      categories. After adjusting for potential confounders, subjects in the low
      25(OH)D levels were more likely to have current asthma than those in the moderate
      levels (OR: 1.54, 95% CI: 1.01-2.36). Low 25(OH)D levels were also associated
      with ever asthma (OR: 2.12, 95% CI: 1.40-3.21) among those with a family history
      of asthma and this association was stronger in those with asthma onset before 20
      years of age. High 25(OH)D levels were associated with lower mean value of
      FEV1/FVC ratio. No significant association was observed between 25(OH)D levels
      and other lung function measurements. CONCLUSION: In this study, 25(OH)D levels
      below 50 nmol/L were associated with an increased risk of current and ever
      asthma. Further exploration of this relationship is needed to determine the
      optimal level of vitamin D in the management of asthma in adolescents and adults.

PMID- 25563061
TI  - Reactivity-Structure-Based Rate Estimation Rules for Alkyl Radical H Atom Shift
      and Alkenyl Radical Cycloaddition Reactions.
AB  - Intramolecular H atom shift reactions of alkyl radicals and cycloaddition
      reactions of alkenyl radicals are two important reaction classes in hydrocarbon
      combustion and pyrolysis. In this work, we derive high-pressure rate estimation
      rules that are based on the results of electronic structure calculations at the
      CBS-QB3 level of theory combined with transition state theory calculations. The
      rules for the H atom shift reactions of alkyl radicals cover the 1,2- up to the
      1,7-H shifts. The rules for the cycloaddition reactions of alkenyl radicals are
      for both the endo- and exo-cycloaddition and include the formation of three- to
      seven-member ring products. The results are in good agreement with available
      experiment measurements and other theoretical studies. Both types of reactions
      proceed via cyclic transition state structures. The impact of ring size and
      substituent groups on pre-exponential factors and activation energies are
      discussed in the context of a Benson-type structure-reactivity relationship.
      Similar relationships between the pre-exponential factors and the number of
      internal rotors lost in formation of the transition state are derived for both H
      shift and cycloaddition reactions. The activation energies are found to be more
      complicated. The ring strain contribution to the barrier is much lower for the
      exo-cycloaddition reactions than it is for the other two investigated reaction
      systems. The ring strains for the H-shift and endo-cycloaddition are similar to
      one another and are comparable to that of cycloalkanes for three- to six-member
      rings, but are significantly lower for the larger rings. The results suggest that
      the 1,6-H shift and 1,7-endo-cycloaddition reactions might be faster than
      previous estimates. 

PMID- 25563063
TI  - Pressure Modulation of Backbone Conformation and Intermolecular Distance of
      Conjugated Polymers Toward Understanding the Dynamism of pi-Figuration of their
      Conjugated System.
AB  - Continuous tuning of the backbone conformation and interchain distance of a pi
      conjugated polymer is an essential prerequisite to unveil the inherent electrical
      and optical features of organic electronics. To this end, applying pressure in a
      hydrostatic medium or diamond anvil cell is a facile approach without the need
      for side-chain synthetic engineering. We report the development of high-pressure,
      time-resolved microwave conductivity (HP-TRMC) and evaluation of transient
      photoconductivity in the regioregular poly(3-hexylthiophene) (P3HT) film and its
      bulk heterojunction blend with methanofullerene (PCBM). X-ray diffraction
      experiments under high pressure were performed to detail the pressure dependence
      of pi-stacking and interlamellar distances in P3HT crystallites and PCBM
      aggregates. The HP-TRMC results were further correlated with high-pressure Raman
      spectroscopy and density functional theory calculation. The increased HP-TRMC
      conductivity of P3HT under pressure was found to be relevant to the planarity of
      the backbone conformation and intramolecular hole mobility. The effects of
      pressure on the backbone planarity are estimated to be ~0.3 kJ mol(-1) based on
      the compressibility derived from the X-ray diffraction under high pressure,
      suggesting the high enough energy to cause modulation of the planarity in terms
      of the Landau-de Gennes free energy of isolated P3HT chains as 0.23 kJ mol(-1).
      In contrast, the P3HT:PCBM blend showed a simple decrease in photoconductivity
      irrespective of the identical compressive behavior of P3HT. A mechanistic insight
      into the interplay of intra- and intermolecular mobilities is a key to tailoring
      the dynamic pi-figuration associated with electrical properties, which may lead
      to the use of HP-TRMC for exploring divergent pi-conjugated materials at the
      desired molecular arrangement and conformation. 

PMID- 25563064
TI  - Chelated bis-N-heterocyclic carbene platinum and palladium units as tunable
      components of multinuclear complexes.
AB  - Heterometallic trinuclear M2M' complexes (M = Rh, Ir; M' = Pt, Pd) containing a
      platinum or palladium moiety with chelated bis-N-heterocyclic carbene ligands,
      [(MCp*)2{M'(bisNHC-Cn-R)}(MU3-S)2](BPh4)2 (M = Rh, Ir; M' = Pt, Pd; bisNHC-Cn-R =
      methylene-, ethylene-, or propylene-bridged bis(N-alkyl-imidazolylidene)), were
      synthesized by reacting bis(hydrosulfido)platinum(II) or palladium(II) complexs
      with bisNHC-Cn-R and hydroxo-bridged dinuclear complexes [(MCp*)2(MU-OH)3](BPh4),
      whose dinuclear structures remained intact during the formation of the trinuclear
      complexes, which was confirmed by using electrospray mass spectrometry and NMR
      spectroscopy. The heterometallic trinuclear M2M' complexes with a variety of
      alkylene bridges in bisNHC-Cn-R showed two reversible reduction waves in the
      cyclic voltammogram, and the second reduction potentials were affected by the
      alkylene chain lengths, which caused different dihedral angles between the
      imidazolylidene rings and the coordination plane of the platinum or palladium
      center. The M2M' complexes, except for those containing the platinum unit with
      the ethylene-bridged bisNHC ligands, showed dynamic behavior in solution due to
      the flapping wing motion of the NHC ligand moieties. Although activation
      parameters obtained from line-shape analyses on variable-temperature NMR spectra
      of the complexes suggested that the flapping wing motion occurred without bond
      cleavage, large negative DeltaS(?) values were obtained for the complexes with
      the palladium unit with the ethylene-bridged ligand, suggesting that the Pd
      Ccarbene bond cleavage, accompanied by coordination of solvent molecules,
      occurred. 

PMID- 25563062
TI  - Transparent reporting of a multivariable prediction model for individual
      prognosis or diagnosis (TRIPOD): the TRIPOD Statement.
AB  - Prediction models are developed to aid health care providers in estimating the
      probability or risk that a specific disease or condition is present (diagnostic
      models) or that a specific event will occur in the future (prognostic models), to
      inform their decision making. However, the overwhelming evidence shows that the
      quality of reporting of prediction model studies is poor. Only with full and
      clear reporting of information on all aspects of a prediction model can risk of
      bias and potential usefulness of prediction models be adequately assessed. The
      Transparent Reporting of a multivariable prediction model for Individual
      Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for
      the reporting of studies developing, validating, or updating a prediction model,
      whether for diagnostic or prognostic purposes. This article describes how the
      TRIPOD Statement was developed. An extensive list of items based on a review of
      the literature was created, which was reduced after a Web-based survey and
      revised during a 3-day meeting in June 2011 with methodologists, health care
      professionals, and journal editors. The list was refined during several meetings
      of the steering group and in e-mail discussions with the wider group of TRIPOD
      contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed
      essential for transparent reporting of a prediction model study. The TRIPOD
      Statement aims to improve the transparency of the reporting of a prediction model
      study regardless of the study methods used. The TRIPOD Statement is best used in
      conjunction with the TRIPOD explanation and elaboration document. To aid the
      editorial process and readers of prediction model studies, it is recommended that
      authors include a completed checklist in their submission (also available at
      www.tripod-statement.org).

PMID- 25563065
TI  - High stocking density as a predisposing factor for necrotic enteritis in broiler
      chicks.
AB  - Stocking density is a management factor which has critical implications for the
      poultry industry. The aim of the present study was to investigate the effect of
      high stocking density as a predisposing factor in an experimental model of
      necrotic enteritis in broiler chicks. The experimental challenge model included
      an oral inoculation with 10-fold dose of attenuated anticoccidial vaccine and
      multiple oral inoculations with a specific strain of Clostridium perfringens. Two
      hundred and forty as hatched day-old broiler chicks were randomly allocated to
      four treatment groups according to the following experimental design: group N,
      with normal stocking density (15 birds/m(2)) and no challenge; group D, with high
      stocking density (30 birds/m(2)) and no challenge; group P, with normal stocking
      density and positive challenge; and group DP, with high stocking density and
      positive challenge. From each bird, the intestine, gizzard and liver were
      collected and scored for gross lesions. The intestinal digesta was collected for
      pH and viscosity determination. One caecum from each bird was taken for
      microbiological analysis. The statistical analysis and evaluation of the
      experimental data revealed significant interaction effects between "stocking
      density" and "challenge", regarding gross lesion scores in intestine and liver,
      pH values in jejunum, ileum and caeca as well as C. perfringens counts in the
      caeca (P <= 0.05). High stocking density in challenged birds increased the gross
      lesion score in the intestine (P <= 0.05), contrary to unchallenged birds. It can
      be concluded that high stocking density affects unfavourably the welfare and gut
      health of broiler chicks, predisposes to necrotic enteritis in a subclinical
      experimental model and increases further its importance as a management factor
      for the poultry industry. 

PMID- 25563066
TI  - Relationship between missed care and urinary tract infections in nursing homes.
AB  - The aim of this study was to describe the frequencies and types of missed nursing
      care in nursing homes, and to determine the relationship between missed care and
      the incidence of UTI among nursing home residents. A secondary data analysis was
      conducted including New Jersey nurse survey data and data from Nursing Home
      Compare. The data included responses from 340 direct-care RNs from 63 nursing
      homes. Nearly one half of nurses reported missing at least one necessary care
      activity during their last shift. Of the 12 categories or types of reported
      missed care activities, seven categories of missed care were significantly
      correlated with UTI. Regression analysis indicated that failure to administer
      medications on time and failure to provide adequate patient surveillance
      explained 40% of the variance in the percent of residents with UTI in this
      sample. 

PMID- 25563067
TI  - Entasis through hook-and-loop fastening in a glycoligand with cumulative weak
      forces stabilizing Cu(I).
AB  - The idea of a possible control of metal ion properties by constraining the
      coordination sphere geometry was introduced by Vallee and Williams with the
      concept of entasis, which is frequently postulated to be at stake in
      metallobiomolecules. However, the interactions controlling the geometry at metal
      centers remain often elusive. In this study, the coordination properties toward
      copper ions-Cu(II) or Cu(I)-of a geometrically constrained glycoligand centered
      on a sugar scaffold were compared with those of an analogous ligand built on an
      unconstrained alkyl chain. The sugar-centered ligand was shown to be more
      preorganized for Cu(II) coordination than its open-chain analogue, with an
      unusual additional stabilization of the Cu(I) redox state. This preference for
      Cu(I) was suggested to arise from geometric constraints favoring an optimized
      folding of the glycoligand minimizing steric repulsions. In other words, the
      Cu(I) d(10) species is stabilized by valence shell electron pair repulsion
      (VSEPR). This idea was rationalized by a theoretical noncovalent interactions
      (NCI) analysis. The cumulative effects of weak forces were shown to create an
      efficient buckle as in a hook-and-loop fastener, and fine structural features
      within the glycoligand reduce repulsive interactions for the Cu(I) state. This
      study emphasizes that monosaccharide platforms are appropriate ligand backbones
      for a delicate geometric control at the metal center, with a network of weak
      interactions within the ligand. This structuration availing in glycoligands makes
      them attractive for metallic entasis.

PMID- 25563068
TI  - Patterns of node mapping differ for axial and extremity primary cutaneous
      melanoma: A case for a more selective use of pre-operative imaging.
AB  - PURPOSE: Preoperative lymphoscintigraphy for sentinel lymph node mapping in
      melanoma improves the ability to locate nodes. However, it still remains unclear
      whether this step is required for all patients. METHODS: Patients diagnosed with
      cutaneous melanoma from 1996 to 2012 were identified. Exclusion criteria were in
      situ disease, metastatic disease, or no SLN biopsy. RESULTS: 214 patients were
      evaluated. Median age was 57 years, the majority were male (59.8%), white
      (97.2%), and stage I (60.7%). SLN revealed metastatic disease in 14.5% of
      patients. The most common primary site was the trunk (43.4%) followed by head and
      neck (21%), upper extremity (19.2%), and lower extremity (16.4%). Multiple
      lymphatic basins were most common for head and neck lesions (66.7%) followed by
      those on the trunk (28.8%), with fewer identified when lower (11.4%), and upper
      extremities were involved (4.2%). When comparison was restricted to extremity vs.
      axial, a single basin was noted in 94.5% vs. 59.9% of patients, p < 0.0001. For
      all extremity lesions the SLN was located in the primary basin. Additional sites
      included in-transit (popliteal) and second tier basins. The only melanomas with
      bilateral or contralateral SLN were axial melanomas. CONCLUSIONS: Patients with
      axial melanomas benefit most from lymphoscintigraphy. This step may not be
      required for extremity melanoma.

PMID- 25563069
TI  - Novel polyacetylenes from Coreopsis tinctoria Nutt.
AB  - Phytochemical investigation of the 95% EtOH extract of Coreopsis tinctoria Nutt.
      resulted in the isolation of two novel polyacetylenes, (2S)-(3Z,11E)-decadiene
      5,7,9-triyne-1,2-diol (1) and (2R)-(3E,11Z)-decadiene-5,7,9-triyne-1,2-diol (2),
      together with two known polyacetylenes (3 and 4). The structures of these novel
      compounds were determined by extensive two-dimensional nuclear magnetic
      resonance, high-resolution mass spectrometry, and optical rotation. Compounds 1,
      2, and 4 were evaluated for their anti-proliferative activities against C26 cell
      growth and inhibitory effects on the lipo-poly-saccharides-induced nitric oxide
      production using murine macrophage RAW 264.7 cells. However, compounds 1, 2, and
      4 just showed weak activities. 

PMID- 25563070
TI  - Advanced training for primary care and general practice nurses: enablers and
      outcomes of postgraduate education.
AB  - The aims of the present study were to understand enablers to participation in
      postgraduate education for primary care nurses (PCNs), and to explore how
      postgraduate education has advanced their nursing practice. Cross-sectional
      questionnaires were mailed out in April 2012 to current and past students
      undertaking postgraduate studies in primary care nursing at The University of
      Melbourne, Victoria, Australia. Questionnaires were returned by 100 out of 243
      nurses (response rate 41%). Ninety-one per cent (91/100) of the respondents were
      first registered as nurses in Australia. Fifty-seven per cent were hospital
      trained and 43% were university educated to attain their initial nurse
      qualification. The respondents reported opportunities to expand scope of practice
      (99%; 97/98), improve clinical practice (98%; 97/99), increase work satisfaction
      (93%; 91/98) and increase practice autonomy (92%; 89/97) as factors that most
      influenced participation in postgraduate education in primary care nursing. Major
      enablers for postgraduate studies were scholarship access (75%; 71/95) and access
      to distance education (74%; 72/98). Many respondents reported an increased scope
      of practice (98%; 95/97) and increased job satisfaction (71%; 70/98) as an
      education outcome. Only 29% (28/97) cited an increase in pay-rate as an outcome.
      Of the 73 PCNs currently working in general practice, many anticipated an
      increase in time spent on the preparation of chronic disease management plans
      (63%; 45/72), multidisciplinary care plans (56%; 40/72) and adult health checks
      (56%; 40/72) in the preceding 12 months. Recommendations emerging from findings
      include: (1) increased access to scholarships for nurses undertaking postgraduate
      education in primary care nursing is imperative; (2) alternative modes of course
      delivery need to be embedded in primary care nursing education; (3) the
      development of Australian primary care policy, including policy on funding
      models, needs to more accurately reflect the educational level of PCNs, PCN role
      expansion and the extent of interprofessional collaboration that is evident from
      research undertaken to date. Nurses with postgraduate education have the
      potential to increase their scope of practice, take on a greater teaching role
      and provide more preventive and chronic disease services in primary care.
      Policies aimed at increasing access to education for nurses working in primary
      care would strengthen the primary care nursing profession, and enhance the
      delivery of primary health care services in Australia. 

PMID- 25563071
TI  - Needs Assessment for Incoming PGY-1 Residents in Neurosurgical Residency.
AB  - BACKGROUND: Residents must develop a diverse range of skills in order to practice
      neurosurgery safely and effectively. The purpose of this study was to identify
      the foundational skills required for neurosurgical trainees as they transition
      from medical school to residency. METHODS: Based on the CanMEDS competency
      framework, a web-based survey was distributed to all Canadian academic
      neurosurgical centers, targeting incoming and current PGY-1 neurosurgical
      residents as well as program directors. Using Likert scale and free-text
      responses, respondents rated the importance of various cognitive (e.g. management
      of raised intracranial pressure), technical (e.g. performing a lumbar puncture)
      and behavioral skills (e.g. obtaining informed consent) required for a PGY-1
      neurosurgical resident. RESULTS: Of 52 individuals contacted, 38 responses were
      received. Of these, 10 were from program directors (71%), 11 from current PGY-1
      residents (58%) and 17 from incoming PGY-1 residents (89%). Respondents
      emphasized operative skills such as proper sterile technique and patient
      positioning; clinical skills such as lesion localization and interpreting neuro
      imaging; management skills for common scenarios such as raised intracranial
      pressure and status epilepticus; and technical skills such as lumbar puncture and
      external ventricular drain placement. Free text answers were concordant with the
      Likert scale results. DISCUSSION: We surveyed Canadian neurosurgical program
      directors and PGY-1 residents to identify areas perceived as foundational to
      neurosurgical residency education and training. This information is valuable for
      evaluating the appropriateness of a training program's goals and objectives, as
      well as for generating a national educational curriculum for incoming PGY-1
      residents.

PMID- 25563072
TI  - [Long-term impact of blood pressure and serum glucose control in patients with
      type-2 diabetes mellitus].

PMID- 25563073
TI  - Mental health services in Cambodia, challenges and opportunities in a post
      conflict setting.
AB  - Cambodia had suffered enormously due to war and internecine conflict during the
      latter half of the twentieth century, more so during the Vietnam War. Total
      collapse of education and health systems during the Pol Pot era continues to be a
      challenge for developing the necessary infrastructure and human resources to
      provide basic minimum mental health care which is compounded by the prevailing
      cultural belief and stigma over mental, neurological and substance abuse
      disorders (MNSDs). The mental health research and services in Cambodia had been
      predominantly 'trauma focused', a legacy of war, and there is a need to move
      toward epidemiologically sound public health oriented mental health policy and
      service development. Integrating mental health program with primary health care
      services with specifically stated minimum package of activities at primary level
      and complementary package of activities at secondary level is an opportunity to
      meet the needs and rights of persons with mental, neurological and substance
      abuse disorders (PWMNSDs) in Cambodia, provided there is mental health
      leadership, government commitment and political will. 

PMID- 25563074
TI  - Illness beliefs of Chinese American immigrants with major depressive disorder in
      a primary care setting.
AB  - Underutilization of mental health services in the U.S. is compounded among
      racial/ethnic minorities, especially Chinese Americans. Culturally based illness
      beliefs influence help-seeking behavior and may provide insights into strategies
      for increasing utilization rates among vulnerable populations. This is the first
      large descriptive study of depressed Chinese American immigrant patients' illness
      beliefs using a standardized instrument. 190 depressed Chinese immigrants seeking
      primary care at South Cove Community Health Center completed the Explanatory
      Model Interview Catalogue, which probes different dimensions of illness beliefs:
      chief complaint, labeling of illness, stigma perception, causal attributions, and
      help-seeking patterns. Responses were sorted into categories by independent
      raters and results compared to an earlier study at the same site and using the
      same instrument. Contrary to prior findings that depressed Chinese individuals
      tend to present with primarily somatic symptoms, subjects were more likely to
      report chief complaints and illness labels related to depressed mood than
      physical symptoms. Nearly half reported they would conceal the name of their
      problem from others. Mean stigma levels were significantly higher than in the
      previous study. Most subjects identified psychological stress as the most likely
      cause of their problem. Chinese immigrants' illness beliefs were notable for
      psychological explanations regarding their symptoms, possibly reflecting
      increased acceptance of Western biomedical frameworks, in accordance with recent
      research. However, reported stigma regarding these symptoms also increased. As
      Asian American immigrant populations increasingly accept psychological models of
      depression, stigma may become an increasingly important target for addressing
      disparities in mental health service utilization. 

PMID- 25563075
TI  - Early intensified intravenous cyclosporine therapy predicts favorable response to
      immunosuppressive therapy with rabbit antithymocyte globulin in patients with
      severe aplastic anemia.
AB  - Because of relapse after horse ATG (hATG) therapy, rabbit ATG (rATG) would be a
      realistic alternative as second line immunosuppressive therapy (IST) in severe
      aplastic anemia (SAA) patients. We investigated whether intensified intravenous
      (IV) CsA therapy with rATG would increase the response of IST in SAA patients.
      Sixty-one of the 123 patients received IV CsA therapy with rATG during initial 2
      weeks then changed to oral form (IV CsA group), while other 62 patients just
      received oral CsA therapy with rATG (oral CsA group). Hematologic response rates
      at 3 and 6 months were not different between IV CsA group and oral CsA group
      (p=0.795, p=0.079). However, CsA levels during initial 15 days were higher in
      response-achieved group than response-not-achieved group. Intensive IV CsA group
      maintained CsA level >= 300 ng/ml during 15 days had higher responses at 6 months
      than non-intensive IV CsA group and oral CsA group (p=0.009, p=0.021). Intensive
      IV CsA group (HR=3.239, 95% CI=1.095-8.997, p=0.013) independently predicted
      favorable the hematologic response at 6 months of IST. Early intensified CsA
      therapy was important to achieve favorable outcomes in IST including rATG.

PMID- 25563076
TI  - Distance-based classifiers as potential diagnostic and prediction tools for human
      diseases.
AB  - Typically, gene expression biomarkers are being discovered in course of high
      throughput experiments, for example, RNAseq or microarray profiling. Analytic
      pipelines that extract so-called signatures suffer from the "Dimensionality
      curse": the number of genes expressed exceeds the number of patients we can
      enroll in the study and use to train the discriminator algorithm. Hence, problems
      with the reproducibility of gene signatures are more common than not; when the
      algorithm is executed using a different training set, the resulting diagnostic
      signature may turn out to be completely different. In this paper we propose an
      alternative novel approach which takes into account quantifiable expression
      levels of all genes assayed. In our analysis, the cumulative gene expression
      pattern of an individual patient is represented as a point in the
      multidimensional space formed by all gene expression profiles assayed in given
      system, where the clusters of "normal samples" and "affected samples" and
      defined. The degree of separation of the given sample from the space occupied by
      "normal samples" reflects the drift of the sample away from homeostasis in the
      course of development of the pathophysiological process that underly the disease.
      The outlined approach was validated using the publicly available glioma dataset
      deposited in Rembrandt and associated with survival data. Additionally, the
      applicability of the distance analysis to the classification of non-malignant
      sampled was tested using psoriatic lesions and non-lesional matched controls as a
      model.

PMID- 25563077
TI  - Advances in cell encapsulation technology and its application in drug delivery.
AB  - INTRODUCTION: Cell encapsulation technology has improved enormously since it was
      proposed 50 years ago. The advantages offered over other alternative systems,
      such as the prevention of repetitive drug administration, have triggered the use
      of this technology in multiple therapeutic applications. AREAS COVERED: In this
      article, improvements in cell encapsulation technology and strategies to overcome
      the drawbacks that prevent its use in the clinic have been summarized and
      discussed. Different studies and clinical trials that have been performed in
      several therapeutic applications have also been described. EXPERT OPINION: The
      authors believe that the future translation of this technology from bench to
      bedside requires the optimization of diverse aspects: i) biosafety, controlling
      and monitoring cell viability; ii) biocompatibility, reducing pericapsular
      fibrotic growth and hypoxia suffered by the graft; iii) control over drug
      delivery; iv) and the final scale up. On the other hand, an area that deserves
      more attention is the cryopreservation of encapsulated cells as this will
      facilitate the arrival of these biosystems to the clinic.

PMID- 25563079
TI  - Protection of healthcare staff has to be a priority.

PMID- 25563078
TI  - Analysis of discordant Affymetrix probesets casts serious doubt on idea of
      microarray data reutilization.
AB  - BACKGROUND: Affymetrix microarray technology allows one to investigate expression
      of thousands of genes simultaneously upon a variety of conditions. In a popular
      U133A microarray platform, the expression of 37% of genes is measured by more
      than one probeset. The discordant expression observed for two different probesets
      that match the same gene is a widespread phenomenon which is usually
      underestimated, ignored or disregarded. RESULTS: Here we evaluate the prevalence
      of discordant expression in data collected using Affymetrix HG-U133A microarray
      platform. In U133A, about 30% of genes annotated by two different probesets
      demonstrate a substantial correlation between independently measured expression
      values. To our surprise, sorting the probesets according to the nature of the
      discrepancy in their expression levels allowed the classification of the
      respective genes according to their fundamental functional properties, including
      observed enrichment by tissue-specific transcripts and alternatively spliced
      variants. On another hand, an absence of discrepancies in probesets that
      simultaneously match several different genes allowed us to pinpoint non-expressed
      pseudogenes and gene groups with highly correlated expression patterns.
      Nevertheless, in many cases, the nature of discordant expression of two probesets
      that match the same transcript remains unexplained. It is possible that these
      probesets report differently regulated sets of transcripts, or, in best case
      scenario, two different sets of transcripts that represent the same gene.
      CONCLUSION: The majority of absolute gene expression values collected using
      Affymetrix microarrays may not be suitable for typical interpretative downstream
      analysis.

PMID- 25563080
TI  - School nursing given a boost as 142 new training places announced.

PMID- 25563081
TI  - Increase in nurse training places is only a 'catch up' as demand soars.

PMID- 25563082
TI  - Trust staff vow to claim pay or time in lieu for every hour's overtime worked.

PMID- 25563083
TI  - Campaign against fuel poverty gains support from RCN.

PMID- 25563084
TI  - Peer reviews show importance of research funding.

PMID- 25563085
TI  - Nurse volunteer who contracted Ebola is praised for her bravery.

PMID- 25563086
TI  - RCN warns against overuse of language as a measure of FtP.

PMID- 25563087
TI  - Health advice from obese nurses is often 'ignored'.

PMID- 25563088
TI  - Shift working is bad for you, study finds.

PMID- 25563090
TI  - NHS faces staff exodus if unsocial hours payments are withdrawn.

PMID- 25563091
TI  - Health unions step up pay action with strikes and work to rule.
AB  - Thousands of nurses and midwives across England will stage a 12-hour strike on
      January 29 and a 24-hour walk-out on February 25, marking a significant
      escalation in the pay dispute. 

PMID- 25563093
TI  - Patients campaign to save burger outlet.

PMID- 25563095
TI  - Ready to back justice with action.

PMID- 25563101
TI  - Bronchiolitis.

PMID- 25563102
TI  - The right stuff?
AB  - Health Education England requires universities to introduce values based
      recruitment in the selection of applicants to nursing courses. The approach is
      intended to ensure that only individuals with the right values train to be
      nurses. Critics say there is no evidence that recent graduates' values contribute
      to poor care.

PMID- 25563103
TI  - By reaching out we can change worlds.
AB  - The Ebola epidemic has forced many nurses to face the limits of their power to
      help. But our feelings of empathy can be used to spark more local engagement with
      the people we help.

PMID- 25563104
TI  - Support after transplant.
AB  - Blood cancer charity Anthony Nolan has funded a post-transplant specialist nurse
      role to support blood cancer patients throughout the long journey to recovery.
      The first nurse to take on the role, Hayley Leonard, works with patients to
      achieve the best possible quality of life after transplant.

PMID- 25563119
TI  - Please continue to support our work in Africa to combat HIV/AIDS.

PMID- 25563120
TI  - European nurses lose out in terms of registration and skills.

PMID- 25563121
TI  - Ebola shines a spotlight on the vital role of front line healthcare workers.

PMID- 25563122
TI  - How is the RCN going to support members in claiming overtime?

PMID- 25563124
TI  - 'Florence' is being developed as a digital healthcare assistant.

PMID- 25563125
TI  - The role of chaplaincy services in today's multicultural NHS.

PMID- 25563126
TI  - Preventing central venous catheter-related bloodstream infection.
AB  - Nurses should be able to apply evidence-based practice in a way that is
      appropriate for the individual patient. This article discusses one area, the
      incidence of central venous catheter-related bloodstream infection in acute care,
      to examine the available evidence and identify ways in which this evidence can be
      applied to practice. Research indicates that implementing best practice at the
      time of insertion is a principal determinant in minimising the risk of catheter
      related bloodstream infection. 

PMID- 25563127
TI  - Improving oral hygiene for patients.
AB  - Systematic reviews and patient safety initiatives recommend that oral hygiene
      should be part of routine patient care. However, evidence suggests it is often
      neglected in hospitals and care homes. Research recommends encouraging beliefs
      that support oral hygiene, and teaching nurses appropriate skills, as necessary
      prerequisites to implementing best practice in hospital wards. This article
      describes a pilot study of an educational workshop on oral hygiene. Results from
      the pilot study suggest that this workshop is a feasible intervention for a
      service-wide trial. The literature suggests that other interventions are required
      to complement this approach if nurses are to make oral hygiene a priority in
      daily patient care. 

PMID- 25563128
TI  - Writing up research for publication.
AB  - This article describes the process of preparing a research article for
      publication in a nursing journal. It is aimed at nurses who wish to share their
      research results with other health professionals and is designed to help the
      researcher who is new to publishing. In writing a research article, the author
      describes what he or she has learned. This may enable others to replicate or
      develop the research, or improve their clinical practice. Published research
      should represent the research clearly and accurately, present the findings or
      results, and provide reasoned conclusions about what has been discovered. 

PMID- 25563130
TI  - The patient champion.

PMID- 25563129
TI  - Breaking bad news.

PMID- 25563132
TI  - New approach to intervention.

PMID- 25563134
TI  - Student life - 'The best nurse I can be'.

PMID- 25563135
TI  - Identification of insecticidal constituents of the essential oils of Dahlia
      pinnata Cav. against Sitophilus zeamais and Sitophilus oryzae.
AB  - The aim of this research was to determine the chemical composition of the
      essential oils of Dahlia pinnata, their insecticidal activity against Sitophilus
      zeamais and Sitophilusoryzae and to isolate insecticidal constituents. Based on
      bioactivity-guided fractionation, active constituents were isolated and
      identified as D-limonene, 4-terpineol and alpha-terpineol. Essential oils and
      active compounds tested exhibited contact toxicity, with LD50 values ranging from
      132.48 to 828.79 MUg/cm(2) against S. zeamais and S. oryzae. Essential oils
      possessed fumigant toxicity against S. zeamais and S. oryzae with LC50 from 14.10
      to 73.46 mg/L. d-Limonene (LC50 = 4.55 and 7.92 mg/L) showed stronger fumigant
      toxicity against target insects. 4-Terpineol (88 +/- 8%) and d-limonene (87 +/-
      5%) showed the strongest repellency against S. zeamais and S. oryzae,
      respectively. The results indicate that essential oils and insecticidal
      constituents have potential for development into natural fumigants, insecticides
      or repellents for control of the stored-product insect pests.

PMID- 25563136
TI  - Moyamoya syndrome in a patient with Noonan-like syndrome with loose anagen hair.
AB  - BACKGROUND: Noonan-like syndrome with loose anagen hair is one of the RASopathies
      characterized by Noonan syndrome-like features with unique ectodermal
      abnormalities. This syndrome is caused by mutations in the SHOC2 gene. We
      encountered a patient with moyamoya syndrome associated with Noonan-like syndrome
      with loose anagen hair presenting with transient ischemic attacks. PATIENT
      DESCRIPTION: A 6-year-old girl was diagnosed with Noonan-like syndrome with loose
      anagen hair because of profound short stature and ectodermal anomalies such as
      sparse and easily pluckable hair. A heterozygous mutation of c.4A>G (p.S2G) in
      the SHOC2 gene was identified, and recombinant human growth hormone therapy was
      initiated at 8 years of age. At age 10, she manifested recurrent left hemiplegia.
      Moreover, cerebrovascular imaging revealed occlusion or narrowing of both
      internal carotid arteries and both middle cerebral arteries with distal moyamoya
      like vessels. She is treated with aspirin and calcium channel blocker.
      CONCLUSIONS: We describe the first case of Noonan-like syndrome with loose anagen
      hair associated with moyamoya syndrome, although it has been reported to be
      associated with a few cases of other RASopathies, including Noonan,
      cardiofaciocutaneous, and Costello syndromes. This report emphasizes the
      associations between cerebrovascular anomalies and Noonan-like syndrome with
      loose anagen hair.

PMID- 25563137
TI  - Evaluation of factors affecting tumor response and survival in patients with
      primary and metastatic liver cancer treated with microspheres.
AB  - OBJECTIVE: Radioembolization with the yttrium-90 (Y-90) microspheres is being
      used increasingly more often in the treatment of patients with primary or
      metastatic liver cancer. Although technetium-99m macroaggregated albumin (Tc-99m
      MAA) scintigraphy performed following diagnostic angiography has an important
      role in predicting the effectiveness of treatment and in dose estimation, the
      number of studies using quantitative assessment of Tc-99m MAA scintigraphy is
      limited in this field. In the present study, the aim was to assess whether a
      tumor dose is required to obtain objective tumor response and to check whether
      this threshold value is predictive in terms of tumor response, survival, and
      liver toxicity by using Tc-99m MAA single-photon emission computed tomography
      (SPECT) images. MATERIALS AND METHODS: Overall, 54 patients (20 women and 34 men;
      median age: 60 years) who underwent Y-90 Resin (SIR-Spheres) and Glass
      (TheraSphere) microsphere treatment with a diagnosis of unresectable liver cancer
      between August 2010 and April 2013 were included in the study. The mean doses to
      normal liver and tumor were estimated for each patient using Tc-99m MAA SPECT
      images and the medical internal radiation dosimetry method. The responses were
      assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) and
      European Organisation for Research and Treatment of Cancer (EORTC) criteria.
      Kaplan-Meier survival curves and univariate Cox regression analysis were used in
      survival analysis. The relationship between treatment response and other
      parameters included was assessed using logistic regression analysis. The
      variables with a P value less than 0.01 in univariate analysis were assessed with
      multivariate analysis. RESULTS: Fifty-four Y-90 microsphere treatments (eight by
      using a Y-90 glass microsphere and 46 by using a Y-90 resin microsphere) were
      performed. In the multivariate analysis, the only parameter related to response
      was tumor dose (P<0.01). With a tumor dose of 280 Gy or higher, objective tumor
      response was observed in 59 and 77% of the patients according to RECIST and EORTC
      criteria, respectively, and the tumor control rate was found to be 95% according
      to both criteria. In addition, it was found that only tumor dose was correlated
      with progression-free survival (PFS) (P<0.001) and overall survival (OS)
      (P=0.018). When the tumor dose was 280 Gy or higher, median PFS increased from 2
      to 10.7 months (P<0.001), whereas median OS increased from 9 to 17.6 months
      (P=0.018). However, reversible >= G2 liver toxicity was observed in 3.7% (2/54)
      of the patients within 3 months after radioembolization with a median normal
      liver dose of 40 Gy (10-102 Gy). There was reversible >= G3 liver toxicity in
      3.7% (2/54) of patients, but no G4 liver toxicity was observed. Clinical
      radiation hepatitis and treatment-induced liver failure were not observed in any
      of these patients. CONCLUSION: Tc-99m MAA SPECT has a predictive value in terms
      of response to radioembolization, PFS, and OS. Dosimetry based on Tc-99m MAA
      SPECT images can be used in the selection of patients and, in particular, to
      adaptation of treatment plan in selected patients.

PMID- 25563138
TI  - A new model combining the liver/spleen volume ratio and classification of varices
      predicts HVPG in hepatitis B patients with cirrhosis.
AB  - BACKGROUND: Although the therapy of varices in liver cirrhosis has improved, the
      mortality during a variceal hemorrhage episode remains high. Patients with
      hepatic venous pressure gradient (HVPG) greater than 12 mmHg have been identified
      as being at a higher risk for the first hemorrhage episode. AIMS: The aim of this
      study was to find an accurate method to predict HVPG greater than 12 mmHg.
      METHODS: A total of 150 hepatitis B patients with liver cirrhosis were enrolled
      and analyzed retrospectively. The patients were randomly divided into the
      experiment group and the validation group. The experiment group was used to
      construct a model to predict HVPG greater than 12 mmHg. The validation group was
      used to verify the predictive equation. RESULTS: The predictive model combined
      with the liver/spleen volume ratio and classification of varices was constructed
      to predict HVPG greater than 12 mmHg. The area under the curve of this predictive
      equation was 0.919. The values of sensitivity, specificity, positive predictive
      value, and negative predictive value were 92.9, 87.0, 89.7, and 90.9%,
      respectively. The following equation was used to calculate the HVPG score: HVPG
      score = 13.651 - 6.187*ln (liver/spleen volume)+2.755*[classification of varices
      score (classification of varices : small, 1; large; 2]. CONCLUSION: The new model
      combining the liver/spleen volume ratio and classification of varices can
      accurately predict HVPG in hepatitis B patients with cirrhosis.

PMID- 25563139
TI  - Inflammatory bowel disease among Bedouin Arabs in southern Israel: urbanization
      and increasing prevalence rates.
AB  - BACKGROUND AND AIM: Inflammatory bowel disease (IBD) has been associated with
      genetic and environmental factors, including urban living. IBD was rare in the
      Israeli Bedouin community 30 years ago. Over recent decades, a large proportion
      of this community has undergone a transition from a nomadic to a western
      lifestyle. Our aim was to carry out an updated evaluation of the clinical and
      epidemiological features of IBD in the Bedouin sector of southern Israel.
      METHODS: All Bedouin patients with a known diagnosis of Crohn's disease (CD) or
      ulcerative colitis (UC) were included in the retrospective study. RESULTS: The
      cohort included 31 CD patients and 31 UC patients. The mean age of the patients
      at diagnosis was 29+/-10.9 and 35+/-17.5 years for CD and UC, respectively. The
      prevalence rate for CD was 15.5/100,000 and the incidence rate was 0.8
      3.55/100,000. Fourteen of the CD patients (45%) had ileal disease and 64.5% had
      inflammatory disease behavior according to the Montreal classification. Eleven of
      the CD patients (35%) were treated with anti-TNF-alpha and 26% had undergone
      surgery. Over the previous decade, the prevalence of UC was 14/100,000 and the
      incidence was 0.5-2.39/100,000. Eighteen UC patients (58%) had left-sided
      colitis. Three (9.7%) had undergone total colectomy for severe disease.
      CONCLUSION: We found an increased prevalence of IBD in the Bedouin population,
      associated with their change in lifestyle over previous decades. However, the
      prevalence is still markedly lower than that in other population groups. A high
      percentage of patients were treated with anti-TNF-alpha and/or surgery.

PMID- 25563140
TI  - Retrograde detection of the intrahepatic portal vein in primary biliary
      cirrhosis: is sinusoidal blockage the underlying pathophysiology?
AB  - OBJECTIVE: The aim of this study was to explore the underlying pathophysiological
      mechanism for portal hypertension in primary biliary cirrhosis (PBC) using
      radiological findings. PATIENTS AND METHODS: The study included 10 patients with
      PBC (Scheuer stage I, one patient; stage II, two patients; and cirrhosis, seven
      patients) and 29 patients with viral cirrhosis. Both groups underwent Doppler
      ultrasound and hepatic venous catheterization. The Doppler data, pressure data,
      and vascular enhancement findings were compared between the groups. RESULTS:
      Hemodynamics in the portal trunk and hepatic vein upon Doppler sonography did not
      differ between patients with viral cirrhosis, cirrhotic PBC, and noncirrhotic
      PBC. The hepatic venous pressure gradient (mean+/-SD) was 225.5+/-77.1 mmH2O
      (range 125-445 mmH2O) in viral cirrhosis, 224.6+/-39.5 mmH2O (range 170-262
      mmH2O) in cirrhotic PBC, and 41.3+/-7.4 mmH2O (range 33-47 mmH2O) in noncirrhotic
      PBC, being significantly higher in viral cirrhosis and cirrhotic PBC than
      noncirrhotic PBC (P=0.0005). The intrahepatic portal vein was detected in a
      retrograde manner on the hepatic venogram in 29/29 (100%) patients with viral
      cirrhosis (all with gastroesophageal varices), 7/7 (100%) patients with cirrhotic
      PBC (5/7 with gastroesophageal varices), and 3/3 (100%) patients with
      noncirrhotic PBC (none with gastroesophageal varices). The presence of veno
      venous communication was found in 15/29 (51.7%) patients with viral cirrhosis,
      6/7 (85.7%) patients with cirrhotic PBC, and 3/3 (100%) patients with
      noncirrhotic PBC. CONCLUSION: The study suggested that sinusoidal blockage is the
      underlying pathophysiology even in the early-stage PBC, proved by the visible
      intrahepatic portal vein in three noncirrhotic PBC patients, and veno-venous
      communication in the liver is responsible for alleviated hepatic venous pressure
      gradient.

PMID- 25563141
TI  - High local recurrence of early-stage hepatocellular carcinoma after percutaneous
      thermal ablation in routine clinical practice.
AB  - BACKGROUND AND AIM: The risk of local tumour progression (LTP) and factors
      predicting LTP following percutaneous thermal ablation (PTA) of early-stage
      hepatocellular carcinoma (HCC) have not been well studied in non-trial settings
      and may be underestimated. We aimed to assess these outcomes in a multicentre
      study. PATIENTS AND METHODS: This was a retrospective review of consecutive
      patients with early-stage HCC treated with a curative intent across three
      tertiary Australian centres between 2006 and 2012 with either radiofrequency
      ablation or microwave ablation. The primary endpoint was LTP and multivariate
      analysis was carried out to identify the independent predictors of LTP. RESULTS:
      In total 145 HCC nodules were treated in 126 patients (78% men, mean+/-SD age
      62+/-10 years) with a mean+/-SD follow-up of 13.5+/-13 months. Local recurrence
      was observed in 23.4% (34/145). Mean+/-SD LTP-free survival was 46.9+/-3.6
      months. For HCC nodules 2 cm or less, local recurrence rates were lower (15.9%),
      with a mean+/-SD LTP-free survival of 48.8+/-4.2 months. Poorly differentiated
      HCC [hazard ratio (95% confidence interval)=4.8 (1.1-20.4), P=0.032] and
      pretreatment alpha-fetoprotein more than 50 kIU/l [8.2 (1.7-39.0), P=0.008] were
      independent predictors of LTP. LTP rates were not significantly different between
      the radiofrequency ablation and the microwave ablation groups (22.8 vs. 25.8%,
      P=0.7). There were six (4.8%) procedure-related adverse events, but no deaths.
      CONCLUSION: Local recurrence after PTA for early-stage HCC is high in routine
      clinical practice. Poorly differentiated HCC and pretreatment alpha-fetoprotein
      are important, independent predictors of LTP. Further well-designed randomized
      controlled trials with larger sample sizes using adjuvant therapies in
      combination with PTA to decrease LTP rates are warranted.

PMID- 25563142
TI  - Screening for liver cancer during transplant waiting list: a multicenter study
      from South America.
AB  - BACKGROUND AND AIMS: Surveillance during liver transplantation (LT) waiting list
      has scarcely been reported in South America. We aimed to describe hepatocellular
      carcinoma (HCC) surveillance during the LT waiting list in the daily practice.
      PATIENTS AND METHODS: A multicenter retrospective analysis in cirrhotic patients
      was carried out. All patients underwent an ultrasound (US) every 6 months and the
      last pre-LT US was compared with explanted liver findings. A false-negative case
      was considered when incidentally found HCC (iHCC) was detected, whereas a false
      positive case was considered when HCC diagnosed before LT (cHCC) was not
      confirmed in the explanted liver. US performance was assessed after excluding
      cHCC patients referred to transplant evaluation. RESULTS: Of 643 patients, 129
      had HCC, of whom 92 had cHCC (71.3%) and 37 had iHCC (28.7%). Five patients
      (5.4%) had nonconfirmed cHCC (n=3 regenerative nodules, n=1 biliary hamartoma,
      and n=1 cholangiocarcinoma). Patients with iHCC had a higher MELD score (23+/-10
      vs. 15+/-10; P<0.0001), and were more frequently Child-Pugh C (62.2 vs. 36.6%;
      P=0.006) compared with patients with cHCC. The number of US performed during
      waiting list was 1.7+/-1.6 (median 1.0). During transplant waiting list, the
      sensitivity and specificity of US were 33 and 99%, with positive and negative
      predictive values of 0.89 and 0.93, respectively. Multivariate analysis showed
      that the strongest variable related to iHCC finding was pre-LT Child-Pugh C
      status (OR 3.5; P=0.004). CONCLUSION: Screening for liver cancer remains an
      important issue during transplant waiting list. However, the US screening method
      should be reviewed particularly for Child-Pugh C patients.

PMID- 25563143
TI  - Nonalcoholic fatty liver disease as a potential risk factor of cardiovascular
      disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the hepatic component of the
      metabolic syndrome. The aim of this review is to summarize the available data
      linking NAFLD with cardiovascular disease (CVD). The following topics are
      reviewed: (a) the clinical evidence linking NAFLD to increased prevalence of CVD;
      (b) the relationship between NAFLD (which is diagnosed by liver biopsy, serum
      liver enzymes, or ultrasonography) and incidence of CVD; (c) the mechanism
      linking NAFLD to CVD and clinical implication; and (d) the potential impact of
      NAFLD treatment on cardiac complications. CVD dictates the outcome (or outcomes)
      in patients with NAFLD more frequently and to a greater extent than does the
      progression of liver disease. NAFLD patients have a higher risk of all-cause
      death than the general population, mainly because of CVD or liver-related causes.
      The biologic mechanism linking NAFLD and CVD might be associated with various
      factors, involving a complex interaction among insulin resistance, oxidative
      stress, abnormal adipocytokine profile, endothelial dysfunction, lipid
      abnormalities, and activation of inflammatory cascade. Lifestyle modifications
      and pharmacotherapy are helpful to treat patients with NAFLD. NAFLD is likely to
      be associated with an increased risk of CVD, and raises the possibility that
      NAFLD may not only be a marker but also an early mediator of CVD. 

PMID- 25563144
TI  - Hepascore and hyaluronic acid as markers of fibrosis in liver disease of mixed
      aetiology.
AB  - OBJECTIVE: To evaluate hyaluronic acid (HA) and Hepascore as diagnostic
      replacements for liver biopsy in a population with mixed liver disease. MATERIALS
      AND METHODS: The utility of HA concentration and Hepascore for staging fibrosis,
      detecting any fibrosis and detecting advanced fibrosis, was assessed in 73
      consecutive patients, with varied liver pathologies requiring biopsy. Subgroup
      analyses compared utility of disease-specific and universal cut-offs for HA and
      Hepascore. RESULTS: Forty-one patients (56.2%) had liver fibrosis on biopsy. HA
      and Hepascore varied significantly with METAVIR stage, although ranges
      overlapped, precluding their use in staging fibrosis. When detecting any fibrosis
      (METAVIR F1-F4), HA and Hepascore had areas under the receiver operator
      characteristic curve of 0.63 and 0.66, respectively, and approximately two-thirds
      of patients were correctly categorized using optimal cut-offs. For detection of
      advanced fibrosis (METAVIR F3/4), HA and Hepascore had areas under the receiver
      operator characteristic curve of 0.81 and 0.80, respectively, and three-quarters
      of patients were correctly categorized using optimal cut-offs. In subgroup
      analysis, locally derived, disease-specific cut-offs in hepatitis C virus
      patients yielded greatest diagnostic efficiency, whereas the tests performed
      worst in cryptogenic aetiologies. CONCLUSION: HA and Hepascore cannot accurately
      stage hepatic fibrosis in this population. Locally derived, disease-specific cut
      offs for HA gave the higher diagnostic efficiency observed. Although HA and
      Hepascore may be useful where the disease aetiology is known, particularly in
      established hepatitis C virus, the high cost of false positives and false
      negatives are such that neither a reliable enough to replace biopsy without
      substantial further characterization.

PMID- 25563145
TI  - National surveys of avoidable blindness and visual impairment in Argentina, El
      Salvador, Honduras, Panama, Peru, and Uruguay.
AB  - OBJECTIVE: Describe the rationale and methodology of the Rapid Assessment of
      Avoidable Blindness applied in surveys at the national level in 2011-2013 in
      Argentina, El Salvador, Honduras, Panama, Peru, and Uruguay. METHODS: The survey
      includes individuals aged 50 years and older, minimizing required sample sizes,
      which vary from 2 000 to 5 000 people. It uses straightforward sampling and
      examination techniques, and data analysis is automatic and does not require a
      statistician. It is relatively inexpensive, as it does not take a long time, does
      not require expensive ophthalmic equipment, and can be carried out by local
      staff. Reports are generated by the assessment software package. RESULTS:
      Indicators measured are prevalence of blindness and of moderate and severe visual
      impairment (broken down into avoidable causes and cataracts); prevalence of
      aphakia or pseudophakia; cataract surgical coverage; visual outcome of cataract
      surgeries; causes of poor outcomes; access barriers to cataract surgery; and
      cataract surgery service indicators. Results of each survey will be published
      sequentially in successive issues of the Journal, and a final summary article
      will analyze results as a whole and in comparison with the other surveys in this
      group and with those previously published, which will provide a current picture
      of the situation in this group of countries. CONCLUSIONS: The Rapid Assessment of
      Avoidable Blindness is a robust, simple, and inexpensive methodology to determine
      prevalence of blindness and visual impairment as well as eye health service
      coverage and quality. It is a very valuable tool for measuring progress by
      blindness prevention programs and their impact on the population.

PMID- 25563146
TI  - Rapid assessment of avoidable blindness in Uruguay: results of a nationwide
      survey.
AB  - OBJECTIVE: To investigate and describe the prevalence and causes of blindness and
      moderate and severe visual impairment in older adults living in Uruguay. METHODS:
      All individuals aged >= 50 years old living in randomly selected clusters were
      eligible to participate. In each census enumeration unit selected, 50 residents
      aged 50 years and older were chosen to participate in the study using compact
      segment sampling. The study participants underwent visual acuity (VA) measurement
      and lens examination; those with presenting VA (PVA) < 20/60 also underwent
      direct ophthalmoscopy. Moderate visual impairment (MVI) was defined as PVA <
      20/60-20/200, severe visual impairment (SVI) was defined as PVA < 20/200-20/400,
      and blindness was defined as PVA < 20/400, all based on vision in the better eye
      with available correction. RESULTS: Out of 3 956 eligible individuals, 3 729
      (94.3%) were examined. The age- and sex-adjusted prevalence of blindness was 0.9%
      (95% confidence interval (CI): 0.5-1.3). Cataract (48.6%) and glaucoma (14.3%)
      were the main causes of blindness. Prevalence of SVI and MVI was 0.9% (95% CI:
      0.5-1.3) and 7.9% (95% CI: 6.0-9.7) respectively. Cataract was the main cause of
      SVI (65.7%), followed by uncorrected refractive error (14.3%), which was the main
      cause of MVI (55.2%). Cataract surgical coverage was 76.8% (calculated by eye)
      and 91.3% (calculated by individual). Of all eyes operated for cataract, 70.0%
      could see >= 20/60 and 15.3% could not see 20/200 post-surgery. CONCLUSIONS:
      Prevalence of blindness in Uruguay is low compared to other Latin American
      countries, but further reduction is feasible. Due to Uruguay's high cataract
      surgical coverage and growing proportion of people >= 50 years old, the impact of
      posterior pole diseases as a contributing factor to blindness might increase in
      future.

PMID- 25563147
TI  - Depression among diabetic women in urban centers in Mexico and the United States
      of America: a comparative study.
AB  - OBJECTIVE: To compare the prevalence and patterns of depressive symptoms among
      women with type 2 diabetes in Puebla, Mexico, and Chicago, United States.
      METHODS: Two cross-sectional studies were conducted independently, in Puebla
      (September 2010-March 2011) and in Chicago (January-July 2010). Depression
      symptomatology was evaluated in a random sample of 241 women self-reporting type
      2 diabetes in Puebla and a convenience sample of 121 women of Mexican descent
      seeking care for type 2 diabetes in Chicago. Depressive symptomatology was
      measured by the Center for Epidemiologic Studies Depression Scale administered in
      either English or Spanish. Women were similarly socioeconomically disadvantaged
      with low education levels in both locations. RESULTS: The Chicago sample of women
      reported higher levels of depression than the Puebla sample (38% versus 17%, P <
      0.0001). Among those with comorbid depression and diabetes in both sites, minimal
      variations in symptoms were observed. Depressive symptoms, specifically the
      subjective element (feeling sad) and symptoms associated with diabetes (fatigue
      and sleep problems) were heightened in both groups. More frequent reporting of
      "feeling fearful" was statistically significant in Puebla. CONCLUSIONS: Despite a
      higher prevalence of depression among Mexican immigrant women with diabetes in
      the United States compared to Mexico, there was little variation in their
      depressive symptoms, regardless of residence. However, women in Mexico did report
      a higher incidence of fear. Screening for depression in patients with diabetes
      should take into account symptoms of fatigue and sleep and the bi-directional
      relationship of depression and diabetes.

PMID- 25563148
TI  - [Adherence to research reporting guidelines in biomedical journals in Latin
      America and the Caribbean].
AB  - OBJECTIVE: To evaluate the familiarity of the editors of journals indexed in the
      LILACS database with the guidelines for reporting on and publishing research-
      promoted by the EQUATOR Network (Enhancing QUAlity and Transparency Of Health
      Research)-, the journals' requirements for use of the guidelines, and the
      editors' opinions regarding the reasons for the low rate of use. METHODS: LILACS
      editors were surveyed by e-mail about the guidelines and their availability at
      the EQUATOR website, and about the requirements and difficulties in using them.
      RESULTS: Of 802 editors, 16.4% answered the survey. More than half said they were
      not aware of the guidelines (especially STROBE and PRISMA) and 30% were familiar
      with the EQUATOR Network. CONCLUSIONS: The first Latin American and Caribbean
      study on LILACS editors' familiarity with the guidelines revealed that more than
      half of them were not familiar either with the guidelines or the EQUATOR Network.

PMID- 25563150
TI  - Disparities in pediatric leukemia early survival in Argentina: a population-based
      study.
AB  - OBJECTIVE: To identify disparities-using recursive partitioning (RP)-in early
      survival for children with leukemias treated in Argentina, and to depict the main
      characteristics of the most vulnerable groups. METHODS: This secondary data
      analysis evaluated 12-month survival (12-ms) in 3 987 children diagnosed between
      2000 and 2008 with lymphoid leukemia (LL) and myeloid leukemia (ML) and
      registered in Argentina's population-based oncopediatric registry. Prognostic
      groups based on age at diagnosis, gender, socioeconomic index of the province of
      residence, and migration to a different province to receive health care were
      identified using the RP method. RESULTS: Overall 12-ms for LL and ML cases was
      83.7% and 59.9% respectively. RP detected major gaps in 12-ms. Among 1-10-year
      old LL patients from poorer provinces, 12-ms for those who did and did not
      migrate was 87.0% and 78.2% respectively. Survival of ML patients < 2 years old
      from provinces with a low/medium socioeconomic index was 38.9% compared to 62.1%
      for those in the same age group from richer provinces. For 2-14-year-old ML
      patients living in poor provinces, patient migration was associated with a 30%
      increase in 12-ms. CONCLUSIONS: Major disparities in leukemia survival among
      Argentine children were found. Patient migration and socioeconomic index of
      residence province were associated with survival. The RP method was instrumental
      in identifying and characterizing vulnerable groups.

PMID- 25563149
TI  - Patient attrition from the HIV antiretroviral therapy program at two hospitals in
      Haiti.
AB  - OBJECTIVE: To identify factors associated with antiretroviral therapy (ART)
      attrition among patients initiating therapy in 2005-2011 at two large, public
      sector department-level hospitals, and to inform interventions to improve ART
      retention. METHODS: This retrospective cohort study used data from the iSante
      electronic medical record (EMR) system. The study characterized ART attrition
      levels and explored the patient demographic, clinical, temporal, and service
      utilization factors associated with ART attrition, using time-to-event analysis
      methods. RESULTS: Among the 2 023 patients in the study, ART attrition on average
      was 17.0 per 100 person-years (95% confidence interval (CI): 15.8-18.3). In
      adjusted analyses, risk of ART attrition was up to 89% higher for patients living
      in distant communes compared to patients living in the same commune as the
      hospital (hazard ratio: 1.89, 95%CI: 1.54-2.33; P < 0.001). Hospital site,
      earlier year of ART start, spending less time enrolled in HIV care prior to ART
      initiation, receiving a non-standard ART regimen, lacking counseling prior to ART
      initiation, and having a higher body mass index were also associated with
      attrition risk. CONCLUSIONS: The findings suggest quality improvement
      interventions at the two hospitals, including: enhanced retention support and
      transportation subsidies for patients accessing care from remote areas;
      counseling for all patients prior to ART initiation; timely outreach to patients
      who miss ART pick-ups; "bridging services" for patients transferring care to
      alternative facilities; routine screening for anticipated interruptions in future
      ART pick-ups; and medical case review for patients placed on non-standard ART
      regimens. The findings are also relevant for policymaking on decentralization of
      ART services in Haiti.

PMID- 25563151
TI  - [Road safety measures and their effects on traffic injuries: a systematic
      review].
AB  - OBJECTIVE: To identify and summarize the findings of studies describing
      interventions aimed at reducing road traffic injuries. METHODS: An integrative
      systematic review without meta-analysis was performed. The Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) were used to synthesize
      the findings of the articles reviewed. The keywords "traffic accidents", "review"
      and "public policy" were used in isolation or combined with boolean operator
      "And" to search PubMed, Web of Science, SciELO, and LILACS for the period between
      2006 and 2011 RESULTS: Twenty-two studies were included in the systematic review.
      Of these, two described engineering strategies, two described other road safety
      policies, three described education strategies, and 15 described law enforcement
      policies. Law enforcement had the most effective immediate results. Engineering
      strategies proved important to promote a safe environment. Finally, education
      strategies had an informative role and served to support other strategies, but
      did not seem sufficient to promote cultural changes regarding road safety.
      CONCLUSIONS: Law enforcement seems to be the most effective strategy to change
      the behavior of drivers, especially regarding speed limits and drinking and
      driving.

PMID- 25563152
TI  - Call for a change in research funding priorities: the example of mental health in
      Costa Rica.
AB  - The World Health Organization (WHO) Mental Health Action Plan 2013-2020 urges its
      Member States to strengthen leadership in mental health, ensure mental and social
      health interventions in community-based settings, promote mental health and
      strengthen information systems, and increase evidence and research for mental
      health. Although Costa Rica has strongly invested in public health and
      successfully reduced the burden of nutritional and infectious diseases, its
      transitional epidemiological pattern, population growth, and immigration from
      unstable neighboring countries has shifted the burden to chronic disorders.
      Although policies for chronic disorders have been in place for several decades,
      mental disorders have not been included. Recently, as the Ministry of Health of
      Costa Rica developed a Mental Health Policy for 2013-2020, it became evident that
      the country needs epidemiological data to prioritize evidence-based intervention
      areas. This article stresses the importance of conducting local epidemiological
      studies on mental health, and calls for changes in research funding priorities by
      public and private national and international funding agencies in order to follow
      the WHO Mental Health Action Plan. 

PMID- 25563153
TI  - [Prescription drug monitoring programs in the United States of America].
AB  - Since the late 1990s, the number of opioid analgesic overdose deaths has
      quadrupled in the United States of America (from 4 030 deaths in 1999 to 16 651
      in 2010). The objectives of this article are to provide an overview of the
      problem of prescription drug overdose in the United States and to discuss actions
      that could help reduce the problem, with particular attention to the
      characteristics of prescription drug monitoring programs (PDMPs). These programs
      consist of state-level databases that monitor controlled substances. The
      information compiled in the databases is at the disposal of authorized persons
      (e.g., physicians, pharmacists, and other health-care providers) and may be used
      only for professional purposes. Suppliers can use such information to prevent
      interaction with other drugs or therapeutic duplication, or to identify drug
      search behavior. Law enforcement agencies can use these programs to identify
      improper drug prescription or dispensing patterns, or drug diversion. 

PMID- 25563154
TI  - Acute Chickungunya: emergence of a new, viral pathogen in the Caribbean.

PMID- 25563156
TI  - [Access to medicines and pharmaceutical market situation in Ecuador].

PMID- 25563155
TI  - Young leaders in public health in Latin America and the Caribbean: insights from
      the eSAC project.

PMID- 25563157
TI  - Serum hormone concentrations and ovarian follicular wave emergence in Jilin sika
      deer (Cervus nippon hortulorum) after synchronization of estrous cycles.
AB  - The study was conducted to investigate the serum hormone concentrations and
      follicular dynamics present after synchronous treatment (CIDR) in female Jilin
      sika deer (n = 15) of estrous cycles. Blood samples were collected to analyze the
      FSH, LH, estradiol and progesterone during the estrous cycles. Manual transrectal
      ultrasonography examination was conducted at least thrice weekly to monitor the
      follicular wave. Ultrasonography showed that follicle development occurred in
      waves, and most estrous cycles in Jilin sika deer consist of one, two, or three
      waves. The largest follicles of the interwaves of two- and three-wave cycles were
      different (P < 0.05). The mean interovulatory interval was 15.0 +/- 4.6 d. There
      was a surge in circulating FSH in two- and three-wave cycles. The emergence of
      the largest follicle was related to the peak of serum concentration of estradiol.
      Serum progesterone concentrations were not different between one- and three-wave
      cycles (P < 0.05). We concluded that FSH and estradiol concentration may have an
      important role in controlling follicular development, that the estrous cycle in
      Jilin sika deer is characterized by one, two, or three waves of follicular
      development after synchronization.

PMID- 25563158
TI  - Using nestling plasma to assess long-term spatial and temporal concentrations of
      organochlorine compounds in bald eagles within Voyageurs National Park,
      Minnesota, USA.
AB  - The bald eagle (Haliaeetus leucocephalus) population at Voyageurs National Park
      (VNP) provides an opportunity to assess long-term temporal and spatial trends of
      persistent environmental contaminants. Nestling bald eagle plasma samples
      collected from 1997 to 2010 were analyzed for polychlorinated biphenyls (PCBs)
      and organochlorine pesticides. Trends of total PCBs, total DDTs, 4,4'-DDE, and
      Dieldrin were analyzed since >50% of nestling plasma samples had detectable
      concentrations. Total PCBs, total DDTs, and 4,4'-DDE concentrations have all
      decreased over time (26.09%, 24.09%, and 40.92% respectively). Concentrations of
      Dieldrin have increased by 50.25%. In this study, 61.1% of all nestlings sampled
      had detectable concentrations of Dieldrin from all time periods and all areas of
      VNP. Since Dieldrin is a banned pesticide in North America, the source of this
      increase is unknown. However, increases and fluctuations in Dieldrin
      concentration suggest contaminant levels in VNP may be linked to a new source or
      environmental process. 

PMID- 25563160
TI  - Theoretical study on the atmospheric transformation mechanism of pirimiphos
      methyl initiated by O3.
AB  - Pirimiphos-methyl (PMM) is a widely used organophosphorus pesticide that can be
      released into the atmosphere in gas and condensed phases. It possesses a PS bond
      and an N,N-dialkyl group adjacent to pyrimidine, which are common functional
      groups for pesticides. Currently, the reaction mechanisms of O3 with these
      functional groups are poorly understood. In this study, the mechanisms and
      possible degradation products for O3-initiated atmospheric oxidation of PMM were
      investigated using the Density Functional Theory (DFT) method. The results show
      that H abstraction from the alpha carbon of the N,N-diethyl group and its
      subsequent reactions (hydroxylation, N-dealkylation, and carbonylation
      reactions), as well as the transformation of the PS bond to the PO oxone form,
      are the most favorable reaction pathways for PMM and O3. The Gibbs free energy
      (DeltaG) indicates that the subsequent reactions tend to take place more
      spontaneously once the initial reaction occurs. In addition, theoretical
      calculations indicate that water can serve as an effective catalyst in the N
      dealkylation reaction process. Water-assisted reactions lead to the activation
      energy decreasing by 20.2 kcal mol(-1) compared with direct reactions, and thus
      may represent a dominant reaction pathway for the N-dealkylation process in the
      atmosphere. These theoretical results provide new insights into O3-initiated
      degradation of PMM and its analogues.

PMID- 25563159
TI  - Efficient removal of sulcotrione and its formulated compound Tangenta(r) in
      aqueous TiO2 suspension: Stability, photoproducts assessment and toxicity.
AB  - The photocatalytic degradation of the herbicide sulcotrione (0.05 mM) and its
      formulated compound Tangenta(r) in aqueous suspensions of TiO2 Degussa P25 was
      examined as a function of the different operational parameters. The optimum of
      the catalyst loading was found to be 2.0 mg mL(-1) under UVA light. In the first
      stage of the reaction, the photocatalytic degradation of sulcotrione alone and in
      Tangenta(r) followed the pseudo-first order kinetics, in which the heterogeneous
      catalysis proceeds via OH and holes. Further, it can be concluded that
      degradation rate of sulcotrione alone is about two times higher compared to
      formulated compound. The results showed that the disappearance of sulcotrione led
      to the formation of three organic intermediates and ionic byproducts (Cl(-),
      SO4(2-), acetate and formate), whereas their mineralization was about 90% after 4
      h. Tentative photodegradation pathways were proposed and discussed. Also, there
      was no significant toxicity observed after the irradiation of sulcotrione
      solution and Tangenta(r) formulation using TiO2 catalyst on three mammalian cell
      lines.

PMID- 25563162
TI  - Fate and transport of petroleum hydrocarbons in engineered biopiles in polar
      regions.
AB  - A dynamic multi-media model that includes temperature-dependency for partitioning
      and degradation was developed to predict the behaviour of petroleum hydrocarbons
      during biopiling at low temperature. The activation energy (Ea) for degradation
      was derived by fitting the Arrhenius equation to hydrocarbon concentrations from
      temperature-controlled soil mesocosms contaminated with crude oil and diesel. The
      model was then applied to field-scale biopiles containing soil contaminated with
      diesel and kerosene at Casey Station, Antarctica. Temporal changes of total
      petroleum hydrocarbons (TPH) concentrations were very well described and
      predictions for individual hydrocarbon fractions were generally acceptable
      (disparity between measured and predicted concentrations was less than a factor
      two for most fractions). Biodegradation was predicted to be the dominant loss
      mechanism for all but the lightest aliphatic fractions, for which volatilisation
      was most important. Summertime losses were significant, resulting in TPH
      concentrations which were about 25% of initial concentrations just 1 year after
      the start of treatment. This contrasts with the slow rates often reported for
      hydrocarbons in situ and suggests that relatively simple remediation techniques
      can be effective even in Antarctica.

PMID- 25563161
TI  - Photo-transformation of pedogenic humic acid and consequences for Cd(II), Cu(II)
      and Pb(II) speciation and bioavailability to green microalga.
AB  - Humic substances (HS) play key role in toxic metal binding and protecting aquatic
      microorganisms from metal-induced stress. Any environmental changes that could
      alter HS concentration and reactivity can be expected to modify metal
      complexation and thus affect metal speciation and bioavailability to microalgae.
      The present study explores the influence of increased solar irradiance on the
      chemical structures and molecular weight of Elliott soil humic acid (EHA) and the
      associated consequences for Cd(II), Cu(II) and Pb(II) complexation and
      intracellular metal content in microalga. The results demonstrate that high
      radiance doses induce an oxidation of EHA with a formation of low molecular
      weight acids, an increase of -OH and -COOH group abundance, and a drop in EHA
      hydrodynamic size and molecular weight. The photo-induced structural changes are
      accompanied with a release of metal from M-EHA complexes and narrowing their size
      distribution, which in turn results in an increase of the intracellular Cd, Cu
      and Pb contents in microalga Chlamydomonas reinhardtii in agreement with the
      measured free metal ions concentrations. 

PMID- 25563163
TI  - Primary risk assessment of dimethyldithiocarbamate, a dithiocarbamate fungicide
      metabolite, based on their probabilistic concentrations in a coastal environment.
AB  - The primary ecological risk of dimethyldithiocarbamate (DMDC), a dithiocarbamate
      fungicide (DTC) metabolite, was evaluated based on their probabilistic
      environmental concentration distributions (ECDs) in the coastal environment,
      Hiroshima Bay, Japan. And their behavior and temporal trends was further
      considered. This is the first report of the identification of DMDC from
      environmental seawater and sediment samples. DMDC concentrations in bottom
      seawater were substantially higher than those in surface seawater, which are
      associated with the leachability from sediments in bottom seawaters, and with
      photodegradation in surface seawaters. Furthermore, seasonal risks are dominated
      by higher concentrations from April to June, indicating temporal variation in the
      risk to exposed species. Hierarchical Bayesian analysis offered DMDC ECD medians
      and range (5th to 95th percentiles) of 0.85 ng L(-1) (0.029, 22), 12 ng L(-1)
      (3.2, 48) and 110 ng kg dry(-1) (9.5, 1200) in surface seawater, bottom seawater
      and sediment, respectively. Considering that DMDC and DTCs have similar
      toxicological potential to aquatic organisms, the occurrence of the compound in
      water is likely to be of biological relevance. In summary, this work provides the
      first demonstration that the ecological risk of DMDC and its derived DTCs in
      Hiroshima Bay is relatively high, and that DTCs should be a high priority for
      future research on marine contamination, especially in bottom seawaters.

PMID- 25563164
TI  - Aero-dispersed mutagenicity attributed to particulate and semi volatile phase in
      an urban environment.
AB  - Commonly the atmospheric pollution research is focussed on particulate indicators
      especially when mutagenicity was studied. On the other hand the volatile and semi
      volatile compounds no adsorbed on to the particles can be genotoxic and
      mutagenic. Moreover some mutagenic compounds, such as polycyclic aromatic
      hydrocarbons, are present both in the particulate and in the gas-phase in
      according to chemical conditions. This work is focussed on the assessing of the
      total mutagenicity shifting the gas-phase and particulate phase, during two
      seasons, in Turin. Two sampling sessions are conducted for total particulate
      matter and gas-phase pollutants. Moreover meteorological and usual air pollution
      monitoring data were collected at the same sampling station. The Salmonella assay
      using the strains TA98 and YG1021 was conducted on each organic extract. The mean
      level of total suspended particles, PM10 and PM2.5 were 73.63+/-26.94, 42.85+/
      26.75 and 31.55+/-26.35 MUg m(-)(3). The observed mutagenicity was PM induced
      YG1021>PM induced TA98>PM induced TA98+S9?non-particle induced YG1021>non
      particle induced TA98>non-particle induced TA98+S9. The multivariate regression
      is significant when we consider air pollution and meteorological indicators and
      chemical conditions as predictors.

PMID- 25563166
TI  - Field study on the uptake and translocation of PBDEs by wheat (Triticum aestivum
      L.) in soils amended with sewage sludge.
AB  - Field experiments were conducted to explore the effects of different sewage
      sludge amendment strategies on the accumulation and translocation of
      polybrominated diphenyl ethers (PBDEs) in soil-wheat systems. Two types of
      application methods (single or annual application) and four annual application
      rates (5, 10, 20, and 40 t ha(-1) year(-1)) were investigated. BDE 209 was
      detected in all of the sewage sludge amended soils and different parts of wheat
      plants collected from the contaminated soils. However, the other seven PBDE
      congeners (BDE 28, BDE 47, BDE 99, BDE 100, BDE 153, BDE 154, and BDE 183) were
      not detected or were only observed at very low levels. A single application of
      sewage sludge in large quantities would likely increase accumulation of BDE 209
      in soil and its subsequent uptake and translocation by wheat. The concentrations
      of BDE 209 in soils, wheat roots and straws increased with the increasing sewage
      sludge application rate. There is a negative correlation between the root
      accumulation factors (the ratios of concentrations in wheat roots to those in
      soils) and soil total organic carbon (R(2)=0.84,P<0.05), demonstrating that the
      bioavailability of BDE 209 was controlled by the soil total organic carbon. BDE
      209 concentrations in the grains from the sewage sludge amended soils were not
      significantly different from those of the control soils, suggesting that
      atmospheric deposition was the main source of BDE 209 detected in the grains.

PMID- 25563165
TI  - Treatment of high salinity brines by direct contact membrane distillation: Effect
      of membrane characteristics and salinity.
AB  - Direct contact membrane distillation (DCMD) is one of the attractive technologies
      for high salinity brine treatment. In this study, four polytetrafluoroethylene
      (PTFE) membranes were examined in treating highly concentrated salt solutions.
      Results showed that non-supported membranes generally have a higher overall mass
      transfer coefficient but porosity seems to be the most important parameter
      controlling membrane flux and thermal efficiency. Supported membranes with large
      thickness had relatively higher thermal efficiency than small thickness. This can
      be attributed to their reduced heat loss through heat condition. In addition,
      KCl, NaCl and MgCl2 solutions showed distinct trends over flux decline at high
      salt concentrations (?2.0M). The difference in flux was largely due to the
      discrepancy in water activities of these solutions (KCl>NaCl>MgCl2). However, the
      effect of viscosity on permeate flux could not be neglected for MgCl2 at high
      salt concentrations as the suddenly increased viscosity could lead to serious
      temperature polarization. This study indicates that membrane distillation is a
      promising technology for high salinity brine treatment. 

PMID- 25563168
TI  - Theoretical study on the torsional potential of alkyl, donor, and acceptor
      substituted bithiophene: the hidden role of noncovalent interaction and backbone
      conjugation.
AB  - Side chain and substituent engineering of conjugated polymers are important to
      their backbone design. Of particular interest here is how side chains and
      substituents influence the coplanarity of conjugated backbones. Steric hindrance
      is usually considered as the principal factor influencing the coplanarity. In
      this study, we used proper first-principle density functional theories to analyze
      the change in the torsional potentials of substituted bithiophene with
      substituents of varying degrees of electron donating/accepting capabilities.
      Besides steric hindrance, the torsional potential of substituted bithiophene is
      also determined by other factors such as the position of substitution, non
      covalent interactions between the substituents and thiophene ring, and electron
      conjugation in the backbone. There is no significant change in the torsional
      potential unless the substituent group is located at the head position of
      bithiophene. The bulkiness of the substituent group increases the torsional
      barrier at 0 and 180 degree (planar bithiophene), while the weak noncovalent
      interaction (such as CH-pi, NH-pi, and dispersion interactions) stabilizes the
      transition structure and decreases the barrier at 90 degree (two thiophene rings
      in perpendicular). Strong electron-withdrawing substituent groups (e.g., formyl
      or nitro groups) are found to reduce backbone conjugation resulting in reduced
      internal rotation barrier at 90 degree. Any of these factors deteriorates the
      coplanarity of bithiophene. On the other hand, the backbone conjugation can be
      enhanced by introducing electron-donating groups (e.g., methoxy) resulting in an
      increased internal rotational barrier and stabilized planar structure. The
      influence of through-space interactions such as S...O, S...N and CH...O
      interactions are found to play a minor role in the coplanarity of substituted
      bithiophene.

PMID- 25563167
TI  - Selection of organic process and source indicator substances for the
      anthropogenically influenced water cycle.
AB  - An increasing number of organic micropollutants (OMP) is detected in
      anthropogenically influenced water cycles. Source control and effective natural
      and technical barriers are essential to maintain a high quality of drinking water
      resources under these circumstances. Based on the literature and our own research
      this study proposes a limited number of OMP that can serve as indicator
      substances for the major sources of OMP, such as wastewater treatment plants,
      agriculture and surface runoff. Furthermore functional indicators are proposed
      that allow assessment of the proper function of natural and technical barriers in
      the aquatic environment, namely conventional municipal wastewater treatment,
      advanced treatment (ozonation, activated carbon), bank filtration and soil
      aquifer treatment as well as self-purification in surface water. These indicator
      substances include the artificial sweetener acesulfame, the anti-inflammatory
      drug ibuprofen, the anticonvulsant carbamazepine, the corrosion inhibitor
      benzotriazole and the herbicide mecoprop among others. The chemical indicator
      substances are intended to support comparisons between watersheds and technical
      and natural processes independent of specific water cycles and to reduce efforts
      and costs of chemical analyses without losing essential information. 

PMID- 25563169
TI  - Dementia and oral health.

PMID- 25563171
TI  - In vivo and continuous measurement of bisulfide in the hippocampus of rat's brain
      by an on-line integrated microdialysis/droplet-based microfluidic system.
AB  - An on-line and continuous approach was demonstrated for in vivo measurement of
      bisulfide in rat's brain. A modified droplet-based microfluidic system was
      constructed, which allowed on-line qualification of the fluorescence responses of
      the gold nanoparticle-glutathione-fluorescein isothiocyanate probe to the
      variation of bisulfide in the presence of the cerebral microdialysate background.
      The on-line method achieved a dynamic working range from 5.0 MUM to 40 MUM and a
      detection limit of 2.5 MUM. The in vivo bisulfide concentration in the
      hippocampus of rat's brain was measured under different physiological conditions.
      The on-line method may facilitate the study of H2S biology by providing a
      previously unattainable continuous record of H2S variation in living animals. It
      also provides a practical platform for in vivo and continuous monitoring of other
      important species in cerebral systems. 

PMID- 25563172
TI  - Concave gold nanocube assemblies as nanotraps for surface-enhanced Raman
      scattering-based detection of proteins.
AB  - SERS detection of proteins is typically performed by using labeling agents with
      stable and high Raman scattering cross sections. This is a valuable approach for
      trace detection and quantification of a target protein but is unsuitable for
      inspecting its inherent structural and functional properties. On the other hand,
      direct SERS of proteins has been mainly devoted to the study of short peptides
      and aminoacid sequences or of prosthetic groups with intense Raman signals, which
      is of scarce interest for a thorough characterization of most proteins. Here we
      try to overcome these limitations by setting-up an effective platform for the
      structural SERS analysis of proteins. The platform consists of an extended
      bidimensional array of gold concave nanocubes (CNCs) supported on a PDMS film.
      CNCs are closely-packed through face-face and face-corner interactions generating
      a monolayered arrangement featuring well distributed nanoholes. Here the protein
      homogeneously experiences an E-field enhancement outward from the metal surfaces
      surrounding it, which causes a large number of vibrations to be contemporarily
      amplified. The proposed platform provides stable and detailed SERS spectra and
      confers rapidity and reproducibility to the analysis. 

PMID- 25563170
TI  - HPV16 early gene E5 specifically reduces miRNA-196a in cervical cancer cells.
AB  - High-risk human papillomavirus (HPV) type 16, which is responsible for greater
      than 50% of cervical cancer cases, is the most prevalent and lethal HPV type.
      However, the molecular mechanisms of cervical carcinogenesis remain elusive,
      particularly the early steps of HPV infection that may transform normal cervical
      epithelium into a pre-neoplastic state. Here, we report that a group of microRNAs
      (microRNAs) were aberrantly decreased in HPV16-positive normal cervical tissues,
      and these groups of microRNAs are further reduced in cervical carcinoma. Among
      these miRNAs, miR196a expression is the most reduced in HPV16-infected tissues.
      Interestingly, miR196a expression is low in HPV16-positive cervical cancer cell
      lines but high in HPV16-negative cervical cancer cell lines. Furthermore, we
      found that only HPV16 early gene E5 specifically down-regulated miRNA196a in the
      cervical cancer cell lines. In addition, HoxB8, a known miR196a target gene, is
      up-regulated in the HPV16 cervical carcinoma cell line but not in HPV18 cervical
      cancer cell lines. Various doses of miR196a affected cervical cancer cell
      proliferation and apoptosis. Altogether, these results suggested that HPV16 E5
      specifically down-regulates miR196a upon infection of the human cervix and
      initiates the transformation of normal cervix cells to cervical carcinoma. 

PMID- 25563173
TI  - G protein-coupled receptors: an overview of signaling mechanisms and screening
      assays.
AB  - The existence of cellular receptors, a group of specialized biomolecules to which
      endogenous and exogenous compounds bind and exert an effect, is one of the most
      exciting aspects of cell biology. Among the different receptor types recognized
      today, G-protein-coupled receptors (GPCRs) constitute, undoubtedly, one of the
      most important classes, in part due to their versatility, but particularly, due
      to their central role in a multitude of physiological states. The unveiling of
      GPCR function and mode of action is a challenging task that prevails until our
      days, as the full potential of these receptors is far from being established.
      Such an undertaking calls for a joint effort of multidisciplinary teams that must
      combine state-of-the-art technologies with in-depth knowledge of cell biology to
      probe such specialized molecules. This review provides a concise coverage of the
      scientific progress that has been made in GPCR research to provide researchers
      with an updated overview of the field. A brief outline of the historical
      breakthroughs is followed by a discussion of GPCR signaling mechanisms and by a
      description of the role played by assay technologies. 

PMID- 25563174
TI  - Time-resolved FRET strategy to screen GPCR ligand library.
AB  - Screening chemical libraries to find specific drugs for G protein-coupled
      receptors is still of major interest. Indeed, because of their major roles in all
      physiological functions, G protein-coupled receptors remain major targets for
      drug development programs. Currently, interest in GPCRs as drug targets has been
      boosted by the discovery of biased ligands, thus allowing the development of
      drugs not only specific for one target but also for the specific signaling
      cascade expected to have the therapeutic effect. Such molecules are then expected
      to display fewer side effects. To reach such a goal, there is much interest in
      novel, efficient, simple, and direct screening assays that may help identify any
      drugs interacting with the target, these being then analyzed for their biased
      activity. Here, we present an efficient strategy to screen ligands on their
      binding properties. The method described is based on time-resolved FRET between a
      receptor and a ligand. This method has already been used to develop new assays
      called Tag-lite((r)) binding assays for numerous G protein-coupled receptors,
      proving its broad application and its power. 

PMID- 25563175
TI  - Homogeneous fluorescence anisotropy-based assay for characterization of ligand
      binding dynamics to GPCRs in budded baculoviruses: the case of Cy3B-NDP-alpha-MSH
      binding to MC4 receptors.
AB  - Despite the availability of numerous conceptually different approaches for the
      characterization of ligand-receptor interactions, there remains a great
      requirement for complementary methods that are suitable for kinetic studies,
      especially for the characterization of membrane protein systems and G protein
      coupled receptors (GPCRs) in particular. One of the potential approaches that
      inherently fits well for this purpose is fluorescence anisotropy (FA), a method
      that allows continuous monitoring of ligand binding processes and
      characterization of ligand binding dynamics. However, significant changes in FA
      signal of fluorescently labeled ligands can be detected only if the ratio of
      bound to free fluorescent ligand portions is altered, which means that receptor
      and ligand concentrations have to be comparable. As most of the GPCRs are
      normally present at relatively low concentrations in native tissues and
      conventional receptor preparations from overexpressed systems often generate high
      background levels due to significant autofluorescence, receptor preparations with
      sufficiently high receptor concentrations have become a critical requirement for
      successful FA assay performance. We propose that budded baculoviruses that
      display GPCRs on their surfaces can be used as a receptor source in FA assays.
      Here, we describe the experimental setup of this homogeneous budded
      baculovirus/FA-based assay system for investigation of receptor-ligand
      interactions and a novel strategy for FA kinetic data analysis that is taking
      into account the effect of nonspecific interactions and the depletion of the
      fluorescent ligand during the binding reaction. The developed budded
      baculovirus/FA-based assay system brings the experimental data to a level that
      could solve complex models of ligand-receptor interactions and become a valuable
      tool for the screening of pharmacologically active compounds. Melanocortin 4
      (MC4) receptors and the fluorescent ligand Cy3B-NDP-alpha-MSH were used as the
      model system. 

PMID- 25563176
TI  - Construction of recombinant HEK293 cell lines for the expression of the
      neurotensin receptor NTSR1.
AB  - G protein-coupled receptors (GPCRs) are associated with a wide array of diseases
      and are targets of most of the medicines sold worldwide. Despite their clinical
      importance, only 25 unique GPCR structures have been determined as of April 2014.
      The first step for structural studies is to establish the expression of correctly
      folded, functional receptors in recombinant host cells at quantities to allow
      subsequent purification and crystallization trials. Here we describe the T-RExTM
      inducible expression system to construct and select a stable HEK293 cell line for
      high-level expression of functional neurotensin receptor type I (NTSR1). We also
      present the protocols used for the adaptation of the cells into suspension
      culture, as well as the optimization of the induction parameters for NTSR1
      expression, which led to 1 mg of purified NTSR1 per liter suspension culture in
      bioreactors. 

PMID- 25563177
TI  - cAMP assay for GPCR ligand characterization: application of BacMam expression
      system.
AB  - Cyclic adenosine monophosphate (cAMP) is a second messenger of many G-protein
      coupled receptors. The change in cellular cAMP level has widely been used to
      estimate the biological activity of various GPCR-specific agents. Forster
      resonance energy transfer (FRET) biosensors have been around for almost 10 years
      and became increasingly popular for cAMP detection. Ratiometric sensitized
      emission assay of a FRET biosensor can easily be implemented on fluorescence
      plate reader platforms. For such assays a considerable amount of cells expressing
      the desired biosensor is needed. A method to achieve sufficient and reproducible
      level of cAMP biosensor protein expression with the means of BacMam transduction
      system is the subject of this chapter. 

PMID- 25563178
TI  - Ca2+ mobilization assays in GPCR drug discovery.
AB  - Intracellular calcium mobilization can be measured using several methods varying
      in indicator dyes and devices used. In this chapter, we describe the fluorescence
      based method (FLIPR Calcium 4 Assay) developed by Molecular Devices for a
      FlexStation and routinely used in our laboratory for detecting intracellular
      calcium changes. The assay is designed to study calcium mobilization induced by
      majority of GPCRs and calcium channels and allows for simultaneous concentration
      dependent analysis of several receptor agonists and antagonists, useful in
      receptor characterization and drug discovery projects. 

PMID- 25563179
TI  - Using constitutive activity to define appropriate high-throughput screening
      assays for orphan g protein-coupled receptors.
AB  - Orphan G protein-coupled receptors represent an underexploited resource for drug
      discovery but pose a considerable challenge for assay development because their
      cognate G protein signaling pathways are often unknown. In this methodological
      chapter, we describe the use of constitutive activity, that is, the inherent
      ability of receptors to couple to their cognate G proteins in the absence of
      ligand, to inform the development of high-throughput screening assays for a
      particular orphan receptor. We specifically focus on a two-step process, whereby
      constitutive G protein coupling is first determined using yeast Gpa1/human G
      protein chimeras linked to growth and beta-galactosidase generation. Coupling
      selectivity is then confirmed in mammalian cells expressing endogenous G proteins
      and driving accumulation of transcription factor-fused luciferase reporters
      specific to each of the classes of G protein. Based on these findings, high
      throughput screening campaigns can be performed on the already miniaturized
      mammalian reporter system. 

PMID- 25563180
TI  - Monitoring G protein-coupled receptor activation using the protein fragment
      complementation technique split TEV.
AB  - G protein-coupled receptors (GPCRs) modulate cellular signaling, often in a
      ligand-specific manner. Cellular effects regulated include differentiation,
      proliferation, hormonal regulation, and neuronal activity. Further, they are
      involved in many disease-relevant processes, such as cancer and
      neurodevelopmental diseases, and represent the largest class of drug targets.
      Therefore, monitoring how GPCRs are regulated in their activity is crucial to
      understand their role in physiological processes and implications for drug
      development. Split TEV, a method based on TEV protease fragment complementation,
      can be used to sensitively assay GPCR activities in living cells. The activity of
      a given GPCR is monitored through its binding to beta-arrestin. Split TEV
      reporters provide at minimum a two-step amplification process facilitating a
      flexible format and a robust readout. For the initial setup, a GPCR of interest
      and beta-arrestin are fused to the N- and C-terminal fragments of the TEV
      protease, and occurred interactions are indicated by increased fluorescence or
      luminescence of TEV cleavage-dependent reporters. The experimental procedure
      takes 24-72 h to complete, depending on the cell type and complexity of the
      experimental setup applied. 

PMID- 25563181
TI  - Quantifying GPCR internalization: a focus on the Kisspeptin receptor.
AB  - GPCR internalization is a critical regulatory step in determining receptor
      activity. While internalization terminates G protein-coupled signaling, it might
      be required for G protein-independent signaling. A large number of clinical
      therapies are based on preventing or promoting GPCR internalization. Thus, for
      any given GPCR, it is important to characterize its internalization and
      understand the factors that regulate such internalization. Here we describe
      different experimental protocols to evaluate the internalization of any GPCR
      transiently expressed in HEK 293 cells. The protocols describe the use of
      immunofluorescence and imaging techniques as well as flow cytometry. The
      techniques described use the FLAG-tagged kisspeptin receptor (KISS1R) as an
      example but are equally applicable to any other GPCR. 

PMID- 25563182
TI  - GPCR oligomerization analysis by means of BRET and dFRAP.
AB  - The spatiotemporal characterization of protein-protein interactions is essential
      to understand nearly all cellular events. Several methodological strategies
      derived from noninvasive luminescence- and fluorescence-based approaches allow
      the detection of specific protein-protein interactions in living cells. Here, we
      describe the application of bioluminescence resonance energy transfer (BRET) and
      donor fluorescent recovery after photobleaching (dFRAP) approaches to the study
      of G protein-coupled receptor (GPCR) oligomerization. These technologies alone -
      or in combination with complementary methods - can become extremely powerful
      approaches for visualizing these cellular protein-protein interactions, even
      between more than two proteins. Overall, these methods might become extremely
      important tools in GPCR drug discovery. 

PMID- 25563183
TI  - Use of ImageJ to recover information from individual cells in a G protein-coupled
      receptor assay.
AB  - Live-cell assays used in GPCR research often rely on fluorescence techniques that
      generate large amounts of raw image data. Consequently, the capacity to
      accurately and timely extract useful information from image and video data has
      become more and more important. Image J is an open-source program that provides
      powerful tools with a simple interface designed to fit the needs of image
      analysis of most researchers. In this chapter, Image J routines to extract
      information from individual cells in a calcium GPCR assay are described. In these
      routines, individual cells in the same image/video data can be separated using
      either a progressive threshold or a local threshold method. Both methods can be
      optimized to either a maximum number of selection or maximum area selected
      resulting in conceptually distinct selections. 

PMID- 25563184
TI  - Methods to immobilize GPCR on the surface of SPR sensors.
AB  - The G protein-coupled receptors (GPCRs) form one of the largest membrane receptor
      families. The nature of the ligands that interact with these receptors is highly
      diverse; they include light, peptides and hormones, neurotransmitters, and small
      molecular weight compounds. The GPCRs are involved in a wide variety of
      physiological processes and thus hold considerable therapeutic potential.GPCR
      function is usually determined in cell-based assays, whose complexity nonetheless
      limits their use. The use of alternative, cell-free assays is hampered by the
      difficulties in purifying these seven-transmembrane domain receptors without
      altering their functional properties. Several methods have been proposed to
      immobilize GPCR on biosensor surfaces which use antibodies or avidin-/biotin
      based capture procedures, alone or with reconstitution of the GPCR physiological
      microenvironment. Here we propose a method for GPCR immobilization in their
      native membrane microenvironment that requires no manipulation of the target
      receptor and maintains the many conformations GPCR can adopt in the cell
      membrane. 

PMID- 25563185
TI  - Olfactory receptor screening assay using nanovesicle-immobilized carbon nanotube
      transistor.
AB  - Olfactory receptor (OR) genes are considered to be the largest superfamily of the
      mammalian genome, and in the case of humans, approximately 390 kinds of
      functional ORs play a role in perceiving odors. In spite of their significance in
      olfaction, the function of all ORs has not yet been fully revealed. In order to
      efficiently identify specific ligands of orphan ORs, methods that can generate
      olfactory signals in a reliable manner and that can convert the cellular signals
      into measurable responses are required. Here, we describe an OR screening assay
      method using olfactory sensors that are based on cell-derived nanovesicles
      combined with single-walled carbon nanotube field-effect transistors (SWNT-FETs).
      The nanovesicles contain ORs on their surface membrane and induce influx of
      calcium ions similar to olfactory signal transduction. This ion influx causes an
      electrical current change along the carbon nanotube, and then this change is
      measured by the SWNT-FET sensor. This technique facilitates the simple and rapid
      screening of OR functions. 

PMID- 25563186
TI  - Label-free biosensor assays in GPCR screening.
AB  - About one third of currently marketed drugs target G protein-coupled receptors
      (GPCRs), which form the largest group of transmembrane proteins in the human
      proteome. GPCRs are ubiquitously expressed throughout the human body and play a
      pivotal role in a vast number of physiological and pathophysiological processes.
      Because of their intriguing complexity, their relevance, and yet unexploited
      potential in the treatment of diseases, GPCRs are studied intensively by both
      academic and industrial research labs.Classical biochemical and molecular biology
      techniques, including traditional second messenger assays, took biomedical
      research to the next level and represent the fascinating power of in vitro
      pharmacology. While extremely efficient in capturing one clearly defined cellular
      readout, those methods do not authentically portray the events taking place in
      living cells as a whole; hence the process of drug discovery runs the risk to
      lose sight of a wider context already in early stages. Label-free cell-based
      assays hold the promise to overcome these shortcomings by considering cellular
      processes holistically. If combined with diligent assay adjustments, dynamic mass
      redistribution (DMR) technology is an excellent tool to investigate GPCR
      signaling. In this article we aim to provide guidance for scientists seeking for
      information on how to set up and optimize DMR assays with the objective to
      establish a knowledge base on deciphering integrated cellular readouts. For this
      reason we focus on a basic DMR protocol for the investigation of the long-chain
      fatty acid FFA1 receptor as a model family A GPCR and complement it with
      information that allow a sophisticated approach to more specialized scientific
      questions with the use of this comparatively novel method. 

PMID- 25563187
TI  - Multidimensional GPCR profiling and screening using impedance-based label-free
      and real-time assay.
AB  - GPCRs constitute one of the most sought-after targets in drug discovery because
      they are associated with conditions ranging from cardiovascular diseases,
      autoimmune diseases, inflammation, cancer, and diseases of the nervous system.
      Moreover, they are one of the most amenable targets for drug discovery because
      they can be modulated by small molecules, peptides, proteins, and antibodies.
      Therefore it may not come as a surprise that close to 40 % of the drugs that are
      currently on the market are targeting GPCRs. It has become evident that GPCR
      signaling is highly complex and may involve multiple or a subset of pathways
      depending on the interaction of a GPCR with an agonist or antagonist. It is
      imperative that any functional screening for GPCR activity integrates this
      complexity. In this assay protocol, we describe how the xCELLigence RTCA HT
      impedance-based platform which can be used for functional cell-based GPCR assays
      can be utilized for GPCR screening. 

PMID- 25563188
TI  - Label-free functional selectivity assays.
AB  - G protein-coupled receptors (GPCRs) represent the largest class of drug targets.
      Ligand-directed functional selectivity or biased agonism opens new possibility
      for discovering GPCR drugs with better efficacy and safety profiles. However,
      quantification of ligand bias is challenging. Herein, we present five different
      label-free dynamic mass redistribution (DMR) approaches to assess ligand bias
      acting at the beta2-adrenergic receptor (beta2AR). Multiparametric analysis of
      the DMR agonist profiles reveals divergent pharmacology of a panel of beta2AR
      agonists. DMR profiling using catechol as a conformational probe detects the
      presence of multiple conformations of the beta2AR. DMR assays under
      microfluidics, together with chemical biology tools, discover ligand-directed
      desensitization of the receptor. DMR antagonist reverse assays manifest biased
      antagonism. DMR profiling using distinct probe-modulated cells detects the biased
      agonism in the context of self-referenced pharmacological activity map. 

PMID- 25563189
TI  - Measurement of surface-mediated Ca2+ transients on the single-cell level in a
      microfluidic lab-on-a-chip environment.
AB  - Understanding the dynamics of signal transduction processes that are induced by
      cell-cell or cell-surface interactions requires the physical stimulation of the
      cells of interest on a single-cell level and without any ill-defined contacting
      of their cell membrane. However, standard cell culture techniques are
      inapplicable for this task as they do not provide cell and particle handling at
      sufficiently high spatial and temporal resolution and are limited to ensemble
      measurements. Here, we present a novel process line for the individual
      stimulation of single cells with bioactive surfaces, like other cells or
      particles, and the simultaneous analysis of the induced cytosolic calcium
      signals. The method is based on a microfluidic lab-on-a-chip environment that
      allows for contactless cell and particle handling by dielectrophoretic forces. 

PMID- 25563190
TI  - Cell-based assays and animal models for GPCR drug screening.
AB  - The family of G protein-coupled receptors (GPCRs) remains a central focus of
      basic pharmacology and drug discovery efforts. Convenient methods to assess the
      efficacy of potentially therapeutic reagents for GPCRs are strongly required for
      high-throughput screening (HTS) assay. We recently developed a rapid, sensitive,
      and quantitative method for detecting potential chemicals that act on GPCRs using
      split luciferase complementation. In principle, this is based on the detection of
      interactions of GPCR with beta-arrestin, which translocates to the activated
      GPCRs. This method can facilitate the construction of HTS systems in a multi-well
      plate format. Particularly, the method is compatible with single-cell imaging and
      animal models and even deeper tissues such as organs, because of its high
      sensitivity, suggesting that promising candidates from HTS assay can be moved
      easily to the next phase for additional analysis. This system can contribute to
      the effective evaluation of potentially therapeutic reagents and expedite the
      development of new drugs for GPCRs. 

PMID- 25563191
TI  - Computer-aided design of GPCR ligands.
AB  - The recent availability of several GPCR crystal structures now contributes
      decisively to the perspective of structure-based ligand design. In this context,
      computational approaches are extremely helpful, particularly if properly
      integrated in drug design projects with cooperation between computational and
      medicinal chemistry teams. Here, we present the pipelines used in one such
      project, devoted to the design of novel potent and selective antagonists for the
      different adenosine receptors. The details of the computational strategies are
      described, and particular attention is given to explain how these procedures can
      effectively guide the synthesis of novel chemical entities. 

PMID- 25563192
TI  - Grain size control in the fabrication of large single-crystal bilayer graphene
      structures.
AB  - Bilayer graphene (BLG) can provide a tunable band gap when exposed to a vertical
      electric field. We report here an approach to the synthesis of large single
      crystal BLG structures with diameters up to 0.54 mm. We found that both
      absorption-diffusion and gas-phase penetration mechanisms contributed to the
      growth of the lower second layer and that the absorption-diffusion mechanism
      favors faster BLG growth. Our strategy was to suppress nucleation in the growth
      of the first layer using an established surface oxidation method to maintain a
      low coverage of graphene on Cu foil. We subsequently maximized the growth of the
      second layer by increasing the duration of absorption-diffusion. The chemical
      treatment used to polish the Cu surface to reduce the nucleation of growth in the
      monolayer increased the nucleation density during the growth of the second layer.
      Electron transport measurements on dual-gated field-effect transistors showed
      that the BLG fabricated was of high quality with a sizeable tunable band gap. Our
      approach may have broad applications for the controlled synthesis of bilayers in
      materials chemistry. 

PMID- 25563193
TI  - Comparison of circulating and intratumoral regulatory T cells in patients with
      renal cell carcinoma.
AB  - The clear evidence that tumor-infiltrating lymphocytes (TIL) exists in the tumor
      microenvironment raises the question why renal cell carcinoma (RCC) progresses.
      Numerous studies support the implication of CD4(+)CD25(high) regulatory T (Treg)
      cells in RCC development. We aimed in this study to characterize the phenotype
      and function of circulating and intratumoral Treg cells of RCC patient in order
      to evaluate their implication in the inhibition of the local antitumor immune
      response. Our results demonstrate that the proportion of Treg in TIL was, in
      average, similar to that found in circulating CD4(+) T cells of patients or
      healthy donors. However, intratumoral Treg exhibit a marked different phenotype
      when compared with the autologous circulating Treg. A higher CD25 mean level, HLA
      DR, Fas, and GITR, and a lower CD45RA expression were observed in intratumoral
      Treg, suggesting therefore that these cells are effector in the tumor
      microenvironment. Additionally, intratumoral Treg showed a higher inhibitory
      function on autologous CD4(+)CD25(-) T cells when compared with circulating Treg
      that may be explained by an overexpression of FoxP3 transcription factor. These
      findings suggest that intratumoral Treg could be major actors in the impairment
      of local antitumor immune response for RCC patients. 

PMID- 25563194
TI  - XRCC1 genetic polymorphism acts a potential biomarker for lung cancer.
AB  - Lung cancer is one of the most common but serious cancers in the world. Both the
      X-ray repair cross-complementing group 1 (XRCC1) gene and the human multidrug
      resistance 1 (MDR1) gene are important candidate genes influencing the
      susceptibility to various diseases, including lung cancer. This study aimed to
      assess the correlation of genetic polymorphisms in XRCC1 and MDR1 with the
      susceptibility to lung cancer. In this study, a total of 320 lung cancer patients
      and 346 cancer-free controls in Chinese population were enrolled in this study.
      Data about the clinical characteristics and related risk factors of lung cancer
      were collected by questionnaires. The single-nucleotide polymorphisms (SNPs) of
      XRCC1 and MDR1 genes were genotyped by created restriction site-polymerase chain
      reaction method. Our data showed that the risk for lung cancer increased
      significantly among the variant Arg194Trp (C > T, rs1799782) and Arg399Gln (G >
      A, rs25487) of XRCC1, but there are no significant differences in the allelic and
      genotypic frequencies of c.1564A > T and c.3073A > C of MDR1 between lung cancer
      patients and cancer-free controls. In conclusion, these preliminary results
      suggest that the C > T, rs1799782 and C > T, rs25487 of XRCC1 genetic variants
      might be used as molecular markers for detecting lung cancer susceptibility.

PMID- 25563195
TI  - The methylation of a panel of genes differentiates low-grade from high-grade
      gliomas.
AB  - Epigenetic changes play an important role in the pathogenesis of gliomas and have
      the potential to become clinically useful biomarkers. The aim of this study was
      the evaluation of the profile of promoter methylation of 13 genes selected based
      on their anticipated diagnostic and/or prognostic value. Methylation-specific PCR
      (MSP) was used to assess the methylation status of MGMT, ERCC1, hMLH1, ATM,
      CDKN2B (p15INK4B), p14ARF, CDKN2A (p16INK4A), RASSF1A, RUNX3, GATA6, NDRG2, PTEN,
      and RARbeta in a subset of 95 gliomas of different grades. Additionally, the
      methylation status of MGMT and NDRG2 was analyzed using pyrosequencing (PSQ). The
      results revealed that the methylation index of individual glioma patients
      correlates with World Health Organization (WHO) tumor grade and patient's age.
      RASSF1A, RUNX3, GATA6, and MGMT were most frequently methylated, whereas the
      INK4B-ARF-INK4A locus, PTEN, RARbeta, and ATM were methylated to a lesser extent.
      ERCC1, hMLH1, and NDRG2 were unmethylated. RUNX3 methylation correlated with WHO
      tumor grade and patient's age. PSQ confirmed significantly higher methylation
      levels of MGMT and NDRG2 as compared with normal, non-cancerous brain tissue. To
      conclude, DNA methylation of a whole panel of selected genes can serve as a tool
      for glioma aggressiveness prediction.

PMID- 25563197
TI  - Migration of the penetrated rib head following deformity correction surgery
      without rib head excision in dystrophic scoliosis secondary to type 1
      Neurofibromatosis.
AB  - PURPOSE: Dystrophic scoliosis secondary to Neurofibromatosis type 1 (NF1) may
      predispose to rib penetration into the spinal canal. No clear consensus was
      established regarding whether or not to resect the compressing rib head during
      correction maneuvers. The purpose of this study was to present imaging
      quantification of the migration of intraspinal-dislocated rib head in order to
      assess the extraction degree of dislocated rib heads and the associated
      influencing factors. METHODS: Imaging data of NF1 scoliotic patients with
      intraspinal rib head dislocation from March 1998 to April 2014 were
      retrospectively reviewed. The location and migration of the rib head were
      evaluated in a spinal canal-based coordinate system to calculate their pre- and
      postoperative vector coordinates. Differences in multiple parameters
      representative of rib head position were compared by paired sample t test. We
      also explored whether correction of vertebral rotation and translation could
      contribute to the extraction of intra-canal rib head by linear regression
      analysis. RESULTS: The incidence of apical convex rib head penetration into the
      canal was 15.9 % (23/145). Only 14.8 % of the dislocated rib heads invaded into
      the concave half-circle of the spinal canal, which was reduced to 3.7 %
      postoperatively. The directions of rib head migration were mostly toward the
      anterior convex quadrant of the spinal canal (70.4 %). Paired sample t tests
      revealed significant reduction in intraspinal rib length (9.2 +/- 3.6 vs. 5.2 +/-
      3.6 mm, p < 0.001) and improvement in distance between the rib head tip and the
      most concave spot of the spinal canal (DRCSSC) (14.2 +/- 2.6 vs. 18.1 +/- 3.3 mm,
      p < 0.001). Change of rib-vertebrae angle (RVA) was demonstrated to be positively
      correlated with reduction in intraspinal rib length (beta = 0.534, p = 0.004),
      while Change of RVA (beta = -0.460, p = 0.008) and vertebral translation (VT)
      (beta = -0.381, p = 0.024) was negatively correlated with change of DRCSSC.
      CONCLUSIONS: Spontaneous migration of the dislocated rib head following posterior
      correction surgery resulted in shorter intraspinal rib length and larger
      uninvaded area. More correction of vertebral translation and rib-vertebrae angle
      could increase the degree of extraction from the spinal canal immediately after
      the surgery.

PMID- 25563198
TI  - Transoral anterior release, odontoid partial resection, and reduction with
      posterior fusion for the treatment of irreducible atlantoaxial dislocation caused
      by odontoid fracture malunion.
AB  - PURPOSE: Several techniques have been introduced to manage irreducible
      atlantoaxial dislocation (IAAD). However, no study has reported the surgical
      method for the management of IAAD caused by odontoid fracture malunion. This
      study aimed to introduce a surgical method of transoral anterior release,
      odontoid partial resection, and reduction with sequential posterior fusion for
      the treatment of IAAD caused by odontoid fracture malunion. We also evaluated the
      clinical efficacy of this surgery. METHODS: This study included seven cases of
      IAAD caused by odontoid fracture malunion, collected from January 2008 to January
      2011. Anterior atlantoaxial release was performed through anterior transoral
      approach, followed by partial resection of the odontoid process. C1-C2 were then
      fixed through pedicle screws and rods, and then fused posteriorly by single
      stage. Neurologic status was evaluated using the Japanese Orthopaedic Association
      (JOA) scoring system. RESULTS: All seven patients had complete release, and
      satisfactory reduction. Bony fusion was seen in all patients postoperatively. The
      patients were followed up for an average of 19.6 months (ranged from 9 to 36
      months). The average of patients JOA scores at the final follow-up was
      significantly higher than that of their preoperative scores. Furthermore, the
      average improvement in neurological function was 87.4 %. No screw loosening,
      implant migration or implant failures, atlantoaxial redislocation, or signs of
      instability were observed in any of the patients during the follow-up period.
      CONCLUSIONS: Transoral anterior release, odontoid partial resection, and
      reduction combined with posterior fusion are effective, reliable, and safe
      procedures for the treatment of IAAD caused by odontoid fracture malunion.

PMID- 25563196
TI  - Do postoperative radiographically verified technical success, improved cosmesis,
      and trunk shift corroborate with patient-reported outcomes in Lenke 1C adolescent
      idiopathic scoliosis?
AB  - PURPOSE: To examine correlation between postoperative radiographic and cosmetic
      improvements in Lenke 1C adolescent idiopathic scoliosis (AIS) with patients'
      self-rated outcomes of health and disability at follow-up as determined by the
      Scoliosis Research Society questionnaire (SRS-30), Oswestry Disability Index
      score (ODI) and measure of overall health quality Euroqol-5d (EQ-5D). METHODS: 24
      Lenke 1C scoliosis patients, mean age 16.5 (12.8-38.1) years, treated with
      posterior pedicle screw-only construct, were included. The coronal profile
      indices (radiographic and cosmetic) regarding magnitude of spinal deformity and
      truncal balance were measured preoperatively, postoperatively and at final follow
      up. A comprehensive index of overall back symmetry was also measured by means of
      the Posterior Trunk Symmetry Index (POTSI). Pearson's correlation analysis
      determined the association between the radiographic-cosmetic indices and patient
      rated outcomes. RESULTS: Mean follow-up for the cohort was 4.4 (+/-1.86) years.
      The thoracic apical vertebra-first thoracic vertebra horizontal distance (AV-TI)
      correction had significant correlation with function, self-image, and mental
      health SRS-30 scores (0.55, 0.54, 0.66). Similarly, thoracic apical vertebra
      horizontal translation from central sacral vertical line (AV-CSVL) correction at
      follow-up had significant correlation with self-image and management domains
      (0.57, 0.50). Follow-up POTSI correlated well with SRS-30 and EQ-5D scores (r = 
      0.64, -0.54). Postoperative leftward trunk shift/spinal imbalance did not
      influence overall cosmesis and outcomes; significant spinal realignment was
      evident in follow-up resulting in physiological balance and acceptable cosmesis
      and outcomes. CONCLUSION: Significant, but less than "perfect" correlations were
      observed between the radiographic, cosmetic measures and patient-rated outcomes.
      Thoracic AV-CSVL, AV-T1 correction and POTSI associated significantly with SRS-30
      scores. Whereas, thoracic Cobb angle, Cobb correction, and coronal balance did
      not correlate with any patient-rated outcome measure. It is, therefore, inferred
      that the patients-rated subjective outcomes are only poorly reflected by the
      objectively measured radiographic and cosmetic measures of deformity correction.

PMID- 25563199
TI  - Ponte osteotomies to treat major thoracic adolescent idiopathic scoliosis curves
      allow more effective corrective maneuvers.
AB  - PURPOSE: There is controversy regarding the effect of the Ponte osteotomies in
      the improvement of coronal correction, its maintenance during follow-up, and the
      restoration of thoracic kyphosis in adolescent idiopathic scoliosis (AIS).
      METHODS: Seventy-three AIS patients with Lenke type 1-4 curves were included. A
      prospective description of 43 consecutive patients who underwent apical Ponte
      osteotomies and sublaminar wires with hybrid instrumentation was retrospectively
      compared to a historical cohort of 30 patients without "Ponte osteotomies". The
      surgical details and complications were recorded. We evaluated the radiological
      measurements and SRS-22 Questionnaire scores over a 2-year follow-up. RESULTS:
      The Ponte group achieved better postoperative (70 vs 57 %) and final (62 vs 50 %)
      main curve correction P < 0.001, with no significant loss of correction (4.2
      degrees  vs 2.5 degrees ) P = 0.2 at the final follow-up (48 vs 106 months). We
      did not find a difference in thoracic (T5-T12) postoperative (22 degrees  vs 24
      degrees ) and final (25 degrees  vs 26 degrees ) mean kyphosis angle. However,
      the "Ponte osteotomies" helped to achieve a normal sagittal profile, increasing
      preoperative hypokyphotic curves (<10 degrees ) from 6 degrees  to 17 degrees 
      (control: 9 degrees -12 degrees ; P = 0.01); and preoperative hyperkyphotic
      curves (>40 degrees ) from 52 degrees  to 26 degrees  (control: 46 degrees -39
      degrees ; P = 0.01). The length of surgery was similar (4.3 vs 4.6 h), as were
      the SRS-22 scores. No major complications were found. CONCLUSIONS: Ponte
      osteotomies in major thoracic AIS curves treated by sublaminar wires allowed more
      effective corrective maneuvers, which improved coronal correction without a
      significant loss during follow-up. The sagittal profile appears to be determined
      by other variables; however, "Ponte osteotomies" facilitate the contouring of the
      desired kyphosis.

PMID- 25563200
TI  - Visualization of vascular structure of spinal hemangioblastoma using
      intraoperative indocyanine green videoangiography and temporary feeder occlusion.
AB  - BACKGROUND AND PURPOSE: To more safely resect pathological lesions during spinal
      vascular lesion surgery, it is most important to understand local abnormal
      hemodynamics in detail. New devices or techniques that make out intraoperative
      local hemodynamics have been awaited. To introduce a resourceful method, we
      present a case of spinal hemangioblastoma for which temporary arterial occlusion
      during near-infrared intraoperative indocyanine green (ICG) videoangiography
      gives useful assessment of the main and minor feeders easily. METHODS: A 36-year
      old female suffered progressive paresthesia of both lower extremities for 12
      months and gait disturbance for 2 weeks. A neurological examination revealed T10
      myelopathy. Magnetic resonance imaging (MRI) of the thoracic spine showed an
      intramedullary tumor at the T8 level and severe spinal cord edema with a flow
      void in the extended dorsal spinal veins. Spinal angiography showed a
      hemangioblastoma at the T8 level, with two main feeders and minor feeders.
      RESULTS: She underwent total resection of the tumor by a posterior approach.
      During the intraoperative ICG videoangiography, temporary arterial occlusion of
      the two main feeders and FLOW((r))800 analysis enabled clear understanding of the
      vasculature, especially of the two minor feeders. At the 9-month follow-up, her
      neurological manifestation was partially resolved, and post-operative MRI showed
      total removal of the tumor and disappearance of the spinal cord edema.
      CONCLUSIONS: Temporary clipping of the main feeders during intraoperative ICG
      videoangiography is very useful for easily determining the minor feeding
      arteries, and helpful for maintaining normal perfusion of the spinal cord in
      spinal hemangioblastoma surgery. Furthermore, the FLOW 800 analysis, especially
      the false color-coded variation, increased our understanding of the hemodynamics.

PMID- 25563201
TI  - The effect of DNA supercoiling on nucleosome structure and stability.
AB  - Nucleosomes have to open to allow access to DNA in transcription, replication,
      and DNA damage repair. Changes in DNA torsional strain (e.g. during transcription
      elongation) influence the accessibility of nucleosomal DNA. Here we investigated
      the effect of DNA supercoiling-induced torsional strain on nucleosome structure
      and stability by scanning force microscopy (SFM) and fluorescence correlation
      spectroscopy (FCS). Nucleosomes were reconstituted onto 2.7 kb DNA plasmids with
      varying superhelical densities. The SFM results show a clear dependence of the
      amount of DNA wrapped around the nucleosome core on the strength and type of
      supercoiling. Negative supercoiling led to smaller nucleosome opening angles as
      compared to relaxed or positively supercoiled DNA. FCS experiments show that
      nucleosomes reconstituted on negatively superhelical DNA are more resistant to
      salt-induced destabilization, as seen by reduced H2A-H2B dimer eviction from the
      nucleosome. Our results show that changes in DNA topology, e.g. during
      transcription elongation, affect the accessibility of nucleosomal DNA. 

PMID- 25563202
TI  - MU-Opioid and N-methyl-D-aspartate receptors in the amygdala contribute to
      minocycline-induced potentiation of morphine analgesia in rats.
AB  - The aim of the present study was to investigate the role of the amygdala in the
      potentiative effect of minocycline, a semisynthetic tetracycline antibiotic, on
      morphine analgesia in male Wistar rats. We also examined the involvement of the
      amygdala MU-opioid and N-methyl-D-aspartate (NMDA) receptors in the minocycline
      induced potentiation of morphine analgesia. Intraperitoneal administration of
      morphine (3-9 mg/kg) induced analgesia in a tail-flick test. Bilateral intra
      amygdala injection of minocycline (10-20 MUg/rat) enhanced the analgesic response
      of an ineffective dose of morphine (3 mg/kg). Injection of a higher dose of
      minocycline into the amygdala also induced analgesia. Moreover, bilateral intra
      amygdala injection of naloxone (0.5-1.5 ug/rat) reversed minocycline-induced
      potentiation of morphine analgesia. Pretreatment of animals with NMDA (0.01-0.1
      MUg/rat, intra-amygdala) also inhibited the potentiative effect of minocycline on
      morphine response. Bilateral intra-amygdala injection of the same doses of
      naloxone or NMDA plus morphine had no effect on the tail-flick latency in the
      absence of minocycline. It can be concluded that the amygdala has a key role in
      the potentiative effect of minocycline on morphine analgesia. In addition,
      amygdala opioidergic and glutamatergic mechanisms may be involved, probably
      through MU-opioid and NMDA receptors, in the modulation of the minocycline
      induced potentiation of morphine analgesia in the tail-flick test. 

PMID- 25563204
TI  - Degradation of pharmaceuticals from membrane biological reactor sludge with
      Trametes versicolor.
AB  - Emerging contaminants are a wide group of chemical products that are found at low
      concentrations in the environment. These contaminants can be either natural,
      e.g., estrogens, or synthetics, such as pesticides and pharmaceuticals, which can
      enter the environment through the water and sludge from wastewater treatment
      plants (WWTP). The growth of Trametes versicolor on membrane biological reactor
      (MBR) sludge in bioslurry systems at the Erlenmeyer scale was assessed and its
      capacity for removing pharmaceutical and personal care products (PPCPs) was
      evaluated. The ability of the fungus to remove hydrochlorothiazide (HZT) from
      liquid media cultures was initially assessed. Consequently, different bioslurry
      media (complete nutrient, glucose and no-nutrient addition) and conditions
      (sterile and non-sterile) were tested, and the removal of spiked HZT was
      monitored under each condition. The highest spiked HZT removal was assessed under
      non-sterile conditions without nutrient addition (93.2%). Finally, the removal
      assessment of a broad set of pharmaceuticals was performed in non-spiked
      bioslurry. Under non-sterile conditions, the fungus was able to completely
      degrade 12 out of the 28 drugs initially detected in the MBR sludge, achieving an
      overall degradation of 66.9%. Subsequent microbial analysis showed that the
      microbial diversity increased after 15 days of treatment, but there was still
      some T. versicolor in the bioslurry. Results showed that T. versicolor can be
      used to remove PPCPs in bioslurry systems under non-sterile conditions, without
      extra nutrients in the media, and in matrices as complex as an MBR sludge. 

PMID- 25563203
TI  - The effect of soybean isoflavone on the dysregulation of NMDA receptor signaling
      pathway induced by beta-amyloid peptides 1-42 in rats.
AB  - Synaptic damage is the key factor of cognitive impairment. The purpose of this
      study was to understand the effect of soybean isoflavone (SIF) on synaptic damage
      induced by beta-amyloid peptide 1-42 (Abeta1-42) in rats. Adult male Wistar rats
      were randomly divided into control, Abeta1-42, SIF, and SIF + Abeta1-42 (SIF
      pretreatment) groups according to body weight. SIF was treated orally by gavage
      in SIF and SIF + Abeta1-42 groups. After 14 days pretreatment with SIF or
      vehicle, Abeta1-42 was injected into the lateral cerebral ventricle of rats in
      Abeta1-42 and SIF + Abeta1-42 groups using miniosmotic pump. The level of Abeta1
      42 and the expression of N-methyl-D-aspartic-acid receptor (NMDAR) were observed
      by immunohistochemistry. Reverse transcriptase polymerase chain reaction was used
      to detect the mRNA levels of NMDAR, calmodulin (CaM), calcium/CaM-dependent
      protein kinase II (CaMKII), cAMP-response element binding protein (CREB), and
      brain-derived neurotrophic factor (BDNF). The results showed that Abeta1-42 down
      regulated mRNA and protein expression of the NR1 and NR2B subunits of NMDAR, SIF
      pretreatment could reverse these changes. The mRNA expression of CaM, CaMKII,
      CREB, and BDNF were down-regulated by Abeta1-42, but they were all regulated by
      SIF pretreatment. These results suggest that SIF pretreatment could antagonize
      the neuron damage in rats induced by Abeta1-42, and its mechanism might be
      associated with the NMDA receptor and CaM/CaMKII/CREB/BDNF signaling pathway,
      which are the synaptic plasticity-related molecules.

PMID- 25563205
TI  - The potential and conditional benefits of retrieval practice on learning.

PMID- 25563206
TI  - Anti-inflammatory and Anti-nociceptive Actions of Systemically or Locally Treated
      Adipose-Derived Mesenchymal Stem Cells in Experimental Inflammatory Model.
AB  - Cell-based therapies using mesenchymal stem cells provide hopeful results.
      Therefore, in this present study, possible anti-inflammatory and anti-nociceptive
      actions of locally or systemically treated adipose-derived mesenchymal stem cells
      (ADMSCs) investigated in experimental inflammation model. ADMSCs were isolated
      from a male Wistar rat under anesthesia, and then they were cultured and expanded
      for transplantation in all the experimental animals. Effects of intraperitoneal
      or intraplantar ADMSC treatments on the hallmarks of the inflammatory
      nociception, such as hyperalgesia, allodynia, edema, and several biochemical
      parameters were investigated using a well-established carrageenan (CG)-induced
      hindpaw inflammation model in male rats. Both local and systemic ADMSC treatment
      increased the latencies, thresholds, and the development of edema in a time
      dependent manner. In addition, administration of ADMSC suppressed the increased
      level of interleukin (IL)-1beta, IL-6, and nitric oxide (NO), but further
      enhanced that of IL-10. Locally treated ADMSC at inflammatory sites effectively
      suppressed the CG-induced inflammatory responses when compared to the
      intraperitoneal route of administration. Findings suggest that therapeutic
      potential of ADMSC can change depending on its route of administration. Local
      ADMSC treatments may suppress the development of inflammatory-nociception and
      edema by decreasing the production of pro-inflammatory cytokines and NO level and
      increasing the anti-inflammatory cytokine production at inflammatory sites. 

PMID- 25563208
TI  - Chromatin fiber allostery and the epigenetic code.
AB  - The notion of allostery introduced for proteins about fifty years ago has been
      extended since then to DNA allostery, where a locally triggered DNA structural
      transition remotely controls other DNA-binding events. We further extend this
      notion and propose that chromatin fiber allosteric transitions, induced by
      histone-tail covalent modifications, may play a key role in transcriptional
      regulation. We present an integrated scenario articulating allosteric mechanisms
      at different scales: allosteric transitions of the condensed chromatin fiber
      induced by histone-tail acetylation modify the mechanical constraints experienced
      by the embedded DNA, thus possibly controlling DNA-binding of allosteric
      transcription factors or further allosteric mechanisms at the linker DNA level.
      At a higher scale, different epigenetic constraints delineate different
      statistically dominant subsets of accessible chromatin fiber conformations, which
      each favors the assembly of dedicated regulatory complexes, as detailed on the
      emblematic example of the mouse Igf2-H19 gene locus and its parental imprinting.
      This physical view offers a mechanistic and spatially structured explanation of
      the observed correlation between transcriptional activity and histone
      modifications. The evolutionary origin of allosteric control supports to speak of
      an 'epigenetic code', by which events involved in transcriptional regulation are
      encoded in histone modifications in a context-dependent way. 

PMID- 25563207
TI  - Additive Suppression of LPS-Induced IL-10 and TNF-alpha by Pre-treatment of
      Dexamethasone and SB203580 in a Murine Alveolar Macrophage Cell Line (MH-S).
AB  - P38 inhibitors are potent anti-inflammatory agents with distinctive mechanism of
      action from corticosteroid; the potential combined use of both anti-inflammatory
      agents could be an effective treatment for inflammatory lung disease; however,
      the impact of such combination on the homeostasis of immune response was poorly
      understood. To investigate the combined effect of dexamethasone (DEX) and/or
      SB203580 on tumor necrosis factor (TNF)-alpha (pro-inflammatory) and interleukin
      (IL)-10 (anti-inflammatory) secretion in mouse alveolar macrophage cell line.
      Secreted TNF-alpha and IL-10 were measured by ELISA. Phosphorylated STAT3 were
      investigated using Western blotting and immunocytochemistry. Pre-treatment of DEX
      or SB203580 inhibited lipopolysaccharide (LPS)-stimulated IL-10, TNF-alpha
      secretion, and STAT3 phosphorylation. Combined use of both agents showed stronger
      inhibitory effect. Combining DEX and SB203580 showed strong inhibition on the LPS
      induced IL-10 secretion and STAT3 phosphorylation, which might reflect a very
      important drawback from the combined use of both anti-inflammatory agents. 

PMID- 25563209
TI  - Relative incidence of phlebitis associated with peripheral intravenous catheters
      in the lower versus upper extremities.
AB  - Peripheral venous access in elderly, hospitalized patients is often challenging.
      The usual alternative is insertion of a central venous catheter, with associated
      risk for complications. The purpose of this investigation was to determine the
      relative incidence of phlebitis secondary to lower as compared to upper extremity
      intravenous catheters (IVCs) and associated risk factors. A non-randomized,
      observational, cohort-controlled study was carried out. Consecutive patients
      receiving a lower extremity IVC were enrolled and compared with patients
      receiving an upper extremity IVC. Patients were followed from insertion until
      removal of the IVC. The major endpoint was phlebitis. The incidence of phlebitis
      secondary to upper extremity IVCs was 3/50 (6 %) compared to 5/53 (9.4 %) in
      lower extremity IVCs (chi(2) Yates = 0.08, p = 0.776). Age, gender, obesity,
      diabetes mellitus, site (arm versus leg, left versus right), and size of needle
      were not found to be risk factors for phlebitis according to univariate analysis.
      None of the patients developed bloodstream infection. In elderly patients with
      poor venous access, lower extremity IVCs are a reasonable and low-risk
      alternative to central venous catheters. 

PMID- 25563211
TI  - Evidence of multiband superconductivity in the beta-phase Mo1-xRex alloys.
AB  - We present a detailed study of the superconducting properties in the beta-phase
      Mo(1-x)Re(x) (x = 0.25 and 0.4) solid solution alloys pursued through
      magnetization and heat capacity measurements. The temperature dependence of the
      upper critical field H(C2)(T) in these binary alloys shows a deviation from the
      prediction of the Werthamer-Helfand-Hohenberg (WHH) theory. The temperature
      dependence of superfluid density estimated from the variation of lower critical
      field H(C1) with temperature, cannot be explained within the framework of a
      single superconducting energy gap. The heat capacity also shows an anomalous
      feature in its temperature dependence. All these results can be reasonably
      explained by considering the existence of two superconducting energy gaps in
      these Mo(1-x)Re(x) alloys. Initial results of electronic structure calculations
      and resonant photoelectron spectroscopy measurements support this possibility and
      suggest that the Re-5d like states at the Fermi level may not intermix with the
      Mo-5p and 5s like states in the beta-phase Mo(1-x)Re(x) alloys and contribute
      quite distinctly to the superconductivity of these alloys.

PMID- 25563210
TI  - Validation of the adult attention-deficit/hyperactivity disorder quality-of-life
      scale in European patients: comparison with patients from the USA.
AB  - The adult attention-deficit/hyperactivity disorder (ADHD) quality-of-life (AAQoL)
      scale was previously validated in adult patients in the USA; here, the AAQoL is
      validated in adult European patients. Data from a 12-week open-label acute
      treatment period with atomoxetine (80-100 mg/day) in adults with ADHD were used.
      Patients (>= 18 to <= 50 years old) had a score >= 2 on >= 6 items on the
      inattentive or hyperactive core subscales of Conners' Adult ADHD Rating Scale
      Investigator Rated: Screening Version (CAARS-Inv:SV); a CAARS-Inv:SV 18-item
      total ADHD symptom score >= 20; and Conners' Adult ADHD Rating Scale-Observer:
      Screening Version 6-item inattentive or hyperactive core subscale scores >= 2.
      Data were stratified based on patients' geographic region (Europe vs USA). Scale
      validation psychometric properties results were very similar between European (n
      = 1,217; 57.7 % male; mean age 33.0 years) and US (n = 602; 62.1 % male; mean age
      33.5 years) patients, including factor loading, internal consistency, convergent
      and discriminant validity, and responsiveness. Exploratory factor analysis
      confirmed four AAQoL subscales. Internal consistency was acceptable (Cronbach's
      alpha > 0.70 for all subscales). The AAQoL total score showed moderate convergent
      validity with CAARS-Inv:SV 18-item total ADHD symptom and clinical global
      impression-ADHD-severity (CGI-ADHD-S) scores; and strong convergent validity with
      Behavior Rating Inventory of Executive Function-Adult Version: Self-Report Global
      Executive-Composite Index scores. Mean AAQoL total scores were significantly
      different among patients grouped by CGI-ADHD-S scores, suggesting good
      discriminant validity. The AAQoL total and subscale scores presented good
      responsiveness from baseline to 12 weeks. The AAQoL scale shows comparable
      validity in European and US adults with ADHD.

PMID- 25563212
TI  - Benzosulfones as photochemically activated sulfur dioxide (SO2) donors.
AB  - Sulfur dioxide (SO2) is a gaseous environmental pollutant which is routinely used
      in industry as a preservative and antimicrobial. Recent data suggests that SO2
      may have value as a therapeutic agent. However, due to its gaseous nature,
      localizing SO2 generation is challenging. Herein, various 1,3
      dihydrobenzo[c]thiophene 2,2-dioxides (benzosulfones) were prepared as candidates
      for photochemically activated sulfur dioxide (SO2) generation. These compounds
      were found to be stable in buffer but were photolysed upon irradiation with UV
      light to generate SO2. Our data indicates that photolysis of benzosulfones
      depends on substituents, and that the presence of electron donating groups
      results in an enhanced yield of SO2. 

PMID- 25563213
TI  - Charge transfer tuning by chemical substitution and uniaxial pressure in the
      organic complex tetramethoxypyrene-tetracyanoquinodimethane.
AB  - In the search for novel organic charge transfer salts with variable degrees of
      charge transfer we have studied the effects of two modifications of the recently
      synthesized donor-acceptor system [tetramethoxypyrene (TMP)]
      [tetracyanoquinodimethane (TCNQ)]. One is of chemical nature by substituting the
      acceptor TCNQ molecules by F4TCNQ molecules. The second consists in simulating
      the application of uniaxial pressure along the stacking axis of the system. In
      order to test the chemical substitution, we have grown single crystals of the TMP
      F4TCNQ complex and analyzed its electronic structure via electronic transport
      measurements, ab initio density functional theory (DFT) calculations and
      UV/VIS/IR absorption spectroscopy. This system shows an almost ideal geometrical
      overlap of nearly planar molecules stacked alternately (mixed stack) and this
      arrangement is echoed by a semiconductor-like transport behavior with an
      increased conductivity along the stacking direction. This is in contrast to TMP
      TCNQ which shows a less pronounced anisotropy and a smaller conductivity
      response. Our band structure calculations confirm the one-dimensional behavior of
      TMP-F4TCNQ with pronounced dispersion only along the stacking axis. Infrared
      measurements illustrating the C=N vibration frequency shift in F4TCNQ suggest
      however no improvement in the degree of charge transfer in TMP-F4TCNQ with
      respect to TMP-TCNQ. In both complexes about 0.1e is transferred from TMP to the
      acceptor. Concerning the pressure effect, our DFT calculations on the designed
      TMP-TCNQ and TMP-F4TCNQ structures under different pressure conditions show that
      application of uniaxial pressure along the stacking axis of TMP-TCNQ may be the
      route to follow in order to obtain a much more pronounced charge transfer.

PMID- 25563214
TI  - High-temperature and high-resolution crystallography of thermostable copper
      nitrite reductase.
AB  - The 1.55 A resolution thermostable copper nitrite reductase structure at 320 K
      displayed a near-bidentate binding mode of nitrite distinct from a monodentate
      mode in a cryogenic structure. To our knowledge, this is the first case in which
      the difference in substrate binding modes between cryogenic and high-temperature
      structures has been visualized by crystallography. 

PMID- 25563216
TI  - Long-term follow-up of re-sting reactions in children with moderate to severe
      venom hypersensitivity.
AB  - Few data exists about re-sting reactions and their prognosis in children with
      moderate to severe venom hypersensitivity. The reasons behind not consenting to
      or prematurely ending venom immunotherapy (VIT) and the preparedness of children
      who refused or quit VIT for future moderate-severe systemic reaction (SR) to re
      stings have not been studied. Data on children with moderate to severe SR after
      Hymenoptera stings was collected for a 17-year period using our database. A
      standardized questionnaire was administered to patients who accepted to be
      interviewed at the clinic. These patients were evaluated in terms of their
      preparedness for future moderate-severe SR to re-stings. A total of 55 children,
      75 % of whom commenced on VIT, were included in the analysis. Different reasons
      exist for not consenting to VIT; the most common of which is living at a distance
      from the allergy center. There were no differences in terms of the number of re
      stung patients (27.7 and 27.2 %, respectively) and moderate-severe SR (60 and
      16.6 %, respectively) between children who prematurely ended or who did not
      consent to VIT and children who completed VIT. Sixty-four percent of the children
      who refused or discontinued VIT were not prepared for future moderate-severe SR
      to re-stings. CONCLUSION: Long-term prognosis for re-sting reactions is good in
      children with moderate to severe SR to venoms. Some of the reasons behind
      refusing or discontinuing VIT may be related to quality of life issues.
      Preparedness of children who refused or discontinue VIT in emergencies is very
      low.

PMID- 25563217
TI  - Determining the persistence of maternally acquired antibodies to hepatitis A and
      varicella zoster during the first 2 years of life in Turkey.
AB  - Vaccination should be timed to take into account the potential interference of
      maternal antibodies. The purpose of this study was to determine the persistence
      of maternally acquired antibodies to hepatitis A and varicella zoster in a group
      of healthy infants between 6 and 24 months of age. These infants were divided
      into four groups according to the age at the time of follow-up visits. The study
      group consisted of infants who were brought to the 6-month follow-up visit (group
      1, n=100), 12-month follow-up visit (group 2, n=99), 18-month follow-up visit
      (group 3, n=59), and 24-month follow-up visit (group 4, n=59). Hepatitis A,
      varicella IgG, and IgM antibodies were analyzed qualitatively. Hepatitis A IgG
      seropositivity was determined as 71 % in group 1, 41.4 % in group 2, 0 % in group
      3, and 8.5 % in group 4 (p<0.001). Varicella IgG seropositivity was found to be 5
      % in group 1, 4 % in group 2, 4 % in group 3, and 1 % in group 4 (p>0.05).
      CONCLUSION: We found that maternal hepatitis A antibodies in children disappear
      between 12 and 18 months, whereas maternal varicella antibodies substantially
      diminish following the sixth month. Therefore, the vaccination timing should be
      based on factors such as the interference of maternal antibodies, disease
      susceptibility period, and immune maturation.

PMID- 25563218
TI  - A long-term, prospective, cohort study on the performance of right ventricular
      pacing leads: comparison of active-fixation with passive-fixation leads.
AB  - Active-fixation pacing leads allow the use of selective pacing sites. We
      evaluated their long-term performance versus passive-fixation leads in 199 newly
      implanted patients (n = 100 active and n = 99 passive). Postoperative pacing
      thresholds in the active group were higher than in the passive group (0.85 +/-
      0.31 V vs. 0.53 +/- 0.21 V at baseline, P < 0.001). The active thresholds fell to
      0.72 +/- 0.23 V at 5 years with a significant drop at one month (0.68 +/- 0.53 V,
      P = 0.003). The passive thresholds slightly increased to 0.72 +/- 0.31 V at five
      years. Differences between groups were significant until three years (all P <
      0.05). Active impedances were generally lower than passive impedances (600.44 +/-
      94.31Omega vs. 683.14 +/- 110.98Omega at baseline), and both showed significant
      reductions at one month to 537.96 +/- 147.43Omega in the active group, and after
      three months to 643.85 +/- 82.40Omega in the passive group (both P < 0.01 vs.
      baseline). Impedance differences between groups were significant until four years
      (all P < 0.05). Adverse events included thresholds over 1 V, 5 of 6 active and 2
      of 5 passive leads returned to below 1 V. One active left ventricular lead
      dislodged. One passive left subclavian lead insulation fracture occurred. Thus
      Active fixation pacing leads are stable in a five-year long-term follow up. There
      was no difference between active and passive leads in terms of electrical
      performance.

PMID- 25563219
TI  - Formative evaluation of clinician experience with integrating family history
      based clinical decision support into clinical practice.
AB  - Family health history is a leading predictor of disease risk. Nonetheless, it is
      underutilized to guide care and, therefore, is ripe for health information
      technology intervention. To fill the family health history practice gap,
      Cleveland Clinic has developed a family health history collection and clinical
      decision support tool, MyFamily. This report describes the impact and process of
      implementing MyFamily into primary care, cancer survivorship and cancer genetics
      clinics. Ten providers participated in semi-structured interviews that were
      analyzed to identify opportunities for process improvement. Participants
      universally noted positive effects on patient care, including increases in
      quality, personalization of care and patient engagement. The impact on clinical
      workflow varied by practice setting, with differences observed in the ease of
      integration and the use of specific report elements. Tension between the length
      of the report and desired detail was appreciated. Barriers and facilitators to
      the process of implementation were noted, dominated by the theme of increased
      integration with the electronic medical record. These results fed real-time
      improvement cycles to reinforce clinician use. This model will be applied in
      future institutional efforts to integrate clinical genomic applications into
      practice and may be useful for other institutions considering the implementation
      of tools for personalizing medical management. 

PMID- 25563215
TI  - The intestinal microbiota: its role in health and disease.
AB  - The intestinal microbiota (previously referred to as "intestinal flora") has
      entered the focus of research interest not only in microbiology but also in
      medicine. Huge progress has been made with respect to the analysis of composition
      and functions of the human microbiota. An "imbalance" of the microbiota,
      frequently also called a "dysbiosis," has been associated with different diseases
      in recent years. Crohn's disease and ulcerative colitis as two major forms of
      inflammatory bowel disease, irritable bowel syndrome (IBS) and some infectious
      intestinal diseases such as Clostridium difficile colitis feature a dysbiosis of
      the intestinal flora. Whereas this is somehow expected or less surprising, an
      imbalance of the microbiota or an enrichment of specific bacterial strains in the
      flora has been associated with an increasing number of other diseases such as
      diabetes, metabolic syndrome, non-alcoholic fatty liver disease or
      steatohepatitis and even psychiatric disorders such as depression or multiple
      sclerosis. It is important to understand the different aspects of potential
      contributions of the microbiota to pathophysiology of the mentioned diseases.
      CONCLUSION: With the present manuscript, we aim to summarize the current
      knowledge and provide an overview of the different concepts on how bacteria
      contribute to health and disease in animal models and-more importantly-humans. In
      addition, it has to be borne in mind that we are only at the very beginning to
      understand the complex mechanisms of host-microbial interactions.

PMID- 25563220
TI  - Ethics, evidence and economics in the pursuit of "personalized medicine".
AB  - Despite enthusiastic advocacy for what personalized medicine might be able to
      deliver and major investments into the development of this, there remain
      disappointingly few examples of personalized medicine in routine clinical
      practice today, particularly in high areas of unmet need such as cancer. We
      believe that this is because personalized medicine challenges the moral, economic
      and epistemological foundations of medicine. In this article, we briefly describe
      the scientific premises underpinning personalized medicine, contrast these with
      traditional paradigms of drug development, and then consider the ethical,
      economic and epistemological implications of this approach to medicine. 

PMID- 25563222
TI  - Personalized Medicine's Bottleneck: Diagnostic Test Evidence and Reimbursement.
AB  - BACKGROUND: Personalized medicine is gradually emerging as a transformative
      field. Thus far, seven co-developed drug-diagnostic combinations have been
      approved and several dozen post-hoc drug-diagnostic combinations (diagnostic
      approved after the drug). However, barriers remain, particularly with respect to
      reimbursement. Purpose, methods: This study analyzes barriers facing uptake of
      drug-diagnostic combinations. We examine Medicare reimbursement in the U.S. of 10
      drug-diagnostic combinations on the basis of a formulary review and a survey.
      FINDINGS: We found that payers reimburse all 10 drugs, but with variable and
      relatively high patient co-insurance, as well as imposition of formulary
      restrictions. Payer reimbursement of companion diagnostics is limited and highly
      variable. In addition, we found that the body of evidence on the clinical- and
      cost-effectiveness of therapeutics is thin and even less robust for diagnostics.
      Conclusions, discussion: The high cost of personalized therapeutics and dearth of
      evidence concerning the comparative clinical effectiveness of drug-diagnostic
      combinations appear to contribute to high patient cost sharing, imposition of
      formulary restrictions, and limited and variable reimbursement of companion
      diagnostics. Our findings point to the need to increase the evidence base
      supportive of establishing linkage between diagnostic testing and positive health
      outcomes.

PMID- 25563221
TI  - Genetically guided statin therapy on statin perceptions, adherence, and
      cholesterol lowering: a pilot implementation study in primary care patients.
AB  - Statin adherence is often limited by side effects. The SLCO1B1*5 variant is a
      risk factor for statin side effects and exhibits statin-specific effects: highest
      with simvastatin/atorvastatin and lowest with pravastatin/rosuvastatin. The
      effects of SLCO1B1*5 genotype guided statin therapy (GGST) are unknown. Primary
      care patients (n = 58) who were nonadherent to statins and their providers
      received SLCO1B1*5 genotyping and guided recommendations via the electronic
      medical record (EMR). The primary outcome was the change in Beliefs about
      Medications Questionnaire, which measured patients' perceived needs for statins
      and concerns about adverse effects, measured before and after SLCO1B1*5 results.
      Concurrent controls (n = 59) were identified through the EMR to compare secondary
      outcomes: new statin prescriptions, statin utilization, and change in LDL
      cholesterol (LDL-c). GGST patients had trends (p = 0.2) towards improved statin
      necessity and concerns. The largest changes were the "need for statin to prevent
      sickness" (p < 0.001) and "concern for statin to disrupt life" (p = 0.006). GGST
      patients had more statin prescriptions (p < 0.001), higher statin use (p <
      0.001), and greater decrease in LDL-c (p = 0.059) during follow-up. EMR delivery
      of SLCO1B1*5 results and recommendations is feasible in the primary care setting.
      This novel intervention may improve patients' perceptions of statins and
      physician behaviors that promote higher statin adherence and lower LDL-c. 

PMID- 25563223
TI  - Impact of information technology on the therapy of type-1 diabetes: a case study
      of children and adolescents in Germany.
AB  - Being able to manage and adjust insulin doses is a key part of managing type-1
      diabetes. Children and adolescents with type-1 diabetes mellitus often have
      serious difficulties with this dosage adjustment. Therefore, this paper aims to
      investigate the impact of using novel mobile, web and communication technologies
      in assisting their therapy and treatment. A trial was conducted in the north
      eastern part of Germany to evaluate the impact of the "Mobil Diab", a mobile
      diabetes management system, on the clinical outcome. 68 subjects aged between 8
      and 18 years, divided randomly into control and intervention groups, were
      included into the study. Metrics such as changes in the quality of metabolic
      control, changes in psychological parameters, usability and acceptance of the
      technology were used for evaluation purpose. Metabolic control was mainly
      assessed by the mean HbAlc. Analysis showed a good acceptance of the proposed
      system. An overall improvement in mean levels of HbA1c was observed, however
      further studies will be conducted to prove evidence of the weight and BMI
      improvements. Moreover, initial indications of positive impact on the improvement
      in psychological parameters were presumed based on the result of the conducted
      study. The system appeared to be an efficient and time saving tool in diabetes
      management. 

PMID- 25563224
TI  - Knowledge, attitudes and referral patterns of lynch syndrome: a survey of
      clinicians in australia.
AB  - This study assessed Australian clinicians' knowledge, attitudes and referral
      patterns of patients with suspected Lynch syndrome for genetic services. A total
      of 144 oncologists, surgeons, gynaecologists, general practitioners and
      gastroenterologists from the Australian Medical Association and Clinical Oncology
      Society responded to a web-based survey. Most respondents demonstrated suboptimal
      knowledge of Lynch syndrome. Male general practitioners who have been practicing
      for >=10 years were less likely to offer genetic referral than specialists, and
      many clinicians did not recognize that immunohistochemistry testing is not a
      germline test. Half of all general practitioners did not actually refer patients
      in the past 12 months, and 30% of them did not feel that their role is to
      identify patients for genetic referral. The majority of clinicians considered
      everyone to be responsible for making the initial referral to genetic services,
      but a small preference was given to oncologists (15%) and general practitioners
      (13%). Patient information brochures, continuing genetic education programs and
      referral guidelines were favoured as support for practice. Targeted education
      interventions should be considered to improve referral. An online family history
      assessment tool with built-in decision support would be helpful in triaging high
      risk individuals for pathology analysis and/or genetic assessment in general
      practice. 

PMID- 25563225
TI  - Human centred design considerations for connected health devices for the older
      adult.
AB  - Connected health devices are generally designed for unsupervised use, by non
      healthcare professionals, facilitating independent control of the individuals own
      healthcare. Older adults are major users of such devices and are a population
      significantly increasing in size. This group presents challenges due to the wide
      spectrum of capabilities and attitudes towards technology. The fit between
      capabilities of the user and demands of the device can be optimised in a process
      called Human Centred Design. Here we review examples of some connected health
      devices chosen by random selection, assess older adult known capabilities and
      attitudes and finally make analytical recommendations for design approaches and
      design specifications. 

PMID- 25563226
TI  - Differential transcriptome profile of peripheral white cells to identify
      biomarkers involved in oxaliplatin induced neuropathy.
AB  - Anticancer chemotherapy (CT) produces non-desirable effects on normal healthy
      cells and tissues. Oxaliplatin is widely used in the treatment of colorectal
      cancer and responsible for the development of sensory neuropathy in varying
      degrees, from complete tolerance to chronic neuropathic symptoms. We studied the
      differential gene expression of peripheral leukocytes in patients receiving
      oxaliplatin-based chemotherapy to find genes and pathways involved in oxaliplatin
      induced peripheral neuropathy. Circulating white cells were obtained prior and
      after three cycles of FOLFOX or CAPOX chemotherapy from two groups of patients:
      with or without neuropathy. RNA was purified, and transcriptomes were analyzed.
      Differential transcriptomics revealed a total of 502 genes, which were
      significantly up- or down-regulated as a result of chemotherapy treatment. Nine
      of those genes were expressed in only one of two situations: CSHL1, GH1, KCMF1,
      IL36G and EFCAB8 turned off after CT, and CSRP2, IQGAP1, GNRH2, SMIM1 and C5orf17
      turned on after CT. These genes are likely to be associated with the onset of
      oxaliplatin-induced peripheral neuropathy. The quantification of their expression
      in peripheral white cells may help to predict non-desirable side effects and,
      consequently, allow a better, more personalized chemotherapy. 

PMID- 25563228
TI  - Errors on interrupter tasks presented during spatial and verbal working memory
      performance are linearly linked to large-scale functional network connectivity in
      high temporal resolution resting state fMRI.
AB  - The brain is organized into networks composed of spatially separated anatomical
      regions exhibiting coherent functional activity over time. Two of these networks
      (the default mode network, DMN, and the task positive network, TPN) have been
      implicated in the performance of a number of cognitive tasks. To directly examine
      the stable relationship between network connectivity and behavioral performance,
      high temporal resolution functional magnetic resonance imaging (fMRI) data were
      collected during the resting state, and behavioral data were collected from 15
      subjects on different days, exploring verbal working memory, spatial working
      memory, and fluid intelligence. Sustained attention performance was also
      evaluated in a task interleaved between resting state scans. Functional
      connectivity within and between the DMN and TPN was related to performance on
      these tasks. Decreased TPN resting state connectivity was found to significantly
      correlate with fewer errors on an interrupter task presented during a spatial
      working memory paradigm and decreased DMN/TPN anti-correlation was significantly
      correlated with fewer errors on an interrupter task presented during a verbal
      working memory paradigm. A trend for increased DMN resting state connectivity to
      correlate to measures of fluid intelligence was also observed. These results
      provide additional evidence of the relationship between resting state networks
      and behavioral performance, and show that such results can be observed with high
      temporal resolution fMRI. Because cognitive scores and functional connectivity
      were collected on nonconsecutive days, these results highlight the stability of
      functional connectivity/cognitive performance coupling. 

PMID- 25563229
TI  - Meta-analyses of structural regional cerebral effects in type 1 and type 2
      diabetes.
AB  - Diabetes is associated with macrovascular and microvascular complications and is
      a major risk factor for neurological and psychiatric disorders, such as dementia
      and depression. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) have distinct
      etiologies and pathophysiological effects while sharing a common endpoint of
      persistent hyperglycemia. Neuroimaging studies in T1DM have revealed reductions
      in numerous regions, including the parahippocampal and occipital regions, while
      in T2DM there have been numerous reports of hippocampal atrophy. This meta
      analysis aimed to identify consistent regional abnormalities in cerebral
      structures in T1DM and T2DM respectively, and also to examine the impact of
      potential confounds, including age, depression and vascular risk factors.
      Neuroimaging studies of both voxel-based morphometry (VBM) data and volumetric
      data were included. Ten T1DM studies (n = 613 patients) and 23 T2DM studies (n =
      1364 patients) fulfilled inclusion criteria. The T1DM meta-analysis revealed
      reduced bilateral thalamus grey matter density in adults. The T2DM meta-analysis
      revealed reduced global brain volume and regional atrophy in the hippocampi,
      basal ganglia, and orbitofrontal and occipital lobes. Moreover, hippocampal
      atrophy in T2DM was not modified by hypertension, although there were more marked
      reductions in younger patients relative to healthy controls. In conclusion, T1DM
      and T2DM demonstrated distinct cerebral effects with generalised and specific
      target areas of grey matter reduction. Thalamic atrophy in T1DM may be a
      substrate of associated cognitive deficits. In T2DM, global cerebral atrophy may
      reflect atherosclerotic factors, while hippocampal atrophy was an independent
      effect providing a potential common neuropathological etiology for the
      comorbidity of T2DM with dementia and depression. 

PMID- 25563227
TI  - Physiologic artifacts in resting state oscillations in young children:
      methodological considerations for noisy data.
AB  - We quantified the potential effects of physiologic artifact on the estimation of
      EEG band power in a cohort of typically developing children in order to guide
      artifact rejection methods in quantitative EEG data analysis in developmental
      populations. High density EEG was recorded for 2 min while children, ages 2-6,
      watched a video of bubbles. Segments of data were categorized as blinks,
      saccades, EMG or artifact-free, and both absolute and relative power in the theta
      (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz) and gamma (35-45 Hz) bands were
      calculated in 9 regions for each category. Using a linear mixed model approach
      with artifact type, region and their interaction as predictors, we compared mean
      band power between clean data and each type of artifact. We found significant
      differences in mean relative and absolute power between artifacts and artifact
      free segments in all frequency bands. The magnitude and direction of the
      differences varied based on power type, region, and frequency band. The most
      significant differences in mean band power were found in the gamma band for EMG
      artifact and the theta band for ocular artifacts. Artifact detection strategies
      need to be sensitive to the oscillations of interest for a given analysis, with
      the most conservative approach being the removal of all EMG and ocular artifact
      from EEG data. Quantitative EEG holds considerable promise as a clinical
      biomarker of both typical and atypical development. However, there needs to be
      transparency in the choice of power type, regions of interest, and frequency
      band, as each of these variables are differentially vulnerable to noise, and
      therefore, their interpretation depends on the methods used to identify and
      remove artifacts. 

PMID- 25563230
TI  - Effects of methylphenidate during emotional processing in amphetamine users:
      preliminary findings.
AB  - D-amphetamine (dAMPH) and methylphenidate (MPH) are stimulants used in the
      treatment of Attention Deficit Hyperactivity Disorder (ADHD). Preclinical studies
      have shown that in healthy animals, dAMPH induces dopamine (DA) dysfunction, as
      evidenced for instance by loss of DA levels and its transporters. It has also
      been suggested that DA plays an important role in emotional processing, and that
      altered DA-ergic intervention may modulate amygdala function. To explore the role
      of the DA system in emotional processing we examined emotional processing using
      functional magnetic resonance imaging (fMRI) in eight male recreational users of
      dAMPH and eight male healthy controls. We compared brain activation between both
      groups during an emotional face-processing task with and without an oral MPH
      challenge. All subjects were abstinent for at least 2 weeks during the baseline
      scan. The second scan was performed on the same day 11/2 hours after receiving an
      oral dose of 35 mg MPH. A significant Valence*Group interaction (p = .037)
      indicated amygdala hyperreactivity to fearful facial expressions in dAMPH users
      that was robust against adjustment for age (p = .015). Furthermore, duration of
      amphetamine use in years was positively correlated with amygdala reactivity in
      dAMPH users (r = .76; p = .029). These exploratory findings are in line with
      previous findings suggesting that DA plays a role in emotional processing.

PMID- 25563231
TI  - Clinicopathological and outcome analysis of adult lupus nephritis patients in
      China.
AB  - BACKGROUND: The objective of this study was to assess clinicopathological
      characteristics and outcomes of lupus nephritis adult patients in China. METHODS:
      Clinicopathological features, treatment strategies, responses and outcome of 681
      adult patients with biopsy-proved lupus nephritis were retrospectively analyzed.
      RESULTS: Six hundred and eighty-one LN patients were included and followed up for
      52.5 +/- 14.1 months. Differences in age, disease duration, BP, proteinuria,
      serum albumin, creatinine, ANCA-positive ratio and SLEDAI scores were noticed
      between male and female patients, indicating severer disease in male patients. LN
      IV patients were much severer in systemic damage as well as immunological
      changes. During follow-up, 354 patients achieved CR, 107 patients achieved PR, 95
      patients progressed to ESRD and 36 patients died. Prognosis and treatment
      response of patients with different histological types differ apparently. Renal
      outcome of patients with LN II and III was benign, while LN IV, V and VI was
      poor. Cyclophosphamide was effective in most patients. MMF and CNI could be used
      as salvage treatment. In multivariate analysis, BP, sCr, hypocomplementemia,
      severe proliferative lesion (LN IV or VI) and SLEDAI score were recognized as
      independent indicators of poor renal outcome. Infections, especially pulmonary
      fungus infection, thrombotic microangiopathy are the most common causes of death
      in LN patients. CONCLUSIONS: Clinicopathological characteristics, treatment
      responses and long-term outcomes differ remarkably in LN patients with different
      gender and pathological subtypes. New indicators of poor renal outcome were
      identified. Infections and TTP were the most common causes of death in LN
      patients.

PMID- 25563232
TI  - Does the presence of hydronephrosis have effects on micropercutaneous
      nephrolithotomy?
AB  - PURPOSE: To evaluate the effects of presence of hydronephrosis on
      micropercutaneous nephrolithotomy (micro-PNL) surgery. PATIENTS AND METHODS: A
      retrospective analysis of 112 patients who underwent microperc surgery between
      December 2012 and April 2014 was performed. Patients were evaluated in two groups
      according to whether the presence of hydronephrosis. Stone size and location,
      fluoroscopy and operation time, stone-free rates and patient-related parameters
      were prospectively recorded into a centralized computer-generated system.
      RESULTS: A total of 58 patients in Group 1 with hydronephrosis and 54 patients in
      Group 2 with no hydronephrosis were analyzed. There was no statistically
      significant difference in terms of stone sizes and body mass indexes (BMI) in
      comparison of groups (155.2 +/- 93.06 vs. 143.70 +/- 70.77 mm(2), p = 0.856 and
      27.6 +/- 4.2 vs. 26.7 +/- 3.2 kg/m(2), p = 0.625). The success rates were similar
      (91.3 vs. 92.5%, p = 0.341). While the mean operation time and fluoroscopy time
      in Group 1 were 44.2 +/- 23.62 min and 105.3 +/- 47 s, it was 38.8 +/- 26.4 min
      and 112.53 +/- 68.3 s in Group 2, but there was no statistical difference in
      comparison of both groups. The mean attempts of percutan puncture were 1.35 +/-
      0.47 in Group 1 and 1.76 +/- 0.31 in Group 2 (p = 0.185). We also found no
      statistical differences regarding mean hemoglobin change and hospitalization
      time, respectively (p = 0.685 and p = 0753). In comparison of grades of
      hydronephrosis, there was no statistically significant difference in subgroups
      analysis. CONCLUSIONS: The presence of hydronephrosis does not affect success
      rates and operative time in micro-PNL procedures significantly. Micropercutaneous
      nephrolithotomy is technically feasible and efficacious both in hydronephrotic
      and non-hydronephrotic kidneys.

PMID- 25563234
TI  - Excellent catalytic effects of multi-walled carbon nanotube supported titania on
      hydrogen storage of a Mg-Ni alloy.
AB  - Superior catalytic effects of multi-walled carbon nanotube supported titania
      synthesized by the sol-gel method on hydrogen storage of a Mg-Ni alloy were
      investigated. The excellent hydrogen storage properties were obtained: absorbed
      5.60 wt% H2 within 60 s at 373 K and released 6.08 wt% H2 within 600 s at 553 K. 

PMID- 25563233
TI  - Prospective Effects of Family Cohesion on Alcohol-Related Problems in
      Adolescence: Similarities and Differences by Race/Ethnicity.
AB  - Research increasingly finds that race/ethnicity needs to be taken into account in
      the modelling of associations between protective factors and adolescent drinking
      behaviors in order to understand family effects and promote positive youth
      development. The current study examined racial/ethnic variation in the
      prospective effects of family cohesion on adolescent alcohol-related problems
      using a nationally representative sample. Data were drawn from the first two
      waves of the National Longitudinal Study of Adolescent to Adult Health and
      included 10,992 (50% female) non-Hispanic Asian, non-Hispanic Black, Latino, and
      non-Hispanic White 7th-12th graders. Consistent with Hirschi's social control
      theory of youth delinquency, higher levels of family cohesion predicted lower
      levels of future adolescent alcohol-related problems, independent of
      race/ethnicity, sex, age, baseline alcohol-related problems, and family
      socioeconomic status. Findings from moderation analyses indicated that the
      magnitude of associations differed across groups such that the protective effect
      of family cohesion was strongest among White adolescents. For Latino adolescents,
      family cohesion was not associated with alcohol-related problems. Future
      longitudinal cross-racial/ethnic research is needed on common and unique
      mechanisms underlying differential associations between family processes and
      adolescent high-risk drinking. Understanding these processes could help improve
      preventive interventions, identify vulnerable subgroups, and inform health policy
      aimed at reducing alcohol-related health disparities.

PMID- 25563235
TI  - Monetary discounting and ventral striatal dopamine receptor availability in
      nontreatment-seeking alcoholics and social drinkers.
AB  - RATIONALE: Dopamine (DA) in the ventral striatum (VST) has long been implicated
      in addiction pathologies, yet its role in temporal decision-making is not well
      understood. OBJECTIVES: To determine if VST DA D2 receptor availability
      corresponds with greater impulsive choice in both nontreatment-seeking alcoholics
      (NTS) and social drinkers (SD). METHODS: NTS subjects (n = 10) and SD (n = 13)
      received PET scans at baseline with the D2/D3 radioligand [(11)C]raclopride
      (RAC). Outside the scanner, subjects performed a delay discounting procedure with
      monetary rewards. RAC binding potential (BPND) was estimated voxelwise, and
      correlations were performed to test for relationships between VST BPND and delay
      discounting performance. Self-reported impulsivity was also tested for
      correlations with BPND. RESULTS: Across all subjects, greater impulsive choice
      for $20 correlated with lower BPND in the right VST. NTS showed greater impulsive
      choice than SD and were more impulsive by self-report. Across all subjects, the
      capacity of larger rewards to reduce impulsive choice (the magnitude effect)
      correlated negatively (p = 0.028) with problematic alcohol use (AUDIT) scores.
      Self-reported impulsivity did not correlate with BPND in VST. CONCLUSIONS:
      Preference for immediate reinforcement may reflect greater endogenous striatal DA
      or lower D2 number, or both. Alcoholic status did not mediate significant effects
      on VST BPND, suggesting minimal effects from alcohol exposure. The apparent lack
      of BPND correlation with self-reported impulsivity highlights the need for
      objective behavioral assays in the study of the neurochemical substrates of
      behavior. Finally, our results suggest that the magnitude effect may be more
      sensitive to alcohol-induced problems than single discounting measures.

PMID- 25563236
TI  - Effects of diphenyl and p-chloro-diphenyl diselenides on feeding behavior of
      rats.
AB  - RATIONALE: The searching for safe and effective antiobesity drugs has been the
      subject of intense research. Previous studies have shown several pharmacological
      applications of organoselenium compounds; however, their possible anorectic-like
      actions have not been investigated. OBJECTIVE: This study aims to investigate the
      effects of (PhSe)2 and (p-ClPhSe)2 on feeding behavior of rats and their
      potential as weight-reducing agents. METHODS: The effects of intraperitoneal
      administration of diselenides were investigated through the microstructural
      pattern of feeding behavior, behavioral satiety sequence (BSS), hypothalamic
      serotonin (5-HT) uptake, body weight, and epididymal fat content of male rats.
      RESULTS: Our findings demonstrated that food intake of fasted rats was reduced by
      both diselenides (1 and 10 mg/kg). Diphenyl diselenide [(PhSe)2] (1 mg/kg) and p
      chloro-diphenyl diselenide [(p-ClPhSe)2] (10 mg/kg) decreased the frequency, mean
      duration, and mean size of meals compared with the control treatment. The BSS
      structure was preserved when organoselenium compounds (1 mg/kg) were
      administered, and it was associated to a displacement to the left when the
      resting period started indicating a satiating action. Inhibition of 5-HT uptake
      in the hypothalamus (~20 %) was also found in rats treated with low doses of
      (PhSe)2 and (p-ClPhSe)2 (1 mg/kg). Treatments with a high dose of both
      diselenides (10 mg/kg) carried out for 7 days induced weight loss and epididymal
      fat reduction in sated rats. CONCLUSION: This study suggests that diselenides
      caused a satiating action in rats that could be partially explained by the
      inhibition of hypothalamic 5-HT uptake. These organoselenium compounds were
      potential weight-reducing agents when repeatedly administered.

PMID- 25563238
TI  - The effects of hypotensive anaesthesia on otoacoustic emissions: a prospective,
      randomized, double-blind study with objective outcome measures.
AB  - The aim of the present study was to compare pre- and post-operative otoacoustic
      emission examinations of patients who experienced surgery under hypotensive
      anaesthesia using distortion product otoacoustic emission (DPOAE) and transient
      evoked otoacoustic emission (TEOAE). Forty-one patients, admitted to our tertiary
      centre for nasal valve surgery, were prospectively and randomly assigned into two
      groups. Hypotensive group included 20 patients, while control group included 21
      patients. All investigators and patients were blinded to anaesthesia assignment
      throughout the course of the study. DPOAEs and TEOAEs were performed before
      surgery and repeated after 15 days in both groups. In control group, DPOAE-DP1
      levels per frequency increased significantly in the post-operative period when
      compared with the pre-operative values in all patients. However, DPOAE-DP1 levels
      decreased significantly in hypotensive group. Similarly, DPOAE-SNR levels per
      frequency decreased significantly in hypotensive group. In conclusion, we have
      observed that under the influence of hypotensive general anaesthesia, the
      amplitudes of OAEs are affected.

PMID- 25563237
TI  - Structural connectivity of neural reward networks in youth at risk for substance
      use disorders.
AB  - BACKGROUND: Having a positive family history of alcohol use disorders (FHP), as
      well as aberrant reward circuitry, has been implicated in the initiation of
      substance use during adolescence. This study explored the relationship between
      FHP status and reward circuitry in substance naive youth to better understand
      future risky behaviors. METHODS: Participants were 49 FHP and 45 demographically
      matched family history negative (FHN) substance-naive 12-14 year-olds (54 %
      female). Subjects underwent structural magnetic resonance imaging, including
      diffusion tensor imaging. Nucleus accumbens and orbitofrontal cortex volumes were
      derived using FreeSurfer, and FSL probabilistic tractography probed structural
      connectivity and differences in white matter diffusivity estimates (e.g.
      fractional anisotropy, and mean, radial, and axial diffusivity) between fiber
      tracts connecting these regions. RESULT: FHP and FHN youth did not differ on
      nucleus accumbens or orbitofrontal cortex volumes, white matter tract volumes, or
      percentages of streamlines (a proxy for fiber tract count) connecting these
      regions. However, within white matter tracts connecting the nucleus accumbens to
      the orbitofrontal cortex, FHP youth had significantly lower mean and radial
      diffusivity (ps < 0.03) than FHN youth. DISCUSSION: While white matter
      macrostructure between salience and reward regions did not differ between FHP and
      FHN youth, FHP youth showed greater white matter coherence within these tracts
      than FHN youth. Aberrant connectivity between reward regions in FHP youth could
      be linked to an increased risk for substance use initiation.

PMID- 25563239
TI  - The middle ear immune defense changes with age.
AB  - Otitis media is a common disease in childhood. In adults, the disease is
      relatively rare, but more frequently associated with complications. Possible
      reasons for this discrepancy are age-related differences in pathogen exposure,
      anatomy of the Eustachian tube and immune system. The objective of this study was
      to analyze the relationship between age and the mucosal immune system in the
      middle ear. It is hypothesized that genes involved in the middle ear immune
      system will change with age. A comprehensive assessment of these genetic
      differences using the techniques of complementary DNA has not been performed.
      Complementary DNA microarray technology was used to identify immune-related genes
      differentially expressed between the normal middle ear mucosa of young (10 days
      old) and adult rats (80 days old). Data were analyzed using tools of
      bioinformatics. A total of 260 age-related genes were identified, of which 51
      genes were involved in the middle ear mucosal immune system. Genes related to the
      innate immune system, including alpha-defensin, calcium-binding proteins S100A9
      and S100A8, were upregulated in young rats, whereas genes related to the adaptive
      immune system, including CD3 molecules, zeta-chain T-cell receptor-associated
      protein kinase and linker of activated T-cells, were upregulated in the adult.
      This study concludes that the normal middle ear immune system changes with age.
      Genes related to the innate immune system are upregulated in young rats, whereas
      genes related to the adaptive immune system are upregulated in adults.

PMID- 25563240
TI  - Assessing the rhinoplasty outcome: inter-rater variability of aesthetic
      perception in the light of objective facial analysis.
AB  - The aim of this study was to assess the success of rhinoplasty by evaluating the
      inter-rater variability in the light of primary indication as functional or
      cosmetic. Subjective aesthetic perception was compared with objective facial
      analysis. 45 rhinoplasty patients were included in the study. 25 had cosmetic
      plus functional reasons with septal deviation (group 1) and 20 had pure cosmetic
      reasons without septal deviation (group 2). Preoperatively and 6 months
      postoperatively, four individuals (patient, surgeon, 2 independent surgeons)
      rated the aesthetic appearance of the nose with visual analogue scale. Facial
      photogrammetric analysis was applied. The patient's aesthetic perception score
      was significantly correlated with the two independent surgeons (p < 0.05) whereas
      not with the primary surgeons. Regarding the objective parameters, patient's
      aesthetic perception was significantly correlated with the dorsal alignment in
      both groups (p < 0.05). General satisfaction score was significantly correlated
      with the nasal breathing as well as with the aesthetic perception scores in both
      groups. This correlation was higher for aesthetic perception in group 1 and nasal
      breathing in group 2. Inter-rater variability of outcome perception was higher in
      cosmetic patients. Nasal dorsal alignment was the only objective parameter which
      was correlated with the patient's perception. Patient's perception of outcome has
      better represented the objective photogrammetric analysis rather than the primary
      surgeons. An interesting finding was the more significant correlation of general
      satisfaction with aesthetic perception in the functional group whereas nasal
      breathing in the cosmetic group.

PMID- 25563242
TI  - Point/counterpoint. "Hybrid gold" is the most appropriate open-access modality
      for journals like Medical Physics.

PMID- 25563241
TI  - Profiling the circulating miRNAs in mice exposed to gram-positive and gram
      negative bacteria by Illumina small RNA deep sequencing.
AB  - BACKGROUND: We profiled the expression of circulating microRNAs (miRNAs) in mice
      using Illumina small RNA deep sequencing in order to identify the miRNAs that may
      potentially be used as biomarkers to distinguish between gram-negative and gram
      positive bacterial infections. RESULTS: Recombinant-specific gram-negative
      pathogen Escherichia coli (Xen14) and gram-positive pathogen Staphylococcus
      aureus (Xen29) were used to induce bacterial infection in mice at a concentration
      of 1 * 10(8) bacteria/100 MUL of phosphate buffered saline (PBS). Small RNA
      libraries generated from the serum of mice after exposure to PBS, Xen14, Xen29,
      and Xen14 + Xen29 via the routes of subcutaneous injection (I), cut wound (C), or
      under grafted skin (S) were analyzed using an Illumina HiSeq2000 Sequencer.
      Following exposure to gram-negative bacteria alone, no differentially expressed
      miRNA was found in the injection, cut, or skin graft models. Exposure to mixed
      bacteria induced a similar expression pattern of the circulating miRNAs to that
      induced by gram-positive bacterial infection. Upon gram-positive bacterial
      infection, 9 miRNAs (mir-193b-3p, mir-133a-1-3p, mir-133a-2-3p, mir-133a-1-5p,
      mir-133b-3p, mir-434-3p, mir-127-3p, mir-676-3p, mir-215-5p) showed upregulation
      greater than 4-fold with a p-value < 0.01. Among them, mir-193b-3p, mir-133a-1
      3p, and mir-133a-2-3p presented the most common miRNA targets expressed in the
      mice exposed to gram-positive bacterial infection. CONCLUSIONS: This study
      identified mir-193b-3p, mir-133a-1-3p, and mir-133a-2-3p as potential circulating
      miRNAs for gram-positive bacterial infections.

PMID- 25563243
TI  - Monitoring external beam radiotherapy using real-time beam visualization.
AB  - PURPOSE: To characterize the performance of a novel radiation therapy monitoring
      technique that utilizes a flexible scintillating film, common optical detectors,
      and image processing algorithms for real-time beam visualization (RT-BV).
      METHODS: Scintillating films were formed by mixing Gd2O2S:Tb (GOS) with silicone
      and casting the mixture at room temperature. The films were placed in the path of
      therapeutic beams generated by medical linear accelerators (LINAC). The emitted
      light was subsequently captured using a CMOS digital camera. Image processing
      algorithms were used to extract the intensity, shape, and location of the
      radiation field at various beam energies, dose rates, and collimator locations.
      The measurement results were compared with known collimator settings to validate
      the performance of the imaging system. RESULTS: The RT-BV system achieved a
      sufficient contrast-to-noise ratio to enable real-time monitoring of the LINAC
      beam at 20 fps with normal ambient lighting in the LINAC room. The RT-BV system
      successfully identified collimator movements with sub-millimeter resolution.
      CONCLUSIONS: The RT-BV system is capable of localizing radiation therapy beams
      with sub-millimeter precision and tracking beam movement at video-rate exposure.

PMID- 25563245
TI  - Comprehensive MRI simulation methodology using a dedicated MRI scanner in
      radiation oncology for external beam radiation treatment planning.
AB  - PURPOSE: The use of magnetic resonance imaging (MRI) in radiation oncology is
      expanding rapidly, and more clinics are integrating MRI into their radiation
      therapy workflows. However, radiation therapy presents a new set of challenges
      and places additional constraints on MRI compared to diagnostic radiology that,
      if not properly addressed, can undermine the advantages MRI offers for radiation
      treatment planning (RTP). The authors introduce here strategies to manage several
      challenges of using MRI for virtual simulation in external beam RTP. METHODS: A
      total of 810 clinical MRI simulation exams were performed using a dedicated MRI
      scanner for external beam RTP of brain, breast, cervix, head and neck, liver,
      pancreas, prostate, and sarcoma cancers. Patients were imaged in treatment
      position using MRI-optimal immobilization devices. Radiofrequency (RF) coil
      configurations and scan protocols were optimized based on RTP constraints. Off
      resonance and gradient nonlinearity-induced geometric distortions were minimized
      or corrected prior to using images for RTP. A multidisciplinary MRI simulation
      guide, along with window width and level presets, was created to standardize use
      of MR images during RTP. A quality assurance program was implemented to maintain
      accuracy and repeatability of MRI simulation exams. RESULTS: The combination of a
      large bore scanner, high field strength, and circumferentially wrapped, flexible
      phased array RF receive coils permitted acquisition of thin slice images with
      high contrast-to-noise ratio (CNR) and image intensity uniformity, while
      simultaneously accommodating patient setup and immobilization devices.
      Postprocessing corrections and alternative acquisition methods were required to
      reduce or correct off-resonance and gradient nonlinearity induced geometric
      distortions. CONCLUSIONS: The methodology described herein contains practical
      strategies the authors have implemented through lessons learned performing
      clinical MRI simulation exams. In their experience, these strategies provide
      robust, high fidelity, high contrast MR images suitable for external beam RTP.

PMID- 25563244
TI  - Toward accurate tooth segmentation from computed tomography images using a hybrid
      level set model.
AB  - PURPOSE: A three-dimensional (3D) model of the teeth provides important
      information for orthodontic diagnosis and treatment planning. Tooth segmentation
      is an essential step in generating the 3D digital model from computed tomography
      (CT) images. The aim of this study is to develop an accurate and efficient tooth
      segmentation method from CT images. METHODS: The 3D dental CT volumetric images
      are segmented slice by slice in a two-dimensional (2D) transverse plane. The 2D
      segmentation is composed of a manual initialization step and an automatic slice
      by slice segmentation step. In the manual initialization step, the user manually
      picks a starting slice and selects a seed point for each tooth in this slice. In
      the automatic slice segmentation step, a developed hybrid level set model is
      applied to segment tooth contours from each slice. Tooth contour propagation
      strategy is employed to initialize the level set function automatically. Cone
      beam CT (CBCT) images of two subjects were used to tune the parameters. Images of
      16 additional subjects were used to validate the performance of the method.
      Volume overlap metrics and surface distance metrics were adopted to assess the
      segmentation accuracy quantitatively. The volume overlap metrics were volume
      difference (VD, mm(3)) and Dice similarity coefficient (DSC, %). The surface
      distance metrics were average symmetric surface distance (ASSD, mm), RMS (root
      mean square) symmetric surface distance (RMSSSD, mm), and maximum symmetric
      surface distance (MSSD, mm). Computation time was recorded to assess the
      efficiency. The performance of the proposed method has been compared with two
      state-of-the-art methods. RESULTS: For the tested CBCT images, the VD, DSC, ASSD,
      RMSSSD, and MSSD for the incisor were 38.16 +/- 12.94 mm(3), 88.82 +/- 2.14%,
      0.29 +/- 0.03 mm, 0.32 +/- 0.08 mm, and 1.25 +/- 0.58 mm, respectively; the VD,
      DSC, ASSD, RMSSSD, and MSSD for the canine were 49.12 +/- 9.33 mm(3), 91.57 +/-
      0.82%, 0.27 +/- 0.02 mm, 0.28 +/- 0.03 mm, and 1.06 +/- 0.40 mm, respectively;
      the VD, DSC, ASSD, RMSSSD, and MSSD for the premolar were 37.95 +/- 10.13 mm(3),
      92.45 +/- 2.29%, 0.29 +/- 0.06 mm, 0.33 +/- 0.10 mm, and 1.28 +/- 0.72 mm,
      respectively; the VD, DSC, ASSD, RMSSSD, and MSSD for the molar were 52.38 +/-
      17.27 mm(3), 94.12 +/- 1.38%, 0.30 +/- 0.08 mm, 0.35 +/- 0.17 mm, and 1.52 +/-
      0.75 mm, respectively. The computation time of the proposed method for segmenting
      CBCT images of one subject was 7.25 +/- 0.73 min. Compared with two other
      methods, the proposed method achieves significant improvement in terms of
      accuracy. CONCLUSIONS: The presented tooth segmentation method can be used to
      segment tooth contours from CT images accurately and efficiently.

PMID- 25563246
TI  - The ANACONDA algorithm for deformable image registration in radiotherapy.
AB  - PURPOSE: The purpose of this work was to describe a versatile algorithm for
      deformable image registration with applications in radiotherapy and to validate
      it on thoracic 4DCT data as well as CT/cone beam CT (CBCT) data. METHODS:
      ANAtomically CONstrained Deformation Algorithm (ANACONDA) combines image
      information (i.e., intensities) with anatomical information as provided by
      contoured image sets. The registration problem is formulated as a nonlinear
      optimization problem and solved with an in-house developed solver, tailored to
      this problem. The objective function, which is minimized during optimization, is
      a linear combination of four nonlinear terms: 1. image similarity term; 2. grid
      regularization term, which aims at keeping the deformed image grid smooth and
      invertible; 3. a shape based regularization term which works to keep the
      deformation anatomically reasonable when regions of interest are present in the
      reference image; and 4. a penalty term which is added to the optimization problem
      when controlling structures are used, aimed at deforming the selected structure
      in the reference image to the corresponding structure in the target image.
      RESULTS: To validate ANACONDA, the authors have used 16 publically available
      thoracic 4DCT data sets for which target registration errors from several
      algorithms have been reported in the literature. On average for the 16 data sets,
      the target registration error is 1.17 +/- 0.87 mm, Dice similarity coefficient is
      0.98 for the two lungs, and image similarity, measured by the correlation
      coefficient, is 0.95. The authors have also validated ANACONDA using two pelvic
      cases and one head and neck case with planning CT and daily acquired CBCT. Each
      image has been contoured by a physician (radiation oncologist) or experienced
      radiation therapist. The results are an improvement with respect to rigid
      registration. However, for the head and neck case, the sample set is too small to
      show statistical significance. CONCLUSIONS: ANACONDA performs well in comparison
      with other algorithms. By including CT/CBCT data in the validation, the various
      aspects of the algorithm such as its ability to handle different modalities,
      large deformations, and air pockets are shown.

PMID- 25563247
TI  - Efficient scatter distribution estimation and correction in CBCT using concurrent
      Monte Carlo fitting.
AB  - PURPOSE: X-ray scatter is a significant impediment to image quality improvements
      in cone-beam CT (CBCT). The authors present and demonstrate a novel scatter
      correction algorithm using a scatter estimation method that simultaneously
      combines multiple Monte Carlo (MC) CBCT simulations through the use of a
      concurrently evaluated fitting function, referred to as concurrent MC fitting
      (CMCF). METHODS: The CMCF method uses concurrently run MC CBCT scatter projection
      simulations that are a subset of the projection angles used in the projection
      set, P, to be corrected. The scattered photons reaching the detector in each MC
      simulation are simultaneously aggregated by an algorithm which computes the
      scatter detector response, SMC. SMC is fit to a function, SF, and if the fit of
      SF is within a specified goodness of fit (GOF), the simulations are terminated.
      The fit, SF, is then used to interpolate the scatter distribution over all pixel
      locations for every projection angle in the set P. The CMCF algorithm was tested
      using a frequency limited sum of sines and cosines as the fitting function on
      both simulated and measured data. The simulated data consisted of an
      anthropomorphic head and a pelvis phantom created from CT data, simulated with
      and without the use of a compensator. The measured data were a pelvis scan of a
      phantom and patient taken on an Elekta Synergy platform. The simulated data were
      used to evaluate various GOF metrics as well as determine a suitable fitness
      value. The simulated data were also used to quantitatively evaluate the image
      quality improvements provided by the CMCF method. A qualitative analysis was
      performed on the measured data by comparing the CMCF scatter corrected
      reconstruction to the original uncorrected and corrected by a constant scatter
      correction reconstruction, as well as a reconstruction created using a set of
      projections taken with a small cone angle. RESULTS: Pearson's correlation, r,
      proved to be a suitable GOF metric with strong correlation with the actual error
      of the scatter fit, SF. Fitting the scatter distribution to a limited sum of sine
      and cosine functions using a low-pass filtered fast Fourier transform provided a
      computationally efficient and accurate fit. The CMCF algorithm reduces the number
      of photon histories required by over four orders of magnitude. The simulated
      experiments showed that using a compensator reduced the computational time by a
      factor between 1.5 and 1.75. The scatter estimates for the simulated and measured
      data were computed between 35-93 s and 114-122 s, respectively, using 16 Intel
      Xeon cores (3.0 GHz). The CMCF scatter correction improved the contrast-to-noise
      ratio by 10%-50% and reduced the reconstruction error to under 3% for the
      simulated phantoms. CONCLUSIONS: The novel CMCF algorithm significantly reduces
      the computation time required to estimate the scatter distribution by reducing
      the statistical noise in the MC scatter estimate and limiting the number of
      projection angles that must be simulated. Using the scatter estimate provided by
      the CMCF algorithm to correct both simulated and real projection data showed
      improved reconstruction image quality.

PMID- 25563248
TI  - Comparing nonrigid registration techniques for motion corrected MR prostate
      diffusion imaging.
AB  - PURPOSE: T2-weighted magnetic resonance imaging (MRI) is commonly used for
      anatomical visualization in the pelvis area, such as the prostate, with high soft
      tissue contrast. MRI can also provide functional information such as diffusion
      weighted imaging (DWI) which depicts the molecular diffusion processes in
      biological tissues. The combination of anatomical and functional imaging
      techniques is widely used in oncology, e.g., for prostate cancer diagnosis and
      staging. However, acquisition-specific distortions as well as physiological
      motion lead to misalignments between T2 and DWI and consequently to a reduced
      diagnostic value. Image registration algorithms are commonly employed to correct
      for such misalignment. METHODS: The authors compare the performance of five state
      of-the-art nonrigid image registration techniques for accurate image fusion of
      DWI with T2. RESULTS: Image data of 20 prostate patients with cancerous lesions
      or cysts were acquired. All registration algorithms were validated using
      intensity-based as well as landmark-based techniques. CONCLUSIONS: The authors'
      results show that the "fast elastic image registration" provides most accurate
      results with a target registration error of 1.07 +/- 0.41 mm at minimum execution
      times of 11 +/- 1 s.

PMID- 25563250
TI  - A voxel-based multiscale model to simulate the radiation response of hypoxic
      tumors.
AB  - PURPOSE: In radiotherapy, it is important to predict the response of tumors to
      irradiation prior to the treatment. This is especially important for hypoxic
      tumors, which are known to be highly radioresistant. Mathematical modeling based
      on the dose distribution, biological parameters, and medical images may help to
      improve this prediction and to optimize the treatment plan. METHODS: A voxel
      based multiscale tumor response model for simulating the radiation response of
      hypoxic tumors was developed. It considers viable and dead tumor cells, capillary
      and normal cells, as well as the most relevant biological processes such as (i)
      proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial
      exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival
      after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of
      cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale
      using a previously published tumor oxygenation model, which calculates the oxygen
      distribution for each voxel using the vascular fraction as the most important
      input parameter. To demonstrate the capabilities of the model, the dependence of
      the oxygen distribution on tumor growth and radiation-induced shrinkage is
      investigated. In addition, the impact of three different reoxygenation processes
      is compared and tumor control probability (TCP) curves for a squamous cells
      carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic
      conditions. RESULTS: The model describes the spatiotemporal behavior of the tumor
      on three different scales: (i) on the macroscopic scale, it describes tumor
      growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it
      provides the cell density and vascular fraction for each voxel, and (iii) on the
      microscopic scale, the oxygen distribution may be obtained in terms of oxygen
      histograms. With increasing tumor size, the simulated tumors develop a hypoxic
      core. Within the model, tumor shrinkage was found to be significantly more
      important for reoxygenation than angiogenesis or decreased oxygen consumption due
      to an increased fraction of dead cells. In the studied HNSSC-case, the TCD50
      values (dose at 50% TCP) decreased from 71.0 Gy under hypoxic to 53.6 Gy under
      the oxic condition. CONCLUSIONS: The results obtained with the developed
      multiscale model are in accordance with expectations based on radiobiological
      principles and clinical experience. As the model is voxel-based, radiological
      imaging methods may help to provide the required 3D-characterization of the tumor
      prior to irradiation. For clinical application, the model has to be further
      validated with experimental and clinical data. If this is achieved, the model may
      be used to optimize fractionation schedules and dose distributions for the
      treatment of hypoxic tumors.

PMID- 25563249
TI  - Assessment of uncertainties in radiation-induced cancer risk predictions at
      clinically relevant doses.
AB  - PURPOSE: Theoretical dose-response models offer the possibility to assess second
      cancer induction risks after external beam therapy. The parameters used in these
      models are determined with limited data from epidemiological studies. Risk
      estimations are thus associated with considerable uncertainties. This study aims
      at illustrating uncertainties when predicting the risk for organ-specific second
      cancers in the primary radiation field illustrated by choosing selected treatment
      plans for brain cancer patients. METHODS: A widely used risk model was considered
      in this study. The uncertainties of the model parameters were estimated with
      reported data of second cancer incidences for various organs. Standard error
      propagation was then subsequently applied to assess the uncertainty in the risk
      model. Next, second cancer risks of five pediatric patients treated for cancer in
      the head and neck regions were calculated. For each case, treatment plans for
      proton and photon therapy were designed to estimate the uncertainties (a) in the
      lifetime attributable risk (LAR) for a given treatment modality and (b) when
      comparing risks of two different treatment modalities. RESULTS: Uncertainties in
      excess of 100% of the risk were found for almost all organs considered. When
      applied to treatment plans, the calculated LAR values have uncertainties of the
      same magnitude. A comparison between cancer risks of different treatment
      modalities, however, does allow statistically significant conclusions. In the
      studied cases, the patient averaged LAR ratio of proton and photon treatments was
      0.35, 0.56, and 0.59 for brain carcinoma, brain sarcoma, and bone sarcoma,
      respectively. Their corresponding uncertainties were estimated to be potentially
      below 5%, depending on uncertainties in dosimetry. CONCLUSIONS: The uncertainty
      in the dose-response curve in cancer risk models makes it currently impractical
      to predict the risk for an individual external beam treatment. On the other hand,
      the ratio of absolute risks between two modalities is less sensitive to the
      uncertainties in the risk model and can provide statistically significant
      estimates.

PMID- 25563251
TI  - A new quantitative image analysis method for improving breast cancer diagnosis
      using DCE-MRI examinations.
AB  - PURPOSE: To investigate the feasibility of applying a new quantitative image
      analysis method to improve breast cancer diagnosis performance using dynamic
      contrast enhanced magnetic resonance imaging (DCE-MRI) by integrating background
      parenchymal enhancement (BPE) features into the decision making process. METHODS:
      A dataset involving 115 DCE-MRI examinations was used in this study. Each
      examination depicts one identified suspicious breast tumor. Among them, 75 cases
      were verified as malignant and 40 were benign by the biopsy results. A computer
      aided detection scheme was applied to segment breast regions and the suspicious
      tumor depicted on the sequentially scanned MR images of each case. We then
      computed 18 kinetic features in which 6 were computed from the segmented breast
      tumor and 12 were BPE features from the background parenchymal regions (excluding
      the tumor). Support vector machine (SVM) based statistical learning classifiers
      were trained and optimized using different combinations of features that were
      computed either from tumor only or from both tumor and BPE. Each SVM was tested
      using a leave-one-case-out validation method and assessed using an area under the
      receiver operating characteristic curve (AUC). RESULTS: When using kinetic
      features computed from tumors only, the maximum AUC is 0.865 +/- 0.035. After
      fusing with the BPE features, AUC increased to 0.919 +/- 0.029. At 90%
      specificity, the tumor classification sensitivity increased by 13.2%.
      CONCLUSIONS: The proposed quantitative BPE features provide valuable
      supplementary information to the kinetic features of breast tumors in DCE-MRI.
      Their addition to computer-aided diagnosis methodologies could improve breast
      cancer diagnosis based on DCE-MRI examinations.

PMID- 25563253
TI  - Using compressive sensing to recover images from PET scanners with partial
      detector rings.
AB  - PURPOSE: Most positron emission tomography/computed tomography (PET/CT) scanners
      consist of tightly packed discrete detector rings to improve scanner efficiency.
      The authors' aim was to use compressive sensing (CS) techniques in PET imaging to
      investigate the possibility of decreasing the number of detector elements per
      ring (introducing gaps) while maintaining image quality. METHODS: A CS model
      based on a combination of gradient magnitude and wavelet domains (wavelet-TV) was
      developed to recover missing observations in PET data acquisition. The model was
      designed to minimize the total variation (TV) and L1-norm of wavelet coefficients
      while constrained by the partially observed data. The CS model also incorporated
      a Poisson noise term that modeled the observed noise while suppressing its
      contribution by penalizing the Poisson log likelihood function. Three experiments
      were performed to evaluate the proposed CS recovery algorithm: a simulation
      study, a phantom study, and six patient studies. The simulation dataset comprised
      six disks of various sizes in a uniform background with an activity concentration
      of 5:1. The simulated image was multiplied by the system matrix to obtain the
      corresponding sinogram and then Poisson noise was added. The resultant sinogram
      was masked to create the effect of partial detector removal and then the proposed
      CS algorithm was applied to recover the missing PET data. In addition, different
      levels of noise were simulated to assess the performance of the proposed
      algorithm. For the phantom study, an IEC phantom with six internal spheres each
      filled with F-18 at an activity-to-background ratio of 10:1 was used. The phantom
      was imaged twice on a RX PET/CT scanner: once with all detectors operational
      (baseline) and once with four detector blocks (11%) turned off at each of 0 , 90
      , 180 , and 270 degrees  (partially sampled). The partially acquired sinograms
      were then recovered using the proposed algorithm. For the third test, PET images
      from six patient studies were investigated using the same strategy of the phantom
      study. The recovered images using WTV and TV as well as the partially sampled
      images from all three experiments were then compared with the fully sampled
      images (the baseline). Comparisons were done by calculating the mean error
      (%bias), root mean square error (RMSE), contrast recovery (CR), and SNR of
      activity concentration in regions of interest drawn in the background as well as
      the disks, spheres, and lesions. RESULTS: For the simulation study, the mean
      error, RMSE, and CR for the WTV (TV) recovered images were 0.26% (0.48%), 2.6%
      (2.9%), 97% (96%), respectively, when compared to baseline. For the partially
      sampled images, these results were 22.5%, 45.9%, and 64%, respectively. For the
      simulation study, the average SNR for the baseline was 41.7 while for WTV (TV),
      recovered image was 44.2 (44.0). The phantom study showed similar trends with
      5.4% (18.2%), 15.6% (18.8%), and 78% (60%), respectively, for the WTV (TV) images
      and 33%, 34.3%, and 69% for the partially sampled images. For the phantom study,
      the average SNR for the baseline was 14.7 while for WTV (TV) recovered image was
      13.7 (11.9). Finally, the average of these values for the six patient studies for
      the WTV-recovered, TV, and partially sampled images was 1%, 7.2%, 92% and 1.3%,
      15.1%, 87%, and 27%, 25.8%, 45%, respectively. CONCLUSIONS: CS with WTV is
      capable of recovering PET images with good quantitative accuracy from partially
      sampled data. Such an approach can be used to potentially reduce the cost of
      scanners while maintaining good image quality.

PMID- 25563252
TI  - Impact of CT attenuation correction method on quantitative respiratory-correlated
      (4D) PET/CT imaging.
AB  - PURPOSE: Respiratory-correlated positron emission tomography (PET/CT) 4D PET/CT
      is used to mitigate errors from respiratory motion; however, the optimal CT
      attenuation correction (CTAC) method for 4D PET/CT is unknown. The authors
      performed a phantom study to evaluate the quantitative performance of CTAC
      methods for 4D PET/CT in the ground truth setting. METHODS: A programmable
      respiratory motion phantom with a custom movable insert designed to emulate a
      lung lesion and lung tissue was used for this study. The insert was driven by one
      of five waveforms: two sinusoidal waveforms or three patient-specific respiratory
      waveforms. 3DPET and 4DPET images of the phantom under motion were acquired and
      reconstructed with six CTAC methods: helical breath-hold (3DHEL), helical free
      breathing (3DMOT), 4D phase-averaged (4DAVG), 4D maximum intensity projection
      (4DMIP), 4D phase-matched (4DMATCH), and 4D end-exhale (4DEXH) CTAC. Recovery of
      SUV(max), SUV(mean), SUV(peak), and segmented tumor volume was evaluated as
      RC(max), RC(mean), RC(peak), and RC(vol), representing percent difference
      relative to the static ground truth case. Paired Wilcoxon tests and Kruskal
      Wallis ANOVA were used to test for significant differences. RESULTS: For 4DPET
      imaging, the maximum intensity projection CTAC produced significantly more
      accurate recovery coefficients than all other CTAC methods (p < 0.0001 over all
      metrics). Over all motion waveforms, ratios of 4DMIP CTAC recovery were 0.2 +/-
      5.4, -1.8 +/- 6.5, -3.2 +/- 5.0, and 3.0 +/- 5.9 for RC(max), RC(peak), RC(mean),
      and RC(vol). In comparison, recovery coefficients for phase-matched CTAC were 
      8.4 +/- 5.3, -10.5 +/- 6.2, -7.6 +/- 5.0, and -13.0 +/- 7.7 for RC(max),
      RC(peak), RC(mean), and RC(vol). When testing differences between phases over all
      CTAC methods and waveforms, end-exhale phases were significantly more accurate (p
      = 0.005). However, these differences were driven by the patient-specific
      respiratory waveforms; when testing patient and sinusoidal waveforms separately,
      patient waveforms were significantly different between phases (p < 0.0001) while
      the sinusoidal waveforms were not significantly different (p = 0.98). When
      considering only the subset of 4DMATCH images that corresponded to the end-exhale
      image phase, 4DEXH, mean and interquartile range were similar to 4DMATCH but
      variability was considerably reduced. CONCLUSIONS: Comparative advantages in
      accuracy and precision of SUV metrics and segmented volumes were demonstrated
      with the use of the maximum intensity projection and end-exhale CT attenuation
      correction. While respiratory phase-matched CTAC should in theory provide optimal
      corrections, image artifacts and differences in implementation of 4DCT and 4DPET
      sorting can degrade the benefit of this approach. These results may be useful to
      guide the implementation, analysis, and development of respiratory-correlated
      thoracic PET/CT in the radiation oncology and diagnostic settings.

PMID- 25563254
TI  - Monitoring ABC-assisted deep inspiration breath hold for left-sided breast
      radiotherapy with an optical tracking system.
AB  - PURPOSE: Recent knowledge on the effects of cardiac toxicity warrants greater
      precision for left-sided breast radiotherapy. Different breath-hold (BH)
      maneuvers (abdominal vs thoracic breathing) can lead to chest wall positional
      variations, even though the patient's tidal volume remains consistent. This study
      aims to investigate the feasibility of using optical tracking for real-time
      quality control of active breathing coordinator (ABC)-assisted deep inspiration
      BH (DIBH). METHODS: An in-house optical tracking system (OTS) was used to monitor
      ABC-assisted DIBH. The stability and localization accuracy of the OTS were
      assessed with a ball-bearing phantom. Seven patients with left-sided breast
      cancer were included. A free-breathing (FB) computed tomography (CT) scan and an
      ABC-assisted BH CT scan were acquired for each patient. The OTS tracked an
      infrared (IR) marker affixed over the patient's xiphoid process to measure the
      positional variation of each individual BH. Using the BH within which the CT scan
      was performed as the reference, the authors quantified intra- and interfraction
      BH variations for each patient. To estimate the dosimetric impact of BH
      variations, the authors studied the positional correlation between the marker and
      the left breast using the FB CT and BH CT scans. The positional variations of 860
      BHs as measured by the OTS were retrospectively incorporated into the original
      treatment plans to evaluate their dosimetric impact on breast and cardiac organs
      [heart and left anterior descending (LAD) artery]. RESULTS: The stability and
      localization accuracy of the OTS was within 0.2 mm along each direction. The mean
      intrafraction variation among treatment BHs was less than 2.8 mm in all
      directions. Up to 12.6 mm anteroposterior undershoot, where the patient's chest
      wall displacement of a BH is less than that of a reference BH, was observed with
      averages of 4.4, 3.6, and 0.1 mm in the anteroposterior, craniocaudal, and
      mediolateral directions, respectively. A high positional correlation between the
      marker and the breast was found in the anteroposterior and craniocaudal
      directions with respective Pearson correlation values of 0.95 and 0.93, but no
      mediolateral correlation was found. Dosimetric impact of BH variations on breast
      coverage was negligible. However, the mean heart dose, mean LAD dose, and max LAD
      dose were estimated to increase from 1.4/7.4/18.6 Gy (planned) to 2.1/15.7/31.0
      Gy (delivered), respectively. CONCLUSIONS: In ABC-assisted DIBH, large positional
      variation can occur in some patients, due to their different BH maneuvers. The
      authors' study has shown that OTS can be a valuable tool for real-time quality
      control of ABC-assisted DIBH.

PMID- 25563255
TI  - Computer-aided detection of renal calculi from noncontrast CT images using TV
      flow and MSER features.
AB  - PURPOSE: Renal calculi are common extracolonic incidental findings on computed
      tomographic colonography (CTC). This work aims to develop a fully automated
      computer-aided diagnosis system to accurately detect renal calculi on CTC images.
      METHODS: The authors developed a total variation (TV) flow method to reduce image
      noise within the kidneys while maintaining the characteristic appearance of renal
      calculi. Maximally stable extremal region (MSER) features were then calculated to
      robustly identify calculi candidates. Finally, the authors computed texture and
      shape features that were imported to support vector machines for calculus
      classification. The method was validated on a dataset of 192 patients and
      compared to a baseline approach that detects calculi by thresholding. The authors
      also compared their method with the detection approaches using anisotropic
      diffusion and nonsmoothing. RESULTS: At a false positive rate of 8 per patient,
      the sensitivities of the new method and the baseline thresholding approach were
      69% and 35% (p < 1e - 3) on all calculi from 1 to 433 mm(3) in the testing
      dataset. The sensitivities of the detection methods using anisotropic diffusion
      and nonsmoothing were 36% and 0%, respectively. The sensitivity of the new method
      increased to 90% if only larger and more clinically relevant calculi were
      considered. CONCLUSIONS: Experimental results demonstrated that TV-flow and MSER
      features are efficient means to robustly and accurately detect renal calculi on
      low-dose, high noise CTC images. Thus, the proposed method can potentially
      improve diagnosis.

PMID- 25563257
TI  - GPU-based prompt gamma ray imaging from boron neutron capture therapy.
AB  - PURPOSE: The purpose of this research is to perform the fast reconstruction of a
      prompt gamma ray image using a graphics processing unit (GPU) computation from
      boron neutron capture therapy (BNCT) simulations. METHODS: To evaluate the
      accuracy of the reconstructed image, a phantom including four boron uptake
      regions (BURs) was used in the simulation. After the Monte Carlo simulation of
      the BNCT, the modified ordered subset expectation maximization reconstruction
      algorithm using the GPU computation was used to reconstruct the images with fewer
      projections. The computation times for image reconstruction were compared between
      the GPU and the central processing unit (CPU). Also, the accuracy of the
      reconstructed image was evaluated by a receiver operating characteristic (ROC)
      curve analysis. RESULTS: The image reconstruction time using the GPU was 196
      times faster than the conventional reconstruction time using the CPU. For the
      four BURs, the area under curve values from the ROC curve were 0.6726 (A-region),
      0.6890 (B-region), 0.7384 (C-region), and 0.8009 (D-region). CONCLUSIONS: The
      tomographic image using the prompt gamma ray event from the BNCT simulation was
      acquired using the GPU computation in order to perform a fast reconstruction
      during treatment. The authors verified the feasibility of the prompt gamma ray
      image reconstruction using the GPU computation for BNCT simulations.

PMID- 25563256
TI  - Evaluation of intrinsic respiratory signal determination methods for 4D CBCT
      adapted for mice.
AB  - PURPOSE: 4D CT imaging in mice is important in a variety of areas including
      studies of lung function and tumor motion. A necessary step in 4D imaging is
      obtaining a respiratory signal, which can be done through an external system or
      intrinsically through the projection images. A number of methods have been
      developed that can successfully determine the respiratory signal from cone-beam
      projection images of humans, however only a few have been utilized in a
      preclinical setting and most of these rely on step-and-shoot style imaging. The
      purpose of this work is to assess and make adaptions of several successful
      methods developed for humans for an image-guided preclinical radiation therapy
      system. METHODS: Respiratory signals were determined from the projection images
      of free-breathing mice scanned on the X-RAD system using four methods: the so
      called Amsterdam shroud method, a method based on the phase of the Fourier
      transform, a pixel intensity method, and a center of mass method. The Amsterdam
      shroud method was modified so the sharp inspiration peaks associated with
      anesthetized mouse breathing could be detected. Respiratory signals were used to
      sort projections into phase bins and 4D images were reconstructed. Error and
      standard deviation in the assignment of phase bins for the four methods compared
      to a manual method considered to be ground truth were calculated for a range of
      region of interest (ROI) sizes. Qualitative comparisons were additionally made
      between the 4D images obtained using each of the methods and the manual method.
      RESULTS: 4D images were successfully created for all mice with each of the
      respiratory signal extraction methods. Only minimal qualitative differences were
      noted between each of the methods and the manual method. The average error (and
      standard deviation) in phase bin assignment was 0.24 +/- 0.08 (0.49 +/- 0.11)
      phase bins for the Fourier transform method, 0.09 +/- 0.03 (0.31 +/- 0.08) phase
      bins for the modified Amsterdam shroud method, 0.09 +/- 0.02 (0.33 +/- 0.07)
      phase bins for the intensity method, and 0.37 +/- 0.10 (0.57 +/- 0.08) phase bins
      for the center of mass method. Little dependence on ROI size was noted for the
      modified Amsterdam shroud and intensity methods while the Fourier transform and
      center of mass methods showed a noticeable dependence on the ROI size.
      CONCLUSIONS: The modified Amsterdam shroud, Fourier transform, and intensity
      respiratory signal methods are sufficiently accurate to be used for 4D imaging on
      the X-RAD system and show improvement over the existing center of mass method.
      The intensity and modified Amsterdam shroud methods are recommended due to their
      high accuracy and low dependence on ROI size.

PMID- 25563258
TI  - Exogenous contrast agents for thermoacoustic imaging: an investigation into the
      underlying sources of contrast.
AB  - PURPOSE: Thermoacoustic imaging at microwave excitation frequencies is limited by
      the low differential contrast exhibited by high water content tissues. To
      overcome this, exogenous thermoacoustic contrast agents based on gadolinium
      compounds, iron oxide, and single wall carbon nanotubes have previously been
      suggested and investigated. However, these previous studies did not fully
      characterize the electric, magnetic, and thermodynamic properties of these agents
      thus precluding identification of the underlying sources of contrast. To address
      this, measurements of the complex permittivity, complex permeability, DC
      conductivity, and Gruneisen parameter have been made. These measurements allowed
      the origins of the contrast provided by each substance to be identified. METHODS:
      The electric and magnetic properties of the contrast agents were characterized at
      3 GHz using two rectangular waveguide cavities. The DC conductivity was measured
      separately using a conductivity meter. Thermoacoustic signals were then acquired
      and compared to those generated in water. Finally, 3D electromagnetic simulations
      were used to decouple the different contributions to the absorbed power density.
      RESULTS: It was found that the gadolinium compounds provided appreciable electric
      contrast but not originating from the gadolinium itself. The contrast was either
      due to dissociation of the gadolinium salt which increased ionic conductivity or
      its nondissociated polar fraction which increased dielectric polarization loss or
      a combination of both. In addition, very high concentrations were required to
      achieve appreciable contrast, to the extent that the Gruneisen parameter
      increased significantly and became a source of contrast. Iron oxide particles
      were found to produce low but measurable dielectric contrast due to dielectric
      polarization loss, but this is attributed to the coating of the particles not the
      iron oxide. Single wall carbon nanotubes did not provide measurable contrast of
      any type. CONCLUSIONS: It is concluded that gadolinium based contrast agents,
      iron oxide particles, and single walled carbon nanotubes have little intrinsic
      merit as thermoacoustic contrast agents. Simple electrolytes such as saline which
      yield high contrast based on ionic conductivity provide much higher dielectric
      contrast per unit solute concentration and are likely to be significantly more
      effective as contrast agents.

PMID- 25563259
TI  - Multiscale bilateral filtering for improving image quality in digital breast
      tomosynthesis.
AB  - PURPOSE: Detection of subtle microcalcifications in digital breast tomosynthesis
      (DBT) is a challenging task because of the large, noisy DBT volume. It is
      important to enhance the contrast-to-noise ratio (CNR) of microcalcifications in
      DBT reconstruction. Most regularization methods depend on local gradient and may
      treat the ill-defined margins or subtle spiculations of masses and subtle
      microcalcifications as noise because of their small gradient. The authors
      developed a new multiscale bilateral filtering (MSBF) regularization method for
      the simultaneous algebraic reconstruction technique (SART) to improve the CNR of
      microcalcifications without compromising the quality of masses. METHODS: The MSBF
      exploits a multiscale structure of DBT images to suppress noise and selectively
      enhance high frequency structures. At the end of each SART iteration, every DBT
      slice is decomposed into several frequency bands via Laplacian pyramid
      decomposition. No regularization is applied to the low frequency bands so that
      subtle edges of masses and structured background are preserved. Bilateral
      filtering is applied to the high frequency bands to enhance microcalcifications
      while suppressing noise. The regularized DBT images are used for updating in the
      next SART iteration. The new MSBF method was compared with the nonconvex total p
      variation (TpV) method for noise regularization with SART. A GE GEN2 prototype
      DBT system was used for acquisition of projections at 21 angles in 3 degrees 
      increments over a +/- 30 degrees  range. The reconstruction image quality with no
      regularization (NR) and that with the two regularization methods were compared
      using the DBT scans of a heterogeneous breast phantom and several human subjects
      with masses and microcalcifications. The CNR and the full width at half maximum
      (FWHM) of the line profiles of microcalcifications and across the spiculations
      within their in-focus DBT slices were used as image quality measures. RESULTS:
      The MSBF method reduced contouring artifacts and enhanced the CNR of
      microcalcifications compared to the TpV method, thus preserving the image quality
      of the structured background. The MSBF method achieved the highest CNR of
      microcalcifications among the three methods. The FWHM of the microcalcifications
      and mass spiculations resulting from the MSBF method was comparable to that
      without regularization, and superior to that of the TpV method. CONCLUSIONS: The
      SART regularized by the multiscale bilateral filtering method enhanced the CNR of
      microcalcifications and preserved the sharpness of microcalcifications and
      spiculated masses. The MSBF method provided better image quality of the
      structured background and was superior to TpV and NR for enhancing
      microcalcifications while preserving the appearance of mass margins.

PMID- 25563260
TI  - Validation of a deformable image registration technique for cone beam CT-based
      dose verification.
AB  - PURPOSE: As radiation therapy evolves toward more adaptive techniques, image
      guidance plays an increasingly important role, not only in patient setup but also
      in monitoring the delivered dose and adapting the treatment to patient changes.
      This study aimed to validate a method for evaluation of delivered intensity
      modulated radiotherapy (IMRT) dose based on multimodal deformable image
      registration (dir) for prostate treatments. METHODS: A pelvic phantom was scanned
      with CT and cone-beam computed tomography (CBCT). Both images were digitally
      deformed using two realistic patient-based deformation fields. The original CT
      was then registered to the deformed CBCT resulting in a secondary deformed CT.
      The registration quality was assessed as the ability of the dir method to recover
      the artificially induced deformations. The primary and secondary deformed CT
      images as well as vector fields were compared to evaluate the efficacy of the
      registration method and it's suitability to be used for dose calculation.
      plastimatch, a free and open source software was used for deformable image
      registration. A B-spline algorithm with optimized parameters was used to achieve
      the best registration quality. Geometric image evaluation was performed through
      voxel-based Hounsfield unit (HU) and vector field comparison. For dosimetric
      evaluation, IMRT treatment plans were created and optimized on the original CT
      image and recomputed on the two warped images to be compared. The dose volume
      histograms were compared for the warped structures that were identical in both
      warped images. This procedure was repeated for the phantom with full, half full,
      and empty bladder. RESULTS: The results indicated mean HU differences of up to
      120 between registered and ground-truth deformed CT images. However, when the
      CBCT intensities were calibrated using a region of interest (ROI)-based
      calibration curve, these differences were reduced by up to 60%. Similarly, the
      mean differences in average vector field lengths decreased from 10.1 to 2.5 mm
      when CBCT was calibrated prior to registration. The results showed no dependence
      on the level of bladder filling. In comparison with the dose calculated on the
      primary deformed CT, differences in mean dose averaged over all organs were 0.2%
      and 3.9% for dose calculated on the secondary deformed CT with and without CBCT
      calibration, respectively, and 0.5% for dose calculated directly on the
      calibrated CBCT, for the full-bladder scenario. Gamma analysis for the distance
      to agreement of 2 mm and 2% of prescribed dose indicated a pass rate of 100% for
      both cases involving calibrated CBCT and on average 86% without CBCT calibration.
      CONCLUSIONS: Using deformable registration on the planning CT images to evaluate
      the IMRT dose based on daily CBCTs was found feasible. The proposed method will
      provide an accurate dose distribution using planning CT and pretreatment CBCT
      data, avoiding the additional uncertainties introduced by CBCT inhomogeneity and
      artifacts. This is a necessary initial step toward future image-guided adaptive
      radiotherapy of the prostate.

PMID- 25563262
TI  - A universal dose-response curve for radiochromic films.
AB  - PURPOSE: This paper presents a model for dose-response curves of radiochromic
      films. It is based on a modified version of single-hit model to take into account
      the growth experienced by lithium salt of pentacosa-10,12-diynoic acid polymers
      after irradiation. METHODS: Polymer growth in radiochromic films is a critical
      phenomenon that can be properly described by means of percolation theory to
      provide an appropriate distribution function for polymer sizes. Resulting
      functional form is a power function featuring a critical exponent and two
      adjustable parameters. Moreover, these parameters act as scaling factors setting
      a natural scale for sensitometric curves where the dependence on channel
      sensitivity is removed. A unique reduced response curve is then obtained from all
      the color channels describing film behavior independently of film dosimetry
      system. RESULTS: Resulting functional form has been successfully tested in
      several sensitometric curves from different Gafchromic EBT models, providing
      excellent agreement with experimental data in a wide dose range up to about 40 Gy
      and low dose uncertainty. CONCLUSIONS: The model presented in this paper
      describes accurately the sensitometric curves of radiochromic films in wide dose
      ranges covering all typical ranges used in external radiotherapy. Resulting dose
      uncertainty is low enough to render a reasonably good performance in clinical
      applications. Due to cross-correlation, only one of the adjustable parameters is
      totally independent and characterizes film batches.

PMID- 25563261
TI  - Improving anatomical mapping of complexly deformed anatomy for external beam
      radiotherapy and brachytherapy dose accumulation in cervical cancer.
AB  - PURPOSE: In the treatment of cervical cancer, large anatomical deformations,
      caused by, e.g., tumor shrinkage, bladder and rectum filling changes, organ
      sliding, and the presence of the brachytherapy (BT) applicator, prohibit the
      accumulation of external beam radiotherapy (EBRT) and BT dose distributions. This
      work proposes a structure-wise registration with vector field integration (SW+VF)
      to map the largely deformed anatomies between EBRT and BT, paving the way for 3D
      dose accumulation between EBRT and BT. METHODS: T2w-MRIs acquired before EBRT and
      as a part of the MRI-guided BT procedure for 12 cervical cancer patients, along
      with the manual delineations of the bladder, cervix-uterus, and rectum-sigmoid,
      were used for this study. A rigid transformation was used to align the bony
      anatomy in the MRIs. The proposed SW+VF method starts by automatically segmenting
      features in the area surrounding the delineated organs. Then, each organ and
      feature pair is registered independently using a feature-based nonrigid
      registration algorithm developed in-house. Additionally, a background
      transformation is calculated to account for areas far from all organs and
      features. In order to obtain one transformation that can be used for dose
      accumulation, the organ-based, feature-based, and the background transformations
      are combined into one vector field using a weighted sum, where the contribution
      of each transformation can be directly controlled by its extent of influence
      (scope size). The optimal scope sizes for organ-based and feature-based
      transformations were found by an exhaustive analysis. The anatomical correctness
      of the mapping was independently validated by measuring the residual distances
      after transformation for delineated structures inside the cervix-uterus (inner
      anatomical correctness), and for anatomical landmarks outside the organs in the
      surrounding region (outer anatomical correctness). The results of the proposed
      method were compared with the results of the rigid transformation and nonrigid
      registration of all structures together (AST). RESULTS: The rigid transformation
      achieved a good global alignment (mean outer anatomical correctness of 4.3 mm)
      but failed to align the deformed organs (mean inner anatomical correctness of
      22.4 mm). Conversely, the AST registration produced a reasonable alignment for
      the organs (6.3 mm) but not for the surrounding region (16.9 mm). SW+VF
      registration achieved the best results for both regions (3.5 and 3.4 mm for the
      inner and outer anatomical correctness, respectively). All differences were
      significant (p < 0.02, Wilcoxon rank sum test). Additionally, optimization of the
      scope sizes determined that the method was robust for a large range of scope size
      values. CONCLUSIONS: The novel SW+VF method improved the mapping of large and
      complex deformations observed between EBRT and BT for cervical cancer patients.
      Future studies that quantify the mapping error in terms of dose errors are
      required to test the clinical applicability of dose accumulation by the SW+VF
      method.

PMID- 25563263
TI  - A GPU based high-resolution multilevel biomechanical head and neck model for
      validating deformable image registration.
AB  - PURPOSE: Validating the usage of deformable image registration (dir) for daily
      patient positioning is critical for adaptive radiotherapy (RT) applications
      pertaining to head and neck (HN) radiotherapy. The authors present a methodology
      for generating biomechanically realistic ground-truth data for validating dir
      algorithms for HN anatomy by (a) developing a high-resolution deformable
      biomechanical HN model from a planning CT, (b) simulating deformations for a
      range of interfraction posture changes and physiological regression, and (c)
      generating subsequent CT images representing the deformed anatomy. METHODS: The
      biomechanical model was developed using HN kVCT datasets and the corresponding
      structure contours. The voxels inside a given 3D contour boundary were clustered
      using a graphics processing unit (GPU) based algorithm that accounted for
      inconsistencies and gaps in the boundary to form a volumetric structure. While
      the bony anatomy was modeled as rigid body, the muscle and soft tissue structures
      were modeled as mass-spring-damper models with elastic material properties that
      corresponded to the underlying contoured anatomies. Within a given muscle
      structure, the voxels were classified using a uniform grid and a normalized mass
      was assigned to each voxel based on its Hounsfield number. The soft tissue
      deformation for a given skeletal actuation was performed using an implicit Euler
      integration with each iteration split into two substeps: one for the muscle
      structures and the other for the remaining soft tissues. Posture changes were
      simulated by articulating the skeletal structure and enabling the soft structures
      to deform accordingly. Physiological changes representing tumor regression were
      simulated by reducing the target volume and enabling the surrounding soft
      structures to deform accordingly. Finally, the authors also discuss a new
      approach to generate kVCT images representing the deformed anatomy that accounts
      for gaps and antialiasing artifacts that may be caused by the biomechanical
      deformation process. Accuracy and stability of the model response were validated
      using ground-truth simulations representing soft tissue behavior under local and
      global deformations. Numerical accuracy of the HN deformations was analyzed by
      applying nonrigid skeletal transformations acquired from interfraction kVCT
      images to the model's skeletal structures and comparing the subsequent soft
      tissue deformations of the model with the clinical anatomy. RESULTS: The GPU
      based framework enabled the model deformation to be performed at 60 frames/s,
      facilitating simulations of posture changes and physiological regressions at
      interactive speeds. The soft tissue response was accurate with a R(2) value of
      >0.98 when compared to ground-truth global and local force deformation analysis.
      The deformation of the HN anatomy by the model agreed with the clinically
      observed deformations with an average correlation coefficient of 0.956. For a
      clinically relevant range of posture and physiological changes, the model
      deformations stabilized with an uncertainty of less than 0.01 mm. CONCLUSIONS:
      Documenting dose delivery for HN radiotherapy is essential accounting for posture
      and physiological changes. The biomechanical model discussed in this paper was
      able to deform in real-time, allowing interactive simulations and visualization
      of such changes. The model would allow patient specific validations of the dir
      method and has the potential to be a significant aid in adaptive radiotherapy
      techniques.

PMID- 25563264
TI  - A method of surface marker location optimization for tumor motion estimation in
      lung stereotactic body radiation therapy.
AB  - PURPOSE: Accurately localizing lung tumor localization is essential for high
      precision radiation therapy techniques such as stereotactic body radiation
      therapy (SBRT). Since direct monitoring of tumor motion is not always achievable
      due to the limitation of imaging modalities for treatment guidance, placement of
      fiducial markers on the patient's body surface to act as a surrogate for tumor
      position prediction is a practical alternative for tracking lung tumor motion
      during SBRT treatments. In this work, the authors propose an innovative and
      robust model to solve the multimarker position optimization problem. The model is
      able to overcome the major drawbacks of the sparse optimization approach (SOA)
      model. METHODS: The principle-component-analysis (PCA) method was employed as the
      framework to build the authors' statistical prediction model. The method can be
      divided into two stages. The first stage is to build the surrogate tumor matrix
      and calculate its eigenvalues and associated eigenvectors. The second stage is to
      determine the "best represented" columns of the eigenvector matrix obtained from
      stage one and subsequently acquire the optimal marker positions as well as
      numbers. Using 4-dimensional CT (4 DCT) and breath hold CT imaging data, the PCA
      method was compared to the SOA method with respect to calculation time, average
      prediction accuracy, prediction stability, noise resistance, marker position
      consistency, and marker distribution. RESULTS: The PCA and SOA methods which were
      both tested were on all 11 patients for a total of 130 cases including 4 DCT and
      breath-hold CT scenarios. The maximum calculation time for the PCA method was
      less than 1 s with 64 752 surface points, whereas the average calculation time
      for the SOA method was over 12 min with 400 surface points. Overall, the tumor
      center position prediction errors were comparable between the two methods, and
      all were less than 1.5 mm. However, for the extreme scenarios (breath hold), the
      prediction errors for the PCA method were not only smaller, but were also more
      stable than for the SOA method. Results obtained by imposing a series of random
      noises to the surrogates indicated that the PCA method was much more noise
      resistant than the SOA method. The marker position consistency tests using
      various combinations of 4 DCT phases to construct the surrogates suggested that
      the marker position predictions of the PCA method were more consistent than those
      of the SOA method, in spite of surrogate construction. Marker distribution tests
      indicated that greater than 80% of the calculated marker positions fell into the
      high cross correlation and high motion magnitude regions for both of the
      algorithms. CONCLUSIONS: The PCA model is an accurate, efficient, robust, and
      practical model for solving the multimarker position optimization problem to
      predict lung tumor motion during SBRT treatments. Due to its generality, PCA
      model can also be applied to other imaging guidance system whichever using
      surface motion as the surrogates.

PMID- 25563265
TI  - Markerless motion tracking of lung tumors using dual-energy fluoroscopy.
AB  - PURPOSE: To evaluate the efficacy of dual-energy (DE) vs single-energy (SE)
      fluoroscopic imaging of lung tumors using a markerless template-based tracking
      algorithm. METHODS: Ten representative patient breathing patterns were programmed
      into a QuasarTM motion phantom. The phantom was modified by affixing pork ribs to
      the surface, and a cedar insert with a small spherical volume was used to
      simulate lung and tumor, respectively. Sequential 60 kVp (6 mA) and 120 kVp (1.5
      mA) fluoroscopic sequences were acquired. Frame-by-frame weighted logarithmic
      subtraction was performed resulting in a DE fluoroscopic sequence. A template
      based algorithm was then used to track tumor motion throughout the DE and SE
      fluoroscopy sequences. Tracking coordinates were evaluated against ground-truth
      tumor locations. Fluoroscopic images were also acquired for two lung cancer
      patients, neither of which had implanted fiducials. RESULTS: For phantom imaging,
      a total of 1925 frames were analyzed. The algorithm successfully tracked the
      target on 99.9% (1923/1925) of DE frames vs 90.7% (1745/1925) SE images (p <
      0.01). The displacement between tracking coordinates and ground truth for the
      phantom was 1.4 mm +/- 1.1 mm for DE vs 2.0 mm +/- 1.3 mm for SE (p < 0.01).
      Images from two patients, one with a larger tumor and one with a smaller tumor,
      were also analyzed. For the patient with the larger tumor, the average
      displacement from physician defined ground truth was 1.2 mm +/- 0.6 mm for DE vs
      1.4 mm +/- 0.7 mm for SE (p = 0.016). For the patient that presented with a
      smaller tumor, the average displacement from physician defined ground truth was
      2.2 mm +/- 1.0 mm for DE vs 3.2 mm +/- 1.4 mm for SE (p < 0.01). Importantly, for
      this single patient with the smaller tumor, 15.6% of the SE frames had >5 mm
      displacements from the ground truth vs 0% for DE fluoroscopy. CONCLUSIONS: This
      work indicates the potential for markerless tumor tracking utilizing DE
      fluoroscopy. With DE imaging, the algorithm showed improved detectability vs SE
      fluoroscopy and was able to accurately track the tumor in nearly all cases.

PMID- 25563266
TI  - The CNAO dose delivery system for modulated scanning ion beam radiotherapy.
AB  - PURPOSE: This paper describes the system for the dose delivery currently used at
      the Centro Nazionale di Adroterapia Oncologica (CNAO) for ion beam modulated
      scanning radiotherapy. METHODS: CNAO Foundation, Istituto Nazionale di Fisica
      Nucleare and University of Torino have designed, built, and commissioned a dose
      delivery system (DDS) to monitor and guide ion beams accelerated by a dedicated
      synchrotron and to distribute the dose with a full 3D scanning technique. Protons
      and carbon ions are provided for a wide range of energies in order to cover a
      sizable span of treatment depths. The target volume, segmented in several layers
      orthogonally to the beam direction, is irradiated by thousands of pencil beams
      which must be steered and held to the prescribed positions until the prescribed
      number of particles has been delivered. For the CNAO beam lines, these operations
      are performed by the DDS. The main components of this system are two independent
      beam monitoring detectors, called BOX1 and BOX2, interfaced with two control
      systems performing the tasks of real-time fast and slow control, and connected to
      the scanning magnets and the beam chopper. As a reaction to any condition leading
      to a potential hazard, a DDS interlock signal is sent to the patient interlock
      system which immediately stops the irradiation. The essential tasks and
      operations performed by the DDS are described following the data flow from the
      treatment planning system through the end of the treatment delivery. RESULTS: The
      ability of the DDS to guarantee a safe and accurate treatment was validated
      during the commissioning phase by means of checks of the charge collection
      efficiency, gain uniformity of the chambers, and 2D dose distribution homogeneity
      and stability. A high level of reliability and robustness has been proven by
      three years of system activity needing rarely more than regular maintenance and
      working with 100% uptime. Four identical and independent DDS devices have been
      tested showing comparable performances and are presently in use on the CNAO beam
      lines for clinical activity. CONCLUSIONS: The dose delivery system described in
      this paper is one among the few worldwide existing systems to operate ion beam
      for modulated scanning radiotherapy. At the time of writing, it has been used to
      treat more than 350 patients and it has proven to guide and control the
      therapeutic pencil beams reaching performances well above clinical requirements.
      In particular, in terms of dose accuracy and stability, daily quality assurance
      measurements have shown dose deviations always lower than the acceptance
      threshold of 5% and 2.5%, respectively.

PMID- 25563267
TI  - Commissioning the neutron production of a Linac: development of a simple tool for
      second cancer risk estimation.
AB  - PURPOSE: Knowing the contribution of neutron to collateral effects in treatments
      is both a complex and a mandatory task. This work aims to present an operative
      procedure for neutron estimates in any facility using a neutron digital detector.
      METHODS: The authors' previous work established a linear relationship between the
      total second cancer risk due to neutrons (TR(n)) and the number of MU of the
      treatment. Given that the digital detector also presents linearity with MU, its
      response can be used to determine the TR(n) per unit MU, denoted as m, normally
      associated to a generic Linac model and radiotherapy facility. Thus, from the
      number of MU of each patient treatment, the associated risk can be estimated. The
      feasibility of the procedure was tested by applying it in eight facilities;
      patients were evaluated as well. RESULTS: From the reading of the detector under
      selected irradiation conditions, m values were obtained for different machines,
      ranging from 0.25 * 10(-4)% per MU for an Elekta Axesse at 10 MV to 6.5 * 10(-4)%
      per MU for a Varian Clinac at 18 MV. Using these values, TR(n) of patients was
      estimated in each facility and compared to that from the individual evaluation.
      Differences were within the range of uncertainty of the authors' methodology of
      equivalent dose and risk estimations. CONCLUSIONS: The procedure presented here
      allows an easy estimation of the second cancer risk due to neutrons for any
      patient, given the number of MU of the treatment. It will enable the
      consideration of this information when selecting the optimal treatment for a
      patient by its implementation in the treatment planning system.

PMID- 25563268
TI  - Multienergy CT acquisition and reconstruction with a stepped tube potential scan.
AB  - PURPOSE: Based on an energy-dependent property of matter, one may obtain a
      pseudomonochromatic attenuation map, a material composition image, an electron
      density distribution, and an atomic number image using a dual- or multienergy
      computed tomography (CT) scan. Dual- and multienergy CT scans broaden the
      potential of x-ray CT imaging. The development of such systems is very useful in
      both medical and industrial investigations. In this paper, the authors propose a
      new dual- and multienergy CT system design (segmental multienergy CT, SegMECT)
      using an innovative scanning scheme that is conveniently implemented on a
      conventional single-energy CT system. The two-step-energy dual-energy CT can be
      regarded as a special case of SegMECT. A special reconstruction method is
      proposed to support SegMECT. METHODS: In their SegMECT, a circular trajectory in
      a CT scan is angularly divided into several arcs. The x-ray source is set to a
      different tube voltage for each arc of the trajectory. Thus, the authors only
      need to make a few step changes to the x-ray energy during the scan to complete a
      multienergy data acquisition. With such a data set, the image reconstruction
      might suffer from severe limited-angle artifacts if using conventional
      reconstruction methods. To solve the problem, they present a new prior-image
      based reconstruction technique using a total variance norm of a quotient image
      constraint. On the one hand, the prior extracts structural information from all
      of the projection data. On the other hand, the effect from a possibly imprecise
      intensity level of the prior can be mitigated by minimizing the total variance of
      a quotient image. RESULTS: The authors present a new scheme for a SegMECT
      configuration and establish a reconstruction method for such a system. Both
      numerical simulation and a practical phantom experiment are conducted to validate
      the proposed reconstruction method and the effectiveness of the system design.
      The results demonstrate that the proposed SegMECT can provide both attenuation
      images and material decomposition images of reasonable image quality. Compared to
      existing methods, the new system configuration demonstrates advantages in
      simplicity of implementation, system cost, and dose control. CONCLUSIONS: This
      proposed SegMECT imaging approach has great potential for practical applications.
      It can be readily realized on a conventional CT system.

PMID- 25563269
TI  - Characterization of the Exradin W1 scintillator for use in radiotherapy.
AB  - PURPOSE: To evaluate the main characteristics of the Exradin W1 scintillator as a
      dosimeter and to estimate measurement uncertainties when used in radiotherapy.
      METHODS: We studied the calibration procedure, energy and modality dependence,
      short-term repeatability, dose-response linearity, angular dependence,
      temperature dependence, time to reach thermal equilibrium, dose-rate dependence,
      water-equivalent depth of the effective measurement point, and long-term
      stability. An uncertainty budget was derived for relative and absolute dose
      measurements in photon and electron beams. RESULTS: Exradin W1 showed a
      temperature dependence of -0.225%  degrees C(-1). The loss of sensitivity with
      accumulated dose decreased with use. The sensitivity of Exradin W1 was energy
      independent for high-energy photon and electron beams. All remaining dependencies
      of Exradin W1 were around or below 0.5%, leading to an uncertainty budget of
      about 1%. When a dual channel electrometer with automatic trigger was not used,
      timing effects became significant, increasing uncertainties by one order of
      magnitude. CONCLUSIONS: The Exradin W1 response is energy independent for high
      energy x-rays and electron beams, and only one calibration coefficient is needed.
      A temperature correction factor should be applied to keep uncertainties around 2%
      for absolute dose measurements and around 1% for relative measurements in high
      energy photon and electron beams. The Exradin W1 scintillator is an excellent
      alternative to detectors such as diodes for relative dose measurements.

PMID- 25563270
TI  - Thermal regulation of tightly packed solid-state photodetectors in a 1 mm(3)
      resolution clinical PET system.
AB  - PURPOSE: Silicon photodetectors are of significant interest for use in positron
      emission tomography (PET) systems due to their compact size, insensitivity to
      magnetic fields, and high quantum efficiency. However, one of their main
      disadvantages is fluctuations in temperature cause strong shifts in gain of the
      devices. PET system designs with high photodetector density suffer both increased
      thermal density and constrained options for thermally regulating the devices.
      This paper proposes a method of thermally regulating densely packed silicon
      photodetectors in the context of a 1 mm(3) resolution, high-sensitivity PET
      camera dedicated to breast imaging. METHODS: The PET camera under construction
      consists of 2304 units, each containing two 8 * 8 arrays of 1 mm(3) LYSO crystals
      coupled to two position sensitive avalanche photodiodes (PSAPD). A subsection of
      the proposed camera with 512 PSAPDs has been constructed. The proposed thermal
      regulation design uses water-cooled heat sinks, thermoelectric elements, and
      thermistors to measure and regulate the temperature of the PSAPDs in a novel
      manner. Active cooling elements, placed at the edge of the detector stack due to
      limited access, are controlled based on collective leakage current and
      temperature measurements in order to keep all the PSAPDs at a consistent
      temperature. This thermal regulation design is characterized for the temperature
      profile across the camera and for the time required for cooling changes to
      propagate across the camera. These properties guide the implementation of a
      software-based, cascaded proportional-integral-derivative control loop that
      controls the current through the Peltier elements by monitoring thermistor
      temperature and leakage current. The stability of leakage current, temperature
      within the system using this control loop is tested over a period of 14 h. The
      energy resolution is then measured over a period of 8.66 h. Finally, the
      consistency of PSAPD gain between independent operations of the camera over 10
      days is tested. RESULTS: The PET camera maintains a temperature of 18.00 +/- 0.05
      degrees C over the course of 12 h while the ambient temperature varied 0.61 
      degrees C, from 22.83 to 23.44  degrees C. The 511 keV photopeak energy
      resolution over a period of 8.66 h is measured to be 11.3% FWHM with a maximum
      photopeak fluctuation of 4 keV. Between measurements of PSAPD gain separated by
      at least 2 day, the maximum photopeak shift was 6 keV. CONCLUSIONS: The proposed
      thermal regulation scheme for tightly packed silicon photodetectors provides for
      stable operation of the constructed subsection of a PET camera over long
      durations of time. The energy resolution of the system is not degraded despite
      shifts in ambient temperature and photodetector heat generation. The thermal
      regulation scheme also provides a consistent operating environment between
      separate runs of the camera over different days. Inter-run consistency allows for
      reuse of system calibration parameters from study to study, reducing the time
      required to calibrate the system and hence to obtain a reconstructed image.

PMID- 25563271
TI  - Assessment of the dose reduction potential of a model-based iterative
      reconstruction algorithm using a task-based performance metrology.
AB  - PURPOSE: Different computed tomography (CT) reconstruction techniques offer
      different image quality attributes of resolution and noise, challenging the
      ability to compare their dose reduction potential against each other. The purpose
      of this study was to evaluate and compare the task-based imaging performance of
      CT systems to enable the assessment of the dose performance of a model-based
      iterative reconstruction (MBIR) to that of an adaptive statistical iterative
      reconstruction (ASIR) and a filtered back projection (FBP) technique. METHODS:
      The ACR CT phantom (model 464) was imaged across a wide range of mA setting on a
      64-slice CT scanner (GE Discovery CT750 HD, Waukesha, WI). Based on previous
      work, the resolution was evaluated in terms of a task-based modulation transfer
      function (MTF) using a circular-edge technique and images from the contrast
      inserts located in the ACR phantom. Noise performance was assessed in terms of
      the noise-power spectrum (NPS) measured from the uniform section of the phantom.
      The task-based MTF and NPS were combined with a task function to yield a task
      based estimate of imaging performance, the detectability index (d'). The
      detectability index was computed as a function of dose for two imaging tasks
      corresponding to the detection of a relatively small and a relatively large
      feature (1.5 and 25 mm, respectively). The performance of MBIR in terms of the d'
      was compared with that of ASIR and FBP to assess its dose reduction potential.
      RESULTS: Results indicated that MBIR exhibits a variability spatial resolution
      with respect to object contrast and noise while significantly reducing image
      noise. The NPS measurements for MBIR indicated a noise texture with a low-pass
      quality compared to the typical midpass noise found in FBP-based CT images. At
      comparable dose, the d' for MBIR was higher than those of FBP and ASIR by at
      least 61% and 19% for the small feature and the large feature tasks,
      respectively. Compared to FBP and ASIR, MBIR indicated a 46%-84% dose reduction
      potential, depending on task, without compromising the modeled detection
      performance. CONCLUSIONS: The presented methodology based on ACR phantom
      measurements extends current possibilities for the assessment of CT image quality
      under the complex resolution and noise characteristics exhibited with statistical
      and iterative reconstruction algorithms. The findings further suggest that MBIR
      can potentially make better use of the projections data to reduce CT dose by
      approximately a factor of 2. Alternatively, if the dose held unchanged, it can
      improve image quality by different levels for different tasks.

PMID- 25563272
TI  - Quantifying the impact of respiratory-gated 4D CT acquisition on thoracic image
      quality: a digital phantom study.
AB  - PURPOSE: Prospective respiratory-gated 4D CT has been shown to reduce tumor image
      artifacts by up to 50% compared to conventional 4D CT. However, to date no
      studies have quantified the impact of gated 4D CT on normal lung tissue imaging,
      which is important in performing dose calculations based on accurate estimates of
      lung volume and structure. To determine the impact of gated 4D CT on thoracic
      image quality, the authors developed a novel simulation framework incorporating a
      realistic deformable digital phantom driven by patient tumor motion patterns.
      Based on this framework, the authors test the hypothesis that respiratory-gated
      4D CT can significantly reduce lung imaging artifacts. METHODS: Our simulation
      framework synchronizes the 4D extended cardiac torso (XCAT) phantom with tumor
      motion data in a quasi real-time fashion, allowing simulation of three 4D CT
      acquisition modes featuring different levels of respiratory feedback: (i)
      "conventional" 4D CT that uses a constant imaging and couch-shift frequency, (ii)
      "beam paused" 4D CT that interrupts imaging to avoid oversampling at a given
      couch position and respiratory phase, and (iii) "respiratory-gated" 4D CT that
      triggers acquisition only when the respiratory motion fulfills phase-specific
      displacement gating windows based on prescan breathing data. Our framework
      generates a set of ground truth comparators, representing the average XCAT
      anatomy during beam-on for each of ten respiratory phase bins. Based on this
      framework, the authors simulated conventional, beam-paused, and respiratory-gated
      4D CT images using tumor motion patterns from seven lung cancer patients across
      13 treatment fractions, with a simulated 5.5 cm(3) spherical lesion. Normal lung
      tissue image quality was quantified by comparing simulated and ground truth
      images in terms of overall mean square error (MSE) intensity difference,
      threshold-based lung volume error, and fractional false positive/false negative
      rates. RESULTS: Averaged across all simulations and phase bins, respiratory
      gating reduced overall thoracic MSE by 46% compared to conventional 4D CT (p ~
      10(-19)). Gating leads to small but significant (p < 0.02) reductions in lung
      volume errors (1.8%-1.4%), false positives (4.0%-2.6%), and false negatives (2.7%
      1.3%). These percentage reductions correspond to gating reducing image artifacts
      by 24-90 cm(3) of lung tissue. Similar to earlier studies, gating reduced patient
      image dose by up to 22%, but with scan time increased by up to 135%. Beam paused
      4D CT did not significantly impact normal lung tissue image quality, but did
      yield similar dose reductions as for respiratory-gating, without the added cost
      in scanning time. CONCLUSIONS: For a typical 6 L lung, respiratory-gated 4D CT
      can reduce image artifacts affecting up to 90 cm(3) of normal lung tissue
      compared to conventional acquisition. This image improvement could have important
      implications for dose calculations based on 4D CT. Where image quality is less
      critical, beam paused 4D CT is a simple strategy to reduce imaging dose without
      sacrificing acquisition time.

PMID- 25563273
TI  - Position tracking of moving liver lesion based on real-time registration between
      2D ultrasound and 3D preoperative images.
AB  - PURPOSE: Registration between 2D ultrasound (US) and 3D preoperative magnetic
      resonance (MR) (or computed tomography, CT) images has been studied recently for
      US-guided intervention. However, the existing techniques have some limits, either
      in the registration speed or the performance. The purpose of this work is to
      develop a real-time and fully automatic registration system between two
      intermodal images of the liver, and subsequently an indirect lesion
      positioning/tracking algorithm based on the registration result, for image-guided
      interventions. METHODS: The proposed position tracking system consists of three
      stages. In the preoperative stage, the authors acquire several 3D preoperative MR
      (or CT) images at different respiratory phases. Based on the transformations
      obtained from nonrigid registration of the acquired 3D images, they then generate
      a 4D preoperative image along the respiratory phase. In the intraoperative
      preparatory stage, they properly attach a 3D US transducer to the patient's body
      and fix its pose using a holding mechanism. They then acquire a couple of
      respiratory-controlled 3D US images. Via the rigid registration of these US
      images to the 3D preoperative images in the 4D image, the pose information of the
      fixed-pose 3D US transducer is determined with respect to the preoperative image
      coordinates. As feature(s) to use for the rigid registration, they may choose
      either internal liver vessels or the inferior vena cava. Since the latter is
      especially useful in patients with a diffuse liver disease, the authors newly
      propose using it. In the intraoperative real-time stage, they acquire 2D US
      images in real-time from the fixed-pose transducer. For each US image, they
      select candidates for its corresponding 2D preoperative slice from the 4D
      preoperative MR (or CT) image, based on the predetermined pose information of the
      transducer. The correct corresponding image is then found among those candidates
      via real-time 2D registration based on a gradient-based similarity measure.
      Finally, if needed, they obtain the position information of the liver lesion
      using the 3D preoperative image to which the registered 2D preoperative slice
      belongs. RESULTS: The proposed method was applied to 23 clinical datasets and
      quantitative evaluations were conducted. With the exception of one clinical
      dataset that included US images of extremely low quality, 22 datasets of various
      liver status were successfully applied in the evaluation. Experimental results
      showed that the registration error between the anatomical features of US and
      preoperative MR images is less than 3 mm on average. The lesion tracking error
      was also found to be less than 5 mm at maximum. CONCLUSIONS: A new system has
      been proposed for real-time registration between 2D US and successive multiple 3D
      preoperative MR/CT images of the liver and was applied for indirect lesion
      tracking for image-guided intervention. The system is fully automatic and robust
      even with images that had low quality due to patient status. Through visual
      examinations and quantitative evaluations, it was verified that the proposed
      system can provide high lesion tracking accuracy as well as high registration
      accuracy, at performance levels which were acceptable for various clinical
      applications.

PMID- 25563275
TI  - The first clinical treatment with kilovoltage intrafraction monitoring (KIM): a
      real-time image guidance method.
AB  - PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a real-time image guidance
      method that uses widely available radiotherapy technology, i.e., a gantry-mounted
      x-ray imager. The authors report on the geometric and dosimetric results of the
      first patient treatment using KIM which occurred on September 16, 2014. METHODS:
      KIM uses current and prior 2D x-ray images to estimate the 3D target position
      during cancer radiotherapy treatment delivery. KIM software was written to
      process kilovoltage (kV) images streamed from a standard C-arm linear accelerator
      with a gantry-mounted kV x-ray imaging system. A 120 degrees  pretreatment kV
      imaging arc was acquired to build the patient-specific 2D to 3D motion
      correlation. The kV imager was activated during the megavoltage (MV) treatment, a
      dual arc VMAT prostate treatment, to estimate the 3D prostate position in real
      time. All necessary ethics, legal, and regulatory requirements were met for this
      clinical study. The quality assurance processes were completed and peer reviewed.
      RESULTS: During treatment, a prostate position offset of nearly 3 mm in the
      posterior direction was observed with KIM. This position offset did not trigger a
      gating event. After the treatment, the prostate motion was independently measured
      using kV/MV triangulation, resulting in a mean difference of less than 0.6 mm and
      standard deviation of less than 0.6 mm in each direction. The accuracy of the
      marker segmentation was visually assessed during and after treatment and found to
      be performing well. During treatment, there were no interruptions due to
      performance of the KIM software. CONCLUSIONS: For the first time, KIM has been
      used for real-time image guidance during cancer radiotherapy. The measured
      accuracy and precision were both submillimeter for the first treatment fraction.
      This clinical translational research milestone paves the way for the broad
      implementation of real-time image guidance to facilitate the detection and
      correction of geometric and dosimetric errors, and resultant improved clinical
      outcomes, in cancer radiotherapy.

PMID- 25563274
TI  - Novel tools for stepping source brachytherapy treatment planning: enhanced
      geometrical optimization and interactive inverse planning.
AB  - PURPOSE: Dose optimization for stepping source brachytherapy can nowadays be
      performed using automated inverse algorithms. Although much quicker than
      graphical optimization, an experienced treatment planner is required for both
      methods. With automated inverse algorithms, the procedure to achieve the desired
      dose distribution is often based on trial-and-error. METHODS: A new approach for
      stepping source prostate brachytherapy treatment planning was developed as a
      quick and user-friendly alternative. This approach consists of the combined use
      of two novel tools: Enhanced geometrical optimization (EGO) and interactive
      inverse planning (IIP). EGO is an extended version of the common geometrical
      optimization method and is applied to create a dose distribution as homogeneous
      as possible. With the second tool, IIP, this dose distribution is tailored to a
      specific patient anatomy by interactively changing the highest and lowest dose on
      the contours. RESULTS: The combined use of EGO-IIP was evaluated on 24 prostate
      cancer patients, by having an inexperienced user create treatment plans,
      compliant to clinical dose objectives. This user was able to create dose plans of
      24 patients in an average time of 4.4 min/patient. An experienced treatment
      planner without extensive training in EGO-IIP also created 24 plans. The
      resulting dose-volume histogram parameters were comparable to the clinical plans
      and showed high conformance to clinical standards. CONCLUSIONS: Even for an
      inexperienced user, treatment planning with EGO-IIP for stepping source prostate
      brachytherapy is feasible as an alternative to current optimization algorithms,
      offering speed, simplicity for the user, and local control of the dose levels.

PMID- 25563277
TI  - Planar strain analysis of liver undergoing microwave thermal ablation using x-ray
      CT.
AB  - PURPOSE: To study the planar strain effects in liver during microwave (MW)
      thermal ablation as a means for tracking tissue expansion and contraction as a
      method for improving ablation monitoring. METHODS: 1.4 mm circular metallic
      markers were inserted into 16 ex-vivo bovine fresh liver specimens, that were
      subsequently ablated (with the markers inside the specimen) by 40 W of microwave
      energy, for 1, 2, 3, 6, and 10 min. The markers were tracked during the ablation
      using an x-ray CT scanner. Images were acquired every 5-10 s enabling
      determination of the markers' coordinates over time. The 2D principal strains
      were calculated for triangles formed by subgroups of three markers, and their
      planar strain index, Omega, was plotted vs time. In addition, the radial distance
      of the markers from the antenna was measured at the end of each ablation.
      Subsequently, the tissue was sliced parallel to the imaged planes and the
      ablation zone was traced and digitized. The average ablation radius was then
      computed and compared to the radial distance. RESULTS: The planar strain,
      Omega(t), profile demonstrated an ascending pattern until reaching a maximum at
      about 180 s, with a mean peak value (Omega = 1.31 +/- 0.04) indicating tissue
      expansion. Thereafter, Omega progressively declined over the remaining duration
      of the ablation treatment, indicating tissue contraction. Furthermore, when
      plotting the ablation size vs time and the markers' mean radial distance vs time,
      it was found that the two curves intercepted at a time corresponding to the time
      of peak planar strain. CONCLUSIONS: By detecting the point of maximal planar
      strain in tissues during MW application, it is possible to noninvasively identify
      the location of the ablation zone front. The fact that the liver tissue proximal
      to the ablated zone expands during the first part of the treatment and then
      contracts when the ablation front reaches it, may serve as an index for
      monitoring the thermal treatment.

PMID- 25563276
TI  - Parallel transmit excitation at 1.5 T based on the minimization of a driving
      function for device heating.
AB  - PURPOSE: To provide a rapid method to reduce the radiofrequency (RF) E-field
      coupling and consequent heating in long conductors in an interventional MRI
      (iMRI) setup. METHODS: A driving function for device heating (W) was defined as
      the integration of the E-field along the direction of the wire and calculated
      through a quasistatic approximation. Based on this function, the phases of four
      independently controlled transmit channels were dynamically changed in a 1.5 T
      MRI scanner. During the different excitation configurations, the RF induced
      heating in a nitinol wire immersed in a saline phantom was measured by fiber
      optic temperature sensing. Additionally, a minimization of W as a function of
      phase and amplitude values of the different channels and constrained by the
      homogeneity of the RF excitation field (B1) over a region of interest was
      proposed and its results tested on the benchtop. To analyze the validity of the
      proposed method, using a model of the array and phantom setup tested in the
      scanner, RF fields and SAR maps were calculated through finite-difference time
      domain (FDTD) simulations. In addition to phantom experiments, RF induced heating
      of an active guidewire inserted in a swine was also evaluated. RESULTS: In the
      phantom experiment, heating at the tip of the device was reduced by 92% when
      replacing the body coil by an optimized parallel transmit excitation with same
      nominal flip angle. In the benchtop, up to 90% heating reduction was measured
      when implementing the constrained minimization algorithm with the additional
      degree of freedom given by independent amplitude control. The computation of the
      optimum phase and amplitude values was executed in just 12 s using a standard
      CPU. The results of the FDTD simulations showed similar trend of the local SAR at
      the tip of the wire and measured temperature as well as to a quadratic function
      of W, confirming the validity of the quasistatic approach for the presented
      problem at 64 MHz. Imaging and heating reduction of the guidewire were
      successfully performed in vivo with the proposed hardware and phase control.
      CONCLUSIONS: Phantom and in vivo data demonstrated that additional degrees of
      freedom in a parallel transmission system can be used to control RF induced
      heating in long conductors. A novel constrained optimization approach to reduce
      device heating was also presented that can be run in just few seconds and
      therefore could be added to an iMRI protocol to improve RF safety.

PMID- 25563278
TI  - Quality assurance for online adapted treatment plans: benchmarking and delivery
      monitoring simulation.
AB  - PURPOSE: An important challenge facing online adaptive radiation therapy is the
      development of feasible and efficient quality assurance (QA). This project aimed
      to validate the deliverability of online adapted plans and develop a proof-of
      concept online delivery monitoring system for online adaptive radiation therapy
      QA. METHODS: The first part of this project benchmarked automatically online
      adapted prostate treatment plans using traditional portal dosimetry IMRT QA. The
      portal dosimetry QA results of online adapted plans were compared to original
      (unadapted) plans as well as randomly selected prostate IMRT plans from our
      clinic. In the second part, an online delivery monitoring system was designed and
      validated via a simulated treatment with intentional multileaf collimator (MLC)
      errors. This system was based on inputs from the dynamic machine information
      (DMI), which continuously reports actual MLC positions and machine monitor units
      (MUs) at intervals of 50 ms or less during delivery. Based on the DMI, the system
      performed two levels of monitoring/verification during the delivery: (1) dynamic
      monitoring of cumulative fluence errors resulting from leaf position deviations
      and visualization using fluence error maps (FEMs); and (2) verification of MLC
      positions against the treatment plan for potential errors in MLC motion and data
      transfer at each control point. Validation of the online delivery monitoring
      system was performed by introducing intentional systematic MLC errors (ranging
      from 0.5 to 2 mm) to the DMI files for both leaf banks. These DMI files were
      analyzed by the proposed system to evaluate the system's performance in
      quantifying errors and revealing the source of errors, as well as to understand
      patterns in the FEMs. In addition, FEMs from 210 actual prostate IMRT beams were
      analyzed using the proposed system to further validate its ability to catch and
      identify errors, as well as establish error magnitude baselines for prostate IMRT
      delivery. RESULTS: Online adapted plans were found to have similar delivery
      accuracy in comparison to clinical IMRT plans when validated with portal
      dosimetry IMRT QA. FEMs for the simulated deliveries with intentional MLC errors
      exhibited distinct patterns for different MLC error magnitudes and directions,
      indicating that the proposed delivery monitoring system is highly specific in
      detecting the source of errors. Implementing the proposed QA system for online
      adapted plans revealed excellent delivery accuracy: over 99% of leaf position
      differences were within 0.5 mm, and >99% of pixels in the FEMs had fluence errors
      within 0.5 MU. Patterns present in the FEMs and MLC control point analysis for
      actual patient cases agreed with the error pattern analysis results, further
      validating the system's ability to reveal and differentiate MLC deviations.
      Calculation of the fluence map based on the DMI was performed within 2 ms after
      receiving each DMI input. CONCLUSIONS: The proposed online delivery monitoring
      system requires minimal additional resources and time commitment to the current
      clinical workflow while still maintaining high sensitivity to leaf position
      errors and specificity to error types. The presented online delivery monitoring
      system therefore represents a promising QA system candidate for online adaptive
      radiation therapy.

PMID- 25563279
TI  - Effect of deformable registration on the dose calculated in radiation therapy
      planning CT scans of lung cancer patients.
AB  - PURPOSE: To characterize the effects of deformable image registration of serial
      computed tomography (CT) scans on the radiation dose calculated from a treatment
      planning scan. METHODS: Eighteen patients who received curative doses (>= 60 Gy,
      2 Gy/fraction) of photon radiation therapy for lung cancer treatment were
      retrospectively identified. For each patient, a diagnostic-quality pretherapy (4
      75 days) CT scan and a treatment planning scan with an associated dose map were
      collected. To establish correspondence between scan pairs, a researcher manually
      identified anatomically corresponding landmark point pairs between the two scans.
      Pretherapy scans then were coregistered with planning scans (and associated dose
      maps) using the demons deformable registration algorithm and two variants of the
      Fraunhofer MEVIS algorithm ("Fast" and "EMPIRE10"). Landmark points in each
      pretherapy scan were automatically mapped to the planning scan using the
      displacement vector field output from each of the three algorithms. The Euclidean
      distance between manually and automatically mapped landmark points (dE) and the
      absolute difference in planned dose (|DeltaD|) were calculated. Using regression
      modeling, |DeltaD| was modeled as a function of dE, dose (D), dose standard
      deviation (SD(dose)) in an eight-pixel neighborhood, and the registration
      algorithm used. RESULTS: Over 1400 landmark point pairs were identified, with 58
      93 (median: 84) points identified per patient. Average |DeltaD| across patients
      was 3.5 Gy (range: 0.9-10.6 Gy). Registration accuracy was highest using the
      Fraunhofer MEVIS EMPIRE10 algorithm, with an average dE across patients of 5.2 mm
      (compared with >7 mm for the other two algorithms). Consequently, average
      |DeltaD| was also lowest using the Fraunhofer MEVIS EMPIRE10 algorithm. |DeltaD|
      increased significantly as a function of dE (0.42 Gy/mm), D (0.05 Gy/Gy),
      SD(dose) (1.4 Gy/Gy), and the algorithm used (<= 1 Gy). CONCLUSIONS: An average
      error of <4 Gy in radiation dose was introduced when points were mapped between
      CT scan pairs using deformable registration, with the majority of points yielding
      dose-mapping error <2 Gy (approximately 3% of the total prescribed dose).
      Registration accuracy was highest using the Fraunhofer MEVIS EMPIRE10 algorithm,
      resulting in the smallest errors in mapped dose. Dose differences following
      registration increased significantly with increasing spatial registration errors,
      dose, and dose gradient (i.e., SDdose). This model provides a measurement of the
      uncertainty in the radiation dose when points are mapped between serial CT scans
      through deformable registration.

PMID- 25563280
TI  - The alanine detector in BNCT dosimetry: dose response in thermal and epithermal
      neutron fields.
AB  - PURPOSE: The response of alanine solid state dosimeters to ionizing radiation
      strongly depends on particle type and energy. Due to nuclear interactions,
      neutron fields usually also consist of secondary particles such as photons and
      protons of diverse energies. Various experiments have been carried out in three
      different neutron beams to explore the alanine dose response behavior and to
      validate model predictions. Additionally, application in medical neutron fields
      for boron neutron capture therapy is discussed. METHODS: Alanine detectors have
      been irradiated in the thermal neutron field of the research reactor TRIGA Mainz,
      Germany, in five experimental conditions, generating different secondary particle
      spectra. Further irradiations have been made in the epithermal neutron beams at
      the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor
      in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance
      spectrometry with reference to an absorbed dose standard in a (60)Co gamma ray
      beam. Absorbed doses and dose components have been calculated using the Monte
      Carlo codes fluka and mcnp. The relative effectiveness (RE), linking absorbed
      dose and detector response, has been calculated using the Hansen & Olsen alanine
      response model. RESULTS: The measured dose response of the alanine detector in
      the different experiments has been evaluated and compared to model predictions.
      Therefore, a relative effectiveness has been calculated for each dose component,
      accounting for its dependence on particle type and energy. Agreement within 5%
      between model and measurement has been achieved for most irradiated detectors.
      Significant differences have been observed in response behavior between thermal
      and epithermal neutron fields, especially regarding dose composition and depth
      dose curves. The calculated dose components could be verified with the
      experimental results in the different primary and secondary particle fields.
      CONCLUSIONS: The alanine detector can be used without difficulty in neutron
      fields. The response has been understood with the model used which includes the
      relative effectiveness. Results and the corresponding discussion lead to the
      conclusion that application in neutron fields for medical purpose is limited by
      its sensitivity but that it is a useful tool as supplement to other detectors and
      verification of neutron source descriptions.

PMID- 25563281
TI  - HDR 192Ir source speed measurements using a high speed video camera.
AB  - PURPOSE: The dose delivered with a HDR (192)Ir afterloader can be separated into
      a dwell component, and a transit component resulting from the source movement.
      The transit component is directly dependent on the source speed profile and it is
      the goal of this study to measure accurate source speed profiles. METHODS: A high
      speed video camera was used to record the movement of a (192)Ir source
      (Nucletron, an Elekta company, Stockholm, Sweden) for interdwell distances of
      0.25-5 cm with dwell times of 0.1, 1, and 2 s. Transit dose distributions were
      calculated using a Monte Carlo code simulating the source movement. RESULTS: The
      source stops at each dwell position oscillating around the desired position for a
      duration up to (0.026 +/- 0.005) s. The source speed profile shows variations
      between 0 and 81 cm/s with average speed of ~ 33 cm/s for most of the interdwell
      distances. The source stops for up to (0.005 +/- 0.001) s at nonprogrammed
      positions in between two programmed dwell positions. The dwell time correction
      applied by the manufacturer compensates the transit dose between the dwell
      positions leading to a maximum overdose of 41 mGy for the considered cases and
      assuming an air-kerma strength of 48 000 U. The transit dose component is not
      uniformly distributed leading to over and underdoses, which is within 1.4% for
      commonly prescribed doses (3-10 Gy). CONCLUSIONS: The source maintains its speed
      even for the short interdwell distances. Dose variations due to the transit dose
      component are much lower than the prescribed treatment doses for brachytherapy,
      although transit dose component should be evaluated individually for clinical
      cases.

PMID- 25563282
TI  - Correcting lateral response artifacts from flatbed scanners for radiochromic film
      dosimetry.
AB  - PURPOSE: A known factor affecting the accuracy of radiochromic film dosimetry is
      the lateral response artifact (LRA) induced by nonuniform response of a flatbed
      scanner in the direction perpendicular to the scan direction. This work reports a
      practical solution to eliminate such artifacts for all forms of dose QA. METHODS:
      EBT3 films from a single production lot (02181401) cut into rectangular 4 * 5
      cm(2) pieces, with the long dimension parallel to the long dimension of the
      original 20.3 * 25.4 cm(2) sheets, were exposed at a depth of 5 cm on a Varian
      Trilogy at the center of a 20 * 20 cm(2) open field at seven doses between 50 and
      1600 cGy using 6 MV photons. These films together with an unexposed film from the
      same production lot were lined one next to the other on an Epson 10000 XL or
      11000 XL scanner in portrait orientation with their long dimension parallel to
      the scan direction. Scanned images were then obtained with the line of films
      positioned at seven discrete lateral locations perpendicular to the scan
      direction. The process was repeated in landscape orientation and on three other
      Epson scanners. Data were also collected for three additional production lots of
      EBT3 film (11051302, 03031401, and 03171403). From measurements at the various
      lateral positions, the scanner response was determined as a function of the
      lateral position of the scanned film. For a given color channel X, the response
      at any lateral position L is related to the response at the center, C, of the
      scanner by Response(C, D, X) = A(L,X) + B(L,X) ? Response(L, D, X), where D is
      dose and the coefficients A(L,X) and B(L,X) are determined from the film
      measurements at the center of the scanner and six other discrete lateral
      positions. The values at intermediate lateral positions were obtained by linear
      interpolation. The coefficients were determined for the red, green, and blue
      color channels, preserving the ability to apply triple-channel dosimetry once
      corrections were applied to compensate for the lateral position response
      artifact. To validate this method, corrections were applied to several films that
      were exposed to 15 * 15 cm(2) open fields and large IMRT and VMAT fields and
      scanned at the extreme edges of the scan window in addition to the central
      location. Calibration and response data were used to generate dose maps and
      perform gamma analysis using single- or triple-channel dosimetry with FilmQAPro
      2014 software. RESULTS: The authors' study found that calibration curves at the
      different lateral positions could be correlated by a simple two-point rescaling
      using the response for unexposed film as well as the response of film exposed at
      high doses between 800 and 1600 cGy. The coefficients A(L,X) and BL,X for each
      color channel X were found to be independent of dose at each lateral location L.
      This made it possible to apply the relationship Response(C, D, X) = A(L,X) +
      B(L,X) ? Response(L, D, X), to the raw film responses, permitting correction of
      the response values at any lateral position to an equivalent response, as if that
      part of the film was located at the center of the scanner. This correction method
      was validated for several films exposed to open as well as large IMRT and VMAT
      fields. CONCLUSIONS: The work reported elaborates on the process using the
      correction procedures to eliminate the lateral response artifact and demonstrates
      improvements in the accuracy of radiochromic film dosimetry for the radiation
      therapy quality assurance applications.

PMID- 25563283
TI  - The targeting accuracy of a preclinical MRI-guided focused ultrasound system.
AB  - PURPOSE: Assess the accuracy, precision, and sources of error using a preclinical
      MR-guided focused ultrasound system. METHODS: A preclinical focused ultrasound
      system, described previously [Chopra et al., Med. Phys. 36(5), 1867-1874 (2009)],
      was tested on a benchtop and with 3T GE, 3T Philips, and 7 T Bruker MR scanners
      for spatial targeting accuracy and precision. Randomly distributed water-filled
      holes drilled into a polystyrene plate were imaged using MRI and targeted using
      treatment planning software. The ultrasound focus of a 72 mm, f-number 0.8, 1.16
      MHz transducer was aimed at the target locations, and 1-2 s continuous-wave
      sonications were performed on clear polystyrene plates to create localized spots
      of melted plastic. The distance between target and observed locations was
      measured and analyzed. Retrospective analysis of targeting accuracy was performed
      on preclinical data obtained from other experiments at their institution using
      the same system. RESULTS: The results suggest that the sources of targeting error
      under MR guidance can be roughly separated into three components--normally
      distributed random error; constant shift from inaccuracy in detection of the
      initial ultrasound focus; and angular misalignment between MR and focused
      ultrasound (FUS) coordinates. The lower bound on the targeting error was
      estimated to be 0.25 +/- 0.13 mm, while the maximum observed targeting error did
      not exceed 2 mm. Measures required to reduce errors and improve targeting were
      developed to reduce the registration and misalignment errors such that maximum
      error was reduced to 0.36 +/- 0.14 mm. Retrospective in vivo analysis indicated
      that the error was 1.02 +/- 0.43 mm, including error extrinsic to the system.
      CONCLUSIONS: The FUS system, as described, is capable of precise and accurate
      sonications. The largest source of error--misregistration of the coordinate
      systems of the scanner and ultrasound system--was addressed which reduced the
      error to 0.36 +/- 0.14 mm, sufficient for many preclinical applications.

PMID- 25563284
TI  - Ultraviolet radiation therapy and UVR dose models.
AB  - Ultraviolet radiation (UVR) has been an effective treatment for a number of
      chronic skin disorders, and its ability to alleviate these conditions has been
      well documented. Although nonionizing, exposure to ultraviolet (UV) radiation is
      still damaging to deoxyribonucleic acid integrity, and has a number of unpleasant
      side effects ranging from erythema (sunburn) to carcinogenesis. As the conditions
      treated with this therapy tend to be chronic, exposures are repeated and can be
      high, increasing the lifetime probability of an adverse event or mutagenic
      effect. Despite the potential detrimental effects, quantitative ultraviolet
      dosimetry for phototherapy is an underdeveloped area and better dosimetry would
      allow clinicians to maximize biological effect whilst minimizing the
      repercussions of overexposure. This review gives a history and insight into the
      current state of UVR phototherapy, including an overview of biological effects of
      UVR, a discussion of UVR production, illness treated by this modality, cabin
      design and the clinical implementation of phototherapy, as well as clinical dose
      estimation techniques. Several dose models for ultraviolet phototherapy are also
      examined, and the need for an accurate computational dose estimation method in
      ultraviolet phototherapy is discussed. 

PMID- 25563285
TI  - A mitral annulus tracking approach for navigation of off-pump beating heart
      mitral valve repair.
AB  - PURPOSE: To develop and validate a real-time mitral valve annulus (MVA) tracking
      approach based on biplane transesophageal echocardiogram (TEE) data and magnetic
      tracking systems (MTS) to be used in minimally invasive off-pump beating heart
      mitral valve repair (MVR). METHODS: The authors' guidance system consists of
      three major components: TEE, magnetic tracking system, and an image guidance
      software platform. TEE provides real-time intraoperative images to show the
      cardiac motion and intracardiac surgical tools. The magnetic tracking system
      tracks the TEE probe and the surgical tools. The software platform integrates the
      TEE image planes and the virtual model of the tools and the MVA model on the
      screen. The authors' MVA tracking approach, which aims to update the MVA model in
      near real-time, comprises of three steps: image based gating, predictive
      reinitialization, and registration based MVA tracking. The image based gating
      step uses a small patch centered at each MVA point in the TEE images to identify
      images at optimal cardiac phases for updating the position of the MVA. The
      predictive reinitialization step uses the position and orientation of the TEE
      probe provided by the magnetic tracking system to predict the position of the MVA
      points in the TEE images and uses them for the initialization of the registration
      component. The registration based MVA tracking step aims to locate the MVA points
      in the images selected by the image based gating component by performing image
      based registration. RESULTS: The validation of the MVA tracking approach was
      performed in a phantom study and a retrospective study on porcine data. In the
      phantom study, controlled translations were applied to the phantom and the
      tracked MVA was compared to its "true" position estimated based on a magnetic
      sensor attached to the phantom. The MVA tracking accuracy was 1.29 +/- 0.58 mm
      when the translation distance is about 1 cm, and increased to 2.85 +/- 1.19 mm
      when the translation distance is about 3 cm. In the study on porcine data, the
      authors compared the tracked MVA to a manually segmented MVA. The overall
      accuracy is 2.37 +/- 1.67 mm for single plane images and 2.35 +/- 1.55 mm for
      biplane images. The interoperator variation in manual segmentation was 2.32 +/-
      1.24 mm for single plane images and 1.73 +/- 1.18 mm for biplane images. The
      computational efficiency of the algorithm on a desktop computer with an
      Intel((r)) Xeon((r)) CPU @3.47 GHz and an NVIDIA GeForce 690 graphic card is such
      that the time required for registering four MVA points was about 60 ms.
      CONCLUSIONS: The authors developed a rapid MVA tracking algorithm for use in the
      guidance of off-pump beating heart transapical mitral valve repair. This approach
      uses 2D biplane TEE images and was tested on a dynamic heart phantom and
      interventional porcine image data. Results regarding the accuracy and efficiency
      of the authors' MVA tracking algorithm are promising, and fulfill the
      requirements for surgical navigation.

PMID- 25563286
TI  - Robust primary modulation-based scatter estimation for cone-beam CT.
AB  - PURPOSE: Scattered radiation is one of the major problems facing image quality in
      flat detector cone-beam computed tomography (CBCT). Previously, a new scatter
      estimation and correction method using primary beam modulation has been proposed.
      The original image processing technique used a frequency-domain-based analysis,
      which proved to be sensitive to the accuracy of the modulator pattern both
      spatially and in amplitude as well as to the frequency of the modulation pattern.
      In addition, it cannot account for penumbra effects that occur, for example, due
      to the finite focal spot size and the scatter estimate can be degraded by high
      frequency components of the primary image. METHODS: In this paper, the authors
      present a new way to estimate the scatter using primary modulation. It is less
      sensitive to modulator nonidealities and most importantly can handle arbitrary
      modulator shapes and changes in modulator attenuation. The main idea is that the
      scatter estimation can be expressed as an optimization problem, which yields a
      separation of the scatter and the primary image. The method is evaluated using
      simulated and experimental CBCT data. The scattering properties of the modulator
      itself are analyzed using a Monte Carlo simulation. RESULTS: All reconstructions
      show strong improvements of image quality. To quantify the results, all images
      are compared to reference images (ideal simulations and collimated scans).
      CONCLUSIONS: The proposed modulator-based scatter reduction algorithm may open
      the field of flat detector-based imaging to become a quantitative modality. This
      may have significant impact on C-arm imaging and on image-guided radiation
      therapy.

PMID- 25563287
TI  - Latent uncertainties of the precalculated track Monte Carlo method.
AB  - PURPOSE: While significant progress has been made in speeding up Monte Carlo (MC)
      dose calculation methods, they remain too time-consuming for the purpose of
      inverse planning. To achieve clinically usable calculation speeds, a
      precalculated Monte Carlo (PMC) algorithm for proton and electron transport was
      developed to run on graphics processing units (GPUs). The algorithm utilizes
      pregenerated particle track data from conventional MC codes for different
      materials such as water, bone, and lung to produce dose distributions in
      voxelized phantoms. While PMC methods have been described in the past, an
      explicit quantification of the latent uncertainty arising from the limited number
      of unique tracks in the pregenerated track bank is missing from the paper. With a
      proper uncertainty analysis, an optimal number of tracks in the pregenerated
      track bank can be selected for a desired dose calculation uncertainty. METHODS:
      Particle tracks were pregenerated for electrons and protons using EGSnrc and
      geant4 and saved in a database. The PMC algorithm for track selection, rotation,
      and transport was implemented on the Compute Unified Device Architecture (cuda)
      4.0 programming framework. PMC dose distributions were calculated in a variety of
      media and compared to benchmark dose distributions simulated from the
      corresponding general-purpose MC codes in the same conditions. A latent
      uncertainty metric was defined and analysis was performed by varying the
      pregenerated track bank size and the number of simulated primary particle
      histories and comparing dose values to a "ground truth" benchmark dose
      distribution calculated to 0.04% average uncertainty in voxels with dose greater
      than 20% of Dmax. Efficiency metrics were calculated against benchmark MC codes
      on a single CPU core with no variance reduction. RESULTS: Dose distributions
      generated using PMC and benchmark MC codes were compared and found to be within
      2% of each other in voxels with dose values greater than 20% of the maximum dose.
      In proton calculations, a small (<= 1 mm) distance-to-agreement error was
      observed at the Bragg peak. Latent uncertainty was characterized for electrons
      and found to follow a Poisson distribution with the number of unique tracks per
      energy. A track bank of 12 energies and 60000 unique tracks per pregenerated
      energy in water had a size of 2.4 GB and achieved a latent uncertainty of
      approximately 1% at an optimal efficiency gain over DOSXYZnrc. Larger track banks
      produced a lower latent uncertainty at the cost of increased memory consumption.
      Using an NVIDIA GTX 590, efficiency analysis showed a 807 * efficiency increase
      over DOSXYZnrc for 16 MeV electrons in water and 508 * for 16 MeV electrons in
      bone. CONCLUSIONS: The PMC method can calculate dose distributions for electrons
      and protons to a statistical uncertainty of 1% with a large efficiency gain over
      conventional MC codes. Before performing clinical dose calculations, models to
      calculate dose contributions from uncharged particles must be implemented.
      Following the successful implementation of these models, the PMC method will be
      evaluated as a candidate for inverse planning of modulated electron radiation
      therapy and scanned proton beams.

PMID- 25563288
TI  - Detective quantum efficiency of photon-counting x-ray detectors.
AB  - PURPOSE: Single-photon-counting (SPC) x-ray imaging has the potential to improve
      image quality and enable novel energy-dependent imaging methods. Similar to
      conventional detectors, optimizing image SPC quality will require systems that
      produce the highest possible detective quantum efficiency (DQE). This paper
      builds on the cascaded-systems analysis (CSA) framework to develop a
      comprehensive description of the DQE of SPC detectors that implement adaptive
      binning. METHODS: The DQE of SPC systems can be described using the CSA approach
      by propagating the probability density function (PDF) of the number of image
      forming quanta through simple quantum processes. New relationships are developed
      to describe PDF transfer through serial and parallel cascades to accommodate
      scatter reabsorption. Results are applied to hypothetical silicon and selenium
      based flat-panel SPC detectors including the effects of reabsorption of
      characteristic/scatter photons from photoelectric and Compton interactions,
      stochastic conversion of x-ray energy to secondary quanta, depth-dependent charge
      collection, and electronic noise. Results are compared with a Monte Carlo study.
      RESULTS: Depth-dependent collection efficiency can result in substantial
      broadening of photopeaks that in turn may result in reduced DQE at lower x-ray
      energies (20-45 keV). Double-counting interaction events caused by reabsorption
      of characteristic/scatter photons may result in falsely inflated image signal-to
      noise ratio and potential overestimation of the DQE. CONCLUSIONS: The CSA
      approach is extended to describe signal and noise propagation through
      photoelectric and Compton interactions in SPC detectors, including the effects of
      escape and reabsorption of emission/scatter photons. High-performance SPC systems
      can be achieved but only for certain combinations of secondary conversion gain,
      depth-dependent collection efficiency, electronic noise, and reabsorption
      characteristics.

PMID- 25563289
TI  - Performance characterization of high quantum efficiency metal package
      photomultiplier tubes for time-of-flight and high-resolution PET applications.
AB  - PURPOSE: Metal package photomultiplier tubes (PMTs) with a metal channel dynode
      structure have several advanced features for devising such time-of-flight (TOF)
      and high spatial resolution positron emission tomography (PET) detectors, thanks
      to their high packing density, large effective area ratio, fast time response,
      and position encoding capability. Here, we report on an investigation of new
      metal package PMTs with high quantum efficiency (QE) for high-resolution PET and
      TOF PET detector modules. METHODS: The latest metal package PMT, the Hamamatsu
      R11265 series, is served with two kinds of photocathodes that have higher quantum
      efficiency than normal bialkali (typical QE ~ 25%), super bialkali (SBA; QE ~
      35%), and ultra bialkali (UBA; QE ~ 43%). In this study, the authors evaluated
      the performance of the new PMTs with SBA and UBA photocathodes as a PET detector
      by coupling various crystal arrays. They also investigated the performance
      improvements of high QE, focusing in particular on a block detector coupled with
      a lutetium-based scintillator. A single 4 * 4 * 10 mm(3) LYSO, a 7 * 7 array of 3
      * 3 * 20 mm(3) LGSO, a 9 * 9 array of 1.2 * 1.2 * 10 mm(3) LYSO, and a 6 * 6
      array of 1.5 * 1.5 * 7 mm(3) LuYAP were used for evaluation. All coincidence data
      were acquired with a DRS4 based fast digitizer. RESULTS: This new PMT shows
      promising crystal positioning accuracy, energy and time discrimination
      performance for TOF, and high-resolution PET applications. The authors also found
      that a metal channel PMT with SBA was enough for both TOF and high-resolution
      application, although UBA gave a minor improvement to time resolution. However,
      significant performance improvement was observed in relative low light output
      crystals (LuYAP) coupled with UBA. CONCLUSIONS: The results of this study will be
      of value as a useful reference to select PMTs for high-performance PET detectors.

PMID- 25563290
TI  - Clinical apparatus for the reduction of dose area product for patients undergoing
      x-ray catheterization.
AB  - PURPOSE: The authors describe a design for prepatient region of interest
      attenuators (ROIAs) to reduce dose area product (DAP) for clinical use. The
      authors describe a model to predict DAP values from x-ray technique parameters
      recorded during a clinical procedure for image sequences obtained in the presence
      or absence of ROIAs. The model was developed primarily to determine what the DAP
      to a patient undergoing cardiac catheterization with a ROIA would have been if no
      ROIA had been used allowing a determination of DAP reduction. METHODS: Copper
      ROIAs with thicknesses that vary gradually so as not to cause significant image
      artifacts were constructed. X-ray image sequences were acquired on a clinical
      catheterization system with and without ROIAs with varying x-ray technique
      parameters. DAP values were measured for all said exposures using an ionization
      chamber and compared to a model the authors developed. RESULTS: The model can
      predict DAP values within 3.5% on average with or without ROIAs when compared to
      ionization chamber measurements. CONCLUSIONS: The proposed experimental design is
      adequate for measuring DAP reductions on the order of 1.5-3.5 that are expected
      when introducing a ROIA during patient catheterization imaging.

PMID- 25563293
TI  - Proline-Rich Peptides: Multifunctional Bioactive Molecules As New Potential
      Therapeutic Drugs.
AB  - Proline-rich peptides (PRPs) include a large and heterogeneous group of small
      medium sized peptides characterized by the presence of proline residues often
      constituting peculiar sequences. This feature confers them a typical structure
      that determines the various biological functions endowed by these molecules. In
      particular the left-handed-polyproline-II helix is essential for the expression
      of the antimicrobial, immunomodulatory, antioxidant properties and to finely
      modulate protein-protein interactions, thus playing crucial roles in many cell
      signal transduction pathways. These peptides are widely diffuse in the animal
      kingdom and in humans, where they are present in many tissues and biological
      fluids. This review highlights the most relevant biological properties of these
      peptides, focusing on the potential therapeutic role that the PRPs may play as a
      promising source of new peptide-based novel drugs.

PMID- 25563291
TI  - Twenty Years of Alcohol Septal Ablation in Hypertrophic Obstructive
      Cardiomyopathy.
AB  - Hypertrophic obstructive cardiomyopathy is the most common genetic cardiac
      disease and is generally characterised by asymmetric septal hypertrophy and
      intraventricular obstruction. Patients with severe obstruction and significant
      symptoms that persist despite optimal medical treatment are candidates for an
      invasive septal reduction therapy. Twenty years after its introduction,
      percutaneous transluminal alcohol septal ablation has been increasingly preferred
      for septal reduction in patients with drug refractory hypertrophic obstructive
      cardiomyopathy. Myocardial contrast echocardiography and injection of reduced
      alcohol volumes have increased safety, while efficacy is comparable to the
      surgical alternative, septal myectomy, which has for decades been regarded as the
      'gold standard' treatment. Data on medium- and long-term survival show improved
      prognosis with survival being similar to the general population. Current
      guidelines have supported its use by experienced operators in centres specialised
      in the treatment of patients with hypertrophic obstructive cardiomyopathy.

PMID- 25563294
TI  - Alternative NHEJ Pathway Components Are Therapeutic Targets in High-Risk
      Neuroblastoma.
AB  - In neuroblastoma, MYCN genomic amplification and segmental chromosomal
      alterations including 1p or 11q loss of heterozygocity and/or 17q gain are
      associated with progression and poor clinical outcome. Segmental alterations are
      the strongest predictor of relapse and result from unbalanced translocations
      attributable to erroneous repair of chromosomal breaks. Although sequence
      analysis of affected genomic regions suggests that these errors arise by
      nonhomologous end-joining (NHEJ) of DNA double-strand breaks (DSB), abnormalities
      in NHEJ have not been implicated in neuroblastoma pathogenesis. On this basis,
      the hypothesis that an error-prone mechanism of NHEJ is critical for
      neuroblastoma cell survival was tested. Plasmid-based DSB repair assays
      demonstrated efficient NHEJ activity in human neuroblastoma cells with repair
      products that were error-prone relative to nontransformed cells. Neuroblastoma
      cells derived from tumorigenic neuroblastic phenotypes had differential DNA
      repair protein expression patterns compared with nontumorigenic cells.
      Tumorigenic neuroblastoma cells were deficient in DNA ligase IV (Lig4) and
      Artemis (DCLRE1C), mediators of canonical NHEJ. Conversely, enzymes required for
      an error-prone alternative NHEJ pathway (alt-NHEJ), DNA Ligase IIIalpha (Lig3),
      DNA Ligase I (Lig1), and PARP1 protein were upregulated. Inhibition of Lig3 and
      Lig1 led to DSB accumulation and cell death, linking alt-NHEJ to cell survival in
      neuroblastoma. Neuroblastoma cells demonstrated sensitivity to PARP1 inhibition
      (PARPi) that paralleled PARP1 expression. In a dataset of human neuroblastoma
      patient tumors, overexpression of genes encoding alt-NHEJ proteins associated
      with poor survival. IMPLICATIONS: These findings provide an insight into DNA
      repair fidelity in neuroblastoma and identify components of the alt-NHEJ pathway
      as promising therapeutic targets.

PMID- 25563295
TI  - Mental resilience training modulates stress physiology of active duty marines
      preparing for deployment.

PMID- 25563292
TI  - A review of the relationships between endogenous sex steroids and incident
      ischemic stroke and coronary heart disease events.
AB  - For decades, it has been recognized that men have a higher age-adjusted risk of
      ischemic cardiovascular (CVD) events compared to women, thus generating
      hypotheses that sex steroids contribute to CVD risk. Potential mechanisms include
      genomic and non-genomic effects of sex steroids as well as mediation through
      classic CVD risk factors and obesity. However, results from randomized studies
      suggest that sex steroid supplementation in men and women do not result in
      improved CVD outcomes and may increase CVD risk. In contrast, prospective
      observations from endogenous sex steroid studies, i.e. among participants not
      using sex steroids, have suggested the opposite relationship. We reviewed the
      findings of prospective observational studies in men (17 studies) and women (8
      studies) that examined endogenous sex steroids and CVD risk. These studies
      suggested a lack of association or that lower levels of testosterone or
      dihydrotestosterone are associated with higher CVD risk in both men and women.
      Higher, rather than lower, estradiol levels were associated with higher CVD risk
      in women. There were several significant gaps in the literature. First, it is
      unclear whether more sensitive measures of sex steroid levels might detect
      significant differences. Second, there are few prospective studies in women.
      Similarly, no studies report outcomes for high-risk groups such as African
      Americans and Hispanics. Finally, few studies report upon ischemic coronary
      disease as opposed to ischemic stroke separately, although relationships between
      sex steroids and CVD may vary by vascular bed. Future investigations need to
      examine high risk groups and to distinguish between subtypes of CVD. 

PMID- 25563296
TI  - Utilization of the ex vivo LLNA: BrdU-ELISA to distinguish the sensitizers from
      irritants in respect of 3 end points-lymphocyte proliferation, ear swelling, and
      cytokine profiles.
AB  - Dermal exposure to chemicals may result in allergic or irritant contact
      dermatitis. In this study, we performed ex vivo local lymph node assay:
      bromodeoxyuridine-enzyme-linked immunosorbent assay (LLNA: BrdU-ELISA) to compare
      the differences between irritation and sensitization potency of some chemicals in
      terms of the 3 end points: lymphocyte proliferation, cytokine profiles
      (interleukin 2 [IL-2], interferon-gamma (IFN-gamma), IL-4, IL-5, IL-1, and tumor
      necrosis factor alpha [TNF-alpha]), and ear swelling. Different concentrations of
      the following well-known sensitizers and irritant chemicals were applied to mice:
      dinitrochlorobenzene, eugenol, isoeugenol, sodium lauryl sulfate (SLS), and
      croton oil. According to the lymph node results; the auricular lymph node weights
      and lymph node cell counts increased after application of both sensitizers and
      irritants in high concentrations. On the other hand, according to lymph node cell
      proliferation results, there was a 3-fold increase in proliferation of lymph node
      cells (stimulation index) for sensitizer chemicals and SLS in the applied
      concentrations; however, there was not a 3-fold increase for croton oil and
      negative control. The SLS gave a false-positive response. Cytokine analysis
      demonstrated that 4 cytokines including IL-2, IFN-gamma, IL-4, and IL-5 were
      released in lymph node cell cultures, with a clear dose trend for sensitizers
      whereas only TNF-alpha was released in response to irritants. Taken together, our
      results suggest that the ex vivo LLNA: BrdU-ELISA method can be useful for
      discriminating irritants and allergens. 

PMID- 25563297
TI  - 'I don't get this climate stuff!' Making sense of climate change among the
      corporate middle class in Lagos.
AB  - Public engagement continues to be central to wider efforts to address climate
      change. This study contributes to public engagement debates by investigating
      engagement with climate change among an often overlooked group, the corporate
      middle class in Africa's second largest megacity, Lagos. Combining survey and
      interviews, I focus analysis on three aspects: awareness, knowledge and concern;
      role of scientific and social frames in shaping general attitude; and spatial
      attribution of causes and consequences. The study reveals a universal awareness
      and high concern about climate change among the respondents, although
      understanding and perceptions of climate change are significantly socially
      framed. Social situatedness, more than scientific facts, is the most important
      definer of overall engagement with climate change. This study thus underscores a
      nuanced constructionist stance, showing how corporate professionals' 'ways of
      knowing' climate change is underpinned by a certain co-production between
      scientific and socio-experiential frames. I highlight implications for research
      and public engagement with climate change. 

PMID- 25563299
TI  - Can motivational interviewing in emergency care reduce alcohol consumption in
      young people? A systematic review and meta-analysis.
AB  - AIMS: We investigate the effect of motivational interviewing (MI), delivered in a
      brief intervention during an emergency care contact, on the alcohol consumption
      of young people who screen positively for present or previous risky alcohol
      consumption. METHODS: MEDLINE, CINAHL, EMBASE, PsycARTICLES, PsycINFO, PSYNDEX
      and Scopus were searched for randomized controlled trials with adolescents or
      young adults that compared MI in an emergency care setting to control conditions
      and measured drinking outcomes. RESULTS: Six trials with 1433 participants, aged
      13-25 years, were included in the systematic review and meta-analysis. MI was
      never less efficacious than a control intervention. Two trials found
      significantly more reduction in one or more measures of alcohol consumption in
      the MI intervention group. One trial indicated that MI may be used most
      effectively in young people with high-volume alcohol consumption. Separate random
      effects meta-analyses were performed based on the highest impact that MI added on
      reducing the drinking frequency and the drinking quantity at any point in time
      during the different study periods. Their results were expressed as standardized
      mean differences (SMDs). The frequency of drinking alcohol decreased
      significantly more after MI than after control interventions (SMD <= -0.17, P <=
      0.03). In addition, MI reduced the drinking quantity further than control
      interventions in a meta-analysis of the subset of trials that were implemented in
      the USA (SMD = -0.12, P = 0.04). Meta-analyses of the smallest mean differences
      between MI and control groups detected no differences in alcohol use (SMD <=
      0.02, P >= 0.38). CONCLUSION: MI appears at least as effective and may possibly
      be more effective than other brief interventions in emergency care to reduce
      alcohol consumption in young people.

PMID- 25563298
TI  - Solution NMR and calorimetric analysis of Rem2 binding to the Ca2+ channel beta4
      subunit: a low affinity interaction is required for inhibition of Cav2.1 Ca2+
      currents.
AB  - Rem, Rad, Kir/Gem (RGK) proteins, including Rem2, mediate profound inhibition of
      high-voltage activated Ca(2+) channels containing intracellular regulatory beta
      subunits. All RGK proteins bind to voltage-gated Ca(2+) channel beta subunit
      (Cavbeta) subunits in vitro, but the necessity of the interaction for current
      inhibition remains controversial. This study applies NMR and calorimetric
      techniques to map the binding site for Rem2 on human Cavbeta4a and measure its
      binding affinity. Our experiments revealed 2 binding surfaces on the beta4
      guanylate kinase domain contributing to a 156 +/- 18 uM Kd interaction: a
      hydrophobic pocket lined by 4 critical residues (L173, N261, H262, and V303),
      mutation of any of which completely disrupted binding, and a nearby surface
      containing 3 residues (D206, L209, and D258) that when individually mutated
      decreased affinity. Voltage-gated Ca(2+) channel alpha1A subunit (Cav2.1) Ca(2+)
      currents were completely inhibited by Rem2 when co-expressed with wild-type
      Cavbeta4a, but were unaffected by Rem2 when coexpressed with a Cavbeta4a site 1
      (L173A/V303A) or site 2 (D258A) mutant. These results provide direct evidence for
      a low-affinity Rem2/Cavbeta4 interaction and show definitively that the
      interaction is required for Cav2.1 inhibition.

PMID- 25563300
TI  - Signaling pathway STAT1 is strongly activated by IFN-beta in the pathogenesis of
      osteoporosis.
AB  - BACKGROUND: Despite extensive research, the underlying pathological mechanisms of
      osteoporosis are not completely understood. Recent studies have indicated a
      distinct role for the IFN-beta/STAT1 pathway in bone metabolism. An inhibitory
      effect of IFN-beta on osteoclastogenesis has been detected and STAT1/2 has been
      shown to influence osteoblastic bone metabolism. So far, no data concerning the
      IFN-beta/STAT1 pathways in osteoblasts and osteoclasts from osteoporotic and non
      osteoporotic patients are available. The aim of the study was to analyze these
      pathways in both cell types. METHODS: Osteoblasts were isolated from the femoral
      heads of 12 osteoporotic and 11 non-osteoporotic patients and monocytes were
      differentiated into osteoclasts. After the differentiation period, cells were
      stimulated once with 20 and 100 ng/mL IFN-beta for 4 days. Viability, activity,
      bone metabolism-related genes, and the proteins Fra1, SOCS1, STAT1, p-STAT1, and
      TRAF6 were analyzed. RESULTS: Viability, activity, and gene expressions were not
      affected by stimulating the osteoblasts. However, in osteoporotic osteoclasts,
      which display a significantly higher basal osteoclastic activity, the stimulation
      with IFN-beta lead to significant inhibition. Further, an increased STAT1
      activation was detected in both cell types with no significant differences
      between the groups. Regarding the phosphorylation of STAT1, no significant
      influence was detected in osteoblasts but the IFN-beta stimulation led to a
      significant increase of p-STAT1 in osteoclasts of both groups. CONCLUSIONS: IFN
      beta is a principal mediator in the pathogenesis of osteoporosis by inhibiting
      osteoclasts and inducing and activating STAT1. Our results also confirm this in
      cells from osteoporotic and non-osteoporotic patients. Strong inhibitory effects
      on the osteoclastogenesis of osteoporotic osteoclasts were detectable.
      Nevertheless, osteoblast activity was not negatively affected by IFN-beta
      stimulation. These results may contribute to a better understanding of the
      underlying pathological signaling pathways of osteoporosis.

PMID- 25563301
TI  - Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing
      technology and application.
AB  - BACKGROUND: Long-range chromatin interactions play an important role in
      transcription regulation. Chromatin Interaction Analysis with Paired-End-Tag
      sequencing (ChIA-PET) is an emerging technology that has unique advantages in
      chromatin interaction analysis, and thus provides insight into the study of
      transcription regulation. RESULTS: This article introduces the experimental
      protocol and data analysis process of ChIA-PET, as well as discusses some
      applications using this technology. It also unveils the direction of future
      studies based on this technology. CONCLUSIONS: Overall we show that ChIA-PET is
      the cornerstone to explore the three-dimensional (3D) chromatin structure, and
      certainly will lead the forthcoming wave of 3D genomics studies.

PMID- 25563302
TI  - Evidence-based treatment for adult women with child abuse-related Complex PTSD: a
      quantitative review.
AB  - INTRODUCTION: Effective first-line treatments for posttraumatic stress disorder
      (PTSD) are well established, but their generalizability to child abuse (CA)
      related Complex PTSD is largely unknown. METHOD: A quantitative review of the
      literature was performed, identifying seven studies, with treatments specifically
      targeting CA-related PTSD or Complex PTSD, which were meta-analyzed, including
      variables such as effect size, drop-out, recovery, and improvement rates.
      RESULTS: Only six studies with one or more cognitive behavior therapy (CBT)
      treatment conditions and one with a present centered therapy condition could be
      meta-analyzed. RESULTS indicate that CA-related PTSD patients profit with large
      effect sizes and modest recovery and improvement rates. Treatments which include
      exposure showed greater effect sizes especially in completers' analyses, although
      no differential results were found in recovery and improvement rates. However,
      results in the subgroup of CA-related Complex PTSD studies were least favorable.
      Within the Complex PTSD subgroup, no superior effect size was found for exposure,
      and affect management resulted in more favorable recovery and improvement rates
      and less drop-out, as compared to exposure, especially in intention-to-treat
      analyses. CONCLUSION: Limited evidence suggests that predominantly CBT treatments
      are effective, but do not suffice to achieve satisfactory end states, especially
      in Complex PTSD populations. Moreover, we propose that future research should
      focus on direct comparisons between types of treatment for Complex PTSD patients,
      thereby increasing generalizability of results.

PMID- 25563303
TI  - Dynamics of miRNA driven feed-forward loop depends upon miRNA action mechanisms.
AB  - BACKGROUND: We perform the theoretical analysis of a gene network sub-system,
      composed of a feed-forward loop, in which the upstream transcription factor
      regulates the target gene via two parallel pathways: directly, and via
      interaction with miRNA. RESULTS: As the molecular mechanisms of miRNA action are
      not clear so far, we elaborate three mathematical models, in which miRNA either
      represses translation of its target or promotes target mRNA degradation, or is
      not re-used, but degrades along with target mRNA. We examine the feed-forward
      loop dynamics quantitatively at the whole time interval of cell cycle. We
      rigorously proof the uniqueness of solutions to the models and obtain the exact
      solutions in one of them analytically. CONCLUSIONS: We have shown that different
      mechanisms of miRNA action lead to a variety of types of dynamical behavior of
      feed-forward loops. In particular, we found that the ability of feed-forward loop
      to dampen fluctuations introduced by transcription factor is the model and
      parameter dependent feature. We also discuss how our results could help a
      biologist to infer the mechanism of miRNA action.

PMID- 25563304
TI  - Socio-economic characteristics, living conditions and diet quality are associated
      with food insecurity in France.
AB  - OBJECTIVE: To assess the prevalence of household food insecurity (FI) in France
      and to describe its associations with socio-economic factors, health behaviours,
      diet quality and cost (estimated using mean food prices). DESIGN: Cross-sectional
      nationally representative survey. FI was assessed using an adapted version of the
      US Department of Agriculture's Food Insufficiency Indicator; dietary intake was
      assessed using a 7 d open-ended food record; and individual demographic, socio
      economic and behavioural variables were assessed using self-administered
      questionnaires and interviews. Individuals experiencing FI were compared with
      food-secure individuals, the latter being divided into four categories according
      to quartiles of their income per consumption unit (FS1 to FS4). Differences among
      categories were analysed using chi2 tests, ANOVA and tests for trend. SETTING:
      Individual and National Dietary Survey (INCA2), 2006-2007. SUBJECTS: Adults aged
      18-79 years (n 2624). RESULTS: Individuals experiencing FI represented 12.2% of
      the population. They were on average younger, more frequently women and single
      parents with children compared with those in the other four categories. Their
      mean income per consumption unit was higher than that in the FS1 category, but
      they reported poorer material and housing conditions. The prevalence of smoking
      and the mean daily time spent watching television were also higher in the FI
      category. No significant difference among categories was found for energy intake,
      but mean intakes of fruits, vegetables and fish were lower, and diet quality was
      slightly but significantly poorer in the FI category. Daily diet cost was also
      lower in the FI category. CONCLUSIONS: France is not spared by FI. FI should be
      routinely monitored at the national level and research should be promoted to
      identify effective strategies to reduce nutrition inequalities in France.

PMID- 25563305
TI  - A multicentre prospective evaluation of the impact of renal insufficiency on in
      hospital and long-term mortality of patients with acute ST-elevation myocardial
      infarction.
AB  - BACKGROUND: Numerous previous studies have shown that renal insufficiency (RI) in
      patients with acute coronary syndrome is associated with poor cardiovascular
      outcomes. These studies do not well address the impact of RI on the long-term
      outcome of patients with acute ST-elevation myocardial infarction (STEMI) in
      China. The aim of this study was to investigate the association of admission RI
      and inhospital and long-term mortality of patients with acute STEMI. METHODS:
      This was a multicenter, observational, prospective-cohort study. 718 consecutive
      patients were admitted to 19 hospitals in Beijing within 24 hours of onset of
      STEMI, between January 1,2006 and December 31,2006. Estimation of glomerular
      filtration rate (eGFR) was calculated using the modified abbreviated modification
      of diet in renal disease equation-based on the Chinese chronic kidney disease
      patients. The patients were categorized according to eGFR, as normal renal
      dysfunction (eGFR >= 90 ml.min -1.1.73 m -2 ), mild RI (60 ml.min -1.1.73 m -2 <=
      eGFR < 90 ml.min -1.1.73 m -2 ) and moderate or severe RI (eGFR < 60 ml.min 
      1.1.73 m -2 ). The association between RI and inhospital and 6-year mortality of
      was evaluated. RESULTS: Seven hundred and eighteen patients with STEMI were
      evaluated. There were 551 men and 167 women with a mean age of 61.0 +/- 13.0
      years. Two hundred and eighty patients (39.0%) had RI, in which 61 patients
      (8.5%) reached the level of moderate or severe RI. Patients with RI were more
      often female, elderly, hypertensive, and more patients had heart failure and
      stroke with higher killip class. Patients with RI were less likely to present
      with chest pain. The inhospital mortality (1.4% vs. 5.9% vs. 22.9%, P < 0.001), 6
      year all-cause mortality (9.5% vs. 19.8 vs. 45.2%, P < 0.001) and 6-year cardiac
      mortality (2.9% vs. 12.2% vs. 23.8%, P < 0.001) were markedly increased in
      patients with RI. After adjusting for other confounding factors, classification
      of admission renal function was an independent predictor of inhospital mortality
      (Odd ratio, 1.966; 95% confidence interval [CI], 1.002-3.070, P = 0.019), 6-year
      all-cause mortality (relative risk [RR] = 1.501, 95% CI: 1.018-4.373, P = 0.039)
      and 6-year cardiac mortality (RR = 1.663, 95% CI: 1.122-4.617, P = 0.042).
      CONCLUSIONS: RI is very common in STEMI patients. RI evaluated by eGFR is an
      important independent predictor of short-term and long-term outcome in patients
      with acute STEMI.

PMID- 25563306
TI  - The survey of birth defects rate based on birth registration system.
AB  - BACKGROUND: To investigate the surveillance trend of birth defects, incidence,
      distribution, occurrence regularity, and their relevant factors in Xi'an City in
      the last 10 years for proposing control measures. METHODS: The birth defects
      monitoring data of infants during perinatal period (28 weeks of gestation to 7
      days after birth) were collected from obstetrics departments of all hospitals
      during 2003-2012. Microsoft Excel 2003 was used for data input, and Statistical
      Package for the Social Sciences version 16.0 (International Business Machines
      Corporation, New York, NY, USA) was used for descriptive analysis. chi2 test,
      Spearman correlation and linear-by-linear association trend test were used for
      statistical analyses. RESULTS: The birth defect rate declined from 9.18% in 2003
      to 7.00% in 2012 (chi2 = 45.001, P < 0.01) with a mean value of 7.85%, which is
      below the Chinese national average level (chi2 = 20.451, P < 0.01). The order of
      five most common birth defects has changed. The incidence of congenital heart
      disease (CHD) increased with time, particularly after 2012, it became the most
      frequent type (r s = 0.808, P < 0.001). Till then, the number of neural tube
      defects (NTDs) declined significantly (chi2 = 76.254, P < 0.01). The average
      birth defects rate of 8.11% in rural areas was higher than that in urban areas
      (7.56%, chi2 = 7.919, P < 0.01) and much higher in males (8.28%) than that in
      females (7.18%, chi2 = 32.397, P < 0.01). Maternal age older than 35 years (chi2
      = 35.298, P < 0.01) is the most dangerous age bracket of birth defects than
      maternal age younger than 20 years (chi2 = 7.128, P < 0.01). CONCLUSIONS: A
      downward trend of birth defects was observed in Xi'an City from 2003 to 2012.
      NTDs significantly decreased after large-scale supplemental folic acid
      intervention, while the incidence rate of CHD significantly increased.

PMID- 25563308
TI  - Granulocyte colony-stimulating factor-primed bone marrow: an excellent stem-cell
      source for transplantation in acute myelocytic leukemia and chronic myelocytic
      leukemia.
AB  - BACKGROUND: Steady-state bone marrow (SS-BM) and granulocyte colony-stimulating
      growth factor-primed BM/peripheral blood stem-cell (G-BM/G-PBSC) are the main
      stem-cell sources used in allogeneic hematopoietic stem-cell transplantation.
      Here, we evaluated the treatment effects of SS-BM and G-BM/G-PBSC in human
      leucocyte antigen (HLA)-identical sibling transplantation. METHODS: A total of
      226 patients (acute myelogenous leukemia-complete remission 1, chronic
      myelogenous leukemia-chronic phase 1) received SS-BM, G-BM, or G-PBSC from an HLA
      identical sibling. Clinical outcomes (graft-versus-host disease [GVHD], overall
      survival, transplant-related mortality [TRM], and leukemia-free survival [LFS])
      were analyzed. RESULTS: When compared to SS-BM, G-BM gave faster recovery time to
      neutrophil or platelet (P < 0.05). Incidence of grade III-IV acute GVHD and
      extensive chronic GVHD (cGVHD) was lower than seen with SS-BM (P < 0.05) and
      similar to G-PBSC. Although the incidence of cGVHD in the G-BM group was similar
      to SS-BM, both were lower than G-PBSC (P < 0.05). G-BM and G-PBSC exhibited
      similar survival, LFS, and TRM, but were significantly different from SS-BM (P <
      0.05). There were no significant differences in leukemia relapse rates among the
      groups (P > 0.05). CONCLUSIONS: G-CSF-primed bone marrow shared the advantages of
      G-PBSC and SS-BM. We conclude that G-BM is an excellent stem-cell source that may
      be preferable to G-PBSC or SS-BM in patients receiving HLA-identical sibling
      hematopoietic stem-cell transplantation.

PMID- 25563307
TI  - Comparison of congenital coronary artery anomalies between Uyghur and Han: a
      multi-slice computed tomography study in Xinjiang, China.
AB  - BACKGROUND: The incidence of congenital coronary artery anomalies (CCAAs) is
      different between ethnic groups, but there is no report about Uyghur CCAAs
      because of the limitation of inspection methods. This study determined the
      prevalence of Uyghur CCAAs and analysis the difference of CCAAs between Uyghur
      and Han ethnic groups by the method of multi-slice computed tomography coronary
      angiography (MSCTCA). METHODS: Seven thousand four hundred and sixty-nine MSCTCA
      were analyzed for the CCAAs retroactively, 1934 were Uyghur patients while 4746
      were Han patients. All the coronary artery images dates obtained by MSCTCA were
      evaluated for the CCAAs by two doctors. RESULTS: Nineteen kinds of CCAAs were
      found: (1) The overall incidence of CCAAs was 2.72% (203/7469) among all
      patients, 2.34% (111/4746) among Han patients whereas a significant higher 3.93%
      (76/1934) among Uyghur patients (chi2 = 12.780,P < 0.05); (2) the incidence of
      CCAAs among male patients was 2.48% (76/3069) in Han while 4.33% (56/1293) in
      Uyghur (chi2 = 10.663, P < 0.05); (3) the incidence of CCAAs on the left side was
      1.07% (51/4746) among Han patients while 2.17% (42/934) among Uyghur patients
      (chi2 = 12.047, P < 0.05); (4) among these 19 kinds of CCAAs, there were
      significant differences of the incidence of the following kinds of CCAAs between
      Uyghur and Han: Left coronary artery (LCA) high location (chi2 = 8.320, P =
      0.004), right coronary artery (RCA) originate from left coronary sinus (chi2 =
      5.450, P = 0.020), and RCA originate from left Coronary sinus + LCA high location
      (P = 0.024). CONCLUSIONS: There exists some difference in CCAAs between Uyghur
      and Han ethnic groups. The CCAAs incidence of Uyghur is higher than that of Han,
      especially in male patients and on the left side; among all kinds of CCAAs, the
      incidence of LCA high location, RCA originate from left coronary sinus, RCA
      originate from left coronary sinus + LCA high locations of Uyghur is higher than
      Han.

PMID- 25563309
TI  - Assessment of adaptive rate response provided by accelerometer, minute
      ventilation and dual sensor compared with normal sinus rhythm during exercise: a
      self-controlled study in chronotropically competent subjects.
AB  - BACKGROUND: Dual sensor (DS) for rate adaption was supposed to be more
      physiological. To evaluate its superiority, the DS (accelerometer [ACC] and
      minute ventilation [MV]) and normal sinus rate response were compared in a self
      controlled way during exercise treadmill testing. METHODS: This self-controlled
      study was performed in atrioventricular block patients with normal sinus function
      who met the indications of pacemaker implant. Twenty-one patients came to the 1
      month follow-up visit. Patients performed a treadmill test 1-month post implant
      while programmed in DDDR and sensor passive mode. For these patients, sensor
      response factors were left at default settings (ACC = 8, MV = 3) and sensor
      indicated rates (SIRs) for DS, ACC and MV sensor were retrieved from the
      pacemaker memories, along with measured sinus node (SN) rates from the beginning
      to 1-minute after the end of the treadmill test, and compared among study groups.
      Repeated measures analysis of variance and profile analysis, as well as variance
      analysis of randomized block designs, were used for statistical analysis.
      RESULTS: Fifteen patients (15/21) were determined to be chronotropically
      competent. The mean differences between DS SIRs and intrinsic sinus rates during
      treadmill testing were smaller than those for ACC and MV sensor (mean difference
      between SIR and SN rate: ACC vs. SN, MV vs. SN, DS vs. SN, respectively, 34.84,
      17.60, 16.15 beats/min), though no sensors could mimic sinus rates under the
      default settings for sensor response factor (ACC vs. SN P-adjusted < 0.001; MV
      vs. SN P-adjusted = 0.002; DS vs. SN P-adjusted = 0.005). However, both in the
      range of 1 st minute and first 3 minutes of exercise, only the DS SIR profile did
      not differ from sinus rates (P-adjusted = 0.09, 0.90, respectively). CONCLUSIONS:
      The DS under default settings provides more physiological rate response during
      physical activity than the corresponding single sensors (ACC or MV sensor).
      Further study is needed to determine if individual optimization would further
      improve adaptive performance of the DS.

PMID- 25563310
TI  - Clinical and genetic investigation of a multi-generational Chinese family
      afflicted with Von Hippel-Lindau disease.
AB  - BACKGROUND: Von Hippel-Lindau (VHL) disease is a hereditary tumor disorder caused
      by mutations or deletions of the VHL gene. Few studies have documented the
      clinical phenotype and genetic basis of the occurrence of VHL disease in China.
      This study armed to present clinical and genetic analyses of VHL within a five
      generation VHL family from Northwestern China, and summarize the VHL mutations
      and clinical characteristics of Chinese families with VHL according to previous
      studies. METHODS: An epidemiological investigation of family members was done to
      collect the general information. A retrospective study of clinical VHL cases was
      launched to collect the relative clinical data. Genetic linkage and haplotype
      analysis were used to make sure the linkage of VHL to disease in this family. The
      VHL gene screening was performed by directly analyzing DNA sequence output. At
      last, we summarized the VHL gene mutation in China by the literature review.
      RESULTS: A five-generation North-western Chinese family afflicted with VHL
      disease was traced in this research. The family consisted of 38 living family
      members, of whom nine were affected. The individuals afflicted with VHL exhibited
      multi-organ tumors that included pheochromocytomas (8), central nervous system
      hemangioblastomas (3), pancreatic endocrine tumors (2), pancreatic cysts (3),
      renal cysts (4), and paragangliomas (2). A linkage analysis resulted in a high
      maximal LOD score of 8.26 (theta = 0.0) for the marker D3S1263, which is in the
      same chromosome region as VHL. Sequence analysis resulted in the identification
      of a functional C>T transition mutation (c. 499 C>T, p.R167W) located in exon 3
      of the 167 th codon of VHL. All affected individuals shared this mutation,
      whereas the unaffected family members and an additional 100 unrelated healthy
      individuals did not. To date, 49 mutations have been associated with this disease
      in Chinese populations. The most frequent VHL mutations in China are p.S65 W,
      p.N78 S, p.R161Q and p.R167 W. CONCLUSIONS: The results supported the notion that
      the genomic sequence that corresponds to the 167 th residue of VHL is a
      mutational hotspot. Further research is needed to clarify the molecular role of
      VHL in the development of organ-specific tumors.

PMID- 25563312
TI  - Clinical efficacy of oral ganciclovir for prophylaxis and treatment of recurrent
      herpes simplex keratitis.
AB  - BACKGROUND: Herpes simplex keratitis (HSK) caused by herpes simplex virus 1 (HSV
      1), which has high recurrent rate and incidence of severe vision loss, is the
      leading cause of infectious blindness in the world. The aim was to explore the
      clinical efficacy of oral ganciclovir (GCV) in the prevention of recurrent HSK.
      METHODS: A multicenter, prospective, randomized, single-blind, and controlled
      clinical trial was conducted from April 2010 to June 2013. One hundred seventy
      three patients (173 eyes involved) who were diagnosed as recurrent HSK
      definitely, including stromal keratitis and corneal endotheliitis, were divided
      into three groups randomly: negative control (placebo) group was topically
      administered with 0.15% GCV ophthalmic gel, 4 times per day and 0.1%
      fluorometholone eye drops, 3 times per day until resolution of HSK; positive
      control acyclovir (ACV) group was topically adopted the same ophthalmic gel and
      eye drops and additionally received oral ACV 400 mg 5 times a day for 10 weeks
      and followed by 400 mg 2 times per day for 6 months; test GCV group was topically
      adopted the same treatment as negative control group and additionally received
      oral GCV 1000 mg 3 times per day for 8 weeks. The symptoms and signs were
      evaluated before and after the therapy 1 st week, 2 nd week and then followed up
      every 2 weeks until recovery. Furthermore, we followed up recurrence of HSK for
      every 3 months after recovery and then assessed the cure time, recurrent rate and
      adverse reactions. RESULTS: One hundred and seventy-three patients were followed
      up 7-48 months (mean 32.1 +/- 12.3 months), but 34 patients were failed to follow
      up. The cure time was 12.1 +/- 4.3, 11.9 +/- 4.0 weeks in negative control
      (placebo) group and positive control ACV group respectively (P = 0.991), which
      was longer than that in test GCV group (8.6 +/- 2.8 weeks) and there was a
      significant difference between test GCV group and negative control (placebo)
      group or positive control ACV group (P = 0.000). Furthermore, the recurrent rate
      was higher in negative control (placebo) group (47.3%) than that in positive
      control group ACV (26.7%) and test GCV group (17.2%), and there was a great
      significant difference among the three groups (P = 0.007), but there was no
      significant difference between positive control ACV group and test GCV group (P =
      0.358). In addition, there was no obvious adverse reaction expect neutropenia
      (only one patient in test GCV group). CONCLUSION: Short-term oral GCV could cure
      recurrent HSK and endotheliitis, shorten the course, reduce recurrent rate of HSK
      and have confirmed safety.

PMID- 25563311
TI  - Efficacy of add-on montelukast in nonasthmatic eosinophilic bronchitis: the
      additive effect on airway inflammation, cough and life quality.
AB  - BACKGROUND: The efficacy of montelukast (MONT), a cysteinyl leukotriene receptor
      antagonist, in nonasthmatic eosinophilic bronchitis (NAEB), especially its
      influence on cough associated life quality is still indefinite. We evaluated the
      efficacy of MONT combined with budesonide (BUD) as compared to BUD monotherapy in
      improving life quality, suppressing airway eosinophilia and cough remission in
      NAEB. METHODS: A prospective, open-labeled, multicenter, randomized controlled
      trial was conducted. Patients with NAEB (aged 18-75 years) were randomized to
      inhaled BUD (200 MUg, bid) or BUD plus oral MONT (10 MUg, qn) for 4 weeks.
      Leicester cough questionnaire (LCQ) life quality scores, cough visual analog
      scale (CVAS) scores, eosinophil differential ratio (Eos), and eosinophil cationic
      protein (ECP) in induced sputum were monitored and compared. RESULTS: The control
      and MONT groups contained 33 and 32 patients, respectively, with similar baseline
      characteristics. Significant with-in group improvement in CVAS, LCQ scores, Eos,
      and ECP was observed in both groups during treatment. After 2-week treatment, add
      on treatment of MONT was significantly more effective than BUD monotherapy for
      CVAS decrease and LCQ scores improvement (both P < 0.05). Similar results were
      seen at 4-week assessment (both P < 0.05). 4-week add-on therapy of MONT also
      resulted in a higher percentage of patients with normal sputum Eos (<2.5%) and
      greater decrease of ECP (both P < 0.05). CONCLUSIONS: MONT combined with BUD was
      demonstrated cooperative effects in improvement of life quality, suppression of
      eosinophilic inflammation, and cough remission in patients with NAEB.

PMID- 25563313
TI  - Radiological characteristics and anatomical risk factors in the evaluation of
      hallux valgus in chinese adults.
AB  - BACKGROUND: There are no unified theories as to the anatomical changes that occur
      with hallux valgus, we investigated the radiological characteristics and
      anatomical risk factors for hallux valgus deformity in Chinese adults. METHODS:
      We reviewed 141 patients with hallux valgus (206 feet; 15 males, 126 females;
      mean age, 58.5 years). These patients attended Peking University People's
      Hospital from April 2008 to March 2014. All feet had intact radiological data,
      obtained using the Centricity RIS/PACS system. We measured hallux valgus angle
      (HVA), 1-2 intermetatarsal angle (IMA), proximal articular set angle (PASA),
      distal articular set angle, hallux interphalangeal angle, metatarsocuneiform
      angle, size of the medial eminence of the distal first metatarsal, tibial
      sesamoid position, and joint congruity of the first metatarsophalangeal joint
      (MTPJ). RESULTS: We found positive correlations between the HVA and IMA (r =
      0.279, P < 0.01) and HVA and PASA (r = 0.358, P < 0.01), but not for IMA and PASA
      (P > 0.05). Feet were divided into three groups based on HVA severity. IMA (P <
      0.05) and PASA (P < 0.05) in the mild group were significantly lower than that in
      the moderate and severe groups, with no significant difference determined for IMA
      or PASA between the moderate and severe groups (P > 0.05). Feet were then grouped
      based on the shape of the first metatarsal head. Using this grouping, HVA was
      significant higher in the rounded shape (19.92 degrees ) than in a flat shape
      (17.66 degrees ). The size of the medial eminence of the distal first metatarsal
      was positively correlated with HVA (r = 0.185, P < 0.01). The medial eminence in
      the moderate and severe groups was significantly larger than that in the mild
      group; moderate and severe groups were not significantly different. CONCLUSIONS:
      PASA enlargement is an adaptive change during early hallux valgus formation, and
      decompensation leads to subdislocation in the first MTPJ. A rounded first
      metatarsal head would thus predispose a foot to hallux valgus. Furthermore, bone
      proliferation at the medial eminence may also lead to early hallux valgus
      development.

PMID- 25563314
TI  - Bronchial artery embolization for hemoptysis: a retrospective observational study
      of 344 patients.
AB  - BACKGROUND: Hemoptysis is a significant clinical entity with high morbidity and
      potential mortality. Both medical management (in terms of resuscitation and
      bronchoscopic interventions) and surgery have severe limitations in these
      patients population. Bronchial artery embolization (BAE) represents the first
      line treatment for hemoptysis. This article discusses clinical analysis,
      embolization approach, outcomes and complications of BAE for the treatment of
      hemoptysis. METHODS: A retrospective analysis of 344 cases, who underwent
      bronchial arteriography at Tianjin Haihe Hospital between 2006 and 2013. Several
      aspects of outcome were analyzed: Demographics, clinical presentation,
      radiographic studies, results, complications and follow-up of BAE. RESULTS: Three
      hundred and forty-four consecutive patients underwent bronchial arteriography,
      336 of 344 patients (97.7%) performed BAE; there were 1530 coils for 920 arteries
      embolized; the main responsible sources for bleeding were right bronchial artery
      (29.7%), left bronchial artery (21.6%), combined right and left bronchial trunk
      (18.4%), right intercostal arteries (13.3%); 61 patients (17.7%) had recurrent
      hemoptysis within 1 month after undergoing BAE, 74 patients (21.5%) had recurrent
      hemoptysis over 1 month after undergoing BAE; The common complications of BAE
      included subintimal dissection, arterial perforation by a guide wire, fever,
      chest pain, dyspnea, etc. The follow-up was completed in 248 patients, 28
      patients had been dead, 21 patients still bleed, 92 patients had lost to follow
      up. CONCLUSIONS: The technique of BAE is a relatively safe and effective method
      for controlling hemoptysis . The complications of BAE are rare. Although the long
      term outcome in some patients is not good, BAE may be the only life-saving
      treatment option in patients who are poor surgical candidates.

PMID- 25563315
TI  - Sequential vein bypass grafting is not associated with an increase of either in
      hospital or mid-term adverse events in off-pump coronary artery bypass grafting.
AB  - BACKGROUND: The impact of sequential vein bypass grafting on clinical outcomes is
      less known in off-pump coronary artery bypass grafting (CABG). We aimed to
      evaluate the effects of sequential vein bypass grafting on clinical outcomes in
      off-pump CABG. METHODS: From October 2009 to September 2013 at the Fuwai
      Hospital, 127 patients with at least one sequential venous graft were matched
      with 127 patients of individual venous grafts only, using propensity score
      matching method to obtain risk-adjusted outcome comparison. In-hospital
      measurement was composite outcome of in-hospital death, myocardial infarction
      (MI), stroke, requirement for intra-aortic ballon pump (IABP) assistance and
      prolonged ventilation. Major adverse cardiac events (MACEs: Death, MI or repeat
      revascularization) and angina recurrence were considered as mid-term endpoints.
      RESULTS: No significant difference was observed among the groups in baseline
      characteristics. Intraoperative mean blood flow per vein graft was 40.4 ml in
      individual venous grafts groups versus 59.5 ml in sequential venous grafts groups
      (P < 0.001). There were no differences between individual and sequential venous
      grafts groups with regard to composite outcome of in-hospital mortality, MI,
      stroke, IABP assistance and prolonged ventilation (11.0% vs. 14.2%, P = 0.45).
      Individual in-hospital measurement also did not differ significantly between the
      two groups. At about four years follow-up, the survival estimates free from MACEs
      (92.5% vs. 97.3%, P = 0.36) and survival rates free of angina recurrence (80.9%
      vs. 85.5%, P = 0.48) were similar among individual and sequential venous grafts
      groups with a mean follow-up of 22.5 months. In the Cox regression analysis,
      sequential vein bypass grafting was not identified as an independent predictor of
      both MACEs and angina recurrence. CONCLUSIONS: Compared to individual vein bypass
      grafting, sequential vein bypass grafting was not associated with an increase of
      either in-hospital or mid-term adverse events in patients undergoing off-pump
      CABG.

PMID- 25563316
TI  - Autophagy in atherosclerosis: a phenomenon found in human carotid atherosclerotic
      plaques.
AB  - BACKGROUND: Autophagy has been found to be involved in animal and cell models of
      atherosclerosis, but to date, it lacks general observation in human
      atherosclerotic plaques. Here, we investigated autophagy in smooth muscle cells
      (SMCs), endothelial cells (ECs), and macrophages in human atherosclerotic plaques
      via transmission electron microscopy (TEM), western blotting, and
      immunohistochemistry analysis. METHODS: The histopathologic morphology of these
      plaques was observed via hematoxylin and eosin staining. The ultrastructural
      morphology of the SMCs, ECs, and macrophages in these plaques was observed via
      TEM. The localization of microtubule-associated protein 1 light chain 3 (MAP1
      LC3), a relatively special maker of autophagy, in plaques was observed by double
      fluorescent immunochemistry and western blotting. RESULTS: All of these human
      atherosclerotic plaques were considered advanced and unstable in histologically
      observation. By double fluorescent immunochemistry, the expression of LC3-II
      increased in the SMCs of the fibrous cap, the macrophages, and the microvascular
      ECs of the plaque shoulders. The protein level of LC3-II by western blotting
      significantly increased in plaques compared with normal controls. In addition,
      TEM observation of plaques revealed certain features of autophagy in SMCs, ECs,
      and macrophages including the formation of myelin figures, vacuolization, and the
      accumulation of inclusions in the cytosol. These results indicate that autophagy
      is activated in SMCs, ECs, and macrophages in human advanced atherosclerotic
      plaques. CONCLUSIONS: Our study is to demonstrate the existence of autophagy in
      human atherosclerotic plaques by different methods, which may contribute to the
      development of pharmacological approaches to stabilize vulnerable and rupture
      prone lesions.

PMID- 25563317
TI  - Changes of hemoglobin and hematocrit in elderly patients receiving lower joint
      arthroplasty without allogeneic blood transfusion.
AB  - BACKGROUND: It has rarely been reported about the changes of hemoglobin (Hb) and
      hematocrit (Hct) in elderly patients receiving total knee arthroplasty (TKA) or
      total hip arthroplasty (THA). This study aimed to evaluate the changes of Hb and
      Hct after TKA or THA in elderly patients, and analyze its relationship with sex
      and type of arthroplasty. METHODS: This is a prospective cohort study, including
      107 patients receiving TKA or THA without allogeneic blood transfusion. There
      were 54 males and 53 females, with a mean age of 69.42 years. Levels of Hb and
      Hct were examined preoperatively and during the 6 months follow-up after
      operation. RESULTS: Levels of Hb and Hct decreased postoperatively and reached
      their minimum points on postoperative day 4. Thereafter, Hb and Hct recovered to
      their preoperative levels within 6-12 weeks. No significant differences in the
      levels of Hb and Hct were noticed between different sexes. THA patients showed
      significantly greater drop in Hb and Hct than TKA patients in the first 4 days
      postoperatively (P < 0.05). CONCLUSIONS: Levels of Hb and Hct decreased during
      the first 4 days after arthroplasty and gradually returned to their normal levels
      within 6-12 weeks postoperatively. THA may be associated with higher
      postoperative blood loss than TKA.

PMID- 25563318
TI  - Arthroscopic patelloplasty and circumpatellar denervation for the treatment of
      patellofemoral osteoarthritis.
AB  - BACKGROUND: Patellofemoral osteoarthritis commonly occurs in older people, often
      resulting in anterior knee pain and severely reduced quality of life. The aim was
      to examine the effectiveness of arthroscopic patelloplasty and circumpatellar
      denervation for the treatment of patellofemoral osteoarthritis (PFOA). METHODS: A
      total of 156 PFOA patients (62 males, 94 females; ages 45-81 years, mean 66
      years) treated in our department between September 2012 and March 2013 were
      involved in this study. Clinical manifestations included recurrent swelling and
      pain in the knee joint and aggravated pain upon ascending/descending stairs,
      squatting down, or standing up. PFOA was treated with arthroscopic patelloplasty
      and circumpatellar denervation. The therapeutic effects before and after surgery
      were statistically evaluated using Lysholm and Kujala scores. The therapeutic
      effects were graded by classification of the degree of cartilage defect. RESULTS:
      A total of 149 cases were successfully followed up for 14.8 months, on average.
      The incisions healed well, and no complications occurred. After surgery, the
      average Lysholm score improved from 73.29 to 80.93, and the average Kujala score
      improved from 68.34 to 76.48. This procedure was highly effective for patients
      with cartilage defects I-III but not for patients with cartilage defect IV.
      CONCLUSIONS: For PFOA patients, this procedure is effective for significantly
      relieving anterior knee pain, improving knee joint function and quality of life,
      and deferring arthritic progression.

PMID- 25563319
TI  - Prognostic factors predicting the postoperative survival period following
      treatment for primary retroperitoneal liposarcoma.
AB  - BACKGROUND: Liposarcomas, which represent 20% of all adult sarcomas, are the most
      common histological type of malignant soft tissue tumors. The aim of this study
      was to define the prognostic factors that predict the postoperative survival
      period for patients with primary retroperitoneal liposarcoma. METHODS: The
      clinical data and prognoses of 71 patients with primary retroperitoneal
      liposarcoma who were treated in the General Hospital of the People's Liberation
      Army of China between January 1, 2000 and December 31, 2007 were retrospectively
      reviewed and analyzed. RESULTS: The primary tumor from each patient was resected;
      54.9% (39/71) were deemed R0 resections, 31.0% (22/71) were R1 resections and
      14.1% (10/71) were deemed R2 resections (palliative operations). The median
      follow up was 68 months (range: 1-160 months). Of the patients who received an R1
      or R2 resection of their primary tumor, 96.7% (59/61) had tumor recurrence. The 1
      year, 3-year, and 5-year recurrence-free rates were 77.0%, 29.8% and 19.7%,
      respectively. As of April 2013, 53 of the 71 patients had died from tumor
      recurrence. The overall 1-year, 3-year, 5-year, and 10-year survival rates were
      88.7%, 76.1%, 61.7%, and 30.4%, respectively. The factors that were significantly
      associated with prognosis in the univariate analysis were age (as a categorical
      variable) (P = 0.006), modus operandi (P = 0.000), histologic subtype (P =
      0.000), tumor grade (P = 0.000), ascites (P = 0.000), postoperative metastasis (P
      = 0.000) and adjuvant therapy (P = 0.030). However, in the multivariate analysis,
      the modus operandi (P = 0.000), tumor grade (P = 0.006), ascites (P = 0.027),
      postoperative metastasis (P = 0.023) and age (as a categorical variable) (P =
      0.002) were the only significant predictors of survival. CONCLUSIONS: Complete
      resection remains the most effective method for treating liposarcoma. High grade,
      old age (>= 60 years old), postoperative metastasis, and ascites predict poor
      prognoses.

PMID- 25563320
TI  - Long non-coding RNAs expression profile in HepG2 cells reveals the potential role
      of long non-coding RNAs in the cholesterol metabolism.
AB  - BACKGROUND: Green tea has been shown to improve cholesterol metabolism in animal
      studies, but the molecular mechanisms underlying this function have not been
      fully understood. Long non-coding RNAs (lncRNAs) have recently emerged as a major
      class of regulatory molecules involved in a broad range of biological processes
      and complex diseases. Our aim was to identify important lncRNAs that might play
      an important role in contributing to the benefits of epigallocatechin-3-gallate
      (EGCG) on cholesterol metabolism. METHODS: Microarrays was used to reveal the
      lncRNA and mRNA profiles in green tea polyphenol(-)-epigallocatechin gallate in
      cultured human liver (HepG2) hepatocytes treated with EGCG and bioinformatic
      analyses of the predicted target genes were performed to identify lncRNA-mRNA
      targeting relationships. RNA interference was used to investigate the role of
      lncRNAs in cholesterol metabolism. RESULTS: The expression levels of 15 genes
      related to cholesterol metabolism and 285 lncRNAs were changed by EGCG treatment.
      Bioinformatic analysis found five matched lncRNA-mRNA pairs for five
      differentially expressed lncRNAs and four differentially expressed mRNA. In
      particular, the lncRNA AT102202 and its potential targets mRNA-3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMGCR) were identified. Using a real-time
      polymerase chain reaction technique, we confirmed that EGCG down-regulated mRNA
      expression level of the HMGCR and up-regulated expression of AT102202. After
      AT102202 knockdown in HepG2, we observed that the level of HMGCR expression was
      significantly increased relative to the scrambled small interfering RNA control
      (P < 0.05). CONCLUSIONS: Our results indicated that EGCG improved cholesterol
      metabolism and meanwhile changed the lncRNAs expression profile in HepG2 cells.
      LncRNAs may play an important role in the cholesterol metabolism.

PMID- 25563321
TI  - Xingshentongqiao decoction mediates proliferation, apoptosis, orexin-A receptor
      and orexin-B receptor messenger ribonucleic acid expression and represses mitogen
      activated protein kinase signaling.
AB  - BACKGROUND: Hypocretin (HCRT) signaling plays an important role in the
      pathogenesis of narcolepsy and can be significantly influenced by Chinese herbal
      therapy. Our previous study showed that xingshentongqiao decoction (XSTQ) is
      clinically effective for the treatment of narcolepsy. To determine whether XSTQ
      improves narcolepsy by modulating HCRT signaling, we investigated its effects on
      SH-SY5Y cell proliferation, apoptosis, and HCRT receptor 1/2 (orexin receptor 1
      [OX1R] and orexin receptor 2 [OX2R]) expression. The signaling pathways involved
      in these processes were also assessed. METHODS: The effects of XSTQ on
      proliferation and apoptosis in SH-SY5Y cells were assessed using cell counting
      kit-8 and annexin V-fluorescein isothiocyanate assays. OX1R and OX2R expression
      was assessed by quantitative real-time polymerase chain reaction analysis.
      Western blotting for mitogen-activated protein kinase (MAPK) pathway activation
      was performed to further assess the signaling mechanism of XSTQ. RESULTS: XSTQ
      reduced the proliferation and induced apoptosis of SH-SY5Y cells. This effect was
      accompanied by the upregulation of OX1R and OX2R expression and the reduced
      phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38 MAPK and
      c-Jun N-terminal kinase (JNK). CONCLUSIONS: XSTQ inhibits proliferation and
      induces apoptosis in SH-SY5Y cells. XSTQ also promotes OX1R and OX2R expression.
      These effects are associated with the repression of the Erk1/2, p38 MAPK, and JNK
      signaling pathways. These results define a molecular mechanism for XSTQ in
      regulating HCRT and MAPK activation, which may explain its ability to treat
      narcolepsy.

PMID- 25563322
TI  - Prognostic significance of tumor-infiltrating CD8+ or CD3+ T lymphocytes and
      interleukin-2 expression in radically resected non-small cell lung cancer.
AB  - BACKGROUND: Altered immunoresponse is associated with tumorigenesis and cancer
      progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 +
      T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small
      cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the
      patients. METHODS: Paraffin-embedded tissue specimens from 129 NSCLC patients
      were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2
      expression. Clinicopathological and survival data were collected and analyzed
      using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox
      regression model. RESULTS: The data showed a significant inverse association
      between CD8 + T lymphocyte levels and IL-2 expression (r = -0.927; P = 0.000) and
      between the levels of CD8 + and CD3 + T lymphocytes (r = -0.722; P = 0.000), but
      a positive association between CD3 + T lymphocyte levels and IL-2 expression (r =
      0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T
      lymphocytes and IL-2 expression were associated with tumor stage (P = 0.023,
      0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was
      associated with the patient gender (P = 0.024). In addition, the levels of CD8 +
      T lymphocytes were associated with an unfavorable 5-year OS, whereas patients
      with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing
      tumors had significantly better 5-year OS rates than patients with low levels.
      CONCLUSIONS: The levels of CD8 + T cells in tumor lesions and IL-2 expression
      were both independent predictors of OS for these NSCLC patients. Thus, the
      detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression
      could be useful to predict the prognosis of radically resected NSCLC patients.

PMID- 25563323
TI  - Population pharmacokinetics of high-dose methotrexate after intravenous
      administration in Chinese osteosarcoma patients from a single institution.
AB  - BACKGROUND: High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue
      is the gold standard therapy in the treatment of osteosarcoma. The plasma
      concentration of MTX is closely related to efficacy and toxicity. There are large
      individual differences. Many authors have described the pharmacokinetic (PK)
      profile of MTX regarding osteosarcoma under a variety of circumstances. However,
      no data concerning Chinese osteosarcoma patient PKs using the nonlinear mixed
      effects models (NONMEM) have been previously reported. The goals of this study
      were to establish the population pharmacokinetics (PPK) of HD-MTX treatment in
      Chinese osteosarcoma patients, and to explore the influence of patient covariates
      and between-occasion variability on drug disposition. METHODS: An intravenous HD
      MTX solution (10 g/m 2 ) was given 274 times to 148 osteosarcoma patients. MTX
      plasma concentrations were measured at 0, 6, 12, 24, 48 and 72 h after
      commencement of the infusion, and the fluorescence polarization immunoassay was
      used to determine MTX plasma concentrations. The PPK model and parameters were
      estimated using NONMEM software. The effects of fixed-effect factors were
      evaluated, and the final regression model was obtained. RESULTS: The following
      population parameters were obtained using a two-compartment model: CL1 (clearance
      of central compartment): (CL1 ) = CL1TV * [1 - theta CL1- MTXNUM * MTXNUM] * [1 -
      theta CL1- CrCl1 * (CrCl1 - 1.89)] * e etaCL1i (L/h). V1 (central volume): (V1)i
      = V1TV * e etaV1i (L). CL2 (clearance of peripheral compartment): (CL2)i = CL2TV
      * [1 - thetaCL2 - BODY AREA * (body area - 1.62)] * e etaCL2i (L/h). V2
      (peripheral compartment): (V2 )i = V2TV * [1 - theta V2-bodyarea * (bodyarea
      1.62)] * e etaV2i (L). The PPK parameters (RSD%) were CL1, V1, CL2 and V2 with
      values of 6.20 L/h (8.48%), 19.6 L (extremely small), 0.0172 L/h (50.9%) and
      0.515 L (39.1%), respectively. Creatinine clearance and the number of
      methotrexate chemotherapy cycles before MTX infusion had a significant effect on
      the CL1, and body surface area had a significant effect on the CL2 and the V2 (P
      < 0. 01). CONCLUSIONS: A good fit was derived for the PPK. The model could be
      used to provide guidance for MTX treatment and reduce adverse effects.

PMID- 25563324
TI  - Receptor-interacting protein 140 overexpression promotes neuro-2a neuronal
      differentiation by ERK1/2 signaling.
AB  - BACKGROUND: Abnormal neuronal differentiation plays an important role in central
      nervous system (CNS) development abnormalities such as Down syndrome (DS), a
      disorder that results directly from overexpression of genes in trisomic cells.
      Receptor-interacting protein 140 (RIP140) is significantly upregulated in DS
      brains, suggesting its involvement in DS CNS development abnormalities. However,
      the role of RIP140 in neuronal differentiation is still not clear. The current
      study aimed to investigate the effect of RIP140 overexpression on the
      differentiation of neuro-2a (N2a) neuroblastoma cells, in vitro. METHODS: Stably
      RIP140-overexpressing N2a (N2a-RIP140) cells were used as a neurodevelopmental
      model, and were constructed by lipofection and overexpression validated by real
      time polymerase chain reaction and Western blot. Retinoic acid (RA) was used to
      stimulate N2a differentiation. Combining the expression of Tuj1 at the mRNA and
      protein levels, the percentage of cells baring neurites, and the number of
      neurites per cell body was semi-quantified to determine the effect of RIP140 on
      differentiation of N2a cells. Furthermore, western blot and the ERK1/2 inhibitor
      U0126 were used to identify the specific signaling pathway by which RIP140
      induces differentiation of N2a cells. Statistical significance of the differences
      between groups was determined by one-way analysis of variance followed by the
      Dunnett test. RESULTS: Compared to untransfected N2a cells RIPl40 expression in
      N2a-RIP140 cells was remarkably upregulated at both the mRNA and protein levels.
      N2a-RIP140 cells had a significantly increased percentage of cells baring
      neurites, and numbers of neurites per cell, as compared to N2a cells, in the
      absence and presence of RA (P < 0.05). In addition, Tuj1, a neuronal biomarker,
      was strongly upregulated in N2a-RIP140 cells (P < 0.05) and phosphorylated ERK1/2
      (p-ERK1/2) levels in N2a-RIP140 cells were dramatically increased, while
      differentiation was inhibited by the ERK1/2-specific inhibitor U0126.
      CONCLUSIONS: RIP140 overexpression promotes N2a cell neuronal differentiation by
      activating the ERK1/2 pathway.

PMID- 25563325
TI  - Comparing the diagnostic criteria for gestational diabetes mellitus of World
      Health Organization 2013 with 1999 in Chinese population.

PMID- 25563326
TI  - A Chinese tuberous sclerosis complex family and a novel tuberous sclerosis
      complex-2 mutation.

PMID- 25563327
TI  - A case with ZNF198-FGFR1 gene rearrangement presenting as acute eosinophil
      myeloid leukemia.

PMID- 25563328
TI  - Adult onset retinoblastoma: a case report.

PMID- 25563329
TI  - Unusual cause of upper gastrointestinal hemorrhage: spontaneous dissection of the
      celiac trunk.

PMID- 25563331
TI  - rbamtools: an R interface to samtools enabling fast accumulative tabulation of
      splicing events over multiple RNA-seq samples.
AB  - The open source environment R isf the most widely used software to statistically
      explore biological data sets including sequence alignments. BAM is the de facto
      standard file format for sequence alignment. With rbamtools, we provide now a
      full spectrum of accessibility to BAM for R users such as reading, writing,
      extraction of subsets and plotting of alignment depth where the script syntax
      closely follows the SAM/BAM format. Additionally, rbamtools enables fast
      accumulative tabulation of splicing events over multiple BAM files.

PMID- 25563332
TI  - Co-expression analysis of high-throughput transcriptome sequencing data with
      Poisson mixture models.
AB  - MOTIVATION: In recent years, gene expression studies have increasingly made use
      of high-throughput sequencing technology. In turn, research concerning the
      appropriate statistical methods for the analysis of digital gene expression (DGE)
      has flourished, primarily in the context of normalization and differential
      analysis. RESULTS: In this work, we focus on the question of clustering DGE
      profiles as a means to discover groups of co-expressed genes. We propose a
      Poisson mixture model using a rigorous framework for parameter estimation as well
      as the choice of the appropriate number of clusters. We illustrate co-expression
      analyses using our approach on two real RNA-seq datasets. A set of simulation
      studies also compares the performance of the proposed model with that of several
      related approaches developed to cluster RNA-seq or serial analysis of gene
      expression data. AVAILABILITY AND AND IMPLEMENTATION: The proposed method is
      implemented in the open-source R package HTSCluster, available on CRAN. CONTACT:
      andrea.rau@jouy.inra.fr SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25563333
TI  - Clinicopathological analysis of near-tetraploidy/tetraploidy acute myeloid
      leukaemia.
AB  - AIMS: Near-tetraploidy/tetraploidy (NT/T) is a rare cytogenetic alteration in
      acute myeloid leukaemia (AML). NT/T-AML is categorised as complex cytogenetics
      and therefore, presumed to have an unfavourable prognosis. Our aim is to further
      characterise the clinical, morphological, cytogenetic and prognostic features of
      NT/T-AML. METHODS: We searched our cytogenetic laboratory database from 1991 to
      2012 to reveal 13 cases of NT/T-AML. Each case was evaluated with regard to its
      demographics, morphology, immunophenotype and prognosis. Specific morphological
      features included blast size, irregularity of nuclear contours, cytoplasmic
      vacuoles, and presence and lineage of dysplasia. RESULTS: Eleven men and two
      women had a median age of 68 years. Blasts were predominately large (11/13).
      Eight of 13 patients had AML with myelodysplasia-related changes. Sixty-nine per
      cent of patients achieved complete remission (CR). Median overall survival (OS)
      was 8.6 months. CR rate and median OS in cases with >= 5 cytogenetic
      abnormalities were 71% and 6 months, compared with 67% and 18.1 months in cases
      with <5 abnormalities. CONCLUSIONS: NT/T-AML occurs in older males, exhibits
      large blast size and is associated with myelodysplasia. Unlike previously
      reported data, our study reveals an overall better prognosis in this older
      population with NT/T-AML than was expected for a complex karyotype AML.
      Cytogenetic complexity independent of ploidy status did not greatly affect the
      high CR rates, but did appear to be a better estimation of prognostic risk in
      terms of median OS.

PMID- 25563334
TI  - Physical and methylation status of human papillomavirus 16 in asymptomatic
      cervical infections changes with malignant transformation.
AB  - AIMS: To evaluate how the genetic and epigenetic profile of human papillomavirus
      16 (HPV16) changes from asymptomatic cervical infections to cervical cancer
      (CaCx) development. METHODS: HPV16 physical status, methylation of its early-late
      promoters and its upstream enhancer sequences were analysed in samples from
      asymptomatic cervical infections (n=89), pre-neoplastic lesions (low and high
      grade squamous intraepithelial lesions LSIL/HSIL, n=28) and primary CaCx (n=98).
      RESULTS: In asymptomatic infection (65%, 58/89) and LSIL/HSIL (57%, 16/28)
      samples, the episomal form of HPV16 was predominant whereas integration of HPV16
      was significantly (p=0.01) higher in CaCx (59%, 57/98). The integrated viral form
      was also present in asymptomatic (27%, 24/89) and LSIL/HSIL (25%, 7/28) samples.
      The methylation of the enhancer region was comparable (29-34%) among
      asymptomatic, LSIL/HSIL and CaCx samples. The episomal form exhibited relatively
      higher methylation of the early promoter (52%) than that of the late promoter
      (40%) in asymptomatic infection but the integrated form in asymptomatic carriers
      showed the opposite methylation pattern (early promoter (42%) vs late-promoter
      (54%)). A similar pattern was observed in LSIL/HSIL samples, with comparable
      frequencies (44%) of early and late promoter methylation of the episomal form.
      However, irrespective of HPV16 physical status, higher methylation of late
      promoter than that of early promoter was observed in CaCx samples. An inverse
      correlation was observed between HPV16 integration and overall methylation of the
      early promoter-enhancer region in CaCx (p=0.05), LSIL/HSIL (p=0.09) and
      asymptomatic samples (p=0.09). CONCLUSIONS: Our study indicates that integration
      of HPV16 along with changes in methylation pattern of early and late promoters is
      essential for neoplastic transformation of asymptomatic cervical infections.

PMID- 25563335
TI  - Need for nutritional support, eating-related distress and experience of
      terminally ill patients with cancer: a survey in an inpatient hospice.
AB  - OBJECTIVES: Cancer cachexia creates a large burden for terminally ill patients
      with cancer. The main causes are a lack of knowledge of cancer cachexia and
      unsuccessful attempts to increase body weight. The role of nutritional support
      has not been clarified, and patients' eating-related distress is poorly
      understood. There has been no study investigating into needs for nutritional
      support in an inpatient hospice. The primary aim of this study was to explore
      needs for nutritional support, eating-related distress and patients' experiences.
      METHODS: A survey was conducted involving 60 patients with advanced cancer in an
      inpatient hospice. We first asked about need for nutrition therapy in the
      inpatient hospice. We then asked whether patients had unmet needs for four items.
      The last question was composed of 19 items concerning patients' experience of
      eating-related distress. RESULTS: Thirty-seven patients responded (62%). Most of
      the patients, 28 of 37 (76%), had general unmet needs for nutrition therapy for
      cancer cachexia, and more than half needed specific support, such as 'attention'
      and 'explanation'. The top 5 of the 19 items were mainly about daily diet,
      nutrition and losing weight. Of these, the top four belonged to the group of
      coping strategies and the fifth to the group of mechanisms originating from
      patients themselves. CONCLUSIONS: A number of terminally ill patients with cancer
      admitted to an inpatient hospice had need for nutritional support and experienced
      high levels of eating-related distress.

PMID- 25563336
TI  - Views and experiences of using integrated care pathways (ICPs) for caring for
      people in the last days to hours of life: results from a cross-sectional survey
      of UK professionals.
AB  - OBJECTIVES: To determine the views and experiences of health and social care
      professionals on using integrated care pathways (ICPs)for caring for people in
      the last days to hours of life. METHODS: Online cross-sectional questionnaire
      survey of UK professionals working in UK primary and secondary care settings.
      RESULTS: 1331 professionals returned completed questionnaires. Ninety-three per
      cent (1138/1228) of respondents used the Liverpool Care Pathway (LCP) or local
      variant. Eighty-eight (1089/1234) felt ICPs enabled professionals to provide
      better care for individuals and their families/carers. ICPs were viewed as
      promoting patient-centred holistic care, improving pain and symptom control,
      providing guidance and standards and improving communication with
      patients/families. Sixty-two per cent (770/1234) had no concerns regarding the
      use of ICPs. Areas of concern included incorrect use and implementation of the
      ICP, poor communication with families, junior level staff making decisions and
      insufficient education and support. CONCLUSIONS: There was strong support for
      using ICPs for caring for people in the last days to hours of life. ICPs were
      viewed as supporting high-quality patient-centred holistic care. Given the
      recommendations of the More Care Less Pathway report, those that develop the
      guidance and support that replace the LCP need to incorporate the aspects of this
      that have resulted in the benefits seen by professionals within this survey, but
      also learn from the instances where ICPs have failed to prevent poor care, or
      worse, have contributed to it.

PMID- 25563337
TI  - A methodology for the determination of fugitive dust emissions from landfill
      sites.
AB  - This study focuses on the development of a methodology for the determination of
      the contribution of fugitive dust emissions from landfill sites to ambient PM10
      concentrations and the subsequent exposure to working personnel. Fugitive dust
      emissions in landfills mainly originate from resuspension due to truck traffic on
      paved and unpaved roads and from wind-blown dust from landfill cover soil. The
      results revealed that exposure to PM10, originating from fugitive dust emissions
      in the landfill site, was exceeding the health protection standards (50 MUg m(
      3)). The higher average daily PM10 concentration (average value) for weekdays was
      equal to 275 MUg m(-3) and was computed for the areas nearby the unpaved road
      located inside the landfill facilities that lead to the landfill cell. The
      percentage contributions of road and wind-blown dust to the PM10 concentrations
      on weekdays were equal to 76 and 1%, respectively. The influence of the
      background concentration is estimated close to 23%.

PMID- 25563339
TI  - A new antimicrobial and radical-scavenging glycoside from Paullinia pinnata var.
      cameroonensis.
AB  - A new glycoside, pinnatoside A (1), together with two known compounds (2 and 3),
      were isolated from the stems of Paullinia pinnata. Their structures were
      elucidated on the basis of extensive spectroscopic analysis and chemical methods.
      Compound 1 showed significant antibacterial activity with a minimum inhibitory
      concentration (MIC) value of 1.56 MUg/mL against Escherichia coli, and 2
      displayed significant antibacterial activity with a MIC value of 1.56 MUg/mL
      against Enterobacter aerogenes and E. coli. Equally, compound 1 exhibited the
      best radical-scavenging activity (RSa50 = 25.07 +/- 0.49 MUg/mL).

PMID- 25563340
TI  - Comparison of biomass detachment from biofilms of two different Pseudomonas spp.
      under constant shear conditions.
AB  - In the context of biofilm development, detachment is of practical importance when
      placed in a biofilm management perspective. The objective of the present study
      was to examine biofilm structure and biofilm detachment under controlled
      conditions for two distinct microorganisms grown under constant shear conditions.
      Detached biofilm biomass was regularly collected and analysed over the course of
      72 h biofilm growth by Pseudomonas putida and Pseudomonas fluorescens cells, and
      biofilm structural development assessed using confocal microscopy. The two
      Pseudomonas spp., which had very similar specific growth rates in planktonic
      culture, presented notably different characteristics in terms of biofilm
      morphology but their detachment behaviours over time were very similar. These
      findings underline the intrinsic complexity of the detachment phenomenon.

PMID- 25563342
TI  - Review of drug safety and efficacy of arformoterol in chronic obstructive
      pulmonary disease.
AB  - INTRODUCTION: The global initiative for chronic obstructive lung disease
      guidelines recommend maintenance therapy using long-acting bronchodilators for
      patients with chronic obstructive pulmonary disease (COPD) who have daily
      symptoms. Arformoterol is the (R, R) - enantiomer of the racemic formoterol and
      is more potent than (R, R/ S, S) - formoterol. AREAS COVERED: Currently,
      arformoterol is one of two nebulized long-acting beta-agonists on the market. It
      has a low incidence of cardiovascular side effects with incidence of arrhythmia
      and ischemia similar to placebo. beta-adrenergic adverse effects are infrequent,
      numerically lower than formoterol, but have a quicker onset of action than
      salmeterol. There was no observed clinical tolerance over 12 months. arformoterol
      is safe in combination therapy with inhaled corticosteroids, tiotropium and
      rescue inhalers. A 12-month Phase IV trial found no increased risk of respiratory
      death or COPD exacerbation-related hospitalizations. arformoterol can potentially
      benefit patients with hyperinflation and low inspiratory flow rates. EXPERT
      OPINION: The introduction of the centers for medicare and medicaid services
      penalization for COPD readmissions may boost the appeal of long-acting
      bronchodilators as new discharge medications. With the advent of ultra long
      acting bronchodilators, its potential as a once daily agent in isolation or
      combination with these new therapies needs further study.

PMID- 25563343
TI  - Facet-dependent photoelectrochemical performance of TiO2 nanostructures: an
      experimental and computational study.
AB  - The behavior of crystalline nanoparticles depends strongly on which facets are
      exposed. Some facets are more active than others, but it is difficult to
      selectively isolate particular facets. This study provides fundamental insights
      into photocatalytic and photoelectrochemical performance of three types of TiO(2)
      nanoparticles with predominantly exposed {101}, {010}, or {001} facets, where 86
      99% of the surface area is the desired facet. Photodegradation of methyl orange
      reveals that {001}-TiO(2) has 1.79 and 3.22 times higher photocatalytic activity
      than {010} and {101}-TiO(2), respectively. This suggests that the photochemical
      performance is highly correlated with the surface energy and the number of under
      coordinated surface atoms. In contrast, the photoelectrochemical performance of
      the faceted TiO(2) nanoparticles sensitized with the commercially available MK-2
      dye was highest with {010}-TiO(2) which yielded an overall cell efficiency of
      6.1%, compared to 3.2% for {101}-TiO(2) and 2.6% for {001}-TiO(2) prepared under
      analogous conditions. Measurement of desorption kinetics and accompanying
      computational modeling suggests a stronger covalent interaction of the dye with
      the {010} and {101} facets compared with the {001} facet. Time-resolved THz
      spectroscopy and transient absorption spectroscopy measure faster electron
      injection dynamics when MK-2 is bound to {010} compared to other facets,
      consistent with extensive computational simulations which indicate that the {010}
      facet provides the most efficient and direct pathway for interfacial electron
      transfer. Our experimental and computational results establish for the first time
      that photoelectrochemical performance is dependent upon the binding energy of the
      dye as well as the crystalline structure of the facet, as opposed to surface
      energy alone.

PMID- 25563344
TI  - Solvation of actinide salts in water using a polarizable continuum model.
AB  - In order to determine how actinide atoms are dressed when solvated in water,
      density functional theory calculations have been carried out to study the
      equilibrium structure of uranium plutonium and thorium salts (UO2(2+), PuO2(2+),
      Pu(4+), and Th(4+)) both in vacuum as well as in solution represented by a
      conductor-like polarizable continuum model. This information is of paramount
      importance for the development of sensitive nanosensors. Both UO2(2+) and
      PuO2(2+) ions show coordination number of 4-5 with counterions replacing one or
      two water molecules from the first coordination shell. On the other hand, Pu(4+),
      has a coordination number of 8 both when completely solvated and also in the
      presence of chloride and nitrate ions with counterions replacing water molecules
      in the first shell. Nitrates were found to bind more strongly to Pu(IV) than
      chloride anions. In the case of the Th(IV) ion, the coordination number was found
      to be 9 or 10 in the presence of chlorides. Moreover, the Pu(IV) ion shows
      greater affinity for chlorides than the Th(IV) ion. Adding dispersion and ZPE
      corrections to the binding energy does not alter the trends in relative stability
      of several conformers because of error cancelations. All structures and
      energetics of these complexes are reported. 

PMID- 25563345
TI  - Tris(pyrazolyl)methanides of the alkaline earth metals: influence of the
      substitution pattern on stability and degradation.
AB  - Trispyrazolylmethanides commonly act as strong tridentate bases toward metal
      ions. This expected coordination behavior has been observed for tris(3,4,5
      trimethylpyrazolyl)methane (1a), which yields the alkaline-earth-metal
      bis[tris(3,4,5-trimethylpyrazolyl)methanides] of magnesium (1b), calcium (1c),
      strontium (1d), and barium (1e) via deprotonation of 1a with dibutylmagnesium and
      [Ae{N(SiMe3)2}2] (Ae = Mg, Ca, Sr, and Ba, respectively). Barium complex 1e
      degrades during recrystallization that was attempted from aromatic hydrocarbons
      and ethers. In these scorpionate complexes, the metal ions are embedded in
      distorted octahedral coordination spheres. Contrarily, tris(3
      thienylpyrazolyl)methane (2a) exhibits a strikingly different reactivity.
      Dibutylmagnesium is unable to deprotonate 2a, whereas [Ae{N(SiMe3)2}2] (Ae = Ca,
      Sr, and Ba) smoothly metalates 2a. However, the primary alkaline-earth-metal
      bis[tris(3-thienylpyrazolyl)methanides] of Ca (2c), Sr (2d), and Ba (2e)
      represent intermediates and degrade under the formation of the alkaline-earth
      metal bis(3-thienylpyrazolates) of calcium (3c), strontium (3d), and barium (3e)
      and the elimination of tetrakis(3-thienylpyrazolyl)ethene (4). To isolate
      crystalline compounds, 3-thienylpyrazole has been metalated, and the
      corresponding derivatives [(HPz(Tp))4Mg(Pz(Tp))2] (3b), dinuclear
      [(tmeda)Ca(Pz(Tp))2]2 (3c), mononuclear [(pmdeta)Sr(Pz(Tp))2] (3d), and
      [(hmteta)Ba(Pz(Tp))2] (3e) have been structurally characterized. Regardless of
      the applied stoichiometry, magnesiation of thienylpyrazole 3a with
      dibutylmagnesium yields [(HPz(Tp))4Mg(Pz(Tp))2] (3b), which is stabilized in the
      solid state by intramolecular N-H...N...H-N hydrogen bridges. The degradation of
      [Ae{C(Pz(R))3}2] (R = Ph and Tp) has been studied by quantum chemical methods,
      the results of which propose an intermediate complex of the nature
      [{(Pz(R))2C}2Ca{Pz(R)}2]; thereafter, the singlet carbenes ([:C(Pz(R))2])
      dimerize in the vicinity of the alkaline earth metal to tetrapyrazolylethene,
      which is liberated from the coordination sphere as a result of it being a very
      poor ligand for an s-block metal ion. 

PMID- 25563346
TI  - Condensation transition and forced unravelling of DNA-histone H1 toroids: a multi
      state free energy landscape.
AB  - DNA is known to condense with multivalent cations and positively charged
      proteins. However, the properties and energetics of DNA superstructures, such as
      chromatin, are poorly understood. As a model system, we investigate histone H1
      condensation of DNA with tethered particle motion and force-extension
      measurements. We show that after the addition of H1 to DNA, a concentration
      dependent lag time is followed by the DNA spontaneously condensing. The trigger
      for this condensation phase transition can be modeled as sufficient H1s having
      bound to the DNA, providing insight into the 30 nm fiber condensation upon H1
      binding. Furthermore, optical tweezers force-extension measurements of histone H1
      condensed DNA reveals a sequence of state transitions corresponding to the
      unwinding of superhelical turns. We determine the complete, experimental, multi
      state free energy landscape for the complex using Crooks fluctuation theorem. The
      measured force-versus-extension and free energy landscape are compared to
      predictions from a simple, theoretical model. This work encourages the
      theoretical description of DNA/protein structure and energetics and their role in
      chromatin and other, more complex, systems. 

PMID- 25563347
TI  - The viscoelastic properties of chromatin and the nucleoplasm revealed by scale
      dependent protein mobility.
AB  - The eukaryotic cell nucleus harbours the DNA genome that is organized in a
      dynamic chromatin network and embedded in a viscous crowded fluid. This
      environment directly affects enzymatic reactions and target search processes that
      access the DNA sequence information. However, its physical properties as a
      reaction medium are poorly understood. Here, we exploit mobility measurements of
      differently sized inert green fluorescent tracer proteins to characterize the
      viscoelastic properties of the nuclear interior of a living human cell. We find
      that it resembles a viscous fluid on small and large scales but appears
      viscoelastic on intermediate scales that change with protein size. Our results
      are consistent with simulations of diffusion through polymers and suggest that
      chromatin forms a random obstacle network rather than a self-similar structure
      with fixed fractal dimensions. By calculating how long molecules remember their
      previous position in dependence on their size, we evaluate how the nuclear
      environment affects search processes of chromatin targets. 

PMID- 25563348
TI  - Eliashberg analysis of the optical conductivity in superconducting Pr2CuOx with x
      ? 4.
AB  - Superconducting Pr(2)CuO(x), x ? 4 films with T' structure and a T(c) of 27 K
      have been investigated by millimeter-wave transmission and broadband (infrared-to
      ultraviolet) reflectivity measurements in the normal and superconducting state.
      The results obtained by both experimental methods show a consistent picture of
      the superconducting condensate formation below T(c). An Eliashberg analysis of
      the data proves d-wave superconductivity and unitary-limit impurity scattering of
      the charge carriers below T(c). The derived electron-exchange boson interaction
      spectral function I(2)chi(omega) shows only marginal changes at the
      superconducting transition with the mass enhancement factor lambda, the first
      inverse moment of I(2)chi(omega), being equal to 4.16 at 30 K and to 4.25 at 4 K.

PMID- 25563349
TI  - Climate change, water quality, and water-related diseases in the Mekong Delta
      Basin: a systematic review.
AB  - Mekong Delta Basin (MDB) is vulnerable to extreme climate and hydrological
      events. The objectives of this review are to understand of water related health
      effects exacerbated by climate change and the gaps of knowledge on the
      relationships between climate conditions, water quality, and water-related
      diseases in the MDB. The findings indicate that a few studies with qualitative
      emphases on the relationships between climate and water quality have been
      conducted in MDB, and they are insufficient to describe the pattern of climate
      disease relationship. The diseases caused by chemical contaminants in relation to
      changes of climate conditions are neglected in MDB. We suggest further studies to
      examine the influence of short-term variation of climate conditions on water
      quality and water-related diseases for the purpose of public health and medical
      prevention, and due to the trans-boundary nature of MDB, developing partnership
      in data sharing and research collaboration among MDBs countries should be
      prioritized. 

PMID- 25563350
TI  - Socioeconomic inequities in health care utilization in China.
AB  - The study assessed the present degree of inequity in health care utilization as
      well as the contributions of the main determinants in the context of expending
      health insurance coverage in China. Data were obtained from the 2008 National
      Health Services Survey (NHSS) in China. A concentration index was used to
      quantify the degree of income-related inequity in health care utilization. The
      need-standardized concentration indexes of outpatient care and inpatient care
      were 0.015 and 0.197, respectively. Income made the largest contribution to
      inequity favoring the better-off in the use of health care. The impacts of health
      insurance schemes on overall inequity varied according to the insurance
      memberships as well as types of services. The study revealed a pro-rich
      distribution of the probability of health care across income groups in China.
      Increased financial protection ability of medical insurance system remains a
      vital cornerstone to tackle the health care utilization inequity. 

PMID- 25563351
TI  - Reducing Medical Errors in Primary Care Using a Pragmatic Complex Intervention.
AB  - This study aimed to develop an intervention to reduce medical errors and to
      determine if the intervention can reduce medical errors in public funded primary
      care clinics. A controlled interventional trial was conducted in 12 conveniently
      selected primary care clinics. Random samples of outpatient medical records were
      selected and reviewed by family physicians for documentation, diagnostic, and
      management errors at baseline and 3 months post intervention. The intervention
      package comprised educational training, structured process change, review
      methods, and patient education. A significant reduction was found in overall
      documentation error rates between intervention (Pre 98.3% [CI 97.1-99.6]; Post
      76.1% [CI 68.1-84.1]) and control groups (Pre 97.4% [CI 95.1-99.8]; Post 89.5%
      [85.3-93.6]). Within the intervention group, overall management errors reduced
      from 54.0% (CI 49.9-58.0) to 36.6% (CI 30.2-43.1) and medication error from 43.2%
      (CI 39.2-47.1) to 25.2% (CI 19.9-30.5). This low-cost intervention was useful to
      reduce medical errors in resource-constrained settings. 

PMID- 25563352
TI  - Regulation of TRH neurons and energy homeostasis-related signals under stress.
AB  - Energy homeostasis relies on a concerted response of the nervous and endocrine
      systems to signals evoked by intake, storage, and expenditure of fuels.
      Glucocorticoids (GCs) and thyroid hormones are involved in meeting immediate
      energy demands, thus placing the hypothalamo-pituitary-thyroid (HPT) and
      hypothalamo-pituitary-adrenal axes at a central interface. This review describes
      the mode of regulation of hypophysiotropic TRHergic neurons and the evidence
      supporting the concept that they act as metabolic integrators. Emphasis has been
      be placed on i) the effects of GCs on the modulation of transcription of Trh in
      vivo and in vitro, ii) the physiological and molecular mechanisms by which acute
      or chronic situations of stress and energy demands affect the activity of
      TRHergic neurons and the HPT axis, and iii) the less explored role of non
      hypophysiotropic hypothalamic TRH neurons. The partial evidence gathered so far
      is indicative of a contrasting involvement of distinct TRH cell types, manifested
      through variability in cellular phenotype and physiology, including rapid
      responses to energy demands for thermogenesis or physical activity and
      nutritional status that may be modified according to stress history. 

PMID- 25563354
TI  - Ecdysone receptor in the mud crab Scylla paramamosain: a possible role in
      promoting ovarian development.
AB  - In arthropods, it is known that ecdysteroids regulate molting, limb regeneration,
      and reproduction through activation of the ecdysone receptor (EcR). However, the
      ecdysteroid signaling pathway for promotion of ovarian development in crustaceans
      is still unclear. In this study, three cDNA isoforms of EcR were cloned from the
      mud crab Scylla paramamosain. qRT-PCR revealed that the SpEcR mRNA was abundant
      in the eyestalk, ovary and epidermis. During ovarian development, the SpEcR
      transcripts increased from stage I (undeveloped stage) and reached a peak at
      stage IV (late vitellogenic stage) before dropping to a lower level at stage V
      (mature stage). Meanwhile, levels of 20-hydroxyecdysone (20E) in the hemolymph,
      detected by HPLC-MS, displayed a similar pattern of increase with ovarian
      development. Results from in situ hybridization indicated that SpEcR mRNA was
      present in the follicular cells during vitellogenesis. Results from in vivo
      experiments revealed that 20E at 0.2 MUg/g body weight significantly stimulated
      the expression of SpEcR and vitellogenin (SpVg) in female crabs during the early
      vitellogenic stage but not during the previtellogenic stage. This was confirmed
      by results from in vitro experiments which indicated that SpEcR and SpVg
      expression levels were significantly upregulated in early vitellogenic ovarian
      explants incubated with 5.0 MUM 20E at 3 and 6 h but not in previtellogenic
      ovarian explants. Finally, results from in vitro gene silencing experiments
      indicated that the expression of SpEcR and SpVg in the ovary was significantly
      inhibited by SpEcR dsRNA. All these results together indicated that in S.
      paramamosain, 20E, and SpEcR, located in the follicular cells, play important
      roles in the promotion of ovarian development via regulating the expression of
      SpVg. 

PMID- 25563353
TI  - Androgen receptor in human endothelial cells.
AB  - Androgen receptor (AR) is a ligand-inducible transcription factor, and a member
      of the steroid-thyroid-retinoid receptor superfamily, that mediates the
      biological effects of androgens in a wide range of physiological and pathological
      processes. AR expression was identified in vascular cells nearly 20 years ago,
      and recent research has shown that AR mediates a variety of actions of androgens
      in endothelial and vascular smooth muscle cells. In this mini-review, we review
      evidence indicating the importance of AR in human endothelial cell (HUVEC)
      homeostatic and pathogenic processes. Although a role for AR in the modulation of
      HUVEC biology is evident, the molecular mechanisms by which AR regulates HUVEC
      homeostasis and disease processes are not fully understood. Understanding these
      mechanisms could provide critical insights into the processes of pathogenesis of
      diseases ranging from cardiovascular disease to cancer that are major causes of
      human morbidity and mortality. 

PMID- 25563355
TI  - Re-Treatment with EGFR-TKIs in NSCLC Patients Who Developed Acquired Resistance.
AB  - In the era of personalized medicine, epidermal growth factor receptor (EGFR)
      inhibition with tyrosine kinase inhibitor (TKI) has been a mainstay of treatment
      for non-small cell lung cancer (NSCLC) patients with an EGFR mutation. Acquired
      resistance, especially substitution of methionine for threonine at position 790
      (T790M), which has accounted for more than half of the cases, developed
      inevitably in patients who were previously treated with EGFR-TKI. At present,
      there is no standard treatment for patients who have developed a resistance to
      EGFR-TKI. Several strategies have been developed or suggested to treat such
      patients. This article aimsto review the EGFR-TKI re-treatment strategy and the
      efficacy of different generations of EGFR-TKIs in patients with acquired
      resistance to prior EGFR-TKI. 

PMID- 25563356
TI  - A systematic review and meta-analysis of mobile devices and weight loss with an
      intervention content analysis.
AB  - INTRODUCTION: Overweight and obesity constitute leading global public health
      challenges. Tackling overweight and obesity by influencing human behaviour is a
      complex task, requiring novel emerging health psychology interventions. The aims
      of this review will be to determine whether mobile devices induce weight loss and
      improvements in diet and physical activity levels when compared with standard
      controls without a weight loss intervention or controls allocated to non-mobile
      device weight loss interventions. METHODS: A systematic review on mobile devices
      and weight loss was conducted. The inclusion criteria were all randomized
      controlled trials with baseline and post-intervention weight measures in adult
      subjects >18 years of age without pre-specified co-morbidities. Mobile device
      specifications included modern, portable devices in the form of smartphones,
      PDAs, iPods, and Mp3 players. Cohen's d for standardized differences in mean
      weight loss was calculated. A random effects meta-analysis was generated using
      Comprehensive meta-analysis software. Theories and intervention content were
      coded and analysed. RESULTS: A total of 17 studies were identified, of which 12
      were primary trials and 5 were secondary analyses. The meta-analysis generated a
      medium significant effect size of 0.430 (95% CI 0.252-0.609) (p-value <= 0.01),
      favouring mobile interventions. Throughout the systematic review, mobile devices
      were found to induce weight loss relative to baseline weight. When comparing them
      with standard no intervention controls as well as controls receiving non-mobile
      weight loss interventions, results favoured mobile devices for weight loss.
      Reductions in Body mass index, waist circumference, and percentage body fat were
      also found in the review. Improvements in the determinants of weight loss in the
      form of improved dietary intake and physical activity levels were also found.
      Theory appears to largely inform intervention design, with the most common
      theories being Social Cognitive Theory, Elaboration Likelihood Theory, Control
      Theory, and Goal Theory. The use of behavioural change techniques was widespread
      across the studies, with a minimum of five per intervention. CONCLUSION: Mobile
      devices appear to induce positive changes in the behavioural determinants of
      weight and subsequently are associated with weight loss. Mobile device
      interventions are heavily informed by theory and behaviour change techniques. The
      use of theory appears to effectively enhance levels of constructs targeted by
      interventions.

PMID- 25563357
TI  - Non-Small Cell Lung Cancer beyond Biomarkers: The Evolving Landscape of Clinical
      Trial Design.
AB  - The approval of EGFR and ALK directed tyrosine kinase inhibitors materialized the
      concept of tailoring therapy on the basis of specific biomarkers for treating
      patients with NSCLC. Research for other biologics, although demonstrating
      clinical benefit, has been less successful so far for producing biomarkers that
      predict response. Blocking angiogenesis is the prototype for the agents that
      belong in the latter group that target specific molecules, yet they are currently
      approved for relatively unselected groups of patients. In order to meet the goal
      of personalizing care in the various settings of NSCLC, a wealth of biologics and
      compounds are currently being tested in clinical trials in different phases of
      clinical development. In a subset of the relevant studies, a biomarker
      perspective is appreciated. This review summarizes the clinical rationale of the
      major ongoing phase II and III NSCLC studies that employ targeting specific
      molecules with novel agents, as well as innovative strategies, and includes a
      comparative discussion of the different designs. 

PMID- 25563358
TI  - Next generation sequencing as an aid to diagnosis and treatment of an unusual
      pediatric brain cancer.
AB  - Classification of pediatric brain tumors with unusual histologic and clinical
      features may be a diagnostic challenge to the pathologist. We present a case of a
      12-year-old girl with a primary intracranial tumor. The tumor classification was
      not certain initially, and the site of origin and clinical behavior were unusual.
      Genomic characterization of the tumor using a Clinical Laboratory Improvement
      Amendment (CLIA)-certified next-generation sequencing assay assisted in the
      diagnosis and translated into patient benefit, albeit transient. Our case argues
      that next generation sequencing may play a role in the pathological
      classification of pediatric brain cancers and guiding targeted therapy,
      supporting additional studies of genetically targeted therapeutics. 

PMID- 25563359
TI  - mHealth for Smoking Cessation Programs: A Systematic Review.
AB  - mHealth transforms healthcare delivery around the world due to its affordability
      and right time availability. It has been used for delivery of various smoking
      cessation programs and interventions over the past decade. With the proliferation
      of smartphone usage around the world, many smartphone applications are being
      developed for curbing smoking among smokers. Various interventions like SMS,
      progress tracking, distractions, peer chats and others are being provided to
      users through smartphone applications. This paper presents a systematic review
      that analyses the applications of mobile phones in smoking cessations. The
      synthesis of the diverse concepts within the literature on smoking cessations
      using mobile phones provides deeper insights in the emerging mHealth landscape. 

PMID- 25563360
TI  - Surveillance recommendations in reducing risk of and optimally managing breast
      cancer-related lymphedema.
AB  - Breast cancer survivors are at increased risk for the development of breast
      cancer-related lymphedema (BCRL), a chronic, debilitating, and disfiguring
      condition that is progressive and requires lifelong self-management of symptoms.
      It has been reported that over 40% of the 2.5 million breast cancer survivors in
      the United States may meet the criteria for BCRL during their lifetimes. Ongoing
      surveillance, beginning with pre-operative assessment, has been effective in
      identifying subclinical lymphedema (LE). A prospective model for surveillance is
      necessary in order to detect BCRL at an early stage when there is the best chance
      to reduce risk or slow progression. Physical methods for monitoring and
      assessment, such as circumferential arm measures, perometry, bioimpedance;
      exercise programs; prophylactic and early-intervention compression garments; and
      referral for complete decongestive therapy are all interventions to consider in
      the development of a BCRL surveillance program. In addition, supportive-educative
      programs and interactive engagement for symptom self-management should also be
      implemented. The importance of interdisciplinary collaboration is integral to the
      success of an effective personalized medicine program in breast cancer-related
      lymphedema surveillance. 

PMID- 25563362
TI  - The contribution of TGF-beta in Epithelial-Mesenchymal Transition (EMT): Down
      regulation of E-cadherin via snail.
AB  - TGF-beta plays a central role in epithelial-mesenchymal transition (EMT), which
      is a highly conserved and reversible process that governs tumor development,
      invasion and metastasis. Through this transition, the epithelial cell acquires a
      migratory behavior which allows it to move away from the cell community and to
      integrate into the surrounding tissue. The cells lost epithelial phenotypes
      including the change of cell polarity and the loss of specialized cell-cell
      contacts, which related with the shortage of E-cadherin directly. The increasing
      reports indicated that TGF-beta down-regulated the expression of E-cadherin
      through snail signaling pathway, which played an important role in the
      development of EMT. In this review, we summarized the contribution of TGF-beta in
      EMT and discussed the molecular mechanism of snail signaling participating in the
      regulation of E-cadherin triggered by TGF-beta. KEYWORDS: TGF-beta, Epithelial
      mesenchymal-transition (EMT), snail family, E-cadherin.

PMID- 25563363
TI  - Cathepsin S as a cancer target.
AB  - Cathepsin S is a lysosomal enzyme that belongs to the papain family of cysteine
      proteases. Multiple studies indicate that cathepsin S acts not only as a crucial
      role in antigen presentation but also as an important protagonist of cancers.
      Cathepsin S has been shown to participate in dissolution and remodelling of
      connective tissue and basement membranes, resulting in the process of tumor
      growth, invasion, metastasis and angiogenesis. Therefore, cathepsin S has been
      suggested as a potential therapeutic target in cancer therapy. In the present
      study, we review the rapidly advancing field of cathepsin S in cancer therapy,
      highlighting the specific roles of cathepsin S in cancer. KEYWORDS: Cathepsin S,
      cancer, combined chemotherapy, inhibitors.

PMID- 25563364
TI  - Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast
      cancer cells with saponin extract from Tribulus terrestris.
AB  - Saponins are natural substances produced by a large number of plants, one of
      which is Tribulus terrestris L. (TT). They have been reported to possess an
      antitumor activity exerted by regulating various signaling pathways in the cell.
      Although the mechanisms of action of saponin extracts from various plants have
      been widely studied, limited data are available about TT. The present study aimed
      to analyze the impact of saponin extract from TT on cell processes in breast
      carcinoma cell lines. The variations in expression of a group of 32 selected
      genes were examined by real-time PCR after saponin treatment of MCF7 and MCF10A
      cell lines. Only three genes - CXCR4, CCR7 and BCL2, showed changes in their mRNA
      levels after the application of the herb extract. While CXCR4 expression was
      reduced in both cell lines, CCR7 and BCL2 levels decreased only in tumorigenic
      MCF7 cells, implying cell-specificity of the saponin action. Our results
      suggested that TT extract containing saponins was likely to affect the processes
      of apoptosis and metastasizing of cancer cells. Further in vivo studies will show
      its applicability as an anticancer therapeutic agent. KEYWORDS: saponins,
      Tribulus terrestris, breast cancer, CXCR4, CCR7, BCL2.

PMID- 25563361
TI  - KUD773, a phenylthiazole derivative, displays anticancer activity in human
      hormone-refractory prostate cancers through inhibition of tubulin polymerization
      and anti-Aurora A activity.
AB  - BACKGROUND: Hormone-refractory prostate cancer (HRPC), which is resistant to
      hormone therapy, is a major obstacle in clinical treatment. An approach to
      inhibit HRPC growth and ultimately to kill cancers is highly demanded. RESULTS:
      KUD773 induced the anti-proliferative effect and subsequent apoptosis in PC-3 and
      DU-145 (two HRPC cell lines); whereas, it showed less active in normal prostate
      cells. Further examination showed that KUD773 inhibited tubulin polymerization
      and induced an increase of mitotic phosphoproteins and polo-like kinase 1 (PLK1)
      phosphorylation, indicating a mitotic arrest of the cell cycle through an anti
      tubulin action. The kinase assay demonstrated that KUD773 inhibited Aurora A
      activity. KUD773 induced an increase of Cdk1 phosphorylation at Thr(161) (a
      stimulatory phosphorylation site) and a decrease of phosphorylation at Tyr(15)
      (an inhibitory phosphorylation site), suggesting the activation of Cdk1. The data
      were substantiated by an up-regulation of cyclin B1 (a Cdk1 partner).
      Furthermore, KUD773 induced the phosphorylation and subsequent down-regulation of
      Bcl-2 and activation of caspase cascades. CONCLUSIONS: The data suggest that
      KUD773 induces apoptotic signaling in a sequential manner. It inhibits tubulin
      polymerization associated with an anti-Aurora A activity, leading to Cdk1
      activation and mitotic arrest of the cell cycle that in turn induces Bcl-2
      degradation and a subsequent caspase activation in HRPCs.

PMID- 25563365
TI  - Knockdown of NF-kappaB p65 subunit expression suppresses growth of nude mouse
      lung tumor cell xenografts by activation of Bax apoptotic pathway.
AB  - Nuclear factor-kappaB (NF-kappaB) is an important transcriptional factor and
      regulates a variety of pathophysiologic process involved in cell survival and
      death. The present study assesses the effects of NF-kappaB p65 subunit knockdown
      in suppression of nude mouse lung tumor cell xenografts and understands the
      underlying molecular events.A nude mouse Lewis lung carcinoma cell xenograft
      model was established and the mice were intraperitoneally injected with NF-kappaB
      p65 siRNA and sacrificed after two weeks of tumor cell injection. Tumor
      xenografts were harvested for TUNEL, Western blot, and qRT-PCR analyses.Compared
      to the PBS-treated or the negative control (NC) siRNA-treated mice, tumor
      xenograft weight and volume was significantly decreased in the NF-kappaB p65
      siRNA-treated mice. The TUNEL positive (apoptosis) cells in xenograft sections
      were 45 +/- 5 in PBS and 38 +/- 3 in NC siRNA, but increased to 271 +/- 11 in p65
      siRNA-treated mice. Compared to the PBS or the NC mice, levels of Bax mRNA and
      protein in tumor xenografts were significantly upregulated in p65 siRNA-treated
      mice. Knockdown of NF-kappaB p65 subunit expression significantly inhibited the
      growth of nude mouse Lewis tumor cell xenografts by induction of tumor cell
      apoptosis and significantly up-regulation of pro-apoptotic protein Bax
      expression. Future study will confirm the current data and targeting NF-kappaB
      p65 subunit expression as a potential therapeutic strategy in treating human lung
      cancer. KEYWORDS: NF-kappaB, lung cancer, apoptosis, small interfering RNA,
      xenografts.

PMID- 25563367
TI  - Microarray data analysis reveals differentially expressed genes in prolactinoma.
AB  - Gene expression profiles of prolactinomas were compared with those of normal
      pituitary glands to identify differentially expressed genes (DEGs). Protein
      protein interaction (PPI) analysis and protein complex prediction were performed
      to reveal the cross-talk between these genes and molecular mechanisms underlying
      the disease. Microarray data were downloaded from Gene Expression Omnibus. DEGs
      were screened using GEO2R and false discovery rate (FDR) < 0.05 was set as the
      cut-off. Protein-protein interaction (PPI) network was constructed with
      information from STRING and significant KEGG pathways were unveiled. Protein
      complexes were predicted using ClusterONE from Cytoscape and then validated in
      terms of pathways, protein domain, cellular localization and literatures. A 
      total of 1712 genes (1911 probes) were found to be differentially expressed in
      prolactinoma. Interactions were identified among 121 protein products. Nineteen
      significant pathways (FDR< 0.05) were acquired and pathways in cancer was the top
      one. Pathways linked to myeloid leukemia and tryptophan metabolism were also
      enriched in the DEGs. Four protein complexes were predicted and then validated.
      They were associated with focal adhesion, cytoskeleton, metabolism of tryptophan,
      arginine and proline as well as aldehyde dehydrogenases. They might play
      important roles in the pathogenesis of prolactinoma. In present study, not only
      DEGs were provided, but also PPIs and protein complexes were discussed. These
      findings promoted the knowledge about prolactinoma and provided novel candidate
      targets for the therapy development of prolactinoma. KEYWORDS: prolactinoma,
      differentially expressed genes, protein-protein interaction network, protein
      complex.

PMID- 25563368
TI  - FOXM1 overexpression is associated with cisplatin resistance in non-small cell
      lung cancer and mediates sensitivity to cisplatin in A549 cells via the
      JNK/mitochondrial pathway.
AB  - The Forkhead box M1 transcription factor (FoxM1) is essential for DNA replication
      and mitosis, and has important role in cell proliferation and apoptosis. To
      assess the role of FoxM1 in chemoresistance, we investigated FoxM1 protein
      expression and the correlation between FoxM1 expression, sensitivity to cisplatin
      based therapy, and the survival of non-small cell lung cancer (NSCLC) patients.
      We generated a cisplatin-resistant lung cancer cell line (A549/CDDP) that showed
      elevated expression levels of FoxM1 protein and mRNA relative to those of the
      parental A549 cells. We investigated the effect of the knockdown or
      overexpression of FoxM1 on the sensitivity to cisplatin and the possible
      signaling transduction pathways in these cells. Our results revealed that the
      positive expression rate of FoxM1 in NSCLC was associated with chemosensitivity
      to cisplatin and a poor prognosis. When the expression of FoxM1 was inhibited by
      RNA interference, the sensitivity to cisplatin was enhanced. Inversely, in FoxM1
      overexpressing cell models, we observed a reduced sensitivity to cisplatin.
      Moreover, we showed that the downregulation of FoxM1 enhanced cisplatin-induced
      A549/CDDP cell apoptosis through the activation of the c-Jun NH2-terminal kinase
      (JNK)/mitochondrial pathway. These results suggest that FoxM1 plays a critical
      role in chemoresistance to cisplatin and that FoxM1 depletion may be a promising
      approach to lung cancer therapy. KEYWORDS: FoxM1, cisplatin, drug resistance, non
      small cell lung cancer, A549, JNK/mitochondrial pathway.

PMID- 25563366
TI  - Fn14 receptor promotes invasive potential and metastatic capacity of non-small
      lung adenocarcinoma cells through the up-regulation of integrin alpha6.
AB  - Lung cancer is one of the leading cause of cancer-related death around the world
      with the majority of diagnoses being non-small cell lung cancer (NSCLC). Given
      the poor survival rate and efficacy of current therapy for NSCLC, there is a need
      to identify and develop new therapeutic targets for treatment. We have observed
      significantly up-regulated levels of Fn14 in clinical samples of lung cancer
      relative to normal adjacent tissue. However, the functional role of Fn14 in these
      tumors is not understood yet. We used RT-PCR to establish the Fn14 expression
      profile in various NSCLC cell lines. Using isogenic variants of H460 NSCLC cell
      line with low, intermediate and high Fn14 expression as a cellular model, we
      determined that increased levels of integrin alpha6 in cells over-expressing Fn14
      is suggestive of an important role of alpha6beta1-fn14 interactions in motility
      of lung carcinoma and formation of metastases. Enhanced levels of Fn14 correlated
      with higher tumor cell migration and invasion in an MMP-1 dependent manner. Cells
      over-expressing Fn14 showed increased in vivo tumor formation with metastatic
      capacity to lymph nodes, lungs and liver. Thus, this research may be a step
      toward developing improved treatment strategies for NSCLC by improved detection
      and inhibition of metastases. KEYWORDS: Fn14, TNFRSF12A, non-small cell lung
      cancer, H460 cells, motility, tumor formation and metastasis, integrin alpha6.

PMID- 25563369
TI  - Association of PIK3CA gene mutations with head and neck squamous cell carcinomas.
AB  - The Phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) is an
      important regulator of cell signaling pathways in human cancers. Mutations in
      PIK3CA were found to be associated with more aggressive clinical outcome and
      aberrant activation of cellular mechanisms in cancers. Hence the present study
      aimed to understand the mutations in the PIK3CA gene in head and neck squamous
      cell carcinomas (HNSCC). After the approval of the Institutional Ethics Committee
      we recruited 129 HNSCC patients and 150 healthy controls for screening of
      mutations in the helical (exon9) and kinase domain (exon 20) of the PIK3CA gene
      using PCR, SSCP and Sanger Sequencing. We found about 60.46% of HNSCC patients
      and 26% of controls with the following mutations 1634A>C (E545A) and 3075C>T
      (T1025T) in the helical and kinase domains of PIK3CA. Both these mutations
      1634A>C and 3075C>T were more prominent in oral cancers, advanced stages of HNSCC
      and tobacco plus alcohol habits (p<0.05). Hence, we conclude that the
      distribution of mutations of PIK3CA in HNSCC were associated with demographic
      (tobacco and alcohol) and clinical parameters (advanced stage, primary site) of
      HNSCC. It is possible that when this pathway is overactive due to mutations, it
      may reduce apoptosis and allow proliferation of the tumor cells. Therefore we
      propose that these mutations may serve as prognostic biomarkers, and can also be
      proposed as novel therapeutic targets for HNSCC. KEYWORDS: PI3 kinase, gene
      polymorphism, helical domain, kinase domain, oral cancers.

PMID- 25563370
TI  - Overexpression of Survivin mutant Thr34Ala induces apoptosis and inhibits gastric
      cancer growth.
AB  - Survivin is highly expressed in human gastric cancer and correlated with
      chemoresistance and poor prognosis. In this study, we explored the effect of
      adeno-associated virus (AAV)-mediated survivin dominant mutant Thr34Ala (rAAV-Sur
      Mut(T34A)) on gastric cancer growth. AAV-Sur-Mut (T34A) virus was generated and
      purified using the AAV vector pAM/CAG-WPRE.poly(A) vector. Cell proliferation was
      determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide
      (MTT) Assay. Apoptosis was determined by Flow cytometry and Terminal
      deoxynucleotidyl transferase dUTP nick end labeling. Gene expression was
      determined by Western blot and immunohistochemistry. Tumor growth was evaluated
      using a xenograft mouse model. Overexpression of survivin promoted cell growth of
      gastric cancer cells. Infection of rAAV-Sur-Mut(T34A) virus inhibited cell
      proliferation, induced apoptosis and sensitized gastric cancer cells to 5
      Fluorouracil in vitro. Treatment of rAAV-Sur-Mut(T34A) significantly inhibited
      cell proliferation, induced apoptosis and inhibited gastric cancer growth in
      vivo. Our results suggest that the combination of rAAV-Sur-Mut(T34A) and
      chemotherapy may be a new approach for gastric cancer therapy. KEYWORDS:
      Survivin, survivin mutant T34A, adeno-associated virus, gastric cancer,
      apoptosis, gene therapy.

PMID- 25563371
TI  - Correlation of carbonic anhydrase IX expression with clinico-morphological
      parameters, hormonal receptor status and HER-2 expression in breast cancer.
AB  - The hypoxia-inducible protein carbonic anhydrase IX is widely expressed in most
      human cancers, including breast carcinomas. CA IX attracts significant interest
      due to its strong association with neoplasms and its absence from corresponding
      normal tissues, suggesting its potential to serve as a promising diagnostic
      biomarker. This protein comes into the limelight also as a valuable prognostic
      and predictive parameter. Immunohistochemically, we examined the expression of
      this protein in 84 cases of invasive breast carcinoma to determinate the
      association with clinico-morphological and biological parameters such as age of
      patients, grade, stage and size of primary tumor, lymph node metastasis, vascular
      invasion as well as hormone receptor status and HER-2 expression. In each case,
      the subcellular localization of CA IX antigen, the intensity of staining and the
      percentage of labeled cells were assessed. Overall, CA IX was expressed in 34
      cases (40.5%). The statistical analysis revealed a significant correlation
      between subcellular localization of CA IX and the age of patients. Furthermore,
      significant correlations were also found between the grade, estrogen and
      progesterone status and all immunohistochemical characteristics of CA IX
      expression (the subcellular localization of CA IX antigen, the intensity of
      staining and the percentage of labeled cells). We point out that mostly membrane
      or combined membrane and cytoplasmic positivity together with a higher intensity
      of CA IX immunoreactivity are associated with poor prognostic parameters, such as
      tumor grade 3 and also with negative estrogen and progesterone receptor status
      which may influence therapeutic approach. However, no significant correlations
      were shown with remaining clinico-morphological and biological parameters. We
      next investigate the relationship between CA IX expression in the group of
      invasive ductal carcinomas and the group of invasive lobular carcinomas and other
      less frequent types of breast carcinoma. There was, however, no significant
      difference. Our results suggest that moderate to strong membrane and combined
      membrane and cytoplasmic localization of CA IX may represent a valuable tumor
      biomarker as well as a promising prognostic and predictive parameter in invasive
      breast cancer. KEYWORDS: breast carcinoma, carbonic anhydrase IX,
      immunohistochemistry, clinico-morphological and biological parameters.

PMID- 25563372
TI  - Intracellular distribution of 3,6-bis(3-alkylguanidino)acridines determines their
      cytotoxicity.
AB  - Cytotoxicity of two derivatives of 3,6-bis(3-alkylguanidino)acridines (GNDAs;
      pentyl- and hexyl-GNDA) was determined against three cell lines: a murine
      immortalized fibroblast cell line NIH-3T3, a human ovarian carcinoma cell line
      A2780, and a human neuroblastoma cell line SH-SY5Y. We found out that these GNDAs
      were cytotoxic against A2780 and NIH-3T3 cells but they showed only a marginal
      cytotoxicity against neuroblastoma cells SH-SY5Y. To explain differences in
      cytotoxicity, intracellular distribution of GNDAs was monitored. GNDAs were
      accumulated in A2780 and NIH-3T3 cells in the nuclei (fluorescence microscopy).
      In contrast to these cell lines, in SH-SY5Y cells, GNDAs were localized outside
      of the nuclei, at the plasma membrane and surroundings, extending also to the
      cytosol. This distribution of GNDAs was confirmed by an ImageStream Flow
      Cytometer. Acetylcholinesterase (AChE) activity in the SH-SY5Y cells decreased
      upon incubation with GNDAs. Kinetic studies showed that GNDAs were able to
      inhibit AChE by the same mode as tacrine (9-amino-1,2,3,4-tetrahydroacridine), a
      known inhibitor of AChE. A low cytotocity of GNDAs against SH-SY5Y cells could be
      caused by their affinity to AChE (the enzyme is localized mainly at the plasma
      membrane). The interaction of GNDAs with AChE may affect their intracellular
      distribution and consequently the cytotoxicity. KEYWORDS: acetylcholinesterase,
      acridine, neuroblastoma cell line SH-SY5Y.

PMID- 25563373
TI  - Associations between the Expression of micro-RNA 214 and clinicopathologic
      parameters of glioma.
AB  - It have been reported that miR-214 reduction facilitates UBC9 expression and is
      involved in the regulation of glioma cell proliferation. However, the specific
      role of miR-214 in glioma remains unknown. Thus, we investigated the relationship
      between expression level of miR-214 and clinico- pathological features and
      prognosis in patients with glioma in a follow-up of 5years. We used Chi-square
      tests for the categorical data and Mann-Whitney tests for continuous data.
      Survival time was calculated from the date of glioma diagnosis to the date of
      death or last follow-up. Survival analysis was estimated using the Kaplan-Meier
      method, log-rank test, and Cox-proportional hazards regression model. In the
      present study, we confirmed that the expression level of miR-214 was increased in
      glioma tissues compared with the non-neoplastic brain tissues. Next, the Kaplan
      Meier analysis revealed that glioma patients with high miR-214 expression tend to
      have poorer overall survival. In addition, the multivariate analysis clearly
      demonstrated that high miR-214 expression was a statistically significant risk
      factor affecting overall survival in glioma patients, suggesting that miR-214
      upregulation in gliomas is not only in a grade-dependent fashion, it is also a
      predictor of overall survival. Finally, subgroup analyses showed the significant
      prognostic value of miR-214 upregulation for glioma patients in those with low
      and high pathological grade. The results of this study showed that miR-214 was up
      regulated in glioma tissues. The expression of miR-214 was associated with the
      pathological stages of glioma. The results of 5-years follow-up showed that the
      expression level of miR-214 is a significant prognostic factor for patients with
      glioma. KEYWORDS: miR-214, glioma, prognosis.

PMID- 25563374
TI  - Prognostic and predictive molecular biological markers in prostate cancer -
      significance of expression of genes PCA3 and TMPRSS2.
AB  - Prostate specific antigen and digital rectal examination have low specificity for
      detecting prostate cancer and they poorly predict the presence of aggressive
      disease. We present recent findings on PCA3 and TMPRSS:ERG fusion and assessed
      the relationship between PSA, urine PCA3 and TMPRSS2:ERG and corelation with
      pathological findings. We tested the PCA3 score in two groups. The first
      comprised 96 men treated in urology out-patient units with suspicion of prostate
      cancer, who had elevated PSA and/or positive DRE. The second group comprised 28
      patients, who were treated by radiation for localised prostate cancer, and whose
      PCA3 was regularly monitored. A further cohort comprised patients with already
      diagnosed tumors, who had undergone radical prostatectomy. With these, using
      histopathological samples, we examined samples of the TMPRSS2:ERG fusion gene and
      compared the results with Gleason score values and level of PSA. We also examined
      the TMPRSS2:ERG gene in patients who had positive biopsy. Part of the genetical
      analysis was also an examination of the MSMB gene.The sensitivity of PCA3 testing
      was 66.7% and the specificity 78.5%. TMPRSS2:ERG gene was correllated with the
      Gleason score. Neither the TMPRSS2:ERG (p=0.13) nor the MSMB (p=0.556) genotype
      had an influence on the value of the Gleason score. However a difference was
      found between the homozygote and wild type (WT) in the TMPRSS2 gene.FISH analysis
      of TMPRSS/ERG gene fusion was evaluated as positive in 8 (36.8%) of the
      biopsically verified tumors and in 20 (37.3%) of the evaluated patients after
      RAPE of parafin slicing.We did not confirm a corellation between fusion and
      Gleason score (p=0.29).PCA3, with its higher sensitivity in comparison with PSA,
      is more useful for eventual screening examination. Identification of further
      molecular markers such as TMPRSS2, may be very promising ways to determine
      further prognosis of patients with prostate cancer. KEYWORDS: prostate cancer,
      PSA, PCA3.

PMID- 25563375
TI  - Antioxidant defense system in prostate adenocarcinoma and benign prostate
      hyperplasia of elderly patients.
AB  - Prostate adenocarcinoma (PC) and benign prostate hyperplasia (BPH) are age
      related diseases. The augmented oxidative stress is suggested to play an
      important role in the pathogenesis of both mentioned prostate disorders. In the
      presented study the antioxidant defense system in PC and BPH patients has been
      evaluated. The study was carried out on 30 PC patients (age 61+/-8 years) and 30
      BPH patients (age 63+/-8 years). The control group consisted of 25 healthy men
      (age 61+/-14 years). The reduced glutathione (GSH) concentrations in the
      erythrocytes and the activities of plasma superoxide dismutase (EC-SOD), plasma
      glutathione peroxidase (GPx-3), erythrocyte glutathione peroxidase (GPx-1) and
      erythrocyte glutathione S-transferase (GST) were measured in the examined groups.
      GSH concentrations in the erythrocytes and plasma GPx-3 activities in the PC
      group (2.31+/-0.27 mmol/l and 186.2+/-39 U/l, respectively) were significantly
      lower (P<0.05) as compared with the control group (2.52+/-0.24 and 211.8+/-26,
      respectively) and the BPH group (2.45+/-0.27 and 206.6+/-48, respectively).
      Erythrocyte GPx-1 activities in the BPH patients (14.76+/-3.5 U/g Hb) were
      statistically decreased (P<0.05) than in the healthy people (16.94+/-3.7) and in
      the PC patients (16.82+/-3.7). There were no significant differences in the
      activities of GST and EC-SOD between the PC group (2.72+/-1.34 nmol CDNB-GSH/mg
      Hb/min and 19.33+/-4.4 U/ml, respectively), the BPH group (2.53+/-1.00 and
      19.22+/-4.8, respectively) and the controls (2.88+/-0.82 and 19.40+/-4.1,
      respectively). These results indicate that antioxidant defense system is
      decreased in the elderly patients with PC and BPH. The differences in the
      antioxidative system between examined groups of patients may suggest the
      different etiologies of both diseases. KEYWORDS: antioxidative enzymes,
      antioxidant defense system, glutathione, benign prostate hyperplasia, prostate
      adenocarcinoma.

PMID- 25563376
TI  - Serum CYFRA21-1 as an effective tumor biomarker for patients with nasopharyngeal
      carcinoma.
AB  - We investigated if the serum cytokeratin 19 fragment 21.1 (CYFRA21-1) level was
      elevated in nasopharyngeal carcinoma (NPC) and can function as a biomarker for
      detection and monitoring of NPC. Three hundred and one study subjects were
      divided into two groups: the NPC group (n=126) and healthy control group (n=175).
      Serum CYFRA21-1 levels were measured before and after treatment using a
      chemiluminescent immunoassay, and its association with tumor stage and the
      clinical objective responses were analyzed. Receiver operating characteristic
      (ROC) curve analysis was performed to discriminate patients with NPC from the
      healthy controls. The pretreatment serum CYFRA21-1 level was significantly
      elevated in patients with NPC compared with the healthy controls (5.07+/-1.98
      ng/ml vs 2.36+/-1.21 ng/ml, p<0.001), and it declined significantly after the
      entire treatment (2.14+/-0.72 ng/ml, p<0.001). The serum CYFRA21-1 level of
      patients with a classification of T3-4 was significantly higher than that of
      those with class T1-2 (5.64+/-2.23 ng/ml vs 4.62+/-1.64 ng/ml, p=0.006), and that
      of patients with clinical stage III-IV was higher than clinical stage I-II
      (5.31+/-2.02 vs 4.04+/-1.37 ng/ml, p=0.003). The AUC, sensitivity and specificity
      of elevated serum CYFRA21-1 in patients with NPC was 0.91, 0.83 and 0.89
      respectively. In conclusion, the serum CYFRA21-1 level could be a reliable and
      effective biomarker for the detection and monitoring of NPC tumor progression.
      KEYWORDS: nasopharyngeal carcinoma, CYFRA21-1, tumor biomarker, receiver
      operating characteristic curve.

PMID- 25563377
TI  - Molecular cytogenetic analyses of hTERC (3q26) and MYC (8q24) genes
      amplifications in correlation with oncogenic human papillomavirus infection in
      Czech patients with cervical intraepithelial neoplasia and cervical carcinomas.
AB  - It is known that cervical cancer develop from precancerous intraepithelial
      neoplasia (CIN) which is characterized by series of genetic abnormalities. The
      progression of CIN to cervical carcinoma has been associated especially with the
      genomic integration of oncogenic human papilloma virus (HPV) and gain of the
      human telomerase RNA gene hTERC (3q26) and MYC (8q24). In this study, cytology
      specimens of cervical intraepithelial neoplasia and cervical carcinoma from 74
      Czech women were analyzed using the triple-color Cervical FISH Probe Kit designed
      for identification of HPV infected cells and copy number aberration of the hTERC
      and MYC genes. HPV-positivity exhibited 70% of patients with premalignant lesions
      (CIN I - CIN III, carcinoma in situ), chromosomal changes were found in 53.3% of
      cases - MYC amplification had 33.3% of women with CIN I - CIN III and 50% with
      carcinoma in situ. Amplification of hTERC was detected in 16.7% of patient with
      CIN I, in 50% with CIN II, in 58.3% with CIN III and in 66.7% with carcinoma in
      situ. Based on HPV-positivity and the occurrence of chromosomal aberrations,
      patients were divided into high-, intermediate- and low-risk group. Among women
      with cervical carcinomas, HPV infection was detected in 90.1% of specimens and
      chromosomal aberrations were found in 87.5% of samples. Amplification of MYC gene
      was detected in 25% and hTERC gene in 62.5% of patients. According to the
      histopathological grade of tumors, MYC gene amplification occurred more
      frequently in specimens of spinocellular carcinoma than adenocarcinoma (p=0.029).
      We found no association between the frequency of cytogenetic lesions and the
      incidence of lymphangiogenesis or lymph node metastases in cervical carcinoma
      patients. Simultaneous hTERC and MYC genes amplification was significantly more
      frequent in samples of cervical carcinomas than in premalignant lesions
      (p=0.008).In a cohort of 26 patients with cervical carcinoma we used oligo-based
      GGH+SNP microarray technique for the high resolution mapping of copy number
      changes of hTERC and MYC genes. We found that recurrent gain of genetic material
      in chromosome 3q26 area carrying hTERC gene of size 43.6 Mb between 3q25.1-3qter
      and duplication of 3q were the most common genomic identifications of amplified
      gene. In MYC locus array-CGH profiling identified duplication of 8q and trisomy 8
      as frequent genomic changes.Our work confirmed that in cervical carcinoma gains
      of hTERC and MYC genes are specific genomic changes associated with developing of
      malignant phenotype. We also showed that in premalignant stages HPV-FISH assay
      can be used as an effective diagnostic procedure to identify patients carrying
      highly risking HPV infection and chromosomal aberrations associated with this
      malignancy. KEYWORDS: cervical cancer, cervical dysplasia, HPV infection, hTERC
      amplification, MYC amplification, FISH, array-CGH.

PMID- 25563378
TI  - Allogeneic stem cell transplantation can improve outcome of AML patients without
      complete cytogenetic response after induction and consolidation treatment.
AB  - Our retrospective analysis was performed on 376 consecutive patients diagnosed
      with AML. A total of 256 (68%) were treated with standard "7+3" induction and
      high-dose cytarabine and mitoxantrone containing "4+3"
      consolidation/intensification regimens. Our study focused on patients with
      presumably very poor prognosis - patients, who did not achieve complete
      cytogenetic remission (CRc). Twenty-five AML patients without CRc were further
      analysed for clinical and laboratory parameters. Firstly, the subgroups with or
      without morphologic CR were compared. Similar cytogenetic abnormalities were
      observed in both with myelodysplasia related changes being the most common.
      Complex karyotype with deletion of 5q constituted approximately a third of all
      karyotypes in both subgroups. There were 1 patient with intermediate risk
      cytogenetics in the subgroup without morphologic CR and 5 patients in the
      subgroup with morphologic CR. Interestingly, in 4/25 patients subclones were
      diminished by the chemotherapy treatment, however cytogenetically less advanced
      clones proliferated. Secondly, transplanted or nontransplanted patients were
      analysed. Allogeneic stem cell transplantation (allo-SCT) was found to be the
      only curative treatment for patients without CRc after 7+3 and 4+3 regimens. In
      our cohort, 40% of the patients, who underwent allo-SCT, are alive. Importantly,
      67% of the patients, who died after allo-SCT, died of causes unrelated to
      progression of AML. Nonrelapse mortality is therefore one of the fields where
      survival could be further improved. KEYWORDS: acute myeloid leukaemia, complete
      cytogenetic remission, cytogenetic abnormalities, stem cell transplantation,
      nonrelapse mortality.

PMID- 25563379
TI  - Acute promyelocytic leukemia successfully treated also in elderly patients with
      significant comorbidities: a 20-year single-center experienc.
AB  - Acute promyelocytic leukemia is a unique entity among acute leukemias.
      Introduction of all-trans retinoic acid and, subsequently, arsenic trioxide in
      its treatment has markedly improved treatment outcomes for this once frequently
      fatal disease. Improved outcomes have also been observed in elderly patients,
      including those in whom standard intensive therapy is contraindicated because of
      comorbidities.In our center, a total of 60 APL patients were treated in 1993
      2013, of whom 9 were aged 60 or more years. Although most of them had significant
      comorbidities at the time of diagnosis, eight achieved complete remission. At the
      time of the analysis, six patients were alive and in long-term remission; two
      patients died of causes other than APL. The median follow-up was 59
      months.Included is case report of a patient with a high comorbidity score whose
      treatment was markedly reduced and individualized.Our experience shows that, in
      APL patients a curative approach is generally tolerated and should always be
      attempted regardless of age and comorbidities. KEYWORDS: APL - elderly patients -
      comorbidity.

PMID- 25563380
TI  - GROalpha expression and its prognostic implications in laryngeal squamous cell
      carcinoma.
AB  - The growth-regulated oncogene alpha (GROalpha) , which is also designated as CXC
      chemokine ligand 1 (CXCL1), was first identified as an autocrine growth factor in
      human malignant melanoma. It is involved in tumor development and invasion, and
      is highly expressed in various human cancers. However, little is known about the
      association between GROalpha expression and the clinical attributes of laryngeal
      squamous cell carcinoma (LSCC). One-step quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) and immunohistochemical staining of tissue
      microarrays were employed to evaluate the relationship between GROalpha
      expression and LSCC clinicopathological attributes. GROalpha mRNA and protein
      expression levels were significantly greater in LSCC than in non-cancerous tumor
      adjacent tissues. GROalpha protein expression in LSCC was also significantly
      associated with TNM stage, lymph node metastasis, and histopathological grade.
      Kaplan-Meier and Cox multi-factor analyses suggested that increased GROalpha
      expression and positive lymph node metastasis were significantly associated with
      the poor survival of LSCC patients. These data indicate that GROalpha may be a
      novel prognostic marker of LSCC. KEYWORDS:
      GROalpha,LSCC,qPCR,immunohistochemistry, prognosis.

PMID- 25563382
TI  - Factors Associated With Being Pleased With a Female Partner Pregnancy Among
      Sexually Active U.S. Adolescent Males.
AB  - Adolescent pregnancy remains a major U.S. public health problem. Little is known
      about pregnancy attitudes in U.S. adolescent males. The study objective was to
      identify factors from different domains that are associated with sexually active
      U.S. adolescent males who would be pleased with a female partner pregnancy
      (hereafter known as pleased with a pregnancy). The National Survey of Family
      Growth is a nationally representative survey of those 15 to 44 years old.
      Bivariate and multivariable analyses were performed of the 2002 and 2006-2010
      cycles to examine factors associated with being pleased with a pregnancy among
      sexually active U.S. males. Among the 1,445 sexually active U.S. adolescent males
      surveyed, 25% would be pleased with a pregnancy. In bivariate analyses, ever
      being suspended from school, having sporadic health insurance, age, and ever HIV
      tested were significantly associated with being pleased with a pregnancy. In
      final multivariable analyses, sporadic insurance was associated with almost
      triple the odds, and being older and ever HIV tested with double the odds of
      being pleased with a pregnancy. Higher educational attainment for both adolescent
      males and adolescent males' fathers was associated with reduced odds of a being
      pleased with a pregnancy. One quarter of sexually active U.S. adolescent males
      would be pleased with a pregnancy. Adolescent males who have been sporadically
      insured, are older, and ever HIV tested have higher odds of being pleased with a
      pregnancy. Targeting these adolescent males for more focused pregnancy-prevention
      counseling may prove useful in reducing adolescent pregnancy rates.

PMID- 25563381
TI  - Digital Solutions for Informed Decision Making: An Academic-Community Partnership
      for the Development of a Prostate Cancer Decision Aid for African American Men.
AB  - African American (AA) men are significantly more likely to die of prostate cancer
      (PrCA) than other racial groups, and there is a critical need to identify
      strategies for providing information about PrCA screening and the importance of
      informed decision making (IDM). To assess whether a computer-based IDM
      intervention for PrCA screening would be appropriate for AA men, this formative
      evaluation study examined their (1) PrCA risk and screening knowledge; (2)
      decision-making processes for PrCA screening; (3) usage of, attitudes toward, and
      access to interactive communication technologies (ICTs); and (4) perceptions
      regarding a future, novel, computer-based PrCA education intervention. A
      purposive convenience sample of 39 AA men aged 37 to 66 years in the Southeastern
      United States was recruited through faith-based organizations to participate in
      one of six 90-minute focus groups and complete a 45-item descriptive survey.
      Participants were generally knowledgeable about PrCA. However, few engaged in IDM
      with their doctor and few were informed about the associated risks and
      uncertainties of PrCA screening. Most participants used ICTs on a daily basis for
      various purposes including health information seeking. Most participants were
      open to a novel, computer-based intervention if the system was easy to use and
      its animated avatars were culturally appropriate. Because study participants had
      low exposure to IDM for PrCA, but frequently used ICTs, IDM interventions using
      ICTs (e.g., computers) hold promise for AA men and should be explored for
      feasibility and effectiveness. These interventions should aim to increase PrCA
      screening knowledge and stress the importance of participating in IDM with
      doctors.

PMID- 25563384
TI  - Consultation for Small-Sized Penis in the Egyptian Males: A Case Control Study.
AB  - This study aimed to report penile dimensions in adult Egyptian males consulting
      for small-sized penis (SSP) and describe their demographics and andrological
      profile. A case control study was designed through retrospective data analysis of
      patients (n = 239) seeking advice for SSP and a control group (n = 59). This
      included sociodemographics, other andrological complaints, and penile dimensions
      (pendulous length [PL], penopubic or total length [TL], and circumference [CF])
      at flaccid and erect states and the size of the prepubic fatty pad. The results
      reported that most patients were single, students, and smokers and had not
      completed a university education. Several patients reported falsely premature
      ejaculation (PE), penile curvature (PC), and small-sized testes. Most penile
      dimensions of the patients (mean, cm) were significantly lower than those of the
      controls, whether in flaccid (PL: 7.4 vs. 8.05, p = .008; CF: 8.7 vs. 8.98, p =
      .026) or erect state (PL: 11.8 vs. 13, p = .000; TL: 14.2 vs. 15, p = .000; CF:
      11.3 vs. 11.8, p = .003). However, no patient presented with a pendulous penile
      length <4 cm in flaccid or <7 cm in erect state. In conclusion, Egyptian men
      consulting for SSP did not have true small organs, but their penile dimensions
      were slightly smaller than those of men without such complaint. The proper sexual
      education program is highly advisable in these situations to avoid the myths and
      misconceptions about sexuality.

PMID- 25563383
TI  - A Synthesis of 20 Years of Research on Sexual Risk Taking Among Asian/Pacific
      Islander Men Who Have Sex With Men in Western Countries.
AB  - Over the past two decades, there has emerged a body of literature documenting a
      number of risk factors associated with Asian/Pacific Islander men who have sex
      with men's unsafe sexual behaviors. This study aims to systematically review
      existing empirical studies and synthesize research results into a social
      ecological framework using a mixed research synthesis. Empirical research
      articles published in peer-reviewed journals between January 1990 and June 2013
      were identified in six databases, including PubMed, Ovid MEDLINE, PsycINFO,
      Social Work Abstract, CINAL, and Web of Knowledge. Both quantitative and
      qualitative studies were included. Two analysts independently reviewed the
      articles, and findings were organized on a social-ecological framework. Twenty
      two articles were included in the analysis; among these 13 were quantitative, 8
      were qualitative, and 1 was mixed-methods research. Results indicated that
      demographic characteristics, psychological resources, behavioral patterns,
      relationships with family and friends, dynamics with romantic or sexual partners,
      community involvement, culture, discrimination, and institutional factors were
      related to unprotected anal intercourse. This article presents a critique of this
      literature and discusses implications for future research with this population.
      It concludes with prevention/intervention initiatives based on review findings.

PMID- 25563385
TI  - An immunohistochemical study of CD83- and CD1a-positive dendritic cells in the
      decidua of women with recurrent spontaneous abortion.
AB  - BACKGROUND: There are more and more women with recurrent spontaneous abortion
      (RSA). The mechanism of RSA is still unclear. Immunological factors have been
      postulated to play a role in the etiology of RSA. Dendritic cells (DCs) are the
      most potent antigen-presenting cells in the immune system, and the decidual DCs
      may take part in the occurrence of RSA. The difference in maturity status of
      decidual DCs among women with RSA and women with normal pregnancies is worthy of
      studying for its application to prevention and therapy. METHODS: The EnVision two
      step immunohistochemical staining technique was used to detect the expression of
      CD83 and CD1a in the decidua of women with RSA (30 cases) and normal pregnancies
      (30 cases). The maturity status, distribution and quantity of DCs in the two
      groups were observed. Observation of the staining and cell counting were done
      using microscope within 30 randomly selected high-power fields (HPF, 40 * 10).
      All data analyses were conducted with SPSS 17.0 and the statistical significance
      was set at P <0.05. RESULTS: The decidua from the two groups contained DCs that
      stained with the anti-CD83 and anti-CD1a antibody. Most of the decidual
      CD83(+)DCs from two groups were located in the stroma. There were more CD83(+)DCs
      clustered with other DCs in the stroma from women with RSA than normal
      pregnancies. Most of the CD1a(+)DCs in the decidua from the two groups are
      located close to maternal glandular epithelium. No difference in the location of
      CD1a(+)DCs was found in the decidua between two groups. The number of decidual
      CD83(+)DCs was statistically significantly higher in RSA women than in normal
      early pregnant women (14.20 +/- 13.34/30 HPF versus 4.77 +/- 2.64/30 HPF; t =
      3.800, P = 0.001). The number of CD1a(+)DCs in the decidua was statistically
      significantly lower in RSA women compared with normal early pregnant women (3.97
      +/- 3.75/30 HPF versus 7.60 +/- 6.08/30 HPF; t = 2.786, P = 0.008). CONCLUSIONS:
      These findings suggest that the increase in the number of mature DCs and the
      decrease in the quantity of immature DCs in the decidua may be related to RSA.
      The maturation of decidual DCs may play an important role in the pathogenesis of
      RSA.

PMID- 25563386
TI  - Maternal resources and household food security: evidence from Nicaragua.
AB  - OBJECTIVE: Women (especially mothers) are theorized as critical to reducing
      household food insecurity through their work and caregiver roles. The present
      study tests these assumptions, assessing how maternal economic and social
      resources are associated with food insecurity in households with young children.
      DESIGN: Data from a population-based sample of households was collected in Leon,
      Nicaragua (n 443). Data include a newly validated measure of household food
      insecurity (ELCSA), maternal resource measures, and household economic status and
      demographics. Regression analysis tests the statistical associations (P<0.05) of
      maternal resources with household, adult-specific and child-specific food
      insecurity. SETTING: Municipality of Leon, Nicaragua. SUBJECTS: Households with
      children aged 3-11 years in rural and urban Leon. RESULTS: Only 25% of households
      with young children were food secure, with 50% mildly food insecure and 25%
      moderately/severely food insecure. When mothers contributed substantially to
      household income, the odds of moderate/severe household food insecurity were 34%
      lower than when their spouse/partner was the main provider. The odds of food
      insecurity were 60% lower when mothers managed household money, 48% lower when
      mothers had a secondary (v. primary) education, 65% higher among single mothers
      and 16% lower with each indicator of social support. Results were similar for
      adult- and child-specific food insecurity. CONCLUSIONS: This research provides
      new evidence that maternal economic and social resources are important for
      reducing household food insecurity and adult- and child-specific food insecurity.
      Women's social status, social support and access to economic resources need to be
      enhanced as a part of policies aimed to reduce food insecurity in high-poverty
      settings.

PMID- 25563387
TI  - Coumarin 545: an emission reference dye with a record-low temperature coefficient
      for ratiometric fluorescence based temperature measurements.
AB  - The emission intensities of coumarin 545 solution exhibit a low temperature
      dependence, with a record-low temperature coefficient of only ~0.025% per 
      degrees C. This monomer-aggregate coupled fluorescence system can be used for
      ratiometric temperature measurements with high spatial and temporal resolutions;
      three different working modes have been demonstrated. 

PMID- 25563388
TI  - New insights into the nitroaromatics-detection mechanism of the luminescent metal
      organic framework sensor.
AB  - Luminescent metal-organic frameworks (LMOFs) have emerged as a group of new and
      very promising optic sensors in the detection of explosives. However, fundamental
      understanding of the sensing mechanisms on these materials is still immature and
      detailed investigations are needed. In this contribution, density functional
      theory (DFT) and time-dependent density functional theory (TD-DFT) are applied to
      reveal the underlying principles for the sensing mechanism by comprehensively
      studying the analyte-sensor interactions. Three molecules namely nitrobenzene,
      benzene and acetone are chosen as analytes while a newly reported explosives
      detecting LMOF [Zn(2)(L)(bipy)(H(2)O)(2)].(H(2)O)(3)(DMF)(2) is chosen as the
      sensor. Roles of two fundamental weak interactions namely hydrogen bonding
      interaction and pi-pi stacking interaction are clarified for the first time. By
      studying both the periodic crystal models and cluster models we obtained an in
      depth understanding of the detecting mechanism from the view of electronic
      coupling. We find that intermolecular electron transfer is the inducement for the
      luminescence quenching detection of explosives. A brand new pathway for this
      electron transfer process is proposed for the first time. Most significantly, we
      discover that the hydrogen bond shows multi-functions during the detecting
      processes which, on the one hand, serves as the electron transfer bridge, and on
      the other hand, reinforces the pi-pi stacking. This cooperative effect of the two
      weak forces inside MOFs is investigated for the first time, which not only
      provides valuable insights into the understanding of the analyte-sensor
      interactions inside the sensors but also offers useful guidance in the design of
      MOF sensors to achieve high sensitivity.

PMID- 25563389
TI  - Spontaneous doping of two-dimensional NaCl films with Cr atoms: aggregation and
      electronic structure.
AB  - Scanning tunneling microscopy (STM) experiments combined with density functional
      theory (DFT) calculations reveal that deposited Cr atoms replace either Na or Cl
      ions, forming substituting dopants in ultrathin NaCl/Au(111) films. The Cr
      dopants exchange electrons with the support thus changing the electronic
      properties of the film and in particular the work function. The Cr atoms
      spontaneously aggregate near the edges of the bilayer (2L) NaCl islands, forming
      a new phase in the insulator with a remarkably dense population of Cr dopants.
      The spectra of differential conductance yield evidence that, compared to the
      undoped or Cr-poor 2L NaCl films on Au(111), the Cr-rich region shows different
      interface states, shifted image-potential states, and a reduced work function.
      This demonstrates the potential of doping ultrathin films to modify their
      adsorption properties in a desired manner. 

PMID- 25563390
TI  - Maximising response from GPs to questionnaire surveys: do length or incentives
      make a difference?
AB  - BACKGROUND: General Practitioners (GPs) respond poorly to postal surveys.
      Consequently there is potential for reduced data quality and bias in the
      findings. In general population surveys, response to postal questionnaires may be
      improved by reducing their length and offering incentives. The aim of this study
      was to investigate whether questionnaire length and/or the offer of an incentive
      improves the response of GPs to a postal questionnaire survey. METHODS: A postal
      questionnaire survey was sent to 800 UK GPs randomly selected from Binley's
      database; a database containing contact details of professionals working in UK
      general practices. The random sample of GPs was assigned to one of four groups of
      200, each receiving a different questionnaire, either a standard (eight sides of
      A4) or an abbreviated (four sides of A4) questionnaire, with or without the offer
      of an incentive (a prize draw entry for a L100 voucher) for completion. The
      effects of questionnaire length and offer of incentive on response were
      calculated. RESULTS: Of 800 mailed questionnaires, 19 GPs did not meet inclusion
      criteria and 172 (adjusted response 22.0%) completed questionnaires were
      received. Among the four groups, response ranged from 20.1% (standard
      questionnaire with no incentive and abbreviated questionnaire with incentive)
      through 21.8% (standard questionnaire with incentive), to 26.0% (abbreviated
      questionnaire with no incentive). There were no significant differences in
      response between the four groups (p = 0.447), between the groups receiving the
      standard versus the abbreviated questionnaire (% difference -2.1% (95% confidence
      interval (CI) -7.9, 3.7)) or the groups offered an incentive versus no incentive
      (% difference -2.1% (95% CI -7.9, 3.7). CONCLUSIONS: Strategies known to improve
      response to postal questionnaire surveys in the general population do not
      significantly improve the response to postal questionnaire surveys among GPs.
      Further refinements to these strategies, or more novel strategies, aimed at
      increasing response specifically among GPs need to be identified in order to
      maximise data quality and generalisability of research results.

PMID- 25563391
TI  - Asymmetric Michael addition of alpha-fluoro-alpha-nitro esters to nitroolefins:
      towards synthesis of alpha-fluoro-alpha-substituted amino acids.
AB  - alpha-Fluoro-alpha-nitro esters were used as reaction partners in Michael
      addition to nitroalkenes, and the products were obtained in excellent chemical
      yields and with high enantioselectivities. Moreover, alpha-fluoro-alpha-amino
      ester with a quaternary alpha-carbon was prepared for the first time. 

PMID- 25563392
TI  - [Usefulness of procalcitonin and C-reactive protein to predict bacteremia in the
      elderly patient or with immunosuppression].

PMID- 25563394
TI  - Spectrally resolved confocal microscopy using lanthanide centred near-IR
      emission.
AB  - The narrow, near infrared (NIR) emission from lanthanide ions has attracted great
      interest, particularly with regard to developing tools for bioimaging, where the
      long lifetimes of lanthanide excited states can be exploited to address problems
      arising from autofluorescence and sample transparency. Despite the promise of
      lanthanide-based probes for near-IR imaging, few reports on their use are present
      in the literature. Here, we demonstrate that images can be recorded by monitoring
      NIR emission from lanthanide complexes using detectors, optical elements and a
      microscope that were primarily designed for the visible part of the spectrum. 

PMID- 25563393
TI  - Executive summary of the diagnosis and antimicrobial treatment of invasive
      infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the
      Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).
AB  - The spread of multidrug-resistant Enterobacteriaceae related to the production of
      extended-spectrum beta-lactamases (ESBL) and carbapenemases is a serious public
      health problem worldwide. Microbiological diagnosis and therapy of these
      infections are challenging and controversial. After the selection of clinically
      relevant questions, this document provides evidence-based recommendations for the
      use of microbiological techniques for the detection of ESBL- and carbapenemase
      producing Enterobacteriaceae, and for antibiotic therapy for invasive infections
      caused by these organisms. The absence of randomized-controlled trials is
      noteworthy, thus recommendations are mainly based on observational studies, that
      have important methodological limitations, pharmacokinetic and pharmacodynamics
      models, and data from animal studies. Additionally, areas for future research
      were identified.

PMID- 25563395
TI  - Hierarchical mesoporous yolk-shell structured carbonaceous nanospheres for high
      performance electrochemical capacitive energy storage.
AB  - Hierarchical mesoporous yolk-shell structured carbon nanospheres (YSCNs) with an
      ordered mesoporous carbon core and a microporous carbon shell show excellent
      electrochemical performance with a maximal specific capacitance of 159 F g(-1). 

PMID- 25563396
TI  - The chain conformation and relaxation dynamics of poly(acrylic acid)-graft
      poly(ethylene oxide)-graft-dodecyl in water: effect of side-chains and
      distribution of counterions.
AB  - We present a study on the dielectric behavior of an aqueous solution of an
      amphiphilic copolymer, poly(acrylic acid)-graft-poly(ethylene oxide)-graft
      dodecyl (PAA-g-PEO-g-dodecyl), in the frequency range of 40 Hz to 110 MHz at
      varying concentrations and temperatures. After eliminating the electrode
      polarization at low-frequency, three dielectric relaxation processes were
      observed at about 1.2 MHz, 150 kHz and 30 kHz, whose mechanisms were proved to
      originate from the fluctuations of free counterions, the fluctuation of condensed
      counterions, and the rotation of intramolecular aggregates, respectively. The
      concentration dependence of the dielectric increment Deltaepsilon and relaxation
      time tau for these three relaxations presents an abrupt change at 0.15 mg ml(-1),
      indicating that PAA-g-PEO-g-dodecyl molecules undergo a conformational transition
      from intramolecular aggregates to intermolecular aggregates. Moreover, both
      Deltaepsilon and tau show a clear transition at about 317 K, suggesting a partial
      collapse of the aggregates. The correlation length and the contour length of the
      PAA-g-PEO-g-dodecyl chain were estimated according to Ito's theory of counterion
      fluctuation. It was found that the hydrophobic/hydrophilic side-chains affected
      the microscopic conformation of PAA, and the hydrogen-bond interactions greatly
      influenced the conformation. Additionally, the activation energy of these three
      relaxations was calculated and the process of ionic conduction was studied and
      the results were used to discuss counterion distribution and ion conduction. 

PMID- 25563398
TI  - Online capillary solid-phase microextraction coupled liquid chromatography-mass
      spectrometry for analysis of chiral secondary alcohol products in yeast catalyzed
      stereoselective reduction cell culture.
AB  - An online solid-phase microextraction coupled liquid chromatography-electrospray
      ionization-ion trap mass spectrometry was developed for the analysis of trace R-
      and S-4-phenyl-2-butanol (R- and S-pbol) in salt rich cell culture of
      Saccharomyces cerevisiae catalyzed stereoselective reduction of 4-pheny-2
      butanone (pbone). A Supel-Q PLOT capillary column was used for the extraction and
      deionized distilled water was used as the extraction mobile phase. The extraction
      flow rate and extraction time were at 0.1 mL min(-1) and 0.95 min, respectively.
      The three target analytes, pbone, R-pbol, and S-4-pbol, were desorbed and eluted
      by the mobile phase of water/methanol/isopropanol (55/25/20, v/v/v) with a flow
      rate of 0.5 mL min(-1) and analyzed by a chiral column. The mass spectrometric
      detection of the three target analytes was in positive ion mode with the signal
      [M+Na](+). The matrix-matched external standard calibration curves with linear
      concentration range between 0 and 50 MUg mL(-1) were used for quantitative
      analysis. The linear regression correlation coefficients (r(2)) of the standard
      calibration curves were between 0.9950 and 0.9961. The yeast mediated reduction
      was performed with a recation culture of yeast incubation culture/glycerol
      (70/30, v/v) for 4 days. This biotransformation possessed 82.3% yield and 92.9% S
      enantomeric excess. The limit of detection (LOD)/limit of quantification (LOQ)
      for pbone, R-pbol, and S-pbol was 0.02/0.067, 0.01/0.033, and 0.01/0.033 MUg mL(
      1), respectively. The intra-day and inter-day precisions from repeated
      measurements were 10.8-21.1% and 11.6-18.7%, respectively. The analysis accuracy
      from spike recovery was 84-91%.

PMID- 25563397
TI  - Molecular analysis of the benthos microbial community in Zavarzin thermal spring
      (Uzon Caldera, Kamchatka, Russia).
AB  - BACKGROUND: Geothermal areas are of great interest for the study of microbial
      communities. The results of such investigations can be used in a variety of
      fields (ecology, microbiology, medicine) to answer fundamental questions, as well
      as those with practical benefits. Uzon caldera is located in the Uzon-Geyser
      depression that is situated in the centre of the Karym-Semyachin region of the
      East Kamchatka graben-synclinorium. The microbial communities of Zavarzin spring
      are well studied; however, its benthic microbial mat has not been previously
      described. RESULTS: Pyrosequencing of the V3 region of the 16S rRNA gene was used
      to study the benthic microbial community of the Zavarzin thermal spring (Uzon
      Caldera, Kamchatka). The community is dominated by bacteria (>95% of all
      sequences), including thermophilic, chemoorganotrophic Caldiserica (33.0%) and
      Dictyoglomi (24.8%). The benthic community and the previously examined planktonic
      community of Zavarzin spring have qualitatively similar, but quantitatively
      different, compositions. CONCLUSIONS: In this study, we performed a metagenomic
      analysis of the benthic microbial mat of Zavarzin spring. We compared this
      benthic community to microbial communities found in the water and of an integral
      probe consisting of water and bottom sediments. Various phylogenetic groups of
      microorganisms, including potentially new ones, represent the full-fledged
      trophic system of Zavarzin. A thorough geochemical study of the spring was
      performed.

PMID- 25563400
TI  - Ionic liquid-modulated preparation of hexagonal tungsten trioxide mesocrystals
      for lithium-ion batteries.
AB  - Hexagonal (h-WO3) mesocrystals with biconical morphology were prepared by a
      straightforward ionic liquid-assisted hydrothermal route and investigated as
      anodic materials for lithium-ion batteries. Compared to the alternatives, the
      biconical tungsten trioxide mesocrystal exhibited excellent lithium insertion
      with good cyclability and rate capability, making it a promising candidate as the
      anode material for high-performance lithium-ion batteries. 

PMID- 25563399
TI  - Prevalence and risk factors of hypertension among pre- and post-menopausal women:
      a cross-sectional study in a rural area of northeast China.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence and risk factors
      of hypertension in pre-menopausal women (Pre-MW) and post-menopausal women (Post
      MW) and determine whether years since menopause (YSM) is associated with
      hypertension. METHODS: A cross-sectional study was conducted with 6324 women over
      35 years of age (2616 Pre-MW and 3708 Post-MW). Questionnaires, measurements and
      blood biochemical indexes were collected. RESULTS: The overall prevalence of
      hypertension among women in rural northeast China was 48.8%, and it increased
      with age. Post-MW had a higher prevalence of hypertension than Pre-MW (62.4% vs.
      29.7%, P<0.01). After controlling for confounding variables, overweight (OR=1.97,
      95% CI: 1.72-2.25), obesity (OR=2.97, 95% CI: 2.30-3.84), diabetes mellitus
      (OR=2.13, 95% CI: 1.73-2.62), high triglycerides (OR=1.41, 95% CI: 1.20-1.65),
      and history of cardiovascular diseases in first-degree relatives (OR=1.60, 95%
      CI: 1.42-1.81) were associated with hypertension in all participants. However,
      abdominal obesity (OR=1.29, 95% CI: 1.05-1.58) was associated with higher odds
      among Post-MW only. Hypertension was associated with being postmenopausal
      (OR=1.22; 95% CI: 1.03-1.46), and the risk of hypertension reached a peak level
      in the <5-year group (OR=1.29; 95% CI, 1.07-1.57). CONCLUSIONS: Postmenopausal
      status was an independent risk factor for hypertension. The risk of hypertension
      was highest in Post-MW with <5 YSM and then decreased. Other risk factors of
      hypertension were body mass index (BMI), abdominal obesity, a family history of
      cardiovascular disease among first-degree relatives, a personal history of
      diabetes, and high TG.

PMID- 25563401
TI  - Hearing rehabilitation with a binaural cochlear implant in a patient with Erdheim
      Chester disease.
AB  - OBJECTIVE AND IMPORTANCE: Erdheim-Chester disease (ECD) is a rare non-Langerhans
      form of histiocytosis. This paper reports an exceptional case of bilateral neural
      involvement, responsible for profound hearing loss. Bilateral cochlear
      implantation was performed. CLINICAL PRESENTATION: We present a 57-year-old man
      affected by ECD with profound bilateral hearing loss. INTERVENTION: The patient
      underwent cochlear implantation with a binaural Digisonic((r)) cochlear implant,
      7 years after the initial diagnosis. RESULTS: Speech intelligibility rose to a
      plateau after about 6 months of cochlear implant use. The average outcome of
      speech intelligibility over time was 55% for dissyllabic words without lip
      reading, and 70% for sentences. Perception score decreased before the patient
      died from ECD. CONCLUSION: A description of the ECD and its otological
      manifestations is presented. This paper reports the effective hearing
      rehabilitation of profound bilateral hearing loss by the means of a binaural
      Digisonic((r)) cochlear implant.

PMID- 25563402
TI  - Two-dimensional photonic crystals for sensitive microscale chemical and
      biochemical sensing.
AB  - Photonic crystals - optical devices able to respond to changes in the refractive
      index of a small volume of space - are an emerging class of label-free chemical-
      and bio-sensors. This review focuses on one class of photonic crystal, in which
      light is confined to a patterned planar material layer of sub-wavelength
      thickness. These devices are small (on the order of tens to hundreds of microns
      square), suitable for incorporation into lab-on-a-chip systems, and in theory can
      provide exceptional sensitivity. We introduce the defining characteristics and
      basic operation of two-dimensional photonic crystal sensors, describe variations
      of their basic design geometry, and summarize reported detection results from
      chemical and biological sensing experiments. 

PMID- 25563405
TI  - Commentary: Sustained advocacy produces success in the Philippines.

PMID- 25563404
TI  - Barriers, motivators and enablers for dispensing multifocal contact lenses in
      Mumbai, India.
AB  - PURPOSE: To understand the potential barriers, motivators and enablers in
      dispensing multifocal contact lenses (MFCL). METHOD: Two focus group discussions
      were conducted to design questionnaires regarding the prescribing habits for
      multifocal contact lenses (MFCL). Questions on potential barriers and motivators
      were included. The questionnaires were distributed among 133 eye care
      practitioners across Mumbai, India. Practitioners fitting one or less patient per
      month with MFCL completed the survey describing potential barriers, while those
      who prescribed more MFCL's per month completed the survey describing enablers and
      motivators. RESULTS: Responses from 102 practitioners were received. Most common
      potential barriers in prescribing MFCL were increased chair time (75%), lack of
      readily available trials (69%) and limitation in power range (63%). Lack of
      awareness among patients (90%) was the most common barrier from patients'
      outlook. Professional satisfaction (88%) and better business proposition (82%)
      were observed as main motivators while availability of the trials (84%) and
      correct patient selection (82%) were the major enablers. Graduate Optometrists
      felt dispensing MFCL did not offer a good business proposition (p=0.02).
      Experienced practitioners were observed to be least motivated (p=0.01) and
      believed that their patients found these lenses expensive (p=0.02). CONCLUSION:
      To enhance the MFCL practice, barriers like lack of awareness and limitations in
      power range must be addressed. Trial lens availability may motivate practitioners
      to prescribe MFCL. Further probing is required to understand lack of motivation
      among experienced practitioners.

PMID- 25563403
TI  - Influenza A (H1N1) virus infection triggers severe pulmonary inflammation in
      lupus-prone mice following viral clearance.
AB  - Each year, up to one fifth of the United States population is infected with
      influenza virus. Although mortality rates are low, hundreds of thousands are
      hospitalized each year in the United States. Specific high risk groups, such as
      those with suppressed or dysregulated immune systems, are at greater danger for
      influenza complications. Respiratory infections are a common cause of
      hospitalizations and early mortality in patients with systemic lupus
      erythematosus (SLE); however, whether this increased infection risk is a
      consequence of the underlying dysregulated immune background and/or
      immunosuppressing drugs is unknown. To evaluate the influenza immune response in
      the context of lupus, as well as assess the effect of infection on autoimmune
      disease in a controlled setting, we infected lupus-prone MRL/MpJ-Fas(lpr) mice
      with influenza virus A PR/8/34 H1N1. Interestingly, we found that Fas(lpr) mice
      generated more influenza A virus specific T cells with less neutrophil
      accumulation in the lung during acute infection. Moreover, Fas(lpr) mice produced
      fewer flu-specific IgG and IgM antibodies, but effectively cleared the virus.
      Further, increased extrinsic apoptosis during influenza infection led to a delay
      in autoimmune disease pathology with decreased severity of splenomegaly and
      kidney disease. Following primary influenza A infection, Fas(lpr) mice had severe
      complications during the contraction and resolution phase with widespread severe
      pulmonary inflammation. Our findings suggest that influenza infection may not
      exacerbate autoimmune pathology in mice during acute infection as a direct result
      of virus induced apoptosis. Additionally, autoimmunity drives an enhanced antigen
      specific T cell response to clear the virus, but persisting pulmonary
      inflammation following viral clearance may cause complications in this lupus
      animal model. 

PMID- 25563407
TI  - The relevance of the first ribs of the El Sidron site (Asturias, Spain) for the
      understanding of the Neandertal thorax.
AB  - Reconstructing the morphology of the Neanderthal rib cage not only provides
      information about the general evolution of human body shape but also aids
      understanding of functional anatomy and energetics. Despite this paleobiological
      importance there is still debate about the nature and extent of variations in the
      size and shape of the Neandertal thorax. The El Sidron Neandertals can be used to
      contribute to this debate, providing new costal remains ranging from fully
      preserved and undistorted ribs to highly fragmented elements. Six first ribs are
      particularly well preserved and offer the opportunity to analyze thorax
      morphology in Neandertals. The aims of this paper are to present this new
      material, to compare the ontogenetic trajectories of the first ribs between
      Neandertals and modern humans, and, using geometric morphometrics, to test the
      hypothesis of morphological integration between the first rib and overall thorax
      morphology. The first ribs of the El Sidron adult Neandertals are smaller in
      centroid size and tend to be less curved when compared with those of modern
      humans, but are similar to Kebara 2. Our results further show that the
      straightening of the first ribs is significantly correlated with a straightening
      of the ribs of the upper thorax (R = 0.66; p < 0.0001) in modern humans,
      suggesting modularity in the upper and lower thorax units as reported in other
      hominins. It also supports the hypothesis that the upper thorax of Neandertals
      differs in shape from modern humans with more anteriorly projecting upper ribs
      during inspiration. These differences could have biomechanical consequences and
      account for stronger muscle attachments in Neandertals. Different upper thorax
      shape would also imply a different spatial arrangement of the shoulder girdle and
      articulation with the humerus (torsion) and its connection to the upper thorax.
      Future research should address these inferences in the context of Neandertal
      overall body morphology. 

PMID- 25563408
TI  - New actualistic data on the ecology and energetics of hominin scavenging
      opportunities.
AB  - For decades, the 'hunting-scavenging debate' has been an important research focus
      in Plio-Pleistocene hominin behavioral ecology. Here I present new data on
      potential scavenging opportunities from fresh carnivore kills on a conservancy in
      central Kenya. This ecosystem is dominated by felids (mainly lions) and has a
      different carnivore guild than in many earlier studies of scavenging
      opportunities that took place in areas such as Ngorongoro and Serengeti in
      Tanzania and Maasai Mara in Kenya, where lions face high levels of inter-specific
      competition from bone-crunching hyenas. I found that while scavenging
      opportunities vary among carcasses, most carcasses retained some scavengeable
      resources. Excluding within-bone resources, even the scavengeable meat on
      'defleshed' larger sized prey carcasses is usually substantial enough to meet the
      total daily caloric requirements of at least one adult male Homo erectus
      individual. I argue, as others have before me, that scavenging opportunities in a
      particular ecosystem will vary in part due to carnivore taxon, density and guild
      composition; prey size, biomass and community structure; and habitat (e.g.,
      vegetation, physiography). We should expect variability in scavenging
      opportunities in different locales and should focus our research efforts on
      identifying which variables condition these differences in order to make our
      findings applicable to the diversity of ecological settings characterizing the
      past. 

PMID- 25563409
TI  - Insights into hominin phenotypic and dietary evolution from ancient DNA sequence
      data.
AB  - Nuclear genome sequence data from Neandertals, Denisovans, and archaic
      anatomically modern humans can be used to complement our understanding of hominin
      evolutionary biology and ecology through i) direct inference of archaic hominin
      phenotypes, ii) indirect inference of those phenotypes by identifying the effects
      of previously-introgressed alleles still present among modern humans, or iii)
      determining the evolutionary timing of relevant hominin-specific genetic changes.
      Here we review and reanalyze published Neandertal and Denisovan genome sequence
      data to illustrate an example of the third approach. Specifically, we infer the
      timing of five human gene presence/absence changes that may be related to
      particular hominin-specific dietary changes and discuss these results in the
      context of our broader reconstructions of hominin evolutionary ecology. We show
      that pseudogenizing (gene loss) mutations in the TAS2R62 and TAS2R64 bitter taste
      receptor genes and the MYH16 masticatory myosin gene occurred after the hominin
      chimpanzee divergence but before the divergence of the human and
      Neandertal/Denisovan lineages. The absence of a functional MYH16 protein may
      explain our relatively reduced jaw muscles; this gene loss may have followed the
      adoption of cooking behavior. In contrast, salivary amylase gene (AMY1)
      duplications were not observed in the Neandertal and Denisovan genomes,
      suggesting a relatively recent origin for the AMY1 copy number gains that are
      observed in modern humans. Thus, if earlier hominins were consuming large
      quantities of starch-rich underground storage organs, as previously hypothesized,
      then they were likely doing so without the digestive benefits of increased
      salivary amylase production. Our most surprising result was the observation of a
      heterozygous mutation in the first codon of the TAS2R38 bitter taste receptor
      gene in the Neandertal individual, which likely would have resulted in a non
      functional protein and inter-individual PTC (phenylthiocarbamide) taste
      sensitivity variation, as also observed in both humans and chimpanzees. 

PMID- 25563410
TI  - Developing and testing a framework for evaluating the quality of comprehensive
      family assessment in child welfare.
AB  - Over the last decade, Comprehensive Family Assessment (CFA) has become a best
      practice in child welfare. Comprehensive Family Assessments go beyond risk
      assessment to develop a full picture of the child's and family's situation. When
      appropriately synthesized, assessment information can lead to a clear
      articulation of the patterns of child or family functioning which are related to
      child abuse and maltreatment or which can be strengthened to facilitate change.
      This study defines and provides concrete examples of dimensions of quality in
      child welfare assessment reports that are consistent with the CFA guidelines and
      best practices embraced by child welfare agencies, courts, and other key
      stakeholders. Leveraging a random assignment design, the study compares the
      quality of reports written by a caseworker alone versus those written by a
      caseworker paired with a licensed Integrated Assessment (IA) screener. Findings
      are discussed in the context of the dual professional model and factors
      contributing to the timely completion of high quality assessment reports. 

PMID- 25563411
TI  - Safety assessment of FDA-approved (orlistat and lorcaserin) anti-obesity
      medications.
AB  - INTRODUCTION: Options for treating obesity remain limited despite it being a
      chronic, recurrent and morbid condition. New drugs that are proposed for its
      treatment encounter strong reluctance by regulatory agencies and many doctors.
      AREAS COVERED: This review will focus on the safety of an older drug, orlistat
      (the only one still approved in the European Union) and a newer recently FDA
      approved one, lorcaserin. Both are approved as long-term monotherapy for obesity
      in the United States of America and they have demonstrated median weight loss of
      nearly 3% over placebo. EXPERT OPINION: Research, development and approval of new
      anti-obesity drugs are necessary for improved management of this chronic
      condition. Orlistat and lorcaserin are two FDA-approved drugs with limited
      overall efficacy. Nevertheless they are useful weapons for at least some obese
      individuals. Orlistat has a long and solid safety profile, whereas the safety of
      lorcaserin is still a matter of debate, mainly due to a lack of long-term data.
      However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes
      concerns about valvulopathy associated with other serotonin agonists, such as
      fenfluramine.

PMID- 25563412
TI  - Can numerical modeling help understand the fate of tau protein in the axon
      terminal?
AB  - In this paper, we used mathematical modeling to investigate the fate of tau
      protein in the axon terminal. We developed a comprehensive model of tau transport
      that accounts for transport of cytosolic tau by diffusion, diffusion transport of
      microtubule (MT)-bound tau along the MT lattice, active motor-driven transport of
      MT-bound tau via slow axonal transport mechanism, and degradation of tau in the
      axon due to tau's finite half-life. We investigated the effect of different
      assumptions concerning the fate of tau in the terminal on steady-state transport
      of tau in the axon. In particular, we studied two possible scenarios: (i) tau is
      destroyed in the terminal and (ii) there is no tau destruction in the terminal,
      and to avoid tau accumulation we postulated zero flux of tau at the terminal. We
      found that the tau concentration and percentage of MT-bound tau are not very
      sensitive to the assumption concerning the fate of tau in the terminal, but the
      tau's flux and average velocity of tau transport are very sensitive to this
      assumption. This suggests that measuring the velocity of tau transport and
      comparing it with the results of mathematical modeling for different assumptions
      concerning tau's fate in the terminal can provide information concerning what
      happens to tau in the terminal. 

PMID- 25563413
TI  - Advances in the molecular functions of syndecan-1 (SDC1/CD138) in the
      pathogenesis of malignancies.
AB  - Syndecan-1 (SDC1, synd, CD138) is the most widely studied member of four
      structurally related cell surface heparan sulfate proteoglycans (HSPG). Although
      SDC1 has been implicated in a wide range of biological functions, its altered
      expression often produces malignant phenotypes, which arise from increased cell
      proliferation and cell growth, cell survival, cell invasion and metastasis, and
      angiogenesis. Recent studies revealed much about the underlying molecular roles
      of SDC1 in these processes. The changes in SDC1 expression also have a direct
      impact on the clinical course of cancers, as evident by its prognostic
      significance. Accumulating evidence suggest that SDC1 is involved in stimulation
      of cancer stem cells (CSC) or tumor initiating cells (TIC) and this may affect
      disease relapse, and resistance to therapy. This review discusses the progress on
      the pro-tumorigenic role(s) of SDC1 and how these roles may impact the clinical
      aspect of the disease. Also discussed, are the current strategies for targeting
      SDC1 or its related signaling. 

PMID- 25563414
TI  - Development of clinical recommendations for progressive return to activity after
      military mild traumatic brain injury: guidance for rehabilitation providers.
AB  - OBJECTIVE: Previously published mild traumatic brain injury (mTBI) management
      guidelines provide very general recommendations to return individuals with mTBI
      to activity. This lack of specific guidance creates variation in military
      rehabilitation. The Office of the Army Surgeon General in collaboration with the
      Defense and Veterans Brain Injury Center, a component center of the Defense
      Centers of Excellence for Psychological Health and Traumatic Brain Injury,
      convened an expert working group to review the existing literature and propose
      clinical recommendations that standardize rehabilitation activity progression
      following mTBI. PARTICIPANTS: A Progressive Activity Working Group consisted of
      11 Department of Defense representatives across all service branches, 7 Defense
      Centers of Excellence for Psychological Health and Traumatic Brain Injury
      representatives, and 8 academic/research/civilian experts with experience
      assessing and treating individuals with mTBI for return to activity. An expert
      working group meeting included the Progressive Activity Working Group and 15
      additional subject matter experts. METHODS: In February 2012, the Progressive
      Activity Working Group was established to determine the need and purpose of the
      rehabilitation recommendations. Following literature review, a table was created
      on the basis of the progression from the Zurich consensus statement on concussion
      in sport. Issues were identified for discussion with a meeting of the larger
      expert group during a July 2012 conference. Following development of
      rehabilitation guidance, the Defense Centers of Excellence for Psychological
      Health and Traumatic Brain Injury coordinated a similar process for military
      primary care providers. RESULTS: End products for rehabilitation and primary care
      providers include specific recommendations for return to activity after
      concussion. A 6-stage progression specifies activities in physical, cognitive,
      and balance/vestibular domains and allows for resumption of activity for those
      with low-level or preinjury symptom complaints. CONCLUSIONS: The clinical
      recommendations for progressive return to activity represent an important effort
      to standardize activity progression across functional domains and offer providers
      duty-specific activities to incorporate into intervention. Recommendations were
      released in January 2014.

PMID- 25563415
TI  - Bioinformatic Suggestions on MiSeq-Based Microbial Community Analysis.
AB  - Recent sequencing technology development has revolutionized fields of microbial
      ecology. MiSeq-based microbial community analysis allows us to sequence more than
      a few hundred samples at a time, which is far more cost-effective than
      pyrosequencing. The approach, however, has not been preferably used owing to
      computational difficulties of processing huge amounts of data as well as known
      Illumina-derived artefact problems with amplicon sequencing. The choice of
      assembly software to take advantage of paired-end sequencing and methods to
      remove Illumina artefacts sequences are discussed. The protocol we suggest not
      only removed erroneous reads, but also dramatically reduced computational
      workload, which allows even a typical desktop computer to process a huge amount
      of sequence data generated with Illumina sequencers. We also developed a Web
      interface (http://biotech.jejunu.ac.kr/ ~abl/16s/) that allows users to conduct
      fastq-merging and mothur batch creation. The study presented here should provide
      technical advantages and supports in applying MiSeq-based microbial community
      analysis. 

PMID- 25563416
TI  - Dictyostelium discoideum Ax2 as an Assay System for Screening of Pharmacological
      Chaperones for Phenylketonuria Mutations.
AB  - In this study, we developed an assay system for missense mutations in human
      phenylalanine hydroxylases (hPAHs). To demonstrate the reliability of the system,
      eight mutant proteins (F39L, K42I, L48S, I65T, R252Q, L255V, S349L, and R408W)
      were expressed in a mutant strain (pah(-)) of Dictyostelium discoideum Ax2
      disrupted in the indigenous gene encoding PAH. The transformed pah- cells grown
      in FM minimal medium were measured for growth rate and PAH activity to reveal a
      positive correlation between them. The protein level of hPAH was also determined
      by western blotting to show the impact of each mutation on protein stability and
      catalytic activity. The result was highly compatible with the previous ones
      obtained from other expression systems, suggesting that Dictyostelium is a
      dependable alternative to other expression systems. Furthermore, we found that
      both the protein level and activity of S349L and R408W, which were impaired
      severely in protein stability, were rescued in HL5 nutrient medium. Although the
      responsible component(s) remains unidentified, this unexpected finding showed an
      important advantage of our expression system for studying unstable proteins. As
      an economic and stable cell-based expression system, our development will
      contribute to mass-screening of pharmacological chaperones for missense PAH
      mutations as well as to the in-depth characterization of individual mutations. 

PMID- 25563417
TI  - H9 induces apoptosis via the intrinsic pathway in non-small-cell lung cancer A549
      cells.
AB  - H9 is an ethanol extract prepared from nine traditional/medicinal herbs. This
      study was focused on the anticancer effect of H9 in non-small-cell lung cancer
      cells. The effects of H9 on cell viability, apoptosis, mitochondrial membrane
      potential (MMP; Deltaphim), and apoptosis-related protein expression were
      investigated in A549 human lung cancer cells. In this study, H9-induced apoptosis
      was confirmed by propidium iodide staining, expression levels of mRNA were
      determined by reverse transcriptase polymerase chain reaction, protein expression
      levels were checked by western blot analysis, and MMP (Deltaphim) was measured by
      JC- 1 staining. Our results indicated that H9 decreased the viability of A549
      cells and induced cell morphological changes in a dose-dependent manner. H9 also
      altered expression levels of molecules involved in the intrinsic signaling
      pathway. H9 inhibited Bcl-xL expression, whereas Bax expression was enhanced and
      cytochrome C was released. Furthermore, H9 treatment led to the activation of
      caspase-3/caspase-9 and proteolytic cleavage of poly(ADPribose) polymerase; the
      MMP was collapsed by H9. However, the expression levels of extrinsic pathway
      molecules such as Fas/FasL, TRAIL/TRAIL-R, DR5, and Fas-associated death receptor
      were downregulated by H9. These results indicated that H9 inhibited proliferation
      and induced apoptosis by activating intrinsic pathways but not extrinsic pathways
      in human lung cancer cells. Our results suggest that H9 can be used as an
      alternative remedy for human non-small-cell lung cancer.

PMID- 25563419
TI  - Batch conversion of methane to methanol using Methylosinus trichosporium OB3b as
      biocatalyst.
AB  - Recently, methane has attracted much attention as an alternative carbon feedstock
      since it is the major component of abundant shale and natural gas. In this work,
      we produced methanol from methane using whole cells of Methylosinus trichosporium
      OB3b as the biocatalyst. M. trichosporium OB3b was cultured on NMS medium with a
      supply of 7:3 air/methane ratio at 30 degrees C. The optimal concentrations of
      various methanol dehydrogenase inhibitors such as potassium phosphate and EDTA
      were determined to be 100 and 0.5 mM, respectively, for an efficient production
      of methanol. Sodium formate (40 mM) as a reducing power source was added to
      enhance the conversion efficiency. A productivity of 49.0 mg/l.h, titer of 0.393
      g methanol/l, and conversion of 73.8% (mol methanol/mol methane) were obtained
      under the optimized batch condition. 

PMID- 25563418
TI  - Peroxisome proliferator-activated receptor-gamma agonist 4-O-methylhonokiol
      induces apoptosis by triggering the intrinsic apoptosis pathway and inhibiting
      the PI3K/Akt survival pathway in SiHa human cervical cancer cells.
AB  - 4-O-Methylhonokiol (MH), a bioactive compound derived from Magnolia officinalis,
      is known to exhibit antitumor effects in various cancer cells. However, the
      precise mechanism of its anticancer activity in cervical cancer cells has not yet
      been studied. In this study, we demonstrated that MH induces apoptosis in SiHa
      cervical cancer cells by enhancing peroxisome proliferator-activated receptor
      gamma (PPARgamma) activation, followed by inhibition of the PI3K/Akt pathway and
      intrinsic pathway induction. MH upregulated PPARgamma and PTEN expression levels
      while it decreased p-Akt in the MH-induced apoptotic process, thereby supporting
      the fact that MH is a PPARgamma activator. Additionally, MH decreased the
      expression of Bcl-2 and Bcl-XL, inducing the intrinsic pathway in MH-treated SiHa
      cells. Furthermore, MH treatment led to the activation of caspase-3/caspase-9 and
      proteolytic cleavage of polyADP ribose polymerase. The expression levels of Fas
      (CD95) and E6/E7 oncogenes were not altered by MH treatment. Taken together, MH
      activates PPARgamma/PTEN expression and induces apoptosis via suppression of the
      PI3K/Akt pathway and mitochondria-dependent pathways in SiHa cells. These
      findings suggest that MH has potential for development as a therapeutic agent for
      human cervical cancer. 

PMID- 25563420
TI  - Screening, Gene Cloning, and Characterizations of an Acid-Stable alpha-Amylase.
AB  - Based on its alpha-amylase activity at pH 5.0 and optimal pH of the crude enzyme,
      a strain (named B-5) with acid alpha-amylase production was screened. The B-5
      strain was identified as Bacillus amyloliquefaciens through morphological,
      physiological, and biochemical characteristics analysis, as well as 16S rDNA
      phylogenetic analysis. Its alpha-amylase gene of GenBank Accession No. GU318401
      was cloned and expressed in Escherichia coli. The purified recombinant alpha
      amylase AMY-Ba showed the optimal pH of 5.0, and was stable at a pH range of 4.0
      6.0. When hydrolyzing soluble starch, amylose, and amylopectin, AMY-Ba released
      glucose and maltose as major end products. The alpha-amylase AMY-Ba in this work
      was a different type from the well-investigated J01542 (GenBank Accession No.)
      type alpha-amylase from the same species. AMY-Ba exhibited notable adsorption and
      hydrolysis ability towards various raw starches. Structure analysis of AMY-Ba
      suggested the presence of a new starch-binding domain at its C-terminal region. 

PMID- 25563421
TI  - Radical Scavenging Activities of Undaria pinnatifida Extracts Fermented with
      Cordyceps militaris Mycelia.
AB  - The present study was performed to investigate the various radical scavenging
      activities of fermented Undaria pinnatifida by the mycelia fermentation method.
      U. pinnatifida was fermented with Cordyceps militaris (C. militaris) mycelia
      using solid culture and compared with unfermentated U. pinnatifida and C.
      militaris mycelia for antioxidant activities. The various radical scavenging
      activities of extracts from U. pinnatifida fermented with C. militaris mycelia
      (FUCM) were evaluated by electron spin resonance. The antioxidant activities of
      the FUCM extracts were assayed for ferric reducing antioxidant power, 2,2'
      azinobis-(3- ethybenzothiazoline-6-sulfonic acid) radical scavenging activity,
      and oxygen radical absorption capacity. The free radical scavenging activity of
      FUCM extracts was higher than that of C. militaris mycelia or U. pinnatifida
      alone. FUCM extracts were significantly (p < 0.05) increased up to 35 times, 10
      times, and 16 times that of U. pinnatifida extracts on DPPH, alkyl, and hydroxyl
      radical scavenging activities, respectively. These results indicate that FUCM
      extracts have different chemical ingredients from U. pinnatifida and could
      provide beneficial antioxidant activity. 

PMID- 25563422
TI  - Chemical Genetics Approach Reveals Importance of cAMP and MAP Kinase Signaling to
      Lipid and Carotenoid Biosynthesis in Microalgae.
AB  - In this study, we attempted to understand signaling pathways behind lipid
      biosynthesis by employing a chemical genetics approach based on small molecule
      inhibitors. Specific signaling inhibitors of MAP kinase or modulators of cAMP
      signaling were selected to evaluate the functional roles of each of the key
      signaling pathways in three different microalgal species: Chlamydomonas
      reinhardtii, Chlorella vulgaris, and Haematococcus pluvialis. Our results clearly
      indicate that cAMP signaling pathways are indeed positively associated with
      microalgal lipid biosynthesis. In contrast, MAP kinase pathways in three
      microalgal species are all negatively implicated in both lipid and carotenoid
      biosynthesis.

PMID- 25563423
TI  - Emerging frontiers of graphene in biomedicine.
AB  - Graphene is a next-generation biomaterial with increasing biomedical
      applicability. As a new class of one-atom-thick nanosheets, it is a true two
      dimensional honeycomb network nanomaterial that attracts interest in various
      scientific fields and is rapidly becoming the most widely studied carbon-based
      material. Since its discovery in 2004, its unique optical, mechanical,
      electronic, thermal, and magnetic properties are the basis of exploration of the
      potential applicability of graphene. Graphene materials, such as graphene oxide
      and its reduced form, are studied extensively in the biotechnology arena owing to
      their multivalent functionalization and efficient surface loading with various
      biomolecules. This review provides a brief summary of the recent progress in
      graphene and graphene oxide biological research together with current findings to
      spark novel applications in biomedicine. Graphene-based applications are
      progressively developing; hence, the opportunities and challenges of this rapidly
      growing field are discussed together with the versatility of these multifaceted
      materials.

PMID- 25563424
TI  - Electrochemically responsive heterogeneous catalysis for controlling reaction
      kinetics.
AB  - We report a method to control reaction kinetics using electrochemically
      responsive heterogeneous catalysis (ERHC). An ERHC system should possess a hybrid
      structure composed of an electron-conducting porous framework coated with redox
      switchable catalysts. In contrast to other types of responsive catalysis, ERHC
      combines all the following desired characteristics for a catalysis control
      strategy: continuous variation of reaction rates as a function of the magnitude
      of external stimulus, easy integration into fixed-bed flow reactors, and precise
      spatial and temporal control of the catalyst activity. Herein we first
      demonstrate a facile approach to fabricating a model ERHC system that consists of
      carbon microfibers with conformal redox polymer coating. Second, using a Michael
      reaction whose kinetics depends on the redox state of the redox polymer catalyst,
      we show that use of different electrochemical potentials permits continuous
      adjustment of the reaction rates. The dependence of the reaction rate on the
      electrochemical potential generally agrees with the Nernstian prediction, with
      minor discrepancies due to the multilayer nature of the polymer film.
      Additionally, we show that the ERHC system can be employed to manipulate the
      shape of the reactant concentration-time profile in a batch reactor through
      applying customized potential-time programs. Furthermore, we perform COMSOL
      simulation for an ERHC-integrated flow reactor, demonstrating highly flexible
      manipulation of reactant concentrations as a function of both location and time. 

PMID- 25563426
TI  - Do lymphocytes count in myeloma? Are we absolutely sure?

PMID- 25563425
TI  - Novel therapeutic options for relapsed hairy cell leukemia.
AB  - The majority of patients with hairy cell leukemia (HCL) achieve a response to
      therapy with cladribine or pentostatin with or without rituximab. However, late
      relapses can occur. Treatment of relapsed HCL can be difficult due to a poor
      tolerance to chemotherapy, increased risk of infections and decreased
      responsiveness to chemotherapy. The identification of BRAFV600E mutations and the
      role of aberrant MEK kinase and Bruton's tyrosine kinase (BTK) pathways in the
      pathogenesis of HCL have helped to develop novel targeted therapies for these
      patients. Currently, the most promising therapeutic strategies for relapsed or
      refractory HCL include recombinant immunoconjugates targeting CD22 (e.g.
      moxetumomab pasudotox), BRAF inhibitors such as vemurafenib and B cell receptor
      signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular
      variant of classic HCL has been identified to be less responsive to chemotherapy.
      Herein, we review the results of the ongoing clinical trials and potential future
      therapies for relapsed/refractory HCL. 

PMID- 25563427
TI  - Impact of vancomycin-resistant enterococcal bacteremia on outcome during acute
      myeloid leukemia induction therapy.
AB  - This study aimed to identify the rate and impact of vancomycin-resistant
      enterococcal (VRE) bacteremia in patients with acute myeloid leukemia (AML)
      receiving induction chemotherapy (IC). Thirty-seven (10.6%) of 350 patients had
      VRE bacteremia during IC, with increasing rates of VRE bacteremia over the course
      of the study period. The overall complete remission (CR) rate for the cohort was
      73%, and there was no difference in CR rate between the VRE bacteremia and non
      VRE bacteremia cohorts (70% vs. 73%, p = 0.70). Unadjusted median overall
      survival (OS) was 12.8 months, and differed significantly between those with and
      without VRE bacteremia (7.1 months vs. 13.1 months, respectively; p = 0.03). The
      presence of VRE bacteremia during IC for AML was independently associated with
      increased all-cause mortality (hazard ratio 1.72, 95% confidence interval 1.13
      2.63, p = 0.01). 

PMID- 25563430
TI  - Iron(II) complexes of tridentate indazolylpyridine ligands: enhanced spin
      crossover hysteresis and ligand-based fluorescence.
AB  - Reaction of 2,6-difluoropyridine with 2 equiv of indazole and NaH at room
      temperature affords a mixture of 2,6-bis(indazol-1-yl)pyridine (1-bip), 2
      (indazol-1-yl)-6-(indazol-2-yl)pyridine (1,2-bip), and 2,6-bis(indazol-2
      yl)pyridine (2-bip), which can be separated by solvent extraction. A two-step
      procedure using the same conditions also affords both 2-(indazol-1-yl)-6-(pyrazol
      1-yl)pyridine (1-ipp) and 2-(indazol-2-yl)-6-(pyrazol-1-yl)pyridine (2-ipp).
      These are all annelated analogues of 2,6-di(pyrazol-1-yl)pyridine, an important
      ligand for spin-crossover complexes. Iron(II) complexes [Fe(1-bip)2](2+), [Fe(1,2
      bip)2](2+), and [Fe(1-ipp)2](2+) are low-spin at room temperature, reflecting
      sterically imposed conformational rigidity of the 1-indazolyl ligands. In
      contrast, the 2-indazolyl complexes [Fe(2-bip)2](2+) and [Fe(2-ipp)2](2+) are
      high-spin in solution at room temperature, whereas salts of [Fe(2-bip)2](2+)
      exhibit thermal spin transitions in the solid state. Notably, [Fe(2
      bip)2][BF4]2.2MeNO2 adopts a terpyridine embrace lattice structure and undergoes
      a spin transition near room temperature after annealing, resulting in thermal
      hysteresis that is wider than previously observed for this structure type (T1/2 =
      266 K, DeltaT = 16-20 K). This reflects enhanced mechanical coupling between the
      cations in the lattice through interdigitation of their ligand arms, which
      supports a previously proposed structure/function relationship for spin-crossover
      materials with this form of crystal packing. All of the compounds in this work
      exhibit blue fluorescence in solution under ambient conditions. In most cases,
      the ligand-based emission maxima are slightly red shifted upon complexation, but
      there is no detectable correlation between the emission maximum and the spin
      state of the iron centers. 

PMID- 25563428
TI  - High-dose chemotherapy with carmustine, etoposide, cytarabine and melphalan
      followed by autologous stem cell transplant is an effective treatment for elderly
      patients with poor-prognosis lymphoma.
AB  - Autologous stem cell transplant (ASCT) after high-dose chemotherapy (HDT)
      increases overall survival when used in relapsed non-Hodgkin lymphoma (NHL) in
      patients under 65 years old. Limited experience is available for older patients.
      We present a retrospective analysis of 73 consecutive patients aged over 65 years
      treated for aggressive or relapsed lymphoma by HDT with carmustine, etoposide,
      cytarabine and melphalan (BEAM) at full dosage followed by ASCT. Patient data
      were obtained from medical charts from two institutions. Median age was 67 years
      (65-74). Significant comorbidities were present in 24.7% of patients. The median
      number of days for grade 4 neutropenia was 9 (5-18). The early treatment-related
      mortality rate (<100 days) was 2.7%. The estimated 2-year progression-free
      survival and overall survival rates were 67.2% and 78.5%, respectively. In
      conclusion, the full-dose HDT-ASCT regimen is feasible, safe and efficient in
      selected patients over 65 years old.

PMID- 25563429
TI  - Phase I dose escalation study of lestaurtinib in patients with myelofibrosis.
AB  - We performed a multicenter, investigator initiated, phase I dose escalation study
      of the oral multi-kinase inhibitor lestaurtinib in patients with JAK2V617F
      positive myelofibrosis, irrespective of baseline platelet count. A total of 34
      patients were enrolled. Dose-limiting toxicities were observed in three patients
      overall, at the 100 mg (n = 1) and 160 mg (n = 2) twice-daily dose levels. The
      maximum tolerated dose was 140 mg twice daily. Gastrointestinal toxicity was the
      most common adverse event. Sixteen patients were evaluable for response at 12
      weeks. Seven patients had clinical improvement by International Working Group -
      Myeloproliferative Neoplasms Research and Treatment criteria. Meaningful
      reductions in JAK2V617F allele burden were not observed. To measure JAK2
      inhibition in vivo, plasma from treated patients was assayed for its ability to
      inhibit phosphorylation of signal transducer and activator of transcription 5
      (STAT5): doses lower than 140 mg had variable and incomplete inhibition. In this
      phase I study, although gastrointestinal adverse events were common, significant
      clinical activity with lestaurtinib was observed (ClinicalTrials.gov identifier:
      NCT00668421). 

PMID- 25563431
TI  - The physical size of transcription factors is key to transcriptional regulation
      in chromatin domains.
AB  - Genetic information, which is stored in the long strand of genomic DNA as
      chromatin, must be scanned and read out by various transcription factors. First,
      gene-specific transcription factors, which are relatively small (~50 kDa), scan
      the genome and bind regulatory elements. Such factors then recruit general
      transcription factors, Mediators, RNA polymerases, nucleosome remodellers, and
      histone modifiers, most of which are large protein complexes of 1-3 MDa in size.
      Here, we propose a new model for the functional significance of the size of
      transcription factors (or complexes) for gene regulation of chromatin domains.
      Recent findings suggest that chromatin consists of irregularly folded nucleosome
      fibres (10 nm fibres) and forms numerous condensed domains (e.g., topologically
      associating domains). Although the flexibility and dynamics of chromatin allow
      repositioning of genes within the condensed domains, the size exclusion effect of
      the domain may limit accessibility of DNA sequences by transcription factors. We
      used Monte Carlo computer simulations to determine the physical size limit of
      transcription factors that can enter condensed chromatin domains. Small gene
      specific transcription factors can penetrate into the chromatin domains and
      search their target sequences, whereas large transcription complexes cannot enter
      the domain. Due to this property, once a large complex binds its target site via
      gene-specific factors it can act as a 'buoy' to keep the target region on the
      surface of the condensed domain and maintain transcriptional competency. This
      size-dependent specialization of target-scanning and surface-tethering functions
      could provide novel insight into the mechanisms of various DNA transactions, such
      as DNA replication and repair/recombination. 

PMID- 25563433
TI  - Parental subfertility, fertility treatment, and the risk of congenital anorectal
      malformations.
AB  - BACKGROUND: Fertility treatment seems to play a role in the etiology of
      congenital anorectal malformations, but it is unclear whether the underlying
      parental subfertility, ovulation induction, or the treatment itself is involved.
      Therefore, we investigated the odds of anorectal malformations among children of
      subfertile parents who conceived with or without treatment compared with fertile
      parents. METHODS: We performed a case-control study among 380 cases with
      anorectal malformations treated at 3 departments of pediatric surgery in The
      Netherlands and 1973 population-based controls born between August 1988 and
      August 2012. Parental questionnaires were used to obtain information on fertility
      related issues and potential confounders. RESULTS: In singletons, increased risks
      of anorectal malformations were observed for parents who underwent
      intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) treatment
      compared with fertile parents (odds ratio = 2.4 [95% confidence interval = 1.0
      5.9] and 4.2 [1.9-8.9], respectively). For subfertile parents who conceived after
      IVF treatment, an elevated risk was also found when they were compared with
      subfertile parents who conceived without treatment (3.2 [1.4-7.2]). Among
      children of the latter category of parents, only the risk of anorectal
      malformations with other major congenital malformations was increased compared
      with fertile parents (2.0 [1.3-3.3]). No associations were found with
      intrauterine insemination or use of hormones for ovulation induction.
      CONCLUSIONS: We found evidence of a role of ICSI and IVF treatments in the
      etiology of anorectal malformations. However, subfertility without treatment
      increased only the risk of anorectal malformations with additional congenital
      malformations.

PMID- 25563432
TI  - Miscarriage among flight attendants.
AB  - BACKGROUND: Cosmic radiation and circadian disruption are potential reproductive
      hazards for flight attendants. METHODS: Flight attendants from 3 US airlines in 3
      cities were interviewed for pregnancy histories and lifestyle, medical, and
      occupational covariates. We assessed cosmic radiation and circadian disruption
      from company records of 2 million individual flights. Using Cox regression
      models, we compared respondents (1) by levels of flight exposures and (2) to
      teachers from the same cities, to evaluate whether these exposures were
      associated with miscarriage. RESULTS: Of 2654 women interviewed (2273 flight
      attendants and 381 teachers), 958 pregnancies among 764 women met study criteria.
      A hypothetical pregnant flight attendant with median first-trimester exposures
      flew 130 hours in 53 flight segments, crossed 34 time zones, and flew 15 hours
      during her home-base sleep hours (10 pm-8 am), incurring 0.13 mGy absorbed dose
      (0.36 mSv effective dose) of cosmic radiation. About 2% of flight attendant
      pregnancies were likely exposed to a solar particle event, but doses varied
      widely. Analyses suggested that cosmic radiation exposure of 0.1 mGy or more may
      be associated with increased risk of miscarriage in weeks 9-13 (odds ratio = 1.7
      [95% confidence interval = 0.95-3.2]). Risk of a first-trimester miscarriage with
      15 hours or more of flying during home-base sleep hours was increased (1.5 [1.1
      2.2]), as was risk with high physical job demands (2.5 [1.5-4.2]). Miscarriage
      risk was not increased among flight attendants compared with teachers.
      CONCLUSIONS: Miscarriage was associated with flight attendant work during sleep
      hours and high physical job demands and may be associated with cosmic radiation
      exposure.

PMID- 25563435
TI  - Pitfalls in post-mortem CT-angiography--intravascular contrast induces post
      mortem pericardial effusion.

PMID- 25563434
TI  - Risk of myocardial infarction immediately after alcohol consumption.
AB  - BACKGROUND: Habitual moderate alcohol consumption is associated with a lower risk
      of acute myocardial infarction (MI), whereas heavy (binge) drinking is associated
      with higher cardiovascular risk. However, less is known about the immediate
      effects of alcohol consumption on the risk of acute MI and whether any
      association differs by beverage type or usual drinking patterns. METHODS: We
      conducted a case-crossover analysis of 3869 participants from the Determinants of
      Myocardial Infarction Onset Study who were interviewed during hospitalization for
      acute MI in one of the 64 medical centers across the United States in 1989-1996.
      We compared the observed number of times that each participant consumed wine,
      beer, or liquor in the hour preceding MI symptom onset with the expected
      frequency based on each participant's control information, defined as the number
      of times the participant consumed alcohol in the past year. RESULTS: Among 3869
      participants, 2119 (55%) reported alcohol consumption in the past year, including
      76 within 1 hour before acute MI onset. The incidence rate of acute MI onset was
      elevated 1.72-fold (95% confidence interval [CI] = 1.37-2.16) within 1 hour after
      alcohol consumption. The association was stronger for liquor than for beer or
      wine. The higher rate was not apparent for daily drinkers. For the 24 hours after
      consumption, there was a 14% lower rate (relative risk = 0.86 [95% CI = 0.79
      0.95]) of MI compared with periods with no alcohol consumption. CONCLUSIONS:
      Alcohol consumption is associated with an acutely higher risk of MI in the
      subsequent hour among people who do not typically drink alcohol daily.

PMID- 25563436
TI  - Association of neutrophil-lymphocyte ratio with impaired aortic elasticity in
      newly diagnosed and never-treated hypertensive patients.
AB  - OBJECTIVES: The aim of our study was to investigate the relationship between
      neutrophil-to-lymphocyte ratio (NLR) and aortic elasticity in patients with newly
      diagnosed essential hypertension (HT). DESIGN: A total of 101 patients with newly
      diagnosed and untreated essential HT and 54 healthy control patients were
      enrolled. Aortic stiffness (beta) index, aortic strain and aortic distensibility
      (AoD) were measured with formulas by using transthoracic echocardiography and
      office blood pressure obtained by sphygmomanometer data. NLR was calculated using
      complete blood count. RESULTS: Patients with HT had significantly higher NLR
      compared with the healthy control group (2.49+/-0.77 vs. 1.80+/-0.65, P<0.001).
      In addition, there were significant differences between the HT and healthy
      control groups in beta index (12.7+/-7.35 vs. 6.97+/-3.3, P<0.001) and AoD (3.0+/
      1.54 vs. 4.85+/-1.35, P<0.001). There was also a statistically significant
      correlation between NLR and beta index (r=0.727, P<0.001) and AoD (r=-0.606,
      P<0.001) parameters in hypertensive patients. CONCLUSION: Our results showed that
      in patients with newly diagnosed and untreated essential HT, increased NLR has
      been significantly linked to impaired aortic elastic properties.

PMID- 25563438
TI  - The interaction of DNA with multi-Cys2His2 zinc finger proteins.
AB  - The multi-Cys2His2 (mC2H2) zinc finger protein, like CTCF, plays a central role
      in the three-dimensional organization of chromatin and gene regulation. The
      interaction between DNA and mC2H2 zinc finger proteins becomes crucial to better
      understand how CTCF dynamically shapes the chromatin structure. Here, we study a
      coarse-grained model of the mC2H2 zinc finger proteins in complexes with DNA, and
      in particular, we study how a mC2H2 zinc finger protein binds to and searches for
      its target DNA loci. On the basis of coarse-grained molecular dynamics
      simulations, we present several interesting kinetic conformational properties of
      the proteins, such as the rotation-coupled sliding, the asymmetrical roles of
      different zinc fingers and the partial binding partial dangling mode. In
      addition, two kinds of studied mC2H2 zinc finger proteins, of CG-rich and AT-rich
      binding motif each, were able to recognize their target sites and slide away from
      their non-target sites, which shows a proper sequence specificity in our model
      and the derived force field for mC2H2-DNA interaction. A further application to
      CTCF shows that the protein binds to a specific DNA duplex only with its central
      zinc fingers. The zinc finger domains of CTCF asymmetrically bend the DNA, but do
      not form a DNA loop alone in our simulations. 

PMID- 25563437
TI  - Understanding smoking after acute illness: An application of the sentinel event
      method.
AB  - The sentinel event theory provides a stepwise approach for building models to
      understand how negative events can spark health behaviour change. This study
      tested a preliminary model using the sentinel events method in a sample (N = 300)
      of smokers who sought care for acute cardiac symptoms. Patients completed
      measures on: smoking-related causal attribution, perceived severity of the acute
      illness event, illness-related fear and intentions to quit smoking. Patients were
      followed up one week after the health event and a seven-day timeline follow back
      was completed to determine abstinence from tobacco. Structural equation models
      were performed using average predictor scale scores at baseline, as well as three
      different time anchors for ratings of illness severity and illness-related fear.
      Quit intentions, actual illness severity and age were the consistent, positive
      and independent predictors of seven-day point prevalence abstinence. Additional
      research on the influences of perceptions and emotional reactions is warranted. 

PMID- 25563439
TI  - Small-angle neutron scattering of nanocrystalline gadolinium and holmium with
      random paramagnetic susceptibility.
AB  - A neutron study of nanocrystalline terbium (Balaji G et al 2008 Phys. Rev. Lett.
      100 227202) has shown that the randomly oriented anisotropy of the paramagnetic
      susceptibility tensor may lead to strongly correlated nanoscale spin disorder in
      the paramagnetic state which can be probed very effectively by magnetic small
      angle neutron scattering (SANS). In principle, this scenario is also applicable
      to other rare-earth metals and the size of the effect is expected to scale with
      the strength of the anisotropy in the paramagnetic state. Here, we report SANS
      results (in the paramagnetic state) on nanocrystalline inert-gas condensed
      samples of Gd and Ho, which represent the cases of low and high anisotropy,
      respectively. 

PMID- 25563440
TI  - Older adults prescribed methadone: a review of the literature across the life
      span from opiate initiation to methadone maintenance treatment.
AB  - Professionals currently working with methadone patients are facing challenges
      with the rise of polydrug use, HIV and Hepatitis epidemics, and treating a large
      volume of individuals who are older than ever before, presenting for the first
      time in their 50's, 60's and 70's. There have been two literature reviews
      conducted on this older population, but they can only provide a snap-shot view on
      the later stage of life of this unique group. A longitudinal literature review of
      the long-term opiate abuser who has transitioned into opiate replacement therapy
      will provide depth and illustrate the complexity of interrelated factors that
      have been affected throughout their life span. This paper reviews the literature
      conducted on opiate addicts from their earlier stages of substance use to older
      adulthood where many have chosen to enter into a methadone maintenance program.
      The paper will also take a biopsychosocial approach when reviewing the literature
      because of how these three domains are deeply affected and interrelated with this
      population. 

PMID- 25563441
TI  - Drivers' visual scanning impairment under the influences of alcohol and
      distraction: a literature review.
AB  - Alcohol intoxication and distraction are two of the leading factors associated
      with impaired driving and fatalities, especially among younger drivers. However,
      it is currently unclear how these conditions affect mechanisms of visual
      attention considered essential for driving. The present article first reviews the
      literature to provide an overview of visual attention as it relates to driving.
      Secondly, the effects of alcohol and distraction on neurocognitive mechanisms of
      visual attention are summarised to provide a background which informs discussion
      of selected driving studies. Visual scanning impairment is identified as a
      consequence of both alcohol and distraction. Thus, experimental studies combining
      the use of simulated driving and eye tracking technologies are selected and
      critically reviewed to assess the relationship between eye movements and driving
      errors as possible indicators of visual scanning impairment. Seven of the eight
      studies selected investigated the effects of distraction while only one addressed
      alcohol. Evaluation of these studies suggests that distraction may affect visual
      scanning by increasing cognitive load which interferes with visual processing.
      The evidence for effects of alcohol on drivers' visual scanning capacity is
      currently scarce due to the lack of research with a specific focus on impairments
      of eye movement in intoxicated drivers. Lack of consistency between studies is
      identified as a current issue which makes it difficult to compare the results of
      different studies. Finally, we note that our strict selection of driving studies
      to avoid greater disparity between them is a limitation of the present review. 

PMID- 25563442
TI  - Salvinorin a and related compounds as therapeutic drugs for psychostimulant
      related disorders.
AB  - Pharmacological treatments are available for alcohol, nicotine, and opioid
      dependence, and several drugs for cannabis-related disorders are currently under
      investigation. On the other hand, psychostimulant abuse and dependence lacks
      pharmacological treatment. Mesolimbic dopaminergic neurons mediate the motivation
      to use drugs and drug-induced euphoria, and psychostimulants (cocaine,
      amphetamine, and methamphetamine) produce their effects in these neurons, which
      may be modulated by the opioid system. Salvinorin A is a kappa-opioid receptor
      agonist extracted from Salvia divinorum, a hallucinogenic plant used in magico
      ritual contexts by Mazateca Indians in Mexico. Salvinorin A and its analogues
      have demonstrated anti-addiction effects in animal models using psychostimulants
      by attenuating dopamine release, sensitization, and other neurochemical and
      behavioral alterations associated with acute and prolonged administration of
      these drugs. The objective of the present article is to present an overview of
      the preclinical evidence suggesting anti-addictive effects of salvinorin A and
      its analogues. 

PMID- 25563444
TI  - A qualitative report on the subjective experience of intravenous psilocybin
      administered in an FMRI environment.
AB  - BACKGROUND: This report documents the phenomenology of the subjective experiences
      of 15 healthy psychedelic experienced volunteers who were involved in a
      functional magnetic resonance imaging (fMRI) study that was designed to image the
      brain effects of intravenous psilocybin. METHODS: The participants underwent a
      semi-structured interview exploring the effects of psilocybin in the MRI scanner.
      These interviews were analysed by Interpretative Phenomenological Analysis. The
      resultant data is ordered in a detailed matrix, and presented in this paper.
      RESULTS: Nine broad categories of phenomenology were identified in the
      phenomenological analysis of the experience; perceptual changes including visual,
      auditory and somatosensory distortions, cognitive changes, changes in mood,
      effects of memory, spiritual or mystical type experiences, aspects relating to
      the scanner and research environment, comparisons with other experiences, the
      intensity and onset of effects, and individual interpretation of the experience.
      DISCUSSION: This article documents the phenomenology of psilocybin when given in
      a novel manner (intravenous injection) and setting (an MRI scanner). The findings
      of the analysis are consistent with previous published work regarding the
      subjective effects of psilocybin. There is much scope for further research
      investigating the phenomena identified in this paper.

PMID- 25563443
TI  - Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction.
AB  - Psilocybin-occasioned mystical experiences have been linked to persisting effects
      in healthy volunteers including positive changes in behavior, attitudes, and
      values, and increases in the personality domain of openness. In an open-label
      pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers
      received 2 or 3 doses of psilocybin in the context of cognitive behavioral
      therapy (CBT) for smoking cessation. Twelve of 15 participants (80%) demonstrated
      biologically verified smoking abstinence at 6-month follow-up. Participants who
      were abstinent at 6 months (n=12) were compared to participants still smoking at
      6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored
      significantly higher on a measure of psilocybin-occasioned mystical experience.
      No significant differences in general intensity of drug effects were found
      between groups, suggesting that mystical-type subjective effects, rather than
      overall intensity of drug effects, were responsible for smoking cessation. Nine
      of 15 participants (60%) met criteria for "complete" mystical experience. Smoking
      cessation outcomes were significantly correlated with measures of mystical
      experience on session days, as well as retrospective ratings of personal meaning
      and spiritual significance of psilocybin sessions. These results suggest a
      mediating role of mystical experience in psychedelic-facilitated addiction
      treatment. 

PMID- 25563445
TI  - A review of lysergic acid diethylamide (LSD) in the treatment of addictions:
      historical perspectives and future prospects.
AB  - Lysergic acid diethylamide (LSD) is a semisynthetic compound with strong
      psychoactive properties. Chemically related to serotonin, LSD was initially
      hypothesized to produce a psychosislike state. Later, LSD was reported to have
      benefits in the treatment of addictions. However, widespread indiscriminate use
      and reports of adverse affects resulted in the classification of LSD as an
      illicit drug with no accepted medical use. This article reviews LSD's storied
      history from its discovery, to its use as a research tool, followed by its
      widespread association with the counterculture movement of the 1960s, and finally
      to its rebirth as a medicine with potential benefits in the treatment of
      addictions. LSD's pharmacology, phenomenology, effects at neurotransmitter
      receptors, and effects on patterns of gene expression are reviewed. Based upon a
      review of the literature, it is concluded that further research into LSD's
      potential as a treatment for addictions is warranted. 

PMID- 25563446
TI  - Psychedelics as medicines for substance abuse rehabilitation: evaluating
      treatments with LSD, Peyote, Ibogaine and Ayahuasca.
AB  - Substances known as psychedelics, hallucinogens and entheogens have been employed
      in ethnomedical traditions for thousands of years, but after promising uses in
      the 1950's and 1960's they were largely prohibited in medical treatment and human
      research starting in the 1970's as part of the fallout from the war on drugs.
      Nonetheless, there are a number of studies which suggest that these substances
      have potential applications in the treatment of addictions. While these
      substances are generally classified as Schedule I, alleging no established
      medical uses and a high drug abuse potential, there is nonetheless evidence
      indicating they might be safe and effective tools for short term interventions in
      addictions treatment. Evidence suggests that the psychedelics have a much greater
      safety profile than the major addictive drugs, having extremely low levels of
      mortality, and producing little if any physical dependence. This paper reviews
      studies evaluating the use of LSD, peyote, ibogaine and ayahuasca in the
      treatment of dependencies and the possible mechanisms underlying the indications
      of effectiveness. Evidence suggests that these substances help assist recovery
      from drug dependency through a variety of therapeutic mechanisms, including a
      notable "after-glow" effect that in part reflects their action on the serotonin
      neurotransmitter system. Serotonin has been long recognized as central to the
      psychedelics' well-known phenomenological, physical, emotional and cognitive
      dynamics. These serotonin-based dynamics are directly relevant to treatment of
      addiction because of depressed serotonin levels found in addict populations, as
      well as the role of serotonin as a neuromodulators affecting many other
      neurotransmitter systems. 

PMID- 25563447
TI  - Crisis intervention related to the use of psychoactive substances in recreational
      settings--evaluating the Kosmicare Project at Boom Festival.
AB  - Kosmicare project implements crisis intervention in situations related to the use
      of psychoactive substances at Boom Festival (Portugal). We present evaluation
      research that aims to contribute to the transformation of the project into an
      evidence-based intervention model. It relies on harm reduction and risk
      minimization principles, crisis intervention models, and Grof's psychedelic
      psychotherapy approach for crisis intervention in situations related to
      unsupervised use of psychedelics. Intervention was expected to produce knowledge
      about the relation between substance use and mental health impact in reducing
      potential risk related to the use of psychoactive substances and mental illness,
      as well as an impact upon target population's views of themselves, their
      relationship to substance use, and to life events in general. Research includes
      data on process and outcome indicators through a mixed methods approach,
      collected next to a sample of n=176 participants. Sample size varied
      considerably, however, among different research measures. 52% of Kosmicare
      visitors reported LSD use. Over 40% also presented multiple drug use. Pre-post
      mental state evaluation showed statistically significant difference (p<.05)
      confirming crisis resolution. Crisis episodes that presented no resolution were
      more often related with mental health outburst episodes, with psychoactive
      substance use or not. Visitors showed high satisfaction with intervention (n=58)
      and according to follow-up (n=18) this perception was stable over time. Crisis
      intervention was experienced as very significant. We discuss limitations and
      implications of evaluating natural setting based interventions, and the relation
      between psychoactive substance use and psychopathology. Other data on visitor's
      profile and vulnerability to crisis showed inconclusive. 

PMID- 25563448
TI  - Ayahuasca, psychedelic studies and health sciences: the politics of knowledge and
      inquiry into an Amazonian plant brew.
AB  - This article offers critical sociological and philosophical reflections on
      ayahuasca and other psychedelics as objects of research in medicine, health and
      human sciences. It situates 21st century scientific inquiry on ayahuasca in the
      broader context of how early modern European social trends and intellectual
      pursuits translated into new forms of empiricism and experimental philosophy, but
      later evolved into a form of dogmatism that convenienced the political
      suppression of academic inquiry into psychedelics. Applying ideas from the field
      of science and technology studies, we consider how ayahuasca's myriad ontological
      representations in the 21st century--for example, plant teacher, traditional
      medicine, religious sacrament, material commodity, cognitive tool, illicit drug-
      influence our understanding of it as an object of inquiry. We then explore
      epistemological issues related to ayahuasca studies, including how the indigenous
      and mestizo concept of "plant teacher" or the more instrumental notion of
      psychedelics as "cognitive tools" may impact understanding of knowledge. This
      leads to questions about whether scientists engaged in ayahuasca research should
      be expected to have personal experiences with the brew, and how these may be
      perceived to help or hinder the objectivity of their pursuits. We conclude with
      some brief reflections on the politics of psychedelic research and impediments to
      academic knowledge production in the field of psychedelic studies.

PMID- 25563449
TI  - What can neuroscience tell us about the potential of psychedelics in healthcare?
      How the neurophenomenology of psychedelics research could help us to flourish
      throughout our lives, as well as to enhance our dying.
AB  - Health-related psychedelic research should focus on helping us flourish, not just
      remedying ill-health or addiction. We don't know enough about how psychedelics
      could enhance human flourishing. Factors promoting health-through-flourishing
      include finding meaning in life, spiritual practices, comfortable levels of
      social bonds, emotionally/physically satisfying sex in a long-term monogamous
      relationship and control over one's daily life. Psychedelic research could find
      more. Neuroscience anchors psychedelic research into disease and disorder, e.g.
      addiction, PSTD, migraine, anxiety, pain etc. Neurophenomenological psychedelics
      research could illuminate relationships between health, ASC/NOSCs and cognitive
      liberty to promote human flourishing. If we accept the self as an epiphenomenon
      of subsystems within the brain, we 'know' 'unconsciously', but are not aware of,
      many things which affect our lives profoundly. These include control over
      identifying, remembering and forgetting our states of mind and how to move
      between them. A prerequisite for integrated investigations into ASC/NOSCs is the
      establishment of a taxonomic knowledge base which lists, categorises and
      characterises ASC/NOSCs to enable us to choose specific states of mind and move
      securely among them. Or, in other words, to enable us to exercise our cognitive
      liberty safely. I believe that human health and flourishing would be enhanced
      were we able to direct our states of being by consciously choosing them. Given
      the promise of mindfulness techniques to enhance our health, happiness and
      spiritual growth, constructing both personal and generic classifications of
      salient ASC/NOSCs makes sense. Laws need to change. The neuroscience of pleasure,
      love, spirituality, decision-making, pattern recognition and location of meaning
      should inform health-enhancing psychedelic research while promoting flourishing
      through cognitive liberty. As part of cognitive liberty, our end-of-life choices
      should include how we die. In other words, our idea of the good death should
      include access to psychedelics. Dying high is increasingly likely to become a
      popular choice as baby boomers age and place their economic clout behind the
      reform of end-of-life laws as well as drug laws. Achieving such crucial legal
      changes depends partly on the ability to produce research to anchor evidence
      based law and policy. Research into psychedelics, ASC/NOSCs and the neurobiology
      of the dying process is essential. 

PMID- 25563450
TI  - Improving financial access to health care in the Kisantu district in the
      Democratic Republic of Congo: acting upon complexity.
AB  - BACKGROUND: Comzmercialization of health care has contributed to widen inequities
      between the rich and the poor, especially in settings with suboptimal regulatory
      frameworks of the health sector. Poorly regulated fee-for-service payment systems
      generate inequity and initiate a vicious circle in which access to quality health
      care gradually deteriorates. Although the abolition of user fees is high on the
      international health policy agenda, the sudden removal of user fees may have
      disrupting effects on the health system and may not be affordable or sustainable
      in resource-constrained countries, such as the Democratic Republic of Congo.
      METHODS AND RESULTS: Between 2008 and 2011, the Belgian development aid agency
      (BTC) launched a set of reforms in the Kisantu district, in the province of Bas
      Congo, through an action-research process deemed appropriate for the
      implementation of change within open complex systems such as the Kisantu local
      health system. Moreover, the entire process contributed to strengthen the
      stewardship capacity of the Kisantu district management team. The reforms mainly
      comprised the rationalization of resources and the regulation of health services
      financing. Flat fees per episode of disease were introduced as an alternative to
      fee-for-service payments by patients. A financial subsidy from BTC allowed to
      reduce the height of the flat fees. The provision of the subsidy was made
      conditional upon a range of measures to rationalize the use of resources.
      CONCLUSIONS: The results in terms of enhancing people access to quality health
      care were immediate and substantial. The Kisantu experience demonstrates that a
      systems approach is essential in addressing complex problems. It provides useful
      lessons for other districts in the country.

PMID- 25563451
TI  - Towards reframing health service delivery in Uganda: the Uganda Initiative for
      Integrated Management of Non-Communicable Diseases.
AB  - BACKGROUND: The burden of non-communicable diseases (NCDs) in low- and middle
      income countries (LMICs) is accelerating. Given that the capacity of health
      systems in LMICs is already strained by the weight of communicable diseases,
      these countries find themselves facing a double burden of disease. NCDs
      contribute significantly to morbidity and mortality, thereby playing a major role
      in the cycle of poverty, and impeding development. METHODS: Integrated approaches
      to health service delivery and healthcare worker (HCW) training will be necessary
      in order to successfully combat the great challenge posed by NCDs. RESULTS: In
      2013, we formed the Uganda Initiative for Integrated Management of NCDs (UINCD),
      a multidisciplinary research collaboration that aims to present a systems
      approach to integrated management of chronic disease prevention, care, and the
      training of HCWs. DISCUSSION: Through broad-based stakeholder engagement,
      catalytic partnerships, and a collective vision, UINCD is working to reframe
      integrated health service delivery in Uganda.

PMID- 25563452
TI  - Epidermal Growth Factor Receptor Expression in Spindle Cell Carcinomas of the
      Head and Neck.
AB  - Spindle cell carcinoma (SpCC) is an uncommon head and neck squamous cell
      carcinoma (SCC) variant consisting of spindled and/or pleomorphic cells with
      epithelial differentiation. Epidermal growth factor receptor (EGFR) is expressed
      by >90 % of conventional SCC, and high level expression is associated with a
      poorer prognosis. Anti-EGFR therapies are commonly used to treat head and neck
      SCC. However, no studies have evaluated EGFR expression in SpCC. Cases of SpCC
      were retrieved from department files. The diagnosis required either a biphasic
      lesion with a squamous neoplastic component, or a purely spindle cell or
      pleomorphic tumor with immunohistochemical positivity for epithelial markers.
      EGFR immunohistochemistry was performed and was quantified in quartiles. Medical
      records were reviewed for clinical follow up information. EGFR was expressed in
      21/30 (70 %) cases, including in the squamous component in 18/19 (95 %) and the
      spindle cell component in only 12/30 (40 %). Where the spindle cell component was
      positive, the intensity and distribution were lower than for the squamous
      component. Recurrent tumors were predominantly (80-90 %) of the spindle cell
      component, and had low (or absent) EGFR expression. Kaplan-Meier survival
      analysis showed no statistically significant differences in overall or disease
      free survival between the EGFR expressing and non-expressing groups (p = 0.414
      and 0.19, respectively). SpCCs of the head and neck have a poor prognosis, and
      markedly reduced EGFR expression. EGFR-specific therapies may not be ideal for
      SpCC patients, which may lack EGFR expression, but further studies are needed.

PMID- 25563453
TI  - Reduced recognition of dynamic facial emotional expressions and emotion-specific
      response bias in children with an autism spectrum disorder.
AB  - Emotion labelling was evaluated in two matched samples of 6-14-year old children
      with and without an autism spectrum disorder (ASD; N = 45 and N = 50, resp.),
      using six dynamic facial expressions. The Emotion Recognition Task proved to be
      valuable demonstrating subtle emotion recognition difficulties in ASD, as we
      showed a general poorer emotion recognition performance, in addition to some
      emotion-specific impairments in the ASD group. Participants' preference for
      selecting a certain emotion label, irrespective of the stimulus presented, played
      an important role in our results: response bias-corrected data still showed an
      overall decreased emotion recognition performance in ASD, but no emotion-specific
      impairments anymore. Moreover, ASD traits and empathy were correlated with
      emotion recognition performance.

PMID- 25563454
TI  - Effectiveness of community-based early intervention based on pivotal response
      treatment.
AB  - Preschoolers (n = 118) with autism spectrum disorder (ASD) participated in this
      prospective effectiveness study of an early intervention program. Treatment
      entailed parent training and therapist-implemented components, incorporating
      Pivotal Response Treatment and Positive Behaviour Support. Standardized ability
      and behavioural measures were gathered prior to and following the 1-year
      intervention. Analyses were conducted for three groups based on baseline IQ:
      Higher IQ (>= 70; n = 36), Moderately Low IQ (40-69; n = 40), and Very Low IQ
      (<40, n = 42). Observed gains in key language and cognitive outcomes were
      significant for all groups. Baseline cognitive scores significantly predicted 1
      year outcomes. Results are encouraging for this relatively low-intensity
      community-based intervention program.

PMID- 25563455
TI  - Detail and gestalt focus in individuals with optimal outcomes from autism
      spectrum disorders.
AB  - Individuals with high-functioning autism (HFA) have a cognitive style that
      privileges local over global or gestalt details. While not a core symptom of
      autism, individuals with HFA seem to reliably show this bias. Our lab has been
      studying a sample of children who have overcome their early ASD diagnoses,
      showing "optimal outcomes" (OO). This study characterizes performance by OO, HFA,
      and typically developing (TD) adolescents as they describe paintings under
      cognitive load. Analyses of detail focus in painting descriptions indicated that
      the HFA group displayed significantly more local focus than both OO and TD
      groups, while the OO and TD groups did not differ. We discuss implications for
      the centrality of detail focus to the autism diagnosis. 

PMID- 25563456
TI  - A phase I study of high-dose calcitriol in combination with temozolomide for
      patients with metastatic melanoma.
AB  - BACKGROUND: Temozolomide is efficacious as an oral alternative for patients with
      metastatic melanoma (MM). Calcitriol has anti-proliferative properties and
      vitamin D receptor (VDR) polymorphisms are associated with alterations in
      melanoma susceptibility and progression. METHODS: Tem 150 mg/m2 was administered
      on days 2-8 and 16-22 every 28 days. Calcitriol was given on days 1 and 15 every
      28 days. VDR gene analysis was completed using PCR-RFLP based assays.
      Tolerability was the primary objective with secondary objectives of time to
      progression (TTP) and overall survival (OS). RESULTS: Twenty pts with MM were
      registered. Cytopenias and thrombosis were the most common grade 3 or 4
      toxicities. Median TTP was 1.8 mo. Pts with high-risk VDR genotype tt+/-ff (n =
      6) had an OS of 3.8 mo from time of enrollment, compared to 7.4 mo for those with
      non-tt/ff genotypes (n = 11), although not statistically significant (HR = 1.20,
      95% CI 0.41-3.53, p = 0.74). CONCLUSIONS: The extended dosing of Tem with
      calcitriol is a well-tolerated regimen. The trend toward improved OS in non-tt/ff
      VDR genotypes is consistent with prior studies associating the tt/ff genotype
      with biologic aggressiveness.

PMID- 25563457
TI  - Community engagement for big epidemiology: deliberative democracy as a tool.
AB  - Public trust is critical in any project requiring significant public support,
      both in monetary terms and to encourage participation. The research community has
      widely recognized the centrality of public trust, garnered through community
      consultation, to the success of large-scale epidemiology. This paper examines the
      potential utility of the deliberative democracy methodology within the public
      health research setting. A deliberative democracy event was undertaken in
      Tasmania, Australia, as part of a wider program of community consultation
      regarding the potential development of a Tasmanian Biobank. Twenty-five
      Tasmanians of diverse backgrounds participated in two weekends of deliberation;
      involving elements of information gathering; discussion; identification of issues
      and formation of group resolutions. Participants demonstrated strong support for
      a Tasmanian Biobank and their deliberations resulted in specific proposals in
      relation to consent; privacy; return of results; governance; funding; and,
      commercialization and benefit sharing. They exhibited a high degree of
      satisfaction with the event, and confidence in the outcomes. Deliberative
      democracy methodology is a useful tool for community engagement that addresses
      some of the limitations of traditional consultation methods. 

PMID- 25563458
TI  - Promoting Precision Cancer Medicine through a Community-Driven Knowledgebase.
AB  - Increasing efforts are being dedicated towards improving cancer care via
      personalized medicine. These efforts depend to a large degree on the availability
      of a knowledge foundation. Unfortunately, existing knowledge linking cancer drugs
      and potential efficacy biomarkers is in its infancy; and where links are known,
      they are frequently unstructured and poorly documented. We have developed a new
      open-access knowledgebase for precision cancer medicine (the PCM Wiki and
      Knowledgebase). This knowledgebase was constructed using an innovative, two
      pronged approach involving a structured knowledgebase at the back-end, and an
      intuitive knowledge-sharing interface and user-friendly query engine in front.
      The knowledgebase was seeded with several patient case reports and information
      was mined via text-mining and literature review by human curators. Using our
      novel Wiki-based platform to present and share knowledge stored in the PCM
      knowledgebase, users are able to suggest corrections, propose additions or point
      to errors in the knowledgebase. The result is a community-driven evolving
      knowledgebase holding integrated and consolidated knowledge of markers and
      indications for personalized cancer medicine. We suggest that the PCM
      Knowledgebase and Wiki could serve as an important tool for the advancement of
      clinical trials and care in the field of precision cancer medicine. 

PMID- 25563459
TI  - A Longitudinal Study of Health Improvement in the Atlanta CHDWB Wellness Cohort.
AB  - The Center for Health Discovery and Wellbeing (CHDWB) is an academic program
      designed to evaluate the efficacy of clinical self-knowledge and health partner
      counseling for development and maintenance of healthy behaviors. This paper
      reports on the change in health profiles for over 90 traits, measured in 382
      participants over three visits in the 12 months following enrolment. Significant
      changes in the desired direction of improved health are observed for many traits
      related to cardiovascular health, including BMI, blood pressure, cholesterol, and
      arterial stiffness, as well as for summary measures of physical and mental
      health. The changes are most notable for individuals in the upper quartile of
      baseline risk, many of whom showed a positive correlated response across clinical
      categories. By contrast, individuals who start with more healthy profiles do not
      generally show significant improvements and only a modest impact of targeting
      specific health attributes was observed. Overall, the CHDWB model shows promise
      as an effective intervention particularly for individuals at high risk for
      cardiovascular disease. 

PMID- 25563460
TI  - Changes in weight bias and perceived employability following weight loss and
      gain.
AB  - BACKGROUND: The present weight stigma study examined whether attitudes toward and
      employability of a normal weight person can change after learning that the person
      had been obese. METHODS: Participants (N = 154) viewed an image of a normal
      weight woman and rated their impression of her. Next, participants rated their
      impression of her overweight image after learning how she had previously gained
      and subsequently lost weight. RESULTS: Participants rated the model far less
      favorably including perceived employability if they thought the once overweight
      model lost weight through surgery vs. diet and exercise. How the model initially
      gained the weight had little impact on participant ratings. CONCLUSIONS: Surgical
      weight loss had a significant impact on personality judgments. These negative
      views extended to hiring decisions.

PMID- 25563462
TI  - Argon laser-assisted treatment of benign eyelid lesions.
AB  - We investigated the treatment of benign eyelid lesions with argon laser as an
      alternative therapy to surgical excision. The charts of 73 patients with 95
      lesions treated with argon laser photocoagulation were reviewed retrospectively.
      In all patients, the procedure was performed for cosmetic reasons. The laser spot
      size ranged from 50 to 200 MUm, the power varied from 300 to 700 mW, and the
      exposure time ranged between 0.1 and 0.2 s. The lesions were mostly located on
      the upper eyelid (66%); the lid margin was involved in 30 cases. The mean follow
      up time was 7.2 +/- 3.5 months (range 3-15 months). A histopathological diagnosis
      was confirmed for 81 lesions (85.3%). All patients were satisfied with the
      cosmetic result. No intraoperative complications occurred, and none of the
      patients complained of pain during laser application. All wounds epithelialized
      in 3-4 weeks with skin that appeared normal. Hypopigmentation of the treated
      areas were observed in three cases. No recurrence occurred during the follow-up
      period. Argon laser-assisted benign eyelid tumor excision is a useful, cheap,
      accessible, and well-tolerated alternative to traditional surgery.

PMID- 25563463
TI  - What do we know about lipoprotein(a)?

PMID- 25563461
TI  - Targeted photodynamic therapy in head and neck squamous cell carcinoma: heading
      into the future.
AB  - The aim of this article is to give an insight into the future of photodynamic
      therapy (PDT) in head and neck squamous cell carcinoma (HNSCC). Through the
      combination of a photosensitizing agent with light and oxygen, PDT produces
      highly cytotoxic reactive oxygen species leading to selective tumor eradication.
      PDT is an attractive treatment for focal therapy of localized tumors, especially
      in the case of unresectable tumors. In HNSCC, over 1500 patients have been
      treated by PDT, and the majority of them responded quite favorably to this
      treatment. However, the non-negligible photosensitization of healthy tissue is a
      major limitation for the clinical application of PDT. Improvement in tumor
      selectivity is the main challenge that can be taken up by the use of a new
      generation of photosensitizing nanoparticles. Passive targeting, by using
      functionalised nanocarriers to target to overexpressed transmembrane receptors
      afford attractive solutions. To this day, epidermal growth factor receptor (EGFR)
      remains the only validated molecular target for HNSCC, and photosensitizer
      immunoconjugates to EGFR have been developed for the intracellular delivery of
      photosensitizing agents. Depending on coordinated research between biomarkers,
      specific ligands, and photosensitizers, similar approaches could be rapidly
      developed. In addition, some photosensitizers hold high fluorescence yield and
      therefore could emerge as theranostic agents. 

PMID- 25563464
TI  - Polymorphism rs7023923 and monocyte count in blood donors and coronary artery
      disease patients.
AB  - BACKGROUND: The importance of the role of monocytes in coronary artery disease
      (CAD) is well documented. An increased number of circulating monocytes is
      associated with higher incidence of CAD. Both environmental and genetic factors
      influence monocytosis. The latter have been extensively studied since the
      development of high-throughput genome-wide association studies. Several
      associations between polymorphisms and monocytosis were found among healthy
      individuals; the first example was rs7023923. The magnitude of the association of
      studied polymorphisms with the trait of interest is often confounded by
      environmental factors and may therefore differ between patient and healthy
      populations. It is very important to determine the magnitude of the association
      among patients to predict outcome of the disease, e.g. myocardial infarction.
      AIM: To determine whether the magnitude of association of rs7023923 with
      monocytosis, previously reported among healthy volunteers, is similar in patients
      in whom diagnosis of CAD was determined during elective coronarography. METHODS
      AND RESULTS: Leucocytosis and neutrophilocytosis were higher among patients with
      CAD, while thrombocytosis was lower. Monocyte count did not differ among the
      studied groups (p = 0.25). We confirmed the association of rs7023923 with
      monocytosis among healthy blood donors (p = 0.0156) but not among patients
      admitted for elective coronarography (p = 0.61). Inclusion of the age and sex of
      patients in the statistical model did not modify the results. CONCLUSIONS: Our
      data suggest that translation of the results of genetic association with the
      studied traits from healthy to patient population should be implemented with
      caution. It is possible that numerous environmental factors, which discriminate
      healthy volunteers from CAD patients, confound the magnitude of genetic
      associations and make interpretation of the data in patients less clear.

PMID- 25563465
TI  - The usefulness of cardiovascular magnetic resonance imaging in children with
      myocardial diseases.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) imaging is a clinically
      proven and reliable diagnostic method for the assessment of morphology, function,
      and characteristics of myocardial tissue in patients with myocardial diseases.
      The use of gadolinium contrast agents has created new diagnostic possibilities
      for tissue characterisation in patients with suspected or known cardiomyopathy,
      myocarditis, and cardiac tumours. AIM: To evaluate the usefulness of CMR in the
      diagnostic process in children with myocardial diseases and to compare the
      results of CMR and other non-invasive cardiovascular methods, including
      echocardiography. METHODS: The study included 112 children, with an average age
      of 12 +/- 4.64 years, with various forms of myocardial disease: 63 children with
      hypertrophic cardiomyopathy (HCM), 9 with suspected myocarditis, 5 with history
      of myocarditis, 4 with dilated cardiomyopathy (DCM), 9 with suspected
      arrhythmogenic right ventricular cardiomyopathy (ARVC), 6 with left ventricular
      non-compaction cardiomyopathy (LVNC), 9 with suspected restrictive cardiomyopathy
      (RCM) to be differentiated with constrictive pericarditis (CP), and 7 with
      cardiac tumours. RESULTS: CMR confirmed the echocardiographic diagnosis of HCM in
      92% of children and ruled it out in 8%, and in three children apical hypertrophy
      was found. CMR revealed the presence of myocardial fibrosis in 60% of patients
      with HCM. In 33% of children with clinically suspected myocarditis CMR confirmed
      this diagnosis, while in 44% of them DCM was recognised. Of the five children
      with a history of myocarditis, in one patient CMR performed 13 years after
      myocarditis revealed features of post-inflammatory DCM. In 75% of patients with
      the echocardiographic diagnosis of post-inflammatory DCM the result of CMR was
      consistent. CMR ruled out the presence of ARVC in 89% of children.
      Echocardiographic and CMR diagnosis of LVNC was consistent in 67% of children.
      CMR confirmed the clinical diagnosis of RCM in 63% of patients, and in one
      patient CP was recognised. CMR confirmed the presence of cardiac tumour in 57% of
      children and excluded it in 43% of patients. CONCLUSIONS: CMR is increasingly
      recognised as an important tool in the investigation of myocardial disease and
      should be part of routine clinical work-up. CMR provides an additional diagnostic
      technique to assess the presence or exclusion of an active myocarditis. In
      children with clinical and echocardiographic suspicion of LVNC, ARVC, RCM, CP,
      and cardiac tumours CMR can conclusively confirm the presence of the disease.

PMID- 25563466
TI  - Particularities of endothelial dysfunction in hypothyroid patients.
AB  - BACKGROUND: It is well known that hypothyroidism promotes the premature onset of
      subclinical atherosclerosis. This condition is defined by endothelial dysfunction
      (ED) and increased arterial stiffness (AS) and leads to augmentation of
      peripheral vascular resistance. AIM: To assess the presence and severity of ED
      and to follow its evolution under therapy in three groups of hypothyroid
      patients, we used three different noninvasive methods: carotidian intima-media
      thickness (IMT), flow mediated vasodilatation (FMD), and AS. METHODS: The study
      group consisted of 56 young, hypothyroid women without associated cardiovascular
      pathology or risk factors for atherosclerosis. We selected our patients in order
      to have normal IMT (< 0.9 mm) and assessed the basal diameter of the brachial
      artery and the alterations of FMD and of AS parameters: pulse wave velocity (PWV)
      and augmentation index (AIx). RESULTS: We found, in all patients, a reduced basal
      diameter of brachial artery, pathological patterns of FMD, and increased values
      of PWV and AIx, compared to controls, in relation with the severity of thyroid
      dysfunction. We documented an improvement of ED after therapy with L-thyroxin.
      CONCLUSIONS: ED, documented in hypothyroid patients by means of three
      noninvasively methods, was strongly related to the severity of thyroid disease.
      We detected, in all three subgroups, significant alterations of FMD and AS, even
      in the absence of structural changes, documented by a normal IMT. ED improved
      consistently after restoring the euthyroid state.

PMID- 25563467
TI  - Comparison between fragmented QRS and Q waves in myocardial scar detection using
      myocardial perfusion single photon emission computed tomography.
AB  - BACKGROUND: Accurate diagnosis of myocardial infarction (MI) is of paramount
      importance in patient management, which necessitates the development of efficient
      and accurate diagnostic methods. Q wave is not present in all patients with MI,
      and its prevalence is declining. Recently, fragmented QRS (fQRS) complex has been
      introduced as a marker of prior MI. AIM: To investigate diagnostic value of fQRS
      compared to Q wave. METHODS: We included 500 consecutive patients with known or
      suspected coronary artery disease who underwent two days of gated myocardial
      perfusion imaging using dipyridamole pharmacologic stress. Electrocardiogram
      (ECG) was evaluated to detect fQRS as well as Q-wave. Finally, subjects were
      compared in terms of ventricular perfusion and function indices. RESULTS: A total
      of 207 men and 269 women with mean age of 57.06 +/- 12 years were studied. ECG
      analysis showed that 14.3% of the patients had both fQRS and Q waves, 30.7% had
      fQRS, and 3.8% had Q waves. Fixed myocardial perfusion defect was noted in 22.3%
      of patients according to MPIs. Sensitivity, specificity, and positive and
      negative predictive values for myocardial scar detection were 78%, 65%, 39%, and
      91%, respectively, for fQRS and 61%, 94%, 76%, and 89%, respectively, for Q wave.
      CONCLUSIONS: Although fQRS had lower specificity compared to Q wave in the
      detection of myocardial scar, due to higher sensitivity and negative predictive
      value can be an invaluable diagnostic index. There is also an incremental value
      for fQRS in association with Q-wave in myocardial scar assessment.

PMID- 25563468
TI  - Tissue inhibitors of matrix metalloproteinases in serum are cardiac biomarkers in
      Emery-Dreifuss muscular dystrophy.
AB  - BACKGROUND: Tissue inhibitors of matrix metalloproteinases (TIMPs) are known to
      be involved in cardiovascular diseases. Hitherto, they have not been examined in
      dilated cardiomyopathy in the course of Emery-Dreifuss muscular dystrophy (EDMD).
      AIM: To define TIMPs in serum because they might help in defining cardiac
      dysfunction at the early cardiological stages of this disease and detect
      preclinical stages of cardiomyopathy. METHODS: Twenty-five EDMD patients
      connected with lamin A/C (AD-EDMD) or emerin (X-EDMD) deficiency and 20 healthy
      age-matched controls were examined. The serum levels of the tissue inhibitors
      TIMP-1, -2, -3 were quantified using the ELISA sandwich immunoassay procedure
      with appropriate antibodies. RESULTS: Serum levels of TIMP-1 were normal in
      autosomal AD-EDMD and increased in the majority of X-linked EDMD. The level of
      TIMP-2 was decreased in 25%/21% of AD-EDMD/X-EDMD cases. TIMP-3 serum level was
      significantly reduced in all the examined patients. Receiver operating curves
      indicated that in terms of sensitivity and specificity characteristics the
      performance of TIMP-3 (less that of TIMP-2) makes them the best markers of
      cardiac involvement among the examined TIMPs. CONCLUSIONS: Evidence shows that
      the levels of TIMP-3, and in some cases also TIMP-2, are decreased in EDMD. The
      decrease might be associated with an adverse effect on matrix metalloproteinases
      and remodelling of the myocardial matrix. The specific decrease of TIMP-3
      indicates that this biomarker might help in early detection of cardiac
      involvement in EDMD. Up-regulation of TIMP-1 in the majority of patients with X
      EDMD indicates increased myocardial extracellular matrix turnover, early onset of
      tissue remodelling, and may contribute to arrhythmia, frequently occurring in
      this form of the disease.

PMID- 25563469
TI  - Old markers, new approach to assessment of risk in heart failure.
AB  - BACKGROUND: Heart transplantation (HTx) is still the optimal treatment for
      refractory heart failure (HF). However, there is great disproportion between the
      number of donors and potential recipients. Several parameters are used in patient
      evaluation before HTx, but the qualification process still requires improvement.
      High-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) possess high prognostic value for patients with advanced HF.
      AIM: To assess the prognostic significance of NT-proBNP and hsCRP separately, as
      well as in combination, in a group of patients with advanced HF, considered for
      HTx. METHODS: Registry - 632 patients referred for HTx in Poland (2003-2007).
      Following proper treatment correction and routine clinical evaluation (i.e. mean
      New York Heart Association [NYHA] classification 3.2 +/- 0.6, heart rate 77 +/-
      15 bpm, systolic/diastolic blood pressure [SBP/DBP] 103/67 +/- 15/11 mm Hg, left
      ventricular ejection fraction [LVEF] 22 +/- 8%, serum Na+ 136 +/- 4 mmol/L, NT
      proBNP 3942 +/- 5637 pg/mL, hsCRP 9 +/- 22 mg/L levels, HFSS according to
      Aaronson 8 +/- 1, etc.) patients were qualified for HTx. Based on ROC analysis
      (cut-off points for NT-proBNP 2435 pg/mL and hsCRP 2.4 mg/L) subjects were
      stratified into four subgroups: (1) non-elevated hsCRP (-)/NT-proBNP (-) (n =
      179); (2) non-elevated hsCRP (-)/ /elevated NT-proBNP (+) (n = 92); (3) elevated
      hsCRP (+)/non-elevated NT-proBNP (-) (n = 159); and (4) elevated hsCRP (+)/ /NT
      proBNP (+) (n = 202). The end point was defined as death/urgent HTx. The mean
      follow-up period was 601 days. RESULTS: In univariate regression analysis we
      confirmed that classical risk factors were independent predictors of end point:
      NYHA (HR = 2.311; p < 0.0001), heart rate (HR = 1.016; p = 0.0009), SBP (HR =
      0.984; p = 0.0111), LVEF (HR = 0.951; p < 0.0001), serum Na+ (HR = 0.901; p <
      0.0001), NT-proBNP (HR = 1.004; p = 0.0159), and hsCRP (HR = 1.010; p = 0.0002);
      HFSS (HR = 0.557; p < 0.0001). Frequency-of-events analysis revealed that
      patients in the hsCRP (-)/ /NT-proBNP (-) subgroup presented with the best
      prognosis (13% of patients reached end point) followed by the hsCRP (-)/ /NT
      proBNP (+) subgroup, in which 24% of patients reached end point (Kaplan-Meier c2
      = 8.5319; p = 0.0035) and the hsCRP (+)/NT-proBNP (+) subgroup (c2 = 42.0413; p <
      0.0001), which was associated with the worst prognosis (39% of patients reached
      end point). CONCLUSIONS: The classical risk factors: NYHA class, heart rate, SBP,
      LVEF, HFSS, serum Na+, NT-proBNP, and hsCRP concentrations, proved to be valuable
      in the assessment of risk in advanced HF patients. However, concomitant
      evaluation of old markers: hsCRP and NT-proBNP, may become a good prognostic tool
      for identification of highest-risk patients among all referred for HTx. Such a
      new approach to risk stratification before HTx seems promising but requires
      further investigation.

PMID- 25563470
TI  - Analysis of the QRS morphology in lead V1 during 24-hour Holter electrocardiogram
      monitoring to evaluate function of a cardiac resynchronisation therapy device in
      patients with sinus rhythm: a pilot study.
AB  - BACKGROUND: Cardiac resynchronisation therapy (CRT) is an important advance in
      the treatment of chronic heart failure. The aim of CRT is biventricular capture
      in all beats. However, inadequate delivery of biventricular pacing is still seen
      in about 30% of patients with an implanted CRT device. Device interrogation is a
      routine approach to assess CRT delivery. However, some reports indicate that
      analysis of 24-h electrocardiogram (ECG) may provide additional and important
      information regarding CRT function. AIM: Assessment of the adequacy of CRT
      delivery based on device interrogation and analysis of QRS morphology during 24-h
      ECG recording in patients with preserved sinus rhythm (SR). METHODS: We analysed
      24-h Holter ECG recordings and data from device interrogation devices in 43
      patients with preserved SR (age 56 +/- 23 years, 9 women and 34 men). The
      obtained results were compared in an independent manner. Assessment of adequacy
      of CRT delivery by 24-h ECG was based on the occurrence of QRS variability,
      defined as a change in R wave amplitude in lead V1 by > 3 mm and/or change in QRS
      duration by > 40 ms and/or change in the R/S ratio. Adequate CRT delivery, i.e.
      complete resynchronisation, was defined as more than 95% of pacing without the
      defined QRS variability. RESULTS: Both methods allowed independent assessment of
      CRT delivery (p < 0.05 by the Fisher's exact test). In multivariate analysis,
      factors that were independently associated with incomplete resynchronisation
      included ventricular arrhythmias (each 100 ventricular beats per day increased
      the risk of incomplete resynchronisation 1.14-fold; confidence interval [CI]
      1.036-1.25, p = 0.007), maximum heart rate (HR) (each increase by 10 bpm
      increased the risk 3.3-fold; CI 1.36-7.9, p = 0.008), QRS duration at the minimum
      HR (each increase by 10 ms increased the risk 1.74-fold; CI 1.075-2.8, p =
      0.024), and the programmed atrioventricular delay (each increase by 10 ms
      increased the risk 2.15-fold, CI 1.18-3.9, p = 0.013). CONCLUSIONS: In patients
      with preserved SR, device interrogation and evaluation of 24-h ECG are
      complementary methods to evaluate adequate CRT delivery. Therefore, both methods
      should be taken into account when assessing CRT function.

PMID- 25563471
TI  - In-hospital outcomes and mortality in octogenarians after percutaneous coronary
      intervention.
AB  - BACKGROUND: There is systematic growth in the number of number of elderly
      patients treated with percutaneous coronary intervention (PCI); however, little
      is known about PCI results in the very elderly (long-lived) patients aged 85
      years and above. AIM: To assess the demographic, clinical, and angiographic
      findings in patients aged > 85 years (GER), undergoing PCI, compared with younger
      patients treated in the year 2012. METHODS: This was a single centre
      retrospective study based on a consecutive group of 920 patients with coronary
      disease (stable and acute coronary syndrome [ACS]). Patients were divided into
      two groups: GER aged 85 years and over (n = 82) and controls (CG) below 85 years
      (n = 838). RESULTS: The mean age in the GER group was 88.6 vs. 66.7 years in the
      CG. There were more females in the GER group (57% vs. 29%) than in the CG (p <
      0.001). The indication for PCI was mainly ACS in GER (65%) vs. CG (50%) including
      ST segment elevation myocardial infarction (STEMI) 30% vs. 29% (p = NS), ACS non
      STEMI 35% vs. 20% (p = 0.01). GER patients had more comorbidities and more
      advanced multivessel coronary artery disease. The ratio of procedural success was
      lower in GER compared to CG. The incidence of in-hospital death was higher in GER
      (4.8%) compared to CG (0.83%); the most common complication in GER group was
      contrast-induced nephropathy (18.2% vs. 6.2%). Major adverse cardiovascular
      events were significantly more frequent in GER patients with ACS compared to CG
      patients with the same diagnosis. CONCLUSIONS: Patients > 85 years old,
      especially with ACS undergoing PCI, are at greater risk of in-hospital
      complications, especially contrast-induced nephropathy and procedural
      complications, compared to younger patients.

PMID- 25563472
TI  - Exercise-induced mobilisation of endothelial progenitor cells in patients with
      premature coronary heart disease.
AB  - BACKGROUND: Endothelial progenitor cells (EPC) derive from bone marrow and
      participate in both endothelial regeneration and development of new blood
      vessels. EPC also play a role in the atherosclerotic process, and their number
      correlates negatively with the presence of classical risk factors. AIM: To
      evaluate circulating EPC count and their exercise-induced mobilisation in
      patients with premature coronary artery disease (CAD). METHODS: The study group
      included 60 patients with stable CAD diagnosed before 45 years of age. The
      control group consisted of 33 healthy age- and gender-matched volunteers. Venous
      blood was sampled 3 times in order to assess circulating EPC count immediately
      before an exercise test (EPC 0) and at 15 min (EPC 15) and 60 min (EPC 60) after
      the exercise test. RESULTS: Circulating EPC count in the study group at rest and
      at 15 min after exercise was comparable (2.1 vs. 2.1 cell/MUL, p = 0.35) and
      increased significantly at 60 min after exercise in comparison to resting values
      (2.1 vs. 3.2 cell/MUL, p < 0.00001). In the control group, circulating EPC count
      increased significantly at 15 min after exercise (2.0 vs. 3.5 cell/MUL, p <
      0.0001) but later decreased at 60 min after exercise, although it remained
      greater than at rest (2.7 vs. 2.0 cell/MUL, p < 0.0002). Circulating EPC count at
      rest and at 60 min after exercise was comparable in the two groups (2.1 vs. 2.0
      cell/MUL, p = 0.96; and 3.2 vs. 2.7 cell/MUL, p = 0.13, respectively) but it was
      significantly lower in the study group compared to the control group at 15 min
      after exercise (2.1 vs. 3.5 cell/MUL, p < 0.00001). Circulating EPC count at rest
      and at 15 min after exercise did not correlate with the number of stenosed
      coronary arteries but at 60 min after exercise it was greater in patients with
      one-vessel disease compared to those with two- or three-vessel disease (4.2 vs.
      3.4 cell/MUL, p = 0.01; and 4.2 vs. 2.3 cell/MUL, p = 0.00003). However, no
      difference in circulating EPC count was seen at 60 min after exercise between
      patients with two- or three-vessel disease (3.4 vs. 2.3 cell/MUL, p = 0.3).
      CONCLUSIONS: 1. Circulating EPC count at rest is comparable between subjects with
      premature atherosclerosis and healthy volunteers. 2. A single bout of physical
      exercise causes a significant increase in circulating EPC count in both groups,
      but the dynamics of exercise-induced EPC mobilisation is different, with delayed
      exercise-induced EPC mobilisation in subjects with premature CAD. 3. The extent
      of atherosclerotic coronary lesions does not influence circulating EPC count at
      rest.

PMID- 25563473
TI  - The importance of electrocardiographic findings in the diagnosis of atrial septal
      defect.
AB  - BACKGROUND: Atrial septal defect (ASD) is the most frequent heart defect observed
      in adulthood. Although it is usually non-symptomatic, it may result in heart
      failure, arrhythmic complications, and paradoxical embolism-related morbidity or
      mortality if the diagnosis is late. AIM: This study was planned in order to
      investigate the importance of electrocardiographic findings in the diagnosis of
      ASD. METHODS: Sixty-one patients with a diagnosis of ASD and 66 healthy
      volunteers without cardiac disease were enrolled in the study.
      Electrocardiographs (ECG) were performed on all patients to investigate the
      presence of right bundle branch block (RBBB), incomplete RBBB, defective T wave
      (DTW), and notch finding in the R wave of inferior derivations (crochetage R
      wave). ASD types and diameters were determined via transthoracic and
      transoesophageal echocardiography. RESULTS: It was determined that incomplete
      RBBB (56% vs. 5%), DTW (48% vs. 3%), and R wave crochetage (57% vs. 8%) in
      inferior derivations were more frequent in ASD patients compared to the control
      group patients. The specificity of the defined ECG findings in the diagnosis of
      ASD were 95%, 97%, and 92%, respectively. No correlation was detected between the
      ASD diameter and incomplete RBBB, whereas significant correlation was observed
      between the ASD diameter and the presence of crochetage R wave (17.5 +/- 4.0 mm
      in patients with crochetage R wave, and 20.9 +/- 8.2 mm in patients without
      crochetage R wave, p = 0.057). CONCLUSIONS: Detection of RBBB, DTW, and
      crochetage R wave in superficial ECG may contribute to early detection in
      patients with ASD.

PMID- 25563475
TI  - Airborne single particle mass spectrometers (SPLAT II & miniSPLAT) and new
      software for data visualization and analysis in a geo-spatial context.
AB  - Understanding the effect of aerosols on climate requires knowledge of the size
      and chemical composition of individual aerosol particles-two fundamental
      properties that determine an aerosol's optical properties and ability to serve as
      cloud condensation or ice nuclei. Here we present our aircraft-compatible single
      particle mass spectrometers, SPLAT II and its new, miniaturized version,
      miniSPLAT that measure in-situ and in real-time the size and chemical composition
      of individual aerosol particles with extremely high sensitivity, temporal
      resolution, and sizing precision on the order of a monolayer. Although
      miniSPLAT's size, weight, and power consumption are significantly smaller, its
      performance is on par with SPLAT II. Both instruments operate in dual data
      acquisition mode to measure, in addition to single particle size and composition,
      particle number concentrations, size distributions, density, and asphericity with
      high temporal resolution. We also present ND-Scope, our newly developed
      interactive visual analytics software package. ND-Scope is designed to explore
      and visualize the vast amount of complex, multidimensional data acquired by our
      single particle mass spectrometers, along with other aerosol and cloud
      characterization instruments on-board aircraft. We demonstrate that ND-Scope
      makes it possible to visualize the relationships between different observables
      and to view the data in a geo-spatial context, using the interactive and fully
      coupled Google Earth and Parallel Coordinates displays. Here we illustrate the
      utility of ND-Scope to visualize the spatial distribution of atmospheric
      particles of different compositions, and explore the relationship between
      individual particle compositions and their activity as cloud condensation nuclei.

PMID- 25563476
TI  - Maternal intake of fatty acids and their food sources during lactation and the
      risk of preclinical and clinical type 1 diabetes in the offspring.
AB  - AIMS: We examined maternal dietary intake of fatty acids and foods which are
      sources of fatty acids during lactation and whether they are associated with the
      risk of preclinical and clinical type 1 diabetes in the offspring. METHODS: The
      subjects comprised a cohort of 2,939 mother-child pairs from the prospective Type
      1 Diabetes Prediction and Prevention Study. Composition of maternal diet during
      the third month of lactation was assessed by a validated food frequency
      questionnaire. Among the children with HLA-conferred susceptibility to type 1
      diabetes, 172 developed preclinical and 81 clinical diabetes. Average follow-up
      for preclinical type 1 diabetes was 7.5 years (range 0.2-14.0 years) and for
      clinical type 1 diabetes 7.7 years (0.2-14.0 years). RESULTS: Maternal intake of
      fatty acids during lactation was not associated with the risk of type 1 diabetes
      in the offspring. After adjusting for putative confounders, maternal total
      consumption of red meat and meat products during lactation was associated both
      with increased risk for preclinical [hazard ratio (HR) 1.19, 95 % CI 1.02-1.40, p
      = 0.038] and clinical type 1 diabetes (HR 1.27, 95 % CI 1.06-1.52, p = 0.025). In
      particular, consumption of processed meat products showed an association with
      increased risk for type 1 diabetes (HR 1.23, 95 % CI 1.02-1.48, p = 0.045).
      Maternal use of vegetable oils was associated with increased risk for preclinical
      type 1 diabetes (HR 1.21, 95 % CI 1.03-1.41, p = 0.023). CONCLUSIONS: Maternal
      consumption of red meat, especially processed meat, during lactation may increase
      the risk of type 1 diabetes.

PMID- 25563477
TI  - Bilateral lower limbs edema with "wooden" character induced by insulin glargine
      treatment.

PMID- 25563474
TI  - Viral vectors encoding endomorphins and serine histogranin attenuate neuropathic
      pain symptoms after spinal cord injury in rats.
AB  - BACKGROUND: The treatment of spinal cord injury (SCI)-induced neuropathic pain
      presents a challenging healthcare problem. The lack of available robust
      pharmacological treatments underscores the need for novel therapeutic methods and
      approaches. Due to the complex character of neuropathic pain following SCI,
      therapies targeting multiple mechanisms may be a better choice for obtaining
      sufficient long-term pain relief. Previous studies in our lab showed analgesic
      effects using combinations of an NMDA antagonist peptide [Ser1]histogranin (SHG),
      and the mu-opioid peptides endomorphins (EMs), in several pain models. As an
      alternative to drug therapy, this study evaluated the analgesic potential of
      these peptides when delivered via gene therapy. RESULTS: Lentiviruses encoding
      SHG and EM-1 and EM-2 were intraspinally injected, either singly or in
      combination, into rats with clip compression SCI 2 weeks following injury.
      Treated animals showed significant reduction in mechanical and thermal
      hypersensitivity, compared to control groups injected with GFP vector only. The
      antinociceptive effects of individually injected components were modest, but the
      combination of EMs and SHG produced robust and sustained antinociception. The
      onset of the analgesic effects was observed between 1-5 weeks post-injection and
      sustained without decrement for at least 7 weeks. No adverse effects on locomotor
      function were observed. The involvement of SHG and EMs in the observed
      antinociception was confirmed by pharmacologic inhibition using intrathecal
      injection of either the opioid antagonist naloxone or an anti-SHG antibody.
      Immunohistochemical analysis showed the presence of SHG and EMs in the spinal
      cord of treated animals, and immunodot-blot analysis of CSF confirmed the
      presence of these peptides in injected animals. In a separate group of rats,
      delayed injection of viral vectors was performed in order to mimic a more likely
      clinical scenario. Comparable and sustained antinociceptive effects were observed
      in these animals using the SHG-EMs combination vectors compared to the group with
      early intervention. CONCLUSIONS: Findings from this study support the potential
      for direct gene therapy to provide a robust and sustained alleviation of chronic
      neuropathic pain following SCI. The combination strategy utilizing potent mu
      opioid peptides with a naturally-derived NMDA antagonist may produce additive or
      synergistic analgesic effects without the tolerance development for long-term
      management of persistent pain.

PMID- 25563479
TI  - Calcitonin gene-related peptide stimulates proliferation and osteogenic
      differentiation of osteoporotic rat-derived bone mesenchymal stem cells.
AB  - Osteoporosis, a systemic bone disorder, is prevalent in postmenopausal woman.
      Bone mesenchymal stem cells (BMSCs), precursors of osteogenic cells, may
      contribute to prevention or treatment of bone frustrate in osteoporosis.
      Recently, two studies suggested a role of calcitonin gene-related peptide (CGRP)
      in promoting osteogenesis of BMSCs under physiological conditions. However, the
      role of CGRP on BMSCs, which are derived from osteoporotic tissues, is unclear.
      Here, we investigated the role of CGRP on BMSCs isolated from female osteoporotic
      rats. Data showed that CGRP stimulated cell proliferation and inhibited cell
      apoptosis for short-term culture of BMSCs. Instead, CGRP induced BMSCs
      differentiation into the osteoblasts and promoted formation of calcified nodules
      after long-term culture. Moreover, CGRP gradually up-regulated expression levels
      of osteoporotic differentiation-related genes including alkaline phosphatase,
      Collagen type I, Bmp2, Osteonectin, and Runx2 during osteogenic differentiation.
      In conclusion, CGRP promoted proliferation and induced osteogenic differentiation
      and mineralization during female osteoporotic rat-derived BMSC differentiation.
      These findings support a potential role of CGRP on the prevention or treatment of
      osteoporotic fracture. 

PMID- 25563478
TI  - Atazanavir improves cardiometabolic measures but not vascular function in
      patients with long-standing type 1 diabetes mellitus.
AB  - AIMS: Vascular disease is the leading cause of morbidity and mortality in type 1
      diabetes mellitus (T1DM). We previously demonstrated that patients with T1DM have
      impaired endothelial function, a forme fruste of atherosclerosis, as a result of
      increased oxidative stress. Bilirubin has emerged as a potent endogenous
      antioxidant with higher concentrations associated with lower rates of myocardial
      infarction and stroke. METHODS: We tested the hypothesis that increasing
      endogenous bilirubin using atazanavir would improve cardiometabolic risk factors
      and vascular function in patients with T1DM to determine whether targeting
      bilirubin may be a novel therapeutic approach to reduce cardiovascular disease
      risk in this population. In this single-arm, open-label study, we evaluated blood
      pressure, lipid profile, and conduit artery function in fifteen subjects (mean
      age 45 +/- 9 years) with T1DM following a 4-day treatment with atazanavir.
      RESULTS: As anticipated, atazanavir significantly increased both serum total
      bilirubin levels (p < 0.0001) and plasma total antioxidant capacity (p < 0.0001).
      Reductions in total cholesterol (p = 0.04), LDL cholesterol (p = 0.04), and mean
      arterial pressure (p = 0.04) were also observed following atazanavir treatment.
      No changes were seen in either flow-mediated endothelium-dependent (p = 0.92) or
      nitroglycerine-mediated endothelium-independent (p = 0.68) vasodilation, measured
      by high-resolution B-mode ultrasonography at baseline and post-treatment.
      CONCLUSION: Increasing serum bilirubin levels with atazanavir in subjects with
      T1DM over 4 days favorably reduces LDL and blood pressure but is not associated
      with improvements in endothelial function of conduit arteries.

PMID- 25563482
TI  - Morphometric study of the medial orbital wall emphasizing the ethmoidal foramina.
AB  - PURPOSE: Ethmoidal foramina on the medial orbital wall show a higher incidence of
      variation. Surgeons performing endonasal, anterior cranial fossa and medial
      orbital wall surgeries must be aware of these variations as they are a source of
      hemorrhage and also serve as landmark in proximity to the orbital apex. AIM: The
      present study aims to describe the morphometric distances of various ethmoidal
      foramina between anterior lacrimal crest to optic canal in south Indian dry human
      skulls. MATERIALS AND METHOD: The study was done on 44 adult dry human skulls.
      The occurrence of Ethmoidal foramina was noted by direct inspection. The distance
      of Ethmoidal foramina from anterior lacrimal crest to optic canal was measured
      with the help of ruler, probe and magnifying glass. RESULTS: The Posterior
      ethmoidal foramina were found in all 44 skulls bilaterally. Middle ethmoidal
      foramen was present in 12 and 13 skulls on right and left, respectively. Anterior
      ethmoidal foramen was found in 38 and 37 skulls on right and left, respectively.
      The distance between anterior lacrimal crest (ALC) and posterior lacrimal crest
      (PLC) was in the range of 3-8 mm and that of ALC to anterior ethmoidal foramen
      was in the range of 24-30 mm. The range of distance between anterior ethmoidal
      foramen to posterior ethmoidal foramen was 9-17 mm and that between posterior
      ethmoidal foramen to optic canal was 5-13 mm. CONCLUSION: These observations
      would help to predict the anatomical variations in the position of ethmoidal
      foramina with respect to anterior and posterior lacrimal crest and ensure the
      safe and precise performance of medial orbital wall surgeries to avoid injuries
      to the important neurovascular bundles passing through various foramina and
      fissures.

PMID- 25563480
TI  - IL-12 could induce monocytic tumor cells directional differentiation.
AB  - Interleukin-12 (IL-12), a member of interleukin family, plays a critical role in
      immune responses and anti-tumor activity. In this study, the effects of IL-12 on
      monocytic tumor cell lines differentiation to macrophagocyte and its likely
      mechanism was investigated. We examined the differentiation markers,
      morphological and functional changes, and possible mechanism in IL-12-treated THP
      1 and U937 cells. It was found that IL-12 could up-regulated macrophage surface
      marker CD68 and CD11b expression in a time-dependent manner. Morphologically,
      after IL-12 treatment, THP-1 and U937 cells became round or irregular shape, even
      stretched many cell membrane protuberances; some cell nuclei became fuzzy or
      completely disappeared, and the chromatin appeared dense and cordlike.
      Furthermore, IL-12-induced monocytic tumor cell differentiation was accompanied
      by the growth arrest with G1-phase accumulation and S-phase reduction; apoptosis
      increased with anti-apoptosis protein Bcl-2 down-expression and pro-apoptosis
      protein Fas up-regulation, and enhanced phagocytosis function. The IL-12-induced
      macrophage differentiation of THP-1 and U937 cells was associated with the up
      regulation of c-fms expression and the CSF-1R Tyr 809 site phosphorylation. These
      findings have revealed that IL-12 could induce monocytic tumor cells directional
      differentiation into macrophage-like cells, and its mechanism is possible
      connected with the up-regulation of c-fms expression and the phosphorylation of
      CSF-1R Tyr-809 site. 

PMID- 25563483
TI  - Hospital readmission rates and emergency department visits for mental health and
      substance abuse conditions.
AB  - Community hospital stays in 12 states during 2008-2009 were analyzed to determine
      predictors of 12-month hospital readmission and emergency department (EDs)
      revisits among persons with a mental health or substance abuse diagnosis.
      Probabilities of hospital readmission and of ED revisits were modeled as
      functions of patient demographics, insurance type, number of prior-year hospital
      stays, diagnoses and other characteristics of the initial stay, and hospital
      characteristics. Alcohol or drug dependence, dementias, psychotic disorders,
      autism, impulse control disorders, and personality disorders were most strongly
      associated with future inpatient admission or ED revisits within 12 months of
      initial encounter. Insurance type, including uninsured status, were highly
      significant (p<.01) predictors of both readmission and ED revisits.

PMID- 25563481
TI  - Vitamin D deficiency decreases survival of bacterial meningoencephalitis in mice.
AB  - BACKGROUND: Meningoencephalitis caused by Escherichia coli is associated with
      high rates of mortality and risk of neurological sequelae in newborns and infants
      and in older or immunocompromised adults. A high prevalence of neurological
      disorders has been observed in geriatric populations at risk of hypovitaminosis
      D. METHODS: In vivo, we studied the effects of vitamin D3 on survival and the
      host's immune response in experimental bacterial meningoencephalitis in mice
      after intracerebral E. coli infection. To produce different systemic vitamin D3
      concentrations, mice received a low, standard, or high dietary vitamin D3
      supplementation. Bacterial titers in blood, spleen, and brain homogenates were
      determined. Leukocyte infiltration was assessed by histological scores, and
      tissue cytokine or chemokine concentrations were measured. RESULTS: Mice fed a
      diet with low vitamin D3 concentration died earlier than control animals after
      intracerebral infection. Vitamin D deficiency did not inhibit leukocyte
      recruitment into the subarachnoid space and did not lead to an increased density
      of bacteria in blood, spleen, or brain homogenates. The release of
      proinflammatory interleukin (IL)-6 was decreased and the release of anti
      inflammatory IL-10 was increased in mice fed a diet with high vitamin D3
      supplementation. CONCLUSION: Our observations suggest a detrimental role of
      vitamin D deficiency in bacterial central nervous system infections. Vitamin D
      may exert immune regulatory functions.

PMID- 25563484
TI  - Effects of Home Visit Intervention on Re-hospitalization Rates in Psychiatric
      Patients.
AB  - To examine the home visit intervention (HoVI) effects on the re-hospitalization
      rate and medical costs in patients with schizophrenia or other psychiatric
      disorders. The subjects who received more than 3 HoVIs were defined as the HoVI
      group, whereas the subjects who received equal to or less than 3 HoVIs were
      defined as the HoVI < 4 group; the subjects who had never received an HoVI were
      defined as the non-HoVI group. Differences in the re-hospitalization rates and
      National Health Insurance (NHI) costs among the three groups were examined. The
      re-hospitalization rate of the HoVI group was significantly lower than that of
      the non-HoVI group. The hospitalization days and the NHI costs of the HoVI group
      were also lower than those of the non-HoVI group. However, the HoVI < 4 group was
      not different than the non-HoVI group regarding the re-hospitalization rate or
      the hospitalization days. The re-hospitalization rate was significantly higher
      before compared with after the HoVIs. The NHI costs were significantly higher
      before compared with after the HoVIs. HoVIs (More than 3 HoVIs) produced a lower
      re-hospitalization rate, number of hospitalization days, and NHI costs in
      patients who received care through the Home Visit. Project to strengthen the
      Community Rehabilitation Program.

PMID- 25563485
TI  - The Role of Gender and Income in Predicting Barriers to Mental Health Care in
      Canada.
AB  - There have been traditionally low rates of health care utilization by persons
      with mental health issues in developed countries such as Canada due to barriers
      that discourage health care service use such as waitlists, long distances to
      health services, and stigma that can be associated with seeking help for mental
      health issues. This project examined barriers to mental health care using data
      from the Canadian Community Health Survey (N = 4,134) to understand gender and
      income-related disparities in access to mental health care services. Data were
      modeled using logistic regression to determine whether gender and household
      income predicted experiencing barriers to care. There were significant variations
      in the barriers to care reported by gender and income. Both men and women from
      low-income (<$29,999) households were significantly more likely to report all
      types of barriers to care. Men were much more likely to report 'acceptability'
      barriers to care that related to their perceptions of mental health issues and
      usefulness of health care services, whereas women were much more likely to report
      availability or accessibility issues such as a lack of transportation or
      childcare. The findings of this study demonstrate that despite universal health
      insurance, there are significant inequities in access to mental health care for
      low-income Canadians and differences in the types of barriers to care experienced
      by gender.

PMID- 25563486
TI  - Changing Social Networks Among Homeless Individuals: A Prospective Evaluation of
      a Job- and Life-Skills Training Program.
AB  - Social networks play important roles in mental and physical health among the
      general population. Building healthier social networks might contribute to the
      development of self-sufficiency among people struggling to overcome homelessness
      and substance use disorders. In this study of homeless adults completing a job-
      and life-skills program (i.e., the Moving Ahead Program at St. Francis House,
      Boston), we prospectively examined changes in social network quality, size, and
      composition. Among the sample of participants (n = 150), we observed positive
      changes in social network quality over time. However, social network size and
      composition did not change among the full sample. The subset of participants who
      reported abstaining from alcohol during the months before starting the program
      reported healthy changes in their social networks; specifically, while completing
      the program, they re-structured their social networks such that fewer members of
      their network used alcohol to intoxication. We discuss practical implications of
      these findings.

PMID- 25563489
TI  - Mammary lineage tracing: the coming of age.
AB  - Identification and characterization of the normal epithelial lineages in the
      mammary gland is a fundamental step in understanding both development and
      cellular origin of cancer. In contrast to other tissues where lineage tracing has
      been widely accepted as a method of choice for dissecting the stem cell
      hierarchy, mammary gland has long remained a challenge due to its unique
      developmental and topological features. Recent advances in high-resolution single
      cell imaging, combined with the use of inducible Cre-recombinase and in situ cell
      ablation, have provided unprecedented insight into mammary epithelial cell
      composition and function. Here, we briefly summarize and compare different
      mammary gland lineage tracing strategies, examine associated caveats and discuss
      future challenges and opportunities. 

PMID- 25563488
TI  - Interactions between cancer cells and normal cells via miRNAs in extracellular
      vesicles.
AB  - MicroRNAs (miRNAs) exhibit many functions in biological activities. Recent
      studies have shown that miRNAs exist outside cells and are transferred between
      cells. Extracellular miRNAs are protected from ribonucleases found in body fluids
      through binding to specific proteins or by being encapsulated in lipid bilayer
      vesicles. Here, we review the mechanisms of the secretion and uptake as well as
      the functions of extracellular miRNAs, particularly those encapsulated in
      extracellular vesicles. Extracellular vesicles are related to cancer progression,
      and some miRNAs in extracellular vesicles are associated with cancer cells. We
      describe the transfer of cancer-related miRNAs between cancer cells and non
      cancerous cells. Finally, we discuss the anticipated applications of miRNAs
      present in extracellular vesicles in diagnostics and therapeutics.

PMID- 25563487
TI  - Circadian clocks in rat skin and dermal fibroblasts: differential effects of
      aging, temperature and melatonin.
AB  - As a peripheral tissue localized at the interface between internal and external
      environments, skin performs functions which are critical for the preservation of
      body homeostasis, in coordination with environmental changes. Some of these
      functions undergo daily variations, such as temperature or water loss, suggesting
      the presence of time-keeping mechanisms. Rhythmic functions are controlled by a
      network of circadian oscillators present virtually in every cell and coordinated
      by the central clock located in the suprachiasmatic nuclei. At the molecular
      level, circadian rhythms are generated by conserved transcriptional-translational
      feedback loops involving several clock genes, among which Per1 and Per2 play a
      central role. Here we characterize clock activity in skin of the transgenic Per1
      luciferase rat during postnatal development and adulthood, by real-time recording
      of bioluminescence in explants and primary dermal fibroblasts, and report marked
      transformation in circadian properties, from early life to aging. Using primary
      dermal fibroblast cultures we provide evidence that melatonin treatment phase
      dependently increases the amplitude of circadian oscillations and that ambient
      temperature impacts on their period, with slight overcompensation. Together,
      these findings demonstrate that skin contains a self-sustained circadian clock
      undergoing age-dependent changes. Dermal fibroblasts, one of the major skin cell
      types, also exhibit robust, yet specific, circadian rhythmicity which can be fine
      tuned by both internal (melatonin) and external (temperature) factors. 

PMID- 25563490
TI  - Morphology and immunophenotype of canine cutaneous histiocytic tumours with
      particular emphasis on diagnostic application.
AB  - This study evaluated the morphology and immunohistochemistry of 85 canine
      cutaneous histiocytic tumours. The tumours were classified morphologically as
      either canine cutaneous histiocytomas (71 tumours) or canine cutaneous
      histiocytic sarcomas (14 tumours). The immunohistochemical analysis was conducted
      on paraffin sections using an antibody panel (against MHCII, CD18, CD79alphacy,
      CD3 and E-cadherin). Histochemical staining with toluidine blue and Gomori silver
      impregnation was also performed. A follow-up was conducted via surveys. The
      histiocytic origin of the tumour cells was confirmed in 65 of the canine
      cutaneous histiocytomas and in 4 of the canine cutaneous histiocytic sarcomas.
      The tumours that had been misdiagnosed as canine cutaneous histiocytomas included
      plasmacytomas, epitheliotropic T-cell lymphomas and undetermined entities. The
      tumours misdiagnosed as canine cutaneous histiocytic sarcomas included
      plasmacytomas and non-epitheliotropic T-cell lymphomas, but the majority of them
      remained undetermined. The canine cutaneous histiocytomas showed MHCII, CD18 and
      E-cadherin expression, but in several of the tumours, the expression of CD18 or E
      cadherin was confirmed in only a small percentage of the tumour cells. The
      regressing canine cutaneous histiocytomas showed increased T- and B-lymphocyte
      infiltration, a decreased mitotic index, transport of the MHCII molecules from
      the cytoplasm to the cell membrane and loss of E-cadherin expression in the
      tumour cells. The canine cutaneous histiocytic sarcomas showed both high
      morphological diversity and expression of MHCII and CD18. Two of the evaluated
      histiocytic sarcomas also showed expression of E-cadherin. In conclusion,
      immunohistochemistry, including analysis of MHCII, CD18 and the lymphocytic
      markers CD3 and CD79, should be performed for the diagnosis of canine cutaneous
      histiocytic tumours. The expression of E-cadherin in canine cutaneous histiocytic
      sarcomas suggests an origin of the tumour cells among Langerhans cells. 

PMID- 25563491
TI  - Histone storage and deposition in the early Drosophila embryo.
AB  - Drosophila development initiates with the formation of a diploid zygote followed
      by the rapid division of embryonic nuclei. This syncytial phase of development
      occurs almost entirely under maternal control and ends when the blastoderm embryo
      cellularizes and activates its zygotic genome. The biosynthesis and storage of
      histones in quantity sufficient for chromatin assembly of several thousands of
      genome copies represent a unique challenge for the developing embryo. In this
      article, we have reviewed our current understanding of the mechanisms involved in
      the production, storage, and deposition of histones in the fertilized egg and
      during the exponential amplification of cleavage nuclei. 

PMID- 25563492
TI  - Inhibition of heat shock protein 90 suppresses squamous carcinogenic progression
      in a mouse model of esophageal cancer.
AB  - PURPOSE: Heat shock protein 90 (Hsp90), a potential therapeutic target, has been
      widely recognized in vitro and in vivo in immunodeficient mice. Here, we aimed to
      evaluate the role of Hsp90 in an immunocompetent mouse model of esophageal
      squamous cell cancer (ESCC). METHODS: The carcinogen 4-nitroquinoline 1-oxide
      (4NQO) was used to induce ESCC in C57BL/6 mice. Cancer progression was analyzed
      through observation of appearance, hematoxylin-eosin staining,
      immunohistochemical detection, and terminal dUTP nick-end labeling analysis.
      RESULTS: 4NQO led to the progressive appearance of preneoplastic and tumoral
      lesions in the esophagus, with 100 % incidence of ESCC in situ occurring only
      after 16 weeks of carcinogen exposure. Most of these lesions evolved
      spontaneously into highly invasive ESCC even after 4NQO withdrawal (weeks 16-22).
      Interestingly, there was marked upregulation of Hsp90 and its client proteins in
      tumoral lesions at 22 weeks. Hsp90 inhibition by intraperitoneal injection of SNX
      2112 over the following 2 weeks downregulated AKT and cyclin D1 expression,
      leading to significant reduction in tumor incidence and prevention of ESCC
      progression. Moreover, SNX-2112 treatment decreased proliferating cell nuclear
      antigen expression and increased the number of apoptotic cells in ESCC tissues.
      CONCLUSIONS: Our in vivo findings support the contribution of Hsp90 to ESCC
      progression, which was achieved by stimulating apoptosis and inhibition of cell
      proliferation, and provide a strong rationale for further evaluation of Hsp90
      inhibitors for treating ESCC.

PMID- 25563493
TI  - Cervical cancer stem cells: opportunities and challenges.
AB  - INTRODUCTION: Cervical cancer remains a leading cause of cancer-related deaths in
      women in spite of screening and vaccination programs. The current treatment
      strategies including chemotherapy and surgery could only prolong the patient's
      survival rather than provide a permanent cure. In case of advanced cervical
      cancer, radical surgery remains the only option which not only affects the child
      bearing ability of the patient, but also comes with a continual risk of
      recurrence of the disease. Hence, there is a need to develop innovative
      therapeutics. The cancer stem cell hypothesis states that a tumor has a
      hierarchical cellular structure in which only a small subpopulation, referred to
      as cancer stem cells (CSCs), is capable of tumorigenesis. The CSCs possess the
      stem-like properties of self-renewal and can differentiate into non-stem tumor
      cells. RESULTS: A large number of studies suggest that CSCs are resistant to the
      conventional therapies used for cancer treatment. These therapies rather enrich
      the proportion of CSCs in the tumor by eliminating non-stem tumor cells, thereby
      causing enhanced drug resistance resulting in relapse of the disease. This makes
      CSCs as the most likely targets for therapeutic intervention. Also, the increase
      in the proportion of CSCs in patient samples is associated with poor survival
      rate, thus highlighting their potential role as prognostic biomarker. CONCLUSION:
      The CSCs have been identified and characterized in cervical cancer cell lines,
      but there are hardly any reports of CSCs in cervical cancer patient samples. This
      review highlights the current status of research on cervical CSCs, their clinical
      significance and the challenges in the field.

PMID- 25563494
TI  - Three CCT domain-containing genes were identified to regulate heading date by
      candidate gene-based association mapping and transformation in rice.
AB  - CCT domain-containing genes generally control flowering in plants. Currently,
      only six of the 41 CCT family genes have been confirmed to control flowering in
      rice. To efficiently identify more heading date-related genes from the CCT
      family, we compared the positions of heading date QTLs and CCT genes and found
      that 25 CCT family genes were located in the QTL regions. Association mapping
      showed that a total of 19 CCT family genes were associated with the heading date.
      Five of the seven associated genes within QTL regions and two of four associated
      genes outside of the QTL regions were confirmed to regulate heading date by
      transformation. None of the seven non-associated genes outside of the QTL regions
      regulates heading date. Obviously, combination of candidate gene-based
      association mapping with linkage analysis could improve the identification of
      functional genes. Three novel CCT family genes, including one non-associated
      (OsCCT01) and two associated genes (OsCCT11 and OsCCT19) regulated the heading
      date. The overexpression of OsCCT01 delayed flowering through suppressing the
      expression of Ehd1, Hd3a and RFT1 under both long day and short day conditions.
      Potential functions in regulating heading date of some untested CCT family genes
      were discussed. 

PMID- 25563495
TI  - Ultra-thin strut cobalt chromium bare metal stent usage in a complex real-world
      setting. (SOLSTICE registry).
AB  - AIM: To report clinical follow-up at 6 months after implantation of the ultra
      thin strut cobalt chromium SolarFlex stent in a real-world setting. METHODS AND
      RESULTS: Patients (n = 240) with single or multiple vessel coronary artery
      disease undergoing percutaneous coronary intervention (PCI) at four sites in
      Europe were enrolled in the SOLSTICE (SolarFlex Stent in Routine Clinical
      Practice) registry. Follow-up at 6 months was 100 %. Diabetes was present in 29 %
      of the patients, 30 % presented with acute myocardial infarction and 17 % had
      unstable angina. Of the patients, 27 % had previously undergone PCI or coronary
      artery bypass surgery. Lesion complexity was high (50 % B2 + C type lesions).
      Device success was achieved in 99.7 % of cases and the major adverse cardiac
      event (MACE) rate was 5.8 % at 6 months of follow-up. Target lesion
      revascularisation (TLR) was 5.0 % at 6 months. CONCLUSIONS: The SOLSTICE registry
      showed that in a complex real-world setting the SolarFlex bare metal stent, with
      ultra-thin struts and customised scaffolding, provided low clinical MACE and TLR
      rates. These results provide support for the use of the latest generation bare
      metal stent in contemporary European practice.

PMID- 25563497
TI  - Experimental tests of hypotheses for microsaccade generation.
AB  - Fixational eye movements such as microsaccades are important to prevent fading.
      These miniature eye movements are also necessary to redirect gaze to the target
      after a drift. Generation of saccades and microsaccades utilizes common neural
      substrates. We, therefore, hypothesized that physiological modulators of saccades
      should also affect microsaccades. Test of this hypothesis will also provide
      support for the models of a microsaccade generation. We performed two
      experiments. In the first experiment, complete darkness led to a decrease in the
      frequency and velocity, but increased the amplitude of microsaccades. In the
      second experiment, active eyelid closure further reduced the velocity and
      frequency of microsaccades, but increased their amplitude. Darkness reduces the
      superior colliculus activity leading to a reduction in the velocity and frequency
      of microsaccades. Eye closure might cause sustained inhibition of the omnipause
      neurons. Subsequent disinhibition of the burst neurons might cause a reduction in
      the post-inhibitory rebound firing resulting in a decreased velocity of
      microsaccades. Sustained inhibition of the omnipause neurons could also reduce
      the inhibitory drive that would otherwise abort microsaccades. Hence, by
      inhibiting the activity of omnipause neurons, the eye closure could increase the
      amplitude of microsaccades. 

PMID- 25563496
TI  - The uses and interpretations of the motor-evoked potential for understanding
      behaviour.
AB  - The motor-evoked potential (MEP) elicited in peripheral muscles by transcranial
      magnetic stimulation (TMS) over human motor cortex is one of the hallmark
      measures for non-invasive quantification of cortical and spinal excitability in
      cognitive and clinical neuroscience. In the present article, we distinguish three
      main uses for MEPs in studies of behaviour: for understanding execution and
      performance of actions, as markers of physiological change in the motor system,
      and as read-out of upstream processes influencing the motor system. Common to all
      three approaches is the assumption that different experimental manipulations act
      on the balance of excitatory and inhibitory pre-synaptic (inter)neurons at the
      stimulation site; this in turn contributes to levels of (post-synaptic)
      excitability of cortico-spinal output projections, which ultimately determines
      the size of MEPs recorded from peripheral muscles. We discuss the types of
      inference one can draw from human MEP measures given that the detailed
      physiological underpinnings of MEPs elicited by TMS are complex and remain
      incompletely understood. Awareness of the different mechanistic assumptions
      underlying different uses of MEPs can help inform both study design and
      interpretation of results obtained from human MEP studies of behaviour.

PMID- 25563498
TI  - Suppression of Toll-like receptor-mediated innate immune responses at the ocular
      surface by the membrane-associated mucins MUC1 and MUC16.
AB  - Membrane-associated mucins (MAMs) expressed on the ocular surface epithelium form
      a dense glycocalyx that is hypothesized to protect the cornea and conjunctiva
      from external insult. In this study, the hypothesis that the MAMs MUC1 and MUC16,
      expressed on the apical surface of the corneal epithelium, suppress Toll-like
      receptor (TLR)-mediated innate immune responses was tested. Using an in vitro
      model of corneal epithelial cells that are cultured to express MAMs, we show that
      reduced expression of either MUC1 or MUC16 correlates with increased message and
      secreted protein levels of the proinflammatory cytokines interleukin (IL)-6, IL
      8, and tumor necrosis factor-alpha (TNF-alpha) following exposure of cells to the
      TLR2 and TLR5 agonists, heat-killed Listeria monocytogenes and flagellin,
      respectively. As mice express Muc1 (but not Muc16) in the corneal epithelium, a
      Muc1(-/-) mouse model was used to extend in vitro findings. Indeed, IL-6 and TNF
      alpha message levels were increased in the corneal epithelium of Muc1(-/-) mice,
      in comparison with wild-type mice, following exposure of enucleated eyes to the
      TLR2 and TLR5 agonists. Our results suggest that the MAMs MUC1 and MUC16
      contribute to the maintenance of immune homeostasis at the ocular surface by
      limiting TLR-mediated innate immune responses. 

PMID- 25563499
TI  - IL-1beta in eosinophil-mediated small intestinal homeostasis and IgA production.
AB  - Eosinophils are multifunctional leukocytes that reside in the gastrointestinal
      (GI) lamina propria, where their basal function remains largely unexplored. In
      this study, by examining mice with a selective deficiency of systemic eosinophils
      (by lineage ablation) or GI eosinophils (eotaxin-1/2 double deficient or CC
      chemokine receptor 3 deficient), we show that eosinophils support immunoglobulin
      A (IgA) class switching, maintain intestinal mucus secretions, affect intestinal
      microbial composition, and promote the development of Peyer's patches. Eosinophil
      deficient mice showed reduced expression of mediators of secretory IgA
      production, including intestinal interleukin 1beta (IL-1beta), inducible nitric
      oxide synthase, lymphotoxin (LT) alpha, and LT-beta, and reduced levels of
      retinoic acid-related orphan receptor gamma t-positive (ROR-gammat(+)) innate
      lymphoid cells (ILCs), while maintaining normal levels of APRIL (a proliferation
      inducing ligand), BAFF (B cell-activating factor of the tumor necrosis factor
      family), and TGF-beta (transforming growth factor beta). GI eosinophils expressed
      a relatively high level of IL-1beta, and IL-1beta-deficient mice manifested the
      altered gene expression profiles observed in eosinophil-deficient mice and
      decreased levels of IgA(+) cells and ROR-gammat(+) ILCs. On the basis of these
      collective data, we propose that eosinophils are required for homeostatic
      intestinal immune responses including IgA production and that their affect is
      mediated via IL-1beta in the small intestine. 

PMID- 25563501
TI  - Exposure to Theory-Driven Text Messages is Associated with HIV Risk Reduction
      Among Methamphetamine-Using Men Who have Sex with Men.
AB  - Fifty-two non-treatment-seeking methamphetamine-using men who have sex with men
      were enrolled in Project Tech Support, an open-label pilot study to evaluate
      whether exposure to theory-based [social support theory (SST), social cognitive
      theory (SCT), and health belief model (HBM)] text messages could promote
      reductions in HIV sexual risk behaviors and/or methamphetamine use. Multivariable
      analyses revealed that increased relative exposure to HBM or SCT (vs. SST) text
      messages was associated with significant reductions in the number of HIV
      serodiscordant unprotected (i.e., without a condom) anal sex partners, engagement
      in sex for money and/or drugs, and frequency of recent methamphetamine use;
      additionally, increased relative exposure to HBM (vs. SCT or SST) messages was
      uniquely associated with reductions in the overall number of non-primary anal sex
      partners (all p <= 0.05, two-tailed). Pilot data demonstrated that text messages
      based on the principles of HBM and SCT reduced sentinel HIV risk and drug use
      behaviors in active methamphetamine users.

PMID- 25563500
TI  - Neutrophils negatively regulate induction of mucosal IgA responses after
      sublingual immunization.
AB  - Induction of mucosal immunoglobulin-A (IgA) capable of providing a first line of
      defense against bacterial and viral pathogens remains a major goal of needle-free
      vaccines given via mucosal routes. Innate immune cells are known to play a
      central role in induction of IgA responses by mucosal vaccines, but the relative
      contribution of myeloid cell subsets to these responses has not firmly been
      established. Using an in vivo model of sublingual vaccination with Bacillus
      anthracis edema toxin (EdTx) as adjuvant, we examined the role of myeloid cell
      subsets for mucosal secretory IgA responses. Sublingual immunization of wild-type
      mice resulted in a transient increase of neutrophils in sublingual tissues and
      cervical lymph nodes. These mice later developed Ag-specific serum IgG responses,
      but not serum or mucosal IgA. Interestingly, EdTx failed to increase neutrophils
      in sublingual tissues and cervical lymph nodes of IKKbeta(DeltaMye) mice, and
      these mice developed IgA responses. Partial depletion of neutrophils before
      immunization of wild-type mice allowed the development of both mucosal and serum
      IgA responses. Finally, co-culture of B cells with neutrophils from either wild
      type or IKKbeta(DeltaMye) mice suppressed secretion of IgA, but not IgM or IgG.
      These results identify a new role for neutrophils as negative regulators of IgA
      responses. 

PMID- 25563502
TI  - IknowUshould2: Feasibility of a Youth-Driven Social Media Campaign to Promote STI
      and HIV Testing Among Adolescents in Philadelphia.
AB  - A youth-driven, social media-based campaign aimed at improving knowledge about
      and increasing testing for sexually transmitted infections (STIs)/HIV among youth
      13-17 years old was assessed by: tracking website/social media use throughout the
      campaign; online survey of knowledge of and attitudes towards STI testing 9
      months after campaign launch; and comparing rates of STI testing at affiliated
      family planning clinics during the 1 year period immediately prior versus 1 year
      immediately after campaign launch. Over 1,500 youth were reached via social
      media. Survey results showed 46 % of youth had never been tested, but 70 %
      intended to test in the next 6 months. While the total number of GC/CT tests
      conducted and positive results were not significantly different pre- and post
      campaign, there was a large increase in the proportion of visits at which
      Syphilis (5.4 vs. 18.8 %; p < 0.01) and HIV (5.4 vs. 19.0 %; p < 0.01) testing
      was conducted post-campaign launch. Future campaigns should incorporate lessons
      learned about engaging younger adolescents, social media strategies, and specific
      barriers to testing in this age group.

PMID- 25563504
TI  - Iodine-deficiency disorders in the Aseer region, south-western Saudi Arabia: 20
      years after the national survey and universal salt iodization.
AB  - OBJECTIVE: To study (i) the current prevalence of iodine-deficiency disorders
      among schoolchildren in south-western Saudi Arabia after universal salt
      iodization and (ii) the iodine content of table salts and water. DESIGN: Cross
      sectional study on a stratified proportional allocation sample of children.
      Thyroid gland enlargement was assessed clinically and by ultrasound scanning.
      Urine, table salt and water samples were taken to measure iodine content.
      Settings The Aseer region, south-western Saudi Arabia. SUBJECTS: Schoolchildren
      aged 8-10 years. RESULTS: The study included 3046 schoolchildren. The total
      goitre rate amounted to 24.0 %. Prevalence of enlarged thyroid by ultrasound was
      22.7 %. The median urinary iodine concentration of the study sample amounted to
      17.0 ug/l. The iodine content of table salt ranged from 0 to 112 mg/kg; 22.5 % of
      the table salt samples were below the recommended iodine content (15 mg/kg) set
      by WHO. The total goitre rate increased significantly from 19.8 % among children
      using table salt with iodine content >=15 mg/kg to reach 48.5 % among children
      using table salt with 0 mg iodine/kg. Analysis of water samples taken from
      schools showed that the majority of water samples (78.8 %) had an iodine content
      of 0 ug/l. CONCLUSIONS: The study documented that 18 years after the national
      study, and after more than a decade of universal salt iodization in Saudi Arabia,
      the problem of iodine-deficiency disorders is still endemic in the Aseer region.
      Efforts should focus on fostering advocacy and communication and ensuring the
      availability of adequately iodized salt.

PMID- 25563506
TI  - Recent advances in development of imidazo[1,2-a]pyrazines: synthesis, reactivity
      and their biological applications.
AB  - Imidazo[1,2-a]pyrazine acts as a versatile scaffold in organic synthesis and drug
      development. This review article is an effort to compile the progress made in
      synthetic methods and to illustrate its reactivity and multifarious biological
      activity. This review is mainly based on the pattern and position of the
      substitution, and should help the scientific community to bring about future
      developments. 

PMID- 25563505
TI  - Constitutively active AR-V7 plays an essential role in the development and
      progression of castration-resistant prostate cancer.
AB  - This study aimed to investigate the role of AR-V7 in development of castration
      resistant prostate cancer (CRPC) and to determine whether the AR-V7 expression in
      CRPC tissues can predict cancer-specific survival. We enrolled 100 localized
      prostate cancer (PCa) (cohort 1), 104 newly diagnosed metastatic PCa (cohort 2),
      and 46 CRPC (cohort 3) patients treated at our institution. The expression of AR
      V7 in PCa was assessed by immunohistochemistry. Cox regression models were used
      to evaluate the predictive role of all covariates for the development of CRPC in
      cohort 2 and for cancer-specific survival in cohort 3. Time to CRPC and cancer
      specific survival curves were estimated using the Kaplan-Meier method. AR-V7
      expression rate in cohort 3 was significantly elevated compared with other two
      cohorts (p < 0.001). Multivariate analysis revealed that AR-V7 was an independent
      predictive factor for CRPC development (HR = 2.627, p = 0.001) and for cancer
      specific survival (HR = 2.247, p = 0.033). Furthermore, the AR-V7 expression was
      associated with shorter survival in CRPC patients. Our results demonstrated
      protein AR-V7 levels in primary tumors can be used as a predictive marker for the
      development of CRPC and as a prognostic factor in CRPC patients. Therapy
      targeting AR-V7 may help prevent PCa progression and improve the prognosis of
      CRPC patients. 

PMID- 25563503
TI  - Self-reported race/ethnicity in the age of genomic research: its potential impact
      on understanding health disparities.
AB  - This review explores the limitations of self-reported race, ethnicity, and
      genetic ancestry in biomedical research. Various terminologies are used to
      classify human differences in genomic research including race, ethnicity, and
      ancestry. Although race and ethnicity are related, race refers to a person's
      physical appearance, such as skin color and eye color. Ethnicity, on the other
      hand, refers to communality in cultural heritage, language, social practice,
      traditions, and geopolitical factors. Genetic ancestry inferred using ancestry
      informative markers (AIMs) is based on genetic/genomic data. Phenotype-based
      race/ethnicity information and data computed using AIMs often disagree. For
      example, self-reporting African Americans can have drastically different levels
      of African or European ancestry. Genetic analysis of individual ancestry shows
      that some self-identified African Americans have up to 99% of European ancestry,
      whereas some self-identified European Americans have substantial admixture from
      African ancestry. Similarly, African ancestry in the Latino population varies
      between 3% in Mexican Americans to 16% in Puerto Ricans. The implication of this
      is that, in African American or Latino populations, self-reported ancestry may
      not be as accurate as direct assessment of individual genomic information in
      predicting treatment outcomes. To better understand human genetic variation in
      the context of health disparities, we suggest using "ancestry" (or
      biogeographical ancestry) to describe actual genetic variation, "race" to
      describe health disparity in societies characterized by racial categories, and
      "ethnicity" to describe traditions, lifestyle, diet, and values. We also suggest
      using ancestry informative markers for precise characterization of individuals'
      biological ancestry. Understanding the sources of human genetic variation and the
      causes of health disparities could lead to interventions that would improve the
      health of all individuals.

PMID- 25563507
TI  - Assessing the physical environment of older people's residential care facilities:
      development of the Swedish version of the Sheffield Care Environment Assessment
      Matrix (S-SCEAM).
AB  - BACKGROUND: There is emerging evidence that the physical environment is important
      for health, quality of life and care, but there is a lack of valid instruments to
      assess health care environments. The Sheffield Care Environment Assessment Matrix
      (SCEAM), developed in the United Kingdom, provides a comprehensive assessment of
      the physical environment of residential care facilities for older people. This
      paper reports on the translation and adaptation of SCEAM for use in Swedish
      residential care facilities for older people, including information on its
      validity and reliability. METHODS: SCEAM was translated into Swedish and back
      translated into English, and assessed for its relevance by experts using content
      validity index (CVI) together with qualitative data. After modification, the
      validity assessments were repeated and followed by test-retest and inter-rater
      reliability tests in six units within a Swedish residential care facility that
      varied in terms of their environmental characteristics. RESULTS: Translation and
      back translation identified linguistic and semantic related issues. The results
      of the first content validity analysis showed that more than one third of the
      items had item-CVI (I-CVI) values less than the critical value of 0.78. After
      modifying the instrument, the second content validation analysis resulted in I
      CVI scores above 0.78, the suggested criteria for excellent content validity.
      Test-retest reliability showed high stability (96% and 95% for two independent
      raters respectively), and inter-rater reliability demonstrated high levels of
      agreement (95% and 94% on two separate rating occasions). Kappa values were very
      good for test-retest (kappa = 0.903 and 0.869) and inter-rater reliability (kappa
      = 0.851 and 0.832). CONCLUSIONS: Adapting an instrument to a domestic context is
      a complex and time-consuming process, requiring an understanding of the culture
      where the instrument was developed and where it is to be used. A team, including
      the instrument's developers, translators, and researchers is necessary to ensure
      a valid translation and adaption. This study showed preliminary validity and
      reliability evidence for the Swedish version (S-SCEAM) when used in a Swedish
      context. Further, we believe that the S-SCEAM has improved compared to the
      original instrument and suggest that it can be used as a foundation for future
      developments of the SCEAM model.

PMID- 25563508
TI  - Pyrazine-imide complexes: reversible redox and MOF building blocks.
AB  - The synthesis of the symmetric pyrazine imide ligand, N-(2-pyrazylcarbonyl)-2
      pyrazinecarboxamide, (Hdpzca) and five new first row transition metal complexes
      of it are reported: [M(II)(dpzca)(2)], M(II) = Fe, Cu, Zn;
      [Cu(II)(dpzca)(H(2)O)(2)]BF(4), [Cu(II)(dpzca)(H(2)O)(3)](2)SiF(6). The crystal
      structures of Hdpzca, [Co(II)(dpzca)(2)], [Cu(II)(dpzca)(2)],
      {[Co(III)(dpzca)(2)](BF(4))}(2).5CH(3)CN and
      [Cu(II)(dpzca)(H(2)O)(3))](2)SiF(6).2H(2)O were determined and reveal an
      orthogonal positioning of the 'spare' pyrazine nitrogen atoms and 'spare' pairs
      of imide oxygen atoms. The [M(II)(dpzca)(2)] complexes are therefore useful six
      coordinate building blocks for producing larger supramolecular assemblies. Two
      examples of secondary assembly of [M(II)(dpzca)(2)] complexes, with M = Co and
      Ni, with silver nitrate gave single crystals;
      {[Co(III)(dpzca)(2)Ag](NO(3))(2).2H(2)O}n and
      {([Ni(II)(dpzca)(2)Ag(I)(1/2)](1/2NO(3))(xH(2)O}n were structurally
      characterised. The redox processes of [M(II)(dpzca)(2)], with M(II) = Fe, Ni, Cu
      and Zn, are reported and, as seen for M(II) = Co, reversible metal- and ligand
      based redox processes are observed, with E(m)(M(II)/M(III)) values 0.15-0.24 V
      higher than for the analogous complexes of Hpypzca (non-symmetric
      pyridine/pyrazine imide ligand), and 0.35-0.36 V higher than for the complexes of
      Hbpca (symmetric pyridine imide ligand).

PMID- 25563509
TI  - beta-Cyclodextrin functionalised gold nanoclusters as luminescence probes for the
      ultrasensitive detection of dopamine.
AB  - A novel luminescence probe based on mono-6-amino-beta-cyclodextrin (NH2-beta-CD)
      functionalised gold nanoclusters (beta-CD-AuNC) was designed for dopamine (DA)
      detection. The NH2-beta-CD molecules were conjugated onto the surface of 11
      mercaptoundecanoic acid capped AuNCs (11-MUA-AuNC) via a carbodiimide coupling
      reaction. The integrity of the beta-CD cavities was preserved on the surface of
      AuNCs and they retained their capability for molecular DA host-guest recognition.
      DA could be captured by the beta-CD cavities to form an inclusion complex in
      which the oxidised DA could quench the fluorescence of the beta-CD-AuNC probe by
      electron transfer. The probe could be used to quantify DA in the range of 5-1000
      nM with a detection limit of 2 nM. This sensitivity was 1-2 orders of magnitude
      higher than that in previously reported methods. Interference by both ascorbic
      acid (AA) and uric acid (UA) was not observed. Therefore, the beta-CD-AuNC probe
      could be directly used to determine the DA content in biological samples without
      further separation. This strategy was successfully applied to a DA assay in
      spiked human serum samples and it exhibited remarkable accuracy, sensitivity and
      selectivity. 

PMID- 25563510
TI  - Preassembly-driven ratiometric sensing of H2PO4(-) anions in organic and aqueous
      environments.
AB  - Gemini surfactant-like receptor is designed and synthesized. The special
      preassembly phenomenon of in a nonpolar solvent facilitates the novel ratiometric
      fluorescence sensing of H2PO4(-)via an anion-induced reassembly process in
      organic solvents and an anion-induced disassembly process in water. 

PMID- 25563511
TI  - Recent advances bioactive 1,2,4-triazole-3-thiones.
AB  - Triazoles are heterocyclic compounds which have a five-membered ring of two
      carbon atoms and three nitrogen atoms. These structures have been interest in the
      development of novel compounds with anticonvulsant, antidepressant, antioxidant,
      anti-inflammatory, analgesic, antinociceptive, antibacterial, antimycobacterial,
      antifungal, antiviral, anticancer, anti-parasitic, anti-urease and other
      activities. Therefore, many researchers have synthesized these compounds as
      target structures and evaluated their biological activities. This review contains
      various pharmacological activities of 1,2,4-triazole-3-thiones in one place and
      it is also the milestone for the new research towards this moiety. 

PMID- 25563512
TI  - The enantioselective total synthesis of (+)-clusianone.
AB  - (+)-Clusianone, an exo-type B PPAP with reported anti-HIV and chemoprotective
      activities, was synthesized in eleven steps with 97% ee starting from
      acetylacetone. An enantioselective decarboxylative Tsuji-Trost-allylation and a
      Ru-catalyzed ring-closing metathesis-decarboxylative allylation were used to
      control both diastereo- and enantioselectivity. 

PMID- 25563513
TI  - p-Phosphonic acid calix[8]arene assisted dispersion and stabilisation of pea-pod
      C60@multi-walled carbon nanotubes in water.
AB  - A facile approach has been developed for non-covalently stabilising pristine C60
      and multi-walled carbon nanotubes (MWCNTs) in water in the presence of p
      phosphonic acid calix[8]arene, along with the formation of a 'pea-pod'
      encapsulation of the fullerene inside the MWCNTs. Aqueous dispersions of the
      different carbon nano-materials are readily decorated with palladium
      nanoparticles. 

PMID- 25563514
TI  - Dynamics of the A-band ultraviolet photodissociation of methyl iodide and ethyl
      iodide via velocity-map imaging with 'universal' detection.
AB  - We report data from a comprehensive investigation into the photodissociation
      dynamics of methyl iodide and ethyl iodide at several wavelengths in the range
      236-266 nm, within their respective A-bands. The use of non-resonant single
      photon ionization at 118.2 nm allows detection and velocity-map imaging of all
      fragments, regardless of their vibrotational or electronic state. The resulting
      photofragment kinetic energy and angular distributions and the quantum yields of
      ground-state and spin-orbit excited iodine fragments are in good agreement with
      previous studies employing state-selective detection via REMPI. The data are
      readily rationalised in terms of three competing dissociation mechanisms. The
      dominant excitation at all wavelengths studied is via a parallel transition to
      the (3)Q0 state, which either dissociates directly to give an alkyl radical
      partnered by spin-orbit excited iodine, or undergoes radiationless transfer to
      the (1)Q1 potential surface, where it dissociates to an alkyl radical partnered
      by iodine in its electronic ground state. Ground state iodine atoms can also be
      formed by direct dissociation from the (1)Q1 or (3)Q1 excited states following
      perpendicular excitation at the shorter and longer wavelength region,
      respectively, in the current range of interest. The extent of internal excitation
      of the alkyl fragment varies with dissociation mechanism, and is considerably
      higher for ethyl fragments from ethyl iodide photolysis than for methyl fragments
      from methyl iodide photolysis. We discuss the relative advantages and
      disadvantages of single-photon vacuum-ultraviolet ionization relative to the more
      widely used REMPI detection schemes, and conclude, in agreement with others, that
      single-photon ionization is a viable detection method for photofragment imaging
      studies, particularly when studying large molecules possessing multiple
      fragmentation channels. 

PMID- 25563515
TI  - Time-course human urine proteomics in space-flight simulation experiments.
AB  - BACKGROUND: Long-term space travel simulation experiments enabled to discover
      different aspects of human metabolism such as the complexity of NaCl salt
      balance. Detailed proteomics data were collected during the Mars105 isolation
      experiment enabling a deeper insight into the molecular processes involved.
      RESULTS: We studied the abundance of about two thousand proteins extracted from
      urine samples of six volunteers collected weekly during a 105-day isolation
      experiment under controlled dietary conditions including progressive reduction of
      salt consumption. Machine learning using Self Organizing maps (SOM) in
      combination with different analysis tools was applied to describe the time
      trajectories of protein abundance in urine. The method enables a personalized and
      intuitive view on the physiological state of the volunteers. The abundance of
      more than one half of the proteins measured clearly changes in the course of the
      experiment. The trajectory splits roughly into three time ranges, an early (week
      1-6), an intermediate (week 7-11) and a late one (week 12-15). Regulatory modes
      associated with distinct biological processes were identified using previous
      knowledge by applying enrichment and pathway flow analysis. Early protein
      activation modes can be related to immune response and inflammatory processes,
      activation at intermediate times to developmental and proliferative processes and
      late activations to stress and responses to chemicals. CONCLUSIONS: The protein
      abundance profiles support previous results about alternative mechanisms of salt
      storage in an osmotically inactive form. We hypothesize that reduced NaCl
      consumption of about 6 g/day presumably will reduce or even prevent the
      activation of inflammatory processes observed in the early time range of
      isolation. SOM machine learning in combination with analysis methods of class
      discovery and functional annotation enable the straightforward analysis of
      complex proteomics data sets generated by means of mass spectrometry.

PMID- 25563517
TI  - Subclinical hypothyroidism and neurocognitive functioning in bipolar disorder.
AB  - The aim of this study was to compare neurocognitive functioning between euthymic
      bipolar disorder (BD) patients with and without subclinical hypothyroidism (SCH).
      Patients with SCH had poorer performance than patients without SCH in measures of
      verbal memory, attention, language, and executive functions. These preliminary
      results suggest that SCH could have some impact on the neurocognitive performance
      of euthymic patients with BD and warrant further research in this field. 

PMID- 25563518
TI  - Pulmonary and coronary foreign particle embolism after central venous injection
      of liquid nutrition.
AB  - A man was found dead in his nursing bed. The responsible assistant nurse
      explained that she had administered liquid nutrition (Isosource Energy Fibre 500
      ml) via perfusion pump into the Hickman catheter, insisting that the Hickman
      catheter was a percutaneous endoscopic gastric tube. Autopsy findings were
      unspecific and could not reveal the cause of death. Histopathological
      examinations showed severe pulmonary foreign particle emboli, partially even
      emboli of the small coronary arteries. We present the pathological findings of
      the case in regard to the underlying pathophysiology.

PMID- 25563519
TI  - Pulsed laser deposited porous nano-carpets of indium tin oxide and their use as
      charge collectors in core-shell structures for dye sensitized solar cells.
AB  - Porous In2O3:Sn (ITO) films resembling from brush carpets to open moss-like
      discrete nanostructures were grown by pulsed laser deposition under low to high
      background gas pressures, respectively. The charge transport properties of these
      mesoporous substrates were probed by pulsed laser photo-current and -voltage
      transient measurements in N719 dye sensitized devices. Although the cyclic
      voltammetry and dye adsorption measurements suggest a lower proportion of electro
      active dye molecules for films deposited at the high-end background gas
      pressures, the transient measurements indicate similar electron transport rates
      within the films. Solar cell operation was achieved by the deposition of a
      conformal TiO2 shell layer by atomic layer deposition (ALD). Much of the device
      improvement was shown to be due to the TiO2 shell blocking the recombination of
      photoelectrons with the electrolyte as recombination lifetimes increased
      drastically from a few seconds in uncoated ITO to over 50 minutes in the ITO with
      a TiO2 shell layer. Additionally, an order of magnitude increase in the electron
      transport rate in ITO/TiO2 (core/shell) films was observed, giving the core-shell
      structure a superior ratio of recombination/transport times. 

PMID- 25563516
TI  - Effects of lithium on cortical thickness and hippocampal subfield volumes in
      psychotic bipolar disorder.
AB  - Relative to healthy controls, lithium free bipolar patients exhibit significant
      gray matter abnormalities. Lithium, the long-time reference standard medication
      treatment for bipolar disorder, has been proposed to be neuro-protective against
      these abnormalities. However, its effects on cortical thickness and hippocampal
      subfield (HSF) volumes remain unstudied and unclear, respectively, in bipolar
      disorder. This study included 342 healthy controls (HC), 51 lithium free PBD
      patients (NoLi), and 51 PBD patients taking lithium (Li). Regional gray matter
      thickness and HSF volume values were extracted from 3T MRI images. After matching
      NoLi and Li samples, regions where HC differed from either Li or NoLi were
      identified. In regions of significant or trending HC-NoLi difference, Li-NoLi
      comparisons were made. No significant HC-Li thickness or HSF volume differences
      were found. Significantly thinner occipital cortices were observed in NoLi
      compared to HC. In these regions, Li consistently exhibited non-significant
      trends for greater cortical thickness relative to NoLi. Significantly less volume
      was observed in NoLi compared to both HC and Li in right HSFs. Our results
      suggest that PBD in patients not treated with Li is associated with thinner
      occipital cortices and reduced HSF volumes compared with HC. Patients treated
      with Li exhibited significantly larger HSF volumes than NoLi, and those treated
      with Li were no different from HC in cortical thickness or hippocampal volumes.
      This evidence directly supports the hypothesis that Li may counteract the locally
      thinner and smaller gray matter structure found in PBD. 

PMID- 25563520
TI  - Breaking bad news, the diagnosis of cystic fibrosis in childhood.
AB  - BACKGROUND: The day parents are told their child has cystic fibrosis (CF) is
      imprinted in their memory. Parents often show strong emotions (e.g. shock,
      anxiety); they need to cope with bad news and restructure their lives taking into
      account CF. AIMS: The aims of this study are (1) to explore how parents recall
      circumstances of the CF diagnosis and the information they received and (2) to
      investigate their current coping styles. METHODS: Parents (n=38) of 20 children
      (diagnosed during the past 5 years) were interviewed using a semi-structured
      interview. Coping was assessed using the Utrecht Coping List. The association
      between coping and time since diagnosis/severity of illness was investigated.
      RESULTS: Fifteen parents first heard the term 'CF' from their local pediatrician
      or GP. All were informed in detail by the CF specialist. All parents recalled
      specifics about the information, the attitude of the doctor, their thoughts and
      emotions. Most parents were satisfied with the content and manner in which they
      had received information. Nineteen appreciated the doctor showing some emotions
      during the talks. One couple criticized the doctor for not showing emotions.
      Parents reported higher use (than normative scores) of the active coping style
      'social support seeking' and the accommodative coping styles 'palliative reaction
      pattern' and 'comforting cognitions'. Perception of severity of illness was
      associated with higher scores on palliative coping. CONCLUSIONS: This study shows
      the importance of physicians and CF teams to tailor the way of providing bad news
      to parents' needs and preferences. It is important to help and encourage parents
      to use active or accommodative coping strategies. The diagnosis is the starting
      point of a long-term relationship. 'Doing things well from the start' helps
      families to learn to live with CF and treatment.

PMID- 25563521
TI  - Clinical relevance of Pseudomonas aeruginosa hypermutation in cystic fibrosis
      chronic respiratory infection.

PMID- 25563523
TI  - Pain-only complaint about cochlear implant device: A five-patient pediatric
      experience.
AB  - OBJECTIVES: To present the case histories and management of five pediatric
      patients who experienced pain at the receiver-stimulator site, but no other
      indication that the device was failing. Patients were from a sole-surgeon
      pediatric practice (600 + implant surgeries before June 2013; about even
      proportions of Advanced Bionics, Cochlear Corporation, and MED-EL devices).
      METHODS: The University Institutional Review Board-approved review of sole
      surgeon pediatric case series. RESULTS: The onset of pain ranged from 2 to 16
      years post implantation. Pain, not amenable to conventional medical therapy, was
      present regardless of whether or not the external appliance was 'on', or even
      being worn on the head. Four of the five patients were bilaterally implanted, but
      pain was only at one receiver-stimulator package. Clinical management ultimately
      included revision surgery in all five cases, with immediate resolution of the
      pain in four. For those four, the replacement cochlear implant (CI) performed
      well; the other patient fears pain if her replacement device is used, but
      continues enjoying her contralateral implant. At analysis by the company, two of
      five explanted devices exhibited problems: loss of hermeticity; insulation
      failure. DISCUSSION: Though infrequently reported, pain-only complaint by a CI
      user is a challenging dilemma. CONCLUSION: Pain may be the sole clinical
      manifestation of cochlear implant device failure. We offer a flowchart for the
      care of CI patients with pain, encourage a worldwide registry of such cases, and
      offer ideas to try to understand better the problem.

PMID- 25563524
TI  - Inertial focusing of spherical particles in rectangular microchannels over a wide
      range of Reynolds numbers.
AB  - Inertial microfluidics has emerged as an important tool for manipulating
      particles and cells. For a better design of inertial microfluidic devices, we
      conduct 3D direct numerical simulations (DNS) and experiments to determine the
      complicated dependence of focusing behaviour on the particle size, channel aspect
      ratio, and channel Reynolds number. We find that the well-known focusing of the
      particles at the two centers of the long channel walls occurs at a relatively low
      Reynolds number, whereas additional stable equilibrium positions emerge close to
      the short walls with increasing Reynolds number. Based on the numerically
      calculated trajectories of particles, we propose a two-stage particle migration
      which is consistent with experimental observations. We further present a general
      criterion to secure good focusing of particles for high flow rates. This work
      thus provides physical insight into the multiplex focusing of particles in
      rectangular microchannels with different geometries and Reynolds numbers, and
      paves the way for efficiently designing inertial microfluidic devices. 

PMID- 25563522
TI  - Pseudomonas aeruginosa genotypes acquired by children with cystic fibrosis by age
      5-years.
AB  - BACKGROUND: We describe Pseudomonas aeruginosa acquisitions in children with
      cystic fibrosis (CF) aged <=5-years, eradication treatment efficacy, and
      genotypic relationships between upper and lower airway isolates and strains from
      non-CF sources. METHODS: Of 168 CF children aged <=5-years in a bronchoalveolar
      lavage (BAL)-directed therapy trial, 155 had detailed microbiological results.
      Overall, 201/271 (74%) P. aeruginosa isolates from BAL and oropharyngeal cultures
      were available for genotyping, including those collected before and after
      eradication therapy. RESULTS: Eighty-two (53%) subjects acquired P. aeruginosa,
      of which most were unique strains. Initial eradication success rate was 90%, but
      36 (44%) reacquired P. aeruginosa, with genotypic substitutions more common in
      BAL (12/14) than oropharyngeal (3/11) cultures. Moreover, oropharyngeal cultures
      did not predict BAL genotypes reliably. CONCLUSIONS: CF children acquire
      environmental P. aeruginosa strains frequently. However, discordance between BAL
      and oropharyngeal strains raises questions over upper airway reservoirs and how
      to best determine eradication in non-expectorating children.

PMID- 25563525
TI  - Effect of osteogenic periosteal distraction by a modified Hyrax device with and
      without platelet-rich fibrin on bone formation in a rabbit model: a pilot study.
AB  - This study evaluated the effect of a modified Hyrax device and platelet-rich
      fibrin (PRF) on osteogenic periosteal distraction (OPD). Twelve adult male New
      Zealand white rabbits were separated into two main groups (six in each) according
      to the duration of the consolidation period (4 or 8 weeks). In each main group,
      the animals underwent OPD of the left and right sides of the mandible and were
      divided into four subgroups (three animals per group): device vs. device+PRF, and
      PRF vs. sham. Radiographic, histological, histomorphometric, and micro-computed
      tomography (micro-CT) analyses were performed. New bone formation was observed on
      the lateral and vertical sides of the mandible of all groups. Micro-CT and
      histomorphometry showed that the device+PRF group presented the highest
      percentages of bone volume and bone area at 4 weeks (56.67 +/- 12.67%, 41.37 +/-
      7.57%) and at 8 weeks (49.67 +/- 8.33%, 55.46 +/- 10.67%; significantly higher
      than the other groups, P<0.001), followed by the device group at 4 weeks (33.00
      +/- 1.73%, 33.21 +/- 11.00%) and at 8 weeks (30.00 +/- 3.00%, 23.25 +/- 5.46%).
      In conclusion, the modified Hyrax device was used successfully for OPD in a
      rabbit model to gain vertical ridge augmentation, and greater bone maturation was
      achieved with the addition of PRF.

PMID- 25563526
TI  - A new technique for the surgical repair of double cleft earlobe: modified
      Millard's rotation-advancement flap.
AB  - The double cleft earlobe is a rare earlobe deformation. The most common causes of
      cleft earlobe are earring or piercing tear injuries and trauma. In this study,
      the cases of five patients (all women) attending the clinic between 2010 and 2013
      suffering from a unilateral traumatic complete double earlobe cleft as a result
      of an earring injury were evaluated. The principles of Millard's cleft lip repair
      were applied during the repair of these double cleft earlobe deformities. This
      adaptation of Millard's technique to repair double earlobe clefts with a non
      straight closure appears to give satisfactory results. 

PMID- 25563527
TI  - [Screening with angiographic images prior to (99m)Tc-HMPAO labelled leukocyte
      scintigraphy in the diagnosis of periprosthetic infection].
AB  - AIM: To evaluate the impact of the angioscintigrapy of the three phase bone scan
      as screening method to rule out infection of the hip and knee prosthesis prior to
      performing the (99m)Tc-HMPAO leukocyte scintigraphy. MATERIAL AND METHODS: A
      total of 120 (70 women, 50 men; mean age 71+/-11years) with clinical suspicion of
      hip (n=63) or knee (n=57) infection of the prosthesis and clinical suspicion of
      infection were evaluated prospectively. All patients underwent three-phase bone
      scan (angioscintigraphy, vascular and bone phase) and (99m)Tc-HMPAO-labelled
      white blood cell scintigraphy. Final diagnosis of infection was made by
      microbiological documentation or clinical follow-up for at least 12months.
      RESULTS: Eighteen out of 120 patients were diagnosed of infection of hip
      prosthesis (n=10) or knee prosthesis (n=8). The angioscintigraphy was positive in
      15/18 infected cases and in 21/102 of the non-infected cases with a sensitivity
      of 83%, specificity of 79% and negative predictive value of 97%. Sensitivity and
      specificity of (99m)Tc-HMPAO leukocyte scintigraphy were 72% and 95%,
      respectively. If the leukocyte labeled scintigraphies had been used exclusively
      for patients with positive angioscintigraphy, this would have saved up to 70% of
      the (99m)Tc-HMPAO leukocyte scintigraphies performed. There were no cases of
      infection with positive labeled leukocyte scintigraphy and negative
      angioscintigraphy. CONCLUSION: Angioscintigraphy (blood flow phase of bone scan)
      is a useful technique for screening for hip and knee joint prosthesis infection,
      significantly reducing the need for (99m)Tc-HMPAO leukocyte scintigraphy without
      affecting the sensitivity of the technique.

PMID- 25563530
TI  - Drop-out from the Swedish addiction compulsory care system.
AB  - Drop-out of addiction treatment is common, however, little is known about drop
      out of compulsory care in Sweden. Data from two national register databases were
      merged to create a database of 4515 individuals sentenced to compulsory care 2001
      2009. The study examined (1) characteristics associated with having dropped out
      from a first compulsory care episode, (2) the relationship between drop-out and
      returning to compulsory care through a new court sentence, and (3) the
      relationship between drop-out and mortality. METHODS: Multivariable logistic
      regression analysis was used to address Aim 1 and Cox proportional hazards
      regression modeling was applied to respond to Aims 2 and 3. FINDINGS: Age and
      previous history of crime were significant predictors for drop-out. Clients who
      dropped out were 1.67 times more likely to return to compulsory care and the
      hazard of dying was 16% higher than for those who dropped-out. CONCLUSION: This
      study finds that 59% of clients assigned to compulsory care drop-out. Younger
      individuals are significantly more likely to drop-out. Those who drop out are
      significantly more likely to experience negative outcomes (additional sentence to
      compulsory care and higher risk of mortality). Interventions need to be
      implemented that increase motivation of youth to remain in compulsory care.

PMID- 25563531
TI  - Antimalarial compounds in Phase II clinical development.
AB  - INTRODUCTION: Malaria is a major health problem in endemic countries and
      chemotherapy remains the most important tool in combating it. Treatment options
      are limited and essentially rely on a single drug class - the artemisinins.
      Efforts are ongoing to restrict the evolving threat of artemisinin resistance but
      declining sensitivity has been reported. Fueled by the ambitious aim of malaria
      eradication, novel antimalarial compounds, with improved properties, are now in
      the progressive phase of drug development. AREAS COVERED: Herein, the authors
      describe antimalarial compounds currently in Phase II clinical development and
      present the results of these investigations. EXPERT OPINION: Thanks to recent
      efforts, a number of promising antimalarial compounds are now in the pipeline.
      First safety data have been generated for all of these candidates, although their
      efficacy as antimalarials is still unclear for most of them. Of particular note
      are KAE609, KAF156 and DSM265, which are of chemical scaffolds new to malaria
      chemotherapy and would truly diversify antimalarial options. Apart from SAR97276,
      which also has a novel chemical scaffold that has had its development stopped,
      all other compounds in the pipeline belong to already known substance classes,
      which have been chemically modified. At this moment in time, there is not one
      standout compound that will revolutionize malaria treatment but several compounds
      that will add to its control in the future.

PMID- 25563532
TI  - Predicting the probability of slip in gait: methodology and distribution study.
AB  - The likelihood of a slip is related to the available and required friction for a
      certain activity, here gait. Classical slip and fall analysis presumed that a
      walking surface was safe if the difference between the mean available and
      required friction coefficients exceeded a certain threshold. Previous research
      was dedicated to reformulating the classical slip and fall theory to include the
      stochastic variation of the available and required friction when predicting the
      probability of slip in gait. However, when predicting the probability of a slip,
      previous researchers have either ignored the variation in the required friction
      or assumed the available and required friction to be normally distributed. Also,
      there are no published results that actually give the probability of slip for
      various combinations of required and available frictions. This study proposes a
      modification to the equation for predicting the probability of slip, reducing the
      previous equation from a double-integral to a more convenient single-integral
      form. Also, a simple numerical integration technique is provided to predict the
      probability of slip in gait: the trapezoidal method. The effect of the random
      variable distributions on the probability of slip is also studied. It is shown
      that both the required and available friction distributions cannot automatically
      be assumed as being normally distributed. The proposed methods allow for any
      combination of distributions for the available and required friction, and
      numerical results are compared to analytical solutions for an error analysis. The
      trapezoidal method is shown to be highly accurate and efficient. The probability
      of slip is also shown to be sensitive to the input distributions of the required
      and available friction. Lastly, a critical value for the probability of slip is
      proposed based on the number of steps taken by an average person in a single day.

PMID- 25563529
TI  - Variability in the prescription of non-biologic disease-modifying antirheumatic
      drugs for the treatment of spondyloarthritis in Spain.
AB  - OBJECTIVE: To describe the variability in the prescription of non-biologic
      disease-modifying antirheumatic drugs (nbDMARDs) for the treatment of
      spondyloarthritis (SpA) in Spain and to explore which factors relating to the
      disease, patient, physician, and/or center contribute to these variations.
      METHODS: A retrospective medical record review was performed using a
      probabilistic sample of 1168 patients with SpA from 45 centers distributed in
      15/19 regions in Spain. The sociodemographic and clinical features and the use of
      drugs were recorded following a standardized protocol. Logistic regression, with
      nbDMARDs prescriptions as the dependent variable, was used for bivariable
      analysis. A multilevel logistic regression model was used to study variability.
      RESULTS: The probability of receiving an nbDMARD was higher in female patients
      [OR = 1.548; 95% confidence interval (CI): 1.208-1.984], in those with elevated C
      reactive protein (OR = 1.039; 95% CI: 1.012-1.066) and erythrocyte sedimentation
      rate (OR = 1.012; 95% CI: 1.003-1.021), in those with a higher number of affected
      peripheral joints (OR = 12.921; 95% CI: 2.911-57.347), and in patients with extra
      articular manifestations like dactylitis (OR = 2.997; 95% CI: 1.868-4.809),
      psoriasis (OR = 2.601; 95% CI: 1.870-3.617), and enthesitis (OR = 1.717; 95% CI:
      1.224-2.410). There was a marked variability in the prescription of nbDMARDs for
      SpA patients, depending on the center (14.3%; variance 0.549; standard error
      0.161; median odds ratio 2.366; p < 0.001). After adjusting for patient and
      center variables, this variability fell to 3.8%. CONCLUSION: A number of factors
      affecting variability in clinical practice, and which are independent of disease
      characteristics, are associated with the probability of SpA patients receiving
      nbDMARDs in Spain.

PMID- 25563533
TI  - Circulating levels of TNF-like cytokine 1A correlate with reflected waves and
      atherosclerosis extent and may predict cardiac death in patients with stable
      coronary artery disease.
AB  - BACKGROUND: TNF-like cytokine 1A (TL1A)-mediated interactions are involved in
      atheromatic plaque formation. In stable coronary artery disease (CAD) we examined
      whether circulating TL1A levels correlate with coronary and/or peripheral
      atherosclerosis extent and predict future cardiovascular events. METHODS: In this
      cross-sectional study, peripheral vascular studies and TL1A serum measurements
      were performed in 122 consecutive patients with angiographically confirmed CAD
      who were followed for a median of 41.9 months. TL1A levels were compared against
      controls (n = 63) and 20 patients with acute coronary syndrome (ACS). RESULTS:
      TL1A was higher in ACS than the 2 other groups (p < 0.001). In stable CAD, after
      adjustment for traditional risk factors independent positive correlations between
      TL1A serum levels and reflected waves (p = 0.049), and carotid atheromatic plaque
      score (p = 0.049) were evident. In stable patients with a history of ACS, TL1A
      levels correlated with worse endothelial function (p = 0.006), extent of CAD
      assessed by Gensini score (p = 0.042), and cardiac mortality (p = 0.051).
      CONCLUSIONS: This pilot study suggests that serum TL1A measurements are of
      clinical value in CAD. Studies on the pathogenetic role of TL1A in
      atherosclerosis and its sequelae are warranted.

PMID- 25563534
TI  - Improving sleep: outcomes from a worksite healthy sleep program.
AB  - OBJECTIVE: Unhealthy and inadequate sleep is a common and significant problem
      impacting absenteeism, presenteeism, health, and productivity. This study aimed
      at analyzing the effect of a worksite-based healthy sleep program. METHODS:
      Retrospective analysis of 53 adult members of a worksite wellness center who
      participated in an 8-week healthy sleep program and completed pre- and
      postintervention health behavior questionnaires. RESULTS: Following the
      intervention participants felt significantly more rested, more confident in their
      ability to deal with sleep problems, and more knowledgeable about sleep. In
      addition, they reported a reduction in their stress level, improved quality of
      life, and increase energy level. CONCLUSIONS: These results support the
      effectiveness of worksite programs designed to promote healthy sleep. Future
      randomized studies are needed to further investigate the effectiveness and
      optimal delivery of healthy sleep promotion.

PMID- 25563535
TI  - HRCT/CT and associated spirometric effects of low Libby amphibole asbestos
      exposure.
AB  - OBJECTIVE: Evaluate the relationship between cumulative fiber exposure and high
      resolution or conventional chest computed tomography (HRCT/CT) changes and
      spirometry of workers with Libby amphibole asbestos exposure. METHODS: Of the
      original 1980 cohort (n = 513), 431 were living and asked to participate. Images
      were evaluated for localized pleural thickening (LPT), diffuse pleural thickening
      (DPT), and parenchymal changes. RESULTS: A total of 306 participants provided
      either HRCT/CT scans (n = 191) or chest radiographs (n = 115). Of the 191 with
      HRCT/CT, 52.9% had pleural changes and 13.1% had parenchymal changes. Those with
      LPT only, LPT and/or DPT, or DPT and/or parenchymal changes had mean 6.1, 8.0,
      and 18.0 loss in percent predicted forced vital capacity, respectively.
      CONCLUSIONS: Exposure to vermiculite containing amphibole fibers is associated
      with pleural and parenchymal HRCT/CT changes at low cumulative fiber exposure;
      these changes are associated with spirometric decrements.

PMID- 25563536
TI  - Implementation of a worksite wellness program targeting small businesses: the
      Pinnacol Assurance health risk management study.
AB  - OBJECTIVE: To assess small business adoption and need for a worksite wellness
      program in a longitudinal study of health risks, productivity, workers'
      compensation rates, and claims costs. METHODS: Health risk assessment data from
      6507 employees in 260 companies were examined. Employer and employee data are
      reported as frequencies, with means and standard deviations reported when
      applicable. RESULTS: Of the 260 companies enrolled in the health risk management
      program, 71% continued more than 1 year, with 97% reporting that worker wellness
      improves worker safety. Of 6507 participating employees, 34.3% were overweight
      and 25.6% obese. Approximately one in five participants reported depression.
      Potentially modifiable conditions affecting 15% or more of enrollees include
      chronic fatigue, sleeping problems, headaches, arthritis, hypercholesterolemia,
      and hypertension. CONCLUSIONS: Small businesses are a suitable target for the
      introduction of health promotion programs.

PMID- 25563537
TI  - The health care and productivity costs of back and neck pain in a multi-employer
      sample of utility industry employees.
AB  - OBJECTIVE: To determine the cost of back and/or neck (B/N) pain among
      predominantly rural employees insured through an employee benefits trust.
      METHODS: Eligible employees had 1 year or more of medical coverage and completed
      a survey subsequently linked to their claims data. B/N pain costs consisted of
      medical and pharmacy claims, over-the-counter expenses, and presenteeism and
      absenteeism costs valued according to median occupational earnings. RESULTS: Of
      1342 eligible employees, 52.7% currently had B/N pain of which 87.9% was chronic.
      The average annualized cost of B/N pain per employee was $1727; 56.1% was due to
      lost productivity. Covered medical care was utilized by 35.6% of employees, 55.7%
      used pharmacy care, and 71.6% purchased uncovered over-the-counter pain
      medication. CONCLUSIONS: Many covered employees did not use formal care. The
      effect of care choices on productivity costs requires closer scrutiny.

PMID- 25563539
TI  - Overweight and distress have a joint association with long-term sickness absence
      among Dutch employees.
AB  - OBJECTIVES: To examine separate and joint associations of overweight and distress
      with long-term sickness absence (LTSA). METHODS: We included a total of 2724
      Dutch employees participating in occupational health checks between 2008 and
      2012. Overweight was defined as a body mass index of 25 kg/m2 or more; distress
      concerned a score of 10 or more on the Four-Dimensional Symptom Questionnaire.
      Long-term sickness absence was defined as sickness absence lasting more than 2
      consecutive weeks. Synergy was estimated from logistic regression models using
      the synergy index. RESULTS: The joint association of overweight and distress with
      LTSA was significant in women (odds ratio, 2.35; 95% confidence interval, 1.31 to
      4.24), but not in men (odds ratio, 1.58; 95%confidence interval, 0.74 to 3.37).
      In women, we found a synergy index of 1.04 (95%confidence interval, 0.34 to
      3.15). CONCLUSIONS: The joint association of overweight and distress with LTSA
      was not synergistic. Addressing comorbid overweight and distress may help reduce
      the burden of LTSA in women.

PMID- 25563538
TI  - Isocyanates and human health: multistakeholder information needs and research
      priorities.
AB  - OBJECTIVES: To outline the knowledge gaps and research priorities identified by a
      broad base of stakeholders involved in the planning and participation of an
      international conference and research agenda workshop on isocyanates and human
      health held in Potomac, Maryland, in April 2013. METHODS: A multimodal iterative
      approach was used for data collection including preconference surveys, review of
      a 2001 consensus conference on isocyanates, oral and poster presentations,
      focused break-out sessions, panel discussions, and postconference research agenda
      workshop. RESULTS: Participants included representatives of consumer and worker
      health, health professionals, regulatory agencies, academic and industry
      scientists, labor, and trade associations. CONCLUSIONS: Recommendations were
      summarized regarding knowledge gaps and research priorities in the following
      areas: worker and consumer exposures; toxicology, animal models, and biomarkers;
      human cancer risk; environmental exposure and monitoring; and respiratory
      epidemiology and disease, and occupational health surveillance.

PMID- 25563540
TI  - Effectiveness and acceptance of a health care-based mandatory vaccination
      program.
AB  - OBJECTIVE: To decrease the risk of transmission of hospital-associated
      transmission of influenza and pertussis through mandatory vaccination of staff.
      METHODS: A mandatory influenza and toxoid-diphtheria toxoid-acellular pertussis
      program was implemented systemwide. A structured vaccine exemption program was
      implemented for those requesting a medical and/or religious/moral/ethical
      exemption. RESULTS: Systemwide influenza vaccination rates increased from 67%
      historically, 76.2% in the 2012 to 2013 influenza season, to 94.7% in 2013 to
      2014 with an overall compliance rate of 97.8%. Toxoid-diphtheria toxoid-acellular
      pertussis vaccination rates systemwide reached 94.9%, with an overall compliance
      rate of 98%. Higher rates were experienced at individual hospital facilities
      compared with the corporate location. CONCLUSIONS: Successful vaccination
      campaign outcomes can be achieved through diligent enforcement of mandatory
      vaccination, masking, and other infection prevention procedures.

PMID- 25563541
TI  - Debilitating lung disease among surface coal miners with no underground mining
      tenure.
AB  - OBJECTIVE: To characterize exposure histories and respiratory disease among
      surface coal miners identified with progressive massive fibrosis from a 2010 to
      2011 pneumoconiosis survey. METHODS: Job history, tenure, and radiograph
      interpretations were verified. Previous radiographs were reviewed when available.
      Telephone follow-up sought additional work and medical history information.
      RESULTS: Among eight miners who worked as drill operators or blasters for most of
      their tenure (median, 35.5 years), two reported poor dust control practices,
      working in visible dust clouds as recently as 2012. Chest radiographs progressed
      to progressive massive fibrosis in as few as 11 years. One miner's lung biopsy
      demonstrated fibrosis and interstitial accumulation of macrophages containing
      abundant silica, aluminum silicate, and titanium dust particles. CONCLUSIONS:
      Overexposure to respirable silica resulted in progressive massive fibrosis among
      current surface coal miners with no underground mining tenure. Inadequate dust
      control during drilling/blasting is likely an important etiologic factor.

PMID- 25563542
TI  - Kidney cancer risk in oil refining in Finland: a nested case-referent study.
AB  - OBJECTIVE: The purpose of this study was to assess whether occupational exposure
      to hydrocarbons in the oil-refining activity increases the risk of kidney cancer.
      METHODS: This case-referent study was nested within the cohort of employees in
      the oil refinery industry in Finland in 1967 to 1982 (n = 9454). The final data
      included 30 cases of kidney cancer and 81 age- and sex-matched referents.
      RESULTS: There was a threefold increase in the kidney cancer risk for exposure to
      hydrocarbons in crude oil (odds ratio, 3.1; confidence interval, 1.1 to 8.9; 11
      exposed cases). The risk was associated with the highest cumulative exposure
      category to hydrocarbons in crude oil. CONCLUSIONS: Occupational exposure in oil
      refining, particularly to crude oil, may increase kidney cancer risk. The study
      assessed historical exposures; further information needs to be collected for
      evaluating current exposures.

PMID- 25563544
TI  - Particulate matter, endotoxin, and worker respiratory health on large Californian
      dairies.
AB  - OBJECTIVE: To assess respiratory exposures and lung function in a cross-sectional
      study of California dairy workers. METHODS: Exposure of 205 dairy and 45 control
      (vegetable processing) workers to particulate matter and endotoxin was monitored.
      Pre- and postshift spirometry and interviews were conducted. RESULTS: Geometric
      mean inhalable and PM2.5 concentrations were 812 and 35.3 MUg/m3 versus 481.9 and
      19.6 MUg/m3, respectively, for dairy and control workers. Endotoxin
      concentrations were 329 EU/m3 or 1122 pmol/m3 and 13.5 EU/m3 or 110 pmol/m3,
      respectively, for dairy and control workers. In a mixed-effects model, forced
      vital capacity decreased across a work shift by 24.5 mL (95% confidence interval,
      -44.7 to -4.3; P = 0.018) with log10 (total endotoxin) and by 22.0 mL (95%
      confidence interval, -43.2 to -0.08; P = 0.042) per hour worked. CONCLUSIONS:
      Modern California dairy endotoxin exposures and shift length were associated with
      a mild acute decrease in forced vital capacity.

PMID- 25563543
TI  - Physical activity levels at work and outside of work among commercial
      construction workers.
AB  - OBJECTIVE: Characterize the number of minutes of moderate and vigorous physical
      activities at work and outside of work during seven consecutive days, in a sample
      of 55 commercial construction workers. METHODS: Workers wore accelerometers
      during work and outside-of-work hours for seven consecutive days and completed
      brief survey at the seventh day of data collection. RESULTS: From the directly
      measured physical activity, the average number per participant of moderate
      minutes of occupational physical activity and physical activity outside of work
      obtained in short bouts were 243 minutes (65%) and 130 minutes (35%),
      respectively. Directly measured minutes of vigorous occupational physical
      activity were significant and positively correlated with self-reported fatigue.
      CONCLUSIONS: Among commercial construction workers, physical activity from work
      contributes significantly, approximately two thirds, toward a worker's total
      amount of weekly minutes of moderate physical activity.

PMID- 25563545
TI  - Biomonitoring in California firefighters: metals and perfluorinated chemicals.
AB  - OBJECTIVE: To assess California firefighters' blood concentrations of selected
      chemicals and compare with a representative US population. METHODS: We report
      laboratory methods and analytic results for cadmium, lead, mercury, and manganese
      in whole blood and 12 serum perfluorinated chemicals in a sample of 101 Southern
      California firefighters. RESULTS: Firefighters' blood metal concentrations were
      all similar to or lower than the National Health and Nutrition Examination Survey
      (NHANES) values, except for six participants whose mercury concentrations (range:
      9.79 to 13.42 MUg/L) were close to or higher than the NHANES reporting threshold
      of 10 MUg/L. Perfluorodecanoic acid concentrations were elevated compared with
      NHANES and other firefighter studies. CONCLUSIONS: Perfluorodecanoic acid
      concentrations were three times higher in this firefighter group than in NHANES
      adult males. Firefighters may have unidentified sources of occupational exposure
      to perfluorinated chemicals.

PMID- 25563547
TI  - Work productivity loss with depression, diagnosed and undiagnosed, among workers
      in an Internet-based survey conducted in Japan.
AB  - OBJECTIVE: The aim of this study was to investigate whether depression severity
      was associated with work impairments, regardless of the diagnosis. METHODS: We
      conducted a cross-sectional study among 17,820 Japanese workers using an Internet
      based survey. Work impairments were assessed using the Work Productivity and
      Activity Impairment questionnaire. Participants were grouped according to whether
      they had a past-year diagnosis of depression by physicians and current depression
      severity assessed with the Patient Health Questionnaire-9. RESULTS: Among the
      undiagnosed, high severity respondents had greater overall work impairment than
      low severity respondents (33.3% vs 14.8%). Significant interactions between
      diagnosis and severity indicated greater impairments among undiagnosed than among
      diagnosed respondents (except on absenteeism). CONCLUSIONS: Depression severity
      was associated with work productivity loss, even among the undiagnosed,
      suggesting a need for early detection, referral, and treatment of depression in
      the workplace.

PMID- 25563546
TI  - Personal and workplace factors and median nerve function in a pooled study of
      2396 US workers.
AB  - OBJECTIVE: Evaluate associations between personal and workplace factors and
      median nerve conduction latency at the wrist. METHODS: Baseline data on workplace
      psychosocial and physical exposures were pooled from four prospective studies of
      production and service workers (N = 2396). During the follow-up period,
      electrophysiologic measures of median nerve function were collected at regular
      intervals. RESULTS: Significant adjusted associations were observed between age,
      body mass index, sex, peak hand force, duration of forceful hand exertions,
      Threshold Limit Value for Hand Activity Limit, forceful repetition rate, wrist
      extension, and decision latitude on median nerve latencies. CONCLUSIONS:
      Occupational and nonoccupational factors have adverse effects on median nerve
      function. Measuring median nerve function eliminates possible reporting bias that
      may affect symptom-based carpal tunnel syndrome case definitions. These results
      suggest that previously observed associations between carpal tunnel syndrome and
      occupational factors are not the result of such reporting bias.

PMID- 25563551
TI  - Comment on "Do workplace health promotion (wellness) programs work?" (September
      2014, Volume 56, Issue 9).

PMID- 25563548
TI  - Prostate-specific antigen and perfluoroalkyl acids in the C8 health study
      population.
AB  - PURPOSE: To inform questions raised by inconsistent findings regarding an
      association between perfluoroalkyl acids (PFAAs) and prostate cancer by assessing
      the relationship of PFAAs in human serum to prostate-specific antigen (PSA).
      MATERIALS AND METHODS: Using 2005 to 2006 survey data from a large survey
      population, we compared serum PFAA concentrations in adult males with PSA
      concentrations adjusted for risk factors including age, body mass index, smoking
      status, and socioeconomic status. RESULTS: Perfluoroalkyl acids are not
      consistently associated with PSA concentration in general, or with PSA more than
      4.0. DISCUSSION: These findings do not provide evidence that PFAA exposure is
      associated with PSA.

PMID- 25563552
TI  - Success overlooked--Navistar, 1999 to 2009: the huge impact an employer's
      approach to wellness can have on health care costs and sustained value.

PMID- 25563553
TI  - Response to Harris Allen, PhD.

PMID- 25563554
TI  - Comment on "Do workplace health promotion (wellness) programs work?".

PMID- 25563555
TI  - Constructing quaternary stereogenic centers using tertiary organocuprates and
      tertiary radicals. Total synthesis of trans-clerodane natural products.
AB  - A new concise construction of trans-clerodane diterpenoids is reported in which
      oxacyclic and trans-hydronaphthalene fragments are coupled, and the critical C9
      quaternary carbon stereocenter formed stereoselectively, by 1,6-addition of a
      tertiary cuprate or a tertiary carbon radical to beta-vinylbutenolide. This
      strategy is specifically illustrated by total syntheses of (-)-solidagolactone
      (4), (-)-16-hydroxycleroda-3,13-dien-15,16-olide (5, PL3), and (-)-annonene (6). 

PMID- 25563556
TI  - Real-life comparison of severe vascular events and other non-hematological
      complications in patients with chronic myeloid leukemia undergoing second-line
      nilotinib or dasatinib treatment.
AB  - We retrospectively analyzed the rates of significant non-hematological adverse
      events (AEs) in 105 patients with chronic myeloid leukemia (CML) treated with
      second-generation tyrosine kinase inhibitor (TKIs) dasatinib or nilotinib used as
      second-line therapy in Polish tertiary care centers. Our analysis revealed that
      in a "real life setting," nearly half of patients with CML on second-generation
      TKIs suffer from therapy complications. Grade 2-5 non-hematological AEs were
      observed in 40% of patients treated with nilotinib and in 42% treated with
      dasatinib (p=0.83). Severe vascular events including peripheral artery occlusive
      disease (PAOD) occurred in 11% of patients on nilotinib and 4% on dasatinib
      (p=0.16). Pleural effusion occurred more often in the dasatinib group (26%) than
      in the nilotinib group (2%) (p=0.003). Importantly, most AEs occurred late, after
      more than 1 year of treatment. Since AEs are most often the reason for poor
      therapy compliance, careful monitoring of tolerability is crucial for an optimal
      treatment response in CML.

PMID- 25563557
TI  - Rituximab-induced early and late signaling have opposite effects on dexamethasone
      induced apoptosis in human follicular lymphoma cells.
AB  - The addition of rituximab (RTX) to standard chemotherapy has improved the
      treatment of B-cell malignancies. We show here that RTX and dexamethasone (Dex)
      induced synergistic apoptosis in follicular lymphoma cell lines. However,
      apoptosis was delayed by RTX-induced early protective signaling. RTX-induced
      early signaling also decreased Dex-induced apoptosis and led to phosphorylation
      of ERK1/2, Bcl-2 (at serine 70) and phosphorylation/degradation of BimL/EL. All
      these events were prevented by the MEK inhibitor, UO126. Therefore, we suggest
      that RTX-induced ERK-mediated signaling events lead to protection from apoptosis
      during early signaling and that blocking of Bim and Bcl-2 phosphorylation might
      be used as a novel strategy for lymphoma treatment. 

PMID- 25563558
TI  - A pilot study of the safety and efficacy of dexamethasone, ifosfamide,
      methotrexate and gemcitabine chemotherapy for natural killer/T-cell lymphoma.

PMID- 25563559
TI  - Ultra-high level of serum soluble interleukin-2 receptor at diagnosis predicts
      poor outcome for angioimmunoblastic T-cell lymphoma.
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of non-Hodgkin
      lymphoma and displays an aggressive clinical course with poor outcome. To
      identify prognostic factors for AITL, we retrospectively analyzed 36 patients
      with AITL. The median age was 74 years with 83% of the patients having advanced
      stage. Eighty-three percent received CHOP (cyclophosphamide, doxorubicin,
      vincristine, prednisolone)-like chemotherapies, resulting in an overall response
      rate of 63%. With a median follow-up of 9 years, the estimated overall survival
      at 5 years was 33.3%. Median serum level of soluble interleukin-2 receptor (sIL
      2R) was 5615 U/mL at diagnosis, and over 10 000 U/mL of sIL-2R was identified as
      a significant poor prognostic factor, independent of the International Prognostic
      Index, Prognostic Index for peripheral T-cell lymphoma and Prognostic index for
      AITL (hazard ratio [HR], 4.42; 95% confidence interval [CI], 1.49-13.11; log
      rank, p < 0.01). Our study shows that an ultra-high level of serum sIL-2R at
      diagnosis is a significant poor prognostic biomarker for AITL. 

PMID- 25563560
TI  - Circulating tumor necrosis factor-alpha and YKL-40 level is associated with
      remission status following salvage therapy in relapsed non-Hodgkin lymphoma.

PMID- 25563561
TI  - The new year.

PMID- 25563562
TI  - pH-controllable on-demand oil/water separation on the switchable
      superhydrophobic/superhydrophilic and underwater low-adhesive superoleophobic
      copper mesh film.
AB  - Recently, materials with controlled oil/water separation ability became a new
      research focus. Herein, we report a novel copper mesh film, which is
      superhydrophobic and superhydrophilic for nonalkaline water and alkaline water,
      respectively. Meanwhile, the film shows superoleophobicity in alkaline water.
      Using the film as a separating membrane, the oil/water separating process can be
      triggered on-demand by changing the water pH, which shows a good controllability.
      Moreover, it is found that the nanostructure and the appropriate pore size of the
      substrate are important for realization of a good separation effect. This paper
      offers a new insight into the application of surfaces with switchable
      wettability, and the film reported here has such a special ability that allows it
      to be used in other applications, such as sewage purification, filtration, and
      microfluidic device. 

PMID- 25563563
TI  - Understanding the dynamics of rings in the melt in terms of the annealed tree
      model.
AB  - The dynamical properties of a long polymer ring in a melt of unknotted and
      unconcatenated rings are calculated. We re-examine and generalize the well known
      model of a ring confined to a lattice of topological obstacles in light of the
      recently developed Flory theory of untangled rings which maps every ring on an
      annealed branched polymer and establishes that the backbone associated with each
      ring follows self-avoiding rather than Gaussian random walk statistics. We find
      the scaling of the ring relaxation time and diffusion coefficient with ring
      length, as well as the time dependence of stress relaxation modulus, zero shear
      viscosity and the mean square averaged displacements of both individual monomers
      and the ring's mass centre. Our results agree within error bars with all
      available experimental and simulation data of the ring melt, although the quality
      of the data so far is insufficient to make a definitive judgement for or against
      the annealed tree theory. At the end we review briefly the relation between our
      findings and experimental data on chromatin dynamics. 

PMID- 25563564
TI  - The unbearable lightness of bone marrow homeostasis.
AB  - The anatomical and functional dimensions of bone marrow topography have been at
      the forefront of modern bone and immunological research for many years and remain
      a source of complexity and perplexity due to the multitude of microhabitats
      within this microenvironment. In fact, research has uncovered fascinating
      functional aspects of bone marrow residents, and the bone marrow niche has been
      identified as the foremost reservoir of a variety of cells including
      hematopoietic, skeletal and endothelial stem/progenitor cells. The physical
      interactions of the marrow residents, combined with the release of cytokines and
      growth factors, organize well-defined operative compartments, which preserve bone
      and immune cell homeostasis. In a simplistic view, both the hematopoietic and
      bone marrow stromal (mesenchymal) stem/progenitor cell populations dwell at the
      interface between the endosteum and the bone marrow area (endosteal niche) and in
      the perivascular space (vascular niche). Indeed, the tantalizing hypothesis of
      bone marrow regulatory dependency on these niches is supported by current
      research insofar as the increase in the number of osteoblasts results in a
      concomitant increase in the hematopoietic population, indicating that the
      osteoblasts and the endosteal niche are key components of HSC maintenance. On the
      other hand, impaired function of the vascular niche compromises the endosteal
      niche's ability to support hematopoiesis. These fascinating discoveries indicate
      that there are strong ties between bone marrow inhabitants within the confines of
      the bone marrow itself. When these ties fail, niche-niche communication suffers
      and results in reduced bone formation, enfeebled hematopoiesis and unrestrained
      HSC migration through blood circulation. This study focused on the extraordinary
      homeostatic equilibrium and function of both bone and immune cells within the
      spatially defined microenvironment of bone marrow. But how important is the
      anatomically outlined scenery in which the bone marrow entity supports and hosts
      the hematopoietic elements? 

PMID- 25563566
TI  - History and conceptual problems of the relationship between obsessions and
      hallucinations.
AB  - Contemporary psychiatric nomenclature defines schizophrenia (SCZ) and obsessive
      compulsive disorder (OCD) as distinct disease entities characterized by non
      overlapping diagnostic criteria. Nevertheless, a complex association between SCZ
      and OCD exists on the psychopathological level. And although the relationship
      between obsessions and delusions has been widely studied and discussed, the
      relationship between obsessions and hallucinations has not received the same
      attention. This article presents an historical overview of the studies on the co
      occurrence of obsessions and hallucinations. We also analyze the clinical
      significance of this overlap, as discussed in the early descriptions of these
      phenomena in the nineteenth century and continuing through the most recent,
      contemporary conceptualizations. In clinical practice today, we may encounter
      both SCZ patients with typical ego-dystonic obsessive-compulsive symptoms and SCZ
      patients affected by obsessions that intertwine with psychotic symptoms,
      generating complex psychopathological syndromes (e.g. "obsessive
      hallucinations"). A further complication is that some OCD patients show
      perceptual disturbances. Taking into consideration the possible coexistence of
      obsessive-compulsive symptoms and psychotic symptoms is crucial for proper
      diagnosis, prognosis, and treatment. Further investigations are required to fully
      evaluate the psychopathological interrelationships between obsessions and
      hallucinations. 

PMID- 25563567
TI  - Moral engagement, combat trauma, and the lure of psychiatric dualism: why
      psychiatry is more than a technical discipline.
AB  - Psychiatry is not only a technical discipline concerned with matching appropriate
      means to pre-specified ends; it is also a discipline of moral engagement and
      discernment in which clinicians and patients explore the ends that patients will
      pursue. Moral engagement is intrinsic to psychiatric practice, particularly when
      psychiatrists engage issues such as combat trauma in which patients' moral self
      evaluations are relevant to the perpetuation of psychological distress. Relative
      to technical models of practice, however, the space of moral engagement and
      discernment conveys risk for psychiatrists as it is less "scientific," more prone
      to exploitation and abuse, and the occasion for social-political critiques of
      psychiatry. Three prevalent forms of psychiatric dualism, each manifest in the
      care of combat veterans, seem to allow psychiatrists to avoid this contested
      moral space: dualism of the self and the self's body, dualism of the self and the
      self's quantifiable experience and behavior, and dualism of the self and the
      self's "values." Each of these dualisms is alluring but ultimately unable to
      protect psychiatrists from the space of moral engagement. Psychiatrists must
      rather cultivate practices for inhabiting that space in a morally transparent,
      self-questioning, and responsible way. 

PMID- 25563568
TI  - Perfect storm: illness, stress, and culture in a foreign land.

PMID- 25563565
TI  - Genetic determinants of depression: recent findings and future directions.
AB  - LEARNING OBJECTIVES: After participating in this activity, learners should be
      better able to: 1. Evaluate current evidence regarding the genetic determinants
      of depression 2. Assess findings from studies of gene-environment interaction 3.
      Identify challenges to gene discovery in depression Depression is one of the most
      prevalent, disabling, and costly mental health conditions in the United States
      and also worldwide. One promising avenue for preventing depression and informing
      its clinical treatment lies in uncovering the genetic and environmental
      determinants of the disorder as well as their interaction (G * E). The
      overarching goal of this review article is to translate recent findings from
      studies of genetic association and G * E related to depression, particularly for
      readers without in-depth knowledge of genetics or genetic methods. The review is
      organized into three major sections. In the first, we summarize what is currently
      known about the genetic determinants of depression, focusing on findings from
      genome-wide association studies (GWAS). In the second section, we review findings
      from studies of G * E, which seek to simultaneously examine the role of genes and
      exposure to specific environments or experiences in the etiology of depression.
      In the third section, we describe the challenges to genetic discovery in
      depression and promising strategies for future progress.

PMID- 25563570
TI  - Better sorry than safe: Making a Plan B reduces effectiveness of implementation
      intentions in healthy eating goals.
AB  - OBJECTIVE: Implementation intentions (if-then plans) are helpful to health
      behaviour change. As these plans specify only one goal-directed behaviour for one
      specific situation, however, their effectiveness may be limited when a planned
      behaviour is impossible to execute in situ. The present research examines whether
      and how planning more than one goal-directed response for the same situation
      ('making a Plan B') affects successful self-regulation of eating behaviour.
      DESIGN AND MAIN OUTCOME MEASURES: In Study 1, participants formulated either one
      or two plans, after which a lexical decision task was administered to assess
      association strength between the if-part and the then-part(s). In Study 2, the
      effect of making one, two or no plan(s) was assessed on actual eating behaviour,
      after which a Stroop task measured cognitive load as an additional explanatory
      mechanism. RESULTS: Study 1 revealed that making a Plan B disrupts the creation
      of strong if-then associations during plan formation. Study 2 showed that making
      a Plan B yields increased unhealthy food intake compared to making one or no
      plan, and induces greater cognitive load during plan enactment. CONCLUSION:
      Making a Plan B interferes with essential cognitive processes during different
      stages of planning, leading to an increased likelihood of self-regulatory
      failure.

PMID- 25563571
TI  - Type I dual left anterior descending coronary artery anomaly presenting with non
      ST-segment elevation myocardial infarction, initially mimicking normal coronary
      angiogram.

PMID- 25563572
TI  - Effect of surface microstructure on electrochemical performance of garnet solid
      electrolytes.
AB  - Cubic garnet phases based on Al-substituted Li7La3Zr2O12 (LLZO) have high ionic
      conductivities and exhibit good stability versus metallic lithium, making them of
      particular interest for use in next-generation rechargeable battery systems.
      However, high interfacial impedances have precluded their successful utilization
      in such devices until the present. Careful engineering of the surface
      microstructure, especially the grain boundaries, is critical to achieving low
      interfacial resistances and enabling long-term stable cycling with lithium metal.
      This study presents the fabrication of LLZO heterostructured solid electrolytes,
      which allowed direct correlation of surface microstructure with the
      electrochemical characteristics of the interface. Grain orientations and grain
      boundary distributions of samples with differing microstructures were mapped
      using high-resolution synchrotron polychromatic X-ray Laue microdiffraction. The
      electrochemical characteristics are strongly dependent upon surface
      microstructure, with small grained samples exhibiting much lower interfacial
      resistances and better cycling behavior than those with larger grain sizes. Low
      area specific resistances of 37 Omega cm(2) were achieved; low enough to ensure
      stable cycling with minimal polarization losses, thus removing a significant
      obstacle toward practical implementation of solid electrolytes in high energy
      density batteries. 

PMID- 25563573
TI  - Regulatory motifs on ISWI chromatin remodelers: molecular mechanisms and kinetic
      proofreading.
AB  - Recently, kinetic proofreading scenarios have been proposed for the regulation of
      chromatin remodeling, first on purely theoretical grounds (Blossey and Schiessel
      2008 HFSP J. 2 167-70) and deduced from experiments on the ISWI/ACF system
      (Narlikar 2010 Curr. Opin. Chem. Biol. 14 660). In the kinetic proofreading
      scenario of chromatin remodeling, the combination of the recognition of a histone
      tail state and ATP-hydrolysis in the remodeler motor act together to select (i.e.
      proofread) a nucleosomal substrate. ISWI remodelers have recently been shown to
      have an additional level of regulation as they contain auto-inhibitory motifs
      which need to be inactivated through an interaction with the nucleosome. In this
      paper we show that the auto-regulatory effect enhances substrate recognition in
      kinetic proofreading. We further report some suggestive additional insights into
      the molecular mechanism underlying ISWI-autoregulation. 

PMID- 25563569
TI  - Preclinical perspectives on posttraumatic stress disorder criteria in DSM-5.
AB  - Posttraumatic stress disorder (PTSD) now sits within the newly created "Trauma-
      and Stressor-Related Disorders" section of the Diagnostic and Statistical Manual
      of Mental Disorders (fifth edition; DSM-5). Through the refinement and expansion
      of diagnostic criteria, the DSM-5 version better clarifies the broad and
      pervasive effects of trauma on functioning, as well as the impact of development
      on trauma reactions. Aggressive and dissociative symptoms are more thoroughly
      characterized, reflecting increasing evidence that reactions to trauma often
      reach beyond the domains of fear and anxiety (these latter domains were
      emphasized in DSM-IV). These revised criteria are supported by decades of
      preclinical and clinical research quantifying traumatic stress-induced changes in
      neurobiological and behavioral function. Several features of the DSM-5 PTSD
      criteria are similarly and consistently represented in preclinical animal models
      and humans following exposure to extreme stress. In rodent models, for example,
      increases in anxiety-like, helplessness, or aggressive behavior, along with
      disruptions in circadian/neurovegetative function, are typically induced by
      severe, inescapable, and uncontrollable stress. These abnormalities are prominent
      features of PTSD and can help us in understanding the pathophysiology of this and
      other stress-associated psychiatric disorders. In this article we examine some of
      the changes to the diagnostic criteria of PTSD in the context of trauma-related
      neurobiological dysfunction, and discuss implications for how preclinical data
      can be useful in current and future clinical conceptualizations of trauma and
      trauma-related psychiatric disorders. 

PMID- 25563574
TI  - On the interplay between geometrical structure and magnetic anisotropy: a
      relativistic density-functional study of mixed Pt-Co and Pt-Fe trimers and
      tetramers in the gas-phase and supported on graphene.
AB  - The structural and magnetic properties of mixed Pt-Co and Pt-Fe trimers and
      tetramers in the gas-phase and supported on a free-standing graphene layer have
      been calculated using density-functional theory. The influence of the strong
      magnetic moments of the 3d atoms on the Pt atoms and the influence of the strong
      spin-orbit coupling contributed by the Pt atoms on the 3d atoms have been studied
      in detail. All mixed trimers form isocele triangles in the gas-phase. On a
      graphene layer the structure is influenced by the strong binding of the 3d atoms,
      leading to an asymmetric configuration for Pt-rich and more symmetric structures
      for 3d-rich clusters. The magnetic anisotropy energy defined as the energy
      difference for easy and hard magnetization directions varies between 5 and 13
      meV/atom for the free trimers, but is strongly reduced to values between 0.7 and
      6.6 meV/atom for the graphene-supported clusters. The saddle-point energy
      representing the barrier against magnetization reversal is on average 3 meV/atom
      for free trimers, it is reduced to 2 meV/atom for the more symmetric PtCo(Fe)(2)
      clusters, and to only about 0.3 meV/atom for the asymmetric Pt(2)Co(Fe) cluster
      on graphene. For the mixed tetramers the strong magnetism stabilizes a flat
      geometric structure, except for Pt(3)Co which forms a distorted trigonal pyramid.
      The geometry of the graphene-supported tetramers is very different due to the
      requirement of a good match to the substrate. Large magnetic anisotropy energies
      are found for free Pt(3)Co where the change of the magnetization direction also
      induces a transition from a high- to a low-moment magnetic isomer. For all other
      free tetramers the magnetic anisotropy energy ranges between 3 to 5 meV/atom
      only, it is further reduced to 0.4 to 3.8 meV/atom for the graphene-supported
      tetramers. The reduction is strongest for Pt(3)Fe/graphene because of the
      asymmetric structure of the adsorption complex. The barriers against
      magnetization reversal range between only 0.3 meV/atom for Pt(3)Fe/graphene and
      about 3 meV/atom for PtFe(3) and Pt(3)Co. Altogether our results demonstrate a
      strong correlation between the geometric and magnetic degrees of freedom and the
      necessity to base investigations of the magnetic anisotropy of nanostructures on
      a simultaneous optimization of the total energy with respect to all geometric and
      magnetic parameters.

PMID- 25563575
TI  - Clinical and microbiological features of patients admitted to the intensive care
      unit with nursing and healthcare-associated pneumonia.
AB  - OBJECTIVE: To evaluate clinical and microbiological features in patients with
      nursing and healthcare-associated pneumonia (NHCAP), admitted to the intensive
      care unit (ICU). METHODS: Demographic, clinical and microbiological data were
      retrospectively reviewed from patients with NHCAP admitted to a respiratory ICU.
      Patients were categorized into one of four NHCAP groups: (A) residence in a long
      term nursing-home setting or healthcare home; (B) hospital discharge in the
      preceding 90 days; (C) elderly or physically disabled patients who stay at home
      but require healthcare; (D) continuously receiving outpatient endovascular
      therapy including chronic dialysis, anticancer drugs, and immunosuppressants.
      Pneumonia severity index (PSI), CURB-65, duration of ICU stay and 30-day
      mortality were evaluated. RESULTS: Out of 428 patients reviewed (male, 67.1%;
      mean age, 71.2 +/- 11.9 years), 30-day mortality was 25.5%, and duration of ICU
      stay was 13.8 +/- 13.3 days. Mortality rate was not significantly different
      between the four NHCAP groups; duration of ICU stay was significantly longer in
      groups C and D. PSI score, serum HCO3(-) level, duration of ICU stay, extended
      spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae and multidrug
      resistant (MDR) Acinetobacter baumannii were significantly associated with 30-day
      mortality. CONCLUSION: ESBL-producing K. pneumoniae, MDR A. baumannii and PSI
      score should be considered in ICU patients with NHCAP.

PMID- 25563576
TI  - Factors Associated With Exposure to Violent or Degrading Pornography Among High
      School Students.
AB  - The purpose of this study was to analyze pornography exposure in a sample of 702
      Italian adolescents (46% males; mean age = 18.2, SD = 0.8). Among male students,
      11% were not exposed, 44.5% were exposed to nonviolent material, and 44.5% were
      exposed to violent/degrading material. Among female students, 60.8% were not
      exposed, 20.4% were exposed to nonviolent material, and 18.8% were exposed to
      violent/degrading material. Among males, adjusted odds ratio (AdjOR) of exposure
      to violent/degrading pornography were higher if using alcohol, having friends who
      sell/buy sex, and taking sexual pictures. Females who were victims of family
      violence, attending technical/vocational schools, and taking sexual pictures had
      higher AdjOR of watching violent pornography; smoking and having friends who
      sell/buy sex were associated with both nonviolent and violent/degrading exposure.
      Exposure to violent/degrading pornography is common among adolescents, associated
      with at-risk behaviors, and, for females, it correlates with a history of
      victimization. School nurses have a pivotal role in including discussions about
      pornography in interventions about relationships, sexuality, or violence. 

PMID- 25563577
TI  - Perspectives of physicians regarding screening patients at risk of hepatocellular
      carcinoma.
AB  - BACKGROUND AND AIMS: Screening patients at risk for hepatocellular carcinoma
      (HCC) facilitates early detection of disease, with improved outcome. The most
      common causes of HCC include chronic viral hepatitis infection-namely hepatitis
      B, hepatitis C, and cirrhosis. The aim of this study was to assess the awareness
      of screening among physicians involved in the management of patients at risk for
      HCC. METHODS: Three hundred physicians from three academic centers were invited
      to participate in a mailed survey questionnaire. The main outcome measure was
      physicians' knowledge of the current HCC screening guidelines. Demographic and
      clinical variables were obtained from the survey questionnaire. RESULTS: A total
      of 177 (59.0%) out of the 300 invited physicians responded to the survey
      questionnaire, including faculty members (n = 129), residents (n = 46), and
      fellows (n = 2). The specialty areas of the responding physicians were internal
      medicine (62.1%), family medicine (16.4%), gastroenterology (15.3%), oncology
      (3.4%) and others (2.8%). The number of physicians who performed HCC screening in
      patients with cirrhosis secondary to chronic hepatitis B and chronic hepatitis C
      infection were 163 (92.1%) and 167 (94.4%), respectively; 35.0% of them used
      alpha-fetoprotein (AFP) every 6 months, while 22.0% used imaging modalities every
      6 months to screen for HCC. Further, 22 physicians (12.4%) did not check for
      serum AFP levels and 33 (18.6%) never used imaging to screen for HCC. CONCLUSION:
      The majority of the participating physicians screen high-risk patients for HCC.
      However, the most appropriate modality of screening (i.e. imaging) is not
      employed by most physicians and there is greater reliance on AFP levels.

PMID- 25563578
TI  - Diagnostic efficacy of parametric clearance images in detection of renal scars in
      children with recurrent urinary tract infections.
AB  - OBJECTIVE: Static renal scintigraphy with Tc-99m dimercaptosuccinic acid (DMSA)
      is considered a scintigraphic gold standard in detection of post-inflammatory
      renal scars. Reports on usefulness of conventional summed (SUM) Tc-99 m
      mercaptoacetyltriglycine (MAG3) or Tc-99m ethylene dicysteine (EC) dynamic
      scintigraphic images in detection of renal scarring are ambiguous and some
      authors emphasize low sensitivity of this method. The work aimed at assessment of
      a diagnostic efficacy of parametric clearance images (PAR) generated from a
      dynamic renal scintigraphy in detection of renal scars. METHODS: A study group
      consisting of 80 children (56 girls, 24 boys, age 5-18 years) with recurrent
      urinary tract infections (UTI) and documented one to five incidents of APN-28
      children, and with recurrent UTI of the lower part of the urinary tract only-52
      children. Altogether 160 kidneys were evaluated. Static renal Tc-99m DMSA SPECT
      scintigraphy and after 2-4 days Tc-99m EC dynamic renal scintigraphy were
      performed in every patient not earlier than 6 months after the last documented
      incident of UTI. PAR images generated from a dynamic renal scintigraphy acquired
      between 40 and 140 s. generated by in-house developed software and SUM images
      obtained in the same time period were compared with a reference Tc-99m DMSA SPECT
      study. RESULTS: For all kinds of images (SPECT, PAR and SUM), high indices of
      reproducibility were obtained-89 % (kappa = 0.80), 88 % (kappa = 0.78) and 89 %
      (kappa = 0.73). Agreement in a Howard scale of a reference method (SPECT) with
      PAR and SUM methods amounted to 83 and 64 %, respectively (p = 0.004).
      Sensitivity and accuracy of PAR method as compared with SUM method were
      significantly higher: 89 vs. 49 % (p < 0.0001) and 88 vs. 73 % (p = 0.002), and
      specificity was slightly lower: 88 vs. 93 % (p = 0.043). SPECT and PAR methods
      revealed higher incidence of renal scars than a SUM method in patients with
      documented incident(s) of APN-64, 68 and 39 %, p = 0.009 and 0.008, respectively.
      CONCLUSION: PAR images generated from a dynamic renal scintigraphy improved
      sensitivity of detection of renal scars as compared with SUM images, providing a
      high reproducibility and diagnostic efficacy, similar to that of Tc-99m DMSA, in
      detection of post-inflammatory renal scarring.

PMID- 25563580
TI  - Impact of serum estradiol levels on the implantation rate of cleavage stage
      cryopreserved-thawed embryos transferred in programmed cycles with exogenous
      hormonal replacement.
AB  - PURPOSE: To investigate the impact of late follicular phase serum estradiol (E2)
      levels on implantation and pregnancy outcomes of cleavage stage
      cryopreserved/thawed embryos transferred in programmed cycles with exogenous
      hormonal replacement. METHODS: Retrospective cohort analysis of IVF patients with
      transfer of cryopreserved-thawed day-3 embryos in E2 and progesterone (P4)
      supplemented cycles (n = 208 cycles). MAIN OUTCOME MEASURES: implantation and
      pregnancy rates according to late follicular phase serum E2 levels and early
      secretory phase E2/P4 ratios. RESULTS: Logistic regression performed for embryo
      implantation and for pregnancy outcome in relation to E2 (day 15), P4 (day 15 and
      16), before (crude analysis) and after adjustment (adjusted analysis) for
      baseline characteristics (including age, BMI, serum basal cycle day 3 FSH levels,
      embryo quality, endometrial lining thickness) showed no significant association.
      Similarly, ROC analysis showed no impact of cycle day 16 E2/P4 ratio.
      CONCLUSIONS: Neither late follicular phase serum E2 nor the early E2/P4 ratio
      were able to predict implantation or pregnancy outcome of day-3 cryopreserved
      thawed embryos transferred in artificially programmed cycles.

PMID- 25563579
TI  - Adverse prognostic impact of perioperative allogeneic transfusion on patients
      with stage II/III gastric cancer.
AB  - BACKGROUND: Allogeneic blood transfusions (BTFs) are sometimes required for
      radical gastrectomy with regional lymph node dissection for advanced gastric
      cancer (GC). The prognostic impact of perioperative BTF in GC is controversial.
      METHODS: Clinical data were collected retrospectively from 250 consecutive
      patients who underwent curative gastric resection for stage II/III GC. The
      prognostic impact of BTF on patient survival was evaluated. Subgroup analysis was
      performed according to units of blood transfused, timing of BTF, type of
      gastrectomy, splenectomy, intraoperative estimated blood loss, and year of
      surgery. RESULTS: Fifty-seven (22.8%) patients underwent perioperative BTF.
      Patients who received BTF experienced a significantly shorter disease-specific
      survival after curative surgery, and multivariable analysis identified
      perioperative BTF as an independent prognostic factor for cancer-related death
      (hazard ratio, 1.80; 95% confidence interval, 1.05-3.02; p = 0.032). The BTF
      group experienced significantly lower recurrence-free survival rate and a higher
      rate of initial peritoneal recurrence. The amount of blood cells transfused had
      less impact on prognosis. Pre- or postoperative BTF without intraoperative BTF
      had limited influence on postoperative prognosis. Prognosis of patients was
      affected by splenectomy. Even when intraoperative blood loss exceeded 800 ml, the
      prognosis of the non-BTF group was more favorable. The prognostic impact of BTF
      became less clear after introduction of adjuvant chemotherapy with S-1.
      CONCLUSIONS: BTF was an independent prognostic factor in patients with stage
      II/III GC after curative gastrectomy. To improve prognosis, BTF should be avoided
      when possible, particularly during surgery.

PMID- 25563582
TI  - Back pain: musculoskeletal or something else?

PMID- 25563583
TI  - Evaluation of aspirin resistance and the presence of unstable carotid plaque in
      patients undergoing carotid endarterectomy.
AB  - BACKGROUND: Antiplatelet therapy using low dose acetylsalicylic acid (ASA) is
      routinely recommended in patients undergoing surgical or endovascular treatment
      of carotid artery disease. Despite this treatment, a significant proportion of
      postoperative complications may result from inadequate response to antiplatelet
      therapy which may contribute to the development of unstable plaques. AIM:
      Assessment of correlation between ASA resistance and the presence of unstable
      carotid plaque in patients after carotid endarterectomy. METHODS: We studied 66
      patients (27 women and 39 men) aged 41-80 years who were operated for carotid
      stenosis. All patients received ASA (75 mg once daily) in the pre- and
      perioperative period. Measurements of platelet reactivity were performed using
      the PFA-100 platelet analyser at the second day after the operation. Plaque
      stability was evaluated using a computer analysis system based on the greyscale
      median method. The patients were divided into two groups, showing good response
      to ASA or ASA-resistant. RESULTS: ASA resistance was identified in 19 (32%)
      patients. In multivariate logistic regression analysis, unstable plaque showed a
      borderline correlation with ASA resistance (p = 0.051). CONCLUSIONS: 1.
      Prevalence of increased platelet reactivity despite ASA treatment (ASA
      resistance) in patients treated surgically for carotid artery disease is high,
      suggesting a possibility of ineffective antiplatelet therapy. 2. A modest
      correlation between abnormal platelet response during treatment with ASA and the
      presence of unstable plaques suggests that these two phenomena may coexist but we
      were unable to show a clear association between them.

PMID- 25563581
TI  - microRNA profiling in three main stages during porcine spermatogenesis.
AB  - BACKGROUND: Spermatogenesis is an intricate biological event wherein an
      undifferentiated spermatogonium develops into mature sperms. MicroRNAs are a type
      of single strand small non-coding RNA molecule and are implicated in the
      regulation of many crucial pathways during cell proliferation, apoptosis, and
      differentiation. METHOD: Here, we present a comprehensive comparison of miRNA
      expression profiling in three main stages during porcine spermatogenesis using
      high-throughput sequencing. RESULTS: We built three small RNA libraries for the
      testis, the epididymis and the ejaculated sperm from a Landrace boar, and in
      total obtained 3821 precursor hairpins encoding for 4761 mature miRNAs, of which
      23 are miRNA*. Notably, 940 precursor miRNAs produced both the 5'- and 3'-
      strands as sister pairs, indicating the distinctive expression patterns of germ
      cell miRNAs. Additionally, 418 out of 710 co-expressed miRNAs were identified as
      being differentially expressed between libraries (P < 0.001). Apart from the
      sexual specific X chromosome, many miRNAs were found to be located on chromosome
      12, which may play potential roles in spermatogenesis according to the result of
      synteny analysis with human and mouse. The Gene Ontology and KEGG pathway
      analysis revealed that the target genes of co-expressed miRNAs were highly
      involved in the cell cycle process, metal ion binding, modification of plasma
      membrane, and the p53 signal pathway.

PMID- 25563585
TI  - Mitochondrial induction as a potential radio-sensitizer in lung cancer cells - a
      short report.
AB  - INTRODUCTION: Lung cancer is the leading cause of cancer death. Radiation therapy
      plays a key role in its treatment. Ionizing radiation induces cell death through
      chromosomal aberrations, which trigger mitotic catastrophe and apoptosis.
      However, many lung cancer patients show resistance to radiation. Dichloroacetate
      (DCA) is a small molecule that can promote mitochondrial activation by increasing
      the influx of pyruvate. Here, we tested whether DCA may increase the sensitivity
      of non-small cell lung cancer (NSCLC) cells to radiation through this mechanism.
      METHODS: Two representative NSCLC cell lines (A549 and H1299) were tested for
      their sensitivity to radiation with and without pre-exposure to DCA. The
      treatment efficacy was evaluated using a clonogenic survival assay. An
      extracellular flux analyzer was used to assess the effect of DCA on cellular
      oxygen consumption as a surrogate marker for mitochondrial activity. RESULTS: We
      found that DCA increases the oxygen consumption rate in both A549 and H1299 cells
      by 60% (p = 0.0037) and 20% (p = 0.0039), respectively. Pre-exposure to DCA one
      hour before radiation increased the cytotoxic death rate 4-fold in A549 cells (55
      to 13%, p = 0.004) and 2-fold in H1299 cells (35 to 17%, p = 0.28) respectively,
      compared to radiation alone. CONCLUSION: Mitochondrial induction by DCA may serve
      as a radio-sensitizer in non-small cell lung cancer.

PMID- 25563584
TI  - Early exercise after spinal cord injury ('Switch-On'): study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Spinal cord injury (SCI) leads to a profound muscular atrophy, bone
      loss and bone fragility. While there is evidence that exercising paralysed
      muscles may lead to reversal of muscle atrophy in the chronic period after SCI,
      there is little evidence that exercise can prevent muscle changes early after
      injury. Moreover, whether exercise can prevent bone loss and microarchitectural
      decay is not clear. METHODS/DESIGN: A multi-centre, parallel group, assessor
      blinded randomised controlled trial will be conducted. Fifty participants with
      acute spinal cord injury will be recruited from four SCI units in Australia and
      New Zealand. Participants will be stratified by site and AIS status and
      randomised to an experimental or control group. Experimental participants will
      receive a 12-week programme of functional electrical stimulation (FES)-assisted
      cycling. Control participants will receive a 12-week programme of passive
      cycling. The primary outcome is muscle cross-sectional area of the thigh and calf
      measured using magnetic resonance images (MRI) of the leg. Secondary outcomes
      include serum biomarkers of SCI osteoporosis (sclerostin, P1NP and beta-CTX),
      markers of immune function (IL-6, IL-10, FGF2, INF-gamma, TNF-alpha),
      neurological function, body composition, depression and quality of life. Leg MRIs
      will be measured by a single blinded assessor based in Melbourne. Serum samples
      will be analysed in a central laboratory. All other characteristics will be
      measured at baseline and 12 weeks by blinded and trained assessors at each site.
      The first participant was randomised on 27 November 2012. DISCUSSION: The results
      of this trial will determine the relative effectiveness of a 12-week programme of
      FES-assisted cycling versus passive cycling in preventing muscle atrophy and
      maintaining skeletal integrity after spinal cord injury. TRIAL REGISTRATION:
      ACTRN12611001079932 (18 October 2011).

PMID- 25563587
TI  - A 10-year experience of totally extraperitoneal endoscopic repair for adult
      inguinal hernia.
AB  - PURPOSE: Laparoscopic surgery is fast becoming the treatment of choice for
      inguinal hernia. By reviewing our 10-year experience of performing totally
      extraperitoneal repair (TEP), we sought to establish its clinical significance in
      the treatment of adult inguinal hernia. METHODS: We reviewed retrospectively the
      clinical records of patients who underwent TEP for adult inguinal hernia between
      January 2003 and December 2012. RESULTS: None of the 303 patients with adult
      primary or recurrent inguinal hernia in our study needed TEP converted to other
      procedures or suffered serious complications during the procedure. A significant
      difference was noted in the operation time between direct (n = 32) vs indirect (n
      = 128) hernias in the primary unilateral inguinal hernia group (91 +/- 27 vs 80
      +/- 32 min, p = 0.033) and between direct/direct (n = 31) vs indirect/indirect (n
      = 24) hernias (136 +/- 58 vs 89 +/- 24 min, p = 0.01) in the primary bilateral
      inguinal hernia group. The only postoperative complications recorded were four
      cases of hernia recurrence (1.3 %) and one case of chronic pain (0.3 %).
      CONCLUSIONS: The results obtained for TEP over 10 years support this as a
      promising procedure for the treatment of adult inguinal hernia.

PMID- 25563588
TI  - The clinical relevance of the Fong and the Nordlinger scores in the era of
      effective neoadjuvant chemotherapy for colorectal liver metastasis.
AB  - PURPOSE: The clinical risk scores (CRSs) of Fong and Nordlinger are used to
      predict the outcome of patients with colorectal liver metastases (CRLMs). This
      study investigated whether CRSs could predict the overall survival of patients
      with CRLM treated with or without neoadjuvant chemotherapy prior to resection.
      METHODS: Patients with CRLM undergoing liver resection were analyzed
      retrospectively. The primary outcome measure was overall survival with vs.
      without neoadjuvant chemotherapy. RESULTS: Between August 2002 and October 2011,
      300 patients underwent liver resection for CRLMs at a large university hospital
      in Germany. Group A comprised 117 patients who received neoadjuvant chemotherapy
      and group B comprised 71 patients who did not. The Fong score predicted overall
      survival for patients who did not receive chemotherapy (p = 0.02), but not for
      those treated with chemotherapy (p = 0.69). The Nordlinger score was not
      predictive for either of the groups (p = 0.71 vs. p = 0.08 for groups A and B,
      respectively). Subgroup analysis of the Nordlinger score identified better
      overall survival in the high-risk group treated with chemotherapy (p = 0.05).
      Multivariate analysis identified a resection margin of <1 cm [OR 0.622 (95% CI:
      0.17-2.31); p = 0.044], age >60 years [OR 0.535 (95% CI: 0.16-1.77); p = 0.022]
      and number of metastases >4 [OR 0.189 (95% CI: 0.06-0.61); p = 0.018] as
      independent prognostic factors for overall survival. CONCLUSION: Thus, CRSs were
      not reliable prognostic tools for patients treated with neoadjuvant chemotherapy
      before liver resection in this analysis.

PMID- 25563589
TI  - Short-term surgical outcomes of reduced port surgery for esophageal achalasia.
AB  - PURPOSE: To clarify the feasibility and utility of reduced port surgery (RPS) for
      achalasia. METHODS: Between September 2005 and June 2013, 359 patients with
      esophageal achalasia, excluding cases of reoperation, underwent laparoscopic
      Heller myotomy and Dor fundoplication (LHD) according to our clinical pathway.
      Three-hundred and twenty-seven patients underwent LHD with five incisions
      (conventional approach), while the other 32 patients underwent RPS, including
      eight via SILS. The clinical data were collected in a prospective fashion and
      retrospectively reviewed. We selected 24 patients matched for gender, age and
      morphologic type with patients in the RPS group from among the 327 patients (C
      group). The surgical outcomes were compared between the C and RPS groups.
      RESULTS: There were no significant differences between the two groups in the
      duration of symptoms, dysphagia score, chest pain score, shape of the distal
      esophagus and esophageal clearance. The operative time was significantly longer
      in the RPS group than in the C group (p < 0.001). There were no significant
      differences between the two groups in the length of postoperative hospital stay
      or rates of bleeding, mucosal injury of the esophagus and/or stomach and
      postoperative complications. The symptom scores significantly improved after
      surgery in both groups (p < 0.001). Furthermore, there were no significant
      differences between the C group and RPS group in terms of the postoperative
      symptom scores or satisfaction scores after surgery. CONCLUSIONS: The surgical
      outcomes of RPS for achalasia are comparable to those obtained with the
      conventional method.

PMID- 25563586
TI  - Molecular basis of chronic lymphocytic leukemia diagnosis and prognosis.
AB  - BACKGROUNDS: Chronic lymphocytic leukemia (CLL) is the most common type of
      leukemia in adults and is characterized by a clonal accumulation of mature
      apoptosis-resistant neoplastic cells. It is also a heterogeneous disease with a
      variable clinical outcome. Here, we present a review of currently known
      (epi)genetic alterations that are related to the etiology, progression and chemo
      refractoriness of CLL. Relevant literature was identified through a PubMed search
      (1994-2014) of English-language papers using the terms CLL, signaling pathway,
      cytogenetic abnormality, somatic mutation, epigenetic alteration and micro-RNA.
      RESULTS: CLL is characterized by the presence of gross chromosomal abnormalities,
      epigenetic alterations, micro-RNA expression alterations, immunoglobulin heavy
      chain gene mutations and other genetic lesions. The expression of unmutated
      immunoglobulin heavy chain variable region (IGHV) genes, ZAP-70 and CD38
      proteins, the occurrence of chromosomal abnormalities such as 17p and 11q
      deletions and mutations of the NOTCH1, SF3B1 and BIRC3 genes have been associated
      with a poor prognosis. In addition, mutations in tumor suppressor genes, such as
      TP53 and ATM, have been associated with refractoriness to conventional
      chemotherapeutic agents. Micro-RNA expression alterations and aberrant
      methylation patterns in genes that are specifically deregulated in CLL, including
      the BCL-2, TCL1 and ZAP-70 genes, have also been encountered and linked to
      distinct clinical parameters. CONCLUSIONS: Specific chromosomal abnormalities and
      gene mutations may serve as diagnostic and prognostic indicators for disease
      progression and survival. The identification of these anomalies by state-of-the
      art molecular (cyto)genetic techniques such as fluorescence in situ hybridization
      (FISH), comparative genomic hybridization (CGH), single nucleotide polymorphism
      (SNP) microarray-based genomic profiling and next-generation sequencing (NGS) can
      be of paramount help for the clinical management of these patients, including
      optimal treatment design. The efficacy of novel therapeutics should to be tested
      according to the presence of these molecular lesions in CLL patients.

PMID- 25563590
TI  - EGFR Transactivation by Peptide G Protein-Coupled Receptors in Cancer.
AB  - Lung cancer kills approximately 1.3 million citizens in the world annually. The
      tyrosine kinase inhibitors (TKI) erlotinib and gefitinib are effective anti-tumor
      agents especially in lung cancer patients with epidermal growth factor receptor
      (EGFR) mutations. The goal is to increase the potency of TKI in lung cancer
      patients with wild type EGFR. G protein-coupled receptors (GPCR) transactivate
      the wild type EGFR in lung cancer cells. The GPCR can be activated by peptide
      agonists causing phosphatidylinositol turnover or stimulation of adenylylcyclase.
      Recently, nonpeptide antagonists were found to inhibit the EGFR transactivation
      caused by peptides. Nonpeptide antagonists for bombesin (BB), neurotensin (NTS)
      and cholecystokinin (CCK) inhibit lung cancer growth and increase the
      cytotoxicity of gefitinib. The results suggest that GPCR transactivation of the
      EGFR may play an important role in cancer cell proliferation. 

PMID- 25563591
TI  - Oxidative stress and neurodegenerative diseases: a neurotrophic approach.
AB  - Neurotrophins are important neurotrophic factors involved in the survival,
      differentiation and function of a wide variety of neuron populations. A common
      feature for most neurotrophins is that they are synthesized as precursor proteins
      (pro-neurotrophins) that upon being processed by proteolysis render the mature
      active form responsible for most of their trophic functions. However, some of the
      pro-neurotrophin form of these proteins, such as the precursor form of NGF (pro
      NGF), have been shown to induce opposite effects and trigger apoptosis on neurons
      through the p75NTR receptor. This suggests that the balance between the levels of
      proneurotrophin and neurotrophin must be tightly controlled. In this context, it
      has been shown that in conditions of oxidative stress due for instance to aging
      or the development of some neurodegenerative disease, neurotrophins are
      oxidatively modified at least by advanced glycation/lipoxidation end products
      (AGE/ALEs) which makes pro-NGF refractary to be processed. The lack of maturation
      and the imbalance in favor of the precursor form may change the pattern of active
      signaling pathways towards cell death, thus exacerbating the deleterious
      alterations, for instance during the development of neurodegenerative diseases.
      Besides that, AGE/ALEs also induce the processing of the pro-NGF receptor p75NTR
      by alpha- secretase which is followed by the processing by gamma -secretase and
      the release of the intracellular domain of p75NTR (p75NTRICD). Once cleaved,
      p75NTRICD recruits two intracellular interactors, NRIF and TRAF6, which allows
      NRIF phosphorylation by JNK. The phosphorylated form of NRIF then translocates to
      the nucleus and induces the expression of pro-apoptotic proteins. In this chapter
      we will summarize the mechanisms by which ROS- induce protein modifications,
      which proteins are susceptible to be modified, how these modifications affect
      function and signaling and, finally, how they can be related to neurodegenerative
      diseases. 

PMID- 25563592
TI  - The Effect of Krill Oil and n-3 Polyunsaturated Fatty Acids on Human Osteosarcoma
      Cell Proliferation and Migration.
AB  - BACKGROUND: Osteosarcoma (OS) is a neoplastic condition afflicting mostly the
      young, as the lesion usually occurs in areas of bone growth with tumour cells
      metastasising to the lungs in advanced disease. There is no real cure for the
      disease, with conventional drugs causing side-effects that decrease the quality
      of life of sufferers. Newer and safer drugs are needed, and one avenue is to use
      natural compounds that can stunt the growth of the tumour. OBJECTIVE: In this
      study, two such biological entities were evaluated: krill oil and fish oil. Human
      OS cells were exposed to krill oil, fish oil, EPA and DHA in time-course assays
      lasting up to 72h. RESULTS: Krill oil inhibited 23, 50 and 64% of cell
      proliferation at 24, 48 and 72h respectively, while fish oil resulted in no
      significant changes although an increase was observed at 24h. Interestingly EPA
      and DHA promoted OS cell proliferation and migration in this neoplasia. The
      inhibitory effect of krill oil was comparable to 0.5 and 1uM doxorubicin, a
      commonly used clinical drug for OS treatment. CONCLUSION: These results indicate
      that krill oil may be used in combination with standard clinical practices to
      control primary tumour growth, and more importantly, metastasis.

PMID- 25563593
TI  - Hyaluronic Acid as a Protein Polymeric Carrier: An Overview and a Report on Human
      Growth Hormone.
AB  - Hyaluronic acid (HA) is a natural polysaccharide primarily present in the
      vitreous humor and in cartilages where it plays a key structural role in
      organizing the cartilage extracellular matrix. HA is used in a wide range of
      applications including treatment of arthritis (as a viscosupplementation agent
      for joints) and in a variety of cosmetic injectable products. Its safety profile
      is thus well established. Thanks to its high biocompatibility and targeting
      properties, HA has also been investigated for use as a carrier of anticancer
      drugs and, recently, also of proteins. Its role in the last case is a
      particularly challenging one as dedicated coupling chemistries are required to
      preserve the protein's conformation and activity. This study focuses on the state
      of the art on protein HAylation. New data from our laboratory on the local
      delivery of specific biologics to joints will also be outlined. 

PMID- 25563594
TI  - Monosomal karyotype in acute myeloid leukemia and the role of allogeneic
      hematopoietic cell transplantation.
AB  - Monosomal karyotype (MK) in acute myeloid leukemia (AML) is associated with an
      extremely poor outcome. The clinical significance of MK and the role of
      allogeneic hematopoietic cell transplantation (HCT) were evaluated in 749 Korean
      patients with newly diagnosed AML. MK was found in 9.3% of patients and was more
      frequent in patients with advanced age or secondary AML. Patients with MK had
      significantly lower blood leukocyte counts and bone marrow blast percentages, and
      they had lower complete remission (CR) rate (43%) and shorter median overall
      survival (OS) (6.5 months) and relapse-free survival (RFS) (10.0 months) than any
      other prognostic group. MK+ patients who received allogeneic HCT at the first CR
      had higher OS [hazard ratio (HR) 0.344, P = 0.018], RFS (HR 0.257, P = 0.006),
      and lower relapse probability (HR 0.264, P = 0.008) than those not receiving.
      This study's results confirmed poor outcomes for AML patients with MK and suggest
      that allogeneic HCT at the first CR may improve outcome.

PMID- 25563595
TI  - Quality of life in multiple myeloma: clinical validation of the Mexican-Spanish
      version of the QLQ-MY20 instrument.
AB  - Health-related quality of life (HRQL) has become an important outcome measurement
      in hematology. Our aim was to validate the quality of life questionnaire (QLQ)
      MY20 instrument in patients with multiple myeloma (MM) in Mexico. The Mexican
      Spanish versions of the QLQ-C30 and QLQ-MY20 instruments were applied to patients
      with MM at a cancer referral centre. Reliability and validity tests were
      performed. Test-retest was carried out in selected patients. Ninety-eight
      patients with MM were included in this study. Questionnaire compliance rates were
      high, and the instrument was well accepted; internal consistency tests
      demonstrated good convergent and divergent validity. Cronbach's alpha
      coefficients of seven of nine multi-item scales of the QLQ-C30 and of all three
      multi-item scales of the QLQ-MY20 instruments were >0.7 (range, 0.36-0.89). The
      scales of the QLQ-C30 and QLQ-MY20 instruments distinguished among clinically
      distinct groups of patients; 9 of 15 scales of the QLQ-C30 and all 4 scales of
      the QLQ-MY20 presented responsiveness after change over time. The Mexican-Spanish
      version of the QLQ-MY20 questionnaire is reliable and valid for the assessment of
      HRQL in patients with MM and can be used in clinical trials in the Mexican
      community. 

PMID- 25563596
TI  - A 5-year follow-up in deferasirox treatment: improvement of cardiac and hepatic
      iron overload and amelioration in cardiac function in thalassemia major patients.
AB  - Deferasirox (DFX) is an oral iron chelator with established efficacy and safety.
      We evaluated by T2* cardiovascular magnetic resonance (CMR) the efficacy of DFX
      in preventing and removing cardiac and liver iron load and cardiac volume
      changes, along 5 years in adult thalassemia major (TM) patients. Twenty-three TM
      patients (9 males/14 women, mean age 36 +/- 4 years) were included in this study.
      Repeated CMR was performed to assess myocardial and liver iron load (baseline t0,
      after 2.5 years t1, after 5 years t2). Myocardial T2* values changed
      progressively and increased significantly between t0 and t2 (t0: 27.15 +/- 9.58
      vs t2: 36.64 +/- 6.68, p = 0.0001). At baseline evaluation, a cardiac T2* value
      <20 ms was detected in six patients (26 %): they showed an improvement of cardiac
      T2* values between t0 and t1, with normal T2* levels reached in all patients at
      t2. In the overall population, a significant reduction of both end-diastolic and
      end-systolic left ventricular volumes (EDV, ESV) were detected between t0 and t2
      (EDV, t0: 132 +/- 31 ml vs t2: 124 +/- 22 ml, p = 0.033; ESV, t0: 48 +/- 14 ml vs
      t2: 41 +/- 10 ml, p = 0.0007). A significant reduction in liver iron
      concentration (LIC) was detected at t1 (5.36 +/- 3.58 mg/g dw at baseline vs 3.35
      +/- 2.68 mg/g dw at t1, p = 0.004). In patients with cardiac iron overload at
      baseline (n.6), mean cardiac T2* values doubled at t2, and mean LIC value is
      reduced of 29 %. After 5 years of treatment, DFX continually and significantly
      reduced myocardial and liver iron overload, and it prevented further iron
      deposition. 

PMID- 25563597
TI  - Refractory mixed autoimmune hemolysis, thrombocytopenia, and thrombosis: a
      diagnostic puzzle.

PMID- 25563598
TI  - Validation of an enhanced International Prognostic Index (NCCN-IPI) in an Asian
      cohort of patients with diffuse large B cell lymphoma.

PMID- 25563599
TI  - Histone methyltransferase SMYD3 regulates the expression of transcriptional
      factors during bovine oocyte maturation and early embryonic development.
AB  - Mammalian early embryonic development is controlled by a unique program of gene
      expression, and involves epigenetic reprogramming of histone modifications and
      DNA methylation. SET and MYND domain-containing protein 3 (SMYD3) is a histone H3
      lysine 4 methyltransferase that plays important roles in transcription
      regulation. The expression of SMYD3 has been studied in some cancer cell lines.
      However, its expression in oocytes and embryos has not previously been reported.
      Here, we detected the SMYD3 mRNA and found that it was expressed throughout
      bovine oocyte in vitro maturation and early embryonic development. Microinjection
      of SMYD3 siRNA at germinal vesicle stage decreased the transcription level of
      NANOG, and blocked the development of in vitro fertilization embryos at 4-8 cell
      stage. Conversely, Microinjection of SMYD3 siRNA at pronuclear stage did not
      affect early embryonic development. Our findings suggest that SMYD3 regulates the
      expression of NANOG, and plays an essential role in bovine early embryonic
      development. 

PMID- 25563600
TI  - Host-pathogen interactome analysis of Chikungunya virus envelope proteins E1 and
      E2.
AB  - The envelope proteins of Chikungunya virus (CHIKV) are known to play crucial
      roles in viral infection and spread. Although the role of envelope proteins in
      viral infection has been studied, the cellular interactors of these proteins are
      still elusive. In the present study, the ectodomains of CHIKV envelope proteins
      (E1 and E2) have been used for a high throughput yeast two-hybrid (Y2H) screening
      to identify the interacting host protein partners. Following a comparative
      analysis between the viral-host protein interaction data generated from Y2H and
      computational approach, five host proteins interacting with E1 and three host
      proteins interacting with E2 common to both datasets were identified. These
      associations were further verified independently by pull down and protein
      interaction ELISA. The identified interactions shed light on the possible
      cellular machinery that CHIKV might be employing during viral entry, trafficking,
      and evasion of immune system. 

PMID- 25563601
TI  - Blood or spores? A cautionary note on interpreting cellular debris on human
      skeletal remains.
AB  - The identification of red blood cells on both skeletal human remains and
      decomposed corpses is of remarkable importance in forensic sciences, irrespective
      of its diagnostic value; their presence is often perplexing and difficult to
      interpret especially when in the context of decomposition and taphonomical
      variables. Some clinical research has focused on the morphological changes of red
      blood cells over time by scanning electron microscopy (SEM), but no research has
      investigated whether botanical structures can be confused for red blood cells.
      Since some literature has recently presumed the detection of erythrocyte-like
      cells on skeletal remains (even ancient) as surely erythrocytes, and most have
      never taken into consideration the chance of an origin different from blood, such
      as botanical, the present study aims at verifying the possibility of confusion
      between erythrocytes and botanical cells by applying SEM analysis and at
      highlighting the pitfalls in this particular issue through a test submitted to
      pathologists and natural scientists asked to discriminate between red blood cells
      and different vegetal structures (60 images obtained by SEM analysis). The
      results showed that although there are diagnostic features useful in identifying
      red blood cells from botanical structures, some spores resulted very similar to
      decaying red blood cells, which calls for attention and great caution when
      studying decomposed human remains. 

PMID- 25563602
TI  - Revision of the letter to the editor by Abergel and Claverie.

PMID- 25563603
TI  - Identification of differentially expressed genes of brown trout (Salmo trutta)
      and rainbow trout (Oncorhynchus mykiss) in response to Tetracapsuloides
      bryosalmonae (Myxozoa).
AB  - Tetracapsuloides bryosalmonae Canning et al., 1999 (Myxozoa) is the causative
      agent of proliferative kidney disease in various species of salmonids in Europe
      and North America. We have shown previously that the development and distribution
      of the European strain of T. bryosalmonae differs in the kidney of brown trout
      (Salmo trutta) Linnaeus, 1758 and rainbow trout (Oncorhynchus mykiss) Walbaum,
      1792, and that intra-luminal sporogonic stages were found in brown trout but not
      in rainbow trout. We have now compared transcriptomes from kidneys of brown trout
      and rainbow trout infected with T. bryosalmonae using suppressive subtractive
      hybridization (SSH). The differentially expressed transcripts produced by SSH
      were cloned, transformed, and tested by colony PCR. Differential expression
      screening of PCR products was validated using dot blot, and positive clones
      having different signal intensities were sequenced. Differential screening and a
      subsequent NCBI-BLAST analysis of expressed sequence tags revealed nine clones
      expressed differently between both fish species. These differentially expressed
      genes were validated by quantitative real-time PCR of kidney samples from both
      fish species at different time points of infection. Expression of anti
      inflammatory (TSC22 domain family protein 3) and cell proliferation (Prothymin
      alpha) genes were upregulated significantly in brown trout but downregulated in
      rainbow trout. The expression of humoral immune response (immunoglobulin mu) and
      endocytic pathway (Ras-related protein Rab-11b) genes were significantly
      upregulated in rainbow trout but downregulated in brown trout. This study
      suggests that differential expression of host anti-inflammatory, humoral immune
      and endocytic pathway responses, cell proliferation, and cell growth processes do
      not inhibit the development of intra-luminal sporogonic stages of the European
      strain of T. bryosalmonae in brown trout but may suppress it in rainbow trout.

PMID- 25563604
TI  - Variations in the excretion patterns of helminth eggs in two sympatric mouse
      lemur species (Microcebus murinus and M. ravelobensis) in northwestern
      Madagascar.
AB  - Many factors can influence the parasite load of animal hosts, but integrative
      studies that simultaneously investigate several factors are still rare in many
      taxonomic groups. This study investigates the influence of host species, host
      population density, parasite transmission mode, sex, and two temporal (month,
      year) factors on gastrointestinal parasite prevalence and fecal egg counts of two
      endemic primate species from Madagascar, Microcebus ravelobensis and Microcebus
      murinus. A total of 646 fecal samples were available and analyzed from three dry
      seasons. Six different helminth egg morphotypes were found, and these were
      Subulura sp. (14.51 % prevalence), strongyle eggs (12.95 %), Ascaris sp. (7.94
      %), Lemuricola sp. (0.17 %), and two forms of tapeworms (Hymenolepis spp.) (1.73
      and 0.69 %). Coinfection with more than one egg type was observed in 21.22 % of
      the samples containing eggs. Multivariate analyses revealed that host species and
      sex did neither explain significant variation in the prevalence and fecal egg
      counts of parasites with direct life cycles (Ascaris sp., strongyle egg type,
      Lemuricola sp.) nor of arthropod-transmitted parasites (Subulura sp.). However,
      fecal egg counts of Subulura sp. differed significantly between study sites, and
      the prevalence of Subulura sp. and of parasites with direct life cycles was
      influenced by temporal parameters, mainly by differences between study years and
      partly between months. When comparing the findings with the yearly and seasonal
      rainfall patterns in the area, most results are in accordance with the hypothesis
      of an increased vulnerability of the host toward infection under some sort of
      environmental challenge.

PMID- 25563606
TI  - Redefinition of Nosema pyrausta (Perezia pyraustae Paillot 1927) basing upon
      ultrastructural and molecular phylogenetic studies.
AB  - Populations of European corn borer (Ostrinia nubilalis Hubner) from Krasnodar
      Territory (Southwestern Russia) become regularly infected with Nosema-like
      microsporidia. To identify the parasite, it was subjected to electron microscopy
      and small subunit ribosomal RNA (SSU rRNA) gene sequencing. The spore
      ultrastructure of the parasite was highly similar to Nosema bombycis from China
      and Nosema pyrausta from the USA. The nucleotide sequence of SSU rRNA gene was
      identical to a microsporidium isolated from O. nubilalis in southern France
      (GenBank accession no. HM566196) and closely related to Nosema bombycis (no.
      AY209011, 99.7 % sequence similarity) from Bombyx mori of Chinese origin and N.
      pyrausta (no. AY958071) from O. nubilalis of North American origin. As the
      molecular haplotype of SSU rRNA is fixed for the parasite infecting O. nubilalis
      across Europe and N. pyrausta was initially described in France as Perezia
      pyraustae (Paillot CR Acad Sci Paris 185: 673-675, 1927), we conclude that the
      parasite examined under the present study correspond to the type isolate of N.
      pyrausta. The microsporidium from O. nubilalis in North America (no. AY958071)
      corresponds therefore to a closely related, yet distinct haplotype.

PMID- 25563605
TI  - Mediterranean essential oils as effective weapons against the West Nile vector
      Culex pipiens and the Echinostoma intermediate host Physella acuta: what happens
      around? An acute toxicity survey on non-target mayflies.
AB  - Mosquitoes (Diptera: Culicidae) represent a threat for millions of people
      worldwide, since they act as vectors for important pathogens, including malaria,
      yellow fever, dengue and West Nile. Second to malaria as the world's most
      widespread parasitic disease, infection by trematodes is a devastating public
      health problem. In this study, we proposed two essential oils from plants
      cultivated in Mediterranean regions as effective chemicals against mosquitoes and
      freshwater snails vectors of Echinostoma trematodes. Chemical composition of
      essential oils from Achillea millefolium (Asteraceae) and Haplophyllum
      tuberculatum (Rutaceae) was investigated. Acute toxicity was evaluated against
      larvae of the West Nile vector Culex pipiens (Diptera: Culicidae) and the
      invasive freshwater snail Physella acuta (Mollusca: Physidae), an important
      intermediate host of many parasites, including Echinostoma revolutum
      (Echinostomidae). Acute toxicity of essential oils was assessed also on a non
      target aquatic organism, the mayfly Cloeon dipterum (Ephemeroptera: Baetidae).
      Achillea millefolium and H. tuberculatum essentials oils were mainly composed by
      oxygenated monoterpenes (59.3 and 71.0 % of the whole oil, respectively).
      Chrysanthenone and borneol were the two major constituents of Achillea
      millefolium essential oil (24.1 and 14.2 %, respectively). Major compounds of H.
      tuberculatum essential oil were cis-p-menth-2-en-1-ol and trans-p-menth-2-en-1-ol
      (22.9 and 16.1 %, respectively). In acute toxicity assays, C. pipiens LC50 was
      154.190 and 175.268 ppm for Achillea millefolium and H. tuberculatum,
      respectively. P. acuta LC50 was 112.911 and 73.695 ppm for Achillea millefolium
      and H. tuberculatum, respectively, while the same values were 198.116 and 280.265
      ppm for C. dipterum. Relative median potency analysis showed that both tested
      essential oils were more toxic to P. acuta over C. dipterum. This research adds
      knowledge on plant-borne chemicals toxic against invertebrates of medical
      importance, allowing us to propose the tested oils as effective candidates to
      develop newer and safer vector control tools.

PMID- 25563607
TI  - Digenean larvae--the cause and beneficiaries of the changes in host snails'
      thermal behavior.
AB  - Parasite-induced changes in host's thermal preferences not only can be
      interpreted as a physiological defense response of the host but also can
      represent a pathological manifestation of the parasite. Both may become
      established in host-parasite relationships if they are beneficial for at least
      one of the counterparts. This study investigates parasite-induced changes in the
      thermoregulatory behavior of first intermediate hosts of Digenea (i.e. Lymnaea
      stagnalis and Planorbarius corneus), infected with Notocotylidae or
      Echinostomatidae larvae. The investigated parasite species developed different
      transmission strategies outside the body of a snail, which may imply a different
      effect on the behavior of their hosts. Notocotylus attenuatus in L. stagnalis and
      Notocotylus ephemera in P. corneus produce symptoms of anapyrexia, prolonging the
      lifespan of their hosts. By contrast, Echinoparyphium aconiatum in L. stagnalis
      and Echinostoma spiniferum in P. corneus interfere with defensive
      thermoregulatory behavior of host snails, causing their accelerated death. The
      results of laboratory research indicate that thermal preferences of the snails
      infected with all investigated trematodes facilitate the transmission of the
      parasites in environment.

PMID- 25563608
TI  - Population dynamics of two diplectanid species (Monogenea) parasitising sparid
      hosts (Sparidae).
AB  - Economically important sparid fish species, gilthead (Sparus aurata) and white
      seabream (Diplodus sargus) (Sparidae) are frequently parasitised by diplectanid
      monogeneans, known to induce severe losses in farming conditions. We have
      analysed population dynamic of two diplectanid species, Lamellodiscus echeneis
      and Lamellodiscus ignoratus (Monogenea: Diplectanidae) collected from two bream
      species in the Beymelek Lagoon (southwest coast of Turkey), comparing it between
      different host variables (fish size, age and sex) in order to have insight in
      parasites' ecology, important for managing parasitosis in the intensive
      aquaculture system. In seabream (N = 127), L. echeneis prevalence was 46.5 %
      (exact 95 % confidence limits 38.90-54.14), mean abundance 5.64 (bootstrap 95 %
      confidence limits 4.20-7.65) and mean intensity 12.14 (bootstrap 95 % confidence
      limits 9.49-15.59). In white seabream (N = 102), L. ignoratus prevalence was 24.5
      % (exact 95 % confidence limits 16.53-34.03), mean abundance 1.73 (bootstrap 95 %
      confidence limits 0.98-3.21) and mean intensity 7.04 (bootstrap 95 % confidence
      limits 4.60-11.40). Parasites' parameters differed only between seasons in both
      hosts and between age categories in gilthead, but not in white seabream.

PMID- 25563609
TI  - The effect of weather variables on the flight activity of horseflies (Diptera:
      Tabanidae) in the continental climate of Hungary.
AB  - Although the tabanid species and populations occurring in eastern central Europe
      (Carpathian Basin) are thoroughly studied, there are only sporadic data about the
      influence of weather conditions on the abundance and activity of horseflies. To
      fill in this lack, in Hungary, we performed a 3-month summer survey of horsefly
      catches registering the weather parameters. Using common canopy traps and
      polarization liquid traps, we found the following: (i) rainfall, air temperature,
      and sunshine were the three most important factors influencing the trapping
      number of tabanids. (ii) The effect of relative air humidity H on tabanids was
      indirect through the air temperature T: H ~ 35 % (corresponding to T ~ 32 
      degrees C) was optimal for tabanid trapping, and tabanids were not captured for H
      >= 80 % (corresponding to T <= 18  degrees C). (iii) A fast decrease in the air
      pressure enhanced the trapping number of both water-seeking and host-seeking
      horseflies. (iv) Wind velocities larger than 10 km/h reduced drastically the
      number of trapped tabanids. Our data presented here may serve as a reference for
      further investigations of the effect of climate change on tabanids in Europe.

PMID- 25563610
TI  - Toxoplasma gondii nucleus coding apicoplast protein ACP synthesis and trafficking
      in delayed death.
AB  - This study aimed to explore Toxoplasma gondii nucleus coding apicoplast protein
      acyl carrier protein (ACP) synthesis and trafficking in delayed death. The
      recombinant T. gondii ACP was expressed by prokaryotic expression method, and
      anti-ACP polyclonal antibody was obtained from rabbit immune. T. gondii "delayed
      death" was induced by clindamycin (CLDM), and ACP transcription was determined by
      real-time PCR assay. The expression of ACP with transit type (t-ACP) and mature
      type (m-ACP) was determined by Western blotting with anti-ACP polyclonal
      antibody. The mutant-expressed ACP fused with green fluorescent protein (GFP) tag
      was constructed by pHX-ACP-GFP. The distribution of ACP in "delayed death" was
      observed by ACP-GFP fusion protein with a confocal microscope. T. gondii ACP
      transcription and t-ACP expression had no significant decrease in the early 4 h
      of "delayed death," but there has been a significant decrease in 6 h. The
      expression of m-ACP had a significant decrease in 4 h which occurred earlier than
      the t-ACP expression. The number of brightly dot green fluorescence in ACP-GFP
      mutant decreased with prolonged time. There was very little brightly dot green
      fluorescence in ACP-GFP mutant when treated with CLDM for 6 h. CLDM could
      suppress apicoplast proliferation and induce T. gondii "delayed death"; however,
      it could not directly suppress nucleus coding ACP transcription and expression.
      T. gondii lacking of apicoplast had a barrier of transit peptide cleavage and t
      ACP could not be transformed into m-ACP. The reason for the decrease in ACP
      expression could be due to excessive t-ACP synthesis in tachyzoites resulting in
      a negative feedback for the ACP coding gene transcription.

PMID- 25563611
TI  - Topsoil conditions correlate with the emergence rates of Culicoides chiopterus
      and Culicoides dewulfi (Diptera: Ceratopogonidae) from cowpats.
AB  - Culicoides chiopterus (Meigen), 1830 and Culicoides dewulfi Goetghebuer, 1936
      (Diptera: Ceratopogonidae) are considered to develop exclusively in dung, but do
      not necessarily show an equal distribution and abundance on livestock farms in
      Northern Europe. Recent modelling studies identified soil parameters to explain
      these differences. The present study addressed the question whether topsoil
      conditions underneath cowpats correlate with the number of emerging C. chiopterus
      and C. dewulfi. We recorded the emergence of biting midges from 24 cowpats over a
      period of 4 weeks and analysed samples from the topsoil. In agreement with
      species distribution models based on remote data, our results detected the
      correlation of soil moisture, organic matter and soil texture with the number of
      emerging C. chiopterus and C. dewulfi. With increasing soil moisture, the number
      of emerging adults increased for both species and the amount of organic matter
      was positively correlated with the number of emerging C. chiopterus. In contrast,
      soil textures showed conflicting results, i.e. a positive and negative
      relationship with the same variables. According to our results, soil underneath
      dung can explain the number of emerging Culicoides species. The knowledge of
      these effects might improve the interpretation of large-scaled distribution
      models for dung-breeding biting midges.

PMID- 25563612
TI  - Old ingredients for a new recipe? Neem cake, a low-cost botanical by-product in
      the fight against mosquito-borne diseases.
AB  - Mosquitoes (Diptera: Culicidae) represent an important threat to millions of
      people worldwide, since they act as vectors for important pathogens, such as
      malaria, yellow fever, dengue and West Nile. Control programmes mainly rely on
      chemical treatments against larvae, indoor residual spraying and insecticide
      treated bed nets. In recent years, huge efforts have been carried out to propose
      new eco-friendly alternatives, with a special focus on the evaluation of plant
      borne mosquitocidal compounds. Major examples are neem-based products
      (Azadirachta indica A. Juss, Meliaceae) that have been proven as really effective
      against a huge range of pests of medical and veterinary importance, including
      mosquitoes. Recent research highlighted that neem cake, a cheap by-product from
      neem oil extraction, is an important source of mosquitocidal metabolites. In this
      review, we examined (i) the latest achievements about neem cake metabolomics with
      special reference to nor-terpenoid and related content; (ii) the neem cake
      ovicidal, larvicidal and pupicidal toxicity against Aedes, Anopheles and Culex
      mosquito vectors; (iii) its non-target effects against vertebrates; and (iv) its
      oviposition deterrence effects on mosquito females. Overall, neem cake can be
      proposed as an eco-friendly and low-cost source of chemicals to build newer and
      safer control tools against mosquito vectors.

PMID- 25563613
TI  - Prevalence of Cryptosporidium infection in captive lesser panda (Ailurus fulgens)
      in China.
AB  - Cryptosporidium is a global epidemic parasite and one of the most important
      intestinal pathogens causing diarrhea in animals and humans. Despite extensive
      research on this parasite group, little is known about rates of Cryptosporidium
      infection in lesser pandas. In this study, we use molecular diagnostic tools to
      detect Cryptosporidium infections and identify Cryptosporidium species in the
      lesser panda. Using a PCR approach, we sequenced the 18S rRNA gene in fecal
      samples collected from 110 captive lesser pandas held throughout China
      (approximately one third of the captive population). We determined
      Cryptosporidium species via a BLAST comparison of our sequences against those of
      published Cryptosporidium sequences available in GenBank and subsequent
      phylogenetic analysis. We report that captive lesser pandas were infected with a
      single Cryptosporidium species, Cryptosporidium andersoni, at a prevalence of
      6.36 % (7/110). The present investigation revealed the existence of C. andersoni
      infection in captive lesser panda and suggested that proper control measures
      should be taken carefully to protect the welfare of zoo workers and visitors.

PMID- 25563614
TI  - Dissections of fresh skulls confirm low prevalence of Troglotrema acutum
      (Trematoda: Troglotrematidae) in German badgers (Meles meles).
AB  - We examined 131 European badgers Meles meles (Linnaeus, 1758) from 67 localities
      in central Germany for the presence of the cranial trematode Troglotrema acutum,
      as previous studies based on museum skulls might have underestimated the
      prevalence of the parasite in this host. We detected the flatworm in only three
      individuals that originated from the Rhoen Mountains (Thurigina and Bavaria).
      While the cranium of one host individual showed the lesions and the sponge-like
      widening of certain regions of the skullcap that are typical of a T. acutum
      infection, the skulls of the two remaining badgers did not show any deformations.
      The three badgers were infected by eight, 20, and 49 T. acutum individuals,
      respectively. Eggs of the trematode parasite were detected in the paranasal
      sinuses of two badgers. While badgers infected with T. acutum may not show any
      surface bone lesions, the results of the present study do not contradict the
      conclusion that the badger is only an accidental host of T. acutum.

PMID- 25563616
TI  - Tigecycline inhibits proliferation of Acanthamoeba castellanii.
AB  - Acanthamoeba is an opportunistic protozoan parasite responsible for different
      diseases in humans, such as granulomatous amoebic encephalitis and amoebic
      keratitis. Tigecycline, a third-generation tetracycline antibiotic, has potential
      activity to treat most of the antibiotic resistant bacterial infections. The
      effects of tigecycline in eukaryotic cells as well as parasites are less well
      studied. In the present study, we tested the effects of tigecycline on
      trophozoites of Acanthamoeba castellanii. The inhibitory effect of tigecycline on
      Acanthamoeba was determined by resazurin reduction and trypan blue exclusion
      assays. We found that tigecycline significantly inhibited the growth of
      Acanthamoeba (46.4 % inhibition at the concentration of 100 MUM) without
      affecting cell viability and induction of encystation, whereas other tetracycline
      groups of antibiotics such as tetracycline and doxycycline showed no inhibitory
      effects. Furthermore, tigecycline decreased cellular adenosine triphosphate (ATP)
      level by 26 % than the control and increased mitochondrial mass, suggesting
      mitochondrial dysfunction in tigecycline-treated cells. These findings suggest
      that mitochondrial dysfunction with decreased ATP production might play an
      important mechanism of tigecycline in suppression of Acanthamoeba proliferation.

PMID- 25563617
TI  - Factors affecting sporoplasm release in Kudoa septempunctata.
AB  - The myxosporean parasite Kudoa septempunctata has been isolated from cultured
      olive flounder (Paralichthys olivaceus) and was recently identified as a cause of
      food poisoning in humans. Since the sporoplasm plays an important role in causing
      diarrhea by invading intestinal cells, the specific factors affecting the release
      of sporoplasm from spores should be determined. Thus, we investigated the effect
      of digestive and serum enzymes, fetal bovine serum (FBS), temperature, and the
      role of glucose in cell culture media on the release of sporoplasm. Sporoplasm
      release was observed in the groups treated with FBS and media containing glucose.
      In addition, 1,10-phenanthroline inhibited the release of sporoplasm in the FBS
      medium. These results indicate that K. septempunctata uses glucose for releasing
      its sporoplasm and that zinc or metalloprotease is related to the release
      mechanism. The present study provides important information for the development
      of agents to prevent sporoplasm release and the consequent food poisoning caused
      by K. septempunctata.

PMID- 25563618
TI  - Third-stage nematode larvae of Contracaecum osculatum from Baltic cod (Gadus
      morhua) elicit eosinophilic granulomatous reactions when penetrating the stomach
      mucosa of pigs.
AB  - Third-stage larvae of the anisakid nematode Contracaecum osculatum were recovered
      from livers of Atlantic cod (Gadus morhua) caught in the Baltic Sea (June 2014)
      and used for experimental infection of two pigs (one male and one female). Each
      pig received 215 larvae by oral infection (feeding with minced cod liver
      containing live nematode larvae). Pigs were euthanized after 5 days, necropsied,
      and subjected to parasitological investigation. A total of 12 larvae were found
      penetrating the mucosa of the ventricle (7 in the female pig and 5 in the male
      pig) eliciting a granulomatous reaction at the penetration site. Four non
      attached larvae were found in the female pig stomach and one in the male pig.
      Petechial bleeding was observed at several locations in the ventricular mucosa
      where larvae were located. Histological examination of the stomach mucosa
      revealed a massive cellular infiltration (giant cells, lymphocytes, macrophages,
      granulocytes, and fibroblast like cells) around the penetrating larva.
      Mononuclear and polymorphonuclear cells containing eosinophilic granulae were
      particularly prominent in the granulomas. Reactions correspond to reactions in
      pigs following experimental infection with the human pathogenic anisakid larvae
      Anisakis sp. and Pseudoterranova sp. which suggests that C. osculatum might have
      a zoonotic potential as well.

PMID- 25563619
TI  - A proposal for the experimental detection of CSL induced random walk.
AB  - Continuous Spontaneous Localization (CSL) is one possible explanation for
      dynamically induced collapse of the wave-function during a quantum measurement.
      The collapse is mediated by a stochastic non-linear modification of the
      Schrodinger equation. A consequence of the CSL mechanism is an extremely tiny
      violation of energy-momentum conservation, which can, in principle, be detected
      in the laboratory via the random diffusion of a particle induced by the
      stochastic collapse mechanism. In a paper in 2003, Collett and Pearle
      investigated the translational CSL diffusion of a sphere, and the rotational CSL
      diffusion of a disc, and showed that this effect dominates over the ambient
      environmental noise at low temperatures and extremely low pressures (about ten
      thousandth of a pico-Torr). In the present paper, we revisit their analysis and
      argue that this stringent condition on pressure can be relaxed, and that the CSL
      effect can be seen at the pressure of about a pico-Torr. A similar analysis is
      provided for diffusion produced by gravity-induced decoherence, where the effect
      is typically much weaker than CSL. We also discuss the CSL induced random
      displacement of a quantum oscillator. Lastly, we propose possible experimental
      set-ups justifying that CSL diffusion is indeed measurable with the current
      technology. 

PMID- 25563621
TI  - What is a network meta-analysis and how can we use it to inform clinical
      practice?

PMID- 25563615
TI  - Genome mining offers a new starting point for parasitology research.
AB  - Parasites including helminthes, protozoa, and medical arthropod vectors are a
      major cause of global infectious diseases, affecting one-sixth of the world's
      population, which are responsible for enormous levels of morbidity and mortality
      important and remain impediments to economic development especially in tropical
      countries. Prevalent drug resistance, lack of highly effective and practical
      vaccines, as well as specific and sensitive diagnostic markers are proving to be
      challenging problems in parasitic disease control in most parts of the world. The
      impressive progress recently made in genome-wide analysis of parasites of medical
      importance, including trematodes of Clonorchis sinensis, Opisthorchis viverrini,
      Schistosoma haematobium, S. japonicum, and S. mansoni; nematodes of Brugia
      malayi, Loa loa, Necator americanus, Trichinella spiralis, and Trichuris suis;
      cestodes of Echinococcus granulosus, E. multilocularis, and Taenia solium;
      protozoa of Babesia bovis, B. microti, Cryptosporidium hominis, Eimeria
      falciformis, E. histolytica, Giardia intestinalis, Leishmania braziliensis, L.
      donovani, L. major, Plasmodium falciparum, P. vivax, Trichomonas vaginalis,
      Trypanosoma brucei and T. cruzi; and medical arthropod vectors of Aedes aegypti,
      Anopheles darlingi, A. sinensis, and Culex quinquefasciatus, have been
      systematically covered in this review for a comprehensive understanding of the
      genetic information contained in nuclear, mitochondrial, kinetoplast, plastid, or
      endosymbiotic bacterial genomes of parasites, further valuable insight into
      parasite-host interactions and development of promising novel drug and vaccine
      candidates and preferable diagnostic tools, thereby underpinning the prevention
      and control of parasitic diseases.

PMID- 25563622
TI  - Bioresorbable vascular scaffolds in patients with acute coronary syndromes: the
      POLAR ACS study.
AB  - INTRODUCTION: The results of the ABSORB trial showed the efficacy and safety of
      bioresorbable vascular scaffolds (BVS) and their unique advantage, namely, the
      restoration of vasomotion after full biodegradation. OBJECTIVES: The aim of the
      registry was to evaluate procedural issues, angiographic results, and clinical
      outcomes of patients with acute coronary syndrome (ACS) treated with BVS
      implantation. PATIENTS AND METHODS: The study included 100 patients. Cohort 1
      comprised 46 patients with unstable angina; cohort 2, 38 patients with non-ST
      segment elevation myocardial infarction; and cohort 3, 16 patients with ST
      segment elevation myocardial infarction. RESULTS: Predilation was performed in
      93% of the patients. The final Thrombolysis In Myocardial Infarction (TIMI) 3
      flow was achieved in 99% of the patients. In all patients, BVS was successfully
      implanted. In 81% of the patients, postdilation was performed with a balloon
      catheter with the same diameter as BVS; in 11%, with a balloon catheter with a
      diameter of 0.25 mm larger than BVS; and in 7%, with a balloon catheter with a
      diameter of 0.5 mm larger than BVS. We observed no no-reflow phenomenon, 1 distal
      embolization, and 2 slow-flow phenomena. Two major adverse cardiac events were
      reported, namely, periprocedural myocardial infarction in 2 patients. During 1
      year follow-up, we observed only 1 additional myocardial infarction caused by
      stent thrombosis as well as 1 target lesion revascularization. CONCLUSIONS: In
      our study, BVS in patients with ACS showed to be a safe and effective procedure. 

PMID- 25563623
TI  - Aortic stenosis: new pathophysiological mechanisms and their therapeutic
      implications.
AB  - Aortic stenosis (AS) represents the most common type of acquired valvular heart
      disease. Its incidence increases with age; therefore, from 3% to 9% of adults
      over 75 years of age develop AS. The pathophysiological mechanisms and role of
      biomarkers in the prediction of AS have been extensively studied. Progression of
      AS is characterized by a number of abnormalities in calcification regulation,
      inflammation/adipokine dysregulation, prothrombic state, and altered von
      Willebrand factor function. The current understanding of the mechanisms of AS
      involves a complex role of the multiple cell types, in particular myofibroblasts
      and macrophages. The introduction of transcatheter aortic valve implantation
      provides invaluable opportunities for periprocedural and long-term monitoring of
      the changes in the biomarker profile. Effective pharmacological treatment,
      especially in the early stage of AS, is largely unknown. The current review
      discusses not only the pathophysiology of AS but also attempts at pharmacological
      treatment. 

PMID- 25563624
TI  - Echocardiographic and histopathological diagnosis of left ventricular
      noncompaction.

PMID- 25563625
TI  - Optical coherence tomography of inoperable chronic thromboembolic pulmonary
      hypertension treated with refined balloon pulmonary angioplasty.

PMID- 25563626
TI  - Failure of noninvasive ventilation during hypercapnic exacerbation of chronic
      obstructive pulmonary disease: the role of chronic kidney diseases.

PMID- 25563627
TI  - Failure of noninvasive ventilation during hypercapnic exacerbation of chronic
      obstructive pulmonary disease: the role of chronic kidney diseases. Authors'
      reply.

PMID- 25563628
TI  - [Not Available].

PMID- 25563629
TI  - "Getting the Left Right": The Experience of Hemispatial Neglect After Stroke.
AB  - We used a phenomenological approach to gain insight into the experiences of self,
      other, and world in patients with hemispatial neglect within the first month
      following stroke. Comprehensive descriptions of circumstances were conjoined with
      open-ended interviews of 12 participants. The neglect experience was captured in
      the overarching theme, "getting the left right," which encompasses the two
      subthemes of (a) surreal awareness of the left and (b) emergence of a different
      world. Patients had unclear perceptions of their own body and surroundings, their
      attention was brittle, and they encountered bewildering reactions from other
      people. They simultaneously pursued the ineffable neglected space and searched
      for coherence. The vulnerability, loss, and conflicting perceptions that patients
      with neglect face should be acknowledged and alleviation sought. Facilitating
      methods should provide additional opportunities for patients to communicate their
      experiences. We underscore the importance of readjusting the current approaches
      of neglect and emphasizing meaningfulness in professional guidance. 

PMID- 25563630
TI  - Trauma systems in Kenya: a qualitative analysis at the district level.
AB  - Injury is a leading cause of death and disability in low- and middle-income
      countries. Kenya has a particularly high burden of injuries, accounting for 88.4
      deaths per 100,000 population. Despite recent attempts to prioritize injury
      prevention in Kenya, trauma care systems have not been assessed. We assessed
      perceptions of formal and informal district-level trauma systems through 25
      qualitative semi-structured interviews and 16 focus group discussions with
      Ministry of Health officials, district hospital administrators, health care
      providers, police, and community members. We used the principles of theoretical
      analysis to identify common themes of prehospital and hospital trauma care. We
      found prehospital care relied primarily on "good Samaritans" and police. We
      described hospital care in terms of human resources, infrastructure, and
      definitive care. The interviewers repeatedly emphasized the lack of hospital
      infrastructure. We showed the need to develop prehospital care systems and
      strengthen hospital trauma care services. 

PMID- 25563632
TI  - Long-term results of ethanol sclerotherapy with or without adjunctive surgery for
      head and neck arteriovenous malformations.
AB  - INTRODUCTION: Ethanol sclerotherapy has shown favorable short-term efficacy in
      managing head and neck arteriovenous malformation (AVM) which is well known for
      high recurrence rate after treatment. The purpose of this study was to report
      immediate treatment results and long-term follow-up results of ethanol
      sclerotherapy in patients with head and neck AVMs. METHODS: We performed a
      retrospective review of 45 patients with head and neck AVMs treated between April
      1997 and December 2013 by using ethanol sclerotherapy with or without adjunctive
      surgery. The degree of AVM eradication was analyzed, and complications per
      treatment session were recorded. Long-term treatment effectiveness was assessed
      with clinical and imaging follow-up. RESULTS: In total, 132 sclerotherapies were
      performed in the 45 patients, with a total angiographic eradication rate of 17.8%
      (n = 8). Partial resolution was achieved in 34 patients, and three patients
      showed no response. Mean follow-up period was 56.6 months (range, 13-144 months).
      The long-term recurrence rate was 11.1% (5/45), and all recurrences occurred more
      than 3 years after the treatment with interval disease-controlled period. The
      major complication rate was 3.8% (5/132), and 34 minor complications (25.8%)
      occurred. CONCLUSIONS: Ethanol sclerotherapy is effective for achieving long-term
      durable cure of head and neck AVMs. In patients with non-curable disease, it is
      also effective for symptom palliation and long-term disease control. However,
      given recurrence after interval disease-controlled period, long-term follow-up
      should be required to detect recurrence in patients with any residual lesion
      after treatment.

PMID- 25563631
TI  - Tonsillar pulsatility before and after surgical decompression for children with
      Chiari malformation type 1: an application for true fast imaging with steady
      state precession.
AB  - INTRODUCTION: We hypothesize that surgical decompression for Chiari malformation
      type 1 (CM-1) is associated with statistically significant decrease in tonsillar
      pulsatility and that the degree of pulsatility can be reliably assessed
      regardless of the experience level of the reader. METHODS: An Institutional
      Review Board (IRB)-approved Health Insurance Portability and Accountability Act
      (HIPAA)-compliant retrospective study was performed on 22 children with CM-1 (8
      males; mean age 11.4 years) who had cardiac-gated true-FISP sequence and phase
      contrast cerebrospinal fluid (CSF) flow imaging as parts of routine magnetic
      resonance (MR) imaging before and after surgical decompression. The surgical
      technique (decompression with or without duraplasty) was recorded for each
      patient. Three independent radiologists with different experience levels assessed
      tonsillar pulsatility qualitatively and quantitatively and assessed peritonsillar
      CSF flow qualitatively. Results were analyzed. To evaluate reliability, Fleiss
      kappa for multiple raters on categorical variables and intra-class correlation
      for agreement in pulsatility ratings were calculated. RESULTS: After surgical
      decompression, the degree of tonsillar pulsatility appreciably decreased,
      confirmed by t test, both qualitatively (p values <0.001, <0.001, and 0.045 for
      three readers) and quantitatively (amount of decrease/p value for three readers
      0.7 mm/<0.001, 0.7 mm/<0.001, and 0.5 mm/0.022). There was a better agreement
      among the readers in quantitative assessment of tonsillar pulsatility (kappa
      0.753-0.834), compared to qualitative assessment of pulsatility (kappa 0.472
      0.496) and qualitative assessment of flow (kappa 0.056 to 0.203). Posterior fossa
      decompression with duraplasty led to a larger decrease in tonsillar pulsatility,
      compared to posterior fossa decompression alone. CONCLUSION: Tonsillar
      pulsatility in CM-1 is significantly reduced after surgical decompression.
      Quantitative assessment of tonsillar pulsatility was more reliable across readers
      than qualitative assessments of tonsillar pulsatility or CSF flow.

PMID- 25563634
TI  - Shikimic acid, a base compound for the formulation of swine/avian flu drug:
      statistical optimization, fed-batch and scale up studies along with its
      application as an antibacterial agent.
AB  - The sudden outbreak of swine flu has increased the global demand of shikimic acid
      which is an industrially interesting compound, as it is used as a key starting
      material for the synthesis of a neuraminidase inhibitor Tamiflu((r)), for the
      treatment of antiviral infections such as swine flu. Statistical optimization and
      evaluation of medium components for the production of shikimic acid by
      Citrobacter freundii is addressed in the present investigation. Plackett-Burman
      design was applied for the screening of the most significant variables affecting
      shikimic acid production, where glucose, asparagine, KH2PO4, CaCO3 and agitation
      rate were the most significant factors. Response surface methodology was also
      employed to study the interaction among the most significant variables through
      which shikimic acid production increased to 12.76 g/L. Further, fed-batch studies
      resulted in the production of 22.32 g/L of shikimic acid. The scalability of the
      process was also confirmed by running 14 L bioreactor (7.5 L production medium)
      where 20.12 g/L of shikimic acid was produced. In addition the antibacterial
      activity of the shikimic acid produced was analysed against four Gram positive
      and four Gram negative bacteria and it was found to have a greater inhibition
      effect against the Gram negative bacteria.

PMID- 25563635
TI  - Exploring the dynamics of bacterial community composition in soil: the pan
      bacteriome approach.
AB  - We performed a longitudinal study (repeated observations of the same sample over
      time) to investigate both the composition and structure of temporal changes of
      bacterial community composition in soil mesocosms, subjected to three different
      treatments (water and 5 or 25 mg kg(-1) of dried soil Cd(2+)). By analogy with
      the pan genome concept, we identified a core bacteriome and an accessory
      bacteriome. Resident taxa were assigned to the core bacteriome, while occasional
      taxa were assigned to the accessory bacteriome. Core and accessory bacteriome
      represented roughly 35 and 50 % of the taxa detected, respectively, and were
      characterized by different taxonomic signatures from phylum to genus level while
      15 % of the taxa were found to be unique to a particular sample. In particular,
      the core bacteriome was characterized by higher abundance of members of
      Planctomycetes, Actinobacteria, Verrucomicrobia and Acidobacteria, while the
      accessory bacteriome included more members of Firmicutes, Clamydiae and
      Proteobacteria, suggesting potentially different responses to environmental
      changes of members from these phyla. We conclude that the pan-bacteriome model
      may be a useful approach to gain insight for modeling bacterial community
      structure and inferring different abilities of bacteria taxa. 

PMID- 25563633
TI  - Agonist Medications for the Treatment of Cocaine Use Disorder.

PMID- 25563637
TI  - Composition and predicted functional ecology of mussel-associated bacteria in
      Indonesian marine lakes.
AB  - In the present study, we sampled bacterial communities associated with mussels
      inhabiting two distinct coastal marine ecosystems in Kalimantan, Indonesia,
      namely, marine lakes and coastal mangroves. We used 16S rRNA gene pyrosequencing
      and predicted metagenomic analysis to compare microbial composition and function.
      Marine lakes are small landlocked bodies of seawater isolated to varying degrees
      from the open sea environment. They contain numerous endemic taxa and represent
      natural laboratories of speciation. Our primary goals were to (1) use BLAST
      search to identify closely related organisms to dominant bacterial OTUs in our
      mussel dataset and (2) to compare bacterial communities and enrichment in the
      predicted bacterial metagenome among lakes. Our sequencing effort yielded 3553
      OTUs belonging to 44 phyla, 99 classes and 121 orders. Mussels in the largest
      marine lake (Kakaban) and the coastal mangrove habitat were dominated by bacteria
      belonging to the phylum Proteobacteria whereas smaller lakes, located on the
      island of Maratua, were dominated by bacteria belonging to the phyla Firmicutes
      and Tenericutes. The single most abundant OTU overall was assigned to the genus
      Mycoplasma. There were several significant differences among locations with
      respect to metabolic pathways. These included enrichment of xenobiotic
      biodegradation pathways in the largest marine lake and coastal mangrove. These
      locations were also the most enriched with respect to nitrogen metabolism. The
      presence of genes related to isoquinoline alkaloids, polyketides, hydrolases,
      mono and dioxygenases in the predicted analysis of functional pathways is an
      indication that the bacterial communities of Brachidontes mussels may be
      potentially important sources of new marine medicines and enzymes of industrial
      interest. Future work should focus on measuring how mussel microbial communities
      influence nutrient dynamics within the marine lake environment and isolating
      microbes with potential biotechnological applications. 

PMID- 25563638
TI  - General practice web-based decision aid improves MMR vaccination uptake.

PMID- 25563636
TI  - Ornithinibacillus composti sp. nov., isolated from sludge compost and emended
      description of the genus Ornithinibacillus.
AB  - A Gram-stain positive, aerobic, motile, endospore-forming and rod-shaped
      bacterium, designated GSS05(T), was isolated from a sludge compost sample and was
      characterized by means of a polyphasic taxonomic approach. Growth was observed to
      occur with 0-3 % (w/v) NaCl (optimum 1 %), at pH 5.5-10 (optimum pH 7.5) and at
      15-50  degrees C (optimum 37  degrees C). According to the results of a
      phylogenetic analysis, strain GSS05(T) was found to belong to the genus
      Ornithinibacillus and to be related most closely to the type strains of
      Ornithinibacillus halotolerans and Ornithinibacillus contaminans (96.5 and 95.1 %
      16S rRNA gene sequence similarity, respectively). The peptidoglycan amino acid
      type was determined to be A4beta. The major respiratory quinone was identified as
      menaquinone-7 (MK-7). The polar lipid profile of strain GSS05(T) was found to
      contain a predominance of diphosphatidylglycerol, moderate amounts of
      phosphatidylglycerol and minor amounts of two unknown phospholipids and two
      unknown lipids. The G+C content of genomic DNA was determined to be 42.1 mol%.
      The dominant cellular fatty acids were identified as iso-C15:0 and anteiso-C15:0.
      The phenotypic, chemotaxonomic, phylogenetic and genotypic data indicated that
      strain GSS05(T) represents a novel species of the genus Ornithinibacillus, for
      which the name Ornithinibacillus composti sp. nov. is proposed. The type strain
      is GSS05(T) (=CCTCC AB 2013261(T) = KCTC 33192(T)). 

PMID- 25563639
TI  - A single nurse-led educational session may facilitate transition from paediatric
      to adult healthcare for adolescents with heart disease.

PMID- 25563640
TI  - Plaque components in symptomatic moderately stenosed carotid arteries related to
      cerebral infarcts: the plaque at RISK study.
AB  - BACKGROUND AND PURPOSE: Carotid plaque composition is a major determinant of
      cerebrovascular events. In the present analysis, we evaluated the relationship
      between intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (TRFC) in
      moderately stenosed carotid arteries and cerebral infarcts on MRI in the
      ipsilateral hemisphere. METHODS: A total of 101 patients with a symptomatic 30%
      to 69% carotid artery stenosis underwent MRI of the carotid arteries and the
      brain, within a median time of 45 days from onset of symptoms. The presence of
      ipsilateral infarcts in patients with and without IPH and TRFC was evaluated.
      RESULTS: IPH was seen in 40 of 101 plaques. TRFC was seen in 49 of 86 plaques
      (postcontrast series were not obtained in 15 patients). In total, 51 infarcts in
      the flow territory of the symptomatic carotid artery were found in 47 patients.
      Twenty nine of these infarcts, found in 24 patients, were cortical infarcts. No
      significant relationship was found between IPH or TRFC and the presence of
      ipsilateral infarcts. CONCLUSIONS: MRI detected IPH and TRFC are not related to
      the presence of old and recent cortical and subcortical infarcts ipsilateral to a
      symptomatic carotid artery stenosis of 30% to 69%. CLINICAL TRIAL REGISTRATION
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT01208025.

PMID- 25563641
TI  - Triage, treatment, and transfer: evidence-based clinical practice recommendations
      and models of nursing care for the first 72 hours of admission to hospital for
      acute stroke.

PMID- 25563643
TI  - Fibroblast growth factor 23 and risk of incident stroke in community-living
      adults.
AB  - BACKGROUND AND PURPOSE: Fibroblast growth factor 23 (FGF23) is a hormone that
      regulates phosphorus and vitamin D metabolism. Elevated FGF23 concentrations are
      associated with excess risk of cardiovascular disease. Associations of FGF23 with
      stroke outcomes are less clear. METHODS: Using a case-cohort study design, we
      examined the association of baseline plasma FGF23 concentrations with incident
      stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS)
      study, a cohort of black and white adults aged >=45 years. FGF23 was measured in
      615 participants who developed incident stroke (cases) and in 936 participants
      randomly selected from the REGARDS cohort (comparison subcohort). RESULTS: In
      multivariable-adjusted models, higher calcium and phosphorus concentrations,
      lower estimated glomerular filtration rate and higher urine albumin excretion
      were independently associated with higher FGF23. There was no statistically
      significant association of FGF23 with risk of all-cause stroke in Cox models
      adjusted for demographic factors and established stroke risk factors (hazard
      ratio comparing fourth with first quartile 1.19; 95% confidence interval, 0.78
      1.82). In prespecified models stratified by stroke subtypes, there was a graded
      association of FGF23 with risk of cardioembolic stroke in fully adjusted models
      (quartile 1, reference; quartile 2 hazard ratio, 1.48; 95% confidence interval,
      0.63-3.47; quartile 3 hazard ratio, 1.99; 95% confidence interval, 0.89-4.44;
      quartile 4 hazard ratio, 2.52; 95% confidence interval, 1.08-5.91). There were no
      statistically significant associations of FGF23 with other ischemic stroke
      subtypes or with hemorrhagic strokes. CONCLUSIONS: Higher FGF23 concentrations
      were associated with higher risk of cardioembolic but not with other stroke
      subtypes in community-dwelling adults. Additional studies should delineate
      reasons for these findings.

PMID- 25563642
TI  - Vascular imaging abnormalities and cognition: mediation by cortical volume in
      nondemented individuals: atherosclerosis risk in communities-neurocognitive
      study.
AB  - BACKGROUND AND PURPOSE: The relationships between cerebrovascular lesions visible
      on imaging and cognition are complex. We explored the possibility that the
      cerebral cortical volume mediated these relationships. METHODS: Total of 1906
      nondemented participants (59% women; 25% African-American; mean age, 76.6 years)
      in the Atherosclerosis Risk in Communities (ARIC) study underwent cognitive
      assessments, risk factor assessments, and quantitative MRI for white matter
      hyperintensities (WMH) and infarcts. The Freesurfer imaging analysis pipeline was
      used to determine regional cerebral volumes. We examined the associations of
      cognitive domain outcomes with cerebral volumes (hippocampus and separate groups
      of posterior and frontal cortical regions of interest) and cerebrovascular
      imaging features (presence of large or small cortical/subcortical infarcts and
      WMH volume). We performed mediation pathway analyses to assess the hypothesis
      that hippocampal and cortical volumes mediated the associations between
      cerebrovascular imaging features and cognition. RESULTS: In unmediated analyses,
      WMH and infarcts were both associated with worse psychomotor speed/executive
      function. In mediation analyses, WMH and infarct associations on psychomotor
      speed/executive function were significantly attenuated, but not abolished, by the
      inclusion of the posterior cortical regions of interest volume in the models, and
      the infarcts on psychomotor speed/executive function association were attenuated,
      but not abolished, by inclusion of the frontal cortical regions of interest
      volume. CONCLUSIONS: Both WMH and infarcts were associated with cortical volume,
      and both lesions were also associated with cognitive performance, implying shared
      pathophysiological mechanisms. Although cross-sectional, our findings suggest
      that WMH and infarcts could be proxies for clinically covert processes that
      directly damage cortical regions. Microinfarcts are 1 candidate for such a
      clinically covert process.

PMID- 25563645
TI  - What is the use of hypothermia for neuroprotection after out-of-hospital cardiac
      arrest?

PMID- 25563644
TI  - Job strain and the risk of stroke: an individual-participant data meta-analysis.
AB  - BACKGROUND AND PURPOSE: Psychosocial stress at work has been proposed to be a
      risk factor for cardiovascular disease. However, its role as a risk factor for
      stroke is uncertain. METHODS: We conducted an individual-participant-data meta
      analysis of 196 380 males and females from 14 European cohort studies to
      investigate the association between job strain, a measure of work-related stress,
      and incident stroke. RESULTS: In 1.8 million person-years at risk (mean follow-up
      9.2 years), 2023 first-time stroke events were recorded. The age- and sex
      adjusted hazard ratio for job strain relative to no job strain was 1.24 (95%
      confidence interval, 1.05;1.47) for ischemic stroke, 1.01 (95% confidence
      interval, 0.75;1.36) for hemorrhagic stroke, and 1.09 (95% confidence interval,
      0.94;1.26) for overall stroke. The association with ischemic stroke was robust to
      further adjustment for socioeconomic status. CONCLUSION: Job strain may be
      associated with an increased risk of ischemic stroke, but further research is
      needed to determine whether interventions targeting job strain would reduce
      stroke risk beyond existing preventive strategies.

PMID- 25563647
TI  - Ethanol and normobaric oxygen: novel approach in modulating pyruvate
      dehydrogenase complex after severe transient and permanent ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke induces metabolic disarray. A central
      regulatory site, pyruvate dehydrogeanse complex (PDHC) sits at the cross-roads of
      2 fundamental metabolic pathways: aerobic and anaerobic. In this study, we
      combined ethanol (EtOH) and normobaric oxygen (NBO) to develop a novel treatment
      to modulate PDHC and its regulatory proteins, namely pyruvate dehydrogenase
      phosphatase and pyruvate dehydrogenase kinase, leading to improved metabolism and
      reduced oxidative damage. METHODS: Sprague-Dawley rats were subjected to
      transient (2, 3, or 4 hours) middle cerebral artery occlusion followed by 3- or
      24-hour reperfusion, or permanent (28 hours) middle cerebral artery occlusion
      without reperfusion. At 2 hours after the onset of ischemia, rats received either
      an intraperitoneal injection of saline, 1 dose of EtOH (1.5 g/kg) for 2- and 3
      hour middle cerebral artery occlusion, 2 doses of EtOH (1.5 g/kg followed by 1.0
      g/kg in 2 hours) in 4 hours or permanent middle cerebral artery occlusion, and
      EtOH+95% NBO (at 2 hours after the onset of ischemia for 6 hours) in permanent
      stroke. Infarct volumes and neurological deficits were examined. Oxidative
      metabolism and stress were determined by measuring ADP/ATP ratio and reactive
      oxygen species levels. Protein levels of PDHC, pyruvate dehydrogenase kinase, and
      pyruvate dehydrogenase phosphatase were assessed. RESULTS: EtOH induced dose
      dependent neuroprotection in transient ischemia. Compared to EtOH or NBO alone,
      NBO+EtOH produced the best outcomes in permanent ischemia. These therapies
      improved brain oxidative metabolism by decreasing ADP/ATP ratios and reactive
      oxygen species levels, in association with significantly raised levels of PDHC
      and pyruvate dehydrogenase phosphatase, as well as decreased pyruvate
      dehydrogenase kinase. CONCLUSIONS: Both EtOH and EtOH+NBO treatments conferred
      neuroprotection in severe stroke by affecting brain metabolism. The treatment may
      modulate the damaging cascade of metabolic events by bringing the PDHC activity
      back to normal metabolic levels.

PMID- 25563646
TI  - Diffusional kurtosis and diffusion tensor imaging reveal different time-sensitive
      stroke-induced microstructural changes.
AB  - BACKGROUND AND PURPOSE: Diffusion MRI is a promising, clinically feasible imaging
      technique commonly used to describe white matter changes after stroke. We
      investigated the sensitivity of diffusion MRI to detect microstructural
      alterations in gray matter after sensorimotor cortex stroke in adult male rats.
      METHODS: The mean diffusivity (MD) and mean kurtosis of perilesional motor cortex
      were compared with measures in the contralesional forelimb area of sensorimotor
      cortex at 2 hours, 24 hours, 72 hours, or 25 days after surgery. MD and mean
      kurtosis were correlated to the surface densities of glia, dendrites, and axons.
      RESULTS: Perilesional mean kurtosis was increased at 72 hours and 25 days after
      stroke, whereas MD was no longer different from contralesional sensorimotor
      cortex at 24 hours after stroke. There was a significant increase in the density
      of glial processes at 72 hours after stroke in perilesional motor cortex, which
      correlated with perilesional MD. CONCLUSIONS: These data support that mean
      kurtosis and MD provide different but complimentary information on acute and
      chronic changes in perilesional cortex. Glia infiltration is associated with
      pseudonormalization of MD in the perilesional motor cortex at 72 hours after
      lesion; however, this association is absent 25 days after lesion. These data
      suggest that there are likely several different, time-specific microstructural
      changes underlying these 2 complimentary diffusion measures.

PMID- 25563648
TI  - Comparison and evaluation of dietary quality between older and younger Mexican
      American women.
AB  - OBJECTIVE: To compare and evaluate the dietary quality of young and older
      sedentary Mexican-American women. Understanding key dietary concerns, while
      considering developmental transition periods and cultural relevance, can provide
      insight for developing appropriate nutrition interventions. DESIGN: Cross
      sectional dietary data were collected using unannounced 24 h diet recalls to
      assess nutrient intake adequacy (Estimated Average Requirement cut-point method)
      and dietary quality (Healthy Eating Index (HEI) 2010). SETTING: Mujeres en Accion
      and Madres para la Salud, two community-based physical activity interventions.
      SUBJECTS: Participants were 139 young (28 (sd 6) years) and 124 older (55 (sd 7)
      years) overweight/obese sedentary Mexican-American women (BMI=25.0-35.0 kg/m2) of
      low socio-economic status. RESULTS: Older women consumed less Ca, Fe, folate,
      empty calories and energy from carbohydrate, but more fruit, vegetables, greens
      and beans, and fibre than younger women (all P<0.05). Over 60 % of all
      participants had an intake below recommendations for fibre, Ca, vitamin E,
      vitamin C and folate. Both groups had low total HEI-2010 scores (62 for older and
      63 for younger women; NS), with 57 % of older and 48 % of younger women
      classified as having a poor diet. CONCLUSIONS: Despite differences in nutrient
      requirements according to developmental transition periods (childbearing v.
      perimenopausal), overall, older and younger Mexican-American women generally had
      low-quality diets and may benefit from dietary quality improvement.

PMID- 25563649
TI  - Deception in simplicity: hereditary phospholamban mutations in dilated
      cardiomyopathy.
AB  - The sarcoplasmic reticulum (SR) calcium pump (SERCA) and its regulator
      phospholamban are required for cardiovascular function. Phospholamban alters the
      apparent calcium affinity of SERCA in a process that is modulated by
      phosphorylation via the beta-adrenergic pathway. This regulatory axis allows for
      the dynamic control of SR calcium stores and cardiac contractility. Herein we
      focus on hereditary mutants of phospholamban that are associated with heart
      failure, such as Arg(9)-Cys, Arg(9)-Leu, Arg(9)-His, and Arg(14)-deletion. Each
      mutant has a distinct effect on PLN function and SR calcium homeostasis. Arg(9)
      Cys and Arg(9)-Leu do not inhibit SERCA, Arg(14)-deletion is a partial inhibitor,
      and Arg(9)-His is comparable to wild-type. While the mutants have distinct
      functional effects on SERCA, they have in common that they cannot be
      phosphorylated by protein kinase A (PKA). Arg(9) and Arg(14) are required for PKA
      recognition and phosphorylation of PLN. Thus, mutations at these positions
      eliminate beta-adrenergic control and dynamic cardiac contractility. Hydrophobic
      mutations of Arg(9) cause more complex changes in function, including loss of PLN
      function and dominant negative interaction with SERCA in heterozygous
      individuals. In addition, aberrant interaction with PKA may prevent
      phosphorylation of wild-type PLN and sequester PKA from other local subcellular
      targets. Herein we consider what is known about each mutant and how the
      synergistic changes in SR calcium homeostasis lead to impaired cardiac
      contractility and dilated cardiomyopathy. 

PMID- 25563651
TI  - Copper-promoted aerial oxidation of benzothiadiazines: access to benzothiadiazine
      S-oxide heterocycles.
AB  - Cu(II)-promoted aerial oxidation of a series of benzothiadiazines () under
      ambient conditions affords the first structurally characterised examples of
      thiadiazine S-oxides (). The isolation of the homoleptic Cu(II) 3-(2'
      pyridyl)benzothiadiazide-S-oxide complex provides insight into the reaction
      mechanism. 

PMID- 25563652
TI  - Plectoneme tip bubbles: coupled denaturation and writhing in supercoiled DNA.
AB  - We predict a novel conformational regime for DNA, where denaturation bubbles form
      at the tips of plectonemes, and study its properties using coarse-grained
      simulations. For negative supercoiling, this regime lies between bubble-dominated
      and plectoneme-dominated phases, and explains the broad transition between the
      two observed in experiment. Tip bubbles cause localisation of plectonemes within
      thermodynamically weaker AT-rich sequences, and can greatly suppress plectoneme
      diffusion by a pinning mechanism. They occur for supercoiling densities and
      forces that are typically encountered for DNA in vivo, and may be exploited for
      biological control of genomic processes. 

PMID- 25563650
TI  - Synergistic effect of angiotensin II on vascular endothelial growth factor-A
      mediated differentiation of bone marrow-derived mesenchymal stem cells into
      endothelial cells.
AB  - INTRODUCTION: Increased levels of angiotensin II (Ang II) and activity of Ang II
      receptor type 1 (AT1R) elicit detrimental effects in cardiovascular disease.
      However, the role of Ang II receptor type 2 (AT2R) remains poorly defined.
      Mesenchymal stem cells (MSCs) replenish and repair endothelial cells in the
      cardiovascular system. Herein, we investigated a novel role of angiotensin
      signaling in enhancing vascular endothelial growth factor (VEGF)-A-mediated
      differentiation of MSCs into endothelial cells (ECs). METHODS: Bone marrow was
      aspirated from the femurs of Yucatan microswine. MSCs were extracted via ficoll
      density centrifugation technique and were strongly immunopositive for MSC
      markers, CD44, CD90, and CD105, but negative for hematopoietic markers, CD14 and
      CD45. Subsequently, naive MSCs were differentiated for 10 days in varying
      concentrations and combinations of VEGF-A, Ang II, and AT1R or AT2R antagonists.
      Markers specific to ECs were determined by FACS analysis. RESULTS: AT1R and AT2R
      expression and cellular localization was demonstrated in MSCs stimulated with
      VEGF-A and Ang II via quantitative RT-PCR and immunofluorescence, respectively.
      Differentiation of naive MSCs in media containing Ang II (2 ng/ml) plus low-dose
      VEGF-A (2 ng/ml) produced a significantly higher percentage of cells that were
      positive for expression of EC markers (for example, platelet endothelial cell
      adhesion molecule, vascular endothelial Cadherin and von Willebrand factor)
      compared to VEGF-A alone. Ang II alone failed to induce EC marker expression.
      MSCs differentiated with the combination of Ang II and VEGF-A were capable of
      forming capillary tubes using an in vitro angiogenesis assay. Induction of EC
      marker expression was greatly attenuated by co-treatment of Ang II/VEGF-A with
      the AT2R antagonist PD123319, but not the AT1R antagonist telmisartan.
      CONCLUSIONS: We report the presence of functional AT2R receptor on porcine bone
      marrow-derived MSCs, where it positively regulates EC differentiation. These
      findings have significant implications toward therapeutic approaches based on
      activation of AT2R, which could be a means to stimulate regeneration of damaged
      endothelium and prevent vascular thrombosis.

PMID- 25563653
TI  - cis-Semihydrogenation of alkynes with amine borane complexes catalyzed by gold
      nanoparticles under mild conditions.
AB  - Supported gold nanoparticles catalyze the semihydrogenation of alkynes to alkenes
      with ammonia borane or amine borane complexes in excellent yields and under mild
      conditions. Internal alkynes provide cis-alkenes, making this protocol an
      attractive alternative of the classical Lindlar's hydrogenation. 

PMID- 25563654
TI  - Peptide synthesis beyond DMF: THF and ACN as excellent and friendlier
      alternatives.
AB  - To date, DMF has been considered as the only solvent suitable for peptide
      synthesis. Here we demonstrate the capacity of THF and ACN, which are friendlier
      solvents than DMF, to yield the product in higher purity than DMF. Using various
      peptide models, both THF and ACN reduced racemization in solution-phase and solid
      phase synthesis when compared with DMF. Moreover, the use of ACN and THF in the
      solid-phase peptide synthesis of hindered peptides, such as Aib-enkephalin
      pentapeptide and Aib-ACP decapeptide, in combination with a complete polyethylene
      glycol resin (ChemMatrix), gave a better coupling efficiency than DMF. 

PMID- 25563655
TI  - The effects of an HPV education program by gender among Korean university
      students.
AB  - PURPOSE: This study compared the effects of an HPV education program by gender
      among Korean university students in terms of their knowledge of HPV, intention to
      prevent HPV, awareness of sexual rights, and perception of gender equality.
      METHODS: A quasi-experimental pre-post design was employed. 31 male and 28 female
      university students participated in eight sessions of an HPV prevention program
      for four weeks and in a self-administrative survey. RESULTS: At pre-test, the
      perception of gender equality and some of the intentions to prevent HPV,
      including the intention to make regular use of condoms, reduce the number of
      sexual partners, abstain from sex until marriage, and stop smoking or stay non
      smoker, were lower among men than women. When these differences by gender at pre
      test were taken into account using ANCOVA, education outcome measures at post
      test did not differ by gender. After completing the HPV prevention program, both
      male and female students presented a significant increase in terms of HPV
      knowledge, awareness of sexual rights, and perception of gender equality. Among
      the intentions to prevent HPV, only male intention to recommend the Pap test to
      their partner and female intention to regularly seek the Pap test and pelvic
      examinations were significantly increased after the program. CONCLUSION: The HPV
      program was effective for both genders eliminating gender differences in
      attitudes and prevention intentions of HPV. However, the intentions to prevent
      HPV did not increase significantly, and future research is warranted to better
      understand students' perceived obstacles for practicing HPV prevention methods.

PMID- 25563656
TI  - Teaching styles used in Malawian BSN programmes: a survey of nurse educator
      preferences.
AB  - AIM: This paper describes the teaching styles employed by Malawian nurse
      educators in the four year Bachelor of Science in Nursing (BSN) programme,
      according to Grasha's (1996) five teaching styles. BACKGROUND: An analysis of the
      educational processes of undergraduate nurses in Malawi followed anecdotal
      reports from stakeholders on the low levels of nurses' performance in the
      workplace. It was postulated that, in most instances, nursing students are
      exposed to traditional teaching approaches that do not equip them with skills for
      a demanding and ever-changing healthcare system. METHODS: A survey was conducted
      as part of a two-phased, sequential, explanatory mixed methods study. The target
      population comprised fifty nurse educators (N=50) who were invited to participate
      in the survey. Data were collected using Grasha's Teaching Styles Inventory
      (Version 3.0). A total of 44 inventories (n=44) were returned amounting to a
      response rate of 88%. Survey results were analysed using the Statistical Package
      for the Social Sciences (SPSS), version 16.0. Descriptive statistics were used to
      analyse the data. RESULTS: The Expert and Delegator teaching styles were
      moderately preferred (x 4.02; SD 1.06) by the majority of nurse educators
      (70.45%; n=31 and 86.36%; n=38 respectively). The Facilitator teaching style was
      the least preferred (x 3.7; SD 1.43) by 66.90% of educators (n=29), who also
      reported weak facilitative skills in the sub-scales. Similarly, educators
      reported a low preference for the Personal Model teaching style (x 3.6; SD 1.17).
      CONCLUSION: Teacher-centred styles tend to dominate the teaching activities of
      Malawian nurse educators in the BSN programme. Facilitative pedagogical
      approaches must be encouraged coupled with appropriate staff development that
      enables educators to facilitate learning with confidence, competence and self
      efficacy.

PMID- 25563657
TI  - Experiential learning in nursing consultation education via clinical simulation
      with actors: action research.
AB  - This was an action research study conducted during an undergraduate nursing
      course. The objective was to propose and implement experiential learning for
      nursing consultation education using clinical simulation with actors. The 4 steps
      of action research were followed: planning, action, observation and reflection.
      Three nursing undergraduate students participated in the study. Data were
      collected in May and July 2013 via participant comments and interviews and were
      analyzed in accordance with the operative proposal for qualitative data analysis.
      Planning included constructing and validating the clinical guides, selecting and
      training the actors, organizing and preparing the scenario and the issuing
      invitations to the participants. The action was carried out according to Kolb's
      (1984) 4 stages of learning cycles: Concrete Experience, Reflective Observation,
      Abstract Conceptualization and Active Experimentation. Clinical simulation
      involves different subjects' participation in all stages, and action research is
      a method that enables the clinical stimulation to be implemented. It must be
      guided by clear learning objectives and by a critical pedagogy that encourages
      critical thinking in students. Using actors and a real scenario facilitated
      psychological fidelity, and debriefing was the key moment of the reflective
      process that facilitated the integral training of students through experiential
      learning. 

PMID- 25563658
TI  - Regional alcohol consumption and alcohol-related mortality in Great Britain:
      novel insights using retail sales data.
AB  - BACKGROUND: Regional differences in population levels of alcohol-related harm
      exist across Great Britain, but these are not entirely consistent with
      differences in population levels of alcohol consumption. This incongruence may be
      due to the use of self-report surveys to estimate consumption. Survey data are
      subject to various biases and typically produce consumption estimates much lower
      than those based on objective alcohol sales data. However, sales data have never
      been used to estimate regional consumption within Great Britain (GB). This
      ecological study uses alcohol retail sales data to provide novel insights into
      regional alcohol consumption in GB, and to explore the relationship between
      alcohol consumption and alcohol-related mortality. METHODS: Alcohol sales
      estimates derived from electronic sales, delivery records and retail outlet
      sampling were obtained. The volume of pure alcohol sold was used to estimate per
      adult consumption, by market sector and drink type, across eleven GB regions in
      2010-11. Alcohol-related mortality rates were calculated for the same regions and
      a cross-sectional correlation analysis between consumption and mortality was
      performed. RESULTS: Per adult consumption in northern England was above the GB
      average and characterised by high beer sales. A high level of consumption in
      South West England was driven by on-trade sales of cider and spirits and off
      trade wine sales. Scottish regions had substantially higher spirits sales than
      elsewhere in GB, particularly through the off-trade. London had the lowest per
      adult consumption, attributable to lower off-trade sales across most drink types.
      Alcohol-related mortality was generally higher in regions with higher per adult
      consumption. The relationship was weakened by the South West and Central Scotland
      regions, which had the highest consumption levels, but discordantly low and very
      high alcohol-related mortality rates, respectively. CONCLUSIONS: This study
      provides support for the ecological relationship between alcohol-related
      mortality and alcohol consumption. The synthesis of knowledge from a combination
      of sales, survey and mortality data, as well as primary research studies, is key
      to ensuring that regional alcohol consumption, and its relationship with alcohol
      related harms, is better understood.

PMID- 25563659
TI  - Copper-catalyzed oxidative coupling of acids with alkanes involving
      dehydrogenation: facile access to allylic esters and alkylalkenes.
AB  - We here describe a new copper-catalyzed oxidative coupling of acids with alkanes
      for the selective synthesis of allylic esters and alkylalkenes. This method
      achieves multiple dehydrogenation and esterification, representing a new
      unactivated C(sp(3))-H oxidative esterification of acids with common alkanes. 

PMID- 25563661
TI  - Can appropriate use criteria lead to appropriate care?

PMID- 25563660
TI  - Can physicians identify inappropriate nuclear stress tests? An examination of
      inter-rater reliability for the 2009 appropriate use criteria for radionuclide
      imaging.
AB  - BACKGROUND: We sought to determine inter-rater reliability of the 2009
      Appropriate Use Criteria for radionuclide imaging and whether physicians at
      various levels of training can effectively identify nuclear stress tests with
      inappropriate indications. METHODS AND RESULTS: Four hundred patients were
      randomly selected from a consecutive cohort of patients undergoing nuclear stress
      testing at an academic medical center. Raters with different levels of training
      (including cardiology attending physicians, cardiology fellows, internal medicine
      hospitalists, and internal medicine interns) classified individual nuclear stress
      tests using the 2009 Appropriate Use Criteria. Consensus classification by 2
      cardiologists was considered the operational gold standard, and sensitivity and
      specificity of individual raters for identifying inappropriate tests were
      calculated. Inter-rater reliability of the Appropriate Use Criteria was assessed
      using Cohen kappa statistics for pairs of different raters. The mean age of
      patients was 61.5 years; 214 (54%) were female. The cardiologists rated 256 (64%)
      of 400 nuclear stress tests as appropriate, 68 (18%) as uncertain, 55 (14%) as
      inappropriate; 21 (5%) tests were unable to be classified. Inter-rater
      reliability for noncardiologist raters was modest (unweighted Cohen kappa, 0.51,
      95% confidence interval, 0.45-0.55). Sensitivity of individual raters for
      identifying inappropriate tests ranged from 47% to 82%, while specificity ranged
      from 85% to 97%. CONCLUSIONS: Inter-rater reliability for the 2009 Appropriate
      Use Criteria for radionuclide imaging is modest, and there is considerable
      variation in the ability of raters at different levels of training to identify
      inappropriate tests.

PMID- 25563662
TI  - Medical device postapproval safety monitoring: where does the United States
      stand?

PMID- 25563663
TI  - Reduction in peripheral regulatory T cell population in childhood ocular type
      myasthenia gravis.
AB  - OBJECTIVE: Myasthenia gravis (MG) is a T-cell dependent and antibody mediated
      autoimmune disease. Recent studies of adult patients and animal models have shown
      that regulatory T cells (Tregs) play an important role in the pathogenesis of MG,
      but little is known about MG in children. This study evaluated the role of
      peripheral blood Tregs in childhood ocular MG and assessed if Tregs could be an
      index for estimating immunological status. PATIENTS AND METHODS: Clinical data
      and peripheral lymphocytes were obtained from 13 children with serum AChR
      antibody-positive ocular type MG and 18 age-matched controls. Committed cells
      from MG patients were divided into two clinical stages: active (n=12) and
      remission (n=11). Tregs and Th17 cells were analyzed by flow cytometric analysis
      based on CD4(+)CD25(+) intracellular Foxp3(+) and CD4(+) intracellular IL-17A(+)
      fractions, respectively. RESULTS: The percentage of Tregs among peripheral blood
      CD4(+) T cells in active stage, remission stage, and control groups was 3.3+/
      1.3%, 4.8+/-1.7%, and 5.0+/-0.6%, respectively. The Treg population was
      significantly lower in the active stage than in the remission stage and controls.
      Furthermore, Treg percentage was significantly lower during relapse of myasthenia
      symptoms. We witnessed no remarkable associations between the percentage of Tregs
      and immune suppressant dosages. CONCLUSIONS: A significant reduction in the
      peripheral Treg population is considered to contribute to the pathophysiology of
      ocular type childhood MG and may be a marker of immunological state in these
      patients.

PMID- 25563664
TI  - From graphene oxide to pristine graphene: revealing the inner workings of the
      full structural restoration.
AB  - High temperature annealing is the only method known to date that allows the
      complete repair of a defective lattice of graphenes derived from graphite oxide,
      but most of the relevant aspects of such restoration processes are poorly
      understood. Here, we investigate both experimentally (scanning probe microscopy)
      and theoretically (molecular dynamics simulations) the thermal evolution of
      individual graphene oxide sheets, which is rationalized on the basis of the
      generation and the dynamics of atomic vacancies in the carbon lattice. For
      unreduced and mildly reduced graphene oxide sheets, the amount of generated
      vacancies was so large that they disintegrated at 1773-2073 K. By contrast,
      highly reduced sheets survived annealing and their structure could be completely
      restored at 2073 K. For the latter, a minor atomic-sized defect with six-fold
      symmetry was observed and ascribed to a stable cluster of nitrogen dopants. The
      thermal behavior of the sheets was significantly altered when they were supported
      on a vacancy-decorated graphite substrate, as well as for the overlapped/stacked
      sheets. In these cases, a net transfer of carbon atoms between neighboring sheets
      via atomic vacancies takes place, affording an additional healing process. Direct
      evidence of sheet coalescence with the step edge of the graphite substrate was
      also gathered from experiments and theory. 

PMID- 25563665
TI  - Asymmetric Kita spirolactonisation catalysed by anti-dimethanoanthracene-based
      iodoarenes.
AB  - Enantiopure C2-symmetric iodoarenes based on the rigid all-carbon anti
      dimethanoanthracene framework are shown to catalyse the asymmetric oxidative Kita
      spirolactonisation of propanoic acid-tethered 1-naphthols with significant levels
      of asymmetric induction of up to 67% ee. 

PMID- 25563667
TI  - Vanadyl species-catalyzed complementary beta-oxidative carbonylation of styrene
      derivatives with aldehydes.
AB  - A series of oxometallic species and metal acetylacetonates (acac) was examined as
      catalysts for oxidative carbonylation of styrene with benzaldehyde using t
      butylhydroperoxide as the co-oxidant in warm acetonitrile. Among them, VO((acac)2
      and vanadyl(IV) chloride were found to be the only catalyst class to achieve
      cross-coupling processes by judiciously tuning the ligand electronic attributes,
      leading to beta-hydroxylation- and beta-peroxidation-carbonylation of styrene,
      respectively, in a complementary manner. Mechanistic studies indicated that
      vanadyl-associated acyl radicals generated by t-butoxy radical-assisted,
      homolytic cleavage of the aldehyde C-H bond were involved in tandem processes
      with an exclusive syn diastereoselectivity in the case of beta-methylstyrene.

PMID- 25563666
TI  - Emotional and behavioral problems in late-identified Indonesian patients with
      disorders of sex development.
AB  - OBJECTIVE: The aim of this study is to investigate emotional and behavioral
      problems among Indonesian patients with disorders of sex development (DSD) who
      recently came under clinical management. As diagnostic procedures and treatment
      had been delayed, patients progressively developed ambiguous bodies, difficult to
      conceal from outsiders. METHOD: We compared 118 Indonesian patients with DSD aged
      6-41 years (60 children, 24 adolescents, 34 adults) and 118 healthy control
      subjects matched for age, gender, and residential settings. We used the Child
      Behavioral Checklist (CBCL), Youth Self-Report (YSR), and Adult Self-Report (ASR)
      to examine differences between patient and control groups as well as differences
      within patients groups. RESULTS: On the CBCL, parents of young children with DSD
      reported significantly more emotional and behavioral problems than parents of
      matched control. Parents of daughters with CAH reported that their daughters
      withdrew themselves from social interactions. On the ASR, adults with DSD
      reported significantly more internalizing problems than controls, particularly
      anxiety and depression. No other differences in emotional functioning were found
      across different diagnostic groups. CONCLUSIONS: Indonesian patients with DSD who
      were untreated for most of their lives suffered more emotional and behavioral
      problems than matched controls. Differences and similarities between our findings
      and observations in patients from Western countries will be discussed.

PMID- 25563668
TI  - Corrigendum: Effect of aminoguanidine on sciatic functional index, oxidative
      stress, and rate of apoptosis in an experimental rat model of ischemia
      reperfusion injury.

PMID- 25563669
TI  - How connected are people with schizophrenia? Cell phone, computer, email, and
      social media use.
AB  - Technologies such as Internet based social media network (SMN) websites are
      becoming an important part of many adult lives; however, less is known about
      their use in patients with schizophrenia. We need to determine (1) how
      "connected" are patients with schizophrenia?, (2) do these technologies interfere
      with the patient's illness?, and (3) do patients envision these technologies
      being involved in their treatment? We recruited 80 inpatients and outpatients age
      18-70 with schizophrenia to complete a brief survey on the prevalence and
      frequency of cell phone, text messaging, computer, email, and SMN use, and
      associated attitudes. 56% of subjects use text messaging, 48% have an email
      account, and 27% of subjects use SMN sites daily, with Facebook being the most
      popular. Many current users agreed that these technologies help them
      interact/socialize more, expressed interest in receiving text messages from their
      doctors, and disagreed that these technologies make symptoms worse. These
      preliminary findings should be investigated in larger samples, but suggest that
      these technologies afford a unique opportunity to engage and improve treatment
      for some patients with schizophrenia. 

PMID- 25563670
TI  - Bcl-2 associated with severity of manic symptoms in bipolar patients in a manic
      phase.
AB  - B cell lymphoma protein-2 (Bcl-2) may contribute to the pathophysiology of
      bipolar disorder, and may be involved in the therapeutic action of anti-manic
      drugs. The aim of this study was to investigate serum levels of Bcl-2 in bipolar
      patients in a manic phase, and evaluate the Bcl-2 changes after treatment. We
      consecutively enrolled 23 bipolar inpatients in a manic phase and 40 healthy
      subjects; 20 bipolar patients were followed up with treatment. Serum Bcl-2 levels
      were measured with assay kits. All 20 patients were evaluated by examining the
      correlation between Bcl-2 levels and Young Mania Rating Scale (YMRS) scores,
      using Spearman's correlation coefficients. The serum Bcl-2 levels in bipolar
      patients in a manic phase were higher than in healthy subjects, but without a
      significant difference. The YMRS scores were significantly negatively associated
      with serum Bcl-2 levels (p=0.042). Bcl-2 levels of the 20 bipolar patients were
      measured at the end of treatment. Using the Wilcoxon Signed Rank test, we found
      no significant difference in the Bcl-2 levels of bipolar patients after
      treatment. Our results suggest that Bcl-2 levels might be an indicator of
      severity of manic symptoms in bipolar patients in a manic phase. 

PMID- 25563671
TI  - Influence of social cognition on daily functioning in schizophrenia: study of
      incremental validity and mediational effects.
AB  - While the role of impaired neurocognition in accounting for functional outcome in
      schizophrenia is generally established, the influence of social cognition on this
      relationship is far from clear. This study aims to explore in depth the nature of
      the relationship between neurocognition, social cognition and daily functioning
      in people with schizophrenia. Twenty-one individuals diagnosed with schizophrenia
      and 15 controls completed the assessment of symptom severity, neuropsychological
      status, social cognition (Theory of Mind and affect processing) and other
      functional measures. A statistical mediation model based on hierarchical
      regression analyses was used to establish the mediation path with significant
      variables. Social cognition played a mediating role between neurocognition and
      functioning, accounting for significant trends in incremental variance in
      specific functional indexes (interpersonal behavior and employment/occupation).
      Consequently, this study adds to the evidence underlining the importance of
      targeting not only social cognitive or neurocognitive functions but to combine
      both interventions to reveal the best daily functioning results in schizophrenia
      patients. 

PMID- 25563674
TI  - A short-term operating room surgery scheduling problem integrating multiple
      nurses roster constraints.
AB  - OBJECTIVES: Operating room (OR) surgery scheduling determines the individual
      surgery's operation start time and assigns the required resources to each surgery
      over a schedule period, considering several constraints related to a complete
      surgery flow and the multiple resources involved. This task plays a decisive role
      in providing timely treatments for the patients while balancing hospital resource
      utilization. The originality of the present study is to integrate the surgery
      scheduling problem with real-life nurse roster constraints such as their role,
      specialty, qualification and availability. This article proposes a mathematical
      model and an ant colony optimization (ACO) approach to efficiently solve such
      surgery scheduling problems. METHOD: A modified ACO algorithm with a two-level
      ant graph model is developed to solve such combinatorial optimization problems
      because of its computational complexity. The outer ant graph represents
      surgeries, while the inner graph is a dynamic resource graph. Three types of
      pheromones, i.e. sequence-related, surgery-related, and resource-related
      pheromone, fitting for a two-level model are defined. The iteration-best and
      feasible update strategy and local pheromone update rules are adopted to
      emphasize the information related to the good solution in makespan, and the
      balanced utilization of resources as well. The performance of the proposed ACO
      algorithm is then evaluated using the test cases from (1) the published
      literature data with complete nurse roster constraints, and 2) the real data
      collected from a hospital in China. RESULTS: The scheduling results using the
      proposed ACO approach are compared with the test case from both the literature
      and the real life hospital scheduling. Comparison results with the literature
      shows that the proposed ACO approach has (1) an 1.5-h reduction in end time; (2)
      a reduction in variation of resources' working time, i.e. 25% for ORs, 50% for
      nurses in shift 1 and 86% for nurses in shift 2; (3) an 0.25h reduction in
      individual maximum overtime (OT); and (4) an 42% reduction in the total OT of
      nurses. Comparison results with the real 10-workday hospital scheduling further
      show the advantage of the ACO in several measurements. Instead of assigning all
      surgeries by a surgeon to only one OR and the same nurses by traditional manual
      approach in hospital, ACO realizes a more balanced surgery arrangement by
      assigning the surgeries to different ORs and nurses. It eventually leads to
      shortening the end time within the confidential interval of [7.4%, 24.6%] with
      95% confidence level. CONCLUSION: The ACO approach proposed in this paper
      efficiently solves the surgery scheduling problem with daily nurse roster while
      providing a shortened end time and relatively balanced resource allocations. It
      also supports the advantage of integrating the surgery scheduling with the nurse
      scheduling and the efficiency of systematic optimization considering a complete
      three-stage surgery flow and resources involved.

PMID- 25563675
TI  - Effect of Positive Airway Pressure Therapy on Body Mass Index in Obese Patients
      With Obstructive Sleep Apnea Syndrome: A Prospective Study.
AB  - Because obesity is a common cause of obstructive sleep apnea syndrome (OSAS),
      weight loss can be an effective treatment. OSAS also may cause weight gain in
      some patients. Effective treatment of sleep apnea may facilitate weight loss in
      obese patients. We hypothesize that positive airway pressure (PAP) therapy is
      associated with weight loss in obese patients with OSAS. This was a single-center
      observational prospective cohort study. Forty-five patients were diagnosed with
      OSAS after polysomnographic analysis in sleep laboratory and underwent continuous
      positive airway pressure titration. Patients were followed for 3 months in terms
      of change in body mass index (BMI) and compliance with PAP therapy. Of the 45
      patients recruited, 3 patients were eliminated because of miss recruitment. Nine
      patients had incomplete data, and the rest (n = 33) were included for analysis.
      The mean age was 54.9 +/- 16.9 years (mean +/- SD), 93.9% were male, and 90.9%
      were whites. Mean apnea-hypopnea index was 36.3 +/- 28.17 events per hour. Mean
      BMI before treatment was 34.7 +/- 3.9 kg/m. Fifteen patients (45.5%) were
      compliant with therapy of OSAS with PAP. There was no difference in age, gender,
      neck circumference, BMI, and apnea-hypopnea index of patients compliant to
      therapy when compared with those who were not. There was a significant decrease
      in BMI in patients compliant with PAP therapy compared with noncompliant patients
      (-1.2 +/- 0.7 vs. 0.3 +/- 0.9 kg/m, P <= 0.001). PAP therapy may cause
      significant loss of weight within 3 months in obese patients with OSAS. Further
      study is needed to elucidate the physiological basis of this change. 

PMID- 25563677
TI  - The Effects of Plyometric Type Neuromuscular Training on Postural Control
      Performance of Male Team Basketball Players.
AB  - Anterior cruciate ligament injuries are common in basketball athletes; common
      preventive programs for decreasing these injures may be enhancing postural
      control (PC) or balance with plyometric training. This study investigated the
      efficiency of plyometric training program within basketball practice to improve
      PC performance in young basketball players. Sixteen players were recruited and
      assigned either to a plyometric + basketball training group (PT) or basketball
      training group (BT). All players trained twice per week, but the PT + BT followed
      a 6-week plyometric program implemented within basketball practice, whereas the
      BT followed regular practice. The star excursion balance test (SEBT) at 8
      directions (anterior, A; anteromedial, AM; anterolateral, AL; medial, M; lateral,
      L; posterior, P; posteromedial, PM; and posterolateral, PL) was measured before
      and after the 6-week period. The PT group induced significant improvement (p <=
      0.05) and small to moderate effect size in the SEBT (A = 0.95, AM = 0.62, AL =
      0.61, M = 0.36, L = 0.47, P = 0.27, PM = 0.25, PL = 0.24). No significant
      improvements were found in the BT group. Also, there were significant differences
      between groups in all directions except PM and PL. An integrated plyometric
      program within the regular basketball practice can lead to significant
      improvements in SEBT and consequently PC. It can be recommended that strength and
      conditioning professionals use PT to enhance the athletes' joint awareness and PC
      to reduce possible future injuries in the lower extremity.

PMID- 25563676
TI  - Determining Best Practices to Reduce Occupational Health Risks in Firefighters.
AB  - The physical demands of firefighting are extensive, and firefighters face
      increased risk of cardiovascular and metabolic disease, musculoskeletal injury,
      and cancer. To reduce these risks, a tailored wellness initiative program (FIT
      Firefighter) was developed and executed. Implementation of FIT Firefighter,
      consisting of assessment, educational, instructional, and personal coaching and
      training elements regarding nutrition, health, fitness, wellness, and strength
      and conditioning, revealed enhanced healthy behavior change including increased
      motivation and marked improvements in blood pressure, resting heart rate, aerobic
      fitness, body mass index, waist circumference, percent body fat, back
      flexibility, and biceps strength among participating firefighters.

PMID- 25563673
TI  - Application of quantitative trait locus mapping and transcriptomics to studies of
      the senescence-accelerated phenotype in rats.
AB  - BACKGROUND: Etiology of complex disorders, such as cataract and neurodegenerative
      diseases including age-related macular degeneration (AMD), remains poorly
      understood due to the paucity of animal models, fully replicating the human
      disease. Previously, two quantitative trait loci (QTLs) associated with early
      cataract, AMD-like retinopathy, and some behavioral aberrations in senescence
      accelerated OXYS rats were uncovered on chromosome 1 in a cross between OXYS and
      WAG rats. To confirm the findings, we generated interval-specific congenic
      strains, WAG/OXYS-1.1 and WAG/OXYS-1.2, carrying OXYS-derived loci of chromosome
      1 in the WAG strain. Both congenic strains displayed early cataract and
      retinopathy but differed clinically from OXYS rats. Here we applied a high
      throughput RNA sequencing (RNA-Seq) strategy to facilitate nomination of the
      candidate genes and functional pathways that may be responsible for these
      differences and can contribute to the development of the senescence-accelerated
      phenotype of OXYS rats. RESULTS: First, the size and map position of QTL-derived
      congenic segments were determined by comparative analysis of coding single
      nucleotide polymorphisms (SNPs), which were identified for OXYS, WAG, and
      congenic retinal RNAs after sequencing. The transferred locus was not what we
      expected in WAG/OXYS-1.1 rats. In rat retina, 15442 genes were expressed.
      Coherent sets of differentially expressed genes were identified when we compared
      RNA-Seq retinal profiles of 20-day-old WAG/OXYS-1.1, WAG/OXYS-1.2, and OXYS rats.
      The genes most different in the average expression level between the congenic
      strains included those generally associated with the Wnt, integrin, and TGF-beta
      signaling pathways, widely involved in neurodegenerative processes. Several
      candidate genes (including Arhgap33, Cebpg, Gtf3c1, Snurf, Tnfaip3, Yme1l1, Cbs,
      Car9 and Fn1) were found to be either polymorphic in the congenic loci or
      differentially expressed between the strains. These genes may contribute to the
      development of cataract and retinopathy. CONCLUSIONS: This study is the first RNA
      Seq analysis of the rat retinal transcriptome generated with 40 mln sequencing
      read depth. The integration of QTL and transcriptomic analyses in our study forms
      the basis of future research into the relationship between the candidate genes
      within the congenic regions and specific changes in the retinal transcriptome as
      possible causal mechanisms that underlie age-associated disorders.

PMID- 25563678
TI  - Thrombin generation potential and whole-blood DNA methylation.

PMID- 25563680
TI  - Spectroscopic, biological, and molecular modeling studies on the interactions of
      [Fe(III)-meloxicam] with G-quadruplex DNA and investigation of its release from
      bovine serum albumin (BSA) nanoparticles.
AB  - The guanine-rich sequence, specifically in DNA, telomeric DNA, is a potential
      target of anticancer drugs. In this work, a mononuclear Fe(III) complex
      containing two meloxicam ligands was synthesized as a G-quadruplex stabilizer.
      The interaction between the Fe(III) complex and G-quadruplex with sequence of 5'
      G3(T2AG3)3-3' (HTG21) was investigated using spectroscopic methods, molecular
      modeling, and polymerase chain reaction (PCR) assays. The spectroscopic methods
      of UV-vis, fluorescence, and circular dichroism showed that the metal complex can
      effectively induce and stabilize G-quadruplex structure in the G-rich 21-mer
      sequence. Also, the binding constant between the Fe(III) complex and G-quadruplex
      was measured by these methods and it was found to be 4.53(+/-0.30) * 10(5) M(
      1)). The PCR stop assay indicated that the Fe(III) complex inhibits DNA
      amplification. The cell viability assay showed that the complex has significant
      antitumor activities against Hela cells. According to the UV-vis results, the
      interaction of the Fe(III) complex with duplex DNA is an order of magnitude lower
      than G-quadruplex. Furthermore, the release of the complex incorporated in bovine
      serum albumin nanoparticles was also investigated in physiological conditions.
      The release of the complex followed a bi-phasic release pattern with high and low
      releasing rates at the first and second phases, respectively. Also, in order to
      obtain the binding mode of the Fe(III) complex with G-quadruplex, molecular
      modeling was performed. The molecular docking results showed that the Fe(III)
      complex was docked to the end-stacked of the G-quadruplex with a pi-pi
      interaction, created between the meloxicam ligand and the guanine bases of the G
      quadruplex.

PMID- 25563681
TI  - [Options for non-invasive assessment of liver fibrosis based on clinical data].
AB  - Liver cirrhosis is one of the leading causes of death worldwide. Liver biopsy is
      considered as the gold standard for the diagnosis of chronic liver diseases.
      Studies have focused on non-invasive markers for liver fibrosis because of the
      dangers and complications of liver biopsy. The authors review the non-invasive
      direct as well as indirect methods for liver fibrosis assessment and present the
      positive and negative predictive value, sensitivity and specificity of those.
      Clinical utilities of transient elastography (Fibrsocan) is also reviewed. Non
      invasive methods are useful in the assessment of liver fibrosis, monitoring
      disease progression and therapeutic response. Their accuracy can be increased by
      the combined or sequential use of non-invasive markers.

PMID- 25563679
TI  - Large external quality assessment survey on thrombin generation with CAT: further
      evidence for the usefulness of normalisation with an external reference plasma.
AB  - BACKGROUND: Calibrated Automated Thrombography (CAT) has been widely used to
      assess in vitro thrombin generation as an informative intermediary phenotype of
      coagulation. Interlaboratory exercises have documented a worrisome poor
      reproducibility. There are some data on the normalisation with an appropriate
      external reference plasma (RP). This multicentre study of the French-speaking CAT
      Club aimed at providing further evidence for the usefulness of such a
      normalisation. MATERIALS AND METHODS: Lyophilised aliquots of a RP along with 3
      plasmas (P1=normal; P2=hypo-; P3=hypercoagulable) were sent to 34 laboratories
      (corresponding to 38 instruments). CAT was studied using 1 and 5 pM tissue factor
      and other dedicated reagents. Normalisation with the local RP in use in the
      laboratory could also be performed. Interlaboratory CVs were calculated for each
      plasma before and after normalisation. RESULTS: Regarding endogenous thrombin
      potential, a good discrimination between the 3 plasmas was achieved in all
      laboratories but there was no overlap after normalisation only. CVs were
      generally not reduced with the use of local RP but were generally improved with
      normalisation using the external RP, often becoming lower than 10%. Regarding P2
      however, the benefit of normalisation was poor, and there were analytical
      difficulties as well, some laboratories being unable to get a useable signal.
      CONCLUSIONS: We confirm that normalisation of CAT results with a suitable
      external RP is useful in "real life" practice as it often permits an acceptable
      level of interlaboratory variability. In case of frank hypocoagulability, further
      improvements are required to get reliable, potentially clinically relevant
      results.

PMID- 25563682
TI  - [Clopidogrel resistance in cerebrovascular disease -- results of one-year follow
      up].
AB  - INTRODUCTION: In an earlier study the authors reported short-term benefits of
      clopidogrel treatment in patients with cerebrovascular disease. AIM: The aim of
      the authors was to analyze findings during a 12-month follow-up period. METHOD:
      100 patients with a history of acute stroke or transient ischaemic attack have
      been included in the study. The efficacy of the therapy was assessed 7 and 28
      days as well as 3, 6 and 12 months after initiation of medical therapy. Patients
      were divided into two parts (clopidogrel responder and resistant) based on their
      initial laboratory findings. Risk profiles, medical therapy, laboratory
      parameters and vascular events were compared between the two patient groups.
      RESULTS: After 7 days of treatment, clopidogrel seemed to be ineffective in 11
      patients (11%). Strong, clinically significant correlations were found among
      blood pressure values, blood glucose and lipid parameters, serum C-reactive
      protein levels and platelet aggregation levels. An aggressive secondary
      preventive therapy resulted in a decrease of clopidogrel resistance and
      improvement in laboratory parameters. Patients who were clopidogrel resistant at
      baseline had significantly higher rate of vascular events compared to those who
      were clopidogrel responders (18.1 vs. 4.5%, p<0.01), although clopidogrel
      resistance was not an independent risk factor of unfavourable vascular outcome
      using a multivariate analysis. No adverse events or hemorrhagic complications
      were observed. CONCLUSIONS: Clopidogrel resistance and unfavourable outcome seems
      to be associated with "classical" risk factors underlying the importance of
      aggressive secondary prevention.

PMID- 25563683
TI  - [Genetic and immune-toxicologic studies on abnormal thyroid functions in hospital
      employees exposed to cytostatic drugs].
AB  - INTRODUCTION: Environmental exposure to harmful chemicals may produce severe
      consequences. AIM: The aim of the authors was to perform geno- and immune
      toxicological monitoring in female employees occupationally exposed to cytostatic
      agents in hospitals and compare the findings to those obtained from controls.
      METHOD: Altogether 642 women working in hospital who were occupationally exposed
      to cytostatic drugs and 262 control women participated in the study. Frequency of
      chromosome aberrations, immune phenotype and activation of lymphocytes, and the
      production of reactive oxygen-species in neutrophil granulocytes were determined.
      RESULTS: Markedly higher number (n=39) of thyroid alterations was observed among
      exposed subjects as compared to controls (n=3). In persons with abnormal thyroid
      functions, the frequency of chromosome aberrations (3.69%) was significantly
      higher (3.69%) than in exposed subjects without thyroid alterations (2.43%) and
      in controls (1.70% and 1.60% in control subjects with and without thyroid
      alterations, respectively). Significantly increased ratio of helper T lymphocytes
      and decreased ratio of cytotoxic T cells and transferrin-receptor (CD71)
      expressing B cells were observed in exposed subjects having abnormal thyroid
      functions as compared to controls. In addition, the ratio of B cells, CD71
      expressing T cells and production of reactive oxygen-intermediates was
      significantly decreased in exposed subjects with thyroid alterations in
      comparison to exposed subjects without thyroid alterations. CONCLUSIONS: The
      results indicate increased geno- and immune-toxic effects among exposed subjects
      having thyroid alterations. Further data are needed to clearly establish the
      underlying pathophysiological mechanism of this finding.

PMID- 25563684
TI  - [The use of structural proximal tibial allografts coated with human albumin in
      treating extensive periprosthetic knee-joint bone deficiency and averting late
      complications. Case report].
AB  - The authors report the history of a 74-year-old patient who underwent surgical
      treatment for segmental knee-joint periprosthetic bone loss using structural
      proximal tibial allografts coated with serum albumin. Successful treatment of
      late complications which occurred in the postoperative period is also described.
      The authors emphasize that bone replacement with allografts is a physiological
      process that enables the stable positioning of the implant and the reconstruction
      of the soft tissues, the replacement of extensive bone loss, and also it is a
      less expensive operation. It has been already confirmed that treatment of
      lyophilised allografts with albumin improves the ability of bone marrow-derived
      mesenchymal stem cells to adhere and proliferate the surface of the allografts,
      penetrate the pores and reach deeper layers of the graft. Earlier studies have
      shown osteoblast activity on the surface and interior of the graft.

PMID- 25563685
TI  - [Gyorgy Diosadi Elekes' habilitation for privat-docentship in medical history in
      the Royal Hungarian Istvan Tisza University, Debrecen in 1941].

PMID- 25563687
TI  - Therapeutic uses of furin and its inhibitors: a patent review.
AB  - INTRODUCTION: Since the discovery of furin, numerous reports have studied its
      role in health and diseases, including cancer, inflammatory and infectious
      diseases. This interest has led to the development of both large protein- and
      peptide-based inhibitors aiming to control furin activity to treat these
      disorders. The most recent advances include the development of potent
      peptidomimetic furin inhibitors, considerably expanding the field of therapeutic
      applications. AREA COVERED: In this review, the use of furin or its inhibitors
      for therapeutic conditions is described through the patent literature since 1994.
      Only compounds with biological efficacy or augmented properties demonstrated
      within the patent literature or the associated publications concerning their
      claimed uses are discussed. EXPERT OPINION: Considering the diseases that may
      benefit from furin inhibition, several patents detail the use of the restricted
      number of furin inhibitors. However, there have been recent reports of new
      scaffolds, and even the use of furin itself, as a therapeutic agent. Despite
      considerable evidence of in vivo efficacy, limited confirmation from clinical
      trials supports or refutes the further use of these compounds in a therapeutic
      context. The most advanced application is the use of furin knockdown in the
      generation of an autologous cancer vaccine, which has initiated clinical trials.

PMID- 25563688
TI  - The impact of polystyrene microplastics on feeding, function and fecundity in the
      marine copepod Calanus helgolandicus.
AB  - Microscopic plastic debris, termed "microplastics", are of increasing
      environmental concern. Recent studies have demonstrated that a range of
      zooplankton, including copepods, can ingest microplastics. Copepods are a
      globally abundant class of zooplankton that form a key trophic link between
      primary producers and higher trophic marine organisms. Here we demonstrate that
      ingestion of microplastics can significantly alter the feeding capacity of the
      pelagic copepod Calanus helgolandicus. Exposed to 20 MUm polystyrene beads (75
      microplastics mL(-1)) and cultured algae ([250 MUg C L(-1)) for 24 h, C.
      helgolandicus ingested 11% fewer algal cells (P = 0.33) and 40% less carbon
      biomass (P < 0.01). There was a net downward shift in the mean size of algal prey
      consumed (P < 0.001), with a 3.6 fold increase in ingestion rate for the smallest
      size class of algal prey (11.6-12.6 MUm), suggestive of postcapture or
      postingestion rejection. Prolonged exposure to polystyrene microplastics
      significantly decreased reproductive output, but there were no significant
      differences in egg production rates, respiration or survival. We constructed a
      conceptual energetic (carbon) budget showing that microplastic-exposed copepods
      suffer energetic depletion over time. We conclude that microplastics impede
      feeding in copepods, which over time could lead to sustained reductions in
      ingested carbon biomass.

PMID- 25563689
TI  - A toy model for nucleus-sized crowding confinement.
AB  - We conduct Monte Carlo simulations to understand the spatial distribution of a
      polymer molecule confined within a rigid spherical capsule under crowding
      conditions, via a bead-spring chain model. To adjust the crowding level, the
      polymer is mixed with spherical crowders. As the interior of the capsule becomes
      more crowded, chain monomers tend to move to the capsule boundary under the
      penalty of conformational entropy. By incorporating some attraction between
      monomers and crowders, the polymer chain moves away from the capsule boundary.
      The interplay, between the conformational entropy, DNA-protein interaction, and
      molecular crowding induced depletion force between the chain and capsule
      boundary, may be essential to elucidate the heterogeneous chromatin structure in
      nuclei. Furthermore, the effects of chain length and size disparity between the
      monomers and the crowders are also investigated preliminarily. 

PMID- 25563690
TI  - A novel fluidic control method for nanofluidics by solvent-solvent interaction in
      a hybrid chip.
AB  - The fluidic control method is a fundamental technology for the development of
      nanofluidics. In this report, an organic phase was driven to flow inside the
      nanochannel because of its dissolution into an aqueous phase. With selective
      modification, a stable organic/aqueous interface was generated at the junction of
      the micro/nanochannels in a hybrid chip. The aqueous phase was kept flowing in
      the microchannel, and the organic phase in the nanochannel dissolved into the
      aqueous phase through the interface and produced a flow inside the nanochannel.
      This method is simple, easy to control and requires no specific equipment.
      Importantly, the flow is driven by the surface tension in a controllable manner,
      which will not be affected by the depth of the nanochannel. This method can be a
      useful alternative to the present fluidic control methods in nanofluidics. 

PMID- 25563691
TI  - Early achievement of complete renal response predicts good long-term renal
      outcome and low systemic damage in newly diagnosed lupus nephritis class III or
      IV.
AB  - OBJECTIVE: To identify predictors of long-term renal prognosis after induction
      therapy in patients with newly diagnosed lupus nephritis class III or IV.
      METHODS: We retrospectively studied patients with newly diagnosed lupus nephritis
      class III or IV. We divided them into two groups according to the complete renal
      response (CR) status at 3 years after induction therapy. We compared baseline
      clinical characteristics, renal pathological findings, and time to achieve CR,
      and identified predictors. Patients were followed up for to 10 years to assess
      long-term systemic damage. RESULTS: Eighteen patients with CR and 9 with non-CR
      were included. There were no significant differences in baseline characteristics.
      Early CR, which was defined as achieving CR at 3 months after induction therapy,
      was significantly associated with maintaining CR at 3 years (p = 0.012). Patients
      with early CR less frequently had flare in systemic manifestation compared with
      those without over 10 years (p = 0.026). Deterioration of systemic damage was
      observed more often in non-early CR patients than early CR patients at 10 years
      (p = 0.029). CONCLUSION: Achieving CR at 3 months after induction therapy may
      predict CR at 3 years, reduced organ damage, and a low incidence of disease flare
      for 10 years.

PMID- 25563692
TI  - Development of a geometrically accurate and adaptable finite element head model
      for impact simulation: the Naval Research Laboratory-Simpleware Head Model.
AB  - This study demonstrates a novel model generation methodology that addresses
      several limitations of conventional finite element head models (FEHM). By
      operating chiefly in image space, new structures can be incorporated or merged,
      and the mesh either decimated or refined both locally and globally. This
      methodology is employed in the development of a highly bio-fidelic FEHM from high
      resolution scan data. The model is adaptable and presented here in a form
      optimised for impact and blast simulations. The accuracy and feasibility of the
      model are successfully demonstrated against a widely used experimental benchmark
      in impact loading and through the investigation of potential brain injury under
      blast overpressure loading. 

PMID- 25563693
TI  - Toxicity of metal oxide nanoparticles in Escherichia coli correlates with
      conduction band and hydration energies.
AB  - Metal oxide nanoparticles (MOx NPs) are used for a host of applications, such as
      electronics, cosmetics, construction, and medicine, and as a result, the safety
      of these materials to humans and the environment is of considerable interest. A
      prior study of 24 MOx NPs in mammalian cells revealed that some of these
      materials show hazard potential. Here, we report the growth inhibitory effects of
      the same series of MOx NPs in the bacterium Escherichia coli and show that
      toxicity trends observed in E. coli parallel those seen previously in mammalian
      cells. Of the 24 materials studied, only ZnO, CuO, CoO, Mn2O3, Co3O4, Ni2O3, and
      Cr2O3 were found to exert significant growth inhibitory effects; these effects
      were found to relate to membrane damage and oxidative stress responses in minimal
      trophic media. A correlation of the toxicological data with physicochemical
      parameters of MOx NPs revealed that the probability of a MOx NP being toxic
      increases as the hydration enthalpy becomes less negative and as the conduction
      band energy approaches those of biological molecules. These observations are
      consistent with prior results observed in mammalian cells, revealing that
      mechanisms of toxicity of MOx NPs are consistent across two very different taxa.
      These results suggest that studying nanotoxicity in E. coli may help to predict
      toxicity patterns in higher organisms.

PMID- 25563694
TI  - Measures of obesity and risk of Crohn's disease and ulcerative colitis.
AB  - BACKGROUND: Obesity is associated with intestinal-specific inflammation.
      Nonetheless, a specific role of obesity in the etiology of inflammatory bowel
      disease is unclear. METHODS: We conducted a prospective cohort study of U.S.
      women enrolled in 1989 in the Nurses' Health Study II. At baseline, we collected
      information on height, weight, waist and hip circumference, weight at age 18, and
      body shape at age 20. We used Cox proportional hazard models to calculate hazard
      ratios and 95% confidence intervals (CIs). RESULTS: Among 111,498 women (median
      age, 35 yr), we documented 153 cases of Crohn's disease (CD) and 229 cases of
      ulcerative colitis (UC) more than 18 years of follow-up, encompassing 2,028,769
      person-years. Compared with women with normal BMI, the multivariate-adjusted
      hazard ratios of CD were 2.33 (95% CI, 1.15-4.69) for obese women at age 18 and
      1.58 (95% CI, 1.01-2.47) for obese women at baseline. Increasing weight gain
      between age 18 and baseline was associated with increased risk of CD (Ptrend =
      0.04). Adolescent body habitus was also associated with risk of CD with a
      multivariate-adjusted hazard ratio of CD of 1.63 (95% CI, 1.07-2.50) for women
      with overweight/obese body shape compared with women with a thin/slender body
      shape. We did not observe a significant association between any of these
      anthropometric measures and risk of UC. CONCLUSIONS: In a large prospective
      cohort of U.S. women, measures of adiposity were associated with an increased
      risk of CD but not UC. Additional studies are needed to elucidate the biological
      mechanisms by which excess adiposity may increase the risk of CD.

PMID- 25563697
TI  - Monitoring the coordination of amine ligands on silver nanoparticles using NMR
      and SERS.
AB  - Low size dispersity silver nanoparticles (ca. 6 nm) have been synthesized by the
      hydrogenolysis of silver amidinate in the presence of hexadecylamine. Combining
      NMR techniques with SERS and DFT modeling, it is possible to observe an original
      stabilization mechanism. Amidine moiety is strongly coordinated to the Ag(0)
      nanoparticles surface whereas HDA ligand is necessary to prevent agglomeration,
      although it is only weakly interacting with the surface. 

PMID- 25563698
TI  - The physics of chromatin.

PMID- 25563699
TI  - Thermodynamic model of heterochromatin formation through epigenetic regulation.
AB  - Gene regulation in eukaryotes requires the segregation of silenced genomic
      regions into densely packed heterochromatin, leaving the active genes in
      euchromatin regions more accessible. We introduce a model that connects the
      presence of epigenetically inherited histone marks, methylation at histone 3
      lysine-9, to the physical compaction of chromatin fibers via the binding of
      heterochromatin protein 1 (HP1). Our model demonstrates some of the key physical
      features that are necessary to explain experimental observations. In particular,
      we demonstrate that strong cooperative interactions among the HP1 proteins are
      necessary to see the phase segregation of heterochromatin and euchromatin
      regions. We also explore how the cell can use the concentration of HP1 to control
      condensation and under what circumstances there is a threshold of methylation
      over which the fibers will compact. Finally, we consider how different potential
      in vivo fiber structures as well as the flexibility of the histone 3 tail can
      affect the bridging of HP1. Many of the observations that we make about the HP1
      system are guided by general thermodynamics principles and thus could play a role
      in other DNA organizational processes such as the binding of linker histones. 

PMID- 25563695
TI  - Cytokines, IBD, and colitis-associated cancer.
AB  - Inflammatory bowel diseases (IBDs) are debilitating conditions that result in
      intestinal damage due to chronic inflammation. In addition, the perpetual state
      of inflammation predisposes individuals to the development of colitis-associated
      cancer. Because of the immense immune cell infiltration into colon, cytokines
      produced by immune cells are major players in the initiation and progression of
      IBD and colitis-associated cancer. In this review, we will explore the functions
      of many key cytokines and their roles in IBD and colitis-associated cancer, as
      well as their influences on the immune system and stromal cells. Finally, we will
      briefly discuss current therapies and current clinical trials targeting cytokines
      in IBD.

PMID- 25563700
TI  - Same-sex couples matter in cancer care.

PMID- 25563701
TI  - Patient cost sharing and receipt of erythropoiesis-stimulating agents through
      medicare part D.
AB  - PURPOSE: Medicare Part D prescription benefits cover injected medications,
      normally covered under Part B, when administered outside of physician offices.
      Erythropoiesis-stimulating agents (ESAs) used for chronic anemia management in
      patients with myelodysplastic syndromes (MDS) are commonly injected in a
      physician office but can be administered safely at home. In this study, we
      explored out-of-pocket (OOP) costs and receipt of Part D-covered ESAs in Medicare
      beneficiaries with MDS. MATERIALS AND METHODS: Patients with MDS enrolled in
      Medicare Parts A, B, and D were identified using diagnosis codes from 100% claims
      from 2006 to 2008. OOP costs for the mean erythropoietin alfa claim were compared
      for Parts B and D. Multivariable models examined the effect of low-income subsidy
      (LIS) and other Part D cost sharing on receipt of any ESA and any Part D-covered
      ESA. RESULTS: A total of 13,117 (62.9%) of 20,848 patients received ESAs, but
      only 1,436 (6.9%) had any Part D claim. OOP payment was $348 under Part D versus
      $161 under Part B. Among patients with ESA use, those with LIS were 4* more
      likely to receive Part D ESAs (P < .01). CONCLUSION: Few patients with MDS
      received ESAs through Part D. OOP payments required under Part D were
      substantially higher than under Part B. Cost sharing, as reflected by LIS
      receipt, likely affected decisions to prescribe ESAs outside of the physician
      office. Improved coordination between Part B and D benefits regarding issues of
      home injection of medications may create incentives that improve patient access
      and convenience and reduce costs associated with administration.

PMID- 25563702
TI  - Hospitalists on an inpatient tertiary care oncology teaching service.
AB  - PURPOSE: Hospitalists provide quality care in various inpatient settings, but the
      ability of hospitalists to provide quality inpatient care for patients with
      complex cancer has not been studied. This study explores outcomes with a
      hospitalist-led versus medical oncologist-led house staff team on an inpatient
      medical GI oncology teaching service. METHODS: This observational retrospective
      cohort study examined 829 patient discharges from August 2012 to January 2013 on
      the GI oncology inpatient teaching service at Memorial Sloan Kettering Cancer
      Center, a tertiary cancer center in New York, New York. We compared average
      length of stay (ALOS), 30-day readmission rates, establishment of new do not
      resuscitate (DNR) orders, nosocomial pneumonia and urinary tract infection (UTI)
      rates, radiographic and laboratory tests per patient, and disposition on
      discharge between hospitalist-led and oncologist-led teams. RESULTS: Median years
      of clinical experience was 6 (range, 4 to 9 years) for hospitalists and 7 (range,
      0.5 to 36 years) for oncologists. ALOS (hospitalist led, 5.6 v oncologist led,
      5.2 days; P = .30), readmission within 30 days (hospitalist led, 14% v oncologist
      led, 16%; P = .44), new DNR orders (hospitalist led, 18% v oncologist led, 19%; P
      = .90), nosocomial pneumonia (hospitalist led, 0.5% v oncologist led, 0.7%; P =
      .63) and UTI rates (hospitalist led, 0.5% v oncologist led, 0.7%; P = .63),
      number of radiographic studies and laboratory tests, and disposition on discharge
      were not significantly different between groups. CONCLUSION: A hospitalist-led
      inpatient service with house staff represents a novel approach for caring for
      hospitalized GI oncology patients with cancer.

PMID- 25563703
TI  - Correlation of clinical stage and performance status with quality of life in
      patients seen in a pancreas multidisciplinary clinic.
AB  - INTRODUCTION: The objectives of this study were to evaluate quality of life (QoL)
      in patients presenting to the Johns Hopkins Pancreas Multidisciplinary Clinic
      (PMDC), and to examine associations between disease status, performance status,
      and QoL in order to identify patient subgroups that are most at risk for reduced
      QoL. PATIENTS AND METHODS: Data from 77 patients were evaluated. At initial
      presentation, disease and performance status were assessed, as well as QoL, which
      was obtained with the European Organisation for Research and Treatment of Cancer
      QLQ-PAN26 questionnaire. Statistical analyses examined associations between QoL,
      disease status, and performance status. RESULTS: Digestive symptoms (P < .003)
      significantly differed by pancreatic disease status (resectable, resected,
      locally advanced, and metastatic). Patients with a worse performance status,
      defined as Eastern Cooperative Oncology Group >= 1, were more likely to report
      symptomatic pancreatic pain (P = .001), digestive symptoms (P = .017), cachexia
      (P = .004), and ascites (P < .001) compared with patients with a performance
      status of 0. The majority (92%) of patients reported a significant fear of future
      health problems, regardless of disease status or performance status. CONCLUSION:
      Although several measures of QoL have been observed in all patients, certain
      measures appear to correlate specifically with worse disease status. Therefore,
      routine assessment of QoL is suggested in order to guide treatment decisions.
      Further investigation on optimizing the use of QoL measures and patient-reported
      outcomes to better tailor management is warranted.

PMID- 25563704
TI  - A minor conformation of a lanthanide tag on adenylate kinase characterized by
      paramagnetic relaxation dispersion NMR spectroscopy.
AB  - NMR relaxation dispersion techniques provide a powerful method to study protein
      dynamics by characterizing lowly populated conformations that are in dynamic
      exchange with the major state. Paramagnetic NMR is a versatile tool for
      investigating the structures and dynamics of proteins. These two techniques were
      combined here to measure accurate and precise pseudocontact shifts of a lowly
      populated conformation. This method delivers valuable long-range structural
      restraints for higher energy conformations of macromolecules in solution. Another
      advantage of combining pseudocontact shifts with relaxation dispersion is the
      increase in the amplitude of dispersion profiles. Lowly populated states are
      often involved in functional processes, such as enzyme catalysis, signaling, and
      protein/protein interactions. The presented results also unveil a critical
      problem with the lanthanide tag used to generate paramagnetic relaxation
      dispersion effects in proteins, namely that the motions of the tag can interfere
      severely with the observation of protein dynamics. The two-point attached CLaNP-5
      lanthanide tag was linked to adenylate kinase. From the paramagnetic relaxation
      dispersion only motion of the tag is observed. The data can be described
      accurately by a two-state model in which the protein-attached tag undergoes a 23
      degrees  tilting motion on a timescale of milliseconds. The work demonstrates the
      large potential of paramagnetic relaxation dispersion and the challenge to
      improve current tags to minimize relaxation dispersion from tag movements. 

PMID- 25563705
TI  - Traumatic optic neuropathy: facial CT findings affecting visual acuity.
AB  - The purpose of this study was to determine the relationship between admission
      visual acuity (VA) and facial computed tomographic (CT) findings of traumatic
      optic neuropathy (TON). We retrospectively evaluated CT findings in 44 patients
      with TON. Mid-facial fractures, extraconal and intraconal hematomas, hematomas
      along the optic nerve and the posterior globe, optic canal fracture, nerve
      impingement by optic canal fracture fragment, and extraconal and intraconal
      emphysema were evaluated. CT variables of patients with and without available VA
      were compared. VA was converted into logarithm of the minimum angle of resolution
      (logMAR) to provide a numeric scale for the purpose of statistical analysis. The
      risk factors related to poor VA on univariate analysis were as follows:
      intraconal hematoma [median logMAR -4.7 versus -1.15, p = 0.016] and hematoma
      along the optic nerve [median -4.7 versus -1.3, p = 0.029]. Intraconal hematoma
      was the best predictor of poor VA (coefficient, 1.01; SE, 0.34; and p = 0.008).
      Receiver operating characteristic (ROC) curve analysis showed that the presence
      of intraconal hematoma and hematoma along the optic nerve predicted poor VA
      (logMAR of -3.7 or lower) with an area under the curve of 0.8 and 0.85,
      respectively. TON patients at higher risk of severe visual impairment may be
      identified based on admission facial CT. 

PMID- 25563707
TI  - Surgical strategy for aortic prosthetic graft infection with (18)F
      fluorodeoxyglucose positron emission tomography/computed tomography.
AB  - A 30-year-old man with Marfan syndrome who underwent Crawford type II extension
      aneurysm repair about 9 years ago was referred to our hospital with persistent
      fever. Computed tomography (CT) showed air around the mid-descending aortic
      prosthetic graft. Because the air did not disappear in spite of intravenous
      antibiotics, (18)F-fluorodeoxyglucose positron emission tomography/computed
      tomography (FDG-PET/CT) was performed. FDG-PET/CT revealed four high-uptake
      lesions. After dissecting the aortic graft particularly focusing on the high
      uptake lesions, this patient underwent in situ graft re-replacement of descending
      aortic graft with a rifampicin-bonded gelatin-impregnated Dacron graft and
      omentopexy. The patient remains well without recurrent infection at 3 months
      after surgery. 

PMID- 25563706
TI  - Long-term follow-up of homoharringtonine plus all-trans retinoic acid-based
      induction and consolidation therapy in newly diagnosed acute promyelocytic
      leukemia.
AB  - We conducted a retrospective study to evaluate the efficacy of combining
      homoharringtonine (HHT) with all-trans-retinoic acid (ATRA)-based induction
      therapy, followed by three courses of consolidation chemotherapy and 2-year
      sequential maintenance therapy in acute promyelocytic leukemia (APL). Fifty-three
      patients were enrolled in the study. The complete remission (CR) rate was 100 %.
      No patient died during induction therapy. The 9-year event-free survival (EFS)
      and 9-year overall survival (OS) for all patients were 79.0 and 83.0 %,
      respectively. Outcome estimates according to the body mass index (BMI) were
      carried out. Twenty-three (43.4 %) were underweight/normal (BMI < 23.0 kg/m(2)),
      whereas 30 patients (56.6 %) were overweight/obese (BMI >= 23.0 kg/m(2)).
      Underweight/normal-weight patients had a 9-year OS of 100 %, compared with 73.0 %
      for overweight/obese patients (P = 0.044). These results indicate that HHT plus
      ATRA-based induction and consolidation therapy may be a highly efficacious
      treatment option for newly diagnosed APL. Increased BMI had an adverse prognostic
      impact in APL.

PMID- 25563708
TI  - Atrial fibrillation in cardiac resynchronization recipients with and without
      prior arrhythmic history. How much of arrhythmia is too much?
AB  - BACKGROUND: The aim of the study was to assess long-term incidence of atrial
      fibrillation (AF) in cardiac resynchronization (CRT) recipients with and without
      prior arrhythmic history, factors predisposing to arrhythmia, as well as to
      evaluate the prognostic power of cumulative arrhythmia burden, duration of the
      longest episode and the number of episodes. METHODS: Device-collected data on AF
      episodes during 24 months in 96 participants of a randomized CRT-trial were
      analyzed (15% in NYHA class IV, sinus rhythm, median left ventricular ejection
      fraction 24% and QRS 169 ms). Blindly adjudicated major adverse cardiac events
      (MACE) and any-cause death were censoring variables. RESULTS: Two-year incidence
      of AF was 70%, including 66% of patients without previous AF history. No baseline
      characteristics distinguished those who developed new onset AF. Percent of time
      spent in AF, but not number of episodes predicted mortality (adjusted hazard
      ratio [HR] 1.05 +/- 95% confidence interval CI 1.01-1.10) and MACE incidence (HR
      1.03 +/- 1.01-1.07; p = 0.03). Duration of the longest episode also predicted
      mortality (HR 1.06 +/- 1.01-1.12; both p = 0.03). Prognostic impact of AF load
      was marked only in patients with slower ventricular response (< 98/min), but was
      independent from CHADS2 scores, pacing burden, or prior atrioventricular nodal
      ablation. CONCLUSIONS: Seven out of 10 CRT-patients had AF within 2 years,
      including two-thirds of subjects without arrhythmic history. No baseline features
      distinguished those who developed new onset AF. Arrhythmia burden and duration of
      the longest episode, but not number of episodes influenced outcomes in CRT
      patients, irrespectively from pacing burden or prior atrioventricular node
      ablation.

PMID- 25563709
TI  - Comparison of body mass index and body surface area as outcome predictors in
      patients with systolic heart failure.
AB  - BACKGROUND: We investigated whether the 'obesity paradox' in heart failure (HF)
      is influenced by common confounders, and assessed if body surface area (BSA) may
      correlate more closely than body mass index (BMI) with prognosis. METHODS: We
      studied 630 systolic HF patients at their initial visit to the HF clinic. Body
      size was measured by BMI and BSA. The association between body indices and
      mortality was assessed by Cox proportional-hazard analyses. RESULTS: There were
      248 deaths during mean follow-up of 39 months. A progressive inverse association
      of BMI and BSA tertiles (T1-T3) with mortality risk was observed (for BSA: T3,
      reference, T2, hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.01-1.95, p
      = 0.04 and T1, HR = 1.78, 95% CI 1.29-2.45, p < 0.001; for BMI: T3, reference,
      T2, HR = 1.29, 95% CI 0.92-1.79, p = 0.13 and T1, HR = 1.66, 95% CI 1.21-2.27, p
      = 0.002). The obesity paradox was attenuated after multivariate adjustment, and
      did not persist after adjustment for age alone (for BMI: T3, reference, T2, HR =
      1.13, 95% CI 0.81-1.58, p = 0.47; T1, HR = 1.30, 95% CI 0.94-1.80, p = 0.12; for
      BSA: T3, reference, T2, HR = 0.96, 95% CI 0.68-1.35, p = 0.82; T1, HR = 1.15, 95%
      CI 0.82-1.63, p = 0.42). CONCLUSIONS: BSA provides prognostic information similar
      to BMI in systolic HF. However, the obesity paradox of both BMI and BSA in HF may
      be confounded by the younger age of the obese patients.

PMID- 25563710
TI  - Cryoballoon ablation of atrial fibrillation: How important is the proper
      selection of patients?
AB  - BACKGROUND: Relation between pre-procedural selection of patients and the success
      rate after a single cryoballoon ablation (CAB) procedure is unknown. METHODS: CAB
      was performed in 378 (65% male, median age 58 years, 85% paroxysmal atrial
      fibrillation [AF]) consecutive patients with symptomatic and drug refractory AF.
      The combined ALARMEc (Atrial fibrillation type, Left Atrium size, Renal
      insufficiency, Metabolic syndrome, cardiomyopathy) risk score was calculated for
      each individual patient. The end-point of the study was the first AF, atrial
      flutter or atrial tachycardia recurrence after the 3-month blanking period in the
      1-year follow-up since the index procedure, in the absence of anti-arrhythmic
      (class I and III) therapy. RESULTS: Single and multi-catheter approach was used
      in 79% and 21% of patients, respectively. The acute success rate with single and
      multi-catheter approach was 79% and 99%, respectively. The overall 1-year success
      rate after a single CAB procedure was 70%. The 1-year outcome was: 83%, 70%, 60%,
      40% and 29% in patients with ALARMEc risk score: 0, 1, 2, 3 and 5, respectively.
      Total rate of complications was 11%, including transient phrenic nerve palsy in
      9.5% of cases. CONCLUSIONS: Multi-catheter approach was needed in 21% of patients
      to achieve acute pulmonary vein isolation. Patients with low (<= 1) ALARMEc risk
      score, preferably young individuals with sole paroxysmal AF (ALARMEc = 0), are
      best candidates for CBA procedure. Performing CBA in patients with higher (> 2)
      ALARMEc risk score should be avoided. Phrenic nerve palsy was a transient
      complication.

PMID- 25563711
TI  - Effect of angiotensin converting enzyme inhibitors on periprocedural myocardial
      infarction in patients with metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome (MetS) has been reported as a risk factor for
      cardiovascular events. The aim of the present study is to investigate the
      association between chronic angiotensin-converting enzyme inhibitors (ACE-I)
      therapy and the rate of periprocedural myocardial infarction (PMI) after elective
      coronary stenting among patients with MetS. METHODS: The inclusion criteria were
      MetS and plan for elective percutaneous coronary intervention. To assess the
      effect of ACE-I treatment on the incidence of PMI, measurements of cardiac
      biomarkers (CK-MB mass and troponin I) were performed at baseline and 24 h after
      the procedure. RESULTS: A total of 459 patients fulfilling the inclusion criteria
      were recruited to chronic ACE-I treatment and ACE-I naive groups in a 2/1 ratio.
      Baseline troponin I and CK-MB levels were similar in both treatment groups,
      whereas they were significantly lower in ACE-I group 24 h after the procedure.
      Univariate analysis identified body mass index (BMI), LDL cholesterol, nitrate
      and ACE-I use as significant factors for the development of PMI. Multivariate
      regression model revealed that body mass index increased and use of nitrate and
      ACE-I decreased the probability of PMI independent from confounding factors (OR
      1.14, 95% CI 1.05-1.23, p = 0.002 for BMI; OR 0.26, 95% CI 0.14-0.48, p = 0.01
      for nitrate use, OR 0.51, 95% CI 0.27-0.93, p = 0.03 for ACE-I use). CONCLUSIONS:
      This prospective observational cohort trial demonstrated that chronic ACE-I
      therapy was an independent predictor for reduced PMI among patients with MetS who
      underwent elective coronary intervention.

PMID- 25563712
TI  - Systemic or local thrombolysis in high-risk pulmonary embolism.
AB  - BACKGROUND AND AIM: High-risk pulmonary embolism (PE) represents an important
      health problem in emergency cardiology, being associated with a high rate of
      mortality. The aim of this study is to assess the efficacy and safety of
      pulmonary intra-arterial thrombolysis with streptokinase compared to systemic
      thrombolysis. METHODS AND RESULTS: In our study, 28 patients with acute high risk
      PE were treated by intra-arterial thrombolysis with clinical success rate of
      96.4%, while in the group with systemic thrombolysis (24 patients) the rate of
      clinical success was significantly lower (70.8%). Also, pressure gradient between
      right ventricle (RV) and right atrial (RA) (PRV-RA) decreased significantly in
      patients treated by pulmonary intra-arterial thrombolysis instead of systemic
      thrombolysis. Mortality during the hospitalization was 0% in the group with local
      thrombolysis and 29.2% in the other group, with a significant statistical
      difference. Major bleeding complications appeared in 14.3% of the patients with
      local thrombolysis and in 20.8% of the ones treated by systemic thrombolysis,
      without statistical significance. Moreover, the proportion of minor bleeding was
      comparable in the two groups of patients. There was no intracranial bleeding.
      Disseminated intravascular coagulation occurred in 1 patient with systemic
      thrombolysis. CONCLUSIONS: The rate of clinical success and the regression of RV
      overload were significantly higher in patients treated by pulmonary intra
      arterial thrombolysis. The results regarding the efficiency of the pulmonary
      intra-arterial thrombolysis in high-risk PE are encouraging, the mortality in
      these patients being significantly lower than the one for systemic administration
      of the thrombolytic agent.

PMID- 25563713
TI  - The reliability of retro-cues determines the fate of noncued visual working
      memory representations.
AB  - Retrospectively cueing an item retained in visual working memory during
      maintenance is known to improve its retention. However, studies have provided
      conflicting results regarding the costs of such retro-cues for the noncued items,
      leading to different theories on the mechanisms behind visual working memory
      maintenance and retro-cueing. Here we tested an alternative explanation of the
      conflicting results regarding retro-cue costs-namely, that they are caused at
      least partly by differences in retro-cue reliability. We manipulated the ratio of
      valid-cue trials to invalid-cue trials within blocks. We used a continuous-report
      procedure that allowed fitting a model that provided recall probability and
      precision estimates for the memory representations. Reconciling previous
      contradictory findings, benefits for valid cues were observed in all conditions,
      but invalid cueing costs were found only when the retro-cue had a high
      reliability (i.e., was 80 % valid), but not when it had a lower reliability
      (i.e., 50 % valid). This was found for both the recall probability and the
      precision of visual working memory representations. Our results suggest that the
      cognitive mechanisms underlying retro-cue effects are strategically adjusted by
      participants, depending on the perceived retro-cue reliability.

PMID- 25563714
TI  - A randomised double-blind placebo-controlled 12- week feasibility trial of
      methotrexate added to treatment as usual in early schizophrenia: study protocol
      for a randomised controlled trial.
AB  - BACKGROUND: Methotrexate is a commonly used anti-inflammatory and
      immunosuppressive drug. There is growing evidence that inflammatory processes are
      involved in the pathogenesis of schizophrenia. In our recent randomised double
      blind placebo-controlled clinical trial in Pakistan and Brazil, the addition of
      minocycline (antibiotic and anti-inflammatory drug) for 1 year to treatment as
      usual reduced negative symptoms and improved some cognitive measures. A meta
      analysis of cytokine changes in the peripheral blood has identified IL-2, IFN
      gamma, TNF-alpha and soluble IL-2 receptor as trait markers of schizophrenia
      because their levels were elevated during acute exacerbations and reduced in
      remission. This suggests immune activation and an inflammatory syndrome in
      schizophrenia. Based on the evidence of the strong anti-inflammatory properties
      of methotrexate, we propose that low-dose methotrexate may be an effective
      therapy in early schizophrenia. METHODS/DESIGN: This is a double-blind placebo
      controlled study of methotrexate added to treatment as usual for patients
      suffering from schizophrenia, schizoaffective disorder, psychosis not otherwise
      specified or schizophreniform disorder. This will be with 72 patients, 36 in each
      arm over 3 months. There will be screening, randomisation and follow-up visits.
      Full clinical assessments will be carried out at baseline, 2, 4, 8 and 12 weeks.
      Social and cognitive assessments will be carried out at baseline and 12 weeks.
      Methotrexate will be given at a dose of 10 mgs orally once a week for a 3-month
      period. DISCUSSION: Evidence suggests inflammatory processes are involved in the
      pathogenesis of schizophrenia and anti-inflammatory treatments have shown to have
      some beneficial effects. Methotrexate is a known immunosuppressant and anti
      inflammatory drug. The aim of this study is to establish the degree of
      improvement in positive and negative symptoms, as well as cognitive functioning
      with the addition of methotrexate to treatment as usual.ClinicalTrials.gov
      identifier: NCT02074319 (24 February 2014).

PMID- 25563715
TI  - The effect of different concentrations of copper and lead on the morphology and
      physiology of Hypnea musciformis cultivated in vitro: a comparative analysis.
AB  - Copper and lead, as remnants of industrial activities and urban effluents, have
      heavily contaminated many aquatic environments. Therefore, this study aimed to
      determine their effects on the physiological, biochemical, and cell organization
      responses of Hypnea musciformis under laboratory conditions during a 7-day
      experimental period. To accomplish this, segments of H. musciformis were exposed
      to photosynthetic active radiation at 80 MUmol photons m(-2) s(-1), Cu (0.05 and
      0.1 mg kg(-1)), and Pb (3.5 and 7 mg kg(-1)). Various intracellular abnormalities
      resulted from exposure to Cu and Pb, including a decrease in phycobiliproteins.
      Moreover, carotenoid and flavonoid contents, as well as phenolic compounds, were
      decreased, an apparent reflection of chemical antioxidant defense against
      reactive oxygen species. Treatment with Cu and Pb also caused an increase in the
      number of floridean starch grains, probably as a defense against nutrient
      deprivation. Compared to plants treated with lead, those treated with copper
      showed higher metabolic and ultrastructural alterations. These results suggest
      that H. musciformis more readily internalizes copper through transcellular
      absorption. Finally, as a result of ultrastructural damage and metabolic changes
      observed in plants exposed to different concentrations of Cu and Pb, a
      significant reduction in growth rates was observed. Nevertheless, the results
      indicated different susceptibility of H. musciformis to different concentrations
      of Cu and Pb.

PMID- 25563716
TI  - A case of miliary pulmonary cryptococcosis and review of literature.
AB  - We describe a case of cryptococcal fungemia in a 62-year-old male renal
      transplant patient. The diagnosis was established by isolation of Cryptococcus
      neoformans using the Isolator((r)) blood culture lysis-centrifugation system.
      Testing for cryptococcal antigens was negative in the serum and cerebrospinal
      fluid. Transbronchial lung biopsies and bronchoalveolar lavage were negative.
      Antifungal therapy with fluconazole was started, resulting in fever remission,
      and a sustained clinical response was achieved. The literature on miliary
      pulmonary cryptococcosis is reviewed, and three similar cases were previously
      reported with disseminated cryptococcosis that resembled miliary tuberculosis on
      imaging. These emphasize the importance of eliminating causes other than
      tuberculosis in patients presenting with miliary pulmonary disease, even in
      countries with a high prevalence of tuberculosis. 

PMID- 25563717
TI  - Expression and bioregulation of the kallikrein-related peptidases family in the
      human neutrophil.
AB  - The family of kallikrein-related peptidases (KLKs) has been identified in a
      variety of immunolabeled human tissue sections, but no previous study has
      experimentally confirmed their presence in the human neutrophil. We have
      investigated the expression and bioregulation of particular KLKs in the human
      neutrophil and, in addition, examined whether stimulation by a kinin B(1)
      receptor (B1R) agonist or fMet-Leu-Phe (fMLP) induces their secretion. Western
      blot analysis of neutrophil homogenates indicated that the MM of the KLKs ranged
      from 27 to 50 kDa. RT-PCR showed that blood neutrophils expressed only KLK1,
      KLK4, KLK10, KLK13, KLK14 and KLK15 mRNAs, whereas the non-differentiated HL-60
      cells expressed most of them, with exception of KLK3 and KLK7. Nevertheless,
      mRNAs for KLK2, KLK5, KLK6 and KLK9 that were previously undetectable appeared
      after challenging with a mixture of cytokines. Both kinin B(1)R agonist and fMLP
      induced secretion of KLK1, KLK6, KLK10, KLK13 and KLK14 into the culture medium
      in similar amounts, whereas the B(1)R agonist caused the release of lower amounts
      of KLK2, KLK4 and KLK5. When secreted, the differing proteolytic activity of KLKs
      provides the human neutrophil with a multifunctional enzymatic capacity
      supporting a new dimension for its role in human disorders of diverse etiology.

PMID- 25563718
TI  - Effect of platinum-based chemotherapy for non-small cell lung cancer patients
      with interstitial lung disease.
AB  - PURPOSE: The prognosis of non-small cell lung cancer (NSCLC) patients with
      interstitial lung disease (ILD) is unclear. To assess the prognosis of NSCLC
      patients with ILD treated with platinum-based chemotherapy, we retrospectively
      analyzed the clinical course of those with ILD. METHODS: One hundred and four
      NSCLC patients with ILD treated with platinum-based chemotherapy at Shizuoka
      Cancer Center between August 2002 and June 2013 were retrospectively reviewed.
      RESULTS: The combination of carboplatin with paclitaxel was most frequently used
      as the first-line treatment for NSCLC patients with ILD (61 %). The overall
      response rate was 38 % in 104 NSCLC patients with ILD treated with platinum-based
      chemotherapy. In all patients, median progression-free survival and overall
      survival were 4.8 and 9.9 months, respectively. During first-line platinum-based
      chemotherapy, 9 % of the 104 patients with ILD developed chemotherapy-related
      exacerbation of ILD. Multivariate analysis demonstrated that clinical stage was a
      significantly independent prognostic factor (hazard ratio 0.517; 95 % confidence
      interval 0.314-0.842, p = 0.0079). Patients with clinical stage IV or recurrence
      after surgical resection showed poor prognosis (median survival time 8.5 months).
      CONCLUSIONS: Our study suggests that the prognosis of NSCLC patients with ILD is
      poor. The risk of exacerbation of ILD in patients treated with platinum-based
      chemotherapy as the first-line treatment was slightly lower than in previous
      reports.

PMID- 25563719
TI  - A phase II study of biweekly paclitaxel and carboplatin in elderly patients with
      advanced non-small cell lung cancer.
AB  - PURPOSE: The number of elderly patients with advanced non-small cell lung cancer
      (NSCLC) is increasing. Although several studies have suggested the benefit of
      chemotherapy with a platinum doublet for elderly patients with advanced NSCLC,
      this treatment is still controversial in this age group. To evaluate the efficacy
      and tolerability of combination chemotherapy with biweekly paclitaxel and
      carboplatin for elderly patients with advanced NSCLC, we conducted a multicenter,
      non-randomized, open label, phase II trial. METHODS: We recruited patients aged
      >=70 years with clinical stage IIIB and IV NSCLC and ECOG performance status (PS)
      of 0-2. Patients received paclitaxel (90 mg/m(2)) and carboplatin (AUC = 2.5) on
      day 1 and 15, every 4 weeks. The primary endpoint was overall response rate
      (ORR), and the secondary endpoints were progression-free survival (PFS), overall
      survival (OS), and safety. RESULTS: Sixty-five patients (median age 79 years;
      range 70-87 years) were enrolled. Forty-nine patients were men, and 48 were stage
      IV. The PS was 0, 1, and 2 in 28, 33, and 4 patients, respectively. The
      histological type of NSCLC was non-squamous in 69.3 % and squamous cell carcinoma
      in 30.7 % of patients. The median number of treatment cycles was 3 (range 1-6).
      The response rate was 29.4 % (95 % CI 18.7-43.0), and the disease control rate
      was 78.0 % (95 % CI 64.8-87.2). Median PFS and OS were 3.8 months (95 % CI 1.9
      5.3) and 17.3 months (95 % CI 10.4-25.1), respectively. The most common grade 3
      or 4 toxicities were neutropenia (27 %), leukopenia (15 %), infection (10 %), and
      anemia (8 %). CONCLUSION: The combination of biweekly paclitaxel and carboplatin
      was effective and well tolerated in elderly patients with advanced NSCLC.

PMID- 25563721
TI  - Screening for Lynch syndrome: it is time to shift the focus.

PMID- 25563720
TI  - Probability-based interpretation of liver stiffness measurement in untreated
      chronic hepatitis B patients.
AB  - BACKGROUND: Liver stiffness measurement (LSM) by transient elastography is a
      popular noninvasive test of fibrosis. Traditional LSM cutoffs dichotomize
      patients and do not clearly indicate the confidence of diagnosis. AIM: We derived
      and validated probability functions of fibrosis and cirrhosis based on LSM and
      determined the effect of alanine aminotransferase (ALT) on the scores. METHODS:
      Consecutive chronic hepatitis B patients who underwent liver function tests, LSM,
      and liver biopsies at six European and Asian centers (2/3 in the training cohort
      and 1/3 in the validation cohort) were recruited. Binary logistic regression was
      performed to predict the probabilities of different fibrosis stages based on LSM
      and/or ALT. RESULTS: A total of 1,051 patients were included in the final
      analysis (53 % with ALT >= 60 IU/L, 32 % F2, 20 % F3, and 24 % F4). The
      probability functions (LiFA-HBV score) with and without ALT adjustment closely
      mirrored the proportion with different fibrosis stages in both the training and
      validation cohorts. For a range of up to 300 IU/L, ALT maintained a weak linear
      relationship with LSM for each fibrosis stage (r (2) = 0.018-0.13). Based on
      relative integrated discrimination improvement, the addition of ALT to the LiFA
      HBV score increased the correct reclassification of F3-4 and F4 by 5 and 17 %,
      respectively. CONCLUSIONS: ALT increases LSM in a linear fashion in chronic
      hepatitis B patients at any fibrosis stage. The LiFA-HBV score accurately
      predicts the probability of fibrosis. ALT adjustment increases the rate of
      reclassification modestly and is not essential.

PMID- 25563722
TI  - Nesfatin-1 suppresses gastric contractions and inhibits interdigestive migrating
      contractions in conscious dogs.
AB  - BACKGROUND: Nesfatin-1 is a novel 82-amino acid anorectic peptide. Acute
      injection of nesfatin-1 into the third brain ventricle reduces food consumption
      during the dark phase in rats. Nesfatin-1 is also expressed in gastric X/A-like
      cells in the peripheral tissues. Nesfatin-1 has been reported to reduce gastric
      and duodenal motility and to delay gastric emptying. AIM: In the present study,
      we investigated the effects of nesfatin-1 on gastrointestinal motility in
      conscious dogs. METHODS: Force transducers were implanted onto the serosal
      surfaces of the gastric bodies, gastric antra, duodena, and jejuna of healthy
      beagle dogs, and gastrointestinal motility was monitored. We evaluated the
      effects of nesfatin-1 on gastrointestinal motility and on the circulating levels
      of nesfatin-1 in the fasted and fed states. RESULTS: The intravenous
      administration of nesfatin-1 reduced gastric contractions and inhibited cyclical
      interdigestive migrating contractions in the fasted state. In the fasted state,
      circulating levels of nesfatin-1 tended to increase during late phase I. In
      addition, the kinetics of the circulating levels of nesfatin-1 were opposite to
      those of ghrelin during the fasted state. CONCLUSIONS: Nesfatin-1 regulates
      gastrointestinal motility, and, in particular, it inhibits gastric contractions
      in the fasted state. Interdigestive migrating contractions may be regulated by
      interactions between nesfatin-1, ghrelin, and motilin.

PMID- 25563723
TI  - Bone Mineral Density, Bone Turnover, and Systemic Inflammation in Non-cirrhotics
      with Chronic Hepatitis C.
AB  - BACKGROUND: Whether chronic HCV, a disease characterized by systemic
      inflammation, impacts bone mineral density (BMD) independent of cirrhosis is
      unknown. AIM: We aimed to evaluate the association between BMD, systemic
      inflammation, and markers of bone turnover in chronic HCV without cirrhosis.
      METHODS: Non-cirrhotics, 40-60 years old, with chronic HCV underwent measurement
      of: (1) BMD by dual-energy X-ray absorptiometry scan and (2) serum markers of
      systemic inflammation and bone turnover. By Chi-squared or t test, we compared
      those with normal versus low BMD. RESULTS: Of the 60 non-cirrhotics, 53 % were
      female and 53 % Caucasian. Mean (SD) age was 53.3 years (5.7), total bilirubin
      0.7 mg/dL (0.3), creatinine 0.8 mg/dL (0.2), and body mass index 28.4 kg/m(2)
      (6.5). Low BMD was observed in 42 %: 30 % had osteopenia, 12 % had osteoporosis.
      Elevated tumor necrosis factor alpha, interleukin-6, and C-reactive protein
      levels were found in 26, 32, and 5 %, respectively, but did not differ by BMD
      group (p > 0.05). Patients with low BMD had higher serum phosphorus (4.1 vs. 3.5
      mg/dL) and pro-peptide of type 1 collagen (P1NP; 73.1 vs. 47.5 ng/mL) [p < 0.05],
      but similar bone-specific alkaline phosphatase, serum C-telopeptide, and
      parathyroid hormone levels. CONCLUSIONS: Low BMD is prevalent in 40- to 60-year
      old non-cirrhotics with chronic HCV, but not associated with systemic
      inflammatory markers. Elevated P1NP levels may help to identify those at
      increased risk of bone complications in this population. Chronic HCV should be
      considered a risk factor for bone loss, prompting earlier BMD assessments in both
      men and women.

PMID- 25563724
TI  - Diabetes reduces mesenchymal stem cells in fracture healing through a TNFalpha
      mediated mechanism.
AB  - AIMS/HYPOTHESIS: Diabetes interferes with bone formation and impairs fracture
      healing, an important complication in humans and animal models. The aim of this
      study was to examine the impact of diabetes on mesenchymal stem cells (MSCs)
      during fracture repair. METHODS: Fracture of the long bones was induced in a
      streptozotocin-induced type 1 diabetic mouse model with or without insulin or a
      specific TNFalpha inhibitor, pegsunercept. MSCs were detected with cluster
      designation-271 (also known as p75 neurotrophin receptor) or stem cell antigen-1
      (Sca-1) antibodies in areas of new endochondral bone formation in the calluses.
      MSC apoptosis was measured by TUNEL assay and proliferation was measured by Ki67
      antibody. In vitro apoptosis and proliferation were examined in C3H10T1/2 and
      human-bone-marrow-derived MSCs following transfection with FOXO1 small
      interfering (si)RNA. RESULTS: Diabetes significantly increased TNFalpha levels
      and reduced MSC numbers in new bone area. MSC numbers were restored to normal
      levels with insulin or pegsunercept treatment. Inhibition of TNFalpha
      significantly reduced MSC loss by increasing MSC proliferation and decreasing MSC
      apoptosis in diabetic animals, but had no effect on MSCs in normoglycaemic
      animals. In vitro experiments established that TNFalpha alone was sufficient to
      induce apoptosis and inhibit proliferation of MSCs. Furthermore, silencing
      forkhead box protein O1 (FOXO1) prevented TNFalpha-induced MSC apoptosis and
      reduced proliferation by regulating apoptotic and cell cycle genes.
      CONCLUSIONS/INTERPRETATION: Diabetes-enhanced TNFalpha significantly reduced MSC
      numbers in new bone areas during fracture healing. Mechanistically, diabetes
      enhanced TNFalpha reduced MSC proliferation and increased MSC apoptosis. Reducing
      the activity of TNFalpha in vivo may help to preserve endogenous MSCs and
      maximise regenerative potential in diabetic patients.

PMID- 25563725
TI  - SIRT1 activation ameliorates hyperglycaemia by inducing a torpor-like state in an
      obese mouse model of type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Nutrient overabundance and diminished physical activity underlie
      the epidemic of obesity and its consequences of insulin resistance and type 2
      diabetes. These same phenomena, obesity and insulin resistance, are also observed
      in mammals as they ready themselves for the nutrient deprivation of winter, yet
      their plasma glucose does not rise. Given the role of silent information
      regulator 2 (Sir2) and its mammalian orthologue, Sirt1, in survival and life
      extension during energy deprivation, we hypothesised that enhancing its activity
      may reduce the insensible energy loss engendered by hyperglycaemia and
      glycosuria. METHODS: At 8 weeks of age, db/db and db/m mice were randomised to
      receive the SIRT1 activator SRT3025 milled in chow (3.18 g/kg) or regular chow
      and followed for a further 12 weeks. RESULTS: When compared with vehicle, SIRT1
      activation greatly improved glycaemic control, augmented plasma insulin
      concentrations, increased pancreatic islet beta cell mass and elevated hepatic
      expression of the beta cell growth factor, betatrophin in db/db mice. Despite the
      dramatic reduction in hyperglycaemia, db/db mice displayed worsening insulin
      resistance, diminished physical activity and further weight gain. These findings
      along with reduced food intake and reduction in body temperature resembled torpor
      and hibernation. By contrast, SIRT1 activation conferred only minimal changes in
      non-diabetic db/m mice. CONCLUSIONS/INTERPRETATION: While reducing hyperglycaemia
      and promoting beta cell expansion, enhancing the activity of SIRT1 facilitates a
      phenotypic change in a db/db mouse model of diabetes to one that more closely
      resembles the physiological state of torpor or hibernation.

PMID- 25563726
TI  - Shear stress modulates endothelial KLF2 through activation of P2X4.
AB  - Vascular endothelial cells that are in direct contact with blood flow are exposed
      to fluid shear stress and regulate vascular homeostasis. Studies report
      endothelial cells to release ATP in response to shear stress that in turn
      modulates cellular functions via P2 receptors with P2X4 mediating shear stress
      induced calcium signaling and vasodilation. A recent study shows that a loss-of
      function polymorphism in the human P2X4 resulting in a Tyr315>Cys variant is
      associated with increased pulse pressure and impaired endothelial vasodilation.
      Although the importance of shear stress-induced Kruppel-like factor 2 (KLF2)
      expression in atheroprotection is well studied, whether ATP regulates KLF2
      remains unanswered and is the objective of this study. Using an in vitro model,
      we show that in human umbilical vein endothelial cells (HUVECs), apyrase
      decreased shear stress-induced KLF2, KLF4, and NOS3 expression but not that of
      NFE2L2. Exposure of HUVECs either to shear stress or ATPgammaS under static
      conditions increased KLF2 in a P2X4-dependent manner as was evident with both the
      receptor antagonist and siRNA knockdown. Furthermore, transient transfection of
      static cultures of human endothelial cells with the Tyr315>Cys mutant P2X4
      construct blocked ATP-induced KLF2 expression. Also, P2X4 mediated the shear
      stress-induced phosphorylation of extracellular regulated kinase-5, a known
      regulator of KLF2. This study demonstrates a major physiological finding that the
      shear-induced effects on endothelial KLF2 axis are in part dependent on ATP
      release and P2X4, a previously unidentified mechanism. 

PMID- 25563728
TI  - Response to the letter to the editor: Venous oxygen saturation is reduced and
      variable in central retinal vein occlusion.

PMID- 25563727
TI  - Acute central serous chorioretinopathy: a correlation study between fundus
      autofluorescence and spectral-domain OCT.
AB  - PURPOSE: To evaluate the correlation between fundus autofluorescence (FAF) and
      spectral-domain OCT (SD-OCT) morphological analysis in eyes with acute central
      serous chorioretinopathy (CSCR). METHODS: Thirty-one patients with a first
      episode of CSCR and symptom duration of less than 6 weeks were prospectively
      enrolled. FAF and SD-OCT examination were performed at baseline and at 2-month
      intervals. Main outcome measure was the correlation between FAF and SD-OCT
      retinal morphology. RESULTS: At baseline, 30/31 and 29/31 eyes showed a macular
      hypo-AF, corresponding to the neurosensory retinal detachment (SRD), on shortwave
      FAF (SW-FAF) and near-infrared-FAF (NIR-FAF), respectively. While the SRD
      resolved, both FAF techniques showed a granular hyper-AF in 31 eyes. At first
      examination, SD-OCT confirmed the SRD with a photoreceptor outer-segment (OS)
      elongation in all cases. During SRD resolution, the photoreceptor layer appeared
      thicker and fragmented. Multiple hyper-reflective precipitates were detected in
      the outer plexiform and nuclear layer and between the photoreceptors and appeared
      colocalized with the hyper-AF dots composing the granular hyper-AF. After SRD
      resolution, the hypo-AF area reverted to a normal pattern on SW-FAF in all eyes
      and in 25/31 on NIR-FAF. Examination at 12 months showed that the granular hyper
      AF was still detectable in 54 % eyes, whereas 6/31 eyes showed hypo-AF dots on
      NIR-FAF. On SD-OCT, the junction IS/OS was identifiable in 11/31 eyes soon after
      the SRD resolution and appeared completely restored in all patients at the final
      visit. CONCLUSION: The simultaneous acquisition of FAF and SD-OCT provides
      detailed findings of retinal abnormalities of CSCR and may help to understand the
      evolving process linked to CSCR.

PMID- 25563729
TI  - A review of the benefits of Satureja species on metabolic syndrome and their
      possible mechanisms of action.
AB  - Metabolic syndrome, also known as insulin resistance disorder, is the
      simultaneous manifestation of multiple metabolic disorders in an individual. The
      present-day complementary and alternative therapies suggest several medicinal
      herbs that may have the potential to improve one or multiple complications of
      metabolic syndrome. All of them have their own limitations in efficacy and
      unwanted effects. Therefore, we reviewed species of Satureja as widespread
      medicinal herbs and potentially good remedies for metabolic syndrome. We reviewed
      literature found in PubMed and the ISI Web of Knowledge with the key word
      Satureja in the title. The influence of any species of Satureja on any disease or
      syndrome, enzymatic, metabolic, or physiological pathways, in human, animals, or
      in vitro conditions related to any characteristics of metabolic syndrome were
      considered. The main outcomes of treatment with Satureja species were
      categorized, and the possible mechanisms of action are discussed in this article.

PMID- 25563731
TI  - Experimental dog model for assessment of fasting and postprandial fatty acid
      metabolism: pitfalls and feasibility.
AB  - The dog is a widely-used model for conducting metabolic studies. This is mainly
      due to its large size and its physiology which is relatively similar to that of
      humans. Here, we attempted to optimize a postprandial metabolic study protocol
      used in dogs. Following acclimatization, female mongrel dogs underwent 9 h
      profiling for time-course baseline plasma data on triglyceride,
      adrenocorticotropic hormone (ACTH) and cortisol levels. One week later, carotid
      and jugular catheters were surgically inserted for sampling and infusions.
      Initial post-operative care, based on the literature (Protocol 1), consisted of
      analgesia (buprenorphine every 8-12 h and 2-3 doses/day of acepromazine),
      restriction by Pavlov harness within cages, and a two- to three-day recovery
      period. Throughout the experiment, dogs received a lipid tracer diluted in 5%
      bovine serum albumin (BSA). Compared with baseline, animals vomited (n = 6/6) and
      exhibited high ACTH + cortisol levels (stress biomarkers), resulting in blunted
      triglyceride peak levels. To avoid these undesirable effects, post-operative care
      was modified (Protocol 2) as follows: animals (n = 19) were given a single dose
      of buprenorphine and no acepromazine, were unrestrained and free to move within
      cages, the recovery period was extended to seven days, and the lipid tracer was
      diluted in 0.002% versus 5% BSA. Using this modified protocol, postprandial
      plasma-triglyceride and ACTH/cortisol patterns were similar to baseline values.
      Controlling for stressors, as well as for factors which may alter proper
      digestion, is critical for all postprandial metabolic studies. Our results show
      that an optimized postprandial metabolic protocol used in dogs reduces
      experimental variability, while improving animal care and comfort.

PMID- 25563732
TI  - Pathogenesis and management of intradialytic hypertension.
AB  - Hypertension is common in chronic kidney disease patients especially in those
      undergoing hemodialysis (HD). Usually, blood pressure falls after the HD session
      but in some patients a paradoxical increase has been observed during or
      immediately after HD. This phenomenon is referred as intradialytic hypertension.
      HD patients with intradialytic hypertension or increased blood pressure during HD
      present higher cardiovascular (CV) morbidity and mortality rates. The underlying
      mechanism of intradialytic hypertension is multifactorial. Activation both of
      renin-angiotensinaldosterone system (RAAS) and sympathetic nervous system, volume
      and sodium overload with concomitant increase in cardiac output, and endothelial
      dysfunction have been implicated in the pathogenesis of intradialytic
      hypertension. Given the lack of clinical trials regarding the pathophysiology and
      management of intradialytic hypertension, current treatment strategies are based
      mainly on experts' opinion. The purpose of this review is to describe the
      pathophysiology of intradialytic hypertension and discuss current strategies in
      order to improve intradialytic blood pressure management and concomitant HD
      patients' outcomes. 

PMID- 25563730
TI  - Genome-wide methylation analysis in Silver-Russell syndrome patients.
AB  - Silver-Russell syndrome (SRS) is a clinically heterogeneous disorder
      characterised by severe in utero growth restriction and poor postnatal growth,
      body asymmetry, irregular craniofacial features and several additional minor
      malformations. The aetiology of SRS is complex and current evidence strongly
      implicates imprinted genes. Approximately, half of all patients exhibit DNA
      hypomethylation at the H19/IGF2 imprinted domain, and around 10% have maternal
      uniparental disomy of chromosome 7. We measured DNA methylation in 18 SRS
      patients at >485,000 CpG sites using DNA methylation microarrays. Using a novel
      bioinformatics methodology specifically designed to identify subsets of patients
      with a shared epimutation, we analysed methylation changes genome-wide as well as
      at known imprinted regions to identify SRS-associated epimutations. Our analysis
      identifies epimutations at the previously characterised domains of H19/IGF2 and
      at imprinted regions on chromosome 7, providing proof of principle that our
      methodology can detect DNA methylation changes at imprinted loci. In addition, we
      discovered two novel epimutations associated with SRS and located at imprinted
      loci previously linked to relevant mouse and human phenotypes. We identify RB1 as
      an additional imprinted locus associated with SRS, with a region near the RB1
      differentially methylated region hypermethylated in 13/18 (~70%) patients. We
      also report 6/18 (~33%) patients were hypermethylated at a CpG island near the
      ANKRD11 gene. We do not observe consistent co-occurrence of epimutations at
      multiple imprinted loci in single SRS individuals. SRS is clinically
      heterogeneous and the absence of multiple imprinted loci epimutations reflects
      the heterogeneity at the molecular level. Further stratification of SRS patients
      by molecular phenotypes might aid the identification of disease causes.

PMID- 25563733
TI  - One-dimensional manganese-cobalt oxide nanofibres as bi-functional cathode
      catalysts for rechargeable metal-air batteries.
AB  - Rechargeable metal-air batteries are considered a promising energy storage
      solution owing to their high theoretical energy density. The major obstacles to
      realising this technology include the slow kinetics of oxygen reduction and
      evolution on the cathode (air electrode) upon battery discharging and charging,
      respectively. Here, we report non-precious metal oxide catalysts based on spinel
      type manganese-cobalt oxide nanofibres fabricated by an electrospinning
      technique. The spinel oxide nanofibres exhibit high catalytic activity towards
      both oxygen reduction and evolution in an alkaline electrolyte. When incorporated
      as cathode catalysts in Zn-air batteries, the fibrous spinel oxides considerably
      reduce the discharge-charge voltage gaps (improve the round-trip efficiency) in
      comparison to the catalyst-free cathode. Moreover, the nanofibre catalysts remain
      stable over the course of repeated discharge-charge cycling; however, carbon
      corrosion in the catalyst/carbon composite cathode degrades the cycling
      performance of the batteries. 

PMID- 25563735
TI  - The effect of oral magnesium supplementation on serum C-reactive protein.

PMID- 25563734
TI  - A cross-over experiment to investigate possible mechanisms for lower BMIs in
      people who habitually eat breakfast.
AB  - BACKGROUND/OBJECTIVES: The body mass index (BMI) of breakfast eaters is
      frequently reported to be lower compared with that of breakfast skippers. This is
      not explained by differences in energy intakes, indicating there may be other
      mechanisms serving to drive this paradoxical association between breakfast and
      BMI. This study aimed to investigate the effect of eating breakfast versus
      morning fasting on measures predominantly of metabolism in lean and overweight
      participants who habitually eat or skip breakfast. SUBJECTS/METHODS: Participants
      (n=37) were recruited into four groups on the basis of BMI (lean and overweight)
      and breakfast habit (breakfast eater and breakfast skipper). Participants were
      randomly assigned to a breakfast experimental condition, breakfast eating or no
      breakfast, for 7 days and then completed the alternative condition. At the end of
      each breakfast experimental condition, measurements were made before and after a
      high carbohydrate breakfast of 2274 +/- 777 kJ or a rest period. Resting
      metabolic rate, thermic effect of food (TEF), blood glucose, insulin and leptin
      levels were recorded. Hunger and 'morningness' were assessed and pedometers worn.
      RESULTS: Lean participants had lower fasting insulin levels (P=0.045) and higher
      insulin concentrations following breakfast (P=0.001). BMI and breakfast habit did
      not interact with the experimental breakfast condition, with the exception of
      hunger ratings; breakfast eaters were hungrier in the mornings compared with
      breakfast skippers in the no breakfast condition (P=0.001). CONCLUSIONS: There is
      little evidence from this study for a metabolic-based mechanism to explain lower
      BMIs in breakfast eaters.

PMID- 25563736
TI  - Dietary magnesium intake is inversely associated with serum C-reactive protein
      levels: meta-analysis and systematic review.

PMID- 25563738
TI  - Corrigendum. Dietary magnesium intake is inversely associated with serum C
      reactive protein levels: meta-analysis and systematic review.
AB  - Correction to: European Journal of Clinical Nutrition (2014) 68, 510-516;
      doi:10.1038/ejcn.2014.7; published online 12 February 2014 Since the publication
      of this article the authors have noticed an error in the first sentence of the
      last paragraph of the results section. The sentence should be: In addition, five
      Mg intervention studies (Table 2) reported on the association between Mg
      supplementation and serum CRP levels. The authors apologize for any inconvenience
      caused.

PMID- 25563737
TI  - Dietary whey protein influences plasma satiety-related hormones and plasma amino
      acids in normal-weight adult women.
AB  - BACKGROUND/OBJECTIVE: A distinct suppressive effect of a whey protein (including
      glycomacropeptide)-enriched preload drink on subsequent food intake in comparison
      with a maltodextrin carbohydrate-enriched preload was demonstrated in an earlier
      companion study with the same female subjects; however, the potential mediators
      underlying the effect are unclear. The objective of this study was to investigate
      how the ingestion of a whey protein-enriched preload beverage affected
      postprandial plasma concentrations of several satiety-related gastrointestinal
      hormones and metabolites in comparison with a maltodextrin carbohydrate-enriched
      preload. SUBJECTS/METHODS: Eighteen normal-weight women were studied in a single
      blind, randomized block design. Blood samples were collected at various time
      intervals for 120 min after consumption of a test drink (300 ml, ~1300 kJ)
      enriched (45 g) with either maltodextrin carbohydrate or whey protein containing
      naturally present glycomacropeptide. RESULTS: Plasma-active ghrelin
      concentrations decreased after both maltodextrin carbohydrate- and whey protein
      enriched test drinks (P<0.05). The whey protein-enriched beverage led to
      increased plasma concentrations of cholecystokinin (CCK) at 60 and 75 min
      (P<0.05), glucagon-like peptide-1 (GLP-1) at 90 min (P<0.001), peptide tyrosine
      tyrosine (PYY) at 90 and 120 min (P<0.01) and pancreatic polypeptide (PP) from 15
      to 120 min (P<0.05) compared with maltodextrin carbohydrate. Total amino acid,
      urea and ammonia plasma concentrations were also higher after whey protein
      compared with maltodextrin carbohydrate ingestion (P<0.01). CONCLUSIONS:
      Increased plasma concentrations of some gastrointestinal hormones related to
      satiety, particularly PP, and of amino acids and their metabolites, may have
      acted either singly or together to mediate the observed satiety response to whey
      protein.

PMID- 25563740
TI  - Editorial: Recent progress in medicinal natural products drug discovery.

PMID- 25563739
TI  - Functional cobalamin (vitamin B12) deficiency: role of advanced age and disorders
      associated with increased oxidative stress.
AB  - BACKGROUND/OBJECTIVE: Functional cobalamin (Cbl; vitamin B12) deficiency (that
      is, high levels of the Cbl-dependent metabolites, methylmalonic acid (MMA) and
      homocysteine (HCys), despite normal serum Cbl values) is common in the elderly
      and is associated with neurocognitive abnormalities, but its cause is unknown. As
      only reduced Cbls are metabolically active, the possibility that functional Cbl
      deficiency is associated with disorders having biomarkers indicative of increased
      oxidative stress (oxidant risks) was considered. SUBJECTS/METHODS: A
      retrospective record review of community-dwelling adults evaluated over a 12-year
      period for Cbl deficiency in a primary care setting who had serum Cbl values ?400
      pg/ml (n=170). RESULTS: When no oxidant risks were present, older subjects (?70
      years) had higher metabolite values than younger individuals (<70 years). MMA
      values were even higher in the elderly when one oxidant risk was present and in
      younger subjects when two or more oxidant risks were present. Even at Cbl levels
      ?800 pg/ml, MMA values were increased in 73% of elderly subjects with at least
      one oxidant risk. HCys values were also higher in both age groups when at least
      two oxidant risks were present. Cyanocobalamin therapy decreased MMA and HCys
      values in 86 and 76% of subjects, respectively, with nonresponders more likely to
      have two or more oxidant risks. CONCLUSION: Functional Cbl deficiency is
      associated with disorders marked by increased oxidative stress particularly in
      the elderly; it occurs even when Cbl levels are high and is not consistently
      corrected with high-dose cyanocobalamin therapy. Thus, current approaches to
      recognizing and managing this disorder may be inadequate.

PMID- 25563741
TI  - Dynamics of health behaviours and socioeconomic differences in mortality in the
      USA.
AB  - BACKGROUND: To measure the explanatory role of behavioural factors to educational
      and income disparities in mortality among US adults (ages 25+). METHODS: Data
      were from four waves of the American Changing Lives Study (N=3617). There were
      1832 deaths between 1986 and 2011. Smoking, physical activity, alcohol and body
      mass index were examined. RESULTS: Those with 0-11 years of schooling had an 88%
      (95% CI 48% to 139%) increased risk of dying compared to those with 16+years of
      schooling. Behavioural factors explained 41% (95% CI 26% to 55%) and 50% (95% CI
      30% to 70%) of this excess in models that treated behavioural factors as fixed
      (single point in time) and time varying (repeated), respectively. The lowest
      income group (bottom 20th centile) had a 209% (95% CI 172% to 256%) increased
      risk of dying relative to the highest income group (top 40th centile).
      Behavioural factors explained 24% (fixed, 95% CI 13% to 35%) and 39% (repeated,
      95% CI 22% to 56%) of this difference. Analyses of deaths by causes indicated
      that behavioural factors were more consequential to disparities in cardiovascular
      mortality, explaining up to 83% of educational differences, compared to cancer
      and other death causes. CONCLUSIONS: Behavioural factors are one of a number of
      factors which explain socioeconomic mortality disparities, but their estimated
      explanatory role depends on a number of parameters including the socioeconomic
      status measure examined, the cause of death and age. In this nationally
      representative sample, findings based on repeated measures did not warrant a re
      evaluation of earlier estimates.

PMID- 25563742
TI  - Objectively measured physical activity and vitamin D status in older people from
      Germany.
AB  - BACKGROUND: To analyse the seasonal relationship of objectively measured physical
      activity with vitamin D status in older persons from Southern Germany (latitude:
      48.4 degrees N). METHODS: Physical activity was assessed in 1193 community
      dwelling individuals aged >=65 years (58% men) over 1 week using a thigh-worn
      accelerometer. Furthermore, the 25-hydroxyvitamin D (25(OH)D) level was measured.
      Least-square means of 25(OH)D serum levels were calculated for quartiles of
      average daily walking duration stratified by season and adjusted for gender, age
      and body mass index. Participants with prescribed vitamin D supplements were
      excluded. RESULTS: Statistically significant linear associations between
      quartiles of walking duration with 25(OH)D serum levels were observed in all
      seasons but not in summer. Differences in 25(OH)D serum levels between the first
      and the last quartile were 3.42 ng/mL (p=0.002) in winter, 2.80 ng/mL (p=0.009)
      in spring, and 3.60 ng/mL (p<0.001) in the fall. The proportion of vitamin D
      insufficiency (<20 ng/mL) even in the highest quartile of walking duration was
      45.3% in winter, 73.7% in spring, 17.4% in summer and 16.5% in the fall.
      CONCLUSIONS: Although a positive dose-response relationship was seen between
      walking duration and the 25(OH)D serum level for most seasons, vitamin D
      insufficiency was still very prevalent even in high-active persons during all
      seasons.

PMID- 25563743
TI  - A novel ecological methodology for constructing ethnic-majority life tables in
      the absence of individual ethnicity information.
AB  - BACKGROUND: Deprivation-specific life tables have been in use for some time, but
      health outcomes are also known to vary by ethnicity over and above deprivation.
      The mortality experiences of ethnic groups are little studied in the UK, however,
      because ethnicity is not captured on death certificates. METHODS: Population data
      for all Output Areas (OAs) in England and Wales were stratified by age-group, sex
      and ethnic proportion, and matched to the deaths counts in that OA from 2000 to
      2002. We modelled the relationship between mortality, age, deprivation and ethnic
      proportion. We predicted mortality rates for an area that contained the maximum
      proportion of each ethnic group reported in any area in England and Wales, using
      a generalised linear model with a Poisson distribution adjusted for deprivation.
      RESULTS: After adjustment, Asian and White life expectancies between 1 and 80
      years were very similar. Black men and women had lower life expectancies: men by
      4 years and women by around 1.5 years. The Asian population had the lowest
      mortality of all groups over age 45 in women and over 50 in men, whereas the
      Black population had the highest rates throughout, except in girls under 15.
      CONCLUSIONS: We adopted a novel ecological method of constructing ethnic-majority
      life tables, adjusted for deprivation. There is still diversity within these
      three broad ethnic groups, but our data show important residual differences in
      mortality for Black men and women. These ethnic life tables can be used to inform
      public health planning and correctly account for background mortality in ethnic
      subgroups of the population.

PMID- 25563745
TI  - Does falling testosterone with age among men underlie the increase in ischaemic
      heart disease.
AB  - BACKGROUND: Observationally, testosterone falls with age among men and ischaemic
      heart disease (IHD) increases with age, so testosterone is commonly assumed to
      protect against IHD. Here we examined whether IHD mortality rates among men
      increased faster with age in the USA than China, where testosterone in men
      remains stable throughout adulthood, and also whether the increase with age in
      mortality rates for IHD is faster than for other causes of death. METHODS: Age
      specific mortality rates from all causes, IHD, pneumonia and prostate cancer for
      men in the USA and China from 1991 to 1995 were obtained from the WHO, and
      considered in age groups because of non-linearity. RESULTS: The risk of death
      from IHD in US men increased with age at the same rate as the risk of death from
      any cause. In China, the risk of death from IHD increased with age faster than
      the risk of death from any cause. CONCLUSION: The data are not consistent with
      the assumption that a fall in testosterone with age causes IHD.

PMID- 25563746
TI  - Factors affecting toxicity test endpoints in sensitive life stages of native Gulf
      of Mexico species.
AB  - Indigenous species are less commonly used in laboratory aquatic toxicity tests
      compared with standard test species due to (1) limited availability lack of
      requisite information necessary for their acclimation and maintenance under
      laboratory conditions and (2) lack of information on their sensitivity and the
      reproducibility of toxicity test results. As part of the Natural Resource Damage
      Assessment aquatic toxicity program in response to the Deepwater Horizon Oil
      incident (2010), sensitive life stages of native Gulf of Mexico species were
      evaluated in laboratory toxicity tests to determine the potential effects of the
      spill. Fish (n = 5) and invertebrates (n = 2) selected for this program include
      the following: the Florida pompano (Trachinotus carolinus), red drum (Sciaenops
      ocellatus), spotted sea trout (Cynoscion nebulosus), cobia (Rachycentron
      canadum), red porgy (Pagrus pagrus), blue crab (Callinectes sapidus), and the
      common moon jellyfish (Aurelia aurita). Initially in the program, to establish
      part of the background information, acute tests with reference toxicants (CdCl2,
      KCl, CuSO4) were performed with each species to establish data on intraspecies
      variability and test precision as well as identify other factors that may affect
      toxicity results. Median lethal concentration (LC50) values were calculated for
      each acute toxicity test with average LC50 values ranging from 248 to 862 mg/L
      for fish exposures to potassium chloride. Variability between test results was
      determined for each species by calculating the coefficient of variation (%CV)
      based on LC50 values. CVs ranged from 11.2 % for pompano (96-h LC50 value) to
      74.8 % for red porgy 24-h tests. Cadmium chloride acute toxicity tests with the
      jellyfish A. aurita had the lowest overall CV of 3.6 %. By understanding acute
      toxicity to these native organisms from a compound with known toxicity ranges and
      the variability in test results, acute tests with nonstandard species can be
      better interpreted and used appropriately when determining risk.

PMID- 25563744
TI  - Smoking, sex, risk factors and abdominal aortic aneurysms: a prospective study of
      18 782 persons aged above 65 years in the Southern Community Cohort Study.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is a leading cause of death in the
      USA. We evaluated the incidence and predictors of AAA in a prospectively followed
      cohort. METHODS: We calculated age-adjusted AAA incidence rates (IR) among 18 782
      participants aged >=65 years in the Southern Community Cohort Study who received
      Medicare coverage from 1999-2012, and assessed predictors of AAA using
      multivariable Cox proportional hazards models, overall and stratified by sex,
      adjusting for demographic, lifestyle, socioeconomic, medical and other factors.
      HRs and 95% CIs were calculated for AAA in relation to factors ascertained at
      enrolment. RESULTS: Over a median follow-up of 4.94 years, 281 cases were
      identified. Annual IR was 153/100,000, 401, 354 and 174 among blacks, whites, men
      and women, respectively. AAA risk was lower among women (HR 0.48, 95% CI 0.36 to
      0.65) and blacks (HR 0.51, 95% CI 0.37 to 0.69). Smoking was the strongest risk
      factor (former: HR 1.91, 95% CI 1.27 to 2.87; current: HR 5.55, 95% CI 3.67 to
      8.40), and pronounced in women (former: HR 3.4, 95% CI 1.83 to 6.31; current: HR
      9.17, 95% CI 4.95 to 17). A history of hypertension (HR 1.44, 95% CI 1.04 to
      2.01) and myocardial infarction or coronary artery bypass surgery (HR 1.9, 95% CI
      1.37 to 2.63) was negatively associated, whereas a body mass index >=25 kg/m(2)
      (HR 0.72; 95% CI 0.53 to 0.98) was protective. College education (HR 0.6, 95% CI
      0.37 to 0.97) and black race (HR 0.44, 95% CI 0.28 to 0.67) were protective among
      men. CONCLUSIONS: Smoking is a major risk factor for incident AAA, with a strong
      and similar association between men and women. Further studies are needed to
      evaluate benefits of ultrasound screening for AAA among women smokers.

PMID- 25563747
TI  - New insights into lung development and diseases: the role of microRNAs.
AB  - MicroRNAs (miRNAs) are short endogenous noncoding RNA molecules (~ 22
      nucleotides) that can regulate gene expression at the post-transcription level.
      Research interest in the role of miRNAs in lung biology is emerging. MiRNAs have
      been implicated in a range of processes such as development, homeostasis, and
      inflammatory diseases in lung tissues and are capable of inducing
      differentiation, morphogenesis, and apoptosis. In recent years, several studies
      have reported that miRNAs are differentially regulated in lung development and
      lung diseases in response to epigenetic changes, providing new insights for their
      versatile role in various physiological and pathological processes in the lung.
      In this review, we discuss the contribution of miRNAs to lung development and
      diseases and possible future implications in the field of lung biology.

PMID- 25563750
TI  - alpha-Tocopherol derived lipid dimers as efficient gene transfection agents.
      Mechanistic insights into lipoplex internalization and therapeutic induction of
      apoptotic activity.
AB  - In this report, we present cationic dimeric (gemini) lipids for significant
      plasmid DNA (pDNA) delivery to different cell lines without any marked toxicity
      in the presence of serum. Six gemini lipids based on alpha-tocopherol were
      synthesized, which differed in their spacer chain lengths. Each of these gemini
      lipids mixed with a helper lipid, 1,2-dioleoyl phosphatidyl ethanolamine (DOPE),
      was capable of forming stable aqueous suspensions. These co-liposomal systems
      were examined for their potential to transfect pEGFP-C3 plasmid DNA into nine
      cell lines of different origins. The transfection efficacies noticed in terms of
      EGFP expression levels using flow cytometry were well corroborated using
      independent fluorescence microscopy studies. Significant EGFP expression levels
      were reported using the gemini co-liposomes, which counted significantly better
      than one well known commercial formulation, Lipofectamine 2000 (L2 K).
      Transfection efficacies were also analyzed in terms of the degree of
      intracellular delivery of labeled plasmid DNA (pDNA) using confocal microscopy,
      which revealed an efficient internalization in the presence of serum. The cell
      viability assays performed using optimized formulations demonstrated no
      significant toxicity towards any of the cell lines used in the study. We also had
      a look at the lipoplex internalization pathway to profile the uptake
      characteristics. A caveolae/lipid raft route was attributed to their excellent
      gene transfection capabilities. The study was further advanced by using a
      therapeutic p53-EGFP-C3 plasmid and the apoptotic activity was observed using
      FACS and growth inhibition assay. 

PMID- 25563749
TI  - Oxytocin receptor gene methylation: converging multilevel evidence for a role in
      social anxiety.
AB  - Social anxiety disorder (SAD) is a commonly occurring and highly disabling
      disorder. The neuropeptide oxytocin and its receptor (OXTR) have been implicated
      in social cognition and behavior. This study-for the first time applying a
      multilevel epigenetic approach-investigates the role of OXTR gene methylation in
      categorical, dimensional, and intermediate neuroendocrinological/neural network
      phenotypes of social anxiety. A total of 110 unmedicated patients with SAD and
      matched 110 controls were analyzed for OXTR methylation by direct sequencing of
      sodium bisulfite-converted DNA extracted from whole blood. Furthermore, OXTR
      methylation was investigated regarding SAD-related traits (Social Phobia Scale
      (SPS) and Social Interaction Anxiety Scale (SIAS)), salivary cortisol response
      during the Trier social stress test (TSST), and amygdala responsiveness to social
      phobia related verbal stimuli using fMRI. Significantly decreased OXTR
      methylation particularly at CpG Chr3: 8 809 437 was associated with (1) the
      categorical phenotype of SAD (p<0.001, Cohen's d=0.535), (2) increased SPS and
      SIAS scores (p<0.001), (3) increased cortisol response to the TSST (p=0.02), and
      (4) increased amygdala responsiveness during social phobia-related word
      processing (right: p(corr)<0.001; left: p(corr)=0.005). Assuming that decreased
      OXTR methylation confers increased OXTR expression, the present finding may
      reflect a compensatory upregulation for pathologically reduced oxytocin levels or
      a causally relevant increased OXTR activation in SAD and related traits. OXTR
      methylation patterns might thus serve as peripheral surrogates of oxytocin tone
      and aid in establishing accessible biomarkers of SAD risk allowing for indicated
      preventive interventions and personalized treatment approaches targeting the
      oxytocin system.

PMID- 25563748
TI  - Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with
      Working Memory Processing and Response to Treatment with Antipsychotics.
AB  - Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal
      cortical physiology and response to treatment with antipsychotics in
      schizophrenia. Similarly, functional variation in the genes encoding these
      receptors is also associated with these phenotypes. In particular, the DRD2
      rs1076560 T allele predicts a lower ratio of expression of D2 short/long
      isoforms, suboptimal working memory processing, and better response to
      antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T
      allele is associated with lower 5-HT2A expression, impaired working memory
      processing, and poorer response to antipsychotics compared with the C allele.
      Here, we investigated in healthy subjects whether these functional polymorphisms
      have a combined effect on prefrontal cortical physiology and related cognitive
      behavior linked to schizophrenia as well as on response to treatment with second
      generation antipsychotics in patients with schizophrenia. In a total sample of
      620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T
      alleles have greater fMRI prefrontal activity during working memory. Similar
      results were obtained within the attentional domain. Also, the concomitant
      presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral
      accuracy during working memory. Moreover, we found that rs1076560 T
      carrier/rs6314 CC individuals had better responses to antipsychotic treatment in
      two independent samples of patients with schizophrenia (n=63 and n=54,
      respectively), consistent with the previously reported separate effects of these
      genotypes. These results indicate that DRD2 and HTR2A genetic variants together
      modulate physiological prefrontal efficiency during working memory and also
      modulate the response to antipsychotics. Therefore, these results suggest that
      further exploration is needed to better understand the clinical consequences of
      these genotype-phenotype relationships. 

PMID- 25563753
TI  - Synthesis, structure, and properties of a dialumane supported by pyrazolate
      ligands.
AB  - The dialumane [Al2][Na(Ph2pz)3]2 () has been prepared by the reaction of
      Na(Ph2pz) with a metastable solution of AlCl. The structure of contains two
      hydrotris(pyrazolyl)borate-like Na(Ph2pz)3(2-) moieties that are coordinated to
      each Al atom of the dialumane in a kappa(2),kappa(1)-N,N,N fashion and several pi
      stacking interactions are present between the pyrazolate and phenyl rings. In
      solution the pyrazolate ligands in are in dynamic exchange, even at -80  degrees
      C, which shows the lability of these ligands to the low-valent aluminum centers. 

PMID- 25563752
TI  - One-step synthesis of magnetic hollow mesoporous silica (MHMS) nanospheres for
      drug delivery nanosystems via electrostatic self-assembly templated approach.
AB  - In this work, yolk-shell structured magnetic hollow mesoporous silica (MHMS)
      nanospheres with controllable magnetic responsibility, high specific surface
      area, a huge cavity and ink-bottle type mesopores were successfully synthesized
      in one-step by an electrostatic self-assembly templated approach. The obtained
      MHMS nanospheres exhibited low cytotoxicity, excellent biocompatibility and
      potential application in the biomedical field. 

PMID- 25563751
TI  - Leader cells regulate collective cell migration via Rac activation in the
      downstream signaling of integrin beta1 and PI3K.
AB  - Collective cell migration plays a crucial role in several biological processes,
      such as embryonic development, wound healing, and cancer metastasis. Here, we
      focused on collectively migrating Madin-Darby Canine Kidney (MDCK) epithelial
      cells that follow a leader cell on a collagen gel to clarify the mechanism of
      collective cell migration. First, we removed a leader cell from the migrating
      collective with a micromanipulator. This then caused disruption of the cohesive
      migration of cells that followed in movement, called "follower" cells, which
      showed the importance of leader cells. Next, we observed localization of active
      Rac, integrin beta1, and PI3K. These molecules were clearly localized in the
      leading edge of leader cells, but not in follower cells. Live cell imaging using
      active Rac and active PI3K indicators was performed to elucidate the relationship
      between Rac, integrin beta1, and PI3K. Finally, we demonstrated that the
      inhibition of these molecules resulted in the disruption of collective migration.
      Our findings not only demonstrated the significance of a leader cell in
      collective cell migration, but also showed that Rac, integrin beta1, and PI3K are
      upregulated in leader cells and drive collective cell migration. 

PMID- 25563754
TI  - Curative Resection Following Neoadjuvant Chemotherapy for Advanced Gastric Cancer
      With Preservation of a Right Gastroepiploic Artery Coronary Artery Bypass Graft:
      A Case Report.
AB  - Recently, the right gastroepiploic artery (RGEA) has been used in coronary artery
      bypass graft (CABG) as an alternative arterial graft. Because of the improvement
      of prognosis after CABG, malignant diseases are more common in older patients.
      However, there is a serious problem in patients with gastric cancer after CABG
      with RGEA graft. In these patients, an interruption of coronary blood supply
      through the RGEA may cause a life-threatening myocardial ischemia. Therefore, an
      appropriate strategy is very important to avoid risk while retaining the
      curability of the operation. We herein describe a 76-year-old Japanese man with
      advanced gastric cancer who underwent CABG using the RGEA. Abdominal computed
      tomography (CT) showed #6 lymph nodes (sub-pyloric lymph nodes) metastases
      surrounding the RGEA. We concluded that curative resection was impossible while
      preserving the RGEA and started combination chemotherapy using S-1 and cisplatin.
      After 2 courses of that, #6 lymph nodes were reduced extremely. Thereafter the
      patient underwent distal gastrectomy with regional lymph node dissection around
      the RGEA without excision of the RGEA. Histologically, there were no metastases
      in #6 lymph nodes. Neoadjuvant chemotherapy may be effective for preserving the
      RGEA graft in a patient with advanced gastric cancer after CABG. 

PMID- 25563755
TI  - Gonadotropin-releasing hormone and gonadal steroids regulate transcription factor
      mRNA expression in primary pituitary and immortalized gonadotrope cells.
AB  - Hormonal regulation of pituitary gonadotropin gene expression has been attributed
      to gonadotropin-releasing hormone (GnRH)-mediated stimulation of immediate early
      gene expression and gonadal steroid interactions with their respective nuclear
      receptors. A number of orphan nuclear receptors including steroidogenic factor 1,
      liver receptor homologue 1, dosage-sensitive sex reversal, adrenal hypoplasia
      critical region, on chromosome X, gene 1, and chicken ovalbumin upstream promoter
      transcription factors I/II as well as the GATA family members, GATA2 and GATA4,
      have also been implicated in transcriptional regulation of the gonadotropin
      genes. We hypothesized that hormonally mediated changes in these latter
      transcription factors may provide an additional mechanism for mediating hormonal
      effects beyond the more classically appreciated pathways. In these studies, we
      demonstrate significant regulation of orphan nuclear receptor and GATA messenger
      RNA levels by GnRH, dihydrotestosterone, estradiol, and progesterone in both
      cultured primary pituitary cells and gonadotrope-derived cell line, LbetaT2.
      These results advance our understanding of the complex mechanisms by which GnRH
      and steroid hormones achieve precise regulation of anterior pituitary function. 

PMID- 25563756
TI  - Transplacental Distribution of Lidocaine and Its Metabolite in Peridural
      Anesthesia Administered to Patients With Gestational Diabetes Mellitus.
AB  - BACKGROUND: Neonatal effects of drugs administered to mothers before delivery
      depend on the quantity that crosses the placental barrier, which is determined by
      the pharmacokinetics of the drug in the mother, fetus, and placenta. Diabetes
      mellitus can alter the kinetic disposition and the metabolism of drugs. This
      study investigated the placental transfer of lidocaine and its metabolite
      monoethylglycinexylidide (MEGX) in pregnant women with gestational diabetes
      mellitus (GDM) submitted to peridural anesthesia. PATIENTS AND METHODS: A total
      of 10 normal pregnant women (group 1) and 6 pregnant women with GDM (group 2)
      were studied, all at term. The patients received 200 mg 2% lidocaine
      hydrochloride by the peridural locoregional route. Maternal blood samples were
      collected at the time of delivery and, after placental expulsion, blood samples
      were collected from the intervillous space, umbilical artery, and vein for
      determination of lidocaine and MEGX concentrations and analysis of the placental
      transfer of the drug. RESULTS: The following respective lidocaine ratios between
      the maternal and the fetal compartments were obtained for groups 1 and 2:
      umbilical vein/maternal peripheral blood, 0.60 and 0.46; intervillous
      space/maternal blood, 1.01 and 0.88; umbilical artery/umbilical vein, 0.77 and
      0.91; and umbilical vein/intervillous space, 0.53 and 0.51. The following MEGX
      ratios for groups 1 and 2 were, respectively, fetal/maternal, 0.43 and 0.97;
      intervillous space/maternal blood, 0.64 and 0.90; umbilical artery/umbilical
      vein, 1.09 and 0.99; and umbilical vein/intervillous space, 0.55 and 0.78.
      CONCLUSION: Gestational diabetes mellitus did not affect the transplacental
      transfer of lidocaine but interfered with the transfer of MEGX, acting as a
      mechanism facilitating the transport of the metabolite.

PMID- 25563757
TI  - The relationship between amount of soda consumed and intention to reduce soda
      consumption among adults exposed to the Choose Health LA 'Sugar Pack' health
      marketing campaign.
AB  - OBJECTIVE: To examine behavioural intention to reduce soda consumption after
      exposure to the Choose Health LA 'Sugar Pack' campaign in Los Angeles County,
      California, USA. DESIGN: A cross-sectional street-intercept survey was conducted
      to assess knowledge, attitudes, health behaviours and behavioural intentions
      after exposure to the 'Sugar Pack' campaign. A multivariable regression analysis
      was performed to examine the relationships between the amount of soda consumed
      and self-reported intention to reduce consumption of non-diet soda among adults
      who saw the campaign. SETTING: Three pre-selected Los Angeles County Metro bus
      shelters and/or rail stops with the highest number of 'Sugar Pack' campaign
      advertisement placements. SUBJECTS: Riders of the region's Metro buses and
      railways who were the intended audience of the campaign advertisements. RESULTS:
      The overall survey response rate was 56 % (resulting n 1041). Almost 60 % of
      respondents were exposed to the advertisements (619/1041). The multivariable
      logistic regression analysis suggested that the odds of reporting intention to
      reduce soda consumption among moderate consumers (1-6 sodas/week) were 1.95 times
      greater than among heavy consumers (>=1 soda/d), after controlling for clustering
      and covariates. Respondents with less than a high-school education and who
      perceived sugary beverage consumption as harmful also had higher odds; in
      contrast, respondents aged >=65 years had lower odds. CONCLUSIONS: Results
      suggest that future campaigns should be tailored differently for moderate v.
      heavy consumers of soda. Similar tailoring strategies are likely needed for
      younger groups, for those with less educational attainment and for those who do
      not perceive consumption of soda as harmful.

PMID- 25563758
TI  - Handling of medical knowledge in sport: Athletes' medical opinions, information
      seeking behaviours and knowledge sources.
AB  - Medical care in sport comprises a variety of treatments, from scientifically
      proven biomedicine to complementary and alternative medicine. Information and
      knowledge about these diverse treatment options is spread by different sources.
      Thus, athletes encounter information of varying content, quality and background.
      This exploratory pilot study addresses athletes' medical opinions, their health
      related information seeking behaviour and the knowledge sources they utilise.
      Questionnaires were used to examine n = 110 German athletes (n(male) = 69,
      n(female) = 41; mean(age) = 24.28 +/- 4.97 years) at high performance levels
      (national team and/or European championship and/or World championship n = 22;
      first national league and/or German championship n = 51, second national league
      and/or State championship n = 37) from various Olympic sports. A cluster analysis
      regarding the athletes' attitudes towards sport medicine exhibited four different
      types of athletes: 'the autonomous athlete', 'the open-minded athlete', 'the
      functionalistic athlete' and 'the conservative athlete'. In general, our findings
      show that the most used and trusted information sources are physicians and
      physiotherapists. However, medical information is trusted the most if it is
      experience- and field-tested, and comes from the athletes' sport-specific
      network. Our findings also suggest that professional medical knowledge management
      in competitive sport is needed.

PMID- 25563759
TI  - [Isokinetic assessment of ankles in patients with rheumatoid arthritis].
AB  - INTRODUCTION: The foot and ankle in rheumatoid arthritis undergo highly
      destructive synovitis with loss of muscle strength. OBJECTIVE: To evaluate the
      muscle strength of ankles in patients with rheumatoid arthritis based on
      isokinetic dynamometry parameters. MATERIAL AND METHODS: Thirty patients with a
      diagnosis of rheumatoid arthritis involving the ankle(s) and 30 healthy subjects
      (control group) matched for age, gender, race, body mass index and lower limb
      dominance were studied. Dorsiflexion, plantarflexion, inversion and eversion were
      evaluated in all subjects on an isokinetic Cybex Norm dynamometer. The variables
      were compared between the rheumatoid arthritis and control groups and between the
      right and left ankles, and the dorsiflexor/plantar flexor and invertor/evertor
      muscle strength ratio was determined. RESULTS: Patients with rheumatoid arthritis
      performed statistically worse in the isokinetic dynamometry test for all ankle
      movements. The muscle strength ratio between dorsiflexors and plantar flexors was
      different in the two groups. No significant differences were observed in the
      invertor and evertor ratios. In the two groups the plantar flexor musculature was
      statistically stronger than dorsiflexors. CONCLUSION: We conclude that patients
      with rheumatoid arthritis perform worse in isokinetic dynamometry regarding all
      ankle movements than control subjects, with similar isokinetic test results being
      observed for the right and left side in both groups, with few exceptions.
      Isokinetic evaluation posed no additional risk such as important pain or
      inflammatory activity to patients with rheumatoid arthritis.

PMID- 25563760
TI  - [Two pairs of brothers with juvenile idiopathic arthritis (JIA): case reports].
AB  - This is a case report of juvenile idiopathic arthritis (JIA) in two pairs of
      brothers followed in the department of pediatric rheumatology, Universidade
      Federal da Bahia. Genetic involvement in JIA pathogenesis is clear and the risk
      of recurrence among siblings supports this contribution. An important landmark of
      this discovery involves the acknowledgment of major histocompatibility complex
      (MHC) polymorphism contribution to JIA development susceptibility. Despite many
      advances, the numerous available studies cannot explain several implicit
      mechanisms in JIA pathogenesis yet. 

PMID- 25563761
TI  - Prevention of allergic conjunctivitis in mice by a rice-based edible vaccine
      containing modified Japanese cedar pollen allergens.
AB  - BACKGROUND/AIMS: To determine whether oral immunotherapy with transgenic rice
      seeds expressing hypoallergenic modified antigens suppresses cedar pollen-induced
      allergic conjunctivitis by eliciting immune tolerance in mice. METHODS: BALB/c
      mice were fed once a day for 20 days with 220 mg of transgenic rice expressing
      modified Japanese cedar pollen allergens Cry j 1 and Cry j 2 or with non
      transgenic rice seeds as a control. They were then sensitised with two
      intraperitoneal injections of Japanese cedar pollen in alum before challenge
      twice with pollen in eye drops. Twenty-four hours after the second challenge, the
      conjunctiva, spleen, and blood were isolated for histological analysis, cytokine
      production assays, and measurement of serum immunoglobulin E concentrations,
      respectively. RESULTS: The numbers of eosinophils and total inflammatory cells in
      the conjunctiva were significantly lower in mice fed the transgenic rice than in
      those fed non-transgenic rice. The clinical score evaluated at 15 min after
      antigen challenge was also significantly lower in mice fed the transgenic rice
      than in those fed non-transgenic rice. The serum concentrations of both total and
      allergen-specific immunoglobulin E were also significantly lower in mice fed the
      transgenic rice. Oral vaccination with transgenic rice resulted in significant
      down-regulation of the allergen-induced production of interleukin (IL)-2, IL-4,
      IL-5, IL-12p70, interferon-gamma, and IL-17A by splenocytes. CONCLUSIONS: Oral
      immunotherapy with transgenic rice expressing modified Japanese cedar pollen
      allergens suppressed pollen-induced experimental allergic conjunctivitis in mice
      by eliciting immune tolerance. This novel prophylactic approach is potentially
      safe and effective for allergen-specific oral immunotherapy in allergic
      conjunctivitis.

PMID- 25563762
TI  - Modified lamellar keratoplasty and immunosuppressive therapy guided by in vivo
      confocal microscopy for perforated Mooren's ulcer.
AB  - AIM: To observe the efficacy of modified lamellar keratoplasty (LK) and
      immunosuppressive therapy guided by in vivo confocal microscopy (IVCM) for
      perforated Mooren's ulcer. METHODS: 25 patients (31 eyes) with perforated
      Mooren's ulcer underwent modified LK. The perforated hole was patched with a
      thin, fresh posterior cornea containing the endothelium, before a glycerin
      preserved lamellar graft shaped like the defect was placed. Immunosuppressants
      and corticosteroids were used and their dosages adjusted following the density of
      dendritic cells in the corneal graft postoperatively as detected by IVCM. The
      anatomical recovery, visual acuity, surgical complications, and recurrence were
      followed up for 24 months. RESULTS: Favourable anatomical recovery was achieved
      in 27 eyes (87.1%). The vision was significantly improved in all eyes (p<0.05).
      Four eyes (12.9%) had leakage at the graft-host interface. No allograft autolysis
      or immunological rejection was observed. A large number of dendritic cells
      existed in the peripheral and central graft at 1 week postoperatively, with a
      mean density of 359.47+/-97.21 cells/mm(2) and 216.93+/-57.86 cells/mm(2),
      respectively, which significantly decreased to 93.83+/-31.07 cells/mm(2) and
      43.65+/-28.43 cells/mm(2) at 2 months. Accordingly, the dosage of medication was
      gradually reduced during this period. At 6 months, if no dendritic cells were
      found in the graft, use of the topical drug was stopped. The disease recurrence
      rate was 9.7%. CONCLUSIONS: Modified LK, combined with immunosuppressive therapy,
      can effectively treat perforated Mooren's ulcer, with few complications. The use
      of corticosteroids and immunosuppressants guided by IVCM may reduce the disease
      recurrence.

PMID- 25563763
TI  - Quantitative comparison of macular segmentation performance using identical
      retinal regions across multiple spectral-domain optical coherence tomography
      instruments.
AB  - PURPOSE: Comparison of optical coherence tomography (OCT) segmentation
      performance regarding technical accuracy and clinical relevance. METHODS: 29 eyes
      were imaged prospectively with Spectralis (Sp), Cirrus (Ci), 3D-OCT 2000 (3D) and
      RS-3000 (RS) OCTs. Raw data were evaluated in validated custom software. A 1 mm
      diameter subfield, centred on the fovea, was investigated to compare identical
      regions for each case. Segmentation errors were corrected on each B-scan enclosed
      in this subfield. Proportions of wrongly segmented A-scans were noted for inner
      and outer retinal boundaries. Centre point thickness (CPT) and central macular
      thickness (CMT) were compared before and after correction. RESULTS: Segmentation
      errors occurred in 77% and affected on average 29% of A-scans, resulting in mean
      differences of 24/13 um (CPT/CMT). The incidence of segmentation errors was 48%
      (Sp), 79% (Ci), 86% (3D) and 93% (RS), p<0.001. Mean proportions of A-scans with
      wrong outer retinal boundary were 30% (Sp), 9% (Ci), 23% (3D) and 10% (RS),
      p=0.006; proportions for the inner retinal boundary were 11% (Sp), 12% (Ci), 6%
      (3D) and 21% (RS), p=0.034. Mean deviations in CPT/CMT were 41/28 um (Sp), 17/11
      um (Ci), 30/13 um (3D) and 18/8 um (RS), p=0.409/0.477. CONCLUSIONS: By
      comparison of identical regions, substantial differences were detected between
      the tested OCT devices regarding technical accuracy and clinical impact.
      Spectralis showed lowest error incidence but highest error impact.

PMID- 25563764
TI  - Ophthalmic grading of facial paralysis: need for a closer look.
AB  - Very many variations of facial grading systems have been developed, but none
      address the ophthalmic complications of facial nerve weakness adequately. The
      important priorities for ophthalmic surgeon are protecting the ocular surface,
      maintaining sight and peripheral vision, as well as improving the cosmesis of
      periocular area. The absence of a universally agreed grading system on the
      ophthalmic plastic complications of facial nerve paralysis is an obstacle to
      standardised treatment. It is time for clinicians to recognise this need. 

PMID- 25563765
TI  - Efficacy and safety of pre-Descemet's membrane sutures for the management of
      acute corneal hydrops in keratoconus.
AB  - AIMS: The aim of this study was to assess the efficacy and safety of pre
      Descemet's membrane (DM) sutures associated with intracameral air injection for
      management of acute corneal hydrops associated with keratoconus. METHODS: We
      carried out a retrospective interventional study of seven consecutive cases.
      Three to seven pre-DM sutures with 10-0 nylon were applied perpendicularly to the
      tear as close as possible to DM, under general anaesthesia. An air bubble was
      injected into the anterior chamber at the end of each procedure. RESULTS: Corneal
      oedema began to decrease from day 1 after surgery in all our patients. Best
      corrected visual acuity progressed from 2.13 to 1.65 logMar (p=0.031) 1 month
      after surgery, and from 2.13 to 0.84 logMar (p=0.016) 2 months after surgery. The
      mean corneal thickness measured by anterior segment optical coherence tomography
      decreased from 1472 um (range 689-2770 um) on day 0 to 909 um (range 484-1640 um)
      on day 1 (p=0.016), 716 um (range 484-1380 um) on day 15 (p=0.016) and 528 um
      (range 404-618 um) 1 month after surgery. CONCLUSIONS: Our results suggest that
      intrastromal pre-DM sutures and intracameral air injection could promptly restore
      imperviousness of posterior stroma. This technique seems to be a safe and useful
      procedure to shorten acute corneal hydrops.

PMID- 25563768
TI  - The ligand effect on the isomer stability of Au24(SR)20 clusters.
AB  - A key challenge in nanocluster research in particular and nanoscience in general
      is structure prediction for known compositions. Usually a simple ligand such as a
      methyl group is used to replace complex ligands in structure prediction of ligand
      protected nanoclusters. However, how ligands dictate the energy landscape of such
      a cluster remains unclear. Here we elucidate the role of the ligand effect on the
      isomer stability of Au24(SR)20 nanoclusters by computing the relative energy of
      two isomers (one from the experiment, denoted as the "J" isomer; the other is the
      best theoretical model, denoted as the "P" isomer) of Au24(SR)20 with dispersion
      corrected density functional theory. We find that when R = -CH3, the two isomers
      are equally stable (within 0.13 eV), but for R = -CH2CH2Ph the P isomer is more
      stable by 1.6 eV and for R = -CH2Ph-(t)Bu the J isomer is more stable by 1.0 eV.
      Partition of the total energy into DFT and vdW contributions indicates that the
      higher stability of the P isomer in the case of R = -CH2CH2Ph stems from the
      stronger vdW interactions among -CH2CH2Ph groups, while the higher stability of
      the J isomer in the case of R = -CH2Ph-(t)Bu is due to its better capacity to
      respond to the steric effect of the larger -CH2Ph-(t)Bu groups. This finding
      confirms that the ligand plays a crucial role in dictating the isomer stability. 

PMID- 25563766
TI  - Migration study of lens opacities in Bangladeshi adults in London and Bangladesh:
      a pilot study.
AB  - BACKGROUND: Lens opacities (LO) occur at an earlier age and have a higher
      prevalence in developing countries. In this pilot study, we assessed the
      feasibility and practical challenges of conducting a migration study, testing the
      hypothesis that migration from Bangladesh to the UK decreases the amount of LO on
      account of less exposure to adverse environmental factors. METHODS: The sample,
      which was selected from East London, UK and in Bangladesh, underwent detailed
      examination and lens grading by the same certified grader using Lens
      Opacification Classification System III. Data were analysed using univariate and
      multivariable logistic regression analyses. RESULTS: Considerable difficulties
      were encountered in recruiting the sample in both locations. 372 Bangladeshis
      aged 40-70 years were examined: 131 in London and 241 in Bangladesh. Having never
      migrated from Bangladesh was an independent risk factor for opacities (OR 7.6;
      95% CI 3.6 to 15.9; p=0.001) as were age (OR 7.1; 95% CI 4.0 to 12.7; p=0.001)
      and diabetes (OR 2.5; 95% 1.0 to 6.0; p=0.04). The odds of LO were lower among
      those who had lived in the UK for a higher proportion of their life (OR 0.96; 95%
      CI 0.93 to 0.99; p=0.01), but this was not significant after adjusting for age
      and diabetes (OR 0.97; 95% CI 0.94 to 1.01; p=0.16). DISCUSSION: The study
      highlights the challenges of migration studies, and of studies involving ethnic
      minorities. Preliminary findings suggest that migration to the UK is protective
      for LO despite a significantly higher rate of diabetes in the UK. A larger study
      is warranted based on these preliminary findings.

PMID- 25563767
TI  - Telemedicine for detecting diabetic retinopathy: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To determine the diagnostic accuracy of telemedicine in various
      clinical levels of diabetic retinopathy (DR) and diabetic macular oedema (DME).
      METHODS: PubMed, EMBASE and Cochrane databases were searched for telemedicine and
      DR. The methodological quality of included studies was evaluated using the
      Quality Assessment for Diagnostic Accuracy Studies (QUADAS-2). Measures of
      sensitivity, specificity and other variables were pooled using a random effects
      model. Summary receiver operating characteristic curves were used to estimate
      overall test performance. Meta-regression and subgroup analyses were used to
      identify sources of heterogeneity. Publication bias was evaluated using Stata
      V.12.0. RESULTS: Twenty articles involving 1960 participants were included.
      Pooled sensitivity of telemedicine exceeded 80% in detecting the absence of DR,
      low- or high-risk proliferative diabetic retinopathy (PDR), it exceeded 70% in
      detecting mild or moderate non-proliferative diabetic retinopathy (NPDR), DME and
      clinically significant macular oedema (CSME) and was 53% (95% CI 45% to 62%) in
      detecting severe NPDR. Pooled specificity of telemedicine exceeded 90%, except in
      the detection of mild NPDR which reached 89% (95% CI 88% to 91%). Diagnostic
      accuracy was higher with digital images obtained through mydriasis than through
      non-mydriasis, and was highest when a wide angle (100-200 degrees ) was used
      compared with a narrower angle (45-60 degrees , 30 degrees  or 35 degrees ) in
      detecting the absence of DR and the presence of mild NPDR. No potential
      publication bias was detected. CONCLUSIONS: The diagnostic accuracy of
      telemedicine using digital imaging in DR is overall high. It can be used widely
      for DR screening. Telemedicine based on the digital imaging technique that
      combines mydriasis with a wide angle field (100-200 degrees ) is the best choice
      in detecting the absence of DR and the presence of mild NPDR.

PMID- 25563769
TI  - Bevacizumab for metastatic colon cancer: does patient BMI influence survival?
AB  - Adipose tissue is considered to have endocrine properties, including factors that
      are considered to have angiogenic activity. The current study aimed to evaluate
      whether there was a difference in the efficacy of bevacizumab for metastatic
      colon cancer patients according to their BMI (kg/m). A retrospective review of
      the medical records of consecutive patients who were treated with bevacizumab
      from diagnosis for metastatic colon cancer between 2005 and 2011 was carried out.
      Data extracted from medical files included demographics, height, weight,
      comorbidities, treatment protocols, time to tumor progression (TTP), and time of
      death. Variables were further evaluated with respect to TTP and overall survival
      (OS). The final analysis included 184 patients. The median TTP was 11.7 months
      and the median survival was 27.6 months. Chemotherapy dose reduction [P>0.001,
      hazard ratio (HR)=0.6, 95% confidence interval (CI) 0.4-0.8] and male sex
      (P=0.03, HR=0.7, 95% CI 0.5-1.0) predicted shorter TTP. Multivariate analysis
      indicated that metastatic disease at initial presentation and/or diabetes were
      associated with worse OS: the median OS for diabetes was 20 versus 28.3 months
      for patients without diabetes (P=0.008, HR=2, 95% CI 1.2-3.4) and 23 months for
      patients with metastatic disease at initial presentation versus 31.4 months for
      recurrent disease (P=0.008, HR=1.6, 95% CI 1.1-2.2). No differences were found
      for different BMIs subdivided into groups with respect to OS (P=0.84) or TTP
      (P=0.75). Our study did not show that bevacizumab is less effective in patients
      with a high BMI. It did show that diabetes and/or metastatic disease at initial
      diagnosis are associated with a poorer outcome. 

PMID- 25563770
TI  - Inhibition of NADPH oxidase protects against metastasis of human lung cancer by
      decreasing microRNA-21.
AB  - The objective of this study was to detect the effect of NADPH oxidase (NOX)
      inhibition on metastasis of lung cancer. Primary human lung cancer cells were
      isolated from surgical tissues using the Cancer Cell Isolation Kit. Invasion was
      detected using the BD Biocoat Matrigel Invasion Chamber assay. Expressions of
      microRNA-21 (miR-21), PTEN, MMP9, and p47 were detected by qPCR. Groups of nude
      mice were challenged with A549 cells with or without DPI and detected for tumor
      metastasis and survival. NOX inhibition in human lung cancer cells significantly
      reduced their invasive potential in vitro. NOX inhibition in vivo led to
      decreased metastasis of human lung cancer and prolonged the survival time of
      tumor-bearing nude mice. Further, NOX inhibition resulted in decreased expression
      of miR-21 in human lung cancer cells. Increased expression of miR-21 abrogated
      the effect of NOX inhibitor on metastasis of human lung cancer in vitro and in
      vivo. Decreased expression of miR-21 facilitated the effect of NOX inhibitor on
      metastasis of human lung cancer in vitro and in vivo. Furthermore, increased
      expression of PTEN and decreased expression of MMP9 were observed in human lung
      cancer cells in response to NOX inhibition. Finally, close correlations of miR-21
      expression levels with NADPH oxidase expression level and differentiation state
      of tumor cells were observed in lung cancer patients. Inhibition of NADPH oxidase
      protected against metastasis of human lung cancer cells by decreasing miR-21
      expression, which could facilitate the understanding of lung cancer pathogenesis
      and provided clues for the development of novel therapeutics for lung cancer
      patients. 

PMID- 25563771
TI  - A comprehensive study of sulfonated carbon materials as conductive composites for
      polymer solar cells.
AB  - Sulfonated carbon nanotubes (S-CNTs) and sulfonated graphene (S-Gra) with
      superior dispersibility were successfully prepared to modify poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) for applications in
      polymer solar cells (PSCs). The synergetic effect between S-CNTs/S-Gra and
      PEDOT:PSS could remove excess insulating PSS chains leading to an obvious phase
      separation between the PEDOT and PSS chains, which allows the formation of more
      conductive PEDOT channels. The PEDOT:PSS (Clevios PH 4083):S-CNTs with well
      matched work function, favorable morphology, optimized hydrophobicity and
      superior hole mobility is demonstrated to be an excellent hole transport layer
      (HTL) for PSCs. However, the PEDOT:PSS (Clevios PH 4083) modified by sulfonated
      graphene with stacked and wrinkled lamellae as an HTL renders a rough morphology
      and has a negative impact on the morphology of the active layer, consequently
      resulting in a poor device performance. Excitingly, PEDOT:PSS (Clevios PH 1000)
      modified with S-Gra shows high conductivity, because the sulfonated graphene
      lamellae contribute to the connection between the insulator and conductive PEDOT
      islands and improves the charge conduction. The PH1000:S-Gra with multiple layers
      presents excellent electrical conductive properties and a high transmittance
      (sheet resistance of ~45 Omega sq(-1) and transmittance of ~85.5% at 550 nm),
      which possess great potential for its application as a transparent conductive and
      flexible electrode in organic electronics. 

PMID- 25563772
TI  - An uncommon complication of staphylococcal pneumonia: pneumopericardium with
      cardiac tamponade.

PMID- 25563773
TI  - A chest physician's guide to mechanisms of sinonasal disease.
AB  - The upper and lower airways are closely linked from an anatomical, histological
      and immunological point of view, with inflammation in one part of the airways
      influencing the other part. Despite the concept of global airway disease, the
      upper airways tend to be overlooked by respiratory physicians. We provide a
      clinical overview of the most important and recent insights in rhinitis and
      rhinosinusitis in relation to lower airway disease. We focus on the various
      exogenous and endogenous factors that play a role in the development and
      aggravation of chronic upper airway inflammation. In addition to the classical
      inhaled allergens or microorganisms with well-defined pathophysiological
      mechanisms in upper airway disease, environmental substances such as cigarette
      smoke, diesel exhaust particles and occupational agents affecting lower airway
      homeostasis have recently gained attention in upper airway research. We are only
      at the beginning of understanding the complex interplay between exogenous and
      endogenous factors like genetic, immunological and hormonal influences on chronic
      upper airway inflammation. From a clinical perspective, the involvement of upper
      and lower airway disease in one patient can only be fully appreciated by doctors
      capable of understanding the interplay between upper and lower airway
      inflammation. 

PMID- 25563774
TI  - Iron and copper in progressive demyelination--New lessons from Skogholt's
      disease.
AB  - The pathophysiological mechanisms of progressive demyelinating disorders
      including multiple sclerosis are incompletely understood. Increasing evidence
      indicates a role for trace metals in the progression of several neurodegenerative
      disorders. The study of Skogholt disease, a recently discovered demyelinating
      disease affecting both the central and peripheral nervous system, might shed some
      light on the mechanisms underlying demyelination. Cerebrospinal fluid iron and
      copper concentrations are about four times higher in Skogholt patients than in
      controls. The transit into cerebrospinal fluid of these elements from blood
      probably occurs in protein bound form. We hypothesize that exchangeable fractions
      of iron and copper are further transferred from cerebrospinal fluid into myelin,
      thereby contributing to the pathogenesis of demyelination. Free or weakly bound
      iron and copper ions may exert their toxic action on myelin by catalyzing
      production of oxygen radicals. Similarities to demyelinating processes in
      multiple sclerosis and other myelinopathies are discussed. 

PMID- 25563776
TI  - [Centralisation of treatment of ruptured aneurysm].
AB  - In the future, patients with a ruptured aneurysm will be treated at fewer
      hospitals in the Netherlands. Although there is a search for scientific support
      for this, the reason for centralisation is obvious: reduction of costs and
      reduction of workload for vascular surgeons during night and weekend shifts.
      Already there are a number of examples of regionally organised vascular surgeons
      who treat their patients with a ruptured aneurysm with great satisfaction and
      with good results. 

PMID- 25563775
TI  - Virtual intervention to support self-management of antiretroviral therapy among
      people living with HIV.
AB  - BACKGROUND: Living with human immunodeficiency virus (HIV) necessitates long-term
      health care follow-up, particularly with respect to antiretroviral therapy (ART)
      management. Taking advantage of the enormous possibilities afforded by
      information and communication technologies (ICT), we developed a virtual nursing
      intervention (VIH-TAVIE) intended to empower HIV patients to manage their ART and
      their symptoms optimally. ICT interventions hold great promise across the entire
      continuum of HIV patient care but further research is needed to properly evaluate
      their effectiveness. OBJECTIVE: The objective of the study was to compare the
      effectiveness of two types of follow-up--traditional and virtual--in terms of
      promoting ART adherence among HIV patients. METHODS: A quasi-experimental study
      was conducted. Participants were 179 HIV patients on ART for at least 6 months,
      of which 99 were recruited at a site offering virtual follow-up and 80 at another
      site offering only traditional follow-up. The primary outcome was medication
      adherence and the secondary outcomes were the following cognitive and affective
      variables: self-efficacy, attitude toward medication intake, symptom-related
      discomfort, stress, and social support. These were evaluated by self-administered
      questionnaire at baseline (T0), and 3 (T3) and 6 months (T6) later. RESULTS: On
      average, participants had been living with HIV for 14 years and had been on ART
      for 11 years. The groups were highly heterogeneous, differing on a number of
      sociodemographic dimensions: education, income, marital status, employment
      status, and living arrangements. Adherence at baseline was high, reaching 80%
      (59/74) in the traditional follow-up group and 84% (81/97) in the virtual follow
      up group. A generalized estimating equations (GEE) analysis was run, controlling
      for sociodemographic characteristics at baseline. A time effect was detected
      indicating that both groups improved in adherence over time but did not differ in
      this regard. Improvement at 6 months was significantly greater than at 3 months
      in both groups. Analysis of variance revealed no significant group-by-time
      interaction effect on any of the secondary outcomes. A time effect was observed
      for the two kinds of follow-ups; both groups improved on symptom-related
      discomfort and social support. CONCLUSIONS: Results showed that both
      interventions improved adherence to ART. Thus, the two kinds of follow-up can be
      used to promote treatment adherence among HIV patients on ART.

PMID- 25563778
TI  - [Salt and hypertension: a need for reduction on a population level?].
AB  - The average salt intake in the Netherlands is well above the nationally
      recommended maximum intake of 6 grams per day. People with high intakes,
      especially if they have hypertension or type 2 diabetes mellitus and/or are older
      than 50 years of age are advised to lower their salt intake. Decreasing the
      intake of highly processed foods to which salt has been added and lowering the
      salt content of these foods seems to be sensible advice on a population level.
      Salt in food is directly related to blood pressure but also increases the
      palatability of processed foods and increases thirst, which may contribute to
      obesity. Reductions in salt intake should be accompanied by an increase in food
      rich in potassium such as vegetables, avoidance of excessive alcohol intake and
      the maintenance of a healthy weight. This strategy would not only be beneficial
      for improved blood pressure control but would also contribute to the general
      prevention of non-communicable diseases. 

PMID- 25563779
TI  - [Idiopathic intracranial hypertension and obesity].
AB  - BACKGROUND: Idiopathic intracranial hypertension (IIH) is a neurological syndrome
      characterized by elevated intracranial pressure in the absence of intracerebral
      abnormalities or hydrocephalus. CASE DESCRIPTION: A 17-year-old girl gained more
      than 25 kg in weight during treatment with risperidone and subsequently developed
      headache, diplopia and loss of vision due to IIH. After insertion of a
      ventriculoperitoneal drain and discontinuation of risperidone she lost weight and
      her symptoms improved. Her visual functions recovered almost fully during follow
      up. CONCLUSION: Patients with IIH are mainly overweight young women who present
      with raised intracranial pressure evidenced by headache, nausea, vomiting and
      vision disturbances. Prescribed medication-induced weight gain may lead to IIH.
      Treatment of IIH should be focused on the prevention of severe and irreversible
      loss of vision.

PMID- 25563780
TI  - [Treatment of breakthrough pain in cancer patients].
AB  - Pain is common in patients with cancer (33-64%) and can be divided into
      background and breakthrough pain (BTP). BTP is a passing, acute pain that occurs
      despite the use of analgesia to control background pain. BTP may arise
      spontaneously or be provoked by certain movements or activities. It lasts 30-60
      minutes and is generally self-limiting and is often undertreated. We describe 2
      patients aged 68 and 57 years with metastatic disease who were admitted for pain
      management. BTP was inadequately managed during their hospital stay. Both
      patients had to wait too long before they received their BTP medication, causing
      the BTP to have passed its peak. After consultation with their nurses, both
      patients were allowed to have one dose of breakthrough medication in advance,
      which resulted in better treatment of their BTP. Every hospitalized patient with
      BTP should have one dose of breakthrough medication ready for taking in advance. 

PMID- 25563781
TI  - [A woman with ischemia of the eyes and the left arm].
AB  - We saw a 23-year-old women with orthostasis, visual disturbances and pale
      discoloration of fingers on the left hand. Arterial pulsations were absent on
      both carotid, radial and ulnar arteries. Inflammatory parameters were raised and
      on funduscopy there was retinal ischemia. On FDG-PET/CT the diagnosis of Takayasu
      arteritis was made. 

PMID- 25563782
TI  - [When to carry out contact investigations in shigellosis: no need for extensive
      contact investigations in solitary cases].
AB  - In the revised Dutch guidelines, faeces testing for Shigella is advised for all
      household contacts if the index person is less than 6 years old and for persons
      with symptoms. We argue that in most cases there is no need for faeces testing.
      Clusters of shigelloses have become rare, and hygienic measures are sufficient to
      prevent transmission. The statistical significance of shigella transmission in
      children under 6 years old, on which the revised guideline is based, has no
      clinical relevance. In fact, the infection rate is only 7% even among the high
      risk contacts of the index patients under 6 years old and only 1 infection per 4
      index persons (25/104). Hygienic measures and exclusion from childcare centres or
      school in the event of symptoms are sufficient measures to prevent transmission. 

PMID- 25563784
TI  - [Use the Netherlands Triage Standard for children].
AB  - Studies have shown that the reliability and validity of the Netherlands Triage
      Standard (NTS) is comparable to the Manchester Triage System. The NTS has good
      sensitivity and specificity in the emergency room. The Dutch Society of Emergency
      and Accident Nurses, the Dutch College of General Practitioners and Ambulancezorg
      Nederland use the NTS as the guideline for both physical and telephone triage in
      ambulance care, primary care and hospital care with the competence of the triage
      nurse in a pivotal role. 

PMID- 25563783
TI  - [A man with a raised upper arm].
AB  - A 43-year-old man presented at our emergency department with a painful shoulder
      after a fall with his arm in abduction. Clinical presentation was typical for a
      luxatio erecta without evidence for neurovasculair damage. It is a rare but
      important diagnosis because of the high risk of plexus injury. 

PMID- 25563785
TI  - [A paradox: sarcoidosis in an HIV-positive patient].
AB  - BACKGROUND: In view of the diminished number of CD4+ lymphocytes, the co
      existence of an HIV infection and sarcoidosis seems paradoxical. Immune
      reconstitution inflammatory syndrome (IRIS) may be observed in response to anti
      retroviral therapy (ART). According to the conventional definition, this is
      caused by an overwhelming immune response to an already present or to a new
      agent. CASE DESCRIPTION: We describe the case of a 47-year-old HIV-positive
      patient, who presented with an exacerbation of his sarcoidosis nine months after
      initiation of ART. Based on the time course and the dynamics of the CD4+
      lymphocyte count, this presentation of disease can be placed in the context of
      IRIS. CONCLUSION: The presentation or exacerbation of sarcoidosis after
      initiation of antiretroviral therapy in HIV-positive patients with a low CD4+
      count at start of therapy can be placed in the context of IRIS.

PMID- 25563786
TI  - [A neonate with an interlabial cyst].
AB  - During a routine physical examination of a term, healthy neonate of Somalian
      origin we observed an anteriorly located interlabial yellow cyst with visible
      vascularisation on the outer surface. It caused lateralisation of the urinary
      meatus without notable obstruction. A Skene's duct cyst, or paraurethral cyst,
      was clinically diagnosed with spontaneous regression. This is a self-limiting
      phenomenon of unknown origin that rarely requires surgical drainage in case of
      urinary obstruction. 

PMID- 25563787
TI  - [The pros and cons of angioplasty in stable coronary artery disease].
AB  - American research demonstrated that 1 out of 4 patients undergoes diagnostic
      coronary angiography without clear evidence of symptoms or objective signs of
      ischaemia, leading to unnecessary angioplasties in a substantial number of
      patients. A second study, published simultaneously, demonstrated that proper
      patient education could decrease the rates of angioplasty in patients with stable
      coronary artery disease significantly. In the present editorial we critically
      assess both publications and put them in perspective to current clinical practice
      in the Netherlands along with the European guidelines for myocardial
      revascularization. 

PMID- 25563788
TI  - [Use the Manchester Triage System for children].
AB  - Today, in 2014, the Manchester Triage System is an evidence-based triage system
      for the emergency room. It has been nationally and internationally validated and
      is safe for children. Why use the non-validated Netherlands Triage Standard that
      has no specific triage that has been suitably adapted and tested for children? 

PMID- 25563789
TI  - [Patients are not prepared to choose: another example of a failing market?].
AB  - The Netherlands has a demand-driven health care system based on market
      mechanisms. However, the system is a hybrid between two potential situations: one
      in which healthcare insurance companies have a leading role, with consumers and
      patients choosing for the company that most suits them, and one in which patients
      have a leading role and select their favourite caregiver, whereby the insurance
      company has to follow. Current research concludes that the vast majority of
      patients are not able or even willing to choose, but instead place their trust in
      referring physicians and local hospitals. Additionally, many patients feel that
      they are not capable of making informed choices. If patients cannot or do not
      want to choose their healthcare providers, then one of the mainstays of a market
      based health care system should perhaps be seriously re-evaluated. 

PMID- 25563791
TI  - Dynamic membrane patterning, signal localization and polarity in living cells.
AB  - We review the molecular and physical aspects of the dynamic localization of
      signaling molecules on the plasma membranes of living cells. At the nanoscale,
      clusters of receptors and signaling proteins play an essential role in the
      processing of extracellular signals. At the microscale, "soft" and highly dynamic
      signaling domains control the interaction of individual cells with their
      environment. At the multicellular scale, individual polarity patterns control the
      forces that shape multicellular aggregates and tissues. 

PMID- 25563790
TI  - Nobiletin inhibits invasion and migration of human nasopharyngeal carcinoma cell
      lines by involving ERK1/2 and transcriptional inhibition of MMP-2.
AB  - OBJECTIVE: Nasopharyngeal carcinoma (NPC) is known for its high incidence of neck
      lymph node metastasis, which represents poor prognosis. Nobiletin is a citrus
      polymethoxyflavonoid that suppresses tumor growth and metastasis, both of which
      depend on angiogenesis in previous studies. However, the effect of Nobiletin on
      human NPC cells metastasis has not been clearly clarified. RESEARCH DESIGN AND
      METHODS: In this study, we determine the effects of Nobiletin on the migration
      and invasion in NPC cells. RESULTS: Nobiletin significantly inhibited
      migration/invasion capacities of HONE-1 and NPC-BM cell lines. The results of
      gelatin zymography and western blotting revealed that the activities and protein
      levels of the MMP-2 were inhibited by Nobiletin. Nobiletin also showed that
      inhibits phosphorylation of ERK1/2. Tests of the real-time PCR and promoter
      assays evaluated the inhibitory effects of Nobiletin on MMP-2 expression in human
      NPC cells. Nobiletin inhibits MMP-2 expression, up-regulating tissue inhibitor of
      metalloproteinase-2 and down-regulation of the transcription factors of NF-kappaB
      and activator protein 1 (AP-1) signaling pathways. Finally, an administration of
      Nobiletin effectively suppressed the tumor formation and metastasis in the NPC
      xenograft model in vivo. CONCLUSIONS: Nobiletin may have potential use as a chemo
      preventive agent against nasopharyngeal cancer metastasis.

PMID- 25563792
TI  - Computational analysis of auxin responsive elements in the Arabidopsis thaliana
      L. genome.
AB  - Auxin responsive elements (AuxRE) were found in upstream regions of target genes
      for ARFs (Auxin response factors). While Chip-seq data for most of ARFs are still
      unavailable, prediction of potential AuxRE is restricted by consensus models that
      detect too many false positive sites. Using sequence analysis of experimentally
      proven AuxREs, we revealed both an extended nucleotide context pattern for AuxRE
      itself and three distinct types of its coupling motifs (Y-patch, AuxRE-like, and
      ABRE-like), which together with AuxRE may form the composite elements.
      Computational analysis of the genome-wide distribution of the predicted AuxREs
      and their impact on auxin responsive gene expression allowed us to conclude that:
      (1) AuxREs are enriched around the transcription start site with the maximum
      density in 5'UTR; (2) AuxREs mediate auxin responsive up-regulation, not down
      regulation. (3) Directly oriented single AuxREs and reverse multiple AuxREs are
      mostly associated with auxin responsiveness. In the composite AuxRE elements
      associated with auxin response, ABRE-like and Y-patch are 5'-flanking or
      overlapping AuxRE, whereas AuxRE-like motif is 3'-flanking. The specificity in
      location and orientation of the coupling elements suggests them as potential
      binding sites for ARFs partners. 

PMID- 25563793
TI  - The role of TREM-2 in internalization and intracellular survival of Brucella
      abortus in murine macrophages.
AB  - Triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface
      receptor primarily expressed on macrophages and dendritic cells. TREM-2 functions
      as a phagocytic receptor for bacteria as well as an inhibitor of Toll like
      receptors (TLR) induced inflammatory cytokines. However, the role of TREM-2 in
      Brucella intracellular growth remains unknown. To investigate whether TREM-2 is
      involved in Brucella intracellular survival, we chose bone marrow derived
      macrophages (BMDMs), in which TREM-2 is stably expressed, as cell model. Colony
      formation Units (CFUs) assay suggests that TREM-2 is involved in the
      internalization of Brucella abortus (B. abortus) by macrophages, while silencing
      of TREM-2 decreases intracellular survival of B. abortus. To further study the
      underlying mechanisms of TREM-2-mediated bacterial intracellular survival, we
      examined the activation of B. abortus-infected macrophages through determining
      the kinetics of activation of the three MAPKs, including ERK, JNK and p38, and
      measuring TNFalpha production in response to lipopolysaccharide (LPS) of Brucella
      (BrLPS) or B. abortus stimulation. Our data show that TREM-2 deficiency promotes
      activation of Brucella-infected macrophages. Moreover, our data also demonstrate
      that macrophage activation promotes killing of Brucella by enhancing nitric
      oxygen (NO), but not reactive oxygen species (ROS) production, macrophage
      apoptosis or cellular death. Taken together, these findings provide a novel
      interpretation of Brucella intracellular growth through inhibition of NO
      production produced by TREM-2-mediated activated macrophages. 

PMID- 25563796
TI  - Vitamin D deficiency and cardiovascular disease in postmenopausal women:
      contributions from human and nonhuman primate studies.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death among
      American postmenopausal women and all adult Americans. The medical community and
      the lay community have recently become intrigued with vitamin D and its potential
      role in reducing the risk of CVD. Research findings from multiple retrospective
      studies, few prospective studies, and recent nonhuman primate studies have been
      inconsistent and conflicting. The objective of this study is to review what is
      known about the topic, what questions remain unanswered, and where the research
      community should be focusing. METHODS: A literature search was conducted through
      PubMed and Google Scholar up to August 1, 2014. One hundred six articles,
      including 18 double-blind, placebo-controlled, randomized clinical trials,
      relevant to the study topic were identified. All studies were stratified based on
      study design and primary outcome. The effects of vitamin D on CVD were reviewed
      and summarized. RESULTS: Although there is an abundance of observational studies
      suggesting an association with CVD protection, the most well-controlled
      randomized human trial data available show no benefit of vitamin D on CVD.
      However, highly controlled nonhuman primate studies indicate a beneficial
      relationship. CONCLUSIONS: Well-designed research, with CVD as primary outcome,
      is needed to help bridge the gap in our knowledge on this topic. In the meantime,
      caution should be applied to avoid overdiagnosis and overtreatment of vitamin D
      deficiency.

PMID- 25563794
TI  - Palmiwon attenuates hepatic lipid accumulation and hyperlipidemia in a menopausal
      rat model.
AB  - OBJECTIVE: We examined the phytoestrogenic effects of palmiwon on breast
      carcinoma, lipid accumulation in methyl-beta-cyclodextrin-induced HepG2 cells,
      and lipid-related diseases in a rat model of menopausal hyperlipidemia. METHODS:
      E-Screen assay was used to screen for phytoestrogens, especially those with
      antiestrogenic activity, in MCF-7 cells. Oil Red O staining and intracellular
      cholesterol analyses were used to quantify cellular cholesterol levels. 3-Hydroxy
      3-methyl glutaryl coenzyme A reductase assay was used to measure enzyme activity.
      The levels of phosphorylated adenosine monophosphate-activated protein kinases
      and products of genes involved in cholesterol synthesis were measured by Western
      blot analysis. Thirty rats were either ovariectomized or sham-operated and
      randomly assigned to four groups (n = 5)-Sham, OVX, OVX-SV, or OVX-PMW (50, 150,
      or 450 mg/kg) group-for 8 weeks. A number of targets associated with lipid
      related diseases were examined to confirm the estrogenic effects of palmiwon.
      RESULTS: Palmiwon showed antiestrogenic activity in MCF-7 cells. Palmiwon
      decreased lipid accumulation, total cholesterol levels, and low-density
      lipoprotein/very-low-density lipoprotein levels in HepG2 cells. Moreover,
      palmiwon reversed the effects of methyl-beta-cyclodextrin on cholesterol
      synthesis regulators and inhibited the activity of 3-hydroxy-3-methyl glutaryl
      coenzyme A reductase. Phosphorylation of adenosine monophosphate-activated
      protein kinase was stimulated by palmiwon. In ovariectomized rats, palmiwon
      reduced retroperitoneal and perirenal fat accumulation, serum lipids, atherogenic
      index, cardiac risk factor score, intima-media thickness, and nonalcoholic
      steatohepatitis scores. CONCLUSIONS: These results indicate that palmiwon
      inhibits lipid accumulation without estrogenic activity in the breast. Therefore,
      palmiwon may have potential as a therapeutic agent for the treatment of
      hyperlipidemia in postmenopausal women.

PMID- 25563795
TI  - Dietary changes associated with improvement of metabolic syndrome components in
      postmenopausal women receiving two different nutrition interventions.
AB  - OBJECTIVE: This study aims to examine the association between dietary changes and
      improvement of metabolic syndrome components in Mexican postmenopausal women
      receiving two different nutrition interventions. METHODS: Women (n = 118) with
      metabolic syndrome were randomly assigned to group 1 (n = 63; structured
      hypocaloric diet) or group 2 (n = 55; behavioral therapy). Metabolic and
      nutrition assessment was performed at baseline and after 2, 4, and 6 months of
      intervention. Dietary changes throughout the study and achievement of
      cardioprotective dietary goals were assessed at the end of the intervention.
      RESULTS: There was a significant increase in the number of women who met
      recommended servings for fruits/vegetables, low-fat dairy, and sugars in both
      groups. In group 1, elimination of high-energy refined grains increased the
      probability of having normal fasting glucose (relative risk, 1.514; 95% CI, 0.989
      2.316; P = 0.035). In this group, women who met the low-fat dairy goal at the end
      of the study had lower diastolic blood pressure (P = 0.012) and higher high
      density lipoprotein cholesterol (P = 0.001). In group 2, women who met the high
      fat dairy goal had greater probability of having normal fasting glucose (relative
      risk, 1.915; 95% CI, 1.123-3.266; P = 0.026). In all women, exclusion of high-fat
      dairy decreased by 60% the probability of having impaired fasting glucose
      (relative risk, 0.40; 95% CI, 0.181-0.906; P = 0.028). CONCLUSIONS: Both
      strategies promote achievement of cardioprotective dietary goals for
      fruits/vegetables, sugars, soda and sweetened beverages, low-fat dairy, and high
      energy refined grains, and improve some metabolic syndrome components.
      Elimination of high-fat dairy decreases the risk of impaired fasting glucose.
      Dietary strategies should be flexible and individualized based on metabolic
      profile.

PMID- 25563797
TI  - Endothelial function in postmenopausal women with nighttime systolic
      hypertension.
AB  - OBJECTIVE: Hypertension becomes more prevalent in women during their
      postmenopausal years. Nighttime systolic blood pressure (SBP) is especially
      predictive of adverse cardiac events, and the relationship between rising
      nighttime SBP and cardiovascular risk increases more rapidly in women compared
      with men. The reasons for the prognostic significance of nighttime SBP are not
      completely known but may involve vascular endothelial dysfunction. The purposes
      of this study were to examine the relationship between nighttime SBP and
      endothelial function, as assessed by brachial artery flow-mediated dilation
      (FMD), and to determine whether postmenopausal women with nighttime hypertension
      (SBP >=120 mm Hg) evidenced greater endothelial dysfunction compared with women
      with normal nighttime SBP. METHODS: One hundred postmenopausal women (mean [SD]
      age, 65.8 [7.5] y; mean [SD] body mass index, 28.3 [4.7] kg/m; hypertension, 47%;
      coronary artery disease, 51%; mean [SD] clinic SBP, 137 [17] mm Hg; mean [SD]
      clinic diastolic blood pressure, 67 [11] mm Hg; nighttime hypertension, 34 women)
      underwent 24-hour ambulatory blood pressure monitoring, actigraphy, and brachial
      artery FMD assessment. RESULTS: Multivariate regression models showed that higher
      nighttime SBP and larger baseline artery diameter were inversely related to FMD.
      Nighttime SBP and baseline artery diameter accounted for 23% of the variance in
      FMD. After adjustment for baseline artery diameter, women with nighttime
      hypertension had lower mean (SD) FMD than women with normal nighttime SBP (2.95%
      [0.65%] vs 5.52% [0.46%], P = 0.002). CONCLUSIONS: Nighttime hypertension is
      associated with reduced endothelial function in postmenopausal women. Research
      examining the therapeutic benefits of nighttime hypertension treatment on
      endothelial function and future cardiovascular risk in postmenopausal women is
      warranted.

PMID- 25563798
TI  - Calibration of an intrahost malaria model and parameter ensemble evaluation of a
      pre-erythrocytic vaccine.
AB  - BACKGROUND: A pre-erythrocytic vaccine could provide a useful tool for burden
      reduction and eventual eradication of malaria. Mathematical malaria models
      provide a mechanism for evaluating the effective burden reduction across a range
      of transmission conditions where such a vaccine might be deployed. METHODS: The
      EMOD model is an individual-based model of malaria transmission dynamics,
      including vector lifecycles and species-specific behaviour, coupled to a
      mechanistic intrahost model of malaria parasite and host immune system dynamics.
      The present work describes the extension of the EMOD model to include diagnoses
      of severe malaria and iterative calibration of the immune system parameters and
      parasite antigenic variation to age-stratified prevalence, incidence and severe
      disease incidence data obtained from multiple regions with broadly varying
      transmission conditions in Africa. An ensemble of calibrated model parameter sets
      is then employed to evaluate the potential impact of routine immunization with a
      pre-erythrocytic vaccine. RESULTS: The reduction in severe malaria burden
      exhibits a broad peak at moderate transmission conditions. Under sufficiently
      intense transmission, a vaccine that reduces but does not eliminate the
      probability of acquisition from a single challenge bite may delay infections but
      produces minimal or no net reduction. Conversely, under sufficiently weak
      transmission conditions, a vaccine can provide a high fractional reduction but
      avert a relatively low absolute number of cases due to low baseline burden.
      CONCLUSIONS: Roll-out of routine immunization with pre-erythrocytic malaria
      vaccines can provide substantial burden reduction across a range of transmission
      conditions typical to many regions in Africa.

PMID- 25563799
TI  - Chitotriosidase and lysosomal enzymes as potential biomarkers of disease
      progression in amyotrophic lateral sclerosis: a survey clinic-based study.
AB  - The aim of this study was to determine if blood chitotriosidase (Chit) activity
      and lysosomal enzyme levels might represent markers of disease activity and
      progression in amyotrophic lateral sclerosis (ALS). It is a survey clinic-based
      study performed in a tertiary ALS centre. Blood samples were obtained from 76
      patients with ALS in different stages of the disease and from 106 healthy
      individuals serving as controls. Chit activity and the levels of acid alpha
      glucosidase, acid alpha-galattosidase A, beta-glucocerebrosidase, and alpha-l
      iduronidase were detected using the dried blood spots (DBS) technique. The CHIT1
      genotype for exon 10 duplication and for the p.G102S variant was also determined.
      Chit activity was significantly higher in ALS patients than in healthy
      individuals. This difference was independent of the genotypes at CHIT1 functional
      variants. Chit were significantly higher in 34 rapidly progressing patients as
      compared to 42 with slowly progressive disease. Acid alpha-glucosidase was higher
      than normal and significantly correlated with the severity of the disease.
      Glucocerebrosidase and alpha-l-iduronidase activity were significantly lower in
      patients than in the controls. Alpha-galactosidase A was higher than normal only
      in rapidly progressing patients. We have employed a very simple and affordable
      laboratory test to measure blood Chit and lysosomal enzymes activity which could
      be easily included in the screening of ALS patients recruited in clinical trials.
      Remarkably, high levels of chitinase and alpha-galactosidase A could help to
      distinguish patients with fast progression from those with slow progression of
      the disease and possibly to follow the effects of treatments on neuroinflammation
      and autophagy. 

PMID- 25563801
TI  - A simple model for DNA bridging proteins and bacterial or human genomes: bridging
      induced attraction and genome compaction.
AB  - We present computer simulations of the phase behaviour of an ensemble of proteins
      interacting with a polymer, mimicking non-specific binding to a piece of
      bacterial DNA or eukaryotic chromatin. The proteins can simultaneously bind to
      the polymer in two or more places to create protein bridges. Despite the lack of
      any explicit interaction between the proteins or between DNA segments, our
      simulations confirm previous results showing that when the protein-polymer
      interaction is sufficiently strong, the proteins come together to form clusters.
      Furthermore, a sufficiently large concentration of bridging proteins leads to the
      compaction of the swollen polymer into a globular phase. Here we characterise
      both the formation of protein clusters and the polymer collapse as a function of
      protein concentration, protein-polymer affinity and fibre flexibility. 

PMID- 25563800
TI  - Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia linked
      CSF1R mutation: Report of four Korean cases.
AB  - We describe detailed clinical, biochemical, neuroimaging and neuropathological
      features in adult-onset leukoencephalopathy with axonal spheroids and pigmented
      glia (ALSP), encompassing hereditary diffuse leukoencephalopathy with axonal
      spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD), linked to
      colony-stimulating factor 1 receptor (CSF1R) mutations in four Korean cases.
      Clinical, biochemical, neuroimaging and neuropathological findings were obtained
      by direct evaluation and from previous medical records. The genetic analysis of
      the CSF1R gene was done in two autopsy-confirmed ALSP cases and two cases where
      ALSP was suspected based on the clinical and neuroimaging characteristics. We
      identified two known mutations: c.2342C>T (p.A781V) in one autopsy-proven HDLS
      and clinically ALSP-suspected case and c.2345G>A (p.R782H) in another autopsy
      proven POLD case. We also found a novel mutation (c.2296A>G; p.M766V) in a
      patient presenting with hand tremor, stuttering and hesitant speech, and abnormal
      behavior whose father died from a possible diagnosis of spinocerebellar ataxia.
      To the best of our knowledge, this is the first documented ALSP-linked CSF1R
      mutation in Korea and supports the suggestion that HDLS and POLD, with
      pathological characteristics that are somewhat different but which are caused by
      CSF1R mutations, are the same spectrum of disease, ALSP. 

PMID- 25563802
TI  - Organocatalytic one-pot 1,4-/1,6-/1,2-addition sequence for the stereocontrolled
      formation of six consecutive stereocenters.
AB  - An unprecedented stereoselective organocatalytic one-pot 1,4-/1,6-/1,2-addition
      sequence between beta-dicarbonyl compounds, beta-nitroalkenes and 4-nitro-5
      styrylisoxazoles sequentially catalyzed by low loading of a squaramide catalyst
      and an achiral base has been developed. The protocol opens an efficient entry to
      isoxazole bearing cyclohexanes with six consecutive stereogenic centers including
      one tetrasubstituted carbon in good yields and excellent diastereo- and
      enantioselectivities. 

PMID- 25563803
TI  - The anti-arrhythmic effect of chronic intermittent hypobaric hypoxia in rats with
      metabolic syndrome induced with fructose.
AB  - This study investigated the anti-arrhythmic effects from chronic intermittent
      hypobaric hypoxia (CIHH) and the cellular mechanisms in rats with metabolic
      syndrome. Male Sprague-Dawley rats were randomly distributed among the control,
      fructose-fed (fed with 10% fructose in the drinking water to induce metabolic
      syndrome), CIHH (42 days of hypobaric hypoxia treatment simulating an altitude of
      5000 m a.s.l.: PB = 404 mm Hg, PO2 = 84 mm Hg, 6 h per day), and the CIHH plus
      fructose (CIHH-F) groups. In anesthetized rats, the arrhythmia score was
      determined after 30 min of cardiac ischemia followed by 120 min of reperfusion.
      Action potentials (AP) were recorded from isolated ventricular papillary muscles.
      The arrhythmia score was much lower in CIHH-F rats than in the fructose-fed rats.
      Under basic conditions, AP duration (APD) was significantly shortened in fructose
      fed rats, but obviously prolonged in CIHH rats compared with that of the control
      rats. During ischemia, the AP amplitude, the maximal rate of rise of phase 0,
      APD, and resting potential, were lower in the control, fructose-fed, and CIHH-F
      groups, but were not changed in the CIHH rats. The lower AP during ischemia did
      not recover after washout for the fructose-fed rats. In conclusion, CIHH protects
      the heart against ischemia-reperfusion induced arrhythmia in rats with metabolic
      syndrome. This effect of CIHH is possibly related to baseline prolongation of the
      AP and attenuation of AP reduction during ischemia-reperfusion. 

PMID- 25563804
TI  - Active site-directed proteomic probes for adenylation domains in nonribosomal
      peptide synthetases.
AB  - We describe a general strategy for selective chemical labeling of individual
      adenylation (A) domains in nonribosomal peptide synthetases (NRPSs) using active
      site-directed proteomic probes coupled to the 5'-O-N
      (aminoacyl)sulfamoyladenosine (AMS) scaffold with a clickable benzophenone
      functionality. These proteomic tools can greatly facilitate the molecular
      identification, functional characterization, and profiling of virtually any kind
      of A domains of NRPS enzymes in complex biological systems. 

PMID- 25563805
TI  - Driving under the influence of alcohol in Cali, Colombia: prevalence and
      consumption patterns, 2013.
AB  - This study's goal was to establish the prevalence of driving under the influence
      of alcohol (DUI) and alcohol consumption patterns among drivers in Cali,
      Colombia, in 2013. A cross-sectional study based on a roadside survey using a
      stratified and multi-stage sampling design was developed. Thirty-two sites were
      chosen randomly for the selection of drivers who were then tested for blood
      alcohol concentration (BAC) and asked to participate in the survey. The
      prevalence of DUI was 0.88% (95% confidence intervals [95% CI] 0.26%-1.49%) with
      a lower prevalence when BAC was increasing. In addition, a higher prevalence was
      found during non-typical checkpoint hours (1.28, 95% CI -0.001%-0.03%). The
      overall prevalence is considered high, given the low alcohol consumption and
      vehicles per capita. Prevention measures are needed to reduce DUI during non
      typical checkpoints and ongoing studies are required to monitor the trends and
      enable the assessment of interventions. 

PMID- 25563806
TI  - Gene polymorphisms potentially related to the pharmacokinetics of clozapine: a
      systematic review.
AB  - Clozapine is currently the ultimate effective therapy for otherwise treatment
      refractory schizophrenia. However, the drug is also associated with many adverse
      effects, some of them potentially fatal. Thus, there is an unmet need to predict
      clinical response to clozapine. As the pharmacokinetics of clozapine vary
      considerably between and within individuals, there may be an association between
      genetic polymorphisms and clozapine plasma concentration and consequently,
      clinical response. We have reviewed studies that have investigated the
      association between clozapine metabolic pathways related to genes polymorphisms
      in relation to plasma clozapine concentration and clinical response. Overall,
      most of the studies reported negative results. The only gene polymorphism that
      has been found to be associated with clozapine plasma concentration and response
      was the ABCB1 gene, which codes for transmembrane transporters expressed in the
      bowel mucosa, blood-brain barrier, kidney and liver. More prospective
      longitudinal studies are needed to elucidate the possible role of the ABCB1
      polymorphism and transmembrane transporters in clozapine pharmacokinetics and
      clinical response.

PMID- 25563807
TI  - Inferring coarse-grain histone-DNA interaction potentials from high-resolution
      structures of the nucleosome.
AB  - The histone-DNA interaction in the nucleosome is a fundamental mechanism of
      genomic compaction and regulation, which remains largely unknown despite
      increasing structural knowledge of the complex. In this paper, we propose a
      framework for the extraction of a nanoscale histone-DNA force-field from a
      collection of high-resolution structures, which may be adapted to a larger class
      of protein-DNA complexes. We applied the procedure to a large crystallographic
      database extended by snapshots from molecular dynamics simulations. The
      comparison of the structural models first shows that, at histone-DNA contact
      sites, the DNA base-pairs are shifted outwards locally, consistent with locally
      repulsive forces exerted by the histones. The second step shows that the various
      force profiles of the structures under analysis derive locally from a unique,
      sequence-independent, quadratic repulsive force-field, while the sequence
      preferences are entirely due to internal DNA mechanics. We have thus obtained the
      first knowledge-derived nanoscale interaction potential for histone-DNA in the
      nucleosome. The conformations obtained by relaxation of nucleosomal DNA with high
      affinity sequences in this potential accurately reproduce the experimental values
      of binding preferences. Finally we address the more generic binding mechanisms
      relevant to the 80% genomic sequences incorporated in nucleosomes, by computing
      the conformation of nucleosomal DNA with sequence-averaged properties. This
      conformation differs from those found in crystals, and the analysis suggests that
      repulsive histone forces are related to local stretch tension in nucleosomal DNA,
      mostly between adjacent contact points. This tension could play a role in the
      stability of the complex. 

PMID- 25563808
TI  - Creased hydrogels as active platforms for mechanical deformation of cultured
      cells.
AB  - Cells cultured in vitro using traditional substrates often change their behavior
      due to the lack of mechanical deformation they would naturally experience in
      vivo. To mimic the in vivo mechanical environment, we design temperature
      responsive hydrogels with patterned surface creases as dynamic cell stretching
      devices. A one-step photolithographic method is first employed to pattern
      integrin-binding peptides on the gel, causing single cells or several-cell
      clusters to adhere to the surface in registry with creases. A variety of crease
      patterns are prescribed on a single substrate, enabling the mechanical
      deformation of cultured myoblast cells with different strain states and achieving
      tensile strain as high as 0.2. As creases provide large amplitude local
      deformation of the gel surface without the need for macroscopic deformation, can
      be formed on gels covering a wide range of modulus, and can be actuated using a
      variety of stimuli, they hold the potential to enable the design of high
      throughput and versatile platforms for mechano-biological studies. 

PMID- 25563809
TI  - Rhenium-catalyzed anti-Markovnikov addition reaction of methanetricarboxylates to
      unactivated terminal acetylenes.
AB  - A novel anti-Markovnikov addition reaction of methanetricarboxylates with
      terminal acetylenes under neutral conditions was achieved using a rhenium
      complex. This transformation represents a rare example of intermolecular anti
      Markovnikov addition of carbon nucleophiles to unactivated terminal acetylenes.
      1,3-Diesters having bulky substituents at the active methylene carbon are also
      applicable as substrates to provide anti-Markovnikov adducts as single regio- and
      stereoisomers. Preliminary mechanistic studies imply that the rhenium vinylidene
      species is the key intermediate in the current catalytic cycle. 

PMID- 25563810
TI  - Ethynylglycine synthon, a useful precursor for the synthesis of biologically
      active compounds: an update: part I: preparations of ethynylglycine synthon.
AB  - The ethynylglycine synthon {(R)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4
      ethynyloxazolidine} is a chiral compound with valuable synthetic interest. An
      update on the different routes for its synthesis is reviewed and discussed. 

PMID- 25563811
TI  - Hepatocellular carcinoma as a second primary cancer in patients with chronic
      hepatitis C virus infection.

PMID- 25563812
TI  - Long-term efficacy of endoscopic vacuum therapy for the treatment of colorectal
      anastomotic leaks.
AB  - BACKGROUND: Anastomotic leaks are a severe complication after colorectal surgery.
      We aimed to evaluate the long-term efficacy of endoscopic vacuum therapy for
      their treatment. METHODS: Retrospective review of a series of post-surgical
      colorectal leaks treated with endoscopic vacuum therapy, with minimum follow-up
      of 1 year. Generalized peritonitis or haemodynamic instability was considered
      contraindication to endoscopic treatment. RESULTS: Endoscopic vacuum therapy was
      applied in 14 patients with colorectal leak, in 2 cases complicated by recto
      vaginal fistula. Overall success rate was 79%, favoured by early beginning of
      treatment (90%) and presence of a stoma (100%) and no preoperative radiotherapy
      (86%). Median duration of treatment was 12.5 sessions (range 4-40). Median time
      for complete healing was 40.5 days (range 8-114), for a median cost of treatment
      of 3125 Euros. No complication related to endoscopic vacuum therapy was observed.
      Further surgery was required in 3 cases. CONCLUSION: Endoscopic vacuum therapy is
      a safe treatment for post-surgical leaks, with high success rates.

PMID- 25563813
TI  - Neuropeptides of the VIP family inhibit glioblastoma cell invasion.
AB  - Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating
      polypeptide (PACAP) are neuropeptides acting through VPAC1, VPAC2 and PAC1
      receptors (referred here as the VIP-receptor system). In the central nervous
      system, VIP and PACAP are involved in neurogenesis, cell differentiation and
      migration, suggesting that they could be implicated in the development of
      glioblastoma (GBM). The infiltrative nature of GBM remains a major problem for
      the therapy of these tumors. We previously demonstrated that the VIP-receptor
      system regulated cell migration of the human cell lines M059J and M059K, derived
      from a single human GBM. Here, we evaluated the involvement of the VIP-receptor
      system in GBM cell invasion. In Matrigel invasion assays, M059K cells that
      express more the VIP-receptor system than M059J cells were less invasive.
      Invasion assays performed in the presence of agonists, antagonists or anti-PACAP
      antibodies as well as experiments with transfected M059J cells overexpressing the
      VPAC1 receptor indicated that the more the VIP-receptor system was expressed and
      activated, the less the cells were able to invade. Western immunoblotting
      experiments revealed that the VIP-receptor system inactivated the signaling
      protein AKT. Invasion assays carried out in the presence of an AKT inhibitor
      demonstrated the involvement of this signaling kinase in the regulation of cell
      invasion by the VIP-receptor system in M059K cells. The inhibition by VIP of
      invasion and AKT was also observed in U87 cells. In conclusion, VIP and PACAP act
      as anti-invasive factors in different GBM cell lines, a function mediated by
      VPAC1 inhibition of AKT signaling in M059K cells.

PMID- 25563814
TI  - p-CREB expression in human meningiomas: correlation with angiogenesis and
      recurrence risk.
AB  - Despite total surgical resection, a percentage of meningiomas do unexpectedly
      recur. At present the prediction of recurrence risk and the management of
      recurrent tumours represent major issues in the patients affected by meningiomas.
      The present study aims at investigating the prognostic value of the expression of
      the phosphorylated transcription factor cyclic AMP responsive element binding
      protein (p-CREB) in a series of meningiomas of different histotype and grade.
      While no p-CREB expression was found in specimens of normal leptomeninges, 71 %
      of meningiomas in our cohort expressed p-CREB. In addition, nuclear expression of
      p-CREB was present in the endothelia of tumor vessels in all of the meningiomas,
      but not in the vessels of the non-neoplastic meninges. High expression of p-CREB
      was significantly more frequent in meningiomas showing atypical, chordoid or
      microcystic histotype (P = 0.0003), high histological grade (P < 0.0001), high Ki
      67 labeling index (P = 0.0001), high microvessel density counts (P < 0.0001) and
      high vascular endothelial growth factor expression (P = 0.0113). In addition,
      high p-CREB expression was significantly associated with the development of
      recurrences (P = 0.0031) and it was a significant negative, albeit not
      independent, prognostic factor for disease free survival in patients with
      meningiomas submitted to complete surgical removal (P = 0.0019). In conclusion,
      we showed that p-CREB is expressed in human meningiomas and that it represents a
      significant predictor of recurrence risk in these tumors. Due to its high
      expression in more aggressive tumors and in the tumor vessels, it may represent a
      novel therapeutic target in meningiomas.

PMID- 25563815
TI  - Prognostic marker analysis in pediatric intracranial ependymomas.
AB  - Histologic grading methods dependent upon H&E staining review have not been shown
      to reliably predict survival in children with intracranial ependymomas due to the
      subjectivity of the analytical methods. We hypothesized that the
      immunohistochemical detection of MIB-1, Tenascin C, CD34, VEGF, and CA IX may
      represent objective markers of post-operative survival (Progression Free and
      Overall Survival; PFS, OS) in these patients. Intracranial ependymomas from
      patients aged 22 years or less were studied. The original histologic grade was
      recorded, H&E sections were reviewed for vascular proliferation status, and
      immunohistochemistry was used to determine MIB-1, Tenascin C, CD34, VEGF, and CA
      IX status. Based upon the World Health Organization (WHO) grading system, 3 Grade
      I, 18 Grade II and 9 Grade III ependymomas were studied. Median follow-up time
      was 9.0 years; median PFS was, 6.1 years. Original WHO grade did not correlate
      with PFS or OS. Peri-necrotic CA IX localization correlated with PFS (Log rank =
      0.0181) and OS (Log rank p = 0.0015). All patients with a CA IX <= 5 % total area
      localization were alive at last follow-up. Perinecrotic CA IX staining was also
      associated with vascular proliferation (p = 0.006), though not with VEGF
      expression score. MIB-1 labeling index (LI) correlated with OS (HR 1.06, 95 % CI
      1.01, 1.12) and PFS (HR 1.08, 95 % CI 1.02, 1.14). MIB-1 LI and perinecrotic CA
      IX individually correlated with PFS. The effect of perinecrotic CA IX remained
      when grade was added to a Cox model predicting PFS. Immunodetection of CA IX and
      MIB-1 expression are predictive biomarkers for survival in children with
      posterior fossa ependymomas. These markers represent objective indicators of
      survival that supplement H&E grading alone.

PMID- 25563816
TI  - Salvage therapy with lomustine for temozolomide refractory recurrent anaplastic
      astrocytoma: a retrospective study.
AB  - There is no standard therapy for recurrent anaplastic astrocytoma (AA). Assess
      response and toxicity of lomustine (CCNU) in recurrent AA following prior
      surgery, radiotherapy and TMZ in a retrospective case series. Thirty-five adults
      (18 males; 17 females: median age 42.5 years) with TMZ refractory recurrent AA
      were treated with lomustine. Seven patients were treated at 1st recurrence and 28
      patients were treated at 2nd recurrence. Prior salvage therapy included re
      resection in 19, TMZ in 20 and radiotherapy in 7. A cycle of lomustine was
      defined as 110 mg/m(2) on day 1 only administered once every 6-8 weeks. Success
      of treatment was defined as progression free survival at 6 months of 40 % or
      better. Grade 3 or 4 toxicities included anemia (14 patients), constipation (1),
      fatigue (4), lymphopenia (5), nausea/vomiting (2), neutropenia (8) and
      thrombocytopenia (10). No grade five toxicities were seen. The median number of
      cycles of therapy was 3 (range 1-6). Best radiographic response was progressive
      disease in 14 (40 %), stable disease in 19 (54 %) and partial response in 2 (5.7
      %). Median progression free survival (PFS) was 4.5 months (range 1.5-12 months),
      6-month PFS was 40 % and 12 month PFS was 11.4 %. Median survival after onset of
      CCNU was 9.5 months (range 2.5-15 months). Median overall survival was 2.7 years
      (range 1.7-4.3). In this small retrospective series of patients with recurrent AA
      refractory to TMZ, lomustine appears to have modest single agent with manageable
      toxicity. Confirmation in a larger series of similar patients is required.

PMID- 25563817
TI  - Application of quality by design (QbD) approach to ultrasonic atomization spray
      coating of drug-eluting stents.
AB  - The drug coating process for coated drug-eluting stents (DES) has been identified
      as a key source of inter- and intra-batch variability in drug elution rates.
      Quality-by-design (QbD) principles were applied to gain an understanding of the
      ultrasonic spray coating process of DES. Statistically based design of
      experiments (DOE) were used to understand the relationship between ultrasonic
      atomization spray coating parameters and dependent variables such as coating mass
      ratio, roughness, drug solid state composite microstructure, and elution
      kinetics. Defect-free DES coatings composed of 70% 85:15 poly(DL-lactide-co
      glycolide) and 30% everolimus were fabricated with a constant coating mass. The
      drug elution profile was characterized by a mathematical model describing
      biphasic release kinetics. Model coefficients were analyzed as a DOE response.
      Changes in ultrasonic coating processing conditions resulted in substantial
      changes in roughness and elution kinetics. Based on the outcome from the DOE
      study, a design space was defined in terms of the critical coating process
      parameters resulting in optimum coating roughness and drug elution. This QbD
      methodology can be useful to enhance the quality of coated DES. 

PMID- 25563818
TI  - Telomere length in non-neoplastic gastric mucosa and its relationship to H.
      pylori infection, degree of gastritis, and NSAID use.
AB  - Telomere shortening occurs with human aging in many organs and tissues and is
      accelerated by rapid cell turnover and oxidative injury. We measured average
      telomere length using quantitative real-time PCR in non-neoplastic gastric mucosa
      and assessed its relationship to H. pylori-related gastritis, DNA methylation,
      ulcer disease, and nonsteroidal anti-inflammatory drug (NSAID) usage. Gastric
      biopsies were obtained from 151 cancer-free subjects including 49 chronic NSAID
      users and 102 nonusers. Relative telomere length in genomic DNA was measured by
      real-time PCR. H. pylori infection status, histological severity of gastritis,
      and serum pepsinogens (PGs) were also investigated. E-cadherin (CDH1) methylation
      status was determined by methylation-specific PCR (MSP). Average relative
      telomere length of H. pylori-infected subjects was significantly shortened when
      compared to H. pylori-negative subjects (p = 0.002) and was closely associated
      with all histological parameter of gastritis (all p values <0.01) and CDH1
      methylation (p = 0.0002). In H. pylori-negative subjects, NSAID users presented
      significantly shorter telomere length than nonusers (p = 0.028). Shorter telomere
      length was observed in duodenal and gastric ulcer patients compared with non
      ulcer subjects among NSAID users. Telomere shortening is closely associated with
      severity of H. pylori-induced gastritis and CDH1 methylation status. Also,
      telomere shortening is accelerated by NSAID usage especially in H. pylori
      negative subjects.

PMID- 25563820
TI  - To the editor.

PMID- 25563819
TI  - Long-term health-related quality of life of prostate cancer survivors varies by
      primary treatment. Results from the PiCTure (Prostate Cancer Treatment, your
      experience) study.
AB  - PURPOSE: Men are living longer with prostate cancer. In a two-country study, we
      investigated the health-related quality of life (HRQoL) of prostate cancer
      survivors up to 18 years post-diagnosis. METHODS: Postal questionnaires were
      administered in 2012 to 6559 prostate cancer (ICD10 C61) survivors 2-18 years
      post-diagnosis, identified through population-based cancer registries in Ireland.
      HRQoL was measured using QLQ-C30 and QLQ-PR25. HRQoL, functional and symptom
      scores were compared by primary treatment(s) using multiple linear regression.
      RESULTS: Fifty-four percent responded (n = 3348). After controlling for socio
      demographic and clinical factors, global HRQoL varied significantly by primary
      treatment (p < 0.001); compared to radical prostatectomy (RP), survivors who
      received androgen deprivation therapy alone (ADT; p < 0.001) or external beam
      radiotherapy (EBRT) without concurrent ADT (p = 0.001) had significantly lower
      global HRQoL. The global HRQoL of men who received brachytherapy (p = 0.157),
      EBRT with concurrent ADT (p = 0.940) or active surveillance/watchful waiting (p =
      0.388) was not significantly different from men treated with RP. There were
      statistically and clinically significant differences in general (fatigue, pain,
      dyspnoea, appetite loss, constipation, diarrhoea, financial difficulties) and
      disease-specific symptoms (sexual, urinary, bowel, ADT) by primary treatment.
      Fatigue and insomnia scores were high for survivors in all treatment groups.
      CONCLUSIONS: Prostate cancer survivors' long-term HRQoL varied with primary
      treatment. IMPLICATIONS OF CANCER SURVIVORS: Population-based information
      regarding statistically and clinically significant treatment effects on long-term
      global HRQoL, symptom burden and functionality should be provided during
      treatment decision-making. Screening for symptoms and utilising interventions
      during long-term follow-up may improve survivors' HRQoL.

PMID- 25563821
TI  - A novel mutation in the ABCA12 gene in a Turkish case of Harlequin ichthyosis.

PMID- 25563822
TI  - Learning to trust and trusting to learn: a theoretical framework.
AB  - Learning from other people requires integrating reasoning about an informant's
      psychological properties, such as knowledge and intent, with reasoning about the
      implications of the data the informant chooses to present. Here, we argue for an
      approach that considers these two reasoning paths as interrelated, reciprocal
      processes that develop over experience and guide learners when acquiring
      knowledge about the world.

PMID- 25563825
TI  - Affinity, stoichiometry and cooperativity of heterochromatin protein 1 (HP1)
      binding to nucleosomal arrays.
AB  - Heterochromatin protein 1 (HP1) participates in establishing and maintaining
      heterochromatin via its histone-modification-dependent chromatin interactions. In
      recent papers HP1 binding to nucleosomal arrays was measured in vitro and
      interpreted in terms of nearest-neighbour cooperative binding. This mode of
      chromatin interaction could lead to the spreading of HP1 along the nucleosome
      chain. Here, we reanalysed previous data by representing the nucleosome chain as
      a 1D binding lattice and showed how the experimental HP1 binding isotherms can be
      explained by a simpler model without cooperative interactions between neighboring
      HP1 dimers. Based on these calculations and spatial models of dinucleosomes and
      nucleosome chains, we propose that binding stoichiometry depends on the
      nucleosome repeat length (NRL) rather than protein interactions between HP1
      dimers. According to our calculations, more open nucleosome arrays with long DNA
      linkers are characterized by a larger number of binding sites in comparison to
      chains with a short NRL. Furthermore, we demonstrate by Monte Carlo simulations
      that the NRL dependent folding of the nucleosome chain can induce allosteric
      changes of HP1 binding sites. Thus, HP1 chromatin interactions can be modulated
      by the change of binding stoichiometry and the type of binding to condensed
      (methylated) and non-condensed (unmethylated) nucleosome arrays in the absence of
      direct interactions between HP1 dimers. 

PMID- 25563824
TI  - Chemotherapy with cytochalasin congeners in vitro and in vivo against murine
      models.
AB  - Background Despite inherent differences between the cytoskeletal networks of
      malignant and normal cells, and the clinical antineoplastic activity of
      microtubule-directed agents, there has yet to be a microfilament-directed agent
      approved for clinical use. One of the most studied microfilament-directed agents
      has been cytochalasin B, a mycogenic toxin known to disrupt the formation of
      actin polymers. Therefore, this study sought to expand on our previous work with
      the microfilament-directed agent, along with other less studied cytochalasin
      congeners. Materials and Methods We determined whether cytochalasin B exerted
      significant cytotoxic effects in vitro on adherent M109 lung carcinoma and B16BL6
      and B16F10 murine melanomas, or on suspension P388/ADR murine leukemia cells. We
      also examined whether cytochalasin B, its reduced congener 21, 22
      dihydrocytochalasin B (DiHCB), or cytochalasin D could synergize with doxorubicin
      (ADR) against ADR-resistant P388/ADR leukemia cells, and produce significant
      cytotoxicity in vitro. For in vivo characterization, cytochalasins B and D were
      administered intraperitoneally (i.p.) to Balb/c mice challenged with drug
      sensitive P388-S or multidrug resistant P388/ADR leukemias. Results Cytochalasin
      B demonstrated higher cytotoxicity against adherent lung carcinoma and melanoma
      cells than against suspension P388/ADR leukemia cells, as assessed by comparative
      effects on cell growth, and IC50 and IC80 values. Isobolographic analysis
      indicated that both cytochalasin B and DiHCB demonstrate considerable drug
      synergy with ADR against ADR-resistant P388/ADR leukemia, while cytochalasin D
      exhibits only additivity with ADR against the same cell line. In vivo,
      cytochalasins B and D substantially increased the life expectancy of mice
      challenged with P388/S and P388/ADR leukemias, and in some cases, produced long
      term survival. Conclusion Taken together, it appears that cytochalasins have
      unique antineoplastic activity that could potentiate a novel class of
      chemotherapeutic agents.

PMID- 25563827
TI  - Continuous positive airway pressure (CPAP) for acute bronchiolitis in children.
AB  - BACKGROUND: Acute bronchiolitis is one of the most frequent causes of emergency
      department visits and hospitalisation in infants. There is no specific treatment
      for bronchiolitis except for supportive therapy. Continuous positive airway
      pressure (CPAP) is supposed to widen the peripheral airways of the lung, allowing
      deflation of over-distended lungs in bronchiolitis. The increase in airway
      pressure also prevents the collapse of poorly supported peripheral small airways
      during expiration. In observational studies, CPAP is found to be beneficial in
      acute bronchiolitis. OBJECTIVES: To assess the efficacy and safety of CPAP
      compared to no CPAP or sham CPAP in infants and children up to three years of age
      with acute bronchiolitis. SEARCH METHODS: We searched CENTRAL (2014, Issue 3),
      MEDLINE (1946 to April week 2, 2014), EMBASE (1974 to April 2014), CINAHL (1981
      to April 2014) and LILACS (1982 to April 2014). SELECTION CRITERIA: We considered
      randomised controlled trials (RCTs), quasi-RCTS, cross-over RCTs and cluster-RCTs
      evaluating the effect of CPAP in children with acute bronchiolitis. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed study
      eligibility, extracted data using a structured proforma, analysed the data and
      performed meta-analyses. MAIN RESULTS: We included two studies with a total of 50
      participants under 12 months of age. In one study there was a high risk of bias
      for incomplete outcome data and selective reporting, and both studies had an
      unclear risk of bias for several domains including random sequence generation.
      The effect of CPAP on the need for mechanical ventilation in children with acute
      bronchiolitis was uncertain due to imprecision around the effect estimate (two
      RCTs, 50 participants; risk ratio (RR) 0.19, 95% CI 0.01 to 3.63; low quality
      evidence). Neither trial measured our other primary outcome of time to recovery.
      One trial found that CPAP significantly improved respiratory rate compared with
      no CPAP (one RCT, 19 participants; mean difference (MD) -5.70 breaths per minute,
      95% CI -9.30 to -2.10), although the other study reported no difference between
      groups with no numerical data to pool. Change in arterial oxygen saturation was
      measured in only one trial and the results were imprecise (one RCT, 19
      participants; MD -1.70%, 95% CI -3.76 to 0.36). The effect of CPAP on the change
      in partial pressure of carbon dioxide (pCO2) was also imprecise (two RCTs, 50
      participants; MD -2.62 mmHg, 95% CI -5.29 to 0.05; low quality evidence).
      Duration of hospital stay was similar in both of the groups (two RCTs, 50
      participants; MD 0.07 days, 95% CI -0.36 to 0.50; low quality evidence). Both
      trials reported no cases of pneumothorax and there were no deaths in either
      study. Change in partial pressure of oxygen (pO2), hospital admission rate (from
      emergency department to hospital), duration of emergency department stay, need
      for intensive care unit admission, local nasal effects and shock were not
      measured in either study. AUTHORS' CONCLUSIONS: The effect of CPAP in children
      with acute bronchiolitis is uncertain due to the limited evidence available.
      Larger trials with adequate power are needed to evaluate the effect of CPAP in
      children with acute bronchiolitis.

PMID- 25563826
TI  - Furosemide versus ethacrynic acid in pediatric patients undergoing cardiac
      surgery: a randomized controlled trial.
AB  - INTRODUCTION: Clinical effects of furosemide (F) and ethacrynic acid (EA)
      continuous infusion on urine output (UO), fluid balance, and renal, cardiac,
      respiratory, and metabolic function were compared in infants undergoing surgery
      for congenital heart diseases. METHODS: A prospective randomized double-blinded
      study was conducted. Patients received 0.2 mg/kg/h (up to 0.8 mg/kg/h) of either
      F or EA. RESULTS: In total, 38 patients were enrolled in the F group, and 36, in
      the EA group. No adverse reactions were recorded. UO at postoperative day (POD) 0
      was significantly higher in the EA group, 6.9 (3.3) ml/kg/h, compared with the F
      group, 4.6 (2.3) ml/kg/h (P = 0.002) but tended to be similar in the two groups
      thereafter. Mean administered F dose was 0.33 (0.19) mg/kg/h compared with 0.22
      (0.13) mg/kg/h of EA (P < 0.0001). Fluid balance was significantly more negative
      in the EA group at postoperative day 0: -43 (54) ml/kg/h versus -17 (32) ml/kg/h
      in the F group (P = 0.01). Serum creatinine, cystatin C and neutrophil gelatinase
      associated lipocalin levels and incidence of acute kidney injury did not show
      significant differences between groups. Metabolic alkalosis occurred frequently
      (about 70% of cases) in both groups, but mean bicarbonate level was higher in the
      EA group: 27.8 (1.5) M in the F group versus 29.1 (2) mM in the EA group (P =
      0.006). Mean cardiac index (CI) values were 2.6 (0.1) L/min/m(2) in the F group
      compared with 2.98 (0.09) L/min/m(2) in the EA group (P = 0.0081). Length of
      mechanical ventilation was shorter in the EA group, 5.5 (8.8) days compared with
      the F group, 6.7 (5.9) (P = 0.06). Length of Pediatric Cardiac Intensive Care
      Unit (PCICU) admission was shorter in the EA group: 14 (19) days compared with 16
      (15) in the F group (P = 0.046). CONCLUSIONS: In cardiac surgery infants, EA
      produced more UO compared with F on POD0. Generally, a smaller EA dose is
      required to achieve similar UO than F. EA and F were safe in terms of renal
      function, but EA caused a more-intense metabolic alkalosis. EA patients achieved
      better CI, and shorter mechanical ventilation and PCICU admission time. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01628731. Registered 24 June 2012.

PMID- 25563829
TI  - Erratum to: Sequential anaerobic/aerobic digestion for enhanced sludge
      stabilization: comparison of the process performance for mixed and waste sludge.

PMID- 25563828
TI  - Total mercury and methylmercury distributions in surface sediments from
      Kongsfjorden, Svalbard, Norwegian Arctic.
AB  - The total mercury (THg) and methylmercury (MeHg) distributions in the surface
      sediments of Kongsfjorden, Svalbard, in the Norwegian Arctic were investigated in
      this study. The results showed that THg concentrations ranged from 9.11 to 86.73
      ng g(-1), whereas MeHg concentrations had an average of only 0.11 ng g(-1).
      Factors that control the distribution and methylated transformation of mercury
      were examined, and the results suggested that the movements of ocean currents and
      glaciers affect the THg distribution. The total organic carbon (TOC) and N
      contents in the sediments were positively correlated with THg concentration,
      which indicated that the THg distribution at these stations was primarily
      controlled by organic matter in the sediments. A complex relationship was
      observed between the THg and S contents, possibly due to anthropogenic activities
      involved in the perennial scientific expedition. MeHg and THg exhibited similar
      correlations with the sediment chemical characteristics for all stations
      suggesting that MeHg may be produced locally through the microbial methylation of
      mercury. 

PMID- 25563830
TI  - Macrophyta as a vector of contemporary and historical mercury from the marine
      environment to the trophic web.
AB  - Macrophyta are the initial link introducing toxic mercury to the trophic chain.
      Research was carried out at 24 stations located within the Polish coastal zone of
      the Southern Baltic, in the years 2006-2012. Fifteen taxa were collected,
      belonging to four phyla: green algae (Chlorophyta), brown algae (Phaeophyta), red
      algae (Rhodophyta) and flowering vascular plants (Angiospermophyta), and total
      mercury concentrations were ascertained. The urbanisation of the coastal zone has
      influenced the rise in Hg concentrations in macroalgae, and the inflow of
      contaminants from the river drainage area has contributed to an increase in metal
      concentration in vascular plants. At the outlets of rivers possessing the largest
      drainage areas in the Baltic (the Vistula and the Oder), no increases in mercury
      concentration were observed in macrophyta. Increase in environmental quality and
      a prolonged vegetative season results in the growing coverage of algae on the
      seabed and in consequence leads to rapid introduction of contemporary mercury and
      Hg deposited to sediments over the past decades into the trophic chain. Thriving
      phytobenthos was found to affect faster integration of Hg into the trophic web. 

PMID- 25563832
TI  - Impact of fine particulate fluctuation and other variables on Beijing's air
      quality index.
AB  - We analyzed fluctuation in Beijing's air quality over 328 days, based on air
      quality grades and air quality data from 35 atmospheric monitoring stations. Our
      results show the air over Beijing is subject to pollution 152 days of the year,
      or 46.34%. Among all pollutants, fine particulates, solid or liquid, 2.5 MUm or
      less in size (PM2.5), appeared most frequently as the primary pollutant: 249
      days, or 76% of the sample year (328 days). Nitrogen dioxide (NO2) and coarse
      particulates (PM10) cause the least pollution, appearing only 7 and 3 days, or 2
      and 1% of the sample year, respectively. In Beijing, fine particulates like PM2.5
      vary seasonally: 154.54 +/- 18.60 in winter > 145.22 +/- 18.61 in spring > 140.16
      +/- 20.76 in autumn > 122.37 +/- 13.42 in summer. Air quality is best in August
      and worst in December, while various districts in Beijing experience different
      air quality. To be specific, from south to north and from west to east, air
      quality tends to improve. Meteorological elements have a constraining effect on
      air pollutants, which means there is a linear correlation between the air quality
      index and humidity, rainfall, wind speed, and temperature. Under a typical
      pollution scenario, the higher the air quality index (AQI) value, the lower the
      wind speed and the greater the relative humidity; the lower the AQI value, the
      higher the wind speed and lower the relative humidity. Analysis of influencing
      factors reveals that the air pollution is mainly particulate matter produced by
      burning coal, vehicle emissions, volatile oils and gas, fast development of food
      services, emissions from the surrounding region, and natural dust clouds formed
      in arid areas to the northwest. Topography affects the distribution of
      meteorological conditions, in turn varying air quality over the region from one
      location to another. Human activities also exercise impact on urban air quality
      with dual functions.

PMID- 25563831
TI  - Comparative proteomics exploring the molecular mechanism of eutrophic water
      purification using water hyacinth (Eichhornia crassipes).
AB  - Eutrophication is a serious threat to ecosystem stability and use of water
      resources worldwide. Accordingly, physical, chemical, and biological technologies
      have been developed to treat eutrophic water. Phytoremediation has attracted a
      great deal of attention, and water hyacinth (Eichhornia crassipes) is regarded as
      one of the best plants for purification of eutrophic water. Previous studies have
      shown that water hyacinths remove nitrogen (N) and phosphorus (P) via diverse
      processes and that they can inhibit the growth of algae. However, the molecular
      mechanisms responsible for these processes, especially the role of proteins, are
      unknown. In this study, we applied a proteomics approach to investigate the
      protein dynamics of water hyacinth under three eutrophication levels. The results
      suggested that proteins with various functions, including response to stress, N
      and P metabolic pathways, synthesis and secretion, photosynthesis, biosynthesis,
      and energy metabolism, were involved in regulating water hyacinth to endure the
      excess-nutrient environment, remove N and P, and inhibit algal growth. The
      results help us understand the mechanism of purification of eutrophic water by
      water hyacinth and supply a theoretical basis for improving techniques for
      phytoremediation of polluted water. 

PMID- 25563833
TI  - Temporal dynamics of the cellular events in tobacco leaves exposed in Sao Paulo,
      Brazil, indicate oxidative stress by ozone.
AB  - Nicotiana tabacum 'Bel-W3' is widely used as an ozone bioindicator species,
      showing typical necrosis preceded by microscopic markers of oxidative stress.
      This study aimed to follow the development of symptoms in tobacco exposed in Sao
      Paulo highlighting the temporal dynamics of the cellular events. Leaves with and
      without necrosis were processed according to standard techniques for anatomical
      analyses. Leaves from the site with higher SUM00 presented thinner palisade
      parenchyma, fewer layers of spongy parenchyma, higher stomatal density, clusters
      of vessel elements in the midrib, erosion of cuticular waxes and stomatal damage.
      The sequence of microscopic events from the third day of exposure were
      condensation of the cytoplasm in parenchyma tissue, sinuosity of anticlinal
      walls, pectinaceous cell wall protrusions, chromatin condensation and changes in
      chlorophyll autofluorescence. On the 14th day of exposure, these events finally
      led to cell death in the palisade parenchyma and necrosis on the leaf. The
      markers observed indicated oxidative stress caused by ozone.

PMID- 25563834
TI  - Distribution and chemical forms of copper in the root cells of castor seedlings
      and their tolerance to copper phytotoxicity in hydroponic culture.
AB  - The subcellular localization and chemical forms of copper in castor (Ricinus
      communis L.) seedlings grown in hydroponic nutrient solution were identified by
      chemical extraction, transmission electron microscopy, and Fourier transform
      infrared spectroscopy. The wild castor seeds were harvested from an abandoned
      copper mine in Tonglu Mountain, Daye City of Hubei Province, China. The results
      revealed that (1) the seedlings grew naturally in MS liquid medium with 40.00 mg
      kg(-1) CuSO4, in which the seedling growth rate and biomass index were 0.14 and
      1.23, respectively, which were the highest values among all the treatments. The
      copper content in castor seedlings increased along with elevated CuSO4
      concentration in the medium, reaching a maximum value of 16 570.12 mg kg(-1)(DW)
      when exposed to 60.00 mg L(-1) CuSO4, where 91.31% of the copper was accumulated
      in roots. (2) The copper existed in various chemical forms in the roots of the
      castor seedlings. Copper of 67.66% was extracted from the components of cell
      walls, such as exchangeable acidic polar compounds, cellulose and lignin, protein
      and pectin, and less concentrated in cell cytoplasm and nuclei. (3) Furthermore,
      the root cell walls were thickened when the castor seedlings exposed to CuSO4,
      with a large amount of high-density electron bodies, attached to the thickened
      cell walls. In the cell walls, most copper was bound to the carboxyl (-COOH) and
      hydroxyl (-OH) groups of acidic polar compounds, cellulose, hemicellulose, and
      polysaccharides. The conclusion showed that castor exhibited a strong tolerance
      to copper, the copper were accumulated mainly in the root cell, the root cell
      walls of castor were the major location of patience and detoxification in copper
      stress.

PMID- 25563835
TI  - Antibiotic resistance pattern and gene expression of non-typhoid Salmonella in
      riversheds.
AB  - In this study, antibiotic resistance and major phenol and genotypes of non
      typhoid Salmonella spp. from riversheds in Taiwan were examined. In 236 water
      samples tested, 54 (22.9%) contained Salmonella spp. Fifteen Salmonella serovars
      were identified from the Salmonella isolates, and some common serovars are
      associated with infections of human and livestock, including Albany (27.8%),
      Newport (14.8%), Bareilly (13.0%), Derby (11.1%), and Typhimurium (7.4%). Various
      environmental factors may also affect the presence and proportion of different
      serovars in the receiving waters. In contrast, serovars with narrower range of
      hosts, e.g., Dublin, were rarely detected. The Salmonella isolates were subjected
      to eight antibiotics for drug resistance, and 51.9% of the samples were resistant
      to at least one tested antibiotics. Tetracycline and sulfadiazine were the two
      most ineffective antibiotics against the Salmonella isolates, and the results
      were indicative of long-term antibiotics abuse as fodder supplements in animal
      husbandry. The more commonly detected serovars such as Albany, Derby, and
      Typhimurium were also more likely to be resistant to multiple antibiotics.
      Finally, a significant correlation was observed between resistance to
      chloramphenicol and the resistance gene cmlA, suggesting that the resistance
      genotypes could persist in the environment even long after prohibition of the
      drug use. The high prevalence of antibiotic-resistant Salmonella spp. infers
      elevated infection risks that must be further examined.

PMID- 25563836
TI  - A transporter for abiotic stress and plant metabolite resistance in the
      ectomycorrhizal fungus Tricholoma vaccinum.
AB  - Fungi exposed to toxic substances including heavy metals, xenobiotics, or
      secondary metabolites formed by co-occurring plants or other microorganisms
      require a detoxification system provided by exporters of several classes of
      transmembrane proteins. In case of mycorrhiza, plant metabolites need to be
      exported at the plant interface, while the extraradical hyphae may prevent heavy
      metal uptake, thus acting as a biofilter to the host plant at high environmental
      concentrations. One major family of such transporter proteins is the multidrug
      and toxic compound extrusion (MATE) class, a member of which, Mte1, was studied
      in the ectomycorrhizal fungus Tricholoma vaccinum. Phylogenetic analyses placed
      the protein in a subgroup of basidiomycete MATE sequences. The gene mte1 was
      found to be induced during symbiotic interaction. It mediated detoxification of
      xenobiotics and metal ions such as Cu, Li, Al, and Ni, as well as secondary plant
      metabolites if heterologously expressed in Saccharomyces cerevisiae. 

PMID- 25563837
TI  - Hydroacoustic and spatial analysis of sediment fluxes and accumulation rates in
      two Virginia reservoirs, USA.
AB  - Watershed sediment fluxes and reservoir sediment accumulation rates were analyzed
      in two contrasting reservoir systems in central and western Virginia. Lake
      Pelham, located in the Piedmont geologic province, is a human-impacted reservoir
      with a watershed dominated by agricultural, residential and industrial land uses.
      Conversely, Lake Moomaw has a largely undeveloped watershed characterized by very
      steep slopes and forested land use located in the Valley and Ridge province. The
      Revised Universal Soil Loss Equation (RUSLE) and sediment delivery ratios (SDRs)
      were used to estimate soil losses in the two watersheds. Bathymetric and sediment
      accumulation surveys of the two reservoirs were also conducted using a multi
      frequency hydroacoustic surveying system. The RUSLE/SDR erosion model estimates
      2150 kg ha(-1) year(-1) for Lake Pelham and 2720 kg ha(-1) year(-1) for Lake
      Moomaw, a 410 and 13 % increase from assumed pristine (100 % forested) land use
      for the respective basins. Mean sediment accumulation rates of 1.51 and 0.60 cm
      year(-1) were estimated from the hydroacoustic survey of Lake Pelham and Lake
      Moomaw, respectively. Overall, Lake Moomaw has relatively low sediment
      accumulation rates; however, the reservoir is vulnerable to increases in sediment
      fluxes with further human development due to the steep slopes and highly erodible
      colluvial soils that characterize the basin. Higher erosion and sediment
      accumulation rates in Lake Pelham are most likely reflecting the impact of human
      development on sedimentation processes, where the loss of vegetal buffers and
      increase in impervious surfaces exacerbates both the surficial soil losses as
      well as intrinsic stream sediment production leading to the current annual
      reservoir capacity loss of 0.4 %. 

PMID- 25563838
TI  - Transdiagnostic factors of psychopathology and substance use disorders: a review.
AB  - PURPOSE: Research on the structure of mental disorders and comorbidity indicates
      that many forms of psychopathology and substance use disorders are manifestations
      of relatively few transdiagnostic latent factors. These factors have important
      consequences for mental disorder research and applied practice. METHODS: We
      provide an overview of the transdiagnostic factor literature, with particular
      focus on recent advances. RESULTS: Internalizing and externalizing
      transdiagnostic factors have been well characterized in terms of their
      structures, links with disorders, stability, and statistical properties (e.g.,
      invariance and distributions). Research on additional transdiagnostic factors,
      such as thought disorder, is quickly advancing latent structural models, as are
      integrations of transdiagnostic constructs with personality traits. Genetically
      informed analyses continue to clarify the origins of transdiagnostic factor
      levels, and links between these factors and important environmental exposures
      provide promising new avenues of inquiry. CONCLUSIONS: Transdiagnostic factors
      account for the development and continuity of disorders and comorbidity over
      time, function as the primary links between disorders and important outcomes such
      as suicide, mediate associations between environmental exposures and disorders,
      provide an empirically supported classification system, and serve as foci for
      efficient, broadband intervention approaches. Overall, transdiagnostic factor
      research indicates the paramount importance of understanding these constructs
      and, thereby, broadening our understanding of mental disorder in general.

PMID- 25563839
TI  - Adventitial CXCL1/G-CSF expression in response to acute aortic dissection
      triggers local neutrophil recruitment and activation leading to aortic rupture.
AB  - RATIONALE: In-hospital outcomes are generally acceptable in patients with type B
      dissection; however, some patients present with undesirable complications, such
      as aortic expansion and rupture. Excessive inflammation is an independent
      predictor of adverse clinical outcomes. OBJECTIVE: We have investigated the
      underlying mechanisms of catastrophic complications after acute aortic dissection
      (AAD) in mice. METHODS AND RESULTS: When angiotensin II was administered in lysyl
      oxidase inhibitor-preconditioned mice, AAD emerged within 24 hours. The
      dissection was initiated at the proximal site of the descending thoracic aorta
      and propagated distally into an abdominal site. Dissection of the aorta caused
      dilatation, and ~70% of the mice died of aortic rupture. AAD triggered CXCL1 and
      granulocyte-colony stimulating factor expression in the tunica adventitia of the
      dissected aorta, leading to elevation of circulating CXCL1/granulocyte-colony
      stimulating factor levels. Bone marrow CXCL12 was reduced. These chemokine
      changes facilitated neutrophil egress from bone marrow and infiltration into the
      aortic adventitia. Interference of CXCL1 function using an anti-CXCR2 antibody
      reduced neutrophil accumulation and limited aortic rupture post AAD. The tunica
      adventitia of the expanded dissected aorta demonstrated high levels of
      interleukin-6 (IL-6) expression. Neutrophils were the major sources of IL-6, and
      CXCR2 neutralization significantly reduced local and systemic levels of IL-6.
      Furthermore, disruption of IL-6 effectively suppressed dilatation and rupture of
      the dissected aorta without any influence on the incidence of AAD and neutrophil
      mobilization. CONCLUSIONS: Adventitial CXCL1/granulocyte-colony stimulating
      factor expression in response to AAD triggers local neutrophil recruitment and
      activation. This leads to adventitial inflammation via IL-6 and results in aortic
      expansion and rupture.

PMID- 25563841
TI  - Androgen receptor actions modify skin structure and chemical carcinogen-induced
      skin cancer susceptibility in mice.
AB  - Men are significantly more susceptible to non-melanoma skin cancers than women,
      and the androgen receptor (AR) is widely distributed in the skin, suggesting a
      ro?le for androgens acting via AR. Therefore, we explored the role of androgen
      action via AR in susceptibility to experimental 7,12-dimethylbenz[a]anthracene
      (DMBA)-induced skin carcinogenesis and in skin structural development of male and
      female mice. We demonstrate that both the male gender and androgen action via AR
      modify the susceptibility to carcinogen-induced skin cancer, but the effect
      depends on the carcinogenesis model used. Following systemic DMBA exposure, males
      were significantly (p < 0.05) more susceptible to DMBA-induced experimental skin
      cancer than females and AR inactivation significantly delayed cancer detection in
      both male (median time to palpable tumours 19 vs. >35 weeks (wild-type [WT] vs.
      AR knockout [ARKO], p < 0.001) and female (27 vs. >35 weeks, p = 0.008)) mice. In
      contrast, following DMBA/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      multistage local skin carcinogenesis, AR inactivation protected against formation
      of DMBA-induced skin cancers in both male and female mice. The skin structure was
      also affected by gender effect as well as the AR inactivation and could at least
      partly explain the different responses between the carcinogenesis models
      (systemic vs. topical). In addition, AR inactivation modified Cox-1 and Cox-2
      expression in the skin, suggesting possible molecular mechanism for the AR effect
      on skin. Finally, some gender differences are observed also in ARKO mice
      insensitive to androgens, suggesting that factors other than androgens also play
      a role in gender-dependent skin carcinogenesis.

PMID- 25563842
TI  - The midgut of the silkmoth Bombyx mori is able to recycle molecules derived from
      degeneration of the larval midgut epithelium.
AB  - The midgut represents the middle part of the alimentary canal and is responsible
      for nutrient digestion and absorption in insect larva. Despite the growing
      interest in this organ for different purposes, such as studies on morphogenesis
      and differentiation, stem cell biology, cell death processes and transport
      mechanisms, basic information on midgut development is still lacking for a large
      proportion of insect species. Undoubtedly, this lack of data could hinder the
      full exploitation of practical applications that involve midgut as their primary
      target. This may represent in particular a significant problem for Lepidoptera,
      an insect order that includes some of the most important species of high economic
      importance. With the aim of overcoming this fragmentation of knowledge, we
      performed a detailed morphofunctional analysis of the midgut of the silkworm,
      Bombyx mori, a representative model among Lepidoptera, during its development
      from the larval up to the adult stage, focusing attention on stem cells. Our data
      demonstrate stem cell proliferation and differentiation, not only in the larval
      midgut but also in the pupal and adult midgut epithelium. Moreover, we present
      evidence for a complex trophic relationship between the dying larval epithelium
      and the new adult one, which is established during metamorphosis. This study,
      besides representing the first morphological and functional characterization of
      the changes that occur in the midgut of a lepidopteron during the transition from
      the larva to the moth, provides a detailed analysis of the midgut of the adult
      insect, a stage that has been neglected up to now. 

PMID- 25563840
TI  - Receptor-interacting protein kinase 3 contributes to abdominal aortic aneurysms
      via smooth muscle cell necrosis and inflammation.
AB  - RATIONALE: Depletion of medial smooth muscle cell (SMC) is a major pathological
      characteristic of abdominal aortic aneurysm (AAA), although the mechanism by
      which these cells are eliminated remains incompletely understood. We reasoned
      that necroptosis, a recently described form of necrosis mediated by receptor
      interacting protein kinase 3 (RIP3), may contribute to AAA pathology through the
      induction of SMC death and the significant production of inflammatory cytokines.
      OBJECTIVE: To test the hypothesis that RIP3-mediated necroptosis is actively
      involved in aneurysm pathogenesis. METHODS AND RESULTS: RIP3 and RIP1 levels were
      found to be elevated in human AAAs, most noticeably in SMCs. Elevations of RIP3
      and SMC necrosis were also observed in the elastase-induced mouse model of AAAs.
      Deletion of one or both copies of Rip3 prevented AAA formation. By transplanting
      Rip3(+/-) aortae to Rip3(+/+) mice, we demonstrated that reduced Rip3 expression
      in arterial wall was the primary cause of aneurysm resistance. In vitro,
      adenoviral overexpression of RIP3 was sufficient to trigger SMC necroptosis.
      Protein kinase C-delta contributed to tumor necrosis factor-alpha-induced SMC
      necroptosis by regulating Rip3 expression. Furthermore, Rip3 deficiency impaired
      tumor necrosis factor-alpha-induced inflammatory gene expression in aortic SMCs,
      which was at least in part because of attenuation of p65 Ser536 phosphorylation.
      In vivo, the lack of RIP3 diminished activation of p65 in SMCs, implicating a
      necrosis independent function of RIP3 in aneurysms. CONCLUSIONS: Enhanced RIP3
      signaling in aneurysmal tissues contributes to AAA progression by causing SMC
      necroptosis, as well as stimulating vascular inflammation, and therefore may
      serve as a novel therapeutic target for AAA treatment.

PMID- 25563843
TI  - Electrochemical performance and carbon deposition resistance of M
      BaZr0.1Ce0.7Y0.1Yb0.1O3-delta (M = Pd, Cu, Ni or NiCu) anodes for solid oxide
      fuel cells.
AB  - Pd-, Cu-, Ni- and NiCu-BaZr0.1Ce0.7Y0.1Yb0.1O3-delta anodes, designated as M
      BZCYYb, were prepared by impregnating M-containing solution into BZCYYb scaffold,
      and investigated in the aspects of electrocatalytic activity for the reactions of
      H2 and CH4 oxidation and the resistance to carbon deposition. Impregnation of Pd,
      Ni or NiCu significantly reduced both the ohmic (ROmega) and polarization (RP)
      losses of BZCYYb anode exposed to H2 or CH4, while Cu impregnation decreased only
      ROmega in H2 and the both in CH4. Pd-, Ni- and NiCu-BZCYYb anodes were resistant
      to carbon deposition in wet (3 mol. % H2O) CH4 at 750 degrees C. Deposited carbon
      fibers were observed in Pd- and Ni-BZCYYb anodes exposed to dry CH4 at 750
      degrees C for 12 h, and not observed in NiCu-BZCYYb exposed to dry CH4 at 750
      degrees C for 24 h. The performance of a full cell with NiCu-BZCYYb anode, YSZ
      electrolyte and La0.6Sr0.4Co0.2Fe0.8O3-delta-Gd doped CeO2 (LSCF-GDC) cathode was
      stable at 750 degrees C in wet CH4 for 130 h, indicating that NiCu-BZCYYb is a
      promising anode for direct CH4 solid oxide fuel cells (SOFCs).

PMID- 25563844
TI  - Diversity in the Toll-like receptor genes of the Tasmanian devil (Sarcophilus
      harrisii).
AB  - The Tasmanian devil is an endangered marsupial species that has survived several
      historical bottlenecks and now has low genetic diversity. Here we characterize
      the Toll-like receptor (TLR) genes and their diversity in the Tasmanian devil.
      TLRs are a key innate immune gene family found in all animals. Ten TLR genes were
      identified in the Tasmanian devil genome. Unusually low levels of diversity were
      found in 25 devils from across Tasmania. We found two alleles at TLR2, TLR3 and
      TLR6. The other seven genes were monomorphic. The insurance population, which
      safeguards the species from extinction, has successfully managed to capture all
      of these TLR alleles, but concerns remain for the long-term survival of this
      species. 

PMID- 25563845
TI  - Binding modes of a core-extended metalloporphyrin to human telomeric DNA G
      quadruplexes.
AB  - The molecular recognition of human telomeric G-quadruplexes by a novel cationic
      pi-extended Ni(II)-porphyrin (Ni(II)-TImidP4) is studied in aqueous solutions via
      (chir)optical spectroscopy, Fluorescence Resonance Energy Transfer (FRET) melting
      assay, and computational molecular modeling. The results are systematically
      compared with the recognition by a conventional meso-substituted Ni(II)-porphyrin
      (Ni(II)-TMPyP4), which allows us to pinpoint the differences in binding modes
      depending on the G-quadruplex topology. Importantly, FRET melting assays show the
      higher selectivity of Ni(II)-TImidP4 towards human telomeric G4 than that of
      Ni(II)-TMPyP4. 

PMID- 25563850
TI  - Editorial: Personalized cancer treatment.

PMID- 25563847
TI  - Switching and withdrawing hormonal agents for castration-resistant prostate
      cancer.
AB  - The antiandrogen withdrawal syndrome (AAWS) is characterized by tumour regression
      and a decline in serum PSA on discontinuation of antiandrogen therapy in patients
      with prostate cancer. This phenomenon has been best described with the withdrawal
      of the nonsteroidal antiandrogens, bicalutamide and flutamide, but has also been
      reported with a wide range of hormonal agents. Mutations that occur in advanced
      prostate cancer and induce partial activation of the androgen receptor (AR) by
      hormonal agents have been suggested as the main causal mechanism of the AAWS.
      Corticosteroids, used singly or in conjunction with abiraterone, docetaxel and
      cabazitaxel might also be associated with the AAWS. The discovery of the
      Phe876Leu mutation in the AR, which is activated by enzalutamide, raises the
      possibility of withdrawal responses to novel hormonal agents. This Review
      focusses on the molecular mechanisms responsible for withdrawal responses, the
      role of AR mutations in the development of treatment resistance, and the evidence
      for the sequential use of antiandrogens in prostate cancer therapy. The
      implications of AR mutations for the development of novel drugs that target the
      AR are discussed, as are the challenges associated with redefining the utility of
      older treatments in the current therapeutic landscape.

PMID- 25563848
TI  - Testosterone therapy and prostate cancer--safety concerns are well founded.
AB  - Testosterone is a potent hormone with a variety of physiological effects. The
      diagnosis of androgen deficiency has increased dramatically over the past decade,
      along with the widespread use of testosterone supplementation therapy (TST). The
      long-term effects of TST are uncertain, and the risk of overdiagnosis and
      overtreatment of men who have a normal age-related decline in testosterone is
      substantial. The biology of the androgen receptor (AR) pathway is complex, and
      the saturation model does not take the heterogeneity of human prostate cancer
      into account. Large-scale trials to confirm the safety of testosterone with
      respect to the risks of prostate cancer and cardiovascular disease with
      reasonable confidence limits have not been done, and existing data are
      insufficient to exclude these adverse events. Instead, evidence suggests that
      prostate cancer could, in fact, be stimulated by TST, and that the risk of
      cardiovascular events is increased. Overall, TST seems to impose significant
      risks, and should be used with caution.

PMID- 25563849
TI  - Insights into the species-specific TLR4 signaling mechanism in response to
      Rhodobacter sphaeroides lipid A detection.
AB  - TLR4 in complex with MD2 senses the presence of lipid A (LA) and initiates a
      signaling cascade that curb the infection. This complex is evolutionarily
      conserved and can initiate the immune system in response to a variety of LAs. In
      this study, molecular dynamics simulation (25 ns) was performed to elucidate the
      differential behavior of TLR4/MD2 complex in response to Rhodobacter sphaeroides
      lipid A (RsLA). Penta-acyl chain-containing RsLA is at the verge of agonist (6
      acyl-chains) and antagonist (4 acyl-chains) structure, and activates the TLR4
      pathway in horses and hamsters, while inhibiting in humans and murine. In the
      time-evolved coordinates, the promising factors that dictated the differential
      response included the local and global mobility pattern of complexes, solvent
      accessible surface area of ligand, and surface charge distributions of TLR4 and
      MD2. We showed that the GlcN1-GlcN2 backbone acquires agonist (3FXI)-like
      configurations in horses and hamsters, while acquiring antagonist (2E59)-like
      configurations in humans and murine systems. Moreover, analysis of F126 behavior
      in the MD2 F126 loop (amino acids 123-129) and loop EF (81-89) suggested that
      certain sequence variations also contribute to species-specific response. This
      study underlines the TLR4 signaling mechanism and provides new therapeutic
      opportunities. 

PMID- 25563851
TI  - Molecular testing and personalized treatment of lung cancer.
AB  - Lung malignancy is a leading cause of cancer related morbidity and mortality
      worldwide. The majority (85%) of cases are histologically proven non-small cell
      lung carcinomas (NSCLC). More than 55% of lung carcinomas harbor at least one
      genetic alteration, most of them being histologic subtype specific. This review
      summarizes the progress in personalized care of lung cancer by reviewing the
      literature on EGFR, ALK and KRAS molecular alterations, currently used in
      clinical practice, to direct the decision making process for lung cancer therapy.
      In addition, we will discuss some recently characterized molecular alterations
      whose targeting is being tested in clinical trials and holds promise for future
      therapeutic targeting. The role of minimally invasive procedures in lung cancer
      diagnosis and staging is also discussed as these techniques now play a central
      role in lung cancer management by providing the bulk of material for modern
      molecular diagnostics. 

PMID- 25563852
TI  - Current therapeutic leads for the treatment of melanoma: targeted immunotherapy
      in the post-genomic era.
AB  - Metastatic melanoma has a poor prognosis and until today most therapeutic
      approaches are ineffective. Advances in molecular pathology and genome analysis
      technologies have led to the identification of genetic events and immune
      regulatory checkpoints that provide novel targets for pharmaceutical intervention
      in melanoma. Development of selective mitogen-activated kinase (MAPK) pathway
      inhibitors was the first major achievement coming from genetic studies that
      identified a constitutively active MAP kinase pathway and BRAF activating
      mutations in melanoma. At the same time, the manipulation of immune system
      checkpoints through monoclonal antibodies changed clinical practice and led to
      further improvement of patient outcomes. In an effort to further develop melanoma
      targeted therapies that depend on the genetic profile of a given patient, high
      throughput genome wide approaches (next-generation sequencing [NGS], gene arrays,
      etc) have been employed for the characterization of genetic alterations in the
      patient's tumor. In the near future, the combined information from the genetic
      and immune background of an individual will provide the basis for a personalized,
      highly targeted approach in the treatment of melanoma. 

PMID- 25563853
TI  - Targeted pathways in breast cancer: molecular and protein markers guiding
      therapeutic decisions.
AB  - Breast carcinoma is currently considered as a group of diseases, differing not
      only in histopathologic phenotype, as indicated by histologic type and grade, but
      also in their protein, genetic and epigenetic molecular profile. The standard of
      care indicates that the core information for patient management includes data on
      Estrogen Receptor (ER), Progesterone Receptor (PgR) and Human Epidermal Growth
      Factor Receptor 2 (HER2), while there is an emerging role for the proliferation
      marker Ki67. These indices can be provided even in low resource settings and are
      indispensable for prognostication and therapeutic patient management. With the
      progress in molecular and translational research, there is a growing body of
      information on the molecular subtypes of breast carcinoma and their significance,
      and multigene signature assays are used to dictate prognosis and guide
      therapeutics in high resource settings. In addition, several cellular pathways
      involved in tumor growth and spread are dissected and targeted in clinical
      trials. Among these are the p53, RB, PI3K/Akt/mTOR and Ras/MAPK pathways,
      alterations associated with genetic instability and epigenetic alterations
      including histone methylation and acetylation, DNA methylation and microRNAs
      expression. The tumor immune microenvironment, including the tumor infiltrating
      lymphocytes (TILs) is attracting significant research interest. This review
      summarizes the mechanisms of function of the above factors in breast
      tumorigenesis with emphasis on their prognostic and predictive value and their
      use as therapeutic targets. 

PMID- 25563854
TI  - Towards dipyrrins: oxidation and metalation of acyclic and macrocyclic Schiff
      base dipyrromethanes.
AB  - Oxidation of acyclic Schiff-base dipyrromethanes cleanly results in dipyrrins,
      whereas the macrocyclic 'Pacman' analogues either decompose or form new dinuclear
      copper(ii) complexes that are inert to ligand oxidation; the unhindered hydrogen
      substituent at the meso-carbon allows new structural motifs to form. 

PMID- 25563856
TI  - Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways.
AB  - Innate immunity, which is the first line of host defense against invading
      microbial pathogens in multicellular organisms, occurs through germline-encoded
      pattern-recognition receptors. The Toll-like receptor/Interleukin (IL)-1 receptor
      (TLR/IL-1R) superfamily comprises proteins that contain the phylogenetically
      conserved Toll/IL-1 receptor (TIR) domain, which is responsible for the
      propagation of downstream signaling through recruitment of TIR domain containing
      cytosolic adaptor proteins such as MyD88, TIRAP/MAL, TRIF, TRAM and SARM. These
      interactions activate transcription factors that regulate the expression of
      various proinflammatory cytokines (IL-1, IL-6, IL-8 and TNF-alpha) and
      chemokines. Activation of the TLR/IL-1R signaling pathway promotes the onset of
      inflammatory diseases, autoimmune diseases and cancer; therefore, this pathway
      can be used for the development of therapeutic strategies against these types of
      pathogenesis. In this review paper, we illustrate the role of the TIR-TIR domain
      interaction with the TLR/IL-1R signaling pathway in inflammation and apoptosis
      and recent therapeutic drugs targeted to inhibit the downstream signaling cascade
      for treatment of inflammatory diseases and cancer. 

PMID- 25563857
TI  - Cardiovascular Risk Factors in Chronic Inflammatory Rheumatic Diseases: Modern
      Assessment and Diagnosis.
AB  - The current view is that systemic inflammation, which is specific to all chronic
      inflammatory rheumatic diseases (CIRD), accelerates atherogenesis; this
      hypothesis is supported by the high cardiovascular (CV) morbidity and mortality
      rates and the high prevalence of all atherosclerosis stages and complications in
      CIRD patients. The assessment of traditional CV risk factors underestimates the
      actual risk in patients with CIRD. A comprehensive evaluation and follow-up of
      both traditional and non-traditional CV risk factors, as well as the correct
      classification of risk reduction categories are necessary. Imaging techniques
      (e.g. carotid intima-media thickness and flow-mediated vasodilation) can be used
      for the early diagnosis of endothelial dysfunction. Immunologic and metabolic
      markers (anti-cyclic citrullinated peptide (CCP) antibodies, IgM rheumatoid
      factor, circulating immune complexes, proinflammatory cytokines, TH0/TH1
      lymphocytes and homocysteine) may be involved in the atherosclerotic disease
      development specific to CIRD. A modern therapeutic approach should include the
      early diagnosis of endothelial dysfunction and atherosclerosis, treatment of
      CIRD, specific medication designed to control atherosclerosis, changes in patient
      lifestyle and periodic follow-ups. The assessment and diagnosis of traditional
      and non-traditional CV risk factors, followed by aggressive prevention and
      therapy, are necessary to achieve efficient control over the inflammation,
      immunologic and metabolic disorders specific to CIRD. 

PMID- 25563859
TI  - Post metalation of solvothermally grown electroactive porphyrin metal-organic
      framework thin films.
AB  - Uniform thin films of a metal-organic framework, which is constructed from free
      base porphyrin linkers and hexa-zirconium nodes (MOF-525), are solvothermally
      grown on conducting substrates. Subsequently, solvothermal post metalations are
      employed to prepare the Zn-MOF-525 and Co-MOF-525 thin films. All the thin films
      are electroactive in aqueous media. 

PMID- 25563855
TI  - Determinants of eosinophil survival and apoptotic cell death.
AB  - Eosinophils (Eos) are potent inflammatory cells and abundantly present in the
      sputum and lung of patients with allergic asthma. During both transit to and
      residence in the lung, Eos contact prosurvival cytokines, particularly IL-3, IL-5
      and GM-CSF, that attenuate cell death. Cytokine signaling modulates the
      expression and function of a number of intracellular pro- and anti-apoptotic
      molecules. Both intrinsic mitochondrial and extrinsic receptor-mediated pathways
      are affected. This article discusses the fundamental role of the extracellular
      and intracellular molecules that initiate and control survival decisions by human
      Eos and highlights the role of the cis-trans isomerase, Pin1 in controlling these
      processes. 

PMID- 25563858
TI  - Clinical Evaluation of Laparoscopic-Assisted Percutaneous Endoscopic Gastrostomy
      (LAPEG).
AB  - Percutaneous endoscopic gastrostomy (PEG) is the standard modality for long-term
      enteral nutrition; however, complications are common. To avoid these
      complications, we introduce laparoscopic-assisted PEG (LAPEG) and describe its
      advantages. The aim of this study was to describe the advantages of LAPEG
      relative to other procedures. We retrospectively reviewed the records of 19
      patients who underwent LAPEG at our institution from June 2008 to February 2013.
      They were thought to be difficult cases for PEG. LAPEG was successfully performed
      in 18 patients (average age, 78.5 years; range, 50-98 years). The average
      surgical duration was 32.4 +/- 6.2 minutes. No major intraoperative or
      postoperative complications were observed. Feeding tubes were successfully placed
      in all patients within some days. LAPEG is a safe, effective, and simple
      procedure. The strongest advantage of LAPEG is the possibility of observing the
      intraperitoneal condition and the ability to perform PEG safely without any
      complications. LAPEG should be the first-choice procedure if it is difficult to
      accomplish conventional PEG. 

PMID- 25563860
TI  - Control of posture during tasks representing common work-related postures - a
      reliability study.
AB  - Assessment of control of posture using a task battery that represents work
      related postural conditions is highly recommended for providing a comprehensive
      understanding of collective postural demands. However, dearth of evidence exists
      on the reliability of a task battery, thus precluding its use as an outcome
      measure in field research. This study investigated the intrasession reliability
      and systematic variation of force plate derived centre of pressure (COP) measures
      obtained during repeated performance of a task battery (lifting task, limits of
      stability and bipedal and unipedal stance). COP signals obtained during each task
      performance were processed to derive various time-domain COP measures.
      Statistical analyses revealed that 13 of the 19 COP measures displayed excellent
      relative (ICC(2,3) >= 0.75) and acceptable absolute reliability (SEM%: <= 10).
      Although COP measures displayed systematic variation, the differences were less
      or equal to the measurement error, except COP measures of unipedal stance and
      limits of stability. The chosen task battery is reliable and can be used for
      comprehensive evaluation of control of posture, in both field and laboratory
      research. Practitioner Summary: Repeated evaluation of multiple tasks together
      sequentially could introduce measurement variability. This study investigated
      intrasession reliability of a task battery representing common work-related
      postures. The chosen task battery was found to be reliable with acceptable
      measurement error and can be used in field research settings for evaluation of
      control of posture. 

PMID- 25563861
TI  - Pacemakers and implantable cardioverter defibrillators, unknown to chest
      radiography: review, complications and systematic reading.
AB  - Chest X-ray is the imaging technique of choice for an initial study of pacemakers
      and implantable cardio-defibrillators (ICD). Radiologists have an important role
      in the evaluation of its initial placement and in the assessment during its
      follow-up. For this reason, it is necessary to know not only the different
      existing devices and its components but also the reasons of malfunction or
      possible complications. The purpose of this article is to do a systematic review
      of the different types of pacemakers and ICD. We review their usual radiological
      appearances, the possible complications which might take place and its causes of
      malfunctioning. 

PMID- 25563862
TI  - The Ebola threat: China's response to the West African epidemic and national
      development of prevention and control policies and infrastructure.
AB  - There is growing concern in West Africa about the spread of the Ebola hemorrhagic
      fever virus. With the increasing global public health risk, a coordinated
      international response is necessary. The Chinese government is prepared to work
      in collaboration with West African countries to assist in the containment and
      control of the epidemic through the contribution of medical expertise and mobile
      laboratory testing teams. Nationally, China is implementing prevention programs
      in major cities and provinces, the distribution of Ebola test kits, and the
      deployment of a new national Ebola research laboratory.

PMID- 25563863
TI  - Simultaneous direct detection of Shiga-toxin producing Escherichia coli (STEC)
      strains by optical biosensing with oligonucleotide-functionalized gold
      nanoparticles.
AB  - A simultaneous direct detection of Shiga-toxin producing strains of E. coli
      (STEC; "Big Six" - O26, O45, O103, O111, O121, and O145) as well as O157 strains
      by optical biosensing with oligonucleotide-functionalized gold nanoparticles
      (AuNPs) was developed. Initially, conserved regions of stx genes were amplified
      by asymmetric polymerase chain reaction (asPCR). Pairs of single stranded thiol
      modified oligonucleotides (30-mer) were immobilized onto AuNPs and used as probes
      to capture regions of stx1 (119-bp) and/or stx2 (104-bp) genes from STEC strains.
      DNA samples from pure cultures and food samples were sandwich hybridized with
      AuNP-oligo probes at optimal conditions (50  degrees C, 30 min). A complex was
      formed from the hybridization of AuNP-probes and target DNA fragments that
      retained the initial red color of the reaction solutions. For non-target DNA, a
      color change from red to purplish-blue was observed following an increase in salt
      concentration, thus providing the basis of simultaneous direct colorimetric
      detection of target DNA in the samples. Enrichment and pooling systems were
      incorporated to efficiently process a large number of food samples (ground beef
      and blueberries) and detection of live targets. The detection limit was <1 log
      CFU g(-1), requiring less than 1 h to complete after DNA sample preparation with
      100% specificity. Gel electrophoresis verified AuNP-DNA hybridization while
      spectrophotometric data and transmission electron microscope (TEM) images
      supported color discrimination based on the occurrence of molecular aggregation.
      In conclusion, the significant features of this approach took advantage of the
      unique colorimetric properties of AuNPs as a low-cost and simple approach yet
      with high specificity for simultaneous detection of STEC strains. 

PMID- 25563864
TI  - Early Drain Removal--The Middle Ground Between the Drain Versus No Drain Debate
      in Patients Undergoing Pancreaticoduodenectomy: A Prospective Validation Study.
AB  - OBJECTIVE: To perform an unbiased assessment of first postoperative day (POD 1)
      drain amylase level and pancreatic fistula (PF) after pancreaticoduodenectomy
      (PD). BACKGROUND: Recent evidence demonstrated that drain abandonment in PD is
      unsafe. Early drain amylase levels have been proposed as predictors of PF after
      PD, allowing for selection of patients for early drain removal. METHODS: Daily
      drain amylase levels were correlated with the development of PF in 2 independent
      cohorts of patients undergoing PD: training cohort (n = 126; year 2008) and
      validation cohort (n = 369; years 2009-2012). RESULTS: POD 1 drain amylase level
      had the highest predictive ability (concordance index: 0.911) for PF in the
      training cohort. An amylase level of 612 U/L or higher showed the best accuracy
      (86%), sensitivity (93%), and specificity (79%). Thus, a cutoff value of 600 U/L
      was utilized. In the validation cohort, 229 (62.1%) patients had a POD 1 drain
      amylase level of lower than 600 U/L, and PF developed in only 2 (0.9%) cases;
      whereas in patients with POD 1 drain amylase level of 600 U/L or higher (n = 140)
      the PF rate was 31.4% (odds ratio [OR] = 52, P < 0.0001). On multivariate
      analysis, POD 1 drain amylase level of lower than 600 U/L (OR = 0.0192, P <
      0.0001) was a stronger predictor of the absence of PF than pancreatic gland
      texture (OR = 0.193, P = 0.002) and duct diameter (OR = 0.861, P = 0.835).
      CONCLUSIONS: After PD, the risk of PF is less than 1% if POD 1 drain amylase
      level is lower than 600 U/L. We propose that in this group, which comprise more
      than 60% of patients, drains should be removed on POD 1.

PMID- 25563865
TI  - Tumor-associated Neutrophils and Malignant Progression in Intraductal Papillary
      Mucinous Neoplasms: An Opportunity for Identification of High-risk Disease.
AB  - OBJECTIVES: To evaluate the association of tumor-associated neutrophils (TANs)
      with malignant progression in intraductal papillary mucinous neoplasms (IPMNs)
      and to study the cyst fluid from these lesions for biomarkers of the inflammation
      carcinogenesis association. BACKGROUND: There is a strong link between TANs and
      malignant progression. Inflammatory mediators released by these cells may be a
      measurable surrogate marker of this progression. METHODS: We evaluated 78
      resected IPMNs (2004-2013). Lesions were divided into the low-risk (low- and
      intermediate-grade dysplasia: n = 48) and high-risk (high-grade dysplasia and
      invasive carcinoma: n = 30) groups. TANs were assessed and categorized (negative,
      low, and high). A multiplexed assay was performed to evaluate 87 different cyst
      fluid proteins, including cyst fluid inflammatory markers (CFIMs), as possible
      surrogate markers for parenchymal inflammation. RESULTS: Significant positive
      correlation between grade of dysplasia and TANs was found. High levels of TANs
      were identified in 2%, 33%, and 89% of the lesions when stratified by grade of
      dysplasia into low/intermediate-grade dysplasia, high-grade dysplasia, and
      invasive carcinoma, respectively (P < 0.001). Higher grades of dysplasia were
      also found to have positive correlation with 29 of the measured proteins, of
      which 23 (79%) were CFIMs. Higher levels of TANs correlated with higher levels of
      18 CFIMs, of which 16 (89%) were also found to be associated with higher grades
      of dysplasia. CONCLUSIONS: In this study, TANs were strongly associated with
      malignant progression in IPMNs. Measurement of CFIMs may be a surrogate marker
      for IPMN progression and allow for the identification of high-risk disease.

PMID- 25563866
TI  - Matched Case-Control Analysis Comparing Laparoscopic and Open Pylorus-preserving
      Pancreaticoduodenectomy in Patients With Periampullary Tumors.
AB  - OBJECTIVES: To evaluate the safety, feasibility, and oncologic outcomes of
      laparoscopic pylorus-preserving pancreaticoduodenectomy (L-PPPD) to treat
      periampullary tumors. The clinical outcomes of L-PPPD were compared with open
      pylorus-preserving pancreaticoduodenectomy (O-PPPD). BACKGROUND: Despite recent
      advances in laparoscopic pancreatic surgery, few studies have compared L-PPPD
      with O-PPPD. The safety, short-term clinical benefits, and oncologic outcomes of
      L-PPPD remain controversial. METHODS: Between January 2007 and December 2012, a
      total of 2192 patients diagnosed with periampullary tumors were treated with
      curative resection at our institution. Of these patients, 137 underwent a
      laparoscopic approach and 2055 an open technique. A retrospective study was
      performed to evaluate the safety, feasibility, and oncologic outcomes of L-PPPD
      compared with O-PPPD. RESULTS: The mean operation time for the L-PPPD group was
      longer than for the O-PPPD group (P < 0.001). Estimated blood loss was similar,
      as was the incidence of complications, such as pancreatic fistula and delayed
      gastric empting (P > 0.05). The mean number of analgesic injections administered
      was lower in the L-PPPD group than in the O-PPPD group (P < 0.001), and the mean
      duration of the postoperative hospital stays was shorter (P < 0.001). The
      surgical resection margins and the number of lymph nodes in the resected
      specimens did not differ between the 2 groups, and there was no significant
      difference in overall survival curves. CONCLUSIONS: L-PPPD had the typical
      advantages of minimally invasive abdominal procedures, such as less pain, shorter
      hospital stay, and quicker recovery. It is technically safe and feasible, and has
      favorable oncologic outcomes in comparison with O-PPPD in patients with
      periampullary tumors.

PMID- 25563868
TI  - Does Thoracic Epidural Analgesia Impede Recovery After Laparoscopic Colorectal
      Surgery?

PMID- 25563867
TI  - Prognostic Performance of Different Lymph Node Staging Systems After Curative
      Intent Resection for Gastric Adenocarcinoma.
AB  - OBJECTIVE: To compare the prognostic performance of American Joint Committee on
      Cancer/International Union Against Cancer seventh N stage relative to lymph node
      ratio (LNR), log odds of metastatic lymph nodes (LODDS), and N score in gastric
      adenocarcinoma. BACKGROUND: Metastatic disease to the regional LN basin is a
      strong predictor of worse long-term outcome following curative intent resection
      of gastric adenocarcinoma. METHODS: A total of 804 patients who underwent
      surgical resection of gastric adenocarcinoma were identified from a multi
      institutional database. The relative discriminative abilities of the different LN
      staging/scoring systems were assessed using the Akaike's Information Criterion
      (AIC) and the Harrell's concordance index (c statistic). RESULTS: Of the 804
      patients, 333 (41.4%) had no lymph node metastasis, whereas 471 (58.6%) had lymph
      node metastasis. Patients with >=N1 disease had an increased risk of death
      (hazards ratio = 2.09, 95% confidence interval: 1.68-2.61; P < 0.001]. When
      assessed using categorical cutoff values, LNR had a somewhat better prognostic
      performance (C index: 0.630; AIC: 4321.9) than the American Joint Committee on
      Cancer seventh edition (C index: 0.615; AIC: 4341.9), LODDS (C index: 0.615; AIC:
      4323.4), or N score (C index: 0.620; AIC: 4324.6). When LN status was modeled as
      a continuous variable, the LODDS staging system (C index: 0.636; AIC: 4304.0)
      outperformed other staging/scoring systems including the N score (C index: 0.632;
      AIC: 4308.4) and LNR (C index: 0.631; AIC: 4225.8). Among patients with LNR
      scores of 0 or 1, there was a residual heterogeneity of outcomes that was better
      stratified and characterized by the LODDS. CONCLUSIONS: When assessed as a
      categorical variable, LNR was the most powerful manner to stratify patients on
      the basis of LN status. LODDS was a better predicator of survival when LN status
      was modeled as a continuous variable, especially among those patients with either
      very low or high LNR.

PMID- 25563870
TI  - Living Donor Liver Transplantation in Children: Surgical and Immunological
      Results in 250 Recipients at Universite Catholique de Louvain.
AB  - OBJECTIVES: To evaluate the outcome of pediatric living donor liver
      transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO
      compatibility, and impact of maternal donation on graft acceptance. BACKGROUND:
      LDLT and ABO-mismatched transplantation constitute feasible options to alleviate
      organ shortage in children. Vascular complications of portal hypoplasia in
      biliary atresia (BA) and acute rejection (AR) are still major concerns in this
      field. METHODS: Data from 250 pediatric LDLT recipients, performed at Cliniques
      Universitaires Saint-Luc between July 1993 and June 2012, were collected
      retrospectively. Results were analyzed according to ABO matching and PV
      complications. Uni- and multivariate analyses were performed to study the impact
      of immunosuppression, sex matching, and maternal donation on AR rate. RESULTS:
      Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft
      loss nor vascular rejection, nor hemolysis, was encountered in the ABO
      nonidentical patients (n = 58), provided pretransplant levels of relevant
      isoagglutinins were below 1/16. In BA recipients, the rate of PV complications
      was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and
      to jump graft interposition (26.9%; P = 0.027). In parental donation, maternal
      grafts were associated with higher 1-year AR-free survival (55.2%) than paternal
      grafts (39.8%; P = 0.041), but only in BA patients. CONCLUSIONS: LDLT, including
      ABO-mismatched transplantation, constitutes a safe and efficient therapy for
      liver failure in children. In BA patients with PV hypoplasia, portoplasty seems
      to constitute the best technique for PV reconstruction. Maternal donation might
      be a protective factor for AR.

PMID- 25563872
TI  - Mesenteric Infarction: Clinical Outcomes After Restoration of Bowel Continuity.
AB  - INTRODUCTION: Patients who have a bowel resection for mesenteric infarction may
      require parenteral nutrition (PN). This study primarily aimed to determine the
      aetiological factors for a mesenteric infarction and the effects of restoring
      bowel continuity on the long-term PN requirements. METHODS: A retrospective
      review of data on patients treated for mesenteric infarction from 2000 to 2010.
      RESULTS: A total of 113 patients (61 women, median age 54 years) were identified.
      Seventy-four (65%) had a superior mesenteric artery thromboembolism, 25 (22%) had
      a superior mesenteric vein thrombosis, and 4 (3%) had superior mesenteric artery
      stricture or spasm. Patients younger than 60 years most commonly had a clotting
      abnormality (n = 23/46, 50%), whereas older patients had a cardiological risk
      factor (n = 11/17, 65%). All patients with a jejunostomy required long-term PN.
      Fifty-seven (49%) patients had restoration of bowel continuity (colon brought
      into circuit). After this, PN was stopped within 1 year in 20 (35%), within 2
      years in 29 (50%) patients and within 5 years in 44 (77%) patients (P = 0.001).
      CONCLUSIONS: A thrombotic tendency is the main etiological factor in most
      patients younger than 60 years. An anastomosis of the remaining jejunum to the
      colon can allow PN to be stopped.

PMID- 25563871
TI  - Relative Contributions of Complications and Failure to Rescue on Mortality in
      Older Patients Undergoing Pancreatectomy.
AB  - BACKGROUND: For pancreatectomy patients, mortality increases with increasing age.
      Our study evaluated the relative contribution of overall postoperative
      complications and failure to rescue rates on the observed increased mortality in
      older patients undergoing pancreatic resection at specialized centers. METHODS:
      We identified 2694 patients who underwent pancreatic resection from the American
      College of Surgeons' National Surgical Quality Improvement Pancreatectomy
      Demonstration Project at 37 high-volume centers. Overall morbidity and in
      hospital mortality were determined in patients younger than 80 years (N = 2496)
      and 80 years or older (N = 198). Failure to rescue was the number of deaths in
      patients with complications divided by the total number of patients with
      postoperative complications. RESULTS: No significant differences were observed
      between patients younger than 80 years and those 80 years or older in the rates
      of overall complications (41.4% vs 39.4%, P = 0.58). In-hospital mortality
      increased in patients 80 years or older compared to patients younger than 80
      years (3.0% vs 1.1%, P = 0.02). Failures to rescue rates were higher in patients
      80 years or older (7.7% vs 2.7%, P = 0.01). Across 37 high-volume centers,
      unadjusted complication rates ranged from 25.0% to 72.2% and failure to rescue
      rates ranged from 0.0% to 25.0%. Among patients with postoperative complications,
      comorbidities associated with failure to rescue were ascites, chronic obstructive
      pulmonary disease, and diabetes. Complications associated with failure to rescue
      included acute renal failure, septic shock, and postoperative pulmonary
      complications. CONCLUSIONS: In experienced hands, the rates of complications
      after pancreatectomy in patients 80 years or older compared to patients younger
      than 80 years were similar. However, when complications occurred, older patients
      were more likely to die. Interventions to identify and aggressively treat
      complications are necessary to decrease mortality in vulnerable older patients.

PMID- 25563873
TI  - Antibiotics and Right Iliac Fossa Pain: What Are We Actually Treating?

PMID- 25563874
TI  - Robotically assisted transanal total mesorectal excision: an exciting new trend
      in rectal cancer surgery.

PMID- 25563875
TI  - Transanal Total Mesorectal Excision: Will It Be A Valid Alternative in Rectal
      Cancer Surgery?

PMID- 25563876
TI  - Pediatric Emergency Appendectomy and 30-Day Postoperative Outcomes in District
      General Hospitals and Specialist Pediatric Surgical Centers in England, April
      2001 to March 2012: Retrospective Cohort Study.
AB  - OBJECTIVE: To compare trends in pediatric emergency appendectomy and adverse
      surgical outcomes between district general hospitals (DGHs) and specialist
      pediatric centers (SPCs). BACKGROUND: In the past decades in England, a
      significant reduction in the number of children operated by adult general
      surgeons has raised concerns about their surgical outcomes compared with
      specialist pediatric surgeons. METHODS: Using Hospital Episode Statistics, we
      analyzed patient-level data between April 2001 and March 2012. Main inclusion
      criteria were children younger than 16 years admitted to NHS-England hospitals
      for an emergency appendectomy. Main outcomes were annual age-sex adjusted
      appendectomy rates and postoperative risk of readmission, complication, and
      reintervention. RESULTS: A total of 83,679 emergency pediatric appendectomies
      were performed in 21 SPCs and 183 DGHs in England. SPCs performed only 18% of
      these operations (15,002). Annual age-sex standardized appendectomy rates fell
      from 87 to 68 per 100,000 population at an estimated 2% (rate ratio, 0.98) fall
      per annum. This was accompanied by a national annual increased risk of negative
      appendectomy, complication, reintervention, and readmission (adjusted odds ratio:
      1.02, 1.03, 1.04, and 1.06, respectively). Children who had appendectomies in
      DGHs had 28% more negative appendectomies, 11% more complications, and 11% more
      readmissions than those in SPCs. Postoperative length of stay was double in SPCs
      compared with DGHs (median, 4 vs 2 days). CONCLUSIONS: Major reductions in the
      number of pediatric emergency appendectomies in England over the past decade were
      associated with an overall increase in adverse surgical outcomes. Children
      operated in DGHs have more reinterventions, complications, and negative
      appendectomy rates than those operated in SPCs.

PMID- 25563877
TI  - Gut Lymphocyte Phenotype Changes After Parenteral Nutrition and Neuropeptide
      Administration.
AB  - OBJECTIVE: To define gut-associated lymphoid tissue (GALT) phenotype changes with
      parenteral nutrition (PN) and PN with bombesin (BBS). BACKGROUND: PN reduces
      respiratory tract (RT) and GALT Peyer patch and lamina propria lymphocytes,
      lowers gut and RT immunoglobulin A (IgA) levels, and destroys established RT
      antiviral and antibacterial immunity. BBS, an enteric nervous system
      neuropeptide, reverses PN-induced IgA and RT immune defects. METHODS: Experiment
      1: Intravenously cannulated ICR mice received chow, PN, or PN + BBS injections
      for 5 days. LSR-II flow cytometer analyzed Peyer patches and lamina propria
      isolated lymphocytes for homing phenotypes (L-selectin and LPAM-1) and state of
      activation (CD25, CD44) in T (CD3)-cell subsets (CD4 and CD8) along with homing
      phenotype (L-selectin and LPAM-1) in naive B (IgD) and antigen-activated (IgD or
      IgM) B (CD45R/B220) cells. Experiment 2: Following the initial experiment 1
      protocol, lamina propria T regulatory cell phenotype was evaluated by Foxp3
      expression. RESULTS: Experiment 1: PN significantly reduced lamina propria (1)
      CD4CD25 (activated) and (2) CD4CD25LPAM-1 (activated cells homed to the lamina
      propria) T cells, whereas PN-BBS assimilated chow levels. PN significantly
      reduced lamina propria (1) IgD (naive), (2) IgDLPAM (antigen-activated homed to
      the lamina propria) and CD44 memory B cells, whereas PN-BBS assimilated chow
      levels. Experiment 2: PN significantly reduced lamina propria CD4CD25Foxp3 T
      regulatory cells compared with chow-fed mice, whereas PN + BBS assimilated chow
      levels. CONCLUSIONS: PN reduces lamina propria activated and T regulatory cells
      and also naive and memory B cells. BBS addition to PN maintains these cell
      phenotypes, demonstrating the intimate involvement of the enteric nervous system
      in mucosal immunity.

PMID- 25563878
TI  - Constructing High-stakes Surgical Decisions: It's Better to Die Trying.
AB  - OBJECTIVE: To explore high-stakes surgical decision making from the perspective
      of seniors and surgeons. BACKGROUND: A majority of older chronically ill patients
      would decline a low-risk procedure if the outcome was severe functional
      impairment. However, 25% of Medicare beneficiaries have surgery in their last 3
      months of life, which may be inconsistent with their preferences. How patients
      make decisions to have surgery may contribute to this problem of unwanted care.
      METHODS: We convened 4 focus groups at senior centers and 2 groups of surgeons in
      Madison and Milwaukee, Wisconsin, where we showed a video about a decision
      regarding a choice between surgery and palliative care. We used qualitative
      content analysis to identify themes about communication and explanatory models
      for end-of-life treatment decisions. RESULTS: Seniors (n = 37) and surgeons (n =
      17) agreed that maximizing quality of life should guide treatment decisions for
      older patients. However, when faced with an acute choice between surgery and
      palliative care, seniors viewed this either as a choice between life and death or
      a decision about how to die. Although surgeons agreed that very frail patients
      should not have surgery, they held conflicting views about presenting treatment
      options. CONCLUSIONS: Seniors and surgeons highly value quality of life, but this
      notion is difficult to incorporate in acute surgical decisions. Some seniors use
      these values to consider a choice between surgery and palliative care, whereas
      others view this as a simple choice between life and death. Surgeons acknowledge
      challenges framing decisions and describe a clinical momentum that promotes
      surgical intervention.

PMID- 25563879
TI  - Efficacy of a Single Preoperative Dexamethasone Dose to Prevent Nausea and
      Vomiting After Thyroidectomy (the tPONV Study): A Randomized, Double-blind,
      Placebo-controlled Clinical Trial.
AB  - OBJECTIVE: Does dexamethasone given before thyroidectomy reduce postoperative
      nausea and vomiting (PONV) in a randomized controlled trial? BACKGROUND: PONV is
      an unsettling problem that commonly occurs in patients after thyroidectomy.
      Various preventive measures have been studied; however, many of these studies
      have been criticized for their biases (eg, use of opioids, sex selection) or were
      even retracted. METHODS: This single-institution, randomized, double-blind,
      placebo-controlled, superiority study was performed between January 1, 2011, and
      May 30, 2013. Patients undergoing thyroidectomy for benign disease were allocated
      by a block randomized list to receive a preoperative single dose of dexamethasone
      (8 mg) or placebo. Patients and staff were blinded to the treatment assignment.
      The primary endpoint was the incidence of PONV assessed at 4, 8, 16, 24, 32, and
      48 hours after surgery. To observe an incidence reduction of 50%, a total of 152
      patients were required for the study. RESULTS: The total incidence of PONV was
      reported in 65 of 152 patients (43%; 95% confidence interval [CI], 35-51). In the
      intention-to-treat analysis, PONV occurred in 22 of 76 patients (29%; 95% CI, 20
      40) in the treatment arm and in 43 of 76 patients (57%; 95% CI, 45-67) in the
      control arm (P = 0.001; odds ratio = 0.31; 95% CI, 0.16-0.61; absolute risk
      reduction = 28%; 95% CI, 12-42). The number needed to treat was 4. No severe
      dexamethasone-related adverse events were observed during the study. CONCLUSIONS:
      A single dose of preoperative dexamethasone administration is an effective, safe,
      and economical measure to reduce PONV incidence after thyroidectomy.

PMID- 25563881
TI  - Are we thinking? A commentary on "is partial-ALPPS safer than ALPPS? A single
      center experience".

PMID- 25563880
TI  - Unique Tracheal Fluid MicroRNA Signature Predicts Response to FETO in Patients
      With Congenital Diaphragmatic Hernia.
AB  - OBJECTIVE AND BACKGROUND: Our objective was to determine the fetal in vivo
      microRNA signature in hypoplastic lungs of human fetuses with severe isolated
      congenital diaphragmatic hernia (CDH) and changes in tracheal and amniotic fluid
      of fetuses undergoing fetoscopic endoluminal tracheal occlusion (FETO) to reverse
      severe lung hypoplasia due to CDH. METHODS: We profiled microRNA expression in
      prenatal human lungs by microarray analysis. We then validated this signature
      with real-time quantitative polymerase chain reaction in tracheal and amniotic
      fluid of CDH patients undergoing FETO. We further explored the role of miR-200b
      using semiquantitative in situ hybridization and immunohistochemistry for TGF
      beta2 in postnatal lung sections. We investigated miR-200b effects on TGF-beta
      signaling using a SMAD-luciferase reporter assay and Western blotting for phospho
      SMAD2/3 and ZEB-2 in cultures of human bronchial epithelial cells. RESULTS: CDH
      lungs display an increased expression of 2 microRNAs: miR-200b and miR-10a as
      compared to control lungs. Fetuses undergoing FETO display increased miR-200
      expression in their tracheal fluid at the time of balloon removal. Future
      survivors of FETO display significantly higher miR-200 expression than those with
      a limited response. miR-200b was expressed in bronchial epithelial cells and
      vascular endothelial cells. TGF-beta2 expression was lower in CDH lungs. miR-200b
      inhibited TGF-beta-induced SMAD signaling in cultures of human bronchial
      epithelial cells. CONCLUSIONS: Human fetal hypoplastic CDH lungs have a specific
      miR-200/miR-10a signature. Survival after FETO is associated with increased miR
      200 family expression. miR-200b overexpression in CDH lungs results in decreased
      TGF-beta/SMAD signaling.

PMID- 25563882
TI  - Clinical Health Service Research on the Surgical Therapy of Acute Appendicitis:
      Comparison of Outcomes Based on 3 German Multicenter Quality Assurance Studies
      Over 21 Years.
AB  - OBJECTIVE: The treatment of acute appendicitis has seen changes in diagnosis and
      therapy in Germany. The objective of this analysis was to assess changes in
      therapy and outcome after open appendectomy (OA) and laparoscopic appendectomy
      (LA) over the last 21 years. BACKGROUND: The analysis was based on 3 prospective
      multicenter quality assurance studies conducted by the Institute for Quality
      Control in Operative Medicine of the University of Magdeburg. METHODS: All
      inpatients with a diagnosis of appendicitis in these studies (1988/1989,
      1996/1997, 2008/2009) were included. Multiple linear and logistic regression
      analyses were performed. Statistical significance was set at P < 0.05. RESULTS:
      Data from 17,732 treatments of patients diagnosed with appendicitis were
      collected. The average age of patients increased between the 3 studies from 25.7
      to 34.6 years (P < 0.001). The preoperative selection of LA or OA was based on
      American Society of Anesthesiologists' classification (P < 0.001). Between
      1996/1997 and 2008/2009, the share of LA climbed from 33.1% to 85.8% (P < 0.001).
      In the study from 2008 to 2009, LA showed a significant advantage over the
      conventional technique in wound healing disturbances (P < 0.001) and the clinical
      duration of stay (P < 0.001). At no stage of appendix inflammation did LA
      significantly increase intra-abdominal abscesses. The use of a stapler is
      currently the most common method of appendiceal stump closure (83.6%).
      CONCLUSIONS: Changes in patient data reflected demographic changes. Preoperative
      selection leads to 2 clearly defined groups. LA is the most dominant method of
      current operative therapy. The negative selection in OA group has influenced the
      worse outcome of that group.

PMID- 25563884
TI  - Surgical Indications and Procedures for Resection of Hepatic Malignancies
      Confined to Segment VII.
AB  - OBJECTIVE: To establish a strategy for surgical resection of hepatic malignancies
      confined to segment VII. BACKGROUND: Various surgical procedures can be used to
      resect hepatic malignancies in segment VII, the deepest region of the liver, by
      open and/or laparoscopic approaches: nonanatomic wedge resection (WR),
      segmentectomy VII, right lateral sectionectomy (RLS), and right hepatectomy.
      METHODS: WR and segmentectomy VII were applied as first-line surgical procedures
      for colorectal liver metastasis (CRLM) and hepatocellular carcinoma (HCC),
      respectively. RLS and right hepatectomy were indicated only when tumor
      infiltration to the proximal Glissonian sheath was suspected. Operative outcomes
      were evaluated in 200 consecutive patients who underwent hepatic resection for
      HCC (n = 120) or CRLM (n = 80). RESULTS: WR, segmentectomy VII, RLS, and right
      hepatectomy were performed in 104 (52.0%), 57 (28.5%), 22 (11.0%), and 17 (8.5%)
      patients, respectively. Local hepatectomy (WR and segmentectomy VII) led to
      shorter operation times and lower blood loss volumes than did extensive
      hepatectomy (RLS and right hepatectomy). Thoracotomy was performed in half of the
      WR and two-thirds of the segmentectomy VII procedures. The availability of a
      laparoscopic approach was 40% (8 patients) after its application in October 2012.
      CONCLUSIONS: Even for hepatic malignancies located in segment VII, WR and
      segmentectomy should be prioritized over extensive hepatectomy to preserve the
      postoperative functional hepatic volume. Full mobilization of the right liver and
      a good surgical field provided by a large thoracoabdominal or abdominal incision
      or a laparoscopic approach are key factors for safe performance of deep hepatic
      transection.

PMID- 25563883
TI  - Differences in Physician Referral Drive Disparities in Surgical Intervention for
      Hepatocellular Carcinoma: A Retrospective Cohort Study.
AB  - OBJECTIVE: To determine whether sociodemographic and geographic factors are
      associated with referral for surgery and receipt of recommended surgical
      intervention. BACKGROUND: Surgical interventions confer survival advantages
      compared with palliative therapies for hepatocellular carcinoma (HCC), but
      disparities exist in use of surgical intervention. Few have investigated referral
      for surgery as a potential barrier to surgical intervention, and little is known
      about the effects of patient geographic factors, including proximity to surgical
      centers. METHODS: Data were abstracted from the Pennsylvania Cancer Registry for
      patients with a diagnosis of HCC from 2006 to 2011. Using hospital procedure
      volume data from the Pennsylvania Health Care Cost Containment Council, we
      calculated proximity to a surgical center. We used multivariable logistic
      regression to determine whether geographic, racial, socioeconomic, and clinical
      factors were associated with referral for surgery and receipt of a recommended
      surgical intervention. RESULTS: Of 3576 patients with HCC, 41.0% were referred
      for surgery. Patients who lived closer to a surgical center were less likely to
      be referred for surgery (adjusted odds ratio = 0.79; 95% confidence interval,
      0.68-0.92). Surgical referral was less likely among older, male patients with
      Medicaid insurance and advanced tumor stage at diagnosis. Of those referred, 1276
      (87.0%) underwent surgical intervention. Proximity to a surgical center was not
      associated with receipt of surgical intervention (P = 0.27). Patients with
      distant tumor stage at diagnosis were less likely to receive recommended surgical
      intervention (adjusted odds ratio = 0.27; 95% confidence interval, 0.15-0.50).
      CONCLUSIONS: Geographic and sociodemographic disparities in referral for surgery
      may be major barriers to surgical intervention for patients with HCC.

PMID- 25563887
TI  - Clinical Presentation of Patients With Tension Pneumothorax: A Systematic Review.
AB  - OBJECTIVE: To determine whether the reported clinical presentation of tension
      pneumothorax differs between patients who are breathing unassisted versus
      receiving assisted ventilation. BACKGROUND: Animal studies suggest that the
      pathophysiology and physical signs of tension pneumothorax differ by subject
      ventilatory status. METHODS: We searched electronic databases through to October
      15, 2013 for observational studies and case reports/series reporting clinical
      manifestations of tension pneumothorax. Two physicians independently extracted
      clinical manifestations reported at diagnosis. RESULTS: We identified 5 cohort
      studies (n = 310 patients) and 156 case series/reports of 183 cases of tension
      pneumothorax (n = 86 breathing unassisted, n = 97 receiving assisted
      ventilation). Hypoxia was reported among 43 (50.0%) cases of tension pneumothorax
      who were breathing unassisted versus 89 (91.8%) receiving assisted ventilation (P
      < 0.001). Pulmonary dysfunction progressed to respiratory arrest in 9.3% of cases
      breathing unassisted. As compared to cases who were breathing unassisted, the
      adjusted odds of hypotension and cardiac arrest were 12.6 (95% confidence
      interval, 5.8-27.5) and 17.7 (95% confidence interval, 4.0-78.4) times higher
      among cases receiving assisted ventilation. One cohort study reported that none
      of the patients with tension pneumothorax who were breathing unassisted versus
      39.6% of those receiving assisted ventilation presented without an arterial
      pulse. In contrast to cases breathing unassisted, the majority (70.4%) of those
      receiving assisted ventilation who experienced hypotension or cardiac arrest
      developed these signs within minutes of clinical presentation. DISCUSSION: The
      reported clinical presentation of tension pneumothorax depends on the ventilatory
      status of the patient. This may have implications for improving the diagnosis and
      treatment of this life-threatening disorder.

PMID- 25563888
TI  - Thickness-dependent structural arrangement in nano-confined imidazolium-based
      ionic liquid films.
AB  - A fundamental understanding of interfacial processes in nano-confined ionic
      liquids is crucial to increase the performance of modern energy storage devices.
      It is well-known that interfaces between electrodes and ionic liquids exhibit
      structures distinct from that of the bulk liquid. Following the recent interest
      in these systems, we studied the structure of thin ionic liquid films confined in
      flexible uncharged carbon nano-pores by using fully-atomistic molecular dynamics
      simulations. We show that the interfacial ions self-assemble into a closely
      packed chequerboard-like pattern, formed by both cations and anions in direct
      contact with the pore wall, and that within this structure we find changes
      dependent on the thickness of the confined films. At low coverages a dense layer
      is formed in which both the imidazolium-ring and its alkyl-tail lie parallel to
      the pore wall. With increasing coverage the alkyl-chains reorient perpendicular
      to the surface, making space for additional ions until a densified highly ordered
      layer is formed. This wall-induced self-patterning into interfacial layers with
      significantly higher than bulk density is consistent with recent experimental and
      theoretical studies of similar systems. This work reveals additional molecular
      level details on the effect of the film-thickness on the structure and density of
      the ionic liquid. 

PMID- 25563886
TI  - Glucose Transporter 1 (SLC2A1) and Vascular Endothelial Growth Factor A (VEGFA)
      Predict Survival After Resection of Colorectal Cancer Liver Metastasis.
AB  - OBJECTIVE: To investigate the individual and combined prognostic value of
      HIF1alpha, SLC2A1, and vascular endothelial growth factor A (VEGFA) in a multi
      institutional cohort of patients with resected colorectal cancer liver metastasis
      (CRCLM). BACKGROUND: In the majority of patients with CRCLM, resection seems not
      to be curative, despite its curative intent. Overexpression of hypoxia-inducible
      factor 1alpha (HIF1alpha), glucose transporter 1 (SLC2A1; also known as GLUT1),
      and VEGFA has been associated with tumor progression and poor prognosis of
      patients with colorectal cancer (CRC). METHODS: Tissue microarrays were generated
      using CRCLM and patient-matched primary CRC from patients who underwent CRCLM
      resection between 1990 and 2010. Prognostic value of HIF1alpha, SLC2A1, and VEGFA
      was determined by immunohistochemistry. A 500-fold cross-validated hazard rate
      ratio (HRRav) for overall survival was calculated. RESULTS: HIF1alpha, SLC2A1,
      and VEGFA expression could be evaluated in 328, 350, and 335 patients,
      respectively. High SLC2A1 expression was associated with good prognosis (HRRav,
      0.67; P (HRR >1)  < 0.01) and high VEGFA expression to poor prognosis (HRRav,
      1.84; P (HRR < 1)  = 0.02), also after multivariate analysis including
      established clinicopathological prognostic variables (HRRav, 0.67; P (HRR > 1)  <
      0.01 and HRRav, 1.50; P (HRR < 1)  = 0.02, respectively). SLC2A1 showed
      prognostic value particularly in patients treated with systemic therapy (P <
      0.01), whereas the prognostic value of VEGFA expression was mainly observed in
      patients not treated with systemic therapy (P < 0.01). Prognosis was especially
      poor in patients with both low SLC2A1 and high VEGFA expression (P < 0.01).
      HIF1alpha expression was not associated with survival. CONCLUSIONS: SLC2A1 and
      VEGFA expression are prognostic molecular biomarkers for patients with CRCLM with
      added value to established clinicopathological variables.

PMID- 25563889
TI  - Antibacterial activities against rice bacterial leaf blight and tomato bacterial
      wilt of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives.
AB  - In this study, a series of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole
      derivatives were synthesized and evaluated for their antibacterial activities
      against rice bacterial leaf blight and tomato bacterial wilt caused by
      Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (R. solanacearum)
      via the turbidimeter test in vitro. Antibacterial bioassays indicated that most
      compounds demonstrated appreciable antibacterial bioactivities against Xoo and R.
      solanacearum. Among the title compounds, compound 4i demonstrated the best
      inhibitory effect against Xoo and R. solanacearum with half-maximal effective
      concentration (EC50) values of 14.69 and 15.14MUg/mL, respectively, which were
      even better than those of commercial agents Bismerthiazol and Thiodiazole Copper.
      In vivo antibacterial activities tests under greenhouse conditions revealed that
      the control efficiency of compound 4i against rice bacterial leaf blight and
      tobacco bacterial wilt were better than those of Bismerthiazol and Thiodiazole
      Copper. Meanwhile, field trials also indicated that compound 4i demonstrated
      appreciable control efficiency against rice bacterial leaf blight and tomato
      bacterial wilt. 

PMID- 25563890
TI  - Hydroxamic acid based histone deacetylase inhibitors with confirmed activity
      against the malaria parasite.
AB  - Recent studies have highlighted a key role in regulating gene transcription, in
      both eukaryotes and prokaryotes, by enzymes that control the acetylation and
      deacetylation of histones. In particular, inhibitors of histone deacetylases
      (HDAC-Is) have been shown effective in controlling the development of many
      parasites, such as the plasmodium of malaria. Here we report the results of a
      study aimed at evaluating antiparasitic effect of two classes of HDAC-Is bearing
      different zinc binding group (hydroxamic acid vs thiol). The study showed that
      only the hydroxamic acid based HDAC inhibitors were active, with Plasmodium
      falciparum being the most sensitive parasite, having from low double-digit to
      single-digit nanomolar range in vitro activities. Among three derivatives
      evaluated also in vivo, ST8086AA1 (8) effectively inhibited 88% of the
      development of Plasmodium falciparum. 

PMID- 25563891
TI  - Synthesis and anticancer evaluation of novel triazole linked N-(pyrimidin-2
      yl)benzo[d]thiazol-2-amine derivatives as inhibitors of cell survival proteins
      and inducers of apoptosis in MCF-7 breast cancer cells.
AB  - A series of novel triazole linked N-(pyrimidin-2yl)benzo[d]thiazol-2-amine 5a-k
      were synthesized and evaluated for anticancer activity against breast (MCF-7),
      lung (A549) and skin (A375) cancer cell lines and their cytotoxic effects were
      compared against normal breast epithelial cells. The effect of compounds on cell
      cycle of MCF-7 breast cancer cell line was investigated by FACS. Result indicated
      G2/M cell cycle arrest of MCF-7 cells. Further promising compounds 5b, 5g, 5h and
      5i were tested for their apoptosis inducing ability as well as inhibitory
      activity against key proteins NF-kB, Survivin, CYP1A1, and ERK1/2 which help in
      cancer cell survival and proliferation. The apoptotic aspect of these compounds
      is further evidenced by increase in the activity of caspase-9 in MCF-7 cells.
      Hence these small molecules have the potential to control both the cell
      proliferation as well as the invasion process in highly malignant breast cancers
      and can be selected for further biological studies. 

PMID- 25563892
TI  - Photosensitive GFP mutants containing an azobenzene unnatural amino acid.
AB  - The incorporation of unnatural amino acids represents a unique mechanism for the
      modulation of protein function. This approach has been utilized to generate
      photoswitchable GFP mutants, capable of demonstrating modulated fluorescence upon
      exposure to UV irradiation. Overall these photosensitive GFP mutants can be
      employed in various biosensing and diagnostic techniques to better understand
      protein function and processing. 

PMID- 25563893
TI  - Waste management of printed wiring boards: a life cycle assessment of the metals
      recycling chain from liberation through refining.
AB  - Due to economic and societal reasons, informal activities including open burning,
      backyard recycling, and landfill are still the prevailing methods used for
      electronic waste treatment in developing countries. Great efforts have been made,
      especially in China, to promote formal approaches for electronic waste management
      by enacting laws, developing green recycling technologies, initiating pilot
      programs, etc. The formal recycling process can, however, engender environmental
      impact and resource consumption, although information on the environmental loads
      and resource consumption is currently limited. To quantitatively assess the
      environmental impact of the processes in a formal printed wiring board (PWB)
      recycling chain, life cycle assessment (LCA) was applied to a formal recycling
      chain that includes the steps from waste liberation through materials refining.
      The metal leaching in the refining stage was identified as a critical process,
      posing most of the environmental impact in the recycling chain. Global warming
      potential was the most significant environmental impact category after
      normalization and weighting, followed by fossil abiotic depletion potential, and
      marine aquatic eco-toxicity potential. Scenario modeling results showed that
      variations in the power source and chemical reagents consumption had the greatest
      influence on the environmental performance. The environmental impact from
      transportation used for PWB collection was also evaluated. The results were
      further compared to conventional primary metals production processes,
      highlighting the environmental benefit of metal recycling from waste PWBs.
      Optimizing the collection mode, increasing the precious metals recovery
      efficiency in the beneficiation stage and decreasing the chemical reagents
      consumption in the refining stage by effective materials liberation and
      separation are proposed as potential improvement strategies to make the recycling
      chain more environmentally friendly. The LCA results provide environmental
      information for the improvement of future integrated technologies and electronic
      waste management.

PMID- 25563894
TI  - Targeting microRNAs in epithelial-to-mesenchymal transition-induced cancer stem
      cells: therapeutic approaches in cancer.
AB  - INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) is a pathological
      phenomenon of cancer that confers tumor cells with increased cell motility,
      invasive and metastatic abilities with the acquisition of 'cancer stem-like cell'
      (CSC) phenotype. EMT endows tumor cells with intrinsic/acquired resistant
      phenotype at achievable doses of anticancer drugs and leads to tumor recurrence
      and progression. Besides the complex network of signaling pathways, microRNAs
      (miRNAs) are being evolved as a new player in the induction and regulation of
      EMT. AREAS COVERED: In this review article, the author has searched the PubMed
      and Google Scholar electronic databases for original research and review articles
      to gather current information on the association of EMT-induced CSCs with
      therapeutic resistance, tumor growth and metastasis, which are believed to be
      regulated by certain miRNAs. EXPERT OPINION: This review outlines not only the
      perspective on selective targeting of EMT-induced CSCs through altered expression
      of novel miRNAs and/or the use of conventional drugs that affect the levels of
      critical miRNAs but also the strategies on overcoming the drug resistance by
      interfering with EMT and modulating its associated pathways in CSCs that can be
      considered as potential therapeutic approaches toward eradicating the tumor
      recurrence and metastasis.

PMID- 25563896
TI  - Expanding evidence-based practice to service planning in child welfare.

PMID- 25563895
TI  - A successfully treated case of hypopituitarism complicated with hyperosmolar
      hyperglycaemic state and rhabdomyolysis.
AB  - INTRODUCTION: This study aimed to report a rare case of hypopituitarism
      complicated with hyperosmolar hyperglycaemic state and rhabdomyolysis. CASE
      PRESENTATION: Hypopituitarism is a clinical syndrome in which there is a
      deficiency in hormone production by the pituitary gland. It often leads to
      hypoglycaemia, but in this case the patient was complicated with hyperosmolar
      hyperglycaemic state. The patient received prompt medical treatment, which
      effectively prevented the occurrence of possible acute kidney failure and other
      complications. CONCLUSION: This is a complicated and rare case. Our report
      provides some indications for the timely diagnosis and the standardised
      treatments for a patient who has hypopituitarism complicated with hyperosmolar
      hyperglycaemic state and rhabdomyolysis.

PMID- 25563898
TI  - Effect of confinement on the mode dynamics of dipole clusters.
AB  - Dynamical properties of colloidal clusters composed of paramagnetic beads are
      presented. The clusters were trapped either in a parabolic trough or in a hard
      wall confinement. In order to access the dynamics of the ensembles, the
      instantaneous normal mode (INM) approach is utilized, which uses cluster
      configurations as an input. The peaks in the mode spectra weaken when the system
      size is increased and when the coupling strength is lowered. The short-time
      diffusive properties of the clusters are deduced using the INM technique. It is
      found that angular diffusion is always larger than radial diffusion regardless of
      the shape of the external trap. Further, short-time diffusion seems to be almost
      independent of the coupling strength in the solid regime, but decreases with
      increasing packing fraction and size of the ensembles. In general, it is found
      that diffusion is larger for parabolically confined than for hard-wall trapped
      clusters. 

PMID- 25563899
TI  - An accumulated activity effective index for promoting physical activity: a design
      and development study in a mobile and pervasive health context.
AB  - BACKGROUND: Increased physical activity has become a principal personal health
      goal worldwide because sufficient physical activity can reduce the risk of many
      adverse conditions. Motivating individuals to increase their levels of physical
      activity can increase life expectancy and contribute to a healthy life. Sharing
      and comparison of physical activity information by using the Internet, with fewer
      privacy concerns, might also help encourage people to promote and maintain
      sufficient physical activity. To promote and manage physical activity, an
      accumulated activity effective index (AAEI) is proposed in this paper. OBJECTIVE:
      The purpose of the AAEI design is to maintain and promote physical activity. The
      public can easily accept a clear indicator that reveals the current status of
      physical activity. The AAEI is not only an assessment and tracking tool for
      personal physical activity, but is also useful for goal setting and for sharing
      content with the Internet community. METHODS: The AAEI is derived from input in
      the form of accumulated physical activity, and evaluates the status of physical
      activities and days spent exercising. The term AAEI(t1,t2) is an index of the
      accumulated physical activity in the time interval (t1,t2), where the base unit
      of time is the day. The AAEI is determined according to accumulated physical
      activity and is adjusted using the previous status of physical activity. The
      previous status of physical activity is estimated according to the number of days
      spent exercising and the accumulated physical activity that has been performed.
      An analysis of the AAEI performance was conducted using a simulation model and a
      real-world trial with 2 participants. RESULTS: The AAEI increased as the physical
      activity and days spent exercising accumulated. Conversely, the AAEI decreased
      with lack of physical activity and increased resting days. In simulation, the
      shape of the AAEI line indicated different types of exercise. The moving average
      AAEI represented long-term exercise. In the real-world trial, the AAEI confirmed
      that the simulation results were comparable to actual conditions. CONCLUSIONS:
      The AAEI proposed in this paper is a method that can be used to evaluate the
      status of a person's physical activity. The AAEI is a simple numeric indication
      that is estimated by analyzing accumulated physical activity and the average
      number of days spent exercising. The AAEI is suitable for tracking personal
      physical activity, reminding the user of achievement goals, and allows data
      sharing by using the Internet. The results have demonstrated that the AAEI is a
      useful tool for physical activity management.

PMID- 25563900
TI  - Inhaled corticosteroids withdrawal in severe patients with chronic obstructive
      pulmonary disease: a wisdom decision?

PMID- 25563901
TI  - Effects of beta-blockers and tricyclic antidepressants on the activity of human
      organic anion transporting polypeptide 1A2 (OATP1A2).
AB  - The organic anion transporting polypeptide 1A2 (OATP1A2), a membrane drug
      transporter expressed on important organs (such as the brain, kidney, and
      intestine) may be a key element in the disposition of drugs. Previous studies
      demonstrated that it could transport a broad spectrum of substrates, including
      endogenous molecules and clinically relevant drugs, such as several beta-blockers
      and 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors. The primary objective of
      this study was to investigate OATP1A2 transport activity using rosuvastatin as a
      probe substrate and evaluate competitive inhibition of its transport by beta
      blockers. Rosuvastatin transport was saturable, with a Km of 60.2 uM. With the
      exception of carvedilol (IC50 of 3.2 uM), all of the other beta-blockers that
      were evaluated had a small or insignificant effect on OATP1A2-mediated uptake of
      rosuvastatin. Carvedilol differs from the other beta-blockers by the tricyclic
      moiety in its chemical structure. As a secondary objective, the transport of a
      series of tricyclic compounds by OATP1A2 and their potential for rosuvastatin
      transport inhibition were evaluated. Tricyclic compounds were not OATP1A2
      substrates. On the other hand, tricyclic compounds with a short aliphatic amine
      chain inhibited OATP1A2-mediated rosuvastatin transport. Our data suggest that
      these drugs may modulate the transport of OATP1A2 substrates and may affect drug
      actions. 

PMID- 25563903
TI  - Four cation-selective transporters contribute to apical uptake and accumulation
      of metformin in Caco-2 cell monolayers.
AB  - Metformin is the frontline therapy for type II diabetes mellitus. The oral
      bioavailability of metformin is unexpectedly high, between 40 and 60%, given its
      hydrophilicity and positive charge at all physiologic pH values. Previous studies
      in Caco-2 cell monolayers, a cellular model of the human intestinal epithelium,
      showed that during absorptive transport metformin is taken up into the cells via
      transporters in the apical (AP) membrane; however, predominant transport to the
      basolateral (BL) side occurs via the paracellular route because intracellular
      metformin cannot egress across the BL membrane. Furthermore, these studies have
      suggested that the AP transporters can contribute to intestinal accumulation and
      absorption of metformin. Transporter-specific inhibitors as well as a novel
      approach involving a cocktail of transporter inhibitors with overlapping
      selectivity were used to identify the AP transporters that mediate metformin
      uptake in Caco-2 cell monolayers; furthermore, the relative contributions of
      these transporters in metformin AP uptake were also determined. The organic
      cation transporter 1, plasma membrane monoamine transporter (PMAT), serotonin
      reuptake transporter, and choline high-affinity transporter contributed to
      approximately 25%, 20%, 20%, and 15%, respectively, of the AP uptake of
      metformin. PMAT-knockdown Caco-2 cells were constructed to confirm the
      contribution of PMAT in metformin AP uptake because a PMAT-selective inhibitor is
      not available. The identification of four intestinal transporters that contribute
      to AP uptake and potentially intestinal absorption of metformin is a significant
      novel finding that can influence our understanding of metformin pharmacology and
      intestinal drug-drug interactions involving this highly prescribed drug. 

PMID- 25563904
TI  - Prospective associations between socio-economic status and dietary patterns in
      European children: the Identification and Prevention of Dietary- and Lifestyle
      induced Health Effects in Children and Infants (IDEFICS) Study.
AB  - Exploring changes in children's diet over time and the relationship between these
      changes and socio-economic status (SES) may help to understand the impact of
      social inequalities on dietary patterns. The aim of the present study was to
      describe dietary patterns by applying a cluster analysis to 9301 children
      participating in the baseline (2-9 years old) and follow-up (4-11 years old)
      surveys of the Identification and Prevention of Dietary- and Lifestyle-induced
      Health Effects in Children and Infants Study, and to describe the cluster
      memberships of these children over time and their association with SES. We
      applied the K-means clustering algorithm based on the similarities between the
      relative frequencies of consumption of forty-two food items. The following three
      consistent clusters were obtained at baseline and follow-up: processed (higher
      frequency of consumption of snacks and fast food); sweet (higher frequency of
      consumption of sweet foods and sweetened drinks); healthy (higher frequency of
      consumption of fruits, vegetables and wholemeal products). Children with higher
      educated mothers and fathers and the highest household income were more likely to
      be allocated to the healthy cluster at baseline and follow-up and less likely to
      be allocated to the sweet cluster. Migrants were more likely to be allocated to
      the processed cluster at baseline and follow-up. Applying the cluster analysis to
      derive dietary patterns at the two time points allowed us to identify groups of
      children from a lower socio-economic background presenting persistently
      unhealthier dietary profiles. This finding reflects the need for healthy eating
      interventions specifically targeting children from lower socio-economic
      backgrounds. 

PMID- 25563902
TI  - The apoptotic mechanism of action of the sphingosine kinase 1 selective inhibitor
      SKI-178 in human acute myeloid leukemia cell lines.
AB  - We previously developed SKI-178 (N'-[(1E)-1-(3,4-dimethoxyphenyl)ethylidene]-3-(4
      methoxxyphenyl)-1H-pyrazole-5-carbohydrazide) as a novel sphingosine kinase-1
      (SphK1) selective inhibitor and, herein, sought to determine the mechanism-of
      action of SKI-178-induced cell death. Using human acute myeloid leukemia (AML)
      cell lines as a model, we present evidence that SKI-178 induces prolonged mitosis
      followed by apoptotic cell death through the intrinsic apoptotic cascade. Further
      examination of the mechanism of action of SKI-178 implicated c-Jun NH2-terminal
      kinase (JNK) and cyclin-dependent protein kinase 1 (CDK1) as critical factors
      required for SKI-178-induced apoptosis. In cell cycle synchronized human AML cell
      lines, we demonstrate that entry into mitosis is required for apoptotic induction
      by SKI-178 and that CDK1, not JNK, is required for SKI-178-induced apoptosis. We
      further demonstrate that the sustained activation of CDK1 during prolonged
      mitosis, mediated by SKI-178, leads to the simultaneous phosphorylation of the
      prosurvival Bcl-2 family members, Bcl-2 and Bcl-xl, as well as the
      phosphorylation and subsequent degradation of Mcl-1. Moreover, multidrug
      resistance mediated by multidrug-resistant protein1 and/or prosurvival Bcl-2
      family member overexpression did not affect the sensitivity of AML cells to SKI
      178. Taken together, these findings highlight the therapeutic potential of SKI
      178 targeting SphK1 as a novel therapeutic agent for the treatment of AML,
      including multidrug-resistant/recurrent AML subtypes. 

PMID- 25563905
TI  - Age-dependent changes in pattern recognition receptor and cytokine mRNA
      expression in children with otitis media with effusion.
AB  - OBJECTIVE: To investigate age-dependent changes in expression of pattern
      recognition receptors (PRRs) and cytokines in pediatric OME. MATERIALS AND
      METHODS: Ninety five pediatric patients with OME were divided into 4 age groups:
      0-2, 2-4, 4-7, and over 7 years. The presence of bacteria, and the levels of
      expression of mRNAs encoding Toll-like receptor (TLRs), NOD like receptors (NLRs)
      and cytokines in middle ear fluid were assessed, as were their correlations with
      age, gender, presence of bacteria and accompanying disease. RESULTS: Bacteria
      were detected in 32.6% of patients. The levels of expression of PRR and cytokine
      mRNAs tended to be lower in children aged 2-4 and 4-7 years. The levels of
      expression of TLR-2, TLR-9, NOD-1, NOD-2, IL-1, IL-6, and TNF-alpha mRNAs in
      effusion fluid were significantly lower in these two groups than in children aged
      0-2 and over 7 years (p<0.05 each). The levels of expression of TLR-4, TLR-5, TLR
      9, and NOD-1 mRNAs were significantly lower in culture positive than in culture
      negative patients (p<0.05 each). However, the expression levels of PRR and
      cytokine mRNAs were unrelated to gender and accompanying disease (p>0.05 each).
      CONCLUSIONS: The levels of expression of PRR and cytokine mRNAs differed by age
      in children with OME.

PMID- 25563906
TI  - Are distinct etiologies of upper airway obstruction in mouth-breathing children
      associated with different cephalometric patterns?
AB  - OBJECTIVE: To test the null hypothesis that mouth-breathing (MB) children by
      distinct obstructive tissues present a similar cephalometric pattern. METHODS:
      The sample included 226 prepubescent children (113 MB and 113 nasal breathing
      (NB) controls). An ENT clinical examination, including flexible nasal endoscopy,
      orthodontic clinical and cephalometric examinations, was performed on the MB
      population. MB children were grouped into three categories, according to the
      obstructive tissues: 1) adenoid group (AG), 2) tonsillar group (TG), and 3)
      adenotonsillar group (ATG). The NB controls were matched by gender, age, sagittal
      dental relationship and skeletal maturation status. Lateral cephalometric
      radiography provided the cephalometric pattern comparisons between the MB and NB
      groups. RESULTS: MB cephalometric measurements were significantly different from
      those of NB children, exception in the SNB degrees  (P=0.056). All comparisons
      between the three groups of MB children with the NB children showed a significant
      difference. Finally, even among the three groups of MB children, a significant
      difference was observed in the measurements of the SNB degrees  (P<0.036), NSGn
      degrees  (P<0.028) and PFH/TAFH ratio (posterior facial height/total anterior
      facial height) (P<0.012). CONCLUSIONS: The cephalometric pattern of MB and NB
      children was not similar. Cephalometric measurements of the MB group differed
      according to the etiology of upper airway obstruction. Children with isolated
      hypertrophy of the palatine tonsils presented with a mandible that was positioned
      more forward and upward compared to children obstructed only by the enlarged
      adenoid.

PMID- 25563907
TI  - Early Life Factors and Adult Leisure Time Physical Inactivity Stability and
      Change.
AB  - PURPOSE: Physical inactivity has a high prevalence and associated disease burden.
      A better understanding of influences on sustaining and changing inactive
      lifestyles is needed. We aimed to establish whether leisure time inactivity was
      stable in midadulthood and whether early life factors were associated with
      inactivity patterns. METHODS: In the 1958 British birth cohort (n = 12,271),
      leisure time inactivity (frequency, less than once a week) assessed at 33 and 50
      yr was categorized as "never inactive," "persistently inactive," "deteriorating,"
      or "improving." Early life factors (birth to 16 yr) were categorized into three
      (physical, social, and behavioral) domains. Using multinomial logistic
      regression, we assessed associations with inactivity persistence and change of
      factors within each early life domain and the three domains combined with and
      without adjustment for adult factors. RESULTS: Inactivity prevalence was similar
      at 33 and 50 yr (approximately 31%), but 17% deteriorated and 18% improved with
      age. In models adjusted for all domains simultaneously, factors associated with
      inactivity persistence versus never inactive were prepubertal stature (8% lower
      risk/height SD), poor hand control/coordination (17% higher risk/increase on four
      point scale), cognition (16% lower/SD in ability) (physical); parental divorce
      (25% higher), class at birth (7% higher/reduction on four-point scale), minimal
      parental education (16% higher), household amenities (2% higher/increase in 19
      point score (high = poor)) (social); and inactivity (22% higher/reduction in
      activity on four-point scale), low sports aptitude (47% higher), smoking (30%
      higher) (behavioral). All except stature, parental education, sports aptitude,
      and smoking were associated also with inactivity deterioration. Poor hand
      control/coordination was the only factor associated with improved status (13%
      lower/increase on four-point scale) versus persistently inactive. CONCLUSIONS:
      Adult leisure time inactivity is moderately stable. Early life factors are
      associated with persistent and deteriorating inactivity over decades in
      midadulthood but rarely with improvement.

PMID- 25563909
TI  - Neptunomonas phycophila sp. nov. isolated from a culture of Symbiodinium sp., a
      dinoflagellate symbiont of the sea anemone Aiptasia tagetes.
AB  - A Gram-stain-negative, facultatively anaerobic, oxidase- and catalase-positive,
      rod-shaped bacterium, strain SYM1(T), was isolated from a culture of Symbiodinium
      sp., an algal symbiont of the sea anemone Aiptasia tagetes collected in Puerto
      Rico. Growth was observed at 4-40  degrees C (optimum 30  degrees C), at pH 5.0
      11.0 (optimum pH 8.0) and with 0.5-8 % (optimum 2 %) (w/v) NaCl. Phylogenetic
      analyses of 16S rRNA gene sequences showed that strain SYM1(T) was a member of
      the genus Neptunomonas with the type strain of Neptunomonas naphthovorans as the
      closest phylogenetic relative with a pairwise sequence similarity of 98.15 %.
      However, DNA-DNA relatedness between strain SYM1(T) and N. naphthovorans CIP
      106451(T) was 24 %. Moreover, strain SYM1(T) could be distinguished from its
      closest relative by several phenotypic characteristics such as NaCl, pH and
      temperature tolerance, nitrate reduction and utilization of carbon substrates.
      The major cellular fatty acids were C16 : 0, C18 : 1omega7c and summed feature 3
      (comprising C16 : 1omega7c and/or iso-C15 : 0 2-OH). The genomic DNA G+C content
      of strain SYM1(T) was 45 mol%. Ubiquinone-8 (Q-8) was the only respiratory
      quinone detected. Based on a polyphasic taxonomic characterization, strain
      SYM1(T) represents a novel species of the genus Neptunomonas, for which the name
      Neptunomonas phycophila sp. nov. is proposed. The type strain is SYM1(T) ( = LMG
      28329(T) = CECT 8716(T)). 

PMID- 25563908
TI  - Effects of Increased Loading on In Vivo Tendon Properties: A Systematic Review.
AB  - INTRODUCTION: In vivo measurements have been used in the past two decades to
      investigate the effects of increased loading on tendon properties, yet the
      current understanding of tendon macroscopic changes to training is rather
      fragmented, limited to reports of tendon stiffening, supported by changes in
      material properties and/or tendon hypertrophy. The main aim of this review was to
      analyze the existing literature to gain further insights into tendon adaptations
      by extracting patterns of dose-response and time-course. METHODS: PubMed/Medline,
      SPORTDiscus, and Google Scholar databases were searched for studies examining the
      effect of training on material, mechanical, and morphological properties via
      longitudinal or cross-sectional designs. RESULTS: Thirty-five of 6440 peer
      reviewed articles met the inclusion criteria. The key findings were i) the
      confirmation of a nearly systematic adaptation of tendon tissue to training, ii)
      the important variability in the observed changes in tendon properties between
      and within studies, and iii) the absence of a consistent incremental pattern
      regarding the dose-response or the time-course relation of tendon adaptation
      within the first months of training. However, long-term (years) training was
      associated with a larger tendon cross-sectional area, without any evidence of
      differences in material properties. Our analysis also highlighted several gaps in
      the existing literature, which may be addressed in future research. CONCLUSIONS:
      In line with some cross-species observations about tendon design, tendon cross
      sectional area allegedly constitutes the ultimate adjusting parameter to
      increased loading. We propose here a theoretical model placing tendon hypertrophy
      and adjustments in material properties as parts of the same adaptive continuum.

PMID- 25563910
TI  - Haloarchaeobius salinus sp. nov., isolated from an inland salt lake, and emended
      description of the genus Haloarchaeobius.
AB  - The halophilic archaeal strain, YC82(T), was isolated from Yuncheng salt lake in
      Shanxi, PR China. Cells from strain YC82(T) were Gram-stain negative, pleomorphic
      rods, which lysed in distilled water and formed light-red colonies on solid
      media. Strain YC82(T) grew at 25-50  degrees C (optimum 37  degrees C), in 1.4
      4.8 M NaCl (optimum 2.0 M), in 0-1.0 M MgCl2 (optimum 0.05 M) and at pH 6.0-9.5
      (optimum pH 7.5). The major polar lipids of strain YC82(T) were phosphatidic
      acid, phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester,
      phosphatidylglycerol sulfate and three glycolipids, which were
      chromatographically identical to those of Haloarchaeobius iranensis IBRC-M
      10013(T) and Haloarchaeobius litoreus CGMCC 1.10390(T). 16S rRNA gene analysis
      revealed that strain YC82(T) had two dissimilar 16S rRNA genes and that it was
      phylogenetically related to Hab. iranensis IBRC-M 10013(T) (94.3-99.0 %
      nucleotide identity) and Hab. litoreus CGMCC 1.10390(T) (94.1-98.8 % nucleotide
      identity). The rpoB' gene similarities between strain YC82(T) and Hab. iranensis
      IBRC-M 10013(T) and Hab. litoreus CGMCC 1.10390(T) were 96.5 % and 95.7 %,
      respectively. The DNA G+C content of strain YC82(T) was 63.7 mol%. Strain YC82(T)
      showed low DNA-DNA relatedness with Hab. iranensis IBRC-M 10013(T) and Hab.
      litoreus CGMCC 1.10390(T). The phenotypic, chemotaxonomic and phylogenetic
      properties of strain YC82(T) ( = CGMCC 1.12232(T) = JCM 18644(T)) suggest that it
      represents a novel species of the genus Haloarchaeobius, for which the name
      Haloarchaeobius salinus sp. nov. is proposed. An emended description of the genus
      Haloarchaeobius is also presented. 

PMID- 25563911
TI  - Mucilaginibacter gotjawali sp. nov., isolated from soil of a lava forest.
AB  - A novel bacterial strain, designated SA3-7(T), was isolated from soil of a lava
      forest located in Jeju, Republic of Korea. Cells of strain SA3-7(T) were Gram
      stain-negative, oxidase- and catalase-positive, non-motile rods and produced
      creamy white colonies on ten-fold-diluted R2A agar. The isolate contained
      menaquinone-7 (MK-7) as the predominant isoprenoid quinone and summed feature 3
      (C16 : 1omega7c/C16 : 1omega6c), iso-C15 : 0 and iso-C17 : 0 3-OH as the major
      fatty acids. The DNA G+C content was 43.1 mol%. Phylogenetic analysis based on
      16S rRNA gene sequencing showed that strain SA3-7(T) was related most closely to
      Mucilaginibacter frigoritolerans FT22(T) (96.7 % sequence similarity) and that it
      formed a separate lineage in the genus Mucilaginibacter. Combined phenotypic,
      chemotaxonomic and phylogenetic characteristics supported the conclusion that
      strain SA3-7(T) represents a novel species of the genus Mucilaginibacter, for
      which the name Mucilaginibacter gotjawali sp. nov. is proposed; the type strain
      is SA3-7(T) ( = KCTC 32515(T) = CECT 8628(T) = DSM 29289(T)). 

PMID- 25563912
TI  - Acinetobacter seifertii sp. nov., a member of the Acinetobacter calcoaceticus
      Acinetobacter baumannii complex isolated from human clinical specimens.
AB  - This study aimed to define the taxonomic status of a phenetically distinct group
      of 16 strains that corresponds to Acinetobacter genomic species 'close to 13TU',
      a provisional genomic species of the Acinetobacter calcoaceticus-Acinetobacter
      baumannii (ACB) complex recognized by Gerner-Smidt and Tjernberg in 1993. These
      strains have been isolated in different countries since the early 1990s and were
      mostly recovered from human clinical specimens. They were compared with 45
      reference strains representing the known taxa of the ACB complex using taxonomic
      methods relevant to the genus Acinetobacter. Based on sequence analysis of the
      concatenated partial sequences (2976 bp) of seven housekeeping genes, the 16
      strains formed a tight and well-supported cluster (intracluster sequence identity
      of >=98.4 %) that was clearly separated from the other members of the ACB complex
      (<=94.7 %). The species status of the group was supported by average nucleotide
      identity values of <=91.7 % between the whole genome sequence of representative
      strain NIPH 973(T) (NCBI accession no. APOO00000000) and those of the other
      species. In addition, whole-cell matrix-assisted laser desorption ionization-time
      of-flight (MALDI-TOF) MS analyses indicated the distinctness of the group at the
      protein level. Metabolic and physiological tests revealed several typical
      features of the group, although they did not allow its reliable differentiation
      from the other members of the ACB complex. We conclude that the 16 strains
      represent a distinct novel species, for which we propose the name Acinetobacter
      seifertii sp. nov. The type strain is NIPH 973(T) ( = CIP 110471(T) = CCUG
      34785(T) = CCM 8535(T)). 

PMID- 25563913
TI  - Clostridium oryzae sp. nov., from soil of a Japanese rice field.
AB  - An obligately anaerobic bacterial strain designated KC3(T) was isolated from a
      rice straw-degrading culture, for which soil of a Japanese rice field was used as
      the inoculum. Cells of strain KC3(T) were determined to be non-cellulolytic, Gram
      stain-positive, non-motile, ellipsoidal, spore-forming rods, 0.8-1*4-25 um.
      Endospores were formed at a terminal position in elongated cells (12-25 um, mean
      15 um). The temperature range for growth was 20-50  degrees C, with an optimum at
      37  degrees C. The pH range for growth was 5.0-7.5, with an optimum at pH 6.0
      (slightly acidophilic). Strain KC3(T) fermented cellobiose to lactate, butyrate,
      acetate, formate, hydrogen and carbon dioxide. The major cellular fatty acids
      (>10 %) were C14 : 0, C16 : 0 and C19 : 0 cyclo 11,12 dimethylacetal. The DNA G+C
      content of strain KC3(T) was 37.5 mol%. 16S rRNA gene sequence analysis revealed
      that strain KC3(T) shared low sequence similarity (<93 %) with type strains of
      the genus Clostridium sensu stricto (Clostridium rRNA cluster I). Analyses of the
      DNA gyrase A and ATP synthase beta subunit sequences supported the affiliation of
      strain KC3(T) to the genus Clostridium sensu stricto. The evidence presented here
      indicates that strain KC3(T) represents a novel species of the genus Clostridium,
      for which the name Clostridium oryzae sp. nov. is proposed. The type strain of
      Clostridium oryzae is KC3(T) ( = DSM 28571(T) = NBRC 110163(T)). 

PMID- 25563914
TI  - Hydrobacter penzbergensis gen. nov., sp. nov., isolated from purified water.
AB  - A Gram-negative, oxidase- and catalase-positive bacterium, designated strain EM
      4(T), which varied in shape from rod-shaped to curved or helical with frequently
      observed bulb-shaped protuberances, was isolated from purified water. 16S rRNA
      gene sequence analysis indicated that the novel strain belongs to the family
      Chitinophagaceae within the phylum Bacteroidetes; the closest relative among
      bacterial species with validly published names was determined to be
      Sediminibacterium salmoneum NBRC 103935(T), with 93.4 % sequence identity. The
      main fatty acids of strain EM 4(T) were iso-C15 : 0, iso-C15 : 1 and iso-C17 : 0
      3-OH. The polar lipid profile consisted of phosphatidylethanolamine, aminolipids,
      aminophospholipids and unknown lipids; the quinone system consisted of
      menaquinone MK-7. 16S rRNA gene sequence analysis and the polar lipid and fatty
      acid profiles suggest that the strain represents a novel genus and species, for
      which the name Hydrobacter penzbergensis gen. nov., sp. nov. is proposed. The
      type strain of Hydrobacter penzbergensis is strain EM 4(T) ( = DSM 25353(T) =
      CCUG 62278(T)). 

PMID- 25563916
TI  - Burkholderia megalochromosomata sp. nov., isolated from grassland soil.
AB  - A Gram-stain negative, rod-shaped, non-spore-forming, obligate aerobic bacterial
      strain, JC2949(T), was isolated from grassland soil in Gwanak Mountain, Seoul,
      Republic of Korea. Phylogenetic analysis, based on 16S rRNA sequences, indicated
      that strain JC2949(T) belongs to the genus Burkholderia, showing highest sequence
      similarities with Burkholderia grimmiae R27(T) (98.8 %), Burkholderia cordobensis
      LMG 27620(T) (98.6 %), Burkholderia jiangsuensis MP-1T(T) (98.6 %), Burkholderia
      zhejiangensis OP-1(T) (98.5 %), Burkholderia humi LMG 22934(T) (97.5 %),
      Burkholderia terrestris LMG 22937(T) (97.3 %), Burkholderia telluris LMG 22936(T)
      (97.2 %) and Burkholderia glathei ATCC 29195(T) (97.0 %). The major fatty acids
      of strain JC2949(T) were C18 : 1omega7c, summed feature 3 (C16 : 1omega7c and/or
      C16 : 1omega6c) and C16 : 0. Its predominant polar lipids were
      phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and an
      unknown amino phospholipid. The dominant isoprenoid quinone was ubiquinone Q-8.
      The pairwise average nucleotide identity values between strain JC2949(T) and the
      genomes of 30 other species of the genus Burkholderia ranged from 73.4-90.4 %,
      indicating that the isolate is a novel genomic species within this genus. Based
      on phenotypic and chemotaxonomic comparisons, it is clear that strain JC2949(T)
      represents a novel species of the genus Burkholderia. We propose the name for
      this novel species to be Burkholderia megalochromosomata sp. nov. The type strain
      is JC2949(T) ( = KACC 17925(T) = JCM 19905(T)). 

PMID- 25563915
TI  - Microbacterium panaciterrae sp. nov., isolated from the rhizosphere of ginseng.
AB  - Strain DCY56(T) was isolated from a soil sample taken from a ginseng field. The
      strain was Gram-reaction positive, catalase-positive, oxidase-negative, aerobic
      and non-motile. Phylogenetic analysis, based on 16S rRNA gene sequence analysis,
      indicated that strain DCY56(T) belonged to the genus Microbacterium. The closest
      relatives were Microbacterium azadirachtae AI-S262(T), Microbacterium aerolatum V
      73(T) and Microbacterium phyllosphaerae DSM 13468(T) (98.0 %, 98.0 % and 97.5 %
      gene sequence similarity, respectively). The G+C content of the genomic DNA of
      strain DCY56(T) was 68.5 mol%. The DNA-DNA relatedness values between strain
      DCY56(T) and the most closely related type strains were lower than 36 %. The
      major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and an
      unidentified glycolipid. The predominant fatty acids contained iso-C16 : 0,
      anteiso-C15 : 0 and anteiso-C17 : 0. The menaquinones were MK-12 and MK-13. The
      diagnostic diamino acid of strain DCY56(T) was ornithine. The dominant whole-cell
      sugars were glucose, rhamnose and ribose. The results of the genotypic analysis,
      in combination with chemotaxonomic and physiological data, demonstrate that
      strain DCY56(T) represents a novel species within the genus Microbacterium, for
      which the name Microbacterium panaciterrae sp. nov. is proposed. The type strain
      is DCY56(T) ( = KCTC 19884(T) = JCM 17839(T)). 

PMID- 25563917
TI  - Hafnia psychrotolerans sp. nov., isolated from lake water.
AB  - A psychrotolerant, Gram-stain-negative, motile, aerobic, peritrichous bacterium,
      strain DJC1-1(T), was isolated from Lake Dajiaco, Tibetan Plateau, China. The
      strain was negative for citrate utilization, lipase activity and alpha
      glucosidase, but positive for the Voges-Proskauer reaction and N-acetyl-beta
      glucosaminidase. 16S rRNA gene sequence analysis indicated that Hafnia paralvei
      ATCC 29927(T), Hafnia alvei ATCC 13337(T), Serratia grimesii DSM 30063(T) and
      Serratia plymuthica DSM 4540(T) were the closest relatives of strain DJC1-1(T),
      with similarities of 97.76, 96.80, 97.71 and 97.58 %, respectively. The DNA G+C
      content of strain DJC1-1(T) was 53.9 mol%. The predominant fatty acids were C16 :
      0 and C17 : 0 cyclo. Based on these characteristics, strain DJC1-1(T) can be
      assigned to the genus Hafnia. In DNA-DNA hybridization tests, strain DJC1-1(T)
      shared 50.6, 35.1, 36.5 and 18.1 % DNA-DNA relatedness with the type strains of
      H. paralvei, H. alvei, S. grimesii and S. plymuthica, respectively. The growth
      temperature ranged from 0 to 40  degrees C, with optimum growth at 15  degrees C.
      Physiological and biochemical tests differentiated strain DJC1-1(T) from the type
      strains of recognized species of the genus Hafnia. Therefore, strain DJC1-1(T) is
      identified as representing a novel species of the genus Hafnia, for which the
      name Hafnia psychrotolerans sp. nov. is proposed. The type strain is DJC1-1(T) (
      = JCM 30077(T) = CGMCC1.12806(T)). 

PMID- 25563919
TI  - Flavobacterium daemonensis sp. nov., isolated from Daemo Mountain soil.
AB  - A Gram-staining-negative, catalase- and oxidase-positive, obligately aerobic,
      motile by gliding, bright yellow and rod-shaped bacterial strain was isolated
      from soil of Daemo Mountain (Daemosan) in Seoul, Republic of Korea. Its taxonomic
      position was investigated by using a polyphasic study. On the basis of 16S rRNA
      gene sequence comparisons, strain THG-DJ7(T) was found to be most closely related
      to Flavobacterium denitrificans ED5(T) (97.9 % sequence similarity),
      Flavobacterium ginsenosidimutans THG 01(T) (97.6 %), Flavobacterium kyungheensis
      THG-107(T) (97.5 %), Flavobacterium anhuiense D3(T) (97.1 %) and Flavobacterium
      ginsengisoli DCY54(T) (97.0 %). The DNA-DNA relatedness between strain THG-DJ7(T)
      and its phylogenetically closest neighbours was below 40.0 %. The G+C content of
      the genomic DNA was determined to be 32.6 mol%. The only isoprenoid quinone
      detected in strain THG-DJ7(T) was menaquinone-6 (MK-6). The major component in
      the polyamine pattern was sym-homospermidine. The major polar lipids were found
      to be phosphatidylethanolamine, phosphatidyldimethylethanolamine, an unidentified
      aminophosphoglycolipid, phosphatidylserine and an unidentified lipid. The major
      fatty acids were identified as iso-C15 : 0, iso-C15 : 0 3-OH and summed feature 3
      (comprising C16 : 1omega7c and/or C16 : 1omega6c). These data support the
      affiliation of strain THG-DJ7(T) to the genus Flavobacterium. We report the
      phenotypic, genotypic and phylogenetic characterization of strain THG-DJ7(T).
      Based on the findings presented, a novel species of the genus Flavobacterium,
      Flavobacterium daemonensis sp. nov. is proposed, with THG-DJ7(T) ( = KACC
      17651(T) = JCM 19455(T)) as the type strain. 

PMID- 25563918
TI  - Rickettsia buchneri sp. nov., a rickettsial endosymbiont of the blacklegged tick
      Ixodes scapularis.
AB  - We obtained a rickettsial isolate from the ovaries of the blacklegged tick,
      Ixodes scapularis. The isolate (ISO7(T)) was grown in the Ixodes ricinus
      embryonic cell line IRE11. We characterized the isolate by transmission electron
      microscopy and gene sequencing. Phylogenetic analysis of 11 housekeeping genes
      demonstrated that the isolate fulfils the criteria to be classified as a
      representative of a novel rickettsial species closely related to 'Rickettsia
      monacensis'. These rickettsiae form a clade separate from other species of
      rickettsiae. Gene sequences indicated that several genes important in rickettsial
      motility, invasiveness and temperature adaptation were mutated (e.g. sca2, rickA,
      hsp22, pldA and htrA). We propose the name Rickettsia buchneri sp. nov. for this
      bacterium that infects the ovaries of the tick I. scapularis to acknowledge the
      pioneering contributions of Professor Paul Buchner (1886-1978) to research on
      bacterial symbionts. The type strain of R. buchneri sp. nov. is strain ISO-7(T) (
      = DSM 29016(T) = ATCC VR-1814(T)). 

PMID- 25563920
TI  - Mucinivorans hirudinis gen. nov., sp. nov., an anaerobic, mucin-degrading
      bacterium isolated from the digestive tract of the medicinal leech Hirudo
      verbana.
AB  - Three anaerobic bacterial strains were isolated from the digestive tract of the
      medicinal leech Hirudo verbana, using mucin as the primary carbon and energy
      source. These strains, designated M3(T), M4 and M6, were Gram-stain-negative, non
      spore-forming and non-motile. Cells were elongated bacilli approximately 2.4 um
      long and 0.6 um wide. Growth only occurred anaerobically under mesophilic and
      neutral pH conditions. All three strains could utilize multiple simple and
      complex sugars as carbon sources, with glucose fermented to acid by-products. The
      DNA G+C contents of strains M3(T), M4 and M6 were 44.9, 44.8 and 44.8 mol%,
      respectively. The major cellular fatty acid of strain M3(T) was iso-C15 : 0.
      Phylogenetic analysis of full-length 16S rRNA gene sequences revealed that the
      three strains shared >99 % similarity with each other and represent a new lineage
      within the family Rikenellaceae of the order Bacteroidales, phylum Bacteroidetes.
      The most closely related bacteria to strain M3(T) based on 16S rRNA gene
      sequences were Rikenella microfusus DSM 15922(T) (87.3 % similarity) and
      Alistipes finegoldii AHN 2437(T) (87.4 %). On the basis of phenotypic, genotypic
      and physiological evidence, strains M3(T), M4 and M6 are proposed as representing
      a novel species of a new genus within the family Rikenellaceae, for which the
      name Mucinivorans hirudinis gen. nov., sp. nov. is proposed. The type strain of
      Mucinivorans hirudinis is M3(T) ( = ATCC BAA-2553(T) = DSM 27344(T)). 

PMID- 25563921
TI  - Pedobacter ureilyticus sp. nov., isolated from tomato rhizosphere soil.
AB  - A Gram-stain-negative, strictly aerobic, rod-shaped and pinkish-yellow bacterium,
      which was motile by gliding and designated strain THG-T11(T), was isolated from
      tomato rhizosphere soil in Gyeonggi province, Republic of Korea. Based on 16S
      rRNA gene sequence comparisons, strain THG-T11(T) was found to be most closely
      related to 'Pedobacter zeaxanthinifaciens' TDMA-5 (95.9 % sequence similarity),
      Pedobacter agri PB92(T) (94.9 %), Pedobacter rhizosphaerae 01-96(T) (94.6 %) and
      Pedobacter alluvionis NWER-II11(T) (94.5 %). The DNA G+C content was 38.4 mol%.
      The only isoprenoid quinone detected in strain THG-T11(T) was menaquinone-7 (MK
      7). The major component in the polyamine pattern was sym-homospermidine. The
      major polar lipids were phosphatidylethanolamine, an unidentified
      phosphoglycolipid, an unidentified glycolipid, an unidentified lipid,
      unidentified aminophospholipids and unidentified aminolipids. The major ceramide
      was found to be ceramide phosphorylethanolamine. The major fatty acids were
      identified as iso-C15 : 0, summed feature 3 (C16 : 1omega7c and/or C16 :
      1omega6c) and C16 : 0. These data support the affiliation of strain THG-T11(T) to
      the genus Pedobacter. Based on phenotypic, chemotaxonomic and phylogenetic
      analysis, it is proposed that strain THG-T11(T) represents a novel species of the
      genus Pedobacter for which the name Pedobacter ureilyticus sp. nov. is proposed,
      with THG-T11(T) as the type strain ( = KACC 17660(T) = JCM 19461(T)). 

PMID- 25563922
TI  - Flavobacterium palustre sp. nov., isolated from wetland soil.
AB  - A Gram-staining-negative, non-motile, yellow-coloured, rod-shaped bacterium,
      designated S44(T), was isolated from bankside soil of Xixi wetland, located in
      Zhejiang province, China. Growth of strain S44(T) was observed at 6-37  degrees C
      (optimum, 28  degrees C) and at pH 6.0-9.0 (optimum, 7.0). No growth occurred in
      the presence of >2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that strain S44(T) represented a member of the genus
      Flavobacterium, showing the highest sequence similarities to the sequences from
      Flavobacterium succinicans DSM 4002(T) (96.9 %), Flavobacterium reichenbachii WB
      3.2-61(T) (96.6 %) and Flavobacterium glycines NCBI 105008(T) (96.5 %). The G+C
      content of the genomic DNA was 33.6 mol%. The predominant cellular fatty acids
      were C15 : 0, iso-C15 : 0, anteiso-C15 : 0 and summed feature 3 (comprising C16 :
      1omega7c and/or iso-C15 : 0 2-OH), and the major respiratory quinone was
      menaquinone 6 (MK-6). The major polar lipids were phosphatidylethanolamine, two
      unknown aminolipids, two unknown aminophospholipids and four unknown polar
      lipids. On the basis of the phenotypic and genotypic data, it is proposed that
      the isolate S44(T) be classified as representing a novel species of the genus
      Flavobacterium, for which the name Flavobacterium palustre sp. nov. is proposed.
      The type strain is S44(T) ( = CGMCC 1.12811(T) = NBRC 110389(T)). 

PMID- 25563923
TI  - Garicola koreensis gen. nov., sp. nov., isolated from saeu-jeot, traditional
      Korean fermented shrimp.
AB  - A novel Gram-staining-positive, non-endospore-forming, aerobic bacterium,
      designated strain SJ5-4(T), was isolated from seau-jeot, a traditional food that
      is made by fermentation of highly salted [approximately 25 % (w/v)] shrimp in
      Korea. Cells were moderately halophilic, non-motile cocci or short rods that
      showed catalase- and oxidase-positive reactions. Growth of strain SJ5-4(T) was
      observed at 15-40  degrees C (optimum, 30  degrees C), at pH 6.0-9.5 (optimum, pH
      6.5-7.0) and in the presence of 1-17 % (w/v) NaCl (optimum, 6 %). The major
      cellular fatty acids of strain SJ5-4(T) were anteiso-C15 : 0, iso-C15 : 0,
      anteiso-C17 : 0, iso-C16 : 0 and C16 : 0. Phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylinositol, an unidentified phospholipid, three
      glycolipids and an unidentified lipid were detected as the polar lipids. Strain
      SJ5-4(T) belonged to the exceptionally small group of strains within the order
      Micrococcales that show a peptidoglycan cross-linked according to the A-type but
      containing 2,4-diaminobutyric acid. The G+C content of the genomic DNA was 61.8
      mol%. MK-7, MK-8 and MK-9 were detected as the isoprenoid quinones. Strain SJ5
      4(T) was most closely related to members of the genus Nesterenkonia, with 16S
      rRNA gene sequence similarities of 93.1-94.8 %. However, phylogenetic inference
      based on 16S rRNA gene sequences showed that strain SJ5-4(T) formed a phyletic
      lineage distinct from members of the genus Nesterenkonia within the family
      Micrococcaceae. On the basis of its phenotypic and molecular features, strain SJ5
      4(T) represents a novel genus and species of the family Micrococcaceae, for which
      the name Garicola koreensis gen. nov., sp. nov. is proposed. The type strain of
      Garicola koreensis is SJ5-4(T) ( = KACC 16909(T) = JCM 18572(T) = DSM 28238(T)). 

PMID- 25563924
TI  - Sinomonas humi sp. nov., an amylolytic actinobacterium isolated from mangrove
      forest soil.
AB  - Strain MUSC 117(T) was isolated from mangrove soil of the Tanjung Lumpur forest
      in Pahang, Malaysia. This bacterium was yellowish-white pigmented, Gram-staining
      positive, rod-coccus shaped and non-motile. On the basis of 16S rRNA gene
      sequence, strain MUSC 117(T) exhibited highest sequence similarity to Sinomonas
      atrocyanea DSM 20127(T) (98.0 %), Sinomonas albida LC13(T) (97.9 %) and Sinomonas
      soli CW 59(T) (97.8 %), and lower (<97.6 %) sequence similarity to other species
      of the genus Sinomonas. DNA-DNA hybridization experiments revealed a low level of
      DNA-DNA relatedness (less than 27 %) between strain MUSC 117(T) and closely
      related species. Chemotaxonomically, the peptidoglycan type was A3alpha,
      containing the amino acids lysine, serine, glycine, alanine, glutamic acid and
      muramic acid. The whole-cell sugars detected were rhamnose, ribose, glucose,
      galactose and a smaller amount of mannose. The polar lipids consisted of
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and five
      unidentified glycolipids. The major fatty acids (>10.0 %) of the cell membrane
      were anteiso-C15 : 0 (39.4 %), C18 : 1omega7c (17.7 %), anteiso-C17 : 0 (17.2 %)
      and iso-C16 : 0 (11.4 %). The predominant respiratory quinones detected were MK
      9(H2) and MK-9. The DNA G+C content was 67.3 mol%. A comparison of BOX-PCR
      fingerprints indicated that strain MUSC 117(T) represented a unique DNA profile.
      Results based on a polyphasic approach showed that strain MUSC 117(T) represents
      a novel species of the genus Sinomonas, for which the name Sinomonas humi sp.
      nov. is proposed. The type strain of Sinomonas humi sp. nov. is MUSC 117(T) ( =
      DSM 29362(T) = MCCC 1K00410(T) = NBRC 110653(T)). 

PMID- 25563925
TI  - Syntheses and cytotoxicity of (R)- and (S)-7-methoxycryptopleurine.
AB  - Two efficient protocols are described for the transformation of a key chiral
      homoallyllic sulfinamine intermediate in four steps into enantioenriched 7
      methoxycryptopleurine. While one of the protocols relied on a rhodium catalyzed
      linear hydroformylation process, the alternative approach was based on a ring
      closing metathesis from the corresponding N-allyl-sulfinamine. The cytotoxic
      evaluation of both enantiomers of the target compound demonstrated that the (R)
      compound is much more potent than its antipode against the four cancer cell lines
      examined. 

PMID- 25563926
TI  - Efficient estimation of contact probabilities from inter-bead distance
      distributions in simulated polymer chains.
AB  - The estimation of contact probabilities (CP) from conformations of simulated bead
      chain polymer models is a key step in methods that aim to elucidate the spatial
      organization of chromatin from analysis of experimentally determined contacts
      between different genomic loci. Although CPs can be estimated simply by counting
      contacts between beads in a sample of simulated chain conformations, reliable
      estimation of small CPs through this approach requires a large number of
      conformations, which can be computationally expensive to obtain. Here we describe
      an alternative computational method for estimating relatively small CPs without
      requiring large samples of chain conformations. In particular, we estimate the
      CPs from functional approximations to the cumulative distribution function (cdf)
      of the inter-bead distance for each pair of beads. These cdf approximations are
      obtained by fitting the extended generalized lambda distribution (EGLD) to inter
      bead distances determined from a sample of chain conformations, which are in turn
      generated by Monte Carlo simulations. We find that CPs estimated from fitted EGLD
      cdfs are significantly more accurate than CPs estimated using contact counts from
      samples of limited size, and are more precise with all sample sizes, permitting
      as much as a tenfold reduction in conformation sample size for chains of 200
      beads and samples smaller than 10(5) conformations. This method of CP estimation
      thus has potential to accelerate computational efforts to elucidate the spatial
      organization of chromatin. 

PMID- 25563927
TI  - A new class of rare earth tetrapyrrole sandwich complexes containing corrole and
      phthalocyanine macrocycles: synthesis, physicochemical characterization and X-ray
      analysis.
AB  - The first europium triple-decker tetrapyrrole with mixed corrole and
      phthalocyanine macrocycles was synthesized and characterized by spectroscopic and
      electrochemical methods. The molecular structure was characterized by single
      crystal X-ray diffraction and showed the corrole to be in the middle of the
      sandwich with phthalocyanine macrocycles at each extreme. 

PMID- 25563928
TI  - The toll of traffic-related fatalities in a metropolitan Italian area through the
      experience of the Department of Legal Medicine.
AB  - Despite the introduction of new traffic laws in Italy, traffic-related deaths are
      still a huge burden. The study presents data and medico-legal issues behind
      traffic deaths in Milan between 2001 and 2012 (1506 traffic-related deaths). Data
      were collected from the database of the Department of Legal Medicine: 79.4% males
      and 20.6% females (mean age 44.14). The target group concerned traumatic deaths
      as a consequence of the accident as well as deaths not directly related to an
      accident. Although 6.1% were non-traumatic deaths (cause of death unconnected to
      the accident, i.e. because of a heart attack, or when death occurred after
      survival and cause of death was not related certainly to the accident), multiple
      skeletal/visceral injuries were the main cause of death (57.9%), occurring in
      motorcyclists the most (63.7%). Injuries to the skull and brain were the second
      cause of death (25.9%). Victims were mostly males (79.4%) and drivers (77.6%).
      Fifty-five per cent were deaths on-scene, while 45% survived. Other variables
      were also considered: medications, medical history, and drugs/alcohol/smoke. A
      downward trend in traffic-related fatalities was evident, but the toll is still
      high. This study should be a glimpse at the actual situation, since it is
      indicative of a metropolitan area where autopsies are systematically performed. 

PMID- 25563929
TI  - Efficacy and pharmacokinetic evaluation of a novel anti-malarial compound (NP046)
      in a mouse model.
AB  - BACKGROUND: Even though malaria is a completely preventable and treatable
      disease, it remains a threat to human life and a burden to the global economy due
      to the emergence of multiple-drug resistant malaria parasites. According to the
      World Malaria Report 2013, in 2012 there were an estimated 207 million malaria
      cases and 627,000 deaths. Thus, the discovery and development of new, effective
      anti-malarial drugs are required. To achieve this goal, the Department of
      Chemistry at the University of the Free State has synthesized a number of novel
      amino-alkylated chalcones and analogues, which showed in vitro anti-malarial
      activity against both chloroquine-sensitive and chloroquine-resistant Plasmodium
      falciparum strains. The lead compound (NP046) was selected for a comprehensive
      pharmacokinetic (PK) and in vivo efficacy evaluation in a mouse model. METHODS:
      In vivo efficacy: Water solutions of NP046 were administered orally at 50 and 10
      mg/kg using oral gavage and IV at 5 and 1 mg/kg via the dorsal penile vein to
      Plasmodium berghei (ANKA strain) infected male C57BL/6 mice (n = 5), once a day
      for four days. Blood samples were collected via tail bleeding in tubes containing
      phosphate buffer saline (PBS) on day five to determine the % parasitaemia by flow
      cytometry.In vivo PK: NP046 solutions in water were administered orally (50 and
      10 mg/kg) and IV (5 mg/kg) to male C57BL/6 mice (n = 5). Blood samples were
      collected via tail bleeding into heparinized tubes and analysed using a validated
      LC-MS/MS assay. Data obtained from the concentration-time profile was evaluated
      using Summit PK software to determine the PK parameters of NP046. RESULTS: NP046
      inhibited parasite growth for the oral and IV groups. Better parasite growth
      inhibition was observed for the IV group. The PK evaluation of NP046 showed low
      oral bioavailability (3.2% and 6% at 50 mg/kg and 10 mg/kg dose, respectively and
      a moderate mean half-life ranging from 3.1 to 4.4 hours. CONCLUSION: Even though
      the oral bioavailability of NP046 is low, its percentage parasite growth
      inhibition is promising, but in order to improve the oral bioavailability,
      structure-activity-relationship (SAR) optimization studies are currently being
      conducted.

PMID- 25563930
TI  - Ubiquitous human 'master' origins of replication are encoded in the DNA sequence
      via a local enrichment in nucleosome excluding energy barriers.
AB  - As the elementary building block of eukaryotic chromatin, the nucleosome is at
      the heart of the compromise between the necessity of compacting DNA in the cell
      nucleus and the required accessibility to regulatory proteins. The recent
      availability of genome-wide experimental maps of nucleosome positions for many
      different organisms and cell types has provided an unprecedented opportunity to
      elucidate to what extent the DNA sequence conditions the primary structure of
      chromatin and in turn participates in the chromatin-mediated regulation of
      nuclear functions, such as gene expression and DNA replication. In this study, we
      use in vivo and in vitro genome-wide nucleosome occupancy data together with the
      set of nucleosome-free regions (NFRs) predicted by a physical model of nucleosome
      formation based on sequence-dependent bending properties of the DNA double-helix,
      to investigate the role of intrinsic nucleosome occupancy in the regulation of
      the replication spatio-temporal programme in human. We focus our analysis on the
      so-called replication U/N-domains that were shown to cover about half of the
      human genome in the germline (skew-N domains) as well as in embryonic stem cells,
      somatic and HeLa cells (mean replication timing U-domains). The 'master' origins
      of replication (MaOris) that border these megabase-sized U/N-domains were found
      to be specified by a few hundred kb wide regions that are hyper-sensitive to
      DNase I cleavage, hypomethylated, and enriched in epigenetic marks involved in
      transcription regulation, the hallmarks of localized open chromatin structures.
      Here we show that replication U/N-domain borders that are conserved in all
      considered cell lines have an environment highly enriched in nucleosome-excluding
      energy barriers, suggesting that these ubiquitous MaOris have been selected
      during evolution. In contrast, MaOris that are cell-type-specific are mainly
      regulated epigenetically and are no longer favoured by a local abundance of
      intrinsic NFRs encoded in the DNA sequence. At the smaller few hundred bp scale
      of gene promoters, CpG-rich promoters of housekeeping genes found nearby
      ubiquitous MaOris as well as CpG-poor promoters of tissue-specific genes found
      nearby cell-type-specific MaOris, both correspond to in vivo NFRs that are not
      coded as nucleosome-excluding-energy barriers. Whereas the former promoters are
      likely to correspond to high occupancy transcription factor binding regions, the
      latter are an illustration that gene regulation in human is typically cell-type
      specific. 

PMID- 25563931
TI  - Impacts of multiple stressors during the establishment of fouling assemblages.
AB  - Limited knowledge of the mechanisms through which multiple stressors affect
      communities and ecosystems limits capacity to predict their effects. Less clear
      is how stressors impact early colonization of newly available habitats due to
      scarcity of studies. The present study tested whether copper and freshwater input
      affect colonization of hard substrata independently or interactively and assessed
      differences in community respiration and total biomass among early stage
      assemblages which developed under different regimes of copper and freshwater
      input. While copper influenced effectively the colonization of individual
      species, freshwater effect was weak or null. Apart from a significant effect on
      total community composition, the interactive effect between stressors was weak
      and mainly driven by antagonistic interactions between copper and water flow.
      Total biomass and respiration of the community studied were not affected by
      stressors. These findings contradict the expectation that changes in community
      structure are likely to cause changes in functioning. 

PMID- 25563932
TI  - Change of geographical location from Germany (Bavaria) to USA (Arizona) and its
      effect on H-C-N-S stable isotopes in human hair.
AB  - To receive information about the duration of a person's stay abroad related to
      those questions in forensics, stable isotopes of H-C-N-S were analysed in beard
      hair samples from four young soldiers, who went from Furstenfeldbruck (Bavaria,
      Germany) to Phoenix (Arizona, USA) on the same date for their pilot training over
      a time period of 3 months. All study subjects were almost of the same age, had
      similar physical constitutions and stayed at the same military bases for the
      whole study period. However, the results showed considerable individual
      variabilities. In Arizona, hair delta(13)C increased by 2.30/00 (+/-0.6) and
      delta(34)S decreased by 1.80/00 (+/-1.2). No remarkable shifts of hair delta(15)N
      and delta(2)H were observed. Significant shifts of delta(13)C or delta(34)S in
      the shaved beard hair samples occurred 8 or 9 days after arrival in Arizona,
      respectively. The time lag to receive the isotope signals in hair due to US diet
      correspond to the growth period that hair needs to cover the distance of 2-3 mm
      from its root to the surface of the skin. This implies that isotopic changes due
      to the consumption of food and drinks were incorporated almost immediately into
      the hair protein. Consequently, if connected with an isotopic change of the diet,
      short-term stays for only a few days might be clearly recognizable within the
      first millimetres of a scalp hair strand which includes the hair roots.

PMID- 25563933
TI  - Impact of temperature on the ratio of initial emittable concentration to total
      concentration for formaldehyde in building materials: theoretical correlation and
      validation.
AB  - The initial emittable concentration (Cm,0) is a key parameter characterizing the
      emission behaviors of formaldehyde from building materials, which is highly
      dependent on temperature but has seldom been studied. Our previous study found
      that Cm,0 is much less than the total concentration (C0,total, used for labeling
      material in many standards) of formaldehyde. Because Cm,0 and not C0,total
      directly determines the actual emission behaviors, we need to determine the
      relationship between Cm,0 and C0,total so as to use Cm,0 as a more appropriate
      labeling index. By applying statistical physics theory, this paper derives a
      novel correlation between the emittable ratio (Cm,0/C0,total) and temperature.
      This correlation shows that the logarithm of the emittable ratio multiplied by
      power of 0.5 of temperature is linearly related to the reciprocal of temperature.
      Emissions tests for formaldehyde from a type of medium density fiberboard over
      the temperature range of 25.0-80.0  degrees C were performed to validate the
      correlation. Experimental results indicated that Cm,0 (or emittable ratio)
      increased significantly with increasing temperature, this increase being 14-fold
      from 25.0 to 80.0  degrees C. The correlation prediction agreed well with
      experiments, demonstrating its effectiveness in characterizing physical
      emissions. This study will be helpful for predicting/controlling the emission
      characteristics of pollutants at various temperatures.

PMID- 25563934
TI  - Exhaustive data mining comparison of the effects of low doses of ionizing
      radiation, formaldehyde and dioxins.
AB  - BACKGROUND: Ionizing radiation in low doses is the ubiquitous environmental
      factor with harmful stochastic effects. Formaldehyde is one of the most reactive
      household and industrial pollutants. Dioxins are persistent organic pollutants
      and most potent synthetic poisons effective even at trace concentrations.
      Environmental pollutants are capable of altering the expression of a variety of
      genes. To identify the similarities and differences in the effects of low-dose
      ionizing radiation, formaldehyde and dioxin on gene expression, we performed the
      bioinformatic analysis of all available published data. RESULTS: We found that
      that in addition to the common p53-, ATM- and MAPK-signaling stress response
      pathways, genes of cell cycle regulation and proinflammatory cytokines, the
      studied pollutants induce a variety of other molecular processes. CONCLUSIONS:
      The observed patterns provide new insights into the mechanisms of the adverse
      effects associated with these pollutants. They can also be useful in the
      development of new bio-sensing methods for detection of pollutants in the
      environment and combating the deleterious effects.

PMID- 25563936
TI  - A cysteamine-selective two-photon fluorescent probe for ratiometric bioimaging.
AB  - We report a two-photon fluorescent probe for ratiometric imaging of cysteamine in
      situ. This probe can detect the levels of endogenous cysteamine with statistical
      significance in live cells and brain hippocampal tissues, revealing that
      cysteamine is localized mainly in the perikaria of the pyramidal neurons and the
      granule cells. 

PMID- 25563935
TI  - A Duet for one.
AB  - This paper considers communication in terms of inference about the behaviour of
      others (and our own behaviour). It is based on the premise that our sensations
      are largely generated by other agents like ourselves. This means, we are trying
      to infer how our sensations are caused by others, while they are trying to infer
      our behaviour: for example, in the dialogue between two speakers. We suggest that
      the infinite regress induced by modelling another agent - who is modelling you -
      can be finessed if you both possess the same model. In other words, the
      sensations caused by others and oneself are generated by the same process. This
      leads to a view of communication based upon a narrative that is shared by agents
      who are exchanging sensory signals. Crucially, this narrative transcends agency -
      and simply involves intermittently attending to and attenuating sensory input.
      Attending to sensations enables the shared narrative to predict the sensations
      generated by another (i.e. to listen), while attenuating sensory input enables
      one to articulate the narrative (i.e. to speak). This produces a reciprocal
      exchange of sensory signals that, formally, induces a generalised synchrony
      between internal (neuronal) brain states generating predictions in both agents.
      We develop the arguments behind this perspective, using an active (Bayesian)
      inference framework and offer some simulations (of birdsong) as proof of
      principle. 

PMID- 25563937
TI  - Spatial tuning of acoustofluidic pressure nodes by altering net sonic velocity
      enables high-throughput, efficient cell sorting.
AB  - Particle sorting using acoustofluidics has enormous potential but widespread
      adoption has been limited by complex device designs and low throughput. Here, we
      report high-throughput separation of particles and T lymphocytes (600 MUL min(
      1)) by altering the net sonic velocity to reposition acoustic pressure nodes in a
      simple two-channel device. The approach is generalizable to other microfluidic
      platforms for rapid, high-throughput analysis. 

PMID- 25563938
TI  - One-pot synthesis of thermoplastic mixed paramylon esters using trifluoroacetic
      anhydride.
AB  - Mixed paramylon esters prepared from paramylon (a storage polysaccharide of
      Euglena), acetic acid, and a long-chain fatty acid by one-pot synthesis using
      trifluoroacetic anhydride as a promoter and solvent were shown to have
      thermoplasticity. Size exclusion chromatography indicated that the mixed
      paramylon esters had a weight average molecular weight of approximately 4.9
      6.7*10(5). Thermal analysis showed that these esters were stable in terms of the
      glass transition temperature (>90 degrees C) and 5% weight loss temperature (>320
      degrees C). The degree of substitution of the long alkyl chain group, a dominant
      factor determining thermoplasticity, was controlled by tuning the feed molar
      ratio of acetic acid and long-chain fatty acid to paramylon. These results
      implied that the one-pot synthesis is useful for preparing structurally-well
      defined thermoplastic mixed paramylon esters with high molecular weight.

PMID- 25563939
TI  - Structural changes of Salix miyabeana cellulose fibres during dilute-acid steam
      explosion: impact of reaction temperature and retention time.
AB  - Dilute-acid steam explosion of Salix miyabeana has been carried out to understand
      the effect of processing conditions, expressed through a severity factors (SFT),
      on the changes in cellulose fibre structures in a perspective of using these in
      polymer composites. This thermo-chemico-mechanical extraction leads to the
      isolation of cellulose fibres as observed by SEM images. Fibre length as well as
      length to diameter aspect ratios decreased with the severity of the treatment.
      Likewise, fibre whiteness diminished with an increasing severity factor, which
      could be a tangible effect of physical degradation. Variations in crystallinity
      seemed to be dependent upon the reaction temperature, generally decreasing with
      regards to retention time. Above a severity threshold, a structural
      disorganization was observed. Overall, dilute-acid steam explosion was shown to
      be a valuable cellulose extraction process that can provide a variety of fibre
      structures. 

PMID- 25563940
TI  - Synthesis of photoresponsive hybrid alginate hydrogel with photo-controlled
      release behavior.
AB  - A photoresponsive hybrid alginate hydrogel was successfully prepared by Ca(2+)
      mediated crosslinking reaction with a mixture of beta-cyclodextrin-grafted
      alginate (beta-CD-Alg) and diazobenzene-modified poly(ethylene glycol) (Az2-PEG).
      The water-soluble Az2-PEG exhibits efficient trans-to-cis isomerization of the
      terminal azobenzene moieties under UV-light irradiation and readily switched back
      to the initial trans state under visible light. Because of low affinity between
      beta-CD and cis-Az, the host-guest inclusion complex formed by beta-CD and trans
      Az gradually dissociates under UV-light exposure. Accordingly, the bulk gel
      exhibits substantial photo-induced transformation in gel morphology by the
      appearance of significant comb-like cavities. This photosensitive behavior
      accompanied by the structural degradation enables the rapid release of entrapped
      dye molecules under UV light stimulus. Moreover, an incident light with higher
      power and mild acidic environment are capable of accelerating the photo-triggered
      release, thus allowing the potential applications toward acute wound healing. 

PMID- 25563942
TI  - Native and structurally modified gum arabic: exploring the effect of the gum's
      microstructure in obtaining electroactive nanoparticles.
AB  - Electroactive nanoparticles combining gum arabic (GA) and polyaniline (PANI) were
      prepared by chemical synthesis. The gum consists of highly branched anionic
      polysaccharides with some protein content. GA was structurally modified by Smith
      controlled degradation, in order to reduce its degree of branching (GAD), aiming
      the elucidation of the relationship between the structure and the properties of
      complex polysaccharides. The modification was studied by SEC, GC-MS, (13)C NMR
      and colorimetric methods. GAD has lower molecular mass, lower degree of branching
      and lower uronic acid content. Besides it is enriched in galactose and protein
      when compared with GA. The obtained composites (GA-PANI and GAD-PANI) were
      thoroughly characterized. Although the use of both polysaccharides (GA and GAD)
      produced highly stable electroactive nanoparticles, the best combination of
      properties was achieved for GA-PANI. The sample GAD was not able to prevent the
      occurrence of crosslinking between PANI chains, possibly due to its lower
      microstructural complexity which diminishes the occurrence of hydrogen bonds
      between the polymers. 

PMID- 25563941
TI  - Beta-cyclodextrin polymer as a linker to fabricate ternary nanocomposites
      AuNPs/pATP-beta-CDP/rGO and their electrochemical application.
AB  - Based on the self-assembly strategy, beta-cyclodextrin polymer (beta-CDP) was
      used as a linker to connect reduced graphene oxide (rGO) and p-aminothiophenol
      (pATP). Then, pre-prepared gold nanoparticles (AuNPs) can self-assemble onto the
      surface of pATP-beta-CDP/rGO to obtain new ternary nanocomposites AuNPs/pATP-beta
      CDP/rGO. The amount or the density of AuNPs can be adjusted by changing the
      concentration of pATP. UV-vis and (1)H NMR spectra confirmed the formation of
      inclusion complex between pATP and beta-CDP. beta-CDP might improve the
      dispersity of rGO in aqueous and the surface property of rGO. AuNPs/pATP-beta
      CDP/rGO modified electrode displayed high electrochemical response toward a
      pesticide-imidacloprid (IDP). The enrichment capability and molecular recognition
      of beta-CDP and the catalytic property of AuNPs for IDP molecules synergistically
      promoted the electrochemical response of rGO modified electrode. Additionally,
      ternary nanocomposites exhibited the good electrocatalytic performance for oxygen
      reduction in O2-saturated 0.1M H2SO4 solution. The proposed synthesis strategy
      provided a facile, feasible and effective method for development of
      electrochemical sensors and Au-based catalysts for fuel cells.

PMID- 25563944
TI  - Studying the effects of laccase treatment in a softwood dissolving pulp:
      cellulose reactivity and crystallinity.
AB  - An enzymatic biobleaching sequence (LVAQPO) using a laccase from Trametes villosa
      in combination with violuric acid (VA) and then followed by a pressurized
      hydrogen peroxide treatment (PO) was developed and found to give high bleaching
      properties and meet dissolving pulp requirements: high brightness, low content of
      hemicellulose, satisfactory pulp reactivity, no significant cellulose degradation
      manifested by alpha-cellulose and HPLC, and brightness stability against moist
      heat ageing. The incorporation of a laccase-mediator system (LMS) to bleach
      sulphite pulps can be a good alternative to traditional bleaching processes since
      thermogravimetric analysis (TGA) showed that the laccase treatment prevented the
      adverse effect of hydrogen peroxide on fibre surface as observed during a
      conventional hydrogen peroxide bleaching treatment (PO). Although VA exhibited
      the best results in terms of bleaching properties, the performance of natural
      mediators, such as p-coumaric acid and syringaldehyde, was discussed in relation
      to changes in cellulose surface detected by TGA.

PMID- 25563943
TI  - Determination of molecular weight distributions in native and pretreated wood.
AB  - The analysis of native wood components by size-exclusion chromatography (SEC) is
      challenging. Isolation, derivatization and solubilization of wood polymers is
      required prior to the analysis. The present approach allowed the determination of
      molecular weight distributions of the carbohydrates and of lignin in native and
      processed woods, without preparative component isolation steps. For the first
      time a component selective SEC analysis of sawdust preparations was made possible
      by the combination of two selective derivatization methods, namely; ionic liquid
      assisted benzoylation of the carbohydrate fraction and acetobromination of the
      lignin in acetic acid media. These were optimized for wood samples. The developed
      method was thus used to examine changes in softwood samples after degradative
      mechanical and/or chemical treatments, such as ball milling, steam explosion,
      green liquor pulping, and chemical oxidation with 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone (DDQ). The methodology can also be applied to examine changes in
      molecular weight and lignin-carbohydrate linkages that occur during wood-based
      biorefinery operations, such as pretreatments, and enzymatic saccharification.

PMID- 25563945
TI  - Effect of rheological properties of dissolved cellulose/microfibrillated
      cellulose blend suspensions on film forming.
AB  - Enzymatically treated cellulose was dissolved in a NaOH/ZnO solvent system and
      mixed together with microfibrillated cellulose (MFC) in order to find the
      threshold in which MFC fibers form a percolation network within the dissolved
      cellulose solution and in order to improve the properties of regenerated
      cellulose films. In the aqueous state, correlations between the rheological
      properties of dissolved cellulose/MFC blend suspensions and MFC fiber
      concentrations were investigated and rationalized. In addition, rheological
      properties of diluted MFC suspensions were characterized and a correlation with
      NaOH concentration was found, thus partly explaining the flow properties of
      dissolved cellulose/MFC blend suspensions. Finally, based on results from Dynamic
      Mechanical Analysis (DMA), MFC addition had strengthening/plasticizing effect on
      regenerated cellulose films if low concentrations of MFC, below the percolation
      threshold (5.5-6 wt%, corresponding to 0.16-0.18 wt% of MFC in the blend
      suspensions), were used. 

PMID- 25563946
TI  - Establishment of an activated peroxide system for low-temperature cotton
      bleaching using N-[4-(triethylammoniomethyl)benzoyl]butyrolactam chloride.
AB  - Cotton bleaching is traditionally carried out in strongly alkaline solution of
      hydrogen peroxide (H2O2) at temperatures close to the boil. Such harsh processing
      conditions can result in extensive water and energy consumptions as well as
      severe chemical damage to textiles. In this study, an activated peroxide system
      was established for low-temperature cotton bleaching by incorporating a bleach
      activator, namely N-[4-(triethylammoniomethyl)benzoyl]butyrolactam chloride
      (TBBC) into an aqueous H2O2 solution. Experimental results showed that the TBBC
      activated peroxide system exhibited the most effective bleaching performance in a
      pH range of 6-8 which could be approximated by adding sodium bicarbonate
      (NaHCO3). The TBBC/H2O2/NaHCO3 system led to rapid bleaching of cotton at a
      temperature as low as 50 degrees C. In comparison with the hot alkaline peroxide
      bleaching system, the TBBC/H2O2/NaHCO3 system provided cotton fabric with an
      equivalent degree of whiteness, higher degree of polymerization, and slightly
      lower water absorbency. The new activated peroxide system may provide a more
      environmentally benign approach to cotton bleaching.

PMID- 25563947
TI  - Isosorbide, a green plasticizer for thermoplastic starch that does not
      retrogradate.
AB  - Isosorbide is a non-toxic biodegradable diol derived from bio-based feedstock. It
      can be used for preparing thermoplastic starch through a semi-industrial process
      of extrusion. Isosorbide allows some technological advantages with respect to
      classical plasticizers: namely, direct mixing with starch, energy savings for the
      low processing temperature required and lower water uptake. Indeed, maize starch
      was directly mixed with the solid plasticizer and direct fed in the main hopper
      of a co-rotating twin screw extruder. Starch plasticization was assessed by X-ray
      diffraction (XRD) and dynamic-mechanical analysis (DMTA). Oxygen permeability,
      water uptake and mechanical properties were measured at different relative
      humidity (R.H.) values. These three properties turned out to be highly depending
      on the R.H. No retrogradation and changing of the material properties were
      occurred from XRD and DMTA after 9 months. 

PMID- 25563948
TI  - Application of inulin in cheese as prebiotic, fat replacer and texturizer: a
      review.
AB  - Inulin is a food ingredient that belongs to a class of carbohydrates known as
      fructans. Nutritionally it has functional properties and health-promoting effects
      that include reduced calorie value, dietary fiber and prebiotic effects. Inulin
      is increasingly used in industrially processed dairy and non-dairy products
      because it is a bulking agent for use in fat replacement, textural modification
      and organoleptic improvement. Addition of inulin to different kinds of cheese can
      be beneficial in the manufacture of a reduced- or low-fat, texturized, symbiotic
      product. This paper gives an overview of some aspects of the microstructural,
      textural, rheological, prebiotic and sensorial effects of inulin incorporated in
      cheese as fat replacer, prebiotic and texture modifier.

PMID- 25563949
TI  - Optimization of ultrasound extraction of Alisma orientalis polysaccharides by
      response surface methodology and their antioxidant activities.
AB  - Rhizoma alismatis (the rhizome of Alisma orientalis) polysaccharides (RAP) have
      been reported to have a variety of important biological activities. However,
      effective extraction of RAP has been an unsolved issue. In this study, we used an
      ultrasound method for high yield extraction of RAP and optimized the conditions
      using the response surface methodology (RSM). Following multiple regression
      analyses of the experimental results, we applied the 3-D response surface and the
      contour plots to determine the optimal conditions, which were found to be
      ultrasound treatment at 76.1 degrees C for 75.2 min, and water to material ratio
      at 30.1 ml/g. Under such conditions, the yield was 6.90% which was much higher
      than traditional hot water extraction yield (3.41%). The fractionated RAPs
      following stepwise ethanol precipitation showed strong antioxidant activities.
      The results indicated that ultrasound extraction was a very effective method for
      the extraction of RAP and the polysaccharides could be explored as a potential
      antioxidant agent for use in medicine or functional food.

PMID- 25563950
TI  - Sustaining guest molecules on bio-surfaces by grafting the surfaces with
      cyclodextrins.
AB  - Grafting cyclodextrins (CDs) onto materials is an interesting approach to provide
      the remarkable ability of CDs to form an inclusion complex with various guest
      molecules onto other (bio)materials. Here we show the design, synthesis and
      characterization of "a ready to graft beta-CD", which is a cyclodextrinyl
      methacrylate (M-beta-CD), which will easily attach covalently to thiol-containing
      materials via a simple Michael thiol-ene click reaction under a biologically mild
      condition. Reacting M-beta-CD with soluble keratin, human hair and a mucin layer
      as model biomaterials, in the presence of either tris (2-carboxyethyl) phosphine
      or vitamin C, resulted in beta-CD-grafted keratin that displayed a controlled
      release of 8-anilino-1-naphthalenesulfonic acid, and both beta-CD-grafted-hair
      strands and beta-CD-grafted-mucin layers that effectively retained curcumin.
      Although this was demonstrated with beta-CD on these three biomaterials, this
      platform could theoretically equally be used with other CDs to give a different
      range of guest material complexation, and be able to be applied to other thiol
      containing materials.

PMID- 25563951
TI  - Nanogels based on alginic aldehyde and gelatin by inverse miniemulsion technique:
      synthesis and characterization.
AB  - Nanogels were developed from alginic aldehyde and gelatin by an inverse
      miniemulsion technique. Stable inverse miniemulsions were prepared by sonication
      of noncontinuous aqueous phase (mixture of alginic aldehyde and gelatin) in a
      continuous organic phase (Span 20 dissolved in cyclohexane). Cross-linking
      occurred between alginic aldehyde (AA) and gelatin (gel) in the presence of borax
      by Schiff's base reaction during the formation of inverse miniemulsion. The
      effects of surfactant (Span 20) concentration, volume of the aqueous phase and
      AA/gel weight ratio on the size of the alginic aldehyde-gelatin (AA-gel)
      nanoparticles were studied. Nanogels were characterized by DLS, FT-IR
      spectroscopy, TGA, SEM and TEM. DLS, TEM and SEM studies demonstrated nanosize
      and spherical morphology of the nanogels. Hemocompatibility and in vitro
      cytocompatibility analyses of the nanogels proved their nontoxicity. The results
      indicated the potential of the present nanogel system as a candidate for drug-
      and gene-delivery applications.

PMID- 25563952
TI  - Study on ternary low density polyethylene/linear low density
      polyethylene/thermoplastic starch blend films.
AB  - In this work, low-density polyethylene/linear low-density
      polyethylene/thermoplastic starch (LDPE/LLDPE/TPS) films are prepared with the
      aim of obtaining environmentally friendly materials containing high TPS content
      with required packaging properties. Blending of LDPE/LLDPE (70/30 wt/wt) with 5
      20 wt% of TPS and 3 wt% of PE-grafted maleic anhydride (PE-g-MA) is performed in
      a twin-screw extruder, followed by the blowing process. Differential scanning
      calorimetric results indicate starch has more pronounced effect on
      crystallization of LLDPE than LDPE. Scanning electron micrograph shows a fairly
      good dispersion of TPS in PE matrices. Fourier transfer infrared spectra confirm
      compatibility between polymers using PE-g-MA as the compatibilizer. Storage
      modulus, loss modulus and complex viscosity increase with incorporation of
      starch. Tensile strength and elongation-at-break decrease from 18 to 10.5 MPa and
      340 to 200%, respectively when TPS increases from 5 to 20%. However, the required
      mechanical properties for packaging applications are attained when 15 wt% starch
      is added, as specified in ASTM D4635. Finally 12% increase in water uptake is
      achieved with inclusion of 15 wt% starch.

PMID- 25563953
TI  - Preparation of linear maltodextrins using a hyperthermophilic amylopullulanase
      with cyclodextrin- and starch-hydrolysing activities.
AB  - A novel method for the preparation of linear maltodextrins from cyclodextrins and
      starch was proposed. To accomplish this process, an amylopullulanase from
      hyperthermophilic archaeon Caldivirga maquilingensis (CMApu) was characterized
      and used. CMApu with an estimated molecular mass of 62.7 kDa by SDS-PAGE had a
      maximal pullulan-hydrolysing activity at 100 degrees C and pH 5.0. It could also
      hydrolyse amylopectin (AP), starch, beta-CD and amylose (AM), in a decreasing
      order of relative activities from 88.96% to 57.17%. TLC and HPAEC analysis
      revealed that CMApu catalyzed the debranching and degrading reactions to produce
      linear malto-oligosaccharides (<= G8-G1) from G8-beta-CD and/or normal CDs,
      amylodextrins (DP6-96) from AM, and amylodextrins (DP1-76) from AP and potato
      starch. Our results showed that CMApu had a great potential for the industrial
      preparation of linear maltodextrins from normal starch instead of waxy starch,
      malto-oligosaccharides or sucrose. And the high optimal temperature of CMApu
      facilitated the simultaneous gelatinization and hydrolysis of cereal starch.

PMID- 25563954
TI  - Viscoelastic and mechanical properties of hyaluronan films and hydrogels modified
      by carbodiimide.
AB  - This study investigated an effect of different ways of the preparation of
      insoluble hyaluronan material on its mechanical and viscoelastic properties.
      Hyaluronan (NaHy) of molecular weight Mw=500,000 g mol(-1) was modified with N-(3
      dimethylaminopropyl-N'-ethylcarbodiimide hydrochloride (EDC) and N
      hydroxysuccinimide (NHS), to be able absorb liquid without changing its
      mechanical properties. The modified, water insoluble NaHy materials were prepared
      in different geometry; as modified films and modified cylinders with exact
      dimensions. The occurrence of modification was confirmed by FT-IR (Fourier
      transform infrared spectroscopy) and (1)H NMR (proton nuclear magnetic resonance)
      spectroscopy and swelling test. The determined mechanical and viscoelastic
      properties of unmodified and modified hyaluronan revealed the high dependency of
      elasticity changes depending on the gel processing method. Moreover, NaHy gels in
      the cylindrical form with the sponge-like structure predominant them as a
      convenient geometry for application in a humid environment.

PMID- 25563955
TI  - Stabilization of chitosan/hyaluronan colloidal polyelectrolyte complexes in
      physiological conditions.
AB  - Polyelectrolyte complexes (PECs) between hyaluronan (HYA) and chitosan were
      obtained by the one-shot addition of default amounts of polyanion to an excess of
      polycation. The impact of intrinsic parameters (degree of polymerization and
      degree of acetylation) and extrinsic parameters (charge mixing ratio, the
      concentration and pH of polyelectrolyte solutions) on particle sizes and
      polydispersity were investigated. The PECs maintained their colloidal stability
      when stored in water. To preserve the colloidal stability at physiological salt
      concentration and pH, biological nontoxic metallic Zn(II) was added either post
      or during the formation of the particles. Dynamic light scattering results showed
      the PEC particle sizes in phosphate buffer saline remained constant and displayed
      a good stability at room temperature for at least 35 days, irrespective of the
      stabilization process by Zn(II). These results open promising prospects for the
      zinc cation stabilized chitosan-HYA PECs as efficient and safe tools for drug
      delivery. 

PMID- 25563956
TI  - Structure-property relationships of carboxymethyl hydroxypropyl guar gum in water
      and a hyperentanglement parameter.
AB  - The viscoelastic properties of carboxymethyl hydroxypropyl guar gum (CMHPG) in
      aqueous solution were determined as function of concentration and of molecular
      weight, using SEC/MALLS/dRI and viscometry. The chain is more rigid as in native
      guar as was deduced from the molecular parameter in dilute solution.
      Superstructures are formed in moderately concentrated solutions as is shown from
      the comparison of steady state shear and small amplitude oscillatory shear (SAOS)
      experiments. The shear rate dependent viscosity of CMHPG can satisfactorily be
      described by the Carreau-Yasuda model with the rheological parameters (eta0,
      lambda0, n, b) obtained from the evaluation of viscosity data. A quantitative
      hyperentanglement parameter is introduced to account for the differences in
      responses in shear and SAOS experiments.

PMID- 25563957
TI  - Bamboo (Neosinocalamus affinis)-based thin film, a novel biomass material with
      high performances.
AB  - Exploration of biomass based materials to replace conventional petroleum based
      ones has been a trend in recent decades. In this work, bamboo (Neosinocalamus
      affinis) with abundant resources was used for the first time to prepare films in
      the presence of cellulose. The effects of weight ratio of bamboo/cellulose on the
      appearances and properties of the films were investigated. It was confirmed there
      existed strong interactions between bamboo and cellulose, which were favorable to
      formation of homogeneous structure of blend films. Particularly, the presence of
      bamboo could improve the surface hydrophobicity, water resistance and thermal
      stability of blend films, and the films possessed an excellent oxygen barrier
      property, compared with generally used commercial packaging films. The bamboo
      biomass, therefore, is successfully used to create a new film material with a
      good application prospect in the fields of packaging, coating, and food industry.

PMID- 25563958
TI  - Microencapsulation of alginate-immobilized bagasse with Lactobacillus rhamnosus
      NRRL 442: enhancement of survivability and thermotolerance.
AB  - The aim of this research was to enhance the survivability of Lactobacillus
      rhamnosus NRRL 442 against heat exposure via a combination of immobilization and
      microencapsulation processes using sugarcane bagasse (SB) and sodium alginate
      (NaA), respectively. The microcapsules were synthesized using different alginate
      concentration of 1, 2 and 3% and NaA:SB ratio of 1:0, 1:1 and 1:1.5. This
      beneficial step of probiotic immobilization before microencapsulation
      significantly enhanced microencapsulation efficiency and cell survivability after
      heat exposure of 90 degrees C for 30s. Interestingly, the microcapsule of SB
      immobilized probiotic could obtain protection from heat using microencapsulation
      of NaA concentration as low as 1%. SEM images illustrated the incorporation of
      immobilized L. rhamnosus within alginate matrices and its changes after heat
      exposure. FTIR spectra confirmed the change in functional bonding in the presence
      of sugarcane bagasse, probiotic and alginate. The results demonstrated a great
      potential in the synthesis of heat resistant microcapsules for probiotic. 

PMID- 25563960
TI  - Preparation and characterization of collagen/hydroxypropyl methylcellulose (HPMC)
      blend film.
AB  - This study aimed to prepare and characterize the collagen/HPMC blend film (1/1).
      Thermogravimetric analysis and differential scanning calorimetry were used to
      investigate the thermal properties of the film. Both thermal decomposition
      temperature and denaturation temperature of the blend film were higher than those
      of the collagen film due to the intermolecular hydrogen bonding interaction
      between collagen and HPMC, which was demonstrated by Fourier transform infrared
      spectroscopy. Additionally, the morphologies, mechanical properties and
      hydrophilicity of films were examined. The blend film exhibited a more
      homogeneous and compact structure compared with that of the collagen film, as
      observed from scanning electron microscopy and atomic force microscopy. The
      tensile strength, ultimate elongation and hydrophilicity of the blend film were
      superior to those of the pure collagen film. Furthermore, the introduction of
      polyethylene glycol 1500 had almost no influence on the thermal properties of the
      blend film but obviously improved its stretch-ability and smoothness. 

PMID- 25563959
TI  - New finishing possibilities for producing durable multifunctional cotton/wool and
      viscose/wool blended fabrics.
AB  - This research work focuses on the development of a one-bath functional finishing
      procedure for imparting durable multifunctional properties such as easy care,
      soft-hand, antibacterial and/or ultra violet (UV) protection to cotton/wool and
      viscose/wool blends using diverse finishing combinations and formulations. In
      this study finishing agents such as reactant resin, silicon softeners, 4
      hydroxybenzophenone, triclosan, and pigment colorant were selected using
      magnesium chloride/citric acid as a mixed catalyst and the pad-dry microwave
      fixation technique. The results reveal that enhancement in the imparted
      functional properties are governed by type of the finished substrate as well as
      nature and concentration of finishing formulation components. The finished
      fabrics still retained high level of functionalities even after 15 consecutive
      laundering. Surface morphology and composition of selected samples were
      investigated using scan electron microscope (SEM) and energy-dispersive X-ray
      spectroscopy (EDX) analysis. The mode of interactions was also investigated.
      Practical applications for multifunctionlization of cellulose/wool blended
      fabrics are possible using these sorts of proper finishing formulations and
      unique finishing application method. 

PMID- 25563961
TI  - Fabrication and characterization of nanofibrillated cellulose and its aerogels
      from natural pine needles.
AB  - To obtain the nanofibriled cellulose from natural pine needles, a combination of
      chemical pretreatments and subsequently ultrasonic treatments was employed for
      removing the hemicelluloses and lignins and splitting the bundled cellulose into
      pine needle nanofibers. Using SEM and diameter distribution method, it was
      confirmed that the obtained pine needle nanofibers had a narrow diameter from 30
      to 70 nm. The crystalline type of the pine needle nanofibers was the cellulose I
      type. The crystallinity reached 66.19%, which was increased by 7.61% as compared
      with the raw material pine needles. The TGA and DTG results showed that the
      degradation temperature of the nanofibers was increased to approximately 267 and
      352 degrees C compared with 221 and 343 degrees C of the raw material fibers,
      respectively. Furthermore, the highly flexible and ultralight pine needle
      nanofibers aerogels were prepared from the aqueous pine needle nanofibers
      solution using the freezing-drying technique. Aerogels were studied by SEM
      observation and nitrogen gas adsorption. The mechanical properties were measured
      in compression for aerogels. This study provides a new opportunity to fabricate
      novel nanomaterials from waste biomass materials, which is crucial for the fully
      utilizing of abundant biomass resources.

PMID- 25563962
TI  - Acacia gum as modifier of thermal stability, solubility and emulsifying
      properties of alpha-lactalbumin.
AB  - Protein-polysaccharide conjugates often display improved techno-functional
      properties when compared to their individual involved biomolecules. alpha
      Lactalbumin:acacia gum (alpha-la:AG) conjugates were prepared via Maillard
      reaction by the dry-heating method. Conjugate formation was confirmed using
      results of absorbance, o-phthalaldehyde test, sodium dodecyl sulfate
      polyacrilamide gel electrophoresis (SDS-PAGE) and size exclusion chromatography.
      Techno-functional properties (emulsifying characteristics, solubility, and
      thermal stability) were evaluated for alpha-la, alpha-la/AG mixtures and alpha
      la:AG conjugates. Conjugate thermal stability was improved compared to pure alpha
      la treated at the same conditions of conjugate formation. Response surface
      methodology was used to establish models to predict solubility and emulsifying
      activity as functions of the salt concentration, pH and reaction time. alpha
      la:AG conjugate solubility is affected in a complex manner by the three factors
      analyzed. Emulsifying activity index (EAI) of alpha-la is significantly affected
      by pH, while the alpha-la:AG EAI is affected by the three analyzed factors. Both
      solubility and EAI are maximized with pH 8.0, NaCl concentration of 0.3 mol L(-1)
      and two days of Maillard reaction.

PMID- 25563963
TI  - Ophiopogon polysaccharide liposome can enhance the non-specific and specific
      immune response in chickens.
AB  - The purpose of this study is to investigate the immune-enhancing activity of
      ophiopogon polysaccharide liposome (OPL). In non-specific immune response
      experiment, the phagocytosis and cytokines secretion of peritoneal macrophages in
      vitro and in vivo were performed. In specific immune response experiment, the
      activity of OPL was measured on chickens which were vaccinated with Newcastle
      disease (ND) vaccine and then challenged with ND virus at 49-old-day. The results
      showed that OPL could significantly promote the phagocytosis of macrophages and
      induce the secretion of IL-2 and IL-6 in vitro; OPL at high and medium doses
      could significantly improve the phagocytosic index, promote lymphocyte
      proliferation, increase the proportion of T lymphocyte subpopulations (CD4(+) and
      CD8(+)), enhance antibody titer and improve the protective rate in vivo.
      Moreover, its efficacy was significantly better than ophiopogon polysaccharide
      (OP). These results indicated that the immune-enhancing activity of OP was
      significantly improved after encapsulated with liposome. 

PMID- 25563965
TI  - Interfacial water screens the protein-induced transmembrane voltage.
AB  - Transmembrane proteins are crucial in cellular traffic, signal transduction, and
      energy storage in a form of transmembrane voltage. These proteins are stabilized
      by hydrophobic and hydrophilic interactions, in which cytoplasmic and exoplasmic
      water plays a special role. Water structural ordering generates the dipole
      potential that typically overcompensates for an intrinsic membrane-protein
      potential gradient, and thus it modifies and sustains an overall cellular
      electrostatics. Although the transmembrane voltage has been extensively studied,
      the dipole potential has attracted very little attention. Here, by using
      molecular dynamics, we examined water electrostatic response to the transmembrane
      charge, field, and potential asymmetry introduced by the presence of four
      integral membrane proteins: typical of inner (alpha-helix) and outer membrane
      (beta-barrel). In all cases, the protein presence introduces electrostatic
      directionality in the transmembrane dipole field and voltage. In particular,
      water generates a deep potential sink if strongly polar residues are densely
      packed on one side of bilayer, as frequently occurs in a selectivity filter of
      the K(+) channel. We also found that protein secondary structure is less
      important than the polar residue distribution along the protein channel. Our
      findings are relevant for understanding the driving force behind biomembrane
      conductivity: the ability of biological water to electrostatically screen the
      transmembrane voltage. 

PMID- 25563966
TI  - Subporphyrinato boron(III) hydrides.
AB  - Subporphyrinato boron(III) hydrides were prepared by reduction of subporphyrinato
      boron(III) methoxides with diisobutylaluminum hydride (DIBAL-H) in good yields.
      The authenticity of the B-H bond has been unambiguously confirmed by a (1)H NMR
      signal that appears as a broad quartet at -2.27 ppm with a large coupling
      constant with the central (11)B, characteristic B-H infrared stretching
      frequencies, and single crystal X-ray diffraction analysis. Red shifts in the
      corresponding absorption and fluorescence profiles are accounted for in terms of
      the electron-donating nature of the B-hydride. The hydridic character of
      subporphyrinato boron(III) hydrides has been demonstrated by the production of H2
      via reaction with water or HCl, and controlled reductions of aromatic aldehydes
      and imines in the presence of a catalytic amount of Ph3C[B(C6F5)4]. 

PMID- 25563964
TI  - New shell crosslinked micelles from dextran with hydrophobic end groups and their
      interaction with bioactive molecules.
AB  - Micelles formed in aqueous solution by dextran with hydrophobic (alkyl) end
      groups were stabilized through divinyl sulfone crosslinking of the dextran shell.
      The efficacy of the crosslinking reaction was influenced by the divinyl sulfone
      amount, the pH and micelle concentration. Crosslinked micelles with a moderate
      crosslinking degree were further functionalized by attachment of 10 and 17 moles%
      N-(2-hydroxypropyl)-N,N-dimethyl-N-benzylammonium chloride groups along the
      dextran chain. The size and shape of both crosslinked micelles and their cationic
      derivatives were analyzed by DLS and TEM. The prepared micelles were able to bind
      anionic diclofenac (60-370 mg/g), hydrophobic anionic indometacin (70-120 mg/g),
      and hydrophobic alpha-tocopherol (170-220 mg/g) or ergocalciferol (90-110 mg/g)
      by hydrophobic or/and electrostatic forces. The release experiments and the
      antioxidant activity of bound alpha-tocopherol highlighted the potential of the
      new nano-sized micelles mainly as carriers for prolonged and controlled delivery
      of hydrophobic drugs.

PMID- 25563967
TI  - The significance of water co-transport for sustaining transpirational water flow
      in plants: a quantitative approach.
AB  - In a recent Opinion paper, Wegner (Journal of Experimental Botany 65, 381-392,
      2014) adapts a concept developed for water flow in animal tissues to propose a
      model, which can explain the loading of water into the root xylem against a
      difference in water potential (Psi) between the xylem parenchyma cell (more
      negative Psi) and the xylem vessel (less negative Psi). In this model, the
      transport of water is energized through the co-transport of ions such as K(+) and
      Cl(-) through plasma membrane-located transporters. The emphasis of the model is
      on the thermodynamic feasibility of the co-transport mechanism per se. However,
      what is lacking is a quantitative evaluation of the energy input required at the
      organismal level to sustain such a co-transport mechanism in the face of
      considerable net (transpirational) flows of water through the system. Here, we
      use a ratio of 500 water molecules being co-transported for every pair of K(+)
      and Cl(-) ions, as proposed for the animal system, to calculate the energy
      required to sustain daytime and night-time transpirational water flow in barley
      plants through a water co-transport mechanism. We compare this energy with the
      total daily net input of energy through photosynthetic carbon assimilation. Water
      co-transport can facilitate the filling of xylem against a difference in Psi of
      1.0MPa and puts a minor drain on the energy budget of the plant. Based on these
      findings it cannot be excluded that water co-transport in plants contributes
      significantly to xylem filling during night-time and possibly also daytime
      transpiration. 

PMID- 25563968
TI  - Plant defence responses in oilseed rape MINELESS plants after attack by the
      cabbage moth Mamestra brassicae.
AB  - The Brassicaceae family is characterized by a unique defence mechanism known as
      the 'glucosinolate-myrosinase' system. When insect herbivores attack plant
      tissues, glucosinolates are hydrolysed by the enzyme myrosinase (EC 3.2.1.147)
      into a variety of degradation products, which can deter further herbivory. This
      process has been described as 'the mustard oil bomb'. Additionally, insect damage
      induces the production of glucosinolates, myrosinase, and other defences.
      Brassica napus seeds have been genetically modified to remove myrosinase
      containing myrosin cells. These plants are termed MINELESS because they lack
      myrosin cells, the so-called toxic mustard oil mines. Here, we examined the
      interaction between B. napus wild-type and MINELESS plants and the larvae of the
      cabbage moth Mamestra brassicae. No-choice feeding experiments showed that M.
      brassicae larvae gained less weight and showed stunted growth when feeding on
      MINELESS plants compared to feeding on wild-type plants. M. brassicae feeding
      didn't affect myrosinase activity in MINELESS plants, but did reduce it in wild
      type seedlings. M. brassicae feeding increased the levels of indol-3-yl-methyl, 1
      methoxy-indol-3-yl-methyl, and total glucosinolates in both wild-type and
      MINELESS seedlings. M. brassicae feeding affected the levels of glucosinolate
      hydrolysis products in both wild-type and MINELESS plants. Transcriptional
      analysis showed that 494 and 159 genes were differentially regulated after M.
      brassicae feeding on wild-type and MINELESS seedlings, respectively. Taken
      together, the outcomes are very interesting in terms of analysing the role of
      myrosin cells and the glucosinolate-myrosinase defence system in response to a
      generalist cabbage moth, suggesting that similar studies with other generalist or
      specialist insect herbivores, including above- and below-ground herbivores, would
      be useful. 

PMID- 25563969
TI  - Genome-wide survey of the seagrass Zostera muelleri suggests modification of the
      ethylene signalling network.
AB  - Seagrasses are flowering plants which grow fully submerged in the marine
      environment. They have evolved a range of adaptations to environmental challenges
      including light attenuation through water, the physical stress of wave action and
      tidal currents, high concentrations of salt, oxygen deficiency in marine
      sediment, and water-borne pollination. Although, seagrasses are a key stone
      species of the costal ecosystems, many questions regarding seagrass biology and
      evolution remain unanswered. Genome sequence data for the widespread Australian
      seagrass species Zostera muelleri were generated and the unassembled data were
      compared with the annotated genes of five sequenced plant species (Arabidopsis
      thaliana, Oryza sativa, Phoenix dactylifera, Musa acuminata, and Spirodela
      polyrhiza). Genes which are conserved between Z. muelleri and the five plant
      species were identified, together with genes that have been lost in Z. muelleri.
      The effect of gene loss on biological processes was assessed on the gene ontology
      classification level. Gene loss in Z. muelleri appears to influence some core
      biological processes such as ethylene biosynthesis. This study provides a
      foundation for further studies of seagrass evolution as well as the hormonal
      regulation of plant growth and development. 

PMID- 25563970
TI  - Carbon-limited fed-batch production of medium-chain-length polyhydroxyalkanoates
      by a phaZ-knockout strain of Pseudomonas putida KT2440.
AB  - A medium-chain-length poly-3-hydroxyalkanote (MCL-PHA) depolymerase knockout
      mutant of Pseudomonas putida KT2440 was produced by double homologous
      recombination. A carbon-limited shake-flask study confirmed that depolymerase
      activity was eliminated. Lysis of both mutant and wild-type strains occurred
      under these conditions. In carbon-limited, fed-batch culture, the yield of
      unsaturated monomers from unsaturated substrate averaged only 0.62 mol mol(-1)
      for the phaZ minus strain compared to 0.72 mol mol(-1) for the wild type. The
      mutant strain also produced more CO2 and less residual biomass from the same
      amount of carbon substrate. However, most results indicated that elimination of
      PHA depolymerase activity had little impact on the overall yield of biomass and
      PHA. 

PMID- 25563972
TI  - Hypertension modifies OPG, RANK, and RANKL expression during the dental socket
      bone healing process in spontaneously hypertensive rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the dental socket bone healing
      process by histomorphometric and immunohistochemical analysis of osteoprotegerin
      (OPG), receptor activator of nuclear factor-kappabeta (RANK), and receptor
      activator of nuclear factor-kappabeta ligand (RANKL) proteins in spontaneously
      hypertensive rats (SHR). MATERIALS AND METHODS: Under general anesthesia, 25
      Wistar rats and 25 SHRs underwent upper right incisor extraction. Rats were
      euthanized after 7, 14, 21, 28, or 42 days of dental extractions.
      Histomorphometric and immunohistochemical analyses of OPG, RANK, and RANKL
      proteins were performed. RESULTS: Histomorphometric results showed decreased bone
      healing and reduced bone trabecular thickness in SHRs. Immunohistochemical
      reactions showed intense RANKL and RANK immunolabeling at 14 and 28 postoperative
      days and mild OPG immunolabeling at 7, 14, and 21 days after surgery in SHRs.
      CONCLUSION: The results of this study show that RANK, RANKL, and OPG
      immunolabeling was altered in SHRs, and these results are associated with bone
      healing delay and decreased trabecular thickness in SHRs. CLINICAL RELEVANCE:
      Hypertension alters the expression of RANK, RANKL, and OPG and delays the socket
      bone healing process. These alterations could influence some dental procedures
      such as orthodontic treatment and implant placement.

PMID- 25563973
TI  - A simple small syringe suction drain system for septic arthritis of the finger.

PMID- 25563974
TI  - A survey of assessment and management of velopharyngeal incompetence (VPI) in the
      UK and Ireland.
AB  - A questionnaire designed to survey methods of assessment and management of
      velopharyngeal incompetence (VPI) was circulated to all surgical members of the
      Craniofacial Society of Great Britain and Ireland. 45 questionnaires were
      distributed yielding 30 respondents (66.6% response rate). 27 respondents
      performed surgery for both cleft and non-cleft forms of VPI. Multi-planar
      videofluroscopy and nasendoscopy were the most frequently used methods of
      assessing and diagnosing VPI. The most frequently utilised corrective surgical
      procedure was palatal re-repair, followed by the Hynes pharyngoplasty and the
      Furlow double opposing z-plasty technique. Orticochea and Jackson
      pharyngoplasties were less commonly performed. Splitting the palate during
      pharyngoplasty procedures was an inconsistent practice. 20 palatal surgeons
      referred patients to an otolaryngology specialist when tonsillectomy and/or
      adenoidectomy was indicated prior to their corrective palatal procedure. This was
      most frequently performed 3 months prior to palatal surgery. This survey
      identified normal patient speech as the criterion of success after correctional
      surgery for VPI. Assessment and management of VPI in Great Britain and Ireland is
      a highly varied practice. When a palatal procedure is indicated, surgical
      approaches are tailored to address each individual's pattern of velopharyngeal
      closure deficiency. The surgeons surveyed reported this as being most accurately
      demonstrated by direct nasendoscopic visualisation and dynamic multi-planar
      videofluoroscopic studies. 

PMID- 25563971
TI  - Comparative transcriptomic analysis reveals novel genes and regulatory mechanisms
      of Tetragenococcus halophilus in response to salt stress.
AB  - Tetragenococcus halophilus, a moderately halophilic Gram-positive bacterium, was
      isolated from Chinese style soy sauce. This species is a valuable resource for
      investigating salt tolerance mechanisms and improving salinity resistance in
      microorganisms. RNA-seq was used to sequence T. halophilus samples treated with 0
      M (T1), 1 M (T2), and 3.5 M NaCl (T3). Comparative transcriptomic analyses of the
      different treatments were performed using gene ontology and Kyoto encyclopedia of
      genes and genome. The comparison of T1 and T2 by RNA-seq revealed that genes
      involved in transcription, translation, membrane system, and division were highly
      up-regulated under optimum salt condition. The comparison of T2 and T3 showed
      that genes related to heat shock proteins or the ATP-binding cassette transport
      systems were significantly up-regulated under maximum-salt condition. In
      addition, a considerable proportion of the significantly differently expressed
      genes identified in this study are novel. These data provide a crucial resource
      that may determine specific responses to salt stress in T. halophilus. 

PMID- 25563975
TI  - Self-sensing porphysomes for fluorescence-guided photothermal therapy.
AB  - Porphysomes are highly quenched unilamellar porphyrin-lipid nanovesicles with
      structurally dependent photothermal properties. The high packing density of
      porphyrin molecules in the lipid bilayer enables their application in
      photothermal therapy, whereas the partial disruption of the porphysome structure
      over time restores the porphyrin fluorescence and enables the fluorescence-guided
      photothermal ablation. This conversion is a time-dependent process and cannot be
      easily followed using existing analytical techniques. Here we present the design
      of a novel self-sensing porphysome (FRETysomes) capable of fluorescently
      broadcasting its structural state through Forster resonance energy transfer. By
      doping in a near-infrared emitting fluorophore, it is possible to divert a small
      fraction of the absorbed energy toward fluorescence emission which provides
      information on whether the vesicle is intact or disrupted. Addition of
      bacteriopheophorbide-lipid into the vesicle bilayer as a fluorescence acceptor
      (0.5-7.5 mol %) yields a large separation of 100 nm between the absorption and
      fluorescence bands of the nanoparticle. Furthermore, a progressive increase in
      FRET efficiency (14.6-72.7%) is observed. Photothermal heating and serum
      stability in FRETysomes is comparable with the undoped porphysomes. The
      fluorescence arising from the energy transfer between the donor and acceptor dyes
      can be clearly visualized in vivo through hyperspectral imaging. By calculating
      the ratio between the acceptor and donor fluorescence, it is possible to
      determine the structural fate of the nanovesicles. We observe using this
      technique that tumor accumulation of structurally intact porphyrin-lipid
      nanovesicles persists at 24 and 48 h postinjection. The development of FRETysomes
      offers a unique and critical imaging tool for planning porphysome-enabled
      fluorescence-guided photothermal treatment, which maximizes light-induced thermal
      toxicity. 

PMID- 25563976
TI  - Enantioselective total synthesis of (-)-nardoaristolone B via a gold(I)-catalyzed
      oxidative cyclization.
AB  - The first enantioselective total synthesis of (-)-nardoaristolone B is
      accomplished by the implementation of an enantio- and diastereoselective
      copper(I)-catalyzed conjugate addition/enolate trapping sequence and a gold(I)
      catalyzed oxidative cyclization (intermolecular oxidant), employed for the first
      time in total synthesis. 

PMID- 25563977
TI  - Brain and Testis Accumulation of Regorafenib is Restricted by Breast Cancer
      Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1).
AB  - PURPOSE: Regorafenib is a novel multikinase inhibitor, currently approved for the
      treatment of metastasized colorectal cancer and advanced gastrointestinal stromal
      tumors. We investigated whether regorafenib is a substrate for the multidrug
      efflux transporters ABCG2 and ABCB1 and whether oral availability, brain and
      testis accumulation of regorafenib and its active metabolites are influenced by
      these transporters. METHODS: We used in vitro transport assays to assess human
      (h)ABCB1- or hABCG2- or murine (m)Abcg2-mediated active transport at high and low
      concentrations of regorafenib. To study the single and combined roles of Abcg2
      and Abcb1a/1b in oral regorafenib disposition and the impact of Cyp3a-mediated
      metabolism, we used appropriate knockout mouse strains. RESULTS: Regorafenib was
      transported well by mAbcg2 and hABCG2 and modestly by hABCB1 in vitro. Abcg2 and
      to a lesser extent Abcb1a/1b limited brain and testis accumulation of regorafenib
      and metabolite M2 (brain only) in mice. Regorafenib oral availability was not
      increased in Abcg2(-/-);Abcb1a/1b(-/-) mice. Up till 2 h, metabolite M5 was
      undetectable in plasma and organs. CONCLUSIONS: Brain and testis accumulation of
      regorafenib and brain accumulation of metabolite M2 are restricted by Abcg2 and
      Abcb1a/1b. Inhibition of these transporters may be of clinical relevance for
      patients with brain (micro)metastases positioned behind an intact blood-brain
      barrier.

PMID- 25563979
TI  - Biomechanics of pelvic organ prolapse.

PMID- 25563978
TI  - Investigation of the Physico-Chemical Properties that Enable Co-Formulation of
      Basal Insulin Degludec with Fast-Acting Insulin Aspart.
AB  - PURPOSE: To study the self-association states of insulin degludec and insulin
      aspart alone and combined in pharmaceutical formulation and under conditions
      simulating the subcutaneous depot. METHODS: Formulations were made of 0.6 mM
      degludec at 3 and 5 Zn/6 insulin monomers, and 0.6 mM aspart (2 Zn/6 insulin
      monomers). Self-association was assessed using size-exclusion chromatography
      (SEC) monitored by UV and orthogonal reverse-phase chromatography. RESULTS:
      Simulating pharmaceutical formulation, degludec eluted as dihexamers, whereas
      aspart eluted as hexamers and monomers. Combining degludec at low zinc with
      aspart increased dihexamer content, indicating hybrid hexamer formation. At high
      zinc concentration, however, there was no evidence of this. Simulating the
      subcutaneous depot by removing preservative, degludec eluted as multihexamers and
      aspart as monomers. Aspart was incorporated into the multihexamer structures when
      combined with degludec at low zinc, but there was no such interaction with high
      zinc degludec. SEC using progressively diluted concentrations of phenol and m
      cresol showed that dissociation of aspart into monomers occurs before the
      formation of degludec multihexamers. CONCLUSION: Insulins degludec and aspart can
      be combined without forming hybrid hexamers, but this combinability is dependent
      on zinc and preservative concentration, and requires that degludec is fully
      dihexameric before addition of aspart.

PMID- 25563980
TI  - Tumor microenvironment: a mechanical force link.

PMID- 25563981
TI  - Genetic basis and biotechnological manipulation of sexual dimorphism and sex
      determination in fish.
AB  - Aquaculture has made an enormous contribution to the world food production,
      especially to the sustainable supply of animal proteins. The utility of diverse
      reproduction strategies in fish, such as the exploiting use of unisexual
      gynogenesis, has created a typical case of fish genetic breeding. A number of
      fish species show substantial sexual dimorphism that is closely linked to
      multiple economic traits including growth rate and body size, and the efficient
      development of sex-linked genetic markers and sex control biotechnologies has
      provided significant approaches to increase the production and value for
      commercial purposes. Along with the rapid development of genomics and molecular
      genetic techniques, the genetic basis of sexual dimorphism has been gradually
      deciphered, and great progress has been made in the mechanisms of fish sex
      determination and identification of sex-determining genes. This review summarizes
      the progress to provide some directive and objective thinking for further
      research in this field. 

PMID- 25563982
TI  - Multiscale modelling of nucleosome core particle aggregation.
AB  - The nucleosome core particle (NCP) is the basic building block of chromatin.
      Under the influence of multivalent cations, isolated mononucleosomes exhibit a
      rich phase behaviour forming various columnar phases with characteristic NCP-NCP
      stacking. NCP stacking is also a regular element of chromatin structure in vivo.
      Understanding the mechanism of nucleosome stacking and the conditions leading to
      self-assembly of NCPs is still incomplete. Due to the complexity of the system
      and the need to describe electrostatics properly by including the explicit mobile
      ions, novel modelling approaches based on coarse-grained (CG) methods at the
      multiscale level becomes a necessity. In this work we present a multiscale CG
      computer simulation approach to modelling interactions and self-assembly of
      solutions of NCPs induced by the presence of multivalent cations. Starting from
      continuum simulations including explicit three-valent cobalt(III)hexammine
      (CoHex(3+)) counterions and 20 NCPs, based on a previously developed advanced CG
      NCP model with one bead per amino acid and five beads per two DNA base pair unit
      (Fan et al 2013 PLoS One 8 e54228), we use the inverse Monte Carlo method to
      calculate effective interaction potentials for a 'super-CG' NCP model consisting
      of seven beads for each NCP. These interaction potentials are used in large-scale
      simulations of up to 5000 NCPs, modelling self-assembly induced by CoHex(3+). The
      systems of 'super-CG' NCPs form a single large cluster of stacked NCPs without
      long-range order in agreement with experimental data for NCPs precipitated by the
      three-valent polyamine, spermidine(3+). 

PMID- 25563983
TI  - Weight gain, overweight and obesity in solid organ transplantation--a study
      protocol for a systematic literature review.
AB  - BACKGROUND: Overweight and obesity, which have a substantial impact on health in
      the general population, have similar prevalence in solid organ transplant
      recipients but carry even more serious ramifications. As this group's use of
      immunosuppressive medication increases the risk for comorbidities, e.g. metabolic
      syndrome and cardiovascular disease, the prevention of additional risk factors is
      vital. This systematic review will be the first to summarize the issue of weight
      gain, overweight and obesity concurrently within and across solid organ
      transplantation. The three research questions relating to solid organ
      transplantation are the following: (1) What are the prevalence and evolution of
      overweight and obesity from pre- to post-transplant?; (2) Which pre- and post
      transplant risk factors are associated with post-transplant weight gain,
      overweight or obesity? and (3) Which post-transplant patient outcomes and
      comorbidities are associated with pre- and post-transplant weight gain,
      overweight and obesity? METHODS/DESIGN: MEDLINE via PubMed, The Cochrane Library,
      Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO and Excerpta
      Medica DataBase (EMBASE) will be searched for original quantitative studies in
      adult liver, heart, lung or kidney transplant patients. Topics of interest will
      be the prevalence and evolution of overweight and obesity over time, risk factors
      associated with changes in weight or body mass index (BMI), overweight and
      obesity, and the relationship of weight or BMI with post-transplant outcomes and
      comorbidities. Screening of titles and abstracts, full-text reading and data
      extraction will be divided between three researchers. Researchers will cross
      check one another's screening decisions for random samples of studies to adhere
      as closely as possible to the recommendations of The Cochrane Collaboration. For
      quality assessment, a purpose-adapted 19-item instrument will be used. Effect
      sizes will be calculated for relationships investigated in a minimum of five
      studies. Random effects meta-analysis with moderator analyses will be conducted
      if applicable. DISCUSSION: This systematic review will comprehensively synthesize
      the existing evidence concerning weight gain, overweight and obesity in solid
      organ transplantation in view of magnitude, influencing factors and associations
      with patient outcomes and comorbidities. The results can fuel the development of
      interventions to prevent weight gain in the solid organ transplant population.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009151.

PMID- 25563984
TI  - Whiteflies glycosylate salicylic acid and secrete the conjugate via their
      honeydew.
AB  - During insect feeding, a complex interaction takes place at the feeding site,
      with plants deciphering molecular information associated with the feeding
      herbivore, resulting in the upregulation of the appropriate defenses, and the
      herbivore avoiding or preventing these defenses from taking effect. Whiteflies
      can feed on plants without causing significant damage to mesophyll cells, making
      their detection extra challenging for the plant. However, whiteflies secrete
      honeydew that ends up on the plant surface at the feeding site and on distal
      plant parts below the feeding site. We reasoned that this honeydew, since it is
      largely of plant origin, may contain molecular information that alerts the plant,
      and we focused on the defense hormone salicylic acid (SA). First, we analyzed
      phloem sap from tomato plants, on which the whiteflies are feeding, and found
      that it contained salicylic acid (SA). Subsequently, we determined that in
      honeydew more than 80% of SA was converted to its glycoside (SAG). When
      whiteflies were allowed to feed from an artificial diet spiked with labeled SA,
      labeled SAG also was produced. However, manually depositing honeydew on undamaged
      plants resulted still in a significant increase in endogenous free SA.
      Accordingly, transcript levels of PR1a, an SA marker gene, increased whereas
      those of PI-II, a jasmonate marker gene, decreased. Our results indicate that
      whiteflies manipulate the SA levels within their secretions, thus influencing the
      defense responses in those plant parts that come into contact with honeydew.

PMID- 25563985
TI  - The influence of the microbiota on the immune response to transplantation.
AB  - PURPOSE OF REVIEW: In the past decade, appreciation of the important effects of
      commensal microbes on immunity has grown exponentially. The effect of the
      microbiota on transplantation has only recently begun to be explored; however,
      our understanding of the mechanistic details of host-microbe interactions is
      still lacking. RECENT FINDINGS: It has become clear that transplantation is
      associated with changes in the microbiota in many different settings, although
      what clinical events and therapeutic interventions contribute to these changes
      remains to be parsed out. Research groups have begun to identify associations
      between specific communities of organisms and transplant outcomes, but it remains
      to be established whether microbial changes precede or follow transplant
      rejection episodes. Finally, results from continuing exploration of basic
      mechanisms by which microbial communities affect innate and adaptive immunity in
      various animal models of disease continue to inform research on the microbiota's
      effects on immune responses against transplanted organs. SUMMARY: Commensal
      microbes may alter immune responses to organ transplantation, but direct
      experiments are only beginning in the field to identify species and immune
      pathways responsible for these putative effects.

PMID- 25563986
TI  - Innate immunity for better or worse govern the allograft response.
AB  - PURPOSE OF REVIEW: To update knowledge concerning the cause and consequences of
      the detrimental forms of innate immunity that inevitably occurs in peritransplant
      period tissue and cellular transplants. In addition, we review the information
      that a newly discovered, engraftment-promoting, and tolerance-inducing macrophage
      population is identified and characterized. RECENT FINDINGS: The allograft
      response mounted by adaptive immune cells is shaped by innate immunity. The early
      allograft response is uniquely intense as a result of activation of the innate
      immune response created by ischemia reperfusion injury in organ transplants,
      delayed revascularization of cell transplants, and hypoxia. Inflammation is
      created by both cellular 'debris' and cytokines. However, a newly discovered
      prominent, albeit fragile, tissue-resident, noninvasive, and immunoregulatory
      macrophage promotes engraftment and tolerance. The role of intracellular 'debris'
      as well as inflammation in evoking detrimental rejection-provoking peritransplant
      inflammation is emphasized as well as characterization of a prominent and highly
      immunoregulatory albeit fragile macrophage population that is tissue-resident and
      does not circulate is characterized. SUMMARY: Opportunity lies in the ability to
      rein in detrimental peri-transplant inflammation and in the ability to promote
      the longevity of a subpopulation of highly potent tissue-resident
      immunoregulatory macrophages.

PMID- 25563989
TI  - MicroRNAs as master regulators of immune responses in transplant recipients.
AB  - PURPOSE OF REVIEW: MicroRNAs (miRNAs) have emerged as highly evolutionarily
      conserved moieties that have very selective gene-regulatory functions. miRNAs are
      being researched for their use as potential biomarkers for diagnostics, routine
      prognostics as well as selective therapeutics in cancer, infectious diseases,
      autoimmune disorders and transplantation. This review summarizes how immune
      regulation by miRNAs affects the outcome of transplantation. RECENT FINDINGS:
      Many miRNAs have been identified as selective markers for specific disease states
      and transplant conditions in the past two decades. In this review, we will
      discuss the recent advances and some seminal discoveries in miRNA research and
      their role as immune regulators in transplantation. Lastly, we will highlight the
      ongoing clinical trials for miRNA-based therapeutics for clinical applications
      and present our opinion on the future of miRNA-based diagnostics and
      therapeutics. SUMMARY: miRNA-based diagnosis is a fast-moving field with new
      miRNA signatures being identified each day. Recent advances have also been
      successful at taking a few of these miRNAs to clinical trials for therapeutic
      interventions.

PMID- 25563988
TI  - T-cell energy metabolism as a controller of cell fate in transplantation.
AB  - PURPOSE OF REVIEW: To highlight some of the recent developments in the novel
      field of immunometabolism and the therapeutic potential of the many regulatory
      components of this immunometabolic network for transplantation. RECENT FINDINGS:
      In response to cytokines, changes in nutrients, and other alterations in the
      local milieu, immune cells are capable of changing their internal metabolic
      pathways to meet their energy demands. Recent studies demonstrate that activated
      T effectors (Th1 and Th17) are supported by aerobic glycolysis, whereas
      regulatory T cells and CD8 memory T cells favor fatty acid oxidation and lipid
      biosynthesis through mitochondrial oxidative phosphorylation. These bioenergetic
      processes are dependent upon the activation of metabolic sensors such as
      mammalian target of rapamycin and AMP-activated protein kinase, respectively,
      indicating that the cross-talk between immunity and metabolism can shape the fate
      and function of immune cells. Finally, exciting new studies suggest that
      differences in the bioenergetic mechanisms within the various immune subsets may
      selectively be exploited for regulating the immune responses. SUMMARY: In this
      review, we will discuss the metabolic signatures adopted by various immune cells
      during tolerance versus immunity and the promising avenues that can be modulated
      by targeting metabolic pathways with either nutrition or pharmacological
      intervention for establishing long-term transplantation tolerance.

PMID- 25563987
TI  - Chronic allograft rejection: a fresh look.
AB  - PURPOSE OF REVIEW: New developments suggest that the graft itself and molecules
      expressed within the graft microenvironment dictate the phenotype and evolution
      of chronic rejection. RECENT FINDINGS: Once ischemia-reperfusion injury, cellular
      and humoral immune responses target the microvasculature, the associated local
      tissue hypoxia results in hypoxia-inducible factor 1alpha-dependent expression of
      pro-inflammatory and proangiogenic growth factors including vascular endothelial
      growth factor (VEGF) as a physiological response to injury. Local expression of
      VEGF can promote the recruitment of alloimune T cells into the graft. mTOR/Akt
      signaling within endothelial cells regulates cytokine- and alloantibody-induced
      activation and proliferation and their proinflammatory phenotype. Inhibition of
      mTOR and/or Akt results in an anti-inflammatory phenotype and enables the
      expression of coinhibitory molecules that limit local T cell reactivation and
      promotes immunoregulation. Semaphorin family molecules may bind to neuropilin-1
      on regulatory T cell subsets to stabilize functional responses. Ligation of
      neuropilin-1 on Tregs also inhibits Akt-induced responses suggesting common theme
      for enhancing local immunoregulation and long-term graft survival. SUMMARY:
      Events within the graft initiated by mTOR/Akt-induced signaling promote the
      development of chronic rejection. Semaphorin-neuropilin biology represents a
      novel avenue for targeting this biology and warrants further investigation.

PMID- 25563990
TI  - T-cell exhaustion in allograft rejection and tolerance.
AB  - PURPOSE OF REVIEW: The role of T-cell exhaustion in the failure of clearance of
      viral infections and tumors is well established. There are several ongoing trials
      to reverse T-cell exhaustion for treatment of chronic viral infections and
      tumors. The mechanisms leading to T-cell exhaustion and its role in
      transplantation, however, are only beginning to be appreciated and are the focus
      of the present review. RECENT FINDINGS: Exhausted T cells exhibit a distinct
      molecular profile reflecting combinatorial mechanisms involving the interaction
      of multiple transcription factors important in control of cell metabolism,
      acquisition of effector function and memory capacity. Change of
      microenvironmental cues and limiting leukocyte recruitment can modulate T-cell
      exhaustion. Impaired leukocyte recruitment induces T-cell exhaustion and prevents
      allograft rejection. SUMMARY: Preventing or reversing T-cell exhaustion may lead
      to prevention of transplant tolerance or triggering of rejection; therefore,
      caution should be exercised in the use of agents blocking inhibitory receptors
      for the treatment of chronic viral infections or tumors in transplant recipients.
      Further definition of the role of T-cell exhaustion in clinical transplantation
      and an understanding of the mechanisms of induction of T-cell exhaustion are
      needed to develop strategies for preventing allograft rejection and induction of
      tolerance.

PMID- 25563991
TI  - New insights into T-cell cosignaling in allograft rejection and survival.
AB  - PURPOSE OF REVIEW: Stimulatory and inhibitory receptor signaling (cosignaling) on
      T cells is a critical component of T-cell responses that mediate graft rejection.
      The blockade of cosignaling pathways is an attractive strategy for preventing
      allogeneic T-cell responses. Here, we review the new studies that provide
      critical insight into the well studied CD28-CTLA-4 and CD40-CD40L cosignaling
      pathways, as well as the identification of novel cosignaling receptors that play
      a role in allogeneic T-cell responses. RECENT FINDINGS: Recently, it has been
      appreciated that the CD28-CTLA-4 pathway has unique roles on specific T-cell
      subsets, particularly on forkhead box P3 (FoxP3)+ regulatory T cell (Treg) and T
      helper 17 (Th17) cells. New insight has been provided into the mechanism by which
      CD40-CD154 blockade elicits FoxP3+ Treg conversion and memory T cells elicit CD40
      independent alloantibody responses. Finally, several novel cosignaling pathways
      have been demonstrated to be important to graft-specific T cells, including
      CD160, signaling lymphocytic activation molecule family member 2B4, T-cell Ig
      mucin 4, and the Notch receptor. SUMMARY: Recent work has provided more granular
      understanding of the CD28-CTLA-4 and CD40-CD154 pathways on T-cell subsets, and
      provided important insight into the generation and maintenance of FoxP3+ Treg.
      This information, as well as the characterization of novel transplantation
      relevant cosignaling pathways, has implications for the modulation of
      alloreactive T-cell responses.

PMID- 25563993
TI  - Novel biomarkers and functional assays to monitor cell-therapy-induced tolerance
      in organ transplantation.
AB  - PURPOSE OF REVIEW: Cell-based immunotherapy offers a novel approach to minimize
      the need for immunosuppressive drugs and to promote a state of immunological
      tolerance to a transplanted organ. We review the most promising biomarkers and
      functional assays able to identify patients tolerant to their graft. Such a
      signature of tolerance is essential in the assessment of the efficacy with which
      trials of cellular therapies promote immunoregulation and minimize graft
      rejection. RECENT FINDINGS: A multitude of novel cellular therapies have entered
      early-phase clinical trials in solid-organ transplant patients. Recent
      multicentre collaborations have enabled the determination of distinct tolerance
      profiles for both liver and kidney transplant recipients. These have been shown
      to be highly predictive of tolerance in certain settings and show utility in
      identifying patients in whom immunosuppressive drugs can be weaned or
      discontinued. SUMMARY: In order to become a viable treatment option in solid
      organ transplantation, the latest large, multicentre clinical trials of cellular
      therapies must utilize, validate and discover the biomarkers with the capacity to
      reliably identify a signature of immune tolerance.

PMID- 25563994
TI  - Mesenchymal stromal cells for prevention and treatment of graft-versus-host
      disease: successes and hurdles.
AB  - PURPOSE OF REVIEW: The aim of the present review was to give a critical opinion
      on the use of mesenchymal stromal cells (MSCs) to treat or to prevent graft
      versus-host disease (GVHD). RECENT FINDINGS: The first part includes a summary of
      the many clinical trials published so far either to prevent or to treat GVHD in
      recipients of haematopoietic stem cell transplantation. We discuss in more detail
      a comparison in a subgroup of studies, including our own clinical work, which
      have in common the use of the platelet lysate to expand the MSCs from bone marrow
      origin.In the second part, we describe a few crucial elements of the biology of
      the GVHD and the biology of the MSCs themselves, showing their possible role in
      the immune modulation and in the inflammation in several in-vivo experimental
      models. SUMMARY: The complexity of the clinical condition that is the object of
      the trials and the paucity of information on the mechanisms of action in vivo of
      MSCs at different anatomical sites and in different times of the development of
      the disease preclude at the moment the identification of a strong rationale for
      MSC therapeutic schedule. Moreover, the typical development of GVHD requires
      different time points of clinical evaluation than those previously generally
      utilized in studies conducted on MSCs.

PMID- 25563992
TI  - Hematopoietic stem cell infusion/transplantation for induction of allograft
      tolerance.
AB  - PURPOSE OF REVIEW: The present review updates the current status of basic,
      preclinical, and clinical research on donor hematopoietic stem cell infusion for
      allograft tolerance induction. RECENT FINDINGS: Recent basic studies in mice
      provide evidence of significant involvement of both central deletional and
      peripheral regulatory mechanisms in induction and maintenance of allograft
      tolerance effected through a mixed chimerism approach with donor hematopoietic
      stem cell infusion. The presence of heterologous memory T cells in primates
      hampers the induction of persistent chimerism. Durable mixed chimerism, however,
      now has been recently induced in inbred major histocompatibility complex
      mismatched swine, resulting in tolerance of vascularized composite tissue
      allografts. In clinical transplantation, allograft tolerance has been achieved in
      human leukocyte antigen-mismatched kidney transplantation after the induction of
      transient mixed chimerism or persistent full donor chimerism. SUMMARY: Tolerance
      induction in clinical kidney transplantation has been achieved by donor
      hematopoietic stem cell infusion. Improving the consistency and safety of
      tolerance induction and extending successful protocols to other organs, and to
      organs from deceased donors, are critical next steps to bringing tolerance to a
      wider range of clinical applications.

PMID- 25563996
TI  - Simultaneous transplantation of the living donor kidney and deceased donor
      pancreas and other transplant options for diabetic and uremic patients.
AB  - PURPOSE OF REVIEW: Solitary deceased donor kidney and simultaneous pancreas and
      kidney (SPK) transplantation are the two most common transplant procedures
      performed for patients with diabetes and uremia, vastly outnumbering all other
      organ replacement options. Given the improvement in outcomes for solitary
      pancreas transplantation, the higher mortality for diabetic patients on the
      waiting list, and the growing shortage of organs (particularly kidneys) for
      transplantation, the use of living donors for this complex patient population
      should be more common. RECENT FINDINGS: Yet, despite some clear advantages,
      sequential pancreas after live donor kidney transplant and especially the
      combined procedure, simultaneous pancreas (from a deceased donor) and living
      donor kidney transplantation are relatively uncommon. SUMMARY: Possible reasons
      for the infrequent use of these options and methods for increasing the use of
      living donor kidneys for the diabetic and uremic patient are presented.

PMID- 25563995
TI  - Mesenchymal stromal cells to control donor-specific memory T cells in solid organ
      transplantation.
AB  - PURPOSE OF REVIEW: Mesenchymal stromal cells (MSCs) represent a promising cell
      therapy to promote transplant tolerance, as they influence many cells involved in
      immune response. Herein, we review recent evidence on the ability of MSCs to
      inhibit antigen-induced memory T cell response in vitro and in preclinical
      studies as well as immunological studies in kidney transplant recipients
      highlighting the effects of MSC therapy on memory CD8 T-cell proliferation and
      function. RECENT FINDINGS: MSCs are able to inhibit in-vitro proliferation and
      effector functions of memory T cells in response to auto-antigen and allo-antigen
      stimulation. MSC infusion in animal transplant models resulted in a skew of the
      balance between regulatory T cells and effector/memory T cells towards a pro
      tolerogenic profile. MSC in clinical transplantation is in its infancy and
      limited numbers of clinical studies have performed immunomonitoring of MSC
      treated patients. However, available data support the capability of MSCs to
      control effector/memory CD8 T-cell proliferation and donor-specific CD8 T-cell
      function long lasting in kidney transplant setting. SUMMARY: Recent studies of
      MSCs in kidney transplantation highlight the anticipated add-on value of the
      immunomodulatory properties of bone marrow derived MSCs in persistently
      inhibiting donor-specific effector/memory CD8 T cells, an effect not shared by
      the current immunosuppressive drugs.

PMID- 25563997
TI  - Pancreas after kidney transplantation: why is the most logical option the least
      popular?
AB  - PURPOSE OF REVIEW: Despite recent improvements in outcomes for pancreas
      transplantation in general, including graft survival following pancreas after
      kidney (PAK) transplantation, there has been a consistent decline in the number
      of PAK transplants performed in the USA. The purpose of the present review is to
      analyze the advantages and disadvantages of PAK transplantation compared with
      simultaneous pancreas and kidney (SPK) transplantation and to review recent
      publications in an attempt to explain this phenomenon. RECENT FINDINGS: PAK
      transplantation has historically been associated with inferior pancreas allograft
      survival compared with SPK transplantation. Under modern immunosuppression
      protocols, pancreas allograft survival has improved substantially with rare
      immunological graft loss. According to several recent publications, it is
      controversial whether there is a survival advantage related to performing the
      pancreas transplant once the recipient has had a living donor renal transplant
      (LDRTx). SUMMARY: Considering that patient survival following SPK transplantation
      is significantly superior to that of recipients of LDRTx with type 1 diabetes
      alone and that LDRTx has demonstrated clear superiority in terms of renal
      allograft and patient survival over cadaveric renal transplantation, it would
      seem that PAK transplantation should be revisited as the option of choice for
      uremic recipients with diabetes.

PMID- 25563998
TI  - Pancreas transplant alone.
AB  - PURPOSE OF REVIEW: The present article aims to review the current state of
      diabetes, including its treatment options, and highlight current issues in
      pancreas transplantation. RECENT FINDINGS: Compared with other areas of
      transplantation, pancreas transplant/transplantation alone in the absence of
      kidney disease remains a relatively small field. As a consequence, reported new
      research articles are few in number, and often data regarding pancreas
      transplant/transplantation alone are mixed in with simultaneous kidney-pancreas
      and pancreas after kidney transplantation, which are covered separately. The
      prevalence of diabetes is reaching epidemic levels and continues to increase. New
      developments in diabetes care include the bionic pancreas and immunotherapy.
      Persistent efforts at gene and stem cell therapies are ongoing. Pancreas
      transplantation outcomes are improving, yet numbers are declining, even though
      pancreas transplantation still offers the most optimal glycemic control. SUMMARY:
      Pancreas transplantation has improving outcomes but stands in competition with
      other diabetes management options.

PMID- 25564001
TI  - Heavy metal concentrations in fishes from Juru River, estimation of the health
      risk.
AB  - This study examined the concentration of heavy metals in 13 fish species. The
      results indicated that shellfish species (clams) have the highest metal
      concentrations, followed by demersal and pelagic fishes. The mean concentration
      of metals in clams are Zn 88.74 +/- 11.98 ug/g, Cu 4.96 +/- 1.06 ug/g, Pb 1.22 +/
      0.19 ug/g, Cd 0.34 +/- 0.04 ug/g dry wt. basis, whereas the same measure in fish
      tissues was 58.04 +/- 18.51, 2.47 +/- 1.21, 0.58 +/- 0.27 and 0.17 +/- 0.08 ug/g
      dry wt. basis. The concentrations of heavy metals in clams and fish tissues were
      still lower than the maximum allowable concentrations as suggested by the
      Malaysian Food Act (1983) and are considered safe for local human consumption. 

PMID- 25564000
TI  - Lymphadenectomy should be performed up to the renal vein in patients with
      intermediate-high risk endometrial cancer.
AB  - We aimed to evaluate para-aortic metastases relative to the level of inferior
      mesenteric artery (IMA) and to discuss the clinico-pathological features of these
      patients. A total of 204 patients who underwent systematic pelvic and para-aortic
      lymphadenectomy up to the level of renal veins for endometrial cancer between
      January 2007 and August 2013 were included in this study. Of these 204 patients,
      44 (21.6 %) had lymph node involvement. From a total of 27 patients with
      paraaortic lymph node (PALN) metastasis, 11 had only supramesenteric and 4 had
      only inframesenteric nodal involvement, while 12 had both supramesenteric and
      inframesenteric metastases. Supramesenteric lymph node metastases were detected
      in 85.2 % of patients who have para-aortic metastases and in 11.3 % of all
      patients. Additionally, 5 patients had only supramesenteric lymphatic metastasis.
      The surgico-pathological characteristics of patients with isolated
      supramesenteric and inframesenteric metastasis were similar. However, the
      patients with lymphatic spread in both regions were found to have pelvic
      lymphatic metastasis and cervical invasion more commonly compared to patients
      with only supramesenteric or only inframesenteric metastasis. The site of
      metastatic lymph nodes wasn't associated with the likelihood and site of
      recurrence. Lymphadenectomy should be performed up to the level of renal vein in
      case of the presence of indication for lymphadenectomy in patients with
      endometrial cancer. Additionally, it is not possible to predict the patients with
      supramesenteric lymph node involvement by tumor grade, histological type and
      myometrial invasion.

PMID- 25564002
TI  - Biochemical and histological changes in fish, spotted scat (Scatophagus argus)
      exposed to diazinon.
AB  - Pesticide accumulates in aquatic ecosystems and exerts toxic effects on aquatic
      animals. In this study, stress parameters and tissue histopathology under acute
      diazinon exposure were investigated in fish, scat (Scatophagus argus). Spotted
      scat was exposed to different diazinon concentrations (0, 10, 20, 30 MUg L(-1))
      for 24, 48, 72, 96 h. Cortisol and glucose levels showed a significant increase
      after exposure to different diazinon concentration with increase in exposure
      time. The electrolytes (K(+), Cl(-), Ca(2+), Na(+)) and glucose were
      differentially affected during the exposure to diazinon. Gill and kidney tissues
      showed many histopathological changes in diazinon-exposed fish. These results
      suggest that the release of spotted scat (S. argus) into the diazinon
      contaminated regions may alter their physiology and jeopardize their survival. 

PMID- 25564003
TI  - Combinatorial biochemical and chemical analyses of polychlorinated dibenzo-p
      dioxins and dibenzofurans in agricultural soils from Chongming Island, Shanghai,
      China.
AB  - We compared polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F)
      concentrations [expressed as toxic equivalent quantities (TEQs)] in agricultural
      soil samples from Chongming Island (Shanghai, China) determined using two
      analytical approaches, an enzyme-linked immunoassay (EIA) method and a high
      resolution gas chromatography-high resolution mass spectrometry (HRGC/HRMS)
      method. The PCDD/F concentrations in all 31 soil samples were at background
      levels (7.30-16.7 pg EIA-TEQ/g from the EIA analysis and 0.526-1.99 pg WHO-TEQ/g
      from the HRGC/HRMS analysis). Although, the EIA method overestimated the PCDD/F
      concentrations compared with the concentrations determined using the HRGC/HRMS
      method. The absence of false-negatives showed by the EIA analysis verified that
      this method is useful for preliminary sample screening (prior to HRGC/HRMS
      analysis) and the preliminary characterization of potentially contaminated sites.

PMID- 25564004
TI  - Systematic review of rugby injuries in children and adolescents under 21 years.
AB  - A systematic review of rugby union and league injuries among players under the
      age of 21 years was carried out to calculate probabilities of match injury for a
      player over a season and a pooled estimate of match injury incidence where
      studies were sufficiently similar. The probability of a player being injured over
      a season ranged from 6% to 90% for rugby union and 68% to 96% for rugby league.
      The pooled injury incidence estimate for rugby union was 26.7/1000 player-hours
      for injuries irrespective of need for medical attention or time-loss and
      10.3/1000 player-hours for injuries requiring at least 7 days absence from games;
      equivalent to a 28.4% and 12.1% risk of being injured over a season. Study
      heterogeneity contributed to a wide variation in injury incidence. Public injury
      surveillance and prevention systems have been successful in reducing injury rates
      in other countries. No such system exists in the UK. 

PMID- 25564005
TI  - Ultrasound evaluation of focal neuropathies in athletes: a clinically-focused
      review.
AB  - Focal neuropathies represent a rare but clinically important and potentially
      challenging aetiology of pain in athletes. Diagnostic ultrasound is commonly used
      in the evaluation of nerve entrapments, and has several advantages over other
      imaging modalities, including high resolution, portability, lack of ionising
      radiation, low cost, point-of-care access, ease of contralateral comparison and
      capability of Doppler and dynamic imaging techniques. In this review, we discuss
      the use of ultrasound for the evaluation of injuries to the brachial plexus
      including 'stingers,' suprascapular nerve, ulnar nerve, radial nerve, common
      fibular nerve, tibial nerve and interdigital nerves of the foot at selected
      common sites of entrapment. 

PMID- 25564006
TI  - Using criteria-based interview models for assessing clinical expertise to select
      physiotherapists at major multisport games.
AB  - BACKGROUND: Benchmarking is an established means of identifying levels of
      specialist practice and competence-based interviews are a tool used to facilitate
      this. The London 2012 Olympic and Paralympic Games (LOCOG) provided an
      opportunity to introduce a pragmatic approach to assess expert behaviour in large
      numbers of volunteer physiotherapists. AIM: To test inter-tester repeatability of
      an assessment matrix used to score clinical expertise in a sporting context,
      followed by reporting on the findings for physiotherapy selection. METHODS: Four
      volunteers were videoed answering an identical sport-specific clinical scenario.
      Recordings were initially scored by two experienced assessors (gold standard).
      Subsequently, nine assessors scored the same videos then compared with the gold
      standard. 602 physiotherapists were assessed during volunteer interviews for
      LOCOG. Scores were compared to those based on self-reported clinical experience.
      Cross-tabulation was used to determine levels of agreement for the initial
      scoring matrix and the relationship between the two scoring systems was analysed.
      RESULTS: Levels of agreement ranged from 22% to 88%. A good correlation (r=0.754
      p>0.001) was found between self-reported clinical experience and scenario scores.
      Marginal data points in the correlational analysis indicated that only 52% of
      participants attained the same score across assessments. CONCLUSIONS: A tool to
      facilitate assessment for large scale selection could be used for Host Nation
      physiotherapist selection for Major Games. There is a need to train assessors in
      this environment, as well as provide detailed matrices, specific to each context
      being assessed, to ensure that observations can be made on domain-specific and
      general, non-technical aspects.

PMID- 25564009
TI  - Clinical significance of lesser occipital nerve preservation during micro
      vascular decompression for hemi-facial spasm.
AB  - BACKGROUND: Micro-vascular decompression (MVD) is a useful surgical technique in
      treating hemi-facial spasm (HFS). However, sensory disturbance and headache are
      the common postoperative complications. AIMS: This study seeked to estimate
      whether lesser occipital nerve (LON) preservation was conducive to reducing the
      incidence of adverse events. METHODS: We retrospectively compared the operation
      time and postoperative complications between 28 HFS patients who underwent MVD
      with LON preservation from January 2011 to December 2012 (LON preservation group)
      and 12 HFS patients who underwent MVD without preserving LON in 2010 (control
      group). RESULTS: Compared with the control group, patients in the LON
      preservation group showed increased operation time but reduced incidences of
      sensory disturbances around occipitalis (P = 0.017) and posterior auricular (P =
      0.002). However, there were no significant differences in other postoperative
      complications such as headache (P = 0.414), incision infection (P = 0.527) or
      cerebrospinal fluid leakage (P = 0.527). CONCLUSIONS: For HFS patients who
      attempted to receive MVD, LON preservation could reduce the incidence of sensory
      disturbance around the operative region, despite causing extend operation time.

PMID- 25564010
TI  - Re: cross-sectional audit on the relevance of Elevated National Early Warning
      Score in medical patients at a Model 2 hospital in Ireland.

PMID- 25564007
TI  - Diagnostic accuracy of neonatal kidney ultrasound in children having antenatal
      hydronephrosis without ureter and bladder abnormalities.
AB  - PURPOSE: To determine the diagnostic accuracy of anteroposterior renal pelvic
      diameter (APD) measurement and the society for fetal urology (SFU) grading in
      neonatal ultrasonography (USG) for detecting uropathy in newborns having
      antenatal isolated hydronephrosis (IH), characterized by hydronephrosis without
      ureter and bladder abnormalities, and to study time to resolution and factors
      predicting resolution of insignificant hydronephrosis. METHODS: Ninety-six
      healthy newborns (129 kidneys) with IH, who underwent USG at age 7-30 days and
      voiding cystourethrography (VCUG) in conjunction with diuretic renography (DR) if
      APD > 10 mm or SFU grade 3-4 in neonatal USG, and at least a 12-month follow-up
      were divided into significant and insignificant hydronephrosis using the combined
      data of sequential USG, VCUG, and DR as the reference standard. RESULTS: Areas
      under the receiver operating characteristic plots (95 % CI) were 0.86 (0.79-0.94)
      versus 0.81 (0.73-0.89); p = 0.08, and 87.6 versus 79.8 % of cases were correctly
      classified, for APD >= 16 mm versus SFU grade 4, respectively. Ureteropelvic
      junction obstruction (UPJO) was the most common uropathy diagnosed. Of 85 kidneys
      with insignificant hydronephrosis, 57 underwent spontaneous resolution. The
      resolution rates were 24, 40, and 68 % at age 6, 12, and 24 months, respectively.
      APD was the only independent factor predicting resolution with the hazard ratio
      of 0.83 (95 % CI 0.74-0.92; p = 0.001). CONCLUSIONS: In IH, neonatal USG was a
      useful diagnostic tool to detect uropathy, mainly UPJO. Further investigation
      should be recommended when APD >= 16 mm or SFU grade 4.

PMID- 25564012
TI  - Effects on life history variables and population dynamics following maternal
      metal exposure in the live-bearing fish Gambusia affinis.
AB  - This study investigated the effect of maternal copper and maternal cadmium
      exposure on life history variables and population dynamics in a live-bearing fish
      species. Gravid females were exposed to copper, cadmium, or background metal
      levels (control); maternal transfer of the metals was previously demonstrated
      using the exact same design. Each female's first brood, born after the exposure,
      was subdivided into two groups. One group was raised in the laboratory, to assess
      time-to and size-at sexual maturity, reproductive output and other life history
      variables. Offspring from the other group were used to start four mesocosm
      populations for each treatment. These populations were sampled monthly, for about
      18 months, to assess population dynamics. For the laboratory-reared fish,
      offspring of copper-exposed females reached sexual maturity at a smaller size
      than did offspring from the other treatments. Maternal copper exposure and
      maternal cadmium exposure both resulted in fewer broods and an increase in
      gestation time. No impacts were detected for brood size, inter-brood interval,
      time-to-sexual-maturity, or life span. In the greenhouse population study, no
      effect of maternal copper or cadmium exposure was evident for population
      parameters, other than that the relative abundance of juveniles and/or newborns
      was reduced in populations established with offspring of the exposed females.
      This study provided evidence that a short-term metal exposure of gravid females
      can negatively affect their offspring's life history variables and potentially
      influence population dynamics in a life-bearing fish species. 

PMID- 25564013
TI  - Sensitivity of animals to chemical compounds links to metabolic rate.
AB  - Ecotoxicological studies have shown considerable variation in species sensitivity
      for chemical compounds, but general patterns in sensitivity are still not known.
      A better understanding of this sensitivity is important in the context of
      environmental risk assessment but also in a more general ecological and
      evolutionary one. We investigated the metabolic rate or more precise the specific
      somatic maintenance (expressed in J cm(-3) d(-1), at a standardised body
      temperature of 20  degrees C) on the sensitivity of a species to chemical
      poisoning. The sensitivity of a species was expressed in terms of its threshold
      concentration for survival, the no effect concentrations (NEC, in umol/L).
      Somatic maintenance data were based on the 'add-my-pet' database hosted by the VU
      University of Amsterdam. NECs were derived from the US-EPA ECOTOX database. We
      focussed on four pesticides; two that need a metabolic activation, Chlorpyrifos
      and Malathion, and two without metabolic activation, carbofuran and carbaryl. All
      four pesticides showed a similar response: a strong negative correlation between
      the specific somatic maintenance and the NEC. We discuss possible explanations,
      deviations and ecological implications. 

PMID- 25564014
TI  - Evaluation of two-year Jewish genetic disease screening program in Atlanta:
      insight into community genetic screening approaches.
AB  - Improvements in genetic testing technologies have led to the development of
      expanded carrier screening panels for the Ashkenazi Jewish population; however,
      there are major inconsistencies in current screening practices. A 2-year pilot
      program was launched in Atlanta in 2010 to promote and facilitate screening for
      19 Jewish genetic diseases. We analyzed data from this program, including
      participant demographics and outreach efforts. This retrospective analysis is
      based on a de-identified dataset of 724 screenees. Data were obtained through
      medical chart review and questionnaires and included demographic information,
      screening results, response to outreach efforts, and follow-up behavior and
      preferences. We applied descriptive analysis, chi-square tests, and logistic
      regression to analyze the data and compare findings with published literature.
      The majority of participants indicated that they were not pregnant or did not
      have a partner who was pregnant were affiliated with Jewish organizations and
      reported 100 % AJ ancestry. Overall, carrier frequency was 1 in 3.9. Friends,
      rabbis, and family members were the most common influencers of the decision to
      receive screening. People who were older, had a history of pregnancy, and had
      been previously screened were more likely to educate others (all p < 0.05).
      Analysis of this 2-year program indicated that people who are ready to have
      children or expand their families are more likely to get screened and encourage
      others to be screened. The most effective outreach efforts targeted influencers
      who then encouraged screening in the target population. Educating influencers and
      increasing overall awareness were the most effective outreach strategies. 

PMID- 25564011
TI  - A new ensemble coevolution system for detecting HIV-1 protein coevolution.
AB  - BACKGROUND: A key challenge in the field of HIV-1 protein evolution is the
      identification of coevolving amino acids at the molecular level. In the past
      decades, many sequence-based methods have been designed to detect position
      specific coevolution within and between different proteins. However, an ensemble
      coevolution system that integrates different methods to improve the detection of
      HIV-1 protein coevolution has not been developed. RESULTS: We integrated 27
      sequence-based prediction methods published between 2004 and 2013 into an
      ensemble coevolution system. This system allowed combinations of different
      sequence-based methods for coevolution predictions. Using HIV-1 protein
      structures and experimental data, we evaluated the performance of individual and
      combined sequence-based methods in the prediction of HIV-1 intra- and inter
      protein coevolution. We showed that sequence-based methods clustered according to
      their methodology, and a combination of four methods outperformed any of the 27
      individual methods. This four-method combination estimated that HIV-1 intra
      protein coevolving positions were mainly located in functional domains and
      physically contacted with each other in the protein tertiary structures. In the
      analysis of HIV-1 inter-protein coevolving positions between Gag and protease,
      protease drug resistance positions near the active site mostly coevolved with Gag
      cleavage positions (V128, S373-T375, A431, F448-P453) and Gag C-terminal
      positions (S489-Q500) under selective pressure of protease inhibitors.
      CONCLUSIONS: This study presents a new ensemble coevolution system which detects
      position-specific coevolution using combinations of 27 different sequence-based
      methods. Our findings highlight key coevolving residues within HIV-1 structural
      proteins and between Gag and protease, shedding light on HIV-1 intra- and inter
      protein coevolution.

PMID- 25564015
TI  - Public health approach to birth defects: the Argentine experience.
AB  - Birth defects are a global problem, but their impact is particularly severe in
      low and middle income countries, where the conditions for prevention, treatment,
      and rehabilitation are more critical. The epidemiological transition in the
      infant mortality causes, and the concern of the community and the mass media
      about the teratogenic risk of environmental pollutants, has made health
      authorities aware of the importance of birth defects in Argentina. The objective
      of this paper is to outline those actions specifically taken in Argentina aimed
      at the prevention of birth defects at a national level. Firstly, we focus on
      birth defects in Argentina on a general basis, and then we present different laws
      and actions taken in terms of surveillance and public health programs, primary,
      secondary, and tertiary prevention. Finally, we present the Teratology
      Information Service "Fetal Health Line", and the genetic services organization
      and health professionals training by the National Center of Medical Genetics and
      the National Program of Genetics Network. In conclusion, in the country, several
      programs focus on different approaches to the problem, and the challenge is to
      coordinate the teamwork between them. Finally, we list tips to address birth
      defects from the public health perspective. 

PMID- 25564016
TI  - Markers of the hydration process during fluid volume modification in women with
      habitual high or low daily fluid intakes.
AB  - PURPOSE: Human daily total water intake (TWI) has a large inter-individual range.
      Recently, water supplementation has been suggested as a potential preventative
      and therapeutic modality. Thus, we aimed to measure hydration biomarkers in women
      with high (HIGH) versus low (LOW) daily TWI to determine baseline differences,
      and the efficacy of these markers during a systematic alteration in TWI. METHODS:
      This cohort study identified 14 HIGH [3.34 (0.56) L day(-1)] and 14 LOW [1.62
      (0.48) L day(-1)] from 120 women. Next, fluid intake was decreased in HIGH [2.00
      (0.21) L day(-1)] while LOW increased [3.50 (0.13) L day(-1)] across 4 days. Body
      mass, fluid intake, serum osmolality (S osmo), total plasma protein (TPP), 24 h
      urine osmolality, and 24 h urine volume, were measured on each day of modified
      TWI. Estimated plasma volume (E pv) was calculated using measured body mass and
      hematocrit values. RESULTS: At baseline, urinary markers and TPP differentiated
      HIGH from LOW [7.0 (0.3) versus 7.3 (0.3) mg dL(-1), respectively]. Upon TWI
      intervention, (1) body mass decreased in HIGH [-0.7 (1.1) kg, p = 0.010)] but did
      not increase in LOW [+0.0 (0.6) kg, p = 0.110], (2) E pv decreased 2.1 (2.4) %, p
      = 0.004, (3) urine osmolality increased in HIGH [397 (144)-605 (230) mOsm kg(-1),
      p < 0.001] and decreased in LOW [726 (248)-265 (97) mOsm kg(-1) p < 0.001], and
      (4) no changes of serum osmolality occurred in either HIGH or LOW (all p > 0.05).
      CONCLUSIONS: Urinary markers and TPP are sensitive measures to habitual high and
      low TWI and to changes in TWI. Both groups through urinary and some hematological
      responses following TWI manipulation achieved regulation of hemoconcentration.

PMID- 25564018
TI  - Synthesis of 1- and 4-substituted piperazin-2-ones via Jocic-type reactions with
      N-substituted diamines.
AB  - Enantiomerically-enriched trichloromethyl-containing alcohols, obtained by
      asymmetric reduction, can be transformed regioselectively into 1-substituted
      piperazinones by modified Jocic reactions with little or no loss of
      stereochemical integrity. This methodology can be easily used to synthesise
      important pharmaceutical compounds such as the fluorobenzyl intermediate of a
      known PGGTase-I inhibitor. 

PMID- 25564019
TI  - Warming-induced changes in predation, extinction and invasion in an ectotherm
      food web.
AB  - Climate change will alter the forces of predation and competition in temperate
      ectotherm food webs. This may increase local extinction rates, change the fate of
      invasions and impede species reintroductions into communities. Invasion success
      could be modulated by traits (e.g., defenses) and adaptations to climate. We
      studied how different temperatures affect the time until extinction of species,
      using bitrophic and tritrophic planktonic food webs to evaluate the relative
      importance of predatory overexploitation and competitive exclusion, at 15 and 25 
      degrees C. In addition, we tested how inclusion of a subtropical as opposed to a
      temperate strain in this model food web affects times until extinction. Further,
      we studied the invasion success of the temperate rotifer Brachionus calyciflorus
      into the planktonic food web at 15 and 25  degrees C on five consecutive
      introduction dates, during which the relative forces of predation and competition
      differed. A higher temperature dramatically shortened times until extinction of
      all herbivore species due to carnivorous overexploitation in tritrophic systems.
      Surprisingly, warming did not increase rates of competitive exclusion among the
      tested herbivore species in bitrophic communities. Including a subtropical
      herbivore strain reduced top-down control by the carnivore at high temperature.
      Invasion attempts of temperate B. calyciflorus into the food web always succeeded
      at 15  degrees C, but consistently failed at 25  degrees C due to voracious
      overexploitation by the carnivore. Pre-induction of defenses (spines) in B.
      calyciflorus before the invasion attempt did not change its invasion success at
      the high temperature. We conclude that high temperatures may promote local
      extinctions in temperate ectotherms and reduce their chances of successful
      recovery.

PMID- 25564017
TI  - Efficient inference of population size histories and locus-specific mutation
      rates from large-sample genomic variation data.
AB  - With the recent increase in study sample sizes in human genetics, there has been
      growing interest in inferring historical population demography from genomic
      variation data. Here, we present an efficient inference method that can scale up
      to very large samples, with tens or hundreds of thousands of individuals.
      Specifically, by utilizing analytic results on the expected frequency spectrum
      under the coalescent and by leveraging the technique of automatic
      differentiation, which allows us to compute gradients exactly, we develop a very
      efficient algorithm to infer piecewise-exponential models of the historical
      effective population size from the distribution of sample allele frequencies. Our
      method is orders of magnitude faster than previous demographic inference methods
      based on the frequency spectrum. In addition to inferring demography, our method
      can also accurately estimate locus-specific mutation rates. We perform extensive
      validation of our method on simulated data and show that it can accurately infer
      multiple recent epochs of rapid exponential growth, a signal that is difficult to
      pick up with small sample sizes. Lastly, we use our method to analyze data from
      recent sequencing studies, including a large-sample exome-sequencing data set of
      tens of thousands of individuals assayed at a few hundred genic regions. 

PMID- 25564021
TI  - A novel prescription for Alzheimer's disease: targeting hypercoagulable states.

PMID- 25564020
TI  - Identification of target antigens of antiendothelial cell antibodies against
      human brain microvascular endothelial cells in healthy subjects.
AB  - Antiendothelial cell antibodies (AECAs) have been detected in patients who have
      autoimmune and inflammatory diseases. Previous studies showed that AECAs against
      human umbilical vein endothelial cells were detected in healthy subjects. In the
      present study, we evaluated AECAs against human brain microvascular endothelial
      cells (HBMEC) in serum. We detected 250 antigen spots that reacted with AECAs in
      serum samples from 30 healthy subjects by 2-dimensional immunoblot using primary
      cultured HBMEC as the antigen source. There were 10 spots that corresponded to
      common target antigen spots and reacted with AECAs in serum samples from > 25% of
      the 30 healthy subjects. We identified 7 proteins that corresponded to 8 of the
      10 spots by mass spectrometry: 78-kDa glucose-regulated protein,
      dihydropyrimidinase-related protein 2, heterogeneous nuclear ribonucleoprotein L,
      vimentin, perilipin 3, alpha-enolase, and annexin A2. The results suggest that
      these 7 HBMEC proteins are major target antigens of natural AECAs. 

PMID- 25564023
TI  - Conserved and varied dinucleotide sequences in the genomes of three Aspergillus
      species.
AB  - Both guanine-cytosine content and nucleosome occupancy are higher in exons than
      in introns. In this study, the association between the frequencies of the
      dinucleotide sequences and the nucleosome occupancy of the exons and introns of
      the genes of Aspergillus fumigatus, Aspergillus nidulans, and Aspergillus oryzae
      was studied. The frequency of the dinucleotide sequences AA (TT), AT, and TA in
      the introns was more than that in the exons. In addition, the frequency of these
      sequences in the regions of the exons with low nucleosome occupancy was more than
      that in the regions with high nucleosome occupancy. On the other hand, the
      frequency of CC (GG), CG, and GC in the exons and in the regions of the exons
      with high nucleosome occupancy was higher than that in the introns and in the
      regions of low nucleosome occupancy, respectively. Interestingly, the frequency
      of the dinucleotide sequence AC (GT) was similar in the exons and introns of A.
      fumigatus. In A. nidulans, the frequency of AG (CT) and CA (TG) was similar in
      the regions of the exons with high and low nucleosome occupancy. In A. oryzae,
      the frequency of AG (CT) and GA (TC) was similar in the regions of the exons with
      high and low nucleosome occupancy. This study showed the conserved and varied
      dinucleotide sequences among the three species of Aspergillus. 

PMID- 25564022
TI  - Methods and compositions for amplification and detection of microRNAs (miRNAs)
      and noncoding RNAs (ncRNAs) using the signature sequence amplification method
      (SSAM).
AB  - The signature sequence amplification method (SSAM) described herein is an
      approach for amplifying noncoding RNA (ncRNA), microRNA (miRNA), and small
      polynucleotide sequences. A key point of the SSAM technology is the generation of
      signature sequences. The signature sequences include target sequences (miRNA,
      ncRNA, and/or any small polynucleotide sequence) flanked by two DNA fragments.
      Target sequences can be amplified through DNA synthesis, RNA synthesis, or the
      combination of DNA and RNA synthesis. The amplification of signature sequences
      provides an efficient and reproducible mechanism to determine the presence or
      absence of the target miRNAs/ncRNAs, to analyze the quantities of the miRNAs in
      biological samples, and for miRNA/ncRNA profiling. 

PMID- 25564024
TI  - Discovery of novel antibiotic resistance genes through metagenomics.
AB  - Antibiotic resistance (AR) represents a challenge for the treatment of infectious
      diseases. Traditionally, antibiotic resistance determinants have been retrieved
      from culturable bacteria which represent a minor fraction of the total microbial
      diversity found in natural environments such as soils. In this review, we
      summarize recent advances in the study of antibiotic resistance using two main
      culture-independent approaches: sequence-based metagenomics and functional
      metagenomics. 

PMID- 25564025
TI  - Analysis of simple sequence repeats in mammalian cell cycle genes.
AB  - Simple sequence repeats (SSRs), or microsatellites are hyper-mutable and can lead
      to disorders. Here we explore SSR distribution in cell cycle-associated genes
      [grouped into: checkpoint; regulation; replication, repair, and recombination
      (RRR); and transition] in humans and orthologues of eight mammals. Among the gene
      groups studied, transition genes have the highest SSR density. Trinucleotide
      repeats are not abundant and introns have higher repeat density than exons. Many
      repeats in human genes are conserved; however, CG motifs are conserved only in
      regulation genes. SSR variability in cell cycle genes represents a genetic
      Achilles' heel, yet SSRs are common in all groups of genes. This tolerance many
      be due to i) positions in introns where they do not disrupt gene function, ii)
      essential roles in regulation, iii) specific value of adaptability, and/or iv)
      lack of negative selection pressure. Present study may be useful for further
      exploration of their medical relevance and potential functionality. 

PMID- 25564026
TI  - Risk and protective effects of the complexin-2 gene and gene-environment
      interactions in schizophrenia.
AB  - Schizophrenia (SCZ) is a multifactorial chronic and disabling mental disease. The
      specific genetic variants contributing to disease complex phenotype are largely
      unknown. Growing amount of evidence suggested that aberrant synaptic connectivity
      contributes to SCZ pathogenesis. From this point of view, complexin-2, a
      presynaptic regulatory protein, represents here a special interest, since it has
      been recently shown that genetic variants of the CPLX2 gene may affect current
      cognitive performance in patients with SCZ. A specific objective of this study
      was to evaluate if tagging single nucleotide polymorphisms (rs3892909, rs1366116)
      of gene encoding complexin-2 protein (CPLX2) linked to SCZ and to examine their
      relationships with complexin-2 blood levels. DNA samples of 260 patients with SCZ
      and 260 sex- and age-matched healthy controls were genotyped for the selected
      polymorphisms by application of polymerase chain reaction with sequence-specific
      primers, and concentration of complexin-2 in the blood plasma was determined
      using the enzymelinked immunosorbent assay. All study subjects were unrelated
      Armenians. According to the obtained results, in the patients group both the
      frequency distribution and carriage rate of the CPLX2 rs1366116*T minor allele
      were higher than in controls. On the contrary, the frequency distribution and
      carriage rate of the CPLX2 rs3892909*T minor allele in control group were higher
      than in patients. This data suggested that the presence of the CPLX2 rs1366116*T
      allele increases susceptibility to SCZ, whereas the rs3892909*T allele of the
      CPLX2 decreases the risk of SCZ. Furthermore, we found that CPLX2 rs1366116*T
      heterozygosity is associated with earlier disease onset. No difference between
      complexin-2 plasma levels in patients and controls and no significant interaction
      between complexin-2 plasma levels and CPLX2 genotypes in both groups were
      observed. In summary, we concluded that the CPLX2 rs1366116*T variant represents
      a risk factor of SCZ, and that, at the same time, the CPLX2 rs3892909*T variant
      is protective against SCZ. 

PMID- 25564027
TI  - Effect of DNA microenvironment on photosensitized reaction of watersoluble
      cationic porphyrins.
AB  - Endogenous and exogenous photosensitizers induce DNA damage, leading to
      carcinogenesis. Further, DNA is an important target biomacromolecule of
      photodynamic therapy (PDT) for cancer. Since the solar-induced DNA damage and PDT
      reaction occur in a complex biological environment, the interaction between
      biomolecule and photosensitizer is important. In this study, we examined the
      effect of a DNA microenvironment on the photosensitized reaction by watersoluble
      porphyrin derivatives, tetrakis(N-methyl-p-pyridinio)porphyrin (H(2)TMPyP) and
      its zinc complex (ZnTMPyP). In the presence of a sufficient concentration of DNA,
      H(2)TMPyP mainly intercalates to calf thymus DNA, whereas ZnTMPyP binds into a
      DNA groove. An electrostatic interaction with DNA raises the redox potential of
      the binding porphyrins. This effect suppressed the photoinduced electron transfer
      from an electron donor to the DNA-binding porphyrins, whereas the electron
      transfer from the porphyrins to the electron acceptor was enhanced. In the case
      of hydrophobic electron acceptors, static complexes with porphyrins were formed,
      making rapid electron transfer possible. Since the interaction with DNA cleaved
      this complex, the electron transfer rate was decreased in the presence of DNA.
      The microenvironment of a DNA strand may assist or inhibit its oxidative damage
      by photoinduced electron transfer through an electrostatic interaction with
      binding photosensitizers and the steric effect.

PMID- 25564028
TI  - Recent patents on microbial proteases for the dairy industry.
AB  - This paper reviews the general characteristics of exo and endopeptidases of
      microbial origin currently used in the milk industry. It also includes recent
      patents developed either to potentiate the enzymatic activity or to improve the
      resulting milk derivatives. The main application of these proteases is in the
      cheese-making industry. Although this industry preferentially uses animal
      rennets, and in particular genetically engineered chymosins, it also utilizes
      milk coagulants of microbial origin. Enzymes derived from Rhizomucor miehei,
      Rhizomucor pusillus and Cryphonectria parasitica are currently used to replace
      the conventional milk-clotting enzymes. In addition, the dairy industry uses
      microbial endo and exoproteases for relatively new applications, such as
      debittering and flavor generation in cheese, accelerated cheese ripening,
      manufacture of protein hydrolysates with improved functional properties, and
      production of enzyme-modified cheeses. Lactic acid bacteria play an essential
      role in these processes, hence these bacteria and the proteases they produce are
      currently being investigated by the dairy industry and are the subject of many of
      their patent applications. 

PMID- 25564030
TI  - Oligodendroglial Development: New Roles for Chromatin Accessibility.
AB  - In the central nervous system, the generation of mature oligodendrocytes from
      their progenitors is a critical step in myelination, which is essential for
      normal nervous system function. Thus, understanding the regulatory mechanism
      underlying oligodendroglial development is of great importance, especially for
      the development of new therapeutic strategies that promote remyelination in
      demyelinating diseases, such as multiple sclerosis. Previous studies have focused
      on genetic patterns and revealed a network of cell signaling pathways and related
      transcription factors involved in oligodendroglial lineage development. Recently,
      epigenetic regulation, which refers to regulation of gene expression by adjusting
      the environment of the genes has been shown to play a profound role during
      oligodendroglial development. In this review, we summarize the recent data
      demonstrating the effects of chromatin modification and remodeling in regulating
      oligodendroglial development and discuss the use of high-throughput analysis and
      bio-informatics in future studies. 

PMID- 25564031
TI  - A shift of focus?

PMID- 25564033
TI  - IDS: Immediate Dentin Sealing (IDS) for tooth preparations.

PMID- 25564034
TI  - Applications of hydrophobins: current state and perspectives.
AB  - Hydrophobins are proteins exclusively produced by filamentous fungi. They self
      assemble at hydrophilic-hydrophobic interfaces into an amphipathic film. This
      protein film renders hydrophobic surfaces of gas bubbles, liquids, or solid
      materials wettable, while hydrophilic surfaces can be turned hydrophobic. These
      properties, among others, make hydrophobins of interest for medical and technical
      applications. For instance, hydrophobins can be used to disperse hydrophobic
      materials; to stabilize foam in food products; and to immobilize enzymes,
      peptides, antibodies, cells, and anorganic molecules on surfaces. At the same
      time, they may be used to prevent binding of molecules. Furthermore, hydrophobins
      have therapeutic value as immunomodulators and can been used to produce
      recombinant proteins. 

PMID- 25564035
TI  - Increased production of free fatty acids in Aspergillus oryzae by disruption of a
      predicted acyl-CoA synthetase gene.
AB  - Fatty acids are attractive molecules as source materials for the production of
      biodiesel fuel. Previously, we attained a 2.4-fold increase in fatty acid
      production by increasing the expression of fatty acid synthesis-related genes in
      Aspergillus oryzae. In this study, we achieved an additional increase in the
      production of fatty acids by disrupting a predicted acyl-CoA synthetase gene in
      A. oryzae. The A. oryzae genome is predicted to encode six acyl-CoA synthetase
      genes and disruption of AO090011000642, one of the six genes, resulted in a 9.2
      fold higher accumulation (corresponding to an increased production of 0.23 mmol/g
      dry cell weight) of intracellular fatty acid in comparison to the wild-type
      strain. Furthermore, by introducing a niaD marker from Aspergillus nidulans to
      the disruptant, as well as changing the concentration of nitrogen in the culture
      medium from 10 to 350 mM, fatty acid productivity reached 0.54 mmol/g dry cell
      weight. Analysis of the relative composition of the major intracellular free
      fatty acids caused by disruption of AO090011000642 in comparison to the wild-type
      strain showed an increase in stearic acid (7 to 26 %), decrease in linoleic acid
      (50 to 27 %), and no significant changes in palmitic or oleic acid (each around
      20-25 %).

PMID- 25564036
TI  - Gender Role Discrepancy Stress, High-Risk Sexual Behavior, and Sexually
      Transmitted Disease.
AB  - Nearly 20 million new sexually transmitted infections occur every year in the
      United States. Traditionally, men have demonstrated much greater risk for
      contraction of and mortality from STDs perhaps because they tend to engage in a
      number of risky sexual activities. Research on masculinity suggests that gender
      roles influence males' sexual health by encouraging risk-taking behavior,
      discouraging access to health services, and narrowly defining their roles as
      partners. However, despite the propensity of highly masculine men to engage in
      high-risk sexual behavior, there is reason to suspect that men at the other end
      of the continuum may still be driven to engage in similar high-risk behaviors as
      a consequence of gender socialization. Discrepancy stress is a form of gender
      role stress that occurs when men fail to live up to the ideal manhood derived
      from societal prescriptions (i.e., Gender Role Discrepancy). In the present
      study, we surveyed a national sample of 600 men via Amazon Mechanical Turk to
      assess perceived gender role discrepancy, experience of discrepancy stress, and
      the associations with risky sexual behavior and potential contraction of STDs.
      Results indicated that men who believe they are less masculine than the typical
      man (i.e., gender role discrepancy) and experience distress stemming from this
      discrepancy (i.e., discrepancy stress) engage in high-risk sexual behavior and
      are subsequently diagnosed with more STDs. Findings are discussed in relation to
      implications for primary prevention strategies. 

PMID- 25564037
TI  - A Comparative Analysis of a Community and General Sample of Lesbian, Gay, and
      Bisexual Individuals.
AB  - Samples recruited at lesbian, gay, and bisexual (LGB) venues have certain
      benefits, but a major drawback is that these samples are prone to bias as they
      only contain LGB participants who visit such venues. Empirical data with regard
      to the potential differences between LGB community samples and LGB general
      samples may shed some light on the generalizability of research findings from
      convenience samples recruited through LGB venues. The current study attempted to
      contribute to existing knowledge by examining differences in social demographics,
      sexual orientation, minority stress, and mental health between a convenience
      sample recruited at LGB venues ("community sample," N = 3,403) and an LGB sample
      recruited from a general research panel in the Netherlands ("panel sample," N =
      1,000). Various differences were found. In general, community participants were
      younger, reported a more exclusive same-sex sexual orientation, were more open
      about their sexual orientation, had lower levels of internalized homonegativity,
      and encountered more negative social reactions on their LGB status. They also
      reported higher levels of psychological distress and suicidality. The Nagelkerke
      R (2) of the analyses (which were adjusted for sociodemographic differences)
      ranged from .08 (suicide plans among men) to .27 (sexual attraction among women).
      However, while the estimates of sociodemographics, sexual orientation, minority
      stress, and mental well-being differed, the relationships between these
      constructs were comparable in both samples. Implications and suggestions for
      future studies are discussed.

PMID- 25564038
TI  - Lateralization for Processing Facial Emotions in Gay Men, Heterosexual Men, and
      Heterosexual Women.
AB  - This study tested whether male sexual orientation and gender nonconformity
      influenced functional cerebral lateralization for the processing of facial
      emotions. We also tested for the effects of sex of poser and emotion displayed on
      putative differences. Thirty heterosexual men, 30 heterosexual women, and 40 gay
      men completed measures of demographic variables, recalled childhood gender
      nonconformity (CGN), IQ, and the Chimeric Faces Test (CFT). The CFT depicts
      vertically split chimeric faces, formed with one half showing a neutral
      expression and the other half showing an emotional expression and performance is
      measured using a "laterality quotient" (LQ) score. We found that heterosexual men
      were significantly more right-lateralized when viewing female faces compared to
      heterosexual women and gay men, who did not differ significantly from each other.
      Heterosexual women and gay men were more left-lateralized for processing female
      faces. There were no significant group differences in lateralization for male
      faces. These results remained when controlling for age and IQ scores. There was
      no significant effect of CGN on LQ scores. These data suggest that gay men are
      feminized in some aspects of functional cerebral lateralization for facial
      emotion. The results were discussed in relation to the selectivity of functional
      lateralization and putative brain mechanisms underlying sexual attraction towards
      opposite-sex and same-sex targets. 

PMID- 25564039
TI  - Maximising the efficiency of clinical screening programmes: balancing predictive
      genetic testing with a right not to know.
AB  - We explored the dilemma between patients' right not to know their genetic status
      and the efficient use of health-care resources in the form of clinical cancer
      screening programmes. Currently, in the Netherlands, 50% risk carriers of
      heritable cancer syndromes who choose not to know their genetic status have
      access to the same screening programmes as proven mutation carriers. This implies
      an inefficient use of health-care resources, because half of this group will not
      carry the familial mutation. At the moment, only a small number of patients are
      involved; however, the expanding possibilities for genetic risk profiling means
      this issue must be addressed because of potentially adverse societal and
      financial impact. The trade-off between patients' right not to know their genetic
      status and efficient use of health-care resources was discussed in six focus
      groups with health-care professionals and patients from three Dutch university
      hospitals. Professionals prefer patients to undergo a predictive DNA test as a
      prerequisite for entering cancer screening programmes. Professionals prioritise
      treating sick patients or proven mutation carriers over screening untested
      individuals. Participation in cancer screening programmes without prior DNA
      testing is, however, supported by most professionals, as testing is usually
      delayed and relatively few patients are involved at present. Reducing the number
      of 50% risk carriers undergoing screening is expected to be achieved by: offering
      more psychosocial support, explaining the iatrogenic risks of cancer screening,
      increasing out-of-pocket costs, and offering a less stringent screening programme
      for 50% risk carriers. 

PMID- 25564040
TI  - Mitochondrial genome diversity at the Bering Strait area highlights prehistoric
      human migrations from Siberia to northern North America.
AB  - The patterns of prehistoric migrations across the Bering Land Bridge are far from
      being completely understood: there still exists a significant gap in our
      knowledge of the population history of former Beringia. Here, through
      comprehensive survey of mitochondrial DNA genomes retained in 'relic'
      populations, the Maritime Chukchi, Siberian Eskimos, and Commander Aleuts, we
      explore genetic contribution of prehistoric Siberians/Asians to northwestern
      Native Americans. Overall, 201 complete mitochondrial sequences (52 new and 149
      published) were selected in the reconstruction of trees encompassing mtDNA
      lineages that are restricted to Coastal Chukotka and Alaska, the Canadian Arctic,
      Greenland, and the Aleutian chain. Phylogeography of the resulting mtDNA genomes
      (mitogenomes) considerably extends the range and intrinsic diversity of
      haplogroups (eg, A2a, A2b, D2a, and D4b1a2a1) that emerged and diversified in
      postglacial central Beringia, defining independent origins of Neo-Eskimos versus
      Paleo-Eskimos, Aleuts, and Tlingit (Na-Dene). Specifically, Neo-Eskimos,
      ancestral to modern Inuit, not only appear to be of the High Arctic origin but
      also to harbor Altai/Sayan-related ancestry. The occurrence of the haplogroup
      D2a1b haplotypes in Chukotka (Sireniki) introduces the possibility that the
      traces of Paleo-Eskimos have not been fully erased by spread of the Neo-Eskimos
      or their descendants. Our findings are consistent with the recurrent gene flow
      model of multiple streams of expansions to northern North America from
      northeastern Eurasia in late Pleistocene-early Holocene. 

PMID- 25564042
TI  - Schneiderian-Type Papilloma of the Middle Ear: A Review of the Literature.
AB  - Schneiderian-type papilloma of the middle ear is a rare finding. We present a 46
      year-old Aboriginal man with a large tympanic membrane perforation and a
      Schneiderian-type papilloma filling the middle ear. The aim of this study is to
      familiarize clinicians with this uncommon disease through discussion of its
      clinical presentation, diagnostic considerations and management. A search of
      English-language peer-reviewed literature was undertaken using the key words
      "Schneiderian-type papilloma," "inverted papilloma," and "middle ear." A total of
      29 cases (including the present case) of Schneiderian-type papilloma involving
      the middle ear were reviewed. Common presenting symptoms include hearing loss,
      otalgia, and otorrhea. Middle ear disease is associated with higher rates of
      recurrence and malignant transformation than its sinonasal counterpart. Radical
      surgical resection is the only curative treatment. Schneiderian-type papilloma is
      a benign, but locally aggressive, epithelial neoplasm most commonly arising in
      the sinonasal tract. Whilst involvement of the middle ear is extremely rare,
      knowledge of this condition is important due to its propensity to recur and the
      high rate of malignant transformation. 

PMID- 25564041
TI  - Primary coenzyme Q10 deficiency presenting as fatal neonatal multiorgan failure.
AB  - Coenzyme Q10 deficiency is a clinically and genetically heterogeneous disorder,
      with manifestations that may range from fatal neonatal multisystem failure, to
      adult-onset encephalopathy. We report a patient who presented at birth with
      severe lactic acidosis, proteinuria, dicarboxylic aciduria, and hepatic
      insufficiency. She also had dilation of left ventricle on echocardiography. Her
      neurological condition rapidly worsened and despite aggressive care she died at
      23 h of life. Muscle histology displayed lipid accumulation. Electron microscopy
      showed markedly swollen mitochondria with fragmented cristae. Respiratory-chain
      enzymatic assays showed a reduction of combined activities of complex I+III and
      II+III with normal activities of isolated complexes. The defect was confirmed in
      fibroblasts, where it could be rescued by supplementing the culture medium with
      10 MUM coenzyme Q10. Coenzyme Q10 levels were reduced (28% of controls) in these
      cells. We performed exome sequencing and focused the analysis on genes involved
      in coenzyme Q10 biosynthesis. The patient harbored a homozygous c.545T>G,
      p.(Met182Arg) alteration in COQ2, which was validated by functional
      complementation in yeast. In this case the biochemical and morphological features
      were essential to direct the genetic diagnosis. The parents had another pregnancy
      after the biochemical diagnosis was established, but before the identification of
      the genetic defect. Because of the potentially high recurrence risk, and given
      the importance of early CoQ10 supplementation, we decided to treat with CoQ10 the
      newborn child pending the results of the biochemical assays. Clinicians should
      consider a similar management in siblings of patients with CoQ10 deficiency
      without a genetic diagnosis.

PMID- 25564043
TI  - Probing dynamics and pinning of single vortices in superconductors at nanometer
      scales.
AB  - The dynamics of quantized magnetic vortices and their pinning by materials
      defects determine electromagnetic properties of superconductors, particularly
      their ability to carry non-dissipative currents. Despite recent advances in the
      understanding of the complex physics of vortex matter, the behavior of vortices
      driven by current through a multi-scale potential of the actual materials defects
      is still not well understood, mostly due to the scarcity of appropriate
      experimental tools capable of tracing vortex trajectories on nanometer scales.
      Using a novel scanning superconducting quantum interference microscope we report
      here an investigation of controlled dynamics of vortices in lead films with sub
      Angstrom spatial resolution and unprecedented sensitivity. We measured, for the
      first time, the fundamental dependence of the elementary pinning force of
      multiple defects on the vortex displacement, revealing a far more complex
      behavior than has previously been recognized, including striking spring softening
      and broken-spring depinning, as well as spontaneous hysteretic switching between
      cellular vortex trajectories. Our results indicate the importance of thermal
      fluctuations even at 4.2 K and of the vital role of ripples in the pinning
      potential, giving new insights into the mechanisms of magnetic relaxation and
      electromagnetic response of superconductors. 

PMID- 25564044
TI  - Adsorption and adhesion of common serum proteins to nanotextured gallium nitride.
AB  - As the broader effort towards device and material miniaturization progresses in
      all fields, it becomes increasingly important to understand the implications of
      working with functional structures that approach the size scale of molecules,
      particularly when considering biological systems. It is well known that thin
      films and nanostructures feature different optical, electrical, and mechanical
      properties from their bulk composites; however, interactions taking place at the
      interface between nanomaterials and their surroundings are less understood. Here,
      we explore interactions between common serum proteins - serum albumin,
      fibrinogen, and immunoglobulin G - and a nanotextured gallium nitride surface.
      Atomic force microscopy with a carboxyl-terminated colloid tip is used to probe
      the 'activity' of proteins adsorbed onto the surface, including both the
      accessibility of the terminal amine to the tip as well as the potential for
      protein extension. By evaluating the frequency of tip-protein interactions, we
      can establish differences in protein behaviour on the basis of both the surface
      roughness as well as morphology, providing an assessment of the role of surface
      texture in dictating protein-surface interactions. Unidirectional surface
      features - either the half-unit cell steppes of as-grown GaN or those produced by
      mechanical polishing - appear to promote protein accessibility, with a higher
      frequency of protein extension events taking place on these surfaces when
      compared with less ordered surface features. Development of a full understanding
      of the factors influencing surface-biomolecule interactions can pave the way for
      specific surface modification to tailor the bio-material interface, offering a
      new path for device optimization. 

PMID- 25564045
TI  - Innovations in using virtual reality to study how children cross streets in
      traffic: evidence for evasive action skills.
AB  - PURPOSE: Children in middle childhood are at an increased risk for injury in
      pedestrian environments. This study examined whether they are capable of showing
      evasive action (ie, adjusting crossing speed) to avoid injury when crossing
      streets. METHODS: The study used a fully immersive virtual reality (VR) system
      interfaced with a three-dimensional movement measurement system so that the
      actual crossing behaviour of 7-10-year-old children under different traffic
      conditions could be precisely measured. Relating outcomes to that which would
      have been obtained based on using the approach of estimating walking speed and
      assuming a constant speed provided insights into the realised benefits of the
      current movement monitoring VR system. RESULTS: Controlling for age and sex,
      children showed evasive action, crossing more quickly as traffic conditions
      became more risky. Using an average and assuming a constant walking speed
      underestimated actual walking speed, failing to capture evasive action and
      leading to overestimation of children being hit compared with the actual
      incidence of hits. CONCLUSIONS: VR technology is a valuable tool for assessing
      child pedestrian behaviour. However, systems need to allow the child to cross the
      street so their level of pedestrian skill is appropriately measured. The current
      findings provide the first evidence that children are capable of implementing
      evasive action in reaction to risky traffic conditions.

PMID- 25564046
TI  - A stable zinc-4-carboxypyrazole framework with high uptake and selectivity of
      light hydrocarbons.
AB  - A special organic ligand, 4-carboxypyrazole (4-cpz), is chosen to synthesize a
      highly stable metal-organic framework (MOF) for selective sorption of light
      hydrocarbons. The new MOF, (H(3)O)[Zn(3)(OH)(4-cpz)3].2(DEF).H(2)O (FIR-51, DEF =
      N,N-diethylformamide), was synthesized solvothermally and shows unusual chemical
      stability. This compound exhibits high storage capacity for light hydrocarbons
      and high selectivity for C3 and C2 over methane at 273 and 294 K.

PMID- 25564048
TI  - Room-temperature single-photon level memory for polarization states.
AB  - An optical quantum memory is a stationary device that is capable of storing and
      recreating photonic qubits with a higher fidelity than any classical device. Thus
      far, these two requirements have been fulfilled for polarization qubits in
      systems based on cold atoms and cryogenically cooled crystals. Here, we report a
      room-temperature memory capable of storing arbitrary polarization qubits with a
      signal-to-background ratio higher than 1 and an average fidelity surpassing the
      classical benchmark for weak laser pulses containing 1.6 photons on average,
      without taking into account non-unitary operation. Our results demonstrate that a
      common vapor cell can reach the low background noise levels necessary for
      polarization qubit storage using single-photon level light, and propels atomic
      vapor systems towards a level of functionality akin to other quantum information
      processing architectures. 

PMID- 25564049
TI  - Divergent pathways to furosesquiterpenes: first total syntheses of (+)-zedoarol
      and (Rac)-gweicurculactone.
AB  - A non-natural hydroxy-elemane was found amenable to divergent transformations,
      producing either polyunsaturated guaianes under basic, oxygen-free conditions, or
      oxidized furogermacranes when anionic oxy-Cope reaction quenched by an oxidant is
      employed. Based on these findings, the first total syntheses of zedoarol and
      gweicurculactone are reported. 

PMID- 25564050
TI  - Density functional theory study on boron- and phosphorus-doped hydrogen
      passivated silicene.
AB  - When silicene is passivated by hydrogen, a bandgap occurs so that it becomes a
      semiconductor. Analogous to all the other semiconductors, doping is highly
      desired to realize the potential of hydrogen-passivated silicene (H-silicene). In
      the framework of density functional theory (DFT), we have studied the doping of H
      silicene with boron (B) and phosphorus (P). The concentration of B or P ranges
      from 1.4% to 12.5%. It is found that the doping of B or P enables the indirect
      bandgap H-silicene to be a semiconductor with a direct bandgap. With the increase
      of the concentration of B or P, both the valence band and the conduction band
      shift to lower energies, while the bandgap decreases. Both B- and P-doping lead
      to the decrease of the effective mass of holes and electrons in H-silicene. For
      both B- and P-doped H-silicene a subband absorption peak may appear, which
      blueshifts with the increase of the dopant concentration. 

PMID- 25564047
TI  - Impact of fish oils on the outcomes of a mouse model of acute Pseudomonas
      aeruginosa pulmonary infection.
AB  - Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that causes
      pneumonia in immunocompromised humans and severe pulmonary damage in patients
      with cystic fibrosis. Imbalanced fatty acid incorporation in membranes, including
      increased arachidonic acid and decreased DHA concentrations, is known to play a
      critical role in chronic inflammation associated with bacterial infection. Other
      lipids, such as EPA and alkylglycerols, are also known to play a role in
      inflammation, particularly by stimulating the immune system, decreasing
      inflammation and inhibiting bacterial growth. In this context, the goal of the
      present study was to assess the effect of dietary DHA/EPA, in a 2:1 ratio, and
      alkylglycerols, as natural compounds extracted from oils of rays and chimeras,
      respectively, on the inflammatory reaction induced by P. aeruginosa pulmonary
      infection in mice. To this end, mice were fed with a control diet or isolipidic,
      isoenergetic diets prepared with oils enriched in DHA/EPA (2:1) or alkylglycerols
      for 5 weeks before the induction of acute P. aeruginosa lung infection by
      endotracheal instillation. In our model, DHA/EPA (2:1) significantly improved the
      survival of mice after infection, which was associated with the acceleration of
      bacterial clearance and the resolution of inflammation leading to the improvement
      of pulmonary injuries. By contrast, alkylglycerols did not affect the outcomes of
      P. aeruginosa infection. Our findings suggest that supplementation with ray oil
      enriched in DHA/EPA (2:1) can be considered as a preventive treatment for
      patients at risk for P. aeruginosa infection. 

PMID- 25564051
TI  - [Research progress in nonsurgical treatment response evaluation criteria for
      esophageal cancer].

PMID- 25564052
TI  - [Enhanced growth inhibition by combined two pathway inhibitors on K-ras mutated
      non-small cell lung cancer cells].
AB  - OBJECTIVE: To evaluate the effect of combined targeting of MEK and PI3K signaling
      pathways on K-ras mutated non-small cell lung cancer cell line A549 cells and the
      relevant mechanisms. METHODS: A549 cells were treated with different
      concentrations of two inhibitors. Growth inhibition was determined by MTT assay.
      According to the results of MTT test, the cells were divided into four groups:
      the control group, PI3K inhibitor group (GDC-0941,0.5 and 5.0 umol/L),
      combination group I (0.5 umol/L AZD6244+0.5 umol/L GDC-0941) and combination
      group II (5.0 umol/L AZD6244+5.0 umol/L GDC-0941). The cell cycle and apoptosis
      were analyzed by flow cytometry. The expression of proteins related to apoptosis
      was tested with Western blot. RESULTS: Both GDC-0941 and AZD6244 inhibited the
      cell proliferation. The combination group II led to a stronger growth inhibition.
      The combination group I showed an antagonistic effect and combination group II
      showed an additive or synergistic effect. Compared with the control group, the
      combination group I led to reduced apoptotic rate [(20.70 +/- 0.99)% vs. (18.65
      +/- 0.92 )%, P > 0.05]; Combination group II exhibited enhanced apoptotic rate
      [(37.85 +/- 3.18)% vs. (52.27 +/- 4.36)%, P < 0.01]. In addition, in the
      combination group II, more A549 cells were arrested in G0/G1 phase and decreased
      S phase (P < 0.01), due to the reduced expressions of CyclinD1 and Cyclin B1, the
      increased cleaved PARP and the diminished ratio of Bcl-2/Bax. CONCLUSIONS: For
      single K-ras mutated NSCLC cell line A549 cells, combination of RAS/MEK/ERK and
      PI3K/AKT/mTOR inhibition showed synergistic effects depending on the drug doses.
      Double pathways targeted therapy may be beneficial for these patients.

PMID- 25564053
TI  - [Cetuximab in combination with icotinib overcomes the acquired resistance caused
      by EGFR T790M mutation in non-small cell lung cancer].
AB  - OBJECTIVE: The aim of this study was to investigate the effects of combination of
      icotinib and cetuximab on the acquired drug resistance caused by T790M mutation
      of EGFR in NSCLC, and provide experimental evidence for rational treatment of
      NSCLC. METHODS: The effects of these two agents on cell proliferation, apoptosis,
      and EGFR-dependent signaling were evaluated using 3-(4, 5-dimethylthiazol-2-yl)-
      5-diphenyltetrazolium bromide (MTT) assay, annexin V staining, and Western
      blotting. The expression of molecular markers of tumor proliferation PCNA and Ki
      67 protein was further examined by immunohistochemistry, and the expression of
      EGFR-signaling-related proteins in tissue sections taken from H1975 tumor
      xenografts was assessed by Western blot assay. Sensitivity to EGFR inhibitors was
      detected in human H1975 tumor xenograft in nude mice. RESULTS: The in vitro
      experiment showed that the proliferative ability of H1975 cells was inhibited in
      a dose-dependent manner, along with the increasing doses of cetuximab and
      icotinib, and the combination of cetuximab with icotinib resulted in a more
      pronounced growth inhibition of the H1975 cells. The apoptosis rate of H1975
      cells after treatment with 0.5 umol/L icotinib and 1 ug/ml cetuximab was (22.03
      +/- 2.41)% and that after treatment with 5 umol/L icotinib and 10 ug/ml cetuximab
      was (42.75 +/- 2.49)%, both were significantly higher than that after treatment
      with the same dose of icotinib or cetuximab alone (P < 0.05). The nude mouse
      experiment showed that the transplanted tumor was growing to (614.5 +/- 10.8)
      mm(3) in the blank control group and to (611.2 +/- 8.7) mm(3) at 28 days after
      icotinib treatment, but (30.8 +/- 2.0) mm(3) in the cetuximab treatment group and
      0 mm(3) in the cetuximab combined with icotinib group. There was a significantly
      decreased expression of Ki-67 and PCNA proteins and down-regulation of
      phosphorylation of EGFR signaling-related proteins in the cetuximab combined with
      icotinib group. CONCLUSIONS: The combination of icotinib with cetuximab can exert
      synergistic inhibitory effect on the acquired drug resistance caused by T790M
      mutation of EGFR in NSCLC H1975 cells, interrupts the EGFR-downstream signaling
      pathway, and enhances the anticancer activity of chemotherapeutic drugs. Our
      results provide further experimental evidence for the clinical studies of
      combination of icotinib with cetuximab in the treatment of NSCLC patients
      associated with secondary drug resistance caused by T790M mutation of EGFR.

PMID- 25564054
TI  - [Mechanisms regulating p21 gene expression by retinoic acid-induced gene G
      protein].
AB  - OBJECTIVE: To investigate the mechanisms by which retinoic acid-induced gene G
      (RIG-G) protein regulates p21 gene expression. METHODS: Western blot was used to
      detect the effects of RIG-G protein overexpression on p21 protein expression
      level in leukemia cell line NB4 cells and the phosphorylation of both c-Jun and
      JNK in U937 cells. The c-Jun expression plasmid and p21 gene promoter-containing
      reporter plasmid were co-transfected into 293T cells, to explore the regulatory
      effect of c-Jun protein on p21 gene expression by luciferase reporter assay.
      RESULTS: Western blot showed that the overexpression of RIG-G protein
      significantly upregulated p21 protein level in the NB4 cells, and the level of
      p21 protein largely increased along with the induction of endogenous RIG-G
      protein during the differentiation of NB4 cells treated by all-trans retinoic
      acid (ATRA). Moreover, the phosphorylation of both c-Jun and JNK decreased in RIG
      G-overexpressing U937 cells while total c-Jun and JNK proteins remained
      unchanged. After using the JNK inhibitor SP600125 to block JNK phosphorylation,
      the level of c-Jun phosphorylation was still dramatically reduced in the RIG-G
      overexpressing U937T-RIG-G cells, compared with the control U937T-pTRE cells.
      These results indicated that the inhibitory effect of Rig-G protein on c-Jun
      phosphorylation could not only be through the JNK pathway, but also via some JNK
      independent pathways. Luciferase reporter assay showed that when 0.1, 0.5, 1.0
      and 2.0 ug c-Jun-expressing plasmids were respectively transfected into 293T
      cells, compared with the empty vector-transfected group, the relative luciferase
      activities were (83.0 +/- 1.7)%, (73.7 +/- 0.7)%, (68.9 +/- 0.9)% and (64.1 +/-
      0.9)%, indicating that the transcriptional activity of p21 gene could be
      inhibited by c-Jun protein. CONCLUSIONS: RIG-G protein may suppress the
      phosphorylation of c-Jun protein through different signal pathways, thereby
      increasing the expression of p21 gene, arresting the cell cycle and inhibiting
      the cell growth in U937 cells.

PMID- 25564055
TI  - [Correlation between clinicopathological features and CA19-9/CEA in patients with
      extrahepatic cholangiocarcinoma].
AB  - OBJECTIVE: To study the correlation between clinicopathological features and
      serum carbohydrate antigen 19-9 (CA19-9)/carcinoembryonic antigen (CEA) in
      patients with extrahepatic cholangiocarcinoma (ECC). METHODS: The
      clinicopathological data of 126 cases of extrahepatic cholangiocarcinoma treated
      in our department from Jan. 1999 to Dec. 2012 were collected and analyzed in this
      study. The correlation between clinicopathological features and sensitivity of
      CA19-9/CEA was analyzed by chi-square test. The correlation of
      clinicopathological features and value of serum CA19-9/CEA was analyzed by t test
      and F test. RESULTS: The average value of CA19-9 before surgery in the 126
      patients was 595.3 U/ml. The values of CA19-9 in 91 patients were abnormal and
      the sensitivity of CA19-9 was 72.2%. The average value of CEA before surgery was
      12.6 U/ml. The value of CEA in 26 patients were abnormal and the sensitivity of
      CEA was 20.6%. The values of combined detection of serum CA19-9 and CEA before
      surgery were abnormal in a total of 97 cases with a sensitivity of 77.0%. There
      was no significant correlation between clinicopathological features and
      sensitivity of CA19-9 (P > 0.05). The location of tumor was significantly
      correlated to the diagnostic sensitivity of CEA. The sensitivity of CEA to distal
      ECC was only 15.4%. The value of CA19-9 was relatively high in patients >60-year
      old or with neural invasion, while CEA was higher when tumor was located in the
      middle of bile duct (P < 0.05). There was no significant difference of serum CA19
      9 before and after jaundice reduction (P > 0.05). CONCLUSIONS: The diagnostic
      sensitivity of CA19-9 is not affected by gender, age, blood type, tumor location,
      degree of differentiation, tumor size, T stage, vascular tumor thrombus, lymph
      node metastasis, perineural invasion, and preoperative jaundice. However, the
      diagnostic sensitivity of CEA is affected by tumor location. The value of CA19-9
      is correlated with tumor invasion and is relatively high in patients above 60
      years old.

PMID- 25564056
TI  - [Ki-67 expression in stage III cervical squamous cell carcinoma and its
      correlation with sensitivity to chemoradiotherapy].
AB  - OBJECTIVE: To investigate the expression of proliferating cell nuclear antigen
      (Ki-67) in stage III cervical squamous cell carcinoma (SCC) and its correlation
      with the effect of chemotherapy on sensitivity to radiotherapy. METHODS: In 50
      patients with stage III cervical squamous cell carcinoma (SCC), 25 patients were
      treated with radiotherapy and 25 patients were treated with chemoradiotherapy.
      The expression of Ki-67 in the biopsy specimens of cervical SCC was detected by
      immunohistochemistry at diagnosis and after 10 Gy radiotherapy. The correlation
      of Ki-67 positive cells percentage and chemotherapy with sensitivity to
      radiotherapy was analyzed. RESULTS: In 25 patients with more than 48% Ki-67
      positive cells at diagnosis, the rate of complete response (CR) was 72.0%
      (18/25). In 25 patients with less than 48% Ki-67 positive cells at diagnosis, the
      CR rate was 40.0% (10/25), with a significant difference between them (P =
      0.023). In 26 patients with more than 31% decrease of Ki-67 positive cells after
      10 Gy radiotherapy, the CR rate was 84.6% (22/26). In 24 patients with less than
      31% decrease of Ki-67 positive cells after 10 Gy radiotherapy, the CR rate was
      25.0% (6/24), showing a significant difference between the two groups (P <
      0.001). In the cases of Ki-67<48%, decrease of Ki-67 positive cells of
      chemoradiotherapy group after 10 Gy radiotherapy was significantly higher than
      that of the radiotherapy group (P = 0.023). In the cases of Ki-67 >= 48%, no
      difference in the decease of Ki-67 positive cells between the chemoradiotherapy
      and radiotherapy groups was found (P = 0.173). For the radiotherapy-sensitive
      patients with CR recently, the 2-year progression free survival (PFS) rate and
      overall survival (OS) rate were 85.7% and 92.9%, respectively, both were
      significantly higher than those of radiotherapy-insensitive patients (18.2% and
      40.9%, P < 0.05 for both). CONCLUSIONS: In stage III cervical SCC, the expression
      of Ki-67 before and after treatment with 10 Gy radiotherapy may be used as a
      biomarker to predict tumor response to radiation, and guide the choice of
      therapeutic strategies. Yet, the effect of chemotherapy as a radiosensitizer is
      unconspicuous.

PMID- 25564057
TI  - [Prognostic significance of Ki-67 expression before and after neoadjuvant
      chemotherapy in different biological breast cancer phenotypes].
AB  - OBJECTIVE: This study was conducted to analyze the Ki-67 expression before and
      after neoadjuvant chemotherapy and clinicopathological characteristics of
      different biological breast cancer phenotypes. The significance and prognostic
      predictive value of the changes of Ki-67 expression in different biological
      breast cancer phenotypes were analyzed. METHODS: A regression analysis was
      performed on 178 patients with invasive breast carcinoma who accepted neoadjuvant
      chemotherapy at Tianjin Medical University Cancer Institute and Hospital from
      August 2007 to August 2008. These patients were subtyped by hormone receptor
      status and HER-2 status. The Ki-67 index (percentage of Ki-67-positive cancer
      cell nuclei) was determined by immunohistochemistry. The prognostic value of Ki
      67 index for disease-free survival (DFS) in different biological breast cancer
      phenotypes was analyzed using Kaplan-Meier survival and multivariable Cox
      regression. RESULTS: The overall pathologic CR (pCR) rate, defined as no invasive
      residuals in the breast and axilla, was 15.2%. The highest pCR rate of 25.0% was
      observed in the TNBC patients, which was 14.3%, 10.3% and 18.2% in the luminal A,
      luminal B and HER2 overexpressing patients, respectively (P = 0.040). The changes
      of Ki-67 expression in pre-NAC and post-NAC patients showed a prognostic
      significance in luminal A and TNBC (P = 0.019 and P = 0.022, respectively) cases.
      Clinical stage, the efficacy of NAC, and changes of Ki-67 expression between pre-
      and post-NAC were independent prognostic factors in TNBC patients who did not
      achieve pCR. CONCLUSIONS: The Ki-67 expression after neoadjuvant chemotherapy is
      an independent prognostic factor affecting the disease-free survival (DFS) in
      TNBC patients who have not achieved pCR.

PMID- 25564058
TI  - [Comparison of the whole breast target volume delineated according to surface
      marks, palpation and glandular tissue on CT images after breast-conserving
      surgery].
AB  - OBJECTIVE: To compare the methods of delineating the whole breast target volume
      based on surface marks, palpation and glandular tissue on CT images, and to
      explore the contouring criteria after breast-conserving surgery. METHODS: In 15
      patients with breast cancer after breast-conserving surgery, the whole breast
      target was delineated in 3D CT simulation images each by three different methods.
      The target volume delineated according to anatomical marks were named CTVan,
      according to breast palpation named CTVpa, and according to glandular mammary
      tissue showing by CT images named CTVgl. The volumes of CTVan, CTVpa and CTVgl,
      and the degree of inclusion (DI) and conformal index (CI) between the targets
      were measured. RESULTS: The mean volumes of CTVan, CTVpa and CTVgl were (792.23
      +/- 282.25) cm(3), (618.33 +/- 295.90) cm(3) and (196.83 +/- 117.62) cm(3),
      respectively. The differences among the three methods were statistically
      significant (P < 0.001). The difference between CTVan and CTVpa had no
      statistical significance (P = 0.08), and both the differences between CTVan and
      CTVgl, and between CTVpa and CTVgl had statistical significance (both P < 0.001).
      The CI between CTVan and CTVpa (0.644 +/- 0.122) was significantly larger than
      the CI between CTVan and CTVgl (0.264 +/- 0.108), and the CI between CTVpa and
      CTVgl (0.328 +/- 0.115)(P < 0.001). The DI of CTVan to CTVpa was 0.709 +/-
      0.144,DI of CTVgl to CTVan was 0.994 +/- 0.005 and DI of CTVgl to CTVpa was 0.989
      +/- 0.008. The differences of inner, outer, upper and lower boundaries of CTVpa
      and CTVan were (3.35 +/- 7.23) mm, (5.57 +/- 13.37) mm, (1.75 +/- 11.62) mm, and
      (11.25 +/- 4.07)mm, respectively. The cranial and medial boundaries had a
      negative correlation with CTVpa (P < 0.05 for all). CONCLUSIONS: The differences
      among the three methods in the delineation of whole breast target volume are
      statistically significant. The target volume delineated according to the
      glandular mammary tissue displayed by CT scan is significantly smaller than that
      by the other two methods. Combination of breast palpation and anatomical marks
      may be helpful in delineating the whole breast target volume is relatively
      reasonable at present.

PMID- 25564059
TI  - [Evaluation of intraductal papillary mucinous neoplasms of the pancreas on MDCT
      and MRI].
AB  - OBJECTIVE: The purpose of our study was to evaluate the predictive factors of the
      presence of invasive carcinoma associated with intraductal papillary mucinous
      neoplasm (IPMN) of the pancreas on MDCT and MRI. METHODS: Preoperative MDCT
      or/and MRI of 27 consecutive patients (19 men, 8 women, mean age 61.3 years) who
      had undergone surgical resection and had a pathological diagnosis of IPMN were
      retrospectively assessed. The type of ductal involvement, solid appearance of the
      lesion, location, tumor size of branch duct type and combined type lesions,
      maximum diameter of the tumor, caliber of the main pancreatic duct and the extent
      of the common bile duct dilatation were assessed on CT and MRI and correlated
      with the pathological findings of the invasive carcinoma. Two abdominal
      radiologists reviewed all the images, and when discrepancies of the findings were
      found, the consensus was reached by discussion. RESULTS: Pathological analysis
      revealed carcinoma in situ in two patients and invasive carcinoma in 19 patients
      arising from the IPMN. The type of ductal involvement (P = 0.038), a solid mass
      (P = 0.003) and the common bile duct dilatation ( >= 15 mm, P = 0.004) were
      correlated with the presence of associated invasive carcinoma. For the finding of
      solid and cystic mass in predicting invasive IPMN, the sensitivity was 66.7%
      (8/12) and specificity was 100.0% (8/8), and for bile duct diameter >= 15 mm, the
      sensitivity was 47.4% (9/19) and specificity was 100.0% (8/8). However, no
      association was found between the location of the lesion and associated invasive
      carcinoma. The caliber of the main pancreatic duct of patients with associated
      invasive carcinoma was significantly larger than that in the cases without
      invasive carcinoma (8.07 +/- 2.23 mm vs. 4.86 +/- 1.86 mm, P = 0.002). When using
      the main pancreatic duct dilatation >= 4 mm as the threshold, the sensitivity and
      specificity in predicting invasive IPMN were 94.7% (18/19) and 37.5% (3/8),
      respectively. For the branch duct type and combined type, the size of the tumor
      with associated invasive carcinoma was significantly larger than these without
      invasive carcinoma (41.35 +/- 12.58) mm vs. (23.76 +/- 8.06) mm (P = 0.003). When
      the maximum diameter was >= 40 mm, the sensitivity and specificity in predicting
      invasive IPMN were 50.0% (6/12) and 87.5% (7/8), respectively. CONCLUSIONS: The
      findings of CT and MRI are helpful to predict invasive carcinoma associated with
      IPMN, which may play an important role in the preoperative evaluation, surgical
      planning and predicting the prognosis of IPMN.

PMID- 25564060
TI  - [Correlation between characteristics of lymph node metastases and prognosis in
      pancreatic cancer treated with pancreaticoduodenectomy].
AB  - OBJECTIVE: To study the correlation between characteristics of lymph node
      metastases and prognosis in pancreatic cancer treated with
      pancreaticoduodenectomy. METHODS: The clinicopathological data of consecutive
      series of 122 patients who underwent resection for adenocarcinoma of the pancreas
      with lymphadenectomy in our hospital were reviewed in this study. The number of
      metastatic lymph nodes, lymph node metastasis ratio, lymph node levels, and other
      clinocopathological factors were analyzed by Kaplan-Meier method and Cox
      proportional hazard model, and their correlation with prognosis was also
      analyzed. RESULTS: 122 patients met the inclusion criteria and entered the study.
      There were 90 patients (73.8%) with lymph node metastases. Median (range)
      metastatic lymph node number was 7 (1-28) for the entire cohort, and median
      (range) metastatic lymph node ratio was 21.1% (3.6%-62.2%). The numbers of
      patients with lymph nodes metastases to levels 1, 2, 3 were 39 (43.3%), 40
      (44.4%), and 11 (12.2%), respectively. Univariate analysis suggested that the
      maximum diameter of tumor, lymph node metastases, number, ratio, level, distant
      metastases and adjuvant chemotherapy were significantly related to survival in
      the entire cohort (P < 0.05). The maximum diameter of tumor, lymph node
      metastasis number, ratio, level, and adjuvant chemotherapy were significantly
      related to the survival in node-positive patients (P < 0.05). Multivariate
      analysis suggested that the diameter of tumor >2 cm, lymph node metastases,
      metastatic lymph node number >2, ratio >20%, level >1, and without adjuvant
      chemotherapy were independent risk factors of survival in the entire cohort (P <
      0.05). The maximum diameter of tumor >2 cm, metastatic lymph node number >2,
      ratio >20%, level >1 and without adjuvant chemotherapy were independent risk
      factors of survival in node-positive patients (P < 0.05 for all). CONCLUSIONS:
      The three indexes, metastatic number, ratio and extent of lymph nodal involvement
      are statistically significant prognostic factors in pancreatic cancer, which can
      complement the existing lymph node metastasis staging. The standardized
      pancreaticoduodenectomy combined with proper lymphodenectomy provides an
      important basis for a correct prognostic evaluation.

PMID- 25564061
TI  - [Clinicopathological characteristics and prognosis of 11 patients with renal
      mucinous tubular and spindle cell carcinoma].
AB  - OBJECTIVE: To explore the clinicopathological features, treatment and prognosis
      of renal mucinous tubular and spindle cell carcinoma (MTSCC). METHODS: The
      clinicopathological data of eleven patients of pathologically confirmed renal
      MTSCC were reviewed retrospectively. Among the 11 patients, there were 4 males
      and 7 females with a mean age of 51.6 years (range, 24 to 81 years). Two patients
      presented with hematuria, one presented with lumbago and others were
      asymptomatic. RESULTS: The renal MTSCC was of hypovascular tumor in enhanced CT
      scan. Seven cases were treated with radical nephrectomy, and the other four with
      partial nephrectomy. The mean diameter of tumors was 4.4 cm. The TNM stages were
      as follows: pT1aN0M0 in 6, pT1bN0M0 in 3, pT2N0M0 in 2 cases. Histological
      examination of the tumors showed that they consisted of spindle cells arranged in
      tubular and trabecular patterns embedded in a myxoid stroma. No recurrence or
      metastasis was observed during the follow-up (median 41 months). CONCLUSIONS:
      MTSCC is a rare low-grade renal epithelial carcinoma with a relatively good
      prognosis. Preoperative CT scan is partly helpful for diagnosis and guiding
      decision making. Nephron-sparing surgery is recommended in most cases, especially
      in patients with small tumors.

PMID- 25564062
TI  - [Breast cancer brain metastases: clinical and prognostic characteristics of
      different biological subtypes].
AB  - OBJECTIVE: To analyze the clinical characteristics and survival depending on
      biological subtypes in breast cancer patients with brain metastases (BM).
      METHODS: A retrospective analysis was performed on 152 breast cancer patients
      with BM admitted to the Cancer Institute & Hospital, Chinese Academy of Medical
      Sciences from January 2003 to December 2012. Depending on the biological
      characteristics, these patients were divided into three subtypes: Luminal, human
      epidermal growth factor receptor 2 (HER-2)-overexpressing, and triple-negative
      subtypes. The clinicopathological characteristics, recurrence status, and
      prognostic factors were analyzed at the initial diagnosis. The systemic therapy
      after BM was further studied. RESULTS: Among the 152 patients, the number of
      Luminal, HER-2-overexpressing, and triple-negative breast cancer (TNBC) subtypes
      were 60, 53, and 39 cases, respectively. The median time from first recurrence to
      BM of all patients was 7.3 months, the median time of Luminal, HER-2
      overexpressing, and TNBC subtypes was 11.0 months, 9.6 months, and 5.5 months,
      respectively (P < 0.001). Compared with the TNBC subtype, BM occurred later in
      the HER-2-overexpressing subtype (P < 0.001). In the HER-2-overexpressing
      subtype, trastuzumab could delay the occurrence of BM in advanced breast cancer
      patients (17.1 vs. 1.7 months, P < 0.001, 95%CI 5.21-13.98). The median time of
      overall survival (OS) in the whole group was 56.5 months (7.5-240.2 months, 95%CI
      52.6-60.4). The median survival time of Luminal, HER-2-overexpressing and TNBC
      subtypes was 70.9 months, 53.9 months, and 40.9 months, respectively (P = 0.013).
      The median survival time of after BM was 11.5 months in the whole group, and the
      median survival time of Luminal, HER-2-overexpressing and TNBC subtypes was 11.2
      months, 12.7 months, and 11.6 months, respectively, with a difference of no
      statistical significance. Compared with non-BM as the first site, the patients
      with BM as the first site had a longer survival (14.8 months vs. 8.0 months, P =
      0.001). Systemic therapy could prolong the survival after BM. The median survival
      of chemotherapy, chemotherapy in combination with trastuzumab, and without
      systemic therapy was 13.6 months, 19.0 months, and 6.5 months, respectively (P =
      0.043). CONCLUSIONS: The survival after BM is influenced by biological subtypes.
      Compared with the Luminal subtype, brain meatastases occurr earlier in HER-2
      overexpressing and TNBC subtypes. Trastuzumab can delay the occurrence of BM from
      advanced breast cancer, and systemic therapy can improve the survival of patients
      after brain metastasis.

PMID- 25564063
TI  - [Clinical analysis and prognostic factors in 106 patients with stage Ia-IIb
      cervical cancer with pulmonary metastasis].
AB  - OBJECTIVE: To investigate the clinical characteristics and prognostic factors for
      patients with stage Ia-IIb cervical cancer with pulmonary metastasis (CCMP).
      METHODS: Clinical information of 106 patients with stage Ia-IIb cervical cancer
      with lung metastases admitted in the Chinese Academy of Medical Sciences Cancer
      Hospital from January 1999 to June 2013 was collected. The efficacy of different
      therapeutic methods for lung metastases was compared and relevant prognostic
      factors were analyzed. RESULTS: Pulmonary metastases were detected in 89 (83.9%)
      out of a total of 106 patients within 2 years after initial treatment of cervical
      cancer. The median disease-free interval (DFI) of the 106 patients was 13 months.
      The median survival after CCMP was 18 months, with 2-year and 5-year survival
      rates of 37.7% and 7.5%, respectively. Metastases were mainly distributed in the
      inferior lobe of right lung. The surgical treatment was proven to be clinically
      effective in both unilateral and bilateral CCMP. The response rate was 60.2% in
      patients choosing non-operative treatment. The univariate analysis showed that
      pathological type of cervix carcinoma, low degree of differentiation, scope of
      pulmonary metastasis and whether CCMP simultaneously accompanied with other parts
      of recurrence were closely related to the prognosis, while the differentiation of
      cervical tumor was an independent prognostic factor drawn from multivariate
      regression analysis. CONCLUSIONS: Regular CT lung screening is recommended for
      patients with stage Ia-IIb cervical cancer during their follow-up period. Both
      operative and non-operative treatments are feasible therapeutic methods for CCMP.
      But surgical resection is strictly restricted to certain operative indications.
      Ia-IIb stage cervical cancer of low differentiation has poorer prognosis after
      lung metastasis.

PMID- 25564064
TI  - [Clinical observation of the salvage therapy using pegylated recombinant human
      granulocyte colony stimulating factor for grade IV neutropenia induced by
      concurrent chemoradiotherapy].
AB  - OBJECTIVE: To investigate the efficacy and safety of pegylated recombinant human
      granulocyte colony stimulating factor (PEG-rhG-CSF) in the salvage therapy for
      the grade IV neutropenia induced by concurrent chemoradiotherapy, and to provide
      evidence for its clinical rational application. METHODS: 114 malignant tumor
      patients suffered with grade IV neutropenia induced by concurrent
      chemoradiotherapy were treated in the following groups. In the P-50 group, 42
      patients received a single subcutaneous injection of 50 ug/kg PEG-rhG-CSF. In the
      P-100 group, 30 patients received a single subcutaneous injection of 100 ug/kg
      PEG-rhG-CSF. In the P+R group, 22 patients received a single subcutaneous
      injection of 50 ug/kg PEG-rhG-CSF and multiple subcutaneous injections of 5
      ug*kg(-1)*d(-1) rhG-CSF, until the absolute neutrophil count (ANC) >=
      2.0*10(9)/L. In the R group, 20 patients received multiple subcutaneous
      injections of 5 ug*kg(-1)*d(-1) rhG-CSF, until ANC >= 2.0*10(9)/L. The P-50, P
      100 and P+R groups were experimental groups, and the R group was defined as
      control group. In each group, the neutrophil proliferation rate and the
      neutrophil counts at different time points, the period of neutropenia symptom
      relief, and the rate of adverse reactions induced by above drugs were analyzed.
      RESULTS: Both neutrophil proliferation rates and neutrophil counts in the
      patients of experimental groups at different time points were significantly
      higher than those in the control group. In the experimental groups the period of
      the clinical effect began in 12-24 hours, and the conditions of neutropenia were
      improved in 36 hours. In the experimental groups, the period of the symptom
      relief such as fever and skeletal muscle pain was (30.00 +/- 7.48) hours and
      (30.00 +/- 5.10) hours, respectively, significantly shorter than (72.00 +/-
      17.89) hours and (59.00 +/- 11.46) hours in the control group (P < 0.05). The
      adverse drug reaction rate was 26.1% in the experimental groups and 25.0% in the
      control group (P > 0.05). CONCLUSIONS: For the treatment of grade IV neutropenia
      induced by concurrent chemoradiotherapy, PEG-rhG-CSF is effective and safe. The
      recommend dose of this drug for the salvage therapy for those patients is a
      single hypodermal injection of 50 ug/kg. Usually it becomes effective in 12-24
      hours.

PMID- 25564065
TI  - [Relationship between female breast cancer incidence and the socioeconomic status
      in Beijing].
AB  - OBJECTIVE: To explore the relationship between female breast cancer incidence and
      the socioeconomic status in Beijing. METHODS: The data of female breast cancer
      patients of Beijing residents diagnosed between 2001 and 2010 were sorted from
      the population-based surveillance database of Beijing Cancer Registry.28, 184
      cases were included, covering 58, 427, 396 female person-years. Incidence rates,
      rates adjusted by world population in each year, mean and median age at diagnosis
      and the peak age group were calculated. JoinPoint software was applied to
      calculate the incidence trend and the annual percentage of changing (APC). Using
      the data from the Beijing Statistical Yearbook in 1991-2000, we calculated the
      gross output value of industry, the average wage of Beijing residents, the food
      expenditure level and the average wage in different districts in Beijing. The
      relationship between female breast cancer incidence, the average age (mean,
      median and the peak age groups) at diagnosis and the socioeconomic status in the
      last 10 years was also calculated. RESULTS: From 2001 to 2010, the incidence rate
      of female breast cancer in Beijing rose from 32.03/100 000 to 58.10/100 000, a
      total increase of 81.39% over the last 10 years and the annual percentage change
      was 5.76%, after adjusted by world population (APC = 5.76%, P < 0.05). The
      relationships between female breast cancer incidence from 2001-2010 and the gross
      output value of industry, the average wage of Beijing residents, the food
      expenditure level in 1991-2000 were significant (P < 0.05). The Pearson
      correlation coefficients were 0.928, 0.957, and 0.982, respectively. In terms of
      the data in different districts in Beijing, the relationships between the average
      age (mean, median and the peak age group) in 2001-2010 and the average wage of
      Beijing residence in 1991-2000 were also significant with a correlation
      coefficient of 0.806,0.785 and 0.754, respectively (P < 0.05). CONCLUSIONS: The
      increase of female breast cancer incidence rate in Beijing is positively
      correlated with the socioeconomic status, especially with the food expenditure
      level of Beijing residents over the last 10 years. The higher the economic
      development, the peak age of onset of female breast cancer is more postponed.

PMID- 25564066
TI  - [Consensus statement on the diagnosis and treatment of pancreatic endocrine
      tumors].

PMID- 25564067
TI  - Large-scale evaluation of experimentally determined DNA G+C contents with whole
      genome sequences of prokaryotes.
AB  - Historically, DNA G+C content has played a critical role in the description of
      bacterial and archaeal species. Despite its importance in prokaryote taxonomy,
      its accuracy has been questioned due to methodological heterogeneity and
      measurement errors of conventional methods. Here we investigated the extent of
      accuracy of experimentally determined DNA G+C contents by comparing the reference
      values calculated from whole genome sequences. The large-scale comparison
      revealed that G+C contents determined by high-performance liquid chromatography
      and buoyant density centrifugation methods were more similar to the genome
      derived reference values than those generated by thermal denaturation method.
      However, there was a substantial degree of discrepancy in DNA G+C contents
      between values obtained by conventional methods and genome-derived reference
      values. The majority of the differences between them fell out of the acceptable
      range (i.e. 1 mol% G+C content difference) for species delimitation of
      prokaryotes. In contrast, when average nucleotide identity (ANI) was correlated
      to G+C difference among genomes, most G+C difference was confined to less than 1%
      within species. Therefore, erroneous conventional methods are not meaningful in
      the description of bacterial and archaeal species. For taxonomic purposes, DNA
      G+C content should be determined by calculating directly from high-quality genome
      sequences with at least 16* or higher sequencing depth of coverage.

PMID- 25564069
TI  - Predictability of preoperative 18F-FDG PET for histopathological differentiation
      and early recurrence of primary malignant intrahepatic tumors.
AB  - OBJECTIVE: The limited studies with 18F-fluorodeoxyglucose (18F-FDG)-PET reported
      results and interpretations that differed between hepatocellular carcinoma (HCC)
      and intrahepatic cholangiocarcinoma (IHCC). We investigated the correlation
      between preoperative PET results and postoperative prognosis, including early
      (time-to-recurrence<6 months) tumor recurrence, and histopathological tumor
      differentiation in patients who had undergone surgery for primary malignant
      intrahepatic tumors, including HCC and IHCC. MATERIALS AND METHODS: We
      retrospectively reviewed 357 patients who had undergone curative surgery for
      malignant hepatic tumors, including primary HCC or IHCC, other than Klatskin
      tumors at a tertiary academic hospital between January 2005 and June 2012. All
      patients had undergone an 18F-FDG PET/computed tomography scan preoperatively and
      the maximum standardized uptake value of the tumor (max SUV tumor) and the tumor
      to-nontumor SUV ratio (TNR) were calculated from 18F-FDG uptake.
      Histopathological differentiation grading was confirmed postoperatively. RESULTS:
      Among the patients, 115 cases with primary malignant intrahepatic tumors
      fulfilled the inclusion criteria. On univariate analysis, preoperative max SUV
      tumor and TNR showed a correlation with the overall and early tumor recurrence of
      HCC, but only max SUV tumor was associated with overall and early recurrence of
      IHCC (P<0.05). When considering postoperative histopathological differentiation,
      a correlation between max SUV tumor and TNR with HCC and between max SUV tumor
      and IHCC was found (P<0.05). However, on multivariate analysis, only early
      recurrence was associated with TNR in HCC and with max SUV tumor in IHCC.
      CONCLUSION: A preoperative 18F-FDG PET scan can be considered a useful reference
      for postoperative tumor recurrence and histopathological differentiation in cases
      of primary malignant intrahepatic tumors. 18F-FDG PET scan results should be
      interpreted separately for malignant liver tumors.

PMID- 25564068
TI  - Optical coherence tomography (OCT) for detection of macular oedema in patients
      with diabetic retinopathy.
AB  - BACKGROUND: Diabetic macular oedema (DMO) is a thickening of the central retina,
      or the macula, and is associated with long-term visual loss in people with
      diabetic retinopathy (DR). Clinically significant macular oedema (CSMO) is the
      most severe form of DMO. Almost 30 years ago, the Early Treatment Diabetic
      Retinopathy Study (ETDRS) found that CSMO, diagnosed by means of stereoscopic
      fundus photography, leads to moderate visual loss in one of four people within
      three years. It also showed that grid or focal laser photocoagulation to the
      macula halves this risk. Recently, intravitreal injection of antiangiogenic drugs
      has also been used to try to improve vision in people with macular oedema due to
      DR.Optical coherence tomography (OCT) is based on optical reflectivity and is
      able to image retinal thickness and structure producing cross-sectional and three
      dimensional images of the central retina. It is widely used because it provides
      objective and quantitative assessment of macular oedema, unlike the subjectivity
      of fundus biomicroscopic assessment which is routinely used by ophthalmologists
      instead of photography. Optical coherence tomography is also used for
      quantitative follow-up of the effects of treatment of CSMO. OBJECTIVES: To
      determine the diagnostic accuracy of OCT for detecting DMO and CSMO, defined
      according to ETDRS in 1985, in patients referred to ophthalmologists after DR is
      detected. In the update of this review we also aimed to assess whether OCT might
      be considered the new reference standard for detecting DMO. SEARCH METHODS: We
      searched the Cochrane Database of Systematic Reviews (CDSR), the Database of
      Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database
      (HTA) and the NHS Economic Evaluation Database (NHSEED) (The Cochrane Library
      2013, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed
      Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2013),
      EMBASE (January 1950 to June 2013), Web of Science Conference Proceedings
      Citation Index - Science (CPCI-S) (January 1990 to June 2013), BIOSIS Previews
      (January 1969 to June 2013), MEDION and the Aggressive Research Intelligence
      Facility database (ARIF). We did not use any date or language restrictions in the
      electronic searches for trials. We last searched the electronic databases on 25
      June 2013. We checked bibliographies of relevant studies for additional
      references. SELECTION CRITERIA: We selected studies that assessed the diagnostic
      accuracy of any OCT model for detecting DMO or CSMO in patients with DR who were
      referred to eye clinics. Diabetic macular oedema and CSMO were diagnosed by means
      of fundus biomicroscopy by ophthalmologists or stereophotography by
      ophthalmologists or other trained personnel. DATA COLLECTION AND ANALYSIS: Three
      authors independently extracted data on study characteristics and measures of
      accuracy. We assessed data using random-effects hierarchical sROC meta-analysis
      models. MAIN RESULTS: We included 10 studies (830 participants, 1387 eyes),
      published between 1998 and 2012. Prevalence of CSMO was 19% to 65% (median 50%)
      in nine studies with CSMO as the target condition. Study quality was often
      unclear or at high risk of bias for QUADAS 2 items, specifically regarding study
      population selection and the exclusion of participants with poor quality images.
      Applicablity was unclear in all studies since professionals referring patients
      and results of prior testing were not reported. There was a specific 'unit of
      analysis' issue because both eyes of the majority of participants were included
      in the analyses as if they were independent.In nine studies providing data on
      CSMO (759 participants, 1303 eyes), pooled sensitivity was 0.78 (95% confidence
      interval (CI) 0.72 to 0.83) and specificity was 0.86 (95% CI 0.76 to 0.93). The
      median central retinal thickness cut-off we selected for data extraction was 250
      um (range 230 um to 300 um). Central CSMO was the target condition in all but two
      studies and thus our results cannot be applied to non-central CSMO.Data from
      three studies reporting accuracy for detection of DMO (180 participants, 343
      eyes) were not pooled. Sensitivities and specificities were about 0.80 in two
      studies and were both 1.00 in the third study.Since this review was conceived,
      the role of OCT has changed and has become a key ingredient of decision-making at
      all levels of ophthalmic care in this field. Moreover, disagreements between OCT
      and fundus examination are informative, especially false positives which are
      referred to as subclinical DMO and are at higher risk of developing clinical
      CSMO. AUTHORS' CONCLUSIONS: Using retinal thickness thresholds lower than 300 um
      and ophthalmologist's fundus assessment as reference standard, central retinal
      thickness measured with OCT was not sufficiently accurate to diagnose the central
      type of CSMO in patients with DR referred to retina clinics. However, at least
      OCT false positives are generally cases of subclinical DMO that cannot be
      detected clinically but still suffer from increased risk of disease progression.
      Therefore, the increasing availability of OCT devices, together with their
      precision and the ability to inform on retinal layer structure, now make OCT
      widely recognised as the new reference standard for assessment of DMO, even in
      some screening settings. Thus, this review will not be updated further.

PMID- 25564071
TI  - Deriving global quantitative tumor response parameters from 18F-FDG PET-CT scans
      in patients with non-Hodgkin's lymphoma.
AB  - OBJECTIVES: The aim of the study was to address the need for quantifying the
      global cancer time evolution magnitude from a pair of time-consecutive positron
      emission tomography-computed tomography (PET-CT) scans. In particular, we focus
      on the computation of indicators using image-processing techniques that seek to
      model non-Hodgkin's lymphoma (NHL) progression or response severity. MATERIALS
      AND METHODS: A total of 89 pairs of time-consecutive PET-CT scans from NHL
      patients were stored in a nuclear medicine station for subsequent analysis. These
      were classified by a consensus of nuclear medicine physicians into progressions,
      partial responses, mixed responses, complete responses, and relapses. The cases
      of each group were ordered by magnitude following visual analysis. Thereafter, a
      set of quantitative indicators designed to model the cancer evolution magnitude
      within each group were computed using semiautomatic and automatic image
      processing techniques. Performance evaluation of the proposed indicators was
      measured by a correlation analysis with the expert-based visual analysis.
      RESULTS: The set of proposed indicators achieved Pearson's correlation results in
      each group with respect to the expert-based visual analysis: 80.2% in
      progressions, 77.1% in partial response, 68.3% in mixed response, 88.5% in
      complete response, and 100% in relapse. In the progression and mixed response
      groups, the proposed indicators outperformed the common indicators used in
      clinical practice [changes in metabolic tumor volume, mean, maximum, peak
      standardized uptake value (SUV mean, SUV max, SUV peak), and total lesion
      glycolysis] by more than 40%. CONCLUSION: Computing global indicators of NHL
      response using PET-CT imaging techniques offers a strong correlation with the
      associated expert-based visual analysis, motivating the future incorporation of
      such quantitative and highly observer-independent indicators in oncological
      decision making or treatment response evaluation scenarios.

PMID- 25564070
TI  - The early plasma concentration of 51Cr-EDTA in patients with cirrhosis and
      ascites: a comparison of three models.
AB  - OBJECTIVES: The aim of the study was to determine which of three two-parameter
      fitting functions (exponential, linear-log, and negative-power function of time)
      most accurately models early chromium-51-EDTA (51Cr-EDTA) plasma concentration
      data prior to 120 min in patients with cirrhosis and ascites and understand how
      these fitting functions affect the calculation of the area under the plasma
      concentration curve (AUC). METHODS: A bolus, antecubital intravenous injection of
      2.6 MBq of 51Cr-EDTA was given to 13 patients with cirrhosis and ascites. Up to
      16 blood samples were drawn at time points ranging from 5 to 1440 min following
      injection. The concentration data prior to 120 min were used as reference data.
      Early time concentration values, estimated by fitting exponential, linear-log,
      and negative-power functions of time to the time samples at 120, 180, and 240
      min, were then compared with reference data. The AUC was calculated for each
      patient using the exponential, Brochner-Mortensen-corrected exponential, and
      linear-log functions, and these values were compared. RESULTS: The withheld,
      observed plasma concentrations were (a) most accurately estimated by linear-log
      functions (Wilcoxon P=0.4548), (b) significantly underestimated by exponential
      functions (Wilcoxon P=0.0002), and (c) significantly overestimated by negative
      power functions (Wilcoxon P=0.0034). The relative errors when ranked from best to
      worst were those for the linear-log (12.0%, 9.0%), exponential (22.9%, 14.2%),
      and negative-power (31.9%, 48.4%) functions of time, respectively (median,
      interquartile range). For each patient, the values for AUC calculated by the
      exponential function differed significantly (range=3.4-15.3%, median=8.3%) from
      those calculated by the corrected Brochner-Mortensen exponential, as to a lesser
      extent did those values calculated using linear-log functions (range=0.4-8.0%,
      median=3.0%). CONCLUSION: In patients with cirrhosis, linear-log functions were
      significantly more accurate than exponential or power functions in estimating
      early time plasma concentrations (<120 min). However, the improved linear-log
      early time plasma concentration model does not provide as much correction to the
      total AUC as does the corrected Brochner-Mortensen exponential method. This is
      likely because of the large contribution of late time data to the AUC, and future
      work is suggested to explore the late time fit problem.

PMID- 25564072
TI  - What drives "fibrinolysis"?
AB  - The timely removal of blood clots and fibrin deposits is essential in the
      regulation of haemostasis. This is achieved by the fibrinolytic system, an
      enzymatic process that regulates the activation of plasminogen into its
      proteolytic form, plasmin. This is a self-regulated event as the very presence of
      fibrin initiates plasminogen activation on the fibrin surface due to the
      presentation of exposed C-terminal lysine residues in fibrin that allow
      plasminogen to position itself via its lysine binding sites and to be more
      efficiently cleaved by tissue-type plasminogen activator (t-PA). Hence fibrin,
      the ultimate substrate of plasmin during fibrinolysis, is indeed an essential
      cofactor in the cascade. What has now come to light is that the fibrinolytic
      system is not solely designed to eliminate fibrin. Indeed, it is a broad acting
      system that processes a variety of proteins, including many in the brain where
      there is no fibrin. So what drives t-PA-mediated plasminogen activation when
      fibrin is not available? This review will describe the broadening role of the
      fibrinolytic system highlighting the importance of fibrin and other key proteins
      as facilitators during t-PA-mediated plasminogen activation. 

PMID- 25564073
TI  - Professor Daniele Nuti and his academic career.

PMID- 25564074
TI  - Behavior of the human translational vestibulo-ocular reflex during simultaneous
      head translation and rotation.
AB  - BACKGROUND: During head translations, vestibular eye movements are ~ 60% of those
      required to hold the line of sight on target but, during translation of the
      orbits due to head rotation about an eccentric axis, the eyes are held %eye on
      target. OBJECTIVE: To resolve this paradoxical behavior of vestibulo-ocular
      reflexes. METHODS: Subjects sat on a moving platform viewing a near target and
      were: (1) rotated en bloc in yaw about a vertical axis centered on the head at 1
      Hz; (2) rotated with their head displaced ~ 10 cm anterior (eccentric rotation)
      at 1 Hz; (3) translated along the inter-aural axis at 1.9 Hz; (4) rotated with
      the head centered at 1 Hz while they were translated along the inter-aural axis
      at 1.9 Hz. We calculated compensation ratio (CR): Eye velocity/eye velocity
      geometrically required to hold the eye on target. RESULTS: During yaw, mean CR
      was 0.88 and during eccentric rotation CR was 0.93. During translation at 1.9 Hz,
      CR was 0.65. During combined rotation at 1.0 Hz and translation at 1.9 Hz, CR was
      0.81 for head rotations and 0.74 for head translations. CONCLUSIONS: Translations
      of the orbits due to head rotation are better compensated for than translations
      of the orbits due to head translation. These different behaviors may be
      determined by context, the important difference being whether the subject is
      moving through the environment.

PMID- 25564075
TI  - The first attack of Meniere's disease: a study through SVV perception, clinical
      and pathogenetic implications.
AB  - This is a study of Subjective Visual Vertical (SVV) perception during acute
      attacks of Meniere's disease (MD) with comparative evaluation of concurrent
      nystagmus. We studied 21 patients with unilateral MD during the acute phase and 7
      days later. Of the nine patients with an initial attack of MD, seven had an
      alteration of SVV perception and of these, three indicated a match with canal
      functional signs, while four patients showed an opposite trend of SVV perception
      relative to the spontaneous nystagmus. Nine of the 12 patients with definite MD
      had a pathological SVV perception always in correspondence with the same type of
      canal event. At 1-week control, no patient with an initial MD attack had
      alteration of SVV perception, whereas 5 patients with definite MD presented a
      pathological SVV perception toward the affected side. In the course of acute
      attacks of unilateral MD, clinical manifestations may include otolithic
      involvement and this may have an opposite trend compared to concomitant canal
      signs, especially during initial attacks. This behavior allows us to distinguish
      clinical signs of maculo-canal "correspondence" and "dissociation" with a
      significant prevalence of the second indication in those subjects with an initial
      MD attack. 

PMID- 25564076
TI  - Lateral canal BPPV with Pseudo-Spontaneous Nystagmus masquerading as vestibular
      neuritis in acute vertigo: a series of 273 cases.
AB  - OBJECTIVE: To investigate the incidence of Lateral Semicircular Canal BPPV (LSC
      BPPV) with Pseudo-Spontaneous Nystagmus in patients preliminarily diagnosed for
      vestibular neuritis in the Emergency Department (ED). METHODS: Retrospective
      study of 273 patients with acute vertigo and persistent horizontal nystagmus in
      upright position (male 110, female 163, 14-93 years old) observed over four
      years. All the patients were checked for any nystagmus modification by performing
      the Head Pitch Test (HPT) in the upright position. RESULTS: The HPT modified the
      beating direction of the persistent horizontal nystagmus in 56 of the 273
      examined patients. The positioning tests subsequently confirmed the diagnosis of
      LSC BPPV in all those 56 patients. There were 37 geotropic variants and 19
      apogeotropic variants and all of them were successfully treated by performing
      liberatory manoeuvres in the course of the same session. CONCLUSION: Performing
      the HPT in the upright position helps to differentiate a direction fixed
      nystagmus from a direction changing one, and in so doing, to make the
      differential diagnosis between vestibular neuritis and LSC BPPV, achieving the
      goal of successfully treating LSC BPPV in the first session.

PMID- 25564077
TI  - Impaired vestibulo-ocular reflex (VOR) in spinocerebellar ataxia type 3 (SCA3):
      bedside and search coil evaluation.
AB  - Vestibulo-Ocular Reflex (VOR) abnormalities in cerebellar ataxias are a matter of
      renewed interest. We have previously reported vestibular areflexia in a group of
      Yemenite-Jews with Spinocerebellar Ataxia Type 3 (SCA3) who had clear bilateral
      pathological horizontal Head Impulse Test (HIT). The objective of this study was
      to evaluate the VOR of ten SCA3 patients who have variable bedside HIT responses
      by recording their eye movements using magnetic search coils and to correlate
      these results with their clinical and genetic data. Eight out of the ten patients
      have abnormal horizontal HIT detected by both clinical bedside examination and
      laboratory tests. Results of bedside HIT testing were significantly correlated
      with the VOR gain recorded using magnetic search coils. No significant
      correlations were found between VOR gain and other clinical or genetic data. Our
      study confirms the presence of defective VOR in SCA3 patients and corroborates
      the useful of the HIT as a reliable bedside test for diagnosis of VOR deficits. 

PMID- 25564078
TI  - Amplitude and frequency prediction in the translational vestibulo-ocular reflex.
AB  - The goal of this study was to assess the effect of amplitude and frequency
      predictability on the performance of the translational vestibulo-ocular reflex
      (tVOR). Eye movements were recorded in 5 subjects during continuous vertical
      translation that consisted of a series of segments with: 1) 3 amplitudes at
      constant frequency (2 Hz) or 2) 3 different frequencies (1.6, 2, 2.5 Hz).
      Stimulus changes were presented in a pseudo-random order. We found that there was
      little change in the tVOR immediately after an unexpected stimulus change, as if
      eye velocity were being driven more by an expectation based on previous steady
      state motion than by current head translation. For amplitude transitions, only
      about 30% of the eventual response change was seen in the first half cycle.
      Similarly, a sudden change in translation frequency did not appear in eye
      velocity for 70 ms, compared to a 8 ms lag during similar yaw rotation. Finally,
      after a sudden large decrease in frequency, the eyes continued to track at the
      original higher frequency, resulting initially in an anti-compensatory tVOR
      acceleration. Our results elucidate further the complexity of the tVOR and show
      that motion prediction based on prior experience plays an important role in its
      response. 

PMID- 25564079
TI  - Selective otolith dysfunctions objectively verified.
AB  - Vertigo and vigorous horizontal spontaneous nystagmus in a presenting patient is
      usually taken to indicate unilaterally reduced horizontal canal function. However
      here we report results which question that presumption. In three such patients
      with an acute vestibular syndrome, complete testing of all peripheral vestibular
      sense organs using new tests of canal and otolith function (vHIT and VEMPs)
      showed that semicircular canal function was normal, but that there were
      unilateral otolithic deficits which probably caused their acute syndrome. 

PMID- 25564080
TI  - The role of the thalamus in the human subcortical vestibular system.
AB  - Most of our knowledge concerning central vestibular pathways is derived from
      animal studies while evidence of the functional importance and localization of
      these pathways in humans is less well defined. The termination of these pathways
      at the thalamic level in humans is even less known. In this review we summarize
      the findings concerning the central subcortical vestibular pathways in humans and
      the role of these structures in the central vestibular system with regard to
      anatomical localization and function. Also, we review the role of the thalamus in
      the pathogenesis of higher order sensory deficits such as spatial neglect, pusher
      syndrome or thalamic astasia and the correlation of these phenomena with findings
      of a vestibular tone imbalance at the thalamic level. By highlighting thalamic
      structures involved in vestibular signal processing and relating the different
      nomenclatures we hope to provide a base for future studies on thalamic sensory
      signal processing. 

PMID- 25564081
TI  - Comorbidities in vestibular migraine.
AB  - A growing body of clinical and epidemiological evidence supports a specific
      relationship between vestibular symptoms and migraine. Without a biomarker or
      complete understanding of pathophysiology, diagnosis of vestibular migraine (VM)
      currently depends upon symptoms in two dimensions: episodic vestibular symptoms
      temporally related to migraine symptoms. The Barany Society and the International
      Headache Society have recently developed consensus diagnostic criteria. However,
      many issues remain unsettled, including the type, duration, and timing of
      vestibular symptoms related to headache that should be required for diagnosing
      VM. This paper focuses on the challenging third dimension of comorbidity, a
      frequent cause of diagnostic uncertainty that may confound clinical application
      and research validation of VM criteria. Several other neurotologic conditions
      occur more frequently in migraineurs than controls, including benign paroxysmal
      positional vertigo, Meniere's disease, and motion sickness. Patients with VM also
      have high rates of chronic subjective dizziness, which may be associated with
      anxious, introverted temperaments that can affect clinical presentation and
      treatment response. Broadly inclusive studies of well-characterized patients with
      other neurotologic and psychiatric comorbidities are needed to fully understand
      how vestibular symptoms and migraine interact in order to truly validate
      vestibular migraine, distill its essential features, define its boundaries, and
      characterize overlapping comorbidities. 

PMID- 25564082
TI  - Acute VOR gain differences for outward vs. inward head impulses.
AB  - BACKGROUND: Vestibular rehabilitation is a sub-specialization within the practice
      of physical therapy that includes treatments designed to reduce gaze instability.
      Gaze stability exercises are commonly given for head rotations to the left and
      right, even in subjects with one healthy vestibular system (as in unilateral
      loss). Few studies have investigated the difference in the angular vestibular
      ocular reflex gain (aVOR) measured in the acute phase after deafferentation for
      ipsilesional head rotations that move the head away from center or towards
      center. OBJECTIVE: The purpose of this study was to compare differences in acute
      aVOR gain when the head was passively rotated outward from an initially centered
      position (neck neutral) versus the head being rotated inward. METHODS: We
      recorded head and eye velocity using video head impulse test equipment in
      patients with unilateral vestibular pathology scheduled for tumor resection via
      retrosigmoid approach (n=5) or labyrinthectomy due to Meniere's disease (n=2).
      RESULTS: We found 1) no difference in the ipsilesional aVOR gain for inward or
      outward directed head impulse rotations and 2) head velocity is inversely
      correlated with aVOR gain for ipsilesional but not contralesional rotations.
      CONCLUSIONS: Bedside testing of the ipsilesional aVOR following acute vestibular
      ablation can be done with head impulse rotations to either side. In the acute
      stages, physical therapists should prescribe ipsilesional and contralesional gaze
      stability exercises.

PMID- 25564083
TI  - Assessment of cerebral dopamine D 2/3 formula-receptors in patients with
      bilateral vestibular failure.
AB  - BACKGROUND: Absence of peripheral vestibular input in bilateral vestibular
      failure (BVF) has been suggested to induce plastic reorganization in various
      brain regions. Among several neurotransmitters, dopamine is known to play a key
      role in cortico-striatal-sensorimotor processing. However, the role of dopamine
      in vestibular plasticity is scantly documented. OBJECTIVE: Assessment of D 2/3
      formula-receptors in patients with BVF. METHODS: D 2/3 formula-receptor-PET using
      [18F]fallypride and MRI examinations were performed in 12 BVF-patients and 13
      healthy controls. RESULTS: BVF-patients showed reduced D 2/3 formula-receptor
      availability (approximately 40%) in the temporo-parieto-occipital cortex
      bilaterally, including the multisensory vestibular cortex and visual motion
      sensitive areas (MT/MST), as well as in the striatum and the right thalamus.
      Longer illness duration was associated with bilaterally lower D 2/3 formula
      receptor availability in the middle/superior temporal gyrus (GTm/s). D 2/3
      formula-receptor availability in the right GTm/s and bilateral insula decreased
      with severity of symptoms. BVF-patients with oscillopsia showed reduced D 2/3
      formula-receptor availability in the right MT/MST and midbrain tectum.
      CONCLUSIONS: Reduced D 2/3 formula-receptor availability in multisensory
      vestibular cortical network areas and basal ganglia may indicate a receptor down
      regulation due to the lack of peripheral vestibular input. The more pronounced
      decline in D 2/3 formula-receptor availability in the multisensory vestibular
      cortex in patients with prolonged illness suggests the occurrence of progressive
      changes in dopamine transmission.

PMID- 25564084
TI  - Typical and atypical benign paroxysmal positional vertigo: literature review and
      new theoretical considerations.
AB  - Atypical variants of benign paroxysmal positional vertigo (BPPV) are often
      encountered and frequently confusing. The authors present a hypothetical
      framework that accounts for all classical patterns of BPPV and several unusual
      variants such as BPPV without nystagmus, BPPV with downbeat nystagmus and BPPV
      with paradoxically direction-changing nystagmus. The authors introduce new
      concepts, such as "ipsicanal switch" and "horizontal short arm canalolithiasis"
      and suggest that their use may improve diagnosis and treatment in everyday
      clinical practice. The possible consequences of saccular otoconia detachment are
      reviewed according to the literature. 

PMID- 25564085
TI  - Gaze stabilization in chronic vestibular-loss and in cerebellar ataxia:
      interactions of feedforward and sensory feedback mechanisms.
AB  - During gaze shifts, humans can use visual, vestibular, and proprioceptive
      feedback, as well as feedforward mechanisms, for stabilization against active and
      passive head movements. The contributions of feedforward and sensory feedback
      control, and the role of the cerebellum, are still under debate. To quantify
      these contributions, we increased the head moment of inertia in three groups (ten
      healthy, five chronic vestibular-loss and nine cerebellar-ataxia patients) while
      they performed large gaze shifts to flashed targets in darkness. This induces
      undesired head oscillations. Consequently, both active (desired) and passive
      (undesired) head movements had to be compensated for to stabilize gaze. All
      groups compensated for active and passive head movements, vestibular-loss
      patients less than the other groups (P < 0.001, passive/active compensatory
      gains: vestibular-loss 0.23 +/- 0.09/0.43 +/- 0.12, healthy 0.80 +/- 0.17/0.83 +/
      0.15, cerebellar-ataxia 0.68 +/- 0.17/0.77 +/- 0.30, mean +/- SD). The
      compensation gain ratio against passive and active movements was smaller than one
      in vestibular-loss patients (0.54 +/- 0.10, P=0.001). Healthy and cerebellar
      ataxia patients did not differ in active and passive compensation. In summary,
      vestibular-loss patients can better stabilize gaze against active than against
      passive head movements. Therefore, feedforward mechanisms substantially
      contribute to gaze stabilization. Proprioception alone is not sufficient (gain
      0.2). Stabilization against active and passive head movements was not impaired in
      our cerebellar ataxia patients. 

PMID- 25564086
TI  - Fear of heights freezes gaze to the horizon.
AB  - Fear of heights is elicited by a glance into an abyss. However, the visual
      exploration behavior of fearful subjects at height has not been analyzed yet. We
      investigated eye- and head movements, i.e. visual exploration behavior, of
      subjects susceptible to fear of heights during exposure to a visual cliff. The
      movements of eyes and head were recorded in 19 subjects susceptible to fear of
      heights and 18 controls while standing still on an emergency balcony 20 meters
      above ground level for periods of 30 seconds. Participants wore mobile, infrared
      eye-tracking goggles with inertial sensors for recording head movements.
      Susceptibles exhibited fewer and smaller-amplitude eye-in-head saccades with
      fixations of longer duration. Spontaneous head movements were reduced by 49% in
      susceptibles with a significantly lower mean absolute angular velocity (5.3
      degrees /s vs. 10.4 degrees /s), and all three dimensions (yaw, pitch and roll)
      were equally affected. Gaze-in-space--which indicates exploration by coordinated
      eye-head movements--covered a smaller total area of the visual scene (explored
      horizontal angle: 19 degrees  vs. 32 degrees , vertical: 9 degrees  vs. 17
      degrees ). We hypothesize that the susceptibles suppress eye and head movements
      to alleviate fear of heights. However, this behavior has the potential
      disadvantage of impairing the visual stabilization of postural balance.

PMID- 25564087
TI  - Combined peripheral and central vestibulopathy.
AB  - Diagnosis of central vestibulopathy remains a challenge when it is associated
      with peripheral vestibular dysfunction because neurotological findings from
      peripheral vestibulopathy may overshadow those from central vestibular
      involvements. To define the characteristics of disorders involving both
      peripheral and central vestibular structures, we classified the combined
      vestibulopathies into four types according to their vestibular manifestations,
      and describe a typical case in each subtype. Infarction involving the territory
      of anterior inferior cerebellar artery is the most common cause of acute
      unilateral cases, whereas tumors involving the cerebellopontine angle should be
      of prime suspicion in patients with chronic unilateral ones. Wernicke
      encephalopathy was most common in patients with acute bilateral combined
      vestibulopathy while degenerative disorders should be considered in chronic
      bilateral ones. Since the head impulse test (HIT) is mostly positive in combined
      vestibulopathy, signs of central vestibular dysfunction other than negative HIT
      should be sought carefully even in patients with obvious clinical or laboratory
      features of peripheral vestibulopathy. 

PMID- 25564088
TI  - Applications of neuromodulation to explore vestibular cortical processing; new
      insights into the effects of direct current cortical modulation upon pursuit, VOR
      and VOR suppression.
AB  - Functional imaging, lesion studies and behavioural observations suggest that
      vestibular processing is lateralised to the non-dominant hemisphere. Moreover,
      disruption of interhemispheric balance via inhibition of left parietal cortex
      using transcranial direct current stimulation (tDCS) has been associated with an
      asymmetric suppression of the vestibulo-ocular reflex (VOR). However, the
      mechanism by which the VOR was modulated remains unknown. In this paper we review
      the literature on non-invasive brain stimulation techniques which have been used
      to probe vestibular function over the last decade. In addition, we investigate
      the mechanisms whereby tDCS may modulate VOR, e.g. by acting upon pursuit, VOR
      suppression mechanisms or direct VOR modulation. We applied bi-hemispheric
      parietal tDCS in 11 healthy subjects and only observed significant effects on VOR
      gain (tdcs * condition p=0.041) - namely a trend for VOR gain increase with right
      anodal/left cathodal stimulation, and a decrease with right cathodal/left anodal
      stimulation. Hence, we suggest that the modulation of the VOR observed both here
      and in previous reports, is directly caused by top-down cortical control of the
      VOR as a result of disruption to interhemispheric balance, likely parietal. 

PMID- 25564089
TI  - Reading while moving: the functional assessment of VOR.
AB  - The head impulse test (HIT) is nowadays recognized as the gold standard for
      clinical testing of the angular vestibulo-ocular reflex (VOR). By imposing
      unpredictable, abrupt head rotations in canal pairs' planes it aims at unveiling
      the dysfunction of the semicircular canal towards which the head is rotated based
      on Ewald's II law. Functional testing of the VOR aims at assessing the ability of
      the reflex to stabilize gaze in space and thus allow clear vision during head
      movements. The HIT device (HITD) approach exploits impulsive head rotations
      spawning a range of angular accelerations while requiring subjects to identify
      optotypes briefly displayed on a screen. Here we also recorded eye movements, so
      that the evaluation of the individual subject is based both on the VOR gain and
      on the percentage of correct answers with respect to a population of controls.
      Here we used the HITD to study 14 patients suffering from vestibular neuritis and
      7 of those were re-tested after three months. We found that the HITD was able to
      unveil the ipsilesional deficit and the contralesional impairment, together with
      the improvement in the follow-up test. 

PMID- 25564090
TI  - CANVAS an update: clinical presentation, investigation and management.
AB  - BACKGROUND: Cerebellar Ataxia with Neuropathy and bilateral Vestibular Areflexia
      Syndrome (CANVAS) is a multi-system ataxia which results in cerebellar ataxia, a
      bilateral vestibulopathy and a somatosensory deficit. This sensory deficit has
      recently been shown to be a neuronopathy, with marked dorsal root ganglia
      neuronal loss. The characteristic oculomotor clinical sign is an abnormal
      visually enhanced vestibulo-ocular reflex. OBJECTIVE: To outline the expanding
      understanding of the pathology in this condition, as well as diagnostic and
      management issues encountered in clinical practice. METHODS: Retrospective data
      on 80 CANVAS patients is reviewed. RESULTS: In addition to the triad of
      cerebellar impairment, bilateral vestibulopathy and a somatosensory deficit,
      CANVAS patients may also present with orthostatic hypotension, a chronic cough
      and neuropathic pain. Management of falls risk and dysphagia is a major clinical
      priority. CONCLUSIONS: CANVAS is an increasingly recognised cause of late-onset
      ataxia and disequilibrium, and is likely to be a recessive disorder.

PMID- 25564093
TI  - The combination of the active principles of Podophyllum hexandrum supports early
      recovery of the gastrointestinal system via activation of Nrf2-HO-1 signaling and
      the hematopoietic system, leading to effective whole-body survival in lethally
      irradiated mice.
AB  - This study is aimed at the development of a safe radioprotective formulation to
      minimize human sufferings during accidental nuclear exposures. In the current
      study, a combination of three active principles, namely podophyllotoxin,
      podophyllotoxin beta-D-glucoside, and rutin (G-002M), isolated from Podophyllum
      hexandrum rhizomes, has been evaluated for its radioprotective potential and mode
      of action. Total body protection studies have demonstrated that a single
      prophylactic dose of G-002M delivered more than 85% survival in mice exposed to a
      lethal (9 Gy) dose of gamma radiation, and significantly protected the
      radiosensitive hematopoietic and gastrointestinal organs. Studies have also
      revealed a reduction in free radical generation, lipid peroxidation, protein
      carbonylation, and cell death in mouse intestine after G-002M treatment, while
      GSH was observed to be enhanced in the same tissue. Redox-sensitive transcription
      factor (Nrf2) activation and subsequent upregulation of heme oxygenase-1 (HO-1)
      and SOD-1 revealed the cytoprotective role of G-002M. A histological examination
      of the jejunum pretreated with the formulation also demonstrated less damage to
      the villi, crypts, and the mucosal layers. These observations reiterated that the
      reduction in the ROS levels, protection of cellular macromolecules, and
      activation of the antioxidant signaling pathway may have been the principle
      factors involved in G-002M- mediated protection against radiation-induced tissue
      impairment. The potentially safe and effective radioprotective characteristics of
      this new combination are encouraging for further studies for human application. 

PMID- 25564095
TI  - Thalassemia major patients using iron chelators showed a reduced plasma
      thioredoxin level and reduced thioredoxin reductase activity, despite elevated
      oxidative stress.
AB  - In the present study, we aimed to investigate plasma levels of peroxiredoxin 2
      (Prx2) and thioredoxin 1 (Trx1), and the activity of thioredoxin reductase
      (TrxR), in thalassemia major (TM) patients living in the Antalya region, Turkey.
      The patients were divided into three groups, according to chelators - the
      deferoxamine group (DFO, n = 20), the deferasirox group (DFX, n = 20), and the
      deferiprone group (DFP, n = 20), to compare any possible effect of chelators on
      antioxidative and oxidative stress parameters. A control group (n = 20) was
      selected from healthy volunteers. The activities of glutathione peroxidase (GPx),
      glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase
      (SOD), catalase (CAT), and TrxR, as well as the concentrations of Prx2, Trx1,
      glucose-6-phosphate dehydrogenase (G-6-PD), reduced glutathione (GSH), hydrogen
      peroxide (H2O2), and malondialdehyde (MDA) were measured in the plasma samples of
      TM patients and the controls. The activity of CAT and the levels of H2O2 and MDA
      in the TM patients were significantly higher than those in the controls, while
      the levels of GPx, Trx1, TrxR, and GSH were lower. The concentrations of
      ferritin, GSH, H2O2, and MDA, as well as the activities of GR, CAT and TrxR,
      showed significant differences among the chelator groups. Although TrxR activity
      showed an increase in TM patients due to an elevated iron overload, both TrxR
      activity and Trx1 level were lower in the patient groups compared with the cases
      in the control group. As a result, because Trx1 level and TrxR activity were
      measured at a low level in the patients, increasing the levels of Trx1 and TrxR
      in TM patients will be a target of future treatment. 

PMID- 25564097
TI  - Reference values of maximum walking speed among independent community-dwelling
      Danish adults aged 60 to 79 years: a cross-sectional study.
AB  - OBJECTIVES: To establish reference values for maximum walking speed over 10 m for
      independent community-dwelling Danish adults, aged 60 to 79 years, and to
      evaluate the effects of gender and age. DESIGN: Cross-sectional study. SETTING:
      Danish companies and senior citizens clubs. PARTICIPANTS: Two hundred and fifty
      two adults (167 women, 85 men) with a mean age of 70 [standard deviation (SD) 4]
      years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Results for the 10-m
      walk test (10 MWT) were used to establish reference values. RESULTS: The mean
      reference value for maximum walking speed over 10 m for all participants was 1.94
      (SD 0.31) m/second. Reference values for women aged 60 to 69 years and 70 to 79
      years were 1.96 (SD 0.26) and 1.81 (SD 0.29) m/second, respectively. Reference
      values for men aged 60 to 69 years and 70 to 79 years were 2.10 (SD 0.35) and
      2.01 (SD 0.30) m/second, respectively. Significant differences (P<0.01) were
      observed in the age and gender categories. Men were found to walk faster than
      women, and individuals aged 60 to 69 years walked faster than individuals aged 70
      to 79 years. CONCLUSIONS: This study established the reference values for maximum
      walking speed over 10 m among independent community-dwelling Danish adults aged
      60 to 79 years. The study results showed significant differences in maximum
      walking speed for different ages and between men and women.

PMID- 25564098
TI  - Henry's law constant and overall mass transfer coefficient for formaldehyde
      emission from small water pools under simulated indoor environmental conditions.
AB  - The Henry's law constant (HLC) and the overall mass transfer coefficient are both
      important parameters for modeling formaldehyde emissions from aqueous solutions.
      In this work, the apparent HLCs for formaldehyde aqueous solutions were
      determined in the concentration range from 0.01% to 1% (w/w) and at different
      temperatures (23, 40, and 55  degrees C) by a static headspace extraction method.
      The aqueous solutions tested included formaldehyde in water, formaldehyde-water
      with nonionic surfactant Tergitol NP-9, and formaldehyde-water with anionic
      surfactant sodium dodecyl sulfate. Overall, the measured HLCs ranged from 8.33 *
      10(-6) to 1.12 * 10(-4) (gas-concentration/aqueous-concentration, dimensionless).
      Fourteen small-chamber tests were conducted with formaldehyde solutions in small
      pools. By applying the measured HLCs, the formaldehyde overall liquid-phase mass
      transfer coefficients (KOLs) were determined to be in the range of 8.12 * 10(-5)
      to 2.30 * 10(-4) m/h, and the overall gas-phase mass transfer coefficients were
      between 2.84 and 13.4 m/h. The influences of the formaldehyde concentration,
      temperature, agitation rate, and surfactant on HLC and KOL were investigated.
      This study provides useful data to support source modeling for indoor
      formaldehyde originating from the use of household products that contain
      formaldehyde-releasing biocides.

PMID- 25564094
TI  - Biochemical mechanisms and therapeutic potential of pseudohalide thiocyanate in
      human health.
AB  - Thiocyanate (SCN(-)) is a ubiquitous molecule in mammalian biology, reaching up
      to mM concentrations in extracellular fluids. Two- electron oxidation of SCN(-)
      by H2O2 produces hypothiocyanous acid (HOSCN), a potent anti-microbial species.
      This reaction is catalyzed by chordate peroxidases (e.g., myeloperoxidase and
      lactoperoxidase), occurring in human secretory mucosa, including the oral cavity,
      airway, and alimentary tract, and regulates resident and transient flora as part
      of innate immunity. Increasing SCN(-) levels limits the concentrations of a
      family of 2-electron oxidants (H2O2, hypohalous acids, and haloamines) in favor
      of HOSCN formation, altering the oxidative impact on host tissue by substitution
      of repairable thiol and selenol oxidations instead of biomolecule degradation.
      This fine-tuning of inflammatory oxidation paradoxically associates with
      maintained host defense and decreased host injury during infections, due in part
      to phylogenetic differences in the thioredoxin reductase system between mammals
      and their pathogens. These differences could be exploited by pharmacologic use of
      SCN(-). Recent preclinical studies have identified anti-microbial and anti
      inflammatory effects of SCN(-) in pulmonary and cardiovascular animal models,
      with implications for treatment of infectious lung disease and atherogenesis.
      Further research is merited to expand on these findings and identify other
      diseases where SCN(-) may be of use. High oral bioavailability and an increased
      knowledge of the biochemical effects of SCN(-) on a subset of pro-inflammatory
      reactions suggest clinical utility. 

PMID- 25564099
TI  - Novel lysosome targeted molecular transporter built on a guanidinium-poly
      (propylene imine) hybrid dendron for efficient delivery of doxorubicin into
      cancer cells.
AB  - An efficient synthetic approach has been adopted to construct a new dendron-based
      octa-guanidine appended molecular transporter with a lysosomal targeted peptide
      doxorubicin conjugate. The transporter alone (G8-PPI-FL) is found to be non
      toxic, showed higher cellular uptake compared to Arg-8-mer and exhibited
      excellent selectivity towards lysosomes in cathepsin B expressing HeLa cells,
      while the Dox-conjugate showed significant cytotoxicity to cancer cells without
      affecting the non-cancerous cells. 

PMID- 25564096
TI  - Reverse zoonosis of influenza to swine: new perspectives on the human-animal
      interface.
AB  - The origins of the 2009 influenza A (H1N1) pandemic in swine are unknown,
      highlighting gaps in our understanding of influenza A virus (IAV) ecology and
      evolution. We review how recently strengthened influenza virus surveillance in
      pigs has revealed that influenza virus transmission from humans to swine is far
      more frequent than swine-to-human zoonosis, and is central in seeding swine
      globally with new viral diversity. The scale of global human-to-swine
      transmission represents the largest 'reverse zoonosis' of a pathogen documented
      to date. Overcoming the bias towards perceiving swine as sources of human
      viruses, rather than recipients, is key to understanding how the bidirectional
      nature of the human-animal interface produces influenza threats to both hosts.

PMID- 25564100
TI  - Dynamic behavior of suture-anastomosed arteries and implications to vascular
      surgery operations.
AB  - BACKGROUND: Routine vascular surgery operations involve stitching of disconnected
      human arteries with themselves or with artificial grafts (arterial anastomosis).
      This study aims to extend current knowledge and provide better-substantiated
      understanding of the mechanics of end-to-end anastomosis through the development
      of an analytical model governing the dynamic behavior of the anastomotic region
      of two initially separated arteries. METHODS: The formulation accounts for the
      arterial axial-circumferential deformation coupling and suture-artery
      interaction. The proposed model captures the effects of the most important
      parameters, including the geometric and mechanical properties of artery and
      sutures, number of sutures, loading characteristics, longitudinal residual
      stresses, and suture pre-tensioning. RESULTS: Closed-form expressions are derived
      for the system response in terms of arterial radial displacement, anastomotic
      gap, suture tensile force, and embedding stress due to suture-artery contact
      interaction. Explicit objective functionalities are established to prevent
      failure at the anastomotic interface. CONCLUSIONS: The mathematical formulation
      reveals useful interrelations among the problem parameters, thus making the
      proposed model a valuable tool for the optimal selection of materials and
      improved functionality of the sutures. By virtue of their generality and
      directness of application, the findings of this study can ultimately form the
      basis for the development of vascular anastomosis guidelines pertaining to the
      prevention of post-surgery implications.

PMID- 25564101
TI  - Injuries sustained during snow removal from roofs resulting in hospital care.
AB  - Clearing snow from roofs causes serious injuries annually. The aim of this study
      was to describe injury mechanisms, injury panorama, and injury incidence in
      connection to this activity. A specific aim was to study the association between
      snow depth and injury incidence. A total of 95 people were injured during four
      study periods. The risk of injury is strongly associated with snow depth, and the
      incidence varied up to 10-fold between the studied winter seasons. The majority
      of injuries (91; 96%) occurred during leisure time and only four people were
      injured in the occupational setting. The most common injury mechanism was falling
      off roofs or ladders of residential homes. Nearly 60% sustained moderate or
      serious injuries (Maximum Abbreviated Injury Scale [MAIS] 2-3), and fractures
      accounted for almost half of all injuries. Because roofs of single-family homes
      in Sweden usually do not require snow removal for heavy snow loads, these
      injuries may have been both unnecessary and avoidable. Further education is
      required to advise the public on the risks associated with snow removal from
      roofs. 

PMID- 25564102
TI  - spFRET reveals changes in nucleosome breathing by neighboring nucleosomes.
AB  - Chromatin, the structure in which DNA is compacted in eukaryotic cells, plays a
      key role in regulating DNA accessibility. FRET experiments on single nucleosomes,
      the basic units in chromatin, have revealed a dynamic nucleosome where
      spontaneous DNA unwrapping from the ends provides access to the nucleosomal DNA.
      Here we investigated how this DNA breathing is affected by extension of the
      linker DNA and by the presence of a neighboring nucleosome. We found that both
      electrostatic interactions between the entering and exiting linker DNA and
      nucleosome-nucleosome interactions increase unwrapping. Interactions between
      neighboring nucleosomes are more likely in dinucleosomes spaced by 55 bp of
      linker DNA than in dinucleosomes spaced by 50 bp of linker DNA. Such increased
      unwrapping may not only increase the accessibility of nucleosomal DNA in
      chromatin fibers, it may also be key to folding of nucleosomes into higher order
      structures. 

PMID- 25564103
TI  - Chlorine isotopic compositions of deep saline fluids in Ibusuki coastal
      geothermal region, Japan: using B-Cl isotopes to interpret fluid sources.
AB  - We report chlorine stable isotopic compositions (delta(37)Cl, expressed in 0/00
      relative to the standard mean ocean chloride) as well as delta(2)H and delta(18)O
      values of deep saline fluids taken at eight drill-holes reaching from 73 to 780 m
      below sea level in the Ibusuki coastal geothermal region, Japan. Analytical
      results show that the delta(37)Cl values narrowly range between -0.26 and +0.21
      0/00 with an analytical precision of +/-0.06 0/00. Except for one sample, the
      samples examined are negative in delta(37)Cl value with varying Cl/B molar ratios
      from 117 to 1265. A correlation study between the Cl/B molar ratio and the
      delta(37)Cl/delta(11)B ratio indicates a hyperbola-type mixing of at least two Cl
      sources in the Ibusuki region. One of them depletes in (37)Cl with a higher value
      of Cl/B molar ratio; and the other one enriches in (37)Cl with a lower Cl/B molar
      ratio. The former is chemically identical to that of the deep brine, which is
      altered seawater through the seawater-hot rock interaction. The latter is
      chemically similar to gas condensate derived from the high-temperature (890 
      degrees C) vent of an island-arc volcano near the Ibusuki region. 

PMID- 25564104
TI  - Sequence-based model of gap gene regulatory network.
AB  - BACKGROUND: The detailed analysis of transcriptional regulation is crucially
      important for understanding biological processes. The gap gene network in
      Drosophila attracts large interest among researches studying mechanisms of
      transcriptional regulation. It implements the most upstream regulatory layer of
      the segmentation gene network. The knowledge of molecular mechanisms involved in
      gap gene regulation is far less complete than that of genetics of the system.
      Mathematical modeling goes beyond insights gained by genetics and molecular
      approaches. It allows us to reconstruct wild-type gene expression patterns in
      silico, infer underlying regulatory mechanism and prove its sufficiency. RESULTS:
      We developed a new model that provides a dynamical description of gap gene
      regulatory systems, using detailed DNA-based information, as well as spatial
      transcription factor concentration data at varying time points. We showed that
      this model correctly reproduces gap gene expression patterns in wild type embryos
      and is able to predict gap expression patterns in Kr mutants and four reporter
      constructs. We used four-fold cross validation test and fitting to random dataset
      to validate the model and proof its sufficiency in data description. The
      identifiability analysis showed that most model parameters are well identifiable.
      We reconstructed the gap gene network topology and studied the impact of
      individual transcription factor binding sites on the model output. We measured
      this impact by calculating the site regulatory weight as a normalized difference
      between the residual sum of squares error for the set of all annotated sites and
      for the set with the site of interest excluded. CONCLUSIONS: The reconstructed
      topology of the gap gene network is in agreement with previous modeling results
      and data from literature. We showed that 1) the regulatory weights of
      transcription factor binding sites show very weak correlation with their PWM
      score; 2) sites with low regulatory weight are important for the model output; 3)
      functional important sites are not exclusively located in cis-regulatory
      elements, but are rather dispersed through regulatory region. It is of importance
      that some of the sites with high functional impact in hb, Kr and kni regulatory
      regions coincide with strong sites annotated and verified in Dnase I footprint
      assays.

PMID- 25564105
TI  - Expanding substance use treatment options for HIV prevention with buprenorphine
      naloxone: HIV Prevention Trials Network 058.
AB  - BACKGROUND: Injection opioid use plays a significant role in the transmission of
      HIV infection in many communities and several regions of the world. Access to
      evidence-based treatments for opioid use disorders is extremely limited. METHODS:
      HIV Prevention Trials Network 058 (HPTN 058) was a randomized controlled trial
      designed to compare the impact of 2 medication-assisted treatment (MAT)
      strategies on HIV incidence or death among opioid-dependent people who inject
      drugs (PWID). HIV-negative opioid-dependent PWID were recruited from 4
      communities in Thailand and China with historically high prevalence of HIV among
      PWID. A total of 1251 participants were randomly assigned to either (1) a 1-year
      intervention consisting of 2 opportunities for a 15-day detoxification with
      buprenorphine/naloxone (BUP/NX) combined with up to 21 sessions of behavioral
      drug and risk counseling [short-term medication-assisted treatment (ST-MAT)] or
      (2) thrice-weekly dosing for 48 weeks with BUP/NX and up to 21 counseling
      sessions [long-term medication-assisted treatment (LT-MAT)] followed by dose
      tapering. All participants were followed for 52 weeks after treatment completion
      to assess durability of impact. RESULTS: Although the study was stopped early due
      to lower than expected occurrence of the primary end points, sufficient data were
      available to assess the impact of the interventions on drug use and injection
      related risk behavior. At week 26, 22% of ST-MAT participants had negative
      urinalyses for opioids compared with 57% in the LT-MAT (P < 0.001). Differences
      disappeared in the year after treatment: at week 78, 35% in ST-MAT and 32% in the
      LT-MAT had negative urinalyses. Injection-related risk behaviors were
      significantly reduced in both groups after randomization. CONCLUSIONS:
      Participants receiving BUP/NX 3 times weekly were more likely to reduce opioid
      injection while on active treatment. Both treatment strategies were considered
      safe and associated with reductions in injection-related risk behavior. These
      data support the use of thrice-weekly BUP/NX as a way to reduce exposure to HIV
      risk. Continued access to BUP/NX may be required to sustain reductions in opioid
      use.

PMID- 25564106
TI  - HIV controllers with different viral load cutoff levels have distinct virologic
      and immunologic profiles.
AB  - BACKGROUND: The mechanisms behind natural control of HIV replication are still
      unclear, and several studies pointed that elite controllers (ECs) are a
      heterogeneous group. METHODS: We performed analyses of virologic, genetic, and
      immunologic parameters of HIV-1 controllers groups: (1) ECs (viral load, <80
      copies/mL); (2) ebbing elite controllers (EECs; transient viremia/blips); and
      viremic controllers (VCs; detectable viremia, <5000 copies/mL). Untreated
      noncontrollers (NCs), patients under suppressive highly active antiretroviral
      therapy (HAART), and HIV-1-negative individuals were analyzed as controls.
      RESULTS: Total and integrated HIV-1 DNA for EC were significantly lower than for
      NC and HAART groups. 2-LTR circles were detected in EEC (3/5) and VC (6/7) but
      not in EC. Although EC and EEC maintain normal T-cell counts over time, some VC
      displayed negative CD4 T-cell slopes. VC and EEC showed a higher percentage of
      activated CD8 T cells and microbial translocation than HIV-1-negative controls.
      EC displayed a weaker Gag/Nef IFN-gamma T-cell response and a significantly lower
      proportion of anti-HIV IgG antibodies than EEC, VC, and NC groups. CONCLUSION:
      Transient/persistent low-level viremia in HIV controllers may have an impact on
      immunologic and virologic profiles. Classified HIV controller patients taking
      into account their virologic profile may decrease the heterogeneity of HIV
      controllers cohorts, which may help to clarify the mechanisms associated to the
      elite control of HIV.

PMID- 25564107
TI  - Population-based surveillance of HIV drug resistance emerging on treatment and
      associated factors at sentinel antiretroviral therapy sites in Namibia.
AB  - OBJECTIVE: The World Health Organization (WHO) prospective surveys of acquired
      HIV drug resistance (HIVDR) evaluate HIVDR emerging after the first year of
      antiretroviral therapy (ART) and associated factors. METHODS: Consecutive ART
      starters in 2009 were enrolled at 3 sentinel sites in Namibia. Genotyping was
      performed at start and after 12 months in patients with HIV viral load (VL) >1000
      copies per mL. HIVDR outcomes were: HIVDR prevention (VL <=1000 copies/mL),
      possible HIVDR (VL >1000 copies/mL without detectable HIVDR or loss to follow-up
      or ART stop), and HIVDR (VL >1000 copies/mL with detectable HIVDR). Adherence was
      assessed using medication possession ratio (MPR). RESULTS: Of 394 starters, at 12
      months, 80% were on first-line ART, 1% died, 4% transferred out, 1% stopped ART,
      <1% switched to second-line, and 15% were lost to follow-up. Among patients on
      first-line, 77% had VL testing, and 94% achieved VL <=1000 copies per mL. At
      baseline, 7% had HIVDR. After 12 months, among patients with VL testing, 5% had
      HIVDR. A majority of patients failing therapy had high-level resistance to
      nonnucleoside reverse transcriptase inhibitors but none to protease inhibitors.
      All sites achieved the WHO target of >=70% HIVDR prevention. Factors associated
      with not achieving HIVDR prevention were: baseline resistance to nonnucleoside
      reverse transcriptase inhibitors [odds ratio (OR) 3.0, P = 0.023], WHO stage 3 or
      4 at baseline (OR 2.0, P = 0.012), and MPR <75% (OR 4.9, P = 0.021). CONCLUSIONS:
      Earlier ART initiation and removal of barriers to on-time drug pickups may help
      to prevent HIVDR. These data inform decisions at national and global levels on
      the effectiveness of first- and second-line regimens.

PMID- 25564108
TI  - Brief report: Endothelial colony-forming cells and inflammatory monocytes in HIV.
AB  - The relationships between HIV infection, monocyte activation, and endothelial
      colony-forming cells (ECFCs) are unknown. We compared ECFC, intermediate
      monocytes (CD14 CD16), and nonclassical monocytes (CD14 CD16) levels in HIV
      infected participants virologically suppressed on antiretroviral therapy, HIV
      infected treatment-naive participants, and HIV-uninfected healthy controls. ECFC
      levels were significantly higher in the HIV-infected virologically suppressed
      group compared with the uninfected controls. CD14 CD16 percentages (but not CD14
      CD16 cells) were significantly higher in both HIV-infected groups vs. uninfected
      controls. In the HIV-infected groups, ECFCs and CD14 CD16 intermediate monocytes
      were significantly and inversely correlated. Lower availability of ECFCs may
      partly explain the relationship between greater intermediate monocytes and
      atherosclerosis in HIV. 

PMID- 25564109
TI  - A natural biomimetic porous medium mimicking hypomineralized enamel.
AB  - OBJECTIVES: In order to evaluate the clinical impact of low viscosity resin
      infiltration in hypomineralized enamel, it is necessary to obtain a biomimetic
      porous substrate capable of mimicking enamel. The specifications for the
      biomimetic porous medium are defined using the literature data on hypomineralized
      enamel. Based on these specifications, we propose to use deproteinized dentin,
      the latter being deproteinized by heat treatment. METHODS AND RESULTS:
      Thermogravimetry analysis (TGA), field emission scanning electron microscopy
      (FESEM) observations, mercury intrusion porosimetry (MIP) tests and
      nanoindentation are performed on the deproteinized dentin tissue. Heat treatment
      is shown to be an effective and reproducible method for removing organic fluids
      and protein residues in dentin. Deproteinizing dentin also enables forming
      nanovoids by eliminating its organic matrix. The interconnected open
      nanoporosities (porosities of less than 100 nm) created at 600 degrees C are
      distributed between 14 nm and 32 nm and the total porosity is 39% (including 36%
      due to nanoporosities). At 800 degrees C, they are distributed between 60 nm and
      100 nm and total porosity is 37% (including 33% arising from the nanoporosities).
      The hydroxyapatite crystal structure is transformed less at 600 degrees C, so
      this temperature should be preferred. SIGNIFICANCE: Besides providing new
      understanding of the dentin tissue itself, this study led to characterizing a
      porous medium made of natural apatite, and proposing and validating its use as a
      porous medium mimicking hypomineralized enamel. The next logical step of this
      study is the characterization of resin infiltration in this medium and its
      mechanical reinforcement.

PMID- 25564111
TI  - Re: 'Aneurysmal degeneration of the inflow artery after arteriovenous access for
      hemodialysis'.

PMID- 25564112
TI  - Ultrasensitive detection of nucleic acids by template enhanced hybridization
      followed by rolling circle amplification and catalytic hairpin assembly.
AB  - An ultrasensitive protocol for fluorescent detection of DNA is designed by
      combining the template enhanced hybridization process (TEHP) with Rolling Circle
      Amplification (RCA) and Catalytic Hairpin Assembly (CHA), showing a remarkable
      amplification efficiency. 

PMID- 25564110
TI  - Cytotoxicity of resin composites containing bioactive glass fillers.
AB  - OBJECTIVE: To determine the in vitro cytotoxicity of dental composites containing
      bioactive glass fillers. METHODS: Dental composites (50:50 Bis-GMA/TEGDMA resin:
      72.5wt% filler, 67.5%Sr-glass and 5% OX50) containing different concentrations
      (0, 5, 10 and 15wt%) of two sol-gel bioactive glasses, BAG65 (65mole% SiO2,
      31mole% CaO, 4mole% P2O5) and BAG61 (3mole% F added) were evaluated for
      cytotoxicity using Alamar Blue assay. First, composite extracts were obtained
      from 7 day incubations of composites in cell culture medium at 37 degrees C.
      Undifferentiated pulp cells (OD-21) were exposed to dilutions of the original
      extracts for 3, 5, and 7 days. Then freshly cured composite disks were incubated
      with OD-21 cells (n=5) for 2 days. Subsequently, fresh composite disks were
      incubated in culture medium at 37 degrees C for 7 days, and then the extracted
      disks were incubated with OD-21 cells for 2 days. Finally, fresh composites disks
      were light cured for 3, 5, and 20s and incubated with OD-21 cells (n=5) for 1, 3,
      5, and 7 days. To verify that the three different curing modes produced different
      levels of degree of conversion (DC), the DC of each composite was determined by
      FTIR. Groups (n=5) were compared with ANOVA/Tukey's (alpha<=0.05). RESULTS:
      Extracts from all composites significantly reduced cell viability until a
      dilution of 1:8 or lower, where the extract became equal to the control. All
      freshly-cured composites showed significantly reduced cell viability at two days.
      However, no reduction in cell viability was observed for any composite that had
      been previously soaked in media before exposure to the cells. Composites with
      reduced DC (3s vs. 20s cure), as verified by FTIR, showed significantly reduced
      cell viability. SIGNIFICANCE: The results show that the composites, independent
      of composition, had equivalent potency in terms of reducing the viability of the
      cells in culture. Soaking the composites for 7 days before exposing them to the
      cells suggested that the "toxic" components had been extracted and the materials
      were no longer cytotoxic. The results demonstrate that the cytotoxicity of
      composites with and without BAG must predominantly be attributed to the release
      of residual monomers, and not to the presence of the BAG.

PMID- 25564113
TI  - A transcriptomic analysis for identifying the unintended effects of introducing a
      heterologous glyphosate-tolerant EPSP synthase into Escherichia coli.
AB  - Glyphosate is one of the most commonly used broad-spectrum herbicides with little
      to no hazard to animals, human beings, or the environment. Some microbial 5
      enolpyruvylshikimate-3-phosphate (EPSP) synthase variants are not inhibited by
      glyphosate, and they provide a powerful tool to engineer glyphosate-tolerant
      plants. However, the unintended effects of EPSP synthase expression patterns on
      microbes are not yet clear. Here, we use an Affymetrix GeneChip analysis to study
      how introduction of a heterologous glyphosate-tolerant EPSP synthase into a model
      microorganism Escherichia coli (E. coli) affects the global gene expression
      profile. The profile showed that 161 of 4071 genes were differentially expressed
      after the introduction of the synthase: 19 (0.47%) were up-regulated and 143
      (3.49%) were down-regulated. The microarray results, in combination with BiOLOG
      substrate utilization and amino acid composition assays, suggested that
      heterologous EPSP synthase expression had very minor effects on E. coli. Although
      a small number of genes and metabolites were affected by EPSP synthase
      expression, no functional correlations were identified among the dataset. This
      study may shed light on the effect of EPSP synthase expression on microbes, which
      should help in the assessment of environmental safety. 

PMID- 25564114
TI  - Cancer incidence among waiters: 45 years of follow-up in five Nordic countries.
AB  - AIMS: To study cancer risk patterns among waiters in the Nordic countries.
      METHODS: We identified a cohort of 16,134 male and 81,838 female waiters from
      Denmark, Finland, Iceland, Norway and Sweden. During the follow-up period from
      1961 to 2005, we found that 19,388 incident cancer cases were diagnosed.
      Standardised incidence ratio (SIR) was defined as the observed number of cancer
      cases divided by the expected number, based on national age, time period and
      gender-specific cancer incidence rates in the general population. RESULTS: The
      SIR of all cancers in waiters, in the five countries combined, was 1.46 (95% CI
      1.41-1.51) in men and 1.09 (1.07-1.11) in women. In male waiters, the SIR
      decreased from 1.79 (1.63-1.96) in 1961-1975, to 1.33 (1.26-1.40) in 1991-2005,
      but remained stable among women. The SIR among male waiters was highest for
      cancers in the pharynx (6.11; 95% CI 5.02-7.37), oral cavity (4.91; 95% CI 3.81
      6.24) and tongue (4.36; 95% CI 3.13-5.92); and in female waiters, in the larynx
      (2.17; 95% CI 1.63-2.82), oral cavity (1.96; 95% CI 1.60-2.34) and lung (1.89;
      95% CI 1.80-1.99). CONCLUSIONS: The risk of cancer among waiters was higher than
      in the general population. The elevated incidence in some cancer sites can likely
      be explained by higher alcohol consumption, the prevalence of smoking and
      occupational exposure to tobacco smoke. Hopefully, the incidence of cancer among
      waiters will decrease in the future, due to the banning of tobacco smoking in
      restaurants and bars in the Nordic countries.

PMID- 25564115
TI  - When general practitioners talk about alcohol: exploring facilitating and
      hampering factors for pragmatic case finding.
AB  - BACKGROUND: The aim was to explore individual and system factors facilitating or
      hampering pragmatic case finding, an identification strategy based on clinical
      signs and targeted screening. STUDY DESIGN: Two focus groups with general
      practitioners were interviewed twice, in the context of a four-session seminar on
      alcohol and complex drug problems, and an additional focus group interview with
      general practitioners not attending the seminar. Interviews focused mainly on
      conditions for talking about alcohol, views on collaboration with colleagues, how
      they deal with complex issues, and strategies for learning and quality
      improvement. RESULTS: The participants presented many deliberate strategies for
      quality improvement and learning together, but there was a tendency to avoid
      discussing complex case stories or potentially controversial topics with
      colleagues. Possible barriers to change were presented. The majority of their
      stories on talking about alcohol coincided well with the concept of pragmatic
      case finding. The duality between shame and normality, time constraints and a
      need for structure were the most important individual barriers to an open and
      respectful conversation about alcohol with patients. CONCLUSIONS: Our study
      supports pragmatic case finding as a relevant and viable strategy for talking
      about alcohol in general practice, and as an alternative to screening and brief
      intervention. Quality improvement in practice is strengthened when it is adapted
      to the clinical setting, and builds on and stimulates the GPS' and staff's own
      strategies for learning and quality work.

PMID- 25564116
TI  - Rising to the challenge.

PMID- 25564117
TI  - A decade of investment in infection prevention: a cost-effectiveness analysis.
AB  - BACKGROUND: Health care-associated infection (HAI) rates have fallen with the
      development of multifaceted infection prevention programs. These programs require
      ongoing investments, however. Our objective was to examine the cost-effectiveness
      of hospitals' ongoing investments in HAI prevention in intensive care units
      (ICUs). METHODS: Five years of Medicare data were combined with HAI rates and
      cost and quality of life estimates drawn from the literature. Life-years (LYs),
      quality-adjusted LYs (QALYs), and health care expenditures with and without
      central line-associated bloodstream infection (CLABSI) and/or ventilator
      associated pneumonia (VAP), as well as incremental cost-effectiveness ratios
      (ICERs) of multifaceted HAI prevention programs, were modeled. RESULTS: Total LYs
      and QALYs gained per ICU due to infection prevention programs were 15.55 LY and
      9.61 QALY for CLABSI and 10.84 LY and 6.55 QALY for VAP. Reductions in index
      admission ICU costs were $174,713.09 for CLABSI and $163,090.54 for VAP. The
      ICERs were $14,250.74 per LY gained and $23,277.86 per QALY gained. CONCLUSIONS:
      Multifaceted HAI prevention programs are cost-effective. Our results underscore
      the importance of maintaining ongoing investments in HAI prevention. The welfare
      benefits implied by the advantageous ICERs would be lost if the investments were
      suspended.

PMID- 25564118
TI  - Impact of the International Nosocomial Infection Control Consortium (INICC)
      multidimensional hand hygiene approach in 3 cities in Brazil.
AB  - BACKGROUND: Hand hygiene (HH) is the main tool for cross-infection prevention,
      but adherence to guidelines is low in limited-resource countries, and there are
      not available published data from Brazil. METHODS: This is an observational,
      prospective, interventional, before-and-after study conducted in 4 intensive care
      units in 4 hospitals, which are members of the International Nosocomial Infection
      Control Consortium (INICC), from June 2006-April 2008. The study was divided into
      a 3-month baseline period and a follow-up period. A multidimensional HH approach
      was introduced, which included administrative support, supplies availability,
      education and training, reminders in the workplace, process surveillance, and
      performance feedback. Health care workers were observed for HH practices in each
      intensive care unit during randomly selected 30-minute periods. RESULTS: We
      recorded 4,837 opportunities for HH, with an overall HH compliance that increased
      from 27%-58% (P < .01). Multivariate analysis showed that some variables were
      associated with poor HH compliance: men versus women (49% vs 38%, P < .001),
      nurses versus doctors (55% vs 48%, P < .02), among others. CONCLUSIONS: With the
      implementation of the INICC approach, adherence to HH was significantly
      increased. Programs should be aimed at improving HH in variables found to be
      predictors of poor HH compliance.

PMID- 25564119
TI  - Comparison of hand hygiene monitoring using the 5 Moments for Hand Hygiene method
      versus a wash in-wash out method.
AB  - BACKGROUND: One strategy to promote improved hand hygiene is to monitor health
      care workers' adherence to recommended practices and give feedback. For
      feasibility of monitoring, many health care facilities assess hand hygiene
      practices on room entry and exit (wash in-wash out). It is not known if the wash
      in-wash out method is comparable with a more comprehensive approach, such as the
      World Health Organization's My 5 Moments for Hand Hygiene method. METHODS: During
      a 1-month period, a surreptitious observer monitored hand hygiene compliance
      simultaneously using the wash in-wash out and My 5 Moments for Hand Hygiene
      methods. RESULTS: For 283 health care worker room entries, the methods resulted
      in similar rates of hand hygiene compliance (70% vs 72%, respectively). The wash
      in-wash out method required 148 hand hygiene events not required by the My 5
      Moments for Hand Hygiene method (ie, before and after room entry with no patient
      or environmental contact) while not providing monitoring for 89 hand hygiene
      opportunities in patient rooms. CONCLUSION: The monitoring methods resulted in
      similar overall rates of hand hygiene compliance. Use of the wash in-wash out
      method should include ongoing education and intermittent assessment of hand
      hygiene before clean procedures and after body fluid exposure in patient rooms.

PMID- 25564120
TI  - Breakthrough bacteremia in the neonatal intensive care unit: incidence, risk
      factors, and attributable mortality.
AB  - BACKGROUND: An episode of breakthrough bacteremia, which was defined as positive
      blood cultures despite appropriate antibiotic therapy, imposes a treatment
      challenge in the neonatal intensive care unit (NICU). METHODS: All episodes of
      breakthrough bacteremia from a tertiary level NICU in Taiwan between 2004 and
      2011 were analyzed and compared with nonbreakthrough bacteremia. RESULTS:
      Breakthrough bacteremia was identified in 7.6% (72/942) of neonatal bacteremia,
      and 43 (59.7%) occurred as recurrent episodes. Gram-negative organisms (41.7%)
      and fungi (15.3%) accounted for more than half of all microorganisms in
      breakthrough bacteremia. Compared with nonbreakthrough bacteremia, breakthrough
      bacteremia was significantly associated with more severe disease, was more likely
      to require aggressive therapies, and had a higher rate of infectious
      complications. Previous use of broad-spectrum antibiotics (odds ratio [OR], 7.54;
      P < .001) and particular microbial etiologies (Pseudomonas aeruginosa: OR, 4.40;
      P = .025; fungi: OR, 2.70; P = .013) were independent risk factors for developing
      breakthrough bacteremia. The crude sepsis-attributable mortality rate was greater
      in breakthrough bacteremia episodes (16.7% vs 6.4%; P = .004), and this condition
      was independently associated with an increased risk of death (OR, 2.14; 95%
      confidence interval, 1.04-4.40; P = .040). CONCLUSION: Breakthrough bacteremia is
      not uncommon (7.6% of all bacteremia) in NICUs and represents a more severe form
      of neonatal bacteremia that is independently associated with an increased risk of
      death.

PMID- 25564121
TI  - Staphylococcus aureus and the oral cavity: an overlooked source of carriage and
      infection?
AB  - BACKGROUND: The role of intraoral Staphylococcus aureus in disease and cross
      infection sources is controversial. We present a 10-year retrospective analysis
      of laboratory data reporting isolation of S aureus from oral and perioral
      clinical specimens. METHODS: A review of laboratory records for specimens where S
      aureus was isolated were collated and analyzed from January 1998-December 2007 at
      the Oral Microbiology Laboratory, Glasgow Dental Hospital. RESULTS: There were
      11,312 specimens submitted to the laboratory over the study time period. S aureus
      was isolated from 1,986 specimens (18%). Of these, 1,782 (90%) were methicillin
      sensitive S aureus (MSSA), and 204 (10%) were methicillin-resistant S aureus
      (MRSA). The most common specimen type from which MSSA was isolated was an oral
      rinse, whereas for MRSA this was a tongue swab. Most of the MRSA isolates were
      EMRSA-15 or EMRSA-16 lineage. CONCLUSION: These findings suggest that S aureus
      continues to be a frequent isolate in the oral cavity and perioral region. The
      oral cavity should be considered a source of S aureus in terms of cross-infection
      and dissemination to other body sites. The role of S aureus in the pathogenesis
      of certain oral diseases should also be considered as part of a differential
      diagnosis.

PMID- 25564122
TI  - Health care-associated methicillin-resistant Staphylococcus aureus infections
      increases the risk of postdischarge mortality.
AB  - BACKGROUND: Although many studies have estimated the impact of health care
      associated methicillin-resistant Staphylococcus aureus (MRSA) infections on
      mortality during initial hospitalization, little is known about the long-term
      risk of death in these patients. The purpose of this study was to quantify the
      effect of MRSA health care-acquired infections (HAIs) on mortality after hospital
      discharge. METHODS: Our study cohort consisted of patients with inpatient
      admission within the U.S. Department of Veterans Affairs system between October
      1, 2007, and September 30, 2010. Of these patients, we identified those with a
      positive MRSA culture from electronic microbiology reports. We constructed
      multivariable Cox proportional hazards regressions to assess the impact of a
      positive culture on postdischarge mortality in the 365 days following discharge
      using both the full cohort and a propensity score-matched subsample. RESULTS: In
      our analysis cohort of 369,743 inpatients, positive MRSA cultures were recorded
      in 3,599 (1.0%) patients. We found that positive cultures resulted in an
      increased risk of postdischarge mortality both in the full cohort (hazard ratio =
      1.42, P < .001) and in the subset of propensity score-matched patients (hazard
      ratio = 1.37, P < .0001). CONCLUSION: We found that MRSA HAIs significantly
      elevate the long-term risk of mortality. These results underscore the importance
      of infection prevention efforts in the hospital.

PMID- 25564123
TI  - Economic evaluation of appropriate duration of antibiotic prophylaxis for
      prevention of neurosurgical infections in a middle-income country.
AB  - BACKGROUND: Preoperative antibiotic prophylaxis is one of the preventive measures
      for surgical site infections (SSIs). Very little data about the cost
      effectiveness of the appropriate duration of antibiotic prophylaxis in low- and
      middle-income countries are available. We aim to assess the cost effectiveness of
      the use of antibiotic prophylaxis for <24 hours to prevent neurosurgical
      infections in a middle-income country, Turkey. METHODS: A 1-year prospective
      study was performed between June 2012 and June 2013. During this study period
      patients were followed-up on for the development of SSI by means of hospital and
      postdischarge surveillance. Patients included in the study group received
      appropriate duration of antibiotic prophylaxis (<24 hours), and the duration of
      prophylaxis was longer in the control group. The antibiotic costs per patient,
      including prophylaxis and treatment, were calculated. RESULTS: A total of 822
      operations consisting of craniotomy (n = 558), spinal fusion (n = 220), and
      ventricular shunt (n = 44) were included in the study. The study group included
      488 (59.4%) patients who underwent operations with appropriate duration (<24
      hours) of antibiotic prophylaxis. Prophylactic antibiotic cost per patient was
      significantly lower in the study group ($3.35 and $20.41, respectively). The SSI
      rates did not differ between the 2 groups: 3.5% (17/488) in the study group and
      3.6 (12/822) in the control group (P > .05). CONCLUSION: This cost-analysis study
      demonstrates that prolonged antibiotic prophylaxis correlates with increased
      burden of cost, but it is not preventive for SSI.

PMID- 25564125
TI  - A 4-year prospective study to determine the incidence and microbial etiology of
      surgical site infections at a private tertiary care hospital in Mumbai, India.
AB  - BACKGROUND: There is limited single-center data on the incidence and microbial
      etiology of surgical site infections (SSIs) from developing countries. METHODS:
      This is a prospective observational study over 4-year period (April 2009-March
      2013) at a 750-bed private multispecialty hospital in Mumbai, India, among
      patients undergoing clean and clean-contaminated surgeries. Standard guidelines
      for preventing, classifying, and diagnosing SSI were followed. RESULTS: A total
      of 24,355 patients underwent clean and clean-contaminated surgeries during the
      study period. The overall SSI rate was 1.6% (389 cases). The SSI rate in clean
      surgeries was 1.57%, and the SSI rate in clean-contaminated surgeries was 1.64%.
      Of the SSIs, 66% were caused by gram-negative bacilli (GNB) (Escherichia coli
      [22.9%], Klebsiella [18.2%], Pseudomonas [12.7%], and Acinetobacter [6.0%] were
      the top 4), 31.7% were caused by gram-positive bacilli (Staphylococcus: 70.5%,
      Enterococcus: 23.8%, Streptococcus: 1.8%), and 2.1% were caused by Candida. A
      total of 64% of the E coli and Klebsiella isolates were extended spectrum beta
      lactamase producing, 6% of the GNB were carbapenem resistant, and only 17.3% of S
      aureus isolates were methicillin resistant. CONCLUSION: Although the SSI rate is
      comparable with established international benchmarks, increasing prevalence of
      antimicrobial resistance in GNB is a matter of serious concern.

PMID- 25564124
TI  - Surgical site infection rates in 16 cities in Turkey: findings of the
      International Nosocomial Infection Control Consortium (INICC).
AB  - BACKGROUND: Surgical site infections (SSIs) are a threat to patient safety;
      however, there were no available data on SSI rates stratified by surgical
      procedure (SP) in Turkey. METHODS: Between January 2005 and December 2011, a
      cohort prospective surveillance study on SSIs was conducted by the International
      Nosocomial Infection Control Consortium (INICC) in 20 hospitals in 16 Turkish
      cities. Data from hospitalized patients were registered using the Centers for
      Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN)
      methods and definitions for SSIs. Surgical procedures (SPs) were classified into
      22 types according to International Classification of Diseases, Ninth Revision
      criteria. RESULTS: We recorded 1879 SSIs, associated with 41,563 SPs (4.3%; 95%
      confidence interval, 4.3-4.7). Among the results, the SSI rate per type of SP
      compared with rates reported by the INICC and CDC NHSN were 11.9% for ventricular
      shunt (vs 12.9% vs 5.6%); 5.3% for craniotomy (vs 4.4% vs 2.6%); 4.9% for
      coronary bypass with chest and donor incision (vs 4.5 vs 2.9); 3.5% for hip
      prosthesis (vs 2.6% vs 1.3%), and 3.0% for cesarean section (vs 0.7% vs 1.8%).
      CONCLUSIONS: In most of the 22 types of SP analyzed, our SSI rates were higher
      than the CDC NHSN rates and similar to the INICC rates. This study advances the
      knowledge of SSI epidemiology in Turkey, allowing the implementation of targeted
      interventions.

PMID- 25564126
TI  - Hospital respiratory protection practices in 6 U.S. states: a public health
      evaluation study.
AB  - BACKGROUND: Lessons learned from the influenza A (H1N1) virus revealed a need to
      better understand hospitals' respiratory protection programmatic practice gaps.
      This article reports findings from a multistate assessment of hospitals'
      adherence to the Occupational Safety and Health Administration's respiratory
      protection program (RPP) requirements and the Centers for Disease Control and
      Prevention's infection control guidance. METHODS: Onsite surveys were conducted
      in 98 acute care hospitals in 6 U.S. states, including >1,500 hospital managers,
      unit managers, and health care workers. Descriptive statistics were used to
      assess hospital adherence. RESULTS: Most acute care hospitals adhere to
      requirements for initial medical evaluations, fit testing, training, and
      recommended respiratory protection when in close contact with patients who have
      suspected or confirmed seasonal influenza. Low hospital adherence was found for
      respiratory protection with infectious diseases requiring airborne precautions,
      aerosol-generating procedures with seasonal influenza, and checking of the
      respirator's user seal. Hospitals' adherence was also low with follow-up program
      evaluations, medical re-evaluations, and respirator maintenance. CONCLUSION:
      Efforts should be made to closely examine ways of strengthening hospitals' RPPs
      to ensure the program's ongoing effectiveness and workers' proper selection and
      use of respiratory protection. Implications for improved RPPs and practice are
      discussed.

PMID- 25564127
TI  - Current practices and barriers to the use of facemasks and respirators among
      hospital-based health care workers in Vietnam.
AB  - BACKGROUND: This study aimed to examine the knowledge, attitudes, and practices
      towards the use of facemasks among hospital-based health care workers (HCWs) in
      Hanoi, Vietnam. METHODS: A qualitative study incorporating 20 focus groups was
      conducted between August 2010 and May 2011. HCWs from 7 hospitals in Vietnam were
      invited to participate. RESULTS: Issues associated with the availability of
      facemasks (medical and cloth masks) and respirators was the strongest theme to
      emerge from the discussion. Participants reported that it is not unusual for some
      types of facemasks to be unavailable during nonemergency periods. It was
      highlighted that the use of facemasks and respirators is not continuous, but
      rather is limited to selected situations, locations, and patients. Reuse of
      facemasks and respirators is also common in some settings. Finally, some
      participants reported believing that the reuse of facemasks, particularly cloth
      masks, is safe, whereas others believed that the reuse of masks put staff at risk
      of infection. CONCLUSIONS: In low and middle-income countries, access to
      appropriate levels of personal protective equipment may be restricted owing to
      competing demands for funding in hospital settings. It is important that issues
      around reuse and extended use of medical masks/respirators and decontamination of
      cloth masks are addressed in policy documents to minimize the risk of infection.

PMID- 25564128
TI  - Real-time measurements of airborne biologic particles using fluorescent particle
      counter to evaluate microbial contamination: results of a comparative study in an
      operating theater.
AB  - BACKGROUND: Airborne bacterial contamination poses a risk for surgical site
      infection, and routine surveillance of airborne bacteria is important.
      Traditional methods for detecting airborne bacteria are time consuming and
      strenuous. Measurement of biologic particle concentrations using a fluorescent
      particle counter is a novel method for evaluating air quality. The current study
      was to determine whether the number of biologic particles detected by the
      fluorescent particle counter can be used to indicate airborne bacterial counts in
      operating rooms. METHODS: The study was performed in an operating theater at a
      university hospital in Hefei, China. The number of airborne biologic particles
      every minute was quantified using a fluorescent particle counter. Microbiologic
      air sampling was performed every 30 minutes using an Andersen air sampler (Pusong
      Electronic Instruments, Changzhou, China). Correlations between the 2 different
      methods were analyzed by Pearson correlation coefficients. RESULTS: A significant
      correlation was observed between biologic particle and bacterial counts (Pearson
      correlation coefficient = 0.76), and the counting results from 2 methods both
      increased substantially between operations, corresponding with human movements in
      the operating room. CONCLUSION: Fluorescent particle counters show potential as
      important tools for monitoring bacterial contamination in operating theatres.

PMID- 25564129
TI  - Evaluation of hydrogen peroxide vapor for the inactivation of nosocomial
      pathogens on porous and nonporous surfaces.
AB  - BACKGROUND: Clostridium difficile spores and multidrug-resistant (MDR) organisms,
      such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant
      Enterococcus (VRE), and MDR Acinetobacter baumannii, are important nosocomial
      pathogens that are difficult to eliminate from the hospital environment. We
      evaluated the efficacy of hydrogen peroxide vapor (HPV), a no-touch automated
      room decontamination system, for the inactivation of a range of pathogens dried
      onto hard nonporous and porous surfaces in an operating room (OR). METHODS:
      Stainless steel and cotton carriers containing >4 log10 viable MRSA, VRE, or MDR
      A baumannii were placed at 4 locations in the OR along with 7 pouched 6
      log10Geobacillus stearothermophilus spore biologic indicators (BIs). HPV was then
      used to decontaminate the OR. The experiment was repeated 3 times. RESULTS: HPV
      inactivated all spore BIs (>6 log10 reduction), and no MRSA, VRE, or MDR A
      baumannii were recovered from the stainless steel and cotton carriers (>4-5 log10
      reduction, depending on the starting inoculum). HPV was equally effective at all
      carrier locations. We did not identify any difference in efficacy for microbes
      dried onto stainless steel or cotton surfaces, indicating that HPV may have a
      role in the decontamination of both porous and nonporous surfaces. CONCLUSION:
      HPV is an effective way to decontaminate clinical areas where contamination with
      bacterial spores and MDR organisms is suspected.

PMID- 25564130
TI  - Health care-acquired infections in neonatal intensive care units: risk factors
      and etiology.
AB  - A 1-year prospective cohort study of health care-acquired infections was
      conducted at the neonatal intensive care unit of the University Clinical Centre
      Kragujevac, Serbia. The incidence rate of neonates with health care-acquired
      infections was 18.6%, and the incidence rate of the infections themselves was
      19.4%. The incidence density of the health care-acquired infections was 9.1 per
      1,000 patient days. The independent risk factors for health care-acquired
      infections were birth weight, length of hospitalization, duration of mechanical
      ventilation, and Apgar score. More than half of all isolated microorganisms were
      Klebsiella-Enterobacter (39.3%) and Escherichia coli (25.0%). 

PMID- 25564131
TI  - Evaluation of routine pretransplantation screening for methicillin-resistant
      Staphylococcus aureus in hematopoietic cell transplant recipients.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) screening guidelines for
      hematopoietic cell transplant (HCT) recipients are not well defined.
      Retrospective assessment of standardized pretransplantation MRSA screening in a
      large single-center cohort of HCT recipients demonstrated that colonization was
      uncommon, and that no colonized patients developed posttransplantation invasive
      complications. 

PMID- 25564133
TI  - A phosphetane catalyzes deoxygenative condensation of alpha-keto esters and
      carboxylic acids via P(III)/P(V)?O redox cycling.
AB  - A small-ring phosphacycle is found to catalyze the deoxygenative condensation of
      alpha-keto esters and carboxylic acids. The reaction provides a chemoselective
      catalytic synthesis of alpha-acyloxy ester products with good functional group
      compatibility. Based on both stoichiometric and catalytic mechanistic
      experiments, the reaction is proposed to proceed via catalytic P(III)/P(V)?O
      cycling. The importance of ring strain in the phosphacyclic catalyst is
      substantiated by an observed temperature-dependent product selectivity effect.
      The results point to an inherent distinction in design criteria for
      organophosphorus-based catalysts operating via P(III)/P(V)?O redox cycling as
      opposed to Lewis base (nucleophilic) catalysis. 

PMID- 25564132
TI  - Antipsychotic prescribing in youths: a French community-based study from 2006 to
      2013.
AB  - The objectives were to explore in a community-based sample of persons aged 0-25
      years: (1) trends in antipsychotic prescribing, (2) characteristics of the zone
      of residence associated with antipsychotic prescribing rates, and (3) the pattern
      of antipsychotic prescribing. The study was performed using reimbursement data
      from the French Insurance Healthcare system. Prescribing trends were investigated
      over the period 2006-2013. An ecological design was used to assess the impact of
      the socio-economical and health resource characteristics of the zone of residence
      (n = 96 administrative subdivisions of French territory) on antipsychotic
      prescribing rates. The pattern of antipsychotic prescribing was explored in a
      cohort of youths newly treated with antipsychotics. Over the period 2006-2013,
      antipsychotic dispensing rates were stable in persons aged 0-25 years (4.8 per
      1,000 in 2006 and 4.9 per 1,000 in 2013). First-generation antipsychotic
      dispensing rates decreased from 3.1 to 2.6 per 1,000 (OR = 0.96, 95% CI 0.94
      0.98), while second-generation antipsychotic dispensing rates increased from 2.7
      to 3.4 per 1,000 (OR = 1.03, 95% CI 1.01-1.05). Antipsychotic prescribing rates
      were impacted by health resource characteristics of the zone of residence in
      children aged 10 years and under and by socio-economical characteristics in those
      aged 16-20 years. In all the age groups, antipsychotics were principally started
      by hospital practitioners (47%) and general practitioners (34%). The rates of
      psychostimulants concomitantly prescribed with antipsychotics were lower than 5%.
      In conclusion, rates of youths exposed to second-generation antipsychotics are
      still rising. The impact of environmental characteristics on antipsychotics
      prescribing and appropriateness of these prescriptions in youths should be
      further investigated.

PMID- 25564134
TI  - Abbreviating the Finger Tapping Test.
AB  - The Finger Tapping Test (FTT) has a strong empirical base but its procedures are
      inconsistent and the test can be time-consuming. To simplify and abbreviate
      administration procedures, several potential abbreviated procedures were
      evaluated using a sample of 71 individuals presenting to a VA Hospital for
      neuropsychological evaluation. A short version using the mean score of Trials 3-5
      for each hand was found to be a strong predictor of full-test performance. The
      abbreviated version also had stronger reliability than the full version, and it
      accurately predicts impairment and performance validity classification based on
      the full version. This abbreviated version appears to be more efficient and
      sufficiently accurate to be considered for use in lieu of the traditional and
      potentially longer version of the FTT. 

PMID- 25564136
TI  - Computational study of molecular structure and self-association of tri-n-butyl
      phosphates in n-dodecane.
AB  - Tri-n-butyl phosphate (TBP) is an important extractant used in the solvent
      extraction process for recovering uranium and plutonium from used nuclear fuel.
      An atomistic molecular dynamics study was used to understand the fundamental
      molecular-level behavior of extracting agents in solution. Atomistic
      parametrization was carried out using the AMBER force field to model the TBP
      molecule and n-dodecane molecule, a commonly used organic solvent. Validation of
      the optimized force field was accomplished through various thermophysical
      properties of pure TBP and pure n-dodecane in the bulk liquid phase. The mass
      density, dipole moment, self-diffusion coefficient, and heat of vaporization were
      calculated from our simulations and compared favorably with experimental values.
      The molecular structure of TBPs in n-dodecane at a dilute TBP concentration was
      examined based on radial distribution functions. 1D and 2D potential mean force
      studies were carried out to establish the criteria for identifying TBP
      aggregates. The dimerization constant of TBP in the TBP/n-dodecane mixture was
      also obtained and matched the experimental value. 

PMID- 25564137
TI  - Estimates of price and income elasticity in Greece. Greek debt crisis
      transforming cigarettes into a luxury good: an econometric approach.
AB  - OBJECTIVE: During the past decades, smoking prevalence in Greece was estimated to
      be near or over 40%. Following a sharp fall in cigarette consumption, as shown in
      current data, our objective is to assess smokers' sensitivity to cigarette price
      and consumer income changes as well as to project health benefits of an
      additional tax increase. METHODS: Cigarette consumption was considered as the
      dependent variable, with Weighted Average Price as a proxy for cigarette price,
      gross domestic product as a proxy for consumers' income and dummy variables
      reflecting smoking restrictions and antismoking campaigns. Values were computed
      to natural logarithms and regression was performed. Then, four scenarios of tax
      increase were distinguished in order to calculate potential health benefits.
      RESULTS: Short-run price elasticity is estimated at -0.441 and short-run income
      elasticity is estimated at 1.040. Antismoking campaigns were found to have a
      statistically significant impact on consumption. Results indicate that, depending
      on the level of tax increase, annual per capita consumption could fall by at
      least 209.83 cigarettes; tax revenue could rise by more than ?0.74 billion, while
      smokers could be reduced by up to 530 568 and at least 465 smoking-related deaths
      could be averted. CONCLUSIONS: Price elasticity estimates are similar to previous
      studies in Greece, while income elasticity estimates are far greater. With
      cigarettes regarded as a luxury good, a great opportunity is presented for
      decisionmakers to counter smoking. Increased taxation, along with focused
      antismoking campaigns, law reinforcement (to ensure compliance with smoking bans)
      and intensive control for smuggling could invoke a massive blow to the tobacco
      epidemic in Greece.

PMID- 25564138
TI  - Evaluating recovery following hip fracture: a qualitative interview study of what
      is important to patients.
AB  - OBJECTIVE: To explore what patients consider important when evaluating their
      recovery from hip fracture and to consider how these priorities could be used in
      the evaluation of the quality of hip fracture services. DESIGN: Semistructured
      interviews exploring the experience of recovery from hip fracture at two time
      points-4 weeks and 4 months postoperative hip fixation. Two approaches to
      analysis: thematic analysis of data specifically related to recovery from hip
      fracture; summarising the participant's experience overall. PARTICIPANTS: 31
      participants were recruited, of whom 20 were women and 12 were cognitively
      impaired. Mean age was 81.5 years. Interviews were provided by 19 patients, 14
      carers and 8 patient/carer dyad; 10 participants were interviewed twice. SETTING:
      Single major trauma centre in the West Midlands of the UK. RESULTS: Stable
      mobility (without falls or fear of falls) for valued activities was considered
      most important by participants who had some prefracture mobility and were able to
      articulate what they valued during recovery. Mobility was important for managing
      personal care, for day-to-day activities such as shopping and gardening, and for
      maintenance of mental well-being. Some participants used assistive mobility
      devices or adapted to their limitations. Others maintained their previous limited
      function through increased care provision. Many participants were unable to
      articulate what they valued as hip fracture was perceived as part of their
      decline with age. The fracture and problems from other health conditions were an
      inseparable part of one health experience. CONCLUSIONS: Prefracture mobility,
      adaptations to reduced mobility before or after fracture, and whether or not
      patients perceive themselves to be declining with age influence what patients
      consider important during recovery from hip fracture. No single patient-reported
      outcome measure could evaluate quality of care for all patients following hip
      fracture. General health-related quality of life tools may provide useful
      information within clinical trials.

PMID- 25564139
TI  - Sputum eosinophilia is a determinant of FEV1 decline in occupational asthma:
      results of an observational study.
AB  - OBJECTIVE: To evaluate the potential determinants of forced expiratory volume in
      1 s (FEV1) decline in workers with occupational asthma (OA) still exposed to the
      causative agent. We hypothesised that sputum eosinophilia might be a predictor of
      poor asthma outcome after diagnosis. SETTING, DESIGN AND PARTICIPANTS: In a
      specialistic clinical centre of the University Hospital of Pisa, we studied 39
      participants (28 M, 11 F) diagnosed as having OA, routinely followed up between
      1990 and 2009. They were a subgroup of 94 participants diagnosed as affected by
      OA in that period: 9 had been removed from work at the diagnosis, 21 were
      excluded for having ceased occupational exposure after few months from diagnosis,
      and 25 were lost at the follow-up or had no acceptable sputum measurements at the
      diagnosis. Estimates of the decline in FEV1 were obtained by means of simple
      regression analysis during the period of occupational exposure after diagnosis.
      Logistic regression was used to analyse the effects of factors (baseline FEV1 and
      sputum inflammatory cells, duration and type of exposure) that may potentially
      influence FEV1 decline. RESULTS: At follow-up (5.7+3.7 years), most participants
      were still symptomatic despite inhaled corticosteroids (ICS) treatment and had
      their occupational exposure reduced. Participants with higher sputum eosinophils
      (>3%) at baseline had a significantly greater decline of FEV1 (-52.5 vs -18.6
      mL/year, p=0.012). Logistic regression showed that persistent exposure and sputum
      eosinophilia were significantly associated with a greater decline in FEV1 (OR
      11.5, 95% CI 1.8 to 71.4, p=0.009 and OR 6.7, 95% CI 1.1 to 41.7, p= 0.042,
      respectively). CONCLUSIONS: Sputum eosinophilia at diagnosis, together with the
      persistence of occupational exposure during follow-up, may contribute to a
      greater decline in FEV1 in patients with OA still at work. Further long-term
      studies are required as to whether intensive ICS treatment may be beneficial for
      patients with OA and increase ad eosinophilic inflammation.

PMID- 25564140
TI  - Low health literacy and cancer screening among Chinese Americans in California: a
      cross-sectional analysis.
AB  - OBJECTIVES: Cancer is the leading cause of death among Asian Americans. Chinese
      Americans comprise the largest Asian American ethnic group. Low health literacy
      (LHL) is associated with lower cancer screening rates, but this association has
      not been studied in Chinese Americans. We examined the relationship between LHL
      and meeting US Preventive Service Task Force (USPSTF) guidelines for cervical,
      colorectal and breast cancer screening among Chinese Americans. DESIGN:
      Observational study of Chinese respondents in the 2007 California Health
      Interview Survey, a population-based survey. Interview languages included
      English, Cantonese and Mandarin. SETTING: California, USA PARTICIPANTS: Chinese
      respondents in age/gender groupings appropriate for USPSTF cancer screening
      guidelines (cervical: women ages 21-65, n=632; colorectal: men or women ages 50
      75, n=488; and breast: women ages 50-74, n=326). OUTCOMES: Relationships were
      tested using multivariable logistic regression models controlling for healthcare
      access and demographic factors, including limited English proficiency (LEP). The
      combined effects of having both LHL and LEP were specifically examined. LHL was
      measured by 2-items on perceived ease-of-use of written medical materials. All
      study variables were self-reported. RESULTS: Cancer screening percentages among
      Chinese Americans were 77.8% for cervical, 50.9% for colorectal (47.9% for women
      and 54.2% for men), and 85.5% for breast. LHL was associated with lower odds of
      meeting breast cancer screening guidelines (OR 0.41; 95% CI 0.20 to 0.82).
      Respondents with both LHL and LEP were significantly less likely to have up-to
      date colorectal (OR 0.49; 95% CI 0.25 to 0.97) and breast cancer screening (OR
      0.21; 95% CI 0.08 to 0.54) than those with neither health communication barrier.
      In all multivariable models, having seen a physician in the past year was a
      significant predictor of an up-to-date screening. CONCLUSIONS: In Chinese
      Americans, LHL and LEP were negatively associated with up-to-date breast and
      colorectal cancer screening, independent of a recent physician visit. Efforts to
      promote cancer screening among Chinese Americans should consider and address LHL,
      LEP and physician access barriers.

PMID- 25564141
TI  - Prevalence of c.2268dup and detection of two novel alterations, c.670_672del and
      c.1186C>T, in the TPO gene in a cohort of Malaysian-Chinese with thyroid
      dyshormonogenesis.
AB  - OBJECTIVES: The c.2268dup mutation in the thyroid peroxidase (TPO) gene is the
      most common TPO alteration reported in Taiwanese patients with thyroid
      dyshormonogenesis. The ancestors of these patients are believed to originate from
      the southern province of China. Our previous study showed that this mutation
      leads to reduced abundance of the TPO protein and loss of TPO enzyme activity in
      a Malaysian-Chinese family with goitrous hypothyroidism. The aim of our study was
      to provide further data on the incidence of the c.2268dup mutation in a cohort of
      Malaysian-Chinese and its possible phenotypic effects. SETTING: Cohort study.
      PARTICIPANTS: Twelve biologically unrelated Malaysian-Chinese patients with
      congenital hypothyroidism were recruited in this study. All patients showed high
      thyrotropin and low free thyroxine levels at the time of diagnosis with proven
      presence of a thyroid gland. PRIMARY OUTCOME MEASURE: Screening of the c.2268dup
      mutation in the TPO gene in all patients was carried out using a PCR-direct DNA
      sequencing method. SECONDARY OUTCOME MEASURE: Further screening for mutations in
      other exonic regions of the TPO gene was carried out if the patient was a carrier
      of the c.2268dup mutation. RESULTS: The c.2268dup mutation was detected in 4 of
      the 12 patients. Apart from the c.2268dup and a previously documented mutation
      (c.2647C>T), two novel TPO alterations, c.670_672del and c.1186C>T, were also
      detected in our patients. In silico analyses predicted that the novel alterations
      affect the structure/function of the TPO protein. CONCLUSIONS: The c.2268dup
      mutation was detected in approximately one-third of the Malaysian-Chinese
      patients with thyroid dyshormonogenesis. The detection of the novel c.670_672del
      and c.1186C>T alterations expand the mutation spectrum of TPO associated with
      thyroid dyshormonogenesis.

PMID- 25564142
TI  - Healthcare professionals' perceptions of clinical governance implementation: a
      qualitative New Zealand study of 3205 open-ended survey comments.
AB  - OBJECTIVES: To investigate healthcare professional perceptions of local
      implementation of a national clinical governance policy in New Zealand. DESIGN:
      Respondent comments written at the end of a national healthcare professional
      survey designed to assess implementation of core components of the clinical
      governance policy. SETTING: The written comments were provided by respondents to
      a survey distributed to over 41 000 registered healthcare professionals employed
      in 19 of New Zealand's government-funded District Health Boards. Comments were
      analysed and categorised within emerging themes. RESULTS: 3205 written comments
      were received. Five key themes illustrating barriers to clinical governance
      implementation were found, representing problems with: developing management
      clinical relations; clinicians stepping up into clinical governance and
      leadership activities; interprofessional relations; training needs for governance
      and leadership; and having insufficient time to get involved. CONCLUSIONS:
      Despite a national policy on clinical governance which New Zealand's government
      launched in 2009, this study found that considerable effort is required to build
      clinical governance at the local level. This finding parallels with other studies
      in the field. Two areas demand attention: building systems for organisational
      governance and leadership; and building professional governance arrangements.

PMID- 25564143
TI  - The effect of simvastatin on inflammatory cytokines in community-acquired
      pneumonia: a randomised, double-blind, placebo-controlled trial.
AB  - OBJECTIVES: It has been suggested that statins have an effect on the modulation
      of the cytokine cascade and on the outcome of patients with community-acquired
      pneumonia (CAP). The aim of this prospective, randomised, double-blind, placebo
      controlled trial was to determine whether statin therapy given to hospitalised
      patients with CAP improves clinical outcomes and reduces the concentration of
      inflammatory cytokines. SETTING: A tertiary teaching hospital in Barcelona,
      Spain. PARTICIPANTS: Thirty-four patients were randomly assigned and included in
      an intention-to-treat analysis (19 to the simvastatin group and 15 to the placebo
      group). INTERVENTION: Patients were randomly assigned to receive 20 mg of
      simvastatin or placebo administered in the first 24 h of hospital admission and
      once daily thereafter for 4 days. OUTCOME: Primary end point was the time from
      hospital admission to clinical stability. The secondary end points were serum
      concentrations of inflammatory cytokines and partial pressure of arterial
      oxygen/fractional inspired oxygen (PaO2/FiO2) at 48 h after treatment
      administration. RESULTS: The trial was stopped because enrolment was much slower
      than originally anticipated. The baseline characteristics of the patients and
      cytokine concentrations at the time of enrolment were similar in the two groups.
      No significant differences in the time from hospital admission to clinical
      stability were found between study groups (median 3 days, IQR 2-5 vs 3 days, IQR
      2-5; p=0.47). No significant differences in PaO2/FiO2 (p=0.37), C reactive
      protein (p=0.23), tumour necrosis factor-alpha (p=0.58), interleukin 6 (IL-6;
      p=0.64), and IL-10 (p=0.61) levels at 48 h of hospitalisation were found between
      simvastatin and placebo groups. Similarly, transaminase and total creatine kinase
      levels were similar between study groups at 48 h of hospitalisation (p=0.19, 0.08
      and 0.53, respectively). CONCLUSIONS: Our results suggest that the use of
      simvastatin, 20 mg once daily for 4 days, since hospital admission did not reduce
      the time to clinical stability and the levels of inflammatory cytokines in
      hospitalised patients with CAP. TRIAL REGISTRATION NUMBER: ISRCTN91327214.

PMID- 25564144
TI  - Long-term prognosis after acute kidney injury (AKI): what is the role of baseline
      kidney function and recovery? A systematic review.
AB  - OBJECTIVES: To summarise the evidence from studies of acute kidney injury (AKI)
      with regard to the effect of pre-AKI renal function and post-AKI renal function
      recovery on long-term mortality and renal outcomes, and to assess whether these
      factors should be taken into account in future prognostic studies.
      DESIGN/SETTING: A systematic review of observational studies listed in Medline
      and EMBASE from 1990 to October 2012. PARTICIPANTS: All AKI studies in adults
      with data on baseline kidney function to identify AKI; with outcomes either
      stratified by pre-AKI and/or post-AKI kidney function, or described by the timing
      of the outcomes. OUTCOMES: Long-term mortality and worsening chronic kidney
      disease (CKD). RESULTS: Of 7385 citations, few studies met inclusion criteria,
      reported baseline kidney function and stratified by pre-AKI or post-AKI function.
      For mortality outcomes, three studies compared patients by pre-AKI renal function
      and six by post-AKI function. For CKD outcomes, two studies compared patients by
      pre-AKI function and two by post-AKI function. The presence of CKD pre-AKI
      (compared with AKI alone) was associated with doubling of mortality and a
      fourfold to fivefold increase in CKD outcomes. Non-recovery of kidney function
      was associated with greater mortality and CKD outcomes in some studies, but
      findings were inconsistent varying with study design. Two studies also reported
      that risk of poor outcome reduced over time post-AKI. Meta-analysis was precluded
      by variations in definitions for AKI, CKD and recovery. CONCLUSIONS: The long
      term prognosis after AKI varies depending on cause and clinical setting, but it
      may also, in part, be explained by underlying pre-AKI and post-AKI renal function
      rather than the AKI episode itself. While carefully considered in clinical
      practice, few studies address these factors and with inconsistent study design.
      Future AKI studies should report pre-AKI and post-AKI function consistently as
      additional factors that may modify AKI prognosis.

PMID- 25564145
TI  - Systematic review of mental health and well-being outcomes following community
      based obesity prevention interventions among adolescents.
AB  - OBJECTIVES: This paper aimed to systematically evaluate the mental health and
      well-being outcomes observed in previous community-based obesity prevention
      interventions in adolescent populations. SETTING: Systematic review of literature
      from database inception to October 2014. Articles were sourced from CINAHL,
      Global Health, Health Source: Nursing and Academic Edition, MEDLINE, PsycARTICLES
      and PsycINFO, all of which were accessed through EBSCOhost. The Cochrane Database
      was also searched to identify all eligible articles. PRISMA guidelines were
      followed and search terms and search strategy ensured all possible studies were
      identified for review. PARTICIPANTS: Intervention studies were eligible for
      inclusion if they were: focused on overweight or obesity prevention, community
      based, targeted adolescents (aged 10-19 years), reported a mental health or well
      being measure, and included a comparison or control group. Studies that focused
      on specific adolescent groups or were treatment interventions were excluded from
      review. Quality of evidence was assessed using the Grading of Recommendations,
      Assessment, Development and Evaluation (GRADE) guidelines. PRIMARY AND SECONDARY
      OUTCOME MEASURES: Primary outcomes were measures of mental health and well-being,
      including diagnostic and symptomatic measures. Secondary outcomes included
      adiposity or weight-related measures. RESULTS: Seven studies met the inclusion
      criteria; one reported anxiety/depressive outcomes, two reported on self
      perception well-being measures such as self-esteem and self-efficacy, and four
      studies reported outcomes of quality of life. Positive mental health outcomes
      demonstrated that following obesity prevention, interventions included a decrease
      in anxiety and improved health-related quality of life. Quality of evidence was
      graded as very low. CONCLUSIONS: Although positive outcomes for mental health and
      well-being do exist, controlled evaluations of community-based obesity prevention
      interventions have not often included mental health measures (n=7). It is
      recommended that future interventions incorporate mental health and well-being
      measures to identify any potential mechanisms influencing adolescent weight
      related outcomes, and equally to ensure interventions are not causing harm to
      adolescent mental health.

PMID- 25564146
TI  - Primary bacteraemia is associated with a higher mortality risk compared with
      pulmonary and intra-abdominal infections in patients with sepsis: a prospective
      observational cohort study.
AB  - OBJECTIVE: To investigate whether common infection foci (pulmonary, intra
      abdominal and primary bacteraemia) are associated with variations in mortality
      risk in patients with sepsis. DESIGN: Prospective, observational cohort study.
      SETTING: Three surgical intensive care units (ICUs) at a university medical
      centre. PARTICIPANTS: A total of 327 adult Caucasian patients with sepsis
      originating from pulmonary, intra-abdominal and primary bacteraemia participated
      in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: The patients were followed
      for 90 days and mortality risk was recorded as the primary outcome variable. To
      monitor organ failure, sepsis-related organ failure assessment (Sequential Organ
      Failure Assessment, SOFA) scores were evaluated at the onset of sepsis and
      throughout the observational period as secondary outcome variables. RESULTS: A
      total of 327 critically ill patients with sepsis were enrolled in this study.
      Kaplan-Meier survival analysis showed that the 90-day mortality risk was
      significantly higher among patients with primary bacteraemia than among those
      with pulmonary and intra-abdominal foci (58%, 35% and 32%, respectively;
      p=0.0208). To exclude the effects of several baseline variables, we performed
      multivariate Cox regression analysis. Primary bacteraemia remained a significant
      covariate for mortality in the multivariate analysis (HR 2.10; 95% CI 1.14 to
      3.86; p=0.0166). During their stay in the ICU, the patients with primary
      bacteraemia presented significantly higher SOFA scores than those of the patients
      with pulmonary and intra-abdominal infection foci (8.5+/-4.7, 7.3+/-3.4 and 5.8+/
      3.5, respectively). Patients with primary bacteraemia presented higher SOFA-renal
      score compared with the patients with other infection foci (1.6+/-1.4, 0.8+/-1.1
      and 0.7+/-1.0, respectively); the patients with primary bacteraemia required
      significantly more renal replacement therapy than the patients in the other
      groups (29%, 11% and 12%, respectively). CONCLUSIONS: These results indicate that
      patients with sepsis with primary bacteraemia present a higher mortality risk
      compared with patients with sepsis of pulmonary or intra-abdominal origins. These
      results should be assessed in patients with sepsis in larger, independent
      cohorts.

PMID- 25564147
TI  - Prevalence of tinnitus and/or hyperacusis in children and adolescents: study
      protocol for a systematic review.
AB  - INTRODUCTION: There is some debate as to what extent epidemiological data for the
      prevalence of childhood tinnitus can be relied on. While indications are that the
      prevalence is relatively high, referral numbers for children with tinnitus are
      reported to be low and many of the studies have a number of methodological
      difficulties. We describe the protocol of a systematic review aimed at assessing
      the prevalence of tinnitus and/or hyperacusis in children and young people.
      METHODS AND ANALYSIS: We will include studies of any design (except case reports
      or case series) comparing the prevalence of tinnitus and/or hyperacusis in
      children and young people with and without hearing loss, any known external
      exposure and psychological disorders. We will search the following databases:
      PubMed, EMBASE and Scopus. No restrictions of language will be applied in the
      search strategy but during the article selection language is limited to English,
      German and Scandinavian languages. Primary and additional outcomes will be the
      prevalence of tinnitus/hyperacusis and the severity, respectively. ETHICS AND
      DISSEMINATION: No ethical issues are foreseen. The results will be published in a
      peer-reviewed journal and presented at national and international conferences of
      audiology and paediatrics. TRAIL REGISTRATION NUMBER: This review protocol is
      registered in the PROSPERO International Prospective Register of Systematic
      Reviews, registration number CRD42014013456.

PMID- 25564149
TI  - Perception and use of massive open online courses among medical students in a
      developing country: multicentre cross-sectional study.
AB  - OBJECTIVES: To assess the prevalence of awareness and use of massive open online
      courses (MOOCs) among medical undergraduates in Egypt as a developing country, as
      well as identifying the limitations and satisfaction of using these courses.
      DESIGN: A multicentre, cross-sectional study using a web-based, pilot-tested and
      self-administered questionnaire. SETTINGS: Ten out of 19 randomly selected
      medical schools in Egypt. PARTICIPANTS: 2700 undergraduate medical students were
      randomly selected, with an equal allocation of participants in each university
      and each study year. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome
      measures were the percentages of students who knew about MOOCs, students who
      enrolled and students who obtained a certificate. Secondary outcome measures
      included the limitations and satisfaction of using MOOCs through five-point
      Likert scale questions. RESULTS: Of 2527 eligible students, 2106 completed the
      questionnaire (response rate 83.3%). Of these students, 456 (21.7%) knew the term
      MOOCs or websites providing these courses. Out of the latter, 136 (29.8%)
      students had enrolled in at least one course, but only 25 (18.4%) had completed
      courses earning certificates. Clinical year students showed significantly higher
      rates of knowledge (p=0.009) and enrolment (p<0.001) than academic year students.
      The primary reasons for the failure of completion of courses included lack of
      time (105; 77.2%) and slow Internet speed (73; 53.7%). Regarding the 25 students
      who completed courses, 21 (84%) were satisfied with the overall experience.
      However, there was less satisfaction regarding student-instructor (8; 32%) and
      student-student (5; 20%) interactions. CONCLUSIONS: About one-fifth of Egyptian
      medical undergraduates have heard about MOOCs with only about 6.5% actively
      enrolled in courses. Students who actively participated showed a positive
      attitude towards the experience, but better time-management skills and faster
      Internet connection speeds are required. Further studies are needed to survey the
      enrolled students for a better understanding of their experience.

PMID- 25564148
TI  - Severity of urban cycling injuries and the relationship with personal, trip,
      route and crash characteristics: analyses using four severity metrics.
AB  - OBJECTIVE: To examine the relationship between cycling injury severity and
      personal, trip, route and crash characteristics. METHODS: Data from a previous
      study of injury risk, conducted in Toronto and Vancouver, Canada, were used to
      classify injury severity using four metrics: (1) did not continue trip by bike;
      (2) transported to hospital by ambulance; (3) admitted to hospital; and (4)
      Canadian Triage and Acuity Scale (CTAS). Multiple logistic regression was used to
      examine associations with personal, trip, route and crash characteristics.
      RESULTS: Of 683 adults injured while cycling, 528 did not continue their trip by
      bike, 251 were transported by ambulance and 60 were admitted to hospital for
      further treatment. Treatment urgencies included 75 as CTAS=1 or 2 (most medically
      urgent), 284 as CTAS=3, and 320 as CTAS=4 or 5 (least medically urgent). Older
      age and collision with a motor vehicle were consistently associated with
      increased severity in all four metrics and statistically significant in three
      each (both variables with ambulance transport and CTAS; age with hospital
      admission; and motor vehicle collision with did not continue by bike). Other
      factors were consistently associated with more severe injuries, but statistically
      significant in one metric each: downhill grades; higher motor vehicle speeds;
      sidewalks (these significant for ambulance transport); multiuse paths and local
      streets (both significant for hospital admission). CONCLUSIONS: In two of
      Canada's largest cities, about one-third of the bicycle crashes were collisions
      with motor vehicles and the resulting injuries were more severe than in other
      crash circumstances, underscoring the importance of separating cyclists from
      motor vehicle traffic. Our results also suggest that bicycling injury severity
      and injury risk would be reduced on facilities that minimise slopes, have lower
      vehicle speeds, and that are designed for bicycling rather than shared with
      pedestrians.

PMID- 25564150
TI  - Real-time patterns of smoking and alcohol use: an observational study protocol of
      risky-drinking smokers.
AB  - INTRODUCTION: Despite the strong relationship between smoking and health-related
      consequences, very few smokers quit. Heavy drinking is a significant risk factor
      for health consequences, and is implicated in persistent smoking and less success
      at quitting smoking. Self-efficacy (SE) to abstain from smoking is an important
      determinant of smoking outcomes and may link alcohol use to poor quit rates. Even
      though research has demonstrated a strong association between drinking and
      smoking, and the multiplicative effect of these substances on cancer-related,
      heavy-drinking smokers has been largely ignored in the literature. Further,
      research has not taken advantage of innovative methods, such as ecological
      momentary assessment, to capture the impact of daily factors on smoking cessation
      outcomes in this particular group. The proposed study identifies daily changing
      factors that impede or promote SE and future smoking cessation efforts in risky
      drinking smokers. METHODS AND ANALYSIS: This is an observational study of 84
      regular smokers (>=10 cigarettes per day) who drink at risky levels, report a
      desire to quit in the next 6 months, and show no evidence of psychiatric
      disturbance, severe history of alcohol withdrawal or drug dependence (excluding
      nicotine and caffeine). Participants report on their smoking, alcohol consumption
      and SE related to smoking twice a day for 28 days using interactive voice
      response (IVR) surveys. Multilevel regression and path models will examine within
      person daily associations among drinking, smoking and SE, and how these variables
      predict the likelihood of future smoking behaviour at 1 and 6 months follow-up.
      ETHICS AND DISSEMINATION: This protocol was approved by an accredited
      Institutional Review Board. The findings will help us understand the factors that
      promote or impede smoking cessation among a high-risk group of smokers (heavy
      drinking smokers) and will be disseminated through peer-reviewed journal articles
      and presentations at national conferences.

PMID- 25564153
TI  - Ceritinib for the treatment of late-stage (metastatic) non-small cell lung
      cancer.
AB  - Over the past decade, the non-small cell lung cancer therapeutics landscape has
      been dominated by the increasing focus on identification and validation of
      molecular targets, as well as the identification of the best candidate agents to
      address these targets. Among the notable successes have been the approval of
      erlotinib, gefitinib, and afatinib for the EGFR mutation, and more recently
      crizotinib for anaplastic lymphoma kinase (ALK) gene rearrangement. Despite the
      excellent efficacy of crizotinib, several mechanisms of resistance, including
      secondary mutation in the ALK gene, eventually result in disease progression, and
      several second-generation ALK inhibitors, notably ceritinib, have demonstrated
      evidence of clinical activity in this setting. This review discusses the data
      associated with the recent accelerated approval of ceritinib for treatment of
      patients with ALK-positive, metastatic lung adenocarcinoma with disease
      progression on or who are intolerant to crizotinib.

PMID- 25564151
TI  - Protocol of a thyroid cancer longitudinal study (T-CALOS): a prospective,
      clinical and epidemiological study in Korea.
AB  - INTRODUCTION: Thyroid cancer incidence in Korea is the highest in the world and
      has recently increased steeply. However, factors contributing to this sudden
      increase have not been fully elucidated, and few studies have explored the
      postoperative prognosis. The Thyroid Cancer Longitudinal Study (T-CALOS) was
      initiated with three aims: (1) to identify factors predicting quality of life,
      recurrence, and incidence of other diseases after thyroid cancer treatments; (2)
      to investigate environmental exposure to radiation, toxicants and molecular
      factors in relation to tumour aggressiveness; and (3) to evaluate gene
      environment interactions that increase thyroid cancer in comparison with healthy
      participants from a pool of nationwide population-based healthy examinees.
      METHODS AND ANALYSIS: T-CALOS enrols patients with incident thyroid cancer from
      three general hospitals, Seoul National University Hospital, Seoul National
      University Bundang Hospital and National Medical Center, Korea. The study is an
      ongoing project expecting to investigate 5000 patients with thyroid cancer up
      until 2017. Healthy examinees with a normal thyroid confirmed by sonography have
      been enrolled at the Healthy Examination Center at Seoul National University
      Hospital. We are also performing individual matching using two nationwide
      databases that are open to the public. Follow-up information is obtained at
      patients' clinical visits and by linkage to the national database. For
      statistical analysis, we will use conditional logistic regression models and a
      Cox proportional hazard regression model. A number of stratifications and
      sensitivity analyses will be performed to confirm the results. ETHICS AND
      DISSEMINATION: Based on a large sample size, a prospective study design,
      comprehensive data collection and biobank, T-CALOS has been independently peer
      reviewed and approved by the three hospitals and two funding sources (National
      Research Foundation of Korea and Korean Foundation for Cancer Research). The
      results of T-CALOS will be published according to the Strengthening the Reporting
      of Observational Studies in Epidemiology (STROBE) criteria.

PMID- 25564152
TI  - PEST domain mutations in Notch receptors comprise an oncogenic driver segment in
      triple-negative breast cancer sensitive to a gamma-secretase inhibitor.
AB  - PURPOSE: To identify and characterize novel, activating mutations in Notch
      receptors in breast cancer and to determine response to the gamma secretase
      inhibitor (GSI) PF-03084014. EXPERIMENTAL DESIGN: We used several computational
      approaches, including novel algorithms, to analyze next-generation sequencing
      data and related omic datasets from The Cancer Genome Atlas (TCGA) breast cancer
      cohort. Patient-derived xenograft (PDX) models were sequenced, and Notch-mutant
      models were treated with PF-03084014. Gene-expression and functional analyses
      were performed to study the mechanism of activation through mutation and
      inhibition by PF-03084014. RESULTS: We identified mutations within and upstream
      of the PEST domains of NOTCH1, NOTCH2, and NOTCH3 in the TCGA dataset. Mutations
      occurred via several genetic mechanisms and compromised the function of the PEST
      domain, a negative regulatory domain commonly mutated in other cancers. Focal
      amplifications of NOTCH2 and NOTCH3 were also observed, as were
      heterodimerization or extracellular domain mutations at lower incidence.
      Mutations and amplifications often activated the Notch pathway as evidenced by
      increased expression of canonical Notch target genes, and functional mutations
      were significantly enriched in the triple-negative breast cancer subtype (TNBC).
      PDX models were also identified that harbored PEST domain mutations, and these
      models were highly sensitive to PF-03084014. CONCLUSIONS: This work suggests that
      Notch-altered breast cancer constitutes a bona fide oncogenic driver segment with
      the most common alteration being PEST domain mutations present in multiple Notch
      receptors. Importantly, functional studies suggest that this newly identified
      class can be targeted with Notch inhibitors, including GSIs.

PMID- 25564154
TI  - Actin-curcumin interaction: insights into the mechanism of actin polymerization
      inhibition.
AB  - Curcumin, derived from rhizomes of the Curcuma longa plant, is known to possess a
      wide range of medicinal properties. We have examined the interaction of curcumin
      with actin and determined their binding and thermodynamic parameters using
      isothermal titration calorimetry. Curcumin is weakly fluorescent in aqueous
      solution, and binding to actin enhances fluorescence several fold with a large
      blue shift in the emission maximum. Curcumin inhibits microfilament formation,
      which is similar to its role in inhibiting microtubule formation. We synthesized
      a series of stable curcumin analogues to examine their affinity for actin and
      their ability to inhibit actin self-assembly. Results show that curcumin is a
      ligand with two symmetrical halves, each of which possesses no activity
      individually. Oxazole, pyrazole, and acetyl derivatives are less effective than
      curcumin at inhibiting actin self-assembly, whereas a benzylidiene derivative is
      more effective. Cell biology studies suggest that disorganization of the actin
      network leads to destabilization of filaments in the presence of curcumin.
      Molecular docking reveals that curcumin binds close to the cytochalasin binding
      site of actin. Further molecular dynamics studies reveal a possible allosteric
      effect in which curcumin binding at the "barbed end" of actin is transmitted to
      the "pointed end", where conformational changes disrupt interactions with the
      adjacent actin monomer to interrupt filament formation. Finally, the recognition
      and binding of actin by curcumin is yet another example of its unique ability to
      target multiple receptors. 

PMID- 25564155
TI  - Nucleosome positioning and composition modulate in silico chromatin flexibility.
AB  - The dynamic organization of chromatin plays an essential role in the regulation
      of gene expression and in other fundamental cellular processes. The underlying
      physical basis of these activities lies in the sequential positioning, chemical
      composition, and intermolecular interactions of the nucleosomes-the familiar
      assemblies of ~150 DNA base pairs and eight histone proteins-found on chromatin
      fibers. Here we introduce a mesoscale model of short nucleosomal arrays and a
      computational framework that make it possible to incorporate detailed structural
      features of DNA and histones in simulations of short chromatin constructs. We
      explore the effects of nucleosome positioning and the presence or absence of
      cationic N-terminal histone tails on the 'local' inter-nucleosomal interactions
      and the global deformations of the simulated chains. The correspondence between
      the predicted and observed effects of nucleosome composition and numbers on the
      long-range communication between the ends of designed nucleosome arrays lends
      credence to the model and to the molecular insights gleaned from the simulated
      structures. We also extract effective nucleosome-nucleosome potentials from the
      simulations and implement the potentials in a larger-scale computational
      treatment of regularly repeating chromatin fibers. Our results reveal a
      remarkable effect of nucleosome spacing on chromatin flexibility, with small
      changes in DNA linker length significantly altering the interactions of
      nucleosomes and the dimensions of the fiber as a whole. In addition, we find that
      these changes in nucleosome positioning influence the statistical properties of
      long chromatin constructs. That is, simulated chromatin fibers with the same
      number of nucleosomes exhibit polymeric behaviors ranging from Gaussian to worm
      like, depending upon nucleosome spacing. These findings suggest that the physical
      and mechanical properties of chromatin can span a wide range of behaviors,
      depending on nucleosome positioning, and that care must be taken in the choice of
      models used to interpret the experimental properties of long chromatin fibers. 

PMID- 25564156
TI  - Safety, efficacy, and long-term follow-up evaluation of perioperative epirubicin,
      Cisplatin, and capecitabine chemotherapy in esophageal resection for
      adenocarcinoma.
AB  - BACKGROUND: Perioperative epirubicin, cisplatin, and capecitabine (ECC)
      chemotherapy was evaluated in patients who underwent esophageal resection for
      adenocarcinoma of the esophagus or gastroesophageal junction (GEJ). METHODS: A
      cohort of 93 consecutive patients was analyzed. The median follow-up period was
      60 months. Source data verification of adverse events was performed by two
      independent observers. RESULTS: All three planned preoperative chemotherapy
      cycles were administered to 65 patients (69.9 %). Only 27 % of the patients
      completed both pre- and postoperative chemotherapy. The reasons for not receiving
      postoperative adjuvant chemotherapy could be separated in two main problems:
      toxicity of the preoperative chemotherapy and postoperative problems involving
      difficulty in recovery and postoperative complications. Finally, 25 patients (27
      %), completed three preoperative and three postoperative cycles. Grades 3 and 4
      nonhematologic adverse events of preoperative chemotherapy mainly consisted of
      thromboembolic events (16.2 %) and cardiac complications (7.5 %). A history of
      cardiac and vascular disease was independently associated with discontinuation of
      preoperative chemotherapy and the occurrence of grade 3 or higher adverse events.
      Surgery was performed for 94 % of all the patients who started with ECC
      chemotherapy. A radical resection (R0) was achieved in 93 % of the patients. A
      complete pathologic response was observed in 8 % of the patients. During a median
      follow-up period of 60 months, the median disease-free survival time was 28
      months, and the median overall survival time was 36 months. The 3-year overall
      survival rate was 50 %, and the 5-year overall survival rate was 42 %.
      CONCLUSION: For patients with adenocarcinoma of the esophagus or GEJ, six cycles
      of ECC-based perioperative chemotherapy is associated with a relatively high
      number of adverse events. Although this toxicity did not affect the esophageal
      resectability rate, this regimen should be used with caution in this patient
      population.

PMID- 25564158
TI  - Sarcopenia is a Negative Prognostic Factor After Curative Resection of Colorectal
      Cancer.
AB  - BACKGROUND: Skeletal muscle depletion (sarcopenia) is closely associated with
      limited physical ability and high mortality. This study was performed to evaluate
      the prognostic significance of skeletal muscle depletion in patients with
      resectable stage I-III colorectal cancer (CRC). METHODS: We conducted a
      retrospective analysis of 220 consecutive patients with stage I-III CRC who
      underwent curative resection. The skeletal muscle cross-sectional area was
      measured by preoperative computed tomography. The lowest sex-specific quartile of
      skeletal muscle mass was classified as sarcopenia. Factors contributing to
      recurrence-free survival (RFS) were analyzed by univariate and multivariate Cox
      proportional hazard models. RESULTS: Of 220 patients who met our inclusion
      criteria, 55 (25 %) had sarcopenia. The median follow-up duration was 41.4
      months. Patients with sarcopenia were younger and had higher carcinoembryonic
      antigen levels than patients without sarcopenia. RFS and overall survival (OS)
      were significantly shorter in patients with sarcopenia than those without (5-year
      RFS, 56 vs. 79 %, log-rank p = 0.006; 5-year OS, 68 vs. 85 %, log-rank p =
      0.015). Multivariate Cox regression analysis revealed that sarcopenia was
      independently associated with shorter RFS (hazard ratio [HR] 2.176; 95 %
      confidence interval [CI] 1.200-3.943; p = 0.010) and OS (HR 2.270; 95 % CI 1.147
      4.494; p = 0.019). The influence of sarcopenia on patient outcome was modified by
      age at surgery (p value for interaction = 0.026); sarcopenia was associated with
      a poor prognosis, especially in young patients (log-rank p < 0.001). CONCLUSIONS:
      Sarcopenia negatively impacts survival in patients undergoing curative resection
      for stage I-III CRC.

PMID- 25564157
TI  - The Role of Stereotactic Body Radiation Therapy for Pancreatic Cancer: A Single
      Institution Experience.
AB  - BACKGROUND: Stereotactic body radiation therapy (SBRT) is a promising option for
      patients with pancreatic cancer (PCA); however, limited data support its
      efficacy. This study reviews our institutional experience of SBRT in the
      treatment of locally advanced (LAPC) and borderline resectable (BRPC) PCA.
      METHODS: Charts of all PCA patients receiving SBRT at our institution from 2010
      to 2014 were reviewed. Most patients received pre-SBRT chemotherapy. Primary
      endpoints included overall survival (OS) and local progression-free survival
      (LPFS). Patients received a total dose of 25-33 Gy in five fractions. RESULTS: A
      total of 88 patients were included in the analysis, 74 with LAPC and 14 with
      BRPC. The median age at diagnosis was 67.2 years, and median follow-up from date
      of diagnosis for LAPC and BRPC patients was 14.5 and 10.3 months, respectively.
      Median OS from date of diagnosis was 18.4 months (LAPC, 18.4 mo; BRPC, 14.4 mo)
      and median PFS was 9.8 months (95 % CI 8.0-12.3). Acute toxicity was minimal with
      only three patients (3.4 %) experiencing acute grade >=3 toxicity. Late grade >=2
      gastrointestinal toxicity was seen in five patients (5.7 %). Of the 19 patients
      (21.6 %) who underwent surgery, 79 % were LAPC patients and 84 % had margin
      negative resections. CONCLUSIONS: Chemotherapy followed by SBRT in patients with
      LAPC and BRPC resulted in minimal acute and late toxicity. A large proportion of
      patients underwent surgical resection despite limited radiographic response to
      therapy. Further refinements in the integration of chemotherapy, SBRT, and
      surgery might offer additional advancements toward optimizing patient outcomes.

PMID- 25564159
TI  - Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for
      children, adolescents, and young adults: the first 50 cases.
AB  - BACKGROUND: Extensive peritoneal metastatic disease is rare in children. Although
      usually manifested as carcinomatosis in adults, sarcomatosis is more common in
      children. The authors began a pediatric hyperthermic intraperitoneal chemotherapy
      (HIPEC) program, and this report describes their initial results from the first
      50 pediatric, adolescent, and young adult patients. METHODS: A single
      institution, retrospective study investigated the first 50 cytoreductive
      surgeries and HIPEC by one surgeon for patients 3-21 years of age. The HIPEC was
      added to chemotherapy and radiotherapy treatment. Demographics, outcome, and
      complications were recorded. RESULTS: The median follow-up period for the
      surviving patients was 21.9 months. The most common diagnoses were desmoplastic
      small round cell tumor (n = 21), rhabdomyosarcoma (n = 7), mesothelioma (n = 4),
      and other carcinoma (n = 17). Multivariate analysis showed that patients treated
      with HIPEC and an incomplete cytoreduction had a greater risk for recurrence than
      those who had a complete cytoreduction (p = 0.0002). The patients with a higher
      peritoneal cancer index (PCI) (i.e., a large tumor burden) had a median overall
      survival (OS) time of 19.9 months relative to the patients with a lower PCI
      score, who had a median OS of 34 months (p = 0.049). The patients without
      complete cytoreduction had a median OS of 7.1 months compared with 31.4 months
      for the patients with complete cytoreduction (p = 0.012). No perioperative
      mortalities occurred. The incidence of major complications was 28 %. CONCLUSION:
      Cytoreductive surgery and HIPEC with a programmatic approach for patients 3-21
      years of age is unique. The best outcome was experienced by patients with
      desmoplastic small round cell tumor and those with complete cytoreduction.
      Complete cytoreduction for patients without disease outside the abdominal cavity
      at the time of surgery affords the best outcome.

PMID- 25564160
TI  - Strategies to Increase the Resectability of Patients with Colorectal Liver
      Metastases: A Multi-center Case-Match Analysis of ALPPS and Conventional Two
      Stage Hepatectomy.
AB  - BACKGROUND: Two-stage hepatectomy (TSH) is well established for the treatment of
      patients who have colorectal cancer liver metastases (CRLM) with a small liver
      remnant. The technique of associating liver partitioning and portal vein
      occlusion for staged hepatectomy (ALPPS) has been advocated as a novel tool to
      increase resectability. Using a case-match design, this study aimed to compare
      TSH and ALPPS for patients with CRLM. METHODS: All patients undergoing ALPPS for
      CRLM at three major hepatobiliary centers in Italy (ALPPS group) were compared in
      a case-match analysis with patients undergoing TSH (TSH group) at a single
      institution. The groups were matched with a 1:3 ratio using propensity scores
      based on covariates representing severity of metastatic disease. The main end
      points of the study were feasibility of complete resection and intra- and
      postoperative outcomes. RESULTS: The two treatments did not differ significantly
      in feasibility. Two patients in the TSH group dropped out compared with no
      patients in the ALPPS group. A comparable volume gain in future liver remnant
      (FLR) was obtained in the ALPPS and TSH groups (47 vs. 41 %, nonsignificant
      difference) but during a shorter interval in ALPPS group. The overall and major
      complication rate was significantly higher after stage 2 in the ALPPS group
      (Clavien >= 3a: 41.7 vs. 17.6 % in TSH group; p = 0.025). CONCLUSION: The
      feasibility of resection using ALPPS compared with TSH for CRLM was not
      significantly greater, but perioperative complications were increased. Therefore,
      ALPPS should be proposed to patients with caution and warnings. Currently, TSH
      remains the standard approach for performing R0 resection in patients with
      advanced CRLM and inadequate FLR.

PMID- 25564161
TI  - Presence of Concomitant Non-muscle-invasive Bladder Cancer in Chinese Patients
      with Upper Tract Urothelial Carcinoma: Risk Factors, Characteristics, and
      Predictive Value.
AB  - PURPOSE: To explore the characteristics, predictive risk factors, and prognostic
      effect of concomitant non-muscle-invasive bladder cancer (NMIBC) in patients with
      upper tract urothelial carcinoma (UTUC). METHODS: We evaluated 727 consecutive
      UTUC patients treated with radical resection between 2000 and 2012 in a high
      volume center of China. Preoperative cystoscopy was performed in all patients.
      Patients with previous or concomitant total cystectomy were excluded. RESULTS:
      Overall, 73 patients (10.0 %) had NMIBC. Concomitant NMIBC was associated with
      previous bladder cancer (p = 0.003), tumor located in ureter (p = 0.008),
      multifocality (p < 0.001), and preoperative renal insufficiency (p = 0.023). The
      presence of concomitant NMIBC was predictive for lower tumor stage (p = 0.019),
      papillary architecture (p = 0.023), and organ-confined disease (pT < 3 and N-, p
      = 0.006). The median follow-up duration was 57 months. The presence of
      concomitant NMIBC was a risk factor for bladder recurrence (p < 0.001), and
      particularly in patients with non-muscle-invasive UTUCs, it affects cancer
      specific survival (odds ratio 1.614, p = 0.030) and contralateral recurrence
      (odds ratio, 1.907, p = 0.016). Most concomitant NMIBC were found at the lateral
      wall or bladder neck, while most intravesical recurrences occurred near the site
      of surgery or posterior wall. CONCLUSIONS: The most common site for concomitant
      NMIBC was lateral wall and bladder neck, and previous bladder cancer, tumor
      located in ureter, tumor multifocality, and preoperative renal insufficiency were
      risk factors for concomitant NMIBC. The presence of concomitant NMIBC is
      predictive for relative better pathologic outcomes but higher rate of bladder
      recurrence, while the effect on postoperative survival was limited with patients
      early-stage UTUCs. The potential mechanisms need further investigation.

PMID- 25564162
TI  - French Multicenter Study Evaluating the Risk of Lymph Node Metastases in Early
      Stage Endometrial Cancer: Contribution of a Risk Scoring System.
AB  - BACKGROUND: This study was designed to develop a risk scoring system (RSS) for
      predicting lymph node (LN) metastases in patients with early-stage endometrial
      cancer (EC). METHODS: Data of 457 patients with early-stage EC who received
      primary surgical treatment between January 2001 and December 2012 were abstracted
      from a prospective, multicentre database (training set). A risk model based on
      factors impacting LN metastases was developed. To assess the discrimination of
      the RSS, both internal by the bootstrap approach and external validation
      (validation set) were adopted. RESULTS: Overall the LN metastasis rate was 11.8 %
      (54/457). LN metastases were associated with five variables: age >=60 years,
      histological grade 3 and/or type 2, primary tumor diameter >=1.5 cm, depth of
      myometrial invasion >=50 %, and the positive lymphovascular space involvement
      status. These variables were included in the RSS and assigned scores ranging from
      0 to 9. The discrimination of the RSS was 0.81 [95 % confidence interval (CI)
      0.78-0.84] in the training set. The area under the curve of the receiver
      operating characteristics for predicting LN metastases after internal and
      external validation was 0.80 (95 % CI 0.77-0.83) and 0.85 (95 % CI 0.81-0.89),
      respectively. A total score of 6 points corresponded to the optimal threshold of
      the RSS with a rate of LN metastases of 7.5 % (29/385) and 34.7 % (25/72) for low
      risk (<=6 points) and high-risk patients (>6 points), respectively. At this
      threshold, the diagnostic accuracy was 83 %. CONCLUSIONS: This RSS could be
      useful in clinical practice to determine which patients with early-stage EC
      should benefit from secondary surgical staging including complete
      lymphadenectomy.

PMID- 25564163
TI  - Clinical Significance of SIP1 and E-cadherin in Patients with Esophageal Squamous
      Cell Carcinoma.
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT), when epithelial cells
      convert to mesenchymal cells, influences cancer invasion and metastasis. Smad
      interacting protein 1 (SIP1) is an EMT trigger, which is inversely correlated
      with E-cadherin in some carcinomas. To elucidate the role of SIP1 in esophageal
      squamous cell carcinoma (ESCC), the status of EMT and the clinicopathological
      features were evaluated. METHODS: Immunohistochemical (IHC) analyses of 111 human
      ESCC tissue specimens for SIP1 and E-cadherin were performed, and the
      relationships between the expression and clinicopathological features were
      evaluated. RESULTS: IHC analyses of esophageal tumors showed the expression of
      SIP1 and E-cadherin to be significantly inversely correlated. Significant
      correlations between the SIP1 expression and clinicopathological variables such
      as differentiation, depth of invasion, vascular invasion, and pathological stage
      were also seen. Conversely, tumors with a weak expression of E-cadherin tended to
      exhibit greater histological differentiation. Logistic regression analyses
      revealed a positive SIP1 expression, lymphatic invasion, and vascular invasion to
      be factors predicting lymph node (LN) metastasis. Univariate survival analyses
      revealed a positive SIP1 expression predicted a poorer overall survival than a
      negative expression. CONCLUSION: These results suggest that SIP1 is correlated
      with LN metastasis and may therefore be an independent marker for metastasis in
      patients with ESCC.

PMID- 25564165
TI  - Early and Late Outcomes of Surgery for Locally Recurrent Rectal Cancer: A
      Prospective 10-Year Study in the Total Mesorectal Excision Era.
AB  - AIM: The aim of this study was to assess the outcome of all locally recurrent
      rectal cancer (LRRC) patients who were referred to a tertiary care center. The
      study examined LRRC patients who underwent surgery after prior total mesorectal
      excision. METHOD: The data of 213 consecutive LRRC patients who were registered
      in a database between 2001 and 2010 were accessed. RESULTS: A total of 115
      patients (54 %) with a median age of 63 (range 34-81) years underwent tumor
      resection. The 30-day mortality rate was 0.8 % (95 % CI 0.02-4 %), and the
      complication rate was 42 % (95 % CI 33-51 %). R0 resection was achieved in 70
      patients (61 %), R1 resection in 38 patients (33 %), and R2 resection in 7
      patients (6 %). The 3- and 5-year survival rates for R0 resections were 55 % (95
      % CI 41-66) and 40 % (95 % CI 26-53), respectively; 42 % (95 % CI 26-58) and 16 %
      (95 % CI 5-31), respectively, for R1 resections; no patients who received an R2
      resection survived to the 3-year mark. Patients with prior abdominoperineal
      excision (APE) had significantly poorer survival rates than patients with prior
      resection with anastomosis (p = 0.02). CONCLUSION: Acceptable long-term survival
      can be achieved for patients undergoing surgery for LRRC, but radical resection
      is mandatory. Prior APE was associated with poorer survival rates.

PMID- 25564166
TI  - A Patient-Centered Approach to Wait Times in the Surgical Management of Breast
      Cancer in the Province of Ontario.
AB  - BACKGROUND: Wait time for breast cancer is an important contributor to cancer
      outcomes and patient satisfaction. This study sought to define a patient-centered
      wait time by measuring the time from the first abnormal imaging to definitive
      surgery. The authors hypothesized that multiple preoperative investigations
      significantly increase the patient-centered wait time. METHODS: A retrospective
      analysis of prospectively maintained databases at the Institute for Clinical and
      Evaluative Sciences in Ontario, Canada was performed. Women undergoing primary
      surgery for invasive breast cancer from 2003 to 2011 were evaluated. The median
      wait time between the first abnormal imaging and definitive surgery was
      calculated. Uni- and multivariable analyses were performed to identify
      characteristics of the patients, treating institution, and diagnostic pathway
      that contribute significantly to the patient-centered wait time. RESULTS: Our
      final cohort consisted of 42,179 patients: 31,837 (75 %) who had breast
      conserving surgery and 10,342 (25 %) who underwent mastectomy. The median wait
      time from the first abnormal imaging to definitive surgery was 52 days
      (intraquartile range 35-76 days). In adjusted analysis, older patient age, later
      year of surgery, additional preoperative imaging, and biopsies beyond those
      required for diagnosis significantly and independently extended the surgical wait
      time. Preoperative consultations and institutional factors such as volume of
      breast surgery performed and geographic location also independently had an impact
      on surgical wait time. CONCLUSIONS: This study defined a novel patient-centered
      measure of surgical wait time that more fully embraces the wait experienced by
      the patient. Many common preoperative interventions had a significant impact on
      overall wait time experienced by the patient. Evidence-based quality initiatives
      to coordinate appropriate investigations are needed to reduce wait times.

PMID- 25564164
TI  - Angiopoietin-Like Protein 2 Acts as a Novel Biomarker for Diagnosis and Prognosis
      in Patients with Esophageal Cancer.
AB  - BACKGROUND: Angiopoietin-like protein 2 (ANGPTL2) mediates chronic inflammation.
      Tumor cell-derived ANGPTL2 promotes tumor invasion and angiogenesis.
      Overexpression of ANGPTL2 in tumor cells is associated with tumor progression and
      has been recognized in lung, breast, colon, and gastric cancer. However, to our
      knowledge the functional and clinical significance of ANGPTL2 expression has not
      been investigated in patients with esophageal cancer (EC). METHODS: First, in
      vitro assays were performed for functional analysis of ANGPTL2 using small
      interfering RNA. Next, ANGPTL2 expression in EC tissues (n = 71) was evaluated by
      immunohistochemistry (IHC in patients with EC (n = 71). Finally, serum ANGPLT2
      levels from patients with EC (n = 71) and healthy controls (n = 35) were
      evaluated using enzyme-linked immunosorbent assay. RESULTS: Knockdown of ANGPTL2
      expression decreased the proliferative, invasive, and migration capacity in EC
      cell lines. ANGPTL2 expression in EC tissues was significantly elevated in
      patients with a high T stage, squamous cell carcinoma, and high TNM stage.
      Patients with high ANGPTL2 expression had significantly poorer overall and
      disease-free survival than those with low expression. Furthermore, high ANGPTL2
      expression in EC tissues was an independent predictive marker for a poor
      prognosis. On the other hand, the serum ANGPTL2 level in patients with EC was
      significantly higher than that in healthy controls, and allowed for highly
      accurate discrimination between patients with and without EC. However, no
      significant association between serum ANGPTL2 levels and clinicopathological
      findings was observed in patients with EC. CONCLUSIONS: We have demonstrated
      novel evidence for the clinical significance of ANGPTL2 as a biomarker in
      patients with EC.

PMID- 25564167
TI  - The Effect of Adjuvant Trastuzumab on Locoregional Recurrence of Human Epidermal
      Growth Factor Receptor 2-Positive Breast Cancer Treated with Mastectomy.
AB  - BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpression was
      associated with locoregional recurrence (LRR) in the preadjuvant trastuzumab era.
      This study aimed to examine the effect of trastuzumab on LRR in mastectomy
      patients and whether it varied with postmastectomy radiation (PMRT). METHODS:
      From the authors' institutional database, 501 women with stages I-III HER2
      positive breast cancer who underwent mastectomy from 1998 to 2007 were
      identified. A landmark analysis was performed to compare two cohorts: 170 women
      who received trastuzumab and 281 who did not. Kaplan-Meier methods were used to
      estimate locoregional recurrence-free survival (LRRFS). A propensity score
      analysis was used to balance the treatment groups with respect to multiple
      covariates. Analogous methods were used to study the effect of PMRT. RESULTS: The
      women in the trastuzumab group were more likely to be node positive and to
      receive systemic therapy or PMRT (p < 0.01). The 5-year LRRFS was 98 % in the
      trastuzumab troup versus 94 % in the no trastuzumab group [hazard ratio (HR)
      0.31; 95 % confidence interval (CI) 0.09-1.09; p = 0.07]. After adjustment for
      multiple covariates, including receipt of chemotherapy and PMRT, trastuzumab
      decreased LRR rates (HR 0.21; 95 % CI 0.04-0.94; p = 0.04). Among the women who
      received PMRT, trastuzumab reduced the 5-year LRR rate (0 vs 5 %; p = 0.06).
      Among those who did not receive PMRT, trastuzumab did not significantly decrease
      LRR (3 vs 6 %; p = 0.26). CONCLUSION: High rates of locoregional control (5-year
      rate, 98 %) were observed among patients who received trastuzumab and mastectomy
      +/- PMRT. Trastuzumab decreased LRR in HER2-positive women who received
      mastectomy and PMRT, suggesting that the largest benefit is seen in a higher-risk
      subset of patients.

PMID- 25564168
TI  - Plate exposure after anterolateral thigh free-flap reconstruction in head and
      neck cancer patients with composite mandibular defects.
AB  - BACKGROUND: This study aimed to identify the risk factors for postoperative plate
      exposure in head and neck cancer patients with composite mandibular defects
      undergoing tumor ablation followed by bridging plate and anterolateral thigh
      (ALT) flap transfer. METHODS: Between January 2007 and June 2012, 1,452 patients
      who underwent free tissue transfer after head and neck cancer ablation were
      retrospectively reviewed. Only ALT flap coverage with a bridging plate for
      segmental mandibular defects was included. The Jewer's classification was used to
      define the type of mandibular defect. RESULTS: The study enrolled 123 men and 7
      women. The incidence of plate exposure was 37.7 % (49/130). The follow-up time
      ranged from 0.5 to 5.4 years (mean, 2.4 years). The 5-year probability of a plate
      exposure-free rate was 32.8 % for the patients with postoperative radiotherapy
      (RT) (n = 33) and 64.3 % for the patients without it (n = 97). Patients
      reconstructed with a fasciocutaneous or chimeric type of ALT flap had higher
      rates of plate exposure than those reconstructed with a musculocutaneous type of
      ALT flap (p = 0.002). As shown by logistic regression, the significant predictive
      risk factors for postoperative plate exposure still were postoperative RT
      [adjusted odds ratio (OR) 2.76, 95 % confidence interval (CI) 1.09-6.99, p =
      0.031] and intraoperative blood loss (adjusted OR 2.37, 95 % CI 1.13-4.99, p =
      0.022). CONCLUSIONS: The type of ALT flap, postoperative RT, and intraoperative
      blood loss were the predisposing factors for increased risk of postoperative
      plate exposure in the specific disease group.

PMID- 25564169
TI  - Targeting HIF1alpha peri-operatively increased post-surgery survival in a tongue
      cancer animal model.
AB  - BACKGROUND: The purpose of the present study was to evaluate the relationship
      between hypoxia-inducible factor 1 alpha subunit (HIF1alpha) and tumor initiation
      in squamous cell carcinoma cell lines and whether targeting HIF1alpha
      perioperatively might exert positive effects on survival or recurrence in an
      animal model. METHODS: The expression of HIF1alpha and tumorigenic potential in
      nude mice was compared using human head and neck squamous cell carcinoma cell
      lines (SNU1041, SNU1066, SNU1076, PCI01, PCI13, PCI50). A recurrent tongue cancer
      model was established by first injecting tumor cells in the lateral tongue and
      then excising the tongue masses for replanting in the neck. The effect of
      HIF1alpha inhibitors was assessed using this animal model. RESULTS: We observed
      good correlation between tumorigenic potential and HIF1alpha nuclear expression
      in the cell lines tested. Furthermore, knockdown of HIF1alpha inhibited tumor
      growth in the animal model. After in vitro testing of five HIF1alpha inhibitors,
      echinomycin and LAQ824 were selected for the animal study. Pre- and postoperative
      treatment with echinomycin showed significant improvement in postsurgery survival
      and recurrence. CONCLUSIONS: Our results suggested that adjuvant targeting of
      HIF1alpha before and after surgery could be a new targeted therapy strategy for
      squamous cell carcinoma.

PMID- 25564170
TI  - Clinical presentation of patients with a thyroid follicular neoplasm: are there
      preoperative predictors of malignancy?
AB  - BACKGROUND: Studies examining differences in presentation of patients with benign
      [follicular adenoma (FA)] and malignant follicular thyroid neoplasms [follicular
      thyroid carcinoma (FTC) or follicular variant papillary thyroid carcinoma
      (FVPTC)] include only one or two of these subtypes, and none has considered
      clinical, cytological, and sonographic features together. We therefore examined
      presenting clinical features of all benign and malignant follicular neoplasm
      subtypes in an attempt to identify predictors of malignancy. METHODS: Consecutive
      patients with a surgically resected follicular thyroid neoplasm at a tertiary
      hospital from 2005 to 2013 were reviewed. Age, gender, symptoms, history,
      physical findings, nodule size, sonographic, cytologic, and final pathologic
      results were recorded. Multivariate logistic regression was used to determine
      variables that contributed to a diagnosis of malignant follicular neoplasm.
      RESULTS: A total of 616 patients (163 males, 453 females) presented with 441 FAs,
      17 FTCs, and 158 FVPTCs. On multivariate analysis, male sex [odds ratio (OR)
      1.87, p = 0.008], family history of thyroid cancer (OR 5.16, p < 0.001), and
      history of head and neck radiation (OR 2.01, p = 0.04) were associated with an
      increased odds of malignancy; age >45 (OR 2.03, p = 0.001), dysphagia (OR 3.48, p
      = 0.001) or pressure sensation (OR 3.00, p = 003), concomitant hyperthyroidism
      (OR 4.76, p = 0.01), nodules >=4 cm (OR 3.68, p < 0.001), and multinodularity on
      physical examination (OR 1.93, p = 0.004) were associated with an increased odds
      of a benign lesion. CONCLUSIONS: Independent clinical predictors exist that might
      be helpful in preoperative differentiation of benign and malignant follicular
      neoplasms. A combination of these predictors with both FNA and molecular results
      may help us to improve the clinical management of patients with follicular
      thyroid lesions.

PMID- 25564171
TI  - Overutilization and Cost of Advanced Imaging for Long-Bone Cartilaginous Lesions.
AB  - BACKGROUND: The prevalence and cost of unnecessary advanced imaging studies (AIS)
      in the evaluation of long bone cartilaginous lesions have not been studied
      previously. METHODS: A total of 105 enchondromas and 19 chondrosarcomas arising
      in long bones from July 2008 until April 2012 in 121 patients were reviewed.
      Advanced imaging was defined as MRI, CT, bone scan, skeletal survey, or CT
      biopsy. Two blinded radiologists independently reviewed the initial imaging study
      and determined if further imaging was indicated based on that imaging study
      alone. The cost of imaging was taken from our institution's global charge list.
      Imaging was deemed unnecessary if it was not recommended by our radiologists
      after review of the initial imaging study. The difference in cost was calculated
      by subtracting the cost of imaging recommended by each radiologist from the cost
      of unnecessary imaging. The sensitivity and specificity for distinguishing
      enchondromas from chondrosarcomas was calculated. A minimum of 2 years from
      diagnosis of an enchondroma was required to monitor for malignant transformation.
      RESULTS: Of patients diagnosed with an enchondroma, 85 % presented with AIS. The
      average enchondroma patient presented with one unnecessary AIS. The radiologists'
      interpretations agreed 85 % of the time for enchondromas and 100 % for
      chondrosarcomas. The sensitivity and specificity for distinguishing enchondromas
      from chondrosarcomas was 95 % for one radiologist and 87 and 95 % for the other.
      The average unnecessary cost per enchondroma patient was $1,346.18. CONCLUSIONS:
      Unnecessary AIS are frequently performed and are a significant source of expense.
      The imaging algorithms outlined in this study may reduce unnecessary AIS.

PMID- 25564172
TI  - Immediate Reconstruction of the Radiated Breast: Recent Trends Contrary to
      Traditional Standards.
AB  - BACKGROUND: Immediate, implant-only breast reconstruction is traditionally
      discouraged in patients who receive radiation. It is not clear whether this
      widely recognized mantra of breast reconstruction is observed in practice. The
      purpose of this study was to evaluate immediate reconstruction trends and
      practices in patients who have undergone mastectomy and radiation therapy.
      METHODS: Female patients with unilateral breast cancer who required radiation in
      addition to mastectomy were extracted from the Surveillance, Epidemiology, and
      End Results (SEER) database from 2000 through 2010. Patients who underwent
      immediate reconstruction were identified and analyzed. Univariate and logistic
      regression analyses were performed to study the relationship between
      reconstructive method and patient demographic and oncologic characteristics.
      RESULTS: A total of 5,481 female patients who underwent radiation and breast
      reconstruction were included for analysis. Postmastectomy radiation therapy was
      performed in 98.3 % of the patients. The immediate breast reconstruction rate
      among patients requiring radiation increased from 13.6 to 25.1 %. The percentage
      of reconstructed patients who had implant-only reconstruction increased from 27
      to 52 % (p < 0.001) with a decrease in tissue-only reconstruction from 56 to 32 %
      (p < 0.001). In regression analysis, the odds of implant reconstruction over
      autologous reconstruction increased each year by an odds ratio of 1.13 (95 % CI
      1.10-1.15). CONCLUSIONS: The frequency of immediate reconstruction continues to
      increase in the setting of postmastectomy radiation therapy, with immediate
      implant-based reconstruction representing the most commonly utilized method,
      contrary to traditional recommendations. These findings likely reflect changing
      attitudes towards implant reconstruction in the setting of planned postmastectomy
      radiation.

PMID- 25564174
TI  - Comparison of Reduced Port Totally Laparoscopic Distal Gastrectomy (Duet TLDG)
      and Conventional Laparoscopic-Assisted Distal Gastrectomy.
AB  - BACKGROUND: Laparoscopic-assisted distal gastrectomy (LADG) is a treatment method
      for patients with early gastric cancer; however, single or reduced port LADG has
      been rarely reported. This study aimed to compare surgical outcomes of patients
      with gastric cancer undergoing reduced port totally laparoscopic distal
      gastrectomy (duet TLDG) to those of patients undergoing conventional LADG.
      METHODS: This retrospective study included 202 patients with early gastric cancer
      who underwent duet TLDG (102 patients) or conventional LADG (100 patients) at
      Samsung Medical Center between October 2013 and April 2014. RESULTS: Operating
      time was shorter for duet TLDG than for conventional LADG (mean +/- SD 121.1 +/-
      19.3 min vs. 153.0 +/- 38.1 min, P < 0.001). Blood loss during surgery was
      similar between duet TLDG and conventional LADG groups (91.4 +/- 68.4 mL vs. 85.4
      +/- 59.8 mL, P = 0.506). Complication rates in the duet TLDG and conventional
      LADG groups were similar (15.7 % vs. 10.0 %, P = 0.294). The quality of lymph
      node dissection, including the median number of nodes dissected (median [range]
      duet TLDG vs. conventional LADG, 36 [17-76] vs. 34 [15-64], P = 0.570) and number
      of dissected nodes in each lymph node station, did not differ between groups. The
      median postoperative hospital stay was similar (7 [7-23] days vs. 7 [6-9], P =
      0.423). Pain scores were 3.6, 3.2, and 2.8, and 3.7, 3.1, and 2.6, at
      postoperative days 1, 3, and 5, respectively, in the duet TLDG and conventional
      LADG groups (P = 0.408, 0.250, and 0.130). CONCLUSIONS: Reduced port duet TLDG
      for early gastric cancer is feasible in terms of patient safety and quality of
      lymph node dissection.

PMID- 25564173
TI  - Additional Primary Malignancies in Patients with Gastrointestinal Stromal Tumor
      (GIST): A Clinicopathologic Study of 260 Patients with Molecular Analysis and
      Review of the Literature.
AB  - BACKGROUND: The incidence of other primary neoplasms in gastrointestinal stromal
      tumor (GIST) patients is relatively high. Our aim was to better characterize the
      clinicopathologic and molecular relationships in a cohort of GIST patients.
      METHODS: All GIST patients with tumor samples sent for molecular testing were
      identified via electronic medical records. Clinicopathologic characteristics of
      GIST and additional primary malignancies were analyzed. RESULTS: Of 260 patients,
      50 (19 %) had at least one additional primary malignancy. In 33 patients,
      separate primary neoplasms predated their GIST diagnosis and most commonly
      included: prostate (n = 9), breast (n = 8), and hematologic (n = 5). Renal (n =
      4) and hematologic (n = 3) malignancies were the most frequent cancers identified
      after GIST diagnosis. The majority (8 of 12, 66 %) of malignancies diagnosed
      after GIST were found incidentally. Patients who developed other malignancies
      after GIST more often had KIT exon 11 mutations (100 vs. 66 %, P = 0.01). In
      comparison to patients with only GIST, patients with a second primary neoplasm of
      any chronology had GISTs with increased mitotic rate (>=5 per 50 high-power
      fields) (P = 0.0006). Literature review revealed colorectal cancer, gastric,
      prostate, renal, leukemia, and desmoid-type fibromatosis as the most common
      secondary neoplasms. CONCLUSIONS: Nineteen percent of GIST patients develop other
      malignancies. This is the first report to describe a relationship between
      additional primary malignancy and both mutation and mitotic rate of GIST.
      Although the basis of these relationships remains to be investigated, caution in
      the clinical management of GIST patients with additional lesions is warranted.

PMID- 25564175
TI  - Growing Use of Mastectomy for Ductal Carcinoma-In Situ of the Breast Among Young
      Women in the United States.
AB  - BACKGROUND: Ductal carcinoma-in situ (DCIS) is a preinvasive form of breast
      cancer associated with excellent outcomes after either mastectomy or breast
      conservation therapy. Previous studies have demonstrated declining rates of
      mastectomy. However, it is unclear how this pattern has changed in recent years.
      METHODS: Women with DCIS were identified within the National Cancer Data Base.
      Patients treated with lumpectomy with or without radiotherapy were compared to
      women treated with mastectomy on the basis of demographic, clinicopathologic, and
      reporting facility details using chi (2) tests and multivariable logistic
      regression modeling to identify factors that may influence surgical choice.
      Changes in the proportion of women receiving contralateral prophylactic
      mastectomy (CPM) were assessed in a similar fashion. RESULTS: We identified
      212,936 women diagnosed with DCIS between 1998 and 2011. Lumpectomy was performed
      in 68 % (144,681) of patients. Mastectomy rates initially declined from 1998 (36
      %) through 2004 (28 %), before increasing again through 2011 (33 %). Younger
      patient age, greater medical comorbidity, more extensive disease, higher tumor
      grade, treatment at an academic facility, and greater distance from the reporting
      facility were associated with heightened use of mastectomy (all p < 0.001). CPM
      also increased over time, particularly among younger patients, on multivariate
      analysis (p < 0.001). CONCLUSIONS: Mastectomy utilization appears to be rising
      between 2004 and 2011, particularly among younger patients and those with higher
      risk histopathologic features. CPM is increasing in a similar fashion. Further
      research is needed to understand the drivers of this change.

PMID- 25564176
TI  - Comparison of transthoracic esophagectomy with definitive chemoradiotherapy as
      initial treatment for patients with esophageal squamous cell carcinoma who could
      tolerate transthoracic esophagectomy.
AB  - BACKGROUND: The oncological outcomes of transthoracic esophagectomy (TTE) and
      definitive chemoradiotherapy (dCRT) as initial treatment in patients with
      esophageal squamous cell carcinoma (ESCC) who could tolerate TTE remains unclear.
      METHODS: Consecutive patients histologically diagnosed with stage I/II/III ESCC
      (excluding cT4 or cN3) or stage IV ESCC due to supraclavicular lymph node
      metastasis were eligible for inclusion in this retrospective study. To select
      patients who could tolerate TTE, respiratory function, Eastern Cooperative
      Oncology Group performance status, and preoperative complications were
      considered. Patient characteristics, recurrence-free survival (RFS), 3- and 5
      year overall survival (OS), pattern of recurrence, and treatments after initial
      treatment failure were investigated. RESULTS: Overall, 112 patients were included
      in the TTE group and 65 were included in the dCRT group. No significant
      differences were observed in patient characteristics and clinical stage between
      the TTE and dCRT groups (stage I/II/III/IV of 29/27/46/10 in the TTE group and
      23/15/20/7 in the dCRT group). The R0 resection rate was 87 % in the TTE group,
      and complete response rate was 68 % in the dCRT group. In intention-to-treat
      analysis, there was no significant difference in RFS. In contrast, 3-year OS of
      non-stage IA patients was significantly longer in the TTE group than the dCRT
      group (TTE 66.9 %; dCRT 49.8 %; p = 0.023). In non-stage IA patients, after
      initial treatment failure significantly more patients could undergo local
      treatment (radiotherapy or surgery in the TTE group; surgery or endoscopic
      resection or photodynamic therapy in the dCRT group) in the TTE group than the
      dCRT group (TTE 74 %; dCRT 40 %; p = 0.003). CONCLUSIONS: In locally advanced
      ESCC patients who could tolerate TTE, TTE extended 3-year OS, which might have
      been encouraged by utilizing local treatment after initial treatment failure.

PMID- 25564177
TI  - Sentinel Lymph Node Dissection in Locally Recurrent Breast Cancer.
AB  - BACKGROUND: The aim of this study was to investigate the use of sentinel lymph
      node dissection (SLND) in the treatment of patients with locally recurrent breast
      cancer. METHODS: A total of 147 patients with locally recurrent breast cancer
      were included from five different breast surgery departments in Denmark. Data on
      previous breast and axillary surgery, adjuvant treatment, second operation in the
      breast and axilla, and lymphoscintigraphy were collected retrospectively from the
      original patient files. RESULTS: SLND after recurrence (SLNDAR) was successful in
      72 of 144 patients (50 %). The detection rate was significantly higher after
      previous SLND (66 %) compared with previous ALND (34 %) [p = 0.0001]. Thirty
      seven patients (51 %) who had previous SLND had a negative sentinel node. These
      patients could be spared an ALND. Six patients (8 %) who had a previous ALND had
      a metastatic sentinel node at recurrence; 17 % of patients had a sentinel node
      located outside the ipsilateral axilla; and eight patients with negative sentinel
      node at SLNDAR underwent completion ALND. None of these patients had metastases
      at completion ALND, corresponding to a false negative rate of 0 %. CONCLUSIONS:
      SLNDAR seems to be a feasible procedure in locally recurrent breast cancer and
      can spare a clinically significant number of patients an unnecessary ALND and the
      following risk of sequelae. In patients who had previous ALND, SLNDAR identified
      metastases that would have been overlooked following the current guidelines. A
      large proportion of patients had aberrant drainage, suggesting a need for
      lymphoscintigraphy.

PMID- 25564178
TI  - Modern Treatment of Rectal Cancer Closes the Gap Between Common Adenocarcinoma
      and Mucinous Carcinoma.
AB  - BACKGROUND: Mucinous carcinoma (MC) is a distinct form of rectal cancer (RC)
      comprising 10 % of all cases and has been associated with an impaired prognosis
      compared with non-mucinous adenocarcinoma (AC). The benefit of today's modern
      treatment for MC patients is unknown but a prospective randomized trial to answer
      this does not seem feasible. This study provides an analysis of the modern
      treatment of rectal MC and efficacy of preoperative therapies for MC patients.
      METHODS: Data from three large (trial) cohorts were used. Data from the
      Netherlands Cancer Registry (NCR) were used to analyze the prognosis of RC
      patients over time (N = 38,035). To study the benefit of preoperative short-term
      radiotherapy, patients from the total mesorectal excision (TME) trial (N = 1,530)
      were selected, and the benefit from preoperative chemoradiotherapy was analyzed
      with data on 540 locally advanced RC (LARC) patients from two hospitals. RESULTS:
      Data from the NCR confirmed that 5-year overall survival for MC was significantly
      worse from 1989 to 1998, but no longer different from AC from 1999 onwards. MC
      patients had a higher rate of positive circumferential resection margin than AC
      patients (TME trial 27.2 vs. 16.5 %, p = 0.006; LARC cohort 34.5 vs. 9.8 %, p <
      0.0001), but there was no difference in outcome between MC and AC patients after
      preoperative short-term radiotherapy or chemoradiotherapy. CONCLUSIONS: Modern
      treatment of RC has benefited MC patients, leading to equal survival for MC and
      AC patients. Enhancements in the fields of imaging and quality of surgery have
      improved outcome and preoperative therapies should be recommended for both
      histological subtypes.

PMID- 25564179
TI  - Clinical pharmacy intervention post tonsillectomy: a randomized control trial.
AB  - BACKGROUND: Pain control in pediatric patients undergoing tonsillectomy remains a
      dilemma. Tramadol and ketamine are reported to be an effective analgesic. AIM OF
      THE STUDY: To evaluate the effect of peritonsillar infiltration of tramadol in
      combination with ketamine versus peritonsillar infiltration of tramadol
      posttonsillectomy. SETTING: Specialty hospital in Jordan. METHOD: Sixty children,
      aged 7-12 years, selected for tonsillectomy were enrolled in the study. We
      divided the patients into two groups 30 of each, Group I: received peritonsillar
      saline and peritonsillar infiltration of tramadol 2 mg/kg, Group II: received
      peritonsillar infiltration of ketamine 1.0 mg/kg added to peritonsillar tramadol
      2 mg/kg. MAIN OUTCOME MEASURE: Hemodynamic stability, pain scale, first request
      of analgesia, total analgesics consumption and post-operative nausea and vomiting
      (PONV) side effects were recorded 24 h after surgery. RESULTS: The analysis of
      data showed that Group II had significantly lower face pain scale, longer time
      for first request of analgesia, and better hemodynamic stability than GI (p <
      0.001). On the other hand the total analgesics requirements, time of surgery, and
      PONV showed no significant differences between the two groups. CONCLUSION:
      Combined use of peritonsillar infiltration of ketamine 1.0 mg/kg with tramadol 2
      mg/kg provided prolong analgesic effects, less pain with no side effect, and
      better hemodynamic stability compared with using tramadol alone in patients
      undergoing tonsillectomy.

PMID- 25564180
TI  - A detailed analysis of online pharmacy characteristics to inform safe usage by
      patients.
AB  - BACKGROUND: Evidence suggests that consumers potentially put themselves at risk
      when purchasing medicines on-line. Whilst logos provided by regulators may
      provide some level of reassurance there may be other indicators which could be
      used by consumers to identify those websites which may be safely used.
      OBJECTIVES: Identify characteristics of on-line pharmacies which are related to
      whether websites are regulated or non-regulated and those characteristics which
      could be used by patients to increase the likelihood of accessing regulated
      sites. SETTING: Online pharmacies which supply diazepam, fluoxetine and
      simvastatin. METHODS: Using piloted search terms via Google and Yahoo search
      engines, identified websites were screened for regulatory status, adherence to
      regulatory standards, administrative requirements, clinical assessment
      requirements and additional details deemed to be of relevance to a user.
      Characteristics of regulated and non-regulated (defined as those with an absence
      of a correctly linked regulatory logo) websites were compared to identify
      differences which could be used to improve patient safety. MAIN OUTCOME MEASURE:
      Regulatory status, adherence to regulatory standards, quality of information
      provision, barriers to medicines access. RESULTS: 113 websites sold diazepam,
      fluoxetine and simvastatin; were identified within the first 100 results. Less
      than quarter were found to be regulated online pharmacies. 80 websites were
      willing to sell the medication without a prescription. The unregulated internet
      pharmacy websites (defined as those with an absence of a correctly linked
      regulatory logo) were found to adhere more closely to the clinical criteria, were
      less significantly likely to disclose a contact name and address, telephone
      number of the pharmacy or demand a prescription prior to sale (P < 0.05, Fisher's
      Exact). CONCLUSIONS: The three prescription-only medicines which are liable to
      abuse, have potentially serious interactions and require counselling to ensure
      patient safety are readily available via the internet. When purchasing medicines
      via this route UK consumers should be made aware of the importance of regulatory
      logos and additionally should ensure that the seller can be meaningfully
      contacted by the contact details provided. The provision of clinical information
      should not be used alone as an indication of the seller's provenance.

PMID- 25564181
TI  - Automatic messaging for improving patients engagement in diabetes management: an
      exploratory study.
AB  - Mobile health systems aiming to promote adherence may cost-effectively improve
      the self-management of chronic diseases like diabetes, enhancing the compliance
      to the medical prescription, encouraging and stimulating patients to adopt
      healthy life styles and promoting empowerment. This paper presents a strategy for
      m-health applications in diabetes self-management that is based on automatic
      generation of feedback messages. A feedback assistant, representing the core of
      architecture, delivers dynamic and automatically updated text messages set up on
      clinical guideline and patient's lifestyle. Based on this strategy, an m-health
      adherence system was designed, developed and tested in a small-scale exploratory
      study with T1DM and T2DM patients. The results indicate that the system could be
      feasible and well accepted and that its usage increased along with adherence to
      prescriptions during the 4 weeks of the study. A more extensive research is
      pending to corroborate these outcomes and to establish a clear benefit of the
      proposed solution. 

PMID- 25564182
TI  - Prediction of protein subcellular localization by incorporating multiobjective
      PSO-based feature subset selection into the general form of Chou's PseAAC.
AB  - In this article, the possible subcellular location of a protein is predicted
      using multiobjective particle swarm optimization-based feature selection
      technique. In general form of pseudo-amino acid composition, the protein
      sequences are used for constructing protein features. Here, the different amino
      acids compositions are used to construct the feature sets. Therefore, the data
      are presented as sample of protein versus amino acid compositions as features.
      The proposed algorithm tries to maximize the feature relevance and minimize the
      feature redundancy simultaneously. After proposed algorithm is executed on the
      multiclass dataset, some features are selected. On this resultant feature subset,
      tenfold cross-validation is applied and corresponding accuracy, F score, entropy,
      representation entropy and average correlation are calculated. The performance of
      the proposed method is compared with that of its single objective versions,
      sequential forward search, sequential backward search, minimum redundancy maximum
      relevance with two schemes, CFS, CBFS, [Formula: see text], Fisher discriminant
      and a Cluster-based technique. 

PMID- 25564183
TI  - Efficient detection of wound-bed and peripheral skin with statistical colour
      models.
AB  - A pressure ulcer is a clinical pathology of localised damage to the skin and
      underlying tissue caused by pressure, shear or friction. Reliable diagnosis
      supported by precise wound evaluation is crucial in order to success on treatment
      decisions. This paper presents a computer-vision approach to wound-area detection
      based on statistical colour models. Starting with a training set consisting of
      113 real wound images, colour histogram models are created for four different
      tissue types. Back-projections of colour pixels on those histogram models are
      used, from a Bayesian perspective, to get an estimate of the posterior
      probability of a pixel to belong to any of those tissue classes. Performance
      measures obtained from contingency tables based on a gold standard of segmented
      images supplied by experts have been used for model selection. The resulting
      fitted model has been validated on a training set consisting of 322 wound images
      manually segmented and labelled by expert clinicians. The final fitted
      segmentation model shows robustness and gives high mean performance rates [(AUC:
      .9426 (SD .0563); accuracy: .8777 (SD .0799); F-score: 0.7389 (SD .1550); Cohen's
      kappa: .6585 (SD .1787)] when segmenting significant wound areas that include
      healing tissues. 

PMID- 25564184
TI  - A global health elective for US medical students: the 35 year experience of the
      State University of New York, Downstate Medical Center, School of Public Health.
AB  - The School of Public Health at the State University of New York, Downstate
      Medical Center has sponsored a 6-8 week global health elective for fourth year
      medical students since 1980. The purpose of this elective is to provide students
      with an opportunity to observe the health care and public health delivery systems
      in low-income countries, provide medical service and have a cross-cultural
      experience. Over the course of the past 35 years, 388 students have participated
      in this global health elective in more than 41 low-income countries. The most
      popular sites include the Dominican Republic, Guatemala, India, Kenya and
      Thailand. Overall, interest in this elective has persisted throughout the course
      of time, sometimes temporarily increasing or decreasing with outside factors,
      such as the events of 11 September 2001 and the outbreak of Severe Acute
      Respiratory Syndrome in Asia. Recent annual applications for this elective have
      been as high as 44 out of a class of 200 students. Over the past 10 years, annual
      acceptance rates have varied, ranging from a low of 32 % in 2007-2008 to a high
      of 74 % in 2010-2011 and 2013-2014. Careful screening, including a written
      application, review of academic records and personal interviews has resulted in
      the selection of highly mature, adaptable and dedicated students who have
      performed well at overseas sites. Student rated satisfaction levels with this
      elective are almost universally high, with most rating it the best experience of
      their medical school years. Students undergo extensive preparation prior to their
      travel overseas, including a review of individual health and safety issues,
      travel and lodging, and the nature of the host country culture, health care
      system and assignment site. Downstate medical students are especially experienced
      in cross-cultural understanding because of the unusual diversity of the patient
      population in Brooklyn, and the diversity of local hospital staff and the medical
      school class. The Alumni Fund of the College of Medicine has steadfastly
      supported this elective with both a philosophical commitment and financial grants
      to help defray costs since the very early years. The Dr. Michael and Lona B.
      Kenney Endowment, the Joshua H. Weiner endowment, and the LSK Foundation have
      also provided financial support for this elective. Throughout the course of this
      elective, overseas preceptors have willingly given of their time and
      institutional resources to make these experiences available and meaningful for
      our students.

PMID- 25564185
TI  - Introduction and overview to issue on new developments in pediatric
      hematology/oncology.

PMID- 25564187
TI  - Medial epicondyle fractures in children.
AB  - PURPOSE OF REVIEW: The present review discusses the relevant anatomy, clinical
      presentation, and management of medial epicondyle fractures, including diagnostic
      controversies, the indications for operative and nonoperative management, and
      outcomes. RECENT FINDINGS: Recent studies have highlighted the underestimation of
      fracture displacement seen on typical radiographic views and have attempted to
      define the location of the medial epicondyle on radiographs to improve the
      accuracy of measuring displacement. They have demonstrated variable outcomes
      following open reduction and internal fixation of medial epicondyle fractures
      that are associated with intra-articular incarceration. Newer evidence supports
      the fixation of medial epicondyle fractures in adolescent athletes, to allow
      return to competitive sports. SUMMARY: Medial epicondyle fractures of the distal
      humerus account for 12% of pediatric elbow fractures and are frequently
      associated with intra-articular incarceration of the fracture fragment, elbow
      dislocation, ulnar nerve injury, and other upper extremity fractures. Recent
      literature calls into question the accuracy of measuring fracture displacement,
      and controversy exists regarding optimal management of these fractures. Good
      outcomes have been achieved with nonoperative treatment for minimally displaced
      fractures, despite a high rate of nonunion. In patients with displaced fractures,
      fixation yields stability, functional range of motion, and the ability to return
      to previous activity levels, including sports. Complications include stiffness,
      instability, deformity, superficial wound infections, and symptomatic nonunion.
      Further study is required to standardize the measurement of displacement and to
      clarify indications for operative treatment in both sedentary and active
      children.

PMID- 25564186
TI  - New developments in pediatric venous thromboembolism and anticoagulation,
      including the target-specific oral anticoagulants.
AB  - PURPOSE OF REVIEW: Pediatric venous thromboembolism (VTE) can affect children of
      all ages, requiring considerable pharmacologic intervention and is often
      associated with significant morbidity. Current research efforts are directed
      toward the development of risk-stratified VTE prevention strategies employing
      pharmacologic thromboprophylaxis, the optimization of conventional
      anticoagulation, and the investigation of the safety and efficacy of target
      specific oral anticoagulants (TSOACs) in children. RECENT FINDINGS: Recent
      research has considerably improved the understanding of risk factors of hospital
      acquired VTE and how these factors may be employed in risk-stratified paradigms
      for VTE prevention in children. Additional insight has been gained in the
      optimization of conventional anticoagulants in special populations such as
      neonates and children with inflammatory conditions, and in improving the overall
      safety and compliance with periprocedural anticoagulation and the use of home
      International Normalized Ratio monitoring. Furthermore, the use of TSOACs has
      been described in children and is the focus of numerous ongoing clinical trials
      that are evaluating the safety and efficacy of these agents in children with VTE.
      SUMMARY: Identification of hospital-acquired VTE risk factors may inform
      pediatric VTE prevention strategies. Although initial use of TSOACs may be
      promising, investigation of safety and efficacy in children is still underway.

PMID- 25564188
TI  - Surgical options for anterior cruciate ligament reconstruction in the young
      child.
AB  - PURPOSE OF REVIEW: To review the most recent literature on the epidemiology,
      diagnosis, treatment, and outcomes of pediatric anterior cruciate ligament
      injury. RECENT FINDINGS: There is an increasing prevalence of anterior cruciate
      ligament injuries in pediatric and adolescent athletes, and nonoperative
      management of these injuries results in worse outcomes than surgical
      reconstruction. Prevention exercise protocols are cost-effective in preventing
      this injury in adolescent athletes. A number of techniques are currently in
      practice that address anterior cruciate ligament injuries in the skeletally
      immature, but there is no consensus on the optimal technique. SUMMARY: The
      reported clinical outcomes from anterior cruciate ligament reconstruction in
      young patients are favorable.

PMID- 25564189
TI  - Important determinants of newborn health: postpartum depression, teen parenting,
      and breast-feeding.
AB  - PURPOSE OF REVIEW: The present article addresses recent research related to three
      important determinants of newborn health: postpartum depression, teenage parents
      and their offspring, and breast-feeding. RECENT FINDINGS: Postpartum depression
      can impact the entire family unit, and fathers may be affected more than
      previously recognized. Teenage mothers and their infants are at risk of a number
      of poor physical and mental health outcomes. New research continues to support
      the benefits of breast-feeding infants, and hospitals have adopted policies to
      improve breast-feeding rates. SUMMARY: Recognizing both maternal and paternal
      depression during outpatient visits is key to family well-being, as well as to
      infant development and attachment. Pediatric providers should address the unique
      emotional, socioeconomic, educational, and health needs of teen mothers. Hospital
      implementation of evidence-based policies may increase the number of mothers who
      are successful in establishing breast-feeding, and pediatric healthcare providers
      should be prepared to support mothers of breast-feeding infants.

PMID- 25564191
TI  - Atypical features and treatment choices in bipolar disorders: a result of the
      National Bipolar Mania Pathway Survey in China.
AB  - In this study, we examined the point prevalence rate of atypical features in
      bipolar disorder, and estimated the potential impact of these features on
      treatment practices in China. Using the atypical features criteria of the
      Diagnostic and Statistical Manual of the American Psychiatric Association (DSM
      IV), we documented the atypical symptoms in 3 906 consecutive participants with
      bipolar disorder enrolled at 26 psychiatric services across China. We further
      assessed the association between atypical features and the treatment approaches,
      including the prescription of antidepressants. The overall point prevalence rate
      of atypical features was 9.1% among patients with various bipolar disorder
      subtypes. When the definition was broadened to include atypical features B, the
      overall rate increased to 11.8%. Interestingly, among patients with the mixed
      state and remission subtypes, there was a significant difference in the rates of
      antidepressant medication usage between patients who met and those who did not
      meet the criteria for atypical features B. These findings indicate a trend of
      using antidepressants for these two types of patients with atypical features.
      Further, for both mixed state and remission patients, treatment approaches were
      related to atypical features B. Our findings provide evidence to assist
      clinicians to readily recognize atypical features in bipolar subtypes and can
      propose treatments based on these diagnoses. 

PMID- 25564192
TI  - Altered functional connectivity networks of hippocampal subregions in remitted
      late-onset depression: a longitudinal resting-state study.
AB  - The regional specificity of hippocampal abnormalities in late-life depression
      (LLD) has been demonstrated in previous studies. In this study, we sought to
      examine the functional connectivity (FC) patterns of hippocampal subregions in
      remitted late-onset depression (rLOD), a special subtype of LLD. Fourteen rLOD
      patients and 18 healthy controls underwent clinical and cognitive evaluations as
      well as resting-state functional magnetic resonance imaging scans at baseline and
      at ~21 months of follow-up. Each hippocampus was divided into three parts, the
      cornu ammonis (CA), the dentate gyrus, and the subicular complex, and then six
      seed-based hippocampal subregional networks were established. Longitudinal
      changes of the six networks over time were directly compared between the rLOD and
      control groups. From baseline to follow-up, the rLOD group showed a greater
      decline in connectivity of the left CA to the bilateral posterior cingulate
      cortex/precuneus (PCC/PCUN), but showed increased connectivity of the right
      hippocampal subregional networks with the frontal cortex (bilateral medial
      prefrontal cortex/anterior cingulate cortex and supplementary motor area).
      Further correlative analyses revealed that the longitudinal changes in FC between
      the left CA and PCC/PCUN were positively correlated with longitudinal changes in
      the Symbol Digit Modalities Test (r = 0.624, P = 0.017) and the Digit Span Test
      (r = 0.545, P = 0.044) scores in the rLOD group. These results may provide
      insights into the neurobiological mechanism underlying the cognitive dysfunction
      in rLOD patients. 

PMID- 25564194
TI  - Effcacy of Williams LifeSkills Training in improving psychological health of
      Chinese male juvenile violent offenders: a randomized controlled study.
AB  - This randomized controlled study was conducted to evaluate the efficacy of
      Williams LifeSkills Training (WLST) as a means of improving the psychological
      health of Chinese male juvenile violent offenders. Sixty-six participants were
      assigned randomly to receive the usual intervention plus 8 weeks of WLST (study
      group, n = 33) or only the usual intervention (control group, n = 33). We found
      that the study group exhibited significantly decreased State-Trait Anxiety
      Inventory (STAI X-1, X-2) STAX2 scores and Trait Coping Style Questionnaire
      (TCSQ) negative scores, and increased Interpersonal Support Evaluation List
      (ISEL) tangible scores from baseline to 9 weeks later (P <0.01). In addition, a
      between-group difference in changes of TCSQ negative score was observed at the
      end of week 9 (P <0.05). These fndings suggest that WLST can improve trait
      anxiety, coping style, and interpersonal support in male Chinese juvenile violent
      offenders. 

PMID- 25564193
TI  - Morphological changes in gray matter volume correlate with catechol-O-methyl
      transferase gene Val158Met polymorphism in first-episode treatment-naive patients
      with schizophrenia.
AB  - The catechol-O-methyltransferase (COMT) gene is a schizophrenia susceptibility
      gene. A common functional polymorphism of this gene, Val158/158Met, has been
      proposed to influence gray matter volume (GMV). However, the effects of this
      polymorphism on cortical thickness/surface area in schizophrenic patients are
      less clear. In this study, we explored the relationship between the Val158Met
      polymorphism of the COMT gene and the GMV/cortical thickness/cortical surface
      area in 150 first-episode treatment-naive patients with schizophrenia and 100
      healthy controls. Main effects of diagnosis were found for GMV in the cerebellum
      and the visual, medial temporal, parietal, and middle frontal cortex. Patients
      with schizophrenia showed reduced GMVs in these regions. And main effects of
      genotype were detected for GMV in the left superior frontal gyrus. Moreover, a
      diagnosis * genotype interaction was found for the GMV of the left precuneus, and
      the effect of the COMT gene on GMV was due mainly to cortical thickness rather
      than cortical surface area. In addition, a pattern of increased GMV in the
      precuneus with increasing Met dose found in healthy controls was lost in patients
      with schizophrenia. These findings suggest that the COMTMet variant is associated
      with the disruption of dopaminergic influence on gray matter in schizophrenia,
      and the effect of the COMT gene on GMV in schizophrenia is mainly due to changes
      in cortical thickness rather than in cortical surface area. 

PMID- 25564195
TI  - The management of the painful bipartite patella: a systematic review.
AB  - PURPOSE: This study aimed to identify the most effective method for the treatment
      of the symptomatic bipartite patella. METHODS: A systematic review of the
      literature was completed, and all studies assessing the management of a bipartite
      patella were included. Owing to the paucity of randomised controlled trials, a
      narrative review of 22 studies was completed. A range of treatments were
      assessed: conservative measures, open and arthroscopic fixation or excision and
      soft tissue release and excision. RESULTS: All of the methods provided results
      ranging from good to excellent, with acceptable complication rates. CONCLUSIONS:
      This is a poorly answered treatment question. No firm guidance can be given as to
      the most appropriate method of treating the symptomatic bipartite patella. This
      study suggests that there are a number of effective treatments with acceptable
      complication rates and it may be that treatments that conserve the patella are
      more appropriate for larger fragments. LEVEL OF EVIDENCE: IV.

PMID- 25564197
TI  - Real-time ultrasound guidance for ventricular catheter placement in pediatric
      cerebrospinal fluid shunts.
AB  - PURPOSE: Cerebrospinal fluid shunt failure is related to additional morbidity.
      Misplacement of ventricular catheters occurs in 40 % with freehand technique and
      is a risk factor for shunt failure. The goal of this study was to analyze the
      impact of intraoperative real-time ultrasound on catheter positioning and outcome
      in children. METHODS: We compared children receiving ultrasound-guided procedures
      to matched historical freehand controls. Burr hole and convex probes were used
      (ProSound Alpha 6, Hitachi Aloka Medical Ltd., Tokyo, Japan). Catheter position
      was graded as grade I (optimal), II (contralateral ventricle or contact with
      ventricular structures), or III (misplacement). Correlation analysis was
      performed to identify determinants of outcome. RESULTS: The study group (n = 17)
      was balanced with the control group (n = 14) for variables such as mean age (4.7
      vs 4.3 years) and preoperative frontal occipital horn ratio (FOHR; 0.45 vs 0.43).
      In the study group, grade I catheter position was achieved in 6 (35%) and grade
      II in 11 patients (65%), compared to 2 (18%) and 3 patients (27%) in the control
      group. While no grade III position occurred in the study group, it was found in
      nine control patients (43%) (P = 0.0029). Failure rate was highest in grade III
      (83%) compared to grade I catheters (50%). CONCLUSIONS: This analysis
      demonstrated an improvement of catheter positioning with ultrasound guidance. In
      the absence of additional burden or risks, this method should be favored over
      freehand technique. It remains to be demonstrated in a randomized controlled
      fashion to what extent improved catheter position translates into improved
      outcome.

PMID- 25564196
TI  - Methylprednisolone reduces pain and decreases knee swelling in the first 24 h
      after fast-track unicompartmental knee arthroplasty.
AB  - PURPOSE: Unicompartmental knee arthroplasty (UKA) results in less operative
      trauma and faster patient recovery than after a conventional total knee
      arthroplasty. Despite an increased focus on multimodal analgesic strategies,
      there is still a substantial level of patient-reported pain in the early
      postsurgical period after UKA. The purpose of the study was to evaluate the
      effect of a single preoperative dose of systemic methylprednisolone on
      postsurgical pain after fast-track UKA. METHODS: Seventy-two patients in two
      consecutive series undergoing unilateral UKA were included in a prospective
      cohort study. The patients (n = 35) in the treatment group received a single
      preoperative dose of systemic methylprednisolone 125 mg, whereas the control
      group (n = 37) did not. Outcome measures were postsurgical pain at rest and
      during walking, consumption of opioids for pain rescue, knee swelling and knee
      range of motion, and complications. RESULTS: In the first 24 h after surgery, the
      treatment group had less pain at rest (p < 0.001) and during walking (p < 0.001)
      and less consumption of opioids (p = 0.01) in comparison with the control group.
      Furthermore, the treatment group had 2.2 cm less knee swelling (p = 0.02) in the
      first post-operative day, and better knee extension (p = 0.004), whereas knee
      flexion was similar (n.s.) between groups. No serious complications were
      associated with the treatment. CONCLUSION: Addition of a single preoperative dose
      of 125 mg systemic methylprednisolone to a multimodal analgesic regime
      significantly reduced postsurgical pain and opioid consumption and decreased knee
      swelling in the first 24 h after fast-track UKA. LEVEL OF EVIDENCE: Therapeutic
      study, Level II.

PMID- 25564200
TI  - The impact of pharmaceutical innovation on premature mortality, cancer mortality,
      and hospitalization in Slovenia, 1997-2010.
AB  - BACKGROUND: In Slovenia during the period 2000-2010, the number of years of
      potential life lost before the age of 70 years per 100,000 population under 70
      years of age declined 25 %. OBJECTIVE: The aim of this study was to test the
      hypothesis that pharmaceutical innovation played a key role in reducing premature
      mortality from all diseases in Slovenia, and to examine the effects of
      pharmaceutical innovation on the age-standardized number of cancer deaths and on
      hospitalization from all diseases. Estimates and other data were used to
      calculate the incremental cost effectiveness of pharmaceutical innovation in
      Slovenia. METHOD: Longitudinal disease-level data was analyzed to determine
      whether diseases for which there was greater pharmaceutical innovation-a larger
      increase in the number of new chemical entities (NCEs) previously launched-had
      larger declines in premature mortality, the age-standardized number of cancer
      deaths, and the number of hospital discharges. My methodology controls for the
      effects of macroeconomic trends and overall changes in the healthcare system.
      RESULTS: Premature mortality from a disease is inversely related to the number of
      NCEs launched more than 5 years earlier. On average, the introduction of an
      additional NCE for a disease reduced premature mortality from the disease by 2.4
      % 7 years later. The age-standardized number of cancer deaths is inversely
      related to the number of NCEs launched 1-6 years earlier, conditional on the age
      standardized number of new cancer cases diagnosed 0-2 years earlier. On average,
      the launch of an NCE reduced the number of hospital discharges 1 year later by
      approximately 1.5 %. CONCLUSIONS: The estimates imply that approximately two
      thirds of the 2000-2010 decline in premature mortality was due to pharmaceutical
      innovation. If no NCEs had been launched in Slovenia during 1992-2003, the age
      standardized number of cancer deaths in 2008 would have been 12.2 % higher. The
      NCEs launched in Slovenia during 2003-2009 are estimated to have reduced the
      number of hospital discharges in 2010 by 7 %. If we assume that pharmaceutical
      expenditure was the only type of expenditure affected by pharmaceutical
      innovation, the cost per life-year saved was <euro>3,953, which is well below
      even the lowest estimates of the value of a life-year saved. Moreover, 85 % of
      the increase in drug expenditure may have been offset by a reduction in hospital
      expenditure; therefore. the cost per life-year saved may have been only ?611.

PMID- 25564198
TI  - Inhibition of Wnt/beta-catenin signal is alleviated reactive gliosis in rats with
      hydrocephalus.
AB  - BACKGROUND: Reactive gliosis has been implicated in the pathogenesis of
      communicating hydrocephalus. Because the activation of Wnt/beta-catenin signaling
      pathway is considered as a significant factor to contribute to brain development,
      neurodegenerative process, and reactive gliosis, we target this pathway for
      intervention by using sFRP-l and investigated the expression of beta-catenin,
      cyclin D-1, and glial fibrillary acidic protein (GFAP) in the brain of
      experimental hydrocephalic rats in terms of protein and gene expression. METHODS:
      Therefore, 30 adult SD rats were randomly divided into the normal group (n = 5),
      the sham operation group (n = 5), the hydrocephalus group (n = 10), and the sFRP
      l group (n = 10). Hydrocephalic rat models were induced by intraventricular
      injections of 3% kaolin while sFRP-l group was treated by sFRP-l with kaolin
      injections. The ventricular dilatation was examinated by MRI at 2-week post
      operation. After that, beta-catenin, cyclin D-1, and GFAP were qualified by
      Western blot and immunohistochemistry. RESULTS: According to the result, the
      expression of beta-catenin and cyclin D-1 increased (P < 0. 05) in the brain
      tissue of the hydrocephalus group compared with that of the sham group, while
      GFAP expression in the hydrocephalus group is more obvious (P < 0. 05). In the
      sFRP-l group, the expression of beta-catenin and cyclin D-1 and GFAP expression
      is lower (P < 0. 05) compared with those of the hydrocephalus group. We
      demonstrated that the Wnt/beta-catenin pathway is activated in the experimental
      hydrocephalic rat brain. sFRP-l inhibited the expression of beta-catenin and
      cyclin D-1 and alleviated reactive gliosis in the hydrocephalic rat brain tissue,
      while the development of hydrocephalus was delayed. CONCLUSION: These results
      suggest that regulating Wnt/beta-catenin signaling pathway may provide new
      therapeutic methods for hydrocephalic patients.

PMID- 25564201
TI  - The breast cancer immunophenotype of TP53-p.R337H carriers is different from that
      observed among other pathogenic TP53 mutation carriers.
AB  - Germline TP53 mutations are associated with Li-Fraumeni syndrome, an autosomal
      dominant disorder characterized by a predisposition to multiple early-onset
      cancers including breast cancer (BC), the most prevalent tumor among women. The
      majority of germline TP53 mutations are clustered within the DNA-binding domain
      of the gene, disrupting the structure and function of the protein. A specific
      germline mutation in the tetramerization domain of p53, p.R337H, was reported at
      a high frequency in Southern and Southeastern Brazil. This mutation appears to
      result in a more subtle defect in the protein, which becomes functionally
      deficient only under particular conditions. Recent studies show that the BC
      phenotype in TP53 mutation carriers is often HER2 positive (63-83%). Considering
      that the immunophenotype of BC among p.R337H carriers has not been reported, we
      reviewed immunohistochemistry data of 66 p.R337H carriers in comparison with 12
      patients with other non-functional TP53 germline mutation. Although 75% of
      carriers of these mutations showed significant HER2 overexpression (3+),
      corroborating previous studies, only 22.7% of p.R337H patients had BC
      overexpressing HER2. These results reinforce the notion that different germline
      mutations in TP53 may predispose to BC via different mechanisms.

PMID- 25564203
TI  - Improvement of ansamitocin P-3 production by Actinosynnema mirum with fructose as
      the sole carbon source.
AB  - Ansamitocin P-3 (AP-3) is an active and potent anti-tumor maytansinoid, which is
      usually produced by Actinosynnema spp. In this study, the effects of different
      carbon sources on biomass and AP-3 production by Actinosynnema mirum were
      investigated. The results showed great biomass production behavior of A. mirum in
      glucose medium comparatively to other carbon sources. Interestingly, when
      fructose was used as the sole carbon source, the highest yield of AP-3 was
      obtained, which was about fourfold than that of strain cultured in glucose after
      168 h. Further analysis conducted in regard to better understanding of such
      observations in glucose and fructose defined media showed that fructose improves
      AP-3 production through the stimulation of the key genes of the secondary
      metabolism pathways. It was concluded that fructose could be a potential carbon
      source for cost-effective production of AP-3 from an industrial point of view. 

PMID- 25564204
TI  - Impact of enzyme loading on the efficacy and recovery of cellulolytic enzymes
      immobilized on enzymogel nanoparticles.
AB  - Cellulase and beta-glucosidase were adsorbed on a polyacrylic acid polymer brush
      grafted on silica nanoparticles to produce enzymogels as a form of enzyme
      immobilization. Enzyme loading on the enzymogels was increased to a saturation
      level of approximately 110 MUg (protein) mg(-1) (particle) for each enzyme.
      Enzymogels with varied enzyme loadings were then used to determine the impact on
      hydrolysis rate and enzyme recovery. Soluble sugar concentrations during the
      hydrolysis of filter paper and Solka-Floc with the enzymogels were 45 and 53%,
      respectively, of concentrations when using free cellulase. beta-Glucosidase
      enzymogels showed lower performance; hydrolyzate glucose concentrations were just
      38% of those using free enzymes. Increasing enzyme loading on the enzymogels did
      not reduce net efficacy for cellulase and improved efficacy for beta-glucosidase.
      The use of free cellulases and cellulase enzymogels resulted in hydrolyzates with
      different proportions of cellobiose and glucose, suggesting differential
      attachment or efficacy of endoglucanases, exoglucanases, and beta-glucosidases
      present in cellulase mixtures. When loading beta-glucosidase individually, higher
      enzyme loadings on the enzymogels produced higher hydrolyzate glucose
      concentrations. Approximately 96% of cellulase and 66 % of beta-glucosidase were
      recovered on the enzymogels, while enzyme loading level did not impact recovery
      for either enzyme.

PMID- 25564205
TI  - Optimization of three operating parameters for a two-step fed sequencing batch
      reactor (SBR) system to remove nutrients from swine wastewater.
AB  - In this study, the effect of three operating parameters, i.e., the first/second
      volumetric feeding ratio (milliliters/milliliters), the first anaerobic/aerobic
      (an/oxic) time ratio (minute/minute), and the second an/oxic time ratio
      (minute/minute), on the performance of a two-step fed sequencing batch reactor
      (SBR) system to treat swine wastewater for nutrients removal was examined.
      Central Composite Design, coupled with Response Surface Methodology, was employed
      to test these parameters at five levels in order to optimize the SBR to achieve
      the best removal efficiencies for six response variables including total nitrogen
      (TN), ammonium nitrogen (NH4-N), total phosphorus (TP), dissolved phosphorus
      (DP), chemical oxygen demand (COD), and biochemical oxygen demand (BOD). The
      results showed that the three parameters investigated had significant impact on
      all the response variables (TN, NH4-N, TP, DP, COD, and BOD), although the
      highest removal efficiency for each individual responses was associated with
      different combination of the three parameters. The maximum TN, NH4-N, TP, DP,
      COD, and BOD removal efficiencies of 96.38%, 95.38%, 93.62%, 94.3%, 95.26%, and
      92.84% were obtained at the optimal first/second volumetric feeding ratio, first
      an/oxic time ratio, and second an/oxic time ratio of 3.23, 0.4, and 0.8 for TN;
      2.64, 0.72, and 0.76 for NH4-N; 3.08, 1.16, and 1.07 for TP; 1.32, 0.81, and 1.0
      for DP; 2.57, 0.96, and 1.12 for COD; and 1.62, 0.64, and 1.61 for BOD,
      respectively. Good linear relationships between the predicted and observed
      results for all the response variables were observed.

PMID- 25564202
TI  - Rhipicephalus microplus serine protease inhibitor family: annotation, expression
      and functional characterisation assessment.
AB  - BACKGROUND: Rhipicephalus (Boophilus) microplus evades the host's haemostatic
      system through a complex protein array secreted into tick saliva. Serine protease
      inhibitors (serpins) conform an important component of saliva which are
      represented by a large protease inhibitor family in Ixodidae. These secreted and
      non-secreted inhibitors modulate diverse and essential proteases involved in
      different physiological processes. METHODS: The identification of R. microplus
      serpin sequences was performed through a web-based bioinformatics environment
      called Yabi. The database search was conducted on BmiGi V1, BmiGi V2.1, five SSH
      libraries, Australian tick transcriptome libraries and RmiTR V1 using
      bioinformatics methods. Semi quantitative PCR was carried out using different
      adult tissues and tick development stages. The cDNA of four identified R.
      microplus serpins were cloned and expressed in Pichia pastoris in order to
      determine biological targets of these serpins utilising protease inhibition
      assays. RESULTS: A total of four out of twenty-two serpins identified in our
      analysis are new R. microplus serpins which were named as RmS-19 to RmS-22. The
      analyses of DNA and predicted amino acid sequences showed high conservation of
      the R. microplus serpin sequences. The expression data suggested ubiquitous
      expression of RmS except for RmS-6 and RmS-14 that were expressed only in nymphs
      and adult female ovaries, respectively. RmS-19, and -20 were expressed in all
      tissues samples analysed showing their important role in both parasitic and non
      parasitic stages of R. microplus development. RmS-21 was not detected in ovaries
      and RmS-22 was not identified in ovary and nymph samples but were expressed in
      the rest of the samples analysed. A total of four expressed recombinant serpins
      showed protease specific inhibition for Chymotrypsin (RmS-1 and RmS-6),
      Chymotrypsin / Elastase (RmS-3) and Thrombin (RmS-15). CONCLUSION: This study
      constitutes an important contribution and improvement to the knowledge about the
      physiologic role of R. microplus serpins during the host-tick interaction.

PMID- 25564206
TI  - Purification and characterization of a GH11 xylanase from biobutanol-producing
      Clostridium beijerinckii G117.
AB  - Most biobutanol-producing Clostridium strains are unable to ferment
      polysaccharides such as cellulose and xylan due to the lack of hydrolyzing
      enzymes. In this study, we show that Clostridium beijerinckii G117, a newly
      isolated biobutanol-producing strain, expresses xylanase enzyme in the presence
      of 1% beechwood xylan. The xylanase activity in the medium containing actively
      growing culture and 1% of beechwood xylan can reach up to 2.66 U/ml after 14 h of
      fermentation. Using salting-out and size-exclusion chromatography, we purify the
      crude xylanase by 8.7-fold from the supernatant with a yield of 32.2%. This
      purified xylanase has a molecular weight of 22.6 kDa, making it one of the
      smallest reported clostridial xylanases. Conserved domain analysis reveals that
      the xylanase belongs to glycoside hydrolase family 11 (GH11) but lacks a
      carbohydrate binding domain. When beechwood xylan is used as substrate for the
      xylanase, majority of the products are xylo-oligosaccharide (~98%), suggesting
      that this is an endo-1,4-beta-xylanase.

PMID- 25564207
TI  - Evaluating a community-partnered cancer clinical trials pilot intervention with
      African American communities.
AB  - Cancer clinical trial (CCT) accrual and retention rates remain disproportionately
      low among African Americans. Awarenesss and access to trials are crucial
      facilitators of trial participation. Strategies developed within a community
      based participatory framework (CBPR) are potential solutions to increase
      awareness and access to CCTs. In this study, we describe the pilot phase of three
      innovative community-centered modules to improve basic CCT knowledge, awareness
      of locations to access CCT information, and opportunities to participate in CCTs.
      Four community organizations completed Community Bridges to CCT training-of-the
      trainer and recruited adult African American volunteers to participate in one of
      three CCT education modules: a workshop about CCTs, a role play describing one
      person's experience with CCTs, or a call and response session reviewing myths and
      facts about CCTs. Pre- and post-test surveys were collected and analyzed using
      McNemar agreement statistic to evaluate changes in knowledge and attitudes
      regarding trials. Trainers enrolled 125 participants in the call and response (n
      = 22), role play (n = 60), and workshop (n = 43) modules. Module participants
      were mostly African American, female, and with a mean age of 53 years. Comparison
      of pre- and post-test responses demonstrates favorable changes in awareness of
      CCTs and where to access CCTs across the sample. Analysis by module type
      indicates significant increases for participants in the call and response (p <
      0.01) and role play modules (p < 0.001), but not the workshop module. Despite
      measures taken to increase the participation and retention rate of African
      Americans in clinical trials, little advancement has been made. Developing
      tailored community education modules on CCTs within the CBPR framework is a
      promising innovation to increase knowledge about CCTs and favorable attitudes
      about participation that are known precursors to trial enrollment. 

PMID- 25564209
TI  - Influence of visceral pleural invasion on survival in completely resected non
      small-cell lung cancer.
AB  - OBJECTIVES: Although the prognostic implications of visceral pleural invasion
      (VPI) are well established, it remains controversial whether the extent of VPI
      affects survival in patients with completely resected non-small-cell lung cancer
      (NSCLC). In addition, the impact of VPI according to nodal status is unclear. We
      evaluated the influence of the extent of pleural invasion on survival by
      analysing a multicentre retrospective database of patients who had undergone
      surgery for NSCLC. METHODS: We retrospectively reviewed the clinicopathological
      characteristics and outcomes of 639 patients with NSCLC who underwent anatomic
      complete resection from 2005 to 2007 at nine hospitals affiliated with the
      Yokohama Consortium of Thoracic Surgeons. RESULTS: The median follow-up was 65.0
      months. The extent of pleural invasion was PL0 in 462 patients, PL1 in 135 and
      PL2 in 42. The 5-year overall survival rate was significantly higher in patients
      with PL0 tumours (75.9%) than in those with PL1 (63.6%) or PL2 tumours (54.1%).
      On subgroup analysis according to nodal status, PL0 was associated with a higher
      survival rate than that of PL1 or PL2 tumours in patients with N0 or N1
      metastasis, but not in those with N2 metastasis. There was no difference between
      PL1 and PL2 in any subgroup. CONCLUSIONS: Our results suggest that the presence
      of VPI, rather than the extent, has an impact on postoperative survival in
      patients with NSCLC who have N0 or N1 metastasis. Because very few previous
      studies have addressed the effects of VPI in patients with N1 disease, further re
      evaluation of the prognostic impact of VPI is necessary in this subgroup of
      patients.

PMID- 25564208
TI  - Salt and osmosensing: role of cytoplasmic hydrogel.
AB  - Osmotic perturbations, occurring frequently under physiological and pathological
      conditions, alter cell size/volume and function. To protect cellular homeostasis,
      cell osmo- and volume-sensing mechanisms activate volume compensatory processes.
      The plasma membrane plays a prominent role in cell volume regulation by mediating
      the selective transport of extra- and intracellular osmolytes. The function of
      the membrane-enclosed cytoplasm in osmosensing and cell volume homeostasis is
      much less appreciated. We present current concepts and discuss evidence of cell
      volume sensors with emphasis on the hydrogel nature of the mammalian cytoplasm
      and its intrinsic osmosensitivity. 

PMID- 25564210
TI  - Improving decision-making regarding oesophagectomy after preoperative therapy.

PMID- 25564211
TI  - RNase1 as a potential mediator of remote ischaemic preconditioning for
      cardioprotection?.
AB  - OBJECTIVES: Remote ischaemic preconditioning (RIPC) is a non-invasive and
      virtually cost-free strategy for protecting the heart against acute ischaemia
      reperfusion injury (IRI). We have recently shown that the inhibition of
      extracellular RNA (eRNA) using non-toxic RNase1 protected the heart against acute
      IRI, reduced myocardial infarct (MI) size and preserved left ventricular systolic
      function in rodent animal MI models. Based on this previous work in animals, the
      role of the eRNA/RNase1 system in cardiac RIPC in humans should be defined.
      METHODS: Fourteen patients underwent cardiac surgery without RIPC; from each
      patient, six separate 5 ml blood specimens from radial artery and two blood
      specimens from coronary sinus at different time points during heart surgery were
      taken. Six healthy donors received RIPC (4 * 5 min upper limb ischaemia); blood
      parameters were quantified before and after RIPC. Twelve patients underwent
      cardiac surgery of which 6 received RIPC, whereas the remaining 6 were exposed to
      sham procedure. Circulating eRNA was quantified in plasma from arterial and
      coronary sinus blood obtained from patients undergoing cardiac by standard
      procedures. Tumour necrosis factor-alpha (TNF-alpha) production by heart tissue
      was assessed by enzyme-linked immuno-sorbent assay; RNase activity was quantified
      by an enzymatic assay. RESULTS: Before surgery, eRNA levels were similar in both
      groups (14 +/- 6 vs 13 +/- 5 ng/ml; P = 0.9967). In patients without RIPC,
      arterial eRNA levels rose during surgery (87 +/- 12 ng/ml) and peaked after (127
      +/- 11 ng/ml) aortic declamping; accordingly, eRNA levels in coronary sinus blood
      were significantly higher (206 +/- 32 ng/ml; P = 0.0129) than that in radial
      artery. Moreover, significant elevation of TNF-alpha (36 +/- 6 ng/ml; P = 0.0059)
      particularly in coronary sinus blood after opening of the aortic clamping was
      observed. Interestingly, applying a RIPC protocol significantly increased levels
      of plasma endogenous vascular RNase1 by >7-fold, and the levels of arterial (31
      +/- 7 ng/ml; P = 0.0024) and coronary sinus (37 +/- 9 ng/ml; P < 0.0001)
      circulating eRNA, as well as circulating TNF-alpha (20 +/- 4 ng/ml; P = 0.0050)
      levels were significantly reduced. CONCLUSIONS: Upon RIPC, the level of
      cardioprotective RNase1 increased, while the concentration of damaging eRNA and
      TNF-alpha decreased. The present findings imply a significant contribution of the
      RIPC-dependent (endothelial) RNase1 for improving the outcome of cardiac surgery.
      However, the exact mechanism of RNase1-induced cardioprotection still remains to
      be explored.

PMID- 25564212
TI  - Longitudinal quantification of radical bursts during pulmonary ischaemia and
      reperfusion.
AB  - OBJECTIVES: Pulmonary ischaemia-reperfusion injury (IRI) is associated with
      several life-threatening pulmonary disorders, and may severely compromise the
      outcome of lung transplantation. Highly reactive molecules such as superoxide,
      nitric oxide (NO) and peroxynitrite (ONOO(-)) are presumed to contribute to IRI
      pathogenesis, but this assumption is based on indirect measurements. We use
      electron spin resonance (ESR) to directly quantify free radical formation after
      pulmonary ischaemia and reperfusion. METHODS: Five groups of 10 Swiss mice were
      subjected to left pulmonary hilum clamping for 1 h of ischaemia followed by 0, 1,
      4 and 24 h of reperfusion or to sham thoracotomy alone as control procedure. In
      five mice per group, ESR was used to measure iron-diethyldithio-carbamate
      trihydrate-trapped NO in the lung. In the other group of 5, reactive oxygen
      species generation in the lung and in blood was quantified with ESR by detection
      of ascorbyl radical and CMH spin probe, respectively. Pulmonary ONOO(-) was
      monitored with nitrotyrosine Western blotting. RESULTS: After 1 h of reperfusion,
      a pulmonary NO peak (14.69 +/- 0.91 * 10(4) Arbitrary Units (A.U.). vs 1.84 +/-
      0.75 * 10(4) A.U. in sham; P < 0.001) coincided with a significant increase in
      nitrosated proteins (0.105 +/- 0.015 A.U.) compared with sham (0.047 +/- 0.006
      A.U.); P < 0.005). Peripheral blood showed a significant free radical burst after
      1 h of ischaemia (11 774 +/- 728 A.U. vs 6660 +/- 833 A.U. in sham; P < 0.001).
      CONCLUSIONS: Longitudinal quantification of free radicals during IRI reveals the
      occurrence of two major radical bursts. The radical peak in peripheral blood
      after ischaemia may be related to systemic hypoxia. After 1 h of reperfusion, the
      lung tissue shows a significant increase of superoxide, NO and their reaction
      products, which are probably involved in IRI pathogenesis.

PMID- 25564213
TI  - Index of prolonged air leak score validation in case of video-assisted
      thoracoscopic surgery anatomical lung resection: results of a nationwide study
      based on the French national thoracic database, EPITHOR.
AB  - OBJECTIVES: The incidence rate of prolonged air leak (PAL) after lobectomy,
      defined as any air leak prolonged beyond 7 days, can be estimated to be in
      between 6 and 15%. In 2011, the Epithor group elaborated an accurate predictive
      score for PAL after open lung resections, so-called IPAL (index of prolonged air
      leak), from a nation-based surgical cohort constituted between 2004 and 2008.
      Since 2008, video-assisted thoracic surgery (VATS) has become popular in France
      among the thoracic surgical community, reaching almost 14% of lobectomies
      performed with this method in 2012. This minimally invasive approach was reported
      as a means to reduce the duration of chest tube drainage. The aim of our study
      was thus to validate the IPAL scoring system in patients having received VATS
      anatomical lung resections. METHODS: We collected all anatomical VATS lung
      resections (lobectomy and segmentectomy) registered in the French national
      general thoracic surgery database (EPITHOR) between 2009 and 2012. The area under
      the receiver operating characteristic (ROC) curve estimated the discriminating
      value of the IPAL score. The slope value described the relation between the
      predicted and observed incidences of PALs. The Hosmer-Lemeshow test was also used
      to estimate the quality of adequacy between predicted and observed values.
      RESULTS: A total of 1233 patients were included: 1037 (84%) lobectomies and 196
      (16%) segmentectomies. In 1099 cases (89.1%), the resection was performed for a
      malignant disease. Ninety-six patients (7.7%) presented with a PAL. The IPAL
      score provided a satisfactory predictive value with an area under the ROC curve
      of 0.72 (0.67-0.77). The value of the slope, 1.25 (0.9-1.58), and the Hosmer
      Lemeshow test (chi(2) = 11, P = 0.35) showed that predicted and observed values
      were adequate. CONCLUSION: The IPAL score is valid for the estimation of the
      predictive risk of PAL after VATS lung resections. It may thus a priori be used
      to characterize any surgical population submitted to potential preventive
      measures.

PMID- 25564215
TI  - Validation of a new approach for mortality risk assessment in oesophagectomy for
      cancer based on age- and gender-corrected body mass index.
AB  - OBJECTIVES: We developed a new algorithm to identify high-risk patients for
      underweight after oesophagectomy for cancer. Patients were assigned to an age
      gender-specific body mass index percentile (AG-BMI) which is then used in a
      survival analysis. This model was able to identify patients more at risk for
      being underweight in comparison with the classically used BMI. It shows a worse
      overall survival (OS) in patients with a preoperative AG-BMI < 10th percentile.
      The aim of this study is to validate this new model based on a cohort of patients
      from an external high-volume institution specialized in oesophageal cancer
      surgery. METHODS: The validation cohort consists of 407 patients operated on
      between 1999 and 2012 with the prerequisite data to calculate AG-BMI and OS. The
      base cohort consisted of 642 consecutive patients, operated on in our institution
      between 2005 and 2010. Age, gender, height and weight on the day before surgery
      were used to calculate the BMI and the AG-BMI. OS was analysed and a multivariate
      analysis was performed. RESULTS: Incidence rates of the AG-BMI < 10th percentile
      risk-patients in the validation cohort showed similar results to our original
      results (17.8 vs 17.2% for the base cohort) with a similar significant OS
      difference between at-risk patients and not-at-risk patients (P < 0.001).
      Multivariate analysis found the same five independent prognosticators for OS in
      both datasets: age, early versus advanced disease, resection status, number of
      positive lymph nodes and the AG-BMI 10th percentile, but not BMI itself. In the
      validation cohort, gender was identified as an additional independent
      prognosticator. The worse OS survival in AG-BMI < 10th percentile in both patient
      populations was related to a significantly higher number of deaths without
      oesophageal cancer recurrence. CONCLUSIONS: This study validates the newly
      developed AG-BMI model to predict more accurately a subgroup of patients at risk
      for worse survival after oesophagectomy. Improved perioperative identification of
      risk factors for poorer OS could help to develop perioperative strategies to
      reduce these risks.

PMID- 25564214
TI  - Negative impact of atrial fibrillation and pulmonary hypertension after mitral
      valve surgery in asymptomatic patients with severe mitral regurgitation: a 20
      year follow-up.
AB  - OBJECTIVES: The timing for mitral valve (MV) surgery in asymptomatic patients
      with severe mitral regurgitation (MR) and preserved left ventricular (LV)
      function remains controversial. We aimed at analysing the long-term outcome of
      asymptomatic patients with atrial fibrillation (AF) and/or pulmonary hypertension
      (PHT) after successful MV repair. METHODS: From January 1992 to December 2012,
      382 patients with severe degenerative MR, with no or mild symptoms, preserved LV
      function (ejection fraction > 60%) and LV systolic dimensions <45 mm were
      submitted to surgery and followed up for up to 22 years (3209 patient-years).
      Patients with associated surgeries, other than tricuspid repair, were excluded.
      Patients with AF and/or PHT (Group A; n = 106, 24.4%) were compared with patients
      without these comorbidities (Group B; n = 276, 63.6%). Propensity-score matching
      (for preoperative variables) was performed obtaining 102 patients in each arm.
      Survival and event-free survival [major cardiac and cerebrovascular events
      (MACCEs); freedom from mitral reoperation and recurrent moderate and severe MR]
      were analysed. RESULTS: MV repair was performed in 98.2% of cases and tricuspid
      annuloplasty in 6.9%. Overall 30-day mortality was 0.8%, not different between
      groups, and absent in patients with isolated posterior leaflet prolapse (n =
      211). Patients with AF/PHT had worse late survival by comparison with Group B
      patients (67.0 +/- 7.4 vs 86.5 +/- 3.9% at 15 years, P < 0.001), survival free
      from MACCE (52.7 +/- 8.7 vs 74.5 +/- 5.0%, P < 0.001), from recurrent moderate
      and severe MR (65.1 +/- 10.3 vs 87.0 +/- 3.8%, P = 0.002) and from mitral
      reoperation during the follow-up (87.3 +/- 6.3 vs 94.2 +/- 2.7%, P = 0.04). These
      differences were confirmed in the propensity score-matched population. Patients
      from Group A also displayed a lesser degree of reverse remodelling. There was a
      significant reduction in the systolic pulmonary artery pressure (SPAP) after
      surgery, more pronounced in Group A patients; nonetheless, the mean SPAP at late
      follow-up was higher in these patients (45 vs 30 mmHg). CONCLUSIONS: MV repair
      can be achieved in the great majority of patients with degenerative
      regurgitation, with low mortality (<1%). Asymptomatic or mildly symptomatic
      patients with severe MR, preserved LV function and AF/PHT had poorer long-term
      survival and event-free survival even after a successful surgery. The durability
      of MV repair was also compromised in these patients, which indicates that they
      should have been operated earlier.

PMID- 25564216
TI  - Extracorporeal life support as a bridge to bridge: a strategy to optimize
      ventricular assist device results.
AB  - OBJECTIVES: Extracorporeal life support (ECLS) devices provide temporary
      mechanical circulatory assistance and are usually implanted under emergency
      conditions in critical patients. If weaning off ECLS is not possible, heart
      transplantation or implantation of long-term mechanical circulatory support
      (LTMCS) is required. The purpose of our study was to evaluate the bridge-to
      bridge (BTB) concept. METHODS: Between 1 January 2004 and 1 August 2010, 97
      patients were assisted by LTMCS. The implantation was the first-line intervention
      in 48 patients (the bridge group), and was performed after a period of ECLS
      support in 49 others (the BTB group). RESULTS: The long-term survival rate was
      51.6%, with a mean follow-up of 30.7 months, and there were no differences for
      biological parameters between the two groups. Patients in the BTB group whose
      condition was initially more severe, improved under ECLS support, and those in
      whom biological parameters did not revert to normal died after LTMCS. Risk
      factors for mortality in the BTB group were total bilirubin and lactate before
      LTMCS, and alkaline phosphatase before ECLS support. CONCLUSIONS: The BTB concept
      allows the implementation of LTMCS in severe patients, for whom it was not
      originally envisaged, with the same long-term survival as in first-line settings.
      ECLS in the evolution of patients is predictive of survival after LTMCS.

PMID- 25564218
TI  - Clinical predictors of early cancer-related mortality following neoadjuvant
      therapy and oesophagectomy.
AB  - OBJECTIVES: Although oesophagectomy can be curative for patients with oesophageal
      cancer (OC), it may be associated with high morbidity and decreased quality of
      life. Identifying risk factors for early systemic progression or death after
      oesophagectomy may help to guide treatment choices in at-risk patients. METHODS:
      Patients undergoing oesophagectomy following neoadjuvant therapy for OC (November
      1987 to January 2013) were reviewed, excluding deaths <=3 months. Univariate
      predictors of death <=1 year of operation were explored by logistic regression.
      Significant predictors (P <= 0.10) were included in a multivariate model. A risk
      factor index was created based on the number of significant risk factors in
      individual patients. RESULTS: Of 581 patients, 238 had neoadjuvant chemotherapy
      or chemotherapy and radiation followed by oesophagectomy. Of these, 15% (n = 36)
      died <=1 year following oesophagectomy and 69% of those from documented cancer
      recurrence. Clinical predictors of death <=1 year by multivariate analysis
      included performance status >0 (HR 2.19; CI 1.02-4.69), poor (G3) tumour
      differentiation (HR 2.67; CI 1.14-6.21) and lack of clinical response (no
      response or progression versus complete and partial response) to neoadjuvant
      therapy (HR 2.77; CI 1.07-7.15). For patients with all factors evaluable (n =
      167), variables were summed to derive a cumulative risk factor index, 0-3. An
      increased risk factor index (>=2) was highly associated with increased risk of
      death <=1 year postoperatively (HR 4.84; CI 1.93-12.16), as well as with poor
      overall survival. CONCLUSIONS: Clinically defined risk factors that predict early
      mortality following oesophagectomy include performance status, poor tumour
      differentiation and clinical response. In patients with at least two of these
      risk factors, 29% will die within 1 year of surgery. These patients should be
      identified and individual consideration given to less morbid surgical strategies
      or to alternative treatments.

PMID- 25564217
TI  - Prognostic model of survival for typical bronchial carcinoid tumours: analysis of
      1109 patients on behalf of the European Association of Thoracic Surgeons (ESTS)
      Neuroendocrine Tumours Working Group.
AB  - OBJECTIVES: Typical carcinoids (TCs) are uncommon, slow-growing neoplasms,
      usually with high 5-year survival rates. As these are rare tumours, their
      management is still based on small clinical observations and no international
      guidelines exist. Based on the European Society of Thoracic Surgeon
      Neuroendocrine Tumours Working Group (NET-WG) Database, we evaluated factors that
      may influence TCs mortality. METHODS: Using the NET-WG database, an analysis on
      TC survival was performed. Overall survival (OS) was calculated starting from the
      date of intervention. Predictors of OS were investigated using the Cox model with
      shared frailty (accounting for the within-centre correlation). Candidate
      predictors were: gender, age, smoking habit, tumour location, previous
      malignancy, Eastern Cooperative Oncology Group (ECOG) performance status (PS),
      pT, pN, TNM stage and tumour vascular invasion. The final model included
      predictors with P <= 0.15 after a backward selection. Missing data in the
      evaluated predictors were multiple-imputed and combined estimates were obtained
      from five imputed data sets. RESULTS: For 58 of 1167 TC patients vital status was
      unavailable and analyses were therefore performed on 1109 patients from 17
      institutions worldwide. During a median follow-up of 50 months, 87 patients died,
      with a 5-year OS rate of 93.7% (95% confidence interval: 91.7-95.3). Backward
      selection resulted in a prediction model for mortality containing age, gender,
      previous malignancies, peripheral tumour, TNM stage and ECOG PS. The final model
      showed a good discrimination ability with a C-statistic equal to 0.836 (bootstrap
      optimism-corrected 0.806). CONCLUSIONS: We presented and validated a promising
      prognostic model for TC survival, showing good calibration and discrimination
      ability. Further analyses are needed and could be focused on an external
      validation of this model.

PMID- 25564219
TI  - Giant left ventricular pseudoaneurysm concomitant with severe mitral
      regurgitation: multimodality imaging and successful surgical repair.

PMID- 25564220
TI  - Highly stable triple helix formation by homopyrimidine (L)-acyclic threoninol
      nucleic acids with single stranded DNA and RNA.
AB  - Acyclic (L)-threoninol nucleic acid (aTNA) containing thymine, cytosine and
      adenine nucleobases were synthesized and shown to form surprisingly stable
      triplexes with complementary single stranded homopurine DNA or RNA targets. The
      triplex structures consist of two (L)-aTNA strands and one DNA or RNA, and these
      triplexes are significantly stronger than the corresponding DNA or RNA duplexes
      as shown in competition experiments. As a unique property the (L)-aTNAs
      exclusively form triplex structures with DNA and RNA and no duplex structures are
      observed by gel electrophoresis. The results were compared to the known
      enantiomer (D)-aTNA, which forms much weaker triplexes depending upon temperature
      and time. It was demonstrated that (L)-aTNA triplexes are able to stop primer
      extension on a DNA template, showing the potential of (L)-aTNA for antisense
      applications.

PMID- 25564221
TI  - A systematic review of patient-reported outcome instruments of dermatologic
      adverse events associated with targeted cancer therapies.
AB  - PURPOSE: Dermatologic adverse events (dAEs) in cancer treatment are frequent with
      the use of targeted therapies. These dAEs have been shown to have significant
      impact on health-related quality of life (HRQoL). While standardized assessment
      tools have been developed for physicians to assess severity of dAEs, there is a
      discord between objective and subjective measures. The identification of patient
      reported outcome (PRO) instruments useful in the context of targeted cancer
      therapies is therefore important in both the clinical and research settings for
      the overall evaluation of dAEs and their impact on HRQoL. METHODS: A
      comprehensive, systematic literature search of published articles was conducted
      by two independent reviewers in order to identify PRO instruments previously
      utilized in patient populations with dAEs from targeted cancer therapies. The
      identified PRO instruments were studied to determine which HRQoL issues relevant
      to dAEs were addressed, as well as the process of development and validation of
      these instruments. RESULTS: Thirteen articles identifying six PRO instruments met
      the inclusion criteria. Four instruments were general dermatology (Skindex-16(c),
      Skindex-29(c), Dermatology Life Quality Index (DLQI), and DIELH-24) and two were
      symptom-specific (functional assessment of cancer therapy-epidermal growth factor
      receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome 14 (HFS-14)).
      CONCLUSIONS: While there are several PRO instruments that have been tested in the
      context of targeted cancer therapy, additional work is needed to develop new
      instruments and to further validate the instruments identified in this study in
      patients receiving targeted therapies.

PMID- 25564223
TI  - Opioids have no negative effect on the survival time of patients with advanced
      lung cancer in an acute care hospital.
AB  - PURPOSE: The purpose of this study is to determine whether or not opioid
      administration influenced the survival time of patients with advanced lung cancer
      in an acute care hospital setting. METHODS: This was a single institutional and
      retrospective study. We reviewed patients with advanced lung cancer who had died
      from January 2008 to December 2013 at the Osaka Police Hospital. We compared
      survival times, calculated from the time of the last hospitalization or the last
      chemotherapy, between patients who had not used any opioids, those who had used a
      low dose of opioids (< 60 mg/day), and those who had used a higher dose of
      opioids (>= 60 mg/day). RESULTS: A total of 369 patients, of which 284 had
      received chemotherapy, were analyzed. Opioid users were generally younger than
      nonusers. There was no significant difference in survival time after the last
      hospitalization in terms of opioid dose at the last admission and mean daily
      opioid dose; there was also no significant difference in survival time after the
      last chemotherapy in terms of the mean daily opioid dose and the opioid dose at
      death. Univariate and multivariate Cox proportional hazard analysis regarding
      survival time after the last hospitalization or the last chemotherapy did not
      reveal any opioid-related variables as a significant predictive factor.
      CONCLUSIONS: Opioids were found to have no negative influence on survival time
      even in an acute care hospital.

PMID- 25564222
TI  - Value of lipopolysaccharide binding protein as diagnostic marker of infection in
      adult cancer patients with febrile neutropenia: comparison with C-reactive
      protein, procalcitonin, and interleukin 6.
AB  - PURPOSE: Early detection of infection is essential for initial management of
      cancer patients with chemotherapy-associated febrile neutropenia in the emergency
      department. In this study, we evaluated lipopolysaccharide binding protein (LBP)
      as predictor for infection in febrile neutropenia and compared with other
      biomarkers previously studied: C-reactive protein (CRP), procalcitonin (PCT), and
      interleukin (IL)-6. METHODS: A total of 61 episodes of chemotherapy-associated
      febrile neutropenia in 58 adult cancer patients were included. Serum samples were
      collected on admission at emergency department and CRP, LBP, PCT, and IL-6 were
      measured. Patients were classified into fever of unknown origin and infection,
      including microbiologically and clinically documented infection, groups. Receiver
      operating characteristic (ROC) curve analysis was performed for each biomarker
      for the diagnosis of infection. RESULTS: Thirty-two of the 61 episodes were
      classified as infection. On admission, CRP, PCT, IL-6, and LBP were significantly
      increased in patients with infection compared to fever of unknown origin group.
      Area under the ROC curve (AUC ROC) of CRP, PCT, IL-6, and LBP for discriminating
      both groups was 0.77, 0.88, 0.82, and 0.82, respectively, without significant
      difference between them. The combination of IL-6 and PCT or LBP did not lead to a
      significant improvement of the diagnostic accuracy of PCT or LBP alone.
      CONCLUSIONS: On admission, LBP has a similar diagnostic accuracy than PCT or IL-6
      for the diagnosis of infection and might be used as additional diagnostic tool in
      adult cancer patients with chemotherapy-associated febrile neutropenia.

PMID- 25564225
TI  - A colorimetric nitrite detection system with excellent selectivity and high
      sensitivity based on Ag@Au nanoparticles.
AB  - Excessive uptake of NO2(-) is detrimental to human health, but the currently
      available methods used to sensitively detect this ion in the environment are
      cumbersome and expensive. In this study, we developed an improved NO2(-)
      detection system based on a redox etching strategy of CTAB-stabilized Ag-Au core
      shell nanoparticles (Ag@AuNPs). The detection mechanism was verified by UV-Vis
      spectroscopy, TEM and XPS. The detection system produces a color change from
      purple to colorless in response to an increase of NO2(-) concentration. The
      selectivity of detection of NO2(-), both with the unaided eye and by measurement
      of UV-Vis spectra, is excellent in relation to other ions, including Cu(2+),
      Co(2+), Ni(2+), Cr(3+), Al(3+), Pb(2+), Cd(2+), Ca(2+), Ba(2+), Zn(2+), Mn(2+),
      Mg(2+), Fe(3+), Hg(2+), Ag(+), K(+), F(-), PO4(3-), C2O4(2-), SO3(2-), CO3(2-),
      SO4(2-), NO3(-) and CH3-COO(-) (Ac(-)). The limit of detection (LOD) for NO2(-)
      is 1.0 MUM by eye and 0.1 MUM by UV-Vis spectroscopy. The LOD by eye is lower
      than the lowest previously reported value (4.0 MUM). There is a good linear
      relationship between A/A0 and the concentration of NO2(-) from 1.0 to 20.0 MUM
      NO2(-), which permits a quantitative assay. The applicability of our detection
      system was also verified by analysis of NO2(-) in tap water and lake water. The
      results demonstrate that our Ag@AuNP-based detection system can be used for the
      rapid colorimetric detection of NO2(-) in complex environmental samples, with
      excellent selectivity and high sensitivity. 

PMID- 25564224
TI  - STAT2/IRF9 directs a prolonged ISGF3-like transcriptional response and antiviral
      activity in the absence of STAT1.
AB  - Evidence is accumulating for the existence of a signal transducer and activator
      of transcription 2 (STAT2)/interferon regulatory factor 9 (IRF9)-dependent, STAT1
      independent interferon alpha (IFNalpha) signalling pathway. However, no detailed
      insight exists into the genome-wide transcriptional regulation and the biological
      implications of STAT2/IRF9-dependent IFNalpha signalling as compared with
      interferon-stimulated gene factor 3 (ISGF3). In STAT1-defeicient U3C cells stably
      overexpressing human STAT2 (hST2-U3C) and STAT1-deficient murine embryonic
      fibroblast cells stably overexpressing mouse STAT2 (mST2-MS1KO) we observed that
      the IFNalpha-induced expression of 2'-5'-oligoadenylate synthase 2 (OAS2) and
      interferon-induced protein with tetratricopeptide repeats 1 (Ifit1) correlated
      with the kinetics of STAT2 phosphorylation, and the presence of a STAT2/IRF9
      complex requiring STAT2 phosphorylation and the STAT2 transactivation domain.
      Subsequent microarray analysis of IFNalpha-treated wild-type (WT) and STAT1 KO
      cells overexpressing STAT2 extended our observations and identified ~120 known
      antiviral ISRE-containing interferon-stimulated genes (ISGs) commonly up
      regulated by STAT2/IRF9 and ISGF3. The STAT2/IRF9-directed expression profile of
      these IFN-stimulated genes (ISGs) was prolonged as compared with the early and
      transient response mediated by ISGF3. In addition, we identified a group of
      'STAT2/IRF9-specific' ISGs, whose response to IFNalpha was ISGF3-independent.
      Finally, STAT2/IRF9 was able to trigger an antiviral response upon
      encephalomyocarditis virus (EMCV) and vesicular stomatitis Indiana virus (VSV).
      Our results further prove that IFNalpha-activated STAT2/IRF9 induces a prolonged
      ISGF3-like transcriptome and generates an antiviral response in the absence of
      STAT1. Moreover, the existence of 'STAT2/IRF9-specific' target genes predicts a
      novel role of STAT2 in IFNalpha signalling. 

PMID- 25564226
TI  - A novel treatment for bone lesions of multifocal epithelioid sarcoma-like
      hemangioendothelioma.
AB  - Epithelioid sarcoma-like hemangioendothelioma (ES-H) is a rare, indolent vascular
      neoplasm with characteristics similar to epithelioid sarcoma. It typically
      affects young males who present with skin and subcutaneous lesions in the
      extremities. Bone lesions, occurring in approximately 20% of patients, are often
      multifocal, seen in conjunction with soft tissue lesions, and usually found in
      bones of the lower extremities. This report details the case of a 20-year-old
      male who presented with a 1-year history of painful skin lesions on his left
      lower extremity. Staging studies revealed bone lesions in the cuboid and
      calcaneus. Bone and soft tissue pathology was consistent with ES-H. The soft
      tissue lesions were treated with wide excision and the bony lesions with
      radiofrequency ablation (RFA). The patient had no evidence of recurrence at the 2
      year follow-up. Treatment of ES-H typically consists of wide excision of all soft
      tissue lesions and possible adjuvant radiation therapy. Management of bony
      lesions has included marginal excision, wide excision, amputation, chemotherapy,
      observation, or a combination of these modalities. ES-H has the potential for
      distant metastases. There is no consensus regarding the appropriate treatment of
      multifocal epithelioid sarcoma-like hemangioendothelioma involving bone. A
      potential treatment strategy of wide excision of soft tissue lesions and RFA of
      bone lesions is proposed.

PMID- 25564227
TI  - Case series: the application of "third wave" cognitive behavioural therapies in
      difficult to treat asthma.
AB  - OBJECTIVE: This paper provides for the first time cases of individual
      psychological therapy undertaken in tertiary, difficult to treat asthma services
      using "third wave" cognitive behavioural therapy (CBT) approaches. METHODS: These
      cases were selected to represent common psychological presentations in difficult
      to treat asthma clinics, namely denial of severity and over-identification with
      asthma. Assessment, formulation, intervention and results are outlined. RESULTS:
      Case 1 demonstrated change from severe to mild depression and anxiety, reduction
      in shame and improved well-being. Case 2 demonstrated improvements in well-being
      and psychological symptoms. Both interventions were experienced by the patients
      as highly satisfactory. CONCLUSIONS: It is concluded that a psychological
      understanding of patients' presentations can open up new avenues for
      intervention. Further research into the potential utility of third wave cognitive
      therapies in difficult to treat asthma is warranted.

PMID- 25564228
TI  - Population frequencies of the Triallelic 5HTTLPR in six Ethnicially diverse
      samples from North America, Southeast Asia, and Africa.
AB  - Genetic differences between populations are potentially an important contributor
      to health disparities around the globe. As differences in gene frequencies
      influence study design, it is important to have a thorough understanding of the
      natural variation of the genetic variant(s) of interest. Along these lines, we
      characterized the variation of the 5HTTLPR and rs25531 polymorphisms in six
      samples from North America, Southeast Asia, and Africa (Cameroon) that differ in
      their racial and ethnic composition. Allele and genotype frequencies were
      determined for 24,066 participants. Results indicated higher frequencies of the
      rs25531 G-allele among Black and African populations as compared with White,
      Hispanic and Asian populations. Further, we observed a greater number of 'extra
      long' ('XL') 5HTTLPR alleles than have previously been reported. Extra-long
      alleles occurred almost entirely among Asian, Black and Non-White Hispanic
      populations as compared with White and Native American populations where they
      were completely absent. Lastly, when considered jointly, we observed between
      sample differences in the genotype frequencies within racial and ethnic
      populations. Taken together, these data underscore the importance of
      characterizing the L-G allele to avoid misclassification of participants by
      genotype and for further studies of the impact XL alleles may have on the
      transcriptional efficiency of SLC6A4. 

PMID- 25564229
TI  - Postsynaptic and spiking activity of pyramidal cells, the principal neurons in
      the rat hippocampal CA1 region, does not control the resultant BOLD response: a
      combined electrophysiologic and fMRI approach.
AB  - The specific role of postsynaptic activity for the generation of a functional
      magnetic resonance imaging (fMRI) response was determined by a simultaneous
      measurement of generated field excitatory postsynaptic potentials (fEPSPs) and
      blood oxygen level-dependent (BOLD) response in the rat hippocampal CA1 region
      during electrical stimulation of the contralateral CA3 region. The stimulation
      electrode was placed either in the left CA3a/b or CA3c, causing the
      preferentially basal or apical dendrites of the pyramidal cells in the right CA1
      to be activated. Consecutive stimulations with low-intensity stimulation trains
      (i.e., 16 pulses for 8 seconds) resulted in clear postsynaptic responses of CA1
      pyramidal cells, but in no significant BOLD responses. In contrast, consecutive
      high-intensity stimulation trains resulted in stronger postsynaptic responses
      that came along with minor (during stimulation of the left CA3a/b) or substantial
      (during stimulation of the left CA3c) spiking activity of the CA1 pyramidal
      cells, and resulted in the generation of significant BOLD responses in the left
      and right hippocampus. Correlating the electrophysiologic parameters of CA1
      pyramidal cell activity (fEPSP and spiking activity) with the resultant BOLD
      response revealed no positive correlation. Consequently, postsynaptic activity of
      pyramidal cells, the most abundant neurons in the CA1, is not directly linked to
      the measured BOLD response.

PMID- 25564231
TI  - Unexpected complication in a rat stroke model: exacerbation of secondary
      pathology in the thalamus by subacute intraarterial administration of human bone
      marrow-derived mesenchymal stem cells.
AB  - This study examined whether human bone marrow mesenchymal stromal/stem cells
      (BMMSCs) could alleviate the secondary pathology in the thalamus after middle
      cerebral artery occlusion (MCAO) in rats. Atypical accumulation of both amyloid
      beta (Abeta) and calcium in the thalamus was significantly higher in rats
      receiving the BMMSCs infusion 48 hours after MCAO as compared with the vehicle
      MCAO group. The elevated Abeta/calcium accumulation correlated with the level of
      impaired sensorimotor function. Although secondary pathology in the thalamus
      seems to be rodent specific, it needs to be taken into account because it may
      impair long-term behavioral recovery and negate therapeutic treatment effects. 

PMID- 25564230
TI  - Simvastatin restored vascular reactivity, endothelial function and reduced string
      vessel pathology in a mouse model of cerebrovascular disease.
AB  - Cerebrovascular dysfunction seen in Alzheimer's disease (AD) and vascular
      dementia (VaD) is multifaceted and not limited to the amyloid-beta (Abeta)
      pathology. It encompasses structural alterations in the vessel wall, degenerating
      capillaries (string vessels), vascular fibrosis and calcification, features
      recapitulated in transgenic mice that overexpress transforming growth factor
      beta1 (TGF mice). We recently found that simvastatin rescued Abeta-mediated
      cerebrovascular and cognitive deficits in a transgenic mouse model of AD.
      However, whether simvastatin can counteract Abeta-independent deficits remains
      unknown. Here, we evaluated the effects of simvastatin in aged TGF mice on
      cerebrovascular reactivity and structure, and on cognitive performance.
      Simvastatin restored baseline levels of nitric oxide (NO), NO-, and KATP channel
      mediated dilations and endothelin-1-induced contractions. Simvastatin
      significantly reduced vasculopathy with arteriogenic remodeling and string vessel
      pathology in TGF mice. In contrast, simvastatin did not lessen gliosis, and the
      cerebrovascular levels of pro-fibrotic proteins and calcification markers
      remained elevated after treatment. The TGF mice displayed subtle cognitive
      decline that was not affected by simvastatin. Our results show potent benefits of
      simvastatin on endothelial- and smooth muscle cell-mediated vasomotor responses,
      endothelial NO synthesis and in preserving capillary integrity. We conclude that
      simvastatin could be indicated in the treatment of cerebrovascular dysfunction
      associated with VaD and AD. 

PMID- 25564232
TI  - The relationship between glucose metabolism, resting-state fMRI BOLD signal, and
      GABAA-binding potential: a preliminary study in healthy subjects and those with
      temporal lobe epilepsy.
AB  - Glucose metabolism has been associated with magnitude of blood oxygen level
      dependent (BOLD) signal and connectivity across subjects within the default mode
      and dorsal attention networks. Similar correlations within subjects across the
      entire brain remain unexplored. [(18)F]-fluorodeoxyglucose positron emission
      tomography ([(18)F]-FDG PET), [(11)C]-flumazenil PET, and resting-state
      functional magnetic resonance imaging (fMRI) scans were acquired in eight healthy
      individuals and nine with temporal lobe epilepsy (TLE). Regional metabolic rate
      of glucose (rMRGlu) was correlated with amplitude of low frequency fluctuations
      (ALFFs) in the fMRI signal, global fMRI connectivity (GC), regional homogeneity
      (ReHo), and gamma-aminobutyric acid A-binding potential (GABAA BP(ND)) across the
      brain. Partial correlations for ALFFs, GC, and ReHo with GABAA BP(ND) were
      calculated, controlling for rMRGlu. In healthy subjects, significant positive
      correlations were observed across the brain between rMRGlu and ALFF, ReHo and
      GABAA BP(ND), and between ALFFs and GABAA BP(ND), controlling for rMRGlu. Brain
      wide correlations between rMRGlu and ALFFs were significantly lower in TLE
      patients, and correlations between rMRGlu and GC were significantly greater in
      TLE than healthy subjects. These results indicate that the glutamatergic and
      GABAergic systems are coupled across the healthy human brain, and that ALFF is
      related to glutamate use throughout the healthy human brain. TLE may be a
      disorder of altered long-range connectivity in association with glutamate
      function.

PMID- 25564233
TI  - Postischemic hyperperfusion on arterial spin labeled perfusion MRI is linked to
      hemorrhagic transformation in stroke.
AB  - The purpose of this study was to investigate the relationship between
      hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke
      (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed
      3D GRASE was performed during routine clinical magnetic resonance imaging (MRI)
      on AIS patients at various time points. Arterial spin labeling cerebral blood
      flow (CBF) maps were visually inspected for the presence of hyperperfusion.
      Hemorrhagic transformation was followed during hospitalization and was graded on
      gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and
      parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221
      consecutive patients with middle cerebral artery stroke from May 2010 to
      September 2013. Hyperperfusion was more frequently detected posttreatment (odds
      ratio (OR) = 4.8, 95% confidence interval (CI) 2.5 to 8.9, P < 0.001) and with
      high National Institutes of Health Stroke Scale (NIHSS) scores at admission
      (P<0.001). There was a significant association between having hyperperfusion at
      any time point and HT (OR = 3.5, 95% CI 2.0 to 6.3, P < 0.001). There was a
      positive relationship between the grade of HT and time-hyperperfusion with the
      Spearman's rank correlation of 0.44 (P = 0.003). Arterial spin labeling
      hyperperfusion may provide an imaging marker of HT, which may guide the
      management of AIS patients post tissue-type plasminogen activator (tPA) and/or
      endovascular treatments. Late hyperperfusion should be given more attention to
      prevent high-grade HT.

PMID- 25564234
TI  - Blood flow distribution in cerebral arteries.
AB  - High-resolution phase-contrast magnetic resonance imaging can now assess flow in
      proximal and distal cerebral arteries. The aim of this study was to describe how
      total cerebral blood flow (tCBF) is distributed into the vascular tree with
      regard to age, sex and anatomic variations. Forty-nine healthy young (mean 25
      years) and 45 elderly (mean 71 years) individuals were included. Blood flow rate
      (BFR) in 21 intra- and extracerebral arteries was measured. Total cerebral blood
      flow was defined as BFR in the internal carotid plus vertebral arteries and mean
      cerebral perfusion as tCBF/brain volume. Carotid/vertebral distribution was
      72%/28% and was not related to age, sex, or brain volume. Total cerebral blood
      flow (717 +/- 123 mL/min) was distributed to each side as follows: middle
      cerebral artery (MCA), 21%; distal MCA, 6%; anterior cerebral artery (ACA), 12%,
      distal ACA, 4%; ophthalmic artery, 2%; posterior cerebral artery (PCA), 8%; and
      20% to basilar artery. Deviating distributions were observed in subjects with
      'fetal' PCA. Blood flow rate in cerebral arteries decreased with increasing age
      (P<0.05) but not in extracerebral arteries. Mean cerebral perfusion was higher in
      women (women: 61 +/- 8; men: 55 +/- 6 mL/min/100 mL, P<0.001). The study
      describes a new method to outline the flow profile of the cerebral vascular tree,
      including reference values, and should be used for grading the collateral flow
      system.

PMID- 25564235
TI  - Mast cells promote blood brain barrier breakdown and neutrophil infiltration in a
      mouse model of focal cerebral ischemia.
AB  - Blood brain barrier (BBB) breakdown and neuroinflammation are key events in
      ischemic stroke morbidity and mortality. The present study investigated the
      effects of mast cell deficiency and stabilization on BBB breakdown and neutrophil
      infiltration in mice after transient middle cerebral artery occlusion (tMCAo).
      Adult male C57BL6/J wild type (WT) and mast cell-deficient (C57BL6/J Kit(Wsh/Wsh)
      (Wsh)) mice underwent tMCAo and BBB breakdown, brain edema and neutrophil
      infiltration were examined after 4 hours of reperfusion. Blood brain barrier
      breakdown, brain edema, and neutrophil infiltration were significantly reduced in
      Wsh versus WT mice (P<0.05). These results were reproduced pharmacologically
      using mast cell stabilizer, cromoglycate. Wild-type mice administered
      cromoglycate intraventricularly exhibited reduced BBB breakdown, brain edema, and
      neutrophil infiltration versus vehicle (P<0.05). There was no effect of
      cromoglycate versus vehicle in Wsh mice, validating specificity of cromoglycate
      on brain mast cells. Proteomic analysis in Wsh versus WT indicated that effects
      may be via expression of endoglin, endothelin-1, and matrix metalloproteinase-9.
      Using an in vivo model of mast cell deficiency, this is the first study showing
      that mast cells promote BBB breakdown in focal ischemia in mice, and opens up
      future opportunities for using mice to identify specific mechanisms of mast cell
      related BBB injury.

PMID- 25564237
TI  - Characterization of blood flow in the mouse dorsal spinal venous system before
      and after dorsal spinal vein occlusion.
AB  - The availability of transgenic strains has made the laboratory mouse a popular
      model for the study of healthy and diseased state spinal cord (SC). Essential to
      identifying physiologic and pathologic events is an understanding of the
      microvascular network and flow patterns of the SC. Using 2-photon excited
      fluorescence (2PEF) microscopy we performed in vivo measurements of blood flow in
      the lower thoracic portion of the mouse dorsal spinal vein (dSV) and in the first
      upstream branches supplying it, denoted as dorsal ascending venules (dAVs). We
      found that the dSV had large radiculomedullary veins (RMVs) exiting the SC, and
      that flow in the dSV between pairs of RMVs was bidirectional. Volumetric flow
      increased in each direction away from the point of bifurcation. Flow in the
      upstream dAVs varied with diameter in a manner consistent with a constant distal
      pressure source. By performing ex vivo 2PEF microscopy of fluorescent-gel
      perfused tissue, we created a 3-D map of the dorsal spinal vasculature. From
      these data, we constructed a simple model that predicted changes in the flow of
      upstream branches after occlusion of the dSV in different locations. Using an
      atraumatic model of dSV occlusion, we confirmed the predictions of this model in
      vivo. 

PMID- 25564236
TI  - Neurochemical and BOLD responses during neuronal activation measured in the human
      visual cortex at 7 Tesla.
AB  - Several laboratories have consistently reported small concentration changes in
      lactate, glutamate, aspartate, and glucose in the human cortex during prolonged
      stimuli. However, whether such changes correlate with blood oxygenation level
      dependent functional magnetic resonance imaging (BOLD-fMRI) signals have not been
      determined. The present study aimed at characterizing the relationship between
      metabolite concentrations and BOLD-fMRI signals during a block-designed paradigm
      of visual stimulation. Functional magnetic resonance spectroscopy (fMRS) and fMRI
      data were acquired from 12 volunteers. A short echo-time semi-LASER localization
      sequence optimized for 7 Tesla was used to achieve full signal-intensity MRS
      data. The group analysis confirmed that during stimulation lactate and glutamate
      increased by 0.26 +/- 0.06 MUmol/g (~30%) and 0.28 +/- 0.03 MUmol/g (~3%),
      respectively, while aspartate and glucose decreased by 0.20 +/- 0.04 MUmol/g
      (~5%) and 0.19 +/- 0.03 MUmol/g (~16%), respectively. The single-subject analysis
      revealed that BOLD-fMRI signals were positively correlated with glutamate and
      lactate concentration changes. The results show a linear relationship between
      metabolic and BOLD responses in the presence of strong excitatory sensory inputs,
      and support the notion that increased functional energy demands are sustained by
      oxidative metabolism. In addition, BOLD signals were inversely correlated with
      baseline gamma-aminobutyric acid concentration. Finally, we discussed the
      critical importance of taking into account linewidth effects on metabolite
      quantification in fMRS paradigms.

PMID- 25564238
TI  - Effects of a high-caloric diet and physical exercise on brain metabolite levels:
      a combined proton MRS and histologic study.
AB  - Excessive intake of high-caloric diets as well as subsequent development of
      obesity and diabetes mellitus may exert a wide range of unfavorable effects on
      the central nervous system (CNS). It has been suggested that one mechanism in
      this context is the promotion of neuroinflammation. The potentially harmful
      effects of such diets were suggested to be mitigated by physical exercise. Here,
      we conducted a study investigating the effects of physical exercise in a
      cafeteria-diet mouse model on CNS metabolites by means of in vivo proton magnetic
      resonance spectroscopy ((1)HMRS). In addition postmortem histologic and real-time
      (RT)-PCR analyses for inflammatory markers were performed. Cafeteria diet induced
      obesity and hyperglycemia, which was only partially moderated by exercise. It
      also induced several changes in CNS metabolites such as reduced hippocampal
      glutamate (Glu), choline-containing compounds (tCho) and N-acetylaspartate
      (NAA)+N-acetyl-aspartyl-glutamic acid (NAAG) (tNAA) levels, whereas opposite
      effects were seen for running. No association of these effects with markers of
      central inflammation could be observed. These findings suggest that while
      voluntary wheel running alone is insufficient to prevent the unfavorable
      peripheral sequelae of the diet, it counteracted many changes in brain
      metabolites. The observed effects seem to be independent of neuroinflammation. 

PMID- 25564239
TI  - Reference region modeling approaches for amphetamine challenge studies with
      [11C]FLB 457 and PET.
AB  - Detecting fluctuations in synaptic dopamine levels in extrastriatal brain regions
      with [(11)C]FLB 457 and positron emission tomography (PET) is a valuable tool for
      studying dopaminergic dysfunction in psychiatric disorders. The evaluation of
      reference region modeling approaches would eliminate the need to obtain arterial
      input function data. Our goal was to explore the use of reference region models
      to estimate amphetamine-induced changes in [(11)C]FLB 457 dopamine D2/D3 binding.
      Six healthy tobacco smokers were imaged with [(11)C]FLB 457 at baseline and at 3
      hours after amphetamine (0.4 to 0.5 mg/kg, per os) administration. Simplified
      reference tissue models, SRTM and SRTM2, were evaluated against the 2-tissue
      compartmental model (2TC) to estimate [(11)C]FLB 457 binding in extrastriatal
      regions of interest (ROIs), using the cerebellum as a reference region. No
      changes in distribution volume were observed in the cerebellum between scan
      conditions. SRTM and SRTM2 underestimated binding, compared with 2TC, in ROIs by
      26% and 9%, respectively, with consistent bias between the baseline and
      postamphetamine scans. Postamphetamine, [(11)C]FLB 457 binding significantly
      decreased across several brain regions as measured with SRTM and SRTM2; no
      significant change was detected with 2TC. These data support the sensitivity of
      [(11)C]FLB 457 for measuring amphetamine-induced dopamine release in
      extrastriatal regions with SRTM and SRTM2.

PMID- 25564242
TI  - In memoriam: William Feindel, O.C., G.O.Q., MDCM, D. Phil; July 12, 1918-January
      12, 2014.

PMID- 25564240
TI  - Rewarming from therapeutic hypothermia induces cortical neuron apoptosis in a
      swine model of neonatal hypoxic-ischemic encephalopathy.
AB  - The consequences of therapeutic hypothermia for neonatal hypoxic-ischemic
      encephalopathy are poorly understood. Adverse effects from suboptimal rewarming
      could diminish neuroprotection from hypothermia. Therefore, we tested whether
      rewarming is associated with apoptosis. Piglets underwent hypoxia-asphyxia
      followed by normothermic or hypothermic recovery at 2 hours. Hypothermic groups
      were divided into those with no rewarming, rewarming at 0.5  degrees C/hour, or
      rewarming at 4  degrees C/hour. Neurodegeneration at 29 hours was assessed by
      hematoxylin and eosin staining, TUNEL assay, and immunoblotting for cleaved
      caspase-3. Rewarmed piglets had more apoptosis in motor cortex than did those
      that remained hypothermic after hypoxia-asphyxia. Apoptosis in piriform cortex
      was greater in hypoxic-asphyxic, rewarmed piglets than in naive/sham piglets.
      Caspase-3 inhibitor suppressed apoptosis with rewarming. Rapidly rewarmed piglets
      had more caspase-3 cleavage in cerebral cortex than did piglets that remained
      hypothermic or piglets that were rewarmed slowly. We conclude that rewarming from
      therapeutic hypothermia can adversely affect the newborn brain by inducing
      apoptosis through caspase mechanisms.

PMID- 25564241
TI  - Quantification of [(11)C]yohimbine binding to alpha2 adrenoceptors in rat brain
      in vivo.
AB  - We quantified the binding potentials (BPND) of [(11)C]yohimbine binding in rat
      brain to alpha-2 adrenoceptors to evaluate [(11)C]yohimbine as an in vivo marker
      of noradrenergic neurotransmission and to examine its sensitivity to the level of
      noradrenaline. Dual [(11)C]yohimbine dynamic positron emission tomography (PET)
      recordings were applied to five Sprague Dawley rats at baseline, followed by
      acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous
      level of noradrenaline. The volume of distribution (VT) of [(11)C]yohimbine was
      obtained using Logan plot with arterial plasma input. Because alpha-2
      adrenoceptors are distributed throughout the brain, the estimation of the BPND is
      complicated by the absence of an anatomic region of no displaceable binding. We
      used the Inhibition plot to acquire the reference volume, VND, from which we
      calculated the BPND. Acute pharmacological challenge with amphetamine induced a
      significant decline of [(11)C]yohimbine BPND of ~38% in all volumes of interest.
      The BPND was greatest in the thalamus and striatum, followed in descending order
      by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that
      [(11)C]yohimbine binding is sensitive to a challenge known to increase the
      extracellular level of noradrenaline, which can benefit future PET investigations
      of pathologic conditions related to disrupted noradrenergic neurotransmission. 

PMID- 25564244
TI  - Bioinspired nanovalves with selective permeability and pH sensitivity.
AB  - Biological systems with controlled permeability and release functionality, which
      are among the successful examples of living beings to survive in evolution, have
      attracted intensive investigation and have been mimicked due to their broad
      spectrum of applications. We present in this work, for the first time, an example
      of nuclear pore complexes (NPCs)-inspired controlled release system that exhibits
      on-demand release of angstrom-sized molecules. We do so in a cost-effective way
      by stabilizing porous cobalt basic carbonates as nanovalves and realizing pH
      sensitive release of entrapped subnano cargo. The proof-of-concept work also
      consists of the establishment of two mathematical models to explain the selective
      permeability of the nanovalves. Finally, gram-sized (or larger) quantities of the
      bio-inspired controlled release system can be synthesized through a scaling-up
      strategy, which opens up opportunities for controlled release of functional
      molecules in wider practical applications. 

PMID- 25564243
TI  - Rapid assessment of nonlinear optical propagation effects in dielectrics.
AB  - Ultrafast laser processing applications need fast approaches to assess the
      nonlinear propagation of the laser beam in order to predict the optimal range of
      processing parameters in a wide variety of cases. We develop here a method based
      on the simple monitoring of the nonlinear beam shaping against numerical
      prediction. The numerical code solves the nonlinear Schrodinger equation with
      nonlinear absorption under simplified conditions by employing a state-of-the art
      computationally efficient approach. By comparing with experimental results we can
      rapidly estimate the nonlinear refractive index and nonlinear absorption
      coefficients of the material. The validity of this approach has been tested in a
      variety of experiments where nonlinearities play a key role, like spatial soliton
      shaping or fs-laser waveguide writing. The approach provides excellent results
      for propagated power densities for which free carrier generation effects can be
      neglected. Above such a threshold, the peculiarities of the nonlinear propagation
      of elliptical beams enable acquiring an instantaneous picture of the deposition
      of energy inside the material realistic enough to estimate the effective
      nonlinear refractive index and nonlinear absorption coefficients that can be used
      for predicting the spatial distribution of energy deposition inside the material
      and controlling the beam in the writing process. 

PMID- 25564245
TI  - Hollow carbon nanospheres/silicon/alumina core-shell film as an anode for lithium
      ion batteries.
AB  - Hollow carbon nanospheres/silicon/alumina (CNS/Si/Al2O3) core-shell films
      obtained by the deposition of Si and Al2O3 on hollow CNS interconnected films are
      used as the anode materials for lithium-ion batteries. The hollow CNS film acts
      as a three dimensional conductive substrate and provides void space for silicon
      volume expansion during electrochemical cycling. The Al2O3 thin layer is
      beneficial to the reduction of solid-electrolyte interphase (SEI) formation.
      Moreover, as-designed structure holds the robust surface-to-surface contact
      between Si and CNSs, which facilitates the fast electron transport. As a
      consequence, the electrode exhibits high specific capacity and remarkable
      capacity retention simultaneously: 1560 mA h g(-1) after 100 cycles at a current
      density of 1 A g(-1) with the capacity retention of 85% and an average decay rate
      of 0.16% per cycle. The superior battery properties are further confirmed by
      cyclic voltammetry (CV) and impedance measurement.

PMID- 25564246
TI  - Selective, direct detection of acetylcholine in PBS solution, with self-assembled
      fluorescent nano-particles: experiment and modelling.
AB  - We report synthesis, characterisation and molecular modelling of a new
      fluorescent cyclotriveratrylene probe for acetylcholine in aqueous media, with
      emission around 430 nm thanks to extended conjugation. The probe discriminates
      acetylcholine from choline, with respective binding constants 540 and 240 M(-1)
      in PBS buffered saline solution, an order of magnitude improvement over the
      previous best performance. Dynamic light scattering and transmission electron
      microscopy show the new probe self-assembles in ca. 5 nm diameter particles in
      PBS medium. Molecular modelling suggests that the high fluorescence quantum yield
      of the probe, 20% in aqueous media, is due to features of the molecular
      arrangement in the nano-particles, contributing both to exposure of the
      complexation site and to shielding of the fluorescent pi system from quenching by
      water. Titration data for other quaternary ammoniums and modelling indicate that
      recognition of acetylcholine vs. choline depends on specific electrostatic
      interactions, and to a lesser extent on exclusion of water by hydrophobic
      hydrophilic segregation. Probe-substrate interactions enhance the fluorescence of
      the probe by shielding against water and by flattening the pi system. 

PMID- 25564247
TI  - Rh(III)-catalyzed C-H activation/cyclization of benzamides and diazo compounds to
      form isocoumarins and alpha-pyrones.
AB  - Rhodium-catalyzed intermolecular cyclization of benzamides and diazo compounds
      via C-H activation has been achieved to construct C-C/C-O bonds for the first
      time. The process provides a facile approach for the construction of isocoumarins
      and alpha-pyrones without the need for high temperature or adding oxidants. 

PMID- 25564248
TI  - Benzotriazole and 5-methylbenzotriazole in recycled water, surface water and
      dishwashing detergents from Perth, Western Australia: analytical method
      development and application.
AB  - A simplified and sensitive liquid chromatography mass spectrometry (LC-MS) method
      without requiring sample pre-concentration was successfully developed for
      detecting the occurrence of ultra-low (ng L(-1)) concentrations of benzotriazole
      (BTri), and its derivative 5-methyl benzotriazole (5-MeBT) in various Western
      Australian environmental water samples. The method detection limit was 2 ng L(
      1), providing similar detection limits to other more process intensive methods
      where pre-concentration using solid phase extraction (SPE) was employed. The
      method was used to assess the occurrence of BTri and 5-MeBT in wastewater and
      surface water samples. Over a period of 12 months, BTri and 5-MeBT concentrations
      in secondary treated wastewater were measured, with the highest BTri and 5-MeBT
      concentrations observed during winter months at 78 ng L(-1) and 21 ng L(-1),
      respectively. The method was also used to assess the removal efficiency of BTri
      and 5-MeBT through an advanced water recycling plant (AWRP). While BTri was more
      persistent than 5-MeBT, both compounds were removed from the AWRP to <10 ng L(-1)
      (BTri) and <2 ng L(-1) (5-MeBT), with reverse osmosis (RO) providing the most
      effective treatment process for their removal. 

PMID- 25564250
TI  - Bobbi Be Best: the development and evaluation of an audio program and discussion
      guide to promote exclusive breastfeeding in Cameroon, Central Africa.
AB  - One risk factor for infant and childhood morbidity is not exclusive breastfeeding
      (EBF) during the first six months of life. Entertainment Education (EE) is a
      communication strategy consisting of placing educational information into
      television, movies, and radio programs. In developing countries this form of
      behavioral change communication has proven effective in addressing health-related
      issues; however, no research has determined if EE is effective in promoting EBF.
      The objective of this research was to develop an EE audio program and discussion
      guide and to determine if a series of four 15-minute episodes and post-listening
      discussion improved knowledge, perceived benefits, self-efficacy, and intention
      and decreased misconceptions and perceived barriers toward EBF in the Kumbo West
      Health District, Cameroon. Pregnant women and their partners were assigned to
      either the control group (N = 116; 74 women, 42 partners) or intervention group
      (N = 148; 99 women, 49 partners) based on expected date of delivery. All control
      and intervention group participants completed a questionnaire prior to listening
      to the first and after the last episode. Pre- and post-listening questionnaires
      were used to determine changes in the EBF knowledge, misconceptions, perceived
      barriers, self-efficacy, and intention variables as a result of exposure to the
      audio program. The Wilcoxon Sign Rank test showed significant improvement in all
      of the variables, except perceived barriers, within the intervention group (p <
      0.05) and the Mann-Whitney test indicated significant differences between the
      control and intervention group in all of the variables (p < 0.05), indicating
      that using an audio program and discussion guide based on the EE model is an
      effective tool for promoting EBF in this setting. The strength of this approach
      is that it goes beyond simply telling women about what constitutes EBF, but
      addresses misconceptions and perceived barriers that may prevent women from
      practicing EBF for six months. 

PMID- 25564251
TI  - Circulating tumour cells and circulating nucleic acids as a measure of tumour
      dissemination in non-metastatic colorectal cancer surgery.
AB  - There is accumulating evidence for circulating tumour cells (CTCs) and
      circulating tumour nucleic acids (ctNAs) as prognostic and predictive biomarkers
      in colorectal cancer. Their role in the perioperative setting is evolving. These
      blood-borne biomarkers can potentially demonstrate tumour dissemination at time
      of colorectal cancer surgery and estimate the completeness of a surgical
      resection. CTCs and circulating ctNA levels at time of surgery, and persistent
      levels post-surgery, may correlate with poorer patient outcomes. These biomarkers
      can be utilised to refine surgical techniques to minimise tumour dissemination
      and determine the need for adjuvant therapy. 

PMID- 25564249
TI  - The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate
      Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive
      Therapy in Malawian Pregnant Women.
AB  - BACKGROUND: The A581 G: mutation in the gene encoding Plasmodium falciparum
      dihydropteroate synthase (dhps), in combination with the quintuple mutant
      involving mutations in both dhps and the gene encoding dihydrofolate reductase
      (dhfr), the so-called sextuple mutant, has been associated with increased
      placental inflammation and decreased infant birth weight among women receiving
      intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) during
      pregnancy. METHODS: Between 2009 and 2011, delivering women without human
      immunodeficiency virus infection were enrolled in an observational study of IPTp
      SP effectiveness in Malawi. Parasites were detected by polymerase chain reaction
      (PCR); positive samples were sequenced to genotype the dhfr and dhps loci. The
      presence of K540 E: in dhps was used as a marker for the quintuple mutant.
      RESULTS: Samples from 1809 women were analyzed by PCR; 220 (12%) were positive
      for P. falciparum. A total of 202 specimens were genotyped at codon 581 of dhps;
      17 (8.4%) harbored the sextuple mutant. The sextuple mutant was associated with
      higher risks of patent infection in peripheral blood (adjusted prevalence ratio
      [aPR], 2.76; 95% confidence interval [CI], 1.82-4.18) and placental blood (aPR
      3.28; 95% CI, 1.88-5.78) and higher parasite densities. Recent SP use was not
      associated with increased parasite densities or placental pathology overall and
      among women with parasites carrying dhps A581 G: . CONCLUSIONS: IPTp-SP failed to
      inhibit parasite growth but did not exacerbate pathology among women infected
      with sextuple-mutant parasites. New interventions to prevent malaria during
      pregnancy are needed urgently.

PMID- 25564252
TI  - Role of microRNA 21 in mesenchymal stem cell (MSC) differentiation: a powerful
      biomarker in MSCs derived cells.
AB  - The significant role of microRNAs (miRNAs) in stem cell development has been
      expansively discussed in recent publications and they are noticed to be involved
      in post transcriptional regulation of gene expression by its affinity towards the
      3'UTR of target mRNA. Since the expression of miR-21 was high in cells that were
      derived from MSCs, recent evidence indicates that miR-21 plays a vital role in
      mesenchymal stem cells (MSCs) differentiation. Despite the fact that miR-21 can
      be considered as a powerful biomarker for MSCs differentiation, the number of
      studies related to the above scenario is very limited. This review highlights the
      recent publications related to the importance of miR-21 specifically in
      differentiation of MSCs. 

PMID- 25564253
TI  - Effect of six insecticides on three populations of Bactrocera (Tetradacus) minax
      (Diptera: Tephritidae).
AB  - The Chinese citrus fruit fly, Bactrocera minax is one of the most economically
      important and aggressive pests threatening the Chinese citrus industry. In order
      to provide some recommendations for the improvement of integrated pest management
      of this species, the authors evaluated the toxicity of 6 insecticides on the
      second stage larvae, fourth stage larvae, and adult flies from multiple
      geographical B. minax populations. In addition, the influences of each pesticide
      on pupation and emergence were examined for one population, from Hanzhong. The 6
      reagents displayed a wide range of toxicity on various stages of B. minax.
      Abamectin and Dichlorphos displayed the highest and lowest toxicities,
      respectively. All of the insecticides had negative effects on pupation and
      emergence of B. minax from Hanzhong, while Chlorpvrifos had the strongest impact
      on pupation, and Phoxim had the strongest influence on emergence. Though Phoxim
      and Chlorpvrifos were both effective, these insecticides belong to the class of
      organophosphorus pesticides, and their use should be reduced in orchards because
      of their high toxicity and long residual period. 

PMID- 25564254
TI  - MYC-mediated synthetic lethality for treatment of hematological malignancies.
AB  - Deregulated c-MYC expression is found in many human malignancies. MYC activation
      induces multiple lineages of hematological malignancies in single Myc transgenic
      mice. MYC inactivation causes tumor regression. MYC is therefore an attractive
      target for cancer treatment. However, little progress has been made in the
      development and application of targeted MYC inactivation in clinical practice. In
      double Myc transgenic mouse models, Myc-driven leukemogenesis and lymphomagenesis
      can be accelerated by transduction of non-MYC oncogenes, leading to dual
      addiction to MYC and the non-MYC oncogenes. Wang et al. (2004) first established
      the concept of MYC-mediated synthetic lethality (MYC-SL). MYC overexpression
      sensitized cells to TRAILand DR5-agonist-induced apoptosis. This suggests that
      MYC-dependent tumor cells may be killed by targeting partner oncogenes of MYC.
      Many small molecule inhibitors (SMIs) have been proven to induce MYC-SL by
      targeting AUK-B, Brd4, CDK1, CHK1, MCL-1, the mTOR/4E-BP1/eIF4E pathway, and
      PIM1/2. Compared with conventional treatment approaches, SMI-induced MYC-SL
      displays highly selective anticancer activity and much lower cytotoxicity to
      normal cells. SMI-induced MYC-SL can reverse eIF4F- and PIM2-induced multiple
      chemoresistance. The combination of an SMI with chemotherapeutic agents can
      elevate chemotherapy efficacy by enhancing chemosensitivity. This combination
      will be a promising novel approach to treating MYC-dependent tumors by inducing
      MYC-SL. 

PMID- 25564255
TI  - Nano-pharmaceutical formulations for targeted drug delivery against HER2 in
      breast cancer.
AB  - Nanotechnology has revolutionized fundamental opportunities for higher specific
      drug delivery with minimum side effects. Since its inception, the goal of
      nanotechnology has been to advance effective and reliable systems for precise
      anti-cancer therapy and diagnosis. To accomplish this goal, bio-conjugation
      strategies of therapeutic agents loaded nanoparticles with monoclonal antibodies
      or their analogues have demonstrated a targeted approach both in vitro and in
      vivo. In this review, we primarily focus on the specific recognition of HER2
      receptors of HER2 overexpressed tumor cells, and evaluate anti-HER2 monoclonal
      antibody as an effective tool for active targeting. Currently, a variety of
      nanoparticle systems are under both preclinical and clinical trials for targeting
      to HER2 positive breast cancer. Different nanotechnology scaffolds including
      liposomes, dendrimers, micelles, polymeric and inorganic nanoparticles that have
      higher flexibility for macromolecular synthesis and versatile functionalizing
      properties have been reviewed in this study. Continuing advances in anti-HER2
      functionalized nanoparticles have good potential to lead to the development of
      nano-therapy against HER2 positive breast cancer. 

PMID- 25564256
TI  - Orbital Conjunctival Cyst Associated With the Superior Rectus-Levator Muscles: A
      Clinicopathologic Study.
AB  - A 55-year-old woman had a right orbital cyst detected incidentally on
      radiographic imaging. The patient's symptoms were mild and included intermittent
      pain and vertical diplopia; the patient was not aware of any visual decline.
      There was a palpable mass beneath the superior orbital rim. Radiographic imaging
      revealed a well-demarcated cystic lesion in the right superior orbit between the
      levator palpebrae superioris and superior rectus muscles. The mass was completely
      excised via a transconjunctival approach. Histopathologic evaluation disclosed a
      conjunctival cyst lined by nonkeratinized squamous epithelium with scattered,
      rare goblet cells. This case combined with 5 other similar reported cases
      suggests that an intermuscular cyst located in the superior rectus-levator
      complex is most likely of congenital embryonic conjunctival origin.

PMID- 25564257
TI  - IgG4-related ophthalmic disease. Part I: background and pathology.
AB  - PURPOSE: To review the current state of knowledge of IgG4-related ophthalmic
      disease (IgG4-ROD). METHODS: A review of the literature and personal experience
      of the authors. RESULTS: IgG4-related disease is a recently recognized
      fibroinflammatory disorder that may affect 1 or more organs. It is characterized
      by lymphoplasmacytic infiltrates with large numbers of IgG4 positive plasma
      cells, storiform fibrosis, obliterative phlebitis, and eosinophil infiltration as
      well as peripheral eosinophilia, and in some cases, elevated serum levels of
      IgG4. These features are not always seen, and the diagnosis should be made by
      integrating clinical, imaging, and histopathological data, with reference to
      recently defined diagnostic criteria. IgG4-ROD forms a significant proportion of
      what has previously been labeled "idiopathic orbital inflammation" or reactive
      lymphoid hyperplasia. Orbital disease may occur alone, at the same time as
      disease elsewhere, or metachronously with systemic disease. Although almost any
      ocular adnexal tissue may be affected, there are several more common recognizable
      patterns of IgG4-ROD: 1) sclerosing dacryoadenitis; 2) enlargement of orbital
      nerves (most commonly the infraorbital nerve) associated with orbital myositis
      and lacrimal gland disease, often in combination with paranasal sinus disease,
      eosinophilia, and systemic involvement; and 3) sclerosing orbital inflammation.
      CONCLUSIONS: Patients presenting with orbital inflammatory lesions should have
      biopsies obtained whenever possible. The examining pathologist should routinely
      look for features of IgG4-ROD, and if found, the patient should be investigated
      for other organ involvement. Early treatment may prevent destructive changes in
      affected tissues.

PMID- 25564258
TI  - IgG4-Related Ophthalmic Disease. Part II: Clinical Aspects.
AB  - PURPOSE: To review the current state of knowledge of IgG4-related ophthalmic
      disease (IgG4-ROD). METHODS: A review of the literature and personal experience
      of the authors. RESULTS: IgG4-related disease is a recently recognized
      fibroinflammatory disorder that may affect 1 or more organs. It is characterized
      by lymphoplasmacytic infiltrates with large numbers of IgG4 positive plasma
      cells, storiform fibrosis, obliterative phlebitis, and eosinophil infiltration as
      well as peripheral eosinophilia, and in some cases, elevated serum levels of
      IgG4. These features are not always seen, and the diagnosis should be made by
      integrating clinical, imaging, and histopathological data, with reference to
      recently defined diagnostic criteria. IgG4-ROD forms a significant proportion of
      what has previously been labeled "idiopathic orbital inflammation" or reactive
      lymphoid hyperplasia. Orbital disease may occur alone, at the same time as
      disease elsewhere, or metachronously with systemic disease. Although almost any
      ocular adnexal tissue may be affected, there are several commoner recognizable
      patterns of IgG4-ROD: (1) sclerosing dacryoadenitis; 2) enlargement of orbital
      nerves (most commonly the infraorbital nerve) associated with orbital myositis
      and lacrimal gland disease, often in combination with paranasal sinus disease,
      eosinophilia, and systemic involvement; and 3) sclerosing orbital inflammation.
      Patients with IgG4-ROD should be investigated and monitored for other organ
      involvement. Some patients with IgG4-related disease may develop lymphoma,
      usually marginal zone lymphoma of mucosa-associated lymphoid tissue type.
      Treatment of IgG4-ROD includes the use of corticosteroids and other
      immunosuppressants. Rituximab has been shown to be very effective. Longer term
      studies on the natural course and treatment of IgG4-ROD are needed. CONCLUSIONS:
      Patients presenting with orbital inflammatory lesions should have biopsies
      obtained whenever possible. The examining pathologist should routinely look for
      features of IgG4-ROD, and if found, the patient should be investigated for other
      organ involvement. Early treatment may prevent destructive changes in affected
      tissues.

PMID- 25564259
TI  - Unilateral Migratory Relapsing Orbital Myositis While on Immunosuppressant
      Therapy: An Uncommon Entity.
AB  - A young healthy female presented with acute onset left ocular pain, restricted
      ocular motility, and binocular diplopia. CT imaging showed left lateral rectus
      myositis that resolved with oral corticosteroids. Two sequential relapses
      occurred subsequently involving the superior rectus-levator complex followed by
      the medial rectus. Biopsy revealed orbital inflammatory disease with lymphocytic
      vasculitis. Detailed systemic work up was normal. The second relapse was seen
      while on long-term oral methotrexate although initial disease remission had been
      achieved with the same drug. A changeover to oral azathioprine was able to
      achieve disease remission after the second relapse. All relapses involved the
      same side and the contralateral orbit was not affected. This report presents the
      curious phenomenon of unilateral migratory relapsing orbital myositis of unknown
      cause that recurred even while on immunosuppressant therapy. It highlights the
      unpredictable nature of this uncommon entity and the challenges faced in managing
      such cases.

PMID- 25564260
TI  - Management of acquired haemophilia A.
AB  - Acquired haemophilia A (AHA) is caused by autoantibody inhibitors of coagulation
      factor VIII (FVIII : C). Recent onset of bleeds and isolated prolongation of the
      activated partial thromboplastin time (aPTT) are characteristic features of the
      disorder. Reduced FVIII : C activity and a detectable FVIII : C inhibitor in the
      Bethesda assay confirm the diagnosis. Patients should be referred to expert
      centres, whenever possible, and invasive procedures with a high risk of bleeding
      must be avoided, until haemostasis has been secured by adequate therapy.
      Bypassing agents capable of inducing sufficient thrombin formation in the
      presence of FVIII : C inhibitors are treatment of choice, including currently
      available recombinant factor VIIa (NovoSevenTM) and activated prothrombin complex
      concentrate (FEIBATM). These agents represent first line therapy to control acute
      or severe bleeds. To eradicate inhibitors, immunosuppressive treatment (IST) is
      indicated in patients with AHA. Glucocorticoids, cytotoxic agents and rituximab
      are most widely used. However, an ideal IST regimen has not been established so
      far. Adverse events of IST, including infections as the foremost cause death, are
      frequent complications in AHA. 

PMID- 25564261
TI  - Temperature dependence of production of structured triacylglycerols in the alga
      Trachydiscus minutus.
AB  - This study describes the identification of regioisomers and enantiomers of
      triacylglycerols of C20 polyunsaturated fatty acids (PUFAs) in the alga
      Trachydiscus minutus cultivated at different temperatures using reversed- and
      chiral-phase liquid chromatography-mass spectrometry. The use of the two
      different phases contributes to ready identification, both qualitative and
      semiquantitative, of regioisomers and enantiomers of triacylglycerols containing
      eicosapentaenoic and arachidonic in the molecule. The ratio of regioisomers and
      enantiomers of triacylglycerols (TAG) depends on the temperature of cultivation;
      with lowering temperature the proportion of the achiral TAG increases and the
      enantiomer ratio diverges from 1:1. 

PMID- 25564262
TI  - Plant metabolite profiles and the buffering capacities of ecosystems.
AB  - In spite of some inherent challenges, metabolite profiling is becoming
      increasingly popular under field conditions. It has been used successfully to
      address topics like species interactions, connections between growth and chemical
      stoichiometry or the plant's stress response. Stress exerts a particularly clear
      impact on plant metabolomes and has become a central topic in many metabolite
      profiling experiments in the fields. In contrast to phytochambers, however,
      external stress is often at least partially absorbed by the environment when
      measuring under field conditions. Such stress-buffering capacities of (agro)
      ecosystems are of crucial interest given the ever-increasing anthropogenic impact
      on ecosystems and this review promotes the idea of using plant metabolite
      profiles for respective measurements. More specifically I propose to use
      parameters of the response of key plant species to a given stress treatment as
      proxies for measuring and comparing stress-buffering capacities of ecosystems.
      Stress response parameters accessible by metabolite profiling comprise for
      example the intensity or duration of the impact of stress or the ability of the
      plant organism to recover from this impact after a given time. Analyses of
      ecosystem stress-buffering capacities may improve our understanding of how
      ecosystems cope with stress and may improve our abilities to predict ecosystem
      changes. 

PMID- 25564263
TI  - Comparative anti-proliferative activity of some new 2-(arylazo)phenolate
      palladium (II) complexes and cisplatin against some human cancer cell lines.
AB  - In this study, we report the synthesis of four 2-(arylazo)phenol-Pd(II) complexes
      and their anti-proliferative property against the human lung cancer (A549),
      cervical cancer (HeLa), and ovarian teratocarcinoma (PA-1) cell lines with
      cisplatin as the gold standard. One of the complexes, [Pd(L(2))2], induced robust
      apoptosis in all the chosen cells, as revealed by annexin-V-positive/propidium
      iodide dual staining, increased sub-G1 cell cycle population, and significant
      morphological changes in the treated cells. The Pd complex inflicted
      mitochondrial dysfunction leading to mitochondrial membrane potential loss,
      reactive oxygen species generation and release of cytosolic cytochrome c that
      activated caspase-9 and caspase-3 proteins which finally caused programmed cell
      death. 

PMID- 25564264
TI  - Addition of zygomatic arch resection in decompressive craniectomy.
AB  - Decompressive craniectomy (DC) is a surgical option in managing uncontrolled
      raised intracranial pressure refractory to medical therapy. The authors evaluate
      the addition of zygomatic arch (ZA) resection with standard DC and analyze the
      resulting increase in brain volume using three-dimensional volumetric CT scans.
      Measurements of brain expansion dimension morphometrics from CT images were also
      analyzed. Eighteen patients were selected and underwent DC with ZA resection. The
      pre- and post-operative CT images were analyzed for volume and dimensional
      changes. CT images of 29 patients previously operated on at the same center were
      retrieved from the picture archiving and communication system (PACS) and were
      similarly studied. The findings obtained from the two groups were compared and
      analyzed. Analysis from three-dimensional CT volumetric techniques revealed an
      significant increase of 27.97ml (95% confidence interval [CI]: 39.98-180.36;
      p=0.048) when compared with standard DC. Brain expansion analysis of maximum
      hemicraniectomy diameter revealed a mean difference of 0.82cm (95% CI: 0.25-1.38;
      p=0.006). Analysis of the ratio of maximum hemicraniectomy diameter to maximum
      anteroposterior diameter gave a mean difference of 0.04 (95% CI: 0.05-0.07;
      p=0.026). The addition of ZA resection to standard DC may prove valuable in terms
      of absolute brain volume gain. This technique is comparable to other maneuvers
      used to provide maximum brain expansion in the immediate post-operative period.

PMID- 25564266
TI  - Association between matrix metalloproteinase-3 gene polymorphism and moyamoya
      disease.
AB  - Genetic factors play an important role in the etiology and pathogenesis of
      moyamoya disease (MMD). Recently, several studies suggested the decreased
      expression of matrix metalloproteinase-3 (MMP3) was associated with an increased
      risk of MMD. This case-control study was performed to examine the association
      between MMP3 polymorphisms and the risk of MMD, comparing 86 Han Chinese MMD
      patients and 86 controls. We further conducted a meta-analysis, combining our
      results with all previous studies to provide a more precise estimate of this
      association. In our case-control study, MMP3 6A/6A (odds ratio [OR]=1.93, 95%
      confidence interval [CI] 1.00-3.72; p=0.05) and 6A allele frequencies (OR=1.78,
      95%CI 1.00-3.14; p=0.05) in the MMD group were significantly higher than those in
      the control group. In the additional meta-analysis, only two other studies were
      identified. Meta-analysis with a total of 796 patients revealed 6A allele and
      6A/6A genotype significantly increased the risk of MMD (OR=1.64, 95% CI 1.26
      2.13, p=0.0002 and OR=1.79, 95% CI 1.32-2.42, p=0.0002, respectively). To confirm
      this finding, an additional analysis should be performed using a larger sample
      size. Moreover, larger and well-designed multicentric studies based on different
      races should be performed to evaluate the racial difference. 

PMID- 25564265
TI  - Transient pupillary dilation following local papaverine application in
      intracranial aneurysm surgery.
AB  - Isolated cases of transient pupillary changes after local intracisternal
      papaverine administration during aneurysm surgery have been reported. This study
      aimed to determine the prevalence and factors associated with this phenomenon. We
      assessed a total of 103 consecutive patients who underwent craniotomy for
      cerebral aneurysm clipping for the presence of postoperative pupillary dilation
      (mydriasis) after intracisternal papaverine administration. Univariate and
      multivariate logistic regression were conducted to evaluate the association of
      mydriasis with patient age, sex, duration of surgery, and aneurysm location. We
      observed either ipsilateral or bilateral pupillary dilation in the immediate
      postoperative period in nine out of 103 patients (8.7%). This phenomenon was not
      associated with patient age or sex. There was a trend towards positive
      correlation with aneurysms located at the anterior communicating artery (odds
      ratio 3.76, p=0.10), and a negative correlation with the duration of surgery
      (odds ratio 0.57, p=0.08). All pupillary dilation resolved within several hours,
      and the onset and resolution were consistent with the half-life of papaverine. To
      our knowledge, this represents the largest study of posteropative pupillary
      changes due to papaverine. The current findings are consistent with the small
      number of prior case reports of transient pupillary changes after papaverine
      administration and appear to reflect the local anesthetic action of papaverine on
      the oculomotor nerve. 

PMID- 25564267
TI  - Agraphia caused by acute right parietal infarction.
AB  - Injury in the dominant language hemisphere typically leads to agraphia, however
      we report a patient with agraphia after injury to the right angular gyrus. A 71
      year-old Korean woman presented with the complaint of an inability to write for
      the last 7 days. The patient had been illiterate for most of her life, but had
      started learning to write Hangul, the Korean alphabet, at a welfare center 3
      years ago. On language screening she was unable to write although she could read,
      and other language functions showed no abnormalities. Brain MRI showed acute
      infarction in the right angular gyrus. Her writing patterns displayed features of
      surface agraphia, indicative of phoneme-to-grapheme conversion with phonetic
      writing of targets. Additionally, she manifested visual errors. A functional MRI
      indicated that her left hemisphere was language dominant. This patient
      experienced agraphia resulting from pure impairment of visuo-constructive
      function after acute infarction in the right angular gyrus.

PMID- 25564268
TI  - Isolated astasia manifested by acute infarct of the anterior corpus callosum and
      cingulate gyrus.
AB  - Astasia, the inability to stand and walk, in the absence of weakness or ataxia,
      is uncommon and unique. This syndrome is easy to misdiagnose as
      vestibulocerebellar disease. We report a patient with anterior callosal and
      cingulate infarction presenting as isolated astasia. A 65-year-old hypertensive
      man was admitted to our hospital with marked truncal instability. On neurological
      examination, he was unable to stand and walk independently. When asked to stand
      up from a sitting position, he had to grasp something nearby to propel himself
      upwards, and could not use his axial muscles. He collapsed when support was
      withdrawn. The patient showed no signs of amnesia, aphasia, apraxia or
      hemiasomatognosia. Diffusion weighted imaging at 3days after onset demonstrated
      an acute infarct in the anterior part of the right-sided corpus callosum and
      cingulate gyrus. Magnetic resonance angiography revealed an occlusion of the
      right anterior cerebral artery. We discuss the possible mechanisms of astasia due
      to anterior callosal and cingulate infarction. 

PMID- 25564269
TI  - A novel mechanism of toxic injury to the Papez circuit from chemotherapy.
AB  - Toxic effects of chemotherapy delivered via Ommaya reservoir include pericatheter
      necrosis and toxic leukoencephalopathy. Imaging evidence of toxicity is often
      asymptomatic, but can be clinically consequential. A young patient, treated for
      cerebrospinal fluid relapse of acute lymphoblastic leukemia with methotrexate and
      cytarabine via Ommaya reservoir, presented with acute deterioration of short-term
      memory. MRI demonstrated extra-ventricular Ommaya catheter position and typical
      methotrexate-induced changes in the deep white matter, but also signal alteration
      in the forniceal columns and mammillary bodies, components of the Papez circuit.
      This case presents a novel mechanism of chemotherapy-induced neurotoxicity
      associated with extra-ventricular Ommaya catheter position. Specifically, the
      clinical and imaging findings suggest that extra-ventricular Ommaya catheter
      position may lead to a direct methotrexate-induced toxicity to the Papez circuit.
      This provides further clinical evidence of the function of the circuit. The
      possibility that this patient received a supratherapeutic dose of methotrexate
      may explain why this presentation with profound memory impairment is not more
      common. However, this case also provides a potential explanation for patients who
      receive standard dose chemotherapy via extra-ventricular Ommaya catheter and
      develop milder memory loss.

PMID- 25564271
TI  - Names of infamy: tainted eponyms.
AB  - The use of eponyms is controversial. A distinction must be made between those
      doctors and scientists after whom disorders and syndromes are named in honour of
      their discoveries, and those whose discoveries were made as a result of
      maltreatment of defenceless prisoners, utilizing specimens from victims of Nazi
      extermination policies, and euthanasia victims of racial policies. The second
      group of scientists should have their names expunged from the historical record,
      and their deeds brought to the attention of their colleagues. We are not however
      advocating the abolition of eponyms in general, only tainted ones. 

PMID- 25564270
TI  - In-hospital outcomes of thrombolysis for acute ischemic stroke in patients with
      primary brain tumors.
AB  - Data on thrombolysis outcomes in patients with primary brain tumors are limited.
      Our aim was to study stroke outcomes following thrombolysis in these patients in
      a population-based study. Patients with acute ischemic stroke who received
      thrombolysis were identified from the 2002-2011 USA Nationwide Inpatient Sample.
      We compared demographics, comorbidities, and outcomes between primary brain tumor
      associated strokes (BTS) and non-brain tumor associated strokes (NBTS). The main
      outcomes were inpatient mortality, home discharge and intracranial hemorrhage
      (ICH) rate. Of the 124,083 thrombolysis-treated stroke patients, 416 (0.34%) had
      brain tumors. In adjusted analysis, inpatient mortality (odds ratio [OR]: 0.98;
      95% confidence interval [CI]: 0.77-1.26, p=0.918), rate of home discharge (OR:
      1.15; 95% CI: 0.87-1.53, p=0.40) and rate of ICH (OR: 0.94; 95% CI: 0.62-1.44,
      p=0.801) were similar between BTS and NBTS. Analysis of brain tumor subtypes
      showed that compared to NBTS, malignant BTS were independently associated with
      higher in-hospital mortality (OR: 2.51; 95% CI: 1.66-3.79, p<0.001), lower home
      discharge (OR: 0.36, 95% CI: 0.18-0.72, p=0.004), and increased risk of ICH (OR:
      2.33, 95% CI: 1.49-3.65, p<0.001). Additionally, among the BTS, intraparenchymal
      location of tumor was associated with higher mortality (OR: 2.51; 95% CI: 1.20
      5.23, p=0.014) and lower home discharge (OR: 0.26; 95% CI: 0.13-0.53, p<0.001).
      Thrombolytic therapy for acute stroke appears to be safe in patients with primary
      brain tumors, with similar rates of ICH. Malignant BTS have worse outcomes, while
      benign BTS have outcomes comparable to NBTS. Careful consideration of tumor
      pathology may aid selection of patients with poor thrombolysis outcomes. 

PMID- 25564272
TI  - Decompressive craniectomy for arteriovenous malformation-related intracerebral
      hemorrhage.
AB  - Arteriovenous malformation (AVM)-related intracerebral hemorrhage (ICH) is the
      cause of approximately 2-3% of ICH and is an important factor in the significant
      morbidity and mortality in patients with AVM. Decompressive craniectomy (DC) is a
      surgical procedure to relieve malignant elevation of intracranial pressure. The
      use of DC to treat patients with AVM-ICH has been much less common. The present
      study describes our experience with DC for AVM-ICH and discusses the safety of
      this procedure. The present retrospective analysis compared 12 consecutive
      patients treated with DC for AVM-ICH with 23 patients treated with DC for
      hypertensive ICH. Nine patients were male and three were female, aged from 11 to
      53 years (mean, 31.7 years). Hematoma volumes ranged from 50 to 106 ml (mean,
      75.8 ml). The outcomes were good recovery in one patient, moderate disability in
      three, severe disability in seven, and vegetative state in one. Complications
      after DC included subdural hygroma in four patients, hydrocephalus in one,
      intracranial infection in two, and intracranial hemorrhage in one. No significant
      difference was found in the incidence of complications between DC for large AVM
      ICH and DC for hypertensive ICH. In conclusion, the present study found no
      significant difference in the incidence of complications between DC for large AVM
      ICH and DC for hypertensive ICH. Further investigations including a prospective
      randomized trial are needed to confirm the safety and efficacy of DC for the
      treatment of large AVM-ICH.

PMID- 25564273
TI  - Reduced expression of microRNA-134 correlates with malignancy and poor prognosis
      in human glioma.
AB  - MicroRNA-134 (miR-134) has been demonstrated to be dysregulated in glioma
      tissues. However, its clinical significance in this tumor type has not been fully
      elucidated. This study was designed to explore the association of miR-134
      expression with clinicopathological features and prognosis in human glioma. Using
      real-time quantitative polymerase chain reaction, miR-134 expression was detected
      in 162 glioma specimens with various World Health Organization (WHO) grades and
      compared to the expression in 36 normal brain tissue samples. Glioma tissues
      exhibited significantly reduced expression of miR-134 (mean 2.15 +/- standard
      deviation 0.82 versus 4.37 +/- 1.16, p<0.001) compared with normal brain tissues.
      In addition, miR-134 expression was notably associated with WHO grade (p<0.001)
      and Karnofsky Performance Scale score (KPS; p=0.02) in glioma tissues. Low miR
      134 expression occurred more frequently in glioma tissues with high WHO grades
      and low KPS scores. In univariate analysis, both progression-free survival (PFS)
      and overall survival (OS) of glioma patients with low miR-134 expression were
      significantly shorter than those with high miR-134 expression (both p<0.001).
      Additionally, glioma patients with high WHO grades, low KPS scores and subtotal
      resection attained significantly poorer PFS (p<0.001, 0.02 and 0.01,
      respectively) and OS (p<0.001, 0.01 and 0.01, respectively). In multivariate
      analysis, miR-134 expression, WHO grade, KPS score and extent of resection were
      identified as the independent prognostic factors for both PFS and OS.
      Collectively, our data prove that the reduced expression of miR-134 may predict
      aggressive progression and poor prognosis in human gliomas. miR-134 may represent
      both a prognostic marker and a novel therapeutic target for this malignancy.

PMID- 25564274
TI  - Novel application of pre-operative vertebral body embolization to reduce
      intraoperative blood loss during a three-column spinal osteotomy for non
      oncologic spinal deformity.
AB  - Three column osteotomies (3CO) of the lumbar spine are powerful corrective
      procedures used in the treatment of kyphoscoliosis. Their efficacy comes at the
      cost of high reported complication rates, notably significant estimated blood
      loss (EBL). Previously reported techniques to reduce EBL have had modest
      efficacy. Here we describe a potential technique to decrease EBL during pedicle
      subtraction osteotomy (PSO) of the lumbar spine by means of pre-operative
      vertebral body embolization - a technique traditionally used to reduce blood loss
      prior to spinal column tumor resection. We present a 62-year-old man with
      iatrogenic kyphoscoliosis who underwent staged deformity correction. Stage 1
      involved thoracolumbar instrumentation followed by transarterial embolization of
      the L4 vertebral body through bilateral segmental arteries. A combination of
      polyvinyl alcohol particles and Gelfoam (Pfizer, New York, NY, USA) were used.
      Following embolization there was decreased angiographic blood flow to the small
      vessels of the L4 vertebral body, while the segmental arteries remained patent.
      Stage 2 consisted of an L4 PSO and fusion. The EBL during the PSO procedure was
      1L, which compared favorably to that during previous PSO at this institution as
      well as to quantities reported in previous literature. There have been no short
      term (5 month follow-up) complications attributable to the vertebral body
      embolization or surgical procedure. Although further investigation into this
      technique is required to better characterize its safety and efficacy in reducing
      EBL during 3CO, we believe this patient illustrates the potential utility of pre
      operative vertebral embolization in the setting of non-oncologic deformity
      correction surgery.

PMID- 25564275
TI  - The level of Alzheimer-associated neuronal thread protein in urine may be an
      important biomarker of mild cognitive impairment.
AB  - Increased levels of Alzheimer-associated neuronal thread protein (AD7c-NTP) are
      often detected in urine in the early course of Alzheimer's disease (AD), which
      makes it a promising biomarker for AD. However, whether the concentration of
      urinary AD7c-NTP is increased in patients with mild cognitive impairment (MCI)
      remains unclear. The aim of this study was to explore the value of urinary AD7c
      NTP to assist in the diagnosis of cognitive impairment by comparing differences
      in urinary AD7c-NTP among normal controls, MCI patients and AD patients. One
      hundred and seventy patients from the Xuan wu Hospital, Capital Medical
      University were divided into three groups according to their clinical diagnosis:
      an AD group (n=45), an MCI group (n=60) and a normal group (n=65). The Mini
      Mental State Examination and the Montreal Cognitive Assessment scale were used to
      screen for the diagnosis of AD and MCI, and patients met the diagnostic criteria
      of the National Institute of Neurological Disorders and Stroke and the
      Alzheimer's Disease and Related Disorders Association. The level of urinary AD7c
      NTP was determined using the enzyme-linked immunosorbent assay method. The
      urinary levels of AD7c-NTP in the AD group (median 2.14 [range 0.49-6.39] ng/ml)
      and the MCI group (median 1.57 [range 0.4-4.15] ng/ml) were significantly higher
      than those of the normal group (median 0.53 [range 0.04-2.07] ng/ml). To our
      knowledge our study is the first to show that the level of urinary AD7c-NTP in
      MCI patients is higher than in healthy people, which suggests that the level of
      urinary AD7c-NTP may be an important biomarker for early diagnosis of MCI.

PMID- 25564277
TI  - Methodological caveats in the environmental modelling and projections of climate
      niche for ticks, with examples for Ixodes ricinus (Ixodidae).
AB  - Interest is increasing in inferring the climate niche of health-threatening
      arthropods and projecting such inferences onto a territory. This approach is
      intended to predict the range of tick distribution and to elucidate tick
      responses to climate scenarios, using so-called correlative models. However, some
      methodological gaps might prevent achieving an adequate background for hypothesis
      testing. We explore, describe, and illustrate these procedural inaccuracies with
      examples focused on the tick Ixodes ricinus and examine how these factors might
      affect modelling outcomes. Our aim was to develop a backdrop of rules for
      developing reliable models for these parasites. The use of partial sets of tick
      occurrences might produce unreliable associations with climate because the
      algorithms cannot capture the complete niche with which the tick is associated.
      Reliability measures of the model cannot detect these inaccuracies, and
      undesirable estimations of the niche will prevail in the chain of further
      calculations. The use of inadequate environmental variables (covariates) may lead
      to inflation of the results of the model through two statistical processes,
      autocorrelation and colinearity. We demonstrate the high colinearity existing in
      climate products derived from interpolation of climate recording stations. Our
      explicit advice is to focus on the training of climate models with satellite
      derived information of climate, from which colinearity of the time series has
      been removed through a harmonic regression. We also emphasize the high
      uncertainty if inference about the climate niche is expanded into different time
      slices, like projected climate scenarios. 

PMID- 25564276
TI  - Comparative speed of efficacy against Ctenocephalides felis of two oral
      treatments for dogs containing either afoxolaner or fluralaner.
AB  - A study was designed to compare the efficacy of NexGard((r)) and BravectoTM, 2
      recently introduced oral ectoparasiticides containing isoxazolines, against fleas
      (Ctenocephalides felis) on dogs. Twenty-four healthy dogs, weighing 9.2 kg to
      28.6 kg, were included in this parallel group design, randomized, and controlled
      efficacy study. On Day -1, the 24 dogs were allocated to 3 study groups:
      untreated control; Nexgard((r)) treated and BravectoTM treated. The treatments
      were administered on Days 0, 28 and 56 for Nexgard((r)) (labelled for monthly
      administration), and once on Day 0 for BravectoTM (labelled for a 12 week use).
      Flea infestations were performed weekly with 100 adult unfed C. felis on each dog
      from Days 42 to 84. Fleas were counted and re-applied at 6 and 12 h post
      infestation and removed and counted 24 h post-infestation. The arithmetic mean
      flea count for the untreated group ranged from 62.9 to 77.6 at 24 h post
      infestation, indicating vigorous flea challenges on all assessment days. Both the
      Nexgard((r)) and BravectoTM treated groups had statistically significantly
      (p<0.05) less fleas compared to the untreated group on all assessment time points
      and days. Significantly fewer fleas were recorded for NexGard((r)) treated dogs
      compared to BravectoTM treated dogs at 6 h post-infestation on Day 56, 63, 70, 77
      and 84 and at 12 h post-infestation on Days 70 and 84. No statistically
      significant (p<0.05) differences were recorded between the treated groups at 24 h
      post-infestation. Efficacies recorded 6 h post-infestation for Nexgard((r))
      ranged from 62.8% (Day 49) to 97.3% (Day 56), and efficacies ranged from 94.1%
      (Day 49) to 100% (Days 42, 56, 70 and 84) at 12 h post-infestation. Efficacies
      recorded for BravectoTM ranged from 45.1% (Day 84) to 97.8% (Day 42) at 6 h post
      infestation, and from 64.7% (Day 84) to 100% (Days 42 and 56) at 12 h post
      infestation. Efficacies observed at 24 h were 100% for both products during the
      study except 99.6% on Day 84 for BravectoTM.

PMID- 25564278
TI  - A comparative analysis of coverage decisions for outpatient pharmaceuticals:
      evidence from Denmark, Norway and Sweden.
AB  - This study analyses the reasons for differences and similarities in coverage
      recommendations for outpatient pharmaceuticals in Denmark, Norway and Sweden,
      following HTA appraisals. A comparative analysis of all outpatient drug
      appraisals carried out between January 2009 and December 2012, including an
      analysis of divergent coverage recommendations made by all three countries was
      performed. Agreement levels between HTA agencies were measured using kappa
      scores. Consultations with stakeholders in the three countries were carried out
      to complement the discussion on HTA processes and reimbursement outcomes.
      Nineteen outpatient drug-indication pairs appraised in each of the three
      countries were identified, of which 6 pairs (32%) had divergent coverage
      recommendations. An uneven distribution of coverage recommendations was observed,
      with the highest overlap in appraisals between Norway and Sweden (free-marginal
      kappa 0.89). Similarities were found in priority setting principles, mode of
      appraisal and reasoning for coverage recommendations. The study shows that health
      economic evaluation is less prominent or explicit in outpatient drug appraisals
      in Denmark than in Norway and Sweden, that all three countries could benefit from
      improved communication between appraisers and manufacturers, and that final
      coverage recommendations rely on factors other than safety, comparative efficacy
      or cost-effectiveness. 

PMID- 25564280
TI  - The essential functions.

PMID- 25564279
TI  - The effects of economic sanctions on disease specific clinical outcomes of
      patients with thalassemia and hemophilia in Iran.
AB  - BACKGROUND: The sanctions applied by both the USA and the EU against Iran do not
      formally ban the exports of medicines; in practice, however, patients are
      experiencing great difficulty in securing the treatment. This article documents
      the impact of international sanctions on patients with thalassemia and hemophilia
      in southern Iran. METHODS: This survey examined the specific effects of external
      sanctions on the access of patients to their treatment between 2009 and 2012 from
      the point of view of patients with thalassemia (n=69) and congenital coagulation
      disorders (n=40) as well as related physicians (n=20). Also, clinical
      manifestation and laboratory data of patients were compared in the same period.
      RESULTS: Access to deferoxamine and Exjade as iron chelators in patients with
      thalasseamia, respectively, declined by almost 70% and half over this period. In
      addition, access to lyophilized coagulation factor VIII concentrate in hemophilia
      A dramatically dropped from 96.7% in 2009 to 3.3% in 2012. The clinical results
      showed a significant deterioration of arthropathy (P<0.001) in hemophiliac
      patients and a significant increase in serum ferritin levels in thalassemia
      patients (P=0.036). CONCLUSION: Sanctions had significant effect on public health
      on patients with thalassemia and hemophilia.

PMID- 25564281
TI  - Smokers' attitudes and support for e-cigarette policies and regulation in the
      USA.
AB  - BACKGROUND: In April 2014, the Food and Drug Administration (FDA) proposed a rule
      to extend its tobacco regulatory authority to e-cigarettes, which have been
      unregulated and growing in use since their 2006-2007 US introduction. The FDA
      will issue a final rule based on comments and data received from researchers,
      tobacco companies and the public. We aimed to present data about current smokers'
      awareness of and attitudes towards potential e-cigarette regulation and various
      policies in the USA. METHODS: We conducted a cross-sectional online e-cigarette
      focused survey of 519 adult current smokers in April 2014, before the FDA's
      proposed rule was announced. Participants were recruited from a private research
      panel (GFK's Knowledge Networks) designed to be representative of the US
      population. RESULTS: The majority of respondents (62.5%) did not know that e
      cigarettes are unregulated by the FDA but agreed that e-cigarettes should be
      regulated by the FDA for safety and quality (83.5%), carry warning labels about
      their potential risks (86.6%) and have the same legal age of sale as other
      tobacco (87.7%). Support was similarly high among current e-cigarette users.
      Support was substantial though lower overall for policies to restrict e-cigarette
      indoor use (41.2%), flavouring (44.3%) and advertising (55.5%), and was
      negatively associated with current e-cigarette use. CONCLUSIONS: Support for many
      e-cigarette regulatory policies is strong among smokers, including for policies
      that the FDA has recently proposed and potential future regulations. States
      considering indoor e-cigarette restrictions should know that a substantial number
      of current smokers support such regulations.

PMID- 25564283
TI  - Tobacco product prices before and after a statewide tobacco tax increase.
AB  - BACKGROUND: In 2013, the State of Minnesota Legislature passed a tobacco tax
      increase that increased the combined cigarette excise and sales tax by US$1.75
      (from US$1.60 to US$3.35) and increased the tax on non-cigarette tobacco products
      from 70% to 95% of the wholesale price. The current study explores the change in
      tobacco prices in retail locations and whether the tax increase was fully passed
      to consumers. METHODS: An observational study of tobacco retail prices was
      performed in a sample of 61 convenience stores in Minnesota, North Dakota, South
      Dakota and Wisconsin. Six rounds of data were collected between May 2013 and
      January 2014. In each round, purchases were made at the same stores for the same
      four tobacco products (Camel Blue cigarettes, Marlboro Gold cigarettes, Grizzly
      Wintergreen moist smokeless tobacco and Copenhagen Wintergreen moist smokeless
      tobacco). RESULTS: For all studied tobacco products, prices in Minnesota
      increased significantly after the tax increase (Round 1-Round 6). After
      controlling for price changes in neighbouring states, the average price
      difference in Minnesota for the two cigarette brands increased by US$1.89 and
      US$1.81, which are both more than the US$1.75 tax increase. For moist smokeless,
      the average price difference increased by US$0.90 and US$0.94. Significant price
      changes were not observed in the comparison states. After the introduction of the
      minimum moist smokeless tax, a significantly higher proportion of Minnesota
      stores offered price promotions on smokeless tobacco. CONCLUSIONS: A large
      tobacco tax resulted in an average retail cigarette price exceeding the tax,
      suggesting the industry over-shifted the cigarette tax increase to consumers in
      Minnesota. The findings support the known public health benefit of tobacco tax
      increases while highlighting the need for additional information about how, or
      if, tobacco companies use price promotions to blunt the impact of tax increases.

PMID- 25564282
TI  - Testing warning messages on smokers' cigarette packages: a standardised protocol.
AB  - PURPOSE: Lab experiments on cigarette warnings typically use a brief one-time
      exposure that is not paired with the cigarette packs smokers use every day,
      leaving open the question of how repeated warning exposure over several weeks may
      affect smokers. This proof of principle study sought to develop a new protocol
      for testing cigarette warnings that better reflects real-world exposure by
      presenting them on cigarette smokers' own packs. METHODS: We tested a cigarette
      pack labelling protocol with 76 US smokers ages 18 and older. We applied graphic
      warnings to the front and back of smokers' cigarette packs. RESULTS: Most smokers
      reported that at least 75% of the packs of cigarettes they smoked during the
      study had our warnings. Nearly all said they would participate in the study
      again. Using cigarette packs with the study warnings increased quit intentions
      (p<0.05). CONCLUSIONS: Our findings suggest a feasible pack labelling protocol
      with six steps: (1) schedule appointments at brief intervals; (2) determine
      typical cigarette consumption; (3) ask smokers to bring a supply of cigarette
      packs to study appointments; (4) apply labels to smokers' cigarette packs; (5)
      provide participation incentives at the end of appointments; and (6) refer
      smokers to cessation services at end of the study. When used in randomised
      controlled trials in settings with real-world message exposure over time, this
      protocol may help identify the true impact of warnings and thus better inform
      tobacco product labelling policy. CLINICAL TRIAL NUMBER: NCT02247908.

PMID- 25564284
TI  - Assessing tobacco regulation: moving beyond economists.

PMID- 25564286
TI  - Consumer surplus and cost-benefit analysis of tobacco use in countries in the
      earlier stages of the tobacco epidemic.

PMID- 25564285
TI  - Smoking status, nicotine dependence and happiness in nine countries of the former
      Soviet Union.
AB  - BACKGROUND: The US Food and Drug Administration has established a policy of
      substantially discounting the health benefits of reduced smoking in its
      evaluation of proposed regulations because of the cost to smokers of the supposed
      lost pleasure they suffer by no longer smoking. This study used data from nine
      countries of the former Soviet Union (fSU) to explore this association in a
      setting characterised by high rates of (male) smoking and smoking-related
      mortality. METHODS: Data came from a cross-sectional population-based study
      undertaken in 2010/2011 in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan,
      Kyrgyzstan, Moldova, Russia and Ukraine. Information was collected from 18 000
      respondents aged >=18 on smoking status (never, ex-smoking and current smoking),
      cessation attempts and nicotine dependence. The association between these
      variables and self-reported happiness was examined using ordered probit
      regression analysis. RESULTS: In a pooled country analysis, never smokers and ex
      smokers were both significantly happier than current smokers. Smokers with higher
      levels of nicotine dependence were significantly less happy than those with a low
      level of dependence. CONCLUSIONS: This study contradicts the idea that smoking is
      associated with greater happiness. Moreover, of relevance for policy in the fSU
      countries, given the lack of public knowledge about the detrimental effects of
      smoking on health but widespread desire to quit reported in recent research, the
      finding that smoking is associated with lower levels of happiness should be
      incorporated in future public health efforts to help encourage smokers to quit by
      highlighting that smoking cessation may result in better physical and emotional
      health.

PMID- 25564287
TI  - One of several 'toys' for smoking: young adult experiences with electronic
      cigarettes in New York City.
AB  - OBJECTIVE: This qualitative research explores the use of electronic cigarettes
      and other similar 'vapor' delivery devices among young adults in New York City.
      METHODS: We employed 17 focus groups followed by 12 semistructured interviews to
      understand the beliefs, opinions and practices related to the use of electronic
      cigarettes among young adult smokers (N=87). RESULTS: Participants were mainly
      daily (52%) and non-daily (41%) smokers. While experimentation with electronic
      cigarette devices was frequently reported, participants related an overall lack
      of information about the devices and what they did know often reflected messages
      in e-cigarette marketing campaigns. Participants also used their own bodily
      sensations as a way to gauge potential risks and benefits of the products.
      Finally, young adults, steeped in a culture of personal technologies, perceived e
      cigarettes as one more 'toy' among other technologies integrated into their
      everyday lives. DISCUSSION: E-cigarettes were also frequently used with other
      tobacco products, including conventional cigarettes. Our research indicates that
      public health campaigns may be needed to counter current industry marketing and
      inform the public that electronic cigarettes are currently unregulated,
      understudied and contain toxicants and carcinogens.

PMID- 25564289
TI  - A smart pH-switchable luminescent hydrogel.
AB  - Here we report a novel example of a luminescent hydrogel, which is formed from
      silent individual molecules simply by altering the pH of the system. Formation of
      the emissive nanostructure is fully and repeatedly reversible. This hydrogel,
      with switchable luminescence, can potentially be used as a nano pH sensor. 

PMID- 25564291
TI  - The influence of DNA shape fluctuations on fluorescence resonance energy transfer
      efficiency measurements in nucleosomes.
AB  - Fluorescence resonance energy transfer (FRET) measurements allow one to observe
      site exposure in nucleosomes, i.e. the transient unwrapping of a part of the
      wrapped DNA from the histone octamer. In such experiments one can typically
      distinguish between a closed state and an open state but in principle one might
      hope to detect several states, each corresponding to a certain number of open
      binding sites. Here we show that even in an ideal FRET setup it would be hard to
      detect unwrapping states with intermediate levels of FRET efficiencies. As the
      unwrapped DNA molecule, modelled here as a wormlike chain, has a finite
      stiffness, shape fluctuations smear out FRET signals completely from such
      intermediate states. 

PMID- 25564288
TI  - Emotional reaction facilitates the brain and behavioural impact of graphic
      cigarette warning labels in smokers.
AB  - BACKGROUND: Warning labels on cigarette packages are an important venue for
      information about the hazards of smoking. The 2009 US Family Smoking Prevention
      and Tobacco Control Act mandated replacing the current text-only labels with
      graphic warning labels. However, labels proposed by the Food and Drug
      Administration (FDA) were challenged in court by the tobacco companies, who
      argued successfully that the proposed labels needlessly encroached on their right
      to free speech, in part because they included images of high emotional salience
      that indiscriminately frightened rather than informed consumers. METHODS: We used
      functional MRI to examine the effects of graphic warning labels' emotional
      salience on smokers' brain activity and cognition. Twenty-four smokers viewed a
      random sequence of blocks of graphic warning labels that have been rated high or
      low on an 'emotional reaction' scale in previous research. RESULTS: We found that
      labels rated high on emotional reaction were better remembered, associated with
      reduction in the urge to smoke, and produced greater brain response in the
      amygdala, hippocampi, inferior frontal gyri and the insulae. CONCLUSIONS:
      Recognition memory and craving are, respectively, correlates of effectiveness of
      addiction-related public health communications and interventions, and amygdala
      activation facilitates the encoding of emotional memories. Thus, our results
      suggest that emotional reaction to graphic warning labels contributes to their
      public health impact and may be an integral part of the neural mechanisms
      underlying their effectiveness. Given the urgency of the debate about the
      constitutional risks and public health benefits of graphic warning labels, these
      preliminary findings warrant consideration while longitudinal clinical studies
      are underway.

PMID- 25564290
TI  - Occupational exposure to wood dust and risk of lung cancer in two population
      based case-control studies in Montreal, Canada.
AB  - BACKGROUND: Wood dust is one of the oldest and one of the most common
      occupational exposures in the world. The present analyses examine the effect of
      lifetime exposure to wood dust in diverse occupational settings on lung cancer
      risk. METHODS: We conducted two population-based case-control studies in
      Montreal: Study I (1979-1986) included 857 cases and two sets of controls (533
      population and 1349 cancer controls), and Study II (1996-2001) comprised 736
      cases and 894 population controls. Detailed job histories were obtained by
      interview and each job was evaluated by expert chemist-hygienists to estimate the
      likelihood and level of exposure to many substances, one of which was wood dust.
      Odds ratios (ORs) were computed in relation to different indices of exposure to
      wood dust, adjusting for several covariates including smoking. Three datasets
      were analysed: Study I with population controls, Study I with cancer controls,
      and Study II. RESULTS: The most frequently exposed occupations in our study
      population were in construction, timber and furniture making industries. We found
      increased risks of lung cancer for substantial cumulative exposure to wood dust
      in Study I with cancer controls, (OR = 1.4: 95% confidence interval 1.0;-2.0) and
      in Study II (OR = 1.7: 95% confidence interval 1.1-2.7). There were no excess
      risks of lung cancer in any of the three datasets among workers whose cumulative
      exposure was not substantial. These tendencies held equally within strata of low
      smokers and heavy smokers. CONCLUSION: There was evidence of increased risk of
      lung cancer among workers with substantial cumulative exposure to wood dust.

PMID- 25564292
TI  - Capture and surveillance of quad-bike (ATV)-related injuries in administrative
      data collections.
AB  - Identifying quad-bike-related injuries in administrative data collections can be
      problematic. This study sought to determine whether quad-bike-related injuries
      could be identified in routinely collected administrative data collections in New
      South Wales (NSW), Australia, and to determine the information recorded according
      to World Health Organization (WHO) injury surveillance guidelines that could
      assist injury prevention efforts. Five routinely collected administrative data
      collections in NSW in the period 2000-2012 were reviewed. The WHO core minimum
      data items recorded in each of the five data collections ranged from 37.5% to
      75.0%. Age and sex of the injured individual were the only data items that were
      recorded in all data collections. The data collections did not contain detailed
      information on the circumstances of quad bike incidents. Major improvements are
      needed in the information collected in these data-sets, if their value is to be
      increased and used for injury prevention purposes. 

PMID- 25564293
TI  - Analysis of signaling networks distributed over intracellular compartments based
      on protein-protein interactions.
AB  - BACKGROUND: Biological processes are usually distributed over various
      intracellular compartments. Proteins from diverse cellular compartments are often
      involved in similar signaling networks. However, the difference in the reaction
      rates between similar proteins among different compartments is usually quite
      high. We suggest that the estimation of frequency of intracompartmental as well
      as intercompartmental protein-protein interactions is an appropriate approach to
      predict the efficiency of a pathway. RESULTS: Using data from the databases
      STRING, ANDSystem, IntAct and UniProt, a PPI frequency matrix of intra/inter
      compartmental interactions efficiencies was constructed. This matrix included 15
      human-specific cellular compartments. An approach for estimating pathway
      efficiency using the matrix of intra/inter-compartmental PPI frequency, based on
      analysis of reactions efficiencies distribution was suggested. An investigation
      of KEGG pathway efficiencies was conducted using the developed method. The
      clusterization and the ranking of KEGG pathways based on their efficiency were
      performed. "Amino acid metabolism" and "Genetic information processing" revealed
      the highest efficiencies among other functional classes of KEGG pathways.
      "Nervous system" and "Signaling molecules interaction" contained the most
      inefficient pathways. Statistically significant differences were found between
      efficiencies of KEGG and randomly-generated pathways. Based on these
      observations, the validity of this approach was discussed. CONCLUSION: The
      estimation of efficiency of signaling networks is a complicated task because of
      the need for the data on the kinetic reactions. However, the proposed method does
      not require such data and can be used for preliminary analysis of different
      protein networks.

PMID- 25564294
TI  - Evaluation of the antioxidant and antibacterial properties of ethanol extracts
      from berries, leaves and stems of Hedera pastuchovii Woron. ex Grossh.
AB  - This study was designed to examine the total phenolic and flavonoid contents,
      radical scavenging and antibacterial activity of the ethanolic extracts from
      leaves, berries and stems of Hedera pastuchovii Woron. ex Grossh. The berry
      extract, which contained the highest phenolic and flavonoid compounds, showed an
      appreciable DPPH(.) scavenging ability in comparison with leaf and stem extracts.
      The various extracts exhibited moderate to good activity against both Gram
      negative and Gram-positive bacteria, and the effectiveness of leaf extract was
      higher for all tested bacteria.

PMID- 25564295
TI  - Impaired migration capacity in monocytes derived from patients with Gaucher
      disease.
AB  - Gaucher disease (GD) is characterized by glucocerebroside (GC) accumulation due
      to defective activity of the glucocerebrosidase (GlcCerase) enzyme. Monocytes and
      macrophages exhibit the highest GlcCerase activity and are most prominently
      affected by GC engorgement. As GD patients tend to exert various immune system
      related changes, this study was designed to investigate potential effects of
      monocyte dysfunction on these alterations. Monocytes were isolated from
      peripheral blood mononuclear cells (PBMCs) of untreated GD patients and healthy
      volunteers. Monocyte migration capacity towards SDF1alpha was assessed. The GD
      patients exhibited reduced numbers of monocytes and decreased capability of
      SDF1alpha-dependent monocyte migration. Evaluation of CXCR4, the SDF1alpha
      receptor, revealed reduced expression of surface CXCR4 on GD-derived monocytes,
      despite similar CXCR4 mRNA transcript levels in the monocytes of healthy
      volunteers and GD patients. Reduction of surface CXCR4 was accompanied by
      increased intracellular CXCR4 levels in patient monocytes. This elevated
      intracellular CXCR4 might reflect significantly increased SDF1alpha
      concentrations characterizing patients' serum and the lysosomal impairment of GD,
      resulting in decreased degradation of CXCR4. Different distributions of CXCR4
      expression observed in the two groups explain impaired SDF1alpha-dependent
      monocyte migration. Reduced numbers and impaired migration capacity of GD-derived
      monocytes could contribute to abnormal inflammation and GD-associated immune
      alterations seen in these patients. 

PMID- 25564296
TI  - Investigation of the non-Gaussian water diffusion properties in bladder cancer
      using diffusion kurtosis imaging: a preliminary study.
AB  - OBJECTIVE: The objective of this study was to investigate the non-Gaussian water
      diffusion properties in bladder cancer and assess the efficacy of diffusion
      kurtosis imaging for estimating the histological grade of bladder cancer.
      METHODS: Twenty-one patients with bladder cancer (high-grade, 12; low-grade, 9)
      and 17 negative controls who underwent preoperative 3.0-T magnetic resonance
      imaging including multi-b value diffusion-weighted imaging (b values, 0, 500,
      800, 1200, 1500, and 2000 s/mm) were included. Besides apparent diffusion
      coefficient (ADC) maps, diffusion kurtosis imaging maps for diffusion coefficient
      (Dapp) and kurtosis (Kapp) were also obtained. Data were analyzed using the Mann
      Whitney U test, Spearman correlation test, and receiver operating characteristic
      curves. RESULTS: Bladder cancer showed significantly lower ADC values, lower Dapp
      values, and higher Kapp values compared with normal bladder wall (all P < 0.001).
      The Kapp values were significantly higher in high-grade than in low-grade tumors
      (P = 0.007). Significant correlations were found between Dapp and ADC (r = 0.901,
      P < 0001) as well as between Kapp and ADC (r = -0.910, P <0.001). The areas under
      the receiver operating characteristic curve were 0.843 and 0.796 for estimation
      of high-grade bladder cancer by using the Kapp values and ADC values,
      respectively. CONCLUSIONS: Diffusion in bladder cancer follows a non-Gaussian
      behavior. The new metric Kapp may potentially serve as a biomarker of grade of
      bladder cancer.

PMID- 25564297
TI  - Assessment of single-bolus contrast administration technique using hybrid dual
      source ECG-gated thoracic and dual-source non-ECG-gated high-pitch abdominopelvic
      CT acquisitions for procedural planning before transcatheter aortic valve
      replacement.
AB  - PURPOSE: This study aimed to assess vascular contrast opacification and
      homogeneity using single-bolus contrast administration with hybrid thoracic and
      abdominopelvic computed tomographic angiography in patients with severe aortic
      valve stenosis. MATERIALS AND METHODS: Combination electrocardiogram-gated
      thoracic and dual-source, high-pitch abdominopelvic computed tomographic
      angiography examinations of 50 patients with severe aortic stenosis between
      December 2013 and March 2014 were reviewed. Contrast administration was
      individualized to patient-specific physiology. Image analysis of vascular
      opacification was obtained and interdependencies of vascular contrast and
      homogeneity of contrast distribution were assessed. RESULTS: The mean volume of
      contrast administered was 106 +/- 11.7 mL. Mean attenuation was 371 +/- 90.7
      Hounsfield units (HU) in the thoracic aorta and 388 +/- 95.9 HU in the abdominal
      aorta. Homogeneous opacification was obtained throughout with coefficient of
      variation of 11%. CONCLUSIONS: Procedural planning for transcatheter aortic valve
      replacement can be achieved using a single-injection bolus contrast protocol in
      combination with a 2-part multidetector computed tomographic image acquisition
      technique with optimal opacification of major arterial structures.

PMID- 25564298
TI  - CTCA image quality improvement by using snapshot freeze technique under
      prospective and retrospective electrocardiographic gating.
AB  - BACKGROUND: Although coronary computed tomography angiography (CCTA) can detect
      coronary artery disease, limited temporal resolution of computed tomographic
      scanners may allow for motion artifacts, which may result in nonevaluable
      coronary segments. OBJECTIVE: This study aimed to assess Snapshot Freeze (SSF)
      Motion Correction algorithm for its effect on image quality of CCTA. METHODS AND
      RESULTS: Thirty patients underwent prospective electrocardiographic (ECG)-gating
      CCTA and 30 patients underwent retrospective ECG gating. In prospective ECG
      gating group, SSF showed higher interpretability than standard (STD) on per
      artery [97.8% (88/90) vs 87.8% (79/90), P = 0.004] and per-segment level [99.1%
      (427/431) vs 96.1% (414/431), P = 0.000]. Image quality was higher with SSF than
      STD on per-patient [3.5 (0.9) vs 2.9 (1.2), P = 0.004], per-artery [3.5 (0.8) vs
      3.1 (1.0), P = 0.000], and per-segment levels [3.7 (0.8) vs 3.4 (1.0), P =
      0.000]. In retrospective ECG-gating group, SSF showed higher interpretability
      than STD on per-patient [80.0% (24/30) vs 53.3% (16/30), P = 0.039], per-artery
      [90.0% (81/90) vs 71.1% (64/90), P = 0.000], and per-segment levels [98.1%
      (413/421) vs 90.7% (382/421), P = 0.000] of 45% R-R interval images. Snapshot
      freeze showed higher interpretability than STD on per-artery [70.0% (63/90) vs
      55.6% (50/90), P = 0.02] and per-segment levels [82.7% (348/421) vs 78.4%
      (330/421), P = 0.018]. Image quality was higher with SSF than STD on per-patient
      [2.8 (1.0) vs 2.1 (1.2), P = 0.013] [2.1 (1.2) vs 1.6 (1.0), P = 0.026], per
      artery [3.0 (0.9) vs 2.4 (1.0), P = 0.000] [2.6 (1.2) vs 2.2 (1.2), P = 0.000],
      and per-segment levels [3.3 (0.9) vs 2.9 (1.0), P = 0.000] [2.9 (1.2) vs 2.7
      (1.1), P = 0.000] of 45% and 75% R-R interval images. CONCLUSIONS: Snapshot
      freeze could improve the image quality and interpretability of CCTA with
      prospective and retrospective ECG gating. Especially, SSF could improve the image
      quality on right coronary artery by using the 45% R-R interval as the central
      phase with retrospective ECG gating.

PMID- 25564299
TI  - Computed tomography appearance of normal nonossified thyroid cartilage:
      implication for tumor invasion diagnosis.
AB  - OBJECTIVE: The objective of this study was to determine the density and
      homogeneity of the nonossified thyroid cartilage (NOTC) on contrast-enhanced
      computed tomography (CT) providing preliminary information for future evaluation
      of cartilage invasion using dual-energy CT. METHODS: One hundred normal-larynx CT
      scans were evaluated for the density and homogeneity of NOTC. RESULTS: The
      density of the NOTC was homogeneous in all cases. Nonossified thyroid cartilage
      had higher mean density than contiguous muscle, but there was overlap. In 47
      cases, a lucent area was observed at the junction of the ossified and NOTC but
      not within the NOTC itself. In 11 cases, ossification was observed in only 1
      cortex of the thyroid cartilage. Cartilage at the anterior commissure was not
      ossified in 7 cases. CONCLUSIONS: Nonossified thyroid cartilage has a homogeneous
      appearance on contrast-enhanced CT scans, but showed some normal variations that
      could be mistakenly reported as tumor invasion.

PMID- 25564300
TI  - Diffusion tensor imaging of the anterior cruciate ligament graft after
      reconstruction: repeatability and diffusion tensor imaging metrics.
AB  - PURPOSE: The purpose of the study was to explore the feasibility and
      repeatability of diffusion tensor imaging and diffusion tractography on the
      anterior cruciate ligament graft after reconstruction and determine the
      fractional anisotropy and mean apparent diffusion coefficient values. MATERIALS
      AND METHODS: Twenty-two patients who underwent anterior cruciate ligament
      reconstruction operation were scanned at 3-T clinical magnetic resonance scanner.
      The fiber tracking and other postprocessing steps were carried out twice by a
      radiologist on the workstation and repeated by another radiologist. Diffusion
      tensor metrics of different parts of the grafts were determined with region of
      interest- and fiber tractography-based measurements, and the intraobserver and
      interobserver measurement variances were calculated. RESULTS: Tractography
      illustrated nicely the 3-dimensional courses of the graft in all 22 cases. The
      mean fractional anisotropy value of the intratunnel part was significantly higher
      than that of the intra-articular part, whereas the mean apparent diffusion
      coefficient value of the intratunnel part was lower when compared with that of
      the intra-articular part. According to the 2-sided paired samples Student t test,
      the intraobserver and interobserver measurements correlated well. CONCLUSIONS:
      Diffusion tensor imaging and diffusion tractography can be used to visualize the
      anterior cruciate ligament grafts and can provide additional information over
      standard morphologic magnetic resonance imaging.

PMID- 25564301
TI  - Rhabdoid tumor: an aggressive renal medullary tumor of childhood.
AB  - We present a case of a renal rhabdoid tumor in a 2-month-old girl. Rhabdoid
      tumors are rare primary renal tumors in children, but they have characteristic
      features--medullary sinus invasion and subcapsular fluid collections--which
      enable a specific diagnosis. The classic imaging characteristics of this tumor
      compared to other more common primary pediatric renal tumors will be reviewed.

PMID- 25564302
TI  - Integration of dose counters in pressurized metered-dose inhalers for patients
      with asthma and chronic obstructive pulmonary disease: review of evidence.
AB  - INTRODUCTION: An important factor responsible for suboptimal treatment in
      patients with obstructive airway diseases, which is often overlooked, is running
      out of medication. Addition of a dose counter to a pressurized metered-dose
      inhaler (pMDI) allows the patient to reliably track number of actuations,
      identify when the label claim number of actuations has been reached, and when a
      new inhaler needs to be purchased. AREAS COVERED: This article discusses the
      conventional methods for tracking doses in pMDIs, rationale of using dose
      counters, published evidence of studies, including performance and patient
      satisfaction with the use of pMDIs with dose counter. A section on the FDA
      guidance on dose counters and on Cipla's dose counters is also included. EXPERT
      OPINION: It has been several years since the US FDA guidance on integration of
      dose-counting mechanisms into pMDIs and some time since pMDIs with dose counters
      have been available (albeit not with all pMDIs); but their importance has not
      been fully realized. This can be due to factors such as lack of adequate
      understanding about dose tracking, limited pMDIs being available with integrated
      dose counters and absence of a clear consolidation of the need, advantages,
      guidelines, types and characteristics of dose counters in published articles.

PMID- 25564303
TI  - Review: An overview of molecular events occurring in human trophoblast fusion.
AB  - During human placentation, mononuclear cytotrophoblasts fuse to form a
      multinucleated syncytia ensuring hormonal production and nutrient exchanges
      between the maternal and fetal circulation. Syncytia formation is essential for
      the maintenance of pregnancy and for fetal growth. The trophoblast cell fusion
      process first requires the acquisition of cell fusion properties, then cells set
      up plasma membrane protein macrocomplexes and fusogen machinery that trigger cell
      cell fusion. Numerous proteins have been shown to be directly involved in the
      initiation of trophoblast cell fusion. These proteins must expressed at the right
      time and in the right place to trigger cell-cell fusion. In this review, we
      describe the role of certain fusogenic protein macrocomplexes that form the
      scaffold for the fusogen machinery underlying human trophoblastic-lipid mixing
      and merging of cell contents that lead to cell fusion in physiological
      conditions. 

PMID- 25564304
TI  - Combining silver- and organocatalysis: an enantioselective sequential catalytic
      approach towards pyrano-annulated pyrazoles.
AB  - A one-pot asymmetric Michael addition/hydroalkoxylation sequence, catalyzed by a
      sequential catalytic system consisting of a squaramide and a silver salt,
      provides a new series of chiral pyrano-annulated pyrazole derivatives in
      excellent yields (up to 95%) and high enantioselectivities (up to 97% ee). 

PMID- 25564305
TI  - Shared structural features of the 9aaTAD family in complex with CBP.
AB  - A number of transactivation domains for transcription factors including p53,
      E2A/HEB, MLL, cMyb, CREB, FOXO3, Gcn4, Oaf1 and Pdr1 have been reported to
      interact with the KIX domain of general transcriptional mediators CBP, p300 or
      MED15. Most of those factors belong to the already established Nine amino acid
      Transactivation Domain (9aaTAD) family. By using available structural data, we
      found binding analogy for the 9aaTAD in the MLL-KIX and also E2A/HEB-KIX
      complexes. We recognized two distinct TAD formations in the KIX complex. In the
      E2A/HEB-KIX complex, the leucine position is determined by the prolonged helical
      structure including the 9aaTAD and the leucine (long-helical TAD). However in the
      MLL-KIX complex, the equal position of 9aaTAD and proximal leucine is achieved
      differently by leucine-turn-helix structural architecture. Furthermore, the FOXO3
      KIX complex shares structural analogy with the E2A-KIX complex in respect of both
      9aaTAD and proximal leucine. Next, from (i) sequence alignment of the identified
      9aaTADs in p53, E2A/HEB and MLL proteins and (ii) the resolved structure of the
      MLL-KIX and E2A/HEB-KIX complexes, we generated a plausible structural model for
      p53 that could be used also for other members of the 9aaTAD family. The position
      of 9aaTADs in Oaf1-, Pdr1- and Gcn4-MED15 KIX complexes and 9aaTAD composition
      are in good agreement with E2A, MLL, FOXO3 and p53. Analyses of structural data
      in this study define fundamental structural requirements and shed more light on
      the ambiguous 9aaTAD domain. 

PMID- 25564307
TI  - A QM/MM free energy study of the oxidation mechanism of dihydroorotate
      dehydrogenase (class 1A) from Lactococcus lactis.
AB  - The dihydroorotate dehydrogenase (DHOD) class 1A enzyme catalyzes is the only
      redox enzyme in the biosynthetic pathway (de novo) of pyrimidines where
      dihydroorotate (DHO) is oxidized to orotate (OA) coupled to reduction of a flavin
      mononucleotide (FMN) cofactor. The rupture of two DHO C-H bonds can proceed in a
      concerted or stepwise way. Herein, the catalytic mechanism of DHOD from
      Lactococcus lactis involving DHO oxidation (first half-reaction) was described
      using a hybrid quantum mechanics/molecular mechanics (QM/MM) approach and
      molecular dynamics simulations. The free energy profile obtained from self
      consistent charge-density functional tight binding/molecular mechanics
      calculations (corrected by DFT/MM) reveals that this occurs with the proton
      abstraction from DHO C5 to Cys130 deprotonated and DHO H6 is transferred to FMN
      N5 in a concerted mechanism with a very low barrier of 5.64 kcal/mol. Finally,
      through a residual decomposition analysis, the residues that have the main
      influence on the redox reaction were identified. 

PMID- 25564308
TI  - The efficacy and safety of rituximab in a chart review study of 15 patients with
      systemic lupus erythematosus.
AB  - In contrast to randomised clinical trials, open-label studies have suggested that
      B cell depletion by a course of rituximab is associated with a significant
      clinical benefit. Our aim was to assess the safety and efficacy of rituximab in
      15 refractory lupus patients, particularly those with more than one course of
      therapy. Disease activity was measured by the classic British Isles Lupus
      Assessment Group (BILAG) index, anti-DNA antibodies and complement levels. We
      assessed immunoglobulin levels, functional antibodies and serious adverse events.
      The mean patient age +/- SD was 37.9 +/- 7.2 years and mean disease duration was
      8.5 +/- 3.3 years; 46% were Afro-Caribbean, 27% South Asian, 20% Caucasian and 7%
      others. Twelve patients responded by 6 months; six avoided major flare for >1
      year. Complete absence of disease activity (BILAG D/E) lasted for 5.5 (SD 3.8)
      months and 4.8 (SD 3.6) months after the first (n = 15) and second (n = 9)
      rituximab course, respectively. The mean 6-month reduction in daily prednisolone
      was 10.4 (SD 11.4) mg/day and 10.7 (SD 9.3) mg/day from baseline after the first
      and second course, respectively. Patients with low C3/C4 normalised their C3 by 6
      months. Most patients with raised anti-dsDNA normalised after rituximab courses.
      Serious adverse events only occurred after more than four courses of rituximab.
      Rituximab was safe and efficacious for treating patients with refractory systemic
      lupus erythematosus (SLE) and was associated with significant steroid reduction,
      but more than four courses of rituximab was associated with an increased risk of
      serious infection in two patients.

PMID- 25564306
TI  - An unusual peroxo intermediate of the arylamine oxygenase of the chloramphenicol
      biosynthetic pathway.
AB  - Streptomyces venezuelae CmlI catalyzes the six-electron oxygenation of the
      arylamine precursor of chloramphenicol in a nonribosomal peptide synthetase
      (NRPS)-based pathway to yield the nitroaryl group of the antibiotic. Optical,
      EPR, and Mossbauer studies show that the enzyme contains a nonheme dinuclear iron
      cluster. Addition of O(2) to the diferrous state of the cluster results in an
      exceptionally long-lived intermediate (t(1/2) = 3 h at 4  degrees C) that is
      assigned as a peroxodiferric species (CmlI-peroxo) based upon the observation of
      an (18)O(2)-sensitive resonance Raman (rR) vibration. CmlI-peroxo is
      spectroscopically distinct from the well characterized and commonly observed cis
      MU-1,2-peroxo (MU-eta(1):eta(1)) intermediates of nonheme diiron enzymes.
      Specifically, it exhibits a blue-shifted broad absorption band around 500 nm and
      a rR spectrum with a nu(O-O) that is at least 60 cm(-1) lower in energy.
      Mossbauer studies of the peroxo state reveal a diferric cluster having iron sites
      with small quadrupole splittings and distinct isomer shifts (0.54 and 0.62 mm/s).
      Taken together, the spectroscopic comparisons clearly indicate that CmlI-peroxo
      does not have a MU-eta(1):eta(1)-peroxo ligand; we propose that a MU
      eta(1):eta(2)-peroxo ligand accounts for its distinct spectroscopic properties.
      CmlI-peroxo reacts with a range of arylamine substrates by an apparent second
      order process, indicating that CmlI-peroxo is the reactive species of the
      catalytic cycle. Efficient production of chloramphenicol from the free arylamine
      precursor suggests that CmlI catalyzes the ultimate step in the biosynthetic
      pathway and that the precursor is not bound to the NRPS during this step.

PMID- 25564309
TI  - The expression of death decoy receptor 3 was increased in the patients with
      primary Sjogren's syndrome.
AB  - Previous studies suggested a pathological role for the death decoy receptor 3
      (DcR3) in systemic lupus erythematosus (SLE) and rheumatic arthritis (RA).
      Herein, the expression of DcR3 in primary Sjogren's syndrome (pSS) and the
      relationship with clinical characteristics were investigated. The serum DcR3
      levels of pSS patients and healthy controls were measured by ELISA. Pearson's
      correlation analysis was used to evaluate the relationship between the DcR3
      levels with the clinical characterstics of pSS patients. Additionally, the DcR3
      expression in salivary glands of pSS patients was investigated by the
      immunohistochemistry method. The serum DcR3 expression in pSS patients was
      significantly higher than healthy controls (p < 0.001), especially in new onset
      pSS patients (p = 0.036). Moreover, Pearson's correlation analysis show that DcR3
      levels were positively correlated with age (p = 0.013), platelet (PLT) (p =
      0.002), hemoglobin (Hb) (p = 0.004), Sjogren's syndrome disease damage activity
      index (SSDAI) score (p = 0.005), Sjogren's syndrome disease damage index (SSDDI)
      score (p < 0.001) and EULAR Sjogren's syndrome disease activity index (ESSDAI)
      score (p = 0.010). Furthermore, the DcR3 levels were significantly lower when the
      pSS patients were treated with the disease-modifying anti-rheumatic drugs. At
      last, DcR3 expression in salivary glands of pSS patients was significantly higher
      than healthy controls. The DcR3 expression was significantly elevated in the pSS
      patients and positively correlated with the clinical characteristics, and it
      might be an important factor involved in the progression of pSS patients and
      could be a potential therapeutic target.

PMID- 25564310
TI  - Detection of mouse endogenous type B astrocytes migrating towards brain lesions.
AB  - Neuroblasts represent the predominant migrating cell type in the adult mouse
      brain. There are, however, increasing evidences of migration of other neural
      precursors. This work aims at identifying in vivo endogenous early neural
      precursors, different from neuroblasts, able to migrate in response to brain
      injuries. The monoclonal antibody Nilo1, which unequivocally identifies type B
      astrocytes and embryonic radial glia, was coupled to magnetic glyconanoparticles
      (mGNPs). Here we show that Nilo1-mGNPs in combination with magnetic resonance
      imaging in living mice allowed the in vivo identification of endogenous type B
      astrocytes at their niche, as well as their migration to the lesion site in
      response to glioblastoma, demyelination, cryolesion or mechanical injuries. In
      addition, Nilo1(+) adult radial glia-like structures were identified at the
      lesion site a few hours after damage. For all damage models used, type B
      astrocyte migration was fast and orderly. Identification of Nilo1(+) cells
      surrounding an induced glioblastoma was also possible after intraperitoneal
      injection of the antibody. This opens up the possibility of an early
      identification of the initial damage site(s) after brain insults, by the
      migration of type B astrocytes. 

PMID- 25564311
TI  - Detection of epileptic seizures with a modified heart rate variability algorithm
      based on Lorenz plot.
AB  - PURPOSE: In order to assess whether focal epileptic seizures can be detected and
      distinguished from exercise we evaluated four different heart rate variability
      (HRV) methods with short term moving window analysis of 30, 50 or 100 R-R
      intervals or seconds per analyzed window. METHODS: The four methods consisted of:
      (1) reciprocal high frequency power based on Fast Fourier Transformation, (2)
      Cardiac Sympathetic Index (CSI), (3) Modified CSI both based on Lorenz plot, and
      (4) heart rate differential method. Seventeen patients (12 males, 5 females; age
      20-55) had 47 seizures (including three secondary generalized tonic-clonic
      (sGTC)), which were analyzed during their long term video-EEG monitoring of 1-5
      days duration. Positive seizure detection was regarded, when the HRV-value during
      seizures (1min before to 3min after seizure-onset) exceeded 105% of the highest
      value during exercise and non-seizure sample-periods of the same patient.
      RESULTS: Modified CSI100 was the most accurate method: it detected all seizures
      for 13 of the 17 patients within 6s before till 50s after seizure onset time,
      even though exercise maximum HR of each patient exceeded that of the seizures.
      The three sGTC seizures were all detected more than half a minute before the
      tonic-clonic phase. CONCLUSION: The results indicate a detectable, sudden and
      inordinate shift toward sympathetic overdrive in the sympathovagal balance of the
      autonomic nervous system around seizure-onset time, for most patients. The
      Modified CSI is a promising parameter for a portable ECG-based epilepsy alarm,
      detecting both focal and sGTC seizures.

PMID- 25564313
TI  - Blinking and eyelid myoclonia: Characteristics and correlations of eyelid
      movements.
AB  - PURPOSE: Eyelid myoclonia (EM) is considered a seizure type and has been
      described in several epileptic conditions. Previous studies reported that EM are
      precipitated only by slow eye closure, but little is known about the
      characteristics of blinking in patients with EM seizures and differences in
      precipitation of EM by different kinds of eye closure. We analyzed by video-EEG
      the characteristics of blinking and eye closure in these patients. METHOD: Twenty
      patients with EM had a video-EEG protocol with eyelid sensors. Semiology and rate
      of blinking and EM were analyzed. Statistical analysis was performed and p-values
      <0.05 were considered significant. RESULTS: Seventeen cases (mean age 20.7, range
      3-35) were women, 10 had EM as the main seizure type and between the others, all,
      but one, had criteria to Juvenile Myoclonic Epilepsy. All patients presented EM,
      18 spontaneously during awake, 10 on eye closure and one only during intermittent
      photic stimulation. EM assumed the form of flicker, flutter or jerk, accompanied
      by generalized discharges, spiky posterior alpha, theta rhythm or absence of any
      EEG abnormality. Analysis of the characteristics of blinking had no statistics
      differences between patients and healthy subjects. The rate of blinks and EM
      increased during speech and decreased during reading. EM never occurred during
      blinking or in the dark. CONCLUSIONS: Despite normal physiology of blinking, EM
      can manifest as jerk, flicker or flutter, with or without EEG abnormalities and
      independently of IPS, suggesting that eye closure sensitivity seems to include
      both, a motor and a visual component.

PMID- 25564312
TI  - Do pure absence seizures occur in myoclonic epilepsy of infancy? A case series.
AB  - PURPOSE: To assess if absence seizures (ASs) occur in patients with myoclonic
      epilepsy of infancy (MEI). METHODS: A retrospective chart review was conducted in
      37 patients with MEI followed at seven different paediatric epilepsy centres in
      Italy, between 2002 and 2014. To assess the possible occurrence of pure ASs or
      absences associated with myoclonias, ASs were defined according to the following
      criteria: (i) a sudden onset and interruption of ongoing activities; (ii)
      bilateral polyspikes or spike-and-wave (SW) complexes; spike SW complexes at 2
      4Hz; (iii) duration of AS: 3-30seconds. RESULTS: Thirty-seven MEI patients (25
      boys and 12 girls) were identified. Nine patients (24.3%) had a history of simple
      FS during the first year of life. Ten patients (27%) had a family history of
      epilepsy, and six patients (16.2%) had a family history of FS. In 7/37 (18.9%)
      patients, during the occurrence of MSs, a total of nineteen brief ASs were
      captured by video-EEG recordings. ASs occurred both during a brief cluster of
      rhythmic MSs than after single myoclonic jerks. The ictal EEG abnormalities
      observed in patients with ASs were similar to the ictal EEG patterns associated
      with only myoclonias. No differences in relation to gender, family history, ictal
      EEG discharge were found between patients with myoclonic seizures with ASs and
      myoclonias without ASs. CONCLUSIONS: Absence seizures can occur in approximately
      20% of MEI patients and the occurrence of ASs, though not essential to formulate
      the diagnosis, do not automatically exclude the diagnosis of MEI.

PMID- 25564314
TI  - Cost of status epilepticus: A systematic review.
AB  - The objective of this review is to give an overview of published cost of illness
      (COI) studies on status epilepticus (SE). For identifying COI studies that
      evaluated the direct and indirect costs of SE, a systematic literature review was
      performed. We used a standardized assessment form for extracting information on
      the study design, methodological framework, and data sources from each
      publication. The results were systematically reported. We identified only two
      studies worldwide, which included prevalence- or incidence-based data on the
      direct costs of SE: one from Germany and one from the USA. Both used a bottom-up
      approach and a prospective design. The estimated mean inpatient costs summed up
      to US$18,834 in the USA and to ?8347 in Germany per admission with an average
      length of stay of 12.9 and 14.0 days. The mean annual direct costs for SE had
      been estimated at US$4 billion in the USA and at ?83 million (adults only) in
      Germany. Both available studies indicate that SE is a cost-intensive disorder
      with an acute CNS aetiology as a cost-driving factor. In conclusion, there is a
      paucity of data on the costs of SE. Further studies are warranted to determine
      costs, its predictors, quality of life, mortality data due to SE and its sequelae
      and to provide a basis for further cost-effectiveness calculations for new drugs
      and other interventions in SE and prolonged seizures. 

PMID- 25564315
TI  - Can pentylenetetrazole and maximal electroshock rodent seizure models
      quantitatively predict antiepileptic efficacy in humans?
AB  - PURPOSE: Pentylenetetrazole and maximal electroshock rodent seizure models are
      commonly used to detect antiepileptic efficacy in drug development. The aim of
      this research was to evaluate the predictive capabilities of pentylenetetrazole
      and maximal electroshock models in estimating human exposures required for
      antiepileptic efficacy through a survey of current literature. METHODS: A
      literature search was undertaken to identify articles describing
      pentylenetetrazole or maximal electroshock models in rat or mice, where at least
      one of nine pre-selected antiepileptic drugs based on evidence of efficacy were
      used. Exposures at the median doses of the approved human dose range for these
      drugs were compared to exposures at doses that inhibit maximal response by 50%
      (ED50s) from the pentylenetetrazole and maximal electroshock models. Ratios of
      the human to rodent exposures were calculated and summarised statistically and
      graphically. RESULTS: Across the nine antiepileptic drugs investigated, the
      average (standard deviation) ratio of exposures comparing the median human
      efficacious dose to mice ED50 dose was 1.4 (3.9) for the pentylenetetrazole model
      and 3.8 (3.1) for the maximal electroshock model. In the rat, ratios in the
      maximal electroshock and pentylenetetrazole model were 4.1 (2.1) and a range of 1
      2, respectively. CONCLUSION: Based on the nine antiepileptic drugs investigated,
      the pentylenetetrazole model appeared to predict human exposures more accurately
      than the maximal electroshock model. There did not appear to be differences
      between rat and mice in either of the seizure models, therefore both species
      could be used equally. Both the pentylenetetrazole and maximal electroshock
      models are useful tools in screening compounds in early drug discovery.

PMID- 25564317
TI  - The management of Convulsive Refractory Status Epilepticus in adults in the UK:
      No consistency in practice and little access to continuous EEG monitoring.
AB  - PURPOSE: Convulsive Status Epilepticus (CSE) is a common neurological emergency
      with patients presenting with prolonged epileptic activity. Sub-optimal
      management is coupled with high morbidity and mortality. Continuous
      electroencephalogram (EEG) monitoring is considered essential by the National
      Institute for Health and Care Excellence (NICE) in the management of Convulsive
      Refractory Status Epilepticus (CRSE). The aim of this research was to determine
      current clinical practice in the management of CRSE amongst adults in intensive
      care units (ICU) in the UK and establish if the use of a standardised protocol
      requires re-enforcement within trusts. METHODS: 75 randomly selected UK NHS
      Trusts were contacted and asked to complete a questionnaire in addition to
      providing their protocol for CRSE management in ICU. RESULTS: 55 (73%) trusts
      responded. While 31 (56% of responders) had a protocol available in ICU for early
      stages of CSE, just 21 (38%) trusts had specific guidelines if CRSE occurred.
      Only 23 (42%) trusts involved neurologists at any stage of management and just 18
      (33%) have access to continuous EEG monitoring. CONCLUSION: This study identifies
      significant inconsistency in the management of CSE in ICU's across the UK. A
      minority of ICU units have a protocol for CRSE or access to continuous EEG
      monitoring despite it being considered fundamental for management and supported
      by NICE guidance.

PMID- 25564316
TI  - Sporadic and familial glut1ds Italian patients: A wide clinical variability.
AB  - PURPOSE: GLUT1 deficiency syndrome is a treatable neurological disorder
      characterized by developmental delay, movement disorders and epilepsy. It is
      caused by mutations in the SLC2A1 gene inherited as an autosomal dominant trait
      with complete penetrance, even if most detected SCL2A1 mutations are de novo. Our
      aim is to present a wide series of Italian patients to highlight the differences
      among subjects with de novo mutations and those with familial transmission.
      METHODS: We present clinical and genetic features in a series of 22 GLUT1DS
      Italian patients. Our patients were classified in two different groups: familial
      cases including GLUT1DS patients with genetically confirmed affected relatives
      and sporadic cases with detection of SLC2A1 de novo mutation. RESULTS: We found
      remarkable differences in the severity of the clinical picture regarding the type
      of genetic inheritance (sporadic versus familial): sporadic patients were
      characterized by an earlier epilepsy-onset and higher degree of intellectual
      disability. No significant differences were found in terms of type of movement
      disorder, whilst Paroxysmal Exertion-induced Dyskinesia (PED) is confirmed to be
      the most characteristic movement disorder type in GLUT1DS. In familial cases the
      clinical manifestation of the disease was particularly variable and
      heterogeneous, also including asymptomatic patients or those with minimal
      symptoms. CONCLUSION: The finding of a "mild" phenotype in familial GLUT1DS gives
      rise to several questions: the real incidence of the disease, treatment option
      with ketogenic diet in adult patients and genetic counseling.

PMID- 25564318
TI  - Perceived stigma in Korean adolescents with epilepsy: Effects of knowledge about
      epilepsy and maternal perception of stigma.
AB  - PURPOSE: There has been little research on whether the knowledge that adolescents
      with epilepsy (AWE) or their family have about the condition reduces their
      perception of stigma. In this study we determine the relation between AWE's
      perceived stigma of, and knowledge about, epilepsy and maternal perception of
      stigma. METHODS: This was a cross-sectional multicenter study involving AWE and
      their mothers from 25 secondary or tertiary hospitals in Korea. The level of
      knowledge about epilepsy was assessed using 34 medical items of the Epilepsy
      Knowledge Profile-General (EKP-M). Additional questionnaires included the Child
      Stigma Scale, Parent Stigma Scale, and the Maternal Disclosure Management Scale.
      RESULTS: A total of 243 AWE and their mothers were included. The mean EKP-M score
      was 20.7 (range, 12-31) for AWE and 22.0 (range, 11-31) for their mothers. AWE
      and mothers had a neutral perception of stigma on average, but the maternal
      concealment behavior was high. Multiple linear regression indicated that AWE's
      knowledge about epilepsy was significantly related to their perception of stigma.
      Unexpectedly, AWE with a low level of knowledge reported a higher perception of
      stigma than those with a very low level of knowledge (beta=0.280, p=0.040). In
      addition, higher maternal concealment behavior (beta=0.070, p=0.002) and
      receiving polytherapy (beta=0.240, p=0.046) were independent factors predicting
      higher perception of stigma in AWE. CONCLUSION: The knowledge that the AWE had
      about their epilepsy, maternal concealment behavior, and receiving polytherapy
      were significantly related to the AWE's perception of stigma.

PMID- 25564320
TI  - Publishing considerations for new academic nursing faculty.

PMID- 25564319
TI  - Forced unraveling of chromatin fibers with nonuniform linker DNA lengths.
AB  - The chromatin fiber undergoes significant structural changes during the cell's
      life cycle to modulate DNA accessibility. Detailed mechanisms of such structural
      transformations of chromatin fibers as affected by various internal and external
      conditions such as the ionic conditions of the medium, the linker DNA length, and
      the presence of linker histones, constitute an open challenge. Here we utilize
      Monte Carlo (MC) simulations of a coarse grained model of chromatin with
      nonuniform linker DNA lengths as found in vivo to help explain some aspects of
      this challenge. We investigate the unfolding mechanisms of chromatin fibers with
      alternating linker lengths of 26-62 bp and 44-79 bp using a series of end-to-end
      stretching trajectories with and without linker histones and compare results to
      uniform-linker-length fibers. We find that linker histones increase overall
      resistance of nonuniform fibers and lead to fiber unfolding with superbeads-on-a
      string cluster transitions. Chromatin fibers with nonuniform linker DNA lengths
      display a more complex, multi-step yet smoother process of unfolding compared to
      their uniform counterparts, likely due to the existence of a more continuous
      range of nucleosome-nucleosome interactions. This finding echoes the theme that
      some heterogeneity in fiber component is biologically advantageous. 

PMID- 25564321
TI  - Kinetic and thermodynamic analyses of spontaneous exchange between high-density
      lipoprotein-bound and lipid-free apolipoprotein A-I.
AB  - It is thought that apolipoprotein A-I (apoA-I) spontaneously exchanges between
      high-density lipoprotein (HDL)-bound and lipid-free states, which is relevant to
      the occurrence of prebeta-HDL particles in plasma. To improve our understanding
      of the mechanistic basis for this phenomenon, we performed kinetic and
      thermodynamic analyses for apoA-I exchange between discoidal HDL-bound and lipid
      free forms using fluorescence-labeled apoA-I variants. Gel filtration experiments
      demonstrated that addition of excess lipid-free apoA-I to discoidal HDL particles
      promotes exchange of apoA-I between HDL-associated and lipid-free pools without
      alteration of the steady-state HDL particle size. Kinetic analysis of time
      dependent changes in NBD fluorescence upon the transition of NBD-labeled apoA-I
      from HDL-bound to lipid-free state indicates that the exchange kinetics are
      independent of the collision frequency between HDL-bound and lipid-free apoA-I,
      in which the lipid binding ability of apoA-I affects the rate of association of
      lipid-free apoA-I with the HDL particles and not the rate of dissociation of HDL
      bound apoA-I. Thus, C-terminal truncations or mutations that reduce the lipid
      binding affinity of apoA-I strongly impair the transition of lipid-free apoA-I to
      the HDL-bound state. Thermodynamic analysis of the exchange kinetics demonstrated
      that the apoA-I exchange process is enthalpically unfavorable but entropically
      favorable. These results explain the thermodynamic basis of the spontaneous
      exchange reaction of apoA-I associated with HDL particles. The altered
      exchangeability of dysfunctional apoA-I would affect HDL particle rearrangement,
      leading to perturbed HDL metabolism. 

PMID- 25564322
TI  - Effects of daikenchuto, a Japanese herb, on intestinal motility after total
      gastrectomy: a prospective randomized trial.
AB  - PURPOSE: This study aimed to assess the efficacy of daikenchuto (DKT), a commonly
      prescribed, traditional Japanese herbal medicine, on postoperative intestinal
      dysfunction after gastric cancer surgery. METHODS: Patients with gastric cancer
      scheduled for a total gastrectomy were randomly assigned before surgery to
      receive either no treatment (n = 40; control group) or DKT (7.5 g/day, t.i.d.)
      for 3 months (n = 41) postoperatively. We examined gastrointestinal motility,
      stool attributes, the quantity of bowel gas, the quality of life, and the
      incidence of postoperative ileus. RESULTS: During the hospital stay, significant
      differences were observed between the DKT group and controls in the number of
      stools per day (1.1 +/- 0.6 vs 0.8 +/- 0.4, respectively; P = 0.037) and stool
      consistencies (Bristol scale ratings were 3.7 +/- 0.8 vs 3.1 +/- 0.8,
      respectively; P = 0.041). The DKT group showed significant reductions in gas
      volume scores, calculated from abdominal radiographs, at 7 days, 1 month, and 3
      months after surgery. The groups did not show significant differences in quality
      of life scores (based on the Gastrointestinal Symptom Rating Scale) or in the
      incidence of postoperative ileus. CONCLUSION: DKT improved bowel movements, stool
      properties, and bowel gas. These results suggested that DKT promoted early
      postoperative bowel functions after total gastrectomy.

PMID- 25564323
TI  - Pancreas-preserving duodenectomy is a safe alternative to high-risk
      pancreatoduodenectomy for premalignant duodenal lesions.
AB  - BACKGROUND: Pancreas-preserving duodenectomy (PPD) can be considered a technical
      alternative to pancreaticoduodenectomy for the treatment of premalignant/low
      grade malignant lesions of the duodenum. However, no many data are available
      comparing surgical results and costs of these two procedures. METHODS:
      Prospectively collected data from the Karolinska University Hospital's electronic
      database was analyzed retrospectively for patients who underwent PD and PPD
      between January 2006 and December 2011. The demographics, length of stay (LOS),
      postoperative morbidity and mortality, and hospital costs were analyzed. RESULTS:
      Twenty patients operated with PPD and 369 with PD were identified. Of the PDs, 81
      were classified as HR-PDs, based on the intraoperative assessment of the gland.
      PPD patients were younger than those with HR-PD (50 vs 62 years; p = 0.0003), and
      with slight prevalence of overweight, BMI >=25 (60 vs 45.7 %; p = 0.2). No
      differences were found in overall morbidity (55 vs 68 %; p = 0.3), in severe
      postoperative complications-Dindo-Clavien grade >=3b (20 vs 30 %; p = 0.3), in
      delayed gastric emptying (10 vs 12 %, ns), and postpancreatectomy hemorrhage (10
      vs 7.4 %, ns) between PPD and HR-PDs. However, the incidence of POPF was
      marginally lower in the PPD group (15 vs 37 %; p = 0.06) and was treated
      conservatively, while ten patients in the HR-PD group were reoperated and with
      POPF-associated mortality of 40 %. Also, shorter ICU stay (5 vs 12.%, ns), lower
      reoperation rate (10 vs 21 %, ns), lower mortality (0 vs 6.2 %), and shorter LOS
      (16.9 vs 24.6 days) were observed with PPD compared to HR-PD, but the numbers did
      not reach statistical significance. PPD was performed with shorter operative time
      (319 vs 418 min; p < 0.0001) and less intra-operative blood loss than HR-PD (521
      vs 1027 ml; p = 0.003). The hospital costs for PPD were significantly lower than
      for HR-PD (29,170 vs 53,080 Euro, p = 0.03) CONCLUSIONS: PPD for resection of
      premalignant and low-grade malignant duodenal lesions in this small series shows
      to be an equivalent alternative to HR-PD, as it can be performed with shorter
      operative time, less intraoperative blood loss, and comparable, even slightly
      better, postoperative outcome and with lower costs.

PMID- 25564324
TI  - Laparoscopic liver resection for lesions adjacent to major vasculature:
      feasibility, safety and oncological efficiency.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic liver resection for lesions adjacent to
      major vasculature can be challenging, and many would consider it a
      contraindication. Recently, however, laparoscopic liver surgeons have been
      pushing boundaries and approached some of these lesions laparoscopically. We
      assessed feasibility, safety and oncological efficiency of this laparoscopic
      approach for these lesions. METHODS: This is a monocenter study (2003-2013)
      describing technique and outcomes of laparoscopic liver resection for lesions
      adjacent to major vasculature: <2 cm from the portal vein (main trunk and first
      division), hepatic arteries or inferior vena cava. RESULTS: Thirty-seven patients
      underwent laparoscopic liver resection (LLR) for a lesion adjacent to major
      vasculature. Twenty-four (65%) resections were for malignant disease and 92% R0
      resections. Conversion occurred in three patients (8%). Mean operative time was
      313 min (standard deviation (SD) +/- 101) and intraoperative blood loss 400 ml
      (IQR 213-700). Clavien-Dindo complications > II occurred in two cases (5%), with
      no mortality. Lesions at <1 cm were larger (7.2 cm (2.7-14) vs. 3 cm (2.5-5), p =
      0.03) and operation time was longer (344 +/- 94 vs. 262 +/- 92 min, p = 0.01)
      than lesions at 1-2 cm from major vasculature. CONCLUSIONS: Lesions <2 cm from
      major hepatic vasculature do not represent an absolute contraindication for LLR
      when performed by experienced laparoscopic liver surgeons in selected patients.

PMID- 25564325
TI  - Biaxial Creep Resistance and Structural Remodeling of the Aortic and Mitral
      Valves in Pregnancy.
AB  - Pregnancy produces rapid, dramatic volume-overload changes to the maternal
      circulation. This paper examines pregnancy-induced structural-mechanical changes
      in bovine aortic and mitral heart valve leaflets. Valve leaflets were harvested
      from non-pregnant heifers and pregnant cows. Dimensions, biaxial extensibility
      and creep resistance were assessed and related to changes in the collagen
      network: histological leaflet and anatomic layer thicknesses plus collagen crimp,
      and biochemical collagen content. Collagen stability and crosslinking were
      assessed thermomechanically. Pregnancy altered both aortic and mitral valve
      leaflets. Both valves demonstrated biphasic changes in leaflet stretch,
      decreasing in early pregnancy and recovering by late pregnancy. Creep in leaflets
      from both valves was minimal and decreased even further with pregnancy in the
      mitral valve. There were valve-specific changes in preconditioning areal
      extension with pregnancy: increasing in the aortic valve and decreasing in the
      mitral valve. Leaflet area increased dramatically (84% aortic, 56% mitral), with
      thickening mainly in the fibrosa, accompanied by increases in collagen content
      (8% aortic, 16% mitral): together suggesting synthesis of new collagen. Collagen
      crimp was almost completely lost in pregnancy, with the denaturation temperature
      decreased by approximately 2  degrees C. Mature and total crosslinking increased,
      curiously without a significant increase in immature crosslinking. Mature aortic
      and mitral heart valve leaflets in the maternal cardiovascular system remodel
      substantially and similarly-despite their different embryological origins.

PMID- 25564326
TI  - Modeling and Analysis of the Viscoelastic Response of the Ankle Ligament Complex
      in Inversion Ankle Sprain.
AB  - Since inversion ankle sprain (IAS) damages ankle ligaments and induces changes in
      their viscoelastic properties, evaluating these properties may provide an
      approach to assess injury. The study purposes were to investigate how the
      viscoelastic properties of the ankle ligament complex can be used to
      quantitatively assess IAS, and to investigate the usefulness of the stretched
      exponential function to analyze the relaxation behavior of the ankle ligament
      complex. Fifteen participants with unilateral IAS and 15 controls were included.
      The relaxation behavior of each ankle was measured by an instrumented anterior
      drawer test, and was then curvefitted by the stretched exponential function. By a
      modeling approach, both parameters of the function were found to be associated
      with the viscous response. Statistical analysis was performed to determine
      differences in these two parameters between sprained and uninjured ankles. It was
      found that sprained ankles exhibited significantly lower viscous response than
      uninjured ankles. No significant difference was found among uninjured ankles. In
      conclusion, by using the viscoelastic properties, sprained ankles were
      successfully differentiated from uninjured ankles. In clinical application, this
      method could be a diagnostic tool for quantitative assessment of IAS injury. The
      stretched exponential function was a useful model to analyze the relaxation
      behavior. 

PMID- 25564333
TI  - Specialist Cohort Event Monitoring studies: a new study method for risk
      management in pharmacovigilance.
AB  - The evolving regulatory landscape has heightened the need for innovative,
      proactive, efficient and more meaningful solutions for 'real-world' post
      authorization safety studies (PASS) that not only align with risk management
      objectives to gather additional safety monitoring information or assess a pattern
      of drug utilization, but also satisfy key regulatory requirements for marketing
      authorization holder risk management planning and execution needs. There is a
      need for data capture across the primary care and secondary care interface, or
      for exploring use of new medicines in secondary care to support conducting PASS.
      To fulfil this need, event monitoring has evolved. The Specialist Cohort Event
      Monitoring (SCEM) study is a new application that enables a cohort of patients
      prescribed a medicine in the hospital and secondary care settings to be
      monitored. The method also permits the inclusion of a comparator cohort of
      patients receiving standard care, or another counterfactual comparator group, to
      be monitored concurrently, depending on the study question. The approach has been
      developed in parallel with the new legislative requirement for pharmaceutical
      companies to undertake a risk management plan as part of post-authorization
      safety monitoring. SCEM studies recognize that the study population comprises
      those patients who may have treatment initiated under the care of specialist
      health care professionals and who are more complex in terms of underlying
      disease, co-morbidities and concomitant medications than the general disease
      population treated in primary care. The aims of this paper are to discuss the
      SCEM new-user study design, rationale and features that aim to address possible
      bias (such as selection bias) and current applications. 

PMID- 25564327
TI  - Frequency-Dependence of Mechanically Stimulated Osteoblastic Calcification in
      Tissue-Engineered Bone In Vitro.
AB  - The effect of mechanical stimulation on osteogenesis remains controversial,
      especially with respect to the loading frequency that maximizes osteogenesis.
      Mechanical stimulation at an optimized frequency may be beneficial for the bone
      tissue regeneration to promote osteoblastic calcification. The objective of this
      study was to investigate the frequency-dependent effect of mechanical loading on
      osteoblastic calcification in the tissue-engineered bones in vitro. Tissue
      engineered bones were constructed by seeding rat osteoblasts into a type I
      collagen sponge scaffold at a cell density of 1600 or 24,000 cells/mm(3).
      Sinusoidal compressive deformation at the peak of 0.2% was applied to the tissue
      engineered bones at 0.2, 2, 10, 20, 40, and 60 Hz for 3 min/day for 14
      consecutive days. Optically-monitored calcium content started to increase on days
      5-7 and reached the highest value at 2 Hz on day 14; however, no increase was
      observed at 0.2 Hz and in the control. Ash content measured after the mechanical
      stimulation also showed the highest at 2 Hz despite the differences in cell
      seeding density. It was concluded that mechanical stimulation at 2 Hz showed the
      highest promotional effect for osteogenesis in vitro among the frequencies
      selected in this study. 

PMID- 25564334
TI  - Obstetrical staff nurses experiences of clinical learning.
AB  - The clinical learning experience is used in nursing programs of study worldwide
      to prepare nurses for professional practice. This study's purpose was to use
      Naturalistic Inquiry to understand the experiences of staff nurses in an
      obstetrical unit with undergraduate nursing students present for clinical
      learning. A convenience sample of 12 staff nurses, employed on a Family Birth
      Center, participated in semi-structured interviews. The constant comparative
      method as modified by Lincoln and Guba was used to analyze data. Five themes
      related to staff nurses experiences of clinical learning were identified: Giving
      and Receiving; Advancing Professionally and Personally; Balancing Act; Getting to
      Know and Working with You; and Past and Present. This research highlights staff
      nurses' experiences of clinical learning in undergraduate nursing education.
      Staff nurses exert a powerful, long lasting influence on students. A need exists
      to prepare and judiciously select nurses to work with students. Clinical agencies
      and universities can take joint responsibility providing tangible incentives,
      financial compensation, and recognition to all nurses working with nursing
      students. 

PMID- 25564335
TI  - Efficacy of chandelier illumination for combined cataract operation and
      penetrating keratoplasty.
AB  - PURPOSE: The aim of this study was to describe a method for non-open-sky
      continuous curvilinear capsulorhexis (CCC) with chandelier retroillumination for
      penetrating keratoplasty triple procedure and report its effectiveness in
      decreasing intraoperative complications and enabling successful primary
      intraocular lens (IOL) insertion in patients with moderate or dense central
      corneal opacities. METHODS: Seventeen eyes of 17 patients were enrolled in this
      study, divided into a chandelier group, including 7 eyes of 7 patients, and a
      nonchandelier group, including 10 eyes of 10 patients. In each group, time to
      achieve CCC (in seconds), open-sky time (in seconds), and operation time (in
      minutes) were measured, and the rates of successful CCC completion, rupture of
      the posterior capsule or zonule of Zinn, and successful IOL insertion were
      recorded. RESULTS: CCC time was not significantly different in both groups. In
      the chandelier group, however, open-sky time and operation time were
      significantly shorter than in the nonchandelier group (1429 +/- 67 vs. 2016 +/-
      354 seconds, and 90.4 +/- 3.5 vs. 108.9 +/- 10.3 minutes, respectively). In the
      chandelier group, the rate of successful CCC completion was significantly higher
      than in the nonchandelier group (86% vs. 30%). The rates of posterior capsule or
      zonule of Zinn rupture and successful IOL insertion were not significantly
      different (14% vs. 40%, 14% vs. 10%, and 86% vs. 70%, respectively). CONCLUSIONS:
      Non-open-sky CCC with chandelier illumination has many advantages for penetrating
      keratoplasty triple procedure compared with open-sky CCC without chandelier
      illumination.

PMID- 25564336
TI  - IC3D classification of corneal dystrophies--edition 2.
AB  - PURPOSE: To update the 2008 International Classification of Corneal Dystrophies
      (IC3D) incorporating new clinical, histopathologic, and genetic information.
      METHODS: The IC3D reviewed worldwide peer-reviewed articles for new information
      on corneal dystrophies published between 2008 and 2014. Using this information,
      corneal dystrophy templates and anatomic classification were updated. New
      clinical, histopathologic, and confocal photographs were added. RESULTS: On the
      basis of revisiting the cellular origin of corneal dystrophy, a modified anatomic
      classification is proposed consisting of (1) epithelial and subepithelial
      dystrophies, (2) epithelial-stromal TGFBI dystrophies, (3) stromal dystrophies,
      and (4) endothelial dystrophies. Most of the dystrophy templates are updated. The
      entity "Epithelial recurrent erosion dystrophies" actually includes a number of
      potentially distinct epithelial dystrophies (Franceschetti corneal dystrophy,
      Dystrophia Smolandiensis, and Dystrophia Helsinglandica) but must be
      differentiated from dystrophies such as TGFBI-induced dystrophies, which are also
      often associated with recurrent epithelial erosions. The chromosome locus of
      Thiel-Behnke corneal dystrophy is only located on 5q31. The entity previously
      designated as a variant of Thiel-Behnke corneal dystrophy on chromosome 10q24 may
      represent a novel corneal dystrophy. Congenital hereditary endothelial dystrophy
      (CHED, formerly CHED2) is most likely only an autosomal recessive disorder. The
      so-called autosomal dominant inherited CHED (formerly CHED1) is insufficiently
      distinct to continue to be considered a unique corneal dystrophy. On review of
      almost all of the published cases, the description appeared most similar to a
      type of posterior polymorphous corneal dystrophy linked to the same chromosome 20
      locus (PPCD1). Confocal microscopy also has emerged as a helpful tool to reveal
      in vivo features of several corneal dystrophies that previously required
      histopathologic examination to definitively diagnose. CONCLUSIONS: This revision
      of the IC3D classification includes an updated anatomic classification of corneal
      dystrophies more accurately classifying TGFBI dystrophies that affect multiple
      layers rather than are confined to one corneal layer. Typical histopathologic and
      confocal images have been added to the corneal dystrophy templates.

PMID- 25564337
TI  - Inhibitory effect of baicalin, baicalein and wogonin on secretory group IIA
      phospholipase A2.
AB  - It is well known that the expression level of secretory group IIA phospholipase
      A2 (sPLA2-IIA) is elevated in inflammatory diseases and lipopolysaccharide (LPS)
      up-regulates the expression of sPLA2-IIA in human umbilical vein endothelial
      cells (HUVECs). Here, three structurally related polyphenols found in the Chinese
      herb Huang Qui, namely baicalin, baicalein, and wogonin, were examined for its
      effects on the expression and activity of sPLA2-IIA in HUVECs and mouse. Prior
      treatment of cells or mouse with baicalin, baicalein, and wogonin inhibited LPS
      induced expression and activity of sPLA2-IIA. And each compound suppressed the
      activation of cytosolic phospholipase A2 (cPLA2) and extracellular signal
      regulated kinase (ERK) 1/2 by LPS. Therefore, these results suggest that
      baicalin, baicalein, and wogonin inhibited LPS mediated expression of sPLA2-IIA
      by suppression of cPLA2 and ERK 1/2. 

PMID- 25564338
TI  - Development of in-cell imaging assay systems for MMP-2 and MMP-9 based on trans
      localizing molecular beacon proteins.
AB  - A sensitive in-cell imaging MMP-2 and MMP-9 detection systems that enables direct
      fluorescence detection of a target protease and its inhibition inside living
      cells has been developed. This in-cell imaging system utilizes the concept of
      fluorescent molecular beacon reporter (MBR) protein comprising a masking protein,
      a mitochondrial targeting sequence, a protease specific cleavage sequence and a
      fluorescent marker sequence, green fluorescent protein (GFP). The MBR protein is
      designed to change its intracellular location upon cleavage by either MMP-2 or
      MMP-9 from cytosol to mitochondria. Full and partial MMP-2 and MMP-9 were tested
      for optimal expression and activity in the cell. The activity of MMP-2 and MMP-9
      was approximately 65-71%. Among MMP clones, MMP-2 catalytic domain and MMP-9
      clone containing pro, catalytic and hemopexin domain were most active. Both MMP-2
      and MMP-9 required divalent ions Ca and Zn for its activity and MMP-9 was more
      active at higher Ca/Zn ratio. With the in-cell imaging assay the protease
      activity can be measured in cellular environment and cellular toxicity of
      candidate molecules can be monitored at the same time. These are great advantage
      when compared to other currently used in vitro biochemical assays. The in-cell
      imaging assay developed in this study can be modified for other MMPs and can be
      used in various life science and drug discovery researches including the high
      throughput screening and high contents screening applications.

PMID- 25564339
TI  - Glucocorticoid- and long-term stress-induced aberrant synaptic plasticity are
      mediated by activation of the glucocorticoid receptor.
AB  - Long-term stress is known to cause aberrant synaptic plasticity and to impair
      learning and memory. Recent studies show that acute high concentration of
      glucocorticoids exerts similar effects to those of long-term stress. In the
      present study, we conducted an electrophysiological study, western blot analysis,
      and behavioral study to examine whether long-term stress and acute high
      concentration of corticosterone share common mechanisms. Acute corticosterone (1
      MUM) impaired LTP in the acute hippocampal slices, and this impairment was
      blocked by RU486, a glucocorticoid receptor (GR) antagonist. In the two-week
      restraint stress-treated rats, object recognition memory and hippocampal LTP were
      impaired and these impairments were restored by RU486 co-treatment. Moreover, the
      hippocampal BDNF level was also significantly reduced in the corticosterone- or
      long-term stress-treated hippocampus and restored by RU486 co-treatment. These
      results suggest that corticosterone and long-term stress induce aberrant synaptic
      plasticity, memory impairment, and reduction in the hippocampal BDNF level
      through GR activation. Taken together, we suggest that acute high concentration
      of glucocorticoid-induced LTP impairment study may be a good tool for screening
      the treatments for stress-induced psychiatric disorders including memory
      impairment.

PMID- 25564340
TI  - Assessing lung cancer incidence disparities between Puerto Ricans and other
      racial/ethnic groups in the United States, 1992-2010.
AB  - This study compared the incidence of lung cancer among Puerto Ricans (PRs) with
      that of Whites, Blacks, and Hispanics in the United States. We computed age
      standardized rates of lung cancer during 1992-2010 and percentages of change over
      time. Standardized rate ratios (SRR) were estimated to assess racial/ethnic and
      gender differences. All men groups showed a significant decline in lung cancer
      over time but PRs observed the smallest change (-1.2%). For both men and women,
      PRs had lower incidence rates compared to other racial/ethnic groups (SRR < 1; P
      < 0.05). Among all groups, men reported higher incidence rates than women but PRs
      showed the largest gender disparity (SRR = 2.29). This study showed that although
      PRs exhibited lower incidence rates of lung cancer, this subgroup of Hispanics
      faced an important burden of lung cancer, principally because PR men had the
      smallest decline over time and the largest gender difference among all groups.

PMID- 25564341
TI  - Healthy Migrant Effect on Smoking Behavior Among Asian Immigrants in the United
      States.
AB  - Healthy migrant effect (HME) of immigrants has been evidenced in various heath
      aspects. However, few studies have explored the applicability of HME on Asian
      immigrants' health risk behavior-smoking. This study used three waves of Current
      Population Survey-Tobacco Use Supplement data, 1998-1999, 2005-2006, and 2010
      2011, to compare the rates of being a current smoker among Asian immigrants and
      United States born citizens. Further, the odds ratios of gender, age, marital
      status, socioeconomic status, years of migration, and citizenship status on the
      likelihood of being a current smoker were examined. Across the three waves, Asian
      immigrants smoked at a much lower rate than their native-born counterparts. The
      gender gap of being a current smoker was much wider among Asian immigrants. The
      longer the Asian immigrants stayed in the United States, the more likely they
      were to become current smokers. These data confirmed the association of HME and
      Asian immigrants' smoking behavior, and also provided strong evidence of the
      importance of smoking prevention among Asian immigrants. This study also implied
      the possibility of a decline in the effectiveness of HME on Asian immigrants as
      the time they spent in the United States increased. 

PMID- 25564342
TI  - Microbiology of diabetic foot infections: from Louis Pasteur to 'crime scene
      investigation'.
AB  - Were he alive today, would Louis Pasteur still champion culture methods he
      pioneered over 150 years ago for identifying bacterial pathogens? Or, might he
      suggest that new molecular techniques may prove a better way forward for quickly
      detecting the true microbial diversity of wounds? As modern clinicians faced with
      treating complex patients with diabetic foot infections (DFI), should we still
      request venerated and familiar culture and sensitivity methods, or is it time to
      ask for newer molecular tests, such as 16S rRNA gene sequencing? Or, are
      molecular techniques as yet too experimental, non-specific and expensive for
      current clinical use? While molecular techniques help us to identify more
      microorganisms from a DFI, can they tell us 'who done it?', that is, which are
      the causative pathogens and which are merely colonizers? Furthermore, can
      molecular techniques provide clinically relevant, rapid information on the
      virulence of wound isolates and their antibiotic sensitivities? We herein review
      current knowledge on the microbiology of DFI, from standard culture methods to
      the current era of rapid and comprehensive 'crime scene investigation' (CSI)
      techniques.

PMID- 25564343
TI  - Nano-size uni-lamellar lipodisq improved in situ auto-phosphorylation analysis of
      E. coli tyrosine kinase using (19)F nuclear magnetic resonance.

PMID- 25564344
TI  - Prospective phase II trial of nimotuzumab in combination with radiotherapy and
      concurrent capecitabine in locally advanced rectal cancer.
AB  - PURPOSE: The aim of the study was to evaluate the safety and efficacy of adding
      concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine
      in locally advanced rectal cancer. METHODS AND MATERIALS: Patients with rectal
      cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab
      (400 mg; days -6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m(2)) was delivered
      orally twice daily for the duration of radiotherapy. Radiotherapy was
      administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic
      complete response (pCR) rate. RESULTS: Twenty-one patients with T3 or T4 disease
      were enrolled; 66.7 % were nodal-positive; the median distance from the anal
      verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients
      obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred
      in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual
      dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine
      (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis
      (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %),
      and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and
      Grade 3 leukocytopenia in 4.8 %. CONCLUSION: These preliminary results indicate
      that nimotuzumab can be safely combined with radiotherapy plus concurrent
      capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly
      higher than that observed in previous phase II trials of preoperative
      radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further
      investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is
      warranted.

PMID- 25564346
TI  - Intestinal obstruction due to axial torsion of a giant Meckel's diverticulum: a
      case report.

PMID- 25564345
TI  - Radiation therapy in patients with inflammatory bowel disease and colorectal
      cancer: risks and benefits.
AB  - PURPOSE: The effects of radiotherapy are debated in inflammatory bowel disease
      (IBD). We examined IBD patients with colorectal cancer (CRC) and compared those
      who underwent external beam radiation therapy (EBRT) to those who did not. We
      then compared those same patients treated with EBRT to similarly treated non-IBD
      patients to ascertain differences in toxicity and perioperative outcomes.
      METHODS: Fifty-seven IBD patients with CRC received EBRT, of which 23 had
      perioperative follow-up and 15 had complete records. The 23 patients were
      compared to 229 IBD patients with CRC who did not receive EBRT. The 15 patients
      were matched, 1:2, to similarly treated non-IBD patients with CRC based on age
      (+/-5 years), treatment year (+/-1 year), BMI (+/-10 kg/m2), and clinical stage.
      RESULTS: There was significantly more postoperative bleeding (5.3 % vs. 0 %, p <
      0.01), wound dehiscence (3.5 % vs. 0 %, p < 0.01), and perineal infection (8.8 %
      vs. 1.3 %, p < 0.01) in IBD patients with EBRT compared to those without EBRT.
      IBD patients were significantly more likely to have grade 3 or higher lower GI
      toxicity (40 % vs. 7 %, p = 0.02) and wound dehiscence (36 % vs. 7 %, p = 0.02)
      than non-IBD patients, however without significant difference in bleeding,
      infection, ileus, or survival. CONCLUSION: IBD patients with CRC who received
      EBRT were more likely than similar patients without EBRT to experience
      perioperative complications. These patients also experienced more lower GI
      toxicity than similarly treated non-IBD patients with CRC. The expected decrease
      in survival in IBD-associated CRC was not observed. Thus, EBRT may contribute to
      a survival benefit in this group.

PMID- 25564347
TI  - Colonic metastases from gastric adenocarcinoma.

PMID- 25564348
TI  - Adenocarcinoma of the ileal pouch mucosa: a new diagnostic challenge.

PMID- 25564349
TI  - Successful use of adalimumab to treat pyoderma gangrenosum, acne and suppurative
      hidradenitis (PASH syndrome) following colectomy in ulcerative colitis.

PMID- 25564350
TI  - Anterior approach unilateral right sacrospinous fixation for recurrent pelvic
      organ prolapse following multiple colorectal surgeries.

PMID- 25564351
TI  - LNA units present in the (2'-OMe)-RNA strand stabilize parallel duplexes (2'-OMe)
      RNA/[All-R(P)-PS]-DNA and parallel triplexes (2'-OMe)-RNA/[All-R(P)-PS]-DNA/RNA.
      An improved tool for the inhibition of reverse transcription.
AB  - Homopurine phosphorothioate analogs of DNA, possessing all phosphorus atoms of RP
      configuration ([All-RP-PS]-DNA), when interact with appropriate complementary RNA
      or (2'-OMe)-RNA templates, form parallel triplexes or parallel duplexes of very
      high thermodynamic stability. The present results show that T-LNA or 5-Me-C-LNA
      units introduced into the parallel Hoogsteen-paired (2'-OMe)-RNA strands (up to
      four units in the oligomers of 9 or 12 nt in length) stabilize these parallel
      complexes. At neutral pH, dodecameric parallel duplexes have Tm values of 62-68 
      degrees C, which are by 4-10  degrees C higher than Tm for the reference duplex
      (with no LNA units present), while for the corresponding triplexes, Tm values
      exceeded 85  degrees C. For nonameric parallel duplexes, melting temperatures of
      38-62  degrees C were found and (2'-OMe)-RNA oligomers containing 5-Me-C-LNA
      units stabilized the complexes more efficiently than the T-LNA containing
      congeners. In both series the stability of the parallel complexes increased with
      an increasing number of LNA units present. The same trend was observed in
      experiments of reverse transcription RNA->DNA (using AMV RT reverse
      transcriptase) where the formation of parallel triplexes (consisting of an RNA
      template, [All-RP-PS]-DNA nonamer and Hoogsteen-paired (2'-OMe)-RNA strands
      containing the LNA units) led to the efficient inhibition of the process. Under
      the best conditions checked (four 5-Me-C-LNA units, three-fold excess over the
      RNA template) the inhibition was 94% effective, compared to 71% inhibition
      observed in the reference system with the Hoogsteen-paired (2'-OMe)-RNA strand
      carrying no LNA units. This kind of complexation may "arrest" harmful RNA
      oligomers (e.g., viral RNA or mRNA of unwanted proteins) and, beneficially,
      exclude them from enzymatic processes, otherwise leading to viral or genetic
      diseases. 

PMID- 25564352
TI  - Contact heat evoked potentials and habituation measured interictally in
      migraineurs.
AB  - BACKGROUND: A lack of habituation of different evoked potential modalities in
      migraine patients in-between attacks has been suggested. METHODS: This study
      investigates cortical response after painful stimuli evaluated by contact heat
      evoked potentials (CHEPs) and quantitative sensory testing (QST) during the
      migraine-free interval. We enrolled 22 migraine patients and 22 healthy subjects.
      RESULTS: Cortical potentials after contact heat stimulation of the cheeks and the
      volar forearm at a temperature of 51 degrees C showed significantly reduced A
      delta-amplitudes in patients and healthy controls. When the subjects' attention
      was drawn to an arithmetic task, a partial lack of habituation of amplitude could
      be seen in migraine patients. QST did not show any difference between migraineurs
      and controls. CONCLUSION: Our findings can be primarily deemed to demonstrate
      that patients and healthy controls show significantly lower amplitudes while
      performing the calculation task. Without performing the calculation task we could
      not show the expected lack of habituation in migraineurs. Yet, while performing
      the calculation task our results partly suggest that hypothesis.

PMID- 25564355
TI  - Expression and clinical role of TCTP in epithelial ovarian cancer.
AB  - The aim of this study is to investigate the potential role and prognostic
      significance of translationally controlled tumor protein (TCTP) in human
      epithelial ovarian cancer (EOC). Western blot was used to evaluate the expression
      of TCTP in eight fresh EOC tissues. Immunohistochemistry was performed on
      formalin-fixed paraffin-embedded sections of 119 cases of ovarian cancers. Kaplan
      Meier method indicated the relation between TCTP and EOC patients' overall
      survival rate. Starvation and re-feeding was used to assess cell cycle. Knocking
      down of TCTP and CCK8 assay showed the role of TCTP in HO8910 cell cycle. We
      found that TCTP was overexpressed in carcinoma tissues compared with normal
      tissues. Immunohistochemistry revealed that TCTP expression was significantly
      associated with clinicopathologic variables. Kaplan-Meier analysis revealed that
      high TCTP expression was significantly related to poor prognosis of the patients.
      Starvation and re-feeding suggested TCTP played a critical role in HO8910 cell
      proliferation. Interference of TCTP and CCK8 assay showed that the TCTP-siRNA
      treated HO8910 cells grew more slowly than the control group. CCK-8 assays and
      terminal-deoxynucleoitidyl transferase mediated nick end labeling assays were
      also performed to demonstrate the cisplatin could inhibit the survival of HO8910
      cells and promote their apoptosis. All the experiments we have done showed that
      TCTP could promote the progression of EOC and reduce the sensitiveness of HO8910
      cells to cisplatin. 

PMID- 25564353
TI  - Insights into structural and functional diversity of Dof (DNA binding with one
      finger) transcription factor.
AB  - MAIN CONCLUSION: The structural, functional and in-silico studies of Dof
      transcription factor attempted so far reveals immense opportunity to analyze the
      plant genomes in terms of number of Dof genes and discuss in light of the
      evolution. The multiple functions of Dof genes needs to explored for crop
      improvement. Transcription factors play a very vital role in gene regulation at
      transcriptional level and are being extensively studied across phylas. In recent
      years, sequencing of plant genomes has led to genome-wide identification and
      characterizations of diverse types of plant-specific transcription factor gene
      family providing key insights into their structural and functional diversity. The
      DNA binding with one finger (Dof), a class belonging to C2H2-type zinc finger
      family proteins, is a plant-specific transcription factor having multiple roles
      such as seed maturation and germination, phytohormone and light-mediated
      regulation and plant responses to biotic and abiotic stresses. Dof proteins are
      present across plant lineage, from green algae to higher angiosperm, and
      represent a unique class of transcription factor having bifunctional binding
      activities, with both DNA and proteins, to regulate the complex transcriptional
      machinery in plant cells. The structural and functional diversity of the Dof
      transcription factor family along with the bioinformatics analysis highlighting
      the phylogeny of Dof families is reviewed in light of its importance in plant
      biotechnology for crop improvement.

PMID- 25564356
TI  - Downregulation of angiogenin inhibits the growth and induces apoptosis in human
      bladder cancer cells through regulating AKT/mTOR signaling pathway.
AB  - Angiogenin (ANG) is a multifunctional secreted protein that belongs to the
      pancreatic ribonuclease A super family, which has been conceived to play a more
      important role in cell survival, growth and proliferation than the mediation of
      angiogenesis. Accumulating evidences suggest that the expression and activity of
      ANG increased significantly in a variety of human cancers. Recent studies showed
      that ANG activates cell signaling pathway through the putative receptor on
      endothelial cells. However, the underlying mechanisms remain largely unknown.
      AKT/mTOR signaling pathway participates in cell growth, cell-cycle progression
      and cell apoptosis. The purpose of our study was to determine whether ANG
      implicated in growth and metastasis of bladder cancer cells through regulating
      AKT/mTOR signaling pathway. In this study, we constructed ANG siRNA plasmids that
      transfected into human bladder cancer T24 cells. We demonstrated that knockdown
      of ANG could inhibit cell proliferation, regulate cell cycle and induce
      apoptosis. We also found that down-regulation of ANG remarkably reduced the
      phosphorylation of signaling targets AKT, GSK-3beta and mTOR. Furthermore, down
      regulation of ANG increased expression of ribonuclease inhibitor, which is a
      cytoplasmic acidic protein with many functions. Finally, ANG siRNA led to the
      suppression for tumorigenesis and metastasis in vivo. Taken together, these
      findings highlight for the first time that ANG could play a pivotal role in the
      development of bladder cancer through regulating AKT/mTOR signaling pathway. The
      targeting of ANG and associated factors could provide a novel strategy to inhibit
      human bladder cancer. 

PMID- 25564358
TI  - Clinical Analysis of Internal Fixation Treatment of Intra-articular Calcaneal
      Fractures with Titanium Plate.
AB  - To explore the clinical effect of internal fixation treatment of intra-articular
      calcaneal fractures with titanium plate, we used open reduction and internal
      fixation with titanium plate to 48 treated feet from 42 patients with intra
      articular calcaneal fractures. The efficacy of surgical treatment was evaluated
      based on assessment of pain, function, and line of force aspects according to the
      American Orthopedic Foot and Ankle Society scoring system. Our data show that
      internal fixation with titanium plate is an effective treatment for calcaneal
      fractures. It provides satisfactory reduction, reliable fixation, and early
      rehabilitation. 

PMID- 25564357
TI  - The Association Between Modic Changes of Lumbar Endplates and Spontaneous
      Absorption of Herniated Intervertebral Discs.
AB  - Herniated disc (HD) is one of the most common causes of lower back pain.
      Treatment for HD includes conservative therapy and surgical intervention.
      Following conservative treatment, spontaneous absorption of HD occurs in some
      patients. To assess whether modic changes are associated with spontaneous
      absorption of HD, 85 patients with or without modic changes were followed up
      after 6 months of conservative treatment. As result, we found modic changes of
      lumbar endplates are associated with poor absorption of HD after conservative
      treatment. In addition, patients with modic changes exhibit significantly
      increased cartilage content and decreased neovascularization and macrophage
      infiltration in HD tissues, all of which are known to impair spontaneous
      absorption of herniated tissues. At molecular level, modic changes are associated
      with decreased expression of matrix metalloproteinase-3 gene, which is a key
      matrix-degrading enzyme for tissue absorption. Our study established a strong
      association between modic changes of lumbar endplates and spontaneous absorption
      of lumbar HD, which provided a potential novel method for prediction of
      spontaneous absorption. 

PMID- 25564359
TI  - Duodenal Neuroendocrine Carcinoma Presenting with Disseminated Liver and Bone
      Metastases as the Primary Manifestation: Case Report and Literature Review.
AB  - Neuroendocrine tumors are composed by a heterogeneous group of tumors with a wide
      range of morphologic, functional, and behavioral characteristics. These tumors
      are generally slow growing and behave in an indolent fashion. However, they have
      the potential to spread, especially for poorly differentiated neuroendocrine
      carcinomas, and when they do, they can be very aggressive, with high propensity
      for distant metastases, and difficult to treat with current modalities. As poorly
      differentiated neuroendocrine carcinomas rarely occur in extrapulmonary sites, to
      the best of our knowledge, this is the first case report of a poorly
      differentiated duodenal neuroendocrine carcinoma with diffuse liver and bone
      metastases as the primary manifestation. Despite receiving a trial of
      chemotherapeutic regimen, the patient had progressive intrahepatic cholestasis
      and died of subacute hepatic failure. 

PMID- 25564360
TI  - Synthetic miR-145 Mimic Enhances the Cytotoxic Effect of the Antiangiogenic Drug
      Sunitinib in Glioblastoma.
AB  - Although aggressive therapeutic regimen has been applied in the treatment of
      Glioblastoma (GBM), the prognosis of patients with GBM remains poor. Preclinical
      studies have demonstrated the efficacy of Suntinib in GBM both in vitro and in
      vivo. In this study, we showed that the cytotoxicity was enhanced by transfection
      with miR-145 mimic. In addition, we suggested that the enhanced cytotoxicity of
      Sunitinib by miR-145 mimic was mediated by inhibition of both P-gp and Bcrp. 

PMID- 25564361
TI  - Perioperative concerns in a beta-ketothiolase-deficient child.

PMID- 25564362
TI  - Mimosa caesalpiniifolia rhizobial isolates from different origins of the
      Brazilian Northeast.
AB  - Biological nitrogen fixation from the legume-rhizobia symbiosis is one of the
      main sources of fixed nitrogen on land environments. Diazotrophic bacteria
      taxonomy has been substantially modified by the joint use of phenotypic,
      physiological and molecular aspects. Among these molecular tools, sequencing and
      genotyping of genomic regions such as 16S rDNA and repetitive conserved DNA
      regions have boosted the accuracy of species identification. This research is a
      phylogenetic study of diazotrophic bacteria from sabia (Mimosa caesalpiniifolia
      Benth.), inoculated with soils from five municipalities of the Brazilian
      Northeast. After bacterial isolation and morphophysiological characterization,
      genotyping was performed using REP, ERIC and BOX oligonucleotides and 16S rDNA
      sequencing for genetic diversity identification. A 1.5b Kb fragment of the 16S
      rDNA was amplified from each isolate. Morphophysiological characterization of the
      47 isolates created a dendrogram, where isolate PE-GR02 formed a monophyletic
      branch. The fingerprinting conducted with BOX, ERIC and REP shows distinct
      patterns, and their compilation created a dendrogram with diverse groups and,
      after blasting in GenBank, resulted in genetic identities ranging from 77 to 99 %
      with Burkholderia strains. The 16S rDNA phylogenetic tree constructed with these
      isolates and GenBank deposits of strains recommended for inoculant production
      confirm these isolates are distinct from the previously deposited strains,
      whereas isolates PE-CR02, PE-CR4, PE-CR07, PE-CR09 and PE-GE06 were the most
      distinct within the group. Morphophysiological characterization and BOX, ERIC and
      REP compilation enhanced the discrimination of the isolates, and the 16S rDNA
      sequences compared with GenBank confirmed the preference of Mimosa for
      Burkholderia diazotrophic bacteria. 

PMID- 25564363
TI  - Determination of phosphite in a full-scale municipal wastewater treatment plant.
AB  - Phosphite (HPO3(2-), +3), a reduced P species in the P biogeochemical cycle, was
      monitored in a full-scale municipal wastewater treatment plant (MWTP) that uses
      an anaerobic/anoxic/aerobic-membrane bioreactor (A(2)/O-MBR) technology for
      treating mixed wastewater (56% industrial wastewater and 44% domestic wastewater)
      from June 2013 to May 2014. Wastewater samples were collected from influent after
      having gone through the fine grille, anaerobic tank, anoxic tank, and aerobics
      tank, respectively. The final stage yielded effluent. Results confirmed the
      presence of phosphite in the MWTP ranging from 4.62 +/- 1.00 MUg P L(-1) to 34.30
      +/- 3.49 MUg P L(-1) in influent and from 1.15 +/- 0.5 MUg P L(-1) to 4.42 +/-
      0.9 MUg P L(-1) in effluent. Phosphite accounted for approximately 0.15% to 2.27%
      of total soluble phosphorus (TSP). During the A(2)/O-MBR process, the average
      removal of phosphite was 82.41 +/- 7.45%. The anaerobic biological treatment
      removed the most phosphite from wastewater in this study. Spatially, phosphite
      concentrations decreased gradually as the wastewater treatment process
      progressed. Seasonally, the phosphite concentrations in spring and winter were
      higher than those in summer and autumn. The phosphite concentration in effluent
      was of the same order of magnitude as that in nearby natural water, which
      suggested MWTP effluent may be an important phosphite contributor to the natural
      water. 

PMID- 25564364
TI  - Molecular analysis of the caecal and tracheal microbiome of heat-stressed
      broilers supplemented with prebiotic and probiotic.
AB  - The gastrointestinal tract commensal microbiome is important for host nutrition,
      health and immunity. Little information is available regarding the role of these
      commensals at other mucosal surfaces in poultry. Tracheal mucosal surfaces offer
      sites for first-line health and immunity promotion in broilers, especially under
      stress-related conditions. The present study is aimed at elucidating the effects
      of feed supplementations with mannanoligosaccharides (MOS) prebiotic and a
      probiotic mixture (PM) on the caecal and tracheal microbiome of broilers kept
      under chronic heat stress (HS; 35 +/- 2 degrees C). Day-old chickens were
      randomly divided into five treatment groups: thermoneutral control (TN-CONT), HS
      CONT, HS-MOS, HS-PM and HS synbiotic (fed MOS and PM). Caecal digesta and
      tracheal swabs were collected at day 42 and subjected to DNA extraction, followed
      by polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE)
      and pyrosequencing. The PCR-DGGE dendrograms revealed significant (49.5%
      similarity coefficients) differences between caecal and tracheal microbiome.
      Tracheal microbiome pyrosequencing revealed 9 phyla, 17 classes, 34 orders, 68
      families and 125 genera, while 11 phyla, 19 classes, 34 orders, 85 families and
      165 genera were identified in caeca. An unweighted UniFrac distance metric
      revealed a distinct clustering pattern (analysis of similarities, P = 0.007)
      between caecal and tracheal microbiome. Lactobacillus was the most abundant genus
      in trachea and caeca and was more abundant in caeca and trachea of HS groups
      compared with the TN-CONT group. Distinct bacterial clades occupied the caecal
      and tracheal microbiomes, although some bacterial groups overlapped,
      demonstrating a core microbiome dominated by Lactobacillus. No positive effects
      of supplementations were observed on abundance of probiotic bacteria. 

PMID- 25564365
TI  - Lymphatic pathway around the pancreatic head and extrahepatic bile duct:
      evaluation using MR imaging at 3.0-T.
AB  - PURPOSE: To evaluate the utility of spectral presaturation with inversion
      recovery (SPIR) T2-weighted images with 3-dimensional (3D) volume isotropic turbo
      spin echo acquisition (VISTA) at 3.0-T for the detection of the normal lymphatic
      systems located around the pancreatic head and extrahepatic bile duct. MATERIALS
      AND METHODS: Fifty-six patients with suspected hepatic or pancreaticobiliary
      diseases and diagnosed as normal or benign pathologies were evaluated as having
      normal lymphatic systems. The protocol consisted of SPIR T2-weighted sequences
      with 3D-VISTA. The lymphatic systems were defined as fluid signal intensity
      structures and divided into eight portions and interobserver agreement was
      evaluated using weighted kappa statistics. Three readers graded the visualization
      of each portion using a five-point scale. The detectability of each portion was
      calculated by defining grades 1-2 as detectable and grades 3-5 as undetectable.
      RESULTS: Interobserver agreement regarding the visualization grades was moderate
      to almost perfect. All readers rated the detectability of the lymphatic systems
      of the superior and posterior portions of the pancreatic head, pericholedochal,
      right abdominoaortic, and interaorticovenous portions as 100%, and that of the
      anterior portion of the pancreatic head as 98.2%. For the inferior portion of the
      pancreatic head, the detectability was 100% for reader 2 and 96.4% for readers 1
      and 3. CONCLUSION: The lymphatic systems located around the pancreatic head and
      extrahepatic bile duct could be sufficiently visualized on SPIR T2-weighted
      images with 3D-VISTA at 3.0-T.

PMID- 25564366
TI  - Polarization response of nanowires a la carte.
AB  - Thanks to their special interaction with light, semiconductor nanowires have
      opened new avenues in photonics, quantum optics and solar energy harvesting. One
      of the major challenges for their full technological deployment has been their
      strong polarization dependence in light absorption and emission. In the past,
      metal nanostructures have been shown to have the ability to modify and enhance
      the light response of nanoscale objects. Here we demonstrate that a hybrid
      structure formed by GaAs nanowires with a highly dense array of bow-tie antennas
      is able to modify the polarization response of a nanowire. As a result, the
      increase in light absorption for transverse polarized light changes the nanowire
      polarization response, including the polarization response inversion. This work
      will open a new path towards the widespread implementation of nanowires
      applications such as in photodetection, solar energy harvesting and light
      emission. 

PMID- 25564367
TI  - Recombinant protein (EGFP-Protein G)-coated PbS quantum dots for in vitro and in
      vivo dual fluorescence (visible and second-NIR) imaging of breast tumors.
AB  - We report a one-step synthetic strategy for the preparation of recombinant
      protein (EGFP-Protein G)-coated PbS quantum dots for dual (visible and second
      NIR) fluorescence imaging of breast tumors at the cellular and whole-body level. 

PMID- 25564368
TI  - Nrf2-related gene expression and exposure to traffic-related air pollution in
      elderly subjects with cardiovascular disease: An exploratory panel study.
AB  - Gene expression changes are linked to air pollutant exposures in in vitro and
      animal experiments. However, limited data are available on how these outcomes
      relate to ambient air pollutant exposures in humans. We performed an exploratory
      analysis testing whether gene expression levels were associated with air
      pollution exposures in a Los Angeles area cohort of elderly subjects with
      coronary artery disease. Candidate genes (35) were selected from published
      studies of gene expression-pollutant associations. Expression levels were
      measured weekly in 43 subjects (<= 12 weeks) using quantitative PCR. Exposures
      included gaseous pollutants O3, nitrogen oxides (NOx), and CO; particulate matter
      (PM) pollutants elemental and black carbon (EC, BC); and size-fractionated PM
      mass. We measured organic compounds from PM filter extracts, including polycyclic
      aromatic hydrocarbons (PAHs), and determined the in vitro oxidative potential of
      particle extracts. Associations between exposures and gene expression levels were
      analyzed using mixed-effects regression models. We found positive associations of
      traffic-related pollutants (EC, BC, primary organic carbon, PM 0.25-2.5 PAH
      and/or PM 0.25 PAH, and NOx) with NFE2L2, Nrf2-mediated genes (HMOX1, NQO1, and
      SOD2), CYP1B1, IL1B, and SELP. Findings suggest that NFE2L2 gene expression links
      associations of traffic-related air pollution with phase I and II enzyme genes at
      the promoter transcription level.

PMID- 25564369
TI  - Assessing exposure to tobacco-specific carcinogen NNK using its urinary
      metabolite NNAL measured in US population: 2011-2012.
AB  - Carcinogenic tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)
      1-(3-pyridyl)-1-butanone (NNK) are found only in tobacco and derived products.
      Food and Drug Administration of the United States (US FDA) lists NNK as one of
      the 93 harmful and potentially harmful constituents (HPHCs) found in tobacco
      products and tobacco smoke. The aim of this study was to use the urinary
      concentration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a major
      metabolite of NNK, to quantitatively estimate exposure to NNK in the US general
      population. In 2011-2012, the Centers for Disease Control and Prevention's
      National Health and Nutrition Examination Survey (NHANES) collected urine and
      serum samples from a representative sample of US residents. We used a serum
      cotinine cutoff of 10 ng/ml with combination of questionnaire data to select non
      users from cigarette users and used self-reported data to determine different
      tobacco product user groups. We estimated the absorbed total daily dose of NNK
      using a probabilistic method based on a two-compartment model. The geometric mean
      (GM) for the daily dose of NNK among smokers aged 12-16 years was significantly
      higher than that for non-users at the same age stage exposed to second-hand smoke
      (SHS) (P<0.001). Among those exposed to SHS, the GM for daily dose of NNK in
      young children (6-11 years) was nearly three times of those for adults in the age
      range 21-59 years. Among cigarette users, non-Hispanic Whites had the highest NNK
      daily dose and Mexican Americans had the lowest levels. Exclusive snuff or
      chewing product users had significantly higher daily dose of NNK than did
      cigarette smokers. Our study found that the maximum daily dose of NNK for
      children aged from 6 to 11 years and that for a significant percentage of
      cigarette users, chewing product and snuff users were higher than an estimated
      provisional "reference" risk level. 

PMID- 25564370
TI  - Effect of study design on the reported effect of cardiac resynchronization
      therapy (CRT) on quantitative physiological measures: stratified meta-analysis in
      narrow-QRS heart failure and implications for planning future studies.
AB  - BACKGROUND: Biventricular pacing (CRT) shows clear benefits in heart failure with
      wide QRS, but results in narrow QRS have appeared conflicting. We tested the
      hypothesis that study design might have influenced findings. METHOD AND RESULTS:
      We identified all reports of CRT-P/D therapy in subjects with narrow QRS
      reporting effects on continuous physiological variables. Twelve studies (2074
      patients) met these criteria. Studies were stratified by presence of bias
      resistance steps: the presence of a randomized control arm over a single arm, and
      blinded outcome measurement. Change in each endpoint was quantified using a
      standardized effect size (Cohen's d). We conducted separate meta-analyses for
      each variable in turn, stratified by trial quality. In non-randomized, non
      blinded studies, the majority of variables (10 of 12, 83%) showed significant
      improvement, ranging from a standardized mean effect size of +1.57 (95%CI +0.43
      to +2.7) for ejection fraction to +2.87 (+1.78 to +3.95) for NYHA class. In the
      randomized, non-blinded study, only 3 out of 6 variables (50%) showed
      improvement. For the randomized blinded studies, 0 out of 9 variables (0%) showed
      benefit, ranging from -0.04 (-0.31 to +0.22) for ejection fraction to -0.1 (-0.73
      to +0.53) for 6-minute walk test. CONCLUSIONS: Differences in degrees of
      resistance to bias, rather than choice of endpoint, explain the variation between
      studies of CRT in narrow-QRS heart failure addressing physiological variables.
      When bias-resistance features are implemented, it becomes clear that these
      patients do not improve in any tested physiological variable. Guidance from
      studies without careful planning to resist bias may be far less useful than
      commonly perceived.

PMID- 25564371
TI  - Aldosterone promotes cardiac endothelial cell proliferation in vivo.
AB  - BACKGROUND: Experimentally, aldosterone in association with NaCl induces cardiac
      fibrosis, oxidative stress, and inflammation through mineralocorticoid receptor
      activation; however, the biological processes regulated by aldosterone alone in
      the heart remain to be identified. METHODS AND RESULTS: Mice were treated for 7
      days with aldosterone, and then cardiac transcriptome was analyzed. Aldosterone
      regulated 60 transcripts (51 upregulated and 9 downregulated) in the heart (fold
      change >=1.5, false discovery rate <0.01). To identify the biological processes
      modulated by aldosterone, a gene ontology analysis was performed. The majority of
      aldosterone-regulated genes were involved in cell division. The cardiac Ki-67
      index (an index of proliferation) of aldosterone-treated mice was higher than
      that of nontreated mice, confirming microarray predictions. Costaining of Ki-67
      with vinculin, CD68, alpha-smooth muscle actin, CD31, or caveolin 1 revealed that
      the cycling cells were essentially endothelial cells. Aldosterone-induced
      mineralocorticoid receptor-dependent proliferation was confirmed ex vivo in human
      endothelial cells. Moreover, pharmacological-specific blockade of
      mineralocorticoid receptor by eplerenone inhibited endothelial cell proliferation
      in a preclinical model of heart failure (transverse aortic constriction).
      CONCLUSIONS: Aldosterone modulates cardiac gene expression and induces the
      proliferation of cardiac endothelial cells in vivo.

PMID- 25564373
TI  - Cu-catalyzed cross-coupling reactions of epoxides with organoboron compounds.
AB  - A copper-catalyzed cross-coupling reaction of epoxides with arylboronates is
      described. This reaction is not limited to aromatic epoxides, because aliphatic
      epoxides are also suitable substrates. In addition, N-sulfonyl aziridines can be
      successfully converted into the products. This reaction provides convenient
      access to beta-phenethyl alcohols, which are valuable synthetic intermediates. 

PMID- 25564372
TI  - Lower mortality rate in elderly patients with community-onset pneumonia on
      treatment with aspirin.
AB  - BACKGROUND: Pneumonia is complicated by high rate of mortality and cardiovascular
      events (CVEs). The potential benefit of aspirin, which lowers platelet
      aggregation by inhibition of thromboxane A2 production, is still unclear. The aim
      of the study was to assess the impact of aspirin on mortality in patients with
      pneumonia. METHODS AND RESULTS: Consecutive patients admitted to the University
      Hospital Policlinico Umberto I (Rome, Italy) with community-onset pneumonia were
      recruited and prospectively followed up until discharge or death. The primary end
      point was the occurrence of death up to 30 days after admission; the secondary
      end point was the intrahospital incidence of nonfatal myocardial infarction and
      ischemic stroke. One thousand and five patients (age, 74.7+/-15.1 years) were
      included in the study: 390 were receiving aspirin (100 mg/day) at the time of
      hospitalization, whereas 615 patients were aspirin free. During the follow-up,
      16.2% of patients died; among these, 19 (4.9%) were aspirin users and 144 (23.4%;
      P<0.001) were aspirin nonusers. Overall, nonfatal CVEs occurred in 7% of
      patients, 8.3% in nonaspirin users, and 4.9% in aspirin users (odds ratio, 1.77;
      95% confidence interval, 1.03 to 3.04; P=0.040). The Cox regression analysis
      showed that pneumonia severity index (PSI), severe sepsis, pleural effusion, and
      PaO(2)/FiO(2) ratio <300 negatively influenced survival, whereas aspirin therapy
      was associated with improved survival. Compared to patients receiving aspirin,
      the propensity score adjusted analysis confirmed that patients not taking aspirin
      had a hazard ratio of 2.07 (1.08 to 3.98; P=0.029) for total mortality.
      CONCLUSIONS: This study shows that chronic aspirin use is associated with lower
      mortality rate within 30 days after hospital admission in a large cohort of
      patients with pneumonia.

PMID- 25564374
TI  - Complete sequence-based screening of TPMT variants in the Korean population.
AB  - Thiopurine S-methyltransferase (TPMT) is a cytoplasmic enzyme involved in the
      metabolism of thiopurine drugs and its activity is largely influenced by
      polymorphisms of the TPMT gene. To date, more than 35 TPMT variants are known to
      be associated with reduced enzyme activity, but most studies on the TPMT genotype
      have included only common nonfunctional variants, such as TPMT*2 and TPMT*3. In
      this study, we carried out a complete sequencing analysis to screen all TPMT
      variants in Korean patients. A total of 900 Korean patients were genotyped for
      TPMT and 30 patients (3.3%) had the known TPMT variant alleles. TPMT*3C was found
      in 25 patients (2.8%): 24 patients with TPMT*1/*3 and one with TPMT*3/*3. Rare
      TPMT variants including TPMT*6, TPMT*16, and TPMT*32 were detected in five
      patients (0.6%) and a novel variant, TPMT*38 (c.514T>C, p.S172P), was identified
      in two patients. This is the first complete sequence-based screening study
      evaluating all TPMT variants in Asian populations. 

PMID- 25564375
TI  - Peripheral blood IRF1 expression as a marker for glucocorticoid sensitivity.
AB  - OBJECTIVE: Despite of the common usage of glucocorticoids (GCs), a significant
      portion of asthma patients exhibit GC insensitivity. This could be mediated by
      diverse mechanisms, including genomics. Recent work has suggested that measuring
      changes in gene expression may provide more predictive information about GC
      insensitivity than baseline gene expression alone, and that expression changes in
      peripheral blood may be reflective of those in the airway. METHODS: We performed
      in silico discovery using gene expression omnibus (GEO) data that evaluated GC
      effect on gene expression in multiple tissue types. Subsequently, candidate genes
      whose expression levels are affected by GC were examined in cell lines and in
      primary cells derived from human airway and blood. RESULTS: Through gene
      expression omnibus analysis, we identified interferon regulator factor 1 (IRF1),
      whose expression is affected by GC treatment in airway smooth muscle cells,
      normal human bronchial epithelial (NHBE) cells, and lymphoblastoid cell lines
      (LCLs). Significant IRF1 downregulation post GC exposure was confirmed in two
      cultured airway epithelial cell lines and primary NHBE cells (P<0.05). We
      observed large interindividual variation in GC-induced IRF1 expression changes
      among primary NHBE cells tested. Significant downregulation of IRF1 was also
      observed in six randomly selected LCLs (P<0.05), with variable degrees of
      downregulation among different samples. In peripheral blood mononuclear cells
      obtained from healthy volunteers, variable downregulation of IRF1 by GC was also
      shown. NFKB1, a gene whose expression is known to be downregulated by GC and the
      degree of downregulation of which is reflective of GC response, was used as a
      control in our study. IRF1 shows more consistent downregulation across tissue
      types when compared with NFKB1. CONCLUSION: Our results suggest that GC-induced
      IRF1 gene expression changes in peripheral blood could be used as a marker to
      reflect GC response in the airway.

PMID- 25564376
TI  - Novel agonists of benzodiazepine receptors: design, synthesis, binding assay and
      pharmacological evaluation of 1,2,4-triazolo[1,5-a]pyrimidinone and 3-amino-1,2,4
      triazole derivatives.
AB  - Agonists of benzodiazepine (BZD) binding site in GABA receptors are widely used
      in clinical practice. In spite of their benefits they have several side effects,
      so synthesis of new agonists of these receptors to get more specific effect and
      better profile of adverse drug reactions is still continued. Novel BZD agonists
      were designed based on the pharmacophore/receptor model of BZD binding site of
      GABAA receptor. Energy minima conformers of the designed compounds and estazolam,
      a known BZD receptor agonist, were well superimposed in conformational analysis.
      Docking studies revealed that the carbonyl group of the compound 4c, 3-(2
      chlorobenzyl)-5-methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one, was
      near the nitrogen moiety of triazole ring of estazolam providing the hydrogen
      bond acceptor in proper direction in the BDZ-binding site of GABAA receptor model
      (alpha1beta2Upsilon2). The designed compounds were synthesized and their in vitro
      affinity for the central BZD receptor was determined. Most of the novel compounds
      had better affinity for the BZD site of action on GABAA receptor complex than
      diazepam. Finally, the novel compound 4c with the best affinity in radioligand
      receptor binding assay (Ki=0.42 nM and IC50=0.68 nM) was selected as candidate
      for in vivo evaluation. This compound showed significant hypnotic activity and
      weak anticonvulsant effect with no impairment on learning and memory performance
      in mouse. The pharmacological effects of the compound 4c were antagonized by
      flumazenil, a BZD antagonist, which confirms the involvement of BZD receptors in
      the biological effects of the novel ligand.

PMID- 25564377
TI  - Natural antitubulin agents: importance of 3,4,5-trimethoxyphenyl fragment.
AB  - Microtubules are polar cytoskeletal filaments assembled from head-to-tail and
      comprised of lateral associations of alpha/beta-tubulin heterodimers that play
      key role in various cellular processes. Because of their vital role in mitosis
      and various other cellular processes, microtubules have been attractive targets
      for several disease conditions and especially for cancer. Antitubulin is the most
      successful class of antimitotic agents in cancer chemotherapeutics. The target
      recognition of antimitotic agents as a ligand is not much explored so far.
      However, 3,4,5-trimethoxyphenyl fragment has been much highlighted and discussed
      in such type of interactions. In this review, some of the most important
      naturally occurring antimitotic agents and their interactions with microtubules
      are discussed with a special emphasis on the role of 3,4,5-trimethoxyphenyl unit.
      At last, some emerging naturally occurring antimitotic agents have also been
      tabulated. 

PMID- 25564378
TI  - Fluoro-substituted phenylazocarboxamides: Dopaminergic behavior and N-arylating
      properties for irreversible binding.
AB  - Phenylazocarboxamides can serve as bioisosteres for cinnamides, which are widely
      occurring substructures in medicinal chemistry. Starting from our lead compound
      2, the introduction of additional fluoro substituents and the exchange of the
      methoxyphenylpiperazine head group by an aminoindane moiety was investigated
      resulting in dopamine D3 receptor antagonists and agonists with Ki values in the
      sub- and low-nanomolar range. As a potentially irreversible ligand, the 3,4,5
      trifluoro-substituted phenylazocarboxamide 7 was investigated for its N-arylating
      properties by incubation with the protected lysine analog 18 and with the L89K
      mutant of the dopamine D3 receptor. Whereas covalent bond formation with the
      lysine unit in TM2 of D3 could not be detected, substantial N-arylation of the
      side chain of the model compound 18 has been observed. 

PMID- 25564381
TI  - Artificial tektites: an experimental technique for capturing the shapes of
      spinning drops.
AB  - Determining the shapes of a rotating liquid droplet bound by surface tension is
      an archetypal problem in the study of the equilibrium shapes of a spinning and
      charged droplet, a problem that unites models of the stability of the atomic
      nucleus with the shapes of astronomical-scale, gravitationally-bound masses. The
      shapes of highly deformed droplets and their stability must be calculated
      numerically. Although the accuracy of such models has increased with the use of
      progressively more sophisticated computational techniques and increases in
      computing power, direct experimental verification is still lacking. Here we
      present an experimental technique for making wax models of these shapes using
      diamagnetic levitation. The wax models resemble splash-form tektites, glassy
      stones formed from molten rock ejected from asteroid impacts. Many tektites have
      elongated or 'dumb-bell' shapes due to their rotation mid-flight before
      solidification, just as we observe here. Measurements of the dimensions of our
      wax 'artificial tektites' show good agreement with equilibrium shapes calculated
      by our numerical model, and with previous models. These wax models provide the
      first direct experimental validation for numerical models of the equilibrium
      shapes of spinning droplets, of importance to fundamental physics and also to
      studies of tektite formation. 

PMID- 25564380
TI  - Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease:
      inhibition kinetics and docking studies.
AB  - NS2B-NS3 is a serine protease of the Dengue virus considered a key target in the
      search for new antiviral drugs. In this study flavonoids were found to be
      inhibitors of NS2B-NS3 proteases of the Dengue virus serotypes 2 and 3 with IC50
      values ranging from 15 to 44 MUM. Agathisflavone (1) and myricetin (4) turned out
      to be noncompetitive inhibitors of dengue virus serotype 2 NS2B-NS3 protease with
      Ki values of 11 and 4.7 MUM, respectively. Docking studies propose a binding mode
      of the flavonoids in a specific allosteric binding site of the enzyme. Analysis
      of biomolecular interactions of quercetin (5) with NT647-NHS-labeled Dengue virus
      serotype 3 NS2B-NS3 protease by microscale thermophoresis experiments, yielded a
      dissociation constant KD of 20 MUM. Our results help to understand the mechanism
      of inhibition of the Dengue virus serine protease by flavonoids, which is
      essential for the development of improved inhibitors.

PMID- 25564382
TI  - An improved model for predicting electrical conductance in nanochannels.
AB  - Nanochannel conductance measurements are commonly performed to characterize
      nanofluidic devices Theoretical analysis and experimental investigations imply
      that the nanochannel conductance does not follow the macro-scale models. It is
      generally accepted that the conductance of nanochannels deviates from the bulk
      and trend to a constant value at low concentrations. In this work, we present an
      improved model for the nanochannel conductance that takes into account the
      surface chemistry of the nanochannel wall. It figured out that the nanochannel
      conductance is no longer constant at low concentrations. The model predictions
      were compared with the experimental measurements and showed a very good agreement
      between the model and the experiments. 

PMID- 25564379
TI  - Identification of the dioxygenase-generated intermediate formed during
      biosynthesis of the dihydropyrrole moiety common to anthramycin and sibiromycin.
AB  - A description of pyrrolo[1,4]benzodiazepine (PBD) biosynthesis is a prerequisite
      for engineering production of analogs with enhanced antitumor activity. Predicted
      dioxygenases Orf12 and SibV associated with dihydropyrrole biosynthesis in PBDs
      anthramycin and sibiromycin, respectively, were expressed and purified for
      activity studies. UV-visible spectroscopy revealed that these enzymes catalyze
      the regiospecific 2,3-extradiol dioxygenation of l-3,4-dihydroxyphenylalanine (l
      DOPA) to form l-2,3-secodopa (lambdamax=368 nm). (1)H NMR spectroscopy indicates
      that l-2,3-secodopa cyclizes into the alpha-keto acid tautomer of l-4-(2-oxo-3
      butenoic-acid)-4,5-dihydropyrrole-2-carboxylic acid (lambdamax=414 nm). Thus, the
      dioxygenases are key for establishing the scaffold of the dihydropyrrole moiety.
      Kinetic studies suggest the dioxygenase product is relatively labile and is
      likely consumed rapidly by subsequent biosynthetic steps. The enzymatic product
      and dimeric state of these dioxygenases are conserved in dioxygenases involved in
      dihydropyrrole and pyrrolidine biosynthesis within both PBD and non-PBD pathways.

PMID- 25564383
TI  - Peri- and postinterventional antithrombotic therapy in TAVI. Do we need
      antiplatelet therapy?
AB  - Interventional treatment of aortic valve stenosis by transcatheter aortic valve
      replacement (TAVR) has become routine practice in elderly and high risk patients
      in recent years. Similar to other vascular interventional or surgical procedures
      TAVR carries thrombotic risks such as stroke, myocardial infarction or systemic
      embolism as well as peri-procedural bleeding risks. These risks comprise the
      access site, the type of prosthesis, and the individual risk profile of the
      patient. Not only during the peri-procedural period but also during longterm
      follow-up the current target population for TAVR procedures carries a high risk
      for thrombotic events in particular if atrial fibrillation is present. On the
      other hand side the bleeding risk is also increased in these patients. Thus, to
      provide the optimal strategy of antithrombotic therapy during and after TAVR
      remains a clinical challenge. 

PMID- 25564384
TI  - Impact of early life stress on psychiatric disorders: searching new biomarkers
      and innovative pharmacological targets.

PMID- 25564386
TI  - The long-term impact of early adversities on psychiatric disorders: focus on
      neuronal plasticity.
AB  - The impact of early physical and social environments on life-long pathological
      phenotypes is well known and there is now compelling evidence that stressful
      experiences during gestation or early in life can lead to enhanced susceptibility
      to mental illness. Here, we discuss the data from preclinical studies aimed at
      investigating the molecular consequences of the exposure to stressful events
      during prenatal or early postnatal life that might contribute to later
      psychopathology. Particularly, we will discuss the existence of age windows of
      vulnerability to environmental conditions during brain maturation using as
      examples several studies performed with different animal models. Specifically,
      major deviations from normative neurobehavioural trajectories have been reported
      in animal models obtained following exposure to severe stress (maternal
      separation) ea rly in infancy or with rodent models of difficult and/or stressful
      pregnancies, including obstetric complications (e.g. prenatal restrain stress)
      and gestational exposure to infection (e.g prenatal immune challenge). These
      models have been associated with profound long-lasting deficits in the
      offspring's emotional and social behaviour, and with molecular changes associated
      with neuroplasticity. 

PMID- 25564385
TI  - Impact of early life stress on the pathogenesis of mental disorders: relation to
      brain oxidative stress.
AB  - Stress is an inevitable part of human life and it is experienced even before
      birth. Stress to some extent could be considered normal and even necessary for
      the survival and the regular psychological development during childhood or
      adolescence. However, exposure to prolonged stress could become harmful and
      strongly impact mental health increasing the risk of developing psychiatric
      disorders. Recent studies have attempted to clarify how the human central nervous
      system (CNS) reacts to early life stress, focusing mainly on neurobiological
      modifications. Oxidative stress, defined as a disequilibrium between the oxidant
      generation and the antioxidant response, has been recently described as a
      candidate for most of the observed modifications. In this review, we will discuss
      how prolonged stressful events during childhood or adolescence (such as early
      maternal separation, parental divorce, physical violence, sexual or psychological
      abuses, or exposure to war events) can lead to increased oxidative stress in the
      CNS and enhance the risk to develop psychiatric diseases such as anxiety,
      depression, drug abuse or psychosis. Defining the sources of oxidative stress
      following exposure to early life stress might open new beneficial insights in
      therapeutic approaches to these mental disorders. 

PMID- 25564387
TI  - Early life stress in depressive patients: role of glucocorticoid and
      mineralocorticoid receptors and of hypothalamic-pituitary-adrenal axis activity.
AB  - Depression is a chronic, recurrent and long-term disorder characterized by high
      rates of impairment and several comorbidities. Early life stress (ELS) is
      associated with the increased risk for developing depression in adulthood,
      influences its clinical course and predicts a poorer treatment outcome. Stressful
      life events play an important role in the pathogenesis of depression, being well
      established as acute triggers of psychiatric illness. The vulnerability for
      developing depression is associated to changes in neurobiological systems related
      to stress regulation. The hypothalamic-pituitaryadrenal (HPA) axis responds to
      external and internal stimuli. Reported results indicate that stress in early
      phases of development can induce persistent changes in the response of the HPA
      axis to stress in adulthood, leading to a raised susceptibility to depression.
      These abnormalities appear to be related to the HPA axis deregulation in
      depression, partially due to an imbalance between glucocorticoid receptors (GR)
      and mineral ocorticoid receptors (MR). While most studies have consistently
      demonstrated that GR function is impaired in major depression (reduced GR
      mediated feedback in HPA axis), data about the MR role in depression are still
      limited and contr oversial. Thus, in this review article we summarize the main
      reported findings about the consequences of ELS in HPA axis functioning and in
      the responsivity of MR/GR receptors in depression. 

PMID- 25564389
TI  - Drugs of abuse in pregnancy, poor neonatal development, and future
      neurodegeneration. Is oxidative stress the culprit?
AB  - The abuse of licit and illicit drugs is a worldwide issue that is a cause for
      concern in pregnant women. It may lead to complications in pregnancy that may
      affect the mother, fetus, and /or neonate. The effects of any substance on the
      developing embryo and fetus are dependent upon dosing, timing, duration of drug
      exposure, and the extent of drug distribution. Teratogenic effects have been
      described when exposure takes place during the embryonic stage; however drugs
      have subtle effects, including abnormal growth and/or maturation, alterations in
      neurotransmitters and their receptors, and brain organization. The mechanisms by
      which intrauterine exposure to many substances may result in neuronal injury have
      not been completely elucidated. Oxidative stress and epigenetic changes have been
      recently implicated in the pathogenesis of long - term adverse health sequelae,
      and neuro-developmental impairment in the offspring of addicted mothers.
      Transgenerational epigenetics may also explain the alarming datum that
      developmental abnormalities, impairment in learning and memory, and attention
      deficit can occur even in the absence of direct fetal exposure, when drugs are
      consumed prior to conception. There is a growing body of evidence demonstrating a
      link between redox state unbalance, epigenetic markers, developmental anomalies,
      and neurodegeneration. The reviewed literature data uphold redox homeostasis
      disruption as an important factor in the pathogenesis of drug of abuse- induced
      neurodegeneration, and highlight the potential for new therapies that could
      prevent neurodegeneration through antioxidant and epigenetic modulatory
      mechanisms. This therefore reveals important targets for novel neuroprotective
      strategies. 

PMID- 25564388
TI  - Childhood maltreatment and stress-related psychopathology: the epigenetic memory
      hypothesis.
AB  - Childhood maltreatment (CM) is all too frequent among western societies, with an
      estimated prevalence of 10 to 15%. CM associates with increased risk of several
      psychiatric disorders, and therefore represents a worrying public and
      socioeconomic burden. While associated clinical outcomes are well characterized,
      determining by which mechanisms early-life adverse experiences affect mental
      health over the lifespan is a major challenge. Epigenetic mechanisms, in
      particular DNA methylation, represent a form of molecular memory that may modify
      brain function over extended periods of time, as well as serve as a bio-marker of
      behavioral phenotypes associated with CM. Here, we review human studies
      suggesting that DNA methylation is a crucial substrate mediating neurobiological
      consequences of CM throughout life, thereby potentiating maladaptive behavioral
      patterns and psychopathological risk. 

PMID- 25564390
TI  - Early life and oxidative stress in psychiatric disorders: what can we learn from
      animal models?
AB  - Schizophrenia is a complex pathology characterized by the occurrence of a variety
      of symptoms classified as positive, negative and cognitive. Although the exact
      etiopathogenesis of this disorder has not been unraveled yet, many theories have
      been endorsed during the last years. Among these, the neurochemical theories have
      been the most suited, considering the dopaminergic and glutamatergic dysfunctions
      to be mainly responsible for psychotic symptoms. However, the lack of efficacy of
      the available drugs, namely antipsychotics, toward negative and cognitive
      symptoms led to hypothesize alternative approaches. In this regard, the
      neurodevelopmental theory of schizophrenia has emerged, proposing the association
      between the occurrence of environmental risk factors in early-life and the
      development of psychosis in late-life. In particular, exposure to early life
      stressing situations, such as pre- and peri-natal stress, has been suggested as a
      risk factor to d evelop psychopathologies in adulthood in people genetically
      predisposed. A crucial support in favor of this hypothesis came from
      neurodevelopmental animal models of schizophrenia, such as maternal malnutrition,
      maternal deprivation, maternal infections as well as post-weaning social
      isolation rearing. Moreover, data from these models, corroborated by clinical
      findings, indicate that oxidative and nitrosative stress play a crucial role in
      the etiopathogenesis of psychiatric disorders. In the present work, we reviewed
      the recent progress in literature regarding data available from animal models
      linking oxidative and nitrosative stress to psychiatric disorders in order to
      evaluate novel biomarkers of pathology as well as novel therapeutical targets. 

PMID- 25564391
TI  - Cerebral white matter injuries following a hypoxic/ischemic insult during the
      perinatal period: pathophysiology, prognostic factors, and future strategy of
      treatment approach. A minireview.
AB  - Recent advances in medical care have significantly improved the survival rate of
      neonates who suffer a hypoxic/ ischemic event, before, during, or after birth.
      These infants are extremely vulnerable to brain injury and are at high risk of
      developing motor and cognitive abnormalities later on in life. The regional
      distribution of perinatal brain injury varies, and depends primarily on; the
      severity, pattern and type of insult, the metabolic status, and on the
      gestational age. The principal neuropathological substrate that is affected in
      the premature infant is cerebral white matter. The aim of this article is to re
      examine the current knowledge on the ischemic pathophysiology of all cellular
      components that comprise the white matter, pred ict the consequences of the long
      term neurological outcome, and analyze possible therapeutic strategies. Although
      oligodendrocytes have long been regarded as the hallmark of perinatal white
      matter injury, axons, astrocytes and microglia, all contribute to the complex
      pattern of brain injury that occurs in this cohort of individuals. It is hoped
      that a better understanding of the pathophysiology of white matter injury and its
      underlying prognostic factors, may lead to the development of new therapeutic
      strategies for such a complex and debilitating condition. 

PMID- 25564392
TI  - Early-life stress and psychiatric disorders: epidemiology, neurobiology and
      innovative pharmacological targets.
AB  - The modern concept of stress is based on responses to events or factors
      ("stressors") experienced as aversive, threatening or excessive for maintaining
      physiological equilibrium of an organism. Prolonged exposure to stressors,
      particularly during early life, is strongly associated with later psychiatric
      disorders. Underlying mechanistic connections between stress responses and
      development of psychiatric illnesses remain uncertain and typically appear to be
      nonspecific. Relevant candidate mechanisms are likely to include the hypothalamic
      pituitary-adrenal (HPA) axis, marked by sustained excessive release of cortisol
      from the adrenal cortex. In turn, this process is influenced by and alters
      various central neurotransmitter and other molecular signaling systems that
      include glutamate, dopamine, serotonin, and neurotrophic peptides. Additional
      manifestations of stress include altered neurogenesis and neuroplasticity, as
      well as oxidative neuron-damaging effects. The complex molecular systems involved
      in these processes present many opportunities for innovative pharmacological
      interventions that may have preventive or therapeutic benefits regarding mental
      illnesses arising from stress.

PMID- 25564393
TI  - Stimulatory effects of blue light on the growth, monascin and ankaflavin
      production in Monascus.
AB  - Light is an important signal for fungi. We analyzed the influence of blue light
      of various intensities and illumination times on growth, monascin (MS) and
      ankaflavin (AK) biosyntheses in Monascus strain M9. Blue light changed the color
      of colonies. The colonies grown in the dark were orange, but turned pale when
      exposed to continuous blue light. MS production increased by 12.5, 27, and 14.5 %
      under blue light of 100 lux for 15 min/day, 100 lux for 30 min/day, and 200 lux
      for 15 min/day, respectively, compared to growth in the dark. AK production
      increased by 14.4, 22, and 13 % under the same condition. MS and AK production
      decreased when exposed to blue light of 300 and 450 lux. The expression of
      pigment biosynthetic genes were analyzed by real-time quantitative PCR and
      correlated with phenotypic production of MS and AK.

PMID- 25564394
TI  - Flow-through polymerase chain reaction inside a seamless 3D helical microreactor
      fabricated utilizing a silicone tube and a paraffin mold.
AB  - We introduce a new strategy for fabricating a seamless three-dimensional (3D)
      helical microreactor utilizing a silicone tube and a paraffin mold. With this
      method, various shapes and sizes of 3D helical microreactors were fabricated, and
      a complicated and laborious photolithographic process, or 3D printing, was
      eliminated. With dramatically enhanced portability at a significantly reduced
      fabrication cost, such a device can be considered to be the simplest
      microreactor, developed to date, for performing the flow-through polymerase chain
      reaction (PCR). 

PMID- 25564395
TI  - Reliability and feasibility of longitudinal AFI global and segmental strain
      compared with 2D left ventricular volumes and ejection fraction: intra- and inter
      operator, test-retest, and inter-cycle reproducibility.
AB  - AIMS: Echocardiographic evaluation of 2D longitudinal peak systolic strain (LPSS)
      can detect initial impairment of left ventricular (LV) function in heart disease.
      Global LPSS (GLPSS) variability has been assessed in small groups and segmental
      LPSS has not been determined. We compared variability of GLPSS and segmental LPSS
      with that of 2D LV volumes and ejection fraction (EF) in patients with and
      without heart diseases. METHODS AND RESULTS: 2D speckle tracking analysis was
      performed on LV apical views using automated function imaging (AFI) software (GE
      Healthcare). Intra-operator, inter-cycle, and test-retest variability (bias and
      CR, coefficient of reproducibility; MPE, mean percent error; CV, coefficient of
      variation) was assessed for GLPSS, 18 segments of LPSS, and LV volumes and EF in
      40 patients (720 segments), and inter-operator variability in 250 patients (4500
      segments). Feasibility of segmental tracking was 93.1%. Variability of GLPSS
      increased from a minimum intra-operator CV = -2.6% to a maximum test-retest CV = 
      5.4% and was lower than that assessed for volumes and EF. Segmental intra
      operator LPSS CV ranged from -5.6 to -14.7%, and test-retest from -8 to -22%, and
      was at worst similar to variability of end-systolic volume. In the 8.3% of
      segments with the highest variability, this was related to suboptimal imaging,
      minor changes in scan angulation, and insufficient ROI width. CONCLUSION:
      Overall, reproducibility of GLPSS is excellent and superior to that of 2D EF,
      whereas segmental LPSS reproducibility is good and similar to that of LV volumes.
      Both are suitable for diagnosis and follow-up of LV global and regional systolic
      function.

PMID- 25564397
TI  - Increased expression of 17-beta-hydroxysteroid dehydrogenase type 1 in non-small
      cell lung cancer.
AB  - OBJECTIVES: Recent studies indicated that estrogens may influence the development
      of non-small cell lung cancer (NSCLC). The 17-beta-hydroxysteroid dehydrogenase
      type 1 (HSD17B1) catalyzes the reduction of estrone (E1) to the highly potent E2.
      Although the significance of aromatase in an intratumoral E2 production in NSCLC
      is well established, the role of HSD17B1 remains largely unknown. Therefore, we
      investigated the expression of HSD17B1 in lung cancerous and corresponding
      histopathologically unchanged tissues from NSCLC patients and the association
      between HSD17B1 expression and clinicopathological features. Than, we examined
      the biological significance of HSD17B1 in NSCLC cells in vitro. We tested the
      impact of 5-Aza-2'-deoxycytidine (5-dAzaC) on HSD17B1 expression and activity.
      MATERIALS AND METHODS: We used Real Time quantitative PCR (RT-qPCR), Western
      blotting and immunohistochemistry to evaluate HSD17B1 expression in tissues
      obtained from 48 patients with NSCLC. The methylation status of the promoter
      region of HSD17B1 in A549 and Calu-1 cells was evaluated by bisulfite sequencing.
      We investigated the effect of 5-dAzaC on HSD17B1 transcript levels (by RT-qPCR)
      and on HSD17B1 enzyme activity by measuring the conversion of E1 to E2. The
      xCELLigence System was used for monitoring of cell proliferation. RESULTS: We
      found a substantial increase of HSD17B1 mRNA and protein amount in NSCLC tissues
      compared with histopathologically unchanged tissues in the group of male
      patients. An overexpression of HSD17B1 was associated with squamous cell
      carcinoma and with lung cancer stage 3A. We showed that 5-dAzaC induces DNA
      demethylation of HSD17B1 promoter, leading to increased HSD17B1 mRNA levels and
      protein activity in NSCLC cells. It resulted in enhanced E2 production in both
      cell lines and supported the proliferation of Calu-1 cells but not A549 cells.
      CONCLUSION: Increased expression of HSD17B1 in NSCLC may contribute to an
      elevated intratissue level of E2 and consequently may support the development and
      spread of cancer.

PMID- 25564396
TI  - The utility of handheld echocardiography for early rheumatic heart disease
      diagnosis: a field study.
AB  - AIMS: The World Heart Federation (WHF) guidelines for rheumatic heart disease
      (RHD) are designed for a standard portable echocardiography (STAND) machine. A
      recent study in a tertiary care centre demonstrated that they also had good
      sensitivity and specificity when modified for use with handheld echocardiography
      (HAND). Our study aimed to evaluate the performance of HAND for early RHD
      diagnosis in the setting of a large-scale field screening. METHODS AND RESULTS:
      STAND was performed in 4773 children in Gulu, Uganda, with 10% randomly assigned
      to also undergo HAND. Additionally, any child with mitral or aortic regurgitation
      also underwent HAND. Studies were performed by experienced echocardiographers and
      blindly reviewed by cardiologists using 2012 WHF criteria, which were modified
      slightly for HAND--due to the lack of spectral Doppler capability. Paired
      echocardiograms were performed in 1420 children (mean age 10.8 and 53% female),
      resulting in 1234 children who were normal, 133 who met criteria for borderline
      RHD, 47 who met criteria for definite RHD, and 6 who had other diagnoses. HAND
      had good sensitivity and specificity for RHD detection (78.9 and 87.2%,
      respectively), but was most sensitive for definite RHD (97.9%). Inter- and intra
      reviewer agreement ranged between 66-83 and 71.4-94.1%, respectively.
      CONCLUSIONS: HAND has good sensitivity and specificity for diagnosis of early
      RHD, performing best for definite RHD. Protocols for RHD detection utilizing HAND
      will need to include confirmation by STAND to avoid over-diagnosis. Strategies
      that evaluate simplified screening protocols and training of non-physicians hold
      promise for more wide spread deployment of HAND-based protocols.

PMID- 25564398
TI  - Longitudinal analysis of 2293 NSCLC patients: a comprehensive study from the
      TYROL registry.
AB  - INTRODUCTION: The aim of this study was to describe a large consecutive cohort of
      non-small cell lung cancer (NSCLC) patients treated in daily routine within the
      last 25 years. An extensive list of general baseline characteristics
      (comorbidities, laboratory values, symptoms, performance state), NSCLC related
      factors (stage, histology), treatment related parameters (approach, applied
      therapies) and outcome (PFS, RFS, OS, perspective of decades) were analyzed in
      detail. PATIENTS AND METHODS: Medical files of 2293 consecutive NSCLC patients
      diagnosed between 1989 and 2009 at the Medical University of Innsbruck and
      affiliated hospitals were retrospectively analyzed. Patients were documented
      within our institution's comprehensive lung cancer project "Twenty-Year
      Retrospective of Lung Cancer (TYROL study)". RESULTS: Mean age at diagnosis was
      64.1 years and 1611 patients (70.3%) were male. Most patients were diagnosed in
      stage IV (37.9%). The most frequent comorbidities present at diagnosis were
      cardiovascular disease (62.1%) and COPD (62.0%). The most common symptoms at
      diagnosis were coughing (54.7%) and dyspnea (45.3%). Of all 2293 patients 1981
      (86.4%) received adequate antineoplastic treatment. In total 874 patients were
      radically operated, 119 received radiotherapy/radio-chemotherapy and the majority
      of patients (n=1278) were treated in palliative intent. A 2nd, 3rd, 4th and 5th
      line palliative therapy was administered to 612, 278, 102, and 36 patients.
      Median OS, RFS and PFS were 16.4 months, 86.4 months and 5.1 months,
      respectively. A multitude of factors was associated with all three outcome
      variables. Of note, outcome has improved stepwise in the recent decade based on
      increased response rates leading to prolonged OS. CONCLUSION: This work
      incorporates most clinical aspects relevant in the treatment of NSCLC and beyond.
      Therefore, this comprehensive analysis provides a definite benchmark for
      prognostication and epidemiology of NSCLC in a Western European society.

PMID- 25564399
TI  - How I treat juvenile myelomonocytic leukemia.
AB  - Juvenile myelomonocytic leukemia (JMML) is a unique, aggressive hematopoietic
      disorder of infancy/early childhood caused by excessive proliferation of cells of
      monocytic and granulocytic lineages. Approximately 90% of patients carry either
      somatic or germline mutations of PTPN-11, K-RAS, N-RAS, CBL, or NF1 in their
      leukemic cells. These genetic aberrations are largely mutually exclusive and
      activate the Ras/mitogen-activated protein kinase pathway. Allogeneic
      hematopoietic stem cell transplantation (HSCT) remains the therapy of choice for
      most patients with JMML, curing more than 50% of affected children. We recommend
      that this option be promptly offered to any child with PTPN-11-, K-RAS-, or NF1
      mutated JMML and to the majority of those with N-RAS mutations. Because children
      with CBL mutations and few of those with N-RAS mutations may have spontaneous
      resolution of hematologic abnormalities, the decision to proceed to
      transplantation in these patients must be weighed carefully. Disease recurrence
      remains the main cause of treatment failure after HSCT. A second allograft is
      recommended if overt JMML relapse occurs after transplantation. Recently,
      azacytidine, a hypomethylating agent, was reported to induce
      hematologic/molecular remissions in some children with JMML, and its role in both
      reducing leukemia burden before HSCT and in nontransplant settings requires
      further studies. 

PMID- 25564400
TI  - The role of the ADAMTS13 cysteine-rich domain in VWF binding and proteolysis.
AB  - ADAMTS13 proteolytically regulates the platelet-tethering function of von
      Willebrand factor (VWF). ADAMTS13 function is dependent upon multiple exosites
      that specifically bind the unraveled VWF A2 domain and enable proteolysis. We
      carried out a comprehensive functional analysis of the ADAMTS13 cysteine-rich
      (Cys-rich) domain using engineered glycans, sequence swaps, and single point
      mutations in this domain. Mutagenesis of Cys-rich domain-charged residues had no
      major effect on ADAMTS13 function, and 5 out of 6 engineered glycans on the Cys
      rich domain also had no effect on ADAMTS13 function. However, a glycan attached
      at position 476 appreciably reduced both VWF binding and proteolysis.
      Substitution of Cys-rich sequences for the corresponding regions in ADAMTS1
      identified a hydrophobic pocket involving residues Gly471-Val474 as being of
      critical importance for both VWF binding and proteolysis. Substitution of
      hydrophobic VWF A2 domain residues to serine in a region (residues 1642-1659)
      previously postulated to interact with the Cys-rich domain revealed the
      functional importance of VWF residues Ile1642, Trp1644, Ile1649, Leu1650, and
      Ile1651. Furthermore, the functional deficit of the ADAMTS13 Cys-rich Gly471
      Val474 variant was dependent on these same hydrophobic VWF residues, suggesting
      that these regions form complementary binding sites that directly interact to
      enhance the efficiency of the proteolytic reaction. 

PMID- 25564402
TI  - Manifestations and clinical impact of pediatric inherited thrombophilia.
AB  - The etiology of pediatric venous thromboembolic disease (VTE) is multifactorial,
      and in most children, 1 or more clinical risk factors are present. In addition,
      inherited thrombophilic disorders contribute to the development of pediatric VTE.
      In this review, the role of inherited thrombophilic disorders in the development
      of pediatric VTE, as well as the benefits and limitations of thrombophilia
      testing, will be discussed. 

PMID- 25564401
TI  - Hemophagocytic lymphohistiocytosis caused by dominant-negative mutations in
      STXBP2 that inhibit SNARE-mediated membrane fusion.
AB  - Familial hemophagocytic lymphohistiocytosis (F-HLH) and Griscelli syndrome type 2
      (GS) are life-threatening immunodeficiencies characterized by impaired cytotoxic
      T lymphocyte (CTL) and natural killer (NK) cell lytic activity. In the majority
      of cases, these disorders are caused by biallelic inactivating germline mutations
      in genes such as RAB27A (GS) and PRF1, UNC13D, STX11, and STXBP2 (F-HLH).
      Although monoallelic (ie, heterozygous) mutations have been identified in certain
      patients, the clinical significance and molecular mechanisms by which these
      mutations influence CTL and NK cell function remain poorly understood. Here, we
      characterize 2 novel monoallelic hemophagocytic lymphohistiocytosis (HLH)
      associated mutations affecting codon 65 of STXPB2, the gene encoding Munc18-2, a
      member of the SEC/MUNC18 family. Unlike previously described Munc18-2 mutants,
      Munc18-2(R65Q) and Munc18-2(R65W) retain the ability to interact with and
      stabilize syntaxin 11. However, presence of Munc18-2(R65Q/W) in patient-derived
      lymphocytes and forced expression in control CTLs and NK cells diminishes
      degranulation and cytotoxic activity. Mechanistic studies reveal that mutations
      affecting R65 hinder membrane fusion in vitro by arresting the late steps of
      soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)
      complex assembly. Collectively, these results reveal a direct role for SEC/MUNC18
      proteins in promoting SNARE-complex assembly in vivo and suggest that STXBP2 R65
      mutations operate in a novel dominant-negative fashion to impair lytic granule
      fusion and contribute to HLH. 

PMID- 25564403
TI  - Characterization of an autosomal dominant bleeding disorder caused by a
      thrombomodulin mutation.
AB  - We describe a family with an autosomal dominant disorder characterized by severe
      trauma- and surgery-related bleeding. The proband, who experienced life
      threatening bleeding during a routine operation, had normal clotting times, but
      markedly reduced prothrombin consumption. Plasma levels of all coagulation
      factors and of the main coagulation inhibitors were normal. Thrombin generation
      at low triggers was severely impaired and mixing experiments suggested the
      presence of a coagulation inhibitor. Using whole exome sequencing, the underlying
      genetic defect was identified as the THBD c.1611C>A mutation (p.Cys537Stop),
      which predicts a truncated form of thrombomodulin that is shed from the vascular
      endothelium. The patient had decreased expression of endothelium-bound
      thrombomodulin, but extremely elevated levels of soluble thrombomodulin in
      plasma, impairing the propagation phase of coagulation via rapid activation of
      protein C and consequent inactivation of factors Va and VIIIa. The same
      thrombomodulin mutation has been recently described in an unrelated British
      family with strikingly similar features. 

PMID- 25564404
TI  - How I treat advanced classical Hodgkin lymphoma.
AB  - The development of curative systemic treatment of Hodgkin lymphoma was recently
      voted one of the top 5 achievements of oncology in the last 50 years
      (http://cancerprogress.net/top-5-advances-modern-oncology). The high expectation
      of cure (above 80%) with initial therapy, even for advanced disease, is tempered
      by the recognition of some important limitations: not all patients are cured,
      especially those in older age groups, and patients have suffered debilitating or,
      in some cases, fatal long-term side effects. The challenge for modern treatment
      approaches is to improve the cure rate and, at the same time, minimize the long
      term damage resulting from treatment. After several decades during which we have
      tested a variety of different ways to combine conventional cytotoxic treatments
      with or without radiotherapy but have identified no effective new approaches, the
      field is once again moving forward. The developments that hold the greatest
      promise in this respect are the application of functional imaging with (18)F
      fluorodeoxyglucose positron emission tomography (FDG-PET) to make an early
      judgment of the success of treatment and the introduction of some highly active
      new agents such as antibody-drug conjugates. 

PMID- 25564406
TI  - An uncommon presentation of a common pathogen.

PMID- 25564408
TI  - How polymer additives reduce the pour point of hydrocarbon solvents containing
      wax crystals.
AB  - We have investigated how four different pour point depressant (PPD) polymers
      affect the pour point transition in mixtures of a single pure wax in a solvent.
      We used either n-eicosane (C20), CH3(CH2)18CH3, n-tetracosane (C24),
      CH3(CH2)22CH3 or n-hexatriacontane (C36), CH3(CH2)34CH3 as the wax component with
      either n-heptane or toluene as the solvent component. For all wax-solvent
      combinations, the measured variation of wax solubility with temperature is well
      predicted by ideal solution theory. The variation of pour point temperature as a
      function of the overall wax concentration is quantitatively modelled using the
      idea that, for each overall wax concentration, the pour point occurs at a
      temperature at which a critical volume fraction phi* of wax crystals has
      precipitated. Close to the pour point temperature, extraction and examination of
      the wax crystals show they consist of polydisperse, irregularly-shaped platelets
      with axial ratios (h/d, where h is the plate thickness and d is the plate long
      dimension) in the range 0.005-0.05. It is found that the measured phi* values
      corresponding to the pour point transitions are weakly correlated with the wax
      crystal axial ratios (h/d) for all wax-solvent-PPD polymer combinations. These
      results indicate that the pour point transition occurs at a volume fraction
      larger than the value at which the volumes of rotation of the platelet crystals
      overlap, i.e., 2.5(h/d) < phi* < 11(h/d). PPD polymers work, in part, by
      increasing the wax crystal axial ratio (h/d), thereby increasing phi* and
      reducing the pour point temperature. Since the PPD's ability to modify the wax
      crystal shape relies on its adsorption to the crystal-solution surface, it is
      anticipated and observed experimentally that optimum PPD efficacy is correlated
      with the difference between the wax and the polymer solubility boundary
      temperatures. This finding and the mechanistic insight gained here provide the
      basis for a simple and rapid screening test to identify candidate species likely
      to be effective PPDs for particular wax systems. 

PMID- 25564407
TI  - Primary partial humeral head resurfacing: outcomes with the HemiCAP implant.
AB  - BACKGROUND: Humeral head defects such as degenerative disease or avascular
      necrosis are often treated with stemmed hemiarthroplasty or total shoulder
      arthroplasty. Despite its historical and clinical significance, stemmed humeral
      head replacement poses inherent technical challenges to placing spherical
      implants at the anatomically correct head height, version, and neck-shaft angle.
      PURPOSE: The aim of this study was to assess humeral head inlay arthroplasty as a
      joint-preserving alternative that maintains the individual head-neck-shaft
      anatomy. Humeral head inlay arthroplasty also allows intraoperative surface
      mapping and placement of a contoured articular component that is matched to the
      patient's defect size, location, and individual surface geometry. STUDY DESIGN:
      Case series; Level of evidence, 4. METHODS: This retrospective case series
      included 19 patients (20 shoulders), with an average age of 48.9 years (range, 32
      58 years; 16 men, 3 women). Preoperative diagnoses were osteoarthritis in 16
      shoulders and osteonecrosis in 4 shoulders. Pre- and postoperative evaluations
      included physical examination, radiographic assessment, the American Shoulder and
      Elbow Surgeons Standardized Shoulder Assessment Form, the Simple Shoulder Test, a
      pain visual analog scale, and patient satisfaction rating. RESULTS: The mean
      follow-up period was 32.7 months (range, 17-66 months). The mean American
      Shoulder and Elbow Surgeons score improved from 24.1 to 78.8, mean Simple
      Shoulder Test score from 3.95 to 9.3, mean visual analog scale score from 8.2 to
      2.1, mean forward flexion from 100 degrees  to 129 degrees , and mean external
      rotation from 23 degrees  to 43 degrees  (P < .001 for all). Radiographic follow
      up showed no evidence of periprosthetic fracture, component loosening,
      osteolysis, or device failure. Patient shoulder self-assessment was 90% poor
      before surgery and improved to 75% good to excellent at last follow-up; 20% of
      patients self-rated as somewhat good to somewhat poor, and 5% self-rated as poor.
      Ninety percent of patients were satisfied with the choice of the procedure. Three
      patients had postoperative complications unrelated to the implants, including a
      partial rotator cuff tear treated with physical therapy, preexisting glenoid wear
      treated with arthroscopic debridement and microfracture, and infection
      complicated by subscapularis rupture requiring several subsequent surgical
      procedures but with retention of the implant. CONCLUSION: Humeral head inlay
      arthroplasty is effective in providing pain relief, functional improvement, and
      patient satisfaction. Rather than delaying shoulder arthroplasty to end-stage
      osteoarthritis, humeral head inlay arthroplasty is a promising new direction in
      primary shoulder arthroplasty for younger and active patients with earlier stage
      disease.

PMID- 25564405
TI  - Two types of BCR interactions are positively selected during leukemia development
      in the EMU-TCL1 transgenic mouse model of CLL.
AB  - Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy characterized by
      a highly variable course and outcome. The disease is believed to be driven by B
      cell receptor (BCR) signals generated by external antigens and/or cell-autonomous
      BCR interactions, but direct in vivo evidence for this is still lacking. To
      further define the role of the BCR pathway in the development and progression of
      CLL, we evaluated the capacity of different types of antigen/BCR interactions to
      induce leukemia in the EMU-TCL1 transgenic mouse model. We show that cell
      autonomous signaling capacity is a uniform characteristic of the leukemia-derived
      BCRs and represents a prerequisite for CLL development. Low-affinity BCR
      interactions with autoantigens generated during apoptosis are also positively
      selected, suggesting that they contribute to the pathogenesis of the disease. In
      contrast, high-affinity BCR interactions are not selected, regardless of antigen
      form or presentation. We also show that the capacity of the leukemic cells to
      respond to cognate antigen correlates inversely with time to leukemia
      development, suggesting that signals induced by external antigen increase the
      aggressiveness of the disease. Collectively, these findings provide in vivo
      evidence that the BCR pathway drives the development and can influence the
      clinical course of CLL. 

PMID- 25564409
TI  - Single versus double balloon enteroscopy for small bowel diagnostics: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Double balloon enteroscopy (DBE) and single balloon enteroscopy
      (SBE) are 2 types of commonly used balloon-assisted enteroscopic techniques for
      "deep enteroscopy." Although there are several randomized controlled trials
      assessing the superiority of DBE compared with SBE, the results from individual
      randomized controlled trials seem conflicting. We performed a systematic review
      and meta-analysis to assess the efficacy of DBE compared with SBE. METHODS:
      Primary outcomes were diagnostic and therapeutic yield. Secondary outcomes were
      failure rates, adverse events, complete enteroscopy, anterograde/retrograde
      insertion depths, and procedure times. We searched MEDLINE and the Cochrane
      Central Register of Controlled Trials (CENTRAL) from inception until February 28,
      2014, as well as other databases. For quality assurance purposes throughout the
      systematic review process, dual extraction was performed. The systematic review
      was performed as per the standards of Cochrane collaboration. RESULTS: Four
      trials enrolling a total of 375 patients were included. DBE did not offer an
      advantage over SBE in therapeutic yield [risk ratio (RR), 1.11; 95% confidence
      interval (CI): 0.90, 1.37; P=0.33)] or diagnostic yield (RR=1.08; 95% CI: 0.89,
      1.32; P=0.42), failure rates (RR=0.68; 95% CI: 0.23, 2.05; P=0.5), overall
      adverse events (RR=1.41; 95% CI: 0.32, 6.3; P=0.65), or complete enteroscopy
      rates (RR=1.73; 95% CI: 0.86, 3.48; P=0.12). No evidence existed for an advantage
      of anterograde or retrograde procedure time between these 2 modalities [mean
      difference (MD), 3.78; 95% CI, -30.76, 38.32; P=0.83; and MD, -0.53; 95% CI: 
      7.66, 6.59; P=0.88, respectively]. Neither anterograde nor retrograde insertion
      depths appeared to differ between the 2 studies analyzed (MD, -7.36; 95% CI: 
      40.36, 25.64; P=0.66 and MD, 7.86; 95% CI: -12.68, 28.40; P=0.45, respectively).
      CONCLUSIONS: Performance of SBE and DBE appears to be similar in terms of
      diagnostic/therapeutic yield, insertion depths, procedure time, complete
      enteroscopy, failure rates, or adverse events.

PMID- 25564410
TI  - Celiac Disease in Women With Infertility: A Meta-Analysis.
AB  - BACKGROUND: Celiac disease (CeD) is a systemic disease with manifestations not
      limited to small intestine. The data on association between CeD and infertility
      is contradictory. There are no recommendations for the screening of female
      patients with infertility for CeD. AIM: We conducted a meta-analysis to find out
      whether women with infertility are at higher risk of CeD. METHODS: Literature
      search was performed using the MeSH keywords "CeD," "gluten," and "infertility."
      Diagnosis of CeD was based on positive serology and biopsies showing villous
      atrophy. Data were extracted about CeD patients in 3 groups-women with
      infertility (including unexplained infertility), unexplained infertility, and
      controls. Pooled odds ratio (OR) and prevalence, with 95% confidence intervals
      (CI), were calculated. RESULTS: Of 105 relevant studies, 5 studies were included
      for calculation of pooled OR. Four additional studies, where data on controls
      were not available, were also considered for calculation of pooled prevalence of
      CeD. Women with infertility had 3.5 times higher odds of having CeD in comparison
      with control population (OR=3.5; 95% CI, 1.3-9; P<0.01). Similarly, women with
      "unexplained infertility" had 6 times higher odds of having CeD than controls
      (OR=6; 95% CI, 2.4-14.6). Of 884 women with infertility, 20 had CeD indicating a
      pooled prevalence of 2.3% (95% CI, 1.4-3.5). Of 623 women with "unexplained
      infertility," 20 had CeD. The pooled prevalence of CeD in women with unexplained
      infertility was 3.2 (95% CI, 2-4.9). CONCLUSIONS: CeD is more prevalent in women
      with "all-cause" infertility and "unexplained" infertility than that in general
      population.

PMID- 25564411
TI  - Hepatectomy Versus Hepatectomy With Lymphadenectomy in Hepatocellular Carcinoma:
      A Prospective, Randomized Controlled Clinical Trial.
AB  - GOALS AND BACKGROUND: The role of preventive lymphadenectomy has not yet been
      determined for hepatocellular carcinoma (HCC) patients. We designed a study to
      evaluate the effect of hepatectomy combined with preventive lymphadenectomy on
      HCC patients. STUDY: Patients were randomly divided into group A (treated with
      hepatectomy alone) and group B (underwent hepatectomy combined with
      lymphadenectomy). The postoperative complications and oncologic prognoses were
      analyzed. RESULTS: Of the 85 patients enrolled into this study, 79 cases (38 in
      group A and 41 in group B) were pathologically confirmed to have HCC and received
      curative resection. One hundred and sixteen lymph nodes were dissected and
      evaluated as negative by the pathologist. The 12-, 36-, and 60-month disease-free
      survival rates of group A were 81.6%, 68.4%, and 63.2%, respectively, whereas
      they were 78.0%, 65.9%, and 63.4%, respectively, for group B. The 12-, 36-, and
      60-month overall survival rates in group A were 94.7%, 78.9%, and 65.8%,
      respectively, whereas they were 87.8%, 78.0%, and 70.7%, respectively, in group
      B. The differences in the disease-free survival and overall survival between the
      2 groups were not statistically significant according to the log-rank test
      (P=0.811 and P=0.881, respectively). The difference in the surgical complication
      rate between groups A and B was not statistically significant (47.4% vs. 36.6%,
      P=0.332). CONCLUSIONS: Although hepatectomy combined with regional
      lymphadenectomy is a safe procedure, preventive lymphadenectomy may not decrease
      the rate of tumor recurrence nor improve the prognosis in early-stage HCC
      patients.

PMID- 25564412
TI  - Nanoscale stabilization of the scheelite-type structure in La(0.99)Ca(0.01)NbO4
      thin films.
AB  - In this paper we report on the deposition of La0.99Ca0.01NbO4 thin films with
      scheelite-type crystal structure. Thanks to the film's nanostructure, we were
      able to stabilize the tetragonal scheelite-type structure phase at room
      temperature, which involves a full removal of the fergusonite-scheelite phase
      transition. 

PMID- 25564413
TI  - A crosstalk between Na+ channels, Na+/K+ pump and mitochondrial Na+ transporters
      controls glucose-dependent cytosolic and mitochondrial Na+ signals.
AB  - Glucose-dependent cytosolic Na(+) influx in pancreatic islet beta cells is
      mediated by TTX-sensitive Na(+) channels and is propagated into the mitochondria
      through the mitochondrial Na(+)/Ca(2+) exchanger, NCLX. Mitochondrial Na(+)
      transients are also controlled by the mitochondrial Na(+)/H(+) exchanger, NHE,
      while cytosolic Na(+) changes are governed by Na(+)/K(+) ATPase pump. The
      functional interaction between the Na(+) channels, Na(+)/K(+) ATPase pump and
      mitochondrial Na(+) transporters, NCLX and NHE, in mediating Na(+) signaling is
      poorly understood. Here, we combine fluorescent Na(+) imaging, pharmacological
      inhibition by TTX, ouabain and EIPA, with molecular control of NCLX expression,
      so as to investigate the crosstalk between Na(+) transporters on both the plasma
      membrane and the mitochondria. According to our results, glucose-dependent
      cytosolic Na(+) response was enhanced by ouabain and was followed by a rise in
      mitochondrial Na(+) signal. Silencing of NCLX expression using siNCLX, did not
      affect the glucose- or ouabain-dependent cytosolic rise in Na(+). In contrast,
      the ouabain-dependent rise in mitochondrial Na(+) was strongly suppressed by
      siNCLX. Furthermore, mitochondrial Na(+) influx rates were accelerated in cells
      treated with the Na(+)/H(+) exchanger inhibitor, EIPA or by combination of EIPA
      and ouabain. Similarly, TTX blocked the cytosolic and mitochondrial Na(+)
      responses, which were enhanced by ouabain or EIPA, respectively. Our results
      suggest that Na(+)/K(+) ATPase pump controls cytosolic glucose-dependent Na(+)
      rise, in a manner that is mediated by TTX-sensitive Na(+) channels and subsequent
      mitochondrial Na(+) uptake via NCLX. Furthermore, these results indicate that
      mitochondrial Na(+) influx via NCLX is antagonized by Na(+) efflux, which is
      mediated by the mitochondrial NHE; thus, the duration of mitochondrial Na(+)
      transients is set by the interplay between these pivotal transporters. 

PMID- 25564414
TI  - Traditional pig farming practices and productivity in the Jayawijaya region,
      Papua Province, Indonesia.
AB  - The objective of the current survey was to provide an update on pig farming
      practices in the Jayawijaya region, Papua Province, Indonesia. A structured semi
      close-ended questionnaire was used to interview 367 farmers across the Jayawijaya
      region. Results showed that farms, on average, comprised of 8.8 pigs (CI 8.5
      9.1). The average litter size was 6.0 (CI 5.7-6.3) piglets, the farrowing
      frequency was once a year, and the annual mortality rate was 50.2% (CI 48.4
      51.9). On average, 43.4% farms (CI 36.4-50.7) allowed pigs to roam freely during
      daylight hours. Farmers used pigs for their own consumption (62.4%, CI 57.4
      67.4), as a gift (56.6%, CI 51.5-61.7), or for sale (50.7%, CI 45.6-55.8).
      Veterinary services were used intensively by just 11.7% of farmers (CI 8.2-16.5).
      Furthermore, 34.2% (CI 29.3-39) of farmers would sell sick pigs, and 63.1% (CI
      58.2-68.1) would slaughter and consume them. It was also recorded that 68.6% of
      farmers (CI 63.7-73.4) would eat sick pigs that had died naturally. These
      findings suggest that traditional pig farms in Jayawijaya are of low
      productivity. Moreover, the free roaming of pigs and the sale and consumption of
      sick pigs have the potential to allow pathogens to circulate between pig and
      human populations.

PMID- 25564415
TI  - Socioeconomic and productive characterization of dual-purpose farms oriented to
      milk production in a subtropical region of Mexico.
AB  - The aim of this study was to determine the socioeconomic, production
      characteristics and milk production cost of dual-purpose farms (DPF) oriented to
      milk production in a subtropical region of Central Mexico. The study focused on
      ten DPF that produce milk all year round, to gather socioeconomic characteristics
      of farmers (age, family structure, education level), farm resources (land
      holding, herd structure, infrastructure, management) and economic information
      during the year 2008. Family labour (FL) covers 66% of labour needs. The average
      milk production cost was US$0.21, fluctuating from US$0.19 to US$0.31 during the
      rainy and dry season, respectively. Supplements and hired labour (HL) accounted
      for 48 and 35% of milk production cost, respectively. Milk production generated
      daily incomes that covered daily operation costs of farms, as well as the
      economic needs of the farming family. Calves represented important incomes that
      ranged between 30 and 50% of total annual farm incomes, cashed in once or twice a
      year. Milk production provides economic stability to DPF, whereas FL and low
      input use are key elements that allow low costs in the production of milk and
      calves in DPF in Central Mexico.

PMID- 25564416
TI  - Association of MTHFR C677T with total homocysteine plasma levels and
      susceptibility to Parkinson's disease: a meta-analysis.
AB  - The C677T single-nucleotide polymorphism in the methylenetetrahydrofolate
      reductase gene (MTHFR) may elevate homocysteine (Hcy) levels and increase the
      risk of Parkinson's disease (PD); however, results are conflicting. Our aim was
      to resolve contradictions in the literature and to determine whether MTHFR C677T
      has a significant role in regulating Hcy levels and/or is a significant risk
      factor for PD. MEDLINE, EMBASE, the Cochrane Library, China Biological Medicine
      Database and Google Scholar were searched until May 2014. Strict selection and
      exclusion criteria were determined, and odds ratios (ORs)/weighted mean
      differences (WMDs) with 95 % confidence intervals (CIs) were used to assess the
      strength of associations. Statistical analyses were performed using STATA 12.0.
      Fifteen studies that together assessed 2690 PD cases and 8465 controls were
      included. Meta-analysis showed that no significant difference in the distribution
      of MTHFR C677T between PD cases and controls was found. While stratifying for
      ethnicity, significant association was revealed in Europeans (T vs. C, OR = 1.17,
      95 % CIs 1.04-1.31) but not in Asians. Significant association between the T
      allele and increased Hcy levels was found in PD cases and controls; Hcy levels
      were higher in PD cases and controls carrying the MTHFR T677 allele than in non
      carriers (TT vs. CC, PD WMD = 6.50, 95 % CIs 6.20-6.80; controls WMD = 4.52, 95 %
      CIs 4.24-4.80). Other within-group comparisons showed similar results. This meta
      analysis suggests that MTHFR C667T may confer PD susceptibility in Europeans. The
      T allele may be an independent risk factor for elevated Hcy levels in PD
      patients.

PMID- 25564417
TI  - Clinical variables associated with treatment changes in Parkinson's disease:
      results from the longitudinal phase of the REASON study.
AB  - To assess over a period of 9 months in a sample of Italian Parkinson's disease
      (PD) patients reasons leading the neurologist to modify dopaminergic treatment
      and patients' causes of dissatisfaction with ongoing therapy. To evaluate the
      influence of disease severity on therapy persistence. A disease severity balanced
      sample of PD patients with stable anti-parkinsonian drugs (APD) treatment was
      enrolled and evaluated every 3 months. Patients requiring APD treatment
      modifications were discontinued from the study. The probability to modify APD
      treatment is greater for higher motor (UPDRS scores) and non-motor symptoms (NMSS
      score) severity. Both from neurologist's and patient's perspective, motor
      symptoms were the main determinants underlying APD treatment modifications. Non
      motor symptoms were cause of dissatisfaction with ongoing APD treatment for 52 %
      of the patients, while only 36 % of the neurologists considered these as valid
      reasons for therapy change. REASON is the first study in PD patients that
      prospectively examined reasons driving APD treatment changes. Results show that
      the disease severity significantly increases the probability of APD treatment
      change. Patients attribute greater relevance than neurologists to non-motor
      symptoms as reason requiring treatment changes. This confirms that patient and
      neurologist perceptions only partially overlap.

PMID- 25564418
TI  - Potential impact of climatic variability on the epidemiology of dengue in
      Risaralda, Colombia, 2010-2011.
AB  - Dengue continues to be the most important viral vector-borne disease in the
      world, particularly in Asia and Latin America, and is significantly affected by
      climate variability. The influence of climate in an endemic region of Colombia,
      from 2010 to 2011, was assessed. Epidemiological surveillance data (weekly cases)
      were collected, and incidence rates were calculated. Poisson regression models
      were used to assess the influence of the macroclimatic variable ONI (Oscillation
      Nino Index) and the microclimatic variable pluviometry (mm of rain for Risaralda)
      on the dengue incidence rate, adjusting by year and week. During the study
      period, 13,650 cases were reported. In 2010, the rates ranged from 8.6
      cases/100,000 pop. up to a peak of 75.3 cases/100,000 pop. for a cumulative rate
      of 456.2 cases/100,000 pop. in that week. The climate variability in 2010 was
      higher (ONI 1.6, El Nino to -1.5, La Nina) than in 2011 (ONI -1.4, La Nina to 
      0.2, Neutral). The mean pluviometry was 248.45mm (min 135.9-max 432.84). During
      El Nino, cases were significantly higher (mean 433.81) than during the climate
      neutral period (142.48) and during the La Nina (52.80) phases (ANOVA F=66.59;
      p<0.001). Regression models showed that the ONI (coefficient 0.329; 95%CI 0.209
      0.450) and pluviometry (coefficient 0.003; 95%CI 0.002-0.004) were highly
      significant independent variables associated with dengue incidence rate, after
      adjusting by year and week (p<0.001, pseudo r(2)=0.6913). El Nino significantly
      affected the incidence of dengue in Risaralda. This association with climate
      change and variability should be considered in the elements influencing disease
      epidemiology. In addition, predictive models should be developed further with
      more available data from disease surveillance.

PMID- 25564419
TI  - Dissemination of aerosol and splatter during ultrasonic scaling: a pilot study.
AB  - CONTEXT: Routine dental procedures produce aerosol and splatter, which pose a
      potential risk to the clinician and dental personnel, as well as the
      immunocompromised patient. Reports indicate that the ultrasonic scaler is the
      greatest producer of aerosol and splatter. AIMS: The study aimed to evaluate the
      contamination distance, contamination amount and contamination duration of
      aerosol produced during ultrasonic scaling. METHODS AND MATERIALS: The study was
      performed on a mannequin fitted with phantom jaws on a dental chair. Mock scaling
      was done for 15 min using an auto-tuned magnetostrictive ultrasonic scaler with
      the simultaneous use of a low volume saliva ejector. An ultrafiltrate-containing
      fluorescent dye was used in the reservoir supplying the scaler unit. Filter paper
      discs were placed in different positions and distances in the operatory.
      Immediately following scaling, the filter paper discs were replaced with new
      ones. This was done every 30 min for a total duration of 90 min. RESULTS: Maximum
      contamination was found on the right arm of the operator and left arm of the
      assistant. Contamination was also found on the head, chest and inner surface of
      the face mask of the operator and of the assistant. The aerosol was found to
      remain in the air up to 30 min after scaling. CONCLUSIONS: The occupational
      health hazards of dental aerosols can be minimized by following simple,
      inexpensive precautions.

PMID- 25564420
TI  - Reproducibility of computed tomography to evaluate ankle and hindfoot fusions;
      statistical issue to avoid misinterpretation.

PMID- 25564421
TI  - Response to Sabour, "reproducibility of computed tomography to evaluate ankle and
      hindfoot fusions; statistical issue to avoid misinterpretation".

PMID- 25564422
TI  - Carbofuran alters centrosome and spindle organization, and delays cell division
      in oocytes and mitotic cells.
AB  - Although many countries banned of its usage, carbofuran (CF) is still one of the
      most commonly used carbamate derivative insecticides against insects and
      nematodes in agriculture and household, threatening the human and animal health
      by contaminating air, water, and food. Our goal was to evaluate the potential
      toxic effects of CF on mammalian oocytes besides mitotic cells. Caspase-dependent
      apoptotic pathway was assessed by immunofluorescence and western blot techniques.
      Alterations in the meiotic spindle formation after CF exposure throughout the in
      vitro maturation of mice oocyte-cumulus complexes (COCs) were analyzed by using a
      3D confocal laser microscope. Maturation efficiency and kinetics were assessed by
      direct observation of the COCs. Results indicated that the number of TUNEL
      positive cells increased in CF-exposed groups, particularly higher doses (>250
      uM) in a dose-dependent fashion. The ratio of anticleaved caspase-3 labeled cells
      in those groups positively correlated with TUNEL-positivity. Western blot
      analysis confirmed a significant increase in active caspase-3 activity. CF caused
      a dose-dependent accumulation of oocytes at prometaphase-I (PM-I) of meiosis.
      Partial loss of spindle microtubules (MTs) was noted, which consequently gave
      rise to a diamond shape spindle. Aberrant pericentrin foci were noted
      particularly in PM-I and metaphase-I (M-I) stages. Conclusively, CF (1) induces
      programmed cell death in a dose-dependent manner, and (2) alters spindle
      morphology most likely through a mechanism that interacts with MT assembly and/or
      disorientation of pericentriolar proteins. Overall, data suggest that CF could
      give rise to aneuploidy or cell death in higher doses, therefore reduce
      fertilization and implantation rates.

PMID- 25564424
TI  - Temporal changes in biological responses and uncertainty in assessing risks of
      endocrine-disrupting chemicals: insights from intensive time-course studies with
      fish.
AB  - Most toxicological testing focuses on defining concentration/dose-response
      relationships, with little consideration to temporal aspects of the expression of
      chemical effects. Yet, both dose and time are critical to evaluating potential
      risks. Our lab has generated an extensive amount of linked dose-response and time
      course data for eight model endocrine-disrupting chemicals (EDCs) using adult
      fathead minnows (Pimephales promelas). Herein we conduct a meta-analysis of this
      novel dataset, with an emphasis on defining interactions between dose and time on
      several molecular and biochemical endpoints indicative of endocrine function,
      both during chemical exposure and recovery. Direct effects of the EDCs were very
      rapid, often occurring within 24 h or less. Recovery after removal of the
      chemical stressors was similarly rapid. All experiments provided evidence of
      system compensation. For example, measures of endocrine perturbation early in an
      experiment, especially in low-dose treatments, often recovered to control values
      while a chemical exposure was ongoing. In experiments with several of the EDCs,
      shortly after cessation of the chemical exposure there was an "overshoot"
      behavior, in which different measures of endocrine function exceeded control
      values. Overall, when an endpoint was measured was as an important determinant in
      identifying a chemical as endocrine-active, as the dose to which the animal was
      exposed. The compensatory responses during exposure and early recovery after
      removal of the chemical stressor also produced examples of nonmonotonic dose
      response relationships. The types of interactions between time and dose observed
      in these studies have a number of important implications for screening, testing,
      and monitoring programs for EDCs.

PMID- 25564423
TI  - Role of miRNA in the regulation of inflammatory genes in staphylococcal
      enterotoxin B-induced acute inflammatory lung injury and mortality.
AB  - Exposure to Staphylococcal enterotoxin B (SEB) causes food poisoning, acute
      inflammatory lung injury, toxic shock syndrome, and often death. In this study,
      we investigated whether microRNA (miRNA) play a role in regulating SEB-driven
      inflammation in the lungs. Exposure to SEB caused immune cell infiltration,
      robust cytokine and chemokine production, compromised lung function, and 100%
      mortality in mice. We assessed miRNA and mRNA expression in lung infiltrating
      mononuclear cells following exposure to SEB and found 89 miRNA that were
      dysregulated (>2-fold) compared with vehicle controls. In silico analysis
      revealed that the miRNA exhibited biological functions pertaining to cell death
      and survival, cellular proliferation, and cell cycle progression. Through the use
      of q-RT PCR, we validated 9 specific miRNA (miR-155, miR-132, miR-31, miR-222,
      miR-20b, miR-34a, miR-192, miR-193*, and let-7e) and observed that they were
      predicted to bind the 3'-UTR of a number of genes that were either involved in
      the stringent regulation of inflammation (Smad3, Tgfb, Runx1, and Foxo3) or those
      that contributed to its exacerbation (Stat3, Ptgs2, Ccnd1, Ccne1, NfkappaB, and
      Tbx21). Further, by increasing or decreasing the levels of miR-132 (a miRNA
      highly induced by SEB), we noted the corresponding decrease or increase in the
      levels of its predicted target FOXO3. As a result of FOXO3 suppression by miR
      132, we saw increase in Ifn-gamma, Ccnd, and Ccne1. Taken together, our data
      support the role for miRNA in actively participating and orchestrating SEB
      mediated inflammation in the lungs and provide several therapeutic targets for
      the treatment of SEB-driven toxicity via the modulation of miRNA. 

PMID- 25564425
TI  - Zinc Deficiency With Dermatitis in a Parenteral Nutrition-Dependent Patient Due
      to National Shortage of Trace Minerals.
AB  - The shortages of intravenous drugs remains critical, with sterile injectables
      accounting for 80% of the approximately 300 shortages. The impact is being felt
      in patients dependent on parenteral nutrition (PN), and severe deficiencies are
      becoming more commonplace. We report here a man who developed severe zinc
      deficiency, manifesting as a painful desquamative rash, due to an inability to
      obtain multi-trace element additives for his PN.

PMID- 25564426
TI  - Thiamin in Clinical Practice.
AB  - Thiamin is a water-soluble vitamin also known as vitamin B1. Its biologically
      active form, thiamin pyrophosphate (TPP), is a cofactor in macronutrient
      metabolism. In addition to its coenzyme roles, TPP plays a role in nerve
      structure and function as well as brain metabolism. Signs and symptoms of thiamin
      deficiency (TD) include lactic acidosis, peripheral neuropathy, ataxia, and
      ocular changes (eg, nystagmus). More advanced symptoms include confabulation and
      memory loss and/or psychosis, resulting in Wernicke's encephalopathy and/or
      Wernicke's Korsakoff syndrome, respectively. The nutrition support clinician
      should be aware of patients who may be at risk for TD. Risk factors include those
      patients with malnutrition due to 1 or more nutrition-related etiologies:
      decreased nutrient intake, increased nutrient losses, or impaired nutrient
      absorption. Clinical scenarios such as unexplained heart failure or lactic
      acidosis, renal failure with dialysis, alcoholism, starvation, hyperemesis
      gravidarum, or bariatric surgery may increase the risk for TD. Patients who are
      critically ill and require nutrition support may also be at risk for TD,
      especially those who are given intravenous dextrose void of thiamin repletion.
      Furthermore, understanding thiamin's role as a potential therapeutic agent for
      diabetes, some inborn errors of metabolism, and neurodegenerative diseases
      warrants further research. This tutorial describes the absorption, digestion, and
      metabolism of thiamin. Issues pertaining to thiamin in clinical practice will be
      described, and evidence-based practice suggestions for the prevention and
      treatment of TD will be discussed. 

PMID- 25564427
TI  - Energy Expenditure in Patients With Esophageal, Gastric, and Colorectal Cancer.
AB  - BACKGROUND: Changes in resting energy expenditure (REE) appear to be one of the
      causes of nutritional depletion in cancer. Assessing REE may be an important tool
      for providing adequate nutritional therapy to these patients. The aims of this
      study were to evaluate REE of patients with gastrointestinal tract cancer and to
      compare it to that of healthy controls. METHODS: A total of 20 patients, with
      esophageal (n = 3), gastric (n = 9), and colorectal (n = 8) cancers, and 20
      healthy subjects were included. Indirect calorimetry (IC) was used to measure REE
      in both groups. The "pocket" equation (30 kcal/kg) and the Harris-Benedict
      equation, with correction factors of 1.3 (activity) and 1.1 (injury), were
      employed for assessment of the estimated total energy expenditure (TEE).
      Statistics included Mann-Whitney and paired t tests, Bland Altman analysis, and
      multivariate regression. RESULTS: The REE of the patients (1,274.5 kcal [1,002.9
      2,174.9]) was similar to that of the controls (1,445.5 kcal [1,114.5-1,762.6],
      not significant), even when corrected for the amount of metabolically active
      tissue. The pocket equation was effective in predicting the patients' TEE, with a
      1.7% (32 kcal) difference being observed in comparison with the IC results
      corrected with the activity factor (not significant). CONCLUSIONS: The patients
      with digestive tract cancers showed a similar REE to that of the controls. The
      current formula of 30 kcal/kg is suitable for estimating the TEE of these
      patients.

PMID- 25564429
TI  - Communicable disease X (Ebola, MERS, TB, measles...)--coming soon to a
      neighborhood near you? Lessons learned about communicable disease and air travel.

PMID- 25564430
TI  - Metal-free Lewis acid mediated dehydrocoupling of phosphines and concurrent
      hydrogenation.
AB  - The stoichiometric reaction of trityl cation with two equivalents of Ph2PH
      affords the phosphine stabilized phosphenium salt [Ph2(H)PPPh2][B(C6F5)4] via
      hydride abstraction, while catalytic amounts of B(p-HC6F4)3 effects catalytic
      phosphine dehydrocoupling with the liberation of H2. This reaction is accelerated
      by the presence of olefin or imine, effecting concurrent hydrogenation. 

PMID- 25564431
TI  - Building biophysics in mid-century China: the University of Science and
      Technology of China.
AB  - Biophysics has been either an independent discipline or an element of another
      discipline in the United States, but it has always been recognized as a stand
      alone discipline in the People's Republic of China (PRC) since 1949. To inquire
      into this apparent divergence, this paper investigates the formational history of
      biophysics in China by examining the early institutional history of one of the
      best-known and prestigious science and technology universities in the PRC, the
      University of Science and Technology of China (USTC). By showing how the
      university and its biophysics program co-evolved with national priorities from
      the school's founding in 1958 to the eve of the Cultural Revolution in 1966, the
      purpose of this paper is to assess the development of a scientific discipline in
      the context of national demands and institutional politics. Specific materials
      for analysis include the school's admission policies, curricula, students'
      dissertations, and research program. To further contextualize the institutional
      setting of Chinese biophysics, this paper begins with a general history of proto
      biophysical institutions in China during the Nationalist-Communist transitional
      years. This paper could be of interest to historians wanting to know more about
      the origin of the biophysics profession in China, and in particular how research
      areas that constitute biophysics changed in tandem with socio-political
      contingencies. 

PMID- 25564428
TI  - Plasma 25-Hydroxyvitamin D Levels at Initiation of Care and Duration of
      Mechanical Ventilation in Critically Ill Surgical Patients.
AB  - OBJECTIVE: Limited data exist regarding the relationship between plasma 25
      hydroxyvitamin D levels and duration of respiratory support. Our goal was to
      explore whether vitamin D status at the time of intensive care unit (ICU)
      admission is associated with duration of mechanical ventilation in critically ill
      surgical patients. MATERIALS AND METHODS: We analyzed data from a prospective
      cohort study involving 210 critically ill surgical patients. To explore the
      relationship between admission plasma 25-hydroxyvitamin D levels and duration of
      mechanical ventilation, we performed a Poisson regression while controlling for
      clinically relevant covariates. Only patients who required >=48 hours of
      mechanical ventilation and survived >=24 hours after discontinuation of
      respiratory support were included in the analytic cohort. RESULTS: Ninety-four
      patients met inclusion criteria. Mean (standard deviation) plasma 25
      hydroxyvitamin D level was 16 (7) ng/mL and median (interquartile range) duration
      of mechanical ventilation was 4 (2-7) days. Poisson regression analysis, adjusted
      for age, sex, race, body mass index, primary surgical service, Acute Physiology
      and Chronic Health Evaluation II score, and season of ICU admission, demonstrated
      an inverse association of plasma 25-hydroxyvitamin D levels with duration of
      mechanical ventilation (incident rate ratio per 10 ng/mL, 0.66; 95% confidence
      interval, 0.54-0.82). CONCLUSIONS: In our cohort of critically ill surgical
      patients, plasma 25-hydroxyvitamin D levels measured on ICU admission were
      inversely associated with the duration of respiratory support. Randomized
      controlled trials are needed to assess whether vitamin D supplementation can
      influence duration of mechanical ventilation in surgical ICU patients.

PMID- 25564433
TI  - Digital sleep logs reveal potential impacts of modern temporal structure on class
      performance in different chronotypes.
AB  - Stability of sleep and circadian rhythms are important for healthy learning and
      memory. While experimental manipulations of lifestyle and learning outcomes
      present major obstacles, the ongoing increase in data sources allows
      retrospective data mining of people's sleep timing variation. Here I use digital
      sleep-log data generated by 1109 students in a biology lab course at the
      University of Washington to test the hypothesis that higher variance in time
      asleep and later sleep-onset times negatively correlate with class performance,
      used here as a real-world proxy for learning and memory. I find that sleep
      duration variance and mean sleep-onset times both significantly correlate with
      class performance. These correlations are powerful on weeknights but undetectable
      on Friday and Saturday nights ("free nights"). Finally, although these data come
      with no demographic information beyond sex, the constructed demographic groups of
      "larks" and "owls" within the sexes reveal a significant decrease in performance
      of owls relative to larks in male students, whereas the correlation of
      performance with sleep-onset time for all male students was only a near
      significant trend. This provides a proof of concept that deeper demographic
      mining of digital logs in the future may identify subgroups for which certain
      sleep phenotypes have greater predictive value for performance outcomes. The data
      analyzed are consistent with known patterns, including sleep-timing delays from
      weeknights to free nights and sleep-timing delays in men relative to women. These
      findings support the hypothesis that modern schedule impositions on sleep and
      circadian timing have consequences for real-world learning and memory. This study
      also highlights the low-cost, large-scale benefits of personal, daily, digital
      records as an augmentation of sleep and circadian studies. 

PMID- 25564435
TI  - Challenges in assessing the process-outcome link in practice.
AB  - The expanded use of clinical process-of-care measures to assess the quality of
      health care in the context of public reporting and pay-for-performance
      applications has led to a desire to demonstrate the value of such efforts in
      terms of improved patient outcomes. The inability to observe associations between
      improved delivery of clinical processes and improved clinical outcomes in
      practice has raised concerns about the value of holding providers accountable for
      delivery of clinical processes of care. Analyses that attempt to investigate this
      relationship are fraught with many challenges, including selection of an
      appropriate outcome, the proximity of the outcome to the receipt of the clinical
      process, limited power to detect an effect, small expected effect sizes in
      practice, potential bias due to unmeasured confounding factors, and difficulties
      due to changes in measure specification over time. To avoid potentially
      misleading conclusions about an observed or lack of observed association between
      a clinical process of care and an outcome in the context of observational
      studies, individuals conducting and interpreting such studies should carefully
      consider, evaluate, and acknowledge these types of challenges. 

PMID- 25564436
TI  - Mechanisms of atherogenesis and development of anti-atherosclerotic therapy.

PMID- 25564434
TI  - The Economic Burden of Obesity by Glycemic Stage in the United States.
AB  - BACKGROUND: Electronic medical records and insurance claims data from the
      Geisinger Health System were examined to assess the real-world healthcare costs
      of being overweight or obese at different glycemic stages, including normal
      glycemia, pre-diabetes (PreD), and type 2 diabetes (T2D). METHODS: The medical
      history of the sample subjects was segmented into different glycemic stages via
      diagnosis codes, glycosylated hemoglobin A1c or fasting plasma glucose laboratory
      results, and use of antidiabetic drugs. Healthcare resource utilization captured
      by the claims and associated costs (in 2013 values) were examined for each
      glycemic stage. The association between costs and body mass index (BMI) was
      estimated by regressions, and adjusted for sociodemographics. We predicted the
      adjusted incremental annual costs associated with high BMI, relative to normal
      BMI (18.5-24.9 kg/m(2)). RESULTS: We identified 48,344 adults in normal glycemic
      stage, 3,085 in the PreD stage, and 9,526 in the T2D stage (mean age 46, 58, and
      60 years, respectively; mean BMI 29, 32, and 33 kg/m(2), respectively). The
      adjusted incremental annual costs associated with high BMI relative to normal BMI
      ranged from $336 for overweight (25-29.9 kg/m(2)) to $1,850 for class III obesity
      (>=40 kg/m(2)) during normal glycemic stage; were only significant for class III
      ($2,434) during the PreD stage; and ranged from $1,139 for overweight to $4,649
      for class III during the T2D stage (all p < 0.05). CONCLUSIONS: Positive
      associations between healthcare costs and BMI levels were observed within each
      glycemic stage. Management of body weight is important in reducing the overall
      healthcare costs, especially for subjects with PreD or T2D.

PMID- 25564432
TI  - Early developmental exposure to high fructose intake in rats with NaCl
      stimulation causes cardiac damage.
AB  - PURPOSE: Metabolic syndrome (MS) increases the risk of type 2 diabetes and
      cardiovascular disease. High consumption of fructose is a proposed cause of
      increased MS, manifested through hypertension, obesity, insulin resistance, and
      dyslipidemia. High NaCl also increases the risk of CD. The purpose of this study
      is to evaluate the influence of fructose and sodium on autonomic dysfunction and
      its relation with CD in MS. Fructose overload was started at weaning and
      continued through adulthood. METHODS: Male Wistar rats (21 days) were divided
      into four groups: Control (C), fructose consumption (10%, F), NaCl consumption
      (salt 1% for the 10 last days, S), and fructose and NaCl (FS), and monitored for
      8 weeks. Metabolic evaluations consisted of Lee index, glycemia, insulin and
      glucose tolerance tests, triglycerides, and total cholesterol measurements.
      Cardiovascular parameters measured were arterial pressure (AP) and cardiac
      function performed by echocardiography. They also measured the influence of renin
      angiotensin (RAS) and autonomic nervous systems by drug blockage with losartan,
      atropine, and atenolol. RESULTS: Energy analysis showed no change between groups.
      Fructose overload induced a MS state, confirmed by insulin resistance, glucose
      intolerance, and dyslipidemia. Fasting glucose was increased in F and FS rat
      groups compared with C and S groups. AP was higher in F, S, and FS groups in
      comparison with the C group. The hypotensive response after sympathetic blockade
      was increased in F, S, and FS versus C. The cardiac vagal tonus was reduced in F
      and FS animal groups. The intrinsic heart rate was decreased in the FS group (372
      +/- 9 bpm) compared with the C group (410 +/- 13 bpm). The morphometric
      measurements evaluated through left ventricular diameter during diastole and the
      left ventricular diameter during systole decreased in the FS group (16 and 26%,
      respectively). Diastolic function was reduced in F and FS. The depressor response
      induced by losartan was increased in the F group in comparison with other groups.
      However, there was a uniform increase in plasma ACE activity in all treated
      groups compared with the C group. CONCLUSIONS: Data suggest that early exposure
      to high fructose intake produced marked alterations in metabolic and
      cardiovascular function. When stimulated by NaCl, the fructose-fed subjects
      showed further impairment in cardiac function.

PMID- 25564439
TI  - Measuring Work Functioning: Validity of a Weighted Composite Work Functioning
      Approach.
AB  - PURPOSE: To examine the construct validity of a weighted composite work
      functioning measurement approach. METHODS: Workers (health-impaired/healthy) (n =
      117) completed a composite measure survey that recorded four central work
      functioning aspects with existing scales: capacity to work, quality of work
      performance, quantity of work, and recovery from work. Previous derived weights
      reflecting the relative importance of these aspects of work functioning were used
      to calculate the composite weighted work functioning score of the workers. Work
      role functioning, productivity, and quality of life were used for validation.
      Correlations were calculated and norms applied to examine convergent and
      divergent construct validity. A t test was conducted and a norm applied to
      examine discriminative construct validity. RESULTS: Overall the weighted
      composite work functioning measure demonstrated construct validity. As predicted,
      the weighted composite score correlated (p < .001) strongly (r > .60) with work
      role functioning and productivity (convergent construct validity), and moderately
      (.30 < r < .60) with physical quality of life and less strongly than work role
      functioning and productivity with mental quality of life (divergent validity).
      Further, the weighted composite measure detected that health-impaired workers
      show with a large effect size (Cohen's d > .80) significantly worse work
      functioning than healthy workers (discriminative validity). CONCLUSION: The
      weighted composite work functioning measurement approach takes into account the
      relative importance of the different work functioning aspects and demonstrated
      good convergent, fair divergent, and good discriminative construct validity.

PMID- 25564437
TI  - Enhancing our understanding of anatomical diversity in Tomentella
      ectomycorrhizas: characterization of six new morphotypes.
AB  - Ectomycorrhizas (ECM) formed by Tomentella species (Thelephorales, Basidiomycota)
      were collected in beech forests of Hungary and studied using anatomical and
      molecular phylogenetic methods. The mycobionts were identified by analysing the
      sequences of nuclear ribosomal DNA (nrDNA) internal transcribed spacer (ITS)
      regions together with sequences obtained from public databases. At the sampling
      plots, we found the occurrence of 11 Tomentella morphotypes. Among these, six
      morphotypes (four identified, Tomentella atroarenicolor, Tomentella bryophila,
      Tomentella lapida, Tomentella subclavigera, and two unidentified) were morpho
      anatomically characterized for the first time. Although the six morphotypes
      differed anatomically from each other and from Tomentella ectomycorrhizas
      described previously, they shared anatomical features common to tomentelloid
      ectomycorrhizas fungi. These results expand our understanding of the diversity of
      this widely distributed ectomycorrhizal genus. 

PMID- 25564438
TI  - Up-regulation of genes involved in N-acetylglucosamine uptake and metabolism
      suggests a recycling mode of chitin in intraradical mycelium of arbuscular
      mycorrhizal fungi.
AB  - Arbuscular mycorrhizal (AM) fungi colonize roots and form two kinds of mycelium,
      intraradical mycelium (IRM) and extraradical mycelium (ERM). Arbuscules are
      characteristic IRM structures that highly branch within host cells in order to
      mediate resource exchange between the symbionts. They are ephemeral structures
      and at the end of their life span, arbuscular branches collapse from the tip,
      fungal cytoplasm withdraws, and the whole arbuscule shrinks into fungal clumps.
      The exoskeleton of an arbuscule contains structured chitin, which is a polymer of
      N-acetylglucosamine (GlcNAc), whereas a collapsed arbuscule does not. The
      molecular mechanisms underlying the turnover of chitin in AM fungi remain
      unknown. Here, a GlcNAc transporter, RiNGT, was identified from the AM fungus
      Rhizophagus irregularis. Yeast mutants defective in endogenous GlcNAc uptake and
      expressing RiNGT took up (14)C-GlcNAc, and the optimum uptake was at acidic pH
      values (pH 4.0-4.5). The transcript levels of RiNGT in IRM in mycorrhizal Lotus
      japonicus roots were over 1000 times higher than those in ERM. GlcNAc-6-phosphate
      deacetylase (DAC1) and glucosamine-6-phosphate isomerase (NAG1) genes, which are
      related to the GlcNAc catabolism pathway, were also induced in IRM. Altogether,
      data suggest the existence of an enhanced recycling mode of GlcNAc in IRM of AM
      fungi. 

PMID- 25564440
TI  - Validation of the Hsp70-Bag3 protein-protein interaction as a potential
      therapeutic target in cancer.
AB  - Hsp70 is a stress-inducible molecular chaperone that is required for cancer
      development at several steps. Targeting the active site of Hsp70 has proven
      relatively challenging, driving interest in alternative approaches. Hsp70
      collaborates with the Bcl2-associated athanogene 3 (Bag3) to promote cell
      survival through multiple pathways, including FoxM1. Therefore, inhibitors of the
      Hsp70-Bag3 protein-protein interaction (PPI) may provide a noncanonical way to
      target this chaperone. We report that JG-98, an allosteric inhibitor of this PPI,
      indeed has antiproliferative activity (EC50 values between 0.3 and 4 MUmol/L)
      across cancer cell lines from multiple origins. JG-98 destabilized FoxM1 and
      relieved suppression of downstream effectors, including p21 and p27. On the basis
      of these findings, JG-98 was evaluated in mice for pharmacokinetics,
      tolerability, and activity in two xenograft models. The results suggested that
      the Hsp70-Bag3 interaction may be a promising, new target for anticancer therapy.

PMID- 25564441
TI  - A Comprehensive Expression Analysis of Cancer Testis Antigens in Head and Neck
      Squamous Cell Carcinoma Revels MAGEA3/6 as a Marker for Recurrence.
AB  - Despite significant advances in the treatment of head and neck squamous cell
      carcinoma (HNSCC), the survival rate has not changed in the last decades.
      Therefore, the development of novel therapeutic strategies is pursued. Cancer
      testis antigens (CTA) are strong immunogenic proteins with a tumor-restricted
      expression pattern, and are considered ideal targets for tumor-specific
      immunotherapeutic approaches. In this study, using an in silico approach, we
      selected, among 139 previously described CTA, candidates to be evaluated in 89
      HNSCC and 20 normal mucosa samples. SPANX-CD (71.9%), MAGEB2 (44.9%), MAGEA1
      (44.9%), MAGEB6 (32.6%), and CXORF48 (27.0%) were found frequently expressed in
      HNSCC, and over 85% of the tumors expressed at least one of these five CTAs. The
      mRNA positivity of CXORF48, MAGEB6, and CRISP2 presented significant associations
      with recognized clinical features for poor outcome. Furthermore, MAGEA3/6
      positivity was associated with significantly better disease-free survival (DFS, P
      = 0.014), and the expression of this antigen was shown to be an independent
      prognostic factor for tumor recurrence. In conclusion, one of five selected CTAs
      is expressed in at least 85% of the HNSCCs, suggesting a possible usage as target
      for immunotherapeutic approaches, and the mRNA-positivity for MAGEA3/6 is shown
      to be an independent marker for DFS.

PMID- 25564442
TI  - Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac
      fate divergence.
AB  - Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in
      embryonic endothelium by unknown mechanisms. We discovered that Scl binds to
      hematopoietic and cardiac enhancers that become epigenetically primed in
      multipotent cardiovascular mesoderm, to regulate the divergence of hematopoietic
      and cardiac lineages. Scl does not act as a pioneer factor but rather exploits a
      pre-established epigenetic landscape. As the blood lineage emerges, Scl binding
      and active epigenetic modifications are sustained in hematopoietic enhancers,
      whereas cardiac enhancers are decommissioned by removal of active epigenetic
      marks. Our data suggest that, rather than recruiting corepressors to enhancers,
      Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors,
      such as Gata4 and Hand1, use for gene activation. Although hematopoietic Gata
      factors bind with Scl to both activated and repressed genes, they are dispensable
      for cardiac repression, but necessary for activating genes that enable
      hematopoietic stem/progenitor cell development. These results suggest that a
      unique subset of enhancers in lineage-specific genes that are accessible for
      regulators of opposing fates during the time of the fate decision provide a
      platform where the divergence of mutually exclusive fates is orchestrated.

PMID- 25564443
TI  - Mathematical model of the Tat-Rev regulation of HIV-1 replication in an activated
      cell predicts the existence of oscillatory dynamics in the synthesis of viral
      components.
AB  - BACKGROUND: The life cycle of human immunodeficiency virus type-1 (HIV-1) makes
      possible the realization of regulatory strategies that can lead to complex
      dynamical behavior of the system. We analyze the strategy which is based on two
      feedback mechanisms, one mediating a positive regulation of the virus replication
      by Tat protein via the antitermination of the genomic RNAs transcription on TAR
      (transactivation responsive) element of the proviral DNA and the second mechanism
      providing a negative regulation of the splicing of the full-length (9 kb) RNAs
      and incompletely spliced (4 kb) RNAs via their transport from the nucleus to the
      cytoplasm. Although the existence of these two regulatory feedback loops has been
      considered in other mathematical models, none of them examined the conditions for
      the emergence of complex oscillatory patterns in the intracellular dynamics of
      viral components. RESULTS: We developed a mechanistic mathematical model for the
      Tat-Rev mediated regulation of HIV-1 replication, which considers the activation
      of proviral DNA transcription, the Tat-specific antitermination of transcription
      on TAR-element, resulting in the synthesis of the full-length 9 kb RNA, the
      splicing of the 9 kb RNA down to the 4 kb RNA and the 4 kb RNA to 2 kb RNA, the
      transport of 2 kb mRNAs from the nucleus to the cytoplasm by the intracellular
      mechanisms, the multiple binding of the Rev protein to RRE (Rev Response Element)
      sites on 9 kb and 4 kb RNA resulting in their export to the cytoplasm and the
      synthesis of Tat and Rev proteins in the cytoplasm followed by their transport
      into the nucleus. The degradation of all viral proteins and RNAs both in the
      cytoplasm and the nucleus is described. The model parameters values were derived
      from the published literature data. The model was used to examine the dynamics of
      the synthesis of the viral proteins Tat and Rev, the mRNAs under the
      intracellular conditions specific for activated HIV-1 infected macrophages. In
      addition, we analyzed alternative hypotheses for the re-cycling of the Rev
      proteins both in the cytoplasm and the nuclear pore complex. CONCLUSIONS: The
      quantitative mathematical model of the Tat-Rev regulation of HIV-1 replication
      predicts the existence of oscillatory dynamics which depends on the efficacy of
      the Tat and TAR interaction as well as on the Rev-mediated transport processes.
      The biological relevance of the oscillatory regimes for the HIV-1 life cycle is
      discussed.

PMID- 25564445
TI  - Bone stock in revision femoral arthroplasty: a new evaluation.
AB  - PURPOSE: The purpose of this study was to finalize a method allowing a
      qualitative and numerical evaluation of the bone stock and to confirm its
      reproducibility, to verify the relationship between the secondary bone stock
      value and the functional results, and to determine the main factors influencing
      the value of the bone stock. METHODS: A clinical and radiological evaluation was
      performed in a group of 150 revisions of total hip replacements according to a
      new method taking into account cortical bone thickness, bone density and bone
      defects. RESULTS: Interobserver reproducibility was evaluated at an average of
      0.6 and intra-observer reproducibility was considered good at 0.8. Between the
      initial bone stock and at the last follow-up, no significant difference was
      noticed. For secondary bone stock considered as "very good or good", the gain was
      +38.1 points versus +29.9 points for patients evaluated as "average or poor" (p <
      0.0001). Between the initial bone stock assessment and at last follow-up, a
      significant relation was found in numerical values for the global type of primary
      fixation and in the presence of osteopenia (p < 0.0001). CONCLUSIONS: Deficient
      secondary bone stock can result in less favourable functional results. The
      numerical scores confirm the importance of strategic choices during surgery in
      order to manage bone stock preservation.

PMID- 25564446
TI  - Self-perceived barriers to eye care in a hard-to-reach population: the Karachi
      Marine Fishing Communities Eye and General Health Survey.
AB  - PURPOSE: We examined self-reported barriers to eye care among marginalized, hard
      to-reach fishing communities in Karachi, Pakistan. METHODS: The Karachi Marine
      Fishing Communities Eye and General Health Survey was a cross-sectional survey
      conducted between March 2009 and April 2010 in fishing communities in Keamari,
      Karachi, located on the coast of the Arabian Sea. Adults aged >=50 years living
      on seven islands and coastal areas were interviewed regarding sociodemographic
      background, experience of eye problems, eye care use, and barriers to access.
      They also were examined to determine visual acuity with a reduced logMAR chart
      and underwent a detailed eye examination. RESULTS: Of 700 people planned to be
      included in the study, 638 (91.1%) were interviewed and examined. Of these
      participants, 599 (93.9%) lived in extreme poverty and 84.3% had no school-based
      education, and 349 (54.7%; 95% confidence interval [CI], 50.8-58.6) of them had
      never had an eye examination. The common barriers to access identified included a
      perceived lack of or low need (176/349 or 50.4%), financial hardships (36.4%),
      "fears" (8.6%), and social support constraints (6.3%). Of those reporting a "lack
      of need," 21.9% had significant visual loss. Financial hardships, "fears," and
      social support constraints were more prevalent among women than men. Bengalis
      compared to Kutchis and Sindhis, and individuals with "poor/fragile" household
      financial status (self-reported) compared to those with "fine" status, were more
      likely to cite financial hardships. CONCLUSIONS: Access to eye care in this
      marginalized population is substantially hindered by perceived lack of need,
      financial hardships, and a range of "fears" and anxieties, despite a large unmet
      need. These barriers should be addressed while paying particular attention to
      gender, and ethnic and socioeconomic differences.

PMID- 25564444
TI  - Inhibition of quorum sensing in Pseudomonas aeruginosa by two herbal essential
      oils from Apiaceae family.
AB  - Ferula (Ferula asafoetida L.) and Dorema (Dorema aucheri Bioss.) both from
      Apiaceae family were tested for their anti-quorum sensing (QS) activity against
      Pseudomonas aeruginosa. Both essential oils exhibited anti-QS activity at 25
      MUg/ml of concenteration. At this concenteration Ferula fully abolished and
      Dorema reduced the violacein production by C. violaceum. Pyocyanin, pyoverdine,
      elastase and biofilm production were decreased in Ferula oil treatments. Dorema
      oil reduced pyoverdine and elastase production, while pyocyanin and biofilm
      production were not affacted. Expresion analysis of QS-dependent genes confirmed
      our phenotypic data. Our data introduced native Dorema and Ferula plants as novel
      QS and virulence inhibitors. 

PMID- 25564447
TI  - Brittle cornea syndrome ZNF469 mutation carrier phenotype and segregation
      analysis of rare ZNF469 variants in familial keratoconus.
AB  - PURPOSE: Brittle cornea syndrome 1 (BCS1) is a rare recessive condition
      characterized by extreme thinning of the cornea and sclera, caused by mutations
      in ZNF469. Keratoconus is a relatively common disease characterized by
      progressive thinning and ectasia of the cornea. The etiology of keratoconus is
      complex and not yet understood, but rare ZNF469 variants have recently been
      associated with disease. We investigated the phenotype of BCS1 carriers with
      known pathogenic ZNF469 mutations, and recruited families in which aggregation of
      keratoconus was observed to establish if rare variants in ZNF469 segregated with
      disease. METHODS: Patients and family members were recruited and underwent
      comprehensive anterior segment examination, including corneal topography. Blood
      samples were donated and genomic DNA was extracted. The coding sequence and
      splice sites of ZNF469 were PCR amplified and Sanger sequenced. RESULTS: Four
      carriers of three BCS1-associated ZNF469 loss-of-function mutations
      (p.[Glu1392Ter], p.[Gln1930Argfs*6], p.[Gln1930fs*133]) were examined and none
      had keratoconus. One carrier had partially penetrant features of BCS1, including
      joint hypermobility. ZNF469 sequencing in 11 keratoconus families identified 9
      rare (minor allele frequency [MAF] <= 0.025) variants predicted to be potentially
      damaging. However, in each instance the rare variant(s) identified, including two
      previously reported as potentially keratoconus-associated, did not segregate with
      the disease. CONCLUSIONS: The presence of heterozygous loss-of-function alleles
      in the ZNF469 gene did not cause keratoconus in the individuals examined. None of
      the rare nonsynonymous ZNF469 variants identified in the familial cohort
      conferred a high risk of keratoconus; therefore, genetic variants contributing to
      disease pathogenesis in these 11 families remain to be identified.

PMID- 25564449
TI  - Comparison of rates of change between binocular and monocular visual fields.
AB  - PURPOSE: To compare rates of change between binocular and monocular visual
      fields. METHODS: The study included 1264 visual fields from 62 normal-tension
      glaucoma patients with a minimum of nine pairs of visual fields for at least 5
      years of follow-up. Integrated binocular visual fields (BVFs) were calculated
      from the two monocular visual fields using a binocular summation. Linear
      regression of mean deviation (MD) values was used to evaluate the rates of change
      of the BVFs and monocular visual fields. For each patient, the eye with the worse
      MD value at baseline was defined as the worse MD eye. The eye with the faster
      rate of change of monocular visual fields was defined as the faster-changing eye.
      RESULTS: The mean age of subjects was 61.8 years at baseline, the mean number of
      paired visual field tests was 10.2, and the mean follow-up was 8.1 years. The
      mean rate of change in the BVFs (-0.10 dB/y) was significantly slower than that
      of the faster-changing eyes (-0.34 dB/y) and faster than that of the slower
      changing eyes (-0.06 dB/y; P < 0.001 for both comparisons). Forty-five eyes
      (64.5%) among the worse MD eyes at baseline were identified as faster-changing
      eyes at last follow-up, and having a worse MD value at baseline was a risk factor
      for being the faster-changing eye (P = 0.025). CONCLUSIONS: The rate of change in
      BVFs was intermediate between the rates of the faster-changing and slower
      changing eyes.

PMID- 25564448
TI  - Activation of TLR3 promotes the degeneration of retinal ganglion cells by
      upregulating the protein levels of JNK3.
AB  - PURPOSE: To investigate whether activation of Toll-like receptor 3 (TLR3)
      promotes the degeneration of retinal ganglion cells (RGCs) by upregulating the
      protein levels of c-jun N-terminal kinase 3 (JNK3). METHODS: Toll-like receptor 3
      specific activator, Poly(I:C) (polyinosinic-polycytidylic acid), or PBS was
      injected into the vitreous humor of Thy1-YFP mice. At 24, 48, and 72 hours after
      treatments, degeneration of RGCs was assessed by using antibodies against brain
      specific homeobox/POU domain protein 3a (Brn3a). A TLR3-specific inhibitor was
      injected into the vitreous humor with or without Poly(I:C). Western blot assays
      were performed to determine relative levels of TLR3, JNK3, pJNK3, and sterile
      alpha and HEAT/Armadillo motif-containing 1 (SARM1) proteins in retinal protein
      extracts, and immunohistochemistry assays were performed to determine their
      cellular localization in the retina. Mouse eyes were treated with Poly(I:C) or
      PBS along with MitoTracker Red, and colocalization of MitoTracker Red and JNK3 in
      the retinas was determined by using antibodies against JNK3. RESULTS: Poly(I:C)
      activated TLR3 and upregulated its downstream target protein JNK3 but not SARM1
      in the retina. Poly(I:C) activated TLR3 and upregulated JNK3 specifically in RGCs
      and promoted a significant degeneration of RGCs over a 72-hour time period. Toll
      like receptor 3 upregulated the levels of JNK3 protein in the cytoplasm of RGCs,
      but not in the mitochondria. Toll-like receptor 3-specific inhibitor
      downregulated Poly(I:C)-mediated upregulation of JNK3 protein, and, in turn,
      significantly attenuated TLR3-induced degeneration of RGCs. CONCLUSIONS: Results
      presented in this study show that the activation of TLR3 alone promotes the
      degeneration of RGCs by upregulating the protein levels of JNK3.

PMID- 25564450
TI  - Angiotensin II as a morphogenic cytokine stimulating fibrogenesis of human
      tenon's capsule fibroblasts.
AB  - PURPOSE: To examine the expression of Angiotensin II (Ang II) and its type I, and
      type II receptors (AT1R, AT2R) in rabbit Tenon's capsule fibroblasts after
      trabeculectomy, and to investigate the effects of Ang II on cultured human
      Tenon's capsule fibroblasts (HTFs) proliferation, migration, phenotype
      transition, and extracellular matrix (ECM) synthesis. METHODS: In the rabbit,
      expression of Ang II, AT1R, and AT2R in Tenon's capsule fibroblasts of eyes after
      trabeculectomy was evaluated by immunohistochemistry. Ang II levels in aqueous
      humor and plasma were assessed by ELISA. Cultured HTFs, obtained from patients
      undergoing cataract surgery, were treated with Ang II, TGF-beta1, or vehicle
      control. Cell proliferation and migration were evaluated by Cell Counting Kit-8
      and Transwell assay, and wound scratch assay, respectively. Protein expressions
      of alpha-smooth muscle actin (alpha-SMA) and fibronectin (FN) were measured by
      Western blot and immunofluorescence. Messenger RNA expressions of alpha-SMA and
      FN were measured by real-time PCR. RESULTS: In the rabbit, the expression of Ang
      II and AT1R increased from 1 day after surgery while AT2R increased from 7 days.
      In cultured HTFs, Ang II promoted cell proliferation and migration significantly
      (P < 0.05). Interestingly, the effect of 10(-7) M Ang II was more prominent than
      higher concentrations (10(-5) M; P < 0.05). Ang II also markedly induced the
      expression of alpha-SMA and FN, suggesting a phenotypic transition to
      myofibroblasts. CONCLUSIONS: Our results show that trabeculectomy alter the
      levels of Ang II and its receptors in Tenon's capsule fibroblasts, and that Ang
      II increase HTFs proliferation, migration, and phenotype transition, suggesting
      that Ang II may play a role in wound healing after trabeculectomy.

PMID- 25564451
TI  - Ultrastructure of adenovirus keratitis.
AB  - PURPOSE: We determined the ultrastructure of mouse adenovirus keratitis, a model
      for human adenovirus keratitis. METHODS: Adenovirus keratitis was induced in
      C57Bl/6j mice by intrastromal injection of human adenovirus species D type 37
      (HAdV-D37) with a heat-pulled, glass, micropipette needle under compressed air.
      At select time points after infection, mice were euthanized and their corneas
      removed, fixed, and sectioned at 70-nm thickness for electron microscopy.
      RESULTS: Injection of HAdV-D37 into the mouse corneal stroma placed virus
      predominantly in the pericellular corneal stromal matrix. Virus was seen bound to
      and entering stromal cells at 1 and 2 hours after infection, respectively. Cell
      membrane transit by virus was seen to involve two distinct structures resembling
      caveolae and macropinosomes. However, later during infection intracellular virus
      was not seen within membrane-bound organelles. By 8 hours after infection,
      intracellular virus had accumulated into densely packed, perinuclear arrays.
      Virus disassembly was not obvious at any time point after infection. Infiltrating
      neutrophils seen by one day after infection had engulfed degraded stromal cells
      by 4 days after infection. CONCLUSIONS: By transmission electron microscopy,
      injected HAdV-D37 readily enters stromal cells in the C57Bl/6j mouse cornea and
      induces stromal inflammation, as was shown previously by light microscopy.
      However, electron microscopy also revealed dense, static arrays of
      intracytoplasmic virus, suggesting a block in viral capsid disassembly and viral
      DNA nuclear entry. These findings may explain why human adenoviruses do not
      replicate in the mouse corneal stroma.

PMID- 25564453
TI  - The contrast sensitivity of the newborn human infant.
AB  - PURPOSE: To measure the binocular contrast sensitivity (CS) of newborn infants
      using a fixation-and-following card procedure. METHODS: The CS of 119 healthy
      newborn infants was measured using stimuli printed on cards under the descending
      method of limits (93 infants) and randomized/masked designs (26 infants). One
      experienced and one novice adult observer tested the infants using vertical
      square-wave gratings (0.06 and 0.10 cyc/deg; 20/10,000 and 20/6000 nominal
      Snellen equivalent); the experienced observer also tested using horizontal
      gratings (0.10 cyc/deg) and using the Method of Constant Stimuli while being kept
      unaware of the stimulus values. RESULTS: The CS of the newborn infant was 2.0
      (contrast threshold = 0.497; 95% confidence interval: 0.475-0.524) for vertically
      oriented gratings and 1.74 (threshold = 0.575; 95% confidence interval: 0.523
      0.633) for horizontally oriented gratings (P < 0.0006). The standard deviation of
      infant CS was comparable to that obtained by others on adults using the Pelli
      Robson chart. The two observers showed similar practice effects. Randomization of
      stimulus order and masking of the adult observer had no effect on CS.
      CONCLUSIONS: The CS of individual newborn human infants can be measured using a
      fixation-and-following card procedure.

PMID- 25564452
TI  - Fingerprinting of galectins in normal, P. aeruginosa-infected, and chemically
      burned mouse corneas.
AB  - PURPOSE: In this study, we aimed to assess whether the expression pattern of
      galectins is altered in Pseudomonas aeruginosa-infected and chemically burned
      mouse corneas. METHODS: Galectin (Gal) fingerprinting of normal, P. aeruginosa
      infected, and silver nitrate-cauterized corneas was performed by Western
      blotting, immunofluorescence staining, and qRT-PCR. RESULTS: In normal corneas,
      Gal-1 was distributed mainly in the stroma, Gal-3 was localized mainly in
      epithelium, and Gal-7, -8, and -9 were detected in both corneal epithelium and
      stroma. Expression levels of the five galectins were drastically altered under
      pathological conditions. In both infected and cauterized corneas, overall Gal-3
      expression was downregulated, whereas overall Gal-8 and -9 were upregulated.
      Changes in the expression level of Gal-7, -8, and -9 were distinct in the
      epithelium of infected and cauterized corneas. Expression of these three
      galectins was upregulated in corneal epithelium of infected corneas but not in
      cauterized corneas. Consistent with the changes in protein expression: (1) Gal-7,
      -8, and -9 mRNA expression was upregulated in cauterized corneas, and (2) Gal-3
      mRNA was downregulated and Gal-9 mRNA expression was upregulated in infected
      corneas. CONCLUSIONS: Our data demonstrate differential regulation of various
      members of the galectin family in the course of corneal infection and
      neovascularization. The emerging functionality of the sugar code of cell surface
      receptors via endogenous galectins reflect to the pertinent roles of the five
      tested galectins in the diseases of cornea.

PMID- 25564454
TI  - Care Management Medical Home Center Model: Preliminary Results of a Patient
      Centered Approach to Improving Care Quality for Diabetic Patients.
AB  - This article presents preliminary findings of the impact of an innovative care
      management model for diabetic patients. The model was implemented by seven
      Federally Qualified Health Centers serving 10,000 diabetic patients in Miami-Dade
      County. A primary intervention of this model is a centralized care management
      team that makes previsit phone calls to diabetic patients who have scheduled
      appointments. These previsit phone calls optimize patient knowledge and self
      management goals, and provide patient care coordinators with relevant clinical
      information to optimize the office visit and help to ensure completion of
      recommended diabetic preventive and chronic care services. Data suggest that
      following the implementation of this care management model, more diabetic
      patients are receiving regular care, and compliance with recommended tests and
      screenings has improved. 

PMID- 25564455
TI  - Role of the folate receptor in ovarian cancer treatment: evidence, mechanism, and
      clinical implications.
AB  - Folate can be transported into the cell by the reduced folate carrier (RFC), the
      proton-coupled folate transporter (PCFT), or the folate receptor (FR), of which
      various isoforms exist. While the RFC and PCFT are expressed by many normal
      cells, the FR is present only in a small proportion of normal tissues. In these
      tissues, the FR expression level is often low and restricted to the apical
      surface of polarized epithelial cells. In contrast, FR is expressed on the blood
      accessible basal and lateral membranes of many types of epithelial cancer.
      Considering that FR is expressed in few nonmalignant cell types on luminal
      membranes generally not accessible for molecules transported in the blood, FR is
      considered a promising antitumor target. As FR expression seems associated with
      tumor progression and prognosis, anticancer therapies targeting FR are currently
      being developed, such as farletuzumab (Morphotek, Exton, PA, USA), IMGN853
      (ImmunoGen, Waltham, MA, USA), vintafolide, and EC1456 (both Endocyte Inc., West
      Lafayette, IN, USA). FR expression could be used as a response-predictive
      biomarker for these treatments. The ability to identify patients and treat them
      with an effective therapy based on the known expression of the tumor marker
      would, indeed, be the next step in predictive medicine for these patients. This
      review summarizes the role of FR in ovarian cancer and the value of FR as a
      prognostic biomarker for ovarian cancer and a response-predictive biomarker for
      folate-targeted therapeutics. 

PMID- 25564456
TI  - Contribution of very late antigen-4 (VLA-4) integrin to cancer progression and
      metastasis.
AB  - The integrin "very late antigen-4" (VLA-4) is expressed by numerous cells of
      hematopoietic origin and possesses a key function in the cellular immune
      response, e.g., by mediating leukocyte tethering, rolling, binding, and finally
      transmigration of the vascular wall at inflammatory sites. Thus, VLA-4 is a
      valuable target in medical sciences to interfere with pathological inflammations.
      In addition, leukemic cells and different solid tumors, which express VLA-4, make
      use of these adhesive functions and confer VLA-4 a progressive role in the
      metastatic spread. With a growing insight into the molecular mechanisms for
      creating a tumor-friendly microenvironment at metastatic sites and various tumor
      host interactions, the multiple functions of VLA-4 became evident recently, e.g.,
      in leukocyte recruitment to micrometastases, the protection of tumors from immune
      surveillance, or contribution to a chemoresistance. Nevertheless, despite
      accumulating evidence for several functions of VLA-4 in tumorigenicity, a
      therapeutic interference with VLA-4 in cancer sciences has not been developed yet
      to the clinical level, undoubtedly by a marked impact on the physiological immune
      response. This review gives an up to date insight into the multiple functional
      role of VLA-4 in cancer and introduces this integrin as a promising target
      worthwhile to attract attention in biomedical cancer research. 

PMID- 25564457
TI  - The occurrence and progression of outer retinal tubulation in Chinese patients
      after intravitreal injections of ranibizumab.
AB  - To investigate the occurrence and progression of outer retinal tubulation (ORT)
      in Chinese patients after intravitreal ranibizumab injections, using spectral
      domain optical coherence tomography (SD-OCT) with eye tracking function. 15 age
      related macular degeneration (AMD) and 6 polypoidal choroidal vasculopathy (PCV)
      eyes of 21 patients were enrolled and assessed by SD-OCT. One patient received
      photodynamic therapy (PDT) previously, and all patients received intravitreal
      injections of ranibizumab. At baseline, only one AMD eye (4.8%) showed ORT, which
      appeared as round or ovoid hyporeflective spaces with hyperreflective borders.
      During the follow ups, ORT was identified in nine of 15 AMD eyes (60.0%) and one
      of six PCV eyes (16.7%). These new ORTs in 10 eyes were originated from the
      intraretinal fluid. Inner nuclear layer (INL), outer plexiform layer (OPL) and
      outer nuclear layer (ONL) were pulled down to form "cynapsis", separating each
      ORT. However, ORT in 3 eyes disappeared after intravitreal ranibizumab
      injections. This is the first observation on the occurrence and progression of
      ORT in Chinese AMD and PCV patients, in a point to point manner. The ORT could
      become stable or disappear after ranibizumab injections, and outer retina
      involved in the process of ORT formation. 

PMID- 25564459
TI  - beta-Blockers versus calcium channel blockers for acute rate control of atrial
      fibrillation with rapid ventricular response: a systematic review.
AB  - This is a systematic review of the literature to compare the efficacy of calcium
      channel blockers to beta-blockers for acute rate control of atrial fibrillation
      with rapid ventricular response in the emergency department setting. PubMed,
      EMBASE, and the Cochrane Registry were searched. Relative risk (95% confidence
      interval) was calculated between drugs and methodological quality of included
      studies was evaluated. Of the 1003 studies yielded by our initial search, two met
      inclusion criteria and provided sufficient data. These were randomized double
      blinded studies (n=92) comparing intravenous diltiazem with intravenous
      metoprolol. The combined relative risk of acute rate control by diltiazem versus
      metoprolol was 1.8 (95% confidence interval 1.2-2.6). On the basis of the paucity
      of available evidence, diltiazem may be more effective than metoprolol in
      achieving rapid rate control, but high-quality randomized studies are needed. 

PMID- 25564458
TI  - Reliability of electronic recording of waiting times in the emergency department:
      a prospective multicenter study.
AB  - We aimed to evaluate the reliability of waiting times (WT) measures
      electronically retrieved. We prospectively collected true WT in four emergency
      departments during 20 predefined 2-h inclusion periods, and compared them with
      the electronically retrieved waiting time (ERWT). We assessed agreement with
      calculation of rate of outliers (difference exceeding 20 min), bias, and its 95%
      limits of agreements, and associated Bland and Altman plot. We analyzed 274
      patients. The mean difference was -2 min (SD 13) between ERWT and true WT, with a
      95% limits of agreements (-28 to 24 min). Bland and Altman plot showed a good
      agreement, and we report 7% of outliers. Using ERWT, 14 patients (5%) were
      misclassified as having their target WT exceeded or not. ERWT agree well with the
      true WT, although the significant rate of outlier and misclassification calls for
      caution in their interpretation.

PMID- 25564460
TI  - Difference between how ambulance service personnel use paper and electronic
      patient care records when attending older people at home.

PMID- 25564461
TI  - Deep down on a Caribbean reef: lower mesophotic depths harbor a specialized coral
      endosymbiont community.
AB  - The composition, ecology and environmental conditions of mesophotic coral
      ecosystems near the lower limits of their bathymetric distributions remain poorly
      understood. Here we provide the first in-depth assessment of a lower mesophotic
      coral community (60-100 m) in the Southern Caribbean through visual submersible
      surveys, genotyping of coral host-endosymbiont assemblages, temperature
      monitoring and a growth experiment. The lower mesophotic zone harbored a
      specialized coral community consisting of predominantly Agaricia grahamae,
      Agaricia undata and a "deep-water" lineage of Madracis pharensis, with large
      colonies of these species observed close to their lower distribution limit of ~90
      m depth. All three species associated with "deep-specialist" photosynthetic
      endosymbionts (Symbiodinium). Fragments of A. grahamae exhibited growth rates at
      60 m similar to those observed for shallow Agaricia colonies (~2-3 cm yr(-1)),
      but showed bleaching and (partial) mortality when transplanted to 100 m. We
      propose that the strong reduction of temperature over depth (Delta5 degrees C
      from 40 to 100 m depth) may play an important contributing role in determining
      lower depth limits of mesophotic coral communities in this region. Rather than a
      marginal extension of the reef slope, the lower mesophotic represents a
      specialized community, and as such warrants specific consideration from science
      and management. 

PMID- 25564462
TI  - Translational downregulation of HSP90 expression by iron chelators in
      neuroblastoma cells.
AB  - Iron is an essential cellular nutrient, being a critical cofactor of several
      proteins involved in cell growth and replication. Compared with normal cells,
      neoplastic cells have been shown to require a greater amount of iron, thus laying
      the basis for the promising anticancer activity of iron chelators. In this work,
      we evaluated the effects of molecules with iron chelation activity on
      neuroblastoma (NB) cell lines. Of the 17 iron chelators tested, six reduced cell
      viability of two NB cell lines with an inhibition of growth of 50% below 10 uM;
      four of the six molecules-ciclopirox olamine (CPX), piroctone, 8
      hydroxyquinoline, and deferasirox-were also shown to efficiently chelate
      intracellular iron within minutes after addition. Effects on cell viability of
      one of the compounds, CPX, were indeed dependent on chelation of intracellular
      iron and mediated by both G0/G1 cell cycle block and induction of apoptosis. By
      combined transcriptome and translatome profiling we identified early
      translational downregulation of several members of the heat shock protein group
      as a specific effect of CPX treatment. We functionally confirmed iron-dependent
      depletion of HSP90 and its client proteins at pharmacologically achievable
      concentrations of CPX, and we extended this effect to piroctone, 8
      hydroxyquinoline, and deferasirox. Given the documented sensitivity of NB cells
      to HSP90 inhibition, we propose CPX and other iron chelators as investigational
      antitumor agents in NB therapy.

PMID- 25564463
TI  - On botulinum neurotoxin variability.
AB  - The rapidly growing number of botulinum neurotoxin sequences poses the problem of
      the possible evolutionary significance of the variability of these superpotent
      neurotoxins for toxin-producing Clostridium species. To progress in the
      understanding of this remarkable phenomenon, we suggest that researchers should
      (i) abandon an anthropocentric view of these neurotoxins as human botulism
      causing agents or as human therapeutics, (ii) begin to investigate in depth the
      role of botulinum neurotoxins in animal botulism in the wilderness, and (iii)
      devote large efforts to next-generation sequencing of soil samples to identify
      novel botulinum neurotoxins. In order to compare the fitness of the different
      toxins, we suggest that assays of all the steps from toxin production to animal
      death should be performed.

PMID- 25564464
TI  - Structural and molecular basis for resistance to aminoglycoside antibiotics by
      the adenylyltransferase ANT(2")-Ia.
AB  - The aminoglycosides are highly effective broad-spectrum antimicrobial agents.
      However, their efficacy is diminished due to enzyme-mediated covalent
      modification, which reduces affinity of the drug for the target ribosome. One of
      the most prevalent aminoglycoside resistance enzymes in Gram-negative pathogens
      is the adenylyltransferase ANT(2")-Ia, which confers resistance to gentamicin,
      tobramycin, and kanamycin. Despite the importance of this enzyme in drug
      resistance, its structure and molecular mechanism have been elusive. This study
      describes the structural and mechanistic basis for adenylylation of
      aminoglycosides by the ANT(2")-Ia enzyme. ANT(2")-Ia confers resistance by
      magnesium-dependent transfer of a nucleoside monophosphate (AMP) to the 2"
      hydroxyl of aminoglycoside substrates containing a 2-deoxystreptamine core. The
      catalyzed reaction follows a direct AMP transfer mechanism from ATP to the
      substrate antibiotic. Central to catalysis is the coordination of two Mg(2+)
      ions, positioning of the modifiable substrate ring, and the presence of a
      catalytic base (Asp86). Comparative structural analysis revealed that ANT(2")-Ia
      has a two-domain structure with an N-terminal active-site architecture that is
      conserved among other antibiotic nucleotidyltransferases, including Lnu(A), LinB,
      ANT(4')-Ia, ANT(4")-Ib, and ANT(6)-Ia. There is also similarity between the
      nucleotidyltransferase fold of ANT(2")-Ia and DNA polymerase beta. This
      similarity is consistent with evolution from a common ancestor, with the
      nucleotidyltransferase fold having adapted for activity against chemically
      distinct molecules. IMPORTANCE  : To successfully manage the threat associated
      with multidrug-resistant infectious diseases, innovative therapeutic strategies
      need to be developed. One such approach involves the enhancement or potentiation
      of existing antibiotics against resistant strains of bacteria. The reduction in
      clinical usefulness of the aminoglycosides is a particular problem among Gram
      negative human pathogens, since there are very few therapeutic options for
      infections caused by these organisms. In order to successfully circumvent or
      inhibit the activity of aminoglycoside-modifying enzymes, and to thus rejuvenate
      the activity of the aminoglycoside antibiotics against Gram-negative pathogens,
      structural and mechanistic information is crucial. This study reveals the
      structure of a clinically prevalent aminoglycoside resistance enzyme [ANT(2")-Ia]
      and depicts the molecular basis underlying modification of antibiotic substrates.
      Combined, these findings provide the groundwork for the development of broad
      spectrum inhibitors against antibiotic nucleotidyltransferases.

PMID- 25564465
TI  - Membrane anchoring of Epstein-Barr virus gp42 inhibits fusion with B cells even
      with increased flexibility allowed by engineered spacers.
AB  - We recently described the architecture of the Epstein-Barr virus (EBV) fusion
      triggering complex consisting of the EBV B cell receptor human leukocyte antigen
      (HLA) class II and the EBV-encoded proteins gp42 and gH/gL. The architecture of
      this structure positioned the main body of gp42, comprising the C-type lectin
      domain (CTLD), away from the membrane and distant from where the membrane-bound
      form of gp42 might be tethered. gp42 is a type II membrane glycoprotein, with
      functional gp42 formed by cleavage near the gp42 amino-terminal transmembrane
      domain. This cleavage results in an approximately 50-amino-acid unstructured
      region that is responsible for binding gH/gL with nanomolar affinity. Our
      previous studies had shown that membrane-bound gp42 is not functional in B cell
      fusion. To investigate whether we could restore gp42 function by extending it
      from the membrane, we introduced one, two, and four structured immunoglobulin
      like domains from muscle protein titin into a membrane-bound form of gp42 and
      tested function in binding to gHgL and HLA class II and function in fusion. We
      hypothesized that cleavage of gp42 generates a soluble functional form that
      relieves steric hindrance imposed on gHgL by membrane-bound gp42. All of the
      linker mutants had a dominant-negative effect on gp42 function, indicating that
      gp42 fusion function could not be restored simply by the addition of one to four
      titin domains. IMPORTANCE: Epstein-Barr virus (EBV) is associated with numerous
      diseases from benign mononucleosis to Burkitt's and Hodgkin's lymphoma,
      nasopharyngeal and gastric carcinoma, and lymphoproliferative disorders in
      patients with immune dysfunction resulting from immune suppression. Among the
      glycoproteins important for fusion, gp42, along with gH/gL, determines EBV
      tropism between epithelial and B cells. The function of gp42 is dependent on N
      terminal cleavage, since membrane-bound gp42 cannot mediate fusion. We further
      investigated whether insertion of a linker into membrane-bound gp42 would relieve
      steric hindrance imposed on membrane-bound gp42 and restore fusion function.
      However, adding one, two, or four structured immunoglobulin-like domains to
      membrane gp42 did not restore fusion activity, indicating that the architecture
      and membrane orientation of the B cell fusion-triggering complex of EBV may be
      easily perturbed and that gp42 cleavage is essential for B cell fusion.

PMID- 25564468
TI  - Isometric scaling of above- and below-ground biomass at the individual and
      community levels in the understorey of a sub-tropical forest.
AB  - BACKGROUND AND AIMS: Empirical studies and allometric partitioning (AP) theory
      indicate that plant above-ground biomass (MA) scales, on average, one-to-one
      (isometrically) with below-ground biomass (MR) at the level of individual trees
      and at the level of entire forest communities. However, the ability of the AP
      theory to predict the biomass allocation patterns of understorey plants has not
      been established because most previous empirical tests have focused on canopy
      tree species or very large shrubs. METHODS: In order to test the AP theory
      further, 1586 understorey sub-tropical forest plants from 30 sites in south-east
      China were harvested and examined. The numerical values of the scaling exponents
      and normalization constants (i.e. slopes and y-intercepts, respectively) of log
      log linear MA vs. MR relationships were determined for all individual plants, for
      each site, across the entire data set, and for data sorted into a total of 19 sub
      sets of forest types and successional stages. Similar comparisons of MA/MR were
      also made. KEY RESULTS: The data revealed that the mean MA/MR of understorey
      plants was 2.44 and 1.57 across all 1586 plants and for all communities,
      respectively, and MA scaled nearly isometrically with respect to MR, with scaling
      exponents of 1.01 for all individual plants and 0.99 for all communities. The
      scaling exponents did not differ significantly among different forest types or
      successional stages, but the normalization constants did, and were positively
      correlated with MA/MR and negatively correlated with scaling exponents across all
      1586 plants. CONCLUSIONS: The results support the AP theory's prediction that MA
      scales nearly one-to-one with MR (i.e. MA ? MR (~1.0)) and that plant biomass
      partitioning for individual plants and at the community level share a strikingly
      similar pattern, at least for the understorey plants examined in this study.
      Furthermore, variation in environmental conditions appears to affect the
      numerical values of normalization constants, but not the scaling exponents of the
      MA vs. MR relationship. This feature of the results suggests that plant size is
      the primary driver of the MA vs. MR biomass allocation pattern for understorey
      plants in sub-tropical forests.

PMID- 25564466
TI  - Protein A suppresses immune responses during Staphylococcus aureus bloodstream
      infection in guinea pigs.
AB  - Staphylococcus aureus infection is not associated with the development of
      protective immunity, and disease relapses occur frequently. We hypothesize that
      protein A, a factor that binds immunoglobulin Fcgamma and cross-links V(H)3 clan
      B cell receptors (IgM), is the staphylococcal determinant for host immune
      suppression. To test this, vertebrate IgM was examined for protein A cross
      linking. High V(H)3 binding activity occurred with human and guinea
      immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no
      binding, respectively. Establishing a guinea pig model of S. aureus bloodstream
      infection, we show that protein A functions as a virulence determinant and
      suppresses host B cell responses. Immunization with SpA(KKAA), which cannot bind
      immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to
      develop protective immunity. IMPORTANCE: Staphylococcus aureus is the leading
      cause of soft tissue and bloodstream infections; however, a vaccine with clinical
      efficacy is not available. Using mice to model staphylococcal infection, earlier
      work identified protective antigens; however, corresponding human clinical trials
      did not reach their endpoints. We show that B cell receptor (IgM) cross-linking
      by protein A is an important immune evasion strategy of S. aureus that can be
      monitored in a guinea pig model of bloodstream infection. Further, immunization
      with nontoxigenic protein A enables infected guinea pigs to elicit antibody
      responses that are protective against S. aureus. Thus, the guinea pig model may
      support preclinical development of staphylococcal vaccines.

PMID- 25564469
TI  - Simulating the germination response to diurnally alternating temperatures under
      climate change scenarios: comparative studies on Carex diandra seeds.
AB  - BACKGROUND AND AIMS: Environmental temperature regulates plant regeneration via
      seed in several superimposed ways, and this complex regulation will be disrupted
      by climate change. The role of diurnally alternating temperatures (DeltaT) in
      terminating dormancy will be a major factor in this disruption, as its effects on
      seed germination are immediate. METHODS: The effect of DeltaT on seed germination
      was modelled using two populations of the wetland sedge Carex diandra, one from a
      montane site and one from a subalpine site. A cardinal-temperature model was
      fitted to germination results obtained from a thermal gradient plate, and the
      model was used to simulate changes in germination under two possible future
      climate scenarios (RCP2.6 and RCP8.5, for representative concentration pathways)
      as defined by the Intergovernmental Panel on Climate Change. KEY RESULTS:
      Scenario RCP2.6 projected moderate increases in average temperatures and DeltaT,
      whereas RCP8.5 projected greater warming and higher DeltaT. Increasing DeltaT
      decreased the base temperature for seed germination and the thermal time required
      for germination. The effect of higher DeltaT together with the higher
      temperatures increased germination under both climate scenarios. CONCLUSIONS:
      Carex diandra germination is highly responsive to potential changes in DeltaT,
      and thus this study highlights the role of DeltaT in seed responses to climate
      change. Comprehensive cardinal-temperature models, encompassing the different
      effects of temperature on seed germination, are needed to understand how climate
      change will affect plant regeneration.

PMID- 25564467
TI  - Diversity, distribution and roles of osmoprotective compounds accumulated in
      halophytes under abiotic stress.
AB  - BACKGROUND AND AIMS: Osmolytes are low-molecular-weight organic solutes, a broad
      group that encompasses a variety of compounds such as amino acids, tertiary
      sulphonium and quaternary ammonium compounds, sugars and polyhydric alcohols.
      Osmolytes are accumulated in the cytoplasm of halophytic species in order to
      balance the osmotic potential of the Na(+) and Cl(-) accumulated in the vacuole.
      The advantages of the accumulation of osmolytes are that they keep the main
      physiological functions of the cell active, the induction of their biosynthesis
      is controlled by environmental cues, and they can be synthesized at all
      developmental stages. In addition to their role in osmoregulation, osmolytes have
      crucial functions in protecting subcellular structures and in scavenging reactive
      oxygen species. SCOPE: This review discusses the diversity of osmolytes among
      halophytes and their distribution within taxonomic groups, the intrinsic and
      extrinsic factors that influence their accumulation, and their role in
      osmoregulation and osmoprotection. Increasing the osmolyte content in plants is
      an interesting strategy to improve the growth and yield of crops upon exposure to
      salinity. Examples of transgenic plants as well as exogenous applications of some
      osmolytes are also discussed. Finally, the potential use of osmolytes in protein
      stabilization and solvation in biotechnology, including the pharmaceutical
      industry and medicine, are considered.

PMID- 25564470
TI  - Differential pathways of positive and negative health behavior change in
      congestive heart failure patients.
AB  - This longitudinal study applied a stress and coping model to examine the
      differential pathways of perceived positive and negative health behavior changes.
      Participants with congestive heart failure completed self-report measures of
      psychological resources, coping strategies, and perceived behavior changes and
      were assessed again 6 months later. Patients with higher positive affect and
      spiritual well-being reported more positive health behavior changes over time,
      effects mediated by approach coping. Alternatively, patients with lower
      psychological resources reported more negative behavior changes over time,
      effects mediated by avoidance coping. The results suggest that different
      psychological resources are related to different types of coping which, in turn,
      are associated with perceived positive or negative changes in health behavior
      over time.

PMID- 25564471
TI  - Career identity in the veterinary profession.
AB  - This research investigates vet and vet nurse career identity through the
      qualitative methodology of narrative enquiry. It derives learning and
      understanding from these empirical data to assist the veterinary profession to
      adjust to the changing industry landscape. Through a case series of 20 vets and
      vet nurses' career stories, this paper seeks understanding about career identity
      and its impact on individuals and organisations in the light of industry
      consolidation. Findings suggest that career is central to identity for many
      veterinary professionals who tend to have a strong sense of self; this is
      particularly evident around self as learner and technically competent, teacher
      and educator, ethical and moral and dedicated and resilient. Consequently,
      mismatches between 'who I am' and 'what I do' tend not to lead to identity
      customisation (to fit self into role or organisation) but to the search for
      alternative, more identity-compatible employment. This study offers a valuable
      insight for employers, veterinary professionals and universities. It suggests
      that businesses can gain competitive advantage and employees achieve validation
      and enrichment by working towards organisational and individual identity
      congruence and that teaching veterinary professionals with contemporary business
      in mind may develop graduates with a more sustainable identity. 

PMID- 25564472
TI  - Investigating common clinical presentations in first opinion small animal
      consultations using direct observation.
AB  - Understanding more about the clinical presentations encountered in veterinary
      practice is vital in directing research towards areas relevant to practitioners.
      The aim of this study was to describe all problems discussed during a convenience
      sample of consultations using a direct observation method. A data collection tool
      was used to gather data by direct observation during small animal consultations
      at eight sentinel practices. Data were recorded for all presenting and non
      presenting specific health problems discussed. A total of 1901 patients were
      presented with 3206 specific health problems discussed. Clinical presentation
      varied widely between species and between presenting and non-presenting problems.
      Skin lump, vomiting and inappetence were the most common clinical signs reported
      by the owner while overweight/obese, dental tartar and skin lump were the most
      common clinical examination findings. Skin was the most frequently affected body
      system overall followed by non-specific problems then the gastrointestinal
      system. Consultations are complex, with a diverse range of different clinical
      presentations seen. Considering the presenting problem only may give an
      inaccurate view of the veterinary caseload, as some common problems are rarely
      the reason for presentation. Understanding the common diagnoses made is the next
      step and will help to further focus questions for future research. 

PMID- 25564473
TI  - Responses to successive anti-epileptic drugs in canine idiopathic epilepsy.

PMID- 25564475
TI  - Modulation of glucose metabolism by the renin-angiotensin-aldosterone system.
AB  - The renin-angiotensin-aldosterone system (RAAS) is an enzymatic cascade
      functioning in a paracrine and autocrine fashion. In animals and humans, RAAS
      intrinsic to tissues modulates food intake, metabolic rate, adiposity, insulin
      sensitivity, and insulin secretion. A large array of observations shows that
      dysregulation of RAAS in the metabolic syndrome favors type 2 diabetes.
      Remarkably, angiotensin-converting enzyme inhibitors, suppressing the synthesis
      of angiotensin II (ANG II), and angiotensin receptor blockers, targeting the ANG
      II type 1 receptor, prevent diabetes in patients with hypertensive or ischemic
      cardiopathy. These drugs interrupt the negative feedback loop of ANG II on the
      RAAS cascade, which results in increased production of angiotensins. In addition,
      they change the tissue expression of RAAS components. Therefore, the concept of a
      dual axis of RAAS regarding glucose homeostasis has emerged. The RAAS deleterious
      axis increases the production of inflammatory cytokines and raises oxidative
      stress, exacerbating the insulin resistance and decreasing insulin secretion. The
      beneficial axis promotes adipogenesis, blocks the production of inflammatory
      cytokines, and lowers oxidative stress, thereby improving insulin sensitivity and
      secretion. Currently, drugs targeting RAAS are not given for the purpose of
      preventing diabetes in humans. However, we anticipate that in the near future the
      discovery of novel means to modulate the RAAS beneficial axis will result in a
      decisive therapeutic breakthrough. 

PMID- 25564474
TI  - Cyclin C stimulates beta-cell proliferation in rat and human pancreatic beta
      cells.
AB  - Activation of pancreatic beta-cell proliferation has been proposed as an approach
      to replace reduced functional beta-cell mass in diabetes. Quiescent fibroblasts
      exit from G0 (quiescence) to G1 through pRb phosphorylation mediated by cyclin
      C/cdk3 complexes. Overexpression of cyclin D1, D2, D3, or cyclin E induces
      pancreatic beta-cell proliferation. We hypothesized that cyclin C overexpression
      would induce beta-cell proliferation through G0 exit, thus being a potential
      therapeutic target to recover functional beta-cell mass. We used isolated rat and
      human islets transduced with adenovirus expressing cyclin C. We measured multiple
      markers of proliferation: [(3)H]thymidine incorporation, BrdU incorporation and
      staining, and Ki67 staining. Furthermore, we detected beta-cell death by TUNEL,
      beta-cell differentiation by RT-PCR, and beta-cell function by glucose-stimulated
      insulin secretion. Interestingly, we have found that cyclin C increases rat and
      human beta-cell proliferation. This augmented proliferation did not induce beta
      cell death, dedifferentiation, or dysfunction in rat or human islets. Our results
      indicate that cyclin C is a potential target for inducing beta-cell regeneration.

PMID- 25564476
TI  - Direct effect of incretin hormones on glucose and glycerol metabolism and
      hemodynamics.
AB  - The objective of this study was to assess the insulin-independent effects of
      incretin hormones on glucose and glycerol metabolism and hemodynamics under
      euglycemic and hyperglycemic conditions. Young, healthy men (n=10) underwent
      three trials in a randomized, controlled, crossover study. Each trial consisted
      of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using
      somatostatin to prevent endogenous insulin secretion). Glucose and lipid
      metabolism was measured via infusion of stable glucose and glycerol isotopic
      tracers. Hemodynamic variables (femoral, brachial, and common carotid artery
      blood flow and flow-mediated dilation of the brachial artery) were also measured.
      The three trials differed as follows: 1) saline [control (CON)], 2) glucagon-like
      peptide (GLP-1, 0.5 pmol.kg(-1).min(-1)), and 3) glucose-dependent insulinotropic
      polypeptide (GIP, 1.5 pmol.kg(-1).min(-1)). No between-trial differences in
      glucose infusion rates (GIR) or glucose or glycerol kinetics were seen during
      euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of
      disappearance during GLP-1 compared with CON and GIP (P<0.01 for all). However,
      when normalized to insulin levels, no differences between trials were seen for
      GIR or glucose rate of disappearance. Besides a higher femoral blood flow during
      hyperglycemia with GIP (vs. CON and GLP-1, P<0.001), no between-trial differences
      were seen for the hemodynamic variables. In conclusion, GLP-1 and GIP have no
      direct effect on whole body glucose metabolism or hemodynamics during euglycemia.
      On the contrary, during hyperglycemia, GIP increases femoral artery blood flow
      with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal,
      potentially due to increased insulin levels.

PMID- 25564478
TI  - Abdominal pain: a diagnostic challenge. Pseudo-obstruction.

PMID- 25564479
TI  - Alcohol use and misuse, self-harm and subsequent mortality: an epidemiological
      and longitudinal study from the multicentre study of self-harm in England.
AB  - OBJECTIVES: Alcohol use and misuse are strongly associated with self-harm and
      increased risk of future self-harm and suicide. The UK general population
      prevalence of alcohol use, misuse and alcohol-attributable harm has been rising.
      We have investigated the prevalence of and trends in alcohol use and misuse in
      self-harm patients and their associations with repeat self-harm and subsequent
      death. METHODS: We used patient data from the Multicentre Study of Self-Harm in
      England for 2000-2009 and UK mortality data for patients presenting from 2000 to
      2007 who were followed up to the end of 2009. RESULTS: Alcohol involvement in
      acts of self-harm (58.4%) and alcohol misuse (36.1%) were somewhat higher than
      found previously in self-harm patients. Alcohol involvement and misuse were most
      frequent in men, those aged 35-54 years and those from white ethnicities. The
      frequency of alcohol misuse increased between 2000 and 2009, especially in women.
      Repetition of self-harm was associated with alcohol involvement in self-harm and
      particularly with alcohol misuse. Risk of suicide was increased significantly in
      women misusing alcohol. CONCLUSIONS: Alcohol use and misuse in self-harm patients
      appears to have increased in recent years, particularly in women. The association
      of alcohol with greater risk of self-harm repetition and mortality highlights the
      need for clinicians to investigate alcohol use in self-harm patients. Ready
      availability of alcohol treatment staff in general hospitals could facilitate
      appropriate aftercare and the prevention of adverse outcomes.

PMID- 25564477
TI  - P65 inactivation in adipocytes and macrophages attenuates adipose inflammatory
      response in lean but not in obese mice.
AB  - NF-kappaB induces transcriptional expression of proinflammatory genes and
      antiapoptotic genes. The two activities of NF-kappaB remain to be characterized
      in the mechanism of chronic inflammation in obesity. To address this issue, we
      inactivated NF-kappaB in adipose tissue by knocking out p65 (RelA) in mice (F-p65
      KO) and examined the inflammation in lean and obese conditions. In the lean
      condition, KO mice exhibited a reduced inflammation in adipose tissue with a
      decrease in macrophage infiltration, M1 polarization, and proinflammatory
      cytokine expression. In the obese condition, KO mice had elevated inflammation
      with more macrophage infiltration, M1 polarization, and cytokine expression. In
      the mechanism of enhanced inflammation, adipocytes and macrophages exhibited an
      increase in cellular apoptosis, which was observed with more formation of crown
      like structures (CLS) in fat tissue of KO mice. Body weight, glucose metabolism,
      and insulin sensitivity were not significantly altered in KO mice under the lean
      and obese conditions. A modest but significant reduction in body fat mass was
      observed in KO mice on HFD with an elevation in energy expenditure. The data
      suggest that in the control of adipose inflammation, NF-kappaB exhibits different
      activities in the lean vs. obese condition. NF-kappaB is required for expression
      of proinflammatory genes in the lean but not in the obese condition. NF-kappaB is
      required for inhibition of apoptosis in the obese condition, in which
      proinflammation is enhanced by NF-kappaB inactivation. 

PMID- 25564480
TI  - Choreographing lived experience: dance, feelings and the storytelling body.
AB  - Although narrative-based research has been central to studies of illness
      experience, the inarticulate, sensory experiences of illness often remain
      obscured by exclusively verbal or textual inquiry. To foreground the body in our
      investigation of subjective and intersubjective aspects of eating disorders, we-a
      medical anthropologist and a contemporary dance choreographer-designed a
      collaborative project, in which we studied the experiences of women who had
      eating disorders, through eight weeks of integrating dance practice-based,
      discussion-based and interview-based research. Grounded in the participants' own
      reflections on choreographing, dancing and watching others perform solos about
      their eating disordered experiences, our analysis examines the types of knowledge
      the participants used in choreographing their dance works, and the knowledge that
      they felt the dance enabled them to convey. We find that the participants
      consistently spoke of feeling as guiding their choreographic processes; they also
      said the experiences they conveyed through their dance works were centred in
      feelings, rather than in practices or events. Through dance, the participants
      said they could communicate experiences that would have remained unspoken
      otherwise. Yet, notably, dance practice also enabled participants to begin
      defining and describing their experiences verbally. We suggest, therefore, that
      through engaging participants in contemporary dance practice, we can begin to
      identify and address embodied experiences of illness and recovery that may be
      silenced in speech or writing alone. 

PMID- 25564481
TI  - Early Posttraumatic Seizures in the Pediatric Population.
AB  - Early posttraumatic seizure is a paramount clinical issue in pediatric traumatic
      brain injury patients as it is a common occurrence, yet an understudied entity at
      present. Recent literature recognizes several posttraumatic seizure subtypes
      based on time of presentation and the underlying pathophysiology: impact,
      immediate, delayed early, and late/posttraumatic epilepsy. Appropriate
      classification of pediatric posttraumatic seizure subtypes can be helpful for
      appropriate management and prognosis. This review will focus on early
      posttraumatic seizures, and the subtypes of early posttraumatic seizure.
      Incidence, risk factors, diagnosis, seizure semiology, status epilepticus,
      management, risk of recurrence, and prognosis were reviewed. The integration of
      continuous electroencephalographic (EEG) monitoring into pediatric traumatic
      brain injury management may hold the key to better characterizing and
      understanding pediatric early posttraumatic seizures. Topics for future research
      pertaining to pediatric early posttraumatic seizure are identified. 

PMID- 25564482
TI  - How Physicians Support Mothers of Children with Duchenne Muscular Dystrophy.
AB  - Communicating about Duchenne muscular dystrophy and its prognosis can be
      difficult for affected children and their family. We focused on how physicians
      provide support to the mothers of children with Duchenne muscular dystrophy who
      have difficulty communicating about the condition with their child. The eligible
      participants were certified child neurologists of the Japanese Society of Child
      Neurology. Participants responded to questionnaires consisting of free
      descriptions of a vignette of a child with Duchenne muscular dystrophy and a
      mother. We analyzed 263 responses of the participants. We found 4 themes on
      advising mothers, involving encouraging communication, family autonomy,
      supporting family, and considering the child's concerns. These results provide a
      better understanding of the communication between physicians and family members
      who need help sharing information with a child with Duchenne muscular dystrophy.
      These findings will assist clinical practitioners in supporting families and the
      affected children throughout the course of their illness. 

PMID- 25564484
TI  - Rare complication of silicone fluid injection presenting as multiple
      calcification and skin defect in both legs: a case report.
AB  - In the past, many materials have been injected for soft tissue augmentation
      including paraffin (mineral oil) and other non-biocompatible products. Liquid
      silicone as one of these materials has a long and notorious history as an
      injectable material for soft tissue augmentation. However, complications,
      including cellulitis, ulcerations, migration, and nodule formation, have also
      been reported with silicone injections. This article aims to demonstrate the
      diagnosis and treatment of multiple calcification and skin defect after silicone
      fluid injection for soft tissue augmentation. A 65-year-old female presented with
      skin defect and calcifications had been steadily increasing in size over a 3
      month period. Examination confirmed pain, swelling, induration, and 5 * 5 cm
      sized skin defect with marginal and adjacent calcification in the left lateral
      malleolar area. She had been injected silicone fluid for soft tissue of lower
      extremity augmentation and contouring 30 years ago. Serial surgical debridement
      of this entire zone of calcification and ulceration was undertaken. The defect
      was closed by a split thickness skin graft. She was satisfied with the aesthetic
      appearance of the lateral malleolar area, relieving the symptoms of cellulitis. 

PMID- 25564483
TI  - Diagnostic Clues to Human Herpesvirus 6 Encephalitis and Wernicke Encephalopathy
      After Pediatric Hematopoietic Cell Transplantation.
AB  - Human herpesvirus 6 (HHV6) encephalitis and Wernicke encephalopathy are treatable
      yet frequently undiagnosed causes of encephalopathy in pediatric recipients of
      allogeneic and autologous hematopoietic cell transplantation. Here we review
      representative cases of both conditions to highlight specific and relevant
      neurologic features that prompted effective diagnosis and treatment. Two patients
      with confusion accompanied by seizures, memory changes, or specific visual
      hallucinations and HHV6 detectable by polymerase chain reaction (PCR) in
      cerebrospinal fluid had improvement in viral load with ganciclovir or foscarnet
      treatment. Two patients had confusion, ataxia, or ocular changes and low serum
      thiamine levels, which resolved with parenteral thiamine. In all cases,
      definitive diagnosis and treatment were facilitated by a high index of suspicion
      and search for specific pathognomonic neurologic deficits accompanying the
      confusional state. It is critical to clinically differentiate these 2 conditions
      from other common neurologic syndromes occurring after transplant, allowing
      potentially improved patient outcomes by prompt diagnosis and effective
      treatment. 

PMID- 25564485
TI  - Calpains mediate the proteolytic modification of human cytomegalovirus UL112-113
      proteins.
AB  - The human cytomegalovirus (HCMV) UL112-113 gene is implicated in lytic viral
      replication. The UL112-113 proteins p34, p43, p50 and p84 are expressed via
      alternative splicing. However, the mechanism for the generation of three
      additional virus-associated proteins (p20, p26 and p28), which share the UL112
      reading frame, remains unknown. Bioinformatic analyses indicated that p34, p43,
      p50 and p84 contain potential PEST-like degradation motifs. In this study,
      inhibitors of calpains, lysosomes and proteasomes reduced p20, p26 and p28 levels
      in virus-infected cells, suggesting the involvement of proteolytic modification.
      Moreover, maitotoxin, which increases intracellular calcium levels and activates
      calpain activity, induced the intracellular proteolysis of p34 into p20, p26 and
      p28 and the cleavage of p43, p50 and p84 into p38 and a novel protein, p34c.
      Proteolytic assays further indicated that p34, p43, p50 and p84 were substrates
      of calpain-1 and calpain-2 and that they generated proteolytic products that
      corresponded to those detected during the HCMV infectious period. Furthermore,
      substitution mutations in the putative calpain cleavage sites of p34 reduced
      accumulation of proteolytic products. The knockdown of endogenous calpain-1 and
      calpain-2 by RNA interference reduced accumulation of p20, p26 and p28 and
      concurrently increased levels of nascent p43, p50 and p84 during the infectious
      cycle. Intriguingly, calpain depletion enhanced viral genome synthesis. Moreover,
      HCMV-permissive cells that stably expressed p20, p26 or p28 exhibited reduced
      viral genome synthesis and mature virus production. Our findings suggest that
      cognate UL112-113 proteins derived from calpain-catalysed proteolysis are
      involved in the HCMV replication process.

PMID- 25564486
TI  - Thermal characterization of static and dynamical properties of the confined
      molecular systems interacting through dispersion force.
AB  - We investigated the thermal properties of liquid methylcyclohexane and racemic
      sec-butylcyclohexane, as representatives of a molecular system with only
      dispersion-force intermolecular interactions, confined in the pores
      (thickness/diameter d = 12, 6, 1.1 nm) of silica gels by adiabatic calorimetry.
      The results imply a heterogeneous picture for molecular aggregate under
      confinement consisting of an interfacial region and an inner pore one. In the
      vicinity of a glass-transition temperature T(g,bulk) of bulk liquid, two
      distinguishable relaxation phenomena were observed for the confined systems and
      their origins were attributed to the devitrification, namely glass transition,
      processes of (1) a layer of interfacial molecules adjacent to the pore walls and
      (2) the molecules located in the middle of the pore. A third glass-transition
      phenomenon was observed at lower temperatures and ascribed to a secondary
      relaxation process. The glass transition of the interfacial-layer molecules was
      found to proceed at temperatures rather above T(g,bulk), whereas that of the
      molecules located in the inner pore region occurred at temperatures below
      T(g,bulk). We discuss the reason why the molecules located in different places in
      the pores reveal the respectively different dynamical properties.

PMID- 25564487
TI  - Editorial.

PMID- 25564488
TI  - Treatment-induced neuropathy of diabetes: an energy crisis?

PMID- 25564489
TI  - A mouse model of autoimmune encephalitis.

PMID- 25564490
TI  - A new TRAIL in Alzheimer's disease therapy.

PMID- 25564491
TI  - Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging.
AB  - The original concept of the ischaemic penumbra suggested imaging of regional
      cerebral blood flow and metabolism would be required to identify tissue that may
      benefit from intervention. Amide proton transfer magnetic resonance imaging, a
      chemical exchange saturation transfer technique, has been used to derive cerebral
      intracellular pH in preclinical stroke models and has been proposed as a
      metabolic marker of ischaemic penumbra. In this proof of principle clinical
      study, we explored the potential of this pH-weighted magnetic resonance imaging
      technique at tissue-level. Detailed voxel-wise analysis was performed on data
      from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels
      within ischaemic core had a more severe intracellular acidosis than hypoperfused
      tissue recruited to the final infarct (P < 0.0001), which in turn was more
      acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when
      confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but
      not cerebral blood flow (P = 0.31), differed between tissue that infarcted and
      tissue that survived. Within the presenting apparent diffusion coefficient
      lesion, intracellular pH differed between tissue with early apparent diffusion
      lesion pseudonormalization and tissue with true radiographic recovery. These
      findings support the need for further investigation of pH-weighted imaging in
      patients with acute ischaemic stroke. 

PMID- 25564493
TI  - Mapping longitudinal studies to risk factors in an ontology for dementia.
AB  - A common activity carried out by healthcare professionals is to test various
      hypotheses on longitudinal study data in an effort to develop new and more
      reliable algorithms that might determine the possibility of developing certain
      illnesses. The INnovative, Midlife INtervention for Dementia Deterrence project
      provides input from a number of European dementia experts to identify the most
      accurate model of inter-related risk factors which can yield a personalized
      dementia-risk quotient and profile. This model is then validated against the
      large population-based prospective Maastricht Aging Study dataset. As part of
      this overall goal, the research presented in this article demonstrates how we can
      automate the process of mapping modifiable risk factors against large sections of
      the aging study and thus use information technology to provide more powerful
      query interfaces.

PMID- 25564494
TI  - The value of telehealth in the early detection of chronic obstructive pulmonary
      disease exacerbations: A prospective observational study.
AB  - We aim to establish the value of telemonitoring in the early detection of chronic
      obstructive pulmonary disease exacerbations. We followed up patients undergoing
      chronic obstructive pulmonary disease telemonitoring for 4 months. We studied
      changes in the telemonitored data in the week prior to admission or to community
      chronic obstructive pulmonary disease exacerbation. A total of 183 patients were
      studied. In all, 30 chronic obstructive pulmonary disease-related hospital
      admissions and 68 chronic obstructive pulmonary disease community exacerbations
      were recorded. Changes in telehealth parameters occurred in 80 per cent (24/30)
      of admissions and 82 per cent (56/68) of community exacerbations. Although
      changes in telehealth data occurred in the majority of exacerbations, most
      individual symptoms was present in less than half the exacerbations and almost 20
      per cent of exacerbations were not preceded by any change in telemonitoring data.
      Cough created significantly more alerts by those treated in the community (p =
      0.008), whereas a drop in oxygen saturation created significantly more alerts pre
      hospitalisation (p = 0.049). We conclude that further work is required to develop
      methods of identifying impending chronic obstructive pulmonary disease
      exacerbations with greater sensitivity and specificity.

PMID- 25564495
TI  - Sub-diffusive electronic transport in a DNA single-strand chain with electron
      phonon coupling.
AB  - We investigate the electronic wavepacket dynamics in a finite segment of a DNA
      single-strand chain considering the electron-phonon coupling. Our theoretical
      approach makes use of an effective tight-binding Hamiltonian to describe the
      electron dynamics, together with a classical harmonic Hamiltonian to treat the
      intrinsic DNA vibrations. An effective time-dependent Schrodinger equation is
      then settled up and solved numerically for an initially localized wave-packet
      using the standard Dormand-Prince eighth-order Runge-Kutta method. Our numerical
      results indicate the presence of a sub-diffusive electronic wavepacket spread
      mediated by the electron-phonon interaction. 

PMID- 25564496
TI  - Tunable valley polarization by a gate voltage when an electron tunnels through
      multiple line defects in graphene.
AB  - By means of an appropriate wave function connection condition, we study the
      electronic structure of a line defect superlattice of graphene with the Dirac
      equation method. We obtain the analytical dispersion relation, which can simulate
      well the tight-binding numerical result about the band structure of the
      superlattice. Then, we generalize this theoretical method to study the electronic
      transmission through a potential barrier where multiple line defects are
      periodically patterned. We find that there exists a critical incident angle which
      restricts the electronic transmission through multiple line defects within a
      specific incident angle range. The critical angle depends sensitively on the
      potential barrier height, which can be modulated by a gate voltage. As a result,
      non-trivial transmissions of K and K' valley electrons are restricted,
      respectively, in two distinct ranges of the incident angle. Our theoretical
      result demonstrates that a gate voltage can act as a feasible measure to tune the
      valley polarization when electrons tunnel through multiple line defects. 

PMID- 25564492
TI  - Gain of Olig2 function in oligodendrocyte progenitors promotes remyelination.
AB  - The basic helix-loop-helix transcription factor Olig2 is a key determinant for
      the specification of neural precursor cells into oligodendrocyte progenitor
      cells. However, the functional role of Olig2 in oligodendrocyte migration and
      differentiation remains elusive both during developmental myelination and under
      demyelinating conditions of the adult central nervous system. To decipher Olig2
      functions, we generated transgenic mice (TetOlig2:Sox10(rtTA/+)) overexpressing
      Olig2 in Sox10(+) oligodendroglial cells in a doxycycline inducible manner. We
      show that Olig2 overexpression increases the generation of differentiated
      oligodendrocytes, leading to precocious myelination of the central nervous
      system. Unexpectedly, we found that gain of Olig2 function in oligodendrocyte
      progenitor cells enhances their migration rate. To determine whether Olig2
      overexpression in adult oligodendrocyte progenitor cells promotes oligodendrocyte
      regeneration for myelin repair, we induced lysophosphatidylcholine demyelination
      in the corpus callosum of TetOlig2:Sox10(rtTA/+) and control mice. We found that
      Olig2 overexpression enhanced oligodendrocyte progenitor cell differentiation and
      remyelination. To assess the relevance of these findings in demyelinating
      diseases, we also examined OLIG2 expression in multiple sclerosis lesions. We
      demonstrate that OLIG2 displays a differential expression pattern in multiple
      sclerosis lesions that correlates with lesion activity. Strikingly, OLIG2 was
      predominantly detected in NOGO-A(+) (now known as RTN4-A) maturing
      oligodendrocytes, which prevailed in active lesion borders, rather than chronic
      silent and shadow plaques. Taken together, our data provide proof of principle
      indicating that OLIG2 overexpression in oligodendrocyte progenitor cells might be
      a possible therapeutic mechanism for enhancing myelin repair. 

PMID- 25564497
TI  - Two Lactococcus lactis thioredoxin paralogues play different roles in responses
      to arsenate and oxidative stress.
AB  - Thioredoxin (Trx) maintains intracellular thiol groups in a reduced state and is
      involved in a wide range of cellular processes, including ribonucleotide
      reduction, sulphur assimilation, oxidative stress responses and arsenate
      detoxification. The industrially important lactic acid bacterium Lactococcus
      lactis contains two Trxs. TrxA is similar to the well-characterized Trx homologue
      from Escherichia coli and contains the common WCGPC active site motif, while TrxD
      is atypical and contains an aspartate residue in the active site (WCGDC). To
      elucidate the physiological roles of the two Trx paralogues, deletion mutants
      DeltatrxA, DeltatrxD and DeltatrxADeltatrxD were constructed. In general, the
      DeltatrxADeltatrxD strain was significantly more sensitive than either of the
      DeltatrxA and DeltatrxD mutants. Upon exposure to oxidative stress, growth of the
      DeltatrxA strain was diminished while that of the DeltatrxD mutant was similar to
      the wild-type. The lack of TrxA also appears to impair methionine sulphoxide
      reduction. Both DeltatrxA and DeltatrxD strains displayed growth inhibition after
      treatment with sodium arsenate and tellurite as compared with the wild-type,
      suggesting partially overlapping functions of TrxA and TrxD. Overall the
      phenotype of the DeltatrxA mutant matches established functions of WCGPC-type Trx
      while TrxD appears to play a more restricted role in stress resistance of Lac.
      lactis. 

PMID- 25564499
TI  - Label-free and redox proteomic analyses of the triacylglycerol-accumulating
      Rhodococcus jostii RHA1.
AB  - The bacterium Rhodococcus jostii RHA1 synthesizes large amounts of
      triacylglycerols (TAGs) under conditions of nitrogen starvation. To better
      understand the molecular mechanisms behind this process, we performed proteomic
      studies in this oleaginous bacterium. Upon nitrogen starvation, we observed a re
      routing of the carbon flux towards the formation of TAGs. Under these conditions,
      the cellular lipid content made up more than half of the cell's dry weight. On
      the proteome level, this coincided with a shift towards non-glycolytic
      carbohydrate-metabolizing pathways. These pathways (Entner-Doudoroff and pentose
      phosphate shunt) contribute NADPH and precursors of glycerol 3-phosphate and
      acetyl-CoA to lipogenesis. The expression of proteins involved in the degradation
      of branched-chain amino acids and the methylmalonyl-CoA pathway probably provided
      propionyl-CoA for the biosynthesis of odd-numbered fatty acids, which make up
      almost 30 % of RHA1 fatty acid composition. Additionally, lipolytic and glycerol
      degrading enzymes increased in abundance, suggesting a dynamic cycling of
      cellular lipids. Conversely, abundance of proteins involved in consuming
      intermediates of lipogenesis decreased. Furthermore, we identified another level
      of lipogenesis regulation through redox-mediated thiol modification in R. jostii.
      Enzymes affected included acetyl-CoA carboxylase and a beta-ketoacyl-[acyl
      carrier protein] synthase II (FabF). An integrative metabolic model for the
      oleaginous RHA1 strain is proposed on the basis of our results. 

PMID- 25564498
TI  - Morphological and biochemical features of Borrelia burgdorferi pleomorphic forms.
AB  - The spirochaete bacterium Borrelia burgdorferi sensu lato is the causative agent
      of Lyme disease, the most common tick-borne infection in the northern hemisphere.
      There is a long-standing debate regarding the role of pleomorphic forms in Lyme
      disease pathogenesis, while very little is known about the characteristics of
      these morphological variants. Here, we present a comprehensive analysis of B.
      burgdorferi pleomorphic formation in different culturing conditions at
      physiological temperature. Interestingly, human serum induced the bacterium to
      change its morphology to round bodies (RBs). In addition, biofilm-like colonies
      in suspension were found to be part of B. burgdorferi's normal in vitro growth.
      Further studies provided evidence that spherical RBs had an intact and flexible
      cell envelope, demonstrating that they are not cell wall deficient, or
      degenerative as previously implied. However, the RBs displayed lower metabolic
      activity compared with spirochaetes. Furthermore, our results indicated that the
      different pleomorphic variants were distinguishable by having unique biochemical
      signatures. Consequently, pleomorphic B. burgdorferi should be taken into
      consideration as being clinically relevant and influence the development of novel
      diagnostics and treatment protocols. 

PMID- 25564501
TI  - Bicultural Straddling Among Immigrant Adolescents: A Concept Analysis.
AB  - BACKGROUND: Increasing population diversity in the United States creates
      challenges for providing culturally responsive health care to immigrant
      adolescents. Nursing providers have few effective concepts to guide their
      understanding of how culturally diverse adolescents handle different cultural
      influences (between family and society) and how straddling two cultures may
      influence adolescents' decision making about health. AIM: Bicultural straddling
      is defined as an ongoing process of adaptation resulting from living within two
      different cultural influences. A concept analysis of bicultural straddling is
      important to nursing professionals in caring for culturally diverse adolescents.
      METHOD: Walker and Avant's methodology was used to guide our understanding about
      how immigrant adolescents straddle cultural influences between their homes and
      society. RESULTS: Straddling two different cultures influences adolescents'
      health-related beliefs, attitudes, perceptions, and behaviors as they navigate
      everyday struggles to make informed health decisions. Adolescents' ability to
      achieve active straddling will allow them to experience positive social
      functioning, psychological development, and health outcomes. CONCLUSIONS: By
      understanding the ongoing process of "bicultural straddling" as a balancing act,
      nurse professionals can develop effective interventions to alleviate stress
      derived from acculturation among immigrant families and ultimately help
      adolescents achieve biculturalism.

PMID- 25564500
TI  - OPA1-related auditory neuropathy: site of lesion and outcome of cochlear
      implantation.
AB  - Hearing impairment is the second most prevalent clinical feature after optic
      atrophy in dominant optic atrophy associated with mutations in the OPA1 gene. In
      this study we characterized the hearing dysfunction in OPA1-linked disorders and
      provided effective rehabilitative options to improve speech perception. We
      studied two groups of OPA1 subjects, one comprising 11 patients (seven males; age
      range 13-79 years) carrying OPA1 mutations inducing haploinsufficiency, the
      other, 10 subjects (three males; age range 5-58 years) carrying OPA1 missense
      mutations. Both groups underwent audiometric assessment with pure tone and speech
      perception evaluation, and otoacoustic emissions and auditory brainstem response
      recording. Cochlear potentials were recorded through transtympanic
      electrocochleography from the group of patients harbouring OPA1 missense
      mutations and were compared to recordings obtained from 20 control subjects with
      normal hearing and from 19 subjects with cochlear hearing loss. Eight patients
      carrying OPA1 missense mutations underwent cochlear implantation. Speech
      perception measures and electrically-evoked auditory nerve and brainstem
      responses were obtained after 1 year of cochlear implant use. Nine of 11 patients
      carrying OPA1 mutations inducing haploinsufficiency had normal hearing function.
      In contrast, all but one subject harbouring OPA1 missense mutations displayed
      impaired speech perception, abnormal brainstem responses and presence of
      otoacoustic emissions consistent with auditory neuropathy. In
      electrocochleography recordings, cochlear microphonic had enhanced amplitudes
      while summating potential showed normal latency and peak amplitude consistent
      with preservation of both outer and inner hair cell activities. After cancelling
      the cochlear microphonic, the synchronized neural response seen in both normally
      hearing controls and subjects with cochlear hearing loss was replaced by a
      prolonged, low-amplitude negative potential that decreased in both amplitude and
      duration during rapid stimulation consistent with neural generation. The use of
      cochlear implant improved speech perception in all but one patient. Brainstem
      potentials were recorded in response to electrical stimulation in five of six
      subjects, whereas no compound action potential was evoked from the auditory nerve
      through the cochlear implant. These findings indicate that underlying the hearing
      impairment in patients carrying OPA1 missense mutations is a disordered synchrony
      in auditory nerve fibre activity resulting from neural degeneration affecting the
      terminal dendrites. Cochlear implantation improves speech perception and
      synchronous activation of auditory pathways by bypassing the site of lesion. 

PMID- 25564502
TI  - Adhesion of mutans streptococci to self-ligating ceramic brackets: in vivo
      quantitative analysis with real-time polymerase chain reaction.
AB  - OBJECTIVE: To analyze in vivo mutans streptococci (MS) adhesion to self-ligating
      ceramic brackets [Clarity-SL (CSL) and Clippy-C (CC)] and the relationships
      between bacterial adhesion and oral hygiene indices. MATERIALS AND METHODS: Four
      central incisor brackets from the maxilla and mandible were collected from 40
      patients (20 patients per each bracket type) at debonding immediately after
      plaque and gingival indices were measured. Adhesions of Streptococcus mutans, S.
      sobrinus, and total bacteria were quantitatively determined using real-time
      polymerase chain reaction after genomic DNA was extracted. Factorial analysis of
      variance was used to analyze bacterial adhesion to the brackets with respect to
      the bracket type and jaw position. Correlation coefficients were calculated to
      determine the relationships of bacterial adhesion to oral hygiene indices.
      RESULTS: Adhesion of total bacteria and S. mutans to CSL was higher than that to
      CC (P < 0.001). Adhesion of total bacteria to the mandibular brackets was higher
      than that to the maxillary ones (P < 0.001), while adhesion of S. mutans to the
      maxillary brackets were higher than that in the mandibular ones (P < 0.001). In
      particular, the proportion of S. mutans to total bacteria in CSL was higher than
      CC (P < 0.05) in the maxillary anterior teeth (P < 0.001). There were no
      significant differences in adhesion of S. sobrinus between the brackets and jaw
      positions. Interestingly, no significant relationships were found between
      bacterial adhesions and oral hygiene indices. LIMITATIONS: Complex bracket
      configurations may significantly influence bacterial adhesion to orthodontic
      brackets. Further in vivo study using bracket raw materials will help to define
      the relationships between bacteria adhesion and enamel demineralization.
      CONCLUSIONS: Because oral hygiene indices were not significantly correlated with
      adhesions of MS to self-ligating ceramic brackets, careful examinations around
      the brackets should be needed to prevent enamel demineralization, regardless of
      oral hygiene status.

PMID- 25564503
TI  - Three dimensional anatomical exploration of the anterior hard palate at the level
      of the third ruga for the placement of mini-implants--a cone-beam CT study.
AB  - AIM: The aim of this retrospective investigation was to measure vertical bone
      thickness on the hard palate, determine areas with adequate bone for the
      insertion of orthodontic mini-implants (MIs), and provide clinical guidelines for
      identification of those areas. MATERIALS AND METHODS: Pre-treatment records of
      1007 patients were reviewed by a single examiner. A total of 125 records
      fulfilled the inclusion criteria and were further investigated. Bone measurements
      were performed on cone-beam computed tomography scans, at a 90 degrees  angle to
      the bone surface, on 28 predetermined and standardized points on the hard palate.
      Bone thickness at various areas was associated to clinically identifiable areas
      on the hard palate by means of pre-treatment plaster models. RESULTS: Bone
      thickness ranged between 1.51 and 13.86 mm (total thickness) and 0.33 and 1.65 mm
      (cortical bone thickness), respectively. Bone thickness was highest in the
      anterior palate and decreased significantly towards more posterior areas. Plaster
      model analysis revealed that bone thickness was highest at the level of the third
      palatal ruga. CONCLUSIONS: The areas on the anterior palate with adequate bone
      thickness for successful insertion of orthodontic MI correspond to the region of
      the third palatal ruga. These results provide stable and clinically identifiable
      landmarks for the insertion of palatal MIs.

PMID- 25564504
TI  - Comparison of short-term effects of mini-implant-supported maxillary expansion
      appliance with two conventional expansion protocols.
AB  - OBJECTIVE: This study evaluates the dentoskeletal effects of a mini-implant
      supported maxillary expansion (MISME) appliance in comparison with two types of
      conventional expansion methods. METHODS: Records of 42 patients with bilateral or
      unilateral posterior crossbite were included in this study. The patients were
      divided into three groups. In group 1, four miniscrews were placed to the palatal
      region and an acrylic expansion device was bonded on these screws. A bonded
      maxillary expansion appliance was used in group 2, while a banded expansion
      appliance was used in group 3. Measurements from cephalometric, postero-anterior
      radiographs, and dental casts taken before and after expansion were evaluated
      statistically. RESULTS: ANB angle increased significantly in group 1 and 3. MISME
      group also showed an increase of SNA angle. Measurements regarding the vertical
      dimension did not change with MISME but significant posterior rotation was found
      in group 2 and 3. Overbite value showed a significant decrease in group 2 and 3,
      but remained stable in group 1. The nasal, maxillary, maxillary intermolar widths
      showed significant increases in all groups. The difference between MISME group
      and other groups in maxillary width was significant indicating more skeletal
      expansion in MISME group. The maxillary molars showed significant buccal tipping
      in group 2 and 3, while lingual tipping of molars was found in MISME group.
      CONCLUSIONS: MISME can be a better alternative to bonded expansion particularly
      in patients with vertical growth patterns and lack of anchorage teeth.

PMID- 25564505
TI  - Changes in joint space dimension after the correction of Class II division 1
      malocclusion.
AB  - OBJECTIVE: The aim of this prospective longitudinal investigation was to compare
      the relationship between the temporomandibular joint (TMJ) condyles and the
      temporal fossae by means of tomography before and after the orthodontic
      correction of Class II, division 1 malocclusion using the activator appliance.
      MATERIALS AND METHODS: The final sample consisted of 26 consecutively treated
      Class II, division 1 patients (19 boys and 7 girls with an average pre-treatment
      age of 11 years) who underwent orthodontic treatment by means of an activator
      appliance. Before treatment all patients were free of signs and symptoms
      associated to TMJ disorders. Bilateral tomographic records before and after
      treatment were taken and analyzed. Outlines of the condyle and temporal fossa
      were automatically determined by an edge-detection protocol, and the minimum
      joint space dimension was automatically measured every 2 degrees. For further
      analysis, the joint space was divided into anterior, superior, and posterior
      joint spaces. RESULTS: The average treatment time with the activator appliance
      was 366 days. In all subjects, activator treatment resulted in a Class I dental
      arch relationship. After activator treatment, no differences were found in the
      joint space measurements in any direction. Comparisons between the right and left
      condyles were not significantly different. CONCLUSIONS: Joint space dimension in
      Class II division I children was similar before and after treatment in both TMJs.

PMID- 25564506
TI  - Robotic left ventricular epicardial lead positioning.
AB  - Cardiac resynchronization therapy is indicated in advanced heart failure patients
      with a wide QRS complex, because it restores the synchronicity of the
      atrioventricular, interventricular and intraventricular contractions. It is
      performed through endovascular implantation of one or more leads. Left cardiac
      lead positioning is one of the most challenging procedures in interventional
      cardiology; unfortunately, in up to 40% of cases no clinical improvements occur.
      Surgical implantation of a left ventricular lead is indicated in cases of failure
      or predicted unfeasibility of a transvenous positioning. Several surgical
      techniques have been described for implantation of left ventricular lead.
      Minimally invasive approaches, including video-assisted thoracic and robotic
      surgery, are favoured due to reduced trauma, pain and recovery time. Robotic
      surgery confers significant advantages for visualization and manoeuverability,
      which are important in patients with a history of cardiac surgery, in whom
      scarring and adhesions may render placement challenging. We describe here the
      surgical technique for robotic implantation of left ventricular leads in
      candidates for cardiac resynchronization therapy. 

PMID- 25564508
TI  - RETRACTED: Do phosphorylcholine-coated and uncoated oxygenators differ in terms
      of elicitation of cellular immune response during cardiopulmonary bypass surgery?

PMID- 25564507
TI  - Cardiopulmonary bypass changes the plasma proteome in children undergoing
      tetralogy of Fallot repair.
AB  - INTRODUCTION: Cardiopulmonary bypass (CPB) can be associated with deleterious
      clinical effects. However, the impact of CPB on inflammatory, immunological and
      other homeostatic pathways remains poorly understood. We investigated the impact
      of CPB on the plasma proteome in children undergoing tetralogy of Fallot repair.
      METHODS: Blood samples were taken from 20 children prior to and at the end of CPB
      and 6h, 12h and 24h after CPB. Plasma was analysed by liquid chromatography-mass
      spectrometry (LC-MS) in a label-free, untargeted approach. Data were analysed
      using Genedata software to identify peptides that were differentially expressed
      (p<0.01 above a false discovery rate). Proteins were identified from peptides
      that demonstrated differential expression. RESULTS: The proteins that were found
      to be differentially expressed were haptoglobin isoform 1 preproprotein, isoform
      2 of semaphorin-6C, vitamin D-binding protein, inter-alpha-trypsin inhibitor,
      ceruloplasmin, apolipoprotein B100 and fibrinogen alpha. CONCLUSION: CPB alters
      the plasma proteome with differences most apparent at 6h and 12h post CPB. There
      was a return to baseline with no proteins differentially regulated by 24h.

PMID- 25564509
TI  - Usefulness of elevated red cell distribution width for predicting systemic
      inflammatory response syndrome after extracorporeal circulation.
AB  - OBJECTIVES: Cardiac surgical operations performed by using extracorporeal
      circulation (ECC) lead to a systemic inflammatory response (SIR). Sometimes SIR
      may turn into a severe state, the systemic inflammatory response syndrome (SIRS)
      that usually has a poor outcome with no specific clinical tools described for its
      prediction. Red cell distribution width (RDW) is a routine hematological
      parameter. It has been proposed as a marker of morbidity and mortality in various
      clinical conditions. We aimed to investigate the relationship between high RDW
      and SIRS which is triggered by ECC. METHODS: Eleven hundred consecutive patients
      who underwent elective heart surgery with the use of ECC were retrospectively
      analyzed. A total of 19 patients fulfilled the described SIRS criteria and 20
      consecutive patients were selected as the control group. RDW and other laboratory
      parameters, preoperative clinical status, operative data and postoperative data
      were compared between the SIRS and the control groups. RESULTS: Baseline
      characteristics of the patient groups were similar. Significant mortality was
      found in the SIRS group; 18 (94.73%) patients and 2 (10%) patients in the control
      group (p < 0.002). RDW was found to be significantly higher in the SIRS group vs
      the control group (15.02 +/- 2.03 vs 13.01 +/- 1.93, respectively, p < 0.003).
      Multiple logistic regression analyses showed an association between high RDW
      levels and SIRS development (OR for RDW levels exceeding 13.5%; 95% confidence
      limits of 1.0-1.3; p < 0.04). Total operation time and the need for inotropic
      support were also found to be significant against the SIRS group (p = 0.049).
      CONCLUSION: Increased RDW was significantly associated with increased risk of
      SIRS after ECC. The results of this study suggest that paying attention to RDW
      might provide valuable clinical information for predicting SIRS development among
      patients who are candidates for open heart surgery, without incurring additional
      costs.

PMID- 25564510
TI  - Modular minimally invasive extracorporeal circulation systems; can they become
      the standard practice for performing cardiac surgery?
AB  - Minimally invasive extracorporeal circulation (MiECC) has been developed in an
      attempt to integrate all advances in cardiopulmonary bypass technology in one
      closed circuit that shows improved biocompatibility and minimizes the systemic
      detrimental effects of CPB. Despite well-evidenced clinical advantages,
      penetration of MiECC technology into clinical practice is hampered by concerns
      raised by perfusionists and surgeons regarding air handling together with blood
      and volume management during CPB. We designed a modular MiECC circuit, bearing an
      accessory circuit for immediate transition to an open system that can be used in
      every adult cardiac surgical procedure, offering enhanced safety features. We
      challenged this modular circuit in a series of 50 consecutive patients. Our
      results showed that the modular AHEPA circuit design offers 100% technical
      success rate in a cohort of random, high-risk patients who underwent complex
      procedures, including reoperation and valve and aortic surgery, together with
      emergency cases. This pilot study applies to the real world and prompts for
      further evaluation of modular MiECC systems through multicentre trials. 

PMID- 25564514
TI  - Host specificity in vascular epiphytes: a review of methodology, empirical
      evidence and potential mechanisms.
AB  - Information on the degree of host specificity is fundamental for an understanding
      of the ecology of structurally dependent plants such as vascular epiphytes.
      Starting with the seminal paper of A.F.W. Schimper on epiphyte ecology in the
      late 19th century over 200 publications have dealt with the issue of host
      specificity in vascular epiphytes. We review and critically discuss this
      extensive literature. The available evidence indicates that host ranges of
      vascular epiphytes are largely unrestricted while a certain host bias is
      ubiquitous. However, tree size and age and spatial autocorrelation of tree and
      epiphyte species have not been adequately considered in most statistical
      analyses. More refined null expectations and adequate replication are needed to
      allow more rigorous conclusions. Host specificity could be caused by a large
      number of tree traits (e.g. bark characteristics and architectural traits), which
      influence epiphyte performance. After reviewing the empirical evidence for their
      relevance, we conclude that future research should use a more comprehensive
      approach by determining the relative importance of various potential mechanisms
      acting locally and by testing several proposed hypotheses regarding the relative
      strength of host specificity in different habitats and among different groups of
      structurally dependent flora. 

PMID- 25564515
TI  - Collaboration between grass seedlings and rhizobacteria to scavenge organic
      nitrogen in soils.
AB  - Plants require nitrogen (N) to make proteins, nucleic acids and other biological
      molecules. It is widely accepted that plants absorb inorganic forms of N to fill
      their needs. However, recently it has become clear that plants also have the
      capacity to absorb organic N from soils. In this paper we describe a new kind of
      symbiosis involving seed-vectored rhizobacteria and grasses that is targeted at
      enhancing acquisition of organic N from soils. Our proposal is based on results
      of experiments on seedlings of grass species Festuca arundinacea Schreb., Lolium
      perenne L. and Poa annua L. that suggest: (i) seed-vectored rhizobacteria
      colonize seedling roots and influence their development; (ii) reactive oxygen
      secretion by seedling roots plays a role in organic N procurement by denaturing
      microbial proteins in the vicinity of roots (daytime activity); and (iii) plant
      root and microbial proteases degrade denatured proteins prior to absorption by
      roots (night-time activity). This research involved the following types of
      studies: (i) seedling root development experiments with and without rhizobacteria
      on a variety of substrates in agarose media and (ii) isotopic N-tracking
      experiments to evaluate the absorption into seedlings of N obtained from
      degradation of proteins. We hypothesize that grasses, in particular, are adapted
      to scavenge organic N from soils through application of this 'oxidative nitrogen
      scavenging' symbiosis with rhizobacteria, and their soil-permeating root systems.
      This newly discovered symbiosis in grass species could lead to new ways to
      cultivate and manage grasses to enhance efficiency of N utilization and reduce
      applications of inorganic fertilizers. 

PMID- 25564518
TI  - On peer review--the cornerstone of scientific publication.

PMID- 25564516
TI  - Lysine demethylase KDM4A associates with translation machinery and regulates
      protein synthesis.
AB  - Chromatin-modifying enzymes are predominantly nuclear; however, these factors are
      also localized to the cytoplasm, and very little is known about their role in
      this compartment. In this report, we reveal a non-chromatin-linked role for the
      lysine-specific demethylase KDM4A. We demonstrate that KDM4A interacts with the
      translation initiation complex and affects the distribution of translation
      initiation factors within polysome fractions. Furthermore, KDM4A depletion
      reduced protein synthesis and enhanced the protein synthesis suppression observed
      with mTOR inhibitors, which paralleled an increased sensitivity to these drugs.
      Finally, we demonstrate that JIB-04, a JmjC demethylase inhibitor, suppresses
      translation initiation and enhances mTOR inhibitor sensitivity. These data
      highlight an unexpected cytoplasmic role for KDM4A in regulating protein
      synthesis and suggest novel potential therapeutic applications for this class of
      enzyme. SIGNIFICANCE: This report documents an unexpected cytoplasmic role for
      the lysine demethylase KDM4A. We demonstrate that KDM4A interacts with the
      translation initiation machinery, regulates protein synthesis and, upon
      coinhibition with mTOR inhibitors, enhances the translation suppression and cell
      sensitivity to these therapeutics.

PMID- 25564517
TI  - A coding single-nucleotide polymorphism in lysine demethylase KDM4A associates
      with increased sensitivity to mTOR inhibitors.
AB  - SNPs occur within chromatin-modulating factors; however, little is known about
      how these variants within the coding sequence affect cancer progression or
      treatment. Therefore, there is a need to establish their biochemical and/or
      molecular contribution, their use in subclassifying patients, and their impact on
      therapeutic response. In this report, we demonstrate that coding SNP-A482 within
      the lysine tridemethylase gene KDM4A/JMJD2A has different allelic frequencies
      across ethnic populations, associates with differential outcome in patients with
      non-small cell lung cancer (NSCLC), and promotes KDM4A protein turnover. Using an
      unbiased drug screen against 87 preclinical and clinical compounds, we
      demonstrate that homozygous SNP-A482 cells have increased mTOR inhibitor
      sensitivity. mTOR inhibitors significantly reduce SNP-A482 protein levels, which
      parallels the increased drug sensitivity observed with KDM4A depletion. Our data
      emphasize the importance of using variant status as candidate biomarkers and
      highlight the importance of studying SNPs in chromatin modifiers to achieve
      better targeted therapy. SIGNIFICANCE: This report documents the first coding SNP
      within a lysine demethylase that associates with worse outcome in patients with
      NSCLC. We demonstrate that this coding SNP alters the protein turnover and
      associates with increased mTOR inhibitor sensitivity, which identifies a
      candidate biomarker for mTOR inhibitor therapy and a therapeutic target for
      combination therapy.

PMID- 25564519
TI  - Parallel functional changes in independent testis-specific duplicates of Aldehyde
      dehydrogenase in Drosophila.
AB  - A large proportion of duplicates, originating from ubiquitously expressed genes,
      acquire testis-biased expression. Identifying the underlying cause of this
      observation requires determining whether the duplicates have altered functions
      relative to the parental genes. Typically, statistical methods are used to test
      for positive selection, signature of which in protein sequence of duplicates
      implies functional divergence. When assumptions are violated, however, such tests
      can lead to false inference of positive selection. More convincing evidence for
      naturally selected functional changes would be the occurrence of structural
      changes with similar functional consequences in independent duplicates of the
      same gene. We investigated two testis-specific duplicates of the broadly
      expressed enzyme gene Aldehyde dehydrogenase (Aldh) that arose in different
      Drosophila lineages. The duplicates show a typical pattern of accelerated amino
      acid substitutions relative to their broadly expressed paralogs, with statistical
      evidence for positive selection in both cases. Importantly, in both duplicates,
      width of the entrance to the substrate binding site, known a priori to influence
      substrate specificity, and otherwise conserved throughout the genus Drosophila,
      has been reduced, resulting in narrowing of the entrance. Protein structure
      modeling suggests that the reduction of the size of the enzyme's substrate entry
      channel, which is likely to shift substrate specificity toward smaller aldehydes,
      is accounted for by the positively selected parallel substitutions in one
      duplicate but not the other. Evolution of the testis-specific duplicates was
      accompanied by reduction in expression of the ancestral Aldh in males, supporting
      the hypothesis that the duplicates may have helped resolve intralocus sexual
      conflict over Aldh function. 

PMID- 25564520
TI  - Genetic and pharmacological inactivation of the purinergic P2RX7 receptor dampens
      inflammation but increases tumor incidence in a mouse model of colitis-associated
      cancer.
AB  - Colitis-associated cancer (CAC) is a complication of inflammatory bowel disease
      (IBD). Binding of extracellular ATP to the purinergic receptor P2RX7 has emerged
      as a critical event in controlling intestinal inflammation, acting to limit
      elevation of proinflammatory mast cells and cytokines and promote survival of
      regulatory T cells (Treg) and enteric neurons. In this study, we investigated the
      effect of P2RX7 blockade in an established mouse model of CAC. Using genetic and
      pharmacologic tools, we found unexpectedly that while P2RX7 mediated inflammatory
      responses, it also acted at an early time to suppress CAC development. P2RX7
      blockade enhanced proliferation of intestinal epithelial cells and protected them
      from apoptosis. The proliferative effects of P2RX7 blockade were associated with
      an increased production of TGFbeta1 that was sufficient to stimulate the
      proliferation of intestinal epithelial cells. Finally, P2RX7 blockade also
      altered immune cell infiltration and promoted Treg accumulation within lesions of
      the digestive system. Taken together, our findings reveal an unexpected role for
      P2RX7 in preventing CAC, suggesting cautions in the use of P2RX7 inhibitors to
      treat IBD given the possibility of increasing risks CAC as a result.

PMID- 25564522
TI  - In search of an association between conception risk and prejudice.

PMID- 25564521
TI  - Expression of anger and ill health in two cultures: an examination of
      inflammation and cardiovascular risk.
AB  - Expression of anger is associated with biological health risk (BHR) in Western
      cultures. However, recent evidence documenting culturally divergent functions of
      the expression of anger suggests that its link with BHR may be moderated by
      culture. To test this prediction, we examined large probability samples of both
      Japanese and Americans using multiple measures of BHR, including pro-inflammatory
      markers (interleukin-6 and C-reactive protein) and indices of cardiovascular
      malfunction (systolic blood pressure and ratio of total to HDL cholesterol). We
      found that the link between greater expression of anger and increased BHR was
      robust for Americans. As predicted, however, this association was diametrically
      reversed for Japanese, among whom greater expression of anger predicted reduced
      BHR. These patterns were unique to the expressive facet of anger and remained
      after we controlled for age, gender, health status, health behaviors, social
      status, and reported experience of negative emotions. Implications for
      sociocultural modulation of bio-physiological responses are discussed.

PMID- 25564523
TI  - Amnesia for object attributes: failure to report attended information that had
      just reached conscious awareness.
AB  - People intuitively believe that when they become consciously aware of a visual
      stimulus, they will be able to remember it and immediately report it. The present
      study provides a series of striking demonstrations of behavior that is
      inconsistent with such an intuition. Four experiments showed that in certain
      conditions, participants could not report an attribute (e.g., letter identity) of
      a stimulus even when that attribute had been attended and had reached a full
      state of conscious awareness just prior to being questioned about it. We term
      this effect attribute amnesia, and it occurs when participants repeatedly locate
      a target using one attribute and are then unexpectedly asked to report that
      attribute. This discovery suggests that attention to and awareness of a stimulus
      attribute are insufficient to ensure its immediate reportability. These results
      imply that when attention is configured by using an attribute for target
      selection, that attribute will not necessarily be remembered. 

PMID- 25564524
TI  - Targeted rejection predicts decreased anti-inflammatory gene expression and
      increased symptom severity in youth with asthma.
AB  - Although responses to different stressors are sometimes assumed to be similar,
      recent research has demonstrated that certain types of stress, such as targeted
      rejection, are particularly potent. To test such associations in a chronic
      disease model, we examined how noninterpersonal, interpersonal, and targeted
      rejection major life events predicted changes in gene expression and symptom
      severity in 121 youths with asthma who were assessed every 6 months for 2 years.
      Youths who had recently experienced targeted rejection had lower messenger RNA
      expression for signaling molecules that control airway inflammation and
      obstruction (specifically, the glucocorticoid receptor and beta2-adrenergic
      receptor) than youths who had not experienced targeted rejection. These
      associations were specific to targeted rejection and stronger for youths higher
      in subjective social status. Higher-status youths exposed to targeted rejection
      (but not other types of stress) also reported more asthma symptoms. These data
      demonstrate stressor-specific associations with molecular-signaling pathways and
      the severity of asthma, and they suggest that threats to the social self may be
      particularly deleterious.

PMID- 25564525
TI  - Escherichia coli antitoxin MazE as transcription factor: insights into MazE-DNA
      binding.
AB  - Toxin-antitoxin (TA) modules are pairs of genes essential for bacterial
      regulation upon environmental stresses. The mazEF module encodes the MazF toxin
      and its cognate MazE antitoxin. The highly dynamic MazE possesses an N-terminal
      DNA binding domain through which it can negatively regulate its own promoter.
      Despite being one of the first TA systems studied, transcriptional regulation of
      Escherichia coli mazEF remains poorly understood. This paper presents the
      solution structure of C-terminal truncated E. coli MazE and a MazE-DNA model with
      a DNA palindrome sequence ~ 10 bp upstream of the mazEF promoter. The work has
      led to a transcription regulator-DNA model, which has remained elusive thus far
      in the E. coli toxin-antitoxin family. Multiple complementary techniques
      including NMR, SAXS and ITC show that the long intrinsically disordered C-termini
      in MazE, required for MazF neutralization, does not affect the interactions
      between the antitoxin and its operator. Rather, the MazE C-terminus plays an
      important role in the MazF binding, which was found to increase the MazE affinity
      for the palindromic single site operator.

PMID- 25564526
TI  - Recognition and cleavage of 5-methylcytosine DNA by bacterial SRA-HNH proteins.
AB  - SET and RING-finger-associated (SRA) domain is involved in establishment and
      maintenance of DNA methylation in eukaryotes. Proteins containing SRA domains
      exist in mammals, plants, even microorganisms. It has been established that
      mammalian SRA domain recognizes 5-methylcytosine (5mC) through a base-flipping
      mechanism. Here, we identified and characterized two SRA domain-containing
      proteins with the common domain architecture of N-terminal SRA domain and C
      terminal HNH nuclease domain, Sco5333 from Streptomyces coelicolor and Tbis1 from
      Thermobispora bispora. Both sco5333 and tbis1 cannot establish in methylated
      Escherichia coli hosts (dcm(+)), and this in vivo toxicity requires both SRA and
      HNH domain. Purified Sco5333 and Tbis1 displayed weak DNA cleavage activity in
      the presence of Mg(2+), Mn(2+) and Co(2+) and the cleavage activity was
      suppressed by Zn(2+). Both Sco5333 and Tbis1 bind to 5mC-containing DNA in all
      sequence contexts and have at least a preference of 100 folds in binding affinity
      for methylated DNA over non-methylated one. We suggest that linkage of methyl
      specific SRA domain and weakly active HNH domain may represent a universal
      mechanism in competing alien methylated DNA but to maximum extent minimizing
      damage to its own chromosome. 

PMID- 25564527
TI  - iRNA-seq: computational method for genome-wide assessment of acute
      transcriptional regulation from total RNA-seq data.
AB  - RNA-seq is a sensitive and accurate technique to compare steady-state levels of
      RNA between different cellular states. However, as it does not provide an account
      of transcriptional activity per se, other technologies are needed to more
      precisely determine acute transcriptional responses. Here, we have developed an
      easy, sensitive and accurate novel computational method, IRNA-SEQ: , for genome
      wide assessment of transcriptional activity based on analysis of intron coverage
      from total RNA-seq data. Comparison of the results derived from iRNA-seq analyses
      with parallel results derived using current methods for genome-wide determination
      of transcriptional activity, i.e. global run-on (GRO)-seq and RNA polymerase II
      (RNAPII) ChIP-seq, demonstrate that iRNA-seq provides similar results in terms of
      number of regulated genes and their fold change. However, unlike the current
      methods that are all very labor-intensive and demanding in terms of sample
      material and technologies, iRNA-seq is cheap and easy and requires very little
      sample material. In conclusion, iRNA-seq offers an attractive novel alternative
      to current methods for determination of changes in transcriptional activity at a
      genome-wide level.

PMID- 25564528
TI  - RNA helicase A activity is inhibited by oncogenic transcription factor EWS-FLI1.
AB  - RNA helicases impact RNA structure and metabolism from transcription through
      translation, in part through protein interactions with transcription factors.
      However, there is limited knowledge on the role of transcription factor influence
      upon helicase activity. RNA helicase A (RHA) is a DExH-box RNA helicase that
      plays multiple roles in cellular biology, some functions requiring its activity
      as a helicase while others as a protein scaffold. The oncogenic transcription
      factor EWS-FLI1 requires RHA to enable Ewing sarcoma (ES) oncogenesis and growth;
      a small molecule, YK-4-279 disrupts this complex in cells. Our current study
      investigates the effect of EWS-FLI1 upon RHA helicase activity. We found that EWS
      FLI1 reduces RHA helicase activity in a dose-dependent manner without affecting
      intrinsic ATPase activity; however, the RHA kinetics indicated a complex model.
      Using separated enantiomers, only (S)-YK-4-279 reverses the EWS-FLI1 inhibition
      of RHA helicase activity. We report a novel RNA binding property of EWS-FLI1
      leading us to discover that YK-4-279 inhibition of RHA binding to EWS-FLI1
      altered the RNA binding profile of both proteins. We conclude that EWS-FLI1
      modulates RHA helicase activity causing changes in overall transcriptome
      processing. These findings could lead to both enhanced understanding of
      oncogenesis and provide targets for therapy. 

PMID- 25564529
TI  - Recognition of duplex RNA by the deaminase domain of the RNA editing enzyme
      ADAR2.
AB  - Adenosine deaminases acting on RNA (ADARs) hydrolytically deaminate adenosines
      (A) in a wide variety of duplex RNAs and misregulation of editing is correlated
      with human disease. However, our understanding of reaction selectivity is
      limited. ADARs are modular enzymes with multiple double-stranded RNA binding
      domains (dsRBDs) and a catalytic domain. While dsRBD binding is understood,
      little is known about ADAR catalytic domain/RNA interactions. Here we use a
      recently discovered RNA substrate that is rapidly deaminated by the isolated
      human ADAR2 deaminase domain (hADAR2-D) to probe these interactions. We
      introduced the nucleoside analog 8-azanebularine (8-azaN) into this RNA (and
      derived constructs) to mechanistically trap the protein-RNA complex without
      catalytic turnover for EMSA and ribonuclease footprinting analyses. EMSA showed
      that hADAR2-D requires duplex RNA and is sensitive to 2'-deoxy substitution at
      nucleotides opposite the editing site, the local sequence and 8-azaN nucleotide
      positioning on the duplex. Ribonuclease V1 footprinting shows that hADAR2-D
      protects ~ 23 nt on the edited strand around the editing site in an asymmetric
      fashion (~ 18 nt on the 5' side and ~ 5 nt on the 3' side). These studies provide
      a deeper understanding of the ADAR catalytic domain-RNA interaction and new tools
      for biophysical analysis of ADAR-RNA complexes.

PMID- 25564530
TI  - Global coordination in adaptation to gene rewiring.
AB  - Gene rewiring is a common evolutionary phenomenon in nature that may lead to
      extinction for living organisms. Recent studies on synthetic biology demonstrate
      that cells can survive genetic rewiring. This survival (adaptation) is often
      linked to the stochastic expression of rewired genes with random transcriptional
      changes. However, the probability of adaptation and the underlying common
      principles are not clear. We performed a systematic survey of an assortment of
      gene-rewired Escherichia coli strains to address these questions. Three different
      cell fates, designated good survivors, poor survivors and failures, were observed
      when the strains starved. Large fluctuations in the expression of the rewired
      gene were commonly observed with increasing cell size, but these changes were
      insufficient for adaptation. Cooperative reorganizations in the corresponding
      operon and genome-wide gene expression largely contributed to the final success.
      Transcriptome reorganizations that generally showed high-dimensional dynamic
      changes were restricted within a one-dimensional trajectory for adaptation to
      gene rewiring, indicating a general path directed toward cellular plasticity for
      a successful cell fate. This finding of global coordination supports a mechanism
      of stochastic adaptation and provides novel insights into the design and
      application of complex genetic or metabolic networks. 

PMID- 25564532
TI  - The larynx and caustic soda ingestion.

PMID- 25564531
TI  - Structural insight into operator dre-sites recognition and effector binding in
      the GntR/HutC transcription regulator NagR.
AB  - The uptake and metabolism of N-acetylglucosamine (GlcNAc) in Bacillus subtilis is
      controlled by NagR (formerly named YvoA), a member of the widely-occurring
      GntR/HutC family of transcription regulators. Upon binding to specific DNA
      operator sites (dre-sites) NagR blocks the transcription of genes for GlcNAc
      utilization and interaction of NagR with effectors abrogates gene repression.
      Here we report crystal structures of NagR in complex with operator DNA and in
      complex with the putative effector molecules glucosamine-6-phosphate (GlcN-6-P)
      and N-acetylglucosamine-6-phosphate (GlcNAc-6-P). A comparison of the distinct
      conformational states suggests that effectors are able to displace the NagR-DNA
      binding domains (NagR-DBDs) by almost 70 A upon binding. In addition, a high
      resolution crystal structure of isolated NagR-DBDs in complex with palindromic
      double-stranded DNA (dsDNA) discloses both the determinants for highly sequence
      specific operator dre-site recognition and for the unspecific binding of NagR to
      dsDNA. Extensive biochemical binding studies investigating the affinities of full
      length NagR and isolated NagR-DBDs for either random DNA, dre-site-derived
      palindromic or naturally occurring non-palindromic dre-site sequences suggest
      that proper NagR function relies on an effector-induced fine-tuning of the DNA
      binding affinities of NagR and not on a complete abrogation of its DNA binding. 

PMID- 25564535
TI  - Infantile Wernicke's encephalopathy.

PMID- 25564533
TI  - Severe combined immunodeficiency: recent developments and guidance on clinical
      management.
AB  - Severe combined immunodeficiency (SCID) is a rare but important condition.
      Affected infants are born with profound abnormalities of immune cell function
      that lead to severe and recurrent infection that are almost always fatal in the
      first year of life without treatment. Infants with SCID are often initially seen
      by general paediatricians in the hospital care setting, and the recognition of
      the cardinal features of the disease and alertness to specific laboratory
      parameters are important in making an early diagnosis. There is also increasing
      interest in newborn screening for SCID, which has the potential to significantly
      improve outcome through early diagnosis and implementation of prophylactic
      medications. Definitive treatments such as haematopoietic stem cell
      transplantation and gene therapy have also made major advances over the last
      decade and again promise to improve the overall outcome for SCID with reduced
      long-term toxicities. In this review, we highlight some of the major advances in
      diagnosis and management of the disease, but we also want to emphasise the
      important role of the general paediatrician in making an early diagnosis and in
      ongoing management. 

PMID- 25564534
TI  - Acute and late coronary outcomes in 1073 patients with Kawasaki disease with and
      without intravenous gamma-immunoglobulin therapy.
AB  - OBJECTIVE: To explore acute and late coronary outcomes and their risk/modifiers
      in patients with Kawasaki disease (KD). DESIGN: Retrospective study. SETTING AND
      PATIENTS: 1073 patients with KD identified from a tertiary care medical centre
      (1980-2012; 8677 patient-years). MAIN OUTCOME MEASURES: The acute coronary
      severities and late outcomes (survival free of coronary aneurysm persistence and
      ischaemia) were assessed. RESULTS: Coronary arterial lesions occurred in 40.6% of
      cases at their acute febrile stages, and persisted beyond 1 month in 196 (18.3%,
      M/F=138/58) patients: 125 (11.6%) had small aneurysms, 44 (4.1%) had medium
      aneurysms, and 27 (2.5%) had giant aneurysms. At follow-up (1-46 years), coronary
      aneurysms persisted in all with giant aneurysms, in 55% of those with medium
      aneurysms (18% with stenosis), and in 9% of those with small aneurysms. Ischaemia
      events occurred in 14 patients (M/F=13/1) and caused four deaths. Among the
      patients with KD with coronary aneurysms, 10-year ischaemia event-free and
      aneurysm persistence probability was 87.5% and 20.6%, respectively. The only
      independent risk for aneurysm persistence was the aneurysm severity 1 month after
      KD onset (chi(2)=80.73, p<10(-3)). Male patients and intravenous gamma
      immunoglobulin (IVIG) therapy were independent risk factors of initial coronary
      severity but were not associated with the late coronary outcomes, even in
      severity stratified subgroups. CONCLUSIONS: The coronary severity 1 month after
      KD onset is most crucial to the late coronary outcomes. Although IVIG use
      improves the initial severity of coronary lesions, it does not further modify the
      long-term fate of coronary aneurysms.

PMID- 25564536
TI  - Outcome of children with hereditary tyrosinaemia following newborn screening.
AB  - BACKGROUND: Nitisinone has transformed the management of hereditary tyrosinaemia
      type 1 (HT1). However, the risk of developing hepatocellular carcinoma is related
      to the age at which treatment is commenced. Little data on the outcome of
      children treated pre-emptively exist. AIM: To describe the outcome of children
      with HT1 treated with nitisinone following selective newborn screening (NBS) and
      to compare their outcome with index siblings who had presented clinically.
      SUBJECTS: 12 children with HT1 were detected by NBS. Seven children were screened
      for HT1 because of an affected sibling (n=5). Four children were detected due to
      raised tyrosine concentrations on routine NBS and one child was born in a country
      with universal NBS for HT1. OUTCOME: Nitisinone was commenced at 4 (1-52) days
      old. 6 children had an initial coagulopathy which resolved after 4 (1-7) days
      treatment. Currently at median age 8.5 (3-12.5) years all are clinically normal,
      with normal liver function tests and imaging. Those of school age are in normal
      classes but four have reported learning difficulties. Five index siblings
      presented clinically with acute liver failure (four) and chronic liver disease
      (one) at median 4 (1.5-17) months. One died of liver failure prior to
      nitisinone's availability. Four were treated with nitisinone; one failed to
      respond and underwent liver transplantation and three responded. One responder
      died from complications of prematurity and the remaining two have compensated
      liver disease. SUMMARY: Children with HT1 treated with nitisinone following NBS
      have an excellent outcome. CONCLUSIONS: Universal NBS for HT1 should be
      introduced in the UK.

PMID- 25564537
TI  - The impact of social disadvantage in moderate-to-severe chronic kidney disease:
      an equity-focused systematic review.
AB  - It is unclear whether a social gradient in health outcomes exists for people with
      moderate-to-severe chronic kidney disease (CKD). We critically review the
      literature for evidence of social gradients in health and investigate the
      'suitability' of statistical analyses in the primary studies. In this equity
      focused systematic review among adults with moderate-to-severe CKD, factors of
      disadvantage included gender, race/ethnicity, religion, education, socio-economic
      status or social capital, occupation and place of residence. Outcomes included
      access to healthcare, kidney disease progression, cardiovascular events, all
      cause mortality and suitability of analyses. Twenty-four studies in the pre
      dialysis population and 34 in the dialysis population representing 8.9 million
      people from 10 countries were included. In methodologically suitable studies
      among pre-dialysis patients, a significant social gradient was observed in access
      to healthcare for those with no health insurance and no home ownership. Low
      income and no home ownership were associated with higher cardiovascular event
      rates and higher mortality [HR 1.94, 95% confidence interval (CI) 1.27-2.98; HR
      1.28, 95% CI 1.04-1.58], respectively. In methodologically suitable studies among
      dialysis patients, females, ethnic minorities, those with low education, no
      health insurance, low occupational level or no home ownership were significantly
      less likely to access cardiovascular healthcare than their more advantaged
      dialysis counterparts. Low education level and geographic remoteness were
      associated with higher cardiovascular event rates and higher mortality (HR 1.54,
      95% CI 1.01-2.35; HR 1.21, 95% CI 1.08-1.37), respectively. Socially
      disadvantaged pre-dialysis and dialysis patients experience poorer access to
      specialist cardiovascular health services, and higher rates of cardiovascular
      events and mortality than their more advantaged counterparts. 

PMID- 25564539
TI  - Periprocedural complications associated with endovascular treatment of
      intracranial aneurysms in 1764 cases.
AB  - BACKGROUND: Intracranial aneurysms are increasingly treated with endovascular
      treatment. Based on our observation that cerebral complications are associated
      with this treatment, we predict that the number of intraprocedural complications
      will rise as a result of this trend. METHODS: Between January 2007 and December
      2013, 1739 patients underwent 1764 detachable coil embolizations to treat
      intracranial aneurysms (637 ruptured and 1127 unruptured). We reviewed their
      records and images to evaluate the periprocedural complications and related
      morbidity and mortality. RESULTS: 61 complications occurred during coil
      embolization and 33 periprocedural complications occurred within 1 week. These
      complications were observed in 8.6% of ruptured aneurysm embolization procedures
      (55/637) and in 3.5% of unruptured aneurysm embolization procedures (39/1127).
      There were 17 (0.96%) cerebral thromboembolisms, 34 (1.93%) intraprocedural
      aneurysm ruptures, 8 (0.45%) coil migrations, 13 (0.74%) postprocedural
      aneurysmal ruptures, and 22 (1.24%) neurologic deficits or transient neurologic
      deficits related to embolization. 63 complications had no neurologic
      consequences, 3 were associated with transient neurologic morbidity, 15 resulted
      in persistent neurologic morbidity on discharge, and 12 resulted in death. The
      procedure-related neurologic morbidity and mortality rates for all 1764
      procedures were 0.85% in ruptured aneurysms and 0.68% in unruptured aneurysms.
      CONCLUSIONS: The periprocedural complication rate was higher in ruptured
      aneurysms than in unruptured aneurysms. The main causes of morbidity and
      mortality were thromboembolisms, intraprocedural aneurysm perforations, and
      postprocedural aneurysmal ruptures. While some periprocedural complications are
      inevitable, we can minimize the occurrence of such complications by advancing our
      skill and experience, thereby improving patient prognosis.

PMID- 25564540
TI  - Author response: what to do about racial disparities in access to glasses among
      children in the US?

PMID- 25564544
TI  - Time pressure, working time control and long-term sickness absence.
AB  - OBJECTIVES: Perceived time pressure at work has increased in most European
      countries during recent decades. Time pressure may be harmful for employees'
      health and well-being. The aim of this register-based follow-up study is to
      investigate whether the effects of time pressure on long sickness absence vary by
      the level of working time control. METHODS: The data are taken from the Finnish
      Quality of Work Life Survey 2003 (n=3400), a representative sample of Finnish
      employees, combined with a register-based follow-up from Statistics Finland
      covering the years 2002-2006. In the 2003 survey, employees were asked about
      their perceived time pressure and to what extent they had control over working
      time. The register data included information on long-term (more than 10 days)
      sickness absence. A negative binomial model was used in the analysis of long-term
      sickness absence days during 2004-2006. The results are adjusted for several
      background and work-related factors and controlled for baseline absenteeism in
      2002. RESULTS: High working time control decreased and high time pressure
      increased long-term sickness absence. The highest incidence of long-term sickness
      absence was found in time strain situations (high time pressure, low time
      control). However, there was no statistical interaction between working time
      control and time pressure. CONCLUSIONS: Establishments that use working time
      control as a human resource instrument may benefit from reduced absenteeism.
      However, following the 'strain' hypothesis it is insufficient to focus solely on
      working time control as high time pressure maintains its detrimental effect on
      employees' health.

PMID- 25564545
TI  - X chromosome inactivation and active X upregulation in therian mammals: facts,
      questions, and hypotheses.
AB  - X chromosome inactivation is a mechanism that modulates the expression of X
      linked genes in eutherian females (XX). Ohno proposed that to achieve a proper
      balance between X-linked and autosomal genes, those on the active X should also
      undergo a 2-fold upregulation. Although some support for Ohno's hypothesis has
      been provided through the years, recent genomic studies testing this hypothesis
      have brought contradictory results and fueled debate. Thus far, there are as many
      results in favor as against Ohno's hypothesis, depending on the nature of the
      datasets and the various assumptions and thresholds involved in the analyses.
      However, they have confirmed the importance of dosage balance between X-linked
      and autosomal genes involved in stoichiometric relationships. These facts as well
      as questions and hypotheses are discussed below. 

PMID- 25564546
TI  - Optimal conditions for cardiac catheter ablation using photodynamic therapy.
AB  - AIMS: Photodynamic therapy (PDT) is based on non-thermal injury mediated by
      singlet oxygen species and is used clinically in cancer therapy. In our
      continuing efforts to apply this technology to cardiac catheter ablation, we
      clarified the optimal condition for creating PDT-mediated lesions using a laser
      catheter. METHODS AND RESULTS: In a total of 35 canines, we applied a laser
      directly to the epicardium of the beating heart during open-chest surgery at 15
      min after administration of a photosensitizer, talaporfin sodium. We evaluated
      the lesion size (depth and width) using hematoxylin-eosin staining under varying
      conditions as follows: laser output (5, 10, 20 W/cm(2)), irradiation time (0-60
      s), photosensitizer concentration (0, 2.5, 5 mg/kg), blood oxygen concentration
      (103.5 +/- 2.1 vs. 548.0 +/- 18.4 torr), and contact force applied during
      irradiations (low: <20 g, high: >20 g). A laser irradiation at 20 W/cm(2) for 60
      s under 5 mg/kg (29 ug/mL) of photosensitizer induced a lesion 8.7 +/- 0.8 mm
      deep and 5.2 +/- 0.2 mm wide. The lesion size was thus positively correlated to
      the laser power, irradiation time, and photosensitizer concentration, and was
      independent of the applied contact force and oxygen concentration. In addition,
      the concentration of the photosensitizer strongly correlated with the changes in
      the pulse oximetry data and fluorescence of the backscattering laser, suggesting
      that a clinically appropriate condition could be estimated in real time.
      CONCLUSION: Photodynamic therapy-mediated cardiac lesions might be controllable
      by regulating the photosensitizer concentration, laser output, and irradiation
      time.

PMID- 25564547
TI  - Ablation of perimitral flutter: acute and long-term success of the modified
      anterior line.
AB  - AIMS: The modified anterior line (MAL) is an alternative to the mitral isthmus
      (MI) line for the treatment of perimitral atrial flutter (PMFL). We sought to
      investigate acute and long-term efficacy of this line if routinely used for PMFL.
      METHODS AND RESULTS: The cohort included 77 consecutive patients who underwent
      catheter ablation of PMFL. The anterior line was deployed between the
      anterolateral mitral annulus and the ostium of the left superior pulmonary vein.
      Perimitral atrial flutter was either the presenting arrhythmia after persistent
      atrial fibrillation (AF) ablation (Group 1, n = 42, 54.5%), occurring during AF
      ablation (Group 2, n = 25, 35%) or presenting as primary arrhythmia (Group 3, n =
      8, 10%). Acute success was defined as PMFL termination during MAL deployment with
      demonstration of bidirectional line block. Acute success was achieved in 68 of 77
      patients (88%) without difference between the three groups. In five patients an
      additional MI line was necessary to terminate PMFL and in four patients both
      lines failed to achieve termination. During follow-up (16 +/- 7 months), 38 of 77
      (49%) patients underwent a repeat procedure for a recurrent arrhythmia. During
      reablation, 13 of 38 (34%) patients were identified to have a PMFL recurrence.
      Persistent MAL block was demonstrated in 22 of 38 (58%) patients during the
      repeat ablation. CONCLUSION: The MAL is effective for acute and long-term
      treatment of PMFL. Maintenance of bidirectional MAL block was shown in 58% of
      patients during a repeat ablation.

PMID- 25564538
TI  - Predictors of poor outcome despite recanalization: a multiple regression analysis
      of the NASA registry.
AB  - BACKGROUND: Mechanical thrombectomy with stent-retrievers results in higher
      recanalization rates compared with previous devices. Despite successful
      recanalization rates (Thrombolysis in Cerebral Infarction (TICI) score >=2b) of
      70-83%, good outcomes by 90-day modified Rankin Scale (mRS) score <=2 are
      achieved in only 40-55% of patients. We evaluated predictors of poor outcomes
      (mRS >2) despite successful recanalization (TICI >=2b) in the North American
      Solitaire Stent Retriever Acute Stroke (NASA) registry. METHODS: Logistic
      regression was used to evaluate baseline characteristics and recanalization
      outcomes for association with 90-day mRS score of 0-2 (good outcome) vs 3-6 (poor
      outcome). Univariate tests were carried out for all factors. A multivariable
      model was developed based on backwards selection from the factors with at least
      marginal significance (p<=0.10) on univariate analysis with the retention
      criterion set at p<=0.05. The model was refit to minimize the number of cases
      excluded because of missing covariate values; the c-statistic was a measure of
      predictive power. RESULTS: Of 354 patients, 256 (72.3%) were recanalized
      successfully. Based on 234 recanalized patients evaluated for 90-day mRS score,
      116 (49.6%) had poor outcomes. Univariate analysis identified an increased risk
      of poor outcome for age >=80 years, occlusion site of internal carotid artery
      (ICA)/basilar artery, National Institute of Health Stroke Scale (NIHSS) score
      >=18, history of diabetes mellitus, TICI 2b, use of rescue therapy, not using a
      balloon-guided catheter or intravenous tissue plasminogen activator (IV t-PA),
      and >30 min to recanalization (p<=0.05). In multivariable analysis, age >=80
      years, occlusion site ICA/basilar, initial NIHSS score >=18, diabetes, absence of
      IV t-PA, >=3 passes, and use of rescue therapy were significant independent
      predictors of poor 90-day outcome in a model with good predictive power (c
      index=0.80). CONCLUSIONS: Age, occlusion site, high NIHSS, diabetes, no IV t-PA,
      >=3 passes, and use of rescue therapy are associated with poor 90-day outcome
      despite successful recanalization.

PMID- 25564548
TI  - Determinants of heart rate turbulence in individuals without apparent heart
      disease and in patients with stable coronary artery disease.
AB  - AIMS: To assess the characteristics and determinants of heart rate turbulence
      (HRT) in individuals without any apparent heart disease and in patients with
      coronary artery disease (CAD). METHODS AND RESULTS: Heart rate turbulence
      parameters, turbulence onset (TO), and turbulence slope (TS) were calculated on
      24 h electrocardiogram recordings in 209 individuals without any heart disease
      (group 1) and in 157 CAD patients (group 2). In group 1, only age independently
      predicted abnormal TO (>=0%) [odds ratio (OR), 1.05; P<0.001], while predictors
      of abnormal TS (<=2.5 ms/RR) were age (OR, 0.85; P < 0.001) and hypertension (OR,
      0.19; P = 0.028). In group 2 patients, only age independently predicted TO (OR,
      1.03; P = 0.038), while age (OR, 0.90; P = 0.001) and left ventricular ejection
      fraction (LVEF; OR, 1.07; P = 0.008) predicted TS. Heart rate turbulence values
      were different in groups 1 and 2. Turbulence onset was (mean, standard deviation)
      -1.80 +/- 2.24 vs. -0.73 +/- 1.61%, respectively (P < 0.001), whereas TS was
      (median, interquartile interval) 5.83 (3.25-10.55) vs. 2.93 (1.73-5.81) ms/RR,
      respectively (P < 0.001). Coronary artery disease group, however, did not predict
      abnormal HRT parameters in multivariable analyses, both in the whole population
      and when comparing two subgroups matched for age and gender. Age and (for TS)
      LVEF, indeed, were the only independent predictors of abnormal HRT. CONCLUSIONS:
      Age is a major HRT determinant both in subjects without any apparent heart
      disease and in stable CAD patients. Hypertension and LVEF contribute
      independently to HRT in these two groups, respectively. Coronary artery disease
      group was not by itself associated with abnormal HRT parameters in multivariable
      analyses.

PMID- 25564549
TI  - Injury to the coronary arteries and related structures by implantation of cardiac
      implantable electronic devices.
AB  - Damage to the coronary arteries and related structures from pacemaker and
      implantable cardioverter-defibrillator lead implantation is a rarely reported
      complication that can lead to myocardial infarction and pericardial tamponade
      that may occur acutely or even years later. We summarize the reported cases of
      injury to coronary arteries and related structures and review the causes of
      troponin elevation in the setting of cardiac implantable electronic device
      implantation. 

PMID- 25564550
TI  - The QRS morphology pattern in V5R is a novel and simple parameter for
      differentiating the origin of idiopathic outflow tract ventricular arrhythmias.
AB  - AIMS: There are many reports on the ECG characteristics of idiopathic outflow
      tract ventricular arrhythmias (OT-VAs) to predict their origin. However,
      differentiating near regions using 12-lead ECGs is still complicated. The
      synthesized 18-lead ECG derived from the 12-lead ECG can provide virtual
      waveforms of the right-sided chest leads (V3R, V4R, and V5R) and back leads (V7,
      V8, and V9). The aim of this study was to develop a simple and useful parameter
      for differentiating OT-VA origins using the 18-lead ECG. METHODS AND RESULTS: We
      studied 28 and 73 patients with idiopathic VAs in a pacemapping study and
      validation cohort, respectively. In the pacemapping study, several sites out of
      five different sites were paced in each patient: the anterior and posterior right
      ventricular OT (RVOT-ant and RVOT-post), right and left coronary cusps (RCC and
      LCC), and junction of both cusps (RLJ). The 18-lead ECGs during pacemapping among
      the five sites were compared for establishing a simple parameter to predict VA
      origins. A novel parameter using 18-lead ECGs was tested prospectively in 73
      patients. In the pacemapping study, the dominant QRS morphology pattern in the
      synthesized V5R significantly differed among those sites (RVOT-ant:Rs, RVOT
      post:rS, RCC:QS, RLJ:qR, and LCC:R). The patients in the validation cohort were
      divided into five groups depending on those QRS morphology patterns during VAs in
      the synthesized V5R. Each V5R QRS morphology pattern could predict a precise
      origin of the OT-VAs with an overall accuracy of 75%. CONCLUSION: The QRS
      morphology pattern in V5R was a simple and useful parameter for differentiating
      detailed OT-VA origins.

PMID- 25564551
TI  - Incidence and characteristics of phrenic nerve palsy following pulmonary vein
      isolation with the second-generation as compared with the first-generation
      cryoballoon in 360 consecutive patients.
AB  - AIMS: The second-generation cryoballoon (CB2) with increased surface cooling has
      recently become available. The aim was to investigate the incidence and
      characteristics of phrenic nerve palsy (PNP) during pulmonary vein isolation
      (PVI) using the CB2 as compared with the first-generation balloon (CB1). METHODS
      AND RESULTS: A total of 360 consecutive patients with atrial fibrillation
      underwent PVI with the CB1 (106 patients) or the CB2 (254 patients). Right PN
      function was monitored by continuous stimulation and palpation during septal PV
      ablation. Persistent PNP (present at discharge) occurred in 2.8 and 1.9% (P =
      0.63) of patients, transient PNP (full recovery before discharge) in 5.9 and 3.8%
      (P = 0.41) of patients in the CB2 and CB1 group, respectively. Phrenic nerve
      palsy during ablation at the right inferior PV was observed in 0% (CB1) and 4.3%
      (CB2, P = 0.03) of patients. Using the CB2, a trend of reduced incidence of
      persistent PNP over quartiles of consecutive patients was observed [4.8% (Q1) vs.
      0% (Q4); P = 0.077]. At the culprit PV, PNP occurred after 3.5 +/- 2.1 (CB1) and
      1.1 +/- 0.4 applications (CB2; P = 0.036). Complete recovery of PN function
      occurred after 29 +/- 11 (CB1) and 259 +/- 137 days (CB2; P = 0.004).
      CONCLUSIONS: The rate of transient/persistent PNP associated with the use of the
      CB2 was 5.9 and 2.8%, respectively. Time to restitution of PN function was longer
      using the CB2.

PMID- 25564552
TI  - The impact of frailty in older patients with non-ischaemic cardiomyopathy after
      implantation of cardiac resynchronization therapy defibrillator.
AB  - AIMS: Frailty status impacts the prognosis in older patients with heart disease.
      However, frailty status impact is unknown in patients with non-ischaemic
      cardiomyopathy after cardiac resynchronization therapy (CRT). METHODS AND
      RESULTS: Functional measures of baseline frailty and clinical data were collected
      for all patients with non-ischaemic cardiomyopathy before CRT defibrillator (CRT
      D) implantation. The level of frailty was assessed using the Fried and Walston
      definition. Cox proportional hazard regression models were used to examine the
      association between baseline frailty and decompensated heart failure (HF) at the
      12 months follow-up. The cohort study consisted of 102 patients with a mean age
      of 73 +/- 4 years, 53% of which were male patients. Twenty-nine patients (28%)
      were classified as frail before CRT-D implantation. Twenty-seven patients
      experienced decompensated HF after CRT-D implantation at the 12-month follow-up.
      In the non-frail group, 12 of 73 patients (16.4%) experienced episodes of
      decompensated HF. In contrast, 15 of 29 (55.6%) frail patients experienced higher
      proportions of decompensated HF (P < 0.001). Patients who were frail (hazard
      ratio 4.55, 95% confidence interval 1.726-12.013) were at increased risk for the
      decompensated HF (P for trend = 0.002) compared with those who were not frail.
      CONCLUSION: Frailty is a strong predictor of adverse post-implantation outcome in
      patients with non-ischaemic cardiomyopathy undergoing CRT-D.

PMID- 25564553
TI  - Multiplex ligation-dependent probe amplification copy number variant analysis in
      patients with acquired long QT syndrome.
AB  - AIMS: Thirteen genetic loci map to families with congenital long QT syndrome
      (cLQT) and multiple single nucleotide mutations have been functionally implicated
      in cLQT. Studies have investigated copy number variations (CNVs) in the cLQT
      genes to ascertain their involvement in cLQT. In these studies 3-12% of cLQT
      patients who were mutation negative by all other methods carried CNVs in cLQT
      genes. Prolongation of the QT interval can also be acquired after exposure to
      certain drugs [acquired LQT (aLQT)]. Single nucleotide mutations in cLQT genes
      have also been associated with and functionally implicated in aLQT, but to date
      no studies have explored CNVs as an additional susceptibility factor in aLQT. The
      aim of this study was to explore the contribution of CNVs in determining
      susceptibility to aLQT. METHODS AND RESULTS: In this study we screened the
      commonest cLQT genes (KCNQ1; KCNH2; SCN5A; KCNE1, and KCNE2) in a general
      population of healthy volunteers and in a cohort of subjects presenting with aLQT
      for CNVs using the multiplex ligation-dependent probe amplification method. Copy
      number variants were detected and confirmed in 1 of 197 of the healthy volunteers
      and in 1 of 90 subjects with aLQT. The CNV in the aLQT subject was functionally
      characterized and demonstrated impaired channel function. CONCLUSION: Copy number
      variation is a possible additional risk factor for aLQT and should be considered
      for incorporation into pharmacogenetic screening of LQTS genes in addition to
      mutation detection to improve the safety of medication administration.

PMID- 25564554
TI  - Contact force mapping and voltage thresholds during high-frequency stimulation of
      human cardiac ganglionated plexuses?.
AB  - AIMS: The intrinsic cardiac nervous system consists of ganglionated plexuses
      (GPs) localized epicardially to specific regions of the left atrium (LA). The
      relation between voltage thresholds and endocardial contact force associated with
      autonomic effects during stimulation of GPs has not previously been evaluated.
      METHODS AND RESULTS: Sixteen patients with symptomatic atrial fibrillation (AF)
      underwent mapping of GPs prior to radiofrequency ablation of AF. Pre-acquired
      computed tomographic images were merged with 3D non-fluoroscopic electroanatomic
      mapping of the LA. Using high-frequency stimulation (HFS), the voltage thresholds
      of GPs was obtained while patients received conscious sedation. At each location,
      the contact force measurement from the catheter was correlated with the voltage
      applied during HFS at 5, 10, or 15 V to obtain an autonomic effect, usually
      associated with asystole, or marked bradycardia. There were 192 applications of
      HFS, resulting in GP identification in all patients (mean 3.4 per patient, range
      1-5). During HFS, an autonomic response was significantly more likely to occur at
      10 V as compared with 5 V (P < 0.008). There was no significant relation between
      the measured contact force and the likelihood of obtaining an autonomic response.
      When performing HFS at 15 V, a sudden overshoot with maximal values of contact
      force of up to 100 g was also observed. High-frequency stimulation was well
      tolerated, without associated adverse events. CONCLUSION: An autonomic response
      during HFS was significantly more likely to occur at 10 V as compared with 5 V.
      Although the GPs are epicardial structures, significant contact force was not
      required for their localization.

PMID- 25564556
TI  - Overcoming the challenges of anticoagulation in adults with congenital heart
      disease.

PMID- 25564555
TI  - Understanding the biochemical basis of temperature-induced lipid pathway
      adjustments in plants.
AB  - Glycerolipid biosynthesis in plants proceeds through two major pathways
      compartmentalized in the chloroplast and the endoplasmic reticulum (ER). The
      involvement of glycerolipid pathway interactions in modulating membrane
      desaturation under temperature stress has been suggested but not fully explored.
      We profiled glycerolipid changes as well as transcript dynamics under suboptimal
      temperature conditions in three plant species that are distinctively different in
      the mode of lipid pathway interactions. In Arabidopsis thaliana, a 16:3 plant,
      the chloroplast pathway is upregulated in response to low temperature, whereas
      high temperature promotes the eukaryotic pathway. Operating under a similar
      mechanistic framework, Atriplex lentiformis at high temperature drastically
      increases the contribution of the eukaryotic pathway and correspondingly
      suppresses the prokaryotic pathway, resulting in the switch of lipid profile from
      16:3 to 18:3. In wheat (Triticum aestivum), an 18:3 plant, low temperature also
      influences the channeling of glycerolipids from the ER to chloroplast. Evidence
      of differential trafficking of diacylglycerol moieties from the ER to chloroplast
      was uncovered in three plant species as another layer of metabolic adaptation
      under temperature stress. We propose a model that highlights the predominance and
      prevalence of lipid pathway interactions in temperature-induced lipid
      compositional changes. 

PMID- 25564557
TI  - Pregnancy risks in women with pre-existing coronary artery disease, or following
      acute coronary syndrome.
AB  - OBJECTIVE: The objective of this study was to determine outcomes in pregnant
      women with pre-existing coronary artery disease (CAD) or following an acute
      coronary syndrome (ACS) including myocardial infarction (MI). BACKGROUND: The
      physiological changes of pregnancy can contribute to myocardial ischaemia. The
      pregnancy risk for women with pre-established CAD or a history of ACS/MI is not
      well studied. METHODS: This was a retrospective multicentre study. Adverse
      maternal cardiac, obstetric and fetal/neonatal events were examined. The primary
      outcome was a composite endpoint of cardiac arrest, ACS/MI, ventricular
      arrhythmia or congestive heart failure. The prevalence of new or progressive
      angina during pregnancy was also examined. RESULTS: Fifty pregnancies in 43 women
      (mean age 35+/-5 years) were included. Coronary atherosclerosis (40%) and
      coronary thrombus (36%) were the most common underlying diagnoses. The primary
      outcome occurred in 10% (5/50) of pregnancies and included one maternal death
      secondary to cardiac arrest. Other events included ACS/MI (3/50) and heart
      failure (1/50). New or progressive angina occurred in 18% of pregnancies.
      Ischaemic complications of any type (new or progressive angina, ACS/MI,
      ventricular arrhythmia, cardiac arrest) occurred more commonly in women with
      coronary atherosclerosis compared with those without (50% vs 10%, p=0.003). A
      high rate of adverse obstetric (16%) and fetal/neonatal (30%) events was
      observed. CONCLUSIONS: Pregnant women with pre-existing CAD or ACS/MI before
      pregnancy are at increased risk of adverse events during pregnancy. Those with
      coronary atherosclerosis are at highest risk of adverse maternal cardiac events
      due to myocardial ischaemia during pregnancy.

PMID- 25564558
TI  - Long-term maternal atherosclerotic morbidity in women with pre-eclampsia.
AB  - OBJECTIVE: To investigate whether severe and recurrent pre-eclampsia increase the
      risk for long-term maternal atherosclerotic disease. STUDY DESIGN: A population
      based study compared the incidence of long-term atherosclerotic morbidity in a
      cohort of women who delivered in the years 1988-2012. The exposure variable was
      pre-eclampsia. Mean follow-up duration was 11.2 years. Kaplan-Meier survival
      curves were used to estimate cumulative incidence of simple, complex (ie, angina
      pectoris and congestive heart failure, respectively) cardiovascular-related and
      renal-related hospitalisations. Cox proportional hazards models were used to
      estimate the adjusted HRs for cardiovascular and renal morbidity. RESULTS: During
      the study, 96 370 patients met the inclusion criteria; 7824 (8.1%) in patients
      who were diagnosed at least once with pre-eclampsia. Patients with pre-eclampsia
      had higher rates of cardiovascular morbidity including cardiac non-invasive (OR
      1.4; 95% CI 1.1 to 1.7; p=0.005) and invasive diagnostic procedures (OR 1.7; 95%
      CI 1.2 to 2.3; p=0.001), simple (OR 1.5; 95% CI 1.2 to 1.8; p=0.001), as well as
      complex cardiovascular events (OR 2.4; 95% CI 2.2 to 2.8; p=0.001) and renal (OR
      3.7; 95% CI 2.2 to 6.0; p=0.001) hospitalisations. A significant linear
      association was noted between the severity of pre-eclampsia (no pre-eclampsia,
      mild pre-eclampsia, severe pre-eclampsia and eclampsia) and cardiovascular (2.7%
      vs 4.5% vs 5.2% vs 5.7%, respectively; p=0.001), as well as renal disease (0.1%
      vs 0.2% vs 0.5% vs 1.1%, respectively; p=0.001). Likewise, a linear association
      was found between the number of previous pregnancies with pre-eclampsia (no pre
      eclampsia, one event and >=2 events of pre-eclampsia) and risk for future simple
      cardiovascular disease (1.2% vs 1.6% vs 2.2%, respectively; p=0.001), complex
      cardiovascular disease (1.3% vs 2.7% vs 4.6%, respectively; p=0.001) and total
      cardiovascular hospitalisations (2.7% vs 4.4% vs 6.0%, respectively; p=0.001).
      Using a Kaplan-Meier survival curve, patients with pre-eclampsia had
      significantly higher cumulative incidence of atherosclerotic-related
      hospitalisations. In a Cox proportional hazards model, adjusted for confounders
      such as maternal age, parity, diabetes mellitus and obesity, pre-eclampsia
      remained independently associated with atherosclerotic hospitalisations.
      CONCLUSIONS: Previous pregnancy with pre-eclampsia is an independent risk factor
      for long-term maternal atherosclerotic morbidity. The risk is more substantial
      for patients with severe and recurrent episodes of pre-eclampsia.

PMID- 25564560
TI  - A tribute to Margaret W. Thompson.

PMID- 25564559
TI  - A heteromeric membrane-bound prenyltransferase complex from hop catalyzes three
      sequential aromatic prenylations in the bitter acid pathway.
AB  - Bitter acids (alpha and beta types) account for more than 30% of the fresh weight
      of hop (Humulus lupulus) glandular trichomes and are well known for their
      contribution to the bitter taste of beer. These multiprenylated chemicals also
      show diverse biological activities, some of which have potential benefits to
      human health. The bitter acid biosynthetic pathway has been investigated
      extensively, and the genes for the early steps of bitter acid synthesis have been
      cloned and functionally characterized. However, little is known about the
      enzyme(s) that catalyze three sequential prenylation steps in the beta-bitter
      acid pathway. Here, we employed a yeast (Saccharomyces cerevisiae) system for the
      functional identification of aromatic prenyltransferase (PT) genes. Two PT genes
      (HlPT1L and HlPT2) obtained from a hop trichome-specific complementary DNA
      library were functionally characterized using this yeast system. Coexpression of
      codon-optimized PT1L and PT2 in yeast, together with upstream genes, led to the
      production of bitter acids, but no bitter acids were detected when either of the
      PT genes was expressed by itself. Stepwise mutation of the aspartate-rich motifs
      in PT1L and PT2 further revealed the prenylation sequence of these two enzymes in
      beta-bitter acid biosynthesis: PT1L catalyzed only the first prenylation step,
      and PT2 catalyzed the two subsequent prenylation steps. A metabolon formed
      through interactions between PT1L and PT2 was demonstrated using a yeast two
      hybrid system, reciprocal coimmunoprecipitation, and in vitro biochemical assays.
      These results provide direct evidence of the involvement of a functional
      metabolon of membrane-bound prenyltransferases in bitter acid biosynthesis in
      hop.

PMID- 25564563
TI  - Development of an expert professional curriculum for antimicrobial pharmacists in
      the UK.
AB  - The role of antimicrobial pharmacists has changed considerably over the past 15
      years. We describe here the development and ratification of a new expert
      professional curriculum to guide the training and development of antimicrobial
      specialist pharmacists. The curriculum has been developed by the UK Clinical
      Pharmacy Association Pharmacy Infection Network and endorsed by the Royal
      Pharmaceutical Society as a tool to support pharmacists in meeting the
      requirements for joining the Royal Pharmaceutical Society Faculty. This new
      resource has also been endorsed by PHE, the Scottish Antimicrobial Prescribing
      Group and the BSAC, and will support antimicrobial pharmacists in delivery of
      antimicrobial stewardship, which will in turn help the fight against
      antimicrobial resistance. 

PMID- 25564562
TI  - Micafungin twice weekly as antifungal prophylaxis in paediatric patients at high
      risk for invasive fungal disease.
AB  - BACKGROUND: Current guidelines recommend antifungal prophylaxis for children at
      high risk for invasive fungal disease (IFD), but the use of polyenes and
      triazoles may not be feasible in some patients due to toxicities and drug-drug
      interactions. Micafungin is well tolerated, with intravenous daily dosing being
      the current standard. Recent reports indicate safety and efficacy of intermittent
      dosing of micafungin. METHODS: We analysed safety, efficacy and micafungin serum
      concentrations of children at high risk for IFD receiving prophylactic micafungin
      between 3 and 4 mg/kg twice weekly. All children were intolerant or had
      contraindications to polyenes and triazoles. RESULTS: A total of 21 children
      (median age = 9 years) at high risk for IFD were included in the analysis. No
      significant clinical adverse event occurred, and end of treatment values of
      parameters of renal and hepatic function in serum were not different from
      baseline. Proven or probable breakthrough IFD did not occur in any of the
      patients. In 9 out of 11 patients in whom plasma micafungin concentrations were
      assessed, the first trough concentration exceeded 150 ng/mL, a concentration
      proposed to be effective for prophylaxis. CONCLUSIONS: Our data indicate that
      micafungin administered twice weekly at a dosage of 3-4 mg/kg of bodyweight could
      be a convenient, safe and efficient alternative for antifungal prophylaxis in
      children at high risk for IFD.

PMID- 25564561
TI  - The kinetochore protein, CENPF, is mutated in human ciliopathy and microcephaly
      phenotypes.
AB  - BACKGROUND: Mutations in microtubule-regulating genes are associated with
      disorders of neuronal migration and microcephaly. Regulation of centriole length
      has been shown to underlie the pathogenesis of certain ciliopathy phenotypes.
      Using a next-generation sequencing approach, we identified mutations in a novel
      centriolar disease gene in a kindred with an embryonic lethal ciliopathy
      phenotype and in a patient with primary microcephaly. METHODS AND RESULTS: Whole
      exome sequencing data from a non-consanguineous Caucasian kindred exhibiting mid
      gestation lethality and ciliopathic malformations revealed two novel non
      synonymous variants in CENPF, a microtubule-regulating gene. All four affected
      fetuses showed segregation for two mutated alleles [IVS5-2A>C, predicted to
      abolish the consensus splice-acceptor site from exon 6; c.1744G>T, p.E582X]. In a
      second unrelated patient exhibiting microcephaly, we identified two CENPF
      mutations [c.1744G>T, p.E582X; c.8692 C>T, p.R2898X] by whole exome sequencing.
      We found that CENP-F colocalised with Ninein at the subdistal appendages of the
      mother centriole in mouse inner medullary collecting duct cells. Intraflagellar
      transport protein-88 (IFT-88) colocalised with CENP-F along the ciliary axonemes
      of renal epithelial cells in age-matched control human fetuses but did not in
      truncated cilia of mutant CENPF kidneys. Pairwise co-immunoprecipitation assays
      of mitotic and serum-starved HEKT293 cells confirmed that IFT88 precipitates with
      endogenous CENP-F. CONCLUSIONS: Our data identify CENPF as a new centriolar
      disease gene implicated in severe human ciliopathy and microcephaly related
      phenotypes. CENP-F has a novel putative function in ciliogenesis and cortical
      neurogenesis.

PMID- 25564564
TI  - Activity of temocillin in a murine model of urinary tract infection due to
      Escherichia coli producing or not producing the ESBL CTX-M-15.
AB  - OBJECTIVES: Temocillin is a 6alpha-methoxy derivative of ticarcillin that is
      resilient to ESBLs. Prospective data about its in vivo activity remain scarce.
      Our aims were: (i) to evaluate the activity of temocillin in a urinary tract
      infection (UTI) model due to ESBL-producing Escherichia coli and compare it with
      that of imipenem; and (ii) to define in vivo susceptibility breakpoints. METHODS:
      Mice were infected with a susceptible E. coli CFT073-RR or its transconjugant
      (CFT073-RR Tc) harbouring a blaCTX-M-15-carrying plasmid, using an ascending UTI
      model. Therapeutic regimens were chosen in order to reproduce percentage of time
      of free drug concentrations above MIC (fT>MIC) obtained in humans with standard
      regimens of temocillin (200 mg/kg every 2 h for 2 g every 12 h) or imipenem (100
      mg/kg every 2 h for 1 g every 8 h). Additional regimens of temocillin (200 mg/kg
      every 4 and 6 h) with reduced fT>MIC were studied. RESULTS: MICs of temocillin
      and imipenem were 4/8 and 0.5/0.5 mg/L, for CFT073-RR and CFT073-RR Tc,
      respectively. In vivo, when given every 2 h (fT>MIC = 82% and 70%), temocillin
      was bactericidal and as effective as imipenem in kidneys against both strains
      without selecting resistant mutants. Temocillin remained active even when given
      every 4 h, generating an fT>MIC of 41% and 35%, which corresponded to a
      breakpoint of 16 mg/L in humans with the standard regimen. CONCLUSIONS: Our
      observations support the consideration of a standard regimen of temocillin as an
      alternative to carbapenems for the treatment of UTI due to CTX-M-producing E.
      coli strains with an MIC of 16 mg/L or less.

PMID- 25564566
TI  - New developments in electron microscopy for serial image acquisition of neuronal
      profiles.
AB  - Recent developments in electron microscopy largely automate the continuous
      acquisition of serial electron micrographs (EMGs), previously achieved by
      laborious manual serial ultrathin sectioning using an ultramicrotome and
      ultrastructural image capture process with transmission electron microscopy. The
      new systems cut thin sections and capture serial EMGs automatically, allowing for
      acquisition of large data sets in a reasonably short time. The new methods are
      focused ion beam/scanning electron microscopy, ultramicrotome/serial block-face
      scanning electron microscopy, automated tape-collection ultramicrotome/scanning
      electron microscopy and transmission electron microscope camera array. In this
      review, their positive and negative aspects are discussed. 

PMID- 25564568
TI  - Clinical Cancer Research: the 20th anniversary.

PMID- 25564565
TI  - Early agr activation correlates with vancomycin treatment failure in multi
      clonotype MRSA endovascular infections.
AB  - OBJECTIVES: Persistent MRSA infections are especially relevant to endovascular
      infections and correlate with suboptimal outcomes. However, the virulence
      signatures of Staphylococcus aureus that drive such persistence outcomes are not
      well defined. In the current study, we investigated correlations between
      accessory gene regulator (agr) activation and the outcome of vancomycin treatment
      in an experimental model of infective endocarditis (IE) due to MRSA strains with
      different agr and clonal complex (CC) types. METHODS: Twelve isolates with the
      four most common MRSA CC and agr types (CC5-agr II, CC8-agr I, CC30-agr III and
      CC45-agr I) were evaluated for heterogeneous vancomycin-intermediate S. aureus
      (hVISA), agr function, agrA and RNAIII transcription, agr locus sequences,
      virulence and response to vancomycin in the IE model. RESULTS: Early agr RNAIII
      activation (beginning at 2 h of growth) in parallel with strong delta-haemolysin
      production correlated with persistent outcomes in the IE model following
      vancomycin therapy. Importantly, such treatment failures occurred across the
      range of CC/agr types studied. In addition, these MRSA strains: (i) were
      vancomycin susceptible in vitro; (ii) were not hVISA or vancomycin tolerant; and
      (iii) did not evolve hVISA phenotypes or perturbed delta-haemolysin activity in
      vivo following vancomycin therapy. Moreover, agr locus sequence analyses revealed
      no common point mutations that correlated with either temporal RNAIII
      transcription or vancomycin treatment outcomes, encompassing different CC and agr
      types. CONCLUSIONS: These data suggest that temporal agr RNAIII activation and
      agr functional profiles may be useful biomarkers to predict the in vivo
      persistence of endovascular MRSA infections despite vancomycin therapy.

PMID- 25564569
TI  - New strategies in renal cell carcinoma: targeting the genetic and metabolic basis
      of disease.
AB  - The development of new forms of treatment of advanced renal cell carcinoma over
      the past two decades has been primarily focused on targeting the VHL/HIF pathway.
      The recent identification of mutations of chromatin-remodeling genes in clear
      cell renal carcinoma (ccRCC), of genomic heterogeneity, and of a Warburg-like
      metabolic phenotype in advanced disease has had a profound effect on our
      understanding of the evolution of ccRCC and on potential approaches to
      personalized therapy. Early approaches to therapy for patients with advanced type
      I papillary RCC that have centered around the MET/HGF pathway will expand as more
      genomic information becomes available. Sporadic and familial type II papillary
      renal cell carcinoma are characterized by enhanced aerobic glycolysis and share
      an antioxidant response phenotype. In fumarate hydratase-deficient RCC, fumarate
      induced succination of KEAP1 activates Nrf2 signaling. CUL3 and Nrf2 mutations as
      well as an Nrf2 activation phenotype are found in sporadic type II papillary RCC.
      Therapeutic approaches designed to target the Nrf2 pathway as well as to impair
      blood flow and glucose delivery in these cancers that are highly dependent on a
      robust tumor vasculature and on ready availability of glucose for energy
      production and glycolysis are in development.

PMID- 25564571
TI  - Development of a prognostic genetic signature to predict the metastatic risk
      associated with cutaneous melanoma.
AB  - PURPOSE: The development of a genetic signature for the identification of high
      risk cutaneous melanoma tumors would provide a valuable prognostic tool with
      value for stage I and II patients who represent a remarkably heterogeneous group
      with a 3% to 55% chance of disease progression and death 5 years from diagnosis.
      EXPERIMENTAL DESIGN: A prognostic 28-gene signature was identified by analysis of
      microarray expression data. Primary cutaneous melanoma tumor tissue was evaluated
      by RT-PCR for expression of the signature, and radial basis machine (RBM)
      modeling was performed to predict risk of metastasis. RESULTS: RBM analysis of
      cutaneous melanoma tumor gene expression reports low risk (class 1) or high risk
      (class 2) of metastasis. Metastatic risk was predicted with high accuracy in
      development (ROC = 0.93) and validation (ROC = 0.91) cohorts of primary cutaneous
      melanoma tumor tissue. Kaplan-Meier analysis indicated that the 5-year disease
      free survival (DFS) rates in the development set were 100% and 38% for predicted
      classes 1 and 2 cases, respectively (P < 0.0001). DFS rates for the validation
      set were 97% and 31% for predicted classes 1 and 2 cases, respectively (P <
      0.0001). Gene expression profile (GEP), American Joint Committee on Cancer stage,
      Breslow thickness, ulceration, and age were independent predictors of metastatic
      risk according to Cox regression analysis. CONCLUSIONS: The GEP signature
      accurately predicts metastasis risk in a multicenter cohort of primary cutaneous
      melanoma tumors. Preliminary Cox regression analysis indicates that the signature
      is an independent predictor of metastasis risk in the cohort presented.

PMID- 25564570
TI  - Tadalafil augments tumor specific immunity in patients with head and neck
      squamous cell carcinoma.
AB  - PURPOSE: To determine if phosphodiesterase 5 (PDE5) inhibitors can augment immune
      function in patients with head and neck cancer through inhibition of myeloid
      derived suppressor cells (MDSC). EXPERIMENTAL DESIGN: We performed a randomized,
      prospective, double blinded, placebo controlled, phase II clinical trial to
      determine the in vivo effects of systemic PDE5 inhibition on immune function in
      patients with head and neck squamous cell carcinoma (HNSCC). RESULTS: Tadalafil
      augmented immune response, increasing ex vivo T-cell expansion to a mean 2.4-fold
      increase compared with 1.1-fold in control patients (P = 0.01), reducing
      peripheral MDSC numbers to mean 0.81-fold change compared with a 1.26-fold change
      in control patients (P = 0.001), and increasing general immunity as measured by
      delayed type hypersensitivity response (P = 0.002). Tumor-specific immunity in
      response to HNSCC tumor lysate was augmented in tadalafil-treated patients (P =
      0.04). CONCLUSIONS: These findings demonstrate that tadalafil augments general
      and tumor-specific immunity in patients with HNSCC and has therapeutic potential
      in HNSCC. Evasion of immune surveillance and suppression of systemic and tumor
      specific immunity is a significant feature of head and neck cancer development.
      This study demonstrates that a PDE5 inhibitor, tadalafil, can reverse tumor
      specific immune suppression in patients with head and neck cancer, with potential
      for therapeutic application.

PMID- 25564573
TI  - Diffusion-weighted MRI for lymphoma staging--letter.

PMID- 25564572
TI  - Activation of IL6/IGFIR confers poor prognosis of HBV-related hepatocellular
      carcinoma through induction of OCT4/NANOG expression.
AB  - PURPOSE: To unravel the role of interleukin (IL)-6 and insulin-like growth factor
      (IGF)-I receptor (IGFIR) in expressing stemness-related properties and to
      evaluate the prognostic values of pluripotent transcription factor OCT4/NANOG,
      and IGFIR in hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Serum levels of
      IL6 were detected using ELISA assays (n = 120). The effects of IL6/IGFI on
      stemness expression in HCC were examined using OCT4/NANOG promoter luciferase
      reporter, RNA interference, secondary sphere formation, side population, and
      xenograft animal models. The OCT4/NANOG protein and phospho-IGFI receptor (p
      IGFIR) in tissues were detected by Western blotting (n = 8) and
      immunohistochemical staining (n = 85). OCT4, NANOG, and IGFIR expression levels
      in tissues (n = 191) were analyzed by real-time qRT-PCR and was correlated with
      early tumor recurrence using the Kaplan-Meier survival analysis. RESULTS: A high
      positive correlation between the expression levels of OCT4/NANOG and IGFIR/p
      IGFIR in human HCC tissues was observed. The concurrent expression of
      OCT4/NANOG/IGFIR was mostly confined to hepatitis B virus (HBV)-related HCC (HBV
      HCC) and was significantly correlated with early tumor recurrence. High serum
      levels of IL6 were significantly correlated with high OCT4/NANOG expression. IL6
      stimulated an autocrine IGFI/IGFIR expression STAT3 dependently, which stimulated
      stemness-related properties in both the cell lines and the xenografted mouse
      tumors. The inhibition of IGFIR activation by either RNA interference or by
      treatment with the inhibitor picropodophyllin (PPP) significantly suppressed the
      IL6-induced stemness-related properties both in vitro and in vivo. CONCLUSIONS:
      The expression of pluripotency-related genes is associated with early tumor
      recurrence and is regulated by IL6-induced IGF/IGFIR activation, particularly in
      HBV-HCC.

PMID- 25564574
TI  - Diffusion-weighted MRI for lymphoma staging--response.

PMID- 25564575
TI  - Simultaneous quantitation of amphetamines and opiates in human hair by liquid
      chromatography-tandem mass spectrometry.
AB  - In this study, an incubation, solid-phase extraction (SPE) and LC-MS-MS procedure
      was developed, validated and used for simultaneous analysis of amphetamine (AP),
      methamphetamine (MA), morphine (MOR), codeine (COD), 6-acetylmorphine (6-AM) and
      6-acetylcodeine (6-AC) in hair. Hair samples were initially cut into sections,
      washed with dichloromethane, then sonicated in a methanol-trifluoroacetic acid
      mixture. The resulting solutions were processed with a SPE procedure before
      undergoing LC-MS-MS analysis. Mass spectrometric analysis was performed in
      positive-ion, multiple reactions monitoring (MRM) mode, using appropriate
      collision energy for each selected precursor ion. The overall protocol, when
      applied to the analysis of hair (50 mg) samples fortified with 100-10,000 pg/mg
      of the analytes, was found to achieve 55.5-74.6% recovery of the six analytes
      with the following analytical parameters: (i) intra- and interday
      precision/accuracy data for the six analytes in the 1.6-7.6%/-6.0-12.8% and 1.3
      6.6%/-6.9-9.3% ranges, respectively; (ii) r(2) > 0.998 for all six analytes and
      (iii) LOD 2 pg/mg for AP and MA, and 8 pg/mg for MOR, COD, 6-AM and 6-AC; LOQ 10
      pg/mg for all six analytes. This method was then utilized to (i) analyze hair
      samples collected from 86 self-reported drug users and (ii) evaluate the
      deposition pattern of drugs in head hairs from four female MA and heroin users in
      a rehabilitation facility. This relatively simple protocol was found superior
      over the GC-MS methods we have previously developed and utilized in our
      laboratory for the analysis of these six analytes. 

PMID- 25564576
TI  - Risk factors for urinary retention following minor thoracic surgery.
AB  - OBJECTIVES: Our goals were (i) to identify the incidence and risk factors of
      postoperative urinary retention in minor thoracic surgery patients and (ii) to
      develop a scoring system to predict postoperative urinary retention in these
      patients. METHODS: Two hundred and ninety-two consecutive patients who underwent
      thoracic surgery without a pre- or intraoperative indwelling urinary catheter
      under general anaesthesia were used to identify the risk factors of postoperative
      urinary retention (post-void residual urine >200 ml) and to develop the scoring
      system predicting the incidence of this complication. We investigated past
      history, type of operation, operation time, amount of administered intravenous
      fluids, medications used perioperatively as well as demographic data. RESULTS:
      The incidence rate of postoperative urinary retention was 11.6% (34/292).
      Independent risk factors and their scores were the following: age above 40 years
      (P < 0.001; two points); male (P = 0.002; one point); diabetes mellitus (P =
      0.002; one point) and lung resection (P < 0.001; two points). The cut-off value
      for a model predicting postoperative urinary retention was five points (C-index =
      0.88; 95% confidence interval: 0.83-0.94), with 73% sensitivity and 90%
      specificity. CONCLUSIONS: In minor thoracic surgery patients, special attention
      should be paid to detect postoperative urinary retention in those with the
      following characteristics: age over 40 years, male gender, history of diabetes
      mellitus and candidates for lung resection. The use of the developed scoring
      system may help in identifying those high-risk patients who need more aggressive
      management to prevent bladder overdistension and associated urinary
      complications.

PMID- 25564577
TI  - Primary extraskeletal myxoid chondrosarcoma of pulmonary arteries: a rare mimic
      of acute pulmonary thromboembolism.
AB  - Primary extraskeletal myxoid chondrosarcoma of the pulmonary arteries is a very
      rare entity. Multimodality imaging reports on this entity are few. Myxoid
      chondrosarcoma is characterized by chondroid and neurogenic differentiation in
      extraskeletal locations. These tumours represent fewer than 2.5% of all soft
      tissue sarcomas, and are most commonly found in the lower extremities, limb
      girdles, distal extremities and trunk. We report an unusual case of a 31-year old
      man with histopathologically proven extraskeletal myxoid chondrosarcoma of the
      pulmonary arteries mimicking acute pulmonary thromboembolism. 

PMID- 25564578
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration is a sensitive
      method to evaluate patients who should not undergo pulmonary metastasectomy?.
AB  - OBJECTIVES: Pulmonary metastasectomy is considered an effective treatment in
      selected patients with extrapulmonary cancer and oligometastatic disease. We know
      that the presence of mediastinal lymph node metastases reduces survival
      significantly, but the mediastinum is rarely evaluated before metastasectomy in
      these patients. We prospectively evaluated how endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) could identify metastases to the
      mediastinal lymph nodes in patients referred for pulmonary metastasectomy.
      METHODS: All patients with extrapulmonary cancer and oligometastatic disease
      confined to the lungs on positron emission tomography-computed tomography, and
      who were considered eligible for pulmonary metastasectomy, routinely underwent
      EBUS-TBNA of the mediastinal lymph nodes. If EBUS-TBNA did not reveal malignant
      spread, the patient subsequently underwent pulmonary metastasectomy with
      systematic sampling of mediastinal lymph nodes for histological evaluation.
      RESULTS: One hundred and three eligible patients were referred for EBUS-TBNA
      during a 4-year period. The primary cancers were located in the colon/rectum (n =
      64), kidney (n = 16) and other sites (n = 23). EBUS-TBNA sampled 248 lymph nodes
      and adequate cytology was obtained in 93 patients (90%). EBUS-TBNA found lymph
      node metastases in 17 patients (16.5%) and during subsequent pulmonary
      metastasectomy in the remaining 86 patients 1 (1.0%) had a lymph node metastasis.
      The sensitivity, specificity, NPV and PPV of EBUS-TBNA for diagnosis of
      mediastinal lymph node metastasis were 94.4, 100, 98.8 and 100%, respectively.
      CONCLUSIONS: EBUS-TBNA is a sensitive minimally invasive modality for evaluation
      of mediastinal lymph node metastases in patients with oligometastatic pulmonary
      disease. It allows surgeons to select patients who will not benefit from
      pulmonary metastasectomy.

PMID- 25564579
TI  - Hybrid branch pulmonary artery stent placement in adults with congenital heart
      disease.
AB  - OBJECTIVES: Valuable treatment modalities for branch pulmonary artery (BPA)
      stenoses are surgical patch angioplasty, percutaneous BPA stenting and hybrid
      stent placement. The purpose of this study was to report our institutional
      experience with hybrid stent placement to relieve BPA stenoses. METHODS: Between
      August 2007 and May 2014, 7 adults (5 females) with congenital heart disease
      (CHD) had elective intraoperative BPA stent placement. All 7 patients had
      undergone previous surgery [6 tetralogy of Fallot repairs and 1 arterial switch
      operation for transposition of the great arteries (TGAs)]. A total of 7 stents (4
      right pulmonary artery, 3 left pulmonary artery) were implanted under direct
      vision, concomitant with a pulmonary homograft implantation (tetralogy of Fallot
      patients), or because percutaneous stenting was not feasible (TGA patient).
      Retrospective analysis of clinical data, procedural details and outcomes was
      performed. RESULTS: Overall, the mean age was 35 +/- 7.2 years. Stent
      implantation was successful in all procedures. The mean postinflation stent
      diameter was 13.3 +/- 2.0 mm. No stent migration, fracture, stent thrombosis,
      reintervention or deaths occurred. In 1 case the procedure was complicated by a
      right pulmonary artery tear just distal to the stent which was repaired by
      surgical patch angioplasty. At a mean follow-up of 55.6 +/- 26 months no patient
      required catheter reintervention or surgery. Echocardiography (mean follow-up
      47.1 +/- 22 months), MRI (mean follow-up 43.8 +/- 37 months) and CT data (mean
      follow-up 14.8 +/- 10 months) demonstrate a BPA diameter increment from a mean
      5.57 +/- 2.29 to 10.71 +/- 2.56 mm. CONCLUSIONS: Hybrid intraoperative BPA stent
      placement is safe and effective and can be used as an alternative for surgical
      patch angioplasty or if percutaneous BPA stenting is not feasible. Short- to mid
      term results are good.

PMID- 25564580
TI  - Pectus excavatum in relief from Ancient Egypt (dating back to circa 2400 BC).
AB  - Pectus excavatum is one of the most common congenital deformities of the chest
      wall. The aim of the study was to analyse 621 artefacts (reliefs, sculptures,
      paintings) from Ancient Egypt in terms of anatomical defects of the chest. The
      team which analysed artefacts consisted of historians of medicine and thoracic
      surgeons. The researchers found a relief, depicting a man with an abnormal shape
      of the chest. The relief was from Niankhkhnum and Khnumhotep mastaba and dates
      back to circa 2400 BC. The authors think it is possible that the relief may
      represent a pectus excavatum deformity and believe the image will open up debate
      on the occurrence of this deformity in ancient times. 

PMID- 25564581
TI  - Healthcare improvement.

PMID- 25564582
TI  - Histiocytic necrotising lymphadenitis (Kikuchi-Fujimoto disease) of axillary
      lymph nodes.
AB  - Kikuchi-Fujimoto disease (KFD) or histiocytic necrotising lymphadenitis is a rare
      entity, occurring most commonly in young Asian adults. KFD is characterised by
      fever with tender lymph node enlargement. The cervical group of lymph nodes is
      most commonly involved, and the diagnosis is conclusively made by lymph node
      biopsy and histopathology. KFD is a self-limiting condition, which usually
      resolves over 1-4 months. Symptomatic treatment with antipyretics and/or non
      steroidal anti-inflammatory drugs is recommended. Here we describe an uncommon
      presentation of KFD in a young woman in which only the axillary lymph nodes were
      enlarged. 

PMID- 25564583
TI  - Atrio-oesophageal fistula after transcatheter radiofrequency ablation.
AB  - A 68-year-old woman presented 3 weeks following unsuccessful transcatheter
      radiofrequency ablation (TcRFA) for treatment of her chronic atrial fibrillation.
      Neurological signs manifested on day 2 of admission with generalised tonic-clonic
      seizures and reduced Glasgow Coma Score. She was treated for presumed central
      nervous system (CNS) infection, intubated and transferred to the intensive care
      unit. CT of the head showed bilateral oedema secondary to acute embolic stroke.
      Blood cultures grew Streptococcus viridans, and lumbar puncture findings were
      consistent with CNS infection. Echocardiography showed only a septostomy puncture
      from the atrial fibrillation ablation procedure. Thoracic CT demonstrated air in
      the left atrium, consistent with the diagnosis of atrio-oesophageal fistula, a
      rarely reported iatrogenic complication of TcRFA. MRI of the head showed
      significant neurological injury with innumerable embolic infarcts. After
      discussion with her family regarding the significant neurological insult, and
      with no signs of any clinical improvement, the patient died on day 8 of
      admission. 

PMID- 25564584
TI  - A long-term follow-up of residual mass neuroblastoma in a patient with cystic
      fibrosis.
AB  - PURPOSE: To report a long-term follow-up of a young woman affected by cystic
      fibrosis (CF) with a residual retroperitoneal mass of neuroblastoma (NBL) after
      treatment. CASE REPORT: We reviewed the patient's database and analysed a 20-year
      follow-up by considering pulmonary exacerbation, nutritional condition, pulmonary
      function (forced expiratory volume in 1 s), microbiological data and residual
      retroperitoneal mass volume. We observed stable pulmonary and nutritional
      conditions. No variation was found in the residual retroperitoneal mass volume.
      DISCUSSION: We report this case of a patient with CF with previous NBL because
      such a long time of follow-up of a NBL with a stable retroperitoneal remaining
      tumour is uncommon and needs to be reported. Multidisciplinary management has
      been crucial in this case because of the presence of concomitant diseases and
      consequently, differential diagnosis challenges.

PMID- 25564585
TI  - Low serum free thyroxine level in a girl with McCune-Albright syndrome.
AB  - A 17-year-old girl with McCune-Albright syndrome (MAS) was suspected of having
      central hypothyroidism based on an inappropriately normal thyroid-stimulating
      hormone (TSH) and low free thyroxine (fT4). She was clinically euthyroid and her
      pituitary appeared normal on MRI. Treatment of hypothyroidism with levothyroxine
      resulted in suppression of TSH with a low fT4 and high free triiodothyronine
      (fT3) concentration and hence iatrogenic hyperthyroidism was diagnosed. After
      discontinuation of levothyroxine, the TSH and fT3 normalised while fT4 remained
      low. Increased conversion of thyroxine (T4) to triiodothyronine (T3) can be part
      of MAS. Therefore, fT3 and fT4 should both be measured when evaluating thyroid
      function in patients with MAS. 

PMID- 25564586
TI  - Splenic abscess as a potential initial manifestation of quiescent infective
      endocarditis in a patient with bronchopneumonia.
AB  - A 78-year-old woman presented to the acute medical unit with a productive cough,
      dyspnoea and decreased appetite of 4 days duration. Initial assessment supported
      a diagnosis of right-sided community-acquired pneumonia and she was started on
      antibiotics. In view of the clinical finding of splenomegaly, she had an
      ultrasound and, subsequently, a CT of the abdomen, which revealed a large splenic
      abscess. Pending cultures from a sample obtained from percutaneous drainage of
      the abscess, she was started on intravenous meropenem. The initial echocardiogram
      did not suggest any evidence of endocarditis. The pus drained from the abscess on
      cultures was subsequently positive for Staphylococcus aureus. An MRI of the spine
      excluded discitis as a source of infection. Owing to a high index of clinical
      suspicion a repeat echocardiogram was undertaken after 1-week, which confirmed
      acute endocarditis. The patient was treated with intravenous antibiotics for 6
      weeks with improvement in clinical, radiological and biochemical parameters. 

PMID- 25564587
TI  - Monostotic Paget's disease of the second metacarpal.
AB  - Paget's disease of the bone is a focal chronic disorder proceeding with elevated
      osteoblastic and osteoclastic activity in the affected area. The most common
      sites are pelvis, femur, lower lumbar vertebrae and skull. Monostotic disease is
      reported in 15-30% of all cases. We report a case of monostotic Paget's disease
      of the second metacarpal, which is a rare location even for polyostotic disease. 

PMID- 25564589
TI  - Toxocariasis as a cause of multiple pulmonary nodules in a paediatric patient.

PMID- 25564588
TI  - Biparietal variant of Alzheimer's disease: a rare presentation of a common
      disease.
AB  - Alzheimer's disease (AD) is a clinically heterogeneous disease that may have
      atypical presentations with focal cortical syndromes and relatively preserved
      episodic memory. The posterior variant of AD has two subtypes: occipitotemporal,
      presenting with visuoperceptive impairment, and biparietal, presenting with
      visuospatial dysfunction and apraxia. We report a case of a 51-year-old woman
      with progressive limb apraxia and choreiform movements. Her neuropsychological
      evaluation was compatible with dementia, and revealed ideomotor and ideational
      limb apraxia, severe visuoconstructive ability impairment, dyscalculia and
      posterior aphasia. Workup excluded metabolic, infectious, inflammatory or
      neoplastic causes, and hereditary conditions as Huntington's disease and familial
      AD. Cerebrospinal fluid biomarkers revealed beta-amyloid reduction and tau
      protein increase. Brain imaging showed marked biparietal atrophy and
      hypoperfusion, and widespread cortical beta-amyloid deposition. Biparietal
      variant of AD was diagnosed and acetylcholinesterase inhibitor treatment induced
      clinical stabilisation. AD may present with atypical features and a high clinical
      suspicion is necessary for an early diagnosis. 

PMID- 25564590
TI  - An intriguing case of blurred vision in a young patient.

PMID- 25564591
TI  - Anti-MuSK-positive myasthenia gravis diagnosed during pregnancy: new challenges
      for an old disease?
AB  - Myasthenia gravis is an autoimmune disorder affecting predominantly women in
      their reproductive age. The course of the disease during pregnancy is
      unpredictable, although it is more difficult to manage earlier in the gestation.
      Myasthenia gravis with antibodies against the muscle-specific receptor tyrosine
      kinase (anti-MuSK) has been described as a subtype of disease with more localised
      clinical features and a poorer response to treatment than acetylcholine receptor
      antibody (anti-AChR)-positive patients. Few cases have been reported in pregnant
      women, with deliveries being performed mainly by caesarean section. We report a
      successful case of vaginal delivery and describe our experience providing the
      first review of the management of this subtype of disease during pregnancy. 

PMID- 25564592
TI  - Acute unilateral isolated ptosis.
AB  - A 64-year-old man presented with a 2-day history of acute onset painless left
      ptosis. He had no other symptoms; importantly pupils were equal and reactive and
      eye movements were full. There was no palpable mass or swelling. He was
      systemically well with no headache, other focal neurological signs, or symptoms
      of fatigue. CT imaging showed swelling of the levator palpebrae superioris
      suggestive of myositis. After showing no improvement over 5 days the patient
      started oral prednisolone 30 mg reducing over 12 weeks. The ptosis resolved
      quickly and the patient remains symptom free at 6 months follow-up. Acute ptosis
      may indicate serious pathology. Differential diagnoses include a posterior
      communicating artery aneurysm causing a partial or complete third nerve palsy,
      Horner's syndrome, and myasthenia gravis. A careful history and examination must
      be taken. Orbital myositis typically involves the extraocular muscles causing
      pain and diplopia. Isolated levator myositis is rare. 

PMID- 25564593
TI  - Rare manifestations in a case of Osler-Weber-Rendu disease.
AB  - Osler-Weber-Rendu disease (OWRD) is a rare vascular dysplasia that presents most
      commonly with epistaxis. The most dreaded complication, however, is an
      intracranial haemorrhage. We present a patient with two rare manifestations of
      OWRD, subdural haematoma and portal venous hypertension, both seldom reported in
      the literature. The patient made a full recovery and continues to do well at this
      time. 

PMID- 25564594
TI  - Bilateral total hip arthroplasty in a young man with hereditary multiple
      exostoses.
AB  - We report a rare case of a young man with hereditary multiple exostoses (HME) who
      presented with severe pain in the hips, requiring bilateral total hip
      arthroplasty (THA), along with excision of the exostoses. The reported incidence
      of exostoses around the hip has been reported from 30% in some series to 90% in
      other studies of HME. These patients may remain asymptomatic, but if not, their
      symptoms are usually related to the presence of the exostoses itself and the
      possibility of hip osteoarthrosis is frequently overlooked. This may account for
      a low incidence of THA for this condition. Surgical management often remains
      challenging as such lesions are not commonly encountered in the clinical practice
      and are often very difficult to treat. 

PMID- 25564595
TI  - Macular pseudohaemorrhage secondary to Allen Dot artefact.
AB  - A 34-year-old highly myopic (-11.00 D) woman presented to eye clinic with a 3 day
      history of right eye paracentral blurring. Visual acuities were 6/6 bilaterally.
      Clinical examination was normal. Fundus photography showed the classic appearance
      of a macular haemorrhage. This is a recognised complication of high myopia and
      would have accounted for the patient's symptoms. However, further photography
      showed that the haemorrhage seemed to 'jump' around the fundus and was even
      present in the fellow eye. The apparent haemorrhage was revealed to be an imaging
      artefact. The 'Allen Dot' is a 6 mm black mask incorporated into retinal cameras
      to reduce reflection. Rarely, in highly myopic eyes, optical artefact can result.
      To the best of our knowledge, we are the first in the literature to report
      artefacts from the Allen Dot masquerading as ophthalmic disease. This case re
      iterates the importance of clinical examination, especially in high myopes, given
      the current trend towards virtual clinics. 

PMID- 25564596
TI  - Double jeopardy: two episodes of forearm compartment syndrome in the same
      patient.
AB  - A 55-year-old woman taking warfarin for previous deep venous thrombosis (DVT),
      presented with an acutely swollen and painful forearm after forcefully
      contracting her forearm flexor compartment while using a car hand brake and
      later, an axe. Compartment syndrome was diagnosed and emergency fasciotomy
      performed, with a haematoma discovered between the flexor compartments of flexor
      digitorum superficialis (FDS) and flexor digitorum profundus (FDP). After
      evacuation and resolution of symptoms, the wounds were closed 4 days later.
      Following discharge on the fifth day, symptoms recurred without warning,
      prompting re-exploration and discovery of further haematoma. Symptoms again
      resolved and in due course a skin graft was applied to close the wound without
      tension. 

PMID- 25564598
TI  - An unusual cause of spinal cord ischemia after thoracic endovascular repair.
AB  - A 59-year-old left-handed man presented with chest pain and hypertension and was
      found to have an acute descending aortic dissection on imaging. After thoracic
      endovascular repair of the dissection, he developed left arm weakness and
      ischemia. Despite carotid-subclavian transposition, the patient was found to have
      persistent left triceps weakness as well as bilateral leg paresis. An urgent
      spinal drain was placed that improved his lower extremity deficit but did not
      greatly change his arm symptoms. Magnetic resonance imaging of the spine revealed
      previously undiagnosed severe multilevel spinal stenosis requiring operative
      decompression. To our knowledge, this is the first report of the contribution of
      cervical spinal stenosis to post-thoracic endovascular repair spinal ischemia. 

PMID- 25564599
TI  - JNCI is 75 years old!

PMID- 25564597
TI  - Toxicological effects of carbosulfan in rats: Antioxidant, enzymological,
      biochemical, and hematological responses.
AB  - Carbosulfan is often used in agriculture for pest control on crops and for
      treatment against pyrethroid-resistant mosquitoes. This study investigated the
      impact of carbosulfan on oxidative stress markers, antioxidant defense,
      hematological, biochemical, and enzymological parameters in Sprague Dawley rats.
      Rats were orally administered carbosulfan doses of 1.02 to 10.20 mg/kg body
      weight daily; after 96 h, blood samples were taken, and the liver, kidney, and
      brain were dissected out for study. Results indicate that carbosulfan
      significantly increased the levels of lipid peroxidation and suppressed the
      activity of reduced glutathione, glutathione reductase, catalase, glucose-6
      phosphate dehydrogenase, and adenosine triphosphatase. A mixed trend was observed
      in the activity of superoxide dismutase, while an increase was observed in the
      levels of serum uric acid, urea, aspartate aminotransferase, and alanine
      aminotransferase. Hemoglobin and albumin levels decreased but no significant
      differences were observed in creatinine and bilirubin levels. Future studies
      should include a more detailed analysis of the effects of chronic carbosulfan
      exposure on these biomarkers to further assess the impact of the pesticide on
      mammalian models. 

PMID- 25564600
TI  - More evidence that aspirin lowers cancer risk.

PMID- 25564601
TI  - Electronic cigarettes might not help cancer patients quit smoking.

PMID- 25564602
TI  - Expensive cancer therapies: unintended effects.

PMID- 25564606
TI  - Renewed focus on preventing gastric cancer.

PMID- 25564607
TI  - Membrane targeting of the Spir.formin actin nucleator complex requires a
      sequential handshake of polar interactions.
AB  - Spir and formin (FMN)-type actin nucleators initiate actin polymerization at
      vesicular membranes necessary for long range vesicular transport processes. Here
      we studied in detail the membrane binding properties and protein/protein
      interactions that govern the assembly of the membrane-associated Spir.FMN
      complex. Using biomimetic membrane models we show that binding of the C-terminal
      Spir-2 FYVE-type zinc finger involves both the presence of negatively charged
      lipids and hydrophobic contributions from the turret loop that intrudes the lipid
      bilayer. In solution, we uncovered a yet unknown intramolecular interaction
      between the Spir-2 FYVE-type domain and the N-terminal kinase non-catalytic C
      lobe domain (KIND) that could not be detected in the membrane-bound state.
      Interestingly, we found that the intramolecular Spir-2 FYVE/KIND and the trans
      regulatory Fmn-2-FSI/Spir-2-KIND interactions are competitive. We therefore
      characterized co-expressed Spir-2 and Fmn-2 fluorescent protein fusions in living
      cells by fluorescence cross-correlation spectroscopy. The data corroborate a
      model according to which Spir-2 exists in two different states, a cytosolic
      monomeric conformation and a membrane-bound state in which the KIND domain is
      released and accessible for subsequent Fmn-2 recruitment. This sequence of
      interactions mechanistically couples membrane binding of Spir to the recruitment
      of FMN, a pivotal step for initiating actin nucleation at vesicular membranes. 

PMID- 25564609
TI  - Quality control of a cytoplasmic protein complex: chaperone motors and the
      ubiquitin-proteasome system govern the fate of orphan fatty acid synthase subunit
      Fas2 of yeast.
AB  - For the assembly of protein complexes in the cell, the presence of stoichiometric
      amounts of the respective protein subunits is of utmost importance. A surplus of
      any of the subunits may trigger unspecific and harmful protein interactions and
      has to be avoided. A stoichiometric amount of subunits must finally be reached
      via transcriptional, translational, and/or post-translational regulation.
      Synthesis of saturated 16 and 18 carbon fatty acids is carried out by fatty acid
      synthase: in yeast Saccharomyces cerevisiae, a 2.6-MDa molecular mass assembly
      containing six protomers each of two different subunits, Fas1 (beta) and Fas2
      (alpha). The (alpha)6(beta)6 complex carries six copies of all eight enzymatic
      activities required for fatty acid synthesis. The FAS1 and FAS2 genes in yeast
      are unlinked and map on two different chromosomes. Here we study the fate of the
      alpha-subunit of the complex, Fas2, when its partner, the beta-subunit Fas1, is
      absent. Individual subunits of fatty acid synthase are proteolytically degraded
      when the respective partner is missing. Elimination of Fas2 is achieved by the
      proteasome. Here we show that a ubiquitin transfer machinery is required for Fas2
      elimination. The major ubiquitin ligase targeting the superfluous Fas2 subunit to
      the proteasome is Ubr1. The ubiquitin-conjugating enzymes Ubc2 and Ubc4 assist
      the degradation process. The AAA-ATPase Cdc48 and the Hsp70 chaperone Ssa1 are
      crucially involved in the elimination of Fas2. 

PMID- 25564608
TI  - In situ localization of N and C termini of subunits of the flagellar nexin-dynein
      regulatory complex (N-DRC) using SNAP tag and cryo-electron tomography.
AB  - Cryo-electron tomography (cryo-ET) has reached nanoscale resolution for in situ
      three-dimensional imaging of macromolecular complexes and organelles. Yet its
      current resolution is not sufficient to precisely localize or identify most
      proteins in situ; for example, the location and arrangement of components of the
      nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar
      motility that is conserved from algae to humans, have remained elusive despite
      many cryo-ET studies of cilia and flagella. Here, we developed an in situ
      localization method that combines cryo-ET/subtomogram averaging with the clonable
      SNAP tag, a widely used cell biological probe to visualize fusion proteins by
      fluorescence microscopy. Using this hybrid approach, we precisely determined the
      locations of the N and C termini of DRC3 and the C terminus of DRC4 within the
      three-dimensional structure of the N-DRC in Chlamydomonas flagella. Our data
      demonstrate that fusion of SNAP with target proteins allowed for protein
      localization with high efficiency and fidelity using SNAP-linked gold
      nanoparticles, without disrupting the native assembly, structure, or function of
      the flagella. After cryo-ET and subtomogram averaging, we localized DRC3 to the
      L1 projection of the nexin linker, which interacts directly with a dynein motor,
      whereas DRC4 was observed to stretch along the N-DRC base plate to the nexin
      linker. Application of the technique developed here to the N-DRC revealed new
      insights into the organization and regulatory mechanism of this complex, and
      provides a valuable tool for the structural dissection of macromolecular
      complexes in situ. 

PMID- 25564610
TI  - SUMOylation regulates polo-like kinase 1-interacting checkpoint helicase (PICH)
      during mitosis.
AB  - Mitotic SUMOylation has an essential role in faithful chromosome segregation in
      eukaryotes, although its molecular consequences are not yet fully understood. In
      Xenopus egg extract assays, we showed that poly(ADP-ribose) polymerase 1 (PARP1)
      is modified by SUMO2/3 at mitotic centromeres and that its enzymatic activity
      could be regulated by SUMOylation. To determine the molecular consequence of
      mitotic SUMOylation, we analyzed SUMOylated PARP1-specific binding proteins. We
      identified Polo-like kinase 1-interacting checkpoint helicase (PICH) as an
      interaction partner of SUMOylated PARP1 in Xenopus egg extract. Interestingly,
      PICH also bound to SUMOylated topoisomerase IIalpha (TopoIIalpha), a major
      centromeric small ubiquitin-like modifier (SUMO) substrate. Purified recombinant
      human PICH interacted with SUMOylated substrates, indicating that PICH directly
      interacts with SUMO, and this interaction is conserved among species. Further
      analysis of mitotic chromosomes revealed that PICH localized to the centromere
      independent of mitotic SUMOylation. Additionally, we found that PICH is modified
      by SUMO2/3 on mitotic chromosomes and in vitro. PICH SUMOylation is highly
      dependent on protein inhibitor of activated STAT, PIASy, consistent with other
      mitotic chromosomal SUMO substrates. Finally, the SUMOylation of PICH
      significantly reduced its DNA binding capability, indicating that SUMOylation
      might regulate its DNA-dependent ATPase activity. Collectively, our findings
      suggest a novel SUMO-mediated regulation of the function of PICH at mitotic
      centromeres. 

PMID- 25564611
TI  - Prevalence and gene characteristics of antibodies with cofactor-induced HIV-1
      specificity.
AB  - The healthy immune repertoire contains a fraction of antibodies that bind to
      various biologically relevant cofactors, including heme. Interaction of heme with
      some antibodies results in induction of new antigen binding specificities and
      acquisition of binding polyreactivity. In vivo, extracellular heme is released as
      a result of hemolysis or tissue damage; hence the post-translational acquisition
      of novel antigen specificities might play an important role in the
      diversification of the immunoglobulin repertoire and host defense. Here, we
      demonstrate that seronegative immune repertoires contain antibodies that gain
      reactivity to HIV-1 gp120 upon exposure to heme. Furthermore, a panel of human
      recombinant antibodies was cloned from different B cell subpopulations, and the
      prevalence of antibodies with cofactor-induced specificity for gp120 was
      determined. Our data reveal that upon exposure to heme, ~24% of antibodies
      acquired binding specificity for divergent strains of HIV-1 gp120. Sequence
      analyses reveal that heme-sensitive antibodies do not differ in their repertoire
      of variable region genes and in most of the molecular features of their antigen
      binding sites from antibodies that do not change their antigen binding
      specificity. However, antibodies with cofactor-induced gp120 specificity possess
      significantly lower numbers of somatic mutations in their variable region genes.
      This study contributes to the understanding of the significance of cofactor
      binding antibodies in immunoglobulin repertoires and of the influence that the
      tissue microenvironment might have in shaping adaptive immune responses. 

PMID- 25564612
TI  - Attenuation of the phosphatidylinositol 3-kinase/Akt signaling pathway by
      Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp.
AB  - Porphyromonas gingivalis is a major pathogen of periodontal diseases, including
      periodontitis. We have investigated the effect of P. gingivalis infection on the
      PI3K/Akt (protein kinase B) signaling pathway in gingival epithelial cells. Here,
      we found that live P. gingivalis, but not heat-killed P. gingivalis, reduced Akt
      phosphorylation at both Thr-308 and Ser-473, which implies a decrease in Akt
      activity. Actually, PI3K, which is upstream of Akt, was also inactivated by P.
      gingivalis. Furthermore, glycogen synthase kinase 3alpha/beta, mammalian target
      of rapamycin, and Bad, which are downstream proteins in the PI3K/Akt cascade,
      were also dephosphorylated, a phenomenon consistent with Akt inactivation by P.
      gingivalis. However, these events did not require direct interaction between
      bacteria and host cells and were independent of P. gingivalis invasion into the
      cells. The use of gingipain-specific inhibitors and a gingipain-deficient P.
      gingivalis mutant KDP136 revealed that the gingipains and their protease
      activities were essential for the inactivation of PI3K and Akt. The associations
      between the PI3K regulatory subunit p85alpha and membrane proteins were disrupted
      by wild-type P. gingivalis. Moreover, PDK1 translocation to the plasma membrane
      was reduced by wild-type P. gingivalis, but not KDP136, indicating little
      production of phosphatidylinositol 3,4,5-triphosphate by PI3K. Therefore, it is
      likely that PI3K failed to transmit homeostatic extracellular stimuli to
      intracellular signaling pathways by gingipains. Taken together, our findings
      indicate that P. gingivalis attenuates the PI3K/Akt signaling pathway via the
      proteolytic effects of gingipains, resulting in the dysregulation of PI3K/Akt
      dependent cellular functions and the destruction of epithelial barriers. 

PMID- 25564613
TI  - Insulin-like growth factor 1 (IGF-1) stabilizes nascent blood vessels.
AB  - Here we report that VEGF-A and IGF-1 differ in their ability to stabilize newly
      formed blood vessels and endothelial cell tubes. Although VEGF-A failed to
      support an enduring vascular response, IGF-1 stabilized neovessels generated from
      primary endothelial cells derived from various vascular beds and mouse retinal
      explants. In these experimental systems, destabilization/regression was driven by
      lysophosphatidic acid (LPA). Because previous studies have established that Erk
      antagonizes LPA-mediated regression, we considered whether Erk was an essential
      component of IGF-dependent stabilization. Indeed, IGF-1 lost its ability to
      stabilize neovessels when the Erk pathway was inhibited pharmacologically.
      Furthermore, stabilization was associated with prolonged Erk activity. In the
      presence of IGF-1, Erk activity persisted longer than in the presence of VEGF or
      LPA alone. These studies reveal that VEGF and IGF-1 can have distinct inputs in
      the angiogenic process. In contrast to VEGF, IGF-1 stabilizes neovessels, which
      is dependent on Erk activity and associated with prolonged activation. 

PMID- 25564614
TI  - Structural basis for the formation of acylalkylpyrones from two beta-ketoacyl
      units by the fungal type III polyketide synthase CsyB.
AB  - The acylalkylpyrone synthase CsyB from Aspergillus oryzae catalyzes the one-pot
      formation of the 3-acyl-4-hydroxy-6-alkyl-alpha-pyrone scaffold from acetoacetyl
      CoA, fatty acyl-CoA, and malonyl-CoA. This is the first type III polyketide
      synthase that performs not only the polyketide chain elongation but also the
      condensation of two beta-ketoacyl units. The crystal structures of wild-type CsyB
      and its I375F and I375W mutants were solved at 1.7-, 2.3-, and 2.0-A resolutions,
      respectively. The crystal structures revealed a unique active site architecture
      featuring a hitherto unidentified novel pocket for accommodation of the
      acetoacetyl-CoA starter in addition to the conventional elongation/cyclization
      pocket with the Cys-His-Asn catalytic triad and the long hydrophobic tunnel for
      binding the fatty acyl chain. The structures also indicated the presence of a
      putative nucleophilic water molecule activated by the hydrogen bond networks with
      His-377 and Cys-155 at the active site center. Furthermore, an in vitro enzyme
      reaction confirmed that the (18)O atom of the H2(18)O molecule is enzymatically
      incorporated into the final product. These observations suggested that the enzyme
      reaction is initiated by the loading of acetoacetyl-CoA onto Cys-155, and
      subsequent thioester bond cleavage by the nucleophilic water generates the beta
      keto acid intermediate, which is placed within the novel pocket. The second beta
      ketoacyl unit is then produced by polyketide chain elongation of fatty acyl-CoA
      with one molecule of malonyl-CoA, and the condensation with the beta-keto acid
      generates the final products. Indeed, steric modulation of the novel pocket by
      the structure-based I375F and I375W mutations resulted in altered specificities
      for the chain lengths of the substrates.

PMID- 25564615
TI  - A heterodimer of a VHH (variable domains of camelid heavy chain-only) antibody
      that inhibits anthrax toxin cell binding linked to a VHH antibody that blocks
      oligomer formation is highly protective in an anthrax spore challenge model.
AB  - Anthrax disease is caused by a toxin consisting of protective antigen (PA),
      lethal factor, and edema factor. Antibodies against PA have been shown to be
      protective against the disease. Variable domains of camelid heavy chain-only
      antibodies (VHHs) with affinity for PA were obtained from immunized alpacas and
      screened for anthrax neutralizing activity in macrophage toxicity assays. Two
      classes of neutralizing VHHs were identified recognizing distinct, non
      overlapping epitopes. One class recognizes domain 4 of PA at a well characterized
      neutralizing site through which PA binds to its cellular receptor. A second
      neutralizing VHH (JKH-C7) recognizes a novel epitope. This antibody inhibits
      conversion of the PA oligomer from "pre-pore" to its SDS and heat-resistant
      "pore" conformation while not preventing cleavage of full-length 83-kDa PA (PA83)
      by cell surface proteases to its oligomer-competent 63-kDa form (PA63). The
      antibody prevents endocytosis of the cell surface-generated PA63 subunit but not
      preformed PA63 oligomers formed in solution. JKH-C7 and the receptor-blocking VHH
      class (JIK-B8) were expressed as a heterodimeric VHH-based neutralizing agent
      (VNA2-PA). This VNA displayed improved neutralizing potency in cell assays and
      protected mice from anthrax toxin challenge with much better efficacy than the
      separate component VHHs. The VNA protected virtually all mice when separately
      administered at a 1:1 ratio to toxin and protected mice against Bacillus
      anthracis spore infection. Thus, our studies show the potential of VNAs as
      anthrax therapeutics. Due to their simple and stable nature, VNAs should be
      amenable to genetic delivery or administration via respiratory routes. 

PMID- 25564616
TI  - Rictor/mTORC2 pathway in oocytes regulates folliculogenesis, and its inactivation
      causes premature ovarian failure.
AB  - Molecular basis of ovarian folliculogenesis and etiopathogenesis of premature
      ovarian failure (POF), a common cause of infertility in women, are not fully
      understood. Mechanistic target of rapamycin complex 2 (mTORC2) is emerging as a
      central regulator of cell metabolism, proliferation, and survival. However, its
      role in folliculogenesis and POF has not been reported. Here, we showed that the
      signaling activity of mTORC2 is inhibited in a 4-vinylcyclohexene diepoxide (VCD)
      induced POF mouse model. Notably, mice with oocyte-specific ablation of Rictor, a
      key component of mTORC2, demonstrated POF phenotypes, including massive
      follicular death, excessive loss of functional ovarian follicles, abnormal
      gonadal hormone secretion, and consequently, secondary subfertility in
      conditional knock-out (cKO) mice. Furthermore, reduced levels of Ser-473
      phosphorylated Akt and Ser-253-phosphorylated Foxo3a and elevated pro-apoptotic
      proteins, Bad, Bax, and cleaved poly ADP-ribose polymerase (PARP), were observed
      in cKO mice, replicating the signaling alterations in 4-VCD-treated ovaries.
      These results indicate a critical role of the Rictor/mTORC2/Akt/Foxo3a pro
      survival signaling axis in folliculogenesis. Interestingly, loss of maternal
      Rictor did not cause obvious developmental defects in embryos or placentas from
      cKO mice, suggesting that maternal Rictor is dispensable for preimplantation
      embryonic development. Our results collectively indicate key roles of
      Rictor/mTORC2 in folliculogenesis, follicle survival, and female fertility and
      support the utility of oocyte-specific Rictor knock-out mice as a novel model for
      POF. 

PMID- 25564617
TI  - Unraveling curcumin degradation: autoxidation proceeds through spiroepoxide and
      vinylether intermediates en route to the main bicyclopentadione.
AB  - Curcumin is a dietary anti-inflammatory and chemopreventive agent consisting of
      two methoxyphenol rings connected by a conjugated heptadienedione chain. Curcumin
      is unstable at physiological pH and rapidly degrades in an autoxidation reaction
      to a major bicyclopentadione product in which the 7-carbon chain has undergone
      oxygenation and double cyclization. Early degradation products (but not the final
      bicyclopentadione) mediate topoisomerase poisoning and possibly many other
      activities of curcumin, but it is not known how many and what autoxidation
      products are formed, nor their mechanism of formation. Here, using
      [(14)C2]curcumin as a tracer, seven novel autoxidation products, including two
      reaction intermediates, were isolated and identified using one- and two
      dimensional NMR and mass spectrometry. The unusual spiroepoxide and vinylether
      reaction intermediates are precursors to the final bicyclopentadione product. A
      mechanism for the autoxidation of curcumin is proposed that accounts for the
      addition and exchange of oxygen that have been determined using (18)O2 and
      H2(18)O. Several of the by-products are formed from an endoperoxide intermediate
      via reactions that are well precedented in lipid peroxidation. The electrophilic
      spiroepoxide intermediate formed a stable adduct with N-acetylcysteine,
      suggesting that oxidative transformation is required for biological effects
      mediated by covalent adduction to protein thiols. The spontaneous autoxidation
      distinguishes curcumin among natural polyphenolic compounds of therapeutic
      interest; the formation of chemically diverse reactive and electrophilic products
      provides a novel paradigm for understanding the polypharmacological effects of
      curcumin.

PMID- 25564619
TI  - The Habc domain of the SNARE Vam3 interacts with the HOPS tethering complex to
      facilitate vacuole fusion.
AB  - Membrane fusion at vacuoles requires a consecutive action of the HOPS tethering
      complex, which is recruited by the Rab GTPase Ypt7, and vacuolar SNAREs to drive
      membrane fusion. It is assumed that the Sec1/Munc18-like Vps33 within the HOPS
      complex is largely responsible for SNARE chaperoning. Here, we present direct
      evidence for HOPS binding to SNAREs and the Habc domain of the Vam3 SNARE
      protein, which may explain its function during fusion. We show that HOPS
      interacts strongly with the Vam3 Habc domain, assembled Q-SNAREs, and the R-SNARE
      Ykt6, but not the Q-SNARE Vti1 or the Vam3 SNARE domain. Electron microscopy
      combined with Nanogold labeling reveals that the binding sites for vacuolar
      SNAREs and the Habc domain are located in the large head of the HOPS complex,
      where Vps16 and Vps33 have been identified before. Competition experiments
      suggest that HOPS bound to the Habc domain can still interact with assembled Q
      SNAREs, whereas Q-SNARE binding prevents recognition of the Habc domain. In
      agreement, membranes carrying Vam3DeltaHabc fuse poorly unless an excess of HOPS
      is provided. These data suggest that the Habc domain of Vam3 facilitates the
      assembly of the HOPS/SNARE machinery at fusion sites and thus supports efficient
      membrane fusion. 

PMID- 25564620
TI  - Plant germline formation: common concepts and developmental flexibility in sexual
      and asexual reproduction.
AB  - The life cycle of flowering plants alternates between two heteromorphic
      generations: a diploid sporophytic generation and a haploid gametophytic
      generation. During the development of the plant reproductive lineages - the
      germlines - typically, single sporophytic (somatic) cells in the flower become
      committed to undergo meiosis. The resulting spores subsequently develop into
      highly polarized and differentiated haploid gametophytes that harbour the
      gametes. Recent studies have provided insights into the genetic basis and
      regulatory programs underlying cell specification and the acquisition of
      reproductive fate during both sexual reproduction and asexual (apomictic)
      reproduction. As we review here, these recent advances emphasize the importance
      of transcriptional, translational and post-transcriptional regulation, and the
      role of epigenetic regulatory pathways and hormonal activity. 

PMID- 25564618
TI  - Evidence for restricted reactivity of ADAMDEC1 with protein substrates and
      endogenous inhibitors.
AB  - ADAMDEC1 is a proteolytically active metzincin metalloprotease displaying rare
      active site architecture with a zinc-binding Asp residue (Asp-362). We previously
      demonstrated that substitution of Asp-362 for a His residue, thereby
      reconstituting the canonical metzincin zinc-binding environment with three His
      zinc ligands, increases the proteolytic activity. The protease also has an
      atypically short domain structure with an odd number of Cys residues in the
      metalloprotease domain. Here, we investigated how these rare structural features
      in the ADAMDEC1 metalloprotease domain impact the proteolytic activity, the
      substrate specificity, and the effect of inhibitors. We identified
      carboxymethylated transferrin (Cm-Tf) as a new ADAMDEC1 substrate and determined
      the primary and secondary cleavage sites, which suggests a strong preference for
      Leu in the P1' position. Cys(392), present in humans but only partially conserved
      within sequenced ADAMDEC1 orthologs, was found to be unpaired, and substitution
      of Cys(392) for a Ser increased the reactivity with alpha2-macroglobulin but not
      with casein or Cm-Tf. Substitution of Asp(362) for His resulted in a general
      increase in proteolytic activity and a change in substrate specificity was
      observed with Cm-Tf. ADAMDEC1 was inhibited by the small molecule inhibitor
      batimastat but not by tissue inhibitor of metalloproteases (TIMP)-1, TIMP-2, or
      the N-terminal inhibitory domain of TIMP-3 (N-TIMP-3). However, N-TIMP-3
      displayed profound inhibitory activity against the D362H variants with a
      reconstituted consensus metzincin zinc-binding environment. We hypothesize that
      these unique features of ADAMDEC1 may have evolved to escape from inhibition by
      endogenous metalloprotease inhibitors. 

PMID- 25564623
TI  - Proteasome regulation of the chromodomain protein MRG-1 controls the balance
      between proliferative fate and differentiation in the C. elegans germ line.
AB  - The level of stem cell proliferation must be tightly controlled for proper
      development and tissue homeostasis. Multiple levels of gene regulation are often
      employed to regulate stem cell proliferation to ensure that the amount of
      proliferation is aligned with the needs of the tissue. Here we focus on
      proteasome-mediated protein degradation as a means of regulating the activities
      of proteins involved in controlling the stem cell proliferative fate in the C.
      elegans germ line. We identify five potential E3 ubiquitin ligases, including the
      RFP-1 RING finger protein, as being involved in regulating proliferative fate.
      RFP-1 binds to MRG-1, a homologue of the mammalian chromodomain-containing
      protein MRG15 (MORF4L1), which has been implicated in promoting the proliferation
      of neural precursor cells. We find that C. elegans with reduced proteasome
      activity, or that lack RFP-1 expression, have increased levels of MRG-1 and a
      shift towards increased proliferation in sensitized genetic backgrounds.
      Likewise, reduction of MRG-1 partially suppresses stem cell overproliferation.
      MRG-1 levels are controlled independently of the spatially regulated GLP-1/Notch
      signalling pathway, which is the primary signal controlling the extent of stem
      cell proliferation in the C. elegans germ line. We propose a model in which MRG-1
      levels are controlled, at least in part, by the proteasome, and that the levels
      of MRG-1 set a threshold upon which other spatially regulated factors act in
      order to control the balance between the proliferative fate and differentiation
      in the C. elegans germ line. 

PMID- 25564624
TI  - Microtubule-dependent apical restriction of recycling endosomes sustains adherens
      junctions during morphogenesis of the Drosophila tracheal system.
AB  - Epithelial remodelling is an essential mechanism for organogenesis, during which
      cells change shape and position while maintaining contact with each other.
      Adherens junctions (AJs) mediate stable intercellular cohesion but must be
      actively reorganised to allow morphogenesis. Vesicle trafficking and the
      microtubule (MT) cytoskeleton contribute to regulating AJs but their
      interrelationship remains elusive. We carried out a detailed analysis of the role
      of MTs in cell remodelling during formation of the tracheal system in the
      Drosophila embryo. Induction of MT depolymerisation specifically in tracheal
      cells shows that MTs are essential during a specific time frame of tracheal cell
      elongation while the branch extends. In the absence of MTs, one tracheal cell per
      branch overelongates, ultimately leading to branch break. Three-dimensional
      quantifications revealed that MTs are crucial to sustain E-Cadherin (Shotgun) and
      Par-3 (Bazooka) levels at AJs. Maintaining E-Cadherin/Par-3 levels at the apical
      domain requires de novo synthesis rather than internalisation and recycling from
      and to the apical plasma membrane. However, apical targeting of E-Cadherin and
      Par-3 requires functional recycling endosomes, suggesting an intermediate role
      for this compartment in targeting de novo synthesized E-Cadherin to the plasma
      membrane. We demonstrate that apical enrichment of recycling endosomes is
      dependent on the MT motor Dynein and essential for the function of this vesicular
      compartment. In addition, we establish that E-Cadherin dynamics and MT
      requirement differ in remodelling tracheal cells versus planar epithelial cells.
      Altogether, our results uncover an MT-Dynein-dependent apical restriction of
      recycling endosomes that controls adhesion by sustaining Par-3 and E-Cadherin
      levels at AJs during morphogenesis. 

PMID- 25564622
TI  - Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors.
AB  - Basal cells are multipotent airway progenitors that generate distinct epithelial
      cell phenotypes crucial for homeostasis and repair of the conducting airways.
      Little is known about how these progenitor cells expand and transition to
      differentiation to form the pseudostratified airway epithelium in the developing
      and adult lung. Here, we show by genetic and pharmacological approaches that
      endogenous activation of Notch3 signaling selectively controls the pool of
      undifferentiated progenitors of upper airways available for differentiation. This
      mechanism depends on the availability of Jag1 and Jag2, and is key to generating
      a population of parabasal cells that later activates Notch1 and Notch2 for
      secretory-multiciliated cell fate selection. Disruption of this mechanism
      resulted in aberrant expansion of basal cells and altered pseudostratification.
      Analysis of human lungs showing similar abnormalities and decreased NOTCH3
      expression in subjects with chronic obstructive pulmonary disease suggests an
      involvement of NOTCH3-dependent events in the pathogenesis of this condition. 

PMID- 25564621
TI  - Establishing neural crest identity: a gene regulatory recipe.
AB  - The neural crest is a stem/progenitor cell population that contributes to a wide
      variety of derivatives, including sensory and autonomic ganglia, cartilage and
      bone of the face and pigment cells of the skin. Unique to vertebrate embryos, it
      has served as an excellent model system for the study of cell behavior and
      identity owing to its multipotency, motility and ability to form a broad array of
      cell types. Neural crest development is thought to be controlled by a suite of
      transcriptional and epigenetic inputs arranged hierarchically in a gene
      regulatory network. Here, we examine neural crest development from a gene
      regulatory perspective and discuss how the underlying genetic circuitry results
      in the features that define this unique cell population. 

PMID- 25564627
TI  - Inner workings: fossil farm.

PMID- 25564625
TI  - Zbtb20 regulates the terminal differentiation of hypertrophic chondrocytes via
      repression of Sox9.
AB  - The terminal differentiation of hypertrophic chondrocytes is a tightly regulated
      process that plays a pivotal role in endochondral ossification. As a negative
      regulator, Sox9 is essentially downregulated in terminally differentiated
      hypertrophic chondrocytes. However, the underlying mechanism of Sox9 silencing is
      undefined. Here we show that the zinc finger protein Zbtb20 regulates the
      terminal differentiation of hypertrophic chondrocytes by repressing Sox9. In the
      developing skeleton of the mouse, Zbtb20 protein is highly expressed by
      hypertrophic chondrocytes from late embryonic stages. To determine its
      physiological role in endochondral ossification, we have generated chondrocyte
      specific Zbtb20 knockout mice and demonstrate that disruption of Zbtb20 in
      chondrocytes results in delayed endochondral ossification and postnatal growth
      retardation. Zbtb20 deficiency caused a delay in cartilage vascularization and an
      expansion of the hypertrophic zone owing to reduced expression of Vegfa in the
      hypertrophic zone. Interestingly, Sox9, a direct suppressor of Vegfa expression,
      was ectopically upregulated at both mRNA and protein levels in the late Zbtb20
      deficient hypertrophic zone. Furthermore, knockdown of Sox9 greatly increased
      Vegfa expression in Zbtb20-deficient hypertrophic chondrocytes. Our findings
      point to Zbtb20 as a crucial regulator governing the terminal differentiation of
      hypertrophic chondrocytes at least partially through repression of Sox9. 

PMID- 25564628
TI  - Core concept: Quantum turbulence.

PMID- 25564630
TI  - Achalasia: a risk factor that must not be forgotten for esophageal squamous cell
      carcinoma.
AB  - Alcohol and tobacco abuse are the main risk factors for esophageal squamous cell
      carcinoma (ESCC), but other conditions that induce chronic irritation of the
      esophageal mucosa have also been attributed to it. For example, long-standing
      achalasia increases 16 times the risk of developing ESCC. We report the case of a
      patient with long-standing achalasia who developed ESCC. Although this
      complication is infrequent, it should be remembered by clinicians who treat
      patients with achalasia to detect early stages cancer. 

PMID- 25564631
TI  - Three testicles in one hemiscrotum: an unusual presentation of polyorchidism.
AB  - Polyorchidism, or more than one testicle in a hemiscrotum, is a relatively rare
      phenomenon. It is often associated with several other conditions, including
      inguinal hernia, testicular maldescent, testicular torsion, hydrocele or
      hypospadias. In this report, we describe a patient who presented with three
      testicles in one hemiscrotum, which is a highly unusual presentation for an
      already uncommon condition. We also review the relevant literature as it relates
      to the need for surveillance due to the increased risk for malignancy. 

PMID- 25564632
TI  - Unilateral persistent hyperplastic primary vitreous: intensive management
      approach with excellent outcome beyond visual maturation.
AB  - Persistent hyperplastic primary vitreous (PHPV) is an ocular developmental
      disorder resulting from incomplete apoptosis of the embryonic hyaloid
      vasculature. Unilateral PHPV is traditionally associated with a poor prognosis
      because of the challenges associated with managing progressive anisometropic
      amblyopia. We report a child with unilateral PHPV who underwent cataract
      extraction, primary posterior capsulotomy with anterior vitrectomy and
      intraocular lens implantation followed by combined trabeculectomy/trabeculotomy
      within the first 8 weeks of life. Intensive optometric and orthoptic input was
      required for many years to manage the increasing anisometropic amblyopia with
      final visual acuity of 20/40 unaided in the affected eye and without evidence of
      glaucomatous optic neuropathy. This case illustrates the excellent visual outcome
      possible in a child with complex, unilateral PHPV using an intensive management
      approach comprising: early surgical intervention for congenital cataract and
      secondary glaucoma, meticulous monitoring of refraction, visual acuity and
      intraocular pressure and motivated parents who engaged in the management. 

PMID- 25564633
TI  - Late onset of cryptococcal cervical lymphadenitis following immune reconstitution
      inflammatory syndrome in a patient with AIDS.
AB  - A 32-year-old woman was diagnosed HIV positive with disseminated cryptococcal
      infection in May 2006. Her initial CD4 was 7 cells/uL and she had a right
      supraclavicular nodal mass, which was biopsied and shown to be consistent with
      cryptococcal lymphadenitis. She was treated for disseminated cryptococcal
      infection and was started on antiretroviral medications subsequently. Two years
      later, she developed a left supraclavicular mass. Her CD4 count was 320 cells/uL
      and HIV RNA level was undetectable. Investigations and biopsy results were
      consistent with a late presentation of cryptococcal immune reconstitution
      inflammatory syndrome (IRIS). She was treated with oral corticosteroids and her
      symptoms resolved completely. IRIS is a recognised complication of HIV treatment
      and occurs in a significant percentage of patients within the first 3 months of
      starting antiretroviral therapy. This case report illustrates the importance of
      recognising late presentations of IRIS. It is vital to differentiate true
      cryptococcal lymphadenitis from IRIS-induced cryptococcal lymphadenitis. 

PMID- 25564634
TI  - Intrauterine tamponade balloon use in the treatment of uterine inversion.
AB  - Uterine inversion is a rare but life-threatening obstetrical emergency that
      occurs when the fundus of the uterus prolapses through the cervix, hence turning
      the uterus inside out. In this case report, we present our experience using an
      intrauterine tamponade balloon for management of uterine inversion, and a review
      of the literature. The utility of an intrauterine tamponade balloon in cases of
      uterine inversion, especially when maternal medical conditions preclude the use
      of uterotonics, or reinversion is observed should be kept in mind. 

PMID- 25564635
TI  - Sister Mary Joseph nodule.

PMID- 25564636
TI  - Tuberculosis of the triceps muscle.
AB  - A tubercular swelling of the triceps muscle in a 25-year-old immunocompetent man
      is described in this report. He presented with hard, fixed swelling at the lower
      end of the triceps muscle. Confirmatory diagnosis was established by fine-needle
      aspiration cytology (FNAC) of the swelling with subsequent PCR for Mycobacterium
      tuberculosis of the FNAC specimen. The patient was completely cured with
      antitubercular therapy. 

PMID- 25564637
TI  - Rectal perforation after neoadjuvant chemoradiotherapy for low-lying rectal
      cancer.

PMID- 25564638
TI  - Resolution of NASH with weight loss documented by hepatic MRI.
AB  - A 57-year-old Asian woman with type 2 diabetes mellitus, hypertension, obesity,
      dyslipidaemia and history of breast cancer, was referred to the cardiovascular
      health and lipid centre for evaluation and management of dyslipidaemia and NASH
      (Non-alcoholic steatohepatitis) in 2010. She originally had a detailed work up at
      the liver clinic for elevated liver enzymes, with no associated symptoms. Initial
      hepatic MRI on 22 January 2007 showed diffuse fatty infiltration quantitated at
      15%. We counselled her on lifestyle modifications, including dietary measures and
      exercise, geared toward weight loss. Over the next 2 years, she lost 24.5 lbs;
      repeat hepatic MRI on 22 December 2011 showed 6% hepatic fat, which is within the
      normal range. This case demonstrates the efficacy of significant weight loss in
      the improvement and resolution of NASH. We believe that this is the first case
      report documenting this through liver MRI. 

PMID- 25564639
TI  - Hydrocephalus due to extreme dilation of Virchow-Robin spaces.
AB  - Virchow-Robin spaces (VRS) are extensions of the subarachnoid space surrounding
      perforating blood vessels entering the brain parenchyma. VRS are fluid filled,
      but almost virtual and only visible on MRI of the brain when dilated. Such
      dilations are commonly asymptomatic. In rare cases, extreme dilations can be
      observed; the clinical repercussions of which remain unclear. We report the case
      of a patient presenting symptoms of normal pressure hydrocephalus due to extreme
      VRS mesencephalon dilations. 

PMID- 25564640
TI  - An unusual presentation of ulcerative colitis.
AB  - Ulcerative colitis (UC) may have diverse extraintestinal manifestations.
      Nutritional deficiencies, medications or immune-mediated epiphenomena are
      considered to be pathogenic mechanisms involved. We describe a case of a 56-year
      old woman who presented with rapidly progressive tingling paraesthesias in both
      lower limbs followed by sensory ataxia, ascending spastic quadriparesis, urgency
      and urge incontinence of 3 months duration. She had an episode of bloody
      diarrhoea 1 month later for which a colonoscopy was carried out with colonic
      biopsy features revealing a diagnosis of UC. In view of lack of alternative
      aetiology, the posterolateral column disease in our patient was attributed to an
      extraintestinal manifestation of UC. She improved dramatically with a course of
      intravenous steroids followed by tapering dose of oral steroids and oral
      mesalamine for her UC. Although rare, UC should be considered in the differential
      diagnosis of posterolateral column disease of the spinal cord in the appropriate
      clinical scenario. 

PMID- 25564642
TI  - Salzmann nodular degeneration associated with epithelial ingrowth after LASIK
      treated with superficial keratectomy.
AB  - A 41-year-old woman who underwent uncomplicated LASIK and two subsequent flap
      lifts for epithelial ingrowth of the right eye became progressively symptomatic
      with blurred vision, photophobia and foreign body sensation over the ensuing 5
      years. Clinical examination of the right eye demonstrated extensive epithelial
      ingrowth around the flap periphery with overlying Salzmann nodules in the same
      distribution. Similar findings were not present in the left eye. Anterior segment
      optical coherence tomography demonstrated subclinical flap elevation in the areas
      of epithelial ingrowth, which may have predisposed to nodule development due to a
      dellen effect. The patient underwent superficial keratectomy with significant
      improvement of her symptoms.

PMID- 25564641
TI  - Refractory hypoglycaemia in patient with gastric outlet obstruction.
AB  - A 68-year-old male with a longstanding history of severe gastric outlet
      obstruction secondary to peptic stricture was found unconscious at home with
      profound hypoglycaemia. He denied history of fasting, diabetes mellitus or use of
      hypoglycaemic agents. Systemic examination and metabolic profile were
      unremarkable. Hypoglycaemic episodes persisted during hospitalisation, requiring
      continuous intravenous dextrose and eventually diazoxide. Further investigative
      work up, including 72 h fasting study, revealed a hyperinsulinemic state. MRI and
      endoscopic ultrasound were unremarkable but mesenteric angiography with hepatic
      venous sampling revealed a subtle area of hypervascularity in the head of
      pancreas. An exploratory laparotomy was then performed and resulted in resection
      of a nodular lesion in the head of pancreas with retrocolic gastrojejunostomy for
      repair of pyloric stenosis. Histopathology of pancreatic nodule confirmed
      nesidioblastosis. Postoperatively the patient was weaned of parenteral dextrose
      and did not have any further episodes of hypoglycaemia. 

PMID- 25564643
TI  - A straightforward stroke? Maybe not: atypical presentation of type A aortic
      dissection.

PMID- 25564644
TI  - Fusion of permanent maxillary right central incisor and mesiodens in an 8-year
      old child.

PMID- 25564645
TI  - Renal replacement lipomatosis of the right kidney.

PMID- 25564646
TI  - Asymptomatic internal hernia through a defect of broad ligament: a surprising
      finding in a laparoscopic surgery to recover a lost levonorgestrel-releasing
      intrauterine system.

PMID- 25564647
TI  - The differential activation of intracellular signaling pathways confers the
      permissiveness of embryonic stem cell derivation from different mouse strains.
AB  - The requirement of leukemia inhibitory factor (LIF) for the establishment and
      maintenance of mouse embryonic stem cells (ESCs) depends on the genetic
      background of the ESC origin. To reveal the molecular basis of the strain
      dependent function of LIF, we compared the activation of the intracellular
      signaling pathways downstream of LIF in ESCs with different genetic backgrounds.
      We found that the JAK-Stat3 pathway was dominantly activated in ESCs derived from
      'permissive' mouse strains (129Sv and C57BL6), whereas the MAP kinase pathway was
      hyperactivated in ESCs from 'non-permissive' strains (NOD, CBA and FVB).
      Artificial activation of Stat3 supported stable self-renewal of ESCs from non
      permissive strains. These data suggest that the difference in the balance between
      the two intracellular signaling pathways underlies the differential response to
      LIF. 

PMID- 25564648
TI  - beta-Catenin-dependent transcription is central to Bmp-mediated formation of
      venous vessels.
AB  - beta-catenin regulates the transcription of genes involved in diverse biological
      processes, including embryogenesis, tissue homeostasis and regeneration.
      Endothelial cell (EC)-specific gene-targeting analyses in mice have revealed that
      beta-catenin is required for vascular development. However, the precise function
      of beta-catenin-mediated gene regulation in vascular development is not well
      understood, since beta-catenin regulates not only gene expression but also the
      formation of cell-cell junctions. To address this question, we have developed a
      novel transgenic zebrafish line that allows the visualization of beta-catenin
      transcriptional activity specifically in ECs and discovered that beta-catenin
      dependent transcription is central to the bone morphogenetic protein (Bmp)
      mediated formation of venous vessels. During caudal vein (CV) formation, Bmp
      induces the expression of aggf1, a putative causative gene for Klippel-Trenaunay
      syndrome, which is characterized by venous malformation and hypertrophy of bones
      and soft tissues. Subsequently, Aggf1 potentiates beta-catenin transcriptional
      activity by acting as a transcriptional co-factor, suggesting that Bmp evokes
      beta-catenin-mediated gene expression through Aggf1 expression. Bmp-mediated
      activation of beta-catenin induces the expression of Nr2f2 (also known as Coup
      TFII), a member of the nuclear receptor superfamily, to promote the
      differentiation of venous ECs, thereby contributing to CV formation. Furthermore,
      beta-catenin stimulated by Bmp promotes the survival of venous ECs, but not that
      of arterial ECs. Collectively, these results indicate that Bmp-induced activation
      of beta-catenin through Aggf1 regulates CV development by promoting the Nr2f2
      dependent differentiation of venous ECs and their survival. This study
      demonstrates, for the first time, a crucial role of beta-catenin-mediated gene
      expression in the development of venous vessels. 

PMID- 25564649
TI  - Regulation of ECM degradation and axon guidance by growth cone invadosomes.
AB  - Invadopodia and podosomes, collectively referred to as invadosomes, are F-actin
      rich basal protrusions of cells that provide sites of attachment to and
      degradation of the extracellular matrix. Invadosomes promote the invasion of
      cells, ranging from metastatic cancer cells to immune cells, into tissue. Here,
      we show that neuronal growth cones form protrusions that share molecular,
      structural and functional characteristics of invadosomes. Growth cones from all
      neuron types and species examined, including a variety of human neurons, form
      invadosomes both in vitro and in vivo. Growth cone invadosomes contain dynamic F
      actin and several actin regulatory proteins, as well as Tks5 and matrix
      metalloproteinases, which locally degrade the matrix. When viewed using three
      dimensional super-resolution microscopy, F-actin foci often extended together
      with microtubules within orthogonal protrusions emanating from the growth cone
      central domain. Finally, inhibiting the function of Tks5 both reduced matrix
      degradation in vitro and disrupted motoneuron axons from exiting the spinal cord
      and extending into the periphery. Taken together, our results suggest that growth
      cones use invadosomes to target protease activity during axon guidance through
      tissues. 

PMID- 25564650
TI  - DNA hypomethylation induces a DNA replication-associated cell cycle arrest to
      block hepatic outgrowth in uhrf1 mutant zebrafish embryos.
AB  - UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1
      to hemimethylated DNA during replication and is essential for maintaining DNA
      methylation. uhrf1 mutant zebrafish have global DNA hypomethylation and display
      embryonic defects, including a small liver, and they die as larvae. We make the
      surprising finding that, despite their reduced organ size, uhrf1 mutants express
      high levels of genes controlling S-phase and have many more cells undergoing DNA
      replication, as measured by BrdU incorporation. In contrast to wild-type
      hepatocytes, which are continually dividing during hepatic outgrowth and thus
      dilute the BrdU label, uhrf1 mutant hepatocytes retain BrdU throughout outgrowth,
      reflecting cell cycle arrest. Pulse-chase-pulse experiments with BrdU and EdU,
      and DNA content analysis indicate that uhrf1 mutant cells undergo DNA re
      replication and that apoptosis is the fate of many of the re-replicating and
      arrested hepatocytes. Importantly, the DNA re-replication phenotype and hepatic
      outgrowth failure are preceded by global loss of DNA methylation. Moreover, uhrf1
      mutants are phenocopied by mutation of dnmt1, and Dnmt1 knockdown in uhrf1
      mutants enhances their small liver phenotype. Together, these data indicate that
      unscheduled DNA replication and failed cell cycle progression leading to
      apoptosis are the mechanisms by which DNA hypomethylation prevents organ
      expansion in uhrf1 mutants. We propose that cell cycle arrest leading to
      apoptosis is a strategy that restricts propagation of epigenetically damaged
      cells during embryogenesis. 

PMID- 25564651
TI  - Surrounding tissues canalize motile cardiopharyngeal progenitors towards
      collective polarity and directed migration.
AB  - Collectively migrating cells maintain group polarity and interpret external cues
      to reach their destination. The cardiogenic progenitors (also known as trunk
      ventral cells, TVCs) of the ascidian Ciona intestinalis provide a simple chordate
      model with which to study collective migration. Bilateral pairs of associated
      TVCs undergo a stereotyped polarized migration away from the tail towards the
      ventral trunk, arguably constituting the simplest possible example of directed
      collective migration. To identify tissues contributing to TVC polarity and
      migration, we quantified the contact between TVCs and surrounding tissues, and
      blocked the secretory pathway in a tissue-specific manner. Even though TVCs
      normally migrate as an invariably determined leader-trailer polarized pair of
      adherent cells, they are capable of migrating individually, albeit a shorter
      distance and with altered morphology. The mesenchyme contacts newborn TVCs and
      contributes to robust specification of the trailer but appears to have only minor
      effects on directed migration. The notochord does not contact the TVCs but
      contributes to the onset of migration. The trunk endoderm first contacts the
      leader TVC, then 'encases' both migrating cells and provides the inputs
      maintaining leader-trailer polarity. Migrating TVCs adhere to the epidermis and
      need this contact for their cohesion. These phenomenological studies reveal that
      inherently motile cardiopharyngeal progenitors are channeled into stereotyped
      behaviors by interactions with surrounding tissues. 

PMID- 25564652
TI  - Tetraspanin CD9 and ectonucleotidase CD73 identify an osteochondroprogenitor
      population with elevated osteogenic properties.
AB  - Cell-based bone regeneration strategies offer promise for traumatic bone
      injuries, congenital defects, non-union fractures and other skeletal pathologies.
      Postnatal bone remodeling and fracture healing provide evidence that an
      osteochondroprogenitor cell is present in adult life that can differentiate to
      remodel or repair the fractured bone. However, cell-based skeletal repair in the
      clinic is still in its infancy, mostly due to poor characterization of progenitor
      cells and lack of knowledge about their in vivo behavior. Here, we took a
      combined approach of high-throughput screening, flow-based cell sorting and in
      vivo transplantation to isolate markers that identify osteochondroprogenitor
      cells. We show that the presence of tetraspanin CD9 enriches for
      osteochondroprogenitors within CD105(+) mesenchymal cells and that these cells
      readily form bone upon transplantation. In addition, we have used Thy1.2 and the
      ectonucleotidase CD73 to identify subsets within the CD9(+) population that lead
      to endochondral or intramembranous-like bone formation. Utilization of this
      unique cell surface phenotype to enrich for osteochondroprogenitor cells will
      allow for further characterization of the molecular mechanisms that regulate
      their osteogenic properties. 

PMID- 25564654
TI  - Mediator Med23 deficiency enhances neural differentiation of murine embryonic
      stem cells through modulating BMP signaling.
AB  - Unraveling the mechanisms underlying early neural differentiation of embryonic
      stem cells (ESCs) is crucial to developing cell-based therapies of
      neurodegenerative diseases. Neural fate acquisition is proposed to be controlled
      by a 'default' mechanism, for which the molecular regulation is not well
      understood. In this study, we investigated the functional roles of Mediator Med23
      in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found
      that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23
      depletion rendered the cells prone to neural differentiation in different
      differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15,
      did not alter the neural differentiation of ESCs. Med15 knockdown selectively
      inhibited endoderm differentiation, suggesting the specificity of cell fate
      control by distinctive Mediator subunits. Gene profiling revealed that Med23
      depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4
      expression by controlling the activity of ETS1, which is involved in Bmp4
      promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish
      embryos also enhanced neural development at early embryogenesis, which could be
      reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an
      intrinsic, restrictive role of MED23 in early neural development, thus providing
      new molecular insights for neural fate determination. 

PMID- 25564653
TI  - ERBB3-mediated regulation of Bergmann glia proliferation in cerebellar
      lamination.
AB  - Cortical lamination is crucial for the assembly of cerebellar circuitry. In this
      process, granule neurons (GNs) migrate along Bergmann glia (BG), which are
      specialized astroglial cells, from the external granule layer to the internal
      granule layer. However, the molecular mechanisms underlying BG development are
      not well understood. Here, we show that GFAP::Cre;Erbb3(F/F) mice, which lack
      Erbb3 in both radial glia and neurons, exhibit impairments in balance and motor
      coordination. Cerebellar lamination is aberrant, with misplaced Purkinje neurons
      and GN clusters. These phenotypes were not observed in
      Math1::CreER(T2);Erbb3(F/F) mice, where the Erbb3 gene was deleted in GNs,
      suggesting involvement of non-neuronal Erbb3 in cerebellar lamination.
      Mechanistic studies indicate that ERBB3 is crucial for the proliferation of BG,
      which are required for GN migration. These observations identify a crucial role
      for ERBB3 in cerebellar lamination and reveal a novel mechanism that regulates BG
      development. 

PMID- 25564655
TI  - AIL and HDG proteins act antagonistically to control cell proliferation.
AB  - Aintegumenta-like (AIL) transcription factors are key regulators of cell
      proliferation and meristem identity. Although AIL functions have been well
      described, the direct signalling components of this pathway are largely unknown.
      We show that baby boom (BBM) and other AIL proteins physically interact with
      multiple members of the L1-expressed homeodomain glabrous (HDG) transcription
      factor family, including HDG1, HDG11 and HDG12. Overexpression of HDG1, HDG11 and
      HDG12 restricts growth due to root and shoot meristem arrest, which is associated
      with reduced expression of genes involved in meristem development and cell
      proliferation pathways, whereas downregulation of multiple HDG genes promotes
      cell overproliferation. These results suggest a role for HDG proteins in
      promoting cell differentiation. We also reveal a transcriptional network in which
      BBM and HDG1 regulate several common target genes, and where BBM/AIL and HDG
      regulate the expression of each other. Taken together, these results suggest
      opposite roles for AIL and HDG proteins, with AILs promoting cell proliferation
      and HDGs stimulating cell differentiation, and that these functions are mediated
      at both the protein-protein interaction and transcriptional level.

PMID- 25564656
TI  - Meta-analysis of expression of hepatic organic anion-transporting polypeptide
      (OATP) transporters in cellular systems relative to human liver tissue.
AB  - Organic anion-transporting polypeptide (OATP)1B1, OATP1B3, and OATP2B1
      transporters play an important role in hepatic drug disposition. Recently, an
      increasing number of studies have reported proteomic expression data for OATP
      transporters. However, systematic analysis and understanding of the actual
      differences in OATP expression between liver tissue and commonly used cellular
      systems is lacking. In the current study, meta-analysis was performed to assess
      the protein expression of OATP transporters reported in hepatocytes relative to
      liver tissue and to identify any potential correlations in transporter expression
      levels in the same individual. OATP1B1 was identified as the most abundant uptake
      transporter at 5.9 +/- 8.3, 5.8 +/- 3.3, and 4.2 +/- 1.7 fmol/MUg protein in
      liver tissue, sandwich-cultured human hepatocytes (SCHH), and cryopreserved
      suspended hepatocytes, respectively. The rank order in average expression in
      liver tissue and cellular systems was OATP1B1 > OATP1B3 ~ OATP2B1. Abundance
      levels of the OATP transporters investigated were not significantly different
      between liver and cellular systems, with the exception of OATP2B1 expression in
      SCHH relative to liver tissue. Analysis of OATP1B1, OATP1B3, and OATP2B1 liver
      expression data in the same individuals (n = 86) identified weak (OATP1B1
      OATP2B1) to moderately (OATP1B3-OATP2B1) significant correlations. A significant
      weak correlation was noted between OATP1B1 abundance and age of human donors,
      whereas expression of the OATPs investigated was independent of sex. Implications
      of the current analysis on the in vitro-in vivo extrapolation of transporter
      mediated drug disposition using physiologically based pharmacokinetic models are
      discussed. 

PMID- 25564657
TI  - Response to Ekstrom et al regarding low-dose opioids in advanced chronic
      obstructive pulmonary disease.

PMID- 25564658
TI  - Low-dose opioids should be considered for symptom relief also in advanced chronic
      obstructive pulmonary disease (COPD).

PMID- 25564659
TI  - Transmitting risk effectively in studies is feasible, but insufficient for shared
      decision-making.

PMID- 25564660
TI  - Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids.
AB  - A central paradox in type 2 diabetes is the apparent selective nature of hepatic
      insulin resistance--wherein insulin fails to suppress hepatic glucose production
      yet continues to stimulate lipogenesis, resulting in hyperglycemia,
      hyperlipidemia, and hepatic steatosis. Although efforts to explain this have
      focused on finding a branch point in insulin signaling where hepatic glucose and
      lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis
      could be driven by substrate, independent of changes in hepatic insulin
      signaling. We tested this hypothesis in rats by infusing [U-(13)C] palmitate to
      measure rates of fatty acid esterification into hepatic triglyceride while
      varying plasma fatty acid and insulin concentrations independently. These
      experiments were performed in normal rats, high fat-fed insulin-resistant rats,
      and insulin receptor 2'-O-methoxyethyl chimeric antisense oligonucleotide-treated
      rats. Rates of fatty acid esterification into hepatic triglyceride were found to
      be dependent on plasma fatty acid infusion rates, independent of changes in
      plasma insulin concentrations and independent of hepatocellular insulin
      signaling. Taken together, these results obviate a paradox of selective insulin
      resistance, because the major source of hepatic lipid synthesis, esterification
      of preformed fatty acids, is primarily dependent on substrate delivery and
      largely independent of hepatic insulin action.

PMID- 25564661
TI  - Inflammation-sensitive super enhancers form domains of coordinately regulated
      enhancer RNAs.
AB  - Enhancers are critical genomic elements that define cellular and functional
      identity through the spatial and temporal regulation of gene expression. Recent
      studies suggest that key genes regulating cell type-specific functions reside in
      enhancer-dense genomic regions (i.e., super enhancers, stretch enhancers). Here
      we report that enhancer RNAs (eRNAs) identified by global nuclear run-on
      sequencing are extensively transcribed within super enhancers and are dynamically
      regulated in response to cellular signaling. Using Toll-like receptor 4 (TLR4)
      signaling in macrophages as a model system, we find that transcription of super
      enhancer-associated eRNAs is dynamically induced at most of the key genes driving
      innate immunity and inflammation. Unexpectedly, genes repressed by TLR4 signaling
      are also associated with super enhancer domains and accompanied by massive
      repression of eRNA transcription. Furthermore, we find each super enhancer acts
      as a single regulatory unit within which eRNA and genic transcripts are
      coordinately regulated. The key regulatory activity of these domains is further
      supported by the finding that super enhancer-associated transcription factor
      binding is twice as likely to be conserved between human and mouse than typical
      enhancer sites. Our study suggests that transcriptional activities at super
      enhancers are critical components to understand the dynamic gene regulatory
      network. 

PMID- 25564662
TI  - Genetic dissection of pheromone processing reveals main olfactory system-mediated
      social behaviors in mice.
AB  - Most mammals have two major olfactory subsystems: the main olfactory system (MOS)
      and vomeronasal system (VNS). It is now widely accepted that the range of
      pheromones that control social behaviors are processed by both the VNS and the
      MOS. However, the functional contributions of each subsystem in social behavior
      remain unclear. To genetically dissociate the MOS and VNS functions, we
      established two conditional knockout mouse lines that led to either loss-of
      function in the entire MOS or in the dorsal MOS. Mice with whole-MOS loss-of
      function displayed severe defects in active sniffing and poor survival through
      the neonatal period. In contrast, when loss-of-function was confined to the
      dorsal MOB, sniffing behavior, pheromone recognition, and VNS activity were
      maintained. However, defects in a wide spectrum of social behaviors were
      observed: attraction to female urine and the accompanying ultrasonic
      vocalizations, chemoinvestigatory preference, aggression, maternal behaviors, and
      risk-assessment behaviors in response to an alarm pheromone. Functional
      dissociation of pheromone detection and pheromonal induction of behaviors showed
      the anterior olfactory nucleus (AON)-regulated social behaviors downstream from
      the MOS. Lesion analysis and neural activation mapping showed pheromonal
      activation in multiple amygdaloid and hypothalamic nuclei, important regions for
      the expression of social behavior, was dependent on MOS and AON functions.
      Identification of the MOS-AON-mediated pheromone pathway may provide insights
      into pheromone signaling in animals that do not possess a functional VNS,
      including humans. 

PMID- 25564663
TI  - Modulation of folding energy landscape by charge-charge interactions: linking
      experiments with computational modeling.
AB  - The kinetics of folding-unfolding of a structurally diverse set of four proteins
      optimized for thermodynamic stability by rational redesign of surface charge
      charge interactions is characterized experimentally. The folding rates are faster
      for designed variants compared with their wild-type proteins, whereas the
      unfolding rates are largely unaffected. A simple structure-based computational
      model, which incorporates the Debye-Huckel formalism for the electrostatics, was
      used and found to qualitatively recapitulate the experimental results. Analysis
      of the energy landscapes of the designed versus wild-type proteins indicates the
      differences in refolding rates may be correlated with the degree of frustration
      of their respective energy landscapes. Our simulations indicate that naturally
      occurring wild-type proteins have frustrated folding landscapes due to the
      surface electrostatics. Optimization of the surface electrostatics seems to
      remove some of that frustration, leading to enhanced formation of native-like
      contacts in the transition-state ensembles (TSE) and providing a less frustrated
      energy landscape between the unfolded and TS ensembles. Macroscopically, this
      results in faster folding rates. Furthermore, analyses of pairwise distances and
      radii of gyration suggest that the less frustrated energy landscapes for
      optimized variants are a result of more compact unfolded and TS ensembles. These
      findings from our modeling demonstrates that this simple model may be used to:
      (i) gain a detailed understanding of charge-charge interactions and their effects
      on modulating the energy landscape of protein folding and (ii) qualitatively
      predict the kinetic behavior of protein surface electrostatic interactions. 

PMID- 25564664
TI  - Antimalarial 4(1H)-pyridones bind to the Qi site of cytochrome bc1.
AB  - Cytochrome bc1 is a proven drug target in the prevention and treatment of
      malaria. The rise in drug-resistant strains of Plasmodium falciparum, the
      organism responsible for malaria, has generated a global effort in designing new
      classes of drugs. Much of the design/redesign work on overcoming this resistance
      has been focused on compounds that are presumed to bind the Q(o) site (one of two
      potential binding sites within cytochrome bc1 using the known crystal structure
      of this large membrane-bound macromolecular complex via in silico modeling.
      Cocrystallization of the cytochrome bc1 complex with the 4(1H)-pyridone class of
      inhibitors, GSK932121 and GW844520, that have been shown to be potent
      antimalarial agents in vivo, revealed that these inhibitors do not bind at the
      Q(o) site but bind at the Q(i )site. The discovery that these compounds bind at
      the Q(i) site may provide a molecular explanation for the cardiotoxicity and
      eventual failure of GSK932121 in phase-1 clinical trial and highlight the need
      for direct experimental observation of a compound bound to a target site before
      chemical optimization and development for clinical trials. The binding of the
      4(1H)-pyridone class of inhibitors to Q(i) also explains the ability of this
      class to overcome parasite Q(o)-based atovaquone resistance and provides critical
      structural information for future design of new selective compounds with improved
      safety profiles.

PMID- 25564667
TI  - Profile of Brian Charlesworth.

PMID- 25564665
TI  - Shadow enhancers enable Hunchback bifunctionality in the Drosophila embryo.
AB  - Hunchback (Hb) is a bifunctional transcription factor that activates and
      represses distinct enhancers. Here, we investigate the hypothesis that Hb can
      activate and repress the same enhancer. Computational models predicted that Hb
      bifunctionally regulates the even-skipped (eve) stripe 3+7 enhancer (eve3+7) in
      Drosophila blastoderm embryos. We measured and modeled eve expression at cellular
      resolution under multiple genetic perturbations and found that the eve3+7
      enhancer could not explain endogenous eve stripe 7 behavior. Instead, we found
      that eve stripe 7 is controlled by two enhancers: the canonical eve3+7 and a
      sequence encompassing the minimal eve stripe 2 enhancer (eve2+7). Hb
      bifunctionally regulates eve stripe 7, but it executes these two activities on
      different pieces of regulatory DNA--it activates the eve2+7 enhancer and
      represses the eve3+7 enhancer. These two "shadow enhancers" use different
      regulatory logic to create the same pattern.

PMID- 25564666
TI  - Tissue-based metabolic labeling of polysialic acids in living primary hippocampal
      neurons.
AB  - The posttranslational modification of neural cell-adhesion molecule (NCAM) with
      polysialic acid (PSA) and the spatiotemporal distribution of PSA-NCAM play an
      important role in the neuronal development. In this work, we developed a tissue
      based strategy for metabolically incorporating an unnatural monosaccharide,
      peracetylated N-azidoacetyl-D-mannosamine, in the sialic acid biochemical pathway
      to present N-azidoacetyl sialic acid to PSA-NCAM. Although significant
      neurotoxicity was observed in the conventional metabolic labeling that used the
      dissociated neuron cells, neurotoxicity disappeared in this modified strategy,
      allowing for investigation of the temporal and spatial distributions of PSA in
      the primary hippocampal neurons. PSA-NCAM was synthesized and recycled
      continuously during neuronal development, and the two-color labeling showed that
      newly synthesized PSA-NCAMs were transported and inserted mainly to the growing
      neurites and not significantly to the cell body. This report suggests a reliable
      and cytocompatible method for in vitro analysis of glycans complementary to the
      conventional cell-based metabolic labeling for chemical glycobiology.

PMID- 25564668
TI  - Examination of HER3 targeting in cancer using monoclonal antibodies.
AB  - The human EGF receptor (HER/EGFR) family of receptor tyrosine kinases serves as a
      key target for cancer therapy. Specifically, EGFR and HER2 have been repeatedly
      targeted because of their genetic aberrations in tumors. The therapeutic
      potential of targeting HER3 has long been underestimated, due to relatively low
      expression in tumors and impaired kinase activity. Nevertheless, in addition to
      serving as a dimerization partner of EGFR and HER2, HER3 acts as a key player in
      tumor cells' ability to acquire resistance to cancer drugs. In this study, we
      generated several monoclonal antibodies to HER3. Comparisons of their ability to
      degrade HER3, decrease downstream signaling, and inhibit growth of cultured
      cells, as well as recruit immune effector cells, selected an antibody that later
      emerged as the most potent inhibitor of pancreatic cancer cells grown as tumors
      in animals. Our data predict that anti-HER3 antibodies able to intercept
      autocrine and stroma-tumor interactions might strongly inhibit tumor growth, in
      analogy to the mechanism of action of anti-EGFR antibodies routinely used now to
      treat colorectal cancer patients. 

PMID- 25564669
TI  - Model-driven discovery of underground metabolic functions in Escherichia coli.
AB  - Enzyme promiscuity toward substrates has been discussed in evolutionary terms as
      providing the flexibility to adapt to novel environments. In the present work, we
      describe an approach toward exploring such enzyme promiscuity in the space of a
      metabolic network. This approach leverages genome-scale models, which have been
      widely used for predicting growth phenotypes in various environments or following
      a genetic perturbation; however, these predictions occasionally fail. Failed
      predictions of gene essentiality offer an opportunity for targeting biological
      discovery, suggesting the presence of unknown underground pathways stemming from
      enzymatic cross-reactivity. We demonstrate a workflow that couples constraint
      based modeling and bioinformatic tools with KO strain analysis and adaptive
      laboratory evolution for the purpose of predicting promiscuity at the genome
      scale. Three cases of genes that are incorrectly predicted as essential in
      Escherichia coli--aspC, argD, and gltA--are examined, and isozyme functions are
      uncovered for each to a different extent. Seven isozyme functions based on
      genetic and transcriptional evidence are suggested between the genes aspC and
      tyrB, argD and astC, gabT and puuE, and gltA and prpC. This study demonstrates
      how a targeted model-driven approach to discovery can systematically fill
      knowledge gaps, characterize underground metabolism, and elucidate regulatory
      mechanisms of adaptation in response to gene KO perturbations.

PMID- 25564671
TI  - Reply to Tan et al.: Differences between real and simulated proteins in multiple
      sequence alignments.

PMID- 25564670
TI  - Calcium waves occur as Drosophila oocytes activate.
AB  - Egg activation is the process by which a mature oocyte becomes capable of
      supporting embryo development. In vertebrates and echinoderms, activation is
      induced by fertilization. Molecules introduced into the egg by the sperm trigger
      progressive release of intracellular calcium stores in the oocyte. Calcium
      wave(s) spread through the oocyte and induce completion of meiosis, new
      macromolecular synthesis, and modification of the vitelline envelope to prevent
      polyspermy. However, arthropod eggs activate without fertilization: in the
      insects examined, eggs activate as they move through the female's reproductive
      tract. Here, we show that a calcium wave is, nevertheless, characteristic of egg
      activation in Drosophila. This calcium rise requires influx of calcium from the
      external environment and is induced as the egg is ovulated. Pressure on the
      oocyte (or swelling by the oocyte) can induce a calcium rise through the action
      of mechanosensitive ion channels. Visualization of calcium fluxes in activating
      eggs in oviducts shows a wave of increased calcium initiating at one or both
      oocyte poles and spreading across the oocyte. In vitro, waves also spread inward
      from oocyte pole(s). Wave propagation requires the IP3 system. Thus, although a
      fertilizing sperm is not necessary for egg activation in Drosophila, the
      characteristic of increased cytosolic calcium levels spreading through the egg is
      conserved. Because many downstream signaling effectors are conserved in
      Drosophila, this system offers the unique perspective of egg activation events
      due solely to maternal components. 

PMID- 25564672
TI  - Simple chained guide trees give poorer multiple sequence alignments than inferred
      trees in simulation and phylogenetic benchmarks.

PMID- 25564673
TI  - Peripheral photon and neutron doses from prostate cancer external beam
      irradiation.
AB  - Peripheral photon and neutron doses from external beam radiotherapy (EBRT) are
      associated with increased risk of carcinogenesis in the out-of-field organs;
      thus, dose estimations of secondary radiation are imperative. Peripheral photon
      and neutron doses from EBRT of prostate carcinoma were measured in Rando phantom.
      (6)LiF:Mg,Cu,P and (7)LiF:Mg,Cu,P glass-rod thermoluminescence dosemeters (TLDs)
      were inserted in slices of a Rando phantom followed by exposure to 80 Gy with 18
      MV photon four-field 3D-CRT technique. The TLDs were calibrated using 6- and 18
      MV X-ray beam. Neutron dose equivalents measured with CR-39 etch-track detectors
      were used to derive readout-to-neutron dose conversion factor for (6)LiF:Mg,Cu,P
      TLDs. Average neutron dose equivalents per 1 Gy of isocentre dose were 3.8+/-0.9
      mSv Gy(-1) for thyroid and 7.0+/-5.4 mSv Gy(-1) for colon. For photons, the
      average dose equivalents per 1 Gy of isocentre dose were 0.2+/-0.1 mSv Gy(-1) for
      thyroid and 8.1+/-9.7 mSv Gy(-1) for colon. Paired (6)LiF:Mg,Cu,P and
      (7)LiF:Mg,Cu,P TLDs can be used to measure photon and neutron doses
      simultaneously. Organs in close proximity to target received larger doses from
      photons than those from neutrons whereas distally located organs received higher
      neutron versus photon dose.

PMID- 25564674
TI  - Distress of ostracism: oxytocin receptor gene polymorphism confers sensitivity to
      social exclusion.
AB  - A single-nucleotide polymorphism on the oxytocin receptor gene (OXTR), rs53576,
      involving a guanine (G) to adenine (A) substitution has been associated with
      altered prosocial features. Specifically, individuals with the GG genotype (i.e.
      the absence of the polymorphism) display beneficial traits including enhanced
      trust, empathy and self-esteem. However, because G carriers might also be more
      socially sensitive, this may render them more vulnerable to the adverse effects
      of a negative social stressor. The current investigation, conducted among 128
      white female undergraduate students, demonstrated that relative to individuals
      with AA genotype, G carriers were more emotionally sensitive (lower self-esteem)
      in response to social ostracism promoted through an on-line ball tossing game
      (Cyberball). Furthermore, GG individuals also exhibited altered blood pressure
      and cortisol levels following rejection, effects not apparent among A carriers.
      The data support the view that the presence of the G allele not only promotes
      prosocial behaviors but also favors sensitivity to a negative social stressor. 

PMID- 25564675
TI  - A new approach to estimating trends in chlamydia incidence.
AB  - OBJECTIVES: Directly measuring disease incidence in a population is difficult and
      not feasible to do routinely. We describe the development and application of a
      new method for estimating at a population level the number of incident genital
      chlamydia infections, and the corresponding incidence rates, by age and sex using
      routine surveillance data. METHODS: A Bayesian statistical approach was developed
      to calibrate the parameters of a decision-pathway tree against national data on
      numbers of notifications and tests conducted (2001-2013). Independent beta
      probability density functions were adopted for priors on the time-independent
      parameters; the shapes of these beta parameters were chosen to match prior
      estimates sourced from peer-reviewed literature or expert opinion. To best
      facilitate the calibration, multivariate Gaussian priors on (the logistic
      transforms of) the time-dependent parameters were adopted, using the Matern
      covariance function to favour small changes over consecutive years and across
      adjacent age cohorts. The model outcomes were validated by comparing them with
      other independent empirical epidemiological measures, that is, prevalence and
      incidence as reported by other studies. RESULTS: Model-based estimates suggest
      that the total number of people acquiring chlamydia per year in Australia has
      increased by ~120% over 12 years. Nationally, an estimated 356 000 people
      acquired chlamydia in 2013, which is 4.3 times the number of reported diagnoses.
      This corresponded to a chlamydia annual incidence estimate of 1.54% in 2013,
      increased from 0.81% in 2001 (~90% increase). CONCLUSIONS: We developed a
      statistical method which uses routine surveillance (notifications and testing)
      data to produce estimates of the extent and trends in chlamydia incidence.

PMID- 25564676
TI  - 2014: signaling breakthroughs of the year.
AB  - The 2014 breakthroughs fell into four main areas: innate immunity, host-microbe
      interactions, cell death signaling, and methodological advances in the study of
      cell signaling. Nominations included new discoveries about signaling in innate
      immune cells, innate immune functions for lymphoid and nonhematological cells,
      and the importance of host-microbe interactions for the regulation of host
      physiology. Also this year, we received nominations highlighting molecular
      mechanisms by which p53 contributes to the pathology of chronic inflammation and
      how signaling pathways mediate programmed necrotic cell death. Finally, 2014 saw
      the use of new techniques to study cell signaling and identify drug targets, such
      as the in vivo use of RNA interference to study signaling in T cells and new
      computational methods to study large datasets of different data types. 

PMID- 25564679
TI  - Serum Uric Acid, Gender, and Low Ankle Brachial Index in Adults With High
      Cardiovascular Risk.
AB  - Uric acid (UA) has been reported to be associated with cardiovascular disease
      (CVD) in caucasians. However, it is unclear whether this association remains
      significant in a Chinese population. The present study aimed to investigate the
      association between UA and low ankle brachial index (ABI), a measurement of
      peripheral arterial disease, in Chinese patients. A total of 6262 hospital-based
      patients with high CVD risk were enrolled. Low ABI was defined as ABI <=0.9 in
      either side. Low ABI was detected in 1390 (22.2%) patients. Higher UA was
      significantly associated with higher risk of low ABI and modified by gender (P =
      .0045). After adjusting for age, body mass index, total cholesterol,
      triglyceride, low-density lipoprotein, high-density lipoprotein, fasting glucose,
      hypertension, and smoking, participants in the highest quartile of UA exhibited
      37% (odds ratio [OR]:1.37, 95% confidence interval [CI]: 1.03-1.82) higher risk
      of low ABI compared to those in the lowest quartile in men, while OR (95% CI) was
      1.69 (1.29-2.22) for women. However, when kidney function was further adjusted,
      the associations were attenuated in both men and women and were significant only
      in women. The results were suggestive of higher UA associating with higher risk
      of low ABI in women, and the association was largely driven by kidney function,
      especially in men. 

PMID- 25564681
TI  - The importance of sample archiving in   microbial ecology.

PMID- 25564680
TI  - One-year follow-up of zoster-associated pain in 764  immunocompetent patients
      with acute herpes zoster  treated with famciclovir (FAMILIAR study).
AB  - BACKGROUND: Herpes zoster (HZ), a reactivation of varicella zoster virus
      manifested by skin blisters and neuralgia, can lead to postherpetic neuralgia in
      10-20% of affected subjects. METHOD: In this study, a cohort of 764 patients with
      HZ was treated with 1500 mg/day of famciclovir for 7 days, and zoster-associated
      pain (ZAP) was monitored monthly thereafter for up to 12 months until pain
      resolution was achieved. Patients were questioned monthly by telephone, and pain
      was recorded using a numerical rating scale (NRS, 0-10). KEY RESULTS: A total of
      751 of 764 (98.3%) patients completed follow-up. The percentage of patients with
      ZAP was 12.4% at day 90, 7.1% at 6 months and 4.0% at 1 year. After the third
      month, the NRS were 3 or less in most of the remaining patients with ZAP.
      Stratified analysis revealed significant persistence of ZAP in patients aged >=50
      years and in those aged >=65 years, and in patients with either moderate-to
      severe skin symptoms or severe pain at the initial consultation.Stratified
      analyses unexpectedly showed patients who commenced famciclovir at 0-2 days after
      onset of the eruption had a higher prevalence of ZAP at day 90 than those treated
      at 3-5 days or >=6 days after rash onset (P = 0.0164, log-rank test). On further
      analysis, a higher proportion of patients (45.4%) treated at 0-2 days had
      moderate to severe symptoms compared with those treated at 3-5 days (40.5%) or
      >=6 days (37.0%) (P = 0.0987, Cochran-Armitage test). CONCLUSION & INFERENCE:
      This study, with an exceptionally high follow-up rate, revealed several new
      findings, including the influence of disease severity on the delay between the
      onset of symptoms and seeking medical attention. Six adverse drug reactions were
      reported in five of 721 patients in the safety analysis, including two severe
      cases of vomiting and convulsions.

PMID- 25564678
TI  - Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species
      promote cerebral artery dilation.
AB  - Reactive oxygen species (ROS) can have divergent effects in cerebral and
      peripheral circulations. We found that Ca(2+)-permeable transient receptor
      potential ankyrin 1 (TRPA1) channels were present and colocalized with NADPH
      (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2), a
      major source of ROS, in the endothelium of cerebral arteries but not in other
      vascular beds. We recorded and characterized ROS-triggered Ca(2+) signals
      representing Ca(2+) influx through single TRPA1 channels, which we called "TRPA1
      sparklets." TRPA1 sparklet activity was low under basal conditions but was
      stimulated by NOX-generated ROS. Ca(2+) entry during a single TRPA1 sparklet was
      twice that of a TRPV4 sparklet and ~200 times that of an L-type Ca(2+) channel
      sparklet. TRPA1 sparklets representing the simultaneous opening of two TRPA1
      channels were more common in endothelial cells than in human embryonic kidney
      (HEK) 293 cells expressing TRPA1. The NOX-induced TRPA1 sparklets activated
      intermediate-conductance, Ca(2+)-sensitive K(+) channels, resulting in smooth
      muscle hyperpolarization and vasodilation. NOX-induced activation of TRPA1
      sparklets and vasodilation required generation of hydrogen peroxide and lipid
      peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite
      of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated
      cerebral arteries. These data suggest that in the cerebral circulation, lipid
      peroxidation metabolites generated by ROS activate Ca(2+) influx through TRPA1
      channels in the endothelium of cerebral arteries to cause dilation. 

PMID- 25564677
TI  - The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-beta signaling.
AB  - Transforming growth factor-beta (TGF-beta) signaling regulates cell proliferation
      and differentiation, which contributes to development and disease. Upon binding
      TGF-beta, the type I receptor (TGFBRI) binds TGFBRII, leading to the activation
      of the transcription factors SMAD2 and SMAD3. Using an RNA interference screen of
      the human kinome and a live-cell reporter for TGFBR activity, we identified the
      kinase BUB1 (budding uninhibited by benzimidazoles-1) as a key mediator of TGF
      beta signaling. BUB1 interacted with TGFBRI in the presence of TGF-beta and
      promoted the heterodimerization of TGFBRI and TGFBRII. Additionally, BUB1
      interacted with TGFBRII, suggesting the formation of a ternary complex. Knocking
      down BUB1 prevented the recruitment of SMAD3 to the receptor complex, the
      phosphorylation of SMAD2 and SMAD3 and their interaction with SMAD4, SMAD
      dependent transcription, and TGF-beta-mediated changes in cellular phenotype
      including epithelial-mesenchymal transition (EMT), migration, and invasion.
      Knockdown of BUB1 also impaired noncanonical TGF-beta signaling mediated by the
      kinases AKT and p38 MAPK (mitogen-activated protein kinase). The ability of BUB1
      to promote TGF-beta signaling depended on the kinase activity of BUB1. A small
      molecule inhibitor of the kinase activity of BUB1 (2OH-BNPP1) and a kinase
      deficient mutant of BUB1 suppressed TGF-beta signaling and formation of the
      ternary complex in various normal and cancer cell lines. 2OH-BNPP1 administration
      to mice bearing lung carcinoma xenografts reduced the amount of phosphorylated
      SMAD2 in tumor tissue. These findings indicated that BUB1 functions as a kinase
      in the TGF-beta pathway in a role beyond its established function in cell cycle
      regulation and chromosome cohesion. 

PMID- 25564682
TI  - Foreword.

PMID- 25564683
TI  - Radiotherapy of morphea-type basal cell carcinoma: results  in 127 cases.
AB  - BACKGROUND: The morphea-type basal cell carcinoma (MBCC) is a rare form of basal
      cell carcinoma (BCC) with lower response to treatments than other types of
      BCC.Objective To evaluate the role of radiotherapy (RT) in the therapeutic
      strategy of MBCC. METHODS: A retrospective study was performed on 127 patients
      affected with MBCC, who underwent RT in the period 1982-2013. RT was delivered
      with conventional energies ranging from 50 to 120 kV and the administration of a
      total dose ranging from 40 to 70 Gy (mean 56.17 Gy). The irradiated fields
      included a margin of 1.5 cm around the lesion. RESULTS: The median follow-up time
      was 29 months (range 1-324 months). Complete remission was observed in 122
      patients (96.06%), partial remission in one (0.78%). Three cases were non
      responsive (2.36%). In one case (0.78%), the lesion failed to heal after RT,
      since the onset of radiodermatitis histologically ascertained. The cure rate was
      81.08% after 5 years and 78.02% after 10 years from the end of RT. Twelve cases
      relapsed (10.2%). CONCLUSION: Because of the frequent diagnostic delay and its
      ill-defined margins, MBCC is difficult to cure. Our results after 5 years from RT
      (cure rate 81.08%) are more satisfactory respect to the others reported in the
      literature (69% and 72.3%), but less good than those obtained in other forms of
      primary malignant neoplasms of the skin (92.43%). Nevertheless,we consider that
      RT plays an important role in the therapeutic strategy of MBCCs. In fact, it can
      be applied easily in elderly patients, and in peculiar localization of the
      disease (eyelid, nose and ear), without being invasive.

PMID- 25564684
TI  - Retracted: 'Response: Early-stage Hodgkin lymphoma' by M. Hudson.

PMID- 25564686
TI  - Author's reply.

PMID- 25564685
TI  - Author's reply.

PMID- 25564687
TI  - Author's reply.

PMID- 25564688
TI  - Additional thoughts on causal  inference, probability theory,  and graphical
      insights.

PMID- 25564689
TI  - Comment on 'Causal inference,  probability theory, and graphical  insights' by
      Stuart G. Baker.

PMID- 25564690
TI  - Optimizing waist circumference cut-points for the metabolic syndrome in a South
      African cohort at 3-year follow-up: the SABPA prospective cohort.

PMID- 25564692
TI  - Dentistry in the communication age.

PMID- 25564691
TI  - Effect of intrinsic nanoparticle pigmentation on the color stability of denture
      base acrylic resins.
AB  - STATEMENT OF PROBLEM: Intrinsic pigmentation is widely used to improve the
      esthetic features of denture base acrylic resins. However, acrylic resin may
      discolor over time. PURPOSE: The purpose of this study was to investigate the
      effect of intrinsic nanoparticle pigmentation on the color stability of acrylic
      resins. MATERIAL AND METHODS: The acrylic resins, Onda Cryl, QC 20, Classico, and
      Lucitone, were evaluated. Twenty-one disk-shaped specimens (3 * 30 mm) were
      fabricated from each acrylic resin. Seven were colored with 3% Poli-Cor intrinsic
      pigment used to color denture base, 7 were colored with 7% pigment, and 7 were
      not pigmented. In addition, 7 specimens were fabricated containing only pigment.
      The specimens were thermally cycled 2000 times between 5 degrees C and 55 degrees
      C with a 30-second dwell time at each temperature. The specimen colors were
      measured with a spectrophotometer and evaluated with the CIE L*a*b* system before
      (B) and after thermal cycling (T). The pigment morphology was analyzed by using a
      scanning electron microscope (SEM) and energy-dispersive x-ray spectroscopy (EDS)
      techniques. The results were analyzed with 2-way nested ANOVA and Tukey HSD tests
      (alpha=.05). RESULTS: Classico acrylic resin with and without pigment underwent
      the least color change, followed in order by Lucitone, Onda Cryl, and QC-20. The
      presence of pigments reduced the color change of the acrylic resins significantly
      (P<.05) for the specimens containing 7% pigment (0.32 +/-0.18 DeltaE). Titanium
      was the sole metallic component present in the pigment, probably in the oxide
      form (TiO2). CONCLUSIONS: Nanoparticle pigments enhanced the color stability of
      denture base acrylic resins.

PMID- 25564693
TI  - Macrolides and the placenta--author's response.

PMID- 25564694
TI  - [In process citation].

PMID- 25564695
TI  - Intriguing model significantly reduces boarding of psychiatric patients, need for
      inpatient hospitalization.
AB  - As new approaches to the care of psychiatric emergencies emerge, one solution is
      gaining particular traction. Under the Alameda model, which has been put into
      practice in Alameda County, CA, patients who are brought to regional EDs with
      emergency psychiatric issues are quickly transferred to a designated emergency
      psychiatric facility as soon as they are medically stabilized. This alleviates
      boarding problems in area EDs while also quickly connecting patients with
      specialized care. With data in hand on the model's effectiveness, developers
      believe the approach could alleviate boarding problems in other communities as
      well. The model is funded by through a billing code established by California's
      Medicaid program for crisis stabilization services. Currently, only 22% of the
      patients brought to the emergency psychiatric facility ultimately need to be
      hospitalized; the other 78% are able to go home or to an alternative situation.
      In a 30-day study of the model, involving five community hospitals in Alameda
      County, CA, researchers found that ED boarding times were as much as 80% lower
      than comparable ED averages, and that patients were stabilized at least 75% of
      the time, significantly reducing the need for inpatient hospitalization.

PMID- 25564696
TI  - Study: new approach to handoffs slashes errors, preventable adverse events; other
      medical centers move to implement the protocol.
AB  - A new approach to hospital handoffs has shown it can significantly reduce medical
      errors as well as preventable adverse events. The approach, dubbed the I-PASS
      bundle, uses a mnemonic to alert providers to all the issues that need to be
      covered during a handoff, but also includes a written handoff tool, communication
      training, a sustainability campaign, and a process for feedback. In a study of
      the I-PASS bundle conducted at nine pediatric hospitals, investigators found that
      the approach reduced medical errors by 23%, and the rate of preventable adverse
      events by 30%. Investigators say I-PASS did not increase the amount of time
      required to conduct a handoff. On average, handoffs in the study took 2.5 minutes
      per patient. Several medical centers are now implementing the approach hospital
      wide, and additional studies into the approach are planned. Developers advise
      hospitals interested in the approach to first gather data and survey providers to
      make a case for the intervention.

PMID- 25564697
TI  - The Joint Commission: hospitals make strides on core measures with more achieving
      "top performer" status.
AB  - Performance on key quality measures continues to improve at more than 3,300
      accredited hospitals, according to new data from The Joint Commission (TJC). In
      its 2014 annual report, the Oakbrook Terrace, IL, accrediting agency, said that
      more than a third of the country's accredited hospitals are now top performers in
      TJC's core measures program. This is a marked increase from 2002 when the top
      performer program was first initiated and just 7% of hospitals achieved top
      performer status on a much smaller range of quality metrics. To be recognized as
      a top performer, TJC stipulates that hospitals must achieve a cumulative
      performance of 95% or greater on all reported accountability measures, achieve a
      performance of 95% or greater on every accountability measure where there are at
      least 30 denominator cases, and have at least one core measure set that has a
      composite rate of at least 95%--and all metrics within that measure set must rank
      at 95% or above as well. The number of academic medical centers recognized as top
      performers grew from 24, recognized in last year's annual report, to 35 in the
      2014 report, now representing 29% of all accredited academic medical centers.
      Only 11% of the top performing hospitals were public hospitals, designated as
      "government owned" in the annual report. The TJC suggests that this indicates
      that performance improvement needs to be prioritized at these hospitals. TJC is
      providing special recognition to 44 top performing hospitals that went beyond the
      minimum requirements, reporting on five or more sets of measures, and achieved
      top performer recognition on that expanded set of measures.

PMID- 25564698
TI  - 2014 Salary Survey results ED Management. With an economy on the mend, nurses see
      modest pay hikes; strong demand for EPs puts upward pressure on compensation
      packages.

PMID- 25564699
TI  - Polymorphism of resorcinol explored by complementary vibrational spectroscopy (FT
      RS, THz-TDS, INS) and first-principles solid-state computations (plane-wave DFT).
AB  - The polymorphism of resorcinol has been complementary studied by combining Raman,
      time-domain terahertz, and inelastic neutron scattering spectroscopy with modern
      solid-state density functional theory (DFT) calculations. The spectral
      differences, emerging from the temperature-induced structural phase transition,
      have been successfully interpreted with an emphasis on the low-wavenumber range.
      The given interpretation is based on the plane-wave DFT computations, providing
      an excellent overall reproduction of both wavenumbers and intensities and
      revealing the source of the observed spectral differences. The performance of the
      generalized gradient approximation (GGA) functionals in prediction of the
      structural parameters and the vibrational spectra of the normal-pressure
      polymorphs of resorcinol has been extensively examined. The results show that the
      standard Perdew, Burke, and Ernzerhof (PBE) approach along with its "hard"
      revised form tends to be superior if compared to the "soft" GGA approximation. 

PMID- 25564702
TI  - Access to Calpha backbone dynamics of biological solids by 13C T1 relaxation and
      molecular dynamics simulation.
AB  - We introduce a labeling scheme for magic angle spinning (MAS) solid-state NMR
      that is based on deuteration in combination with dilution of the carbon spin
      system. The labeling strategy achieves spectral editing by simplification of the
      HalphaCalpha and aliphatic side chain spectral region. A reduction in both proton
      and carbon spin density in combination with fast spinning (>=50 kHz) is essential
      to retrieve artifact-free (13)C-R1 relaxation data for aliphatic carbons. We
      obtain good agreement between the NMR experimental data and order parameters
      extracted from a molecular dynamics (MD) trajectory, which indicates that carbon
      based relaxation parameters can yield complementary information on protein
      backbone as well as side chain dynamics. 

PMID- 25564701
TI  - Effects of oleanolic acid on the insulin signaling pathway in skeletal muscle of
      streptozotocin-induced diabetic male Sprague-Dawley rats.
AB  - BACKGROUND: The pant-derived triterpene oleanolic acid (OA) has been shown to
      have antidiabetic effects, but its action on the insulin signaling cascade has
      not been fully elucidated. The aim of the present study was to investigate the
      effects of OA on aspects of the phosphatidylinositol 3-kinase/Akt insulin
      signaling cascade in skeletal muscle of streptozotocin-induced type 1 diabetic
      male Sprague-Dawley rats. METHODS: Diabetic and non-diabetic rats were treated
      with insulin (4 IU/kg), OA (80 mg/kg), and the combination of OA + insulin in
      acute 60-min and sub-chronic 14-day studies. Single and daily doses were
      administered in the acute and sub-chronic studies, respectively. In acute
      studies, phosphorylated (p-) Akt and p-glycogen synthase (GS) expression was
      evaluated. In sub-chronic studies, GS and glycogen phosphorylase (GP) expression
      and activity were evaluated, as were glycogen levels. RESULTS: The findings show
      that OA enhances insulin-stimulated hypoglycemic effects in diabetic rats. In the
      acute study, OA increased levels of p-Akt and decreased levels of p-GS. In the
      sub-chronic study, OA increased both GS and GP activity, whereas OA + insulin
      increased GS and decreased GP activity. Treatment of rats with OA and OA +
      insulin increased GS expression in the skeletal muscle of diabetic rats and
      decreased GP expression. Glycogen levels were increased by OA but decreased OA +
      insulin treatment. CONCLUSION: Oleanolic acid in synergy with insulin can enhance
      activation of the insulin signaling pathway. Furthermore, the present study
      provides evidence of OA activation of insulin signaling enzymes independent of
      insulin.

PMID- 25564700
TI  - Immunomodulation of RAW 264.7 murine macrophage functions and antioxidant
      activities of 11 plant extracts.
AB  - A group of 11 medicinal plants, including Lavandula pubescens, Trigonella
      foenugricium, Salsola schweinforthi, Calligonum comosum, Silene succulenta,
      Silene villosa, Bogonvillea glabra, Cakile maritime, Gomphrene celesoids,
      Mirabilis jalaba, and Silene nocturna growing in Egypt, were extracted and
      examined for their immunomodulatory and antioxidant activities. RAW 264.7 cells
      were recruited to investigate the immunomodulatory effect through multiple
      parameters analysis. First, the proliferation index of macrophages cells was
      evaluated revealing that Trigonella foenugricium, Silene succulenta and Silene
      villosa have a significant cytotoxic effect on RAW cells. Interestingly, we
      observed enhancement of macrophages phagocytic function of by all extracts except
      Cakile maritime, Gomphrena celosioides and Silene nocturna. Afterwards,
      macrophages were challenged by incubation with LPS and the effect of various
      extracts on inflammatory responses was investigated; the generation of NO from
      activated macrophage was substantially suppressed by 7 extracts namely,
      Trigonella foenugricium, Calligonum comosum, Silene succulenta, Bougainvillea
      glabra, Mirabilis jalaba, Gomphrena celosioides and Silene nocturna. TNF-alpha
      was decreased by percentage range from 3.8 to 85.8% and Trigonella foenugricium
      extract showed the highest inhibition of TNF-alpha release. All extracts except
      Trigonella foenugricium, Salsola schweinforthi, Silene succulenta and Mirabilis
      jalaba significantly inhibited COX-2 production from stimulated macrophage.
      Moreover, evaluating the potential antioxidant activity of these extracts showed
      that Trigonella foenugricium, Salsola schweinforthi, Calligonum comosum,
      Bogonvillea glabra and Mirabilis jalaba exhibited some antioxidant activities.
      Taken together, our results suggest that some of these extracts may have a
      considerable antinflammatory and antioxidant effects and may be a potential
      therapeutic choice in the treatment of inflammatory diseases. 

PMID- 25564703
TI  - Ambient synthesis of dienals via triazole-gold and amine catalysis relay.
AB  - A highly efficient synthesis of substituted conjugated dienals was developed
      through a triazole-gold (TA-Au)-catalyzed propargyl vinyl ether rearrangement
      followed by an amine catalyzed allene-aldehyde tautomerization. Various
      substituted vinylogous aldehydes were prepared in one pot with good to excellent
      yields (up to 95%) under mild conditions with high atom economy. 

PMID- 25564705
TI  - A historical and undergraduate context to inform interprofessional education for
      global health.
AB  - Through a case example of fluoride, this paper examines why dental caries and
      other 21st century challenges require collaborative practice toward improved
      health that begins with interprofessional education (IPE). We suggest a
      theoretical framework for expanding the thinking around IPE for global health and
      recommend beginning at the undergraduate, or "pre-interprofessional," level where
      students are still undifferentiated by profession. Our theoretical framework can
      assist in providing a foundation for curriculum alignment and calibration moving
      forward to the graduate and professional training levels. 

PMID- 25564706
TI  - Envisioning a transdisciplinary university.
AB  - Achieving social and economic growth requires collaboration, especially in global
      health. If universities are to improve health globally, they will need to train
      students and to support faculty who can effectively collaborate with those from
      other disciplines and cultures. 

PMID- 25564707
TI  - Identifying global health competencies to prepare 21st century global health
      professionals: report from the global health competency subcommittee of the
      consortium of universities for global health.
AB  - As universities increase their focus on global health-related professional
      education, the need for specific competencies and outcomes to guide curriculum
      development is urgent. To address this need, the chair of the Education Committee
      of the Consortium of Universities for Global Health (CUGH) appointed a
      Subcommittee to determine if there is a need for broad global health core
      competencies applicable across disciplines, and if so, what those competencies
      should be. Based on that work, this paper (a) discusses the benefits of
      developing interprofessional and discipline-specific global health competencies;
      (b) highlights themes that emerged from a preliminary review of existing related
      literature; and (c) reviews the process used to identify two levels of
      interprofessional global health competencies. 

PMID- 25564708
TI  - Towards defining interprofessional competencies for global health education:
      drawing on educational frameworks and the experience of the UW-Madison Global
      Health Institute.
AB  - The experience and lessons to date from the University of Wisconsin-Madison
      Global Health Institute's global health programs, considered together with more
      recently published competency frameworks related to global health practice, can
      provide important insights into the development of a core set of
      interprofessional competencies for global health that can be used across
      disciplines and professions. 

PMID- 25564709
TI  - Relationships matter: the role for social-emotional learning in an
      interprofessional global health education.
AB  - As global health curricula and competencies are defined, the instructional
      foundation of practice-based learning and soft skills training requires
      reexamination. This paper explores the integration of social-emotional
      instruction into global health education, specifically highlighting its role in
      interprofessional learning environments. One method to teach the core
      competencies in the higher education context is through restorative practices.
      Restorative practices is a "social science that integrates developments from a
      variety of disciplines and fields in order to build healthy communities, increase
      social capital, decrease crime and antisocial behavior, repair harm and restore
      relationships." The restorative philosophy incorporates the core competencies of
      socio-emotional learning and views conflict as an opportunity for learning. The
      first part discusses the foundations of social-emotional learning (SEL). It then
      explores the applicability of SEL in interprofessional and global health
      education. 

PMID- 25564710
TI  - The creation of an institutional commons: institutional and individual benefits
      and risks in global health interprofessional education.
AB  - The World Health Organization and others recognize interprofessional
      collaboration as an effective strategy toward mitigating the global health
      workforce crisis. The authors describe challenges to developing sustainable
      interprofessional education and practice programs and suggest a framework to
      address them. 

PMID- 25564711
TI  - Organizational learning and the development of global health educational
      capabilities: critical reflections on a decade of practice.
AB  - This paper describes the process of organizational global health capability
      development at the University of Maryland Baltimore over the past decade.
      Theories of organizational learning and of organizational capabilities are
      applied in this retrospective analysis of organizational innovations in global
      health education within UMB as well as in the University of Maryland School of
      Nursing. 

PMID- 25564712
TI  - Interprofessional education: a theoretical orientation incorporating profession
      centrism and social identity theory.
AB  - To improve health for our citizens our health work force must be team focused and
      collaboration ready. The theory of social identity is used to explain profession
      centrism and ultimately inform our understanding of the challenges of developing
      and implementing interprofessional education curricula. 

PMID- 25564713
TI  - Using experiential learning to develop interprofessional skills in global health:
      perspectives from the O'NeillInstitute for National and Global Health Law.
AB  - Research centers at universities, such as the O'Neill Institute for National and
      Global Health Law at Georgetown University (the O'Neill Institute), are uniquely
      positioned to facilitate interprofessional collaboration, and to educate current
      and future global health practitioners. This paper will discuss the O'Neill
      Institute's experience in developing interprofessional global health skills
      through its practicum courses. The O'Neill Institute has found that practicum
      style courses help foster three fundamental elements of interprofessional
      collaboration in global health: (1) the ability to define professional roles and
      responsibilities in a project; (2) interprofessional communication skills; and
      (3) the ability to work in an interprofessional team. 

PMID- 25564714
TI  - In vitro and in vivo conditional sensitization of hepatocellular carcinoma cells
      to TNF-induced apoptosis by taxol.
AB  - High mortality among hepatocellular carcinoma (HCC) patients reflects both late
      diagnosis and low curability, due to pharmacoresistance. Taxol (TAX) is toxic for
      many human HCC-derived cell lines, yet its clinical efficacy on HCCs is poor.
      Combining TAX with other drugs appears a promising possibility to overcome such
      refractoriness. We analyzed whether combining tumor necrosis factor (TNF) with
      TAX would improve their toxicity. Human HCC-derived cell lines were treated with
      TAX or TNF, alone or combined. Apoptosis was assessed by morphology and flow
      cytometry. Several pro- and anti-apoptotic molecules were evaluated by western
      blotting and/or enzymatic assay. After a 24 hour treatment, TNF was ineffective
      and TAX modestly cytotoxic, whereas HCC cells were conditionally sensitized to
      TNF by TAX. Indeed some relevant parameters were shifted to a prodeath setting:
      TNF-receptor 1 was increased, SOCS3, c-FLIP and pSTAT3 were markedly
      downregulated. These observations provide a significant clue to critically
      improve the drug susceptibility of HCC cells by combining 2 agents, TAX and TNF.
      The sequential application of TAX at a low dosage followed by TNF for only a
      short time triggered a strong apoptotic response. Of interest, prior TAX
      administration could also sensitize to TNF-induced apoptosis in the Yoshida AH
      130 hepatoma transplanted in mice. Therefore, scrutinizing the possibility to
      develop similar combination drug regimens in suitable preclinical models seems
      highly advisable. 

PMID- 25564715
TI  - Single thrombopoietin dose alleviates hematopoietic stem cells intrinsic short-
      and long-term ionizing radiation damage. In vivo identification of anatomical
      cell expansion sites.
AB  - Hematopoietic stem cells (HSC) are essential for maintaining the integrity of
      complex and long-lived organisms. HSC, which are self-renewing, reconstitute the
      hematopoietic system through out life and facilitate long-term repopulation of
      myeloablated recipients. We have previously demonstrated that when mice are
      exposed to sublethal doses of ionizing radiation, subsets of the stem/progenitor
      compartment are affected. In this study we examine the role of thrombopoietin
      (TPO) on the regenerative capacities of HSC after irradiation and report the
      first demonstration of efficacy of a single injection of TPO shortly after in
      vivo exposure to ionizing radiation for reducing HSC injury and improving their
      functional outcome. Our results demonstrate that TPO treatment not only reduced
      the number of apoptotic cells but also induced a significant modification of
      their intrinsic characteristics. These findings were supported by transplantation
      assays with long-term HSC that were irradiated or unirradiated, TPO treated or
      untreated, in CD45.1/CD45.2 systems and by using luciferase-labeled HSC for
      direct bioluminescence imaging in living animals. Of particular importance, our
      data demonstrate the skull to be a highly favorable site for the TPO-induced
      emergence of hematopoietic cells after irradiation, suggesting a TPO-mediated
      relationship of primitive hematopoietic cells to an anatomical component.
      Together, the data presented here: provide novel findings about aspects of TPO
      action on stem cells, open new areas of investigation for therapeutic options in
      patients who are treated with radiation therapy, and show that early
      administration of a clinically suitable TPO-agonist counteracts the previously
      observed adverse effects.

PMID- 25564717
TI  - The effect of ionizing radiation on mRNA levels of the DNA damage response genes
      rad9, rad1 and hus1 in various mouse tissues.
AB  - Rad9, Rad1 and Hus1 are essential genes conserved from yeast to humans. They form
      a heterotrimer complex (9-1-1 complex) that participates in the cell cycle
      checkpoint activation and DNA damage repair in eukaryotic cells. Rad9, Rad1 and
      Hus1 deficient cells are hypersensitive to ionizing radiation and mouse cells
      deleted for anyone of the three genes are highly sensitive to the killing by
      gamma rays. We propose that ionizing radiation-induced transcription of these
      genes is a mechanism by which cells respond to radiation-induced damage. In this
      study we used quantitative real-time RT-PCR(qPCR) to analyze the mRNA levels of
      Rad9, Rad1 and Hus1 in various tissues isolated from mice that were either mock
      irradiated or exposed to 10 Gy gamma radiation. Our results indicated that the
      mRNA levels of Rad9, Rad1 and Hus1 genes were very different among these tissues,
      and we found high natural levels of mRNA in the spleen, lung, ovary and testis of
      mice before exposure to radiation. The mRNA levels of the three genes were well
      correlated across these tissues, being high, medium or low in each of the tissues
      simultaneously. The mRNA levels of the three genes were analyzed at 2, 6, 12, 24
      and 48 h after irradiation. In most tissues Rad9 was strongly induced at 2 and 12
      h time points and Hus1 was strongly induced at 2, 12 and 48 h time points, but
      Rad1 was minimally induced in most of the tissues with the exception of slightly
      higher levels in the heart and lung tissues at the 48 h time point. These results
      suggest that the regulation mechanisms for the mRNA levels of the three genes in
      response to ionizing radiation are complex and not well orchestrated. We also
      detected the induction of Rad9 and Hus1 proteins in the heart and liver of the
      animals after irradiation, and found that Rad9 protein levels were highly induced
      in both the heart and liver, while the Hus1 protein levels were significantly
      induced only in the liver, suggesting that Rad9 and Hus1 protein levels are not
      regulated in a coordinated manner in response to irradiation. We then went on to
      measure the mRNA levels of the three genes and the Rad9 and Hus1 protein levels
      in the mouse liver cell line (NCTC 1469) in response to irradiation in vitro. All
      three genes in the cultured cells were minimally induced at mRNA level, obviously
      different from the highly dynamic induction in liver. Rad9 and Hus1 were
      significantly induced at the protein level, but the induced Rad9 protein levels
      were higher than the Hus1 levels. Taken together, the good correlation of the
      mRNA levels of Rad9, Hus1 and Rad1 genes across different tissues isolated from
      the animals that were mock irradiated and the lack of correlation in mRNA as well
      as protein levels after irradiation suggest that the 9-1-1 complex has evolved to
      play various physiological roles in tissues rather than dealing with high doses
      of gamma radiation or other genotoxic agents.

PMID- 25564716
TI  - Interleukin-12 preserves the cutaneous physical and immunological barrier after
      radiation exposure.
AB  - The United States continues to be a prime target for attack by terrorist
      organizations in which nuclear detonation and dispersal of radiological material
      are legitimate threats. Such attacks could have devastating consequences to large
      populations, in the form of radiation injury to various human organ systems. One
      of these at risk organs is the cutaneous system, which forms both a physical and
      immunological barrier to the surrounding environment and is particularly
      sensitive to ionizing radiation. Therefore, increased efforts to develop medical
      countermeasures for treatment of the deleterious effects of cutaneous radiation
      exposure are essential. Interleukin-12 (IL-12) was shown to elicit protective
      effects against radiation injury on radiosensitive systems such as the bone
      marrow and gastrointestinal tract. In this article, we examined if IL-12 could
      protect the cutaneous system from a combined radiation injury in the form of
      sublethal total body irradiation and beta-radiation burn (beta-burn) directly to
      the skin. Combined radiation injury resulted in a breakdown in skin integrity as
      measured by transepidermal water loss, size of beta-burn lesion and an
      exacerbated loss of surveillant cutaneous dendritic cells. Interestingly,
      intradermal administration of IL-12 48 h postirradiation reduced transepidermal
      water loss and burn size, as well as retention of cutaneous dendritic cells. Our
      data identify IL-12 as a potential mitigator of radiation-induced skin injury and
      argue for the further development of this cytokine as a radiation countermeasure.

PMID- 25564719
TI  - Understanding cancer development processes after HZE-particle exposure: roles of
      ROS, DNA damage repair and inflammation.
AB  - During space travel astronauts are exposed to a variety of radiations, including
      galactic cosmic rays composed of high-energy protons and high-energy charged
      (HZE) nuclei, and solar particle events containing low- to medium-energy protons.
      Risks from these exposures include carcinogenesis, central nervous system damage
      and degenerative tissue effects. Currently, career radiation limits are based on
      estimates of fatal cancer risks calculated using a model that incorporates human
      epidemiological data from exposed populations, estimates of relative biological
      effectiveness and dose-response data from relevant mammalian experimental models.
      A major goal of space radiation risk assessment is to link mechanistic data from
      biological studies at NASA Space Radiation Laboratory and other particle
      accelerators with risk models. Early phenotypes of HZE exposure, such as the
      induction of reactive oxygen species, DNA damage signaling and inflammation, are
      sensitive to HZE damage complexity. This review summarizes our current
      understanding of critical areas within the DNA damage and oxidative stress arena
      and provides insight into their mechanistic interdependence and their usefulness
      in accurately modeling cancer and other risks in astronauts exposed to space
      radiation. Our ultimate goals are to examine potential links and crosstalk
      between early response modules activated by charged particle exposure, to
      identify critical areas that require further research and to use these data to
      reduced uncertainties in modeling cancer risk for astronauts. A clearer
      understanding of the links between early mechanistic aspects of high-LET response
      and later surrogate cancer end points could reveal key nodes that can be
      therapeutically targeted to mitigate the health effects from charged particle
      exposures.

PMID- 25564720
TI  - Localization estimation of ionizing radiation-induced abasic sites in DNA in the
      solid state using fluorescence resonance energy transfer.
AB  - Clustered DNA damage is considered an important factor in determining the
      biological consequences of ionizing radiation. In this study, we successfully
      estimated the localization of abasic sites (APs) in DNA exposed to ionizing
      radiation using fluorescence resonance energy transfer (FRET) without any
      involvement of repair enzyme functions. A linearized plasmid (pUC19 digested by
      Sma I) was irradiated with: (60)Co gamma rays; (4)He(2+) (2.0 MeV/u) particles;
      and the (12)C(5+) (0.37 MeV/u) particles in the solid state. A donor or acceptor
      fluorescent probe with a nucleophilic O-amino group was used to label APs. The
      results showed that the (12)C(5+) particle likely produced close APs within a
      track. The apparent distance calculated from the observed FRET efficiency (E) of
      around 0.10 was estimated to be approximately 17 base pairs. On the other hand, E
      values of (60)Co gamma rays and the (4)He(2+) beam were less than those of the
      (12)C(5+) beam, increased with increasing AP density (the average number of APs
      per base pair), and were slightly greater than those of randomly distributed APs.
      We propose that the FRET method provides a degree of localization regardless of
      whether an AP cluster is single-stranded or bistranded DNA damage.

PMID- 25564718
TI  - Drug metabolism and homologous recombination repair in radiosensitization with
      gemcitabine.
AB  - Gemcitabine (difluorodeoxycytidine; dFdCyd) is a potent radiosensitizer, noted
      for its ability to enhance cytotoxicity with radiation at noncytotoxic
      concentrations in vitro and subchemotherapeutic doses in patients.
      Radiosensitization in human tumor cells requires dFdCyd-mediated accumulation of
      cells in S phase with inhibition of ribonucleotide reductase, resulting in >=80%
      deoxyadenosine triphosphate (dATP) depletion and errors of replication in DNA.
      Less is known of the role of specific DNA replication and repair pathways in the
      radiosensitization mechanism. Here the role of homologous recombination (HR) in
      relationship to the metabolic and cell cycle effects of dFdCyd was investigated
      using a matched pair of CHO cell lines that are either proficient (AA8 cells) or
      deficient (irs1SF cells) in HR based on expression of the HR protein XRCC3. The
      results demonstrated that the characteristics of radiosensitization in the rodent
      AA8 cells differed significantly from those in human tumor cells. In the AA8
      cells, radiosensitization was achieved only under short (<=4 h) cytotoxic
      incubations, and S-phase accumulation did not appear to be required for
      radiosensitization. In contrast, human tumor cell lines were radiosensitized
      using noncytotoxic concentrations of dFdCyd and required early S-phase
      accumulation. Studies of the metabolic effects of dFdCyd demonstrated low dFdCyd
      concentrations did not deplete dATP by >=80% in AA8 and irs1SF cells. However, at
      higher concentrations of dFdCyd, failure to radiosensitize the HR-deficient
      irs1SF cells could not be explained by a lack of dATP depletion or lack of S
      phase accumulation. Thus, these parameters did not correspond to dFdCyd
      radiosensitization in the CHO cells. To evaluate directly the role of HR in
      radiosensitization, XRCC3 expression was suppressed in the AA8 cells with a
      lentiviral-delivered shRNA. Partial XRCC3 suppression significantly decreased
      radiosensitization [radiation enhancement ratio (RER) = 1.6 +/- 0.15], compared
      to nontransduced (RER = 2.7 +/- 0.27; P = 0.012), and a substantial decrease
      compared to nonspecific shRNA-transduced (RER = 2.5 +/- 0.42; P = 0.056) AA8
      cells. Although the results support a role for HR in radiosensitization with
      dFdCyd in CHO cells, the differences in the underlying metabolic and cell cycle
      characteristics suggest that dFdCyd radiosensitization in the nontumor-derived
      CHO cells is mechanistically distinct from that in human tumor cells.

PMID- 25564722
TI  - Sleep duration and health correlates among university students in 26 countries.
AB  - The aim of this study was to investigate sleep duration and its health correlates
      in university students from 26 low-, middle- and high-income countries. Using
      anonymous questionnaires and anthropometric measurements, data were collected
      from 19417 undergraduate university students (mean age 20.8, SD = 2.8) from 27
      universities from 26 countries across Asia, Africa and the Americas. Results
      indicate that the average number of self-reported hours of sleep was 7.07 (CI =
      7.04-7.09), with the prevalence of reporting <= 6, 7-8, and >= 9 h sleep duration
      of 39.2, 46.9, and 13.9%, respectively. Multinomial logistic regression found
      that sociodemographic variables, health risk behaviour and health status
      variables were found to be associated with short and long sleep duration.

PMID- 25564721
TI  - Low- and high-LET radiation drives clonal expansion of lung progenitor cells in
      vivo.
AB  - Abundant populations of epithelial progenitor cells maintain the epithelium along
      the proximal-to-distal axis of the airway. Exposure of lung tissue to ionizing
      radiation leads to tissue remodeling and potential cancer initiation or
      progression. However, little is known about the effects of ionizing radiation on
      airway epithelial progenitor cells. We hypothesized that ionizing radiation
      exposure will alter the behavior of airway epithelial progenitor cells in a
      radiation dose- and quality-dependent manner. To address this hypothesis, we
      cultured primary airway epithelial cells isolated from mice exposed to various
      doses of 320 kVp X ray or 600 MeV/nucleon (56)Fe ions in a 3D epithelial
      fibroblast co-culture system. Colony-forming efficiency of the airway epithelial
      progenitor cells was assessed at culture day 14. In vivo clonogenic and
      proliferative potentials of airway epithelial progenitor cells were measured
      after exposure to ionizing radiation by lineage tracing and IdU incorporation.
      Exposure to both X rays and (56)Fe resulted in a dose-dependent decrease in the
      ability of epithelial progenitors to form colonies in vitro. In vivo evidence for
      increased clonogenic expansion of epithelial progenitors was observed after
      exposure to both X rays and (56)Fe. Interestingly, we found no significant
      increase in the epithelial proliferative index, indicating that ionizing
      radiation does not promote increased turnover of the airway epithelium.
      Therefore, we propose a model in which radiation induces a dose-dependent
      decrease in the pool of available progenitor cells, leaving fewer progenitors
      able to maintain the airway long-term. This work provides novel insights into the
      effects of ionizing radiation exposure on airway epithelial progenitor cell
      behavior.

PMID- 25564723
TI  - Titania coated upconversion nanoparticles for near-infrared light triggered
      photodynamic therapy.
AB  - Because of the limited penetration depth of visible light that generally excites
      most of the available photosensitizers (PSs), conventional photodynamic therapy
      (PDT) is limited to the treatment of superficial and flat lesions. Recently, the
      application of deep penetrating near-infrared (NIR) light excitable upconversion
      nanoparticles (UCNs) in conjunction with PDT has shown to have clear potential in
      the treatment of solid tumors due to its ability to penetrate thick tissue.
      However, various constructs developed so far have certain limitations such as
      poor or unstable PS loading, reducing their therapeutic efficacy and limiting
      their application to solution or cell-based studies. In this work, we present a
      method to fabricate uniform core-shell structured nanoconstruct with a thin layer
      of photocatalyst or PS-titanium dioxide (TiO2) stably coated on individual UCN
      core. Our design allows controllable and highly reproducible PS loading,
      preventing any leakage of PS compared to previously developed nanoconstructs,
      thus ensuring repeatable PDT results. Further surface modification of the
      developed nanoconstructs with polyethylene glycol (PEG) rendered them
      biocompatible, demonstrating good therapeutic efficacy both in vitro and in vivo.

PMID- 25564724
TI  - Determinants of the competing outcomes of intrauterine infection, abruption, or
      spontaneous preterm birth after preterm premature rupture of membranes.
AB  - OBJECTIVE: Patients with PPROM are at risk for a variety of outcomes, including
      chorioamnionitis (CA), placental abruption (PA), or preterm labor (PTL).
      Competing risk regression can analyze a cohort's risk of individual outcomes
      while accounting for ongoing deliveries secondary to competing events. METHODS: A
      secondary analysis of the subjects from MFMU BEAM study of neuroprotection after
      preterm birth (BEAM) with conservative PPROM management. Deliveries were
      categorized as: PA, CA, PTL, "elective" or "indicated". The association between
      outcomes of PA, CA or PTL and clinical predictors of twins, ethnicity, parity,
      gestational age at rupture, bleeding, contractions, cervical dilation, preterm
      birth history, weight, and genitourinary infections were evaluated via competing
      risk regression. RESULT: 1970 subjects were included. The significance and
      directionality of predictors varied according to specific outcomes. Patients with
      twins had an increased PTL hazard (1.85) though reductions in CA- (0.66) or PA
      specific (0.56) hazards. Decreased latency in African-Americans was almost
      entirely due to an increased CA hazard (1.44) without a significant association
      with PTL. Increasing gestational age at membrane rupture was associated with a
      decreasing hazard of CA although increasing hazard of PTL. CONCLUSIONS: For
      patients with PPROM, the hazards associated with different clinical predictors
      vary according to exact outcomes.

PMID- 25564725
TI  - Toxoplasmosis-associated abortion and stillbirth in Tehran, Iran.
AB  - OBJECTIVES: This study was aimed to evaluate the role of toxoplasmosis in
      etiology of abortion and stillbirth based on molecular and serological
      techniques. MATERIAL AND METHODS: A total of 110 pregnant women with abortion and
      stillbirth were enrolled as the case group, and 110 pregnant women with normal
      delivery were enrolled as the control group. Serological and molecular detections
      of Toxoplasma gondii were assessed by ELISA and PCR methods. RESULTS: The
      seroprevalence of IgG was 25.5% in the case group (26.8% in abortion and 21.4% in
      stillbirth) and 26.4% in the control group. IgM seropositivity was detected in
      2.7% of the case group (3.6% in abortion and 0% in stillbirth) and 0.9% of the
      control group (p = 0.37). Toxoplasma gondii DNA was detected in 6.4% of the case
      group (7.3% in abortion and 3.6% in stillbirth) and 1.8% of the control group by
      PCR (p = 0.17). The major risk factor of congenital toxoplasmosis was the history
      of eating undercooked meat (p = 0.06). CONCLUSION: Results of this study revealed
      that the rate of PCR positive in women with abortion and stillbirth was 3.7 times
      higher than that in normal delivery, but the difference was not statistically
      significant. These findings suggest that toxoplasmosis can be involved in
      etiology of abortion and stillbirth.

PMID- 25564726
TI  - Ni2P nanosheets/Ni foam composite electrode for long-lived and pH-tolerable
      electrochemical hydrogen generation.
AB  - The continuous consumption of fossil fuels and accompanying environmental
      problems are driving the exploration of low-cost and effective electrocatalysts
      to produce clean hydrogen. A Ni2P nanosheets/Ni foam composite, as a non-noble
      metal electrocatalyst, has been prepared through a facile chemical conversion
      pathway using surface oxidized Ni foam as precursor and low concentration of
      trioctylphosphine (TOP) as a phosphorus source. Further investigation shows the
      oxidized layer of Ni foam can orient the formation of Ni2P nanosheets and
      facilitate the reaction with TOP. The Ni2P/Ni, acting as a robust 3D self
      supported superaerophobic hydrogen-evolving cathode, shows superior catalytic
      performance, stability, and durability in aqueous media over a wide pH value of 0
      14, making it a versatile catalyst system for hydrogen generation. Such highly
      active, stable, abundant, and low-cost materials hold enormously promising
      potential applications in the fields of catalysis, energy conversion, and
      storage. 

PMID- 25564727
TI  - A generation-time effect on the rate of molecular evolution in bacteria.
AB  - Molecular evolutionary rate varies significantly among species and a strict
      global molecular clock has been rejected across the tree of life. Generation time
      is one primary life-history trait that influences the molecular evolutionary
      rate. Theory predicts that organisms with shorter generation times evolve faster
      because of the accumulation of more DNA replication errors per unit time.
      Although the generation-time effect has been demonstrated consistently in plants
      and animals, the evidence of its existence in bacteria is lacking. The bacterial
      phylum Firmicutes offers an excellent system for testing generation-time effect
      because some of its members can enter a dormant, nonreproductive endospore state
      in response to harsh environmental conditions. It follows that spore-forming
      bacteria would--with their longer generation times--evolve more slowly than their
      nonspore-forming relatives. It is therefore surprising that a previous study
      found no generation-time effect in Firmicutes. Using a phylogenetic comparative
      approach and leveraging on a large number of Firmicutes genomes, we found
      sporulation significantly reduces the genome-wide spontaneous DNA mutation rate
      and protein evolutionary rate. Contrary to the previous study, our results
      provide strong evidence that the evolutionary rates of bacteria, like those of
      plants and animals, are influenced by generation time.

PMID- 25564729
TI  - Competitive sorption used to probe strong hydrogen bonding sites for weak organic
      acids on carbon nanotubes.
AB  - We recently proposed that weak acids (AH) adsorb to partially oxidized
      carbonaceous materials in part by forming strong hydrogen bonds with acidic
      surface groups, depicted by (A...H...O-surf)(-), known as negative charge
      assisted hydrogen bonds, (-)CAHBs. Here we use competition experiments to show
      that sorption of AH on carbon nanotubes (CNTs) can be described conceptually by a
      dual specific/nonspecific domain model, where one domain involves (-)CAHB sites
      that can become saturated. The trends observed in single-solute adsorption,
      including the stoichiometric release of hydroxide upon sorption of carboxyate or
      phenolate anions, were consistent with trends in the previous studies and pointed
      to the formation of (-)CAHB. 3,4-Dinitrophenolate formed (-)CAHBs more
      efficiently than did 2,6-dichloro-4-nitrophenolate because of alleviation of
      steric hindrance to approach by the ortho chlorines. Competition against a (
      )CAHB-capable target compound was greater when the competitor was also (-)CAHB
      capable than when it was not (e.g., benzoate as target vs 3,4-dinitrophenolate or
      nitrobenzene as competitor; mono-n-butyl phthalate as target vs methyl benzoate
      or p-tolyl acetate as competitor). Experiments also revealed competition between
      the nitroaromatic species for pi-pi electron donor-acceptor sites. The findings
      will contribute to a better understanding of the adsorption mechanism of
      ionizable compounds on carbonaceous materials.

PMID- 25564728
TI  - Specifying Associations Between Conscientiousness and Executive Functioning:
      Mental Set Shifting, Not Prepotent Response Inhibition or Working Memory
      Updating.
AB  - Conscientiousness is characterized by self-control, organization, and goal
      orientation and is positively related to a number of health and professional
      outcomes. Thus, it is commonly suggested that conscientiousness should be related
      to superior executive functioning (EF) abilities, especially prepotent response
      inhibition. However, little empirical support for this notion has emerged,
      perhaps due to oversimplified and underspecified modeling of EF. The current
      study sought to fill this gap by testing relations between conscientiousness and
      three facets of EF using a nested factors latent variable approach. Participants
      (N = 420; Mage  = 22.5; 50% male; 91% Caucasian) completed a measure of
      conscientiousness and nine EF tasks designed to tap three related yet
      distinguishable facets of EF: working memory updating, mental set shifting, and
      prepotent response inhibition. Structural equation models showed that
      conscientiousness is positively associated with the EF facet of mental set
      shifting but not response inhibition or working memory updating. Despite the
      common notion that conscientiousness is associated with cognitive abilities
      related to rigid control over impulses (i.e., inhibition), the current results
      suggest the cognitive ability most associated with conscientiousness is
      characterized by flexibility and the ability to adapt to changing environmental
      contingencies and task demands.

PMID- 25564730
TI  - Historical profiles of PCB in dated sediment cores suggest recent lake
      contamination through the "halo effect".
AB  - We investigated the major sources of polychlorinated biphenyls (PCB) and
      interpreted the environmental fate processes of these persistent organic
      pollutants in the past and current PCB contamination of three large, urbanized,
      French peri-alpine lakes. Dated sediment cores were analyzed in order to
      reconstruct and compare the historical contamination in all three lakes.
      Stratigraphic changes of PCB contents and fluxes were considered as revealing the
      temporal dynamics of PCB deposition to the lakes and the distribution of the
      seven indicator congeners (further referred to as PCBi) as an indicator of the
      main contamination origin and pathway. Although located within a single PCB
      industrial production region, concentration profiles for the three lakes differed
      in timing, peak concentration magnitudes, and in the PCBi congeners compositions.
      PCBi fluxes to the sediment and the magnitude of the temporal changes were
      generally much lower in Lake Annecy (0.05-2 ng.cm(-2).yr(-1)) as compared to
      Lakes Geneva (0.05-5 ng.cm(-2).yr(-1)) and Bourget (5-290 ng.cm(-2).yr(-1)). For
      all three lakes, the paramount contamination occurred in the early 1970s. In
      Lakes Annecy and Bourget, PCB fluxes have declined and plateaued at 0.5 and 8
      ng.cm(-2).yr(-1), respectively, since the early 1990s. In Lake Geneva, PCB fluxes
      have further decreased by the end of the XX(th) century and are now very low. For
      the most contaminated lake (Lake Bourget), the high PCBi flux (5-290 ng.cm(
      2).yr(-1)) and the predominance of heavy congeners for most of the time period
      are consistent with a huge local input to the lake. This still high rate of Lake
      Bourget is explained by transport of suspended solids from one of its affluents,
      polluted by an industrial point source. Intermediate historical levels and PCBi
      distribution over time for Lake Geneva suggest a mixed contamination (urban point
      sources and distant atmospheric transport), while atmospheric deposition to Lake
      Annecy explains its lowest contamination rate. The presently low contamination
      levels recorded in Lake Geneva correspond to atmospheric inputs, but the recent
      PCBi distribution of Lake Annecy, enriched in relatively heavy congeners, reveals
      a contamination by the neighboring Lake Bourget, following a halo effect of about
      40 km radius.

PMID- 25564732
TI  - A feedback loop between nonsense-mediated decay and the retrogene DUX4 in
      facioscapulohumeral muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is a muscular dystrophy caused by
      inefficient epigenetic repression of the D4Z4 macrosatellite array and somatic
      expression of the DUX4 retrogene. DUX4 is a double homeobox transcription factor
      that is normally expressed in the testis and causes apoptosis and FSHD when
      misexpressed in skeletal muscle. The mechanism(s) of DUX4 toxicity in muscle is
      incompletely understood. We report that DUX4-triggered proteolytic degradation of
      UPF1, a central component of the nonsense-mediated decay (NMD) machinery, is
      associated with profound NMD inhibition, resulting in global accumulation of RNAs
      normally degraded as NMD substrates. DUX4 mRNA is itself degraded by NMD, such
      that inhibition of NMD by DUX4 protein stabilizes DUX4 mRNA through a double
      negative feedback loop in FSHD muscle cells. This feedback loop illustrates an
      unexpected mode of autoregulatory behavior of a transcription factor, is
      consistent with 'bursts' of DUX4 expression in FSHD muscle, and has implications
      for FSHD pathogenesis. 

PMID- 25564735
TI  - Validation of a computer-assisted method for measurement of radiographic wear in
      total hip arthroplasty using all polyethylene cemented acetabular components.
AB  - Although cemented all polyethylene (PE) cups have been routinely used in total
      hip arthroplasty for decades, no computer-assisted method for measurement of
      radiographic wear has ever been specifically validated for these implants. Using
      a validated hip phantom model, AP plain hip radiographs were obtained
      consecutively for eight simulated wear positions. A version of Martell's Hip
      Analysis Suite software dedicated to all polyethylene sockets was used by three
      different examiners of varied experience. Bias (mean, standard deviation and 95%
      confidence interval limit), repeatability (standard deviation and 95% limit) and
      reproducibility (standard deviation and 95% limit) for two-dimensional wear
      measurements were assessed, as recommended by the current ASTM guidelines. Using
      this protocol, the dedicated software showed an overall mean bias of 0.089 +/-
      0.060 mm (mean +/- SD), and 0.118 mm for 95% CI limit. Repeatability (intra
      examiner) standard deviation and 95% limit were respectively 0.106 mm and 0.292
      mm. Reproducibility (inter examiner) standard deviation and 95% limit were
      respectively 0.112 mm and 0.308 mm. Martell Hip Analysis for all PE cemented cups
      is a reliable and low-cost instrument in the assessment of wear, despite being
      less precise than its original version dedicated to cementless components.

PMID- 25564731
TI  - A single pair of neurons links sleep to memory consolidation in Drosophila
      melanogaster.
AB  - Sleep promotes memory consolidation in humans and many other species, but the
      physiological and anatomical relationships between sleep and memory remain
      unclear. Here, we show the dorsal paired medial (DPM) neurons, which are required
      for memory consolidation in Drosophila, are sleep-promoting inhibitory neurons.
      DPMs increase sleep via release of GABA onto wake-promoting mushroom body (MB)
      alpha'/beta' neurons. Functional imaging demonstrates that DPM activation evokes
      robust increases in chloride in MB neurons, but is unable to cause detectable
      increases in calcium or cAMP. Downregulation of alpha'/beta' GABAA and GABABR3
      receptors results in sleep loss, suggesting these receptors are the sleep
      relevant targets of DPM-mediated inhibition. Regulation of sleep by neurons
      necessary for consolidation suggests that these brain processes may be
      functionally interrelated via their shared anatomy. These findings have important
      implications for the mechanistic relationship between sleep and memory
      consolidation, arguing for a significant role of inhibitory neurotransmission in
      regulating these processes. 

PMID- 25564733
TI  - Potassium dependent rescue of a myopathy with core-like structures in mouse.
AB  - Myopathies decrease muscle functionality. Mutations in ryanodine receptor 1
      (RyR1) are often associated with myopathies with microscopic core-like structures
      in the muscle fiber. In this study, we identify a mouse RyR1 model in which
      heterozygous animals display clinical and pathological hallmarks of myopathy with
      core-like structures. The RyR1 mutation decreases sensitivity to activated
      calcium release and myoplasmic calcium levels, subsequently affecting
      mitochondrial calcium and ATP production. Mutant muscle shows a persistent
      potassium leak and disrupted expression of regulators of potassium homeostasis.
      Inhibition of KATP channels or increasing interstitial potassium by diet or FDA
      approved drugs can reverse the muscle weakness, fatigue-like physiology and
      pathology. We identify regulators of potassium homeostasis as biomarkers of
      disease that may reveal therapeutic targets in human patients with myopathy of
      central core disease (CCD). Altogether, our results suggest that amelioration of
      potassium leaks through potassium homeostasis mechanisms may minimize muscle
      damage of myopathies due to certain RyR1 mutations. 

PMID- 25564736
TI  - Clinical Features of Ocular Toxocariasis in Adult Korean Patients.
AB  - PURPOSE: To investigate the clinical characteristics and treatment results of
      adult patients with ocular toxocariasis. METHODS: A total of 54 consecutive
      patients who were clinically and serologically diagnosed with ocular toxocariasis
      were retrospectively reviewed. RESULTS: Among patients, 66.7 and 77.3% showed
      increases in eosinophil cationic protein (ECP) and total Ig E in serum,
      respectively. Four eyes (7.2%) initially presented as neuroretinitis with
      subsequent motile retinal lesion. The recurrence rates in the combination
      treatment group with albendazole and corticosteroids were significantly lower
      than those in the steroid-alone group during the mean follow-up of 27.6 months (p
      = 0.001). CONCLUSIONS: The adjunctive test of serum total IgE level may be
      helpful for the diagnosis of ocular toxocariasis. Ocular toxocariasis should be
      considered in the differential diagnosis of unilateral neuroretinitis with
      subsequent motile retinal lesion. Combined treatment with albendazole and
      corticosteroids appeared to be effective for reducing the recurrence of
      intraocular inflammation.

PMID- 25564734
TI  - TBX6 null variants and a common hypomorphic allele in congenital scoliosis.
AB  - BACKGROUND: Congenital scoliosis is a common type of vertebral malformation.
      Genetic susceptibility has been implicated in congenital scoliosis. METHODS: We
      evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han
      Chinese controls, and 2 pedigrees, family members of which had a 16p11.2
      deletion, using comparative genomic hybridization, quantitative polymerase-chain
      reaction analysis, and DNA sequencing. We carried out tests of replication using
      an additional series of 76 Han Chinese persons with congenital scoliosis and a
      multicenter series of 42 persons with 16p11.2 deletions. RESULTS: We identified a
      total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic
      congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166
      controls (P<3.8*10(-6)). These null alleles include copy-number variants (12
      instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1
      nonsense and 4 frame-shift mutations). However, the discordant intrafamilial
      phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null
      mutation is insufficient to cause congenital scoliosis. We went on to identify a
      common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null
      mutations (P<1.1*10(-6)). Replication studies involving additional persons with
      congenital scoliosis who carried a deletion affecting TBX6 confirmed this
      compound inheritance model. In vitro functional assays suggested that the risk
      haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6
      associated congenital scoliosis. CONCLUSIONS: Compound inheritance of a rare null
      mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital
      scoliosis cases in the series that we analyzed. (Funded by the National Basic
      Research Program of China and others.).

PMID- 25564739
TI  - Real-time prescription drug monitoring program in Australia: We should be ready.

PMID- 25564737
TI  - The endothermic ATP hydrolysis and crossbridge attachment steps drive the
      increase of force with temperature in isometric and shortening muscle.
AB  - The isometric tetanic tension of skeletal muscle increases with temperature
      because attached crossbridge states bearing a relatively low force convert to
      those bearing a higher force. It was previously proposed that the tension
      generating step(s) in the crossbridge cycle was highly endothermic and was
      therefore itself directly targeted by changes in temperature. However, this did
      not explain why a rapid rise in temperature (a temperature jump) caused a much
      slower rate of rise of tension than a rapid length step. This led to suggestions
      that the step targeted by a temperature rise is not the tension-generating step
      but is an extra step in the attached pathway of the crossbridge cycle, perhaps
      located on a parallel pathway. This enigma has been a major obstacle to a full
      understanding of the operation of the crossbridge cycle. We have now used a
      previously developed mechano-kinetic model of the crossbridge cycle in frog
      muscle to simulate the temperature dependence of isometric tension and shortening
      velocity. We allowed all five steps in the cycle to be temperature-sensitive.
      Models with different starting combinations of enthalpy changes and activation
      enthalpies for the five steps were refined by downhill simplex runs and scored by
      their ability to fit experimental data on the temperature dependence of isometric
      tension and the relationship between force and shortening velocity in frog
      muscle. We conclude that the first tension-generating step may be weakly
      endothermic and that the rise of tension with temperature is largely driven by
      the preceding two strongly endothermic steps of ATP hydrolysis and attachment of
      M.ADP.Pi to actin. The refined model gave a reasonable fit to the available
      experimental data and after a temperature jump the overall rate of tension rise
      was much slower than after a length step as observed experimentally. The findings
      aid our understanding of the crossbridge cycle by showing that it may not be
      necessary to include an additional temperature-sensitive step.

PMID- 25564738
TI  - Cry1Ab protein from Bacillus thuringiensis and MON810 cry1Ab-transgenic maize
      exerts no adjuvant effect after airway exposure.
AB  - The genetically modified (GM) maize event MON810 has been inserted with a
      processed version of the transgene, cry1Ab, derived from the soil bacterium
      Bacillus thuringiensis (Bt) to express proteins with insecticidal properties.
      Such proteins may introduce new allergens and also act as adjuvants that promote
      allergic responses. While focus has been on safe consumption and hence the oral
      exposure to GM food and feed, little is known regarding inhalation of pollen and
      desiccated airborne plant material from GM crops. The aim of this study was to
      investigate whether plant material from the Cry1Ab-expressing maize variety
      MON810, or trypsin-activated Cry1Ab (trypCry1Ab) protein produced in recombinant
      bacteria, may act as adjuvants against the allergen ovalbumin (OVA) in a mouse
      model of airway allergy. A clear proallergic adjuvant effect of the mucosal
      adjuvant cholera toxin (CT) was demonstrated, determined as increased specific
      IgE, eosinophils and Th2 cytokines in MLN cell supernates, while no elevation in
      OVA-specific antibodies or cytokine release from MLN cells after stimulation with
      OVA were observed in mice receiving Cry1Ab-containing plant materials or the
      trypCry1Ab protein. Our data suggest that Cry1Ab proteins had no detectable
      systemic adjuvant effect in mice after airway exposure. Further experiments with
      purified plant proteins, as well as long-term exposures needs be conducted to
      further evaluate exposures experienced in real-life situations. 

PMID- 25564740
TI  - Breaking good: a chemist wanders into entomology.
AB  - In this highly personal account of my career in science, I try to show how many
      others influenced its course. I was able to abandon work in pure chemistry and
      microbiology and to take up research in entomology only with the help of others.
      My faith in the value of collaborative, interdisciplinary work has been the key
      to success. Our focus on proteins of insect hemolymph has provided valuable
      insights into insect biochemistry and physiology. 

PMID- 25564741
TI  - Extrafloral nectar at the plant-insect interface: a spotlight on chemical
      ecology, phenotypic plasticity, and food webs.
AB  - Plants secrete extrafloral nectar (EFN) as an induced defense against herbivores.
      EFN contains not only carbohydrates and amino acids but also pathogenesis-related
      proteins and other protective enzymes, making EFN an exclusive reward. EFN
      secretion is commonly induced after wounding, likely owing to a jasmonic acid
      induced cell wall invertase, and is limited by phloem sucrose availability: Both
      factors control EFN secretion according to the optimal defense hypothesis. Non
      ant EFN consumers include parasitoids, wasps, spiders, mites, bugs, and predatory
      beetles. Little is known about the relevance of EFN to the nutrition of its
      consumers and, hence, to the structuring of arthropod communities. The mutualism
      can be established quickly among noncoevolved (e.g., invasive) species,
      indicating its easy assembly is due to ecological fitting. Therefore, increasing
      efforts are directed toward using EFN in biocontrol. However, documentation of
      the importance of EFN for the communities of plants and arthropods in natural,
      invasive, and agricultural ecosystems is still limited. 

PMID- 25564742
TI  - Mirid (Hemiptera: Heteroptera) specialists of sticky plants: adaptations,
      interactions, and ecological implications.
AB  - Sticky plants-those having glandular trichomes (hairs) that produce adhesive,
      viscous exudates-can impede the movement of, and entrap, generalist insects.
      Disparate arthropod groups have adapted to these widespread and taxonomically
      diverse plants, yet their interactions with glandular hosts rarely are
      incorporated into broad ecological theory. Ecologists and entomologists might be
      unaware of even well-documented examples of insects that are sticky-plant
      specialists. The hemipteran family Miridae (more specifically, the omnivorous
      Dicyphini: Dicyphina) is the best-known group of arthropods that specializes on
      sticky plants. In the first synthesis of relationships with glandular plants for
      any insect family, we review mirid interactions with sticky hosts, including
      their adaptations (behavioral, morphological, and physiological) and mutualisms
      with carnivorous plants, and the ecological and agricultural implications of
      mirid-sticky plant systems. We propose that mirid research applies generally to
      tritrophic interactions on trichome-defended plants, enhances an understanding of
      insect-plant interactions, and provides information useful in managing crop
      pests. 

PMID- 25564743
TI  - Physiology of environmental adaptations and resource acquisition in cockroaches.
AB  - Cockroaches are a group of insects that evolved early in geological time. Because
      of their antiquity, they for the most part display generalized behavior and
      physiology and accordingly have frequently been used as model insects to examine
      physiological and biochemical mechanisms involved with water balance, nutrition,
      reproduction, genetics, and insecticide resistance. As a result, a considerable
      amount of information on these topics is available. However, there is much more
      to be learned by employing new protocols, microchemical analytical techniques,
      and molecular biology tools to explore many unanswered questions. 

PMID- 25564744
TI  - Root-feeding insects and their interactions with organisms in the rhizosphere.
AB  - Root-feeding insects are an increasingly studied group of herbivores whose
      impacts on plant productivity and ecosystem processes are widely recognized.
      Their belowground habitat has hitherto hindered our understanding of how they
      interact with other organisms that share the rhizosphere. A surge in research in
      this area has now shed light on these interactions. We review key interactions
      between root-feeding insects and other rhizospheric organisms, including
      beneficial plant microbes (mycorrhizal fungi, nitrogen-fixing bacteria),
      antagonists/pathogens of root herbivores (arthropod predators, entomopathogenic
      nematodes/fungi, and bacterial pathogens), competitors, symbiotic microbes, and
      detritivores. Patterns for these interactions are emerging. The negative impacts
      of mycorrhizal fungi on root herbivores, for instance, raise the intriguing
      prospect that these fungi could be used for pest management. Moreover, a better
      understanding of symbiotic microbes in root herbivores, especially those
      underpinning digestion, could prove useful in industries such as biofuel
      production. 

PMID- 25564745
TI  - Insecticide resistance in mosquitoes: impact, mechanisms, and research
      directions.
AB  - Mosquito-borne diseases, the most well known of which is malaria, are among the
      leading causes of human deaths worldwide. Vector control is a very important part
      of the global strategy for management of mosquito-associated diseases, and
      insecticide application is the most important component in this effort. However,
      mosquito-borne diseases are now resurgent, largely because of the insecticide
      resistance that has developed in mosquito vectors and the drug resistance of
      pathogens. A large number of studies have shown that multiple, complex resistance
      mechanisms-in particular, increased metabolic detoxification of insecticides and
      decreased sensitivity of the target proteins-or genes are likely responsible for
      insecticide resistance. Gene overexpression and amplification, and mutations in
      protein-coding-gene regions, have frequently been implicated as well. However, no
      comprehensive understanding of the resistance mechanisms or regulation involved
      has yet been developed. This article reviews current knowledge of the molecular
      mechanisms, genes, gene interactions, and gene regulation governing the
      development of insecticide resistance in mosquitoes and discusses the potential
      impact of the latest research findings on the basic and practical aspects of
      mosquito resistance research. 

PMID- 25564746
TI  - Vector ecology of equine piroplasmosis.
AB  - Equine piroplasmosis is a disease of Equidae, including horses, donkeys, mules,
      and zebras, caused by either of two protozoan parasites, Theileria equi or
      Babesia caballi. These parasites are biologically transmitted between hosts via
      tick vectors, and although they have inherent differences they are categorized
      together because they cause similar pathology and have similar morphologies, life
      cycles, and vector relationships. To complete their life cycle, these parasites
      must undergo a complex series of developmental events, including sexual-stage
      development in their tick vectors. Consequently, ticks are the definitive hosts
      as well as vectors for these parasites, and the vector relationship is restricted
      to a few competent tick species. Because the vector relationship is critical to
      the epidemiology of these parasites, we highlight current knowledge of the vector
      ecology of these tick-borne equine pathogens, emphasizing tick transmissibility
      and potential control strategies to prevent their spread. 

PMID- 25564747
TI  - Soft skills matter.

PMID- 25564748
TI  - Hostile sexism (de)motivates women's social competition intentions: The
      contradictory role of emotions.
AB  - In the present research, we examine the ways in which exposure to hostile sexism
      influences women's competitive collective action intentions. Prior to testing our
      main model, our first study experimentally induced high versus low levels of
      security-comfort with the aim of providing experimental evidence for the proposed
      causal link between these emotions and intentions to engage in social
      competition. Results showed that lower levels of security-comfort reduced women's
      readiness to compete socially with men. Experiment 2 investigated the effect of
      hostile sexism on women's emotional reactions and readiness to engage in social
      competition. Consistent with the proposed model, results showed that exposure to
      hostile beliefs about women (1) increased anger-frustration and (2) decreased
      security-comfort. More specifically, exposure to hostile sexism had a positive
      indirect effect on social competition intentions through anger-frustration, and a
      negative indirect effect through security-comfort. 

PMID- 25564749
TI  - The training of a trauma therapist: bringing it home.

PMID- 25564753
TI  - Radiographer-led plan selection for bladder cancer radiotherapy: initiating a
      training programme and maintaining competency.
AB  - OBJECTIVE: The implementation of plan of the day selection for patients receiving
      radiotherapy (RT) for bladder cancer requires efficient and confident decision
      making. This article describes the development of a training programme and
      maintenance of competency. METHODS: Cone beam CT (CBCT) images acquired on
      patients receiving RT for bladder cancer were assessed to establish baseline
      competency and training needs. A training programme was implemented, and
      observers were asked to select planning target volumes (PTVs) on two groups of 20
      patients' images. After clinical implementation, the PTVs chosen were reviewed
      offline, and an audit performed after 3 years. RESULTS: A mean of 73% (range, 53
      93%) concordance rate was achieved prior to training. Subsequent to training, the
      mean score decreased to 66% (Round 1), then increased to 76% (Round 2). Six
      radiographers and two clinicians successfully completed the training programme.
      An independent observer reviewed the images offline after clinical
      implementation, and a 91% (126/139) concordance rate was achieved. During the
      audit, 125 CBCT images from 13 patients were reviewed by a single observer and
      concordance was 92%. CONCLUSION: Radiographer-led selection of plan of the day
      was implemented successfully with the use of a training programme and continual
      assessment. Quality has been maintained over a period of 3 years. ADVANCES IN
      KNOWLEDGE: The training programme was successful in achieving and maintaining
      competency for a plan of the day technique.

PMID- 25564754
TI  - Direct asymmetric dearomatization of 2-naphthols by scandium-catalyzed
      electrophilic amination.
AB  - Catalytic asymmetric aminative dearomatization of 1-substituted 2-naphthols was
      successfully implemented with electrophilic azodicarboxylates under the catalysis
      of chiral Sc(III)/pybox complexes. This intermolecular reaction represents a
      hitherto unknown enantioselective C-N bond-forming process through direct
      dearomatization of phenolic compounds to generate chiral nitrogen-containing
      quaternary carbon stereocenters.

PMID- 25564756
TI  - Naturally occurring, resistance-associated hepatitis C virus NS5A variants are
      linked to interleukin-28B genotype and are sensitive to interferon-based therapy.
AB  - AIM: The presence of resistance-associated variants (RAV) may attenuate the
      efficacy of direct-acting antivirals (DAA) in combination therapy for hepatitis
      C. The aim of this study was to characterize the NS3 and NS5A regions of
      hepatitis C virus (HCV) in naturally occurring RAV. METHODS: The NS3 and NS5A
      regions of HCV were amplified by nested polymerase chain reaction and their
      nucleotide sequences were determined by direct sequencing in 493 genotype 1b
      patients naive to DAA-based therapies. The effect of baseline RAV on response to
      pegylated interferon and ribavirin therapy was analyzed in 65 patients after
      stratification by interleukin (IL)-28B genotype. RESULTS: The incidence of RAV
      was 7.9% in NS3 (V36I/L, 1.2%; T54S, 2.8%; Q80K/R, 3.0%; A156S, 0.2%; and
      D168E/T, 2.4%) and 20.2% in NS5A (L31I/M, 2.2%; and Y93H, 19.0%). The incidence
      in interferon experienced and naive patients was similar. The incidence of Y93H
      in NS5A was significantly higher in the IL-28B TT genotype (rs8099917) than non
      TT (27.1% vs 9.5%, P < 0.001). The virological response to pegylated interferon
      plus ribavirin therapy was not affected by the presence of RAV in IL-28B TT
      genotype. CONCLUSION: RAV, especially Y93H in the NS5A region, were highly
      prevalent in DAA naive patients with genotype 1b HCV in Japan and were linked to
      IL-28B TT genotype. Interferon-based therapy could be an alternative for patients
      with RAV because these variants did not attenuate the response to that therapy.
      The analysis of RAV may impact the selection of the optimal treatment strategy.

PMID- 25564755
TI  - Cardiac Calcifications in Adults with Congenital Heart Defects.
AB  - OBJECTIVE: We investigated the type and extent of calcification in a series of
      heart specimens from adult congenital heart disease patients because recent
      autopsy observations suggested a high prevalence of calcification. DESIGN: We
      used computed tomography to examine seven heart specimens from adults (>18 years
      old) with a congenital heart defect collected with permission from the family
      during a recent 3-year period. Clinical data regarding diagnosis, history, and
      imaging studies were recorded. The 3D data sets were reviewed after reformatting
      as maximum intensity projection and volumetric renderings to determine the
      pattern and extent of calcium deposition. RESULTS: Five of the seven hearts had
      extensive calcifications in one or more of three patterns: atherosclerosis
      associated in the three oldest cases; surgery associated in four of five hearts
      that had undergone heart surgery; and myocardial calcification remote from
      surgical sites in two cases. Myocardial calcification was associated with
      regional dysfunction and was present in the three patients that died suddenly and
      unexpectedly. CONCLUSION: Cardiac calcification was frequent in our series of
      heart specimens from adults with congenital heart defects, was often but not
      uniformly associated with prior surgery, and, in our small series, was associated
      with regional dysfunction and sudden death.

PMID- 25564757
TI  - Findings of a Naloxone Database and its Utilization to Improve Safety and
      Education in a Tertiary Care Medical Center.
AB  - INTRODUCTION: Analyzing hospital naloxone use may assist in identification of
      areas for quality and safety improvement. Our primary objective is to quantitate
      the incidence of hospital naloxone use and to assess certain patient populations
      at risk. METHODS: During the years 2008 to 2011, each clinical scenario where
      naloxone was administered on an in-patient care ward was reviewed. The events
      were assessed to separate situations where naloxone rescue was effective in
      reversing opioid-induced intoxication vs. others. Further analysis was conducted
      to stratify patient populations at greatest risk. RESULTS: Naloxone was
      administered for well-defined opioid-induced respiratory depression and
      oversedation 61% of the time, the remainder used for patient deterioration of
      other etiology. Surgical populations are at risk with an incidence of 3.8/1,000
      hospitalized patients, and this is the greatest within 24 hours of surgery.
      General surgical patients represent the highest surgical patient risk at
      5.5/1,000. Medical patients represent lower risk at 2.0/1,000. Patients with
      patient-controlled analgesia and epidural opioid infusion are high risk at 12.1
      and 13.1/1,000 patients, respectively. Many quality and safety interventions were
      gradually implemented in response to this data and are summarized. These include
      nursing and provider education, electronic medical record modification, and more
      stringent patient monitoring practices. CONCLUSION: Examination of naloxone use
      can assist in the identification and stratification of patients at risk for
      opioid-induced respiratory depression and oversedation and can serve as a driver
      for improvements in hospital patient safety. This information can also guide
      other institutions interested in similar improvements.

PMID- 25564758
TI  - Training students in serologic reaction grading increased perceptions of self
      efficacy and ability to recognize serologic reactions but decreased grading
      accuracy.
AB  - BACKGROUND: The ability to recognize and grade serologic reactions in manual
      techniques remains an important skill both for reference laboratories and in
      disaster-relocated laboratory services. Developing skills in recognizing and
      grading serologic reactions is limited to some extent by the range of samples
      available. STUDY DESIGN AND METHODS: Twenty-six students studying transfusion
      science were presented with blinded grading panels consisting of mixes of natural
      cells and kodecytes (natural cells modified with synthetic blood group antigens)
      representing a range of serologic grades. Results from 15-minute exercises over
      17 contact weeks were assessed to determine if training with grading panels would
      have an impact on the ability of students to recognize and correctly grade
      serologic reactions. Twenty-one clinically active practitioners also took part in
      a single analysis. RESULTS: Grading exercises found that the use of kodecytes and
      natural negative cells were able to identify deficiencies in both students' and
      practitioners' ability to recognize negative and grade serologic reactions. The
      seventeen 15-minute exercises undertaken with students revealed that although
      there was some improvement in performance in recognizing positive and negative
      serologic reactions there was also a degradation in ability to accurately grade.
      Self-assessment showed a major improvement in students' self-efficacy.
      CONCLUSIONS: The use of serologic grading panels created with kodecytes was
      suitable as a tool to recognize and monitor serologic grading abilities. Evidence
      suggests that for both students and practitioners to gain and sustain competency
      in serologic reaction recognition and grading, they will require ongoing training
      and monitoring of competence.

PMID- 25564759
TI  - Plasmon enhancement effect in Au gold nanorods@Cu2O core-shell nanostructures and
      their use in probing defect states.
AB  - Au@Cu2O core-shell nanostructures are fabricated to have a plasmon enhancement
      effect using Au nanorods (Au NRs) as a plasmon-tailorable core. By varying the
      concentration of Au NRs, we can tune the shell thickness in the range of 10-25
      nm. The shell is composed of Cu2O nanocrystallites. Because of the thin shells,
      the extinction spectra at wavelength >500 nm are dominated by the Au core.
      However, the large dielectric constant of the shell causes an obvious red shift
      of the surface plasmon resonance (SPR) band of the Au nanorod. Besides,
      transverse octupolar SPR appears as a result of the anisotropy of the core and
      the high dielectric constant of the shell. The anisotropic geometry of the Au NR
      is found to support the octupolar resonances at smaller sizes than for their
      spherical counterpart. Theoretical simulations indicate that the transverse SPR
      bands are divided into two resonances, which are dipolar- and octupolar-dominant,
      respectively. The Cu2O shell degrades via a defect-mediated oxidative pathway,
      which is aggravated upon longitudinal SPR excitation. The SPR-mediated local
      field enhancement and resonance energy transfer are found to enhance the
      excitation of the defect states in the shell, thus providing a simple yet
      selective probing strategy for defect states. 

PMID- 25564760
TI  - A surface hopping algorithm for nonadiabatic minimum energy path calculations.
AB  - The article introduces a robust algorithm for the computation of minimum energy
      paths transiting along regions of near-to or degeneracy of adiabatic states. The
      method facilitates studies of excited state reactivity involving weakly avoided
      crossings and conical intersections. Based on the analysis of the change in the
      multiconfigurational wave function the algorithm takes the decision whether the
      optimization should continue following the same electronic state or switch to a
      different state. This algorithm helps to overcome convergence difficulties near
      degeneracies. The implementation in the MOLCAS quantum chemistry package is
      discussed. To demonstrate the utility of the proposed procedure four examples of
      application are provided: thymine, asulam, 1,2-dioxetane, and a three-double-bond
      model of the 11-cis-retinal protonated Schiff base.

PMID- 25564761
TI  - Long-term outcomes after hospitalization with spontaneous bacterial peritonitis.
AB  - OBJECTIVE: To assess the determinants of long-term outcome in patients with
      spontaneous bacterial peritonitis (SBP). METHODS: This study was conducted
      retrospectively. Kaplan-Meier (KM) and Cox proportional hazards survival analyses
      were performed. RESULTS: Altogether, 93 patients with SBP were identified, with
      their mean age of 57.9 +/- 12.9 years, Child-Pugh score 10.4 +/- 1.9 and model
      for end-stage liver disease (MELD) score 20.2 +/- 6.8. The etiology of chronic
      liver disease (CLD) was alcohol-related liver disease (ARLD) (n = 58) and viral
      hepatitis/non-alcoholic steatohepatitis (n = 28). SBP was the index presentation
      of cirrhosis in 26 (28.0%) patients. Overall mortality was 80.6%; among them
      81.3% were liver-related, and 33 (35.5%) died during index hospitalization. In
      total, 70.0% of patients who survived index hospitalization died during follow
      up, with a median survival of 12.5 months. Estimated survival at 3 months, 1 year
      and 5 years was 54.8%, 34.4% and 15.2%, respectively. Non-ARLD etiology for CLD
      was an independent predictor of overall mortality (HR 3.484, 95% CI 1.802-6.757,
      P < 0.001) and mortality in those surviving hospitalization (HR 2.319, 95% CI
      1.210-4.444, P = 0.011). Hepatorenal syndrome did not predict outcomes. Two
      (3.3%) patients surviving hospitalization underwent liver transplantation (LT).
      CONCLUSIONS: One-year survival after hospitalization with SBP remains poor
      (34.4%) with unacceptably low LT rates. Non-ARLD etiology for CLD is an
      independent predictor of both overall mortality and mortality after discharge. In
      view of the projected increase in non-alcoholic steatohepatitis-related CLD,
      screening strategies for timely CLD diagnosis are warranted.

PMID- 25564764
TI  - Large resistivity modulation in mixed-phase metallic systems.
AB  - In numerous systems, giant physical responses have been discovered when two
      phases coexist; for example, near a phase transition. An intermetallic FeRh
      system undergoes a first-order antiferromagnetic to ferromagnetic transition
      above room temperature and shows two-phase coexistence near the transition. Here
      we have investigated the effect of an electric field to FeRh/PMN-PT
      heterostructures and report 8% change in the electrical resistivity of FeRh
      films. Such a 'giant' electroresistance (GER) response is striking in metallic
      systems, in which external electric fields are screened, and thus only weakly
      influence the carrier concentrations and mobilities. We show that our FeRh films
      comprise coexisting ferromagnetic and antiferromagnetic phases with different
      resistivities and the origin of the GER effect is the strain-mediated change in
      their relative proportions. The observed behaviour is reminiscent of colossal
      magnetoresistance in perovskite manganites and illustrates the role of mixed
      phase coexistence in achieving large changes in physical properties with low
      energy external perturbation. 

PMID- 25564763
TI  - Stochastic modeling indicates that aging and somatic evolution in the
      hematopoetic system are driven by non-cell-autonomous processes.
AB  - Age-dependent tissue decline and increased cancer incidence are widely accepted
      to be rate-limited by the accumulation of somatic mutations over time. Current
      models of carcinogenesis are dominated by the assumption that oncogenic mutations
      have defined advantageous fitness effects on recipient stem and progenitor cells,
      promoting and rate-limiting somatic evolution. However, this assumption is
      markedly discrepant with evolutionary theory, whereby fitness is a dynamic
      property of a phenotype imposed upon and widely modulated by environment. We
      computationally modeled dynamic microenvironment-dependent fitness alterations in
      hematopoietic stem cells (HSC) within the Sprengel-Liebig system known to govern
      evolution at the population level. Our model for the first time integrates real
      data on age-dependent dynamics of HSC division rates, pool size, and accumulation
      of genetic changes and demonstrates that somatic evolution is not rate-limited by
      the occurrence of mutations, but instead results from aged microenvironment
      driven alterations in the selective/fitness value of previously accumulated
      genetic changes. Our results are also consistent with evolutionary models of
      aging and thus oppose both somatic mutation-centric paradigms of carcinogenesis
      and tissue functional decline. In total, we demonstrate that aging directly
      promotes HSC fitness decline and somatic evolution via non-cell-autonomous
      mechanisms.

PMID- 25564765
TI  - Novel, high-definition 3-D endoscopy system with real-time compression
      communication system to aid diagnoses and treatment between hospitals in
      Thailand.
AB  - INTRODUCTION: Traditionally, laparoscopy has been based on 2-D imaging, which
      represents a considerable challenge. As a result, 3-D visualization technology
      has been proposed as a way to better facilitate laparoscopy. We compared the
      latest 3-D systems with high-end 2-D monitors to validate the usefulness of new
      systems for endoscopic diagnoses and treatment in Thailand. METHODS: We compared
      the abilities of our high-definition 3-D endoscopy system with real-time
      compression communication system with a conventional high-definition (2-D)
      endoscopy system by asking health-care staff to complete tasks. Participants
      answered questionnaires and whether procedures were easier using our system or
      the 2-D endoscopy system. RESULTS: Participants were significantly faster at
      suture insertion with our system (34.44 +/- 15.91 s) than with the 2-D system
      (52.56 +/- 37.51 s) (P < 0.01). Most surgeons thought that the 3-D system was
      good in terms of contrast, brightness, perception of the anteroposterior position
      of the needle, needle grasping, inserting the needle as planned, and needle
      adjustment during laparoscopic surgery. Several surgeons highlighted the
      usefulness of exposing and clipping the bile duct and gallbladder artery, as well
      as dissection from the liver bed during laparoscopic surgery. In an image
      transfer experiment with RePure-L(r), participants at Rajavithi Hospital could
      obtain reconstructed 3-D images that were non-inferior to conventional images
      from Chulalongkorn University Hospital (10 km away). CONCLUSION: These data
      suggest that our newly developed system could be of considerable benefit to the
      health-care system in Thailand. Transmission of moving endoscopic images from a
      center of excellence to a rural hospital could help in the diagnosis and
      treatment of various diseases.

PMID- 25564766
TI  - Comparison of prevalence of inadequate nutrient intake based on body weight
      status of adults in the United States: an analysis of NHANES 2001-2008.
AB  - OBJECTIVE: To compare micronutrient intake status of those overweight and those
      obese with normal weight adults. METHODS: Using total nutrient intake (from foods
      and supplements) from the National Health and Nutrition Examination Survey
      (NHANES) 2001-2008, we determined usual intakes for micronutrients using the
      National Cancer Institute methodology in adults (n = 18,177). Only subjects with
      reliable dietary records were included and pregnant and lactating females were
      excluded. Subjects were categorized by body weight status as either normal weight
      (body mass index [BMI] < 25), overweight (BMI >= 25 to < 30), or obese (BMI >=
      30). RESULTS: A substantial proportion of the adult population (over 40%) had
      inadequate intakes of vitamin A, vitamin C, vitamin D, vitamin E, calcium, and
      magnesium. Compared to normal weight adults, obese adults had about 5% to 12%
      lower (p < 0.05) intakes of micronutrients and higher (p < 0.01) prevalence of
      nutrient inadequacy. CONCLUSION: We conclude that obese adults compared to normal
      weight adults have lower micronutrient intake and higher prevalence of
      micronutrient inadequacy.

PMID- 25564762
TI  - A lysine-rich motif in the phosphatidylserine receptor PSR-1 mediates recognition
      and removal of apoptotic cells.
AB  - The conserved phosphatidylserine receptor (PSR) was first identified as a
      receptor for phosphatidylserine, an 'eat-me' signal exposed by apoptotic cells.
      However, several studies suggest that PSR may also act as an arginine
      demethylase, a lysyl hydroxylase, or an RNA-binding protein through its N
      terminal JmjC domain. How PSR might execute drastically different biochemical
      activities, and whether they are physiologically significant, remain unclear.
      Here we report that a lysine-rich motif in the extracellular domain of PSR-1, the
      Caenorhabditis elegans PSR, mediates specific phosphatidylserine binding in vitro
      and clearance of apoptotic cells in vivo. This motif also mediates
      phosphatidylserine-induced oligomerization of PSR-1, suggesting a mechanism by
      which PSR-1 activates phagocytosis. Mutations in the phosphatidylserine-binding
      motif, but not in its Fe(II) binding site critical for the JmjC activity, abolish
      PSR-1 phagocytic function. Moreover, PSR-1 enriches and clusters around apoptotic
      cells during apoptosis. These results establish that PSR-1 is a conserved,
      phosphatidylserine-recognizing phagocyte receptor. 

PMID- 25564767
TI  - Facile synthesis of ultra-small PbSe nanorods for photovoltaic application.
AB  - Nanocrystal array solar cells based on lead chalcogenide quantum dots (QDs) have
      recently achieved a high power conversion efficiency of over 8%. The device
      performance is expected to further increase by using 1-dimensional nanorods
      (NRs), due to their improved carrier transport over zero-dimensional quantum
      dots. However, previously reported PbSe NRs have not been used in solar cells
      mainly because of their large diameters, resulting in a small bandgap unsuitable
      for photovoltaic application. In this work, we have demonstrated a new method for
      synthesizing monodisperse ultra-small PbSe NRs with the diameter approaching 2 nm
      (Eg > 1.2 eV), which can be attributed to the use of diphenylphosphine (DPP) and
      trans-2-octenoic acid (t-2-OA). The introduction of trace DPP can greatly lower
      the reaction temperature, leading to reduced diameters for the obtained PbSe NRs
      as well as largely increased yield. The use of short-chain t-2-OA together with
      oleic acid as capping ligands results in high monomer reactivity, fast nucleus
      diffusion and high growth rate, which realize the anisotropic growth of ultra
      small PbSe NRs at low reaction temperatures. The PbSe NRs show n-type properties
      and high electron mobility as measured using field-effect transistors. The PbSe
      NRs with narrow diameters also demonstrate a suitable bandgap for photovoltaic
      application. They are used for the first time in solar cells and their improved
      efficiency is demonstrated when used together with QDs. 

PMID- 25564768
TI  - Occupational diseases in individuals exposed to metal working fluids.
AB  - PURPOSE OF REVIEW: To examine the current occurrence of respiratory and skin
      disease in workers who do metal machining with metal working fluids (MWFs), a
      common work process in manufacturing. RECENT FINDINGS: A summary of the 27
      recognized outbreaks of respiratory disease in workers exposed to MWFs was
      published. New studies have identified irritative symptoms among workers with low
      level exposures. There were review articles discussing the content, measurement
      and control of microbial agents in MWFs. SUMMARY: The occurrence of work-related
      asthma and hypersensitivity pneumonitis appears to have diminished in the last 10
      years. This is presumed to be secondary to lower air levels from the use of newer
      machining equipment, which are enclosed and have local ventilation as well as
      better control of microbial contaminants. However, clinicians need to be aware
      that at the minimum irritative symptoms of the upper respiratory tract are still
      being reported at these lower exposure levels and there remains the possibility
      of the development of asthma and hypersensitivity pneumonitis. Given the
      widespread use of MWFs in manufacturing facilities, clinicians need to consider
      the possibility that MWFs are the cause or are aggravating the respiratory and
      dermatologic conditions of their patients.

PMID- 25564769
TI  - Relative toxicity of bifenthrin to Hyalella azteca in 10 day versus 28 day
      exposures.
AB  - Many watersheds in the Central Valley region of California are listed as impaired
      due to pyrethroid-associated sediment toxicity. The Central Valley Regional Water
      Quality Control Board is developing numeric sediment quality criteria for
      pyrethroids, beginning with bifenthrin. Criteria are being developed using
      existing data, along with data from 10 d and 28 d toxicity tests with Hyalella
      azteca conducted as part of the current study. A single range-finder and 2
      definitive tests were conducted for each test duration. Median lethal
      concentrations (LC50s), as well as LC20s and inhibition concentrations (IC20s)
      were calculated based on measured whole sediment bifenthrin concentrations and
      interstitial water concentrations. Sediment LC50s were also corrected for organic
      C content. Average LC50s were not significantly different in 10 d versus 28 d
      tests with H. azteca: 9.1 and 9.6 ng/g bifenthrin for 10 d and 28 d tests,
      respectively. Average LC20 values were also similar with concentrations at 7.1
      and 7.0 for 10 d and 28 d tests, respectively. Bifenthrin inhibition
      concentrations (IC20s) based on amphipod growth were variable, particularly in
      the 28 d tests, where a clear dose-response relationship was observed in only 1
      of the definitive experiments. Average amphipod growth IC20s were 3.9 and 9.0
      ng/g for 10 d and 28 d tests, respectively. Amphipod growth calculated as biomass
      resulted in IC20s of 4.1 and 6.3 ng/g for the 10 d and 28 d tests, respectively.
      Lack of a clear growth effect in the longer term test may be related to the lack
      of food adjustment to account for amphipod mortality in whole sediment exposures.
      The average C-corrected LC50s were 1.03 and 1.09 MUg/g OC for the 10 d and 28 d
      tests, respectively. Interstitial water LC50s were determined as the measured
      dissolved concentration of bifenthrin relative to interstitial water dissolved
      organic carbon. The average LC50s for dissolved interstitial water bifenthrin
      were 4.23 and 4.28 ng/L for the 10 d and 28 d tests, respectively. In addition, a
      set of 10 d and 28 d tests were conducted at 15  degrees C to assess the relative
      toxicity of bifenthrin at a lower temperature than the standard 23  degrees C
      test temperature. These results showed that bifenthrin was more toxic at the
      lower temperature, with LC50s of 5.1 and 3.4 ng/g bifenthrin in 10 d and 28 d
      tests, respectively. Amphipod growth at 15  degrees C after a 28 d exposure
      resulted in the lowest effect concentration of all experiments conducted (IC20 =
      0.61 ng/g). This article discusses how bifenthrin dose-response data from 10 d
      and 28 d exposures inform development of sediment quality criteria for this
      pesticide for California Central Valley watersheds.

PMID- 25564770
TI  - Metoclopramide for post-pyloric placement of naso-enteral feeding tubes.
AB  - BACKGROUND: Enteral nutrition by feeding tube is a common and efficient method of
      providing nutritional support to prevent malnutrition in hospitalised patients
      who have adequate gastrointestinal function but who are unable to eat. Gastric
      feeding may be associated with higher rates of food aspiration and pneumonia than
      post-pyloric naso-enteral tubes. Thus, enteral feeding tubes are placed directly
      into the small intestine rather than the stomach, and the use of metoclopramide,
      a prokinetic agent, has been recommended to achieve post-pyloric placement, but
      its efficacy is controversial. Moreover, metoclopramide may include adverse
      reactions, which with high doses or prolonged use may be serious and
      irreversible. OBJECTIVES: To determine the effect of intravenous metoclopramide
      on post-pyloric placement of the naso-enteral tube in adults. SEARCH METHODS:
      Trials were identified by searching the Cochrane Central Register of Controlled
      Trials (CENTRAL; 2014, Issue 10) which includes the CUGPD group's specialised
      register of trials, MEDLINE (1996 to 21 October 2014), EMBASE (1988 to 21 October
      2014), LILACS (2005 to 21 October 2014)   We did not confine our search to
      English language publications. Searches in all databases were updated originally
      in January 2005, then in November 2008 and again in October 2014. No new studies
      were found in 2008 or in 2014. SELECTION CRITERIA: We selected randomised
      controlled trials of adults needing enteral nutrition, who received intravenous
      or intramuscular metoclopramide to aid placement of transpyloric naso-enteral
      feeding tubes, compared to placebo or no intervention. DATA COLLECTION AND
      ANALYSIS: We used standard methodological procedures expected by The Cochrane
      Collaboration. All analyses were performed according to the intention-to-treat
      method. We present risk ratios (RR) with 95% confidence intervals (CI). MAIN
      RESULTS: Four studies, with a total of 204 participants were included and
      analysed. The trials compared metoclopramide with placebo (two trials) or with no
      intervention (two trials). Metoclopramide was investigated at doses of 10 mg (two
      trials) and 20 mg (two trials). There was no statistically significant difference
      between metoclopramide versus placebo or no intervention administered to promote
      tube placement (RR 0.82, 95% CI 0.61 to 1.10). Metoclopramide at doses of 10 mg
      (RR 0.82, 95% CI 0.60 to 1.11) and 20 mg (RR 0.62, 95% CI 0.15 to 2.62) were
      equally ineffective in facilitating post-pyloric intubation when compared with
      placebo or no intervention. AUTHORS' CONCLUSIONS: In this review, we found only
      four studies that fitted our inclusion criteria. These were small, underpowered
      studies, in which metoclopramide was given at doses of 10 mg and 20 mg. Our
      analysis showed that metoclopramide did not assist post-pyloric placement of naso
      enteral feeding tubes.Ideally randomised clinical trials should be performed that
      have a significant sample size, administering metoclopramide against control,
      however, given the lack of efficacy revealed by this review it is unlikely that
      further studies will be performed.

PMID- 25564771
TI  - Nonalcoholic fatty liver disease: Fibrosis portends a worse prognosis.

PMID- 25564772
TI  - Low filaggrin monomer repeats in African American pediatric patients with
      moderate to severe atopic dermatitis.

PMID- 25564773
TI  - Atomically thin arsenene and antimonene: semimetal-semiconductor and indirect
      direct band-gap transitions.
AB  - The typical two-dimensional (2D) semiconductors MoS2, MoSe2, WS2, WSe2 and black
      phosphorus have garnered tremendous interest for their unique electronic,
      optical, and chemical properties. However, all 2D semiconductors reported thus
      far feature band gaps that are smaller than 2.0 eV, which has greatly restricted
      their applications, especially in optoelectronic devices with photoresponse in
      the blue and UV range. Novel 2D mono-elemental semiconductors, namely monolayered
      arsenene and antimonene, with wide band gaps and high stability were now
      developed based on first-principles calculations. Interestingly, although As and
      Sb are typically semimetals in the bulk, they are transformed into indirect
      semiconductors with band gaps of 2.49 and 2.28 eV when thinned to one atomic
      layer. Significantly, under small biaxial strain, these materials were
      transformed from indirect into direct band-gap semiconductors. Such dramatic
      changes in the electronic structure could pave the way for transistors with high
      on/off ratios, optoelectronic devices working under blue or UV light, and
      mechanical sensors based on new 2D crystals.

PMID- 25564776
TI  - The diagnostic value of diffusion-weighted imaging and the apparent diffusion
      coefficient values in the differentiation of benign and malignant breast lesions.
AB  - INTRODUCTION: The goal of our study was to evaluate the diagnostic efficacy of
      diffusion-weighted imaging (DWI) in the differentiation of benign and malignant
      breast lesions. METHODS: Between June 2012 and March 2013, 60 patients with 63
      lesions (age range 29-70 years, mean age 48.6 years) were included in our study.
      All lesions, except complicated cysts and intra-mammary lymph nodes, were
      confirmed histopathologically. The patients were evaluated with a 1.5 Tesla MR
      scanner using dedicated bilateral breast coil. DWI images were obtained by echo
      planar imaging sequence and 'b' values were selected as 200, 600 and 1000
      s/mm(2). Apparent diffusion coefficient (ADC) values of both breast lesions and
      the normal fibroglandular tissue of the contralateral breast were calculated and
      statistically compared using Shapiro-Wilk test, Student's t-test, Mann-Whitney U
      test, chi-square test and the receiver operating curve. RESULTS: Of 63 lesions,
      22 were malignant and 41 were benign. In malignant lesions, the mean ADC values
      were 1.40 +/- 0.41 * 10(-3) mm(2)/s for b = 200, 1.05 +/- 0.28 * 10(-3) mm(2)/s
      for b = 600 and 0.91 +/- 0.20 * 10(-3) mm(2)/s for b = 1000 and in benign
      lesions, the mean ADC values were 2.13 +/- 0.85 * 10(-3) mm(2)/s for b = 200,
      1.64 +/- 0.47 * 10(-3) mm(2)/s for b = 600 and 1.40 +/- 0.43 * 10(-3) mm(2)/s for
      b = 1000. The success of ADC values in differentiation of benign and malignant
      lesions was statistically significant (P = 0.0001). The threshold values were
      determined to be 1.50 * 10(-3) mm(2)/s for b = 200, 1.22 * 10(-3) mm(2)/s for b =
      600 and 0.98 * 10(-3) mm(2)/s for b = 1000 (P < 0.05). CONCLUSION: DWI can be an
      effective radiological method in the differentiation of benign and malignant
      breast lesions.

PMID- 25564774
TI  - Health behaviors of minority childhood cancer survivors.
AB  - BACKGROUND: Available data have suggested that childhood cancer survivors (CCSs)
      are comparable to the general population with regard to many lifestyle
      parameters. However, to the authors' knowledge, little is known regarding
      minority CCSs. This cross-sectional study describes and compares the body mass
      index and health behaviors of African American, Hispanic, and white survivors
      with each other and with noncancer controls. METHODS: Participants included 452
      adult CCSs (150 African American, 152 Hispanic, and 150 white individuals)
      recruited through 4 childhood cancer treating institutions and 375 ethnically
      matched noncancer controls (125 in each racial/ethnic group) recruited via
      targeted digit dial. All participants completed a 2-hour in-person interview.
      RESULTS: Survivors and noncancer controls reported similar health behaviors.
      Within survivors, smoking and physical activity were found to be similar across
      racial/ethnic groups. African American and Hispanic survivors reported lower
      daily alcohol use compared with white individuals, but consumed unhealthy diets
      and were more likely to be obese. CONCLUSIONS: This unique study highlights that
      many minority CCSs exhibit lifestyle profiles that contribute to an increased
      risk of chronic diseases and late effects. Recommendations for behavior changes
      must consider the social and cultural context in which minority survivors may
      live.

PMID- 25564778
TI  - Online teaching of inflammatory skin pathology by a French-speaking International
      University Network.
AB  - INTRODUCTION: Developments in technology, web-based teaching and whole slide
      imaging have broadened the teaching horizon in anatomic pathology. Creating
      online learning material including many types of media such as radiologic images,
      whole slides, videos, clinical and macroscopic photographs, is now accessible to
      most universities. Unfortunately, a major limiting factor to maintain and update
      the learning material is the amount of resources needed. In this perspective, a
      French-national university network was initiated in 2011 to build joint online
      teaching modules consisting of clinical cases and tests. The network has since
      expanded internationally to Quebec, Switzerland and Ivory Coast. METHOD: One of
      the first steps of the project was to build a learning module on inflammatory
      skin pathology for interns and residents in pathology and dermatology. A
      pathology resident from Quebec spent 6 weeks in France and Switzerland to develop
      the contents and build the module on an e-learning Moodle platform under the
      supervision of two dermatopathologists. The learning module contains text,
      interactive clinical cases, tests with feedback, virtual slides, images and
      clinical photographs. For that module, the virtual slides are decentralized in 2
      universities (Bordeaux and Paris 7). Each university is responsible of its own
      slide scanning, image storage and online display with virtual slide viewers.
      RESULTS: The module on inflammatory skin pathology includes more than 50 web
      pages with French original content, tests and clinical cases, links to over 45
      virtual images and more than 50 microscopic and clinical photographs. The whole
      learning module is being revised by four dermatopathologists and two senior
      pathologists. It will be accessible to interns and residents in the spring of
      2014. The experience and knowledge gained from that work will be transferred to
      the next international resident whose work will be aimed at creating lung and
      breast pathology learning modules. CONCLUSION: The challenges of sustaining a
      project of this scope are numerous. The technical aspect of whole-slide imaging
      and storage needs to be developed by each university or group. The content needs
      to be regularly updated and its accuracy reviewed by experts in each individual
      domain. The learning modules also need to be promoted within the academic
      community to ensure maximal benefit for trainees. A collateral benefit of the
      project was the establishment of international partnerships between French
      speaking universities and pathologists with the common goal of promoting
      pathology education through the use of multi-media technology including whole
      slide imaging.

PMID- 25564779
TI  - Differences between state entropy and bispectral index during analysis of
      identical electroencephalogram signals: a comparison with two randomised
      anaesthetic techniques.
AB  - BACKGROUND: It is claimed that bispectral index (BIS) and state entropy reflect
      an identical clinical spectrum, the hypnotic component of anaesthesia. So far, it
      is not known to what extent different devices display similar index values while
      processing identical electroencephalogram (EEG) signals. OBJECTIVE: To compare
      BIS and state entropy during analysis of identical EEG data. Inspection of raw
      EEG input to detect potential causes of erroneous index calculation. DESIGN:
      Offline re-analysis of EEG data from a randomised, single-centre controlled trial
      using the Entropy Module and an Aspect A-2000 monitor. SETTING: Klinikum rechts
      der Isar, Technische Universitat Munchen, Munich. PATIENTS: Forty adult patients
      undergoing elective surgery under general anaesthesia. INTERVENTIONS: Blocked
      randomisation of 20 patients per anaesthetic group (sevoflurane/remifentanil or
      propofol/remifentanil). Isolated forearm technique for differentiation between
      consciousness and unconsciousness. MAIN OUTCOME MEASURES: Prediction probability
      (PK) of state entropy to discriminate consciousness from unconsciousness.
      Correlation and agreement between state entropy and BIS from deep to light
      hypnosis. Analysis of raw EEG compared with index values that are in conflict
      with clinical examination, with frequency measures (frequency bands/Spectral Edge
      Frequency 95) and visual inspection for physiological EEG patterns (e.g. beta or
      delta arousal), pathophysiological features such as high-frequency signals
      (electromyogram/high-frequency EEG or eye fluttering/saccades), different types
      of electro-oculogram or epileptiform EEG and technical artefacts. RESULTS: PK of
      state entropy was 0.80 and of BIS 0.84; correlation coefficient of state entropy
      with BIS 0.78. Nine percent BIS and 14% state entropy values disagreed with
      clinical examination. Highest incidence of disagreement occurred after state
      transitions, in particular for state entropy after loss of consciousness during
      sevoflurane anaesthesia. EEG sequences which led to false 'conscious' index
      values often showed high-frequency signals and eye blinks. High-frequency
      EEG/electromyogram signals were pooled because a separation into EEG and fast
      electro-oculogram, for example eye fluttering or saccades, on the basis of a
      single EEG channel may not be very reliable. These signals led to higher Spectral
      Edge Frequency 95 and ratio of relative beta and gamma band power than EEG
      signals, indicating adequate unconscious classification. The frequency of other
      artefacts that were assignable, for example technical artefacts, movement
      artefacts, was negligible and they were excluded from analysis. CONCLUSION: High
      frequency signals and eye blinks may account for index values that falsely
      indicate consciousness. Compared with BIS, state entropy showed more false
      classifications of the clinical state at transition between consciousness and
      unconsciousness.

PMID- 25564780
TI  - PREPARE: the prevalence of perioperative anaemia and need for patient blood
      management in elective orthopaedic surgery: a multicentre, observational study.
AB  - BACKGROUND: Patient blood management (PBM) can prevent preoperative anaemia, but
      little is known about practice in Europe. OBJECTIVE: To assess the pre and
      postoperative prevalence and perioperative management of anaemia in patients
      undergoing elective orthopaedic surgery in Europe. DESIGN: An observational
      study; data were collected from patient records via electronic case report forms.
      SETTING: Seventeen centres in six European countries. Centres were stratified
      according to whether they had a PBM programme or not. PATIENTS: One thousand five
      hundred and thirty-four patients undergoing major elective hip, knee or spine
      surgery [49.9% hip, 37.2% knee, 13.0% spine; age 64.0 years (range 18 to 80),
      61.3% female]. MAIN OUTCOME MEASURES: Prevalence of preoperative (primary
      endpoint) and postoperative anaemia [haemoglobin (Hb) <13 g dl (male), Hb <12 g
      dl (female)], perioperative anaemia management, time to first blood transfusion
      and number of transfused units. Data are shown as mean (SD) or median
      (interquartile range). RESULTS: Anaemia prevalence increased from 14.1%
      preoperatively to 85.8% postoperatively. Mean Hb decrease was 1.9 (1.5) and 3.0
      (1.3) g dl in preoperatively anaemic and nonanaemic patients, respectively (P <
      0.001). In PBM (n = 7) vs. non-PBM centres, preoperative anaemia was less
      frequent (8.0 vs. 18.5%; P < 0.001) and iron status was assessed more frequently
      (ferritin 11.0 vs. 2.6%, transferrin saturation 11.0 vs. 0.1%; P < 0.001).
      Perioperative anaemia correction (mainly transfusion) was given to 34.3%.
      Intraoperatively, 14.8% of preoperatively anaemic and 2.8% of nonanaemic patients
      received transfusions [units per patient: 2.4 (1.5) and 2.2 (1.4), median time to
      first intraoperative transfusion: 130 (88, 158) vs. 179 (135, 256) min; P <
      0.001]. Postoperative complications were more frequent in preoperatively anaemic
      vs. nonanaemic patients (36.9 vs. 22.2%; P = 0.009). CONCLUSION: Most patients
      who underwent elective orthopaedic surgery had normal preoperative Hb levels but
      became anaemic after the procedure. Those who were anaemic prior to surgery had
      an increased intraoperative transfusion risk and postoperative complication rate.
      PBM measures such as iron status assessment and strategies to avoid transfusion
      are still underused in Europe.

PMID- 25564777
TI  - The potential for emerging therapeutic options for Clostridium difficile
      infection.
AB  - Clostridium difficile is mainly a nosocomial pathogen and is a significant cause
      of antibiotic-associated diarrhea. It is also implicated in the majority of cases
      of pseudomembranous colitis. Recently, advancements in next generation sequencing
      technology (NGS) have highlighted the extent of damage to the gut microbiota
      caused by broad-spectrum antibiotics, often resulting in C. difficile infection
      (CDI). Currently the treatment of choice for CDI involves the use of
      metronidazole and vancomycin. However, recurrence and relapse of CDI, even after
      rounds of metronidazole/vancomycin administration is a problem that must be
      addressed. The efficacy of alternative antibiotics such as fidaxomicin,
      rifaximin, nitazoxanide, ramoplanin and tigecycline, as well as faecal microbiota
      transplantation has been assessed and some have yielded positive outcomes against
      C. difficile. Some bacteriocins have also shown promising effects against C.
      difficile in recent years. In light of this, the potential for emerging treatment
      options and efficacy of anti-C. difficile vaccines are discussed in this review. 

PMID- 25564782
TI  - A comparison of the disconnection technique with continuous bronchial suction for
      lung deflation when using the Arndt endobronchial blocker during video-assisted
      thoracoscopy: A randomised trial.
AB  - BACKGROUND: The use of the Arndt endobronchial blocker has not gained widespread
      acceptance during video-assisted thoracoscopic surgery (VATS) because of its high
      cost and longer time to operative lung collapse especially in patients with
      chronic obstructive pulmonary disease (COPD). The use of a ventilator
      disconnection technique has been shown to produce a comparable degree of lung
      collapse when used with either a double-lumen tube or an Arndt endobronchial
      blocker. OBJECTIVE: We hypothesised that the use of bronchial suction through the
      suction port of the endobronchial blocker would be associated with a comparable
      time to achieve optimum lung collapse as the disconnection technique. DESIGN: A
      randomised, double-blind study. SETTING: Single university hospital.
      PARTICIPANTS: Fifty-eight patients with spontaneous pneumothorax scheduled for
      elective VATS using the Arndt endobronchial blocker for one-lung ventilation
      (OLV). INTERVENTIONS: Patients were randomly assigned to one of two groups (n =
      29 per group) to deflate the operative lung with either disconnection of the
      endotracheal tube from the ventilator for 60 s prior to inflation of the
      endobronchial blocker or connection of a suction pressure of -30 cmH2O to the
      suction port of the endobronchial blocker through the barrel of a 1 ml syringe.
      MAIN OUTCOME MEASURES: The primary outcome was the time to total lung collapse.
      Secondary outcomes included surgeon rating of lung collapse, overall surgeon
      satisfaction, need for further fibreoptic bronchial suction manoeuvres and
      intraoperative hypoxaemia. RESULTS: The bronchial suction technique was
      associated with a significantly shorter time to total lung collapse than the
      disconnection method [93 (95% confidence interval, 95% CI 81.3 to 103.7) vs. 197
      (95% CI 157.4 to 237) s respectively; P < 0.001]. Both the disconnection and
      bronchial suction groups had a comparable surgical rating of excellent lung
      collapse 40 min after the start of OLV (65.5 vs. 79.3%, respectively; P = 0.24),
      overall surgeon satisfaction [median (interquartile range, IQR) 9 (8 to 10) vs. 9
      (8 to 10) respectively; P = 0.90] and intraoperative hypoxaemia (3.5 vs. 0%,
      respectively; P = 0.32). No patient in the bronchial suction group needed further
      manoeuvres to collapse the surgical lung. Moreover, the presence of COPD showed a
      significant positive correlation with the time to total lung collapse (Spearman r
      = 0.564; P < 0.001). CONCLUSION: The use of continuous bronchial suction through
      the lumen of the Arndt blocker offers an effective method to accelerate lung
      collapse. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02030795.

PMID- 25564781
TI  - Increased tracheal cuff pressure during insertion of a transoesophageal
      echocardiography probe: A prospective, observational study.
AB  - BACKGROUND: Excessive tracheal cuff pressure reduces tracheal mucosal blood flow
      and increases tracheal morbidity. Inserting a transoesophageal echocardiography
      (TOE) probe has been shown to increase tracheal cuff pressure. OBJECTIVE: To
      evaluate the effect of inserting a TOE probe on tracheal cuff pressure and
      compare the effect in patients who received a single-lumen endotracheal tube
      (SLT) with those who received a double-lumen endotracheal tube (DLT). DESIGN: A
      prospective, observational study. SETTING: Single-centre trial, study period from
      October 2013 to January 2014. PATIENTS: Forty-four adult patients scheduled for
      elective cardiothoracic surgery requiring intraoperative TOE monitoring.
      INTERVENTIONS: After tracheal intubation with a SLT (n = 22) or DLT (n = 22), the
      tracheal cuff was inflated to 18 mmHg (25 cmH2O) with air. Tracheal cuff pressure
      was monitored continuously for 5 min after inserting the TOE probe. MAIN OUTCOME
      MEASURES: The primary endpoint was steady-state tracheal cuff pressure after
      insertion of the TOE probe. RESULTS: Median (interquartile range, IQR) tracheal
      cuff pressure stabilised at 3 (2 to 3) min in the SLT group and at 2 (1 to 3) min
      in the DLT group. Steady-state cuff pressure was significantly higher in the DLT
      group than that in the SLT group [36.7 (31.3 to 44.1) vs. 31.3 (29.6 to 35.7)
      cmH2O; (P = 0.03)]. Steady-state cuff pressure more than 40 cmH2O was observed in
      two patients (18.2%) in the SLT group and nine patients (40.9%) in the DLT group
      (P = 0.02). CONCLUSION: Insertion of a TOE probe increased tracheal cuff pressure
      in both the SLT and DLT groups. The increase in cuff pressure was greater in
      patients who received a DLT. Frequent measurement and adjustment of cuff pressure
      should be emphasised particularly when TOE is used in patients receiving a DLT.
      TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02034643.

PMID- 25564784
TI  - Synthesis methods to prepare single- and multi-core iron oxide nanoparticles for
      biomedical applications.
AB  - We review current synthetic routes to magnetic iron oxide nanoparticles for
      biomedical applications. We classify the different approaches used depending on
      their ability to generate magnetic particles that are either single-core
      (containing only one magnetic core, i.e. a single domain nanocrystal) or multi
      core (containing several magnetic cores, i.e. single domain nanocrystals). The
      synthesis of single-core magnetic nanoparticles requires the use of surfactants
      during the particle generation, and careful control of the particle coating to
      prevent aggregation. Special attention has to be paid to avoid the presence of
      any toxic reagents after the synthesis if biomedical applications are intended.
      Several approaches exist to obtain multi-core particles based on the coating of
      particle aggregates; nevertheless, the production of multi-core particles with
      good control of the number of magnetic cores per particle, and of the degree of
      polydispersity of the core sizes, is still a difficult task. The control of the
      structure of the particles is of great relevance for biomedical applications as
      it has a major influence on the magnetic properties of the materials. 

PMID- 25564783
TI  - Influence of preoperative vaccination on monocytic HLA-DR expression and
      postoperative infection rate of patients with upper aerodigestive tract cancer: A
      randomised trial.

PMID- 25564788
TI  - The tradition and future of JAMA Psychiatry.

PMID- 25564785
TI  - Descriptive and hedonic analyses of low-Phe food formulations containing corn
      (Zea mays) seedling roots: toward development of a dietary supplement for
      individuals with phenylketonuria.
AB  - BACKGROUND: Seedling roots of anthocyanin-rich corn (Zea mays) cultivars contain
      high levels of phenylalanine ammonia lyase (PAL) activity. The development of a
      natural dietary supplement containing corn roots could provide the means to
      improve the restrictive diet of phenylketonuria (PKU) patients by increasing
      their tolerance to dietary phenylalanine (Phe). Therefore this research was
      undertaken to explore the sensory characteristics of roots of four corn cultivars
      as well as to develop and evaluate food products (cereal bar, beverage, jam-like
      spread) to which roots had been added. RESULTS: Sensory profiles of corn roots
      were investigated using ten trained judges. Roots of Japanese Striped corn
      seedlings were more bitter, pungent and astringent than those of white and yellow
      cultivars, while roots from the Blue Jade cultivar had a more pronounced
      earthy/mushroom aroma. Consumer research using 24 untrained panelists provided
      hedonic (degree-of-liking) assessments for products with and without roots
      (controls). The former had lower mean scores than the controls; however, the
      cereal bar had scores above 5 on the nine-point scale for all hedonic assessments
      compared with the other treated products. CONCLUSION: By evaluating low-Phe food
      products containing corn roots, this research ascertained that the root
      containing low-Phe cereal bar was an acceptable 'natural' dietary supplement for
      PKU-affected individuals.

PMID- 25564789
TI  - Association among posttraumatic stress disorder, adverse birth outcomes, and
      domestic violence.

PMID- 25564790
TI  - Ketamine for posttraumatic stress disorder.

PMID- 25564791
TI  - Ketamine for posttraumatic stress disorder--reply.

PMID- 25564797
TI  - A randomized, prospective, blinded, split-face, single-center study comparing
      polycaprolactone to hyaluronic acid for treatment of nasolabial folds.
AB  - BACKGROUND: Dermal fillers have continuingly been under development to increase
      safety, efficacy, and longevity. Biostimulatory dermal fillers, such as calcium
      hydroxylapatite fillers, have already been shown to be superior in efficacy
      compared to nonanimal stabilized hyaluronic acid (NASHA)-based fillers. AIMS: In
      this randomized split-face study, we compared a novel biostimulatory
      polycaprolactone (PCL)-based dermal filler with a NASHA-based dermal filler, for
      safety, efficacy, and duration of cosmetic correction for the treatment of
      nasolabial folds (NLFs). PATIENTS/METHODS: Forty subjects received a PCL-based
      dermal filler in one of their NLFs, and a NASHA-based dermal filler on the
      contralateral side. Efficacy was evaluated based on the Wrinkle Severity Rating
      Scale and Global Aesthetic Improvement Scale. RESULTS: After 6, 9, and 12 months
      post-treatment, NLFs treated with the PCL-based dermal filler showed
      statistically significant improvements on the Wrinkle Severity Rating Scale and
      greater improvements on the GAIS compared to NLFs treated with the NASHA-based
      dermal filler. Both products were found to be equally safe and well tolerated.
      CONCLUSION: Our results suggest that PCL-based dermal fillers offer longer
      lasting performance over NASHA-based dermal fillers in NLFs treatment.

PMID- 25564796
TI  - Strategies for improving diagnostic accuracy of biliary strictures.
AB  - BACKGROUND: Brush cytology is the initial intervention when evaluating biliary
      strictures. Biliary brush cytology is known for its low sensitivity (but high
      specificity) and may be accompanied by biopsies and/or fluorescent in situ
      hybridization (FISH) to improve diagnostic yield. This study aimed to identify
      features to enhance cytological sensitivity, and assess which sampling method(s)
      improve identification of pancreatobiliary adenocarcinomas (PBCa). METHODS:
      Seventy-three biliary stricture cases were retrieved (38 PBCa and 35 control
      benign strictures). Biliary brushings, FISH, and biopsies were reviewed. Cytology
      specimens were evaluated for cellularity and presence of drunken honeycomb (DH),
      loosely cohesive clusters of round cells (LCCRC), large atypical cells with foamy
      cytoplasm (LACF), and single vacuolated malignant cells (SCs). Biopsies were
      examined for the presence of stromal invasion (SI). RESULTS: Biliary brushings
      were scantly cellular in 47.4% of PBCa and 51.4% of controls, resulting in 69.6%
      nondiagnostic/false-negative cytology diagnoses. DH, LACF, and SCs were
      significantly associated with adenocarcinoma (P < .00001, .0033, and .00002,
      respectively). By univariate analysis, SCs and LACF were predictors of malignancy
      in brushings (P = .0002 and .05). By multivariate analysis, only SCs were
      predictive of malignancy (P = .002). SI facilitated the diagnosis in 9 biopsies.
      Sensitivity/specificity of brush cytology, FISH, and biopsy were 39.5%/94.3%,
      63.9%/94.3%, and 84.2%/100%, respectively. CONCLUSIONS: The low sensitivity of
      biliary brushings results from limited cellularity. Identification of LACF, DH,
      and SCs improves sensitivity. Sampling of stromal tissue may facilitate PBCa
      diagnosis. Concurrent biopsies and FISH are helpful in enhancing the diagnostic
      yield of PBCa.

PMID- 25564798
TI  - Inherent dynamics within the Crimean-Congo Hemorrhagic fever virus protease are
      localized to the same region as substrate interactions.
AB  - Crimean-Congo Hemorrhagic fever virus (CCHFV) is one of several lethal viruses
      that encodes for a viral ovarian tumor domain (vOTU), which serves to cleave and
      remove ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) from
      numerous proteins involved in cellular signaling. Such manipulation of the host
      cell machinery serves to downregulate the host response and, therefore, complete
      characterization of these proteases is important. While several structures of the
      CCHFV vOTU protease have been solved, both free and bound to Ub and ISG15, few
      structural differences have been found and little insight has been gained as to
      the structural plasticity of this protease. Therefore, we have used NMR
      relaxation experiments to probe the dynamics of CCHFV vOTU, both alone and in
      complex with Ub, discovering a highly dynamic protease that exhibits
      conformational exchange within the same regions found to engage its Ub substrate.
      These experiments reveal a structural plasticity around the N-terminal regions of
      CCHFV vOTU, which are unique to vOTUs, and provide a rationale for engaging
      multiple substrates with the same binding site. 

PMID- 25564799
TI  - Tunable loading of oligonucleotides with secondary structure on gold
      nanoparticles through a pH-driven method.
AB  - This paper describes how pH can be used to control covalent attachment of
      oligonucleotides with secondary structure on gold nanoparticles (AuNPs). The
      highest loading of thiolated nucleic acids occurred at low pH (pH = 1.7) due to
      reduced repulsion between the negatively charged oligonucleotides and the AuNP
      surface. The packing of oligonucleotides at low pH decreased (single-stranded ?
      duplex > quadruplex) as the spatial footprint of secondary structure increased.
      As the pH increased, a decrease in the number of DNA strands grafted to the AuNPs
      was observed. Notably, the loading density depended on the flexibility and
      spatial organization of the secondary structures at all pH conditions. At the
      lowest pH tested, circular dichroism analysis revealed that G-quadruplex aptamers
      underwent a structural change (from parallel to antiparallel or vice versa),
      although the biological activity of the aptamer-loaded AuNPs was still
      maintained. We anticipate that pH-tuning can result in quantitative loading of
      oligonucleotides on various types of AuNPs with different shapes and surface
      capping layers. 

PMID- 25564802
TI  - Clinical relevance of esophageal baseline impedance measurement: just an innocent
      bystander.
AB  - OBJECTIVE: The clinical relevance of esophageal baseline impedance (BI) remains
      to be determined. In the present study, we explored the impact of
      gastroesophageal reflux disease (GERD) and esophageal dysmotility on BI. METHODS:
      A total of 18 children with esophageal atresia, 26 children with GERD, and 17
      controls prospectively underwent esophagogastroduodenoscopy and pH-impedance
      monitoring. BI was measured in both proximal and distal esophagus.
      Gastroesophageal reflux (GER) and bolus transit indicators were defined according
      to published criteria. RESULTS: Patients with esophageal atresia showed
      significantly lower proximal and distal BI values (952 [716-1811] Omega; 895 [284
      1189] Omega; respectively) compared with those with GERD (3015 [2368-3975] Omega;
      2231 [1770-3032] Omega, P < 0.001 and <0.001, respectively) and controls (3699
      [3194-4358] Omega; 3522 [2927-3994] Omega, P < 0.001 and <0.001, respectively).
      Using linear regression, proximal BI strongly correlated with total bolus transit
      time (r(2) = 0.61, P < 0.001) and bolus presence time (BPT; r(2) = 0.63, P <
      0.001). Distal BI weakly correlated with acid exposure time (r(2) = 0.16, P <
      0.01) and longstanding reflux episodes (r(2) = 0.17, P < 0.01), and strongly
      correlated with total bolus transit time (r(2) = 0.53, P < 0.001) and BPT (r(2) =
      0.58, P < 0.001). By logistic regression, BPT predicted low proximal BI values
      (odds ratio [OR] 1.052; P < 0.05), whereas both GER indicators (acid exposure
      time: OR 1.56, P < 0.05; longstanding reflux episodes: OR 2.8, P < 0.05) and BPT
      (OR 1.66, P < 0.01) predicted low distal BI values. CONCLUSIONS: Along the length
      of esophagus, both bolus transit variables and GER significantly affect BI. This
      suggests that BI may merely mirror phenomena occurring within the esophageal
      lumen or wall, limiting its value as a discrete clinical entity to replace
      variables already used for assessing both GERD and esophageal dysmotility.

PMID- 25564803
TI  - Coeliac disease and noncoeliac gluten sensitivity.
AB  - The spectrum of gluten-related disorders was restricted to coeliac disease and
      wheat allergy, but the new contemporary entity referred to as noncoeliac gluten
      sensitivity has gained recognition mainly in adults but also in children.
      Noncoeliac gluten sensitivity is defined as the presence of a variety of symptoms
      related to gluten ingestion in patients in whom coeliac disease and wheat allergy
      have been excluded. The pathophysiology and biomarkers of coeliac disease and
      wheat allergy are well known, but this is not the case for noncoeliac gluten
      sensitivity. It is also not clear whether noncoeliac gluten sensitivity is caused
      by consumption of gluten or by consumption of fermentable oligosaccharides,
      disaccharides, monosaccharides, and polyols. Randomized trials on noncoeliac
      gluten sensitivity in children are lacking and are hardly needed to evaluate its
      role in paediatric patients with gastroenterology to avoid the use of unnecessary
      restrictive diets in children and interference with proper diagnosis of coeliac
      disease. 

PMID- 25564801
TI  - Infliximab "Top-Down" Strategy is Superior to "Step-Up" in Maintaining Long-Term
      Remission in the Treatment of Pediatric Crohn Disease.
AB  - OBJECTIVES: We aimed to compare the efficacy of remission maintenance between
      infliximab "top-down" and "step-up" strategies in moderate to severe pediatric
      Crohn disease during 3 years. We also aimed to determine prognostic factors that
      may influence the relapse-free rate in these patients. METHODS: The present study
      was a retrospective review of a prospective cohort, based on an infliximab
      treatment protocol for pediatric Crohn disease used at Samsung Medical Center. A
      total of 31 patients (group A) were treated with early infliximab induction ("top
      down" strategy) and 20 patients (group B) refractory to conventional therapy
      underwent infliximab treatment ("step-up" strategy). The efficacy of infliximab
      treatment was assessed by relapse-free rate and remission period rate for 3
      years. A total of 11 prognostic factors that may influence the relapse-free rate
      were further analyzed. RESULTS: The relapse-free rates at 3 years were 35.5% (95%
      confidence interval [CI] 0.194-0.519) in group A and 15.0% (95% CI 0.037-0.335)
      in group B (P = 0.0094). Overall remission period rate for 3 years also showed a
      significant difference between the 2 groups (92.1%  +/- 7.2% vs 78.3%  +/- 16.6%;
      P = 0.005). Multivariable analysis revealed that the duration from the initial
      diagnosis to infliximab infusion was the only factor associated with relapse-free
      remission for 3 years (hazard ratio = 1.077; 95% CI 1.025-1.131). CONCLUSIONS:
      "Top-down" strategy had a longer remission period compared with the "step-up"
      strategy in pediatric Crohn disease during a study period of 3 years, based on
      relapse-free rate and remission period rate. Earlier introduction of infliximab
      is recommended in pediatric patients with moderate to severe Crohn disease.

PMID- 25564804
TI  - Monotherapy with infliximab versus combination therapy in the maintenance of
      clinical remission in children with moderate to severe Crohn disease.
AB  - OBJECTIVES: The aim of the present study was to compare the efficacy and safety
      of 2 protocols of maintenance therapy with infliximab (IFX) and an
      immunomodulatory agent in pediatric patients with Crohn disease (CD): withdrawal
      of immunomodulators versus continuation of immunosuppressants. METHODS: The
      present multicenter randomized open-label trial included 99 patients with CD
      (ages 14.5 +/- 2.6 years) who were administered IFX (5 mg/kg body weight) along
      with an immunomodulatory agent (azathioprine 1.5-3 mg/kg body weight per day,
      methotrexate 10-25 mg/week). After 10 weeks of the induction therapy, 84
      responders were centrally randomized into 1 of the following groups: group I (n =
      45) in which IFX and an immunomodulatory agent were continued up to week 54 and
      group II (n = 39) in which the immunomodulatory agent was discontinued after 26
      weeks. RESULTS: The induction therapy was reflected by a significant decrease in
      Pediatric Crohn's Disease Activity Index (PCDAI) and Simplified Endoscopic
      Activity Score for Crohn's Disease (SES-CD) values. After the maintenance phase,
      the analyzed groups did not differ significantly in terms of the clinical
      response loss rates and final PCDAI and SES-CD scores. Furthermore, no
      significant intragroup differences were documented between mean PCDAI scores
      determined at the end of induction and maintenance phases.
      Intensification/modification of the treatment was required in 13 of 45 (29%) and
      11 of 39 (28%) patients of groups I and II, respectively. A total of 9 serious
      adverse events were documented; none of the patients died during the trial.
      CONCLUSIONS: Twenty-six weeks likely represent the safe duration of combined
      IFX/immunomodulatory therapy in our sample of pediatric patients with CD.

PMID- 25564806
TI  - Previously Undescribed Family Mutation in the JAG1 Gene as a Cause for Alagille
      Syndrome.

PMID- 25564805
TI  - Laboratory procedures update on Hirschsprung disease.
AB  - OBJECTIVES: The detection of ganglion cells in rectal biopsies of infants or
      toddlers with severe constipation is routinely performed by pediatric
      pathologists in many institutions. Hirschsprung disease (HD) is defined by the
      lack of ganglion cells (aganglionosis). The early recognition and the prompt
      implementation of surgical procedures obviously protect infants affected with HD
      from potential life-threatening conditions, including enterocolitis and
      debilitating constipation. Image-based and non-image-based clinical techniques
      and some laboratory tests have been reevaluated along the years, but often
      fragmentarily. Immunohistochemical markers have been increasingly used in
      pathology laboratories to detect ganglion cells and nerve fibers. Recently,
      calretinin, a vitamin D-dependent calcium-binding protein with expression in
      ganglion cells and nerves, has been described as an adjunctive or primary
      diagnostic test in HD. The aim of the present study was to systematically
      summarize and update laboratory procedures targeting ganglion cells in rectal
      biopsies. METHODS: Procedures and tests have been reviewed and values of
      specificity and sensitivity have been calculated according to the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      RESULTS: Contrast enema has the lowest sensitivity and specificity of all of the
      3-index investigations under the lens: contrast enema, anorectal manometry, and
      biopsy with histology. The latter procedure seems to have the highest sensitivity
      and specificity. Acetylcholinesterase staining on fresh-frozen material has been
      found to have slightly higher rates of sensitivity and specificity when compared
      with hematoxylin and eosin only. Calretinin staining may be supportive for the
      diagnosis, although some cases with false-positivity may be of some concern.
      CONCLUSIONS: Hematoxylin and eosin with or without acetylcholinesterase remains
      the criterion standard according to our PRISMA-based data. In our opinion, the
      number of false-positive results with potential overtreatment may limit the
      increasing advocacy for calretinin staining. Both the "primum non nocere" dictum
      and the "loss aversion heuristic" need to be satisfied harmoniously by preventing
      harm from unnecessary surgery.

PMID- 25564807
TI  - Health-related quality of life in youth with Crohn disease: role of disease
      activity and parenting stress.
AB  - OBJECTIVES: Health-related quality of life (HRQOL) is an important, but
      understudied construct in pediatric inflammatory bowel disease. Family level
      predictors of HRQOL have been understudied as are the mechanisms through which
      disease activity affects HRQOL. The present study examines the relation between a
      family level factor (parenting stress) and HRQOL in youth with Crohn disease.
      Parenting stress is examined as a mechanism through which disease activity
      affects HRQOL. METHODS: A total of 99 adolescents with Crohn disease and their
      parents were recruited across 3 sites. Adolescents completed the IMPACT-III
      (inflammatory bowel disease-specific HRQOL). Parents completed the Pediatric
      Inventory for Parents, a measure of medically related parenting stress that
      assesses stress because of the occurrence of medical stressors and stress because
      of the perceived difficulty of stressors. Disease activity was obtained from
      medical records. RESULTS: Parenting stress because of the occurrence of medical
      stressors partially mediated the disease severity-HRQOL relation, reducing the
      relation between these variables from 49.67% to 31.58% (B= -0.56, P < 0.0001).
      Bootstrapping analysis confirmed that the indirect effect of disease severity on
      HRQOL via parenting stress significantly differed from zero. Parenting stress
      because of the perceived difficulty of medical stressors partially mediated the
      disease severity-HRQOL relation, reducing the relation from 49.67% to 30.29% (B= 
      0.55, P < 0.0001). The indirect effect was confirmed via bootstrapping
      procedures. CONCLUSIONS: As disease severity increased, parenting stress also
      increased, and adolescent HRQOL decreased. Parenting stress should be considered
      and assessed for along with medical factors as part of a comprehensive approach
      to improve HRQOL in adolescents with Crohn disease.

PMID- 25564808
TI  - Lactobacillus rhamnosus GG Dosage Affects the Adjuvanticity and Protection
      Against Rotavirus Diarrhea in Gnotobiotic Pigs.
AB  - OBJECTIVES: The use of immunostimulatory strains of probiotics as adjuvants has
      been increasingly recognized as a promising approach in enhancing vaccine
      immunogenicity; however, dose effects of probiotic adjuvants are not well
      defined. In the present study, we examined dose effects of a commonly used
      probiotic strain, Lactobacillus rhamnosus GG (LGG), on immunomodulation with 2
      different dosages. METHODS: Neonatal gnotobiotic pigs were inoculated with 2 oral
      doses of attenuated human rotavirus (AttHRV) vaccines and fed with 5 doses
      (LGG5X; total 2.1 * 10(6) colony-forming units) or 9 doses (LGG9X; total 3.2 *
      10(6) colony-forming units) of LGG, starting at 3 days of age. RESULTS: Both LGG
      feeding regimens enhanced the protection rate of AttHRV vaccine against diarrhea
      on virulent human rotavirus challenge. LGG5X, but not LGG9X, significantly
      enhanced rotavirus-specific intestinal memory B-cell responses to AttHRV; LGG5X
      also significantly enhanced virus-specific intestinal immunoglobulin A (IgA)
      antibody-secreting cell responses. Both regimens significantly enhanced rotavirus
      specific serum IgA antibody responses to AttHRV. They also enhanced rotavirus
      specific interferon-gamma-producing effector/memory T-cell responses to AttHRV
      vaccine, with LGG9X being more effective than LGG5X, and both regimens
      downregulated CD4+CD25-FoxP3+ regulatory T (Treg) cell responses in most lymphoid
      tissues examined prechallenge and postchallenge and maintained the
      CD4+CD25+FoxP3+ Treg population in the ileum and intraepithelial lymphocyte
      postchallenge. LGG9X, however, did not significantly reduce total CD4+CD25-FoxP3+
      Treg frequencies in the intestine and transforming growth factor-beta-producing
      and interleukin (IL)-10-producing Treg frequencies in the blood. CONCLUSIONS:
      These results indicate that LGG at both dosages functioned as effective probiotic
      adjuvant for AttHRV vaccine, but different dosages differentially modulated
      immune responses to favor either the mucosal IgA response (LGG5X) or the T-cell
      response (LGG9X).

PMID- 25564809
TI  - Early introduction of complementary foods in preterm infants.
AB  - OBJECTIVES: The aim of the present study was to determine the odds of early
      introduction of solid foods in a nationally representative sample of preterm
      infants when compared with term infants and to examine whether factors associated
      with early introduction are the same for preterm and term infants. METHODS: Our
      sample of 7650 came from the first wave of the Early Childhood Longitudinal
      Study, Birth Cohort (2001-2002). We performed multivariable logistic regression
      to determine whether preterm infants were introduced to solid foods more
      frequently before 4 months than term infants using adjusted age for preterm
      infants and chronological age for term infants. In a separate analysis in preterm
      infants, we used multivariable logistic regression to determine whether the
      factors associated with early introduction in term infants were the same in the
      preterm sample. RESULTS: Infants born 22 to 32 weeks' gestation had a 9.90 (95%
      confidence interval 5.54-18.0) odds of being fed solid food before 4 months
      compared with term infants, and infants born 33 to 36 weeks' gestation had a 6.19
      (95% confidence interval 4.58-8.36) odds. Race/ethnicity and maternal smoking
      were the only factors that predicted early solid feeding in both preterm and term
      infants; the remaining predictors differed. CONCLUSIONS: Preterm infants are
      significantly more likely to be introduced to complementary foods early compared
      with term infants. The predictors of early solid feeding differ for preterm
      infants. Given the health implications, specific guidelines for preterm infants
      should be developed and future research should examine predictors of early
      introduction in preterm infants.

PMID- 25564810
TI  - Sensory Processing Difficulties in Toddlers With Nonorganic Failure-to-Thrive and
      Feeding Problems.
AB  - OBJECTIVES: Failure-to-thrive is defined as an abnormally low weight and/or
      height for age. The term "nonorganic failure-to-thrive" (NOFT) has been used to
      describe "failure-to-thrive" without an obvious cause underlying the growth
      failure. The purpose of the present study was to compare sensory processing
      abilities between toddlers with NOFT and feeding problems and age-matched
      controls. METHODS: Toddlers with NOFT and feeding problems (N = 16) were
      recruited from the pediatric feeding clinic in a tertiary university hospital,
      and age-matched controls (N = 16) were recruited from community volunteers. They
      were evaluated for sensory processing ability using an Infant/Toddler Sensory
      Profile (ITSP), and for development of cognition, motor skills, and language
      using the Bayley Scales of Infant Development II and Sequenced Language Scale for
      Infants. Behavior at mealtime was evaluated using the Behavioral Pediatrics
      Feeding Assessment Scale. RESULTS: In the NOFT with feeding problems group,
      atypical performances were more frequently observed in 3 of 5 ITSP section items
      (tactile, vestibular, and oral) compared with those in the control group.
      Significant delayed development of cognition, motor skills, and language was
      observed in the NOFT with feeding problems group compared with that in the
      control group. In addition, children who showed 1 or more atypical performances
      in ITSP had delayed development in cognition, motor skills, and language.
      CONCLUSIONS: Sensory processing problems were more commonly observed in toddlers
      with feeding problems and growth deficiency. The present study could provide a
      preliminary evidence for a possible impact of the sensory processing problems on
      the feeding difficulties in toddlers with NOFT. Future large studies should be
      conducted to clarify the relation between sensory processing difficulties and
      feeding problems in toddlers.

PMID- 25564811
TI  - Overstated associations between fructose and nonalcoholic fatty liver disease.

PMID- 25564812
TI  - Role of transjugular intrahepatic portosystemic shunt in children with advanced
      intestinal failure associated liver disease and portal hypertension.

PMID- 25564813
TI  - Nonalcoholic fatty liver disease and dyslipidemia: the beleagured hepatocyte.

PMID- 25564814
TI  - Authors' response.

PMID- 25564815
TI  - Protected time: a vital ingredient for research career development.

PMID- 25564816
TI  - Celiac disease can be predicted by high levels of anti-tissue transglutaminase
      antibodies in population-based screening.
AB  - OBJECTIVES: The aim of the present study was to evaluate any potential
      correlation between anti-tissue transglutaminase antibodies of type
      immunoglobulin A (tTG-IgA) and the degree of gluten-induced enteropathy in
      children participating in a screening study for celiac disease (CD) and to assess
      to what extent the revised European Society for Pediatric Gastroenterology,
      Hepatology, and Nutrition (ESPGHAN) guidelines cover this group of patients.
      METHODS: The present study is a substudy of a cross-sectional CD screening study,
      Exploring the Iceberg of Celiacs in Sweden, a 2-phased study performed during
      2005 to 2006 and 2009 to 2010. The 13,279 participating children had a blood test
      obtained, and those with positive tTG-IgA were recommended a small intestinal
      biopsy. The tTG-IgA levels at the time of biopsy were compared with those at the
      assessment of the biopsy. RESULTS: There were 267 children included, of whom 230
      were diagnosed as having CD. Of all of the children, 67 children had low tTG-IgA
      levels (<5 U/mL), of whom 55% had Marsh 3 lesions. All of the children with tTG
      IgA levels exceeding 10 times the upper limit of normal values of 5 U/mL, that
      is, 50 U/mL, were diagnosed as having CD. Lowering the cutoff to 3 U/mL, all but
      1 child with 30 U/mL got CD diagnosis. CONCLUSIONS: By adopting the revised
      ESPGHAN criteria, biopsies could have been omitted in one-fourth of all of the
      patients. Our results indicate that the criteria may be useful even in screened
      children. Further studies are needed to confirm whether the 2012 ESPGHAN
      guidelines should be revised to also apply to the populations being screened.

PMID- 25564817
TI  - Dietary nucleotide and nucleoside exposure in infancy and atopic dermatitis,
      recurrent wheeze, and allergic sensitization.
AB  - We hypothesized that early life exposure to nucleotides and nucleosides lowers
      the risk of recurrent wheeze, atopic dermatitis, and allergic sensitization among
      n = 429 children. Concentrations in breast milk were established by high
      performance liquid chromatography; concentrations in formula milks were obtained
      from manufacturers. Questionnaires and home visits were used to assess outcomes.
      Adjusted odds ratios in the highest tertile compared with those in the lowest
      tertile of exposure ranged from 1.11 to 1.99 in predominantly formula-fed
      children, and from 0.40 to 0.53 in predominantly breast-fed children, but were
      not significant. Thus, we found no evidence for association between nucleotide
      and nucleoside exposure and the development of atopic outcomes in children up to
      2 years. 

PMID- 25564818
TI  - Diagnostic and Therapeutic Roles of Endoscopic Ultrasound in Pediatric
      Pancreaticobiliary Disorders.
AB  - OBJECTIVES: The diagnostic role of endoscopic ultrasound (EUS) in children has
      only recently been demonstrated, and that also to a lesser extent than in adults.
      Data on the technique's therapeutic indications remain scarce. We therefore
      sought to evaluate diagnostic and interventional EUS indications, safety, and
      impact in children with pancreaticobiliary disorders. METHODS: We retrospectively
      reviewed our single pediatric center records, covering a 14-year period. RESULTS:
      From January 2000 to January 2014, 52 EUS procedures were performed in 48
      children (mean age: 12 years; range: 2-17 years) with pancreaticobiliary
      disorders for the following indications: suspected biliary obstruction (n =
      20/52), acute/chronic pancreatitis (n = 20), pancreatic mass (n = 3), pancreatic
      trauma (n = 7), and ampullary adenoma (n = 2). EUS was found to have a positive
      impact in 51 of 52 procedures, enabling us to avoid endoscopic retrograde
      cholangiopancreatography (ERCP) (n = 13 biliary; n = 6 pancreatic), focusing
      instead on endotherapy (n = 7 biliary; n = 14 pancreatic) or reorienting therapy
      toward surgery (n = 7). EUS-guided fine-needle aspiration was carried out on 12
      patients for pancreatic tumor (n = 4), pancreatic cyst fluid analysis (n = 4),
      autoimmune pancreatitis (n = 2), and suspicion of biliary tumor (n = 2). A total
      of 13 therapeutic EUS procedures (11 children) were conducted, including 9
      combined EUS-ERCP procedures (7 children, mean age: 8 years, range: 4-11 years),
      3 EUS-guided pseudocyst drainage (2 children), and 1 EUS-guided transgastric
      biliary drainage. CONCLUSIONS: Our study reports on a large pediatric EUS series
      for diagnostic and therapeutic pancreaticobiliary disorders, demonstrating the
      impact of diagnostic EUS and affording insights into novel EUS and combined EUS
      ERCP therapeutic applications. We suggest considering EUS as a diagnostic and
      therapeutic tool in the management of pediatric pancreaticobiliary diseases.

PMID- 25564819
TI  - The gastrointestinal endoscopy competency assessment tool for pediatric
      colonoscopy.
AB  - OBJECTIVES: Validated assessment tools are required to support competency-based
      education. We aimed to assess the reliability and validity of the
      Gastrointestinal Endoscopy Competency Assessment Tool for Pediatric Colonoscopy
      (GiECATKIDS), an instrument developed by 41 North American experts using Delphi
      methodology. METHODS: GiECATKIDS consists of a 7-item global rating scale (GRS)
      and an 18-item checklist (CL). An attending physician assessed 104 colonoscopies
      performed at 3 North American hospitals by 56 endoscopists, including 25 novices
      (<50 previous procedures), 21 intermediates (50-250), and 10 advanced
      endoscopists (>500). Another observer rated procedures to assess interrater
      reliability using intraclass correlation coefficient (ICC). Test-retest
      reliability was measured with ICC comparing endoscopists' first and second
      procedure scores. Discriminative validity was examined by comparing experience
      level with scores. Concurrent validity was assessed by correlating scores with
      colonoscopy experience, cecal and terminal ileal intubation rates, and physician
      global assessment. RESULTS: Interrater reliability of the GiECATKIDS was high
      (total: ICC = 0.88; GRS: ICC = 0.79; CL: ICC = 0.89). Test-retest reliability was
      excellent (total: ICC = 0.94; GRS: ICC = 0.94; CL: ICC = 0.84). GiECATKIDS total,
      GRS, and CL scores differed significantly among novice, intermediate, and
      advanced endoscopists (P < 0.001). There was a significant positive correlation
      (P < 0.001) between scores and number of previous colonoscopies (total: rho =
      0.91, GRS: rho = 0.92, CL: rho = 0.84), cecal intubation rate (total: rho = 0.82,
      GRS: rho = 0.85, CL: rho = 0.77), ileal intubation rate (total: rho = 0.82, GRS:
      rho = 0.82, CL: rho = 0.80), and physician global assessment (total: rho = 0.95,
      GRS: rho = 0.94, CL: rho = 0.89). CONCLUSIONS: The GiECATKIDS demonstrates strong
      reliability and validity as a measure of performance of pediatric colonoscopy
      that can be used to support training and assessment.

PMID- 25564821
TI  - GATA6 Mutation: A Rare Genetic Cause of Hepatobiliary Disease.

PMID- 25564820
TI  - Factors Determining delta-Bilirubin Levels in Infants With Biliary Atresia.
AB  - OBJECTIVES: delta-Bilirubin (Bdelta) forms when bilirubin conjugates covalently
      bind to albumin by way of nonenzymatic transesterification in patients with
      cholestasis. Infants with cholestasis with biliary atresia form Bdelta. The aim
      of the present study was to investigate the factors determining serum Bdelta
      concentrations in infants with biliary atresia. METHODS: Study patients were
      infants enrolled in a prospective study (PROBE: Clinicaltrials.gov NCT00061828)
      of biliary atresia. We acquired data of concurrently measured serum bilirubin
      analytes (total bilirubin [TB], conjugated bilirubin [Bc], and unconjugated
      bilirubin) and applied graphical methods and linear mixed effects model to study
      factors contributing to Bdelta variability. RESULTS: Bdelta level increased with
      increasing levels of Bc and TB. In addition, the length of time cholestasis
      persisted partially determined the level of Bdelta. An increase of 1 mg/dL in Bc
      is related to approximately 0.36 mg/dL increase in Bdelta (P < 0.0001); every 100
      days of cholestasis is associated with an approximately 1.0 mg/dL increase in
      Bdelta (P < 0.0001) given the same level of Bc. Serum albumin levels are not
      significantly related to Bdelta (P = 0.89). CONCLUSIONS: Bdelta levels in infants
      with biliary atresia increase with increasing levels of Bc and longer duration of
      cholestasis. Understanding the relation among Bdelta, Bc, TB, and direct-reacting
      bilirubin levels can help in interpretation of the clinical extent of cholestasis
      in infants and children with biliary atresia, assisting in the diagnosis and
      management of these infants.

PMID- 25564822
TI  - Evidence-based diagnosis and treatment of functional constipation: "are we there
      yet?".

PMID- 25564823
TI  - Milk fat globule membrane: a case of throwing the baby out with the bathwater?

PMID- 25564824
TI  - CaMKII: do not work too hard in the failing heart.
AB  - CaMKIIdelta, a calcium/calmodulin-dependent protein kinase, plays pivotal roles
      in the development of heart disease. In this issue of The Journal of Pathology,
      Salma Awad and colleagues demonstrate that CaMKIIdelta is engaged in both
      pathological hypertrophy and heart failure. By analysis of mouse and human heart
      samples, they found that the level of CaMKIIdelta is increased in both
      pathological processes. Further studies demonstrated that CaMKIIdelta mediates
      the phosphorylation of histone H3 at serine 10 (H3S10), which then tethers the
      chaperone protein 14-3-3 to promoter regions of fetal cardiac genes to activate
      their transcription. Combined with recent highlights on transcription regulation,
      this study revealed a fuzzy boundary between pathological hypertrophy and
      subsequent heart failure and indicates that current therapeutic strategies
      towards heart failure may have potential risks to patients.

PMID- 25564825
TI  - Rapid identification of erythrocyte phospholipids in Sprague-Dawley rats by ultra
      high performance liquid chromatography with electrospray ionization quadrupole
      time-of-flight tandem mass spectrometry.
AB  - A rapid, sensitive, and reliable approach for analyzing five kinds of erythrocyte
      phospholipids in Sprague-Dawley rats was provided by ultra high performance
      liquid chromatography coupled with electrospray ionization quadrupole time-of
      flight tandem mass spectrometry with MassLynx(TM) MassFragment. Improving
      conventional high performance liquid chromatography techniques, ultra high
      performance liquid chromatography integrated with quadrupole time-of-flight
      tandem mass spectrometry offers high sensitivity and increased analytical speed
      by using columns packed with sub-2 MUm particles (1.7 MUm), which allows a faster
      separation to be achieved. Through this method, 83 phospholipids were tentatively
      characterized based on their mass spectra and tandem mass spectra, as well as by
      matching the in-house formula database within a mass error of 5 ppm, including 40
      phosphatidylcholines, 24 phosphatidyl ethanolamines, three phosphatidylinositols,
      six phosphatidylserines, and ten sphingomyelins. Our present results proved that
      the established method could be used to qualitatively analyze complex erythrocyte
      phospholipids in Sprague-Dawley rats and provide a useful data base for
      pharmacology and phospholipidomics to seek potential biomarkers of disease
      prediction.

PMID- 25564827
TI  - Subjective social status and readiness to quit among homeless smokers.
AB  - OBJECTIVES: To explore the predictive value of subjective social status (SSS-US
      and SSS-Community) on readiness to quit among 245 homeless smokers. METHODS:
      Hierarchical multiple regression analyses were conducted (stratified by sex).
      RESULTS: Higher SSS-US (p = .02) and SSS-Community (p < .001) predicted greater
      readiness to quit in the total sample. These relationships upheld for men (p's <.
      01), but only SSS-Community predicted readiness to quit for women (p = .02).
      CONCLUSIONS: Higher SSS is associated with greater readiness to quit among
      homeless smokers. SSS-Community may be a more relevant index of SSS for women
      relative to SSS-US. Results suggest SSS may be a factor that contributes to
      smoking, disease, and health disparities.

PMID- 25564826
TI  - Properties of a commercial PTW-60019 synthetic diamond detector for the dosimetry
      of small radiotherapy beams.
AB  - A CVD based radiation detector has recently become commercially available from
      the manufacturer PTW-Freiburg (Germany). This detector has a sensitive volume of
      0.004 mm(3), a nominal sensitivity of 1 nC Gy(-1) and operates at 0 V. Unlike
      natural diamond based detectors, the CVD diamond detector reports a low dose rate
      dependence. The dosimetric properties investigated in this work were dose rate,
      angular dependence and detector sensitivity and linearity. Also, percentage depth
      dose, off-axis dose profiles and total scatter ratios were measured and compared
      against equivalent measurements performed with a stereotactic diode. A Monte
      Carlo simulation was carried out to estimate the CVD small beam correction
      factors for a 6 MV photon beam. The small beam correction factors were compared
      with those obtained from stereotactic diode and ionization chambers in the same
      irradiation conditions The experimental measurements were performed in 6 and 15
      MV photon beams with the following square field sizes: 10 * 10, 5 * 5, 4 * 4, 3 *
      3, 2 * 2, 1.5 * 1.5, 1 * 1 and 0.5 * 0.5 cm. The CVD detector showed an excellent
      signal stability (<0.2%) and linearity, negligible dose rate dependence (<0.2%)
      and lower response angular dependence. The percentage depth dose and off-axis
      dose profiles measurements were comparable (within 1%) to the measurements
      performed with ionization chamber and diode in both conventional and small
      radiotherapy beams. For the 0.5 * 0.5 cm, the measurements performed with the CVD
      detector showed a partial volume effect for all the dosimetric quantities
      measured. The Monte Carlo simulation showed that the small beam correction
      factors were close to unity (within 1.0%) for field sizes >=1 cm. The synthetic
      diamond detector had high linearity, low angular and negligible dose rate
      dependence, and its response was energy independent within 1% for field sizes
      from 1.0 to 5.0 cm. This work provides new data showing the performance of the
      CVD detector compared against a high spatial resolution diode. It also presents a
      comparison of the CVD small beam correction factors with those of diode and
      ionization chamber for a 6 MV photon beam. 

PMID- 25564828
TI  - Predicting general practice attendance for follow-up cancer care.
AB  - OBJECTIVE: To examine the role of the theory of planned behavior (TPB) in
      influencing patients' intention to attend follow-up visits with a general
      practitioner (GP). METHODS: A questionnaire based on the TPB was used to assess
      colorectal cancer (CRC) patients' intention to attend follow-up visits with a GP.
      RESULTS: TPB factors accounted for 43.3% of the variance of intention for follow
      up visits. Attitude alone explained 23.3% of the variance. Attitude and presence
      of other comorbidities significantly affected intention to visit a GP (attitude:
      R(2)=0.23, F [1, 65]=4.35, p < .01; comorbidity: R(2)=0.13, F [1, 65]=3.02, p <
      .05). CONCLUSION: Patients who believe their GP has the skills and knowledge to
      detect a recurrence and patients with other comorbidities have greater intention
      to visit their GP following treatment.

PMID- 25564829
TI  - Measurement properties of the sedentary behavior strategy self-management
      instrument in African-American breast cancer survivors.
AB  - OBJECTIVES: To examine the validity and reliability of a modified Sedentary
      Behavior Strategy Self-Management Scale (SBSMS) in a sample of breast cancer
      survivors. METHODS: A total of 291 African-American (AA) breast cancer survivors
      completed the SBSMS, which was subjected to tests of reliability, structural
      validity, and tests of measurement equivalence/invariance (ME/I). RESULTS: A
      revised measurement model fit the data and demonstrated internal reliability and
      structural validity. Tests for ME/I revealed that the revised model had
      appropriate levels of invariance among weight status, educational, and years out
      from diagnosis groups, but not among age groups. CONCLUSION: The reliability and
      structural validity of the instrument was supported overall; however, revisions
      may be needed to support its validity in older AA breast cancer survivors.

PMID- 25564830
TI  - Coping mediates the effects of depressive symptoms on sleep problems.
AB  - OBJECTIVES: To explore the relationships of perceived stress and depressive
      symptoms to sleep problems, testing for mediation by adaptive and maladaptive
      coping strategies. METHODS: Alternative high school students (N = 1676) completed
      self-report surveys. Cross-sectional data were analyzed via Preacher and Hayes'
      procedures for multiple mediation. RESULTS: The positive relationship between
      depressive symptoms and sleep problems was mediated partially by anger coping
      (positively related to sleep problems). The positive relationship between
      perceived stress and sleep problems was not mediated by coping strategies.
      CONCLUSIONS: Findings provide information on psychological factors that may lead
      to poor sleep outcomes, and are useful for developing health promotion
      interventions to impact lifelong health behaviors.

PMID- 25564831
TI  - Social support, stress, and suicidal ideation in professional firefighters.
AB  - OBJECTIVE: To hypothesize that social support may protect against the effect of
      firefighter stress on suicidal ideation. METHODS: Overall, 334 firefighters
      completed measures of occupational stress, social support, and suicidal ideation.
      RESULTS: At high levels of social support, no association was observed between
      occupational stress and suicidal ideation (phi = -.06, ns); however, when social
      support was low, occupational stress showed a positive association with suicidal
      ideation (phi = .16, p < .05). CONCLUSIONS: The association between occupational
      stress and suicidal ideation may be reduced by social support. Further research
      on this topic is warranted.

PMID- 25564832
TI  - Getting youth to Check it Out!(r): a new approach to teaching self-screening.
AB  - OBJECTIVES: To determine if intervention school students who received skills
      based breast self-exam (BSE)/testicular self-exam (TSE) training were more likely
      than control school students to report higher intentions to perform BSE/TSE,
      greater BSE/TSE self-efficacy, and actual performance of BSE/TSE. METHODS:
      BSE/TSE behaviors, intentions, and self-efficacy were assessed in a high school
      based trial (N = 6 schools; 3 schools randomized/condition) using self-reported
      data at 3 time points (N = 1058, 9 th grade students). RESULTS: At follow-up,
      intervention students had greater BSE/TSE intentions and self-efficacy than
      control students. Intervention students were more likely than control students to
      report monthly BSE (54.8% vs 27.2%, p = .031) and TSE (81.5% vs 31.4%, p = .010).
      CONCLUSIONS: Skills-based interventions with goal setting affect teenagers' self
      examination behaviors, intentions, and self-efficacy. Teaching self-screening may
      empower teenagers to become more engaged in their preventive health, which may
      lead to improved health as they age.

PMID- 25564834
TI  - Men's help-seeking behavior with regards to lower bowel symptoms.
AB  - OBJECTIVE: To explore the barriers to help-seeking among men experiencing lower
      bowel symptoms. METHODS: Semi-structured interviews were conducted with 13 men
      recruited via purposive sampling. Interviews were audio-taped, transcribed, and
      analyzed thematically. RESULTS: Misinterpretation of the symptoms and the
      attribution of the symptoms to non-medical causes were common barriers to help
      seeking. Other barriers include the cost of consulting a GP, llow level of
      confidence in consultation, and fear of cancer diagnosis. Some participants did
      not seek medical advice as the symptoms were intermittent or resolved with over
      the-counter medications. CONCLUSION: There is a need for health promotion
      campaigns for men with regards to seeking timely medical advice for lower bowel
      symptoms.

PMID- 25564833
TI  - HPV awareness, knowledge and attitudes among older African-American women.
AB  - OBJECTIVE: To assess correlates of human papillomavirus (HPV) awareness,
      knowledge, and attitudes among older, church-going African-American women.
      METHODS: Participants (N = 759), aged 40-80, answered survey questions about HPV
      awareness, knowledge, and attitudes toward vaccination of adolescent daughters.
      Associations between participant characteristics and HPV items were assessed
      using chi-square tests and logistic regression analyses. RESULTS: Younger age,
      higher education, a family history of cancer, and less spirituality were each
      associated with HPV awareness individually, and when considered jointly in a
      single model (p values <.038). Higher education was related to HPV knowledge (p =
      .006). CONCLUSIONS: African-American women of older age, less education, no
      family history of cancer, and/or higher spirituality might benefit from targeted
      church-based HPV educational campaigns.

PMID- 25564835
TI  - Health priorities among women recently released from jail.
AB  - OBJECTIVE: To describe the health priorities of women recently released from
      jail. METHOD: We open-coded semi-structured interview transcripts collected from
      28 women within 6 months after their release from jail to identify themes
      associated with prioritization of health. RESULTS: Five out of 28 women listed
      health as their top post-release priority. However, many women had competing
      priorities after release, including housing, employment, and children. We found
      that women described several reasons why health was not a priority; however,
      participants reported regular use of the healthcare system upon release from
      jail, indicating that health was important to them to some degree. CONCLUSIONS:
      Our findings from may inform intervention efforts that connect women to
      healthcare resources and increase health-promoting behavior during the transition
      from jail to community.

PMID- 25564837
TI  - Walk Score(TM), Perceived Neighborhood Walkability, and walking in the US.
AB  - OBJECTIVES: To investigate both the Walk Score(TM) and a self-reported measure of
      neighborhood walkability ("Perceived Neighborhood Walkability") as estimators of
      transport and recreational walking among Americans. METHODS: The study is based
      upon a survey of a nationally-representative sample of 1224 American adults. The
      survey gauged walking for both transport and recreation and included a self
      reported measure of neighborhood walkability and each respondent's Walk
      Score(TM). Binary logistic and linear regression analyses were performed on the
      data. RESULTS: The Walk Score(TM) is associated with walking for transport, but
      not recreational walking nor total walking. Perceived Neighborhood Walkability is
      associated with transport, recreational and total walking. CONCLUSIONS: Perceived
      Neighborhood Walkability captures the experiential nature of walking more than
      the Walk Score(TM).

PMID- 25564836
TI  - Social contingencies and college quit and win contest: a qualitative inquiry.
AB  - OBJECTIVES: To investigate the social contingencies associated with participation
      in a college Quit and Win contest to promote smoking cessation. METHODS: Six
      focus groups (N = 27) were conducted with college students who participated in a
      Quit and Win research trial. RESULTS: Themes included: (1) participants reluctant
      to disclose quit decision; (2) perception of little support in their quit
      attempt, and (3) the social environment as a trigger for relapse. CONCLUSIONS:
      Although Quit and Win contests appear to motivate an initial quit attempt, the
      reluctance of smokers to disclose their quit attempt limits the potential
      positive impact of social support when utilizing this public service campaign.

PMID- 25564838
TI  - Health behaviors and perceptions of cancer survivors harvesting at an urban
      garden.
AB  - OBJECTIVES: To gather information about perceptions of personal health behavior
      change in cancer survivors following participation in an urban gardening program.
      METHODS: This qualitative study used focus groups of adult cancer survivors with
      an open-ended question thread format. Data were transcribed and analyzed by
      identifying, coding, and categorizing primary patterns/themes. RESULTS: Four
      overarching themes were identified: (1) greater dietary intake of produce; (2)
      improved mental and physical health; (3) enhanced sense of community and social
      support; and (4) challenges to long-term maintenance. CONCLUSIONS: Perceptions of
      positive behavior changes associated with harvesting at an urban garden targeting
      cancer survivors may inform future community and health promotion interventions
      aimed at improving adherence to evidence-based lifestyle behavior guidelines for
      cancer survivorship.

PMID- 25564839
TI  - Adolescent girls' experiences in the Go Girls! group-based lifestyle mentoring
      program.
AB  - OBJECTIVE: To explore the experience of being in the Go Girls! program from the
      perspective of its participants. METHODS: Drawing from a social constructivist
      approach, this study consisted of semi-structured interviews conducted with 12
      purposively sampled Go Girls! participants. RESULTS: The results provided
      evidence for the emergence of 2 higher-order themes that subsume 7 lower-order
      themes and 27 categories that relate to the general components of the program and
      program outcomes associated with participating in the program. CONCLUSIONS:
      Participants in the Go Girls! program reported enjoying the program, experiencing
      changes in important health-enhancing cognitions and behaviors and developing
      meaningful relationships with program mentors and other program participants.

PMID- 25564840
TI  - Dual use of smokeless tobacco or e-cigarettes with cigarettes and cessation.
AB  - OBJECTIVES: To evaluate predictors of dual use of cigarettes with smokeless
      tobacco or e-cigarettes. METHODS: Adult smokers (N = 1324) completed online cross
      sectional surveys. Logistic regression evaluated predictors of dual use and
      cigarette quit attempts. RESULTS: Smokeless tobacco dual use was associated with
      past attempts to quit smoking by switching to smokeless products. E-cigarette
      dual use was associated with using stop-smoking medication and strong anti
      tobacco industry attitudes. Ever use of stop-smoking medication was associated
      with quit attempts among dual e-cigarette users and cigarette-only users.
      CONCLUSIONS: Dual users are more likely than cigarette-only users to endorse
      certain cessation-related attitudes and behaviors. This may provide an
      opportunity for clinicians or others to discuss evidence-based strategies for
      smoking cessation.

PMID- 25564841
TI  - Cultural beliefs and physical activity among African-American adolescents.
AB  - OBJECTIVE: To examine the association of cultural beliefs with physical activity
      (PA) among African-American adolescents. METHODS: For a list of 42 leisure-time
      physical activities, adolescents (N = 116) indicated whether they believed the
      activity was 'Mostly a Black Thing', 'Equally a Black and White Thing', or
      'Mostly a White Thing'. Moderate-to-vigorous physical activity was assessed using
      accelerometers. RESULTS: Participants scoring in the highest quartile of Mostly
      Black score engaged in more PA and were less likely to be overweight or obese
      compared to those in lower quartiles. However, these findings were not
      statistically significant. CONCLUSION: Further research to validate the
      association of cultural beliefs with PA is needed to inform health-enhancing PA
      interventions for this population.

PMID- 25564842
TI  - Action potential morphology of human induced pluripotent stem cell-derived
      cardiomyocytes does not predict cardiac chamber specificity and is dependent on
      cell density.
AB  - Previous studies investigating human induced pluripotent stem cell-derived
      cardiomyocytes (iPSC-CMs) have proposed the distinction of heart chamber-specific
      (atrial, ventricular, pacemaker) electrophysiological phenotypes based on action
      potential (AP) morphology. This suggestion has been based on data acquired using
      techniques that allow measurements from only a small number of cells and at low
      seeding densities. It has also been observed that density of culture affects the
      properties of iPSC-CMs. Here we systematically analyze AP morphology from iPSC
      CMs at two seeding densities: 60,000 cells/well (confluent monolayer) and 15,000
      cells/well (sparsely-seeded) using a noninvasive optical method. The confluent
      cells (n = 360) demonstrate a series of AP morphologies on a normally distributed
      spectrum with no evidence for specific subpopulations. The AP morphologies of
      sparsely seeded cells (n = 32) displayed a significantly different distribution,
      but even in this case there is no clear evidence of chamber-specificity.
      Reduction in gap junction conductance using carbenoxolone only minimally affected
      APD distribution in confluent cells. These data suggest that iPSC-CMs possess a
      sui generis AP morphology, and when observed in different seeding densities may
      encompass any shape including those resembling chamber-specific subtypes. These
      results may be explained by different functional maturation due to culture
      conditions. 

PMID- 25564843
TI  - Nanotube array method for studying lipid-induced conformational changes of a
      membrane protein by solid-state NMR.
AB  - Anodic aluminum oxide substrates with macroscopically aligned homogeneous
      nanopores of 80 nm in diameter enable two-dimensional, solid-state nuclear
      magnetic resonance studies of lipid-induced conformational changes of uniformly
      (15)N-labeled Pf1 coat protein in native-like bilayers. The Pf1 helix tilt angles
      in bilayers composed of two different lipids are not entirely governed by the
      membrane thickness but could be rationalized by hydrophobic interactions of
      lysines at the bilayer interface. The anodic aluminum oxide alignment method is
      applicable to a broader repertoire of lipids versus bicelle bilayer mimetics
      currently employed in solid-state nuclear magnetic resonance of oriented samples,
      thus allowing for elucidation of the role played by lipids in shaping membrane
      proteins. 

PMID- 25564844
TI  - Effects of cardiac Myosin binding protein-C on actin motility are explained with
      a drag-activation-competition model.
AB  - Although mutations in cardiac myosin binding protein-C (cMyBP-C) cause heart
      disease, its role in muscle contraction is not well understood. A mechanism
      remains elusive partly because the protein can have multiple effects, such as
      dual biphasic activation and inhibition observed in actin motility assays. Here
      we develop a mathematical model for the interaction of cMyBP-C with the
      contractile proteins actin and myosin and the regulatory protein tropomyosin. We
      use this model to show that a drag-activation-competition mechanism accurately
      describes actin motility measurements, while models lacking either drag or
      competition do not. These results suggest that complex effects can arise simply
      from cMyBP-C binding to actin. 

PMID- 25564845
TI  - Viral ssRNAs are indeed compact.

PMID- 25564846
TI  - Reading nanopore clocks in single-molecule electrophoresis experiments.

PMID- 25564847
TI  - The ghost in the machine: is the bacterial chromosome a phantom chain?

PMID- 25564848
TI  - Two is a pair, three is a network.

PMID- 25564849
TI  - Quantifying cell adhesion through impingement of a controlled microjet.
AB  - The impingement of a submerged, liquid jet onto a cell-covered surface allows
      assessing cell attachment on surfaces in a straightforward and quantitative
      manner and in real time, yielding valuable information on cell adhesion. However,
      this approach is insufficiently characterized for reliable and routine use. In
      this work, we both model and measure the shear stress exerted by the jet on the
      impingement surface in the micrometer-domain, and subsequently correlate this to
      jet-induced cell detachment. The measured and numerically calculated shear stress
      data are in good agreement with each other, and with previously published values.
      Real-time monitoring of the cell detachment reveals the creation of a circular
      cell-free area upon jet impingement, with two successive detachment regimes: 1),
      a dynamic regime, during which the cell-free area grows as a function of both the
      maximum shear stress exerted by the jet and the jet diameter; followed by 2), a
      stationary regime, with no further evolution of the cell-free area. For the
      latter regime, which is relevant for cell adhesion strength assessment, a
      relationship between the jet Reynolds number, the cell-free area, and the cell
      adhesion strength is proposed. To illustrate the capability of the technique, the
      adhesion strength of HeLa cervical cancer cells is determined ((34 +/- 14)
      N/m(2)). Real-time visualization of cell detachment in the dynamic regime shows
      that cells detach either cell-by-cell or by collectively (for which intact parts
      of the monolayer detach as cell sheets). This process is dictated by the cell
      monolayer density, with a typical threshold of (1.8 +/- 0.2) * 10(9) cells/m(2),
      above which the collective behavior is mostly observed. The jet impingement
      method presents great promises for the field of tissue engineering, as the
      influence of both the shear stress and the surface characteristics on cell
      adhesion can be systematically studied. 

PMID- 25564850
TI  - Two-bubble acoustic tweezing cytometry for biomechanical probing and stimulation
      of cells.
AB  - The study of mechanotransduction relies on tools that are capable of applying
      mechanical forces to elicit and assess cellular responses. Here we report a new
      (to our knowledge) technique, called two-bubble acoustic tweezing cytometry (TB
      ATC), for generating spatiotemporally controlled subcellular mechanical forces on
      live cells by acoustic actuation of paired microbubbles targeted to the cell
      adhesion receptor integrin. By measuring the ultrasound-induced activities of
      cell-bound microbubbles and the actin cytoskeleton contractile force responses,
      we determine that TB-ATC elicits mechanoresponsive cellular changes via cyclic,
      paired displacements of integrin-bound microbubbles driven by the attractive
      secondary acoustic radiation force (sARF) between the bubbles in an ultrasound
      field. We demonstrate the feasibility of dual-mode TB-ATC for both subcellular
      probing and mechanical stimulation. By exploiting the robust and unique
      interaction of ultrasound with microbubbles, TB-ATC provides distinct advantages
      for experimentation and quantification of applied forces and cellular responses
      for biomechanical probing and stimulation of cells. 

PMID- 25564851
TI  - A biomechanical model for fluidization of cells under dynamic strain.
AB  - Recent experiments have investigated the response of smooth muscle cells to
      transient stretch-compress (SC) and compress-stretch (CS) maneuvers. The results
      indicate that the transient SC maneuver causes a sudden fluidization of the cell
      while the CS maneuver does not. To understand this asymmetric behavior, we have
      built a biomechanical model to probe the response of stress fibers to the two
      maneuvers. The model couples the cross-bridge cycle of myosin motors with a
      viscoelastic Kelvin-Voigt element that represents the stress fiber. Simulation
      results point to the sensitivity of the myosin detachment rate to tension as the
      cause for the asymmetric response of the stress fiber to the CS and SC maneuvers.
      For the SC maneuver, the initial stretch increases the tension in the stress
      fiber and suppresses myosin detachment. The subsequent compression then causes a
      large proportion of the myosin population to disengage rapidly from actin
      filaments. This leads to the disassembly of the stress fibers and the observed
      fluidization. In contrast, the CS maneuver only produces a mild loss of myosin
      motors and no fluidization. 

PMID- 25564852
TI  - Mechanical amplification exhibited by quiescent saccular hair bundles.
AB  - Spontaneous oscillations exhibited by free-standing hair bundles from the
      Bullfrog sacculus suggest the existence of an active process that might underlie
      the exquisite sensitivity of the sacculus to mechanical stimulation. However,
      this spontaneous activity is suppressed by coupling to an overlying membrane,
      which applies a large mechanical load on the bundle. How a quiescent hair bundle
      utilizes its active process is still unknown. We studied the dynamics of motion
      of individual hair bundles under different offsets in the bundle position, and
      observed the occurrence of spikes in hair-bundle motion, associated with the
      generation of active work. These mechanical spikes can be evoked by a sinusoidal
      stimulus, leading to an amplified movement of the bundle with respect to the
      passive response. Amplitude gain reached as high as 100-fold at small stimulus
      amplitudes. Amplification of motion decreased with increasing amplitude of
      stimulation, ceasing at ~6-12 pN stimuli. Results from numerical simulations
      suggest that the adaptation process, mediated by myosin 1c, is not required for
      the production of mechanical spikes. 

PMID- 25564853
TI  - Probing binding sites and mechanisms of action of an I(Ks) activator by
      computations and experiments.
AB  - The slow delayed rectifier (IKs) channel is composed of the KCNQ1 channel and
      KCNE1 auxiliary subunit, and functions to repolarize action potentials in the
      human heart. IKs activators may provide therapeutic efficacy for treating long QT
      syndromes. Here, we show that a new KCNQ1 activator, ML277, can enhance IKs
      amplitude in adult guinea pig and canine ventricular myocytes. We probe its
      binding site and mechanism of action by computational analysis based on our
      recently reported KCNQ1 and KCNQ1/KCNE1 3D models, followed by experimental
      validation. Results from a pocket analysis and docking exercise suggest that
      ML277 binds to a side pocket in KCNQ1 and the KCNE1-free side pocket of
      KCNQ1/KCNE1. Molecular-dynamics (MD) simulations based on the most favorable
      channel/ML277 docking configurations reveal a well-defined ML277 binding space
      surrounded by the S2-S3 loop and S4-S5 helix on the intracellular side, and by S4
      S6 transmembrane helices on the lateral sides. A detailed analysis of MD
      trajectories suggests two mechanisms of ML277 action. First, ML277 restricts the
      conformational dynamics of the KCNQ1 pore, optimizing K(+) ion coordination in
      the selectivity filter and increasing current amplitudes. Second, ML277 binding
      induces global motions in the channel, including regions critical for KCNQ1
      gating transitions. We conclude that ML277 activates IKs by binding to an
      intersubunit space and allosterically influencing pore conductance and gating
      transitions. KCNE1 association protects KCNQ1 from an arrhythmogenic
      (constitutive current-inducing) effect of ML277, but does not preclude its
      current-enhancing effect. 

PMID- 25564854
TI  - Hrs and STAM function synergistically to bind ubiquitin-modified cargoes in
      vitro.
AB  - The turnover of integral membrane proteins requires a specialized transport
      pathway mediated by components of the endosomal sorting complex required for
      transport (ESCRT) machinery. In most cases, entry into this pathway requires that
      cargoes undergo ubiquitin-modification, thereby facilitating their sequestration
      on endosomal membranes by specific, ubiquitin-binding ESCRT subunits. However,
      requirements underlying initial cargo recognition of mono-ubiquitinated cargos
      remain poorly defined. In this study, we determine the capability of each ESCRT
      complex that harbors a ubiquitin-binding domain to bind a reconstituted integral
      membrane cargo (VAMP2), which has been covalently linked to mono-ubiquitin. We
      demonstrate that ESCRT-0, but not ESCRT-I or ESCRT-II, is able to associate
      stably with the mono-ubiquitinated cargo within a lipid bilayer. Moreover, we
      show that the ubiquitin-binding domains in both Hrs and STAM must be intact to
      enable cargo binding. These results indicate that the two subunits of ESCRT-0
      function together to bind and sequester cargoes for downstream sorting into
      intralumenal vesicles. 

PMID- 25564856
TI  - NMR-detected brownian dynamics of alphaB-crystallin over a wide range of
      concentrations.
AB  - Knowledge about the global translational and rotational motion of proteins under
      crowded conditions is highly relevant for understanding the function of proteins
      in vivo. This holds in particular for human alphaB-crystallin, which is strongly
      crowded in vivo and inter alia responsible for preventing cataracts. Quantitative
      information on translational and rotational diffusion is not readily available,
      and we here demonstrate an approach that combines pulsed-field-gradient NMR for
      translational diffusion and proton T1rho/T2 relaxation-time measurements for
      rotational diffusion, thus overcoming obstacles encountered in previous studies.
      The relaxation times measured at variable temperature provide a quantitative
      measure of the correlation function of protein tumbling, which cannot be
      approximated by a single exponential, because two components are needed for a
      minimal and adequate description of the data. We find that at high protein
      concentrations, rotational diffusion is decoupled from translational diffusion,
      the latter following the macroscopic viscosity change almost quantitatively,
      resembling the behavior of spherical colloids. Analysis of data reported in the
      literature shows that well-packed globular proteins follow a scaling relation
      between the hydrodynamic radius and the molar mass, Rh ~ M(1/d), with a fractal
      dimension of d ~ 2.5 rather than 3. Despite its oligomeric nature, Rh of alphaB
      crystallin as derived from both NMR methods is found to be fully consistent with
      this relation. 

PMID- 25564855
TI  - Mechanism of the alphabeta conformational change in F1-ATPase after ATP
      hydrolysis: free-energy simulations.
AB  - One of the motive forces for F1-ATPase rotation is the conformational change of
      the catalytically active beta subunit due to closing and opening motions caused
      by ATP binding and hydrolysis, respectively. The closing motion is accomplished
      in two steps: the hydrogen-bond network around ATP changes and then the entire
      structure changes via B-helix sliding, as shown in our previous study. Here, we
      investigated the opening motion induced by ATP hydrolysis using all-atom free
      energy simulations, combining the nudged elastic band method and umbrella
      sampling molecular-dynamics simulations. Because hydrolysis requires residues in
      the alpha subunit, the simulations were performed with the alphabeta dimer. The
      results indicate that the large-scale opening motion is also achieved by the B
      helix sliding (in the reverse direction). However, the sliding mechanism is
      different from that of ATP binding because sliding is triggered by separation of
      the hydrolysis products ADP and Pi. We also addressed several important issues:
      1), the timing of the product Pi release; 2), the unresolved half-closed beta
      structure; and 3), the ADP release mechanism. These issues are fundamental for
      motor function; thus, the rotational mechanism of the entire F1-ATPase is also
      elucidated through this alphabeta study. During the conformational change,
      conserved residues among the ATPase proteins play important roles, suggesting
      that the obtained mechanism may be shared with other ATPase proteins. When
      combined with our previous studies, these results provide a comprehensive view of
      the beta-subunit conformational change that drives the ATPase. 

PMID- 25564857
TI  - Quantitative mapping of protein structure by hydroxyl radical footprinting
      mediated structural mass spectrometry: a protection factor analysis.
AB  - Measurements from hydroxyl radical footprinting (HRF) provide rich information
      about the solvent accessibility of amino acid side chains of a protein.
      Traditional HRF data analyses focus on comparing the difference in the
      modification/footprinting rate of a specific site to infer structural changes
      across two protein states, e.g., between a free and ligand-bound state. However,
      the rate information itself is not fully used for the purpose of comparing
      different protein sites within a protein on an absolute scale. To provide such a
      cross-site comparison, we present a new, to our knowledge, data analysis
      algorithm to convert the measured footprinting rate constant to a protection
      factor (PF) by taking into account the known intrinsic reactivity of amino acid
      side chain. To examine the extent to which PFs can be used for structural
      interpretation, this PF analysis is applied to three model systems where
      radiolytic footprinting data are reported in the literature. By visualizing
      structures colored with the PF values for individual peptides, a rational view of
      the structural features of various protein sites regarding their solvent
      accessibility is revealed, where high-PF regions are buried and low-PF regions
      are more exposed to the solvent. Furthermore, a detailed analysis correlating
      solvent accessibility and local structural contacts for gelsolin shows a
      statistically significant agreement between PF values and various structure
      measures, demonstrating that the PFs derived from this PF analysis readily
      explain fundamental HRF rate measurements. We also tested this PF analysis on
      alternative, chemical-based HRF data, showing improved correlations of structural
      properties of a model protein barstar compared to examining HRF rate data alone.
      Together, this PF analysis not only permits a novel, to our knowledge, approach
      of mapping protein structures by using footprinting data, but also elevates the
      use of HRF measurements from a qualitative, cross-state comparison to a
      quantitative, cross-site assessment of protein structures in the context of
      individual conformational states of interest. 

PMID- 25564858
TI  - Unveiling prolyl oligopeptidase ligand migration by comprehensive computational
      techniques.
AB  - Prolyl oligopeptidase (POP) is a large 80 kDa protease, which cleaves
      oligopeptides at the C-terminal side of proline residues and constitutes an
      important pharmaceutical target. Despite the existence of several
      crystallographic structures, there is an open debate about migration (entrance
      and exit) pathways for ligands, and their coupling with protein dynamics. Recent
      studies have shown the capabilities of molecular dynamics and classical force
      fields in describing spontaneous binding events and nonbiased ligand migration
      pathways. Due to POP's size and to the buried nature of its active site, an
      exhaustive sampling by means of conventional long enough molecular dynamics
      trajectories is still a nearly impossible task. Such a level of sampling,
      however, is possible with the breakthrough protein energy landscape exploration
      technique. Here, we present an exhaustive sampling of POP with a known inhibitor,
      Z-pro-prolinal. In >3000 trajectories Z-pro-prolinal explores all the accessible
      surface area, showing multiple entrance events into the large internal cavity
      through the pore in the beta-propeller domain. Moreover, we modeled a natural
      substrate binding and product release by predicting the entrance of an
      undecapeptide substrate, followed by manual active site cleavage and nonbiased
      exit of one of the products (a dipeptide). The product exit shows preference from
      a flexible 18-amino acid residues loop, pointing to an overall mechanism where
      entrance and exit occur in different sites. 

PMID- 25564859
TI  - Estimating orientation factors in the FRET theory of fluorescent proteins: the
      TagRFP-KFP pair and beyond.
AB  - The orientation factor kappa(2), one of the key parameters defining Forster
      resonance energy transfer efficiency, is determined by the transition dipole
      moment orientations of the donor and acceptor species. Using the results of
      quantum chemical and quantum mechanical/molecular mechanical calculations for the
      chromophore-containing pockets in selected colored proteins of the green
      fluorescent protein family, we derived transition dipole moments corresponding to
      the S0,min -> S1 excitation for green fluorescent protein, red fluorescent
      protein (TagRFP), and kindling fluorescent protein, and the S1,min -> S0 emission
      for TagRFP. These data allowed us to estimate kappa(2) values for the TagRFP
      linker-kindling fluorescent protein tetrameric complex required for constructing
      novel sensors. 

PMID- 25564860
TI  - Cavity as a source of conformational fluctuation and high-energy state: high
      pressure NMR study of a cavity-enlarged mutant of T4 lysozyme.
AB  - Although the structure, function, conformational dynamics, and controlled
      thermodynamics of proteins are manifested by their corresponding amino acid
      sequences, the natural rules for molecular design and their corresponding
      interplay remain obscure. In this study, we focused on the role of internal
      cavities of proteins in conformational dynamics. We investigated the pressure
      induced responses from the cavity-enlarged L99A mutant of T4 lysozyme, using high
      pressure NMR spectroscopy. The signal intensities of the methyl groups in the
      (1)H/(13)C heteronuclear single quantum correlation spectra, particularly those
      around the enlarged cavity, decreased with the increasing pressure, and
      disappeared at 200 MPa, without the appearance of new resonances, thus indicating
      the presence of heterogeneous conformations around the cavity within the ground
      state ensemble. Above 200 MPa, the signal intensities of >20 methyl groups
      gradually decreased with the increasing pressure, without the appearance of new
      resonances. Interestingly, these residues closely matched those sensing a large
      conformational change between the ground- and high-energy states, at atmospheric
      pressure. (13)C and (1)H NMR line-shape simulations showed that the pressure
      induced loss in the peak intensity could be explained by the increase in the high
      energy state population. In this high-energy state, the aromatic side chain of
      F114 gets flipped into the enlarged cavity. The accommodation of the
      phenylalanine ring into the efficiently packed cavity may decrease the partial
      molar volume of the high-energy state, relative to the ground state. We suggest
      that the enlarged cavity is involved in the conformational transition to high
      energy states and in the volume fluctuation of the ground state. 

PMID- 25564861
TI  - Physical modeling of chromosome segregation in escherichia coli reveals impact of
      force and DNA relaxation.
AB  - The physical mechanism by which Escherichia coli segregates copies of its
      chromosome for partitioning into daughter cells is unknown, partly due to the
      difficulty in interpreting the complex dynamic behavior during segregation.
      Analysis of previous chromosome segregation measurements in E. coli demonstrates
      that the origin of replication exhibits processive motion with a mean
      displacement that scales as t(0.32). In this work, we develop a model for
      segregation of chromosomal DNA as a Rouse polymer in a viscoelastic medium with a
      force applied to a single monomer. Our model demonstrates that the observed power
      law scaling of the mean displacement and the behavior of the velocity
      autocorrelation function is captured by accounting for the relaxation of the
      polymer chain and the viscoelastic environment. We show that the ratio of the
      mean displacement to the variance of the displacement during segregation events
      is a critical metric that eliminates the compounding effects of polymer and
      medium dynamics and provides the segregation force. We calculate the force of
      oriC segregation in E. coli to be ~0.49 pN. 

PMID- 25564862
TI  - Subdomain interactions foster the design of two protein pairs with ~80% sequence
      identity but different folds.
AB  - Metamorphic proteins, including proteins with high levels of sequence identity
      but different folds, are exceptions to the long-standing rule-of-thumb that
      proteins with as little as 30% sequence identity adopt the same fold. Which
      topologies can be bridged by these highly identical sequences remains an open
      question. Here we bridge two 3-alpha-helix bundle proteins with two radically
      different folds. Using a straightforward approach, we engineered the sequences of
      one subdomain within maltose binding protein (MBP, alpha/beta/alpha-sandwich) and
      another within outer surface protein A (OspA, beta-sheet) to have high sequence
      identity (80 and 77%, respectively) with engineered variants of protein G (GA, 3
      alpha-helix bundle). Circular dichroism and nuclear magnetic resonance spectra of
      all engineered variants demonstrate that they maintain their native conformations
      despite substantial sequence modification. Furthermore, the MBP variant (80%
      identical to GA) remained active. Thermodynamic analysis of numerous GA and MBP
      variants suggests that the key to our approach involved stabilizing the modified
      MBP and OspA subdomains via external interactions with neighboring substructures,
      indicating that subdomain interactions can stabilize alternative folds over a
      broad range of sequence variation. These findings suggest that it is possible to
      bridge one fold with many other topologies, which has implications for protein
      folding, evolution, and misfolding diseases. 

PMID- 25564863
TI  - From metabolomics to fluxomics: a computational procedure to translate metabolite
      profiles into metabolic fluxes.
AB  - We describe a believed-novel procedure for translating metabolite profiles
      (metabolome) into the set of metabolic fluxes (fluxome) from which they
      originated. Methodologically, computational modeling is integrated with an
      analytical platform comprising linear optimization, continuation and dynamic
      analyses, and metabolic control. The procedure was tested with metabolite
      profiles obtained from ex vivo mice Langendorff-heart preparations perfused with
      glucose. The metabolic profiles were analyzed using a detailed kinetic model of
      the glucose catabolic pathways including glycolysis, pentose phosphate (PP),
      glycogenolysis, and polyols to translate the glucose metabolome of the heart into
      the fluxome. After optimization, the ability of the model to simulate the initial
      metabolite profile was confirmed, and metabolic fluxes as well as the structure
      of control and regulation of the glucose catabolic network could be calculated.
      We show that the step catalyzed by phosphofructokinase together with ATP demand
      and glycogenolysis exert the highest control on the glycolytic flux. The negative
      flux control exerted by phosphofructokinase on the PP and polyol pathways
      revealed that the extent of glycolytic flux directly affects flux redirection
      through these pathways, i.e., the higher the glycolytic flux the lower the PP and
      polyols. This believed-novel methodological approach represents a step forward
      that may help in designing therapeutic strategies targeted to diagnose, prevent,
      and treat metabolic diseases. 

PMID- 25564864
TI  - Elastic behavior and platelet retraction in low- and high-density fibrin gels.
AB  - Fibrin is a biopolymer that gives thrombi the mechanical strength to withstand
      the forces imparted on them by blood flow. Importantly, fibrin is highly
      extensible, but strain hardens at low deformation rates. The density of fibrin in
      clots, especially arterial clots, is higher than that in gels made at plasma
      concentrations of fibrinogen (3-10 mg/mL), where most rheology studies have been
      conducted. Our objective in this study was to measure and characterize the
      elastic regimes of low (3-10 mg/mL) and high (30-100 mg/mL) density fibrin gels
      using shear and extensional rheology. Confocal microscopy of the gels shows that
      fiber density increases with fibrinogen concentration. At low strains, fibrin
      gels act as thermal networks independent of fibrinogen concentration. Within the
      low-strain regime, one can predict the mesh size of fibrin gels by the elastic
      modulus using semiflexible polymer theory. Significantly, this provides a link
      between gel mechanics and interstitial fluid flow. At moderate strains, we find
      that low-density fibrin gels act as nonaffine mechanical networks and transition
      to affine mechanical networks with increasing strains within the moderate regime,
      whereas high-density fibrin gels only act as affine mechanical networks. At high
      strains, the backbone of individual fibrin fibers stretches for all fibrin gels.
      Platelets can retract low-density gels by >80% of their initial volumes, but
      retraction is attenuated in high-density fibrin gels and with decreasing platelet
      density. Taken together, these results show that the nature of fibrin deformation
      is a strong function of fibrin fiber density, which has ramifications for the
      growth, embolization, and lysis of thrombi.

PMID- 25564865
TI  - Noise and low-level dynamics can coordinate multicomponent bet hedging
      mechanisms.
AB  - To counter future uncertainty, cells can stochastically express stress response
      mechanisms to diversify their population and hedge against stress. This approach
      allows a small subset of the population to survive without the prohibitive cost
      of constantly expressing resistance machinery at the population level. However,
      expression of multiple genes in concert is often needed to ensure survival,
      requiring coordination of infrequent events across many downstream targets. This
      raises the question of how cells orchestrate the timing of multiple rare events
      without adding cost. To investigate this, we used a stochastic model to study
      regulation of downstream target genes by a transcription factor. We compared
      several upstream regulator profiles, including constant expression, pulsatile
      dynamics, and noisy expression. We found that pulsatile dynamics and noise are
      sufficient to coordinate expression of multiple downstream genes. Notably, this
      is true even when fluctuations in the upstream regulator are far below the
      dissociation constants of the regulated genes, as with infrequently activated
      genes. As an example, we simulated the dynamics of the multiple antibiotic
      resistance activator (MarA) and 40 diverse downstream genes it regulates,
      determining that low-level dynamics in MarA are sufficient to coordinate
      expression of resistance mechanisms. We also demonstrated that noise can play a
      similar coordinating role. Importantly, we found that these benefits are present
      without a corresponding increase in the population-level cost. Therefore, our
      model suggests that low-level dynamics or noise in a transcription factor can
      coordinate expression of multiple stress response mechanisms by engaging them
      simultaneously without adding to the overall cost. 

PMID- 25564866
TI  - Synonymous mutations reduce genome compactness in icosahedral ssRNA viruses.
AB  - Recent studies have shown that single-stranded (ss) viral RNAs fold into more
      compact structures than random RNA sequences with similar chemical composition
      and identical length. Based on this comparison, it has been suggested that wild
      type viral RNA may have evolved to be atypically compact so as to aid its
      encapsidation and assist the viral assembly process. To further explore the
      compactness selection hypothesis, we systematically compare the predicted sizes
      of >100 wild-type viral sequences with those of their mutants, which are evolved
      in silico and subject to a number of known evolutionary constraints. In
      particular, we enforce mutation synonynimity, preserve the codon-bias, and leave
      untranslated regions intact. It is found that progressive accumulation of these
      restricted mutations still suffices to completely erase the characteristic
      compactness imprint of the viral RNA genomes, making them in this respect
      physically indistinguishable from randomly shuffled RNAs. This shows that
      maintaining the physical compactness of the genome is indeed a primary factor
      among ssRNA viruses' evolutionary constraints, contributing also to the evidence
      that synonymous mutations in viral ssRNA genomes are not strictly neutral.

PMID- 25564867
TI  - Modified protein expression in the tectorial membrane of the cochlea reveals
      roles for the striated sheet matrix.
AB  - The tectorial membrane (TM) of the mammalian cochlea is a complex extracellular
      matrix which, in response to acoustic stimulation, displaces the hair bundles of
      outer hair cells (OHCs), thereby initiating sensory transduction and
      amplification. Here, using TM segments from the basal, high-frequency region of
      the cochleae of genetically modified mice (including models of human hereditary
      deafness) with missing or modified TM proteins, we demonstrate that frequency
      dependent stiffening is associated with the striated sheet matrix (SSM).
      Frequency-dependent stiffening largely disappeared in all three TM mutations
      studied where the SSM was absent either entirely or at least from the stiffest
      part of the TM overlying the OHCs. In all three TM mutations, dissipation of
      energy is decreased at low (<8 kHz) and increased at high (>8 kHz) stimulus
      frequencies. The SSM is composed of polypeptides carrying fixed charges, and
      electrostatic interaction between them may account for frequency-dependent
      stiffness changes in the material properties of the TM. Through comparison with
      previous in vivo measurements, it is proposed that implementation of frequency
      dependent stiffening of the TM in the OHC attachment region facilitates
      interaction among tones, backward transmission of energy, and amplification in
      the cochlea. 

PMID- 25564870
TI  - The adsorption of Pb2+ and Cu2+ onto gum ghatti-grafted poly(acrylamide-co
      acrylonitrile) biodegradable hydrogel: isotherms and kinetic models.
AB  - A biodegradable hydrogel polymer of gum ghatti (Gg) with a copolymer mixture of
      acrylamide (AAm) and acrylonitrile (AN) was synthesized using the free-radical
      graft copolymerization technique. The effect of graft copolymerization on the
      surface area of Gg was studied using BET analyses. The graft copolymerization of
      Gg with poly(AAm-co-AN) was characterized using Fourier transform infrared
      spectroscopy, CHN analysis, thermogravimetric analysis, atomic force microscopy,
      and scanning electron microscopy. The adsorption of Pb(2+) and Cu(2+) from
      aqueous solution using the Gg-cl-P(AAm-co-AN) hydrogel polymer was studied in
      batch mode. The adsorption process was found to be highly pH dependent, and the
      maximum adsorption efficiency was observed at pH 5.0 for both metal ions. The
      adsorption isotherm data were analyzed by applying five different isotherm
      models, namely, the Langmuir, Freundlich, Temkin, Flory-Huggins, and Dubinin
      Kaganer-Radushkevich isothermal models. The Langmuir model was found to fit well
      with the experimental isotherm data, with a maximum adsorption capacity of 384.6
      and 203.7 mg/g for Pb(2+) and Cu(2+), respectively. The metal ion-adsorption
      process was found to be controlled by the pseudo-second-order rate model. The Gg
      cl-P(AAm-co-AN) hydrogel polymer retained its original adsorption capacity for
      three successive cycles of adsorption-desorption. In summary, the potential for
      remediating industrial wastewater polluted by metal ions using the biodegradable
      Gg-cl-P(AAm-co-AN) hydrogel polymer has been demonstrated. 

PMID- 25564871
TI  - Quantifying bulk and surface recombination processes in nanostructured water
      splitting photocatalysts via in situ ultrafast spectroscopy.
AB  - A quantitative description of recombination processes in nanostructured
      semiconductor photocatalysts-one that distinguishes between bulk (charge
      transport) and surface (chemical reaction) losses-is critical for advancing solar
      to-fuel technologies. Here we present an in situ experimental framework that
      determines the bias-dependent quantum yield for ultrafast carrier transport to
      the reactive interface. This is achieved by simultaneously measuring the
      electrical characteristics and the subpicosecond charge dynamics of a
      heterostructured photoanode in a working photoelectrochemical cell. Together with
      direct measurements of the overall incident-photon-to-current efficiency, we
      illustrate how subtle structural modifications that are not perceivable by
      conventional X-ray diffraction can drastically affect the overall photocatalytic
      quantum yield. We reveal how charge carrier recombination losses occurring on
      ultrafast time scales can limit the overall efficiency even in nanostructures
      with dimensions smaller than the minority carrier diffusion length. This is
      particularly true for materials with high carrier concentration, where losses as
      high as 37% are observed. Our methodology provides a means of evaluating the
      efficacy of multifunctional designs where high overall efficiency is achieved by
      maximizing surface transport yield to near unity and utilizing surface layers
      with enhanced activity. 

PMID- 25564869
TI  - Inhibition of succinate dehydrogenase by the mitochondrial chaperone TRAP1 has
      anti-oxidant and anti-apoptotic effects on tumor cells.
AB  - TRAP1 is a mitochondrial chaperone highly expressed in many tumor types; it
      inhibits respiratory complex II, down-modulating its succinate dehydrogenase
      (SDH) enzymatic activity. SDH inhibition in turn leads to a pseudohypoxic state
      caused by succinate-dependent HIF1alpha stabilization and promotes neoplastic
      growth. Here we report that TRAP1 inhibition of SDH also shields cells from
      oxidative insults and from the ensuing lethal opening of the mitochondrial
      permeability transition pore. This anti-oxidant activity of TRAP1 protects tumor
      cells from death in conditions of nutrient paucity that mimic those encountered
      in the neoplasm during the process of malignant accrual, and it is required for
      in vitro tumorigenic growth. Our findings demonstrate that SDH inhibition by
      TRAP1 is oncogenic not only by inducing pseudohypoxia, but also by protecting
      tumor cells from oxidative stress. 

PMID- 25564872
TI  - New insights in amyloid beta interactions with human telomerase.
AB  - It is well-known that aging is the most risk factor for Alzheimer's disease (AD).
      Recent studies have demonstrated that human telomerase is associated with
      pathological mechanisms of AD. In view of the central role of telomere and
      telomerase in the aging process, herein we found that the aggregated form Abeta
      (Abeta1-40 and Abeta1-42), not Abeta monomer, could inhibit telomerase activity
      both in vitro and in living cells. The beta-sheet structures were essential for
      Abeta-induced telomerase inhibition. Further studies indicated Abeta oligomers
      inhibited telomerase activity through binding to DNA.RNA hybrid formed by
      telomeric DNA and the RNA template of telomerase, then blocking telomerase
      elongation of telomeric DNA. We also identified that intracellular Abeta
      localized at telomere, and induced cell senescence and telomere shortening. These
      results indicate that Abeta oligomers can be potential natural inhibitors of
      telomerase and that inhibition of telomerase activity may be one of the factors
      for Abeta-induced cytotoxicity. Our work may offer a new clue to a better
      understanding of aging and AD. 

PMID- 25564868
TI  - Multiscale model of dynamic neuromodulation integrating neuropeptide-induced
      signaling pathway activity with membrane electrophysiology.
AB  - We developed a multiscale model to bridge neuropeptide receptor-activated
      signaling pathway activity with membrane electrophysiology. Typically, the
      neuromodulation of biochemical signaling and biophysics have been investigated
      separately in modeling studies. We studied the effects of Angiotensin II (AngII)
      on neuronal excitability changes mediated by signaling dynamics and downstream
      phosphorylation of ion channels. Experiments have shown that AngII binding to the
      AngII receptor type-1 elicits baseline-dependent regulation of cytosolic Ca(2+)
      signaling. Our model simulations revealed a baseline Ca(2+)-dependent response to
      AngII receptor type-1 activation by AngII. Consistent with experimental
      observations, AngII evoked a rise in Ca(2+) when starting at a low baseline
      Ca(2+) level, and a decrease in Ca(2+) when starting at a higher baseline. Our
      analysis predicted that the kinetics of Ca(2+) transport into the endoplasmic
      reticulum play a critical role in shaping the Ca(2+) response. The Ca(2+)
      baseline also influenced the AngII-induced excitability changes such that lower
      Ca(2+) levels were associated with a larger firing rate increase. We examined the
      relative contributions of signaling kinases protein kinase C and
      Ca(2+)/Calmodulin-dependent protein kinase II to AngII-mediated excitability
      changes by simulating activity blockade individually and in combination. We found
      that protein kinase C selectively controlled firing rate adaptation whereas
      Ca(2+)/Calmodulin-dependent protein kinase II induced a delayed effect on the
      firing rate increase. We tested whether signaling kinetics were necessary for the
      dynamic effects of AngII on excitability by simulating three scenarios of AngII
      mediated KDR channel phosphorylation: (1), an increased steady state; (2), a step
      change increase; and (3), dynamic modulation. Our results revealed that the
      kinetics emerging from neuromodulatory activation of the signaling network were
      required to account for the dynamical changes in excitability. In summary, our
      integrated multiscale model provides, to our knowledge, a new approach for
      quantitative investigation of neuromodulatory effects on signaling and
      electrophysiology. 

PMID- 25564873
TI  - Regiodivergent halogenation of vinylogous esters: one-pot, transition-metal-free
      access to differentiated haloresorcinols.
AB  - We report an efficient method for the regiodivergent synthesis of halogenated
      resorcinol derivatives using readily available vinylogous esters and sulfonyl
      halide halogen donors. Either the 4- or 6-haloresorcinol isomer is accessible
      from a common precursor. In contrast to conventional oxidants for arene
      halogenation, mild sulfonyl halides allow broad functional group compatibility.
      The strategy inherently differentiates the two resorcinol oxygen atoms and
      enhances the potential for complex molecule synthesis. 

PMID- 25564874
TI  - Possible Chemical Source of Discrepancy between in Vitro and in Vivo Tests in
      Nanotoxicology Caused by Strong Adsorption of Buffer Components.
AB  - In the course of studies of the interaction of proteins with TiO2 nanoparticles,
      we have investigated the role of the medium employed in cellular tests, by
      measuring the variation of zeta-potential vs pH in the range 2-9 and bovine serum
      albumin adsorption on TiO2 P25 in the presence of either HEPES or PBS as buffers,
      both mimicking the physiological pH, but with different chemical nature. The two
      buffers yield remarkably dissimilar surface charges and protein uptake, i.e.,
      they impart different surface characteristics to the particles which could affect
      the contact with cells or tissues. This may account for dissimilar toxicological
      outcomes among in vitro tests and particularly between in vitro vs in vivo tests,
      considering the high amount of phosphate ions present in body fluids.

PMID- 25564875
TI  - Ultraviolet light stable and transparent sol-gel methyl siloxane hybrid material
      for UV light-emitting diode (UV LED) encapsulant.
AB  - An ultraviolet (UV) transparent and stable methyl-siloxane hybrid material was
      prepared by a facile sol-gel method. The transparency and stability of a UV-LED
      encapsulant is an important issue because it affects UV light extraction
      efficiency and long-term reliability. We introduced a novel concept for UV-LED
      encapsulation using a thermally curable oligosiloxane resin. The encapsulant was
      fabricated by a hydrosilylation of hydrogen-methyl oligosiloxane resin and vinyl
      methyl siloxane resin, and showed a comparable transmittance to
      polydimethylsiloxane (PDMS) in the UVB (~300 nm) region. Most remarkably, the
      methyl-siloxane hybrid materials exhibited long-term UV stability under light
      soaking in UVB (~300 nm) for 1000 h. 

PMID- 25564877
TI  - Influence of active layer and support layer surface structures on organic fouling
      propensity of thin-film composite forward osmosis membranes.
AB  - In this study, we investigate the influence of surface structure on the fouling
      propensity of thin-film composite (TFC) forward osmosis (FO) membranes.
      Specifically, we compare membranes fabricated through identical procedures except
      for the use of different solvents (dimethylformamide, DMF and N-methyl-2
      pyrrolidinone, NMP) during phase separation. FO fouling experiments were carried
      out with a feed solution containing a model organic foulant. The TFC membranes
      fabricated using NMP (NMP-TFC) had significantly less flux decline (7.47 +/-
      0.15%) when compared to the membranes fabricated using DMF (DMF-TFC, 12.70 +/-
      2.62% flux decline). Water flux was also more easily recovered through physical
      cleaning for the NMP-TFC membrane. To determine the fundamental cause of these
      differences in fouling propensity, the active and support layers of the membranes
      were extensively characterized for physical and chemical characteristics relevant
      to fouling behavior. Polyamide surface roughness was found to dominate all other
      investigated factors in determining the fouling propensities of our membranes
      relative to each other. The high roughness polyamide surface of the DMF-TFC
      membrane was also rich in larger leaf-like structures, whereas the lower
      roughness NMP-TFC membrane polyamide layer contained more nodular and smaller
      features. The support layers of the two membrane types were also characterized
      for their morphological properties, and the relation between support layer
      surface structure and polyamide active layer formation was discussed. Taken
      together, our findings indicate that support layer structure has a significant
      impact on the fouling propensity of the active layer, and this impact should be
      considered in the design of support layer structures for TFC membranes. 

PMID- 25564878
TI  - Polyimide aerogels with amide cross-links: a low cost alternative for
      mechanically strong polymer aerogels.
AB  - Polyimide aerogels combine high porosity, low thermal conductivity, flexibility,
      and low density with excellent mechanical properties. However, previously used
      cross-linkers, such as 1,3,5-triaminophenoxybenzene (TAB), 2,4,6-tris(4
      aminophenyl)pyridine (TAPP), or octa(aminophenoxy)silsesquioxane (OAPS), either
      are not commercially available or are prohibitively expensive. Finding more cost
      efficient cross-linkers that are commercially available to synthesize these
      aerogels is crucial for making large scale manufacturing attractive. Herein, we
      describe an approach to making polyimide aerogels starting with amine capped
      oligomers that are cross-linked with 1,3,5-benzenetricarbonyl trichloride (BTC).
      BTC is a lower cost, commercially available alternative to TAB, TAPP, or OAPS.
      Aerogels made in this way have the same or higher modulus and higher surface area
      compared to those previously reported with either TAB or OAPS cross-links at the
      same density. While the cross-link structure is an amide, the thermal stability
      is not compromised most likely because the cross-link is only a small part of the
      composition of the aerogel. Onset of decomposition depends primarily on the
      backbone chemistry with 4,4'-oxidianiline (ODA) being more thermally stable than
      2,2'-dimethylbenzidine (DMBZ), similar to those previously reported with other
      cross-links. 

PMID- 25564876
TI  - Ecogenomics reveals metals and land-use pressures on microbial communities in the
      waterways of a megacity.
AB  - Networks of engineered waterways are critical in meeting the growing water
      demands in megacities. To capture and treat rainwater in an energy-efficient
      manner, approaches can be developed for such networks that use ecological
      services from microbial communities. Traditionally, engineered waterways were
      regarded as homogeneous systems with little responsiveness of ecological
      communities and ensuing processes. This study provides ecogenomics-derived key
      information to explain the complexity of urban aquatic ecosystems in well-managed
      watersheds with densely interspersed land-use patterns. Overall, sedimentary
      microbial communities had higher richness and evenness compared to the suspended
      communities in water phase. On the basis of PERMANOVA analysis, variation in
      structure and functions of microbial communities over space within same land-use
      type was not significant. In contrast, this difference was significant between
      different land-use types, which had similar chemical profiles. Of the 36
      environmental parameters from spatial analysis, only three metals, namely
      potassium, copper and aluminum significantly explained between 7% and 11% of the
      variation in taxa and functions, based on distance-based linear models (DistLM).
      The ecogenomics approach adopted here allows the identification of key drivers of
      microbial communities and their functions at watershed-scale. These findings can
      be used to enhance microbial services, which are critical to develop ecologically
      friendly waterways in rapidly urbanizing environments. 

PMID- 25564879
TI  - Comment on 'A new method for fusion, denoising and enhancement of x-ray images
      retrieved from Talbot-Lau grating interferometry'.
AB  - In a recent paper (Scholkamm et al 2014 Phys. Med. Biol. 59 1425-40) we presented
      a new image denoising, fusion and enhancement framework for combining and optimal
      visualization of x-ray attenuation contrast, differential phase contrast and dark
      field contrast images retrieved from x-ray Talbot-Lau grating interferometry. In
      this comment we give additional information and report about the application of
      our framework to breast cancer tissue which we presented in our paper as an
      example. The applied procedure is suitable for a qualitative comparison of
      different algorithms. For a quantitative juxtaposition original data would
      however be needed as an input. 

PMID- 25564880
TI  - Association between CARD8 rs2043211 polymorphism and inflammatory bowel disease:
      a meta-analysis.
AB  - OBJECTIVE: The aim of this study was to determine whether caspase recruitment
      domain-containing protein 8 (CARD8) rs2043211 polymorphism was associated with
      susceptibility to inflammatory bowel disease (IBD). METHODS: Relevant studies
      were searched using PubMed and Embase up to February 2014. A meta-analysis was
      conducted on the association between rs2043211 polymorphism and IBD using: (1)
      allele contrast, (2) the dominant model, (3) the recessive model, and (4)
      homozygote contrast. The pooled estimated of risk was obtained by random-effects
      model or fixed-effects model. Publication bias was assessed by Egger's test.
      RESULTS: Eight relevant articles with a total of 10 534 IBD patients [6785
      Crohn's disease (CD), 3713 ulcerative colitis (UC) and 36 indeterminate colitis
      (IC)] and 6755 healthy controls were included in the meta-analysis, which
      consisted of 12 studies, 12 for CD, 10 for UC, 2 for IC. There was no significant
      association between rs2043211 polymorphism and IBD, CD, and IC in overall
      population. However, stratified meta-analysis by ethnicity showed significant
      association between rs2043211 polymorphism and CD in the European population
      under the dominant model [odds ratio (OR) = 1.210, 95% confidence interval (CI) =
      1.013-1.445, p = 0.036] and homozygote contrast (OR = 1.212, 95% CI = 1.005
      1.461, p = 0.044). CONCLUSIONS: Our meta-analysis results indicated significant
      association between rs2043211 polymorphism and the susceptibility to CD under the
      dominant model and homozygote contrast in the European population.

PMID- 25564881
TI  - Favorable effects of low-dose anti-thymocyte globulin in a partially-mismatched
      HLA group in an unrelated allogeneic stem cell transplantation setting.
AB  - BACKGROUND: The outcomes of unrelated stem cell transplantation (SCT) have
      improved with the use of anti-thymocyte globulin (ATG) to prevent graft-versus
      host disease (GVHD) and graft rejection. Therefore, based on the HLA matching
      status classifications of well-matched (WM), partially-matched (PM), and
      mismatched (MM), the current study evaluated the role of ATG use among these 3
      HLA groups in an unrelated SCT setting. MATERIAL AND METHODS: Data from a total
      of 92 patients who received allogeneic SCT from unrelated donors (65 peripheral
      blood and 27 bone marrow) were retrospectively analyzed. RESULTS: Among the 92
      patients, 19 were classified as WM, 42 as PM, and 31 as MM. Fifty-seven patients
      (61.9%) received ATG as GVHD prophylaxis. The overall survival (OS) rate was
      higher for the WM group (83%) when compared to the PM group (54%) and MM group
      (34%, p=0.076). For the PM group, the OS was significantly improved with ATG
      (83.3% vs. 38.6%, p=0.018). However, there was no difference in OS with or
      without ATG for the MM group (32.4% vs. 41.7%, p=0.215). The use of ATG lowered
      the cumulative incidence of grade 3-4 acute GVHD (10% vs. 40.2%, p=0.068) and
      severe chronic GVHD (21.2% vs. 52.2%, p=0.037). CONCLUSIONS: Use of ATG
      effectively improved the survival rate for the PM group in an unrelated SCT
      setting. However, this report has a major limitation in confirming the role of
      ATG for unrelated transplantation because the number of patients in each group
      was too small to compare therapy with ATG and without ATG, and a heterogeneous
      population was included in the current study. A larger study comparing different
      doses of ATG for unrelated PBSCT in a homogenous population will be needed to
      confirm the role of ATG.

PMID- 25564882
TI  - Two-year survival rates of anti-TNF-alpha therapy in psoriatic arthritis (PsA)
      patients with either polyarticular or oligoarticular PsA.
AB  - OBJECTIVES: To evaluate the 2-year drug survival rates of the tumour necrosis
      factor (TNF)-alpha blockers adalimumab, etanercept, and infliximab in psoriatic
      arthritis (PsA) patients with either oligoarticular (oligo-PsA) or polyarticular
      PsA (poly-PsA). METHOD: We studied a prospective cohort of 328 PsA patients with
      peripheral arthritis (213 with poly-PsA and 115 with oligo-PsA), beginning their
      first ever anti-TNF-alpha treatment with adalimumab, etanercept, or infliximab.
      The aim of the study was to evaluate the drug survival rates and possible
      baseline predictors at 2 years. RESULTS: After 24 months, persistence in therapy
      with the first anti-TNF-alpha blocker was not statistically different in the
      oligo-PsA (70.4%) and poly-PsA (65.7%) subsets. Predictors of drug
      discontinuation were female sex [hazard ratio (HR) 1.63, 95% confidence interval
      (CI) 1.00-2.68, p = 0.04] and starting the therapy in years 2003-8 (HR 0.51, 95%
      CI 0.33-0.80, p = 0.003). In poly-PsA, the persistence of etanercept (68.3%) was
      significantly higher than that of adalimumab (51.9%, p = 0.01), whereas in oligo
      PsA no significant difference was detected. In poly-PsA, the period 2003-8 was a
      negative predictor (HR 0.36, 95% CI 0.21-0.62, p = 0.0001) whereas in oligo-PsA
      female gender was a positive predictor of drug discontinuation (HR 2.08, 95% CI
      1.02-4.24, p = 0.04). With regard to clinical outcomes, the best responses in
      terms of European League Against Rheumatism (EULAR) 'good' response or Disease
      Activity Score (DAS28) remission, crude or adjusted according to the LUND
      Efficacy indeX (LUNDEX), were seen in patients on etanercept or infliximab.
      CONCLUSIONS: Our study provides some evidence that anti-TNF-alpha drugs may
      perform differently in PsA, and that the analysis of clinical disease subsets may
      improve our knowledge and promote better management of PsA.

PMID- 25564884
TI  - Correlation between the disc status in MRI and the different types of traumatic
      temporomandibular joint ankylosis.
AB  - OBJECTIVES: We aimed to investigate the correlation between the disc status in
      MRI and the different types of traumatic temporomandibular joint (TMJ) ankylosis.
      METHODS: 51 consecutive patients (69 joints), diagnosed with traumatic TMJ
      ankylosis with a residual condyle (Types A2 and A3), were included in this study.
      All patients had pre-operative MRI, which was reviewed to determine the disc
      shape, length and position. The results were compared using the Mann-Whitney
      test. RESULTS: There were 37 joints of Type A2 ankylosis and 32 joints of Type
      A3. All joints of Type A2 and 27 joints of Type A3 (84.4%) definitely had a
      discernible disc, while 5 joints of Type A3 had no discernible discs. Among the
      discernible discs, the lateral disc of Type A2 and the whole disc of Type A3 had
      severe deformity, while the medial disc of Type A2 had mild deformity. The mean
      (standard deviation) disc length was 10.88 (1.19) mm in Type A2, but 7.50 (0.82)
      mm in Type A3. There was a significant difference between Types A2 and A3 (p <
      0.05). As for the disc position, the intermediate position was found in all
      joints. CONCLUSIONS: There is a correlation between the disc status and the
      different types of traumatic TMJ ankylosis. Therefore, MRI examination is needed
      to help treatment planning and predict post-operative TMJ function.

PMID- 25564883
TI  - Senescence from G2 arrest, revisited.
AB  - Senescence was classically defined as an irreversible cell cycle arrest in G1
      phase (G1 exit) triggered by eroded telomeres in aged primary cells. The
      molecular basis of this G1 arrest is thought to be due to a DNA damage response,
      resulting in accumulation of the cyclin dependent kinase (Cdk) inhibitors p21 and
      p16 that block the inactivating phosphorylation of the retinoblastoma tumor
      suppressor pRb, thereby preventing DNA replication. More than a decade ago,
      several studies showed that p21 also mediates permanent DNA damage-induced cell
      cycle arrest in G2 (G2 exit) by inhibiting mitotic Cdk complexes and pRb
      phosphorylation. The idea that the senescence program can also be launched after
      G2 arrest has gained support from several recent publications, including evidence
      for its existence in vivo.

PMID- 25564885
TI  - Dose reduction in orthodontic lateral cephalography: dosimetric evaluation of a
      novel cephalographic thyroid protector (CTP) and anatomical cranial collimation
      (ACC).
AB  - OBJECTIVES: To test the dose-reducing capabilities of a novel thyroid protection
      device and a recently introduced cranial collimator to be used in orthodontic
      lateral cephalography. METHODS: Cephalographic thyroid protector (CTP) was
      designed to shield the thyroid while leaving the cervical vertebrae depicted.
      Using a RANDO((r)) head phantom (The Phantom Laboratory, Salem, NY) equipped with
      dosemeters and a Proline XC (Planmeca, Helsinki, Finland) cephalograph, lateral
      cephalograms were taken, and the effective dose (ED) was calculated for four
      protocols: (1) without shielding; (2) with CTP; (3) with CTP and anatomical
      cranial collimator (ACC); and (4) with a thyroid collar (TC). RESULTS: The ED for
      the respective protocols was (1) 8.51; (2) 5.39; (3) 3.50; and (4) 4.97 uSv. The
      organ dose for the thyroid was reduced from 30.17 to 4.50 uSv in Protocols 2 and
      3 and to 3.33 uSv in Protocol 4. CONCLUSIONS: The use of just the CTP (Protocol
      2) resulted in a 36.8% reduction of the ED of a lateral cephalogram. This was
      comparable to the classical TC (Protocol 4). A 58.8% reduction of the ED was
      obtained when combining CTP and ACC (Protocol 3). The dose to the radiosensitive
      thyroid gland was reduced by 85% in Protocols 2 and 3 and by 89% in Protocol 4.

PMID- 25564886
TI  - Three-dimensional reconstruction of teeth and jaws based on segmentation of CT
      images using watershed transformation.
AB  - The objective of the present study was the development and clinical testing of a
      three-dimensional (3D) reconstruction method of teeth and a bone tissue of the
      jaw on the basis of CT images of the maxillofacial region. 3D reconstruction was
      performed using the specially designed original software based on watershed
      transformation. Computed tomograms in digital imaging and communications in
      medicine format obtained on multispiral CT and CBCT scanners were used for
      creation of 3D models of teeth and the jaws. The processing algorithm is realized
      in the stepwise threshold image segmentation with the placement of markers in the
      mode of a multiplanar projection in areas relating to the teeth and a bone
      tissue. The developed software initially creates coarse 3D models of the entire
      dentition and the jaw. Then, certain procedures specify the model of the jaw and
      cut the dentition into separate teeth. The proper selection of the segmentation
      threshold is very important for CBCT images having a low contrast and high noise
      level. The developed semi-automatic algorithm of multispiral and cone beam
      computed tomogram processing allows 3D models of teeth to be created separating
      them from a bone tissue of the jaws. The software is easy to install in a
      dentist's workplace, has an intuitive interface and takes little time in
      processing. The obtained 3D models can be used for solving a wide range of
      scientific and clinical tasks. 

PMID- 25564887
TI  - Comparison of mandibular bone microarchitecture between micro-CT and CBCT images.
AB  - OBJECTIVES: To compare microarchitecture parameters of bone samples scanned using
      micro-CT (uCT) to those obtained by using CBCT. METHODS: A bone biopsy trephine
      bur (3 * 10 mm) was used to remove 20 cylindrical bone samples from 20 dry
      hemimandibles. Samples were scanned using uCT (uCT 35; SCANCO Medical,
      Bruttisellen, Switzerland) with a voxel size of 20 um and CBCT (3D Accuitomo 170;
      J. Morita, Kyoto, Japan) with a voxel size of 80 um. All corresponding sample
      scans were aligned and cropped. Image analysis was carried out using BoneJ,
      including the following parameters: skeleton analysis, bone surface per total
      volume (BS/TV), bone volume per total volume (BV/TV), connectivity density,
      anisotropy, trabecular thickness and spacing, structure model index, plateness
      and fractal dimension. Pearson and Spearman correlation coefficients (R) were
      calculated. CBCT values were then calibrated using the slope of the linear fit
      with the uCT values. The mean error after calibration was calculated and
      normalized to the standard deviation of the uCT values. RESULTS: R-values ranged
      between 0.05 (plateness) and 0.83 (BS/TV). Correlation was significant for both
      Spearman and Pearson's R for 8 out of 16 parameters. After calibration, the
      smallest normalized error was found for BV/TV (0.48). For other parameters, the
      error range was 0.58-2.10. CONCLUSIONS: Despite the overall correlation, this
      study demonstrates the uncertainty associated with using bone microarchitecture
      parameters on CBCT images. Although clinically relevant parameter ranges are not
      available, the errors found in this study may be too high for some parameters to
      be considered for clinical application.

PMID- 25564888
TI  - Comparison between DICOM-calibrated and uncalibrated consumer grade and 6-MP
      displays under different lighting conditions in panoramic radiography.
AB  - OBJECTIVES: To compare observer performance in the detection of anatomical
      structures and pathology in panoramic radiographs using consumer grade with and
      without digital imaging and communication in medicine (DICOM)-calibration and 6
      megapixel (6-MP) displays under different lighting conditions. METHODS: 30
      panoramic radiographs were randomly evaluated on three displays under bright (510
      lx) and dim (16 lx) ambient lighting by two observers with different years of
      experience. Dentinoenamel junction, dentinal caries and periapical inflammatory
      lesions, visibility of cortical border of the floor and pathological lesions in
      maxillary sinus were evaluated. Consensus between the observers was considered as
      reference. Intraobserver agreement was determined. Proportion of equivalent
      ratings and weighted kappa were used to assess reliability. The level of
      significance was set to p < 0.05. RESULTS: The proportion of equivalent ratings
      with consensus differed between uncalibrated and DICOM-calibrated consumer grade
      displays in dentinal caries in the lower molar in dim lighting (p = 0.021) and
      between DICOM-calibrated consumer grade and 6-MP display in bright lighting (p =
      0.038) for an experienced observer. Significant differences were found between
      uncalibrated and DICOM-calibrated consumer grade displays in dentinal caries in
      bright lighting (p = 0.044) and periapical lesions in the upper molar in dim
      lighting (p = 0.008) for a less experienced observer. Intraobserver reliability
      was better at detecting dentinal caries than at detecting periapical and
      maxillary sinus pathology. CONCLUSIONS: DICOM calibration may improve observer
      performance in panoramic radiography in different lighting conditions. Therefore,
      a DICOM-calibrated consumer grade display can be used instead of a medical
      display in dental practice without compromising the diagnostic quality.

PMID- 25564889
TI  - Parotid necrotizing sialometaplasia vs infarcted Warthin tumour.

PMID- 25564891
TI  - Angiostrongylus cantonensis in Introduced Gastropods in Southern Florida.
AB  - Angiostrongylus cantonensis , the rat lungworm, is a zoonotic, parasitic nematode
      that uses the rat as a definitive host and gastropods as intermediate hosts. It
      is prevalent in parts of Asia, the Pacific islands, and the Caribbean. In the
      United States, A. cantonensis is established in Hawaii and in recent years has
      been reported in Alabama, California, Louisiana, and Florida, where it has been
      found in the reintroduced Lissachatina fulica (also known as Achatina fulica),
      the giant African snail that was once eradicated from the state. Since 2004, A.
      cantonensis has been identified as the causative agent for 2 non-human primate
      deaths in Florida, one attributed to ingestion of the snail Zachrysia provisoria.
      Our study further supports the presence of A. cantonensis in Z. provisoria in
      Florida and identifies 2 additional introduced terrestrial snails, Bradybaena
      similaris and Alcadia striata, that serve as intermediate hosts for A.
      cantonensis , as well as evidence of rat infection, in southern Florida. The
      finding of both definitive and intermediate hosts suggests that A. cantonensis
      may be established in south Florida. 

PMID- 25564890
TI  - Exploration of depressive symptoms in African American cancer patients.
AB  - BACKGROUND: Accurately assessing depression in African American cancer patients
      is difficult because of the similarities of physical symptoms observed in cancer
      and depression. AIM: To identify universal and distinctive depressive symptoms in
      African American cancer patients. METHODS: Seventy-four cancer patients (34
      depressed and 23 non-depressed African Americans, and 17 depressed Whites) were
      interviewed. Qualitative and quantitative analyses were conducted. RESULTS:
      Compared to non-depressed African Americans, depressed African Americans reported
      irritability, social isolation, insomnia, fatigue and crying (p <= 0.05) more
      frequently over time. Compared to depressed Whites, they reported sadness,
      frustration and intrusive thoughts less frequently (p <= 0.05), but insomnia and
      fatigue more frequently (p <= 0.05) during cancer treatment. There was little
      racial difference at the time of interview. CONCLUSION: Depressed African
      American cancer patients may benefit from more culturally sensitive depression
      measures that consider symptoms of irritability, social isolation and altered
      expressions of depressive mood.

PMID- 25564892
TI  - Overdose Education and Naloxone Rescue Kits for Family Members of Individuals Who
      Use Opioids: Characteristics, Motivations, and Naloxone Use.
AB  - BACKGROUND: In response to the overdose epidemic, a network of support groups for
      family members in Massachusetts has been providing overdose education and
      naloxone rescue kits (OEN). The aims of this study were to describe the
      characteristics, motivations, and benefits of family members who receive OEN and
      to describe the frequency of naloxone used during an overdose rescue. METHODS:
      This cross-sectional, multisite study surveyed attendees of community support
      groups for family members of opioid users where OEN training was offered using a
      42-item self-administered survey that included demographics, relationship to the
      individual using opioids, experience with overdose, motivations to receive OEN,
      and naloxone rescue kit use. RESULTS: Of 126 attendees who completed surveys at 8
      sites, most attendees were white (95%), female (78%), married or partnered (74%),
      parents of an individual using opioids (85%), and providing financial support for
      the individual using opioids (52%). The OEN trainees (79%) were more likely than
      attendees not trained (21%) to be parents of an individual using opioids (91% vs.
      65%, P < .05), to provide financial support to an individual using opioids (58%
      vs. 30%, P < .05), and to have witnessed an overdose (35% vs. 12%, P = .07). The
      major motivations to receive training were wanting a kit in their home (72%),
      education provided at the meeting (60%), and hearing about benefits from others
      (57%). Sixteen parents reported witnessing their child overdose, and 5 attendees
      had used naloxone successfully during an overdose rescue. CONCLUSIONS: Support
      groups for families of people who use opioids are promising venues to conduct
      overdose prevention trainings because attendees are motivated to receive training
      and will use naloxone to rescue people when witnessing an overdose. Further study
      is warranted to understand how to optimize this approach to overdose prevention
      in the community setting.

PMID- 25564893
TI  - The impact of HIV treatment-related stigma on uptake of antiretroviral therapy.
AB  - HIV-related stigma has been linked to avoidance of health care services and
      suboptimal adherence to antiretroviral therapy (ART). However, less is known
      about concerns of stigma related specifically to the taking of ART in uptake of
      treatment. This study examines experiences of HIV treatment-related stigma and
      assesses if these experiences are associated with ART uptake, independent of
      general HIV-related stigma. People living with HIV (PLHIV; n = 697) were targeted
      to complete an online questionnaire measuring perceived HIV- and treatment
      related stigma, social support, self-esteem, resilience, psychological distress,
      health satisfaction and quality of life. Findings suggest that experiences of
      general and treatment-related stigma were common, and that participants appear to
      experience greater stigma related to taking HIV treatment than general stigma
      associated with HIV. Neither general nor treatment-related stigma uniquely
      impacted HIV treatment uptake. Instead, treatment uptake was associated with
      being older (adjusted OR 1.05; 95% CIs: 1.03, 1.08), greater duration of HIV
      infection (adjusted OR 1.07; 95% CIs: 1.03-1.11) and having greater health
      satisfaction (adjusted OR 1.28; 95% CIs: 1.03, 1.59). Findings highlight that
      concerns around taking HIV treatment can be an added source of stigma for PLHIV,
      however other factors may be greater contributors to the likelihood of taking HIV
      treatment. 

PMID- 25564894
TI  - Maintenance of certification 2.0--strong start, continued evolution.

PMID- 25564895
TI  - Boarded to death--why maintenance of certification is bad for doctors and
      patients.

PMID- 25564896
TI  - Beyond a traditional payer--CMS's role in improving population health.

PMID- 25564898
TI  - Clinical practice. Complicated grief.

PMID- 25564899
TI  - Images in clinical medicine. Acute generalized exanthematous pustulosis.

PMID- 25564897
TI  - Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast
      cancer.
AB  - BACKGROUND: No single standard treatment exists for patients with small, node
      negative, human epidermal growth factor receptor type 2 (HER2)-positive breast
      cancers, because most of these patients have been ineligible for the pivotal
      trials of adjuvant trastuzumab. METHODS: We performed an uncontrolled, single
      group, multicenter, investigator-initiated study of adjuvant paclitaxel and
      trastuzumab in 406 patients with tumors measuring up to 3 cm in greatest
      dimension. Patients received weekly treatment with paclitaxel and trastuzumab for
      12 weeks, followed by 9 months of trastuzumab monotherapy. The primary end point
      was survival free from invasive disease. RESULTS: The median follow-up period was
      4.0 years. The 3-year rate of survival free from invasive disease was 98.7% (95%
      confidence interval [CI], 97.6 to 99.8). Among the 12 relapses seen, 2 were due
      to distant metastatic breast cancer. Excluding contralateral HER2-negative breast
      cancers and nonbreast cancers, 7 disease-specific events were noted. A total of
      13 patients (3.2%; 95% CI, 1.7 to 5.4) reported at least one episode of grade 3
      neuropathy, and 2 had symptomatic congestive heart failure (0.5%; 95% CI, 0.1 to
      1.8), both of whom had normalization of the left ventricular ejection fraction
      after discontinuation of trastuzumab. A total of 13 patients had significant
      asymptomatic declines in ejection fraction (3.2%; 95% CI, 1.7 to 5.4), as defined
      by the study, but 11 of these patients were able to resume trastuzumab therapy
      after a brief interruption. CONCLUSIONS: Among women with predominantly stage I
      HER2-positive breast cancer, treatment with adjuvant paclitaxel plus trastuzumab
      was associated with a risk of early recurrence of about 2%; 6% of patients
      withdrew from the study because of protocol-specified adverse events. (Funded by
      Genentech; ClinicalTrials.gov number, NCT00542451.).

PMID- 25564901
TI  - Restoring synaptic connections in the inner ear after noise damage.

PMID- 25564900
TI  - Case records of the Massachusetts General Hospital. Case 1-2015. A 66-year-old
      woman with metastatic breast cancer after endocrine therapy.

PMID- 25564902
TI  - Beyond belief--how people feel about taking medications for heart disease.

PMID- 25564903
TI  - Ebola virus disease in West Africa--the first 9 months.

PMID- 25564904
TI  - Ebola virus disease in West Africa--the first 9 months.

PMID- 25564905
TI  - Ebola virus disease in West Africa--the first 9 months.

PMID- 25564906
TI  - Goal-directed resuscitation in septic shock.

PMID- 25564907
TI  - Goal-directed resuscitation in septic shock.

PMID- 25564908
TI  - Goal-directed resuscitation in septic shock.

PMID- 25564909
TI  - Goal-directed resuscitation in septic shock.

PMID- 25564910
TI  - The effect of malpractice reform on emergency department care.

PMID- 25564911
TI  - The effect of malpractice reform on emergency department care.

PMID- 25564912
TI  - The effect of malpractice reform on emergency department care.

PMID- 25564913
TI  - Physiological approach to assessment of acid-base disturbances.

PMID- 25564914
TI  - Physiological approach to assessment of acid-base disturbances.

PMID- 25564915
TI  - Physiological approach to assessment of acid-base disturbances.

PMID- 25564916
TI  - Physiological approach to assessment of acid-base disturbances.

PMID- 25564917
TI  - Physiological approach to assessment of acid-base disturbances.

PMID- 25564918
TI  - Inefficacy of platelet transfusion to reverse ticagrelor.

PMID- 25564921
TI  - Images in clinical medicine. Kussmaul's sign.

PMID- 25564923
TI  - Validation of good agricultural practices (GAP) on Minnesota vegetable farms.
AB  - The United States Food and Drug Administration and the Department of Agriculture
      jointly published the "Guide to Minimize Microbial Food Safety Hazards for Fresh
      Fruits and Vegetables," which is used as a basis for Good Agricultural Practices
      (GAP) audits. To understand barriers to incorporation of GAP by Minnesota
      vegetable farmers, a mail survey completed in 2008 was validated with visits to a
      subset of the farms. This was done to determine the extent to which actual
      practices matched perceived practices. Two hundred forty-six producers completed
      the mail survey, and 27 participated in the on-farm survey. Over 75% of the on
      farm survey respondents produced vegetables on 10 acres or less and had 10 or
      fewer employees. Of 14 questions, excellent agreement between on-farm interviews
      and mail survey responses was observed on two questions, four questions had poor
      or slight agreement, and eight questions had no agreement. Ninety-two percent of
      respondents by mail said "they took measures to keep animals and pests out of
      packing and storage buildings." However, with the on-site visit only 45% met this
      requirement. Similarly, 81% of respondents by mail said "measures were taken to
      reduce the risk of wild and/or domestic animals entering into fruit and vegetable
      growing areas." With direct observation, 70% of farms actually had taken measures
      to keep animals out of the growing areas. Additional, on-farm assessments were
      done regarding employee hygiene, training, presence of animals, water sources,
      and composting practices. This validation study demonstrated the challenge of
      creating nonleading and concise questions that are not open to broad
      interpretation from the respondents. If mail surveys are used to assess GAP, they
      should include open-ended questions and ranking systems to better assess farm
      practices. To provide the most accurate survey data for educational purposes or
      GAP audits, on-farm visits are recommended. 

PMID- 25564922
TI  - Multiscale modeling of four-component lipid mixtures: domain composition, size,
      alignment, and properties of the phase interface.
AB  - Simplified lipid mixtures are often used to model the complex behavior of the
      cell plasma membrane. Indeed, as few as four components-a high-melting lipid, a
      nandomain-inducing low-melting lipid, a macrodomain-inducing low-melting lipid,
      and cholesterol (chol)-can give rise to a wide range of domain sizes and patterns
      that are highly sensitive to lipid compositions. Although these systems are
      studied extensively with experiments, the molecular-level details governing their
      phase behavior are not yet known. We address this issue by using molecular
      dynamics simulations to analyze how phase separation evolves in a four-component
      system as it transitions from small domains to large domains. To do so, we fix
      concentrations of the high-melting lipid 16:0,16:0-phosphatidylcholine (DPPC) and
      chol, and incrementally replace the nanodomain-inducing low-melting lipid
      16:0,18:2-PC (PUPC) by the macrodomain-inducing low-melting lipid 18:2,18:2-PC
      (DUPC). Coarse-grained simulations of this four-component system reveal that
      lipid demixing increases as the amount of DUPC increases. Additionally, we find
      that domain size and interleaflet alignment change sharply over a narrow range of
      replacement of PUPC by DUPC, indicating that intraleaflet and interleaflet
      behaviors are coupled. Corresponding united atom simulations show that only
      lipids within ~2 nm of the phase interface are significantly perturbed regardless
      of domain composition or size. Thus, whereas the fraction of interface-perturbed
      lipids is negligible for large domains, it is significant for smaller ones.
      Together, these results reveal characteristic traits of bilayer thermodynamic
      behavior in four-component mixtures, and provide a baseline for investigation of
      the effects of proteins and other lipids on membrane phase properties. 

PMID- 25564924
TI  - Humidity effect on nanoscale electrochemistry in solid silver ion conductors and
      the dual nature of its locality.
AB  - Scanning probe microscopy (SPM) is a powerful tool to investigate
      electrochemistry in nanoscale volumes. While most SPM-based studies have focused
      on reactions at the tip-surface junction, charge and mass conservation requires
      coupled and intrinsically nonlocal cathodic and anodic processes that can be
      significantly affected by ambient humidity. Here, we explore the role of water in
      both cathodic and anodic processes, associated charge transport, and topographic
      volume changes depending on the polarity of tip bias. The first-order reversal
      curve current-voltage technique combined with simultaneous detection of the
      sample topography, referred to as FORC-IVz, was applied to a silver solid ion
      conductor. We found that the protons generated from water affect silver ionic
      conduction, silver particle formation and dissolution, and mechanical integrity
      of the material. This work highlights the dual nature (simultaneously local and
      nonlocal) of electrochemical SPM studies, which should be considered for
      comprehensive understanding of nanoscale electrochemistry. 

PMID- 25564927
TI  - Land degradation research: the need for a broader focus.

PMID- 25564926
TI  - The PrOSTE: identifying key components of effective procedural teaching.
AB  - RATIONALE: Novel approaches for faculty development and assessment of procedural
      teaching skills are needed to improve the procedural education of trainees. The
      Objective Structured Teaching Exercise (OSTE) entails a simulated encounter in
      which faculty are observed teaching a standardized student and has been used to
      evaluate teaching skills. Use of an OSTE to assess the teaching of central venous
      catheterization has not been reported. OBJECTIVES: The purpose of this study was
      to develop a procedural OSTE for subclavian central venous catheter (CVC)
      insertion and to determine specific aspects of procedural teaching associated
      with improved skills in novices. METHODS: Critical care faculty/fellows taught a
      standardized student to insert a CVC in a simulator. We assessed the instructor's
      teaching skills using rating scales to generate a procedural teaching score.
      After this encounter, the instructor taught novice medical students to place CVCs
      in simulators. Novices then independently placed catheters in simulators and were
      evaluated by trained observers using a checklist. Generalized estimating
      equations were used to examine the correlation between specific teaching
      behaviors and the novices' skills in CVC placement. MEASUREMENTS AND MAIN
      RESULTS: We recruited 10 participants to serve as teachers and 30 preclinical
      medical students to serve as novice learners. The overall mean procedural
      teaching score was 85.5 (+/-15.4). Improved student performance was directly
      related to the degree to which the teacher "provided positive feedback" (beta =
      1.53, SE = 0.44, P = 0.001), "offered learner suggestions for improvement" (beta
      = 1.40, SE = 0.35, P < 0.001), and "demonstrated the procedure in a step-by-step
      manner" (beta = 2.50, SE = 0.45, P < 0.001). There was no significant correlation
      between total scores and student skills (beta = 0.06, SE = 0.46, P = 0.18).
      CONCLUSIONS: The OSTE is a standardized method to assess procedural teaching
      skills. Our findings suggest that specific aspects of procedural teaching should
      be emphasized to ensure effective transfer of psychomotor skills to trainees.

PMID- 25564925
TI  - Gender, diabetes education, and psychosocial factors are associated with
      persistent poor glycemic control in patients with type 2 diabetes in the Joint
      Asia Diabetes Evaluation (JADE) program.
AB  - BACKGROUND: Factors associated with persistent poor glycemic control were
      explored in patients with type 2 diabetes under the Joint Asia Diabetes
      Evaluation (JADE) program. METHODS: Chinese adults enrolled in JADE with HbA1c
      >=8% at initial comprehensive assessment (CA1) and repeat assessment were
      analyzed. The improved group was defined as those with a >=1% absolute reduction
      in HbA1c, and the unimproved group was those with <1% reduction at the repeat CA
      (CA2). RESULTS: Of 4458 enrolled patients with HbA1c >=8% at baseline, 1450
      underwent repeat CA. After a median interval of 1.7 years (interquartile
      range[IQR] 1.1-2.2) between CA1 and CA2, the unimproved group (n = 677) had a
      mean 0.4% (95% confidence interval [CI] 0.3%, 0.5%) increase in HbA1c compared
      with a mean 2.8% reduction (95% CI -2.9, -2.6%) in the improved group (n = 773).
      The unimproved group had a female preponderance with lower education level, and
      was more likely to be insulin treated. Patients in the improved group received
      more diabetes education between CAs with improved self-care behaviors, whereas
      the unimproved group had worsening of health-related quality of life at CA2.
      Apart from female gender, long disease duration, low educational level, obesity,
      retinopathy, history of hypoglycemia, and insulin use, lack of education from
      diabetes nurses between CAs had the strongest association for persistent poor
      glycemic control. CONCLUSIONS: These results highlight the multidimensional
      nature of glycemic control, and the importance of diabetes education and
      optimizing diabetes care by considering psychosocial factors.

PMID- 25564928
TI  - Mechanism of H2O insertion and chemical bond formation in AlPO(4)-54.xH2O at high
      pressure.
AB  - The insertion of H2O in AlPO4-54.xH2O at high pressure was investigated by single
      crystal X-ray diffraction and Monte Carlo molecular simulation. H2O molecules are
      concentrated, in particular, near the pore walls. Upon insertion, the additional
      water is highly disordered. Insertion of H2O (superhydration) is found to impede
      pore collapse in the material, thereby strongly modifying its mechanical
      behavior. However, instead of stabilizing the structure with respect to
      amorphization, the results provide evidence for the early stages of chemical bond
      formation between H2O molecules and tetrahedrally coordinated aluminum, which is
      at the origin of the amorphization/reaction process. 

PMID- 25564929
TI  - The role of biventricular pacing in the prevention and therapy of pacemaker
      induced cardiomyopathy.
AB  - Right ventricular (RV) pacing produces well-known long-term deleterious effects
      not only on already compromised, but also on the normal left ventricle (LV). The
      activation pattern mimicks that of left bundle branch block, with delayed
      activation of the LV free wall, and results in electrical and mechanical
      dyssynchrony. Long-term mandatory (100%) RV pacing, increases LV dimensions and
      decreases the ejection fraction. Many of these negative effects of pacing can be
      overcome by biventricular pacing. In this review, we describe the characteristics
      of pacemaker-induced cardiomyopathy, its incidence, and the use of cardiac
      resynchronization therapy (CRT) for its therapy and prevention. The gaps in the
      current organizational guidelines for using CRT in the treatment of bradycardia
      are identified, and goals for future research are discussed. 

PMID- 25564930
TI  - Ring contraction of 2,5-dihydrobenzo[f][1,2,5]thiadiazepine 1,1-dioxides: access
      to 4H-benzo[b][1,4]thiazine 1,1-dioxides.
AB  - We report an efficient synthesis of 4H-benzo[b][1,4]thiazine 1,1-dioxides via
      unprecedented ring contraction of 2,5-dihydrobenzo[f][1,2,5]thiadiazepine 1,1
      dioxides under mild conditions involving carbon-sulfur bond formation. 2,5
      Dihydrobenzo[f][1,2,5]thiadiazepine 1,1-dioxides are easily accessible from
      commercially available building blocks, including Fmoc-protected amino acids, 2
      nitrobenzenesulfonyl chlorides, and bromo ketones. Benzothiazine 1,1-dioxides
      represent pharmacologically relevant derivatives with biological, medicinal, and
      industrial applications. 

PMID- 25564931
TI  - Transitions and tensions: the discipline of nursing in an interdisciplinary
      context.

PMID- 25564933
TI  - States of consciousness: new insights and further questions.

PMID- 25564932
TI  - Effects of the demographic transition on the genetic variances and covariances of
      human life-history traits.
AB  - The recent demographic transitions to lower mortality and fertility rates in most
      human societies have led to changes and even quick reversals in phenotypic
      selection pressures. This can only result in evolutionary change if the affected
      traits are heritable, but changes in environmental conditions may also lead to
      subsequent changes in the genetic variance and covariance (the G matrix) of
      traits. It currently remains unclear if there have been concomitant changes in
      the G matrix of life-history traits following the demographic transition. Using
      300 years of genealogical data from Finland, we found that four key life-history
      traits were heritable both before and after the demographic transition. The
      estimated heritabilities allow a quantifiable genetic response to selection
      during both time periods, thus facilitating continued evolutionary change.
      Further, the G matrices remained largely stable but revealed a trend for an
      increased additive genetic variance and thus evolutionary potential of the
      population after the transition. Our results demonstrate the validity of
      predictions of evolutionary change in human populations even after the recent
      dramatic environmental change, and facilitate predictions of how our biology
      interacts with changing environments, with implications for global public health
      and demography. 

PMID- 25564934
TI  - Dr Hilary Hart: Lector, si monumentum requiris, circumspice.

PMID- 25564935
TI  - Quality of supervision: postgraduate dental research trainees' perspectives.
AB  - INTRODUCTION: Supervision is a pillar in enhancing the student's learning
      environment throughout her/his higher education. Multiple studies qualify
      graduate supervision among the most important contributors to the successful
      completion of a higher education degree and to graduate students' positive
      academic experience. The aim of this study was to assess the views of graduate
      students enrolled in the Dental Sciences and Craniofacial Research Graduate
      Programs at McGill University (n = 64) regarding the quality of supervision they
      are receiving. METHODS AND MATERIALS: An online questionnaire composed of 22 open
      and closed-ended format items was used and covered five domains: student profile,
      supervisory relationship, conflict resolution, student progress/thesis writing
      and career development. Descriptive statistics, chi-square tests and
      interpretative qualitative analysis were used to evaluate students' perspectives.
      RESULTS: Fifty-nine students completed the survey (92.2%). The distribution of
      sample in regard to the graduate student level was almost identical (M.Sc. level
      n = 28, Ph.D. n = 31). Overall, most graduate students appeared satisfied with
      the supervision they received and had similar perspectives about the surveyed
      domains. There was one statistically significant difference (P < 0.05) between
      MSc and PhD students when asked if their supervisors aided them in career
      development outside the supervisory relationship, where 77.4% (n = 24) of
      doctoral students agreed as opposed to 21.4% (n = 12) of Masters' students.
      CONCLUSIONS: Our results showed that McGill graduate students appeared to be
      overall satisfied with the supervision they received. The main elements
      contributing to a positive supervision experience were support, guidance,
      availability and good communication between supervisees and supervisors.

PMID- 25564936
TI  - Sound the Alarm: The Effect of Narcissism on Retaliatory Aggression Is Moderated
      by dACC Reactivity to Rejection.
AB  - Narcissists behave aggressively when their egos are threatened by interpersonal
      insults. This effect has been explained in terms of narcissists' motivation to
      reduce the discrepancy between their grandiose self and its threatened version,
      though no research has directly tested this hypothesis. If this notion is true,
      the link between narcissism and retaliatory aggression should be moderated by
      neural structures that subserve discrepancy detection, such as the dorsal
      anterior cingulate cortex (dACC). This study tested the hypothesis that
      narcissism would only predict greater retaliatory aggression in response to
      social rejection when the dACC was recruited by the threat. Thirty participants
      (15 females; Mage  = 18.86, SD = 1.25; 77% White) completed a trait narcissism
      inventory, were socially accepted and then rejected while undergoing fMRI, and
      then could behave aggressively toward one of the rejecters by blasting him or her
      with unpleasant noise. When narcissists displayed greater dACC activation during
      rejection, they behaved aggressively. But there was only a weak or nonsignificant
      relation between narcissism and aggression among participants with a blunted dACC
      response. Narcissism's role in aggressive retaliation to interpersonal threats is
      likely determined by the extent to which the brain's discrepancy detector
      registers the newly created gap between the grandiose and threatened selves.

PMID- 25564938
TI  - Committed to Life: Adolescents' and Young Adults' Experiences of Living with
      Fontan Circulation.
AB  - BACKGROUND: Single ventricle defects are among the most complex congenital heart
      defects and the development of advanced surgical procedures in recent decades has
      created the first generation of adolescents and young adults living with this
      condition. Yet little is known about how these individuals experience life and
      what impact the heart defect has on their life in general. OBJECTIVE: The aim was
      to illuminate and gain a deeper understanding of adolescents' and young adults'
      experiences of living with a surgically palliated univentricular heart. DESIGN:
      Seven open-ended in-depth interviews were conducted, transcribed, and analyzed
      according to the henomenological hermeneutical method. All adolescents and young
      adults operated before 1995 according to the Fontan procedure or the total cavo
      pulmonary connection procedure at one pediatric cardiology unit were included in
      the study. They were 17-32 years of age (median age 22 years). RESULTS: The
      interpretation of the interview transcripts showed that the participants
      experienced living with a surgically palliated univentricular heart in terms of
      feeling exceptional, strong, and healthy. This was supported by two structural
      analyses, where three themes emerged: happiness over being me, focusing on
      possibilities, and being committed to life. CONCLUSION: Living with a Fontan
      circulation included negative experiences but the analyses clearly demonstrated a
      feeling of being strong and healthy. An appreciation of having survived and being
      committed to life was found to be an integral part of the development of the
      interviewees' existential growth. This probably strengthens them further in their
      ability to balance expectations and hurdles in life. This study provides valuable
      insights into the experience of patients after the Fontan procedure and the
      importance of a positive health care environment throughout their lives.

PMID- 25564939
TI  - A case of idiopathic pterygiuminversum unguis: response to electrodissection.

PMID- 25564940
TI  - The Eastern Quebec Telepathology Network: a three-year experience of clinical
      diagnostic services.
AB  - BACKGROUND: The Eastern Quebec Telepathology Network (called Reseau de
      Telepathologie de l'Est du Quebec in French) was created to provide uniform
      diagnostic telepathology services in a huge territory with low population
      density. We report our first 3-year experience. METHODS: The network was funded
      equally by the Quebec ministry of Health and Canada Health Infoway, a federal
      telehealth funding agency. The coverage includes intraoperative consultations
      (IOC), expert opinions, urgent analyses and supervision of macroscopic
      description. The deployment of the equipment and software started in 2010 and
      clinical activities began in January 2011. This network comprises 24 hospitals
      providing oncologic surgery, of which 7 have no pathology laboratory and 4 have a
      pathology laboratory but no pathologist. The real-time gross evaluation during
      IOC was performed using a macroscopy station and the sample selection was
      performed distantly by a technician, a pathology assistant or the surgeon under
      on-site pathologist supervision. Slides were scanned into whole-slide images
      (WSI). RESULTS: As per March 2014, 7,440 slides had been scanned for
      primary/urgent diagnosis; 1,329 for IOC cases and 2,308 for expert opinions. A
      98% concordance rate was found for IOC compared to paraffin material and the
      average turnaround time was 20 minutes. Expert opinion reports were signed out
      within 24 hours in 68% of cases and within 72 hours in 85%. A recent multi-method
      evaluation study of the Network demonstrated that, thanks to telepathology: 1.
      interruption of IOC service was prevented in hospitals with no pathologist on
      site; 2. two-stage surgeries and patients transfers were prevented according to
      surgeons and pathologists; 3. retention and recruitment of surgeons in remote
      hospitals were facilitated; and 4. professional isolation among pathologists
      working alone was reduced. This study also demonstrated that wider adoption of
      telepathology would require technological improvement and that the sustainability
      of the network requires better coordination and the development of a supra
      regional pathology organisation. CONCLUSION: The Eastern Quebec Telepathology
      Network allowed the maintenance of rapid and high quality pathology services in
      more than 20 sites disseminated on a huge territory. A second phase is underway
      to expand telepathology to other regions across the province.

PMID- 25564937
TI  - Immunomodulatory role of microRNAs transferred by extracellular vesicles.
AB  - The immune system is composed of different cell types localised throughout the
      organism to sense and respond to pathological situations while maintaining
      homeostasis under physiological conditions. Intercellular communication between
      immune cells is essential to coordinate an effective immune response and involves
      both cell contact dependent and independent processes that ensure the transfer of
      information between bystander and distant cells. There is a rapidly growing body
      of evidence on the pivotal role of extracellular vesicles (EVs) in cell
      communication and these structures are emerging as important mediators for immune
      modulation upon delivery of their molecular cargo. In the last decade, EVs have
      been shown to be efficient carriers of genetic information, including microRNAs
      (miRNAs), that can be transferred between cells and regulate gene expression and
      function on the recipient cell. Here, we review the current knowledge of
      intercellular functional transfer of EV-delivered miRNAs and their putative role
      in immune regulation. 

PMID- 25564941
TI  - Association between genetic polymorphisms in interferon regulatory factor 5
      (IRF5) gene and Malaysian patients with Crohn's disease.
AB  - OBJECTIVE: The study aimed to investigate the association between the interferon
      regulatory factor 5 (IRF5) gene polymorphisms and the onset of Crohn's disease
      (CD) in a Malaysian cohort. METHODS: Genomic DNA was extracted from blood samples
      collected from 91 CD patients and 100 healthy individuals via a conventional
      phenol-chloroform extraction method. Screening of the four target single
      nucleotide polymorphisms (SNPs), including rs3807306, rs4728142, rs10954213 and
      rs11770589 was carried out in a real-time polymerase chain reaction (PCR) thermal
      cycler using TaqMan genotyping assay. The genetic data obtained was subsequently
      subjected to statistical analysis to relate the SNPs to the onset of CD in the
      Malaysian population. The genotyping assay and data were further validated
      selectively by conventional PCR amplification of the SNP sites and DNA
      sequencing. RESULTS: The rs3807306 G allele was a risk factor for CD (OR 2.3630,
      P = 0.00004), whereas the homozygous T genotype was protective against the
      disease (OR 0.2038, P = 0.00004). The heterozygous A/G genotype of rs10954213 was
      significantly associated with CD (OR 4.319, P = 0.0377). On the other hand, the
      homozygous A and heterozygous A/G genotypes of the rs11770589 were significant in
      the controls (OR 0.4242, P = 0.0166) and patients (OR 2.000, P = 0.0179),
      respectively. In the ethnic-stratification analysis, the rs11770589 homozygous A
      genotype was protective in Indians (OR 0.1551, P = 0.0112). CONCLUSION: IRF5 gene
      polymorphisms may play a role in the development of CD in the Malaysian
      population.

PMID- 25564943
TI  - Multiple phase transition and scaling law for poly(ethylene oxide)-poly(propylene
      oxide)-poly(ethylene oxide) triblock copolymer in aqueous solution.
AB  - The multiple phase transition and the scaling behavior of a poly(ethylene oxide)
      poly(propylene oxide)-poly(ethylene oxide) triblock copolymer (Pluronic F127,
      PEO100-PPO65-PEO100) have been studied by micro-differential scanning calorimetry
      and rheology. The scaling behavior of the triblock copolymer was examined using
      the Winter-Chambon criterion to obtain the critical gel temperature Tgel and the
      scaling exponent n. n was found to decrease linearly with increasing copolymer
      concentration. A stable hard gel was formed, but the hard gel was transformed
      into a soft gel upon further heating. Increasing copolymer concentration led to
      the increase in the temperature of hard-soft gel transition, while the sol-gel
      transition temperature decreased with increasing copolymer concentration. A phase
      diagram has been determined, which is able to classify unimers, micelles, hard
      gel, and soft gel regions upon heating. In addition, the scaling relation of the
      plateau modulus Ge with copolymer concentration was also obtained as Ge ~ c(3.0)
      for both soft gel and hard gel. 

PMID- 25564942
TI  - Reversal of aging-related emotional memory deficits by norepinephrine via
      regulating the stability of surface AMPA receptors.
AB  - Aging-related emotional memory deficit is a well-known complication in
      Alzheimer's disease and normal aging. However, little is known about its
      molecular mechanism. To address this issue, we examined the role of
      norepinephrine (NE) and its relevant drug desipramine in the regulation of
      hippocampal long-term potentiation (LTP), surface expression of AMPA receptor,
      and associative fear memory in rats. We found that there was a defective
      regulation of NE content and AMPA receptor trafficking during fear conditioning,
      which were accompanied by impaired emotional memory and LTP in aged rats.
      Furthermore, we also found that the exogenous upregulation of NE ameliorated the
      impairment of LTP and emotional memory via enhancing AMPA receptor trafficking in
      aged rats, and the downregulation of NE impaired LTP in adult rats. Finally,
      acute treatment with NE or desipramine rescued the impaired emotional memory in
      aged rats. These results imply a pivotal role for NE in synaptic plasticity and
      associative fear memory in aging rats and suggest that desipramine is a potential
      candidate for treating aging-related emotional memory deficit. 

PMID- 25564944
TI  - Lung-derived SSEA-1(+) stem/progenitor cells inhibit allergic airway inflammation
      in mice.
AB  - BACKGROUND: Asthma is characterized by chronic airway inflammation and airway
      hyperresponsiveness (AHR). Little is known about the role of pulmonary
      stem/progenitor cells (PSCs) in allergic airway inflammation. METHODS: To
      identify and investigate the role of PSCs in the bronchial epithelium of neonatal
      mice, we developed an enzyme-based digestion method to obtain single-cell
      suspension from lung tissues. Characterization of PSCs was performed using flow
      cytometry, real-time PCR, immunofluorescence staining, confocal microscopy, and
      scanning electron microscopy. The effects of SSEA-1(+) (stage-specific embryonic
      antigen-1) PSCs was studied in an in vivo model of ovalbumin-induced allergic
      inflammation and an in vitro model of cell-based regulation using flow cytometry,
      real-time PCR, and immune-blotting. RESULTS: Single-cell suspensions derived from
      neonatal lung tissue included populations that expressed either SSEA-1(+) or Sca
      1(+) (stem cell antigen-1). The SSEA-1(+) PSCs were highly prevalent in neonatal
      mice, and they were rare in adult mice. Enriched neonatal SSEA-1(+) PSCs had the
      ability of self-renewal and differentiated into pneumocytes and tracheal
      epithelial cells. SSEA-1(+) PSCs reduced AHR and airway damage in asthmatic mice
      by decreasing eosinophil infiltration, inhibiting chemokines/cytokines
      production, and preserving the level of CCSP. CONCLUSIONS: Here, we demonstrated
      that neonatal SSEA-1(+) PSCs play an immunomodulatory role in the progression of
      asthma by reducing lung damage and inhibiting inflammatory responses. Further
      understanding the molecular mechanisms of neonatal SSEA-1(+) PSCs might shed
      light on exploring the novel therapeutic approaches for allergic airway
      inflammation.

PMID- 25564945
TI  - Mechanism of catalytic ozonation in Fe 2O3/Al 2O3@SBA-15 aqueous suspension for
      destruction of ibuprofen.
AB  - Fe2O3 and/or Al2O3 were supported on mesoporous SBA-15 by wet impregnation and
      calcinations with AlCl3 and FeCl3 as the metal precursor and were characterized
      by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Fourier
      transform infrared spectra (FTIR) of adsorbed pyridine. Fe2O3/Al2O3@SBA-15 was
      found to be highly effective for the mineralization of ibuprofen aqueous solution
      with ozone. The characterization studies showed that Al-O-Si was formed by the
      substitution of Al(3+) for the hydrogen of surface Si-OH groups, not only
      resulting in high dispersion of Al2O3 and Fe2O3 on SBA-15, but also inducing the
      greatest amount of surface Lewis acid sites. By studies of in situ attenuated
      total reflection FTIR (ATR-FTIR), in situ Raman, and electron spin resonance
      (ESR) spectra, the chemisorbed ozone was decomposed into surface atomic oxygen
      species at the Lewis acid sites of Al(3+) while it was converted into surface
      adsorbed (*)OHads and O2(*-) radicals at the Lewis acid sites of Fe(3+). The
      combination of both Lewis acid sites of iron and aluminum onto Fe2O3/Al2O3@SBA-15
      enhanced the formation of (*)OHads and O2(*-) radicals, leading to highest
      reactivity. Mechanisms of catalytic ozonation were proposed for the tested
      catalysts on the basis of all the experimental information. 

PMID- 25564947
TI  - [Retrospect of conjoined German and Austrian Societies of Plastic Surgery Annual
      Meeting 2014 in Munich].

PMID- 25564946
TI  - Trends in emergent hernia repair in the United States.
AB  - IMPORTANCE: Abdominal wall hernia is one of the most common conditions
      encountered by general surgeons. Rising rates of abdominal wall hernia repair
      have been described; however, population-based evidence concerning incidence
      rates of emergent hernia repair and changes with time are unknown. OBJECTIVE: To
      examine trends in rates of emergent abdominal hernia repair within the United
      States for inguinal, femoral, ventral, and umbilical hernias from January 1,
      2001, to December 31, 2010. DESIGN, SETTING, AND PARTICIPANTS: A retrospective
      analysis of adults with emergent hernia repair using National Center for Health
      Statistics data, a nationally representative sample of inpatient hospitalizations
      in the United States that occurred from January 1, 2001, to December 31, 2010.
      All emergent hernia repairs were identified during the study period. MAIN
      OUTCOMES AND MEASURES: Incidence rates per 100,000 person-years, age, and sex
      adjusted to the 2010 US census population estimates were calculated for selected
      subcategories of emergent hernia repairs and time trends were evaluated. RESULTS:
      An estimated 2.3 million inpatient abdominal hernia repairs were performed from
      2001 to 2010; of which an estimated 567,000 were performed emergently. A general
      increase in the rate of total emergent hernias was observed from 16.0 to 19.2
      emergent hernia repairs per 100,000 person-years in 2001 and 2010, respectively.
      In 2010, emergent hernia rates were highest among adults 65 years and older, with
      71.3 and 42.0 emergent hernia repairs per 100,000 person-years for men and women,
      respectively. As expected, femoral hernia rates were higher among women while
      emergent inguinal hernia rates were higher among men. Rates of emergent
      incisional hernia repair were high but relatively stable among older women, with
      24.9 and 23.5 per 100,000 person-years in 2001 and 2010, respectively. However,
      rates of emergent incisional hernia repair among older men rose significantly,
      with 7.8 to 32.0 per 100,000 person-years from 2001 to 2010, respectively.
      CONCLUSIONS AND RELEVANCE: These increasing rates of emergent incisional hernia
      repair are troublesome owing to the significantly increased risk morbidity and
      mortality associated with emergent hernia repair. While this increased mortality
      risk is multifactorial, it is likely associated with older age and the
      accompanying serious comorbidities.

PMID- 25564948
TI  - [Landmark-based statistical procrustes analysis in the examination of breast
      shape and symmetry].
AB  - AIM: The aim of this presentation is the explanation of a mathematical analysis
      of a landmark-based procrustes calculation. The various components of breast
      symmetry and their impact on breast reconstruction have been examined. METHOD: In
      an objective breast shape analysis asymmetries are quantified as a measure of the
      difference between a 3D landmark configuration of a breast and its mirror image.
      10 landmarks, 4 on each side and 2 for a definition of the midline were defined.
      For each landmark the 3D coordinates were calculated statistically with the help
      of the software Programme R. Over a midline from the jugulum to the manubrium
      sterni, a mirror image of the breast was constructed. The data for the breast to
      be reconstructed and the non-operated breast from 44 patients were investigated.
      The statistical differences of the Procrustes analysis were used for an asymmetry
      score and the proportions of the individual components were calculated. These
      included size, location and orientation of the breast as well as the individual
      inherent morphological surface form data of the breast. RESULTS: All 44 patients
      exhibited breast asymmetries and the mean asymmetry score amounted to 0.52. A
      calculation of the proportions of the individual components making up the
      asymmetry score revealed that morphological surface data made the largest
      contribution to the asymmetry score, closely followed by location, i. e.,
      positioning of the breast on the thoracic wall. In contrast, the size of the
      breast and its orientation were of lesser relevance. CONCLUSION: When considering
      breast symmetry in plastic surgery, the form plays a more important role than the
      size as objectively calculated by the statistical procrustes analysis. Almost
      equally important as the form is the positioning of the breast on the thoracic
      wall which contributes significantly more to total breast symmetry than axial
      displacements.

PMID- 25564949
TI  - [Treatment of Dupuytren's disease with collagenase - a 1-year follow-up of 37
      patients].
AB  - INTRODUCTION: The efficiency of collagenase of Clostridium histolyticum (CCH;
      Xiapex) in the treatment of Dupuytren's contracture has been proved in phase III
      studies. This retrospective study aims to evaluate our clinical results after the
      use of CCH. PATIENTS AND METHODS: The study included 40 Dupuytren's contractures
      in 37 patients. There were 32 male and 5 female patients; their average age was
      66 years. The most affected finger was the ring finger (55%; 22/40), followed by
      the little finger (30%; 12/40) and the middle finger (15; 6/40). 14 fingers (35%)
      presented isolated contractures of the metacarpophalangeal joint whereas an
      isolated contracture of the proximal interphalangeal joint was evident in 8 (20%)
      fingers. 18 (45%) fingers presented combined MCP and PIP flexion contractures.
      None of the patients underwent any treatment prior to this study. A retrospective
      chart review was performed of all patients. Follow-up examinations were performed
      seven days, fourteen days, three months, six months and one year after the
      intervention. The follow-up examination included goniometry of each affected
      finger to assess the range of motion (ROM) before and after cord breaking.
      Further patient-reported outcome was accessed concerning postinterventional
      complaints, impairment of sensibility and satisfaction with the treatment.
      RESULTS: The range of motion improved in all fingers. Full extension of the
      affected finger without any contracture could be observed in 93% of the MCP
      contractures, 38% of the PIP contractures and in 28% of the combined MCP and PIP
      contractures. Incomplete cord breaking could be observed in 9 (22.5%) fingers. In
      8 fingers (20%) skin tears occurred after joint manipulation but healed up
      without any further surgical intervention. The recurrence rate at the latest
      follow-up was 2.5% (1/40). Patient satisfaction was high and none of the patients
      reported any complaints at the latest follow-up. CONCLUSION: The best results
      could be achieved in patients with isolated contractures of the MCP joint.
      Regarding the good functional results, the low complication rates and the high
      patient satisfaction, CCH represents a simple and effective treatment for
      Dupuytren's contracture in selected cases.

PMID- 25564951
TI  - [Pseudolymphatic allergic immune reaction after tattooing].
AB  - Allergic reactions occurring after tattooing, especially after the use of red
      tattoo ink ingredients are relatively rare. We report a painful skin reaction
      occurring 6 months after the tattoing of the right lower extremity in a 30-year
      old female patient. Pathohistological and immunchemical results confirmed a
      pseudolymphoma. Only the tangential excision of the affected areas led to a
      sufficient healing process. Split thickness skin grafts were used for defect
      coverage. 2 years later, the patient was still pain free and the wounds had
      healed completely without any irritation. 

PMID- 25564950
TI  - [Acute upper limb embolism in a severely burned patient].
AB  - Thrombosis and pulmonary embolisms are the most common complications in the
      hospital. The need for anticoagulation during hospital stay is obligatory.
      Arterial embolisms are rare. They often take place in patients with a pre
      existing peripheral artery occlusive disease or in patients with atrial
      fibrillation. The most common complications in burn patients are wound infection,
      pneumonia, catheter-associated infections and paralytic ileus. There are almost
      no data available regarding arterial embolism in burn patients. Therefore we
      would like to present the case of a 60-year-old woman who was injured by a fire
      at home and was transported to our special burn unit. She sustained partial
      thickness burns of both legs and buttocks. The TBSA was 15%. During the first
      days of clinical stay the patient suffered from a pain induced movement reduction
      of the left hand. There were no peripheral pulses palpable or by pulsed-wave
      Doppler detectable. An urgent selected angiography of the left arm was performed
      and a arterial embolism of the proximal part of the a. brachialis was detected.
      The patient was operated immediately. After debridement and split-skin graft of
      the burn wounds the patient was taken to rehabiliation after 35 days. 

PMID- 25564952
TI  - [HaMiPla Best Paper Meeting of the DGPRAC Annual Conference in Munich - your
      favorites 2013].

PMID- 25564953
TI  - [Annual meeting of the German Society for Surgery of the Hand (DGH) in Baden
      Baden].

PMID- 25564955
TI  - Identical Hg isotope mass dependent fractionation signature during methylation by
      sulfate-reducing bacteria in sulfate and sulfate-free environment.
AB  - Inorganic mercury (iHg) methylation in aquatic environments is the first step
      leading to monomethylmercury (MMHg) bioaccumulation in food webs and might play a
      role in the Hg isotopic composition measured in sediments and organisms.
      Methylation by sulfate reducing bacteria (SRB) under sulfate-reducing conditions
      is probably one of the most important sources of MMHg in natural aquatic
      environments, but its influence on natural Hg isotopic composition remains to be
      ascertained. In this context, the methylating SRB Desulfovibrio
      dechloracetivorans (strain BerOc1) was incubated under sulfate reducing and
      fumarate respiration conditions (SR and FR, respectively) to determine Hg species
      specific (MMHg and IHg) isotopic composition associated with methylation and
      demethylation kinetics. Our results clearly establish Hg isotope mass-dependent
      fractionation (MDF) during biotic methylation (-1.20 to +0.580/00 for
      delta(202)Hg), but insignificant mass-independent fractionation (MIF) (-0.12 to
      +0.150/00 for Delta(201)Hg). During the 24h of the time-course experiments Hg
      isotopic composition in the produced MMHg becomes significantly lighter than the
      residual IHg after 1.5h and shows similar delta(202)Hg values under both FR and
      SR conditions at the end of the experiments. This suggests a unique pathway
      responsible for the MDF of Hg isotopes during methylation by this strain
      regardless the metabolism of the cells. After 9 h of experiment, significant
      simultaneous demethylation is occurring in the culture and demethylates
      preferentially the lighter Hg isotopes of MMHg. Therefore, depending on their
      methylation/demethylation capacities, SRB communities in natural sulfate reducing
      conditions likely have a significant and specific influence on the Hg isotope
      composition of MMHg (MDF) in sediments and aquatic organisms.

PMID- 25564956
TI  - Notepad-like triboelectric generator for efficiently harvesting low-velocity
      motion energy by interconversion between kinetic energy and elastic potential
      energy.
AB  - Great attention has been paid to nanogenerators that harvest energy from ambient
      environments lately. In order to give considerable output current, most
      nanogenerators require high-velocity motion that in most cases can hardly be
      provided in our daily life. Here we report a notepad-like triboelectric generator
      (NTEG), which uses simple notepad-like structure to generate elastic deformation
      so as to turn a low-velocity kinetic energy into high-velocity kinetic energy
      through the conversion of elastic potential energy. Therefore, the NTEG can
      achieve high current output under low-velocity motion, which completely
      distinguishes it from tribogenerators previously reported. The factors that may
      affect the output performance are explored, including the number of slices,
      active length of slice, press speed, and vertical displacement. In addition, the
      working mechanism is systematically studied, indicating that the efficiency of
      the generator can be greatly enhanced by interconversion between kinetic energy
      and elastic potential energy. The short-circuit current, the open-circuit
      voltage, and power density are 205 MUA and 470 V and 9.86 W/m(2), respectively,
      which is powerful enough to light up hundreds of light-emitting diodes (LEDs) and
      charge a commercial capacitor. Besides, NTEGs have been successfully applied to a
      self-powered door monitor. 

PMID- 25564957
TI  - Atrophoderma Vermiculatum: A Cutaneous Feature of Loeys-Dietz Syndrome.

PMID- 25564958
TI  - Morin hydrate attenuates Staphylococcus aureus virulence by inhibiting the self
      assembly of alpha-hemolysin.
AB  - AIMS: To investigate the mechanism by which morin hydrate inhibits the haemolytic
      activity of alpha-hemolysin (Hla), a channel-forming toxin that is important for
      the pathogenesis of disease in experimental animals, and its therapeutic effect
      against Staphylococcus aureus pneumonia in a mouse model. METHODS AND RESULTS:
      The results from the in vitro (haemolysis, western blot and cytotoxicity assays)
      and in vivo (mouse model of intranasal lung infection) experiments indicated that
      morin hydrate, a natural compound with little anti-Staph. aureus activity, could
      effectively antagonize the cytolytic activity of Hla, alleviate human lung cell
      injury, and protect against mortality of Staph. aureus pneumonia in a mouse model
      of infection. Molecular dynamics simulations, free energy calculations and
      mutagenesis assays were further employed to determine the catalytic mechanism of
      inhibition, which indicated that a direct binding of morin to the 'Stem' domain
      of Hla (residues I107 and T109) and the concomitant change in conformation led to
      the inhibition of the self-assembly of the heptameric transmembrane pore, thus
      inhibiting the biological activity of Hla for cell lysis. CONCLUSIONS: Morin
      inhibited Staph. aureus virulence via inhibiting the haemolytic activity of alpha
      hemolysin. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggested that
      morin is a promising candidate for the development of anti-virulence therapeutic
      agents for the treatment of Staph. aureus infections.

PMID- 25564959
TI  - CD38 and interleukin 6 gene polymorphism in egyptians with diffuse large B-cell
      lymphoma (DLBCL).
AB  - Given the importance of understanding the genetic variations involved in the
      pathogenesis of non-Hodgkin's lymphoma (NHL), this pilot study was designed to
      investigate the impact of CD38 (184C/G; rs6449182) and IL-6 (-174 G/C; rs1800795)
      gene polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma
      (DLBCL); major types of NHL. To the best of our knowledge, this study is the
      first one that examines CD38 polymorphism in the NHL. Genotyping polymorphism is
      performed using restriction fragment length polymorphism-polymerase chain
      reaction (RFLP-PCR) for CD38 and Mutagenically separated PCR (MS-PCR) for IL-6 in
      100 Egyptian NHL patients with DLBCL subtype and 119 normal controls. The serum
      level of IL-6 was measured using Enzyme-linked immunosorbent assay (ELISA). CD38
      (184C/G) genotype is significantly increased in NHL patients (p < 0.01), while
      the GG genotype is significantly increased in controls (p < 0.05). Only two
      genotypes were found (GG and GC) in IL-6 (-174), no CC in our NHL patients and
      only one case in the controls. Insignificant change in IL-6 (-174 G/C) genotypes
      was recorded. Significantly increased serum IL-6 (p < 0.05) was positively
      correlated (r = 0.17; p < 0.05) with the disease. Taken together, our data
      stressed the importance of CD38 gene polymorphism in developing DLBCL. Our pilot
      study indicates that CD38 (184) CG genotype might play a role in DLBCL
      susceptibility in Egyptians. Additional prospective studies on larger population
      are needed to confirm our findings. 

PMID- 25564961
TI  - Passive acoustic mapping of magnetic microbubbles for cavitation enhancement and
      localization.
AB  - Magnetic targeting of microbubbles functionalized with superparamagnetic
      nanoparticles has been demonstrated previously for diagnostic (B-mode) ultrasound
      imaging and shown to enhance gene delivery in vitro and in vivo. In the present
      work, passive acoustic mapping (PAM) was used to investigate the potential of
      magnetic microbubbles for localizing and enhancing cavitation activity under
      focused ultrasound. Suspensions of magnetic microbubbles consisting of 1,2
      distearoyl-sn-glycero-3-phosphocholine (DSPC), air and 10 nm diameter iron oxide
      nanoparticles were injected into a tissue mimicking phantom at different flow
      velocities (from 0 to 50 mm s(-1)) with or without an applied magnetic field.
      Microbubbles were excited using a 500 kHz single element focused transducer at
      peak negative focal pressures of 0.1-1.0 MPa, while a 64 channel imaging array
      passively recorded their acoustic emissions. Magnetic localization of microbubble
      induced cavitation activity was successfully achieved and could be resolved using
      PAM as a shift in the spatial distribution and increases in the intensity and
      sustainability of cavitation activity under the influence of a magnetic field.
      Under flow conditions at shear rates of up to 100 s(-1) targeting efficacy was
      maintained. Application of a magnetic field was shown to consistently increase
      the energy of cavitation emissions by a factor of 2-5 times over the duration of
      exposures compared to the case without targeting, which was approximately
      equivalent to doubling the injected microbubble dose. These results suggest that
      magnetic targeting could be used to localize and increase the concentration of
      microbubbles and hence cavitation activity for a given systemic dose of
      microbubbles or ultrasound intensity. 

PMID- 25564962
TI  - Inducible and endothelial nitric synthetase expression and nitrotyrosine
      accumulation in iris vasculature of patients with primary open-angle glaucoma: a
      pilot study.
AB  - BACKGROUND: The "double-faced" effect of nitric oxide (NO) is thought to play an
      important role in triggering and progression of glaucoma. MATERIAL/METHODS: Iris
      samples were obtained during iridectomy in 35 patients (mean age of 65.4+/-5.3
      years) with diagnosed primary open-angle glaucoma (POAG). The controls were
      collected postmortem from 10 donors with a mean age of 62.2+/-1.9 years. Visual
      field defects were evaluated by perimetry. The Hodapp-Parrish-Anderson
      classification was used to divide patients into 3 visual field defect groups. The
      intraocular pressure was measured 3 times before surgery using applanation
      tonometry. The phenotype activity of nitric oxide synthase (NOS) isoenzymes
      (endothelial--eNOS and inducible--iNOS) and expression of nitrotyrosine in iris
      vasculature was assessed. RESULTS: Significant differences were found between
      glaucoma patients and the controls in eNOS and iNOS activity (Mann-Whitney test,
      U=35.5, Z=-2.037, p=0.04 and U=21, Z=2.69, p=0.007, respectively). In addition,
      the results showed an upregulation of nitrotyrosine in the capillary endothelial
      cells in the study group, which was associated with the duration of diagnosed
      glaucoma (R-Spearman of 0.33, p=0.0047) and visual field mean defect MD (R
      Spearman of 0.29, p=0.019). Moreover, the activity of nitrotyrosine was
      significantly correlated with iNOS immunoreactivity (R-Spearman of 0.5,
      p=0.0001). However, the iNOS activity significantly varied among Hodapp-Parrish
      Anderson groups (p=0.03). CONCLUSIONS: Our observations confirmed the association
      between glaucomatous disturbances and upregulation of iNOS, together with
      increased nitrotyrosine storage.

PMID- 25564960
TI  - Task-based measures of image quality and their relation to radiation dose and
      patient risk.
AB  - The theory of task-based assessment of image quality is reviewed in the context
      of imaging with ionizing radiation, and objective figures of merit (FOMs) for
      image quality are summarized. The variation of the FOMs with the task, the
      observer and especially with the mean number of photons recorded in the image is
      discussed. Then various standard methods for specifying radiation dose are
      reviewed and related to the mean number of photons in the image and hence to
      image quality. Current knowledge of the relation between local radiation dose and
      the risk of various adverse effects is summarized, and some graphical depictions
      of the tradeoffs between image quality and risk are introduced. Then various dose
      reduction strategies are discussed in terms of their effect on task-based
      measures of image quality. 

PMID- 25564963
TI  - Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and
      chemosensitivity in 3-dimensional Gelfoam(r) histoculture but not 2-dimensional
      culture as visualized with real-time FUCCI imaging.
AB  - The phase of the cell cycle can determine whether a cancer cell can respond to a
      given drug. We previously reported monitoring of real-time cell cycle dynamics of
      cancer cells throughout a live tumor, intravitally in live mice, using a
      fluorescence ubiquitination-based cell-cycle indicator (FUCCI). Approximately 90%
      of cancer cells in the center and 80% of total cells of an established tumor are
      in G0/G1 phase. Longitudinal real-time imaging demonstrated that cytotoxic agents
      killed only proliferating cancer cells at the surface and, in contrast, had
      little effect on quiescent cancer cells, which are the vast majority of an
      established tumor. Moreover, resistant quiescent cancer cells restarted cycling
      after cessation of chemotherapy. These results suggested why most drugs currently
      in clinical use, which target cancer cells in S/G2/M, are mostly ineffective on
      solid tumors. In the present report, we used FUCCI imaging and Gelfoam(r)
      collagen-sponge-gel histoculture, to demonstrate in real time, that the cell
      cycle phase distribution of cancer cells in Gelfoam(r) and in vivo tumors is
      highly similar, whereby only the surface cells proliferate and interior cells are
      quiescent in G0/G1. This is in contrast to 2D culture where most cancer cells
      cycle. Similarly, the cancer cells responded similarly to toxic chemotherapy in
      Gelfoam(r) culture as in vivo, and very differently than cancer cells in 2D
      culture which were much more chemosensitive. Gelfoam(r) culture of FUCCI
      expressing cancer cells offers the opportunity to image the cell cycle of cancer
      cells continuously and to screen for novel effective therapies to target
      quiescent cells, which are the majority in a tumor and which would have a strong
      probability to be effective in vivo.

PMID- 25564965
TI  - A nanoparticulate drug-delivery system for 20(S)-protopanaxadiol: formulation,
      characterization, increased oral bioavailability and anti-tumor efficacy.
AB  - As with many other hydrophobic anticancer agents, 20(S)-protopanaxadiol (PPD) has
      a very low oral bioavailability. In this study, a precipitation-combined
      ultrasonication technique was used to prepare PPD nanosuspensions. The mean
      particle size of the nanosuspensions was approximately 222 +/- 12 nm, the drug
      payload achieved 50% after lyophilization and the maximum PPD concentration can
      reach 100 mg/ml, which is over 30 000 times the solubility of PPD in aqueous
      solution (3 MUg/ml). After oral administration, the Cmax and AUClast values of
      PPD nanosuspensions were approximately 3.66-fold and 3.48-fold as those of PPD
      coarse suspensions, respectively. In contrast to the free drug solution, PPD
      nanosuspensions showed higher in vitro anti-tumor activity against HepG-2 cells
      (an IC50 value of 1.40 versus 5.83 MUg/ml at 24 h, p < 0.01). The in vivo study
      in H22-tumor-bearing mice demonstrated that PPD nanosuspensions showed good anti
      tumor efficacy with an inhibition rate of 79.47% at 100 mg/kg, while 50 mg/kg of
      cyclophosphamide was displayed as positive control, and the inhibition rate was
      87.81%. Considering the highest drug payload, oral bioavailability reported so
      far, significant anti-tumor efficacy and excellent safety of encapsulated drugs,
      PPD nanosuspensions could be used in potential effective strategies for
      anticancer therapy; further investigation is ongoing.

PMID- 25564964
TI  - Nanoparticle-based topical ophthalmic formulation for sustained release of
      stereoisomeric dipeptide prodrugs of ganciclovir.
AB  - Poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of Val-Val dipeptide
      monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val
      D-Val-GCV (LDGCV) and D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in
      thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex
      virus type 1 (HSV-1)-induced viral corneal keratitis. Nanoparticles containing
      prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique
      using various PLGA polymers with different drug/polymer ratios. Nanoparticles
      were characterized with respect to particle size, entrapment efficiency,
      polydispersity, drug loading, surface morphology, zeta potential and
      crystallinity. Prodrugs-loaded NP were incorporated into in situ gelling system.
      These formulations were examined for in vitro release and cytotoxicity. The
      results of optimized entrapment efficiencies of LLGCV-, LDGCV- and DLGCV-loaded
      NP are of 38.7 +/- 2.0%, 41.8 +/- 1.9%, and 45.3 +/- 2.2%; drug loadings 3.87 +/-
      0.20%, 2.79 +/- 0.13% and 3.02 +/- 0.15%; yield 85.2 +/- 3.0%, 86.9 +/- 4.6% and
      76.9 +/- 2.1%; particle sizes 116.6 +/- 4.5, 143.0 +/- 3.8 and 134.1 +/- 5.2 nm;
      and zeta potential -15.0 +/- 4.96, -13.8 +/- 5.26 and -13.9 +/- 5.14 mV,
      respectively. Cytotoxicity studies suggested that all the formulations are non
      toxic. In vitro release of prodrugs from NP showed a biphasic release pattern
      with an initial burst phase followed by a sustained phase. Such burst effect was
      completely eliminated when NP were suspended in thermosensitive gels with near
      zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive
      gels can thus serve as a promising drug delivery system for the treatment of
      anterior eye diseases.

PMID- 25564966
TI  - Toward a benchmarking data set able to evaluate ligand- and structure-based
      virtual screening using public HTS data.
AB  - Virtual screening has the potential to accelerate and reduce costs of probe
      development and drug discovery. To develop and benchmark virtual screening
      methods, validation data sets are commonly used. Over the years, such data sets
      have been constructed to overcome the problems of analogue bias and artificial
      enrichment. With the rapid growth of public domain databases containing high
      throughput screening data, such as the PubChem BioAssay database, there is an
      increased possibility to use such data for validation. In this study, we identify
      PubChem data sets suitable for validation of both structure- and ligand-based
      virtual screening methods. To achieve this, high-throughput screening data for
      which a crystal structure of the bioassay target was available in the PDB were
      identified. Thereafter, the data sets were inspected to identify structures and
      data suitable for use in validation studies. In this work, we present seven data
      sets (MMP13, DUSP3, PTPN22, EPHX2, CTDSP1, MAPK10, and CDK5) compiled using this
      method. In the seven data sets, the number of active compounds varies between 19
      and 369 and the number of inactive compounds between 59 405 and 337 634. This
      gives a higher ratio of the number of inactive to active compounds than what is
      found in most benchmark data sets. We have also evaluated the screening
      performance using docking and 3D shape similarity with default settings. To
      characterize the data sets, we used physicochemical similarity and 2D fingerprint
      searches. We envision that these data sets can be a useful complement to current
      data sets used for method evaluation. 

PMID- 25564967
TI  - Oxygenic photosynthesis-specific subunits of cyanobacterial NADPH dehydrogenases.
AB  - Cyanobacterial NADPH dehydrogenase (NDH-1) or NDH-1-like complex is localized in
      the thylakoid membrane and participates in a variety of bioenergetic reactions,
      including respiration, cyclic electron transport around photosystem I and CO2
      uptake. Over the past decade, a significant achievement has been made in
      identifying seven oxygenic photosynthesis-specific (OPS) subunits of NDH-1
      enzyme, NdhL to NdhQ and NdhS, in several cyanobacterial strains. Six of them are
      also found in higher plants but not in nonphototrophs. This indicates an
      exclusive existence of these OPS Ndh subunits in oxygenic photosynthetic
      organisms and suggested certain role of cyanobacterial and chloroplastic NDH-1 in
      photosynthetic reactions. In this review, we describe these seven OPS subunits of
      cyanobacterial NDH-1, focusing on their identification, localization, function,
      and evolution from cyanobacteria to higher plants. A crucial role of these OPS
      subunits on the function of cyanobacterial NDH-1 is proposed.

PMID- 25564969
TI  - The development of an artificial organic networks toolkit for LabVIEW.
AB  - Two of the most challenging problems that scientists and researchers face when
      they want to experiment with new cutting-edge algorithms are the time-consuming
      for encoding and the difficulties for linking them with other technologies and
      devices. In that sense, this article introduces the artificial organic networks
      toolkit for LabVIEWTM (AON-TL) from the implementation point of view. The toolkit
      is based on the framework provided by the artificial organic networks technique,
      giving it the potential to add new algorithms in the future based on this
      technique. Moreover, the toolkit inherits both the rapid prototyping and the easy
      to-use characteristics of the LabVIEWTM software (e.g., graphical programming,
      transparent usage of other softwares and devices, built-in programming event
      driven for user interfaces), to make it simple for the end-user. In fact, the
      article describes the global architecture of the toolkit, with particular
      emphasis in the software implementation of the so-called artificial hydrocarbon
      networks algorithm. Lastly, the article includes two case studies for engineering
      purposes (i.e., sensor characterization) and chemistry applications (i.e., blood
      brain barrier partitioning data model) to show the usage of the toolkit and the
      potential scalability of the artificial organic networks technique.

PMID- 25564968
TI  - Tailored mental health care after nursing home admission: improving transfers of
      people with dementia with behavioral problems. An explorative study.
AB  - OBJECTIVES: In the Netherlands, many community-dwelling people with dementia and
      behavioral disturbances and their family caregivers receive mental health care
      from a community psychiatric nurse (CPN). To promote continuity of care for these
      persons after moving to a nursing home, a transfer intervention was developed.
      The aim of this explorative study was to evaluate this intervention and its
      implementation. METHOD: A qualitative explorative study design was used. CPNs
      visited professional nursing home carers, people with dementia and family
      caregivers six weeks after moving, advised on how to manage behavioral problems
      of their former clients and provided support to family caregivers. Twenty-two
      interviews were conducted with participants exposed to the intervention (5 CPNs,
      5 family and 12 nursing home carers) and with 11 stakeholders (i.e., nursing home
      and mental health care managers, professional caregivers) to identify
      facilitators and barriers to the implementation. Data were collected in 2012 and
      2013. RESULTS: The follow-up visit at six weeks met the need for background
      information of new admitted patients and helped family caregivers close off the
      period prior to the move. It did not meet the original purpose of providing
      nursing home staff with advice about problem behaviors on time: six weeks after
      the move was experienced as too late. CONCLUSION: The transfer intervention
      increased the awareness of nursing home staff about personal and behavioral
      characteristics of residents with dementia and supported caregivers in coping
      with the new situation. The timing of the intervention could be improved by
      scheduling it immediately after the move.

PMID- 25564970
TI  - Time and concentration dependency of P-gp, MRP1 and MRP5 induction in response to
      gemcitabine uptake in Capan-2 pancreatic cancer cells.
AB  - 1. Influx and efflux proteins play a major role in the overall uptake and
      efficacy of chemotherapeutic agents and cellular chemo-resistance. 2. The present
      study investigated the time course and dose dependency of the induction of three
      efflux proteins, P-gp, MRP1 and MRP5, in response to gemcitabine exposure in
      Capan-2 pancreatic cancer cell line at transcriptional and translational levels.
      The influence of exposure on the influx protein (ENT1), the net cellular uptake
      of the gemcitabine, the overall ATPase activity and the cell death rate were also
      measured. 3. The time course of the expression exhibited an initial rise, toward
      a plateau level. The estimated Km and Vmax confirmed that MRP5 and to a lesser
      extent MRP1 are the prominent proteins for efflux of gemcitabine. Both mRNA and
      protein expression demonstrated the time and concentration dependency of the
      induction; and the elevated ATPase activity validated that the induced efflux
      proteins are functionally active. 4. The results of the study revealed that the
      efficacy window of gemcitabine as it relates to the function of the efflux
      proteins is concentration and temporal dependent and is well correlated to the
      first 60 min of exposure.

PMID- 25564971
TI  - Control over recollection varies with context-type: ERP evidence from the
      exclusion task.
AB  - The left-parietal ERP old/new effect-an index of recollection-is often larger for
      classes of item to-be-endorsed as old (targets) than to-be-rejected items
      (nontargets), and this has been interpreted as an index of selective retrieval.
      The question of interest here was whether selective retrieval would be more
      pronounced when targets are allocated according to distinct conceptual encoding
      tasks than when designated according to spatial location. Participants saw words
      on the left/right side of fixation and made a pleasantness or function judgment
      to each. Across test-blocks, target designation varied according to the kind of
      task judgment or the study location. Robust target old/new effects were observed
      for both classes of target designation but the nontarget amplitude was smaller
      when conceptual information was targeted. The current data indicate that the
      class of to-be-retrieved information determines the extent to which recollection
      can be controlled when all other factors are held constant.

PMID- 25564972
TI  - Media coverage of smoke-free policies after their innovation.
AB  - Smoke-free policies are critical to global tobacco control, and prior research on
      media coverage of smoke-free policies primarily focused on the period when they
      were first innovated; however, the scientific basis for smoke-free policies has
      broadened, and how media coverage has changed, if at all, is unknown. The authors
      characterized the actors, arguments, and favorability of media coverage of smoke
      free policies from 2006 to 2009, by content-analyzing 452 news stories in the 4
      primary newspapers in South Carolina. Most media coverage was favorable (45%) or
      mixed (43%) toward smoke-free policies, and negative coverage decreased over time
      (B = -1.001, SE = 0.326; p = .008). The most prevalent argument concerned the
      harms of secondhand smoke (44%). A higher percentage of articles mentioned
      economic arguments against (26%) than for (17%) smoke-free policies (chi(2) =
      10.89, p < .01, for the difference between 26% and 17%), and these percentages
      did not change over time. Advocates and media should improve communications to
      more effectively represent scientific evidence regarding the null or positive
      impact of smoke-free policies on businesses.

PMID- 25564973
TI  - Journal of the Science of Food and Agriculture. Editorial.

PMID- 25564974
TI  - Three dimensional mesoscale analysis of translamellar cross-bridge morphologies
      in the annulus fibrosus using optical coherence tomography.
AB  - The defining characteristic of the annulus fibrosus (AF) of the intervertebral
      disc (IVD) has long been the lamellar structures that consist of highly ordered
      collagen fibers arranged in alternating oblique angles from one layer to the
      next. However, a series of recent histologic studies have demonstrated that AF
      lamellae contain elastin- and type VI collagen-rich secondary "cross-bridge"
      structures across lamellae. In this study, we use optical coherence tomography
      (OCT) to elucidate the three-dimensional (3-D) morphologies of these
      translamellar cross-bridges in AF tissues. Mesoscale volumetric images by OCT
      revealed a 3-D network of heterogeneously distributed cross-bridges. The results
      of this study confirm the translamellar cross-bridge is identifiable as a
      distinguishable structure, which lies in the interbundle space of adjacent
      lamellae and crisscrosses multiple lamellae in the radial direction. In contrast
      to previously proposed models extrapolated from 2-D sections, results from this
      current study show that translamellar cross-bridges exist as a complex,
      interconnected network. We also found much greater variation in lengths of cross
      bridges within the interbundle space of lamellae (0.8-1.4 mm from the current
      study versus 0.3-0.6 mm from 2-D sections). OCT-based 3-D morphology of
      translamellar cross-bridge provides novel insight into the AF structure.

PMID- 25564975
TI  - School nurses' knowledge, attitudes, perceptions of role as opinion leader, and
      professional practice regarding human papillomavirus vaccine for youth.
AB  - BACKGROUND: Because human papillomavirus (HPV) vaccine rates remain low, we
      evaluated US school nurses' knowledge, attitudes, perceptions of their role as
      opinion leaders, and professional practice regarding HPV vaccine, and assessed
      whether knowledge, attitudes, and perceptions of being an opinion leader
      influenced their professional practice regarding the HPV vaccine. METHODS: We
      used a cross-sectional design by recruiting members from the National Association
      of School Nurses. All participants (N = 505) were e-mailed a survey designed for
      this study. Structural equation modeling (SEM) tested direct and indirect
      effects. RESULTS: Overall, school nurses had knowledge about HPV and the vaccine,
      and positive attitudes toward the vaccine. They had less-than-enthusiastic
      perceptions of their role as opinion leaders regarding the vaccine and
      implemented few activities related to providing vaccine information. The model
      revealed a good fit (chi(2)=20.238 [df=8, p< .01]), with knowledge directly
      related to attitudes, attitudes directly related to perceptions and practice, and
      perceptions directly affecting practice. In our model, perceptions functioned as
      a partial mediator. CONCLUSIONS: To enhance school nurses' practice regarding the
      HPV vaccine, focus should be on increasing positive attitudes toward the vaccine
      and strengthening perceptions of their role as opinion leaders.

PMID- 25564976
TI  - The protective role of school friendship ties for substance use and aggressive
      behaviors among middle school students.
AB  - BACKGROUND: Few studies have examined the interplay among quantifiable aspects of
      peer bonds, friendship types, personal characteristics, and behavioral outcomes
      in schools in distressed neighborhoods. The aim of this study was to identify
      compensatory and protective factors that can be promoted in school-based
      prevention programs. METHODS: The sample was comprised of students in East Los
      Angeles County (N=184). We investigated the association between 3 measures of
      social influence (friends in gangs, nominations of schoolmates as friends [out
      degree], and the number of nominations received from schoolmates [in-degree]) and
      social self-control with lifetime alcohol, tobacco, inhalant, "other" drug use,
      and aggression. RESULTS: Friendships were protective for substance use and
      aggression and moderated the relationship between social self-control, substance
      use, and aggression. We found important sex differences; girls who nominated more
      friends were less likely to report alcohol use and aggression relative to boys
      but were more likely to have reported drug use as social self-control scores
      increased. CONCLUSIONS: Our results have important implications for school-based
      prevention and intervention programs. We provide preliminary evidence that school
      ties and perceptions of belongingness can mitigate the effects of several risk
      factors linked to substance use and aggression.

PMID- 25564977
TI  - The role of family and community involvement in the development and
      implementation of school nutrition and physical activity policy.
AB  - BACKGROUND: Although there are several evidence-based recommendations directed at
      improving nutrition and physical activity standards in schools, these guidelines
      have not been uniformly adopted throughout the United States. Consequently,
      research is needed to identify facilitators promoting schools to implement these
      recommendations. Therefore, this study analyzed the 2008 School Health Profiles
      Principal Survey (Profiles) to explore the role of family and community
      involvement in school nutrition and physical activity standards. METHODS: Survey
      data on nutrition and physical activity policies, as well as family and community
      involvement, were available for 28 states, representing 6732 secondary schools.
      One-factor analysis of variance (ANOVA), 2-sample t-tests, Pearson's chi-square
      tests, and multiple logistic and linear regression models were employed in this
      analysis. RESULTS: Family and community involvement were associated with schools
      more frequently utilizing healthy eating strategies and offering students
      healthier food options. Further, involvement was associated with greater support
      for physical education staff and more intramural sports opportunities for
      students. CONCLUSIONS: Though family and community involvement have the potential
      to have a positive influence on school nutrition and physical activity policies
      and practices, involvement remains low in schools. Increased efforts are needed
      to encourage collaboration among schools, families, and communities to ensure the
      highest health standards for all students.

PMID- 25564978
TI  - Rural middle school nutrition and physical activity environments and the change
      in body mass index during adolescence.
AB  - BACKGROUND: For rural adolescents, schools are among the few places where
      environmental interventions can promote health outside of the home. The goal of
      this study was to assess the nutrition and physical activity (N&PA) environments
      of schools attended by a birth cohort and examine the association with change in
      body mass index (BMI) from sixth to eighth grade. METHODS: Using data from
      adolescents of a rural New York State birth cohort (N = 281), we used linear
      mixed models to identify N&PA environments associated with change in BMI. We also
      examined family income trajectory as a potential modifier to consider how the
      association between school environment and change in BMI might differ depending
      on income. RESULTS: We found considerable heterogeneity in environments within
      and between schools. Among students with low-income trajectories, reductions in
      BMI z-scores were associated with school environments that promote better
      physical education (PE) and general (non-PE, non-sport) physical activity.
      Schools with better sports environments were associated with reductions in BMI
      for some students, but not lower-income students. CONCLUSIONS: School
      environments may have differing effects on students depending on their
      socioeconomic status. Strategies are needed to identify and address barriers that
      impair low-income students' access to health-promoting school resources.

PMID- 25564979
TI  - Coping styles of adolescents experiencing multiple forms of discrimination and
      bullying: evidence from a sample of ethnically diverse urban youth.
AB  - BACKGROUND: We used a latent class analysis (LCA) to characterize coping styles
      of urban youth and examined if coping styles moderated the association between
      experiencing discrimination and bullying and depressive symptoms. METHODS: The
      data come from the 2006 Boston Youth Survey, where students were asked to select
      2 behaviors they do most often when they are upset, from a list of 15 options. A
      total of 927 (75%) students contributed to the LCA analytic sample (44% non
      Hispanic Blacks, 29% Hispanics, and 58% girls). Relative and absolute fit indices
      determined the number of classes. An interaction term between types of
      discrimination and bullying experienced and coping style tested for moderation.
      RESULTS: The LCA revealed that a 3-class solution had the best fit (Lo-Mendell
      Rubin likelihood ratio test, 4-class vs 3-class, p-value .12). The largest coping
      style class was characterized by high endorsement of distractive coping
      strategies (59%), the second class was characterized by using supportive coping
      strategies (27%), and the third class was characterized by using avoidance coping
      strategies (12%). We found a significant interaction between discrimination and
      coping style for depressive symptoms. CONCLUSIONS: The relationship between
      experiencing discrimination and depression varied based on coping style and the
      type of discrimination and bullying experienced.

PMID- 25564980
TI  - Salty or sweet? Nutritional quality, consumption, and cost of snacks served in
      afterschool programs.
AB  - BACKGROUND: Snacks served in afterschool programs (ASPs, 3-6 pm) represent an
      important opportunity to promote healthy eating. ASP policies suggest a
      fruit/vegetable is served daily, while sugar-sweetened foods/beverages and
      artificially flavored snacks are eliminated. Limited information exists on the
      types of snacks served in ASPs, if snacks meet existing nutrition policies,
      whether children eat the snacks, and their cost. METHODS: Direct observation of
      snacks served and consumed was collected in 20 ASPs serving over 1700 elementary
      age children. The number of days that snacks were served/week was evaluated for
      compliance with nutrition policies. Costs of snacks were collected via receipts.
      RESULTS: Programs served desserts and artificially flavored salty snacks on 2.7
      and 2.1 days/week. Fruits and vegetables were served 0.6 and 0.1 days/week,
      respectively. Sugar-sweetened beverages were served 1.8 days/week. Of the
      children (N = 383) observed, 75% to 100% consumed the snack served, with 95% and
      100% of served fruits/vegetables consumed. No ASP served fruit/vegetables daily,
      18 served sugar-sweetened foods, 16 served artificially flavored snacks, and 14
      served sugar-sweetened beverages. Desserts and salty snacks cost $0.27
      $0.32/snack vs $0.38-$0.40/snack for vegetables/fruits. CONCLUSIONS: The quality
      of snacks failed to meet nutrition policies and consists of predominately high
      sugar and artificially flavored options. Strategies to improve snack offerings in
      ASPs while addressing price barriers are required.

PMID- 25564981
TI  - Effectiveness of school-initiated physical activity program on secondary school
      students' physical activity participation.
AB  - BACKGROUND: The promotion of physical activity and health has become a universal
      challenge. The Sotkamo Physical Activity as Civil Skill Program was implemented
      to increase students' physical activity by promoting supportive psychological and
      physical school environment. The aim of this study was to evaluate the
      effectiveness of the school-initiated physical activity program on secondary
      school students' self-reported physical activity. METHODS: The sample included
      847 students (experimental condition school = 208, control school = 639) at the
      age of 12 to 14 years from northeast and central Finland. The program was
      conducted across 1 academic year and 2 measurement phases were carried out using
      self-report questionnaires in April 2011 and 2012. RESULTS: The findings
      highlighted that the program appeared to be effective as an approach to change
      the sharp decline in the pattern of Grade 7 students' self-reported physical
      activity across 1 school year. Specifically, change in the experimental condition
      students' self-reported physical activity was 13.4% higher compared the students
      in the control condition. CONCLUSION: On the basis of current findings, increased
      opportunities for school day physical activities have the potential to affect
      large number of students and are an efficient strategy for promoting regular
      physical activity.

PMID- 25564982
TI  - A multicomponent school-based asthma management program: enhancing connections to
      clinical care.

PMID- 25564983
TI  - Serum autoantibodies in silicosis and non-silicosis cement workers.
AB  - AIM: To study serum autoantibodies and immunoglobulin levels in cement workers.
      METHODS: Blood samples for numerous antibodies were collected from 30 silicosis
      and 42 non-silicosis cement workers. Spirometry of the silicosis workers was also
      studied. RESULTS: Serum IgA mean level showed a significant increase in the
      silicosis group compared to the non-silicosis group. Elevated titers of serum
      anti-smooth muscle antibodies (ASMA) and anti-glomerular basement membrane (anti
      GBM) were detected only in the silicosis group. The duration of exposure showed a
      significant positive correlation with serum IgA, ASMA and anti-GBM, and a
      significant negative correlation with serum IgG. Serum anti-GBM showed a
      significant positive correlation with IgG while the inverse titer (1/titer) of
      anti-GBM showed highly significant positive correlations with serum IgA and ASMA.
      The percent predicted FVC was the ventilatory function most closely associated
      with immunological parameters in silicosis group. CONCLUSION: Serum IgA, ASMA,
      and anti-GBM are the principal immunologic parameters associated with silicosis.

PMID- 25564984
TI  - Long-term adaptive response to high-frequency light signals in the unicellular
      photosynthetic eukaryote Dunaliella salina.
AB  - Productivity of microalgal cultivation processes is tightly related to
      photosynthetic efficiency, and therefore to light availability at the cell scale.
      In an agitated, highly turbid suspension,the light signal received by a single
      phytoplankton cell moving in a dense culture is a succession of flashes. The
      growth characteristics of microalgae under such dynamic light conditions are thus
      fundamental information to understand nonlinear properties of the photosynthetic
      process and to improve cultivation process design and operation. Studies of the
      long term consequences of dynamic illumination regime on photosynthesis require a
      very specific experimental set-up where fast varying signals are applied on the
      long term. In order to investigate the growth response of the unicellular
      photosynthetic eukaryote Dunaliella salina (Chlorophyceae) to intermittent light
      exposure, different light regimes using LEDs with the same average total light
      dose were applied in continuous cultures. Flashing light with different durations
      of light flashes (?t of 30 s, 15 s, 2 s and 0.1 s) followed by dark periods of
      variable length (0.67 <= L:D <= 2) yielding flash frequencies in the range 0.017
      5 Hz, were compared to continuous illumination. Specific growth rate,
      photosynthetic pigments, lipid productivity and elemental composition were
      measured on two duplicates for each irradiance condition. The different
      treatments of intermittent light led to specific growth rates ranging from 0.25
      to 0.93 day(-1) . While photosynthetic efficiency was enhanced with increased
      flash frequency, no significant differences were observed in the particular
      carbon and chlorophyll content. Pigment analysis showed that within this range of
      flash frequency, cells progressively photoacclimated to the average light
      intensity.

PMID- 25564985
TI  - Photoelectron spectrum and dynamics of the uracil cation.
AB  - The photoelectron spectrum of uracil and the molecular dynamics of its radical
      cation are investigated using the multiconfigurational time-dependent Hartree
      (MCTDH) method. For this aim, the vibronic coupling model Hamiltonian is used
      including up to ten important a' modes. Moreover, to account for coupling through
      conical intersections between states of different symmetry in the system,
      coupling constants of two a" modes are taken into account. The parameters used in
      the model are obtained by fitting to ab inito data obtained with extensive EOM-IP
      CCSD calculations. The first four cationic states were investigated, which are
      either of A" (hole in a pi orbital) or A' (hole in a nO orbital) symmetry. The
      results of the wavepacket propagations were used to calculate the corresponding
      photoelectron spectrum and compare to the experimental spectrum. The MCTDH
      simulations reproduce the experimental spectrum well. The dynamics starting from
      the D2 and D3 ionic states show a fast relaxation to the cationic ground state
      often involving direct D2-D0 or D3-D1 transitions. 

PMID- 25564987
TI  - Lysophosphatidic acid improves porcine oocyte maturation and embryo development
      in vitro.
AB  - Lysophosphatidic acid (LPA), a member of the phospholipid autacoid family, is
      present in human follicular fluid. The aim of the present study was to compare
      the developmental competence of porcine embryos created via in vitro
      fertilization (IVF) and parthenogenetic activation (PA) in culture medium
      supplemented with LPA, in comparison with a control group. The effects of LPA on
      porcine oocyte maturation and pre-implantation embryonic development were also
      examined. Addition of 10 MUM LPA to the oocyte maturation medium significantly
      increased the proportion of oocytes reaching metaphase I (MI) or metaphase II
      (MII), and enhanced embryonic developmental potential. When present during oocyte
      maturation, LPA significantly increased the abundance of phosphorylated ERK1/2 in
      MI and MII oocytes, showing that LPA enhanced nuclear maturation via activation
      of the mitogen-activated protein kinase (MAPK) pathway. In addition, Cyclin B1
      levels were elevated in MI- and MII-stage oocytes, suggesting that LPA plays a
      role in both nuclear and cytoplasmic maturation of oocytes. After fertilization,
      the frequency of polyspermy in embryos obtained using LPA-treated oocytes was
      less than that in the control group. Further, blastocyst formation and blastocyst
      cell number were enhanced and apoptosis was reduced upon LPA treatment of embryos
      created either by IVF and PA. LPA treatment of blastocysts derived by IVF or PA
      resulted in increased expression of the anti-apoptotic BCL2L1 gene while reducing
      expression of the pro-apoptotic genes BAX and CASP3. Together, our data indicate
      that LPA supplementation improves porcine oocyte maturation and subsequent in
      vitro development of pre-implantation embryos.

PMID- 25564986
TI  - Economic hardship of minority and non-minority cancer survivors 1 year after
      diagnosis: another long-term effect of cancer?
AB  - BACKGROUND: Current literature suggests that racial/ethnic minority survivors may
      be more likely than whites to experience economic hardship after a cancer
      diagnosis; however, little is known about such hardship. METHODS: Patients with
      lung cancer (LC) and colorectal cancer (CRC) participating in the Cancer Care
      Outcomes Research and Surveillance (CanCORS) Consortium were surveyed
      approximately 4 months (baseline) and 12 months (follow-up) after diagnosis.
      Economic hardship at follow-up was present if participants 1) indicated
      difficulty living on household income; and/or 2) for the following 2 months,
      anticipated experiencing hardships (inadequate housing, food, or medical
      attention) or reducing living standards to the bare necessities of life. The
      authors tested whether African Americans (AAs) and Hispanics were more likely
      than whites to experience economic hardship controlling for sex, age, education,
      marital status, cancer stage, treatment, and economic status at baseline (income,
      prescription drug coverage). RESULTS: Of 3432 survivors (39.7% with LC, 60.3%
      with CRC), 14% were AA, 7% were Hispanic, and 79% were white. AAs and Hispanics
      had lower education and income than whites. Approximately 68% of AAs, 58% of
      Hispanics, and 44.5% of whites reported economic hardship. In LC survivors, the
      Hispanic-white disparity was not significant in unadjusted or adjusted analyses,
      and the AA-white disparity was explained by baseline economic status. In CRC
      survivors, the Hispanic-white disparity was explained by baseline economic
      status, and the AA-white disparity was not explained by the variables that were
      included in the model. CONCLUSIONS: Economic hardship was evident in almost 1 in
      2 cancer survivors 1 year after diagnosis, especially AAs. Research should
      evaluate and address risk factors and their impact on survival and survivorship
      outcomes.

PMID- 25564988
TI  - Effect of biotic and abiotic stresses on volatile emission of Achillea collina
      Becker ex Rchb.
AB  - This study describes the application of headspace solid-phase microextraction (HS
      SPME)-gas chromatography/mass spectrometry (GC/MS) to characterise the volatile
      fingerprint changes of Achillea collina, induced by aphids' infestation,
      mechanical damage and jasmonic acid (JA) treatment. The volatile organic compound
      profiles of A. collina, Prunus persica and Pisum sativum infested by Myzus
      persicae were also compared. Several changes were observed between control,
      infested, mechanically damaged and JA-treated plants, and new inducible volatile
      organic compounds (IVOCs) were emitted in response to biotic or abiotic stresses.
      Some of these were in common for all stresses and other compounds were in common
      only for two types of stress. Conversely some IVOCs were emitted only in response
      to the specific stimuli. The results suggested that there were species-specific
      and common IVOCs emitted by A. collina, P. persica and P. sativum in response to
      M. persicae infestation. In conclusion, HS-SPME-GC/MS seems to be a reliable
      analytical approach to study in vivo plant reaction to external stimuli.

PMID- 25564989
TI  - Correction to "Proteome-Wide Discovery of Unknown ATP-Binding Proteins and Kinase
      Inhibitor Target Proteins Using an ATP Probe".

PMID- 25564990
TI  - Structural characterization of a degradation product of rocuronium using
      nanoelectrospray-high resolution mass spectrometry.
AB  - Rocuronium bromide is a non-depolarizing neuromuscular blocking agent that causes
      rapid muscle relaxation after intravenous injection. Regulatory authorities for
      registration of pharmaceuticals for human use require the evaluation of the
      stability of active compounds under various stress conditions. Forced degradation
      of rocuronium bromide was performed under hydrolytic, thermal, photolytic, and
      oxidative settings. HPLC-UV/vis analysis revealed an unknown degradation product
      under oxidative conditions (1% H2 O2 , reflux for 1 h). Investigation of the
      respective HPLC fraction by high resolution mass spectrometry indicated a formal
      loss of CH2 and an addition of one oxygen atom to the intact drug molecule.
      Additional multistage mass spectrometric structural elucidation experiments aided
      by complementary information from analysis of the intact drug and known
      rocuronium-related compounds showed that the morpholine moiety was unstable under
      oxidative stress. The data demonstrated that the morpholine ring was opened and
      transformed to an N-ethanoyl-formamide group. The structure was supported by
      appropriate mechanistic explanations.

PMID- 25564992
TI  - Copper-catalyzed one-pot synthesis of 1,2,4-triazoles from nitriles and
      hydroxylamine.
AB  - A simple and efficient copper-catalyzed one-pot synthesis of substituted 1,2,4
      triazoles through reactions of two nitriles with hydroxylamine has been
      developed. The protocol uses simple and readily available nitriles and
      hydroxylamine hydrochloride as the starting materials and inexpensive Cu(OAc)2 as
      the catalyst, and the corresponding 1,2,4-triazole derivatives are obtained in
      moderate to good yields. The reactions include sequential intermolecular addition
      of hydroxylamine to one nitrile to provide amidoxime, copper-catalyzed treatment
      of the amidoxime with another nitrile, and intramolecular
      dehydration/cyclization. This finding provides a new and useful strategy for
      synthesis of 1,2,4-triazole derivatives. 

PMID- 25564991
TI  - Fullerene-associated phenanthrene contributes to bioaccumulation but is not toxic
      to fish.
AB  - The present study investigated the effects of aqueous fullerene suspensions (nC60
      ) on the bioavailability and toxicity of phenanthrene (Phe) to junior carp
      (Cyprinus carpio). Bioaccumulation factors (BAFs) were calculated based on total
      as well as free concentrations of Phe. Equal BAF values were obtained with and
      without nC60 based on the total concentrations, whereas greater BAFs were found
      in the presence of nC60 when free Phe concentrations were applied. The results
      demonstrated that nC60 could act as a contaminant carrier to facilitate Phe
      bioaccumulation. The concentration-response relationship of induced hepatic 7
      ethoxysorufin-O-deethylase activity was established in regard to the total and
      free concentrations of aqueous Phe solutions as well as the body residues. The
      concentration-response curves were reliant on the nC60 concentration when the
      total concentration of Phe was employed as a variable but were independent of
      nC60 presence when free concentration or body residue was employed as a variable,
      implying that the latter 2 parameters were more accurate in evaluating biological
      effects. Particles of C60 were mostly distributed in fish liver and intestines,
      which indicated the primary routine of uptake was through ingestion.
      Approximately 22% to 100% of the Phe-nC60 complex contributed to the
      bioaccumulation, whereas the complex did not contribute to the toxicity.

PMID- 25564993
TI  - Outcome of inotropic therapy: is less always more?
AB  - PURPOSE OF REVIEW: Positive inotropic agents are widely used in the management of
      the critical ill patient presenting with low cardiac output state. Different
      inotropic agents are available, and different effects on hemodynamic endpoints
      may be recognized, but data on relevant clinical endpoints are scarce. A growing
      body of literature suggests that overuse of inotropes may have detrimental
      effects on cardiomyocytes, resulting in an increased risk of morbidity and
      mortality. The present review will summarize recent literature, focusing on
      outcome studies among adult patients related to use of inotropes in different
      clinical settings. RECENT FINDINGS: Use of inotropic therapy shows a manifold
      variation between hospitals and individual providers even after risk
      standardization. No recent studies have shown inotropic therapy to provide short
      term and long-term improvement of morbidity and mortality in patients with
      advanced nonsurgical heart failure or septic shock or as part of goal-directed
      treatment in high-risk noncardiac surgery. Levosimendan may show beneficial
      effect on mortality in cardiac surgery. CONCLUSION: A 'less is more' approach may
      show to be appropriate when relating to routine use of inotropes. Inotropic
      therapy should be restricted to patients with heart failure and clinical signs of
      end-organ hypoperfusion.

PMID- 25564994
TI  - Effect of basic and acidic additives on the separation of some basic drug
      enantiomers on polysaccharide-based chiral columns with acetonitrile as mobile
      phase.
AB  - The separation of enantiomers of 16 basic drugs was studied using polysaccharide
      based chiral selectors and acetonitrile as mobile phase with emphasis on the role
      of basic and acidic additives on the separation and elution order of enantiomers.
      Out of the studied chiral selectors, amylose phenylcarbamate-based ones more
      often showed a chiral recognition ability compared to cellulose phenylcarbamate
      derivatives. An interesting effect was observed with formic acid as additive on
      enantiomer resolution and enantiomer elution order for some basic drugs. Thus,
      for instance, the enantioseparation of several beta-blockers (atenolol, sotalol,
      toliprolol) improved not only by the addition of a more conventional basic
      additive to the mobile phase, but also by the addition of an acidic additive.
      Moreover, an opposite elution order of enantiomers was observed depending on the
      nature of the additive (basic or acidic) in the mobile phase.

PMID- 25564995
TI  - Training Public Health Advisors.
AB  - Federal public health advisors provide guidance and assistance to health
      departments to improve public health program work. The Centers for Disease
      Control and Prevention (CDC) prepares them with specialized training in
      administering public health programs. This article describes the evolving
      training and is based on internal CDC documents and interviews. The first federal
      public health advisors worked in health departments to assist with controlling
      syphilis after World War II. Over time, more CDC prevention programs hired them.
      To meet emerging needs, 3 major changes occurred: the Public Health Prevention
      Service, a fellowship program, in 1999; the Public Health Associate Program in
      2007; and integration of those programs. Key components of the updated training
      are competency-based training, field experience, supervision, recruitment and
      retention, and stakeholder support. The enduring strength of the training has
      been the experience in a public health agency developing practical skills for
      program implementation and management.

PMID- 25564996
TI  - GATA-binding protein 3 enhances the utility of gross cystic disease fluid protein
      15 and mammaglobin A in triple-negative breast cancer by immunohistochemistry.
AB  - AIMS: We have demonstrated previously that gross cystic disease fluid protein-15
      (GCDFP-15) and mammaglobin A (MAM) are of limited utility in triple-negative
      breast cancer (TNBC). GATA-binding protein 3 (GATA-3) is an emerging breast
      associated immunohistochemical (IHC) marker with limited data in TNBC. Here, we
      examined GATA-3 expression in TNBC in comparison with GCDFP-15 and MAM. METHODS
      AND RESULTS: We studied GATA-3, GCDFP-15 and MAM IHC expression in 62 primary and
      68 metastatic TNBCs. In primary TNBCs, GATA-3 staining was observed in 25 cases
      (40%), including 16 cases that were negative for GCDFP-15 and MAM. In metastatic
      TNBCs, GATA-3 staining was observed in 30 cases (44%), including 16 cases that
      were negative for GCDFP-15 and MAM. The expression frequency of any of the
      markers was 56% in primary and 62% in metastatic TNBCs. However, when focal
      staining was excluded, the expression frequency of any marker dropped to 31% and
      44%, respectively. CONCLUSION: GATA-3 is expressed at a higher frequency by IHC
      in TNBC compared to GCDFP-15 and MAM, although the tissue specificity of the
      latter markers may be superior. When evaluating a triple-negative tumour,
      including GATA-3 in a panel of markers may increase the diagnostic accuracy for
      tissue origin in the appropriate clinical setting.

PMID- 25564997
TI  - Divergent mechanistic routes for the formation of gem-dimethyl groups in the
      biosynthesis of complex polyketides.
AB  - The gem-dimethyl groups in polyketide-derived natural products add steric bulk
      and, accordingly, lend increased stability to medicinal compounds, however, our
      ability to rationally incorporate this functional group in modified natural
      products is limited. In order to characterize the mechanism of gem-dimethyl group
      formation, with a goal toward engineering of novel compounds containing this
      moiety, the gem-dimethyl group producing polyketide synthase (PKS) modules of
      yersiniabactin and epothilone were characterized using mass spectrometry. The
      work demonstrated, contrary to the canonical understanding of reaction order in
      PKSs, that methylation can precede condensation in gem-dimethyl group producing
      PKS modules. Experiments showed that both PKSs are able to use dimethylmalonyl
      acyl carrier protein (ACP) as an extender unit. Interestingly, for epothilone
      module 8, use of dimethylmalonyl-ACP appeared to be the sole route to form a gem
      dimethylated product, while the yersiniabactin PKS could methylate before or
      after ketosynthase condensation. 

PMID- 25564998
TI  - Effects of blood flow restriction duration on muscle activation and microvascular
      oxygenation during low-volume isometric exercise.
AB  - The purpose of the investigation was to observe how varying occlusion durations
      affected neuromuscular activation and microvascular oxygenation during low-volume
      isometric knee extension exercise. Healthy, recreationally active males performed
      isometric knee extension at a variety of submaximal intensities under different
      blood flow restriction (BFR) occlusion durations. The occlusion pressure (130%
      SBP) was applied either 5 min prior to exercise (PO), immediately prior to
      exercise (IO) or not during exercise (CON). Surface electromyography (sEMG) and
      near-infrared spectroscopy (NIRS) was used to record the neuromuscular activation
      and microvascular oxygenation of the knee extensors during exercise. No
      difference in sEMG was observed in the vastus lateralis or vastus medialis during
      any exercise condition or any submaximal intensity. PO elicited greater
      microvascular deoxygenation (deoxy-[Hb + Mb]) compared to CON (P<=0.05) at all
      submaximal intensities and also compared to IO at 20% maximal voluntary
      contraction (MVC). IO resulted in a greater deoxy-[Hb + Mb] response during low
      intensity exercise (20% and 40% MVC) compared to CON (P<=0.05). These findings
      suggest that applying BFR 5 min before exercise can enhance the exercise-induced
      metabolic stress (i.e. deoxy-[Hb + Mb]), measured via NIRS, during low-intensity
      exercise (20% MVC) compared to applying BFR immediately prior to exercise.
      Furthermore, the increased metabolic stress observed during IO is attenuated
      during high-intensity (60% MVC, 80% MVC) exercise when compared to CON
      conditions. Knowledge of the changes in exercise-induced metabolic stress between
      the various occlusion durations may assist in developing efficient BFR exercise
      programmes. 

PMID- 25565000
TI  - Effects of surface passivation on twin-free GaAs nanosheets.
AB  - Unlike nanowires, GaAs nanosheets exhibit no twin defects, stacking faults, or
      dislocations even when grown on lattice mismatched substrates. As such, they are
      excellent candidates for optoelectronic applications, including LEDs and solar
      cells. We report substantial enhancements in the photoluminescence efficiency and
      the lifetime of passivated GaAs nanosheets produced using the selected area
      growth (SAG) method with metal organic chemical vapor deposition (MOCVD).
      Measurements are performed on individual GaAs nanosheets with and without an
      AlGaAs passivation layer. Both steady-state photoluminescence and time-resolved
      photoluminescence spectroscopy are performed to study the optoelectronic
      performance of these nanostructures. Our results show that AlGaAs passivation of
      GaAs nanosheets leads to a 30- to 40-fold enhancement in the photoluminescence
      intensity. The photoluminescence lifetime increases from less than 30 to 300 ps
      with passivation, indicating an order of magnitude improvement in the minority
      carrier lifetime. We attribute these enhancements to the reduction of
      nonradiative recombination due to the compensation of surface states after
      passivation. The surface recombination velocity decreases from an initial value
      of 2.5 * 10(5) to 2.7 * 10(4) cm/s with passivation. 

PMID- 25564999
TI  - Regulation of B lymphocyte responses to Toll-like receptor ligand binding during
      diabetes prevention in non-obese diabetic (NOD) mice.
AB  - BACKGROUND: Interactions between genetic risk factors and the environment drive
      type 1 diabetes (T1D). The system of Toll-like receptors (TLR) detects these
      environmental triggers; however, the target cell that intermediates these
      interactions to drive T1D remains unknown. METHODS: We investigated the effect of
      TLR pathway activation (myeloid differentiation primary response 88 [MyD88] vs
      TIR-domain-containing adapter-inducing interferon-beta [TRIF]) on B cell subsets
      via flow cytometry, including their activation, survival, proliferation, and
      cytoskeletal mobilization. The effect of polyinosinic-polycytidylic acid
      (poly(I:C)) on diabetes development was addressed, including the B cell-dependent
      activation of diabetes-protective DX5+ cells, using genetic models and adoptive
      transfer. RESULTS: B lymphocytes from non-obese diabetic (NOD) mice expressed
      enhanced levels of TLR-responsive proteins. Ex vivo analysis of B lymphocyte
      subsets demonstrated that TLR3 stimulation via TRIF deletes cells exhibiting a
      marginal zone phenotype, whereas MyD88-dependent ligands enhance their survival.
      In vivo, marginal zone B cells were activated by poly(I:C) and were unexpectedly
      retained in the spleen of NOD mice, in contrast with the mobilization of these
      cells in non-autoimmune mice, a phenotype we traced to defective actin
      cytoskeletal dynamics. These activated B cells mediated TLR3-induced diabetes
      protection. CONCLUSIONS: Immunotherapies must account for both B cell location
      and activation, and these properties may differ in autoimmune and healthy
      settings.

PMID- 25565001
TI  - IMAGING DIAGNOSIS-THROMBOSED ORBITAL VARIX IN A DOG.
AB  - A 9-week-old female Rhodesian Ridgeback presented with exophthalmos following
      minor blunt trauma to the left orbital area. Ocular ultrasound showed an
      extraconal retrobulbar mass ventromedial to the left globe. Magnetic resonance
      (MR) imaging demonstrated a thrombosed orbital vascular malformation without
      intracranial extension. Doppler ultrasound features of nonpulsatile slow flow
      were consistent with an orbital varix. Contrast-enhanced dynamic time-resolved
      and high-resolution MR angiography demonstrated the varix arose from the
      anastomotic branch of the dorsal and ventral external ophthalmic veins.
      Conservative management led to a positive outcome defined as a visual eye and
      nearly normal cosmetic appearance at 8-month follow-up. 

PMID- 25565003
TI  - Molecular hot electroluminescence due to strongly enhanced spontaneous emission
      rates in a plasmonic nanocavity.
AB  - We have recently demonstrated anomalous relaxationless hot electroluminescence
      from molecules in the tunnel junction of a scanning tunneling microscope [Dong et
      al., Nat. Photonics, 2010, 4, 50]. In the present paper, based on physically
      realistic parameters, we aim to unravel the underlying physical mechanism using a
      multiscale modeling approach that combines classical generalized Mie theory with
      the quantum master equation. We find that the nanocavity-plasmon-tuned
      spontaneous emission rate plays a crucial role in shaping the spectral profile.
      In particular, on resonance, the radiative decay rate can be enhanced by three-to
      five orders of magnitude, which enables the radiative process to occur on the
      lifetime scale of picoseconds and become competitive to the vibrational
      relaxation. Such a large Purcell effect opens up new emission channels to
      generate the hot luminescence that arises directly from higher vibronic levels of
      the molecular excited state. We also stress that the critical role of resonant
      plasmonic nanocavities in tunneling electron induced molecular luminescence is to
      enhance the spontaneous radiative decay through plasmon enhanced vacuum
      fluctuations rather than to generate an efficient plasmon stimulated emission
      process. This improved understanding has been partly overlooked in previous
      studies but is believed to be very important for further developments of
      molecular plasmonics and optoelectronics. 

PMID- 25565002
TI  - Longitudinal analysis of maternal serum Follistatin concentration in normal
      pregnancy and preeclampsia.
AB  - OBJECTIVE: Follistatin (FST) is a regulator of the biological activity of activin
      A (Act A), binding and blocking it, which could contribute to the modulation of
      its pro-inflammatory activity during pregnancy. We sought to investigate, in this
      nested case-control study, FST serum levels during normal pregnancy and correlate
      it with the FST profile in preeclamptic pregnant women, normal pregnant women
      followed 3 months postpartum and eumenorrheic nonpregnant women throughout the
      menstrual cycle. SUBJECTS AND METHODS: Follistatin serum levels determined by
      ELISA, biochemical and anthropometric variables were measured in normal pregnant
      (n = 28) and preeclamptic (n = 20) women during three periods of gestation. In
      addition, FST serum levels were measured in a subset of normal pregnant women (n
      = 13) followed 3 months postpartum and in eumenorrheic nonpregnant women (n = 20)
      during the follicular and luteal phases of the menstrual cycle. RESULTS:
      Follistatin serum levels in the eumenorrheic nonpregnant and postpartum group
      were significantly lower when compared to levels throughout gestation (P < 0.01).
      Serum FST levels increased in each period of pregnancy analysed, being
      significantly higher towards the end of gestation (P < 0.01). FST levels were
      lower in late pregnancy in preeclamptic women compared to normal pregnant women
      (P < 0.05). Finally, FST levels were higher in the luteal phase when compared
      with the follicular phase of the menstrual cycle (P < 0.05). CONCLUSIONS: These
      analyses would permit the consideration that changes in FST levels during
      pregnancy contribute to the control of the Act A system.

PMID- 25565004
TI  - Bioaccumulation, biotransformation, and toxicity of BDE-47, 6-OH-BDE-47, and 6
      MeO-BDE-47 in early life-stages of zebrafish (Danio rerio).
AB  - 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), 6-hydroxy-tetrabromodiphenyl ether
      (6-OH-BDE-47), and 6-methoxy-tetrabromodiphenyl ether (6-MeO-BDE-47) are the most
      detected congeners of polybrominated diphenyl ethers (PBDEs), OH-BDEs, and MeO
      BDEs, respectively, in aquatic organisms. Although it has been demonstrated that
      BDE-47 can interfere with certain endocrine functions that are mediated through
      several nuclear hormone receptors (NRs), most of these findings were from
      mammalian cell lines exposed in vitro. In the present study, embryos and larvae
      of zebrafish were exposed to BDE-47, 6-OH-BDE-47, and 6-MeO-BDE-47 to compare
      their accumulation, biotransformation, and bioconcentration factors (BCF) from 4
      to 120 hpf. In addition, effects on expression of genes associated with eight
      different pathways regulated by NRs were investigated at 120 hpf. 6-MeO-BDE-47
      was most bioaccumulated and 6-OH-BDE-47, which was the most potent BDE, was least
      bioaccumulated. Moreover, the amount of 6-MeO-BDE-47, but not BDE-47, transformed
      to 6-OH-BDE-47 increased in a time-dependent manner, approximately 0.01%, 0.04%,
      and 0.08% at 48, 96, and 120 hpf, respectively. Expression of genes regulated by
      the aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and
      mineralocorticoid receptor (MR) was affected in larvae exposed to 6-OH-BDE-47,
      whereas genes regulated by AhR, ER, and the glucocorticoid receptor (GR) were
      altered in larvae exposed to BDE-47. The greatest effect on expression of genes
      was observed in larvae exposed to 6-MeO-BDE-47. Specifically, 6-MeO-BDE-47
      affected the expression of genes regulated by AhR, ER, AR, GR, and thyroid
      hormone receptor alpha (TRalpha). These pathways were mostly down-regulated at
      2.5 MUM. Taken together, these results demonstrate the importance of usage of an
      internal dose to assess the toxic effects of PBDEs. BDE-47 and its analogs
      elicited distinct effects on expression of genes of different hormone receptor
      mediated pathways, which have expanded the knowledge of different mechanisms of
      endocrine disrupting effects in aquatic vertebrates. Because some of these
      homologues are natural products, assessments of risks of anthropogenic PBDE need
      to be made against the background of concentrations from naturally occurring
      products. Even though PBDEs are being phased out as flame retardants, the natural
      products remain. 

PMID- 25565006
TI  - Fan-shaped gold nanoantennas above reflective substrates for surface-enhanced
      infrared absorption (SEIRA).
AB  - Here, we report a new nanoantenna for surface-enhanced infrared absorption
      (SEIRA) detection, consisting of a fan-shaped Au structure positioned at a well
      specified distance above a reflective plane with an intervening silica spacer
      layer. We examine how to optimize both the antenna dimensions and the spacer
      layer for optimal SEIRA enhancement of the C-H stretching mode. This tunable 3D
      geometry yields a theoretical SEIRA enhancement factor of 10(5), corresponding to
      the experimental detection of 20-200 zeptomoles of octadecanethiol, using a
      standard commercial FTIR spectrometer. Experimental studies illustrate the
      sensitivity of the observed SEIRA signal to the gap dimensions. The optimized
      antenna structure exhibits an order of magnitude greater SEIRA sensitivity than
      previous record-setting designs. 

PMID- 25565008
TI  - From Discovery to Function: The Expanding Roles of Long Non-Coding RNAs in
      Physiology and Disease.
AB  - Long non-coding RNAs (lncRNAs) are a relatively poorly understood class of RNAs
      with little or no coding capacity transcribed from a set of incompletely
      annotated genes. They have received considerable attention in the past few years
      and are emerging as potentially important players in biological regulation. Here
      we discuss the evolving understanding of this new class of molecular regulators
      that has emerged from ongoing research, which continues to expand our databases
      of annotated lncRNAs and provide new insights into their physical properties,
      molecular mechanisms of action, and biological functions. We outline the current
      strategies and approaches that have been employed to identify and characterize
      lncRNAs, which have been instrumental in revealing their multi-faceted roles
      ranging from cis- to trans-regulation of gene expression, and from epigenetic
      modulation in the nucleus to post-transcriptional control in the cytoplasm. In
      addition, we highlight the molecular and biological functions of some of the best
      characterized lncRNA in physiology and disease, especially those relevant to
      endocrinology, reproduction, metabolism, immunology, neurobiology, muscle
      biology, and cancer. Finally, we discuss the tremendous diagnostic and
      therapeutic potential of lncRNAs in cancer and other diseases.

PMID- 25565007
TI  - Digital immunohistochemistry platform for the staining variation monitoring based
      on integration of image and statistical analyses with laboratory information
      system.
AB  - BACKGROUND: Digital immunohistochemistry (IHC) is one of the most promising
      applications brought by new generation image analysis (IA). While conventional
      IHC staining quality is monitored by semi-quantitative visual evaluation of
      tissue controls, IA may require more sensitive measurement. We designed an
      automated system to digitally monitor IHC multi-tissue controls, based on SQL
      level integration of laboratory information system with image and statistical
      analysis tools. METHODS: Consecutive sections of TMA containing 10 cores of
      breast cancer tissue were used as tissue controls in routine Ki67 IHC testing.
      Ventana slide label barcode ID was sent to the LIS to register the serial section
      sequence. The slides were stained and scanned (Aperio ScanScope XT), IA was
      performed by the Aperio/Leica Colocalization and Genie Classifier/Nuclear
      algorithms. SQL-based integration ensured automated statistical analysis of the
      IA data by the SAS Enterprise Guide project. Factor analysis and plot
      visualizations were performed to explore slide-to-slide variation of the Ki67 IHC
      staining results in the control tissue. RESULTS: Slide-to-slide intra-core IHC
      staining analysis revealed rather significant variation of the variables
      reflecting the sample size, while Brown and Blue Intensity were relatively
      stable. To further investigate this variation, the IA results from the 10 cores
      were aggregated to minimize tissue-related variance. Factor analysis revealed
      association between the variables reflecting the sample size detected by IA and
      Blue Intensity. Since the main feature to be extracted from the tissue controls
      was staining intensity, we further explored the variation of the intensity
      variables in the individual cores. MeanBrownBlue Intensity ((Brown+Blue)/2) and
      DiffBrownBlue Intensity (Brown-Blue) were introduced to better contrast the
      absolute intensity and the colour balance variation in each core; relevant factor
      scores were extracted. Finally, tissue-related factors of IHC staining variance
      were explored in the individual tissue cores. CONCLUSIONS: Our solution enabled
      to monitor staining of IHC multi-tissue controls by the means of IA, followed by
      automated statistical analysis, integrated into the laboratory workflow. We found
      that, even in consecutive serial tissue sections, tissue-related factors affected
      the IHC IA results; meanwhile, less intense blue counterstain was associated with
      less amount of tissue, detected by the IA tools.

PMID- 25565009
TI  - Engineering behaviour change in an epidemic: the epistemology of NIH-funded HIV
      prevention science.
AB  - Social scientific and public health literature on National Institutes of Health
      funded HIV behavioural prevention science often assumes that this body of work
      has a strong biomedical epistemological orientation. We explore this assumption
      by conducting a systematic content analysis of all NIH-funded HIV behavioural
      prevention grants for men who have sex with men between 1989 and 2012. We find
      that while intervention research strongly favours a biomedical orientation,
      research into the antecedents of HIV risk practices favours a sociological,
      interpretive and structural orientation. Thus, with respect to NIH-funded HIV
      prevention science, there exists a major disjunct in the guiding epistemological
      orientations of how scientists understand HIV risk, on the one hand, and how they
      engineer behaviour change in behavioural interventions, on the other. Building on
      the extant literature, we suggest that the cause of this disjunct is probably
      attributable not to an NIH-wide positivist orientation, but to the specific
      standards of evidence used to adjudicate HIV intervention grant awards, including
      randomised controlled trials and other quantitative measures of intervention
      efficacy. 

PMID- 25565005
TI  - ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced
      tumour-initiating potential and IL-7 receptor signalling.
AB  - Early T-cell precursor leukaemia (ETP-ALL) is a high-risk subtype of human
      leukaemia that is poorly understood at the molecular level. Here we report
      translocations targeting the zinc finger E-box-binding transcription factor ZEB2
      as a recurrent genetic lesion in immature/ETP-ALL. Using a conditional gain-of
      function mouse model, we demonstrate that sustained Zeb2 expression initiates T
      cell leukaemia. Moreover, Zeb2-driven mouse leukaemia exhibit some features of
      the human immature/ETP-ALL gene expression signature, as well as an enhanced
      leukaemia-initiation potential and activated Janus kinase (JAK)/signal
      transducers and activators of transcription (STAT) signalling through
      transcriptional activation of IL7R. This study reveals ZEB2 as an oncogene in the
      biology of immature/ETP-ALL and paves the way towards pre-clinical studies of
      novel compounds for the treatment of this aggressive subtype of human T-ALL using
      our Zeb2-driven mouse model. 

PMID- 25565010
TI  - Preliminary results from a crowdsourcing experiment in immunohistochemistry.
AB  - BACKGROUND: Crowdsourcing, i.e., the outsourcing of tasks typically performed by
      a few experts to a large crowd as an open call, has been shown to be reasonably
      effective in many cases, like Wikipedia, the Chess match of Kasparov against the
      world in 1999, and several others. The aim of the present paper is to describe
      the setup of an experimentation of crowdsourcing techniques applied to the
      quantification of immunohistochemistry. METHODS: Fourteen Images from MIB1
      stained breast specimens were first manually counted by a pathologist, then
      submitted to a crowdsourcing platform through a specifically developed
      application. 10 positivity evaluations for each image have been collected and
      summarized using their median. The positivity values have been then compared to
      the gold standard provided by the pathologist by means of Spearman correlation.
      RESULTS: Contributors were in total 28, and evaluated 4.64 images each on
      average. Spearman correlation between gold and crowdsourced positivity
      percentages is 0.946 (p < 0.001). CONCLUSIONS: Aim of the experiment was to
      understand how to use crowdsourcing for an image analysis task that is currently
      time-consuming when done by human experts. Crowdsourced work can be used in
      various ways, in particular statistically agregating data to reduce
      identification errors. However, in this preliminary experimentation we just
      considered the most basic indicator, that is the median positivity percentage,
      which provided overall good results. This method might be more aimed to research
      than routine: when a large number of images are in need of ad-hoc evaluation,
      crowdsourcing may represent a quick answer to the need.

PMID- 25565011
TI  - Arthritis possibly induced and exacerbated by a tumour necrosis factor antagonist
      in a patient with psoriasis vulgaris.

PMID- 25565012
TI  - Role of IL-10 and TGF-beta in melanoma.
AB  - IL-10 and TGF-beta are immunosuppressive cytokines expressed in tumors including
      melanoma and, therefore, deemed major cause for failing antitumor immune
      responses. Re-evaluating their role, we compared their expression by quantitative
      RT-PCR in melanoma and skin of healthy individuals, tested their induction in
      dendritic cells and T cells co-cultured with tumor cells, and their effects on
      the immune cells. Both cytokines as well as their receptors were expressed in
      melanoma at significantly lower levels than in healthy skin. Consequently, the
      expressions of IL-10-responsive SOCS-3 and TGF-beta-responsive Smad-7 were low in
      tumors but high in healthy skin. T cells co-cultured with tumor cells developed
      an anergic state without increased IL-10 or TGF-beta expression. In vitro tumor
      induced immature dendritic cells produced high IL-10 levels and less efficiently
      induced T-cell proliferation. Nonetheless, they could be induced to mature, and
      blocking IL-10 did not alter the capacity of the resulting mature dendritic cells
      to stimulate T cells. Mature dendritic cells co-cultured with tumor cells
      produced increased IL-10 but decreased TGF-beta and more efficiently induced T
      cell proliferation. The lack of correlation of IL-10 and TGF-beta with immune
      deficits in situ and in vitro suggests re-evaluating their roles in cancer. 

PMID- 25565013
TI  - Distally Based Abductor Hallucis Adipomuscular Flap for Forefoot Plantar
      Reconstruction.
AB  - Soft tissue and bone defects of the lower leg, ankle, and heel region often
      require coverage by local or distant flaps. The authors successfully used the
      distally based adipomuscular abductor hallucis flap for the treatment of 7
      patients with soft tissue defect on the plantar forefoot after diabetic ulcer (n
      = 2), excision of melanoma at the medial forefoot (n = 3), and posttraumatic
      defects of the plantar forefoot (n = 2). The size of the defects ranged from 6 to
      36 cm. All defects were covered successfully without major complications. The
      distally based adipomuscular flap from the abductor hallucis muscle provides a
      reliable coverage for small and moderate defects of the plantar and medial
      forefoot. This flap is often preferable to the use of free flaps because the
      surgery is rapidly performed and does not require microsurgical expertise. 

PMID- 25565014
TI  - Diffuse papular eruption.

PMID- 25565015
TI  - Emodin inhibits splenocyte proliferation and inflammation by modulating cytokine
      responses in a mouse model system.
AB  - Emodin, an anthraquinone derivative, was investigated for potential anti
      inflammatory and anti-proliferative effects in vitro. The potential to induce
      these outcomes was assessed using concanavalin A (ConA)-stimulated mouse
      splenocytes. Dose-response studies showed that emodin at 100 uM was not cytotoxic
      to naive cells, and that the same dose caused proliferation to be significantly
      reduced in ConA-stimulated cells. In addition, emodin significantly reduced ConA
      induced nitric oxide (NO) production and the formation/release of TH1 (IL-2,
      IFNgamma, TNFalpha) and TH17 (IL-6 and IL-17) cell cytokines, but induced those
      of TH2 (IL-4) and Treg (IL-10) cells. From the results, it is concluded that
      earlier-reported immunomodulatory effects imparted by emodin may have been
      attributable, in part, to anti-proliferative effects on lymphocytes, as well as a
      shift within the TH1/TH2 and TH17/Treg balance (towards TH2 and Treg). These
      findings, while providing evidence of mechanisms of emodin immunomodulation, are
      also potentially important for sparking studies that ultimately may result in the
      potential use of this agent in preventive and/or corrective strategies against
      autoimmune and other inflammatory diseases. 

PMID- 25565016
TI  - Vanadium pentoxide prevents NK-92MI cell proliferation and IFNgamma secretion
      through sustained JAK3 phosphorylation.
AB  - Vanadium is a major air pollutant with toxic and carcinogenic effects; it also
      exercises immunosuppressive effects on the adaptive immune response. Its effect
      on the innate immune response is poorly explored. The aim of this study was to
      identify if vanadium pentoxide (V2O5) impairs the function of immunoregulatory NK
      cells and to determine possible mechanisms associated with this effect.
      Interleukin-2-independent NK-92MI cells were exposed to different V2O5
      concentrations for 6, 12, or 24 h periods. Cell proliferation was then evaluated
      using CFSE staining, apoptosis by Annexin V binding, and necrosis by 7-AAD
      staining. The release of IL-2, -4, -6, -10, -17A, IFNgamma, and TNFalpha by the
      cells were assessed using a human CBA kit. Expression of CD45, SOCS1, JAK3,
      pJAK3, STAT5, pSTAT5, IL-2R, IL-15R, Fas, and FasL in/on the cells was determined
      by flow cytometry; JAK3 and pJAK3 expression were also evaluated via confocal
      microscopy. The results indicated that V2O5 could inhibit NK-92MI cell
      proliferation and induce cell apoptosis in a dose- and time-related manner. V2O5
      also inhibited IL-2, IL-10, and IFNgamma secretion but mostly only after 24 h of
      exposure and with primarily the higher doses tested. V2O5 had no effect on
      expression of JAK3 and STAT5, but did cause an increase in pJAK3 and appeared to
      lead (trend) to reductions in levels of phosphorylated STAT5. V2O5 increased the
      expression of IL-2R, IL-15R, Fas, and FasL at concentrations above the 50-100 uM
      range. V2O5 had no effect on expression of the CD45 membrane phosphatase, but it
      did cause an increase in the expression of SOCS1. These results indicate that a
      key toxic effect of V2O5 on NK cells is a dysregulation of signaling pathways
      mediated by IL-2. These effects could help to explain the previously-reported
      deleterious effects on innate immune responses of hosts exposed to inhaled V2O5. 

PMID- 25565017
TI  - The Effectiveness of Intensive Interaction, A Systematic Literature Review.
AB  - BACKGROUND: Intensive Interaction is an approach used for communicating with
      people with profound and multiple intellectual disabilities or autism. It has
      gained increased recognition as a helpful technique, but the evidence has not
      been systematically reviewed. METHOD: Computerized and hand searches of the
      literature were conducted using synonyms for 'intellectual disabilities',
      'autism' and 'intensive interaction'. RESULTS: Fifteen quantitative and three
      qualitative papers were identified examining the efficacy of the approach with
      participants across the age range in both educational and residential settings.
      CONCLUSIONS: Studies were limited by the quality of reporting and difficulties
      conducting good quality, ethically sound research with participants with PMID.
      Staff support should be considered in training to aid implementation of
      interventions. Studies attempted to investigate whether Intensive Interaction
      builds social interactions or reduces repetitive or self-injurious behaviour.
      More research needs to be conducted before conclusions can be drawn regarding the
      efficacy of this approach.

PMID- 25565018
TI  - Kinetics of methane hydrate replacement with carbon dioxide and nitrogen gas
      mixture using in situ NMR spectroscopy.
AB  - In this study, the kinetics of methane replacement with carbon dioxide and
      nitrogen gas in methane gas hydrate prepared in porous silica gel matrices has
      been studied by in situ (1)H and (13)C NMR spectroscopy. The replacement process
      was monitored by in situ (1)H NMR spectra, where about 42 mol % of the methane in
      the hydrate cages was replaced in 65 h. Large amounts of free water were not
      observed during the replacement process, indicating a spontaneous replacement
      reaction upon exposing methane hydrate to carbon dioxide and nitrogen gas
      mixture. From in situ (13)C NMR spectra, we confirmed that the replacement ratio
      was slightly higher in small cages, but due to the composition of structure I
      hydrate, the amount of methane evolved from the large cages was larger than that
      of the small cages. Compositional analysis of vapor and hydrate phases was also
      carried out after the replacement reaction ceased. Notably, the composition
      changes in hydrate phases after the replacement reaction would be affected by the
      difference in the chemical potential between the vapor phase and hydrate surface
      rather than a pore size effect. These results suggest that the replacement
      technique provides methane recovery as well as stabilization of the resulting
      carbon dioxide hydrate phase without melting. 

PMID- 25565019
TI  - Liaison between myristoylation and cryptic EF-hand motif confers Ca(2+)
      sensitivity to neuronal calcium sensor-1.
AB  - Many members of the neuronal calcium sensor (NCS) protein family have a striking
      coexistence of two characteristics, that is, N-myristoylation and the cryptic EF
      1 motif. We investigated the rationale behind this correlation in neuronal
      calcium sensor-1 (NCS-1) by restoring Ca(2+) binding ability of the disabled EF-1
      loop by appropriate mutations. The concurrence of canonical EF-1 and N
      myristoylation considerably decreased the overall Ca(2+) affinity, conformational
      flexibility, and functional activation of downstream effecter molecules (i.e.,
      PI4Kbeta). Of a particular note, Ca(2+) induced conformational change (which is
      the first premise for a CaBP to be considered as sensor) is considerably reduced
      in myristoylated proteins in which Ca(2+)-binding to EF-1 is restored. Moreover,
      Ca(2+), which otherwise augments the enzymatic activity of PI4Kbeta (modulated by
      NCS-1), leads to a further decline in the modulated PI4Kbeta activity by
      myristoylated mutants (with canonical EF-1) pointing toward a loss of Ca(2+)
      signaling and specificity at the structural as well as functional levels. This
      study establishes the presence of the strong liaison between myristoylation and
      cryptic EF-1 in NCS-1. Breaking this liaison results in the failure of Ca(2+)
      specific signal transduction to downstream effecter molecules despite Ca(2+)
      binding. Thus, the EF-1 disability is a prerequisite in order to append
      myristoylation signaling while preserving structural robustness and Ca(2+)
      sensitivity/specificity in NCS-1. 

PMID- 25565022
TI  - Physician associates in the United Kingdom.

PMID- 25565020
TI  - Ibrutinib inhibits BTK-driven NF-kappaB p65 activity to overcome bortezomib
      resistance in multiple myeloma.
AB  - Multiple Myeloma (MM) is a haematologic malignancy characterized by the
      accumulation of clonal plasma cells in the bone marrow. Over the last 10-15 y the
      introduction of the proteasome-inhibitor bortezomib has improved MM prognosis,
      however relapse due to bortezomib-resistance is inevitable and the disease, at
      present, remains incurable. To model bortezomib-resistant MM we generated
      bortezomib-resistant MM cell lines (n = 4 ) and utilised primary malignant plasma
      cells from patients relapsing after bortezomib treatment (n = 6 ). We identified
      enhanced Bruton's tyrosine kinase (BTK) activity in bortezomib-resistant MM cells
      and found that inhibition of BTK, either pharmacologically with ibrutinib (0.5
      MUM) or via lenti-viral miRNA-targeted BTK interference, re-sensitized previously
      bortezomib-resistant MM cells to further bortezomib therapy at a physiologically
      relevant concentration (5 nM). Further analysis of pro-survival signaling
      revealed a role for the NF-kappaB p65 subunit in MM bortezomib-resistance, thus a
      combination of BTK and NF-kappaB p65 inhibition, either pharmacologically or via
      further lenti-viral miRNA NF-kappaB p65 interference, also restored sensitivity
      to bortezomib, significantly reducing cell viability (37.5 +/- 6 .9 %, ANOVA P <=
      0 .001). Accordingly, we propose the clinical evaluation of a
      bortezomib/ibrutinib combination therapy, including in patients resistant to
      single-agent bortezomib. 

PMID- 25565023
TI  - The Ebola virus epidemic: Preparation, not panic.
AB  - The largest-ever outbreak and first epidemic of Ebola virus disease is affecting
      several West African countries. Early symptoms of Ebola can mimic those of other
      tropical diseases. In a world of rapid global travel, physician assistants need
      to be capable of identifying patients at greatest risk for developing Ebola.
      Clinicians also should be familiar with associated symptoms, diagnosis, and
      treatment considerations. 

PMID- 25565021
TI  - Hospital-level factors associated with report of physical activity in patients on
      mechanical ventilation across Washington State.
AB  - RATIONALE: Use of physical and/or occupational therapy in the intensive care unit
      (ICU) is safe, feasible, and demonstrates improvements in functional status with
      early administration. Access to physical and/or occupational therapy in the ICU
      is variable, with little known regarding its use in community ICUs. OBJECTIVES:
      Determine what proportion of hospitals across Washington State report use of
      physical activity in mechanically ventilated patients and investigate process of
      care factors associated with reported activity delivery. METHODS: Cross-sectional
      telephone interview survey study of nurse managers in hospitals caring for
      patients on mechanical ventilation across Washington State in 2013. Survey
      responses were linked with hospital-level data available in the Washington State
      Department of Health Comprehensive Hospital Abstract Reporting System database.
      Chi-square testing was used to explore unadjusted associations between potential
      process of care factors and report on activity delivery. Two multivariable
      logistic regression models were developed to explore the association between
      presence of a mobility protocol and report on delivery of activity. MEASUREMENTS
      AND MAIN RESULTS: We identified 54 hospitals caring for patients on mechanical
      ventilation; 47 participated in the survey (response rate, 85.5%). Nurse managers
      from 36 (76.6%) hospitals reported use of physical activity in patients on
      mechanical ventilation, with 22 (46.8%) reporting use of high-level physical
      activity (transferring to chair, standing or ambulating) and 24 (51.1%) reporting
      use in high-severity patients (patients requiring mechanical ventilation and/or
      vasopressors). Presence of a written ICU activity protocol (odds ratio [OR],
      5.54; 95% confidence interval [CI], 1.60-19.18; P = 0.006), hospital volume (OR,
      5.33; 95% CI, 1.54-18.48; P = 0.008), and academic affiliation (OR, 4.40; 95% CI,
      1.23-15.63; P = 0.02) were associated with report of higher level activity.
      Presence of a written ICU activity protocol (OR, 6.00; 95% CI, 1.69-21.14; P =
      0.005) and academic affiliation (OR, 4.50; 95% CI, 1.21-16.46; P = 0.02) were
      associated with report of delivery of physical activity to high-severity
      patients. CONCLUSIONS: Nurse managers at three-fourths (76.6%) of eligible
      hospitals across Washington State reported use of physical activity in patients
      on mechanical ventilation. Hospital-level factors including hospital volume,
      academic affiliation, and presence of a mobility protocol were associated with
      report of higher level activity and delivery of activity to high-severity
      patients.

PMID- 25565024
TI  - The noncoding explosion.

PMID- 25565025
TI  - Roles for noncoding RNAs in cell-fate determination and regeneration.
AB  - Cellular fate is determined by transcriptional networks and epigenetic states. In
      addition to protein factors, noncoding RNAs (ncRNAs), particularly microRNAs and
      long ncRNAs, are able to remodel transcriptional circuits and reshape epigenetic
      landscapes. Here we draw upon recent findings to discuss the emerging roles of
      these ncRNAs in cellular reprogramming, transdifferentiation and organ
      regeneration. 

PMID- 25565026
TI  - Discovery and annotation of long noncoding RNAs.
AB  - Recent advances in RNA-sequencing technologies have led to the discovery of
      thousands of previously unannotated noncoding transcripts, including many long
      noncoding RNAs (lncRNAs) whose functions remain largely unknown. Here we discuss
      considerations and best practices in lncRNA identification and annotation, which
      we hope will foster functional and mechanistic exploration. 

PMID- 25565027
TI  - Using synthetic RNAs as scaffolds and regulators.
AB  - The natural versatility of RNA makes it an ideal substrate for bioengineering.
      Its structural properties and predictable base-pairing permit its use as
      molecular scaffold, and its ability to interact with nucleic acids, proteins and
      small molecules confers a regulatory potential that can be harvested to design
      RNA regulators in diverse contexts. 

PMID- 25565028
TI  - Noncoding RNAs in eukaryotic ribosome biogenesis and function.
AB  - The ribosome, central to protein synthesis in all cells, is a complex
      multicomponent assembly with rRNA at its functional core. During the process of
      ribosome biogenesis, diverse noncoding RNAs participate in controlling the
      quantity and quality of this rRNA. In this Review, I discuss the multiple roles
      assumed by noncoding RNAs during the different steps of ribosome biogenesis and
      how they contribute to the generation of ribosome heterogeneity, which affects
      normal and pathophysiological processes. 

PMID- 25565034
TI  - Groundwater Flow Field Distortion by Monitoring Wells and Passive Flux Meters.
AB  - Due to differences in hydraulic conductivity and effects of well construction
      geometry, groundwater lateral flow through a monitoring well typically differs
      from groundwater flow in the surrounding aquifer. These differences must be well
      understood in order to apply passive measuring techniques, such as passive flux
      meters (PFMs) used for the measurement of groundwater and contaminant mass
      fluxes. To understand these differences, lab flow tank experiments were performed
      to evaluate the influences of the well screen, the surrounding filter pack and
      the presence of a PFM on the natural groundwater flux through a monitoring well.
      The results were compared with analytical calculations of flow field distortion
      based on the potential theory of Drost et al. (1968). Measured well flow field
      distortion factors were found to be lower than calculated flow field distortion
      factors, while measured PFM flow field distortion factors were comparable to the
      calculated ones. However, this latter is not the case for all conditions. The
      slotted geometry of the well screen seems to make a correct analytical
      calculation challenging for conditions where flow field deviation occurs, because
      the potential theory assumes a uniform flow field. Finally, plots of the
      functional relationships of the distortion of the flow field with the hydraulic
      conductivities of the filter screen, surrounding filter pack and corresponding
      radii make it possible to design well construction to optimally function during
      PFM applications. 

PMID- 25565035
TI  - One-Step Synthesis of Single-Layer MnO2 Nanosheets with Multi-Role Sodium Dodecyl
      Sulfate for High-Performance Pseudocapacitors.
AB  - A template-free, one-step and one-phase synthesis of single-layer MnO2 nanosheets
      has been developed via a redox reaction between KMnO4 and sodium dodecyl sulfate
      (SDS). The successful formation of single-layer MnO2 nanosheets has been
      confirmed by the characteristic absorption around 374 nm and the typical
      thickness of ~0.95 nm. The slow redox reaction controlled by the gradual
      hydrolysis of SDS is found to be the key factor for the successful formation of
      single-layer nanosheets. SDS not only serves as the precursor of dodecanol to
      reduce KMnO4 , but also aids the formation of single-layer MnO2 nanosheets as a
      structure-inducing agent. The resultant single-layer MnO2 nanosheets possess
      superior specific capacitance, which can be attributed to the extended surface
      and high porosity of MnO2 nanosheets on the electrode. The MnO2 nanosheets also
      show excellent durability, retaining 91% of the starting capacitance after 10 000
      charge/discharge cycles. Moreover, the symmetric pseudocapacitor based on the
      synthesized single-layer MnO2 nanosheets exhibits a high specific capacitance,
      indicating great potential for real energy storage. Therefore, it has been
      demonstrated for the first time that a single readily available reagent, SDS, can
      play multiple roles in reducing KMnO4 to conveniently yield single-layer MnO2
      nanosheets as a high-performance pseudocapacitive material. 

PMID- 25565030
TI  - Technologies to probe functions and mechanisms of long noncoding RNAs.
AB  - Thousands of long noncoding RNAs (lncRNAs) have been discovered, but their
      functional characterization has been slowed by a limited set of research tools.
      Here we review emerging RNA-centric methods to interrogate the intrinsic
      structure of lncRNAs as well as their genomic localization and biochemical
      partners. Understanding these technologies, including their advantages and
      caveats, and developing them in the future will be essential to progress from
      description to comprehension of the myriad roles of lncRNAs. 

PMID- 25565029
TI  - From guide to target: molecular insights into eukaryotic RNA-interference
      machinery.
AB  - Since its relatively recent discovery, RNA interference (RNAi) has emerged as a
      potent, specific and ubiquitous means of gene regulation. Through a number of
      pathways that are conserved in eukaryotes from yeast to humans, small noncoding
      RNAs direct molecular machinery to silence gene expression. In this Review, we
      focus on mechanisms and structures that govern RNA silencing in higher organisms.
      In addition to highlighting recent advances, we discuss parallels and differences
      among RNAi pathways. Together, the studies reviewed herein reveal the versatility
      and programmability of RNA-induced silencing complexes and emphasize the
      importance of both upstream biogenesis and downstream silencing factors. 

PMID- 25565037
TI  - Innovative approach using interprofessional simulation to educate surgical
      residents in technical and nontechnical skills in high-risk clinical scenarios.
AB  - IMPORTANCE: The Accreditation Council for Graduate Medical Education core
      competencies stress nontechnical skills that can be difficult to evaluate and
      teach to surgical residents. During emergencies, surgeons work in
      interprofessional teams and are required to perform certain procedures. To obtain
      proficiency in these skills, residents must be trained. OBJECTIVE: To educate
      surgical residents in leadership, teamwork, effective communication, and
      infrequently performed emergency surgical procedures with the use of
      interprofessional simulations. DESIGN, SETTING, AND PARTICIPANTS: SimMan 3GS was
      used to simulate high-risk clinical scenarios (15-20 minutes), followed by
      debriefings with real-time feedback (30 minutes). A modified Oxford Non-Technical
      Skills scale (score range, 1-4) was used to assess surgical resident performance
      during the first half of the academic year (July-December 2012) and the second
      half of the academic year (January-June 2013). Anonymous online surveys were used
      to solicit participant feedback. Simulations were conducted in the operating
      room, intensive care unit, emergency department, ward, and simulation center. A
      total of 43 surgical residents (postgraduate years [PGYs] 1 and 2) participated
      in interdisciplinary clinical scenarios, with other health care professionals
      (nursing, anesthesia, critical care, medicine, respiratory therapy, and pharmacy;
      mean number of nonsurgical participants/session: 4, range 0-9). Thirty seven
      surgical residents responded to the survey. EXPOSURES: Simulation of high-risk
      clinical scenarios: postoperative pulmonary embolus, pneumothorax, myocardial
      infarction, gastrointestinal bleeding, anaphylaxis with a difficult airway, and
      pulseless electrical activity arrest. MAIN OUTCOMES AND MEASURES: Evaluation of
      resident skills: communication, leadership, teamwork, problem solving, situation
      awareness, and confidence in performing emergency procedures (eg,
      cricothyroidotomy). RESULTS: A total of 31 of 35 (89%) of the residents
      responding found the sessions useful. Additionally, 28 of 33 (85%) reported
      improved confidence doing procedures and 29 of 37 (78%) reported knowing when the
      procedure should be applied. Oxford Non-Technical Skills evaluation demonstrated
      significant improvement in PGY 2 resident performance assessed during the 2 study
      periods: communication score increased from 3 to 3.71 (P=.01), leadership score
      increased from 2.77 to 3.86 (P<.001), teamwork score increased from 3.15 to 3.86
      (P=.007), and procedural ability score increased from 2.23 to 3.43 (P=.03). There
      were no statistically significant improved scores in PGY 2 decision making or
      situation awareness. No improvements in skills were seen among PGY 1
      participants. CONCLUSIONS AND RELEVANCE: The PGY 2 residents improved their
      skills, but the PGY 1 residents did not. Participants found interprofessional
      simulations to be realistic and a valuable educational tool. Interprofessional
      simulation provides a valuable means of educating surgical residents and
      evaluating their skills in real-life clinical scenarios.

PMID- 25565036
TI  - Atrial fibrillation electrical remodelling via ablation of the epicardial neural
      networks and suprathreshold stimulation of vagosympathetic nerve.
AB  - BACKGROUND: Numerous studies have shown that the cardiac autonomic nervous system
      (CANS) is involved in the occurrence and persistence of atrial fibrillation (AF).
      The CANS is commonly considered to consist of the extrinsic and intrinsic
      autonomic nerves. The influence of exogenous and endogenous nerve stimulation
      plexus ablation on pulmonary vein sleeves and atrial myocardium provides
      important information in understanding the occurrence and persistence of AF.
      Vagosympathetic nerve stimulation and epicardial neural networks are important
      participants in atrial electrical remodelling (AER). Elucidation of the changes
      in the electrophysiological indicators of the atrial and pulmonary veins caused
      by epicardial neural network ablation and autonomic nerve stimulation may provide
      a theoretical basis for the clinical treatment of AF. MATERIAL/METHODS: A total
      of 13 beagle dogs were randomly divided into 2 groups: the control group (n=6),
      which was treated with a simple rapid atrial pacing (RAP) for 6 h, and the
      experimental group (n=7), which was treated with RAP+vagus nerve stimulation
      (VNS) for 6 h. Both groups were treated with epicardial ganglia plexus (GP)
      ablation after 6 h. We measured the monophasic action potential (MAP), various
      parts of the effective refractory period (ERP), and AF induction rate before and
      after pacing or ablation. RESULTS: With the extension of the pacing time, the
      atrial MAP and ERP of the 2 groups shortened and returned to normal after
      ablation plexus. After GP ablation, the atrial AF-induced rate did not decrease
      significantly compared with that of the pulmonary vein. CONCLUSIONS: Vagus nerve
      threshold stimulation exacerbated the deterioration of electrical remodelling,
      whereas the epicardial neural network ablation blocked or reversed the AER.

PMID- 25565038
TI  - Covalent immobilization of recombinant organophosphorus hydrolase on spores of
      Bacillus subtilis.
AB  - AIMS: Organophosphorus pesticides are widely used in agriculture. Accordingly,
      decontamination of these pesticides and their residual in environment is an
      important aim of researchers. One of the best approaches is enzymatic
      detoxification of these compounds with organophosphorus hydrolase (OPH). The
      immobilization of OPH on environmentally friendly supports is of great importance
      for developing stabilized enzymes for degradation of organophosphorus compounds.
      METHODS AND RESULTS: In this study, Bacillus subtilis spores were applied as a
      new matrix for immobilizing OPH for the first time; this enzyme was covalently
      bound to the spores by using EDC-NHS as coupling reagents and the immobilization
      was confirmed by enzymatic activity, Western blot, flow cytometry and
      fluorescence microscopic analysis. The immobilization yield was about 55% and the
      immobilized OPH hydrolysed paraoxon, an organophosphate substrate, without
      significant loss of activity was six times. The spores with immobilized OPH on
      their surface were successfully characterized using FT-IR analysis and SEM
      imaging. Thermal and pH stability was improved by immobilization of OPH on the
      spore surface. CONCLUSIONS: Owing to safety, environmentally friendly and low
      cost of spores, these spores can be employed in biosensors for monitoring and
      biodegradation of organophosphate contaminants in the environment and
      detoxification processes in bioreactors with high reusability without decrease in
      the activity. SIGNIFICANCE AND IMPACT OF THE STUDY: We believe that the spore, an
      environmentally friendly matrix, can be used for covalent immobilization of OPH
      efficiently and can be applied for detoxification of organophosphorus compounds
      under adverse environmental conditions.

PMID- 25565039
TI  - Sparse representation and dictionary learning penalized image reconstruction for
      positron emission tomography.
AB  - Accurate and robust reconstruction of the radioactivity concentration is of great
      importance in positron emission tomography (PET) imaging. Given the Poisson
      nature of photo-counting measurements, we present a reconstruction framework that
      integrates sparsity penalty on a dictionary into a maximum likelihood estimator.
      Patch-sparsity on a dictionary provides the regularization for our effort, and
      iterative procedures are used to solve the maximum likelihood function formulated
      on Poisson statistics. Specifically, in our formulation, a dictionary could be
      trained on CT images, to provide intrinsic anatomical structures for the
      reconstructed images, or adaptively learned from the noisy measurements of PET.
      Accuracy of the strategy with very promising application results from Monte-Carlo
      simulations, and real data are demonstrated. 

PMID- 25565040
TI  - Quality indicators for oesophageal and gastric cancer: a population-based study
      in Belgium, 2004-2008.
AB  - This study aimed at developing and measuring quality indicators for oesophageal
      cancer (OC) and gastric cancer (GC) and to support quality improvement for
      practitioners. Quality indicators were identified from a systematic literature
      search including clinical guidelines. The selection process involved experts
      evaluating relevance, reliability, interpretability and actionability of each
      indicator. Three national databases were linked: the cancer registry, the
      population registry and the claims database. Completeness and validity of the
      data were validated before being measured for 10,660 patients diagnosed between
      2004 and 2008. From a final set of 29 indicators, 18 were measurable using the
      available data. In 2008, less than 50% of patients were discussed at a
      multidisciplinary team meeting and less than 90% underwent a computed tomography
      scan 1 month after incidence date for cancer staging. Five-year relative survival
      was 22% for OC and 34.3% for GC. The post-operative mortality in OC patients was
      4.8% (30 days) and 9.9% (90 days), whereas it reached 5.6 and 12.0% respectively
      in GC patients. This study demonstrates the feasibility to develop a set of
      quality indicators for gastro-oesophageal cancer. A mixed picture of the quality
      of care was illustrated for some relevant care processes. Nevertheless, 5-year
      survival is higher than reported in neighbouring countries.

PMID- 25565041
TI  - Mechanisms of Carbapenem Resistance in Multidrug-Resistant Clinical Isolates of
      Pseudomonas aeruginosa from a Croatian Hospital.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen, one of the leading causes of
      nosocomial infections such as pneumonia, urinary tract infections, and
      bacteraemia. The bacterial resistance to structurally unrelated antibiotics and
      its spread within hospitals limits the efficient antimicrobial options and
      patients' outcome. Carbapenems are important agents for the therapy of infections
      due to multidrug-resistant (MDR) P. aeruginosa; hence, the development of
      carbapenem resistance severely hampers effective therapeutic options. The aim of
      this investigation was to examine mechanisms of carbapenem resistance and genomic
      diversity in carbapenem-resistant MDR strains of P. aeruginosa, which caused an
      outbreak among patients in Clinical Hospital Rijeka. Most of the isolates showed
      decreased expression of porin that is important for the entry of carbapenems
      (oprD). Overexpression of MexAB-OprM, MexCD-OprJ, and MexEF-OprN efflux systems
      was observed in many of the isolates. Production of metallo-beta-lactamases was
      not detected. Typing by pulsed-field gel electrophoresis discriminated the
      isolates into five clusters. The clonal distribution of the strains was related
      to the location of hospital departments where the isolates were collected, which
      implies that most of the infections were caused by spread of the epidemic strains
      within the hospital. 

PMID- 25565042
TI  - Determination of the centre of mass kinematics in alpine skiing using
      differential global navigation satellite systems.
AB  - In the sport of alpine skiing, knowledge about the centre of mass (CoM)
      kinematics (i.e. position, velocity and acceleration) is essential to better
      understand both performance and injury. This study proposes a global navigation
      satellite system (GNSS)-based method to measure CoM kinematics without
      restriction of capture volume and with reasonable set-up and processing
      requirements. It combines the GNSS antenna position, terrain data and the
      accelerations acting on the skier in order to approximate the CoM location,
      velocity and acceleration. The validity of the method was assessed against a
      reference system (video-based 3D kinematics) over 12 turn cycles on a giant
      slalom skiing course. The mean (+/- s) position, velocity and acceleration
      differences between the CoM obtained from the GNSS and the reference system were
      9 +/- 12 cm, 0.08 +/- 0.19 m . s(-1) and 0.22 +/- 1.28 m . s(-2), respectively.
      The velocity and acceleration differences obtained were smaller than typical
      differences between the measures of several skiers on the same course observed in
      the literature, while the position differences were slightly larger than its
      discriminative meaningful change. The proposed method can therefore be
      interpreted to be technically valid and adequate for a variety of biomechanical
      research questions in the field of alpine skiing with certain limitations
      regarding position.

PMID- 25565043
TI  - Application of polarizable ellipsoidal force field model to pnicogen bonds.
AB  - Noncovalent interactions, such as hydrogen bonds and halogen bonds, are
      frequently used in drug designing and crystal engineering. Recently, a novel
      noncovalent pnicogen bonds have been identified as an important driving force in
      crystal structures with similar bonding mechanisms as hydrogen bond and halogen
      bond. Although the pnicogen bond is highly anisotropic, the pnicogen bond angles
      range from 160 degrees  to 180 degrees  due to the complicated substituent
      effects. To understand the anisotropic characters of pnicogen bond, a
      modification of the polarizable ellipsoidal force field (PEff) model previously
      used to define halogen bonds was proposed in this work. The potential energy
      surfaces (PESs) of mono- and polysubstituted PH3 -NH3 complexes were calculated
      at CCSD(T), MP2, and density functional theory levels and were used to examine
      the modified PEff model. The results indicate that the modified PEff model can
      precisely characterize pnicogen bond. The root mean squared error of PES obtained
      with PEff model is less than 0.5 kcal/mol, compared with MP2 results. In
      addition, the modified PEff model may be applied to other noncovalent bond
      interactions, which is important to understand the role of intermolecular
      interactions in the self-assembly structures.

PMID- 25565045
TI  - Image-guided sphenoidotomy in revision functional endoscopic sinus surgery.
AB  - The application of image-guided systems to sinus surgery is gaining in
      popularity. This study tried to evaluate the efficacy of image-guided surgery
      (IGS) in the fenestration of the sphenoid sinus in patients with chronic
      rhinosinusitis (CRS) who received revision functional endoscopic sinus surgery
      (FESS). A total of 51 CRS patients who received revision FESS incorporating IGS
      between January 2010 and August 2011 by two surgeons were enrolled in this study.
      A group of 30 CRS patients who underwent revision FESS by the senior surgeon
      without incorporating IGS was chosen for comparison. The penetration rates for
      the sphenoid sinus were 91.2% when performed by the senior surgeon with IGS and
      91.3% when done by the other surgeon with IGS. The penetration rate for the
      sphenoid sinus was 68.6% for revision FESS without IGS. The fenestration rate for
      the sphenoid sinus in revision FESS without IGS was significantly lower than that
      in revision FESS with IGS (p = .004). Our results showed that IGS was a
      beneficial procedure for opening the sphenoid sinus in the revision cases. 

PMID- 25565046
TI  - Treatment of chronic frontal sinusitis with difficult anatomy: A hybrid balloon
      technique in four cases.
AB  - The presence of frontal cells poses unique challenges when using endoscopic
      approaches. This study describes the use of a balloon dilation system as an aid
      for functional endoscopic sinus surgery (FESS) to access the frontal sinus in
      cases that would traditionally require open approaches. We present a case series
      of four patients with chronic rhinosinusitis refractive to medical management who
      underwent FESS with the aid of a balloon dilation system at a tertiary referral
      center. All patients had variant forms of frontal sinus anatomy. Surgical
      techniques will be described and use of the balloon system will be reviewed. All
      patients (aged 13-68 years) successfully underwent fontal sinusotomies with the
      assistance of a balloon dilation system, which was used in a variety of ways: to
      dilate the narrow infundibulum of a high intersinus septal cell, to remove an
      anteriorly located type III frontal sinus cell, to expand the natural frontal
      ostium in the presence of excessive agger nasi pneumatization, and to remove a
      type IV frontal sinus cell. All patients were spared an osteoplastic flap or
      trephination, and there were no intraoperative complications. No postoperative
      bleeding, infection, or cerebral spinal fluid leaks were reported. Balloon
      dilation in combination with standard frontal sinus dissection techniques may be
      beneficial for a select group of patients with complex frontal anatomy. In this
      series of patients, the balloon dilation system was used as a tool during FESS
      and eliminated the need for open approaches. 

PMID- 25565047
TI  - Effect of oxygen tension on tissue-engineered human nasal septal chondrocytes.
AB  - Tissue-engineered nasal septal cartilage may provide a source of autologous
      tissue for repair of craniofacial defects. Although advances have been made in
      manipulating the chondrocyte culture environment for production of neocartilage,
      consensus on the best oxygen tension for in vitro growth of tissue-engineered
      cartilage has not been reached. The objective of this study was to determine
      whether in vitro oxygen tension influences chondrocyte expansion and
      redifferentiation. Proliferation of chondrocytes from 12 patients expanded in
      monolayer under hypoxic (5% or 10%) or normoxic (21%) oxygen tension was compared
      over 14 days of culture. The highest performing oxygen level was used for further
      expansion of the monolayer cultures. At confluency, chondrocytes were
      redifferentiated by encapsulation in alginate beads and cultured for 14 days
      under hypoxic (5 or 10%) or normoxic (21%) oxygen tension. Biochemical and
      histological properties were evaluated. Chondrocyte proliferation in monolayer
      and redifferentiation in alginate beads were supported by all oxygen tensions
      tested. Chondrocytes in monolayer culture had increased proliferation at normoxic
      oxygen tension (p = 0.06), as well as greater accumulation of glycosaminoglycan
      (GAG) during chondrocyte redifferentiation (p < 0.05). Chondrocytes released from
      beads cultured under all three oxygen levels showed robust accumulation of GAG
      and type II collagen with a lower degree of type I collagen immunoreactivity.
      Finally, formation of chondrocyte clusters was associated with decreasing oxygen
      tension (p < 0.05). Expansion of human septal chondrocytes in monolayer culture
      was greatest at normoxic oxygen tension. Both normoxic and hypoxic culture of
      human septal chondrocytes embedded in alginate beads supported robust
      extracellular matrix deposition. However, GAG accumulation was significantly
      enhanced under normoxic culture conditions. Chondrocyte cluster formation was
      associated with hypoxic oxygen tension. 

PMID- 25565048
TI  - Levamisole-adulterated cocaine induced skin necrosis of nose, ears, and
      extremities: Case report.
AB  - Levamisole is an immunomodulatory and antihelminthic drug, previously removed
      from the United States market, and now estimated to be present in the vast
      majority of cocaine distributed in the United States. Levamisole-adulterated
      cocaine (LAC) exposure can result in neutropenia, thrombocytopenia, and
      vasculitis with a predilection for subsites of the face. The objective of this
      review is to increase awareness among otolaryngologists of the manifestations of
      LAC exposure. We present the case of a 33-year-old woman with a history of
      cocaine use, consulted for purpuric, necrotic lesions of the nose, cheeks, and
      ears, with accompanying leukopenia, thrombocytopenia, and positive antineutrophil
      cytoplasmic antibodies (ANCA). The effects of levamisole are immune mediated,
      with antibodies directed against neutrophils causing neutropenia, and vasculitis
      caused by antibody deposition or secondary to induction of antiphospholipid
      antibodies causing thrombosis. LAC exposure can be differentiated from other
      similar appearing pathologies by evaluating serology for specific ANCA. The most
      important treatment is cessation of cocaine use, which most often results in
      complete resolution of symptoms. Awareness of the presentation, complications,
      and treatment of LAC exposure may be especially important for otolaryngologists,
      who may be one of the firsts to evaluate an affected patient. 

PMID- 25565049
TI  - Tonsil volume and allergic rhinitis in children.
AB  - Tonsil hypertrophy (TH) is very common in children. Previously, it has been
      reported that an inverse relationship exists between adenoid hypertrophy (AH) and
      allergic rhinitis (AR). This study aimed to investigate the possible relationship
      between tonsil volume and AR diagnosis in a group of children complaining of
      upper airways obstruction. Globally, 171 children (91 boys; mean age, 6.6 years)
      were studied. Clinical visit, nasal endoscopy, and skin-prick test were performed
      in all patients. TH and anterior nasal obstruction were graded using the
      Friedman's classifications. Adenoid volume was graded using the Parikh's
      classification. Fifty-eight children (33.9%) had relevant TH (grades 3-4); 77
      children (44.94%) had AR. There was a strong correlation (gamma = 0.564; p <
      0.001) between TH and AH. Tonsil volume was inversely associated with AR
      diagnosis (odds ratio [OR], 0.314). Risk factors for TH were intense mucosal
      inflammation (pale mucous membranes) and AH (OR, 3.54 and 2.856, respectively).
      This study shows that large tonsils are negatively associated with allergy,
      whereas intense inflammation is a risk factor for TH; AH may be frequently
      associated with TH. 

PMID- 25565050
TI  - Characterization of aeroallergen sensitivities in children with allergic rhinitis
      and chronic rhinosinusitis.
AB  - Allergic rhinitis is a common comorbid condition in pediatric chronic
      rhinosinusitis (CRS). Testing for aeroallergen sensitization should therefore be
      considered in the evaluation of children with CRS. At present the aeroallergen
      sensitivity profile of children with CRS remains uncharacterized. In this study,
      we retrospectively identify a consecutive series of children with CRS and
      allergic rhinitis who have undergone joint otolaryngology and allergy evaluation
      at a single tertiary care center. We describe the aeroallergen sensitivity
      profiles (based upon formal skin testing) of these children, stratifying them
      according to co-morbidity status: 1) CRS with cystic fibrosis (CF), 2) CRS with
      immune deficiency and 3) uncomplicated CRS (without co-morbid CF, immune
      deficiency or primary ciliary dyskinesia). We identify 208 children (average age
      9.3 years, standard deviation 4.8 years) with CRS and allergic rhinitis meeting
      inclusion criteria, 140 with uncomplicated CRS, 64 with co-morbid immune
      deficiency and 4 with co-morbid CF. The prevalence of indoor aeroallergen
      sensitivities (62.9-100.0%) was more common than that of outdoor aeroallergen
      sensitivities (43.8-50.0%) in all three cohorts of children. In all three
      cohorts, the most common indoor aeroallergen sensitivity was to dust mites (50.0
      75.0%) and the most common outdoor aeroallergen sensitivity was to tree pollens
      (43.8-50.0%). The aeroallergen sensitivity profile of children with CRS and
      allergic rhinitis appears to be similar to that of the general pediatric
      population with allergic rhinitis, and parallels the aeroallergen sensitivities
      previously described for adults with CRS and allergic rhinitis. Knowledge of the
      aeroallergen sensitivities in children with CRS and allergic rhinitis will
      enhance both diagnostic and treatment strategies. 

PMID- 25565051
TI  - CD8(+) T cells implicated in the pathogenesis of allergic fungal rhinosinusitis.
AB  - Fungi in paranasal sinuses are characteristic and considered a major pathogenic
      factor in a subset of chronic rhinosinusitis (CRS) patients, known as allergic
      fungal rhinosinusitis (AFRS). CD8(+) T cells are enriched in AFRS sinuses but
      their role in fungal-specific responses is unknown. Alternaria alternata- and
      Aspergillus fumigatus-specific T lymphocyte responses were investigated in 6 AFRS
      patients, 10 eosinophilic mucus CRS (EMCRS) patients, 10 CRS with nasal polyps
      (CRSwNPs) patients, 6 allergic rhinitis with fungal allergy (ARFA) patients, and
      five controls. Fungal-specific proliferation of human peripheral blood
      mononuclear cells (PBMCs) was studied prospectively. Proliferating cells were
      examined for CD3, CD4, CD8, and CD25 expression. Relevant clinical
      characteristics, fungal allergy, detection of fungi in sinuses, and CD4(+) and
      CD8(+) composition of sinus T cells were also examined. CD4(+) T-cell division to
      fungi occurred in all samples, regardless of fungal allergy or CRS. Fungal
      specific CD8(+) T-cell division occurred in all ARFA and control samples and the
      majority of CRSwNP patients; however, CD8(+) T cells failed to proliferate in
      AFRS and EMCRS patients. The CD8(+) T cells from AFRS patients also did not up
      regulate the activation marker, CD25, with fungal antigen exposure. Presence of
      A. alternata- and A. fumigatus-specific CD4(+) and CD8(+) T-cell proliferation in
      healthy individuals, ARFA, and CRSwNP patients suggests that both T-cell subsets
      may be important in immune responses to these fungi. In AFRS and EMCRS patients,
      only fungal-specific CD4(+) T-cell proliferation occurred; hence, a lack of
      CD8(+) T-cell proliferation and activation in the presence of sinus eosinophilic
      mucus in these patients, regardless of fungal allergy, is a novel finding. This
      raises the question whether a dysfunctional CD8(+) T-cell response predisposes to
      ineffective clearance and accumulation of fungi in the sinuses of susceptible
      patients. 

PMID- 25565052
TI  - Fractional exhaled nitric oxide (FeNo) in different asthma phenotypes.
AB  - Fractioned exhaled nitric oxide (FeNO) is a noninvasive marker of inflammation in
      asthmatic patients. FeNO can be used to monitor airway inflammation, but
      individual responses make tailored interventions based on FeNO difficult. The
      correlation between the asthma control test (ACT), FEV1, and FeNO was evaluated
      in this study to ascertain the correct usage of FeNO with different asthma
      phenotypes regarding their control, allergy, comorbidity, obesity, age, smoking
      status, and severity. ACT, pulmonary function, and FeNO in 416 asthmatic patients
      on combined therapy were retrospective evaluated. Correlations between these
      parameters and the FeNO levels in different asthma phenotypes were calculated. In
      the study population, FeNO was 31.8 +/- 28.5 parts per billion (ppb), FEV1 was
      83.4 +/- 19% and ACT was 19 +/- 5.2. ACT scores were negatively correlated with
      FeNO (r = -0.31; p = 0.002). FeNO was different in patients with positive and
      negative skin-prick test (p < 0.05), with and without allergic rhinitis (p <
      0.01), and with and without allergic conjunctivitis (p < 0.01). Significantly
      higher FeNO levels were found with logistic regression analysis only in patients
      with a history of emergency room visits (ERVs) (p = 0.024). The rate of the ERV
      of the patients with an ACT score more than or equal to 20 and with a FeNO value
      of more than 35 ppb was 22.9%, but with a FeNO value of less than 35 ppb was 6.5%
      (p = 0.004). Allergy and allergic comorbidities may lead to an increase in FeNO
      levels. Patients with a history of ERV have markedly higher FeNO levels, although
      they have an ACT score more than or equal to 20. 

PMID- 25565044
TI  - Organic carbamates in drug design and medicinal chemistry.
AB  - The carbamate group is a key structural motif in many approved drugs and
      prodrugs. There is an increasing use of carbamates in medicinal chemistry and
      many derivatives are specifically designed to make drug-target interactions
      through their carbamate moiety. In this Perspective, we present properties and
      stabilities of carbamates, reagents and chemical methodologies for the synthesis
      of carbamates, and recent applications of carbamates in drug design and medicinal
      chemistry. 

PMID- 25565054
TI  - Anterior ethmoidal artery emerging anterior to bulla ethmoidalis: An abnormal
      anatomical variation in Waardenburg's syndrome.
AB  - In endoscopic sinus surgery, the anterior ethmoidal artery (AEA) is usually
      identified as it traverses obliquely across the fovea ethmoidalis, posterior to
      the bulla ethmoidalis and anterior to or within the ground lamella's attachment
      to the skull base. Injury to the AEA may result in hemorrhage, retraction of the
      AEA into the orbit, and a retrobulbar hematoma. The resulting increase in
      intraorbital pressure may threaten vision. Waardenburg's syndrome (WS) is a rare
      congenital, autosomal dominantly inherited disorder, distinguished by
      characteristic facial features, pigmentation abnormalities, and profound,
      congenital, sensorineural hearing loss. We present a case of AEAs located
      anterior to the bulla ethmoidalis in a 36-year-old male with WS and chronic
      rhinosinusitis. The anatomic abnormality was not obvious on a preoperative
      computed tomography scan and was discovered intraoperatively when the left AEA
      was injured, resulting in a retrobulbar hematoma. The hematoma was immediately
      identified and decompressed endoscopically without lasting complications. The AEA
      on the right was identified intraoperatively and preserved. The characteristic
      craniofacial features in WS were probably associated with the abnormal vascular
      anatomy. Endoscopic sinus surgeons should be aware of these potential anatomic
      anomalies in patients with abnormal craniofacial development. 

PMID- 25565053
TI  - Sinonasal phosphaturic mesenchymal tumor: Case report and systematic review.
AB  - We report a case of sinonasal phosphaturic mesenchymal tumor (PMT) and conduct a
      systematic review of the literature to highlight a unique paraneoplastic syndrome
      associated with PMT. We used English language publications from Medline and
      Cochrane databases (1970-2013) as data sources. A systematic review of the
      literature was conducted. All reported cases of head and neck PMTs were included.
      The presence or absence of the associated paraneoplastic syndrome was noted. We
      found 33 cases of PMT in the head and neck reported in the literature, 17 of
      which occurred in the sinonasal area. Approximately 5% of all PMTs are located in
      the head and neck. Just greater than half are concentrated in the sinonasal area,
      and the remaining involve various bony and soft tissue structures of the head and
      neck. PMT is sometimes associated with a paraneoplastic syndrome of tumor-induced
      (oncogenic) osteomalacia (TIO) causing bone pain, muscle weakness, and pathologic
      fractures. We present the 18th reported case of sinonasal PMT. A smooth mucosa
      covered midline intraseptal mass filling the posterior nasal cavity with
      destruction and erosion of the skull base was found in an adult male. The patient
      underwent successful endoscopic resection with wide negative margins and is
      without recurrence at 24-month follow-up. PMT is a benign, locally aggressive
      tumor with rare malignant transformation. Knowledge of the bony invasion and
      destruction caused by this tumor is essential in planning surgical resection with
      wide negative margins. Familiarity with the associated TIO is essential to
      investigate for and manage any associated bony morbidity. 

PMID- 25565055
TI  - Novel treatment of allergic fungal sinusitis using omalizumab.
AB  - A case report of recalcitrant allergic fungal sinusitis (AFS) refractory to
      systemic corticosteroids and multiple functional endoscopic sinus surgeries
      (FESSs) treated with anti-IgE antibody omalizumab is reported. AFS is often
      classified with chronic rhinosinusitis (CRS). Although similar symptoms are among
      the two diseases, AFS has a unique pathophysiology. Patients with AFS demonstrate
      type 1 hypersensitivity to fungal allergens, increased total serum IgE, increased
      CD8(+) T-cell prevalence, and IL-4 and IL-5 response. Omalizumab should be
      considered in the treatment of AFS. 

PMID- 25565057
TI  - Treatment of giant/large internal carotid aneurysms: parent artery occlusion or
      stent-assisted coiling.
AB  - PURPOSE: Treatment of giant/large internal carotid aneurysm is a challenge for
      neurologists. Previously, parent artery occlusion was the classic therapy; now
      the stent-assisted coil embolization has become available in recent years, but
      the optimal therapy is under debate. The goal of the present study was to compare
      two endovascular treatment modalities in terms of safety, efficacy and short-term
      outcomes. METHODS: All the patients were divided into two groups: Group A:
      patients who underwent parent artery occlusion, and Group B: patients who
      underwent stent-assisted coil embolization. Follow-up outcomes were evaluated
      using the modified Rankin Scale (mRS). RESULTS: After 12 months of follow-up, the
      favorable outcome (mRS: 0-2) had no statistical significance in both groups (p =
      1.00). Patients in group A had greater ischemia compared with patients in group
      B, but the difference did not reach statistical significance (p = 0.421). In
      group B, patients had a higher rate of partial occlusion (p = 0.255) and
      recurrence (10% vs. 0%; p = 0.586). CONCLUSIONS: Stent-assisted coiling may not
      be superior to parent artery occlusion in selected patients after short-term
      follow-up. Parent artery occlusion is a simple, safe and effective treatment for
      large/giant internal carotid aneurysms.

PMID- 25565058
TI  - Macroscopic and microscopic study of 1-ethyl-3-methyl-imidazolium acetate-DMSO
      mixtures.
AB  - Macroscopic (steady-state viscosity, density) and microscopic (NMR chemical
      shifts, (1)H NMR relaxation times, and diffusion) properties of the 1-ethyl-3
      methylimidazolium acetate ([EMIM][OAc])-dimethyl sulfoxide (DMSO) mixture were
      studied in detail as a function of DMSO molar fraction at various temperatures.
      Temperature dependencies were used to calculate the activation energies. NMR
      results indicate that at low molar fraction of DMSO (<0.4), it weakly associates
      with the cation and in doing so disrupts the strong ion-ion association that
      exists in the pure ionic liquid. Stokes-Einstein equation, which linearly
      correlates the diffusion coefficient of a spherical molecule and macroscopic
      viscosity, was shown to work well for the [EMIM][OAc]-DMSO mixture. The influence
      of DMSO on the "anomalous" diffusion in [EMIM][OAc] ("quick" cation vs "slow"
      anion) was investigated; it was demonstrated that DMSO makes the cation diffusion
      slower. All parameters studied showed relatively small deviations from the ideal
      mixing rule behavior (from 20% to 50% difference between experimental and
      theoretically predicted results), confirming weak interactions between the
      components. 

PMID- 25565056
TI  - Otolithic information is required for homing in the mouse.
AB  - Navigation and the underlying brain signals are influenced by various allothetic
      and idiothetic cues, depending on environmental conditions and task demands.
      Visual landmarks typically control navigation in familiar environments but, in
      the absence of landmarks, self-movement cues are able to guide navigation
      relatively accurately. These self-movement cues include signals from the
      vestibular system, and may originate in the semicircular canals or otolith
      organs. Here, we tested the otolithic contribution to navigation on a food
      hoarding task in darkness and in light. The dark test prevented the use of visual
      cues and thus favored the use of self-movement information, whereas the light
      test allowed the use of both visual and non-visual cues. In darkness, tilted mice
      made shorter-duration stops during the outward journey, and made more circuitous
      homeward journeys than control mice; heading error, trip duration, and peak error
      were greater for tilted mice than for controls. In light, tilted mice also showed
      more circuitous homeward trips, but appeared to correct for errors during the
      journey; heading error, trip duration, and peak error were similar between
      groups. These results suggest that signals from the otolith organs are necessary
      for accurate homing performance in mice, with the greatest contribution in non
      visual environments.

PMID- 25565059
TI  - Anticipating action effects with different attention foci is reflected in brain
      activation.
AB  - Anticipation is informed by experience. Having focused on action effects in the
      past will lead to differences when the focus is now on the effector. Boules-type
      throwing movements were presented as point-light displays of shoulder and arm
      markers. Activation in motor-related areas measured with functional magnetic
      resonance imaging was compared between two tasks: Task A anticipating action
      effects and Task B judging the velocity of the hand marker. One group of
      participants performed a session of Task A followed by a session of Task B; the
      other group started with Task B followed by Task A. The group starting with Task
      A exhibited higher brain activation during Task A bilaterally in intraparietal
      areas and in right hemispheric frontal and premotor areas. These areas are known
      to be involved in effect estimation and action simulation. The second group
      showed higher activation during Task B in premotor cortex and human intraparietal
      area 3 of the right hemisphere. The results suggest that the instruction to focus
      on anticipating action effects facilitates the recruitment of core components of
      the simulation network during anticipation and when effect anticipation is not
      the primary intention.

PMID- 25565060
TI  - Identification of a new HLA-DRB1*04 allele, DRB1*04:10:03.
AB  - The new allele, DRB1*04:10:03, showed one nucleotide difference with
      DRB1*04:10:01 (705C>T). 

PMID- 25565061
TI  - Focus on Ebola virus research.

PMID- 25565062
TI  - Paper-based thin-layer coulometric sensor for halide determination.
AB  - We report on a paper-based analytical device (PAD) for the exhaustive, and
      therefore absolute, determination of halides in a range of diverse water samples
      and food supplements. A mixture of chloride, bromide, and iodide ions is assessed
      in a wide range of concentrations, specifically, from 10(-4.8) to 0.1 M for
      bromide and iodide and from 10(-4.5) to 0.6 M for chloride, with a limit of
      detection of 10(-5) M. As a result of a careful optimization of the
      electrochemical cell, a thin layer made of cellulose paper (75-MUm thickness), a
      cation-exchange Donnan exclusion membrane (FKL), and a silver-foil working
      electrode were selected as optimum materials. Cyclic voltammetry (from 0 to 0.8
      V) was chosen as the interrogation technique to impose the exhaustive oxidative
      plating and re-reduction of halides on the silver element, accompanied by outward
      and inward counterion fluxes. The scan rate plays an important role in the
      ability of the technique to resolve mixtures of ions. Moderate scan rates (10 mV
      s(-1)) provide a suitable compromise between sensitivity, limit of detection, and
      resolution. This paper-based microfluidic device is extremely simple in terms of
      manipulation, cost, and contamination risk. Paper is an excellent basis for the
      establishment of a confined thin aqueous layer, the construction of disposable
      halide sensors, and portability for measuring outside the controlled laboratory
      environment. A discussion of the relevant analytical characteristics is presented
      herein, followed by a demonstration of halide assessment in water samples (sea,
      tap, river, and mineral waters) and food supplements enriched with iodide and
      chloride as early examples. 

PMID- 25565065
TI  - Design of the North Carolina Prostate Cancer Comparative Effectiveness and
      Survivorship Study (NC ProCESS).
AB  - The North Carolina Prostate Cancer Comparative Effectiveness & Survivorship Study
      (NC ProCESS) was designed in collaboration with stakeholders to compare the
      effectiveness of different treatment options for localized prostate cancer. Using
      the Rapid Case Ascertainment system of the North Carolina Central Cancer
      Registry, 1,419 patients (57% of eligible) with newly-diagnosed localized
      prostate cancer were enrolled from January 2011 to June 2013, on average 5 weeks
      after diagnosis. All participants were enrolled prior to treatment and this
      population-based cohort is sociodemographically diverse. Prospective follow-up
      continues to collect data on treatments received, disease control, survival and
      patient-reported outcomes. This study highlights several important considerations
      regarding stakeholder involvement, study design and generalizability regarding
      comparative effectiveness research in prostate cancer. 

PMID- 25565063
TI  - Trends in imaging after diagnosis of thyroid cancer.
AB  - BACKGROUND: The largest growth noted among differentiated thyroid cancer (DTC)
      diagnosis is in low-risk cancers. Trends in imaging after the diagnosis of DTC
      are understudied. Hypothesizing a reduction in imaging use due to rising low-risk
      disease, the authors evaluated postdiagnosis imaging patterns over time and
      patient characteristics that are associated with the likelihood of imaging.
      METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database,
      the authors identified patients diagnosed with localized, regional, or distant
      DTC between 1991 and 2009. Medicare claims were reviewed for use of neck
      ultrasound, iodine-131 (I-131) scan, or positron emission tomography (PET) scan
      within 3 years after diagnosis. Trends in imaging use were evaluated using
      regression analyses. Multivariable logistic regression was used to estimate the
      likelihood of imaging based on patient characteristics. RESULTS: A total of
      23,669 patients were included. Compared with patients diagnosed between 1991 and
      2000, those diagnosed between 2001 and 2009 were more likely to have localized
      disease (P<.001) and tumors measuring <1 cm (P<.001). Use of neck ultrasound and
      I-131 scans increased in patients with localized disease (P <=.001 and P = .003,
      respectively), regional disease (P<.001 and P<.001, respectively), and distant
      metastasis (P = .001 and P = .015, respectively). Patients diagnosed after 2000
      were more likely to undergo neck ultrasound (odds ratio, 2.15; 95% confidence
      interval, 2.02-2.28) and I-131 scan (odds ratio, 1.44; 95% confidence interval,
      1.35-1.54). Compared with 1996 through 2004, PET scan use from 2005 to 2009
      increased 32.4-fold (P<=.001) in patients with localized disease, 13.1-fold
      (P<.001) in patients with regional disease, and 33.4-fold (P<.001) in patients
      with distant DTC. CONCLUSIONS: Despite an increase in the diagnosis of low-risk
      disease, the use of postdiagnosis imaging increased among patients with all
      stages of disease. The largest growth observed was in the use of PET after 2004.

PMID- 25565066
TI  - Patient and clinician views on comparative effectiveness research and engagement
      in research.
AB  - AIMS: Describe and compare patient and primary care clinician attitudes about
      comparative effectiveness research (CER) and inclusion of patients and clinicians
      as partners in clinical research. MATERIALS & METHODS: Online survey of patients
      (n = 900) and primary care clinicians (n = 750) from opt-in survey panels.
      RESULTS: Nearly half (45%) of clinicians were not familiar with CER, but after
      reviewing a definition of CER, most (76%) agreed that it can improve patient
      care. Patients and clinicians indicated interest in engagement as research
      partners (66% and 55%, respectively). Lack of time was the most commonly endorsed
      barrier. CONCLUSION: Attitudes toward CER and engagement in clinical research
      were generally favorable. Identified facilitators and barriers point to
      strategies for enhancing patient and clinician engagement in research.

PMID- 25565067
TI  - Revisiting the washout period in the incident user study design: why 6-12 months
      may not be sufficient.
AB  - AIMS: The purpose of this study was to describe how washout period duration
      affects the size and accuracy of retrospective incident user cohorts. MATERIALS &
      METHODS: MarketScan commercial claims data from 2007 to 2010 were used and
      included adults with an antihyperlipidemic, antidiabetic or antidepressant claim
      in 2010. Incident user cohorts using 3-, 6-, 12-, 24- and 36-month washouts were
      created and changes in sample size and incident user misclassification were
      described. RESULTS & CONCLUSION: The 6- and 12-month washouts excluded 75 and 85%
      of the samples, respectively. Half of subjects in the 6-month washout cohorts
      were actually prevalent users, and the 12-month washout period resulted in 30%
      misclassified. Using common washout periods of 6-12 months may insufficiently
      address prevalent user bias in large commercial claims databases.

PMID- 25565068
TI  - Comparative effectiveness of colony-stimulating factors in febrile neutropenia
      prophylaxis: how results are affected by research design.
AB  - AIMS: To examine the impact of research design on results in two published
      comparative effectiveness studies. METHODS: Guidelines for comparative
      effectiveness research have recommended incorporating disease process in study
      design. Based on the recommendations, we develop a checklist of considerations
      and apply the checklist in review of two published studies on comparative
      effectiveness of colony-stimulating factors. Both studies used similar
      administrative claims data, but different methods, which resulted in
      directionally different estimates. RESULTS: Major design differences between the
      two studies include: whether the timing of intervention in disease process was
      identified and whether study cohort and outcome assessment period were defined
      based on this temporal relationship. CONCLUSION: Disease process and timing of
      intervention should be incorporated into the design of comparative effectiveness
      studies.

PMID- 25565069
TI  - Comparative effectiveness research and big data: balancing potential with legal
      and ethical considerations.
AB  - Big data holds big potential for comparative effectiveness research. The ability
      to quickly synthesize and use vast amounts of health data to compare medical
      interventions across settings of care, patient populations, payers and time will
      greatly inform efforts to improve quality, reduce costs and deliver more patient
      centered care. However, the use of big data raises significant legal and ethical
      issues that may present barriers or limitations to the full potential of big
      data. This paper addresses the scope of some of these legal and ethical issues
      and how they may be managed effectively to fully realize the potential of big
      data. 

PMID- 25565070
TI  - A national data infrastructure for patient-centered outcomes research.
AB  - Concerted efforts are underway to improve healthcare decision-making through
      patient-centered outcomes research. These efforts are supported by the Patient
      Centered Outcomes Research Trust Fund, which was established within the Patient
      Protection and Affordable Care Act. This article focuses on describing national
      data infrastructure efforts that support patient-centered outcomes research. A
      national data infrastructure has the potential to decrease research costs and
      improve research throughput. We describe early and current efforts that
      demonstrated this potential, how the national effort is utilizing the lessons
      learned from these predecessor efforts and remaining challenges. 

PMID- 25565072
TI  - Computational study on the mechanisms and rate constants of the Cl-initiated
      oxidation of methyl vinyl ether in the atmosphere.
AB  - The Cl-initiated oxidation reactions of methyl vinyl ether (MVE) are analyzed by
      using the high-level composite method CBS-QB3. Detailed chemistry for the
      reactions of MVE with chlorine atoms is proposed according to the calculated
      thermodynamic data. The primary eight channels, including two Cl-addition
      reactions and six H-abstraction reactions, are discussed. In accordance with the
      further investigation of the two dominant additional routes, formyl chloride and
      formaldehyde are the major products. Over the temperature range of 200-400 K and
      the pressure range of 100-2000 Torr, the rate constants of primary reactions are
      calculated by employing the MESMER program. H-abstraction channels are negligible
      according to the value of rate constants. During the studied temperature range,
      the Arrhenius equation is obtained as ktot = 5.64 * 10(-11) exp(215.1/T). The
      total rate coefficient is ktot = 1.25 * 10(-10) cm(3) molecule(-1) s(-1) at 298 K
      and 760 Torr. Finally, the atmospheric lifetime of MVE with respect to Cl is
      estimated to be 2.23 h. 

PMID- 25565071
TI  - An investigation into the relationship between age and physiological function in
      highly active older adults.
AB  - KEY POINTS: The relationship between age and physiological function remains
      poorly defined and there are no physiological markers that can be used to
      reliably predict the age of an individual. This could be due to a variety of
      confounding genetic and lifestyle factors, and in particular to ill-defined and
      low levels of physical activity. This study assessed the relationship between age
      and a diverse range of physiological functions in a cohort of highly active older
      individuals (cyclists) aged 55-79 years in whom the effects of lifestyle factors
      would be ameliorated. Significant associations between age and function were
      observed for many functions. VO2max was most closely associated with age, but
      even here the variance in age for any given level was high, precluding the clear
      identification of the age of any individual. The data suggest that the
      relationship between human ageing and physiological function is highly
      individualistic and modified by inactivity. ABSTRACT: Despite extensive research,
      the relationship between age and physiological function remains poorly
      characterised and there are currently no reliable markers of human ageing. This
      is probably due to a number of confounding factors, particularly in studies of a
      cross-sectional nature. These include inter-subject genetic variation, as well as
      inter-generational differences in nutrition, healthcare and insufficient levels
      of physical activity as well as other environmental factors. We have studied a
      cohort of highly and homogeneously active older male (n = 84) and female (n = 41)
      cyclists aged 55-79 years who it is proposed represent a model for the study of
      human ageing free from the majority of confounding factors, especially
      inactivity. The aim of the study was to identify physiological markers of ageing
      by assessing the relationship between function and age across a wide range of
      indices. Each participant underwent a detailed physiological profiling which
      included measures of cardiovascular, respiratory, neuromuscular, metabolic,
      endocrine and cognitive functions, bone strength, and health and well-being.
      Significant associations between age and function were observed for many
      functions. The maximal rate of oxygen consumption (VO2max) showed the closest
      association with age (r = -0.443 to -0.664; P < 0.001), but even here the
      variance in age for any given level was high, precluding the clear identification
      of the age of any individual. The results of this cross-sectional study suggest
      that even when many confounding variables are removed the relationship between
      function and healthy ageing is complex and likely to be highly individualistic
      and that physical activity levels must be taken into account in ageing studies.

PMID- 25565074
TI  - Direct measurement of local dissolved oxygen concentration spatial profiles in a
      cell culture environment.
AB  - Controlling local dissolved oxygen concentration (DO) in media is critical for
      cell or tissue cultures. Various biomaterials and culture methods have been
      developed to modulate DO. Direct measurement of local DO in cultures has not been
      validated as a method to test DO modulation. In the present study we developed a
      DO measurement system equipped with a Clark-type oxygen microelectrode
      manipulated with 1 MUm precision in three-dimensional space to explore potential
      applications for tissue engineering. By determining the microelectrode tip
      position precisely against the bottom plane of culture dishes with rat or human
      cardiac cells in static monolayer culture, we successfully obtained spatial
      distributions of DO in the medium. Theoretical quantitative predictions fit the
      obtained data well. Based on analyses of the variance between samples, we found
      the data reflected "local" oxygen consumption in the vicinity of the
      microelectrode and the detection of temporal changes in oxygen consumption rates
      of cultured cells was limited by the diffusion rate of oxygen in the medium. This
      oxygen measuring system monitors local oxygen consumption and production with
      high spatial resolution, and can potentially be used with recently developed
      oxygen modulating biomaterials to design microenvironments and non-invasively
      monitor local DO dynamics during culture.

PMID- 25565075
TI  - New tools for the nutritional assessment and management of critical care
      patients.

PMID- 25565073
TI  - Interphotoreceptor retinoid-binding protein protects retinoids from
      photodegradation.
AB  - Retinol degrades rapidly in light into a variety of photoproducts. It is
      remarkable that visual cycle retinoids can evade photodegradation as they are
      exchanged between the photoreceptors, retinal pigment epithelium and Muller glia.
      Within the interphotoreceptor matrix, all-trans retinol, 11-cis retinol and
      retinal are bound by interphotoreceptor retinoid-binding protein (IRBP). Apart
      from its role in retinoid trafficking and targeting, could IRBP have a
      photoprotective function? HPLC was used to evaluate the ability of IRBP to
      protect all-trans and 11-cis retinols from photodegradation when exposed to
      incandescent light (0 to 8842 MUW cm(-2)); time periods of 0-60 min, and bIRBP:
      retinol molar ratios of 1:1 to 1:5. bIRBP afforded a significant prevention of
      both all-trans and 11-cis retinol to rapid photodegradation. The effect was
      significant over the entire light intensity range tested, and extended to the
      bIRBP: retinol ratio 1:5. In view of the continual exposure of the retina to
      light, and the high oxidative stress in the outer retina, our results suggest
      IRBP may have an important protective role in the visual cycle by reducing
      photodegradation of all-trans and 11-cis retinols. This role of IRBP is
      particularly relevant in the high flux conditions of the cone visual cycle.

PMID- 25565076
TI  - High-dose dexmedetomidine for noninvasive pediatric procedural sedation and
      discharge readiness.
AB  - BACKGROUND: The University of North Carolina's (UNC) Pediatric Sedation Service
      adopted a noninvasive procedural sedation protocol that uses dexmedetomidine in
      children based on review of literature that reported fast recovery times and low
      morbidity. This study aimed to compare dexmedetomidine discharge readiness times
      observed at UNC with those previously published with a hypothesis that the
      discharge times at UNC are longer than those previously published. A secondary
      aim was to evaluate the safety profile of the protocol. METHODS: Pediatric
      outpatients (6 months-18 years) who received dexmedetomidine per protocol for a
      noninvasive procedure or study from January 2011 through April 2012 were included
      in this retrospective chart review. A total of 615 patient encounters were
      evaluated. Patients received bolus doses of 2 MUg.kg(-1) over 10 min for up to
      three doses followed by a 1 MUg.kg(-1) .h(-1) infusion (group 1) or a 1.5 MUg.kg(
      1) .h(-1) infusion (group 2). Primary outcomes included time to sedation, time to
      arousal, and time to discharge. RESULTS: No significant differences between the
      dosing groups were noted. Time to discharge was significantly shorter for group 1
      (79 min) than for group 2 (101 min). The range of discharge times at UNC was 78.7
      100.9 min compared to previous studies that report recovery times of 24.8-35.2
      min. CONCLUSION: Dexmedetomidine arousal and discharge times observed at UNC were
      longer than anticipated when compared to literature. The safety profile of the
      drug was comparable to prior studies.

PMID- 25565077
TI  - The effects of parental illness and other ill family members on youth caregiving
      experiences.
AB  - Informed by a model of family role redistribution derived from the family ecology
      framework, this study examined differences in two proposed psychological
      components of role redistribution (youth caregiving experiences and
      responsibilities) between youth of a parent with illness and their peers from
      'healthy' families controlling for the effects of whether a parent is ill or some
      other family member, illness type and demographics. Based on self-report
      questionnaire data, four groups of Australian children were derived from a
      community sample of 2474 youth ('healthy' family, n = 1768; parental illness, n =
      336; other family member illness (OFMI), n = 254; both parental and OFMI, n =
      116). The presence of any family member with a serious illness is associated with
      an intensification of youth caregiving experiences relative to peers from healthy
      families. This risk is elevated if the ill family member is a parent, if more
      illnesses are present and by certain youth and family demographics, and
      especially by higher caregiving responsibilities. The presence of a family
      member, particularly a parent, with a serious medical condition has pervasive
      increased effects on youth caregiving compared to healthy families, and these
      effects are not fully accounted for by illness type, demographics or caregiving
      responsibilities. 

PMID- 25565078
TI  - Do capillary dried blood spot concentrations of gamma-hydroxybutyric acid mirror
      those in venous blood? A comparative study.
AB  - Gamma-hydroxybutyric acid (GHB) is a well-known illicit club and date-rape drug.
      Dried blood spot (DBS) sampling is a promising alternative for classical venous
      sampling in cases of (suspected) GHB intoxication since it allows rapid sampling,
      which is of interest for the extensively metabolized GHB. However, there is
      limited data if -and how- capillary DBS concentrations correlate with venous
      concentrations. We conducted a comparative study in 50 patients with suspected
      GHB intoxication, to determine and to correlate GHB concentrations in venous DBS
      (vDBS) and capillary DBS (cDBS). This is the first study that evaluates in a
      large cohort the correlation between capillary and venous concentrations of an
      illicit drug in real-life samples. Of the 50 paired samples, 7 were excluded: the
      vDBS concentration was below the LLOQ of 2 ug/mL in 3 cases and 4 samples were
      excluded after visual inspection of the DBS. Bland-Altman analysis revealed a
      mean % difference of -2.8% between cDBS and vDBS concentrations, with the zero
      value included in the 95% confidence interval of the mean difference in GHB
      concentration. A paired sample t-test confirmed this observation (p = 0.17). Also
      the requirement for incurred sample reproducibility was fulfilled: for more than
      two-thirds of the samples the concentrations obtained in cDBS and those in vDBS
      were within 20% of their mean. Since equivalent concentrations were observed in
      cDBS and vDBS, blood obtained by fingerprick can be considered a valid
      alternative for venous blood for GHB determination.

PMID- 25565079
TI  - Inference of median difference based on the Box-Cox model in randomized clinical
      trials.
AB  - In randomized clinical trials, many medical and biological measurements are not
      normally distributed and are often skewed. The Box-Cox transformation is a
      powerful procedure for comparing two treatment groups for skewed continuous
      variables in terms of a statistical test. However, it is difficult to directly
      estimate and interpret the location difference between the two groups on the
      original scale of the measurement. We propose a helpful method that infers the
      difference of the treatment effect on the original scale in a more easily
      interpretable form. We also provide statistical analysis packages that
      consistently include an estimate of the treatment effect, covariance adjustments,
      standard errors, and statistical hypothesis tests. The simulation study that
      focuses on randomized parallel group clinical trials with two treatment groups
      indicates that the performance of the proposed method is equivalent to or better
      than that of the existing non-parametric approaches in terms of the type-I error
      rate and power. We illustrate our method with cluster of differentiation 4 data
      in an acquired immune deficiency syndrome clinical trial.

PMID- 25565080
TI  - Adnexal mass in the postmenopausal patient.
AB  - The adnexal mass in a postmenopausal patient poses an important diagnostic and
      management dilemma for primary care providers and gynecologists. Postmenopausal
      women are at a significantly increased risk of gynecologic malignancy; yet even
      in this population the majority of adnexal masses are benign. Evaluation and
      management of these lesions centers on the identification of malignancy,
      especially ovarian cancer, while avoiding unnecessary intervention in patients
      with benign lesions. Tumor markers and imaging can help in the evaluation of
      adnexal mass in postmenopausal women. Transvaginal ultrasound has long been
      considered the imaging modality of choice for the evaluation of adnexal masses.
      Particularly in the setting of high frequency utilization of transvaginal probes,
      which project high quality images allowing for detailed descriptions of the
      macroscopic appearance of the mass, and remains the least expensive of all
      imaging modalities currently available. For adnexal masses that are highly
      suspicious for cancer, women should be referred a gynecologic oncologist and
      facility for optimal care. 

PMID- 25565081
TI  - Sexually transmitted diseases.
AB  - Sexually transmitted diseases (STDs) continue to be a global epidemic with
      significant risk of morbidity/mortality for the fetus. STDs with prominent
      cutaneous findings including condylomata acuminata, genital herpes infections,
      and syphilis are reviewed. Important clinical cutaneous findings help aid early
      diagnosis and facilitate treatment. Condylomata acuminata have the potential of
      causing cervical cancer, anogenital cancer, and oropharyngeal cancer. Significant
      advances have been made in human papilloma virus vaccinations and treatment.
      Genital herpes infection can produce significant physical and emotional distress
      to the patient and significant potential harm to the fetus. Early clinical
      recognition of STDs and their appropriate management is critical. 

PMID- 25565083
TI  - Electrophilic amination of fluoroalkyl groups on azodicarboxylate derivatives.
AB  - The formation of an NCF3 bond or an NCF2R bond still remains scarce. An efficient
      direct electrophilic amination of fluoroalkyl groups was developed.
      Difluoroenoxysilanes reacted easily on azodicarboxylate derivatives. These
      results led to a novel family of NCF3 and NCF2 hydrazine derivatives. 

PMID- 25565082
TI  - Loss of miRNAs during processing and storage of cow's (Bos taurus) milk.
AB  - MicroRNAs (miRs, miRNAs) play central roles in gene regulation. Previously, we
      reported that miRNAs from pasteurized, store-bought bovine milk have biological
      activity in humans. Here, we assessed the effects of milk processing, storage,
      somatic cell content, and handling by consumers on the degradation of miRNAs in
      milk; we also quantified miRNAs in dairy products. Pasteurization and
      homogenization caused a 63% loss of miR-200c, whereas a 67% loss observed for miR
      29b was statistically significant only in skim milk. Effects of cold storage and
      somatic cell content were quantitatively minor (<2% loss). Heating in the
      microwave caused a 40% loss of miR-29b but no loss of miR-200c. The milk fat
      content had no effect on miRNA stability during storage and microwave heating.
      The concentrations of miRNAs in dairy products were considerably lower than in
      store-bought milk. We conclude that processing of milk by dairies and handling by
      consumers causes a significant loss of miRNAs. 

PMID- 25565084
TI  - Dyadic Effects of Individual and Friend on Physical Activity in College Students.
AB  - OBJECTIVE: Physical activity (PA) tends to decline throughout the college years,
      and close friends' influence is known to be an important factor in maintaining
      PA. This study examined the actor effect and partner effect between an individual
      and his/her friend regarding the influence of self-efficacy and social support on
      PA among Korean college students. DESIGN AND SAMPLE: Cross-sectional survey data
      from 108 pairs of individual students and friends were analyzed. MEASURES: The
      survey questionnaire measured PA, self-efficacy toward exercise, social support
      for PA, anxiety and depression, community environments, and perceived health
      status. Structural equation modeling with path analysis was conducted to test
      Actor-Partner Interdependence Model (APIM) explaining close relationships on PA.
      RESULTS: One-sided partner effect that friends' perceived friend support was
      directly related to individual's PA (beta = 0.20, p < .05) was revealed.
      Regarding actor effects, self-efficacy was directly related to higher levels of
      PA for individual and friend. Perceived health status was related to higher level
      of individuals' PA. CONCLUSIONS: These results suggest a role for public health
      nurses in developing interventions for college-aged young adults that promotes
      friend support for PA as well as individual self-efficacy toward PA, to engage
      young adults in establishing lifelong health-promoting PA.

PMID- 25565085
TI  - Infectious bursal disease virus uptake involves macropinocytosis and trafficking
      to early endosomes in a Rab5-dependent manner.
AB  - Infectious bursal disease virus (IBDV) internalization is sparsely known in terms
      of molecular components of the pathway involved. To describe the cell biological
      features of IBDV endocytosis, we employed perturbants of endocytic pathways such
      as pharmacological inhibitors and overexpression of dominant-negative mutants.
      Internalization analysis was performed quantifying infected cells by
      immunofluorescence and Western blot detection of the viral protein VP3 at 12 h
      post-infection reinforced by the analysis of the capsid protein VP2 localization
      after virus uptake at 1 h post-infection. We compared IBDV infection to the
      internalization of well-established ligands with defined endocytic pathways:
      transferrin, cholera-toxin subunit B and dextran. To describe virus endocytosis
      at the morphological level, we performed ultrastructural studies of viral
      internalization kinetics in control and actin dynamics-blocked cells. Our results
      indicate that IBDV endocytic internalization was clathrin- and dynamin
      independent, and that IBDV uses macropinocytosis as the primary entry mechanism.
      After uptake, virus traffics to early endosomes and requires exposure to the low
      endocytic pH as well as a functional endocytic pathway to complete its
      replication cycle. Moreover, our results indicate that the GTPase Rab5 is crucial
      for IBDV entry supporting the participation of the early endosomal pathway in
      IBDV internalization and infection of susceptible cells.

PMID- 25565086
TI  - Surface-orientation-dependent distribution of subsurface cation-exchange defects
      in olivine-phosphate nanocrystals.
AB  - Atomic-scale exchange between two different cations of similar size in
      crystalline oxides is one of the major types of point defects when multiple
      cations in oxygen interstitials are arrayed in an ordered manner. Although a
      number of studies have been performed on a variety of Li-intercalation olivine
      phosphates to determine the distribution of exchange defects in bulk,
      understanding of the thermodynamic stability of the defects in subsurface regions
      and its dependency on the crystallographic orientation at the surface has
      remained elusive. Through a combination of small-angle neutron scattering, atomic
      scale direct probing with scanning transmission electron microscopy, and
      theoretical ab initio calculations, we directly demonstrate that the antisite
      exchange defects are distributed in a highly anisotropic manner near the surfaces
      of LiFePO4 crystals. Moreover, a substantial amount of cation exchanges between
      Li and Fe sites is identified as an energetically favorable configuration in some
      surface regions, showing excellent agreement with the calculation results of
      negative defect formation energies. The findings in this study provide insight
      into developing better ways to avoid degradation of lithium mobility through the
      surface as well as scientifically notable features regarding the distribution of
      exchange defects in olivine phosphates. 

PMID- 25565087
TI  - Reaction of tungsten-phosphinidene and -arsinidene complexes with carbodiimides
      and alkyl azides: a straightforward way to four-membered heterocycles.
AB  - The reaction of the phosphinidene and arsinidene complexes [Cp*E{W(CO)5 }2 ] (E=P
      (1 a), As (1 b); Cp*=C5 Me5 ) with carbodiimides leads to the new four-membered
      heterocycles of the type [Cp*C(NR)2 E{W(CO)5 }2 ] (E=P: R=iPr (2 a), Cy (3 a);
      E=As: R=iPr (2 b), Cy (3 b)). The reaction of phosphinidene complex 1 a with
      alkyl azides yields the triazaphosphete derivatives [Cp*P{W(CO)5 }N(R)NN{W(CO)5
      }] (R=Hex, Cy) (4). These unprecedented N3 P four-membered triazaphosphete
      complexes can be regarded as stabilized intermediates of the Staudinger reaction,
      which have not been previously isolated. All of the isolated products were
      characterized by NMR, IR spectroscopy, mass spectrometry, and by single-crystal X
      ray diffraction analysis. 

PMID- 25565088
TI  - Determinants of adherence to diabetes treatment.
AB  - BACKGROUND: Understanding and improving medication adherence is crucial in
      diabetes management. Adherence to a diabetes regimen can improve glucose control
      and limit the development of complications. The aim of the present study was to
      evaluate the extent to which a variety of factors influence diabetes medication
      adherence. METHODS: A medication adherence survey was made available on WebMD, a
      medical information website for patients and/or consumers. Respondents were
      residents of the US, >=18 years old, and diagnosed with either type 1 or type 2
      diabetes mellitus (self-reported). RESULTS: Behavioral adherence (self-reported
      doses missed per week) correlated with perceived adherence (patients' self-report
      of their overall impression of medication adherence, ranked 0-5; P < 0.001).
      Adherent patients (very few [0%-10%] issues with adherence) were more likely to
      report having received information from their physician. Mostly adherent patients
      (few [11%-26%] issues with adherence) were less likely to obtain information from
      their physician, but reported more medication self-titration. Somewhat non
      adherent patients (some [27%-46%] adherence issues) reported more "self
      consciousness factors" and hypoglycemia. Non-adherent patients (many [47%-88%]
      adherence issues) were more likely to report worries about medication side
      effects. CONCLUSIONS: Receiving information from a healthcare provider is
      associated with greater diabetes medication adherence, suggesting the importance
      of clinicians making time to provide patient education.

PMID- 25565093
TI  - Total Testosterone and Calculated Estimates for Free and Bioavailable
      Testosterone: Influence of Age and Body Mass Index and Establishment of Sex
      Specific Reference Ranges.
AB  - Measurement of sex steroids is required to evaluate gonadal function, but
      normative data are lacking (especially for estimates of physiologically active
      testosterone). Using modern immunoassays, this study established sex-specific
      reference ranges (2.5% and 97.5% percentiles) for total testosterone (TOT),
      bioactive testosterone Vermeulen (BTV), free androgen index (FAI), free
      testosterone Sartorius (FTS), free testosterone Vermeulen (FTV), and sex hormone
      binding globulin (SHBG). In the comparative study, subjects were grouped by age
      (18-30; 31-50; >50 years), BMI (<25; 25-30; >30 kg/m(2)), and sex. Study
      participants were selected in such a way that each group comprised 12 subjects
      (e.g., 12 males between 18 and 30 years with a BMI of <25 kg/m(2), and so on),
      resulting in a total of 216 controls (108 males, 108 females; age: 40.3 +/- 1.0;
      BMI: 27.8 +/- 0.4). Multiple stepwise regression analyses were performed
      (covariates: age, BMI, sex), and sex-specific reference ranges were applied to 50
      males (age: 46.1 +/- 2.3; BMI: 27.4 +/- 0.7) with suspected hypogonadism.
      Regression analysis identified the strongest predictor of each parameter apart
      from sex, resulting in age-specific (males: FAI, SHBG, BTV, FTV; females: TOT,
      FTS, SHBG), BMI-specific (males: TOT, FTS; females: FAI, BTV, FTV) and overall
      cutoffs for both sexes. In male patients, overall agreement between the results
      derived from the estimates (i.e., BTV, FTS, FTV) was high (with discordant
      results in only 4%). In summary, if both the endocrine workup and the clinical
      presentation were taken into account, the newly established reference ranges
      allowed reliable identification of hypogonadal males.

PMID- 25565094
TI  - Increased Maternal Serum Interleukin-6 Concentrations at 11 to 14 Weeks of
      Gestation in Low Risk Pregnancies Complicated with Gestational Diabetes Mellitus:
      Development of a Prediction Model.
AB  - The aim of the study was to examine interleukin-6 (IL-6) maternal serum
      concentration at 11 to 14 gestational weeks in normal pregnancies and pregnancies
      complicated by gestational diabetes mellitus (GDM) and to create first trimester
      prediction models for GDM. Case-control study conducted in a Fetal Medicine Unit.
      Study population included 40 GDM cases and 94 controls. Maternal characteristics,
      first trimester ultrasound markers, biochemical indices, and IL-6 levels were
      used for our analysis. IL-6 was related to maternal weight among the maternal
      characteristics, (R(2)=0.0679, p=0.01). IL-6 was increased (p=0.001) in the GDM
      group (median=2 pg/ml) compared to the control group (median=1.5 pg/ml) even
      after adjustment for maternal weight. IL-6 was inversely related to birth weight
      adjusted for gestational age at delivery (r=-0.3382, p<0.001) and glucose levels
      at oral glucose test. Maternal weight and age were the only predictors of GDM
      among the maternal characteristics [Detection Rate (DR)=59.4%; for 25% False
      Positive Rate (FPR); Area Under the Curve (AUC)=0.7291; Model R(2)=0.1096,
      p<0.001]. IL-6 alone was a significant predictor of GDM (DR=51.3%; for 25% FPR;
      AUC=0.6731; Model R(2)=0.0616, p<0.001). Combination of maternal characteristics
      with IL-6 yielded an improved prediction (DR=67.5%; for 25% FPR; AUC=0.7586;
      Model R(2)=0.1521, p<0.001). IL-6 concentrations are increased at 11-14 weeks in
      pregnancies with GDM. Combination of maternal characteristics and maternal serum
      IL-6 levels may provide effective first trimester screening for GDM. 

PMID- 25565095
TI  - Sex hormone binding globulin and risk of breast cancer in postmenopausal women: a
      meta-analysis of prospective studies.
AB  - Previous studies on the association between sex hormone binding globulin (SHBG)
      level and risk of breast cancer in postmenopausal women reported conflicting
      results. A meta-analysis of prospective studies was performed to evaluate the
      association between SHBG level and risk of breast cancer in postmenopausal women.
      Pubmed (1980 to July 2014) and EMBASE (1988 to July 2014) were searched for
      eligible studies. Eligible studies were prospective cohort or nested case-control
      studies on the association between SHBG level and risk of breast cancer in
      postmenopausal women. Meta-analysis using random-effects model was performed to
      calculate the pooled risk ratios (RRs) with 95% confidence intervals (95% CIs).
      Of 946 studies identified, 26 prospective studies from 21 publications were
      finally included in the meta-analysis. In postmenopausal women, the pooled RR for
      breast cancer comparing highest with lowest categories of SHBG was 0.64 (95% CI
      0.57-0.72, p<0.001, I(2)=6.5%). The pooled RRs were not obviously altered in the
      sensitivity analyses and subgroup analyses. In cumulative meta-analysis, a more
      significant association between SHBG level and risk of breast cancer in
      postmenopausal women was observed as evidence accumulated by publication year.
      There was no obvious risk of publication bias. High SHBG level is significantly
      associated with decreased risk of breast cancer in postmenopausal women, and it's
      a protective factor of breast cancer in postmenopausal women. 

PMID- 25565096
TI  - Serum progranulin concentrations are not responsive during oral lipid tolerance
      test and oral glucose tolerance test.
AB  - The postprandial regulation of progranulin by oral uptake of lipids and
      carbohydrates in healthy individuals has not yet been investigated. The
      regulation of progranulin in 2 large cohorts of healthy volunteers during oral
      lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100)
      was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an
      outpatient setting. Venous blood was drawn at 0 hours (h) (fasting) and at 2, 4,
      and 6 h in OLTT or 1 and 2 h in OGTT. A novel OLTT solution completely free of
      carbohydrates and protein was applied. Subjects were characterized by
      anthropometric and laboratory parameters. Serum concentrations of progranulin
      were measured by enzyme-linked immunosorbent assay (ELISA). Circulating
      progranulin levels remained unchanged during OLTT and OGTT. Fasting progranulin
      levels ranged between 31.3+/-8.7 and 40.6+/-7.7 ng/ml and were not different in
      subgroups addressing BMI, gender, family history, smoking habits, and hormonal
      contraception. There was a reciprocal correlation of progranulin with HDL
      (negative) and LDL cholesterol levels (positive). In healthy adults, fasting and
      postprandial circulating progranulin levels are not different in BMI subgroups.
      Oral uptake of carbohydrates and lipids does not influence circulating
      progranulin levels in a short-term manner. A postprandial and short-term
      regulation of this adipokine is absent, at least in healthy subjects. There is a
      negative correlation of progranulin with HDL cholesterol, but a positive
      correlation with LDL cholesterol. This reciprocal association might be of
      physiological importance for an individual's atherosclerotic risk. 

PMID- 25565097
TI  - Differential regulation of oxytocin receptor in various adipose tissue depots and
      skeletal muscle types in obese Zucker rats.
AB  - Multifunctional peptide oxytocin currently undergoes intensive research due to
      its proposed anti-obesity properties. Until now, little is known about regulation
      of oxytocin receptor in metabolically active tissues in obesity. The aim of the
      present study was to measure expression of oxytocin receptor upon obese phenotype
      with respect to the variety among adipose tissue and skeletal muscles with
      distinct anatomical localisation. Total homogenates were prepared from
      epididymal, retroperitoneal and inguinal adipose tissues as well as quadriceps
      and soleus muscle from lean and obese Zucker rats. Oxytocin receptor protein was
      determined by immunoblot. Interestingly, elevated oxytocin receptor was observed
      in epididymal adipose tissue of obese rats in contrast to its downregulation in
      subcutaneous and no change in retroperitoneal fat. In lean animals, oxytocin
      receptor protein was expressed at similar levels in all adipose depots. This
      uniformity was not observed in the case of skeletal muscle in which fibre type
      composition seems to be determinant of oxytocin receptor expression. Quadriceps
      muscle with the predominance of glycolytic fibres exhibits higher oxytocin
      receptor expression than almost exclusively oxidative soleus muscle. Oxytocin
      receptor protein levels were decreased in both skeletal muscles analysed upon
      obese phenotype. The present work demonstrates that even under identical
      endocrine circumstances, oxytocin receptor is differentially regulated in adipose
      tissue of obese rats depending on fat depot localisation. These results also
      imply which tissues may be preferentially targeted by oxytocin treatment in
      metabolic disease. 

PMID- 25565098
TI  - Monitoring exposure of brown bullheads and benthic macroinvertebrates to sediment
      contaminants in the Ashtabula River before, during, and after remediation.
AB  - In 2007, approximately 420,500 cubic meters of contaminated sediment were removed
      from the Ashtabula River by dredging. The primary objective of the present study
      was to monitor contaminant exposure in fish and macroinvertebrates before,
      during, and after dredging. This was done by measuring tissue concentrations of
      polychlorinated biphenyl (PCB) and polycyclic aromatic hydrocarbon (PAH) in brown
      bullhead catfish (Ameriurus nebulosa) and in benthic macroinvertebrates,
      assessing changes in DNA damage in fish liver and blood, and scoring external and
      histopathological lesions and anomalies in the fish. In surficial sediment PCBs
      and PAHs were also quantified in conjunction with the biological sampling. The
      results show a significant reduction in contaminant levels in both fish and
      macroinvertebrates following dredging, indicating the effectiveness of the
      remediation in reducing exposure of biota to the primary contaminants of concern.
      Similarly, DNA damage levels in fish collected from the Ashtabula River
      significantly declined following dredging; however, a similar reduction in DNA
      damage over time was seen in fish collected from a reference site (Conneaut
      Creek), making interpretation difficult. Macroinvertebrate PCB concentrations
      were reflective of the sediment concentrations in the areas where Hester-Dendy
      samplers were deployed for macroinvertebrate collection. The present study
      demonstrates that these methods can be used to evaluate and assess the
      effectiveness of remediation techniques at contaminated sediment sites.

PMID- 25565099
TI  - Credibility and reproducibility.

PMID- 25565100
TI  - Symmetry breaking in homo-oligomers: the curious case of mega-hemocyanin.
AB  - Mega-hemocyanin is a 13.5 MDa oxygen transporter found in snails. It is built
      from three stacked rings involving ten subunits each. The cryo-EM structure of
      the complex presented by Gatsogiannis and colleagues in this issue of Structure
      revealed an unexpected breaking of 5-fold symmetry in the central ring and a
      nonequivalent packing of the subunits. 

PMID- 25565101
TI  - Renaissance of MMPs as therapeutic targets? Maybe.
AB  - Matrix metalloproteases (MMPs) have been implicated in a number of different
      human diseases and are currently one of the actively pursued targets in drug
      discovery and development. In this issue of Structure, Udi and colleagues
      describe how an inhibitory antibody, LEM-2/15, affects a member of the MMP
      family, MT1-MMP. 

PMID- 25565102
TI  - It takes two to rule translation elongation.
AB  - In this issue of Structure, Glatt and colleagues report the structure of the
      Kti11/Kti13 heterodimer. This study reveals how dimerization and Fe(2+) binding
      are required for modification of both tRNA and EF2, thus suggesting a mechanism
      for regulation of translation elongation via two different pathways. 

PMID- 25565103
TI  - Unraveling structural polymorphism of amyloid fibers.
AB  - Amyloid fibers are self-assembling cross beta sheet structures whose overall
      molecular architecture is highly variable. In this issue of Structure, Torreira
      and colleagues use electron microscopy to resolve ultrastructural polymorphisms
      of RepA-WH1 amyloids. 

PMID- 25565104
TI  - A new test of computational protein design: predicting posttranslational
      modification specificity for the enzyme SMYD2.
AB  - In this issue of Structure, Lanouette and colleagues use a combination of
      computation and experiment to define a specificity motif for the lysine
      methyltransferase SMYD2. Using this motif, they predict and experimentally verify
      four new SMYD2 substrates. 

PMID- 25565105
TI  - A hinge migration mechanism unlocks the evolution of green-to-red photoconversion
      in GFP-like proteins.
AB  - In proteins, functional divergence involves mutations that modify structure and
      dynamics. Here we provide experimental evidence for an evolutionary mechanism
      driven solely by long-range dynamic motions without significant backbone
      adjustments, catalytic group rearrangements, or changes in subunit assembly.
      Crystallographic structures were determined for several reconstructed ancestral
      proteins belonging to a GFP class frequently employed in superresolution
      microscopy. Their chain flexibility was analyzed using molecular dynamics and
      perturbation response scanning. The green-to-red photoconvertible phenotype
      appears to have arisen from a common green ancestor by migration of a knob-like
      anchoring region away from the active site diagonally across the beta barrel
      fold. The allosterically coupled mutational sites provide active site
      conformational mobility via epistasis. We propose that light-induced chromophore
      twisting is enhanced in a reverse-protonated subpopulation, activating internal
      acid-base chemistry and backbone cleavage to enlarge the chromophore. Dynamics
      driven hinge migration may represent a more general platform for the evolution of
      novel enzyme activities. 

PMID- 25565106
TI  - Single-molecule FRET reveals hidden complexity in a protein energy landscape.
AB  - Here, using single-molecule FRET, we reveal previously hidden conformations of
      the ankyrin-repeat domain of AnkyrinR, a giant adaptor molecule that anchors
      integral membrane proteins to the spectrin-actin cytoskeleton through
      simultaneous binding of multiple partner proteins. We show that the ankyrin
      repeats switch between high-FRET and low-FRET states, controlled by an
      unstructured "safety pin" or "staple" from the adjacent domain of AnkyrinR.
      Opening of the safety pin leads to unravelling of the ankyrin repeat stack, a
      process that will dramatically affect the relative orientations of AnkyrinR
      binding partners and, hence, the anchoring of the spectrin-actin cytoskeleton to
      the membrane. Ankyrin repeats are one of the most ubiquitous molecular
      recognition platforms in nature, and it is therefore important to understand how
      their structures are adapted for function. Our results point to a striking
      mechanism by which the order-disorder transition and, thereby, the activity of
      repeat proteins can be regulated. 

PMID- 25565107
TI  - Protist-facilitated particle transport using emulated soil micromodels.
AB  - Microbial processes in the subsurface can be visualized directly using
      micromodels to emulate pore-scale geometries. Here, emulated soil micromodels
      were used to measure transport of fluorescent beads in the presence and absence
      of the soil ciliate Colpoda sp. under quiescent conditions. Beads alone or beads
      with protists were delivered to the input wells of replicate micromodels that
      contained three 20 mm(2) channels emulating a sandy loam microstructure. Bead
      abundance in microstructured channels was measured by direct counts of tiled
      confocal micrographs. For channels with protists, average bead abundances were
      approximately 320, 560, 710, 830, and 790 mm(-2) after 1, 2, 3, 5, and 10 days,
      respectively, versus 0, 0, 0.3, 7.8, and 45 mm(-2) without protists. Spatial and
      temporal patterns of bead abundance indicate that protist-facilitated transport
      is not a diffusive-type process but rather a function of more complex protist
      behaviors, including particle uptake and egestion and motility in a
      microstructured habitat. Protist-facilitated transport may enhance particle
      mixing in the soil subsurface and could someday be used for targeted delivery of
      nanoparticles, encapsulated chemicals, or bacteria for remediation and
      agriculture applications. 

PMID- 25565109
TI  - Going the extra mile.

PMID- 25565108
TI  - The flavone eupatilin inhibits eotaxin expression in an NF-kappaB-dependent and
      STAT6-independent manner.
AB  - The CC chemokine eotaxin contributes to epithelium-induced inflammation in airway
      diseases such as asthma. Eupatilin (5,7-dihydroxy-3',4',6'-trimethoxyflavone), a
      bioactive component of Artemisia asiatica Nakai (Asteraceae), is reported to
      inhibit the adhesion of eosinophils to bronchial epithelial cells. However,
      little is known about the molecular mechanism of eupatilin-induced attenuation of
      bronchial epithelium-induced inflammation. In this study, we investigated the
      effect of eupatilin on expression of eotaxin-1 (CCL11), a potent chemoattractant
      for eosinophils. Eupatilin significantly inhibited eotaxin expression in
      bronchial epithelial cells stimulated with TNF-alpha, while NF-kappaB and
      IkappaBalpha kinase (IKK) activities declined concurrently. Eupatilin also
      inhibited mitogen-activated protein kinase (MAPK) activity; however, all of these
      anti-inflammatory activities were reversed by MAPK overexpression. In contrast,
      eupatilin did not affect the signal transducer and activator of transcription 6
      (STAT6) signalling in bronchial epithelial cells stimulated with IL-4.
      Furthermore, eupatilin significantly attenuated TNF-alpha-induced eosinophil
      migration. These results suggest that the eupatilin inhibits the signalling of
      MAPK, IKK, NF-kappaB and eotaxin-1 in bronchial epithelial cells, leading to
      inhibition of eosinophil migration. 

PMID- 25565110
TI  - Soy Protein Isolate Inhibits High Fat Diet-Induced Senescence Pathways in
      Osteoblasts to Maintain Bone Acquisition in Male Rats.
AB  - Chronic consumption by experimental animals of a typical Western diet high in
      saturated fats and cholesterol during postnatal life has been demonstrated to
      impair skeletal development. However, underlying mechanism by which high fat,
      energy dense diets affect bone forming cell phenotypes is poorly understood.
      Here, we show that male weanling rats fed a diet containing 45% fat and 0.5%
      cholesterol made with casein (HF-Cas) for 6 weeks displayed lower bone mineral
      density and strength compared to AIN-93G-fed dietary controls. Substitution of
      casein with soy protein isolate (SPI) in the high fat diet (HF-SPI) prevented
      these effects. The bone sparing effects of SPI were associated with prevention of
      HF-Cas-induced osteoblast senescence pathways through suppression of p53/p21
      signaling pathways. HF-Cas-fed rats had increased caveolin-1 and down-regulated
      Sirt1 leading to activations of PPARgamma and p53/p21; whereas, rats fed HF-SPI
      suppressed caveolin-1and activated Sirt1 to de-acetylate PPARgamma and p53 in
      bone. Treatment of osteoblastic cells with non-esterified free fatty acid (NEFA)
      increased cell senescence signaling pathways. Isoflavones significantly blocked
      activations of senescence-associated beta-galactosidase and PPARgamma/p53/p21 by
      NEFA. Finally, replicative senescent osteoblastic cells and bone marrow
      mesenchymal ST2 cells exhibited similar behavior to cells treated with NEFA and
      in vivo bone cells in rats fed HF-Cas diet. These results suggest that: 1) high
      concentrations of NEFA occurring with HF intake are mediators of osteoblast cell
      senescence leading to impairment of bone development and acquisition; 2) the
      molecular mechanisms underlying the SPI-protective effects involve isoflavone
      induced inhibition of osteoblastic cell senescence to prevent HF-induced bone
      impairments.

PMID- 25565111
TI  - Three-dimensional nitrogen-doped graphene as an ultrasensitive electrochemical
      sensor for the detection of dopamine.
AB  - Three-dimensional nitrogen-doped graphene (3D N-doped graphene) was prepared
      through chemical vapor deposition (CVD) by using porous nickel foam as a
      substrate. As a model, a dopamine biosensor was constructed based on the 3D N
      doped graphene porous foam. Electrochemical experiments exhibited that this
      biosensor had a remarkable detection ability with a wide linear detection range
      from 3 * 10(-6) M to 1 * 10(-4) M and a low detection limit of 1 nM. Moreover,
      the fabricated biosensor also showed an excellent anti-interference ability,
      reproducibility, and stability. 

PMID- 25565112
TI  - Sulphur-impregnated flow cathode to enable high-energy-density lithium flow
      batteries.
AB  - Redox flow batteries are promising technologies for large-scale electricity
      storage, but have been suffering from low energy density and low volumetric
      capacity. Here we report a flow cathode that exploits highly concentrated sulphur
      impregnated carbon composite, to achieve a catholyte volumetric capacity 294 Ah
      l(-1) with long cycle life (>100 cycles), high columbic efficiency (>90%, 100
      cycles) and high energy efficiency (>80%, 100 cycles). The demonstrated catholyte
      volumetric capacity is five times higher than the all-vanadium flow batteries (60
      Ah l(-1)) and 3-6 times higher than the demonstrated lithium-polysulphide
      approaches (50-117 Ah l(-1)). Pseudo-in situ impedance and microscopy
      characterizations reveal superior electrochemical and morphological reversibility
      of the sulphur redox reactions. Our approach of exploiting sulphur-impregnated
      carbon composite in the flow cathode creates effective interfaces between the
      insulating sulphur and conductive carbon-percolating network and offers a
      promising direction to develop high-energy-density flow batteries.

PMID- 25565113
TI  - Coarse-grained molecular dynamics simulation of self-assembly and surface
      adsorption of ionic surfactants using an implicit water model.
AB  - We perform coarse-grained molecular dynamics simulations for sodium dodecyl
      sulfate (SDS) surfactant using a modification of the Dry Martini force field
      (Arnarez et al. 2014) with implicit water. After inclusion of particle mesh Ewald
      (PME) electrostatics, an artificially high dielectric constant for water
      (epsilon(r) = 150), and reparameterization, we obtain structural and
      thermodynamic properties of SDS micelles that are close to those obtained from
      the standard Martini force field with explicit water, which in turn match those
      of atomistic simulations. The gains in computational efficiency obtained by
      removing explicit water allow direct simulations of the self-assembly of SDS in
      solution. We observe surfactant exchange among micelles and micelle fission and
      fusion and obtain realistic, equilibrated micelle size distributions at modest
      computational cost, as well as a transition to cylindrical micelles at high
      surfactant concentration or with added salt. We further apply this parametrized
      force field to study the adsorption of SDS onto hydrophobic surfaces and
      calculate the adsorption kinetics and equilibrium adsorption isotherm. The
      greatly increased speed of computation of surfactant self-assembly made possible
      by this Dry Martini method should allow future simulation of competitive
      adsorption of multiple surfactant species to surfaces, as well as simulation of
      micellar shape transitions.

PMID- 25565115
TI  - Re/creating entrepreneurs of the self: discourses of worker and employee 'value'
      and current vocational rehabilitation practices.
AB  - Vocational rehabilitation for people experiencing work disability is a social
      practice often situated within health services, but the social and political
      drivers and effects of this practice are rarely critically analysed in health
      research or policy. In this study we used a Foucauldian theoretical perspective
      to analyse the ways in which current vocational rehabilitation practices in New
      Zealand re/produce notions of worker and employee 'value', and how different
      approaches to vocational rehabilitation deploy current discourses about value. We
      also consider the subject positions produced through these different approaches
      and the identities and actions they make possible for people experiencing work
      disability. The analysis showed that notions about the importance of worker and
      employee value in a job market are pervasive in vocational rehabilitation, and
      reflect wider societal discourses. However, the deployment of those discourses in
      different approaches to vocational rehabilitation practice are diverse, producing
      different opportunities and constraints for people experiencing disability. We
      argue that an examination of these various opportunities and constraints at the
      level of practice approaches is important, as considerable time and resources are
      allocated to developing solutions to help those who do not thrive in the current
      systems, yet we rarely critique the premises on which the systems are based. 

PMID- 25565114
TI  - Exploring the spatial dimension of estrogen and progesterone signaling: detection
      of nuclear labeling in lobular epithelial cells in normal mammary glands adjacent
      to breast cancer.
AB  - BACKGROUND: Comprehensive spatial assessment of hormone receptor
      immunohistochemistry staining in digital whole slide images of breast cancer
      requires accurate detection of positive nuclei within biologically relevant
      regions of interest. Herein, we propose a combination of automated region
      labeling at low resolution and subsequent detailed tissue evaluation of
      subcellular structures in lobular structures adjacent to breast cancer, as a
      proof of concept for the approach to analyze estrogen and progesterone receptor
      expression in the spatial context of surrounding tissue. METHODS: Routinely
      processed paraffin sections of hormone receptor-negative ductal invasive breast
      cancer were stained for estrogen and progesterone receptor by
      immunohistochemistry. Digital whole slides were analyzed using commercially
      available image analysis software for advanced object-based analysis, applying
      textural, relational, and geometrical features. Mammary gland lobules were
      targeted as regions of interest for analysis at subcellular level in relation to
      their distance from coherent tumor as neighboring relevant tissue compartment.
      Lobule detection quality was evaluated visually by a pathologist. RESULTS: After
      rule set optimization in an estrogen receptor-stained training set, independent
      test sets (progesterone and estrogen receptor) showed acceptable detection
      quality in 33% of cases. Presence of disrupted lobular structures, either by
      brisk inflammatory infiltrate, or diffuse tumor infiltration, was common in cases
      with lower detection accuracy. Hormone receptor detection tended towards higher
      percentage of positively stained nuclei in lobules distant from the tumor border
      as compared to areas adjacent to the tumor. After adaptations of image analysis,
      corresponding evaluations were also feasible in hormone receptor positive breast
      cancer, with some limitations of automated separation of mammary epithelial cells
      from hormone receptor-positive tumor cells. CONCLUSIONS: As a proof of concept
      for object-oriented detection of steroid hormone receptors in their spatial
      context, we show that lobular structures can be classified based on texture-based
      image features, unless brisk inflammatory infiltration disrupts the normal
      morphological structure of the tubular gland epithelium. We consider this
      approach as prototypic for detection and spatial analysis of nuclear markers in
      defined regions of interest. We conclude that advanced image analysis at this
      level of complexity requires adaptation to the individual tumor phenotypes and
      morphological characteristics of the tumor environment.

PMID- 25565116
TI  - Standing wave plasmon modes interact in an antenna-coupled nanowire.
AB  - In a standing wave optical cavity, the coupling of cavity modes, for example,
      through a nonlinear medium, results in a rich variety of nonlinear dynamical
      phenomena, such as frequency pushing and pulling, mode-locking and pulsing, modal
      instabilities, even complex chaotic behavior. Metallic nanowires of finite length
      support a hierarchy of longitudinal surface plasmon modes with standing wave
      properties: the plasmonic analog of a Fabry-Perot cavity. Here we show that
      positioning the nanowire within the gap of a plasmonic nanoantenna introduces a
      passive, hybridization-based coupling of the standing-wave nanowire plasmon modes
      with the antenna structure, mediating an interaction between the nanowire plasmon
      modes themselves. Frequency pushing and pulling, and the enhancement and
      suppression of specific plasmon modes, can be controlled and manipulated by
      nanoantenna position and shape. 

PMID- 25565117
TI  - Automated image analysis in the study of lymphocyte subpopulation in eosinophilic
      oesophagitis.
AB  - BACKGROUND: Eosinophilic oesophagitis (EoE) is characterized by the presence of
      eosinophils in oesophageal mucosa. Other inflammatory cells, mainly lymphocytes,
      dendritic cells, and mast cells may also play an important role in this disease.
      The aim of this study is to compare the inflammatory pattern of the mucosa
      between EoE and gastro-oesophageal reflux disease (GERD), using automatic image
      analysis in digital slides, and to assess treatment response after elimination
      diet and food challenge test. METHODS: From 2010 to 2013, 35 oesophageal biopsies
      from EoE and GERD patients were randomly selected. In six EoE biopsies, patients
      had been treated with selective food exclusion diet. Immunohistochemical study
      with CD3, CD20, CD4, and CD8 for lymphocyte populations, CD1a for dendritic
      cells, and CD117/c-kit for mast cells was performed. Slides were scanned using
      Leica Aperio Scanscope XT with 40* magnification. Immunohistochemical expression
      was quantified in 245 immunohistochemistry digital slides with Leica Aperio
      positive pixel count algorithm using two different approaches: whole slide
      analysis versus selection of a 2 mm2 hot spot area. RESULTS: Average eosinophil
      cell count was significantly higher (p < 0.001) in the first biopsy of EoE
      patients before treatment (30.75 eosinophils per high power field - HPF) than in
      GERD patients (0.85 eosinophils/HPF) or in EoE patients after treatment with
      elimination diet (1.60 eosinophils/HPF). In the immunohistochemical study, manual
      count and automatic image analysis showed a significant increase in the number of
      CD3 and CD8 cells in EoE patients, compared with GERD patients. However, the
      increase of CD117/c-kit was only statistically significant when manual counting
      procedures were used. CD20 positive cell count also showed a non-statistically
      significant tendency to reduce after elimination diet treatment. CONCLUSIONS:
      Positive pixel count algorithm can be a useful tool to quantify the
      immunohistochemical expression of inflammatory cells in the diagnosis and follow
      up of eosinophilic oesophagitis.

PMID- 25565118
TI  - Proximal subungual onychomycosis caused by Fusarium falciforme successfully cured
      with posaconazole.

PMID- 25565119
TI  - Continuation or discontinuation of antithrombotics in clinical daily practice of
      gastrointestinal endoscopy: Has a paradigm shift occurred in Japan?

PMID- 25565121
TI  - Transanal total mesorectal excision of rectal carcinoma: evidence to learn and
      adopt the technique.

PMID- 25565122
TI  - Ensuring excellence in centers of excellence programs.
AB  - Studies have found associations between better outcomes and a variety of
      structural and process criteria that help explain the wide outcome variations
      that occur across hospitals. In response, Centers of Excellence programs have
      been developed by multiple third parties. Despite this, programs have yielded
      disappointing results and can have unintended consequences. To outweigh potential
      harms, outcomes at Centers of Excellence must be clearly superior. We need to
      change how hospitals are designated and provide evidence that Centers of
      Excellence are truly excellent. 

PMID- 25565123
TI  - Achieving high-quality surgical care: observations from the American College of
      Surgeons Quality of Care Programs.

PMID- 25565124
TI  - Public reporting in surgery: an emerging opportunity to improve care and inform
      patients.

PMID- 25565125
TI  - Learning to detect, categorize, and identify skin lesions: a meta-analysis.
AB  - IMPORTANCE: Educators use a variety of practices to train laypersons, medical
      students, residents, and primary care providers to diagnose skin lesions.
      Researchers have described these methods for decades, but there have been few
      attempts to catalog their scope or effectiveness. OBJECTIVE: To determine the
      scope and effectiveness of educational practices to improve the detection,
      categorization, and identification of skin lesions. DATA SOURCES: Literature
      indexed in MEDLINE, EMBASE, CINAHL, ERIC, PsycINFO, and BIOSIS Previews from
      inception until April 1, 2014, using terms cognate with skin disease, diagnosis,
      and education. STUDY SELECTION: Studies in which the educational objective was
      operationalized as the ability to detect, categorize, or identify skin lesions,
      and the intervention was evaluated through comparisons of participants' abilities
      before and after the intervention. DATA EXTRACTION AND SYNTHESIS: Information
      about trainees, educational practices, educational outcomes, and study quality
      was extracted; it was synthesized through meta-analysis using a random effects
      model. Effect sizes were calculated by dividing the differences between
      preintervention and postintervention means by the pooled standard deviation (ie,
      standardized mean difference [SMD]). Heterogeneity was assessed using an I2
      statistic. MAIN OUTCOMES AND MEASURES: Pooled effect size across all studies and
      separate effect sizes for each of the educational practices. RESULTS: Thirty
      seven studies reporting 47 outcomes from 7 educational practices met our
      inclusion criteria. The pooled effect of the practices on participants' abilities
      was large, with an SMD of 1.06 (95% CI, 0.81-1.31) indicating that posttest
      scores were approximately 1 SD above pretest scores. Effect sizes varied
      categorically between educational practices: the dermatology elective (SMD =
      1.64; 95% CI, 1.17-2.11) and multicomponent interventions (SMD = 2.07; 95% CI,
      0.71-3.44) had large effects; computer-based learning (SMD = 0.64; 95% CI, 0.36
      0.92), lecture (SMD = 0.59; 95% CI, 0.28-0.90), pamphlet (SMD = 0.47; 95% CI, 
      0.11 to 1.05), and audit and feedback (SMD = 0.58; 95% CI, 0.10-1.07) had
      moderate effects; and moulage had a small effect (SMD = 0.15; 95% CI, -0.26 to
      0.57). CONCLUSIONS AND RELEVANCE: A number of approaches are used to improve
      participants' abilities to diagnose skin lesions; some are more effective than
      others. The most effective approaches engage participants in a number of
      coordinated activities for an extended period, providing learners with the
      breadth of knowledge and practice required to change the mechanisms underlying
      performance.

PMID- 25565126
TI  - The Prognostic Role of Optimal Cytoreduction in Advanced, Bowel Infiltrating
      Ovarian Cancer.
AB  - AIM: In locally advanced ovarian cancer with bowel involvement appropriate
      surgical treatment is still controversial. Objective was to delineate factors to
      select those most likely to benefit from radical surgery in patients with locally
      advanced ovarian cancer. METHODS: Therefore, we retrospectively evaluated 207
      consecutive patients with primary stage IIB-IV ovarian cancer who underwent
      primary surgery between 2000 and 2007. Every patient received stage-related
      surgery and adjuvant platinum-based chemotherapy. Median follow-up was 53.5
      months. Data collected included stage, histology, extent of cytoreduction and
      type of bowel resection. Univariate survival analyses were performed to
      investigate variables associated with outcome. RESULTS: Optimal cytoreduction
      (OCR) (R <= 1 cm) was achieved in 76.8%. Most patients presented histologic grade
      2/3 (96.6%), serous ovarian cancers (84.1%) and lymph node involvement (52.2%).
      Complete cytoreduction (R = 0 mm) has significant best prognostic impact in FIGO
      IIB-IV (p = .026). Regarding bowel involvement, bowel resection was performed in
      82 patients (39.6%). In this subgroup of patients complete cytoreduction led to
      significant better overall survival than R > 0 mm-1 cm, even in FIGO IIIC-IV
      patients (p = .027); this fact is independent of bowel resection. Noticeably, for
      survival bowel resection achieving residual tumor mass below 1 cm was also one
      main prognostic factor and even recurrence rate was associated with residual
      tumor mass. CONCLUSION: Our findings suggest that the major prognostic factor in
      patients with advanced ovarian cancer needing colorectal resection is
      completeness of cytoreduction. Therefore, in advanced ovarian cancer patients,
      multivisceral surgery is indicated to achieve OCR (R <= 1 cm) with or without
      bowel resection with best prognostic impact.

PMID- 25565127
TI  - A paramagnetic heterobimetallic polymer: synthesis, reactivity, and ring-opening
      polymerization of tin-bridged homo- and heteroleptic vanadoarenophanes.
AB  - The synthesis of the first tin-bridged bis(benzene) vanadium and trovacene
      sandwich compounds and the investigation of their oxidative addition and
      insertion behavior are reported. The vanadoarenophanes and the corresponding
      platinum insertion products were fully characterized including electrochemical
      and electron paramagnetic resonance (EPR) measurements. Controllable ring-opening
      polymerization of the heteroleptic tin-bridged [1]trovacenophane using Karstedt's
      catalyst yields a high molecular weight polymer (up to M(n) = 89 200 g.mol(-1))
      composed of d(5)-vanadium metal centers in the main chain, making it a rare
      example of a spin-carrying macromolecule. Magnetic susceptibility measurements
      (SQUID) confirm the paramagnetic scaffold with repeating S = 1/2 centers in the
      main chain and suggest antiferromagnetic interactions between adjacent spin sites
      (Weiss constant Theta = -2.9 K).

PMID- 25565128
TI  - MALDI-TOF MS lipid profiles of cytochrome c oxidases: cardiolipin is not an
      essential component of the Paracoccus denitrificans oxidase.
AB  - Lipids of cytochrome c oxidase (COX) of Paracoccus denitrificans have been
      identified by MALDI-TOF MS direct analyses of isolated protein complexes,
      avoiding steps of lipid extraction or chromatographic separation. Two different
      COX preparations have been considered in this study: the enzyme core consisting
      of subunits I and II (COX 2-SU) and the complete complex comprising all four
      subunits (COX 4-SU). In addition, MALDI-TOF MS lipid profiles of bacterial COX
      are also compared with those of the isolated mitochondrial COX and bacterial bc1
      complex. We show that the main lipids associated with bacterial COX 4-SU are
      phosphatidylglycerol (PG) and phosphatidylcholine (PC), and minor amounts of
      cardiolipin (CL). PG and PC are absent in the COX 2-SU preparation lacking
      subunits III and IV, whereas CL is still present. Quantitative analyses indicate
      that at variance from mitochondrial COX, cardiolipin is present in
      substoichiometric amounts in bacterial COX, at a CL:COX molar ratio of ~1:10. We
      conclude that bacterial COX does not require CL for structure or its activity. 

PMID- 25565129
TI  - Australian and New Zealand Gastroenterology International Training Association
      and Gastro 2015.

PMID- 25565130
TI  - The in vitro immune modulatory effect of bisphenol A on fish macrophages via
      estrogen receptor alpha and nuclear factor-kappaB signaling.
AB  - Bisphenol A (BPA) is a well-known environmental endocrine-disrupting chemical.
      Employing primary macrophages from head kidney of red common carp (Cyprinus
      carpio), the present study aimed to evaluate the immune modulatory effect of BPA
      and to explore its potential action mechanism associated with estrogen receptor
      (ER) and nuclear factor-kappaB (NF-kappaB) pathways. A dynamic response process
      was observed in macrophages upon various concentrations of BPA exposure, which
      significantly enhanced the antibacterial activity of macrophages at 0.1, 1, or 10
      MUg/L, but instead induced the apoptosis at 100, 1000, and 10,000 MUg/L. A
      potential pro-inflammatory effect of BPA exposure was suggested, judging from the
      increased production of nitrite oxide and reactive oxygen species (ROS), the
      induction of interleukin-1beta mRNA and protein, as well as NF-kappaB and other
      NF-kappaB-associated immune gene expression. Following BPA coexposure with the ER
      or NF-kappaB antagonist, the induction of ROS, ERalpha, and NF-kappaB-associated
      immune gene expression was significantly inhibited, implying interaction between
      those two pathways. This study thus indicated that low doses of BPA exposure
      alone could significantly disturb the immune response of fish primary macrophages
      in vitro, and for the first time revealed the synergistic action of ERalpha and
      NF-kappaB transcription factors in the BPA effect.

PMID- 25565132
TI  - The identification of a volume-regulated anion channel: an amazing Odyssey.
AB  - The volume-regulated anion channel (VRAC) plays a pivotal role in cell volume
      regulation in essentially all cell types studied. Additionally, VRAC appears to
      contribute importantly to a wide range of other cellular functions and
      pathological events, including cell motility, cell proliferation, apoptosis and
      excitotoxic glutamate release in stroke. Although biophysically,
      pharmacologically and functionally thoroughly described, VRAC has until very
      recently remained a genetic orphan. The search for the molecular identity of VRAC
      has been long and has yielded multiple potential candidates, all of which
      eventually turned out to have properties not fully compatible with those of VRAC.
      Recently, two groups have independently identified the protein leucine-rich
      repeats containing 8A (LRRC8A), belonging to family of proteins (LRRC8A-E)
      distantly related to pannexins, as the likely pore-forming subunit of VRAC. In
      this brief review, we summarize the history of the discovery of VRAC, outline its
      basic biophysical and pharmacological properties, link these to several cellular
      functions in which VRAC appears to play important roles, and sketch the amazing
      search for the molecular identity of this channel. Finally, we describe
      properties of the LRRC8 proteins, highlight some features of the LRRC8A knockout
      mouse and discuss the impact of the discovery of LRRC8 as VRAC on future
      research. 

PMID- 25565131
TI  - Regenerated soleus muscle shows reduced creatine kinase efflux after contractile
      activity in vitro.
AB  - Regenerated skeletal muscles show less muscle damage after strenuous muscle
      exercise. The aim of the studies was to investigate if the regeneration is
      associated with reduced muscle creatine kinase (CK) efflux immediately after the
      exercise. Cryolesion was applied to the soleus muscle of 3-month-old C57BL/6J
      male mice. Then total CK efflux was assessed in vitro in the regenerated muscles
      without exercise or after 100 eccentric contractions. The same measurements were
      performed in the control muscles, which were not exposed to cryolesion.
      Regenerated muscles generated weaker (P < 0.05) twitches, but stronger (P < 0.05)
      150-Hz and 300-Hz tetani with prolonged (P < 0.01) contraction times compared
      with the control muscles. There was no difference between regenerated and control
      muscles in the total CK efflux without exercise, but only control muscles showed
      an increase (P < 0.001) in the CK efflux after the exercise. Our results suggest
      that muscle regeneration is associated with modulation of contractile properties
      and improvement in muscle resistance to damage after eccentric exercise. 

PMID- 25565133
TI  - Generating patient specific pseudo-CT of the head from MR using atlas-based
      regression.
AB  - Radiotherapy planning and attenuation correction of PET images require simulation
      of radiation transport. The necessary physical properties are typically derived
      from computed tomography (CT) images, but in some cases, including stereotactic
      neurosurgery and combined PET/MR imaging, only magnetic resonance (MR) images are
      available. With these applications in mind, we describe how a realistic, patient
      specific, pseudo-CT of the head can be derived from anatomical MR images. We
      refer to the method as atlas-based regression, because of its similarity to atlas
      based segmentation. Given a target MR and an atlas database comprising MR and CT
      pairs, atlas-based regression works by registering each atlas MR to the target
      MR, applying the resulting displacement fields to the corresponding atlas CTs
      and, finally, fusing the deformed atlas CTs into a single pseudo-CT. We use a
      deformable registration algorithm known as the Morphon and augment it with a
      certainty mask that allows a tailoring of the influence certain regions are
      allowed to have on the registration. Moreover, we propose a novel method of
      fusion, wherein the collection of deformed CTs is iteratively registered to their
      joint mean and find that the resulting mean CT becomes more similar to the target
      CT. However, the voxelwise median provided even better results; at least as good
      as earlier work that required special MR imaging techniques. This makes atlas
      based regression a good candidate for clinical use.

PMID- 25565134
TI  - Mediating Community Participation: Practice of Support Workers in Initiating,
      Facilitating or Disrupting Encounters between People with and without
      Intellectual Disability.
AB  - Promoting community participation for people with intellectual disability through
      encounter with strangers is an integral part of the mission of disability support
      workers. This paper offers detailed micro-level analysis of the practices of
      support workers when they accompany a person with intellectual disability outside
      their home and explores the subtle differences which make some staff practices
      more effective than others in promoting more convivial encounters with strangers.
      Based on 160 h of observations of twenty-six adults with intellectual disability
      in a variety of public places, and interviews and focus groups with their support
      workers, the paper points to some of the critical judgements support workers need
      to make when considering whether, when and how to initiate or intervene in such
      encounters. 

PMID- 25565135
TI  - Paralytic toxin profile of the marine dinoflagellate Gymnodinium catenatum Graham
      from the Mexican Pacific as revealed by LC-MS/MS.
AB  - The paralytic shellfish toxin (PST) profiles of Gymnodinium catenatum Graham have
      been reported for several strains from the Pacific coast of Mexico cultured under
      different laboratory conditions, as well as from natural populations. Up to 15
      saxitoxin analogues occurred and the quantity of each toxin depended on the
      growth phase and culture conditions. Previous analysis of toxin profiles of G.
      catenatum isolated from Mexico have been based on post-column oxidation liquid
      chromatography with fluorescence detection (LC-FLD), a method prone to artefacts
      and non-specificity, leading to misinterpretation of toxin composition. We
      describe, for the first time, the complete toxin profile for several G. catenatum
      strains from diverse locations of the Pacific coast of Mexico. The new results
      confirmed previous reports on the dominance of the less potent sulfocarbamoyl
      toxins (C1/2); significant differences, however, in the composition (e.g.,
      absence of saxitoxin, gonyautoxin 2/3 and neosaxitoxin) were revealed in our
      confirmatory analysis. The LC-MS/MS analyses also indicated at least seven
      putative benzoyl toxin analogues and provided support for their existence. This
      new toxin profile shows a high similarity (> 80%) to the profiles reported from
      several regions around the world, suggesting low genetic variability among global
      populations. 

PMID- 25565136
TI  - Non-random expression of ribosomal DNA units in a grasshopper showing high
      intragenomic variation for the ITS2 region.
AB  - We analyse intragenomic variation of the ITS2 internal transcribed spacer of
      ribosomal DNA (rDNA) in the grasshopper Eyprepocnemis plorans, by means of tagged
      PCR 454 amplicon sequencing performed on both genomic DNA (gDNA) and RNA-derived
      complementary DNA (cDNA), using part of the ITS2 flanking coding regions (5.8S
      and 28S rDNA) as an internal control for sequencing errors. Six different ITS2
      haplotypes (i.e. variants for at least one nucleotide in the complete ITS2
      sequence) were found in a single population, one of them (Hap4) being specific to
      a supernumerary (B) chromosome. The analysis of both gDNA and cDNA from the same
      individuals provided an estimate of the expression efficiency of the different
      haplotypes. We found random expression (i.e. about similar recovery in gDNA and
      cDNA) for three haplotypes (Hap1, Hap2 and Hap5), but significant underexpression
      for three others (Hap3, Hap4 and Hap6). Hap4 was the most extremely
      underexpressed and, remarkably, it showed the lowest sequence conservation for
      the flanking 5.8-28S coding regions in the gDNA reads but the highest
      conservation (100%) in the cDNA ones, suggesting the preferential expression of
      mutation-free rDNA units carrying this ITS2 haplotype. These results indicate
      that the ITS2 region of rDNA is far from complete homogenization in this species,
      and that the different rDNA units are not expressed at random, with some of them
      being severely downregulated. 

PMID- 25565138
TI  - The application of LbL-microcarriers for the treatment of chronic inflammation:
      monitoring the impact of LbL-microcarriers on cell viability.
AB  - Layer-by-Layer (LbL) coated microcarriers provide a multifunctional drug delivery
      system for therapeutic substances into specific cells. Inflammatory cells as
      polymorphonuclear leukocytes (PMNs) represent a particularly promising target for
      LbL-microcarriers transporting anti-inflammatory substances such as alpha1 
      antitrypsin (AT). They facilitate a local, low-dose and time-controlled
      application of the assembled therapeutic to effectively inhibit destructive
      enzymes provided by PMNs. But besides therapeutic effects, microcarriers
      themselves are not expected to affect cell viability. Thus, the present study
      emphasizes the investigation of LbL-microcarriers regarding their necrotic or
      apoptotic influence on inflammatory cells. The detection of mitochondrial
      membrane potential changes, reporting the induction of cellular apoptosis, was
      completed by the detection of apoptotic changes of the nucleus and lactate
      dehydrogenase release reporting potential necrotic influences. Investigations of
      microcarrier interactions with HL-60 cells and blood-isolated PMNs show very low
      influence on necrosis and, in case of AT-functionalized microcarriers, even a
      prolonged maintenance of mitochondrial membrane potential underlining the high
      potential of LbL-microcarriers. 

PMID- 25565137
TI  - MicroRNA-215 Regulates Fibroblast Function: Insights from a Human Fibrotic
      Disease.
AB  - MicroRNAs are implicated in the regulation of gene expression via various
      mechanisms in health and disease, including fibrotic processes. Pterygium is an
      ocular surface condition characterized by abnormal fibroblast proliferation and
      matrix deposition. We aimed to investigate the role of microRNAs in pterygium and
      understand the relevant cellular and molecular mechanisms. To achieve this
      objective, a combination of approaches using surgically excised paired human
      pterygium and conjunctival tissues as well as cultured primary fibroblast cells
      from tissue explants were evaluated. Fibroblast dysfunction has been shown to
      play a central role in pterygium pathology. Here we show that miR-215, among a
      few others, was down-regulated (2-fold) in pterygium compared to control, and
      this was consistent in microarray, real-time PCR and fluorescent in-situ
      hybridization. The effects of increased miR-215 were investigated by adding
      exogenous miR-215 to fibroblasts, and this showed a decrease in cell
      proliferation but no significant apoptosis compared to control. Further cell
      cycle analysis showed that miR-215 depressed progression of cells at G1/S as well
      as G2/M. A few cell cycle related transcripts were downregulated (2.2-4.5-fold)
      on addition of miR-215: Mcm3, Dicer1, Cdc25A, Ick, Trip13 and Mcm10. Theoretic
      binding energies were used to predict miR-215 binding targets and luciferase
      reporter studies confirmed Mcm10 and Cdc25A as direct targets. In summary, mir
      215 could play a role in inhibiting fibroblast proliferation in ocular surface
      conjunctiva. Dampening of this mir-215 could result in increased fibroblast cell
      cycling and proliferation, with possibly increased fibroblastic production of
      matrix, inducing pterygium formation. 

PMID- 25565139
TI  - In vitro evaluation of the acquisition of resistance, antifungal activity and
      synergism of Brazilian red propolis with antifungal drugs on Candida spp.
AB  - AIMS: To evaluate the ability of Candida parapsilosis and Candida glabrata to
      develop phenotypic resistance to a benzophenone enriched fraction obtained from
      Brazilian red propolis (BZP-BRP) as compared to fluconazole (FLC). To investigate
      possible synergy between BZP-BRP and FLC and anidulafungin (AND). METHODS AND
      RESULTS: To analyse the development of resistance, isolates susceptible to these
      antifungals were cultured in increasing concentrations of FLC and BZP-BRP. The
      increase in FLC minimum inhibitory concentration for all isolates was evident and
      the majority developed resistance, whereas none isolated became less susceptible
      to BZP-BRP. Synergism was investigated by checkerboard method. BZP-BRP
      demonstrated synergy with FLC and indifference with AND for most isolates.
      CONCLUSIONS: In conclusion, the synergism observed with FLC suggests that BZP-BRP
      could be a possible therapeutic strategy for the treatment of infections related
      to FLC-resistant Candida sp. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      indiscriminate use of antifungals results in the emergence of drug-resistant
      strains among previously susceptible populations. BZP-BRP can become an
      alternative for the treatment of persistent infections caused by Candida sp.

PMID- 25565140
TI  - Construction of a fuzzy and Boolean logic gates based on DNA.
AB  - Logic gates are devices that can perform logical operations by transforming a set
      of inputs into a predictable single detectable output. The hybridization
      properties, structure, and function of nucleic acids can be used to make DNA
      based logic gates. These devices are important modules in molecular computing and
      biosensing. The ideal logic gate system should provide a wide selection of
      logical operations, and be integrable in multiple copies into more complex
      structures. Here we show the successful construction of a small DNA-based logic
      gate complex that produces fluorescent outputs corresponding to the operation of
      the six Boolean logic gates AND, NAND, OR, NOR, XOR, and XNOR. The logic gate
      complex is shown to work also when implemented in a three-dimensional DNA origami
      box structure, where it controlled the position of the lid in a closed or open
      position. Implementation of multiple microRNA sensitive DNA locks on one DNA
      origami box structure enabled fuzzy logical operation that allows biosensing of
      complex molecular signals. Integrating logic gates with DNA origami systems opens
      a vast avenue to applications in the fields of nanomedicine for diagnostics and
      therapeutics. 

PMID- 25565141
TI  - Contrasting effects of land use intensity and exotic host plants on the
      specialization of interactions in plant-herbivore networks.
AB  - Human land use tends to decrease the diversity of native plant species and
      facilitate the invasion and establishment of exotic ones. Such changes in land
      use and plant community composition usually have negative impacts on the
      assemblages of native herbivorous insects. Highly specialized herbivores are
      expected to be especially sensitive to land use intensification and the presence
      of exotic plant species because they are neither capable of consuming alternative
      plant species of the native flora nor exotic plant species. Therefore, higher
      levels of land use intensity might reduce the proportion of highly specialized
      herbivores, which ultimately would lead to changes in the specialization of
      interactions in plant-herbivore networks. This study investigates the community
      wide effects of land use intensity on the degree of specialization of 72 plant
      herbivore networks, including effects mediated by the increase in the proportion
      of exotic plant species. Contrary to our expectation, the net effect of land use
      intensity on network specialization was positive. However, this positive effect
      of land use intensity was partially canceled by an opposite effect of the
      proportion of exotic plant species on network specialization. When we analyzed
      networks composed exclusively of endophagous herbivores separately from those
      composed exclusively of exophagous herbivores, we found that only endophages
      showed a consistent change in network specialization at higher land use levels.
      Altogether, these results indicate that land use intensity is an important
      ecological driver of network specialization, by way of reducing the local host
      range of herbivore guilds with highly specialized feeding habits. However,
      because the effect of land use intensity is offset by an opposite effect owing to
      the proportion of exotic host species, the net effect of land use in a given
      herbivore assemblage will likely depend on the extent of the replacement of
      native host species with exotic ones. 

PMID- 25565142
TI  - Epigenetic regulation of the lncRNA MEG3 and its target c-MET in pancreatic
      neuroendocrine tumors.
AB  - Biallelic inactivation of MEN1 encoding menin in pancreatic neuroendocrine tumors
      (PNETs) associated with the multiple endocrine neoplasia type 1 (MEN1) syndrome
      is well established, but how menin loss/inactivation initiates tumorigenesis is
      not well understood. We show that menin activates the long noncoding RNA
      maternally expressed gene 3 (Meg3) by histone-H3 lysine-4 trimethylation and CpG
      hypomethylation at the Meg3 promoter CRE site, to allow binding of the
      transcription factor cAMP response element-binding protein. We found that Meg3
      has tumor-suppressor activity in PNET cells because the overexpression of Meg3 in
      MIN6 cells (insulin-secreting mouse PNET cell line) blocked cell proliferation
      and delayed cell cycle progression. Gene expression microarray analysis showed
      that Meg3 overexpression in MIN6 mouse insulinoma cells down-regulated the
      expression of the protooncogene c-Met (hepatocyte growth factor receptor), and
      these cells showed significantly reduced cell migration/invasion. Compared with
      normal islets, mouse or human MEN1-associated PNETs expressed less MEG3 and more
      c-MET. Therefore, a tumor-suppressor long noncoding RNA (MEG3) and suppressed
      protooncogene (c-MET) combination could elicit menin's tumor-suppressor activity.
      Interestingly, MEG3 and c-MET expression was also altered in human sporadic
      insulinomas (insulin secreting PNETs) with hypermethylation at the MEG3 promoter
      CRE-site coinciding with reduced MEG3 expression. These data provide insights
      into the beta-cell proliferation mechanisms that could retain their functional
      status. Furthermore, in MIN6 mouse insulinoma cells, DNA-demethylating drugs
      blocked cell proliferation and activated Meg3 expression. Our data suggest that
      the epigenetic activation of lncRNA MEG3 and/or inactivation of c-MET could be
      therapeutic for treating PNETs and insulinomas. 

PMID- 25565143
TI  - Feedforward and feedback control in apraxia of speech: effects of noise masking
      on vowel production.
AB  - PURPOSE: This study was designed to test two hypotheses about apraxia of speech
      (AOS) derived from the Directions Into Velocities of Articulators (DIVA) model
      (Guenther et al., 2006): the feedforward system deficit hypothesis and the
      feedback system deficit hypothesis. METHOD: The authors used noise masking to
      minimize auditory feedback during speech. Six speakers with AOS and aphasia, 4
      with aphasia without AOS, and 2 groups of speakers without impairment (younger
      and older adults) participated. Acoustic measures of vowel contrast, variability,
      and duration were analyzed. RESULTS: Younger, but not older, speakers without
      impairment showed significantly reduced vowel contrast with noise masking.
      Relative to older controls, the AOS group showed longer vowel durations overall
      (regardless of masking condition) and a greater reduction in vowel contrast under
      masking conditions. There were no significant differences in variability. Three
      of the 6 speakers with AOS demonstrated the group pattern. Speakers with aphasia
      without AOS did not differ from controls in contrast, duration, or variability.
      CONCLUSION: The greater reduction in vowel contrast with masking noise for the
      AOS group is consistent with the feedforward system deficit hypothesis but not
      with the feedback system deficit hypothesis; however, effects were small and not
      present in all individual speakers with AOS. Theoretical implications and
      alternative interpretations of these findings are discussed.

PMID- 25565144
TI  - Online breath analysis of propofol during anesthesia: clinical application of
      membrane inlet-ion mobility spectrometry.
AB  - BACKGROUND: Breath analysis of propofol is a potential noninvasive method for
      approximating the plasma propofol concentration. There have been various reported
      techniques for measuring the exhaled propofol concentration at steady state;
      however, the propofol concentration undergoes marked changes during clinical
      anesthesia. Therefore, this study investigated the use of membrane inlet-ion
      mobility spectrometry (MI-IMS) to monitor exhaled propofol discontinuously and
      continuously during propofol anesthesia. METHODS: The study included 19 patients
      of American Society of Anesthesiologists physical status I or II. In experiment I
      (discontinuous study), breath and blood samples were collected discontinuously,
      with stable target propofol concentrations of 2.8 MUg/ml, 3.2 MUg/ml, 3.5 MUg/ml,
      and 3.8 MUg/ml. In experiment II (continuous study), propofol concentration was
      maintained at 3.5 MUg/ml after induction, and exhaled breath was collected
      continuously every 3 min during propofol infusion. Relationships of the exhaled
      propofol concentration with the plasma propofol concentration, measured by high
      performance liquid chromatography and the continuously measured bispectral (BIS)
      index were investigated. RESULTS: Comparison of the exhaled and plasma propofol
      concentrations revealed a bias +/- precision of 2.1% +/- 14.6% (95% limits of
      agreement: - 26.5-30.7%) in experiment I and - 10.4% +/- 13.2 (- 36.3-15.4%) in
      experiment II. In both experiments, exhaled propofol concentrations measured by
      MI-IMS were consistent with, the propofol effect represented by the BIS index.
      CONCLUSIONS: MI-IMS may be a suitable method to predict plasma propofol
      concentration online during propofol anesthesia. Monitoring exhaled propofol may
      improve the safety of propofol anesthesia.

PMID- 25565146
TI  - Ionic bonding of lanthanides, as influenced by d- and f-atomic orbitals, by core
      shells and by relativity.
AB  - Lanthanide trihalide molecules LnX3 (X = F, Cl, Br, I) were quantum chemically
      investigated, in particular detail for Ln = Lu (lutetium). We applied density
      functional theory (DFT) at the nonrelativistic and scalar and SO-coupled
      relativistic levels, and also the ab initio coupled cluster approach. The
      chemically active electron shells of the lanthanide atoms comprise the 5d and 6s
      (and 6p) valence atomic orbitals (AO) and also the filled inner 4f semivalence
      and outer 5p semicore shells. Four different frozen-core approximations for Lu
      were compared: the (1s(2) -4d(10) ) [Pd] medium core, the [Pd+5s(2) 5p(6) = Xe]
      and [Pd+4f(14) ] large cores, and the [Pd+4f(14) +5s(2) 5p(6) ] very large core.
      The errors of Lu?X bonding are more serious on freezing the 5p(6) shell than the
      4f(14) shell, more serious upon core-freezing than on the effective-core
      potential approximation. The Ln?X distances correlate linearly with the AO radii
      of the ionic outer shells, Ln(3+) -5p(6) and X(-) -np(6) , characteristic for
      dominantly ionic Ln(3+) -X(-) binding. The heavier halogen atoms also bind
      covalently with the Ln-5d shell. Scalar relativistic effects contract and
      destabilize the Lu?X bonds, spin orbit coupling hardly affects the geometries but
      the bond energies, owing to SO effects in the free atoms. The relativistic
      changes of bond energy BE, bond length Re , bond force k, and bond stretching
      frequency vs do not follow the simple rules of Badger and Gordy (Re ~BE~k~vs ).
      The so-called degeneracy-driven covalence, meaning strong mixing of accidentally
      near-degenerate, nearly nonoverlapping AOs without BE contribution is critically
      discussed.

PMID- 25565145
TI  - Multidifferentiation potential of human mesenchymal stem cells from adipose
      tissue and hamstring tendons for musculoskeletal cell-based therapy.
AB  - AIM: Adipose-derived stem cells (ASCs) have been deeply characterized for their
      usefulness in musculoskeletal tissue regeneration; recently, other mesenchymal
      stem cell (MSC) sources have also been proposed. This study compares for the
      first time human tendon stem/progenitor cells isolated from hamstring tendons
      with human ASCs. MATERIALS & METHODS: Human TSPCs and ASCs were isolated from
      hamstring tendon portions and adipose tissue of healthy donors undergoing ACL
      reconstruction or liposuction, respectively (n = 7). Clonogenic ability,
      immunophenotype and multi-differentiation potential were assessed and compared.
      RESULTS: Both populations showed similar proliferation and clonogenic ability and
      expressed embryonic stem cell genes and MSC surface markers. Tendon
      stem/progenitor cells showed lower adipogenic and osteogenic ability, but after
      the chondrogenic differentiation, they produced more abundant glycosaminoglycans
      and expressed higher levels of aggrecan with regards to ASCs. The tenogenic
      induction with BMP-12 upregulated SCX and DCN gene expression in both
      populations. CONCLUSION: Our results demonstrate that waste hamstring tendon
      fragments could represent a convenient MSC source for musculoskeletal
      regenerative medicine.

PMID- 25565147
TI  - Inheritance, fitness costs, incomplete resistance and feeding preferences in a
      laboratory-selected MON810-resistant strain of the true armyworm Mythimna
      unipuncta.
AB  - BACKGROUND: The low efficacy of MON810 maize against Mythimna unipuncta
      represents a scenario of non-compliance with the 'high-dose' strategy, raising
      concerns about potential resistance development and outbreaks of this secondary
      pest. The present study offers insight into the different components related to
      resistance in a laboratory-selected MON810-resistant (MR) strain of M. unipuncta.
      RESULTS: The resistance in the MR strain is autosomal and inherited as a
      partially dominant trait. We have found a lack of fitness costs in this strain
      for essential life history traits, reproductive potential and most of the
      population growth parameters analysed, the only exception being an increment in
      the mean generation time. Larvae of the MR strain reared on Bacillus
      thuringiensis (Bt) maize took longer to develop, presented a high adult
      cumulative emergence time and had lower growth rate than those reared on non-Bt
      maize, suggesting the existence of incomplete resistance. Feeding preference
      assays reveal a low discrimination between Bt and conventional maize. CONCLUSION:
      Both resistant and heterozygous larvae of M. unipuncta survive the Cry1Ab toxin
      expressed on Bt maize, with a weak fitness cost for the homozygous larvae,
      indicating the potential risk of field-evolved resistance and its relevance to
      resistance monitoring. (c) 2015 Society of Chemical Industry.

PMID- 25565148
TI  - Identification of polybrominated diphenyl ether metabolites based on calculated
      boiling points from COSMO-RS, experimental retention times, and mass spectral
      fragmentation patterns.
AB  - The COnductor-like Screening MOdel for Realistic Solvents (COSMO-RS) was used to
      predict the boiling points of several polybrominated diphenyl ethers (PBDEs) and
      methylated derivatives (MeO-BDEs) of monohydroxylated BDE (OH-BDE) metabolites.
      The linear correlation obtained by plotting theoretical boiling points calculated
      by COSMO-RS against experimentally determined retention times from gas
      chromatography-mass spectrometry facilitated the identification of PBDEs and OH
      BDEs. This paper demonstrates the applicability of COSMO-RS in identifying
      unknown PBDE metabolites of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and
      2,2',4,4',6-pentabromodiphenyl ether (BDE-100). Metabolites of BDE-47 and BDE-100
      were formed through individual incubations of each PBDE with recombinant
      cytochrome P450 2B6. Using calculated boiling points and characteristic mass
      spectral fragmentation patterns of the MeO-BDE positional isomers, the identities
      of the unknown monohydroxylated metabolites were proposed to be 2'-hydroxy
      2,3',4,4'-tetrabromodiphenyl ether (2'-OH-BDE-66) from BDE-47, and 2'-hydroxy
      2,3',4,4',6-pentabromodiphenyl ether (2'-OH-BDE-119) and 4-hydroxy-2,2',3,4',6
      pentabromodiphenyl ether (4-OH-BDE-91) from BDE-100. The collective use of
      boiling points predicted with COSMO-RS, and characteristic mass spectral
      fragmentation patterns provided a valuable tool toward the identification of
      isobaric compounds. 

PMID- 25565149
TI  - Structural characterization of highly oriented naphthalene-diimide-bithiophene
      copolymer films via vibrational spectroscopy.
AB  - Epitaxially grown highly oriented crystalline films, named form I and form II,
      and spin-coated films of poly{[N,N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8
      bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)}, P(NDI2OD-T2), have
      been investigated through infrared vibrational spectroscopy techniques (infrared
      absorption in double transmission at normal incidence (IRA-TR) and reflection
      absorption infrared spectroscopy at grazing angle incidence (RAIRS)) to get
      access to polymer chain orientation and structure. An analytic model to correlate
      the experimental intensities of the IR bands with structural parameters has been
      developed and applied for the three film morphologies. While spin-coated and form
      I films show P(NDI2OD-T2) chains lying parallel to the substrate in the face-on
      arrangement, form II films feature a structure with chains tilted out from the
      surface. The combined experimental and theoretical methodology gives insights
      into the local molecular orientations of naphthalene diimide (NDI2OD) and
      bithiophene (T2) counits. This approach can be easily extended to a variety of
      organic polymer semiconductors, allowing one to directly correlate molecular
      structure to properties such as charge transport, which is of fundamental
      relevance for developing quantitative models for applications in organic
      electronics and photovoltaics. 

PMID- 25565150
TI  - Fast flux module detection using matroid theory.
AB  - Flux balance analysis (FBA) is one of the most often applied methods on genome
      scale metabolic networks. Although FBA uniquely determines the optimal yield, the
      pathway that achieves this is usually not unique. The analysis of the optimal
      yield flux space has been an open challenge. Flux variability analysis is only
      capturing some properties of the flux space, while elementary mode analysis is
      intractable due to the enormous number of elementary modes. However, it has been
      found by Kelk et al. (2012) that the space of optimal-yield fluxes decomposes
      into flux modules. These decompositions allow a much easier but still
      comprehensive analysis of the optimal-yield flux space. Using the mathematical
      definition of module introduced by Muller and Bockmayr (2013b), we discovered
      useful connections to matroid theory, through which efficient algorithms enable
      us to compute the decomposition into modules in a few seconds for genome-scale
      networks. Using that every module can be represented by one reaction that
      represents its function, in this article, we also present a method that uses this
      decomposition to visualize the interplay of modules. We expect the new method to
      replace flux variability analysis in the pipelines for metabolic networks.

PMID- 25565152
TI  - Notch in memories: Points to remember.
AB  - Memory is a temporally evolving molecular and structural process, which involves
      changes from local synapses to complex neural networks. There is increasing
      evidence for an involvement of developmental pathways in regulating synaptic
      communication in the adult nervous system. Notch signaling has been implicated in
      memory formation in a variety of species. Nevertheless, the mechanism of Notch
      underlying memory consolidation remains poorly understood. In this commentary,
      besides offering an overview of the advances in the field of Notch in memory, we
      highlight some of the weaknesses of the studies and attempt to cast light on the
      apparent discrepancies on the role of Notch in memory. We believe that future
      studies, employing high-throughput technologies and targeted Notch loss and gain
      of function animal models, will reveal the mechanisms of Notch dependent
      plasticity and resolve whether this signaling pathway is implicated in the
      cognitive deficit associated with dementia.

PMID- 25565153
TI  - The effects of acute aerobic exercise on the primary motor cortex.
AB  - The effect of aerobic exercise on primary motor cortical excitability is a
      relevant area of interest for both motor learning and motor rehabilitation.
      Transient excitability changes that may follow an exercise session are a
      necessary precursor to more lasting neuroplastic changes. While the number of
      studies is limited, research suggests that a session of aerobic exercise can
      create an ideal environment for the early induction of plasticity. Potential
      mechanisms include the upregulation of neurotransmitter activity, altered
      cerebral metabolism and cortisol levels, and increases in brain-derived
      neurotrophic factor. While there is considerable evidence that chronic physical
      activity positively impacts brain health and function, studies examining cortical
      excitability changes and motor performance after a single session of exercise are
      lacking. Further research is required to determine the clinical utility and
      feasibility of aerobic exercise. 

PMID- 25565154
TI  - Are the UK courts clamping down on 'evergreening' strategies for the extension of
      patent protection?

PMID- 25565151
TI  - Impact of patient and navigator race and language concordance on care after
      cancer screening abnormalities.
AB  - BACKGROUND: Patient navigation improves the timely diagnosis of cancer among
      minorities, but little is known about the effects of patient and navigator race
      and language concordance on health outcomes. METHODS: The authors investigated
      the effects of patient and navigator race and language concordance on the time to
      diagnosis of cancer screening abnormalities among participants in the Boston
      Patient Navigation Research Program, a clinical effectiveness trial for women who
      had breast or cervical cancer screening abnormalities identified from January 1,
      2007 to December 31, 2008. Hazard ratios and 95% confidence intervals were
      estimated using proportional hazards regression adjusting for clinical and
      demographic factors. RESULTS: In total, 1257 women had breast cancer screening
      abnormalities (n = 655) or cervical cancer screening abnormalities (n = 602)
      identified, and 56% were nonwhite. Language concordance was associated with
      timelier resolution for all patients in the cervical cancer screening
      abnormalities group during the first 90 days (adjusted hazard ratio, 1.46; 95%
      confidence interval, 1.18-1.80), and specifically for Spanish speakers during the
      first 90 days (adjusted hazard ratio, 1.43; 95% confidence interval, 1.10-1.84),
      but no difference was observed after 90 days for women who had cervical cancer
      screening abnormalities or at any time for those who had breast cancer screening
      abnormalities. Race concordance was associated with significant decreases in the
      time to diagnosis for minority women with breast and cervical cancer screening
      abnormalities in analyses stratified by race, but no differences were observed in
      analyses that included all women. CONCLUSIONS: Patient navigator race and
      language concordance improved the timeliness of care in a minority population.
      Patient navigators who are racially/ethnically diverse and multilingual may help
      address barriers to care and improve cancer outcomes for low-income minorities.

PMID- 25565157
TI  - ENaC inhibitors for the treatment of cystic fibrosis.
AB  - The epithelial Na(+) channel, ENaC, is a key regulator of the volume of airway
      surface liquid in the human airway epithelium. In cystic fibrosis (CF), Na(+)
      hyperabsorption through ENaC in the absence of CFTR-mediated anion secretion
      results in the dehydration of respiratory secretions and the impairment of
      mucociliary clearance. The hypothesis of utilizing an ENaC-blocking molecule to
      facilitate restoration of the airway surface liquid volume sufficiently to allow
      normal mucociliary clearance is of interest in the management of lung disease in
      CF patients. This article summarizes the published patent applications from 2010
      that claim approaches to inhibit the function of ENaC for utility in the
      treatment of CF. Patents were located though SciFinder((r)), using "ENaC" as the
      keyword from 2010 onwards; documents not relevant to CF were then manually
      removed. 

PMID- 25565158
TI  - Oral insulin-delivery system for diabetes mellitus.
AB  - Current insulin therapy for diabetes mellitus involves frequent dosing of
      subcutaneous injections, causing local discomfort, patient noncompliance,
      hypoglycemia and hyperinsulinemia, among others. While noninvasive therapy
      through oral delivery is greatly desired, there are challenges that include low
      bioavailability due to rapid enzymatic degradation in the stomach, inactivation
      and digestion by proteolytic enzymes in the intestinal lumen, poor permeability
      across the intestinal epithelium and poor stability. This article reviews patents
      that provide novel approaches for oral insulin delivery to the bloodstream
      through the GI tract. 

PMID- 25565159
TI  - A comprehensive review of patented antileishmanial agents.
AB  - On 14 October 2010, the WHO reported that more than 1 billion people worldwide
      who live in remote rural areas are affected by neglected tropical diseases.
      Leishmaniasis is caused by protozoa of more than 20 different species in humans.
      The three major forms of disease are cutaneous, mucocutaneous and visceral
      leishmaniasis (VL). Cutaneous leishmaniasis causes an ulcer on exposed parts of
      the body and it was estimated that 0.7-1.3 million cases occur worldwide
      annually. Mucocutaneous leishmaniasis leads to destruction of mucous membranes in
      various parts of the body and it was reported that it occurs widely in South
      America. VL is a deadly disease and it is characterized by various symptoms, such
      as anemia, fever, fatigue and weight loss. The WHO estimated that 200,000-400,000
      cases per annum of VL occur worldwide. Although different drugs and drug
      combinations are used for leishmaniasis, US FDA-approved drugs are limited.
      Miltefosine is the only drug approved for all forms of leishmaniasis and
      AmBisome((r)) is approved for VL. Moreover, the drugs used for leishmaniasis have
      severe side effects. The article summarizes the patents filed between January
      2010 and June 2013 for antileishmanial activity. The article covers only the
      chemical agents and excludes the vaccines and the peptides. A large number of
      compounds are filed for antileishmanial activity annually, but only a few are
      more potent than reference drugs such as miltefosine, pentamidine and
      metronidazole. In addition, most of the compounds are not as efficient as
      amphotericin B. Therefore, there is a need for novel compounds that are not only
      potent than the FDA-approved AmBisome and miltefosine, but are also less toxic
      and more cost effective in humans. This article provides an eclectic compilation
      of different classes of compounds that are active against amastigotes (the
      protozoa form found in humans) for the treatment of leishmaniasis. 

PMID- 25565161
TI  - Fragmentation of tetrahydrofuran molecules by H(+), C(+), and O(+) collisions at
      the incident energy range of 25-1000 eV.
AB  - We have studied fragmentation processes of the gas-phase tetrahydrofuran (THF)
      molecules in collisions with the H(+), C(+), and O(+) cations. The collision
      energies have been varied between 25 and 1000 eV and thus covered a velocity
      range from 10 to 440 km/s. The following excited neutral fragments of THF have
      been observed: the atomic hydrogen H(n), n = 4-9, carbon atoms in the 2p3s (1)P1,
      2p4p (1)D2, and 2p4p (3)P states and vibrationally and rotationally excited
      diatomic CH fragments in the A(2)Delta and B(2)Sigma(-) states. Fragmentation
      yields of these excited fragments have been measured as functions of the
      projectile energy (velocity). Our results show that the fragmentation mechanism
      depends on the projectile cations and is dominated by electron transfer from
      tetrahydrofuran molecules to cations. It has been additionally hypothesized that
      in the C(+)+THF collisions a [C-C4H8O](+) complex is formed prior to
      dissociation. The possible reaction channels involved in fragmentation of THF
      under the H(+), C(+), and O(+) cations impact are also discussed. 

PMID- 25565162
TI  - Expanding the substrate scope of chitooligosaccharide oxidase from Fusarium
      graminearum by structure-inspired mutagenesis.
AB  - Chitooligosaccharide oxidase from Fusarium graminearum (ChitO) oxidizes N-acetyl
      D-glucosamine (GlcNAc) and its oligomers with high efficiency at the C1-hydroxyl
      moiety while it shows poor or no activity with other carbohydrates. By sequence
      and structural comparison with other known carbohydrate oxidases
      (glucooligosaccharide oxidase from Acremonium strictum and lactose oxidase from
      Microdochium nivale) eleven mutants were designed to redirect the catalytic scope
      of ChitO for improved oxidation of lactose, cellobiose and maltose. The catalytic
      properties of the most interesting mutants were further improved by combining
      single mutations. This has resulted in the creation of a set of ChitO variants
      that display totally different substrate tolerances. One ChitO variant shows a
      dramatic improvement in catalytic efficiency towards oxidation of glucose,
      cellobiose, lactose, and maltose. We also describe a ChitO variant with the
      highest catalytic efficiency in GlcNAc oxidation so far reported in the
      literature.

PMID- 25565160
TI  - Adenosine effects on inhibitory synaptic transmission and excitation-inhibition
      balance in the rat neocortex.
AB  - KEY POINTS: Adenosine might be the most widespread neuromodulator in the brain,
      but its effects on inhibitory transmission in the neocortex are not understood.
      Here we report that adenosine suppresses inhibitory transmission to layer 2/3
      pyramidal neurons via activation of presynaptic A1 receptors. We present evidence
      for functional A2A receptors, which have a weak modulatory effect on the A1
      mediated suppression, at about 50% of inhibitory synapses at pyramidal neurons.
      Adenosine suppresses excitatory and inhibitory transmission to a different
      extent, and can change the excitation-inhibition balance at a set of synapses
      bidirectionally, but on average the balance was maintained during application of
      adenosine. These results suggest that changes of adenosine concentration may lead
      to differential modulation of excitatory-inhibitory balance in pyramidal neurons,
      and thus redistribution of local spotlights of activity in neocortical circuits,
      while preserving the balanced state of the whole network. ABSTRACT: Adenosine
      might be the most widespread neuromodulator in the brain: as a metabolite of ATP
      it is present in every neuron and glial cell. However, how adenosine affects
      operation of neurons and networks in the neocortex is poorly understood, mostly
      because modulation of inhibitory transmission by adenosine has been so little
      studied. To clarify adenosine's role at inhibitory synapses, and in excitation
      inhibition balance in pyramidal neurons, we recorded pharmacologically isolated
      inhibitory responses, compound excitatory-inhibitory responses and spontaneous
      events in layer 2/3 pyramidal neurons in slices from rat visual cortex. We show
      that adenosine (1-150 MUm) suppresses inhibitory transmission to these neurons in
      a concentration-dependent and reversible manner. The suppression was mediated by
      presynaptic A1 receptors (A1Rs) because it was blocked by a selective A1
      antagonist, DPCPX, and associated with changes of release indices: paired-pulse
      ratio, inverse coefficient of variation and frequency of miniature events. At
      some synapses (12 out of 24) we found evidence for A2ARs: their blockade led to a
      small but significant increase of the magnitude of adenosine-mediated
      suppression. This effect of A2AR blockade was not observed when A1Rs were
      blocked, suggesting that A2ARs do not have their own effect on transmission, but
      can modulate the A1R-mediated suppression. At both excitatory and inhibitory
      synapses, the magnitude of A1R-mediated suppression and A2AR-A1R interaction
      expressed high variability, suggesting high heterogeneity of synapses in the
      sensitivity to adenosine. Adenosine could change the balance between excitation
      and inhibition at a set of inputs to a neuron bidirectionally, towards excitation
      or towards inhibition. On average, however, these bidirectional changes cancelled
      each other, and the overall balance of excitation and inhibition was maintained
      during application of adenosine. These results suggest that changes of adenosine
      concentration may lead to differential modulation of excitatory-inhibitory
      balance in pyramidal neurons, and thus redistribution of local spotlights of
      activity in neocortical circuits, while preserving the balanced state of the
      whole network.

PMID- 25565163
TI  - Excited-state multiple proton transfer depending on the acidity and basicity of
      mediating alcohols in 7-azaindole-(ROH)2 (R = H, CH3) complexes: a theoretical
      study.
AB  - Long-range proton transfer plays an important role in many chemical and
      biological phenomena. It has recently been reported that the rate of excited
      state multiple proton transfer depends on the acidity and basicity of mediating
      alcohols in the H-bonded wire. The excited-state triple proton transfer in 7
      azaindole complexes through cyclic H-bonded wires was theoretically studied to
      investigate rates depending on the mediating alcohols. This study showed that the
      acidity and basicity of alcohols collectively functioned to assist proton
      transfers depending on the paths; the proton transfers of protolytic and
      solvolytic paths were assisted by the pull-behind effect and the push-ahead
      effect, respectively. Both proton-donating and accepting abilities of alcohols in
      the H-bonded wire can accumulate to help proton transfer, and the strong acidity
      and basicity of the alcohols with relatively small structural changes in the wire
      have larger impacts on reducing the activation energies than those of alcohols
      that trigger proton transfer. 

PMID- 25565164
TI  - A retrospective analysis of severe intraoperative respiratory compliance changes
      during ophthalmic arterial chemosurgery for retinoblastoma.
AB  - BACKGROUND AND OBJECTIVES: Ophthalmic arterial chemosurgery for retinoblastoma
      has been associated with intraoperative decreases in respiratory compliance.
      Through the analysis of data from computerized records, we objectively defined
      severe respiratory compliance events and correlated them with demographic and
      clinical information in patients undergoing this procedure. METHODS: Data were
      collected from ophthalmic arterial chemosurgery cases from 2006 to 2013.
      Intraoperative PIP, PEEP, TV, SpO2 , and EtCO2 were analyzed. Compliance changes,
      desaturations, decreases in EtCO2 , and clinical outcomes were assessed. RESULTS:
      Respiratory compliance decreases with a bimodal distribution. Severe events were
      defined as exhibiting a minimum compliance decrease of 40%. Seventy-eight of 122
      children (64%) experienced a severe compliance event during at least one
      treatment, and it occurred in 137/468 cases (29%). A subset of 94 children had
      complete or at least the first three records. The incidence of a severe
      respiratory compliance event in this subgroup was 17/94 (18%) on the first and
      84/261 (32%) on subsequent procedures. The probability of developing a severe
      respiratory compliance event on a subsequent procedure was 0.40 if the child
      developed it on the first procedure, 0.30 if he did not; this difference was not
      significant. The incidence of desaturation below 90% with severe respiratory
      compliance events was 0.20; the incidence of a 30% drop in EtCO2 was 0.34. No
      morbidity, no extended recovery, and no admissions were associated with
      intraoperative severe respiratory compliance events. We found no correlation
      between history, age, sex, weight or allergies, and intraoperative severe
      respiratory compliance events. CONCLUSIONS: Here, most patients experienced a
      severe respiratory compliance event during at least one of their procedures.
      Overall incidence was 29% and was more likely on subsequent procedures. A severe
      respiratory compliance event at the initial procedure was poorly predictive of
      its occurrence on subsequent procedures. No morbidity was associated with
      intraoperative severe respiratory compliance events.

PMID- 25565165
TI  - A modified surgical flap for root coverage in association with grafting
      materials.
AB  - PURPOSE: To clinically evaluate in humans the effectiveness of a modified flap
      for root coverage associated with connective tissue graft or acellular dermal
      matrix graft after a postoperative period of 12 months. MATERIALS AND METHODS:
      Thirty bilateral gingival recessions were selected and randomly assigned into
      experimental groups. All of them were treated with a modified surgical flap, with
      the releasing incisions placed on the mesial and distal line angles of the
      adjacent teeth, distant from the main defect, providing a broader flap. One site
      was treated with the autograft and the contralateral site, with the allograft.
      Probing depth, clinical attachment level, gingival recession, and keratinized
      tissue width were measured at baseline and after 12 months. RESULTS: Both
      procedures significantly improved the clinical parameters evaluated, without
      statistically significant differences between them. While the autograft group had
      a mean gingival recession reduction from 3.15 to 0.67 mm, in the allograft group,
      it was from 3.47 to 0.93 mm. CONCLUSION: The extended flap technique can improve
      the root coverage results using the subepithelial connective tissue graft or the
      acellular dermal matrix. CLINICAL SIGNIFICANCE: Graft survival plays a decisive
      role in mucogingival therapy results and the selection of the appropriate
      surgical technique is important to achieve it. This 12-month randomized study
      showed that an extended flap is able to improve the results of root coverage of
      localized gingival recessions not only when using the acellular dermal matrix as
      shown in a previous study, but also when using the subepithelial connective
      tissue. On this basis, this surgical technique can be suggested as the procedure
      of choice for treating this type of defect.

PMID- 25565166
TI  - The association between serum ApoE genetic polymorphism and serum lipid level in
      hemodialysis patients.
AB  - Growing evidence indicates that apolipoprotein E (ApoE) is one of the most
      important candidate genes for influencing the development of hemodialysis (HD).
      This study aims to detect the potential association between serum ApoE genetic
      polymorphism and serum lipid level in HD. A total of 485 subjects were enrolled
      in this case-control study. The created restriction site polymerase chain
      reaction and DNA sequencing methods were used to investigate ApoE c.109G>A
      genetic polymorphism. Our data suggested that there were significant differences
      in the distribution of allelic and genotypic frequencies between HD patients and
      healthy controls. The levels of total cholesterol, triglyceride, high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, ApoA-I, ApoB, ApoE,
      and lipoprotein (a) for genotype AA were different from genotype GG in HD
      patients and healthy controls. Our findings support that the ApoE c.109G>A
      genetic polymorphism might influence the development of HD and could be a risk
      factor for assessing HD. 

PMID- 25565167
TI  - MCP2013 - 8th International Conference on Multiple Comparison Procedures.

PMID- 25565173
TI  - Metabolic phenotyping of atherosclerotic plaques reveals latent associations
      between free cholesterol and ceramide metabolism in atherogenesis.
AB  - Current optimum medical treatments have had limited success in the primary
      prevention of cardiovascular events, underscoring the need for new pharmaceutical
      targets and enhanced understanding of mechanistic metabolic dysregulation. Here,
      we use a combination of novel metabolic profiling methodologies, based on ultra
      performance liquid chromatography coupled to mass spectrometry (UPLC-MS) followed
      by chemometric modeling, data integration, and pathway mapping, to create a
      systems-level metabolic atlas of atherogenesis. We apply this workflow to compare
      arterial tissue incorporating plaque lesions to intimal thickening tissue
      (immediate preplaque stage). We find changes in several metabolite species
      consistent with well-established pathways in atherosclerosis, such as the
      cholesterol, purine, pyrimidine, and ceramide pathways. We then illustrate
      differential levels of previously unassociated lipids to atherogenesis, namely,
      phosphatidylethanolamine-ceramides (t-test p-values: 3.8 * 10(-6) to 9.8 * 10(
      12)). Most importantly, these molecules appear to be interfacing two pathways
      recognized for their involvement in atherosclerosis: ceramide and cholesterol.
      Furthermore, we show that beta-oxidation intermediates (i.e., acylcarnitines)
      manifest a pattern indicating truncation of the process and overall dysregulation
      of fatty acid metabolism and mitochondrial dysfunction. We develop a metabolic
      framework that offers the ability to map significant statistical associations
      between detected biomarkers. These dysregulated molecules and consequent pathway
      modulations may provide novel targets for pharmacotherapeutic intervention. 

PMID- 25565174
TI  - Contribution of recombination to the evolutionary history of HIV.
AB  - PURPOSE OF REVIEW: An improved understanding of how recombination affects the
      evolutionary history of HIV is crucial to understand its current and future
      evolution. The present review aims to disentangle the manifold effects of
      recombination on HIV by discussing its effects on the evolutionary history and
      the adaptive potential of HIV in the context of concepts from evolutionary
      genetics and genomics. RECENT FINDINGS: The increasing occurrence of secondary
      contacts between divergent subtype populations (during coinfection) results in
      increased observations of recombinants worldwide. Recombination is heterogeneous
      along the HIV genome. Consequences of recombination of HIV evolution are, in
      combination with other demographic processes, expected to either homogenize the
      genetic composition of HIV populations (homogenization) or provide the potential
      for novel adaptations (diversification). New methods in population genomics allow
      deep characterization of recombinant genome (the segment composition and origin)
      and their evolutionary trajectories. SUMMARY: HIV recombinants increase worldwide
      and invade geographical regions where pure subtypes were previously predominant.
      This trend is expected to continue in the future, as ease to travel worldwide
      increases opportunities for recombination between divergent HIV strains. While
      the effects of recombination in HIV are much researched, more effort is required
      to characterize current HIV recombinant composition and dynamics. This can be
      achieved with new population genetic and genomic methods.

PMID- 25565172
TI  - Biodiversity hot spot on a hot spot: novel extremophile diversity in Hawaiian
      fumaroles.
AB  - Fumaroles (steam vents) are the most common, yet least understood, microbial
      habitat in terrestrial geothermal settings. Long believed too extreme for life,
      recent advances in sample collection and DNA extraction methods have found that
      fumarole deposits and subsurface waters harbor a considerable diversity of viable
      microbes. In this study, we applied culture-independent molecular methods to
      explore fumarole deposit microbial assemblages in 15 different fumaroles in four
      geographic locations on the Big Island of Hawai'i. Just over half of the vents
      yielded sufficient high-quality DNA for the construction of 16S ribosomal RNA
      gene sequence clone libraries. The bacterial clone libraries contained sequences
      belonging to 11 recognized bacterial divisions and seven other division-level
      phylogenetic groups. Archaeal sequences were less numerous, but similarly
      diverse. The taxonomic composition among fumarole deposits was highly
      heterogeneous. Phylogenetic analysis found cloned fumarole sequences were related
      to microbes identified from a broad array of globally distributed ecotypes,
      including hot springs, terrestrial soils, and industrial waste sites. Our results
      suggest that fumarole deposits function as an "extremophile collector" and may be
      a hot spot of novel extremophile biodiversity.

PMID- 25565176
TI  - HIV-1 RNAs: sense and antisense, large mRNAs and small siRNAs and miRNAs.
AB  - PURPOSE OF REVIEW: This review summarizes recent findings concerning the ever
      growing HIV-1 RNA population. RECENT FINDINGS: The retrovirus HIV-1 has an RNA
      genome that is converted into DNA and is integrated into the genome of the
      infected host cell. Transcription from the long terminal repeat-encoded promoter
      results in the production of a full-length genomic RNA and multiple spliced
      mRNAs. Recent experiments, mainly based on next-generation sequencing, provided
      evidence for several additional HIV-encoded RNAs, including antisense RNAs and
      virus-encoded microRNAs. SUMMARY: We will survey recent findings related to HIV-1
      RNA biosynthesis, especially regulatory mechanisms that control initiation of
      transcription, capping and polyadenylation. We zoom in on the diversity of HIV-1
      derived RNA transcripts, their mode of synthesis and proposed functions in the
      infected cell. Special attention is paid to the viral transacting responsive RNA
      hairpin motif that has been suggested to encode microRNAs.

PMID- 25565175
TI  - Perspectives on pharmacogenomics of antiretroviral medications and HIV-associated
      comorbidities.
AB  - PURPOSE OF REVIEW: To summarize current knowledge and provide perspective on
      relationships between human genetic variants, antiretroviral medications, and
      aging-related complications of HIV-1 infection. RECENT FINDINGS: Human genetic
      variants have been convincingly associated with interindividual variability in
      antiretroviral toxicities, drug disposition, and aging-associated complications
      in HIV-1 infection. Screening for HLA-B5701 to avoid abacavir hypersensitivity
      reactions has become a routine part of clinical care, and has markedly improved
      drug safety. There are well established pharmacogenetic associations with other
      agents (efavirenz, nevirapine, atazanavir, dolutegravir, and others), but this
      knowledge has yet to have substantial impact on HIV-1 clinical care. As metabolic
      complications including diabetes mellitus, dyslipidemia, osteoporosis, and
      cardiovascular disease are becoming an increasing concern among individuals who
      are aging with well controlled HIV-1 infection, human genetic variants that
      predispose to these complications also become more relevant in this population.
      SUMMARY: Pharmacogenetic knowledge has already had considerable impact on
      antiretroviral prescribing. With continued advances in the field of human
      genomics, the impact of pharmacogenomics on HIV-1 clinical care and research is
      likely to continue to grow in importance and scope.

PMID- 25565177
TI  - Dynamic models of viral replication and latency.
AB  - PURPOSE OF REVIEW: HIV targets primary CD4(+) T cells. The virus depends on the
      physiological state of its target cells for efficient replication, and, in turn,
      viral infection perturbs the cellular state significantly. Identifying the virus
      host interactions that drive these dynamic changes is important for a better
      understanding of viral pathogenesis and persistence. The present review focuses
      on experimental and computational approaches to study the dynamics of viral
      replication and latency. RECENT FINDINGS: It was recently shown that only a
      fraction of the inducible latently infected reservoirs are successfully induced
      upon stimulation in ex-vivo models while additional rounds of stimulation make
      allowance for reactivation of more latently infected cells. This highlights the
      potential role of treatment duration and timing as important factors for
      successful reactivation of latently infected cells. The dynamics of HIV
      productive infection and latency have been investigated using transcriptome and
      proteome data. The cellular activation state has shown to be a major determinant
      of viral reactivation success. Mathematical models of latency have been used to
      explore the dynamics of the latent viral reservoir decay. SUMMARY: Timing is an
      important component of biological interactions. Temporal analyses covering
      aspects of viral life cycle are essential for gathering a comprehensive picture
      of HIV interaction with the host cell and untangling the complexity of latency.
      Understanding the dynamic changes tipping the balance between success and failure
      of HIV particle production might be key to eradicate the viral reservoir.

PMID- 25565178
TI  - Perspectives on electrostatics and conformational motions in enzyme catalysis.
AB  - CONSPECTUS: Enzymes are essential for all living organisms, and their
      effectiveness as chemical catalysts has driven more than a half century of
      research seeking to understand the enormous rate enhancements they provide.
      Nevertheless, a complete understanding of the factors that govern the rate
      enhancements and selectivities of enzymes remains elusive, due to the
      extraordinary complexity and cooperativity that are the hallmarks of these
      biomolecules. We have used a combination of site-directed mutagenesis, pre-steady
      state kinetics, X-ray crystallography, nuclear magnetic resonance (NMR),
      vibrational and fluorescence spectroscopies, resonance energy transfer, and
      computer simulations to study the implications of conformational motions and
      electrostatic interactions on enzyme catalysis in the enzyme dihydrofolate
      reductase (DHFR). We have demonstrated that modest equilibrium conformational
      changes are functionally related to the hydride transfer reaction. Results
      obtained for mutant DHFRs illustrated that reductions in hydride transfer rates
      are correlated with altered conformational motions, and analysis of the
      evolutionary history of DHFR indicated that mutations appear to have occurred to
      preserve both the hydride transfer rate and the associated conformational
      changes. More recent results suggested that differences in local electrostatic
      environments contribute to finely tuning the substrate pKa in the initial
      protonation step. Using a combination of primary and solvent kinetic isotope
      effects, we demonstrated that the reaction mechanism is consistent across a broad
      pH range, and computer simulations suggested that deprotonation of the active
      site Tyr100 may play a crucial role in substrate protonation at high pH. Site
      specific incorporation of vibrational thiocyanate probes into the ecDHFR active
      site provided an experimental tool for interrogating these microenvironments and
      for investigating changes in electrostatics along the DHFR catalytic cycle.
      Complementary molecular dynamics simulations in conjunction with mixed quantum
      mechanical/molecular mechanical calculations accurately reproduced the
      vibrational frequency shifts in these probes and provided atomic-level insight
      into the residues influencing these changes. Our findings indicate that
      conformational and electrostatic changes are intimately related and functionally
      essential. This approach can be readily extended to the study of other enzyme
      systems to identify more general trends in the relationship between
      conformational fluctuations and electrostatic interactions. These results are
      relevant to researchers seeking to design novel enzymes as well as those seeking
      to develop therapeutic agents that function as enzyme inhibitors.

PMID- 25565179
TI  - Associations between long-term exposure to chemical constituents of fine
      particulate matter (PM2.5) and mortality in Medicare enrollees in the eastern
      United States.
AB  - BACKGROUND: Several epidemiological studies have reported that long-term exposure
      to fine particulate matter (PM2.5) is associated with higher mortality. Evidence
      regarding contributions of PM2.5 constituents is inconclusive. OBJECTIVES: We
      assembled a data set of 12.5 million Medicare enrollees (>= 65 years of age) to
      determine which PM2.5 constituents are a) associated with mortality controlling
      for previous-year PM2.5 total mass (main effect); and b) elevated in locations
      exhibiting stronger associations between previous-year PM2.5 and mortality
      (effect modification). METHODS: For 518 PM2.5 monitoring locations (eastern
      United States, 2000-2006), we calculated monthly mortality rates, monthly long
      term (previous 1-year average) PM2.5, and 7-year averages (2000-2006) of major
      PM2.5 constituents [elemental carbon (EC), organic carbon matter (OCM), sulfate
      (SO42-), silicon (Si), nitrate (NO3-), and sodium (Na)] and community-level
      variables. We applied a Bayesian hierarchical model to estimate location-specific
      mortality rates associated with previous-year PM2.5 (model level 1) and identify
      constituents that contributed to the spatial variability of mortality, and
      constituents that modified associations between previous-year PM2.5 and mortality
      (model level 2), controlling for community-level confounders. RESULTS: One
      standard deviation (SD) increases in 7-year average EC, Si, and NO3-
      concentrations were associated with 1.3% [95% posterior interval (PI): 0.3, 2.2],
      1.4% (95% PI: 0.6, 2.4), and 1.2% (95% PI: 0.4, 2.1) increases in monthly
      mortality, controlling for previous-year PM2.5. Associations between previous
      year PM2.5 and mortality were stronger in combination with 1-SD increases in SO42
      and Na. CONCLUSIONS: Long-term exposures to PM2.5 and several constituents were
      associated with mortality in the elderly population of the eastern United States.
      Moreover, some constituents increased the association between long-term exposure
      to PM2.5 and mortality. These results provide new evidence that chemical
      composition can partly explain the differential toxicity of PM2.5.

PMID- 25565180
TI  - Molecular detection of Rickettsia aeschlimannii in Hyalomma spp. ticks from
      camels (Camelus dromedarius) in Nigeria, West Africa.
AB  - Several species of the spotted fever group rickettsiae have been identified as
      emerging pathogens throughout the world, including in Africa. In this study, 197
      Hyalomma ticks (Ixodida: Ixodidae) collected from 51 camels (Camelus dromedarius)
      in Kano, northern Nigeria, were screened by amplification and sequencing of the
      citrate synthase (gltA), outer membrane protein A (ompA) and 17-kDa antigen gene
      fragments. Rickettsia sp. gltA fragments were detected in 43.3% (42/97) of the
      tick pools tested. Rickettsial ompA gene fragments (189 bp and 630 bp) were
      detected in 64.3% (n = 27) and 23.8% (n = 10) of the gltA-positive tick pools by
      real-time and conventional polymerase chain reaction (PCR), respectively. The
      amplicons were 99-100% identical to Rickettsia aeschlimannii TR/Orkun-H and R.
      aeschlimannii strain EgyRickHimp-El-Arish in GenBank. Furthermore, 17-kDa antigen
      gene fragments of 214 bp and 265 bp were detected in 59.5% (n = 25) and 38.1% (n
      = 16), respectively, of tick pools, and sequences were identical to one another
      and 99-100% identical to those of the R. aeschlimannii strain Ibadan A1 in
      GenBank. None of the Hyalomma impressum ticks collected were positive for
      Rickettsia sp. DNA. Rickettsia sp. gltA fragments (133 bp) were detected in 18.8%
      of camel blood samples, but all samples were negative for the other genes
      targeted. This is the first report to describe the molecular detection of R.
      aeschlimannii in Hyalomma spp. ticks from camels in Nigeria.

PMID- 25565181
TI  - General method for the preparation of active esters by palladium-catalyzed
      alkoxycarbonylation of aryl bromides.
AB  - A useful method was developed for the synthesis of active esters by palladium
      catalyzed alkoxycarbonylation of (hetero)aromatic bromides. The protocol was
      general for a range of oxygen nucleophiles including N-hydroxysuccinimide (NHS),
      pentafluorophenol (PFP), hexafluoroisopropyl alcohol (HFP), 4-nitrophenol, and N
      hydroxyphthalimide. A high functional group tolerance was displayed, and several
      active esters were prepared with good to excellent isolated yields. The protocol
      was extended to access an important synthetic precursor to the HIV-protease
      inhibitor, saquinavir, by formation of an NHS ester followed by acyl
      substitution. 

PMID- 25565183
TI  - Usefulness of three-dimensional transesophageal echocardiography in retrieval of
      a dislodged vascular plug used to close paraprosthetic mitral regurgitation.
AB  - In this report, we describe a case of periprocedural dislodgement of an Amplatzer
      Vascular Plug II device during percutaneous closure of severe paraprosthetic
      mitral regurgitation. The free plug in the left atrium was successfully retrieved
      percutaneously using a snare inserted through a sheath under live/real time three
      dimensional transesophageal echocardiographic guidance. This proved crucial not
      only in guiding device deployment but also in detecting and helping management of
      complications. 

PMID- 25565184
TI  - Two different presentations of sinus of valsalva aneurysm.

PMID- 25565185
TI  - Reply: To PMID 24661120.

PMID- 25565187
TI  - High efficiency and optical anisotropy in double-heterojunction nanorod light
      emitting diodes.
AB  - Recent advances in colloidal quantum dot light-emitting diodes (QD-LEDs) have led
      to efficiencies and brightness that rival the best organic LEDs. Nearly ideal
      internal quantum efficiency being achieved leaves light outcoupling as the only
      remaining means to improve external quantum efficiency (EQE) but that might
      require radically different device design and reoptimization. However, the
      current state-of-the-art QD-LEDs are based on spherical core/shell QDs, and the
      effects of shape and optical anisotropy remain essentially unexplored. Here, we
      demonstrate solution-processed, red-emitting double-heterojunction nanorod (DHNR)
      LEDs with efficient hole transport exhibiting low threshold voltage and high
      brightness (76,000 cd m(-2)) and efficiencies (EQE = 12%, current efficiency =
      27.5 cd A(-1), and power efficiency = 34.6 lm W(-1)). EQE exceeding the expected
      upper limit of ~ 8% (based on ~ 20% light outcoupling and solution
      photoluminescence quantum yield of ~ 40%) suggests shape anisotropy and
      directional band offsets designed into DHNRs play an important role in enhancing
      light outcoupling.

PMID- 25565188
TI  - Simplified electrochemically mediated atom transfer radical polymerization using
      a sacrificial anode.
AB  - Simplification of electrochemically mediated atom transfer radical polymerization
      was achieved efficiently under either potentiostatic or galvanostatic conditions
      using an aluminum wire sacrificial anode (seATRP) immersed directly into the
      reaction flask without separating the counter electrode. seATRP polymerizations
      were carried out under different applied potentials, Eapps = E1/2, Epc, Epc -40
      mV, and Epc -80 mV. As the rate of polymerization (Rp) can be modulated by
      applying different Eapp potentials, more reducing conditions resulted in faster
      Rp. The polymerization results showed similar narrow molecular-weight
      distribution throughout the reactions, similar to results observed for n-butyl
      acrylate (BA) polymerization under conventional eATRP. High-molecular-weight PBA
      and diblock copolymers were synthesized by seATRP with more than 90% monomer
      conversion. Furthermore, galvanostatic conditions were developed for synthesizing
      PBA with the two-electrode system.

PMID- 25565189
TI  - Diabetic nephropathy research in China: Data analysis and review from the
      National Natural Science Foundation of China.
AB  - As the largest funding agency of natural science of China, the National Natural
      Science Foundation of China (NSFC) has made great efforts in promoting the
      development of diabetic nephropathy (DN) research in recent years. The aim of the
      current study is to summarize the diabetic nephropathy research in China by
      analyzing NSFC-funded projects. Data on all projects in the DN field funded by
      NSFC from 1986 to 2013 were collected. The funding tendency, funding areas, and
      hotspots in the DN field, and major research institutions, were analyzed. As one
      output of this support, outstanding research groups in China, and their
      representative studies, are also highlighted. From 1986 to 2013, the NSFC has
      funded a total of 248 projects in the DN field, with a total funding amount of
      91.5 million RMB (US$14.9 million). A rapid increase could be seen in the past 5
      years, with an average annual 30% increase in projects numbers and a 52% increase
      in funding amount. All fields in DN research have been covered by the NSFC,
      including etiology, pathophysiology, diagnostics, and therapeutics. Along with
      increased funding of the DN research, there has been a growth in the papers
      published in Science Citation Index journals by Chinese scholars. In the past
      decade, the funding scale and funding budget have increased dramatically.
      Benefiting from this, DN research in China has also made considerable
      progression.

PMID- 25565190
TI  - Hybrids of copolymers of fluorene and C60 -carrying-carbazole with semiconducting
      single-walled carbon nanotubes.
AB  - Three different copolymers of C60 -carrying-carbazole and fluorene units with
      different copolymer composition ratios were designed and synthesized. On the
      basis of photoluminescence, atomic force microscopy, and Vis-NIR and Raman
      spectroscopic analysis, we found that these copolymers solubilize only
      semiconducting single-walled carbon nanotubes (sem-SWNTs) to form copolymer/sem
      SWNT hybrids, in which energy transfer from the copolymer/C60 moieties to the
      SWNTs was revealed. By comparing two possible hybrid structures with molecular
      mechanics simulations, the greatest stabilization was found when the C60 moieties
      lay on the sem-SWNT surfaces. 

PMID- 25565191
TI  - Stem cells for neonatal lung disease caused by SP-B deficiency?

PMID- 25565192
TI  - Chronic congestive heart failure in infancy and childhood: new aspects of
      diagnosis and treatment.
AB  - Congestive heart failure (CHF) is the inability of the heart to meet the
      metabolic demands of the body. As a disease of the advanced age with a frequency
      of 1-2% of the population it is rare in infancy and childhood. The incidence
      ranges from 2.95 (in all US children's hospitals) to 23.2 (University's Childrens
      Hospital Essen) on 1 000 discharges. Among the diagnostic procedures
      echocardiography is the primary modality of imaging. Tei-index and tissue-Doppler
      are more sensitive parameters for LV-dysfunction. BNP/NT-proBNP are age-dependent
      and can guide the long-term therapy. Treatment in childhood does not differ
      basically from that in adulthood, recommended by several guidelines, but data
      regarding the various substances - outlined in detail - are very limited. Here a
      big work has to be done in future! 

PMID- 25565194
TI  - Modifications in integrin expression and extracellular matrix composition in
      children with biliary atresia.
AB  - BACKGROUND: The aetiology of biliary atresia (BA) is still unresolved. The
      study's aim was to investigate the distribution of extracellular matrix proteins
      and cellular adhesion molecules in children with BA compared to other cholestatic
      liver disease (CLD) and normal liver architecture (NLA). PATIENTS: Liver biopsies
      were obtained from children with BA (n=13), CLD (n=6) and NLA (n=8). METHOD: We
      systematically analysed ultra thin frozen sections from the liver hilum stained
      with 25 monoclonal antibodies for cellular characterisation, extracellular matrix
      proteins and adhesion molecules. RESULTS: 2 changes were specifically found in
      BA: laminin beta1 was reduced in children with BA vs. NLA and CLD. Conversely,
      integrin alpha 3 was increased in BA vs. NLA and CLD (p<0.05). Furthermore, we
      detected changes in a similar pattern for both BA and CLD vs. NLA: in BA and CLD
      perlecan was increased. On the contrary, integrin beta1 and entactin were
      decreased vs. NLA (p<0.05). DISCUSSION: Extracellular matrix proteins and
      adhesion molecules mediate cellular polarity and integrity, development of
      tubular structures, and proliferation. Therefore, our findings can be important
      for the understanding of the genesis of BA. CONCLUSION: The composition of
      extracellular matrix proteins and adhesion molecules in children with BA differs
      from NLA and other CLD in distribution of laminin beta1 and integrin alpha 3,
      which may have implications for genetic, immunologic and environmental
      associations in BA.

PMID- 25565195
TI  - Managing neonatal severe sepsis in Germany: a preliminary survey of current
      practices.
AB  - BACKGROUND: In 2002 and 2007, the American College of Critical Care Medicine
      (ACCCM) provided clinical guidelines for hemodynamic support of pediatric and
      neonatal patients in septic shock. In 2008 and 2013, the Surviving Sepsis
      Campaign (SSC) Guidelines Committee offered up-to-date clinical guidelines for
      the management of severe sepsis and septic shock in adults and in pediatric
      patients. The aim of this study was to assess the standard of care of neonates
      with severe sepsis and septic shock in German neonatal intensive care units
      (NICUs) with regard to variability in management and guideline conformity.
      METHODS: 199 pediatric clinics in Germany were asked to describe their management
      of septic neonates in a telephone survey. The questionnaire that was used for the
      preliminary survey was designed based on the ACCCM and SSC clinical guidelines.
      RESULTS: A total of 90 (45%) surveys were completed and analyzed. Among all
      hospitals, the guidelines most commonly included in current practice patterns
      were obtaining cultures before administering antibiotics (100%), determining
      capillary refill time (99%), and using crystalloids for initial fluid therapy
      (97%). The guidelines least commonly included in current practice were
      determination of ammoniac to rule out inborn errors of metabolism (51%) and the
      use of dopamine as the first choice of hemodynamic support (48%). CONCLUSIONS:
      The management of sepsis, severe sepsis, and septic shock in neonates is not
      always guideline consistent, but quite a number of ACCCM and SSC guidelines were
      included in the current practice pattern.

PMID- 25565193
TI  - Management of hypothermia for perinatal asphyxia in Austria - a survey of current
      practice standards.
AB  - BACKGROUND: Therapeutic hypothermia (HT) has been shown to reduce the risk of
      death or disability and increase the rate of survival free of -disability at 18
      24 months of age in hypoxic-ischemic encephalopathy (HIE). OBJECTIVES: The aim of
      this study was to take a national survey which (a) evaluated the practice of
      therapeutic HT for perinatal asphyxia in Austria, (b) evaluated the current
      clinical management of neonatal HIE and (c) evaluated the need for a national
      perinatal asphyxia and HT registry. METHODS: In January 2013, a questionnaire was
      sent out to the clinical heads of all neonatal level-II and level-III units in
      Austria. RESULTS: We received replies from all 30 level II and level III units in
      Austria (response rate 100%). 19 units (63%) answered that they applied HT, 11
      units (37%) said they transferred patients for cooling to other units, 3 of those
      11 units (27%) said they applied cooling during transport. 25 units (83%) felt
      the necessity to establish a national registry. CONCLUSION: The results of this
      survey show that there is already a high implementation of therapeutic HT in
      Austria, but there remains a need for information, awareness and training.
      Problem areas tend to be in the transport of asphyxiated neonates, brain
      monitoring during cooling and follow-up of affected patients. We believe, that
      the establishment of national guidelines and a national register could increase
      awareness for the importance of therapeutic HT in neonatal HIE, thus improve the
      Austrian management of those infants.

PMID- 25565196
TI  - Adjunctive therapies for treatment of severe respiratory failure in newborns.
AB  - BACKGROUND: Severe respiratory failure of the newborn requires adjunctive
      therapies as application of surfactant, inhalation of nitric oxide (iNO), high
      frequency oscillatory ventilation (HFOV), or extracorporeal membrane oxygenation
      (ECMO). We designed this study to analyze the the usage and effectiveness of
      adjunctive therapies and the mortality of severe respiratory failure. PATIENTS
      AND METHODS: The survey in Germany was done in collaboration with the
      "Erhebungseinheit fur seltene padiatrische Erkrankungen" (ESPED). 397 patients
      within 2 years were included into the study. Effectiveness of each adjunctive
      therapy was judged by the treating physician. RESULTS: The most frequent
      diagnosis was respiratory distress syndrome (RDS) with 36.8%, followed by
      pneumonia sepsis (16.4%), meconium aspiration syndrome (MAS) and congenital
      diaphragmatic hernia (CDH). Surfactant was applied in 77.3% of all cases with a
      reported effectiveness of 71.6%. More than 40% of all patients were treated with
      iNO, which led to an improvement in every second case. HFOV was used in every
      third case with a response rate of about 60%. ECMO was performed on one in 7
      patients and was successful with a survival rate of nearly 80%. The overall
      mortality was 10.3%. 29 patients in total died without ECMO. 10 of them might
      actually have been contraindicated, but 19 cases with a potential benefit from
      ECMO were not transferred for ECMO. CONCLUSION: Our study-data suggests that more
      newborns suffering from respiratory failure should be transferred to centers
      offering ECMO.

PMID- 25565197
TI  - Primary cutaneous cryptococcosis in an eight-year-old immunocompetent child: how
      to treat?
AB  - Here we report on a case of primary cryptococcal skin infection in an
      immunocompetent 8-year-old boy. The infection first manifested itself as a
      subcutaneous abscess around the proximal joint of his right thumb after a minor
      injury from contact with a thorny shrub. After surgical incision and drainage was
      performed, Cryptococcus neoformans var. neoformans was the only pathogen cultured
      from the lesion. An agglutination test for the capsular antigen in serum
      displayed negative results and the immunological work-up revealed no underlying
      immunodeficiency. A "watch and wait" strategy - one without systemic antifungal
      treatment - was adopted and this resulted in uneventful healing. In summary,
      primary cryptococcal skin infections in immunocompetent hosts may be managed
      successfully by surgical treatment in combination with careful clinical follow
      up. This approach may help avoid unnecessary antimicrobial treatments. 

PMID- 25565198
TI  - A practical approach to determine dose metrics for nanomaterials.
AB  - Traditionally, administered mass is used to describe doses of conventional
      chemical substances in toxicity studies. For deriving toxic doses of
      nanomaterials, mass and chemical composition alone may not adequately describe
      the dose, because particles with the same chemical composition can have
      completely different toxic mass doses depending on properties such as particle
      size. Other dose metrics such as particle number, volume, or surface area have
      been suggested, but consensus is lacking. The discussion regarding the most
      adequate dose metric for nanomaterials clearly needs a systematic, unbiased
      approach to determine the most appropriate dose metric for nanomaterials. In the
      present study, the authors propose such an approach and apply it to results from
      in vitro and in vivo experiments with silver and silica nanomaterials. The
      proposed approach is shown to provide a convenient tool to systematically
      investigate and interpret dose metrics of nanomaterials. Recommendations for
      study designs aimed at investigating dose metrics are provided.

PMID- 25565199
TI  - Looking ahead: 2015 and beyond ....
AB  - Cell Metabolism turns ten this year! Birthdays are a great time to celebrate and
      reflect on how quickly time went by and how much has changed in a decade. 

PMID- 25565200
TI  - Dysfunctional families: Clostridium scindens and secondary bile acids inhibit the
      growth of Clostridium difficile.
AB  - C. difficile infection is a deadly disease that is influenced by the microbiome.
      In a recent article in Nature, Buffie et al. (2014) demonstrate that the ability
      of C. scindens to synthesize secondary bile acids is crucial to providing
      resistance to C. difficile infection. 

PMID- 25565201
TI  - Essential role for oxidative phosphorylation in cancer progression.
AB  - Cancers are often affected by derangements in mitochondrial (mt) function, as
      well as mtDNA mutations. In this issue, Tan et al. (2015) demonstrate that only
      mtDNA-depleted cancer cells capable of recovering mtDNA from the host form
      metastasizing cancers in vivo, revealing an essential requirement for oxidative
      phosphorylation in tumor progression. 

PMID- 25565202
TI  - NRG4: an endocrine link between brown adipose tissue and liver.
AB  - Brown adipose tissue (BAT) directly regulates energy homeostasis via uncoupling
      of mitochondrial ATP production and thermogenesis. Wang et al. (2014) now report
      that BAT controls liver lipogenesis via secretion of the growth factor NRG4. 

PMID- 25565203
TI  - Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist.
AB  - Increasing energy expenditure through activation of endogenous brown adipose
      tissue (BAT) is a potential approach to treat obesity and diabetes. The class of
      beta3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity
      has never been demonstrated in humans. Here we determined the ability of 200 mg
      oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a beta3-AR agonist currently
      approved to treat overactive bladder, to stimulate BAT as compared to placebo.
      Mirabegron led to higher BAT metabolic activity as measured via (18)F
      fluorodeoxyglucose ((18)F-FDG) using positron emission tomography (PET) combined
      with computed tomography (CT) in all twelve healthy male subjects (p = 0.001),
      and it increased resting metabolic rate (RMR) by 203 +/- 40 kcal/day (+13%; p =
      0.001). BAT metabolic activity was also a significant predictor of the changes in
      RMR (p = 0.006). Therefore, a beta3-AR agonist can stimulate human BAT
      thermogenesis and may be a promising treatment for metabolic disease. 

PMID- 25565204
TI  - Potassium modulates electrolyte balance and blood pressure through effects on
      distal cell voltage and chloride.
AB  - Dietary potassium deficiency, common in modern diets, raises blood pressure and
      enhances salt sensitivity. Potassium homeostasis requires a molecular switch in
      the distal convoluted tubule (DCT), which fails in familial hyperkalemic
      hypertension (pseudohypoaldosteronism type 2), activating the thiazide-sensitive
      NaCl cotransporter, NCC. Here, we show that dietary potassium deficiency
      activates NCC, even in the setting of high salt intake, thereby causing sodium
      retention and a rise in blood pressure. The effect is dependent on plasma
      potassium, which modulates DCT cell membrane voltage and, in turn, intracellular
      chloride. Low intracellular chloride stimulates WNK kinases to activate NCC,
      limiting potassium losses, even at the expense of increased blood pressure. These
      data show that DCT cells, like adrenal cells, sense potassium via membrane
      voltage. In the DCT, hyperpolarization activates NCC via WNK kinases, whereas in
      the adrenal gland, it inhibits aldosterone secretion. These effects work in
      concert to maintain potassium homeostasis. 

PMID- 25565205
TI  - Peroxisomal lipid synthesis regulates inflammation by sustaining neutrophil
      membrane phospholipid composition and viability.
AB  - Fatty acid synthase (FAS) is altered in metabolic disorders and cancer.
      Conventional FAS null mice die in utero, so effects of whole-body inhibition of
      lipogenesis following development are unknown. Inducible global knockout of FAS
      (iFASKO) in mice was lethal due to a disrupted intestinal barrier and leukopenia.
      Conditional loss of FAS was associated with the selective suppression of
      granulopoiesis without disrupting granulocytic differentiation. Transplantation
      of iFASKO bone marrow into wild-type mice followed by Cre induction resulted in
      selective neutrophil depletion, but not death. Impaired lipogenesis increased ER
      stress and apoptosis in neutrophils by preferentially decreasing peroxisome
      derived membrane phospholipids containing ether bonds. Inducible global knockout
      of PexRAP, a peroxisomal enzyme required for ether lipid synthesis, also produced
      neutropenia. FAS knockdown in neutrophil-like HL-60 cells caused cell loss that
      was partially rescued by ether lipids. Inhibiting ether lipid synthesis
      selectively constrains neutrophil development, revealing an unrecognized pathway
      in immunometabolism. 

PMID- 25565206
TI  - Pyruvate kinase M2 regulates Hif-1alpha activity and IL-1beta induction and is a
      critical determinant of the warburg effect in LPS-activated macrophages.
AB  - Macrophages activated by the TLR4 agonist LPS undergo dramatic changes in their
      metabolic activity. We here show that LPS induces expression of the key metabolic
      regulator Pyruvate Kinase M2 (PKM2). Activation of PKM2 using two well
      characterized small molecules, DASA-58 and TEPP-46, inhibited LPS-induced Hif
      1alpha and IL-1beta, as well as the expression of a range of other Hif-1alpha
      dependent genes. Activation of PKM2 attenuated an LPS-induced proinflammatory M1
      macrophage phenotype while promoting traits typical of an M2 macrophage. We show
      that LPS-induced PKM2 enters into a complex with Hif-1alpha, which can directly
      bind to the IL-1beta promoter, an event that is inhibited by activation of PKM2.
      Both compounds inhibited LPS-induced glycolytic reprogramming and succinate
      production. Finally, activation of PKM2 by TEPP-46 in vivo inhibited LPS and
      Salmonella typhimurium-induced IL-1beta production, while boosting production of
      IL-10. PKM2 is therefore a critical determinant of macrophage activation by LPS,
      promoting the inflammatory response. 

PMID- 25565207
TI  - Mitochondrial genome acquisition restores respiratory function and tumorigenic
      potential of cancer cells without mitochondrial DNA.
AB  - We report that tumor cells without mitochondrial DNA (mtDNA) show delayed tumor
      growth, and that tumor formation is associated with acquisition of mtDNA from
      host cells. This leads to partial recovery of mitochondrial function in cells
      derived from primary tumors grown from cells without mtDNA and a shorter lag in
      tumor growth. Cell lines from circulating tumor cells showed further recovery of
      mitochondrial respiration and an intermediate lag to tumor growth, while cells
      from lung metastases exhibited full restoration of respiratory function and no
      lag in tumor growth. Stepwise assembly of mitochondrial respiratory
      (super)complexes was correlated with acquisition of respiratory function. Our
      findings indicate horizontal transfer of mtDNA from host cells in the tumor
      microenvironment to tumor cells with compromised respiratory function to re
      establish respiration and tumor-initiating efficacy. These results suggest
      pathophysiological processes for overcoming mtDNA damage and support the notion
      of high plasticity of malignant cells. 

PMID- 25565209
TI  - CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of
      the mitochondrial calcium uniporter.
AB  - Mitochondrial calcium is an important modulator of cellular metabolism. CCDC90A
      was reported to be a regulator of the mitochondrial calcium uniporter (MCU)
      complex, a selective channel that controls mitochondrial calcium uptake, and
      hence was renamed MCUR1. Here we show that suppression of CCDC90A in human
      fibroblasts produces a specific cytochrome c oxidase (COX) assembly defect,
      resulting in decreased mitochondrial membrane potential and reduced mitochondrial
      calcium uptake capacity. Fibroblasts from patients with COX assembly defects due
      to mutations in TACO1 or COX10 also showed reduced mitochondrial membrane
      potential and impaired calcium uptake capacity, both of which were rescued by
      expression of the respective wild-type cDNAs. Deletion of fmp32, a homolog of
      CCDC90A in Saccharomyces cerevisiae, an organism that lacks an MCU, also produces
      a COX deficiency, demonstrating that the function of CCDC90A is evolutionarily
      conserved. We conclude that CCDC90A plays a role in COX assembly and does not
      directly regulate MCU. 

PMID- 25565208
TI  - PINK1 and Parkin control localized translation of respiratory chain component
      mRNAs on mitochondria outer membrane.
AB  - Mitochondria play essential roles in many aspects of biology, and their
      dysfunction has been linked to diverse diseases. Central to mitochondrial
      function is oxidative phosphorylation (OXPHOS), accomplished by respiratory chain
      complexes (RCCs) encoded by nuclear and mitochondrial genomes. How RCC biogenesis
      is regulated in metazoans is poorly understood. Here we show that Parkinson's
      disease (PD)-associated genes PINK1 and Parkin direct localized translation of
      certain nuclear-encoded RCC (nRCC) mRNAs. Translationally repressed nRCC mRNAs
      are localized in a PINK1/Tom20-dependent manner to mitochondrial outer membrane,
      where they are derepressed and activated by PINK1/Parkin through displacement of
      translation repressors, including Pumilio and Glorund/hnRNP-F, a Parkin
      substrate, and enhanced binding of activators such as eIF4G. Inhibiting the
      translation repressors rescued nRCC mRNA translation and neuromuscular
      degeneration phenotypes of PINK1 mutant, whereas inhibiting eIF4G had opposite
      effects. Our results reveal previously unknown functions of PINK1/Parkin in RNA
      metabolism and suggest new approaches to mitochondrial restoration and disease
      intervention. 

PMID- 25565210
TI  - High-throughput luminescent reporter of insulin secretion for discovering
      regulators of pancreatic Beta-cell function.
AB  - Defects in insulin secretion play a central role in the pathogenesis of type 2
      diabetes, yet the mechanisms driving beta-cell dysfunction remain poorly
      understood, and therapies to preserve glucose-dependent insulin release are
      inadequate. We report a luminescent insulin secretion assay that enables large
      scale investigations of beta-cell function, created by inserting Gaussia
      luciferase into the C-peptide portion of proinsulin. Beta-cell lines expressing
      this construct cosecrete luciferase and insulin in close correlation, under both
      standard conditions or when stressed by cytokines, fatty acids, or ER toxins. We
      adapted the reporter for high-throughput assays and performed a 1,600-compound
      pilot screen, which identified several classes of drugs inhibiting secretion, as
      well as glucose-potentiated secretagogues that were confirmed to have activity in
      primary human islets. Requiring 40-fold less time and expense than the
      traditional ELISA, this assay may accelerate the identification of pathways
      governing insulin secretion and compounds that safely augment beta-cell function
      in diabetes. 

PMID- 25565212
TI  - CYANOCHIP: an antibody microarray for high-taxonomical-resolution cyanobacterial
      monitoring.
AB  - Cyanobacteria are Gram-negative photosynthetic prokaryotes that are widespread on
      Earth. Eutrophication and global warming make some aquatic ecosystems behave as
      bioreactors that trigger rapid and massive cyanobacterial growth with remarkable
      economic and health consequences. Rapid and efficient early warning systems are
      required to support decisions by water body authorities. We have produced 17
      specific antibodies to the most frequent cyanobacterial strains blooming in
      freshwater ecosystems, some of which are toxin producers. A sandwich-type
      antibody microarray immunoassay (CYANOCHIP) was developed for the simultaneous
      testing of any of the 17 strains, or other closely related strains, in field
      samples from different habitats (water, rocks, and sediments). We titrated and
      tested all of the antibodies in succession using a fluorescent sandwich
      microarray immunoassay. Although most showed high specificity, we applied a
      deconvolution method based on graph theory to disentangle the few existing cross
      reactions. The CYANOCHIP sensitivity ranged from 10(2) to 10(4) cells mL(-1),
      with most antibodies detecting approximately 10(2) cells mL(-1). We validated the
      system by testing multiple isolates and crude natural samples from freshwater
      reservoirs and rocks, both in the laboratory and by in situ testing in the field.
      The results demonstrated that CYANOCHIP is a valuable tool for the sensitive and
      reliable detection of cyanobacteria for early warning and research purposes. 

PMID- 25565213
TI  - Contribution of IL-12A and IL-12B polymorphisms to Chlamydia trachomatis-specific
      cell-mediated immune responses.
AB  - Inherited variance in the IL-12B gene is associated with susceptibility to
      Chlamydia trachomatis-induced tubal factor infertility and disease severity. In
      this study, our aim was to discover how polymorphisms in IL-12-coding genes
      influence C. trachomatis-induced immune responses and IL-12 production. The study
      population consisted of 240 women. IL-12A and IL-12B single nucleotide
      polymorphisms (SNPs) were determined from isolated DNA using the Sequenom system
      with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry. We studied lymphocyte proliferative (LP) responses to C.
      trachomatis strains E and F elementary bodies (EBs) and recombinant chlamydial
      heat-shock protein 60 (CHSP60) antigen. IL-12p40 and IL-12p70 levels were
      measured using the BD Flex Set method. We found a statistically significant
      association between the C. trachomatis EB antigen-specific LP response and the
      rs2853694 SNP (P = 0.02). Our study demonstrates that the IL-12 cytokine family
      is involved in C. trachomatis-specific immune responses. Moreover, C. trachomatis
      induced IL-12 production and the IL-12B rs2853694 SNP partially explain
      individual variation in the C. trachomatis LP response. 

PMID- 25565214
TI  - A plasmonic random laser tunable through stretching silver nanowires embedded in
      a flexible substrate.
AB  - A mechanically-tunable random laser based on a waveguide-plasmonic scheme has
      been investigated. This laser can be constructed by spin coating a solution of
      polydimethylsiloxane doped with the rhodamine 6G organic dye and silver nanowires
      onto a silicone rubber slab. The excellent overlap of the plasmon resonance peak
      of the silver nanowires with both the pump wavelength and the photoluminescence
      spectrum provides the low threshold and tuning properties of the random laser.
      The random laser wavelength can be tuned from 558 to 565 nm by stretching the
      soft substrate, which causes reorientation and breakage of the silver nanowires.
      The polarization state of the random laser can also be changed from random
      polarization to partial polarization by stretching. The laser performance remains
      unchanged after the stretching and restoration experiments. These results not
      only enable easy realization of an ultrathin flexible plasmonic random laser but
      also provide insights into the mechanisms of three-dimensional plasmonic feedback
      random lasers. 

PMID- 25565211
TI  - Mouse-human experimental epigenetic analysis unmasks dietary targets and genetic
      liability for diabetic phenotypes.
AB  - Using a functional approach to investigate the epigenetics of type 2 diabetes
      (T2D), we combine three lines of evidence-diet-induced epigenetic dysregulation
      in mouse, epigenetic conservation in humans, and T2D clinical risk evidence-to
      identify genes implicated in T2D pathogenesis through epigenetic mechanisms
      related to obesity. Beginning with dietary manipulation of genetically
      homogeneous mice, we identify differentially DNA-methylated genomic regions. We
      then replicate these results in adipose samples from lean and obese patients pre-
      and post-Roux-en-Y gastric bypass, identifying regions where both the location
      and direction of methylation change are conserved. These regions overlap with 27
      genetic T2D risk loci, only one of which was deemed significant by GWAS alone.
      Functional analysis of genes associated with these regions revealed four genes
      with roles in insulin resistance, demonstrating the potential general utility of
      this approach for complementing conventional human genetic studies by integrating
      cross-species epigenomics and clinical genetic risk. 

PMID- 25565215
TI  - Orbital myositis: a side effect of interferon alpha 2b treatment.

PMID- 25565216
TI  - Camera-based three-dimensional real-time particle tracking at kHz rates and
      Angstrom accuracy.
AB  - Optical and magnetic tweezers are widely employed to probe the mechanics and
      activity of individual biomolecular complexes. They rely on micrometre-sized
      particles to detect molecular conformational changes from the particle position.
      Real-time particle tracking with Angstrom accuracy has so far been only achieved
      using laser detection through photodiodes. Here we demonstrate that camera-based
      imaging can provide a similar performance for all three dimensions. Particle
      imaging at kHz rates is combined, with real-time data processing being
      accelerated by a graphics-processing unit. For particles that are fixed in the
      sample cell we can detect 3-A-sized steps that are introduced by cell
      translations at rates of 10 Hz, while for DNA-tethered particles 5 A steps at 1
      Hz can be resolved. Moreover, 20 particles can be tracked in parallel with
      comparable accuracy. Our approach provides a simple and robust way for high
      resolution tweezer experiments using multiple particles at a time.

PMID- 25565217
TI  - Water-binding phospholipid nanodomains and phase-separated diacylglycerol
      nanodomains regulate enzyme reactions in lipid monolayers.
AB  - Phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) nanodomains
      covered with bound water as well as diacylglycerol 1-palmitoyl-2-oleoyl-sn
      glycerol (POG) nanodomains separated from a lipid membrane were studied, using
      monolayer surfaces of POPC hydrolyzed by phospholipase C (PLC). The investigation
      was based on the analysis of compression isotherms and on atomic force microscope
      (AFM) observations of Langmuir-Blodgett (LB) films and Langmuir-Schaefer (LS)
      films. The results included reaction rate constants obtained by kinetic analysis
      of phosphocholine at surface pressures from 0.1 to 31 mN/m and determined by a
      luminol-enhanced chemiluminescence method. Monolayer elastic modulus values and
      fluorescence microscopic images confirmed that hydrolysis by PLC progressed in
      the intermediate monolayer between a liquid-expanded (L1) film and a liquid
      condensed (L2) film at 2-17 mN/m. Furthermore, the intermediate film was
      confirmed to consist of L1 film and the POPC nanodomains in the L2 state are
      covered with bound water, conclusions based on the following AFM results: (1)
      nanodomains in POPC LS films were catalyzed by PLC, (2) POG nanodomains extended
      out from LB films of mixed POPC/POG 9/1 (mol/mol) monolayers, and (3) POPC LS
      films were covered with bound water, as indicated by cross-sectional analysis. At
      the optimal surface pressure of 10 mN/m, when POPC nanodomains (L2), with
      internal diameters of ~75 nm, were hydrolyzed by PLC, they shrank down into
      pockets of the same size as those that appeared with POG. The resulting pocket
      sizes on LS films were in agreement with POG nanodomain sizes on LB films. This
      study demonstrated that PLC reacted with POPC nanodomains (L2) dispersed in L1/L2
      mixed phase monolayers selectively and that POG nanodomains were phase-separated
      from the monolayer as hydrolysis proceeded. 

PMID- 25565218
TI  - Improved Poly (D,L-lactide) nanoparticles-based formulation for hair follicle
      targeting.
AB  - OBJECTIVE: Hair follicles are widely recognized as the preferential target and
      site of accumulation for nanoparticles after topical application. This feature is
      of particular importance for hair cosmetics, having the potential to refine the
      treatment of several hair follicle-related disorders. The aim of this work was to
      improve the preparation of Poly (D,L-lactide) (PLA) nanoparticles for in vivo
      follicular target and drug delivery. METHODS: Envisaging a future industrial
      scale-up of the process, nanoprecipitation method was used to prepare PLA
      nanoparticles: the effect of several processing parameters on their properties
      was examined and the yield of nanoparticles formation determined. Encapsulation
      efficiencies and in vitro release profiles of lipophilic and hydrophilic model
      compounds were also assessed. In vitro cytotoxicity and ex vivo penetration
      studies were performed on a reference skin cell line (NCTC2455, human skin
      keratinocytes) and porcine skin, respectively. RESULTS: Using acetone : ethanol
      (50 : 50, v/v) as the solvent phase, 0.6% (w/w) of Pluronic((r)) F68 as a
      surfactant agent and agitation to mix the solvent and non-solvent phases, a
      monodispersed population of non-cytotoxic spherical nanoparticles of
      approximately 150 nm was obtained. The yield of nanoparticles for this
      formulation was roughly 90%. After encapsulation of model compounds, no
      significant changes were found in the properties of particles and the entrapment
      efficiencies were above 80%. The release kinetics of dyes from PLA nanoparticles
      indicate an anomalous transport mechanism (diffusion and polymer degradation) for
      Nile Red (lipophilic) and a Fickian diffusion of first order for fluorescein 5(6)
      isothiocyanate (hydrophilic). Ex vivo skin penetration studies confirmed the
      presence of nanoparticles along the entire follicular ducts. CONCLUSIONS: The
      optimized method allows the preparation of ideal PLA nanoparticles-based
      formulations for hair follicle targeting. PLA nanoparticles can effectively
      transport and release lipophilic and hydrophilic compounds into the hair
      follicles, and the yields obtained are acceptable for industrial purposes.

PMID- 25565219
TI  - iPathology cockpit diagnostic station: validation according to College of
      American Pathologists Pathology and Laboratory Quality Center recommendation at
      the Hospital Trust and University of Verona.
AB  - BACKGROUND: Validation of digital whole slide images is crucial to ensure that
      diagnostic performance is at least equivalent to that of glass slides and light
      microscopy. The College of American Pathologists Pathology and Laboratory Quality
      Center recently developed recommendations for internal digital pathology system
      validation. Following these guidelines we sought to validate the performance of a
      digital approach for routine diagnosis by using an iPad and digital control
      widescreen-assisted workstation through a pilot study. METHODS: From January
      2014, 61 histopathological slides were scanned by ScanScope Digital Slides
      Scanner (Aperio, Vista, CA). Two independent pathologists performed diagnosis on
      virtual slides in front of a widescreen by using two computer devices (ImageScope
      viewing software) located to different Health Institutions (AOUI Verona)
      connected by local network and a remote image server using an iPad tablet
      (Aperio, Vista, CA), after uploading the Citrix receiver for iPad. Quality
      indicators related to image characters and work-flow of the e-health cockpit
      enterprise system were scored based on subjective (high vs poor) perception. The
      images were re-evaluated two weeks apart. RESULTS: The whole glass slides
      encountered 10 liver: hepatocarcinoma, 10 renal carcinoma, 10 gastric carcinoma
      and 10 prostate biopsies: adenocarcinoma, 5 excisional skin biopsies: melanoma, 5
      lymph-nodes: lymphoma. 6 immuno- and 5 special stains were available for intra-
      and internet remote viewing. Scan times averaged two minutes and 54 seconds per
      slide (standard deviation 2 minutes 34 seconds). Megabytes ranged from 256 to 680
      (mean 390) per slide storage. Reliance on glass slide, image quality (resolution
      and color fidelity), slide navigation time, simultaneous viewers in
      geographically remote locations were considered of high performance score. Side
      by side comparisons between diagnosis performed on tissue glass slides versus
      widescreen were excellent showing an almost perfect concordance (0.81, kappa
      index). CONCLUSIONS: We validated our institutional digital pathology system for
      routine diagnostic facing with whole slide images in a cockpit enterprise digital
      system or iPad tablet. Computer widescreens are better for diagnosing scanned
      glass slide that iPad. For urgent requests, iPad may be used. Legal aspects have
      to be soon faced with to permit the clinical use of this technology in a manner
      that does not compromise patient care.

PMID- 25565220
TI  - Highly enantioselective [4 + 2] cycloaddition of allenoates and 2-olefinic
      benzofuran-3-ones.
AB  - A highly enantioselective [4 + 2] cycloaddition of allenoates with 2-olefinic
      benzofuran-3-ones catalyzed by (DHQD)2AQN, which allowed the synthesis of
      optically active dihydropyran-fused benzofurans, was developed. 

PMID- 25565221
TI  - Digital immunohistochemistry wizard: image analysis-assisted stereology tool to
      produce reference data set for calibration and quality control.
AB  - BACKGROUND: Digital image analysis (DIA) enables better reproducibility of
      immunohistochemistry (IHC) studies. Nevertheless, accuracy of the DIA methods
      needs to be ensured, demanding production of reference data sets. We have
      reported on methodology to calibrate DIA for Ki67 IHC in breast cancer tissue
      based on reference data obtained by stereology grid count. To produce the
      reference data more efficiently, we propose digital IHC wizard generating initial
      cell marks to be verified by experts. METHODS: Digital images of proliferation
      marker Ki67 IHC from 158 patients (one tissue microarray spot per patient) with
      an invasive ductal carcinoma of the breast were used. Manual data (mD) were
      obtained by marking Ki67-positive and negative tumour cells, using a
      stereological method for 2D object enumeration. DIA was used as an initial step
      in stereology grid count to generate the digital data (dD) marks by Aperio Genie
      and Nuclear algorithms. The dD were collected into XML files from the DIA markup
      images and overlaid on the original spots along with the stereology grid. The
      expert correction of the dD marks resulted in corrected data (cD). The
      percentages of Ki67 positive tumour cells per spot in the mD, dD, and cD sets
      were compared by single linear regression analysis. Efficiency of cD production
      was estimated based on manual editing effort. RESULTS: The percentage of Ki67
      positive tumor cells was in very good agreement in the mD, dD, and cD sets:
      regression of cD from dD (R2=0.92) reflects the impact of the expert editing the
      dD as well as accuracy of the DIA used; regression of the cD from the mD
      (R2=0.94) represents the consistency of the DIA-assisted ground truth (cD) with
      the manual procedure. Nevertheless, the accuracy of detection of individual
      tumour cells was much lower: in average, 18 and 219 marks per spot were edited
      due to the Genie and Nuclear algorithm errors, respectively. The DIA-assisted cD
      production in our experiment saved approximately 2/3 of manual marking.
      CONCLUSIONS: Digital IHC wizard enabled DIA-assisted stereology to produce
      reference data in a consistent and efficient way. It can provide quality control
      measure for appraising accuracy of the DIA steps.

PMID- 25565223
TI  - No need to abandon focused parathyroidectomy: a multicenter study of long-term
      outcome after surgery for primary hyperparathyroidism.
AB  - OBJECTIVE: The aim of this study was to investigate long-term outcomes after
      focused parathyroidectomy (FPTX) and open 4-gland parathyroid exploration (OPTX)
      for primary hyperparathyroidism (pHPT). BACKGROUND: Concerns about increased long
      term recurrence rates after FPTX in conjunction with decreased operative times
      for OPTX have led some groups to abandon FPTX in favor of routine 4-gland
      exploration. METHODS: This is a multicenter retrospective cohort study of
      patients undergoing parathyroidectomy for pHPT from 1990 to 2013. The patient
      cohort was divided into 2 groups, FPTX and OPTX, based on intention-to-treat
      analysis. The primary outcome measure was the persistence of pHPT. Secondary
      outcome measures were differences in the long-term recurrence rate of persisting
      pHPT and surgical complications. RESULTS: A total of 4569 patients (3585 females)
      were included. The overall persistence and recurrence rates were 2.2% and 0.9%,
      respectively, after a median follow-up of 6.5 years. There were 2531 FPTX cases
      and 2038 OPTX cases. The initial persistence rate was higher for FPTX than for
      OPTX (2.7% vs 1.7%, P = 0.036); however, the long-term recurrence rate was not
      different (5-year 0.6% vs 0.4%, log-rank P = 0.08). Complications were more
      common in OPTX than in FPTX (7.6% vs 3.6%, P < 0.001). CONCLUSIONS: FPTX was
      associated with fewer operative complications and an equivalent rate of long-term
      recurrence than with OPTX. Although initial persistence rates were higher after
      FPTX than after OPTX, most were readily resolved with subsequent early
      reoperation. FPTX should not be abandoned in patients with positive preoperative
      localization.

PMID- 25565222
TI  - Natural killer cell subsets in cerebrospinal fluid of patients with multiple
      sclerosis.
AB  - Changes in blood natural killer (NK) cells, important players of the immune
      innate system, have been described in multiple sclerosis (MS). We studied
      percentages and total cell counts of different effector and regulatory NK cells
      in cerebrospinal fluid (CSF) of MS patients and other neurological diseases to
      gain clearer knowledge of the role of these cells in neuroinflammation. NK cell
      subsets were assessed by flow cytometry in CSF of 85 consecutive MS patients (33
      with active disease and 52 with stable MS), 16 with other inflammatory diseases
      of the central nervous system (IND) and 17 with non-inflammatory neurological
      diseases (NIND). MS patients showed a decrease in percentages of different CSF NK
      subpopulations compared to the NIND group. However, absolute cell counts showed a
      significant increase of all NK subsets in MS and IND patients, revealing that the
      decrease in percentages does not reflect a real reduction of these immune cells.
      Remarkably, MS patients showed a significant increase of regulatory/effector
      (CD56(bright) /CD56(dim) ) NK ratio compared to IND and NIND groups. In addition,
      MS activity associated with an expansion of NK T cells. These data show that NK
      cell subsets do not increase uniformly in all inflammatory neurological disease
      and suggest strongly that regulatory CD56(bright) and NK T cells may arise in CSF
      of MS patients as an attempt to counteract the CNS immune activation
      characteristic of the disease. 

PMID- 25565225
TI  - Rhodium-catalyzed borylation of aryl 2-pyridyl ethers through cleavage of the
      carbon-oxygen bond: borylative removal of the directing group.
AB  - The rhodium-catalyzed reaction of aryl 2-pyridyl ethers with a diboron reagent
      results in the formation of arylboronic acid derivatives via activation of the
      C(aryl)-O bonds. The straightforward synthesis of 1,2-disubstituted arenes was
      enabled through catalytic ortho C-H bond functionalization directed by the 2
      pyridyloxy group followed by substitution of this group with a boryl group.
      Several control experiments revealed that the presence of a sp(2) nitrogen atom
      at the 2-position of the substrate and the use of a boron-based reagent were
      crucial for the activation of the relatively inert C(aryl)-O bond of aryl 2
      pyridyl ethers. 

PMID- 25565224
TI  - Cellular basis of secondary infections and impaired desquamation in certain
      inherited ichthyoses.
AB  - IMPORTANCE: Secondary infections and impaired desquamation complicate certain
      inherited ichthyoses, but their cellular basis remains unknown. In healthy human
      epidermis, the antimicrobial peptides cathelicidin (LL-37) and human beta
      defensin 2 (HBD2), as well as the desquamatory protease kallikrein-related
      peptidase 7 (KLK7), are delivered to the stratum corneum (SC) interstices by
      lamellar body (LB) exocytosis. OBJECTIVE: To assess whether abnormalities in the
      LB secretory system could account for increased risk of infections and impaired
      desquamation in inherited ichthyoses with known abnormalities in LB assembly
      (Harlequin ichthyosis [HI]), secretion (epidermolytic ichthyosis [EI]), or
      postsecretory proteolysis (Netherton syndrome [NS]). DESIGN, SETTING, AND
      PARTICIPANTS: Samples from library material were taken from patients with HI, EI,
      NS, and other ichthyoses, but with a normal LB secretory system, and in healthy
      controls and were evaluated by electron microscopy and immunohistochemical
      analysis from July 1, 2010, through March 31, 2013. MAIN OUTCOME AND MEASURES:
      Changes in LB secretion and in the fate of LB-derived enzymes and antimicrobial
      peptides in ichthyotic patients vs healthy controls. RESULTS: In healthy controls
      and patients with X-linked ichthyosis, neutral lipid storage disease with
      ichthyosis, and Gaucher disease, LB secretion is normal, and delivery of LB
      derived proteins and LL-37 immunostaining persists high into the SC. In contrast,
      proteins loaded into nascent LBs and their delivery to the SC interstices
      decrease markedly in patients with HI, paralleled by reduced immunostaining for
      LL-37, HBD2, and KLK7 in the SC. In patients with EI, the cytoskeletal
      abnormality impairs the exocytosis of LB contents and thus results in decreased
      LL-37, HBD2, and KLK7 secretion, causing substantial entombment of these proteins
      within the corneocyte cytosol. Finally, in patients with NS, although abundant
      enzyme proteins loaded in parallel with accelerated LB production, LL-37
      disappears, whereas KLK7 levels increase markedly in the SC. CONCLUSIONS AND
      RELEVANCE: Together, these results suggest that diverse abnormalities in the LB
      secretory system account for the increased risk of secondary infections and
      impaired desquamation in patients with HI, EI, and NS.

PMID- 25565227
TI  - Treatment of migration and extrusion of the gold weight eyelid implant with
      fascia lata sandwich graft technique.
AB  - Gold weight implantation is generally considered a safe procedure for the
      treatment of paralytic lagophthalmos. The most frequently seen complications are
      extrusion, malpositioning, and migration of the implant. To decrease the rate of
      these complications, several modifications were defined in the composition and
      the shape of the implant as well as the surgical technique itself. Despite these
      precautions, implant revision rates are still as high as 8% to 14%. Nowadays,
      implant-covering or implant-wrapping procedures are becoming more popular to
      avoid implant-related problems. However, there is limited information in the
      literature regarding the management of these complications. In this study, we
      aimed to present the treatment of migration and extrusion of the gold weight
      implant in a patient with Moebius syndrome by wrapping the implant with
      autogenous fascia lata graft. 

PMID- 25565226
TI  - Biochemical characterization of a Pseudomonas aeruginosa phospholipase D.
AB  - Phospholipase D is a ubiquitous protein in eukaryotes that hydrolyzes
      phospholipids to generate the signaling lipid phosphatidic acid (PtdOH). PldA, a
      Pseudomonas aeruginosa PLD, is a secreted protein that targets bacterial and
      eukaryotic cells. Here we have characterized the in vitro factors that modulate
      enzymatic activity of PldA, including divalent cations and phosphoinositides. We
      have identified several similarities between the eukaryotic-like PldA and the
      human PLD isoforms, as well as several properties in which the enzymes diverge.
      Notable differences include the substrate preference and transphosphatidylation
      efficiency for PldA. These findings offer new insights into potential regulatory
      mechanisms of PldA and its role in pathogenesis. 

PMID- 25565228
TI  - Chondroid syringoma of the nasal dorsum.
AB  - Chondroid syringoma (CS) is an uncommon cutaneous tumor in the head and neck,
      with reported incidence rate from 0.01% to 0.1%. The CS of skin is a rare type of
      soft tissue tumor originating from the sweat glands. We report a documented case
      of CS occurring in the nasal dorsum in a 58-year-old man, which developed during
      the course of 1 year. The clinical, gross pathologic, and histologic findings of
      the tumor are described. The lesion was totally excised via transcutaneous
      approach and showed no evidence of recurrence after excision. 

PMID- 25565229
TI  - The use of a computed tomographic application for mobile devices in the diagnosis
      of oral and maxillofacial surgery.
AB  - The aim of the current technical report was to introduce a computed tomographic
      (CT) application for mobile devices as a diagnostic tool for analyzing CT images.
      An iPad and an iPhone (Apple, Cuppertino, CA) were used to navigate through
      multiplanar reconstructions of cone beam CT scans, using an application derived
      from the OsiriX CT software. Tools and advantages of this method were recorded.
      In addition, images rendered in the iPad were manipulated during dental implant
      placement and grafting procedures to follow up and confirm the implant digital
      planning in real time. The study population consisted of 10 patients. In all
      cases, it was possible to use image manipulation tools, such as changing contrast
      and brightness, zooming, rotating, panning, performing both linear and area
      measurements, and analyzing gray-scale values of a region of interest.
      Furthermore, it was possible to use the OsiriX application in the dental clinic
      where the study was conducted, to follow-up the analyzed implant placement and
      grafting procedures at the chairside. The current findings suggest that
      technological and practical methods to visualize radiographic images are
      invaluable resources to improve training, teaching, networking, and the
      performance of real-time follow-up of oral and maxillofacial surgical procedures.
      This article discusses the advantages and disadvantages of introducing this new
      technology in the clinical routine. 

PMID- 25565230
TI  - Use of the buccal fat pad as free graft for closure of oronasal fistula in a
      cleft palate patient.
AB  - Oronasal fistulas are frequent complications after cleft lip and palate surgery,
      with difficult treatment because of the presence of fibrotic and scarred tissue
      as well as the absence of local virgin tissue, representing a challenge in oral
      and maxillofacial surgery. The size of the fistula, its location, and the cause
      of the defect are important factors to determine the type of treatment and
      surgical technique. The use of pedicled buccal fat pad (BFP) for the repair of
      cleft palate has shown promising results, becoming a safe and effective method.
      On the other hand, the use of BFP as a free graft for oral defects has been
      rarely described in the literature. The current study is the first case report
      that shows the use of free graft of BFP in oronasal fistula after cleft lip and
      palate surgery and aimed to discuss the promising results of this surgical
      technique, suggesting it as a treatment option for anterior maxillary defects,
      when properly indicated. 

PMID- 25565231
TI  - Modified fixation of acrylic cranioplasty in the setting of titanium allergy.
AB  - Cranioplasty can be performed using a number of materials ranging from autologous
      tissue to metallic or acrylic alloplastic implants. In this report, we present a
      unique case of revision cranioplasty in a patient with titanium allergy using a
      prefabricated, custom-made polymethylmethacrylate implant and a modified fixation
      technique without plates or screws. 

PMID- 25565232
TI  - Dandy-Walker syndrome with severe velopharyngeal dysfunction: a contraindication
      for Le Fort I surgery?
AB  - Dandy-Walker syndrome is a rare congenital brain deformation. Most symptoms are
      related with fourth ventricle and skull base malformations. Quite often, symptoms
      develop from infancy or progress rapidly. Cerebellar dysfunction, lack of muscle
      coordination, and skull deformities involving eye movement might be present.
      There are several Dandy-Walker syndrome complex types. We present a 23-year-old
      patient who had a severe dentofacial deformity with mandibular prognathism and
      extremely undeveloped maxillary bone resulting in palatopharyngeal and
      velopharyngeal dysfunction with complete lack of soft palate function resulting
      in increased speech tone and volume. Performing Le Fort I osteotomy in this case
      is greatly controversial and might result in even greater loss of function or
      even its total lack. Velopharyngeal complex is very important, and every surgeon
      should consider its value while planning Le Fort I osteotomies. 

PMID- 25565233
TI  - Unilateral bone cavities situated near the angle of the mandibula.
AB  - Stafne bone defects (SBDs) are asymptomatic radiolucent lingual/buccal bone
      lesions of the lower jaw and are frequently caused by soft tissue inclusion.
      These defects have a cystlike appearance on plain radiographs. The diagnosis of
      this defect is incidental because patients do not usually present clinical
      symptoms. The common variant of SBD exists at the third molar region of the
      mandible below the inferior alveolar canal. To date, only 1 case of multilocular
      SBD has been reported in the literature, including both clinical cases and
      archaeological specimens. The purpose of the current study was to describe a new
      case of multilocular appearance of SBD near the angle of the mandibula that was
      diagnosed with the aid of a three-dimensional cone beam computed tomographic
      scan. 

PMID- 25565234
TI  - A new surgical technique of rhinophyma (gull-wing technique).
AB  - A variety of surgical techniques have been described for the treatment of
      rhinophyma. A case of severe rhinophyma was operated with a new surgical
      technique. The full-thickness excision was combined with the gull-wing incision
      in this technique. The patient was very satisfied with the result. 

PMID- 25565235
TI  - Video-assisted resection in benign frontal tumors.
AB  - Soft and osseous tumors that develop into the frontal are the most profitable
      with the use of video-assisted surgery, thus avoiding also a visible scar. In the
      Department of Plastic Surgery at Argerich Hospital in Buenos Aires, Argentina,
      from 1999 to 2010, video-assisted operations were used in the treatment of 158
      patients, 26 of them presented lipomas and osteomas into the frontal tissues. In
      all 26 patients, both local anesthesia and incisions behind the hairline were
      performed. Minor complications such as hematoma and transitory paresis of the
      frontal nerve were detected. Video-assisted technique offered both good
      illumination and excellent magnification that not only permits a safe anatomic
      dissection by means of surgical maneuvers in avascular planes but also avoids
      visible scars. The outcome achieved with endoscopic techniques has permitted to
      consider it like the first election in the surgical treatment in tumors developed
      into both soft and osseous tissues of the frontal area, offering more advantages
      than the classic approaches.

PMID- 25565236
TI  - Mandibular lengthening by distraction osteogenesis in the setting of osteogenesis
      imperfecta.
AB  - Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone
      fragility and deformity. The craniofacial skeleton may be involved either
      primarily or by result of a concomitant diagnosis. Distraction osteogenesis has
      emerged as a versatile reconstructive option for many craniofacial deformities.
      Mandibular lengthening by distraction has not been reported in a patient with OI.
      We present a patient in whom mandibular lengthening was successfully performed
      twice for hemifacial microsomia. Bilateral lengthening was initially performed
      with successful airway improvement. This was followed by transport distraction on
      the more severely affected side for condylar reconstruction. Successful
      mandibular lengthening by distraction is possible in the setting of OI. 

PMID- 25565237
TI  - Fixation of fractured inferior orbital wall using fibrin glue in inferior blowout
      fracture surgery.
AB  - The objectives of surgical treatment for orbital fracture are to return soft
      tissue to its original position as well as reduce and fix the bone fragments
      properly. Reduction of the orbital bone through a subciliary or conjunctival
      incision and reduction using a urinary balloon catheter were simultaneously
      performed on 53 patients between 2010 and 2013. Fibrin glue was used to attach
      the reduced bone fragments. These patients had less than 2 cm(2) of bone defect
      and showed diplopia, eye movement limitation, and enophthalmos. Diplopia, eye
      movement limitation, and enophthalmos were each reduced to 3/32, 2/25, and 2/48,
      respectively. There were no adverse effects, such as infection or hematoma, and
      because implants were not used, there was no possibility of its extrusion or
      foreign body reaction. The operation time decreased compared with when using an
      implant, and the bone fragments remained in a fixed position even after removing
      the urinary balloon catheter. Therefore, the use of fibrin glue proved to be
      effective in orbital floor fractures.

PMID- 25565238
TI  - Osteoplastic flap approach versus orbitotomy in case of orbitofrontal cholesterol
      granuloma.
AB  - A 44-year-old man developed a slow-growing painless left superolateral orbital
      mass that extended into the frontal sinus with a complaint of ptosis. Magnetic
      resonance imaging revealed a heterogenous hyperintense lesion confined to the
      left frontal bone and superior orbit. The osteoplastic frontal sinus approach was
      performed to drain supraorbital cholesterol granuloma cyst and for curetting the
      capsule. Orbitofrontal cholesterol granuloma characteristically arises in the
      diploe of the superolateral frontal bone. The traditional approach for a
      primarily orbitofrontal cholesterol granuloma is the transorbital approach
      including anterior orbitotomy or lateral orbitotomy. However, the osteoplastic
      approach should be kept in mind as an alternative aprroach for the management of
      supraorbital lesions in patients with well-pneumatized frontal sinus.

PMID- 25565239
TI  - Sagittal split ramus osteotomy for aneurysmal bone cyst of the mandibular
      condyle.
AB  - Aneurysmal bone cyst is a benign pseudocystic osseous lesion characterized by a
      fibrous connective tissue stroma with cellular fibrous tissue, multinucleated
      giant cells, and large blood-filled spaces with no endothelial lining. The entity
      is uncommon in facial bones, and it rarely involves the mandibular condyle.
      Resection of the lesion is the most accepted treatment. The present case is the
      11th reported case of aneurysmal bone cyst of the mandibular condyle in the
      existing literature and the first where, rather than using conventional extra
      oral approach, sagittal split ramus osteotomy was used to excise the lesion
      successfully with no recurrence after 3 years of follow-up. 

PMID- 25565240
TI  - Simultaneous transsphenoidal and transventricular endoscopic approaches for giant
      pituitary adenoma with hydrocephalus.
AB  - The surgical management of giant pituitary adenomas is challenging. Although most
      pituitary adenomas, even those with suprasellar extension, can be resected using
      the transsphenoidal surgery alone, the transcranial approach is still needed for
      approximately 1% to 4% of these tumors. The transcranial approach is usually used
      in large adenomas with hourglass configuration and adenomas with firm consistency
      impeding the adjunctive measures, which are used for delivering the suprasellar
      part of the tumor into the sellar area and thereby obscure the tumor resection by
      transsphenoidal route. In this report, we describe the successful use of
      transventricular endoscope as an adjunctive measure to remove giant pituitary
      adenoma from transsphenoidal route and discuss the limitations of this new
      technique. We concluded that this technique would be used safely in selected
      cases. Case selection and surgical strategies should be based on preoperative
      magnetic resonance imaging findings, ventricular size, and the availability of
      experienced surgeons.

PMID- 25565241
TI  - Using chemical benchmarking to determine the persistence of chemicals in a
      Swedish lake.
AB  - It is challenging to measure the persistence of chemicals under field conditions.
      In this work, two approaches for measuring persistence in the field were
      compared: the chemical mass balance approach, and a novel chemical benchmarking
      approach. Ten pharmaceuticals, an X-ray contrast agent, and an artificial
      sweetener were studied in a Swedish lake. Acesulfame K was selected as a
      benchmark to quantify persistence using the chemical benchmarking approach. The
      95% confidence intervals of the half-life for transformation in the lake system
      ranged from 780-5700 days for carbamazepine to <1-2 days for ketoprofen. The
      persistence estimates obtained using the benchmarking approach agreed well with
      those from the mass balance approach (1-21% difference), indicating that chemical
      benchmarking can be a valid and useful method to measure the persistence of
      chemicals under field conditions. Compared to the mass balance approach, the
      benchmarking approach partially or completely eliminates the need to quantify
      mass flow of chemicals, so it is particularly advantageous when the
      quantification of mass flow of chemicals is difficult. Furthermore, the
      benchmarking approach allows for ready comparison and ranking of the persistence
      of different chemicals. 

PMID- 25565242
TI  - Incorporating breastfeeding education into prenatal care.
AB  - INTRODUCTION: Prenatal breastfeeding education increases breastfeeding
      initiation, exclusivity, and duration. Current research regarding antenatal
      breastfeeding education suggests that recurrent, individual, and technology-based
      education programs are effective in providing women with evidence-based
      breastfeeding information and guidance. MATERIALS AND METHODS: This project was
      implemented at an obstetrical practice in the northeast United States. Pregnant
      women between 32 weeks of gestation and birth, receiving care from certified
      nurse-midwives, were the targeted population. Three breastfeeding modules were
      created and offered to women at the 32-, 34-, and 36-week prenatal visit via
      computer tablets. Women answered questionnaires at the end of each module,
      serving as a measure for participation and content learning. Women also completed
      a questionnaire at the 6-week postpartum visit to assess summative perceptions.
      RESULTS: Twenty-three women participated, and 21 women completed questionnaires
      at 6 weeks postpartum. All women answered the content questions at the end of the
      modules correctly. Sixty-seven percent reported prior breastfeeding experience,
      95% initiated breastfeeding, 86% were exclusively breastfeeding at 6 weeks
      postpartum, and 71% of the women planned to exclusively breastfeed for 6 months.
      Sixty-seven percent reported the modules promoted or affirmed their decision to
      breastfeed, whereas 5% would have preferred group-based education. Providers
      documented breastfeeding education 52% of the time. CONCLUSIONS: The results of
      this project indicate that women successfully learned breastfeeding content via
      the tablet methodology. The results confirm that prenatal breastfeeding
      education, in the office setting, is well accepted by women. In order to assess
      the impact of the program on breastfeeding success, further study is needed.

PMID- 25565243
TI  - Skeletal muscle satellite cells as myogenic progenitors for muscle homoeostasis,
      growth, regeneration and repair.

PMID- 25565244
TI  - Improving thoracic four-dimensional cone-beam CT reconstruction with anatomical
      adaptive image regularization (AAIR).
AB  - Total-variation (TV) minimization reconstructions can significantly reduce noise
      and streaks in thoracic four-dimensional cone-beam computed tomography (4D CBCT)
      images compared to the Feldkamp-Davis-Kress (FDK) algorithm currently used in
      practice. TV minimization reconstructions are, however, prone to over-smoothing
      anatomical details and are also computationally inefficient. The aim of this
      study is to demonstrate a proof of concept that these disadvantages can be
      overcome by incorporating the general knowledge of the thoracic anatomy via
      anatomy segmentation into the reconstruction. The proposed method, referred as
      the anatomical-adaptive image regularization (AAIR) method, utilizes the adaptive
      steepest-descent projection-onto-convex-sets (ASD-POCS) framework, but introduces
      an additional anatomy segmentation step in every iteration. The anatomy
      segmentation information is implemented in the reconstruction using a heuristic
      approach to adaptively suppress over-smoothing at anatomical structures of
      interest. The performance of AAIR depends on parameters describing the weighting
      of the anatomy segmentation prior and segmentation threshold values. A
      sensitivity study revealed that the reconstruction outcome is not sensitive to
      these parameters as long as they are chosen within a suitable range. AAIR was
      validated using a digital phantom and a patient scan and was compared to FDK, ASD
      POCS and the prior image constrained compressed sensing (PICCS) method. For the
      phantom case, AAIR reconstruction was quantitatively shown to be the most
      accurate as indicated by the mean absolute difference and the structural
      similarity index. For the patient case, AAIR resulted in the highest signal-to
      noise ratio (i.e. the lowest level of noise and streaking) and the highest
      contrast-to-noise ratios for the tumor and the bony anatomy (i.e. the best
      visibility of anatomical details). Overall, AAIR was much less prone to over
      smoothing anatomical details compared to ASD-POCS and did not suffer from
      residual noise/streaking and motion blur migrated from the prior image as in
      PICCS. AAIR was also found to be more computationally efficient than both ASD
      POCS and PICCS, with a reduction in computation time of over 50% compared to ASD
      POCS. The use of anatomy segmentation was, for the first time, demonstrated to
      significantly improve image quality and computational efficiency for thoracic 4D
      CBCT reconstruction. Further developments are required to facilitate AAIR for
      practical use. 

PMID- 25565246
TI  - National trends in the use of postcardiac arrest therapeutic hypothermia and
      hospital factors influencing its use.
AB  - BACKGROUND: Therapeutic hypothermia (TH) in cardiac arrest continues to be
      underused in the United States. A better understanding of its utilization could
      inform future efforts and policies to improve utilization. This study
      investigates trends in TH use for in and out-of-hospital cardiac arrest, and
      hospital factors associated with its use. METHODS: We performed a cross-sectional
      analysis using the Nationwide Inpatient Sample (NIS), 2007-2010, of US adult
      hospitalizations with cardiac arrest. Annual rates of TH use and proportions of
      hospitals using TH were calculated using NIS weighting. Potential hospital
      factors associated with increased likelihood of TH utilization were assessed
      using logistic regression. RESULTS: Across 2007-2010, 1.35% of cardiac arrest
      patients received TH; increasing from 0.34% (2007) to 2.49% (2010). The
      proportion of hospitals using TH was 13.63%, increasing from 4.63% (2007) to
      22.16% (2010). Significant hospital factors associated with TH utilization were:
      large hospitals, urban location, Northeast or West regions, teaching hospitals,
      non-safety net hospitals, increasing year, and hospitals with higher annual
      cardiac arrest volume. CONCLUSION: Utilization of TH in cardiac arrest remains
      low, but increased sevenfold from 2007 to 2010. The significant variability in
      implementation of TH, argues for nationwide best practices or regionalization of
      postcardiac arrest care hospitals.

PMID- 25565248
TI  - Recipient of the 2014 molecular ecology prize: Johanna Schmitt.

PMID- 25565247
TI  - Editorial 2015.

PMID- 25565249
TI  - The influence of the visual modality on language structure and
      conventionalization: insights from sign language and gesture.
AB  - For humans, the ability to communicate and use language is instantiated not only
      in the vocal modality but also in the visual modality. The main examples of this
      are sign languages and (co-speech) gestures. Sign languages, the natural
      languages of Deaf communities, use systematic and conventionalized movements of
      the hands, face, and body for linguistic expression. Co-speech gestures, though
      non-linguistic, are produced in tight semantic and temporal integration with
      speech and constitute an integral part of language together with speech. The
      articles in this issue explore and document how gestures and sign languages are
      similar or different and how communicative expression in the visual modality can
      change from being gestural to grammatical in nature through processes of
      conventionalization. As such, this issue contributes to our understanding of how
      the visual modality shapes language and the emergence of linguistic structure in
      newly developing systems. Studying the relationship between signs and gestures
      provides a new window onto the human ability to recruit multiple levels of
      representation (e.g., categorical, gradient, iconic, abstract) in the service of
      using or creating conventionalized communicative systems. 

PMID- 25565252
TI  - General formation of tin nanoparticles encapsulated in hollow carbon spheres for
      enhanced lithium storage capability.
AB  - A new simple process for synthesis of heterogeneous yolk-shell microspheres is
      introduced. The core/shell-structured microspheres are prepared by a one-pot
      spray pyrolysis process. The removal of one kind of metal oxide by a dry process
      produces heterogeneous yolk-shell microspheres. The yolk-shell Sn@C microspheres
      show superior electrochemical properties as anode materials for lithium-ion
      batteries. 

PMID- 25565250
TI  - Histone methylation patterns in astrocytes are influenced by age following
      ischemia.
AB  - In animal models, middle-aged females sustain greater ischemia-induced infarction
      as compared to adult females. This age difference in infarct severity is
      associated with reduced functional capacity of astrocytes, a critical neural
      support cell. The impaired response of astrocytes following stroke in middle-aged
      females may be related to epigenetic alterations, including histone acetylation
      or methylation. The present study measured the activity of enzymes that regulate
      histone acetylation and methylation in cerebral cortical astrocytes of adult (6
      month) and middle-aged (11+ month) female rats 48 h following middle cerebral
      artery occlusion. H3K4 histone methyltransferase activity was decreased in
      astrocytes from middle-aged females. The next experiment therefore examined
      H3K4me3 (transcriptional enhancer) and H3K9me3 (transcriptional repressor) in
      astrocytes from adult and middle-aged females using ChIP-seq analysis. Adult
      females had more enriched H3K4me3 peaks (304 vs. 26) at transcriptional start
      sites and fewer H3K9me3 enriched peaks than middle-aged females (4 vs. 22),
      indicating a pattern of less active chromatin in astrocytes in the older group
      following ischemia. DAVID clustering analysis of H3K4me3 enriched genes found
      several functional categories, including cell motility, regulation of apoptosis
      and the vascular endothelial growth factor (VEGF) pathway. H3K4me3 was enriched
      at the miR-17-20 cluster and VEGFa, and analysis of a separate set of astrocytes
      confirmed that VEGF protein expression and miR-20 mRNA expression were
      significantly greater following ischemia in adult females compared to middle-aged
      females. These data indicate that astrocytes display less active chromatin with
      aging and provide new insight into possible mechanisms for differences in stroke
      severity observed during aging.

PMID- 25565251
TI  - Community preferences in general practice: important factors for choosing a
      general practitioner.
AB  - BACKGROUND: Understanding the important factors for choosing a general
      practitioner (GP) can inform the provision of consumer information and contribute
      to the design of primary care services. OBJECTIVE: To identify the factors
      considered important when choosing a GP and to explore subgroup differences.
      DESIGN: An online survey asked about the respondent's experience of GP care and
      included 36 questions on characteristics important to the choice of GP.
      PARTICIPANTS: An Australian population sample (n = 2481) of adults aged 16 or
      more. METHODS: Principal components analysis identified dimensions for the
      creation of summated scales, and regression analysis was used to identify patient
      characteristics associated with each scale. RESULTS: The 36 questions were
      combined into five scales (score range 1-5) labelled: care quality, types of
      services, availability, cost and practice characteristics. Care quality was the
      most important factor (mean = 4.4, SD = 0.6) which included questions about
      technical care, interpersonal care and continuity. Cost (including financial and
      time cost) was also important (mean = 4.1, SD = 0.6). The least important factor
      was types of services (mean = 3.3, SD = 0.9), which covered the range of
      different services provided by or co-located with the practice. Frequent GP users
      and females had higher scores across all 5 scales, while the importance of care
      quality increased with age. CONCLUSIONS: When choosing a GP, information about
      the quality of care would be most useful to consumers. Respondents varied in the
      importance given to some factors including types of services, suggesting the need
      for a range of alternative primary care services.

PMID- 25565253
TI  - Balancing the false negative and positive rates in suspect screening with high
      resolution Orbitrap mass spectrometry using multivariate statistics.
AB  - Modern high-resolution mass spectrometry (HRMS) enables full-spectrum trace level
      analysis of emerging environmental organic contaminants. This raises the
      opportunity for post-acquisition suspect screening when no reference standards
      are a priori available. When setting up a conventional screening identification
      train based on successively different identification criteria including mass
      error and isotope fit, the false negative rate typically accumulates upon
      advancing through the decision tree. The challenge is thus to elaborate a well
      balanced screening, in which the different criteria are equally stringent,
      leading to a controllable number of false negatives. Presented is a novel suspect
      screening approach using liquid-chromatography Orbitrap HRMS. Based on a
      multivariate statistical model, the screening takes into account the accurate
      mass error of the mono isotopic ion and up to three isotopes, isotope ratios, and
      a peak/noise filter. As such, for the first time, controlling the overall false
      negative rate of the screening algorithm to a desired level (5% in this study) is
      achieved. Simultaneously, a well-balanced identification decision is guaranteed
      taking the different identification criteria as a whole in a holistic statistical
      approach. Taking into account 1, 2, and 3 isotopes decreases the false positive
      rate from 22, 2.8 to <0.3%, but the cost of increasing the median limits of
      identification from 200, 2000 to 2062 ng L(-1), respectively, should also be
      considered. As proof of concept, 7 biologically treated wastewaters were screened
      toward 77 suspect pharmaceuticals resulting in the indicative identification of
      25 suspects. Subsequently obtained reference standards allowed confirmation for
      19 out of these 25 pharmaceutical contaminants. 

PMID- 25565254
TI  - Neuroprotective and anti-inflammatory mechanisms are activated early in optic
      neuritis.
AB  - OBJECTIVE: The aim of the study was to investigate the expression of different
      immunological mediators in blood and CSF in patients with acute ON and to
      estimate whether they were implicated in pro- or anti-inflammatory or even
      regulatory reactions in comparison with a healthy control group (HC). METHODS:
      Sixty-four patients between 18 and 59 years of age suffering by acute ON, onset
      of <4 weeks, were included in the study. Visual tests and brain magnetic
      resonance imaging (MRI) were performed in ON. Blood and CSF samples were
      collected from untreated patients and from a gender- and age-matched voluntary HC
      (n = 32). The mRNA expression of distinct cytokines and neurotrophic factors was
      assessed by semi/quantitative real-time PCR (RT-PCR). RESULTS: Brain- and glial
      cell-derived neurotrophic factor (BDNF and GDNF) and interleukin 10 (IL-10)
      expression was significantly increased in the CSF compared to the blood in both
      ON and HC (P < 0.001). In the CSF increased levels of BDNF and GDNF of the ON
      group were positively correlated with the presence of oligoclonal bands (OB).
      Additionally, patients with gadolinium (gd+) lesions on brain MRI showed
      increased levels of IL-5 in blood (P = 0.03). CONCLUSION: Our data indicate that
      both immuno-regulatory and neuroprotective mechanisms may potentially take place
      relatively early in the course of the ON. The presence of neurotrophic factors in
      healthy CSF and their overexpression already during the acute phase of ON
      supports the alertness of CNS defence mechanisms ready to be activated during
      degenerative events, such as destruction of the myelin.

PMID- 25565256
TI  - Characterizing the importance of free space in the numerical human body models.
AB  - The geometric fidelity of the inner organs on finite-element model (FEM) of the
      human body and the choice to use discontinuous mesh engender the appearance of
      empty spaces that do not reflect the real-life situation of human body cavities.
      The aim of this study is to assess the influence of these empty spaces on the
      behavior of a simplified FEM built with three different structures in interaction
      which properties are relevant with the abdominal cavity. This FEM is made up of a
      large sphere (peritoneum) containing two hemispheres (liver and spleen). The
      space between peritoneum and inner organs was defined with two different
      approaches and assessed under impact conditions. The first is a meshfree space
      (Mfs) approach, e.g., consider the space as a perfect gas. The second approach,
      meshed space (MS), entailed adding volumetric elements in the empty space. From
      each approach, one optimal configuration was identified regarding the recorded
      force versus compression, the mobility of inner organs, and the space
      incompressibility. This space has a considerable influence on the behavior of the
      FEM and mainly on the applied loadings of inner organs (difference reaching 70%
      according to the configuration). For the first approach, the incompressible gas
      is designated because it guarantees space incompressibility (vf/vi = 1) and inner
      organs loading with the lowest delay (for high impact velocity: Peak force = 89
      N, compression 47%). For the second approach, the discontinuous volumetric mesh
      is preferred because it promotes space incompressibility (vf/vi = 0.94) and
      acceptable force reaction (for high impact velocity: Peak force = 97 N,
      compression 49%). The current study shows the importance of this space on the
      human FEMs cavities behavior and proposes two configurations able to be used in a
      future study including detailed FEM. 

PMID- 25565255
TI  - Metabotropic glutamate receptor 5 negative allosteric modulators: discovery of 2
      chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine
      (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases.
AB  - Negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5
      (mGlu5) have potential for the treatment of psychiatric diseases including
      depression, fragile X syndrome (FXS), anxiety, obsessive-compulsive disorders,
      and levodopa induced dyskinesia in Parkinson's disease. Herein we report the
      optimization of a weakly active screening hit 1 to the potent and selective
      compounds chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4
      ylethynyl]pyridine (basimglurant, 2) and 2-chloro-4-((2,5-dimethyl-1-(4
      (trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP, 3). Compound 2
      is active in a broad range of anxiety tests reaching the same efficacy but at a
      10- to 100-fold lower dose compared to diazepam and is characterized by favorable
      DMPK properties in rat and monkey as well as an excellent preclinical safety
      profile and is currently in phase II clinical studies for the treatment of
      depression and fragile X syndrome. Analogue 3 is the first reported mGlu5 NAM
      with a long half-life in rodents and is therefore an ideal tool compound for
      chronic studies in mice and rats. 

PMID- 25565257
TI  - In vitro and mouse studies support therapeutic utility of triiodothyroacetic acid
      in MCT8 deficiency.
AB  - MCT8 transports thyroid hormone (TH) across the plasma membrane. Mutations in
      MCT8 result in the Allan-Herndon-Dudley syndrome (AHDS), comprising severe
      psychomotor retardation and elevated serum T3 levels. As the neurological
      symptoms are most likely caused by a lack of TH transport into the CNS, the
      administration of a TH analogue which does not require MCT8 for cellular uptake
      may represent a therapeutic strategy. Here, we investigated the therapeutic
      potential of the biologically active T3 metabolite Triac (TA3) by studying TA3
      transport, metabolism and action both in vitro and in vivo. Incubation of SH-SY5Y
      neuroblastoma cells and MO3.13 oligodendrocytes with labeled substrates showed a
      time-dependent uptake of T3 and TA3. In intact SH-SY5Y cells, both T3 and TA3
      were degraded by endogenous type 3 deiodinase, and they influenced gene
      expression to a similar extent. Fibroblasts from MCT8 patients showed an impaired
      T3 uptake compared to controls, whereas TA3 uptake was similar in patient and
      control fibroblasts. In transfected cells, TA3 did not show significant transport
      by MCT8. Most importantly, treatment of athyroid Pax8 knockout mice and
      Mct8/Oatp1c1 double knockout mice between postnatal day 1 and 12 with TA3
      restored T3-dependent neural differentiation in the cerebral and cerebellar
      cortex indicating that TA3 can replace T3 in promoting brain development. In
      conclusion, we demonstrated uptake of TA3 in neuronal cells and in fibroblasts of
      MCT8 patients, and similar gene responses to T3 and TA3. This indicates that TA3
      bypasses MCT8 and may be used to improve the neural status of MCT8 patients.

PMID- 25565258
TI  - The effects of grape seed on apoptosis-related gene expression and oxidative
      stress in streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Diabetic nephropathy is the most common cause of end-stage renal
      disease. Emerging evidences indicate that many mechanistic pathways including
      apoptosis play an important role in the pathogenesis and progression of
      macrovascular and microvascular complications of diabetes mellitus. The aim of
      the present study is to show the effects of grape seed extract (GSE) on oxidative
      stress and apoptosis in the kidney of streptozotocin-induced diabetic rats.
      MATERIALS AND METHODS: The study included control group, diabetic group without
      treatment and diabetic group treated with GSE (n=7) group. GSE was given orally
      (100 mg/kg/day) for six weeks. Following parameters were evaluated; oxidative
      stress index, caspase 1, IL1-alpha, caspase 2, IL1-beta, BCL2-associated agonist
      of cell death (BAD), X-linked inhibitor of apoptosis (XIAP), DNA fragmentation
      factor, alpha subunit and beta bubunit (DFFA, DFFB), BH3 interacting domain death
      agonist (BID), caspase 6, Bcl2-like 1 (BCL-XL), caspase 8, tumor necrosis factor
      receptor superfamily, member 1 b (TNFRSF1B) and IAP-binding mitochondrial protein
      (DIABLO). RESULTS: Oxidative stress index levels were significantly increased in
      the kidney of diabetic group without treatment compared to control group, and
      decreased in diabetic+GSE group compared to diabetic group without treatment. In
      the kidney of diabetic group without treatment, caspase 1, IL-1 alpha, BAD, DFFA,
      DFFB and caspase-6 gene expressions were significantly higher compared to control
      group. In diabetic+GSE group caspase 1, caspase 2, XIAP, DFFA, BID, BCL-XL and
      TNFRSF1B genes were significantly decreased compared to control group.
      CONCLUSIONS: Grape seed reduces oxidative stress and apoptosis gene expression
      suggesting the protective effect on diabetic nephropathy.

PMID- 25565259
TI  - Pre-transplant low level HLA antibody shows a composite poor outcome in long-term
      outcome of renal transplant recipients.
AB  - To determine the significance of low-level DSA (donor specific antibody) in
      patients transplanted with negative cytotoxicity AHG (antihuman immunoglobulin)
      crossmatch, data from 279 patients who received a kidney transplant between July
      1999 and March 2006 were collected. All kidney recipients received ABO-compatible
      donors. A poor outcome was defined as any one of the following: death, Cr>2.0
      mmol/L, occurrence of a rejection episode. Luminex Screening and Single Antigen
      assays from Tepnel Life Codes were used to detect human leukocyte antigen
      antibodies on pre-transplant sera retrospectively. Twenty-four out of 279
      recipients demonstrated the presence of solid-phase DSA (MFI>1000) present pre
      transplant. In DSA+ group, the accumulated good versus poor outcome rate was 0.30
      versus 0.70, respectively. These rates were 0.49 and 0.51, respectively, in the
      DSA- group. The difference in composite poor outcome between DSA+ versus DSA-
      group was significant (p=0.030). The DSA- group had no difference in patient
      survival as compared to the DSA+ group (p=0.061). There is no statistically
      significant difference for either mortality or outcome results between high MFI
      (>2000) and low MFI (<=2000) groups. Our data suggest that solid-phase antibodies
      which are not strong enough to elicit a positive T-AHG crossmatch may influence
      long-term graft outcome.

PMID- 25565260
TI  - Disrupting diagnostic reasoning: do interruptions, instructions, and experience
      affect the diagnostic accuracy and response time of residents and emergency
      physicians?
AB  - PURPOSE: Others have suggested that increased time pressure, sometimes caused by
      interruptions, may result in increased diagnostic errors. The authors previously
      found, however, that increased time pressure alone does not result in increased
      errors, but they did not test the effect of interruptions. It is unclear whether
      experience modulates the combined effects of time pressure and interruptions.
      This study investigated whether increased time pressure, interruptions, and
      experience level affect diagnostic accuracy and response time. METHOD: In October
      2012, 152 residents were recruited at five Medical Council of Canada Qualifying
      Examination Part II test sites. Forty-six emergency physicians were recruited
      from one Canadian and one U.S. academic health center. Participants diagnosed 20
      written general medicine cases. They were randomly assigned to receive fast (time
      pressure) or slow condition instructions. Visual and auditory case interruptions
      were manipulated as a within-subject factor. RESULTS: Diagnostic accuracy was not
      affected by interruptions or time pressure but was related to experience level:
      Emergency physicians were more accurate (71%) than residents (43%) (F = 234.0, P
      < .0001) and responded more quickly (54 seconds) than residents (65 seconds) (F =
      9.0, P < .005). Response time was shorter for participants in the fast condition
      (55 seconds) than in the slow condition (73 seconds) (F = 22.2, P < .0001).
      Interruptions added about 8 seconds to response time. CONCLUSIONS: Experienced
      emergency physicians were both faster and more accurate than residents.
      Instructions to proceed quickly and interruptions had a small effect on response
      time but no effect on accuracy.

PMID- 25565261
TI  - Should medical students track former patients in the electronic health record? An
      emerging ethical conflict.
AB  - Medical students are increasingly using electronic health records (EHRs) in
      clerkships, and medical educators should seek opportunities to use this new
      technology to improve training. One such opportunity is the ability to "track"
      former patients in the EHR, defined as following up on patients in the EHR for
      educational purposes for a defined period of time after they have left one's
      direct care. This activity offers great promise in clinical training by enabling
      students to audit their diagnostic impressions and follow the clinical history of
      illness in a manner not possible in the era of paper charting. However, tracking
      raises important questions about the ethical use of protected health information,
      including concerns about compromising patient autonomy, resulting in a conflict
      between medical education and patient privacy. The authors offer critical
      analysis of arguments on both sides and discuss strategies to balance the ethical
      conflict by optimizing outcomes and mitigating harms. They observe that tracking
      improves training, thus offering long-lasting benefits to society, and is
      supported by the principle of distributive justice. They conclude that students
      should be permitted to track for educational purposes, but only with defined
      limits to safeguard patient autonomy, including obtaining permission from
      patients, having legitimate educational intent, and self-restricting review of
      records to those essential for training. Lastly, the authors observe that this
      conflict will become increasingly important with completion of the planned
      Nationwide Health Information Network and emphasize the need for national
      guidelines on tracking patients in an ethically appropriate manner. 

PMID- 25565262
TI  - Wisdom of the crowd: bright ideas and innovations from the teaching value and
      choosing wisely challenge.
AB  - PROBLEM: Medical education has been cited as both part of the problems facing,
      and part of the solution to reforming, the increasingly challenging U.S. health
      care system which is fraught with concerns regarding the quality and
      affordability of care. To teach value in ways that are impactful, sustainable,
      and scalable, the best and brightest ideas need to be shared such that educators
      can build on successful existing innovations. APPROACH: To identify the most
      promising innovations and bright ideas for teaching value to clinical trainees,
      the authors hosted the "Teaching Value and Choosing Wisely Challenge." The
      challenge used crowdsourcing methods to solicit scalable, pedagogical approaches
      from across North America, and then draw generalizable lessons. OUTCOMES: The
      authors received 74 submissions (28 innovations; 46 bright ideas) from 14
      students, 20 residents/fellows, 38 faculty members (ranging from instructors to
      full professors), and 2 nonclinical administrators. Submissions represented 14
      clinical disciplines including internal medicine, emergency medicine, surgery,
      pediatrics, obstetrics-gynecology, laboratory medicine, and pharmacy. Thirty-nine
      abstracts focused on graduate medical education, 15 addressed undergraduate
      medical education, and 20 applied to both. NEXT STEPS: The authors have
      solicited, shared, and described solutions for teaching high-value care to
      medical trainees. Challenge participants demonstrated commitment to improving
      value and ingenuity in addressing professional barriers to change. Further
      success requires strong local faculty champions and willing trainee participants.
      Additionally, the use of data to demonstrate the collective positive impact of
      these ideas and programs will be critical for sustaining pedagogical changes in
      the health professions.

PMID- 25565263
TI  - Is a career in medicine the right choice? The impact of a physician shadowing
      program on undergraduate premedical students.
AB  - PROBLEM: Undergraduate (i.e., baccalaureate) premedical students have limited
      exposure to clinical practice before applying to medical school-a shortcoming,
      given the personal and financial resources required to complete medical training.
      APPROACH: The Stanford Immersion in Medicine Series (SIMS) is a program that
      streamlines the completion of regulatory requirements for premedical students and
      allows them to develop one-on-one mentor-mentee relationships with practicing
      physicians. The program, offered quarterly since 2007, is an elective available
      for Stanford University sophomores, juniors, and seniors. Participants apply to
      the program and, if accepted, receive patient rights and professionalism
      training. Students shadow the physician they are paired with at least four times
      and submit a reflective essay about their experience.SIMS program coordinators
      administered surveys before and after shadowing to assess changes in students'
      perceptions and understanding of medical careers. OUTCOMES: The authors observed,
      in the 61 Stanford premedical students who participated in SIMS between March and
      June 2010 and completed both pre- and postprogram questionnaires, significant
      increases in familiarity with physician responsibilities and in understanding
      physician-patient interactions. The authors detected no significant changes in
      student commitment to pursuing medicine. Student perceptions of the value of
      shadowing-high both pre- and post shadowing-did not change. NEXT STEPS: Physician
      shadowing by premedical baccalaureate students appears to promote an
      understanding of physician roles and workplace challenges. Future studies should
      identify the ideal timing, format, and duration of shadowing to optimize the
      experience and allow students to make informed decisions about whether to pursue
      a medical career.

PMID- 25565264
TI  - Finding the middle path in tracking former patients in the electronic health
      record for the purpose of learning.
AB  - As medical trainees gain clinical experience, they increasingly form diagnoses
      based on their association with predisposing conditions and clinical features
      rather than pathophysiological explanations. Knowledge of these associations is
      housed as scripts in long-term memory, and data from the expertise literature
      imply that expert performance is largely explained by experts possessing more
      accurate scripts. In rotation-based clerkships, students typically spend a short
      period of time involved in the care of patients and are frequently deprived of
      the opportunity to observe the evolution and resolution of illness and the
      correct association between predisposing conditions, clinical features, and final
      diagnosis that is required for accurate script formation. Thanks to the
      introduction of an electronic health record (EHR), students now have the
      opportunity to track former patients until the final diagnosis and response to
      treatment is known. Although former patients are unlikely to benefit from being
      tracked by medical students, this type of learning experience may help students
      form more accurate scripts and, thus, improve their diagnostic performance on
      subsequent patients. But, because the purpose of EHRs is to improve clinical care
      of patients, is it ethically acceptable to allow students no longer involved in
      the care of patients to use these data solely for the purposes of learning? In
      this Commentary, the authors highlight the potential for ethical conflict
      whenever clinical care and teaching mingle, and discuss how these competing
      interests can still be balanced in the face of advancing technology by applying
      universal ethical principles and following the advice of Hippocrates. 

PMID- 25565265
TI  - Earlier immunomodulatory treatment is associated with better visual outcomes in a
      subset of patients with Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To evaluate clinical outcomes of first-line immunomodulatory therapy
      (IMT) and prednisone alone or late IMT in Vogt-Koyanagi-Harada disease. METHODS:
      Retrospective cohort study of 152 patients with Vogt-Koyanagi-Harada disease
      evaluated in a referral uveitis clinic in Chile from 1985 to 2011. Medical
      records of these patients were reviewed. Demographic data, clinical evaluation,
      type of treatment, functional outcomes, glucocorticoid (GC) dose and
      complications were recorded. Multivariate logistic regression was used to
      identify prognostic factors of poor response to GC. RESULTS: There were no
      significant differences between first-line IMT group and prednisone alone/late
      IMT group in terms of visual acuity (VA) improvement, complications and GC
      sparing effect. There was a trend for a higher frequency of systemic adverse
      effects leading to discontinuation of treatment in patients receiving IMT than in
      those receiving prednisone (14.6% and 6.5%, respectively). The subgroup of
      patients with poor response to GC who showed functional improvement had a
      significantly earlier time to IMT initiation than the patients who had no
      improvement. We identified following prognostic factors of poor response to GC:
      VA <= 20/200, fundus depigmentation, chronic disease and tinnitus at diagnosis.
      Patients with a prognostic factor (excluding tinnitus) and VA improvement had an
      earlier IMT initiation than those who had worse functional outcome. CONCLUSION:
      There were no differences in outcomes between first-line IMT and prednisone
      alone/late IMT in the entire VKH group. However, in a subset of patients, there
      was a significant better functional outcome with earlier IMT initiation.

PMID- 25565266
TI  - Dehydration, dissolution, and melting of cyclodextrin crystals.
AB  - Cyclodextrins are a family of oligosaccharides with a toroid shape that exhibit a
      unique ability of entrapping guest molecules in their internal cavity. Water is
      the primary guest molecule and is omnipresent in the crystalline phases
      stabilizing the overall architecture. Despite the presence of water molecules
      inside the cavity, cyclodextrins provide a hydrophobic environment where poorly
      soluble molecules can easily fit. In this investigation we put in evidence
      different types of water in the hydrated alpha-, beta-, and gamma-cyclodextrin
      crystals. Thermogravimetric measurements identify various binding sites of water
      and highlight the difference between the crystals equilibrated under various
      humid atmospheres. We establish by microcalorimetry the limit of solubility
      versus temperature and measure for the first time the melting temperatures of the
      hydrated crystals. Dissolution and melting enthalpies are derived and the
      solubility curves are compared to existing literature. The specific features of
      each cyclodextrin are underlined. 

PMID- 25565267
TI  - Theoretical investigation of enantioselectivity of cage-like supramolecular
      assembly: the insights into the shape complementarity and host-guest interaction.
AB  - Enantioselectivity in the aza-Cope rearrangement of a guest molecule encapsulated
      in a cage-like supramolecular assembly [Ga4 L6 ](12-) [L = 1,5-bis(2',3'
      dihydroxybenzamido)naphthalene] is investigated using density functional theory
      and ab initio molecular orbital calculations. Reaction pathways leading to R- and
      S-enantiomers encapsulated in the [Ga4 L6 ](12-) are explored. The reaction
      barriers and the stabilities of the prochiral structures differed in the [Ga4 L6
      ](12-) , resulting that the product with an R structure is favorably produced in
      the Delta-structure [Ga4 L6 ](12-) . The large energy difference in the prochiral
      structures in the [Ga4 L6 ](12-) was attributed to the deformation of the bulky
      substituent. The host-guest interaction energy raises the reaction barrier for
      the product with an S structure. The previous study suggested that the different
      stability of the prochiral substrates in the assembly was the origin of the
      enantioselectivity, and the suggestion is supported by our computational finding.
      In addition, our results show that the difference in the reaction barriers also
      importantly contributes to the enantioselectivity.

PMID- 25565268
TI  - Building a pan-genome reference for a population.
AB  - A reference genome is a high quality individual genome that is used as a
      coordinate system for the genomes of a population, or genomes of closely related
      subspecies. Given a set of genomes partitioned by homology into alignment blocks
      we formalize the problem of ordering and orienting the blocks such that the
      resulting ordering maximally agrees with the underlying genomes' ordering and
      orientation, creating a pan-genome reference ordering. We show this problem is NP
      hard, but also demonstrate, empirically and within simulations, the performance
      of heuristic algorithms based upon a cactus graph decomposition to find locally
      maximal solutions. We describe an extension of our Cactus software to create a
      pan-genome reference for whole genome alignments, and demonstrate how it can be
      used to create novel genome browser visualizations using human variation data as
      a test. In addition, we test the use of a pan-genome for describing variations
      and as a reference for read mapping. 

PMID- 25565269
TI  - A phase II trial of second-line axitinib following prior antiangiogenic therapy
      in advanced hepatocellular carcinoma.
AB  - BACKGROUND: Second-line treatment options in advanced hepatocellular carcinoma
      (HCC) are limited. Axitinib, a selective potent tyrosine kinase inhibitor (TKI)
      of vascular endothelial growth factor VEGF) receptors 1, 2, and 3, merits
      exploration in HCC. METHODS: This was a single-arm phase II trial of axitinib in
      advanced HCC. Eligible patients were Child-Pugh A/B7, with measurable progressive
      disease after TKIs/antiangiogenic drugs. Axitinib was started at 5 mg twice daily
      orally, titrated from 2 to 10 mg twice daily as tolerated. The primary end point
      was tumor control at 16 weeks by RECIST1.1; secondary end points were response
      rate, comparing response by RECIST1.1 to Choi and modified RECIST, exploring
      dynamic contrast-enhanced imaging models, safety, progression-free (PFS), and
      overall survival (OS). RESULTS: Thirty patients were treated. Of 26 patients
      evaluable for response, there were 3 partial responses (PR) per RECIST1.1; 13 PR
      by Choi, 6 PR and 1 complete response by modified RECIST. Tumor control rate at
      16 weeks was 42.3%. Two-week perfusion changes were noted on functional imaging.
      Of 21 patients with evaluable alpha-fetoprotein response, 43% had >50% decrease
      from baseline. Most common axitinib-related grade 3/4 adverse events (AEs) were
      hypertension, thrombocytopenia and diarrhea. Of 11 patients with any grade
      hypertension, 7 had disease control >36 wks. Four patients discontinued treatment
      due to AEs. Median PFS was 3.6 months. Median OS was 7.1 months. CONCLUSIONS:
      With 42.3% tumor control at 16 weeks, primary endpoint was met. Axitinib has
      shown encouraging tolerable clinical activity in VEGF-pretreated HCC patients but
      further study should be in a selected population incorporating potential
      biomarkers of response.

PMID- 25565270
TI  - Dorsal hippocampus infusions of CNQX into the dentate gyrus disrupt expression of
      trace fear conditioning.
AB  - The hippocampus is essential for the consolidation of some explicit long-term
      memories, including trace conditioning. Lesions and pharmacological manipulations
      of the dorsal hippocampus (DH) have provided strong evidence for its involvement
      in the acquisition and expression of trace fear memories. However, no studies
      have specifically targeted DH subregions [CA1 and dentate gyrus (DG)] to
      determine their involvement in trace fear conditioning. In the present study,
      rats received bilateral cannulation targeting either the DG or CA1 of the DH.
      Following surgery, animals were trace fear conditioned. Forty-eight hours
      following training, rats received bilateral infusions of the AMPA/kainate
      glutamate receptor antagonist, CNQX, or vehicle. Following the infusion, rats
      were placed in a novel context for the tone test. Rats that received CNQX into
      the DG froze significantly less during the tone and trace interval as compared to
      controls. Rats that received CNQX into the DH CA1 showed no difference in
      freezing during the tone or trace interval as compared to controls. These data
      support a role for the DG in the expression of trace tone fear conditioning.

PMID- 25565271
TI  - An artificial blood vessel implanted three-dimensional microsystem for modeling
      transvascular migration of tumor cells.
AB  - Reproducing a tumor microenvironment consisting of blood vessels and tumor cells
      for modeling tumor invasion in vitro is particularly challenging. Here, we report
      an artificial blood vessel implanted 3D microfluidic system for reproducing
      transvascular migration of tumor cells. The transparent, porous and elastic
      artificial blood vessels are obtained by constructing polysaccharide cellulose
      based microtubes using a chitosan sacrificial template, and possess excellent
      cytocompatibility, permeability, and mechanical characteristics. The artificial
      blood vessels are then fully implanted into the collagen matrix to reconstruct
      the 3D microsystem for modeling transvascular migration of tumor cells. Well
      defined simulated vascular lumens were obtained by proliferation of the human
      umbilical vein endothelial cells (HUVECs) lining the artificial blood vessels,
      which enables us to reproduce structures and functions of blood vessels and
      replicate various hemodynamic parameters. Based on this model, the adhesion and
      transvascular migration of tumor cells across the artificial blood vessel have
      been well reproduced. 

PMID- 25565272
TI  - Polymorphisms of cell cycle control genes influence the development of sporadic
      medullary thyroid carcinoma.
AB  - BACKGROUND: The role of key cell cycle regulation genes such as, CDKN1B, CDKN2A,
      CDKN2B, and CDKN2C in sporadic medullary thyroid carcinoma (s-MTC) is still
      largely unknown. METHODS: In order to evaluate the influence of inherited
      polymorphisms of these genes on the pathogenesis of s-MTC, we used TaqMan SNP
      genotyping to examine 45 s-MTC patients carefully matched with 98 controls.
      RESULTS: A multivariate logistic regression analysis demonstrated that CDKN1B and
      CDKN2A genes were related to s-MTC susceptibility. The rs2066827*GT+GG CDKN1B
      genotype was more frequent in s-MTC patients (62.22%) than in controls (40.21%),
      increasing the susceptibility to s-MTC (OR=2.47; 95% CI=1.048-5.833; P=0.038). By
      contrast, the rs11515*CG+GG of CDKN2A gene was more frequent in the controls
      (32.65%) than in patients (15.56%), reducing the risk for s-MTC (OR=0.174; 95%
      CI=0.048-0.627; P=0.0075). A stepwise regression analysis indicated that two
      genotypes together could explain 11% of the total s-MTC risk. In addition, a
      relationship was found between disease progression and the presence of
      alterations in the CDKN1A (rs1801270), CDKN2C (rs12885), and CDKN2B (rs1063192)
      genes. WT rs1801270 CDKN1A patients presented extrathyroidal tumor extension more
      frequently (92%) than polymorphic CDKN1A rs1801270 patients (50%; P=0.0376).
      Patients with the WT CDKN2C gene (rs12885) presented larger tumors (2.9+/-1.8 cm)
      than polymorphic patients (1.5+/-0.7 cm; P=0.0324). On the other hand, patients
      with the polymorphic CDKN2B gene (rs1063192) presented distant metastases (36.3%;
      P=0.0261). CONCLUSION: In summary, we demonstrated that CDKN1B and CDKN2A genes
      are associated with susceptibility, whereas the inherited genetic profile of
      CDKN1A, CDKN2B, and CDKN2C is associated with aggressive features of tumors. This
      study suggests that profiling cell cycle genes may help define the risk and
      characterize s-MTC aggressiveness.

PMID- 25565274
TI  - Three-dimensional reconstruction of corticospinal tract using one-photon confocal
      microscopy acquisition allows detection of axonal disruption in spinal cord
      injury.
AB  - The principal motor tract involved in mammalian locomotor activities is known as
      the corticospinal tract (CST), which starts in the brain motor cortex (upper
      motor neuron), extends its axons across the brain to brainstem and finally
      reaches different regions of spinal cord, contacting the lower motor neurons.
      Visualization of the CST is essential to carry out studies in different kinds of
      pathologies such as spinal cord injury or multiple sclerosis. At present, most
      studies of axon structure and/or integrity that involve histological tissue
      sectioning present the problem of finding the region where the CST is
      predominant. To solve this problem, one could use a novel technique to make the
      tissues transparent and observe them directly without histological sectioning.
      However, the disadvantage of this procedure is the need of costly and
      nonconventional equipment, such as two-photon fluorescence microscopy or
      ultramicroscopy to perform the image acquisition. Here, we show that labeling the
      CST with FluoroRuby in the motor cortex and then performing the clearing
      technique, the z-acquisition of the entire CST in unsectioned tissue followed by
      three-dimensional reconstruction can be carried out by standard one-photon
      confocal microscopy, with yields similar to those obtained by two-photon
      microscopy. In addition, we present an example of the application of this method
      in a spinal cord injury model, where the disruption of CST is shown at the lesion
      site.

PMID- 25565273
TI  - Yeast cell wall extract induces disease resistance against bacterial and fungal
      pathogens in Arabidopsis thaliana and Brassica crop.
AB  - Housaku Monogatari (HM) is a plant activator prepared from a yeast cell wall
      extract. We examined the efficacy of HM application and observed that HM
      treatment increased the resistance of Arabidopsis thaliana and Brassica rapa
      leaves to bacterial and fungal infections. HM reduced the severity of bacterial
      leaf spot and anthracnose on A. thaliana and Brassica crop leaves with protective
      effects. In addition, gene expression analysis of A. thaliana plants after
      treatment with HM indicated increased expression of several plant defense-related
      genes. HM treatment appears to induce early activation of jasmonate/ethylene and
      late activation of salicylic acid (SA) pathways. Analysis using signaling mutants
      revealed that HM required SA accumulation and SA signaling to facilitate
      resistance to the bacterial pathogen Pseudomonas syringae pv. maculicola and the
      fungal pathogen Colletotrichum higginsianum. In addition, HM-induced resistance
      conferred chitin-independent disease resistance to bacterial pathogens in A.
      thaliana. These results suggest that HM contains multiple microbe-associated
      molecular patterns that activate defense responses in plants. These findings
      suggest that the application of HM is a useful tool that may facilitate new
      disease control methods. 

PMID- 25565275
TI  - Influence of temperature during grain filling on gluten viscoelastic properties
      and gluten protein composition.
AB  - BACKGROUND: The aim of this study was to investigate the effects of low to
      moderate temperatures on gluten functionality and gluten protein composition.
      Four spring wheat cultivars were grown in climate chambers with three temperature
      regimes (day/night temperatures of 13/10, 18/15 and 23/20  degrees C) during
      grain filling. RESULTS: The temperature strongly influenced grain weight and
      protein content. Gluten quality measured by maximum resistance to extension (Rmax
      ) was highest in three cultivars grown at 13  degrees C. Rmax was positively
      correlated with the proportion of sodium dodecyl sulfate-unextractable polymeric
      proteins (%UPP). The proportions of omega-gliadins and D-type low-molecular
      weight glutenin subunits (LMW-GS) increased and the proportions of alpha- and
      gamma-gliadins and B-type LMW-GS decreased with higher temperature, while the
      proportion of high-molecular-weight glutenin subunits (HMW-GS) was constant
      between temperatures. The cultivar Berserk had strong and constant Rmax between
      the different temperatures. CONCLUSION: Constant low temperature, even as low as
      13  degrees C, had no negative effects on gluten quality. The observed variation
      in Rmax related to temperature could be explained more by %UPP than by changes in
      the proportions of HMW-GS or other gluten proteins. The four cultivars responded
      differently to temperature, as gluten from Berserk was stronger and more stable
      over a wide range of temperatures.

PMID- 25565276
TI  - A robust method for increasing Fc glycan high mannose level of recombinant
      antibodies.
AB  - High mannose (HM) glycoforms on antibody Fc glycan are recognized as critical
      quality attributes for therapeutic antibody products. Methods to control HM have
      been largely empirical, and it is challenging to target a desired HM level during
      antibody process development. A novel and robust method to increase antibody HM
      glycoforms is demonstrated in this study using multiple antibodies and cell lines
      without adversely impacting cell culture performance, including viable cell
      density, viability, and protein titer. This approach utilizes mannose as a carbon
      source and the ratio of mannose to total hexose (glucose and mannose) in feed
      media determines the extent of HM glycan content of an antibody expressed in cell
      culture. Scale-up of this strategy from 3 mL small scale plate to bioreactor (1.5
      L) is also demonstrated with comparable results. Further full glycan map analysis
      shows that HM increase predominantly correlates with the decrease in G0F glycan,
      with minimum impact on other glycoforms. Possible hypotheses for the HM glycan
      modulation using mannose as carbon source are also discussed. Three pathways,
      including GDP-mannose biosynthesis, early protein glycosylation and UDP-N
      acetylglucosamine biosynthesis, might be involved and contribute to this HM
      modulation.

PMID- 25565277
TI  - Virtually instantaneous, room-temperature [(11)C]-cyanation using biaryl
      phosphine Pd(0) complexes.
AB  - A new radiosynthetic protocol for the preparation of [(11)C]aryl nitriles has
      been developed. This process is based on the direct reaction of in situ prepared
      L.Pd(Ar)X complexes (L = biaryl phosphine) with [(11)C]HCN. The strategy is
      operationally simple, exhibits a remarkably wide substrate scope with short
      reaction times, and demonstrates superior reactivity compared to previously
      reported systems. With this procedure, a variety of [(11)C]nitrile-containing
      pharmaceuticals were prepared with high radiochemical efficiency. 

PMID- 25565278
TI  - Factors affecting community participation in the CDTI program in Morogoro,
      Tanzania.
AB  - BACKGROUND: Up to 4 million people in Tanzania are at risk for the parasitic
      disease onchocerciasis. A treatment program, Community-Directed Treatment with
      Ivermectin (CDTI), has made significant gains in prevention and treatment.
      Understanding factors affecting participation could help boost treatment coverage
      and sustain gains made in controlling onchocerciasis in endemic areas. PURPOSE:
      To explore community-perceived factors related to participation in and
      sustainability of the CDTI program in southwest Tanzania. METHODS: Multilevel
      triangulation design using surveys, focus group discussions (FGDs), and
      semistructured interviews to collect data in two villages in the Morogoro Rural
      District of Tanzania. In total, 456 villagers participated in the survey and 42
      in FDGs. Five community-directed distributors (CDDs) and three community health
      workers were interviewed. FINDINGS: High levels of awareness of onchocerciasis
      (90%) and methods of prevention and treatment (95%) were reported. Over 75% of
      participants knew how ivermectin was distributed and 74% have taken the drug.
      Over 90% of villagers knew that distribution of the drug was for treatment and
      prevention. Only 43% knew the cause of onchocerciasis. Through FGDs, villagers
      reported barriers to participation, including lack of comprehensive understanding
      of the disease, fears of medication, distrust of the method determining dose,
      lack of health education materials, insufficient CDD-resident communication, and
      inflexible drug distribution mechanisms. CONCLUSIONS: Sustaining programs without
      supporting growth of CDDs and reinforcing education of communities could lead to
      a decrease in treatment and an increase in the public health threat. This
      research uncovered a need for more effective community education and
      sensitization. CLINICAL RELEVANCE: Understanding barriers to participation in
      community-based programs can assist public health and community health nurses and
      key stakeholders including Ministries of Health and local and regional health
      systems in the development of education and support materials to enhance health
      literacy and encourage program participation.

PMID- 25565280
TI  - Imaging chemical neurotransmission with genetically encoded fluorescent sensors.
AB  - A major challenge in neuroscience is to decipher the logic of neural circuitry
      and to link it to learning, memory, and behavior. Synaptic transmission is a
      critical event underlying information processing within neural circuitry. In the
      extracellular space, the concentrations and distributions of excitatory,
      inhibitory, and modulatory neurotransmitters impact signal integration, which in
      turn shapes and refines the function of neural networks. Thus, the determination
      of the spatiotemporal relationships between these chemical signals with synaptic
      resolution in the intact brain is essential to decipher the codes for
      transferring information across circuitry and systems. Here, we review approaches
      and probes that have been employed to determine the spatial and temporal extent
      of neurotransmitter dynamics in the brain. We specifically focus on the design,
      screening, characterization, and application of genetically encoded indicators
      directly probing glutamate, the most abundant excitatory neurotransmitter. These
      indicators provide synaptic resolution of glutamate dynamics with cell-type
      specificity. We also discuss strategies for developing a suite of genetically
      encoded probes for a variety of neurotransmitters and neuromodulators.

PMID- 25565281
TI  - Oxidation-induced water-solubilization and chemical functionalization of
      fullerenes C60, Gd@C60 and Gd@C82: atomistic insights into the formation
      mechanisms and structures of fullerenols synthesized by different methods.
AB  - Water-solubilization is the prerequisite to endow the pristinely hydrophobic
      fullerenes with biocompatibility and biofunctionality, which has been widely
      applied to derive fullerene-based nanomaterials for biomedical applications.
      Oxidation reactions using O2 and H2O2 are the most commonly used approaches to
      this end, through which fullerenols with different structural features can be
      obtained. Despite the progress in the syntheses and bioapplications of
      fullerenols, their formation mechanisms and structures at the atomic level, which
      substantialize their physical properties and biofunctions, have been little
      understood. Using density functional theory calculations, we comparatively study
      the mechanisms and product structures for the oxidations of C60, Gd@C60 and
      Gd@C82 using both O2 and H2O2 as oxidizing agents under both neutral and alkaline
      aqueous conditions. We predict the formation mechanisms and product structures
      corresponding to the different synthetic conditions. Briefly, the H2O2 oxidations
      of C60, Gd@C60 and Gd@C82 under neutral conditions do not occur readily at room
      temperature because of the high energy barriers, whereas the H2O2 oxidations can
      readily proceed under alkaline conditions. The oxygen-containing groups of the
      fullerenols obtained under these conditions include hydroxyl, carbonyl,
      hemiacetal and deprotonated vic-diol. In contrast, through O2 oxidation under
      alkaline conditions, the most probable oxygen-containing groups for C60
      fullerenols are epoxide and deprotonated vic-diol, and those for Gd@C60 and
      Gd@C82 fullerenols are hydroxyls and carbonyls. The results explain a wide range
      of experimental findings reported before. More importantly, they provide
      atomistic-level insights into the formation mechanisms and structures for various
      fullerenols, which are of fundamental interest for understanding their biomedical
      applications in the future. 

PMID- 25565279
TI  - Deceptive desmas: molecular phylogenetics suggests a new classification and
      uncovers convergent evolution of lithistid demosponges.
AB  - Reconciling the fossil record with molecular phylogenies to enhance the
      understanding of animal evolution is a challenging task, especially for taxa with
      a mostly poor fossil record, such as sponges (Porifera). 'Lithistida', a
      polyphyletic group of recent and fossil sponges, are an exception as they provide
      the richest fossil record among demosponges. Lithistids, currently encompassing
      13 families, 41 genera and >300 recent species, are defined by the common
      possession of peculiar siliceous spicules (desmas) that characteristically form
      rigid articulated skeletons. Their phylogenetic relationships are to a large
      extent unresolved and there has been no (taxonomically) comprehensive analysis to
      formally reallocate lithistid taxa to their closest relatives. This study, based
      on the most comprehensive molecular and morphological investigation of
      'lithistid' demosponges to date, corroborates some previous weakly-supported
      hypotheses, and provides novel insights into the evolutionary relationships of
      the previous 'order Lithistida'. Based on molecular data (partial mtDNA CO1 and
      28S rDNA sequences), we show that 8 out of 13 'Lithistida' families belong to the
      order Astrophorida, whereas Scleritodermidae and Siphonidiidae form a separate
      monophyletic clade within Tetractinellida. Most lithistid astrophorids are
      dispersed between different clades of the Astrophorida and we propose to formally
      reallocate them, respectively. Corallistidae, Theonellidae and Phymatellidae are
      monophyletic, whereas the families Pleromidae and Scleritodermidae are
      polyphyletic. Family Desmanthidae is polyphyletic and groups within
      Halichondriidae--we formally propose a reallocation. The sister group
      relationship of the family Vetulinidae to Spongillida is confirmed and we propose
      here for the first time to include Vetulina into a new Order Sphaerocladina.
      Megascleres and microscleres possibly evolved and/or were lost several times
      independently in different 'lithistid' taxa, and microscleres might at least be
      four times more likely lost than megascleres. Desma spicules occasionally may
      have undergone secondary losses too. Our study provides a framework for further
      detailed investigations of this important demosponge group.

PMID- 25565282
TI  - Erinacerins C-L, isoindolin-1-ones with alpha-glucosidase inhibitory activity
      from cultures of the medicinal mushroom Hericium erinaceus.
AB  - The well-known edible and medicinal mushroom Hericium erinaceus produces various
      bioactive secondary metabolites. Ten new isoindolin-1-ones, named erinacerins C-L
      (1-10), together with (E)-5-(3,7-dimethylocta-2,6-dien-1-yl)-4-hydroxy-6-methoxy
      2-phenethylisoindolin-1-one (11) were isolated from the solid culture of H.
      erinaceus. The structures of new metabolites were established by spectroscopic
      methods. The absolute configurations of 3, 4, 9, and 10 were assigned by
      comparing their specific rotations with those of related phthalimidines (13-20).
      Compounds 5 and 6, 7 and 8, and 9 and 10 are double-bond positional isomers. In a
      alpha-glucosidase inhibition assay, compounds 2-11 showed inhibitory activity
      with IC50 values ranging from 5.3 to 145.1 MUM. Preliminary structure-activity
      analysis indicated that the terpenoid side chain and the phenolic hydroxy groups
      contributed greatly to the alpha-glucosidase inhibitory activity of 1-11. In a
      cytotoxicity assay, compound 11 also presented weak cytotoxicity against two cell
      lines, A549 and HeLa, with IC50 values of 49.0 and 40.5 MUM. 

PMID- 25565284
TI  - Update on surgical management of adult inferior turbinate hypertrophy.
AB  - PURPOSE OF REVIEW: There are numerous surgical managements of hypertrophic
      inferior turbinate. Controversy still exists involving the optimal surgical
      technique for hypertrophic inferior turbinate. The current review will discuss
      the most commonly used techniques for turbinate surgery and highlight their
      recently published clinical outcomes. RECENT FINDINGS: Microdebrider-assisted
      turbinoplasty, along with total removal of inferior turbinate mucosa, turned out
      to have no negative impact on healing time and no adverse postoperative events.
      The majority of recently published studies were focused on surgical outcomes of
      radiofrequency ablation. It appears that radiofrequency ablation could improve
      nasal resistance, sense of smell, and nasal mucociliary function. A 1470-nm diode
      laser was found superior to a conventional 940-nm diode laser in reducing scar
      formation. Ultrasonic bone aspirator was used to manage hypertrophic inferior
      turbinate caused by bone enlargement. Few recent literatures report turbinectomy.
      SUMMARY: Inferior turbinate surgery offers benefit and improves nasal obstruction
      in patients with hypertrophic inferior turbinate refractory to medical treatment.
      Rigorously designed study including subjective and objective measurements,
      control or comparison group, and long-term follow-up should be carried out in the
      future.

PMID- 25565283
TI  - Fungi from metal-polluted streams may have high ability to cope with the
      oxidative stress induced by copper oxide nanoparticles.
AB  - Increased commercialization of products based on metal oxide nanoparticles
      increases the likelihood that these nanoparticles will be released into aquatic
      environments, thus making relevant the assessment of their potential impacts on
      aquatic biota. Aquatic fungi are distributed worldwide and play a key role in
      organic matter turnover in freshwater ecosystems. The present study investigated
      the impacts of copper oxide spherical nanoparticles (CuO-NPs; <50 nm powder, 5
      levels <=200 mg/L) on cellular targets and antioxidant defenses in 5 fungal
      isolates collected from metal-polluted or nonpolluted streams. The CuO-NPs
      induced oxidative stress in aquatic fungi, as evidenced by intracellular
      accumulation of reactive oxygen species, and led to plasma membrane damage and
      DNA strand breaks in a concentration-dependent manner. Effects were more
      pronounced with a longer exposure time (3 d vs 10 d). Under CuO-NP exposure,
      mycelia of fungi collected from metal-polluted streams showed less oxidative
      stress and higher activities of superoxide dismutase and glutathione reductase
      compared with fungi from nonpolluted streams. The latter fungi responded to CuO
      NPs with a stronger stimulation of glutathione peroxidase activity. These
      findings may indicate that fungi isolated from metal-polluted streams had a
      greater ability to maintain the pool of reduced glutathione than those from
      nonpolluted streams. Overall, results suggest that populations adapted to metals
      may develop mechanisms to cope with the oxidative stress induced by metal
      nanoparticles.

PMID- 25565285
TI  - The role of nasal treatments in snoring and obstructive sleep apnoea.
AB  - PURPOSE OF REVIEW: This review highlights recent advances and views on the role
      of the nose in snoring and obstructive sleep apnoea. RECENT FINDINGS: Recent
      reviews and past randomized controlled trials generally agree that nasal surgery
      may improve quality of life in snoring and obstructive sleep apnoea. There have
      been no published randomized controlled trials regarding nasal treatments in
      snoring or obstructive sleep apnoea in the past year. SUMMARY: Snoring and
      obstructive sleep apnoea are upper airway disorders in which the role of the nose
      has been well researched. Studies support that nasal surgery improves quality of
      life in snoring, but it may not lead to resolution of snoring. Likewise, nasal
      treatments for obstructive sleep apnoea increase the quality of life and
      treatment compliance in some patients. Further stratification of patients who may
      benefit from nasal intervention may clarify the role of nasal surgery.

PMID- 25565286
TI  - Long-term outcomes in endoscopic dacryocystorhinostomy.
AB  - PURPOSE OF REVIEW: This study reviews the current body of literature with recent
      updates and briefly describes the powered endoscopic dacryocystorhinostomy (DCR)
      approach. RECENT FINDINGS: This review highlights recent studies including a meta
      analysis of outcomes in DCR approaches, and compares each method to external DCR.
      When analyzed by method, endoscopic DCR with powered instrumentation success
      rates are comparable to the external approach, whereas the laser-assisted
      endoscopic DCR had a lower success rate. Additionally, several studies have
      demonstrated that long-term results in powered endoscopic DCR compare favorably
      with external approach in both primary and revision cases. SUMMARY: Endoscopic
      DCR with powered instrumentation is comparable to external DCR and also allows
      simultaneous adjunctive procedures while avoiding external scar. The powered
      endoscopic approach to DCR and methods to optimize success are described.

PMID- 25565287
TI  - The expanded endonasal approach for the treatment of intracranial skull base
      disease in the pediatric population.
AB  - PURPOSE OF REVIEW: To review the current literature on the expanded endonasal
      approach for pediatric skull base lesions. RECENT FINDINGS: This review examines
      the currently published outcomes of pediatric endoscopic skull base surgery. It
      specifically reviews the anatomic considerations of pediatric patients, growth
      considerations in pediatric patients, reconstructive options and limitations, and
      the use of image guidance. In addition, this review provides some suggestions for
      approaching skull base lesions in pediatric patients, based on both experience
      and the current body of literature. SUMMARY: The expanded endonasal approach for
      pediatric skull base lesions is a well tolerated and reliable method for the
      treatment of children with midline nasal masses. With improvements in technology
      and technique, this approach has become increasingly common in high-volume skull
      base centers as a well tolerated alternative to traditional open approaches.

PMID- 25565288
TI  - The utility of lumbar drains in modern endoscopic skull base surgery.
AB  - PURPOSE OF REVIEW: Lumbar drains were once routinely used for cerebrospinal fluid
      (CSF) diversion in endoscopic skull base reconstruction. The vascularized
      pedicled nasoseptal flap has now become the reconstructive workhorse in the
      setting of high-flow leaks. High-flow CSF leaks occur when there is violation of
      a cistern or ventricle. As lumbar drains have the potential for significant
      complications and the rate of postoperative CSF leak has decreased with the use
      of vascularized flaps, lumbar drain use has been challenged. RECENT FINDINGS:
      Lumbar drains have a reported 3% major and 5% minor complication rates. Two
      recent studies reviewed their postoperative CSF leak rates after reconstruction
      of high-flow leaks. Garcia-Navarro described 46 cases in which a lumbar drain was
      placed in 67% of patients with two postoperative CSF leaks, one in each group.
      Eloy et al. described 59 patients without lumbar drain and reported no
      postoperative CSF leaks. SUMMARY: Lumbar drains are not necessary in the settings
      of low-flow CSF leaks or even in all high-flow leaks. We consider the use of a
      lumbar drain in settings wherein a high-flow leak is encountered or anticipated
      and the patient has other risk factors that may make the risk of postoperative
      CSF leak higher or closure of the leak more difficult.

PMID- 25565291
TI  - Catalytic asymmetric hydrogenation of pyrimidines.
AB  - The asymmetric hydrogenation of pyrimidines proceeded with high
      enantioselectivity (up to 99% ee) using an iridium catalyst composed of
      [IrCl(cod)]2, a ferrocene-containing chiral diphosphine ligand (Josiphos),
      iodine, and Yb(OTf)3 (cod = 1,5-cyclooctadiene). The chiral catalyst converted
      various 4-substituted pyrimidines into chiral 1,4,5,6-tetrahydropyrimidines in
      high yield. The lanthanide triflate is crucial for achieving the high
      enantioselectivity as well as for activating the heteroarene substrate.

PMID- 25565292
TI  - Terahertz spectroscopy of 2,4-dinitrotoluene over a wide temperature range (7-245
      K).
AB  - Previous THz spectroscopy of the TNT explosive precursor, 2,4-dinitrotoluene
      (DNT), has been restricted to room temperature (apart from one set of data at 11
      K). Here, for the first time, we investigate the spectrum as the temperature is
      systematically varied, from 7 to 245 K. Many new features appear in the spectrum
      on cooling below room temperature. As well as the five absorption lines observed
      previously, we observe five additional lines. In addition, a new room-temperature
      line at 8.52 THz (281 cm(-1)) is observed. Six of the lines red-shift with
      temperature and four of them blue-shift. The blue shift is explained by interplay
      between intramolecular and intermolecular hydrogen bonds. The variation in line
      width and line intensity with temperature is not systematic, although a
      conspicuous decrease in line intensity with temperature is observed in all cases.
      Modeling with hybrid PBE0 and TPSSh functionals helps identify absorption modes. 

PMID- 25565290
TI  - Making sense of change: patients' views of diabetes and GP-led integrated
      diabetes care.
AB  - BACKGROUND: Health system reform is directed towards better management of
      diabetes. However, change can be difficult, and patients' perspectives are a key
      aspect of implementing change. OBJECTIVE: This study investigated patients'
      perceptions and experiences of type 2 diabetes (T2DM), self-care and engagement
      with GP-led integrated diabetes care. DESIGN: Qualitative interviews were
      conducted with purposively selected patients with T2DM following their initial
      medical appointment in the new model of care. Normalization process theory was
      used to orientate the thematic analysis, to explain the work of implementing
      change. SETTING: Two specialist GP-based complex diabetes services in primary
      care in Brisbane, Australia. PARTICIPANTS: Intervention group patients (n = 30)
      in a randomized controlled trial to evaluate a model of GP-led integrated care
      for complex T2DM. MAIN OUTCOME MEASURES: Participants' experiences and
      perceptions of diabetes management and a GP-led model of care. RESULTS: Three
      themes were identified: sensibility of change, 'diabetic life' and diabetes care
      alliance. The imperative of change made sense, but some participants experienced
      dissonance between this rational view and their lived reality. Diabetes invaded
      life, revealing incongruities between participants' values and living with
      diabetes. They appreciated a flexible and personalized approach to care.
      DISCUSSION: Participants responded to advice in ways that seemed rational within
      the complexities of their life context. Their diabetes partnerships with health
      professionals coupled providers' biomedical expertise with patients' contextual
      expertise. CONCLUSIONS: Learning to manage relationships with various health
      professionals adds to patients' diabetes-related work. Providers need to adopt a
      flexible, interactive approach and foster trust, to enable better diabetes care.

PMID- 25565293
TI  - Adrenal androgen excess and body mass index in polycystic ovary syndrome.
AB  - Context: Adrenal hyperandrogenism affects around 25% of polycystic ovary syndrome
      (PCOS) patients but its relation to obesity is not totally understood. Objective:
      To assess dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate
      (DHEAS) levels in relation to body mass index (BMI) in PCOS. Design: Prospective
      observational study. Setting: Institutional practice at an Obstetrics/Gynecology
      hospital. Patients or Other Participants: This study included 136 PCOS patients,
      20-35 years old, and 42 matched-age control women. The participants were
      classified with the BMI cutoff value of 27 kg/m2 as follows: 1) high-BMI PCOS
      patients; 2) low-BMI PCOS patients; 3) high-BMI control women; and 4) low-BMI
      control women. The data were reanalyzed with the BMI cutoff value of 30 kg/m2 to
      corroborate the findings in obese and non-obese patients. Intervention(s): Blood
      samples were taken. Main Outcome Measure(s): LH, FSH, insulin, T, androstenedione
      (A4), DHEA, DHEAS, and glucose levels were determined. Homeostatic model
      assessment was calculated. Pelvic and abdominal ultrasound for ovarian morphology
      and adipose tissue, respectively, were performed. Results: Obese PCOS patients
      presented significantly more insulin resistance than non-obese PCOS patients. The
      LH levels and LH/FSH ratio were significantly higher in low-BMI than in high-BMI
      PCOS patients. The A4 and DHEAS levels were significantly higher in non-obese
      than in obese PCOS patients. A significant correlation between LH and A4 in non
      obese PCOS patients was observed. The frequency of hyperandrogenism by increased
      A4, and DHEA along with DHEAS was significantly higher in low-BMI PCOS patients
      compared to high-BMI PCOS patients. Some findings observed with the BMI cutoff
      value of 27 kg/m2 changed with the cutoff value of 30 kg/m2. Conclusions: Low BMI
      more than high BMI is associated with increased LH, high A4, DHEA and DHEAS
      levels in PCOS patients. The BMI cutoff value of 27 kg/m2 classified better than
      30 kg/m2 for hormonal and metabolic characteristics.

PMID- 25565294
TI  - Comparison of burn sizes resulting from photocoagulation using a transpupillary
      laser and an endolaser.

PMID- 25565295
TI  - Building of a composite virtual slide from contiguous tissue samples.
AB  - BACKGROUND: Currently available microscope slide scanners produce whole slide
      images at various resolutions from histological sections. Nevertheless,
      acquisition area and so visualization of large tissue samples are limited by the
      standardized size of glass slides, used daily in pathology departments. The
      proposed solution has been developed to build composite virtual slides from
      images of large tumor fragments. MATERIALS AND METHODS: Images of HES or
      immunostained histological sections of carefully labeled fragments from a
      representative slice of breast carcinoma were acquired with a digital slide
      scanner at a magnification of 20*. The tiling program involves three steps: the
      straightening of tissue fragment images using polynomial interpolation method,
      and the building and assembling of strips of contiguous tissue sample whole slide
      images in * and y directions. The final image is saved in a pyramidal BigTiff
      file format. The program has been tested on several tumor slices. A correlation
      quality control has been done on five images artificially cut. RESULTS: Sixty
      tumor slices from twenty surgical specimens, cut into two to twenty six pieces,
      were reconstructed. A median of 98.71% is obtained by computing the correlation
      coefficients between native and reconstructed images for quality control.
      CONCLUSIONS: The proposed method is efficient and able to adapt itself to daily
      work conditions of classical pathology laboratories.

PMID- 25565297
TI  - Experimental measurement-device-independent verification of quantum steering.
AB  - Bell non-locality between distant quantum systems--that is, joint correlations
      which violate a Bell inequality--can be verified without trusting the measurement
      devices used, nor those performing the measurements. This leads to
      unconditionally secure protocols for quantum information tasks such as
      cryptographic key distribution. However, complete verification of Bell non
      locality requires high detection efficiencies, and is not robust to typical
      transmission losses over long distances. In contrast, quantum or Einstein
      Podolsky-Rosen steering, a weaker form of quantum correlation, can be verified
      for arbitrarily low detection efficiencies and high losses. The cost is that
      current steering-verification protocols require complete trust in one of the
      measurement devices and its operator, allowing only one-sided secure key
      distribution. Here we present measurement-device-independent steering protocols
      that remove this need for trust, even when Bell non-locality is not present. We
      experimentally demonstrate this principle for singlet states and states that do
      not violate a Bell inequality.

PMID- 25565298
TI  - Highly sensitive method for specific, brief, and economical detection of
      glycoproteins in sodium dodecyl sulfate-polyacrylamide gel electrophoresis by the
      synthesis of a new hydrazide derivative.
AB  - A new hydrazide derivative was synthesized and used for the first time as a
      specific, brief, and economical probe to selectively visualize glycoproteins in 1
      D and 2-D sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      with high sensitivity. The detection limit of the newly developed staining method
      is 2- and 4-fold higher than that of the widely used Pro-Q Emerald 300 and 488
      stains, respectively. 

PMID- 25565296
TI  - Saireito (TJ-114), a Japanese traditional herbal medicine, reduces 5-fluorouracil
      induced intestinal mucositis in mice by inhibiting cytokine-mediated apoptosis in
      intestinal crypt cells.
AB  - Clinical chemotherapy frequently causes intestinal mucositis as a side effect,
      which is accompanied by severe diarrhea. We recently showed that the cytokine
      mediated apoptotic pathway might be important for the development of intestinal
      mucositis induced by 5-fluorouracil (5-FU). Saireito, the traditional Japanese
      herbal (Kampo) medicine, is widely used to treat diarrhea and various
      inflammatory diseases in Japan. In the present study, we investigated the effect
      of saireito on 5-FU-induced intestinal mucositis in mice, especially in relation
      to apoptosis in the intestinal crypt. Male C57BL/6 mice were given 5-FU (50
      mg/kg), i.p. once daily for 6 days. Intestinal mucositis was evaluated
      histochemically. Saireito (100-1000 mg/kg) was administered p.o. twice daily for
      6 days. Repeated 5-FU treatment caused severe intestinal mucositis including
      morphological damage, which was accompanied by body weight loss and diarrhea.
      Daily administration of saireito reduced the severity of intestinal mucositis in
      a dose-dependent manner. Body weight loss and diarrhea during 5-FU treatment were
      also significantly attenuated by saireito administration. The number of apoptotic
      and caspase-3-activated cells in the intestinal crypt was increased, and was
      accompanied by up-regulated tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-1beta mRNA within 24 h of the first 5-FU injection. However, all of these
      measures were significantly lower after saireito administration. These results
      suggest that saireito attenuates 5-FU-induced intestinal mucositis. This action
      may come from the reduction of apoptosis in the intestinal crypt via suppression
      of the up-regulation of inflammatory cytokines. Therefore, saireito may be
      clinically useful for the prevention of intestinal mucositis during cancer
      chemotherapy. 

PMID- 25565300
TI  - Internal coordinate density of state from molecular dynamics simulation.
AB  - The vibrational density of states (DoS), calculated from the Fourier transform of
      the velocity autocorrelation function, provides profound information regarding
      the structure and dynamic behavior of a system. However, it is often difficult to
      identify the exact vibrational mode associated with a specific frequency if the
      DoS is determined based on velocities in Cartesian coordinates. Here, the DoS is
      determined based on velocities in internal coordinates, calculated from Cartesian
      atomic velocities using a generalized Wilson's B-matrix. The DoS in internal
      coordinates allows for the correct detection of free dihedral rotations that may
      be mistaken as hindered rotation in Cartesian DoS. Furthermore, the pronounced
      enhancement of low frequency modes in Cartesian DoS for macromolecules should be
      attributed to the coupling of dihedral and angle motions. The internal DoS, thus
      deconvolutes the internal motions and provides fruitful insights to the dynamic
      behaviors of a system.

PMID- 25565299
TI  - Association of luteinizing hormone chorionic gonadotropin receptor gene
      polymorphism (rs2293275) with polycystic ovarian syndrome.
AB  - BACKGROUND: Polycystic ovaries and irregular menstruation/anovulation are
      important diagnostic criteria along with hyperandrogenism as per the Androgen
      Excess Society-2006 criteria for polycystic ovarian syndrome (PCOS). In the
      etiopathogenesis of PCOS, one of the candidate genes causing ovarian failure is
      the luteinizing hormone (LH) chorionic gonadotropin hormone receptor (LHCGR). Our
      aim was to study the association of LHCGR polymorphism (rs2293275) with PCOS in
      our study population. MATERIALS AND METHODS: Genetic case-control study from
      multiple gynecological centers from Hyderabad, a cosmopolitan city in South
      India. The study involved 204 women with PCOS and 204 healthy, sex-, and age
      matched controls. Anthropometric and biochemical profiles were taken in a well
      designed pro forma. Isolation of deoxyribonucleic acid (DNA) and genotype
      analysis were done for the entire study population using the polymerase chain
      reaction-restriction fragment length polymorphism method followed by 12%
      polyacrylamide gel electrophoresis. RESULTS: In this study, we have demonstrated
      an association between LHCGR (rs2293275) polymorphism and PCOS. The frequency of
      the G allele was 0.60 in PCOS and 0.49 in controls (odds ratio [OR] 1.531,
      confidence interval [CI] 1.16-2.01, and p-value=0.0026), which indicates that the
      G allele is associated with PCOS in our population. The GG genotype conferred a
      significant risk of developing PCOS (OR 3.36, CI 1.96-5.75, and p-value<0.0001).
      We found a significant association of the GG allele with body-mass index, waist
      to hip ratio, insulin resistance, LH, and LH/follicle-stimulating hormone (FSH)
      ratio in PCOS when compared with controls. The AA allele showed high basal FSH
      levels. CONCLUSIONS: This study suggests that LHCGR (rs2293275) polymorphism is
      associated with PCOS and could be used as a relevant molecular marker to identify
      women with the risk of developing PCOS in our population and may provide an
      understanding about the etiology of PCOS.

PMID- 25565301
TI  - Structural progression in clusters of ionized water, (H2O)n=1-5(+).
AB  - Ionized water clusters serve as a model of water-splitting chemistry for
      energetic purposes, as well as postradiolytic events in condensed-phase systems.
      Structures, properties, and relative energies are presented for oxidized water
      clusters, (H2O)n=1-5(+), using equation-of-motion coupled-cluster theory
      approaches. In small clusters, an ion-radical contact pair OH...H3O+ is known to
      form upon ionization. The transition from n = 4 to n = 5 molecules in the
      cluster, however, is found to demarcate a size regime in which a propensity for
      the ion and radical to separate exists. This trend is consistent with recent
      experimental vibrational analyses. Decomposition of the cluster energetics
      reveals that preferential solvation of the hydronium cation by water serves as
      the dominant driving force for this pair separation, which should persist in
      larger clusters and bulk water ionization.

PMID- 25565302
TI  - Patient blood management in cardiac surgery results in fewer transfusions and
      better outcome.
AB  - BACKGROUND: The aim of this study was to investigate the impact of the
      introduction of a patient blood management (PBM) program in cardiac surgery on
      transfusion incidence and outcome. STUDY DESIGN AND METHODS: Clinical and
      transfusion data were compared between the pre-PBM epoch (July 2006-March 2007)
      and the PBM epoch (April 2007-September 2012). RESULTS: There were a total of
      2662 patients analyzed, 387 in the pre-PBM and 2275 in the PBM epoch. Red blood
      cell (RBC) loss decreased from a mean (+/-SD) of 810 +/- 426 mL (median, 721 mL)
      to 605 +/- 369 mL (median, 552 mL; p < 0.001) and pretransfusion hemoglobin
      decreased from 7.2 +/- 1.4 to 6.6 +/- 1.2 g/dL (p < 0.001) in the pre-PBM versus
      the PBM epoch. In conjunction, this resulted in a reduction of the RBC
      transfusion rate from 39.3% to 20.8% (p < 0.001). Similar reductions were
      observed for the transfusion of fresh-frozen plasma (FFP; from 18.3% to 6.5%, p <
      0.001) and platelets (PLTs; from 17.8% to 9.8%, p < 0.001). Hospital mortality
      and cerebral vascular accident incidence remained unchanged in the PBM epoch.
      However, the incidence of postoperative kidney injury decreased in the PMB epoch
      (from 7.6% to 5.0%, p = 0.039), length of hospital stay decreased from 12.2 +/-
      9.6 days (median, 10 days) to 10.4 +/- 8.0 days (median, 8 days; p < 0.001), and
      total adjusted direct costs were reduced from $48,375 +/- $28,053 (median,
      $39,709) to $44,300 +/- $25,915 (median, $36,906; p < 0.001). CONCLUSIONS:
      Implementing meticulous surgical technique, a goal-directed coagulation
      algorithm, and a more restrictive transfusion threshold in combination resulted
      in a substantial decrease in RBC, FFP, and PLT transfusions; less kidney injury;
      a shorter length of hospital stay; and lower total direct costs.

PMID- 25565303
TI  - Using the sessile drop geometry to measure fluid and elastic block copolymer
      interfaces.
AB  - There is considerable interest in the fabrication and mechanics of soft spheres
      and capsules because of their use in a large number of applications ranging from
      targeted drug delivery to cosmetically active agents. Many systems, such as lipid
      and block copolymer vesicles, are already finding considerable industrial use
      where the performance of soft spheres depends intimately on their mechanics. New
      advanced features such as fast cargo delivery can be realized only if they fit
      into the existing mechanical niche of the system in question. Here we present a
      model system to demonstrate how a capsule structure can be fundamentally changed
      while maintaining its overall mechanical response as well as a simple, universal
      method to measure the resulting capsule material properties. Specifically, we use
      confocal microscopy to adapt the sessile drop geometry to a measurement of the
      static properties of an ensemble of polystyrene-b-poly(ethylene oxide) (PS-PEO)
      stabilized oil droplets. We then synthesize a polystyrene-b-poly(acrylic acid)-b
      polystyrene (PS-PAA-PS) elastic-shell-coated emulsion drop that shows an
      identical deformation to the fluidlike PS-PEO droplets. Both systems, in sessile
      geometry, can be related to their basic material properties through appropriate
      modeling. We find that the elastic shell is dominated by its surface tension,
      easily enabling it to match the static response of a purely fluid drop. 

PMID- 25565304
TI  - Economic Burden of Psoriasis in the United States: A Systematic Review.
AB  - IMPORTANCE: The total cost of psoriasis in the United States is unknown. Defining
      the US economic burden of psoriasis is needed because it provides the foundation
      for research, advocacy, and educational efforts. OBJECTIVE: To determine the US
      economic burden of psoriasis from a societal perspective. EVIDENCE REVIEW: PubMed
      and MEDLINE databases were searched between January 1, 2008, and September 20,
      2013, for economic investigations on the direct, indirect, intangible, and
      comorbidity costs of adult psoriasis in the United States. The base year costs
      were adjusted to 2013 US dollars using the Consumer Price Index for All Urban
      Consumers and multiplied by the estimated number of US patients with psoriasis in
      2013 to determine the 2013 psoriasis cost burden. FINDINGS: Among 100 identified
      articles, 22 studies were included in the systematic review. The direct psoriasis
      costs ranged from $51.7 billion to $63.2 billion, the indirect costs ranged from
      $23.9 billion to $35.4 billion, and medical comorbidities were estimated to
      contribute $36.4 billion annually in 2013 US dollars. Patients with psoriasis
      would pay a lifetime cost of $11,498 for relief of physical symptoms and
      emotional health; however, intangible cost data are limited. The annual US cost
      of psoriasis amounted to approximately $112 billion in 2013. CONCLUSIONS AND
      RELEVANCE: The economic burden of psoriasis is substantial and significant in the
      United States.

PMID- 25565305
TI  - Schooling duration rather than chronological age predicts working memory between
      6 and 7 years: Memory Maestros Study.
AB  - OBJECTIVE: Low working memory (WM) is strongly linked with poor academic
      outcomes. WM capacity increases across childhood but how exposure to school is
      associated with WM development is not known. We aimed to determine extent to
      which chronological age and schooling duration are associated with WM at the
      population level. METHODS: In 2012, children in Grade 1 (the second year of
      formal schooling in Victoria, Australia) from 44 schools in metropolitan
      Melbourne were recruited. Assessments occurred over the entire school year, with
      schools quasi-randomly allocated to one of the 4 school terms. WM (primary
      outcome) was measured using 2 subtests from the computerized Automated Working
      Memory Assessment: Backwards Digit Recall (verbal) and Mister X (visuospatial).
      Linear regression was used to examine relationships of WM with time in school and
      age. RESULTS: Of the 1765 who provided consent, 1727 children (97.9%) had WM
      assessed throughout the 2012 school year. WM scores became steadily higher over
      the course of the year. Thus, scores were .77 and .53 SDs higher in Term 4 than
      Term 1 for verbal and visuospatial WM, respectively (p values for trend for both
      scores <.001); conclusions were unchanged when adjusted for age and potential
      confounders. Conversely, age associations attenuated fully once adjusted for
      school duration. CONCLUSIONS: Our results demonstrate, for the first time, that
      the developmental increases in WM are strongly associated with time spent in the
      classroom, above and beyond chronological age.

PMID- 25565306
TI  - Prosthesis loading after temporomandibular joint replacement surgery: a
      musculoskeletal modeling study.
AB  - One of the most widely reported complications associated with temporomandibular
      joint (TMJ) prosthetic total joint replacement (TJR) surgery is condylar
      component screw loosening and instability. The objective of this study was to
      develop a musculoskeletal model of the human jaw to assess the influence of
      prosthetic condylar component orientation and screw placement on condylar
      component loading during mastication. A three-dimensional model of the jaw
      comprising the maxilla, mandible, masticatory muscles, articular cartilage, and
      articular disks was developed. Simulations of mastication and a maximum force
      bite were performed for the natural TMJ and the TMJ after prosthetic TJR surgery,
      including cases for mastication where the condylar component was rotated
      anteriorly by 0 deg, 5 deg, 10 deg, and 15 deg. Three clinically significant
      screw configurations were investigated: a complete, posterior, and minimal
      posterior screw (MPS) configuration. Increases in condylar anterior rotation led
      to an increase in prosthetic condylar component contact stresses and substantial
      increases in condylar component screw stresses. The use of more screws in
      condylar fixation reduced screw stress magnitudes and maximum condylar component
      stresses. Screws placed superiorly experienced higher stresses than those of all
      other condylar fixation screws. The results of the present study have important
      implication for the way in which prosthetic components are placed during TMJ
      prosthetic TJR surgery. 

PMID- 25565308
TI  - Genetic homogeneity but IgG subclass-dependent clinical variability of alloimmune
      membranous nephropathy with anti-neutral endopeptidase antibodies.
AB  - Alloimmune antenatal membranous nephropathy (MN) during pregnancy results from
      antibodies produced by a neutral endopeptidase (NEP)-deficient mother. Here we
      report two recent cases that provide clues to the severity of renal disease.
      Mothers of the two children had circulating antibodies against NEP showing the
      characteristic species-dependent pattern by immunofluorescence on kidney slices.
      A German mother produced predominantly anti-NEP IgG4 accompanied by a low amount
      of IgG1. Her child recovered renal function within a few weeks. In sharp
      contrast, an Italian mother mainly produced complement-fixing anti-NEP IgG1,
      which also inhibits NEP enzymatic activity, whereas anti-NEP IgG4 has a weak
      inhibitory potency. Her child was dialyzed for several weeks. A kidney biopsy
      performed at 12 days of age showed MN, ischemic glomeruli, and arteriolar and
      tubular lesions. A second biopsy performed at 12 weeks of age showed aggravation
      with an increased number of collapsed capillary tufts. Both mothers were
      homozygous for the truncating deletion mutation 466delC and were thus NEP
      deficient. The 466delC mutation, identified in three previously described
      families, suggests a founder effect. Because of the potential severity of
      alloimmune antenatal MN, it is essential to identify families at risk by the
      detection of anti-NEP antibodies and NEP antigen in urine. On the basis of the
      five families identified to date, we propose an algorithm for the diagnosis of
      the disease and the prevention of complications. 

PMID- 25565307
TI  - Increased plasma catalytic iron in patients may mediate acute kidney injury and
      death following cardiac surgery.
AB  - Catalytic iron, the chemical form of iron capable of participating in redox
      cycling, is a key mediator of acute kidney injury (AKI) in multiple animal
      models, but its role in human AKI has not been studied. Here we tested in a
      prospective cohort of 250 patients undergoing cardiac surgery whether plasma
      catalytic iron levels are elevated and associated with the composite outcome of
      AKI requiring renal replacement therapy or in-hospital mortality. Plasma
      catalytic iron, free hemoglobin, and other iron parameters were measured
      preoperatively, at the end of cardiopulmonary bypass, and on postoperative days 1
      and 3. Plasma catalytic iron levels, but not other iron parameters, rose
      significantly at the end of cardiopulmonary bypass and were directly associated
      with bypass time and number of packed red blood cell transfusions. In
      multivariate analyses adjusting for age and preoperative eGFR, patients in the
      highest compared with the lowest quartile of catalytic iron on postoperative day
      1 had a 6.71 greater odds of experiencing the primary outcome, and also had
      greater odds of AKI, hospital mortality, and postoperative myocardial injury.
      Thus, our data are consistent with and expand on findings from animal models
      demonstrating a pathologic role of catalytic iron in mediating adverse
      postoperative outcomes. Interventions aimed at reducing plasma catalytic iron
      levels as a strategy for preventing AKI in humans are warranted. 

PMID- 25565309
TI  - Tubulointerstitial nephritis is a dominant feature of hereditary apolipoprotein A
      I amyloidosis.
AB  - Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and
      is encoded by the APOA1 gene. Several APOA1 mutations have been found, either
      affecting the lecithin:cholesterol acyltransferase activity, determining familial
      HDL deficiency, or resulting in amyloid formation with prevalent deposits in the
      kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients
      with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of
      253 carriers belonging to 50 families from Brescia, Italy. A total of 219
      mutation carriers underwent clinical, laboratory, and instrumental tests. Of
      these, 62% had renal, hepatic, and testicular disease; 38% were asymptomatic. The
      disease showed an age-dependent penetrance. Tubulointerstitial nephritis was
      diagnosed in 49% of the carriers, 13% of whom progressed to kidney failure
      requiring dialysis. Hepatic involvement with elevation of cholestasis indices was
      diagnosed in 30% of the carriers, 38% of whom developed portal hypertension.
      Impaired spermatogenesis and hypogonadism was found in 68% of male carriers. The
      cholesterol levels were lower than normal in 80% of the mutation carriers. Thus,
      tubulointerstitial nephritis was highly prevalent in this large series of
      patients with Leu75Pro apoA-I amyloidosis. Persistent elevation of alkaline
      phosphatase, reduced HDL cholesterol plasma levels, and hypogonadism in men are
      key diagnostic features of this form of amyloidosis. 

PMID- 25565310
TI  - CD11b is protective in complement-mediated immune complex glomerulonephritis.
AB  - In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do
      not develop glomerulonephritis unless complement factor H (CfH) is absent,
      indicating the relevance of complement regulation. Complement receptor 3 (CD11b)
      and Fcgamma receptors on leukocytes, and CfH on platelets, can bind immune
      complexes. Here we induced immune complex-mediated glomerulonephritis in CfH(-/-)
      mice chimeric for wild-type, CfH(-/-), CD11b(-/-), or FcRgamma(-/-) bone marrow
      stem cells. Glomerulonephritis was worse in CD11b(-/-) chimeras compared with all
      others, whereas disease in FcRgamma(-/-) and wild-type chimeras was comparable.
      Disease tracked strongly with humoral immune responses, but not glomerular immune
      complex deposits. Interstitial inflammation with M1 macrophages strongly
      correlated with glomerulonephritis scores. CD11b(-/-) chimeras had significantly
      more M1 macrophages and CD4(+) T cells. The renal dendritic cell populations
      originating from bone marrow-derived CD11c(+) cells were similar in all
      experimental groups. CD11b(+) cells bearing colony-stimulating factor 1 receptor
      were present in kidneys, including CD11b(-/-) chimeras; these cells correlated
      negatively with glomerulonephritis scores. Thus, experimental immune complex
      mediated glomerulonephritis is associated with accumulation of M1 macrophages and
      CD4(+) T cells in kidneys and functional renal insufficiency. Hence, CD11b on
      mononuclear cells is instrumental in generating an anti-inflammatory response in
      the inflamed kidney. 

PMID- 25565311
TI  - No development of hypertension in the hyperuricemic liver-Glut9 knockout mouse.
AB  - Urate is the metabolic end point of purines in humans. Although supra
      physiological plasma urate levels are associated with obesity, insulin
      resistance, dyslipidemia, and hypertension, a causative role is debated. We
      previously established a mouse model of hyperuricemia by liver-specific deletion
      of Glut9, a urate transporter that provides urate to the hepatocyte enzyme
      uricase. These LG9 knockout mice show mild hyperuricemia (120 MUmol/l), which can
      be further increased by the urate precursor inosine. Here, we explored the role
      of progressive hyperuricemia on the cardiovascular function. Arterial blood
      pressure and heart rate were periodically measured by telemetry over 6 months in
      LG9 knockout mice supplemented with incremental amounts of inosine in a normal
      chow diet. This long-term inosine treatment elicited a progressive increase in
      uricemia up to 300 MUmol/l; however, it did not modify heart rate or mean
      arterial blood pressure in LG9 knockout compared with control mice. Inosine
      treatment did not alter cardiac morphology or function measured by ultrasound
      echocardiography. However, it did induce mild renal dysfunction as revealed by
      higher plasma creatinine levels, lower glomerular filtration rate, and
      histological signs of chronic inflammation and fibrosis. Thus, in LG9 knockout
      mice, inosine-induced hyperuricemia was not associated with hypertension despite
      partial renal deficiency. This does not support a direct role of urate in the
      control of blood pressure. 

PMID- 25565312
TI  - Restricted specificity of peripheral alloreactive memory B cells in HLA
      sensitized patients awaiting a kidney transplant.
AB  - The contribution of memory B cells in alloreactive humoral responses remains
      poorly understood. Here we tested the presence of circulating alloreactive memory
      B cells in 69 patients with end-stage renal disease under renal replacement
      therapy, using an in vitro memory B cell-stimulation assay combined with
      identification of IgG human leukocyte antigen (HLA) antibodies in culture
      supernatant. HLA antibody-producing memory B cells were evidenced only in
      patients carrying serum HLA antibodies following multiple classical HLA
      immunizing events. In patients with a previous renal allograft, alloreactive
      memory B cells could be detected ranging from 6 to 32 years (mean 13.2 years)
      after transplantation. HLA antibodies produced by memory B cells were also
      detected in the corresponding sera and showed a restricted reactivity, targeting
      only a few epitopes shared by several HLA antigens. In contrast, serum HLA
      antibodies, not associated with the detection of specific memory B cells, showed
      a broader pattern of specificities. Thus, expansion and survival of alloreactive
      memory B cells is alloantigen driven, and their frequency is related to the
      'strength' of HLA immunization. 

PMID- 25565314
TI  - Iron(III)-bearing clay minerals enhance bioreduction of nitrobenzene by
      Shewanella putrefaciens CN32.
AB  - Iron-bearing clay minerals are ubiquitous in the environment, and the clay
      Fe(II)/Fe(III) redox couple plays important roles in abiotic reduction of several
      classes of environmental contaminants. We investigated the role of Fe-bearing
      clay minerals on the bioreduction of nitrobenzene. In experiments with Shewanella
      putrefaciens CN32 and excess electron donor, we found that the Fe-bearing clay
      minerals montmorillonite SWy-2 and nontronite NAu-2 enhanced nitrobenzene
      bioreduction. On short time scales (<50 h), nitrobenzene reduction was primarily
      biologically driven, but at later time points, nitrobenzene reduction by
      biologically formed structural Fe(II) in the clay minerals became increasingly
      important. We found that chemically reduced (dithionite) iron-bearing clay
      minerals reduced nitrobenzene more rapidly than biologically reduced iron-bearing
      clay minerals despite the minerals having similar structural Fe(II)
      concentrations. We also found that chemically reduced NAu-2 reduced nitrobenzene
      faster as compared to chemically reduced SWy-2. The different reactivity of SWy-2
      versus NAu-2 toward nitrobenzene was caused by different forms of structural clay
      Fe(II) in the clay minerals and different reduction potentials (Eh) of the clay
      minerals. Because most contaminated aquifers become reduced via biological
      activity, the reactivity of biogenic clay-Fe(II) toward reducible contaminants is
      particularly important.

PMID- 25565315
TI  - Base-promoted oxidative C-H functionalization of alpha-amino carbonyl compounds
      under mild metal-free conditions: using molecular oxygen as the oxidant.
AB  - A base-mediated aerobic oxidation of the C-H bond adjacent to the N-atom of a
      secondary amine to form an imine intermediate under mild metal-free basic
      conditions has been developed. Accordingly, this new strategy has been
      successfully applied to the synthesis of various di-, tri-, and tetra-substituted
      alpha-aminocyclopentenones through a tandem aerobic oxidative [4 + 1]
      carbocyclization reaction of N-aryl alpha'-amino-alpha,beta-unsaturated ketones
      as C4 1,4-dielectrophiles with active methylenes, including ethyl
      isocyanoacetate, nitroalkanes, and ethyl cyanoacetate, as C1 components. 

PMID- 25565316
TI  - Macroscopic barotrauma caused by stiff and soft-tipped airway exchange catheters:
      an in vitro case series.
AB  - BACKGROUND: Many airway management guidelines include the use of airway exchange
      catheters (AECs). There are reports, however, of harm from their use, from both
      malpositioning and in particular from the administration of oxygen via an AEC
      leading to barotrauma. METHODS: We used an in vitro pig lung model to investigate
      the safety of administering oxygen at 4 different flow rates from a high-pressure
      source via 2 different AECs: a standard catheter and a soft-tipped catheter.
      Experiments were performed with the catheters positioned either above the carina
      or below it at the first point of resistance to advancement (hold-up). The
      experiments were then repeated to produce a series of 32 cases. RESULTS: With an
      AEC positioned above the carina, we did not observe macroscopic lung damage after
      the administration of oxygen. The administration of oxygen through an AEC
      positioned below the carina resulted in macroscopic barotrauma regardless of the
      rate of oxygen delivery. Increasing speed of oxygen flow led to faster and more
      extensive damage. Use of an "injector" at 2.5 or 4 bar led to instantaneous
      macroscopic lung damage and advancement of the AEC through the lung tissue. Our
      observations were the same when both types of AECs were used. CONCLUSIONS: Our
      results are consistent with reports of harm during the use of AECs and
      demonstrate the risk of administering oxygen through these devices when they are
      positioned below the carina. An indicator, ideally made on an AEC at the time of
      manufacture and designed to lie at the same level as the teeth, may be useful in
      preventing the insertion of that AEC beyond the level of the carina and improve
      the safety of using such devices.

PMID- 25565317
TI  - Extracorporeal membrane oxygenation induces short-term loss of high-molecular
      weight von Willebrand factor multimers.
AB  - BACKGROUND: High-molecular-weight (HMW) von Willebrand factor (vWF) multimers are
      crucial for primary hemostasis. Increased shear stress from ventricular assist
      devices can provoke premature degradation of HMW vWF multimers. Whether similar
      loss of vWF multimers occurs during extracorporeal membrane oxygenation (ECMO) is
      not clear. METHODS: We conducted a prospective observational study in a clinical
      cohort of patients who required ECMO for intractable cardiac and/or respiratory
      failure. The primary end point was the quantity and quality of HMW vWF multimer
      bands before, during, and after ECMO support. To investigate further changes in
      primary hemostasis, we also measured vWF antigen activity (vWF:Ag), vWF
      ristocetin cofactor activity (vWF:RCo), and factor VIII in 38 patients who
      required ECMO support before initiation of ECMO (baseline), after 24 and 48 hours
      on ECMO, and 24 hours after termination of ECMO therapy. RESULTS: Compared with
      baseline, vWF:Ag and vWF:RCo decreased after 24 hours of ECMO (mean +/- SD,
      vWF:Ag, 307% +/- 152% to 261% +/- 138%, P = 0.002; vWF:RCo 282% +/- 145% to 157%
      +/- 103%, P < 0.0001) and remained lower during ongoing support (vWF:Ag 265% +/-
      128%, P = 0.025; vWF:RCo 163% +/- 94%, P < 0.0001). After termination of ECMO,
      vWF:Ag was greater than baseline (359% +/- 131%, P = 0.004) and vWF:RCo was
      similar to baseline levels (338% +/- 142%, P = 0.046). Compared with baseline,
      the calculated vWF:RCo/vWF:Ag ratio decreased after 24 hours on support (0.96 +/-
      0.23 to 0.61 +/- 0.17, P <= 0.0001) and remained lower during 48 hours on ECMO
      (0.63 +/- 0.18, P <= 0.0001). After termination of ECMO support (0.94 +/- 0.19, P
      = 0.437), values rapidly returned to baseline. The number of HMW vWF multimers
      (n) decreased from baseline after 24 hours on ECMO (21 +/- 1.4 to 14 +/- 1.8, P
      <= 0.0001) and after 48 hours on ECMO (15 +/- 2.1, P <= 0.0001). Twenty-four
      hours after termination of ECMO support, HMW vWF multimeric pattern had returned
      to baseline values (21 +/- 1.8, P = 0.551). CONCLUSIONS: Loss of HMW vWF multimer
      bands occurred in patients undergoing ECMO support and resolved after the
      termination of ECMO. Although not detectable with coagulation screening tests, a
      vWF:RCo/vWF:Ag ratio <0.7 during ECMO was highly indicative for loss of HMW vWF
      multimers. Our findings may at least in part explain increased bleeding tendency
      during ECMO therapy. Administration of vWF concentrates may support restoration
      of primary hemostasis in patients with relevant bleeding during ECMO support.

PMID- 25565318
TI  - Crystalloids versus colloids: exploring differences in fluid requirements by
      systematic review and meta-regression.
AB  - BACKGROUND: Positive fluid balance has been associated with worse outcomes, and
      knowledge of differences in the amounts of different types of fluid needed to
      achieve the same end points may have important clinical implications. Large
      molecules persist longer in the blood vessels than smaller molecules, such that
      less IV colloid may be needed to achieve similar hemodynamic end points compared
      with crystalloid. Recent clinical data have, however, challenged this
      physiological concept, with investigators reporting lower-than-expected
      crystalloid/colloid ratios in various populations. METHODS: We performed a
      systematic search in MEDLINE, EMBASE, and CENTRAL up to December 18, 2013, to
      retrieve all studies comparing (any) crystalloid with (any) colloid in all types
      of patients. The crystalloid/colloid ratio was calculated for each study.
      Descriptive analysis was performed for all studies, and a meta-analysis was
      performed in those studies reporting full data (in terms of means and standard
      deviations) of infused fluid volumes. Studies were grouped according to study and
      population characteristics. A meta-regression analysis was then performed to
      evaluate some of the possible reasons for differences in crystalloid/colloid
      ratios across studies. RESULTS: From 976 studies, 48 were retained for the final
      analysis; 24 of the studies had sufficient data for meta-analysis. The
      crystalloid/colloid ratio across all the studies included in the meta-analysis
      was 1.5 (95% confidence interval, 1.36-1.65) with marked heterogeneity among
      studies (I = 94%). From the meta-regression analysis, decade of publication
      across all publications (P = 0.001) and concentration (tonicity) in the subgroup
      of albumin studies (P = 0.001) were associated with the administered
      crystalloid/colloid ratio. The reduction in heterogeneity among studies for all
      publications in the meta-regression was minimal, with the maximal decrease
      obtained when decade of publication was considered (R = 12%). CONCLUSIONS:
      Greater fluid volumes are required to meet the same targets with crystalloids
      than with colloids, with an estimated ratio of 1.5 (1.36-1.65), but there is
      marked heterogeneity among studies. The crystalloid/colloid ratio seems to have
      decreased over the years, and differences in ratios are correlated with the
      concentration of albumin solutions; however, the main reasons behind the high
      heterogeneity among studies remain unclear.

PMID- 25565313
TI  - p47(phox) contributes to albuminuria and kidney fibrosis in mice.
AB  - Reactive oxygen species (ROS) have an important pathogenic role in the
      development of many diseases, including kidney disease. Major ROS generators in
      the glomerulus of the kidney are the p47(phox)-containing NAPDH oxidases NOX1 and
      NOX2. The cytosolic p47(phox) subunit is a key regulator of the assembly and
      function of NOX1 and NOX2 and its expression and phosphorylation are upregulated
      in the course of renal injury, and have been shown to exacerbate diabetic
      nephropathy. However, its role in nondiabetic-mediated glomerular injury is
      unclear. To address this, we subjected p47(phox)-null mice to either adriamycin
      mediated or partial renal ablation-mediated glomerular injury. Deletion of
      p47(phox) protected the mice from albuminuria and glomerulosclerosis in both
      injury models. Integrin alpha1-null mice develop more severe glomerulosclerosis
      compared with wild-type mice in response to glomerular injury mainly due to
      increased production of ROS. Interestingly, the protective effects of p47(phox)
      knockout were more profound in p47(phox)/integrin alpha1 double knockout mice. In
      vitro analysis of primary mesangial cells showed that deletion of p47(phox) led
      to reduced basal levels of superoxide and collagen IV production. Thus, p47(phox)
      dependent NADPH oxidases are a major glomerular source of ROS, contribute to
      kidney injury, and are potential targets for antioxidant therapy in fibrotic
      disease. 

PMID- 25565319
TI  - Rescue ventilation through a small-bore transtracheal cannula in severe hypoxic
      pigs using expiratory ventilation assistance.
AB  - BACKGROUND: Suction-generated expiratory ventilation assistance (EVA) has been
      proposed as a way to facilitate bidirectional ventilation through a small-bore
      transtracheal cannula (TC). In this study, we investigated the efficiency of
      ventilation with EVA for restoring oxygenation and ventilation in a pig model of
      acute hypoxia. METHODS: Six pigs (61-76 kg) were anesthetized and ventilated
      (intermittent positive pressure ventilation) via a cuffed endotracheal tube
      (ETT). Monitoring lines were placed, and a 75-mm long, 2-mm inner diameter TC was
      inserted. After the baseline recordings, the ventilator was disconnected. After 2
      minutes of apnea, reoxygenation with EVA was initiated through the TC and
      continued for 15 minutes with the ETT occluded. In the second part of the study,
      the experiment was repeated with the ETT either partially obstructed or left
      open. Airway pressures and hemodynamic data were recorded, and arterial blood
      gases were measured. Descriptive statistical analysis was performed. RESULTS:
      With a completely or partially obstructed upper airway, ventilation with EVA
      restored oxygenation to baseline levels in all animals within 20 seconds. In a
      completely obstructed airway, PaCO2 remained stable for 15 minutes. At lesser
      degrees of airway obstruction, the time to reoxygenation was delayed. Efficacy
      probably was limited when the airway was completely unobstructed, with 2 of 6
      animals having a PaO2 <85 mm Hg even after 15 minutes of ventilation with EVA and
      a mean PaCO2 increased up to 90 mm Hg. CONCLUSIONS: In severe hypoxic pigs,
      ventilation with EVA restored oxygenation quickly in case of a completely or
      partially obstructed upper airway. Reoxygenation and ventilation were less
      efficient when the upper airway was completely unobstructed.

PMID- 25565320
TI  - Sham procedure inadequate.

PMID- 25565322
TI  - Twelve-Month Follow-Up of a Randomized Trial Assessing Cooled Radiofrequency
      Denervation as a Treatment for Sacroiliac Region Pain.
AB  - OBJECTIVE: The objective of this study was to report the long-term outcomes of
      cooled radiofrequency (CRF) lateral branch neurotomy (LBN) as a treatment for
      sacroiliac (SI) region pain. Whereas the 1-, 3-, 6-, and 9-month outcomes of this
      procedure compared to sham treatment were previously reported, this current
      report shows the 12-month outcomes of CRF/LBN treatment for SI region pain.
      DESIGN: This study originally included 51 subjects who were randomized 2:1 to
      receive CRF/LBN treatment or a sham intervention, respectively, for SI region
      pain. Subjects and assessors were blinded for 3 months. At that time, sham
      participants were permitted to receive CRF/LBN, designated as "crossover" study
      subjects, and followed for 6 additional months. For the purpose of this
      evaluation, the original CRF/LBN-treated study subjects were followed for a total
      of 12 months. Study participants were 18 to 88 years of age and had chronic
      (symptomatic for >6 months) axial back pain. All subjects were qualified for
      study inclusion following positive responses to dual lateral branch blocks.
      Lateral branch neurotomy was performed by CRF to ablate the S1 to S3 lateral
      branches and the L5 dorsal ramus. Pain was measured by a numerical rating scale
      (NRS) and Short Form 36-bodily pain (SF36-BP) scores. The Oswestry disability
      index and Short Form 36-physical functioning (SF36-PF) assessment each served to
      evaluate subject disability. Treatment successes ("responders") in the originally
      treated CRF/LBN group at 12 months, and in the crossover group at 6 months, were
      also determined. RESULTS: In the original CRF/LBN treatment group, 12-month
      outcomes compared to baseline were favorable, with a mean 2.7 point drop in the
      NRS score, a 13.9 decrease in the ODI, and a 15.8 increase in SF-36BP. In the
      crossover study group, 6-month outcomes were also favorable, with a mean NRS
      score decrease of 2.5 points, a reduction in ODI of 8.8, and an increase in SF36
      BP of 11.9. CONCLUSIONS: These favorable 12-month results illustrate the
      durability of effective CRF/LBN-mediated treatment of SI region pain for selected
      patients. Furthermore, successful CRF/LBN treatments in unblinded crossover study
      subjects demonstrate the unlikelihood that such positive outcomes are
      attributable to a "placebo" effect, and suggest that CRF/LBN is an effective
      therapeutic option for alleviating pain, and improving physical function and
      quality of life, with few complications.

PMID- 25565323
TI  - Application of the estrogen threshold hypothesis to the physiologic
      hypoestrogenemia of lactation.
AB  - OBJECTIVE: This study determined the impact of breastfeeding on hypoestrogenic
      symptoms among women in the postpartum period and correlated these findings with
      the Estrogen Threshold Hypothesis, which postulates that the hypoestrogenic
      symptoms experienced are related to circulating estrogen levels. STUDY DESIGN:
      Using a survey instrument that combined previously validated assessments of
      postpartum mood changes and menopausal symptoms, women were evaluated in the
      immediate postpartum period, prior to hospital discharge, and at 3 and 6 weeks
      postpartum. Each time period was analyzed independently, in a cross-sectional
      design, where women were categorized as "breastfeeding" or "bottle feeding."
      RESULTS: Of 236 women recruited, 171 (72.5%) intended to breastfeed, and 62
      (26.3%) intended to bottle feed. At both the 3- and 6-week postpartum
      evaluations, a similar percentage of women in the breastfeeding and bottle
      feeding groups reported hot flashes. However, breastfeeding women were more
      likely to report vaginal dryness than those who did not breastfeed: 20/150
      (13.3%) versus 3/80 (3.8%) at 3 weeks, p<0.05; 25/143 (17.5%) versus 2/87 (2.3%)
      at 6 weeks, p<0.001. CONCLUSIONS: The Estrogen Threshold Hypothesis accurately
      predicts the findings of increased reported vaginal dryness but not hot flashes
      during lactation.

PMID- 25565324
TI  - Anti-citrullinated peptide antibodies in Sudanese patients with Leishmania
      donovani infection exhibit reactivity not dependent on citrullination.
AB  - African patients with Leishmania donovani infections have signs of strong
      systemic inflammation and high levels of circulating immune complexes (IC) and
      rheumatoid factor (RF), all serologic markers of rheumatic disease. As
      inflammation in general is associated with citrullination, we sought to
      investigate ACPA responses in Sudanese Leishmania patients. Serum samples were
      collected from Sudanese patients with visceral leishmaniasis (VL) and post-kala
      azar dermal leishmaniasis (PKDL) as well as from ACPA-positive Sudanese
      rheumatoid arthritis patients and compared to healthy Sudanese controls. Levels
      of circulating C1q-binding IC and anticyclic citrullinated peptide 2(CCP2) were
      investigated using ELISA, and RF was measured with nephelometry. C1q adsorption
      was carried out to investigate anti-CCP2 content in IC. Citrulline specificity
      was evaluated with control plates with cyclic arginine-containing control
      peptides. Leishmania-infected patients had elevated levels of RF and circulating
      IC but also a significant increase in anti-CCP2 (12%) as compared to healthy
      controls. Anti-CCP2-positive Leishmania patients displayed lower anti-CCP2 levels
      than Sudanese patients with rheumatoid arthritis (RA), and anti-CCP2 levels in
      Leishmania patients showed a continuum not resembling the dichotomous pattern
      seen in patients with RA. Whereas the anti-CCP reactivity of Sudanese RA sera was
      strictly citrulline dependent, anti-CCP2-positive Leishmania sera reacted equally
      well with ELISA plates containing arginine control peptides. There was a strong
      correlation between anti-CCP2 and circulating IC among the Leishmania patients,
      but IC depletion only marginally diminished anti-CCP2 levels. Our findings stress
      the importance to interpret a positive CCP test carefully when evaluated in non
      rheumatic conditions associated with macrophage activation. 

PMID- 25565321
TI  - Pivotal and distinct role for Plasmodium actin capping protein alpha during blood
      infection of the malaria parasite.
AB  - Accurate regulation of microfilament dynamics is central to cell growth, motility
      and response to environmental stimuli. Stabilizing and depolymerizing proteins
      control the steady-state levels of filamentous (F-) actin. Capping protein (CP)
      binds to free barbed ends, thereby arresting microfilament growth and restraining
      elongation to remaining free barbed ends. In all CPs characterized to date, alpha
      and beta subunits form the active heterodimer. Here, we show in a eukaryotic
      parasitic cell that the two CP subunits can be functionally separated. Unlike the
      beta subunit, the CP alpha subunit of the apicomplexan parasite Plasmodium is
      refractory to targeted gene deletion during blood infection in the mammalian
      host. Combinatorial complementation of Plasmodium berghei CP genes with the
      orthologs from Plasmodium falciparum verified distinct activities of CP alpha and
      CP alpha/beta during parasite life cycle progression. Recombinant Plasmodium CP
      alpha could be produced in Escherichia coli in the absence of the beta subunit
      and the protein displayed F-actin capping activity. Thus, the functional
      separation of two CP subunits in a parasitic eukaryotic cell and the F-actin
      capping activity of CP alpha expand the repertoire of microfilament regulatory
      mechanisms assigned to CPs. 

PMID- 25565325
TI  - Widefield spectral monitoring of nanometer distance changes in DNA-templated
      plasmon rulers.
AB  - The nanometer-scale sensitivity of electromagnetic plasmon coupling allows the
      translation of minute morphological changes in nanostructures into macroscopic
      optical signals. We demonstrate here a widefield spectral analysis of 40 nm
      diameter gold nanoparticle (AuNP) dimers, linked by a short DNA double strand,
      using a low-cost color CCD camera and allowing a quantitative estimation of
      interparticle distances in a 3-20 nm range. This analysis can be extended to
      lower spacings and a parallel monitoring of dimer orientations by performing a
      simple polarization analysis. Our measurement approach is calibrated against
      confocal scattering spectroscopy using AuNP dimers that are distorted from a
      stretched geometry at low ionic strength to touching particles at high salt
      concentrations. We then apply it to identify dimers featuring two different
      conformations of the same DNA template and discuss the parallel colorimetric
      sensing of short sequence-specific DNA single strands using dynamic plasmon
      rulers. 

PMID- 25565327
TI  - Task-specific stability of multifinger steady-state action.
AB  - The authors explored task-specific stability during accurate multifinger force
      production tasks with different numbers of instructed fingers. Subjects performed
      steady-state isometric force production tasks and were instructed not to
      interfere voluntarily with transient lifting-and-lowering perturbations applied
      to the index finger. The main results were (a) intertrial variance in the space
      of finger modes at steady states was larger within the subspace that had no
      effect on the total force (the uncontrolled manifold [UCM]); (b) perturbations
      caused large deviations of finger modes within the UCM (motor equivalence); and
      (c) deviations caused by the perturbation showed larger variance within the UCM.
      No significant effects of the number of task fingers were noted in any of the 3
      indicators. The results are discussed within the frameworks of the UCM and
      referent configuration hypotheses. The authors conclude, in particular, that all
      the tasks were effectively 4-finger tasks with different involvement of task and
      nontask fingers. 

PMID- 25565326
TI  - Health-related quality of life in lung cancer survivors: Latent class and latent
      transition analysis.
AB  - BACKGROUND: Health-related quality of life (HRQOL) heterogeneity among cancer
      survivors may mask subgroups (classes) with different limitations and long-term
      outcomes. The authors determined the HRQOL classes that exist among lung cancer
      survivors, examined transitions among those classes over time, and compared
      survival outcomes of patients according to the classes present in the initial
      phase of care. METHODS: Lung cancer survivors in the Cancer Care Outcomes
      Research and Surveillance Consortium completed EuroQol 5-domain quality-of-life
      questionnaires 4.8 months (initial phase) and >1 year (survivorship phase) after
      diagnosis (n = 1396). Latent class analysis and latent transition analysis were
      used to determine HRQOL classes and transitions across time. Correlates of class
      membership were tested using multinomial logistic regression. Kaplan-Meier and
      Cox regression analyses were used to compare survival across class membership.
      RESULTS: Latent class analysis identified 4 classes at diagnosis and follow-up:
      1) poor HRQOL, 2) pain-dominant impairment, 3) mobility/usual activities
      impairment, and 4) good HRQOL. Probabilities of remaining in the same class were
      .87, .85, .82, and .73 for classes 4, 1, 3, and 2, respectively. Younger age,
      lower income, lower education, comorbidities, and a history of
      depression/emotional problems were associated with a greater likelihood of being
      in classes 1, 2, or 3 at follow-up. Patients in classes 1 and 3 had significantly
      lower median survival estimates than patients in class 4 (4.8 years, 3.8 years,
      and 5.5 years, respectively; P < .001). CONCLUSIONS: Examining the heterogeneity
      of HRQOL in lung cancer populations allows the identification of classes with
      different limitations and long-term outcomes and, thus, guides tailored and
      patient-centered provision of supportive care.

PMID- 25565329
TI  - The influence of the microscope lamp filament colour temperature on the process
      of digital images of histological slides acquisition standardization.
AB  - BACKGROUND: The aim of this study is to compare the digital images of the tissue
      biopsy captured with optical microscope using bright field technique under
      various light conditions. The range of colour's variation in
      immunohistochemically stained with 3,3'-Diaminobenzidine and Haematoxylin tissue
      samples is immense and coming from various sources. One of them is inadequate
      setting of camera's white balance to microscope's light colour temperature.
      Although this type of error can be easily handled during the stage of image
      acquisition, it can be eliminated with use of colour adjustment algorithms. The
      examination of the dependence of colour variation from microscope's light
      temperature and settings of the camera is done as an introductory research to the
      process of automatic colour standardization. METHODS: Six fields of view with
      empty space among the tissue samples have been selected for analysis. Each field
      of view has been acquired 225 times with various microscope light temperature and
      camera white balance settings. The fourteen randomly chosen images have been
      corrected and compared, with the reference image, by the following methods: Mean
      Square Error, Structural SIMilarity and visual assessment of viewer. RESULTS: For
      two types of backgrounds and two types of objects, the statistical image
      descriptors: range, median, mean and its standard deviation of chromaticity on a
      and b channels from CIELab colour space, and luminance L, and local colour
      variability for objects' specific area have been calculated. The results have
      been averaged for 6 images acquired in the same light conditions and camera
      settings for each sample. CONCLUSIONS: The analysis of the results leads to the
      following conclusions: (1) the images collected with white balance setting
      adjusted to light colour temperature clusters in certain area of chromatic space,
      (2) the process of white balance correction for images collected with white
      balance camera settings not matched to the light temperature moves image
      descriptors into proper chromatic space but simultaneously the value of luminance
      changes. So the process of the image unification in a sense of colour fidelity
      can be solved in separate introductory stage before the automatic image analysis.

PMID- 25565330
TI  - Influence of gravity upon some facial signs.
AB  - OBJECTIVES: Facial clinical signs and their integration are the basis of
      perception than others could have from ourselves, noticeably the age they imagine
      we are. Facial modifications in motion and their objective measurements before
      and after application of skin regimen are essential to go further in evaluation
      capacities to describe efficacy in facial dynamics. Quantification of facial
      modifications vis a vis gravity will allow us to answer about 'control' of facial
      shape in daily activities. METHODS: Standardized photographs of the faces of 30
      Caucasian female subjects of various ages (24-73 year) were successively taken at
      upright and supine positions within a short time interval. All these pictures
      were therefore reframed - any bias due to facial features was avoided when
      evaluating one single sign - for clinical quotation by trained experts of several
      facial signs regarding published standardized photographic scales. RESULTS: For
      all subjects, the supine position increased facial width but not height, giving a
      more fuller appearance to the face. More importantly, the supine position changed
      the severity of facial ageing features (e.g. wrinkles) compared to an upright
      position and whether these features were attenuated or exacerbated depended on
      their facial location. Supine station mostly modifies signs of the lower half of
      the face whereas those of the upper half appear unchanged or slightly
      accentuated. These changes appear much more marked in the older groups, where
      some deep labial folds almost vanish. These alterations decreased the perceived
      ages of the subjects by an average of 3.8 years. CONCLUSION: Although
      preliminary, this study suggests that a 90 degrees  rotation of the facial skin
      vis a vis gravity induces rapid rearrangements among which changes in tensional
      forces within and across the face, motility of interstitial free water among
      underlying skin tissue and/or alterations of facial Langer lines, likely play a
      significant role.

PMID- 25565328
TI  - Insights into the evolution of longevity from the bowhead whale genome.
AB  - The bowhead whale (Balaena mysticetus) is estimated to live over 200 years and is
      possibly the longest-living mammal. These animals should possess protective
      molecular adaptations relevant to age-related diseases, particularly cancer.
      Here, we report the sequencing and comparative analysis of the bowhead whale
      genome and two transcriptomes from different populations. Our analysis identifies
      genes under positive selection and bowhead-specific mutations in genes linked to
      cancer and aging. In addition, we identify gene gain and loss involving genes
      associated with DNA repair, cell-cycle regulation, cancer, and aging. Our results
      expand our understanding of the evolution of mammalian longevity and suggest
      possible players involved in adaptive genetic changes conferring cancer
      resistance. We also found potentially relevant changes in genes related to
      additional processes, including thermoregulation, sensory perception, dietary
      adaptations, and immune response. Our data are made available online
      (http://www.bowhead-whale.org) to facilitate research in this long-lived species.

PMID- 25565332
TI  - NeuO: a fluorescent chemical probe for live neuron labeling.
AB  - To address existing limitations in live neuron imaging, we have developed NeuO, a
      novel cell-permeable fluorescent probe with an unprecedented ability to label and
      image live neurons selectively over other cells in the brain. NeuO enables robust
      live neuron imaging and isolation in vivo and in vitro across species; its
      versatility and ease of use sets the basis for its development in a myriad of
      neuronal targeting applications. 

PMID- 25565331
TI  - S100 and annexin proteins identify cell membrane damage as the Achilles heel of
      metastatic cancer cells.
AB  - Mechanical activity of cells and the stress imposed on them by extracellular
      environment is a constant source of injury to the plasma membrane (PM). In
      invasive tumor cells, increased motility together with the harsh environment of
      the tumor stroma further increases the risk of PM injury. The impact of these
      stresses on tumor cell plasma membrane and mechanism by which tumor cells repair
      the PM damage are poorly understood. Ca(2+) entry through the injured PM
      initiates repair of the PM. Depending on the cell type, different organelles and
      proteins respond to this Ca(2+) entry and facilitate repair of the damaged plasma
      membrane. We recently identified that proteins expressed in various metastatic
      cancers including Ca(2+)-binding EF hand protein S100A11 and its binding partner
      annexin A2 are used by tumor cells for plasma membrane repair (PMR). Here we will
      discuss the involvement of S100, annexin proteins and their regulation of actin
      cytoskeleton, leading to PMR. Additionally, we will show that another S100 member
      -S100A4 accumulates at the injured PM. These findings reveal a new role for the
      S100 and annexin protein up regulation in metastatic cancers and identify these
      proteins and PMR as targets for treating metastatic cancers.

PMID- 25565333
TI  - [Outpatient Surgery in German ENT in Teaching Hospitals--Economic Nonsense?].
AB  - INTRODUCTION: There is an ever-increasing demand to increase efficiency and
      decrease costs in health care. This leads to an growing number of outpatient
      surgeries which are less cost effective. Especially in the setting of university
      teaching hospitals, this may lead to both an undersupply of qualified physicians,
      as well as to a worsening of clinical training of residents. In order to quantify
      a possible undersupply and estimate the expense of teaching residents, the time
      for medical procedures needs to be quantified and compared between board
      certified physicians and residents. This was the aim of the current study.
      MATERIAL AND METHODS: All outpatient adenotomies of children with or without
      paracentesis or tympanic drainage insertion performed in 2012 in 2 ENT teaching
      hospitals were analyzed. The length of the surgical procedure as well as the
      level of training of the surgeon was analyzed. Operating times of residents in
      training were analyzed stratified by training level and then compared to
      operation times of board-certified ENT surgeons. RESULTS: 255 procedures were
      analyzed. Significant differences of the mean operation time could be identified
      depending on the level of training of residents compared to board-certified ENT
      surgeons for all investigated training levels. E. g. 1(st) year residents'
      surgeries required 2.4 times more time than those of board-certified ENT
      surgeons. CONCLUSION: Based on an analysis of outpatient ENT-surgical procedures
      it becomes apparent that due to the extended operating times of residents in
      training outpatient surgery is by far less cost-effective than by board-certified
      physicians. To cope with the demand of teaching residents for their clinical
      training, more resources are necessary in the setting of teaching hospitals.

PMID- 25565334
TI  - [The Traumatic Tympanic Membrane Perforation - Aetiology and Therapy].
AB  - BACKGROUND: The use of cotton swabs is well known as a cause of a traumatic
      membrane perforation. More reasons are known. A detailed description of the
      aetiology and therapy in Germany does not exist. The treatment consist of a
      readaptation of the perforation an splinting of the tympanic membrane with paper
      sheets or silicon foils. MATERIALS AND METHODS: 238 patients with an acute
      tympanic membrane perforation were included in this retrospective study. They
      were treated between 2005 and 2010. RESULTS: The mean causes of a traumatic
      tympanic membrane perforation were slaps with the open hand (37.4%), the use of a
      cotton swab (19.3%) and high diving (13.0%). The perforations have been splinted
      with paper sheets or silicon foils. The rate of complete wound closure after
      splinting with different materials are comparable (71.9% and 81.8%). The side
      effects are low. CONCLUSION: This is the first study about the aetiology of
      traumatic tympanic membrane perforations in Germany. There is no statistic
      difference between the 2 materials for tympanic membrane splinting. A traumatic
      tympanic membrane perforation should be treatet at least to improve the air
      conduction threshold.

PMID- 25565336
TI  - Low dose CT image restoration using a database of image patches.
AB  - Reducing the radiation dose in CT imaging has become an active research topic and
      many solutions have been proposed to remove the significant noise and streak
      artifacts in the reconstructed images. Most of these methods operate within the
      domain of the image that is subject to restoration. This, however, poses
      limitations on the extent of filtering possible. We advocate to take into
      consideration the vast body of external knowledge that exists in the domain of
      already acquired medical CT images, since after all, this is what radiologists do
      when they examine these low quality images. We can incorporate this knowledge by
      creating a database of prior scans, either of the same patient or a diverse
      corpus of different patients, to assist in the restoration process. Our paper
      follows up on our previous work that used a database of images. Using images,
      however, is challenging since it requires tedious and error prone registration
      and alignment. Our new method eliminates these problems by storing a diverse set
      of small image patches in conjunction with a localized similarity matching
      scheme. We also empirically show that it is sufficient to store these patches
      without anatomical tags since their statistics are sufficiently strong to yield
      good similarity matches from the database and as a direct effect, produce image
      restorations of high quality. A final experiment demonstrates that our global
      database approach can recover image features that are difficult to preserve with
      conventional denoising approaches. 

PMID- 25565337
TI  - Teaching our learners patient-centered care goes beyond the exam room experience.

PMID- 25565335
TI  - The role of eating frequency on relative weight in urban school-age children.
AB  - BACKGROUND: The role of eating frequency on relative weight in childhood is not
      well understood. OBJECTIVE: To clarify this relationship by assessing the cross
      sectional and prospective relationships of weekday eating frequency with BMI z
      score (BMIz) and change in BMIz in a sample of schoolchildren. METHODS: Eating
      frequency, the average number of reported daily eating occasions, was assessed
      using two weekday 24-h diet recalls. BMIz was measured at baseline, 6 months and
      1 year in 155 urban schoolchildren, ages 9-15 years. Multiple linear regression
      models were used. RESULTS: Cross-sectional analyses at baseline suggest that BMIz
      was 0.23 units lower for each additional reported eating occasion (regression
      coefficient = -0.23; 95% confidence interval [CI]: -0.44, -0.07). From baseline
      to 6 months, BMIz increased by 0.03 units for each additional reported eating
      occasion (regression coefficient = 0.03; 95% CI: 0.01, 0.05). This relationship
      was no longer statistically significant at 1 year (regression coefficient = 0.01;
      95% CI: -0.01, 0.03). CONCLUSIONS: The findings suggest that the relationship of
      eating frequency with BMIz differs from that of change in BMIz. This difference
      may be due to methodological deficiencies of cross-sectional studies, challenges
      of dietary assessment or differences in eating patterns among normal and
      overweight youth. Controlled trials are needed to further clarify this
      relationship.

PMID- 25565338
TI  - Allergen expression in the European house dust mite Dermatophagoides
      pteronyssinus throughout development and response to environmental conditions.
AB  - House dust mites are a major source of allergy worldwide. While diagnosis and
      treatment based on mite extracts have remarkably advanced, little information
      exists on the expression of allergens in mites. We have studied gene expression
      of eight Dermatophagoides pteronyssinus (Trouessart) (Acari: Pyroglyphidae)
      allergens (Der p 1, 2, 3, 4, 5, 7, 10 and 21). All allergens showed higher
      transcription in nymphs compared with larvae or adults, with the only exception
      of Der p 10. The transcription of Der p 4 and Der p 10, together with the
      transcription and protein ratios Der p 1 to Der p 2, were higher in males than in
      females. One-week exposure of mite cultures to 16 or 35  degrees C (versus 24 
      degrees C) or low RH (44% versus 76%) significantly influenced the allergen gene
      transcription profile. Our results demonstrate that allergen expression is
      quantitatively and/or qualitatively influenced by mite development and sex, as
      well as by the environment. We suggest that monitoring allergen gene expression
      may be a useful tool to assist the optimization of mite cultures in the
      production of standardized allergenic extracts for clinical use. 

PMID- 25565340
TI  - Epitaxially grown strained pentacene thin film on graphene membrane.
AB  - Organic-graphene system has emerged as a new platform for various applications
      such as flexible organic photovoltaics and organic light emitting diodes. Due to
      its important implication in charge transport, the study and reliable control of
      molecular packing structures at the graphene-molecule interface are of great
      importance for successful incorporation of graphene in related organic devices.
      Here, an ideal membrane of suspended graphene as a molecular assembly template is
      utilized to investigate thin-film epitaxial behaviors. Using transmission
      electron microscopy, two distinct molecular packing structures of pentacene on
      graphene are found. One observed packing structure is similar to the well-known
      bulk-phase, which adapts a face-on molecular orientation on graphene substrate.
      On the other hand, a rare polymorph of pentacene crystal, which shows significant
      strain along the c-axis, is identified. In particular, the strained film exhibits
      a specific molecular orientation and a strong azimuthal correlation with
      underlying graphene. Through ab initio electronic structure calculations,
      including van der Waals interactions, the unusual polymorph is attributed to the
      strong graphene-pentacene interaction. The observed strained organic film growth
      on graphene demonstrates the possibility to tune molecular packing via graphene
      molecule interactions. 

PMID- 25565339
TI  - An extended Swedish national adoption study of alcohol use disorder.
AB  - IMPORTANCE: Alcohol use disorder (AUD) runs strongly in families. It is unclear
      to what extent the cross-generational transmission of AUD results from genetic vs
      environmental factors. OBJECTIVE: To determine to what extent genetic and
      environmental factors contribute to the risk for AUD. DESIGN, SETTING, AND
      PARTICIPANTS: Follow-up in 8 public data registers of adoptees, their biological
      and adoptive relatives, and offspring and parents from stepfamilies and not-lived
      with families in Sweden. In this cohort study, subtypes of AUD were assessed by
      latent class analysis. A total of 18,115 adoptees (born 1950-1993) and 171,989
      and 107,696 offspring of not-lived-with parents and stepparents, respectively
      (born 1960-1993). MAIN OUTCOMES AND MEASURES: Alcohol use disorder recorded in
      medical, legal, or pharmacy registry records. RESULTS: Alcohol use disorder in
      adoptees was significantly predicted by AUD in biological parents (odds ratio,
      1.46; 95% CI, 1.29-1.66) and siblings (odds ratio, 1.94; 95% CI, 1.55-2.44) as
      well as adoptive parents (odds ratio, 1.40; 95% CI, 1.09-1.80). Genetic and
      environmental risk indices created from biological and adoptive relatives acted
      additively on adoptee AUD liability. Results from biological and adoptive
      relatives were replicated and extended from examinations of, respectively, not
      lived-with parents and stepparents. Multivariate models in these families showed
      that AUD in offspring was significantly predicted by AUD, drug abuse, psychiatric
      illness, and crime in not-lived-with parents and by AUD, drug abuse, crime, and
      premature death in stepparents. Latent class analyses of adoptees and offspring
      of not-lived-with parents with AUDs revealed 3 AUD classes characterized by (1)
      female preponderance and high rates of psychiatric illness, (2) mild nonrecurrent
      symptoms, and (3) early-onset recurrence, drug abuse, and crime. These classes
      had distinct genetic signatures in the patterns of risk for various disorders in
      their not-lived-with parents and striking differences in the rates of recorded
      mood disorders. CONCLUSIONS AND RELEVANCE: Parent-offspring transmission of AUD
      results from both genetic and environmental factors. Genetic risk for AUD
      reflects both a specific liability to AUD and to other externalizing disorders.
      Environmental risk reflects features of both parental psychopathology and other
      aspects of the rearing environment. Alcohol use disorder is a heterogeneous
      syndrome and meaningful subtypes emerged from latent class analysis, which were
      validated by patterns of disorders in biological parents and specific psychiatric
      comorbidities. The general population contains informative family constellations
      that can complement more traditional adoption designs in clarifying the sources
      of parent-offspring resemblance.

PMID- 25565341
TI  - Base-pairing energies of protonated nucleobase pairs and proton affinities of 1
      methylated cytosines: model systems for the effects of the sugar moiety on the
      stability of DNA i-motif conformations.
AB  - Expansion of (CCG)n.(CGG)n trinucleotide repeats leads to hypermethylation of
      cytosine residues and results in Fragile X syndrome, the most common cause of
      inherited intellectual disability in humans. The (CCG)n.(CGG)n repeats adopt i
      motif conformations that are preferentially stabilized by base-pairing
      interactions of noncanonical protonated nucleobase pairs of cytosine (C(+).C).
      Previously, we investigated the effects of 5-methylation of cytosine on the base
      pairing energies (BPEs) using threshold collision-induced dissociation (TCID)
      techniques. In the present work, we extend our investigations to include
      protonated homo- and heteronucleobase pairs of cytosine, 1-methylcytosine, 5
      methylcytosine, and 1,5-dimethylcytosine. The 1-methyl substituent prevents most
      tautomerization processes of cytosine and serves as a mimic for the sugar moiety
      of DNA nucleotides. In contrast to permethylation of cytosine at the 5-position,
      1-methylation is found to exert very little influence on the BPE. All
      modifications to both nucleobases lead to a small increase in the BPEs, with 5
      methylation producing a larger enhancement than either 1-methyl or 1,5
      dimethylation. In contrast, modifications to a single nucleobase are found to
      produce a small decrease in the BPEs, again with 5-methylation producing a larger
      effect than 1-methylation. However, the BPEs of all of the protonated nucleobase
      pairs examined here significantly exceed those of canonical G.C and neutral C.C
      base pairs, and thus should still provide the driving force stabilizing DNA i
      motif conformations even in the presence of such modifications. The proton
      affinities of the methylated cytosines are also obtained from the TCID
      experiments by competitive analyses of the primary dissociation pathways that
      occur in parallel for the protonated heteronucleobase pairs. 

PMID- 25565342
TI  - Fluorescein sodium fluorescence microscope-integrated lymphangiography for
      lymphatic supermicrosurgery.
AB  - Microscope-integrated lymphangiography is a useful method in the field of
      lymphatic supermicrosurgery. Fluorescence based on indocyanine green (ICG) is the
      most commonly used. Fluorescein sodium is a fluorescent tracer used for retinal
      and neurosurgical angiography but not yet for lymphatic supermicrosurgery. In
      this report, we present a case in which the fluorescein sodium fluorescence
      microscope-integrated lymphangiography was used for assessment of lymphatic
      drainage pathway and patency in a patient treated for secondary lymphedema by
      lymphaticovenular anastomoses. Fluorescein sodium fluorescence microscope
      integrated lymphangiography was evaluated in a 67-year-old female presented for a
      Campisi clinical stage IV lymphedema of the upper limb. Transcutaneous guidance
      and vascular fluorescence were assessed. A comparison with ICG fluorescence was
      made intraoperatively. Two lymphaticovenular anastomoses were performed and their
      patency were checked by lymphangiography. Transcutaneous signal was found higher
      with fluorescein sodium fluorescence. Intraluminal visualization was possible
      with fluorescein sodium coloration during lymphaticovenular anastomoses. No
      adverse reaction occurred. The circumferential differential reduction rate of
      affected limb was 8.1% 3 months after lymphaticovenular anastomoses. The use of
      fluorescence microscope-integrated lymphangiography with fluorescein sodium may
      be superior to ICG fluorescence in assistance of lymphaticovenular anastomoses.

PMID- 25565343
TI  - Identifying the sources and processes of mercury in subtropical estuarine and
      ocean sediments using Hg isotopic composition.
AB  - The concentrations and isotopic compositions of mercury (Hg) in surface sediments
      of the Pearl River Estuary (PRE) and the South China Sea (SCS) were analyzed. The
      data revealed significant differences between the total Hg (THg) in fine-grained
      sediments collected from the PRE (8-251 MUg kg(-1)) and those collected from the
      SCS (12-83 MUg kg(-1)). Large spatial variations in Hg isotopic compositions were
      observed in the SCS (delta(202)Hg, from -2.82 to -2.100/00; Delta(199)Hg, from
      +0.21 to +0.450/00) and PRE (delta(202)Hg, from -2.80 to -0.680/00; Delta(199)Hg,
      from -0.15 to +0.160/00). The large positive Delta(199)Hg in the SCS indicated
      that a fraction of Hg has undergone Hg(2+) photoreduction processes prior to
      incorporation into the sediments. The relatively negative Delta(199)Hg values in
      the PRE indicated that photoreduction of Hg is not the primary route for the
      removal of Hg from the water column. The riverine input of fine particles played
      an important role in transporting Hg to the PRE sediments. In the deep ocean bed
      of the SCS, source-related signatures of Hg isotopes may have been altered by
      natural geochemical processes (e.g., Hg(2+) photoreduction and preferential
      adsorption processes). Using Hg isotope compositions, we estimate that river
      deliveries of Hg from industrial and urban sources and natural soils could be the
      main inputs of Hg to the PRE. However, the use of Hg isotopes as tracers in
      source attribution could be limited because of the isotope fractionation by
      natural processes in the SCS.

PMID- 25565345
TI  - Young women's access to and use of contraceptives: the role of providers'
      restrictions in urban Senegal.
AB  - CONTEXT: Contraceptive prevalence is very low in Senegal, particularly among
      young women. Greater knowledge is needed about the barriers young women face to
      using contraceptives, including barriers imposed by health providers. METHODS:
      Survey data collected in 2011 for the evaluation of the Urban Reproductive Health
      Initiative in Senegal were used to examine contraceptive use, method mix, unmet
      need and method sources among urban women aged 15-29 who were either currently
      married or unmarried but sexually active. Data from a sample of family planning
      providers were used to examine the prevalence of contraceptive eligibility
      restrictions based on age and marital status, and differences in such
      restrictions by method, facility type and provider characteristics. RESULTS:
      Modern contraceptive prevalence was 20% among young married women and 27% among
      young sexually active unmarried women; the levels of unmet need for contraception
      mostly for spacing-were 19% and 11%, respectively. Providers were most likely to
      set minimum age restrictions for the pill and the injectable-two of the methods
      most often used by young women in urban Senegal. The median minimum age for
      contraceptive provision was typically 18. Restrictions based on marital status
      were less common than those based on age. CONCLUSIONS: Training and education
      programs for health providers should aim to remove unnecessary barriers to
      contraceptive access.

PMID- 25565344
TI  - Fertility among orphans in rural Malawi: challenging common assumptions about
      risk and mechanisms.
AB  - CONTEXT: Although a substantial literature suggests that orphans suffer
      disadvantage relative to nonorphaned peers, the nature of this disadvantage and
      the mechanisms driving it are poorly understood. Some evidence suggests that
      orphans experience elevated fertility, perhaps because structural disadvantage
      leads them to engage in sexual risk-taking. An alternative explanation is that
      orphans intentionally become pregnant to achieve a sense of normality, acceptance
      and love. METHODS: Data from the 2006 wave of the Malawi Longitudinal Study of
      Families and Health on 1,033 young adults aged 15-25 were used to examine the
      relationship of maternal and paternal orphanhood with sexual risk indicators and
      desired and actual fertility. Regression analyses were used to adjust for
      covariates, including social and demographic characteristics and elapsed time
      since parental death. RESULTS: Twenty-six percent of respondents had lost their
      father and 15% their mother. Orphanhood was not associated with sexual risk
      taking. However, respondents whose mother had died in the past five years desired
      more children than did those whose mother was still alive (risk differences, 0.52
      among women and 0.97 among men). Actual fertility was elevated among women whose
      father had died more than five years earlier (0.31) and among men whose mother
      had died in the past five years (1.06) or more than five years earlier (0.47).
      CONCLUSION: The elevations in desired and actual fertility among orphans are
      consistent with the hypothesis that orphans intentionally become pregnant.
      Strategies that address personal desires for parenthood may need to be part of
      prevention programs aimed at orphaned youth.

PMID- 25565346
TI  - Risk for coerced sex among female youth in Ghana: roles of family context, school
      enrollment and relationship experience.
AB  - CONTEXT: A better understanding is needed of the variables that may influence the
      risk of experiencing coerced sex among adolescent females in Sub-Saharan Africa.
      METHODS: Data were collected from 700 female respondents who were interviewed in
      2010 and 2012 waves of a longitudinal study of behavioral risk for HIV infection
      among youth aged 13-14 or 18-19 and living in two towns in southeastern Ghana. A
      series of logistic regression models examined the influences of household
      composition and wealth, four family process variables (behavioral control,
      relationship quality, financial support, conflict), school enrollment and
      relationship experience on females' risk of experiencing coerced sex. RESULTS:
      Eighteen percent of respondents reported having experienced coerced sex prior to
      Wave 1, and 13% experienced it between Waves 1 and 2. In both cross-sectional and
      prospective models, the variable with the strongest association with having
      experienced coerced sex was having ever had a boyfriend (fully adjusted odds
      ratios, 4.5 and 2.6, respectively). In cross-sectional analyses, parental
      behavioral control was negatively associated with risk for coerced sex, while
      parental conflict was positively associated; these associations were not
      significant in the prospective analyses. Having a boyfriend appears to be the
      primary predictor of coerced sex among young females, beyond any influence of
      family, school or other household variables. CONCLUSIONS: More research is needed
      to understand the context of females' relationships with boyfriends in an effort
      to reduce the risk of sexual coercion and to promote the prevention of sexual
      violence perpetrated by males within these relationships.

PMID- 25565348
TI  - Achieving the goal of the London Summit on Family Planning by adhering to
      voluntary, rights-based family planning: what can we learn from past experiences
      with coercion?

PMID- 25565347
TI  - Gender-based power and couples' HIV risk in Uttar Pradesh and Uttarakhand, north
      India.
AB  - CONTEXT: Gender inequality is a long-recognized driver of the HIV epidemic.
      However, few studies have investigated the association between gender-based power
      and HIV risk in India, which has the world's third largest HIV epidemic. METHODS:
      Population-based data collected in 2003 from 3,385 couples residing in Uttar
      Pradesh and Uttarakhand, North India, were used to examine associations between
      gender-based power (wife's autonomy and husband's inequitable gender attitudes)
      and indicators of couples' HIV risk (whether the husband had had premarital sex
      with someone other than his eventual spouse, extramarital sex in the past year or
      STI symptoms in the past year). Structural equation modeling was used to create
      composite variables for the gender-based power measures and test their
      associations with HIV risk measures. RESULTS: Twenty-four percent of husbands had
      had premarital sex, 7% had had extramarital sex in the past year and 6% had had
      STI symptoms in the past year. Structural equation models indicated that wives
      who reported higher levels of autonomy were less likely than other wives to have
      husbands who had had extramarital sex in the past year (direct association) or
      STI symptoms in the past year (indirect association). Moreover, husbands who
      endorsed more inequitable gender attitudes were more likely than others to report
      having had premarital sex with someone other than their spouse, which in turn was
      associated with having had extramarital sex and STI symptoms in the past year.
      CONCLUSIONS: If the associations identified in this study reflect a causal
      relationship between gender-based power and HIV risk behavior, then HIV
      prevention programs that successfully address inequitable gender roles may reduce
      HIV risks in North India.

PMID- 25565349
TI  - The self: Your own worst enemy? A test of the self-invoking trigger hypothesis.
AB  - The self-invoking trigger hypothesis was proposed by Wulf and Lewthwaite [Wulf,
      G., & Lewthwaite, R. (2010). Effortless motor learning? An external focus of
      attention enhances movement effectiveness and efficiency. In B. Bruya (Ed.),
      Effortless attention: A new perspective in attention and action (pp. 75-101).
      Cambridge, MA: MIT Press] as a mechanism underlying the robust effect of
      attentional focus on motor learning and performance. One component of this
      hypothesis, relevant beyond the attentional focus effect, suggests that causing
      individuals to access their self-schema will negatively impact their learning and
      performance of a motor skill. The purpose of the present two studies was to
      provide an initial test of the performance and learning aspects of the self
      invoking trigger hypothesis by asking participants in one group to think about
      themselves between trial blocks-presumably activating their self-schema-to
      compare their performance and learning to that of a control group. In Experiment
      1, participants performed 2 blocks of 10 trials on a throwing task. In one
      condition, participants were asked between blocks to think about their past
      throwing experience. While a control group maintained their performance across
      blocks, the self group's performance was degraded on the second block. In
      Experiment 2, participants were asked to practice a wiffleball hitting task on
      two separate days. Participants returned on a third day to perform retention and
      transfer tests without the self-activating manipulation. Results indicated that
      the self group learned the hitting task less effectively than the control group.
      The findings reported here provide initial support for the self-invoking trigger
      hypothesis. 

PMID- 25565350
TI  - Functional and structural characterization of an unusual cofactor-independent
      oxygenase.
AB  - The vast majority of characterized oxygenases use bound cofactors to activate
      molecular oxygen to carry out oxidation chemistry. Here, we show that an enzyme
      of unknown activity, RhCC from Rhodococcus jostii RHA1, functions as an
      oxygenase, using 4-hydroxyphenylenolpyruvate as a substrate. This unique and
      complex reaction yields 3-hydroxy-3-(4-hydroxyphenyl)-pyruvate, 4
      hydroxybenzaldehyde, and oxalic acid as major products. Incubations with H2(18)O,
      (18)O2, and a substrate analogue suggest that this enzymatic oxygenation reaction
      likely involves a peroxide anion intermediate. Analysis of sequence similarity
      and the crystal structure of RhCC (solved at 1.78 A resolution) reveal that this
      enzyme belongs to the tautomerase superfamily. Members of this superfamily
      typically catalyze tautomerization, dehalogenation, or decarboxylation reactions
      rather than oxygenation reactions. The structure shows the absence of cofactors,
      establishing RhCC as a rare example of a redox-metal- and coenzyme-free
      oxygenase. This sets the stage to study the mechanistic details of cofactor
      independent oxygen activation in the unusual context of the tautomerase
      superfamily. 

PMID- 25565351
TI  - Assessment of phytotoxicity of anthracene in soybean (Glycine max) with a quick
      method of chlorophyll fluorescence.
AB  - A decrease in photosynthetic efficiency may indicate the toxic effects of
      environmental pollutants on higher plants. Measurement of chlorophyll (Chl) a
      fluorescence to assess the performance of photosystem II (PSII) was used as an
      bioindicator of toxicity of the polycyclic aromatic hydrocarbon (PAH) anthracene
      (ANT) in soybean plants. The results revealed that ANT treatment caused a
      reduction in quantum yield of PSII, damage to the oxygen evolving complex, as
      well as a significant reduction in performance index of PSII. However, change in
      performance index was more prominent, and it seems that the performance index is
      a more sensitive parameter to environmental contaminants. Moreover, a change in
      heterogeneity of PSII was also observed. The number of active reaction centres
      decreased with increasing concentration of ANT, as secondary plastoquinone
      reducing centres were converted into non-reducing centres, and PSIIalpha centres
      were converted into PSIIbeta and PSIIgamma centres. The influence of ANT on PSII
      heterogeneity could be an important reason for reductions in the PSII
      performance. 

PMID- 25565352
TI  - Sodium-glucose cotransporter 2 inhibitors and renal function-2.

PMID- 25565353
TI  - Genetic control of midbrain dopaminergic neuron development.
AB  - Midbrain dopaminergic neurons are involved in regulating motor control, reward
      behavior, and cognition. Degeneration or dysfunction of midbrain dopaminergic
      neurons is implicated in several neuropsychiatric disorders such as Parkinson's
      disease, substance use disorders, depression, and schizophrenia. Understanding
      the developmental processes that generate midbrain dopaminergic neurons will
      facilitate the generation of dopaminergic neurons from stem cells for cell
      replacement therapies to substitute degenerating cells in Parkinson's disease
      patients and will forward our understanding on how functional diversity of
      dopaminergic neurons in the adult brain is established. Midbrain dopaminergic
      neurons develop in a multistep process. Following the induction of the ventral
      midbrain, a distinct dopaminergic progenitor domain is specified and dopaminergic
      progenitors undergo proliferation, neurogenesis, and differentiation.
      Subsequently, midbrain dopaminergic neurons acquire a mature dopaminergic
      phenotype, migrate to their final position and establish projections and
      connections to their forebrain targets. This review will discuss insights gained
      on the signaling network of secreted molecules, cell surface receptors, and
      transcription factors that regulate specification and differentiation of midbrain
      dopaminergic progenitors and neurons, from the induction of the ventral midbrain
      to the migration of dopaminergic neurons. For further resources related to this
      article, please visit the WIREs website. CONFLICT OF INTEREST: The authors have
      declared no conflicts of interest for this article.

PMID- 25565356
TI  - Should we consider ezetimibe to reach even lower LDL-C targets?

PMID- 25565354
TI  - DNA methylation analysis of Homeobox genes implicates HOXB7 hypomethylation as
      risk factor for neural tube defects.
AB  - Neural tube defects (NTDs) are common birth defects of complex etiology. Though
      family- and population-based studies have confirmed a genetic component, the
      responsible genes for NTDs are still largely unknown. Based on the hypothesis
      that folic acid prevents NTDs by stimulating methylation reactions, epigenetic
      factors, such as DNA methylation, are predicted to be involved in NTDs. Homeobox
      (HOX) genes play a role in spinal cord development and are tightly regulated in a
      spatiotemporal and collinear manner, partly by epigenetic modifications. We have
      quantified DNA methylation for the different HOX genes by subtracting values from
      a genome-wide methylation analysis using leukocyte DNA from 10 myelomeningocele
      (MMC) patients and 6 healthy controls. From the 1575 CpGs profiled for the 4 HOX
      clusters, 26 CpGs were differentially methylated (P-value < 0.05; beta-difference
      > 0.05) between MMC patients and controls. Seventy-seven percent of these CpGs
      were located in the HOXA and HOXB clusters, with the most profound difference for
      3 CpGs within the HOXB7 gene body. A validation case-control study including 83
      MMC patients and 30 unrelated healthy controls confirmed a significant
      association between MMC and HOXB7 hypomethylation (-14.4%; 95% CI: 11.9-16.9%; P
      value < 0.0001) independent of the MTHFR 667C>T genotype. Significant HOXB7
      hypomethylation was also present in 12 unaffected siblings, each related to a MMC
      patient, suggestive of an epigenetic change induced by the mother. The inclusion
      of a neural tube formation model using zebrafish showed that Hoxb7a
      overexpression but not depletion resulted in deformed body axes with dysmorphic
      neural tube formation. Our results implicate HOXB7 hypomethylation as risk factor
      for NTDs and highlight the importance for future genome-wide DNA methylation
      analyses without preselecting candidate pathways. 

PMID- 25565357
TI  - Amperometric detection of single vesicle acetylcholine release events from an
      artificial cell.
AB  - Acetylcholine is a highly abundant nonelectroactive neurotransmitter in the
      mammalian central nervous system. Neurochemical release occurs on the millisecond
      time scale, requiring a fast, sensitive sensor such as an enzymatic amperometric
      electrode. Typically, the enzyme used for enzymatic electrochemical sensors is
      applied in excess to maximize signal. Here, in addition to sensitivity, we have
      also sought to maximize temporal resolution, by designing a sensor that is
      sensitive enough to work at near monolayer enzyme coverage. Reducing the enzyme
      layer thickness increases sensor temporal resolution by decreasing the distance
      and reducing the diffusion time for the enzyme product to travel to the sensor
      surface for detection. In this instance, the sensor consists of electrodeposited
      gold nanoparticle modified carbon fiber microelectrodes (CFMEs). Enzymes often
      are sensitive to curvature upon surface adsorption; thus, it was important to
      deposit discrete nanoparticles to maintain enzyme activity while depositing as
      much gold as possible to maximize enzyme coverage. To further enhance
      sensitivity, the enzymes acetylcholinesterase (AChE) and choline oxidase (ChO)
      were immobilized onto the gold nanoparticles at the previously determined optimal
      ratio (1:10 AChE/ChO) for most efficient sequential enzymatic activity. This
      optimization approach has enabled the rapid detection to temporally resolve
      single vesicle acetylcholine release from an artificial cell. The sensor
      described is a significant advancement in that it allows for the recording of
      acetylcholine release on the order of the time scale for neurochemical release in
      secretory cells.

PMID- 25565360
TI  - Differentiating 'clinical' and 'non-clinical' depression.
AB  - OBJECTIVE: There has been increasing concern about extensions to the definition
      of 'clinical' depression, but little evident investigation as to how clinical and
      non-clinical depressive states might best be differentiated. This review
      considers the potential of many candidate symptom and non-symptom parameters.
      METHOD: We overview representative concerns and theories about the nature of
      psychiatric disorders before reviewing the potential utility of candidate
      parameters for differentiating clinical and non-clinical depressive states.
      RESULTS: While we detail limitations to all candidate parameters designed to
      distinguish between clinical and non-clinical depression, their actual utility
      may only be able to be judged by empirical testing across appropriate comparison
      groups. CONCLUSION: We argue for initial comparisons being made between
      prototypically defined categorical (i.e. psychotic, melancholic and bipolar)
      depressive disease states and residual non-melancholic clinical depressive
      states, before considering how each of those two clinical subsets might differ
      from non-clinical depressive mood states.

PMID- 25565361
TI  - Optical properties of disilane-bridged donor-acceptor architectures: strong
      effect of substituents on fluorescence and nonlinear optical properties.
AB  - A series of disilane-bridged donor-acceptor architectures 1-9 containing strong
      electron-donating and -withdrawing substituents were designed and synthesized in
      acceptable yields. The substituents substantially affected the fluorescence and
      nonlinear optical properties of the compounds. In the solid state, the compounds
      showed purple-blue fluorescence (lambda(em) = 360-420 nm) with high quantum
      yields (up to 0.81). Compound 3, which had p-N,N-dimethylamino and o-cyano
      substituents, exhibited optical second harmonic generation (activity 2.9 times
      that of urea, calculated molecular hyperpolarizability beta = 1.6 * 10(-30) esu)
      in the powder state. Density functional theory calculations for the ground and
      excited states indicated that both the locally excited state and the
      intramolecular charge transfer excited state make important contributions to the
      luminescence behavior.

PMID- 25565359
TI  - Pharmacological treatment of atherosclerosis: an unresolved issue.

PMID- 25565362
TI  - Postharvest biology and technology of pomegranate.
AB  - Pomegranate is a subtropical and tropical fruit of great importance from a health
      point of view. Despite increasing consumer awareness of the health benefits of
      pomegranate, consumption of the fruit is still limited owing to poor postharvest
      handling, storage recommendations, short shelf life and quality deterioration
      during transportation, storage and marketing. The occurrence of physiological
      disorders such as husk scald, splitting and chilling injury is another challenge
      reducing marketability and consumer acceptance. Recently, notable work on
      postharvest biology and technology has been done. Pomegranate is highly sensitive
      to low-oxygen (<5 kPa) atmospheres, chilling injury and decay. One of the major
      problems associated with pomegranate fruit is excessive weight loss, which may
      result in hardening of the husk and browning of the rind and arils. To reduce
      chilling injury incidence and to extend storability and marketing of
      pomegranates, good results were obtained with polyamine, heat, salicylic acid,
      methyl jasmonate or methyl salicylate treatments prior to cold storage. This
      article reviews the maturity indices, changes during maturation and ripening,
      postharvest physiology and technology of pomegranate fruit as well as the various
      postharvest treatments for maintaining fruit quality.

PMID- 25565363
TI  - Impact of comorbidities on physical activity in COPD.
AB  - BACKGROUND AND OBJECTIVE: Both comorbidities and physical inactivity have been
      shown to impair quality of life and contribute to hospital admissions and
      mortality in chronic obstructive pulmonary disease (COPD) patients. We
      hypothesized that the comorbid status predicts the level of daily physical
      activity (PA) in COPD. METHODS: In 228 patients with COPD (76% men; median
      (quartiles) age: 64 (59/69) years; percentage of predicted forced expiratory
      volume in 1 s (FEV1 % pred): 44 (31/63)), comorbidities were assessed by medical
      history, clinical interviews, examination and blood analysis. PA level (PAL) was
      measured by an activity monitor (SenseWear Pro, Bodymedia Inc., Pittsburgh, PA,
      USA). The association between PAL and comorbidities was investigated by
      univariate and multivariate regression analysis. RESULTS: Seventy-nine percent of
      the COPD patients had at least one additional chronic comorbidity, 56% had two or
      more comorbidities and 35% had three or more comorbidities. In univariate
      analysis body mass index, the number of pack years and having at least one
      additional comorbidity was negatively associated with PAL while there was a
      positive nonlinear association between FEV1 and PAL. The presence of at least one
      additional comorbidity was independently associated with PAL irrespective of
      airflow limitation. CONCLUSIONS: In this cohort, almost 80% of COPD patients had
      at least one additional chronic comorbidity. The level of daily PA seems to be
      significantly impaired by the presence of comorbidities irrespective of the type
      of comorbidity and independent of the degree of airflow limitation. CLINICAL
      TRIAL REGISTRATION: NCT01527773 at http://www.clinicalTrials.gov.

PMID- 25565365
TI  - A small-molecule protein-protein interaction inhibitor of PARP1 that targets its
      BRCT domain.
AB  - Poly(ADP-ribose)polymerase-1 (PARP1) is a BRCT-containing enzyme (BRCT = BRCA1 C
      terminus) mainly involved in DNA repair and damage response and a validated
      target for cancer treatment. Small-molecule inhibitors that target the PARP1
      catalytic domain have been actively pursued as anticancer drugs, but are
      potentially problematic owing to a lack of selectivity. Compounds that are
      capable of disrupting protein-protein interactions of PARP1 provide an
      alternative by inhibiting its activities with improved selectivity profiles.
      Herein, by establishing a high-throughput microplate-based assay suitable for
      screening potential PPI inhibitors of the PARP1 BRCT domain, we have discovered
      that (+/-)-gossypol, a natural product with a number of known biological
      activities, possesses novel PARP1 inhibitory activity both in vitro and in cancer
      cells and presumably acts through disruption of protein-protein interactions. As
      the first known cell-permeable small-molecule PPI inhibitor of PAPR1, we further
      established that (-)-gossypol was likely the causative agent of PARP1 inhibition
      by promoting the formation of a 1:2 compound/PARP1 complex by reversible
      formation of a covalent imine linkage.

PMID- 25565358
TI  - Preclinical evidence implicating corticotropin-releasing factor signaling in
      ethanol consumption and neuroadaptation.
AB  - The results of many studies support the influence of the corticotropin-releasing
      factor (CRF) system on ethanol (EtOH) consumption and EtOH-induced
      neuroadaptations that are critical in the addiction process. This review
      summarizes the preclinical data in this area after first providing an overview of
      the components of the CRF system. This complex system involves hypothalamic and
      extra-hypothalamic mechanisms that play a role in the central and peripheral
      consequences of stressors, including EtOH and other drugs of abuse. In addition,
      several endogenous ligands and targets make up this system and show differences
      in their involvement in EtOH drinking and in the effects of chronic or repeated
      EtOH treatment. In general, genetic and pharmacological approaches paint a
      consistent picture of the importance of CRF signaling via type 1 CRF receptors
      (CRF(1)) in EtOH-induced neuroadaptations that result in higher levels of intake,
      encourage alcohol seeking during abstinence and alter EtOH sensitivity.
      Furthermore, genetic findings in rodents, non-human primates and humans have
      provided some evidence of associations of genetic polymorphisms in CRF-related
      genes with EtOH drinking, although additional data are needed. These results
      suggest that CRF(1) antagonists have potential as pharmacotherapeutics for
      alcohol use disorders. However, given the broad and important role of these
      receptors in adaptation to environmental and other challenges, full antagonist
      effects may be too profound and consideration should be given to treatments with
      modulatory effects.

PMID- 25565364
TI  - Efficacy and safety of a fixed-dose combination of dutasteride and tamsulosin
      treatment (Duodart((r)) ) compared with watchful waiting with initiation of
      tamsulosin therapy if symptoms do not improve, both provided with lifestyle
      advice, in the management of treatment-naive men with moderately symptomatic
      benign prostatic hyperplasia: 2-year CONDUCT study results.
AB  - OBJECTIVE: To investigate whether a fixed-dose combination (FDC) of 0.5 mg
      dutasteride and 0.4 mg tamsulosin is more effective than watchful waiting with
      protocol-defined initiation of tamsulosin therapy if symptoms did not improve (WW
      All) in treatment-naive men with moderately symptomatic benign prostatic
      hyperplasia (BPH) at risk of progression. PATIENTS AND METHODS: This was a
      multicentre, randomised, open-label, parallel-group study (NCT01294592) in 742
      men with an International Prostate Symptom Score (IPSS) of 8-19, prostate volume
      >=30 mL and total serum PSA level of >=1.5 ng/mL. Patients were randomised to FDC
      (369 patients) or WW-All (373) and followed for 24 months. All patients were
      given lifestyle advice. The primary endpoint was symptomatic improvement from
      baseline to 24 months, measured by the IPSS. Secondary outcomes included BPH
      clinical progression, impact on quality of life (QoL), and safety. RESULTS: The
      change in IPSS at 24 months was significantly greater for FDC than WW-All (-5.4
      vs -3.6 points, P < 0.001). With FDC, the risk of BPH progression was reduced by
      43.1% (P < 0.001); 29% and 18% of men in the WW-All and FDC groups had clinical
      progression, respectively, comprising symptomatic progression in most patients.
      Improvements in QoL (BPH Impact Index and question 8 of the IPSS) were seen in
      both groups but were significantly greater with FDC (P < 0.001). The safety
      profile of FDC was consistent with established profiles of dutasteride and
      tamsulosin. CONCLUSION: FDC therapy with dutasteride and tamsulosin, plus
      lifestyle advice, resulted in rapid and sustained improvements in men with
      moderate BPH symptoms at risk of progression with significantly greater symptom
      and QoL improvements and a significantly reduced risk of BPH progression compared
      with WW plus initiation of tamsulosin as per protocol.

PMID- 25565366
TI  - Application of endocrine disruptor screening program fish short-term reproduction
      assay: Reproduction and endocrine function in fathead minnow (Pimephales
      promelas) and killifish (Fundulus heteroclitus) exposed to Bermuda pond sediment.
AB  - A modified tier 1 Endocrine Disruptor Screening Program (EDSP) 21-d fish short
      term reproduction assay (FSTRA) was used to evaluate the effects of sediment
      exposure from freshwater and brackish ponds in Bermuda on reproductive fecundity
      and endocrine function in fathead minnow (Pimephales promelas) and killifish
      (Fundulus heteroclitus). Reproductively active male and female fish were exposed
      to control sediment and sediment from 2 freshwater ponds (fathead minnow) and 2
      marine ponds (killifish) contaminated with polyaromatic hydrocarbons and metals
      via flow-through exposure for 21 d. Reproductive fecundity was monitored daily.
      At termination, the status of the reproductive endocrine system was assessed by
      the gonadosomatic index, gonadal histology, plasma steroids (estrogen [E2],
      testosterone [T], and 11-ketotestosterone [11-KT]), steroidogenic enzymes
      (aromatase and combined 3beta/17beta -hydroxysteroid dehydrogenase [3beta/17beta
      HSD]), and plasma vitellogenin (VTG). Decreased reproductive fecundity, lower
      male body weight, and altered endocrinological measures of reproductive status
      were observed in both species. Higher plasma T levels in female minnows and 11-KT
      levels in both male and female minnows and female killifish exposed to freshwater
      and brackish sediments, respectively. Decreased female E2 and VTG levels and
      gonadal cytochrome P19 (aromatase) activity were also found in sediment exposed
      females from both species. No effect on female 3beta/17beta-HSD activity was
      found in either species. The FSTRA provided a robust model capable of
      modification to evaluate reproductive effects of sediment exposure in fish.

PMID- 25565367
TI  - Myopia and glaucoma: sorting out the difference.
AB  - PURPOSE OF REVIEW: The aim of the present review was to summarize the evidence
      implicating the association between myopia and glaucoma, the possible underlying
      mechanisms for this relation, and the controversies surrounding detection of
      glaucomatous changes in coexisting myopia. RECENT FINDINGS: Numerous studies have
      shown that increasing categories of myopia are associated with a higher risk for
      optic neuropathy and glaucoma-like visual field defects. Recently, some high
      resolution imaging modalities have been developed that aid further detection of
      the microanatomical changes of the optic nerve head and thus may provide a new
      insight to explain the association between myopia and glaucoma. Although the
      highly myopic eye usually shows many structural and functional defects that are
      difficult to distinguish from those caused by glaucoma, some new methods have
      been introduced to better differentiate between these changes. SUMMARY: The
      interaction of myopia with glaucoma risk remains complex, largely because of the
      retinal and nerve fiber layer damage that occurs in myopia alone. Whether to
      treat for glaucoma relies on the suspicion level of the clinician who must
      consider other risk factors for vision loss. Ultimately, it is the progression of
      glaucoma-like findings that determines whether a myopic patient has glaucoma.

PMID- 25565369
TI  - Resistant hypertension and renal denervation where to now?
AB  - Treatment resistant hypertension (TRH) is a major clinical problem with limited
      treatment options. Renal denervation (RDN) arose as a safe and very effective
      treatment for TRH with early studies showing dramatic blood pressure reductions
      however subsequent studies have not shown such a benefit. This review discusses
      the pathophysiology of TRH and the results of the published studies in RDN for
      TRH. The initial symplicity (1 and 2) studies using the Ardian RDN catheter
      showed that office blood pressures were significantly reduced 6 months following
      the procedure. However these initial studies were limited by a lack of a true
      control group and inadequate blinding. Subsequent studies (symplicity 3 and
      simplicity flex) included patients with elevated blood pressures on 24 hr
      ambulatory blood pressure monitor as well as office measurements. Furthermore,
      both included a sham arm where patients were randomized to undergo renal
      angiography alone or RDN, patients were blinded to whether they were in the
      treatment or sham arm. These more recent studies showed that in both the control
      and treatment group while there was a significant BP reduction from baseline
      there was no difference between the groups. Thus RDN appears to have no benefit
      in blood pressure reduction in those with TRH. RDN currently should only be used
      in patients with TRH as part of a properly designed clinical study. Pre clinical
      data suggests that renal sympathetic overactivity is an issue in younger
      hypertensive patients and this may be the group in which future studies using RDN
      should focus. 

PMID- 25565368
TI  - The role of lens extraction in the current management of primary angle-closure
      glaucoma.
AB  - PURPOSE OF REVIEW: Lens extraction for primary angle-closure glaucoma (PACG) is a
      subject of increased interest recently, with advocates promoting its benefits of
      anatomical opening of the angle, intraocular pressure (IOP) reduction and
      improved vision. The present review seeks to evaluate recent available evidence
      to provide clarity on this potential intervention within the armamentarium of
      approaches for PACG. RECENT FINDINGS: The emergence of recent case-control
      studies, cohort studies and randomized controlled trials has provided a stronger
      evidence base to equip ophthalmic surgeons with the necessary information to
      utilize lens extraction in the management of PACG, and to consider whether this
      should be combined with trabeculectomy or goniosynechialysis. Imaging modalities
      such as anterior segment optical coherence tomography have yielded new insights
      into the mechanical features of the lens in angle closure, with the lens
      thickness and lens vault now quantifiable. A trend is emerging regarding the
      improvement in IOP control, reduced complication rates and reduced need for IOP
      lowering medications in patients who undergo lens extraction for PACG. These
      issues are discussed, along with aspects of preoperative assessment and surgical
      techniques. SUMMARY: Good outcomes in terms of long-term IOP control have been
      found following lens extraction for PACG. Lens extraction should be considered in
      patients with PACG, especially with hyperopia, or a thick and anteriorly vaulted
      lens.

PMID- 25565370
TI  - Transforming plastic surfaces with electrophilic backbones from hydrophobic to
      hydrophilic.
AB  - We demonstrate a simple nonaqueous reaction scheme for transforming the surface
      of plastics from hydrophobic to hydrophilic. The chemical modification is
      achieved by base-catalyzed trans-esterification with polyols. It is permanent,
      does not release contaminants, and causes no optical or mechanical distortion of
      the plastic. We present contact angle measurements to show successful
      modification of several types of plastics including poly(ethylene terephthalate)
      (PET) and polycarbonate (PC). Its applicability to blood analysis is explored
      using chemically modified PET blood collection tubes and found to be quite
      satisfactory. We expect this approach will reduce the cost of manufacturing
      plastic devices with optimized wettability and can be generalized to other types
      of plastic materials having an electrophilic linkage as its backbone. 

PMID- 25565371
TI  - Interprofessional education through service-learning: lessons from a student-led
      free clinic.
AB  - The academic community must replicate and strengthen existing models for
      interprofessional education (IPE) to meet widespread calls for team-based patient
      centered care. One effective but under-explored possibility for IPE is through
      student-led clinics, which now exist in the majority of medical schools. This
      short report presents the Indiana University Student Outreach Clinic (IU-SOC),
      which involves seven different professional programs across three institutions,
      as a model for how IPE can be delivered formally through service learning.
      Lessons learned, such as nurturing an intentional interprofessional program,
      structured orientation and reflection, and resource and knowledge sharing between
      the clinic and academic institutions, can be applied to all student-led clinics,
      but also can inform other IPE initiatives in health professional curricula. 

PMID- 25565373
TI  - Pharmacoinformatics analysis to identify inhibitors of Mtb-ASADH.
AB  - Aspartate-semialdehyde dehydrogenase (ASADH; EC 1.2.1.11) is a key enzyme in the
      biosynthesis of essential amino acids in prokaryotes and fungi, inhibition of
      ASADH leads to the development of novel antitubercular agents. In the present
      work, a combined structure and ligand-based pharmacophore modeling, molecular
      docking, and molecular dynamics (MD) approaches were employed to identify potent
      inhibitors of mycobacterium tuberculosis (Mtb)-ASADH. The structure-based
      pharmacophore hypothesis consists of three hydrogen bond acceptor (HBA), two
      negatively ionizable, and one positively ionizable center, while ligand-based
      pharmacophore consists of additional one HBA and one hydrogen bond donor
      features. The validated pharmacophore models were used to screen the chemical
      databases (ZINC and NCI). The screened hits were subjected to ADME and toxicity
      filters, and subsequently to the molecular docking analysis. Best-docked 25
      compounds carry the characteristics of highly electronegative functional groups (
      COOH and -NO2) on both sides and exhibited the H-bonding interactions with highly
      conserved residues Arg99, Arg249, and His256. For further validation of docking
      results, MD simulation studies were carried out on two representative compounds
      NSC51108 and ZINC04203124. Both the compounds remain bound to the key active
      residues of Mtb-ASADH during the MD simulations. These identified hits can be
      further used for lead optimization and in the design more potent inhibitors
      against Mtb-ASADH. 

PMID- 25565372
TI  - Aptamer-conjugated graphene oxide membranes for highly efficient capture and
      accurate identification of multiple types of circulating tumor cells.
AB  - Tumor metastasis is responsible for 1 in 4 deaths in the United States. Though it
      has been well-documented over past two decades that circulating tumor cells
      (CTCs) in blood can be used as a biomarker for metastatic cancer, there are
      enormous challenges in capturing and identifying CTCs with sufficient sensitivity
      and specificity. Because of the heterogeneous expression of CTC markers, it is
      now well understood that a single CTC marker is insufficient to capture all CTCs
      from the blood. Driven by the clear need, this study reports for the first time
      highly efficient capture and accurate identification of multiple types of CTCs
      from infected blood using aptamer-modified porous graphene oxide membranes. The
      results demonstrate that dye-modified S6, A9, and YJ-1 aptamers attached to 20-40
      MUm porous garphene oxide membranes are capable of capturing multiple types of
      tumor cells (SKBR3 breast cancer cells, LNCaP prostate cancer cells, and SW-948
      colon cancer cells) selectively and simultaneously from infected blood. Our
      result shows that the capture efficiency of graphene oxide membranes is ~95% for
      multiple types of tumor cells; for each tumor concentration, 10 cells are present
      per milliliter of blood sample. The selectivity of our assay for capturing
      targeted tumor cells has been demonstrated using membranes without an antibody.
      Blood infected with different cells also has been used to demonstrate the
      targeted tumor cell capturing ability of aptamer-conjugated membranes. Our data
      also demonstrate that accurate analysis of multiple types of captured CTCs can be
      performed using multicolor fluorescence imaging. Aptamer-conjugated membranes
      reported here have good potential for the early diagnosis of diseases that are
      currently being detected by means of cell capture technologies.

PMID- 25565374
TI  - CD36 gene variants in early prediction of type 2 diabetes mellitus.
AB  - Type 2 diabetes (T2DM) is a noncommunicable disease affecting huge populations in
      India and abroad. Single-nucleotide polymorphisms (SNPs) in CD36, a macrophage
      scavenger receptor, have been implicated in the pathogenesis of T2DM and its
      complications. Eleven SNPs in the CD36 gene and their association with 100 each
      of control subjects and T2DM patients were investigated in the present study. The
      haplotype analysis of a few significant SNPs was carried out in individuals from
      families with diabetic history to evaluate its utility in disease prediction.
      Polymerase chain reaction-restriction fragment length polymorphism was used for
      genotyping. Ten families with a family history of diabetes were identified and
      blood samples were collected from as many family members as possible. Genotyping
      of three SNPs, namely rs1761667 (G>A) in exon 1 A, rs3211938 (T>G) in exon 10,
      and rs3212018 (16 bp del) in exon 14, was performed in all samples. Our results
      suggested that individuals having a GATTC1 haplotype might be at risk of
      developing T2DM (p<0.001) and, therefore, might be susceptible to related
      complications. Moreover, the presence of A, G, and G alleles of SNPs rs1761667
      (G>A), rs3211938 (T>G), and rs1984112 (T>G) tends to have increased BMI,
      respectively. Such studies may be helpful for disease prediction in individuals
      at risk of T2DM. The predictive potential of CD36 variants can be explored with
      more families in the study population to use this as a genetic marker. 

PMID- 25565376
TI  - Platelet-derived microparticles induce polymorphonuclear leukocyte-mediated
      damage of human pulmonary microvascular endothelial cells.
AB  - BACKGROUND: Platelets (PLTs) stored at 22 degrees C accumulate microparticles and
      biologic response modifiers (BRMs) that induce inflammatory reactions in
      transfusion recipients. However, soluble BRMs are fully diluted in the
      recipient's blood circulation. The mechanisms by which BRMs exert their effects
      have not been elucidated. The objectives of this study were to determine the
      effect of PLT microparticles (PMPs) on polymorphonuclear leukocyte (PMN)-mediated
      human pulmonary microvascular endothelial cell (HMVEC) damage and determine the
      role of soluble CD40 ligand (sCD40L). STUDY DESIGN AND METHODS: PMPs were
      isolated from apheresis PLT concentrates. We used a two-insult in vitro model of
      HMVEC damage to investigate the effects of PMP and sCD40L and role of apocynin,
      an inhibitor of PMN respiratory burst. Their priming activities were measured
      using hydrogen peroxide production. The expression of intercellular cell adhesion
      molecule-1 (ICAM-1) and integrin alphaM (CD11b) were also determined. RESULTS:
      Lipopolysaccharide (LPS)-activated HMVEC damage and PMN respiratory burst depend
      on the presence of PMP and the concentration of sCD40L. PMP-induced PMN-mediated
      HMVEC damage was significantly reduced by apocynin-treated PMNs (p < 0.05). The
      surface expression of ICAM-1 on HMVEC was increased by LPS stimulation. The
      expression of CD11b on PMNs was increased by PMP priming. Blocking ICAM-1 with a
      monoclonal antibody (MoAb) CD54 significantly reduced HMVEC damage (p < 0.05).
      The treatment of endothelial cells but not PMN with a MoAb targeting CD40 failed
      to prevent the HMVEC damage caused by PMPs (p > 0.05). CONCLUSION: PMPs carry a
      concentrated CD40L signal, promote PMN-mediated HMVEC damage, and may affect the
      development of transfusion-related acute lung injury.

PMID- 25565375
TI  - Proinflammatory TLR signalling is regulated by a TRAF2-dependent proteolysis
      mechanism in macrophages.
AB  - Signal transduction from toll-like receptors (TLRs) is important for innate
      immunity against infections, but deregulated TLR signalling contributes to
      inflammatory disorders. Here we show that myeloid cell-specific ablation of TRAF2
      greatly promotes TLR-stimulated proinflammatory cytokine expression in
      macrophages and exacerbates colitis in an animal model of inflammatory bowel
      disease. TRAF2 deficiency does not enhance upstream signalling events, but it
      causes accumulation of two transcription factors, c-Rel and IRF5, known to
      mediate proinflammatory cytokine induction. Interestingly, TRAF2 controls the
      fate of c-Rel and IRF5 via a proteasome-dependent mechanism that also requires
      TRAF3 and the E3 ubiquitin ligase cIAP. We further show that TRAF2 also regulates
      inflammatory cytokine production in tumour-associated macrophages and facilitates
      tumour growth. These findings demonstrate an unexpected anti-inflammatory
      function of TRAF2 and suggest a proteasome-dependent mechanism that limits the
      proinflammatory TLR signalling. 

PMID- 25565378
TI  - Etomica: an object-oriented framework for molecular simulation.
AB  - We describe the design of an object-oriented library of software components that
      are suitable for constructing simulations of systems of interacting particles.
      The emphasis of the discussion is on the general design of the components and how
      they interact, and less on details of the programming interface or its
      implementation. Example code is provided as an aid to understanding object
      oriented programming structures and to demonstrate how the framework is applied.

PMID- 25565379
TI  - Complex equilibria, speciation, and heteroprotein coacervation of lactoferrin and
      beta-lactoglobulin.
AB  - There has been a resurgence of interest in complex coacervation, a form of liquid
      liquid phase separation (LLPS) in systems of oppositely charged macroions, but
      very few reports describe the somewhat anomalous coacervation between acidic and
      basic proteins, which occurs under very narrow ranges of conditions. We sought to
      identify the roles of equilibrium interprotein complexes during the coacervation
      of beta-lactoglobulin dimer (BLG2) with lactoferrin (LF) and found that this LLPS
      arises specifically from LF(BLG2)2. We followed the progress of complexation and
      coacervation as a function of r, the LF/BLG molar ratio, using turbidity to
      monitor the degree of coacervation and proton release and dynamic light
      scattering (DLS) to assess the stoichiometry and abundance of complexes.
      Isothermal titration calorimetry (ITC) showed that initial complex formation is
      endothermic, but a large exotherm related to coacervate formation obscured other
      regions. On the basis of turbidimetry, proton release, and DLS, we propose a
      speciation diagram that presents the abundance of various complexes as a function
      of r. Although multiple species could be simultaneously present, distinct regions
      could be identified corresponding to equilibria among particular protein pairs. 

PMID- 25565380
TI  - Dexmedetomidine preconditioning attenuates global cerebral ischemic injury
      following asphyxial cardiac arrest.
AB  - BACKGROUND/AIMS: To investigate the protection effect of dexmedetomidine
      preconditioning on global cerebral ischemic injury following asphyxial cardiac
      arrest (CA) in rats. METHODS: Seventy-two rats were randomly assigned into three
      groups, sham group (no asphyxia), control group (asphyxia only), and
      dexmedetomidine preconditioned group (asphyxia + dexmedetomidine).
      Dexmedetomidine was administered 5 minutes before an 8 min of asphyxia. Rats were
      resuscitated by a standardized method. Blood O(2) and CO(2) partial pressures
      were, pH, base excess (BE), and blood glucose concentration measured before
      asphyxial CA and 1 h after resuscitation. Neurological deficit score (NDS) was
      measured at 12, 24, 48, and 72 h after CA. Histopathologic changes in the
      hippocampal region were observed by H&E staining and histopathologic damage
      score. Ultrastructural morphology was observed by transmission electron
      microscopy. HIF-1 and VEGF expression were measured by immunostaining of serial
      sections obtained from brain tissue. RESULTS: Asphyxial CA -induced global
      cerebral ischemic decreased PaO(2), pH, BE and increased PaCO(2), blood glucose.
      Dexmedetomidine preconditioning improved neurologic outcome, which was associated
      with reduction in histopathologic injury measured by H&E staining, the
      histopathologic damage score and electron microscopy. Dexmedetomidine
      preconditioning also elevated HIF-1alpha and VEGF expression after global
      cerebral ischemia following asphyxial CA. CONCLUSION: Dexmedetomidine
      preconditioning protected against cerebral ischemic injury and was associated
      with upregulation of HIF-1alpha and VEGF expression.

PMID- 25565377
TI  - Proteins and amino acids are fundamental to optimal nutrition support in
      critically ill patients.
AB  - Proteins and amino acids are widely considered to be subcomponents in nutritional
      support. However, proteins and amino acids are fundamental to recovery and
      survival, not only for their ability to preserve active tissue (protein) mass but
      also for a variety of other functions. Understanding the optimal amount of
      protein intake during nutritional support is therefore fundamental to appropriate
      clinical care. Although the body adapts in some ways to starvation, metabolic
      stress in patients causes increased protein turnover and loss of lean body mass.
      In this review, we present the growing scientific evidence showing the importance
      of protein and amino acid provision in nutritional support and their impact on
      preservation of muscle mass and patient outcomes. Studies identifying optimal
      dosing for proteins and amino acids are not currently available. We discuss the
      challenges physicians face in administering the optimal amount of protein and
      amino acids. We present protein-related nutrition concepts, including adaptation
      to starvation and stress, anabolic resistance, and potential adverse effects of
      amino acid provision. We describe the methods for assessment of protein status,
      and outcomes related to protein nutritional support for critically ill patients.
      The identification of a protein target for individual critically ill patients is
      crucial for outcomes, particularly for specific subpopulations, such as obese and
      older patients. Additional research is urgently needed to address these issues. 

PMID- 25565381
TI  - Greatly enlarged thickened gallbladder. Diagnosis: Xanthogranulomatous
      cholecystitis (XGC).

PMID- 25565382
TI  - In vitro evaluation of the acetabular cup primary stability by impact analysis.
AB  - The implant primary stability of the acetabular cup (AC) is an important
      parameter for the surgical success of press-fit procedures used for the insertion
      of cementless hip prostheses. In previous studies by our group (Mathieu, V.,
      Michel, A., Lachaniette, C. H. F., Poignard, A., Hernigou, P., Allain, J., and
      Haiat, G., 2013, "Variation of the Impact Duration During the in vitro Insertion
      of Acetabular Cup Implants," Med. Eng. Phys., 35(11), pp. 1558-1563) and (Michel,
      A., Bosc, R., Mathieu, V., Hernigou, P., and Haiat, G., 2014, "Monitoring the
      Press-Fit Insertion of an Acetabular Cup by Impact Measurements: Influence of
      Bone Abrasion," Proc. Inst. Mech. Eng., Part H, 228(10), pp. 1027-1034), the
      impact momentum and duration were shown to carry information on the press-fit
      insertion of the AC within bone tissue. The aim of the present study is to relate
      the impact momentum recorded during the AC insertion to the AC biomechanical
      primary stability. The experimental protocol consisted in testing 13 bovine bone
      samples that underwent successively series of 15 reproducible mass falls impacts
      (5 kg, 5 cm) followed by tangential stability testing. Each bone sample was
      tested with different hole sizes in order to obtain different stability
      configurations. The impact momentum and the tangential primary stability reach a
      maximum value for an interference fit equal to around 1 mm. Moreover, a
      correlation between the impact momentum and the stability was obtained with all
      samples and all configuration (R2 = 0.65). The implant primary stability can be
      assessed through the measurement of the impact force signal analysis. This study
      opens new paths for the development of a medical device which could be used as a
      decision support system to assist the surgeon during the insertion of the AC
      implant. 

PMID- 25565384
TI  - Copper-mediated dimerization to access 3a,3a'-bispyrrolidinoindoline:
      diastereoselective synthesis of (+)-WIN 64821 and (-)-ditryptophenaline.
AB  - A copper-mediated cyclization and dimerization of tryptamine or tryptophan was
      developed to generate a C2-symmetry C3(sp(3))-C3(sp(3)) bridge with two
      contiguous stereogenic quaternary carbons in one step. Impressively, the ratio
      between exo and endo cyclization products varies when different protecting groups
      of Nb are utilized. This dimerization reaction could be conducted in gram scale.
      With this dimerization method, both endocyclotryptophan (+)-WIN 64821 and
      exocyclotryptophan (-)-ditryptophenaline were synthesized in 5 steps. 

PMID- 25565383
TI  - Specialist-led diabetes registries and predictors of poor glycemic control in
      type 2 diabetes: Insights into the functionally refractory patient from the LMC
      Diabetes Registry database.
AB  - BACKGROUND: The aim of the present study was to explore features associated with
      glycemic control in type 2 diabetes (T2D) patients undergoing care by specialist
      clinics. METHODS: Literature searches identified diabetes registries whose
      databases recorded outcomes of specialist care. The LMC Diabetes Registry
      database (n = 58 280; LMC) was queried to identify patients with T2D who had been
      seen in a defined 14-month period. Logistic regression modeling was used to
      identify predictors of glycemic control in these patients. Poor glycemic control
      was defined as HbA1c >=9.0% (75 mmol/mol) despite specialist care for >=1 year.
      RESULTS: Few published registry-based studies have discussed glycemic control and
      outcomes of specialist care for T2D. Among 10 590 LMC patients with T2D, mean
      HbA1c was 7.6% (60 mmol/mol), with 38% of patients meeting the Canadian Diabetes
      Association target of <=7.0% (53 mmol/mol). Overall, 15% showed poor glycemic
      control with persistent HbA1c >=9.0% (75 mmol/mol); among insulin-treated
      patients (n = 3856), 28% met this criterion. Patient characteristics
      independently associated with poor glycemic control included early age of onset,
      the number of diabetes education program visits, the number of oral therapies,
      and insulin use. CONCLUSIONS: Type 2 diabetes patients with poor glycemic control
      are found disproportionately in referral specialist care clinics. These
      functionally refractory patients demonstrate features that may assist in
      predicting their potential outcome, and may represent a group with specific
      barriers to care. Specialist patient registries, such as the LMC Diabetes
      Registry, may provide critical information regarding this cohort.

PMID- 25565385
TI  - Impact of thrombophilic genes mutations on thrombosis risk in Egyptian
      nonmetastatic cancer patients.
AB  - Venous thromboembolism (VTE) is a common complication in cancer patients. Several
      genetic risk factors related to thrombophilia are known; however, their
      contributions to thrombotic tendency in cancer patients have conflicting results.
      We aimed to determine the prevalence of factor V Leiden (FVL), prothrombin (PTH)
      G20210A and methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphisms
      in Egyptian nonmetastatic cancer patients and their influence on thrombosis risk
      in those patients. Factor V Leiden, PTH G20210A and MTHFR C677T polymorphisms
      were detected in 40 cancer patients with VTE (group 1) and 40 cancer patients
      with no evidence of VTE (group 2) by PCR-based DNA analysis. Factor V and MTHFR
      mutations were higher in group 1 than in group 2 (factor V heterozygous mutation:
      20 vs. 7.5%, homozygous mutation: 10 vs. 2.5%; MTHFR heterozygous mutation: 40
      vs. 25%, homozygous mutation 5 vs. 0%, respectively) (P = 0.03). Mortality rate
      was higher in group 1 (75%) than in group 2 (25%; P < 0.001). No difference was
      found between those groups regarding PTH mutation (P = 1). Mortality rate was
      higher in the presence of homozygous and heterozygous factor V mutation (100 and
      82%, respectively) compared to the wild type (41%) (P = 0.0006). Having any of
      the three studied gene mutations worsened the overall survival (P = 0.0003). Cox
      regression proved that both thrombosis and presence of factor V mutation are
      independent factors affecting survival in cancer patients (P < 0.001 and P =
      0.01, respectively). In conclusion, there is an association between factor V and
      MTHFR mutations and risk of VTE in Egyptian cancer patients. Thrombosis and
      presence of factor V mutation are independent factors that influence survival in
      those patients.

PMID- 25565386
TI  - Microarray-based analysis of gene expression in lycopersicon esculentum seedling
      roots in response to cadmium, chromium, mercury, and lead.
AB  - The effects of heavy metals in agricultural soils have received special attention
      due to their potential for accumulation in crops, which can affect species at all
      trophic levels. Therefore, there is a critical need for reliable bioassays for
      assessing risk levels due to heavy metals in agricultural soil. In the present
      study, we used microarrays to investigate changes in gene expression of
      Lycopersicon esculentum in response to Cd-, Cr-, Hg-, or Pb-spiked soil. Exposure
      to (1)/10 median lethal concentrations (LC50) of Cd, Cr, Hg, or Pb for 7 days
      resulted in expression changes in 29 Cd-specific, 58 Cr-specific, 192 Hg-specific
      and 864 Pb-specific genes as determined by microarray analysis, whereas
      conventional morphological and physiological bioassays did not reveal any
      toxicant stresses. Hierarchical clustering analysis showed that the
      characteristic gene expression profiles induced by Cd, Cr, Hg, and Pb were
      distinct from not only the control but also one another. Furthermore, a total of
      three genes related to "ion transport" for Cd, 14 genes related to "external
      encapsulating structure organization", "reproductive developmental process",
      "lipid metabolic process" and "response to stimulus" for Cr, 11 genes related to
      "cellular metabolic process" and "cellular response to stimulus" for Hg, 78 genes
      related to 20 biological processes (e.g., DNA metabolic process, monosaccharide
      catabolic process, cell division) for Pb were identified and selected as their
      potential biomarkers. These findings demonstrated that microarray-based analysis
      of Lycopersicon esculentum was a sensitive tool for the early detection of
      potential toxicity of heavy metals in agricultural soil, as well as an effective
      tool for identifying the heavy metal-specific genes, which should be useful for
      assessing risk levels due to heavy metals in agricultural soil. 

PMID- 25565387
TI  - Reply to Sham procedure inadequate.

PMID- 25565388
TI  - Hypothalamic-pituitary-adrenal axis functioning in Huntington's disease and its
      association with depressive symptoms and suicidality.
AB  - Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been reported
      in Huntington's disease (HD). In non-HD populations, alterations in HPA axis
      activity have been associated with depression and suicidality. The present study
      aims to compare HPA axis activity between HD mutation carriers and controls, and
      examine its association with depressive symptoms and suicidality. To this end,
      salivary cortisol concentrations at seven time points, as well as depressive
      symptoms and suicidality, were assessed in 49 pre-motor, 102 motor symptomatic
      mutation carriers and 55 controls, at baseline and follow-up combined.
      Differences in parameters of HPA axis activity between these three groups, and
      their associations with depressive symptoms and suicidality in HD mutation
      carriers, were analysed using multilevel regression analyses. There were no
      differences in parameters of HPA axis activity between mutation carriers and
      controls, whereas pre-motor symptomatic mutation carriers had a significantly
      higher area under the curve to the increase (AUCi ) compared to motor symptomatic
      mutation carriers. In the entire HD cohort, HPA axis activity was not associated
      with depressive symptoms or suicidality. After stratifying mutation carriers into
      pre-motor, early and advanced disease stages, beta values differed between these
      groups. Remarkably, a higher AUCi was significantly associated with depressive
      symptoms in pre-motor and early disease stage mutation carriers, with a reverse
      nonsignificant association in advanced disease stage mutation carriers. The lower
      AUCi in motor symptomatic mutation carriers and the varying associations with
      depressive symptoms and suicidality in pre-motor, early and advanced disease
      stages could possibly be explained by exhaustion of the HPA axis after prolonged
      stress-induced HPA axis hyperactivity and deserves further longitudinal study. 

PMID- 25565390
TI  - Acute rhabdomyolysis in a patient with long-term exposure to intrathecal
      ziconotide: a case report.
AB  - INTRODUCTION: Ziconotide is an intrathecally administered nonopioid analgesic for
      the treatment of severe chronic pain. Previous reports have noted rhabdomyolysis
      in patients receiving ziconotide during the initial single-shot trial or due to
      concurrent medical problems. We present a case of an acute rhabdomyolysis
      following an intrathecal bolus injection of ziconotide on a patient who had long
      term exposure to the drug. CASE REPORT: The patient suffered from chronic
      neuropathic pain with diagnosis of failed back surgery syndrome and received
      intrathecal ziconotide for 2 years. Moderate side effects resulting from dose
      escalation led to a discontinuation of the drug. The pump medication was changed
      to morphine, which failed to provide adequate analgesia even with dose titration.
      A single intrathecal bolus of ziconotide, as an adjunctive therapy, resulted in
      good pain control. Two months later, the patient received a second ziconotide
      injection. Sixteen hours after the injection, she presented to local emergency
      center with nausea, vomiting, diarrhea, and myalgia. She had significantly
      increased CK levels and was admitted for intravenous hydration and close
      observation. Her serum CK level peaked at 4940 IU/L. The patient was discharged
      on hospital day 3 with a CK level of 808 IU/L. Her symptoms resolved without
      renal impairment. DISCUSSION: The clinical scenario described is a case of acute
      rhabdomyolysis from an intrathecal bolus injection of ziconotide in a patient
      with prior long-term exposure to the drug. The decrease in CK levels coincided
      well with the average half-life of ziconotide; however, the rhabdomyolysis may
      have been potentiated by hypokalemia.

PMID- 25565389
TI  - A cytosolic juxtamembrane interface modulates plexin A3 oligomerization and
      signal transduction.
AB  - Plexins (plxns) are transmembrane (TM) receptors involved in the guidance of
      vascular, lymphatic vessel, and neuron growth as well as cancer metastasis. Plxn
      signaling results in cytosolic GTPase-activating protein activity, and previous
      research implicates dimerization as important for activation of plxn signaling.
      Purified, soluble plxn extracellular and cytosolic domains exhibit only weak
      homomeric interactions, suggesting a role for the plxn TM and juxtamembrane
      regions in homooligomerization. In this study, we consider a heptad repeat in the
      Danio rerio PlxnA3 cytosolic juxtamembrane domain (JM) for its ability to
      influence PlxnA3 homooligomerization in TM-domain containing constructs. Site
      directed mutagenesis in conjunction with the AraTM assay and bioluminescent
      energy transfer (BRET2) suggest an interface involving a JM heptad repeat, in
      particular residue M1281, regulates PlxnA3 homomeric interactions when examined
      in constructs containing an ectodomain, TM and JM domain. In the presence of a
      neuropilin-2a co-receptor and semaphorin 3F ligand, disruption to PlxnA3
      homodimerization caused by an M1281F mutation is eliminated, suggesting
      destabilization of the PlxnA3 homodimer in the JM is not sufficient to disrupt co
      receptor complex formation. In contrast, enhanced homodimerization of PlxnA3
      caused by mutation M1281L remains even in the presence of ligand semaphorin 3F
      and co-receptor neuropilin-2a. Consistent with this pattern of PlxnA3
      dimerization in the presence of ligand and co-receptor, destabilizing mutations
      to PlxnA3 homodimerization (M1281F) are able to rescue motor patterning defects
      in sidetracked zebrafish embryos, whereas mutations that enhance PlxnA3
      homodimerization (M1281L) are not. Collectively, our results indicate the JM
      heptad repeat, in particular residue M1281, forms a switchable interface that
      modulates both PlxnA3 homomeric interactions and signal transduction. 

PMID- 25565391
TI  - Immune system-related differentially expressed genes, transcription factors and
      microRNAs in post-menopausal females with osteopenia.
AB  - This study was to identify differentially expressed genes (DEGs) in post
      menopausal females with osteopenia and further screened the potentially involved
      transcription factors (TFs) and microRNAs (miRNAs). Data set GSE13850 of
      circulating B lymphocytes from post-menopausal females with low or high bone
      mineral density (BMD) was downloaded from Gene Expression Omnibus. Limma package
      in R was used to identify DEGs following raw data processing. Enrichment analysis
      was performed using DAVID (Database for Annotation, Visualization and Integrated
      Discovery) and visualized using plug-in EnrichmentMap of Cytoscape software. The
      TFs of DEGs were screened using UCSC (University of California, Santa Cruz)
      Genome Browser, and miRNAs targeting DEGs were predicted using TarBase,
      TargetScan and miRecord databases, followed by constructing regulatory networks
      using Cytoscape software. Totally 52 DEGs were obtained from post-menopausal
      females with low BMD compared with those with high BMD. Those DEGs including IL
      4R, IL-2RG, TGF-beta1 and CD74 were mostly related to functions associated with
      immune response, lymphocyte activation, T cell differentiation, leucocyte
      activation and immune system process. NFAT, NF-kappaB and EGR family members
      might have a regulatory effect on these DEGs. PAX5 could regulate 15 DEGs
      including ZFP36L2 and KLF13. Abundant miRNAs were also found to target
      dysregulated ZFP36L2 and KLF13. Dysregulated IL-4R, IL-2RG, TGF-beta1 and CD74
      may mediate the interplay of immune changes and oestrogen deficiency-induced
      osteopenia, and disorder functions of NF-kappaB, NFAT and EGR family members.
      PAX5 and various miRNAs might exert regulatory effect on osteopenia via targeting
      ZFP36L2 and KLF13. 

PMID- 25565393
TI  - Is further screening of men with baseline PSA < 1 ng ml(-1) worthwhile? The
      discussion continues-Results of the Swiss ERSPC (Aarau).
AB  - Recent studies indicate frequent early PSA retesting unrelated of men's baseline
      PSA, which increases the harms of early detection especially among men with low
      PSA. The current study investigates the PCa incidence among men with baseline PSA
      <1.0 ng ml(-1) in order to adjust retest intervals for more targeted early
      detection. Between 1998 and 2012, 2,416 men with baseline PSA <1.0 ng ml(-1) were
      prospectively observed. Primary endpoint was PCa diagnosis. Negative predictive
      value (NPV) and number needed to screen (NNS) to detect one PCa were calculated.
      During a median follow-up time of 12.1 years, 54 (2.2%) PCa were diagnosed with n
      = 26 (48.1%) among men with baseline PSA of 0.75 <= 1.0 ng ml(-1) (upper baseline
      PSA quartile). The 10-year probability of being diagnosed with PCa increased
      significantly from 0.19% (baseline PSA < 0.40 ng ml(-1) ) to 2.0% (baseline PSA
      0.40 <= 0.56 ng ml(-1) ), 2.5% (baseline PSA 0.56 <= 0.75 ng ml(-1) ) over 4.4%
      (baseline PSA 0.75 <= 1.0 ng ml(-1) ) (all p values <0.0001), respectively. The
      frequency of Gleason >=7 PCa increased from 1 (0.17%) to 8 (1.4%), 5 (0.8) over
      11 (1.8%) in these groups. The 8-year NPV for Gleason >= 7 PCa were 99.8
      (baseline PSA < 0.40 ng ml(-1) ), 99.8 (baseline PSA 0.40 <= 0.56 ng ml(-1) ),
      100 (baseline PSA 0.56 <= 0.75 ng ml(-1) ) and 99.5 (baseline PSA 0.75 <= 1.0 ng
      ml(-1) ), respectively. During 12 years, the numbers were 99.8, 98.6, 99.2, and
      98.2, respectively. Therefore, due to the very low rate of Gleason >= 7 PCa,
      further screening might be omitted in men with baseline PSA < 0.4 ng ml(-1) .
      Between 0.4 and 1.0 ng ml(-1) , an 8-year interval can be discussed.

PMID- 25565392
TI  - Neuroanatomical basis of paroxysmal sympathetic hyperactivity: a diffusion tensor
      imaging analysis.
AB  - PRIMARY OBJECTIVE: Paroxysmal sympathetic hyperactivity (PSH) is observed in a
      sub-set of patients with moderate-to-severe traumatic brain injury (TBI). The
      neuroanatomical basis of PSH is poorly understood. It is hypothesized that PSH is
      linked to changes in connectivity within the central autonomic network. RESEARCH
      DESIGN: Retrospective analysis in a sub-set of patients from a multi-centre,
      prospective cohort study Methods and procedures: Adult patients who were <3 weeks
      after severe TBI were enrolled and screened for PSH using a standard definition.
      Patients underwent multimodal MRI, which included quantitative diffusion tensor
      imaging. MAIN OUTCOMES AND RESULTS: Principal component analysis (PCA) was used
      to resolve the set of tracts into components. Ability to predict PSH was
      evaluated via area under the receiver operating characteristic (AUROC) and tree
      based classification analyses. Among 102 enrolled patients, 16 met criteria for
      PSH. The first principle component was significantly associated (p = 0.024, AUROC
      = 0.867) with PSH status even after controlling for age and admission GCS. In a
      classification tree analysis, age, GCS and decreased FA in the splenium of the
      corpus callosum and in the right posterior limb of the internal capsule
      discriminated PSH vs no PSH with an AUROC of 0.933. CONCLUSIONS: Disconnection
      involving the posterior corpus callosum and of the posterior limb of the internal
      capsule may play a role in the pathogenesis or expression of PSH.

PMID- 25565394
TI  - Characteristics of unintentional movements by a multijoint effector.
AB  - The authors explored the phenomenon of unintentional changes in the equilibrium
      state of a multijoint effector produced by transient changes in the external
      force. The subjects performed a position-holding task against a constant force
      produced by a robot and were instructed not to intervene voluntarily with
      movements produced by changes in the robot force. The robot produced a smooth
      force increase leading to a hand movement, followed by a dwell time. Then, the
      force dropped to its initial value leading to hand movement toward the initial
      position, but the hand stopped short of the initial position. The undershoot
      magnitude increased linearly with the peak hand displacement and exponentially
      with dwell time (time constant of about 1 s). For long dwell times, the hand
      stopped at about half the total distance to the initial position. The authors
      interpret the results as consequences of a drift of the referent hand coordinate.
      Our results provide support for back-coupling between the referent and actual
      body configurations during multijoint actions and produce the first quantitative
      analysis of this phenomenon. This mechanism can also explain the phenomena of
      slacking and force drop after turning visual feedback off during accurate force
      production task.

PMID- 25565395
TI  - Dietary patterns in relation to stroke among Iranians: a case-control study.
AB  - BACKGROUND: Although several studies have linked dietary patterns to the risk of
      stroke in Western countries, we are aware of no report in Middle Eastern
      populations with regard to this association. OBJECTIVE: The aim of this study was
      to examine the association between major dietary patterns and risk of stroke
      among a group of Iranian population. METHODS: In a hospital-based case-control
      study, 195 stroke patients, hospitalized in Alzahra University Hospital in 2008,
      were selected as cases and 195 control subjects from patients hospitalized in
      orthopedic or surgical wards with no history of cerebrovascular diseases or
      neurologic disorders were recruited. Usual dietary intakes of participants were
      assessed by means of a validated 168-item semiquantitative food frequency
      questionnaire. To identify major dietary patterns, principal component analysis
      was used and each participant received a factor score for each identified
      pattern. RESULTS: We identified 3 major dietary patterns: high carbohydrate-low
      fat dietary pattern, sweet-fatty dietary pattern, and traditional dietary
      pattern. Those in the highest quartile of traditional dietary pattern were 4.48
      times more likely to have stroke compared to those in the lowest quartile. After
      adjustment for confounders, the association was attenuated. A significant
      association between high carbohydrate-low fat dietary pattern and stroke was also
      observed after controlling for potential confounding factors (odds ratio = 2.19,
      95% confidence interval, 1.08-4.44). Consumption in the sweet-fatty food pattern
      was not associated with the risk of stroke either in crude or in adjusted models.
      CONCLUSION: Major dietary patterns identified by principal components analysis
      are significantly associated with stroke in a Middle Eastern population.

PMID- 25565396
TI  - A phonon scattering bottleneck for carrier cooling in lead chalcogenide
      nanocrystals.
AB  - The cooling dynamics of hot charge carriers in colloidal lead chalcogenide
      nanocrystals is studied by hyperspectral transient absorption spectroscopy. We
      demonstrate a transient accumulation of charge carriers at a high energy critical
      point in the Brillouin zone. Using a theoretical study of the cooling rate in
      lead chalcogenides, we attribute this slowing down of charge carrier cooling to a
      phonon scattering bottleneck around this critical point. The relevance of this
      observation for the possible harvesting of the excess energy of hot carriers by
      schemes such as multiexciton generation is discussed. 

PMID- 25565398
TI  - A nationwide telepathology consultation and quality control program in China:
      implementation and result analysis.
AB  - BACKGROUND: Telepathology may play an important role in pathology consultation
      and quality control for cancer diagnosis in China, as the country has the largest
      population of cancer patients worldwide. In 2011, the Pathology Quality Control
      Center of China and Ministry of Health developed and implemented a nationwide
      telepathology consultation and quality control program for cancer diagnosis in
      China. We here report the results of the two-year implementation and experiences.
      METHODS: the program built an Internet based telepathology platform to connect
      participating hospitals and expert consultants. The hardware and software used
      for the platform were validated in previous validation studies in China. The
      program had three regional centers consisting of Peking Union Medical College,
      Huasi Medical College of Sichuan and 2nd affiliated hospital of Zhejiang
      University. It also had 20 provincial consultation centers based in the
      provincial referral hospitals. 80 provincial or national pathologists served as
      expert consultants for the program, providing telepathology consultation for
      cancer diagnosis for more than 60 participating hospitals. RESULTS: from 2011 to
      July 2013, 16,247 pathology cases were submitted to the platform for
      consultation. Among them, 84% were due to diagnostic difficulty and 16% were due
      to request by patients. The preliminary diagnosis provided by submitting
      pathologists were in agreement with expert opinion in 59.8% of cases but was in
      disagreement with expert opinion in 24.2% of cases. 16.0% of cases were not
      provided with preliminary diagnosis. The distribution of pathology cases by
      system or organ were: digestive system, 17.3%; gynecologic system, 16.7%; head
      and neck, 15.7%; bone and soft tissue, 10.4%; lung and mediastinum, 8.6%; breast,
      7.6%; urinary system, 7.5%; hematopathology, 6.4%; skin, 5.2%; neuropathology,
      2.5% and cytopathology, 1.3%. Expert consultants also provided assessment of
      quality of slide preparation and staining, online lectures and guidance for
      pathology quality control. CONCLUSION: our results of two years' implementation
      indicated that telepathology could solve the problem of uneven distribution of
      pathology resources and provide a solution for countrywide pathology quality
      control in China. Telepathology could play an important role in improving
      pathology diagnosis in China.

PMID- 25565397
TI  - Thiol redox chemistry: role of protein cysteine oxidation and altered redox
      homeostasis in allergic inflammation and asthma.
AB  - Asthma is a pulmonary disorder, with an estimated 300 million people affected
      worldwide. While it is thought that endogenous reactive oxygen species (ROS) and
      reactive nitrogen species (RNS) such as hydrogen peroxide and nitric oxide, are
      important mediators of natural physiological processes, inflammatory cells
      recruited to the asthmatic airways have an exceptional capacity for producing a
      variety of highly reactive ROS and RNS believed to contribute to tissue damage
      and chronic airways inflammation. Antioxidant defense systems form a tightly
      regulated network that maintains the redox environment of the intra- as well as
      extracellular environment. Evidence for an oxidant-antioxidant imbalance in
      asthmatic airways is demonstrated in a number of studies, revealing decreased
      total antioxidant capacity as well as lower levels of individual antioxidants.
      Thiols in the form of GSH and sulfhydryl groups of proteins are among the most
      susceptible oxidant-sensitive targets, and hence, studies investigating protein
      thiol redox modifications in biology and disease have emerged. This perspective
      offers an overview of the combined efforts aimed at the elucidation of mechanisms
      whereby cysteine oxidations contribute to chronic inflammation and asthma, as
      well as insights into potential cysteine thiol-based therapeutic strategies.

PMID- 25565399
TI  - 4-Methylbenzylidene camphor microspheres: reconstituted epidermis (Skinethic(r))
      permeation and distribution.
AB  - OBJECTIVE: The UV filter 3(4-methylbenzylidene) camphor (4-MBC) is a common
      ingredient in sunscreen cosmetic products. However, different 'in vitro' and 'in
      vivo' studies suggest that 4-MBC can cause endocrine disrupting effects.
      Therefore, there is a need for new systems able to minimize the skin penetration
      of this UV filter. The aim of this study was to evaluate cutaneous permeation and
      distribution, through and into EPISKIN reconstituted epidermis (RE) from an O/W
      emulsion containing 4-MBC free or encapsulated in polymeric substantive
      microspheres. METHODS: Microspheres containing 4-MBC were prepared using the
      emulsification-solvent evaporation method and characterized for shape and surface
      morphology and encapsulation efficiency. O/A emulsions containing sunscreen free
      or encapsulated in microspheres were undergone to permeation tests through RE
      using vertical diffusion cells. At the end of the in vitro permeation
      experiments, the skin was subjected to tape stripping procedure to separate
      stratum corneum from viable epidermis. Each part was properly treated to extract
      the sunscreen retained and subject to quantitative analysis. RESULTS: The
      encapsulation of the sunscreen in the microspheres remarkably reduced the
      permeation of 4-MBC and increased its retention on the skin surface where its
      action is more desirable. CONCLUSIONS: The results of this study confirm the
      validity of substantive microspheres as an ideal formulation candidate to use in
      sunscreen preparation as they appear minimizing its systemic uptake and the
      potential associate toxicological risks. Therefore, more of the active sunscreen
      remains on the surface of the skin where it is intended to act and a higher
      activity it will explicate.

PMID- 25565401
TI  - Forkhead box G1 gene haploinsufficiency: an emerging cause of dyskinetic
      encephalopathy of infancy.
AB  - BACKGROUND: 14q12 deletions, including the Forkhead Box G1 (FOXG1) gene and point
      mutations of this gene, are associated with a complex encephalopathy described as
      a congenital variant of Rett syndrome. A mixture of jerks, athetosis, chorea, and
      dystonia is observed early in life in many patients. The aim of this article is
      to report on the spectrum of movement disorders associated with FOXG1
      haploinsufficiency, as described in the literature. PATIENTS AND METHODS: We
      provide a review of the cases reported in the literature, adding two new
      patients. We searched for a comprehensive set of clinical features, including age
      at onset and semiology of the movement disorder, occurrence and type of
      stereotypies, and neurological outcome. RESULTS: A total of 51 cases were
      included in our study. Nonepileptic abnormal movements occurred in 33 cases,
      often variably combined and presenting during the first year of life. CONCLUSION:
      The neurological phenotype of FOXG1 haploinsufficiency shows the features of a
      dyskinetic encephalopathy of infancy.

PMID- 25565400
TI  - Decarbamoyl mitomycin C (DMC) activates p53-independent ataxia telangiectasia and
      rad3 related protein (ATR) chromatin eviction.
AB  - Interstrand crosslinks induce DNA replication fork stalling that in turn
      activates the ATR-dependent checkpoint and DNA repair on nuclear chromatin.
      Mitomycin C (MC) and Decarbamoyl Mitomycin C (DMC) induce different types of DNA
      crosslinks with DMC being a more cytotoxic agent. We previously reported that the
      novel DMC induced beta-interstrand DNA crosslinks induce a p53-independent form
      of cell death. The p53-independent DMC cytotoxicity associates with the
      activation, and subsequent depletion, of Chk1. In this study we further dissect
      the novel DMC signal transduction pathway and asked how it influences chromatin
      associated proteins. We found that treatment with DMC, but not MC, stimulated the
      disassociation of ATR from chromatin and re-localization of ATR to the cytoplasm.
      The chromatin eviction of ATR was coupled with the formation of nuclear Rad51
      foci and the phosphorylation of Chk1. Furthermore, DMC but not MC, activated
      expression of gadd45alpha mRNA. Importantly, knocking down p53 via shRNA did not
      inhibit the DMC-induced disassociation of ATR from chromatin or reduce the
      activation of transcription of gadd45alpha. Our results suggest that DMC induces
      a p53-independent disassociation of ATR from chromatin that facilitates Chk1
      checkpoint activation and Rad51 chromatin recruitment. Our findings provide
      evidence that ATR chromatin eviction in breast cancer cells is an area of study
      that should be focused on for inducing p53-independent cell death. 

PMID- 25565403
TI  - A nanoparticle catalyst for heterogeneous phase para-hydrogen-induced
      polarization in water.
AB  - Para-hydrogen-induced polarization (PHIP) is a technique capable of producing
      spin polarization at a magnitude far greater than state-of-the-art magnets. A
      significant application of PHIP is to generate contrast agents for biomedical
      imaging. Clinically viable and effective contrast agents not only require high
      levels of polarization but heterogeneous catalysts that can be used in water to
      eliminate the toxicity impact. Herein, we demonstrate the use of Pt nanoparticles
      capped with glutathione to induce heterogeneous PHIP in water. The ligand
      inhibited surface diffusion on the nanoparticles resulted in a (1) H polarization
      of P=0.25% for hydroxyethyl propionate, a known contrast agent for magnetic
      resonance angiography. Transferring the (1) H polarization to a (13) C nucleus
      using a para-hydrogen polarizer yielded a polarization of 0.013%. The nuclear
      spin polarizations achieved in these experiments are the first reported to date
      involving heterogeneous reactions in water.

PMID- 25565402
TI  - Sleep and nighttime energy consumption in early childhood: a population-based
      cohort study.
AB  - BACKGROUND: Shorter sleep is a risk factor for weight gain in young children.
      Experimental studies show that sleep deprivation is associated with higher
      nighttime energy intake, but no studies have examined the patterning of energy
      intake in relation to nighttime sleep duration in young children. OBJECTIVES: The
      objectives of the study were to test the hypothesis that shorter-sleeping
      children would show higher nighttime energy intake and to examine whether the
      additional calories were from drinks, snacks or meals. METHODS: Participants were
      1278 families from the Gemini twin cohort, using data from one child per family
      selected at random to avoid clustering effects. Nighttime sleep duration was
      measured at 16 months of age using the Brief Infant Sleep Questionnaire. Energy
      intake by time of day and eating episode (meal, snack, drink) were derived from 3
      day diet diaries completed when children were 21 months. RESULTS: Consistent with
      our hypothesis, shorter-sleeping children consumed more calories at night only
      (linear trend P < 0.001), with those sleeping <10 h consuming on average 120
      calories (15.2% of daily intake) more at night than those sleeping >=13 h. The
      majority of nighttime intake was from milk drinks. Associations remained after
      adjusting for age, sex, birth weight, gestational age, maternal education, weight
      and daytime sleep. CONCLUSIONS: Shorter-sleeping, young children consume more
      calories, predominantly at night, and from milk drinks. Parents should be aware
      that providing milk drinks at night may contribute to excess intake. This
      provides a clear target for intervention that may help address associations
      between sleep and weight observed in later childhood.

PMID- 25565404
TI  - Dulaglutide: the newest GLP-1 receptor agonist for the management of type 2
      diabetes.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of
      the glucagon-like peptide-1 receptor agonist (GLP-1 RA), dulaglutide, in the
      treatment of type 2 diabetes mellitus (T2D). DATA SOURCES: A PubMed search was
      completed to identify publications from 1947 to October 2014 using the search
      terms dulaglutide and LY2189265. References were reviewed to identify additional
      resources. STUDY SELECTION AND DATA EXTRACTION: Articles were included if they
      evaluated the pharmacology, pharmacokinetics, safety, or efficacy of dulaglutide.
      DATA SYNTHESIS: Dulaglutide reduces both glycosylated hemoglobin (A1C) and weight
      by stimulating insulin secretion and suppressing glucagon in a glucose-dependent
      manner, delaying gastric emptying, and promoting satiety. Dulaglutide consists of
      2 GLP-1 analogues that have been modified to make it a long-acting, once-weekly
      agent. Dulaglutide has been studied as monotherapy and in combination with
      metformin, glimepiride, pioglitazone, and insulin lispro. It has demonstrated
      superior A1C reduction compared with placebo, metformin, insulin glargine,
      sitagliptin, and twice-daily exenatide. It demonstrated noninferiority in A1C
      reduction to liraglutide. Dulaglutide changed A1C by -0.78% to -1.51%, and it
      changed weight by -0.35 kg to -3.03 kg. The most common adverse effects in
      clinical studies were nausea, vomiting, and diarrhea. CONCLUSIONS: Dulaglutide is
      the fifth GLP-1 RA approved for T2D in the United States. It is an attractive
      option because it is dosed once-weekly, provides A1C lowering similar to
      liraglutide, weight reduction similar to exenatide, and has an adverse effect
      profile similar to exenatide and liraglutide.

PMID- 25565405
TI  - Characteristics of and risk factors for interstitial lung disease induced by
      chemotherapy for lung cancer.
AB  - BACKGROUND: Drug-induced interstitial lung disease (DILD) is generally a serious
      adverse effect and almost always necessitates the discontinuation of the
      offending drug. Cancer pharmacotherapy is strongly associated with DILD, and the
      risk of DILD has been suggested to be higher in patients with lung cancer because
      of preexisting pneumonic disease. OBJECTIVE: The aim of this retrospective study
      was to identify the risk factors and prognostic factors for early death from
      interstitial lung disease (ILD) induced by chemotherapy for lung cancer. METHODS:
      The medical records of 459 patients who underwent chemotherapy for lung cancer
      between April 2007 and March 2013 were analyzed with regard to patient background
      and DILD development, initial symptoms, and prognosis. RESULTS: A total of 33
      patients (7.2%) developed chemotherapy-induced ILD. The most frequently observed
      initial symptom was dyspnea (94.3%). Preexisting ILD was identified as a risk
      factor for DILD (odds ratio [OR] = 5.38; 95% CI = 2.47-11.73; P < 0.01). Among
      the 33 patients who developed DILD, 10 patients suffered an early death despite
      steroid therapy. Poor prognostic factors included epidermal growth factor
      receptor-tyrosine kinase inhibitor (EGFR-TKI) use (OR = 9.26; 95% CI = 1.05-82.0;
      P < 0.05) and 2 or more prior chemotherapy regimens (OR = 6.95; 95% CI = 1.14
      42.3; P < 0.05). CONCLUSIONS: Many lung cancer patients have coexisting ILD, and
      these patients have a high risk of developing chemotherapy-induced ILD. In
      addition, patients with DILD who underwent EGFR-TKI therapy and 2 or more prior
      chemotherapy regimens had a higher risk of fatal outcome.

PMID- 25565406
TI  - Direct calibration in megavoltage photon beams using Monte Carlo conversion
      factor: validation and clinical implications.
AB  - The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) has
      established a method for ionisation chamber calibrations using megavoltage photon
      reference beams. The new method will reduce the calibration uncertainty compared
      to a (60)Co calibration combined with the TRS-398 energy correction factor. The
      calibration method employs a graphite calorimeter and a Monte Carlo (MC)
      conversion factor to convert the absolute dose to graphite to absorbed dose to
      water. EGSnrc is used to model the linac head and doses in the calorimeter and
      water phantom. The linac model is validated by comparing measured and modelled
      PDDs and profiles. The relative standard uncertainties in the calibration factors
      at the ARPANSA beam qualities were found to be 0.47% at 6 MV, 0.51% at 10 MV and
      0.46% for the 18 MV beam. A comparison with the Bureau International des Poids et
      Mesures (BIPM) as part of the key comparison BIPM.RI(I)-K6 gave results of
      0.9965(55), 0.9924(60) and 0.9932(59) for the 6, 10 and 18 MV beams,
      respectively, with all beams within 1sigma of the participant average. The
      measured kQ values for an NE2571 Farmer chamber were found to be lower than those
      in TRS-398 but are consistent with published measured and modelled values. Users
      can expect a shift in the calibration factor at user energies of an NE2571
      chamber between 0.4-1.1% across the range of calibration energies compared to the
      current calibration method. 

PMID- 25565407
TI  - Cognitive function in older adults according to current socioeconomic status.
AB  - Cognitive function may be influenced by education, socioeconomic status, sex, and
      health status. Furthermore, aging interacts with these factors to influence
      cognition and dementia risk in late life. Factors that may increase or decrease
      successful cognitive aging are of critical importance, particularly if they are
      modifiable. The purpose of this study was to determine if economic status in late
      life is associated with cognition independent of socioeconomic status in early
      life. Cross-sectional demographic, socioeconomic, and cognitive function data
      were obtained in 2592 older adults (average age 71.6 years) from the Center for
      Disease Control's National Health and Nutrition Examination Survey (NHANES) and
      analyzed with linear regression modeling. Cognitive function, as measured with a
      test of processing speed, was significantly associated with poverty index scores
      after adjusting for educational attainment as an estimate of childhood
      socioeconomic status, ethnic background, age, health status, and sex (P < 0.001).
      Our findings suggest that current economic status is independently associated
      with cognitive function in adults over age 60 years.

PMID- 25565408
TI  - Maternal thyroid dysfunction during gestation, preterm delivery, and birthweight.
      The Infancia y Medio Ambiente Cohort, Spain.
AB  - BACKGROUND: Maternal clinical thyroid disorders can cause reproductive
      complications. However, the effects of mild thyroid dysfunctions are not yet well
      established. The aim was to evaluate the association of maternal thyroid function
      during the first half of pregnancy with birthweight and preterm delivery.
      METHODS: We analysed data on 2170 pregnant women and their children from a
      prospective population-based cohort study in four Spanish areas. Mid-gestation
      maternal serum and urine samples were gathered to determine thyroid-stimulating
      hormone (TSH), free thyroxine (fT4 ), and urinary iodine concentration (UIC).
      Thyroid status was defined according to percentile distribution as: euthyroid
      (TSH and fT4 >5th and <95th percentiles); hypothyroxinaemia (fT4  < 5 th
      percentile and TSH normal), hypothyroidism (TSH > 95th percentile and fT4 normal
      or <5th percentile), hyperthyroxinaemia (fT4  > 95 th percentile and TSH normal),
      and hyperthyroidism (TSH < 5 th percentile and fT4 normal or >95th percentile).
      Response variables were birthweight, small and large for gestational age
      (SGA/LGA), and preterm delivery. RESULTS: An inverse association of fT4 and TSH
      with birthweight was found, the former remaining when restricted to euthyroid
      women. High fT4 levels were also associated with an increased risk of SGA [odds
      ratio, 95% confidence interval (CI) 1.28 (95% CI 1.08, 1.51)]. Mean birthweight
      was higher in the hypothyroxinaemic group (beta = 109, P < 0.01). Iodine intake
      and UIC were not associated with birth outcomes. CONCLUSIONS: High maternal fT4
      levels during the first half of pregnancy were related to lower birthweight and
      increased risk of SGA newborns, suggesting that maternal thyroid function may
      affect fetal growth, even within the normal range.

PMID- 25565409
TI  - A Meta-Analytic Multitrait Multirater Separation of Substance and Style in Social
      Desirability Scales.
AB  - Though unlikely virtues scales have a long history in personality, clinical, and
      applied psychology for detecting socially desirable responding, using such social
      desirability (SD) scales has generally failed to improve the validity of
      personality measures. We examined whether this is because (a) response distortion
      itself has minimal impact on personality's validity, (b) SD scales are
      ineffective at assessing response distortion, or (c) SD scales are conflated with
      substantive trait variance. We compiled a meta-analytic multitrait multimethod
      matrix consisting of multirater personality traits, SD scales, and performance
      outcomes. We examined the influence of trait factors and self-report method
      factors on SD scales and performance. We found that self-report method variance
      (a) was negatively related to performance, (b) would suppress personality
      performance relationships for self-report measures, and (c) was (partially)
      assessed by SD scales. However, relative to the effects of self-report method
      variance, SD scales are even more strongly influenced by Conscientiousness,
      Emotional Stability, and Agreeableness. It is not the case that SD scales are
      insensitive to inflated responding but that their susceptibility to personality
      trait variance likely outweighs their benefits. We discuss the implications of
      these results for using SD scales in research and practice.

PMID- 25565410
TI  - Posttraumatic stress disorder and incidence of type 2 diabetes mellitus in a
      sample of women: a 22-year longitudinal study.
AB  - IMPORTANCE: Posttraumatic stress disorder (PTSD) is a common, debilitating mental
      disorder that has been associated with type 2 diabetes mellitus (T2D) and its
      risk factors, including obesity, in cross-sectional studies. If PTSD increases
      risk of incident T2D, enhanced surveillance in high-risk populations may be
      warranted. OBJECTIVE: To conduct one of the first longitudinal studies of PTSD
      and incidence of T2D in a civilian sample of women. DESIGN, SETTING, AND
      PARTICIPANTS: The Nurses' Health Study II, a US longitudinal cohort of women (N =
      49,739). We examined the association between PTSD symptoms and T2D incidence over
      a 22-year follow-up period. MAIN OUTCOMES AND MEASURES: Type 2 diabetes, self
      reported and confirmed with self-report of diagnostic test results, symptoms, and
      medications, a method previously validated by physician medical record review.
      Posttraumatic stress disorder was assessed by the Short Screening Scale for DSM
      IV PTSD. We examined longitudinal assessments of body mass index, smoking,
      alcohol intake, diet quality, physical activity, and antidepressant use as
      mediators of possible increased risk of T2D for women with PTSD. The study
      hypothesis was formulated prior to PTSD ascertainment. RESULTS: Symptoms of PTSD
      were associated in a dose-response fashion with T2D incidence (1-3 symptoms:
      hazard ratio, 1.4 [95% CI, 1.2-1.6]; 4 or 5 symptoms; hazard ratio, 1.5 [95% CI,
      1.3-1.7]; 6 or 7 symptoms: hazard ratio, 1.8 [95% CI, 1.5-2.1]). Antidepressant
      use and a higher body mass index associated with PTSD accounted for nearly half
      of the increased risk of T2D for women with PTSD. Smoking, diet quality, alcohol
      intake, and physical activity did not further account for increased risk of T2D
      for women with PTSD. CONCLUSIONS AND RELEVANCE: Women with the highest number of
      PTSD symptoms had a nearly 2-fold increased risk of T2D over follow-up than women
      with no trauma exposure. Health professionals treating women with PTSD should be
      aware that these patients are at risk of increased body mass index and T2D.
      Comprehensive PTSD treatment should be expanded to address the health behaviors
      that contribute to obesity and chronic disease in affected populations.

PMID- 25565412
TI  - Proteins at interfaces probed by chiral vibrational sum frequency generation
      spectroscopy.
AB  - Characterizations of protein structures at interfaces are important in solving an
      array of fundamental and engineering problems, including understanding
      transmembrane signal transduction and molecular transport processes and
      development of biomaterials to meet the needs of biomedical and energy research.
      However, in situ and real-time characterization of protein secondary structures
      is challenging because it requires physical methods that are selective to both
      interface and secondary structures. Here, we summarize recent experimental
      developments in our laboratory of chiral vibrational sum frequency generation
      spectroscopy (SFG) for analyzing protein structures at interfaces. We showed that
      chiral SFG provides vibrational optical signatures of the peptide N-H stretch and
      amide I modes that can distinguish various protein secondary structures. Using
      these signatures, we further applied chiral SFG to probe orientations and folding
      kinetics of proteins at interfaces. Our results show that chiral SFG is a
      background-free, label-free, in situ, and real-time vibrational method for
      studying proteins at interfaces. This recent progress demonstrates the potential
      of chiral SFG in solving problems related to proteins and other chiral
      biopolymers at interfaces. 

PMID- 25565411
TI  - Reversibly extracellular pH controlled cellular uptake and photothermal therapy
      by PEGylated mixed-charge gold nanostars.
AB  - Shielding nanoparticles from nonspecific interactions with normal cells/tissues
      before they reach and after they leave tumors is crucial for the selective
      delivery of NPs into tumor cells. By utilizing the reversible protonation of weak
      electrolytic groups to pH changes, long-chain amine/carboxyl-terminated
      polyethylene glycol (PEG) decorated gold nanostars (GNSs) are designed,
      exhibiting reversible, significant, and sensitive response in cell affinity and
      therapeutic efficacy to the extracellular pH (pHe) gradient between normal
      tissues and tumors. This smart nanosystem shows good dispersity and unimpaired
      photothermal efficacy in complex bioenvironment at pH 6.4 and 7.4 even when their
      surface charge is neutral. One PEGylated mixed-charge GNSs with certain surface
      composition, GNS-N/C 4, exhibits high cell affinity and therapeutic efficacy at
      pH 6.4, and low affinity and almost "zero" damage to cells at pH 7.4. Remarkably,
      this significant and sensitive response in cell affinity and therapeutic efficacy
      is reversible as local pH alternated. In vivo, GNS-N/C 4 shows higher
      accumulation in tumors and improved photothermal therapeutic efficacy than pH
      insensitive GNSs. This newly developed smart nanosystem, whose cell affinity
      reversibly transforms in response to pHe gradient with unimpaired biostability,
      provides a novel effective means of tumor-selective therapy. 

PMID- 25565414
TI  - Abnormal skin biopsy for intraepidermal nerve fibers: When "Decreased small nerve
      fibers" is not "Small fiber neuropathy".

PMID- 25565413
TI  - The ubiquitous transcription factor CTCF promotes lineage-specific epigenomic
      remodeling and establishment of transcriptional networks driving cell
      differentiation.
AB  - Cell differentiation relies on tissue-specific transcription factors (TFs) that
      cooperate to establish unique transcriptomes and phenotypes. However, the role of
      ubiquitous TFs in these processes remains poorly defined. Recently, we have shown
      that the CCCTC-binding factor (CTCF) is required for adipocyte differentiation
      through epigenomic remodelling of adipose tissue-specific enhancers and
      transcriptional activation of Peroxisome proliferator-activated receptor gamma
      (PPARG), the main driver of the adipogenic program (PPARG), and its target genes.
      Here, we discuss how these findings, together with the recent literature,
      illuminate a functional role for ubiquitous TFs in lineage-determining
      transcriptional networks. 

PMID- 25565415
TI  - Solid-State crystal-to-crystal phase transitions and reversible structure
      temperature behavior of phosphovanadomolybdic acid, H5PV2Mo10O40.
AB  - The crystal packing and secondary structure of H5PV2Mo12O40 was followed by
      careful X-ray diffraction studies that revealed four unique structures and three
      solid phase transitions at temperatures between 25 and 55  degrees C, with loss
      of solvated water and concomitant contraction of the volume and increase of the
      packing density. Above 60  degrees C H5PV2Mo12O40 becomes amorphous and then
      anhydrous although the polyoxometalate cluster is stable indefinitely up to 300 
      degrees C. Above this temperature, combined IR, Raman, XRD, and XPS measurements
      show the decomposition of H5PV2Mo12O40 to crystalline MoO3 and probably amorphous
      vanadium oxide and vanadylphosphate, the latter appearing to cover the surface of
      MoO3. Importantly, H5PV2Mo12O40 can be easily recovered by dissolution in water
      at 80  degrees C. 

PMID- 25565417
TI  - Bioreducible shell-cross-linked hyaluronic acid nanoparticles for tumor-targeted
      drug delivery.
AB  - The major issues of self-assembled nanoparticles as drug carriers for cancer
      therapy include biostability and tumor-targetability because the premature drug
      release from and nonspecific accumulation of the drug-loaded nanoparticles may
      cause undesirable toxicity to normal organs and lower therapeutic efficacy. In
      this study, we developed robust and tumor-targeted nanocarriers based on an
      amphiphilic hyaluronic acid (HA)-polycaprolactone (PCL) block copolymer, in which
      the HA shell was cross-linked via a bioreducible disulfide linkage. Doxorubicin
      (DOX), chosen as a model anticancer drug, was effectively encapsulated into the
      nanoparticles with high drug loading efficiency. The DOX-loaded bioreducible HA
      nanoparticles (DOX-HA-ss-NPs) greatly retarded the drug release under
      physiological conditions (pH 7.4), whereas the drug release rate was markedly
      enhanced in the presence of glutathione, a thiol-containing tripeptide capable of
      reducing disulfide bonds in the cytoplasm. Furthermore, DOX-HA-ss-NPs could
      effectively deliver the DOX into the nuclei of SCC7 cells in vitro as well as to
      tumors in vivo after systemic administration into SCC7 tumor-bearing mice,
      resulting in improved antitumor efficacy in tumor-bearing mice. Overall, it was
      demonstrated that bioreducible shell-cross-linked nanoparticles could be used as
      a potential carrier for cancer therapy. 

PMID- 25565416
TI  - Mobile-Web app to self-manage low back pain: randomized controlled trial.
AB  - BACKGROUND: Nonspecific low back pain (NLBP) is the diagnosis for individuals
      with back pain that has no underlying medical cause (eg, tumor, infection,
      fracture, herniated disc, spinal stenosis). The American College of Physicians
      (ACP) and American Pain Society (APS) recommend multidisciplinary treatments for
      NLBP that lasts more than 4 weeks. This approach, however, is impractical for
      many physicians to implement, and relatively few providers offer NLBP treatment
      that meets the joint ACP-APS guidelines. OBJECTIVE: This study evaluated the
      efficacy of a mobile-Web intervention called "FitBack" to help users implement
      self-tailored strategies to manage and prevent NLBP occurrences. METHODS: A total
      of 597 adults were recruited, screened, consented, and assessed online at
      baseline, at 2 months (T2), and at 4 months (T3). After baseline assessments,
      participants were randomized into three groups: FitBack intervention, alternative
      care group that received 8 emails urging participants to link to six Internet
      resources for NLBP, and control group. The FitBack group also received weekly
      email reminder prompts for 8 weeks plus emails to do assessments. The control
      group was only contacted to do assessments. RESULTS: Users of the FitBack program
      showed greater improvement compared to the control group in every comparison of
      the critical physical, behavioral, and worksite outcome measures at 4-month
      follow-up. In addition, users of the FitBack program performed better than the
      alternative care group on current back pain, behavioral, and worksite outcomes at
      4-month follow-up. For example, subjects in the control group were 1.7 times more
      likely to report current back pain than subjects in the FitBack group; subjects
      in the alternative care group were 1.6 times more likely to report current back
      pain at 4-month follow-up. Further, the users of the FitBack program showed
      greater improvement compared to both the control and alternative care groups at 4
      month follow-up on patient activation, constructs of the Theory of Planned
      Behavior, and attitudes toward pain. CONCLUSIONS: This research demonstrated that
      a theoretically based stand-alone mobile-Web intervention that tailors content to
      users' preferences and interests can be an effective tool in self-management of
      low back pain. When viewed from the RE-AIM perspective (ie, reach,
      efficacy/effectiveness, adoption, implementation fidelity, and maintenance), this
      study supports the notion that there is considerable value in this type of
      intervention as a potentially cost-effective tool that can reach large numbers of
      people. The results are promising considering that the FitBack intervention was
      neither supported by professional caregivers nor integrated within a health
      promotion campaign, which might have provided additional support for
      participants. Still, more research is needed on how self-guided mobile-Web
      interventions will be used over time and to understand factors associated with
      continuing user engagement. TRIAL REGISTRATION: Clinicaltrials.gov NCT01950091;
      http://clinicaltrials.gov/ct2/show/NCT01950091 (Archived by WebCite at
      http://www.webcitation.org/6TwZucX77).

PMID- 25565418
TI  - Effects of "face" consciousness on status consumption among Chinese consumers:
      perceived social value as a mediator.
AB  - Chinese consumers are interested in status consumption, i.e., in striving to
      enhance their social standings through the consumption of luxury products. This
      study investigates how face consciousness, one's social self-esteem, and desire
      to be respected influences status consumption behavior in China. The
      Consciousness of Social Face Scale, the Social Value Scale, and the Status
      Consumption Scale were administered to 192 MBA students from a university in east
      China (117 men, 69 women, 6 unreported sex). The results revealed that face
      consciousness was positively related to Chinese consumers' status consumption.
      Moreover, the results showed that the effects of face consciousness on status
      consumption were partly mediated by consumer social value. The findings highlight
      the importance of face consciousness in understanding Chinese consumer behaviors.

PMID- 25565419
TI  - Risk factors for herpes zoster in rheumatoid arthritis patients: the role of
      tumour necrosis factor-alpha inhibitors.
AB  - AIM: To determine whether exposure to tumour necrosis factor (TNF)-alpha
      inhibitors increases the risk of herpes zoster (HZ) among people with rheumatoid
      arthritis (RA). METHODS: We performed a cohort study of people with RA
      participating in the Australian Rheumatology Association Database. We identified
      self-reported cases of HZ and verified using medical records. For the primary
      analysis, we only included doctor-verified cases. For TNF-alpha inhibitor exposed
      groups, we excluded HZ episodes that occurred before TNF-alpha inhibitor
      initiation, and for the control group we excluded HZ episodes that occurred prior
      to 2000 or RA diagnosis. The risk of HZ among participants exposed versus not
      exposed to TNF-alpha inhibitors was compared using Cox proportional hazards
      models including significant covariates affecting the risk. Adjusted hazard
      ratios (HR) were calculated for TNF inhibitors as a class and for individual
      agents. RESULTS: Among 2157 active RA participants, there were 442 self-reported
      cases of HZ. From 346 responses from doctors, 249 cases were verified and four
      were false positives (false positive rate 1.6%). Crude incidence of verified HZ
      in the entire RA cohort was 15.9/1000 person-years (95% confidence interval (CI):
      13.5-18.8). An increased risk of HZ was found for all TNF-alpha inhibitors
      combined (fully adjusted HR 1.71; 95% CI: 1.00-2.92) and adalimumab (fully
      adjusted HR 2.33; 95% CI: 1.22-4.45), but in the fully adjusted model was not
      increased with etanercept (fully adjusted HR 1.65; 95% CI: 0.90-3.03). No
      increased risk was found with infliximab (HR 1.29; 95% CI: 0.37-4.47).
      CONCLUSIONS: TNF-alpha inhibitors are associated with an increased risk of HZ in
      people with RA compared with those who have not been exposed.

PMID- 25565420
TI  - Microsnare-assisted microcatheter navigation for flow diversion of a challenging
      giant intracerebral aneurysm: a novel technique.
AB  - Giant cerebral aneurysms are associated with a poor prognosis, with 2-year
      survival rates reported as low as 20% (Sundt et al.; Syman et al.). Morbidity is
      largely associated with haemorrhage, local compressive effects and thrombosis.
      While endovascular coiling has been acknowledged as a safe treatment in small to
      medium size aneurysms (Molyneux et al.; Pierot, Spelle & Vitry), the safety of
      this technique is more questionable in giant aneurysms due to the unknown
      stability of the coiling mesh and the need for retreatment. Parent vessel
      remodelling with the use of flow diverters is an evolving technique with
      promising results (Pierot et al.). However, navigation of microcatheters within
      the parent artery across giant aneurysms may be challenging due to tortuous
      anatomy. To improve microcatheter trackability and stability across a giant
      aneurysm neck, we describe a novel microsnare-assisted support technique. 

PMID- 25565421
TI  - The nature of the Fe-graphene interface at the nanometer level.
AB  - The emerging fields of graphene-based magnetic and spintronic devices require a
      deep understanding of the interface between graphene and ferromagnetic metals.
      This paper reports a detailed investigation at the nanometer level of the Fe
      graphene interface carried out by angle-resolved photoemission, high-resolution
      photoemission from core levels, near edge X-ray absorption fine structure,
      scanning tunnelling microscopy and spin polarized density functional theory
      calculations. Quasi-free-standing graphene was grown on Pt(111), and the iron
      film was either deposited atop or intercalated beneath graphene. Calculations and
      experimental results show that iron strongly modifies the graphene band structure
      and lifts its pi band spin degeneracy. 

PMID- 25565422
TI  - Editorial: ChemSusChem volume 8: all aboard!

PMID- 25565426
TI  - BH3-only proteins: a 20-year stock-take.
AB  - BH3-only proteins are the sentinels of cellular stress, and their activation
      commits cells to apoptosis. Since the discovery of the first BH3-only protein BAD
      almost 20 years ago, at least seven more BH3-only proteins have been identified
      in mammals. They are regulated by a variety of environmental stimuli or by
      developmental cues, and play a crucial role in cellular homeostasis. Some are
      considered to be tumor suppressors, and also play a significant role in other
      pathologies. Their non-apoptotic functions are controversial, but there is broad
      consensus emerging regarding their role in apoptosis, which may help in designing
      better therapeutic agents for treating a variety of human diseases. 

PMID- 25565427
TI  - Plateletcrit: a sensitive biomarker for evaluating disease activity in Crohn's
      disease with low hs-CRP.
AB  - OBJECTIVE: This study aimed to investigate whether PLT indices could act as non
      invasive biomarkers for active Crohn's disease (CD). METHODS: Altogether 130 CD
      patients and 130 age- and gender-matched healthy volunteers were retrospectively
      enrolled in the study. CD patients were further divided into patients with active
      disease (Crohn's disease activity index [CDAI] >150) and in remission. PLT
      indices including PLT count, mean platelet volume (MPV), platelet distribution
      width (PDW), platelet large cell ratio (P-LCR) and plateletcrit (PCT) were
      detected. High-sensitivity C-reactive protein (hs-CRP) and erythrocyte
      sedimentation rate (ESR) levels were also determined. RESULTS: In active CD, PLT
      and PCT levels were notably higher but P-LCR and PDW levels were lower than those
      in healthy controls and patients in remission. PLT, PDW, P-LCR and PCT were
      significantly correlated with CDAI (P < 0.05). The receiver operating
      characteristic (ROC) curve showed that with a cut-off value of 0.28%, PCT
      achieved a sensitivity of 67% and a specificity of 63% for detecting active CD,
      with the area under ROC curve (AUROC) of 0.67, which was inferior to hs-CRP and
      ESR. For patients with active disease who had hs-CRP levels lower than 10.0 mg/L,
      PCT turned out to be the best index for monitoring disease activity (sensitivity
      71%, specificity 85%, AUROC 0.77, P = 0.02). CONCLUSION: PCT may act as a
      specific and sensitive biomarker for determining active CD, especially in
      patients with an hs-CRP level lower than 10.0 mg/L.

PMID- 25565428
TI  - Cleaving depressive diseases from depressive disorders and non-clinical states.
AB  - OBJECTIVE: We sought to determine whether putative depressive diseases could be
      differentiated categorically from clinical depressive disorders and non-clinical
      mood states. METHOD: We interviewed volunteers who reported or denied any
      lifetime depressive mood state and analyzed data from the former group reporting
      on their 'most severe' depressive episode. We employed latent class analysis
      (LCA) to determine whether a two-class solution was supported and the
      contribution of individual variables to class allocations. RESULTS: All variables
      were significant predictors of class allocation. LCA-assigned Class I
      participants reported more depressive symptoms, had more distressing episodes and
      more lasting consequences, were more likely to view their depression as 'like a
      disease', and as being both disproportionately more severe and persistent in
      relation to any antecedent stressor. Validation involved comparison of LCA
      assignment with DSM-IV diagnosis for their most severe depressive episode. Of
      those assigned to Class I, 89% had a DSM diagnosis of melancholic, psychotic or
      bipolar depression. Class II had all those failing to meet criteria for a
      depressive episode and the majority of those with a non-melancholic depressive
      condition. CONCLUSION: Despite not including individual depressive symptoms,
      study variables strongly differentiated putative depressive diseases from a
      composite of clinical depressive conditions and subclinical depressive states.

PMID- 25565425
TI  - Powerful Drosophila screens that paved the wingless pathway.
AB  - The Wnt/Wingless (Wg) signaling cascade controls a number of biological processes
      in animal development and adult life; aberrant Wnt/Wg signaling can cause
      diseases. In the 1980s genes were discovered that encode core Wnt/Wg pathway
      components: their mutant phenotypes were similar and an outline of a signaling
      cascade emerged. Over the years our knowledge of this important signaling system
      increased and more components were uncovered that are instrumental for Wnt/Wg
      secretion and transduction. Here we provide an overview of these discoveries, the
      technologies involved, with a particular focus on the important role Drosophila
      screens played in this process. 

PMID- 25565429
TI  - Energetic salts with pi-stacking and hydrogen-bonding interactions lead the way
      to future energetic materials.
AB  - Among energetic materials, there are two significant challenges facing
      researchers: 1) to develop ionic CHNO explosives with higher densities than their
      parent nonionic molecules and (2) to achieve a fine balance between high
      detonation performance and low sensitivity. We report a surprising energetic
      salt, hydroxylammonium 3-dinitromethanide-1,2,4-triazolone, that exhibits
      exceptional properties, viz., higher density, superior detonation performance,
      and improved thermal, impact, and friction stabilities, then those of its
      precursor, 3-dinitromethyl-1,2,4-triazolone. The solid-state structure features
      of the new energetic salt were investigated with X-ray diffraction which showed
      pi-stacking and hydrogen-bonding interactions that contribute to closer packing
      and higher density. According to the experimental results and theoretical
      analysis, the newly designed energetic salt also gives rise to a workable
      compromise in high detonation properties and desirable stabilities. These
      findings will enhance the future prospects for rational energetic materials
      design and commence a new chapter in this field. 

PMID- 25565430
TI  - Ebola outbreak in rural West Africa: epidemiology, clinical features and
      outcomes.
AB  - OBJECTIVE: To describe Ebola cases in the district Ebola management centre of in
      Kailahun, a remote rural district of Sierra Leone, in terms of geographic origin,
      patient and hospitalisation characteristics, treatment outcomes and time from
      symptom onset to admission. METHODS: Data of all Ebola cases from June 23rd to
      October 5th 2014 were reviewed. Ebola was confirmed by reverse-transcriptase
      polymerase-chain-reaction assay. RESULTS: Of 489 confirmed cases (51% male,
      median age 28 years), 166 (34%) originated outside Kailahun district. Twenty
      eight (6%) were health workers: 2 doctors, 11 nurses, 2 laboratory technicians, 7
      community health workers and 6 other cadres. More than 50% of patients had fever,
      headache, abdominal pain, diarrhoea/vomiting. An unusual feature was cough in
      40%. Unexplained bleeding was reported in 5%. Outcomes for the 489 confirmed
      cases were 227 (47%) discharges, 259 (53%) deaths and 3 transfers. Case fatality
      in health workers (68%) was higher than other occupations (52%, P = 0.05). The
      median community infectivity time was 6.5 days for both general population and
      health workers (P = 0.4). CONCLUSIONS: One in three admitted cases originated
      outside Kailahun district due to limited national access to Ebola management
      centres - complicating contact tracing, safe burial and disinfection measures.
      The comparatively high case fatality among health workers requires attention. The
      community infectivity time needs to be reduced to prevent continued transmission.

PMID- 25565432
TI  - Improving the catalytic behavior of inulin fructotransferase under high
      hydrostatic pressure.
AB  - BACKGROUND: The demand for difructose anhydride III (DFA III), a novel functional
      sweetener, is growing continuously. It is produced from inulin by inulin
      fructotransferase (IFTase). In this study, high hydrostatic pressure (HHP), as a
      clean technology, was first applied to further improve the catalytic efficiency
      of IFTase in the process. RESULTS: The maximum activity of IFTase was obtained
      under 200 MPa at 60  degrees C. Meanwhile, HHP lowered the energy barrier
      necessary for the enzymatic reaction and decreased the volume between the
      reactants and the transition state. Under this condition, the optimal pH for the
      enzymatic reaction shifted from 5.5 to 6.0. The activity was further enhanced by
      65.2% in the presence of 1.5 mol L(-1) NaCl. CONCLUSION: The catalytic reaction
      of IFTase was performed under HHP for the first time. HHP, as a promising green
      technology for bioconversion, significantly accelerated the enzymatic reaction
      under the appropriate operational conditions.

PMID- 25565433
TI  - Isolation of a hydrogen-bonded complex based on the anthranol/anthroxyl pair:
      formation of a hydrogen-atom self-exchange system.
AB  - A hydrogen-bonded complex was successfully isolated as crystals from the
      anthranol/anthroxyl pair in the self-exchange proton-coupled electron transfer
      (PCET) reaction. The anthroxyl radical was stabilized by the introduction of a 9
      anthryl group at the carbon atom at the 10-position. The hydrogen-bonded complex
      with anthranol self-assembled by pi-pi stacking to form a one-dimensional chain
      in the crystal. The conformation around the hydrogen bond was similar to that of
      the theoretically predicted PCET activated complex of the phenol/phenoxyl pair. X
      ray crystal analyses revealed the self-exchange of a hydrogen atom via the
      hydrogen bond, indicating the activation of the self-exchange PCET reaction
      between anthranol and anthroxyl. Magnetic measurements revealed that magnetic
      ordering inside the one-dimensional chain caused the inactivation of the self
      exchange reaction. 

PMID- 25565431
TI  - Previous pregnancy loss has an adverse impact on distress and behaviour in
      subsequent pregnancy.
AB  - OBJECTIVE: To investigate whether women with previous miscarriages or
      terminations have higher levels of anxiety, depression, stress, and altered
      behaviours in a subsequent pregnancy. DESIGN: A retrospective analysis of 5575
      women recruited into the Screening for Pregnancy Endpoints (SCOPE) study, a
      prospective cohort study. SETTING: Auckland, New Zealand, Adelaide, Australia,
      Cork, Ireland, and Manchester, Leeds, and London, UK. POPULATION: Healthy
      nulliparous women with singleton pregnancies. METHODS: Outcomes were recorded at
      15 and 20 weeks of gestation. MAIN OUTCOME MEASURES: Short-form State-Trait
      Anxiety Inventory (STAI) score, Perceived Stress Scale score, Edinburgh Postnatal
      Depression Scale score, and pregnancy-related behaviour measured using
      behavioural responses to pregnancy score. RESULTS: Of the 5465 women included in
      the final analysis, 559 (10%) had one and 94 (2%) had two previous miscarriages,
      and 415 (8%) had one and 66 (1%) had two previous terminations of pregnancy.
      Women with one previous miscarriage had increased anxiety (adjusted mean
      difference 1.85; 95% confidence interval, 95% CI 0.61-3.09), perceived stress
      (adjusted mean difference 0.76; 95% CI 0.48-1.03), depression (adjusted odds
      ratio, aOR 1.26; 95% CI 1.08-1.45), and limiting/resting behaviour in pregnancy
      (adjusted mean difference 0.80; 95% CI 0.62-0.97). In women with two
      miscarriages, depression was more common (aOR 1.65; 95% CI 1.01-2.70) and they
      had higher scores for limiting/resting behaviour in pregnancy (adjusted mean
      difference 1.70; 95% CI 0.90-2.53) at 15 weeks of gestation. Women with one
      previous termination displayed elevated perceived stress (adjusted mean
      difference 0.65; 95% CI 0.08-1.23) and depression (aOR 1.25; 95% 1.08-1.45) at 15
      weeks of gestation. Women with two previous terminations displayed increased
      perceived stress (adjusted mean difference 1.43; 95% CI 0.00-2.87) and depression
      (aOR 1.67; 95% 1.28-2.18). CONCLUSIONS: This study highlights the psychological
      implications of miscarriage and termination of pregnancy.

PMID- 25565434
TI  - Modeling the influence of physicochemical properties on gold nanoparticle uptake
      and elimination by Daphnia magna.
AB  - Monitoring the distribution and subsequent effects of nanoparticle contaminants
      in aquatic ecosystems will be pivotal to developing regulations that minimize
      their environmental footprint. The present study focused on the link between
      nanoparticle characteristics and Daphnia magna body burden using gold
      nanoparticles (AuNPs) with different size, shape, and surface charge
      configurations as model particles. Uptake followed first-order kinetics across
      the entire concentration range for all particles except the cationic rods, which
      demonstrated 2 distinct uptake patterns. Elimination followed the 2-compartment
      model for all particle configurations. Multiple regression analysis identified
      size and surface charge as controlling influences over AuNP uptake and
      elimination, whereas shape was regarded as inconsequential to both processes.
      Examination of the lumen-microvilli interface produced no evidence to indicate
      assimilation of the AuNPs used in the present study. Instead, these nanoparticles
      were restricted to the gut lumen and the carapace, where ingestion efficiency and
      adsorption were the primary determinants of total body burden. Models developed
      from the present data predict that D. magna will amass a higher body burden of
      larger cationic AuNPs at high concentration exposures and larger anionic AuNPs at
      low concentration exposures. A survey of the nanoparticle literature revealed
      that these trends were consistent with observations for certain nanomaterial
      exposures but could not be applied indiscriminately to all nanoparticle types and
      species.

PMID- 25565435
TI  - The aptamer-siRNA conjugates: reprogramming T cells for cancer therapy.

PMID- 25565436
TI  - New dimensions in controlling cellular function with electroceutics.

PMID- 25565438
TI  - Influence of stabilizers on the production of disulfiram-loaded poly(lactic-co
      glycolic acid) nanoparticles and their anticancer potential.
AB  - AIM: Our hypothesis was to prove that surface modifiers themselves can be used as
      stabilizers and that their entrapment efficiency is directly influenced by the
      type of stabilizers used. MATERIALS & METHODS: Particle size and the
      polydispersity index of the nanoparticles (NPs) were measured by dynamic light
      scattering, whereas the morphology of the NPs was studied by scanning electron
      microscopy. Percentage nanoparticle yield, entrapment efficiency and drug loading
      capacity were measured by ultraviolet absorbance. The physical rigidity,
      robustness and drug releasing capability of these NPs were also assessed.
      CONCLUSION: Physiochemical characterization and the 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay suggest that polysorbate 80 has the dual
      capability of being a stabilizer and a surface modifier in addition to having
      better drug entrapment properties than Pluronic(r) 188. Disulfiram, the drug that
      was loaded on these NPs, is also observed for the first time to show significant
      anticancer potential against hepatocellular carcinoma (Hep3B) cell lines.

PMID- 25565439
TI  - Effect of differential drying techniques on PLGA nanoparticles containing
      hydrophobic and hydrophilic anticancer agents.
AB  - AIM: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing both
      paclitaxel (PTX) and gemcitabine hydrochloride (GEM) were prepared and the effect
      of lyophilization and spray drying on physicochemical characteristics of these
      nanoparticles were evaluated. METHODS: Nanoemulsions were prepared by oil-in
      water emulsion solvent diffusion technique using sonication and high-pressure
      homogenization. Nanoemulsion was dried using lyophilization or spray drying and
      drug content analyzed by high-performance liquid chromatography (HPLC). RESULTS:
      The particle size of the nanoemulsion was 183.6 +/- 10.8 nm and the entrapment
      efficiency for PTX and GEM was 72.01 +/- 1.35% and 6.95 +/- 3.97%. Many
      properties including particle size, stability, surface morphology, moisture
      content, release characteristic and cellular uptake in MDCK and MDA-MB-231 cells
      were affected by the method of drying. CONCLUSION: The lyophilized nanoparticles
      were smaller in size with higher stability and cellular uptake than spray-dried
      nanoparticles.

PMID- 25565440
TI  - PLGA: a unique polymer for drug delivery.
AB  - Biodegradable polymers have played an important role in the delivery of drugs in
      a controlled and targeted manner. Polylactic-co-glycolic acid (PLGA) is one of
      the extensively researched synthetic biodegradable polymers due to its favorable
      properties. It is also known as a 'Smart Polymer' due to its stimuli sensitive
      behavior. A wide range of PLGA-based drug delivery systems have been reported for
      the treatment or diagnosis of various diseases and disorders. The present review
      provides an overview of the chemistry, physicochemical properties, biodegradation
      behavior, evaluation parameters and applications of PLGA in drug delivery.
      Different drug-polymer combinations developed into drug delivery or carrier
      systems are enumerated and discussed. 

PMID- 25565441
TI  - Solid-state protein formulations.
AB  - When formulated as liquid dosage forms, therapeutic proteins and peptides often
      show instability during handling as a result of chemical degradation. Solid
      formulations are frequently required to maintain protein stability during
      storage, transport and upon administration. Herein we highlight current
      strategies used to formulate pharmaceutical proteins in the solid form. An
      overview of the physical instabilities which can arise with proteins is first
      described. The key solidification techniques of crystallization, freeze-drying
      and particle forming technologies are then discussed. Examples of current
      commercial products that are formulated in the solid state are provided and
      include neutral protamine Hagedorn - insulin crystal suspensions, freeze-dried
      monoclonal antibodies and leuproride polylactide-co-glycolide microparticles.
      Finally, future perspectives in solid-state protein formulation are described. 

PMID- 25565442
TI  - How to overcome the limitations of current insulin administration with new non
      invasive delivery systems.
AB  - Non-invasive insulin delivery systems have potential to overcome the most
      pressing problem regarding effective treatment of diabetic patients: therapy
      compliance. To overcome this disadvantage, non-invasive routes such as oral,
      buccal, pulmonary, nasal and transdermal have been proposed. These new routes of
      insulin administration may help to suppress hypoglycemia episodes and aid to
      control weight gain and post-meal glucose. Despite all efforts the invasive route
      remains preferential, since studies on insulin administration by non-invasive
      routes conducted to date have not demonstrated clinical efficacy and safety,
      including some products introduced in the market. Therefore, the aim of this
      review is to make an update of the current state of administration of insulin by
      non-invasive routes as alternatives to the conventional invasive route. 

PMID- 25565443
TI  - Brain metastases in patients with ALK+ non-small cell lung cancer: clinical
      symptoms, treatment patterns and economic burden.
AB  - OBJECTIVE: Brain metastases (BM) are highly prevalent among anaplastic lymphoma
      kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients; yet little is
      known about their real-world treatment patterns and clinical and economic
      burdens. This study aimed to describe these patients' treatment patterns,
      symptoms, and costs. RESEARCH DESIGN AND METHODS: Retrospective study pooling
      data from three large administrative databases in the US (08/2011-06/2013). ALK+
      NSCLC patients with BM and continuous enrollment for >= 60 days before and >= 30
      days after the first observed BM diagnosis were identified by pharmacy records
      for crizotinib among patients with lung cancer and BM diagnostic codes. MAIN
      OUTCOME MEASURES: Treatment patterns, symptoms, healthcare resource utilization,
      and costs, before and after BM diagnosis. RESULTS: Of the 213 crizotinib patients
      with BM diagnoses meeting the selection criteria, 23.0% had BM prior to NSCLC
      diagnosis; 47.4% had BM prior to crizotinib initiation; 19.2% during crizotinib
      treatment; and 10.3% post-crizotinib treatment. For those diagnosed with BM after
      NSCLC diagnosis, the median time between the NSCLC and BM diagnoses was 88 days.
      Following the first observed BM diagnosis, 88.7% used chemotherapy, 63.4% had
      radiotherapy, and 31.9% had stereotactic radiosurgery. The prevalence of BM
      related symptoms substantially increased post-BM-diagnosis: fatigue (from 15% to
      39%), headaches (from 5% to 24%), and depression (from 5% to 15%). Monthly costs
      per patient averaged $5983 before the BM diagnosis and $22,645 after diagnosis.
      Patients' resource utilization increased significantly post-BM-diagnosis, with a
      3-fold increase in OP visits and a 6-fold increase in IP stays. Post-BM-diagnosis
      costs were driven by pharmacy (42.0%), inpatient (29.6%), and outpatient costs
      (26.0%). LIMITATIONS: The study sample was limited to crizotinib-treated
      patients. CONCLUSIONS: Post-BM-diagnosis, patients experience high symptom
      burden. Post-BM-diagnosis, treatment is highly variable and costly: average
      monthly costs per patient almost quadrupled post-BM-diagnosis.

PMID- 25565444
TI  - Simultaneous pancreas and kidney transplantation: current trends and future
      directions.
AB  - PURPOSE OF REVIEW: Important trends are being observed in pancreas
      transplantation in the USA. We will describe recent trends in simultaneous
      pancreas kidney (SPK) transplantation related to immunosuppression, treatment of
      rejection, and transplantation for patients of advanced age and C-peptide
      positive diabetes. RECENT FINDINGS: Rates of pancreas transplantation have
      declined, despite improved pancreatic graft outcomes. Regarding
      immunosuppression, trends in SPK transplantation include T-cell depletion
      induction therapy, waning mammalian target of rapamycin inhibitor use and steroid
      use in greater than 50% of pancreas transplant recipients with few patients
      undergoing late steroid weaning. Rejection of the pancreas may be discordant with
      the kidney after SPK and there is a greater appreciation of antibody-mediated
      rejection of the pancreas allograft. De-novo donor-specific antibody without
      graft dysfunction remains an active area of study, and the treatment for this
      condition is unclear. SPKs are being performed with greater frequency in type 2
      diabetes mellitus patients and in patients of advanced age, with exemplary
      results. SUMMARY: The current state of the art in SPK transplantation is yielding
      superb and improving results.

PMID- 25565446
TI  - Screw dislocations in complex, low symmetry oxides: core structures, energetics,
      and impact on crystal growth.
AB  - Determining the atomic structure and the influence of defects on properties of
      low symmetry oxides have long been an engineering pursuit. Here, we focus on five
      thermodynamically reversible monoclinic and orthorhombic polymorphs of dicalcium
      silicates (Ca2SiO3)-a key cement constituent-as a model system and use atomistic
      simulations to unravel the interplay between the screw dislocation core energies,
      nonplanar core structures, and Peierls stresses along different crystallographic
      planes. Among different polymorphs, we found that the alpha polymorphs (alpha
      C2S) has the largest Peierls stress, corresponding to the most brittle polymorph,
      which make it attractive for grinding processes. Interestingly, our analyses
      indicate that this polymorphs has the lowest dislocation core energy, making it
      ideal for reactivity and crystal growth. Generally, we identified the following
      order in terms of grinding efficiency based on screw dislocation analysis, alpha
      C2S > alphaH-C2S > alphaL-C2S > beta-C2S > gamma-C2S, and the following order in
      term of reactivity, alpha -C2S > alphaL-C2S > gamma-C2S > alphaH-C2S > beta-C2S.
      This information, combined with other deformation-based mechanisms, such as
      twinning and edge dislocation, can provide crucial insights and guiding
      hypotheses for experimentalists to tune the cement grinding mechanisms and
      reactivity processes for an overall optimum solution with regard to both energy
      consumption and performance. Our findings significantly broaden the spectrum of
      strategies for leveraging both crystallographic directions and crystal symmetry
      to concurrently modulate mechanics and crystal growth processes within an
      identical chemical composition. 

PMID- 25565445
TI  - Indocyanine green-loaded nanoparticles for image-guided tumor surgery.
AB  - Detecting positive tumor margins and local malignant masses during surgery is
      critical for long-term patient survival. The use of image-guided surgery for
      tumor removal, particularly with near-infrared fluorescent imaging, is a
      potential method to facilitate removing all neoplastic tissue at the surgical
      site. In this study we demonstrate a series of hyaluronic acid (HLA)-derived
      nanoparticles that entrap the near-infrared dye indocyanine green, termed
      NanoICG, for improved delivery of the dye to tumors. Self-assembly of the
      nanoparticles was driven by conjugation of one of three hydrophobic moieties:
      aminopropyl-1-pyrenebutanamide (PBA), aminopropyl-5beta-cholanamide (5betaCA), or
      octadecylamine (ODA). Nanoparticle self-assembly, dye loading, and optical
      properties were characterized. NanoICG exhibited quenched fluorescence that could
      be activated by disassembly in a mixed solvent. NanoICG was found to be nontoxic
      at physiologically relevant concentrations and exposure was not found to inhibit
      cell growth. Using an MDA-MB-231 tumor xenograft model in mice, strong
      fluorescence enhancement in tumors was observed with NanoICG using a fluorescence
      image-guided surgery system and a whole-animal imaging system. Tumor contrast
      with NanoICG was significantly higher than with ICG alone. 

PMID- 25565447
TI  - A new Agamma-globin chain variant: Hb F-Sykesville MD [Agamma113(G15)Val -> Ile;
      HBG1: c.340G>A] detected in a Caucasian baby.
AB  - The total number of hemoglobin (Hb) variants currently included in the globin
      gene server database is 1626 (November 12 2014), of which 131 are fetal Hb
      variants. These variants are observed as two different subunits of fetal Hb,
      (G)gamma- and (A)gamma-globin chains. Of the 131 documented fetal Hb variants, 73
      are (G)gamma- and 58 are (A)gamma-globin chain variants. Although they are easily
      detected at birth, as the quantity of gamma chains progressively decreases over
      the first few months of life, they are essentially undetectable after 6 months of
      age. In this report we discuss the molecular characteristics and diagnostic
      criteria of a new (A)gamma chain variant that was detected during newborn
      screening and named Hb F-Sykesville MD [(A)gamma113(G15)Val -> Ile; HBG1:
      c.340G>A].

PMID- 25565448
TI  - Optimal method for collection of umbilical cord blood: an Egyptian trial for a
      public cord blood bank.
AB  - BACKGROUND: Umbilical cord blood (UCB) contains stem cells and can be used as an
      alternative to bone marrow transplantation. Engraftment is dependent on the total
      nucleated cell (TNC) and CD34+ cell counts of the cord blood units. This study
      was designed to evaluate the effect of the method of collection of the UCB on the
      yield of the cord blood units. STUDY DESIGN AND METHODS: Informed consent was
      obtained from 100 eligible mothers for donation of cord blood. Both in utero and
      ex utero methods were used for collection. The cord blood volume was measured.
      The TNC and the CD34+ cell counts were enumerated. RESULTS: We have found that in
      utero collection gave significantly larger volumes of cord blood and higher TNC
      counts than ex utero collection. There was no significant difference between both
      methods regarding the CD34+ cell counts. This study revealed a significant
      correlation between the volume of the collected cord blood and both TNC and CD34+
      cell counts. CONCLUSION: It is better to collect cord blood in utero before
      placental delivery to optimize the quality of the cord blood unit.

PMID- 25565449
TI  - Long-term nitrogen addition causes the evolution of less-cooperative mutualists.
AB  - Human activities have altered the global nitrogen (N) cycle, and as a result,
      elevated N inputs are causing profound ecological changes in diverse ecosystems.
      The evolutionary consequences of this global change have been largely ignored
      even though elevated N inputs are predicted to cause mutualism breakdown and the
      evolution of decreased cooperation between resource mutualists. Using a long-term
      (22 years) N-addition experiment, we find that elevated N inputs have altered the
      legume-rhizobium mutualism (where rhizobial bacteria trade N in exchange for
      photosynthates from legumes), causing the evolution of less-mutualistic rhizobia.
      Plants inoculated with rhizobium strains isolated from N-fertilized treatments
      produced 17-30% less biomass and had reduced chlorophyll content compared to
      plants inoculated with strains from unfertilized control plots. Because the
      legume-rhizobium mutualism is the major contributor of naturally fixed N to
      terrestrial ecosystems, the evolution of less-cooperative rhizobia may have
      important environmental consequences. 

PMID- 25565450
TI  - Surgical delivery in under-resourced settings: building systems and capacity
      around the corner and far away.

PMID- 25565452
TI  - Article Withdrawal Statement.

PMID- 25565453
TI  - Temperature-resistant bicelles for structural studies by solid-state NMR
      spectroscopy.
AB  - Three-dimensional structure determination of membrane proteins is important to
      fully understand their biological functions. However, obtaining a high-resolution
      structure has been a major challenge mainly due to the difficulties in retaining
      the native folding and function of membrane proteins outside of the cellular
      membrane environment. These challenges are acute if the protein contains a large
      soluble domain, as it needs bulk water unlike the transmembrane domains of an
      integral membrane protein. For structural studies on such proteins either by
      nuclear magnetic resonance (NMR) spectroscopy or X-ray crystallography, bicelles
      have been demonstrated to be superior to conventional micelles, yet their
      temperature restrictions attributed to their thermal instabilities are a major
      disadvantage. Here, we report an approach to overcome this drawback through
      searching for an optimum combination of bicellar compositions. We demonstrate
      that bicelles composed of 1,2-didecanoyl-sn-glycero-3-phosphocholine (DDPC) and
      1,2-diheptanoyl-sn-glycero-3-phosphocholin (DHepPC), without utilizing additional
      stabilizing chemicals, are quite stable and are resistant to temperature
      variations. These temperature-resistant bicelles have a robust bicellar phase and
      magnetic alignment over a broad range of temperatures, between -15 and 80 
      degrees C, retain the native structure of a membrane protein, and increase the
      sensitivity of solid-state NMR experiments performed at low temperatures.
      Advantages of two-dimensional separated-local field (SLF) solid-state NMR
      experiments at a low temperature are demonstrated on magnetically aligned
      bicelles containing an electron carrier membrane protein, cytochrome b5.
      Morphological information on different DDPC-based bicellar compositions, varying
      q ratio/size, and hydration levels obtained from (31)P NMR experiments in this
      study is also beneficial for a variety of biophysical and spectroscopic
      techniques, including solution NMR and magic-angle-spinning (MAS) NMR for a wide
      range of temperatures. 

PMID- 25565451
TI  - Crystallographic and spectroscopic snapshots reveal a dehydrogenase in action.
AB  - Aldehydes are ubiquitous intermediates in metabolic pathways and their innate
      reactivity can often make them quite unstable. There are several aldehydic
      intermediates in the metabolic pathway for tryptophan degradation that can decay
      into neuroactive compounds that have been associated with numerous neurological
      diseases. An enzyme of this pathway, 2-aminomuconate-6-semialdehyde
      dehydrogenase, is responsible for 'disarming' the final aldehydic intermediate.
      Here we show the crystal structures of a bacterial analogue enzyme in five
      catalytically relevant forms: resting state, one binary and two ternary
      complexes, and a covalent, thioacyl intermediate. We also report the crystal
      structures of a tetrahedral, thiohemiacetal intermediate, a thioacyl intermediate
      and an NAD(+)-bound complex from an active site mutant. These covalent
      intermediates are characterized by single-crystal and solution-state electronic
      absorption spectroscopy. The crystal structures reveal that the substrate
      undergoes an E/Z isomerization at the enzyme active site before an sp(3)-to-sp(2)
      transition during enzyme-mediated oxidation. 

PMID- 25565454
TI  - Prediction of the structures of helical membrane proteins based on a minimum
      unfavorable contacts approach.
AB  - An understanding of structure-function relationships of membrane proteins
      continues to be a challenging problem, owing to the difficulty in obtaining their
      structures experimentally. This study suggests a method for modeling membrane
      protein structures that can be used to generate a reliable initial conformation
      prior to the use of other approaches for sampling conformations. It involves
      optimizing the orientation of hydrophilic residues so as to minimize unfavorable
      contacts with the hydrophobic tails of the lipid bilayer. Starting with the
      optimized initial conformation for three different proteins modeled based on this
      method, two independent approaches have been used for sampling the conformational
      space of the proteins. Both approaches are able to predict structures reasonably
      close to experimental structures, indicating that the initial structure enables
      the sampling of conformations that are close to the native structure. Possible
      improvements in the method for making it broadly applicable to helical membrane
      proteins are discussed.

PMID- 25565455
TI  - Dipeptidyl peptidase-4 inhibition improves cardiac function in experimental
      myocardial infarction: Role of stromal cell-derived factor-1alpha.
AB  - BACKGROUND: In addition to degrading glucagon-like peptide-1 (GLP-1), dipeptidyl
      peptidase-4 (DPP-4) inactivates several chemokines, including stromal cell
      derived factor-1alpha (SDF-1alpha), a pro-angiogenic and cardiomyocyte protective
      protein. We hypothesized that DPP-4 inhibition may confer benefit following
      myocardial infarction (MI) in the diabetic setting as a consequence of enhanced
      SDF-1alpha availability rather than potentiating GLP-1. To test this we compared
      the effects of saxagliptin with those of liraglutide and used the SDF-1alpha
      receptor (CXCR4) antagonist plerixafor. METHODS: Studies were conducted in
      streptozotocin-diabetic rats. Rats were randomized to receive saxagliptin (10
      mg/kg per day), liraglutide (0.2 mg/kg, s.c., b.i.d.), plerixafor (1 mg/kg per
      day, s.c.), saxagliptin plus plerixafor or vehicle (1% phosphate-buffered
      saline). Two weeks later, rats underwent experimental MI, with cardiac function
      examined 4 weeks after MI. RESULTS: Glycemic control and MI size were similar in
      all groups. Four weeks after MI, mortality was reduced in saxagliptin-treated
      rats compared with vehicle treatment (P < 0.05). Furthermore, rats receiving
      saxagliptin had improved cardiac function compared with vehicle-treated rats (P <
      0.05). Antagonism of CXCR4 prevented the improvement in cardiac function in
      saxagliptin-treated rats and was associated with increased mortality (P < 0.05).
      CONCLUSION: Saxagliptin-mediated DPP-4 inhibition, but not liraglutide-mediated
      GLP-1R agonism, improved cardiac function after MI independent of glucose
      lowering. These findings suggest that non-GLP-1 actions of DPP-4 inhibition, such
      as SDF-1alpha potentiation, mediate biological effects.

PMID- 25565456
TI  - A modification of Murray's law for shear-thinning rheology.
AB  - This study reformulates Murray's well-known principle of minimum work as applied
      to the cardiovascular system to include the effects of the shear-thinning
      rheology of blood. The viscous behavior is described using the extended modified
      power law (EMPL), which is a time-independent, but shear-thinning rheological
      constitutive equation. The resulting minimization problem is solved numerically
      for typical parameter ranges. The non-Newtonian analysis still predicts the
      classical cubic diameter dependence of the volume flow rate and the cubic
      branching law. The current analysis also predicts a constant wall shear stress
      throughout the vascular tree, albeit with a numerical value about 15-25% higher
      than the Newtonian analysis. Thus, experimentally observed deviations from the
      cubic branching law or the predicted constant wall shear stress in the
      vasculature cannot likely be attributed to blood's shear-thinning behavior.
      Further differences between the predictions of the non-Newtonian and the
      Newtonian analyses are highlighted, and the limitations of the Newtonian analysis
      are discussed. Finally, the range and limits of applicability of the current
      results as applied to the human arterial tree are also discussed. 

PMID- 25565458
TI  - How clinicians discuss critically ill patients' preferences and values with
      surrogates: an empirical analysis.
AB  - OBJECTIVES: Although shared decision making requires clinicians to discuss the
      patient's values and preferences, little is known about the extent to which this
      occurs with surrogates in ICUs. We sought to assess whether and how clinicians
      talk with surrogates about incapacitated patients' preferences and values.
      DESIGN: Prospective, cross-sectional study. SETTING: Five ICUs of two hospitals.
      SUBJECTS: Fifty-four physicians and 159 surrogates for 71 patients.
      INTERVENTIONS: We audio-recorded 71 conferences in which clinicians and
      surrogates discussed life-sustaining treatment decisions for an incapacitated
      patient near the end of life. Two coders independently coded each instance in
      which clinicians or surrogates discussed the patient's previously expressed
      treatment preferences or values. They subcoded for values that are commonly
      important to patients near the end of life. They also coded treatment
      recommendations by clinicians that incorporated the patient's preferences or
      values. MEASUREMENTS AND MAIN RESULTS: In 30% of conferences, there was no
      discussion about the patient's previously expressed preferences or values. In
      37%, clinicians and surrogates discussed both the patient's treatment preferences
      and values. In the remaining 33%, clinicians and surrogates discussed either the
      patient's treatment preferences or values, but not both. In more than 88% of
      conferences, there was no conversation about the patient's values regarding
      autonomy and independence, emotional well-being and relationships, physical
      function, cognitive function, or spirituality. On average, 3.8% (SD, 4.3; range,
      0-16%) of words spoken pertained to patient preferences or values. CONCLUSIONS:
      In roughly a third of ICU family conferences for patients at high risk of death,
      neither clinicians nor surrogates discussed patients' preferences or values about
      end-of-life decision making. In less than 12% of conferences did participants
      address values of high importance to most patients, such as cognitive and
      physical function. Interventions are needed to ensure patients' values and
      preferences are elicited and integrated into end-of-life decisions in ICUs.

PMID- 25565459
TI  - Stress-induced cardiomyopathy.
AB  - OBJECTIVES: Reversible stress-induced cardiac dysfunction is frequently seen as a
      complication of a multitude of acute stress states, in particular neurologic
      injuries. This dysfunction may be difficult to distinguish between that caused by
      myocardial ischemia and may impact both the treatment strategies and prognosis of
      the underlying condition. Critical care practitioners should have an
      understanding of the epidemiology, pathophysiology, clinical characteristics,
      precipitating conditions, differential diagnosis, and proposed treatments for
      stress-induced cardiomyopathy. DATA SOURCES: MEDLINE database search conducted
      from inception to August 2014, including the search terms "tako-tsubo," "stress
      induced cardiomyopathy," "neurogenic cardiomyopathy," "neurogenic stress
      cardiomyopathy," and "transient left ventricular apical ballooning syndrome". In
      addition, references from pertinent articles were used for a secondary search.
      STUDY SELECTION AND DATA EXTRACTION: After review of peer-reviewed original
      scientific articles, guidelines, and reviews resulting from the literature search
      described above, we made final selections for included references and data based
      on relevance and author consensus. DATA SYNTHESIS: Stress-induced cardiomyopathy
      occurs most commonly in postmenopausal women. It can be precipitated by emotional
      stress, neurologic injury, and numerous other stress states. Patients may present
      with symptoms indistinguishable from acute coronary syndrome or with
      electrocardiogram changes and wall motion abnormalities on echocardiogram
      following neurologic injury. Nearly all patients will have an elevated cardiac
      troponin. The underlying etiology is likely related to release of catecholamines,
      both locally in the myocardium and in the circulation. Differential diagnosis
      includes myocardial infarction, myocarditis, neurogenic pulmonary edema, and
      nonischemic cardiomyopathy. Although the natural course of stress-induced
      cardiomyopathy is resolution, treatment strategies include sympathetic blockade
      and supportive care. CONCLUSIONS: Stress-induced cardiomyopathy may mimic
      myocardial infarction and is an important condition to recognize in patients with
      underlying stress states, particularly neurologic injuries.

PMID- 25565460
TI  - Mechanical ventilation management during extracorporeal membrane oxygenation for
      acute respiratory distress syndrome: a retrospective international multicenter
      study.
AB  - OBJECTIVE: To describe mechanical ventilation settings in adult patients treated
      for an acute respiratory distress syndrome with extracorporeal membrane
      oxygenation and assess the potential impact of mechanical ventilation settings on
      ICU mortality. DESIGN: Retrospective observational study. SETTING: Three
      international high-volume extracorporeal membrane oxygenation centers. PATIENTS:
      A total of 168 patients treated with extracorporeal membrane oxygenation for
      severe acute respiratory distress syndrome from January 2007 to January 2013.
      INTERVENTIONS: We analyzed the association between mechanical ventilation
      settings (i.e. plateau pressure, tidal volume, and positive end-expiratory
      pressure) on ICU mortality using multivariable logistic regression model and Cox
      proportional hazards model. MEASUREMENT AND MAIN RESULTS: We obtained detailed
      demographic, clinical, daily mechanical ventilation settings and ICU outcome
      data. One hundred sixty-eight patients (41 +/- 14 years old; PaO2/FIO2 67 +/- 19
      mm Hg) fulfilled our inclusion criteria. Median duration of extracorporeal
      membrane oxygenation and ICU stay were 10 days (6-18 d) and 28 days (16-42 d),
      respectively. Lower positive end-expiratory pressure levels and significantly
      lower plateau pressures during extracorporeal membrane oxygenation were used in
      the French center than in both Australian centers (23.9 +/- 1.4 vs 27.6 +/- 3.7
      and 27.8 +/- 3.6; p < 0.0001). Overall ICU mortality was 29%. Lower positive end
      expiratory pressure levels (until day 7) and lower delivered tidal volume after 3
      days on extracorporeal membrane oxygenation were associated with significantly
      higher mortality (p < 0.05). In multivariate analysis, higher positive end
      expiratory pressure levels during the first 3 days of extracorporeal membrane
      oxygenation support were associated with lower mortality (odds ratio, 0.75; 95%
      CI, 0.64-0.88; p = 0.0006). Other independent predictors of ICU mortality
      included time between ICU admission and extracorporeal membrane oxygenation
      initiation, plateau pressure greater than 30 cm H2O before extracorporeal
      membrane oxygenation initiation, and lactate level on day 3 of extracorporeal
      membrane oxygenation support. CONCLUSIONS: Protective mechanical ventilation
      strategies were routinely used in high-volume extracorporeal membrane oxygenation
      centers. However, higher positive end-expiratory pressure levels during the first
      3 days on extracorporeal membrane oxygenation support were independently
      associated with improved survival. Further prospective trials on the optimal
      mechanical ventilation strategy during extracorporeal membrane oxygenation
      support are warranted.

PMID- 25565462
TI  - Postoperative radiotherapy: not all thymic malignancies are created equal.

PMID- 25565461
TI  - Noninvasive ventilation and survival in acute care settings: a comprehensive
      systematic review and metaanalysis of randomized controlled trials.
AB  - OBJECTIVE: Noninvasive ventilation is increasingly applied to prevent or treat
      acute respiratory failure, but its benefit on survival is still controversial for
      many indications. We performed a metaanalysis of randomized controlled trials
      focused on the effect of noninvasive ventilation on mortality. DATA SOURCES:
      BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical
      trials (updated December 31, 2013) were searched. STUDY SELECTION: We included
      all the randomized controlled trials published in the last 20 years performed in
      adults, reporting mortality, comparing noninvasive ventilation to any other
      treatment for prevention or treatment of acute respiratory failure or as a tool
      allowing an earlier extubation. Studies with unclear methodology, comparing two
      noninvasive ventilation modalities, or in palliative settings were excluded. DATA
      EXTRACTION: We extracted data on mortality, study design, population, clinical
      setting, comparator, and follow-up duration. DATA SYNTHESIS: Seventy-eight
      studies were analyzed. Noninvasive ventilation was associated with a reduction in
      mortality (12.6% in the noninvasive ventilation group vs 17.8% in the control
      arm; risk ratio=0.73 [0.66-0.81]; p<0.001; number needed to treat=19 with 7,365
      patients included) at the longest available follow-up. Mortality was reduced when
      noninvasive ventilation was used to treat (14.2% vs 20.6%; risk ratio=0.72;
      p<0.001; number needed to treat=16, with survival improved in pulmonary edema,
      chronic obstructive pulmonary disease exacerbation, acute respiratory failure of
      mixed etiologies, and postoperative acute respiratory failure) or to prevent
      acute respiratory failure (5.3% vs 8.3%; risk ratio=0.64 [0.46-0.90]; number
      needed to treat=34, with survival improved in postextubation ICU patients), but
      not when used to facilitate an earlier extubation. Overall results were confirmed
      for hospital mortality. Patients randomized to noninvasive ventilation maintained
      the survival benefit even in studies allowing crossover of controls to
      noninvasive ventilation as rescue treatment. CONCLUSIONS: This comprehensive
      metaanalysis suggests that noninvasive ventilation improves survival in acute
      care settings. The benefit could be lost in some subgroups of patients if
      noninvasive ventilation is applied late as a rescue treatment. Whenever
      noninvasive ventilation is indicated, an early adoption should be promoted.

PMID- 25565463
TI  - Improving pneumococcal immunization rates in an ambulatory setting.
AB  - The purpose of this quality improvement project was to improve the immunization
      rates of an at-risk adult population seen in a presurgical testing center through
      staff training and patient education. Over 24 months, there were 2257 patients
      preintervention and 2505 patients postintervention. There was a statistically
      significant difference between preintervention rate of 24% and postintervention
      rate of 47% (chi2 [1, N = 4736] = 173.8; P < .0001). Appropriate immunization of
      patients in ambulatory settings can have an important health impact.

PMID- 25565464
TI  - Enhancing the patient experience with volunteers.

PMID- 25565465
TI  - Development of a fluorescence-activated cell sorting method coupled with whole
      genome amplification to analyze minority and trace Dehalococcoides genomes in
      microbial communities.
AB  - Dehalococcoides mccartyi are functionally important bacteria that catalyze the
      reductive dechlorination of chlorinated ethenes. However, these anaerobic
      bacteria are fastidious to isolate, making downstream genomic characterization
      challenging. In order to facilitate genomic analysis, a fluorescence-activated
      cell sorting (FACS) method was developed in this study to separate D. mccartyi
      cells from a microbial community, and the DNA of the isolated cells was processed
      by whole genome amplification (WGA) and hybridized onto a D. mccartyi microarray
      for comparative genomics against four sequenced strains. First, FACS was
      successfully applied to a D. mccartyi isolate as positive control, and then
      microarray results verified that WGA from 10(6) cells or ~1 ng of genomic DNA
      yielded high-quality coverage detecting nearly all genes across the genome. As
      expected, some inter- and intrasample variability in WGA was observed, but these
      biases were minimized by performing multiple parallel amplifications. Subsequent
      application of the FACS and WGA protocols to two enrichment cultures containing
      ~10% and ~1% D. mccartyi cells successfully enabled genomic analysis. As proof of
      concept, this study demonstrates that coupling FACS with WGA and microarrays is a
      promising tool to expedite genomic characterization of target strains in
      environmental communities where the relative concentrations are low.

PMID- 25565466
TI  - Highly diastereoselective palladium-catalyzed indium-mediated allylation of
      chiral hydrazones.
AB  - The general and efficient palladium-catalyzed indium-mediated allylation of
      chiral hydrazones was accomplished with excellent yield (72-92%) and
      diastereoselectivity (up to 99:1). The development of this reaction and the
      substrate scope are described. The conversion was found to be proportional to the
      phosphine concentration, which provided insight into the mechanism and competing
      pathways of the redox transmetalation process. 

PMID- 25565467
TI  - Phase steps and resonator detuning measurements in microresonator frequency
      combs.
AB  - Experiments and theoretical modelling yielded significant progress toward
      understanding of Kerr-effect induced optical frequency comb generation in
      microresonators. However, the simultaneous Kerr-mediated interaction of hundreds
      or thousands of optical comb frequencies with the same number of resonator modes
      leads to complicated nonlinear dynamics that are far from fully understood. An
      important prerequisite for modelling the comb formation process is the knowledge
      of phase and amplitude of the comb modes as well as the detuning from their
      respective microresonator modes. Here, we present comprehensive measurements that
      fully characterize optical microcomb states. We introduce a way of measuring
      resonator dispersion and detuning of comb modes in a hot resonator while
      generating an optical frequency comb. The presented phase measurements show
      unpredicted comb states with discrete pi and pi/2 steps in the comb phases that
      are not observed in conventional optical frequency combs. 

PMID- 25565468
TI  - Author response to 'Staphylococcus aureus and primary lysis of eosinophils' by Dr
      Persson.

PMID- 25565457
TI  - Chest compression rates and survival following out-of-hospital cardiac arrest.
AB  - OBJECTIVE: Guidelines for cardiopulmonary resuscitation recommend a chest
      compression rate of at least 100 compressions/min. A recent clinical study
      reported optimal return of spontaneous circulation with rates between 100 and
      120/min during cardiopulmonary resuscitation for out-of-hospital cardiac arrest.
      However, the relationship between compression rate and survival is still
      undetermined. DESIGN: Prospective, observational study. SETTING: Data is from the
      Resuscitation Outcomes Consortium Prehospital Resuscitation IMpedance threshold
      device and Early versus Delayed analysis clinical trial. PARTICIPANTS: Adults
      with out-of-hospital cardiac arrest treated by emergency medical service
      providers. INTERVENTIONS: None. MEASUREMENTS MAIN RESULTS: Data were abstracted
      from monitor-defibrillator recordings for the first five minutes of emergency
      medical service cardiopulmonary resuscitation. Multiple logistic regression
      assessed odds ratio for survival by compression rate categories (<80, 80-99, 100
      119, 120-139, >=140), both unadjusted and adjusted for sex, age, witnessed
      status, attempted bystander cardiopulmonary resuscitation, location of arrest,
      chest compression fraction and depth, first rhythm, and study site. Compression
      rate data were available for 10,371 patients; 6,399 also had chest compression
      fraction and depth data. Age (mean+/-SD) was 67+/-16 years. Chest compression
      rate was 111+/-19 per minute, compression fraction was 0.70+/-0.17, and
      compression depth was 42+/-12 mm. Circulation was restored in 34%; 9% survived to
      hospital discharge. After adjustment for covariates without chest compression
      depth and fraction (n=10,371), a global test found no significant relationship
      between compression rate and survival (p=0.19). However, after adjustment for
      covariates including chest compression depth and fraction (n=6,399), the global
      test found a significant relationship between compression rate and survival
      (p=0.02), with the reference group (100-119 compressions/min) having the greatest
      likelihood for survival. CONCLUSIONS: After adjustment for chest compression
      fraction and depth, compression rates between 100 and 120 per minute were
      associated with greatest survival to hospital discharge.

PMID- 25565469
TI  - mental health care for people who identify as lesbian, gay, bisexual,
      transgender, and (or) queer.

PMID- 25565471
TI  - Nonsuicidal self-injury: what we know, and what we need to know.

PMID- 25565472
TI  - Expanding and clarifying the role of emotion regulation in nonsuicidal self
      injury.
AB  - OBJECTIVE: Deficits in emotion regulation have been implicated in nonsuicidal
      self-injury (NSSI) by both theory and research. Research indicates that NSSI is
      commonly performed as an emotion regulation strategy, as it often decreases the
      experience of negative affect. People who engage in NSSI often report greater
      emotion dysregulation than those without an NSSI history. Further, interventions
      that have demonstrated effectiveness in reducing NSSI involve a focus on emotion
      regulation skills. Given the important role of emotion regulation in NSSI,
      research should continue to develop our understanding of this construct. METHODS:
      We conducted a review of relevant research in emotion regulation and
      dysregulation and specific emotion regulation strategies in NSSI. RESULTS: First,
      we provide an overview of current research on emotion regulation and
      dysregulation in NSSI. Second, we discuss the application of a specific emotion
      regulation model to NSSI research, and review research on NSSI supporting the use
      of this model. CONCLUSION: NSSI has been associated with an emotion regulation
      function and trait emotion dysregulation among people who self-injure. Relevant
      research provides initial support for the applicability of a specific model of
      emotion regulation to NSSI. We suggest directions for future research to continue
      to cultivate our understanding of emotion regulation in NSSI.

PMID- 25565474
TI  - Research experience in psychiatry residency programs across Canada: current
      status.
AB  - OBJECTIVE: To determine the current status of research experience in psychiatry
      residency programs across Canada. METHOD: Coordinators of Psychiatric Education
      (COPE) resident representatives from all 17 psychiatry residency programs in
      Canada were asked to complete a survey regarding research training requirements
      in their programs. RESULTS: Among the 17 COPE representatives, 15 completed the
      survey, representing 88% of the Canadian medical schools that have a psychiatry
      residency program. Among the 15 programs, 11 (73%) require residents to conduct a
      scholarly activity to complete residency. Some of these programs incorporated
      such a requirement in the past 5 years. Ten respondents (67%) reported
      availability of official policy and (or) guidelines on resident research
      requirements. Among the 11 programs that have a research requirement, 10 (91%)
      require residents to complete 1 scholarly activity; 1 requires completion of 2
      scholarly activities. Eight (53%) residency programs reported having a separate
      research track. All of the programs have a research coordinator and 14 (93%)
      programs provide protected time to residents for conducting research. The 3 most
      common types of scholarly activities that qualify for the mandatory research
      requirement are a full independent project (10 programs), a quality improvement
      project (8 programs), and assisting in a faculty project (8 programs). Six
      programs expect their residents to present their final work in a departmental
      forum. None of the residency programs require publication of residents' final
      work. CONCLUSIONS: The current status of the research experience during
      psychiatry residency in Canada is encouraging but there is heterogeneity across
      the programs.

PMID- 25565475
TI  - Changing perceptions of mental health in Canada.
AB  - OBJECTIVE: Epidemiologic studies typically assess mental health using diagnostic
      measures or symptom severity measures. However, perceptions are also important.
      The objective of our study was to evaluate trends in perceived mental health in
      Canada during the past 20 years using data collected in a series of surveys.
      METHOD: Perceived mental health status, the stressfulness of most days, and
      perceived general health, have been repeatedly measured in national surveys. In
      our study, the resulting frequencies and 95% confidence intervals were
      calculated. Distress was also assessed in the same surveys with the Kessler 6
      Psychological Distress Scale, and analyzed using mean scores and frequencies
      based on cut-points. Data synthesis used forest plots. Time trends were assessed
      using random effects meta-regression models. RESULTS: No detectable changes in
      distress were found. Similarly, self-rated general health remained stable.
      However, over time, Canadians became slightly more likely to report that their
      mental health was merely fair or poor. Conversely, they have been progressively
      less likely to perceive that their lives are quite a bit or extremely stressful.
      CONCLUSION: While these observations are ecological, the 2 trends may be related:
      distressing emotional experiences may increasingly be interpreted as evidence of
      a disturbance of mental health rather than a reaction to stressful circumstances.
      These changing perceptions should not be misinterpreted as an epidemic of poor
      mental health.

PMID- 25565473
TI  - Treating nonsuicidal self-injury: a systematic review of psychological and
      pharmacological interventions.
AB  - OBJECTIVE: Nonsuicidal self-injury (NSSI), the deliberate, self-inflicted damage
      of bodily tissue without the intent to die, is associated with various negative
      outcomes. Although basic and epidemiologic research on NSSI has increased during
      the last 2 decades, literature on effective interventions targeting NSSI is still
      emerging. Here, we present a comprehensive, systematic review of existing
      psychological and pharmacological treatments designed specifically for NSSI, or
      including outcome assessments examining change in NSSI. METHOD: We conducted a
      systematic search of PsycINFO, MEDLINE, and ERIC databases to retrieve relevant
      articles that met inclusion criteria; specifically, uncontrolled and controlled
      trials that 1) presented quantitative outcome data on NSSI, and 2) clearly
      differentiated NSSI from suicidal self-injury (SSI). Consistent with the
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, definition
      of NSSI, we excluded studies examining populations with developmental or
      intellectual disabilities, or with psychotic disorders. RESULTS: Several
      interventions appear to hold promise for reducing NSSI, including dialectical
      behaviour therapy, emotion regulation group therapy, manual-assisted cognitive
      therapy, dynamic deconstructive psychotherapy, atypical antipsychotics
      (aripiprazole), naltrexone, and selective serotonin reuptake inhibitors (with or
      without cognitive-behavioural therapy). Nevertheless, there remains a paucity of
      well-controlled studies investigating treatment efficacy for NSSI. CONCLUSIONS:
      Structured psychotherapeutic approaches focusing on collaborative therapeutic
      relationships, motivation for change, and directly addressing NSSI behaviours
      seem to be most effective in reducing NSSI. Medications targeting the
      serotonergic, dopaminergic and opioid systems also have demonstrated some
      benefits. Future studies employing controlled designs as well as a clear
      delineation of NSSI and SSI will improve knowledge regarding treatment effects.

PMID- 25565476
TI  - Treatment patterns, resource use, and economic outcomes associated with atypical
      antipsychotic prescriptions in children and adolescents with attention-deficit
      hyperactivity disorder in quebec.
AB  - OBJECTIVE: To assess treatment patterns, health care resource utilization (HRU),
      and costs among previously stimulant-treated children and adolescents with
      attention-deficit hyperactivity disorder (ADHD) receiving atypical antipsychotic
      (AAP) prescriptions in Quebec. METHODS: Health care claims data extracted from
      Quebec's provincial health plan database between March 2007 and February 2012
      were analyzed. Children and adolescents (6 to 17 years) with ADHD who were taking
      a stimulant and either switched to, or augmented with, an AAP (with the first AAP
      defined as the index AAP) without a documented diagnosis for which AAPs are
      Health Canada-approved were included. Discontinuation, augmentation, and
      switching of the index AAP during the 12-month, follow-up period were estimated
      using Kaplan-Meier survival analysis. HRU and costs for the 6 months before
      (baseline period) and after initiation of the index AAP were compared. RESULTS: A
      total of 453 children and adolescents with ADHD, mostly male (74.6%) and aged 6
      to 12 years (73.7%), met the inclusion criteria. The 12-month discontinuation,
      augmentation, and switching rates were 45.5%, 68.2%, and 80.7%, respectively.
      Patients had, on average, more all-cause prescription fills (22.2, compared with
      13.3) and incurred more all-cause pharmacy ($889, compared with $710), total
      medical ($1096, compared with $644), and total health care ($1985, compared with
      $1354) costs during the 6-month study period than during the 6-month baseline
      period (all P < 0.05). Similarly, ADHD-related total health care costs were
      higher during the study period ($1269, compared with $835; P < 0.05); all-cause
      and ADHD-related total health care costs increased by 46.6% and 52.0%,
      respectively. CONCLUSION: Use of an AAP among stimulant-treated children and
      adolescents with ADHD in Quebec was associated with high rates of therapy changes
      and increased HRU and costs.

PMID- 25565477
TI  - Antidepressant use in Canada has stopped increasing.
AB  - OBJECTIVE: Large increases in the use of antidepressants (ADs) were reported in
      the past 2 decades in many countries, including Canada. Our objective was to
      determine whether this pattern of increasing use has continued, using data from a
      2012 national mental health survey. METHOD: During the past 2 decades, a series
      of Canadian national health surveys have evaluated AD use in the household
      population. Some of these surveys have assessed past 2-day use whereas others
      have assessed self-reported past-month use. We applied meta-regression methods as
      a methodological strategy to address this heterogeneity and to examine long-term
      trends, incorporating 2012 data. RESULTS: In keeping with prior reports, AD use
      rapidly increased in the 1990s and early 2000s. However, the 2012 data suggest
      that these increases have slowed or perhaps even stopped in recent years. A post
      hoc examination of longitudinal data from the National Population Health Survey
      reinforced the impression of a levelling off in the use of these medications.
      CONCLUSION: The frequency of AD use may now be stabilizing in the Canadian
      population. This emerging steady state may reflect a contemporary balance between
      the perceived need, perceived effectiveness, and acceptability of these
      medications in the general population.

PMID- 25565479
TI  - Partial hospitalization treatment of the alexithymic patient: a case study.
AB  - Patients with alexithymia are a challenge to engage in treatment and require a
      diverse range of interventions to realize benefit. A partial hospitalization
      treatment program, offering multiple forms of group therapy in an integrated
      system, may be particularly helpful for patients with alexithymia. We examine the
      course of treatment for one alexithymic patient who participated in an 18-week
      intensive group- and dynamically oriented treatment program in Edmonton. Group
      support and feedback emerged as important elements in the treatment approach.
      Other features of the approach overlap with treatment guidelines for alexithymia
      found in the literature. 

PMID- 25565478
TI  - Mucosal immunization with PsaA protein, using chitosan as a delivery system,
      increases protection against acute otitis media and invasive infection by
      Streptococcus pneumoniae.
AB  - As infection with Streptococcus pneumoniae (mainly via the mucosal route) is a
      leading cause of acute otitis media, sinus and bacterial pneumonia, the mucosal
      immunity plays an important role in the prevention of pneumococcal diseases.
      Therefore, intranasal vaccination may be an effective immunization strategy, but
      requires appropriate mucosal vaccine delivery systems. In this work, chitosan was
      used as a mucosal delivery system to form chitosan-PsaA nanoparticles based on
      ionotropic gelation methods and used to immunize BALB/c mice intranasally.
      Compared to mice immunized with naked PsaA, levels of IFN-gamma, IL-17A and IL-4
      in spleen lymphocytes, the systemic (IgG in serum) and mucosal (IgA in mucosal
      lavage) specific antibodies were enhanced significantly in mice inoculated with
      chitosan-PsaA. Furthermore, increased protection against acute otitis media
      following middle ear challenge with pneumococcus serotype 14, and improved
      survival following intraperitoneal challenge with pneumococcus serotype 3 or
      serotype 14, was found in the mice immunized with chitosan-PsaA nanoparticles.
      Thus, intranasal immunization with chitosan-PsaA can successfully induce mucosal
      and systemic immune responses and increase protection against pneumococcal acute
      otitis media and invasive infections. Hence, intranasal immunization with PsaA
      protein, based on chitosan as a delivery system, is an efficient immunization
      strategy for preventing pneumococcal infections. 

PMID- 25565480
TI  - Cognitive rehabilitation with right hemifield eye-patching for patients with sub
      acute stroke and visuo-spatial neglect: a randomized controlled trial.
AB  - OBJECTIVE: To assess whether, following a right-hemisphere stroke, the combined
      administration of computer-based cognitive rehabilitation and right hemifield eye
      patching in patients with visuo-spatial neglect is more effective than computer
      based cognitive rehabilitation alone. METHODS: Twelve patients were randomized
      into two treatment groups: a single treatment group (n = 7) and a combination
      treatment group (n = 5). In both cases, the treatment consisted of a mean number
      of 15 sessions, each lasting 1 hour. Visuo-spatial neglect was assessed using a
      specific exploration protocol (Bell Cancellation Test, Figure Copying of Odgen,
      Line Bisection, Baking Tray Task and Reading Task). The functional effects of the
      treatment were assessed using the Catherine Bergego Scale. RESULTS: Significant
      between-group differences were observed when comparing the pre- and post
      treatment scores for the Reading Task. No differences were observed in either
      group in the Catherine Bergego Scale administered at baseline and at the final
      intervention. CONCLUSION: The results obtained do not allow one to conclude that
      the combination treatment with cognitive rehabilitation and right hemifield eye
      patching is more effective than cognitive rehabilitation alone. Although partial
      improvement in the performance of neuropsychological tests was observed, this
      improvement is not present at functional level.

PMID- 25565481
TI  - The Potential Utility of the Patient Health Questionnaire as a Screener for
      Psychiatric Comorbidity in a Chronic Disabling Occupational Musculoskeletal
      Disorder Population.
AB  - OBJECTIVES: The patient health questionnaire (PHQ) is designed for screening
      psychopathology in primary care settings. However, little is known about its
      clinical utility in other chronic pain populations, which usually have high
      psychiatric comorbidities. DESIGN: A consecutive cohort of 546 patients with
      chronic disabling occupational musculoskeletal disorder (CDOMD) was administered
      and compared upon psychosocial assessments, including the PHQ and a structured
      clinical interview for DSM-IV (SCID). Four PHQ modules were assessed: major
      depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder
      (PD), and alcohol use disorders (AUD) [including both alcohol abuse and
      dependence]. Based on the SCID diagnosis, sensitivity and specificity were
      determined. RESULTS: The specificity of the PHQ ranged from moderate to high for
      all 4 PHQ modules (MDD, 0.79; GAD, 0.67; PD, 0.89; AUD, 0.97). However, the
      sensitivity was relatively low: MDD (0.58); GAD (0.61); PD (0.49); and AUD
      (0.24). The PHQ was also associated with psychosocial variables. Patients whose
      PHQ showed MDD, GAD, or PD reported significantly more depressive symptoms and
      perceived disability than patients who did not (Ps < 0.001). Patients with MDD or
      GAD reported significantly higher pain than those without (Ps < 0.001).
      CONCLUSIONS: The strong specificity of the PHQ appears to be its primary strength
      for this cohort. Due to its high specificity, the PHQ could be employed as an
      additional screening tool to help rule out potential psychiatric comorbidity in
      patients with CDOMD. The low sensitivity of the PHQ in this population, however,
      remains a weakness of the PHQ.

PMID- 25565482
TI  - Mediation of effects of a theory-based behavioral intervention on self-reported
      physical activity in South African men.
AB  - OBJECTIVE: Increasing physical activity is an important public-health goal
      worldwide, but there are few published mediation analyses of physical-activity
      interventions in low-to-middle-income countries like South Africa undergoing a
      health transition involving markedly increased mortality from non-communicable
      diseases. This article reports secondary analyses on the mediation of a theory-of
      planned-behavior-based behavioral intervention that increased self-reported
      physical activity in a trial with 1181 men in Eastern Cape Province, South
      Africa. METHOD: Twenty-two matched-pairs of neighborhoods were randomly selected.
      Within pairs, neighborhoods were randomized to a health-promotion intervention or
      an attention-matched control intervention with baseline, immediate-post, and 6-
      and 12-month post-intervention assessments. Theory-of-planned-behavior constructs
      measured immediately post-intervention were tested as potential mediators of the
      primary outcome, self-reported physical activity averaged over the 6- and 12
      month post-intervention assessments, using a product-of-coefficients approach in
      a generalized-estimating-equations framework. Data were collected in 2007-2010.
      RESULTS: Attitude, subjective norm, self-efficacy, and intention were significant
      mediators of intervention-induced increases in self-reported physical activity.
      The descriptive norm, not affected by the intervention, was not a mediator, but
      predicted increased self-reported physical activity. CONCLUSION: The results
      suggest that interventions targeting theory-of-planned-behavior constructs may
      contribute to efforts to increase physical activity to reduce the burden of non
      communicable diseases among South African men.

PMID- 25565484
TI  - Quadratic Associations Between Empathy and Depression as Moderated by Emotion
      Dysregulation.
AB  - Empathic tendencies have been associated with interpersonal and psychological
      benefits, but empathy at extreme levels or in combination with certain personal
      characteristics may contribute to risk for depression. This study tested the
      moderating role of cognitive emotion regulation in depression's association with
      empathy using nonlinear models. Young adults (N = 304; 77% female; M = 19 years)
      completed measures of cognitive emotion regulation strategies, depression, and
      affective and cognitive empathy. Individuals with good regulation had low levels
      of depression overall and their depression symptoms were lowest when levels of
      affective empathy were average. Individuals with poor regulation had high levels
      of depression overall, particularly when levels of empathy were moderate to high.
      Extremely high and low levels of cognitive empathy were associated with elevated
      depression, and this association was not moderated by regulation. These findings
      suggest tendencies to respond empathically to others' needs is neither an
      adaptive nor maladaptive characteristic but rather moderate empathy, particularly
      in the context of good regulation, may offer the greatest protection against
      depression.

PMID- 25565483
TI  - Prevalence of colonoscopy before age 50.
AB  - OBJECTIVE: Describe the prevalence of colonoscopy before age 50, when guidelines
      recommend initiation of colorectal cancer screening for average risk individuals.
      METHOD: We assembled administrative health records that captured receipt of
      colonoscopy between 40 and 49-years of age for a cohort of 204,758 50-year-old
      members of four US health plans and used backward recurrence time models to
      estimate trends in receipt of colonoscopy before age 50 and variation in early
      colonoscopy by age and sex. We also used self-reported receipt of colonoscopy
      from 27,157 40- to 49-year-old respondents to the 2010 National Health Interview
      Survey (NHIS) to estimate the association between early colonoscopy and sex,
      race/ethnicity, and geographic location based on logistic regression models that
      accounted for the complex NHIS sampling design. RESULTS: About 5% of the health
      plan cohort had a record of colonoscopy before age 50. Receipt of early
      colonoscopy increased significantly from 1999 to 2010 (test for linear trend,
      p<0.0001), was more likely among women than men (RR=1.9, 95% CI 1.14-1.24) and in
      the east coast health plan compared to west coast and Hawaii plans. The NHIS
      analysis found that early colonoscopy was more likely in Northeastern residents
      compared to residents in the West (odds ratio=1.75, 95% CI 1.28-2.39).
      CONCLUSION: Colonoscopy before age 50 is increasingly common.

PMID- 25565485
TI  - The effects of long-chain omega-3 fish oils and multivitamins on cognitive and
      cardiovascular function: a randomized, controlled clinical trial.
AB  - OBJECTIVE: Fish oils and multivitamins are two of the most commonly used dietary
      supplements. Fish oil use may reduce vascular risk factors associated with
      cognitive decline, thus providing benefits to both heart and brain health.
      Multivitamins may also have direct effects on brain function. The present study
      investigated the effects of fish oil, with and without the addition of a
      multivitamin, on cognitive and cardiovascular function. METHODS: In a randomized,
      placebo-controlled, double-blind fashion, 160 healthy adults aged 50-70 years
      were randomized to receive either 3 g of fish oil (240 mg eicosapentaenoic acid
      [EPA] + 240 mg docosahexaenoic acid [DHA]) with a multivitamin, 6 g of fish oil
      (480 mg EPA + 480 mg DHA) with a multivitamin, or 6 g of fish oil without a
      multivitamin or a placebo. Cognitive performance, brachial blood pressure, and
      aortic (central) blood pressure were measured at baseline, 6 weeks, and 16 weeks.
      RESULTS: Treatment allocation had no effect on the primary cognitive outcomes at
      endpoint. Absolute increases in the red blood cell omega-3/6 ratio were
      associated with improvements in spatial working memory. The group receiving 6 g
      fish oil without the multivitamin displayed a significant decrease in aortic
      pulse pressure and aortic augmentation pressure, two measures of aortic blood
      pressure and aortic stiffness. CONCLUSIONS: Fish oil decreased aortic pulse
      pressure and augmentation pressure. Reductions in aortic blood pressure were not
      accompanied by consistent improvements in cognition.

PMID- 25565486
TI  - Down-regulated SOX4 expression suppresses cell proliferation, metastasis and
      induces apoptosis in Xuanwei female lung cancer patients.
AB  - The transcription factor SOX4 has functional importance in foetal lung maturation
      and tumorigenesis in a number of cancers. However, its biological functions in
      the progression of lung tumorigenesis remain unclear. In this study, we found
      that the expression levels of SOX4 mRNA and protein were significantly higher in
      Xuanwei female lung cancer tissues than in benign lung lesions. The patients with
      high expression of the SOX4 protein had a higher pathological grade, lymph node
      (LN) metastasis, poor tumor differentiation and worse prognosis than those
      patients with low expression of SOX4. Knockdown of the SOX4 gene in the Xuanwei
      female lung cancer cell line XWLC-05 resulted in apoptotic morphological changes,
      decreased cell proliferation, invasion and migration. Furthermore, knockdown of
      the SOX4 gene resulted in obvious sub-G1 peaks and induction of apoptosis through
      upregulation of caspase-3 expression, while in cells treated with a caspase-3
      inhibitor, apoptosis induced by silencing SOX4 expression was inhibited. In vivo
      analysis in nude mice further confirmed that knockdown of SOX4 suppressed tumor
      growth. In conclusion, SOX4 appears to be an important tumor suppressor gene in
      the regulation of Xuanwei female lung cancer cell proliferation, apoptosis and
      metastases, and it may be a potential target for effective lung cancer therapy.

PMID- 25565487
TI  - Risk factors and screening instruments to predict adverse outcomes for
      undifferentiated older emergency department patients: a systematic review and
      meta-analysis.
AB  - OBJECTIVES: A significant proportion of geriatric patients experience suboptimal
      outcomes following episodes of emergency department (ED) care. Risk
      stratification screening instruments exist to distinguish vulnerable subsets, but
      their prognostic accuracy varies. This systematic review quantifies the
      prognostic accuracy of individual risk factors and ED-validated screening
      instruments to distinguish patients more or less likely to experience short-term
      adverse outcomes like unanticipated ED returns, hospital readmissions, functional
      decline, or death. METHODS: A medical librarian and two emergency physicians
      conducted a medical literature search of PubMed, EMBASE, SCOPUS, CENTRAL, and
      ClinicalTrials.gov using numerous combinations of search terms, including
      emergency medical services, risk stratification, geriatric, and multiple related
      MeSH terms in hundreds of combinations. Two authors hand-searched relevant
      specialty society research abstracts. Two physicians independently reviewed all
      abstracts and used the revised Quality Assessment of Diagnostic Accuracy Studies
      instrument to assess individual study quality. When two or more qualitatively
      similar studies were identified, meta-analysis was conducted using Meta-DiSc
      software. Primary outcomes were sensitivity, specificity, positive likelihood
      ratio (LR+), and negative likelihood ratio (LR-) for predictors of adverse
      outcomes at 1 to 12 months after the ED encounters. A hypothetical test-treatment
      threshold analysis was constructed based on the meta-analytic summary estimate of
      prognostic accuracy for one outcome. RESULTS: A total of 7,940 unique citations
      were identified yielding 34 studies for inclusion in this systematic review.
      Studies were significantly heterogeneous in terms of country, outcomes assessed,
      and the timing of post-ED outcome assessments. All studies occurred in ED
      settings and none used published clinical decision rule derivation methodology.
      Individual risk factors assessed included dementia, delirium, age, dependency,
      malnutrition, pressure sore risk, and self-rated health. None of these risk
      factors significantly increased the risk of adverse outcome (LR+ range = 0.78 to
      2.84). The absence of dependency reduces the risk of 1-year mortality (LR- =
      0.27) and nursing home placement (LR- = 0.27). Five constructs of frailty were
      evaluated, but none increased or decreased the risk of adverse outcome. Three
      instruments were evaluated in the meta-analysis: Identification of Seniors at
      Risk, Triage Risk Screening Tool, and Variables Indicative of Placement Risk.
      None of these instruments significantly increased (LR+ range for various outcomes
      = 0.98 to 1.40) or decreased (LR- range = 0.53 to 1.11) the risk of adverse
      outcomes. The test threshold for 3-month functional decline based on the most
      accurate instrument was 42%, and the treatment threshold was 61%. CONCLUSIONS:
      Risk stratification of geriatric adults following ED care is limited by the lack
      of pragmatic, accurate, and reliable instruments. Although absence of dependency
      reduces the risk of 1-year mortality, no individual risk factor, frailty
      construct, or risk assessment instrument accurately predicts risk of adverse
      outcomes in older ED patients. Existing instruments designed to risk stratify
      older ED patients do not accurately distinguish high- or low-risk subsets.
      Clinicians, educators, and policy-makers should not use these instruments as
      valid predictors of post-ED adverse outcomes. Future research to derive and
      validate feasible ED instruments to distinguish vulnerable elders should employ
      published decision instrument methods and examine the contributions of
      alternative variables, such as health literacy and dementia, which often remain
      clinically occult.

PMID- 25565488
TI  - The effect of laboratory testing on emergency department length of stay: a
      multihospital longitudinal study applying a cross-classified random-effect
      modeling approach.
AB  - OBJECTIVES: The objective was to examine the relationship between laboratory
      testing (including test volume and turnaround time [TAT]) and emergency
      department (ED) length of stay (LOS), using linked patient-level data from four
      hospitals across 4 years. METHODS: This was a retrospective, multisite cohort
      study of patients presenting to any one of four EDs in New South Wales,
      Australia, during a 2-month period (August and September) in 2008, 2009, 2010,
      and 2011. Data from ED information systems were linked to laboratory test data. A
      cross-classified random-effect modeling approach was applied to identify factors
      affecting ED LOS, taking into account the correlation between patients'
      presentations at the same hospital and/or in the same calendar year. Number of
      test order episodes (tests ordered at one point in time during the ED stay) and
      TAT (time from laboratory order receipt to result available) were examined.
      RESULTS: As the number of test order episodes increased, so did the duration of
      patient ED LOS (p < 0.0001). For every five additional tests ordered per test
      order episode, the median ED LOS increased by 10 minutes (2.9%, p < 0.0001); each
      30-minute increase in TAT was, on average, associated with a 5.1% (17 minutes; p
      < 0.0001) increase in ED LOS, after adjustment for other factors. Patients
      presenting to the ED at night (7 p.m. to 7 a.m.) had longer stays than those
      presenting during the daytime, although the median TATs at nights were shorter
      than those during the daytime. CONCLUSIONS: Laboratory testing has a direct
      effect on patients' LOS in ED. Laboratory TAT, number of testing episodes, and
      test volume influence ED LOS. Targeted increases of ED resources and staffing
      after-hours may also contribute to reductions in ED LOS.

PMID- 25565489
TI  - Identification of acute stroke using quantified brain electrical activity.
AB  - OBJECTIVES: Acute stroke is a leading cause of brain injury and death and
      requires rapid and accurate diagnosis. Noncontrast head computed tomography (CT)
      is the first line for diagnosis in the emergency department (ED). Complicating
      rapid triage are presenting conditions that clinically mimic stroke. There is an
      extensive literature reporting clinical utility of brain electrical activity in
      early diagnosis and management of acute stroke. However, existing technologies do
      not lend themselves to easily acquired rapid evaluation. This investigation used
      an independently derived classifier algorithm for the identification of traumatic
      structural brain injury based on brain electrical activity recorded from a
      reduced frontal montage to explore the potential clinical utility of such an
      approach in acute stroke assessment. METHODS: Adult patients (age 18 to 95 years)
      presenting with stroke-like and/or altered mental status symptoms were recruited
      from urban academic EDs as part of a large research study evaluating the clinical
      utility of quantitative brain electrical activity in acutely brain-injured
      patients. All patients from the parent study who had confirmed strokes, and a
      control group of stroke mimics (those with final ED diagnoses of migraine or
      syncope), were selected for this study. All stroke patients underwent head CT
      scans. Some patients with negative CTs had further imaging with magnetic
      resonance imaging (MRI). Ten minutes of electroencephalographic data were
      acquired on a hand-held device in development, from five frontal electrodes. Data
      analyses were done offline. A Structural Brain Injury Index (SBII) was derived
      using an independently developed binary discriminant classification algorithm
      whose input was specified features of brain electrical activity. The SBII was
      previously found to have high accuracy in the identification of traumatic brain
      injured patients who were found to have brain injury on CT (CT+). This algorithm
      was applied to patients in this study and used to classify patients as CT+ or not
      CT+. Performance was assessed using sensitivity, specificity, and negative and
      positive predictive values (NPV, PPV). RESULTS: Forty-eight stroke patients (31
      ischemic and 17 hemorrhagic) and 135 stroke mimic controls were included. Within
      the ischemic population, approximately half were CT- but later confirmed for
      stroke with MRI (CT-/MRI+). Sensitivity to stroke was 91.7%, specificity 50.4%
      (to stroke mimic), NPV 94.4%, and PPV 39.6%. Eighty percent of the CT-/MRI+
      ischemic strokes were correctly identified at the time of the CT- scan.
      CONCLUSIONS: Despite a small population and the use of a classifier without the
      benefit of training on a stroke population, these data suggest that a rapidly
      acquired, easy-to-use system to assess brain electrical activity at the time of
      evaluation of acute stroke could be a valuable adjunct to current clinical
      practice.

PMID- 25565490
TI  - R & P: the medical education scarlet letters.

PMID- 25565491
TI  - What does remediation and probation status mean? A survey of emergency medicine
      residency program directors.
AB  - OBJECTIVES: Emergency medicine (EM) residency program directors (PDs) nationwide
      place residents on remediation and probation. However, the Accreditation Council
      for Graduate Medical Education and the EM PDs have not defined these terms, and
      individual institutions must set guidelines defining a change in resident status
      from good standing to remediation or probation. The primary objective of this
      study was to determine if EM PDs follow a common process to guide actions when
      residents are placed on remediation and probation. METHODS: An anonymous
      electronic survey was distributed to EM PDs via e-mail using SurveyMonkey to
      determine the current practice followed after residents are placed on remediation
      or probation. The survey queried four designations: informal remediation, formal
      remediation, informal probation, and formal probation. These designations were
      compared for deficits in the domains of medical knowledge (MK) and non-MK
      remediation. The survey asked what process for designation exists and what
      actions are triggered, specifically if documentation is placed in a resident's
      file, if the graduate medical education (GME) office is notified, if faculty are
      informed, or if resident privileges are limited. Descriptive data are reported.
      RESULTS: Eighty-one of 160 PDs responded. An official policy on remediation
      and/or probation was reported by 41 (50.6%) programs. The status of informal
      remediation is used by 73 (90.1%), 80 (98.8%) have formal remediation, 40 (49.4%)
      have informal probation, and 79 (97.5%) have formal probation. There was great
      variation among PDs in the management and definition of remediation and
      probation. Between 81 and 86% of programs place an official letter into the
      resident's file regarding formal remediation and probation. However, only about
      50% notify the GME office when a resident is placed on formal remediation. There
      were no statistical differences between MK and non-MK remediation practices.
      CONCLUSIONS: There is significant variation among EM programs regarding the
      process of remediation and probation. The definition of these terms and the
      actions triggered are variable across programs. Based on these findings,
      suggestions toward a standardized approach for remediation and probation in GME
      programs are provided.

PMID- 25565493
TI  - Hot off the press: Assessing older adult fall risk in the emergency department.

PMID- 25565494
TI  - Towards better digital pathology workflows: programming libraries for high-speed
      sharpness assessment of Whole Slide Images.
AB  - BACKGROUND: Since microscopic slides can now be automatically digitized and
      integrated in the clinical workflow, quality assessment of Whole Slide Images
      (WSI) has become a crucial issue. We present a no-reference quality assessment
      method that has been thoroughly tested since 2010 and is under implementation in
      multiple sites, both public university-hospitals and private entities. It is part
      of the FlexMIm R&D project which aims to improve the global workflow of digital
      pathology. For these uses, we have developed two programming libraries, in Java
      and Python, which can be integrated in various types of WSI acquisition systems,
      viewers and image analysis tools. METHODS: Development and testing have been
      carried out on a MacBook Pro i7 and on a bi-Xeon 2.7GHz server. Libraries
      implementing the blur assessment method have been developed in Java, Python, PHP5
      and MySQL5. For web applications, JavaScript, Ajax, JSON and Sockets were also
      used, as well as the Google Maps API. Aperio SVS files were converted into the
      Google Maps format using VIPS and Openslide libraries. RESULTS: We designed the
      Java library as a Service Provider Interface (SPI), extendable by third parties.
      Analysis is computed in real-time (3 billion pixels per minute). Tests were made
      on 5000 single images, 200 NDPI WSI, 100 Aperio SVS WSI converted to the Google
      Maps format. CONCLUSIONS: Applications based on our method and libraries can be
      used upstream, as calibration and quality control tool for the WSI acquisition
      systems, or as tools to reacquire tiles while the WSI is being scanned. They can
      also be used downstream to reacquire the complete slides that are below the
      quality threshold for surgical pathology analysis. WSI may also be displayed in a
      smarter way by sending and displaying the regions of highest quality before other
      regions. Such quality assessment scores could be integrated as WSI's metadata
      shared in clinical, research or teaching contexts, for a more efficient medical
      informatics workflow.

PMID- 25565496
TI  - Systematic review of retention of pediatric patients on HIV treatment in low and
      middle-income countries 2008-2013.
AB  - OBJECTIVES: There are several published systematic reviews of adult retention in
      care after antiretroviral therapy (ART) initiation among adults, but limited
      information on pediatric retention. DESIGN: Systematic review of pediatric
      retention on ART in low and middle-income countries during 2008-2013. METHODS: We
      estimated all-cause attrition (death and loss to follow-up) and retention for
      pediatric patients receiving first-line ART in routine settings. We searched
      PubMed, Embase, Cochrane Register, and ISI Web of Science (January 2008-January
      2014) and abstracts from AIDS and IAS (2008-2013). We estimated mean retention
      across cohorts using simple averages; interpolated any time period not reported
      to, up to the last period reported; summarized total retention in the population
      using Kaplan-Meier survival curves; and compared pediatric to adult retention.
      RESULTS: We found 39 reports of retention in 45 patient cohorts and 55 904
      patients in 23 countries. Among them, 37% of patients not retained in care were
      known to have died and 63% were lost to follow-up. Unweighted averages of
      reported retention were 85, 81, and 81% at 12, 24, and 36 months after ART
      initiation. From life-table analysis, we estimated retention at 12, 24, and 36
      months at 88, 72, and 67%. We estimated 36-month retention at 66% in Africa and
      74% in Asia. CONCLUSION: Pediatric ART retention was similar to that among
      adults. There were limited data from Asia, only one study from Latin America and
      the Caribbean, and no data from Eastern Europe, Central Asia, or the Middle East.

PMID- 25565495
TI  - Effects of a social network HIV/STD prevention intervention for MSM in Russia and
      Hungary: a randomized controlled trial.
AB  - OBJECTIVE: To test a novel social network HIV risk-reduction intervention for MSM
      in Russia and Hungary, where same-sex behavior is stigmatized and men may best be
      reached through their social network connections. DESIGN: A two-arm trial with 18
      sociocentric networks of MSM randomized to the social network intervention or
      standard HIV/STD testing/counseling. SETTING: St. Petersburg, Russia and
      Budapest, Hungary. PARTICIPANTS: Eighteen 'seeds' from community venues invited
      the participation of their MSM friends who, in turn, invited their own MSM
      friends into the study, a process that continued outward until eighteen three
      ring sociocentric networks (mean size = 35 members, n = 626) were recruited.
      INTERVENTION: Empirically identified network leaders were trained and guided to
      convey HIV prevention advice to other network members. MAIN OUTCOME AND MEASURES:
      Changes in sexual behavior from baseline to 3-month and 12-month follow-up, with
      composite HIV/STD incidence, measured at 12 months to corroborate behavior
      changes. RESULTS: There were significant reductions between baseline, first
      follow-up, and second follow-up in the intervention versus comparison arm for
      proportion of men engaging in any unprotected anal intercourse (UAI) (P = 0.04);
      UAI with a nonmain partner (P = 0.04); and UAI with multiple partners (P =
      0.002). The mean percentage of unprotected anal intercourse acts significantly
      declined (P = 0.001), as well as the mean number of UAI acts among men who
      initially had multiple partners (P = 0.05). Biological HIV/STD incidence was 15%
      in comparison condition networks and 9% in intervention condition networks.
      CONCLUSION: Even where same-sex behavior is stigmatized, it is possible to reach
      MSM and deliver HIV prevention through their social networks.

PMID- 25565497
TI  - Delayed liver fibrosis in HTLV-2-infected patients co-infected with HIV-1 and
      hepatitis C virus with suppressive antiretroviral therapy.
AB  - OBJECTIVES: The absence of direct clinical symptoms clearly associated to HTLV-2
      infection may partially explain an underestimate of the real HTLV-2 prevalence
      rate and its effects in patients concurrently infected with HIV-1 and hepatitis C
      virus (HCV). Hence, to date, the influence of HTLV-2 on hepatic fibrosis has been
      poorly studied. DESIGN: Retrospective study to clarify the influence of HTLV-2
      infection in HCV infection and hepatic fibrosis among patients co-infected with
      HIV-1. METHODS: This is a comparative cohort study including 39 HTLV-2-HIV-1-HCV
      co-infected patients and 42 HIV-1-HCV co-infected patients conducted in a
      tertiary care hospital. They were evaluated for transaminase levels, hepatic
      fibrosis stage, interleukin (IL)-28B genotype, Th1/Th2/Th17 cytokine levels,
      immune activation, inflammation, and microbial translocation. RESULTS: HTLV-2-HIV
      1-HCV co-infected patients had lower alanine aminotransferase levels (P = 0.023)
      and hepatic fibrosis (P = 0.012), compared to HIV-1-HCV co-infected patients.
      Moreover, Kaplan-Meier survival analysis showed a delay in hepatic fibrosis
      development for up to 5 years (P = 0.032). HTLV-2-HIV-1-HCV co-infected patients
      also had higher Th1/Th2 ratio (interferon gamma/IL-4 ratio, P = 0.043; tumor
      necrosis factor alpha/IL-4 ratio, P = 0.010) and Th17 response (P = 0.015),
      whereas lower CD8 T-cell activation (P = 0.017) and lipopolysaccharide level (P =
      0.001). CONCLUSION: Findings strongly support that HTLV-2 co-infection might
      delay fibrosis development in HCV-HIV-1 co-infected patients.

PMID- 25565498
TI  - Mixed membership trajectory models of cognitive impairment in the multicenter
      AIDS cohort study.
AB  - OBJECTIVE: The longitudinal trajectories that individuals may take from a state
      of normal cognition to HIV-associated dementia are unknown. We applied a novel
      statistical methodology to identify trajectories to cognitive impairment, and
      factors that affected the 'closeness' of an individual to one of the canonical
      trajectories. DESIGN: The Multicenter AIDS Cohort Study (MACS) is a four-site
      longitudinal study of the natural and treated history of HIV disease among gay
      and bisexual men. METHODS: Using data from 3892 men (both HIV-infected and HIV
      uninfected) enrolled in the neuropsychology substudy of the MACS, a Mixed
      Membership Trajectory Model (MMTM) was applied to capture the pathways from
      normal cognitive function to mild impairment to severe impairment. MMTMs allow
      the data to identify canonical pathways and to model the effects of risk factors
      on an individual's 'closeness' to these trajectories. RESULTS: First, we
      identified three distinct trajectories to cognitive impairment: 'normal aging'
      (low probability of mild impairment until age 60); 'premature aging' (mild
      impairment starting at age 45-50); and 'unhealthy' (mild impairment in 20s and
      30s) profiles. Second, clinically defined AIDS, and not simply HIV disease, was
      associated with closeness to the premature aging trajectory, and, third,
      hepatitis-C infection, depression, race, recruitment cohort and confounding
      conditions all affected individual's closeness to these trajectories. CONCLUSION:
      These results provide new insight into the natural history of cognitive
      dysfunction in HIV disease and provide evidence for a potential difference in the
      pathophysiology of the development of cognitive impairment based on trajectories
      to impairment.

PMID- 25565499
TI  - Plasma interleukin-18 levels are a biomarker of innate immune responses that
      predict and characterize tuberculosis-associated immune reconstitution
      inflammatory syndrome.
AB  - BACKGROUND: Tuberculosis-associated immune reconstitution inflammatory syndrome
      (TB-IRIS) is a substantial problem in HIV/TB coinfected patients commencing
      antiretroviral therapy (ART). The immunopathogenesis of TB-IRIS includes
      increased production of proinflammatory chemokines and cytokines, including
      interleukin-18, which is a signature cytokine of the nucleotide-binding domain
      and leucine-rich repeat pyrin containing protein-3 inflammasome. We compared
      plasma levels of interleukin-18 and other biomarkers of monocyte/macrophage
      activation in the prediction and characterization of TB-IRIS. METHODS: Biomarkers
      were assayed pre-ART and during TB-IRIS, or equivalent time-point, in a case
      control study of Malaysian HIV patients with paradoxical or unmasking TB-IRIS (n
      = 15), TB no IRIS (n = 14), and no TB or IRIS (n = 15). Findings for interleukin
      18 were verified in another cohort of patients with paradoxical TB-IRIS (n = 26)
      and their controls (n = 22) from India. RESULTS: Interleukin-18 was higher in TB
      IRIS patients pre-ART and during the event in both Malaysian patients (P <
      0.0001) and Indian patients (P < 0.01). CXCL10 was higher pre-ART (P < 0.001),
      mainly in paradoxical TB-IRIS patients, and during TB-IRIS (P < 0.001), whereas
      CXCL8 was only higher during TB-IRIS (P < 0.001). Soluble(s) CD14 was increased
      in all patients with HIV/TB coinfection pre-ART and during TB-IRIS or equivalent
      time-point, compared with patients without TB. In contrast, interferon-gamma was
      lower before and during TB-IRIS. By receiver operating curve analysis, CXCL10,
      and/or interleukin-18 pre-ART were predictive of TB-IRIS. CONCLUSION: Plasma
      interleukin-18 levels pre-ART are candidate biomarkers for predicting paradoxical
      and unmasking TB-IRIS and should be investigated for risk stratification and
      elucidation of disease pathogenesis.

PMID- 25565501
TI  - Prognosis and course of pain in patients with chronic non-specific low back pain:
      A 1-year follow-up cohort study.
AB  - BACKGROUND: It remains unclear to what extent patients recover from chronic non
      specific low back pain (NSLBP). The objective of this study was to determine (1)
      the course of chronic NSLBP in tertiary care and (2) which factors predicted 5-
      and 12-month outcomes. METHODS: This prospective study includes 1760 chronic
      NSLBP patients from a rehabilitation clinic (mean age 40.1 years, SD 10.6). After
      baseline measurement, patients followed a 2-month multidisciplinary therapy
      programme; evaluation took place at 2, 5 and 12 months post baseline. Recovery
      was defined as (1) relative recovery [30% improvement on the pain, visual
      analogue scale (VAS) compared with baseline] and (2) absolute recovery (VAS pain
      <= 10 mm). The multivariate logistic regression analysis included 23 baseline
      characteristics. RESULTS: Patient-reported intensity of back pain decreased from
      55.5 (SD 23.0) at baseline to 37.0 (SD 23.8), 35.3 (SD 26.1) and 32.3 (SD 26.9)
      at 2-, 5- and 12-month follow-up, respectively. Younger age, back pain at
      baseline, no psychological/physical dysfunction (Symptom Check List-90, item 9),
      and higher baseline scores on the physical component scale and mental component
      scale of quality of life (Short Form-36) were positively associated with recovery
      at 5 and 12 months. At 5-month follow-up, higher work participation at baseline
      was also a prognostic factor for both definitions of recovery. At 12-month follow
      up, having co-morbidity was predictive for both definitions. CONCLUSION: The
      results of this study indicate that in chronic NSLBP patients, bio-psychosocial
      prognostic factors may be important for clinicians when predicting recovery in
      back pain intensity during a 1-year period.

PMID- 25565500
TI  - Plaque burden in HIV-infected patients is associated with serum intestinal
      microbiota-generated trimethylamine.
AB  - OBJECTIVE: Some intestinal microbiota-generated metabolites of
      phosphatidylcholine are recognized to be proatherogenic. As the HIV population is
      vulnerable to cardiovascular disease and can develop intestinal dysbiosis
      associated with systemic inflammation, we investigated the novel relationship
      between microbiota-derived metabolites of phosphatidylcholine and coronary
      atherosclerosis in HIV. DESIGN/METHODS: One hundred and fifty-five HIV-infected
      and 67 non-HIV-infected individuals without known history of cardiovascular
      disease were previously recruited to assess coronary plaque by computed
      tomography angiography. In the current study, we evaluate whether serum choline,
      trimethylamine (TMA), or trimethylamine-N-oxide (TMAO) levels are associated with
      plaque features. RESULTS: Young, asymptomatic HIV-infected patients (age 47 +/- 7
      years) demonstrated significantly higher prevalence of plaque (53 vs. 35%, P =
      0.01) and number of total plaque segments (1.8 +/- 2.5 vs. 1.2 +/- 2.2, P = 0.03)
      when compared with well matched noninfected individuals with similar
      comorbidities. TMA was significantly associated with calcium score (r = 0.22, P =
      0.006), number of total (r = 0.20, P = 0.02) and calcified (r = 0.18, P = 0.03)
      plaque segments, and calcium plaque volume (r = 0.19, P = 0.02) and mass (r =
      0.22, P = 0.009) in the HIV cohort only. In multivariate modeling among HIV
      infected patients, TMA remained significantly associated with calcium score (P =
      0.008), number of total (P = 0.005) and calcified (P = 0.02) plaque segments, and
      calcium plaque volume (P = 0.01) and mass (P = 0.007), independent of Framingham
      risk score. In contrast, there was no association of TMAO to coronary plaque
      features in either cohort. CONCLUSION: A link between TMA and atherosclerosis has
      not previously been established. The current study suggests that TMA may be a
      nontraditional risk factor related to the number of plaque segments and severity
      of calcified plaque burden in HIV.

PMID- 25565502
TI  - Studies on the stability of preservatives under subcritical water conditions.
AB  - OBJECTIVE: The goal of this work was to further validate the subcritical water
      chromatography (SBWC) methods for separation and analysis of preservatives
      through the evaluation of analyte stability in subcritical water. METHODS: In
      this study, the degradation of preservatives was investigated at temperatures of
      100-200 degrees C using two different approaches. First, the peak areas obtained
      by SBWC at high temperatures were compared with those achieved using the
      traditional high-performance liquid chromatography (HPLC) at 25 degrees C. In the
      second approach, several preservatives and water were loaded into a vessel and
      heated at high temperatures for 30 or 60 min. The heated mixtures were then
      analysed by GC/MS to determine the stability of preservatives. RESULTS: The t-
      and F-test on the results of the first approach reveal that the peak areas
      achieved by HPLC and SBWC are not significantly different at the 95% confidence
      level, meaning that the preservatives studied are stable during the high
      temperature SBWC runs. Although the results of the second approach show
      approximately 10% degradation of preservatives into mainly p-hydroxybenzoic acid
      and phenol at 200 degrees C, the preservatives studied are stable at 100 and 150
      degrees C. This is in good agreement with the validation results obtained by the
      first approach. CONCLUSION: The findings of this work confirm that SBWC methods
      at temperatures up to 150 degrees C are reliable for separation and analysis of
      preservatives in cosmetic and other samples.

PMID- 25565503
TI  - Global women's health: challenges and opportunities.

PMID- 25565504
TI  - Global women's health in the balance. Preface.

PMID- 25565505
TI  - Global fertility and population trends.
AB  - Over the past several decades, the world and most countries have undergone
      unprecedented demographic change. The most obvious example of this change is the
      rise in human numbers, and there are also important trends in fertility, family
      structure, mortality, migration, urbanization, and population aging. This paper
      summarizes past trends and projections in fertility and population. After
      reaching 2.5 billion in 1950, the world population grew rapidly to 7.2 billion in
      2013 and the projections expect this total to be 10.9 billion by 2100. World
      regions differ widely in their demographic trends, with rapid population growth
      and high fertility continuing in the poorest countries, particularly in sub
      Saharan Africa, while population decline, population aging, and very low
      fertility are now a key concern in many developed countries. These trends have
      important implications for human welfare and are of interest to policy makers.
      The conclusion comments briefly on policy options to address these adverse
      trends. 

PMID- 25565507
TI  - Access to infertility care in the developing world: the family promotion gap.
AB  - Infertility in resource-poor settings is an overlooked global health problem.
      Although scarce health care resources must be deployed thoughtfully,
      prioritization of resources may be different for recipient and donor countries,
      the latter of whom focus on maternal health care, prevention, and family
      planning. For women and couples with involuntary childlessness, the negative
      psychosocial, sociocultural, and economic consequences in low-income countries
      are severe, possibly more so than in most Western societies. Despite the local
      importance of infertility, few resources are committed to help advance
      infertility care in regions like sub-Saharan Africa. The worldwide prevalence of
      infertility is remarkably similar across low-, middle-, and high-income
      countries. The World Health Organization (WHO) recognizes infertility as a global
      health problem and established universal access to reproductive health care as
      one of the United Nation's Millennium Developmental Goals for 2015. Currently,
      access to infertility care is varied and is usually only attainable by the very
      wealthy in low-income countries. We provide an overview on the current state of
      access to infertility care in low-income countries such as in sub-Saharan Africa
      and a rationale for providing comprehensive reproductive care and possible
      solutions for providing cost-effective infertility services in these settings. 

PMID- 25565506
TI  - Unmet need for family planning: past achievements and remaining challenges.
AB  - Globally, the percentage of married fecund women with unmet need-who use no
      contraceptive method despite wishing to avoid childbearing for two years or more
      fell from 22% in 1970 to 12% in 2010. Substantial health, economic and
      environmental, and demographic benefits have resulted from this change. Promotion
      of contraception is one of the great success stories of the past 50 years.
      However, unmet need remains high in sub-Saharan Africa, at 25%, because of
      insufficient knowledge of methods, social opposition, and fear of health effects.
      In addition to obvious factors such as political commitment and adequate funding,
      success in this region will require improvement in continuation of use and the
      range of available methods. 

PMID- 25565508
TI  - Towards ending preventable maternal deaths by 2035.
AB  - Maternal mortality has been reduced by half from 1990 to 2010, yet a woman in sub
      Saharan Africa has a lifetime risk of maternal death of 1 in 39 compared with
      around 1 in 10,000 in industrialized countries. Annual rates of reduction of
      maternal mortality of over 10% have been achieved in several countries. Highly
      cost-effective interventions exist and are being scaled up, such as family
      planning, emergency obstetric and newborn care, quality service delivery,
      midwifery, maternal death surveillance and response, and girls' education;
      however, coverage still remains low. Maternal mortality reduction is now high on
      the global agenda. We examined scenarios of reduction of maternal mortality by
      2035. Ending preventable maternal deaths could be achieved in nearly all
      countries by 2035 with challenging yet realistic efforts: (1) massive scaling-up
      and skilling up of human resources for family planning and maternal health; (2)
      reaching every village in every district and every urban slum toward universal
      health coverage; (3) enhanced financing; (4) knowledge for action: enhanced
      monitoring, accountability, evaluation, and R&D. 

PMID- 25565509
TI  - Communicable diseases.
AB  - Globally, infectious diseases often disproportionately affect women, and have
      implications for the health of future generations. The human immunodeficiency
      virus (HIV), tuberculosis, malaria, and schistosomiasis are four such pathogens.
      Infection with these organisms has a broad impact on maternal child health in
      many areas of the developing world, and global initiatives to control these
      diseases will significantly improve the health of generations to come. 

PMID- 25565510
TI  - Noncommunicable diseases.
AB  - Noncommunicable diseases (NCDs), long considered diseases of little significance
      to global health, represent the greatest threat to economic development and human
      health. The main NCDs-diabetes, cancer, cardiovascular disease, and chronic
      respiratory disease-are the world's number one killer and bear the greatest
      burden on the poor. On September 19-20, 2011, the United Nations General Assembly
      (UNGA) convened a high-level meeting (HLM) on the Prevention and Control of Non
      Communicable Diseases. The only other HLM held on a health issue in the past had
      been in 2001 for HIV/AIDS and resulted in ambitious targets, global surveillance,
      and billions of dollars in aid. The 2011 HLM for NCDs did not measure up to the
      previous meeting in funding, targets, or advocacy but gave birth to a series of
      commitments in the form of a political declaration. In this article, we discuss
      the extent to which NCD is effecting the global population, what has and has not
      transpired since the 2011 HLM, and what lies ahead if we are to successfully
      tackle this growing burden of disease before it grows beyond our reach. 

PMID- 25565511
TI  - Female genital cutting: impact on women's health.
AB  - More than 130 million women worldwide have undergone female genital cutting
      (FGC). FGC is practiced in parts of Africa and Asia, in societies with various
      cultures and religions. Reasons for the continuing practice of FGC include rite
      of passage, preserving chastity, ensuring marriageability, religion, hygiene,
      improving fertility, and enhancing sexual pleasure for men. The World Health
      Organization has classified FGC into four types depending on the extent of tissue
      removed. Immediate complications include hemorrhage, infection, sepsis, and
      death. Long-term complications include pain, scarring, urinary issues, and poor
      obstetric and neonatal outcomes. Efforts are being made nationally and
      internationally to eradicate this practice. In December 2012, the UN General
      Assembly accepted a resolution on the elimination of FGC. Although it is illegal
      to perform FGC in the United States, women from countries where the practice
      occurs have been and are still immigrating here. Many enter as refugees from war
      torn, famine-stricken, or politically unstable countries. They bring along with
      them their cultural pride, health complications, and fears of being judged when
      visiting a health provider. A deeper understanding of the history, cultural
      beliefs, medical complications, and methods of surgical reconstruction is
      necessary to provide culturally and linguistically competent care to this unique
      group of women. 

PMID- 25565512
TI  - Urinary fistula and incontinence.
AB  - It is estimated that as many as 3.5 million women worldwide suffer from obstetric
      urinary fistula. This public health tragedy is a result of obstructed labor and
      inadequate access to health care, and its eradication lies in prevention and
      treatment. Efforts at prevention should be made through targeted education and
      public intervention for improved nutrition, access to health care, and women's
      social status. Diagnosis and treatment in limited resource settings can occur,
      and there are specific recommendations regarding nonsurgical and surgical
      approaches to care. Treatment success may be complicated by social,
      psychological, and clinical factors, with reintegration a primary concern for
      this group of women. 

PMID- 25565513
TI  - The health of women and girls: how can we address gender equality and gender
      equity?
AB  - This article focuses on the health of women and girls, and the role of addressing
      gender inequalities experienced by women and girls. The health of both males and
      females is influenced by sex, or biological factors, and gender, or socially
      constructed influences, including gender differences in the distribution and
      impact of social determinants of health, access to health promoting resources,
      health behaviors and gender discourse, and the ways in which health systems are
      organized and financed, and how they deliver care. Various strategies to address
      the health of women and girls have been developed at intergovernmental, regional,
      and national level, and by international nongovernmental organizations. These
      include vertical programs which aim to target specific health risks and deliver
      services to meet women and girl's needs, and more cross-cutting approaches which
      aim at "gender" policy making. Much of this work has developed following the
      adoption of gender mainstreaming principles across different policy arenas and
      scales of policy making, and this article reviews some of these strategies and
      the evidence for their success, before concluding with a consideration of future
      directions in global policy. 

PMID- 25565517
TI  - In the best of health.

PMID- 25565524
TI  - Welcome to the New Blue Journal.

PMID- 25565525
TI  - The AsMA Journal: making a difference in aerospace medicine.

PMID- 25565523
TI  - Behavioural effects of tourism on oceanic common dolphins, Delphinus sp., in New
      Zealand: the effects of Markov analysis variations and current tour operator
      compliance with regulations.
AB  - Common dolphins, Delphinus sp., are one of the marine mammal species tourism
      operations in New Zealand focus on. While effects of cetacean-watching activities
      have previously been examined in coastal regions in New Zealand, this study is
      the first to investigate effects of commercial tourism and recreational vessels
      on common dolphins in an open oceanic habitat. Observations from both an
      independent research vessel and aboard commercial tour vessels operating off the
      central and east coast Bay of Plenty, North Island, New Zealand were used to
      assess dolphin behaviour and record the level of compliance by permitted
      commercial tour operators and private recreational vessels with New Zealand
      regulations. Dolphin behaviour was assessed using two different approaches to
      Markov chain analysis in order to examine variation of responses of dolphins to
      vessels. Results showed that, regardless of the variance in Markov methods,
      dolphin foraging behaviour was significantly altered by boat interactions.
      Dolphins spent less time foraging during interactions and took significantly
      longer to return to foraging once disrupted by vessel presence. This research
      raises concerns about the potential disruption to feeding, a biologically
      critical behaviour. This may be particularly important in an open oceanic
      habitat, where prey resources are typically widely dispersed and unpredictable in
      abundance. Furthermore, because tourism in this region focuses on common dolphins
      transiting between adjacent coastal locations, the potential for cumulative
      effects could exacerbate the local effects demonstrated in this study. While the
      overall level of compliance by commercial operators was relatively high, non
      compliance to the regulations was observed with time restriction, number or speed
      of vessels interacting with dolphins not being respected. Additionally,
      prohibited swimming with calves did occur. The effects shown in this study should
      be carefully considered within conservation management plans, in order to reduce
      the risk of detrimental effects on common dolphins within the region. 

PMID- 25565522
TI  - Double-strand break repair on sex chromosomes: challenges during male meiotic
      prophase.
AB  - During meiotic prophase, DNA double-strand break (DSB) repair-mediated homologous
      recombination (HR) occurs for exchange of genetic information between homologous
      chromosomes. Unlike autosomes or female sex chromosomes, human male sex
      chromosomes X and Y share little homology. Although DSBs are generated throughout
      male sex chromosomes, homologous recombination does not occur for most regions
      and DSB repair process is significantly prolonged. As a result, male sex
      chromosomes are coated with many DNA damage response proteins and form a unique
      chromatin structure known as the XY body. Interestingly, associated with the
      prolonged DSB repair, transcription is repressed in the XY body but not in
      autosomes, a phenomenon known as meiotic sex chromosome inactivation (MSCI),
      which is critical for male meiosis. Here using mice as model organisms, we
      briefly summarize recent progress on DSB repair in meiotic prophase and focus on
      the mechanism and function of DNA damage response in the XY body. 

PMID- 25565526
TI  - Intraocular and intracranial pressures during head-down tilt with lower body
      negative pressure.
AB  - BACKGROUND: Seven astronauts after 6-mo missions to the International Space
      Station showed unexpected vision problems. Lumbar punctures performed in the four
      astronauts with optic disc edema showed moderate elevations of cerebral spinal
      fluid pressure after returning to Earth. We hypothesized that lower body negative
      pressure (LBNP) imposed during head-down tilt (HDT) would reduce intraocular
      pressure (IOP) and transcranial ultrasound pulse amplitude, a noninvasive
      intracranial pressure (ICP) surrogate. METHODS: Participating in this study were
      25 normal healthy nonsmoking volunteers (mean age: 36 yr). Subjects were
      positioned supine (5 min), sitting (5 min), 15 degrees  whole body HDT (5 min),
      and 10 min of HDT with LBNP (25 mmHg). The order of HDT and HDT+LBNP tests was
      balanced. Right and left IOP, transcranial ultrasound pulse amplitude, arm blood
      pressure, and heart rate were measured during the last minute (steady state) of
      each testing condition. RESULTS: IOP significantly decreased from supine to
      sitting posture by 3.2 +/- 1.4 mmHg (mean +/- SD: N = 25), and increased by 0.9
      +/- 1.3 mmHg from supine to the HDT position. LBNP during HDT significantly
      lowered IOP to supine levels. In addition, LBNP significantly reduced
      transcranial ultrasound pulse amplitudes by 38% as compared to the HDT condition
      (N = 9). Sitting mean blood pressure (BP) was significantly higher (+5 mmHg) than
      BP values after 10 min of LBNP during HDT. However, heart rate was not
      significantly different across all conditions. DISCUSSION: These data suggest
      that short duration exposures to LBNP attenuate HDT-induced increases in IOP and
      ICP. Macias BR, Liu JHK, Grande-Gutierrez N, Hargens AR. Intraocular and
      intracranial pressures during head-down tilt with lower body negative pressure.

PMID- 25565527
TI  - Excessive iron and weightlessness effects on the femurs and livers of rats.
AB  - BACKGROUND: Weightlessness results in negative physiological changes. Excessive
      iron in organisms likewise leads to numerous damages. In this study, we
      investigated the effect of a combination of iron overload and weightlessness
      simulated by tail-suspending on rats. METHODS: Male Wistar rats were randomly
      divided into four groups: control (CON), iron overload (IO), simulated
      weightlessness (SW), and iron overload plus simulated weightlessness (IO+SW).
      After the experiment, the rats were evaluated through routine blood, serum
      ferritin, histology, and micro-computed tomography analyses. RESULTS: As compared
      to CON, a combination of IO and SW resulted in a 15.9% loss of rat bodyweight
      versus treatment with each alone (3.3% in IO, 11.7% in SW group). Although iron
      overload is mainly responsible for an increase in hemoglobin (4.7% in IO the
      group) and serum ferritin (71.7% in IO group) concentration, simulated
      weightlessness facilitates such increase (5.3% and 118.4% in IO + SW group,
      respectively). Similarly, iron overload resulted in severe iron deposition on the
      liver and spleen, and the deposition became more serious in the combined model.
      In contrast, the simulated weightlessness is mainly responsible for the damage to
      the femur. DISCUSSION: All the results demonstrated that the combined conditions
      exhibited a significantly different effect on rats from those with either
      simulated weightlessness or iron overload alone, and that these different effects
      are organ-dependent. Wang A, Zang J, Wang J, Nie G, Zhao G, Chen B. Excessive
      iron and weightlessness effects on the femurs and livers of rats.

PMID- 25565528
TI  - Physiological effects of positive pressure breathing with pure oxygen and a low
      oxygen gas mixture.
AB  - INTRODUCTION: Positive pressure breathing (PPB) can cause circulatory dysfunction
      due to peripheral pooling of blood. This study explored a better way at ground
      level to simulate pure oxygen PPB at 59,055 ft (18,000 m) by comparing the
      physiological changes during PPB with pure oxygen and low oxygen at ground level.
      METHODS: Six subjects were exposed to 3 min of 69-mmHg PPB and 3 min of 59-mmHg
      PPB with pure oxygen and low oxygen while wearing the thoracic counterpressure
      jerkin inflated to 1* breathing pressure and G-suit inflated to 3 and 4*
      breathing pressure. Stroke volume (SV), cardiac output (CO), heart rate (HR), and
      peripheral oxygen saturation (Spo2) were measured. Subjects completed a
      simulating flying task (SFT) during 3-min PPB and scores were recorded. RESULTS:
      HR and SV responses differed significantly between breathing pure oxygen and low
      oxygen. CO response was not significantly different for pure oxygen and low
      oxygen, the two levels of PPB, and the two levels of G-suit pressure. Spo2
      declined as a linear function of time during low-oxygen PPB and there was a
      significant difference in Spo2 response for the two levels of PPB. The average
      score of SFT during pure oxygen PPB was 3970.5 +/- 1050.4, which was
      significantly higher than 2708.0 +/- 702.7 with low oxygen PPB. CONCLUSIONS:
      Hypoxia and PPB have a synergistic negative effect on both the cardiovascular
      system and SFT performance. PPB with low oxygen was more appropriate at ground
      level to investigate physiological responses during PPB and evaluate the
      protective performance of garments. Liu X, Xiao H, Shi W, Wen D, Yu L, Chen J.
      Physiological effects of positive pressure breathing with pure oxygen and a low
      oxygen gas mixture.

PMID- 25565529
TI  - Dodecafluoropentane (DDFPe) and decompression sickness-related mortality in rats.
AB  - INTRODUCTION: Perfluorocarbon (PFC) formulations can be a useful adjunct
      treatment for decompression sickness (DCS) when staged decompression procedures
      cannot be followed due to time constraints or lack of equipment. The benefit of
      PFC treatment is believed to result from its ability to transport more dissolved
      gas than can be transported by blood alone. Dodecylfluoropentane (DDFPe) is a
      unique nanodroplet compound that expands into a gaseous state when exposed to
      physiological temperatures, resulting in a higher dissolved gas-carrying capacity
      than standard PFC formulations. METHODS: We investigated the efficacy of DDFPe in
      reducing morbidity and mortality in a rat model of severe DCS. Male Sprague
      Dawley rats (250-280 g) were compressed to 210 fsw for 60 min before rapid
      decompression. Animals were immediately injected with 2% DDFPe (0.07 ml . kg(-1),
      0.5 ml . kg(-1), 1.0 ml . kg(-1)) or saline, and were transferred to a 100% O2
      environment for 30 min. RESULTS: Of the animals in the saline group, 47% (18/38)
      did not survive the decompression event, while ~98% (46/47) of the animals in the
      DDFPe group did not survive. Of the animals that died during the observation
      period, the saline group survived on average 89% longer than DDFPe treated
      animals. Seizures occurred in 42% of the DDFPe group vs. 16% in the saline group.
      Histological analysis revealed the presence of large, multifocal gas emboli in
      the liver and heart of DDFPe treated animals. CONCLUSIONS: We conclude that DDFPe
      is not an effective nonrecompressive treatment for DCS in rodents. Sheppard RL,
      Regis DP, Mahon RT. Dodecafluoropentane (DDFPe) and decompression sickness
      related mortality in rats.

PMID- 25565530
TI  - Repeated apneas and hypercapnic ventilatory response before and after apnea
      training.
AB  - BACKGROUND: Habitual exposure to carbon dioxide (CO2) is expected, but it is not
      proven, to dull ventilatory sensitivity to co2 by reducing hypercapnic
      ventilatory response (HCVR) as it is expressed by the slope of the derived
      response curve (CO2 sensitivity: DeltaVE/DeltaPetCO2). It was hypothesized that
      HCVR is decreased by repeated breath hold maximal efforts (RBHE) before and after
      apnea training in comparison with no training and the control condition. METHODS:
      Two groups of breath holders, a control (CBH) group and novices to breath hold
      activities (NBH), visited the laboratory on four different occasions. In the
      first visit, subjects performed a HCVR test, whereas in the second visit they
      completed five successive RBHE separated by 2-min intervals. Another HCVR test
      was performed 2 min after cessation of the last apnea. For the next 14 d, only
      the NBH group trained by performing daily five RBHE separated by 2-min intervals.
      Subsequently, in a third and a fourth condition, subjects repeated the
      experimental protocol of the second and first visit. RESULTS: Although breath
      hold time (BHT) increased after apnea training in the NBH group by ~46%, CO2
      sensitivity slopes were not different among experimental conditions and groups
      (2.8 0.3, 2.9 0.4 L min(1) mmHg(1) in the CBH and 2.7 0.5, 2.7 0.3 L min(1)
      mmHg(1) in the NBH during the second and third visit, respectively). CONCLUSION:
      HCVR after five RBHE or 14 d of apnea training was not decreased despite the
      achieved BHT enhancement. Hypercapnic dullness of ventilation is a complex
      biological process which takes more than 14 d of training to develop. Bourdas DI,
      Tsakiris TS, Pavlakis KI, Triantafillou DV, Geladas ND. Repeated apneas and
      hypercapnic ventilatory response before and after apnea training.

PMID- 25565531
TI  - Prolonged restricted sitting effects in UH-60 helicopters.
AB  - INTRODUCTION: Advances in flight technologies and the demand for long-range
      flight have increased mission lengths for U.S. Army Black Hawk UH-60 crewmembers.
      Prolonged mission times have increased reports of pilot discomfort and symptoms
      of paresthesia thought to be due to UH-60 seat design and areas of locally high
      pressure. Discomfort created by the seat-system decreases situational awareness,
      putting aviators and support crew at risk of injury. Therefore, the purpose of
      this study was to examine the effects of prolonged restricted sitting in a UH-60
      on discomfort, sensory function, and vascular measures in the lower extremities.
      METHODS: There were 15 healthy men (age = 23.4 +/- 3.1 yr) meeting physical
      flight status requirements who sat in an unpadded, UH-60 pilot's seat for 4 h
      while completing a common cognitive task. During the session, subjective
      discomfort, sensory function, and vascular function were measured. RESULTS:
      Across 4 h of restricted sitting, subjective discomfort increased using the
      Category Partitioning Scale (30.27 point increase) and McGill Pain Questionnaire
      (8.53 point increase); lower extremity sensory function was diminished along the
      S1 dermatome; and skin temperature decreased on both the lateral (2.85 degrees C
      decrease) and anterior (2.78 degrees C decrease) aspects of the ankle.
      DISCUSSION: The results suggest that prolonged sitting in a UH-60 seat increases
      discomfort, potentially through a peripheral nervous or vascular system
      mechanism. Further research is needed to understand the etiology and onset of
      pain and paresthesia during prolonged sitting in UH-60 pilot seats. Games KE,
      Lakin JM, Quindry JC, Weimar WH, Sefton JM. Prolonged restricted sitting effects
      in UH-60 helicopters.

PMID- 25565532
TI  - End tidal CO2 in recreational rebreather divers on surfacing after decompression
      dives.
AB  - INTRODUCTION: Deep dives using rebreather devices result in oxygen exposures that
      carry a risk of cerebral oxygen toxicity. Elevation of arterial CO2 levels
      increases this risk. CO2 retention may occur during the deep working phases of
      dives, but it has not been investigated in 'real world' dives at the end of
      resting decompression when oxygen exposures are peaking, often to levels higher
      than recommended maxima. METHODS: We conducted an observational field study to
      measure end tidal CO2 (Petco2) in divers surfacing after decompression. Sixteen
      rebreather divers conducted two dives and two completed one dive (a total of 34
      dives) to depths ranging from 44-55 msw. Bottom times ranged from 35 to 56 min
      and time spent on decompression ranged from 40 to 92 min. The first breaths on
      reaching the surface after removing the rebreather mouthpiece were taken through
      a portable capnograph. The Petco2 was recorded for the first breath that produced
      a clean capnography trace. Petco2 measurement was repeated for each subject 2-3 h
      after diving to give paired observations. RESULTS: There were no differences
      between mean surfacing Petco2 [36.8 mmHg (SD 3.0)] and the mean Petco2 made later
      after diving [36.9 mmHg (SD 4.0)]. One subject on one dive returned a surfacing
      Petco2 higher than a nominal upper limit of 45 mmHg. DISCUSSION: We found no
      general tendency to CO2 retention during decompression. It is plausible that
      breaching oxygen exposure limits during resting decompression is less hazardous
      than equivalent breaches when exercising at deep depths. Mitchell SJ, Mesley P,
      Hannam JA. End tidal CO2 in recreational rebreather divers on surfacing after
      decompression dives.

PMID- 25565533
TI  - Night vision goggle-induced neck pain in military helicopter aircrew: a
      literature review.
AB  - Neck pain occurs at a significant rate in the military helicopter community. It
      is often attributed to the use of night vision goggles (NVG) and to a number of
      additional factors such as anthropometrics, posture, vibration, mission length,
      physical fitness, and helmet fit or load. A number of research studies have
      addressed many aspects of this epidemic, but an up-to-date and comprehensive
      review of the literature is not currently available. This paper reviews the
      spinal anatomy in general and then summarizes what is known about the incidence
      and prevalence of neck injuries, how the operational environments and equipment
      may contribute to these injuries, and what can be done to address them from a
      prevention and/or rehabilitation perspective. Harrison MF, Coffey B, Albert WJ,
      Fischer SL. Night vision goggle-induced neck pain in military helicopter aircrew:
      a literature review.

PMID- 25565534
TI  - Quantification of color vision using a tablet display.
AB  - BACKGROUND: Accurate color vision is essential for optimal performance in
      aviation and space environments using nonredundant color coding to convey
      critical information. Most color tests detect color vision deficiency (CVD) but
      fail to diagnose type or severity of CVD, which are important to link performance
      to occupational demands. The computer-based Cone Contrast Test (CCT) diagnoses
      type and severity of CVD. It is displayed on a netbook computer for clinical
      application, but a more portable version may prove useful for deployments, space
      and aviation cockpits, as well as accident and sports medicine settings. Our
      purpose was to determine if the CCT can be conducted on a tablet display (Windows
      8, Microsoft, Seattle, WA) using touch-screen response input. METHODS: The CCT
      presents colored letters visible only to red (R), green (G), and blue (B)
      sensitive retinal cones to determine the lowest R, G, and B cone contrast visible
      to the observer. The CCT was measured in 16 color vision normals (CVN) and 16
      CVDs using the standard netbook computer and a Windows 8 tablet display
      calibrated to produce equal color contrasts. RESULTS: Both displays showed 100%
      specificity for confirming CVN and 100% sensitivity for detecting CVD. In CVNs
      there was no difference between scores on netbook vs. tablet displays. G cone
      CVDs showed slightly lower G cone CCT scores on the tablet. CONCLUSIONS: CVD can
      be diagnosed with a tablet display. Ease-of-use, portability, and complete
      computer capabilities make tablets ideal for multiple settings, including
      aviation, space, military deployments, accidents and rescue missions, and sports
      vision. Chacon A, Rabin J, Yu D, Johnston S, Bradshaw T. Quantification of color
      vision using a tablet display.

PMID- 25565535
TI  - Pneumocephalus and neurosurgery in rotary aircrew.
AB  - BACKGROUND: Pneumocephalus secondary to trauma or tumors can have varied symptom
      severity. It is important to recognize and quantify pneumocephalus for medical
      evacuation and treatment. This case presents current recommendations for travel
      in the literature and how they are applicable in returning to flying duties after
      neurosurgical interventions. CASE REPORT: This is the case of a Naval aircrew
      member who developed an osteoma and subsequently periorbital emphysema and
      pneumocephalus. This required medical evacuation from a remote territory, a team
      surgical approach, and later testing to allow him to return to flight duties in
      rotary aircraft. DISCUSSION: A search of the literature did not reveal any
      previous cases of civilian or military flight crew having returned to flying
      duties after pneumocephalus or neurosurgery. Barometric chamber testing was
      performed post-operatively to provide clearance. Literature review revealed mixed
      advice on when one can safely fly commercially after neurosurgery and may be
      applicable in a case series of medical evacuation or future clearance in
      returning to flight duties. Ruddick B, Tomlin J. Pneumocephalus and neurosurgery
      in rotary aircrew.

PMID- 25565539
TI  - Bringing evidence to the practice of human performance.

PMID- 25565540
TI  - You're the Flight Surgeon: sarcoidosis.

PMID- 25565541
TI  - You're the Flight Surgeon: aviator with brief psychotic episode.

PMID- 25565542
TI  - Firsts in space and space medicine.

PMID- 25565544
TI  - Pathologic role of neuronal nicotinic acetylcholine receptors in epileptic
      disorders: implication for pharmacological interventions.
AB  - Accumulating evidence suggests that neuronal nicotinic acetylcholine receptors
      (nAChRs) may play a key role in the pathophysiology of some neurological diseases
      such as epilepsy. Based on genetic studies in patients with epileptic disorders
      worldwide and animal models of seizure, it has been demonstrated that nAChR
      activity is altered in some specific types of epilepsy, including autosomal
      dominant nocturnal frontal lobe epilepsy (ADNFLE) and juvenile myoclonic epilepsy
      (JME). Neuronal nAChR antagonists also have antiepileptic effects in pre-clinical
      studies. There is some evidence that conventional antiepileptic drugs may affect
      neuronal nAChR function. In this review, we re-examine the evidence for the
      involvement of nAChRs in the pathophysiology of some epileptic disorders,
      especially ADNFLE and JME, and provide an overview of nAChR antagonists that have
      been evaluated in animal models of seizure. 

PMID- 25565546
TI  - Revival of physostigmine - a novel HPLC assay for simultaneous determination of
      physostigmine and its metabolite eseroline designed for a pharmacokinetic study
      of septic patients.
AB  - BACKGROUND: Physostigmine, commonly used as an antidote in anticholinergic
      poisoning, is reported to have additional pharmacological effects, such as
      activation of the cholinergic anti-inflammatory pathway in sepsis models. Due to
      the narrow therapeutic range of physostigmine and its metabolite eseroline,
      however, the plasma concentrations of these substances need to be determined so
      as to understand their effect and ensure safety in the treatment of septic
      patients. METHODS: To determine physostigmine and its metabolite eseroline, a
      rapid and sensitive high performance liquid chromatography (HPLC) method has been
      developed and validated. Spiked plasma samples were cleaned up and concentrated
      using a simple liquid-liquid extraction (LLE) procedure with N
      methylphysostigmine as internal standard. Separation was achieved using reversed
      phase HPLC on a Kinetex C18 column with gradient elution and fluorescence
      detection (254 nm excitation/355 nm emission). RESULTS: LLE produced clean
      extracts and a mean recovery of 80.3% for eseroline and 84.9% for physostigmine.
      The HPLC assay revealed a limit of detection (LOD) of 0.025 ng/mL and a lower
      limit of quantification (LLOQ) of 0.05 ng/mL for both analytes. Linearity was
      observed at 0.05-10.0 ng/mL (r2>0.999). Intra- and inter-day precision ranged
      from 0.7% to 6.6%, and intra- and inter-day accuracy 97.5%-110.0%. CONCLUSIONS:
      The presented method is useful for human drug level monitoring of physostigmine
      and eseroline in accordance with current guidelines. Remarkably low plasma
      concentrations can be quantified after LLE with gradient elution and fluorescence
      detection, making this a suitable method for pharmacokinetic studies in a
      clinical setting.

PMID- 25565545
TI  - Fatal hyperkalemia following succinylcholine administration in a child on oral
      propranolol.
AB  - Succinylcholine is one of the most commonly used drugs by anesthesiologists
      worldwide for rapid access to airway both in emergency and elective situations.
      Nonetheless, the very mention of succinylcholine generates the most energetic
      high decibel debate between its users and nonusers. Despite its potential to
      produce a short-acting, ultra-intense neuromuscular block rapidly in seconds, it
      is surrounded by a plethora of side effects and drug interactions. This case
      report is about one such drug interaction of this innocent yet malicious drug,
      which resulted in the death of a 14-year-old girl. Both beta-adrenergic blockers
      and succinylcholine are known to cause hyperkalemia. Life-threatening
      hyperkalemia in susceptible individuals who have been administered
      succinylcholine has the most severe effect on the myocardium and can result in
      asystole with minimal chances of resuscitation. Both succinylcholine and a
      nonselective beta-adrenergic blocker, propranolol, have the propensity to affect
      the transcellular redistribution of potassium which can result in hyperkalemia.
      We advocate cautious use of this drug combination till further studies confirm
      the drug interaction and find the potential triggering factors involved. 

PMID- 25565548
TI  - Trends in publications on complementary and alternative medicine in the medical
      literature.
AB  - BACKGROUND: Public interest in and demand for complementary and alternative
      medicine (CAM) services have increased in recent years throughout the Western
      world. The aim of the study was to assess trends in publications on CAM in the
      medical literature between 1963 and 2012 and to compare them with overall trends
      in publications on medical issues. METHODS: A search of the literature was
      conducted on CAM and integrative medicine using the PubMed and Google Scholar
      search engines with key search terms. RESULTS: Articles on CAM began to appear in
      the medical literature 50 years ago. Over the years there has been an increase in
      the number of publications. On PubMed the increase was from 15,764 to 144,288
      articles from 1963 to 2012. In the decade between 1963 and 1972 publications on
      CAM comprised 0.81% of all the articles appearing in PubMed. Over the course of
      the 50 years, the percentage increased more than twofold to 1.92% from 2003 to
      2012. On Google Scholar there were 27,170 citations related to CAM between 1963
      and 1972. This increased to 2,521,430 between 2003 and 2012. CONCLUSIONS: Over
      the last 50 years there has been an increase in scientific publications on CAM in
      general, and on specific CAM treatments in particular.

PMID- 25565547
TI  - Plasmatic and urinary glycosaminoglycan profile in a patient affected by multiple
      sulfatase deficiency.

PMID- 25565549
TI  - Preliminary validation of Thiel embalmed cadavers for laparoscopic radical
      nephrectomy.
AB  - PURPOSE: This study evaluated face, content, construct validity, and reliability
      of Thiel embalmed cadavers (TEC) as a training tool for transperitoneal
      laparoscopic nephrectomy (TLN). MATERIALS AND METHODS: The study participants
      were prospectively recruited through an advanced laparoscopic renal resection
      teaching skill course. The participants were grouped into: nonexperts (performed
      fewer than 50 TLNs) and experts (performed more than 50 TLNs). All the
      participants performed TLN on TEC, which was video recorded. All participants
      rated their overall experience of performing TLN on TEC with emphasis on realism
      (face validity). The participants were asked to rate the appropriateness of TEC
      for training in TLN (content training). Two experienced laparoscopic surgeons,
      using validated modified Objective Structured Assessment of Technical Skills,
      assessed the individual videos. The parameters studied were: Respect for tissues,
      time and motion, and instrument handling for each step of laparoscopic
      nephrectomy (LN) (construct validity). Test-retest and interrater reliability was
      also evaluated. RESULTS: Twenty-four participants (4 experts and 20 nonexperts)
      took part in this study. The mean overall rating for the experience of TLN on TEC
      was 4.5 (Face Validity). The mean score for the appropriateness of TEC as a
      training tool for TLN was 4.6 (content validity) when evaluated by the four
      experts. The mean scores for the nonexperts and experts using video recordings
      for various variables were: Respect for tissue-1.74 (standard deviation [SD]
      0.62) vs 3.63 (SD-1.06), (P<0.01), time and motion-1.74 (SD-0.58) vs 4 (SD-0.76),
      (P<0.01), and instrument handling-1.84 (SD-0.61) vs 4.25 (SD-0.71), (P<0.01)
      (construct validity). The study also suggested test-retest and interrater
      reliability. CONCLUSIONS: This study suggests face, content, and constructs
      validity and reliability of the TEC as a training tool for TLN.

PMID- 25565551
TI  - Self-Monitoring and the Metatraits.
AB  - Prior attempts at locating self-monitoring within general taxonomies of
      personality traits have largely proved unsuccessful. However, past research has
      typically neglected (a) the bidimensionality of the Self-Monitoring Scale and (b)
      the hierarchical nature of personality. The objective of this study was to test
      hypotheses that the two self-monitoring factors are located at the level of the
      metatraits. Using data from two large multi-informant samples, one community
      (Sample 1: N = 552, Mage  = 51.26, 61% female; NPeers  = 1,551, Mage  = 48.61,
      37% female) and one online (Sample 2: N = 3,726, Mage  = 24.89, 59% female;
      NPeers  = 17,868, Mage  = 26.23, 64% female), confirmatory factor analysis was
      used to test the hypotheses. Results confirmed hypotheses that acquisitive self
      monitoring would have a strong positive relation to metatrait Plasticity, whereas
      protective self-monitoring would have a moderate negative relation to metatrait
      Stability. In both samples, constraining the correlation between acquisitive self
      monitoring and Plasticity to unity did not alter model fit indices, indicating
      that the two putatively distinct constructs are identical. Findings have wide
      ranging implications, including integration of the construct of self-monitoring
      into the mainstream of personality research, as the latter moves toward the
      development of broad explanatory theories.

PMID- 25565553
TI  - Quantifying flood risks in the Netherlands.
AB  - The Flood Risk in the Netherlands project (Dutch acronym: VNK2) is a large-scale
      probabilistic risk assessment for all major levee systems in the Netherlands.
      This article provides an overview of the methods and techniques used in the VNK2
      project. It also discusses two examples that illustrate the potential of
      quantitative flood risk assessments such as VNK2 to improve flood risk management
      processes: (i) informing political debates about the risks of flooding and the
      effectiveness of risk management actions, and (ii) (re)directing research efforts
      towards important sources of uncertainty. 

PMID- 25565552
TI  - The intergenerational effect of war.

PMID- 25565554
TI  - Ambient temperature sodium-sulfur batteries.
AB  - Ambient- or room-temperature sodium-sulfur batteries (RT Na-S) are gaining much
      attention as a low-cost option for large-scale electrical energy storage
      applications. However, their adoption is hampered by severe challenges. This
      concept paper summarizes first the operating principles, history, recent
      progress, and challenges of RT Na-S battery technology, and then suggests future
      directions towards enhancing performance in order for it to be a viable
      technology. 

PMID- 25565556
TI  - Functional material features of Bombyx mori silk light versus heavy chain
      proteins.
AB  - Bombyx mori (BM) silk fibroin is composed of two different subunits: heavy chain
      and light chain fibroin linked by a covalent disulfide bond. Current methods of
      separating the two silk fractions is complicated and produces inadequate
      quantities of the isolated components for the study of the individual light and
      heavy chain silks with respect to new materials. We report a simple method of
      separating silk fractions using formic acid. The formic acid treatment partially
      releases predominately the light chain fragment (soluble fraction) and then the
      soluble fraction and insoluble fractions can be converted into new materials. The
      regenerated original (total) silk fibroin and the separated fractions (soluble vs
      insoluble) had different molecular weights and showed distinctive pH stabilities
      against aggregation/precipitation based on particle charging. All silk fractions
      could be electrospun to give fiber mats with viscosity of the regenerated
      fractions being the controlling factor for successful electrospinning. The silk
      fractions could be mixed to give blends with different proportions of the two
      fractions to modify the diameter and uniformity of the electrospun fibers formed.
      The soluble fraction containing the light chain was able to modify the viscosity
      by thinning the insoluble fraction containing heavy chain fragments, perhaps
      analogous to its role in natural fiber formation where the light chain provides
      increased mobility and the heavy chain producing shear thickening effects. The
      simplicity of this new separation method should enable access to these different
      silk protein fractions and accelerate the identification of methods,
      modifications, and potential applications of these materials in biomedical and
      industrial applications. 

PMID- 25565557
TI  - Hypocrellin B in hepatocellular carcinoma cells: Subcellular localization and
      sonodynamic damage.
AB  - PURPOSE: To study subcellular localization of hypocrellin B in hepatocellular
      carcinoma cells, and hypocrellin B-mediated sonodynamic action-induced cell
      damage. MATERIALS AND METHODS: After incubation with 2.5 MUM of hypocrellin B,
      human hepatocellular carcinoma HepG2 cells were exposed to ultrasound waves for 8
      sec at an intensity of 0.46 W/cm(2). Clonogenic survival of HepG2 cells was
      measured using a colony forming assay and light microscope. Ultrastructural
      morphology was observed using transmission electron microscope (TEM) and
      mitochondrial membrane potential (MMP) was assessed using confocal laser scanning
      microcope (CLSM) after rhodamine 123 staining. Additionally, subcellular
      localization of hypocrellin B in HepG2 cells with organelle probe staining was
      also observed using CLSM. RESULTS: The colony forming units of HepG2 cells
      decreased substantially after sonodynamic treatment. The results of TEM showed
      microvilli disappearance, apoptotic body formation, swollen mitochondria with
      loss of cristae and mitochondrial myelin-like features (or membrane whorls).
      Collapse of MMP was found in the treated cells. Hypocrellin B was distributed in
      mitochondria and lysosomes as well as in endoplasmic reticulum and Golgi
      apparatus. CONCLUSIONS: The findings demonstrated that sonodynamic action of
      hypocrellin B induced mitochondrial damage, survival inhibition, and apoptosis of
      HepG2 cells. Additionally, other subcellular organelles such as endoplasmic
      reticulum, Golgi apparatus and lysosomes were also the targets of hypocrellin B
      mediated sonodynamic action as well as mitochondria.

PMID- 25565555
TI  - The Association Between BMI and QCT-Derived Proximal Hip Structure and Strength
      in Older Men: A Cross-Sectional Study.
AB  - Although higher body mass index (BMI) is associated with higher bone mineral
      density, recent evidence indicates that increased BMI may not be consistently
      associated with reduced hip fracture risk. Moreover, substantial proportions of
      hip fractures occur among overweight and obese men and women. The role of
      increased BMI and obesity on bone density, structure, and strength at the hip is
      not well understood. We conducted cross-sectional analyses between BMI and
      various density and structure measures derived from quantitative computed
      tomography (QCT)-scans of the proximal femur, in 3067 men (mean age: 73 y) from
      the Osteoporotic Fractures in Men Study (MrOS). Finite element (FE) analysis of
      hip QCT scans was performed for a subcohort of 672 men to provide a measure of
      femoral strength for a simulated sideways fall. The impact force was estimated
      using patient-specific weight and height information. Multivariable general
      linear models were used to examine the associations between BMI and hip QCT
      measures. The relationship of BMI with hip QCT measures was significantly
      different between men categorized as non-obese and obese (P for interaction <=
      0.014). For non-obese men (BMI < 30), increasing BMI was associated with higher
      integral, cortical and trabecular vBMD, integral volume, cross-sectional area,
      and percent cortical volume (all p < 0.001). For obese men (BMI >=30), increasing
      BMI was not associated with any of those parameters. In addition, compared to non
      obese men, obese men had a higher hip strength, but also a higher ratio of impact
      force to strength (P  < 0.0001), in theory increasing their risk of hip fracture
      despite their increased strength. These results provide a better understanding of
      hip fracture risk in obese men.

PMID- 25565558
TI  - Induction of chronic oxidative stress, chronic inflammation and aberrant patterns
      of DNA methylation in the liver of titanium-exposed CBA/CaJ mice.
AB  - PURPOSE: To investigate the biological effects of titanium ((48)Ti, one of the
      important heavy ions found in space) in the liver of exposed-mice. MATERIALS AND
      METHODS: We gave adult male CBA/CaJ mice a whole-body exposure to a total dose of
      0, 0.1, 0.25 or 0.5 Gy of (48)Ti ions. The liver was collected at 1 week, 1
      month, and 6 months post-irradiation (five mice per treatment-group at each
      harvest-time). Three biological endpoints were used for evaluating the effects of
      (48)Ti ions: Oxidative-stress, inflammatory responses, and DNA-methylation (5
      methylcytosine and 5-hydroxymethylcytosine). RESULTS: Our data clearly
      demonstrated dose-dependent increases in oxidative stress and inflammatory
      responses in the liver of exposed mice at all time-points (Analysis of Variance
      or ANOVA, p < 0.05). Significant dose-dependent increases in the levels of 5
      methylcytosine were detected at 1 week and 1 month (ANOVA, p < 0.05). At 6 months
      post-irradiation, a significant increase in the level of 5-methylcytosine was
      found only in 0.5-Gy-(48)Ti-ion-exposed mice. In contrast, dose-dependent
      decreases in 5-hydroxymethylcytosine levels were found in the liver of exposed
      mice (ANOVA, p < 0.05) at all time-points. CONCLUSIONS: Chronic oxidative-stress,
      chronic inflammation, and persistent aberrant DNA-methylation occurred in the
      liver of (48)Ti-exposed mice. Hence, exposure to (48)Ti ions in space may pose
      health risks.

PMID- 25565559
TI  - Effect of occupational EMF exposure from radar at two different frequency bands
      on plasma melatonin and serotonin levels.
AB  - OBJECTIVE: To delineate the effect of chronic electromagnetic field (EMF)
      exposure from radar on plasma melatonin and serotonin levels in occupationally
      exposed military personnel. SUBJECTS AND METHODS: A total of 166 male military
      personnel participated in the study out of which only 155 joined for blood draw.
      They were divided into three sets: Control group (n = 68), exposure group I (n =
      40) exposed to 8-12 GHz and exposure group II (n = 58) working with radar at 12.5
      18 GHz frequency. The three groups were further split into two groups according
      to their years of service (up to 10 years and > 10 years) in order to investigate
      the effect of years of exposure from radar. Melatonin and serotonin levels were
      estimated by enzyme immunoassay in fasting blood samples collected from 06:00
      07:00 h. EMF measurements were recorded at different locations using Satimo EME
      Guard 'Personal Exposure Meter' and Narda 'Broad Band Field Meter'. RESULTS: The
      group I exposed population registered a minor though not significant decrease in
      plasma melatonin concentration while the other group II exposed population
      registered statistically significant decline in melatonin concentration when
      compared with controls. Highly significant increase in plasma serotonin levels
      was found in exposure group II when compared to control whereas marginal non
      significant rise was also registered in exposure group I in comparison to
      control. Exposure in terms of length of service up to 10 years did not produce
      any significant effect in the indoleamine levels in both the exposure groups when
      they were compared with their respective control groups. Whereas, length of
      service greater than 10 years was observed to decrease and increase respectively
      the melatonin and serotonin concentration significantly in exposure group II but
      not in exposure group I. However, correlation test did not yield any significant
      association between years of service and melatonin or serotonin levels
      respectively in both the exposure sets I and II. No significant association was
      observed between melatonin and serotonin levels as well. CONCLUSION: The study
      showed the EMF ability to influence plasma melatonin and serotonin concentration
      in radar workers, significantly in 12.5-18 GHz range with service period greater
      than 10 years.

PMID- 25565561
TI  - One-pot synthesis of functionalized germanium nanocrystals from a single source
      precursor.
AB  - One-pot syntheses of surface functionalized germanium nanocrystals (GeNCs) based
      upon traditional hot injection and microwave-assisted heating of a Ge(II)
      dihydride single source precursor have been developed. The reported procedures
      offer in situ hydrogermylation-based covalent attachment of alkene/alkyne derived
      surface moieties that give access to hydrophobic or hydrophilic GeNCs.

PMID- 25565560
TI  - Efficacy of a basal bolus insulin protocol to treat prednisolone-induced
      hyperglycaemia in hospitalised patients.
AB  - BACKGROUND/AIM: Few studies have specifically investigated treatment of
      prednisolone-induced hyperglycaemia. AIM: To determine if a basal bolus insulin
      (BBI) protocol for inpatient hyperglycaemia is effective in patients prescribed
      acute prednisolone for an inflammatory disease. METHODS: In a cross-sectional
      study, 66 patients with type 2 diabetes admitted to a general medical ward and
      treated with BBI for up to 5 days were studied. Twenty-four patients were taking
      prednisolone >=10 mg/day to treat an acute inflammatory disease. The remaining 42
      patients were a control group. The primary outcome was mean daily blood glucose
      level. RESULTS: There were no significant differences in glycosylated haemoglobin
      (8.1 +/- 1.0 vs 8.1 +/- 1.6%, P = 0.88), age (77 +/- 11 vs 75 +/- 14 years, P =
      0.57), male sex (63 vs 60%, P = 0.81) or body mass index (30.0 +/- 5.3 vs 30.2 +/
      11.5 kg/m(2) , P = 0.90) between patients taking prednisolone and controls. Mean
      daily glucose concentration was higher in patients taking prednisolone than in
      controls (12.2 +/- 0.3 vs 10.0 +/- 0.1 mmol/L, P < 0.001). Blood glucose level
      was higher in patients on prednisolone at 1700 h (14.6 +/- 0.6 vs 10.3 +/- 0.3
      mmol/L, P < 0.001) and 2100 h (14.5 +/- 0.6 vs 10.5 +/- 0.3 mmol/L, P < 0.001),
      with no significant differences at 0700 h and 1200 h. These findings occurred
      despite patients taking prednisolone receiving a higher daily insulin dose than
      controls (0.67-0.70 vs 0.61-0.65 U/kg, P = 0.001) because of higher doses of
      ultra-rapid-acting insulin at 1200 h and 1700 h. CONCLUSIONS: Hospitalised
      patients taking prednisolone had substantial afternoon and evening hyperglycaemia
      despite receiving BBI via a protocol for inpatient hyperglycaemia. Specific
      insulin regimens for prednisolone-induced hyperglycaemia are needed that
      recommend more insulin during this time period.

PMID- 25565562
TI  - Sensitivity of patients with familial cerebral cavernous malformations to
      therapeutic radiation.
AB  - Familial cerebral cavernous malformations are autosomal dominant conditions that
      can result in significant morbidity. A two-hit mechanism is accepted as likely
      responsible for formation of these malformations. We present two patients with
      this disease who received therapeutic radiation and developed very high numbers
      of malformations within the radiation ports, supporting radiation as an
      accelerator of lesion formation and suggesting implications for risks of
      radiation in this disease. 

PMID- 25565563
TI  - On-line hemodiafiltration or high-flow continuous hemodiafiltration is one of the
      most effective artificial liver support devices for acute liver failure in Japan.

PMID- 25565565
TI  - Listeria monocytogenes has a functional chitinolytic system and an active lytic
      polysaccharide monooxygenase.
AB  - Chitinases and chitin-active lytic polysaccharide monooxygenases (LPMOs) are most
      commonly associated with chitin metabolism, but are also reported as virulence
      factors in pathogenic bacteria. Listeria monocytogenes, a well-known virulent
      bacterium, possesses two chitinases (ChiA and ChiB) and a multi-modular lytic
      polysaccharide monooxygenase (LmLPMO10). These enzymes have been related to
      virulence and their role in chitin metabolism is poorly understood. It is thus of
      interest to functionally characterize the individual enzymes in order to shed
      light on their roles in vivo. Our results demonstrate that L. monocytogenes has a
      fully functional chitinolytic system. Both chitinases show substrate degradation
      rates similar to those of the nonprocessive endo-chitinase SmChiC from Serratia
      marcescens. Compared to the S. marcescens LPMO chitin-binding protein CBP21,
      LmLPMO10 shows a similar rate but different product profiles depending on the
      substrate. In LPMO-chitinase synergy experiments, CBP21 is able to boost the
      activity of both ChiA and ChiB more than LmLPMO10. Product analysis of the
      synergy assays revealed that the chitinases were unable to efficiently hydrolyse
      the LPMO products (chitooligosaccharide aldonic acids) with a degree of
      polymerization below four (ChiA and SmChiC) or three (ChiB). Gene transcription
      and protein expression analysis showed that LmLPMO10 is neither highly
      transcribed, nor abundantly secreted during the growth of L. monocytogenes in a
      chitin-containing medium. The chitinases on the other hand are both abundantly
      secreted in the presence of chitin. Although LmLPMO10 is shown to promote chitin
      degradation in tandem with the chitinases in vitro, the secretome and
      transcription data question whether this is the primary role of LmLPMO10 in vivo.

PMID- 25565566
TI  - Mast cell activation is involved in stress-induced epithelial barrier dysfunction
      in the esophagus.
AB  - OBJECTIVE: We aimed to investigate the role of mast cell in stress-induced
      barrier dysfunction in the esophagus and its possible pathway involved using mast
      cell-deficient (Ws/Ws) rats. METHODS: Ws/Ws rats and normal (+/+) rats were
      submitted to chronic restraint stress (CRS) 2 h/day for 7 days. Tissues were
      obtained from distal esophagus. Mast cells were counted under Alcian blue
      safranin O stain. Activation of mast cells was assessed using transmission
      electron microscope. Esophageal epithelial barrier dysfunction was evaluated by
      measuring intercellular spaces (ICS) and by quantifying tight junction (TJ)
      proteins. The localization and expression of mast cell-derived tryptase and
      proteinase activated receptor 2 (PAR-2) were assessed. RESULTS: A higher number
      of mast cells and higher proportion of activated mast cells were observed in CRS
      +/+ rats compared with non-stress controls. Increased ICS and decreased
      expression of some TJ proteins were observed in the CRS +/+ rats but not in the
      CRS Ws/Ws rats. Tryptase and its receptor PAR-2 were found elevated concomitantly
      by nearly 100% in CRS +/+ rats, but not in CRS Ws/Ws rats. CONCLUSIONS: Mast
      cells play an important role in stress-induced epithelial barrier dysfunction in
      esophagus. The mechanism may involve the activation of PAR-2 by mast cell-derived
      tryptase, causing proinflammatory responses and the subsequent disruption of the
      epithelial TJ proteins and a disturbed cytoskeleton function, resulting in
      dilated intercellular spaces.

PMID- 25565567
TI  - Mortality in mothers after perinatal loss: a population-based follow-up study.
AB  - OBJECTIVE: To assess whether mothers who lost a child from stillbirth or in the
      first week of life have an increased overall mortality and cause-specific
      mortality. DESIGN: A population based follow-up study. SETTING: Data from Danish
      national registers. POPULATION: All mothers in Denmark were included in the
      cohort at time of their first delivery from 1 January 1980 to 31 December 2008
      and followed until 31 December 2009 or death, whichever came first. METHODS: The
      association between perinatal loss and total and cause-specific mortality in
      mothers was estimated with hazard ratios (HR) and 95% confidence intervals (95%
      CI) calculated using Cox proportional hazards regression analyses. MAIN OUTCOME
      MEASURES: Overall mortality and cause-specific mortality. RESULTS: During the
      follow-up period, 838,331 mothers in the cohort gave birth to one or more
      children and 7690 mothers (0.92%) experienced a perinatal loss. During follow-up,
      8883 mothers (1.06%) died. There was an increased overall mortality for mothers
      who experienced a perinatal loss adjusted for maternal age and educational level,
      hazard ratio (HR) 1.83 [95% confidence interval (CI) 1.55-2.17]. The strongest
      association was seen in mortality from cardiovascular diseases (CVD) with an HR
      of 2.29 (95% CI 1.48-3.52) adjusted for CVD at time of delivery. We found no
      association between a perinatal loss and mortality from traumatic causes.
      CONCLUSIONS: Mothers who experience a perinatal loss have an increased mortality,
      especially from CVD.

PMID- 25565569
TI  - Effect of harvest time on table grape quality during on-vine storage.
AB  - BACKGROUND: Postponing the harvest of grapes is a common practice in southern
      Italy, in order to delay harvest up to Christmas and make higher income from
      their sale. The aim of this work was to evaluate the effect of harvest time (over
      almost 3 months) on the quality of table grapes (cv. Italia). The experiment was
      repeated for two years (2010 and 2011). In 2010, grapes were harvested starting
      from 8 October and after 11, 27 and 48 days. In 2011, five harvest times were
      compared over a period of 56 days. Respiration rate, firmness, colour, sensory
      attributes, total soluble solids (TSS), pH, titratable acidity (TA), phenols and
      antioxidant activity were measured. In addition, in the second year, volatile
      compounds were evaluated. RESULTS: For both years, harvest time influenced most
      parameters, which indicated that metabolic changes took place in the plants. In
      2010, harvest time influenced respiration rate, cluster and berry appearance
      scores, colour attributes, crunchiness, pH, TA, total phenol content and
      antioxidant activity. In 2011, harvest time influenced respiration rate, colour
      attributes, most sensory attributes, TSS and TA. Generally, late harvested grapes
      showed higher firmness, berry appearance score, sweetness, fruity taste, overall
      sensory evaluation score and TSS. Regarding volatile compounds, terpene content
      decreased during ripening, while C6 compounds showed a nonlinear trend.
      CONCLUSION: The results showed that table grape sensory quality could be
      increased by delaying harvest up to a certain time of the season, while excessive
      delay could reduce final grape quality.

PMID- 25565570
TI  - Impact of serum glycosylated Wisteria floribunda agglutinin positive Mac-2
      binding protein levels on liver functional reserves and mortality in patients
      with liver cirrhosis.
AB  - AIM: Serum glycosylated Wisteria floribunda agglutinin positive Mac-2 binding
      protein (WFA(+) -M2BP) levels are a non-invasive and reliable marker to assess
      the degree of liver fibrosis. We investigated the use of WFA(+) -M2BP levels to
      predict mortality in patients with liver cirrhosis (LC). METHODS: This
      retrospective study consisted of 59 consecutive patients. Liver fibrosis was
      estimated by hyaluronic acid (HA), 7S fragment of type IV collagen (7S collagen),
      aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 index. The
      severity of liver disease was evaluated by Child-Pugh classification and the
      Model for End-Stage Liver Disease (MELD) score. Cox proportional hazards
      regression analysis was performed to evaluate risk factors for mortality, and the
      diagnostic accuracy of WFA(+) -M2BP levels to predict mortality was examined
      using receiver-operator curves. RESULTS: Serum WFA(+) -M2BP levels of Child-Pugh
      class A, B and C had cut-off indexes (COI) of 2.90, 6.15 and 9.45, respectively.
      WFA(+) -M2BP levels were positively correlated with HA, 7S collagen, APRI, FIB-4
      index, Child-Pugh class and MELD score. Multivariate analysis identified WFA(+) 
      M2BP levels as an independent risk factor of mortality (hazard ratio = 1.19, 95%
      confidence interval = 1.02-1.41, P = 0.03), and the optimal cutoff point to
      predict mortality was 5.0 COI. The survival rate was significantly lower in
      patients with WFA(+) -M2BP levels 5.0 or more COI than in patients with WFA(+) 
      M2BP of less than 5.0 COI (P = 0.002). CONCLUSION: Serum WFA(+) -M2BP levels were
      significantly correlated with both liver function reserves and liver fibrosis,
      and were independently associated with mortality in patients with LC.

PMID- 25565568
TI  - Intrapulmonary arteriovenous anastomoses in humans--response to exercise and the
      environment.
AB  - Intrapulmonary arteriovenous anastomoses (IPAVA) have been known to exist in
      human lungs for over 60 years. The majority of the work in this area has largely
      focused on characterizing the conditions in which IPAVA blood flow (QIPAVA ) is
      either increased, e.g. during exercise, acute normobaric hypoxia, and the
      intravenous infusion of catecholamines, or absent/decreased, e.g. at rest and in
      all conditions with alveolar hyperoxia (FIO2 = 1.0). Additionally, QIPAVA is
      present in utero and shortly after birth, but is reduced in older (>50 years)
      adults during exercise and with alveolar hypoxia, suggesting potential
      developmental origins and an effect of age. The physiological and
      pathophysiological roles of QIPAVA are only beginning to be understood and
      therefore these data remain controversial. Although evidence is accumulating in
      support of important roles in both health and disease, including associations
      with pulmonary arterial pressure, and adverse neurological sequelae, there is
      much work that remains to be done to fully understand the physiological and
      pathophysiological roles of IPAVA. The development of novel approaches to
      studying these pathways that can overcome the limitations of the currently
      employed techniques will greatly help to better quantify QIPAVA and identify the
      consequences of QIPAVA on physiological and pathophysiological processes.
      Nevertheless, based on currently published data, our proposed working model is
      that QIPAVA occurs due to passive recruitment under conditions of exercise and
      supine body posture, but can be further modified by active redistribution of
      pulmonary blood flow under hypoxic and hyperoxic conditions. 

PMID- 25565571
TI  - Unique model evokes the supination/pronation deficits found after Mason II
      fractures.
AB  - A rapid prototyping model of Mason II fracture was used to investigate baseline
      recommendations for surgical intervention founded on kinematic forearm rotational
      blockage. Exact replicas of the radial heads in nine cadaveric specimens were
      produced and specimens were tested in a physiologic elbow simulator. After
      testing supination/pronation, the rotations were repeated with native replicas
      and with replicas modeling 3 mm depressed Mason II fractures with and without a
      gap of 1 mm between the body and fragment. The fragments were located
      circumferentially around the radial head at 10, 2 and 6 o'clock positions. There
      was no statistical difference between the range of motion of the native case and
      the native replica without fracture. After inclusion of the fracture, seven of
      the nine specimens showed rotational blockages. A two-way ANOVA found no
      statistical difference due to type of Mason II fracture (p > 0.87) or fracture
      location (p > 0.27). A chi-square analysis showed that presence of a kinematic
      deficit with a fractured radial head was significant (p < 0.03). The results
      support continued surgical intervention for a 3 mm depressed fracture and also
      establish the use of the rapid prototype as a model for kinematic investigation
      of fractures in a cadaveric model when ligamentous attachments are preserved.

PMID- 25565573
TI  - Considerations and intervention in congenital muscular torticollis.
AB  - PURPOSE OF REVIEW: To present the current literature regarding congenital
      muscular torticollis (CMT) to promote the most effective and evidence-based
      intervention. CMT is a musculoskeletal deformity observed at birth or in infancy,
      characterized by persistent head tilt toward the ipsilateral side with the chin
      rotated toward the contralateral side. The incidence of torticollis is on the
      rise and as a result there has been a surge in the literature on the topic,
      however, until recently, there was little consensus on the treatment approach.
      RECENT FINDINGS: Research on CMT has gone in several directions. One branch is
      looking at diagnostics, imaging, and attempting to understand the underlying
      disease behind torticollis, down to the cellular level. This information may be
      helpful in the other, more clinical research vein to determine prognosis,
      establish plan of care, and create guidelines for the treatment of infants with
      torticollis. SUMMARY: CMT presents as a muscular imbalance. We know from the
      pediatric and adult literature, whether it is about cerebral palsy or anterior
      cruciate ligament reconstruction, that muscle imbalances can lead to skeletal
      changes, postural dysfunction, and impaired movement patterns. These can lead to
      functional limitations and limitations in participation. CMT, therefore, needs to
      be addressed. Although this article presents the current evidence and guidelines
      for treatment, there is still much to be learned regarding disease, optimal
      intervention, duration of treatment, and timing of follow-up. VIDEO ABSTRACT:
      http://links.lww.com/MOP/A24.

PMID- 25565574
TI  - The contribution of extended-spectrum beta-lactamases to multidrug-resistant
      infections in children.
AB  - PURPOSE OF REVIEW: The prevalence of multidrug-resistant (MDR) infections caused
      by Gram-negative rods (GNRs) such as Escherichia coli and Klebsiella pneumoniae
      is increasing in large part because of the production of extended-spectrum beta
      lactamases (ESBLs) that confer resistance to third-generation cephalosporins such
      as ceftriaxone. This review examines the clinical implication of changes in the
      epidemiology, diagnostic tools, and reporting criteria for ESBL-GNRs. RECENT
      FINDINGS: Pediatric ESBL-GNR infections, once associated only with hospitals, are
      increasing in the community. The most common risk factor for ESBL-GNR infection
      is previous antibiotic use. Evidence also exists for prolonged fecal carriage
      after discharge from neonatal ICUs, leading to community transmission with close
      contact of known carriers. Controversial changes in the laboratory criteria for
      GNR cephalosporin resistance have also contributed to the increased numbers of
      reported MDR-GNR infections. Newer diagnostic tools will enable more rapid
      identification of MDR-GNR infections, leading to earlier implementation of
      appropriate therapy. SUMMARY: ESBL-GNR infections are no longer limited to ICUs
      and are now being identified in children presenting from the community.
      Appropriate antibiotic prescribing practices are critical to limit the spread of
      ESBL-GNRs, and pediatricians must prepare to identify and treat these challenging
      infections.

PMID- 25565572
TI  - Advances in unrelated and alternative donor hematopoietic cell transplantation
      for nonmalignant disorders.
AB  - PURPOSE OF REVIEW: The role of hematopoietic cell transplantation in non
      malignant disorders has increased exponentially with the recognition that
      multiple diseases can be controlled or cured if engrafted with donor-derived
      cells. This review provides an overview of advances made in alternative donor
      transplants for nonmalignant disorders. RECENT FINDINGS: Stem cell sources, novel
      transplant methods, and sophisticated supportive care have simultaneously made
      giant strides toward improving the safety and efficacy of hematopoietic cell
      transplantation. This has led to the utilization of marrow, cord, peripheral
      blood stem cell and haploidentical stem cell sources, and novel reduced toxicity
      or reduced intensity conditioning regimens to transplant non-malignant disorders
      such as immune dysfunctions, marrow failure syndromes, metabolic disorders and
      hemoglobinopathies. Transplant complications such as graft rejection, infections,
      and graft versus host disease are better combated in this modern era of medicine,
      achieving better survival with decreased late effects. These aspects of
      transplant for non-malignant disorders are discussed. SUMMARY: This review
      presents the progress made in the realm of hematopoietic cell transplantation for
      non-malignant disorders. It advocates the consideration of alternative donor
      transplants in the absence of human leukocyte antigen matched siblings when
      indicated by disease severity. The ultimate goal is to provide curative
      transplant options for more patients that can benefit from this intervention,
      prior to detrimental outcomes.

PMID- 25565575
TI  - Visible-light-driven CO2 reduction with carbon nitride: enhancing the activity of
      ruthenium catalysts.
AB  - A heterogeneous photocatalyst system that consists of a ruthenium complex and
      carbon nitride (C3N4), which act as the catalytic and light-harvesting units,
      respectively, was developed for the reduction of CO2 into formic acid. Promoting
      the injection of electrons from C3N4 into the ruthenium unit as well as
      strengthening the electronic interactions between the two units enhanced its
      activity. The use of a suitable solvent further improved the performance,
      resulting in a turnover number of greater than 1000 and an apparent quantum yield
      of 5.7% at 400 nm. These are the best values that have been reported for
      heterogeneous photocatalysts for CO2 reduction under visible-light irradiation to
      date.

PMID- 25565578
TI  - Dawn of a new decade for JAMA Surgery.

PMID- 25565576
TI  - Genetically modified murine adipose-derived mesenchymal stem cells producing
      interleukin-2 favor B16F10 melanoma cell proliferation.
AB  - Adipose-derived mesenchymal stem cells (ADSCs) are attractive tools for cancer
      gene therapy due to their intrinsic tropism to the tumor environment. Interleukin
      2 (IL2) is recognized as a key regulatory molecule, which enhances the activity
      and growth of the immune effector cell function. High-Dose IL2 Therapy is an
      option for treatment of malignant melanoma but has frequent, often serious and
      sometimes life-threatening side effects. Here we investigated the effect of
      genetically modified ADSCs (GM-ADSCs) expressing IL2 in immunocompetent mouse
      models of subcutaneous and lung metastatic melanoma. Prior to in vivo studies, we
      demonstrated that IL2 produced by GM-ADSCs may act as a growth factor for
      melanoma cells due to the increased viability and reduced apoptosis of melanoma
      cells after in vitro treatment. Subcutaneous co-injection of IL2-expressing ADSCs
      with melanoma cells significantly enhanced the melanoma tumor growth.
      Furthermore, histological analysis of subcutaneous tumors for IL2 and Melan-A (a
      melanocytic differentiation marker) confirmed that most of cells in melanoma/IL2
      ADSC co-injected tumors are melanoma cells, not IL2-ADSCs. In pulmonary
      metastases model, melanoma cells were injected intravenously and 10 days later
      mice were treated by systematical injection of GM-ADSCs. Intravenously injected
      IL2-ADSCs engrafted into melanoma lung tumors but were unable to reduce melanoma
      lung metastases. Besides, administered IL2-ADSCs significantly reduced systemic
      CD4+ cells and did not impact the total survival of lung metastases melanoma
      bearing mice. In conclusion, this study showed that IL2-producing ADSCs can favor
      B16F10 melanoma cell proliferation. Therefore, therapies utilizing IL2 have to be
      taken into careful consideration. 

PMID- 25565577
TI  - How is national recipient hemovigilance conducted in the United States?
AB  - A national recipient hemovigilance system was introduced in the United States in
      2010, when voluntary enrollment began as part of the National Healthcare Safety
      Network (NHSN) Hemovigilance Module. NHSN is a secure, Web-based surveillance
      system operated by the Centers for Disease Control and Prevention and used by US
      health care facilities to report a variety of patient safety information. The
      Hemovigilance Module is used for comprehensive monitoring of transfusion-related
      adverse events. Participating facilities can utilize analytic tools available
      within the module to identify opportunities for enhancing transfusion safety,
      evaluate the effectiveness of interventions, and compare facility specific
      transfusion-related data to aggregate national estimates. Data may be voluntarily
      shared by facilities with external partners for patient safety improvement
      initiatives and to fulfill reporting mandates. We describe the key
      characteristics of the Hemovigilance Module, highlight the benefits for
      participating facilities, and discuss the use of reported data for establishing
      national estimates of transfusion-associated adverse events to identify gaps in
      transfusion safety and opportunities for interventions. National hemovigilance
      systems are essential to recognize gaps in transfusion safety and identify
      opportunities for interventions to improve patient safety and outcomes. 

PMID- 25565579
TI  - Coevolutionary dynamics of polyandry and sex-linked meiotic drive.
AB  - Segregation distorters located on sex chromosomes are predicted to sweep to
      fixation and cause extinction via a shortage of one sex, but in nature they are
      often found at low, stable frequencies. One potential resolution to this
      longstanding puzzle involves female multiple mating (polyandry). Because many
      meiotic drivers severely reduce the sperm competitive ability of their male
      carriers, females are predicted to evolve more frequent polyandry and thereby
      promote sperm competition when a meiotic driver invades. Consequently, the
      driving chromosome's relative fitness should decline, halting or reversing its
      spread. We used formal modeling to show that this initially appealing hypothesis
      cannot resolve the puzzle alone: other selective pressures (e.g., low fitness of
      drive homozygotes) are required to establish a stable meiotic drive polymorphism.
      However, polyandry and meiotic drive can strongly affect one another's frequency,
      and polyandrous populations may be resistant to the invasion of rare drive
      mutants. 

PMID- 25565580
TI  - Volume and porosity thermal regulation in lipid mesophases by coupling mobile
      ligands to soft membranes.
AB  - Short DNA linkers are increasingly being exploited for driving-specific self
      assembly of Brownian objects. DNA-functionalized colloids can assemble into
      ordered or amorphous materials with tailored morphology. Recently, the same
      approach has been applied to compliant units, including emulsion droplets and
      lipid vesicles. The liquid structure of these substrates introduces new degrees
      of freedom: the tethers can diffuse and rearrange, radically changing the physics
      of the interactions. Unlike droplets, vesicles are extremely deformable and DNA
      mediated adhesion causes significant shape adjustments. We investigate
      experimentally the thermal response of pairs and networks of DNA-tethered
      liposomes and observe two intriguing and possibly useful collective properties:
      negative thermal expansion and tuneable porosity of the liposome networks. A
      model providing a thorough understanding of this unexpected phenomenon is
      developed, explaining the emergent properties out of the interplay between the
      temperature-dependent deformability of the vesicles and the DNA-mediated adhesive
      forces. 

PMID- 25565582
TI  - Three-dimensional segmentation and reconstruction of the retinal vasculature from
      spectral-domain optical coherence tomography.
AB  - We reconstruct the three-dimensional shape and location of the retinal vascular
      network from commercial spectral-domain (SD) optical coherence tomography (OCT)
      data. The two-dimensional location of retinal vascular network on the eye fundus
      is obtained through support vector machines classification of properly defined
      fundus images from OCT data, taking advantage of the fact that on standard SD
      OCT, the incident light beam is absorbed by hemoglobin, creating a shadow on the
      OCT signal below each perfused vessel. The depth-wise location of the vessel is
      obtained as the beginning of the shadow. The classification of crossovers and
      bifurcations within the vascular network is also addressed. We illustrate the
      feasibility of the method in terms of vessel caliber estimation and the accuracy
      of bifurcations and crossovers classification.

PMID- 25565584
TI  - Comparison of an Online Mindfulness-based Cognitive Therapy Intervention With
      Online Pain Management Psychoeducation: A Randomized Controlled Study.
AB  - BACKGROUND: This study tested the effectiveness of a computerized mindfulness
      based cognitive therapy intervention compared with computerized pain management
      psychoeducation in a randomized study. METHODS: Using an intention-to-treat
      approach, 124 adult participants who reported experiencing pain that was
      unrelated to cancer and of at least 6 months duration were randomly assigned to
      computerized mindfulness-based cognitive therapy ("Mindfulness in Action" [MIA])
      or pain management psychoeducation programs. Data were collected before and after
      the intervention and at 6-month follow-up. RESULTS: Participants in both groups
      showed equivalent change and significant improvements on measures of pain
      interference, pain acceptance, and catastrophizing from pretreatment to
      posttreatment and the improvements were maintained at follow-up. Average pain
      intensity also reduced from baseline to posttreatment for both groups, but was
      not maintained at follow-up. Participants in both groups reported increases in
      subjective well-being, these were more pronounced in the MIA than the pain
      management psychoeducation group. Participants in the MIA group also reported a
      greater reduction in pain "right now," and increases in their ability to manage
      emotions, manage stress, and enjoy pleasant events on completion of the
      intervention. The changes in ability to manage emotions and stressful events were
      maintained at follow-up. CONCLUSIONS: The results of the study provide evidence
      that although there were equivalent changes across outcomes of interest for
      participants in both conditions over time, the MIA program showed a number of
      unique benefits. However, the level of participant attrition in the study
      highlighted a need for further attention to participant engagement with online
      chronic pain programs.

PMID- 25565581
TI  - The small GTPase Rab7 as a central regulator of hepatocellular lipophagy.
AB  - Autophagy is a central mechanism by which hepatocytes catabolize lipid droplets
      (LDs). Currently, the regulatory mechanisms that control this important process
      are poorly defined. The small guanosine triphosphatase (GTPase) Rab7 has been
      implicated in the late endocytic pathway and is known to associate with LDs,
      although its role in LD breakdown has not been tested. In this study, we
      demonstrate that Rab7 is indispensable for LD breakdown ("lipophagy") in
      hepatocytes subjected to nutrient deprivation. Importantly, Rab7 is dramatically
      activated in cells placed under nutrient stress; this activation is required for
      the trafficking of both multivesicular bodies and lysosomes to the LD surface
      during lipophagy, resulting in the formation of a lipophagic "synapse." Depletion
      of Rab7 leads to gross morphological changes of multivesicular bodies, lysosomes,
      and autophagosomes, consequently leading to attenuation of hepatocellular
      lipophagy. CONCLUSION: These findings provide additional support for the role of
      autophagy in hepatocellular LD catabolism while implicating the small GTPase Rab7
      as a key regulatory component of this essential process.

PMID- 25565583
TI  - Efficacy and Safety of Pregabalin in the Treatment of Patients With Painful
      Diabetic Peripheral Neuropathy and Pain on Walking.
AB  - OBJECTIVES: This randomized, double-blind, placebo-controlled, multicenter, 2
      period crossover study (two 6-week treatment periods separated by a 2-week
      washout period) evaluated the efficacy and safety of pregabalin (150 to 300 mg/d)
      for treatment of pain and pain on walking in patients with painful diabetic
      peripheral neuropathy (DPN) who experienced pain while walking. METHODS: Co
      primary efficacy endpoints were: (1) mean pain score (last 7 daily pain diary
      scores, 0 to 10 numeric rating scale at end of each treatment period) and (2) DPN
      pain on walking (0 to 10 numeric rating scale immediately after walking 50 feet
      [15.2 m] on flat surface). Secondary endpoints included other pain parameters,
      patient-reported sleep, health-related quality of life, and safety measures.
      RESULTS: Two hundred three patients were treated (pregabalin, n=198; placebo,
      n=186), with no statistically significant treatment difference for pregabalin
      versus placebo in the co-primary efficacy endpoints, mean DPN pain (P=0.0656) and
      mean DPN pain on walking (P=0.412). A carryover effect was observed. Analysis of
      co-primary endpoints for period 1 showed significant treatment difference for DPN
      pain (P=0.034) and DPN pain on walking (P=0.001). Treatment with pregabalin
      resulted in significant improvements versus placebo on prespecified patient
      global impression of change (end of period 1; P=0.002), and sleep interference
      rating scale (end of period 2; P=0.011). Adverse events were more frequent with
      pregabalin than with placebo and caused discontinuation in 13 (6.6%) pregabalin
      patients versus 5 (2.7%) placebo patients. DISCUSSION: Failure to meet the co
      primary objectives may be related to carryover effect from period 1 to period 2,
      lower pregabalin dose (150 to 300 mg/d), and/or placebo response in painful DPN.

PMID- 25565585
TI  - Development, Content Validity, and User Review of a Web-based Multidimensional
      Pain Diary for Adolescent and Young Adults With Sickle Cell Disease.
AB  - BACKGROUND: Vaso-occlusive pain, the hallmark of sickle cell disease (SCD), is a
      major contributor to morbidity, poor health-related quality of life, and health
      care utilization associated with this disease. There is wide variation in the
      burden, frequency, and severity of pain experienced by patients with SCD. As
      compared with health care utilization for pain, a daily pain diary captures the
      breadth of the pain experience and is a superior measure of pain burden and its
      impact on patients. Electronic pain diaries based on real-time data capture
      methods overcome methodological barriers and limitations of paper pain diaries,
      but their psychometric properties have not been formally established in patients
      with SCD. OBJECTIVES: To develop and establish the content validity of a web
      based multidimensional pain diary for adolescents and young adults with SCD and
      conduct an end-user review to refine the prototype. MATERIALS AND METHODS:
      Following identification of items, a conceptual model was developed. Interviews
      with adolescents and young adults with SCD were conducted. Subsequently, end-user
      review with use of the electronic pain diary prototype was conducted. RESULTS:
      Two iterative cycles of in-depth cognitive interviews in adolescents and young
      adults with SCD informed the design and guided the addition, removal, and
      modification of items in the multidimensional pain diary. Potential end-users
      provided positive feedback on the design and prototype of the electronic diary.
      CONCLUSION: A multidimensional web-based electronic pain diary for adolescents
      and young adults with SCD has been developed and content validity and initial end
      user reviews have been completed.

PMID- 25565586
TI  - The Incidence and Severity of Physical Pain Symptoms in Marfan Syndrome: A Survey
      of 993 Patients.
AB  - OBJECTIVE: To characterize the incidence, severity, quality, and treatment of
      pain in a large cohort of Marfan patients. MATERIALS AND METHODS: A web-based
      survey was distributed to all individuals on the Marfan Foundation listserv.
      Respondents who endorsed a diagnosis of Marfan syndrome were queried as to the
      presence, frequency, severity, location, and quality of their pain and were asked
      to describe the specific treatments used to manage pain. The primary outcome was
      the presence of pain symptoms in respondents during the 7-day period preceding
      completion of the survey. RESULTS: Of the 993 patients with a verified diagnosis
      of Marfan syndrome, 67% (95% confidence interval, 64%-69%) reported pain in the
      preceding 7 days. Median (interquartile range) "average daily pain" was 4 (3 to
      5) on the numeric rating scale; "worst pain" was 7 (5 to 8). "Worst pain
      experienced" was >=4 in 93% of respondents. Analgesic use to control pain related
      to Marfan syndrome was reported in 56% of respondents with 55% reporting <50%
      pain relief with this modality. Few patients underwent interventional procedures
      for pain control, despite intractable back and joint pain being common. A
      majority (52%) of respondents rated "chronic pain care" from their physicians as
      either "poor" or "fair." DISCUSSION: Our findings suggest that pain symptoms in
      Marfan patients are underestimated and likely undertreated. We propose a need for
      improved patient and medical provider awareness of pain management options in
      this population, including the development of effective algorithms to treat pain
      in Marfan patients.

PMID- 25565587
TI  - Piloting a Text Message-based Social Support Intervention for Patients With
      Chronic Pain: Establishing Feasibility and Preliminary Efficacy.
AB  - OBJECTIVES: To examine preliminarily the effectiveness of a short message service
      (SMS) text message-based social support intervention for reducing daily pain and
      pain interference levels, improving affect and perceptions of social support in
      patients with chronic noncancer pain, and exploring the feasibility of a novel
      mobile application to track perceptions of pain and pain interference. MATERIALS
      AND METHODS: Participants (17 men, 51 women) from 2 pain clinics in New York City
      downloaded a pain tracking application (App) on their Smartphone and used it to
      record twice-daily pain, pain interference, and affect scores over the 4-week
      study period. Participants were randomly assigned to receive standard care
      (control) or standard care along with receipt of twice-daily supportive SMS text
      messages delivered during the second and third week of the study (intervention).
      Demographic and clinical data were obtained at baseline, and social support
      measures were administered at baseline and at 4 weeks. Statistical analysis was
      carried out using general linear mixed models, taking into account variances
      associated with time of assessments and with patients. RESULTS: The social
      support intervention reduced perceptions of pain and pain interference and
      improved positive affect for chronic noncancer pain patients assigned to the
      intervention condition in comparison with controls. Participants completed
      approximately 80% of the daily measurements requested. DISCUSSION: These findings
      establish the feasibility of collecting daily pain data using a mobile tracking
      App and provide significant implications and insight into a nuanced approach to
      reducing the daily experience of pain through mobile technology, especially
      because of its accessibility.

PMID- 25565588
TI  - Which Factors Affect Daily Compliance With an Internet Headache Diary Among Youth
      With Migraine?
AB  - OBJECTIVE: To determine the specific factors that affect Internet headache diary
      compliance among youth with primary headaches. MATERIALS AND METHODS: Patients
      aged 10 to 18 years completed a 90-day Internet-based headache diary with date
      stamping and time-stamping features that allowed compliance monitoring. Eight
      potential predictors were assessed in a multilevel statistical model of headache
      diary compliance: age, sex, diary entries during the school year versus summer,
      entries on evenings preceding weekends (Friday or Saturday) versus evenings
      preceding weekdays (Sunday through Thursday), headache days versus nonheadache
      days, headache intensity ratings, use of an abortive headache medicine, and the
      first 2 weeks of diary use versus the latter 76 days. RESULTS: Fifty-two patients
      generated 4680 diary entries; 3215 (68.7%) entries were compliant (completed via
      same-day diary entries). Compliance for each diary participant ranged from 39% to
      97% (mean, 68.7%; median, 70%; SD=0.15%). Three specific factors were associated
      with diary compliance in the multilevel model. Compliance was better on days when
      an abortive headache medicine was used (P<0.001; odds ratio [OR], 33.7 [95%
      confidence interval [CI], 13.1-86.6]) and during the first 2 weeks of the diary
      period versus the remaining 76 days (P=0.05; OR, 1.3 [95% CI, 1.03-1.68]).
      Compliance was worse on evenings proceeding weekends versus evenings preceding
      weekdays (P<0.001; OR, 0.55 [95% CI, 0.46-0.66]). Patients who did not start the
      diary protocol (n=12) or did not complete the 90 days (n=14) were excluded from
      the analysis. DISCUSSION: Specific factors predict Internet-based headache diary
      compliance. Further research about the factors related to diary compliance and
      the optimization of diary-based data collection is warranted.

PMID- 25565589
TI  - Prevalence and Predictive Factors of Chronic Postsurgical Pain and Poor Global
      Recovery 1 Year After Outpatient Surgery.
AB  - OBJECTIVES: To prospectively describe the prevalence and predictive factors of
      chronic postsurgical pain (CPSP) and poor global recovery in a large outpatient
      population at a university hospital, 1 year after outpatient surgery. MATERIALS
      AND METHODS: A prospective longitudinal cohort study was performed. During 18
      months, patients presenting for preoperative assessment were invited to
      participate. Outcome parameters were measured by using questionnaires at 3
      timepoints: 1 week preoperatively, 4 days postoperatively, and 1 year
      postoperatively. A value of >3 on an 11-point numeric rating scale was considered
      to indicate moderate to severe pain. A score of <=80% on the Global Surgical
      Recovery Index was defined as poor global recovery. RESULTS: A total of 908
      patients were included. The prevalence of moderate to severe preoperative pain
      was 37.7%, acute postsurgical pain 26.7%, and CPSP 15.3%. Risk factors for the
      development of CPSP were surgical specialty, preoperative pain, preoperative
      analgesic use, acute postoperative pain, surgical fear, lack of optimism, and
      poor preoperative quality of life. The prevalence of poor global recovery was
      22.3%. Risk factors for poor global recovery were recurrent surgery because of
      the same pathology, preoperative pain, preoperative analgesic use, surgical fear,
      lack of optimism, poor preoperative and acute postoperative quality of life, and
      follow-up surgery during the first postoperative year. DISCUSSION: Moderate to
      severe CPSP after outpatient surgery is common, and should not be underestimated.
      Patients at risk for developing CPSP can be identified during the preoperative
      phase.

PMID- 25565591
TI  - Watch out for the wolves: predatory publishing.

PMID- 25565590
TI  - Postoperative radiotherapy is effective for thymic carcinoma but not for thymoma
      in stage II and III thymic epithelial tumors: the Japanese Association for
      Research on the Thymus Database Study.
AB  - BACKGROUND: The efficacy of postoperative radiotherapy (PORT) for thymic
      epithelial tumors is still controversial. Using the Japanese Association for
      Research on the Thymus (JART) database, this study was aimed at clarifying the
      efficacy of PORT for Masaoka stage II and III thymic carcinoma and thymoma.
      METHODS: The JART database registered the records of 2835 patients collected from
      32 Japanese institutions from 1991 to 2010. Thymic carcinoma and thymoma at stage
      II or III were extracted. The efficacy of PORT with respect to relapse-free
      survival (RFS) and overall survival (OS) was evaluated with the Kaplan-Meier
      method and Cox regression analysis. RESULTS: There were 1265 patients in all: 155
      thymic carcinoma cases (12.3%) and 1110 thymoma cases (87.7%). Eight hundred
      ninety-five (70.8%) were at stage II, and 370 (29.2%) were at stage III. Four
      hundred three cases (31.9%) underwent PORT. PORT for stage II and III thymic
      carcinoma was associated with increasing RFS (hazard ratio, 0.48; 95% confidence
      interval, 0.30-0.78; P = .003) but was not associated with OS (hazard ratio,
      0.94; 95% confidence interval, 0.51-1.75; P = .536). PORT for stage II and III
      thymoma was not associated with RFS or OS (P = .350). A subgroup analysis of
      stage III thymoma showed no factor associated with the efficacy of PORT.
      CONCLUSIONS: In this study, PORT did not increase RFS or OS for stage II or III
      thymoma but increased RFS for stage II and III thymic carcinoma.

PMID- 25565592
TI  - Young and midlife stroke survivors' experiences with the health services and long
      term follow-up needs.
AB  - The aim of this qualitative study was to explore young and midlife stroke
      survivors' experiences with the health services and to identify long-term follow
      up needs. Sixteen participants from two cohorts were interviewed in-depth. The
      interviews were analyzed applying a hermeneutic-phenomenological analysis. The
      participants struggled to gain access to follow-up health services. They felt
      that whether they were systematically followed up was more coincidental than
      planned. Young and midlife stroke survivors thus appear vulnerable to falling
      outside the follow-up system. Those participants who received some follow-up care
      perceived it as untailored to their specific needs. To be considered supportive,
      the follow-up programs must be in line with their long-term needs, take into
      account their particular challenges as young and midlife stroke survivors, and be
      planned in close collaboration with the individual patient. To secure systematic
      and follow-up health services tailored to the individual, knowledgeable and
      committed healthcare professionals should play a prominent role within the
      community health services. 

PMID- 25565593
TI  - Be wise: implementing a lifestyle intervention to reduce stroke risk in low
      income midlife women.
AB  - Stroke is a leading cause of death for women, and midlife, low-income women are
      unlikely to appreciate their risk for stroke. The Well-Integrated Screening and
      Evaluation for Women Across the Nation program, administered by the Centers for
      Disease Control and Prevention Division for Heart Disease and Stroke Prevention,
      was developed for this population. The program offers screenings, referrals, and
      evidence-based lifestyle interventions targeting poor nutrition and physical
      inactivity. The goal of "Be Wise," the evidence-based lifestyle intervention
      developed for the Illinois Well-Integrated Screening and Evaluation for Women
      Across the Nation program, is for midlife women to develop healthier diet and
      physical-activity-related behaviors and, as a result, reduce their risk for heart
      disease and stroke. The goal of this project was to implement "Be Wise" at a
      federally funded community health center serving a primarily Hispanic population.
      The project's director, a stroke program coordinator and clinical nurse
      specialist, for the area's advanced primary stroke center collaborated with the
      community health center's medical staff and registered dietitian in delivering
      the program. 

PMID- 25565594
TI  - Update of clinical practice guidelines for brain death determination in an
      academic heath center.
AB  - Brain death (BD) is determined after a patient has sustained some form of a
      catastrophic neurologic injury that results in an irreversible loss of cerebral
      and brain steam function. Variability is caused by the small number of patients
      who progress to BD annually causing a lack of opportunity for physicians and
      healthcare staff to stay competent in performing the examination. BACKGROUND: The
      current University of Cincinnati Medical Center policy on BD had not been updated
      since publication of the 2010 American Academy of Neurology guidelines on this
      subject. The diagnosis of BD in the medical community is an acceptable medical
      diagnosis, but the examination is difficult to perform, and explaining this
      diagnosis to a family can be challenging related to the emotions involved with
      discussing end of life. The goal of updating the current policy was to decrease
      variability in testing through consistency of practice among clinicians
      performing the examination. METHODS: An integrative review of the evidence-based
      literature was conducted to identify articles discussing both BD confirmation and
      secondary confirmatory testing. Using this integrative review, results from
      hospital-based chart reviews, and targeted provider surveys, a policy update was
      completed. The bedside medical clinicians were provided this policy with evidence
      based guidelines regarding performance of the clinical examination and
      confirmatory testing needed to diagnose BD and then communicate this diagnosis to
      the family. RESULTS: The current hospital policy lacked two important components
      of any BD policy: (a) the apnea test techniques and (b) guidance regarding
      secondary confirmatory testing. Both components were added during revision of the
      policy. Implementation of the new policy occurred through computer-based training
      that incorporated both didactic education of the updates and a video
      demonstration of a BD examination. DISCUSSION: A better defined policy for
      determining BD is essential. In addition, the implementation and quality
      assurance elements of the policy are necessary for efficiency and clinical
      decision making. By updating the policy within the University of Cincinnati
      Medical Center, the clinicians have been equipped with the latest evidence to
      perform the clinical examination for diagnosis of BD and then appropriately
      communicate this diagnosis to the family.

PMID- 25565595
TI  - Lemierre's syndrome.

PMID- 25565596
TI  - Barriers to oral fluid intake: beyond thickened liquids.
AB  - OBJECTIVES: Substandard oral fluid intake in poststroke patients receiving
      thickened liquids has been well documented; however, more recently, it has been
      reported in poststroke patients receiving thin liquids. Factors contributing to
      substandard fluid intake have been limited to the altered taste/texture of
      thickened beverages. The aim of this study was to determine if functional
      deficits poststroke based on admission Functional Independence Measure (FIM)
      scores for expression, problem solving, memory, and eating as well as dysphagia
      severity predict oral fluid intake for poststroke patients regardless of liquid
      viscosity. A second aim was to determine if there is a significant difference in
      the amount of oral fluids offered and consumed between patients receiving thin
      liquids and patients receiving thickened liquids. METHODS: Thirty-nine patients
      with a new diagnosis of ischemic stroke participated. Patients were assigned to
      one of two groups based on the consistency of liquids they were receiving: group
      1, 21 receiving thin liquids, and group 2, 18 receiving nectar or honey
      consistency. Fluids offered and consumed were monitored for 72 consecutive hours.
      Admission FIM scores and dysphagia severity ratings were collected. RESULTS:
      Functional deficits in eating significantly predicted oral fluid intake in the
      thin-liquid group (p = .0575), whereas functional deficits in cognition (memory
      and problem solving) significantly predicted oral fluid intake in the thickened
      liquid group (p = .0037). Patients receiving thin liquids consumed significantly
      more than patients receiving thickened liquids (mean = 1,405.45 ml and SD = +/
      727.1 ml vs. mean = 906.58 ml and SD = +/-317.4 ml; p = .0031); however, they
      were also offered significantly more fluids (mean = 2,574.7 ml vs. 1,588.9 ml, p
      = .0002). CONCLUSIONS: On average, poststroke patients consume substandard amount
      of fluid during hospitalization, regardless of viscosity. Although patients
      receiving thin liquids consumed significantly more, they were offered, on
      average, approximately 1,000 ml more fluids per 24-hour period than the thickened
      liquid group. Functional deficits after stroke influence oral fluid intake and
      should be considered as potential barriers to fluid intake for poststroke
      patients.

PMID- 25565598
TI  - Predictors of physical functioning in postoperative brain tumor patients.
AB  - A cross-sectional predictive design was used to study the relationships among
      recovery symptoms, mood state, and physical functioning and to identify
      predictors of physical functioning in patients who underwent surgery for brain
      tumor at the first follow-up visit (2 weeks) after hospital discharge. The sample
      included 88 patients who were 18 years or older, had full level of consciousness,
      and underwent first-time surgery for brain tumor without other adjuvant
      treatments from a tertiary hospital in Bangkok, Thailand. Descriptive statistics,
      Pearson product-moment correlation coefficient, and multiple regression were used
      for data analysis. The results revealed that most participants were women (75%)
      with an average age of 45.18 +/- 11.49 years, having benign brain tumors (91%)
      and pathological results as meningioma (48.9%). The most common recovery symptoms
      were pain (mean = 3.2, SD = 2.6) and sleep disturbance (mean = 3.1, SD = 3.0). As
      for mood state, the problem of confusion was found the most (mean = 4.6, SD =
      2.7). The physical functioning problem found the most was work aspect (mean =
      66.3, SD = 13.3). Recovery symptoms had positive relationships with physical
      functioning and mood state (r = .406, .716; p < .01), respectively. At the same
      time, mood state had positive relationships with physical functioning (r = .288,
      p < .01). Recovery symptoms, total mood disturbance, fatigue, and vigor were
      statistically significant predictors of physical functioning and could explain
      variance of postoperative physical functioning in these patients at 2 weeks after
      discharge by 35%. Total mood disturbance was the strongest predictor of physical
      functioning followed by vigor, fatigue, and recovery symptom, respectively.
      Interventions to improve physical functioning in postoperative brain tumor
      patients during home recovery should account for not only recovery symptom
      management but also mood state. 

PMID- 25565599
TI  - Testing a reality orientation program in patients with traumatic brain injury in
      a neurointensive care unit.
AB  - PRIMARY OBJECTIVE: The aim of this study was to examine the effect of a
      systematic reality orientation program (RO) introduced in a neurointensive care
      unit on duration of posttraumatic amnesia (PTA) and outcomes of patients with
      traumatic brain injury (TBI). RESEARCH DESIGN: This study used a
      quasiexperimental, prospective design. METHODS AND PROCEDURES: Twenty-four
      patients (intervention) with a significant TBI classified as moderate-to-severe
      injuries as measured by scores of less than 12 on the Glasgow Coma Scale
      underwent an RO program compared with a similar group of 38 patients (control)
      who received a conventional rehabilitation program. The Rancho Los Amigos Score
      was used to assess the cognitive level 24 hours after the end of sedation, and
      the Galveston Orientation and Amnesia Test was used daily to assess orientation
      and duration of PTA. The Glasgow Outcome Scale Extended was then used as an
      indicator of clinical outcome after 12 months. MAIN OUTCOMES AND RESULTS: The
      preliminary results indicated that patients who received the RO had a higher mean
      of the Glasgow Outcome Scale Extended (SD = 1.53) than those receiving the usual
      care (SD = 1.35) despite that the groups differed significantly (p = .01) in PTA
      duration. CONCLUSION: Patients with TBI may benefit from early assessment and
      systematic RO nursing intervention. The RO may facilitate patients with PTA to
      regain orientation and interact with their surroundings in the neurointensive
      care unit to optimize the recovery. However, further studies with focus on
      timing, intensity, and duration are needed to evaluate the influence of an early
      RO approach on PTA and outcomes in patients experiencing TBI.

PMID- 25565600
TI  - Staphylococcus aureus and primary lysis of eosinophils.

PMID- 25565601
TI  - GSK3beta negatively regulates LPS-induced osteopontin expression via inhibiting
      its transcription.
AB  - Osteopontin (OPN) is expressed by a variety of immune cells and is critical for
      both innate and adaptive immune responses. The expression status of OPN might be
      tightly regulated to maintain immune homeostasis. However, the mechanisms by
      which OPN is negatively regulated in LPS-stimulated macrophages remain largely
      unknown. In this study, we showed that glycogen synthase kinase 3beta (GSK3beta)
      inhibitors - SB216763, LiCl and azakenpaullone - enhanced LPS-induced OPN
      expression in mouse peritoneal macrophages. GSK3beta knock-down had the similar
      effects. Furthermore, we found that GSK3beta inhibitors and GSK3beta knock-down
      both increased the activity of OPN promoter in LPS-stimulated macrophages.
      GSK3beta inhibitor-mediated enhancement of LPS-induced OPN promoter activity was
      abrogated in GSK3beta siRNA-treated macrophages. Therefore, we identified
      GSK3beta as a negative regulator of OPN expression and suggest GSK3beta as a
      potential therapeutic target for the intervention of diseases with uncontrolled
      OPN production. 

PMID- 25565603
TI  - Platinum-induced kidney damage: Unraveling the DNA damage response (DDR) of renal
      tubular epithelial and glomerular endothelial cells following platinum injury.
AB  - BACKGROUND: Platinum compounds are potent anticancer drugs but also evoke
      considerable normal tissue damage. Here, we elucidate the molecular mechanisms
      contributing to the nephrotoxic effects of cisplatin. METHODS: We comparatively
      investigated the stress responses of rat kidney tubular (NRK-52E) and glomerular
      cells (RGE) following treatment with cisplatin (CisPt), oxaliplatin (OxaliPt) and
      carboplatin (CarboPt). To this end, cell viability, apoptosis, cell cycle
      progression, DNA damage response (DDR) and repair of DNA adducts were
      investigated. RESULTS: CisPt reduced the viability of tubular NRK-52E and
      glomerular RGE cells most efficiently. Cytotoxicity evoked by CarboPt occurred
      with a delay, which might be related to a retarded formation of Pt-(GpG)
      intrastrand crosslinks. RGE cells were more sensitive towards all platinum
      compounds than NRK-52E cells. Platinum drugs efficiently induced caspase-mediated
      apoptosis in tubular cells, while RGE cells favored G2/M arrest when treated with
      equitoxic platinum doses. Mitotic index of NKR-52E and RGE cells was worst
      affected by OxaliPt. Activation of the DDR was strikingly agent- and cell type
      specific. Most comprehensive and substantial stimulation of DDR mechanisms was
      provoked by CisPt. Repair of Pt-(GpG) intrastrand crosslinks was best in RGE,
      which was reflected by high mRNA expression of nucleotide excision repair (NER)
      factors. CONCLUSIONS: There are substantial differences regarding the cause of
      sensitivity and mechanisms of DDR between tubular and glomerular cells following
      platinum injury. CisPt is the most potent stimulator of the DDR. We hypothesize
      that specific DNA adducts and thereby forcefully activated pro-toxic DDR
      mechanisms contribute to the exceptionally high acute nephrotoxicity of CisPt.

PMID- 25565604
TI  - Role Breadth Self-Efficacy and Foci of Proactive Behavior: Moderating Role of
      Collective, Relational, and Individual Self-Concept.
AB  - This study aims to identify the interactive effect of role breadth self-efficacy
      (RBSE) and the three levels of self-concept (collective, relational, and
      individual) in predicting of different foci of proactive behaviors. Results from
      259 matched responses from an airline company in Taiwan showed that RBSE had a
      positive effect on (1) pro-organizational proactive behavior among those with
      higher collective self-concept, (2) pro-supervisor proactive behavior among those
      with higher relational self-concept, and (3) pro-self proactive behavior among
      those with higher individual self-concept. Our findings provide insights into the
      moderating role of different levels of self-concept on RBSE-proactive behavior
      process in terms of specific targets or beneficiaries. Further implications for
      organizational research and practice are discussed. 

PMID- 25565602
TI  - In vivo clonal overexpression of neuroligin 3 and neuroligin 2 in neurons of the
      rat cerebral cortex: Differential effects on GABAergic synapses and neuronal
      migration.
AB  - We studied the effect of clonal overexpression of neuroligin 3 (NL3) or
      neuroligin 2 (NL2) in the adult rat cerebral cortex following in utero
      electroporation (IUEP) at embryonic stage E14. Overexpression of NL3 leads to a
      large increase in vesicular gamma-aminobutyric acid (GABA) transporter (vGAT) and
      glutamic acid decarboxylase (GAD)65 in the GABAergic contacts that the
      overexpressing neurons receive. Overexpression of NL2 produced a similar effect
      but to a lesser extent. In contrast, overexpression of NL3 or NL2 after IUEP does
      not affect vesicular glutamate transporter 1 (vGlut1) in the glutamatergic
      contacts that the NL3 or NL2-overexpressing neurons receive. The NL3 or NL2
      overexpressing neurons do not show increased innervation by parvalbumin
      containing GABAergic terminals or increased parvalbumin in the same terminals
      that show increased vGAT. These results indicate that the observed increase in
      vGAT and GAD65 is not due to increased GABAergic innervation but to increased
      expression of vGAT and GAD65 in the GABAergic contacts that NL3 or NL2
      overexpressing neurons receive. The majority of bright vGAT puncta contacting the
      NL3-overexpressing neurons have no gephyrin juxtaposed to them, indicating that
      many of these contacts are nonsynaptic. This contrasts with the majority of the
      NL2-overexpressing neurons, which show plenty of synaptic gephyrin clusters
      juxtaposed to vGAT. Besides having an effect on GABAergic contacts,
      overexpression of NL3 interferes with the neuronal radial migration, in the
      cerebral cortex, of the neurons overexpressing NL3.

PMID- 25565606
TI  - A reference model based interface terminology for generic observations in
      Anatomic Pathology Structured Reports.
AB  - BACKGROUND: Current terminology systems for structured reporting in pathology are
      more or less focused on tumor pathology. They have not been compiled in a
      systematic approach, therefore they gather terms of very different granularity.
      Generic models for terminology development could help in establishing reference
      terminologies for all fields of anatomic pathology. METHODS: For each element
      template of PathLex its possible generic nature and its value set was analyzed,
      looking for the uniqueness or multiplicity of the values in the value sets.
      RESULTS: The 488 PathLex element templates for Anatomic Pathology (AP)
      observations can be reduced to 53 generic templates, leaving out only 17
      templates very specific for organ and/or disease. Among those 53 templates 28 are
      describing UICC-TNM staging, ICD-O-classification, and grading. Further 15
      templates describe the results from marker investigations. Almost all of the
      terms, used in those templates could be mapped to SNOMED CT. All of the generic
      elements have their "organ specific" counterparts by assigning them to one of 20
      organs and invasive or noninvasive cancer, respectively. Studying the structure
      of generic and specific terms it becomes obvious that any AP observation: -
      occurs always in a context; - consists of three basic elements (target of
      observation, property of observation, additional qualifiers, added by value sets
      for coded data). CONCLUSIONS: If a machine-readable terminology is aimed to
      preserve all the information of native speaking, then two principal solutions
      exist: - ystematic consideration of all the aspects mentioned above in each
      single term; - ocusing on the generic elements of terms and combining this with
      the structure of communication, reflecting the non-obvious elements of the
      terminology. The fastest way for establishing an interface terminology is the
      first approach, which lists all of the terms needed for e.g. a checklist in a
      comprehensive manner (precoordination).

PMID- 25565605
TI  - Dynamic Mitochondrial Localisation of STAT3 in the Cellular Adipogenesis Model
      3T3-L1.
AB  - A mechanistic relationship exists between protein localisation, activity and
      cellular differentiation. Understanding the contribution of these molecular
      mechanisms is required for elucidation of conditions that drive development.
      Literature suggests non-canonical translocation of the Signal Transducer and
      Activator of Transcription 3 (STAT3) to the mitochondria contributes to the
      regulation of the electron transport chain, cellular respiration and reactive
      oxygen species production. Based on this we investigated the role of
      mitochondrial STAT3, specifically the serine 727 phosphorylated form, in cellular
      differentiation using the well-defined mouse adipogenic model 3T3-L1. Relative
      levels of reactive oxygen species (ROS) and the levels and dynamic localization
      of pSTAT3S727 were investigated during the initiation of adipogenesis. As a
      signalling entity, ROS is known to regulate the activation of C/EBPbeta to
      stimulate a critical cascade of events prior to differentiation of 3T3-L1.
      Results indicate that upon induction of the differentiation programme, relative
      levels of mitochondrial pSTAT3S727 dramatically decrease in the mitochondria; in
      contrast the total cellular pSTAT3S727 levels increase. A positive correlation
      between increasing levels of ROS and dynamic changes in C/EBPbeta indicate that
      mitochondrial STAT3 plays a potential critical role as an initiator of the
      process. Based on these findings we propose a model for mitochondrial STAT3 as a
      regulator of ROS in adipogenesis.

PMID- 25565607
TI  - Test-retest reliability of pain extent and pain location using a novel method for
      pain drawing analysis.
AB  - BACKGROUND: Pain drawings (PDs) are an important component of the assessment of a
      patient with pain. The aim of this work is to present the test-retest reliability
      of a novel method of quantifying the extent and location of pain. Additionally,
      the association between PD variables and clinical features in patients with
      chronic neck pain (CNP) and chronic low back pain (CLBP) was explored. METHODS:
      Fifty-one patients with CLBP and 56 patients with CNP participated. Each patient
      shaded two consecutive PDs using a digital tablet. Software was developed to
      quantify the pain extent, to analyse the pain overlap between PDs and to produce
      pain frequency maps. Correlations were obtained between pain extent and clinical
      features including the level of pain intensity, disability, and psychological
      distress and cognitive function. RESULTS: The intraclass correlation coefficients
      for pain extent in CLBP and CNP were very high: 0.97 (95% CI: 0.95-0.98) and 0.92
      (95% CI: 0.87-0.98), respectively. The Bland Altman showed a mean difference
      close to zero: 5.4% pixels in CNP group and 3% pixels in the CLBP group.
      Significant correlations were observed between pain extent and pain intensity in
      CLBP and CNP and pain extent and disability in CNP. There was no relation between
      pain extent and the level of distress or cognitive function. CONCLUSIONS: A novel
      method for the acquisition of PD was presented. Test-retest reliability of
      reporting pain extent and pain location was supported in people with CNP and
      CLBP. Future research is needed to establish psychometric properties of PD.

PMID- 25565608
TI  - The "medical-industrial complex".

PMID- 25565609
TI  - Commercial pressures on professionalism in american medical care: from Medicare
      to the Affordable Care Act.
AB  - Since the passage of Medicare, the self-regulation characteristic of
      professionalism in health care has come under steady assault. While Canadian
      physicians chose to relinquish financial autonomy, they have enjoyed far greater
      professional autonomy over their medical judgments than their U.S. counterparts
      who increasingly have their practices micromanaged. The Affordable Care Act
      illustrates the ways that managerial strategies and a market model of health care
      have shaped the financing and delivery of health care in the U.S., often with
      little or no evidence of their effectiveness. 

PMID- 25565610
TI  - When worlds collide: medicine, business, the Affordable Care Act and the future
      of health care in the U.S.
AB  - The dialogue about the future of health care in the US has been impeded by flawed
      conceptions about medicine and business. The present paper re-examines some of
      the underlying assumptions about both medicine and business, and uses more
      nuanced readings of both terms to frame debates about the ACA and the emerging
      health care environment. 

PMID- 25565611
TI  - Between liberal aspirations and market forces: Obamacare's precarious balancing
      act.
AB  - The 2010 Affordable Care Act (ACA) represents a milestone in U.S. health care
      policy. The ACA moves the American health care system away, in important
      respects, from market-driven health care, including imposing new regulations on
      health insurers. Yet the ACA also relies, in other respects, on market forces to
      achieve its aims, including its embrace of health plan competition and high
      deductible insurance. This article explores how the ACA balances liberal
      aspirations and market principles, and the implications for health reform
      implementation and the future of U.S. health care. 

PMID- 25565612
TI  - Selling hospice.
AB  - Americans are increasingly turning to hospice services to provide them with
      medical care, pain management, and emotional support at the end of life. The
      increase in the rates of hospice utilization is explained by a number of factors
      including a "hospice movement" dating to the 1970s which emphasized hospice as a
      tool to promote dignity for the terminally ill; coverage of hospice services by
      Medicare beginning in 1983; and, the market for hospice services provision,
      sustained almost entirely by governmental reimbursement. On the one hand, the
      growing acceptance of hospice may be seen as a sign of trends giving substance to
      the death-with-dignity movement and the growing strength of end-of-life decision
      makers and planners who integrate medical, community, family and spiritual
      networks. On the other hand, the precise relationship between the death-with
      dignity and commercial processes driving hospice utilization rates are not well
      understood. On May 2, 2013, the U.S. Government intervened in a lawsuit brought
      by former hospice employees alleging that behind Vitas Innovative Hospice Care,
      the largest for-profit hospice service provider in the United States, lie an
      intricate web of incentives for patient intake nurses, physicians and marketers
      which not only drove hospice patients to use more expensive (and medically
      unnecessary) crisis care services, but influenced patient and family decisions as
      to whether or not to discontinue curative treatment. The corporate, investment,
      and regulatory history behind Vitas provides an important insight into the market
      realities behind Americans' embrace of hospice care and the risks to patient
      autonomy and health that accompany the commercialization of this ethically and
      morally complex health care service. 

PMID- 25565613
TI  - Beyond the market: the role of constitutions in health care system convergence in
      the United States of America and the United Kingdom.
AB  - Health care reform in the United States (US) and United Kingdom (UK) has resulted
      in the cross-fertilization of policy. The "new" health care models adopted by the
      two jurisdictions utilize free market principles for reasons of quality,
      efficiency, and cost, but also feature characteristics of a state-run model,
      through the provision of a safety net for citizens and a buffer against the
      commodification of health. In this sense, the health care systems of the US and
      UK are more congruent than they were. Here we identify two distinct narratives
      that emerge from health care reform undertaken in these jurisdictions. The
      "revolutionary" narrative views the reforms as fundamental change whilst the
      "evolutionary" narrative accepts them as natural development. We argue that
      neither the revolutionary nor the evolutionary narrative adequately characterizes
      the reforms undertaken in health care because neither takes sufficient account of
      the broader setting in which reform has occurred. In seeking to examine and
      explain the jurisdictions' apparent drive to the middle, we propose a distinctive
      evolutionary narrative, that of "convergence," which, as well as adopting a less
      parochial perspective on developments in health care policy and provision, also
      situates the reforms politically, constitutionally, and comparatively. 

PMID- 25565615
TI  - Curing the disobedient patient: medication adherence programs as pharmaceutical
      marketing tools.
AB  - Pharmaceutical companies have long focused their marketing strategies on getting
      doctors to write more prescriptions. But they lose billions in potential sales
      when patients do not take their prescribed drugs. Getting patients to "adhere" to
      drug therapies that have unpleasant side effects and questionable efficacy
      requires more than mere ad campaigns urging patients to talk to their doctors. It
      requires changing patients' beliefs and attitudes about their medications through
      repeated contact from people patients trust. Since patients do not trust drug
      companies, these companies are delivering their marketing messages through
      nurses, pharmacists, and even other patients--leveraging patients' trust in these
      intermediaries to persuade them to consume more brand name drugs. Armed with the
      premise that better adherence improves patients' health, drug companies justify
      manipulating patients by reframing reasonable decisions to decline therapy as
      pathological, and promote brand loyalty in the guise of offering medical care.

PMID- 25565614
TI  - Trust and transparency: patient perceptions of physicians' financial
      relationships with pharmaceutical companies.
AB  - Financial ties between physicians and pharmaceutical companies are pervasive and
      controversial. However, little is known about how patients perceive such ties.
      This paper describes an experiment examining how a national sample of U.S. adults
      perceived a variety of financial relationships between physicians and drug
      companies. Each respondent read a single scenario about a hypothetical physician
      and his financial ties to the pharmaceutical industry; scenarios varied in terms
      of payment type of (e.g., payment for meals vs. consulting fees) and amount.
      Respondents then evaluated the physician on several dimensions (e.g., expertise,
      trustworthiness, knowledge of new treatments, moral character, focus on patients'
      interests). Findings revealed that perceptions of the physician were more
      strongly influenced by payment type than by payment amount. Specifically,
      respondents were quite critical of doctors who owned drug company stock or
      received industry payments for meals and lodging, but were more forgiving of
      physicians who received free drug samples (which were perceived as benefiting
      patients) or consulting fees (which were seen as signaling physician expertise).
      Interestingly, physicians who received no payments, while seen as honest, were
      also viewed by some respondents as inexperienced or uninformed about new
      treatments. Implications for public policy and future research are discussed. 

PMID- 25565616
TI  - Economism and the commercialization of health care.
AB  - Those concerned over the excessive commercialization of health care, to the
      detriment of both professional and patient-centered values, commonly propose
      remedies that assume that meaningful change can occur largely within the health
      care sector. I argue instead that a major shift in the public culture and
      political discourse of the U.S. will be required if the commercialization of
      health care is to be adequately addressed. The notion that health and health care
      are commodities to be bought and sold in the market is encouraged by the ideology
      that is preferably called economism, though also today labeled neoliberalism,
      market fundamentalism, market triumphalism, and other terms. This ideology has
      been successful in pushing aside alternative accounts and policies over the past
      four decades, so that economism-inspired policies seem both commonsensical and
      inevitable. This dominance of the public political discourse hides two important
      facts about economism - it is a quasi-religious ideology that pretends to be a
      reflection of economic science; and it is shot through with internal
      contradictions that ultimately render it self-defeating as a guide to policy.
      Advocates for reduced commercialism in health care must directly address
      economism and attempt to educate the public and policymakers about its flaws. 

PMID- 25565617
TI  - The hair stylist, the corn merchant, and the doctor: ambiguously altruistic.
AB  - The medical profession has a tradition of presenting itself as exceptionally
      altruistic. This article challenges the idea that physicians are, or should be,
      more altruistic than other professionals or other people, and goes so far as to
      posit that even a professional aspiration of altruism can have negative
      consequences. 

PMID- 25565618
TI  - Medical versus fiscal gatekeeping: navigating professional contingencies at the
      pharmacy counter.
AB  - This paper theorizes that care provision depends on the set of "contingencies,"
      or organizational and institutional structures, rules, narratives, and routines,
      surrounding professional work. Drawing on 95 interviews with U.S. pharmacists, I
      demonstrate how pharmacists prioritize specific contingencies and reveal how
      ethical decision-making depends on both organizational positioning and locus in
      inter-professional hierarchies. 

PMID- 25565620
TI  - All together now: developing a team skills competency domain for global health
      education.
AB  - Global health is by definition and necessity a collaborative field; one that
      requires diverse professionals to address the clinical, biological, social, and
      political factors that contribute to the health of communities, regions, and
      nations. While much work has been done in recent years to define the field of
      global health and set forth discipline-specific global health competencies, less
      has been done in the area of interprofessional global health education. This
      paper documents the results of a roundtable that was convened to study the need
      for an interprofessional team skills competency domain for global health
      students. The paper sets forth a preliminary set of team competencies based on
      existing scholarship and the results of the roundtable. Once an agreed upon set
      of competencies is defined, a valuable next task will be development of a model
      curriculum to teach team skills to students in global health. The preliminary
      competencies offered in this paper represent a good first step toward ensuring
      that global health professionals are able to collaborate effectively to make the
      field as cohesive and collaborative as the mighty task of global health demands. 

PMID- 25565619
TI  - Upstream health law.
AB  - For the first time, entrepreneurs are aggressively developing new technologies
      and business models designed to improve individual and population health, not
      just to deliver specialized medical care. Consumers of these goods and services
      are not yet "patients"; they are simply people. As this sector of the health care
      industry expands, it is likely to require new forms of legal governance, which we
      term "upstream health law." 

PMID- 25565621
TI  - Medical innovation then and now: perspectives of innovators responsible for
      transformative drugs.
AB  - Effective medical innovation is a common goal of policymakers, physicians,
      researchers, and patients both in the private and public sectors. With the recent
      slowdown in approval of new transformative prescription drugs, many have looked
      back to the "golden years" of the 1980s and 1990s when numerous breakthrough
      products emerged. We conducted a qualitative study of innovators (n=127) directly
      involved in creation of groundbreaking drugs during that era to determine what
      made their work successful and how the process of conducting medical innovation
      has changed over the past 3 decades. Transcripts were analyzed using standard
      coding techniques and the constant comparative method of qualitative data
      analysis to identify the positive features of and challenges posed by the past
      and present therapeutic innovation environments (70 of the 127 interviewees
      explicitly addressed these issues). Interviewees emphasized the continued central
      role played by individuals and the institutions they were a part of in driving
      innovation. In addition, respondents discussed the importance of collaboration
      between individuals and institutions to share resources and expertise. Strong
      underlying basic science was also cited to be a major contributing factor to the
      success of an innovation. The climate for modern-day medical innovation involves
      a greater emphasis on patenting in academia, difficulty negotiating the
      technology transfer process, and funding constraints. Regulatory demands or
      reimbursement concerns were not commonly cited as factors that influenced
      transformative innovation. This study suggests that generating future
      transformative innovation will require a simplification of the current technology
      transfer process, continued commitment to basic science research, and policy
      changes that promote meaningful collaboration between individuals from disparate
      institutions. 

PMID- 25565623
TI  - Autonomy and paternalism in health policy: currents in contemporary bioethics.

PMID- 25565622
TI  - The fiduciary relationship model for managing clinical genomic "incidental"
      findings.
AB  - This paper examines how the application of legal fiduciary principles (e.g.,
      physicians' duty of loyalty and care, duty to inform, and duty act within the
      scope of authority), can serve as a framework to promote management of clinical
      genomic "incidental" or secondary target findings that is patient-centered and
      consistent with recognized patient autonomy rights. The application of fiduciary
      principles to the clinical genomic testing context gives rise to at least four
      physician fiduciary duties in conflict with recent recommendations by the
      American College of Medical Genetics and Genomics (ACMG). These recommendations
      have generated much debate among lawyers, clinicians, and bioethicists hence I
      believe this publication will be of value and interest to your readership. 

PMID- 25565624
TI  - Global emergency legal responses to the 2014 Ebola outbreak: public health and
      the law.

PMID- 25565626
TI  - Interpretation of aged sorption studies for pesticides and their use in European
      Union regulatory leaching assessments.
AB  - First-tier regulatory exposure assessments for pesticides assume that pesticide
      sorption is instantaneous and fully reversible. In European Union (EU) regulatory
      guidance, an increase in sorption over time ("aged sorption") can be considered
      at the higher tier to refine predicted environmental concentrations in
      groundwater. Research commissioned by the UK Chemicals Regulation Directorate
      (CRD), funded by the Department for Environment Food & Rural Affairs (Defra),
      formed the basis of a draft regulatory guidance document proposing 1) a protocol
      on how to measure aged sorption of parent compounds in laboratory studies, 2)
      procedures to fit kinetic models to the experimental data, 3) criteria to test
      the reliability of the parameters, and 4) procedures for use of the parameters in
      the groundwater exposure assessment. The draft guidance was revised after
      feedback from stakeholders and testing of the guidance was performed against real
      data sets by an independent consultancy. The Chemicals Regulation Directorate
      submitted the revised document to the European Food Safety Authority (EFSA) for
      scrutiny. This article gives an overview of the draft guidance and explains the
      reasoning behind the recommendations made.

PMID- 25565627
TI  - Dance/movement therapy for improving psychological and physical outcomes in
      cancer patients.
AB  - BACKGROUND: Current cancer care increasingly incorporates psychosocial
      interventions. Cancer patients use dance/movement therapy to learn to accept and
      reconnect with their bodies, build new self-confidence, enhance self-expression,
      address feelings of isolation, depression, anger and fear and to strengthen
      personal resources. OBJECTIVES: To update the previously published review that
      examined the effects of dance/movement therapy and standard care versus standard
      care alone or standard care and other interventions on psychological and physical
      outcomes in patients with cancer. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue
      6), MEDLINE (OvidSP, 1950 to June week 4, 2014), EMBASE (OvidSP, 1980 to 2014
      week 26), CINAHL (EBSCOhost, 1982 to July 15 2014), PsycINFO (EBSCOhost, 1806 to
      July 15 2014), LILACS (Virual Health Library, 1982 to July 15 2014), Science
      Citation Index (ISI, 1974 to July 15 2014), CancerLit (1983 to 2003),
      International Bibliography of Theatre and Dance (1989 to July 15 2014), the
      National Research Register (2000 to September 2007), Proquest Digital
      Dissertations, ClinicalTrials.gov, and Current Controlled Trials (all to July 15
      2014). We handsearched dance/movement therapy and related topics journals,
      reviewed reference lists and contacted experts. There was no language
      restriction. SELECTION CRITERIA: We included all randomized and quasi-randomized
      controlled trials of dance/movement therapy interventions for improving
      psychological and physical outcomes in patients with cancer. We considered
      studies only if dance/movement therapy was provided by a formally trained
      dance/movement therapist or by trainees in a formal dance/movement therapy
      program. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted
      the data and assessed the methodological quality, seeking additional information
      from the trial researchers when necessary. Results were presented using
      standardized mean differences. MAIN RESULTS: We identified one new trial for
      inclusion in this update. In total, the evidence for this review rests on three
      studies with a total of 207 participants.We found no evidence for an effect of
      dance/movement therapy on depression (standardized mean difference (SMD) = 0.02,
      95% confidence interval (CI) -0.28 to 0.32, P = 0.89, I2 = 0%) (two studies, N =
      170), stress (SMD = -0.18, 95% CI -0.48 to 0.12, P = 0.24, I2 = 0%) (two studies,
      N = 170), anxiety (SMD = 0.21, 95% CI -0.09 to 0.51 P = 0.18, I2 = 0%) (two
      studies, N = 170), fatigue (SMD = -0.36, 95% -1.26 to 0.55, P = 0.44, I2 = 80%)
      (two studies, N = 170) and body image (SMD = -0.13, 95% CI -0.61 to 0.34, P =
      0.58, I2 = 0%) (two studies, N = 68) in women with breast cancer. The data of one
      study with moderate risk of bias suggested that dance/movement therapy had a
      large beneficial effect on 37 participants' quality of life (QoL) (SMD = 0.89,
      95% CI 0.21 to 1.57). One study with a high risk of bias reported greater
      improvements in vigor and greater reduction in somatization in the dance/movement
      therapy group compared to a standard care control group (N = 31). The individual
      studies did not find support for an effect of dance/movement therapy on mood,
      mental health, and pain. It is unclear whether this was due to ineffectiveness of
      the treatment, inappropriate outcome measures or limited power of the trials.
      Finally, the results of one study did not find evidence for an effect of
      dance/movement therapy on shoulder range of motion (ROM) or arm circumference in
      37 women who underwent a lumpectomy or breast surgery. However, this was likely
      due to large within-group variability for shoulder ROM and a limited number of
      participants with lymphedema.Two studies presented moderate risk of bias and one
      study high risk of bias. Therefore, overall, the quality of the evidence is very
      low. AUTHORS' CONCLUSIONS: We did not find support for an effect of
      dance/movement therapy on depression, stress, anxiety, fatigue and body image .
      The findings of individual studies suggest that dance/movement therapy may have a
      beneficial effect on QoL, somatization, and vigor. However, the limited number of
      studies prevents us from drawing conclusions concerning the effects of
      dance/movement therapy on psychological and physical outcomes in cancer patients.

PMID- 25565628
TI  - Sputum induction improves detection of pathogens in children with cystic
      fibrosis.
AB  - BACKGROUND: Sputum induction is a safe, well tolerated means of obtaining lower
      airway secretions from children with cystic fibrosis (CF), particularly for
      assessment of airway inflammation but the clinical value in diagnosing outpatient
      infections has not been extensively studied. OBJECTIVES: Investigate the success
      rate and microbiologic yield of induced sputum (IS) compared to oropharyngeal
      swabs (OP) and expectorated sputum (ES) samples in children with CF, and
      determine if IS culture results impact treatment. METHODS: Two cohorts were
      included in this prospective, longitudinal comparative study. In one cohort,
      simultaneously collected OP, ES, and IS specimens were obtained from 17 CF
      children at three visits over 1 year. In the second group, sputum induction was
      performed in 35 CF subjects at four annual visits, and culture results were
      compared to their nearest respiratory culture within 4 months. Antimicrobial
      treatment regimens were captured retrospectively. RESULTS: Sputum induction was
      successful in 149 of 158 (94%) visit encounters. Polymicrobial infection
      (combined P = 0.005) and gram negative organisms (combined P = 0.003) were
      detected more frequently in IS samples compared to OP, as were the individual
      pathogens Pseudomonas aeruginosa (combined P = 0.04) and Stenotrophomonas
      maltophilia (combined P = 0.05). The microbiologic yield of serial IS samples
      collected over 1 year was stable. IS culture results led to antibiotic changes in
      6% of visit encounters. However, based on current practice 13% of visits could
      have resulted in treatment changes. CONCLUSIONS: Sputum induction is feasible in
      the outpatient setting and appears to improve pathogen detection in children with
      CF.

PMID- 25565629
TI  - Pharmacological inhibition of Polo-like kinase 1 (PLK1) by BI-2536 decreases the
      viability and survival of hamartin and tuberin deficient cells via induction of
      apoptosis and attenuation of autophagy.
AB  - The mechanistic target of rapamycin complex 1 (mTORC1) increases translation,
      cell size and angiogenesis, and inhibits autophagy. mTORC1 is negatively
      regulated by hamartin and tuberin, the protein products of the tumor suppressors
      TSC1 and TSC2 that are mutated in Tuberous Sclerosis Complex (TSC) and sporadic
      Lymphangioleiomyomatosis (LAM). Hamartin interacts with the centrosomal and
      mitotic kinase polo-like kinase 1 (PLK1). Hamartin and tuberin deficient cells
      have abnormalities in centrosome duplication, mitotic progression, and
      cytokinesis, suggesting that the hamartin/tuberin heterodimer and mTORC1
      signaling are involved in centrosome biology and mitosis. Here we report that
      PLK1 protein levels are increased in hamartin and tuberin deficient cells and LAM
      patient-derived specimens, and that this increase is rapamycin-sensitive.
      Pharmacological inhibition of PLK1 by the small-molecule inhibitor BI-2536
      significantly decreased the viability and clonogenic survival of hamartin and
      tuberin deficient cells, which was associated with increased apoptosis. BI-2536
      increased p62, LC3B-I and GFP-LC3 punctae, and inhibited HBSS-induced degradation
      of p62, suggesting that PLK1 inhibition attenuates autophagy. Finally, PLK1
      inhibition repressed the expression and protein levels of key autophagy genes and
      proteins and the protein levels of Bcl(-)2 family members, suggesting that PLK1
      regulates both autophagic and apoptotic responses. Taken together, our data point
      toward a previously unrecognized role of PLK1 on the survival of cells with
      mTORC1 hyperactivation, and the potential use of PLK1 inhibitors as novel
      therapeutics for tumors with dysregulated mTORC1 signaling, including TSC and
      LAM. 

PMID- 25565630
TI  - Sensitive and multiplexed on-chip microRNA profiling in oil-isolated hydrogel
      chambers.
AB  - Although microRNAs (miRNAs) have been shown to be excellent indicators of disease
      state, current profiling platforms are insufficient for clinical translation.
      Here, we demonstrate a versatile hydrogel-based microfluidic approach and novel
      amplification scheme for entirely on-chip, sensitive, and highly specific miRNA
      detection without the risk of sequence bias. A simulation-driven approach is used
      to engineer the hydrogel geometry and the gel-reaction environment is chemically
      optimized for robust detection performance. The assay provides 22.6 fM
      sensitivity over a three log range, demonstrates multiplexing across at least
      four targets, and requires just 10.3 ng of total RNA input in a 2 hour and 15
      minutes assay. 

PMID- 25565631
TI  - Combinations of bacterial species associated with symptomatic endodontic
      infections in a Chinese population.
AB  - AIM: To use microarrays to detect 11 selected bacteria in infected root canals,
      revealing bacterial combinations that are associated with clinical symptoms and
      signs of primary endodontic infections in a Chinese population. METHODOLOGY: DNA
      was extracted from 90 samples collected from the root canals of teeth with
      primary endodontic infections in a Chinese population, and the 16S rRNA gene was
      amplified by polymerase chain reaction (PCR). The PCR products were hybridized to
      microarrays containing specific oligonucleotide probes targeting 11 species, and
      the arrays were screened with a confocal laser scanner. Pearson's chi-squared
      test and cluster analysis were performed to investigate the associations between
      the bacterial combinations and clinical symptoms and signs using SAS 8.02.
      RESULTS: Seventy-seven samples (86%) yielded at least one of the 11 target
      species. Parvimonas micra (56%), Porphyromonas endodontalis (51%), Tannerella
      forsythia (48%), Prevotella intermedia (44%) and Porphyromonas gingivalis (37%)
      were the most prevalent taxa and were often concomitant. The following positive
      associations were found between the bacterial combinations and clinical features:
      P. endodontalis and T. forsythia with abscess; P. gingivalis and P. micra with
      sinus tract; P. gingivalis and P. endodontalis or P. micra and P. endodontalis
      with abscess and sinus tract; and the combination of P. endodontalis, P. micra,
      T. forsythia and P. gingivalis with sinus tract (P < 0.05). CONCLUSIONS: Various
      combinations of P. micra, P. endodontalis, T. forsythia and P. gingivalis may
      contribute to abscesses or sinus tracts of endodontic origin with bacterial
      synergism in a Chinese population.

PMID- 25565632
TI  - The cylindromatosis gene product, CYLD, interacts with MIB2 to regulate notch
      signalling.
AB  - CYLD, an ubiquitin hydrolase, has an expanding repertoire of regulatory roles in
      cell signalling and is dysregulated in a number of cancers. To dissect CYLD
      function we used a proteomics approach to identify CYLD interacting proteins and
      identified MIB2, an ubiquitin ligase enzyme involved in Notch signalling, as a
      protein which interacts with CYLD. Coexpression of CYLD and MIB2 resulted in
      stabilisation of MIB2 protein levels and was associated with reduced levels of
      JAG2, a ligand implicated in Notch signalling. Conversely, gene silencing of CYLD
      using siRNA, resulted in increased JAG2 expression and upregulation of Notch
      signalling. We investigated Notch pathway activity in skin tumours from patients
      with germline mutations in CYLD and found that JAG2 protein levels and Notch
      target genes were upregulated. In particular, RUNX1 was overexpressed in CYLD
      defective tumour cells. Finally, primary cell cultures of CYLD defective tumours
      demonstrated reduced viability when exposed to gamma-secretase inhibitors that
      pharmacologically target Notch signalling. Taken together these data indicate an
      oncogenic dependency on Notch signalling and suggest potential novel therapeutic
      approaches for patients with CYLD defective tumours. 

PMID- 25565633
TI  - A bovine cell line that can be infected by natural sheep scrapie prions.
AB  - Cell culture systems represent a crucial part in basic prion research; yet, cell
      lines that are susceptible to prions, especially to field isolated prions that
      were not adapted to rodents, are very rare. The purpose of this study was to
      identify and characterize a cell line that was susceptible to ruminant-derived
      prions and to establish a stable prion infection within it. Based on species and
      tissue of origin as well as PrP expression rate, we pre-selected a total of 33
      cell lines that were then challenged with natural and with mouse propagated BSE
      or scrapie inocula. Here, we report the successful infection of a non-transgenic
      bovine cell line, a sub-line of the bovine kidney cell line MDBK, with natural
      sheep scrapie prions. This cell line retained the scrapie infection for more than
      200 passages. Selective cloning resulted in cell populations with increased
      accumulation of PrPres, although this treatment was not mandatory for retaining
      the infection. The infection remained stable, even under suboptimal culture
      conditions. The resulting infectivity of the cells was confirmed by mouse
      bioassay (Tgbov mice, Tgshp mice). We believe that PES cells used together with
      other prion permissive cell lines will prove a valuable tool for ongoing efforts
      to understand and defeat prions and prion diseases. 

PMID- 25565635
TI  - Chromosomal instability but lack of transformation in human myoblast
      preparations.
AB  - Genetic alterations have recently been described as emerging during the culture
      of embryonic stem cells or induced pluripotent stem cells, raising concerns about
      their safety in future clinical use. Myoblasts are adult stem cells with
      important therapeutic potential that have been used in clinical trials for almost
      20 years, but their genome integrity has not yet been established. Here we
      produced 10 human myoblast preparations and investigated their genomic stability.
      At the third passage, half of the preparations had a normal karyotype and half
      showed one to four alterations/30 metaphases. Chromosome 2 trisomy was found in 1
      2/30 metaphases and/or 2/100 nuclei by FISH in 3/10 samples, and there was no
      other recurrent anomaly. When prolonging cultures, these erratic abnormalities
      were never associated with a growth advantage. Cellular senescence was manifested
      in all samples by growth arrest before passage 15. Expression of TERT was always
      negative. Molecular analysis of individual p53 transcripts did not reveal
      tumorigenic mutations. CGH array (10 samples) and exome sequencing (one sample)
      failed to detect copy number variations or accumulation of mutations,
      respectively. Myoblasts did not grow either in soft agar or in vivo after
      injection in immunodeficient mice. Hence, occasional genomic abnormalities may
      occur during myoblast culture but are not associated with risk of transformation.

PMID- 25565634
TI  - Life-threatening hemorrhaging in neonatal ulcerated congenital hemangioma: two
      case reports.
AB  - IMPORTANCE: Congenital hemangiomas (CHs) are rare benign vascular tumors that
      differ from common infantile hemangiomas in that they grow in utero and are fully
      developed at birth. While ulceration is a common, predominantly benign
      complication in infantile hemangioma, little is known about the prognosis of
      ulcerated CH. However, it has been observed that ulcerated CH may be complicated
      by life-threatening bleeding episodes. OBSERVATIONS: We report 2 cases of
      ulcerated rapidly involuting congenital hemangiomas (RICH) that were complicated
      by life-threatening bleeding episodes in the neonatal period. In both cases, the
      CHs were fed by high-flow vessels and the ensuing massive bleeding was due to
      superficial vessel wall erosion induced by the ulceration. Both patients were
      successfully treated with intravascular embolization; one patient underwent
      additional hemostatic surgery. CONCLUSIONS AND RELEVANCE: These 2 cases highlight
      the importance of closely monitoring children with ulcerated CH because of the
      risk of severe bleeding. Embolization is the treatment of choice in the case of
      severe bleeding, as the natural history of RICH is to spontaneously regress.

PMID- 25565636
TI  - Repeated administrations of human umbilical cord blood cells improve disease
      outcomes in a mouse model of Sanfilippo syndrome type III B.
AB  - Sanfilippo syndrome type III B (MPS III B) is an inherited disorder characterized
      by a deficiency of alpha-N-acetylglucosaminidase (Naglu) enzyme leading to
      accumulation of heparan sulfate in lysosomes and severe neurological deficits. We
      have previously shown that a single administration of human umbilical cord
      mononuclear cells (hUCB MNCs) into Naglu knockout mice decreased behavioral
      abnormalities and tissue pathology. In this study, we tested whether repeated
      doses of hUCB MNCs would be more beneficial than a single dose of cells. Naglu
      mice at 3 months of age were randomly assigned to either a Media-only group or
      one of three hUCB MNC treatment groups--single low dose (3 * 10(6) cells), single
      high dose (1.8 * 10(7) cells), or multiple doses (3 * 10(6) cells monthly for 6
      months) delivered intravenously; cyclosporine was injected intraperitoneally to
      immune suppress the mice for the duration of the study. An additional control
      group of wild-type mice was also used. We measured anxiety in an open field test
      and cognition in an active avoidance test prior to treatment and then at monthly
      intervals for 6 months. hUCB MNCs restored normal anxiety-like behavior in these
      mice (p < 0.001). The repeated cell administrations also restored hippocampal
      cytoarchitecture, protected the dendritic tree, decreased GM3 ganglioside
      accumulation, and decreased microglial activation, particularly in the
      hippocampus and cortex. These data suggest that the neuroprotective effect of
      hUCB MNCs can be enhanced by repeated cell administrations.

PMID- 25565637
TI  - Vasopressin decreases pulmonary-to-systemic vascular resistance ratio in a
      porcine model of severe hemorrhagic shock.
AB  - Vasopressors are gaining renewed interest as treatment adjuncts in hemorrhagic
      shock. The ideal vasoconstrictor will increase systemic blood pressure without
      increasing pulmonary vascular resistance (PVR), which hinders pulmonary perfusion
      and exacerbates hypoxemia. However, the selectivity of pressors for pulmonary
      versus systemic vasoconstriction during hemorrhage has not been characterized.
      The purpose of this study was to test the hypothesis that vasopressin (VP) has
      distinct effects on pulmonary versus systemic hemodynamics, unlike the
      catecholamine vasopressors norepinephrine (NE) and phenylephrine (PE).
      Anesthetized and ventilated pigs were assigned to resuscitation with saline only
      (n = 7) or saline with VP (n = 6), NE (n = 6), or PE (n = 6). Animals were
      hemorrhaged to a target volume of 30 mL/kg and a mean arterial pressure of 35
      mmHg. One hour after the start of hemorrhage, animals were resuscitated with
      saline up to one shed blood volume, followed by either additional saline or a
      vasopressor. Hemodynamics and oxygenation were measured hourly for 4 h after the
      start of hemorrhage. Vasopressin increased systemic vascular resistance (SVR)
      while sparing the pulmonary vasculature, leading to a 45% decrease in the PVR/SVR
      ratio compared with treatment with PE. Conversely, NE induced pulmonary
      hypertension and led to an increased PVR/SVR ratio associated with decreased
      oxygen saturation. Phenylephrine and crystalloid had no significant effect on the
      PVR/SVR ratio. Sparing of pulmonary vasoconstriction occurs only with VP, not
      with administration of crystalloid or catecholamine pressors. The ability of VP
      to maintain blood oxygenation indicates that VP may prevent hypoxemia in the
      management of hemorrhagic shock. 

PMID- 25565638
TI  - Refinement of animal models of sepsis and septic shock.
AB  - This report aims to facilitate the implementation of the Three Rs (replacement,
      reduction, and refinement) in the use of animal models or procedures involving
      sepsis and septic shock, an area where there is the potential of high levels of
      suffering for animals. The emphasis is on refinement because this has the
      greatest potential for immediate implementation. Specific welfare issues are
      identified and discussed, and practical measures are proposed to reduce animal
      use and suffering as well as reducing experimental variability and increasing
      translatability. The report is based on discussions and submissions from a
      nonregulatory expert working group consisting of veterinarians, animal
      technologists, and scientists with expert knowledge relevant to the field. 

PMID- 25565639
TI  - The hydrocortisone protection of glycocalyx on the intestinal capillary
      endothelium during severe acute pancreatitis.
AB  - Malfunctioning of the intestinal microcirculation secondary to severe acute
      pancreatitis (SAP) can cause injuries to the intestinal mucosal barrier,
      translocation of gut flora, and sepsis. The glycocalyx on the vascular
      endothelium helps maintain its normal function through multiple mechanisms,
      including regulation of vascular permeability and inhibition of intercellular
      adhesion. It is unknown that whether pancreatitis inflicts injuries to the
      intestinal mucosal barrier through damaging glycocalyx or stabilizing glycocalyx
      can be a potential therapeutic target in maintaining the integrity of the
      intestinal mucosal barrier during SAP. Injecting sodium taurocholate into the
      pancreatic duct of Sprague-Dawley rats induced SAP. Intestinal perfusion, changes
      in endothelial glycocalyx, and the associated molecular mechanisms were assessed
      by laser Doppler velocimetry, electron microscopy, and the levels of heparan
      sulfate, syndacan-1, and tumor necrosis factor-alpha (TNF-alpha) in the superior
      mesenteric vein. Protective effects of hydrocortisone treatment in the intestinal
      microcirculation during SAP were evaluated. Degradation of the glycocalyx in
      intestinal vascular endothelium developed 3 h after the onset of SAP in rats. By
      12 h, significant reduction of intestinal perfusion was observed. The concomitant
      elevated levels of TNF-alpha in the superior mesenteric vein suggest that TNF
      alpha is involved in the degradation of the glycocalyx. With the use of
      hydrocortisone, intestinal perfusion was improved and the degradation of
      glycocalyx was reduced. The degradation of glycocalyx is involved in the
      malfunction of the intestinal microcirculation. The massive release of TNF-alpha
      participates in this process and leads to glycocalyx degradation. Hydrocortisone
      may be a good therapy to prevent this process. 

PMID- 25565641
TI  - Preinjury Fed State Alters the Physiologic Response in a Porcine Model of
      Hemorrhagic Shock and Polytrauma.
AB  - INTRODUCTION: Hemorrhagic shock and injury lead to dramatic changes in metabolic
      demands and continue to be a leading cause of death. We hypothesized that
      altering the preinjury metabolic state with a carbohydrate load prior to injury
      would affect subsequent metabolic responses to injury and lead to improved
      survival. METHODS: Sixty-four pigs were randomized to fasted (F) or carbohydrate
      prefeeding (CPF) groups and fasted 12 h prior to experiment. The CPF pigs
      received an oral carbohydrate load 1 h prior to anesthesia. All pigs underwent a
      standardized injury/hemorrhagic shock protocol. Physiologic parameters and
      laboratory values were obtained at set time points. RESULTS: Carbohydrate
      prefeeding did not convey a survival benefit; instead, CPF animals had greater
      mortality rates (47% vs. 28%; P = 0.153; log-rank [Mantel-Cox]). Carbohydrate
      prefeeding animals also had higher rates of acute lung injury (odds ratio, 4.23;
      95% confidence interval, 1.1-16.3) and altered oxygen utilization. Prior to shock
      and throughout resuscitation, CPF animals had significantly higher serum glucose
      levels than did the F animals. CONCLUSIONS: Carbohydrate prefeeding did not
      provide a survival benefit to swine subjected to hemorrhagic shock and
      polytrauma. Carbohydrate prefeeding led to significantly different metabolic
      profile than in fasted animals, and prefeeding led to a greater incidence of lung
      injury, increased multiorgan dysfunction, and altered oxygen utilization.

PMID- 25565640
TI  - Individual-Specific, Beat-to-beat Trending of Significant Human Blood Loss: The
      Compensatory Reserve.
AB  - Current monitoring technologies are unable to detect early, compensatory changes
      that are associated with significant blood loss. We previously introduced a novel
      algorithm to calculate the Compensatory Reserve Index (CRI) based on the analysis
      of arterial waveform features obtained from photoplethysmogram recordings. In the
      present study, we hypothesized that the CRI would provide greater sensitivity and
      specificity to detect blood loss compared with traditional vital signs and other
      hemodynamic measures. Continuous noninvasive vital sign waveform data, including
      CRI, photoplethysmogram, heart rate, blood pressures, SpO2, cardiac output, and
      stroke volume, were analyzed from 20 subjects before, during, and after an
      average controlled voluntary hemorrhage of ~1.2 L of blood. Compensatory Reserve
      Index decreased by 33% in a linear fashion across progressive blood volume loss,
      with no clinically significant alterations in vital signs. The receiver operating
      characteristic area under the curve for the CRI was 0.90, with a sensitivity of
      0.80 and specificity of 0.76. In comparison, blood pressures, heart rate, SpO2,
      cardiac output, and stroke volume had significantly lower receiver operating
      characteristic area under the curve values and specificities for detecting the
      same volume of blood loss. Consistent with our hypothesis, CRI detected blood
      loss and restoration with significantly greater specificity than did other
      traditional physiologic measures. Single measurement of CRI may enable more
      accurate triage, whereas CRI monitoring may allow for earlier detection of
      casualty deterioration. 

PMID- 25565642
TI  - An Evolving Uncontrolled Hemorrhage Model Using Cynomolgus Macaques.
AB  - BACKGROUND: Trauma-induced hemorrhagic shock produces hemodynamic changes that
      often result in a systemic inflammatory response that can lead to multiple organ
      failure and death. In this prospective study, the pathophysiology of a nonhuman
      primate uncontrolled hemorrhagic shock model is evaluated with the goal of
      creating an acute systemic inflammatory syndrome response and a reproducible
      hemorrhage. METHODS: Nonhuman primates were divided into 2 groups. A laparoscopic
      left hepatectomy was performed in groups A and B, 60% and 80%, respectively,
      resulting in uncontrolled hemorrhage. Resuscitation during the prehospital phase
      lasted 120 min and included a 0.9% saline bolus at 20 mL/kg. The hospital phase
      involved active warming, laparotomy, hepatorrhaphy for hemostasis, and
      transfusion of packed red blood cells (10 mL/kg). The animals were recovered and
      observed over a 14-day survival period with subsequent necropsy for
      histopathology. RESULTS: Baseline demographics and clinical parameters of the two
      groups were similar. Group A (n = 7) underwent a 57.7% +/- 2.4% left hepatectomy
      with a 33.9% +/- 4.0% blood loss and 57% survival. Group B (n = 4) underwent an
      80.0% +/- 6.0% left hepatectomy with 56.0% +/- 3.2% blood loss and 75% survival.
      Group B had significantly lower hematocrit (P < 0.05) for all postinjury time
      points. Group A had significantly elevated creatinine on postoperative day 1.
      Nonsurvivors succumbed to an early death, averaging 36 h from the injury.
      Histopathologic evaluation of nonsurvivors demonstrated kidney tubular
      degeneration. CONCLUSIONS: Nonhuman primates displayed the expected physiologic
      response to hemorrhagic shock due to liver trauma as well as systemic
      inflammatory response syndrome with resultant multiple organ dysfunction syndrome
      and either early death or subsequent recovery. Our next step is to establish a
      clinically applicable nonhuman primate polytrauma model, which reproduces the
      prolonged maladaptive immunologic reactivity and end-organ dysfunction consistent
      with multiple organ failure found in the critically injured patient.

PMID- 25565643
TI  - Inflammation-induced increases in plasma endocan levels are associated with
      endothelial dysfunction in humans in vivo.
AB  - Although endothelial dysfunction is central to the pathogenesis of sepsis, no
      specific and clinically applicable marker for endothelial dysfunction is
      currently available. Endocan, a proteoglycan excreted by endothelial cells in
      response to inflammatory cytokines, may serve as such a marker. Our objective was
      to investigate the kinetics of endocan and its relationship with inflammation
      induced endothelial dysfunction during experimental human endotoxemia.
      Endothelial function was assessed in 17 healthy male volunteers before and 4 h
      after the administration of 2 ng/kg lipopolysaccharide (LPS) by determination of
      the vasodilatory response of forearm blood vessels to intra-arterial infusion of
      endothelium-dependent (acetylcholine) or endothelium-independent
      (nitroglycerin/sodium nitroprusside) vasodilators using venous occlusion
      plethysmography. Plasma levels of endocan, inflammatory cytokines, intercellular
      adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) were
      measured, and correlations with endothelial dysfunction were explored. Plasma
      levels of all measured cytokines, endocan, ICAM, and VCAM concentrations
      significantly increased after LPS administration. Furthermore, LPS administration
      resulted in a significantly blunted response to acetylcholine (mean +/- SD
      increase in forearm blood flow [FBF] of 383% +/- 320% before LPS vs. 173% +/-
      134% after LPS, P = 0.03), whereas the response to nitroglycerin/sodium
      nitroprusside was not affected (mean +/- SD increase in FBF of 174% +/- 120%
      before LPS vs. 110% +/- 82% after LPS, P = 0.11). Furthermore, there was a
      significant correlation between the increase in plasma endocan levels and the
      attenuation of vasodilatory responses to acetylcholine (r = -0.48, P < 0.05). No
      correlation existed between plasma levels of ICAM or VCAM and the attenuation of
      the acetylcholine-induced vasodilatory response. Endocan levels are related to
      endothelial dysfunction in humans in vivo during systemic inflammation evoked by
      experimental endotoxemia. Therefore, this study suggests that endocan could be a
      novel marker of endothelial dysfunction in inflammatory conditions. 

PMID- 25565644
TI  - Interleukin-7 and anti-programmed cell death 1 antibody have differing effects to
      reverse sepsis-induced immunosuppression.
AB  - Sepsis remains a major cause of morbidity and mortality in most intensive care
      units. Protracted sepsis can evolve into a state of profound immunosuppression
      characterized by secondary infections, frequently with opportunistic-type
      pathogens. Immunoadjuvant therapy is currently being evaluated as a novel
      treatment for patients with sepsis. Two of the most promising immunoadjuvants are
      interleukin-7 (IL-7) and anti-programmed cell death 1 antibody (anti-PD-1). Both
      IL-7 and anti-PD-1 have been reported to boost host immunity and improve outcomes
      in patients with viral infections and cancer. The purpose of this study was to
      define the immunological mechanisms of action of IL-7 and anti-PD-1 in the two
      hit sepsis model of cecal ligation and puncture followed by Candida albicans. In
      addition, we examined whether combined treatment with IL-7 and anti-PD-1 provided
      any additive beneficial effects in reversing immune dysfunction. The present
      findings demonstrated that IL-7 and anti-PD-1 had differing effects on innate and
      adaptive immune functions. Compared with anti-PD-1, IL-7 increased lymphocyte
      proliferation; expression of lymphocyte adhesion molecules, lymphocyte function
      associated antigen 1, and very late antigen-4; interferon-gamma production; and
      CD28 expression on splenic CD8 T cells. In contrast, anti-PD-1 seemed to have a
      greater effect on major histocompatibility complex class II expression on splenic
      macrophages and dendritic cells than IL-7. Combined treatment with IL-7 and anti
      PD-1 produced additive effects on CD28 expression, lymphocyte proliferation, and
      splenic secretion of interferon-gamma. In conclusion, the present study shows
      differences in immunomodulatory actions between IL-7 and anti-PD-1 and provides a
      potential rationale for combining IL-7 and anti-PD-1 in the therapy of sepsis. 

PMID- 25565646
TI  - Endogenous microparticles drive the proinflammatory host immune response in
      severely injured trauma patients.
AB  - INTRODUCTION: Severe trauma affects the immune system, which in its turn is
      associated with poor outcome. The mediators driving the immune responses in
      trauma are largely unknown. The aim of this study was to investigate the role of
      endogenous microparticles (MPs) in mediating the immune response following severe
      trauma. METHODS: A prospective, observational substudy of the ACIT II (Activation
      of Coagulation and Inflammation in Trauma II) study was performed at our academic
      level I trauma center. Adult multiple-trauma patients with an injury severity
      score of 15 or higher were included between May 2012 and June 2013. Ex vivo whole
      blood stimulation with lipopolysaccharide was performed on aseptically collected
      patient plasma containing MPs and in plasma depleted of MPs. Flow cytometry and
      transmission electronic microscopy were performed on plasma samples to
      investigate the numbers and cellular origin of MPs. Healthy individuals served as
      a control group. RESULTS: Ten trauma patients and 10 control subjects were
      included. Trauma patients were significantly injured with a median injury
      severity score of 19 (range, 17-45). Patients were neither in shock nor bleeding.
      On admission to the hospital, the host response to bacterial stimulation was
      blunted in trauma patients compared with control subjects, as reflected by
      decreased production of interleukin 6 (IL-6), IL-10, and tumor necrosis factor
      alpha (P < 0.001). In trauma patients, MP-positive plasma was associated with a
      significantly higher synthesis of IL-6 and tumor necrosis factor alpha compared
      with plasma depleted from MPs (P = 0.047 and 0.002, respectively). Compared with
      control subjects, the number of circulating MPs was significantly decreased in
      trauma patients (P = 0.009). Most MPs originated from platelets. Multiple
      cellular protrusions, which result in MP formation, were observed in plasma from
      trauma patients, but not in control subjects. CONCLUSIONS: On admission, trauma
      patients have a reduced immune response toward endotoxin challenge, which is, at
      least in part, mediated by MPs, which circulate in low numbers and in early
      stages. Most MPs originate from platelets, which indicates that these cells may
      be the most important source of MPs involved in initiating an inflammatory host
      response after injury.

PMID- 25565647
TI  - Catecholamine use is associated with enterocyte damage in critically ill
      patients.
AB  - Small bowel damage is frequent but underdiagnosed among critically ill patients
      with shock. High catecholamine doses may have a deleterious effect on mesenteric
      blood flow. Plasma intestinal fatty acid-binding protein (I-FABP) concentration
      is a marker of enterocyte damage, whereas plasma citrulline concentration is a
      marker of functional enterocyte mass. We hypothesized that high doses of
      catecholamines in critically ill patients may be associated with enterocyte
      damage. This study aimed to determine the link between catecholamine use and dose
      with enterocyte damage. This is a prospective observational study performed in a
      large regional university teaching hospital. Critically ill patients requiring
      epinephrine and/or norepinephrine at admission to a medical intensive care unit
      (ICU) were included, as well as controls not receiving catecholamines. We
      evaluated at admission plasma I-FABP and citrulline concentrations, abdominal
      perfusion pressure (APP), and variables relating to prognosis and treatment.
      Patients were categorized according to the quartiles of catecholamine dose at ICU
      admission. Sixty critically ill patients receiving catecholamines and 27 not
      receiving catecholamines were included. Plasma I-FABP was higher among patients
      receiving catecholamine than in controls. Among patients receiving
      catecholamines, a dose of 0.48 gamma kg min or more at ICU admission was
      associated with a higher I-FABP concentration. A Sepsis-related Organ Failure
      Assessment score higher than 11 and plasma I-FABP more than 524 pg mL at ICU
      admission were independently associated with 28-day mortality (odds ratio, 4.0
      [1.24-12.95] and odds ratio, 4.90 [1.44-16.6], respectively). Catecholamine use
      is associated with I-FABP elevation in critically ill patients. Critically ill
      patients receiving more than 0.48 gamma kg min of epinephrine and/or
      norepinephrine at ICU admission have high I-FABP concentrations. This suggests
      that enterocyte damage reflects the severity of shock, and an adverse effect of
      catecholamines per se is possible. 

PMID- 25565645
TI  - Creating a "Prosurvival Phenotype" Through Histone Deacetylase Inhibition: Past,
      Present, and Future.
AB  - Traumatic injuries and their sequelae represent a major source of mortality in
      the United States and globally. Initial treatment for shock, traumatic brain
      injury, and polytrauma is limited to resuscitation fluids to replace lost volume.
      To date, there are no treatments with inherent prosurvival properties. Our
      laboratory has investigated the use of histone deacetylase inhibitors (HDACIs) as
      pharmacological agents to improve survival. This class of drugs acts through
      posttranslational protein modifications and is a direct regulator of chromatin
      structure and function, as well as the function of numerous cytoplasmic proteins.
      In models of hemorrhagic shock and polytrauma, administration of HDACIs offers a
      significant survival advantage, even in the absence of fluid resuscitation.
      Positive results have also been shown in two-hit models of hemorrhage and sepsis
      and in hemorrhagic shock combined with traumatic brain injury. Accumulating data
      generated by our group and others continue to support the use of HDACIs for the
      creation of a prosurvival phenotype. With further research and clinical trials,
      HDACIs have the potential to be an integral tool in the treatment of trauma,
      especially in the prehospital phase. 

PMID- 25565648
TI  - Personality's association with IADLs in community dwelling older adults.
AB  - OBJECTIVES: Extant research has established several predictors of functional
      ability (FA) in older adults (OAs); however, one factor that has been relatively
      ignored is personality. Preliminary evidence suggests that openness and
      agreeableness are associated with instrumental activities of daily living
      (IADLs). However, how personality is related to IADLs remains unclear. We aimed
      to determine how personality factors predict performance of IADLs, which we
      hypothesized, was because of executive functioning (EF). METHODS: To best
      understand the relationship between personality and IADLs, we recruited and ran
      65 independent community dwelling OAs. Bivariate correlations and hierarchical
      regressions were completed to determine the associations between openness and
      agreeableness with IADLs. Lastly, mediation analyses were completed to examine
      our hypothesis that EF would mediate this relationship RESULTS: Correlation and
      regression findings support the relationship between openness and IADLs but not
      agreeableness and IADLs. As hypothesized, the relationship between openness and
      IADLs was mediated by EF. CONCLUSIONS: We replicated the relationship between
      openness and IADLs and extend the literature by showing the mechanism of action
      for this relationship is EF. While our mediation results support this
      perspective, future research should determine if interventions that increase OAs'
      EF, in turn, increase or attenuate decline in IADLs over time.

PMID- 25565649
TI  - Laser beam controlled drug release from Ce6-gold nanorod composites in living
      cells: a FLIM study.
AB  - A new method to image drug release from drug-nanoparticle composites in living
      cells was established. The composites of silica coated gold nanorods (AuNR@SiO2)
      and chlorine e6 (Ce6) photosensitizers (AuNR@SiO2-Ce6) were formed by
      electrostatic force with a Ce6 loading efficiency of 80%. The strong resonance
      absorptions of AuNR@SiO2-Ce6 in the near-infrared (NIR) region enabled the
      effective release of Ce6 from AuNR@SiO2-Ce6 by 780 nm CW laser irradiation. The
      780 nm laser beam was applied to not only control the releasing amount of Ce6
      from cellular AuNR@SiO2-Ce6 by adjusting the irradiation dose (time), but also to
      spatially confine the Ce6 release in cells by focusing the laser beam on the
      target sites. Furthermore, the fluorescence lifetime of Ce6 was found to change
      drastically from 0.9 ns in the AuNR@SiO2-Ce6 complex to 6 ns after release, and
      therefore fluorescence lifetime imaging microscopy (FLIM) was introduced to image
      the photo-induced Ce6 release in living cells. Finally, the controllable killing
      effect of photodynamic cancer therapy (PDT) using AuNR@SiO2-Ce6 was demonstrated
      by changing the released amount of Ce6, which indicates that AuNR@SiO2-Ce6 is
      promising for targeted tumour PDT. 

PMID- 25565650
TI  - Association between smoking and depression in patients with type 2 diabetes.

PMID- 25565651
TI  - Radiographic skeletal survey for non-accidental injury: systematic review and
      development of a national New Zealand protocol.
AB  - INTRODUCTION: Clinically occult fractures from non-accidental injury (NAI) are
      best detected on radiographic skeletal survey. However, there are regional
      variations regarding the views included in such surveys. We undertook a
      systematic review of the evidence supporting skeletal survey protocols to design
      a protocol that could be implemented across New Zealand. METHODS: In June 2013,
      we searched Medline, Google Scholar, the Cochrane database, UpToDate and relevant
      reference lists for English-language publications on skeletal survey in NAI from
      1946. We included publications that contained a protocol or reported evidence
      supporting including, or excluding, specific views in a skeletal survey. All
      included publications were critically appraised. Based on this systematic review,
      a draft protocol was developed and presented to an Australian and New Zealand
      Society for Paediatric Radiology NAI symposium in October 2013. Feedback from the
      symposium and later discussions was incorporated into the final protocol.
      RESULTS: We identified 2 guidelines for skeletal survey, 13 other protocols and
      15 articles providing evidence for inclusion of specific images in a skeletal
      survey. The guidelines scored poorly on critical appraisal of several aspects of
      their methods. We found no studies that validate any of the protocols or compare
      their performance. Evidence supporting inclusion in a skeletal survey is limited
      to ribs, spine, pelvis, hands and feet, and long bone views. Our final protocol
      is a standardised, two-tiered protocol consisting of between 17 and 22 views.
      CONCLUSION: A standardised protocol for radiographic skeletal survey protocol has
      been developed in New Zealand. We present it here for consideration by others.

PMID- 25565652
TI  - HDlive imaging of meconium peritonitis.

PMID- 25565654
TI  - Preoperative evaluation of the confluent drainage veins to the gastrocolic trunk
      of Henle: understanding the surgical vascular anatomy during
      pancreaticoduodenectomy.
AB  - BACKGROUND: The aim of this study was to classify the variations of the
      anatomical tributaries of the colic drainage veins into the gastrocolic trunk of
      Henle detected by three-dimensional multidetector computed tomography to
      understand the surgical vascular anatomy during pancreaticoduodenectomy. METHODS:
      One hundred and twenty patients who underwent three-dimensional multidetector
      computed tomography studies before pancreaticoduodenectomy were retrospectively
      reviewed. RESULTS: The gastrocolic trunk of Henle was identified in 100 patients
      (83.3%) by three-dimensional multidetector computed tomography. The anatomical
      tributaries of the gastrocolic trunk of Henle described by three-dimensional
      multidetector computed tomography were classified into four types based on the
      number of veins (superior right colic vein, right colic vein and middle colic
      vein) that drained into the gastrocolic trunk of Henle, as follows: Type-0 (no
      colic drainage veins), -I (one colic drainage vein), -II (two colic drainage
      veins) and -III (three colic drainage veins). The frequencies of Type-0, Type-I,
      Type-II and Type-III were 7% (n = 7), 71% (n = 71), 20% (n = 20) and 2% (n = 2),
      respectively. CONCLUSIONS: Three-dimensional multidetector computed tomography
      can provide clinically useful information about the confluent colic drainage
      veins to gastrocolic trunk of Henle during pancreaticoduodenectomy.

PMID- 25565655
TI  - Extraction and enrichment of polycyclic aromatic hydrocarbons by ordered
      mesoporous carbon reinforced hollow fiber liquid-phase microextraction.
AB  - A novel microextraction method, ordered mesoporous carbon reinforced hollow fiber
      liquid-phase microextraction coupled with high-performance liquid chromatography
      and fluorescence detection, was developed for the determination of some organic
      pollutants in water samples. Four polycyclic aromatic hydrocarbons (fluorene,
      anthracene, fluoranthene, and pyrene) were selected to validate this new method.
      Main parameters that could influence the extraction efficiency such as extraction
      time, fiber length, stirring rate, the type of the extraction solvent, pH value,
      the concentration of ordered mesoporous carbon, and salt effect were optimized.
      Under the optimal extraction conditions, good linearity was observed in the range
      of 2-1000 ng/L, with the correlation coefficients of 0.9954-0.9986. The
      recoveries for the spiked samples were in the range of 88.96-100.17%. The limits
      of detection of the method were 0.4-4 ng/L. The relative standard deviations
      varied from 4.2-5.9%. The results demonstrated that the newly developed method
      was an efficient pretreatment and enrichment procedure for the determination of
      polycyclic aromatic hydrocarbons in environmental water samples. 

PMID- 25565653
TI  - The role of alterations in mitochondrial dynamics and PGC-1alpha over-expression
      in fast muscle atrophy following hindlimb unloading.
AB  - KEY POINTS: Skeletal muscle atrophy occurs as a result of disuse. Although
      several studies have established that a decrease in protein synthesis and
      increase in protein degradation lead to muscle atrophy, little is known about the
      triggers underlying such processes. A growing body of evidence challenges
      oxidative stress as a trigger of disuse atrophy; furthermore, it is also becoming
      evident that mitochondrial dysfunction may play a causative role in determining
      muscle atrophy. Mitochondrial fusion and fission have emerged as important
      processes that govern mitochondrial function and PGC-1alpha may regulate
      fusion/fission events. Although most studies on mice have focused on the anti
      gravitary slow soleus muscle as it is preferentially affected by disuse atrophy,
      several fast muscles (including gastrocnemius) go through a significant loss of
      mass following unloading. Here we found that in fast muscles an early down
      regulation of pro-fusion proteins, through concomitant AMP-activated protein
      kinase (AMPK) activation, can activate catabolic systems, and ultimately cause
      muscle mass loss in disuse. Elevated muscle PGC-1alpha completely preserves
      muscle mass by preventing the fall in pro-fusion protein expression, AMPK and
      catabolic system activation, suggesting that compounds inducing PGC-1alpha
      expression could be useful to treat and prevent muscle atrophy. ABSTRACT: The
      mechanisms triggering disuse muscle atrophy remain of debate. It is becoming
      evident that mitochondrial dysfunction may regulate pathways controlling muscle
      mass. We have recently shown that mitochondrial dysfunction plays a major role in
      disuse atrophy of soleus, a slow, oxidative muscle. Here we tested the hypothesis
      that hindlimb unloading-induced atrophy could be due to mitochondrial dysfunction
      in fast muscles too, notwithstanding their much lower mitochondrial content.
      Gastrocnemius displayed atrophy following both 3 and 7 days of unloading. SOD1
      and catalase up-regulation, no H2 O2 accumulation and no increase of protein
      carbonylation suggest the antioxidant defence system efficiently reacted to redox
      imbalance in the early phases of disuse. A defective mitochondrial fusion (Mfn1,
      Mfn2 and OPA1 down-regulation) occurred together with an impairment of OXPHOS
      capacity. Furthermore, at 3 days of unloading higher acetyl-CoA carboxylase (ACC)
      phosphorylation was found, suggesting AMP-activated protein kinase (AMPK) pathway
      activation. To test the role of mitochondrial alterations we used Tg-mice
      overexpressing PGC-1alpha because of the known effect of PGC-1alpha on
      stimulation of Mfn2 expression. PGC-alpha overexpression was sufficient to
      prevent (i) the decrease of pro-fusion proteins (Mfn1, Mfn2 and OPA1), (ii)
      activation of the AMPK pathway, (iii) the inducible expression of MuRF1 and
      atrogin1 and of authopagic factors, and (iv) any muscle mass loss in response to
      disuse. As the effects of increased PGC-1alpha activity were sustained throughout
      disuse, compounds inducing PGC-1alpha expression could be useful to treat and
      prevent muscle atrophy also in fast muscles.

PMID- 25565656
TI  - Effects of steroids on thrombogenic markers in patients undergoing unilateral
      total knee arthroplasty: a prospective, double-blind, randomized controlled
      trial.
AB  - Venous thromboembolism (VTE) remains an important complication after total knee
      arthroplasty (TKA). Systemic thrombin generation starts perioperatively.
      Inflammation, characterized by a rise in interleukin-6 (IL6), initiates the
      coagulation cascade, but low-dose steroids can reduce post-TKA IL6 levels. This
      double-blinded, randomized, placebo-controlled study enrolled 30 patients
      undergoing unilateral TKA to assess the effect of perioperative steroids on serum
      prothrombin fragment (PF1.2), a marker of thrombin generation, and plasmin-alpha
      2-antiplasmin complex (PAP), a marker of fibrinolysis. Study patients received
      100 mg of intravenous hydrocortisone 2 h prior to surgery, and controls received
      normal saline. Blood samples, drawn pre-incision and at 4 h post tourniquet
      release, were assayed for PF1.2 and PAP. The study group had significantly lower
      mean PF1.2 at 4 h compared to controls (616 +/- 358 pMol/L vs. 936 +/- 332
      pMol/L, p = 0.037). The mean rise in PF1.2 in the control group was significantly
      greater compared to the study group (672 +/- 173 pMol/L vs. 350 +/- 211 pMol/L, p
      < 0.001). Mean PAP was higher in the study group at 4 h (1639 +/- 823 ug/L vs.
      1087 +/- 536 ug/L), but did not reach statistical significance (p = 0.07). These
      results may have clinical implications in terms of postoperative VTE risk and
      management.

PMID- 25565657
TI  - Compound heterozygous mutations of ABCB11 responsible for benign recurrent
      intrahepatic cholestasis.

PMID- 25565659
TI  - Wear and tear vision.

PMID- 25565658
TI  - Insulin resistance and white adipose tissue inflammation are uncoupled in
      energetically challenged Fsp27-deficient mice.
AB  - Fsp27 is a lipid droplet-associated protein almost exclusively expressed in
      adipocytes where it facilitates unilocular lipid droplet formation. In mice,
      Fsp27 deficiency is associated with increased basal lipolysis, 'browning' of
      white fat and a healthy metabolic profile, whereas a patient with congenital
      CIDEC deficiency manifested an adverse lipodystrophic phenotype. Here we
      reconcile these data by showing that exposing Fsp27-null mice to a substantial
      energetic stress by crossing them with ob/ob mice or BATless mice, or feeding
      them a high-fat diet, results in hepatic steatosis and insulin resistance. We
      also observe a striking reduction in adipose inflammation and increase in
      adiponectin levels in all three models. This appears to reflect reduced
      activation of the inflammasome and less adipocyte death. These findings highlight
      the importance of Fsp27 in facilitating optimal energy storage in adipocytes and
      represent a rare example where adipose inflammation and hepatic insulin
      resistance are disassociated. 

PMID- 25565660
TI  - Effects of interaural pitch matching and auditory image centering on binaural
      sensitivity in cochlear implant users.
AB  - OBJECTIVES: In bilateral cochlear implant users, electrodes mapped to the same
      frequency range in each ear may stimulate different places in each cochlea due to
      an insertion depth difference of electrode arrays. This interaural place of
      stimulation mismatch can lead to problems with auditory image fusion and
      sensitivity to binaural cues, which may explain the large localization errors
      seen in many patients. Previous work has shown that interaural place of
      stimulation mismatch can lead to off-centered auditory images being perceived
      even though interaural time and level differences (ITD and ILD, respectively)
      were zero. Large interaural mismatches reduced the ability to use ITDs for
      auditory image lateralization. In contrast, lateralization with ILDs was still
      possible but the mapping of ILDs to spatial locations was distorted. This study
      extends the previous work by systematically investigating the effect of
      interaural place of stimulation mismatch on ITD and ILD sensitivity directly and
      examining whether "centering" methods can be used to mitigate some of the
      negative effects of interaural place of stimulation mismatch. DESIGN: Interaural
      place of stimulation mismatch was deliberately introduced for this study.
      Interaural pitch-matching techniques were used to identify a pitch-matched pair
      of electrodes across the ears approximately at the center of the array.
      Mismatched pairs were then created by maintaining one of the pitch-matched
      electrodes constant, and systematically varying the contralateral electrode by
      two, four, or eight electrode positions (corresponding to approximately 1.5, 3,
      and 6 mm of interaural place of excitation differences). The stimuli were 300
      msec, constant amplitude pulse trains presented at 100 pulses per second. ITD and
      ILD just noticeable differences (JNDs) were measured using a method of constant
      stimuli with a two-interval, two-alternative forced choice task. The results were
      fit with a psychometric function to obtain the JNDs. In experiment I, ITD and ILD
      JNDs were measured as a function of the simulated place of stimulation mismatch.
      In experiment II, the auditory image of mismatched pair was centered by adjusting
      the stimulation level according to a lateralization task. ITD and ILD JNDs were
      then remeasured and compared with the results of experiment I. RESULTS: ITD and
      ILD JNDs were best (lowest thresholds) for pairs of electrodes at or near the
      pitch-matched pair. Thresholds increased systematically with increasing amounts
      of interaural mismatch. Deliberate and careful centering of auditory images did
      not significantly improve ITD JNDs but did improve ILD JNDs at very large amounts
      of simulated mismatch. CONCLUSIONS: Interaural place of stimulation mismatch
      decreases sensitivity to binaural cues that are important for accurate sound
      localization. However, deliberate and careful centering of auditory images does
      not seem to significantly counteract the effects of mismatch. Hence, to obtain
      maximal sound localization benefits of bilateral implantation, clinical and
      surgical techniques are needed that take into account differences in electrode
      array insertion depths across the ears.

PMID- 25565661
TI  - Between-Frequency and Between-Ear Gap Detections and Their Relation to Perception
      of Stop Consonants.
AB  - OBJECTIVES: The objective of this study was to examine the hypothesis that
      between-channel gap detection, which includes between-frequency and between-ear
      gap detection, and perception of stop consonants, which is mediated by the length
      of voice-onset time (VOT), share common mechanisms, namely relative-timing
      operation in monitoring separate perceptual channels. DESIGN: The authors
      measured gap detection thresholds and identification functions of /ba/ and /pa/
      along VOT in 49 native young adult Japanese listeners. There were three gap
      detection tasks. In the between-frequency task, the leading and trailing markers
      differed in terms of center frequency (Fc). The leading marker was a broadband
      noise of 10 to 20,000 Hz. The trailing marker was a 0.5-octave band-passed noise
      of 1000-, 2000-, 4000-, or 8000-Hz Fc. In the between-ear task, the two markers
      were spectrally identical but presented to separate ears. In the within-frequency
      task, the two spectrally identical markers were presented to the same ear. The
      /ba/-/pa/ identification functions were obtained in a task in which the listeners
      were presented synthesized speech stimuli of varying VOTs from 10 to 46 msec and
      asked to identify them as /ba/ or /pa/. RESULTS: The between-ear gap thresholds
      were significantly positively correlated with the between-frequency gap
      thresholds (except those obtained with the trailing marker of 4000-Hz Fc). The
      between-ear gap thresholds were not significantly correlated with the within
      frequency gap thresholds, which were significantly correlated with all the
      between-frequency gap thresholds. The VOT boundaries and slopes of /ba/-/pa/
      identification functions were not significantly correlated with any of these gap
      thresholds. CONCLUSIONS: There was a close relation between the between-ear and
      between-frequency gap detection, supporting the view that these two types of gap
      detection share common mechanisms of between-channel gap detection. However,
      there was no evidence for a relation between the perception of stop consonants
      and the between-frequency/ear gap detection in native Japanese speakers.

PMID- 25565663
TI  - The nature of photocatalytic "water splitting" on silicon nanowires.
AB  - Silicon should be an ideal semiconductor material if it can be proven usable for
      photocatalytic water splitting, given its high natural abundance. Thus it is
      imperative to explore the possibility of water splitting by running
      photocatalysis on a silicon surface and to decode the mechanism behind it. It is
      reported that hydrogen gas can indeed be produced from Si nanowires when
      illuminated in water, but the reactions are not a real water-splitting process.
      Instead, the production of hydrogen gas on the Si nanowires occurs through the
      cleavage of Si-H bonds and the formation of Si-OH bonds, resulting in the low
      probability of generating oxygen. On the other hand, these two types of surface
      dangling bonds both extract photoexcited electrons, whose competition greatly
      impacts on carrier lifetime and reaction efficiency. Thus surface chemistry holds
      the key to achieving high efficiency in such a photocatalytic system.

PMID- 25565662
TI  - Hearing Impairment in Relation to Severity of Diabetes in a Veteran Cohort.
AB  - OBJECTIVE: Type 2 diabetes is epidemic among veterans, approaching three times
      the prevalence of the general population. Diabetes leads to devastating
      complications of vascular and neurologic malfunction and appears to impair
      auditory function. Hearing loss prevention is a major health-related initiative
      in the Veterans Health Administration. Thus, this research sought to identify,
      and quantify with effect sizes, differences in hearing, speech recognition, and
      hearing-related quality of life (QOL) measures associated with diabetes and to
      determine whether well-controlled diabetes diminishes the differences. DESIGN:
      The authors examined selected cross-sectional data from the baseline (initial)
      visit of a longitudinal study of Veterans with and without type 2 diabetes
      designed to assess the possible differences in age-related trajectories of
      peripheral and central auditory function between the two groups. In addition, the
      diabetes group was divided into subgroups on the basis of medical diagnosis of
      diabetes and current glycated hemoglobin (HbA1c) as a metric of disease severity
      and control. Outcome measures were pure-tone thresholds, word recognition using
      sentences presented in noise or time-compressed, and an inventory assessing the
      self-perceived impact of hearing loss on QOL. Data were analyzed from 130
      Veterans ages 24 to 73 (mean 48) years with well-controlled (controlled)
      diabetes, poorly controlled (uncontrolled) diabetes, prediabetes, and no
      diabetes. Regression was used to identify any group differences in age, noise
      exposure history, and other sociodemographic factors, and multiple regression was
      used to model each outcome variable, adjusting for potential confounders. Results
      were evaluated in relation to diabetes duration, use of insulin (yes, no), and
      presence of selected diabetes complications (neuropathy and retinopathy).
      RESULTS: Compared with nondiabetics, Veterans with uncontrolled diabetes had
      significant differences in hearing at speech frequencies, including poorer
      hearing by 3 to 3.5 dB for thresholds at 250 Hz and in a clinical pure-tone
      average, respectively. Compared with nondiabetic controls, individuals with
      uncontrolled diabetes also significantly more frequently reported that their
      hearing adversely impacted QOL on one of the three subscales (ability to adapt).
      Despite this, although they also had slightly poorer mean scores on both word
      recognition tasks performed, these differences did not reach statistical
      significance and all subjects performed well on these tasks. Compared with
      Veterans with controlled diabetes, those with uncontrolled disease tended to have
      had diabetes longer, be insulin-dependent, and have a greater prevalence of
      diabetic retinopathy. Results are generally comparable with the literature with
      regard to the magnitude of threshold differences and the prevalence of hearing
      impairment but extend prior work by providing threshold difference and hearing
      loss prevalence effect sizes by category of diabetes control and by including
      additional functional measures. CONCLUSIONS: In a cohort of Veterans with type 2
      diabetes and relatively good hearing, significant effects of disease severity
      were found for hearing thresholds at a subset of frequencies and for one of the
      three QOL subscales. Significant differences were concentrated among those with
      poorly controlled diabetes based on current HbA1c. Results provide evidence that
      the observed hearing dysfunction in type 2 diabetes might be prevented or delayed
      through tight metabolic control. Findings need to be corroborated using
      longitudinal assessments.

PMID- 25565664
TI  - Thermal-aided phosvitin extraction from egg yolk.
AB  - BACKGROUND: Phosvitin is the principal phosphoprotein in egg yolk and has great
      potential for use as a functional food ingredient in improving bone health. This
      study reports a thermal-aided extraction method without using organic solvents or
      non-food-compatible chemicals. RESULTS: Egg yolk was two times diluted with water
      and then extracted by 100 g L(-1) NaCl. Effects of pH and heating temperature on
      the extract were examined. The phosvitin purity increased from 75.7% at pH 8.0 to
      80.1% at pH 5.0 and then started to decrease, but the yield decreased at
      decreasing pHs. The phosvitin purity increased at increasing temperature up to 90
      degrees C and then started to decrease at 95  degrees C, while the yield
      increased from 70 to 80  degrees C and then started to decline at 85  degrees C.
      CONCLUSION: A purity of 88.0% and a yield of 23.5 g kg(-1) yolk dry matter were
      obtained at 90  degrees C. The purity and yield were comparable to or higher than
      those of previously methods. The method developed in this study is simple,
      including mainly two steps, i.e. water dilution of egg yolk and NaCl extraction
      with heating, and can be scaled up for industrial production.

PMID- 25565666
TI  - Enhanced electron penetration through an ultrathin graphene layer for highly
      efficient catalysis of the hydrogen evolution reaction.
AB  - Major challenges encountered when trying to replace precious-metal-based
      electrocatalysts of the hydrogen evolution reaction (HER) in acidic media are
      related to the low efficiency and stability of non-precious-metal compounds.
      Therefore, new concepts and strategies have to be devised to develop
      electrocatalysts that are based on earth-abundant materials. Herein, we report a
      hierarchical architecture that consists of ultrathin graphene shells (only 1-3
      layers) that encapsulate a uniform CoNi nanoalloy to enhance its HER performance
      in acidic media. The optimized catalyst exhibits high stability and activity with
      an onset overpotential of almost zero versus the reversible hydrogen electrode
      (RHE) and an overpotential of only 142 mV at 10 mA cm(-2) , which is quite close
      to that of commercial 40 % Pt/C catalysts. Density functional theory (DFT)
      calculations indicate that the ultrathin graphene shells strongly promote
      electron penetration from the CoNi nanoalloy to the graphene surface. With
      nitrogen dopants, they synergistically increase the electron density on the
      graphene surface, which results in superior HER activity on the graphene shells. 

PMID- 25565665
TI  - HIF-2 Inhibition Supresses Inflammatory Responses and Osteoclastic
      Differentiation in Human Periodontal Ligament Cells.
AB  - Recent reports suggest that hypoxia inducible factor-2alpha (HIF-2alpha) is a key
      regulator of osteoarthritis cartilage destruction. However, the precise role of
      HIF-2alpha in the inflammatory response and osteoclast differentiation remains
      unclear. The purpose of this study was to investigate the effect of HIF-2alpha on
      inflammatory cytokines, extracellular matrix (ECM) destruction enzymes, and
      osteoclastic differentiation in nicotine and lipopolysaccharide (LPS)-stimulated
      human periodontal ligament cells (PDLCs). HIF-2alpha was upregulated in
      chronically inflamed PDLCs of periodontitis patients, and in nicotine- and LPS
      exposed PDLC in dose- and time-dependent manners. HIF-2alpha inhibitor and HIF
      2alpha siRNA attenuated the nicotine- and LPS- induced production of NO and PGE2
      , upregulation of iNOS, COX-2, pro-inflammatory cytokines (IL-1beta, TNF-alpha,
      IL-1beta, IL-6, IL-8, IL-10, IL-11, and IL-17), and matrix metalloproteinases
      (MMPs; MMP-1, -8, -13, -2 and -9), and reversed the effect on TIMPs (TIMP-1 and 
      2) in PDLCs. The conditioned medium produced by nicotine and LPS-treated PDLCs
      increased the number of TRAP-stained osteoclasts, TRAP activity and osteoclast
      specific genes, which has been blocked by HIF-2alpha inhibition and silencing.
      HIF-2alpha inhibitor and HIF-2alpha siRNA inhibited the effects of nicotine and
      LPS on the activation of Akt, JAK2 and STAT3, ERK and JNK MAPK, nuclear factor
      kappaB, c-Jun, and c-Fos. Taken together, this study is the first to demonstrate
      that HIF-2alpha inhibition exhibits anti-inflammatory activity through the
      inhibition of inflammatory cytokines and impairment of ECM destruction, as well
      as blocking of osteoclastic differentiation in a nicotine- and periodontopathogen
      stimulated PDLCs model. Thus, HIF-2alpha inhibition may be a novel molecular
      target for therapeutic approaches in periodontitis.

PMID- 25565668
TI  - Patterns of Drugs and Drug Metabolites Observed in Meconium: What Do They Mean?
AB  - BACKGROUND: Meconium drug testing is performed to detect potentially harmful drug
      exposures in a newborn. Interpretation of meconium drug testing results can be
      complicated based on the patterns and proportional concentrations of the drug(s)
      and/or drug metabolite(s) detected. METHODS: The objective of this study was to
      analyze meconium drug testing patterns in a de-identified dataset from a national
      reference laboratory (n = 76,631) and in a subset of the data, wherein specimens
      originated at a single academic medical center for which detailed chart review
      was possible (n = 3635). Meconium testing was performed using 11 immunoassay
      based drug screens. Specimens that were positive for one or more drug screens
      were reflexed to corresponding confirmation tests performed by gas chromatography
      or liquid chromatography with mass spectrometric detection, targeted to identify
      and quantitate specific parent drug(s) and metabolite(s). RESULTS: The positivity
      rate was the highest for the cannabis metabolite 11-nor-9-carboxy-delta-9
      tetrahydrocannabinol (25.2%, n = 18,643), followed by opiates/oxycodone (23.2%, n
      = 17,778), amphetamine/methamphetamine (6.7%, n = 5134), cocaine metabolites
      (5.5%, n = 4205), methadone (5.3%, n = 4093), benzodiazepines (3.4%, n = 2603),
      barbiturates (1.1%, n = 834), propoxyphene (1.0%, n = 749), and phencyclidine
      (0.1%, n = 44). Based on documented pharmacy history, drugs administered to
      either the mother or newborn during the birth hospitalization were detected in
      meconium, providing evidence that drugs can be incorporated into meconium
      rapidly. Drugs administered directly to the newborn after birth were recovered in
      meconium as both parent drug and metabolites, providing evidence of neonatal
      metabolism. Overall, patterns observed in meconium exhibited many similarities to
      those patterns commonly reported with urine drug testing. CONCLUSIONS:
      Interpretation of meconium drug testing results requires comparison of results
      with clinical and analytical expectations, including maternal admissions to drug
      use, pharmacy history, recognized metabolic patterns for drugs of interest,
      cutoff concentrations, and other performance characteristics of the test.
      Concentrations of drug(s) and drug metabolites(s) may not reliably predict timing
      of drug use, extent of drug use, or frequency of drug exposures.

PMID- 25565669
TI  - Limited Sampling Strategy for Mycophenolic Acid in Chinese Kidney Transplant
      Recipients Receiving Enteric-Coated Mycophenolate Sodium and Tacrolimus During
      the Early Posttransplantation Phase.
AB  - BACKGROUND: Mycophenolic acid (MPA), a potent immunosuppressant, is widely used
      in solid organ transplantations. This study aimed to investigate the
      pharmacokinetics of enteric-coated mycophenolate sodium (EC-MPS) in Chinese adult
      renal allograft recipients and to generate optimal model equations for estimation
      of the MPA area under the concentration-time curve from 0 to 12 hours (AUC0-12
      h), using a limited sampling strategy (LSS). METHODS: Serial blood samples were
      collected over 12 hours from 38 recipients of a primary living-related donor
      kidney graft treated with EC-MPS, tacrolimus, and corticosteroid. MPA
      concentrations were evaluated using an enzyme-multiplied immunoassay technique.
      The LSSs were developed and validated by multiple regression analysis using a 2
      group method (test group, n = 19; validation group, n = 19). RESULTS: The best
      algorithms obtained from the test group were the following: 15.09 + 1.05 * C1.5 +
      1.8 * C4 + 4.18 * C6 (for 3 time points, r = 0.902) and 10.44 + 0.7 * C1 + 1.22 *
      C2 + 1.75 * C4 + 4.36 * C6 (for 4 time points, r = 0.941). When these algorithms
      were tested in the validation group, there were no significant differences in
      prediction errors. CONCLUSIONS: LSSs using time points of 1.5, 4, and 6 hours or
      1, 2, 4, and 6 hours after dose provide effective and reliable estimations of the
      MPA AUC0-12 h in Chinese renal allograft recipients treated concomitantly with EC
      MPS and tacrolimus during the early posttransplantation phase.

PMID- 25565670
TI  - Glutathione Transferase Gene Variants Influence Busulfan Pharmacokinetics and
      Outcome After Myeloablative Conditioning.
AB  - BACKGROUND: Busulfan (Bu) and cyclophosphamide (Cy) are frequently included in
      conditioning regimens before hematopoietic stem cell transplantation (HSCT). Both
      drugs are detoxified by glutathione transferases (GST), and GST gene variants may
      explain some of the interindividual variability in pharmacokinetics and drug
      toxicity. METHODS: The study investigated adult patients (n = 114) receiving oral
      Bu pre-HSCT. Bu doses were adjusted to obtain an average steady-state
      concentration (Css) of 900 mcg/L. RESULTS: Median first dose Bu Css was 1000
      mcg/L (600-1780 mcg/L). Patients carrying 1 and 2 GSTA1*B (rs3957357) alleles
      demonstrated median 12% and 16% higher Bu Css (P <= 0.05). Bu exposure (average
      Css; odds ratio = 1.009, 95% confidence interval = 1.002-1.017, P = 0.013) and
      GSTM1 gene copy number (odds ratio = 17.1, 95% confidence interval = 1.46-201, P
      = 0.024) were significant predictors of mortality <=30 days. The mortality was
      25% versus 2% among carriers of 2 versus no GSTM1 copies (P = 0.021). Mortality
      <=3 months was associated with higher first dose Bu exposure (1090 versus 980
      mcg/L, P = 0.021). GSTM1 expression and high Bu exposure may increase Cy toxicity
      by reducing intracellular glutathione. CONCLUSIONS: GST genotyping before HSCT
      may allow better prediction of Bu pharmacokinetics and drug toxicity, and thereby
      improve outcome after BuCy conditioning.

PMID- 25565667
TI  - Irinotecan treatment and senescence failure promote the emergence of more
      transformed and invasive cells that depend on anti-apoptotic Mcl-1.
AB  - Induction of senescence by chemotherapy was initially characterized as a
      suppressive response that prevents tumor cell proliferation. However, in response
      to treatment, it is not really known how cells can survive senescence and how
      irreversible this pathway is. In this study, we analyzed cell escape in response
      to irinotecan, a first line treatment used in colorectal cancer that induced
      senescence. We detected subpopulations of cells that adapted to chemotherapy and
      resumed proliferation. Survival led to the emergence of more transformed cells
      that induced tumor formation in mice and grew in low adhesion conditions. A
      significant amount of viable polyploid cells was also generated following
      irinotecan failure. Markers such as lgr5, CD44, CD133 and ALDH were downregulated
      in persistent clones, indicating that survival was not associated with an
      increase in cancer initiating cells. Importantly, malignant cells which resisted
      senescence relied on survival pathways induced by Mcl-1 signaling and to a lesser
      extent by Bcl-xL. Depletion of Mcl-1 increased irinotecan efficiency, induced the
      death of polyploid cells, prevented cell emergence and inhibited growth in low
      adhesion conditions. We therefore propose that Mcl-1 targeting should be
      considered in the future to reduce senescence escape and to improve the treatment
      of irinotecan-refractory colorectal cancers. 

PMID- 25565672
TI  - Effect of Genetic Polymorphism of CYP3A5 and CYP2C19 and Concomitant Use of
      Voriconazole on Blood Tacrolimus Concentration in Patients Receiving
      Hematopoietic Stem Cell Transplantation.
AB  - BACKGROUND: Blood tacrolimus (TAC) concentration delivered via intravenous
      administration is known to be influenced by genetic polymorphism of CYP3A5 and
      interaction with triazole antifungal agents. However, interindividual variability
      of blood TAC concentration is as of yet still difficult to predict during the
      early stages of hematopoietic stem cell transplantation (HSCT). This study was
      conducted to assess the wide variability of blood TAC concentrations because of
      the hepatic metabolic activities of CYP3A and CYP2C19 in HSCT recipients.
      METHODS: This study is a single-institute prospective study that includes 21
      adult patients who underwent HSCT and received 24 hours continuous intravenous
      administration of TAC at the Mie University Hospital between January 2009 and
      March 2014. After HSCT, the changes in blood TAC concentration/dose (C/D) ratio
      and TAC dose reduction from initial dose were investigated. RESULTS: Significant
      differences between HSCT recipients with CYP3A5*1 allele and CYP3A5*3/*3 genotype
      were observed with respect to the median TAC C/D ratio on day 14 (563 versus 742
      ng/mL per mg/kg, P < 0.01) and day 21 (672 versus 777 ng/mL per mg/kg, P < 0.05)
      after HSCT. Concomitant administration of voriconazole (VRCZ), but not of
      lansoprazole, was found to significantly increase the median TAC C/D ratio on day
      14 (557 versus 723 ng/mL per mg/kg, P < 0.01). Possession of the CYP3A5*3/*3
      genotype (day 14: odds ratio, 32.2; day 21: odds ratio, 33.0; P < 0.05) and
      concomitant administration of VRCZ (day 14: odds ratio, 37.8; P < 0.05) were
      found to be independent risk factors, which significantly contributed to an
      increased TAC C/D ratio. In HSCT recipients with CYP3A5*3/*3 genotype (78.0%),
      the median TAC dose ratio (day 21/day -1) was significantly lower compared with
      HSCT recipients with the CYP3A5*1 allele (94.1%), whereas VRCZ administration
      itself had no significant influence. Interestingly, in HSCT recipients with
      CYP2C19*1/*1, we found that the influence of VRCZ on the TAC dose ratio (85.7%)
      was relatively mild, even in a recipient with CYP3A5*3/*3. CONCLUSIONS: In HSCT
      recipients, the variability of intravenous TAC concentration in the blood could
      be explained in part by the genetic variation of CYP3A5. The study results also
      strongly imply that the magnitude of hepatic interaction between TAC and VRCZ is
      affected by the genetic polymorphism of both CYP3A5 and CYP2C19 genes.

PMID- 25565671
TI  - Therapeutic Drug Monitoring of Selective Serotonin Reuptake Inhibitors in Elderly
      Patients.
AB  - BACKGROUND: Elderly patients are at increased risk for elevated serum
      concentrations from treatment with selective serotonin reuptake inhibitors
      (SSRIs). The aim of this study was to examine the use of therapeutic drug
      monitoring (TDM) of SSRIs in elderly compared with younger patients. METHODS: All
      serum concentration measurements of SSRIs (escitalopram, citalopram, fluoxetine,
      fluvoxamine, paroxetine, and sertraline) performed at our laboratory in 2011 were
      included. The use of TDM (relative frequency) in older versus younger patients
      was examined by comparing the use of TDM in patients aged 60 years or older with
      that in patients younger than 60 years and by evaluating the use of TDM relative
      to age (age groups in decennials). The number of patients with an SSRI dispensed
      by prescription in the same region and period (the Norwegian Prescription
      Database) was used as reference. Additionally, the number of samples above the
      upper limit of the recommended reference range in patients aged 60 years or older
      and patients younger than 60 years was evaluated. RESULTS: TDM of an SSRI had
      been performed in 6333 patients. For all SSRIs, the use of TDM was significantly
      lower (8.2% versus 10.6% for citalopram, 10.0% versus 13.8% for escitalopram,
      8.6% versus 17.0% for fluoxetine, 5.6% versus 10.3% for paroxetine, and 8.1%
      versus 15.0% for sertraline) in patients aged 60 years or older compared with
      those younger than 60 years (P < 0.001). There was a gradual decline in the use
      of TDM with increasing age, with a 3-fold difference between the youngest (10-19)
      and oldest (90+) patients (P < 0.0001). The percentage of samples above the upper
      limit of the recommended reference range was 2-fold higher in patients aged 60
      years or older (6.7%) compared with patients younger than 60 (3.4%) years (P <
      0.0001). CONCLUSIONS: Clinical follow-up of patients with TDM of SSRIs is less
      frequent in older patients compared with younger patients. This is in contrast to
      the general guidelines for TDM where patients of advanced age are considered of
      particular importance to monitor closely.

PMID- 25565673
TI  - Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood
      Mononuclear Cells Correlate Well With Whole Blood Concentrations.
AB  - BACKGROUND: Everolimus (EVE) is an immunosuppressive drug dosed according to
      therapeutic drug monitoring in renal transplant recipients. The primary site of
      action is within activated lymphocytes. EVE is a substrate of the efflux
      transporter ABCB1 also known as P-glycoprotein. Limited data exist regarding a
      possible association between whole blood and intralymphocyte concentrations of
      EVE and the potential influence of ABCB1. METHODS: Twelve renal transplant
      recipients (5 men and 7 women) treated with EVE underwent a pharmacokinetic
      investigation where EVE concentrations in whole blood and in peripheral blood
      mononuclear cells (PBMC) were determined within a dosing interval. In addition,
      the activity of ABCB1 in PBMC was determined using the Rhodamine123 efflux assay
      and the patients' genotypes of ABCB1 were determined. RESULTS: There was a
      significant correlation between EVE AUC0-12 in whole blood and in PBMC (r = 0.90,
      P < 0.01), and no association was demonstrated between the ABCB1 activity and EVE
      PBMC/whole blood ratio of trough concentrations (r = 0.23, P = 0.76).
      Furthermore, ABCB1 1236C>T, 3435C>T, and 2677G>T/A polymorphism did not influence
      EVE AUC0-12 PBMC/whole blood ratio. CONCLUSIONS: The results revealed a
      significant association between EVE whole blood and PBMC concentrations,
      suggesting that ABCB1-mediated efflux from PBMC to be of minor importance for the
      distribution of EVE.

PMID- 25565674
TI  - Effect of CYP2B6*6 on Steady-State Serum Concentrations of Bupropion and
      Hydroxybupropion in Psychiatric Patients: A Study Based on Therapeutic Drug
      Monitoring Data.
AB  - BACKGROUND: The clinical effect of bupropion is mediated by its active metabolite
      hydroxybupropion. Previous studies have reported conflicting impact of the
      CYP2B6*6 variant allele on the formation of hydroxybupropion from bupropion. The
      aim of this study was to clarify the effect of CYP2B6*6 and secondarily CYP2D6
      genotype on steady-state serum concentrations of bupropion and hydroxybupropion
      in a large population of psychiatric patients. METHODS: Retrospective information
      about dose-adjusted serum concentrations (C/D ratios) of bupropion and
      hydroxybupropion, CYP2B6 genotype (ie, data on the 2B6*6 polymorphisms 516G>T and
      785A>G) and CYP2D6 genotype, was obtained from a therapeutic drug monitoring
      database (n = 132 patients). C/D ratios of bupropion and hydroxybupropion, and
      metabolic ratios, were compared between CYP2B6 genotype subgroups by multivariate
      mixed-model analyses (2B6*1/*1 was defined as control group). In the analyses,
      CYP2D6 genotype was also included as a covariate. RESULTS: Homozygous 2B6*6
      carriers (n = 7) had significantly lower C/D ratios of hydroxybupropion compared
      with controls (n = 79), that is, estimated mean 5.8 versus 13.0 nmol.L.mg (P <
      0.001). C/D ratio of hydroxybupropion in heterozygous *6 carriers (12.1
      nmol.L.mg; n = 46) did not significantly differ compared with controls (P =
      0.32). The hydroxybupropion/bupropion metabolic ratios in heterozygous and
      homozygous 2B6*6 carriers were significantly lower than in controls (P = 0.001
      and P < 0.001, respectively). CYP2D6 genotype did not significantly alter the
      hydroxybupropion C/D ratio, but higher bupropion values were observed in poor
      versus extensive CYP2D6 metabolizers (P = 0.020). CONCLUSIONS: This study shows
      that the CYP2B6*6 variant allele is associated with significantly reduced
      formation of the active bupropion metabolite in psychiatric patients. Our
      findings suggest that dose-adjusted serum concentrations of hydroxybupropion at
      steady state is approximately halved in homozygous CYP2B6*6 carriers, which might
      imply risk of reduced clinical response in this patient subgroup. The CYP2D6
      genotype does not affect hydroxybupropion concentrations and is therefore
      unlikely to impact bupropion treatment.

PMID- 25565675
TI  - Generation of an anti-Dabigatran Monoclonal Antibody and Its Use in a Highly
      Sensitive and Specific Enzyme-Linked Immunosorbent Assay for Serum Dabigatran.
AB  - BACKGROUND: Dabigatran (DT) is a direct thrombin inhibitor used to prevent venous
      and arterial thromboembolism due to atrial fibrillation. DT is the active form of
      the commercially available prodrug DT etexilate. Although DT has many clinical
      advantages over warfarin, it increases the incidence of bleeding in patients with
      renal dysfunction. Circulating levels of DT are increased in such patients
      because it is mainly eliminated by renal excretion. Therapeutic drug monitoring
      may therefore help to prevent adverse DT effects, but no method for measuring
      circulating DT levels has been reported, except for an analysis by liquid
      chromatography-tandem mass spectrometry. This study sought to develop a novel
      enzyme-linked immunosorbent assay (ELISA) to measure DT concentrations. METHODS:
      Mice were immunized with a DT-keyhole limpet hemocyanin conjugate to generate an
      anti-DT antibody. Immunized mouse splenocytes and myeloma cells (SP2/0) were
      fused to obtain an anti-DT monoclonal antibody (DT-mAb). DT-mAb and DT solutions
      were added to microplate wells coated with a DT-human serum albumin conjugate. DT
      concentrations were determined based on the principles of ELISA. RESULTS: DT-mAb
      was successfully purified from a hybridoma, and the competitive ELISA developed
      using this DT-mAb could evaluate DT concentrations ranging from 7.8 to 125 ng/mL.
      The ELISA signal was not linear using DT-spiked serum; however, it was linear
      when serum ultrafiltrate was used. Weak cross-reactivity with DT etexilate was
      detected, but no cross-reactivity was observed with other structurally related
      drugs or drugs commonly used for the treatment of atrial fibrillation.
      CONCLUSIONS: The developed competitive ELISA is a valuable and specific tool to
      analyze free DT in serum ultrafiltrate for therapeutic drug monitoring and
      pharmacokinetic studies.

PMID- 25565676
TI  - Some thoughts about patient ownership.

PMID- 25565678
TI  - A mobile app for securely capturing and transferring clinical images to the
      electronic health record: description and preliminary usability study.
AB  - BACKGROUND: Photographs are important tools to record, track, and communicate
      clinical findings. Mobile devices with high-resolution cameras are now
      ubiquitous, giving clinicians the opportunity to capture and share images from
      the bedside. However, secure and efficient ways to manage and share digital
      images are lacking. OBJECTIVE: The aim of this study is to describe the
      implementation of a secure application for capturing and storing clinical images
      in the electronic health record (EHR), and to describe initial user experiences.
      METHODS: We developed CliniCam, a secure Apple iOS (iPhone, iPad) application
      that allows for user authentication, patient selection, image capture, image
      annotation, and storage of images as a Portable Document Format (PDF) file in the
      EHR. We leveraged our organization's enterprise service-oriented architecture to
      transmit the image file from CliniCam to our enterprise clinical data repository.
      There is no permanent storage of protected health information on the mobile
      device. CliniCam also required connection to our organization's secure WiFi
      network. Resident physicians from emergency medicine, internal medicine, and
      dermatology used CliniCam in clinical practice for one month. They were then
      asked to complete a survey on their experience. We analyzed the survey results
      using descriptive statistics. RESULTS: Twenty-eight physicians participated and
      19/28 (68%) completed the survey. Of the respondents who used CliniCam, 89% found
      it useful or very useful for clinical practice and easy to use, and wanted to
      continue using the app. Respondents provided constructive feedback on location of
      the photos in the EHR, preferring to have photos embedded in (or linked to)
      clinical notes instead of storing them as separate PDFs within the EHR. Some
      users experienced difficulty with WiFi connectivity which was addressed by
      enhancing CliniCam to check for connectivity on launch. CONCLUSIONS: CliniCam was
      implemented successfully and found to be easy to use and useful for clinical
      practice. CliniCam is now available to all clinical users in our hospital,
      providing a secure and efficient way to capture clinical images and to insert
      them into the EHR. Future clinical image apps should more closely link clinical
      images and clinical documentation and consider enabling secure transmission over
      public WiFi or cellular networks.

PMID- 25565681
TI  - Important messages for clinical care and health policy on suicide.

PMID- 25565679
TI  - Multiobjective optimization strategy based on desirability functions used for the
      microemulsion liquid chromatographic separation and quantification of norfloxacin
      and tinidazole in plasma and formulations.
AB  - The aim of the present study was to optimize a microemulsion liquid
      chromatography method for the simultaneous determination of norfloxacin and
      tinidazole binary mixture using a chemometric protocol. Optimization experiments
      were conducted through a process of screening and optimization. A 2(7-4)
      fractional factorial design was used as screening design. While the location of
      optimum conditions was established by applying Derringer's desirability function.
      The optimal mobile phase composition was predicted to be: 3.5% w/v SDS, 10.03%
      v/v 1-propanol, 0.5% v/v 1-octanol, and 0.3% triethylamine in 0.02 M phosphoric
      acid at pH 6.5. The mobile phase was delivered isocratically at a flow rate of 1
      mL/min with UV detection at 290 nm. Tinidazole and norfloxacin were eluted with
      retention times of 1.8 and 5.8 min, respectively. The calibration plots displayed
      good linear relationships in the concentration ranges of 0.5-50 and 0.75-75
      MUg/mL for norfloxacin and tinidazole, respectively. The method was successfully
      applied for determination of both drugs in pharmaceutical dosage forms and real
      human plasma. Where the accuracy was proved by the low values of % error and high
      values of recovery, also the relative standard deviation for the results did not
      exceed 1.5%, proving the precision of the method.

PMID- 25565680
TI  - Text Messaging to Improve Hypertension Medication Adherence in African Americans:
      BPMED Intervention Development and Study Protocol.
AB  - BACKGROUND: Hypertension (HTN) is a major public health concern in the United
      States, with almost 78 million Americans age 20 years and over suffering from the
      condition. Moreover, HTN is a key risk factor for health disease and stroke.
      African Americans disproportionately shoulder the burdens of HTN, with greater
      prevalence, disease severity, earlier onset, and more HTN-related complications
      than age-matched whites. Medication adherence for the treatment of HTN is poor,
      with estimates indicating that only about half of hypertensive patients are
      adherent to prescribed medication regimens. Although no single intervention for
      improving medication adherence has emerged as superior to others, text message
      medication reminders have the potential to help improve medication adherence in
      African Americans with uncontrolled HTN as mobile phone adoption is very high in
      this population. OBJECTIVE: The purpose of this two-phased study was to develop
      (Phase I) and test in a randomized controlled trial (RCT) (Phase II) a text
      message system, BPMED, to improve the quality of medication management through
      increasing medication adherence in African Americans with uncontrolled HTN.
      METHODS: In Phase I, we recruited 16 target end-users from a primary care clinic,
      to assist in the development of BPMED through participating in one of three focus
      groups. Focus groups sought to gain patient perspectives on HTN, medication
      adherence, mobile phone use, and the use of text messaging to support medication
      adherence. Potential intervention designs were presented to participants, and
      feedback on the designs was solicited. In Phase II, we conducted two pilot RCTs
      to determine the feasibility, acceptability, and preliminary efficacy of BPMED in
      primary care and emergency department settings. Both pilot studies recruited
      approximately 60 participants, who were randomized equally between usual care and
      the BPMED intervention. RESULTS: Although data collection is now complete, data
      analysis from the two pilot RCTs is still ongoing and results are expected in
      2015. CONCLUSIONS: This study was designed to determine preliminary feasibility
      and acceptability of our approach among African Americans with uncontrolled HTN
      in primary care and emergency department settings. Results from these studies are
      of great interest as little work has been done to document the use of text
      message medication reminders to improve HTN-related outcomes, particularly within
      underserved urban minorities. TRIAL REGISTRATION: Clinicaltrials.gov NCT01465217;
      https://clinicaltrials.gov/ct2/show/NCT01465217 (Archived by WebCite at
      http://www.webcitation.org/6V0tto0lZ).

PMID- 25565682
TI  - How does untreated psychosis lead to neurological damage?

PMID- 25565677
TI  - Structural insight into effector proteins of Gram-negative bacterial pathogens
      that modulate the phosphoproteome of their host.
AB  - Invading pathogens manipulate cellular process of the host cell to establish a
      safe replicative niche. To this end they secrete a spectrum of proteins called
      effectors that modify cellular environment through a variety of mechanisms. One
      of the most important mechanisms is the manipulation of cellular signaling
      through modifications of the cellular phosphoproteome.
      Phosphorylation/dephosphorylation plays a pivotal role in eukaryotic cell
      signaling, with ~ 500 different kinases and ~ 130 phosphatases in the human
      genome. Pathogens affect the phosphoproteome either directly through the action
      of bacterial effectors, and/or indirectly through downstream effects of host
      proteins modified by the effectors. Here we review the current knowledge of the
      structure, catalytic mechanism and function of bacterial effectors that modify
      directly the phosphorylation state of host proteins. These effectors belong to
      four enzyme classes: kinases, phosphatases, phospholyases and serine/threonine
      acetylases.

PMID- 25565684
TI  - Are the effects of duration of untreated psychosis socially mediated?
AB  - Investigation of possible mechanisms by which longer duration of untreated
      psychosis (DUP) could influence treatment outcomes has focused primarily on
      evidence for neurotoxic effects. It is also possible that longer DUP has
      psychosocial effects, which could mediate its impact on outcomes. The evidence of
      relevance to such socially toxic effects is reviewed, with particular reference
      to the possible role of social support. There is no definite evidence for social
      support as a mediator of the influence of DUP, but further investigation of this
      issue is warranted. 

PMID- 25565683
TI  - The role of untreated psychosis in neurodegeneration: a review of hypothesized
      mechanisms of neurotoxicity in first-episode psychosis.
AB  - For over 20 years, studies have tried to measure the association between the
      duration of untreated psychosis (DUP) and changes in brain morphology. A
      hypothesis that untreated psychosis is neurotoxic has been postulated, but the
      mechanisms of that toxicity have not been described. We re-analyzed papers
      collected for a systematic review to extract data on the hypotheses that have
      been generated on the potential mechanisms by which DUP could impact brain
      morphology in first-episode psychosis. Dopaminergic hyperactivity, prolonged
      hypothalamic-pituitary-adrenal activation, and persistent activity of
      catecholamines have been hypothesized as mechanisms to explain these
      associations. However, the question remains as to whether the observed structural
      changes are permanent or may be reversed via antipsychotic treatment. 

PMID- 25565685
TI  - Service use and unmet needs in youth suicide: a study of trajectories.
AB  - OBJECTIVE: While 90% of suicide victims have suffered from mental health
      disorders, less than one-half are in contact with a mental health professional in
      the year preceding their death. Service use in the last year of life of young
      suicide victims and control subjects was studied in Quebec. We wanted to
      determine what kinds of health care services were needed and if they were
      actually received by suicide victims. METHOD: We recruited 67 consecutive suicide
      victims and 56 matched living control subjects (aged 25 years and younger). We
      evaluated subjects' psychopathological profile and determined which services
      would have been indicated by conducting a needs assessment. We then compared this
      with what services were actually received. RESULTS: Suicide victims were more
      likely than living control subjects to have a psychiatric diagnosis. They were
      most in need of services to address substance use disorder, depression,
      interpersonal distress, and suicide-related problems. There were significant
      deficits in the domains of coordination and continuity of care, mental health
      promotion and training, and governance. CONCLUSIONS: Our results show that we
      need to urgently take action to address these identified deficits to prevent
      further loss of life in our young people.

PMID- 25565686
TI  - Acute risk of suicide and suicide attempts associated with recent diagnosis of
      mental disorders: a population-based, propensity score-matched analysis.
AB  - OBJECTIVE: To determine the degree of risk during the first year after diagnosis
      with a mental illness. METHODS: We used propensity scoring to create a matched
      sample for all identified suicide attempts and suicide deaths in the province of
      Manitoba from 1996 to 2009. This study identified 2100 suicide deaths and 8641
      attempted suicides. Three control subjects were identified for every case and
      matched on age, sex, income decile, region of residence, and marital status. Five
      categories of physician-diagnosed mental disorders were tested: schizophrenia,
      anxiety, depression, dementia, and substance abuse. Logistic regression was used
      to determine the risk for suicide attempts and suicide deaths overall, and within
      3 time periods since initial diagnosis: 1 to 90 days, 91 to 364 days, and 365 or
      more days. RESULTS: All disorders, except dementia, were independently related to
      death. All disorders were related to suicide attempts. The risk of dying by
      suicide was particularly high within the first 90 days after initial diagnosis
      for many disorders, including depression (adjusted odds ratio [AOR] 7.33; 95% CI
      4.76 to 11.3), substance use disorders (AOR 4.07; 95% CI 2.43 to 6.82), and
      schizophrenia (AOR 20.91; 95% CI 2.55 to 172). Depression and anxiety disorders
      had elevated risk in the first year for suicide attempts. CONCLUSIONS: These data
      suggest that several mental disorders independently increase the risk of suicide
      attempts and death by suicide after controlling for all mental disorders and
      demographic risk factors. Clinicians should be aware of the heightened risk of
      suicide and suicidal behaviour within the first 3 months after initial diagnosis.

PMID- 25565687
TI  - Repetition of attempted suicide among immigrants in Europe.
AB  - OBJECTIVES: To compare frequencies of suicide attempt repetition in immigrants
      and local European populations, and the timing of repetition in these groups.
      METHOD: Data from 7 European countries, comprising 10 574 local and 3032
      immigrant subjects, were taken from the World Health Organization European
      Multicentre Study on Suicidal Behaviour and the ensuing Monitoring Suicidal
      Behaviour in Europe (commonly referred to as MONSUE) project. The relation
      between immigrant status and repetition of suicide attempt within 12-months
      following first registered attempt was analyzed with binary logistic regression,
      controlling for sex, age, and method of attempt. Timing of repetition was
      controlled for sex, age, and the recommended type of aftercare. RESULTS: Lower
      odds of repeating a suicide attempt were found in Eastern European (OR 0.50; 95%
      CI 0.41 to 0.61, P < 0.001) and non-European immigrants (OR 0.68; 95% CI 0.51 to
      0.90, P < 0.05), compared with the locals. Similar patterns were identified in
      the sex-specific analysis. Eastern European immigrants tended to repeat their
      attempt much later than locals (OR 0.58; 95% CI 0.35 to 0.93, P < 0.05). In
      general, 32% of all repetition occurred within 30 days. Repetition tended to
      decrease with age and was more likely in females using harder methods in their
      index attempt (OR 1.29; 95% CI 1.08 to 1.54, P < 0.01). Large variations in the
      general repetition frequency were identified between the collecting centres, thus
      influencing the results. CONCLUSIONS: The lower repetition frequencies in non
      Western immigrants, compared with locals, in Europe stands in contrast to their
      markedly higher tendency to attempt suicide in general, possibly pointing to
      situational stress factors related to their suicidal crisis that are less
      persistent over time. Our findings also raise the possibility that suicide
      attempters and repeaters constitute only partially overlapping populations.

PMID- 25565688
TI  - The 6-month prevalence of posttraumatic stress syndrome (PTSS) among older
      adults: validity and reliability of the PTSS scale.
AB  - OBJECTIVE: To document the 6-month prevalence of posttraumatic stress syndrome
      (PTSS) in the older adult population and the validity of a PTSS Scale in an
      epidemiologic setting. METHOD: Data came from the Enquete sur la sante des aines
      et l'utilisation des services de sante (ESA Services Study) conducted during 2012
      2013 using a probability sample of older adults seeking medical services in
      primary health clinics. RESULTS: Results showed that a first-order PTSS
      measurement model consisting of 3 indicators-the number of lifetime traumatic
      events, the frequency of reactions and symptoms of distress associated with the
      traumatic events, and the presence of consequences on the social functioning-was
      plausible. Reliability of the PTSS was 0.82. According to the PTSS, 11.1% of the
      older adult patients presented with PTSS, but only 21.7% of them reported an
      impact of their symptoms on their social functioning. The prevalence of older
      adults meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, criteria for full posttraumatic stress disorder (PTSD) reached 1.8%, and
      1.8% of older adults reached criteria for partial PTSD. Our results also showed
      that women were more at risk to report PTSS than men and that older adults aged
      75 years and older were less likely to report these symptoms than those aged
      between 65 and 74 years. CONCLUSIONS: PTSS is a common mental health problem
      among adults aged 65 and older and seeking health services in the general medical
      sector.

PMID- 25565689
TI  - Time trends in medically serious suicide-related behaviours in boys and girls.
AB  - OBJECTIVE: To determine whether emergency department (ED) presentations for
      suicide-related behaviours (SRBs) in boys and girls were identified as more
      clinically acute in the ED in the period after the regulatory warnings against
      prescribing antidepressants and during the global economic recession, and to
      characterize the medical severity of SRBs among boys and girls to aid
      surveillance activities. METHOD: Among Ontario boys and girls (aged 12 to 17
      years) presenting to the ED with an incident (index) ED SRB event between fiscal
      years (FYs) 2002 to 2010, we compared the number of high (compared with lower)
      acuity events in FYs 2005 to 2010 to those in FYs 2002 to 2004. We described the
      SRB method by its acuity and tested the linearity of varying trends in the SRB
      method in boys and girls. RESULTS: In both boys and girls, high acuity events
      were 50% greater after FY 2004 than before, regardless of subsequent admission,
      and most common among boys and girls who self-poisoned. In girls, opposing linear
      trends before and after FY 2004 were observed in the proportion of self
      poisonings and cut (or) pierce SRB methods. Throughout the study period, there
      was a linear decline in the proportion of boys presenting to the ED with other
      methods. CONCLUSIONS: The previously reported increase in hospital admissions
      after the warnings and during the recession is unlikely artifactual. An
      equivalent increase in high acuity events was also evident among those not
      subsequently admitted. The reasons for varying responses in boys and girls by SRB
      method warrant further study.

PMID- 25565690
TI  - An updated meta-analysis of randomized controlled evidence for the effectiveness
      of community treatment orders.
AB  - OBJECTIVES: It is unclear whether community treatment orders (CTOs) for people
      with severe mental illnesses can reduce health service use, or improve clinical
      and social outcomes. Randomized controlled trials of CTOs are rare because of
      ethical and logistical concerns. This meta-analysis updates available evidence.
      METHOD: A systematic literature search was performed of the Cochrane
      Schizophrenia Group Register, Science Citation Index, PubMed, MEDLINE, and Embase
      to November 2013. Inclusion criteria were studies comparing CTOs with standard
      care including those where control subjects received voluntary care, for most of
      the trial. RESULTS: Three studies provided 749 subjects for the meta-analysis.
      Two compared compulsory treatment with entirely voluntary care, while the third
      had control subjects receiving voluntary treatment for the bulk of the time.
      Compared with control subjects, CTOs did not reduce readmissions (risk ratio
      0.98, 95% CI 0.82 to 1.16) or bed days (mean difference [MD] -16.36; 95% CI -40.8
      to 8.05) in the subsequent 12 months (n = 749). Moreover, there were no
      significant differences in psychiatric symptoms (standardized MD -0.03; 95% CI 
      0.25 to 0.19; n = 331) or the Global Assessment of Functioning (MD -1.36; 95% CI 
      4.07 to 1.35; n = 335). Only including the 2 studies that compared compulsory
      treatment with entirely voluntary care made no difference to the results.
      CONCLUSIONS: CTOs may not lead to significant differences in readmission, social
      functioning, or symptomatology, compared with standard care. Their use should be
      kept under review.

PMID- 25565691
TI  - Suicide risk among active and retired Canadian soldiers: the role of
      posttraumatic stress disorder.

PMID- 25565693
TI  - Attention deficits and divorce.
AB  - OBJECTIVE: Building on previous work on the role of attention deficits associated
      with the regulation of executive control in psychiatric disorders, we examine
      whether these attention deficits are related to an interpersonal disturbance, the
      experience of divorce. METHOD: Attentional capacities of 95 randomly selected
      couples from the general population were measured with a well-established task,
      the Attentional Network Task, which assesses the efficiency of 3 attention
      networks (that is, alerting, orienting, and executive control). Among the 190
      participants, 32 had experienced a divorce in the past. ANCOVAs were used to
      compare divorced people in marital or cohabiting unions with people in first
      unions in their performance on this purely cognitive task. RESULTS: Our findings
      indicate that divorced people who are currently living in a cohabiting
      relationship show significantly lower executive control than other adults living
      as couples, after controlling for sex, age, income, and education. This subgroup
      of divorced people not only exhibit greater difficulty in responding to some
      stimuli while ignoring irrelevant ones but also manifest cognitive deficits in
      conflict resolution. CONCLUSIONS: This study highlights the links between
      attention and the long-term maintenance of intimate relationships. Our results
      may have important implications for the identification of people at risk for
      divorce.

PMID- 25565692
TI  - Posttraumatic stress disorder in adults: impact, comorbidity, risk factors, and
      treatment.
AB  - During the last 30 years, there has been a substantial increase in the study of
      posttraumatic stress disorder (PTSD). Several high-profile traumatic events, such
      as the wars in Afghanistan and Iraq, and the terrorist attacks of September 11 on
      the World Trade Center, have led to a greater public interest in the risk and
      protective factors for PTSD. In this In Review paper, I discuss some of the
      important advances in PTSD. The paper provides a concise review of the evolution
      of PTSD diagnosis in the Diagnostic and Statistical Manual of Mental Disorders,
      impact of PTSD in the community, an overview of the established risk factors for
      developing PTSD, and assessment and treatment. Throughout the paper,
      controversies and clinical implications are discussed. 

PMID- 25565694
TI  - Repetitive transcranial magnetic stimulation over the dorsolateral prefrontal
      cortex for treating posttraumatic stress disorder: an exploratory meta-analysis
      of randomized, double-blind and sham-controlled trials.
AB  - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) applied to the
      dorsolateral prefrontal cortex (DLPFC) has yielded promising results as a
      treatment for posttraumatic stress disorder (PTSD). However, to date, no
      quantitative review of its clinical utility has been published. METHOD: We
      searched for randomized and sham-controlled trials from 1995 to March 2013 using
      MEDLINE, Embase, PsycINFO, CENTRAL, and SCOPUS. We then performed an exploratory
      random effects meta-analysis. RESULTS: Studies on rTMS applied to the right DLPFC
      included 64 adults with PTSD. The pooled Hedges g effect size for pre and post
      changes in clinician-rated and self-reported PTSD symptoms were, respectively,
      1.65 (P < 0.001) and 1.91 (P < 0.001), indicating significant and large-sized
      differences in outcome favouring active rTMS. Also, there were significant pre
      and post decreases with active rTMS in overall anxiety (Hedges g = 1.24; P =
      0.02) and depressive (Hedges g = 0.85; P < 0.001) symptoms. Dropout rates at
      study end did not differ between active and sham rTMS groups. Regarding rTMS
      applied to the left DLPFC, there is only one study published to date (using a
      high frequency protocol), and its results showed that active rTMS seems to be
      superior overall to sham rTMS. CONCLUSIONS: Our exploratory meta-analysis shows
      that active rTMS applied to the DLPFC seems to be effective and acceptable for
      treating PTSD. However, the small number of subjects included in the analyses
      limits the generalizability of these findings. Future studies should include
      larger samples and deliver optimized stimulation parameters.

PMID- 25565697
TI  - Opening minds in Canada: targeting change.
AB  - OBJECTIVE: To summarize the ongoing activities of the Opening Minds (OM) Anti
      Stigma Initiative of the Mental Health Commission of Canada regarding the 4
      groups targeted (youth, health care providers, media, and workplaces), highlight
      some of the key methodological challenges, and review lessons learned. METHOD:
      The approach used by OM is rooted in community development philosophy, with
      clearly defined target groups, contact-based education as the central organizing
      element across interventions, and a strong evaluative component so that best
      practices can be identified, replicated, and disseminated. Contact-based
      education occurs when people who have experienced a mental illness share their
      personal story of recovery and hope. RESULTS: Results have been generally
      positive. Contact-based education has the capacity to reduce prejudicial
      attitudes and improve social acceptance of people with a mental illness across
      various target groups and sectors. Variations in program outcomes have
      contributed to our understanding of active ingredients. CONCLUSIONS: Contact
      based education has become a cornerstone of the OM approach to stigma reduction.
      A story of hope and recovery told by someone who has experienced a mental illness
      is powerful and engaging, and a critical ingredient in the fight against stigma.
      Building partnerships with existing community programs and promoting systematic
      evaluation using standardized approaches and instruments have contributed to our
      understanding of best practices in the field of anti-stigma programming. The next
      challenge will be to scale these up so that they may have a national impact.

PMID- 25565698
TI  - Key ingredients of anti-stigma programs for health care providers: a data
      synthesis of evaluative studies.
AB  - OBJECTIVE: As part of its ongoing effort to combat stigma against mental illness
      among health care providers, the Mental Health Commission of Canada partnered
      with organizations conducting anti-stigma interventions. Our objective was to
      evaluate program effectiveness and to better understand what makes some programs
      more effective than others. Our paper reports the elements of these programs
      found to be most strongly associated with favourable outcomes. METHODS: Our study
      employed a multi-phased, mixed-methods design. First, a grounded theory
      qualitative study was undertaken to identify key program elements. Next, each
      program (n = 22) was coded according to the presence or absence of the identified
      key program ingredients. Then, random-effects, meta-regression modelling was used
      to examine the association between program outcomes and the key ingredients.
      RESULTS: The qualitative analysis led to a 6-ingredient model of key program
      elements. Results of the quantitative analysis showed that programs that included
      all 6 of these ingredients performed significantly better than those that did
      not. Individual analyses of each of the 6 ingredients showed that including
      multiple forms of social contact and emphasizing recovery were characteristics of
      the most effective programs. CONCLUSIONS: The results provide a validation of a 6
      ingredient model of key program elements for anti-stigma programming for health
      care providers. Emphasizing recovery and including multiple types of social
      contact are of particular importance for maximizing the effectiveness of anti
      stigma programs for health care providers.

PMID- 25565699
TI  - Stigma in Canada: results from a rapid response survey.
AB  - OBJECTIVE: Our paper presents findings from the first population survey of stigma
      in Canada using a new measure of stigma. Empirical objectives are to provide a
      descriptive profile of Canadian's expectations that people will devalue and
      discriminate against someone with depression, and to explore the relation between
      experiences of being stigmatized in the year prior to the survey among people
      having been treated for a mental illness with a selected number of
      sociodemographic and mental health-related variables. METHOD: Data were collected
      by Statistics Canada using a rapid response format on a representative sample of
      Canadians (n = 10 389) during May and June of 2010. Public expectations of stigma
      and personal experiences of stigma in the subgroup receiving treatment for a
      mental illness were measured. RESULTS: Over one-half of the sample endorsed 1 or
      more of the devaluation discrimination items, indicating that they believed
      Canadians would stigmatize someone with depression. The item most frequently
      endorsed concerned employers not considering an application from someone who has
      had depression. Over one-third of people who had received treatment in the year
      prior to the survey reported discrimination in 1 or more life domains.
      Experiences of discrimination were strongly associated with perceptions that
      Canadians would devalue someone with depression, younger age (12 to 15 years),
      and self-reported poor general mental health. CONCLUSIONS: The Mental Health
      Experiences Module reflects an important partnership between 2 national
      organizations that will help Canada fulfill its monitoring obligations under the
      United Nations Convention on the Rights of Persons with Disabilities and provide
      a legacy to researchers and policy-makers who are interested in monitoring
      changes in stigma over time.

PMID- 25565695
TI  - The maternal adversity, vulnerability and neurodevelopment project: theory and
      methodology.
AB  - OBJECTIVE: To describe the theory and methodology of the multi-wave, prospective
      Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) study. The goal of
      MAVAN is to examine the pre- and postnatal influences, and their interaction, in
      determining individual differences in mental health. METHOD: MAVAN is a community
      based, birth cohort study of pregnant Canadian mothers and their offspring. Dyads
      are assessed longitudinally, with multiple assessments of both mother and child
      in home and laboratory across the child's development. Study measures, including
      assessments of cognitive and emotional function, are described. The study uses a
      candidate gene approach to examine gene-environment interdependence in specific
      developmental outcomes. Finally, the study includes measures of both brain-based
      phenotypes and metabolism to explore comorbidities associated with child obesity.
      One of the unique features of the MAVAN protocol is the extensive measures of the
      mother-child interaction. The relation between these measures will be discussed.
      RESULTS: Evidence from the MAVAN project shows interesting results about maternal
      care, families, and child outcomes. In our review, preliminary analyses showing
      the correlations between measures of maternal care are reported. As predicted,
      early evidence suggests that maternal care measures are positively correlated,
      over time. CONCLUSIONS: This review provides evidence for the feasibility and
      value of laboratory-based measures embedded within a longitudinal birth cohort
      study. Though retention of the samples has been a challenge of MAVAN, they are
      within a comparable range to other studies of this nature. Indeed, the trade-off
      of somewhat greater participant burden has allowed for a rich database. The
      results yielded from the MAVAN project will not only describe typical development
      but also possible targets for intervention. Understanding certain endophenotypes
      will shed light on the pathogenesis of various mental and physical disorders, as
      well as their interrelation.

PMID- 25565700
TI  - Report stigma is more life-limiting and disabling than the illness itself.

PMID- 25565701
TI  - When could a stigma program to address mental illness in the workplace break
      even?
AB  - OBJECTIVE: To explore basic requirements for a stigma program to produce
      sufficient savings to pay for itself (that is, break even). METHODS: A simple
      economic model was developed to compare reductions in total short-term disability
      (SDIS) cost relative to a stigma program's costs. A 2-way sensitivity analysis is
      used to illustrate conditions under which this break-even scenario occurs.
      RESULTS: Using estimates from the literature for the SDIS costs, this analysis
      shows that a stigma program can provide value added even if there is no reduction
      in the length of an SDIS leave. To break even, a stigma program with no reduction
      in the length of an SDIS leave would need to prevent at least 2.5 SDIS claims in
      an organization of 1000 workers. Similarly, a stigma program can break even with
      no reduction in the number of SDIS claims if it is able to reduce SDIS episodes
      by at least 7 days in an organization of 1000 employees. CONCLUSIONS: Modelling
      results, such as those presented in our paper, provide information to help
      occupational health payers become prudent buyers in the mental health market
      place. While in most cases, the required reductions seem modest, the real test of
      both the model and the program occurs once a stigma program is piloted and
      evaluated in a real-world setting.

PMID- 25565702
TI  - Opening minds in Canada.

PMID- 25565704
TI  - Listen to these lessons.

PMID- 25565705
TI  - Opening minds in Canada: background and rationale.
AB  - OBJECTIVE: To summarize the background and rationale of the approach taken by the
      Mental Health Commission of Canada's Opening Minds (OM) Anti-Stigma Initiative.
      METHOD: The approach taken by OM incorporates a grassroots, community development
      philosophy, has clearly defined target groups, uses contact-based education as
      the central organizing element across interventions, and has a strong evaluative
      component, so that best practices can be identified, replicated, and
      disseminated. Contact-based education occurs when people who have experienced a
      mental illness share their personal story of recovery and hope. RESULTS: OM has
      acted as a catalyst to develop partnerships between community groups who are
      undertaking anti-stigma work and an interdisciplinary team of academic
      researchers in 5 universities who are evaluating the results of these programs.
      CONCLUSIONS: Building partnerships with existing community programs and promoting
      systematic evaluation using standardized approaches and instruments have
      contributed to our understanding of best practices in the field of anti-stigma
      programming.

PMID- 25565707
TI  - Quantitative prediction of radio frequency induced local heating derived from
      measured magnetic field maps in magnetic resonance imaging: A phantom validation
      at 7 T.
AB  - Electrical Properties Tomography (EPT) technique utilizes measurable radio
      frequency (RF) coil induced magnetic fields (B1 fields) in a Magnetic Resonance
      Imaging (MRI) system to quantitatively reconstruct the local electrical
      properties (EP) of biological tissues. Information derived from the same data
      set, e.g., complex numbers of B1 distribution towards electric field calculation,
      can be used to estimate, on a subject-specific basis, local Specific Absorption
      Rate (SAR). SAR plays a significant role in RF pulse design for high-field MRI
      applications, where maximum local tissue heating remains one of the most
      constraining limits. The purpose of the present work is to investigate the
      feasibility of such B1-based local SAR estimation, expanding on previously
      proposed EPT approaches. To this end, B1 calibration was obtained in a gelatin
      phantom at 7 T with a multi-channel transmit coil, under a particular multi
      channel B1-shim setting (B1-shim I). Using this unique set of B1 calibration,
      local SAR distribution was subsequently predicted for B1-shim I, as well as for
      another B1-shim setting (B1-shim II), considering a specific set of parameter for
      a heating MRI protocol consisting of RF pulses plaid at 1% duty cycle. Local SAR
      results, which could not be directly measured with MRI, were subsequently
      converted into temperature change which in turn were validated against
      temperature changes measured by MRI Thermometry based on the proton chemical
      shift.

PMID- 25565708
TI  - Culling of invasive species--a comment.

PMID- 25565709
TI  - Dealing with new challenges: companion animal practice and the new economy.

PMID- 25565710
TI  - An ethicist's commentary on student veterinarians practicing without having a
      license.

PMID- 25565711
TI  - Retrospective evaluation of continuous rate infusion of regular insulin
      intravenously for the management of feline diabetic ketoacidosis.
AB  - The use and efficacy of continuous rate infusion (CRI) of regular insulin
      intravenously for the treatment of feline diabetic ketoacidosis was
      retrospectively evaluated. The study focused on the rate of glucose decline, time
      to resolution of inappetence, time to long-term injectable insulin, and length of
      hospital stay. Review of medical records from 2009 to 2011 identified 10 cases
      that met the inclusion criteria. Six cats were existing diabetics, 3 of whom had
      recent insulin changes. Five cats had concurrent diseases. The mean time to long
      term injectable insulin was 55 hours. The mean length of hospitalization was 3.8
      days. Five cats survived to discharge. In 5 patients, an insulin CRI permitted a
      short hospital stay and transition to long-term injectable insulin. Many cats
      with diabetic ketosis or diabetic ketoacidosis are prior diabetics with
      concurrent disease and/or a history of recent insulin changes. 

PMID- 25565712
TI  - Changes in blood pressure following escalating doses of phenylpropanolamine and a
      suggested protocol for monitoring.
AB  - This prospective, cross-over, blinded study evaluated the effect of various doses
      of phenylpropanolamine (PPA) on blood pressure in dogs. Dogs were randomized to
      receive a placebo or 1 of 3 dosages of immediate release PPA, q12h for 7 days [1
      mg/kg body weight (BW), 2 mg/kg BW, or 4 mg/kg BW] in a cross-over design. Blood
      pressure was recorded every 2 h, for 12 h, on days 1 and 7. There were
      significant increases in systolic, diastolic, and mean blood pressure following
      administration of PPA at 2 mg/kg BW and 4 mg/kg BW. A significant decrease in
      heart rate was also noted at all PPA dosages, but not in the placebo.
      Administration of PPA was associated with a dose response increase in blood
      pressure. Dosages of up to 2 mg/kg BW should be considered safe in healthy dogs. 

PMID- 25565713
TI  - Hypoadrenocorticism in a kindred of Pomeranian dogs.
AB  - Three adult Pomeranian dogs, full siblings from 2 litters, were diagnosed with
      primary hypoadrenocorticism following onset of hypoadrenal crisis. Review of the
      family history revealed the dogs' maternal grandmother also had
      hypoadrenocorticism. All 4 dogs were pedigree-certified by the American Kennel
      Club. An inherited basis for hypoadrenocorticism is proposed in these Pomeranian
      dogs. 

PMID- 25565714
TI  - Perianesthetic development of diaphragmatic hernia in a horse with equine
      pituitary pars intermedia dysfunction (PPID).
AB  - A 21-year-old Thoroughbred gelding with a history of equine pituitary pars
      intermedia dysfunction (PPID) presented with priapism of 2 days' duration. The
      horse received a caudal morphine epidural and then underwent corpus cavernosum
      lavage and phallectomy under general anesthesia. The patient's recovery featured
      multiple unsuccessful attempts to stand and his respiratory distress persisted
      for several hours until he acutely developed severe colic and was euthanized.
      Necropsy findings revealed a pituitary adenoma of the pars intermedia, bilateral
      adrenal cortical hyperplasia, and diaphragmatic herniation. This report suggests
      that horses with PPID may present a greater risk for diaphragmatic hernia under
      general anesthesia or during procedures placing stress on the diaphragm,
      including anesthetic recovery. 

PMID- 25565715
TI  - Prolonged survival of a cat diagnosed with feline infectious peritonitis by
      immunohistochemistry.
AB  - A 4-year-old, neutered male, British shorthair cat was presented with
      inappetence, vomiting, hyperproteinemia, and hyperglobulinemia. An exploratory
      celiotomy identified enlarged mesenteric lymph nodes. Immunohistochemistry of
      lymph node biopsies confirmed feline infectious peritonitis. This patient had a
      prolonged survival of 787 d after initial presentation. 

PMID- 25565716
TI  - Polioencephalomyelopathy in a mixed breed dog resembling Leigh's disease.
AB  - A 14-month-old mixed-breed dog was presented with acute onset of exercise
      intolerance that quickly progressed to quadriparesis. Gross and microscopic
      autopsy findings indicated a type of degenerative polioencephalomyelopathy
      resembling subacute necrotizing encephalomyelopathy in dogs or Leigh's disease in
      humans. This syndrome has previously been reported only in purebred dogs. 

PMID- 25565717
TI  - Mastitis in a neonatal filly.
AB  - Neonatal mastitis is a rare occurrence in the horse. This report documents a case
      of mastitis caused by an organism within the Streptococcus dysgalactiae group in
      a 1-week-old Paint filly. 

PMID- 25565718
TI  - Survey of Saskatchewan beef cattle producers regarding management practices and
      veterinary service usage.
AB  - Saskatchewan cow-calf producers (n = 2000) were surveyed to determine what
      factors were associated with their uptake of veterinary services; how and where
      they access nutritional information and animal health advice; and whether they
      were comfortable with having non-veterinarians perform veterinary procedures. The
      survey response rate was 18.1%. Veterinarians were seen as a primary source of
      nutritional information and animal health advice. Over the past decade producers
      have shifted their veterinary service usage from individual animal events to herd
      level procedures. Producers who pregnancy check were more likely to be large
      producers (OR = 1.9; 95% CI = 1.2 to 3.1; P = 0.007), to semen test their bulls
      (OR = 3.4; 95% CI = 2.0 to 5.8: P < 0.001), analyze their forages (OR = 2.3; 95%
      CI = 1.7 to 4.0; P = 0.006), and to farm in the brown versus the gray or dark
      brown soil zones (P = 0.004). Most (94.0%) respondents had adequate veterinary
      services within an hour's drive of the farm and 90.4% were satisfied with their
      veterinary service provider. Approximately 25% of respondents would be
      comfortable with having a non-veterinarian pregnancy check and attend to
      prolapses. 

PMID- 25565719
TI  - Total cystectomy and subsequent urinary diversion to the prepuce or vagina in
      dogs with transitional cell carcinoma of the trigone area: a report of 10 cases
      (2005-2011).
AB  - The cases of 10 dogs with transitional cell carcinoma of the urinary bladder that
      underwent total cystectomy were retrospectively reviewed to evaluate the
      feasibility and outcome of total cystectomy and ureteral transplantation to the
      prepuce or vagina. Dehiscence of ureterostomy (n = 2), pyelonephritis (n = 3),
      oliguria (n = 2), azotemia (n = 1), and ureteral obstruction (n = 1) were
      observed complications. The estimated median survival time was 385 days. This
      study demonstrates the feasibility of total cystectomy and subsequent urinary
      diversion to the prepuce or vagina in dogs. Compared to previous ureterocolonic
      anastomosis, this technique is associated with fewer gastrointestinal and
      neurologic complications. 

PMID- 25565720
TI  - Malignant catarrhal fever in a Red Angus cow.
AB  - A 3-year-old cow was presented with bilateral corneal edema, increased
      respiratory effort, nasal discharge, and pyrexia. Ovine herpesvirus-2 was
      detected, confirming malignant catarrhal fever (MCF). The findings from this case
      suggest that MCF should be included in the differential diagnosis of mature
      cattle with ocular and nasal lesions, especially when sheep are present on the
      farm. 

PMID- 25565721
TI  - Provincial ups and downs, national stagnation for associate veterinarians.

PMID- 25565722
TI  - Suicide in veterinary medicine: let's talk about it.

PMID- 25565723
TI  - Diagnostic ophthalmology. Complex corneal ulceration of the eye.

PMID- 25565724
TI  - Stereotactic radiation therapy in veterinary medicine.

PMID- 25565725
TI  - Design, fabrication, and properties of 2-2 connectivity cement/polymer based
      piezoelectric composites with varied piezoelectric phase distribution.
AB  - The laminated 2-2 connectivity cement/polymer based piezoelectric composites with
      varied piezoelectric phase distribution were fabricated by employing Lead
      Zirconium Titanate ceramic as active phase, and mixture of cement powder, epoxy
      resin, and hardener as matrix phase with a mass proportion of 4:4:1. The
      dielectric, piezoelectric, and electromechanical coupling properties of the
      composites were studied. The composites with large total volume fraction of
      piezoelectric phase have large piezoelectric strain constant and relative
      permittivity, and the piezoelectric and dielectric properties of the composites
      are independent of the dimensional variations of the piezoelectric ceramic layer.
      The composites with small total volume fraction of piezoelectric phase have large
      piezoelectric voltage constant, but also large dielectric loss. The composite
      with gradually increased dimension of piezoelectric ceramic layer has the
      smallest dielectric loss, and that with the gradually increased dimension of
      matrix layer has the largest piezoelectric voltage constant. The novel
      piezoelectric composites show potential applications in fabricating ultrasonic
      transducers with varied surface vibration amplitude of the transducer.

PMID- 25565726
TI  - Optical magnification: Need of the day.

PMID- 25565727
TI  - Oral hygiene awareness and practice amongst patients visiting the Department of
      Periodontology at a Dental College and Hospital in North India.
AB  - OBJECTIVE: This study was carried out to assess the oral hygiene awareness and
      practices amongst patients visiting the Department of Periodontology at Gian
      Sagar Dental College and Hospital, Ramnagar (Patiala). METHODS: A cross-sectional
      study was carried out amongst the patients visiting the Department of
      Periodontology of Gian Sagar Dental College and Hospital, Ramnagar, Patiala. This
      proposed study was reviewed by the Institutional ethical committee and their
      clearance was obtained. A total of 1000 patients were selected using a convenient
      sampling technique and a self-constructed questionnaire was presented to them.
      Responses from the patients were evaluated in terms of numbers and percentages
      and statistically also they were highly significant (P < 0.005). RESULTS: The
      results of the study show an acute lack of oral hygiene awareness and limited
      knowledge of oral hygiene practices as well as effect of poor oral hygiene on
      systemic health. CONCLUSION: There is an urgent need for comprehensive
      educational programs to promote good oral hygiene and impart education about
      correct oral hygiene practices.

PMID- 25565728
TI  - A clinical study of cysts of the maxillofacial region; and an assessment of
      clinico-radiologico-pathological variables affecting the formulation of a
      comprehensive patient need based treatment plan.
AB  - OBJECTIVES: Evaluation of clinical presentation of cystic lesions of the
      maxillofacial region, their relation to radiological picture, and treatment
      planning so as to plan and execute a patient need based treatment modality after
      co-relating it to the eventual histopathological diagnosis. METHODS: 25 cases
      with clinico-radiological diagnosis of a cyst were selected and treated, and the
      diagnosis was co-related to the eventual histopathological diagnosis. The
      patients were followed up for at least 3 months (3-12 months). An attempt was
      made to underline patient and lesion related variables having a bearing on the
      choice of treatment modality in each case. RESULTS: Out of 25 patients, 28% were
      females and 72% males. Commonly affected age groups were 11-20 (40%) and 31-40
      years (24%). 76% of 25 patients complained of swelling on the first visit. 96%
      lesions were related to jaws, of which 15 were in the mandible and 9 were in the
      maxilla. 58.33% bone lesions had cortical expansion. 92% lesions were confirmed
      to be cysts histopathologically. Two were ameloblastomas. 80% patients underwent
      enucleation with various adjunctive procedures. 32% patients faced temporary post
      operative complications. No recurrences were observed. Radiological presentation
      of lesions and patient's age were found to be the two most important radiological
      and clinical variables affecting treatment planning. CONCLUSIONS: A comprehensive
      patient need based treatment plan can be reached only after taking various
      patient and lesion related variables (which may manifest as clinical,
      radiological or histological parameters) into consideration.

PMID- 25565729
TI  - Impact of the quality of coronal restoration and root canal filling on the
      periapical health in adult syrian subpopulation.
AB  - BACKGROUND: The purpose of this study was to determine the status of periapical
      tissues of endodontically treated teeth according to coronal restorations and
      root canal fillings separately and in concomitant in adult Syrian subpopulation.
      METHODS: 784 endodontically treated teeth from two hundred randomly selected
      Syrian adult patients were radiographically evaluated. According to predetermined
      criteria, the quality of coronal restorations and root canal filling of each
      tooth was scored as adequate or inadequate. The status of periapical tissues was
      also classified as healthy or diseased. Results were analyzed using Chi-squared
      test. RESULTS: Adequate coronal restorations were determined in 58.54% of cases
      which was accompanied with less periapical pathosis than that in teeth with
      inadequate restorations (P < 0.01). 14% of teeth were restored by posts which
      showed no significant impact on the periapical tissues health. 18.5% of
      endodontic treatments were evaluated as adequate with less number of periapical
      radiolucencies than that of inadequate root canal fillings (P < 0.01). Absence of
      periapical pathosis was 96.6% in cases with both adequate coronal restorations
      and root canals fillings. The rate was 88.5% in cases with only adequate root
      canals fillings, and about 70% in cases with only adequate coronal restorations.
      When the treatment was inadequate in both coronal and root canals fillings,
      success rate was only observed in 48.8%. CONCLUSION: The most important factor
      with regard to the periradicular tissue health is the quality of root canal
      filling without neglecting the influence of coronal restoration (regardless of
      its type). There is a high prevalence rate of periapical pathosis in Syrian
      subpopulation due to poor dental practice.

PMID- 25565730
TI  - Serum vitamin c and iron levels in oral submucous fibrosis.
AB  - BACKGROUND: In this study Serum Vitamin C and Iron levels in Oral submucous
      fibrosis (OSMF) were estimated. The objective was to evaluate the correlation
      between Serum Vitamin C and Iron levels in OSMF individuals. Serum Iron content
      can be a predictor for the progression of this condition. OSMF is basically a
      disorder of collagen metabolism where Vitamin C gets utilized in conversion of
      proline into hydroxyproline, this hydroxylation reaction requires ferrous Iron
      and Vitamin C. Many studies regarding micronutrients and other antioxidants
      levels have been emphasized, but very few studies are done on the Serum levels of
      Vitamin C and its correlation with Iron in OSMF patients. METHODS: Thirty five
      OSMF patients and 50 deleterious habit free healthy individuals (controls) were
      selected. Two ml of venous blood was collected from each individual. Vitamin C
      level in serum was estimated by 2-4 dinitrophenylhydrazine method and Iron
      estimated by Tripyridyl method. RESULTS: The level of Serum Vitamin-C and Iron
      was significantly decreased in OSMF patients when compared to controls which were
      statistically significant. CONCLUSION: On the basis of these observations, it
      seems possible that the chemical, thermal and/or mechanical factors associated
      with the use of areca nut may act in conjunction with the Vitamin C and Iron
      deficiency leading to the development of OSMF. Therapeutic substitution of
      vitamin C and Iron may be recommended in the management of OSMF.

PMID- 25565731
TI  - Potential role of melatonin in prevention and treatment of oral carcinoma.
AB  - Melatonin, a hormone secreted mainly by pineal gland has been found to have
      antioxidant and anti-inflammatory properties in the oral cavity where it reaches
      through saliva. These properties have been found to be beneficial in certain oral
      pathologies including periodontal diseases, herpes viral infections and Candida,
      local inflammatory processes, xerostomia, oral ulcers and oral cancer. The
      objective of this review is to discuss the mechanism of action and potential role
      of melatonin as a preventive and curative agent for oral cancer. an extensive
      review of databases like pubmed, medline, science direct and Cochrane reviews was
      conducted to find articles related to beneficial actions of melatonin in human
      body with focus on cancers. Numerous studies both in-vitro and in-vivo had shown
      promising results regarding role of melatonin as anti-carcinogenic agent.
      Melatonin may play a role in protecting the oral cavity from tissue damage caused
      by oxidative stress. The experimental evidence suggests that melatonin may have
      utility in the treatment of several common cancers of the body. However, more
      specific studies are necessary to extend the therapeutic possibilities to oral
      carcinoma. 

PMID- 25565732
TI  - Report of a case with 19 supernumerary teeth in a non-syndromic patient.
AB  - Supernumerary teeth occur frequently in human dentition, but presence of multiple
      supernumerary teeth in patients without any associated syndrome or systemic
      disorder is a rare phenomenon. Presence of supernumerary teeth in itself is not a
      problem and may not require removal in all cases but in certain conditions, they
      may be associated with several clinical complications and require removal. Here,
      we present a 14 year old female who complained of non emergence of permanent
      teeth. Orthopantomogram initially showed presence of fifteen impacted
      supernumerary teeth distributed in all quadrants, but later, cone-beam computed
      tomography further revealed four additional teeth, totaling to nineteen
      supernumerary teeth. Consultation with concerned specialists ruled out any
      syndromes or systemic disorders which led us to the diagnosis of "non-syndromic
      multiple supernumerary teeth" and this probably is the highest number of
      supernumerary teeth reported in a single non-syndromic patient till date. 

PMID- 25565733
TI  - A case of Robinow-Sorauf syndrome (Craniosynostosis-Bifid Hallux Syndrome): The
      allelic variant of the Saethre-Chotzen syndrome.
AB  - The clinical classification of Robinow-Sorauf syndrome has changed over the last
      few decades. Robinow-Sorauf syndrome is characterized by facies similar to those
      of Saethre-Chotzen syndrome with bifid or partially duplicated halluces. The
      current outlook is that the 'Robinow-Sorauf' families are examples of variable
      expression of the TWIST mutant phenotype and that the 'Robinow-Sorauf' syndrome
      lies within the spectrum of the Saethre-Chotzen syndrome. We present a case of 19
      year-old female patient exhibiting classical clinical and radiological features
      of Robinow-Sorauf phenotype of Saethre-Chotzen syndrome. A brief review of
      previously reported cases and nosology has been presented. 

PMID- 25565734
TI  - Intramuscular hemangioma with phleboliths of the tongue.
AB  - Intramuscular hemangioma (IMH) is relatively rare benign tumor of vascular
      origin. Phleboliths are calcified thrombi found in the presence of hemangioma.
      The main treatment of the hemangioma is a surgical extirpation based on location,
      accessibility, and cosmetic considerations. We herein report a rare case of IMH
      with phleboliths of the tongue with clinical, imaging, and histopathological
      findings. 

PMID- 25565735
TI  - Esthetic and functional rehabilitation of mutilated dentition and loss of
      vertical dimension due to amelogenesis imperfecta.
AB  - Cases of severe attrition are a common finding. Among the congenital anomalies,
      amelogenesis imperfecta and dentinogenesis imperfecta are important conditions
      that may cause accelerated wear of teeth. The following case report describes the
      complete oral rehabilitation of a patient diagnosed with amelogenesis imperfecta.
      A detailed treatment plan was chalked out which included proper oral hygiene
      measures, restoration of carious teeth and endodontic treatment followed by
      foundation restorations of teeth that were crucial for the final prostheses.
      Patient was given transitional restorations for about 6 weeks with the aim of
      regaining the lost vertical dimensions. Final rehabilitation was done by fixed
      dental prostheses. 

PMID- 25565736
TI  - Karapandzic flap.
AB  - For full-thickness lip defects, the choice of reconstructive option depends on
      the size of the defect. Defects of one-quarter to one-third of the upper lip can
      be closed primarily. Largerdefects measuring one-third to two-thirds of the lower
      lip width may be closed with the Karapandzic, Abbe or Estlander flaps. If the
      commissure is involved, both the Karapandzic and Estlander flaps may be used;
      however, the Karapandzic is probably the better choice because it is better at
      maintaining oral competence. In the case of larger lower lip defects (more than
      two-thirds of the lip), if there is sufficient adjacent cheek tissue, the surgeon
      may employ the Karapandzic (for defects up to three-fourths of the lower lip
      width) or the Bernard-Burow's techniques (to reconstruct the entire lower lip). A
      case of post-traumatic, lower lip defect, reconstructed with a bilateral
      karapandzic flap is presented here. 

PMID- 25565737
TI  - Prosthodontic rehabilitation of patient with flabby ridges with different
      impression techniques.
AB  - A fibrous or flabby ridge is a superficial area of mobile soft tissue affecting
      the maxillary or mandibular alveolar ridges. It can develop when hyperplastic
      soft tissue replaces the alveolar bone and is a common finding particularly in
      the upper anterior region of long term denture wearers. Masticatory forces can
      displace this mobile denture-bearing tissue, leading to altered denture
      positioning and loss of peripheral seal. Forces exerted during the act of
      impression making can result in distortion of the mobile tissue. Unless managed
      appropriately by special impression techniques, such 'flabby ridges' adversely
      affect the support, retention and stability of complete dentures. This paper
      presents three case reports for prosthodontic rehabilitation of patient with
      flabby ridges with three different impression techniques. 

PMID- 25565738
TI  - Taking dentistry ahead.

PMID- 25565739
TI  - Effect of resin infiltration on the nanomechanical properties of demineralized
      bovine enamel.
AB  - OBJECTIVE: The aim of the present study was to evaluate the efficacy of resin
      infiltration in preventing in vitro lesion progression. MATERIALS AND METHODS:
      Buccal surfaces of bovine incisors were divided into mesial and distal regions
      and, at the center, nail varnish was applied (1.0 mm width) to protect the enamel
      surface against any further treatment. In order to create artificial enamel
      lesions in the unprotected areas, each specimen was soaked in a demineralizing
      solution. After that, specimens had two enamel lesions. One lesion in each sample
      was etched with 15% HCl for 120 s and infiltrated with a commercial infiltrating
      resin for 3 min, while the other lesion was not treated (control). Each specimen
      was cross-sectionally halved and randomly allocated to two groups: Group 1 was
      immediately processed and Group 2 was submitted to a new demineralization
      process. The samples were analyzed by means of cross-sectional hardness
      measurements using a nanoindenter equipment. Hardness data were statistically
      analyzed by non-parametric Kruskal-Wallis and MannWhitney tests (alpha = 0.05).
      RESULTS: The findings showed statistical difference between treatments at the
      same analyzed distance range from the outer surface of the enamel (P < 0.05).
      CONCLUSION: The untreated lesion showed lower hardness values for distances near
      the outer surface of the enamel. The resin infiltration was efficient in
      preventing further in vitro demineralization of bovine enamel lesions.

PMID- 25565740
TI  - Comparison of gonial angle determination from cephalograms and orthopantomogram.
AB  - INTRODUCTION: Gonial angle is an important parameter of the craniofacial complex
      giving an indication about the vertical parameters and symmetry of the facial
      skeleton. Both orthopantomogram (OPG) and lateral cephalograms can be used for
      the measurement of gonial angle. Because of the superimpositions seen on lateral
      cephalograms, reliable measurement of the gonial angle becomes difficult. The aim
      of the present study is to check the possible application and reliability of OPG
      for gonial angle determination by clarifying whether there is any significant
      difference between the determination of gonial angle from OPG and cephalogram.
      MATERIALS AND METHODS: Gonial angle measurements were made on lateral
      cephalograms and orthopantomograms of 98 patients - 44 males (mean age 25.9
      years) and 54 females (mean age 21.3 years), and compared using Statistical
      Package for Social Sciences. RESULTS: One-way analysis of variance demonstrated
      no significant differences between the values of gonial angles determined by
      lateral cephalogram and panoramic radiography. Pearson correlation showed a high
      correlation between cephalometric and OPG gonial angle value. CONCLUSION:
      Panoramic radiography can be used to determine the gonial angle as accurately as
      a lateral cephalogram. For determination of the gonial angle, an OPG may be a
      better choice than a lateral cephalogram as there are no interferences due to
      superimposed images of anatomical structures as in a lateral cephalogram. Thus,
      the present study substantiates the possibility of enhancing the clinical
      versatility of the panoramic radiograph, which is an indispensable tool for
      dental diagnosis.

PMID- 25565741
TI  - A microtensile bond strength evaluation of a single-bottle adhesive to caries
      affected dentin in conventional versus minimal invasive caries removal
      techniques: An in-vitro study.
AB  - BACKGROUND AND OBJECTIVE: The current dental restorative concepts are
      characterized by an increased effort towards a less invasive treatment of carious
      lesions. Minimally invasive cavity preparation techniques are intended to
      preserve as much sound enamel and dentin as possible, during the treatment of
      carious lesions. The objective of this in vitro study is to evaluate the
      microtensile bond strength of single-etch adhesives (Adper Easy one) on caries
      affected dentin, following three different caries removal techniques, namely,
      Carisolv, Conventional carbide bur at slow speed, and aqueous calcium hydroxide.
      MATERIALS AND METHODS: A total of 30 teeth were divided into three groups and
      arranged with 10 samples in each group - round bur (Group A), Carisolv (Group B),
      Aqueous calcium hydroxide (Group C). Following caries excavation by using the
      three above -mentioned techniques, application of the bonding agent and composite
      buildup was done. Following sectioning of the samples with the help of a hard
      tissue microtome, Group A, B, and C were again trimmed into an hour-glass shape,
      maintaining a width of 1.2 mm in the center of an hour glass. These were debonded
      under a microtensile load at failure, using the Instron Universal Testing
      Machine. RESULTS: There was a significantly lower microtensile bond strength in
      the group where the caries was removed by the round bur, as compared to the group
      where the caries was removed by using Carisolv and calcium hydroxide, which
      showed higher microtensile bond strength, that is, the significant pairing of
      Groups were Group A to Group B and Group A to Group C, exhibiting statistically
      significant difference with a P < 0.001. However, there was no statistically
      significant difference between Group B and Group C. INTERPRETATION AND
      CONCLUSION: Carisolv and aqueous calcium hydroxide have proven to be good methods
      of caries removal for achieving a higher microtensile bond strength of the single
      bottle self-etch adhesive on dentin.

PMID- 25565742
TI  - Evaluation of the efficacy of 100% Type-I collagen membrane of bovine origin in
      the treatment of human gingival recession: A clinical study.
AB  - BACKGROUND: Various treatment modalities have been devised for gingival
      recession, which is one of the most common signs of periodontal disease. The
      present study evaluates the efficacy of bioresorbable 100% type I collagen
      membrane of bovine origin in the treatment of human gingival recession. MATERIALS
      AND METHODS: Twenty cases of Miller's class I or class II localized gingival
      recession defects on the facial surface were treated with 100% type I collagen
      membrane of bovine origin in conjunction with coronally positioned flap. Pre
      operative and post-operative assessments were performed with respect to probing
      pocket depth, clinical attachment level and clinical recession at 12, 24 and 36
      weeks. The data thus collected were analyzed statistically. RESULTS:
      Statistically significant improvement based on Student's t test was found in all
      the three clinical parameters. CONCLUSION: Bioresorbable 100% type I collagen
      membrane of bovine origin has given inspiring results in the treatment of human
      gingival recession defects, thereby justifying the use of this material wherever
      indicated.

PMID- 25565743
TI  - The radiological versatility of fibrous dysplasia: An 8-year retrospective
      radiographic analysis in a north Indian population.
AB  - OBJECTIVE: The aim of this study was to examine the clinical and radiographic
      presentation of fibrous dysplasia through an 8-year retrospective study in
      patients who reported to the outpatient unit of the Kothiwal Dental College and
      Research Centre, Moradabad. MATERIALS AND METHODS: The clinical file records and
      radiographs of the patients who reported to the outpatient clinic in the
      Department of Oral Medicine and Radiology were retrospectively reviewed for
      histopathologically diagnosed fibrous dysplasia. A detailed analysis of the
      clinical and radiographic features of the 14 cases retrieved was carried out.
      RESULTS: Almost all the patients presented with a complaint of swelling on the
      side of the face. The maxilla was more frequently involved than the mandible. The
      most common radiographic pattern observed was the ground-glass appearance,
      followed by orange peel, cotton wool, sunray and thumb print appearance, which
      leads to a perplex differential diagnosis. CONCLUSION: Awareness of the versatile
      features of fibrous dysplasia evident through this study is essential in the
      accurate diagnosis and proper treatment planning of such lesions.

PMID- 25565744
TI  - Knowledge and awareness of the Consumer Protection Act among dental professionals
      in India: A systematic review.
AB  - BACKGROUND: The medical profession has been included in the Consumer Protection
      Act (CPA), to protect the interests of the patients in case of any unethical
      treatment rendered by the doctor. The present systematic review was conducted to
      assess the knowledge and awareness of CPA among dental professionals in India.
      MATERIALS AND METHODS: A systematic review of relevant cross-sectional
      observational studies was conducted regarding the level of knowledge and
      awareness of CPA among dental professionals in India. Five studies out of 44 were
      finally included in the present review, after conducting both an electronic and
      manual search of scientific databases. The potential biases were reported and
      appropriate data was extracted by the concerned investigators. RESULTS: More than
      90% of the study subjects in one of the studies were aware of the CPA, as
      compared to other studies. In two studies, when queried about the correct time
      period during which a patient can sue a doctor, very few subjects (18 and 23.2%)
      answered correctly. Almost 90% of the subjects were taking some form of consent
      in one of the studies. Private practitioners had more awareness as compared to
      academicians and combined practitioners. CONCLUSION: The results of the present
      review showed that a majority of the subjects were aware of the existence of CPA,
      but knowledge about the basic rules and regulations was lacking in a few studies.
      Therefore, dental professionals need to keep themselves updated on the various
      rules and latest amendments to save themselves from any litigation.

PMID- 25565746
TI  - Carcinoma ex pleomorphic adenoma: Diagnostic dilemma and treatment protocol.
AB  - Carcinoma ex pleomorphic adenoma (CXPA) is a carcinoma arising from a primary or
      recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to
      clinicians and pathologists. The entity is difficult to diagnose preoperatively.
      Pathological assessment is the gold standard for making the diagnosis. Treatment
      for CXPA often involves an ablative surgical procedure, which may be followed by
      radiotherapy. We report a case of a 65-year-old lady with a history of recurrent
      swelling in the left preauricular region and a history of surgery 10 years back,
      in the same region. Preoperatively, a diagnosis of pleomorphic adenoma of the
      parotid gland metastasizing to the cervical lymph node was made, but
      postoperatively it was reported as CXPA adenoma of the parotid gland. A radical
      parotidectomy involving en bloc resection of the facial nerve along with deep and
      superficial lobes of the parotid was performed followed by radiotherapy. The fact
      that pleomorphic adenomas are classified as benign tumors should not overshadow
      the wide range of biological behaviors associated with these tumors. On account
      of the potential for malignant transformation, surgical treatment must be
      properly performed. Surgery followed by radiotherapy should be considered as the
      standard care for a patient with carcinoma ex pleomorphic adenoma. 

PMID- 25565745
TI  - Endodontic management of maxillary first molar with seven root canals diagnosed
      using Cone Beam Computed Tomography scanning.
AB  - The main objective of root canal treatment is thorough cleaning and shaping of
      the entire pulp space and its complete filling with an inert filling material. A
      major cause of post-treatment disease is the inability to locate, debride or
      adequately fill all canals of the root canal system. The form, configuration, and
      number of root canals in the maxillary first molars have been discussed for more
      than half a century. Maxillary first molars commonly present with three roots and
      three canals, with a second mesiobuccal canal (MB2) also present. With the advent
      of improved magnification there are reports of multiple root canals in the
      maxillary first molars. Nonsurgical endodontic therapy of a left maxillary first
      molar with three roots and seven root canals was successfully performed under a
      dental operating microscope. The diagnosis of multiple root canals was confirmed
      with the help of Cone Beam Computed Tomography (CBCT) images. 

PMID- 25565747
TI  - Healing of a large periapical lesion using triple antibiotic paste and intracanal
      aspiration in nonsurgical endodontic retreatment.
AB  - A patient with a large periapical lesion in relation to the maxillary right
      central and lateral incisors is presented here. During the conservative root
      canal treatment, aspiration of the fluid was done through the root canal,
      followed by placement of triple antibiotic paste for two weeks. Complete
      periapical healing was observed at the 24-month recall. This report confirms that
      for treatment of a large periapical lesion it is not always necessary to do
      surgical treatment and even cyst-like periapical lesions heal following
      conservative endodontic therapy. 

PMID- 25565748
TI  - Segmental neurofibromatosis.
AB  - Segmental neurofibromatosis is a rare disorder, characterized by neurofibromas or
      cafiota-au-lait macules limited to one region of the body. Its occurrence on the
      face is extremely rare and only few cases of segmental neurofibromatosis over the
      face have been described so far. We present a case of segmental neurofibromatosis
      involving the buccal mucosa, tongue, cheek, ear, and neck on the right side of
      the face. 

PMID- 25565749
TI  - Dental Caries and the modern world.

PMID- 25565750
TI  - Mutations in the MSX1 gene in Turkish children with non-syndromic tooth agenesis
      and other dental anomalies.
AB  - AIM: To search for mutations on the MSX1 gene and to present a genetic basis for
      non-syndromic tooth agenesis in conjunction with dental anomalies in a Turkish
      population. MATERIALS AND METHODS: The patients included in this study were
      otherwise healthy, with ages ranging from seven to eighteen years. Eighty-two of
      them had one to six teeth missing (Group I) and 26 had more than six teeth
      missing (Group II), except for the third molars,. The missing teeth and dental
      anomalies were examined clinically and radiographically. The MSX1 gene was
      sequenced from the blood samples of patients who consented to the study. RESULTS:
      Mutations or polymorphisms on the MSX1 gene were identified in six patients.
      Taurodontism was seen in patients from both groups I and II. The nucleotide
      changes were identified by mutation screening. CONCLUSIONS: Performing family
      studies, screening other candidate genes, and investigation of interactions
      between genes will provide a basis for better analysis of tooth agenesis models
      and their association with other dental anomalies.

PMID- 25565752
TI  - Comparative evaluation of envelope type of advanced flap with and without type I
      collagen membrane (NEOMEMTM) in the treatment of multiple buccal gingival
      recession defects: A clinical study.
AB  - BACKGROUND: The aim of this study is to compare and evaluate the clinical outcome
      of the envelope-type of coronally advanced flap (CAF) alone versus envelope type
      of coronally advanced flap plus type I collagen membrane (NEOMEM) in the
      treatment of multiple buccal gingival recessions, using the split mouth study.
      MATERIALS AND METHODS: Ten patients in the age group of 20-50 years showing
      bilateral gingival recessions were treated. The defects in each patient were
      randomly assigned as Group A, which were treated with the envelope type of CAF,
      and those in Group B were treated with envelope type of CAF along with the Type I
      collagen membrane (NEOMEM). The recession depth (RD), probing depth (PD),
      clinical attachment level (CAL), and width of the keratinized tissue (KT) were
      measured at baseline, at three and six month intervals. RESULTS: Forty-six
      Miller's class I and II gingival recessions were treated. In the CAF + Type I
      collagen membrane (NEOMEM)-treated (Group B) sites the baseline gingival
      recession was 2.34 +/- 0.48 mm, while in the CAFtreated (Group A) sites it was
      2.52 +/- 0.84 mm. Both the treatments resulted in significant recession depth
      reduction (P < 0.001), but the reduction was significantly greater (P < 0.01) for
      Group B than Group A. The probing depth changes were significant (P < 0.01) for
      both groups, but the difference was nonsignificant. Similarly, a significant gain
      of CAL was seen in Group B (2.23 +/- 0.75 mm, P < 0.001) as well as in group A
      (1.60 +/- 0.86 mm, P < 0.001) showing a significant difference (P < 0.01) between
      the two groups. The width of keratinized tissue was also significantly (P <
      0.001) increased in both groups, but the increase was significantly greater (P <
      0.001) in group B (2.30 +/- 1.06 mm) than in group A (1.21 +/- 0.67 mm).
      CONCLUSION: The envelope type of CAF along with Type I collagen membrane (NEOMEM)
      was more effective than envelope type of CAF alone, in producing root coverage in
      multiple gingival recession defects, associated with gain in CAL as also in the
      width of KT.

PMID- 25565753
TI  - Evaluation of three different concentrations of Chlorhexidine for their
      substantivity to human dentin.
AB  - AIM: To evaluate the substantivity of different concentrations of Chlorhexidine
      (CHX) to dentin disks prepared in-vitro. MATERIALS AND METHODS: Sixty dentin
      disks were prepared from extracted human third molars and divided into three
      groups (each containing 20 disks). All the disks were partially demineralized, as
      per standard procedure. Group A specimens were then treated with 10 microliters
      of 0.02% Chlorhexidine, Group B specimens with 10 microliters of 0.2%
      Chlorhexidine, and Group C specimens were treated with 10 microliters of 2%
      Chlorhexidine. They were then incubated in 1 ml of Phosphatebufferedsaline PBS
      (pH 7.4). The substantivity was evaluated after 24 hours and one week of
      incubation. CHX concentration in the eluates was spectrophotometrically analyzed.
      RESULTS: A significant amount of CHX was found retained on the dentin disks in
      Group B as compared to Group C. Also, Group A performed significantly better than
      group C. However, no statistically significant difference was observed between
      Group A and Group B. CONCLUSION: Both 0.02% and 0.2% Chlorhexidine can be
      clinically recommended when being used for prolonging the durability of resin
      dentin bond.

PMID- 25565751
TI  - Evaluation of antimicrobial efficacy of garlic, tea tree oil, cetylpyridinium
      chloride, chlorhexidine, and ultraviolet sanitizing device in the decontamination
      of toothbrush.
AB  - OBJECTIVE: To assess and compare the efficacy of 3% garlic extract, 0.2% tea tree
      oil, 0.2% chlorhexidine, 0.05% cetylpyridinium chloride, and ultravoilet (UV)
      toothbrush sanitizing device as toothbrush disinfectants against Streptococcus
      mutans. MATERIALS AND METHODS: A double blind randomized controlled parallel
      study was done on 210 dental students. The subjects were divided into one control
      group using distilled water and five study groups representing 0.2% tea tree oil,
      3% garlic extract, 0.2% chlorhexidine gluconate, 0.05% cetylpyridinium chloride
      and UV toothbrush sanitizing device. Participants were provided with new
      toothbrushes and toothpastes for both baseline and intervention phases. The
      toothbrushes were collected after two weeks for microbial analysis in both
      phases. The data were analysed and compared using appropriate statistical
      analysis. RESULTS: On comparing pre- and post-intervention, S. mutans colony
      counts, a highly significant (P < 0.001) difference was observed in all the
      groups. Differences of 77.74 colony forming units (CFU) in tea tree oil group,
      102.87 CFU in garlic group, 68.13 CFU in chlorhexidine group, 82.47 CFU in
      cetylpyridinium group and 42.67 CFU in UV toothbrush sanitizer group were
      observed. Garlic group showed the highest reduction (100%) whereas UV toothbrush
      sanitizer group showed the least reduction (47.4%) in S. mutans colonies.
      CONCLUSIONS: The antimicrobial agents used in this study effectively reduced the
      S. mutans counts and hence can be considered as toothbrush disinfectants to
      prevent dental caries. The 3% garlic was the most effective among the
      antimicrobial agents.

PMID- 25565754
TI  - Perceptions of Indian dental hygiene students toward their profession and its
      relationship with their explicit self-esteem scores.
AB  - BACKGROUND: The purpose of this study was to investigate the perceptions toward
      the profession, the level of explicit self-esteem (ESE) of Indian students
      pursuing the course of dental hygienists, to evaluate the relationship between
      the two and to develop educational strategies to positively influence students'
      perceptions. We also wished to evaluate the level of satisfaction of the students
      to the current status of professional employment in the country. MATERIALS AND
      METHODS: Students in the second year of the dental hygienist 2-year course were
      asked to participate in a cross-sectional survey study. An instrument was used to
      obtain students' perceptions about the profession by estimating the dimensions of
      "Motivation," "Expectation" and "Environment". Their self-esteem was evaluated
      using the Rosenberg self-esteem scale. Relationship of self esteem scores with
      perceptions towards profession was then evaluated. RESULTS: Scores for dimensions
      including "Motivation," "Expectation" and "Environment" were significantly high,
      as were the self-esteem scores. The level of ESE was positively correlated with
      their perceptions of the profession. CONCLUSIONS: The perception of the Indian
      dental hygienist students was significantly high and positively correlated to the
      ESE scores. We also conclude that environmental factors may be more influential
      than innate cultural factors for the development of self-esteem.

PMID- 25565755
TI  - Squamous papilloma of the hard palate.
AB  - Oral squamous papillomas are benign proliferating lesions induced by human
      papilloma virus. These lesions are painless and slowly growing masses. As an oral
      lesion, it raises concern because of its clinical appearance. These lesions
      commonly occur between age 30 and 50 years, and sometimes can occur before the
      age of 10 years. Oral squamous papilloma accounts for 8% of all oral tumors in
      children. Common site predilection for the lesion is the tongue and soft palate,
      and may occur on any other surface of the oral cavity such as the uvula and
      vermilion of the lip. Here, we are presenting a case of squamous papilloma on the
      palate. 

PMID- 25565756
TI  - An aggressive odontogenic myxoma of the maxilla.
AB  - Odontogenic myxoma (OM) is a relatively rare benign odontogenic tumor of
      mesenchymal origin. OM is more common in the mandible than in the maxilla. It is
      an asymptomatic lesion that shows an infiltrative growth pattern. When the
      maxillary sinus is involved, it often fills the entire antrum. Odontogenic tumors
      are uncommon in the maxillary molar area, which often leads to diagnostic dilemma
      as this region of the maxilla is in the vicinity of vital structures, and
      radiographic overlapping of structures is always present. We present a similar
      case of a 17-year-old male patient who reported with a swelling in the left
      maxilla that infiltrated the maxillary sinus in a short duration of time. 

PMID- 25565757
TI  - Pycnodysostosis: A bone dysplasia with unusual oral manifestation.
AB  - Pycnodysostosis, a sclerosing bone dysplasia, is a rare autosomal recessive
      disorder with an estimated prevalence rate of one in one million. Patients with
      pycnodyostosis usually have normal intelligence, sexual development and life
      span. This condition is characterized by increased bone density and fragility
      along with oral manifestations like malposition teeth, hypoplastic maxilla,
      receded chin and delayed eruption of permanent teeth with discharging sinuses in
      the jaws because of poor blood supply. This is one such rare case report of a 47
      year-old patient presenting with a complaint of fractured jaw and reviewing the
      clinical and radiographic characteristics of pycnodysostosis. 

PMID- 25565758
TI  - Esthetic crown lengthening with depigmentation using an 810 nm GaAlAs diode
      laser.
AB  - Hyperpigmentation of gingiva becomes more pronounced if it is associated with
      "gummy smile." Correction of gummy smile and depigmentation together are key to
      complete patient satisfaction. An 810 nm (1.5 W, pulsed) GaAlAs diode laser was
      used to achieve the desired results in a 22-year-old female patient. The 6-month
      follow-up results showed excellent color and contour of the gingiva. Mere
      depigmentation without correcting gummy smile may look cosmetically good but
      esthetically unacceptable. Diode laser was used as it is known to be an excellent
      tool as compared with other conventional surgical procedures in terms of patient
      and operator comfort. 

PMID- 25565759
TI  - Extranodal large B-cell type aggressive non-Hodgkin's lymphoma.
AB  - Non-Hodgkin's lymphomas belong to a group of neoplasm originating from the cells
      of the lymphoreticular system that show diversity in their manner of
      presentation, response to therapy and prognosis. Non-Hodgkin's lymphoma accounts
      for 80-90% of all lymphomas. Although primary intraoral lesions in non-Hodgkin's
      lymphoma are uncommon, it is important to be aware of them as intraoral
      manifestations are a presenting symptom in these patients. A 72-year-old Indian
      male presented with a complaint of asymptomatic swelling in the left side of the
      face since 1.5 months. A careful clinical evaluation supported by radiologic,
      histopathologic and immunohistochemical investigations will help in identifying
      the disease at an early stage, which will result in better prognosis. 

PMID- 25565760
TI  - Mobility of Dissolved Organic Matter from the Suwannee River (Georgia, USA) in
      Sand-Packed Columns.
AB  - Transport of dissolved organic matter (DOM) from the Suwannee River and of
      synthetic polystyrene sulfonates (PSSs) was investigated in columns packed with
      naturally Fe/Al-oxide-coated sands from Oyster, Virginia. Surface-water samples
      were collected in May 2012 and processed by XAD-8 (humic substances; HPOA), XAD-4
      (transphilic acids [TPIAs]), and reverse osmosis (broad range of components;
      NOM). Median transport time (Ro ) of PSSs increased with molecular weight (MW)
      from 1,000 to 8,000 Da but decreased for the largest PSS (18,000 Da), which is
      consistent with previous observations of MW effects on DOM adsorption and
      transport. Breakthrough curves (BTCs) of HPOAs and NOM were similar whereas TPIA
      transport was distinct; although all DOM samples had similar Ro values, BTC
      asymmetry and dispersivity were greater for TPIAs. All samples exhibited power
      law tailing that is characteristic of heterogeneous sorbent/sorbate interactions,
      potentially including kinetic effects. The one-dimensional advection-dispersion
      equation was unable to capture the tailing but it was captured well using a
      continuous-time random walk (CTRW) model. CTRW parameters were similar for the
      NOM and HPOA samples but distinctly different for TPIAs, which had more
      pronounced tailing. While retardation of organics generally tends to increase
      with MW, the lower average MW of TPIAs did not result in decreased overall
      retardation, which suggests the importance of compositional differences. Results
      suggest that while TPIAs tend to be a relatively minor component of DOM, their
      transport behavior differs from that of the predominant HPOA fraction, and they
      might thus have different impacts on pollutant transport.

PMID- 25565761
TI  - 13C Nuclear Magnetic Resonance and Electron Paramagnetic Spectroscopic Comparison
      of Hydrophobic Acid, Transphilic Acid, and Reverse Osmosis May 2012 Isolates of
      Organic Matter from the Suwannee River.
AB  - Dissolved organic matter (DOM) is found in most natural waters at concentrations
      low enough to make DOM isolation methodologies critical to full analytical
      characterization and preservation. During the last few decades, two major
      protocols have been developed for the extraction of DOM isolates from natural
      waters. These methods utilize XAD resins and reverse osmosis (RO). In this work,
      the hydrophobic acid (May 2012 HPOA) and transphilic acid (May 2012 TPIA)
      isolates from XAD-8 and XAD-4 resins, respectively, were compared with the RO
      (May 2012 RO) natural organic matter isolate of the Suwannee River water using
      13C nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR)
      spectroscopies. 13C NMR analysis showed that the May 2012 RO isolate could be
      viewed as a hybrid of the more hydrophobic May 2012 HPOA isolate and more
      hydrophilic May 2012 TPIA isolate. The May 2012 HPOA isolate is shown to be
      higher in alkyl and aromatic moieties, while the May 2012 TPIA isolate is higher
      in O-alkyl moieties. EPR analysis revealed that the May 2012 TPIA and, in
      particular, May 2012 HPOA isolates had higher radical concentrations than the May
      2012 RO isolate. It is postulated that some of the radical concentrations came
      from the use of base during the isolation procedures, especially in the XAD
      method.

PMID- 25565762
TI  - Sentinel lymph node biopsy for conjunctival malignant melanoma: surgical
      techniques.
AB  - BACKGROUND: The purpose of this report is to examine the viability and safety of
      preoperative lymphoscintigraphy and radio guided sentinel lymph node (SLN) biopsy
      for conjunctival melanoma, and to identify the best technique to perform this
      procedure. METHODS: Three patients diagnosed with malignant melanoma of the
      conjunctiva underwent lymphoscintigraphy and SLN biopsy using a dual technique
      comprising isosulfan blue dye and technetium Tc 99m sulfur colloid. Each patient
      was anesthetized and the conjunctival melanoma was excised. SLNs were localized
      by a gamma probe, identified according to radioactivity and sentinel blue
      printing, and dissected, along with drainage of the associated lymphatic basins.
      The SLNs were evaluated by a pathologist using hematoxylin-eosin staining
      following serial sectioning and immunohistochemistry using a triple melanoma
      cocktail (S-100, Melan-A, and HMB-45 antigens). RESULTS: Two SLNs were stained in
      the jugular chain during preoperative lymphoscintigraphy in the first patient,
      two SLNs were identified in the preauricular and submandibular areas in the
      second patient, and two SLNs were identified in the submandibular and parotid
      areas in the third patient. All lymph nodes identified by lymphoscintigraphy were
      dissected and identified at surgery with 100% accuracy in all three patients. All
      SLNs were histologically and immunohistochemically negative. Patients had good
      cosmetic and functional results, and maintained their visual acuity and ocular
      motility. CONCLUSION: Patients with conjunctival melanoma can undergo
      preoperative lymphoscintigraphy and SLN biopsy safely using radioactive
      technetium and isosulfan blue dye.

PMID- 25565764
TI  - Intrapersonal comparison of initial axial length, keratometric readings, and
      intraocular lens power over a 6-month interval using an IOLMaster device.
AB  - PURPOSE: In order to improve current biometry practice, we investigated changes
      in axial length (AL), keratometry (K), and intraocular lens (IOL) power measured
      by the IOLMaster in adults within a 6-month period at the outpatient eye clinic,
      King Chulalongkorn Memorial Hospital, Bangkok, Thailand. PATIENTS AND METHODS:
      This was a nonrandomized prospective cohort study. The AL, steepest K, flattest
      K, and IOL power of nondilated eyes were measured at the initial examination and
      later at 6 months by the IOLMaster. Changes in AL, K, and IOL power using the SRK
      (Sanders, Retzlaff, and Kraff)-T formula within 6 months were compared using the
      paired-sample t-test. RESULTS: The study comprised 90 eyes from 90 patients. The
      mean age of the patients was 62.99+/-13.95 years (range 28-87 years). Mean values
      and standard deviation for AL, steepest K, flattest K, and IOL power at initial
      visit and 6 months later were 23.56+/-1.51 mm and 23.56+/-1.52 mm (P=1.0; 95%
      confidence interval [CI] -0.01 to 0), 44.94+/-1.37 D and 44.98+/-1.43 D (P=0.96;
      95% CI -0.13 to 0.04), 43.85+/-1.43 D and 43.89+/-1.36 D (P=0.93; 95% CI -0.02 to
      0.07), and 20.27+/-4.12 D and 20.15+/-4.51 D (P=0.99; 95% CI -0.05 to 0.29),
      respectively. CONCLUSION: There was no statistically significant difference in AL
      (P=1.0), both K (P=0.96, P=0.93), or IOL power (P=0.99) within the 6-month period
      using the IOLMaster. Remeasurement at 6 months may be required in some cases, but
      should not be routine.

PMID- 25565763
TI  - Quality of life following glaucoma surgery: canaloplasty versus trabeculectomy.
AB  - PURPOSE: To evaluate quality of life (QoL) with a new questionnaire after
      canaloplasty (CP) and trabeculectomy (TE). PATIENTS AND METHODS: We assessed
      outcomes of surgery, rate of revision surgeries, patients' mood, and influence of
      postoperative care on QoL, surgery interference with daily activities, and
      postsurgical complaints. Patients completed the QoL questionnaire 24 months after
      surgery. RESULTS: Patients who underwent CP (n=175) were compared to TE patients
      (n=152). In the CP group, 57% of patients expressed high satisfaction, while 41%
      of patients in the TE group said they were highly satisfied. The satisfaction
      difference was statistically significant (P=0.034). Significantly fewer second
      surgeries were needed after CP (8% CP versus 35% TE, P<0.001). Patients were more
      positive in the CP group (54% CP versus 37% TE, P<0.009). Stress related to
      postoperative care was lower in the CP group compared to the TE group (14% versus
      46%). Difficulties with activities of daily living, such as reading, were much
      lower or even nonexistent after CP, and complaints like eye burning or stinging
      were significantly lower in the CP group. CONCLUSIONS: Compared with TE, CP is
      associated with less QoL impairment and higher patient satisfaction after
      surgery. However, long-term data on intraocular pressure reduction after surgery
      are needed to confirm long-term patient satisfaction with this surgery.

PMID- 25565765
TI  - Bilateral lid/brow elevation procedure for severe ptosis in Kearns-Sayre
      syndrome, a mitochondrial cytopathy.
AB  - BACKGROUND: The purpose of this work was to determine the effectiveness and
      possible complications encountered with bilateral fascia lata lid suspension used
      to correct blepharoptosis in patients with Kearns-Sayre syndrome. METHODS: This
      was a retrospective study of seven patients with Kearns-Sayre syndrome who had a
      minimum of 1 year of follow-up. A bilateral fascia lata sling was used to correct
      the ptosis. Preoperative and postoperative measurements of the vertical lid
      fissure width (VFW) and marginal reflex distance (MRD) were performed. The
      Student's t-test was used to analyze the results. RESULTS: The mean preoperative
      VFW and MRD measurements were 4+/-2.45 mm and 0.14+/-0.92 mm, respectively. The
      mean postoperative VFW and MRD measurements were 7.71+/-1.85 mm, and 2.86+/-1.69
      mm, respectively. All preoperative and postoperative values were considered to be
      statistically significant (P<0.01). Adequate elevation of the lids was obtained
      in all patients, both functionally and aesthetically. All of the patients showed
      a mild symmetric postoperative inferior version lagophthalmos, and one patient
      developed corneal ulceration and scarring due to corneal exposure and a weak
      Bell's phenomenon. CONCLUSION: The surgical technique described to correct the
      blepharoptosis found in patients with Kearns-Sayre syndrome was found to be
      efficient and relatively safe. The correction should be conservative to decrease
      the risk of postoperative corneal damage that occurred in one patient.

PMID- 25565766
TI  - Single-step transepithelial ASLA (SCHWIND) with mitomycin-C for the correction of
      high myopia: long term follow-up.
AB  - PURPOSE: We wanted to compare the outcomes of single-step modified
      transepithelial photorefractive keratectomy (tPRK) termed a SCHWIND all surface
      laser ablation (ASLA) versus conventional alcohol-assisted photorefractive
      keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) for the
      correction of higher myopia of 6.00 diopters (D) or more, in an area with high
      risk of haze due to high intensity of sunlight. METHODS: We used a prospective
      interventional cohort with matched retrospective control groups. Patients with >6
      D myopia and <3.5 D of astigmatism were included. All treatments were performed
      with the SCHWIND Amaris system using aspheric ablation profiles. Mitomycin C was
      used in all PRK and ASLA cases. Outcomes were postoperative refraction, visual
      acuity, stability, and complications. The follow-up period was up to 12 months.
      RESULTS: In total, 101 eyes were included after exclusions. Mean preoperative
      spherical equivalent refraction was -7.9 D, -8.2 D, and -7.4 D in the ASLA
      (n=41), PRK (n=29), and LASIK (n=31) groups. Mean postoperative spherical
      equivalent at 12 months postoperatively was -0.1 (standard deviation [SD]: 0.34),
      -0.2 (SD: 0.59), and -0.08 (SD: 0.36) in the ASLA, PRK, and LASIK groups, with
      91.4%, 85.7%, and 83.9% within 0.5 D of target, respectively. Refractive outcomes
      and regression at 12 months did not vary among groups (P>0.05). Mean logMAR
      (logarithm of the minimum angle of resolution) uncorrected distance visual acuity
      at 12 months was 0.00 (SD: 0.05), 0.06 (SD: 0.1), and 0.05 (SD: 0.09) in the
      ASLA, PRK, and LASIK groups, with significantly better vision in the tPRK group
      versus LASIK (P=0.01) and PRK (P=0.01) groups. CONCLUSION: ASLA (SCHWIND) tPRK
      with mitomycin C for high myopia demonstrates comparable refractive outcomes to
      LASIK and PRK, with relatively favorable visual acuity outcomes. There was no
      increased incidence of haze in the ASLA group.

PMID- 25565767
TI  - Isolated posterior uveal effusion: expanding the spectrum of the uveal effusion
      syndrome.
AB  - Uveal effusion syndrome usually causes peripheral chorioretinal detachment, but
      posterior effusion may present as isolated macular edema with serous macular
      detachment in the setting of hyperopia and a thickened posterior choroid.
      Carbonic anhydrase inhibitors may be effective to treat this condition. 

PMID- 25565768
TI  - Prostaglandin-associated periorbitopathy in latanoprost users.
AB  - PURPOSE: We investigated the incidence of prostaglandin-associated
      periorbitopathy (PAP) in subjects with glaucoma treated with latanoprost
      ophthalmic solution. SUBJECTS AND METHODS: One eye and the forehead in 22
      subjects were evaluated. All patients had used latanoprost for more than 1 year
      (range, 12 to 45 months; mean, 26.0 months) and were prostaglandin F2alpha
      analogue treatment-naive. Digital photographs of the subjects obtained before
      latanoprost therapy and at the last examination were compared retrospectively.
      Four signs of PAP (deepening of the upper eyelid sulcus (DUES), upper eyelid
      ptosis, flattening of the lower eyelid bags, and inferior scleral show) and
      supplemental side effects around the eyelids (eyelash growth, poliosis, and
      eyelid pigmentation) were judged to be negative or positive by three independent
      observers. If the observers unanimously rated a sign as positive, the result was
      defined as positive. RESULTS: Twelve subjects (54.5%) had no apparent signs.
      Three subjects were judged to have DUES (13.6%), and two subjects each were
      judged to have flattening of the lower eyelid bags and eyelid pigmentation
      (9.0%). The other signs were judged as positive in only one subject each,
      respectively (4.5%). A univariate logistic regression analysis showed no
      significant associations between any of the signs and age, sex, or the duration
      of therapy. CONCLUSION: Latanoprost induced DUES, upper eyelid ptosis, flattening
      of the lower eyelid bags, inferior scleral show, and supplemental side effects
      around the eyelids; however, the rates of such occurrence might be relatively
      low.

PMID- 25565769
TI  - Impact of crystal polymorphism on the systemic bioavailability of rifaximin, an
      antibiotic acting locally in the gastrointestinal tract, in healthy volunteers.
AB  - BACKGROUND: Rifaximin is an antibiotic, acting locally in the gastrointestinal
      tract, which may exist in different crystal as well as amorphous forms. The
      current marketed rifaximin formulation contains polymorph alpha, the systemic
      bioavailability of which is very limited. This study compared the
      pharmacokinetics of this formulation with those of the amorphous form. METHODS:
      Amorphous rifaximin was specifically prepared for the study and formulated as the
      marketed product. Two doses (200 mg and 400 mg) of both formulations were given
      to two groups of 12 healthy volunteers of either sex according to a single-blind,
      randomized, two-treatment, single-dose, two-period, cross-over design. Plasma and
      urine samples were collected at preset times (for 24 hours or 48 hours,
      respectively) after dosing, and assayed for rifaximin concentrations by high
      performance liquid chromatography-mass spectrometry. RESULTS: For both dose
      levels, peak plasma concentration, area under the concentration-time curve, and
      cumulative urinary excretion were significantly higher after administration of
      amorphous rifaximin than rifaximin-alpha. Ninety percent confidence intervals for
      peak plasma concentration, area under the concentration-time curve, and urinary
      excretion ratios were largely outside the upper limit of the accepted (0.80-1.25)
      range, indicating higher systemic bioavailability of the amorphous rifaximin. The
      few adverse events recorded were not serious and not related to the study
      medications. CONCLUSION: Rifaximin-alpha, a crystal polymorph, does differ from
      the amorphous form, the latter being systemically more bioavailable. In this
      regard, care must be taken when using - as a medicinal product - a formulation
      containing even small amounts of amorphous form, which may alter the peculiar
      pharmacologic properties of this poorly absorbed antibiotic.

PMID- 25565770
TI  - Microemulsion of babassu oil as a natural product to improve human immune system
      function.
AB  - BACKGROUND: The aim of this study was to develop and characterize a babassu oil
      microemulsion system and determine the effect of this microemulsion on the
      functional activity of phagocytes. METHODS: The microemulsion was formulated
      using distilled water, babassu as the oil phase component, Sorbitan monooleate
      Span 80((r)) (SP), Polysorbate 80-Tween 80((r)) (TW), and 1-butanol (BT).
      Pseudoternary diagrams were prepared, and microemulsion diagram regions were
      preselected. Rheological characterization and preliminary and accelerated
      stability tests were performed. The effect of the microemulsion on the
      interactions between leukocytes and bacteria was determined by superoxide
      release, phagocytosis, and microbicidal activity. RESULTS: The developed
      formulation SP/TW/BT (4.2/4.8/1.0) was classified as oil/water, showed a
      Newtonian profile, and had linear viscosity. When we assessed the interaction of
      the microemulsion or babassu oil with phagocytes, we observed an increase in
      superoxide, phagocytosis, and microbicidal activity. CONCLUSION: The babassu oil
      microemulsion system is an option for future applications, including for vaccine
      delivery systems. Babassu oil is a natural product, so is an alternative for
      future immunotherapy strategies, in particular for infectious diseases.

PMID- 25565771
TI  - Arsenic sulfide, the main component of realgar, a traditional Chinese medicine,
      induces apoptosis of gastric cancer cells in vitro and in vivo.
AB  - BACKGROUND: Arsenic sulfide (As4S4), the main component of realgar, a traditional
      Chinese medicine, has shown antitumor efficacy in several tumor types, especially
      for acute promyelocytic leukemia. In this study, we aimed to explore the efficacy
      and mechanism of As4S4 in gastric cancer. METHODS: The effect of As4S4 on cell
      proliferation and apoptosis of gastric cancer cells was investigated by MTT
      assay, 4',6-diamidino-2-phenylindole (DAPI) staining, and annexin V-fluorescein
      isothiocyanate/propidium iodide staining using gastric cancer cell lines AGS
      (harboring wild-type p53) and MGC803 (harboring mutant p53) in vitro. The
      expression of apoptosis-related proteins was measured by Western blotting, real
      time polymerase chain reaction, and immunohistochemistry analysis. Mouse
      xenograft models were established by inoculation with MGC803 cells, and the
      morphology and the proportion of apoptotic cells in tumor tissues were detected
      by hematoxylin and eosin staining and TdT-mediated dUTP nick end labeling (TUNEL)
      assay, respectively. RESULTS: As4S4 inhibited the proliferation and induced
      apoptosis of AGS and MGC803 cells in a time- and dose-dependent manner. As4S4
      upregulated the expression of Bax and MDM2 while downregulated the expression of
      Bcl-2. The expression of p53 increased significantly in the AGS cells but did not
      readily increase in the MGC803 cells, which harbored mutant p53. Pifithrin-alpha,
      a p53 inhibitor, blocked the modulation of As4S4 on AGS cells, but not on MGC803
      cells. Using xenograft as a model, we showed that As4S4 suppressed tumor growth
      and induced apoptosis in vivo and that the expression of p53 increased
      accordingly. CONCLUSION: As4S4 is a potent cytotoxic agent for gastric cancer
      cells, as it induced apoptosis both in vitro and in vivo through a p53-dependent
      pathway. Our data indicate that As4S4 may have therapeutic potential in gastric
      cancer.

PMID- 25565772
TI  - Glycyrrhetinic acid and E.resveratroloside act as potential plant derived
      compounds against dopamine receptor D3 for Parkinson's disease: a
      pharmacoinformatics study.
AB  - Parkinson's disease (PD) is caused by loss in nigrostriatal dopaminergic neurons
      and is ranked as the second most common neurodegenerative disorder. Dopamine
      receptor D3 is considered as a potential target in drug development against PD
      because of its lesser side effects and higher degree of neuro-protection. One of
      the prominent therapies currently available for PD is the use of dopamine
      agonists which mimic the natural action of dopamine in the brain and stimulate
      dopamine receptors directly. Unfortunately, use of these pharmacological
      therapies such as bromocriptine, apomorphine, and ropinirole provides only
      temporary relief of the disease symptoms and is frequently linked with insomnia,
      anxiety, depression, and agitation. Thus, there is a need for an alternative
      treatment that not only hinders neurodegeneration, but also has few or no side
      effects. Since the past decade, much attention has been given to exploitation of
      phytochemicals and their use in alternative medicine research. This is because
      plants are a cheap, indispensable, and never ending resource of active compounds
      that are beneficial against various diseases. In the current study, 40 active
      phytochemicals against PD were selected through literature survey. These ligands
      were docked with dopamine receptor D3 using AutoDock and AutoDockVina. Binding
      energies were compared to docking results of drugs approved by the US Food and
      Drug Administration against PD. The compounds were further analyzed for their
      absorption, distribution, metabolism, and excretion-toxicity profile. From the
      study it is concluded that glycyrrhetinic acid and E.resveratroloside are potent
      compounds having high binding energies which should be considered as potential
      lead compounds for drug development against PD. 

PMID- 25565773
TI  - Postsynaptic density protein 95-regulated NR2B tyrosine phosphorylation and
      interactions of Fyn with NR2B in levodopa-induced dyskinesia rat models.
AB  - CONTEXT: Abnormality in interactions between N-methyl-d-aspartate (NMDA) receptor
      and its signaling molecules occurs in the lesioned striatum in Parkinson's
      disease (PD) and levodopa-induced dyskinesia (LID). It was reported that Fyn
      mediated NR2B tyrosine phosphorylation, can enhance NMDA receptor function.
      Postsynaptic density protein 95 (PSD-95), one of the synapse-associated proteins,
      regulates interactions between receptor and downstream-signaling molecules. In
      light of the relationship between PSD-95, NR2B, and Fyn kinases, does PSD-95
      contribute to the overactivity of NMDA receptor function induced by dopaminergic
      treatment? To further prove the possibility, the effects of regulating the PSD-95
      expression on the augmented NR2B tyrosine phosphorylation and on the interactions
      of Fyn and NR2B in LID rat models were evaluated. METHODS: In the present study,
      parkinsonian rat models were established by injecting 6-hydroxydopamine.
      Subsequently, valid PD rats were treated with levodopa (50 mg/kg/day with
      benserazide 12.5 mg/kg/day, twice daily) intraperitoneally for 22 days to create
      LID rat models. Then, the effect of pretreatment with an intrastriatal injection
      of the PSD-95mRNA antisense oligonucleotides (PSD-95 ASO) on the rotational
      response to levodopa challenge was assessed. The effects of pretreatment with an
      intrastriatal injection of PSD-95 ASO on the augmented NR2B tyrosine
      phosphorylation and interactions of Fyn with NR2B in the LID rat models were
      detected by immunoblotting and immunoprecipitation. RESULTS: Levodopa
      administration twice daily for 22 days to parkinsonian rats shortened the
      rotational duration and increased the peak turning responses. The altered
      rotational responses were attenuated by PSD-95 ASO pretreatment. Meanwhile, PSD
      95 ASO pretreatment decreased the level of PSD-95 protein expression and reduced
      both the augmented NR2B tyrosine phosphorylation and interactions of Fyn with
      NR2B triggered during the levodopa administration in the lesioned striatum of PD
      rats. However, the protein levels of Fyn and NR2B showed no difference under the
      above conditions. CONCLUSION: The data demonstrate that the inhibition of PSD-95
      protein expression suppressed the interactions of Fyn with NR2B and NR2B tyrosine
      phosphorylation and subsequently downregulated NMDA receptor overactivation, thus
      providing benefit for the therapy of LID. Therefore, PSD-95 is important for
      overactivity of NMDA receptor function due to facilitating NR2B tyrosine
      phosphorylation dependent on Fyn kinase by regulating interactions of Fyn with
      NR2B under the pathological conditions of LID.

PMID- 25565774
TI  - Clinicopathological significance and potential drug target of T-cadherin in
      NSCLC.
AB  - BACKGROUND: Previous studies demonstrate that T-cadherin is a candidate tumor
      suppressor in several types of human tumors, including non-small cell lung cancer
      (NSCLC). Lack of protein expression of T-cadherin by hypermethylation has been
      found to play an important role in lung alveolar differentiation regulation and
      epithelial tumorigenesis. However, the correlation between T-cadherin
      hypermethylation and clinicopathological characteristics of NSCLC remains
      unclear. Here we conducted a systematic review and meta-analysis to
      quantitatively evaluate the effects of T-cadherin hypermethylation on the
      incidence of NSCLC and clinicopathological characteristics. METHODS: A detailed
      literature search was carried out for related research publications. Analyses of
      pooled data were performed. Odds ratio (OR) and hazard ratio (HR) were calculated
      and summarized, respectively. RESULTS: Final analysis of 1,172 NSCLC patients
      from 15 eligible studies was performed. T-cadherin hypermethylation was observed
      to be significantly higher in NSCLC than in normal lung tissue, based on the
      pooled OR from nine studies including 532 NSCLC and 372 normal lung tissue
      samples (OR=8.19, 95% confidence interval [CI]=5.41-12.39, P<0.00001). T-cadherin
      hypermethylation may also be associated with pathological types. The pooled OR
      was obtained from four studies including 111patients with squamous cell carcinoma
      and 106 with adenocarcinoma (OR=0.35, 95% CI=0.19-0.66, P=0.001), which indicated
      that T-cadherin hypermethylation plays a more important role in the pathogenesis
      of adenocarcinoma. We did not find that T-cadherin hypermethylation was
      correlated with the sex or smoking status, clinical stages, or epidermal growth
      factor receptor (EGFR) mutation status. However, T-cadherin hypermethylation was
      found to be significantly higher in poorly differentiated NSCLC than in
      moderately and highly differentiated NSCLC, and NSCLC patients with T-cadherin
      hypermethylation had a lower survival rate than those without T-cadherin
      hypermethylation. CONCLUSION: The results of this meta-analysis suggest that T
      cadherin hypermethylation is associated with an increased risk and worse survival
      in NSCLC. T-cadherin hypermethylation, which induces the inactivation of T
      cadherin gene, plays an important role in the carcinogenesis, cancer progression,
      as well as clinical outcome.

PMID- 25565775
TI  - Synthesis and characterization of a novel chemically designed (Globo)3-DTPA-KLH
      antigen.
AB  - In recent years, many experiments have been conducted for the production and
      evaluation of anticancer glycoconjugated vaccines in developed countries and many
      achievements have been accomplished with Globo H derivatives. In the current
      experiment, a new chemically designed triplicate version of (Globo H)3
      diethylenetriamine pentaacetic acid (DTPA)-KLH antigen was synthesized and
      characterized. Immunization with (Globo H)3-DTPA-KLH, a hexasaccharide that is a
      member of a family of antigenic carbohydrates that are highly expressed in
      various types of cancers conjugated with DTPA and KLH protein, induced a high
      level of antibody titer along with an elevated level of IL-4 in mice. Treatment
      of tumors with the collected sera from immunized mice decreased the tumor size in
      nude mice as well. None of the immunized mice illustrated any sign of tumor
      growth after injection of MCF-7 cells compared to the control animals. These
      findings, based on the newly presented structure of the Globo H antigen, lend
      exciting and promising evidence for clinical advancement in the development of a
      therapeutic vaccine in the future. 

PMID- 25565777
TI  - Comparison of peginterferon alfa-2a and alfa-2b for treatment of patients with
      chronic hepatitis C: a retrospective study using the Japanese Interferon
      Database.
AB  - PURPOSE: We aimed to compare the rates of sustained virologic response (SVR)
      achieved with peginterferon (PEG-IFN) alfa-2a and alfa-2b in combination with
      ribavinin (RBV) for chronic hepatitis C, using a large database of hepatitis
      cases to improve the generalizability of these results. METHODS: We identified
      patients with chronic hepatitis C who were treated with PEG-IFN alfa-2a or alfa
      2b and RBV, from the Japanese Interferon Database, between December 2009 and
      April 2013. This database contains the medical records of IFN treatment collected
      from 36 prefectures in Japan. Multivariable logistic regression analysis was used
      to compare SVR rates obtained with PEG-IFN alfa-2a and alfa-2b, in combination
      with RBV. RESULTS: A total of 16,349 patients were recorded in the Japanese
      Interferon Database. After application of the exclusion criteria, 12,706 patients
      (3,578 [1,710 males, 1,868 females] on PEG-IFN alfa-2a; and 9,128 [4,652 males,
      4,476 females] on PEG-IFN alfa-2b) were included in this analysis. The SVR rate
      in the PEG-IFN alfa-2b group was 62.0%, as compared with a rate of 55.1% in the
      PEG-IFN alfa-2a group (crude odds ratio =1.31; 95% confidence interval [CI]: 1.23
      to 1.44). There was no significant difference in the adjusted SVR rates between
      the two groups (adjusted odds ratio =0.96; 95% CI: 0.88 to 1.05). Similar
      proportions of adverse events were observed in the two groups, with the exception
      of thrombocytopenia, retinopathy, and anemia. CONCLUSION: There was no
      significant difference in the SVR rates and safety profile between chronic
      hepatitis C patients treated with the PEG-IFN alfa-2a and alfa-2b.

PMID- 25565778
TI  - Prevalence and individual risk factors associated with clinical lumbar
      instability in rice farmers with low back pain.
AB  - INTRODUCTION: Clinical lumbar instability (CLI) is one of the subgroups of
      chronic non-specific low back pain. Thai rice farmers often have poor sustained
      postures during a rice planting process and start their farming at an early age.
      However, individual associated factors of CLI are not known and have rarely been
      diagnosed in low back pain. This study aimed to determine the prevalence and
      individual associated factors of CLI in Thai rice farmers. METHODS: A cross
      sectional survey was conducted among 323 Thai rice farmers in a rural area of
      Khon Kaen province, Thailand. Face-to-face interviews were conducted using the 13
      item Delphi criteria questionnaire, after which an objective examination was
      performed using aberrant movement sign, painful catch sign, and prone instability
      test to obtain information. Individual factors such as sex, body mass index,
      waist-hip ratio, smoking, and number of years of farming experience, were
      recorded during the face-to-face interview. RESULTS: The prevalence of CLI in
      Thai rice farmers calculated by the method described in this study was 13% (age
      44+/-10 years). Number of years of farming experience was found to be
      significantly correlated with the prevalence of CLI (adjusted odds ratio =2.02,
      95% confidence interval =1.03-3.98, P<0.05). CONCLUSION: This study provides
      prevalence of CLI in Thai rice farmers. Those with long-term farming experience
      of at least 30 years have a greater risk of CLI.

PMID- 25565776
TI  - Coffee and caffeine potentiate the antiamyloidogenic activity of melatonin via
      inhibition of Abeta oligomerization and modulation of the Tau-mediated pathway in
      N2a/APP cells.
AB  - There is an increasing prevalence of Alzheimer's disease (AD), which has become a
      public health issue. However, the underlying mechanisms for the pathogenesis of
      AD are not fully understood, and the current therapeutic drugs cannot produce
      acceptable efficacy in AD patients. Previous animal studies have shown that
      coffee (Coff), caffeine (Caff), and melatonin (Mel) have beneficial effects on
      AD. Disturbed circadian rhythms are observed in AD, and chronotherapy has shown
      promising effects on AD. In this study, we examined whether a combination of Coff
      or Caff plus Mel produced a synergistic/additive effect on amyloid-beta (Abeta)
      generation in Neuro-2a (N2a)/amyloid precursor protein (APP) cells and the
      possible mechanisms involved. Cells were treated with Coff or Caff, with or
      without combined Mel, with three different chronological regimens. In regimen 1,
      cells were treated with Coff or Caff for 12 hours in the day, followed by Mel for
      12 hours in the night. For regimen 2, cells were treated with Coff or Caff plus
      Mel for 24 hours, from 7 am to 7 am the next day. In regimen 3, cells were
      treated with Coff or Caff plus Mel with regimen 1 or 2 for 5 consecutive days.
      The extracellular Abeta40/42 and Abeta oligomer levels were determined using
      enzyme-linked immunosorbent assay (ELISA) kits. The expression and/or
      phosphorylation levels of glycogen synthase kinase 3beta (GSK3beta), Erk1/2,
      PI3K, Akt, Tau, Wnt3alpha, beta-catenin, and Nrf2 were detected by Western blot
      assay. The results showed that regimen 1 produced an additive antiamyloidogenic
      effect with significantly reduced extracellular levels of Abeta40/42 and Abeta42
      oligomers. Regimen 2 did not result in remarkable effects, and regimen 3 showed a
      less antiamyloidogenic effect compared to regimen 1. Coff or Caff, plus Mel
      reduced oxidative stress in N2a/APP cells via the Nrf2 pathway. Coff or Caff,
      plus Mel inhibited GSK3beta, Akt, PI3K p55, and Tau phosphorylation but enhanced
      PI3K p85 and Erk1/2 phosphorylation in N2a/APP cells. Coff or Caff, plus Mel
      downregulated Wnt3alpha expression but upregulated beta-catenin. However, Coff or
      Caff plus Mel did not significantly alter the production of T helper cell (Th)1
      related interleukin (IL)-12 and interferon (IFN)-gamma and Th2-related IL-4 and
      IL-10 in N2a/APP cells. The autophagy of cells was not affected by the
      combinations. Taken together, combination of Caff or Coff, before treatment with
      Mel elicits an additive antiamyloidogenic effects in N2a/APP cells, probably
      through inhibition of Abeta oligomerization and modulation of the
      Akt/GSK3beta/Tau signaling pathway. 

PMID- 25565779
TI  - Cancer survivors' perspectives and experience on western medicine and traditional
      Chinese medicine treatment and rehabilitation: a qualitative study.
AB  - BACKGROUND: In the People's Republic of China, both western medicine (WM) and
      traditional Chinese medicine (TCM) are the main treatment and rehabilitation
      options for cancer patients. This study aimed to explore cancer survivors'
      perspectives and experience of treatment and rehabilitation, in order to promote
      patient-centered activities of treatment and rehabilitation. METHODS: Using a
      qualitative research approach, 68 cancer survivors were recruited from eight
      community cancer rehabilitation organizations in Shanghai, People's Republic of
      China. Eight focus group interviews were conducted. All these interviews were
      transcribed verbatim, and the data were analyzed by theme analysis. RESULTS: WM
      was the main choice in treatment phase though study participants noted more side
      effects. TCM was primarily used in the recovery phase. The lack of communication
      between doctors and cancer patients appears to affect treatment adherence and
      impair the doctor-patient relationship. WM was expensive for diagnostic
      procedures and treatment, while the cumulative costs of frequent use of TCM in
      the long rehabilitation period were also high. Both treatment options created
      significant perceived economic burden on patients. Conflicting information about
      dietary supplements tended to make cancer survivors confused. CONCLUSION:
      Improving the communication between doctors and cancer patients helps to
      ameliorate cancer patient adherence and the effect of treatments. It is essential
      to educate cancer patients about the effect and cost of both WM and traditional
      TCM. Meanwhile, marketing management and guidance to consumers regarding use of
      dietary supplements in the cancer rehabilitation field are also necessary.

PMID- 25565780
TI  - Assessing the adherence behavior of glaucoma patients to topical eye drops.
AB  - PURPOSE: The goal of this study was to determine the adherence of glaucoma
      patients to their topical glaucoma medication. Furthermore, the relationships
      between the adherence behavior and the patients' demographic data, clinical
      characteristics, and their knowledge about glaucoma were evaluated. METHODS: This
      was a prospective study of 123 patients with primary open-angle glaucoma who were
      given two standardized questionnaires. The first questionnaire at time point T1
      comprised a knowledge assessment and the self-reported adherence measures
      Adherence to Refills and Medication Scale 2 (ARMS2), visual analogue scale for
      adherence (VAS-AD), and missed doses in the past 14 days. Two months later at
      time point T2, a second questionnaire reevaluated the adherence measures ARMS2,
      VAS-AD, and missed doses in the past 14 days. RESULTS: There was a good
      correlation among all the three adherence measures at T1 and T2. The mean values
      of ARMS2 were in the lower range, with 3.38 at T1 and 2.8 at T2. The VAS-AD
      detected that 18.5% of patients always took their eye drops correctly, and 77.9%
      of patients reported not to have missed a single dose in the past 14 days. There
      was no significant correlation between the patients' demographic data or
      knowledge about glaucoma and the adherence measures ARMS2 or VAS-AD. Among the
      clinical characteristics, only single-eye blindness showed a significant
      correlation with VAS-AD. CONCLUSION: In this study, no general relationships were
      found between medication adherence and the patients' demographic data, clinical
      characteristics, or knowledge about glaucoma. It may be assumed that more
      individualized strategies are required to optimize adherence behavior.

PMID- 25565781
TI  - Patient perspectives of telemedicine quality.
AB  - BACKGROUND: The purpose of this study was to explore the quality attributes
      required for effective telemedicine encounters from the perspective of the
      patient. METHODS: We used a multi-method (direct observation, focus groups,
      survey) field study to collect data from patients who had experienced
      telemedicine encounters. Multi-perspectives (researcher and provider) were used
      to interpret a rich set of data from both a research and practice perspective.
      RESULTS: The result of this field study is a taxonomy of quality attributes for
      telemedicine service encounters that prioritizes the attributes from the patient
      perspective. We identify opportunities to control the level of quality for each
      attribute (ie, who is responsible for control of each attribute and when control
      can be exerted in relation to the encounter process). This analysis reveals that
      many quality attributes are in the hands of various stakeholders, and all
      attributes can be addressed proactively to some degree before the encounter
      begins. CONCLUSION: Identification of the quality attributes important to a
      telemedicine encounter from a patient perspective enables one to better design
      telemedicine encounters. This preliminary work not only identifies such
      attributes, but also ascertains who is best able to address quality issues prior
      to an encounter. For practitioners, explicit representation of the quality
      attributes of technology-based systems and processes and insight on controlling
      key attributes are essential to implementation, utilization, management, and
      common understanding.

PMID- 25565782
TI  - Efficacy and tolerability of low-dose oral prolonged-release oxycodone/naloxone
      for chronic nononcological pain in older patients.
AB  - PURPOSE: Chronic pain is highly prevalent in older adults. Increasing evidence
      indicates strong opioids as a valid option for chronic pain management in
      geriatrics. The aim of this study was to evaluate efficacy and safety of low-dose
      oral prolonged-release oxycodone-naloxone (OXN-PR) in patients aged >=70 years.
      METHODS: This open-label prospective study assessed older patients naive to
      strong opioids presenting with moderate-to-severe chronic pain. Patients were
      prescribed OXN-PR at an initial dose of 10/5 mg/day for 28 days. In case of
      insufficient analgesia, the initial daily dose could be increased gradually. The
      primary efficacy measure was change in pain intensity from baseline, assessed by
      a ten-point Numeric Rating Scale (NRS) at day 28 (T28). Changes in cognitive
      state, daily functioning, quality of life, constipation, and other adverse events
      were assessed. RESULTS: Of 53 patients enrolled (mean 81.7+/-6.2 years [range 70
      92 years]), 52 (98.1%) completed the 28-day observation. At T28, the primary end
      point (>=30% reduction in mean pain from baseline in the absence of bowel
      function deterioration) was achieved in 38 patients (71.7%). OXN-PR significantly
      relieved pain (NRS score -3.26; P<0.0001), as well as daily need for rescue
      paracetamol (from 86.8% at baseline to 40.4% at T28; P<0.001), and reduced impact
      of pain on daily activities (Brief Pain Inventory Short Form from 6.2+/-1.5 to
      3.4+/-2.1; P<0.0001). OXN-PR was also associated with significant improvement in
      daily functioning (Barthel Index from 53.3+/-14.1 to 61.3+/-14.3; P<0.01). No
      changes were observed in cognitive status and bowel function. OXN-PR was well
      tolerated; only one patient (1.9%) prematurely withdrew from treatment, due to
      drowsiness. CONCLUSION: Findings from this open-label prospective study suggest
      that low-dose OXN-PR may be effective and well tolerated for treatment of
      moderate-to-severe chronic pain in older patients. Besides its effectiveness,
      these data indicate that low-dose OXN-PR may be considered a safe analgesic
      option in this fragile population and warrants further investigation in
      randomized controlled studies.

PMID- 25565784
TI  - Influence of oral health condition on swallowing and oral intake level for
      patients affected by chronic stroke.
AB  - BACKGROUND: According to the literature, the occurrence of dysphagia is high in
      cases of stroke, and its severity can be enhanced by loss of teeth and the use of
      poorly fitting prostheses. OBJECTIVE: To verify that the status of oral health
      influences the level of oral intake and the degree of swallowing dysfunction in
      elderly patients with stroke in chronic phase. METHODS: Thirty elderly
      individuals affected by stroke in chronic phase participated. All subjects
      underwent assessment of their oral condition, with classification from the
      Functional Oral Intake Scale (FOIS) and nasoendoscopic swallowing assessment to
      classify the degree of dysphagia. The statistical analysis examined a
      heterogeneous group (HG, n=30) and two groups designated by the affected body
      part, right (RHG, n=8) and left (LHG, n=11), excluding totally dentate or
      edentulous individuals without rehabilitation with more than one episode of
      stroke. RESULTS: There was a negative correlation between the need for
      replacement prostheses and the FOIS scale for the HG (P=0.02) and RHG (P=0.01).
      Differences in FOIS between types of prostheses of the upper dental arch in the
      LHG (P=0.01) and lower dental arch in the RHG (P=0.04). A negative correlation
      was found between the number of teeth present and the degree of dysfunction in
      swallowing liquid in the LHG (P=0.05). There were differences in the performance
      in swallowing solids between individuals without prosthesis and those with
      partial prosthesis in the inferior dental arch (P=0.04) for the HG. CONCLUSION:
      The need for replacement prostheses, type of prostheses, and the number of teeth
      of elderly patients poststroke in chronic phase showed an association with the
      level of oral intake and the degree of oropharyngeal dysphagia.

PMID- 25565783
TI  - Preoperative assessment of the older surgical patient: honing in on geriatric
      syndromes.
AB  - Nearly 50% of Americans will have an operation after the age of 65 years.
      Traditional preoperative anesthesia consultations capture only some of the
      information needed to identify older patients (defined as >=65 years of age)
      undergoing elective surgery who are at increased risk for postoperative
      complications, prolonged hospital stays, and delayed or hampered functional
      recovery. As a catalyst to this review, we compared traditional risk scores (eg,
      cardiac-focused) to geriatric-specific risk measures from two older female
      patients seen in our preoperative clinic who were scheduled for elective, robotic
      assisted hysterectomies. Despite having a lower cardiac risk index and Charlson
      comorbidity score, the younger of the two patients presented with more subtle
      negative geriatric-specific risk predictors - including intermediate or pre-frail
      status, borderline malnutrition, and reduced functional/mobility - which may have
      contributed to her 1-day-longer length of stay and need for readmission. Adequate
      screening of physiologic and cognitive reserves in older patients scheduled for
      surgery could identify at-risk, vulnerable elders and enable proactive
      perioperative management strategies (eg, strength, balance, and mobility
      prehabilitation) to reduce adverse postoperative outcomes and readmissions. Here,
      we describe our initial two cases and review the stress response to surgery and
      the impact of advanced age on this response as well as preoperative geriatric
      assessments, including frailty, nutrition, physical function, cognition, and mood
      state tests that may better predict postoperative outcomes in older adults. A
      brief overview of the literature on anesthetic techniques that may influence
      geriatric-related syndromes is also presented. 

PMID- 25565787
TI  - Association between resting heart rate and N-terminal pro-brain natriuretic
      peptide in a community-based population study in Beijing.
AB  - BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) is associated
      with an increased risk of cardiac insufficiency, which possibly leads to heart
      failure. However, the relationship between resting heart rate and NT-proBNP is
      unclear. OBJECTIVE: This study focuses on this relativity between resting heart
      rate and plasma NT-proBNP levels in a surveyed community-based population.
      METHODS: We evaluated the relativity between resting heart rate and plasma levels
      of NT-proBNP in 1,567 participants (mean age 61.0 years, range 21-96 years) from
      a community-based population in Beijing, People's Republic of China. RESULTS: In
      patients with high resting heart rate (>=75 beats/min), NT-proBNP was higher than
      in those having low resting heart rate (<75 beats/min). In multiple linear
      stepwise regression analysis, plasma NT-proBNP was associated with resting heart
      rate (partial correlation coefficient, 0.82; 95% confidence interval, 0.18-1.51;
      P=0.011). A subsequent subgroup analysis revealed that the association between
      resting heart rate and plasma NT-proBNP was strengthened in subjects over 60
      years old (partial correlation coefficient 1.28; 95% confidence interval, 0.49
      2.36; P=0.031); while the relativity between resting heart rate and plasma NT
      proBNP was not emerged in the younger subgroup (<60 years old). CONCLUSIONS:
      Resting heart rate was associated with plasma NT-proBNP in the elderly, which
      indicated a relationship between resting heart rate and cardiac function damage.

PMID- 25565788
TI  - Functional assessment of geriatric patients in regard to health-related quality
      of life (HRQoL).
AB  - PURPOSE: The main aim of our research was to evaluate general health,
      functioning, and performance parameters, as well as care problems of Geriatric
      Clinic inpatients in relation to deficits in fulfilling needs. The assessment of
      health-related quality of life was also performed. PATIENTS AND METHODS: The
      research subjects were patients attending the Clinic of Geriatrics: 149 women and
      78 men; 227 persons in total. The research was carried out using a diagnostic
      poll method, with the application of the Activities of Daily Living questionnaire
      of assessment of daily efficiency on the basis of the Katz index, the
      Instrumental Activities of Daily Living questionnaire, the Care Dependency Scale
      used to measure the level of care dependency and human needs, and the Nottingham
      Health Profile scale. RESULTS: The results showed that the majority of
      respondents achieved high and medium levels of functional capability. The main
      problems associated with the fulfillment of needs were difficulties with the
      adoption of appropriate body posture, movement restrictions, and problems related
      to participating in unassisted leisure activities outside the home. The general
      deficit in fulfilling the needs of the patients was low. The most significant
      problems were related to sleep disorders, restrictions in freedom of movement,
      loss of vital energy, and ailments resulting in the observable presence of pain.
      CONCLUSION: Good daily functioning of elderly patients significantly depended on
      their intellectual and mental efficiency. Elderly patients require a
      comprehensive, holistic approach to a variety of problems that occur with aging.

PMID- 25565786
TI  - Does food insufficiency in childhood contribute to dementia in later life?
AB  - BACKGROUND: Despite several studies attempting to identify the risk factors for
      dementia, little is known about the impact of childhood living conditions on
      cognitive function in later life. The present study aims to examine the unique
      contribution of food insufficiency in childhood to dementia in old age. METHODS:
      Data for this study of 2,745 older Malaysians aged 60 years and older was
      obtained from a national survey entitled "Mental Health and Quality of Life of
      Older Malaysians" conducted from 2003 through 2005 using a cross-sectional
      design. The Geriatric Mental State-Automated Geriatric Examination for Computer
      Assisted Taxonomy was used to measure dementia. A multiple binary logistic
      regression using Statistical Package for Social Sciences version 21 was conducted
      to assess the unique effect of food insufficiency in childhood on developing
      dementia in old age. RESULTS: A notably higher prevalence of dementia was found
      in respondents who indicated they had experienced food insufficiency in childhood
      than in their food-sufficient counterparts (23.5% versus 14.3%). The findings
      from multiple logistic regression analysis revealed that food insufficiency in
      childhood would independently increase the risk of developing dementia in old age
      by 81%, after adjusting for sociodemographic factors (odds ratio =1.81, 95%
      confidence interval 1.13-2.92, P<0.01). CONCLUSION: Findings from the present
      study showing that food insufficiency in early life significantly contributes to
      dementia in later life highlight the importance of childhood living conditions in
      maintaining cognitive function in old age. It is, therefore, suggested that older
      adults with childhood food insufficiency might be targeted for programs designed
      to prevent dementia.

PMID- 25565785
TI  - CANTAB object recognition and language tests to detect aging cognitive decline:
      an exploratory comparative study.
AB  - OBJECTIVE: The recognition of the limits between normal and pathological aging is
      essential to start preventive actions. The aim of this paper is to compare the
      Cambridge Neuropsychological Test Automated Battery (CANTAB) and language tests
      to distinguish subtle differences in cognitive performances in two different age
      groups, namely young adults and elderly cognitively normal subjects. METHOD: We
      selected 29 young adults (29.9+/-1.06 years) and 31 older adults (74.1+/-1.15
      years) matched by educational level (years of schooling). All subjects underwent
      a general assessment and a battery of neuropsychological tests, including the
      Mini Mental State Examination, visuospatial learning, and memory tasks from
      CANTAB and language tests. Cluster and discriminant analysis were applied to all
      neuropsychological test results to distinguish possible subgroups inside each age
      group. RESULTS: Significant differences in the performance of aged and young
      adults were detected in both language and visuospatial memory tests. Intragroup
      cluster and discriminant analysis revealed that CANTAB, as compared to language
      tests, was able to detect subtle but significant differences between the
      subjects. CONCLUSION: Based on these findings, we concluded that, as compared to
      language tests, large-scale application of automated visuospatial tests to assess
      learning and memory might increase our ability to discern the limits between
      normal and pathological aging.

PMID- 25565789
TI  - Fibromyalgia with severe forms of progression in a multidisciplinary therapy
      setting with emphasis on hyperthermia therapy--a prospective controlled study.
AB  - INTRODUCTION: Fibromyalgia syndrome (FMS) is a multi-factorial disease involving
      physiological as well as psychological factors. The aim of the study was to
      investigate a multidisciplinary inpatient treatment with emphasis on hyperthermia
      therapy by patients with widespread pain. MATERIALS AND METHODS: The study
      involved 104 patients suffering from severely progressive FMS. A convenience
      sample and a prospective cohort design were used. The patients were treated in an
      acute hospital focusing on rheumatologic pain therapy and multidisciplinary
      complementary medicine. One patient group was treated with inclusion of
      hyperthermia therapy and the other group without. The therapy density (number of
      performed therapies per patient) was determined for every patient. Functional
      capacity measured by the Hannover functional status questionnaire
      (Funktionsfragebogen Hannover) and symptoms (von Zerssen complaint list) were
      analyzed for both groups on admission and on discharge. RESULTS: On admission, no
      significant difference could be established between control group (CG; multimodal
      without hyperthermia) and hyperthermia group (HG; multimodal with hyperthermia)
      (functional capacity, P=0.936). Functional capacity improved for the CG and the
      HG. On discharge, there was a significant difference between the two groups
      (functional capacity, P=0.039). There were no significant differences in
      fibromyalgia symptoms between CG (mean 41.8) and HG (mean 41.8) on their
      admission to hospital (P=0.988). On discharge, there was a significant difference
      (P=0.024) between the two groups (HG, mean 30.6; CG, mean 36.6). The inpatient
      therapy of patients with severely progressive fibromyalgia is characterized by a
      high frequency of therapy input. CONCLUSION: FMS, especially with severe
      progression and a high degree of chronification, demands a multidisciplinary
      approach. In addition to the use of complementary medical procedures, integration
      of hyperthermia in the treatment process is a useful option.

PMID- 25565790
TI  - Impact of chronic obstructive pulmonary diseases on left ventricular diastolic
      function in hospitalized elderly patients.
AB  - OBJECTIVE: To evaluate the impact of chronic obstructive pulmonary disease (COPD)
      on left ventricular (LV) diastolic function in hospitalized elderly patients.
      METHODS: This was a case-control observational study of 148 consecutive
      hospitalized elderly patients (>=65 years old): 73 subjects without COPD as
      controls and 75 patients with COPD. Mild-to-moderate COPD was defined as stages 1
      and 2, while severe and very severe COPD was defined as stages 3 and 4, according
      to the Global Initiative for Chronic Obstructive Lung Disease guidelines.
      Clinical characteristics and echocardiographic parameters were analyzed and
      compared. RESULTS: Compared with the control group, patients with COPD had a
      higher frequency of LV diastolic dysfunction and heart failure with preserved
      ejection fraction. Smoking frequency, frequency of cerebrovascular diseases and
      diabetes, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels
      were higher in the COPD group (all P<0.05). COPD patients showed more
      abnormalities in diastolic function (E/e': 11.51+/-2.50 vs 10.42+/-3.25,
      P=0.047), but no differences in systolic function and right ventricular function
      (all P>0.05). Patients with severe/very severe COPD showed no differences in LV
      diastolic function compared to patients with mild/moderate COPD (P>0.05), but
      serum NT-proBNP levels were higher in severe/very severe COPD (P<0.05).
      CONCLUSION: Results suggest that early-stage COPD may have an impact on the LV
      diastolic function. Severe COPD mainly affected right ventricular function. In
      hospitalized elderly patients with COPD, LV diastolic dysfunction should be taken
      into account together with right ventricular function.

PMID- 25565791
TI  - Serum total prostate-specific antigen values in men with symptomatic prostate
      enlargement in Nigeria: role in clinical decision-making.
AB  - BACKGROUND: Prostatic enlargement is a common cause of bladder outlet obstruction
      in men in Nigeria. Malignant enlargements must be differentiated from benign
      enlargements for adequate treatment of each patient. High serum total prostate
      specific antigen (tPSA) levels suggest malignancy, but some of the biopsies done
      due to a serum tPSA value >4 ng/mL would be negative for malignancy because of
      the low specificity of tPSA for prostate cancer. This study aims to compare the
      histologic findings of all prostate specimens obtained from core needle biopsy,
      open simple prostatectomy, and transurethral resection of the prostate with the
      respective serum tPSA values in an attempt to decipher the role of serum tPSA in
      the management of these patients. METHODS: The case notes of patients attended to
      from April 2009 to March 2012 were analyzed. Essentially, the age of the patient,
      findings on digital rectal examination, abdominopelvic ultrasonography report on
      the prostate, serum tPSA, and histology reports from biopsy or prostatectomy
      specimens as indicated were extracted for analysis. RESULTS: The relationship
      between age, findings on digital rectal examination, serum tPSA, abdominopelvic
      ultrasonography report, and histology are compared. A statistically significant
      relationship existed between a malignant histology and age 65 years and older,
      suspicious findings on digital rectal examination, suspicious ultrasonography
      findings, and serum tPSA >10 ng/mL, but not tPSA >4 ng/mL. CONCLUSION: In
      Nigerian patients with symptomatic prostate enlargement, serum tPSA should be
      seen as a continuum with increasing risk of prostate malignancy.

PMID- 25565792
TI  - The development of individual cognitive stimulation therapy (iCST) for dementia.
AB  - BACKGROUND: Adopting a systematic approach to the development of an intervention,
      supported by robust theoretical, empirical, and clinical rationales represents
      best practice. The Medical Research Council (MRC) provides a framework for a
      systematic step-wise approach to the evaluation of complex interventions. This
      study describes the development phase of the individual cognitive stimulation
      therapy (iCST) for dementia trial, within this framework. METHODS: In the
      preclinical phase, a recent Cochrane Review of cognitive stimulation for dementia
      and the current literature on individual cognitive stimulation interventions were
      examined to establish an evidence base. In addition, people with dementia,
      carers, and care staff were consulted regarding the acceptability of iCST, and a
      panel was put together to advise the team on the adaptation of group cognitive
      stimulation therapy (CST). Phase I (modeling) involved consultations with service
      users and experts in a series of focus groups, interviews, an online survey, and
      a consensus conference. Finally, Phase II field testing of the intervention was
      carried out. RESULTS: Two drafts of the materials were produced before a final
      version ready for use in the main randomized controlled trial (RCT). Key changes
      between the drafts included: editorial amendments to improve the clarity of
      instructions, emphasize the person centeredness of the approach, and reduce the
      overall length of the introduction section; the simplification of academic
      terminology and activities deemed "too difficult"; adjustments made to the
      monitoring-progress forms and session rating scale to enhance user-friendliness;
      the addition of a "Getting started" section; amendments made to the content of
      the toolkit; and clearer distinction made between the level of difficulty of
      activities. CONCLUSION: The rigorous development of the intervention was
      beneficial as the feasibility of the intervention was explored both in theory and
      practice, and consulting with service users ensured that materials were
      appropriately tailored to their needs. A Phase III RCT is currently being
      conducted to determine the effectiveness of iCST.

PMID- 25565793
TI  - Treatment of primary osteoporosis in men.
AB  - With the aging of the population worldwide, osteoporosis and osteoporotic
      fractures are becoming a serious health care issue in the Western world. Although
      less frequent than in women, osteoporosis in men is a relatively common problem.
      Hip and vertebral fractures are particularly relevant, being associated with
      significant mortality and disability. Since bone loss and fragility fractures in
      men have been recognized as serious medical conditions, several randomized
      controlled trials (RCTs) have been undertaken in males with osteoporosis to
      investigate the anti-fracture efficacy of the pharmacological agents commonly
      used to treat postmenopausal osteoporosis. Overall, treatments for osteoporosis
      in men are less defined than in women, mainly due to the fact that there are
      fewer RCTs performed in male populations, to the relatively smaller sample sizes,
      and to the lack of long-term extension studies. However, the key question is
      whether men are expected to respond differently to osteoporosis therapies than
      women. The pharmacological properties of bisphosphonates, teriparatide,
      denosumab, and strontium ranelate make such differentiation unlikely, and
      available clinical data support their efficacy in men with primary osteoporosis
      as well as in women. In a series of well-designed RCTs, alendronate, risedronate,
      zoledronic acid, and teriparatide were demonstrated to reduce the risk of new
      vertebral fractures in men presenting with primary osteoporosis (including
      osteoporosis associated with low testosterone levels) and to improve the bone
      mineral density (BMD). In preliminary studies, ibandronate, denosumab, and
      strontium ranelate also showed their beneficial effects on surrogate outcomes
      (BMD and markers of bone turnover) in men with osteoporosis. Although direct
      evidence about their non-vertebral anti-fracture efficacy are lacking, the
      effects of bisphosphonates, denosumab, teriparatide, and strontium ranelate on
      surrogate outcomes (BMD and markers of bone turnover) were similar to those
      reported in pivotal RCTs undertaken in postmenopausal women, in which vertebral
      and non-vertebral anti-fracture efficacy have been clearly demonstrated. In
      conclusion, sufficient data exist to support the use of these pharmacological
      agents in men with primary osteoporosis. Further RCTs are warranted to establish
      their long-term efficacy and safety. 

PMID- 25565794
TI  - Knowledge about COPD among users of primary health care services.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often underdiagnosed,
      which might be attributable to a lack of knowledge about the disease among the
      general population. The objective of this study was to evaluate COPD-related
      knowledge among primary care users in an urban area in Brazil. METHODS: This
      study was carried out at primary care clinics (PCCs), including 12 general PCCs
      and 26 family health PCCs, in the city of Goiania, Brazil. Between May 2013 and
      February 2014, we interviewed 674 PCC users, applying a questionnaire designed to
      assess COPD-related knowledge. Satisfactory knowledge of COPD was defined as
      knowing at least two of its symptoms and that smoking is a risk factor for the
      disease. RESULTS: Of the 674 users interviewed, only 9.2% recognized the term
      "COPD", 75.1% recognized the term "emphysema", and 15.7% did not recognize either
      term. We found that recognizing either term was associated with a higher level of
      education (P<0.001). The prevalence of satisfactory knowledge of COPD was 16.2%,
      and having such knowledge was associated with being over 60 years of age. The
      COPD symptom known by the greatest proportion of users (70.6%) was dyspnea, and
      most (87.5%) knew that smoking is a risk factor, whereas only a few (4.9%) knew
      that exposure to wood smoke is also a risk factor. The most frequently cited
      sources of knowledge were the media (43.1%) and a relative with COPD (36.4%).
      CONCLUSION: Most of the PCC users evaluated did not know the term "COPD" but were
      familiar with the term "emphysema". The level of basic knowledge about the
      disease was low in this population. These results should alert health care
      administrators to the need for interventions aimed at increasing the diagnosis
      rate and thus promoting the early treatment of COPD.

PMID- 25565795
TI  - Association of genetic polymorphisms with chronic obstructive pulmonary disease
      in the Hainan population: a case-control study.
AB  - PURPOSE: Chronic obstructive pulmonary disease (COPD) is predicted to become the
      third most common cause of death and the fifth most common cause of disability in
      the world by 2020. Recently, variants in the hypoxia-inducible factor 1alpha
      (HIF1A), cholinergic receptor, neuronal nicotinic, alpha polypeptide-5, and iron
      responsive element-binding protein 2 gene (IREB2) genes were found to be
      associated with COPD. This study aims to identify whether the variations in these
      genes are related to COPD in the Hainan population of the People's Republic of
      China. PATIENTS AND METHODS: We genotyped 12 single nucleotide polymorphisms in a
      case-control study with 200 COPD cases and 401 controls from Hainan, People's
      Republic of China. Odds ratios and 95% confidence intervals were estimated using
      the chi-squared (chi(2)) test, genetic model analysis, haplotype analysis, and
      stratification analysis. RESULTS: In the genetic model analysis, we found that
      the genotype T/T of rs13180 of IREB2 decreased the COPD risk by 0.52-fold
      (P=0.025). But in the further stratification analysis, we failed to find the
      association between the selected single nucleotide polymorphisms with COPD risk
      in Han population. In addition, the haplotype analysis of HIF1A gene also was not
      found to be the possible haplotype associated with COPD risk. CONCLUSION: Our
      results support that IREB2 rs13180 is associated with COPD in Hainan population.
      And this is the first time the HIF1A polymorphisms in COPD in a Chinese
      population has been reported, although we failed to find any significant result.

PMID- 25565796
TI  - Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol
      pharmacokinetics and safety: a single-blind, nonrandomized study.
AB  - BACKGROUND: Umeclidinium and vilanterol, long-acting bronchodilators for the
      treatment of chronic obstructive pulmonary disease, are primarily eliminated via
      the hepatic route; however, severe renal impairment may adversely affect some
      elimination pathways other than the kidney. OBJECTIVES: To evaluate the effect of
      severe renal impairment on the pharmacokinetics of umeclidinium and
      umeclidinium/vilanterol. METHODS: Nine patients with severe renal impairment
      (creatinine clearance <30 mL/min) and nine matched healthy volunteers received a
      single dose of umeclidinium 125 MUg; and after a 7- to 14-day washout, a single
      dose of umeclidinium/vilanterol 125/25 MUg. RESULTS: No clinically relevant
      increases in plasma umeclidinium or vilanterol systemic exposure (area under the
      curve or maximum observed plasma concentration) were observed following
      umeclidinium 125 MUg or umeclidinium/vilanterol 125/25 MUg administration. On
      average, the amount of umeclidinium excreted in 24 hours in urine (90% confidence
      interval) was 88% (81%-93%) and 89% (81%-93%) lower in patients with severe renal
      impairment compared with healthy volunteers following umeclidinium 125 MUg and
      umeclidinium/vilanterol 125/25 MUg administration, respectively. Treatments were
      well tolerated in both populations. CONCLUSION: Umeclidinium 125 MUg or
      umeclidinium/vilanterol 125/25 MUg administration to patients with severe renal
      impairment did not demonstrate clinically relevant increases in systemic exposure
      compared with healthy volunteers. No dose adjustment for umeclidinium and
      umeclidinium/vilanterol is warranted in patients with severe renal impairment.

PMID- 25565797
TI  - The added value of hybrid ventilation/perfusion SPECT/CT in patients with stable
      COPD or apparently healthy smokers. Cancer-suspected CT findings in the lungs are
      common when hybrid imaging is used.
AB  - Ventilation/perfusion (V/P) single-photon emission computed tomography (SPECT) is
      recognized as a diagnostic method with potential beyond the diagnosis of
      pulmonary embolism. V/P SPECT identifies functional impairment in diseases such
      as heart failure (HF), pneumonia, and chronic obstructive pulmonary disease
      (COPD). The development of hybrid SPECT/computed tomography (CT) systems,
      combining functional with morphological imaging through the addition of low-dose
      CT (LDCT), may be useful in COPD, as these patients are prone to lung cancer and
      other comorbidities. The aim of this study was to investigate the added value of
      LDCT among healthy smokers and patients with stable COPD, when examined with V/P
      SPECT/CT hybrid imaging. Sixty-nine subjects, 55 with COPD (GOLD I-IV) and 14
      apparently healthy smokers, were examined with V/P SPECT and LDCT hybrid imaging.
      Spirometry was used to verify COPD grade. Only one apparently healthy smoker and
      three COPD patients had a normal or nearly normal V/P SPECT. All other patients
      showed various degrees of airway obstruction, even when spirometry was normal.
      The same interpretation was reached on both modalities in 39% of the patients.
      LDCT made V/P SPECT interpretation more certain in 9% of the patients and, in
      52%, LDCT provided additional diagnoses. LDCT better characterized the type of
      emphysema in 12 patients. In 19 cases, tumor-suspected changes were reported.
      Three of these 19 patients (ie, 4.3% of all subjects) were in the end confirmed
      to have lung cancer. The majority of LDCT findings were not regarded as
      clinically significant. V/P SPECT identified perfusion patterns consistent with
      decompensated left ventricular HF in 14 COPD patients. In 16 patients (23%),
      perfusion defects were observed. HF and perfusion defects were not recognized
      with LDCT. In COPD patients and long-time smokers, hybrid imaging had added value
      compared to V/P SPECT alone, by identifying patients with lung malignancy and
      more clearly identifying emphysema. V/P SPECT visualizes comorbidities to COPD
      not seen with LDCT, such as pulmonary embolism and left ventricular HF. 

PMID- 25565798
TI  - Smoking-associated fibrosis and pulmonary asbestosis.
AB  - The diagnosis of pulmonary asbestosis is most often established based on clinical
      criteria and has both clinical and legal implications. Unfortunately, one of the
      confounding features in the diagnosis may be a history of cigarette abuse, which
      can produce interstitial opacities on chest imaging as well as diffusion defects
      on pulmonary function testing, criteria that are used in the diagnosis of
      pulmonary asbestosis. The objective of the present study was to evaluate the
      correlation of radiographically detected pulmonary fibrosis with fibrosis
      established histopathologically as attributable to asbestos, in a cohort referred
      for diagnosis of an asbestos-related malignancy in the context of litigation. We
      examined the slides of 186 cases with reported asbestos exposure, referred in
      consultation for asbestos-related malignancy and the presence of pulmonary
      fibrosis. Sixty-five cases had what was judged to be adequate tissue sampling for
      histopathologic evaluation of asbestosis as well as an existing radiologic
      assessment of pulmonary fibrosis by B-reader report. Of 24 cases judged to have
      asbestosis radiographically, which had sufficient tissue for pathologic
      examination, six showed asbestosis histopathologically. The remaining 18 cases
      (mean smoking history of 53 pack-years) showed interstitial fibrosis that was
      judged to be most consistent with smoking-associated pulmonary fibrosis. We
      conclude that the clinical diagnosis of mild asbestosis cannot be reliably
      distinguished from interstitial fibrosis in heavy smokers. 

PMID- 25565799
TI  - Continuing to Confront COPD International Physician Survey: physician knowledge
      and application of COPD management guidelines in 12 countries.
AB  - AIM: Utilizing data from the Continuing to Confront COPD (chronic obstructive
      pulmonary disease) International Physician Survey, this study aimed to describe
      physicians' knowledge and application of the GOLD (Global initiative for chronic
      Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and
      Prevention of COPD diagnosis and treatment recommendations and compare
      performance between primary care physicians (PCPs) and respiratory specialists.
      MATERIALS AND METHODS: Physicians from 12 countries were sampled from in-country
      professional databases; 1,307 physicians (PCP to respiratory specialist ratio
      three to one) who regularly consult with COPD, emphysema, or chronic bronchitis
      patients were interviewed online, by telephone or face to face. Physicians were
      questioned about COPD risk factors, prognosis, diagnosis, and treatment,
      including knowledge and application of the GOLD global strategy using patient
      scenarios. RESULTS: Physicians reported using spirometry routinely (PCPs 82%,
      respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included
      validated patient-reported outcome measures (PCPs 67%, respiratory specialists
      81%; P<0.001). Respiratory specialists were more likely than PCPs to report
      awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when
      presented with patient scenarios, they did not always perform better than PCPs
      with regard to recommending GOLD-concordant treatment options. The proportion of
      PCPs and respiratory specialists providing first- or second-choice treatment
      options concordant with GOLD strategy for a GOLD B-type patient was 38% versus
      67%, respectively. For GOLD C and D-type patients, the concordant proportions for
      PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%,
      respectively. CONCLUSION: This survey of physicians in 12 countries practicing in
      the primary care and respiratory specialty settings showed high awareness of COPD
      management guidelines. Frequent use of guideline-recommended COPD diagnostic
      practices was reported; however, gaps in the application of COPD-treatment
      recommendations were observed, warranting further evaluation to understand
      potential barriers to adopt guideline recommendations.

PMID- 25565801
TI  - Essential components of a successful doctoral program in nanomedicine.
AB  - The Nanomedicine program at Northeastern University provides a unique
      interdisciplinary graduate education that combines experiential research,
      didactic learning, networking, and outreach. Students are taught how to apply
      nanoscience and nanotechnology to problems in medicine, translate basic research
      to the development of marketable products, negotiate ethical and social issues
      related to nanomedicine, and develop a strong sense of community involvement
      within a global perspective. Since 2006, the program has recruited 50 doctoral
      students from ten traditional science, technology, and engineering disciplines to
      participate in the 2-year specialization program. Each trainee received mentoring
      from two or more individuals, including faculty members outside the student's
      home department and faculty members at other academic institutions, and/or
      clinicians. Both students and faculty members reported a significant increase in
      interdisciplinary scholarly activities, including publications, presentations,
      and funded research proposals, as a direct result of the program. Nearly 90% of
      students graduating with a specialization in nanomedicine have continued on to
      careers in the health care sector. Currently, 43% of graduates are performing
      research or developing products that directly involve nanomedicine. This article
      identifies some key elements of the Nanomedicine program, describes how they were
      implemented, and reports on the metrics of success. 

PMID- 25565800
TI  - Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles
      via the NF-kappaB signaling pathway.
AB  - Previous studies have indicated that the nephrotoxicity induced by mesoporous
      silica nanoparticles (MSNs) is closely related to inflammation. Nuclear factor
      kappa B (NF-kappaB), a common rapid transcription factor associated with
      inflammation, plays an important role in the process of many kidney diseases.
      Acute toxicity assessment with a high-dose exposure is critical for the
      development of nanoparticle, as a part of standardized procedures for the
      evaluation of their toxicity. The present study was undertaken to observe the
      acute toxicity, predict the potential target organs of MSNs injury, and test the
      hypothesis that the NF-kappaB pathway plays a role in mediating the acute kidney
      injury and renal interstitial fibrosis in mice induced by MSNs. Balb/c mice were
      intraperitoneally injected with MSNs at concentrations of 150, 300, or 600 mg/kg.
      All of the animals were euthanized 2 and 12 days after exposure, and the blood
      and kidney tissues were collected for further studies. In vitro, the
      cytotoxicity, fibrosis markers, and NF-kappaB pathway were measured in a normal
      rat kidney cell line (NRK-52E). Acute kidney injury was induced by MSNs in mice
      after 2 days, some renal tubules regenerated and renal interstitial fibrosis was
      also observed. The expression of fibrosis markers and the nuclear translocation
      of NF-kappaB p65 in the kidney homogenates increased after exposure to MSNs. The
      in vitro study showed that MSNs cause cytotoxicity in NRK-52E cells and increased
      the expression of fibrosis markers. In addition, the NF-kappaB pathway could be
      induced, and inhibition of the NF-kappaB pathway could alleviate the fibrosis
      caused by MSNs. We conclude that inflammation is a major effector of the acute
      kidney toxicity induced by MSNs and results in renal interstitial fibrosis, which
      is mediated by the NF-kappaB signaling pathway. 

PMID- 25565802
TI  - Potential anticancer properties of bioactive compounds of Gymnema sylvestre and
      its biofunctionalized silver nanoparticles.
AB  - BACKGROUND: Gymnema sylvestre is an ethno-pharmacologically important medicinal
      plant used in many polyherbal formulations for its potential health benefits.
      Silver nanoparticles (SNPs) were biofunctionalized using aqueous leaf extracts of
      G. sylvestre. The anticancer properties of the bioactive compounds and the
      biofunctionalized SNPs were compared using the HT29 human adenoma colon cancer
      cell line. METHODS: The preliminary phytochemical screening for bioactive
      compounds from aqueous extracts revealed the presence of alkaloids, triterpenes,
      flavonoids, steroids, and saponins. Biofunctionalized SNPs were synthesized using
      silver nitrate and characterized by ultraviolet-visible spectroscopy, scanning
      electron microscopy, energy-dispersive X-ray analysis, Fourier transform infrared
      spectroscopy, and X-ray diffraction for size and shape. The characterized
      biofunctionalized G. sylvestre were tested for its in vitro anticancer activity
      against HT29 human colon adenocarcinoma cells. RESULTS: The biofunctionlized G.
      sylvestre SNPs showed the surface plasmon resonance band at 430 nm. The scanning
      electron microscopy images showed the presence of spherical nanoparticles of
      various sizes, which were further determined using the Scherrer equation. In
      vitro cytotoxic activity of the biofunctionalized green-synthesized SNPs (GSNPs)
      indicated that the sensitivity of HT29 human colon adenocarcinoma cells for
      cytotoxic drugs is higher than that of Vero cell line for the same cytotoxic
      agents and also higher than the bioactive compound of the aqueous extract.
      CONCLUSION: Our results show that the anticancer properties of the bioactive
      compounds of G. sylvestre can be enhanced through biofunctionalizing the SNPs
      using the bioactive compounds present in the plant extract without compromising
      their medicinal properties.

PMID- 25565803
TI  - Activation of Schwann cells in vitro by magnetic nanocomposites via applied
      magnetic field.
AB  - Schwann cells (SCs) are attractive seed cells in neural tissue engineering, but
      their application is limited by attenuated biological activities and impaired
      functions with aging. Therefore, it is important to explore an approach to
      enhance the viability and biological properties of SCs. In the present study, a
      magnetic composite made of magnetically responsive magnetic nanoparticles (MNPs)
      and a biodegradable chitosan-glycerophosphate polymer were prepared and
      characterized. It was further explored whether such magnetic nanocomposites via
      applied magnetic fields would regulate SC biological activities. The
      magnetization of the magnetic nanocomposite was measured by a vibrating sample
      magnetometer. The compositional characterization of the magnetic nanocomposite
      was examined by Fourier-transform infrared and X-ray diffraction. The tolerance
      of SCs to the magnetic fields was tested by flow-cytometry assay. The
      proliferation of cells was examined by a 5-ethynyl-2-deoxyuridine-labeling assay,
      a PrestoBlue assay, and a Live/Dead assay. Messenger ribonucleic acid of BDNF,
      GDNF, NT-3, and VEGF in SCs was assayed by quantitative real-time polymerase
      chain reaction. The amount of BDNF, GDNF, NT-3, and VEGF secreted from SCs was
      determined by enzyme-linked immunosorbent assay. It was found that magnetic
      nanocomposites containing 10% MNPs showed a cross-section diameter of 32.33+/
      1.81 um, porosity of 80.41%+/-0.72%, and magnetization of 5.691 emu/g at 8 kOe.
      The 10% MNP magnetic nanocomposites were able to support cell adhesion and
      spreading and further promote proliferation of SCs under magnetic field exposure.
      Interestingly, a magnetic field applied through the 10% MNP magnetic scaffold
      significantly increased the gene expression and protein secretion of BDNF, GDNF,
      NT-3, and VEGF. This work is the first stage in our understanding of how to
      precisely regulate the viability and biological properties of SCs in tissue
      engineering grafts, which combined with additional molecular factors may lead to
      the development of new nerve grafts. 

PMID- 25565804
TI  - Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer
      early detection using magnetic resonance imaging.
AB  - Early cancer detection is a major factor in the reduction of mortality and cancer
      management cost. Here we developed a smart and targeted micelle-based contrast
      agent for magnetic resonance imaging (MRI), able to turn on its imaging
      capability in the presence of acidic cancer tissues. This smart contrast agent
      consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock
      copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate)), loaded with a
      gadolinium hydrophobic complex ((t)BuBipyGd) and exploits the acidic pH in cancer
      tissues. In vitro MRI experiments showed that (t)BuBipyGd-loaded micelles were pH
      sensitive, as they turned on their imaging capability only in an acidic
      microenvironment. The micelle-targeting ability toward cancer cells was enhanced
      by conjugation with an antibody against the MUC1 protein. The ability of our
      antibody-decorated micelles to be switched on in acidic microenvironments and to
      target cancer cells expressing specific antigens, together with its high Gd(III)
      content and its small size (35-40 nm) reveals their potential use for early
      cancer detection by MRI.

PMID- 25565805
TI  - Detection of Mycobacterium tuberculosis based on H37R(v) binding peptides using
      surface functionalized magnetic microspheres coupled with quantum dots - a nano
      detection method for Mycobacterium tuberculosis.
AB  - Despite suffering from the major disadvantage of low sensitivity, microscopy of
      direct smear with the Ziehl-Neelsen stain is still broadly used for detection of
      acid-fast bacilli and diagnosis of tuberculosis. Here, we present a unique
      detection method of Mycobacterium tuberculosis (MTB) using surface functionalized
      magnetic microspheres (MMSs) coupled with quantum dots (QDs), conjugated with
      various antibodies and phage display-derived peptides. The principle is based
      upon the conformation of the sandwich complex composed of bacterial cells, MMSs,
      and QDs. The complex system is tagged with QDs for providing the fluorescent
      signal as part of the detection while magnetic separation is achieved by MMSs.
      The peptide ligand H8 derived from the phage display library Ph.D.-7 is developed
      for MTB cells. Using the combinations of MMS-polyclonal antibody+QD-H8 and MMS
      H8+QD-H8, a strong signal of 10(3) colony forming units (CFU)/mL H37R(v) was
      obtained with improved specificity. MS-H8+QD-H8 combination was further optimized
      by adjusting the concentrations of MMSs, QDs, and incubation time for the maximum
      detection signal. The limit of detection for MTB was found to reach 10(3) CFU/mL
      even for the sputum matrices. Positive sputum samples could be distinguished from
      control. Thus, this novel method is shown to improve the detection limit and
      specificity of MTB from the sputum samples, and to reduce the testing time for
      accurate diagnosis of tuberculosis, which needs further confirmation of more
      clinical samples.

PMID- 25565806
TI  - Understanding greater cardiomyocyte functions on aligned compared to random
      carbon nanofibers in PLGA.
AB  - Previous studies have demonstrated greater cardiomyocyte density on carbon
      nanofibers (CNFs) aligned (compared to randomly oriented) in poly(lactic-co
      glycolic acid) (PLGA) composites. Although such studies demonstrated a closer
      mimicking of anisotropic electrical and mechanical properties for such aligned
      (compared to randomly oriented) CNFs in PLGA composites, the objective of the
      present in vitro study was to elucidate a deeper mechanistic understanding of how
      cardiomyocyte densities recognize such materials to respond more favorably.
      Results showed lower wettability (greater hydrophobicity) of CNFs embedded in
      PLGA compared to pure PLGA, thus providing evidence of selectively lower
      wettability in aligned CNF regions. Furthermore, the results correlated these
      changes in hydrophobicity with increased adsorption of fibronectin, laminin, and
      vitronectin (all proteins known to increase cardiomyocyte adhesion and functions)
      on CNFs in PLGA compared to pure PLGA, thus providing evidence of selective
      initial protein adsorption cues on such CNF regions to promote cardiomyocyte
      adhesion and growth. Lastly, results of the present in vitro study further
      confirmed increased cardiomyocyte functions by demonstrating greater expression
      of important cardiomyocyte biomarkers (such as Troponin-T, Connexin-43, and alpha
      sarcomeric actin) when CNFs were aligned compared to randomly oriented in PLGA.
      In summary, this study provided evidence that cardiomyocyte functions are
      improved on CNFs aligned in PLGA compared to randomly oriented in PLGA since CNFs
      are more hydrophobic than PLGA and attract the adsorption of key proteins
      (fibronectin, laminin, and vironectin) that are known to promote cardiomyocyte
      adhesion and expression of important cardiomyocyte functions. Thus, future
      studies should use this knowledge to further design improved CNF:PLGA composites
      for numerous cardiovascular applications. 

PMID- 25565808
TI  - A "turn-on" fluorescent microbead sensor for detecting nitric oxide.
AB  - Nitric oxide (NO) is a messenger molecule involved in numerous physical and
      pathological processes in biological systems. Therefore, the development of a
      highly sensitive material able to detect NO in vivo is a key step in treating
      cardiovascular and a number of types of cancer-related diseases, as well as
      neurological dysfunction. Here we describe the development of a fluorescent probe
      using microbeads to enhance the fluorescence signal. Microbeads are infused with
      the fluorophore, dansyl-piperazine (Ds-pip), and quenched when the fluorophore is
      coordinated with a rhodium (Rh)-complex, ie, Rh2(AcO(-))4(Ds-pip). In contrast,
      they are able to fluoresce when the transition-metal complex is replaced by NO.
      To confirm the "on/off" mechanism for detecting NO, we investigated the
      structural molecular properties using the Fritz Haber Institute ab initio
      molecular simulations (FHI-AIMS) package. According to the binding energy
      calculation, NO molecules bind more strongly and rapidly with the Rh-core of the
      Rh-complex than with Ds-pip. This suggests that NO can bond strongly with the Rh
      core and replace Ds-pip, even though Ds-pip is already near the Rh-core. However,
      the recovery process takes longer than the quenching process because the recovery
      process needs to overcome the energy barrier for formation of the transition
      state complex, ie, NO-(AcO(-))4-(Ds-pip). Further, we confirm that the Rh-complex
      with the Ds-pip structure has too small an energy gap to give off visible light
      from the highest unoccupied molecular orbital/lowest unoccupied molecular orbital
      energy level. 

PMID- 25565807
TI  - Effect of the protein corona on nanoparticles for modulating cytotoxicity and
      immunotoxicity.
AB  - Although the cytotoxicity of nanoparticles (NPs) is greatly influenced by their
      interactions with blood proteins, toxic effects resulting from blood interactions
      are often ignored in the development and use of nanostructured biomaterials for
      in vivo applications. Protein coronas created during the initial reaction with
      NPs can determine the subsequent immunological cascade, and protein coronas
      formed on NPs can either stimulate or mitigate the immune response. Along these
      lines, the understanding of NP-protein corona formation in terms of
      physiochemical surface properties of the NPs and NP interactions with the immune
      system components in blood is an essential step for evaluating NP toxicity for in
      vivo therapeutics. This article reviews the most recent developments in NP-based
      protein coronas through the modification of NP surface properties and discusses
      the associated immune responses. 

PMID- 25565809
TI  - Photo activation of HPPH encapsulated in "Pocket" liposomes triggers multiple
      drug release and tumor cell killing in mouse breast cancer xenografts.
AB  - We recently reported laser-triggered release of photosensitive compounds from
      liposomes containing dipalmitoylphosphatidylcholine (DPPC) and 1,2 bis(tricosa
      10,12-diynoyl)-sn-glycero-3-phosphocholine (DC(8,9)PC). We hypothesized that the
      permeation of photoactivated compounds occurs through domains of enhanced
      fluidity in the liposome membrane and have thus called them "Pocket" liposomes.
      In this study we have encapsulated the red light activatable anticancer
      photodynamic therapy drug 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)
      (Ex/Em410/670 nm) together with calcein (Ex/Em490/517 nm) as a marker for drug
      release in Pocket liposomes. A mole ratio of 7.6:1 lipid:HPPH was found to be
      optimal, with >80% of HPPH being included in the liposomes. Exposure of liposomes
      with a cw-diode 660 nm laser (90 mW, 0-5 minutes) resulted in calcein release
      only when HPPH was included in the liposomes. Further analysis of the quenching
      ratios of liposome-entrapped calcein in the laser treated samples indicated that
      the laser-triggered release occurred via the graded mechanism. In vitro studies
      with MDA-MB-231-LM2 breast cancer cell line showed significant cell killing upon
      treatment of cell-liposome suspensions with the laser. To assess in vivo
      efficacy, we implanted MDA-MB-231-LM2 cells containing the luciferase gene along
      the mammary fat pads on the ribcage of mice. For biodistribution experiments,
      trace amounts of a near infrared lipid probe DiR (Ex/Em745/840 nm) were included
      in the liposomes. Liposomes were injected intravenously and laser treatments (90
      mW, 0.9 cm diameter, for an exposure duration ranging from 5-8 minutes) were done
      4 hours postinjection (only one tumor per mouse was treated, keeping the second
      flank tumor as control). Calcein release occurred as indicated by an increase in
      calcein fluorescence from laser treated tumors only. The animals were observed
      for up to 15 days postinjection and tumor volume and luciferase expression was
      measured. A significant decrease in luciferase expression and reduction in tumor
      volume was observed only in laser treated animal groups injected with liposomes
      containing HPPH. Histopathological examination of tumor tissues indicated tumor
      necrosis resulting from laser treatment of the HPPH-encapsulated liposomes that
      were taken up into the tumor area.

PMID- 25565810
TI  - A robust and versatile signal-on fluorescence sensing strategy based on SYBR
      Green I dye and graphene oxide.
AB  - A robust and versatile signal-on fluorescence sensing strategy was developed to
      provide label-free detection of various target analytes. The strategy used SYBR
      Green I dye and graphene oxide as signal reporter and signal-to-background ratio
      enhancer, respectively. Multidrug resistance protein 1 (MDR1) gene and mercury
      ion (Hg(2+)) were selected as target analytes to investigate the generality of
      the method. The linear relationship and specificity of the detections showed that
      the sensitive and selective analyses of target analytes could be achieved by the
      proposed strategy with low detection limits of 0.5 and 2.2 nM for MDR1 gene and
      Hg(2+), respectively. Moreover, the strategy was used to detect real samples.
      Analytical results of MDR1 gene in the serum indicated that the developed method
      is a promising alternative approach for real applications in complex systems.
      Furthermore, the recovery of the proposed method for Hg(2+) detection was
      acceptable. Thus, the developed label-free signal-on fluorescence sensing
      strategy exhibited excellent universality, sensitivity, and handling convenience.

PMID- 25565811
TI  - Magnetic single-walled carbon nanotubes as efficient drug delivery nanocarriers
      in breast cancer murine model: noninvasive monitoring using diffusion-weighted
      magnetic resonance imaging as sensitive imaging biomarker.
AB  - PURPOSE: Targeting doxorubicin (DOX) by means of single-walled carbon nanotube
      (SWCNT) nanocarriers may help improve the clinical utility of this highly active
      therapeutic agent. Active targeting of SWCNTs using tumor-specific antibody and
      magnetic attraction by tagging the nanotubes with iron oxide nanoparticles can
      potentially reduce the unnecessary side effects and provide enhanced
      theranostics. In the current study, the in vitro and in vivo efficacy of DOX
      loaded SWCNTs as theranostic nanoprobes was evaluated in a murine breast cancer
      model. METHODS: Iron-tagged SWCNTs conjugated with Endoglin/CD105 antibody with
      or without DOX were synthetized and extensively characterized. Their
      biocompatibility was assessed in vitro in luciferase (Luc2)-expressing 4T1 (4T1
      Luc2) murine breast cancer cells using TiterTACSTM Colorimetric Apoptosis
      Detection Kit (apoptosis induction), poly (ADP-ribose) polymerase (marker for DNA
      damage), and thiobarbituric acid-reactive substances (oxidative stress
      generation) assays, and the efficacy of DOX-loaded SWCNTs was evaluated by
      measuring the radiance efficiency using bioluminescence imaging (BLI). Tumor
      progression and growth were monitored after 4T1-Luc2 cells inoculation using
      noninvasive BLI and magnetic resonance imaging (MRI) before and after subsequent
      injection of SWCNT complexes actively and magnetically targeted to tumor sites.
      RESULTS: Significant increases in apoptosis, DNA damage, and oxidative stress
      were induced by DOX-loaded SWCNTs. In addition, a tremendous decrease in
      bioluminescence was observed in a dose- and time-dependent manner. Noninvasive
      BLI and MRI revealed successful tumor growth and subsequent attenuation along
      with metastasis inhibition following DOX-loaded SWCNTs injection. Magnetic
      tagging of SWCNTs was found to produce significant discrepancies in apparent
      diffusion coefficient values providing a higher contrast to detect treatment
      induced variations as noninvasive imaging biomarker. In addition, it allowed
      their sensitive noninvasive diagnosis using susceptibility-weighted MRI and their
      magnetic targeting using an externally applied magnet. CONCLUSION: Enhanced
      therapeutic efficacy of DOX delivered through antibody-conjugated magnetic SWCNTs
      was achieved. Further, the superiority of apparent diffusion coefficient
      measurements using diffusion-weighted MRI was found to be a sensitive imaging
      biomarker for assessment of treatment-induced changes.

PMID- 25565812
TI  - Formulation and evaluation of a topical niosomal gel containing a combination of
      benzoyl peroxide and tretinoin for antiacne activity.
AB  - A skin disease, like acne, is very common and normally happens to everyone at
      least once in their lifetime. The structure of the stratum corneum is often
      compared with a brick wall, with corneocytes surrounded by the mortar of the
      intercellular lipid lamellae. One of the best options for successful drug
      delivery to the affected area of skin is the use of elastic vesicles (niosomes)
      which can be transported through the skin through channel-like structures. In
      this study, a combination of tretinoin (keratolytic agent) and benzoyl peroxide
      (BPO) (a potent antibacterial) was given by using niosomes as promising carriers
      for the effective treatment of acne by acting on a pathogenic site. In this
      section, niosomal gel formulation encapsulated drugs have been evaluated for in
      vitro, ex vivo, and in vivo, for their predetermined characteristics; and finally
      the stability of the niosome gel was tested at different temperature conditions
      for understanding of the storage conditions required for maintaining the quality
      of formulation attributes. The prepared niosome was found to be in the range of
      531 nm with a zeta potential of -43 mV; the entrapment efficiencies of tretinoin
      (TRA) and BPO niosomes were found to be 96.25%+/-0.56% and 98.75%+/-1.25%,
      respectively. The permeated amount of TRA and BPO from the niosomal gel after 24
      hours was calculated as 6.25+/-0.14 MUg/cm(2) and 5.04+/-0.014 MUg/cm(2),
      respectively. A comparative drug retention study in Wistar rat skin using cream,
      an alcoholic solution, and a niosomal gel showed 11.54 MUg, 2.68 MUg, and 15.54
      MUg amounts of TRA and 68.85 MUg, 59.98 MUg, and 143.78 MUg amounts of BPO were
      retained in the layers of skin, respectively. In vivo studies of the niosomal gel
      and antiacne cream of TRA and BPO showed that the niosomal gel was more
      efficacious than the antiacne cream because niosomal gels with a 4.16-fold lower
      dose of BPO provided the same therapeutic index at targeted sites in comparison
      to the antiacne cream. 

PMID- 25565813
TI  - Effect of silica and gold nanoparticles on macrophage proliferation, activation
      markers, cytokine production, and phagocytosis in vitro.
AB  - The accumulation of durable nanoparticles (NPs) in macrophages following systemic
      administration is well described. The ultimate biological impact of this
      accumulation on macrophage function, however, is not fully understood. In this
      study, nontoxic doses of two durable NPs, SiO2 and Au, at particle sizes of ~10
      nm and 300 nm were used to evaluate the effect of bioaccumulation on macrophage
      function in vitro using RAW 264.7 mouse macrophage-like cells as a model system.
      Cell proliferation, cell cycle, cytokine production, surface marker activation,
      and phagocytosis responses were evaluated through a panel of assays using flow
      cytometry and confocal microscopy. The most dramatic change in RAW 264.7 cell
      function was a reduction in phagocytosis as monitored by the uptake of
      Escherichia coli. Cells exposed to both 10 nm Au NPs and 10 nm SiO2 NPs showed
      ~50% decrease in phagocytosis, while the larger NPs caused a less dramatic
      reduction. In addition to modifying phagocytosis profiles, 10 nm SiO2 NPs caused
      changes in proliferation, cell cycle, and cell morphology. Au NPs had no effect
      on cell cycle, cytokine production, or surface markers and caused interference in
      phagocytosis in the form of quenching when the assay was performed via flow
      cytometry. Confocal microscopy analysis was used to minimize this interference
      and demonstrated that both sizes of Au NPs decreased the phagocytosis of E. coli.
      Overall, our results demonstrate that Au and SiO2 NP uptake by macrophages can
      influence macrophage phagocytosis in vitro without altering surface markers and
      cytokine production in vitro. While the biological impact of these findings
      remains unclear, our results indicate that bioaccumulation of durable NPs within
      the macrophages may lead to a suppression of bacterial uptake and possibly impair
      bactericidal activity. 

PMID- 25565814
TI  - Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells
      by modulating the Beclin 1/Bcl-2/VPS34 complex.
AB  - Magnetic iron oxide nanoparticles (NPs) are emerging as novel materials with
      great potentials for various biomedical applications, but their biological
      activities are largely unknown. In the present study, we found that ferroferric
      oxide nanoparticles (Fe3O4 NPs) induced autophagy in blood cells. Both naked and
      modified Fe3O4 NPs induced LC3 lipidation and degraded p62, a monitor of
      autophagy flux. And this change could be abolished by autophagy inhibitors.
      Mechanistically, Fe3O4 NP-induced autophagy was accompanied by increased Beclin 1
      and VPS34 and decreased Bcl-2, thus promoting the formation of the critical
      complex in autophagy initiation. Further studies demonstrated that Fe3O4 NPs
      attenuated cell death induced by anticancer drugs bortezomib and doxorubicin.
      Therefore, this study suggested that Fe3O4 NPs can induce prosurvival autophagy
      in blood cells by modulating the Beclin l/Bcl-2/VPS34 complex. This study
      suggests that caution should be taken when Fe3O4 NPs are used in blood cancer
      patients. 

PMID- 25565815
TI  - Novel conductive polypyrrole/zinc oxide/chitosan bionanocomposite: synthesis,
      characterization, antioxidant, and antibacterial activities.
AB  - An antibacterial and conductive bionanocomposite (BNC) film consisting of
      polypyrrole (Ppy), zinc oxide (ZnO) nanoparticles (NPs), and chitosan (CS) was
      electrochemically synthesized on indium tin oxide (ITO) glass substrate by
      electrooxidation of 0.1 M pyrrole in aqueous solution containing appropriate
      amounts of ZnO NPs uniformly dispersed in CS. This method enables the room
      temperature electrosynthesis of BNC film consisting of ZnO NPs incorporated
      within the growing Ppy/CS composite. The morphology of Ppy/ZnO/CS BNC was
      characterized by scanning electron microscopy. ITO-Ppy/CS and ITO-Ppy/ZnO/CS
      bioelectrodes were characterized using the Fourier transform infrared technique,
      X-ray diffraction, and thermogravimetric analysis. The electrical conductivity of
      nanocomposites was investigated by a four-probe method. The prepared
      nanocomposites were analyzed for antioxidant activity using the 2,2-diphenyl-1
      picrylhydrazyl assay. The results demonstrated that the antioxidant activity of
      nanocomposites increased remarkably by addition of ZnO NPs. The electrical
      conductivity of films showed a sudden decrease for lower weight ratios of ZnO NPs
      (5 wt%), while it was increased gradually for higher ratios (10, 15, and 20 wt%).
      The nanocomposites were analyzed for antibacterial activity against Gram-positive
      and Gram-negative bacteria. The results indicated that the synthesized BNC is
      effective against all of the studied bacteria, and its effectiveness is higher
      for Pseudomonas aeruginosa. The thermal stability and physical properties of BNC
      films were increased by an increase in the weight ratio of ZnO NPs, promising
      novel applications for the electrically conductive polysaccharide-based
      nanocomposites, particularly those that may exploit the antimicrobial nature of
      Ppy/ZnO/CS BNCs. 

PMID- 25565816
TI  - Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit
      protective virus neutralizing titers and cell-mediated immunity.
AB  - H5N1 avian influenza is a significant global concern with the potential to become
      the next pandemic threat. Recombinant subunit vaccines are an attractive
      alternative for pandemic vaccines compared to traditional vaccine technologies.
      In particular, polyanhydride nanoparticles encapsulating subunit proteins have
      been shown to enhance humoral and cell-mediated immunity and provide protection
      upon lethal challenge. In this work, a recombinant H5 hemagglutinin trimer (H53)
      was produced and encapsulated into polyanhydride nanoparticles. The studies
      performed indicated that the recombinant H53 antigen was a robust immunogen.
      Immunizing mice with H53 encapsulated into polyanhydride nanoparticles induced
      high neutralizing antibody titers and enhanced CD4(+) T cell recall responses in
      mice. Finally, the H53-based polyanhydride nanovaccine induced protective
      immunity against a low-pathogenic H5N1 viral challenge. Informatics analyses
      indicated that mice receiving the nanovaccine formulations and subsequently
      challenged with virus were similar to naive mice that were not challenged. The
      current studies provide a basis to further exploit the advantages of
      polyanhydride nanovaccines in pandemic scenarios.

PMID- 25565817
TI  - Nanoparticles inhibit cancer cell invasion and enhance antitumor efficiency by
      targeted drug delivery via cell surface-related GRP78.
AB  - Nanoparticles (NPs) which target specific agents could effectively recognize the
      target cells and increase the stability of chemical agents by encapsulation. As
      such, NPs have been widely used in cancer treatment research. Recently, over 90%
      of treatment failure cases in patients with metastatic cancer were attributed to
      resistance to chemotherapy. Surface-exposed glucose-regulated protein of 78 kDa
      (GRP78) is expressed highly on many tumor cell surfaces in many human cancers and
      is related to the regulation of invasion and metastasis. Herein, we report that
      NPs conjugated with antibody against GRP78 (mAb GRP78-NPs) inhibit the adhesion,
      invasion, and metastasis of hepatocellular carcinoma (HCC) and promote drug
      delivery of 5-fluorouracil into GRP78 high-expressed human hepatocellular
      carcinoma cells. Our new findings suggest that mAb GRP78-NPs could enhance drug
      accumulation by effectively transporting NPs into cell surface GRP78
      overexpressed human hepatocellular carcinoma cells and then inhibit cell
      proliferation and viability and induce cell apoptosis by regulating caspase-3. In
      brief, mAb GRP78-NPs effectively inhibit cancer cell invasion and enhance
      antitumor efficiency by targeted drug delivery. 

PMID- 25565818
TI  - Codelivery of doxorubicin and curcumin with lipid nanoparticles results in
      improved efficacy of chemotherapy in liver cancer.
AB  - Liver cancer is a leading cause of cancer deaths worldwide. The combination
      therapy of cytotoxic and chemosensitizing agents loaded in nanoparticles has been
      highlighted as an effective treatment for different cancers. However, such
      studies in liver cancer remain very limited. In our study, we aim to develop a
      novel lipid nanoparticles loaded with doxorubicin (DOX) (an effective drug for
      liver cancer) and curcumin (Cur) (a chemosensitizer) simultaneously, and we
      examined the efficacy of chemotherapy in liver cancer. DOX and Cur codelivery
      lipid nanoparticles (DOX/Cur-NPs) were successfully prepared using a high
      pressure microfluidics technique, showing a mean particle size of around 90 nm, a
      polydispersity index <0.3, and a zeta potential <-10 mV. The encapsulation
      efficacy was >90% for both DOX and Cur. The blank lipid nanoparticles were
      nontoxic, as determined by a cell cytotoxicity study in human normal liver cells
      L02 and liver cancer cells HepG2. In vitro DOX release studies revealed a
      sustained-release pattern until 48 hours in DOX/Cur-NPs. We found enhanced
      cytotoxicity and decreased inhibitory concentration (IC)50 in HepG2 cells and
      reduced cytotoxicity in L02 cells treated with DOX/Cur-NPs, suggesting the
      synergistic effects of DOX/Cur-NPs compared with free DOX and DOX nanoparticles
      (NPs). The optimal weight ratio of DOX and Cur was 1:1. Annexin-V-fluorescein
      isothiocyanate/propidium iodide double staining showed enhanced apoptosis in
      HepG2 cells treated with DOX/Cur-NPs compared with free DOX and DOX-NPs. An in
      vivo experiment showed the synergistic effect of DOX/Cur-NPs compared with DOX
      NPs on liver tumor growth inhibition. Taken together, the simultaneous delivery
      of DOX and Cur by DOX/Cur-NPs might be a promising treatment for liver cancer. 

PMID- 25565820
TI  - Safety assessment of silica and zinc oxide nanoparticles.

PMID- 25565819
TI  - Photothermal cancer therapy using graphitic carbon-coated magnetic particles
      prepared by one-pot synthesis.
AB  - We describe here a simple synthetic strategy for the fabrication of carbon-coated
      Fe3O4 (Fe3O4@C) particles using a single-component precursor, iron (III)
      diethylenetriaminepentaacetic acid complex. Physicochemical analyses revealed
      that the core of the synthesized particles consists of ferromagnetic Fe3O4
      material ranging several hundred nanometers, embedded in nitrogen-doped graphitic
      carbon with a thickness of ~120 nm. Because of their photothermal activity
      (absorption of near-infrared [NIR] light), the Fe3O4@C particles have been
      investigated for photothermal therapeutic applications. An example of one such
      application would be the use of Fe3O4@C particles in human adenocarcinoma A549
      cells by means of NIR-triggered cell death. In this system, the Fe3O4@C can
      rapidly generate heat, causing >98% cell death within 10 minutes under 808 nm NIR
      laser irradiation (2.3 W cm(-2)). These Fe3O4@C particles provided a superior
      photothermal therapeutic effect by intratumoral delivery and NIR irradiation of
      tumor xenografts. These results demonstrate that one-pot synthesis of carbon
      coated magnetic particles could provide promising materials for future clinical
      applications and encourage further investigation of this simple method. 

PMID- 25565821
TI  - Organization of research team for nano-associated safety assessment in effort to
      study nanotoxicology of zinc oxide and silica nanoparticles.
AB  - Currently, products made with nanomaterials are used widely, especially in
      biology, bio-technologies, and medical areas. However, limited investigations on
      potential toxicities of nanomaterials are available. Hence, diverse and systemic
      toxicological data with new methods for nanomaterials are needed. In order to
      investigate the nanotoxicology of nanoparticles (NPs), the Research Team for Nano
      Associated Safety Assessment (RT-NASA) was organized in three parts and launched.
      Each part focused on different contents of research directions: investigators in
      part I were responsible for the efficient management and international
      cooperation on nano-safety studies; investigators in part II performed the
      toxicity evaluations on target organs such as assessment of genotoxicity,
      immunotoxicity, or skin penetration; and investigators in part III evaluated the
      toxicokinetics of NPs with newly developed techniques for toxicokinetic analyses
      and methods for estimating nanotoxicity. The RT-NASA study was carried out in six
      steps: need assessment, physicochemical property, toxicity evaluation,
      toxicokinetics, peer review, and risk communication. During the need assessment
      step, consumer responses were analyzed based on sex, age, education level, and
      household income. Different sizes of zinc oxide and silica NPs were purchased and
      coated with citrate, L-serine, and L-arginine in order to modify surface charges
      (eight different NPs), and each of the NPs were characterized by various
      techniques, for example, zeta potentials, scanning electron microscopy, and
      transmission electron microscopy. Evaluation of the "no observed adverse effect
      level" and systemic toxicities of all NPs were performed by thorough evaluation
      steps and the toxicokinetics step, which included in vivo studies with zinc oxide
      and silica NPs. A peer review committee was organized to evaluate and verify the
      reliability of toxicity tests, and the risk communication step was also needed to
      convey the current findings to academia, industry, and consumers. Several
      limitations were encountered in the RT-NASA project, and they are discussed for
      consideration for improvements in future studies. 

PMID- 25565822
TI  - Interactive survey of consumer awareness of nanotechnologies and nanoparticles in
      consumer products in South Korea.
AB  - BACKGROUND: The purpose of our study was to understand consumers' risk awareness
      and need for relevant information about nanotechnology and nanoparticles
      contained in products currently being sold in Korea. METHODS: One thousand and
      seven adult consumers (aged 20-50 years) were randomly selected from all over
      South Korea between November 1 and 9, 2010. We surveyed the origin and degree of
      their concern and their need for information and education regarding
      nanomaterials. RESULTS: Analysis of the survey results showed no significant
      differences in responses by sex, age, and level of education, but significant
      differences were found in responses based on average monthly household income.
      Our research showed that consumers have vague expectations for and positive image
      of nanotechnology and nanoproducts but do not clearly understand what they are.
      In addition, we found that preparing and disseminating information to consumers
      is required in order to provide correct information about nanotechnology to the
      public. CONCLUSION: A communication system should be established among the
      multiple stakeholders involved with nanomaterials to address consumer
      expectations and concerns. Further, a safety evaluation system must be set up,
      the results of which should be processed by a reliable expert group so they can
      be disseminated to the public.

PMID- 25565823
TI  - Comparative analysis of nanotechnology awareness in consumers and experts in
      South Korea.
AB  - PURPOSE: This study examined the need for public communication about
      nanotechnologies and nanoparticles by providing a comparative analysis of the
      differences in risk awareness of nanotechnologies and nanoparticles between
      consumers and experts. METHODS: A total of 1,007 consumers and 150 experts
      participated in this study. A questionnaire was prepared examining their
      awareness of nanotechnologies and nanomaterials and their view of the necessity
      for information and education about the latest nanotechnologies and
      nanomaterials. RESULTS: Our results indicated that the expert group recognized
      that they knew more than consumers about nanotechnology and that there was a need
      for relevant education in nanotechnology and nanomaterials among consumers. We
      found that the consumer group had a more positive attitude toward nanotechnology,
      even though they did not know much about it. Moreover, the consumer group was
      inconclusive about the type of information on nanotechnology deemed necessary for
      the public, as well as the suitable party to be responsible for education and for
      delivering the information. CONCLUSION: An education and promotion program
      targeting consumers should be established to overcome the differences between
      consumers and experts in their awareness of nanotechnology. Specifically, the
      establishment of concepts for nanomaterials or nanoproducts is required
      immediately. With clear standards on nanomaterials, consumers can make informed
      decisions in selecting nanoproducts in the market.

PMID- 25565824
TI  - Surface treatment of silica nanoparticles for stable and charge-controlled
      colloidal silica.
AB  - An attempt was made to control the surface charge of colloidal silica
      nanoparticles with 20 nm and 100 nm diameters. Untreated silica nanoparticles
      were determined to be highly negatively charged and have stable hydrodynamic
      sizes in a wide pH range. To change the surface to a positively charged form,
      various coating agents, such as amine containing molecules, multivalent metal
      cation, or amino acids, were used to treat the colloidal silica nanoparticles.
      Molecules with chelating amine sites were determined to have high affinity with
      the silica surface to make agglomerations or gel-like networks. Amino acid
      coatings resulted in relatively stable silica colloids with a modified surface
      charge. Three amino acid moiety coatings (L-serine, L-histidine, and L-arginine)
      exhibited surface charge modifying efficacy of L-histidine > L-arginine > L
      serine and hydrodynamic size preservation efficacy of L-serine > L-arginine > L
      histidine. The time dependent change in L-arginine coated colloidal silica was
      investigated by measuring the pattern of the backscattered light in a
      TurbiscanTM. The results indicated that both the 20 nm and 100 nm L-arginine
      coated silica samples were fairly stable in terms of colloidal homogeneity,
      showing only slight coalescence and sedimentation. 

PMID- 25565825
TI  - Physicochemical properties of surface charge-modified ZnO nanoparticles with
      different particle sizes.
AB  - In this study, four types of standardized ZnO nanoparticles were prepared for
      assessment of their potential biological risk. Powder-phased ZnO nanoparticles
      with different particle sizes (20 nm and 100 nm) were coated with citrate or L
      serine to induce a negative or positive surface charge, respectively. The four
      types of coated ZnO nanoparticles were subjected to physicochemical evaluation
      according to the guidelines published by the Organisation for Economic
      Cooperation and Development. All four samples had a well crystallized Wurtzite
      phase, with particle sizes of ~30 nm and ~70 nm after coating with organic
      molecules. The coating agents were determined to have attached to the ZnO
      surfaces through either electrostatic interaction or partial coordination
      bonding. Electrokinetic measurements showed that the surface charges of the ZnO
      nanoparticles were successfully modified to be negative (about -40 mV) or
      positive (about +25 mV). Although all the four types of ZnO nanoparticles showed
      some agglomeration when suspended in water according to dynamic light scattering
      analysis, they had clearly distinguishable particle size and surface charge
      parameters and well defined physicochemical properties. 

PMID- 25565826
TI  - Effects of surface-modifying ligands on the colloidal stability of ZnO
      nanoparticle dispersions in in vitro cytotoxicity test media.
AB  - The extrinsic physicochemical properties of nanoparticles (NPs), such as
      hydrodynamic size, surface charge, surface functional group, and colloidal
      stabilities, in toxicity testing media are known to have a significant influence
      on in vitro toxicity assessments. Therefore, interpretation of nanotoxicity test
      results should be based on reliable characterization of the NPs' extrinsic
      properties in actual toxicity testing media. Here, we present a set of
      physicochemical characterization results for commercially available ZnO NPs,
      including core diameter, hydrodynamic diameter, surface charges, and colloidal
      stabilities, in two in vitro toxicity testing media (Roswell Park Memorial
      Institute [RPMI] and Dulbecco's Modified Eagle's Medium [DMEM]), as well as
      simple cell viability assay results for selected ZnO NPs. Four commercially
      available and manufactured ZnO NPs, with different core sizes, were used in this
      study, and their surface charge was modified with five different surface coating
      materials (sodium citrate, tris(2-aminoethyl)amine, poly(acrylic acid),
      poly(allylamine hydrochloride), and poly-L-lysine hydrochloride). The results
      showed that ZnO NPs were better dispersed in cell culture media via surface
      modification with positively or negatively charged molecules. Moreover, in the
      presence of fetal bovine serum (FBS) in RPMI and DMEM media, ZnO NPs were found
      even better dispersed for a longer period (at least 48 hours). For the HeLa cells
      exposed to ZnO NPs in DMEM media without FBS, surface charge-dependent
      cytotoxicity trends were observed, while these trends were not observed for those
      cells cultured in FBS-containing media. This confirmed the important roles of
      surface-modifying compounds and of surface charge on the resultant cytotoxicities
      of NPs. 

PMID- 25565827
TI  - Toxicity of colloidal silica nanoparticles administered orally for 90 days in
      rats.
AB  - This study was undertaken to investigate the potential toxicity and establish the
      no observed adverse effect level (NOAEL) and target organ(s) of negatively
      charged colloidal silica particles of different sizes, ie, SiO2 (EN20(-)) (20 nm)
      or SiO2 (EN100(-)) 2(100 nm), administered by gavage in Sprague-Dawley rats.
      After verification of the physicochemical properties of the SiO2 particles to be
      tested, a preliminary dose range-finding study and 90-day repeated dose study
      were conducted according to the Organisation for Economic Cooperation and
      Development test guideline. Based on the results of the 14-day dose range-finding
      study, a high dose was determined to be 2,000 mg/kg, and middle and low doses
      were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study,
      there were no animal deaths in relation to administration of SiO2 particles of
      either size. In addition, no treatment-related clinical changes or
      histopathological findings were observed in any of the experimental groups.
      Moreover, no difference in toxic effects from chronic exposure to SiO2 (EN20(
      ))(20 nm) or SiO2 (EN100(-)) (100 nm) was observed. The results of this study
      indicate that the NOAEL for SiO2 (EN20(-)) and SiO2 (EN100(-)) would most likely
      be 2,000 mg/kg, and no target organ was identified in rats of either sex. 

PMID- 25565828
TI  - A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc
      oxide nanoparticles in Sprague Dawley rats.
AB  - PURPOSE: The widespread use of nanoparticles (NPs) in industrial and biomedical
      applications has prompted growing concern regarding their potential toxicity and
      impact on human health. This study therefore investigated the subchronic,
      systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm,
      negatively charged zinc oxide (ZnO(SM20(-))) NPs in Sprague Dawley rats for 90
      days. METHODS: The high-dose NP level was set at 500 mg/kg of bodyweight, and the
      mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats
      were observed during a 14-day recovery period after the last NP administration
      for the persistence or reduction of any adverse effects. Toxicokinetic and
      distribution studies were also conducted to determine the systemic distribution
      of the NPs. RESULTS: No rats died during the test period. However, ZnO(SM20(-))
      NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted
      acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid
      cell infiltration and excessive salivation, and increased the numbers of
      regenerative acinar cells in the pancreas. In addition, stomach lesions were seen
      at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500
      mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney,
      intestines, and plasma, but not in other organs investigated. CONCLUSION: A
      ZnO(SM20(-)) NP NOAEL could not be established from the current results, but the
      lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were
      associated with a number of undesirable systemic actions. Thus, their use in
      humans must be approached with caution.

PMID- 25565829
TI  - A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc
      oxide nanoparticles in Sprague Dawley rats.
AB  - PURPOSE: The study reported here was conducted to determine the systemic oral
      toxicity and to find the no-observed-adverse-effect level of 20 nm positively
      charged zinc oxide (ZnO(SM20(+))) nanoparticles in Sprague Dawley rats for 90
      days. METHODS: For the 90-day toxicity study, the high dose was set as 500 mg per
      kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and
      125 mg/kg, respectively. The rats were held for a 14-day recovery period after
      the last administration, to observe for the persistence or reduction of any toxic
      effects. A distributional study was also carried out for the systemic
      distribution of ZnO(SM20(+)) NPs. RESULTS: No rats died during the test period.
      There were no significant clinical changes due to the test article during the
      experimental period in functional assessment, body weight, food and water
      consumption, ophthalmological testing, urine analysis, necropsy findings, or
      organ weights, but salivation was observed immediately after administration in
      both sexes. The total red blood cell count was increased, and hematocrit,
      albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin
      concentration were decreased significantly compared with control in both 500
      mg/kg groups. Total protein and albumin levels were decreased significantly in
      both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed
      acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa,
      and retinal atrophy of the eye in the 500 mg/kg group. CONCLUSION: There were
      significant parameter changes in terms of anemia in the hematological and blood
      chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change
      was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was
      not determined, but the lowest-observed-adverse-effect level was considered to be
      125 mg/kg in both sexes and the target organs were found to be the pancreas, eye,
      and stomach.

PMID- 25565830
TI  - Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral
      administration in Sprague Dawley rats.
AB  - Nanoparticles (NPs) are used commercially in health and fitness fields, but
      information about the toxicity and mechanisms underlying the toxic effects of NPs
      is still very limited. The aim of this study is to investigate the toxic
      effect(s) of 100 nm negatively (ZnO(AE100[-])) or positively (ZnO(AE100[+]))
      charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to
      establish a no observed adverse effect level, and to identify target organ(s).
      After verification of the primary particle size, morphology, hydrodynamic size,
      and zeta potential of each test article, we performed a 90-day study according to
      Organisation for Economic Co-operation and Development test guideline 408. For
      the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses
      were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant
      changes in hematological and blood biochemical analysis, which could correlate
      with anemia-related parameters, in the 500 mg/kg groups of both sexes.
      Histopathological examination showed significant adverse effects (by both test
      articles) in the stomach, pancreas, eye, and prostate gland tissues, but the
      particle charge did not affect the tendency or the degree of the lesions. We
      speculate that this inflammatory damage might result from continuous irritation
      caused by both test articles. Therefore, the target organs for both ZnO(AE100(-))
      and ZnO(AE100(+)) are considered to be the stomach, pancreas, eye, and prostate
      gland. Also, the no observed adverse effect level for both test articles was
      identified as 31.25 mg/kg for both sexes, because the adverse effects were
      observed at all doses greater than 125 mg/kg. 

PMID- 25565831
TI  - Evaluation of silica nanoparticle toxicity after topical exposure for 90 days.
AB  - Silica is a very common material that can be found in both crystalline and
      amorphous forms. Well-known toxicities of the lung can occur after exposure to
      the crystalline form of silica. However, the toxicities of the amorphous form of
      silica have not been thoroughly studied. The majority of in vivo studies of
      amorphous silica nanoparticles (NPs) were performed using an inhalation exposure
      method. Since silica NPs can be commonly administered through the skin, a study
      of dermal silica toxicity was necessary to determine any harmful effects from
      dermal exposures. The present study focused on the results of systemic toxicity
      after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance
      with the Organization for Economic Cooperation and Development test guideline 411
      with a good laboratory practice system. Unlike the inhalation route or
      gastrointestinal route, the contact of silica NPs through skin did not result in
      any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in
      rats. 

PMID- 25565832
TI  - Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats.
AB  - Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and
      can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are
      used often in sunscreens due to consumer preference over larger sizes, which
      appear opaque when dermally applied. Although the US Food and Drug Administration
      approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing
      safety concerns. The aim of this study was to evaluate the subchronic toxicity of
      ZnO NPs after dermal application according to the Organization for Economic
      Cooperation and Development Test Guidelines 411 using Good Laboratory Practice.
      Sprague Dawley rats were randomly divided into eight (one control, one vehicle
      control, three experimental, and three recovery) groups. Different concentrations
      of ZnO NPs were dermally applied to the rats in the experimental groups for 90
      days. Clinical observations as well as weight and food consumption were measured
      and recorded daily. Hematology and biochemistry parameters were determined. Gross
      pathologic and histopathologic examinations were performed on selected tissues
      from all animals. Analyses of tissue were undertaken to determine target organ
      tissue distribution. There was no increased mortality in the experimental group.
      Although there was dose-dependent irritation at the site of application, there
      were no abnormal findings related to ZnO NPs in other organs. Increased
      concentrations of ZnO in the liver, small intestine, large intestine, and feces
      were thought to result from oral ingestion of ZnO NPs via licking. Penetration of
      ZnO NPs through the skin seemed to be limited via the dermal route. This study
      demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000
      mg/kg body weight when they are applied dermally. 

PMID- 25565833
TI  - Effect of zinc oxide nanoparticles on dams and embryo-fetal development in rats.
AB  - This study investigated the potential adverse effects of zinc oxide nanoparticles
      (ZnO(SM20[-]) NPs; negatively charged, 20 nm) on pregnant dams and embryo-fetal
      development after maternal exposure over the period of gestational days 5-19 with
      Sprague Dawley rats. ZnO(SM20(-)) NPs were administered to pregnant rats by
      gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams
      were subjected to caesarean section on gestational day 20, and all the fetuses
      were examined for external, visceral, and skeletal alterations. Toxicity in the
      dams manifested as significantly decreased body weight at 400 mg/kg/day and
      decreased liver weight, and increased adrenal glands weight at 200 mg/kg/day and
      400 mg/kg/day. However, no treatment-related difference in the number of corpora
      lutea, the number of implantation sites, the implantation rate (%), resorption,
      dead fetuses, litter size, fetal deaths, fetal and placental weights, and sex
      ratio were observed between the groups. Morphological examinations of the fetuses
      demonstrated no significant difference in the incidences of abnormalities between
      the groups. No significant difference was found in the Zn content of fetal tissue
      between the control and high-dose groups. These results showed that a 15-day
      repeated oral dose of ZnO(SM20(-)) was minimally maternotoxic at dose of 200
      mg/kg/day and 400 mg/kg/day. 

PMID- 25565834
TI  - Prenatal development toxicity study of zinc oxide nanoparticles in rats.
AB  - This study investigated the potential adverse effects of zinc oxide nanoparticles
      ([ZnO(SM20(+)) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on
      pregnant dams and embryo-fetal development after maternal exposure over the
      period of gestational days 5-19 with Sprague-Dawley rats. ZnO(SM20(+)) NPs were
      administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All
      dams were subjected to a cesarean section on gestational day 20, and all of the
      fetuses were examined for external, visceral, and skeletal alterations. Toxicity
      in the dams manifested as significantly decreased body weight after
      administration of 400 mg/kg/day NPs; reduced food consumption after
      administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and
      increased adrenal glands weight after administration of 400 mg/kg/day NPs.
      However, no treatment-related difference in: number of corpora lutea; number of
      implantation sites; implantation rate (%); resorption; dead fetuses; litter size;
      fetal deaths and placental weights; and sex ratio were observed between the
      groups. On the other hand, significant decreases between treatment groups and
      controls were seen for fetal weights after administration of 400 mg/kg/day NPs.
      Morphological examinations of the fetuses demonstrated significant differences in
      incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no
      significant difference was found in the Zn content of fetal tissue between the
      control and high-dose groups. These results showed that oral doses for the study
      with 15-days repeated of ZnO(SM20(+)) NPs were maternotoxic in the 200 mg/kg/day
      group, and embryotoxic in the 400 mg/kg/day group. 

PMID- 25565835
TI  - Undetactable levels of genotoxicity of SiO2 nanoparticles in in vitro and in vivo
      tests.
AB  - BACKGROUND: Silica dioxide (SiO2) has been used in various industrial products,
      including paints and coatings, plastics, synthetic rubbers, and adhesives.
      Several studies have investigated the genotoxic effects of SiO2; however, the
      results remain controversial due to variations in the evaluation methods applied
      in determining its physicochemical properties. Thus, well characterized chemicals
      and standardized methods are needed for better assessment of the genotoxicity of
      nanoparticles. METHODS: The genotoxicity of SiO2 was evaluated using two types of
      well characterized SiO2, ie, 20 nm (-) charge (SiO (EN20(-))2) and 100 nm (-)
      charge (SiO (EN100(-))2). Four end point genotoxicity tests, ie, the bacterial
      mutation assay, in vitro chromosomal aberration test, in vivo comet assay, and in
      vivo micronucleus test, were conducted following the test guidelines of the
      Organization for Economic Cooperation and Development (OECD) with application of
      Good Laboratory Practice. RESULTS: No statistically significant differences were
      found in the bacterial mutation assay, in vitro chromosomal aberration test, in
      vivo comet assay, and in vivo micronucleus test when tested for induction of
      genotoxicity in both two types of SiO2 nanoparticles. CONCLUSION: These results
      suggest that SiO2 nanoparticles, in particular SiO2 (EN20(-)) and SiO2 (EN100(
      )), are not genotoxic in both in vitro and in vivo systems under OECD guidelines.
      Further, the results were generated in accordance with OECD test guidelines, and
      Good Laboratory Practice application; it can be accepted as reliable information
      regarding SiO2-induced genotoxicity.

PMID- 25565836
TI  - Immunotoxicity of silicon dioxide nanoparticles with different sizes and
      electrostatic charge.
AB  - Silicon dioxide (SiO2) nanoparticles (NPs) have been widely used in the
      biomedical field, such as in drug delivery and gene therapy. However, little is
      known about the biological effects and potential hazards of SiO2. Herein, the
      colloidal SiO2 NPs with two different sizes (20 nm and 100 nm) and different
      charges (L-arginine modified: SiO2 (EN20[R]), SiO2 (EN100[R]); and negative: SiO2
      (EN20[-]), SiO2 (EN100[-]) were orally administered (750 mg/kg/day) in female
      C57BL/6 mice for 14 days. Assessments of immunotoxicity include hematology
      profiling, reactive oxygen species generation and their antioxidant effect,
      stimulation assays for B- and T-lymphocytes, the activity of natural killer (NK)
      cells, and cytokine profiling. In vitro toxicity was also investigated in the RAW
      264.7 cell line. When the cellularity of mouse spleen was evaluated, there was an
      overall decrease in the proliferation of B- and T-cells for all the groups fed
      with SiO2 NPs. Specifically, the SiO2 (EN20(-)) NPs showed the most pronounced
      reduction. In addition, the nitric oxide production and NK cell activity in SiO2
      NP-fed mice were significantly suppressed. Moreover, there was a decrease in the
      serum concentration of inflammatory cytokines such as interleukin (IL)-1beta, IL
      12 (p70), IL-6, tumor necrosis factor-alpha, and interferon-gamma. To elucidate
      the cytotoxicity mechanism of SiO2 in vivo, an in vitro study using the RAW 264.7
      cell line was performed. Both the size and charge of SiO2 using murine macrophage
      RAW 264.7 cells decreased cell viability dose-dependently. Collectively, our data
      indicate that different sized and charged SiO2 NPs would cause differential
      immunotoxicity. Interestingly, the small-sized and negatively charged SiO2 NPs
      showed the most potent in vivo immunotoxicity by way of suppressing the
      proliferation of lymphocytes, depressing the killing activity of NK cells, and
      decreasing proinflammatory cytokine production, thus leading to
      immunosuppression. 

PMID- 25565837
TI  - Immunotoxicity of zinc oxide nanoparticles with different size and electrostatic
      charge.
AB  - While zinc oxide (ZnO) nanoparticles (NPs) have been recognized to have promising
      applications in biomedicine, their immunotoxicity has been inconsistent and even
      contradictory. To address this issue, we investigated whether ZnO NPs with
      different size (20 or 100 nm) and electrostatic charge (positive or negative)
      would cause immunotoxicity in vitro and in vivo, and explored their underlying
      molecular mechanism. Using Raw 264.7 cell line, we examined the immunotoxicity
      mechanism of ZnO NPs as cell viability. We found that in a cell viability assay,
      ZnO NPs with different size and charge could induce differential cytotoxicity to
      Raw 264.7 cells. Specifically, the positively charged ZnO NPs exerted higher
      cytotoxicity than the negatively charged ones. Next, to gauge systemic
      immunotoxicity, we assessed immune responses of C57BL/6 mice after oral
      administration of 750 mg/kg/day dose of ZnO NPs for 2 weeks. In parallel, ZnO NPs
      did not alter the cell-mediated immune response in mice but suppressed innate
      immunity such as natural killer cell activity. The CD4(+)/CD8(+) ratio, a marker
      for matured T-cells was slightly reduced, which implies the alteration of immune
      status induced by ZnO NPs. Accordingly, nitric oxide production from splenocyte
      culture supernatant in ZnO NP-fed mice was lower than control. Consistently,
      serum levels of pro/anti-inflammatory (interleukin [IL]-1beta, tumor necrosis
      factor-alpha, and IL-10) and T helper-1 cytokines (interferon-gamma and IL-12p70)
      in ZnO NP-fed mice were significantly suppressed. Collectively, our results
      indicate that different sized and charged ZnO NPs would cause in vitro and in
      vivo immunotoxicity, of which nature is an immunosuppression. 

PMID- 25565838
TI  - Analysis of SiO2 nanoparticles binding proteins in rat blood and brain
      homogenate.
AB  - A multitude of nanoparticles, such as titanium oxide (TiO2), zinc oxide, aluminum
      oxide, gold oxide, silver oxide, iron oxide, and silica oxide, are found in many
      chemical, cosmetic, pharmaceutical, and electronic products. Recently, SiO2
      nanoparticles were shown to have an inert toxicity profile and no association
      with an irreversible toxicological change in animal models. Hence, exposure to
      SiO2 nanoparticles is on the increase. SiO2 nanoparticles are routinely used in
      numerous materials, from strengthening filler for concrete and other construction
      composites, to nontoxic platforms for biomedical application, such as drug
      delivery and theragnostics. On the other hand, recent in vitro experiments
      indicated that SiO2 nanoparticles were cytotoxic. Therefore, we investigated
      these nanoparticles to identify potentially toxic pathways by analyzing the
      adsorbed protein corona on the surface of SiO2 nanoparticles in the blood and
      brain of the rat. Four types of SiO2 nanoparticles were chosen for investigation,
      and the protein corona of each type was analyzed using liquid chromatography
      tandem mass spectrometry technology. In total, 115 and 48 plasma proteins from
      the rat were identified as being bound to negatively charged 20 nm and 100 nm
      SiO2 nanoparticles, respectively, and 50 and 36 proteins were found for 20 nm and
      100 nm arginine-coated SiO2 nanoparticles, respectively. Higher numbers of
      proteins were adsorbed onto the 20 nm sized SiO2 nanoparticles than onto the 100
      nm sized nanoparticles regardless of charge. When proteins were compared between
      the two charges, higher numbers of proteins were found for arginine-coated
      positively charged SiO2 nanoparticles than for the negatively charged
      nanoparticles. The proteins identified as bound in the corona from SiO2
      nanoparticles were further analyzed with ClueGO, a Cytoscape plugin used in
      protein ontology and for identifying biological interaction pathways. Proteins
      bound on the surface of nanoparticles may affect functional and conformational
      properties and distributions in complicated biological processes. 

PMID- 25565839
TI  - Analysis of zinc oxide nanoparticles binding proteins in rat blood and brain
      homogenate.
AB  - Nanoparticles (NPs) are currently used in chemical, cosmetic, pharmaceutical, and
      electronic products. Nevertheless, limited safety information is available for
      many NPs, especially in terms of their interactions with various binding
      proteins, leading to potential toxic effects. Zinc oxide (ZnO) NPs are included
      in the formulation of new products, such as adhesives, batteries, ceramics,
      cosmetics, cement, glass, ointments, paints, pigments, and supplementary foods,
      resulting in increased human exposures to ZnO. Hence, we investigated the
      potential ZnO nanotoxic pathways by analyzing the adsorbed proteins, called
      protein corona, from blood and brain from four ZnO NPs, ZnO(SM20(-)),
      ZnO(SM20(+)), ZnO(AE100(-)), and ZnO(AE100(+)), in order to understand their
      potential mechanisms in vivo. Through this study, liquid chromatography-mass
      spectroscopy/mass spectroscopy technology was employed to identify all bound
      proteins. Totals of 52 and 58 plasma proteins were identified as being bound to
      ZnO(SM20(-)) and ZnO(SM20(+)), respectively. For ZnO(AE100(-)) and ZnO(AE100(+)),
      58 and 44 proteins were bound, respectively. Similar numbers of proteins were
      adsorbed onto ZnO irrespective of size or surface charge of the nanoparticle.
      These proteins were further analyzed with ClueGO, a Cytoscape plugin, which
      provided gene ontology and the biological interaction processes of identified
      proteins. Interactions between diverse proteins and ZnO nanoparticles could
      result in an alteration of their functions, conformation, and clearance,
      eventually affecting many biological processes. 

PMID- 25565840
TI  - Assessment of ZnO and SiO2 nanoparticle permeability through and toxicity to the
      blood-brain barrier using Evans blue and TEM.
AB  - As increasing variants of nanoparticles (NPs) are being used in various products,
      it has become apparent that size alone can no longer adequately explain the
      variety of generated toxic profiles. Recent studies with NPs have suggested that
      various sizes of NPs could determine in vitro toxicity. In an attempt to address
      concerns regarding neurotoxicity of zinc oxide (ZnO) and silica (SiO2) NPs, these
      were examined after exposing them via oral, dermal, and intravenous
      administrations of NPs and their toxicological effects on the brain over a
      prescribed period of time were assessed. After 28 days of repeated oral
      administrations of ZnO or SiO2 independently, possibly due to damages to the
      blood brain barrier (BBB), neurotoxicity, were investigated by Evans blue
      technique. Next, in order to assess whether ZnO NPs could compromise the BBB, ZnO
      NPs were intravenously injected on day 0, 7, 14, 21 and 28 no further treatment
      was administered for 62 days. Deposition of SiO2 in brain from repeated dermal
      and oral administrations for 90 days were evaluated by transmission electron
      microscopy coupled with scanning energy-dispersive X-ray spectroscopy.
      Physiochemical profiles were principally determined on particle size at the
      beginning of the current toxicity investigations on ZnO and SiO2 NPs. The BBB was
      found to be intact after independent repeated oral administrations of ZnO or SiO2
      NPs for 28 days, suggesting no significant damage. Neuronal death was also not
      observed after the intravenous administrations of ZnO NPs. After 90 days of
      repeated dermal and oral administration of SiO2 NPs, no deposition of NPs was
      observed in hippocampus, striatum, and cerebellum regions using transmission
      electron microscope analyses. These observations suggest that the BBB was not
      compromised and was able to block penetration of ZnO and SiO2 NPs, resulting in
      significant neurotoxic effects. Moreover, absence of SiO2 in three regions of
      brain after dermal and oral administrations for 90 days suggested that brain was
      protected from SiO2. No behavior change was observed in all studies, suggesting
      that 90 days may not be long enough to assess full neurotoxicity of NPs in vivo. 

PMID- 25565841
TI  - In vitro cytotoxicity of SiO2 or ZnO nanoparticles with different sizes and
      surface charges on U373MG human glioblastoma cells.
AB  - Silicon dioxide (SiO2) and zinc oxide (ZnO) nanoparticles are widely used in
      various applications, raising issues regarding the possible adverse effects of
      these metal oxide nanoparticles on human cells. In this study, we determined the
      cytotoxic effects of differently charged SiO2 and ZnO nanoparticles, with mean
      sizes of either 100 or 20 nm, on the U373MG human glioblastoma cell line. The
      overall cytotoxicity of ZnO nanoparticles against U373MG cells was significantly
      higher than that of SiO2 nanoparticles. Neither the size nor the surface charge
      of the ZnO nanoparticles affected their cytotoxicity against U373MG cells. The 20
      nm SiO2 nanoparticles were more toxic than the 100 nm nanoparticles against
      U373MG cells, but the surface charge had little or no effect on their
      cytotoxicity. Both SiO2 and ZnO nanoparticles activated caspase-3 and induced DNA
      fragmentation in U373MG cells, suggesting the induction of apoptosis. Thus, SiO2
      and ZnO nanoparticles appear to exert cytotoxic effects against U373MG cells,
      possibly via apoptosis. 

PMID- 25565842
TI  - Optical imaging of absorption and distribution of RITC-SiO2 nanoparticles after
      oral administration.
AB  - PURPOSE: In this study, we investigated the absorption and distribution of
      rhodamine B isothiocyanate (RITC)-incorporated silica oxide nanoparticles(SiNPs)
      (RITC-SiNPs) after oral exposure, by conducting optical imaging, with a focus on
      tracking the movement of RITC-SiNPs of different particle size and surface
      charge. METHODS: RITC-SiNPs (20 or 100 nm; positively or negatively charged) were
      used to avoid the dissociation of a fluorescent dye from nanoparticles via
      spontaneous or enzyme-catalyzed reactions in vivo. The changes in the
      nanoparticle sizes and shapes were investigated in an HCl solution for 6 hours.
      RITC-SiNPs were orally administered to healthy nude mice at a dose of 100 mg/kg.
      Optical imaging studies were performed at 2, 4, and 6 hours after oral
      administration. The mice were sacrificed at 2, 4, 6, and 10 hours post
      administration, and ex vivo imaging studies were performed. RESULTS: The RITC
      SiNPs were stable in the HCl solution for 6 hours, without dissociation of RITC
      from the nanoparticles and without changes in size and shape. RITC-SiNPs flowed
      into the small intestine from the stomach and gradually moved along the gut
      during the experiment. In the ex vivo imaging studies, optical signals were
      observed mostly in the lungs, liver, pancreas, and kidneys. The orally
      administered RITC-SiNPs, which were absorbed in the systemic circulation, were
      eliminated from the body into the urine. The 20 nm RITC-SiNPs showed higher
      uptake in the lungs than the 100 nm RITC-SiNPs. The distribution of the 100 nm
      RITC-SiNPs in the liver was higher than that of the 20 nm RITC-SiNPs, but the
      differences in the surface charge behavior were imperceptible. CONCLUSION: We
      demonstrated that the movement of RITC-SiNPs after oral exposure could be traced
      by optical imaging. Optical imaging has the potential to provide valuable
      information that will help in understanding the behavior of SiNPs in the body
      following exposure.

PMID- 25565843
TI  - Tissue distribution and excretion kinetics of orally administered silica
      nanoparticles in rats.
AB  - PURPOSE: The effects of particle size on the tissue distribution and excretion
      kinetics of silica nanoparticles and their biological fates were investigated
      following a single oral administration to male and female rats. METHODS: Silica
      nanoparticles of two different sizes (20 nm and 100 nm) were orally administered
      to male and female rats, respectively. Tissue distribution kinetics, excretion
      profiles, and fates in tissues were analyzed using elemental analysis and
      transmission electron microscopy. RESULTS: The differently sized silica
      nanoparticles mainly distributed to kidneys and liver for 3 days post
      administration and, to some extent, to lungs and spleen for 2 days post
      administration, regardless of particle size or sex. Transmission electron
      microscopy and energy dispersive spectroscopy studies in tissues demonstrated
      almost intact particles in liver, but partially decomposed particles with an
      irregular morphology were found in kidneys, especially in rats that had been
      administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent
      and the smaller 20 nm particles were found to be more rapidly eliminated than the
      larger 100 nm particles. Elimination profiles showed 7%-8% of silica
      nanoparticles were excreted via urine, but most nanoparticles were excreted via
      feces, regardless of particle size or sex. CONCLUSION: The kidneys, liver, lungs,
      and spleen were found to be the target organs of orally-administered silica
      nanoparticles in rats, and this organ distribution was not affected by particle
      size or animal sex. In vivo, silica nanoparticles were found to retain their
      particulate form, although more decomposition was observed in kidneys, especially
      for 20 nm particles. Urinary and fecal excretion pathways were determined to play
      roles in the elimination of silica nanoparticles, but 20 nm particles were
      secreted more rapidly, presumably because they are more easily decomposed. These
      findings will be of interest to those seeking to predict potential toxicological
      effects of silica nanoparticles on target organs.

PMID- 25565844
TI  - Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and
      protein interaction.
AB  - Biokinetic studies of zinc oxide (ZnO) nanoparticles involve systematic and
      quantitative analyses of absorption, distribution, metabolism, and excretion in
      plasma and tissues of whole animals after exposure. A full understanding of the
      biokinetics provides basic information about nanoparticle entry into systemic
      circulation, target organs of accumulation and toxicity, and elimination time,
      which is important for predicting the long-term toxic potential of nanoparticles.
      Biokinetic behaviors can be dependent on physicochemical properties, dissolution
      property in biological fluids, and nanoparticle-protein interaction. Moreover,
      the determination of biological fates of ZnO nanoparticles in the systemic
      circulation and tissues is critical in interpreting biokinetic behaviors and
      predicting toxicity potential as well as mechanism. This review focuses on
      physicochemical factors affecting the biokinetics of ZnO nanoparticles, in
      concert with understanding bioavailable fates and their interaction with
      proteins. 

PMID- 25565847
TI  - Asn563Ser polymorphism of CD31/PECAM-1 is associated with atherosclerotic
      cerebral infarction in a southern Han population.
AB  - BACKGROUND: CD31, also called platelet endothelial cell adhesion molecule-1
      (PECAM-1), is thought to play a role in the pathological mechanisms of
      atherosclerosis. Leu125Val polymorphism and elevated plasma levels of soluble
      PECAM-1 (sPECAM-1) were found to be associated with cerebral infarction. Our aim
      was to investigate the association between the Asn563Ser polymorphism of
      CD31/PECAM-1, plasma level of sPECAM-1, and the risk of atherosclerotic cerebral
      infarction (ACI) in the southern Han population of the People's Republic of
      China. SUBJECTS AND METHODS: A total of 147 subjects with ACI and 114 controls
      were enrolled in the study. The Asn563Ser CD31/PECAM-1 polymorphism was detected
      using the polymerase chain reaction-restriction fragment length polymorphism
      method. The plasma spECAM-1 level was measured using the enzyme-linked
      immunosorbent assay method. RESULTS: In this study, statistically significant
      differences in Asn563Ser genotype and allele distribution were found between the
      cases and controls (P<0.05). Furthermore, logistic regression analysis showed
      that the GG genotype is associated with increase in ACI risk (odds ratio =4.862,
      P<0.001). The plasma level of sPECAM-1 was associated with ACI (odds ratio
      =1.431, P=0.038). In both the ACI and the control groups, the plasma sPECAM-1
      level in subjects with the GG genotype was higher than that in subjects carrying
      the AA or GA genotype (P<0.05). CONCLUSION: Our study showed that the Asn563Ser
      polymorphism of CD31/PECAM-1 gene and elevated plasma sPECAM-1 level are related
      to ACI risk in the southern Han population of People's Republic of China.

PMID- 25565846
TI  - Exploring the risk-factor association between depression and incident stroke: a
      systematic review and meta-analysis.
AB  - There is growing evidence that depression increases the risk of incident stroke.
      However, few studies have considered possible residual confounding effects by
      preexistent cerebrovascular and cardiac diseases. Therefore, we synthesized data
      from cohort studies to explore whether depressed individuals free of
      cerebrovascular and cardiac diseases are at higher risk of incident stroke. We
      searched the electronic databases PubMed and Medline for eligible cohort studies
      that examined the prospective association between depression and first-ever
      stroke. A random-effects model was used for quantitative data synthesis.
      Sensitivity analyses comprised cohort studies that considered a lag period with
      exclusion of incident strokes in the first years of follow-up to minimize
      residual confounding by preexistent silent strokes and excluded cardiac disease
      at baseline. Overall, we identified 28 cohort studies with 681,139 participants
      and 13,436 (1.97%) incident stroke cases. The pooled risk estimate revealed an
      increased risk of incident stroke for depression (relative risk 1.40, 95%
      confidence interval [CI] 1.27-1.53; P<0.0001). When we excluded incident strokes
      that occurred in the first years of follow-up, the prospective association
      between depression and incident stroke remained significant (relative risk 1.64,
      95% CI 1.27-2.11; P<0.0001). This positive association also remained after we
      considered only studies with individuals with cardiac disease at baseline
      excluded (relative risk 1.43, 95% CI 1.19-1.72; P<0.0001). The prospective
      association of depression and increased risk of first-ever stroke demonstrated in
      this meta-analysis appears to be driven neither by preexistence of clinically
      apparent cerebrovascular and cardiovascular diseases nor by silent stroke. 

PMID- 25565848
TI  - Clinical preference for factors in treatment of geriatric depression.
AB  - Little is known about symptom preferences of clinical psychiatrists in the
      treatment of geriatric depression and preferences for avoiding adverse drug
      effects. Participants (board-certified psychiatrists) were recruited prior to a
      lecture on geriatric depression during a continuing education program. An
      analytic hierarchy process was performed and participants were asked for pairwise
      comparison of criteria guiding them in appraising therapeutic efficacy, and in
      avoiding toxicity and adverse events. Of the 61 participants from the continuing
      education program, 42 (69%) returned their data sheet. Avoidance of
      cardiotoxicity was regarded as more important than avoidance of hepatotoxicity or
      hematotoxicity. Concerning adverse events, highest preference was given to
      avoidance of falls and drug interactions, followed by avoidance of sedation,
      weight change, and impairment of sexual function. The most important preferences
      for appraisal of therapeutic efficacy were suicidality over ability to
      concentrate and sleep. Clinical psychiatrists have a hierarchy of preferences for
      treatment goals and avoidance of adverse events and toxicity. This raises the
      question for future research whether these preferences cause differences in
      prescription patterns in clinical practice even though a multitude of
      antidepressants are similarly effective when judged with instruments used in
      clinical trials. 

PMID- 25565849
TI  - Defensive function of persecutory delusion and discrepancy between explicit and
      implicit self-esteem in schizophrenia: study using the Brief Implicit Association
      Test.
AB  - BACKGROUND: If delusions serve as a defense mechanism in schizophrenia patients
      with paranoia, then they should show normal or high explicit self-esteem and low
      implicit self-esteem. However, the results of previous studies are inconsistent.
      One possible explanation for this inconsistency is that there are two types of
      paranoia, "bad me" (self-blaming) paranoia and "poor me" (non-self-blaming)
      paranoia. We thus examined implicit and explicit self-esteem and self-blaming
      tendency in patients with schizophrenia and schizoaffective disorder. We
      hypothesized that patients with paranoia would show lower implicit self-esteem
      and only those with non-self-blaming paranoia would experience a discrepancy
      between explicit and implicit self-esteem. METHODS: Participants consisted of
      patients with schizophrenia and schizoaffective disorder recruited from a day
      hospital (N=71). Participants were assessed for psychotic symptoms, using the
      Brief Psychiatric Rating Scale (BPRS), and self-blaming tendency, using the brief
      COPE. We also assessed explicit self-esteem, using the Rosenberg Self-Esteem
      Scale (RSES), implicit self-esteem, using Brief Implicit Association Test (BIAT),
      and discrepancy between explicit and implicit self-esteem. RESULTS: Contrary to
      our hypothesis, implicit self-esteem in paranoia and nonparanoia showed no
      statistical difference. As expected, only patients with non-self-blaming paranoia
      experienced a discrepancy between explicit and implicit self-esteem; other groups
      showed no such discrepancy. CONCLUSION: These results suggest that persecutory
      delusion plays a defensive role in non-self-blaming paranoia.

PMID- 25565845
TI  - Current investigations into the genotoxicity of zinc oxide and silica
      nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic
      potential, relevant mechanisms and biomarkers, artifacts, and limitations.
AB  - Engineered nanoparticles (NPs) are widely used in many sectors, such as food,
      medicine, military, and sport, but their unique characteristics may cause
      deleterious health effects. Close attention is being paid to metal NP
      genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying
      mechanisms remain to be elucidated. In this review, we address some metal and
      metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo.
      Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand
      breaks, oxidative DNA damage, and mutations. We also discuss several parameters
      that may affect genotoxic response, including physicochemical properties, widely
      used assays/end point tests, and experimental conditions. Although potential
      biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent
      findings in the literature render results inconclusive due to a variety of
      factors. Advantages and limitations related to different methods for
      investigating genotoxicity are described, and future directions and
      recommendations for better understanding genotoxic potential are addressed. 

PMID- 25565850
TI  - Prevalence of metabolic syndrome according to the presence of negative symptoms
      in patients with schizophrenia.
AB  - BACKGROUND: Metabolic syndrome (MetS) is one of the primary reasons for increased
      mortality in patients with schizophrenia. The mechanisms involved in its
      pathogenesis are not well understood. OBJECTIVE: To estimate the prevalence of
      MetS in adult outpatients with schizophrenia according to the presence or absence
      of negative symptoms. MATERIALS AND METHODS: A retrospective cohort study using
      electronic medical records was conducted. The Positive and Negative Syndrome
      Scale negative-symptom factor (N1-N4, N6, G7, and G16) was used as a framework
      for characterizing negative symptoms. MetS was defined using the National
      Cholesterol Education Program Adult Treatment Panel III diagnostic criteria. An
      analysis of covariance model was used for correction, with significance at
      P<0.05. RESULTS: One or more negative symptoms were present in 52.5% of a sample
      of 1,120 patients (mean age 46.8 years, men 58.4%). Dyslipidemia (48.7%),
      hypertension (38.2%), and diabetes mellitus (19.3%) were the most frequent
      comorbidities. The overall prevalence of MetS was 38.6% (95% confidence interval
      35.7%-41.5%), and was significantly higher in those patients with negative
      symptoms (43.9% versus 34.9%, P=0.002). MetS was significantly associated with
      the presence of negative symptoms, age, and physical comorbidity (odds ratios
      1.6, 1.2, and 1.2, respectively; P<0.05). CONCLUSION: A sedentary lifestyle and
      lack of physical exercise due to negative symptomatology may contribute to MetS
      development. Further studies are necessary to confirm this association and the
      underlying pathophysiological mechanisms.

PMID- 25565851
TI  - Prescriber utilization of dalfampridine extended release tablets in multiple
      sclerosis: a retrospective pharmacy and medical claims analysis.
AB  - PURPOSE: This study aimed to characterize the prescribing of dalfampridine
      extended release (D-ER) 10 mg tablet treatment in people with multiple sclerosis
      (MS). METHODS: A retrospective cohort study was performed using Medco pharmacy
      and medical claims. Medical claims were used to identify MS patients with more
      than one prescription for D-ER with 1 year of prior continuous enrollment
      (n=704). These patients were matched 2:1 on age, sex, and health insurance source
      with a comparison group of MS patients who were treatment naive for D-ER
      (n=1,403). Categorical data were analyzed by chi (2) test; ordinal data by
      Wilcoxon rank sum test; and continuous data by Student's t-test. RESULTS: Most
      patients were women aged 45-64 years. In the year preceding D-ER initiation, the
      prevalence of seizure and renal impairment was numerically lower in the D-ER
      cohort relative to those who were D-ER naive (seizure: 3.1% versus 4.7%,
      respectively; renal impairment: 4.3% versus 5.1%, respectively); however,
      prescriptions for antiepileptic drugs in the two cohorts were comparable. In the
      year preceding treatment initiation, 62% of the D-ER cohort was prescribed MS
      specific disease-modifying therapies relative to 45% who were D-ER naive.
      CONCLUSION: Seizure and renal impairment rates among D-ER-naive patients were
      consistent with published literature, yet rates among those prescribed D-ER
      during the year preceding treatment initiation were slightly lower than rates
      among D-ER-naive patients. Given that D-ER is contraindicated in patients with
      history of seizure or moderate or severe renal impairment, lower rates may
      indicate that risk-minimization strategies contributed to the lower prevalence.

PMID- 25565853
TI  - Bayesian imperfect information analysis for clinical recurrent data.
AB  - In medical research, clinical practice must often be undertaken with imperfect
      information from limited resources. This study applied Bayesian imperfect
      information-value analysis to realistic situations to produce likelihood
      functions and posterior distributions, to a clinical decision-making problem for
      recurrent events. In this study, three kinds of failure models are considered,
      and our methods illustrated with an analysis of imperfect information from a
      trial of immunotherapy in the treatment of chronic granulomatous disease. In
      addition, we present evidence toward a better understanding of the differing
      behaviors along with concomitant variables. Based on the results of simulations,
      the imperfect information value of the concomitant variables was evaluated and
      different realistic situations were compared to see which could yield more
      accurate results for medical decision-making. 

PMID- 25565852
TI  - Patient risk factors for developing a drug-related problem in a cardiology ward.
AB  - BACKGROUND: Because of the high incidence of drug-related problems (DRPs) among
      hospitalized patients with cardiovascular diseases and their potential impact on
      morbidity and mortality, it is important to identify the most susceptible
      patients, who therefore require closer monitoring of drug therapy. PURPOSE: To
      identify the profile of patients at higher risk of developing at least one DRP
      during hospitalization in a cardiology ward. METHOD: We consecutively included
      all patients hospitalized in the cardiology ward of a teaching hospital in 2009.
      DRPs were identified through a computerized warning system designed by the
      pharmacy department and integrated into the electronic medical record. RESULTS: A
      total of 964 admissions were included, and at least one DRP was detected in
      29.8%. The variables associated with a higher risk of these events were
      polypharmacy (odds ratio [OR]=1.228; 95% confidence interval [CI]=1.153-1.308),
      female sex (OR=1.496; 95% CI=1.026-2.180), and first admission (OR=1.494; 95%
      CI=1.005-2.221). CONCLUSION: Monitoring patients through a computerized warning
      system allowed the detection of at least one DRP in one-third of the patients.
      Knowledge of the risk factors for developing these problems in patients admitted
      to hospital for cardiovascular problems helps in identifying the most susceptible
      patients.

PMID- 25565854
TI  - Effectiveness and safety of Humalog Mix 50/50 versus Humalog Mix 75/25 in Chinese
      patients with type 2 diabetes.
AB  - Humalog Mix 75/25 insulin analog is widely used in the People's Republic of China
      to treat type 2 diabetes mellitus, but the Humalog Mix 50/50 analog is not as yet
      widely used or assessed. The purpose of this 12-week, parallel-group, randomized,
      treat-to-target study was to evaluate the difference in clinical efficacy,
      safety, and outcome of treatment between Humalog Mix 50/50 and Humalog Mix 75/25
      analogs in Chinese patients with type 2 diabetes mellitus. In total, 146 insulin
      naive patients with type 2 diabetes mellitus and aged 18-75 years were randomized
      and treated twice a day with either Humalog Mix 50/50 (group A) or Humalog Mix
      75/25 (group B). We monitored levels of fasting blood glucose, 2-hour
      postprandial blood glucose, and glycosylated hemoglobin (HbA1c) in patients in
      both groups prior to and 3 months post treatment, the average time to achieve
      target blood glucose level, and frequency of hypoglycemic episodes during
      treatment. We found that group A showed better glycemic control as per fasting
      blood glucose and 2-hour postprandial blood glucose than group B. Moreover, HbA1c
      levels in group A (5.5%+/-1.4%) were lower by 1.0%+/-0.1% (P<0.05) compared with
      those in group B (6.5%+/-1.5%). The time to achieve glucose control was shorter
      (P<0.05) in group A (12.6+/-3.6 days) than in group B (22.3+/-4.7 days).
      Regarding safety, no significant adverse events or severe hypoglycemia on
      treatment was observed in either group. Additionally, the 1:1 ratio of Humalog
      Mix 50/50 showed a trend towards fewer episodes of nocturnal hypoglycemia. Thus,
      compared with Humalog Mix 75/25, the high-proportion premix insulin analog,
      Humalog Mix 50/50 showed better glycemic control, achieved target blood glucose
      levels more rapidly and without an increase in hypoglycemic episodes in Chinese
      type 2 diabetic individuals and is recommended for use in clinical practice. 

PMID- 25565855
TI  - The effect of nonsurgical periodontal treatment on serum and saliva
      chitotriosidase activities in patients with periodontitis and coronary artery
      disease.
AB  - BACKGROUND: Plasma chitotriosidase activity, which is a marker of macrophage
      activation, has been reported to increase in inflammatory conditions and
      atherosclerosis. Chronic periodontitis has likely an important role in the
      development of coronary artery disease. In this study, we aimed to analyze the
      effect of chronic periodontitis on salivary and plasma chitotriosidase activities
      in patients with or without coronary atherosclerosis. METHODS: Fifty subjects
      were divided into four groups as controls (n=13), periodontitis (n=11), coronary
      artery disease (n=13), and periodontitis + coronary artery disease (n=13). Plasma
      and saliva chitotriosidase activities were measured by a fluorimetric method in
      all groups before the nonsurgical treatment of periodontitis and 5 weeks
      posttreatment in periodontitis groups. RESULTS: Salivary chitotriosidase activity
      was decreased after nonsurgical periodontal treatment in patients having
      periodontitis with or without coronary atherosclerosis. However, plasma
      activities remained unchanged. CONCLUSION: Although this study has some
      limitations like small sample size and short study duration, it can suggest that
      salivary chitotriosidase can have the potential to be used as a very useful and
      practical marker to evaluate the success of the periodontal treatment and/or host
      response. KEY FINDING: Salivary chitotriosidase can be used as a marker for the
      evaluation of the success of the periodontal treatment and/or host response.

PMID- 25565856
TI  - Rhegmatogenous retinal detachment due to a macular hole in a patient with pars
      planitis: a case report.
AB  - We report a rare case of rhegmatogenous retinal detachment due to a full
      thickness macular hole in a young patient with pars planitis. This study was an
      interventional case report. A 38-year-old Asian man presented with acute
      reduction of vision in his left eye. His past ocular history revealed a precedent
      of two intravitreal steroid injections in his left eye, and fundoscopy revealed a
      total bullous retinal detachment along with 360 degrees  snowbanking at the pars
      plana. Precise preoperative visualization of the posterior pole was impossible
      due to a dense nuclear cataract. During surgery, an unexpected full-thickness
      macular hole with no associated epiretinal membrane was observed, which resulted
      in the retinal detachment. This case of chronic pars planitis complicated with a
      full-thickness macular hole resulting in retinal detachment was successfully
      treated with vitrectomy, internal limiting membrane peeling, and perfluoropropane
      tamponade. Visual acuity improved from hand movements to 6/36 Snellen at 12
      months postsurgery. This case report illustrates the rare but possible
      association between pars planitis with macular hole formation and subsequent
      retinal detachment, underlying the beneficiary outcome of vitrectomy surgery both
      diagnostically and therapeutically. 

PMID- 25565857
TI  - Safety and effectiveness of a fixed-dose combination of olmesartan, amlodipine,
      and hydrochlorothiazide in clinical practice.
AB  - BACKGROUND: Clinical trials indicate that the use of fixed-dose combinations
      (FDCs) is associated with a higher level of treatment adherence and prolonged
      blood pressure (BP) control. The aim of this study was to document the safety and
      effectiveness of the FDC olmesartan/amlodipine/hydrochlorothiazide in patients
      with essential hypertension in clinical practice. METHODS: This multicenter,
      prospective, 24-week, noninterventional study enrolled 5,831 patients from
      primary care offices in Germany and Austria. Inclusion criteria were a diagnosis
      of essential hypertension and newly initiated treatment with the FDC. RESULTS:
      The mean age of patients was 63.5 years, almost 50% of patients had a time since
      diagnosis of essential hypertension of over 5 years, and approximately 70% of
      patients had at least one cardiovascular risk factor, including 29.4% of patients
      with diabetes mellitus. Following approximately 24 weeks of treatment, the mean
      reduction in systolic/diastolic BP was 29.0/14.0 mmHg, a BP response was observed
      by 94.2% of patients, and a target BP of <140/90 mmHg was attained in 67.5% of
      patients. At least one adverse drug reaction (ADR) was experienced by 1.2% of
      patients, with the most common being peripheral edema. Subanalyses demonstrated
      that the following factors did not have a significant influence on the ADR rate:
      age (<65 years versus >=65 years), diabetes mellitus (no/yes), cardiovascular
      risk (low/high), and concomitant medication (no/yes). CONCLUSION: This study
      demonstrates that in clinical practice, treatment with the three-drug combination
      as an FDC tablet resulted in a very high proportion of patients with a BP
      response and control, accompanied by a very low rate of ADRs.

PMID- 25565858
TI  - Overview of saxagliptin efficacy and safety in patients with type 2 diabetes and
      cardiovascular disease or risk factors for cardiovascular disease.
AB  - Most individuals with type 2 diabetes mellitus have or will develop multiple
      independent risk factors for cardiovascular disease, particularly coronary artery
      disease (CAD). CAD is the leading cause of morbidity and mortality among
      individuals with type 2 diabetes mellitus, and treating these patients is
      challenging. The risk of hypoglycemia, weight gain, or fluid retention with some
      diabetes medications should be considered when developing a treatment plan for
      individuals with a history of CAD or at risk for CAD. Dipeptidyl peptidase-4
      inhibitors are oral antihyperglycemic agents that inhibit the breakdown of the
      incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic
      polypeptide, resulting in increased glucose-dependent insulin secretion and
      suppression of glucagon secretion. Saxagliptin is a potent and selective
      dipeptidyl peptidase-4 inhibitor that improves glycemic control and is generally
      well tolerated when used as monotherapy and as add-on therapy to other
      antihyperglycemic medications. This review summarizes findings from recently
      published post hoc analyses of saxagliptin clinical trials that have been
      conducted in patients with and without a history of cardiovascular disease and in
      patients with and without various risk factors for cardiovascular disease. The
      results show that saxagliptin was generally well tolerated and consistently
      improved glycemic control, as assessed by reductions from baseline in glycated
      hemoglobin, fasting plasma glucose concentration, and postprandial glucose
      concentration, regardless of the presence or absence of baseline cardiovascular
      disease, hypertension, statin use, number of cardiovascular risk factors, or high
      Framingham 10-year cardiovascular risk score. 

PMID- 25565859
TI  - Indirect and direct costs of acute coronary syndromes with comorbid atrial
      fibrillation, heart failure, or both.
AB  - BACKGROUND: The objective of this study was to determine the direct and indirect
      costs of acute coronary syndromes (ACS) alone and with common cardiovascular
      comorbidities. METHODS: A retrospective analysis was conducted using the Medical
      Expenditure Panel Survey from 1998 to 2009. Four mutually exclusive cohorts were
      evaluated: ACS only, ACS with atrial fibrillation (AF), ACS with heart failure
      (HF), and ACS with both conditions. Direct costs were calculated for all-cause
      and cardiovascular-related health care resource utilization. Indirect costs were
      determined from productivity losses from missed days of work. Regression analysis
      was developed for each outcome controlling for age, US census region, insurance
      coverage, sex, race, ethnicity, education attainment, family income, and
      comorbidity burden. A negative binomial regression model was used for health care
      utilization variables. A Tobit model was utilized for health care costs and
      productivity loss variables. RESULTS: Total health care costs were greatest for
      those with ACS and both AF and HF ($38,484+/-5,191) followed by ACS with HF
      ($32,871+/-2,853), ACS with AF ($25,192+/-2,253), and ACS only ($17,954+/-563).
      Compared with the ACS only cohort, the mean all-cause adjusted health care costs
      associated with ACS with AF, ACS with HF, and ACS with AF and HF were $5,073 (95%
      confidence interval [CI] 719-9,427), $11,297 (95% CI 5,610-16,985), and $15,761
      (95% CI 4,784-26,738) higher, respectively. Average wage losses associated with
      ACS with and without AF and/or HF amounted to $5,266 (95% CI -7,765, -2,767),
      when compared with patients without these conditions. CONCLUSION: ACS imposes a
      significant economic burden at both the individual and society level,
      particularly when with comorbid AF and HF.

PMID- 25565860
TI  - Assessment and prognostic analysis of EGFR, HER2, and HER3 protein expression in
      surgically resected gastric adenocarcinomas.
AB  - AIM: To investigate the significance of epidermal growth factor receptor (EGFR),
      human epidermal growth factor receptor (HER)2, and HER3 expression on survival
      outcomes in Chinese gastric cancer patients. MATERIALS AND METHODS: Formalin
      fixed, paraffin-embedded specimens from 121 patients who underwent gastrectomy at
      Shanghai Renji Hospital from 2007-2010 were retrospectively examined.
      Fluorescence in situ hybridization and immunohistochemistry techniques were used
      to identify gene amplification and protein overexpression. Correlations between
      the expression or amplification of HER family genes and clinicopathological
      parameters were then determined using statistical analysis. RESULTS: EGFR protein
      overexpression, an increase in HER2 copy number and gene amplification, and HER3
      protein overexpression were identified in 33.1%, 17.4%, and 62.0% of samples,
      respectively. Statistical analysis showed a significant association between EGFR
      expression and tumor invasion depth or tumor stage. HER2 was also shown to be
      significantly associated with the tumor grade. In addition, EGFR protein
      overexpression was found to be significantly associated with worse overall
      survival (P=0.03). CONCLUSION: The HER family members showed a high expression in
      gastric cancer. EGFR protein expression was associated with overall survival.

PMID- 25565861
TI  - Neoadjuvant hormone therapy following treatment with robotic-assisted radical
      prostatectomy achieved favorable in high-risk prostate cancer.
AB  - PURPOSE: Patients with a high risk of prostate carcinoma typically have higher
      rates of positive surgical margins and biochemical failure following radical
      prostatectomy and adjuvant hormone therapy. In this study, we assessed the
      effects of neoadjuvant hormone therapy (NHT) on prostate carcinoma in high-risk
      patients following robotic-assisted radical prostatectomy (RARP). METHODS: This
      retrospective study investigated the medical records of 28 patients who underwent
      RARP between January 2009 and October 2013. Twenty-two patients underwent NHT
      prior to RARP. Furthermore, six patients did not undergo NHT prior to RARP.
      Parameters including age, operating time, blood loss, blood transfusion status,
      and cancer stage were checked against anatomical correlations. Potential
      predictors of prolonged operating time and prolonged surgical procedures were
      assessed using multiple logistic regressions. RESULTS: NHT was shown to be an
      independent predictor of prolonged total operating time. Tumor stage alterations
      did not appear to be associated with NHT followed by RARP. The patients who
      underwent NHT were not more likely to have positive surgical margins, and an
      increase in patients requiring blood transfusion was not seen. CONCLUSION: NHT
      appears to increase operative time during RARP. However, the perioperative
      morbidity of NHT patients undergoing RARP appears to be equivalent with that of
      non-NHT patients.

PMID- 25565862
TI  - Lumbosacral plexus delineation, dose distribution, and its correlation with
      radiation-induced lumbosacral plexopathy in cervical cancer patients.
AB  - BACKGROUND: To evaluate the dose distribution to the lumbosacral plexus (LSP) and
      its correlation with radiation-induced lumbosacral plexopathy (RILSP) in patients
      with cervical cancer treated with intensity-modulated radiotherapy (IMRT) and
      high-dose-rate brachytherapy. MATERIALS AND METHODS: After meeting eligibility
      criteria, 50 patients with cervical cancer were selected who were treated with
      IMRT and high-dose-rate brachytherapy, and the LSP was contoured. Mean volume;
      percentages of LSP volume absorbing 40, 50, 55, and 60 Gy (V30, V40, V50, V55,
      and V60) and point doses (P1, P2, P3, P4, P5, P6, P7, P8, P9, and P10); and RILSP
      incidence were calculated. RESULTS: At 60 months of follow-up, four patients (8%)
      were found to have grade 2/3 RILSP. The mean maximal LSP dose in patients with
      RILSP was 59.6 Gy compared with 53.9 Gy in patients without RILSP (control;
      P=0.04). The mean values of V40, V50, V55, and V60 in patients with RILSP versus
      control were 61.8% versus 52.8%, 44.4% versus 27.7%, 8.0% versus 0.3% and 1.8%
      versus 0%, respectively (P=0.01, 0.001, 0.001, and 0.001, respectively).
      CONCLUSION: The delineation of the LSP during IMRT planning may reduce the risk
      for RILSP. The mean values of V40, V50, V55, and V60 for LSP should be less than
      55%, 30%, 5%, and 0.5%, respectively; however, further studies are warranted.

PMID- 25565863
TI  - Fertility sparing surgery in young women affected by endometrial stromal sarcoma:
      an oncologic dilemma or a reliable option? review of literature starting from a
      peculiar case.
AB  - BACKGROUND: Endometrial stromal sarcoma (ESS) is a term used to define a rare
      neoplasm that accounts for approximately 0.2%-1% of all uterine malignancies; it
      is, however, implicated in an estimated 10%-15% of those malignancies with a
      mesenchymal component. Recent evidence suggests that while the preservation of
      the ovaries may be considered appropriate in premenopausal women, hysterectomy
      and bilateral salpingo-oophorectomy remains the recommended treatment in
      postmenopausal women. Currently, only a few case series reporting the treatment
      of ESS in young women with a desire to preserve fertility and thus subjected to a
      fertility-sparing surgery are available in the literature. CASE PRESENTATION: We
      report a peculiar case of early stage ESS treated by laparoscopic fertility
      sparing surgery and a strict follow-up program (every 3 months) of imaging and
      clinical evaluation. The patient remained disease free 1 year after primary
      treatment. Three months after completing oncological follow-up, the patient
      conceived spontaneously and is, to date, pregnant at 11 weeks of gestation
      without evidence of recurrent disease or obstetric complications. CONCLUSION:
      Based on our case report and in accordance with the data available, we suggest
      that in young patients affected by early stage ESS who wish to preserve
      reproductive function, fertility-sparing surgery could represent a valid option,
      though strict oncological follow-up remains mandatory.

PMID- 25565864
TI  - Disruption of human papillomavirus 16 E6 gene by clustered regularly interspaced
      short palindromic repeat/Cas system in human cervical cancer cells.
AB  - High-risk human papillomavirus (HPV), especially HPV16, is considered a main
      causative agent of cervical cancer. Upon HPV infection, the viral oncoprotein E6
      disrupts the host tumor-suppressor protein p53, thus promoting malignant
      transformation of normal cervical cells. Here, we used the newly developed
      programmable ribonucleic acid-guided clustered regularly interspaced short
      palindromic repeat (CRISPR)/Cas system to disrupt the HPV16 E6 gene. We showed
      that HPV16 E6 deoxyribonucleic acid was cleaved at specific sites, leading to
      apoptosis and growth inhibition of HPV16-positive SiHa and CaSki cells, but not
      HPV-negative C33A or human embryonic kidney 293 cells. We also observed
      downregulation of the E6 protein and restoration of the p53 protein. These data
      proved that the HPV16 E6 ribonucleic acid-guided CRISPR/Cas system might be an
      effective therapeutic agent in treating HPV infection-related cervical
      malignancy. 

PMID- 25565865
TI  - Using an innovative multiple regression procedure in a cancer population (Part
      1): detecting and probing relationships of common interacting symptoms (pain,
      fatigue/weakness, sleep problems) as a strategy to discover influential symptom
      pairs and clusters.
AB  - BACKGROUND: The majority of patients with advanced cancer experience symptom
      pairs or clusters among pain, fatigue, and insomnia. Improved methods are needed
      to detect and interpret interactions among symptoms or diesease markers to reveal
      influential pairs or clusters. In prior work, I developed and validated
      sequential residual centering (SRC), a method that improves the sensitivity of
      multiple regression to detect interactions among predictors, by conditioning for
      multicollinearity (shared variation) among interactions and component predictors.
      MATERIALS AND METHODS: Using a hypothetical three-way interaction among pain,
      fatigue, and sleep to predict depressive affect, I derive and explain SRC
      multiple regression. Subsequently, I estimate raw and SRC multiple regressions
      using real data for these symptoms from 268 palliative radiation outpatients.
      RESULTS: Unlike raw regression, SRC reveals that the three-way interaction (pain
      * fatigue/weakness * sleep problems) is statistically significant. In follow-up
      analyses, the relationship between pain and depressive affect is aggravated
      (magnified) within two partial ranges: 1) complete-to-some control over
      fatigue/weakness when there is complete control over sleep problems (ie, a subset
      of the pain-fatigue/weakness symptom pair), and 2) no control over
      fatigue/weakness when there is some-to-no control over sleep problems (ie, a
      subset of the pain-fatigue/weakness-sleep problems symptom cluster). Otherwise,
      the relationship weakens (buffering) as control over fatigue/weakness or sleep
      problems diminishes. CONCLUSION: By reducing the standard error, SRC unmasks a
      three-way interaction comprising a symptom pair and cluster. Low-to-moderate
      levels of the moderator variable for fatigue/weakness magnify the relationship
      between pain and depressive affect. However, when the comoderator variable for
      sleep problems accompanies fatigue/weakness, only frequent or unrelenting levels
      of both symptoms magnify the relationship. These findings suggest that a
      countervailing mechanism involving depressive affect could account for the
      effectiveness of a cognitive behavioral intervention to reduce the severity of a
      pain, fatigue, and sleep disturbance cluster in a previous randomized trial.

PMID- 25565866
TI  - Using an innovative multiple regression procedure in a cancer population (Part
      II): fever, depressive affect, and mobility problems clarify an influential
      symptom pair (pain-fatigue/weakness) and cluster (pain-fatigue/weakness-sleep
      problems).
AB  - BACKGROUND: Most patients with advanced cancer experience symptom pairs or
      clusters among pain, fatigue, and insomnia. However, only combinations where
      symptoms are mutually influential hold potential for identifying patient
      subgroups at greater risk, and in some contexts, interventions with "cross-over"
      (multisymptom) effects. Improved methods to detect and interpret interactions
      among symptoms, signs, or biomarkers are needed to reveal these influential pairs
      and clusters. I recently created sequential residual centering (SRC) to reduce
      multicollinearity in moderated regression, which enhances sensitivity to detect
      these interactions. METHODS: I applied SRC to moderated regressions of single
      item symptoms that interact to predict outcomes from 268 palliative radiation
      outpatients. I investigated: 1) the hypothesis that the interaction, pain *
      fatigue/weakness * sleep problems, predicts depressive affect only when fever
      presents, and 2) an exploratory analysis, when fever is absent, that the
      interaction, pain * fatigue/weakness * sleep problems * depressive affect,
      predicts mobility problems. In the fever context, three-way interactions (and
      derivative terms) of the four symptoms (pain, fatigue/weakness, fever, sleep
      problems) are tested individually and simultaneously; in the non-fever context, a
      single four-way interaction (and derivative terms) is tested. RESULTS: Fever
      interacts separately with fatigue/weakness and sleep problems; these comoderators
      each magnify the pain-depressive affect relationship along the upper or full
      range of pain values. In non-fever contexts, fatigue/weakness, sleep problems,
      and depressive affect comagnify the relationship between pain and mobility
      problems. CONCLUSION: Different mechanisms contribute to the pain *
      fatigue/weakness * sleep problems interaction, but all depend on the presence of
      fever, a sign/biomarker/symptom of proinflammatory sickness behavior. In non
      fever contexts, depressive affect is no longer an outcome representing malaise
      from the physical symptoms of sickness, but becomes a fourth symptom of the
      interaction. In outpatient subgroups at heightened risk, single interventions
      could potentially relieve multiple symptoms when fever accompanies sickness
      malaise and in non-fever contexts with mobility problems. SRC strengthens
      insights into symptom pairs/clusters.

PMID- 25565867
TI  - The landscape of alternative splicing in cervical squamous cell carcinoma.
AB  - BACKGROUND: Alternative splicing (AS) is a key regulatory mechanism in protein
      synthesis and proteome diversity. In this study, we identified alternative
      splicing events in four pairs of cervical squamous cell carcinoma (CSCC) and
      adjacent nontumor tissues using RNA sequencing. METHODS: The transcripts of the
      four paired samples were thoroughly analyzed by RNA sequencing. SpliceMap
      software was used to detect the splicing junctions. Kyoto Encyclopedia of Genes
      and Genomes pathway analysis was conducted to detect the alternative spliced
      genes-related signal pathways. The alternative spliced genes were validated by
      reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: There were 35
      common alternative spliced genes in the four CSCC samples; they were novel and
      CSCC specific. Sixteen pathways were significantly enriched (P<0.05). One novel
      5'AS site in the KLHDC7B gene, encoding kelch domain-containing 7B, and an exon
      skipping site in the SYCP2 gene, encoding synaptonemal complex 2, were validated
      by RT-PCR. The KLHDC7B gene with 5'AS was found in 67.5% (27/40) of CSCC samples
      and was significantly related with cellular differentiation and tumor size. The
      exon-skipping site of the SYCP2 gene was found in 35.0% (14/40) of CSCC samples
      and was significantly related with depth of cervical invasion. CONCLUSION: The
      KLHDC7B and the SYCP2 genes with alternative spliced events might be involved in
      the development and progression of CSCC and could be used as biomarkers in the
      diagnosis and prognosis of CSCC.

PMID- 25565868
TI  - Decreased expression of APAF-1 and increased expression of cathepsin B in
      invasive pituitary adenoma.
AB  - PURPOSE: Apoptotic protease-activating factor-1 (APAF-1) and cathepsin B are
      important functional proteins in apoptosis; the former is involved in the
      intrinsic (mitochondrial) pathway, while the latter is associated with both
      intrinsic and extrinsic pathways. Changes in the expression of apoptosome-related
      proteins could be useful indicators of tumor development since a priori defects
      in the mitochondrial pathway might facilitate the inception and progression of
      human neoplasms. Our aim was to evaluate the profiles of APAF-1 and cathepsin B
      in relation with other molecules involved in apoptosis/proliferation and to
      correlate them with the aggressive behavior of invasive pituitary adenomas.
      MATERIALS AND METHODS: APAF-1 and cathepsin B were assessed in tissue samples
      from 30 patients with pituitary adenomas, of which 16 were functional adenomas
      and 22 were invasive adenomas. RESULTS: A positive relationship between high
      proliferation and invasiveness was observed in invasive pituitary adenomas when
      compared to their noninvasive counterparts (Ki-67 labeling index - 4.72% versus
      1.75%). Decreased expression of APAF-1 was recorded in most of the invasive
      adenomas with a high proliferation index, while the cathepsin B level was
      elevated in this group. We have noticed a negative correlation between the low
      level of APAF-1 and invasiveness (63.63%; P<0.01); at the same time, a positive
      correlation between cathepsin B expression and invasiveness (59.09%; P<0.01) was
      found. In all, 81.25% out of the total APAF-1-positive samples were cathepsin B
      negative (P<0.01); 76.92% out of the total cathepsin B-positive samples were APAF
      1-negative (P<0.01). These results were reinforced by an apoptosis protein array
      examination, which showed inhibition of the extrinsic apoptotic pathway in an
      invasive pituitary adenoma. CONCLUSION: A bidirectional-inverted relationship
      between APAF-1 and cathepsin B expressions was noticed. One might hypothesize
      that shifting the balance between mediators of cell death could result in changes
      in tumor behavior.

PMID- 25565869
TI  - Breast metastases of gastric signet-ring cell carcinoma: a report of two cases
      and review of the literature.
AB  - It is occasionally difficult to diagnose breast metastasis of gastric carcinoma
      because of its rarity. However, to appropriately treat patients with breast
      tumors without delay, it is important to distinguish metastatic cancer from
      primary breast cancer. We report two cases of breast metastasis of gastric
      carcinoma and review the literature. The first case was a 41-year-old female
      diagnosed with bilateral pelvic tumors who visited the outpatient clinic because
      of pain and enlargement of both breasts. Ultrasonography showed diffuse
      hypoechoic lesions, which were enhanced on gadolinium-enhanced magnetic resonance
      imaging in the bilateral mammary gland. Core needle biopsy of the right breast
      revealed signet-ring cells, which were also identified in the resected bilateral
      pelvic tumors. Subsequent upper gastrointestinal endoscopy revealed signet-ring
      cell carcinoma in the stomach, and the bilateral breast lesions were diagnosed as
      metastases of gastric carcinoma. The second case was a 34-year-old female
      diagnosed with cervical metastasis of signet-ring cell carcinoma who was referred
      to the breast cancer clinic because of a nodule in the left breast detected by
      computed tomography. Ultrasonography showed a hypoechoic nodule that was enhanced
      on gadolinium-enhanced magnetic resonance imaging. Because the pathologic
      findings for the left breast nodule were quite similar to those of gastric cancer
      and its cervical metastasis, the breast nodule was diagnosed as a metastasis of
      gastric carcinoma. When a breast tumor is suspected to have metastasized from a
      primary tumor in another organ, particularly if signet-ring cells are found, the
      possibility that gastric cancer is present should be considered. 

PMID- 25565871
TI  - Cost-consequence analysis of long-term prophylaxis in the treatment of von
      Willebrand disease in the Italian context.
AB  - PURPOSE: Prophylaxis with von Willebrand factor (VWF)/factor VIII (FVIII)
      concentrates is a potential approach for patients with severe von Willebrand
      disease (VWD). As far as we are aware, to date there have been no
      pharmacoeconomic analyses in order to assess the economic impact of treatments
      for severe VWD. The analysis presented here estimates the cost-benefit ratio of
      VWF with a low FVIII content when compared with VWF/FVIII concentrates currently
      used in Italy for long-term prophylaxis in patients with severe VWD. METHODS: A
      cost-consequence analysis was undertaken to assess the economic impact of the
      treatment of severe VWD from the perspective both of the Italian National Health
      Service and society. The analysis was based on four case reports of long-term
      prophylaxis with VWD with VWF/FVIII concentrates and VWF with a low FVIII
      content. The costs per patient included direct and indirect costs for each
      treatment. RESULTS: Considering the four case reports, health care costs (without
      cost of treatment) and indirect costs per patient per year were lower with VWF
      with a low FVIII content than VWF/FVIII concentrates. The total health care costs
      (without cost of treatment) and indirect costs avoided with VWF with a low FVIII
      content per patient per year ranged from ?2,295 to ?17,530 and from ?1,867 to
      ?4,978, respectively. CONCLUSION: VWF with a low FVIII content seems to be a cost
      effective treatment option for patients with severe VWD. Although the drug cost
      per se is higher, the use of VWF with a low FVIII content is associated with
      decreased consumption of hospital resources and fewer lost working days due to
      bleedings and consequently with an improvement of the quality of life of the
      patients.

PMID- 25565870
TI  - Fetal exposure to a diabetic intrauterine environment resulted in a failure of
      cord blood endothelial progenitor cell adaptation against chronic hypoxia.
AB  - Gestational diabetes mellitus (GDM) has long-term health consequences, and fetal
      exposure to a diabetic intrauterine environment increases cardiovascular risk for
      her adult offspring. Some part of this could be related to their endothelial
      progenitor cells (EPCs). Understanding the vessel-forming ability of human
      umbilical cord blood (HUCB)-derived endothelial colony-forming cells (ECFCs)
      against pathological stress such as GDM response to hypoxia could generate new
      therapeutic strategies. This study aims to investigate the role of chronic
      hypoxia in EPCs functional and vessel-forming ability in GDM subjects. Each ECFC
      was expressed in endothelial and pro-angiogenic specific markers, namely
      endothelial nitric oxide synthase (eNOS), platelet (PECAM-1) endothelial cell
      adhesion molecule 1, vascular endothelial-cadherin CdH5 (Ca-dependent cell
      adhesion molecule), vascular endothelial growth factor A, (VEGFA) and insulin
      like growth factor 1 (IGF1). Chronic hypoxia did not affect CdH5, but PECAM1 MRNA
      expressions were increased in control and GDM subjects. Control hypoxic and GDM
      normoxic VEGFA MRNA expressions and hypoxia-inducible factor 1-alpha (HIF1alpha)
      protein expressions were significantly increased in HUCB ECFCs. GDM resulted in
      most failure of HUCB ECFC adaptation and eNOS protein expressions against chronic
      hypoxia. Chronic hypoxia resulted in an overall decline in HUCB ECFCs'
      proliferative ability due to reduction of clonogenic capacity and diminished
      vessel formation. Furthermore, GDM also resulted in most failure of cord blood
      ECFC adaptation against chronic hypoxic environment. 

PMID- 25565872
TI  - Cost of HAART in Italy: multicentric evaluation and determinants from a large HIV
      outpatient cohort.
AB  - BACKGROUND: As HIV infection turned into a chronic treatable disease, now ranking
      as one of the most costly in medicine, long-term sustainability of highly active
      antiretroviral treatment (HAART) expenses became a major issue, especially in
      countries with universal access to care. Identification of determinants of higher
      HAART costs may therefore help in controlling costs of care, while keeping high
      levels of retention in care and viral suppression. METHODS: With this aim, we
      enrolled a large multicentric sample of consecutive unselected human
      immunodeficiency virus (HIV) patients followed at five sites of care in Italy,
      and evaluated annual individual HAART costs in relation to a number of
      sociodemographic, clinical, and laboratory variables. RESULTS: We enrolled 2,044
      patients, including 1,902 on HAART. Mean HAART costs were ?9,377+/-?3,501 (range
      782-29,852) per year, with remarkable site-based differences, possibly related to
      the different composition of local assisted populations. Percentages of patients
      on viral suppression were homogeneously high across all study sites. The factors
      identified by cross-validation were line of HAART, diagnosis of acquired immune
      deficiency syndrome, current CD4 T-cell count, and detectable HIV viremia >50
      copies/mL. In the final multivariable model, HAART costs were independently
      directly associated with more advanced HAART line (P<0.001) and inversely
      correlated with current CD4 T-cell count (P=0.024). Site of care held independent
      prediction of higher costs, with marked control of expenses at sites 2 (P=0.001)
      and 5 (P<0.001). CONCLUSION: Higher costs of HAART were strongly associated with
      previous treatment failures, detectable HIV viremia, and lower CD4 T-cell count
      at the time of evaluation, with no correlation at all with sex, age, hepatitis C
      virus coinfection, and nadir CD4 T-cell counts. Newer drugs, which are typically
      those associated with high prices, at the time of the analysis were still
      prevalently prescribed to rescue and maintain viral suppression in patients with
      more complex treatment history. Further analyses of the contribution of the
      single drug/regimen to the estimated cost are warranted.

PMID- 25565873
TI  - Health outcomes in diabetics measured with Minnesota Community Measurement
      quality metrics.
AB  - OBJECTIVE: Our objective was to understand the relationship between optimal
      diabetes control, as defined by Minnesota Community Measurement (MCM), and
      adverse health outcomes including emergency department (ED) visits,
      hospitalizations, 30-day rehospitalization, intensive care unit (ICU) stay, and
      mortality. PATIENTS AND METHODS: In 2009, we conducted a retrospective cohort
      study of empaneled Employee and Community Health patients with diabetes mellitus.
      We followed patients from 1 September 2009 until 30 June 2011 for hospitalization
      and until 5 January 2014 for mortality. Optimal control of diabetes mellitus was
      defined as achieving the following three measures: low-density lipoprotein (LDL)
      cholesterol <100 mg/mL, blood pressure <140/90 mmHg, and hemoglobin A1c <8%.
      Using the electronic medical record, we assessed hospitalizations, ED visits, ICU
      stays, 30-day rehospitalizations, and mortality. The chi-square or Wilcoxon rank
      sum tests were used to compare those with and without optimal control. We used
      Cox proportional hazard models to estimate the associations between optimal
      diabetes mellitus status and each outcome. RESULTS: We identified 5,731 empaneled
      patients with diabetes mellitus; 2,842 (49.6%) were in the optimal control
      category. After adjustment, we observed that non-optimally controlled patients
      had higher risks for hospitalization (hazard ratio [HR] 1.11; 95% confidence
      interval [CI] 1.00-1.23), ED visits (HR 1.15; 95% CI 1.06-1.25), and mortality
      (HR 1.29; 95% CI 1.09-1.53) than diabetic patients with optimal control. No
      differences were observed in ICU stay or 30-day rehospitalization. CONCLUSION:
      Diabetic patients without optimal control had higher risks of adverse health
      outcomes than those with optimal control. Patients with optimal control defined
      by the MCM were associated with decreased morbidity and mortality.

PMID- 25565875
TI  - Assessment of local skin reactions with a sequential regimen of cryosurgery
      followed by ingenol mebutate gel, 0.015%, in patients with actinic keratosis.
AB  - Lesion-directed and field-directed therapies are used to treat actinic keratosis
      (AK). Therapeutic approaches that combine both types of therapies may improve the
      successful elimination of AKs. A randomized, double-blind, vehicle-controlled
      study evaluated the safety, tolerability, and efficacy of topical field treatment
      with ingenol mebutate gel, 0.015%, after cryosurgery to AKs on the face and
      scalp. Patients with 4-8 visible discrete AKs in a 25-cm(2) contiguous area
      received cryosurgery of all AKs at baseline. After a 3-week healing period,
      patients applied ingenol mebutate gel, 0.015%, or vehicle gel once daily for 3
      consecutive days to the treatment area. The incidence, severity, and time course
      of the development and resolution of local skin reactions were measured from
      baseline to week 11. Local skin reactions peaked shortly after completion of
      ingenol mebutate treatment and generally resolved within 2 weeks. The mean (95%
      confidence interval) composite score (maximum range, 0-24) for these reactions
      was higher in patients with treatment of AKs on the face, 9.3 (8.5-10.1), as
      compared with the scalp, 5.8 (4.3-7.4). Erythema and flaking/scaling were the
      major contributors to the composite local skin reaction score. These results show
      that local skin reactions associated with ingenol mebutate treatment of the face
      or scalp are well tolerated after recent cryosurgery. 

PMID- 25565874
TI  - Salivary glucose concentration exhibits threshold kinetics in normal-weight,
      overweight, and obese children.
AB  - BACKGROUND: Metabolic syndrome in childhood predicts the development of
      cardiovascular disease and type 2 diabetes (T2D) in adulthood. Testing for
      features of metabolic syndrome, such as fasting plasma glucose concentration,
      requires blood sampling which can be difficult in children. Here we evaluated
      salivary glucose concentration as a surrogate measurement for plasma glucose
      concentration in 11-year-old US children. METHODS: Children from Portland, Maine,
      and Cambridge, Massachusetts, with a mean age of 10.6+/-0.2 years provided 6-hour
      fasting samples of both blood and whole saliva. Salivary glucose levels were
      measured with a high-sensitivity assay (sensitivity =0.002 mg/dL). Plasma glucose
      levels were determined by a commercial clinical laboratory. Blood pressure,
      salivary flow rate, height, and weight were also measured. RESULTS: Of the 65
      children enrolled, there were two underweight children (3.1%), 30 normal-weight
      children (46.2%), 12 overweight children (18.4%), and 21 obese children (32.3%).
      The mean overall glucose concentrations were 0.11+/-0.02 mg/dL in saliva and
      86.3+/-0.8 mg/dL in plasma, and these did not differ significantly by body-weight
      groups. By regression analysis, the plasma concentration equaled 13.5 times the
      saliva concentration, with a threshold level of 84.8 mg/dL. Salivary glucose
      values less than threshold plasma concentration were essentially zero. Diagnostic
      analysis indicated a positive predictive value of 50%, a negative predictive
      value of 90%, and a sensitivity and specificity both of approximately 75%. The
      salivary glucose concentration did not vary with saliva flow rate. CONCLUSION:
      Taking into account the threshold response characteristics of the salivary
      glucose concentration response, these results suggest that testing salivary
      glucose levels may be useful as a screening assay for high fasting plasma glucose
      levels. The low false positive value is important to assure a low fraction of
      missed diagnoses.

PMID- 25565877
TI  - Cathelicidin suppresses colon cancer development by inhibition of cancer
      associated fibroblasts.
AB  - BACKGROUND: Cathelicidin (LL-37 in humans and mCRAMP in mice) represents a family
      of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated
      fibroblasts can promote the proliferation of colon cancer cells and growth of
      colon cancer tumors. METHODS: We examined the role of cathelicidin in the
      development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell
      derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated
      colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral
      mechanism of cathelicidin via the inhibition of epithelial-mesenchymal transition
      (EMT) of colon cancer cells and fibroblast-supported colon cancer cell
      proliferation. RESULTS: Intravenous administration of cathelicidin expressing
      adeno-associated virus significantly reduced the size of tumors, tumor-derived
      collagen expression, and tumor-derived fibroblast expression in HT-29-derived
      subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin
      peptide significantly reduced the size and number of colonic tumors in
      azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in
      tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the
      collagen expression and vimentin-positive fibroblast expression in colonic
      tumors. Cathelicidin did not directly affect HT-29 cell viability, but did
      significantly reduce tumor growth factor-beta1-induced EMT of colon cancer cells.
      Media conditioned by the human colonic CCD-18Co fibroblasts promoted human colon
      cancer HT-29 cell proliferation. Cathelicidin pretreatment inhibited colon cancer
      cell proliferation mediated by media conditioned by human colonic CCD-18Co
      fibroblasts. Cathelicidin disrupted tubulin distribution in colonic fibroblasts.
      Disruption of tubulin in fibroblasts reduced fibroblast-supported colon cancer
      cell proliferation. CONCLUSION: Cathelicidin effectively inhibits colon cancer
      development by interfering with EMT and fibroblast-supported colon cancer cell
      proliferation.

PMID- 25565876
TI  - Endoscopic therapy in chronic pancreatitis: current perspectives.
AB  - Endoscopic therapy in chronic pancreatitis (CP) aims to provide pain relief and
      to treat local complications, by using the decompression of the pancreatic duct
      and the drainage of pseudocysts and biliary strictures, respectively. This is the
      reason for using it as first-line therapy for painful uncomplicated CP. The
      clinical response has to be evaluated at 6-8 weeks, when surgery may be chosen.
      This article reviews the main possibilities of endoscopic retrograde
      cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) therapies.
      Endotherapy for pancreatic ductal stones uses ultrasound wave lithotripsy and
      sometimes additional stone extractions. The treatment of pancreatic duct
      strictures consists of a single large stenting for 1 year. If the stricture
      persists, simultaneous multiple stents are applied. In case of unsuccessful ERCP,
      the EUS-guided drainage of the main pancreatic duct (MPD) or a rendezvous
      technique can solve the ductal strictures. EUS-guided celiac plexus block has
      limited efficiency in CP. The drainage of symptomatic or complicated pancreatic
      pseudocysts can be performed transpapillarily or
      transgastrically/transduodenally, preferably by EUS guidance. When the biliary
      stricture is symptomatic or progressive, multiple plastic stents are indicated.
      In conclusion, as in many fields of symptomatic treatment, endoscopy remains the
      first choice, either by using ERCP or EUS-guided procedures, after consideration
      of a multidisciplinary team with endoscopists, surgeons, and radiologists.
      However, what is crucial is establishing the right timing for surgery. 

PMID- 25565879
TI  - Celiac disease in children: is it a problem in Kuwait?
AB  - BACKGROUND: Celiac disease (CD) is a chronic inflammatory disease of the small
      intestine triggered by gluten ingestion. The objective of this study is to
      describe our experience with CD children in Kuwait. METHODS: The records of
      children with CD seen in the pediatric gastroenterology unit between February
      1998 and December 2010 were retrospectively reviewed. Patients were referred
      because of symptoms or positive CD antibody screening of a high-risk group (type
      1 diabetes and Down syndrome). RESULTS: Forty-seven patients were diagnosed: 53%
      were symptomatic and 47% were identified by screening. The median age at
      diagnosis was 66 (range 7-189) months. All cases were biopsy-proven except one.
      The symptomatic patients were significantly younger than those identified
      following screening (P<0.004). In the whole group, 66% were females and 77% were
      Kuwaitis; 9% had a positive family history of CD. The estimated cumulative
      incidence was 6.9/10(5). The median duration of symptoms before diagnosis was 8.5
      (range 2-54) months. Failure to thrive was the most common presenting complaint
      (72%) followed by diarrhea (64%) and abdominal distension (56%). Atypical
      manifestations were seen in 60% of patients. Underweight and short stature were
      confirmed in 19% and 17% of patients, respectively. Overweight and obesity were
      detected in 14% and 6%, respectively. CD serology was based on a combination of
      antiendomysial and antigliadin antibodies. The median follow up was 24 (range 12
      144) months. All patients were commenced on a gluten free diet, but good
      compliance was only achieved in 78%. CONCLUSION: The low frequency of childhood
      CD in Kuwait could probably be attributed to either an underestimation of the
      atypical presentations or failure of proper screening. Also, adherence to a
      gluten free diet is a major problem in our population.

PMID- 25565878
TI  - Developments in flexible endoscopic surgery: a review.
AB  - Flexible endoscopy is increasingly developing into a therapeutic instead of a
      purely diagnostic discipline. Improved visualization makes early lesions easily
      detectable and allows us to decide ad hoc on the required treatment. Deep
      enteroscopy allows the exploration of even the small bowel - for long a "white
      spot" for gastrointestinal endoscopy - and to perform direct treatment.
      Endoscopic submucosal dissection is a considerable step forward in oncologically
      correct endoscopic treatment of (early) malignant lesions. Though still
      technically challenging, it is increasingly facilitated by new manipulation
      techniques and tools that are being steadily optimized. Closure of wall defects
      and hemostasis could be improved significantly. Even the anatomy beyond the
      gastrointestinal wall is being explored by the therapeutic use of endoluminal
      ultrasound. Endosonographic-guided surgery is not only a suitable fallback
      solution if conventional endoscopic retrograde cholangiopancreatography fails,
      but even makes necrosectomy procedures, abscess drainage, and neurolysis feasible
      for the endoscopist. Newly developed endoscopic approaches aim at formerly
      distinctive surgical domains like gastroesophageal reflux disease, appendicitis,
      and cholecystitis. Combined endoscopic/laparoscopic interventional techniques
      could become the harbingers of natural orifice transluminal endoscopic surgery,
      whereas pure natural orifice transluminal endoscopic surgery is currently still
      in its beginnings. 

PMID- 25565880
TI  - Evaluating targets and costs of treatment for secondary hyperparathyroidism in
      incident dialysis patients: the FARO-2 study.
AB  - BACKGROUND: The aim of this analysis was to estimate biochemical parameters and
      the costs of treatment of secondary hyperparathyroidism (SHPT) in a subpopulation
      of the FARO-2 study. METHODS: The FARO-2 observational study aimed at evaluating
      the patterns of treatment for SHPT in naive hemodialysis patients. Data related
      to pharmacological treatments and biochemical parameters (parathyroid hormone
      [PTH], calcium, phosphate) were recorded at entry to hemodialysis (baseline) and
      6 months later (second survey). The analysis was performed from the Italian
      National Health Service perspective. RESULTS: Two prominent treatment groups were
      identified, ie, one on oral calcitriol (n=105) and the other on intravenous
      paricalcitol (n=33); the intravenous calcitriol and intravenous paricalcitol +
      cinacalcet combination groups were not analyzed due to low patient numbers. At
      baseline, serum PTH levels were significantly higher in the intravenous
      paricalcitol group (P<0.0001). At the second survey, the intravenous paricalcitol
      group showed a higher percentage of patients at target for PTH than in the oral
      calcitriol group without changing the percentage of patients at target for
      phosphate. Moreover, between baseline and the second survey, intravenous
      paricalcitol significantly increased both the percentage of patients at target
      for PTH (P=0.033) and the percentage of patients at target for the combined
      endpoint PTH, calcium, and phosphate (P=0.001). The per-patient weekly
      pharmaceutical costs related to SHPT treatment, erythropoietin-stimulating agents
      and phosphate binders accounted for 186.32? and 219.94? at baseline for oral
      calcitriol and intravenous paricalcitol, respectively, while after 6 months, the
      costs were 180.51? and 198.79?, respectively. Either at the beginning of dialysis
      or 6 months later, the total cost of SHPT treatment was not significantly lower
      in the oral calcitriol group compared with the intravenous paricalcitol group,
      with a difference among groups that decreased by 46% between the two
      observations. The cost of erythropoietin stimulating agents at the second survey
      was lower (-22%) in the intravenous paricalcitol group than in the oral
      calcitriol group (132.13? versus 168.36?, respectively). CONCLUSION: Intravenous
      paricalcitol significantly increased the percentage of patients at target for the
      combined endpoint of PTH, calcium, and phosphate (P=0.001). The total cost of
      treatment for the patients treated with intravenous paricalcitol 6 months after
      entry to dialysis was not significantly higher than the cost for patients treated
      with oral calcitriol.

PMID- 25565881
TI  - Lyme borreliosis: a review of data on transmission time after tick attachment.
AB  - Lyme borreliosis is increasing rapidly in many parts of the world and is the most
      commonly occurring vector-borne disease in Europe and the USA. The disease is
      transmitted by ticks of the genus Ixodes. They require a blood meal at each stage
      of their life cycle and feed on a wide variety of wild and domestic animals as
      well as birds and reptiles. Transmission to humans is incidental and can occur
      during visits to a vector habitat, when host mammals and their associated ticks
      migrate into the urban environment, or when companion animals bring ticks into
      areas of human habitation. It is frequently stated that the risk of infection is
      very low if the tick is removed within 24-48 hours, with some claims that there
      is no risk if an attached tick is removed within 24 hours or 48 hours. A
      literature review has determined that in animal models, transmission can occur in
      <16 hours, and the minimum attachment time for transmission of infection has
      never been established. Mechanisms for early transmission of spirochetes have
      been proposed based on their presence in different organs of the tick. Studies
      have found systemic infection and the presence of spirochetes in the tick
      salivary glands prior to feeding, which could result in cases of rapid
      transmission. Also, there is evidence that spirochete transmission times and
      virulence depend upon the tick and Borrelia species. These factors support
      anecdotal evidence that Borrelia infection can occur in humans within a short
      time after tick attachment. 

PMID- 25565882
TI  - Treatment of localized neuropathic pain of different etiologies with the 5%
      lidocaine medicated plaster - a case series.
AB  - OBJECTIVE: To assess the efficacy and safety of the topical 5% lidocaine
      medicated plaster in the treatment of localized neuropathic pain. STUDY DESIGN:
      This was a case series at an Austrian pain clinic, using retrospective analysis.
      PATIENTS AND METHODS: Data of 27 patients treated for localized neuropathic pain
      with the 5% lidocaine medicated plaster were retrospectively analyzed. Assessment
      included changes in overall pain intensity, in intensity of different pain
      qualities, and of hyperalgesia and allodynia, and changes in sleep quality.
      RESULTS: Patients (17 female, ten male; mean age 53.4+/-11.4 years) presented
      mainly with dorsalgia (16 patients) or postoperative/posttraumatic pain (seven
      patients); one patient suffered from both. The mean overall pain intensity prior
      to treatment with lidocaine medicated plaster was 8.4+/-1.2 on the 11-point
      Likert scale. In the majority of cases, the lidocaine plaster was applied
      concomitantly with preexisting pain medication (81.5% of the patients). During
      the 6-month observation period, overall mean pain intensity was reduced by almost
      5 points (4.98) to 3.5+/-2.6. Substantial reductions were also observed for
      neuralgiform pain (5 points from 7.9+/-2.6 at baseline) and burning pain (3
      points from 5.2+/-4.1). Sleep quality improved from 4.6+/-2.6 at baseline to
      5.5+/-1.8. Stratification by pain diagnosis showed marked improvements in overall
      pain intensity for patients with dorsalgia or postoperative/posttraumatic pain.
      The lidocaine plaster was well tolerated. CONCLUSION: Overall, topical treatment
      with the 5% lidocaine medicated plaster was associated with effective pain relief
      and was well tolerated.

PMID- 25565884
TI  - Tapentadol prolonged release for severe chronic cancer-related pain:
      effectiveness, tolerability, and influence on quality of life of the patients.
AB  - BACKGROUND: Clinical trials have shown the efficacy and good tolerability of
      tapentadol prolonged release (PR) for severe chronic pain of different
      etiologies. This study investigated the influence of tapentadol PR on pain
      control and quality of life of patients with severe chronic cancer-related pain
      in routine clinical practice in Germany. PATIENTS AND METHODS: During a 3-month
      observation period, 45 physicians (mainly palliative care specialists) documented
      dosage and tolerability of tapentadol PR, previous and concomitant analgesic
      treatment, pain intensity, pain-related restrictions of daily activities and
      quality of life, and general state of health of 123 patients with chronic cancer
      related pain in the context of a prospective noninterventional study. RESULTS:
      All patients (mean age 63.9+/-13.2 years, 93.5% in constant pain) had received
      analgesic long-term treatment (42.3% strong opioids) prior to the start of
      tapentadol PR treatment. During the observation period, tapentadol PR
      significantly reduced the average pain intensity by 2.4 points (from a mean 6.1+/
      1.7 to 3.7+/-2.0, P<0.001); half of the patients (52%) achieved a pain score <=3
      at the end of observation. At the same time, mental and emotional well-being,
      pain-related impairments of daily activities, sleep quality, and quality of life
      improved, while the overall intake of analgesic concomitant medication could be
      reduced. Improvements in general state of health were significant (P<0.001).
      Overall, tapentadol PR was well tolerated. CONCLUSION: Good pain control with
      tapentadol PR was accompanied by markedly reduced pain-related mental and
      physical burden and quality of life improved. Overall, the general state of
      health of these patients with chronic cancer-related pain improved significantly
      despite the underlying illness.

PMID- 25565883
TI  - Clinical determinants of Lyme borreliosis, babesiosis, bartonellosis,
      anaplasmosis, and ehrlichiosis in an Australian cohort.
AB  - BACKGROUND: Borrelia burgdorferi is the causative agent of Lyme borreliosis. This
      spirochete, along with Babesia, Bartonella, Anaplasma, Ehrlichia, and the
      Rickettsia spp. are recognized tick-borne pathogens. In this study, the clinical
      manifestation of these zoonoses in Australia is described. METHODS: The clinical
      presentation of 500 patients over the course of 5 years was examined. Evidence of
      multisystem disease and cranial nerve neuropathy was sought. Supportive
      laboratory evidence of infection was examined. RESULTS: Patients from every state
      of Australia presented with a wide range of symptoms of disease covering multiple
      systems and a large range of time intervals from onset. Among these patients, 296
      (59%) were considered to have a clinical diagnosis of Lyme borreliosis and 273
      (54% of the 500) tested positive for the disease, the latter not being a subset
      of the former. In total, 450 (90%) had either clinical evidence for or laboratory
      proof of borrelial infection, and the great majority of cases featured
      neurological symptoms involving the cranial nerves, thus mimicking features of
      the disease found in Europe and Asia, as distinct from North America (where
      extracutaneous disease is principally an oligoarticular arthritis). Only 83
      patients (17%; number [n]=492) reported never leaving Australia. Of the 500
      patients, 317 (63%) had clinical or laboratory-supported evidence of coinfection
      with Babesia or Bartonella spp. Infection with A. phagocytophilum was detected in
      three individuals, and Ehrlichia chaffeensis was detected in one individual who
      had never traveled outside Australia. In the cohort, 30 (11%; n=279) had positive
      rickettsial serology. CONCLUSION: The study suggests that there is a considerable
      presence of borreliosis in Australia, and a highly significant burden of
      coinfections accompanying borreliosis transmission. The concept sometimes
      advanced of a "Lyme-like illness" on the continent needs to be re-examined as the
      clinical interplay between all these infections. Evidence is presented for the
      first report of endemic anaplasmosis and ehrlichiosis on the continent.

PMID- 25565885
TI  - Pregabalin for the treatment of postoperative pain: results from three controlled
      trials using different surgical models.
AB  - PURPOSE: To evaluate the efficacy and safety of pregabalin (150 or 300 mg/d) as
      an adjunctive therapy for the treatment of postoperative pain. PATIENTS AND
      METHODS: This study reports findings from three separate, multicenter,
      randomized, double-blind, placebo-controlled trials of adjunctive pregabalin for
      the treatment of postoperative pain. Patients underwent one of three categories
      of surgical procedures (one procedure per study): elective inguinal hernia repair
      (post-IHR); elective total knee arthroplasty (post-TKA); or total abdominal
      hysterectomy (posthysterectomy). The primary endpoint in each trial, mean worst
      pain over the past 24 hours, was assessed 24 hours post-IHR and posthysterectomy,
      and 48 hours post-TKA. Patients rated their pain on a scale from 0 to 10, with
      higher scores indicating greater pain severity. RESULTS: In total, 425 (post
      IHR), 307 (post-TKA), and 501 (posthysterectomy) patients were randomized to
      treatment. There were no statistically significant differences between the
      pregabalin and placebo groups with respect to the primary endpoint in any of the
      three trials. The least squares mean difference in worst pain, between 300 mg/d
      pregabalin and placebo, was -0.7 (95% confidence interval [CI] =-1.4, -0.1;
      Hochberg adjusted P=0.067) post-IHR; -0.34 (95% CI =-1.07, 0.39; P=0.362) post
      TKA; and -0.2 (95% CI =-0.66, 0.31; P=0.471) posthysterectomy. CONCLUSION: There
      were no significant differences between pregabalin and placebo with respect to
      the primary pain intensity measure in each of the three clinical trials. These
      studies encompass a large dataset (1,233 patients in total), and their results
      should be considered when assessing pregabalin's effectiveness in postoperative
      pain. Further studies are required to determine the potential pain-reducing
      benefit of pregabalin in the postoperative setting.

PMID- 25565887
TI  - Utilization of bone densitometry for prediction and administration of
      bisphosphonates to prevent osteoporosis in patients with prostate cancer without
      bone metastases receiving antiandrogen therapy.
AB  - BACKGROUND: Prostate cancer subjects with prostate-specific antigen (PSA) relapse
      who are treated with androgen deprivation therapy (ADT) are recommended to have
      baseline and serial bone densitometry and receive bisphosphonates. The purpose of
      this community population study was to assess the utilization of bone
      densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic
      prostate cancer. METHODS: A cohort study of men aged 65 years or older with non
      metastatic incident diagnoses of prostate cancer was obtained from the
      Surveillance Epidemiology End Results (SEER)-linked Medicare claims between 2004
      and 2008. Claims were used to assess prescribed treatment of ADT, bone
      densitometry, and bisphosphonates. RESULTS: A total of 30,846 incident prostate
      cancer cases receiving ADT and aged 65 years or older had no bone metastases;
      87.3% (n=26,935) on ADT did not receive either bone densitometry or
      bisphosphonate therapy. Three percent (n=931) of the cases on ADT received
      bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702)
      of the cases on ADT received bone densitometry without receiving intravenous
      bisphosphonates, while nearly 1% (0.90%, n=278) of the cases on ADT received both
      bone densitometry and bisphosphonates. Analysis showed treatment differed by
      patient characteristics. CONCLUSION: Contrary to the recommendations, bone
      densitometry and bisphosphonate therapy are underutilized in men receiving ADT
      for non-metastatic prostate cancer.

PMID- 25565888
TI  - Using registries to identify type 2 diabetes patients.

PMID- 25565886
TI  - Minimizing second cancer risk following radiotherapy: current perspectives.
AB  - Secondary cancer risk following radiotherapy is an increasingly important topic
      in clinical oncology with impact on treatment decision making and on patient
      management. Much of the evidence that underlies our understanding of secondary
      cancer risks and our risk estimates are derived from large epidemiologic studies
      and predictive models of earlier decades with large uncertainties. The modern era
      is characterized by more conformal radiotherapy technologies, molecular and
      genetic marker approaches, genome-wide studies and risk stratifications, and
      sophisticated biologically based predictive models of the carcinogenesis process.
      Four key areas that have strong evidence toward affecting secondary cancer risks
      are 1) the patient age at time of radiation treatment, 2) genetic risk factors,
      3) the organ and tissue site receiving radiation, and 4) the dose and volume of
      tissue being irradiated by a particular radiation technology. This review
      attempts to summarize our current understanding on the impact on secondary cancer
      risks for each of these known risk factors. We review the recent advances in
      genetic studies and carcinogenesis models that are providing insight into the
      biologic processes that occur from tissue irradiation to the development of a
      secondary malignancy. Finally, we discuss current approaches toward minimizing
      the risk of radiation-associated secondary malignancies, an important goal of
      clinical radiation oncology. 

PMID- 25565890
TI  - The optimal hormonal replacement modality selection for multiple organ
      procurement from brain-dead organ donors.
AB  - The management of brain-dead organ donors is complex. The use of inotropic agents
      and replacement of depleted hormones (hormonal replacement therapy) is crucial
      for successful multiple organ procurement, yet the optimal hormonal replacement
      has not been identified, and the statistical adjustment to determine the best
      selection is not trivial. Traditional pair-wise comparisons between every pair of
      treatments, and multiple comparisons to all (MCA), are statistically
      conservative. Hsu's multiple comparisons with the best (MCB) - adapted from the
      Dunnett's multiple comparisons with control (MCC) - has been used for selecting
      the best treatment based on continuous variables. We selected the best hormonal
      replacement modality for successful multiple organ procurement using a two-step
      approach. First, we estimated the predicted margins by constructing generalized
      linear models (GLM) or generalized linear mixed models (GLMM), and then we
      applied the multiple comparison methods to identify the best hormonal replacement
      modality given that the testing of hormonal replacement modalities is
      independent. Based on 10-year data from the United Network for Organ Sharing
      (UNOS), among 16 hormonal replacement modalities, and using the 95% simultaneous
      confidence intervals, we found that the combination of thyroid hormone, a
      corticosteroid, antidiuretic hormone, and insulin was the best modality for
      multiple organ procurement for transplantation. 

PMID- 25565889
TI  - Validation of the danish national diabetes register.
AB  - The Danish National Diabetes Register (NDR) was established in 2006 and builds on
      data from Danish health registers. We validated the content of NDR, using full
      information from the Danish National Patient Register and data from the
      literature. Our study indicates that the completeness in NDR is >=95% concerning
      ascertainment from data sources specific for diabetes, ie, prescriptions with
      antidiabetic drugs and diagnoses of diabetes in the National Patient Register.
      Since the NDR algorithm ignores diabetes-related hospital contacts terminated
      before 1990, the establishment of the date of inclusion is systematically delayed
      for >=10% of the registrants in general and for >=30% of the inclusions before
      1997 in particular. This bias is enhanced for ascertainment by chiropody services
      and by frequent measurements of blood glucose because the date of reimbursement
      of services, rather than the date of encounter, has been taken as the date of
      inclusion in NDR. We also find that some 20% of the registrations in NDR may
      represent false positive inclusions of persons with frequent measurements of
      blood glucose without having diabetes. We conclude that NDR is a novel initiative
      to support research in the epidemiological and public health aspects of diabetes
      in Denmark, but we also present a list of recommended changes for improving
      validity, by reducing the impact of current sources of bias and
      misclassifications. 

PMID- 25565891
TI  - Incorporating alternative design clinical trials in network meta-analyses.
AB  - INTRODUCTION: Network meta-analysis (NMA) is an extension of conventional
      pairwise meta-analysis that allows for simultaneous comparison of multiple
      interventions. Well-established drug class efficacies have become commonplace in
      many disease areas. Thus, for reasons of ethics and equipoise, it is not
      practical to randomize patients to placebo or older drug classes. Unique
      randomized clinical trial designs are an attempt to navigate these obstacles.
      These alternative designs, however, pose challenges when attempting to
      incorporate data into NMAs. Using ulcerative colitis as an example, we illustrate
      an example of a method where data provided by these trials are used to populate
      treatment networks. METHODS: We present the methods used to convert data from the
      PURSUIT trial into a typical parallel design for inclusion in our NMA. Data were
      required for three arms: golimumab 100 mg; golimumab 50 mg; and placebo.
      Golimumab 100 mg induction data were available; however, data regarding those
      individuals who were nonresponders at induction and those who were responders at
      maintenance were not reported, and as such, had to be imputed using data from the
      rerandomization phase. Golimumab 50 mg data regarding responses at week 6 were
      not available. Existing relationships between the available components were used
      to impute the expected proportions in this missing subpopulation. Data for
      placebo maintenance response were incomplete, as all induction nonresponders were
      assigned to golimumab 100 mg. Data from the PURSUIT trial were combined with ACT
      1 and ULTRA-2 trial data to impute missing information. DISCUSSION: We have
      demonstrated methods for converting results from alternative study designs to
      more conventional parallel randomized clinical trials. These conversions allow
      for indirect treatment comparisons that are informed by a wider array of
      evidence, adding to the precision of estimates.

PMID- 25565892
TI  - Parental celiac disease and risk of asthma in offspring: a Danish nationwide
      cohort study.
AB  - OBJECTIVE: The incidences of celiac disease (CD) and asthma are increasing and
      the two conditions are associated in individuals. Risk of asthma may be passed on
      to the next generation through shared risk factors. We examined whether parental
      CD is associated with risk of asthma in offspring. METHODS: We conducted a
      population-based Danish nationwide cohort study, using medical databases,
      covering the period 1 January 1979 to 31 December 2009. For each child with a
      parental history of CD, we randomly sampled 100 children without this history
      from the children born in the same calendar year. We used Cox proportional
      hazards regression to estimate incidence rate ratios for asthma, adjusting for
      measured covariates. RESULTS: We identified 1,107 children with a parental
      history of CD and 110,700 children without this parental history. During up to 32
      years of follow-up, 6,125 children received a hospital diagnosis of asthma. The
      adjusted incidence rate ratio for asthma associated with a parental history of CD
      was 1.09 (95% confidence interval: 0.86-1.39) and was similar for maternal and
      paternal CD. Inclusion of asthma-medication in the definition of asthma did not
      substantially change the results. CONCLUSION: There was no convincing evidence of
      an increased risk of asthma among offspring of parents with CD.

PMID- 25565893
TI  - Use of palivizumab is underestimated in the Swedish Prescribed Drug Register -
      implications for register-based drug studies.
AB  - BACKGROUND: Register studies are a valuable tool, when monitoring the safety of
      drugs. The Swedish Prescribed Drug Register (PDR) was established in 2005 and
      keeps records of all prescribed drugs dispensed in community pharmacies. Drugs
      prescribed in-hospital are not registered on an individual level, which may
      hamper the validity of register-based studies on drugs potentially administered
      in-hospital. OBJECTIVE: The objective was to assess the ability of the PDR to
      identify children treated with the monoclonal antibody palivizumab, which is used
      for prophylaxis against respiratory syncytial virus (RSV) infection in children.
      METHODS: Palivizumab exposure as filled prescriptions recorded in the PDR was
      assessed by indication of treatment (preterm-born children, bronchopulmonary
      dysplasia, or hemodynamically significant heart disease) and presented as numbers
      and proportions. For a random sample of children with an indication for treatment
      and without record of palivizumab exposure in the drug register, numbers and
      proportions by indication of treatment as noted in medical records were
      presented. The extent of underreporting in the drug register was estimated by
      indication for treatment. RESULTS: Through the national health registers, 2,317
      children were identified as being at risk for severe infection with RSV infection
      and 75% had no records indicating palivizumab exposure in the PDR. In a random
      sample of 176 children at high risk for RSV infection and with no records of
      palivizumab prescription fills in the PDR, 47% had been treated with palivizumab
      according to medical records. The PDR underestimated palivizumab treatment with
      49% in children born preterm, 42% in children with bronchopulmonary dysplasia,
      and 23% in those with a hemodynamically significant heart disease. CONCLUSION:
      Our findings underline the need of improving the information in the Swedish
      national registers concerning drugs administered in-hospital.

PMID- 25565894
TI  - Presurgical nasoalveolar remodeling - an experience in the journey of cleft lip
      and palate.
AB  - AIMS AND OBJECTIVES: To assess the effect of presurgical nasoalveolar molding
      (PNAM) therapy in the management of patients with nonsyndromic unilateral cleft
      lip and palate (UCLP). MATERIAL AND METHOD: Ten patients with UCLP treated from
      2009 to 2012. The initiation for PNAM treatment was 7 days and the average time
      of the treatment was 175 days. Measurements on patients and of casts were made,
      and statistical analysis was used to evaluate the changes in pre- and
      posttreatment measurements. RESULTS: Subsequent to PNAM treatment, there was a
      statistically considerable rise in cleft nostril height and columellar width.
      There was reduction in both intraoral cleft width and columellar deviation, which
      was significant statistically. CONCLUSION: PNAM treatment reduces alveolar cleft
      width. It enhances symmetry of the nose by changing columellar angulation,
      preserving alar width bilaterally, gaining height of the nostril on the affected
      side, and increasing columellar length.

PMID- 25565895
TI  - Ability of Saudi mothers to appropriately and accurately use dosing devices to
      administer oral liquid medications to their children.
AB  - BACKGROUND: Most liquid medications are packaged with administration devices,
      which may be used inappropriately or inaccurately, and sometimes are not used at
      all. Because of the importance of their proper use for children's health, this
      study was designed to assess Saudi mothers' experiences with measuring cups,
      syringes, and droppers for oral liquid medications; to compare accuracy of dosing
      across these devices; and to determine the effects of mothers' education statuses
      and pharmacist counseling on dosing accuracy. METHODS: This was a cross-sectional
      study in which mothers were observed as they used a set of commonly available
      dosing devices which are a dosing cup, syringe, and dropper. Interviews were
      conducted in the outpatient pharmacy waiting area in several tertiary hospitals
      and primary clinics in Riyadh, Saudi Arabia between March and April 2013. Saudi
      women who were mothers of children aged 12 years old or younger and who gave
      their consent were eligible. Caregivers other than mothers and subjects with
      vision problems or cognitive/physical disabilities were excluded. We gathered
      demographic information such as age, number of children, and education status.
      Subjects were asked if they had had counseling on how to use measuring devices
      and which device they preferred. Then, the mothers were required to demonstrate
      how to measure 5 mL of paracetamol (acetaminophen) syrup using a cup and a
      syringe and 1 mL of paracetamol syrup using a dropper. Dosing errors were
      evaluated visually as overdosing, underdosing, or no error (if the dose was
      accurate). The data were entered into Microsoft Excel and evaluated using Stata
      11.1. Logistic regression was employed to determine relationships. RESULTS: The
      results revealed that 58% of participants measured an accurate dose of
      paracetamol using the oral dosing syringe versus 50% of participants using the
      dropper and 51% using the dosing cup. In general, participants measured more than
      the intended dose with the dosing cup and less than the intended dose with the
      dropper. Furthermore, we found that dosing accuracy for each type of instrument
      was significantly influenced by the mothers' education status. Among the study
      participants, 77% had not had previous counseling on the use of liquid medication
      measuring devices. However, dosing errors were not affected by previous
      counseling. CONCLUSION: Among mothers using measuring devices, the most accurate
      doses were found to be measured with the use of the oral syringe, whereas the
      most errors were made with the use of the dropper. Moreover, education status had
      a significant effect on dosing errors. The use of a pictographic diagram could
      improve the mothers' dosing abilities and, thus, reduce dosing errors.

PMID- 25565898
TI  - Potential barriers to rapid testing for human immunodeficiency virus among a
      commuter population in Johannesburg, South Africa.
AB  - BACKGROUND: This study aimed to determine barriers to accessing human
      immunodeficiency virus (HIV) counseling and testing (HCT) services among a
      commuter population. METHODS: A cross-sectional, venue-based intercept survey was
      conducted. Participants were recruited during a 2-day community campaign at the
      Noord Street taxi rank in Johannesburg, South Africa. Data were collected using a
      self-administered questionnaire loaded onto an electronic data collection system
      and analyzed using Stata software. Factors contributing to barriers for HCT were
      modeled using multivariate logistic regression. RESULTS: A total of 1,146 (567
      male and 579 female) individuals were interviewed; of these, 51.4% were females.
      The majority (59.5%) were aged 25-35 years. Significant factors were age group
      (15-19 years), marital status (married), educational level (high school),
      distance to the nearest clinic (>30 km), area of employment/residence (outside
      inner city), and number of sexual partners (more than one). Participants aged 15
      19 years were more likely to report low-risk perception of HIV as a barrier to
      HCT (odds ratio [OR] 1.62; 95% confidence interval [CI] 1.01-2.59), the married
      were more likely to report low-risk perception of HIV as a barrier to HCT (OR
      1.49; 95% CI 1.13-1.96), and those living outside the inner city were more likely
      to report lack of partner support as a potential barrier (OR 1.94; 95% CI 1.34
      2.80), while those with a high school education were more likely to report poor
      health worker attitude as a potential barrier to HIV testing (OR 2.17; 95% CI
      1.36-3.45). CONCLUSION: Age, marital status, occupation, educational level, area
      of employment and residence, distance to the nearest clinic, and number of sexual
      partners were factors significantly associated with barriers to HIV testing in
      the study population. Future HIV intervention targeting this population need to
      be reinforced in order to enhance HIV testing while taking cognizance of these
      factors.

PMID- 25565899
TI  - Experiences of social oppression among men who have sex with men in a
      cosmopolitan city in Nigeria.
AB  - BACKGROUND: In several African countries, men who have sex with men (MSM) are
      becoming visible, as a result of which they are now victims of human rights
      violations. This has a negative effect on their ability to access services
      targeted at human immunodeficiency virus (HIV) prevention and care. The main
      objective of this study was to document the experiences of social oppression
      among MSM in Lagos State, Nigeria. METHODS: Simple random sampling was used to
      select three of the seven local government areas in Lagos State that had
      community centers. Snowball sampling was used to recruit 291 participants. The
      survey instrument was a pretested questionnaire. The results were presented as
      means and percentages. Univariate, bivariate, and multivariate analysis was
      carried out at P<0.05. RESULTS: The mean age of the participants was 25.3+/-4.6
      years, and the majority (66.0%) were currently single and not in a steady
      relationship. Half of the men self-identified as gay and about 48% as bisexual.
      Alcohol use occurred in 56.7% of the respondents, about a quarter (25.8%) smoked
      cigarettes, and 11.0% reported using hard drugs. The commonest acts of human
      rights violation and or violence reported were aggression 35.7%, alienation
      29.9%, verbal abuse 19.2%, physical abuse 17.9%, rape by a man 16.8%, and
      psychological abuse 20.3%. The predictors of human rights violation were level of
      education (adjusted odds ratio 2.6, P=0.019), marital status (adjusted odds ratio
      2.3, P=0.005), and sexual orientation (adjusted odds ratio 1.9, P=0.017). For
      physical and sexual abuse, MSM who consumed alcohol and were
      homosexual/transgender were at risk. CONCLUSION: This study showed that a high
      proportion of MSM had experienced various forms of human rights violation and
      abuse as a result of their sexual orientation/identity. There is a need to
      document and quantify these happenings, which can serve as an advocacy tool for
      reform.

PMID- 25565897
TI  - Managing dyslipidemia in HIV/AIDS patients: challenges and solutions.
AB  - Human immunodeficiency virus (HIV) is a chronic disease associated with
      dyslipidemia and insulin resistance. In addition, the administration of
      combination antiretroviral therapy is associated with an increase in the
      incidence of metabolic risk factors (insulin resistance, lipoatrophy,
      dyslipidemia, and abnormalities of fat distribution in HIV patients). HIV
      dyslipidemia is a common problem, and associated with an increase in incidence of
      cardiovascular disease. Further challenges in the management of HIV dyslipidemia
      are the presence of diabetes and metabolic syndrome, nonalcoholic fatty liver
      disease, hypothyroidism, chronic kidney disease, the risk of diabetes associated
      with statin administration, age and ethnicity, and early menopause in females.
      Dyslipidemia in patients with HIV is different from the normal population, due to
      the fact that HIV increases insulin resistance and HIV treatment not only may
      induce dyslipidemia but also may interact with lipid-lowering medication. The use
      of all statins (apart from simvastatin and lovastatin) is safe and effective in
      HIV dyslipidemia, and the addition of ezetimibe, fenofibrate, fish oil, and
      niacin can be used in statin-unresponsive HIV dyslipidemia. The management of
      dyslipidemia and cardiovascular disease risks associated with HIV is complex, and
      a certain number of patients may require management in specialist clinics run by
      specialist physicians in lipid disorders. Future research is needed to address
      best strategies in the management of hyperlipidemia with HIV infection. 

PMID- 25565900
TI  - Scientific research in obstetrics and gynecology: changes in the trends over
      three decades.
AB  - AIM: The aim of this work was to assess scientific research of master's and
      doctoral theses and essays in the Department of Obstetrics and Gynecology,
      Zagazig University, Egypt. MATERIALS AND METHODS: All master's and doctoral
      theses and essays since the foundation of Department of Obstetrics and
      Gynecology, Zagazig University, Egypt, in 1975 till end of 2012 were reviewed.
      RESULTS: A total of 703 theses and essays were reviewed. The important topics in
      the specialty of obstetrics and gynecology were covered and updated. Infertility,
      in vitro fertilization-embryo transfer (IVF-ET) and related techniques, and
      polycystic ovarian disease were the most common gynecologic topics (27.2%),
      followed by gynecologic oncology (18.5%). Preeclampsia was the most common
      obstetrics topic (18.8%), followed by issues of high-risk pregnancy, fetal growth
      restriction, and fetal well-being (11.6%). The number of researches that allow
      the candidates to learn skills was 183 and it was increased from 4.4% of all
      research in the period 1979-1988 to 33.2% in period 1989-2000 then slightly
      decreased to 31.2% in period 2001-2012. Ultrasonography was on the top and was
      present in 99 out of 183 (54.1%) followed by laparoscopy (30, 16.4%),
      hysteroscopy (25, 13.7%), IVF-ET and related techniques (16, 8.7%) and colposcopy
      (13, 7.1%) researches. Multi-disciplinary research was decreased by 61.7% in the
      period 2001-2012. Researches in academic fields were abandoned and in some
      clinically important areas like preeclampsia were decreased. CONCLUSION:
      Scientific research of master's and doctoral theses and essays was comprehensive,
      updated, and had some autonomy independent of plans. Research which enable the
      candidate to learn skills were increased on the expense of academic, clinical and
      multidisciplinary research. It could be recommended that plans for scientific
      research should be flexible and should leave a space for local departmental
      views. Proper training of residents during their rotation in these subspecialties
      may help to revive the lost interest in clinically important areas.

PMID- 25565901
TI  - Long-term efficacy, safety, and patient acceptability of ibandronate in the
      treatment of postmenopausal osteoporosis.
AB  - Several second-generation bisphosphonates (BPs) are approved in osteoporosis
      treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate
      synthase (FPPS) inhibition, hydroxyapatite affinity, compliance and adherence.
      The latter may be influenced by frequency and route of administration. A
      literature search using "ibandronate", "postmenopausal osteoporosis", "fracture",
      and "bone mineral density" (BMD) revealed 168 publications. The Phase III BONE
      study, using low dose 2.5 mg daily oral ibandronate demonstrated 49% relative
      risk reduction (RRR) in clinical vertebral fracture after 3 years. Non-vertebral
      fracture (NVF) reduction was demonstrated in a subgroup (pretreatment T-score <= 
      3.0; RRR 69%) and a meta-analysis of high annual doses (150 mg oral monthly or
      intravenous equivalent of ibandronate; RRR 38%). Hip fracture reduction was not
      demonstrated. Long-term treatment efficacy has been confirmed over 5 years. Long
      term safety is comparable to placebo over 3 years apart from flu-like symptoms
      which are more common with oral monthly and intravenous treatments. No cases of
      atypical femoral fracture or osteonecrosis of the jaw have been reported in
      randomized controlled trial studies. Ibandronate inhibits FPPS more than
      alendronate but less than other BPs which could explain rate of action onset.
      Ibandronate has a higher affinity for hydroxyapatite compared with risedronate
      but less than other BPs which could affect skeletal distribution and rate of
      action offset. High doses (150 mg oral monthly or intravenous equivalent) were
      superior to low doses (oral 2.5 mg daily) according to 1 year BMD change. Data
      are limited by patient selection, statistical power, under-dosing, and absence of
      placebo groups in high dose studies. Ibandronate treatment offers different doses
      and modalities of administration which could translate into higher adherence
      rates, an important factor when the two main limitations of BP treatment are
      initiation and adherence rates. However, lack of consistency in NVF reduction and
      absence of hip fracture data limits more generalized use of this agent. 

PMID- 25565902
TI  - Knowledge, practice, and barriers toward cervical cancer screening in Elmina,
      Southern Ghana.
AB  - AIMS: The aims of this study were: 1) to assess the level of knowledge of women
      about Pap smear tests, 2) to determine the practices of women regarding Pap smear
      tests, and 3) to determine the barriers to Pap smear tests in Elmina, Ghana.
      METHODS: A cross-sectional study was conducted with 392 randomly selected
      sexually active females aged 10-74 years using structured interview questions.
      The Institutional Review Board of the University of Cape Coast gave ethical
      approval for the study and informed consent was obtained from participants. Data
      were analyzed with SPSS software (v19.0) using frequencies, chi-square test, and
      exploratory factor analysis. RESULTS: The results revealed that 68.4% had never
      heard about cervical cancer, 93.6% had no knowledge on the risk factors, nine
      (2.3%) reported multiple sexual partners and being sexually active as risk
      factors, and 92% did not know about the prevention and treatment of cervical
      cancer. The majority (97.7%) had never heard of the Pap smear test. Only three
      (0.8%) women out of 392 had had a Pap smear test. Reasons for seeking a Pap smear
      test included referral, fear of cervical cancer, and radio campaigns. A
      significant association was found between institutional and personal barriers and
      having a Pap smear test. CONCLUSION: Comprehensive education on cervical cancer
      screening and removal of access barriers are critical in reducing risk associated
      with the disease and promoting women's health.

PMID- 25565903
TI  - Wound management with vacuum-assisted closure in postoperative infections after
      surgery for spinal stenosis.
AB  - OBJECTIVE: To evaluate the results of negative-pressure wound therapy (NPWT) in
      the treatment of surgical spinal site infections. MATERIALS AND METHODS: The use
      of NPWT in postoperative infections after dorsal spinal surgery (transforaminal
      lumbar interbody fusion plus posterior instrumentation) was studied
      retrospectively. From February 2011 to January 2012, six patients (females) out
      of 317 (209 females; 108 males) were readmitted to our clinic with surgical site
      infections on postoperative day 14 (range 9-19) and were treated with
      debridement, NPWT, and antibiotics. We evaluated the clinical and laboratory
      data, including the ability to retain the spinal hardware and recurrent
      infections. RESULTS: The incidence of deep postoperative surgical site infection
      was six (1.89%) patients (females) out of 317 patients (209 females; 108 males)
      at 1 year. All patients completed their wound NPWT regimen successfully. An
      average of 5.1 (range 3-8) irrigation and debridement sessions was performed
      before definitive wound closure. The mean follow-up period was 13 (range 12-16)
      months. No patient had a persistent infection requiring partial or total hardware
      removal. The hospital stay infection parameters normalized within an average of
      4.6 weeks. CONCLUSION: The study illustrates the usefulness of NPWT as an
      effective adjuvant treatment option for managing complicated deep spinal surgical
      wound infections.

PMID- 25565896
TI  - Treatment of bipolar disorders during pregnancy: maternal and fetal safety and
      challenges.
AB  - Treating pregnant women with bipolar disorder is among the most challenging
      clinical endeavors. Patients and clinicians are faced with difficult choices at
      every turn, and no approach is without risk. Stopping effective pharmacotherapy
      during pregnancy exposes the patient and her baby to potential harms related to
      bipolar relapses and residual mood symptom-related dysfunction. Continuing
      effective pharmacotherapy during pregnancy may prevent these occurrences for
      many; however, some of the most effective pharmacotherapies (such as valproate)
      have been associated with the occurrence of congenital malformations or other
      adverse neonatal effects in offspring. Very little is known about the
      reproductive safety profile and clinical effectiveness of atypical antipsychotic
      drugs when used to treat bipolar disorder during pregnancy. In this paper, we
      provide a clinically focused review of the available information on potential
      maternal and fetal risks of untreated or undertreated maternal bipolar disorder
      during pregnancy, the effectiveness of interventions for bipolar disorder
      management during pregnancy, and potential obstetric, fetal, and neonatal risks
      associated with core foundational pharmacotherapies for bipolar disorder. 

PMID- 25565906
TI  - In vivo measurements of regional hemoglobin oxygen saturation values and limb-to
      arm ratios of near-infrared spectroscopy for tissue oxygenation monitoring of
      lower extremities in healthy subjects.
AB  - OBJECTIVE: Near-infrared spectroscopy (NIRS) is a noninvasive technique that
      allows monitoring of regional hemoglobin oxygen saturation (rSO2) values and
      might have a role in the diagnosis of peripheral arterial disease. We assessed
      the reproducibility and inter-subject variability of rSO2 values and rSO2 limb-to
      arm ratios (LARs) in lower extremities of healthy subjects. METHODS: The rSO2
      values and rSO2 LARs were calculated in eight healthy subjects without peripheral
      arterial disease. The rSO2 values were measured at rest at six fixed spots at
      each lower limb and a reference spot at each upper arm. NIRS provided the rSO2
      values without involvement of any other processing technique. After measurements
      were completed, rSO2 LARs were calculated by dividing the rSO2 value of a lower
      extremity spot by the rSO2 value of the arm. Measurements were performed twice on
      1 day and repeated on 4 different days. RESULTS: Mean coefficients of variation
      of measurements of rSO2 values and rSO2 LARs at the same spot in the same subject
      were respectively less than 6% and 8% for every measurement spot over time.
      Coefficients of variation of measurements at the same spot between different
      subjects were less than 15% and 19% for every measurement spot respectively.
      CONCLUSION: NIRS is an easily applicable, noninvasive tool for measurement of
      tissue oxygenation of lower extremities in healthy subjects. The reproducibility
      of rSO2 values and rSO2 LARs at the same measurement spot in the same subject is
      good.

PMID- 25565904
TI  - Atherectomy devices: technology update.
AB  - Atherectomy is a procedure which is performed to remove atherosclerotic plaque
      from diseased arteries. Atherosclerotic plaques are localized in either coronary
      or peripheral arterial vasculature and may have different characteristics
      depending on the texture of the plaque. Atherectomy has been used effectively in
      treatment of both coronary and peripheral arterial disease. Atherectomy devices
      are designed differently to either cut, shave, sand, or vaporize these plaques
      and have different indications. In this article, current atherectomy devices are
      reviewed. 

PMID- 25565905
TI  - Transmyocardial revascularization devices: technology update.
AB  - Transmyocardial laser revascularization (TMR) emerged as treatment modality for
      patients with diffuse coronary artery disease not amendable to percutaneous or
      surgical revascularization. The procedure entails the creation of laser channels
      within ischemic myocardium in an effort to better perfuse these areas. Currently,
      two laser devices are approved by the US Food and Drug Administration for TMR -
      holmium:yttrium-aluminum-garnet and CO2. The two devices differ in regard to
      energy outputs, wavelengths, ability to synchronize with the heart cycle, and
      laser-tissue interactions. These differences have led to studies showing
      different efficacies between the two laser devices. Over 50,000 procedures have
      been performed worldwide using TMR. Improvements in angina stages, quality of
      life, and perfusion of the myocardium have been demonstrated with TMR. Although
      several mechanisms for these improvements have been suggested, evidence points to
      new blood vessel formation, or angiogenesis, within the treated myocardium, as
      the major contributory factor. TMR has been used as sole therapy and in
      combination with coronary artery bypass grafting. Clinical studies have
      demonstrated that TMR is both safe and effective in angina relief long term. The
      objective of this review is to present the two approved laser devices and
      evidence for the safety and efficacy of TMR, along with future directions with
      this technology. 

PMID- 25565908
TI  - Sex-specific differences in injury types among basketball players.
AB  - The purpose of the present study was to investigate sex-specific differences in
      injury types among basketball players. According to our database, during the 20
      year period between October 1991 and June 2011, 1,219 basketball players (640
      males and 579 females) consulted our sports medicine clinic; in total, 1,414
      injuries in basketball players (729 injuries in males and 685 injuries in
      females) were recorded. The mean age of patients was 19.6 years. The most common
      injury site was the knee, followed by the foot and ankle, lower back, and upper
      extremities. There was a higher proportion of female players presenting with a
      knee injury, compared with male players (50.4% vs 41.7%), and a lower proportion
      of female players presenting with an upper extremity injury (5.1% vs 9.7%). The
      proportion of anterior cruciate ligament injury in the 10-19-year-old age group
      was higher among female players than among male players (45.9% vs 22.1%), while
      the proportions of Osgood-Schlatter disease in the 10-19-year-old age group and
      jumper's knee (patellar and femoral tendinopathy) in the 20-29-year-old age group
      were higher among male players than among female players (12.5% vs 1.8% and 14.6%
      vs 3.7%, respectively). However, the proportions of other injuries did not differ
      significantly between male and female players. The present observational study,
      which was performed using a retrospective case-series design, showed the
      existence of sex-specific differences in knee injuries sustained while
      participating in basketball. 

PMID- 25565907
TI  - The everolimus-eluting Xience stent in small vessel disease: bench, clinical, and
      pathology view.
AB  - Coronary artery disease (CAD) is the leading cause of morbidity and mortality
      worldwide. The pathogenesis of CAD relates to the presence of atherosclerotic
      plaques in the coronary arteries, which are most frequently treated today by
      percutaneous coronary intervention. Small vessel disease treatment represents one
      third of all percutaneous coronary interventions with higher rates of restenosis
      and major adverse cardiac events. Initially, drug-eluting stents (DES) were
      developed to reduce in-stent restenosis, improving clinical outcomes and reducing
      the need for target vessel revascularization. However, late and very late stent
      thrombosis emerged as a new problem compromising DES's long-term results. The
      cobalt-chromium everolimus-eluting stent (CoCr-EES) represents the results of an
      evolutionary process in DES technology aimed at improving the shortcomings of
      first-generation DES. Small vessel CAD has historically been an obstacle to long
      term patency following implantation of DES. Antirestenotic efficacy has been
      shown to be of high relevance in small vessels. Therefore, stent selection may
      play an important role in determining outcomes in this subgroup of patients. This
      article will review the performance of CoCr-EES in the treatment of small vessel
      CAD from preclinical, clinical, and pathology perspectives, and it will highlight
      the most important findings in this regard. 

PMID- 25565909
TI  - Alexithymia in eating disorders: therapeutic implications.
AB  - A high percentage of individuals affected by eating disorders (ED) achieve
      incomplete recovery following treatment. In an attempt to improve treatment
      outcome, it is crucial that predictors of outcome are identified, and
      personalized care approaches established in line with new treatment targets, thus
      facilitating patient access to evidence-based treatments. Among the psychological
      factors proposed as predictors of outcome in ED, alexithymia is of outstanding
      interest. The objective of this paper is to undertake a systematic review of the
      literature relating to alexithymia, specifically in terms of the implications for
      treatment of ED. In particular, issues concerning the role of alexithymia as a
      predictor of outcome and as a factor to be taken into account in the choice of
      treatment will be addressed. The effect of treatments on alexithymia will also be
      considered. A search of all relevant literature published in English using
      PubMed, PsycINFO, and Scopus databases was carried out on the basis of the
      following keywords: alexithymia, anorexia nervosa, bulimia nervosa, eating
      disorders, and treatment; no time limits were imposed. Despite the clinical
      relevance of alexithymia, the number of studies published on the above cited
      aspects is somewhat limited, and these studies are largely heterogeneous and
      feature significant methodological weaknesses. Overall, data currently available
      mostly correlate higher levels of alexithymia with a less favorable outcome in
      ED. Accordingly, alexithymia is seen as a relevant treatment target with the aim
      of achieving recovery of these patients. Treatments focusing on improving
      alexithymic traits, and specifically those targeting emotions, seem to show
      greater efficacy, although alexithymia levels often remain high even after
      specific treatment. Further investigations are needed to overcome the
      methodological limitations of previous studies, to understand the actual impact
      of alexithymia on ED outcome, and to allow more precise implications for
      treatment to be drawn. Additional research should also be undertaken to specify
      which of the alexithymic dimensions are specifically relevant to the course and
      outcome of ED, and to identify treatment protocols producing a significantly
      greater efficacy in ED patients with relevant alexithymic traits. 

PMID- 25565911
TI  - Responses of advanced directives by Jehovah's Witnesses on a gynecologic oncology
      service.
AB  - OBJECTIVES: To review the responses of advance directives signed by Jehovah's
      Witness patients prior to undergoing surgery at a gynecologic oncology service.
      STUDY DESIGN: A retrospective chart review of gynecologic oncology patients
      undergoing surgery at a bloodless surgery center from 1998-2007 was conducted.
      Demographic, pathologic, and clinical data were recorded. The proportion of
      patients who accepted and refused various blood-derived products was determined
      and was compared to previously published results from a similar study of labor
      and delivery unit patients. RESULTS: No gynecologic oncology patients agreed to
      accept transfusions of whole blood, red cells, white cells, platelets, or plasma
      under any circumstance, whereas 9.8% of pregnant patients accepted transfusion
      (P=0.0385). However, 98% of gynecologic oncology patients agreed to accept some
      blood products, including fractions such as albumin, immunoglobulins, and
      clotting factors, while only 39% of pregnant patients agreed (P<0.0001). In
      addition, all gynecologic oncology patients (100%) accepted intraoperative
      hemodilution, compared to 55% of pregnant patients (P<0.0001). CONCLUSION: Our
      results confirm the commonly held belief that the majority of Jehovah's Witness
      patients refuse to accept major blood components. However, Jehovah's Witness
      patients at a gynecologic oncology service will accept a variety of blood-derived
      products (minor fractions) and interventions designed to optimize outcomes when
      undergoing transfusion-free surgery. Patients presenting to a gynecologic
      oncology service respond differently to advanced directives related to bloodless
      surgery, as compared to patients from an obstetrical service.

PMID- 25565910
TI  - Clinical utility of lenalidomide in the treatment of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) represent a heterogeneous group of acquired
      clonal hematopoietic disorders characterized by peripheral blood cytopenias,
      paradoxical BM hypercellularity, ineffective hematopoiesis, and increased risk of
      leukemic transformation. Risk stratification, using different prognostic scores
      and markers, is at the core of MDS management. Deletion 5q [del(5q)] MDS is a
      distinct class of MDS characterized by the haploinsufficiency of specific genes,
      microRNAs, and proteins, which has been linked to increased sensitivity to the
      drug lenalidomide. Phase II and III clinical trials have demonstrated the
      efficacy of lenalidomide in improving clinical outcomes of patients with del(5q)
      MDS, including reduction in red blood cell transfusion requirements and
      improvements in quality of life. Lenalidomide has also demonstrated some activity
      in non-del(5q) lower-risk MDS as well as higher-risk MDS, especially in
      combination with other agents. In this paper, we review the pathogenesis of
      del(5q) MDS, the proposed mechanisms of action of lenalidomide, the major
      clinical trials that documented the activity of lenalidomide in different MDS
      populations, potential predictors of benefit from the drug and suggested
      mechanisms of resistance, and the use of combination strategies to expand the
      clinical utility of lenalidomide in MDS. 

PMID- 25565912
TI  - Confidence in dental care and public health competency during rural practice
      among new dental graduates in Thailand.
AB  - OBJECTIVE: The dental profession has played an important role in the development
      of the health system in Thailand. However, it is not known if dental graduates'
      standards of knowledge, skills, and capabilities are fulfilling the health needs
      of Thais. This study aimed to assess the level of confidence in dental public
      health competency among final-year dental students who graduated in 2013.
      METHODS: A cross-sectional survey was conducted among 571 new dental graduates
      who participated in an official meeting arranged by the Ministry of Public Health
      in 2013. Self-administered questionnaires were used for collecting data on their
      confidence levels in selected public-health competencies. Of the total graduates,
      72.5% anonymously responded to the questionnaire. Descriptive and inferential
      statistics, factor analysis, and stepwise regression were applied for data
      analysis. RESULTS: The majority of respondents expressed confidence in their
      ability to care for patients, but less confidence in public-health and
      administration competencies. The results also show that there was no significant
      association between demographic and educational profiles of respondents and
      confidence in their clinical competency. However, significantly more students who
      graduated from schools located outside Bangkok and vicinity rated themselves as
      competent in public health (coefficient = 0.333, P=0.021). CONCLUSION: New
      dentists who graduated from dental schools in Bangkok and vicinity had lower
      levels of confidence in their public-health competencies compared to those who
      graduated from dental schools outside Bangkok. Thus, working in rural areas after
      graduation could help new dentists gain more experience in rural practice,
      leading to higher confidence levels. The findings from this study could
      contribute to the improvement of the dental curriculum and contract-bonding
      policy to work in rural areas.

PMID- 25565913
TI  - What motivates surgeons to teach dissection anatomy to medical students and
      surgical trainees?
AB  - INTRODUCTION: Although a fading tradition in some institutions, having clinicians
      teach anatomy by whole-body dissection provides a clinical context to
      undergraduate and postgraduate medical students, increasing their depth of
      learning. The reasons for a clinician's motivation to teach may be articulated in
      accordance with self-determination theory (SDT). SDT proposes that for
      individuals to be intrinsically motivated, three key elements are needed: 1)
      autonomy, 2) competence, and 3) relatedness. MATERIALS AND METHODS: Data were
      collected through semistructured interviews with eight surgeons who were
      supervisors/facilitators in the anatomy by whole-body dissection course for
      undergraduate students in the Bachelor of Medicine, Bachelor of Surgery program
      and postgraduate students in the Master of Surgery program at the University of
      Sydney. Qualitative analysis methods were used to code and categorize data into
      themes. RESULTS: Our study used SDT as a conceptual framework to explore
      surgeons' motivation to supervise students in the anatomy by whole-body
      dissection courses. Elements that facilitated their desire to teach included
      satisfaction derived from teaching, a sense of achievement in providing students
      with a clinical context, a strong sense of community within the dissection
      courses, and a sense of duty to the medical/surgical profession and to patient
      welfare. CONCLUSION: The surgeons' motivation for teaching was largely related to
      their desire to contribute to the training of the next generation of doctors and
      surgeons, and ultimately to future patient welfare.

PMID- 25565914
TI  - Back to basics: tackling the challenges to bedside teaching.

PMID- 25565915
TI  - Developing a new experimental system for an undergraduate laboratory exercise to
      teach theories of visuomotor learning.
AB  - Humans have a flexible motor ability to adapt their movements to changes in the
      internal/external environment. For example, using arm-reaching tasks, a number of
      studies experimentally showed that participants adapt to a novel visuomotor
      environment. These results helped develop computational models of motor learning
      implemented in the central nervous system. Despite the importance of such
      experimental paradigms for exploring the mechanisms of motor learning, because of
      the cost and preparation time, most students are unable to participate in such
      experiments. Therefore, in the current study, to help students better understand
      motor learning theories, we developed a simple finger-reaching experimental
      system using commonly used laptop PC components with an open-source programming
      language (Processing Motor Learning Toolkit: PMLT). We found that compared to a
      commercially available robotic arm-reaching device, our PMLT accomplished similar
      learning goals (difference in the error reduction between the devices, P = 0.10).
      In addition, consistent with previous reports from visuomotor learning studies,
      the participants showed after-effects indicating an adaptation of the motor
      learning system. The results suggest that PMLT can serve as a new experimental
      system for an undergraduate laboratory exercise of motor learning theories with
      minimal time and cost for instructors. 

PMID- 25565916
TI  - Students apply research methods to consumer decisions about cognitive enhancing
      drinks.
AB  - The goal of this class project was to provide students with a hands-on research
      experience that allowed autonomy, but eliminated duplication of effort and could
      be completed within one semester. Our resources were limited to a small supply
      budget and an introductory psychology subject pool. Six students from a
      behavioral neuroscience class tested claims made by a drink company that their
      product improves cognitive function. The students each chose a cognitive task for
      their part of the project. The tasks included the Donders Reaction Time Task, the
      Stroop Task, the Raven's Progressive Matrices, a short-term memory span test, the
      Rey-Osterrieth Complex Figure Test and a simple measure of prefrontal EEG
      activity. Participants were randomly assigned to an experimental or control
      drink. The experimental group received the putative cognitive enhancing drink and
      the control group received a placebo drink that was very similar in color and
      taste. The two drinks shared no active ingredients. Results suggest that the
      putative cognitive enhancing drink did not improve performance on any of the
      tasks and decreased performance on the short-term memory task. These findings are
      discussed in regard to implications for consumers as well as further research
      into supplements and their ability to improve cognitive performance. Each student
      presented his/her results at a university-wide research conference. This project
      provided a rich experience in which students had the opportunity to carry out a
      research project from conception to presentation. 

PMID- 25565917
TI  - "Thinking like a Neuroscientist": Using Scaffolded Grant Proposals to Foster
      Scientific Thinking in a Freshman Neuroscience Course.
AB  - Learning and practicing scientific inquiry is an essential component of a STEM
      education, but it is often difficult to teach to novices or those outside of a
      laboratory setting. To promote scientific thinking in a freshmen introductory
      neuroscience course without a lab component, we developed a series of learning
      activities and assignments designed to foster scientific thinking through the use
      of scientific grant proposals. Students wrote three short grant proposals on
      topics ranging from molecular to cognitive neuroscience during a 10-week class
      (one quarter). We made this challenging and advanced task feasible for novice
      learners through extensive instructional scaffolding, opportunity for practice,
      and frequent peer and instructor feedback. Student and instructor reports
      indicate that the assignments were highly intellectually engaging and that they
      promoted critical thinking, a deeper understanding of neuroscience material, and
      effective written communication skills. Here we outline the mechanics of the
      assignment, student and instructor impressions of learning outcomes, and the
      advantages and disadvantages of implementing this approach. 

PMID- 25565919
TI  - Engaging undergraduate summer research students and faculty in a regional
      neuroscience network.
AB  - Students who engage in experiential research programs and who form communities of
      learning are more likely to persist in Science, Technology, Engineering, and Math
      (STEM) programs. Faculty who collaborate are more likely to publish and to stay
      engaged in their field. With funding from the Great Lakes Colleges Association
      (GLCA) Expanding Collaboration Initiative, we engaged in a series of summer
      seminars with neuroscience faculty and their research students at five regional
      institutions, the College of Wooster, Ohio Wesleyan University, Earlham College,
      Oberlin College and Kenyon College. Our goals were to provide an opportunity for
      faculty and students to learn about the methods used in the labs at these
      institutions, to increase collaborative relationships across these institutions,
      to develop a community of learning among participating students, and to provide
      students with professional development opportunities. Pre- and post-assessment
      data indicate knowledge gains in demonstrated methods and increased comfort
      performing the methods with supervision or collaboration. In addition, several
      collaborative relationships were formed and significant assistance with planning,
      materials, and/or apparatus was provided across institutions. In open-ended post
      experience questions, students indicated valuing the relationships formed with
      other students in this community of learning. We will continue this program with
      continued funding through the GLCA Expanding Collaboration Initiative and
      submission of a multi-center National Science Foundation Research Experience for
      Undergraduates grant and encourage others to engage in similar practices at their
      own institutions. 

PMID- 25565918
TI  - A proposal for undergraduate students' inclusion in brain awareness week:
      promoting interest in curricular neuroscience components.
AB  - Brain Awareness Week (BAW) is a global campaign aimed at raising awareness of
      neuroscience and the progress and benefits of brain research. Our proposal was to
      include undergraduate physiology students in the organization and presentation of
      BAW activities. In this sense, we proposed the BAW as a neurophysiology teaching
      strategy. BAW 2013 occurred between March 11-17, and physiology students in the
      Nursing, Pharmacy and Physiotherapy programs of our university were involved in
      the organization of and participation in the activities. To evaluate student
      perceptions of their participation, a questionnaire was used to establish whether
      their involvement increased their interest in physiology/neuroscience. Our
      results indicated that this strategy was successful and increased the students'
      interest in neuroscience and physiology. In addition a survey of undergraduate
      and graduate students participating in BAW established their interest in the
      various activities available. The attention and reaction time workshop and the
      neuroanatomy workshop were the most popular of the eight activities available. 

PMID- 25565921
TI  - K-12 Neuroscience Education Outreach Program: Interactive Activities for
      Educating Students about Neuroscience.
AB  - The University of New England's Center for Excellence in the Neurosciences has
      developed a successful and growing K-12 outreach program that incorporates
      undergraduate and graduate/professional students. The program has several goals,
      including raising awareness about fundamental issues in neuroscience,
      supplementing science education in area schools and enhancing undergraduate and
      graduate/professional students' academic knowledge and skill set. The outreach
      curriculum is centered on core neuroscience themes including: Brain Safety,
      Neuroanatomy, Drugs of Abuse and Addiction, Neurological and Psychiatric
      Disorders, and Cognition and Brain Function. For each theme, lesson plans were
      developed based upon interactive, small-group activities. Additionally, we've
      organized our themes in a "Grow-up, Grow-out" approach. Grow-up refers to
      returning to a common theme, increasing in complexity as we revisit students from
      early elementary through high school. Grow-out refers to integrating other
      scientific fields into our lessons, such as the chemistry of addiction, the
      physics of brain injury and neuronal imaging. One of the more successful
      components of our program is our innovative team-based model of curriculum
      design. By creating a team of undergraduate, graduate/professional students and
      faculty, we create a unique multi-level mentoring opportunity that appears to be
      successful in enhancing undergraduate students' skills and knowledge. Preliminary
      assessments suggest that undergraduates believe they are enhancing their content
      knowledge and professional skills through our program. Additionally, we're having
      a significant, short-term impact on K-12 interest in science. Overall, our
      program appears to be enhancing the academic experience of our undergraduates and
      exciting K-12 students about the brain and science in general. 

PMID- 25565922
TI  - The reviews are in: resources for undergraduate neuroscience education.

PMID- 25565920
TI  - Recording field potentials from zebrafish larvae during escape responses.
AB  - Among vertebrates, startle responses are a ubiquitous method for alerting, and
      avoiding or escaping from alarming or dangerous stimuli. In zebrafish larvae,
      fast escape behavior is easily evoked through either acoustic or tactile stimuli.
      For example, a light touch to the head will excite trigeminal neurons that in
      turn excite a large reticulospinal neuron in the hindbrain called the Mauthner
      cell (M-cell). The M-cell action potential then travels down the contralateral
      trunk of the larva exciting motoneurons, which subsequently excite the entire
      axial musculature, producing a large amplitude body bend away from the source of
      the stimulus. This body conformation is known as the "C-bend" due to the shape of
      the larva during the behavior. As a result of the semi-synchronized activation of
      the M-cell, the population of motor neurons, and the axial trunk muscles, a large
      field potential is generated and can be recorded from free-swimming or fixed
      position larvae. Undergraduate laboratories that record field potentials during
      escape responses in larval zebrafish are relatively simple to setup and allow
      students to observe and study the escape reflex circuit. Furthermore, by testing
      hypotheses, analyzing data and writing journal-style laboratory reports, students
      have multiple opportunities to learn about many neuroscience topics including
      vertebrate reflexes; sensory transduction; synaptic-, neuro-, and muscle
      physiology; the M-cell mediated escape response; and the zebrafish as a model
      organism. Here, we detail the equipment, software, and recording setup necessary
      to observe field potentials in an undergraduate teaching lab. Additionally, we
      discuss potential advanced laboratory exercises and pedagogical outcomes.
      Finally, we note possible low-cost alternatives for recording field potentials. 

PMID- 25565923
TI  - Sipuleucel-T in the treatment of prostate cancer: an evidence-based review of its
      place in therapy.
AB  - Metastatic castration-resistant prostate cancer is the lethal form of cancer of
      the prostate. Five new agents that prolong survival in this group have emerged in
      the past 5 years, and sipuleucel-T is among them. Sipuleucel-T is the only
      immunotherapy shown to improve survival in prostate cancer. It is currently
      indicated in asymptomatic or mildly symptomatic patients, as it has never shown a
      direct cancer effect. This paper describes the process of creating the sipuleucel
      T product from the manufacturing and patient aspects. It discusses the four
      placebo-controlled, randomized clinical trials (RCTs) of sipuleucel-T, focusing
      on survival and adverse events. There are three RCTs in metastatic castration
      resistant prostate cancer, all of which showed improved overall survival without
      meaningful decreases in symptoms, tumor volumes, or prostate-specific antigen
      levels. One RCT in castration-sensitive, biochemically relapsed prostate cancer
      attempted to find a decrease in biochemical failure, but that endpoint was not
      reached. Adverse events in all four of these studies centered around cytokine
      release. This paper also reviews a Phase II study of sipuleucel-T given
      neoadjuvantly that speaks to its mechanism of action. Additionally, there is a
      registry study of sipuleucel-T that has been used to evaluate immunological
      parameters of the product in men >=80 years of age and men who had previously
      been treated with palliative radiation. Attempts to find early markers of
      response to sipuleucel-T are described. Further ongoing studies that explore the
      efficacy of sipuleucel-T in combination with immune checkpoint inhibitors and
      second-generation hormonal therapies that are summarized. Finally, the only
      published economic analysis of sipuleucel-T is discussed. 

PMID- 25565924
TI  - All humans, great or small, short or tall.

PMID- 25565925
TI  - Common somatic alterations identified in maffucci syndrome by molecular
      karyotyping.
AB  - Maffucci syndrome (MS) is a rare congenital disorder characterized by multiple
      central cartilaginous tumors (enchondromas) in association with cutaneous spindle
      cell hemangiomas. These patients have a high incidence of malignant
      transformation. No familial case is known and the etiopathogenic cause remains
      unknown. In enchondromatosis (Ollier disease, OD), which is comprised of
      enchondromas only, 4 mutations in the PTHR1 gene have been identified in 4
      patients; 3 were somatic and 1 was germline. No PTHR1 mutations have been
      detected in MS, whereas somatic IDH1 and, more rarely, IDH2 mutations have been
      observed in 77% of patients with MS and 81% of patients with OD. These genetic
      alterations are shared with other tumors, including glioma, leukemia and
      carcinoma. To search for underlying somatic genomic causes, we screened MS
      tissues using Affymetrix SNP-chips. We looked for CNVs, LOH and uniparental
      isodisomy (UPID) by performing pairwise analyses between allelic intensities in
      tumoral DNA versus the corresponding blood-extracted DNA. While common
      chromosomal anomalies were absent in constitutional DNA, several shared CNVs were
      identified in MS-associated tumors. The most frequently encountered somatic
      alterations were localized in 2p22.3, 2q24.3 and 14q11.2, implicating these
      chromosomal rearrangements in the formation of enchondromas and spindle cell
      hemangiomas in MS. In one chondrosarcoma specimen, large amplifications and/or
      deletions were observed in chromosomes 3, 6, 9, 10, 12, 13, and 19. Some of these
      genetic changes have been reported in other chondrosarcomas suggesting an
      etiopathogenic role. No LOH/UPID was observed in any Maffucci tissue. Our
      findings identify frequent somatic chromosomal rearrangements on 2p22.3, 2q24.3
      and 14q11.2, which may unmask mutations leading to the lesions pathognomonic of
      MS. 

PMID- 25565926
TI  - Novel Deletion of SERPINF1 Causes Autosomal Recessive Osteogenesis Imperfecta
      Type VI in Two Brazilian Families.
AB  - Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI
      cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1,
      FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for
      this form of the disease. PEDF is a secreted glycoprotein of the serpin
      superfamily that maintains bone homeostasis and regulates osteoid mineralization,
      and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860).
      Here, we report a consanguineous Brazilian family in which multiple individuals
      from at least 4 generations are affected with a severe form of OI, and we also
      report an unrelated individual from the same small city in Brazil with a similar
      but more severe phenotype. In both families the same homozygous SERPINF1 19-bp
      deletion was identified which is not known in the literature yet. We described
      intra- and interfamilial clinical and radiological phenotypic variability of OI
      type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a
      founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in
      the literature are reviewed. 

PMID- 25565927
TI  - A mouse splice-site mutant and individuals with atypical chromosome 22q11.2
      deletions demonstrate the crucial role for crkl in craniofacial and pharyngeal
      development.
AB  - The 22q11.2 deletion syndrome (22q11DS) is thought to be a contiguous gene
      syndrome caused by haploinsufficiency for a variable number of genes with
      overlapping function during the development of the craniofacial, pharyngeal and
      cardiac structures. The complexity of genetic and developmental anomalies
      resulting in 22q11DS has made attributing causation to specific genes difficult.
      The CRKL gene resides within the common 3-Mb region, most frequently affected in
      22q11DS, and has been shown to play an essential role in the development of
      tissues affected in 22q11DS. Here, we report the characterisation of a mouse
      strain we named 'snoopy', harbouring a novel Crkl splice-site mutation that
      results in a loss of Crkl expression. The snoopy strain exhibits a variable
      phenotype that includes micrognathia, pharyngeal occlusion, aglossia and
      holoprosencephaly, and altered retinoic acid and endothelin signalling. Together,
      these features are reminiscent of malformations occurring in auriculocondylar
      syndrome and agnathia-otocephaly complex, 2 conditions not previously associated
      with the CRKL function. Comparison of the features of a cohort of patients
      harbouring small 22q11.2 deletions centred over the CRKL gene, but sparing TBX1,
      highlights the role of CRKL in contributing to the craniofacial features of
      22q11DS. These analyses demonstrate the central role of Crkl in regulating
      signalling events in the developing oropharyngeal complex and its potential to
      contribute to dysmorphology. 

PMID- 25565928
TI  - Challenges in clinical diagnosis of williams-beuren syndrome in sub-saharan
      africans: case reports from cameroon.
AB  - Williams-Beuren syndrome (WBS) is a rare neurodevelopmental condition caused by a
      recurrent chromosomal microdeletion involving about 28 contiguous genes at
      7q11.23. Most patients display a specific congenital heart defect, characteristic
      facial features, a particular behavior, and intellectual disability. Cases from
      sub-Saharan Africa have been seldom reported. The present study describes 3
      Cameroonian patients affected by WBS, aged 19 months, 13 and 14 years, in whom
      the diagnosis was confirmed by fluorescent in situ hybridization (FISH) and
      comparative genomic hybridization (CGH). The first patient presented with a
      congenital heart defect, the second and third with learning difficulties as well
      as developmental and behavioral issues. In the latter 2 cases, the facial
      phenotypes were similar to those of the unaffected population with the same
      ethnic background. However, the cardiovascular anomalies and friendly behavioral
      attitudes led to suspicion of WBS. FISH revealed the deletion of the WBS critical
      region in the first patient, and array-CGH detected a heterozygous ~1.4-Mb
      deletion in the 7q11.23 region in the second and third patient. This preliminary
      report suggests that for sub-Saharan Africans clinical suspicion of WBS could be
      mostly based on behavioral phenotype and structural heart defects, and less on
      the classical facial dysmorphic signs. 

PMID- 25565929
TI  - A Novel Mutation in the ROGDI Gene in a Patient with Kohlschutter-Tonz Syndrome.
AB  - Kohlschutter-Tonz Syndrome (KTZS) is an autosomal recessive disorder caused by
      mutations in the ROGDI gene. This syndrome is characterized by epilepsy,
      psychomotor regression and amelogenesis imperfecta. In this paper, we report a
      case of a 13-year-old Malian girl presenting with this rare disease. By genetic
      analysis, we identified a novel ROGDI homozygous mutation NM_024589.1: c.117+1G>T
      [Chr16 (GRCh37): g.4852382C>A] which confirmed the diagnosis of Kohlschutter-Tonz
      syndrome. The mutation abolishes the usual splice donor site of intron 2 which
      leads to the deletion of exon 2 and in-frame assembly of exon 3. Exon 2 encodes a
      highly conserved leucine-rich region that is essential for ROGDI protein
      function. Hence, this deletion may affect the function of the ROGDI protein. 

PMID- 25565931
TI  - A plakophilin-1 gene mutation in an egyptian family with ectodermal dysplasia
      skin fragility syndrome.
AB  - Ectodermal dysplasia-skin fragility syndrome (ED-SFS) is a rare genodermatosis
      caused by mutations in the PKP1 gene, encoding the desmosomal plaque protein
      plakophilin-1. Since its initial description in 1997, few individuals with this
      disorder have been reported to date. Here, we present the first Egyptian cases of
      ED-SFS, carrying a novel homozygous mutation in the PKP1 gene. Direct sequencing
      of the amplified DNA from the affected cases disclosed a G-to-T transversion at
      nucleotide position c.203-1 within intron 1 of PKP1 (c.203-1G>T). To the best of
      our knowledge, this mutation has not been previously described in the databases. 

PMID- 25565930
TI  - Dihydropyrimidine dehydrogenase deficiency in two malaysian siblings with
      abnormal MRI findings.
AB  - Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive
      disorder of the pyrimidine metabolism. Deficiency of this enzyme leads to an
      accumulation of thymine and uracil and a deficiency of metabolites distal to the
      catabolic enzyme. The disorder presents with a wide clinical spectrum, ranging
      from asymptomatic to severe neurological manifestations, including intellectual
      disability, seizures, microcephaly, autistic behavior, and eye abnormalities.
      Here, we report on an 11-year-old Malaysian girl and her 6-year-old brother with
      DPD deficiency who presented with intellectual disability, microcephaly, and
      hypotonia. Brain MRI scans showed generalized cerebral and cerebellar atrophy and
      callosal body dysgenesis in the boy. Urine analysis showed strongly elevated
      levels of uracil in the girl and boy (571 and 578 mmol/mol creatinine,
      respectively) and thymine (425 and 427 mmol/mol creatinine, respectively).
      Sequence analysis of the DPYD gene showed that both siblings were homozygous for
      the mutation c.1651G>A (pAla551Thr). 

PMID- 25565932
TI  - Eosinophilic jejunitis presenting as intractable abdominal pain.
AB  - Eosinophilic gastroenteritis is an uncommon disease characterized by eosinophilic
      infiltration of the gastrointestinal tract. The clinical manifestations are
      related to the layer(s) and extent of the bowel involved. In this paper, we
      present a case of intractable abdominal pain caused by jejunal submucosal
      eosinophilic infiltration without mucosal involvement, diagnosed by deep
      endoscopic biopsies. The patient was successfully treated with steroids without
      need for surgery for diagnosis or therapy. 

PMID- 25565934
TI  - Successful Treatment of Septic Shock due to Spontaneous Esophageal Perforation 96
      Hours after Onset by Drainage and Enteral Nutrition.
AB  - Spontaneous esophageal perforation is relatively uncommon, but carries a high
      mortality rate if diagnosis or treatment is delayed. We report the case of a 68
      year-old man with spontaneous esophageal perforation who was successfully treated
      over 96 h after onset by thoracic drainage and jejunostomy for enteral nutrition.
      He vomited after drinking alcohol, soon followed by epigastralgia. Heart failure
      was suspected on admission to another hospital. Spontaneous esophageal
      perforation was diagnosed 48 h after admission. Chest tube drainage was
      performed, but his general condition deteriorated and he was transferred to our
      hospital. Emergent surgery was performed and esophageal perforation combined with
      pyothorax and mediastinitis was identified on the left side of the lower
      esophagus. The left thoracic cavity was rinsed and thoracic drainage was
      performed. Feeding jejunostomy was performed for postoperative enteral nutrition.
      Effective drainage and sufficient nutrition management appear extremely valuable
      in treating spontaneous esophageal perforation. 

PMID- 25565933
TI  - Gastrostomy Intraperitoneal Bumper Migration in a Three-Year-Old Child: A Rare
      Complication following Gastrostomy Tube Replacement.
AB  - Feeding gastrostomy is used worldwide for adults and children with feeding
      impairment to obtain long-term enteral nutrition. Percutaneous endoscopic
      gastrostomy insertion is considered the gold standard, but after the first months
      requires gastrostomy tube replacement with a low-profile button. The replacement
      is known as an easy procedure, but several minor and major complications may
      occur during and after the manoeuvre. We describe intraperitoneal bumper
      migration in a 3-year-old boy, a rare complication following gastrostomy tube
      replacement, and we discuss the recent literature regarding similar cases. 

PMID- 25565935
TI  - Prefrontal cortex hemodynamics and age: a pilot study using functional near
      infrared spectroscopy in children.
AB  - Cerebral hemodynamics reflect cognitive processes and underlying physiological
      processes, both of which are captured by functional near infrared spectroscopy
      (fNIRS). Here, we introduce a novel parameter of Oxygenation Variability directly
      obtained from fNIRS data -the OV Index-and we demonstrate its use in children.
      fNIRS data were collected from 17 children (ages 4-8 years), while they performed
      a standard Go/No-Go task. Data were analyzed using two frequency bands-the first
      attributed to cerebral autoregulation (CA) (<0.1 Hz) and the second to
      respiration (0.2-0.3 Hz). Results indicate differences in variability of
      oscillations of oxygen saturation (SO2) between the two different bands. These
      pilot data reveal a dynamic relationship between chronological age and OV index
      in CA associated frequency of <0.1 Hz. Specifically, OV index increased with age
      between 4 and 6 years. In addition, there was much higher variability in
      frequencies associated with CA than for respiration across subjects. These
      findings provide preliminary evidence for the utility of the OV index and are the
      first to describe the relationship between cerebral autoregulation and age in
      children using fNIRS methodology. 

PMID- 25565936
TI  - Heart rate variability: a tool to explore the sleeping brain?
AB  - Sleep is divided into two main sleep stages: (1) non-rapid eye movement sleep
      (non-REMS), characterized among others by reduced global brain activity; and (2)
      rapid eye movement sleep (REMS), characterized by global brain activity similar
      to that of wakefulness. Results of heart rate variability (HRV) analysis, which
      is widely used to explore autonomic modulation, have revealed higher
      parasympathetic tone during normal non-REMS and a shift toward sympathetic
      predominance during normal REMS. Moreover, HRV analysis combined with brain
      imaging has identified close connectivity between autonomic cardiac modulation
      and activity in brain areas such as the amygdala and insular cortex during REMS,
      but no connectivity between brain and cardiac activity during non-REMS. There is
      also some evidence for an association between HRV and dream intensity and
      emotionality. Following some technical considerations, this review addresses how
      brain activity during sleep contributes to changes in autonomic cardiac activity,
      organized into three parts: (1) the knowledge on autonomic cardiac control, (2)
      differences in brain and autonomic activity between non-REMS and REMS, and (3)
      the potential of HRV analysis to explore the sleeping brain, and the implications
      for psychiatric disorders. 

PMID- 25565937
TI  - Post-stroke balance rehabilitation under multi-level electrotherapy: a conceptual
      review.
AB  - Stroke is caused when an artery carrying blood from heart to an area in the brain
      bursts or a clot obstructs the blood flow thereby preventing delivery of oxygen
      and nutrients. About half of the stroke survivors are left with some degree of
      disability. Innovative methodologies for restorative neurorehabilitation are
      urgently required to reduce long-term disability. The ability of the nervous
      system to respond to intrinsic or extrinsic stimuli by reorganizing its
      structure, function, and connections is called neuroplasticity. Neuroplasticity
      is involved in post-stroke functional disturbances, but also in rehabilitation.
      It has been shown that active cortical participation in a closed-loop brain
      machine interface (BMI) can induce neuroplasticity in cortical networks where the
      brain acts as a controller, e.g., during a visuomotor task. Here, the motor task
      can be assisted with neuromuscular electrical stimulation (NMES) where the BMI
      will act as a real-time decoder. However, the cortical control and induction of
      neuroplasticity in a closed-loop BMI is also dependent on the state of brain,
      e.g., visuospatial attention during visuomotor task performance. In fact, spatial
      neglect is a hidden disability that is a common complication of stroke and is
      associated with prolonged hospital stays, accidents, falls, safety problems, and
      chronic functional disability. This hypothesis and theory article presents a
      multi-level electrotherapy paradigm toward motor rehabilitation in virtual
      reality that postulates that while the brain acts as a controller in a closed
      loop BMI to drive NMES, the state of brain can be can be altered toward
      improvement of visuomotor task performance with non-invasive brain stimulation
      (NIBS). This leads to a multi-level electrotherapy paradigm where a virtual
      reality-based adaptive response technology is proposed for post-stroke balance
      rehabilitation. In this article, we present a conceptual review of the related
      experimental findings. 

PMID- 25565939
TI  - Hierarchical organization of speech perception in human auditory cortex.
AB  - Human speech consists of a variety of articulated sounds that vary dynamically in
      spectral composition. We investigated the neural activity associated with the
      perception of two types of speech segments: (a) the period of rapid spectral
      transition occurring at the beginning of a stop-consonant vowel (CV) syllable and
      (b) the subsequent spectral steady-state period occurring during the vowel
      segment of the syllable. Functional magnetic resonance imaging (fMRI) was
      recorded while subjects listened to series of synthesized CV syllables and non
      phonemic control sounds. Adaptation to specific sound features was measured by
      varying either the transition or steady-state periods of the synthesized sounds.
      Two spatially distinct brain areas in the superior temporal cortex were found
      that were sensitive to either the type of adaptation or the type of stimulus. In
      a relatively large section of the bilateral dorsal superior temporal gyrus (STG),
      activity varied as a function of adaptation type regardless of whether the
      stimuli were phonemic or non-phonemic. Immediately adjacent to this region in a
      more limited area of the ventral STG, increased activity was observed for
      phonemic trials compared to non-phonemic trials, however, no adaptation effects
      were found. In addition, a third area in the bilateral medial superior temporal
      plane showed increased activity to non-phonemic compared to phonemic sounds. The
      results suggest a multi-stage hierarchical stream for speech sound processing
      extending ventrolaterally from the superior temporal plane to the superior
      temporal sulcus. At successive stages in this hierarchy, neurons code for
      increasingly more complex spectrotemporal features. At the same time, these
      representations become more abstracted from the original acoustic form of the
      sound. 

PMID- 25565940
TI  - Functional genomic analysis and neuroanatomical localization of miR-2954, a song
      responsive sex-linked microRNA in the zebra finch.
AB  - Natural experience can cause complex changes in gene expression in brain centers
      for cognition and perception, but the mechanisms that link perceptual experience
      and neurogenomic regulation are not understood. MicroRNAs (miRNAs or miRs) have
      the potential to regulate large gene expression networks, and a previous study
      showed that a natural perceptual stimulus (hearing the sound of birdsong in zebra
      finches) triggers rapid changes in expression of several miRs in the auditory
      forebrain. Here we evaluate the functional potential of one of these, miR-2954,
      which has been found so far only in birds and is encoded on the Z sex chromosome.
      Using fluorescence in situ hybridization and immunohistochemistry, we show that
      miR-2954 is present in subsets of cells in the sexually dimorphic brain regions
      involved in song production and perception, with notable enrichment in cell
      nuclei. We then probe its regulatory function by inhibiting its expression in a
      zebra finch cell line (G266) and measuring effects on endogenous gene expression
      using Illumina RNA sequencing (RNA-seq). Approximately 1000 different mRNAs
      change in expression by 1.5-fold or more (adjusted p < 0.01), with increases in
      some but not all of the targets that had been predicted by Targetscan. The
      population of RNAs that increase after miR-2954 inhibition is notably enriched
      for ones involved in the MAP Kinase (MAPK) pathway, whereas the decreasing
      population is dominated by genes involved in ribosomes and mitochondrial
      function. Since song stimulation itself triggers a decrease in miR-2954
      expression followed by a delayed decrease in genes encoding ribosomal and
      mitochondrial functions, we suggest that miR-2954 may mediate some of the
      neurogenomic effects of song habituation. 

PMID- 25565938
TI  - The rights and wrongs of blood-brain barrier permeability studies: a walk through
      100 years of history.
AB  - Careful examination of relevant literature shows that many of the most cherished
      concepts of the blood-brain barrier are incorrect. These include an almost
      mythological belief in its immaturity that is unfortunately often equated with
      absence or at least leakiness in the embryo and fetus. The original concept of a
      blood-brain barrier is often attributed to Ehrlich; however, he did not accept
      that permeability of cerebral vessels was different from other organs. Goldmann
      is often credited with the first experiments showing dye (trypan blue) exclusion
      from the brain when injected systemically, but not when injected directly into
      it. Rarely cited are earlier experiments of Bouffard and of Franke who showed
      methylene blue and trypan red stained all tissues except the brain. The term
      "blood-brain barrier" "Blut-Hirnschranke" is often attributed to Lewandowsky, but
      it does not appear in his papers. The first person to use this term seems to be
      Stern in the early 1920s. Studies in embryos by Stern and colleagues, Weed and
      Wislocki showed results similar to those in adult animals. These were well
      conducted experiments made a century ago, thus the persistence of a belief in
      barrier immaturity is puzzling. As discussed in this review, evidence for this
      belief, is of poor experimental quality, often misinterpreted and often not
      properly cited. The functional state of blood-brain barrier mechanisms in the
      fetus is an important biological phenomenon with implications for normal brain
      development. It is also important for clinicians to have proper evidence on which
      to advise pregnant women who may need to take medications for serious medical
      conditions. Beliefs in immaturity of the blood-brain barrier have held the field
      back for decades. Their history illustrates the importance of taking account of
      all the evidence and assessing its quality, rather than selecting papers that
      supports a preconceived notion or intuitive belief. This review attempts to right
      the wrongs. Based on careful translation of original papers, some published a
      century ago, as well as providing discussion of studies claiming to show barrier
      immaturity, we hope that readers will have evidence on which to base their own
      conclusions. 

PMID- 25565941
TI  - Brain fingerprinting classification concealed information test detects US Navy
      military medical information with P300.
AB  - A classification concealed information test (CIT) used the "brain fingerprinting"
      method of applying P300 event-related potential (ERP) in detecting information
      that is (1) acquired in real life and (2) unique to US Navy experts in military
      medicine. Military medicine experts and non-experts were asked to push buttons in
      response to three types of text stimuli. Targets contain known information
      relevant to military medicine, are identified to subjects as relevant, and
      require pushing one button. Subjects are told to push another button to all other
      stimuli. Probes contain concealed information relevant to military medicine, and
      are not identified to subjects. Irrelevants contain equally plausible, but
      incorrect/irrelevant information. Error rate was 0%. Median and mean statistical
      confidences for individual determinations were 99.9% with no indeterminates
      (results lacking sufficiently high statistical confidence to be classified). We
      compared error rate and statistical confidence for determinations of both
      information present and information absent produced by classification CIT (Is a
      probe ERP more similar to a target or to an irrelevant ERP?) vs. comparison CIT
      (Does a probe produce a larger ERP than an irrelevant?) using P300 plus the late
      negative component (LNP; together, P300-MERMER). Comparison CIT produced a
      significantly higher error rate (20%) and lower statistical confidences: mean
      67%; information-absent mean was 28.9%, less than chance (50%). We compared
      analysis using P300 alone with the P300 + LNP. P300 alone produced the same 0%
      error rate but significantly lower statistical confidences. These findings add to
      the evidence that the brain fingerprinting methods as described here provide
      sufficient conditions to produce less than 1% error rate and greater than 95%
      median statistical confidence in a CIT on information obtained in the course of
      real life that is characteristic of individuals with specific training,
      expertise, or organizational affiliation. 

PMID- 25565943
TI  - A compound memristive synapse model for statistical learning through STDP in
      spiking neural networks.
AB  - Memristors have recently emerged as promising circuit elements to mimic the
      function of biological synapses in neuromorphic computing. The fabrication of
      reliable nanoscale memristive synapses, that feature continuous conductance
      changes based on the timing of pre- and postsynaptic spikes, has however turned
      out to be challenging. In this article, we propose an alternative approach, the
      compound memristive synapse, that circumvents this problem by the use of
      memristors with binary memristive states. A compound memristive synapse employs
      multiple bistable memristors in parallel to jointly form one synapse, thereby
      providing a spectrum of synaptic efficacies. We investigate the computational
      implications of synaptic plasticity in the compound synapse by integrating the
      recently observed phenomenon of stochastic filament formation into an abstract
      model of stochastic switching. Using this abstract model, we first show how
      standard pulsing schemes give rise to spike-timing dependent plasticity (STDP)
      with a stabilizing weight dependence in compound synapses. In a next step, we
      study unsupervised learning with compound synapses in networks of spiking neurons
      organized in a winner-take-all architecture. Our theoretical analysis reveals
      that compound-synapse STDP implements generalized Expectation-Maximization in the
      spiking network. Specifically, the emergent synapse configuration represents the
      most salient features of the input distribution in a Mixture-of-Gaussians
      generative model. Furthermore, the network's spike response to spiking input
      streams approximates a well-defined Bayesian posterior distribution. We show in
      computer simulations how such networks learn to represent high-dimensional
      distributions over images of handwritten digits with high fidelity even in
      presence of substantial device variations and under severe noise conditions.
      Therefore, the compound memristive synapse may provide a synaptic design
      principle for future neuromorphic architectures. 

PMID- 25565945
TI  - An adaptive brain actuated system for augmenting rehabilitation.
AB  - For people living with paralysis, restoration of hand function remains the top
      priority because it leads to independence and improvement in quality of life. In
      approaches to restore hand and arm function, a goal is to better engage voluntary
      control and counteract maladaptive brain reorganization that results from non
      use. Standard rehabilitation augmented with developments from the study of brain
      computer interfaces could provide a combined therapy approach for motor cortex
      rehabilitation and to alleviate motor impairments. In this paper, an adaptive
      brain-computer interface system intended for application to control a functional
      electrical stimulation (FES) device is developed as an experimental test bed for
      augmenting rehabilitation with a brain-computer interface. The system's
      performance is improved throughout rehabilitation by passive user feedback and
      reinforcement learning. By continuously adapting to the user's brain activity,
      similar adaptive systems could be used to support clinical brain-computer
      interface neurorehabilitation over multiple days. 

PMID- 25565944
TI  - Barrier mechanisms in the Drosophila blood-brain barrier.
AB  - The invertebrate blood-brain barrier (BBB) field is growing at a rapid pace and,
      in recent years, studies have shown a physiologic and molecular complexity that
      has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular
      barrier maintenance through G-protein coupled receptor signaling were the first
      demonstrations of the complex adaptive mechanisms of barrier physiology. Building
      upon this work, the integrity of the invertebrate BBB has recently been shown to
      require coordinated function of all layers of the compound barrier structure,
      analogous to signaling between the layers of the vertebrate neurovascular unit.
      These findings strengthen the notion that many BBB mechanisms are conserved
      between vertebrates and invertebrates, and suggest that novel findings in
      invertebrate model organisms will have a significant impact on the understanding
      of vertebrate BBB functions. In this vein, important roles in coordinating
      localized and systemic signaling to dictate organism development and growth are
      beginning to show how the BBB can govern whole animal physiologies. This includes
      novel functions of BBB gap junctions in orchestrating synchronized neuroblast
      proliferation, and of BBB secreted antagonists of insulin receptor signaling.
      These advancements and others are pushing the field forward in exciting new
      directions. In this review, we provide a synopsis of invertebrate BBB anatomy and
      physiology, with a focus on insights from the past 5 years, and highlight
      important areas for future study. 

PMID- 25565942
TI  - Functional network alterations and their structural substrate in drug-resistant
      epilepsy.
AB  - The advent of MRI has revolutionized the evaluation and management of drug
      resistant epilepsy by allowing the detection of the lesion associated with the
      region that gives rise to seizures. Recent evidence indicates marked chronic
      alterations in the functional organization of lesional tissue and large-scale
      cortico-subcortical networks. In this review, we focus on recent methodological
      developments in functional MRI (fMRI) analysis techniques and their application
      to the two most common drug-resistant focal epilepsies, i.e., temporal lobe
      epilepsy related to mesial temporal sclerosis and extra-temporal lobe epilepsy
      related to focal cortical dysplasia. We put particular emphasis on methodological
      developments in the analysis of task-free or "resting-state" fMRI to probe the
      integrity of intrinsic networks on a regional, inter-regional, and connectome
      wide level. In temporal lobe epilepsy, these techniques have revealed disrupted
      connectivity of the ipsilateral mesiotemporal lobe, together with contralateral
      compensatory reorganization and striking reconfigurations of large-scale
      networks. In cortical dysplasia, initial observations indicate functional
      alterations in lesional, peri-lesional, and remote neocortical regions. While
      future research is needed to critically evaluate the reliability, sensitivity,
      and specificity, fMRI mapping promises to lend distinct biomarkers for diagnosis,
      presurgical planning, and outcome prediction. 

PMID- 25565947
TI  - Brain-machine interface to control a prosthetic arm with monkey ECoGs during
      periodic movements.
AB  - Brain-machine interfaces (BMIs) are promising technologies for rehabilitation of
      upper limb functions in patients with severe paralysis. We previously developed a
      BMI prosthetic arm for a monkey implanted with electrocorticography (ECoG)
      electrodes, and trained it in a reaching task. The stability of the BMI prevented
      incorrect movements due to misclassification of ECoG patterns. As a trade-off for
      the stability, however, the latency (the time gap between the monkey's actual
      motion and the prosthetic arm movement) was about 200 ms. Therefore, in this
      study, we aimed to improve the response time of the BMI prosthetic arm. We
      focused on the generation of a trigger event by decoding muscle activity in order
      to predict integrated electromyograms (iEMGs) from the ECoGs. We verified the
      achievability of our method by conducting a performance test of the proposed
      method with actual achieved iEMGs instead of predicted iEMGs. Our results
      confirmed that the proposed method with predicted iEMGs eliminated the time
      delay. In addition, we found that motor intention is better reflected by muscle
      activity estimated from brain activity rather than actual muscle activity.
      Therefore, we propose that using predicted iEMGs to guide prosthetic arm movement
      results in minimal delay and excellent performance. 

PMID- 25565946
TI  - Cytokine variations and mood disorders: influence of social stressors and social
      support.
AB  - Stressful events have been implicated in the evolution of mood disorders. In
      addition to brain neurotransmitters and growth factors, the view has been offered
      that these disorders might be provoked by the activation of the inflammatory
      immune system as well as by de novo changes of inflammatory cytokines within the
      brain. The present review describes the impact of social stressors in animals and
      in humans on behavioral changes reminiscent of depressive states as well as on
      cytokine functioning. Social stressors increase pro-inflammatory cytokines in
      circulation as well as in brain regions that have been associated with
      depression, varying with the animal's social status and/or behavioral methods
      used to contend with social challenges. Likewise, in humans, social stressors
      that favor the development of depression are accompanied by elevated circulating
      cytokine levels and conversely, conditions that limit the cytokine elevations
      correlated with symptom attenuation or reversal. The implications of these
      findings are discussed in relation to the potentially powerful effects of social
      support, social identity, and connectedness in maintaining well-being and in
      diminishing symptoms of depression. 

PMID- 25565948
TI  - Transcript co-variance with Nestin in two mouse genetic reference populations
      identifies Lef1 as a novel candidate regulator of neural precursor cell
      proliferation in the adult hippocampus.
AB  - Adult neurogenesis, the lifelong production of new neurons in the adult brain, is
      under complex genetic control but many of the genes involved remain to be
      identified. In this study, we have integrated publicly available gene expression
      data from the BXD and CXB recombinant inbred mouse lines to discover genes co
      expressed in the adult hippocampus with Nestin, a common marker of the neural
      precursor cell population. In addition, we incorporated spatial expression
      information to restrict candidates to genes with high differential gene
      expression in the hippocampal dentate gyrus. Incorporating data from curated
      protein-protein interaction databases revealed interactions between our candidate
      genes and those already known to be involved in adult neurogenesis. Enrichment
      analysis suggested a link to the Wnt/beta-catenin pathway, known to be involved
      in adult neurogenesis. In particular, our candidates were enriched in targets of
      Lef1, a modulator of the Wnt pathway. In conclusion, our combination of
      bioinformatics approaches identified six novel candidate genes involved in adult
      neurogenesis; Amer3, Eya3, Mtdh, Nr4a3, Polr2a, and Tbkbp1. Further, we propose a
      role for Lef1 transcriptional control in the regulation of adult hippocampal
      precursor cell proliferation. 

PMID- 25565949
TI  - Detection of abnormal resting-state networks in individual patients suffering
      from focal epilepsy: an initial step toward individual connectivity assessment.
AB  - The spatial coherence of spontaneous slow fluctuations in the blood-oxygen-level
      dependent (BOLD) signal at rest is routinely used to characterize the underlying
      resting-state networks (RSNs). Studies have demonstrated that these patterns are
      organized in space and highly reproducible from subject to subject. Moreover,
      RSNs reorganizations have been suggested in pathological conditions. Comparisons
      of RSNs organization have been performed between groups of subjects but have
      rarely been applied at the individual level, a step required for clinical
      application. Defining the notion of modularity as the organization of brain
      activity in stable networks, we propose Detection of Abnormal Networks in
      Individuals (DANI) to identify modularity changes at the individual level. The
      stability of each RSN was estimated using a spatial clustering method: Bootstrap
      Analysis of Stable Clusters (BASC) (Bellec et al., 2010). Our contributions
      consisted in (i) providing functional maps of the most stable cores of each
      networks and (ii) in detecting "abnormal" individual changes in networks
      organization when compared to a population of healthy controls. DANI was first
      evaluated using realistic simulated data, showing that focussing on a
      conservative core size (50% most stable regions) improved the sensitivity to
      detect modularity changes. DANI was then applied to resting state fMRI data of
      six patients with focal epilepsy who underwent multimodal assessment using
      simultaneous EEG/fMRI acquisition followed by surgery. Only patient with a
      seizure free outcome were selected and the resected area was identified using a
      post-operative MRI. DANI automatically detected abnormal changes in 5 out of 6
      patients, with excellent sensitivity, showing for each of them at least one
      "abnormal" lateralized network closely related to the epileptic focus. For each
      patient, we also detected some distant networks as abnormal, suggesting some
      remote reorganization in the epileptic brain. 

PMID- 25565950
TI  - Identification of neural cells activated by mating stimulus in the periaqueductal
      gray in female rats.
AB  - Induction of lordosis as typical female sexual behavior in rodents is dependent
      on a mount stimulus from males and blood levels of estrogen. Periaqueductal gray
      (PAG) efferent neurons have been suggested to be important for lordosis behavior;
      however, the neurochemical basis remains to be understood. In this study, we
      neuroanatomically examined (1) whether PAG neurons activated by mating stimulus
      project to the medullary reticular formation (MRF), which is also a required area
      for lordosis; and (2) whether these neurons are glutamatergic. Mating stimulus
      significantly increased the number of cFos-immunoreactive (ir) neurons in the
      PAG, particularly in its lateral region. Half of cFos-ir neurons in the lateral
      PAG were positive for a retrograde tracer (FluoroGold; FG) injected into the MRF.
      cFos-ir neurons also colocalized with mRNA of vesicular glutamate transporter 2
      (vGLUT2), a molecular marker for glutamatergic neurons. Using retrograde tracing
      and in situ hybridization in conjunction with fluorescent microscopy, we also
      found FG and vGLUT2 mRNA double-positive neurons in the lateral PAG. These
      results suggest that glutamatergic neurons in the lateral PAG project to the MRF
      and are involved in lordosis behavior in female rats. 

PMID- 25565952
TI  - Research topic: neuromorphic engineering systems and applications. A snapshot of
      neuromorphic systems engineering.

PMID- 25565951
TI  - Single-subject analyses of magnetoencephalographic evoked responses to the
      acoustic properties of affective non-verbal vocalizations.
AB  - Magneto-encephalography (MEG) was used to examine the cerebral response to
      affective non-verbal vocalizations (ANVs) at the single-subject level. Stimuli
      consisted of non-verbal affect bursts from the Montreal Affective Voices morphed
      to parametrically vary acoustical structure and perceived emotional properties.
      Scalp magnetic fields were recorded in three participants while they performed a
      3-alternative forced choice emotion categorization task (Anger, Fear, Pleasure).
      Each participant performed more than 6000 trials to allow single-subject level
      statistical analyses using a new toolbox which implements the general linear
      model (GLM) on stimulus-specific responses (LIMO-EEG). For each participant we
      estimated "simple" models [including just one affective regressor (Arousal or
      Valence)] as well as "combined" models (including acoustical regressors). Results
      from the "simple" models revealed in every participant the significant early
      effects (as early as ~100 ms after onset) of Valence and Arousal already reported
      at the group-level in previous work. However, the "combined" models showed that
      few effects of Arousal remained after removing the acoustically-explained
      variance, whereas significant effects of Valence remained especially at late
      stages. This study demonstrates (i) that single-subject analyses replicate the
      results observed at early stages by group-level studies and (ii) the feasibility
      of GLM-based analysis of MEG data. It also suggests that early modulation of MEG
      amplitude by affective stimuli partly reflects their acoustical properties. 

PMID- 25565953
TI  - Sex-specific strategy use and global-local processing: a perspective toward
      integrating sex differences in cognition.
AB  - This article reviews the literature on sex-specific strategy use in cognitive
      tasks with the aim to carve out a link between sex differences in different
      cognitive tasks. I conclude that male strategies are commonly holistic and
      oriented toward global stimulus aspects, while female strategies are commonly
      decomposed and oriented toward local stimulus aspects. Thus, the strategies
      observed in different tasks, may depend on sex differences in attentional focus
      and hence sex differences in global-local processing. I hypothesize that strategy
      use may be sex hormone dependent and hence subject to change over the menstrual
      cycle as evidenced by findings in global-local processing and emotional memory.
      Furthermore, I propose sex hormonal modulation of hemispheric asymmetries as one
      possible neural substrate for this theory, thereby building on older theories,
      emphasizing the importance of sex differences in brain lateralization. The ideas
      described in the current article represent a perspective toward a unifying
      approach to the study of sex differences in cognition and their neural
      correlates. 

PMID- 25565954
TI  - Synaptic adaptations by alcohol and drugs of abuse: changes in microRNA
      expression and mRNA regulation.
AB  - Local translation of mRNAs is a mechanism by which cells can rapidly remodel
      synaptic structure and function. There is ample evidence for a role of synaptic
      translation in the neuroadaptations resulting from chronic drug use and abuse.
      Persistent and coordinated changes of many mRNAs, globally and locally, may have
      a causal role in complex disorders such as addiction. In this review we examine
      the evidence that translational regulation by microRNAs drives synaptic
      remodeling and mRNA expression, which may regulate the transition from
      recreational to compulsive drug use. microRNAs are small, non-coding RNAs that
      control the translation of mRNAs in the cell and within spatially restricted
      sites such as the synapse. microRNAs typically repress the translation of mRNAs
      into protein by binding to the 3'UTR of their targets. As 'master regulators' of
      many mRNAs, changes in microRNAs could account for the systemic alterations in
      mRNA and protein expression observed with drug abuse and dependence. Recent
      studies indicate that manipulation of microRNAs affects addiction-related
      behaviors such as the rewarding properties of cocaine, cocaine-seeking behavior,
      and self-administration rates of alcohol. There is limited evidence, however,
      regarding how synaptic microRNAs control local mRNA translation during chronic
      drug exposure and how this contributes to the development of dependence. Here, we
      discuss research supporting microRNA regulation of local mRNA translation and how
      drugs of abuse may target this process. The ability of synaptic microRNAs to
      rapidly regulate mRNAs provides a discrete, localized system that could
      potentially be used as diagnostic and treatment tools for alcohol and other
      addiction disorders. 

PMID- 25565957
TI  - HMG-CoA Reductase Inhibition Promotes Neurological Recovery, Peri-Lesional Tissue
      Remodeling, and Contralesional Pyramidal Tract Plasticity after Focal Cerebral
      Ischemia.
AB  - 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are widely
      used for secondary stroke prevention. Besides their lipid-lowering activity,
      pleiotropic effects on neuronal survival, angiogenesis, and neurogenesis have
      been described. In view of these observations, we were interested whether HMG-CoA
      reductase inhibition in the post-acute stroke phase promotes neurological
      recovery, peri-lesional, and contralesional neuronal plasticity. We examined
      effects of the HMG-CoA reductase inhibitor rosuvastatin (0.2 or 2.0 mg/kg/day
      i.c.v.), administered starting 3 days after 30 min of middle cerebral artery
      occlusion for 30 days. Here, we show that rosuvastatin treatment significantly
      increased the grip strength and motor coordination of animals, promoted
      exploration behavior, and reduced anxiety. It was associated with structural
      remodeling of peri-lesional brain tissue, reflected by increased neuronal
      survival, enhanced capillary density, and reduced striatal and corpus callosum
      atrophy. Increased sprouting of contralesional pyramidal tract fibers crossing
      the midline in order to innervate the ipsilesional red nucleus was noticed in
      rosuvastatin compared with vehicle-treated mice, as shown by anterograde tract
      tracing experiments. Western blot analysis revealed that the abundance of HMG-CoA
      reductase was increased in the contralesional hemisphere at 14 and 28 days post
      ischemia. Our data support the idea that HMG-CoA reductase inhibition promotes
      brain remodeling and plasticity far beyond the acute stroke phase, resulting in
      neurological recovery. 

PMID- 25565955
TI  - The dendritic SNARE fusion machinery involved in AMPARs insertion during long
      term potentiation.
AB  - Sorting endosomes carry alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA)-type glutamate receptors (AMPARs) from their maturation sites to their
      final destination at the dendritic plasma membrane through both constitutive and
      regulated exocytosis. Insertion of functional AMPARs into the postsynaptic
      membrane is essential for maintaining fast excitatory synaptic transmission and
      plasticity. Despite this crucial role in neuronal function, the machinery
      mediating the fusion of AMPAR-containing endosomes in dendrites has been largely
      understudied in comparison to presynaptic vesicle exocytosis. Increasing evidence
      suggests that similarly to neurotransmitter release, AMPARs insertion relies on
      the formation of a SNARE complex (soluble NSF-attachment protein receptor), whose
      composition in dendrites has just begun to be elucidated. This review analyzes
      recent findings of the fusion machinery involved in regulated AMPARs insertion
      and discusses how dendritic exocytosis and AMPARs lateral diffusion may work
      together to support synaptic plasticity. 

PMID- 25565956
TI  - Gliomas and the vascular fragility of the blood brain barrier.
AB  - Astrocytes, members of the glial family, interact through the exchange of soluble
      factors or by directly contacting neurons and other brain cells, such as
      microglia and endothelial cells. Astrocytic projections interact with vessels and
      act as additional elements of the Blood Brain Barrier (BBB). By mechanisms not
      fully understood, astrocytes can undergo oncogenic transformation and give rise
      to gliomas. The tumors take advantage of the BBB to ensure survival and
      continuous growth. A glioma can develop into a very aggressive tumor, the
      glioblastoma (GBM), characterized by a highly heterogeneous cell population
      (including tumor stem cells), extensive proliferation and migration.
      Nevertheless, gliomas can also give rise to slow growing tumors and in both
      cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different
      regions of the brain guided by the extension of blood vessels, colonizing the
      healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived
      seizures, which represent a challenge to patients and clinicians, since drugs
      used for its treatment must be able to cross the BBB. Uncontrolled and fast
      growth also leads to the disruption of the chimeric and fragile vessels in the
      tumor mass resulting in peritumoral edema. Although hormonal therapy is currently
      used to control the edema, it is not always efficient. In this review we comment
      the points cited above, considering the importance of the BBB and the concerns
      that arise when this barrier is affected. 

PMID- 25565959
TI  - The heterogeneity in GABAA receptor-mediated IPSC kinetics reflects heterogeneity
      of subunit composition among inhibitory and excitatory interneurons in spinal
      lamina II.
AB  - GABAergic inhibition displays rich functional diversity throughout the CNS, which
      arises from variations in the nature of inputs, subunit composition, subcellular
      localization of receptors and synapse geometry, or reuptake mechanisms. In the
      spinal dorsal horn (SDH), GABAA and glycine receptors play a major role in the
      control of excitability and accuracy of nociceptive processing. Identifying which
      components shape the properties of the inhibitory synapses in different cell
      types is necessary to understand how nociceptive information is integrated. To
      address this, we used transgenic mice where inhibitory interneurons express GAD65
      EGFP. We found that GABAA, but not glycine receptor-mediated evoked IPSCs
      displayed slower kinetics in EGFP+ vs. EGFP- interneurons. GABAA miniature IPSC
      decay kinetics showed a large variability in both populations, however the
      distribution of decays differed between EGFP+ and EGFP- interneurons. The range
      of mIPSC decay kinetics observed was replicated in experiments using rapid
      application of GABA on outside-out patches taken from SDH neurons in slices.
      Furthermore, GABAA decay kinetics were not affected by uptake blockers and were
      not different in mice lacking delta or alpha5 subunits, indicating that intrinsic
      channel properties likely underlie the heterogeneity. To identify whether other
      alpha subunits shape the various kinetic properties observed we took advantage of
      knock-in mice carrying point mutations in either the alpha1, alpha2, or alpha3
      subunits rendering Ro 15-4513 a selective agonist at the benzodiazepine
      modulatory site. We found that alpha1 and alpha2 subunit underlie the fast
      decaying component of IPSCs while the slow component is determined by the alpha3
      subunit. The differential distribution of GABAA subunits at inhibitory synapses
      thus sculpts the heterogeneity of the SDH inhibitory circuitry. This diversity of
      inhibitory elements can be harnessed to selectively modulate different components
      of the spinal nociceptive circuitry for therapeutic interventions. 

PMID- 25565958
TI  - Learning modulation of odor representations: new findings from Arc-indexed
      networks.
AB  - We first review our understanding of odor representations in rodent olfactory
      bulb (OB) and anterior piriform cortex (APC). We then consider learning-induced
      representation changes. Finally we describe the perspective on network
      representations gained from examining Arc-indexed odor networks of awake rats.
      Arc-indexed networks are sparse and distributed, consistent with current views.
      However Arc provides representations of repeated odors. Arc-indexed repeated odor
      representations are quite variable. Sparse representations are assumed to be
      compact and reliable memory codes. Arc suggests this is not necessarily the case.
      The variability seen is consistent with electrophysiology in awake animals and
      may reflect top-down cortical modulation of context. Arc-indexing shows that
      distinct odors share larger than predicted neuron pools. These may be low
      threshold neuronal subsets. Learning's effect on Arc-indexed representations is
      to increase the stable or overlapping component of rewarded odor representations.
      This component can decrease for similar odors when their discrimination is
      rewarded. The learning effects seen are supported by electrophysiology, but
      mechanisms remain to be elucidated. 

PMID- 25565960
TI  - Functional changes in glutamate transporters and astrocyte biophysical properties
      in a rodent model of focal cortical dysplasia.
AB  - Cortical dysplasia is associated with intractable epilepsy and developmental
      delay in young children. Recent work with the rat freeze-induced focal cortical
      dysplasia (FCD) model has demonstrated that hyperexcitability in the dysplastic
      cortex is due in part to higher levels of extracellular glutamate. Astrocyte
      glutamate transporters play a pivotal role in cortical maintaining extracellular
      glutamate concentrations. Here we examined the function of astrocytic glutamate
      transporters in a FCD model in rats. Neocortical freeze lesions were made in
      postnatal day (PN) 1 rat pups and whole cell electrophysiological recordings and
      biochemical studies were performed at PN 21-28. Synaptically evoked glutamate
      transporter currents in astrocytes showed a near 10-fold reduction in amplitude
      compared to sham operated controls. Astrocyte glutamate transporter currents from
      lesioned animals were also significantly reduced when challenged exogenously
      applied glutamate. Reduced astrocytic glutamate transport clearance contributed
      to increased NMDA receptor-mediated current decay kinetics in lesioned animals.
      The electrophysiological profile of astrocytes in the lesion group was also
      markedly changed compared to sham operated animals. Control astrocytes
      demonstrate large-amplitude linear leak currents in response to voltage-steps
      whereas astrocytes in lesioned animals demonstrated significantly smaller voltage
      activated inward and outward currents. Significant decreases in astrocyte resting
      membrane potential and increases in input resistance were observed in lesioned
      animals. However, Western blotting, immunohistochemistry and quantitative PCR
      demonstrated no differences in the expression of the astrocytic glutamate
      transporter GLT-1 in lesioned animals relative to controls. These data suggest
      that, in the absence of changes in protein or mRNA expression levels, functional
      changes in astrocytic glutamate transporters contribute to neuronal
      hyperexcitability in the FCD model. 

PMID- 25565962
TI  - Glutamic acid decarboxylase 67 expression by a distinct population of mouse
      vestibular supporting cells.
AB  - The function of the enzyme glutamate decarboxylase (GAD) is to convert glutamate
      in gamma-aminobutyric acid (GABA). Glutamate decarboxylase exists as two major
      isoforms, termed GAD65 and GAD67, that are usually expressed in GABA-containing
      neurons in the central nervous system. GAD65 has been proposed to be associated
      with GABA exocytosis whereas GAD67 with GABA metabolism. In the present
      immunofluorescence study, we have investigated the presence of the two GAD
      isoforms in the semicircular canal cristae of wild type and GAD67-GFP knock-in
      mice. While no evidence for GAD65 expression was found, GAD67 was detected in a
      distinct population of peripherally-located supporting cells, but not in hair
      cells or in centrally-located supporting cells. GABA, on the other hand, was
      found in all supporting cells. The present result indicate that only a discrete
      population of supporting cells use GAD67 to synthesize GABA. This is the first
      report of a marker that allows to distinguish two populations of supporting cells
      in the vestibular epithelium. On the other hand, the lack of GABA and GAD enzymes
      in hair cells excludes its involvement in afferent transmission. 

PMID- 25565961
TI  - The gamma-secretase complex: from structure to function.
AB  - One of the most critical pathological features of Alzheimer's disease (AD) is the
      accumulation of beta-amyloid (Abeta) peptides that form extracellular senile
      plaques in the brain. Abeta is derived from beta-amyloid precursor protein (APP)
      through sequential cleavage by beta- and gamma-secretases. gamma-secretase is a
      high molecular weight complex minimally composed of four components: presenilins
      (PS), nicastrin, anterior pharynx defective 1 (APH-1), and presenilin enhancer 2
      (PEN-2). In addition to APP, gamma-secretase also cleaves many other type I
      transmembrane (TM) protein substrates. As a crucial enzyme for Abeta production,
      gamma-secretase is an appealing therapeutic target for AD. Here, we summarize
      current knowledge on the structure and function of gamma-secretase, as well as
      recent progress in developing gamma-secretase targeting drugs for AD treatment. 

PMID- 25565964
TI  - Brain-derived neurotrophic factor: a bridge between inflammation and
      neuroplasticity.
AB  - Cytokines are key regulatory mediators involved in the host response to
      immunological challenges, but also play a critical role in the communication
      between the immune and the central nervous system. For this, their expression in
      both systems is under a tight regulatory control. However, pathological
      conditions may lead to an overproduction of pro-inflammatory cytokines that may
      have a detrimental impact on central nervous system. In particular, they may
      damage neuronal structure and function leading to deficits of neuroplasticity,
      the ability of nervous system to perceive, respond and adapt to external or
      internal stimuli. In search of the mechanisms by which pro-inflammatory cytokines
      may affect this crucial brain capability, we will discuss one of the most
      interesting hypotheses: the involvement of the neurotrophin brain-derived
      neurotrophic factor (BDNF), which represents one of the major mediators of
      neuroplasticity. 

PMID- 25565963
TI  - Diffuse axonal injury in brain trauma: insights from alterations in
      neurofilaments.
AB  - Traumatic brain injury (TBI) from penetrating or closed forces to the cranium can
      result in a range of forms of neural damage, which culminate in mortality or
      impart mild to significant neurological disability. In this regard, diffuse
      axonal injury (DAI) is a major neuronal pathophenotype of TBI and is associated
      with a complex set of cytoskeletal changes. The neurofilament triplet proteins
      are key structural cytoskeletal elements, which may also be important
      contributors to the tensile strength of axons. This has significant implications
      with respect to how axons may respond to TBI. It is not known, however, whether
      neurofilament compaction and the cytoskeletal changes that evolve following
      axonal injury represent a component of a protective mechanism following damage,
      or whether they serve to augment degeneration and progression to secondary
      axotomy. Here we review the structure and role of neurofilament proteins in
      normal neuronal function. We also discuss the processes that characterize DAI and
      the resultant alterations in neurofilaments, highlighting potential clues to a
      possible protective or degenerative influence of specific neurofilament
      alterations within injured neurons. The potential utility of neurofilament assays
      as biomarkers for axonal injury is also discussed. Insights into the complex
      alterations in neurofilaments will contribute to future efforts in developing
      therapeutic strategies to prevent, ameliorate or reverse neuronal degeneration in
      the central nervous system (CNS) following traumatic injury. 

PMID- 25565965
TI  - RNA-mediated pathogenic mechanisms in polyglutamine diseases and amyotrophic
      lateral sclerosis.
AB  - Gene transcription produces a wide variety of ribonucleic acid (RNA) species in
      eukaryotes. Individual types of RNA, such as messenger, structural and regulatory
      RNA, are known to play distinct roles in the cell. Recently, researchers have
      identified a large number of RNA-mediated toxicity pathways that play significant
      pathogenic roles in numerous human disorders. In this article, we describe
      various common RNA toxicity pathways, namely epigenetic gene silencing, nucleolar
      stress, nucleocytoplasmic transport, bi-directional gene transcription, repeat
      associated non-ATG translation, RNA foci formation and cellular protein
      sequestration. We emphasize RNA toxicity mechanisms that involve nucleotide
      repeat expansion, such as those related to polyglutamine (polyQ) disorders and
      frontotemporal lobar degeneration-amyotrophic lateral sclerosis. 

PMID- 25565966
TI  - GNX-4728, a novel small molecule drug inhibitor of mitochondrial permeability
      transition, is therapeutic in a mouse model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder in humans
      characterized by progressive degeneration of skeletal muscle and motor neurons in
      spinal cord, brainstem, and cerebral cortex causing skeletal muscle paralysis,
      respiratory insufficiency, and death. There are no cures or effective treatments
      for ALS. ALS can be inherited, but most cases are not associated with a family
      history of the disease. Mitochondria have been implicated in the pathogenesis but
      definitive proof of causal mechanisms is lacking. Identification of new
      clinically translatable disease mechanism-based molecular targets and small
      molecule drug candidates are needed for ALS patients. We tested the hypothesis in
      an animal model that drug modulation of the mitochondrial permeability transition
      pore (mPTP) is therapeutic in ALS. A prospective randomized placebo-controlled
      drug trial was done in a transgenic (tg) mouse model of ALS. We explored GNX-4728
      as a therapeutic drug. GNX-4728 inhibits mPTP opening as evidenced by increased
      mitochondrial calcium retention capacity (CRC) both in vitro and in vivo. Chronic
      systemic treatment of G37R-human mutant superoxide dismutase-1 (hSOD1) tg mice
      with GNX-4728 resulted in major therapeutic benefits. GNX-4728 slowed disease
      progression and significantly improved motor function. The survival of ALS mice
      was increased significantly by GNX-4728 treatment as evidence by a nearly 2-fold
      extension of lifespan (360 days-750 days). GNX-4728 protected against motor
      neuron degeneration and mitochondrial degeneration, attenuated spinal cord
      inflammation, and preserved neuromuscular junction (NMJ) innervation in the
      diaphragm in ALS mice. This work demonstrates that a mPTP-acting drug has major
      disease-modifying efficacy in a preclinical mouse model of ALS and establishes
      mitochondrial calcium retention, and indirectly the mPTP, as targets for ALS drug
      development. 

PMID- 25565967
TI  - Subventricular zone progenitors in time and space: generating neuronal diversity.
AB  - The adult mammalian brain harbors a population of cells around their lateral
      ventricles capable of giving rise to new neurons throughout life. The so-called
      subventricular zone (SVZ) is a heterogeneous germinative niche in regard to the
      neuronal types it generates. SVZ progenitors give rise to different olfactory
      bulb (OB) interneuron types in accordance to their position along the ventricles.
      Here, I review data showing the difference between progenitors located along
      different parts of the SVZ axes and ages. I also discuss possible mechanisms for
      the origin of this diversity. 

PMID- 25565968
TI  - Augmented Inhibition from Cannabinoid-Sensitive Interneurons Diminishes CA1
      Output after Traumatic Brain Injury.
AB  - The neurological impairments associated with traumatic brain injury include
      learning and memory deficits and increased risk of seizures. The hippocampus is
      critically involved in both of these phenomena and highly susceptible to damage
      by traumatic brain injury. To examine network activity in the hippocampal CA1
      region after lateral fluid percussion injury, we used a combination of voltage
      sensitive dye, field potential, and patch clamp recording in mouse hippocampal
      brain slices. When the stratum radiatum (SR) was stimulated in slices from
      injured mice, we found decreased depolarization in SR and increased
      hyperpolarization in stratum oriens (SO), together with a decrease in the
      percentage of pyramidal neurons firing stimulus-evoked action potentials.
      Increased hyperpolarization in SO persisted when glutamatergic transmission was
      blocked. However, we found no changes in SO responses when the alveus was
      stimulated to directly activate SO. These results suggest that the increased SO
      hyperpolarization evoked by SR stimulation was mediated by interneurons that have
      cell bodies and/or axons in SR, and form synapses in stratum pyramidale and SO. A
      low concentration (100 nM) of the synthetic cannabinoid WIN55,212-2, restored CA1
      output in slices from injured animals. These findings support the hypothesis that
      increased GABAergic signaling by cannabinoid-sensitive interneurons contributes
      to the reduced CA1 output following traumatic brain injury. 

PMID- 25565969
TI  - Gene regulatory network analysis reveals differences in site-specific cell fate
      determination in mammalian brain.
AB  - Neurogenesis-the generation of new neurons-is an ongoing process that persists in
      the adult mammalian brain of several species, including humans. In this work we
      analyze two discrete brain regions: the subventricular zone (SVZ) lining the
      walls of the lateral ventricles; and the subgranular zone (SGZ) of the dentate
      gyrus (DG) of the hippocampus in mice and shed light on the SVZ and SGZ specific
      neurogenesis. We propose a computational model that relies on the construction
      and analysis of region specific gene regulatory networks (GRNs) from the publicly
      available data on these two regions. Using this model a number of putative
      factors involved in neuronal stem cell (NSC) identity and maintenance were
      identified. We also demonstrate potential gender and niche-derived differences
      based on cell surface and nuclear receptors via Ar, Hif1a, and Nr3c1. We have
      also conducted cell fate determinant analysis for SVZ NSC populations to
      Olfactory Bulb interneurons and SGZ NSC populations to the granule cells of the
      Granular Cell Layer. We report 31 candidate cell fate determinant gene pairs,
      ready to be validated. We focus on Ar-Pax6 in SVZ and Sox2-Ncor1 in SGZ. Both
      pairs are expressed and localized in the suggested anatomical structures as shown
      by in situ hybridization and found to physically interact. Finally, we conclude
      that there are fundamental differences between SGZ and SVZ neurogenesis. We argue
      that these regulatory mechanisms are linked to the observed differential
      neurogenic potential of these regions. The presence of nuclear and cell surface
      receptors in the region specific regulatory circuits indicate the significance of
      niche derived extracellular factors, hormones and region specific factors such as
      the oxygen sensitivity, dictating SGZ and SVZ specific neurogenesis. 

PMID- 25565970
TI  - GABA as a rising gliotransmitter.
AB  - Gamma-amino butyric acid (GABA) is the major inhibitory neurotransmitter that is
      known to be synthesized and released from GABAergic neurons in the brain.
      However, recent studies have shown that not only neurons but also astrocytes
      contain a considerable amount of GABA that can be released and activate GABA
      receptors in neighboring neurons. These exciting new findings for glial GABA
      raise further interesting questions about the source of GABA, its mechanism of
      release and regulation and the functional role of glial GABA. In this review, we
      highlight recent studies that identify the presence and release of GABA in glial
      cells, we show several proposed potential pathways for accumulation and
      modulation of glial intracellular and extracellular GABA content, and finally we
      discuss functional roles for glial GABA in the brain. 

PMID- 25565971
TI  - Linear coding of complex sound spectra by discharge rate in neurons of the medial
      nucleus of the trapezoid body (MNTB) and its inputs.
AB  - The interaural level difference (ILD) cue to sound location is first encoded in
      the lateral superior olive (LSO). ILD sensitivity results because the LSO
      receives excitatory input from the ipsilateral cochlear nucleus and inhibitory
      input indirectly from the contralateral cochlear nucleus via glycinergic neurons
      of the ipsilateral medial nucleus of the trapezoid body (MNTB). It is
      hypothesized that in order for LSO neurons to encode ILDs, the sound spectra at
      both ears must be accurately encoded via spike rate by their afferents. This
      spectral-coding hypothesis has not been directly tested in MNTB, likely because
      MNTB neurons have been mostly described and studied recently in regards to their
      abilities to encode temporal aspects of sounds, not spectral. Here, we test the
      hypothesis that MNTB neurons and their inputs from the cochlear nucleus and
      auditory nerve code sound spectra via discharge rate. The Random Spectral Shape
      (RSS) method was used to estimate how the levels of 100-ms duration spectrally
      stationary stimuli were weighted, both linearly and non-linearly, across a wide
      band of frequencies. In general, MNTB neurons, and their globular bushy cell
      inputs, were found to be well-modeled by a linear weighting of spectra
      demonstrating that the pathways through the MNTB can accurately encode sound
      spectra including those resulting from the acoustical cues to sound location
      provided by head-related directional transfer functions (DTFs). Together with the
      anatomical and biophysical specializations for timing in the MNTB-LSO complex,
      these mechanisms may allow ILDs to be computed for complex stimuli with rapid
      spectrotemporally-modulated envelopes such as speech and animal vocalizations and
      moving sound sources. 

PMID- 25565972
TI  - Activity-dependent modulation of inhibitory synaptic kinetics in the cochlear
      nucleus.
AB  - Spherical bushy cells (SBCs) in the anteroventral cochlear nucleus respond to
      acoustic stimulation with discharges that precisely encode the phase of low
      frequency sound. The accuracy of spiking is crucial for sound localization and
      speech perception. Compared to the auditory nerve input, temporal precision of
      SBC spiking is improved through the engagement of acoustically evoked inhibition.
      Recently, the inhibition was shown to be less precise than previously understood.
      It shifts from predominantly glycinergic to synergistic GABA/glycine transmission
      in an activity-dependent manner. Concurrently, the inhibition attains a tonic
      character through temporal summation. The present study provides a comprehensive
      understanding of the mechanisms underlying this slow inhibitory input. We
      performed whole-cell voltage clamp recordings on SBCs from juvenile Mongolian
      gerbils and recorded evoked inhibitory postsynaptic currents (IPSCs) at
      physiological rates. The data reveal activity-dependent IPSC kinetics, i.e., the
      decay is slowed with increased input rates or recruitment. Lowering the release
      probability yielded faster decay kinetics of the single- and short train-IPSCs at
      100 Hz, suggesting that transmitter quantity plays an important role in
      controlling the decay. Slow transmitter clearance from the synaptic cleft caused
      prolonged receptor binding and, in the case of glycine, spillover to nearby
      synapses. The GABAergic component prolonged the decay by contributing to the
      asynchronous vesicle release depending on the input rate. Hence, the different
      factors controlling the amount of transmitters in the synapse jointly slow the
      inhibition during physiologically relevant activity. Taken together, the slow
      time course is predominantly determined by the receptor kinetics and transmitter
      clearance during short stimuli, whereas long duration or high frequency
      stimulation additionally engage asynchronous release to prolong IPSCs. 

PMID- 25565973
TI  - Rapid development of Purkinje cell excitability, functional cerebellar circuit,
      and afferent sensory input to cerebellum in zebrafish.
AB  - The zebrafish has significant advantages for studying the morphological
      development of the brain. However, little is known about the functional
      development of the zebrafish brain. We used patch clamp electrophysiology in live
      animals to investigate the emergence of excitability in cerebellar Purkinje
      cells, functional maturation of the cerebellar circuit, and establishment of
      sensory input to the cerebellum. Purkinje cells are born at 3 days post
      fertilization (dpf). By 4 dpf, Purkinje cells spontaneously fired action
      potentials in an irregular pattern. By 5 dpf, the frequency and regularity of
      tonic firing had increased significantly and most cells fired complex spikes in
      response to climbing fiber activation. Our data suggest that, as in mammals,
      Purkinje cells are initially innervated by multiple climbing fibers that are
      winnowed to a single input. To probe the development of functional sensory input
      to the cerebellum, we investigated the response of Purkinje cells to a visual
      stimulus consisting of a rapid change in light intensity. At 4 dpf, sudden
      darkness increased the rate of tonic firing, suggesting that afferent pathways
      carrying visual information are already active by this stage. By 5 dpf, visual
      stimuli also activated climbing fibers, increasing the frequency of complex
      spiking. Our results indicate that the electrical properties of zebrafish and
      mammalian Purkinje cells are highly conserved and suggest that the same ion
      channels, Nav1.6 and Kv3.3, underlie spontaneous pacemaking activity.
      Interestingly, functional development of the cerebellum is temporally correlated
      with the emergence of complex, visually-guided behaviors such as prey capture.
      Because of the rapid formation of an electrically-active cerebellum, optical
      transparency, and ease of genetic manipulation, the zebrafish has great potential
      for functionally mapping cerebellar afferent and efferent pathways and for
      investigating cerebellar control of motor behavior. 

PMID- 25565974
TI  - Neurochemical phenotype and function of endomorphin 2-immunopositive neurons in
      the myenteric plexus of the rat colon.
AB  - The distribution and activity of endomorphins (EMs), which are endogenous MU
      opioid receptor (MOR) ligands in the gastrointestinal tract (GI), are yet to be
      elucidated. The current study aimed to shed light on this topic. EM2 was
      expressed in the enteric neurons in the myenteric plexus of the mid-colon. Of the
      EM2-immunoreactive (EM2-IR) neurons, 53 +/- 4.6%, 26 +/- 4.5%, 26 +/- 2.8% and 49
      +/- 4.2% displayed immunopositive staining for choline acetyl transferase (ChAT),
      substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide synthetase
      (NOS), respectively. A bath application of EM2 (2 MUM) enhanced spontaneous
      contractile amplitude and tension, which were reversed by beta-FNA (an antagonist
      of MOR) but not NG-nitro-L-arginine methyl ether (L-NAME, a non-selective
      inhibitor of NOS) or VIP6-28 (an antagonist of the VIP receptor) in the colonic
      strips. EM2 significantly suppressed inhibitory junction potentials (IJPs) in 14
      of the 17 examined circular muscle cells, and this effect was not antagonized by
      preincubation in L-NAME. EM2 was widely expressed in interneurons and motor
      neurons in the myenteric plexus and presynaptically inhibited fast IJPs, thereby
      enhancing spontaneous contraction and tension in the colonic smooth muscle. 

PMID- 25565975
TI  - Localization of diacylglycerol lipase alpha and monoacylglycerol lipase during
      postnatal development of the rat retina.
AB  - In recent decades, there has been increased interest in the physiological roles
      of the endocannabinoid (eCB) system and its receptors, the cannabinoid receptor
      types 1 (CB1R) and 2 (CB2R). Exposure to cannabinoids during development results
      in neurofunctional alterations, which implies that the eCB system is involved in
      the developmental processes of the brain. Because of their lipophilic nature,
      eCBs are synthesized on demand and are not stored in vesicles. Consequently, the
      enzymes responsible for their synthesis and degradation are key regulators of
      their physiological actions. Therefore, knowing the localization of these enzymes
      during development is crucial for a better understanding of the role played by
      eCBs during the formation of the central nervous system. In this study, we
      investigated the developmental protein localization of the synthesizing and
      catabolic enzymes of the principal eCB, 2-arachidonoylglycerol (2-AG) in the
      retinas of young and adult rats. The distribution of the enzymes responsible for
      the synthesis (DAGLalpha) and the degradation (MAGL) of 2-AG was determined for
      every retinal cell type from birth to adulthood. Our results indicate that
      DAGLalpha is present early in postnatal development. It is highly expressed in
      photoreceptor, horizontal, amacrine, and ganglion cells. MAGL appears later
      during the development of the retina and its presence is limited to amacrine and
      Muller cells. Overall, these results suggest that 2-AG is strongly present in
      early retinal development and might be involved in the regulation of the
      structural and functional maturation of the retina. 

PMID- 25565976
TI  - Correlation between SD-OCT, immunocytochemistry and functional findings in an
      animal model of retinal degeneration.
AB  - PURPOSE: The P23H rhodopsin mutation is an autosomal dominant cause of retinitis
      pigmentosa (RP). The degeneration can be tracked using different anatomical and
      functional methods. In our case, we evaluated the anatomical changes using
      Spectral-Domain Optical Coherence Tomography (SD-OCT) and correlated the findings
      with retinal thickness values determined by immunocytochemistry. METHODS:
      Pigmented rats heterozygous for the P23H mutation, with ages between P18 and P180
      were studied. Function was assessed by means of optomotor testing and ERGs.
      Retinal thicknesses measurements, autofluorescence and fluorescein angiography
      were performed using Spectralis OCT. Retinas were studied by means of
      immunohistochemistry. RESULTS: Between P30 and P180, visual acuity decreased from
      0.500 to 0.182 cycles per degree (cyc/deg) and contrast sensitivity decreased
      from 54.56 to 2.98 for a spatial frequency of 0.089 cyc/deg. Only cone-driven b
      wave responses reached developmental maturity. Flicker fusions were also
      comparable at P29 (42 Hz). Double flash-isolated rod-driven responses were
      already affected at P29. Photopic responses revealed deterioration after P29.A
      reduction in retinal thicknesses and morphological modifications were seen in OCT
      sections. Statistically significant differences were found in all evaluated
      thicknesses. Autofluorescence was seen in P23H rats as sparse dots.
      Immunocytochemistry showed a progressive decrease in the outer nuclear layer
      (ONL), and morphological changes. Although anatomical thickness measures were
      significantly lower than OCT values, there was a very strong correlation between
      the values measured by both techniques. CONCLUSIONS: In pigmented P23H rats, a
      progressive deterioration occurs in both retinal function and anatomy. Anatomical
      changes can be effectively evaluated using SD-OCT and immunocytochemistry, with a
      good correlation between their values, thus making SD-OCT an important tool for
      research in retinal degeneration.

PMID- 25565978
TI  - The molecular evolutionary dynamics of the vomeronasal receptor (class 1) genes
      in primates: a gene family on the verge of a functional breakdown.
AB  - Olfaction plays a critical role in both survival of the individual and in the
      propagation of species. Studies from across the mammalian clade have found a
      remarkable correlation between organismal lifestyle and molecular evolutionary
      properties of receptor genes in both the main olfactory system (MOS) and the
      vomeronasal system (VNS). When a large proportion of intact (and putatively
      functional) copies is observed, the inference is made that a particular mode of
      chemoreception is critical for an organism's fit to its environment and is thus
      under strong positive selection. Conversely, when the receptors in question show
      a disproportionately large number of pseudogene copies, this contraction is
      interpreted as evidence of relaxed selection potentially leading to gene family
      extinction. Notably, it appears that a risk factor for gene family extinction is
      a high rate of nonsynonymous substitution. A survey of intact vs. pseudogene
      copies among primate vomeronasal receptor Class one genes (V1Rs) appears to
      substantiate this hypothesis. Molecular evolutionary complexities in the V1R gene
      family combine rapid rates of gene duplication, gene conversion, lineage-specific
      expansions, deletions, and/or pseudogenization. An intricate mix of phylogenetic
      footprints and current adaptive landscapes have left their mark on primate V1Rs
      suggesting that the primate clade offers an ideal model system for exploring the
      molecular evolutionary and functional properties of the VNS of mammals. Primate
      V1Rs tell a story of ancestral function and divergent selection as species have
      moved into ever diversifying adaptive regimes. The sensitivity to functional
      collapse in these genes, consequent to their precariously high rates of
      nonsynonymous substitution, confer a remarkable capacity to reveal the lifestyles
      of the genomes that they presently occupy as well as those of their ancestors. 

PMID- 25565979
TI  - Localization of SK2 channels relative to excitatory synaptic sites in the mouse
      developing Purkinje cells.
AB  - Small-conductance, Ca(2+)-activated K(+) (SK) channels regulate neuronal
      excitability in a variety of ways. To understand their roles in different
      neuronal subtypes it is important to determine their precise subcellular
      distribution. Here, we used biochemical, light microscopy immunohistochemical and
      immunoelectron microscopy techniques, combined with quantitative approaches, to
      reveal the expression and subcellular localization patterns of SK2 in the
      developing cerebellum. Using western blots, the SK2 protein showed a progressive
      increase during postnatal development. At the light microscopic level, SK2
      immunoreactivity was very prominent in the developing Purkinje cells (PC),
      particularly in the molecular layer (ML). Electron microscopy revealed that
      throughout development SK2 was mostly detected at the extrasynaptic and
      perisynaptic plasma membrane of dendritic shafts and dendritic spines of PCs.
      However, there was some localization at axon terminals as well. Quantitative
      analyses and 3D reconstructions further revealed a progressive developmental
      change of SK2 on the surface of PCs from dendritic shafts to dendritic spines.
      Together, these results indicate that SK2 channels undergo dynamic spatial
      regulation during cerebellar development, and this process is associated with the
      formation and maturation of excitatory synaptic contacts to PCs. 

PMID- 25565977
TI  - Molecular determinants of selective dopaminergic vulnerability in Parkinson's
      disease: an update.
AB  - Numerous disorders of the central nervous system (CNS) are attributed to the
      selective death of distinct neuronal cell populations. Interestingly, in many of
      these conditions, a specific subset of neurons is extremely prone to degeneration
      while other, very similar neurons are less affected or even spared for many
      years. In Parkinson's disease (PD), the motor manifestations are primarily linked
      to the selective, progressive loss of dopaminergic (DA) neurons in the substantia
      nigra pars compacta (SNpc). In contrast, the very similar DA neurons in the
      ventral tegmental area (VTA) demonstrate a much lower degree of degeneration.
      Elucidating the molecular mechanisms underlying the phenomenon of differential DA
      vulnerability in PD has proven extremely challenging. Moreover, an increasing
      number of studies demonstrate that considerable molecular and electrophysiologic
      heterogeneity exists among the DA neurons within the SNpc as well as those within
      the VTA, adding yet another layer of complexity to the selective DA vulnerability
      observed in PD. The discovery of key pathways that regulate this differential
      susceptibility of DA neurons to degeneration holds great potential for the
      discovery of novel drug targets and the development of promising neuroprotective
      treatment strategies. This review provides an update on the molecular basis of
      the differential vulnerability of midbrain DA neurons in PD and highlights the
      most recent developments in this field. 

PMID- 25565981
TI  - Dynamic expression of Notch-dependent neurogenic markers in the chick embryonic
      nervous system.
AB  - The establishment of a functional nervous system requires a highly orchestrated
      process of neural proliferation and differentiation. The evolutionary conserved
      Notch signaling pathway is a key regulator of this process, regulating basic
      helix-loop-helix (bHLH) transcriptional repressors and proneural genes. However,
      little is known about downstream Notch targets and subsequently genes required
      for neuronal specification. In this report, the expression pattern of Transgelin
      3 (Tagln3), Chromogranin A (Chga) and Contactin 2 (Cntn2) was described in detail
      during early chick embryogenesis. Expression of these genes was largely
      restricted to the nervous system including the early axon scaffold populations,
      cranial ganglia and spinal motor neurons. Their temporal and spatial expression
      were compared with the neuronal markers Nescient Helix-Loop-Helix 1 (Nhlh1),
      Stathmin 2 (Stmn2) and HuC/D. We show that Tagln3 is an early marker for post
      mitotic neurons whereas Chga and Cntn2 are expressed in mature neurons. We
      demonstrate that inhibition of Notch signaling during spinal cord neurogenesis
      enhances expression of these markers. This data demonstrates that Tagln3, Chga
      and Cntn2 represent strong new candidates to contribute to the sequential
      progression of vertebrate neurogenesis. 

PMID- 25565983
TI  - Neural representation of calling songs and their behavioral relevance in the
      grasshopper auditory system.
AB  - Acoustic communication plays a key role for mate attraction in grasshoppers.
      Males use songs to advertise themselves to females. Females evaluate the song
      pattern, a repetitive structure of sound syllables separated by short pauses, to
      recognize a conspecific male and as proxy to its fitness. In their natural
      habitat females often receive songs with degraded temporal structure.
      Perturbations may, for example, result from the overlap with other songs. We
      studied the response behavior of females to songs that show different signal
      degradations. A perturbation of an otherwise attractive song at later positions
      in the syllable diminished the behavioral response, whereas the same perturbation
      at the onset of a syllable did not affect song attractiveness. We applied naive
      Bayes classifiers to the spike trains of identified neurons in the auditory
      pathway to explore how sensory evidence about the acoustic stimulus and its
      attractiveness is represented in the neuronal responses. We find that populations
      of three or more neurons were sufficient to reliably decode the acoustic stimulus
      and to predict its behavioral relevance from the single-trial integrated firing
      rate. A simple model of decision making simulates the female response behavior.
      It computes for each syllable the likelihood for the presence of an attractive
      song pattern as evidenced by the population firing rate. Integration across
      syllables allows the likelihood to reach a decision threshold and to elicit the
      behavioral response. The close match between model performance and animal
      behavior shows that a spike rate code is sufficient to enable song pattern
      recognition. 

PMID- 25565980
TI  - Parkinson's disease: animal models and dopaminergic cell vulnerability.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder that affects about 1.5%
      of the global population over 65 years of age. A hallmark feature of PD is the
      degeneration of the dopamine (DA) neurons in the substantia nigra pars compacta
      (SNc) and the consequent striatal DA deficiency. Yet, the pathogenesis of PD
      remains unclear. Despite tremendous growth in recent years in our knowledge of
      the molecular basis of PD and the molecular pathways of cell death, important
      questions remain, such as: (1) why are SNc cells especially vulnerable; (2) which
      mechanisms underlie progressive SNc cell loss; and (3) what do Lewy bodies or
      alpha-synuclein reveal about disease progression. Understanding the variable
      vulnerability of the dopaminergic neurons from the midbrain and the mechanisms
      whereby pathology becomes widespread are some of the primary objectives of
      research in PD. Animal models are the best tools to study the pathogenesis of PD.
      The identification of PD-related genes has led to the development of genetic PD
      models as an alternative to the classical toxin-based ones, but does the
      dopaminergic neuronal loss in actual animal models adequately recapitulate that
      of the human disease? The selection of a particular animal model is very
      important for the specific goals of the different experiments. In this review, we
      provide a summary of our current knowledge about the different in vivo models of
      PD that are used in relation to the vulnerability of the dopaminergic neurons in
      the midbrain in the pathogenesis of PD. 

PMID- 25565982
TI  - Alpha-synuclein spreading in Parkinson's disease.
AB  - Formation and accumulation of misfolded protein aggregates are a central hallmark
      of several neurodegenerative diseases. In Parkinson's disease (PD), the
      aggregation-prone protein alpha-synuclein (alpha-syn) is the culprit. In the past
      few years, another piece of the puzzle has been added with data suggesting that
      alpha-syn may self-propagate, thereby contributing to the progression and
      extension of PD. Of particular importance, it was the seminal observation of Lewy
      bodies (LB), a histopathological signature of PD, in grafted fetal dopaminergic
      neurons in the striatum of PD patients. Consequently, these findings were a
      conceptual breakthrough, generating the "host to graft transmission" hypothesis,
      also called the "prion-like hypothesis." Several in vitro and in vivo studies
      suggest that alpha-syn can undergo a toxic templated conformational change,
      spread from cell to cell and from region to region, and initiate the formation of
      "LB-like aggregates," contributing to the PD pathogenesis. Here, we will review
      and discuss the current knowledge for such a putative mechanism on the prion-like
      nature of alpha-syn, and discuss about the proper use of the term prion-like. 

PMID- 25565984
TI  - Brain-machine interfaces as a challenge to the "moment of singularity".

PMID- 25565985
TI  - Sleep memory processing: the sequential hypothesis.
AB  - According to the sequential hypothesis (SH) memories acquired during wakefulness
      are processed during sleep in two serial steps respectively occurring during slow
      wave sleep (SWS) and rapid eye movement (REM) sleep. During SWS memories to be
      retained are distinguished from irrelevant or competing traces that undergo
      downgrading or elimination. Processed memories are stored again during REM sleep
      which integrates them with preexisting memories. The hypothesis received support
      from a wealth of EEG, behavioral, and biochemical analyses of trained rats.
      Further evidence was provided by independent studies of human subjects. SH basic
      premises, data, and interpretations have been compared with corresponding
      viewpoints of the synaptic homeostatic hypothesis (SHY). Their similarities and
      differences are presented and discussed within the framework of sleep processing
      operations. SHY's emphasis on synaptic renormalization during SWS is acknowledged
      to underline a key sleep effect, but this cannot marginalize sleep's main role in
      selecting memories to be retained from downgrading traces, and in their
      integration with preexisting memories. In addition, SHY's synaptic
      renormalization raises an unsolved dilemma that clashes with the accepted memory
      storage mechanism exclusively based on modifications of synaptic strength. This
      difficulty may be bypassed by the assumption that SWS-processed memories are
      stored again by REM sleep in brain subnuclear quantum particles. Storing of
      memories in quantum particles may also occur in other vigilance states. Hints are
      provided on ways to subject the quantum hypothesis to experimental tests. 

PMID- 25565988
TI  - The relationship between local field potentials (LFPs) and the electromagnetic
      fields that give rise to them.

PMID- 25565986
TI  - What we do not know about cerebellar systems neuroscience.
AB  - Our knowledge of the modular organization of the cerebellum and the sphere of
      influence of these modules still presents large gaps. Here I will review these
      gaps against our present anatomical and physiological knowledge of these systems.

PMID- 25565987
TI  - Sensorimotor restriction affects complex movement topography and reachable space
      in the rat motor cortex.
AB  - Long-duration intracortical microstimulation (ICMS) studies with 500 ms of
      current pulses suggest that the forelimb area of the motor cortex is organized
      into several spatially distinct functional zones that organize movements into
      complex sequences. Here we studied how sensorimotor restriction modifies the
      extent of functional zones, complex movements, and reachable space representation
      in the rat forelimb M1. Sensorimotor restriction was achieved by means of whole
      forelimb casting of 30 days duration. Long-duration ICMS was carried out 12 h and
      14 days after cast removal. Evoked movements were measured using a high
      resolution 3D optical system. Long-term cast caused: (i) a reduction in the
      number of sites where complex forelimb movement could be evoked; (ii) a shrinkage
      of functional zones but no change in their center of gravity; (iii) a reduction
      in movement with proximal/distal coactivation; (iv) a reduction in maximal
      velocity, trajectory and vector length of movement, but no changes in latency or
      duration; (v) a large restriction of reachable space. Fourteen days of forelimb
      freedom after casting caused: (i) a recovery of the number of sites where complex
      forelimb movement could be evoked; (ii) a recovery of functional zone extent and
      movement with proximal/distal coactivation; (iii) an increase in movement
      kinematics, but only partial restoration of control rat values; (iv) a slight
      increase in reachability parameters, but these remained far below baseline
      values. We pose the hypothesis that specific aspects of complex movement may be
      stored within parallel motor cortex re-entrant systems. 

PMID- 25565989
TI  - Spin-glass model predicts metastable brain states that diminish in anesthesia.
AB  - Patterns of resting state connectivity change dynamically and may represent modes
      of cognitive information processing. The diversity of connectivity patterns
      (global brain states) reflects the information capacity of the brain and
      determines the state of consciousness. In this work, computer simulation was used
      to explore the repertoire of global brain states as a function of cortical
      activation level. We implemented a modified spin glass model to describe UP/DOWN
      state transitions of neuronal populations at a mesoscopic scale based on resting
      state BOLD fMRI data. Resting state fMRI was recorded in 20 participants and
      mapped to 10,000 cortical regions (sites) defined on a group-aligned cortical
      surface map. Each site represented the population activity of a ~20 mm(2) area of
      the cortex. Cross-correlation matrices of the mapped BOLD time courses of the set
      of sites were calculated and averaged across subjects. In the model, each
      cortical site was allowed to interact with the 16 other sites that had the
      highest pair-wise correlation values. All sites stochastically transitioned
      between UP and DOWN states under the net influence of their 16 pairs. The
      probability of local state transitions was controlled by a single parameter T
      corresponding to the level of global cortical activation. To estimate the number
      of distinct global states, first we ran 10,000 simulations at T = 0. Simulations
      were started from random configurations that converged to one of several distinct
      patterns. Using hierarchical clustering, at 99% similarity, close to 300 distinct
      states were found. At intermediate T, metastable state configurations were formed
      suggesting critical behavior with a sharp increase in the number of metastable
      states at an optimal T. Both reduced activation (anesthesia, sleep) and increased
      activation (hyper-activation) moved the system away from equilibrium, presumably
      incompatible with conscious mentation. During equilibrium, the diversity of large
      scale brain states was maximum, compatible with maximum information capacity-a
      presumed condition of consciousness. 

PMID- 25565990
TI  - Propofol and sevoflurane induce distinct burst suppression patterns in rats.
AB  - Burst suppression is an EEG pattern characterized by alternating periods of high
      amplitude activity (bursts) and relatively low amplitude activity (suppressions).
      Burst suppression can arise from several different pathological conditions, as
      well as from general anesthesia. Here we review current algorithms that are used
      to quantify burst suppression, its various etiologies, and possible underlying
      mechanisms. We then review clinical applications of anesthetic-induced burst
      suppression. Finally, we report the results of our new study showing clear
      electrophysiological differences in burst suppression patterns induced by two
      common general anesthetics, sevoflurane and propofol. Our data suggest that the
      circuit mechanisms that generate burst suppression activity may differ among
      general anesthetics. 

PMID- 25565993
TI  - Enhancing cognition before clinical symptoms of dementia.

PMID- 25565992
TI  - Motion detection based on recurrent network dynamics.
AB  - The detection of visual motion requires temporal delays to compare current with
      earlier visual input. Models of motion detection assume that these delays reside
      in separate classes of slow and fast thalamic cells, or slow and fast synaptic
      transmission. We used a data-driven modeling approach to generate a model that
      instead uses recurrent network dynamics with a single, fixed temporal integration
      window to implement the velocity computation. This model successfully reproduced
      the temporal response dynamics of a population of motion sensitive neurons in
      macaque middle temporal area (MT) and its constituent parts matched many of the
      properties found in the motion processing pathway (e.g., Gabor-like receptive
      fields (RFs), simple and complex cells, spatially asymmetric excitation and
      inhibition). Reverse correlation analysis revealed that a simplified network
      based on first and second order space-time correlations of the recurrent model
      behaved much like a feedforward motion energy (ME) model. The feedforward model,
      however, failed to capture the full speed tuning and direction selectivity
      properties based on higher than second order space-time correlations typically
      found in MT. These findings support the idea that recurrent network connectivity
      can create temporal delays to compute velocity. Moreover, the model explains why
      the motion detection system often behaves like a feedforward ME network, even
      though the anatomical evidence strongly suggests that this network should be
      dominated by recurrent feedback. 

PMID- 25565994
TI  - Attentional selection of levels within hierarchically organized figures is
      mediated by object-files.
AB  - Objects frequently have a hierarchical organization (tree-branch-leaf). How do we
      select the level to be attended? This has been explored with compound letters: a
      global letter built from local letters. One explanation, backed by much empirical
      support, is that attentional competition is biased toward certain spatial
      frequency (SF) bands across all locations and objects (a SF filter). This view
      assumes that the global and local letters are carried respectively by low and
      high SF bands, and that the bias can persist over time. Here we advocate a
      complementary view in which perception of hierarchical level is determined by how
      we represent letters in object-files. Although many properties bound to an object
      file (i.e., position, color, even shape) can mutate without affecting its
      persistence over time, we posit that same object-file cannot be used to store
      information from different hierarchical levels. Thus, selection of level would be
      independent from locations but not from the way objects are represented at each
      moment. These views were contrasted via an attentional blink paradigm that
      presented letters within compound figures, but only one level at a time.
      Attending to two letters in rapid succession was easier if they were at the same
      compared to different-levels, as predicted by both accounts. However, only the
      object-file account was able to explain why it was easier to report two targets
      on the same moving object compared to the same targets on distinct objects. The
      interference of different masks on target recognition was also easier to predict
      by the object-file account than by an SF filter. The methods introduced here
      allowed us to investigate attention to hierarchical levels and to object-files
      within the same empirical framework. The data suggests that SF information is
      used to structure the internal organization of object representations, a process
      understood best by integrating object-file theory with previous models of
      hierarchical perception. 

PMID- 25565995
TI  - Preservation of common rhythmic locomotor control despite weakened supraspinal
      regulation after stroke.
AB  - The basic pattern of arm and leg movement during rhythmic locomotor tasks is
      supported by common central neural control from spinal and supraspinal centers in
      neurologically intact participants. The purpose of this study was to test the
      hypothesis that following a cerebrovascular accident, shared systems from
      interlimb cutaneous networks facilitating arm and leg coordination persist across
      locomotor tasks. Twelve stroke participants (>6 months post CVA) performed arm
      and leg (A&L) cycling using a stationary ergometer and walking on a motorized
      treadmill. In both tasks cutaneous reflexes were evoked via surface stimulation
      of the nerves innervating the dorsum of the hand (superficial radial; SR) and
      foot (superficial peroneal; SP) of the less affected limbs. Electromyographic
      (EMG) activity from the tibialis anterior, soleus, flexor carpi radialis, and
      posterior deltoid were recorded bilaterally with surface electrodes. Full-wave
      rectified and filtered EMG data were separated into eight equal parts or phases
      and aligned to begin with maximum knee extension for both walking and A&L
      cycling. At each phase of movement, background EMG data were quantified as the
      peak normalized response for each participant and cutaneous reflexes were
      quantified as the average cumulative reflex over 150 ms following stimulation. In
      general, background EMG was similar between walking and A&L cycling, seen
      especially in the distal leg muscles. Cutaneous reflexes were evident and
      modified in the less and more affected limbs during walking and A&L cycling and
      similar modulation patterns were observed suggesting activity in related control
      networks between tasks. After a stroke common neural patterning from conserved
      subcortical regulation is seen supporting the notion of a common core in
      locomotor tasks involving arm and leg movement. This has translational
      implications for rehabilitation where A&L cycling could be usefully applied to
      improve walking function. 

PMID- 25565997
TI  - Forced-choice decision-making in modified trolley dilemma situations: a virtual
      reality and eye tracking study.
AB  - Based on the frameworks of dual-process theories, we examined the interplay
      between intuitive and controlled cognitive processes related to moral and social
      judgments. In a virtual reality (VR) setting we performed an experiment
      investigating the progression from fast, automatic decisions towards more
      controlled decisions over multiple trials in the context of a sacrificing
      scenario. We repeatedly exposed participants to a modified ten-to-one version and
      to three one-to-one versions of the trolley dilemma in VR and varied avatar
      properties, such as their gender and ethnicity, and their orientation in space.
      We also investigated the influence of arousing music on decisions. Our experiment
      replicated the behavioral pattern observed in studies using text versions of the
      trolley dilemma, thereby validating the use of virtual environments in research
      on moral judgments. Additionally, we found a general tendency towards sacrificing
      male individuals which correlated with socially desirable responding. As
      indicated by differences in response times, the ten-to-one version of the trolley
      dilemma seems to be faster to decide than decisions requiring comparisons based
      on specific avatar properties as a result of differing moral content. Building
      upon research on music-based emotion induction, we used music to induce emotional
      arousal on a physiological level as measured by pupil diameter. We found a
      specific temporal signature displaying a peak in arousal around the moment of
      decision. This signature occurs independently of the overall arousal level.
      Furthermore, we found context-dependent gaze durations during sacrificing
      decisions, leading participants to look prolonged at their victim if they had to
      choose between avatars differing in gender. Our study confirmed that moral
      decisions can be explained within the framework of dual-process theories and
      shows that pupillometric measurements are a promising tool for investigating
      affective responses in dilemma situations. 

PMID- 25565996
TI  - 5-HT7 receptor signaling: improved therapeutic strategy in gut disorders.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) is most commonly known for its role as a
      neurotransmitter in the central nervous system (CNS). However, the majority of
      the body's 5-HT is produced in the gut by enterochromaffin (EC) cells.
      Alterations in 5-HT signaling have been associated with various gut disorders
      including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and
      enteric infections. Recently, our studies have identified a key role for 5-HT in
      the pathogenesis of experimental colitis. 5-HT7 receptors are expressed in the
      gut and very recently, we have shown evidence of 5-HT7 receptor expression on
      intestinal immune cells and demonstrated a key role for 5-HT7 receptors in
      generation of experimental colitis. This review summarizes the key findings of
      these studies and provides a comprehensive overview of our current knowledge of
      the 5-HT7 receptor in terms of its pathophysiological relevance and therapeutic
      potential in intestinal inflammatory conditions, such as IBD. 

PMID- 25565998
TI  - Differential responses to acute administration of a new 5-HT7-R agonist as a
      function of adolescent pre-treatment: phMRI and immuno-histochemical study.
AB  - LP-211 is a new, selective agonist of serotonin (5-hydroxytryptamine, 5-HT)
      receptor 7 (5-HT7-R), which is part of a neuro-transmission system with a
      proposed role in neural plasticity and in mood, cognitive and sleep regulation.
      Adolescent subchronic LP-211 treatment produces some persisting changes in rats'
      forebrain structural and functional parameters. Here, using pharmacological MRI
      (phMRI), we investigated the effect of acute administration with LP-211 (10 mg/kg
      i.p.), or vehicle, to adult rats previously exposed to the same drug (0.25
      mg/kg/day for 5 days), or vehicle, during adolescence (44-48 post-natal days);
      histology and immuno-histochemistry were performed ex vivo to evaluate neuro
      anatomical and physiological long-term adaptation to pharmacological pre
      treatment. The phMRI signal reveals forebrain areas (i.e., hippocampus, orbital
      prefrontal cortex), activated in response to LP-211 challenge independently of
      adolescent pre-treatment. In septum and nucleus accumbens, sensitized activation
      was found in adolescent pre-treated rats but not in vehicle-exposed controls.
      Immuno-histochemical analyses showed marked differences in septum as long-term
      consequence of the adolescent pre-treatment: increased level of 5-HT7-R,
      increased number of 5-HT7-R positive cells, and enhanced astrocyte activation.
      For nucleus accumbens, immuno-histochemical analyses did not reveal any
      difference between adolescent pre-treated rats and vehicle-exposed controls. In
      conclusion, subchronic LP-211 administration during adolescence is able to induce
      persistent physiological changes in the septal 5-HT7-R expression and astrocyte
      response that can still be observed in adulthood. Data shed new insights into
      roles of 5-HT7-R for normal and pathologic behavioral regulations. 

PMID- 25565991
TI  - Individual differences in response to positive and negative stimuli:
      endocannabinoid-based insight on approach and avoidance behaviors.
AB  - Approach and avoidance behaviors-the primary responses to the environmental
      stimuli of danger, novelty and reward-are associated with the brain structures
      that mediate cognitive functionality, reward sensitivity and emotional
      expression. Individual differences in approach and avoidance behaviors are
      modulated by the functioning of amygdaloid-hypothalamic-striatal and striatal
      cerebellar networks implicated in action and reaction to salient stimuli. The
      nodes of these networks are strongly interconnected and by acting on them the
      endocannabinoid and dopaminergic systems increase the intensity of appetitive or
      defensive motivation. This review analyzes the approach and avoidance behaviors
      in humans and rodents, addresses neurobiological and neurochemical aspects of
      these behaviors, and proposes a possible synaptic plasticity mechanism, related
      to endocannabinoid-dependent long-term potentiation (LTP) and depression that
      allows responding to salient positive and negative stimuli. 

PMID- 25566000
TI  - Relationship between L-DOPA-induced reduction in motor and exploratory activity
      and degree of DAT binding in the rat.
AB  - PURPOSE: The present study assessed the influence of L-DOPA administration on
      neostriatal dopamine (DA) transporter (DAT) binding in relation to motor and
      exploratory behaviors in the rat. METHODS: Rats received injections of 5 mg/kg L
      DOPA, 10 mg/kg L-DOPA or vehicle. Motor and exploratory behaviors were assessed
      for 30 min in an open field prior to administration of [(123)I]FP-CIT. Dopamine
      transporter binding was measured with small animal single-photon emission
      computed tomography (SPECT) 2 h after radioligand administration for 60 min.
      RESULTS: Both L-DOPA doses significantly reduced DAT binding and led to
      significantly less head-shoulder motility and more sitting relative to vehicle.
      Moreover, 10 mg/kg L-DOPA induced less distance traveled and ambulation than 5
      mg/kg L-DOPA. Analysis of time-behavior (t-b) curves showed that L-DOPA-treated
      animals relative to vehicle exhibited (1) a faster rate of increase in duration
      of sitting; (2) a slower rate of increase in duration of head-shoulder motility;
      and (3) a slower rate of decrease in frequency of head-shoulder motility.
      CONCLUSIONS: The reductions of striatal DAT binding after L-DOPA challenges
      reflected elevated concentrations of synaptic DA. L-DOPA-treated animals showed
      less head-shoulder motility and more sitting than vehicle-treated animals,
      indicating an association between less behavioral activity and increased
      availability of striatal DA. The faster increase of sitting duration to a higher
      final level and the slower increase of head-shoulder motility to a lower final
      level relative to controls may be interpreted in terms on behavioral habituation
      to a novel environment.

PMID- 25566002
TI  - Physiological and behavioral patterns of corruption.
AB  - We study the behavior and emotional arousal of the participants in an
      experimental auction, leading to an asymmetric social dilemma involving an
      auctioneer and two bidders. An antisocial transfer (bribe) which is beneficial
      for the auctioneer (official) is paid, if promised, by the winner of the auction.
      Some pro-social behavior on both the auctioneers' and the bidders' sides is
      observed even in the absence of any punishment mechanism (Baseline, Treatment 0).
      However, pro-social behavior is adopted by the vast majority of subjects when the
      loser of the auction can inspect the transaction between the winner and the
      auctioneer (Inspection, Treatment 1). The inspection and punishment mechanism is
      such that, if a bribe is (not) revealed, both corrupt agents (the denouncing
      bidder) lose(s) this period's payoffs. This renders the inspection option
      unprofitable for the loser and is rarely used, especially toward the end of the
      session, when pro-social behavior becomes pervasive. Subjects' emotional arousal
      was obtained through skin conductance responses. Generally speaking, our findings
      suggest that stronger emotions are associated with decisions deviating from pure
      monetary reward maximization, rather than with (un)ethical behavior per se. In
      fact, using response times as a measure of the subject's reflection during the
      decision-making process, we can associate emotional arousal with the conflict
      between primary or instinctive and secondary or contemplative motivations and,
      more specifically, with deviations from the subject's pure monetary interest. 

PMID- 25565999
TI  - State-dependent MU-opioid modulation of social motivation.
AB  - Social mammals engage in affiliative interactions both when seeking relief from
      negative affect and when searching for pleasure and joy. These two motivational
      states are both modulated by MU-opioid transmission. The MU-opioid receptor (MOR)
      system in the brain mediates pain relief and reward behaviors, and is implicated
      in social reward processing and affiliative bonding across mammalian species.
      However, pharmacological manipulation of the MU-opioid system has yielded
      opposite effects on rodents and primates: in rodents, social motivation is
      generally increased by MOR agonists and reduced by antagonists, whereas the
      opposite pattern has been shown in primates. Here, we address this paradox by
      taking into account differences in motivational state. We first review evidence
      for MU-opioid mediation of reward processing, emotion regulation, and affiliation
      in humans, non-human primates, rodents and other species. Based on the consistent
      cross-species similarities in opioid functioning, we propose a unified, state
      dependent model for MU-opioid modulation of affiliation across the mammalian
      species. Finally, we show that this state-dependent model is supported by
      evidence from both rodent and primate studies, when species and age differences
      in social separation response are taken into account. 

PMID- 25566003
TI  - Schizophrenia: a consequence of gene-environment interactions?

PMID- 25566001
TI  - Impulsive actions and choices in laboratory animals and humans: effects of high
      vs. low dopamine states produced by systemic treatments given to neurologically
      intact subjects.
AB  - Increases and decreases in dopamine (DA) transmission have both been suggested to
      influence reward-related impulse-control. The present literature review suggests
      that, in laboratory animals, the systemic administration of DA augmenters
      preferentially increases susceptibility to premature responding; with continued
      DA transmission, reward approach behaviors are sustained. Decreases in DA
      transmission, in comparison, diminish the appeal of distal and difficult to
      obtain rewards, thereby increasing susceptibility to temporal discounting and
      other forms of impulsive choice. The evidence available in humans is not
      incompatible with this model but is less extensive. 

PMID- 25566004
TI  - Language and cognition.

PMID- 25566005
TI  - Menthol facilitates the intravenous self-administration of nicotine in rats.
AB  - Menthol is preferred by ~25% of smokers and is the most common flavoring additive
      in tobacco and electronic cigarettes. Although some clinical studies have
      suggested that menthol facilitates the initiation of smoking and enhances the
      dependence on nicotine, many controversies remain. Using licking as the operant
      behavior, we found that adolescent rats self-administering nicotine
      (30MUg/kg/infusion, free base, i.v.) with contingent oral menthol (60MUl, 0.01%
      w/v) obtained significantly more infusions than rats receiving a vehicle cue or
      rats self-administering i.v. saline with a menthol cue. Rats yoked to their
      menthol-nicotine masters emitted significantly fewer licks on the active spouts,
      indicating that contingent pairing between nicotine and menthol is required for
      sustained nicotine intake. Rats that self-administered nicotine with a menthol
      cue also exhibited a long-lasting extinction burst and robust reinstatement
      behavior, neither of which were observed in rats that self-administered saline
      with a menthol cue. The cooling sensation of menthol is induced by activating the
      transient receptor potential M8 (TRPM8) channel. When WS-23, an odorless agonist
      of the TRPM8 channel, was used as a contingent cue for nicotine, the rats
      obtained a similar number of nicotine infusions as the rats that were provided a
      menthol cue and exhibited a strong preference for the active spout. In contrast,
      highly appetitive taste and odor cues failed to support nicotine self
      administration. These data indicated that menthol, likely by inducing a cooling
      sensation, becomes a potent conditioned reinforcer when it is contingently
      delivered with nicotine. Together, these results provide a key behavioral
      mechanism by which menthol promotes the use of tobacco products or electronic
      cigarettes. 

PMID- 25566006
TI  - Methamphetamine-induced short-term increase and long-term decrease in spatial
      working memory affects protein Kinase M zeta (PKMzeta), dopamine, and glutamate
      receptors.
AB  - Methamphetamine (MA) is a toxic, addictive drug shown to modulate learning and
      memory, yet the neural mechanisms are not fully understood. We investigated the
      effects of 2 weekly injections of MA (30 mg/kg) on working memory using the
      radial 8-arm maze (RAM) across 5 weeks in adolescent-age mice. MA-treated mice
      show a significant improvement in working memory performance 1 week following the
      first MA injection compared to saline-injected controls. Following 5 weeks of MA
      abstinence mice were re-trained on a reference and working memory version of the
      RAM to assess cognitive flexibility. MA-treated mice show significantly more
      working memory errors without effects on reference memory performance. The
      hippocampus and dorsal striatum were assessed for expression of glutamate
      receptors subunits, GluA2 and GluN2B; dopamine markers, dopamine 1 receptor (D1),
      dopamine transporter (DAT) and tyrosine hydroxylase (TH); and memory markers,
      protein kinase M zeta (PKMzeta) and protein kinase C zeta (PKCzeta). Within the
      hippocampus, PKMzeta and GluA2 are both significantly reduced after MA supporting
      the poor memory performance. Additionally, a significant increase in GluN2B and
      decrease in D1 identifies dysregulated synaptic function. In the striatum, MA
      treatment increased cytosolic DAT and TH levels associated with dopamine
      hyperfunction. MA treatment significantly reduced GluN2B while increasing both
      PKMzeta and PKCzeta within the striatum. We discuss the potential role of
      PKMzeta/PKCzeta in modulating dopamine and glutamate receptors after MA
      treatment. These results identify potential underlying mechanisms for working
      memory deficits induced by MA. 

PMID- 25566009
TI  - Cognitive deficits in schizophrenia and other neuropsychiatric disorders:
      convergence of preclinical and clinical evidence.

PMID- 25566007
TI  - Elevated cerebrospinal fluid 5-hydroxyindoleacetic acid in macaques following
      early life stress and inverse association with hippocampal volume: preliminary
      implications for serotonin-related function in mood and anxiety disorders.
AB  - BACKGROUND: Early life stress (ELS) is cited as a risk for mood and anxiety
      disorders, potentially through altered serotonin neurotransmission. We examined
      the effects of ELS, utilizing the variable foraging demand (VFD) macaque model,
      on adolescent monoamine metabolites. We sought to replicate an increase in
      cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) observed in two
      previous VFD cohorts. We hypothesized that elevated cisternal 5-HIAA was
      associated with reduced neurotrophic effects, conceivably due to excessive
      negative feedback at somatodendritic 5-HT1A autoreceptors. A putatively decreased
      serotonin neurotransmission would be reflected by reductions in hippocampal
      volume and white matter (WM) fractional anisotropy (FA). METHODS: When infants
      were 2-6 months of age, bonnet macaque mothers were exposed to VFD. We employed
      cisternal CSF taps to measure monoamine metabolites in VFD (N = 22) and non-VFD
      (N = 14) offspring (mean age = 2.61 years). Metabolites were correlated with
      hippocampal volume obtained by MRI and WM FA by diffusion tensor imaging in young
      adulthood in 17 males [10 VFD (mean age = 4.57 years)]. RESULTS: VFD subjects
      exhibited increased CSF 5-HIAA compared to non-VFD controls. An inverse
      correlation between right hippocampal volume and 5-HIAA was noted in VFD- but not
      controls. CSF HVA and MHPG correlated inversely with hippocampal volume only in
      VFD. CSF 5-HIAA correlated inversely with FA of the WM tracts of the anterior
      limb of the internal capsule (ALIC) only in VFD. CONCLUSIONS: Elevated cisternal
      5-HIAA in VFD may reflect increased dorsal raphe serotonin, potentially inducing
      excessive autoreceptor activation, inducing a putative serotonin deficit in
      terminal fields. Resultant reductions in neurotrophic activity are reflected by
      smaller right hippocampal volume. Convergent evidence of reduced neurotrophic
      activity in association with high CSF 5-HIAA in VFD was reflected by reduced FA
      of the ALIC.

PMID- 25566008
TI  - Increased conditioned place preference for cocaine in high anxiety related
      behavior (HAB) mice is associated with an increased activation in the accumbens
      corridor.
AB  - Anxiety disorders and substance use disorders are strongly associated in humans.
      Accordingly, a widely held but controversial concept in the addiction field, the
      so-called "self-medication hypothesis," posits that anxious individuals are more
      vulnerable for drug dependence because they use drugs of abuse to alleviate their
      anxiety. We tested this hypothesis under controlled experimental conditions by
      quantifying the conditioned place preference (CPP) to 15 mg/kg i.p. cocaine given
      contingently (COCAINE) in CD1 mice selectively bred for high anxiety-related
      behavior (HAB) vs. normal anxiety-related behavior (NAB). Cocaine was conditioned
      to the initially non-preferred compartment in an alternate day design (cocaine
      vs. saline, four pairings each). HAB and NAB mice were also tested for the
      effects of non-contingent (NONCONT) cocaine administration. HAB mice showed a
      slightly higher bias for one of the conditioning compartments during the pretest
      than NAB mice that became statistically significant (p = 0.045) only after
      pooling COCAINE and NONCONT groups. Cocaine CPP was higher (p = 0.0035) in HAB
      compared to NAB mice. The increased cocaine CPP was associated with an increased
      expression of the immediate early genes (IEGs) c-Fos and Early Growth Related
      Protein 1 (EGR1) in the accumbens corridor, i.e., a region stretching from the
      anterior commissure to the interhemispheric border and comprising the medial
      nucleus accumbens core and shell, the major island of Calleja and intermediate
      part of the lateral septum, as well as the vertical limb of the diagonal band and
      medial septum. The cocaine CPP-induced EGR1 expression was only observed in D1-
      and D2-medium spiny neurons, whereas other types of neurons or glial cells were
      not involved. With respect to the activation by contingent vs. non-contingent
      cocaine EGR1 seemed to be a more sensitive marker than c-Fos. Our findings
      suggest that cocaine may be more rewarding in high anxiety individuals, plausibly
      due to an anxiolytic effect. 

PMID- 25566010
TI  - Tactile priming modulates the activation of the fronto-parietal circuit during
      tactile angle match and non-match processing: an fMRI study.
AB  - The repetition of a stimulus task reduces the neural activity within certain
      cortical regions responsible for working memory (WM) processing. Although
      previous evidence has shown that repeated vibrotactile stimuli reduce the
      activation in the ventrolateral prefrontal cortex, whether the repeated tactile
      spatial stimuli triggered the priming effect correlated with the same cortical
      region remains unclear. Therefore, we used event-related functional magnetic
      resonance imaging (fMRI) and a delayed match-to-sample task to investigate the
      contributions of the priming effect to tactile spatial WM processing. Fourteen
      healthy volunteers were asked to encode three tactile angle stimuli during the
      encoding phase and one tactile angle stimulus during the recognition phase. Then,
      they answered whether the last angle stimulus was presented during the encoding
      phase. As expected, both the Match and Non-Match tasks activated a similar
      cerebral network. The critical new finding was decreased brain activity in the
      left inferior frontal gyrus (IFG), the right posterior parietal cortex (PPC) and
      bilateral medial frontal gyri (mFG) for the match task compared to the Non-Match
      task. Therefore, we suggest that the tactile priming engaged repetition
      suppression mechanisms during tactile angle matching, and this process decreased
      the activation of the fronto-parietal circuit, including IFG, mFG and PPC. 

PMID- 25566011
TI  - Brain stimulation for treatment and enhancement in children: an ethical analysis.
AB  - Davis (2014) called for "extreme caution" in the use of non-invasive brain
      stimulation (NIBS) to treat neurological disorders in children, due to gaps in
      scientific knowledge. We are sympathetic to his position. However, we must also
      address the ethical implications of applying this technology to minors.
      Compensatory trade-offs associated with NIBS present a challenge to its use in
      children, insofar as these trade-offs have the effect of limiting the child's
      future options. The distinction between treatment and enhancement has some
      normative force here. As the intervention moves away from being a treatment
      toward being an enhancement-and thus toward a more uncertain weighing of the
      benefits, risks, and costs-considerations of the child's best interests (as
      judged by the parents) diminish, and the need to protect the child's (future)
      autonomy looms larger. NIBS for enhancement involving trade-offs should therefore
      be delayed, if possible, until the child reaches a state of maturity and can make
      an informed, personal decision. NIBS for treatment, by contrast, is permissible
      insofar as it can be shown to be at least as safe and effective as currently
      approved treatments, which are themselves justified on a best interests standard.

PMID- 25566013
TI  - Does musical enrichment enhance the neural coding of syllables? Neuroscientific
      interventions and the importance of behavioral data.

PMID- 25566012
TI  - Mapping the brain's metaphor circuitry: metaphorical thought in everyday reason.
AB  - An overview of the basics of metaphorical thought and language from the
      perspective of Neurocognition, the integrated interdisciplinary study of how
      conceptual thought and language work in the brain. The paper outlines a theory of
      metaphor circuitry and discusses how everyday reason makes use of embodied
      metaphor circuitry. 

PMID- 25566014
TI  - Non-conscious visual cues related to affect and action alter perception of effort
      and endurance performance.
AB  - The psychobiological model of endurance performance proposes that endurance
      performance is determined by a decision-making process based on perception of
      effort and potential motivation. Recent research has reported that effort-based
      decision-making during cognitive tasks can be altered by non-conscious visual
      cues relating to affect and action. The effects of these non-conscious visual
      cues on effort and performance during physical tasks are however unknown. We
      report two experiments investigating the effects of subliminal priming with
      visual cues related to affect and action on perception of effort and endurance
      performance. In Experiment 1 thirteen individuals were subliminally primed with
      happy or sad faces as they cycled to exhaustion in a counterbalanced and
      randomized crossover design. A paired t-test (happy vs. sad faces) revealed that
      individuals cycled significantly longer (178 s, p = 0.04) when subliminally
      primed with happy faces. A 2 * 5 (condition * iso-time) ANOVA also revealed a
      significant main effect of condition on rating of perceived exertion (RPE) during
      the time to exhaustion (TTE) test with lower RPE when subjects were subliminally
      primed with happy faces (p = 0.04). In Experiment 2, a single-subject
      randomization tests design found that subliminal priming with action words
      facilitated a significantly longer TTE (399 s, p = 0.04) in comparison to
      inaction words. Like Experiment 1, this greater TTE was accompanied by a
      significantly lower RPE (p = 0.03). These experiments are the first to show that
      subliminal visual cues relating to affect and action can alter perception of
      effort and endurance performance. Non-conscious visual cues may therefore
      influence the effort-based decision-making process that is proposed to determine
      endurance performance. Accordingly, the findings raise notable implications for
      individuals who may encounter such visual cues during endurance competitions,
      training, or health related exercise. 

PMID- 25566015
TI  - Magnetoencephalography detection of high-frequency oscillations in the developing
      brain.
AB  - Increasing evidence from invasive intracranial recordings suggests that the
      matured brain generates both physiological and pathological high-frequency
      signals. The present study was designed to detect high-frequency brain signals in
      the developing brain using newly developed magnetoencephalography (MEG) methods.
      Twenty healthy children were studied with a high-sampling rate MEG system.
      Functional high-frequency brain signals were evoked by electrical stimulation
      applied to the index fingers. To determine if the high-frequency neuromagnetic
      signals are true brain responses in high-frequency range, we analyzed the MEG
      data using the conventional averaging as well as newly developed time-frequency
      analysis along with beamforming. The data of healthy children showed that very
      high-frequency brain signals (>1000 Hz) in the somatosensory cortex in the
      developing brain could be detected and localized using MEG. The amplitude of very
      high-frequency brain signals was significantly weaker than that of the low
      frequency brain signals. Very high-frequency brain signals showed a much earlier
      latency than those of a low-frequency. Magnetic source imaging (MSI) revealed
      that a portion of the high-frequency signals was from the somatosensory cortex,
      another portion of the high-frequency signals was probably from the thalamus. Our
      results provide evidence that the developing brain generates high-frequency
      signals that can be detected with the non-invasive technique of MEG. MEG
      detection of high-frequency brain signals may open a new window for the study of
      developing brain function. 

PMID- 25566017
TI  - Cerebral oscillatory activity during simulated driving using MEG.
AB  - We aimed to examine cerebral oscillatory differences associated with
      psychological processes during simulated car driving. We recorded neuromagnetic
      signals in 14 healthy volunteers using magnetoencephalography (MEG) during
      simulated driving. MEG data were analyzed using synthetic aperture magnetometry
      to detect the spatial distribution of cerebral oscillations. Group effects
      between subjects were analyzed statistically using a non-parametric permutation
      test. Oscillatory differences were calculated by comparison between "passive
      viewing" and "active driving." "Passive viewing" was the baseline, and
      oscillatory differences during "active driving" showed an increase or decrease in
      comparison with a baseline. Power increase in the theta band was detected in the
      superior frontal gyrus (SFG) during active driving. Power decreases in the alpha,
      beta, and low gamma bands were detected in the right inferior parietal lobe
      (IPL), left postcentral gyrus (PoCG), middle temporal gyrus (MTG), and posterior
      cingulate gyrus (PCiG) during active driving. Power increase in the theta band in
      the SFG may play a role in attention. Power decrease in the right IPL may reflect
      selectively divided attention and visuospatial processing, whereas that in the
      left PoCG reflects sensorimotor activation related to driving manipulation. Power
      decreases in the MTG and PCiG may be associated with object recognition. 

PMID- 25566016
TI  - Anatomical and functional plasticity in early blind individuals and the mixture
      of experts architecture.
AB  - As described elsewhere in this special issue, recent advances in neuroimaging
      over the last decade have led to a rapid expansion in our knowledge of anatomical
      and functional correlations within the normal and abnormal human brain. Here, we
      review how early blindness has been used as a model system for examining the role
      of visual experience in the development of anatomical connections and functional
      responses. We discuss how lack of power in group comparisons may provide a
      potential explanation for why extensive anatomical changes in cortico-cortical
      connectivity are not observed. Finally we suggest a framework-cortical
      specialization via hierarchical mixtures of experts-which offers some promise in
      reconciling a wide range of functional and anatomical data. 

PMID- 25566018
TI  - Non-rigid illusory contours and global shape transformations defined by
      spatiotemporal boundary formation.
AB  - Spatiotemporal boundary formation (SBF) is the perception of form, global motion,
      and continuous boundaries from relations of discrete changes in local texture
      elements (Shipley and Kellman, 1994). In two experiments, small, circular
      elements underwent small displacements whenever an edge of an invisible (virtual)
      object passed over them. Unlike previous studies that examined only rigidly
      translating objects, we tested virtual objects whose properties changed
      continuously. Experiment 1 tested rigid objects that changed in orientation,
      scale, and velocity. Experiment 2 tested objects that transformed non-rigidly
      taking on a series of shapes. Robust SBF occurred for all of the rigid
      transformations tested, as well as for non-rigid virtual objects, producing the
      perception of continuously bounded, smoothly deforming shapes. These novel
      illusions involve perhaps the most extreme cases of visual perception of
      continuous boundaries and shape from minimal information. They show that SBF
      encompasses a wider range of illusory phenomena than previously understood, and
      they present substantial challenges for existing models of SBF. 

PMID- 25566020
TI  - Neurofeedback of slow cortical potentials: neural mechanisms and feasibility of a
      placebo-controlled design in healthy adults.
AB  - To elucidate basic mechanisms underlying neurofeedback we investigated neural
      mechanisms of training of slow cortical potentials (SCPs) by considering EEG- and
      fMRI. Additionally, we analyzed the feasibility of a double-blind, placebo
      controlled design in NF research based on regulation performance during treatment
      sessions and self-assessment of the participants. Twenty healthy adults
      participated in 16 sessions of SCPs training: 9 participants received regular SCP
      training, 11 participants received sham feedback. At three time points (pre,
      intermediate, post) fMRI and EEG/ERP-measurements were conducted during a
      continuous performance test (CPT). Performance-data during the sessions
      (regulation performance) in the treatment group and the placebo group were
      analyzed. Analysis of EEG-activity revealed in the SCP group a strong enhancement
      of the CNV (electrode Cz) at the intermediate assessment, followed by a decrease
      back to baseline at the post-treatment assessment. In contrast, in the placebo
      group a continuous but smaller increase of the CNV could be obtained from pre to
      post assessment. The increase of the CNV in the SCP group at intermediate testing
      was superior to the enhancement in the placebo group. The changes of the CNV were
      accompanied by a continuous improvement in the test performance of the CPT from
      pre to intermediate to post assessment comparable in both groups. The change of
      the CNV in the SCP group is interpreted as an indicator of neural plasticity and
      efficiency while an increase of the CNV in the placebo group might reflect
      learning and improved timing due to the frequent task repetition. In the fMRI
      analysis evidence was obtained for neuronal plasticity. After regular SCP
      neurofeedback activation in the posterior parietal cortex decreased from the pre-
      to the intermediate measurement and increased again in the post measurement,
      inversely following the U-shaped increase and decrease of the tCNV EEG amplitude
      in the SCP-trained group. Furthermore, we found a localized increase of activity
      in the anterior cingulate cortex (ACC). Analyses of the estimation of treatment
      assignment by the participants indicate feasibility of blinding. Participants
      could not assess treatment assignment confidently. Participants of the SCP-group
      improved regulation capability during treatment sessions (in contrast to the
      participants of the placebo-group), although regulation capability appeared to be
      instable, presumably due to diminished confidence in the training (SCP- or sham
      training). Our results indicate that SCP training in healthy adults might lead to
      functional changes in neuronal circuits serving cognitive preparation even after
      a limited number of sessions. 

PMID- 25566022
TI  - Morphological priming during language switching: an ERP study.
AB  - Bilingual language control (BLC) is a much-debated issue in recent literature.
      Some models assume BLC is achieved by various types of inhibition of the non
      target language, whereas other models do not assume any inhibitory mechanisms. In
      an event-related potential (ERP) study involving a long-lag morphological priming
      paradigm, participants were required to name pictures and read aloud words in
      both their L1 (Dutch) and L2 (English). Switch blocks contained intervening L1
      items between L2 primes and targets, whereas non-switch blocks contained only L2
      stimuli. In non-switch blocks, target picture names that were morphologically
      related to the primes were named faster than unrelated control items. In switch
      blocks, faster response latencies were recorded for morphologically related
      targets as well, demonstrating the existence of morphological priming in the L2.
      However, only in non-switch blocks, ERP data showed a reduced N400 trend,
      possibly suggesting that participants made use of a post-lexical checking
      mechanism during the switch block. 

PMID- 25566021
TI  - Novel insights into the rehabilitation of memory post acquired brain injury: a
      systematic review.
AB  - OBJECTIVE: Acquired Brain Injury (ABI) frequently results in memory impairment
      causing significant disabilities in daily life and is therefore a critical target
      for cognitive rehabilitation. Current understanding of brain plasticity has led
      to novel insights in remediation-oriented approaches for the rehabilitation of
      memory deficits. We will describe 3 of these approaches that have emerged in the
      last decade: Virtual Reality (VR) training, Computer-Based Cognitive Retraining
      (CBCR) and Non-Invasive Brain Stimulation (NBS) and evaluate its effectiveness.
      METHODS: A systematic literature search was completed in regard to studies
      evaluating interventions aiming to improve the memory function after ABI.
      Information concerning study content and reported effectiveness were extracted.
      Quality of the studies and methods were evaluated. RESULTS: A total of 786
      studies were identified, 15 studies met the inclusion criteria. Three of those
      studies represent the VR technique, 7 studies represent CBCR and 5 studies NBS.
      All 3 studies found a significant improvement of the memory function after VR
      based training, however these studies are considered preliminary. All 7 studies
      have shown that CBCR can be effective in improving memory function in patients
      suffering from ABI. Four studies of the 5 did not find significant improvement of
      the memory function after the use of NBS in ABI patients. CONCLUSION: On the
      basis of this review, CBCR is considered the most promising novel approach of the
      last decade because of the positive results in improving memory function post
      ABI. The number of studies representing VR were limited and the methodological
      quality low, therefore the results should be considered preliminary. The studies
      representing NBS did not detect evidence for the use of NBS in improving memory
      function.

PMID- 25566023
TI  - A common framework for the analysis of complex motion? Standstill and capture
      illusions.
AB  - A series of illusions was created by presenting stimuli, which consisted of two
      overlapping surfaces each defined by textures of independent visual features
      (i.e., modulation of luminance, color, depth, etc.). When presented concurrently
      with a stationary 2-D luminance texture, observers often fail to perceive the
      motion of an overlapping stereoscopically defined depth-texture. This illusory
      motion standstill arises due to a failure to represent two independent surfaces
      (one for luminance and one for depth textures) and motion transparency (the
      ability to perceive motion of both surfaces simultaneously). Instead the stimulus
      is represented as a single non-transparent surface taking on the stationary
      nature of the luminance-defined texture. By contrast, if it is the 2D-luminance
      defined texture that is in motion, observers often perceive the stationary depth
      texture as also moving. In this latter case, the failure to represent the motion
      transparency of the two textures gives rise to illusionary motion capture. Our
      past work demonstrated that the illusions of motion standstill and motion capture
      can occur for depth-textures that are rotating, or expanding / contracting, or
      else spiraling. Here I extend these findings to include stereo-shearing. More
      importantly, it is the motion (or lack thereof) of the luminance texture that
      determines how the motion of the depth will be perceived. This observation is
      strongly in favor of a single pathway for complex motion that operates on
      luminance-defines texture motion signals only. In addition, these complex motion
      illusions arise with chromatically-defined textures with smooth transitions
      between their colors. This suggests that in respect to color motion perception
      the complex motions' pathway is only able to accurately process signals from
      isoluminant colored textures with sharp transitions between colors, and/or moving
      at high speeds, which is conceivable if it relies on inputs from a hypothetical
      dual opponent color pathway. 

PMID- 25566019
TI  - BDNF mediates improvements in executive function following a 1-year exercise
      intervention.
AB  - Executive function declines with age, but engaging in aerobic exercise may
      attenuate decline. One mechanism by which aerobic exercise may preserve executive
      function is through the up-regulation of brain-derived neurotropic factor (BDNF),
      which also declines with age. The present study examined BDNF as a mediator of
      the effects of a 1-year walking intervention on executive function in 90 older
      adults (mean age = 66.82). Participants were randomized to a stretching and
      toning control group or a moderate intensity walking intervention group. BDNF
      serum levels and performance on a task-switching paradigm were collected at
      baseline and follow-up. We found that age moderated the effect of intervention
      group on changes in BDNF levels, with those in the highest age quartile showing
      the greatest increase in BDNF after 1-year of moderate intensity walking exercise
      (p = 0.036). The mediation analyses revealed that BDNF mediated the effect of the
      intervention on task-switch accuracy, but did so as a function of age, such that
      exercise-induced changes in BDNF mediated the effect of exercise on task-switch
      performance only for individuals over the age of 71. These results demonstrate
      that both age and BDNF serum levels are important factors to consider when
      investigating the mechanisms by which exercise interventions influence cognitive
      outcomes, particularly in elderly populations. 

PMID- 25566024
TI  - Association with emotional information alters subsequent processing of neutral
      faces.
AB  - The processing of emotional as compared to neutral information is associated with
      different patterns in eye movement and neural activity. However, the
      'emotionality' of a stimulus can be conveyed not only by its physical properties,
      but also by the information that is presented with it. There is very limited work
      examining the how emotional information may influence the immediate perceptual
      processing of otherwise neutral information. We examined how presenting an
      emotion label for a neutral face may influence subsequent processing by using eye
      movement monitoring (EMM) and magnetoencephalography (MEG) simultaneously.
      Participants viewed a series of faces with neutral expressions. Each face was
      followed by a unique negative or neutral sentence to describe that person, and
      then the same face was presented in isolation again. Viewing of faces paired with
      a negative sentence was associated with increased early viewing of the eye region
      and increased neural activity between 600 and 1200 ms in emotion processing
      regions such as the cingulate, medial prefrontal cortex, and amygdala, as well as
      posterior regions such as the precuneus and occipital cortex. Viewing of faces
      paired with a neutral sentence was associated with increased activity in the
      parahippocampal gyrus during the same time window. By monitoring behavior and
      neural activity within the same paradigm, these findings demonstrate that
      emotional information alters subsequent visual scanning and the neural systems
      that are presumably invoked to maintain a representation of the neutral
      information along with its emotional details. 

PMID- 25566025
TI  - Asynchronous recruitment of low-threshold motor units during repetitive, low
      current stimulation of the human tibial nerve.
AB  - Motoneurons receive a barrage of inputs from descending and reflex pathways. Much
      of our understanding about how these inputs are transformed into motor output in
      humans has come from recordings of single motor units during voluntary
      contractions. This approach, however, is limited because the input is ill
      defined. Herein, we quantify the discharge of soleus motor units in response to
      well-defined trains of afferent input delivered at physiologically-relevant
      frequencies. Constant frequency stimulation of the tibial nerve (10-100 Hz for 30
      s), below threshold for eliciting M-waves or H-reflexes with a single pulse,
      recruited motor units in 7/9 subjects. All 25 motor units recruited during
      stimulation were also recruited during weak (<10% MVC) voluntary contractions.
      Higher frequencies recruited more units (n = 3/25 at 10 Hz; n = 25/25 at 100 Hz)
      at shorter latencies (19.4 +/- 9.4 s at 10 Hz; 4.1 +/- 4.0 s at 100 Hz) than
      lower frequencies. When a second unit was recruited, the discharge of the already
      active unit did not change, suggesting that recruitment was not due to increased
      synaptic drive. After recruitment, mean discharge rate during stimulation at 20
      Hz (7.8 Hz) was lower than during 30 Hz (8.6 Hz) and 40 Hz (8.4 Hz) stimulation.
      Discharge was largely asynchronous from the stimulus pulses with "time-locked"
      discharge occurring at an H-reflex latency with only a 24% probability. Motor
      units continued to discharge after cessation of the stimulation in 89% of trials,
      although at a lower rate (5.8 Hz) than during the stimulation (7.9 Hz). This work
      supports the idea that the afferent volley evoked by repetitive stimulation
      recruits motor units through the integration of synaptic drive and intrinsic
      properties of motoneurons, resulting in "physiological" recruitment which adheres
      to Henneman's size principle and results in relatively low discharge rates and
      asynchronous firing. 

PMID- 25566026
TI  - Your body, my body, our coupling moves our bodies.

PMID- 25566027
TI  - EEG-based local brain activity feedback training-tomographic neurofeedback.
AB  - Along with the development of distributed EEG source modeling methods, basic
      approaches to local brain activity (LBA-) neurofeedback (NF) have been suggested.
      Meanwhile several attempts using LORETA and sLORETA have been published. This
      article specifically reports on "EEG-based LBA-feedback training" developed by
      Bauer et al. (2011). Local brain activity-feedback has the advantage over other
      sLORETA-based approaches in the way that feedback is exclusively controlled by
      EEG-generating sources within a selected cortical region of training (ROT):
      feedback is suspended if there is no source. In this way the influence of sources
      in the vicinity of the ROT is excluded. First applications have yielded promising
      results: aiming to enhance activity in left hemispheric linguistic areas, five
      experimental subjects increased significantly the feedback rate whereas five
      controls receiving sham feedback did not, both after 13 training runs (U-test, p
      < 0.01). Preliminary results of another study that aims to document effects of
      LBA-feedback training of the Anterior Cingulate Cortex (ACC) and Dorso-Lateral
      Prefrontal Cortex (DLPFC) by fMRI revealed more local ACC-activity after
      successful training (Radke et al., 2014). 

PMID- 25566029
TI  - Detection of mental imagery and attempted movements in patients with disorders of
      consciousness using EEG.
AB  - Further development of an EEG based communication device for patients with
      disorders of consciousness (DoC) could benefit from addressing the following gaps
      in knowledge-first, an evaluation of different types of motor imagery; second, an
      evaluation of passive feet movement as a mean of an initial classifier setup; and
      third, rapid delivery of biased feedback. To that end we investigated whether
      complex and/or familiar mental imagery, passive, and attempted feet movement can
      be reliably detected in patients with DoC using EEG recordings, aiming to provide
      them with a means of communication. Six patients in a minimally conscious state
      (MCS) took part in this study. The patients were verbally instructed to perform
      different mental imagery tasks (sport, navigation), as well as attempted feet
      movements, to induce distinctive event-related (de)synchronization (ERD/S)
      patterns in the EEG. Offline classification accuracies above chance level were
      reached in all three tasks (i.e., attempted feet, sport, and navigation), with
      motor tasks yielding significant (p < 0.05) results more often than navigation
      (sport: 10 out of 18 sessions; attempted feet: 7 out of 14 sessions; navigation:
      4 out of 12 sessions). The passive feet movements, evaluated in one patient,
      yielded mixed results: whereas time-frequency analysis revealed task-related EEG
      changes over neurophysiological plausible cortical areas, the classification
      results were not significant enough (p < 0.05) to setup an initial classifier for
      the detection of attempted movements. Concluding, the results presented in this
      study are consistent with the current state of the art in similar studies, to
      which we contributed by comparing different types of mental tasks, notably
      complex motor imagery and attempted feet movements, within patients. Furthermore,
      we explored new venues, such as an evaluation of passive feet movement as a mean
      of an initial classifier setup, and rapid delivery of biased feedback. 

PMID- 25566031
TI  - How do selective attentional processes contribute to maintenance and recall in
      children's working memory capacity?
AB  - The development of working memory capacity is considered from the perspective of
      the active maintenance of items in primary memory (PM) and a cue-dependent search
      component, secondary memory (SM). Using free recall, plus a more novel serial
      interleaved items task, age-related increases in PM estimates were evident in
      both paradigms. In addition to this, age-related improvements in attentional
      selectivity were observed, indexed by the recall of target and non-target
      information respectively. To further characterize PM, presentation modality was
      varied in the serial interleaved items task (auditory, visual and dual
      presentation). Developmental differences were found in the effectiveness of
      presentation formats. Older children's recall was enhanced by the combination of
      labeled visual items and enduring auditory information, whilst the same format
      was detrimental to younger children's recall of target information. The present
      results show how estimates of PM and SM in children relate to the development of
      working memory capacity, but measurement of these constructs in children is not
      straightforward. Data also points to age-related changes in selective attention,
      which in turn contributes to children's ability to process and maintain
      information in working memory. 

PMID- 25566028
TI  - Tuning pathological brain oscillations with neurofeedback: a systems neuroscience
      framework.
AB  - Neurofeedback (NFB) is emerging as a promising technique that enables self
      regulation of ongoing brain oscillations. However, despite a rise in empirical
      evidence attesting to its clinical benefits, a solid theoretical basis is still
      lacking on the manner in which NFB is able to achieve these outcomes. The present
      work attempts to bring together various concepts from neurobiology, engineering,
      and dynamical systems so as to propose a contemporary theoretical framework for
      the mechanistic effects of NFB. The objective is to provide a firmly
      neurophysiological account of NFB, which goes beyond traditional behaviorist
      interpretations that attempt to explain psychological processes solely from a
      descriptive standpoint whilst treating the brain as a "black box". To this end,
      we interlink evidence from experimental findings that encompass a broad range of
      intrinsic brain phenomena: starting from "bottom-up" mechanisms of neural
      synchronization, followed by "top-down" regulation of internal brain states,
      moving to dynamical systems plus control-theoretic principles, and concluding
      with activity-dependent as well as homeostatic forms of brain plasticity. In
      support of our framework, we examine the effects of NFB in several brain
      disorders, including attention-deficit hyperactivity (ADHD) and post-traumatic
      stress disorder (PTSD). In sum, it is argued that pathological oscillations
      emerge from an abnormal formation of brain-state attractor landscape(s). The
      central thesis put forward is that NFB tunes brain oscillations toward a
      homeostatic set-point which affords an optimal balance between network
      flexibility and stability (i.e., self-organised criticality (SOC)). 

PMID- 25566033
TI  - Neural correlates of causal power judgments.
AB  - Causal inference is a fundamental component of cognition and perception.
      Probabilistic theories of causal judgment (most notably causal Bayes networks)
      derive causal judgments using metrics that integrate contingency information. But
      human estimates typically diverge from these normative predictions. This is
      because human causal power judgments are typically strongly influenced by beliefs
      concerning underlying causal mechanisms, and because of the way knowledge is
      retrieved from human memory during the judgment process. Neuroimaging studies
      indicate that the brain distinguishes causal events from mere covariation, and
      also distinguishes between perceived and inferred causality. Areas involved in
      error prediction are also activated, implying automatic activation of possible
      exception cases during causal decision-making. 

PMID- 25566032
TI  - Increased functional connectivity in intrinsic neural networks in individuals
      with aniridia.
AB  - Mutations affecting the PAX6 gene result in aniridia, a condition characterized
      by the lack of an iris and other panocular defects. Among humans with aniridia,
      structural abnormalities also have been reported within the brain. The current
      study examined the functional implications of these deficits through "resting
      state" or task-free functional magnetic resonance imaging (fMRI) in 12
      individuals with aniridia and 12 healthy age- and gender-matched controls. Using
      independent components analysis (ICA) and dual regression, individual patterns of
      functional connectivity associated with three intrinsic connectivity networks
      (ICNs; executive control, primary visual, and default mode) were compared across
      groups. In all three analyses, the aniridia group exhibited regions of greater
      connectivity correlated with the network, while the controls did not show any
      such regions. These differences suggest that individuals with aniridia recruit
      additional neural regions to supplement function in critical intrinsic networks,
      possibly due to inherent structural or sensory abnormalities related to the
      disorder. 

PMID- 25566034
TI  - Differential effects of theta/beta and SMR neurofeedback in ADHD on sleep onset
      latency.
AB  - Recent studies suggest a role for sleep and sleep problems in the etiology of
      attention deficit hyperactivity disorder (ADHD) and a recent model about the
      working mechanism of sensori-motor rhythm (SMR) neurofeedback, proposed that this
      intervention normalizes sleep and thus improves ADHD symptoms such as inattention
      and hyperactivity/impulsivity. In this study we compared adult ADHD patients (N =
      19) to a control group (N = 28) and investigated if differences existed in sleep
      parameters such as Sleep Onset Latency (SOL), Sleep Duration (DUR) and overall
      reported sleep problems (PSQI) and if there is an association between sleep
      parameters and ADHD symptoms. Secondly, in 37 ADHD patients we investigated the
      effects of SMR and Theta/Beta (TBR) neurofeedback on ADHD symptoms and sleep
      parameters and if these sleep parameters may mediate treatment outcome to SMR and
      TBR neurofeedback. In this study we found a clear continuous relationship between
      self-reported sleep problems (PSQI) and inattention in adults with- and without
      ADHD. TBR neurofeedback resulted in a small reduction of SOL, this change in SOL
      did not correlate with the change in ADHD symptoms and the reduction in SOL only
      happened in the last half of treatment, suggesting this is an effect of symptom
      improvement not specifically related to TBR neurofeedback. SMR neurofeedback
      specifically reduced the SOL and PSQI score, and the change in SOL and change in
      PSQI correlated strongly with the change in inattention, and the reduction in SOL
      was achieved in the first half of treatment, suggesting the reduction in SOL
      mediated treatment response to SMR neurofeedback. Clinically, TBR and SMR
      neurofeedback had similar effects on symptom reduction in ADHD (inattention and
      hyperactivity/impulsivity). These results suggest differential effects and
      different working mechanisms for TBR and SMR neurofeedback in the treatment of
      ADHD. 

PMID- 25566035
TI  - Detection of response to command using voluntary control of breathing in
      disorders of consciousness.
AB  - BACKGROUND: Detecting signs of consciousness in patients in a vegetative
      state/unresponsive wakefulness syndrome (UWS/VS) or minimally conscious state
      (MCS) is known to be very challenging. Plotkin et al. (2010) recently showed the
      possibility of using a breathing-controlled communication device in patients with
      locked in syndrome. We here aim to test a breathing-based "sniff controller" that
      could be used as an alternative diagnostic tool to evaluate response to command
      in severely brain damaged patients with chronic disorders of consciousness (DOC).
      METHODS: Twenty-five DOC patients were included. Patients' resting breathing
      amplitude was measured during a 5 min resting condition. Next, they were
      instructed to end the presentation of a music sequence by sniffing vigorously. An
      automated detection of changes in breathing amplitude (i.e., >1.5 SD of resting)
      ended the music and hence provided positive feedback to the patient. RESULTS:
      None of the 11 UWS/VS patients showed a sniff-based response to command. One out
      of 14 patients with MCS was able to willfully modulate his breathing pattern to
      answer the command on 16/19 trials (accuracy 84%). Interestingly, this patient
      failed to show any other motor response to command. DISCUSSION: We here
      illustrate the possible interest of using breathing-dependent response to command
      in the detection of residual cognition in patients with DOC after severe brain
      injury.

PMID- 25566030
TI  - Abnormal asymmetry of brain connectivity in schizophrenia.
AB  - Recently, a growing body of data has revealed that beyond a dysfunction of
      connectivity among different brain areas in schizophrenia patients (SCZ), there
      is also an abnormal asymmetry of functional connectivity compared with healthy
      subjects. The loss of the cerebral torque and the abnormalities of gyrification,
      with an increased or more complex cortical folding in the right hemisphere may
      provide an anatomical basis for such aberrant connectivity in SCZ. Furthermore,
      diffusion tensor imaging studies have shown a significant reduction of leftward
      asymmetry in some key white-matter tracts in SCZ. In this paper, we review the
      studies that investigated both structural brain asymmetry and asymmetry of
      functional connectivity in healthy subjects and SCZ. From an analysis of the
      existing literature on this topic, we can hypothesize an overall generally
      attenuated asymmetry of functional connectivity in SCZ compared to healthy
      controls. Such attenuated asymmetry increases with the duration of the disease
      and correlates with psychotic symptoms. Finally, we hypothesize that structural
      deficits across the corpus callosum may contribute to the abnormal asymmetry of
      intra-hemispheric connectivity in schizophrenia. 

PMID- 25566036
TI  - Adult age differences in prospective memory in the laboratory: are they related
      to higher stress levels in the elderly?
AB  - To explain age deficits found in laboratory-based prospective memory (PM) tasks,
      it has recently been suggested that the testing situation per se may be more
      stressful for older adults, thereby impairing their performance. To test this
      assumption, subjective and physiological stress levels were assessed at several
      times during the experiment in 33 younger and 29 older adults. In addition, half
      of participants were randomized in a condition where they completed a relaxation
      intervention before performing a time-based PM task. Results confirmed the age
      deficit in laboratory PM. Subjective and physiological stress levels showed no
      age difference and no detrimental association with PM. The intervention
      successfully reduced stress levels in both age groups but had no effect on PM or
      the age deficit. In conclusion, data suggest that age deficits usually observed
      in laboratory PM may not be due to higher stress levels in the older adults. 

PMID- 25566038
TI  - No relation between afferent facilitation induced by digital nerve stimulation
      and the latency of cutaneomuscular reflexes and somatosensory evoked magnetic
      fields.
AB  - Primary motor cortex (M1) excitability can be assessed using transcranial
      magnetic stimulation (TMS) and can be modulated by a conditioning electrical
      stimulus delivered to a peripheral nerve prior to TMS. This is known as afferent
      facilitation (AF). The aim of this study was to determine whether AF can be
      induced by digital nerve stimulation and to evaluate the relation between the
      interstimulus interval (ISI) required for AF and the latency of the E2 component
      of the cutaneomuscular reflex (CMR) and the prominent somatosensory evoked field
      (SEF) deflection that occurs approximately 70 ms after digital nerve stimulation
      (P60m). Stimulation of the digital nerve of the right index finger was followed,
      at various time intervals, by single-pulse TMS applied to the contralateral
      hemisphere. The ISI between digital nerve stimulation and TMS was 20, 30, 40, 50,
      60, 70, 80, 100, 140, 180, 200, or 220 ms. Single-pulse TMS was performed alone
      as a control. SEFs were recorded following digital nerve stimulation of the index
      finger, and the equivalent current dipole of prominent deflections that occurred
      around 70 ms after the stimulation was calculated. CMRs were recorded following
      digital nerve stimulation during muscle contraction. Motor evoked potentials
      (MEPs) were facilitated at an ISI between 50 and 100 ms in 11 of 13 subjects, and
      the facilitated MEP amplitude was larger than the unconditioned MEP amplitude (p
      < 0.01). There was no significant correlation between the ISI at which AF was
      maximal and the latency of the P60m component of the SEF (r = -0.50, p = 0.12) or
      the E2 component of the CMR (r = -0.54, p = 0.88). These results indicate that
      the precise ISI required for AF cannot be predicted using SEF or CMR. 

PMID- 25566037
TI  - Frequency-specific network topologies in the resting human brain.
AB  - A community is a set of nodes with dense inter-connections, while there are
      sparse connections between different communities. A hub is a highly connected
      node with high centrality. It has been shown that both "communities" and "hubs"
      exist simultaneously in the brain's functional connectivity network (FCN), as
      estimated by correlations among low-frequency spontaneous fluctuations in
      functional magnetic resonance imaging (fMRI) signal changes (0.01-0.10 Hz). This
      indicates that the brain has a spatial organization that promotes both
      segregation and integration of information. Here, we demonstrate that frequency
      specific network topologies that characterize segregation and integration also
      exist within this frequency range. In investigating the coherence spectrum among
      87 brain regions, we found that two frequency bands, 0.01-0.03 Hz (very low
      frequency [VLF] band) and 0.07-0.09 Hz (low frequency [LF] band), mainly
      contributed to functional connectivity. Comparing graph theoretical indices for
      the VLF and LF bands revealed that the network in the former had a higher
      capacity for information segregation between identified communities than the
      latter. Hubs in the VLF band were mainly located within the anterior cingulate
      cortices, whereas those in the LF band were located in the posterior cingulate
      cortices and thalamus. Thus, depending on the timescale of brain activity, at
      least two distinct network topologies contributed to information segregation and
      integration. This suggests that the brain intrinsically has timescale-dependent
      functional organizations. 

PMID- 25566040
TI  - Interhemispheric synchrony in the neonatal EEG revisited: activation synchrony
      index as a promising classifier.
AB  - A key feature of normal neonatal EEG at term age is interhemispheric synchrony
      (IHS), which refers to the temporal co-incidence of bursting across hemispheres
      during trace alternant EEG activity. The assessment of IHS in both clinical and
      scientific work relies on visual, qualitative EEG assessment without clearly
      quantifiable definitions. A quantitative measure, activation synchrony index
      (ASI), was recently shown to perform well as compared to visual assessments. The
      present study was set out to test whether IHS is stable enough for clinical use,
      and whether it could be an objective feature of EEG normality. We analyzed 31
      neonatal EEG recordings that had been clinically classified as normal (n = 14) or
      abnormal (n = 17) using holistic, conventional visual criteria including
      amplitude, focal differences, qualitative synchrony, and focal abnormalities. We
      selected 20-min epochs of discontinuous background pattern. ASI values were
      computed separately for different channel pair combinations and window lengths to
      define them for the optimal ASI intraindividual stability. Finally, ROC curves
      were computed to find trade-offs related to compromised data lengths, a common
      challenge in neonatal EEG studies. Using the average of four consecutive 2.5-min
      epochs in the centro-occipital bipolar derivations gave ASI estimates that very
      accurately distinguished babies clinically classified as normal vs. abnormal. It
      was even possible to draw a cut-off limit (ASI~3.6) which correctly classified
      the EEGs in 97% of all cases. Finally, we showed that compromising the length of
      EEG segments from 20 to 5 min leads to increased variability in ASI-based
      classification. Our findings support the prior literature that IHS is an
      important feature of normal neonatal brain function. We show that ASI may provide
      diagnostic value even at individual level, which strongly supports its use in
      prospective clinical studies on neonatal EEG as well as in the feature set of
      upcoming EEG classifiers. 

PMID- 25566039
TI  - The neural substrates of natural reading: a comparison of normal and nonword text
      using eyetracking and fMRI.
AB  - Most previous studies investigating the neural correlates of reading have
      presented text using serial visual presentation (SVP), which may not fully
      reflect the underlying processes of natural reading. In the present study, eye
      movements and BOLD data were collected while subjects either read normal
      paragraphs naturally or moved their eyes through "paragraphs" of pseudo-text
      (pronounceable pseudowords or consonant letter strings) in two pseudo-reading
      conditions. Eye movement data established that subjects were reading and scanning
      the stimuli normally. A conjunction fMRI analysis across natural- and pseudo
      reading showed that a common eye-movement network including frontal eye fields
      (FEF), supplementary eye fields (SEF), and intraparietal sulci was activated,
      consistent with previous studies using simpler eye movement tasks. In addition,
      natural reading versus pseudo-reading showed different patterns of brain
      activation: normal reading produced activation in a well-established language
      network that included superior temporal gyrus/sulcus, middle temporal gyrus
      (MTG), angular gyrus (AG), inferior frontal gyrus, and middle frontal gyrus,
      whereas pseudo-reading produced activation in an attentional network that
      included anterior/posterior cingulate and parietal cortex. These results are
      consistent with results found in previous single-saccade eye movement tasks and
      SVP reading studies, suggesting that component processes of eye-movement control
      and language processing observed in past fMRI research generalize to natural
      reading. The results also suggest that combining eyetracking and fMRI is a
      suitable method for investigating the component processes of natural reading in
      fMRI research. 

PMID- 25566041
TI  - How vertical hand movements impact brain activity elicited by literally and
      metaphorically related words: an ERP study of embodied metaphor.
AB  - Embodied metaphor theory suggests abstract concepts are metaphorically linked to
      more experientially basic ones and recruit sensorimotor cortex for their
      comprehension. To test whether words associated with spatial attributes
      reactivate traces in sensorimotor cortex, we recorded EEG from the scalp of
      healthy adults as they read words while performing a concurrent task involving
      either upward- or downward- directed arm movements. ERPs were time-locked to
      words associated with vertical space-either literally (ascend, descend) or
      metaphorically (inspire, defeat)-as participants made vertical movements that
      were either congruent or incongruent with the words. Congruency effects emerged
      200-300 ms after word onset for literal words, but not until after 500 ms post
      onset for metaphorically related words. Results argue against a strong version of
      embodied metaphor theory, but support a role for sensorimotor simulation in
      concrete language. 

PMID- 25566042
TI  - Planning following stroke: a relational complexity approach using the tower of
      london.
AB  - Planning on the 4-disk version of the Tower of London (TOL4) was examined in
      stroke patients and unimpaired controls. Overall TOL4 solution scores indicated
      impaired planning in the frontal stroke but not non-frontal stroke patients.
      Consistent with the claim that processing the relations between current states,
      intermediate states, and goal states is a key process in planning, the domain
      general relational complexity metric was a good indicator of the experienced
      difficulty of TOL4 problems. The relational complexity metric shared variance
      with task-specific metrics of moves to solution and search depth. Frontal stroke
      patients showed impaired planning compared to controls on problems at all three
      complexity levels, but at only two of the three levels of moves to solution,
      search depth and goal ambiguity. Non-frontal stroke patients showed impaired
      planning only on the most difficult quaternary-relational and high search depth
      problems. An independent measure of relational processing (viz., Latin square
      task) predicted TOL4 solution scores after controlling for stroke status and
      location, and executive processing (Trail Making Test). The findings suggest that
      planning involves a domain-general capacity for relational processing that
      depends on the frontal brain regions. 

PMID- 25566043
TI  - Stochastic model predicts evolving preferences in the Iowa gambling task.
AB  - Learning under uncertainty is a common task that people face in their daily life.
      This process relies on the cognitive ability to adjust behavior to environmental
      demands. Although the biological underpinnings of those cognitive processes have
      been extensively studied, there has been little work in formal models seeking to
      capture the fundamental dynamic of learning under uncertainty. In the present
      work, we aimed to understand the basic cognitive mechanisms of outcome processing
      involved in decisions under uncertainty and to evaluate the relevance of previous
      experiences in enhancing learning processes within such uncertain context. We
      propose a formal model that emulates the behavior of people playing a well
      established paradigm (Iowa Gambling Task - IGT) and compare its outcome with a
      behavioral experiment. We further explored whether it was possible to emulate
      maladaptive behavior observed in clinical samples by modifying the model
      parameter which controls the update of expected outcomes distributions. Results
      showed that the performance of the model resembles the observed participant
      performance as well as IGT performance by healthy subjects described in the
      literature. Interestingly, the model converges faster than some subjects on the
      decks with higher net expected outcome. Furthermore, the modified version of the
      model replicated the trend observed in clinical samples performing the task. We
      argue that the basic cognitive component underlying learning under uncertainty
      can be represented as a differential equation that considers the outcomes of
      previous decisions for guiding the agent to an adaptive strategy. 

PMID- 25566046
TI  - SparseyTM: event recognition via deep hierarchical sparse distributed codes.
AB  - The visual cortex's hierarchical, multi-level organization is captured in many
      biologically inspired computational vision models, the general idea being that
      progressively larger scale (spatially/temporally) and more complex visual
      features are represented in progressively higher areas. However, most earlier
      models use localist representations (codes) in each representational field (which
      we equate with the cortical macrocolumn, "mac"), at each level. In localism, each
      represented feature/concept/event (hereinafter "item") is coded by a single unit.
      The model we describe, Sparsey, is hierarchical as well but crucially, it uses
      sparse distributed coding (SDC) in every mac in all levels. In SDC, each
      represented item is coded by a small subset of the mac's units. The SDCs of
      different items can overlap and the size of overlap between items can be used to
      represent their similarity. The difference between localism and SDC is crucial
      because SDC allows the two essential operations of associative memory, storing a
      new item and retrieving the best-matching stored item, to be done in fixed time
      for the life of the model. Since the model's core algorithm, which does both
      storage and retrieval (inference), makes a single pass over all macs on each time
      step, the overall model's storage/retrieval operation is also fixed-time, a
      criterion we consider essential for scalability to the huge ("Big Data")
      problems. A 2010 paper described a nonhierarchical version of this model in the
      context of purely spatial pattern processing. Here, we elaborate a fully
      hierarchical model (arbitrary numbers of levels and macs per level), describing
      novel model principles like progressive critical periods, dynamic modulation of
      principal cells' activation functions based on a mac-level familiarity measure,
      representation of multiple simultaneously active hypotheses, a novel method of
      time warp invariant recognition, and we report results showing
      learning/recognition of spatiotemporal patterns. 

PMID- 25566044
TI  - A conceptual framework of computations in mid-level vision.
AB  - If a picture is worth a thousand words, as an English idiom goes, what should
      those words-or, rather, descriptors-capture? What format of image representation
      would be sufficiently rich if we were to reconstruct the essence of images from
      their descriptors? In this paper, we set out to develop a conceptual framework
      that would be: (i) biologically plausible in order to provide a better
      mechanistic understanding of our visual system; (ii) sufficiently robust to apply
      in practice on realistic images; and (iii) able to tap into underlying structure
      of our visual world. We bring forward three key ideas. First, we argue that
      surface-based representations are constructed based on feature inference from the
      input in the intermediate processing layers of the visual system. Such
      representations are computed in a largely pre-semantic (prior to categorization)
      and pre-attentive manner using multiple cues (orientation, color, polarity,
      variation in orientation, and so on), and explicitly retain configural relations
      between features. The constructed surfaces may be partially overlapping to
      compensate for occlusions and are ordered in depth (figure-ground organization).
      Second, we propose that such intermediate representations could be formed by a
      hierarchical computation of similarity between features in local image patches
      and pooling of highly-similar units, and reestimated via recurrent loops
      according to the task demands. Finally, we suggest to use datasets composed of
      realistically rendered artificial objects and surfaces in order to better
      understand a model's behavior and its limitations. 

PMID- 25566047
TI  - Modeling the influence of short term depression in vesicle release and stochastic
      calcium channel gating on auditory nerve spontaneous firing statistics.
AB  - We propose several modifications to an existing computational model of stochastic
      vesicle release in inner hair cell ribbon synapses, with the aim of producing
      simulated auditory nerve fiber spiking data that more closely matches empirical
      data. Specifically, we studied the inter-spike-interval (ISI) distribution, and
      long and short term ISI correlations in spontaneous spiking in post-synaptic
      auditory nerve fibers. We introduced short term plasticity to the pre-synaptic
      release probability, in a manner analogous to standard stochastic models of
      cortical short term synaptic depression. This modification resulted in a similar
      distribution of vesicle release intervals to that estimated from empirical data.
      We also introduced a biophysical stochastic model of calcium channel opening and
      closing, but showed that this model is insufficient for generating a match with
      empirically observed spike correlations. However, by combining a phenomenological
      model of channel noise and our short term depression model, we generated short
      and long term correlations in auditory nerve spontaneous activity that
      qualitatively match empirical data. 

PMID- 25566048
TI  - Model reduction of strong-weak neurons.
AB  - We consider neurons with large dendritic trees that are weakly excitable in the
      sense that back propagating action potentials are severly attenuated as they
      travel from the small, strongly excitable, spike initiation zone. In previous
      work we have shown that the computational size of weakly excitable cell models
      may be reduced by two or more orders of magnitude, and that the size of strongly
      excitable models may be reduced by at least one order of magnitude, without
      sacrificing the spatio-temporal nature of its inputs (in the sense we reproduce
      the cell's precise mapping of inputs to outputs). We combine the best of these
      two strategies via a predictor-corrector decomposition scheme and achieve a
      drastically reduced highly accurate model of a caricature of the neuron
      responsible for collision detection in the locust. 

PMID- 25566045
TI  - Unsupervised discrimination of patterns in spiking neural networks with
      excitatory and inhibitory synaptic plasticity.
AB  - A spiking neural network model is described for learning to discriminate among
      spatial patterns in an unsupervised manner. The network anatomy consists of
      source neurons that are activated by external inputs, a reservoir that resembles
      a generic cortical layer with an excitatory-inhibitory (EI) network and a sink
      layer of neurons for readout. Synaptic plasticity in the form of STDP is imposed
      on all the excitatory and inhibitory synapses at all times. While long-term
      excitatory STDP enables sparse and efficient learning of the salient features in
      inputs, inhibitory STDP enables this learning to be stable by establishing a
      balance between excitatory and inhibitory currents at each neuron in the network.
      The synaptic weights between source and reservoir neurons form a basis set for
      the input patterns. The neural trajectories generated in the reservoir due to
      input stimulation and lateral connections between reservoir neurons can be
      readout by the sink layer neurons. This activity is used for adaptation of
      synapses between reservoir and sink layer neurons. A new measure called the
      discriminability index (DI) is introduced to compute if the network can
      discriminate between old patterns already presented in an initial training
      session. The DI is also used to compute if the network adapts to new patterns
      without losing its ability to discriminate among old patterns. The final outcome
      is that the network is able to correctly discriminate between all patterns-both
      old and new. This result holds as long as inhibitory synapses employ STDP to
      continuously enable current balance in the network. The results suggest a
      possible direction for future investigation into how spiking neural networks
      could address the stability-plasticity question despite having continuous
      synaptic plasticity. 

PMID- 25566049
TI  - Temporal variability of spectro-temporal receptive fields in the anesthetized
      auditory cortex.
AB  - Temporal variability of neuronal response characteristics during sensory
      stimulation is a ubiquitous phenomenon that may reflect processes such as
      stimulus-driven adaptation, top-down modulation or spontaneous fluctuations. It
      poses a challenge to functional characterization methods such as the receptive
      field, since these often assume stationarity. We propose a novel method for
      estimation of sensory neurons' receptive fields that extends the classic static
      linear receptive field model to the time-varying case. Here, the long-term
      estimate of the static receptive field serves as the mean of a probabilistic
      prior distribution from which the short-term temporally localized receptive field
      may deviate stochastically with time-varying standard deviation. The derived
      corresponding generalized linear model permits robust characterization of
      temporal variability in receptive field structure also for highly non-Gaussian
      stimulus ensembles. We computed and analyzed short-term auditory spectro-temporal
      receptive field (STRF) estimates with characteristic temporal resolution 5-30 s
      based on model simulations and responses from in total 60 single-unit recordings
      in anesthetized Mongolian gerbil auditory midbrain and cortex. Stimulation was
      performed with short (100 ms) overlapping frequency-modulated tones. Results
      demonstrate identification of time-varying STRFs, with obtained predictive model
      likelihoods exceeding those from baseline static STRF estimation. Quantitative
      characterization of STRF variability reveals a higher degree thereof in auditory
      cortex compared to midbrain. Cluster analysis indicates that significant
      deviations from the long-term static STRF are brief, but reliably estimated. We
      hypothesize that the observed variability more likely reflects spontaneous or
      state-dependent internal fluctuations that interact with stimulus-induced
      processing, rather than experimental or stimulus design. 

PMID- 25566050
TI  - Editorial for the research topic: information-based methods for neuroimaging:
      analyzing structure, function and dynamics.

PMID- 25566051
TI  - A low-cost programmable pulse generator for physiology and behavior.
AB  - Precisely timed experimental manipulations of the brain and its sensory
      environment are often employed to reveal principles of brain function. While
      complex and reliable pulse trains for temporal stimulus control can be generated
      with commercial instruments, contemporary options remain expensive and
      proprietary. We have developed Pulse Pal, an open source device that allows users
      to create and trigger software-defined trains of voltage pulses with high
      temporal precision. Here we describe Pulse Pal's circuitry and firmware, and
      characterize its precision and reliability. In addition, we supply online
      documentation with instructions for assembling, testing and installing Pulse Pal.
      While the device can be operated as a stand-alone instrument, we also provide
      application programming interfaces in several programming languages. As an
      inexpensive, flexible and open solution for temporal control, we anticipate that
      Pulse Pal will be used to address a wide range of instrumentation timing
      challenges in neuroscience research. 

PMID- 25566052
TI  - The 'pantie' tumour.
AB  - We present a case of radiation-associated angiosarcoma. A 67-year-old Thai woman
      was diagnosed with endometrium carcinoma stage IC and was treated with surgery
      and radiations. Ten years later, she presented with a gradually enlarging mass on
      the pubic area, in the shape of a pair of panties. Skin biopsy of lesions
      confirmed angiosarcoma. The diagnosis was radiation-associated angiosarcoma. She
      was treated with chemotherapy due to unresectable tumour. The chemotherapy was
      started with paclitaxel 70 mg/m(2) every 2 weeks. After completing the fifth
      cycle of paclitaxel, the lesion was markedly decreased in size and the symptoms
      previously described were also completely resolved. 

PMID- 25566053
TI  - Refractory seborrheic dermatitis of the head in a patient with malignant
      lymphoma.
AB  - Seborrheic dermatitis is an inflammatory eruption that tends to distribute on the
      sebaceous areas of the body and is rarely described as a paraneoplasia. Here we
      report a case with a responsive seborrheic dermatitis-like eruption of the head
      which resulted in generalized erythroderma. Intensive examinations detected
      concurrent malignant lymphoma. 

PMID- 25566054
TI  - (18)F-FDG PET/CT in Patients with Nodular Pulmonary Amyloidosis: Case Report and
      Literature Review.
AB  - A 62-year-old woman was found to have multiple bilateral pulmonary nodules
      showing different (18)F-fluorodeoxyglucose (FDG) uptakes on positron-emission
      tomography/computed tomography (PET/CT). Only the largest nodule in the left
      lower lobe showed an increased (18)F-FDG uptake on PET/CT. Three nodules were
      surgically resected from different lobes of the left lung. Two lobes were benign
      and showed amyloid deposition. The largest nodule in the left lower lobe showed
      adenocarcinoma and a heavy amyloid deposition. Pulmonary amyloidosis should be
      added to the differential diagnosis for cases with multiple pulmonary nodules
      that show different (18)F-FDG uptakes on PET/CT. To the best of our knowledge,
      this is the second reported case of a lung nodule consisting of adenocarcinoma
      and amyloid deposition. 

PMID- 25566055
TI  - Long-term survival in a case of pleomorphic carcinoma with a brain metastasis.
AB  - Pleomorphic carcinoma (PC) is a rare malignant lung tumor with a poorer prognosis
      compared to other histological types of non-small cell lung cancer. However,
      several recent immunohistochemical studies revealed that a low MIB-1 index is a
      good prognostic marker in patients with PC. We report the case of a patient with
      PC and a single brain metastasis that achieved long-term recurrence-free survival
      following treatment with combined modality therapy. In this case, the MIB-1 index
      was reduced by gemcitabine-based chemotherapy, which may have led to long-term
      disease-free survival. The MIB-1 index may be a useful biomarker for the response
      to chemotherapy. 

PMID- 25566056
TI  - Port-site metastasis of mucinous borderline ovarian tumor after laparoscopy.
AB  - We report a case of port-site metastasis after laparoscopic surgery for
      borderline mucinous ovarian tumors (mBOTs) without spillage and review the
      related literature. The patient was a 50-year-old nulligravida who presented with
      abdominal distension. Magnetic resonance imaging showed a 20 * 10-cm multilocular
      mass with various signal intensities. The wall and septa of the mass were neither
      thick nor enhanced. A laparoscopy was performed. An intact left ovarian tumor was
      observed. The weight of the tumor was 1,540 g. The final diagnosis was stage IA
      intestinal-type mBOT, so the patient did not undergo adjuvant therapy. Twenty-six
      months after surgery, the patient presented with a 3 * 5-cm palpable mass on the
      umbilicus. Biopsy of the mass revealed mucinous adenocarcinoma and computed
      tomography showed a 3.5 * 4.0-cm mass at the umbilicus without additional
      metastases. A laparotomy was performed and no metastasis in the peritoneal cavity
      was observed by gross examination. An umbilical mass resection, hysterectomy,
      right salpingo-oophorectomy, appendectomy, and partial omentectomy were
      performed. Hematoxylin and eosin-stained sections of the umbilical mass revealed
      glands of varying size infiltrating the stroma, immunohistologic staining for
      cytokeratin 7 was positive, and cytokeratin 20 was negative, but no other
      metastases were observed. The patient was diagnosed with port-site metastasis and
      invasive recurrence of mBOT. She underwent six cycles of adjuvant paclitaxel and
      carboplatin therapy. Large ovarian tumors should be carefully extracted without
      spillage of the tumor contents to prevent port-site metastasis, despite the low
      incidence. 

PMID- 25566057
TI  - GAD Antibody-Associated Late-Onset Cerebellar Ataxia in Two Female Siblings.
AB  - BACKGROUND: Anti-glutamic acid decarboxylase antibody (GAD-ab)-associated
      cerebellar ataxia is a rare neurological disorder characterized by cerebellar
      symptoms concomitant with high GAD-ab levels in serum and cerebrospinal fluid
      (CSF). CASE REPORT: We report on 2 female siblings (aged 74 and 76 years)
      presenting with gradual progression of rotational vertigo, gait ataxia and
      vertical diplopia, continuously progressing for 6 months and 6 years,
      respectively. Autoimmune laboratory examinations showed remarkably increased
      serum and CSF GAD-ab levels. Their medical histories revealed late-onset type 1
      diabetes mellitus (T1DM) and other concomitant autoimmune disorders (Grave's
      disease, Hashimoto's thyroiditis). Cerebral MRI and laboratory examinations were
      unremarkable. The diagnosis of GAD-ab-associated cerebellar ataxia with
      particular brainstem involvement was established in both women. After the
      exclusion of an underlying malignancy, immunosuppressive therapy has been
      initiated in both patients, which resulted in stabilization in one and in
      clinical improvement in the other patient. DISCUSSION: The unique association of
      autoantibody-mediated cerebellar ataxia and late-onset T1DM in 2 siblings with
      similar clinical and paraclinical phenotypes strengthens the concept that
      hereditary factors might play a relevant role also in autoimmune diseases so far
      considered to be sporadic. Moreover, the occurrence of continuous vertical
      diplopia broadens the clinical spectrum of GAD-ab-associated neurological
      syndromes.

PMID- 25566058
TI  - Stroke as the First Clinical Manifestation of Takayasu's Arteritis.
AB  - Takayasu's arteritis is a chronic inflammatory disease, and neurological symptoms
      occur in 50% of cases, most commonly including headache, dizziness, visual
      disturbances, convulsive crisis, transient ischemic attack, stroke and posterior
      reversible encephalopathy syndrome. The aim of this study was to report the case
      of a young Brazilian female with a focal neurological deficit. She presented with
      asymmetry of brachial and radial pulses, aphasia, dysarthria and right
      hemiplegia. Stroke was investigated extensively in this young patient. Only
      nonspecific inflammatory markers such as velocity of hemosedimentation and C
      reactive protein were elevated. During hospitalization, clinical treatment was
      performed with pulse therapy showing improvement in neurological recuperation on
      subsequent days. In the chronic phase, the patient was submitted to medicated
      angioplasty of the brachiocephalic trunk with paclitaxel, with significant
      improvement of the stenosis. At the 6-month follow-up, the neurological exam
      presented mild dysarthria, faciobrachial predominant disproportionate
      hemiparesis, an NIHSS score of 4 and a modified Rankin Scale score of 3 (moderate
      incapacity). In conclusion, Takayasu's arteritis must be recognized as a
      potential cause of ischemic stroke in young females. 

PMID- 25566059
TI  - Akinetic crisis in Parkinson's disease is associated with a severe loss of
      striatal dopamine transporter function: a report of two cases.
AB  - Akinetic crisis or acute akinesia is a life-threatening complication of
      Parkinson's disease (PD) with unknown pathophysiological mechanisms. Clinically,
      it resembles the neuroleptic malignant syndrome, and dopaminergic drugs are
      transiently ineffective in the acute phase of the condition. There are no
      published dopaminergic functional imaging studies on PD patients with akinetic
      crisis. Here we report 2 advanced PD patients with akinetic crisis who were
      scanned with SPECT using brain dopamine transporter ligand [(123)I]FP-CIT. The
      first patient was additionally scanned before the condition developed, and the
      second patient was scanned after recovery. Striatal dopamine transporter binding
      was lower during than before the crisis, and both patients showed a nearly
      complete loss of dopamine transporter binding during the crisis. Serial imaging
      showed that the uptake remained negligible despite an improvement in motor
      function after recovery. Akinetic crisis in PD appears to be associated with a
      particularly severe loss of presynaptic striatal dopamine function that does not
      improve after recovery. Apart from presynaptic dopaminergic function, other
      dopaminergic or nondopaminergic mechanisms are involved in the clinical
      improvement of motor functions after akinetic crisis in PD. 

PMID- 25566060
TI  - Successful treatment of retinal angiomatous proliferation with intravitreal
      triamcinolone and ranibizumab injections in a 67-year-old male.
AB  - A 67-year-old male who presented to the eye casualty department with
      deterioration in his vision was diagnosed with retinal angiomatous proliferation.
      After initial deterioration with ranibizumab intravitreal injections, we have
      demonstrated successful treatment and stabilised vision with ranibizumab and a
      single intravitreal triamcinolone injection. Stringent follow-up and top-up
      ranibizumab injections have stabilised his vision and have shown foveal
      improvement on optical coherence tomography imaging. 

PMID- 25566061
TI  - Atypical presentation of antiphospholipid syndrome: a case report.
AB  - We report an atypical presentation of Antiphospholipid syndrome (APS) with
      concomitant subhyaloid hemorrhage, engorged and tortuous retinal veins,
      intraretinal hemorrhages, and cotton wool spots in a 38-year-old female. Medical
      treatment was preferred to any invasive treatment. The subhyaloid hemorrhage
      resolved spontaneously and the patient recovered a visual acuity of 20/20 in her
      right eye 3 months after the initial episode. A prompt diagnosis of this
      condition is fundamental to consider a systemic treatment to avoid any further
      thrombosis. 

PMID- 25566062
TI  - A Female Patient with Down Syndrome and Low-Penetrance Leber's Hereditary Optic
      Neuropathy.
AB  - We present the case of a 19-year-old female with a history of Down syndrome (DS)
      who was referred to our neuro-ophthalmology clinic for evaluation of Leber's
      hereditary optic neuropathy (LHON). The patient's family history was significant
      for a known G11778A mutation in a maternal relative, consistent with LHON. The
      patient was also positive for the G11778A mutation; however, the genotype
      demonstrated low penetrance in the pedigree, with only 1 out of 10 adult male
      offspring showing signs or symptoms of the disease. Mitochondrial mutations
      implicated in LHON have been shown to impair complex I of the electron transport
      chain and thereby reducing the effective generation of adenosine triphosphate and
      increasing the production of toxic reactive oxygen species. Although the partial
      or complete triplicate of chromosome 21 constitutes the etiology of DS, some of
      the pleiotropic phenotypes of the syndrome have been attributed to oxidative
      stress and mitochondrial dysfunction. Given the low penetrance of the mutation
      and the patient's sex, this case illustrates the possibility that the
      mitochondrial mutation demonstrated increased penetrance due to pre-existing
      mitochondrial dysfunction related to DS. 

PMID- 25566063
TI  - Changes in the retinal vascular network morphology (diameter and tortuosity)
      after administration of intravitreal bevacizumab in a patient with ischaemic
      branch retinal vein occlusion.
AB  - We report a case of transient reduction in the diameter and tortuosity of an
      occluded vessel after intravitreal administration of 1.25 mg (0.05 ml)
      bevacizumab in a patient with ischaemic branch retinal vein occlusion. A 64-year
      old hypertensive female presented with chief complaints of reduced vision in her
      right eye for 3 months. Her vision in the right eye was evaluated as counting
      fingers at 2 m. Fundus examination revealed superotemporal branch retinal vein
      occlusion. On fluorescein angiography, in the superotemporal quadrant, there was
      hyperfluorescence that increased in size and intensity in the late phase,
      suggestive of a leaking neovascular frond. In addition, there was capillary non
      perfusion in the adjacent area. The patient was administered 1.25 mg (0.05 ml) of
      bevacizumab intravitreally in her right eye, under all aseptic precautions. After
      1 week, her right eye fundus showed regression of neovascularisation. Fluorescein
      angiography also demonstrated regression of neovascularisation in addition to a
      decrease in the diameter and tortuosity of the retinal vessel. 

PMID- 25566064
TI  - Local Treatment with Triamcinolone Acetonide and Bevacizumab for Ocular Symptoms
      in a Patient with POEMS Syndrome.
AB  - PURPOSE: To report our experience in managing a case of bilateral optic disc
      oedema and unilateral cystoid macular oedema with a posterior subtenon (PST)
      injection of triamcinolone acetonide and intravitreal bevacizumab (IVB) in a
      patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy,
      and skin changes (POEMS) syndrome. CASE REPORT: A 50-year-old healthy woman
      complaining of bilateral blurred vision for several days was referred to the
      ophthalmologist. An eye examination showed a bilateral optic disc swelling and
      small preretinal haemorrhages. In addition, a peripheral neuropathy was found.
      Laboratory tests showed elevated levels of M-protein type IgA of 1.4 g/l and a
      vascular endothelial growth factor (VEGF) concentration of 6.1 ng/ml. The
      cerebrospinal fluid protein content was 131 mg/dl. An abdominal CT scan revealed
      hepatosplenomegaly. The diagnosis of POEMS syndrome was made based on the
      polyneuropathy, hepatosplenomegaly, IgA lambda monoclonal proteinemia, and optic
      disc swelling. As vision declined, 40 mg PST injection of triamcinolone was given
      bilaterally. Ten weeks thereafter, 2 IVB injections of 2.5 mg were administered
      to the left eye, with a 4-week interval. Because of an incomplete recovery of her
      visual functions, diarrhoea and general malaise, melphalan, followed by
      autologous peripheral blood stem cell transplantation, was initiated. After
      systemic treatment, she had no visual complaints anymore, the optic disc oedema
      had resolved, and the VEGF serum concentration had normalized. DISCUSSION: Local
      treatment with IVB and PST injection of triamcinolone can be an option for ocular
      symptoms in POEMS syndrome. However, given the incomplete recovery of the ocular
      abnormalities and the other symptoms, systemic treatment remains standard.

PMID- 25566065
TI  - Multifocal Corneal Excimer Femtosecond Laser in situ Keratomileusis following
      Radial Keratotomy: A Case Report with Six Months of Follow-Up.
AB  - We report the case of a 46-year-old female patient who was referred to our clinic
      (Orasis Eye Clinic, Reinach, Switzerland) seeking improvement of her distance and
      near visual acuity. Radial keratotomy (RK) was performed at a younger age on both
      eyes to correct -5 D myopia. The patient underwent a bilateral same-session
      multifocal corneal excimer femtosecond laser (Supracor) keratomileusis
      correction. We introduce a new correction approach, possibly suitable for
      presbyopic patients previously treated with RK, and we present several potential
      novel advantages such as enhanced near, intermediate vision, and improvement in
      quality of life. This is the first report of a bilateral excimer laser treatment
      attempt of presbyopia following RK. 

PMID- 25566066
TI  - Differential expression of sirtuin family members in the developing, adult, and
      aged rat brain.
AB  - The sirtuins are NAD(+)-dependent protein deacetylases and/or ADP
      ribosyltransferases that play roles in metabolic homeostasis, stress response and
      potentially aging. This enzyme family resides in different subcellular
      compartments, and acts on a number of different targets in the nucleus, cytoplasm
      and in the mitochondria. Despite their recognized ability to regulate metabolic
      processes, the roles played by specific sirtuins in the brain-the most energy
      demanding tissue in the body-remains less well investigated and understood. In
      the present study, we examined the regional mRNA and protein expression patterns
      of individual sirtuin family members in the developing, adult, and aged rat
      brain. Our results show that while each sirtuin is expressed in the brain at each
      of these different stages, they display unique spatial and temporal expression
      patterns within the brain. Further, for specific members of the family, the
      protein expression profile did not coincide with their respective mRNA expression
      profile. Moreover, using primary cultures enriched for neurons and astrocytes
      respectively, we found that specific sirtuin members display preferential neural
      lineage expression. Collectively, these results provide the first composite
      illustration that sirtuin family members display differential expression patterns
      in the brain, and provide evidence that specific sirtuins could potentially be
      targeted to achieve cell-type selective effects within the brain. 

PMID- 25566068
TI  - Ankle muscle strength discriminates fallers from non-fallers.
AB  - It is well known that center of pressure (CoP) displacement correlates negatively
      with the maximal isometric torque (MIT) of ankle muscles. This relationship has
      never been investigated in elderly fallers (EF). The purpose of this study was
      thus to analyze the relationship between the MIT of ankle muscles and CoP
      displacement in upright stance in a sample aged between 18 and 90 years old that
      included EF. The aim was to identify a threshold of torque below which balance is
      compromised. The MIT of Plantar flexors (PFs) and dorsal flexors (DFs) and CoP
      were measured in 90 volunteers: 21 healthy young adults (YA) (age: 24.1 +/- 5.0),
      12 healthy middle-aged adults (MAA) (age: 50.2 +/- 4.5), 27 healthy elderly non
      fallers (ENF) (age: 75.5 +/- 7.0) and 30 EF (age: 78.8 +/- 6.7). The MIT of PF
      and DF were summed to obtain the overall maximal ankle muscle strength. Body
      weight and height were used to normalize MIT (nMIT) and CoP (nCoP), respectively.
      nCoP correlated negatively with nMIT. 90% of EF generated an nMIT <3.1 N.m.kg(
      1), whereas 85% of non-fallers generated an nMIT >3.1 N.m.kg(-1). The
      relationship between nMIT and nCoP implies that ankle muscle weakness contributes
      to increased postural instability and the risk of falling. We observed that below
      the threshold of 3.1 N.m.kg(-1), postural stability was dramatically diminished
      and balance was compromised. Our results suggest that measuring ankle torque
      could be used in routine clinical practice to identify potential fallers. 

PMID- 25566067
TI  - Feasibility of resistance training in adult McArdle patients: clinical outcomes
      and muscle strength and mass benefits.
AB  - We analyzed the effects of a 4-month resistance (weight lifting) training program
      followed by a 2-month detraining period in 7 adult McArdle patients (5 female)
      on: muscle mass (assessed by DXA), strength, serum creatine kinase (CK) activity
      and clinical severity. Adherence to training was >=84% in all patients and no
      major contraindication or side effect was noted during the training or strength
      assessment sessions. The training program had a significant impact on total and
      lower extremities' lean mass (P < 0.05 for the time effect), with mean values
      increasing with training by +855 g (95% confidence interval (CI): 30, 1679) and
      +547 g (95%CI: 116, 978), respectively, and significantly decreasing with
      detraining. Body fat showed no significant changes over the study period. Bench
      press and half-squat performance, expressed as the highest value of average
      muscle power (W) or force (N) in the concentric-repetition phase of both tests
      showed a consistent increase over the 4-month training period, and decreased with
      detraining. Yet muscle strength and power detraining values were significantly
      higher than pre-training values, indicating that a training effect was still
      present after detraining. Importantly, all the participants, with no exception,
      showed a clear gain in muscle strength after the 4-month training period, e.g.,
      bench press: +52 W (95% CI: 13, 91); half-squat: +173 W (95% CI: 96, 251). No
      significant time effect (P > 0.05) was noted for baseline or post strength
      assessment values of serum CK activity, which remained essentially within the
      range reported in our laboratory for McArdle patients. All the patients changed
      to a lower severity class with training, such that none of them were in the
      highest disease severity class (3) after the intervention and, as such, they did
      not have fixed muscle weakness after training. Clinical improvements were
      retained, in all but one patient, after detraining, such that after detraining
      all patients were classed as class 1 for disease severity. 

PMID- 25566069
TI  - Effects of enactment in episodic memory: a pilot virtual reality study with young
      and elderly adults.
AB  - None of the previous studies on aging have tested the influence of action with
      respect to the degree of interaction with the environment (active or passive
      navigation) and the source of itinerary choice (self or externally imposed), on
      episodic memory (EM) encoding. The aim of this pilot study was to explore the
      influence of these factors on feature binding (the association between what,
      where, and when) in EM and on the subjective sense of remembering. Navigation in
      a virtual city was performed by 64 young and 64 older adults in one of four modes
      of exploration: (1) passive condition where participants were immersed as
      passengers of a virtual car [no interaction, no itinerary control (IC)], (2) IC
      (the subject chose the itinerary, but did not drive the car), (3) low, or (4)
      high navigation control (the subject just moved the car on rails or drove the car
      with a steering-wheel and a gas pedal on a fixed itinerary, respectively). The
      task was to memorize as many events encountered in the virtual environment as
      possible along with their factual (what), spatial (where), and temporal (when)
      details, and then to perform immediate and delayed memory tests. An age-related
      decline was evidenced for immediate and delayed feature binding. Compared to
      passive and high navigation conditions, and regardless of age-groups, feature
      binding was enhanced by low navigation and IC conditions. The subjective sense of
      remembering was boosted by the IC in older adults. Memory performance following
      high navigation was specifically linked to variability in executive functions.
      The present findings suggest that the decision of the itinerary is beneficial to
      boost EM in aging, although it does not eliminate age-related deficits. Active
      navigation can also enhance EM when it is not too demanding for subjects'
      cognitive resources. 

PMID- 25566070
TI  - Pathogenic mechanisms in centronuclear myopathies.
AB  - Centronuclear myopathies (CNMs) are a genetically heterogeneous group of
      inherited neuromuscular disorders characterized by clinical features of a
      congenital myopathy and abundant central nuclei as the most prominent
      histopathological feature. The most common forms of congenital myopathies with
      central nuclei have been attributed to X-linked recessive mutations in the MTM1
      gene encoding myotubularin ("X-linked myotubular myopathy"), autosomal-dominant
      mutations in the DNM2 gene encoding dynamin-2 and the BIN1 gene encoding
      amphiphysin-2 (also named bridging integrator-1, BIN1, or SH3P9), and autosomal
      recessive mutations in BIN1, the RYR1 gene encoding the skeletal muscle ryanodine
      receptor, and the TTN gene encoding titin. Models to study and rescue the
      affected cellular pathways are now available in yeast, C. elegans, drosophila,
      zebrafish, mouse, and dog. Defects in membrane trafficking have emerged as a key
      pathogenic mechanisms, with aberrant T-tubule formation, abnormalities of triadic
      assembly, and disturbance of the excitation-contraction machinery the main
      downstream effects studied to date. Abnormal autophagy has recently been
      recognized as another important collateral of defective membrane trafficking in
      different genetic forms of CNM, suggesting an intriguing link to primary
      disorders of defective autophagy with overlapping histopathological features. The
      following review will provide an overview of clinical, histopathological, and
      genetic aspects of the CNMs in the context of the key pathogenic mechanism,
      outline unresolved questions, and indicate promising future lines of enquiry. 

PMID- 25566071
TI  - In utero therapy for congenital disorders using amniotic fluid stem cells.
AB  - Congenital diseases are responsible for over a third of all pediatric hospital
      admissions. Advances in prenatal screening and molecular diagnosis have allowed
      the detection of many life-threatening genetic diseases early in gestation. In
      utero transplantation (IUT) with stem cells could cure affected fetuses but so
      far in humans, successful IUT using allogeneic hematopoietic stem cells (HSCs),
      has been limited to fetuses with severe immunologic defects and more recently IUT
      with allogeneic mesenchymal stem cell transplantation, has improved phenotype in
      osteogenesis imperfecta. The options of preemptive treatment of congenital
      diseases in utero by stem cell or gene therapy changes the perspective of
      congenital diseases since it may avoid the need for postnatal treatment and
      reduce future costs. Amniotic fluid stem (AFS) cells have been isolated and
      characterized in human, mice, rodents, rabbit, and sheep and are a potential
      source of cells for therapeutic applications in disorders for treatment
      prenatally or postnatally. Gene transfer to the cells with long-term transgenic
      protein expression is feasible. Recently, pre-clinical autologous transplantation
      of transduced cells has been achieved in fetal sheep using minimally invasive
      ultrasound guided injection techniques. Clinically relevant levels of transgenic
      protein were expressed in the blood of transplanted lambs for at least 6 months.
      The cells have also demonstrated the potential of repair in a range of pre
      clinical disease models such as neurological disorders, tracheal repair, bladder
      injury, and diaphragmatic hernia repair in neonates or adults. These results have
      been encouraging, and bring personalized tissue engineering for prenatal
      treatment of genetic disorders closer to the clinic. 

PMID- 25566072
TI  - Antimicrobial peptides: a new class of antimalarial drugs?
AB  - A range of antimicrobial peptides (AMP) exhibit activity on malaria parasites,
      Plasmodium spp., in their blood or mosquito stages, or both. These peptides
      include a diverse array of both natural and synthetic molecules varying greatly
      in size, charge, hydrophobicity, and secondary structure features. Along with an
      overview of relevant literature reports regarding AMP that display antiplasmodial
      activity, this review makes a few considerations about those molecules as a
      potential new class of antimalarial drugs. 

PMID- 25566073
TI  - Hemophilia A: an ideal disease to correct in utero.
AB  - Hemophilia A (HA) is the most frequent inheritable defect of the coagulation
      proteins. The current standard of care for patients with HA is prophylactic
      factor infusion, which is comprised of regular (2-3 times per week) intravenous
      infusions of recombinant or plasma-derived FVIII to maintain hemostasis. While
      this treatment has greatly increased the quality of life and lengthened the life
      expectancy for many HA patients, its high cost, the need for lifelong infusions,
      and the fact that it is unavailable to roughly 75% of the world's HA patients
      make this type of treatment far from ideal. In addition, this lifesaving therapy
      suffers from a high risk of treatment failure due to immune response to the
      infused FVIII. There is thus a need for novel treatments, such as those using
      stem cells and/or gene therapy, which have the potential to mediate long-term
      correction or permanent cure following a single intervention. In the present
      review, we discuss the clinical feasibility and unique advantages that an in
      utero approach to treating HA could offer, placing special emphasis on a new
      sheep model of HA we have developed and on the use of mesenchymal stromal cells
      (MSC) as cellular vehicles for delivering the FVIII gene. 

PMID- 25566074
TI  - The effect of deficient muscarinic signaling on commonly reported biochemical
      effects in schizophrenia and convergence with genetic susceptibility loci in
      explaining symptom dimensions of psychosis.
AB  - With the advent of DSM 5 criticism has generally centered on a lack of biological
      validity of the diagnostic criteria. Part of the problem in describing a nosology
      of psychosis is the tacit assumption of multiple genetic causes each with an
      incremental loading on the clinical picture that fails to differentiate a clear
      underlying pathophysiology of high impact. The aim of this paper is to
      consolidate a primary theory of deficient muscarinic signaling underlying key
      clinical features of schizophrenia and its regulation by several important
      genetic associations including neuregulin, DISC and dysbindin. Secondary
      reductions in markers for GABAergic function and changes in the levels of
      interneuron calcium binding proteins parvalbumin and calbindin can be attributed
      to dysfunctional muscarinic transduction. A parallel association exists for
      cytokine production. The convergent pathway hypothesis is likewise used to model
      dopaminergic and glutamatergic theories of schizophrenia. The negative symptom
      dimension is correlated with dysfunction of Akt and ERK transduction, a major
      point of convergence. The present paradigm predicts the importance of a recent
      finding of a deletion in a copy number variant of PLCB1 and its potential use if
      replicated, as one of the first testable biological markers differentiating
      schizophrenia from bipolar disorder and further subtyping of schizophrenia into
      deficit and non-deficit. Potential limitations of PLCB1 as a prospective marker
      are also discussed. 

PMID- 25566077
TI  - Deleterious effects of maternal ingestion of cocoa upon fetal ductus arteriosus
      in late pregnancy.
AB  - Cocoa powder has twice more antioxidants than red wine and three times more than
      green tea. Ten percent of its weight is made up of flavonoids. Cocoa has
      antioxidant and anti-inflammatory effects by downregulating cyclooxigenase-2
      receptors expression in the endothelium and enhancing nitric oxide
      bioavailability. There are evidences that while polyphenols ingestion have
      cardioprotective effects in the adult, it may have deleterious effect on the
      fetus if ingested by the mother on the third trimester of pregnancy, causing
      intrauterine fetal ductus arteriosus (DA) constriction. Polyphenols present in
      many foods and their anti-inflammatory and antinociceptive activities have been
      shown to be as or more powerful than those of indomethacin. These effects are
      dependent on the inhibition of modulation of the arachidonic acid and the
      synthesis of prostaglandins, especially E-2, which is responsible for fetal DA
      patency. So, we hypothesized that this same mechanism is responsible for the
      harmful effect of polyphenol-rich foods, such as cocoa, upon the fetal DA after
      maternal intake of such substances in the third trimester of pregnancy, thereby
      rising the perspective of a note of caution for pregnant women diet. 

PMID- 25566078
TI  - Is redox signaling a feasible target for overcoming multidrug resistance in
      cancer chemotherapy?

PMID- 25566079
TI  - Inflammatory and immune responses in the cochlea: potential therapeutic targets
      for sensorineural hearing loss.
AB  - The inner ear was previously assumed to be an "immune-privileged" organ due to
      the existence of its tight junction-based blood-labyrinth barrier. However,
      studies performed during the past decade revealed that the mesenchymal region of
      the cochlea, including its lateral wall, is a common site of inflammation.
      Neutrophils do not enter this region, which is consistent with the old dogma;
      however, bone marrow-derived resident macrophages are always present in the
      spiral ligament of the lateral wall and are activated in response to various
      types of insults, including noise exposure, ischemia, mitochondrial damage, and
      surgical stress. Recent studies have also revealed another type of immune cell,
      called perivascular melanocyte-like macrophages (PVM/Ms), in the stria
      vascularis. These dedicated antigen-presenting cells also control vascular
      contraction and permeability. This review discusses a series of reports regarding
      inflammatory/immune cells in the cochlear lateral wall, the pathways involved in
      cochlear damage and their potential as therapeutic targets. 

PMID- 25566075
TI  - Role of NG2 expressing cells in addiction: a new approach for an old problem.
AB  - Neuron-glial antigen 2 (NG2) is a proteoglycan expressed predominantly in
      oligodendrocyte progenitor cells (OPCs). NG2-expressing OPCs (NG2-OPCs) are self
      renewing cells that are widely distributed in the gray and white matter areas of
      the central nervous system. NG2-OPCs can mature into premyelinating
      oligodendrocytes and myelinating oligodendroglia which serve as the primary
      source of myelin in the brain. This review characterizes NG2-OPCs in brain
      structure and function, conceptualizes the role of NG2-OPCs in brain regions
      associated with negative reinforcement and relapse to drug seeking and discusses
      how NG2-OPCs are regulated by neuromodulators linked to motivational withdrawal.
      We hope to provide the readers with an overview of the role of NG2-OPCs in brain
      structure and function in the context of negative affect state in substance abuse
      disorders and to integrate our current understanding of the physiological
      significance of the NG2-OPCs in the adult brain. 

PMID- 25566076
TI  - Opioid receptor desensitization: mechanisms and its link to tolerance.
AB  - Opioid receptors (OR) are part of the class A of G-protein coupled receptors and
      the target of the opiates, the most powerful analgesic molecules used in clinic.
      During a protracted use, a tolerance to analgesic effect develops resulting in a
      reduction of the effectiveness. So understanding mechanisms of tolerance is a
      great challenge and may help to find new strategies to tackle this side effect.
      This review will summarize receptor-related mechanisms that could underlie
      tolerance especially receptor desensitization. We will focus on the latest data
      obtained on molecular mechanisms involved in opioid receptor desensitization:
      phosphorylation, receptor uncoupling, internalization, and post-endocytic fate of
      the receptor. 

PMID- 25566080
TI  - The sodium-potassium pump is an information processing element in brain
      computation.

PMID- 25566081
TI  - Allosteric modulation of Ras and the PI3K/AKT/mTOR pathway: emerging therapeutic
      opportunities.
AB  - GTPases and kinases are two predominant signaling modules that regulate cell
      fate. Dysregulation of Ras, a GTPase, and the three eponymous kinases that form
      key nodes of the associated phosphatidylinositol 4,5-bisphosphate 3-kinase
      (PI3K)/AKT/mTOR pathway have been implicated in many cancers, including
      pancreatic cancer, a disease noted for its current lack of effective
      therapeutics. The K-Ras isoform of Ras is mutated in over 90% of pancreatic
      ductal adenocarcinomas (PDAC) and there is growing evidence linking aberrant
      PI3K/AKT/mTOR pathway activity to PDAC. Although these observations suggest that
      targeting one of these nodes might lead to more effective treatment options for
      patients with pancreatic and other cancers, the complex regulatory mechanisms and
      the number of sequence-conserved isoforms of these proteins have been viewed as
      significant barriers in drug development. Emerging insights into the allosteric
      regulatory mechanisms of these proteins suggest novel opportunities for
      development of selective allosteric inhibitors with fragment-based drug discovery
      (FBDD) helping make significant inroads. The fact that allosteric inhibitors of
      Ras and AKT are currently in pre-clinical development lends support to this
      approach. In this article, we will focus on the recent advances and merits of
      developing allosteric drugs targeting these two inter-related signaling pathways.

PMID- 25566083
TI  - Optically gated beating-heart imaging.
AB  - The constant motion of the beating heart presents an obstacle to clear optical
      imaging, especially 3D imaging, in small animals where direct optical imaging
      would otherwise be possible. Gating techniques exploit the periodic motion of the
      heart to computationally "freeze" this movement and overcome motion artifacts.
      Optically gated imaging represents a recent development of this, where image
      analysis is used to synchronize acquisition with the heartbeat in a completely
      non-invasive manner. This article will explain the concept of optical gating,
      discuss a range of different implementation strategies and their strengths and
      weaknesses. Finally we will illustrate the usefulness of the technique by
      discussing applications where optical gating has facilitated novel biological
      findings by allowing 3D in vivo imaging of cardiac myocytes in their natural
      environment of the beating heart. 

PMID- 25566085
TI  - Dynamics of propagation of premature impulses in structurally remodeled infarcted
      myocardium: a computational analysis.
AB  - Initiation of cardiac arrhythmias typically follows one or more premature
      impulses either occurring spontaneously or applied externally. In this study, we
      characterize the dynamics of propagation of single (S2) and double premature
      impulses (S3), and the mechanisms of block of premature impulses at structural
      heterogeneities caused by remodeling of gap junctional conductance (Gj) in
      infarcted myocardium. Using a sub-cellular computer model of infarcted tissue, we
      found that |INa,max|, prematurity (coupling interval with the previous impulse),
      and conduction velocity (CV) of premature impulses change dynamically as they
      propagate away from the site of initiation. There are fundamental differences
      between the dynamics of propagation of S2 and S3 premature impulses: for S2
      impulses |INa,max| recovers fast, prematurity decreases and CV increases as
      propagation proceeds; for S3 impulses low values of |INa,max| persist,
      prematurity could increase, and CV could decrease as impulses propagate away from
      the site of initiation. As a consequence it is more likely that S3 impulses block
      at sites of structural heterogeneities causing source/sink mismatch than S2
      impulses block. Whether premature impulses block at Gj heterogeneities or not is
      also determined by the values of Gj (and the space constant lambda) in the
      regions proximal and distal to the heterogeneity: when lambda in the direction of
      propagation increases >40%, premature impulses could block. The maximum slope of
      CV restitution curves for S2 impulses is larger than for S3 impulses. IN
      CONCLUSION: (1) The dynamics of propagation of premature impulses make more
      likely that S3 impulses block at sites of structural heterogeneities than S2
      impulses block; (2) Structural heterogeneities causing an increase in lambda (or
      CV) of >40% could result in block of premature impulses; (3) A decrease in the
      maximum slope of CV restitution curves of propagating premature impulses is
      indicative of an increased potential for block at structural heterogeneities.

PMID- 25566086
TI  - Proteasome inhibition slightly improves cardiac function in mice with
      hypertrophic cardiomyopathy.
AB  - A growing line of evidence indicates a dysfunctional ubiquitin-proteasome system
      (UPS) in cardiac diseases. Anti-hypertrophic effects and improved cardiac
      function have been reported after treatment with proteasome inhibitors in
      experimental models of cardiac hypertrophy. Here we tested whether proteasome
      inhibition could also reverse the disease phenotype in a genetically-modified
      mouse model of hypertrophic cardiomyopathy (HCM), which carries a mutation in
      Mybpc3, encoding the myofilament protein cardiac myosin-binding protein C. At 7
      weeks of age, homozygous mutant mice (KI) have 39% higher left ventricular mass
      to-body-weight ratio and 29% lower fractional area shortening (FAS) than wild
      type (WT) mice. Both groups were treated with epoxomicin (0.5 mg/kg/day) or
      vehicle for 1 week via osmotic minipumps. Epoxomicin inhibited the chymotrypsin
      like activity by ~50% in both groups. All parameters of cardiac hypertrophy
      (including the fetal gene program) were not affected by epoxomicin treatment in
      both groups. In contrast, FAS was 12% and 35% higher in epoxomicin-treated than
      vehicle-treated WT and KI mice, respectively. To identify which genes or pathways
      could be involved in this positive effect, we performed a transcriptome analysis
      in KI and WT neonatal cardiac myocytes, treated or not with the proteasome
      inhibitor MG132 (1 MUM, 24 h). This revealed 103 genes (four-fold difference; 5%
      FDR) which are commonly regulated in both KI and WT cardiac myocytes. Thus, even
      in genetically-modified mice with manifest HCM, proteasome inhibition showed
      beneficial effects, at least with regard to cardiac function. Targeting the UPS
      in cardiac diseases remains therefore a therapeutic option. 

PMID- 25566082
TI  - Adipose tissues and thyroid hormones.
AB  - The maintenance of energy balance is regulated by complex homeostatic mechanisms,
      including those emanating from adipose tissue. The main function of the adipose
      tissue is to store the excess of metabolic energy in the form of fat. The energy
      stored as fat can be mobilized during periods of energy deprivation (hunger,
      fasting, diseases). The adipose tissue has also a homeostatic role regulating
      energy balance and functioning as endocrine organ that secretes substances that
      control body homeostasis. Two adipose tissues have been identified: white and
      brown adipose tissues (WAT and BAT) with different phenotype, function and
      regulation. WAT stores energy, while BAT dissipates energy as heat. Brown and
      white adipocytes have different ontogenetic origin and lineage and specific
      markers of WAT and BAT have been identified. "Brite" or beige adipose tissue has
      been identified in WAT with some properties of BAT. Thyroid hormones exert
      pleiotropic actions, regulating the differentiation process in many tissues
      including the adipose tissue. Adipogenesis gives raise to mature adipocytes and
      is regulated by several transcription factors (c/EBPs, PPARs) that coordinately
      activate specific genes, resulting in the adipocyte phenotype. T3 regulates
      several genes involved in lipid mobilization and storage and in thermogenesis.
      Both WAT and BAT are targets of thyroid hormones, which regulate genes crucial
      for their proper function: lipogenesis, lipolysis, thermogenesis, mitochondrial
      function, transcription factors, the availability of nutrients. T3 acts directly
      through specific TREs in the gene promoters, regulating transcription factors.
      The deiodinases D3, D2, and D1 regulate the availability of T3. D3 is activated
      during proliferation, while D2 is linked to the adipocyte differentiation
      program, providing T3 needed for lipogenesis and thermogenesis. We examine the
      differences between BAT, WAT and brite/beige adipocytes and the process that lead
      to activation of UCP1 in WAT and the presence of BAT in humans and its relevance.

PMID- 25566087
TI  - Satellite cell activity is differentially affected by contraction mode in human
      muscle following a work-matched bout of exercise.
AB  - Optimal repair and adaptation of skeletal muscle is facilitated by resident stem
      cells (satellite cells). To understand how different exercise modes influence
      satellite cell dynamics, we measured satellite cell activity in conjunction with
      markers of muscle damage and inflammation in human skeletal muscle following a
      single work- and intensity-matched bout of eccentric (ECC) or concentric
      contractions (CON). Participants completed a single bout of ECC (n = 7) or CON (n
      = 7) of the knee extensors. A muscle biopsy was obtained before and 24 h after
      exercise. Functional measures and immunohistochemical analyses were used to
      determine the extent of muscle damage and indices of satellite cell activity.
      Cytokine concentrations were measured using a multiplexed magnetic bead assay.
      Isokinetic peak torque decreased following ECC (p < 0.05) but not CON. Greater
      histological staining of the damage marker Xin was observed in muscle samples of
      ECC vs. CON. Tenasin C immunoreactivity increased 15 fold (p < 0.01) following
      ECC and was unchanged following CON. The inflammatory cytokines interferon gamma
      induced protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1) increased
      pre- to post-ECC (4.26 +/- 1.4 vs. 10.49 +/- 5.8 pg/ml, and 3.06 +/- 0.7 vs. 6.25
      +/- 4.6 pg/ml, respectively; p < 0.05). There was no change in any cytokine post
      CON. Satellite cell content increased 27% pre- to post-ECC (0.10 +/- 0.031 vs.
      0.127 +/- 0.041, respectively; p < 0.05). There was no change in satellite cell
      number in CON (0.099 +/- 0.027 vs. 0.102 +/- 0.029, respectively). There was no
      fiber type-specific satellite cell response following either exercise mode. ECC
      but not CON resulted in an increase in MyoD positive nuclei per myofiber pre- to
      post-exercise (p < 0.05), but there was no change in MyoD DNA binding activity in
      either condition. In conclusion, ECC but not CON results in functional and
      histological evidence of muscle damage that is accompanied by increased satellite
      cell activity 24 h post-exercise. 

PMID- 25566089
TI  - Proteomic approaches for the study of tissue specific effects of 3,5,3'-triiodo-L
      thyronine and 3,5-diiodo-L-thyronine in conditions of altered energy metabolism.
AB  - In vertebrates and, specifically, in mammals, energy homeostasis is achieved by
      the integration of metabolic and neuroendocrine signals linked to one another in
      an intricate network hierarchically responding to the tight modulating action of
      hormones among which thyroid hormones (THs) play a central role. At the cellular
      level, 3,5,3'-triiodo-L-thyronine (T3) acts mainly by binding to specific nuclear
      receptors (TRs) but actually it is becoming more and more evident that some T3-
      actions are independent of TRs and that other iodothyronines, such as 3,5-diiodo
      L-thyronine (T2), affect energy metabolism and adiposity. In the postgenomic era,
      clinical and basic biological researches are increasingly benefiting from the
      recently developed new omics approaches including, among the others, proteomics.
      Considering the recognized value of proteins as excellent targets in physiology,
      the functional and simultaneous analysis of the expression level and the cellular
      localization of multiple proteins can actually be considered fundamental in the
      understanding of complex mechanisms such as those involved in thyroid control of
      metabolism. Here, we will discuss new leads (i.e., target proteins and metabolic
      pathways) emerging in applying proteomics to the actions of T3 and T2 in
      conditions of altered energy metabolism in animal tissues having a central role
      in the control of energy balance. 

PMID- 25566090
TI  - Origin and spatiotemporal dynamics of the peroxisomal endomembrane system.

PMID- 25566088
TI  - Neural reflex regulation of systemic inflammation: potential new targets for
      sepsis therapy.
AB  - Sepsis progresses to multiple organ dysfunction due to the uncontrolled release
      of inflammatory mediators, and a growing body of evidence shows that neural
      signals play a significant role in modulating the immune response. Thus, similar
      toall other physiological systems, the immune system is both connected to and
      regulated by the central nervous system. The efferent arc consists of the
      activation of the hypothalamic-pituitary-adrenal axis, sympathetic activation,
      the cholinergic anti-inflammatory reflex, and the local release of physiological
      neuromodulators. Immunosensory activity is centered on the production of pro
      inflammatory cytokines, signals that are conveyed to the brain through different
      pathways. The activation of peripheral sensory nerves, i.e., vagal paraganglia by
      the vagus nerve, and carotid body (CB) chemoreceptors by the carotid/sinus nerve
      are broadly discussed here. Despite cytokine receptor expression in vagal
      afferent fibers, pro-inflammatory cytokines have no significant effect on vagus
      nerve activity. Thus, the CB may be the source of immunosensory inputs and
      incoming neural signals and, in fact, sense inflammatory mediators, playing a
      protective role during sepsis. Considering that CB stimulation increases
      sympathetic activity and adrenal glucocorticoids release, the electrical
      stimulation of arterial chemoreceptors may be suitable therapeutic approach for
      regulating systemic inflammation. 

PMID- 25566084
TI  - Passive ventricular remodeling in cardiac disease: focus on heterogeneity.
AB  - Passive ventricular remodeling is defined by the process of molecular ventricular
      adaptation to different forms of cardiac pathophysiology. It includes changes in
      tissue architecture, such as hypertrophy, fiber disarray, alterations in cell
      size and fibrosis. Besides that, it also includes molecular remodeling of gap
      junctions, especially those composed by Connexin43 proteins (Cx43) in the
      ventricles that affect cell-to-cell propagation of the electrical impulse, and
      changes in the sodium channels that modify excitability. All those alterations
      appear mainly in a heterogeneous manner, creating irregular and inhomogeneous
      electrical and mechanical coupling throughout the heart. This can predispose to
      reentry arrhythmias and adds to a further deterioration into heart failure. In
      this review, passive ventricular remodeling is described in Hypertrophic
      Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy
      (ICM), and Arrhythmogenic Cardiomyopathy (ACM), with a main focus on the
      heterogeneity of those alterations mentioned above. 

PMID- 25566092
TI  - Ischemia/reperfusion activates myocardial innate immune response: the key role of
      the toll-like receptor.
AB  - Recent data have indicated that the myocardium may act as an immune organ
      initiating cardiac innate immune response and inflammation. It has been suggested
      that activation of the immune system occurs upon the interaction of damage
      associated molecular patterns (DAMPs) generated and released during ischemic
      damage with pattern recognition receptors (Toll like receptors; TLR) present in
      cardiac cells. Among TLRs, TLR4, and TLR2 are the ones mostly expressed in
      cardiac tissue. Whereas TLR4 has shown to play a detrimental role in myocardial
      ischemia/reperfusion (I/R) injury, the effect elicited by TLR2 activation remains
      controversial. Once activated, TLR signaling may occur via the Myd88- and Trif-
      dependent pathways leading to NFkappaB and IFN-3 activation, respectively, and
      subsequent stimulation of pro-inflammatory and immunomodulatory cytokine gene
      expression. Cytokine release contributes to neutrophils activation, recruitment,
      adhesion and infiltration to the site of cardiac injury further perpetuating the
      inflammatory process. This mini-review will focus on the current knowledge
      regarding the role of the heart in inducing and coordinating the innate
      inflammatory response via the TLR signaling pathway in myocardial I/R injury. 

PMID- 25566091
TI  - Detection of the electromechanical delay and its components during voluntary
      isometric contraction of the quadriceps femoris muscle.
AB  - Electromechanical delay (EMD) was described as a time elapsed between first
      trigger and force output. Various results have been reported based on the
      measurement method with observed inconsistent results when the trigger is
      elicited by voluntary contraction. However, mechanomyographic (MMG) sensor placed
      far away on the skin from the contracting muscle was used to detect muscle fiber
      motion and excitation-contraction (EC) coupling which may give unreliable
      results. On this basis, the purpose of this study was to detect EMD during active
      muscle contraction whilst introducing an ultrafast ultrasound (US) method to
      detect muscle fiber motion from a certain depth of the muscle. Time delays
      between onsets of EMG-MMG, EMG-US, MMG-FORCE, US-FORCE, and EMG-FORCE were
      calculated as 20.5 +/- 4.73, 28.63 +/- 6.31, 19.21 +/- 6.79, 30.52 +/- 8.85, and
      49.73 +/- 6.99 ms, respectively. Intrarater correlation coefficient (ICC) was
      higher than MMG when ultrafast US was used for detecton of the Deltat EMG-US and
      Deltat US-FORCE, ICC values of 0.75 and 0.70, respectively. Synchronization of
      the ultrafast ultrasound with EMG and FORCE sensors can reveal reliable and
      clinically useful results related to the EMD and its components when muscle is
      voluntarily contracted. With ultrafast US, we detect onset from the certain depth
      of the muscle excluding the tissues above the muscle acting as a low-pass filter
      which can lead to inaccurate time detection about the onset of the contracting
      muscle fibers. With this non-invasive technique, understanding of the muscle
      dynamics can be facilitated. 

PMID- 25566093
TI  - Expression pattern of arenicins-the antimicrobial peptides of polychaete
      Arenicola marina.
AB  - Immune responses of invertebrate animals are mediated through innate mechanisms,
      among which production of antimicrobial peptides play an important role. Although
      evolutionary Polychaetes represent an interesting group closely related to a
      putative common ancestor of other coelomates, their immune mechanisms still
      remain scarcely investigated. Previously our group has identified arenicins-new
      antimicrobial peptides of the lugworm Arenicola marina, since then these peptides
      were thoroughly characterized in terms of their structure and inhibitory
      potential. In the present study we addressed the question of the physiological
      functions of arenicins in the lugworm body. Using molecular and
      immunocytochemical methods we demonstrated that arencins are expressed in the
      wide range of the lugworm tissues-coelomocytes, body wall, extravasal tissue and
      the gut. The expression of arenicins is constitutive and does not depend on
      stimulation of various infectious stimuli. Most intensively arenicins are
      produced by mature coelomocytes where they function as killing agents inside the
      phagolysosome. In the gut and the body wall epithelia arenicins are released from
      producing cells via secretion as they are found both inside the epithelial cells
      and in the contents of the cuticle. Collectively our study showed that arenicins
      are found in different body compartments responsible for providing a first line
      of defense against infections, which implies their important role as key
      components of both epithelial and systemic branches of host defense. 

PMID- 25566094
TI  - A multiscale chemo-electro-mechanical skeletal muscle model to analyze muscle
      contraction and force generation for different muscle fiber arrangements.
AB  - The presented chemo-electro-mechanical skeletal muscle model relies on a
      continuum-mechanical formulation describing the muscle's deformation and force
      generation on the macroscopic muscle level. Unlike other three-dimensional
      models, the description of the activation-induced behavior of the mechanical
      model is entirely based on chemo-electro-mechanical principles on the microscopic
      sarcomere level. Yet, the multiscale model reproduces key characteristics of
      skeletal muscles such as experimental force-length and force-velocity data on the
      macroscopic whole muscle level. The paper presents the methodological approaches
      required to obtain such a multiscale model, and demonstrates the feasibility of
      using such a model to analyze differences in the mechanical behavior of parallel
      fibered muscles, in which the muscle fibers either span the entire length of the
      fascicles or terminate intrafascicularly. The presented results reveal that
      muscles, in which the fibers span the entire length of the fascicles, show lower
      peak forces, more dispersed twitches and fusion of twitches at lower stimulation
      frequencies. In detail, the model predicted twitch rise times of 38.2 and 17.2 ms
      for a 12 cm long muscle, in which the fibers span the entire length of the
      fascicles and with twelve fiber compartments in series, respectively. Further,
      the twelve-compartment model predicted peak twitch forces that were 19% higher
      than in the single-compartment model. The analysis of sarcomere lengths during
      fixed-end single twitch contractions at optimal length predicts rather small
      sarcomere length changes. The observed lengths range from 75 to 111% of the
      optimal sarcomere length, which corresponds to a region with maximum filament
      overlap. This result suggests that stability issues resulting from activation
      induced stretches of non-activated sarcomeres are unlikely in muscles with
      passive forces appearing at short muscle length. 

PMID- 25566095
TI  - beta3-adrenoceptors inhibit stimulated norepinephrine release in spontaneously
      hypertensive rats.
AB  - Here, the influence of beta3-adrenoceptors on catecholamine release in
      normotensive and spontaneously hypertensive rats was analyzed. Blood pressure was
      recorded through a femoral artery catheter, and cardiac output by ascending aorta
      flow. Time from onset of flow to maximum rise in flow indicated inotropy. Total
      peripheral vascular resistance (TPR) was calculated. Norepinephrine release was
      stimulated with tyramine, which allowed presynaptic release-control to be
      reflected as changes in the plasma norepinephrine concentration. beta3
      adrenoceptor agonist (BRL37344) reduced baseline vascular resistance, the
      tyramine-stimulated norepinephrine overflow and the positive inotropic response
      to tyramine in hypertensive but not normotensive rats. beta3-adrenoceptor
      antagonist (SR59230A) reduced tyramine-stimulated norepinephrine release in both
      strains and the secretion of epinephrine in hypertensive rats. SR59230A reduced
      tyramine-induced tachycardia in normotensive rats, and prevented down-regulation
      of the tyramine-induced rise in resistance in hypertensive rats. It was concluded
      that the contradicting results obtained by agonist vs. antagonist, could be
      explained by their interaction with two different beta-adrenoceptors: The
      BRL37344-dependent inhibition of stimulated norepinephrine release and positive
      inotropic response to tyramine was compatible with stimulation of beta3
      adrenoceptor coupling to inhibitory G-protein. This was observed only in
      hypertensive rats during stimulated, high levels of circulating catecholamines.
      The effect of BRL37344 on baseline vascular resistance was compatible with
      activation of beta3-adrenoceptor coupling to endothelial nitric oxide synthase.
      The inhibitory effect of SR59230A on tyramine-stimulated norepinephrine release
      in both strains, the increased TPR-response to tyramine in hypertensive rats and
      tachycardia in normotensive rats may result from inhibition of the low-affinity
      state beta1-adrenoceptor, also known as the putative beta4-adrenoceptor. 

PMID- 25566096
TI  - Mitochondria dysfunction in lung cancer-induced muscle wasting in C2C12 myotubes.
AB  - AIMS: Cancer cachexia is a syndrome which results in severe loss of muscle mass
      and marked fatigue. Conditioned media from cachexia-inducing cancer cells
      triggers metabolic dysfunction in skeletal muscle, including decreased
      mitochondrial respiration, which may contribute to fatigue. We hypothesized that
      Lewis lung carcinoma conditioned medium (LCM) would impair the mitochondrial
      electron transport chain (ETC) and increase production of reactive oxygen
      species, ultimately leading to decreased mitochondrial respiration. We incubated
      C2C12 myotubes with LCM for 30 min, 2, 4, 24 or 48 h. We measured protein content
      by western blot; oxidant production by 2',7'-dichlorofluorescin diacetate (DCF),
      4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF), and MitoSox;
      cytochrome c oxidase activity by oxidation of cytochrome c substrate; and oxygen
      consumption rate (OCR) of intact myotubes by Seahorse XF Analyzer. RESULTS: LCM
      treatment for 2 or 24 h decreased basal OCR and ATP-related OCR, but did not
      alter the content of mitochondrial complexes I, III, IV and V. LCM treatment
      caused a transient rise in reactive oxygen species (ROS). In particular,
      mitochondrial superoxide (MitoSOX) was elevated at 2 h. 4-Hydroxynonenal, a
      marker of oxidative stress, was elevated in both cytosolic and mitochondrial
      fractions of cell lysates after LCM treatment. CONCLUSION: These data show that
      lung cancer-conditioned media alters electron flow in the ETC and increases
      mitochondrial ROS production, both of which may ultimately impair aerobic
      metabolism and decrease muscle endurance.

PMID- 25566097
TI  - Dietary glucose regulates yeast consumption in adult Drosophila males.
AB  - The adjustment of feeding behavior in response to hunger and satiety contributes
      to homeostatic regulation in animals. The fruit fly Drosophila melanogaster feeds
      on yeasts growing on overripe fruit, providing nutrients required for adult
      survival, reproduction and larval growth. Here, we present data on how the
      nutritional value of food affects subsequent yeast consumption in Drosophila
      adult males. After a period of starvation, flies showed intensive yeast
      consumption. In comparison, flies stopped feeding after having access to a
      nutritive cornmeal diet. Interestingly, dietary glucose was equally efficient as
      the complex cornmeal diet. In contrast, flies fed with sucralose, a non
      metabolizable sweetener, behaved as if they were starved. The adipokinetic
      hormone and insulin-like peptides regulate metabolic processes in insects. We did
      not find any effect of the adipokinetic hormone pathway on this modulation.
      Instead, the insulin pathway was involved in these changes. Flies lacking the
      insulin receptor (InR) did not respond to nutrient deprivation by increasing
      yeast consumption. Together these results show the importance of insulin in the
      regulation of yeast consumption in response to starvation in adult D.
      melanogaster males. 

PMID- 25566098
TI  - Is isolated systolic hypertension an indication for renal denervation?

PMID- 25566099
TI  - Service user- and carer-reported measures of involvement in mental health care
      planning: methodological quality and acceptability to users.
AB  - BACKGROUND: Increasing service user and carer involvement in mental health care
      planning is a key healthcare priority but one that is difficult to achieve in
      practice. To better understand and measure user and carer involvement, it is
      crucial to have measurement questionnaires that are both psychometrically robust
      and acceptable to the end user. METHODS: We conducted a systematic review using
      the terms "care plan$," "mental health," "user perspective$," and "user
      participation" and their linguistic variants as search terms. Databases were
      searched from inception to November 2012, with an update search at the end of
      September 2014. We included any articles that described the development,
      validation or use of a user and/or carer-reported outcome measures of involvement
      in mental health care planning. We assessed the psychometric quality of each
      instrument using the "Evaluating the Measurement of Patient-Reported Outcomes"
      (EMPRO) criteria. Acceptability of each instrument was assessed using novel
      criteria developed in consultation with a mental health service user and carer
      consultation group. RESULTS: We identified eleven papers describing the use,
      development, and/or validation of nine user/carer-reported outcome measures.
      Psychometric properties were sparsely reported and the questionnaires met few
      service user/carer-nominated attributes for acceptability. Where reported, basic
      psychometric statistics were of good quality, indicating that some measures may
      perform well if subjected to more rigorous psychometric tests. The majority were
      deemed to be too long for use in practice. DISCUSSION: Multiple instruments are
      available to measure user/carer involvement in mental health care planning but
      are either of poor quality or poorly described. Existing measures cannot be
      considered psychometrically robust by modern standards, and cannot currently be
      recommended for use. Our review has identified an important knowledge gap, and an
      urgent need to develop new user and carer measures of care-planning involvement.

PMID- 25566101
TI  - Experimental single-session imagery rescripting of distressing memories in
      bowel/bladder-control anxiety: a case series.
AB  - Bowel and bladder obsession [bowel/bladder-control anxiety (BBCA)] is a
      viscerally centered phobic syndrome involving a specific concern about losing
      control of bowel or bladder functioning in a public place. Like other anxiety
      disorders, BBCA is characterized by intrusive imagery. We have previously
      described the nature of intrusive mental imagery in BBCA and found imagery themes
      to be linked to actual experiences of loss of control or to "near misses." A
      causal role for imagery in symptom maintenance can be inferred by examining the
      effects of imagery rescripting. Moreover, successful rescripting may point to a
      potentially efficacious avenue for treatment development. Three cases of imagery
      rescripting are described here with pre-, post-, and follow-up (1-week) data
      reported. After rescripting, two participants experienced pronounced reductions
      in imagery vividness, distress, shame, disgust, and belief conviction. Most
      importantly, all three participants experienced a reduction in fear-associated
      bladder and/or bowel sensations. The results support a causal role for mental
      imagery in bowel-bladder-control anxiety and suggest that rescripting of
      distressing intrusive memories linked to recurrent images may be a useful avenue
      for development of cognitive-behavioral treatments of bladder/bowel-control
      anxiety. 

PMID- 25566102
TI  - Involuntary autobiographical memory chains: implications for autobiographical
      memory organization.

PMID- 25566100
TI  - A review of the role of social cognition in major depressive disorder.
AB  - BACKGROUND: Social cognition - the ability to identify, perceive, and interpret
      socially relevant information - is an important skill that plays a significant
      role in successful interpersonal functioning. Social cognitive performance is
      recognized to be impaired in several psychiatric conditions, but the relationship
      with major depressive disorder is less well understood. The aim of this review is
      to characterize the current understanding of: (i) the different domains of social
      cognition and a possible relationship with major depressive disorder, (ii) the
      clinical presentation of social cognition in acute and remitted depressive
      states, and (iii) the effect of severity of depression on social cognitive
      performance. METHODS: Electronic databases were searched to identify clinical
      studies investigating social cognition in a major depressive disorder population,
      yielding 31 studies for this review. RESULTS: Patients with major depressive
      disorder appear to interpret social cognitive stimuli differently to healthy
      controls: depressed individuals may interpret emotion through a mood-congruent
      bias and have difficulty with cognitive theory of mind tasks requiring
      interpretation of complex mental states. Social cognitive performance appears to
      be inversely associated with severity of depression, whilst the bias toward
      negative emotions persists even in remission. Some deficits may normalize
      following effective pharmacotherapy. CONCLUSIONS: The difficulties with social
      interaction observed in major depressive disorder may, at least in part, be due
      to an altered ability to correctly interpret emotional stimuli and mental states.
      These features seem to persist even in remission, although some may respond to
      intervention. Further research is required in this area to better understand the
      functional impact of these findings and the way in which targeted therapy could
      aid depressed individuals with social interactions.

PMID- 25566104
TI  - Neurological soft signs in the clinical course of schizophrenia: results of a
      meta-analysis.
AB  - Neurological soft signs (NSS) comprise subtle deficits in sensory integration,
      motor coordination, and sequencing of complex motor acts, which are typically
      observed in the majority of schizophrenia patients, including chronic cases and
      neuroleptic-naive first-episode patients. However, recent studies clearly
      demonstrate that NSS are not a static feature of schizophrenia but vary in the
      clinical course of the disorder. This effect was investigated in a meta-analysis
      based on 17 longitudinal studies published between 1992 and 2012. Studies
      included between 10 and 93 patients with schizophrenia spectrum disorders (total
      number 787) with follow-up periods between 2 and 208 weeks. Beside the
      Neurological Examination Scale, the Cambridge Neurological Inventory and the
      Heidelberg NSS Scale were used to assess NSS. All but three studies found NSS to
      decrease in parallel with remission of psychopathological symptoms. This effect
      was more pronounced in patients with a remitting compared to a non-remitting,
      chronic course (Cohen's d 0.81 vs. 0.15) and was significantly correlated with
      length of the follow-up period (r = -0.64) but not with age (r = 0.28). NSS
      scores did not decrease to the level typically observed in healthy controls. From
      a clinical perspective, NSS may therefore be used to identify subjects at risk to
      develop schizophrenia and to monitor disease progression. 

PMID- 25566105
TI  - Distinctiveness and encoding effects in online sentence comprehension.
AB  - In explicit memory recall and recognition tasks, elaboration and contextual
      isolation both facilitate memory performance. Here, we investigate these effects
      in the context of sentence processing: targets for retrieval during online
      sentence processing of English object relative clause constructions differ in the
      amount of elaboration associated with the target noun phrase, or the homogeneity
      of superficial features (text color). Experiment 1 shows that greater elaboration
      for targets during the encoding phase reduces reading times at retrieval sites,
      but elaboration of non-targets has considerably weaker effects. Experiment 2
      illustrates that processing isolated superficial features of target noun phrases
      here, a green word in a sentence with words colored white-does not lead to
      enhanced memory performance, despite triggering longer encoding times. These
      results are interpreted in the light of the memory models of Nairne, 1990, 2001,
      2006, which state that encoding remnants contribute to the set of retrieval cues
      that provide the basis for similarity-based interference effects. 

PMID- 25566103
TI  - An Overview of the Association between Schizotypy and Dopamine.
AB  - Schizotypy refers to a constellation of personality traits that are believed to
      mirror the subclinical expression of schizophrenia in the general population.
      Evidence from pharmacological studies indicates that dopamine (DA) is involved in
      the etiology of schizophrenia. Based on the assumption of a continuum between
      schizophrenia and schizotypy, researchers have begun investigating the
      association between DA and schizotypy using a wide range of methods. In this
      article, we review published studies on this association from the following areas
      of work: (1) experimental investigations of the interactive effects of
      dopaminergic challenges and schizotypy on cognition, motor control, and behavior
      (2), dopaminergically supported cognitive functions (3), studies of associations
      between schizotypy and polymorphisms in genes involved in dopaminergic
      neurotransmission, and (4) molecular imaging studies of the association between
      schizotypy and markers of the DA system. Together, data from these lines of
      evidence suggest that DA is important to the expression and experience of
      schizotypy and associated behavioral biases. An important observation is that the
      experimental designs, methods, and manipulations used in this research are highly
      heterogeneous. Future studies are required to replicate individual observations,
      to enlighten the link between DA and different schizotypy dimensions (positive,
      negative, cognitive disorganization), and to guide the search for solid DA
      sensitive behavioral markers. Such studies are important in order to clarify
      inconsistencies between studies. More work is also needed to identify differences
      between dopaminergic alterations in schizotypy compared to the dysfunctions
      observed in schizophrenia. 

PMID- 25566106
TI  - Low number of luminance levels in the luminance noise increases color
      discrimination thresholds estimated with pseudoisochromatic stimuli.
AB  - In pseudoisochromatic stimuli the presence of spatial and luminance noise forces
      the subject to discriminate the target from the background solely on the basis of
      chromaticity difference. Color-blind subjects may show difficulty to identify the
      target due to the elimination of borders and brightness clues caused by the
      luminance and spatial noise. Few studies have fully described the features of
      pseudoisochromatic stimuli. Fewer investigators have focused their studies in the
      effects of specific pseudoisochromatic parameters on color discrimination. We
      used the Cambridge Color Test (CCT) to investigate the influence on color
      discrimination thresholds due to the number of luminance levels present in the
      luminance noise. The CCT default has six luminance steps; however, in our
      investigation a total of eight different conditions were tested from 2 to 16
      luminance steps. It was found that the CCT provided very robust values for color
      discrimination thresholds, which were degraded only for very small number of
      luminance steps. When the number of steps was increased, the color discrimination
      thresholds improved from 2 to 6 luminance steps and gradually reached a plateau
      for 10 or more luminance steps. The area of color discrimination ellipses as a
      function of luminance steps matches the relative proportion of ineffective
      contrasts between mosaic patches as a function of luminance steps, assuming that
      contrast becomes ineffective for values 18.6% or less. The lower number of color
      and luminance interactions in these conditions could explain the measured
      increase of color discrimination thresholds. The primary conclusion from this
      investigation was that results from pseudoisochromatic tests should have their
      parameters described in more detail. This type of description would allow a
      better understanding of the results provided, interpretations, and therefore
      cross study comparison of results obtained from different laboratories. 

PMID- 25566107
TI  - Visiting Richard Serra's "Promenade" sculpture improves postural control and
      judgment of subjective visual vertical.
AB  - Body sway while maintaining an upright quiet stance reflects an active process of
      balance based on the integration of visual, vestibular, somatosensory, and
      proprioceptive inputs. Richard Serra's Promenade sculpture featured in the 2008
      Monumenta exhibition at the Grand Palais in Paris, France is herein hypothesized
      to have stimulated the body's vertical and longitudinal axes as it showcased five
      monumental rectangular solids pitched at a 1.69( degrees ) angle. Using
      computerized dynamic posturography we measured the body sway of 23 visitors when
      fixating a cross, or when observing the artwork (fixating it or actively
      exploring it with eye movements) before and after walking around and alongside
      the sculpture (i.e., before and after a promenade). A first fixation at the
      sculpture increased medio-lateral stability (in terms of spectral power of body
      sway). Eye movement exploration in the depth of the sculpture increased antero
      posterior stability [in terms of spectral power and canceling time (CT) of body
      sway] at the expense of medio-lateral stability (in terms of CT). Moreover, a
      medio-lateral instability associated with eye movement exploration before the
      promenade (in terms of body sway sensu stricto) was canceled after the promenade.
      Finally, the overall medio-lateral stability (in terms of spectral power)
      increased after the promenade. Fourteen additional visitors were asked to stand
      in a dark room and adjust a luminous line to what they considered to be the earth
      vertical axis. The promenade executed within the sculpted environment afforded by
      Serra's monumental statuary works resulted in significantly improved performances
      on the subjective visual vertical test. We attribute these effects to the
      sculpted environment provided by the exhibition which may have acted as a kind of
      physiologic "training ground" thereby improving the visitors' overall sense of
      visual perspective, equilibrium, and gravity. 

PMID- 25566108
TI  - Response selection difficulty modulates the behavioral impact of rapidly learnt
      action effects.
AB  - It is well-established that we can pick up action effect associations when acting
      in a free-choice intentional mode. However, it is less clear whether and when
      action effect associations are learnt and actually affect behavior if we are
      acting in a forced-choice mode, applying a specific stimulus-response (S-R) rule.
      In the present study, we investigated whether response selection difficulty
      imposed by S-R rules influences the initial rapid learning and the behavioral
      expression of previously learnt but weakly practiced action effect associations
      when those are re-activated by effect exposure. Experiment 1 showed that the
      rapid learning of action effect associations is not directly influenced by
      response selection difficulty. By contrast, the behavioral expression of re
      activated action effect associations is prevented when actions are directly
      activated by highly over-learnt response cues and thus response selection
      difficulty is low. However, all three experiments showed that if response
      selection difficulty is sufficiently high during re-activation, the same action
      effect associations do influence behavior. Experiments 2 and 3 revealed that the
      effect of response selection difficulty cannot be fully reduced to giving action
      effects more time to prime an action, but seems to reflect competition during
      response selection. Finally, the present data suggest that when multiple novel
      rules are rapidly learnt in succession, which requires a lot of flexibility,
      action effect associations continue to influence behavior only if response
      selection difficulty is sufficiently high. Thus, response selection difficulty
      might modulate the impact of experiencing multiple learning episodes on action
      effect expression and learning, possibly via inducing different strategies. 

PMID- 25566109
TI  - Engagement in community music classes sparks neuroplasticity and language
      development in children from disadvantaged backgrounds.
AB  - Children from disadvantaged backgrounds often face impoverished auditory
      environments, such as greater exposure to ambient noise and fewer opportunities
      to participate in complex language interactions during development. These
      circumstances increase their risk for academic failure and dropout. Given the
      academic and neural benefits associated with musicianship, music training may be
      one method for providing auditory enrichment to children from disadvantaged
      backgrounds. We followed a group of primary-school students from gang reduction
      zones in Los Angeles, CA, USA for 2 years as they participated in Harmony
      Project. By providing free community music instruction for disadvantaged
      children, Harmony Project promotes the healthy development of children as
      learners, the development of children as ambassadors of peace and understanding,
      and the development of stronger communities. Children who were more engaged in
      the music program-as defined by better attendance and classroom participation
      developed stronger brain encoding of speech after 2 years than their less-engaged
      peers in the program. Additionally, children who were more engaged in the program
      showed increases in reading scores, while those less engaged did not show
      improvements. The neural gains accompanying music engagement were seen in the
      very measures of neural speech processing that are weaker in children from
      disadvantaged backgrounds. Our results suggest that community music programs such
      as Harmony Project provide a form of auditory enrichment that counteracts some of
      the biological adversities of growing up in poverty, and can further support
      community-based interventions aimed at improving child health and wellness. 

PMID- 25566110
TI  - Synesthesia: an introduction.

PMID- 25566112
TI  - Toward an experimental account of argumentation: the case of the slippery slope
      and the ad hominem arguments.
AB  - Argumentation is a crucial component of our lives. Although in the absence of
      rational debate our legal, political, and scientific systems would not be
      possible, there is still no integrated area of research on the psychology of
      argumentation. Furthermore, classical theories of argumentation are normative
      (i.e., the acceptability of an argument is determined by a set of norms or
      logical rules), which sometimes creates a dissociation between the theories and
      people's behavior. We think the current challenge for psychology is to bring
      together the cognitive and normative accounts of argumentation. In this article,
      we exemplify this point by analyzing two cases of argumentative structures
      experimentally studied in the context of cognitive psychology. Specifically, we
      focus on the slippery slope argument and the ad hominem argument under the
      frameworks of Bayesian and pragma-dialectics approaches, respectively. We think
      employing more descriptive and experimental accounts of argumentation would help
      Psychology to bring closer the cognitive and normative accounts of argumentation
      with the final goal of establishing an integrated area of research on the
      psychology of argumentation. 

PMID- 25566111
TI  - The predictive mind and the experience of visual art work.
AB  - Among the main challenges of the predictive brain/mind concept is how to link
      prediction at the neural level to prediction at the cognitive-psychological level
      and finding conceptually robust and empirically verifiable ways to harness this
      theoretical framework toward explaining higher-order mental and cognitive
      phenomena, including the subjective experience of aesthetic and symbolic forms.
      Building on the tentative prediction error account of visual art, this article
      extends the application of the predictive coding framework to the visual arts. It
      does so by linking this theoretical discussion to a subjective, phenomenological
      account of how a work of art is experienced. In order to engage more deeply with
      a work of art, viewers must be able to tune or adapt their prediction mechanism
      to recognize art as a specific class of objects whose ontological nature defies
      predictability, and they must be able to sustain a productive flow of predictions
      from low-level sensory, recognitional to abstract semantic, conceptual, and
      affective inferences. The affective component of the process of predictive error
      optimization that occurs when a viewer enters into dialog with a painting is
      constituted both by activating the affective affordances within the image and by
      the affective consequences of prediction error minimization itself. The
      predictive coding framework also has implications for the problem of the
      culturality of vision. A person's mindset, which determines what top-down
      expectations and predictions are generated, is co-constituted by culture-relative
      skills and knowledge, which form hyperpriors that operate in the perception of
      art. 

PMID- 25566113
TI  - Language specific listening of Japanese geminate consonants: a cross-linguistic
      study.
AB  - Various aspects of linguistic experience influence the way we segment, represent,
      and process speech signals. The Japanese phonetic and orthographic systems
      represent geminate consonants (double consonants, e.g., /ss/, /kk/) in a unique
      way compared to other languages: one abstract representation is used to
      characterize the first part of geminate consonants despite the acoustic
      difference between two distinct realizations of geminate consonants (silence in
      the case of e.g., stop consonants and elongation in the case of fricative
      consonants). The current study tests whether this discrepancy between abstract
      representations and acoustic realizations influences how native speakers of
      Japanese perceive geminate consonants. The experiments used pseudo words
      containing either the geminate consonant /ss/ or a manipulated version in which
      the first part was replaced by silence /_s/. The sound /_s/ is acoustically
      similar to /ss/, yet does not occur in everyday speech. Japanese listeners
      demonstrated a bias to group these two types into the same category while Italian
      and Dutch listeners distinguished them. The results thus confirmed that
      distinguishing fricative geminate consonants with silence from those with
      sustained frication is not crucial for Japanese native listening. Based on this
      observation, we propose that native speakers of Japanese tend to segment
      geminated consonants into two parts and that the first portion of fricative
      geminates is perceptually similar to a silent duration. This representation is
      compatible with both Japanese orthography and phonology. Unlike previous studies
      that were inconclusive in how native speakers segment geminate consonants, our
      study demonstrated a relatively strong effect of Japanese specific listening.
      Thus the current experimental methods may open up new lines of investigation into
      the relationship between development of phonological representation, orthography
      and speech perception. 

PMID- 25566114
TI  - Perceived displacement explains wolfpack effect.
AB  - We investigate the influence of perceived displacement of moving agent-like
      stimuli on the performance in dynamic interactive tasks. In order to reliably
      measure perceived displacement we utilize multiple tasks with different task
      demands. The perceived center of an agent's body is displaced in the direction in
      which the agent is facing and this perceived displacement is larger than the
      theoretical position of the center of mass would predict. Furthermore, the
      displacement in the explicit judgment is dissociated from the displacement
      obtained by the implicit measures. By manipulating the location of the pivot
      point, we show that it is not necessary to postulate orientation as an additional
      cue utilized by perception, as has been suggested by earlier studies. These
      studies showed that the agent's orientation influences the detection of chasing
      motion and the detection-related performance in interactive tasks. This influence
      has been labeled wolfpack effect. In one of the demonstrations of the wolfpack
      effect participants control a green circle on a display with a computer mouse. It
      has been shown that participants avoid display areas with agents pointing toward
      the green circle. Participants do so in favor of areas where the agents point in
      the direction perpendicular to the circle. We show that this avoidance behavior
      arises because the agent's pivot point selected by the earlier studies is
      different from where people locate the center of agent's body. As a consequence,
      the nominal rotation confounds rotation and translation. We show that the
      avoidance behavior disappears once the pivot point is set to the center of
      agent's body. 

PMID- 25566115
TI  - Multiscale Enaction Model (MEM): the case of complexity and "context-sensitivity"
      in vision.
AB  - I review the data on human visual perception that reveal the critical role played
      by non-visual contextual factors influencing visual activity. The global
      perspective that progressively emerges reveals that vision is sensitive to
      multiple couplings with other systems whose nature and levels of abstraction in
      science are highly variable. Contrary to some views where vision is immersed in
      modular hard-wired modules, rather independent from higher-level or other non
      cognitive processes, converging data gathered in this article suggest that visual
      perception can be theorized in the larger context of biological, physical, and
      social systems with which it is coupled, and through which it is enacted.
      Therefore, any attempt to model complexity and multiscale couplings, or to
      develop a complex synthesis in the fields of mind, brain, and behavior, shall
      involve a systematic empirical study of both connectedness between systems or
      subsystems, and the embodied, multiscale and flexible teleology of subsystems.
      The conceptual model (Multiscale Enaction Model [MEM]) that is introduced in this
      paper finally relates empirical evidence gathered from psychology to
      biocomputational data concerning the human brain. Both psychological and
      biocomputational descriptions of MEM are proposed in order to help fill in the
      gap between scales of scientific analysis and to provide an account for both the
      autopoiesis-driven search for information, and emerging perception. 

PMID- 25566116
TI  - Does bilingual experience affect early visual perceptual development?
AB  - Visual attention and perception develop rapidly during the first few months after
      birth, and these behaviors are critical components in the development of language
      and cognitive abilities. Here we ask how early bilingual experiences might lead
      to differences in visual attention and perception. Experiments 1-3 investigated
      the looking behavior of monolingual and bilingual infants when presented with
      social (Experiment 1), mixed (Experiment 2), or non-social (Experiment 3)
      stimuli. In each of these experiments, infants' dwell times (DT) and number of
      fixations to areas of interest (AOIs) were analyzed, giving a sense of where the
      infants looked. To examine how the infants looked at the stimuli in a more global
      sense, Experiment 4 combined and analyzed the saccade data collected in
      Experiments 1-3. There were no significant differences between monolingual and
      bilingual infants' DTs, AOI fixations, or saccade characteristics (specifically,
      frequency, and amplitude) in any of the experiments. These results suggest that
      monolingual and bilingual infants process their visual environments similarly,
      supporting the idea that the substantial cognitive differences between
      monolinguals and bilinguals in early childhood are more related to active
      vocabulary production than perception of the environment. 

PMID- 25566117
TI  - Revisiting shyness and sociability: a preliminary investigation of hormone-brain
      behavior relations.
AB  - Shyness and sociability are two fundamental personality dimensions that are
      conceptually and empirically orthogonal and are conserved across cultures,
      development, and phylogeny. However, we know relatively little regarding how
      shyness and sociability are represented and maintained in the brain. Here we
      examined neural responses to the processing of different types of social threat
      using event-related fMRI, the salivary cortisol awakening response (CAR), and
      sociability in young adults selected for high and low shyness. Shy adults who
      exhibited a relatively higher CAR displayed neural activity in putative brain
      regions involved in emotional conflict and awareness, and were more sociable. In
      contrast, shy adults who displayed a relatively lower CAR exhibited neural
      activity in putative brain regions linked to fear and withdrawal, and were
      unsociable. Results revealed no systematic brain responses to social threat
      processing that correlated with the CAR in non-shy adults. These preliminary
      results suggest that individual differences in waking morning cortisol levels may
      influence neural processes that facilitate either social approach or withdrawal
      among people who are shy. Findings are discussed in relation to their theoretical
      and clinical implications for moving beyond longstanding descriptive to
      explanatory models of shyness and sociability and for understanding individual
      differences in social behavior in general. 

PMID- 25566118
TI  - Navigating beyond "here & now" affordances-on sensorimotor maturation and "false
      belief" performance.
AB  - How and when do we learn to understand other people's perspectives and possibly
      divergent beliefs? This question has elicited much theoretical and empirical
      research. A puzzling finding has been that toddlers perform well on so-called
      implicit false belief (FB) tasks but do not show such capacities on traditional
      explicit FB tasks. I propose a navigational approach, which offers a hitherto
      ignored way of making sense of the seemingly contradictory results. The proposal
      involves a distinction between how we navigate FBs as they relate to (1) our
      current affordances (here & now navigation) as opposed to (2) presently non
      actual relations, where we need to leave our concrete embodied/situated viewpoint
      (counterfactual navigation). It is proposed that whereas toddlers seem able to
      understand FBs in their current affordance space, they do not yet possess the
      resources to navigate in abstraction from such concrete affordances, which
      explicit FB tests seem to require. It is hypothesized that counterfactual
      navigation depends on the development of "sensorimotor priors," i.e., statistical
      expectations of own kinesthetic re-afference, which evidence now suggests matures
      around age four, consistent with core findings of explicit FB performance. 

PMID- 25566119
TI  - Changes across the psychometric function following perceptual learning of an RSVP
      reading task.
AB  - Several recent studies have shown that perceptual learning can result in
      improvements in reading speed for people with macular disease (e.g., Chung, 2011;
      Tarita-Nistor et al., 2014). The improvements were reported as an increase in
      reading speed defined by specific criteria; however, little is known about how
      other properties of the reading performance or the participants' perceptual
      responses change as a consequence of learning. In this paper, we performed
      detailed analyses of data following perceptual learning using an RSVP (rapid
      serial visual presentation) reading task, looking beyond the change in reading
      speed defined by the threshold at a given accuracy on a psychometric function
      relating response accuracy with word exposure duration. Specifically, we explored
      the statistical characteristics of the response data to address two specific
      questions: was there a change in the slope of the psychometric function and did
      the improvements in performance occur consistently across different word exposure
      durations? Our results show that there is a general steepening of the slope of
      the psychometric function, leading to non-uniform improvements across stimulus
      levels. 

PMID- 25566120
TI  - Minimizing bugs in cognitive neuroscience programming.

PMID- 25566121
TI  - Assessing children's empathy through a Spanish adaptation of the Basic Empathy
      Scale: parent's and child's report forms.
AB  - The aim of the current research was to study cognitive and affective empathy in
      children aged 6-12 years old, and their associations with children's family
      environment and social adjustment. For this purpose, we developed the Spanish
      version of the Basic Empathy Scale (BES), self- and parent-report forms.
      Factorial analyses confirmed a two-component model of empathy in both self- and
      parent-report forms. Concordance between parent-child measures of empathy was low
      for cognitive and affective factors. Analyses of variance on the cognitive and
      affective components brought a significant effect of age for self-reported
      cognitive empathy, with older children scoring higher than younger ones. Gender
      brought out a significant principal effect for self-reported affective empathy,
      with girls scoring higher than boys. No other main effects were found for age and
      gender for the rest of the factors analyzed. Children's empathy was associated
      with socioeconomic status and other family socialization processes, as well as
      children' social behaviors. Overall the new measures provided a coherent view of
      empathy in middle childhood and early adolescence when measured through self and
      parent reports, and illustrate the similarity of the validity of the BES in a
      European-Spanish culture. 

PMID- 25566123
TI  - A study on reintegration of street children in Burundi: experienced violence and
      maltreatment are associated with mental health impairments and impeded
      educational progress.
AB  - Street children are exposed to violence, and subsist in poor and generally
      precarious conditions. In conflict regions, institutional care facilities are
      often the only well established way to care for vulnerable children. Providing
      access to school education is considered to be key to allow successful
      integration into society. However, adverse effects of psychological disorders may
      pose another serious obstacle. In semi-structured interviews in a sample of 112
      Burundian male youths (mean age = 15.9 years), we assessed exposure to traumatic
      stressors, regularly and recently occurring violence as well as prevalence of
      posttraumatic stress disorder (PTSD), depression, substance dependence, suicidal
      risk, and progress in school. Former street children (n = 32) and other
      vulnerable children (n = 50) in a residential center were compared to children
      living in the streets (n = 15) or with families (n = 15). While the children
      living in the center were less regularly exposed to violence and reported less
      substance dependence than street children, PTSD symptoms were common among the
      former street children. Furthermore, we provided empirical evidence that for the
      children living in the center, recently experienced violence - mostly minor
      physical conflicts, psychological violence and neglect - was associated with
      increased PTSD symptomatology and impeded progress in school. In a population of
      children who experienced many traumatic incidences and a lot of violence, even
      minor violent events may trigger and reinforce PTSD symptoms. Hence controlling
      exposure to violence and addressing mental ill-health in vulnerable children is
      mandatory for reintegration. 

PMID- 25566124
TI  - Teachers' emotional experiences and exhaustion as predictors of emotional labor
      in the classroom: an experience sampling study.
AB  - Emotional exhaustion (EE) is the core component in the study of teacher burnout,
      with significant impact on teachers' professional lives. Yet, its relation to
      teachers' emotional experiences and emotional labor (EL) during instruction
      remains unclear. Thirty-nine German secondary teachers were surveyed about their
      EE (trait), and via the experience sampling method on their momentary (state; N =
      794) emotional experiences (enjoyment, anxiety, anger) and momentary EL
      (suppression, faking). Teachers reported that in 99 and 39% of all lessons, they
      experienced enjoyment and anger, respectively, whereas they experienced anxiety
      less frequently. Teachers reported suppressing or faking their emotions during
      roughly a third of all lessons. Furthermore, EE was reflected in teachers'
      decreased experiences of enjoyment and increased experiences of anger. On an
      intra-individual level, all three emotions predict EL, whereas on an inter
      individual level, only anger evokes EL. Explained variances in EL (within: 39%,
      between: 67%) stress the relevance of emotions in teaching and within the context
      of teacher burnout. Beyond implying the importance of reducing anger, our
      findings suggest the potential of enjoyment lessening EL and thereby reducing
      teacher burnout. 

PMID- 25566122
TI  - Music training and empathy positively impact adults' sensitivity to infant
      distress.
AB  - Crying is the most powerful auditory signal of infant need. Adults' ability to
      perceive and respond to crying is important for infant survival and in the
      provision of care. This study investigated a number of listener variables that
      might impact on adults' perception of infant cry distress, namely parental
      status, musical training, and empathy. Sensitivity to infant distress was tested
      using a previously validated task, which experimentally manipulated distress by
      varying the pitch of infant cries. This task required that participants
      discriminate between pitch differences and interpret these as differences in
      infant distress. Parents with musical training showed a significant advantage on
      this task when compared with parents without. The extent of the advantage was
      correlated with the amount of self-reported musical training. For non-parents,
      individual differences in empathy were associated with task performance, with
      higher empathy scores corresponding to greater sensitivity to infant distress. We
      suggest that sensitivity to infant distress can be impacted by a number of
      listener variables, and may be amenable to training. 

PMID- 25566125
TI  - When too much of a novel thing may be what's "bad": commentary on Fisher, Godwin,
      and Seltman (2014).

PMID- 25566126
TI  - Internally generated conscious contents: interactions between sustained mental
      imagery and involuntary subvocalizations.
AB  - The conscious field includes not only representations about external stimuli
      (e.g., percepts), but also conscious contents associated with internal states,
      such as action-related intentions (e.g., urges). Although understudied, the
      latter may provide unique insights into the nature of consciousness. To
      illuminate these phenomena, in a new experimental paradigm [Reflexive Imagery
      Task (RIT)], participants were instructed to not subvocalize the names of
      visually-presented objects. Each object was presented for 10 s on a screen.
      Participants indicated whenever they involuntarily subvocalized the object name.
      Research has revealed that it is difficult to suppress such subvocalizations,
      which occur on over 80% of the trials. Can the effect survive if one
      intentionally generates a competing (internally-generated) conscious content? If
      so, this would suggest that intentional and unintentional contents can co-exist
      simultaneously in consciousness in interesting ways. To investigate this
      possibility, in one condition, participants were instructed to reiteratively
      subvocalize a speech sound ("da, da, da") throughout the trial. This internally
      generated content is self-generated and intentional. Involuntary subvocalizations
      of object names still arose on over 80% of the trials. One could hypothesize that
      subvocalizations occurred because of the pauses between the intended speech
      sounds, but this is inconsistent with the observation that comparable results
      arose even when participants subvocalized a continuous, unbroken hum ("daaa....")
      throughout the trial. Regarding inter-content interactions, the continuous hum
      and object name seem to co-exist simultaneously in consciousness. This intriguing
      datum requires further investigation. We discuss the implications of this new
      paradigm for the study of internally-generated conscious contents. 

PMID- 25566127
TI  - Patterns of differences in wayfinding performance and correlations among
      abilities between persons with and without Down syndrome and typically developing
      children.
AB  - Down syndrome (DS) impacts several brain regions including the hippocampus and
      surrounding structures that have responsibility for important aspects of
      navigation and wayfinding. Hence it is reasonable to expect that DS may result in
      a reduced ability to engage in these skills. Two experiments are reported that
      evaluated route-learning of youth with DS, youth with intellectual disability
      (ID) and not DS, and typically developing (TD) children matched on mental age
      (MA). In both experiments, participants learned routes with eight choice point
      presented via computer. Several objects were placed along the route that could be
      used as landmarks. Participants navigated the route once with turn indicators
      pointing the way and then retraced the route without them. In Experiment 1 we
      found that the TD children and ID participants performed very similarly. They
      learned the route in the same number of attempts, committed the same number of
      errors while learning the route, and recalled approximately the same number of
      landmarks. The participants with DS performed significantly worse on both
      measures of navigation (attempts and errors) and also recalled significantly
      fewer landmarks. In Experiment 2, we attempted to reduce TD and ID vs DS
      differences by focusing participants' attention on the landmarks. Half of the
      participants in each group were instructed to identify the landmarks as they
      passed them the first time. The participants with DS again committed more errors
      than the participants in the ID and TD groups in the navigation task. In
      addition, they recalled fewer landmarks. While landmark identification improved
      landmark memory for both groups, it did not have a significant impact on
      navigation. Participants with DS still performed more poorly than did the TD and
      ID participants. Of additional interest, we observed that the performance of
      persons with DS correlated with different ability measures than did the
      performance of the other groups. The results the two experiments point to a
      problem in navigation for persons with DS that exceeds expectations based solely
      on intellectual level. 

PMID- 25566128
TI  - Long term impact of emotional, social and cognitive intelligence competencies and
      GMAT on career and life satisfaction and career success.
AB  - Career scholars have called for a broader definition of career success by
      inviting greater exploration of its antecedents. While success in various jobs
      has been predicted by intelligence and in other studies by competencies,
      especially in management, long term impact of having intelligence and using
      competencies has not been examined. Even in collegiate outcome studies, few have
      examined the longer term impact on graduates' careers or lives. This study
      assesses the impact of demonstrated emotional, social, and cognitive intelligence
      competencies assessed at graduation and g measured through GMAT at entry from an
      MBA program on career and life satisfaction, and career success assessed 5 to 19
      years after graduation. Using behavioral measures of competencies (i.e., as
      assessed by others), we found that emotional intelligence competencies predict
      career satisfaction and success. Adaptability had a positive impact, but
      influence had the opposite effect on these career measures and life satisfaction.
      Life satisfaction was negatively affected by achievement orientation and
      positively affected by teamwork. Current salary, length of marriage, and being
      younger at time of graduation positively affect all three measures of life and
      career satisfaction and career success. GMAT (as a measure of g) predicted life
      satisfaction and career success to a slight but significant degree in the final
      model analyzed. Meanwhile, being female and number of children positively
      affected life satisfaction but cognitive intelligence competencies negatively
      affected it, and in particular demonstrated systems thinking was negative. 

PMID- 25566129
TI  - READING and FEELING: the effects of a literature-based intervention designed to
      increase emotional competence in second and third graders.
AB  - Emotional competence has an important influence on development in school. We
      hypothesized that reading and discussing children's books with emotional content
      increases children's emotional competence. To examine this assumption, we
      developed a literature-based intervention, named READING and FEELING, and tested
      it on 104 second and third graders in their after-school care center. Children
      who attended the same care center but did not participate in the emotion-centered
      literary program formed the control group (n = 104). Our goal was to promote
      emotional competence and to evaluate the effectiveness of the READING and FEELING
      program. Emotional competence variables were measured prior to the intervention
      and 9 weeks later, at the end of the program. Results revealed significant
      improvements in the emotional vocabulary, explicit emotional knowledge, and
      recognition of masked feelings. Regarding the treatment effect for detecting
      masked feelings, we found that boys benefited significantly more than girls.
      These findings underscore the assumption that children's literature is an
      appropriate vehicle to support the development of emotional competence in middle
      childhood. 

PMID- 25566130
TI  - Raspberry, not a car: context predictability and a phonological advantage in
      early and late learners' processing of speech in noise.
AB  - Second language learners perform worse than native speakers under adverse
      listening conditions, such as speech in noise (SPIN). No data are available on
      heritage language speakers' (early naturalistic interrupted learners') ability to
      perceive SPIN. The current study fills this gap and investigates the perception
      of Russian speech in multi-talker babble noise by the matched groups of high- and
      low-proficiency heritage speakers (HSs) and late second language learners of
      Russian who were native speakers of English. The study includes a control group
      of Russian native speakers. It manipulates the noise level (high and low), and
      context cloze probability (high and low). The results of the SPIN task are
      compared to the tasks testing the control of phonology, AXB discrimination and
      picture-word discrimination, and lexical knowledge, a word translation task, in
      the same participants. The increased phonological sensitivity of HSs interacted
      with their ability to rely on top-down processing in sentence integration, use
      contextual cues, and build expectancies in the high-noise/high-context condition
      in a bootstrapping fashion. HSs outperformed oral proficiency-matched late second
      language learners on SPIN task and two tests of phonological sensitivity. The
      outcomes of the SPIN experiment support both the early naturalistic advantage and
      the role of proficiency in HSs. HSs' ability to take advantage of the high
      predictability context in the high-noise condition was mitigated by their level
      of proficiency. Only high-proficiency HSs, but not any other non-native group,
      took advantage of the high-predictability context that became available with
      better phonological processing skills in high-noise. The study thus confirms high
      proficiency (but not low-proficiency) HSs' nativelike ability to combine bottom
      up and top-down cues in processing SPIN. 

PMID- 25566132
TI  - Tryptophan promotes charitable donating.
AB  - The link between serotonin (5-HT) and one of the most important elements of
      prosocial behavior, charity, has remained largely uninvestigated. In the present
      study, we tested whether charitable donating can be promoted by administering the
      food supplement L-Tryptophan (TRP), the biochemical precursor of 5-HT.
      Participants were compared with respect to the amount of money they donated when
      given the opportunity to make a charitable donation. As expected, compared to a
      neutral placebo, TRP appears to increase the participants' willingness to donate
      money to a charity. This result supports the idea that the food we eat may act as
      a cognitive enhancer modulating the way we think and perceive the world and
      others. 

PMID- 25566131
TI  - Processing speed enhances model-based over model-free reinforcement learning in
      the presence of high working memory functioning.
AB  - Theories of decision-making and its neural substrates have long assumed the
      existence of two distinct and competing valuation systems, variously described as
      goal-directed vs. habitual, or, more recently and based on statistical arguments,
      as model-free vs. model-based reinforcement-learning. Though both have been shown
      to control choices, the cognitive abilities associated with these systems are
      under ongoing investigation. Here we examine the link to cognitive abilities, and
      find that individual differences in processing speed covary with a shift from
      model-free to model-based choice control in the presence of above-average working
      memory function. This suggests shared cognitive and neural processes; provides a
      bridge between literatures on intelligence and valuation; and may guide the
      development of process models of different valuation components. Furthermore, it
      provides a rationale for individual differences in the tendency to deploy
      valuation systems, which may be important for understanding the manifold
      neuropsychiatric diseases associated with malfunctions of valuation. 

PMID- 25566133
TI  - Significant variations in Weber fraction for changes in inter-onset interval of a
      click train over the range of intervals between 5 and 300 ms.
AB  - It is a common psychophysical experience that a train of clicks faster than ca.
      30/s is heard as one steady sound, whereas temporal patterns occurring on a
      slower time scale are perceptually resolved as individual auditory events. This
      phenomenon suggests the existence of two different neural mechanisms for
      processing of auditory sequences with fast and slow repetition rates. To test
      this hypothesis we used Weber's law, which is known to be valid for perception of
      time intervals. Discrimination thresholds and Weber fractions (WFs) for 12 base
      inter-click intervals (ICIs) between 5 and 300 ms were measured from 10 normal
      hearing subjects by using an "up-down staircase" algorithm. The mean WF, which is
      supposed to be constant for any perceptual mechanism according to Weber's law,
      displayed significant variation with click rate. WFs decreased sharply from an
      average value of around 5% at repetition rates below 20 Hz to about 0.5% at rates
      above 67 Hz. Parallel to this steep transition, subjects reported that at rates
      below 20 Hz they perceived periodicity as a fast tapping rhythm, whereas at rates
      above 50 Hz the perceived quality was a pitch. Such a dramatic change in WF
      indicated the existence of two separate mechanisms for processing the click rate
      for long and short ICIs, based on temporal and spectral features, respectively. A
      range of rates between 20 and 33 Hz, in which the rate discrimination threshold
      was maximum, appears to be a region where both of the presumed time and pitch
      mechanisms are relatively insensitive to rate alterations. Based on this finding,
      we speculate that the interval-based perception mechanism ceases to function at
      around 20 Hz and the spectrum-based mechanism takes over at around 33 Hz; leaving
      a transitional gap in between, where neither of the two mechanisms is as
      sensitive. Another notable finding was a significant drop in WF for ICI = 100 ms,
      suggesting a connection of time perception to the electroencephalography alpha
      rhythm. 

PMID- 25566135
TI  - Confidence measurement in the light of signal detection theory.
AB  - We compare three alternative methods for eliciting retrospective confidence in
      the context of a simple perceptual task: the Simple Confidence Rating (a direct
      report on a numerical scale), the Quadratic Scoring Rule (a post-wagering
      procedure), and the Matching Probability (MP; a generalization of the no-loss
      gambling method). We systematically compare the results obtained with these three
      rules to the theoretical confidence levels that can be inferred from performance
      in the perceptual task using Signal Detection Theory (SDT). We find that the MP
      provides better results in that respect. We conclude that MP is particularly well
      suited for studies of confidence that use SDT as a theoretical framework. 

PMID- 25566134
TI  - Frequency of provision of knowledge of performance on skill acquisition in older
      persons.
AB  - The provision of feedback is a crucial factor for the evolution of the learner's
      performance. It is known that the knowledge of performance has the function of
      guiding the learner's attention to critical aspects of the movement pattern. The
      objective of this study was to examine the effect of frequency of knowledge of
      performance (KP) during the acquisition of the basketball free throw in older
      persons. Sixty active individuals (men and women) aged 60-69 years of age,
      divided into three experimental groups received KP in 100, 66, and 33% of their
      attempts during three practice sessions totaling 90 trials. The task was the
      basketball free throw. Volunteers were asked to conduct tests of immediate
      retention, 24 h retention, and 24 h transfer test, after the last practice
      session. During the acquisition phase, the volunteers received KP on the movement
      pattern on the previous attempt, which was obtained from a qualitative
      hierarchical checklist of the free throw (14 items). Sessions were recorded in
      order to confirm whether volunteers were able to score throughout sessions. ANOVA
      indicated that all individuals showed an improved performance in the retention
      and transfer tests. But the KP frequency of 66% was superior in both qualitative
      (movement pattern) and quantitative (score) measurements throughout the trials (p
      <= 0.05). In conclusion older persons seem to need an optimal KP frequency supply
      during the learning process. 

PMID- 25566136
TI  - The ideological divide and climate change opinion: "top-down" and "bottom-up"
      approaches.
AB  - The United States wields disproportionate global influence in terms of carbon
      dioxide emissions and international climate policy. This makes it an especially
      important context in which to examine the interplay among social, psychological,
      and political factors in shaping attitudes and behaviors related to climate
      change. In this article, we review the emerging literature addressing the liberal
      conservative divide in the U.S. with respect to thought, communication, and
      action concerning climate change. Because of its theoretical and practical
      significance, we focus on the motivational basis for skepticism and inaction on
      the part of some, including "top-down" institutional forces, such as corporate
      strategy, and "bottom-up" psychological factors, such as ego, group, and system
      justification. Although more research is needed to elucidate fully the social,
      cognitive, and motivational bases of environmental attitudes and behavior, a
      great deal has been learned in just a few years by focusing on specific
      ideological factors in addition to general psychological principles. 

PMID- 25566137
TI  - Walking boosts your performance in making additions and subtractions.
AB  - Previous research demonstrates that the processing of spatial information and
      numerical magnitude are strictly interwoven. Recent studies also provide
      converging evidence that number processing is influenced by body movements. In
      the present study we further investigate this issue by focusing on whether and
      how motions experienced with the whole body can influence arithmetical
      calculations. We asked participants to make additions or subtractions while
      experiencing leftward and rightward motions. Data revealed the emergence of a
      congruency effect between the orientation inferred by the type of arithmetical
      calculations and the type of motions experienced along an horizontal axis. 

PMID- 25566138
TI  - Facial emotion processing and recognition among maltreated children: a systematic
      literature review.
AB  - Exposure to maltreatment is associated with biological, psychological, and social
      development impairments in children. This systematic literature review sought to
      determine whether an association exists between child maltreatment and facial
      emotion processing and recognition. The search was conducted using the databases
      PubMed, PsycINFO, and SciELO using the following keywords: "maltreatment,"
      "adversity," "neglect," "sexual abuse," "emotional abuse," "physical abuse,"
      "child(*)," "early," "infant," "face," "facial," "recognition," "expression,"
      "emotion(*)," and "impairment." Seventeen articles were selected and analyzed.
      Maltreated children tended to exhibit less accuracy in global facial tasks and
      showed greater reactivity, response bias, and electrophysiological activation of
      specific brain areas in response to faces expressing negative emotions,
      especially anger. We concluded that the results of this review are exploratory
      and non-conclusive due to the small number of studies published and the wide
      variety of aims and procedures. Those shortcomings notwithstanding, the results
      indicate definite tendencies and gaps that should be more thoroughly explored in
      future studies. 

PMID- 25566139
TI  - Blinded by magic: eye-movements reveal the misdirection of attention.
AB  - Recent studies (e.g., Kuhn and Tatler, 2005) have suggested that magic tricks can
      provide a powerful and compelling domain for the study of attention and
      perception. In particular, many stage illusions involve attentional misdirection,
      guiding the observer's gaze to a salient object or event, while another critical
      action, such as sleight of hand, is taking place. Even if the critical action
      takes place in full view, people typically fail to see it due to inattentional
      blindness (IB). In an eye-tracking experiment, participants watched videos of a
      new magic trick, wherein a coin placed beneath a napkin disappears, reappearing
      under a different napkin. Appropriately deployed attention would allow
      participants to detect the "secret" event that underlies the illusion (a moving
      coin), as it happens in full view and is visible for approximately 550 ms.
      Nevertheless, we observed high rates of IB. Unlike prior research, eye-movements
      during the critical event showed different patterns for participants, depending
      upon whether they saw the moving coin. The results also showed that when
      participants watched several "practice" videos without any moving coin, they
      became far more likely to detect the coin in the critical trial. Taken together,
      the findings are consistent with perceptual load theory (Lavie and Tsal, 1994). 

PMID- 25566140
TI  - Interacting hands: the role of attention for the joint Simon effect.
AB  - Recent research in monkeys and humans has shown that the presence of the hands
      near an object enhances spatial processing for objects presented near the hand.
      This study aimed to test the effect of hand position on the joint Simon effect.
      In Experiment 1, two human co-actors shared a Simon task while placing their
      response hands either near the objects appearing on the monitor or away from the
      monitor. Experiment 2 varied each co-actor's hand position independently.
      Experiment 3 tested whether enhanced spatial processing for objects presented
      near the hand is obtained when replacing one of the two co-actors by a non-human
      event-producing rubber hand. Experiment 1 provided evidence for a Simon effect.
      Hand position significantly modulated the size of the Simon effect in the joint
      Simon task showing an increased Simon effect when the hands of both actors were
      located near the objects on the monitor, than when they were located away from
      the monitor. Experiment 2 replicated this finding showing an increased Simon
      effect when the actor's hand was located near the objects on the monitor, but
      only when the co-actor also produced action events in spatial reference. A
      similar hand position effect was observed in Experiment 3 when a non-human rubber
      hand replaced the human co-actor. These findings suggest that external action
      events that are produced in spatial reference bias the distribution of attention
      to the area near the hand. This strengthens the weight of the spatial response
      codes (referential coding) and hence increases the joint Simon effect. 

PMID- 25566141
TI  - Attention mechanisms and the mosaic evolution of speech.
AB  - There is still no categorical answer as to why humans, and no other species, have
      speech, or why speech is the way it is. Several purely anatomical arguments have
      been put forward, but they have been shown to be false, biologically implausible,
      or of limited scope. This perspective paper supports the idea that evolutionary
      theories of speech could benefit from a focus on the cognitive mechanisms that
      make speech possible, for which antecedents in evolutionary history and brain
      correlates can be found. This type of approach is part of a very recent but
      rapidly growing trend that has already provided crucial insights on the nature of
      human speech by focusing on the biological bases of vocal learning. Here we
      contend that a general mechanism of attention, which manifests itself not only in
      the visual but also in the auditory modality, might be one of the key ingredients
      of human speech, in addition to the mechanisms underlying vocal learning, and the
      pairing of facial gestures with vocalic units. 

PMID- 25566142
TI  - Understanding multilingualism and its implications.

PMID- 25566143
TI  - Individual differences in working memory capacity and workload capacity.
AB  - We investigated the relationship between working memory capacity (WMC) and
      workload capacity (WLC). Each participant performed an operation span (OSPAN)
      task to measure his/her WMC and three redundant-target detection tasks to measure
      his/her WLC. WLC was computed non-parametrically (Experiments 1 and 2) and
      parametrically (Experiment 2). Both levels of analyses showed that participants
      high in WMC had larger WLC than those low in WMC only when redundant information
      came from visual and auditory modalities, suggesting that high-WMC participants
      had superior processing capacity in dealing with redundant visual and auditory
      information. This difference was eliminated when multiple processes required
      processing for only a single working memory subsystem in a color-shape detection
      task and a double-dot detection task. These results highlighted the role of
      executive control in integrating and binding information from the two working
      memory subsystems for perceptual decision making. 

PMID- 25566144
TI  - Pitch enhancement facilitates word learning across visual contexts.
AB  - This study investigates word-learning using a new experimental paradigm that
      integrates three processes: (a) extracting a word out of a continuous sound
      sequence, (b) inferring its referential meanings in context, (c) mapping the
      segmented word onto its broader intended referent, such as other objects of the
      same semantic category, and to novel utterances. Previous work has examined the
      role of statistical learning and/or of prosody in each of these processes
      separately. Here, we combine these strands of investigation into a single
      experimental approach, in which participants viewed a photograph belonging to one
      of three semantic categories while hearing a complex, five-word utterance
      containing a target word. Six between-subjects conditions were tested with 20
      adult participants each. In condition 1, the only cue to word-meaning mapping was
      the co-occurrence of word and referents. This statistical cue was present in all
      conditions. In condition 2, the target word was sounded at a higher pitch. In
      condition 3, random words were sounded at a higher pitch, creating an
      inconsistent cue. In condition 4, the duration of the target word was lengthened.
      In conditions 5 and 6, an extraneous acoustic cue and a visual cue were
      associated with the target word, respectively. Performance in this word-learning
      task was significantly higher than that observed with simple co-occurrence only
      when pitch prominence consistently marked the target word. We discuss
      implications for the pragmatic value of pitch marking as well as the relevance of
      our findings to language acquisition and language evolution. 

PMID- 25566145
TI  - Approximate measurement invariance in cross-classified rater-mediated
      assessments.
AB  - An important assumption underlying meaningful comparisons of scores in rater
      mediated assessments is that measurement is commensurate across raters. When
      raters differentially apply the standards established by an instrument, scores
      from different raters are on fundamentally different scales and no longer
      preserve a common meaning and basis for comparison. In this study, we developed a
      method to accommodate measurement noninvariance across raters when measurements
      are cross-classified within two distinct hierarchical units. We conceptualized
      random item effects cross-classified graded response models and used random
      discrimination and threshold effects to test, calibrate, and account for
      measurement noninvariance among raters. By leveraging empirical estimates of
      rater-specific deviations in the discrimination and threshold parameters, the
      proposed method allows us to identify noninvariant items and empirically estimate
      and directly adjust for this noninvariance within a cross-classified framework.
      Within the context of teaching evaluations, the results of a case study suggested
      substantial noninvariance across raters and that establishing an approximately
      invariant scale through random item effects improves model fit and predictive
      validity. 

PMID- 25566147
TI  - Building a bridge-an archeologist's perspective on the evolution of causal
      cognition.
AB  - The cognitive capacities of fossil humans cannot be studied directly. Taking the
      evolution of causal cognition as an example this article demonstrates the use of
      bridging arguments from archeological finds as starting point via
      identification/classification, behavioral reconstructions, and cognitive
      interpretations to psychological models. Generally, tool use is linked to some
      causal understanding/agent construal as the tool broadens the subject's specific
      capabilities by adding new characters to its action sphere. In human evolution,
      the distance between the primarily perceived problem and the solution satisfying
      this need increased markedly: from simple causal relations to effective chaining
      in secondary/modular tool use, and further to the use of composite tools,
      complementary tool sets and notional tools. This article describes the evolution
      of human tool behavior from the perspective of problem-solution-distance and
      discusses the implications for a linked development of causal cognition. 

PMID- 25566146
TI  - Another step closer to measuring the ghosts in the nursery: preliminary
      validation of the Trauma Reflective Functioning Scale.
AB  - The aim of this study was to examine preliminary evidence of the validity of the
      Trauma Reflective Functioning Scale and to investigate reflective functioning
      (RF) and attachment in pregnant women with histories of trauma, with a particular
      focus on the capacity to mentalize regarding trauma and its implications for
      adaptation to pregnancy and couple functioning. The Adult Attachment Interview
      was used to assess attachment, unresolved trauma and mentalization (measured as
      RF) regarding relationships with attachment figures (RF-G) and trauma (RF-T) in
      100 pregnant women with histories of abuse and neglect. The majority (63%) of
      women had insecure attachment states of mind and approximately half were
      unresolved regarding trauma. Furthermore, the majority of women manifested
      deficits specific to RF-T. Their RF-T was significantly lower than their RF-G;
      the findings indicate that women with histories of childhood abuse and neglect do
      not manifest a generic inhibition of reflectiveness, but a collapse of
      mentalization specific to trauma. Low RF-T, indicative of difficulty in
      considering traumatic experiences in mental state terms, was associated with
      difficulty in investment in the pregnancy and lack of positive feelings about the
      baby and motherhood. In addition, low RF-T was also associated with difficulties
      in intimate relationships. Results of a regression analysis with RF indicated
      that RF-T was the best predictor of investment in pregnancy and couple
      functioning. In sum, the study provides preliminary evidence that RF-T can be
      reliably measured and is a valid construct that has potential usefulness for
      research and clinical practice. It highlights the importance of mentalization
      specifically about trauma and suggests that it is not the experience of trauma
      per se, but the absence of mentalization regarding trauma that is associated with
      difficulties in close relationships and in making the transition to parenthood. 

PMID- 25566149
TI  - A task is a task is a task: putting complex span, n-back, and other working
      memory indicators in psychometric context.
AB  - Based on a meta-analysis, Redick and Lindsey (2013) found that complex span and n
      back tasks show an average correlation of r = 0.20, and concluded that "complex
      span and n-back tasks cannot be used interchangeably as working memory measures
      in research applications" (p. 1102). Here, we comment on this conclusion from a
      psychometric perspective. In addition to construct variance, performance on a
      test contains measurement error, task-specific variance, and paradigm-specific
      variance. Hence, low correlations among dissimilar indicators do not provide
      strong evidence for the existence, or absence, of a construct common to both
      indicators. One way to arrive at such evidence is to fit hierarchical latent
      factors that model task-specific, paradigm-specific, and construct variance. We
      report analyses for 101 younger and 103 older adults who worked on nine different
      working memory tasks. The data are consistent with a hierarchical model of
      working memory, according to which both complex span and n-back tasks are valid
      indicators of working memory. The working memory factor predicts 71% of the
      variance in a factor of reasoning among younger adults (83% for among older
      adults). When the working memory factor was restricted to any possible triplet of
      working memory tasks, the correlation between working memory and reasoning was
      inversely related to the average magnitude of the correlations among the
      indicators, indicating that more highly intercorrelated indicators may provide
      poorer coverage of the construct space. We stress the need to go beyond specific
      tasks and paradigms when studying higher-order cognitive constructs, such as
      working memory. 

PMID- 25566148
TI  - Cognitive and physiological effects of an acute physical activity intervention in
      elementary school children.
AB  - The aim of the present study was to investigate the effects of an acute physical
      activity intervention that included cognitive engagement on executive functions
      and on cortisol level in young elementary school children. Half of the 104
      participating children (6-8 years old) attended a 20-min sport sequence, which
      included cognitively engaging and playful forms of physical activity. The other
      half was assigned to a resting control condition. Individual differences in
      children's updating, inhibition, and shifting performance as well as salivary
      cortisol were assessed before (pre-test), immediately after (post-test), and 40
      min after (follow-up) the intervention or control condition, respectively.
      Results revealed a significantly stronger improvement in inhibition in the
      experimental group compared to the control group, while it appeared that acute
      physical activity had no specific effect on updating and shifting. The
      intervention effect on inhibition leveled out 40 min after physical activity.
      Salivary cortisol increased significantly more in the experimental compared to
      the control group between post-test and follow-up and results support partly the
      assumed inverted U-shaped relationship between cortisol level and cognitive
      performance. In conclusion, results indicate that acute physical activity that
      includes cognitive engagement may have immediate positive effects on inhibition,
      but not necessarily on updating and shifting in elementary school children. This
      positive effect may partly be explained through cortisol elevation after acute
      physical activity. 

PMID- 25566150
TI  - Adolescent and adult risk-taking in virtual social contexts.
AB  - There is a paucity of experimental data addressing how peers influence adolescent
      risk-taking. Here, we examined peer effects on risky decision-making in adults
      and adolescents using a virtual social context that enabled experimental control
      over the peer "interactions." 40 adolescents (age 11-18) and 28 adults (age 20
      38) completed a risk-taking (Wheel of Fortune) task under four conditions: in
      private; while being observed by (fictitious) peers; and after receiving 'risky'
      or 'safe' advice from the peers. For high-risk gambles (but not medium-risk or
      even gambles), adolescents made more risky decisions under peer observation than
      adults. Adolescents, but not adults, tended to resist 'safe' advice for high-risk
      gambles. Although both groups tended to follow 'risky' advice for high-risk
      gambles, adults did so more than adolescents. These findings highlight the
      importance of distinguishing between the effects of peer observation and peer
      advice on risky decision-making. 

PMID- 25566151
TI  - Sex differences in event-related potentials and attentional biases to emotional
      facial stimuli.
AB  - Attentional processes play an important role in the processing of emotional
      information. Previous research reported attentional biases during stimulus
      processing in anxiety and depression. However, sex differences in the processing
      of emotional stimuli and higher prevalence rates of anxiety disorders among
      women, compared to men, suggest that attentional biases may also differ between
      the two sexes. The present study used a modified version of the dot probe task
      with happy, angry, and neutral facial stimuli to investigate the time course of
      attentional biases in healthy volunteers. Moreover, associations of attentional
      biases with alexithymia were examined on the behavioral and physiological level.
      Event-related potentials were measured while 21 participants (11 women) performed
      the task, utilizing also for the first time a difference wave approach in the
      analysis to highlight emotion-specific aspects. Women showed overall enhanced
      probe P1 amplitudes compared to men, in particular after rewarding facial
      stimuli. Using the difference wave approach, probe P1 amplitudes appeared
      specifically enhanced with regard to congruently presented happy facial stimuli
      among women, compared to men. Both methods yielded enhanced probe P1 amplitudes
      after presentation of the emotional stimulus in the left compared to the right
      visual hemifield. Probe P1 amplitudes correlated negatively with self-reported
      alexithymia, most of these correlations were only observable in women. Our
      results suggest that women orient their attention to a greater extent to facial
      stimuli than men and corroborate that alexithymia is a correlate of reduced
      emotional reactivity on a neuronal level. We recommend using a difference wave
      approach when addressing attentional processes of orientation and disengagement
      also in future studies. 

PMID- 25566152
TI  - Number processing and arithmetic skills in children with cochlear implants.
AB  - Though previous findings report that hearing impaired children exhibit impaired
      language and arithmetic skills, our current understanding of how hearing and the
      associated language impairments may influence the development of arithmetic
      skills is still limited. In the current study numerical/arithmetic performance of
      45 children with a cochlea implant were compared to that of controls matched for
      hearing age, intelligence and sex. Our main results were twofold disclosing that
      children with CI show general as well as specific numerical/arithmetic
      impairments. On the one hand, we found an increased percentage of children with
      CI with an indication of dyscalculia symptoms, a general slowing in
      multiplication and subtraction as well as less accurate number line estimations.
      On the other hand, however, children with CI exhibited very circumscribed
      difficulties associated with place-value processing. Performance declined
      specifically when subtraction required a borrow procedure and number line
      estimation required the integration of units, tens, and hundreds instead of only
      units and tens. Thus, it seems that despite initially atypical language
      development, children with CI are able to acquire arithmetic skills in a
      qualitatively similar fashion as their normal hearing peers. Nonetheless, when
      demands on place-value understanding, which has only recently been proposed to be
      language mediated, hearing impaired children experience specific difficulties. 

PMID- 25566153
TI  - Manual (a)symmetries in grasp posture planning: a short review.
AB  - Many activities of daily living require that we physically interact with one or
      more objects. Object manipulation provides an intriguing domain in which the
      presence and extent of manual asymmetries can be studied on a motor planning and
      a motor execution level. In this literature review we present a state of the art
      for manual asymmetries at the level of motor planning during object manipulation.
      First, we introduce pioneering work on grasp posture planning. We then sketch the
      studies investigating the impact of future task demands during unimanual and
      bimanual object manipulation tasks in healthy adult populations. In sum, in
      contrast to motor execution, there is little evidence for hand-based performance
      differences in grasp posture planning. We discuss potential reasons for the lack
      of manual asymmetries in motor planning and outline potential avenues of future
      research. 

PMID- 25566154
TI  - Timing skills and expertise: discrete and continuous timed movements among
      musicians and athletes.
AB  - INTRODUCTION: Movement-based expertise relies on precise timing of movements and
      the capacity to predict the timing of events. Music performance involves discrete
      rhythmic actions that adhere to regular cycles of timed events, whereas many
      sports involve continuous movements that are not timed in a cyclical manner. It
      has been proposed that the precision of discrete movements relies on event timing
      (clock mechanism), whereas continuous movements are controlled by emergent
      timing. We examined whether movement-based expertise influences the timing mode
      adopted to maintain precise rhythmic actions. MATERIALS AND METHOD: Timing
      precision was evaluated in musicians, athletes and control participants. Discrete
      and continuous movements were assessed using finger-tapping and circle-drawing
      tasks, respectively, based on the synchronization-continuation paradigm. In
      Experiment 1, no auditory feedback was provided in the continuation phase of the
      trials, whereas in Experiment 2 every action triggered a feedback tone. RESULTS:
      Analysis of precision in the continuation phase indicated that athletes performed
      significantly better than musicians and controls in the circle-drawing task,
      whereas musicians were more precise than controls in the finger tapping task.
      Interestingly, musicians were also more precise than controls in the circle
      drawing task. RESULTS also showed that the timing mode adopted was dependent on
      expertise and the presence of auditory feedback. DISCUSSION: RESULTS showed that
      movement-based expertise is associated with enhanced timing, but these effects
      depend on the nature of the training. Expertise was found to influence the timing
      strategy adopted to maintain precise rhythmic movements, suggesting that event
      and emergent timing mechanisms are not strictly tied to specific tasks, but can
      both be adopted to achieve precise timing.

PMID- 25566155
TI  - Priming determinist beliefs diminishes implicit (but not explicit) components of
      self-agency.
AB  - Weakening belief in the concept of free will yields pronounced effects upon
      social behavior, typically promoting selfish and aggressive over pro-social and
      helping tendencies. Belief manipulations have furthermore been shown to modulate
      basic and unconscious processes involved in motor control and self-regulation.
      Yet, to date, it remains unclear how high-level beliefs can impact such a wide
      range of behaviors. Here, we tested the hypothesis that priming disbelief in free
      will diminishes the sense of agency, i.e., the intrinsic sensation of being in
      control of one's own actions. To this end, we measured participants' implicit and
      explicit self-agency under both anti-free will and control conditions. Priming
      disbelief in free will reduced implicit but not explicit components of agency.
      These findings suggest that free will beliefs have a causal impact on the pre
      reflective feeling of being in control of one's actions, and solidify previous
      proposals that implicit and explicit agency components tap into distinct facets
      of action awareness. 

PMID- 25566156
TI  - Expertise among professional magicians: an interview study.
AB  - The purpose of the present investigation was to analyse interviews of highly
      regarded Finnish magicians. Social network analysis (N = 120) was used to
      identify Finland's most highly regarded magicians (N = 16). The selected
      participants' careers in professional magic and various aspects of their
      professional conduct were examined by relying on semi-structured interviews. The
      results revealed that cultivation of professional level competence in magic
      usually requires an extensive period of time compared with other domains of
      expertise. Magic is a unique performing art and it differs from other professions
      focusing on deceiving the audience. A distinctive feature of magical expertise is
      that the process takes place entirely through informal training supported by
      communities of magical practitioners. Three interrelated aspects of magical
      activity were distinguished: magic tricks, performance, and audience. Although
      magic tricks constitute a central aspect of magic activity, the participants did
      not talk about their tricks extensively; this is in accordance with the secretive
      nature of magic culture. The interviews revealed that a core aspect of the
      magicians' activity is performance in front of an audience that repeatedly
      validates competence cultivated through years of practice. The interviewees
      reported investing a great deal of effort in planning, orchestrating, and
      reflecting on their performances. Close interaction with the audience plays an
      important role in most interviewees' activity. Many participants put a great deal
      of effort in developing novel magic tricks. It is common to borrow magic effects
      from fellow magicians and develop novel methods of implementation. Because magic
      tricks or programs are not copyrighted, many interviewees considered "stealing"
      an unacceptable and unethical aspect of magical activity. The interviewees
      highlighted the importance of personality and charisma in the successful pursuit
      of magic activity. 

PMID- 25566157
TI  - Explaining the abundance of distant analogies in naturalistic observations of
      experts.

PMID- 25566159
TI  - Memory performance on the Auditory Inference Span Test is independent of
      background noise type for young adults with normal hearing at high speech
      intelligibility.
AB  - Listening in noise is often perceived to be effortful. This is partly because
      cognitive resources are engaged in separating the target signal from background
      noise, leaving fewer resources for storage and processing of the content of the
      message in working memory. The Auditory Inference Span Test (AIST) is designed to
      assess listening effort by measuring the ability to maintain and process heard
      information. The aim of this study was to use AIST to investigate the effect of
      background noise types and signal-to-noise ratio (SNR) on listening effort, as a
      function of working memory capacity (WMC) and updating ability (UA). The AIST was
      administered in three types of background noise: steady-state speech-shaped
      noise, amplitude modulated speech-shaped noise, and unintelligible speech. Three
      SNRs targeting 90% speech intelligibility or better were used in each of the
      three noise types, giving nine different conditions. The reading span test
      assessed WMC, while UA was assessed with the letter memory test. Twenty young
      adults with normal hearing participated in the study. Results showed that AIST
      performance was not influenced by noise type at the same intelligibility level,
      but became worse with worse SNR when background noise was speech-like.
      Performance on AIST also decreased with increasing memory load level.
      Correlations between AIST performance and the cognitive measurements suggested
      that WMC is of more importance for listening when SNRs are worse, while UA is of
      more importance for listening in easier SNRs. The results indicated that in young
      adults with normal hearing, the effort involved in listening in noise at high
      intelligibility levels is independent of the noise type. However, when noise is
      speech-like and intelligibility decreases, listening effort increases, probably
      due to extra demands on cognitive resources added by the informational masking
      created by the speech fragments and vocal sounds in the background noise. 

PMID- 25566158
TI  - Meditation reduces pain-related neural activity in the anterior cingulate cortex,
      insula, secondary somatosensory cortex, and thalamus.
AB  - Recent studies have shown that meditation inhibits or relieves pain perception.
      To clarify the underlying mechanisms for this phenomenon, neuroimaging methods,
      such as functional magnetic resonance imaging, and neurophysiological methods,
      such as magnetoencephalography and electroencephalography, have been used.
      However, it has been difficult to interpret the results, because there is some
      paradoxical evidence. For example, some studies reported increased neural
      responses to pain stimulation during meditation in the anterior cingulate cortex
      (ACC) and insula, whereas others showed a decrease in these regions. There have
      been inconsistent findings to date. Moreover, in general, since the activities of
      the ACC and insula are correlated with pain perception, the increase in neural
      activities during meditation would be related to the enhancement of pain
      perception rather than its reduction. These contradictions might directly
      contribute to the 'mystery of meditation.' In this review, we presented previous
      findings for brain regions during meditation and the anatomical changes that
      occurred in the brain with long-term meditation training. We then discussed the
      findings of previous studies that examined pain-related neural activity during
      meditation. We also described the brain mechanisms responsible for pain relief
      during meditation, and possible reasons for paradoxical evidence among previous
      studies. By thoroughly overviewing previous findings, we hypothesized that
      meditation reduces pain-related neural activity in the ACC, insula, secondary
      somatosensory cortex, and thalamus. We suggest that the characteristics of the
      modulation of this activity may depend on the kind of meditation and/or number of
      years of experience of meditation, which were associated with paradoxical
      findings among previous studies that investigated pain-related neural activities
      during meditation. 

PMID- 25566161
TI  - Toddlers infer unobserved causes for spontaneous events.
AB  - Previous research suggests that children infer the presence of unobserved causes
      when objects appear to move spontaneously. Are such inferences limited to motion
      events or do children assume that unexplained physical events have causes more
      generally? Here we introduce an apparently spontaneous event and ask whether,
      even in the absence of spatiotemporal and co-variation cues linking the events,
      toddlers treat a plausible variable as a cause of the event. Toddlers (24 months)
      saw a toy that appeared to light up either spontaneously or after an
      experimenter's action. Toddlers were also introduced to a button but were not
      shown any predictive relation between the button and the light. Across three
      different dependent measures of exploration, predictive looking (Study 1),
      prompted intervention (Study 2), and spontaneous exploration (Study 3), toddlers
      were more likely to represent the button as a cause of the light when the event
      appeared to occur spontaneously. In Study 4, we found that even in the absence of
      a plausible candidate cause, toddlers engaged in selective exploration when the
      light appeared to activate spontaneously. These results suggest that toddlers'
      exploration is guided by the causal explanatory power of events. 

PMID- 25566160
TI  - Children with dyslexia show cortical hyperactivation in response to increasing
      literacy processing demands.
AB  - This fMRI study aimed to examine how differences in literacy processing demands
      may affect cortical activation patterns in 11- to 12-year-old children with
      dyslexia as compared to children with typical reading skills. Eleven children
      with and 18 without dyslexia were assessed using a reading paradigm based on
      different stages of literacy development. In the analyses, six regions showed an
      interaction effect between group and condition in a factorial ANOVA. These
      regions were selected as regions of interest (ROI) for further analyses. Overall,
      the dyslexia group showed cortical hyperactivation compared to the typical group.
      The difference between the groups tended to increase with increasing processing
      demands. Differences in cortical activation were not reflected in in-scanner
      reading performance. The six regions further grouped into three patterns, which
      are discussed in terms of processing demands, compensatory mechanisms,
      orthography and contextual facilitation. We conclude that the observed
      hyperactivation is chiefly a result of compensatory activity, modulated by other
      factors. 

PMID- 25566163
TI  - An introduction to "Sugar and spice, and everything nice: exploring prosocial
      development through infancy and early childhood".

PMID- 25566162
TI  - Cortical response of the ventral attention network to unattended angry facial
      expressions: an EEG source analysis study.
AB  - INTRODUCTION: We used an affective prime task composed of emotional (happy,
      angry, and neutral) prime faces and target words with either positive or negative
      valence. By asking subjects to attend to either the faces' emotional expression
      or to the glasses' shape, we assessed whether angry facial expressions were
      processed when they were unattended and task-irrelevant. METHODS: We conducted a
      distributed source analysis on the corresponding event-related potentials focused
      on the early activity of face processing and attention networks' related areas.
      We also evaluated the magnitude of the affective priming effect. RESULTS: We
      observed a reduction of occipitotemporal areas' (BA37) activation to unattended
      compared to attended faces and a modulation of primary visual areas' activity
      lateralization. The latter was more right lateralized for attended than for
      unattended faces, and emotional faces were more right lateralized than neutral
      ones only in the former condition. Affective priming disappeared when emotional
      expressions of prime faces were ignored. Moreover, an increased activation in the
      right temporo-parietal junction (TPJ), but not in the intraparietal sulcus, was
      observed only for unattended angry facial expressions at ~170 ms after face
      presentation. CONCLUSION: We suggest that attentional resources affect the early
      processing in visual and occipito-temporal areas, irrespective of the faces'
      threatening content. The disappearance of the affective priming effect suggests
      that when subjects were asked to focus on glasses' shape, attentional resources
      were not available to process the facial emotional expression, even though
      emotion-relevant and emotion-irrelevant features of the face were presented in
      the same position. On the other hand, unattended angry faces evoked a pre
      attentive TPJ activity, which most likely represents a bottom-up trigger that
      signals their high behavioral relevance, although it is unrelated to task
      demands.

PMID- 25566164
TI  - Cognitive function and nonfood-related impulsivity in post-bariatric surgery
      patients.
AB  - Initial evidence that cognitive function improves after bariatric surgery exists.
      The post-surgery increase in cognitive control might correspond with a decrease
      of impulsive symptoms after surgery. The present study investigated cognitive
      function and nonfood-related impulsivity in patients with substantial weight loss
      due to bariatric surgery by using a comparative cross-sectional design. Fifty
      post-bariatric surgery patients (postBS group) who had significant percent weight
      loss (M = 75.94, SD = 18.09) after Roux-en-Y gastric bypass (body mass index, BMI
      M post = 30.54 kg/m(2), SDpost = 5.14) were compared with 50 age and gender
      matched bariatric surgery candidates (preBS group; BMI M pre = 48.01 kg/m(2),
      SDpre = 6.56). To measure cognitive function the following computer-assisted
      behavioral tasks were utilized: Iowa Gambling Task, Tower of Hanoi, Stroop Test,
      Trail Making Test-Part B, and Corsi Block Tapping Test. Impulsive symptoms and
      behaviors were assessed using impulsivity questionnaires and a structured
      interview for impulse control disorders (ICDs). No group differences were found
      with regard to performance-based cognitive control, self-reported impulsive
      symptoms, and ICDs. The results indicate that the general tendency to react
      impulsively does not differ between pre-surgery and post-surgery patients. The
      question of whether nonfood-related impulsivity in morbidly obese patients
      changes post-surgery should be addressed in longitudinal studies given that
      impulsive symptoms can be considered potential targets for pre- as well post
      surgery interventions. 

PMID- 25566166
TI  - Why sprint interval training is inappropriate for a largely sedentary population.

PMID- 25566165
TI  - Hearing and music in unilateral spatial neglect neuro-rehabilitation.
AB  - Unilateral spatial neglect (USN) is an attention deficit in the contralesional
      side of space which occurs after a cerebral stroke, mainly located in the right
      hemisphere. USN patients are disabled in all daily activities. USN is an
      important negative prognostic factor of functional recovery and of socio
      professional reinsertion. Thus, patient rehabilitation is a major challenge. As
      this deficit has been described in many sensory modalities (including hearing),
      many sensory and poly-sensory rehabilitation methods have been proposed to USN
      patients. They are mainly based on visual, tactile modalities and on motor
      abilities. However, these methods appear to be quite task-specific and difficult
      to transfer to functional activities. Very few studies have focused on the
      hearing modality and even fewer studies have been conducted in music as a way of
      improving spatial attention. Therefore, more research on such retraining needs is
      neccessary in order to make reliable conclusions on its efficiency in long-term
      rehabilitation. Nevertheless, some evidence suggests that music could be a
      promising tool to enhance spatial attention and to rehabilitate USN patients. In
      fact, music is a material closely linked to space, involving common anatomical
      and functional networks. The present paper aims firstly at briefly reviewing the
      different procedures of sensory retraining proposed in USN, including auditory
      retraining, and their limits. Secondly, it aims to present the recent scientific
      evidence that makes music a good candidate for USN patients' neuro
      rehabilitation. 

PMID- 25566168
TI  - Varieties of male-sexual-identity development in clinical practice: a
      neuropsychoanalytic model.
AB  - Variations of sexual identity development are present in all cultures, as well as
      in many animal species. Freud - founding father of psychoanalysis - believed that
      all men have an inherited, bisexual disposition, and that many varieties of love
      and desire are experienced as alternative pathways to intimacy. In the
      neuropsychoanalytic model, psychic development starts with the constitutional
      self. The constitutional self is comprised of the neurobiological factors which
      contribute to sexual identity development. These neurobiological factors are
      focused on biphasic sexual organization in the prenatal phase, based on
      variations in genes, sex hormones, and brain circuits. This psychosocial
      construction of sexual identity is determined through contingent mirroring by the
      parents and peers of the constitutional self. The development of the self-or
      personal identity-is linked with the development of sexual identity, gender-role
      identity, and procreative identity. Incongruent mirroring of the constitutional
      self causes alienation in the development of the self. Such alienation can be
      treated within the psychoanalytic relationship. This article presents a
      contemporary, neuropsychoanalytic, developmental theory of male-sexual identity
      relating to varieties in male-sexual-identity development, with implications for
      psychoanalytic treatment, and is illustrated with three vignettes from clinical
      practice. 

PMID- 25566167
TI  - Direct cost does not impact on young children's spontaneous helping behavior.
AB  - The propensity of humans to engage in prosocial behavior is unlike that of any
      other species. Individuals will help others even when it comes at a cost to
      themselves, and even when the others are complete strangers. However, to date,
      scant empirical evidence has been forthcoming on young children's altruistic
      tendencies. To investigate this 45 4-year-olds were presented with a task in
      which they had opportunity to help an adult confederate retrieve a reward from a
      novel box. In a control condition children were given no information about the
      effect of potential helping behavior. Alternatively they were informed that
      helping would either cost them (i.e., they would miss out on getting the reward)
      or benefit them (i.e., they would get the reward). It was hypothesized that
      children would be less likely, and slower, to help in the cost condition,
      compared to the other two conditions. This hypothesis was not supported: children
      across all conditions provided help at near ceiling levels. 

PMID- 25566169
TI  - Exposure to trauma-relevant pictures is associated with tachycardia in victims
      who had experienced an intense peritraumatic defensive response: the tonic
      immobility.
AB  - Tonic immobility is an involuntary, last-ditch defensive reaction characterized
      by physical inactivity in a context of inescapable threat that has been described
      in many species, including humans. The occurrence of this defensive response is a
      predictor of the severity of psychiatric disorders and may be considered as an
      index of an intense reaction to a traumatic event. Here, we investigated whether
      the retrospective reports of peritraumatic tonic immobility reaction in
      participants exposed to a traumatic event would modify their cardiac responses to
      pictures related to their trauma. Using a questionnaire of life-threating events,
      we selected students who experienced violent crime as their most intense trauma
      and students who had never experienced a violent crime trauma, but experienced
      other traumatic events. All participants completed a questionnaire that estimated
      the intensity of tonic immobility during their most intense trauma.
      Electrocardiographic recordings were collected during exposure to pictures.
      Participants viewed emotional pictures (human attack with guns) and neutral
      pictures. These emotional stimuli were selected to be trauma-relevant to the
      violent crime group and non trauma-relevant to the no violent crime trauma group.
      Violent crime group showed a positive correlation between heart rate changes
      after viewing trauma-related pictures and tonic immobility scores. We observed
      that low tonic immobility scores were associated with bradycardia and high scores
      with tachycardia in response to trauma-relevant pictures. For the no violent
      crime group, no significant correlation was detected. These results suggest that
      the relevance of the stimuli and the magnitude of the defensive response during a
      previous trauma event were important factors triggering more intense defensive
      responses. 

PMID- 25566172
TI  - Accompanying Symptoms Overlap during Attacks in Meniere's Disease and Vestibular
      Migraine.
AB  - Meniere's disease and vestibular migraine (VM) are the most common causes of
      spontaneous recurrent vertigo. The current diagnostic criteria for the two
      disorders are mainly based on patients' symptoms, and no biological marker is
      available. When applying these criteria, an overlap of the two disorders is
      occasionally observed in clinical practice. Therefore, the present prospective
      multicenter study aimed to identify accompanying symptoms that may help to
      differentiate between MD, VM, and probable vestibular migraine (pVM). Two hundred
      and sixty-eight patients were included in the study (MD: n = 119, VM: n = 84,
      pVM: n = 65). Patients with MD suffered mainly from accompanying auditory
      symptoms (tinnitus, fullness of ear, and hearing loss), while accompanying
      migraine symptoms (migraine-type headache, photo-/phonophobia, visual aura),
      anxiety, and palpitations were more common during attacks of VM. However, it has
      to be noted that a subset of MD patients also experienced (migraine-type)
      headache during the attacks. On the other hand, some VM/pVM patients reported
      accompanying auditory symptoms. The female/male ratio was statistically higher in
      VM/pVM as compared to MD, while the age of onset was significantly lower in the
      former two. The frequency of migraine-type headache was significantly higher in
      VM as compared to both pVM and MD. Accompanying headache of any type was observed
      in declining order in VM, pVM, and MD. In conclusion, the present study confirms
      a considerable overlap of symptoms in MD, VM, and pVM. In particular, we could
      not identify any highly specific symptom for one of the three entities. It is
      rather the combination of symptoms that should guide diagnostic reasoning. The
      identification of common symptom patterns in VM and MD may help to refine future
      diagnostic criteria for the two disorders. 

PMID- 25566171
TI  - The representation of inflammatory signals in the brain - a model for subjective
      fatigue in multiple sclerosis.
AB  - In multiple sclerosis (MS) patients, fatigue is rated as one of the most common
      and disabling symptoms. However, the pathophysiology underlying this fatigue is
      not yet clear. Several lines of evidence suggest that immunological factors, such
      as elevated levels of pro-inflammatory cytokines, may contribute to subjective
      fatigue in MS patients. Pro-inflammatory cytokines represent primary mediators of
      immune-to-brain-communication, modulating changes in the neurophysiology of the
      central nervous system. Recently, we proposed a model arguing that fatigue in MS
      patients is a subjective feeling, which is related to inflammation. Moreover, it
      implies that fatigue can be measured behaviorally only by applying specific
      cognitive tasks related to alertness and vigilance. In the present review, we
      focus on the subjective feeling of MS-related fatigue. We examine the hypothesis
      that the subjective feeling of MS-related fatigue may be a variant of
      inflammation-induced sickness behavior, resulting from cytokine-mediated activity
      changes within brain areas involved in interoception and homeostasis including
      the insula, the anterior cingulate, and the hypothalamus. We first present
      studies demonstrating a relationship between pro-inflammatory cytokines and
      subjective fatigue in healthy individuals, in people with inflammatory disorders,
      and particularly in MS patients. Subsequently, we discuss studies analyzing the
      impact of anti-inflammatory treatment on fatigue. In the next part of this
      review, we present studies on the transmission and neural representation of
      inflammatory signals, with a special focus on possible neural concomitants of
      inflammation-induced fatigue. We also present two of our studies on the
      relationship between local gray and white matter atrophy and fatigue in MS
      patients. Finally, we discuss some implications of our findings and future
      perspectives. 

PMID- 25566170
TI  - Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate,
      and the Therapeutic Implications.
AB  - The dopamine (DA) precursor l-DOPA has been the most effective treatment for
      Parkinson's disease (PD) for over 40 years. However, the response to this
      treatment changes with disease progression, and most patients develop dyskinesias
      (abnormal involuntary movements) and motor fluctuations within a few years of l
      DOPA therapy. There is wide consensus that these motor complications depend on
      both pre- and post-synaptic disturbances of nigrostriatal DA transmission.
      Several presynaptic mechanisms converge to generate large DA swings in the brain
      concomitant with the peaks-and-troughs of plasma l-DOPA levels, while post
      synaptic changes engender abnormal functional responses in dopaminoceptive
      neurons. While this general picture is well-accepted, the relative contribution
      of different factors remains a matter of debate. A particularly animated debate
      has been growing around putative players on the presynaptic side of the cascade.
      To what extent do presynaptic disturbances in DA transmission depend on
      deficiency/dysfunction of the DA transporter, aberrant release of DA from
      serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is
      synthetized from DA) play a role? This review article will summarize key
      findings, controversies, and pending questions regarding the presynaptic
      mechanisms of l-DOPA-induced dyskinesia. Intriguingly, the debate around these
      mechanisms has spurred research into previously unexplored facets of brain
      plasticity that have far-reaching implications to the treatment of
      neuropsychiatric disease. 

PMID- 25566173
TI  - The influence of environmental factors on sleep quality in hospitalized medical
      patients.
AB  - INTRODUCTION: Sleep-wake disturbances are common in hospitalized patients but few
      studies have assessed them systematically. The aim of the present study was to
      assess sleep quality in a group of medical inpatients, in relation to
      environmental factors, and the switch to daylight-saving time. METHODS: Between
      March and April 2013, 118 consecutive inpatients were screened and 99 (76 +/- 11
      years; hospitalization: 8 +/- 7 days) enrolled. They slept in double or quadruple
      rooms, facing South/South-East, and were qualified as sleeping near/far from the
      window. They underwent daily sleep assessment by standard questionnaires/diaries.
      Illuminance was measured by a luxmeter at each patient's eye-level, four times
      per day. Noise was measured at the same times by a phonometer. Information was
      recorded on room lighting, position of the rolling shutters and number/type of
      extra people in the room. RESULTS: Compliance with sleep-wake assessment was
      poor, with a range of completion of 2-59%, depending on the questionnaires.
      Reported sleep quality was sufficient and sleep timing dictated by hospital
      routine; 33% of the patients reported one/more sleepless nights. Illuminance was
      generally low, and rolling shutters half-way down for most of the 24 h. Patients
      who slept near the window were exposed to more light in the morning (i.e., 222 +/
      72 vs. 174 +/- 85 lux, p < 0.05 before the switch; 198 +/- 72 vs. 141 +/- 137
      lux, p < 0.01 after the switch) and tended to sleep better (7.3 +/- 1.8 vs. 5.8
      +/- 2.4 on a 1-10 scale, before the switch, p < 0.05; 7.7 +/- 2.3 vs. 6.6 +/-
      1.8, n.s. after the switch). Noise levels were higher than recommended for care
      units but substantially comparable across times/room types. No significant
      differences were observed in sleep parameters before/after the switch.
      CONCLUSION: Medical wards appear to be noisy environments, in which limited
      attention is paid to light/dark hygiene. An association was observed between
      sleep quality and bed position/light exposure, which is worthy of further study.

PMID- 25566176
TI  - Refractory Fulminant Acute Disseminated Encephalomyelitis (ADEM) in an Adult.
AB  - Acute disseminated encephalomyelitis (ADEM) is characterized by its rapid
      progression with variable symptoms and severity in adults and children. Multiple
      therapeutic options have been proposed, but solid evidence is yet to be gathered.
      We describe an adult man with a fulminant form of ADEM unresponsive to numerous
      treatment modalities. 

PMID- 25566174
TI  - Control of abnormal synchronization in neurological disorders.
AB  - In the nervous system, synchronization processes play an important role, e.g., in
      the context of information processing and motor control. However, pathological,
      excessive synchronization may strongly impair brain function and is a hallmark of
      several neurological disorders. This focused review addresses the question of how
      an abnormal neuronal synchronization can specifically be counteracted by invasive
      and non-invasive brain stimulation as, for instance, by deep brain stimulation
      for the treatment of Parkinson's disease, or by acoustic stimulation for the
      treatment of tinnitus. On the example of coordinated reset (CR) neuromodulation,
      we illustrate how insights into the dynamics of complex systems contribute to
      successful model-based approaches, which use methods from synergetics, non-linear
      dynamics, and statistical physics, for the development of novel therapies for
      normalization of brain function and synaptic connectivity. Based on the intrinsic
      multistability of the neuronal populations induced by spike timing-dependent
      plasticity (STDP), CR neuromodulation utilizes the mutual interdependence between
      synaptic connectivity and dynamics of the neuronal networks in order to restore
      more physiological patterns of connectivity via desynchronization of neuronal
      activity. The very goal is to shift the neuronal population by stimulation from
      an abnormally coupled and synchronized state to a desynchronized regime with
      normalized synaptic connectivity, which significantly outlasts the stimulation
      cessation, so that long-lasting therapeutic effects can be achieved. 

PMID- 25566178
TI  - Low consistency of four brain connectivity measures derived from intracranial
      electrode measurements.
AB  - Measures of brain connectivity are currently subject to intense scientific and
      clinical interest. Multiple measures are available, each with advantages and
      disadvantages. Here, we study epilepsy patients with intracranial electrodes, and
      compare four different measures of connectivity. Perhaps the most direct measure
      derives from intracranial electrodes; however, this is invasive and spatial
      coverage is incomplete. These electrodes can be actively stimulated to trigger
      electrophysical responses to provide the first measure of connectivity. A second
      measure is the recent development of simultaneous BOLD fMRI and intracranial
      electrode stimulation. The resulting BOLD maps form a measure of effective
      connectivity. A third measure uses low frequency BOLD fluctuations measured by
      MRI, with functional connectivity defined as the temporal correlation coefficient
      between their BOLD waveforms. A fourth measure is structural, derived from
      diffusion MRI, with connectivity defined as an integrated diffusivity measure
      along a connecting pathway. This method addresses the difficult requirement to
      measure connectivity between any two points in the brain, reflecting the
      relatively arbitrary location of the surgical placement of intracranial
      electrodes. Using a group of eight epilepsy patients with intracranial
      electrodes, the connectivity from one method is compared to another method using
      all paired data points that are in common, yielding an overall correlation
      coefficient. This method is performed for all six paired-comparisons between the
      four methods. While these show statistically significant correlations, the
      magnitudes of the correlation are relatively modest (r (2) between 0.20 and
      0.001). In summary, there are many pairs of points in the brain that correlate
      well using one measure yet correlate poorly using another measure. These
      experimental findings present a complicated picture regarding the measure or
      meaning of brain connectivity. 

PMID- 25566180
TI  - Predictive factors of neurological complications and one-month mortality after
      liver transplantation.
AB  - BACKGROUND: Neurological complications are common after orthotopic liver
      transplantation (OLT). We aimed to characterize the risk factors associated with
      neurological complications and mortality among patients who underwent OLT in the
      post-model for end-stage liver disease (MELD) era. METHODS: In a retrospective
      review, we evaluated 227 consecutive patients at the Keck Hospital of the
      University of Southern California before and after OLT to define the type and
      frequency of and risk factors for neurological complications and mortality.
      RESULTS: Neurological complications were common (n = 98), with encephalopathy
      being most frequent (56.8%), followed by tremor (26.5%), hallucinations (11.2%),
      and seizure (8.2%). Factors associated with neurological complications after OLT
      included preoperative dialysis, hepatorenal syndrome, renal insufficiency, intra
      operative dialysis, preoperative encephalopathy, preoperative mechanical
      ventilation, and infection. Preoperative infection was an independent predictor
      of neurological complications (OR 2.83, 1.47-5.44). One-month mortality was 8.8%
      and was independently associated with urgent re-transplant, preoperative
      intubation, and intra-operative arrhythmia. CONCLUSION: Neurological
      complications are common in patients undergoing OLT in the post-MELD era, with
      encephalopathy being most frequent. An improved understanding of the risk factors
      related to both neurological complications and one-month mortality post
      transplantation can better guide perioperative care and help improve outcomes
      among OLT patients.

PMID- 25566181
TI  - Amyloid Beta, TNFalpha and FAIM-L; Approaching New Therapeutic Strategies for AD.

PMID- 25566179
TI  - UCH-L1 and GFAP Serum Levels in Neonates with Hypoxic-Ischemic Encephalopathy: A
      Single Center Pilot Study.
AB  - OBJECTIVE: We examined two potential biomarkers of brain damage in hypoxic
      ischemic encephalopathy (HIE) neonates: glial fibrillary acidic protein (GFAP; a
      marker of gliosis) and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of
      neuronal injury). We hypothesized that the biomarkers would be measurable in cord
      blood of healthy neonates and could serve as a normative reference for brain
      injury in HIE infants. We further hypothesized that higher levels would be
      detected in serum samples of HIE neonates and would correlate with brain damage
      on magnetic resonance imaging (MRI) and later developmental outcomes.? STUDY
      DESIGN: Serum UCH-L1 and GFAP concentrations from HIE neonates (n = 16) were
      compared to controls (n = 11). The relationship between biomarker concentrations
      of HIE neonates and brain damage (MRI) and developmental outcomes (Bayley-III)
      was examined using Pearson correlation coefficients and a mixed model design.
      RESULT: Both biomarkers were detectable in cord blood from control subjects. UCH
      L1 concentrations were higher in HIE neonates (p < 0.001), and associated with
      cortical injury (p < 0.055) and later motor and cognitive developmental outcomes
      (p < 0.05). The temporal change in GFAP concentrations during (from birth to 96 h
      of age) predicted motor developmental outcomes (p < 0.05) and injury to the basal
      ganglia and white matter. CONCLUSION: Ubiquitin C-terminal hydrolase L1 and GFAP
      should be explored further as promising serum biomarkers of brain damage and
      later neurodevelopmental outcomes in neonates with HIE.

PMID- 25566177
TI  - Tinnitus what and where: an ecological framework.
AB  - Tinnitus is an interaction of the environment, cognition, and plasticity. The
      connection between the individual with tinnitus and their world seldom receives
      attention in neurophysiological research. As well as changes in cell
      excitability, an individual's culture and beliefs, and work and social environs
      may all influence how tinnitus is perceived. In this review, an ecological
      framework for current neurophysiological evidence is considered. The model
      defines tinnitus as the perception of an auditory object in the absence of an
      acoustic event. It is hypothesized that following deafferentation: adaptive
      feature extraction, schema, and semantic object formation processes lead to
      tinnitus in a manner predicted by Adaptation Level Theory (1, 2). Evidence from
      physiological studies is compared to the tenants of the proposed ecological
      model. The consideration of diverse events within an ecological context may unite
      seemingly disparate neurophysiological models. 

PMID- 25566182
TI  - Sleep Strategies of Night-Shift Nurses on Days Off: Which Ones are Most Adaptive?
AB  - OBJECTIVES: To determine the off-shift sleep strategies of bi-ethnic night-shift
      nurses, the relationship between these sleep strategies and adaptation to shift
      work, and identify the participant-level characteristics associated with a given
      sleep strategy. METHODS: African-American and non-Hispanic White female, night
      shift nurses from an academic hospital were recruited to complete a survey on
      sleep-wake patterns (n = 213). Participants completed the standard shiftwork
      index and the biological clocks questionnaire to determine sleep strategies and
      adaptation to night-shift work. In addition, chronotype was determined
      quantitatively with a modified version of the Munich ChronoType Questionnaire.
      Most participants worked ~3 consecutive 12-h night-shifts followed by several
      days off. RESULTS: Five sleep strategies used on days off were identified: (a)
      night stay, (b) nap proxy, (c) switch sleeper, (d) no sleep, and (e) incomplete
      switcher. Nap proxy and no sleep types were associated with poorer adaptation to
      night-shift work. The switch sleeper and incomplete switcher types were
      identified as more adaptive strategies that were associated with less sleep
      disturbance, a later chronotype, and less cardiovascular problems. CONCLUSION:
      Behavioral sleep strategies are related to adaptation to a typical night-shift
      schedule among hospital nurses. Nurses are crucial to the safety and well-being
      of their patients. Therefore, adoption of more adaptive sleep strategies may
      reduce sleep/wake dysregulation in this population, and improve cardiovascular
      outcomes.

PMID- 25566175
TI  - Effects of low-level blast exposure on the nervous system: is there really a
      controversy?
AB  - High-pressure blast waves can cause extensive CNS injury in human beings.
      However, in combat settings, such as Iraq and Afghanistan, lower level exposures
      associated with mild traumatic brain injury (mTBI) or subclinical exposure have
      been much more common. Yet controversy exists concerning what traits can be
      attributed to low-level blast, in large part due to the difficulty of
      distinguishing blast-related mTBI from post-traumatic stress disorder (PTSD). We
      describe how TBI is defined in human beings and the problems posed in using
      current definitions to recognize blast-related mTBI. We next consider the problem
      of applying definitions of human mTBI to animal models, in particular that TBI
      severity in human beings is defined in relation to alteration of consciousness at
      the time of injury, which typically cannot be assessed in animals. However, based
      on outcome assessments, a condition of "low-level" blast exposure can be defined
      in animals that likely approximates human mTBI or subclinical exposure. We review
      blast injury modeling in animals noting that inconsistencies in experimental
      approach have contributed to uncertainty over the effects of low-level blast.
      Yet, animal studies show that low-level blast pressure waves are transmitted to
      the brain. In brain, low-level blast exposures cause behavioral, biochemical,
      pathological, and physiological effects on the nervous system including the
      induction of PTSD-related behavioral traits in the absence of a psychological
      stressor. We review the relationship of blast exposure to chronic
      neurodegenerative diseases noting the paradoxical lowering of Abeta by blast,
      which along with other observations suggest that blast-related TBI is
      pathophysiologically distinct from non-blast TBI. Human neuroimaging studies show
      that blast-related mTBI is associated with a variety of chronic effects that are
      unlikely to be explained by co-morbid PTSD. We conclude that abundant evidence
      supports low-level blast as having long-term effects on the nervous system. 

PMID- 25566183
TI  - Difference in Motor Fatigue between Patients with Stroke and Patients with
      Multiple Sclerosis: A Pilot Study.
AB  - Fatigue is often reported in stroke patients. However, it is still unclear if
      fatigue in stroke patients is more prominent, more frequent or more "typical"
      than in patients with multiple sclerosis (MS) and if the pathophysiology differs
      between these two populations. The purpose of this study was to compare motor
      fatigue and fatigue-induced changes in kinematic gait parameters between stroke
      patients, MS patients, and healthy persons. Gait parameters at the beginning and
      end of a treadmill walking test were assessed in 10 stroke patients, 40 MS
      patients, and 20 healthy subjects. The recently developed Fatigue index Kliniken
      Schmieder (FKS) based on change of the movement's attractor and its variability
      was used to measure motor fatigue. Six stroke patients had a pathological FKS.
      The FKS (indicating the level of motor fatigue) in stroke patients was similar
      compared to MS patients. Stroke patients had smaller step length, step height and
      greater step width, circumduction with the right and left leg, and greater sway
      compared to the other groups at the beginning and at the end of test. A severe
      walking impairment in stroke patients does not necessarily cause a pathological
      FKS indicating motor fatigue. Moreover, the FKS can be used as a measure of motor
      fatigue in stroke and MS and may also be applicable to other diseases. 

PMID- 25566184
TI  - Structural analysis of how podocytes detach from the glomerular basement membrane
      under hypertrophic stress.
AB  - Podocytes are lost by detachment from the GBM as viable cells; details are
      largely unknown. We studied this process in the rat after growth stimulation with
      FGF-2. Endothelial and mesangial cells responded by hyperplasia, podocytes
      underwent hypertrophy, but, in the long run, developed various changes that could
      either be interpreted showing progressing stages in detachment from the GBM or
      stages leading to a tighter attachment by foot process effacement (FPE). This
      occurred in microdomains within the same podocyte; thus, features of detachment
      and of reinforced attachment may simultaneously be found in the same podocyte.
      (1) Initially, hypertrophied podocytes underwent cell body attenuation and formed
      large pseudocysts, i.e., expansions of the subpodocyte space. (2) Podocytes
      entered the process of FPE starting with the retraction of foot processes (FPs)
      and the replacement of the slit diaphragm by occluding junctions, thereby sealing
      the filtration slits. Successful completion of this process led to broad
      attachments of podocyte cell bodies to the GBM. (3) Failure of sealing the slits
      led to gaps of varying width between retracting FPs facilitating the outflow of
      the filtrate from the GBM. (4) Since those gaps are frequently overarched by
      broadened primary processes, the drainage of the filtrate into the Bowman's space
      may be hindered leading to the formation of small pseudocysts associated with
      bare areas of GBM. (5) The merging of pseudocysts created a system of
      communicating chambers through which the filtrate has to pass to reach Bowman's
      space. Multiple flow resistances in series likely generated an expansile force on
      podocytes contributing to detachment. (6) Such a situation appears to proceed to
      complete disconnection generally of a group of podocytes owing to the junctional
      connections between them. (7) Since such groups of detaching podocytes generally
      make contact to parietal cells, they start the formation of tuft adhesions to
      Bowman's capsule. 

PMID- 25566185
TI  - The podocyte power-plant disaster and its contribution to glomerulopathy.
AB  - Proper podocyte function within the glomerulus demands a high and continuous
      energy supply that is mainly derived from the respiratory chain of the inner
      mitochondrial membrane. Dysregulations in the metabolic homeostasis of podocytes
      may result in podocyte damage and glomerular disease. This article highlights the
      current knowledge about podocyte energy supply by the respiratory chain. We
      review the regulation of mitochondrial oxidative metabolism with regard to
      podocytopathy and discuss the latest understanding of different mitochondrial
      dysfunctions of the podocyte in diabetic nephropathy and focal segmental
      glomerulosclerosis (FSGS). We discuss genetic forms of mitochondriopathy of the
      podocyte and end with recent knowledge about crosstalk between NADH and NADPH and
      potential therapeutic options for podocyte mitochondriopathy. We aim to raise
      awareness for the complex and interesting mechanisms of podocyte damage by
      impaired energy supply that, despite of novel findings in recent years, is poorly
      understood so far. 

PMID- 25566186
TI  - Natriuretic hormone: the ultimate determinant of the preservation of external
      sodium balance.
AB  - The present manuscript focuses on a putative natriuretic hormone. It includes the
      history of a long-term search for the pure molecule, ranging from partial
      purification to synthesis. It includes a description of seven different bioassay
      systems used, a resume of the sequential steps in purification, and a summary of
      a series of experimental protocols employed in the effort to define the biologic
      properties of the inhibitor of sodium (Na) transport. Two closely related
      molecules were purified and synthesized. Both are xanthurenic acid derivatives
      (xanthurenic acid 8-O-beta-D-glucoside and xanthurenic acid 8-O-sulfate). It is
      concluded that one or both of these two low molecular weight compounds (MW: 368
      and 284) meet many of the criteria for the final modulator of Na excretion. 

PMID- 25566187
TI  - Type 3 deiodinase: role in cancer growth, stemness, and metabolism.
AB  - Deiodinases are selenoenzymes that catalyze thyroid hormones (THs) activation
      (type 1 and type 2, D1 and D2, respectively) or inactivation (type 3, D3). THs
      are essential for proper body development and cellular differentiation. Their
      intra- and extra-cellular concentrations are tightly regulated by deiodinases
      with a pre-receptorial control thus generating active or inactive form of THs.
      Changes in deiodinases expression are anatomically and temporally regulated and
      influence the downstream TH signaling. D3 overexpression is a feature of
      proliferative tissues such as embryo or cancer tissues. The enhanced TH
      degradation by D3 induces a local hypothyroidism, thus inhibiting THs
      transcriptional activity. Of note, overexpression of D3 is a feature of several
      highly proliferative cancers. In this paper, we review recent advances in the
      role of D3 in cancer growth, stemness, and metabolic phenotype. In particular, we
      focus on the main signaling pathways that result in the overexpression of D3 in
      cancer cells and are known to be relevant to cancer development, progression, and
      recurrence. We also discuss the potential role of D3 in cancer stem cells
      metabolic phenotype, an emerging topic in cancer research. 

PMID- 25566188
TI  - The role of calcium, lipid membranes and islet amyloid polypeptide in the onset
      of type 2 diabetes: innocent bystanders or partners in a crime?

PMID- 25566190
TI  - Evolution of hepatic steatosis to fibrosis and adenoma formation in liver
      specific growth hormone receptor knockout mice.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common
      forms of chronic liver diseases closely associated with obesity and insulin
      resistance; deficient growth hormone (GH) action in liver has been implicated as
      a mechanism. Here, we investigated the evolution of NAFLD in aged mice with liver
      specific GHR deletion. METHODS: We examined glucose tolerance, insulin
      responsiveness, and lipid profiles in aged male mice (44-50 weeks) with GHRLD. We
      performed proteomics analysis, pathway-based Superarray assay, as well as
      quantitative RT-PCR to gain molecular insight into the mechanism(s) of GHR
      deficiency-mediated NAFLD. In addition, we examined the pathological changes of
      livers of aged GHRLD male mice. RESULTS: The biochemical profile was consistent
      with that of the metabolic syndrome: abnormal glucose tolerance, impaired insulin
      secretion, and hyperlipidemia. RT-qPCR analysis of key markers of inflammation
      revealed a three- to fivefold increase in TNFalpha and CCL3, confirming the
      presence of inflammation. Expression of fibrotic markers (e.g., Col1A2 and
      Col3A1) was significantly increased, together with a two- to threefold increase
      in TGFbeta transcripts. Proteomics analyses showed a marked decrease of Mup1 and
      Selenbp2. In addition, pathway-analysis showed that the expression of cell cycle
      and growth relevant genes (i.e., Ccnd1, Socs2, Socs3, and Egfr) were markedly
      affected in GHRLD liver. Microscopic analyses (H&E) of GHRLD livers revealed the
      presence of hepatic adenomas of different stages of malignancy. CONCLUSION:
      Abrogation of GH signaling in male liver leads to metabolic syndrome, hepatic
      steatosis, increased inflammation and fibrosis, and development of hepatic tumor.
      Since obesity, a common precursor of NAFLD, is a state of deficient GH secretion
      and action, the GHRLD model could be used to unravel the contribution of
      compromised hepatic GH signaling in these pathological processes, and help to
      identify potential targets for intervention.

PMID- 25566189
TI  - Sarcopenia and Androgens: A Link between Pathology and Treatment.
AB  - Sarcopenia, the age-related loss of skeletal muscle mass and function, is
      becoming more prevalent as the lifespan continues to increase in most
      populations. As sarcopenia is highly disabling, being associated with increased
      risk of dependence, falls, fractures, weakness, disability, and death,
      development of approaches to its prevention and treatment are required. Androgens
      are the main physiologic anabolic steroid hormones and normal testosterone levels
      are necessary for a range of developmental and biological processes, including
      maintenance of muscle mass. Testosterone concentrations decline as age increase,
      suggesting that low plasma testosterone levels can cause or accelerate muscle-
      and age-related diseases, as sarcopenia. Currently, there is increasing interest
      on the anabolic properties of testosterone for therapeutic use in muscle diseases
      including sarcopenia. However, the pathophysiological mechanisms underlying this
      muscle syndrome and its relationship with plasma level of androgens are not
      completely understood. This review discusses the recent findings regarding
      sarcopenia, the intrinsic, and extrinsic mechanisms involved in the onset and
      progression of this disease and the treatment approaches that have been developed
      based on testosterone deficiency and their implications. 

PMID- 25566191
TI  - Cholecystokinin-Like Peptide (DSK) in Drosophila, Not Only for Satiety Signaling.
AB  - Cholecystokinin (CCK) signaling appears well conserved over evolution. In
      Drosophila, the CCK-like sulfakinins (DSKs) regulate aspects of gut function,
      satiety and food ingestion, hyperactivity and aggression, as well as escape
      related locomotion and synaptic plasticity during neuromuscular junction
      development. Activity in the DSK-producing neurons is regulated by octopamine. We
      discuss mechanisms behind CCK function in satiety, aggression, and locomotion in
      some detail and highlight similarities to mammalian CCK signaling. 

PMID- 25566192
TI  - Ligand-mediated endocytosis and trafficking of the insulin-like growth factor
      receptor I and insulin receptor modulate receptor function.
AB  - The insulin-like growth factor system and its two major receptors, the IGF
      receptor I (IGF-IR) and IR, plays a central role in a variety of physiological
      cellular processes including growth, differentiation, motility, and glucose
      homeostasis. The IGF-IR is also essential for tumorigenesis through its capacity
      to protect cancer cells from apoptosis. The IR is expressed in two isoforms: the
      IR isoform A (IR-A) and isoform B (IR-B). While the role of the IR-B in the
      regulation of metabolic effects has been known for several years, more recent
      evidence suggests that the IR, and in particular the IR-A, may be involved in the
      pathogenesis of cancer. Ligand-mediated endocytosis of tyrosine-kinases receptors
      plays a critical role in modulating the duration and intensity of receptors
      action but while the signaling pathways induced by the IGF-IR and IR are quite
      characterized, very little is still known about the mechanisms and proteins that
      regulate ligand-induced IGF-IR and IR endocytosis and trafficking. In addition,
      how these processes affect receptor downstream signaling has not been fully
      characterized. Here, we discuss the current understanding of the mechanisms and
      proteins regulating IGF-IR and IR endocytosis and sorting and their implications
      in modulating ligand-induced biological responses. 

PMID- 25566193
TI  - O-GlcNAc: A Bittersweet Switch in Liver.
AB  - The liver is a vital organ responsible for maintaining nutrient homeostasis.
      After a meal, insulin stimulates glycogen and lipid synthesis in the liver; in
      the fasted state, glucagon induces gluconeogenesis and ketogenesis, which produce
      glucose and ketone bodies for other tissues to use as energy sources. These
      metabolic changes involve spatiotemporally co-ordinated signaling cascades. O
      linked beta-N-acetylglucosamine (O-GlcNAc) modification has been recognized as a
      nutrient sensor and regulatory molecular switch. This review highlights
      mechanistic insights into spatiotemporal regulation of liver metabolism by O
      GlcNAc modification and discusses its pathophysiological implications in insulin
      resistance, non-alcoholic fatty liver disease, and fibrosis. 

PMID- 25566194
TI  - IGF-IR Targeted Therapy: Past, Present and Future.
AB  - The IGF-I receptor (IGF-IR) has been studied as an anti-cancer target. However,
      monotherapy trials with IGF-IR targeted antibodies or with IGF-IR specific
      tyrosine kinase inhibitors have, overall, been very disappointing in the clinical
      setting. This review discusses potential reasons why IGF-I R targeted therapy
      fails to inhibit growth of human cancers. It has become clear that intracellular
      signaling pathways are highly interconnected and complex instead of being linear
      and simple. One of the most potent candidates for failure of IGF-IR targeted
      therapy is the insulin receptor isoform A (IR-A). Activation of the IR-A by
      insulin-like growth factor-II (IGF-II) bypasses the IGF-IR and its inhibition.
      Another factor may be that anti-cancer treatment may reduce IGF-IR expression.
      IGF-IR blocking drugs may also induce hyperglycemia and hyperinsulinemia, which
      may further stimulate cell growth. In addition, circulating IGF-IRs may reduce
      therapeutic effects of IGF-IR targeted therapy. Nevertheless, it is still
      possible that the IGF-IR may be a useful adjuvant or secondary target for the
      treatment of human cancers. Development of functional inhibitors that affect the
      IGF-IR and IR-A may be necessary to overcome resistance and to make IGF-IR
      targeted therapy successful. Drugs that modify alternative downstream effects of
      the IGF-IR, so called "biasing agonists," should also be considered. 

PMID- 25566195
TI  - Dolphins and diabetes: applying one health for breakthrough discoveries.

PMID- 25566196
TI  - Microbial interactions and the ecology and evolution of Hawaiian Drosophilidae.
AB  - Adaptive radiations are characterized by an increased rate of speciation and
      expanded range of habitats and ecological niches exploited by those species. The
      Hawaiian Drosophilidae is a classic adaptive radiation; a single ancestral
      species colonized Hawaii approximately 25 million years ago and gave rise to two
      monophyletic lineages, the Hawaiian Drosophila and the genus Scaptomyza. The
      Hawaiian Drosophila are largely saprophagous and rely on approximately 40 endemic
      plant families and their associated microbes to complete development. Scaptomyza
      are even more diverse in host breadth. While many species of Scaptomyza utilize
      decomposing plant substrates, some species have evolved to become herbivores,
      parasites on spider egg masses, and exploit microbes on living plant tissue.
      Understanding the origin of the ecological diversity encompassed by these nearly
      700 described species has been a challenge. The central role of microbes in
      drosophilid ecology suggests bacterial and fungal associates may have played a
      role in the diversification of the Hawaiian Drosophilidae. Here we synthesize
      recent ecological and microbial community data from the Hawaiian Drosophilidae to
      examine the forces that may have led to this adaptive radiation. We propose that
      the evolutionary success of the Hawaiian Drosophilidae is due to a combination of
      factors, including adaptation to novel ecological niches facilitated by microbes.

PMID- 25566197
TI  - Phaeocystis antarctica blooms strongly influence bacterial community structures
      in the Amundsen Sea polynya.
AB  - Rising temperatures and changing winds drive the expansion of the highly
      productive polynyas (open water areas surrounded by sea ice) abutting the
      Antarctic continent. Phytoplankton blooms in polynyas are often dominated by the
      haptophyte Phaeocystis antarctica, and they generate the organic carbon that
      enters the resident microbial food web. Yet, little is known about how
      Phaeocystis blooms shape bacterial community structures and carbon fluxes in
      these systems. We identified the bacterial communities that accompanied a
      Phaeocystis bloom in the Amundsen Sea polynya during the austral summers of 2007
      2008 and 2010-2011. These communities are distinct from those determined for the
      Antarctic Circumpolar Current (ACC) and off the Palmer Peninsula. Diversity
      patterns for most microbial taxa in the Amundsen Sea depended on location (e.g.,
      waters abutting the pack ice near the shelf break and at the edge of the Dotson
      glacier) and depth, reflecting different niche adaptations within the confines of
      this isolated ecosystem. Inside the polynya, P. antarctica coexisted with the
      bacterial taxa Polaribacter sensu lato, a cryptic Oceanospirillum, SAR92 and
      Pelagibacter. These taxa were dominated by a single oligotype (genotypes
      partitioned by Shannon entropy analysis) and together contributed up to 73% of
      the bacterial community. Size fractionation of the bacterial community [<3 MUm
      (free-living bacteria) vs. >3 MUm (particle-associated bacteria)] identified
      several taxa (especially SAR92) that were preferentially associated with
      Phaeocystis colonies, indicative of a distinct role in Phaeocystis bloom ecology.
      In contrast, particle-associated bacteria at 250 m depth were enriched in
      Colwellia and members of the Cryomorphaceae suggesting that they play important
      roles in the decay of Phaeocystis blooms. 

PMID- 25566198
TI  - Microbial diversity and community structure across environmental gradients in
      Bransfield Strait, Western Antarctic Peninsula.
AB  - The Southern Ocean is currently subject to intense investigations, mainly related
      to its importance for global biogeochemical cycles and its alarming rate of
      warming in response to climate change. Microbes play an essential role in the
      functioning of this ecosystem and are the main drivers of the biogeochemical
      cycling of elements. Yet, the diversity and abundance of microorganisms in this
      system remain poorly studied, in particular with regards to changes along
      environmental gradients. Here, we used amplicon sequencing of 16S rRNA gene tags
      using primers covering both Bacteria and Archaea to assess the composition and
      diversity of the microbial communities from four sampling depths (surface, the
      maximum and minimum of the oxygen concentration, and near the seafloor) at 10
      oceanographic stations located in Bransfield Strait [northwest of the Antarctic
      Peninsula (AP)] and near the sea ice edge (north of the AP). Samples collected
      near the seafloor and at the oxygen minimum exhibited a higher diversity than
      those from the surface and oxygen maximum for both bacterial and archaeal
      communities. The main taxonomic groups identified below 100 m were
      Thaumarchaeota, Euryarchaeota and Proteobacteria (Gamma-, Delta-, Beta-, and
      Alphaproteobacteria), whereas in the mixed layer above 100 m Bacteroidetes and
      Proteobacteria (mainly Alpha- and Gammaproteobacteria) were found to be dominant.
      A combination of environmental factors seems to influence the microbial community
      composition. Our results help to understand how the dynamic seascape of the
      Southern Ocean shapes the microbial community composition and set a baseline for
      upcoming studies to evaluate the response of this ecosystem to future changes. 

PMID- 25566199
TI  - LDS1-produced oxylipins are negative regulators of growth, conidiation and
      fumonisin synthesis in the fungal maize pathogen Fusarium verticillioides.
AB  - Oxylipins are fatty acid-derived signaling compounds produced by all eukaryotes
      so far investigated; in mycotoxigenic fungi, they modulate toxin production and
      interactions with the host plants. Among the many enzymes responsible for
      oxylipin generation, Linoleate Diol Synthase 1 (LDS1) produces mainly 8
      hydroperoxyoctadecenoic acid and subsequently different di-hydroxyoctadecenoic
      acids. In this study, we inactivated a copy of the putative LDS1 ortholog (acc.
      N. FVEG_09294.3) of Fusarium verticillioides, with the aim to investigate its
      influence on the oxylipin profile of the fungus, on its development, secondary
      metabolism and virulence. LC-MS/MS oxylipin profiling carried out on the selected
      mutant strain revealed significant quali-quantitative differences for several
      oxylipins when compared to the WT strain. The Fvlds1-deleted mutant grew better,
      produced more conidia, synthesized more fumonisins and infected maize cobs faster
      than the WT strain. We hypothesize that oxylipins may act as regulators of gene
      expression in the toxigenic plant pathogen F. verticillioides, in turn causing
      notable changes in its phenotype. These changes could relate to the ability of
      oxylipins to re-shape the transcriptional profile of F. verticillioides by
      inducing chromatin modifications and exerting a direct control on the
      transcription of secondary metabolism in fungi. 

PMID- 25566201
TI  - H-NS is a repressor of major virulence gene loci in Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus, a leading cause of seafood-associated diarrhea and
      gastroenteritis, harbors three major virulence gene loci T3SS1, Vp-PAI
      (T3SS1+tdh2) and T6SS2. As showing in this study, the nucleoid-associated DNA
      binding regulator H-NS binds to multiple promoter-proximal regions in each of the
      above three loci to repress their transcription, and moreover H-NS inhibits the
      cytotoxicitiy, enterotoxicity, hemolytic activity, and mouse lethality of V.
      parahaemolyticus. H-NS appears to act as a major repressor of the virulence of
      this pathogen. Date presented here would promote us to gain a deeper
      understanding of H-NS-mediated silencing of horizontally acquired virulence loci
      in V. parahaemolyticus. 

PMID- 25566200
TI  - The many forms of a pleomorphic bacterial pathogen-the developmental network of
      Legionella pneumophila.
AB  - Legionella pneumophila is a natural intracellular bacterial parasite of free
      living freshwater protozoa and an accidental human pathogen that causes
      Legionnaires' disease. L. pneumophila differentiates, and does it in style.
      Recent experimental data on L. pneumophila's differentiation point at the
      existence of a complex network that involves many developmental forms. We intend
      readers to: (i) understand the biological relevance of L. pneumophila's forms
      found in freshwater and their potential to transmit Legionnaires' disease, and
      (ii) learn that the common depiction of L. pneumophila's differentiation as a
      biphasic developmental cycle that alternates between a replicative and a
      transmissive form is but an oversimplification of the actual process. Our
      specific objectives are to provide updates on the molecular factors that regulate
      L. pneumophila's differentiation (Section The Differentiation Process and Its
      Regulation), and describe the developmental network of L. pneumophila (Section
      Dissecting Lp's Developmental Network), which for clarity's sake we have
      dissected into five separate developmental cycles. Finally, since each
      developmental form seems to contribute differently to the human pathogenic
      process and the transmission of Legionnaires' disease, readers are presented with
      a challenge to develop novel methods to detect the various L. pneumophila forms
      present in water (Section Practical Implications), as a means to improve our
      assessment of risk and more effectively prevent legionellosis outbreaks. 

PMID- 25566202
TI  - Horizontal gene transfer and recombination in Streptococcus dysgalactiae subsp.
      equisimilis.
AB  - Streptococcus dysgalactiae subsp. equisimilis (SDSE) is a human pathogen that
      colonizes the skin or throat, and causes a range of diseases from relatively
      benign pharyngitis to potentially fatal invasive diseases. While not as virulent
      as the close relative Streptococcus pyogenes the two share a number of virulence
      factors and are known to coexist in a human host. Both pre- and post-genomic
      studies have revealed that horizontal gene transfer (HGT) and recombination
      occurs between these two organisms and plays a major role in shaping the
      population structure of SDSE. This review summarizes our current knowledge of HGT
      and recombination in the evolution of SDSE. 

PMID- 25566203
TI  - Comparisons of the composition and biogeographic distribution of the bacterial
      communities occupying South African thermal springs with those inhabiting deep
      subsurface fracture water.
AB  - South Africa has numerous thermal springs that represent topographically driven
      meteoric water migrating along major fracture zones. The temperature (40-70
      degrees C) and pH (8-9) of the thermal springs in the Limpopo Province are very
      similar to those of the low salinity fracture water encountered in the South
      African mines at depths ranging from 1.0 to 3.1 km. The major cation and anion
      composition of these thermal springs are very similar to that of the deep
      fracture water with the exception of the dissolved inorganic carbon and dissolved
      O2, both of which are typically higher in the springs than in the deep fracture
      water. The in situ biological relatedness of such thermal springs and the
      subsurface fracture fluids that feed them has not previously been evaluated. In
      this study, we evaluated the microbial diversity of six thermal spring and six
      subsurface sites in South Africa using high-throughput sequencing of 16S rRNA
      gene hypervariable regions. Proteobacteria were identified as the dominant phylum
      within both subsurface and thermal spring environments, but only one genera,
      Rheinheimera, was identified among all samples. Using Morisita similarity indices
      as a metric for pairwise comparisons between sites, we found that the communities
      of thermal springs are highly distinct from subsurface datasets. Although the
      Limpopo thermal springs do not appear to provide a new window for viewing
      subsurface bacterial communities, we report that the taxonomic compositions of
      the subsurface sites studied are more similar than previous results would
      indicate and provide evidence that the microbial communities sampled at depth are
      more correlated to subsurface conditions than geographical distance. 

PMID- 25566204
TI  - Soil bacterial community structure remains stable over a 5-year chronosequence of
      insect-induced tree mortality.
AB  - Extensive tree mortality from insect epidemics has raised concern over possible
      effects on soil biogeochemical processes. Yet despite the importance of microbes
      in nutrient cycling, how soil bacterial communities respond to insect-induced
      tree mortality is largely unknown. We examined soil bacterial community structure
      (via 16S rRNA gene pyrosequencing) and community assembly processes (via null
      deviation analysis) along a 5-year chronosequence (substituting space for time)
      of bark beetle-induced tree mortality in the southern Rocky Mountains, USA. We
      also measured microbial biomass and soil chemistry, and used in situ experiments
      to assess inorganic nitrogen mineralization rates. We found that bacterial
      community structure and assembly-which was strongly influenced by stochastic
      processes-were largely unaffected by tree mortality despite increased soil
      ammonium ([Formula: see text]) pools and reductions in soil nitrate ([Formula:
      see text]) pools and net nitrogen mineralization rates after tree mortality.
      Linear models suggested that microbial biomass and bacterial phylogenetic
      diversity are significantly correlated with nitrogen mineralization rates of this
      forested ecosystem. However, given the overall resistance of the bacterial
      community to disturbance from tree mortality, soil nitrogen processes likely
      remained relatively stable following tree mortality when considered at larger
      spatial and longer temporal scales-a supposition supported by the majority of
      available studies regarding biogeochemical effects of bark beetle infestations in
      this region. Our results suggest that soil bacterial community resistance to
      disturbance helps to explain the relatively weak effects of insect-induced tree
      mortality on soil N and C pools reported across the Rocky Mountains, USA. 

PMID- 25566205
TI  - HmsB enhances biofilm formation in Yersinia pestis.
AB  - The hmsHFRS operon is responsible for biosynthesis and translocation of biofilm
      matrix exopolysaccharide. Yersinia pestis expresses the two sole diguanylate
      cyclases HmsT and HmsD and the sole phosphodiesterase HmsP, which are specific
      for biosynthesis and degradation, respectively, of 3',5'-cyclic diguanosine
      monophosphate (c-di-GMP), a second messenger promoting exopolysaccharide
      production. In this work, the phenotypic assays indicates that Y. pestis sRNA
      HmsB enhances the production of c-di-GMP, exopolysaccharide, and biofilm. Further
      gene regulation experiments disclose that HmsB stimulates the expression of hmsB,
      hmsCDE, hmsT, and hmsHFRS but represses that of hmsP. HmsB most likely acts as a
      major activator of biofilm formation in Y. pestis. This is the first report of
      regulation of Yersinia biofilm formation by a sRNA. Data presented here will
      promote us to gain a deeper understanding of the complex regulatory circuits
      controlling Yersinia biofilm formation. 

PMID- 25566206
TI  - Evaluating controlled human malaria infection in Kenyan adults with varying
      degrees of prior exposure to Plasmodium falciparum using sporozoites administered
      by intramuscular injection.
AB  - BACKGROUND: Controlled human malaria infection (CHMI) studies are a vital tool to
      accelerate vaccine and drug development. As CHMI trials are performed in a
      controlled environment, they allow unprecedented, detailed evaluation of parasite
      growth dynamics (PGD) and immunological responses. However, CHMI studies have not
      been routinely performed in malaria-endemic countries or used to investigate
      mechanisms of naturally-acquired immunity (NAI) to Plasmodium falciparum.
      METHODS: We conducted an open-label, randomized CHMI pilot-study using aseptic,
      cryopreserved P. falciparum sporozoites (PfSPZ Challenge) to evaluate safety,
      infectivity and PGD in Kenyan adults with low to moderate prior exposure to P.
      falciparum (Pan African Clinical Trial Registry: PACTR20121100033272). RESULTS:
      All participants developed blood-stage infection confirmed by quantitative
      polymerase chain reaction (qPCR). However one volunteer (110) remained
      asymptomatic and blood-film negative until day 21 post-injection of PfSPZ
      Challenge. This volunteer had a reduced parasite multiplication rate (PMR) (1.3)
      in comparison to the other 27 volunteers (median 11.1). A significant correlation
      was seen between PMR and screening anti-schizont Enzyme Linked Immunosorbent
      Assays (ELISA) OD (p = 0.044, R = -0.384) but not when volunteer 110 was excluded
      from the analysis (p = 0.112, R = -0.313). CONCLUSIONS: PfSPZ Challenge is safe
      and infectious in malaria-endemic populations and could be used to assess the
      efficacy of malaria vaccines and drugs in African populations. Whilst our
      findings are limited by sample size, our pilot study has demonstrated for the
      first time that NAI may impact on PMR post-CHMI in a detectable fashion, an
      important finding that should be evaluated in further CHMI studies.

PMID- 25566207
TI  - F33: A-: B-, IncHI2/ST3, and IncI1/ST71 plasmids drive the dissemination of fosA3
      and bla CTX-M-55/-14/-65 in Escherichia coli from chickens in China.
AB  - The purpose of this study was to examine the occurrence of fosfomycin-resistant
      Escherichia coli from chickens and to characterize the plasmids carrying fosA3. A
      total of 661 E. coli isolates of chicken origin collected from 2009 to 2011 were
      screened for plasmid-mediated fosfomycin resistance determinants by PCR. Plasmids
      were characterized using PCR-based replicon typing, plasmid multilocus sequence
      typing, and restriction fragment length polymorphisms. Associated addiction
      systems and resistance genes were identified by PCR. PCR-mapping was used for
      analysis of the genetic context of fosA3. Fosfomycin resistance was detected in
      58 isolates that also carried the fosA3 gene. Fifty-seven, 17, and 52 FosA3
      producers also harbored bla CTX-M, rmtB, and floR genes, respectively. Most of
      the 58 fosA3-carrying isolates were clonally unrelated, and all fosA3 genes were
      located on plasmids belonged to F33:A-:B- (n = 18), IncN-F33:A-:B- (n = 7),
      IncHI2/ST3 (n = 10), IncI1/ST71 (n = 3), IncI1/ST108 (n = 3), and others. The
      genetic structures, IS26-ISEcp1-bla CTX-M-55-orf477-bla TEM-1-IS26-fosA3-1758bp
      IS26 and ISEcp1-bla CTX-M-65-IS903-iroN-IS26-fosA3-536bp-IS26 were located on
      highly similar F33:A-:B- plasmids. In addition, bla CTX-M-14-fosA3-IS26 was
      frequently present on similar IncHI2/ST3 plasmids. IncFII plasmids had a
      significantly higher frequency of addiction systems (mean 3.5) than other
      plasmids. Our results showed a surprisingly high prevalence of fosA3 gene in E.
      coli isolates recovered from chicken in China. The spread of fosA3 can be
      attributed to horizontal dissemination of several epidemic plasmids, especially
      F33:A-:B- plasmids. Since coselection by other antimicrobials is the major
      driving force for the diffusion of the fosA3 gene, a strict antibiotic use policy
      is urgently needed in China. 

PMID- 25566208
TI  - Transcriptomic analysis of Staphylococcus xylosus in the presence of nitrate and
      nitrite in meat reveals its response to nitrosative stress.
AB  - Staphylococcus xylosus is one of the major starter cultures used for meat
      fermentation because of its crucial role in the reduction of nitrate to nitrite
      which contributes to color and flavor development. Despite longstanding use of
      these additives, their impact on the physiology of S. xylosus has not yet been
      explored. We present the first in situ global gene expression profile of S.
      xylosus in meat supplemented with nitrate and nitrite at the levels used in the
      meat industry. More than 600 genes of S. xylosus were differentially expressed at
      24 or 72 h of incubation. They represent more than 20% of the total genes and let
      us to suppose that addition of nitrate and nitrite to meat leads to a global
      change in gene expression. This profile revealed that S. xylosus is subject to
      nitrosative stress caused by reactive nitrogen species (RNS) generated from
      nitrate and nitrite. To overcome this stress, S. xylosus has developed several
      oxidative stress resistance mechanisms, such as modulation of the expression of
      several genes involved in iron homeostasis and in antioxidant defense. Most of
      which belong to the Fur and PerR regulons, respectively. S. xylosus has also
      counteracted this stress by developing DNA and protein repair. Furthermore, it
      has adapted its metabolic response-carbon and nitrogen metabolism, energy
      production and cell wall biogenesis-to the alterations produced by nitrosative
      stress. 

PMID- 25566210
TI  - Spring thaw ionic pulses boost nutrient availability and microbial growth in
      entombed Antarctic Dry Valley cryoconite holes.
AB  - The seasonal melting of ice entombed cryoconite holes on McMurdo Dry Valley
      glaciers provides oases for life in the harsh environmental conditions of the
      polar desert where surface air temperatures only occasionally exceed 0 degrees C
      during the Austral summer. Here we follow temporal changes in cryoconite hole
      biogeochemistry on Canada Glacier from fully frozen conditions through the
      initial stages of spring thaw toward fully melted holes. The cryoconite holes had
      a mean isolation age from the glacial drainage system of 3.4 years, with an
      increasing mass of aqueous nutrients (dissolved organic carbon, total nitrogen,
      total phosphorus) with longer isolation age. During the initial melt there was a
      mean nine times enrichment in dissolved chloride relative to mean concentrations
      of the initial frozen holes indicative of an ionic pulse, with similar mean nine
      times enrichments in nitrite, ammonium, and dissolved organic matter. Nitrate was
      enriched twelve times and dissolved organic nitrogen six times, suggesting net
      nitrification, while lower enrichments for dissolved organic phosphorus and
      phosphate were consistent with net microbial phosphorus uptake. Rates of
      bacterial production were significantly elevated during the ionic pulse, likely
      due to the increased nutrient availability. There was no concomitant increase in
      photosynthesis rates, with a net depletion of dissolved inorganic carbon
      suggesting inorganic carbon limitation. Potential nitrogen fixation was detected
      in fully melted holes where it could be an important source of nitrogen to
      support microbial growth, but not during the ionic pulse where nitrogen
      availability was higher. This study demonstrates that ionic pulses significantly
      alter the timing and magnitude of microbial activity within entombed cryoconite
      holes, and adds credence to hypotheses that ionic enrichments during freeze-thaw
      can elevate rates of microbial growth and activity in other icy habitats, such as
      ice veins and subglacial regelation zones. 

PMID- 25566209
TI  - Biofilm growth mode promotes maximum carrying capacity and community stability
      during product inhibition syntrophy.
AB  - Sulfate-reducing bacteria (SRB) can interact syntrophically with other community
      members in the absence of sulfate, and interactions with hydrogen-consuming
      methanogens are beneficial when these archaea consume potentially inhibitory H2
      produced by the SRB. A dual continuous culture approach was used to characterize
      population structure within a syntrophic biofilm formed by the SRB Desulfovibrio
      vulgaris Hildenborough and the methanogenic archaeum Methanococcus maripaludis.
      Under the tested conditions, monocultures of D. vulgaris formed thin, stable
      biofilms, but monoculture M. maripaludis did not. Microscopy of intact syntrophic
      biofilm confirmed that D. vulgaris formed a scaffold for the biofilm, while
      intermediate and steady-state images revealed that M. maripaludis joined the
      biofilm later, likely in response to H2 produced by the SRB. Close interactions
      in structured biofilm allowed efficient transfer of H2 to M. maripaludis, and H2
      was only detected in cocultures with a mutant SRB that was deficient in biofilm
      formation (DeltapilA). M. maripaludis produced more carbohydrate (uronic acid,
      hexose, and pentose) as a monoculture compared to total coculture biofilm, and
      this suggested an altered carbon flux during syntrophy. The syntrophic biofilm
      was structured into ridges (~300 * 50 MUm) and models predicted lactate
      limitation at ~50 MUm biofilm depth. The biofilm had structure that likely
      facilitated mass transfer of H2 and lactate, yet maximized biomass with a more
      even population composition (number of each organism) when compared to the bulk
      phase community. Total biomass protein was equivalent in lactate-limited and
      lactate-excess conditions when a biofilm was present, but in the absence of
      biofilm, total biomass protein was significantly reduced. The results suggest
      that multispecies biofilms create an environment conducive to resource sharing,
      resulting in increased biomass retention, or carrying capacity, for cooperative
      populations. 

PMID- 25566211
TI  - Pyrococcus furiosus flagella: biochemical and transcriptional analyses identify
      the newly detected flaB0 gene to encode the major flagellin.
AB  - We have described previously that the flagella of the Euryarchaeon Pyrococcus
      furiosus are multifunctional cell appendages used for swimming, adhesion to
      surfaces and formation of cell-cell connections. Here, we characterize these
      organelles with respect to their biochemistry and transcription. Flagella were
      purified by shearing from cells followed by CsCl-gradient centrifugation and were
      found to consist mainly of a ca. 30 kDa glycoprotein. Polymerization studies of
      denatured flagella resulted in an ATP-independent formation of flagella-like
      filaments. The N-terminal sequence of the main flagellin was determined by Edman
      degradation, but none of the genes in the complete genome code for a protein with
      that N-terminus. Therefore, we resequenced the respective region of the genome,
      thereby discovering that the published genome sequence is not correct. A total of
      771 bp are missing in the data base, resulting in the correction of the
      previously unusual N-terminal sequence of flagellin FlaB1 and in the
      identification of a third flagellin. To keep in line with the earlier
      nomenclature we call this flaB0. Very interestingly, the previously not
      identified flaB0 codes for the major flagellin. Transcriptional analyses of the
      revised flagellar operon identified various different cotranscripts encoding only
      a single protein in case of FlaB0 and FlaJ or up to five proteins (FlaB0-FlaD).
      Analysing the RNA of cells from different growth phases, we found that the length
      and number of detected cotranscript increased over time suggesting that the
      flagellar operon is transcribed mostly in late exponential and stationary growth
      phase. 

PMID- 25566212
TI  - Analysis of biosurfactants from industrially viable Pseudomonas strain isolated
      from crude oil suggests how rhamnolipids congeners affect emulsification property
      and antimicrobial activity.
AB  - Rhamnolipid biosurfactants produced mainly by Pseudomonas sp. had been reported
      to possess a wide range of potential industrial application. These biosurfactants
      are produced as monorhamnolipid (MRL) and di-rhamnolipid (DRL) congeners. The
      present study deals with rhamnolipid biosurfactants produced by three bacterial
      isolates from crude oil. Biosurfactants produced by one of the strains (named as
      IMP67) was found to be very efficacious based on its critical micelle
      concentration value and hydrocarbon emulsification property. Strikingly,
      antimicrobial, and anti-biofilm potential of this biosurfactant were higher than
      biosurfactants produced by other two strains. Thin layer chromatography analysis
      and rhamnose quantification showed that the rhamnolipids of IMP67 had more MRL
      congeners than biosurfactants of the other two strains. Emulsification and
      antimicrobial actions were affected by manual change of MRL and DRL congener
      proportions. Increase of MRL proportion enhanced emulsification index and
      antimicrobial property to Gram negative bacteria. This result indicated that the
      ratio of MRL and DRL affected the emulsification potentials of rhamnolipids, and
      suggested that high emulsification potentials might enhance rhamnolipids to
      penetrate the cell wall of Gram negative bacteria. In line with this finding,
      rhamnolipids of IMP67 also reduced the MIC of some antibiotics against bacteria,
      suggesting their synergistic role with the antibiotics. 

PMID- 25566213
TI  - Cost effective technologies and renewable substrates for biosurfactants'
      production.
AB  - Diverse types of microbial surface active amphiphilic molecules are produced by a
      range of microbial communities. The extraordinary properties of
      biosurfactant/bioemulsifier (BS/BE) as surface active products allows them to
      have key roles in various field of applications such as bioremediation,
      biodegradation, enhanced oil recovery, pharmaceutics, food processing among many
      others. This leads to a vast number of potential applications of these BS/BE in
      different industrial sectors. Despite the huge number of reports and patents
      describing BS and BE applications and advantages, commercialization of these
      compounds remain difficult, costly and to a large extent irregular. This is
      mainly due to the usage of chemically synthesized media for growing producing
      microorganism and in turn the production of preferred quality products. It is
      important to note that although a number of developments have taken place in the
      field of BS industries, large scale production remains economically challenging
      for many types of these products. This is mainly due to the huge monetary
      difference between the investment and achievable productivity from the commercial
      point of view. This review discusses low cost, renewable raw substrates, and
      fermentation technology in BS/BE production processes and their role in reducing
      the production cost. 

PMID- 25566214
TI  - Metagenomic evidence for metabolism of trace atmospheric gases by high-elevation
      desert Actinobacteria.
AB  - Previous surveys of very dry Atacama Desert mineral soils have consistently
      revealed sparse communities of non-photosynthetic microbes. The functional nature
      of these microorganisms remains debatable given the harshness of the environment
      and low levels of biomass and diversity. The aim of this study was to gain an
      understanding of the phylogenetic community structure and metabolic potential of
      a low-diversity mineral soil metagenome that was collected from a high-elevation
      Atacama Desert volcano debris field. We pooled DNA extractions from over 15 g of
      volcanic material, and using whole genome shotgun sequencing, observed only 75-78
      total 16S rRNA gene OTUs3%. The phylogenetic structure of this community is
      significantly under dispersed, with actinobacterial lineages making up 97.9-98.6%
      of the 16S rRNA genes, suggesting a high degree of environmental selection. Due
      to this low diversity and uneven community composition, we assembled and analyzed
      the metabolic pathways of the most abundant genome, a Pseudonocardia sp. (56-72%
      of total 16S genes). Our assembly and binning efforts yielded almost 4.9 Mb of
      Pseudonocardia sp. contigs, which accounts for an estimated 99.3% of its non
      repetitive genomic content. This genome contains a limited array of carbohydrate
      catabolic pathways, but encodes for CO2 fixation via the Calvin cycle. The genome
      also encodes complete pathways for the catabolism of various trace gases (H2, CO
      and several organic C1 compounds) and the assimilation of ammonia and nitrate. We
      compared genomic content among related Pseudonocardia spp. and estimated rates of
      non-synonymous and synonymous nucleic acid substitutions between protein coding
      homologs. Collectively, these comparative analyses suggest that the community
      structure and various functional genes have undergone strong selection in the
      nutrient poor desert mineral soils and high-elevation atmospheric conditions. 

PMID- 25566216
TI  - Virus ecology and disturbances: impact of environmental disruption on the viruses
      of microorganisms.

PMID- 25566215
TI  - Oregano essential oil-pectin edible films as anti-quorum sensing and food
      antimicrobial agents.
AB  - Edible films can be used as carriers for antimicrobial compounds to assure food
      safety and quality; in addition, pathogenesis of food bacteria is related to a
      cell to cell communication mechanism called quorum sensing (QS). Oregano
      essential oil (OEO) has proved to be useful as food antimicrobial; however, its
      food applications can be compromised by the volatile character of its active
      constituents. Therefore, formulation of edible films containing OEO can be an
      alternative to improve its food usages. QS inhibitory activity of OEO and pectin
      OEO films was evaluated using Chromobacterium violaceum as bacterial model.
      Additionally, antibacterial activity was tested against Escherichia coli O157:H7,
      Salmonella Choleraesuis, Staphylococcus aureus, and Listeria monocytogenes. OEO
      was effective to inhibit bacterial growth at MIC of 0.24 mg/mL for all tested
      bacteria and MBC of 0.24, 0.24, 0.48, and 0.24 mg/mL against E. coli O157:H7, S.
      Choleraesuis, S. aureus, and L. monocytogenes, respectively. Pectin-films
      incorporated with 36.1 and 25.9 mg/mL of OEO showed inhibition diameters of 16.3
      and 15.2 mm for E. coli O157:H7; 18.1 and 24.2 mm for S. Choleraesuis; 20.8 and
      20.3 mm for S. aureus; 21.3 and 19.3 mm for L. monocytogenes, respectively.
      Pectin-OEO film (15.7 mg/mL) was effective against E. coli O157:H7 (9.3 mm), S.
      aureus (9.7 mm), and L. monocytogenes (9.2 mm), but not for S. Choleraesuis. All
      concentrations of OEO (0.0156, 0.0312, 0.0625 and 0.125 mg/mL) and pectin-OEO
      films (15.7, 25.9 and 36.1 mg/mL) showed a significant anti-QS activity expressed
      as inhibition of violacein production by C. violaceum. Additionally, the
      application of pectin-OEO films was effective reducing total coliforms, yeast,
      and molds of shrimp and cucumber slices stored at 4 degrees C during 15 d. These
      results demonstrated the potential of pectin films enriched with OEO as food
      related microorganisms and QS inhibitors. 

PMID- 25566217
TI  - YpfPhi: a filamentous phage acquired by Yersinia pestis.
AB  - Yersinia pestis, the plague bacillus, has an exceptional pathogenicity for
      humans. The plague bacillus emerged very recently (~3,000 years ago) from the
      enteropathogen Y. pseudotuberculosis. Early after its emergence, Y. pestis became
      infected by a filamentous phage named YpfPhi. During the microevolution of the
      plague bacillus, the phage remained in the various lineages as an unstable
      extrachromosomal element. However, in the sub branch that caused the third plague
      pandemic, YpfPhi integrated itself into the bacterial chromosome to become a
      stable prophage. The genome of this phage has the same genetic organization as
      that of other filamentous phages such as the Vibrio cholerae CTXPhi phage, and
      shares high sequence identity with the CUS-1 filamentous phage of a high
      virulence Escherichia coli K1 clone. In addition to genes involved in phage
      physiology, YpfPhi carries at each extremity of its genome two open reading
      frames with no predicted functions. This filamentous phage confers some selective
      properties to Y. pestis during the infectious process, which may explain why it
      was conserved duringY. pestis microevolution, despite its instability as an
      extrachromosomal element in most branches. 

PMID- 25566218
TI  - High temporal and spatial diversity in marine RNA viruses implies that they have
      an important role in mortality and structuring plankton communities.
AB  - Viruses in the order Picornavirales infect eukaryotes, and are widely distributed
      in coastal waters. Amplicon deep-sequencing of the RNA dependent RNA polymerase
      (RdRp) revealed diverse and highly uneven communities of picorna-like viruses in
      the coastal waters of British Columbia (BC), Canada. Almost 300 000 pyrosequence
      reads revealed 145 operational taxonomic units (OTUs) based on 95% sequence
      similarity at the amino-acid level. Each sample had between 24 and 71 OTUs and
      there was little overlap among samples. Phylogenetic analysis revealed that some
      clades of OTUs were only found at one site; whereas, other clades included OTUs
      from all sites. Since most of these OTUs are likely from viruses that infect
      eukaryotic phytoplankton, and viral isolates infecting phytoplankton are strain
      specific; each OTU probably arose from the lysis of a specific phytoplankton
      taxon. Moreover, the patchiness in OTU distribution, and the high turnover of
      viruses in the mixed layer, implies continuous infection and lysis by RNA viruses
      of a diverse array of eukaryotic phytoplankton taxa. Hence, these viruses are
      likely important elements structuring the phytoplankton community, and play a
      significant role in nutrient cycling and energy transfer. 

PMID- 25566221
TI  - Why the development of effective typhoid control measures requires the use of
      human challenge studies.

PMID- 25566220
TI  - Flipping the switch: tools for detecting small molecule inhibitors of
      staphylococcal virulence.
AB  - Through the expression of the accessory gene regulator quorum sensing cascade,
      Staphylococcus aureus is able to produce an extensive array of enzymes,
      hemolysins and immunomodulators essential to its ability to spread through the
      host tissues and cause disease. Many have argued for the discovery and
      development of quorum sensing inhibitors (QSIs) to augment existing antibiotics
      as adjuvant therapies. Here, we discuss the state-of-the-art tools that can be
      used to conduct screens for the identification of such QSIs. Examples include
      fluorescent reporters, MS-detection of autoinducing peptide production, agar
      plate methods for detection of hemolysins and lipase, High performance liquid
      chromatography-detection of hemolysins from supernatants, and cell-toxicity
      assays for detecting damage (or relief thereof) against human keratinocyte cells.
      In addition to providing a description of these various approaches, we also
      discuss their amenability to low-, medium-, and high-throughput screening efforts
      for the identification of novel QSIs. 

PMID- 25566219
TI  - Vibrio parahaemolyticus: a review on the pathogenesis, prevalence, and advance
      molecular identification techniques.
AB  - Vibrio parahaemolyticus is a Gram-negative halophilic bacterium that is found in
      estuarine, marine and coastal environments. V. parahaemolyticus is the leading
      causal agent of human acute gastroenteritis following the consumption of raw,
      undercooked, or mishandled marine products. In rare cases, V. parahaemolyticus
      causes wound infection, ear infection or septicaemia in individuals with pre
      existing medical conditions. V. parahaemolyticus has two hemolysins virulence
      factors that are thermostable direct hemolysin (tdh)-a pore-forming protein that
      contributes to the invasiveness of the bacterium in humans, and TDH-related
      hemolysin (trh), which plays a similar role as tdh in the disease pathogenesis.
      In addition, the bacterium is also encodes for adhesions and type III secretion
      systems (T3SS1 and T3SS2) to ensure its survival in the environment. This review
      aims at discussing the V. parahaemolyticus growth and characteristics,
      pathogenesis, prevalence and advances in molecular identification techniques. 

PMID- 25566223
TI  - Biodegradation of plastics in soil and effects on nitrification activity. A
      laboratory approach.
AB  - The progressive application of new biodegradable plastics in agriculture calls
      for improved testing approaches to assure their environmental safety. Full
      biodegradation (>=90%) prevents accumulation in soil, which is the first tier of
      testing. The application of specific ecotoxicity tests is the second tier of
      testing needed to show safety for the soil ecosystem. Soil microbial
      nitrification is widely used as a bioindicator for evaluating the impact of
      chemicals on soil but it is not applied for evaluating the impact of
      biodegradable plastics. In this work the International Standard test for
      biodegradation of plastics in soil (ISO 17556, 2012) was applied both to measure
      biodegradation and to prepare soil samples needed for a subsequent nitrification
      test based on another International Standard (ISO 14238, 2012). The plastic mulch
      film tested in this work showed full biodegradability and no inhibition of the
      nitrification potential of the soil in comparison with the controls. The
      laboratory approach suggested in this Technology Report enables (i) to follow the
      course of biodegradation, (ii) a strict control of variables and environmental
      conditions, (iii) the application of very high concentrations of test material
      (to maximize the possible effects). This testing approach could be taken into
      consideration in improved testing schemes aimed at defining the biodegradability
      of plastics in soil. 

PMID- 25566222
TI  - Chaophilic or chaotolerant fungi: a new category of extremophiles?
AB  - It is well known that few halophilic bacteria and archaea as well as certain
      fungi can grow at the highest concentrations of NaCl. However, data about
      possible life at extremely high concentrations of various others kosmotropic
      (stabilizing; like NaCl, KCl, and MgSO4) and chaotropic (destabilizing) salts
      (NaBr, MgCl2, and CaCl2) are scarce for prokaryotes and almost absent for the
      eukaryotic domain including fungi. Fungi from diverse (extreme) environments were
      tested for their ability to grow at the highest concentrations of kosmotropic and
      chaotropic salts ever recorded to support life. The majority of fungi showed
      preference for relatively high concentrations of kosmotropes. However, our study
      revealed the outstanding tolerance of several fungi to high concentrations of
      MgCl2 (up to 2.1 M) or CaCl2 (up to 2.0 M) without compensating kosmotropic
      salts. Few species, for instance Hortaea werneckii, Eurotium amstelodami,
      Eurotium chevalieri and Wallemia ichthyophaga, are able to thrive in media with
      the highest salinities of all salts (except for CaCl2 in the case of W.
      ichthyophaga). The upper concentration of MgCl2 to support fungal life in the
      absence of kosmotropes (2.1 M) is much higher than previously determined to be
      the upper limit for microbial growth (1.26 M). No fungal representatives showed
      exclusive preference for only chaotropic salts (being obligate chaophiles).
      Nevertheless, our study expands the knowledge of possible active life by a
      diverse set of fungi in biologically detrimental chaotropic environments. 

PMID- 25566224
TI  - Oil degradation and biosurfactant production by the deep sea bacterium Dietzia
      maris As-13-3.
AB  - Recent investigations of extreme environments have revealed numerous bioactive
      natural products. However, biosurfactant-producing strains from deep sea extreme
      environment are largely unknown. Here, we show that Dietzia maris As-13-3
      isolated from deep sea hydrothermal field could produce di-rhamnolipid as
      biosurfactant. The critical micelle concentration (CMC) of the purified di
      rhamnolipid was determined to be 120 mgL(-1), and it lowered the surface tension
      of water from 74 +/- 0.2 to 38 +/- 0.2 mN m(-1). Further, the alkane metabolic
      pathway-related genes and di-rhamnolipid biosynthesis-related genes were also
      analyzed by the sequencing genome of D. maris As-13-3 and quantitative real-time
      PCR (Q-PCR), respectively. Q-PCR analysis showed that all these genes were
      induced by n-Tetradecane, n-Hexadecane, and pristane. To the best of our
      knowledge, this is first report about the complete pathway of the di-rhamnolipid
      synthesis process in the genus Dietzia. Thus, our study provided the insights
      into Dietzia in respects of oil degradation and biosurfactant production, and
      will help to evaluate the potential of Dietzia in marine oil removal. 

PMID- 25566225
TI  - The dam replacing gene product enhances Neisseria gonorrhoeae FA1090 viability
      and biofilm formation.
AB  - Many Neisseriaceae do not exhibit Dam methyltransferase activity and, instead of
      the dam gene, possess drg (dam replacing gene) inserted in the leuS/dam locus.
      The drg locus in Neisseria gonorrhoeae FA1090 has a lower GC-pairs content
      (40.5%) compared to the whole genome of N. gonorrhoeae FA1090 (52%). The
      gonococcal drg gene encodes a DNA endonuclease Drg, with GmeATC specificity.
      Disruption of drg or insertion of the dam gene in gonococcal genome changes the
      level of expression of genes as shown by transcriptome analysis. For the drg
      deficient N. gonorrhoeae mutant, a total of 195 (8.94% of the total gene pool)
      genes exhibited an altered expression compared to the wt strain by at least 1.5
      fold. In dam-expressing N. gonorrhoeae mutant, the expression of 240 genes (11%
      of total genes) was deregulated. Most of these deregulated genes were involved in
      translation, DNA repair, membrane biogenesis and energy production as shown by
      cluster of orthologous group analysis. In vivo, the inactivation of drg gene
      causes the decrease of the number of live neisserial cells and long lag phase of
      growth. The insertion of dam gene instead of drg locus restores cell viability.
      We have also shown that presence of the drg gene product is important for N.
      gonorrhoeae FA1090 in adhesion, including human epithelial cells, and biofilm
      formation. Biofilm produced by drg-deficient strain is formed by more dispersed
      cells, compared to this one formed by parental strain as shown by scanning
      electron and confocal microscopy. Also adherence assays show a significantly
      smaller biomass of formed biofilm (OD570 = 0.242 +/- 0.038) for drg-deficient
      strain, compared to wild-type strain (OD570 = 0.378 +/- 0.057). Dam-expressing
      gonococcal cells produce slightly weaker biofilm with cells embedded in an
      extracellular matrix. This strain has also a five times reduced ability for
      adhesion to human epithelial cells. In this context, the presence of Drg is more
      advantageous for N. gonorrhoeae biology than Dam presence. 

PMID- 25566226
TI  - Assembly of viral genomes from metagenomes.
AB  - Viral infections remain a serious global health issue. Metagenomic approaches are
      increasingly used in the detection of novel viral pathogens but also to generate
      complete genomes of uncultivated viruses. In silico identification of complete
      viral genomes from sequence data would allow rapid phylogenetic characterization
      of these new viruses. Often, however, complete viral genomes are not recovered,
      but rather several distinct contigs derived from a single entity are, some of
      which have no sequence homology to any known proteins. De novo assembly of single
      viruses from a metagenome is challenging, not only because of the lack of a
      reference genome, but also because of intrapopulation variation and uneven or
      insufficient coverage. Here we explored different assembly algorithms, remote
      homology searches, genome-specific sequence motifs, k-mer frequency ranking, and
      coverage profile binning to detect and obtain viral target genomes from
      metagenomes. All methods were tested on 454-generated sequencing datasets
      containing three recently described RNA viruses with a relatively large genome
      which were divergent to previously known viruses from the viral families
      Rhabdoviridae and Coronaviridae. Depending on specific characteristics of the
      target virus and the metagenomic community, different assembly and in silico gap
      closure strategies were successful in obtaining near complete viral genomes. 

PMID- 25566227
TI  - Recent advances in genome mining of secondary metabolites in Aspergillus terreus.
AB  - Filamentous fungi are rich resources of secondary metabolites (SMs) with a
      variety of interesting biological activities. Recent advances in genome
      sequencing and techniques in genetic manipulation have enabled researchers to
      study the biosynthetic genes of these SMs. Aspergillus terreus is the well-known
      producer of lovastatin, a cholesterol-lowering drug. This fungus also produces
      other SMs, including acetylaranotin, butyrolactones, and territram, with
      interesting bioactivities. This review will cover recent progress in genome
      mining of SMs identified in this fungus. The identification and characterization
      of the gene cluster for these SMs, as well as the proposed biosynthetic pathways,
      will be discussed in depth. 

PMID- 25566228
TI  - Enhancing microbial metabolite and enzyme production: current strategies and
      challenges.

PMID- 25566230
TI  - Microbial carbon mineralization in tropical lowland and montane forest soils of
      Peru.
AB  - Climate change is affecting the amount and complexity of plant inputs to tropical
      forest soils. This is likely to influence the carbon (C) balance of these
      ecosystems by altering decomposition processes e.g., "positive priming effects"
      that accelerate soil organic matter mineralization. However, the mechanisms
      determining the magnitude of priming effects are poorly understood. We
      investigated potential mechanisms by adding (13)C labeled substrates, as
      surrogates of plant inputs, to soils from an elevation gradient of tropical
      lowland and montane forests. We hypothesized that priming effects would increase
      with elevation due to increasing microbial nitrogen limitation, and that
      microbial community composition would strongly influence the magnitude of priming
      effects. Quantifying the sources of respired C (substrate or soil organic matter)
      in response to substrate addition revealed no consistent patterns in priming
      effects with elevation. Instead we found that substrate quality (complexity and
      nitrogen content) was the dominant factor controlling priming effects. For
      example a nitrogenous substrate induced a large increase in soil organic matter
      mineralization whilst a complex C substrate caused negligible change. Differences
      in the functional capacity of specific microbial groups, rather than microbial
      community composition per se, were responsible for these substrate-driven
      differences in priming effects. Our findings suggest that the microbial pathways
      by which plant inputs and soil organic matter are mineralized are determined
      primarily by the quality of plant inputs and the functional capacity of microbial
      taxa, rather than the abiotic properties of the soil. Changes in the complexity
      and stoichiometry of plant inputs to soil in response to climate change may
      therefore be important in regulating soil C dynamics in tropical forest soils. 

PMID- 25566231
TI  - Tolerance response of multidrug-resistant Salmonella enterica strains to
      habituation to Origanum vulgare L. essential oil.
AB  - Multidrug-resistant Salmonella enterica isolates from human outbreaks or from
      poultry origin were investigated for their ability to develop direct-tolerance or
      cross-tolerance to sodium chloride, potassium chloride, lactic acid, acetic acid,
      and ciprofloxacin after habituation in subinhibitory amounts ( of the minimum
      inhibitory concentration - (MIC) and of the minimum inhibitory concentration -
      MIC) of Origanum vulgare L. essential oil (OVEO) at different time intervals. The
      habituation of S. enterica to OVEO did not induce direct-tolerance or cross
      tolerance in the tested strains, as assessed by the modulation of MIC values.
      However, cells habituated to OVEO maintained or increased susceptibility to the
      tested antimicrobials agents, with up to fourfold double dilution decrease from
      previously determined MIC values. This study reports for the first time the non
      inductive effect of OVEO on the acquisition of direct-tolerance or cross
      tolerance in multidrug-resistant S. enterica strains to antimicrobial agents that
      are largely used in food preservation, as well as to CIP, the therapeutic drug of
      salmonellosis. 

PMID- 25566229
TI  - The multifaceted roles of metabolic enzymes in the Paracoccidioides species
      complex.
AB  - Paracoccidioides species are dimorphic fungi and are the etiologic agents of
      paracoccidioidomycosis, which is a serious disease that involves multiple organs.
      The many tissues colonized by this fungus suggest a variety of surface molecules
      involved in adhesion. A surprising finding is that most enzymes in the glycolytic
      pathway, tricarboxylic acid (TCA) cycle and glyoxylate cycle in Paracoccidioides
      spp. have adhesive properties that aid in interacting with the host extracellular
      matrix and thus act as 'moonlighting' proteins. Moonlighting proteins have
      multiple functions, which adds a dimension to cellular complexity and benefit
      cells in several ways. This phenomenon occurs in both eukaryotes and prokaryotes.
      For example, moonlighting proteins from the glycolytic pathway or TCA cycle can
      play a role in bacterial pathogenesis by either acting as proteins secreted in a
      conventional pathway and/or as cell surface components that facilitate adhesion
      or adherence. This review outlines the multifunctionality exhibited by many
      Paracoccidioides spp. enzymes, including aconitase, aldolase, glyceraldehyde-3
      phosphate dehydrogenase, isocitrate lyase, malate synthase, triose phosphate
      isomerase, fumarase, and enolase. We discuss the roles that moonlighting
      activities play in the virulence characteristics of this fungus and several other
      human pathogens during their interactions with the host. 

PMID- 25566232
TI  - Antimicrobial resistance characteristics and fitness of Gram-negative fecal
      bacteria from volunteers treated with minocycline or amoxicillin.
AB  - A yearlong study was performed to examine the effect of antibiotic administration
      on the bacterial gut flora. Gram-negative facultative anaerobic bacteria were
      recovered from the feces of healthy adult volunteers administered amoxicillin,
      minocycline or placebo, and changes determined in antimicrobial resistance (AMR)
      gene carriage. Seventy percent of the 1039 facultative anaerobic isolates
      recovered were identified by MALDI-TOF as Escherichia coli. A microarray used to
      determine virulence and resistance gene carriage demonstrated that AMR genes were
      widespread in all administration groups, with the most common resistance genes
      being bla TEM, dfr, strB, tet(A), and tet(B). Following amoxicillin
      administration, an increase in the proportion of amoxicillin resistant E. coli
      and a three-fold increase in the levels of bla TEM gene carriage was observed, an
      effect not observed in the other two treatment groups. Detection of virulence
      genes, including stx1A, indicated not all E. coli were innocuous commensals.
      Approximately 150 E. coli collected from 6 participants were selected for pulse
      field gel electrophoresis (PFGE), and a subset used for characterisation of
      plasmids and Phenotypic Microarrays (PM). PFGE indicated some E. coli clones had
      persisted in volunteers for up to 1 year, while others were transient. Although
      there were no unique characteristics associated with plasmids from persistent or
      transient isolates, PM assays showed transient isolates had greater adaptability
      to a range of antiseptic biocides and tetracycline; characteristics which were
      lost in some, but not all persistent isolates. This study indicates healthy
      individuals carry bacteria harboring resistance to a variety of antibiotics and
      biocides in their intestinal tract. Antibiotic administration can have a
      temporary effect of selecting bacteria, showing co-resistance to multiple
      antibiotics, some of which can persist within the gut for up to 1 year. 

PMID- 25566234
TI  - Complexity of bacterial phosphorylation interaction network.

PMID- 25566233
TI  - Emerging methods to study bacteriophage infection at the single-cell level.
AB  - Bacteria and their viruses (phages) are abundant across diverse ecosystems and
      their interactions influence global biogeochemical cycles and incidence of
      disease. Problematically, both classical and metagenomic methods insufficiently
      assess the host specificity of phages and phage-host infection dynamics in
      nature. Here we review emerging methods to study phage-host interaction and
      infection dynamics with a focus on those that offer resolution at the single-cell
      level. These methods leverage ever-increasing sequence data to identify virus
      signals from single-cell amplified genome datasets or to produce primers/probes
      to target particular phage-bacteria pairs (digital PCR and phageFISH), even in
      complex communities. All three methods enable study of phage infection of
      uncultured bacteria from environmental samples, while the latter also
      discriminates between phage-host interaction outcomes (e.g., lytic, chronic,
      lysogenic) in model systems. Together these techniques enable quantitative,
      spatiotemporal studies of phage-bacteria interactions from environmental samples
      of any ecosystem, which will help elucidate and predict the ecological and
      evolutionary impacts of specific phage-host pairings in nature. 

PMID- 25566235
TI  - Vaccination against Q fever for biodefense and public health indications.
AB  - Coxiella burnetii is the etiological agent of Q fever, a disease that is often
      spread to humans via inhalational exposure to the bacteria from contaminated
      agricultural sources. Outbreaks have been observed all over the world with larger
      foci generating interest in vaccination programs, most notably in Australia and
      the Netherlands. Importantly, exposure rates among military personnel deployed to
      the Middle East can be relatively high as measured by seroconversion to C.
      burnetii-specific antibodies. Q fever has been of interest to the biodefense
      community over the years due to its low infectious dose and environmental
      stability. Recent advances in cell-free growth and genetics of C. burnetii also
      make this organism easier to culture and manipulate. While there is a vaccine
      that is licensed for use in Australia, the combination of biodefense- and public
      health-related issues associated with Q fever warrant the development of a safer
      and more effective vaccine against this disease. 

PMID- 25566236
TI  - The fundamental role of endothelial cells in hantavirus pathogenesis.
AB  - Hantavirus, a genus of rodent- and insectivore-borne viruses in the family
      Bunyaviridae, is a group of emerging zoonotic pathogens. Hantaviruses cause
      hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome in
      man, often with severe consequences. Vascular leakage is evident in severe
      hantavirus infections, and increased permeability contributes to the
      pathogenesis. This review summarizes the current knowledge on hantavirus
      interactions with hematopoietic and endothelial cells, and their effects on the
      increased vascular permeability. 

PMID- 25566237
TI  - Molecular signature of Epstein Barr virus-positive Burkitt lymphoma and post
      transplant lymphoproliferative disorder suggest different roles for Epstein Barr
      virus.
AB  - Epstein Barr virus (EBV) infection is commonly associated with human cancer and,
      in particular, with lymphoid malignancies. Although the precise role of the virus
      in the pathogenesis of different lymphomas is largely unknown, it is well
      recognized that the expression of viral latent proteins and miRNA can contribute
      to its pathogenetic role. In this study, we compared the gene and miRNA
      expression profile of two EBV-associated aggressive B non-Hodgkin lymphomas known
      to be characterized by differential expression of the viral latent proteins
      aiming to dissect the possible different contribution of such proteins and EBV
      encoded miRNAs. By applying extensive bioinformatic inferring and an experimental
      model, we found that EBV+ Burkitt lymphoma presented with significant over
      expression of EBV-encoded miRNAs that were likely to contribute to its global
      molecular profile. On the other hand, EBV+ post-transplant diffuse large B-cell
      lymphomas presented a significant enrichment in genes regulated by the viral
      latent proteins. Based on these different viral and cellular gene expression
      patterns, a clear distinction between EBV+ Burkitt lymphoma and post-transplant
      diffuse large B-cell lymphomas was made. In this regard, the different viral and
      cellular expression patterns seemed to depend on each other, at least partially,
      and the latency type most probably played a significant role in their regulation.
      In conclusion, our data indicate that EBV influence over B-cell malignant clones
      may act through different mechanisms of transcriptional regulation and suggest
      that potentially different pathogenetic mechanisms may depend upon the conditions
      of the interaction between EBV and the host that finally determine the latency
      pattern. 

PMID- 25566238
TI  - Novel assay to measure the plasmid mobilizing potential of mixed microbial
      communities.
AB  - Mobilizable plasmids lack necessary genes for complete conjugation and are
      therefore non-self-transmissible. Instead, they rely on the conjugation system of
      conjugal plasmids to be horizontally transferred to new recipients. While
      community permissiveness, the fraction of a mixed microbial community that can
      receive self-transmissible conjugal plasmids, has been studied, the intrinsic
      ability of a community to mobilize plasmids that lack conjugation systems is
      unexplored. Here, we present a novel framework and experimental method to
      estimate the mobilization potential of mixed communities. We compare the transfer
      frequency of a mobilizable plasmid to that of a mobilizing and conjugal plasmid
      measured for a model strain and for the assayed community. With Pseudomonas
      putida carrying the gfp-tagged mobilizable IncQ plasmid RSF1010 as donor strain,
      we conducted solid surface mating experiments with either a P. putida strain
      carrying the mobilizing IncP-1alpha plasmid RP4 or a model bacterial community
      that was extracted from the inner walls of a domestic shower conduit.
      Additionally, we estimated the permissiveness of the same community for RP4 using
      P. putida as donor strain. The permissiveness of the model community for RP4 [at
      1.16 * 10(-4) transconjugants per recipient (T/R)] was similar to that previously
      measured for soil microbial communities. RSF1010 was mobilized by the model
      community at a frequency of 1.16 * 10(-5) T/R, only one order of magnitude lower
      than its permissiveness to RP4. This mobilization frequency is unexpectedly high
      considering that (i) mobilization requires the presence of mobilizing conjugal
      plasmids within the permissive fraction of the recipients; (ii) in pure culture
      experiments with P. putida retromobilization of RSF1010 through RP4 only took
      place in approximately half of the donors receiving the conjugal plasmid in the
      first step. Further work is needed to establish how plasmid mobilization
      potential varies within and across microbial communities. This method has the
      potential to provide such insights; in addition it allows for the direct
      isolation of in situ mobilizing plasmids together with their endogenous hosts. 

PMID- 25566239
TI  - Association and dissociation of the GlnK-AmtB complex in response to cellular
      nitrogen status can occur in the absence of GlnK post-translational modification.
AB  - PII proteins are pivotal players in the control of nitrogen metabolism in
      bacteria and archaea, and are also found in the plastids of plants. PII proteins
      control the activities of a diverse range of enzymes, transcription factors and
      membrane transport proteins, and their regulatory effect is achieved by direct
      interaction with their target. Many, but by no means all, PII proteins are
      subject to post-translational modification of a residue within the T-loop of the
      protein. The protein's modification state is influenced by the cellular nitrogen
      status and in the past this has been considered to regulate PII activity by
      controlling interaction with target proteins. However, the fundamental ability of
      PII proteins to respond to the cellular nitrogen status has been shown to be
      dependent on binding of key effector molecules, ATP, ADP, and 2-oxoglutarate
      which brings into question the precise role of post-translational modification.
      In this study we have used the Escherichia coli PII protein GlnK to examine the
      influence of post-translational modification (uridylylation) on the interaction
      between GlnK and its cognate target the ammonia channel protein AmtB. We have
      compared the interaction with AmtB of wild-type GlnK and a variant protein,
      GlnKTyr51Ala, that cannot be uridylylated. This analysis was carried out both in
      vivo and in vitro and showed that association and dissociation of the GlnK-AmtB
      complex is not dependent on the uridylylation state of GlnK. However, our in vivo
      studies show that post-translational modification of GlnK does influence the
      dynamics of its interaction with AmtB. 

PMID- 25566240
TI  - Chemical strategies for the covalent modification of filamentous phage.
AB  - Historically filamentous bacteriophage have been known to be the workhorse of
      phage display due to their ability to link genotype to phenotype. More recently,
      the filamentous phage scaffold has proven to be powerful outside the realm of
      phage display technology in fields such as molecular imaging, cancer research and
      materials, and vaccine development. The ability of the virion to serve as a
      platform for a variety of applications heavily relies on the functionalization of
      the phage coat proteins with a wide variety of functionalities. Genetic
      modification of the coat proteins has been the most widely used strategy for
      functionalizing the virion; however, complementary chemical modification
      strategies can help to diversify the range of materials that can be developed.
      This review emphasizes the recent advances that have been made in the chemical
      modification of filamentous phage as well as some of the challenges that are
      involved in functionalizing the virion. 

PMID- 25566241
TI  - Transcription factors FabR and FadR regulate both aerobic and anaerobic pathways
      for unsaturated fatty acid biosynthesis in Shewanella oneidensis.
AB  - As genes for type II fatty acid synthesis are essential to the growth of
      Escherichia coli, its sole (anaerobic) pathway has significant potential as a
      target for novel antibacterial drug, and has been extensively studied. Despite
      this, we still know surprisingly little about fatty acid synthesis in bacteria
      because this anaerobic pathway in fact is not widely distributed. In this study,
      we show a novel model of unsaturated fatty acid (UFA) synthesis in Shewanella,
      emerging human pathogens in addition to well-known metal reducers. We identify
      both anaerobic and aerobic UFA biosynthesis pathways in the representative
      species, S. oneidensis. Uniquely, the bacterium also contains two regulators FabR
      and FadR, whose counterparts in other bacteria control the anaerobic pathway.
      However, we show that in S. oneidensis these two regulators are involved in
      regulation of both pathways, in either direct or indirect manner. Overall, our
      results indicate that the UFA biosynthesis and its regulation are far more
      complex than previously expected, and S. oneidensis serves as a good research
      model for further work. 

PMID- 25566242
TI  - The Subtleties and Contrasts of the LeuO Regulator in Salmonella Typhi:
      Implications in the Immune Response.
AB  - Salmonella are facultative intracellular pathogens. Salmonella infection occurs
      mainly by expression of two Salmonella pathogenicity Islands (SPI-1 and SPI-2).
      SPI-1 encodes transcriptional factors that participate in the expression of
      virulence factors encoded in the island. However, there are transcriptional
      factors encoded outside the island that also participate in the expression of SPI
      1-encoded genes. Upon infection, bacteria are capable of avoiding the host immune
      response with several strategies that involve several virulence factors under the
      control of transcriptional regulators. Interestingly, LeuO a transcriptional
      global regulator which is encoded outside of any SPI, is proposed to be part of a
      complex regulatory network that involves expression of several genes that help
      bacteria to survive stress conditions and, also, induces the expression of porins
      that have been shown to be immunogens and can thus be considered as antigenic
      candidates for acellular vaccines. Hence, the understanding of the LeuO regulon
      implies a role of bacterial genetic regulation in determining the host immune
      response. 

PMID- 25566243
TI  - Primary immune deficiencies - principles of care.
AB  - Primary immune deficiencies (PIDs) are a growing group of over 230 different
      disorders caused by ineffective, absent or an increasing number of gain of
      function mutations in immune components, mainly cells and proteins. Once
      recognized, these rare disorders are treatable and in some cases curable.
      Otherwise untreated PIDs are often chronic, serious, or even fatal. The diagnosis
      of PIDs can be difficult due to lack of awareness or facilities for diagnosis,
      and management of PIDs is complex. This document was prepared by a worldwide
      multi-disciplinary team of specialists; it aims to set out comprehensive
      principles of care for PIDs. These include the role of specialized centers, the
      importance of registries, the need for multinational research, the role of
      patient organizations, management and treatment options, the requirement for
      sustained access to all treatments including immunoglobulin therapies and
      hematopoietic stem cell transplantation, important considerations for developing
      countries and suggestions for implementation. A range of healthcare policies and
      services have to be put into place by government agencies and healthcare
      providers, to ensure that PID patients worldwide have access to appropriate and
      sustainable medical and support services. 

PMID- 25566246
TI  - Chromatin and transcriptional tango on the immune dance floor.

PMID- 25566247
TI  - Neutralization-Enhancing RF Antibodies for HIV Vaccines.

PMID- 25566248
TI  - Antibodies and protection against invasive salmonella disease.

PMID- 25566245
TI  - Plasticity of human CD4 T cell subsets.
AB  - Human beings are exposed to a variety of different pathogens, which induce
      tailored immune responses and consequently generate highly diverse populations of
      pathogen-specific T cells. CD4(+) T cells have a central role in adaptive
      immunity, since they provide essential help for both cytotoxic T cell- and
      antibody-mediated responses. In addition, CD4(+) regulatory T cells are required
      to maintain self-tolerance and to inhibit immune responses that could damage the
      host. Initially, two subsets of CD4(+) helper T cells were identified that
      secrete characteristic effector cytokines and mediate responses against different
      types of pathogens, i.e., IFN-gamma secreting Th1 cells that fight intracellular
      pathogens, and IL-4 producing Th2 cells that target extracellular parasites. It
      is now well established that this dichotomy is insufficient to describe the
      complexity of CD4(+) T cell differentiation, and in particular the human CD4
      compartment contains a myriad of T cell subsets with characteristic capacities to
      produce cytokines and to home to involved tissues. Moreover, it has become
      increasingly clear that these T cell subsets are not all terminally
      differentiated cells, but that the majority is plastic and that in particular
      central memory T cells can acquire different properties and functions in
      secondary immune responses. In addition, there is compelling evidence that helper
      T cells can acquire regulatory functions upon chronic stimulation in inflamed
      tissues. The plasticity of antigen-experienced human T cell subsets is highly
      relevant for translational medicine, since it opens new perspectives for immune
      modulatory therapies for chronic infections, autoimmune diseases, and cancer. 

PMID- 25566244
TI  - Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long
      debate in europe.
AB  - The consumption of immunoglobulins (Ig) is increasing due to better recognition
      of antibody deficiencies, an aging population, and new indications. This review
      aims to examine the various dosing regimens and research developments in the
      established and in some of the relevant off-label indications in Europe. The
      background to the current regulatory settings in Europe is provided as a backdrop
      for the latest developments in primary and secondary immunodeficiencies and in
      immunomodulatory indications. In these heterogeneous areas, clinical trials
      encompassing different routes of administration, varying intervals, and infusion
      rates are paving the way toward more individualized therapy regimens. In primary
      antibody deficiencies, adjustments in dosing and intervals will depend on the
      clinical presentation, effective IgG trough levels and IgG metabolism. Ideally,
      individual pharmacokinetic profiles in conjunction with the clinical phenotype
      could lead to highly tailored treatment. In practice, incremental dosage
      increases are necessary to titrate the optimal dose for more severely ill
      patients. Higher intravenous doses in these patients also have beneficial
      immunomodulatory effects beyond mere IgG replacement. Better understanding of the
      pharmacokinetics of Ig therapy is leading to a move away from simplistic "per kg"
      dosing. Defective antibody production is common in many secondary
      immunodeficiencies irrespective of whether the causative factor was lymphoid
      malignancies (established indications), certain autoimmune disorders,
      immunosuppressive agents, or biologics. This antibody failure, as shown by test
      immunization, may be amenable to treatment with replacement Ig therapy. In
      certain immunomodulatory settings [e.g., idiopathic thrombocytopenic purpura
      (ITP)], selection of patients for Ig therapy may be enhanced by relevant
      biomarkers in order to exclude non-responders and thus obtain higher response
      rates. In this review, the developments in dosing of therapeutic immunoglobulins
      have been limited to high and some medium priority indications such as ITP,
      Kawasaki' disease, Guillain-Barre syndrome, chronic inflammatory demyelinating
      polyradiculoneuropathy, myasthenia gravis, multifocal motor neuropathy, fetal
      alloimmune thrombocytopenia, fetal hemolytic anemia, and dermatological diseases.

PMID- 25566250
TI  - Persistent Immune Activation in CVID and the Role of IVIg in Its Suppression.
AB  - Common variable immunodeficiency (CVID) is one of the most common and clinically
      important primary immune deficiencies. CVID patients have poor humoral immunity,
      resulting in recurrent infections of the gastrointestinal and upper respiratory
      tracts, as well as increased incidence of some forms of cancers and autoimmune
      diseases. The treatment for CVID is IgG replacement, often given as intravenous
      immunoglobulins (IVIg). IVIg consists of monomeric IgG purified from pooled
      plasma from healthy donors and is used to treat an increasing number of
      conditions including autoimmune diseases. In the case of CVID, IVIg has mainly
      been seen as reconstitution therapy, providing patients with pathogen-specific
      antibodies. Recent evidence shows that IVIg has diverse effects on the immune
      system of CVID patients, and one important component is that IVIg alleviates the
      state of chronic immune activation. In this review, we will discuss causes and
      consequences of persistent immune activation in CVID, possible underlying
      mechanisms for how IVIg treatment reduces immune activation, and implications for
      our understanding of primary as well as acquired immune deficiencies. 

PMID- 25566251
TI  - Different Toll-Like Receptor Expression Patterns in Progression toward Cancer.

PMID- 25566252
TI  - Revisiting the identification and cDNA cloning of T cell-replacing
      factor/interleukin-5.
AB  - This is a perspective based on the paper "Cloning of complementary DNA encoding T
      cell-replacing factor and identity with B cell growth factor II," by Kinashi et
      al. (1). We have been interested in understanding the molecular basis of T-B cell
      cooperation for antibody formation. Although many investigators had described a
      number of different soluble factors that appeared to have biological relevance to
      T-B cell interactions, molecular basis of such active substances remained unknown
      for a long period of time. In this perspective, I will briefly summarize the
      history of the initial discovery of T cell-replacing factor/B cell growth factor
      II that appeared to be involved in B cell growth and differentiation, and outline
      the discovery and characterization of interleukin-5. Studies of interleukin-5
      have provided strong evidence that a single cytokine exerts a variety of
      activities on diverse target cells. 

PMID- 25566253
TI  - Tryptophan Feeding of the IDO1-AhR Axis in Host-Microbial Symbiosis.

PMID- 25566249
TI  - Clinical applications of gamma delta T cells with multivalent immunity.
AB  - gammadelta T cells hold promise for adoptive immunotherapy because of their
      reactivity to bacteria, viruses, and tumors. However, these cells represent a
      small fraction (1-5%) of the peripheral T-cell pool and require activation and
      propagation to achieve clinical benefit. Aminobisphosphonates specifically expand
      the Vgamma9Vdelta2 subset of gammadelta T cells and have been used in clinical
      trials of cancer where objective responses were detected. The Vgamma9Vdelta2 T
      cell receptor (TCR) heterodimer binds multiple ligands and results in a
      multivalent attack by a monoclonal T cell population. Alternatively, populations
      of gammadelta T cells with oligoclonal or polyclonal TCR repertoire could be
      infused for broad-range specificity. However, this goal has been restricted by a
      lack of applicable expansion protocols for non-Vgamma9Vdelta2 cells. Recent
      advances using immobilized antigens, agonistic monoclonal antibodies (mAbs),
      tumor-derived artificial antigen presenting cells (aAPC), or combinations of
      activating mAbs and aAPC have been successful in expanding gamma delta T cells
      with oligoclonal or polyclonal TCR repertoires. Immobilized major
      histocompatibility complex Class-I chain-related A was a stimulus for gammadelta
      T cells expressing TCRdelta1 isotypes, and plate-bound activating antibodies have
      expanded Vdelta1 and Vdelta2 cells ex vivo. Clinically sufficient quantities of
      TCRdelta1, TCRdelta2, and TCRdelta1(neg)TCRdelta2(neg) have been produced
      following co-culture on aAPC, and these subsets displayed differences in memory
      phenotype and reactivity to tumors in vitro and in vivo. Gamma delta T cells are
      also amenable to genetic modification as evidenced by introduction of alphabeta
      TCRs, chimeric antigen receptors, and drug-resistance genes. This represents a
      promising future for the clinical application of oligoclonal or polyclonal
      gammadelta T cells in autologous and allogeneic settings that builds on current
      trials testing the safety and efficacy of Vgamma9Vdelta2 T cells. 

PMID- 25566254
TI  - The role of Fatty Acid oxidation in the metabolic reprograming of activated t
      cells.
AB  - Activation represents a significant bioenergetic challenge for T-cells, which
      must undergo metabolic reprogramming to keep pace with increased energetic
      demands. This review focuses on the role of fatty acid metabolism, both in vitro
      and in vivo, following T-cell activation. Based upon previous studies in the
      literature, as well as accumulating evidence in allogeneic cells, I propose a
      multi-step model of in vivo metabolic reprogramming. In this model, a primary
      determinant of metabolic phenotype is the ubiquity and duration of antigen
      exposure. The implications of this model, as well as the future challenges and
      opportunities in studying T-cell metabolism, will be discussed. 

PMID- 25566256
TI  - Monitoring Circulating gammadelta T Cells in Cancer Patients to Optimize
      gammadelta T Cell-Based Immunotherapy.
AB  - The success of gammadelta T cell-based immunotherapy, where the cytotoxic
      activity of circulating gammadelta T lymphocytes is activated by nitrogen
      containing bisphosphonates (n-BP), or possibly by bispecific antibodies or the
      combination of both, requires a profound knowledge of patients' gammadelta T
      cells. A possible influence of radio- or chemotherapy on gammadelta T cells as
      well as their reported exhaustion after repetitive treatment with n-BP or their
      lack of response to various cancers can be easily determined by the monitoring
      assays described in this perspective article. Monitoring the absolute cell
      numbers of circulating gammadelta T cell subpopulations in small volumes of whole
      blood from cancer patients and determining gammadelta T cell cytotoxicity using
      the Real-Time Cell Analyzer can give a more comprehensive assessment of a
      personalized tumor treatment. Possible future directions such as the combined
      usage of n-BP or phosphorylated antigens together with bispecific antibodies that
      selectively target gammadelta T cells to tumor-associated antigens, will be
      discussed. Such strategies induce expansion and enhance gammadelta T cell
      cytotoxicity and might possibly avoid their exhaustion and overcome the
      immunosuppressive tumor microenvironment. 

PMID- 25566257
TI  - Immune system modeling and analysis.

PMID- 25566255
TI  - Epigenetic function of activation-induced cytidine deaminase and its link to
      lymphomagenesis.
AB  - Activation-induced cytidine deaminase (AID) is essential for somatic
      hypermutation and class switch recombination of immunoglobulin (Ig) genes during
      B cell maturation and immune response. Expression of AID is tightly regulated due
      to its mutagenic and recombinogenic potential, which is known to target not only
      Ig genes, but also non-Ig genes, contributing to lymphomagenesis. In recent
      years, a new epigenetic function of AID and its link to DNA demethylation came to
      light in several developmental systems. In this review, we summarize existing
      evidence linking deamination of unmodified and modified cytidine by AID to base
      excision repair and mismatch repair machinery resulting in passive or active
      removal of DNA methylation mark, with the focus on B cell biology. We also
      discuss potential contribution of AID-dependent DNA hypomethylation to
      lymphomagenesis. 

PMID- 25566258
TI  - Dendritic cells in dengue virus infection: targets of virus replication and
      mediators of immunity.
AB  - Dendritic cells (DCs) are sentinels of the immune system and detect pathogens at
      sites of entry, such as the skin. In addition to the ability of DCs to control
      infections directly via their innate immune functions, DCs help to prime adaptive
      B- and T-cell responses by processing and presenting antigen in lymphoid tissues.
      Infected Aedes aegypti or Aedes albopictus mosquitoes transmit the four dengue
      virus (DENV) serotypes to humans while probing for small blood vessels in the
      skin. DENV causes the most prevalent arthropod-borne viral disease in humans, yet
      no vaccine or specific therapeutic is currently licensed. Although primary DENV
      infection confers life-long protective immunity against re-infection with the
      same DENV serotype, secondary infection with a different DENV serotype can lead
      to increased disease severity via cross-reactive T-cells or enhancing antibodies.
      This review summarizes recent findings in humans and animal models about DENV
      infection of DCs, monocytes, and macrophages. We discuss the dual role of DCs as
      both targets of DENV replication and mediators of innate and adaptive immunity,
      and summarize immune evasion strategies whereby DENV impairs the function of
      infected DCs. We suggest that DCs play a key role in priming DENV-specific
      neutralizing or potentially harmful memory B- and T-cell responses, and that
      future DC-directed therapies may help induce protective memory responses and
      reduce dengue pathogenesis. 

PMID- 25566259
TI  - The Vgamma9Vdelta2 T Cell Antigen Receptor and Butyrophilin-3 A1: Models of
      Interaction, the Possibility of Co-Evolution, and the Case of Dendritic Epidermal
      T Cells.
AB  - Most circulating human gamma delta T cells are Vgamma9Vdelta2 T cells. Their
      hallmark is the expression of T cell antigen receptors (TCR) whose gamma-chains
      show a Vgamma9-JP (Vgamma2-Jgamma1.2) rearrangement and are paired with Vdelta2
      containing delta-chains, a dominant TCR configuration, which until recently
      seemed to occur in primates only. Vgamma9Vdelta2 T cells respond to
      phosphoantigens (PAg) such as (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate
      (HMBPP), which is produced by many pathogens and isopentenyl pyrophosphate (IPP),
      which accumulates in certain tumors or cells treated with aminobisphosphonates
      such as zoledronate. A prerequisite for PAg-induced activation is the contact of
      Vgamma9Vdelta2 T cells with cells expressing butyrophilin-3 A1 (BTN3A1). We will
      first critically review models of how BTN3 might act in PAg-mediated
      Vgamma9Vdelta2 T cell activation and then address putative co-evolution of
      Vgamma9, Vdelta2, and BTN3 genes. In those rodent and lagomorphs used as animal
      models, all three genes are lost but a data-base analysis showed that they
      emerged together with placental mammals. A strong concomitant conservation of
      functional Vgamma9, Vdelta2, and BTN3 genes in other species suggests co
      evolution of these three genes. A detailed analysis was performed for the new
      world camelid alpaca (Vicugna pacos). It provides an excellent candidate for a
      non-primate species with presumably functional Vgamma9Vdelta2 T cells since TCR
      rearrangements share features characteristic for PAg-reactive primate
      Vgamma9Vdelta2 TCR and proposed PAg-binding sites of BTN3A1 have been conserved.
      Finally, we analyze the possible functional relationship between the butyrophilin
      family member Skint1 and the gammadelta TCR-V genes used by murine dendritic
      epithelial T cells (DETC). Among placental mammals, we identify five rodents, the
      cow, a bat, and the cape golden mole as the only species concomitantly possessing
      potentially functional homologs of murine Vgamma3, Vdelta4 genes, and Skint1 gene
      and suggest to search for DETC like cells in these species. 

PMID- 25566261
TI  - Human Vdelta2(+) gammadelta T Cells Differentially Induce Maturation, Cytokine
      Production, and Alloreactive T Cell Stimulation by Dendritic Cells and B Cells.
AB  - Human gammadelta T cells expressing the Vgamma9Vdelta2 T cell receptor can induce
      maturation of dendritic cells (DC) into antigen-presenting cells (APC) and B
      cells into antibody-secreting plasma cells. Since B cells are capable of
      presenting antigens to T cells, we investigated if Vgamma9Vdelta2 T cells can
      influence antigen-presentation by these cells. We report that Vgamma9Vdelta2 T
      cells induced expression of CD86, HLA-DR, and CD40 by B cells and stimulated the
      release of IL-4, IL-6, TNF-alpha, and IgG, IgA, and IgM. Vgamma9Vdelta2 T cells
      also augmented the ability of B cells to stimulate proliferation but not IFN
      gamma or IL-4 release by alloreactive T cells. In contrast, Vgamma9Vdelta2 T
      cells induced expression of CD86 and HLA-DR and the release of IFN-gamma, IL-6,
      and TNF-alpha by DC and these DC stimulated proliferation and IFN-gamma
      production by conventional T cells. Furthermore, CD86, TNF-alpha, IFN-gamma, and
      cell contact were found to be important in DC activation by Vgamma9Vdelta2 T
      cells but not in the activation of B cells. These data suggest that
      Vgamma9Vdelta2 T cells can induce maturation of B cells and DC into APC, but
      while they prime DC to stimulate T helper 1 (TH1) responses, they drive
      maturation of B cells into APC that can stimulate different T cell responses.
      Thus, Vgamma9Vdelta2 T cells can control different arms of the immune system
      through selective activation of B cells and DC in vitro, which may have important
      applications in immunotherapy and for vaccine adjuvants. 

PMID- 25566260
TI  - Platelets and infection - an emerging role of platelets in viral infection.
AB  - Platelets are anucleate blood cells that play a crucial role in the maintenance
      of hemostasis. While platelet activation and elevated platelet counts
      (thrombocytosis) are associated with increased risk of thrombotic complications,
      low platelet counts (thrombocytopenia) and several platelet function disorders
      increase the risk of bleeding. Over the last years, more and more evidence has
      emerged that platelets and their activation state can also modulate innate and
      adaptive immune responses and low platelet counts have been identified as a
      surrogate marker for poor prognosis in septic patients. Viral infections often
      coincide with platelet activation. Host inflammatory responses result in the
      release of platelet activating mediators and a pro-oxidative and pro-coagulant
      environment, which favors platelet activation. However, viruses can also directly
      interact with platelets and megakaryocytes and modulate their function.
      Furthermore, platelets can be activated by viral antigen-antibody complexes and
      in response to some viruses B-lymphocytes also generate anti-platelet antibodies.
      All these processes contributing to platelet activation result in increased
      platelet consumption and removal and often lead to thrombocytopenia, which is
      frequently observed during viral infection. However, virus-induced platelet
      activation does not only modulate platelet count but also shape immune responses.
      Platelets and their released products have been reported to directly and
      indirectly suppress infection and to support virus persistence in response to
      certain viruses, making platelets a double-edged sword during viral infections.
      This review aims to summarize the current knowledge on platelet interaction with
      different types of viruses, the viral impact on platelet activation, and platelet
      mediated modulations of innate and adaptive immune responses. 

PMID- 25566262
TI  - Considerations for applying metabolomics to the analysis of extracellular
      vesicles.

PMID- 25566264
TI  - Emerging evidence for platelets as immune and inflammatory effector cells.
AB  - While traditionally recognized for their roles in hemostatic pathways, emerging
      evidence demonstrates that platelets have previously unrecognized, dynamic roles
      that span the immune continuum. These newly recognized platelet functions,
      including the secretion of immune mediators, interactions with endothelial cells,
      monocytes, and neutrophils, toll-like receptor (TLR) mediated responses, and
      induction of neutrophil extracellular trap formation, bridge thrombotic and
      inflammatory pathways and contribute to host defense mechanisms against invading
      pathogens. In this focused review, we highlight several of these emerging aspects
      of platelet biology and their implications in clinical infectious syndromes. 

PMID- 25566263
TI  - HLA Class Ib Molecules and Immune Cells in Pregnancy and Preeclampsia.
AB  - Despite decades of research, the highly prevalent pregnancy complication
      preeclampsia, "the disease of theories," has remained an enigma. Indeed, the
      etiology of preeclampsia is largely unknown. A compiling amount of studies
      indicates that the pathological basis involves a complex array of genetic
      predisposition and immunological maladaptation, and that a contribution from the
      mother, the father, and the fetus is likely to be important. The Human Leukocyte
      Antigen (HLA)-G is an increasing focus of research in relation to preeclampsia.
      The HLA-G molecule is primarily expressed by the extravillous trophoblast cells
      lining the placenta together with the two other HLA class Ib molecules, HLA-E and
      HLA-F. Soluble isoforms of HLA-G have been detected in the early endometrium, the
      matured cumulus-oocyte complex, maternal blood of pregnant women, in umbilical
      cord blood, and lately, in seminal plasma. HLA-G is believed to be involved in
      modulating immune responses in the context of vascular remodeling during
      pregnancy as well as in dampening potential harmful immune attacks raised against
      the semi-allogeneic fetus. In addition, HLA-G genetic variants are associated
      with both membrane-bound and soluble forms of HLA-G, and, in some studies, with
      preeclampsia. In this review, a genetic contribution from the mother, the father,
      and the fetus, together with the presence and function of various immune cells of
      relevance in pregnancy are reviewed in relation to HLA-G and preeclampsia. 

PMID- 25566265
TI  - Mixing Signals: Molecular Turn Ons and Turn Offs for Innate gammadelta T-Cells.
AB  - Lymphocytes of the gamma delta (gammadelta) T-cell lineage are evolutionary
      conserved and although they express rearranged antigen-specific receptors, a
      large proportion respond as innate effectors. gammadelta T-cells are poised to
      combat infection by responding rapidly to cytokine stimuli similar to innate
      lymphoid cells. This potential to initiate strong inflammatory responses
      necessitates that inhibitory signals are balanced with activation signals. Here,
      we discuss some of the key mechanisms that regulate the development, activation,
      and inhibition of innate gammadelta T-cells in light of recent evidence that the
      inhibitory immunoglobulin-superfamily member B and T lymphocyte attenuator
      restricts their differentiation and effector function. 

PMID- 25566267
TI  - Therapeutic potential of extracellular vesicles.

PMID- 25566268
TI  - Targeted Immunology for Prevention and Cure of VL.

PMID- 25566266
TI  - The role of nucleotides and purinergic signaling in apoptotic cell clearance -
      implications for chronic inflammatory diseases.
AB  - Billions of cells undergo apoptosis every day in healthy individuals. A prompt
      removal of dying cells prevents the release of pro-inflammatory intracellular
      content and progress to secondary necrosis. Thus, inappropriate clearance of
      apoptotic cells provokes autoimmunity and has been associated with many chronic
      inflammatory diseases. Recent studies have suggested that extracellular adenosine
      5'-triphosphate and related nucleotides play an important role in the apoptotic
      clearance process. Here, we review the current understanding of nucleotides and
      purinergic receptors in apoptotic cell clearance and the potential therapeutic
      targets of purinergic receptor subtypes in inflammatory conditions. 

PMID- 25566269
TI  - Manufacture of immunoglobulin products for patients with primary antibody
      deficiencies - the effect of processing conditions on product safety and
      efficacy.
AB  - Early preparations of immunoglobulin (Ig) manufactured from human plasma by
      ethanol (Cohn) fractionation were limited in their usefulness for substitution
      therapy in patients with primary antibody deficiencies (PAD), as Ig aggregates
      formed during manufacture resulted in severe systemic reactions in patients when
      given intravenously. Developments in manufacturing technology obviated this
      problem through the capacity to produce concentrated solutions of intact
      monomeric Ig, revolutionizing PAD treatment and improving patient life expectancy
      and quality of life. As the need for Ig has grown, manufacturers have refined
      further manufacturing technologies to improve yield from plasma and produce
      therapies, which are easier and less expensive to deliver. This has led to the
      substitution, partly or wholly, of ethanol precipitation by other techniques such
      as chromatography, and has also stimulated the production of highly concentrated
      solutions capable of rapid infusion. Ig products have been associated, since
      their inception, with certain adverse events, including infectious disease
      transmission, hemolysis, and thromboembolism. The introduction of standardized
      manufacturing processes and dedicated pathogen elimination steps has removed the
      risk of infectious disease, and the focus of attention has shifted to other
      problems, which appear to have increased over the past 5 years. These include
      hemolysis and thromboembolism, both the cause for substantial concern and the
      subject of recent regulatory scrutiny and actions. We review the development of
      manufacturing technology and the emerging evidence that changes for the
      optimization of yield and convenience has contributed to the recent incidents in
      certain adverse events. Industry measures under development will be discussed in
      terms of their potential to improve safety and optimize care for patients with
      PAD. 

PMID- 25566270
TI  - Nonhost resistance to rust pathogens - a continuation of continua.
AB  - The rust fungi (order: Pucciniales) are a group of widely distributed fungal
      plant pathogens, which can infect representatives of all vascular plant groups.
      Rust diseases significantly impact several crop species and considerable research
      focuses on understanding the basis of host specificity and nonhost resistance.
      Like many pathogens, rust fungi vary considerably in the number of hosts they can
      infect, such as wheat leaf rust (Puccinia triticina), which can only infect
      species in the genera Triticum and Aegilops, whereas Asian soybean rust
      (Phakopsora pachyrhizi) is known to infect over 95 species from over 42 genera. A
      greater understanding of the genetic basis determining host range has the
      potential to identify sources of durable resistance for agronomically important
      crops. Delimiting the boundary between host and nonhost has been complicated by
      the quantitative nature of phenotypes in the transition between these two states.
      Plant-pathogen interactions in this intermediate state are characterized either
      by (1) the majority of accessions of a species being resistant to the rust or (2)
      the rust only being able to partially complete key components of its life cycle.
      This leads to a continuum of disease phenotypes in the interaction with different
      plant species, observed as a range from compatibility (host) to complete immunity
      within a species (nonhost). In this review we will highlight how the quantitative
      nature of disease resistance in these intermediate interactions is caused by a
      continuum of defense barriers, which a pathogen needs to overcome for
      successfully establishing itself in the host. To illustrate continua as this
      underlying principle, we will discuss the advances that have been made in
      studying nonhost resistance towards rust pathogens, particularly cereal rust
      pathogens. 

PMID- 25566272
TI  - The impact of sulfate restriction on seed yield and quality of winter oilseed
      rape depends on the ability to remobilize sulfate from vegetative tissues to
      reproductive organs.
AB  - Our current knowledge about sulfur (S) management by winter oilseed rape to
      satisfy the S demand of developing seeds is still scarce, particularly in
      relation to S restriction. Our goals were to determine the physiological
      processes related to S use efficiency that led to maintain the seed yield and
      quality when S limitation occurred at the bolting or early flowering stages. To
      address these questions, a pulse-chase (34)SO(2-) 4 labeling method was carried
      out in order to study the S fluxes from uptake and remobilization at the whole
      plant level. In response of S limitation at the bolting or early flowering
      stages, the leaves are the most important source organ for S remobilization
      during reproductive stages. By combining (34)S-tracer with biochemical
      fractionation in order to separate sulfate from other S-compounds, it appeared
      that sulfate was the main form of S remobilized in leaves at reproductive stages
      and that tonoplastic SULTR4-type transporters were specifically involved in the
      sulfate remobilisation in case of low S availability. In response to S limitation
      at the bolting stage, the seed yield and quality were dramatically reduced
      compared to control plants. These data suggest that the increase of both S
      remobilization from source leaves and the root proliferation in order to maximize
      sulfate uptake capacities, were not sufficient to maintain the seed yield and
      quality. When S limitation occurred at the early flowering stage, oilseed rape
      can optimize the mobilization of sulfate reserves from vegetative organs (leaves
      and stem) to satisfy the demand of seeds and maintain the seed yield and quality.
      Our study also revealed that the stem may act as a transient storage organ for
      remobilized S coming from source leaves before its utilization by seeds. The
      physiological traits (S remobilization, root proliferation, transient S storage
      in stem) observed under S limitation could be used in breeding programs to select
      oilseed rape genotypes with high S use efficiency. 

PMID- 25566271
TI  - Evidence for lateral gene transfer (LGT) in the evolution of eubacteria-derived
      small GTPases in plant organelles.
AB  - The genomes of free-living bacteria frequently exchange genes via lateral gene
      transfer (LGT), which has played a major role in bacterial evolution. LGT also
      played a significant role in the acquisition of genes from non-cyanobacterial
      bacteria to the lineage of "primary" algae and land plants. Small GTPases are
      widely distributed among prokaryotes and eukaryotes. In this study, we inferred
      the evolutionary history of organelle-targeted small GTPases in plants.
      Arabidopsis thaliana contains at least one ortholog in seven subfamilies of OBG
      HflX-like and TrmE-Era-EngA-YihA-Septin-like GTPase superfamilies (together
      referred to as Era-like GTPases). Subcellular localization analysis of all Era
      like GTPases in Arabidopsis revealed that all 30 eubacteria-related GTPases are
      localized to chloroplasts and/or mitochondria, whereas archaea-related DRG and
      NOG1 are localized to the cytoplasm and nucleus, respectively, suggesting that
      chloroplast- and mitochondrion-localized GTPases are derived from the ancestral
      cyanobacterium and alpha-proteobacterium, respectively, through endosymbiotic
      gene transfer (EGT). However, phylogenetic analyses revealed that plant organelle
      GTPase evolution is rather complex. Among the eubacterium-related GTPases, only
      four localized to chloroplasts (including one dual targeting GTPase) and two
      localized to mitochondria were derived from cyanobacteria and alpha
      proteobacteria, respectively. Three other chloroplast-targeted GTPases were
      related to alpha-proteobacterial proteins, rather than to cyanobacterial GTPases.
      Furthermore, we found that four other GTPases showed neither cyanobacterial nor
      alpha-proteobacterial affiliation. Instead, these GTPases were closely related to
      clades from other eubacteria, such as Bacteroides (Era1, EngB-1, and EngB-2) and
      green non-sulfur bacteria (HflX). This study thus provides novel evidence that
      LGT significantly contributed to the evolution of organelle-targeted Era-like
      GTPases in plants. 

PMID- 25566273
TI  - Global transcriptome analysis of developing chickpea (Cicer arietinum L.) seeds.
AB  - Understanding developmental processes, especially in non-model crop plants, is
      extremely important in order to unravel unique mechanisms regulating development.
      Chickpea (C. arietinum L.) seeds are especially valued for their high
      carbohydrate and protein content. Therefore, in order to elucidate the mechanisms
      underlying seed development in chickpea, deep sequencing of transcriptomes from
      four developmental stages was undertaken. In this study, next generation
      sequencing platform was utilized to sequence the transcriptome of four distinct
      stages of seed development in chickpea. About 1.3 million reads were generated
      which were assembled into 51,099 unigenes by merging the de novo and reference
      assemblies. Functional annotation of the unigenes was carried out using the
      Uniprot, COG and KEGG databases. RPKM based digital expression analysis revealed
      specific gene activities at different stages of development which was validated
      using Real time PCR analysis. More than 90% of the unigenes were found to be
      expressed in at least one of the four seed tissues. DEGseq was used to determine
      differentially expressing genes which revealed that only 6.75% of the unigenes
      were differentially expressed at various stages. Homology based comparison
      revealed 17.5% of the unigenes to be putatively seed specific. Transcription
      factors were predicted based on HMM profiles built using TF sequences from five
      legume plants and analyzed for their differential expression during progression
      of seed development. Expression analysis of genes involved in biosynthesis of
      important secondary metabolites suggested that chickpea seeds can serve as a good
      source of antioxidants. Since transcriptomes are a valuable source of molecular
      markers like simple sequence repeats (SSRs), about 12,000 SSRs were mined in
      chickpea seed transcriptome and few of them were validated. In conclusion, this
      study will serve as a valuable resource for improved chickpea breeding. 

PMID- 25566274
TI  - Transport processes of the legume symbiosome membrane.
AB  - The symbiosome membrane (SM) is a physical barrier between the host plant and
      nitrogen-fixing bacteria in the legume:rhizobia symbiosis, and represents a
      regulated interface for the movement of solutes between the symbionts that is
      under plant control. The primary nutrient exchange across the SM is the transport
      of a carbon energy source from plant to bacteroid in exchange for fixed nitrogen.
      At a biochemical level two channels have been implicated in movement of fixed
      nitrogen across the SM and a uniporter that transports monovalent dicarboxylate
      ions has been characterized that would transport fixed carbon. The aquaporin
      NOD26 may provide a channel for ammonia, but the genes encoding the other
      transporters have not been identified. Transport of several other solutes,
      including calcium and potassium, have been demonstrated in isolated symbiosomes,
      and genes encoding transport systems for the movement of iron, nitrate, sulfate,
      and zinc in nodules have been identified. However, definitively matching
      transport activities with these genes has proved difficult and many further
      transport processes are expected on the SM to facilitate the movement of
      nutrients between the symbionts. Recently, work detailing the SM proteome in
      soybean has been completed, contributing significantly to the database of known
      SM proteins. This represents a valuable resource for the identification of
      transporter protein candidates, some of which may correspond to transport
      processes previously described, or to novel transport systems in the symbiosis.
      Putative transporters identified from the proteome include homologs of
      transporters of sulfate, calcium, peptides, and various metal ions. Here we
      review current knowledge of transport processes of the SM and discuss the
      requirements for additional transport routes of other nutrients exchanged in the
      symbiosis, with a focus on transport systems identified through the soybean SM
      proteome. 

PMID- 25566275
TI  - Polyphenol oxidase affects normal nodule development in red clover (Trifolium
      pratense L.).
AB  - Polyphenol oxidase (PPO) may have multiple functions in tissues depending on its
      cellular or tissue localization. Here we use PPO RNAi transformants of red clover
      (Trifolium pratense) to determine the role PPO plays in normal development of
      plants, and especially in N2-fixing nodules. In red clover, PPO was not essential
      for either growth or nodule production, or for nodule function in plants grown
      under optimal, N-free conditions. However, absence of PPO resulted in a more
      reduced environment in all tissues, as measured by redox potential, and caused
      subtle developmental changes in nodules. Leaves and, to a lesser extent nodules,
      lacking PPO tended to accumulate phenolic compounds. A comparison of nodules of
      two representative contrasting clones by microscopy revealed that nodules lacking
      PPO were morphologically and anatomically subtly altered, and that phenolics
      accumulated in different cells and tissues. Developing nodules lacking PPO were
      longer, and there were more cell layers within the squashed cell layer (SCL), but
      the walls of these cells were less thickened and the cells were less squashed.
      Within the N2-fixing zone, bacteroids appeared more granular and were less
      tightly packed together, and were similar to developmentally compromised
      bacteroids elicited by catalase mutant rhizobia reported elsewhere. 

PMID- 25566276
TI  - The phosphate transporter PHT4;1 is a salicylic acid regulator likely controlled
      by the circadian clock protein CCA1.
AB  - The small phenolic compound salicylic acid (SA) plays a critical role in plant
      defense against broad-spectrum of pathogens. The phosphate transporter gene
      PHT4;1 was previously shown to affect SA-mediated defense and its expression is
      regulated by the circadian clock. To further understand how PHT4;1 affects SA
      accumulation, here we analyzed the genetic interactions between the gain-of
      function mutant pht4;1-1 and several known SA mutants, including sid2-1, ald1-1,
      eds5-3, and pad4-1. The genetic analysis was conducted in the acd6-1 background
      since the change of acd6-1 dwarfism can be used as a convenient readout for the
      change of defense levels caused by impairments in some SA genes. We found that
      compared with the corresponding double mutants, the triple mutants acd6-1pht4;1
      1ald1-1, acd6-1pht4;1-1eds5-3, and acd6-1pht4;1-1pad4-1 accumulated lower levels
      of SA and PR1 transcripts, suggesting that PHT4;1 contributes to acd6-1-conferred
      defense phenotypes independently of these known SA regulators. Although some
      triple mutants had wild type (wt)-like levels of SA and PR1 transcripts, these
      plants were smaller than wt and displayed minor cell death, suggesting that
      additional regulatory pathways contribute to acd6-1-conferred dwarfism and cell
      death. Our data further showed that circadian expression of PHT4;1 was dependent
      on CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), a central oscillator component of
      Arabidopsis circadian clock. Recombinant CCA1 protein was demonstrated to bind to
      the PHT4;1 promoter in electrophoretic mobility shift assays, suggesting a direct
      transcriptional regulation of PHT4;1 by CCA1. Together these results indicate
      that PHT4;1 is a SA regulator acting independently of several known SA genes and
      they also implicate a role of the circadian clock mediated by CCA1 in regulating
      phosphate transport and/or innate immunity in Arabidopsis. 

PMID- 25566277
TI  - Transcript profiles of maize embryo sacs and preliminary identification of genes
      involved in the embryo sac-pollen tube interaction.
AB  - The embryo sac, the female gametophyte of flowering plants, plays important roles
      in the pollination and fertilization process. Maize (Zea mays L.) is a model
      monocot, but little is known about the interactions between its embryo sac and
      the pollen tube. In this study, we compared the transcript profiles of mature
      embryo sacs, mature embryo sacs 14-16 h after pollination, and mature nucelli.
      Comparing the transcript profiles of the embryo sacs before and after the entry
      of the pollen tube, we identified 3467 differentially expressed transcripts (3382
      differentially expressed genes; DEGs). The DEGs were grouped into 22 functional
      categories. Among the DEGs, 221 genes were induced upon the entry of the pollen
      tube, and many of them encoded proteins involved in RNA binding, processing, and
      transcription, signaling, miscellaneous enzyme family processes, and lipid
      metabolism processes. Genes in the DEG dataset were grouped into 17 classes in a
      gene ontology enrichment analysis. The DEGs included many genes encoding proteins
      involved in protein amino acid phosphorylation and protein ubiquitination,
      implying that these processes might play important roles in the embryo sac-pollen
      tube interaction. Additionally, our analyses indicate that the expression of 112
      genes encoding cysteine-rich proteins (CRPs) is induced during pollination and
      fertilization. The CRPs likely regulate pollen tube guidance and embryo sac
      development. These results provide important information on the genes involved in
      the embryo sac-pollen tube interaction in maize. 

PMID- 25566278
TI  - Effects of high NH(+) 4 on K(+) uptake, culm mechanical strength and grain
      filling in wheat.
AB  - It is well established that a high external NH(+) 4 concentration depresses many
      processes in plant development, but the underlying mechanisms are still not well
      understood. To determine whether the negative effects of high levels of NH(+) 4
      are related to competitive cation uptake, wheat was grown in a field with
      moderate (18 g N m(-2)) and high (30 g N m(-2)) supplies of NH(+) 4 in the
      presence or absence of additional K(+) (6 g K2O m(-2)) to examine culm mechanical
      strength, the main components of the vascular bundle, nitrogen (N) remobilization
      and the grain-filling rate. The results indicated that an excessive supply of
      NH(+) 4 significantly decreased culm mechanical strength, the cellulose and
      lignin contents of vascular bundles, the N remobilization efficiency (NRE) and
      the grain-filling rate compared with a moderate level of NH(+) 4. The additional
      provision of K(+) considerably alleviated these negative effects of high NH(+) 4,
      resulting in a 19.41-26.95% increase in culm mechanical strength during grain
      filling and a 34.59% increase in the NRE. An assay using the scanning ion
      selective electrode technique (SIET) showed that the net rate of transmembrane
      K(+) influx decreased by 84.62%, and measurements using flame photometry
      demonstrated that the K(+) content decreased by 36.13% in wheat plants subjected
      to high NH(+) 4. This study indicates that the effects of high NH(+) 4 on culm
      mechanical strength, cellulose and lignin contents, the NRE and the grain-filling
      rate are probably associated with inhibition of K(+) uptake in wheat. 

PMID- 25566279
TI  - The significance of glucosinolates for sulfur storage in Brassicaceae seedlings.
AB  - Brassica juncea seedlings contained a twofold higher glucosinolate content than
      B. rapa and these secondary sulfur compounds accounted for up to 30% of the
      organic sulfur fraction. The glucosinolate content was not affected by H2S and
      SO2 exposure, demonstrating that these sulfur compounds did not form a sink for
      excessive atmospheric supplied sulfur. Upon sulfate deprivation, the foliarly
      absorbed H2S and SO2 replaced sulfate as the sulfur source for growth of B.
      juncea and B. rapa seedlings. The glucosinolate content was decreased in sulfate
      deprived plants, though its proportion of organic sulfur fraction was higher than
      that of sulfate-sufficient plants, both in absence and presence of H2S and SO2.
      The significance of myrosinase in the in situ turnover in these secondary sulfur
      compounds needs to be questioned, since there was no direct co-regulation between
      the content of glucosinolates and the transcript level and activity of
      myrosinase. Evidently, glucosinolates cannot be considered as sulfur storage
      compounds upon exposure to excessive atmospheric sulfur and are unlikely to be
      involved in the re-distribution of sulfur in B. juncea and B. rapa seedlings upon
      sulfate deprivation. 

PMID- 25566280
TI  - Long distance movement of an Arabidopsis Translationally Controlled Tumor Protein
      (AtTCTP2) mRNA and protein in tobacco.
AB  - Translationally Controlled Tumor Protein (TCTP) is an almost ubiquitous protein
      found in eukaryotes, fundamental for the regulation of development and general
      growth. The multiple functions of TCTP have been inferred from its involvement in
      several cell pathways, but the specific function of TCTP is still not known in
      detail. On the other hand, TCTP seems to respond to a plethora of external
      signals, and appears to be regulated at the transcriptional and/or translational
      levels by mechanisms yet to be determined. In the present work, we analyzed the
      capacity of AtTCTP2 gene products (mRNA and protein) to translocate long distance
      through tobacco heterografts (transgenic/WT and WT/transgenic). The results
      indicate that both AtTCTP2 mRNA and protein are capable of moving long distance
      in both directions (stock-scion and scion-stock) with a tendency for movement
      from source to sink tissue (stock to scion). Interestingly, aerial roots emerged
      only in heterografts where the protein was detected in both stock and scion,
      suggesting a correlation between the presence of AtTCTP2 and aerial root
      appearance. More detailed analysis showed that these aerial roots harbored the
      transgene and expressed both transcript and protein. In addition, the protein
      localization pattern in transgenic aerial and primary roots was basically the
      same, indicating specific nuclear destination in roots, but also in leaves. These
      findings provide an approach to understand the role of long-distance movement in
      the function of plant TCTPs, supporting the notion that some of these act in a
      non-cell autonomous manner, as the human counterpart, the Histamine Releasing
      Factor (HRF). 

PMID- 25566281
TI  - Metabolite changes in conifer buds and needles during forced bud break in Norway
      spruce (Picea abies) and European silver fir (Abies alba).
AB  - Environmental changes such as early spring and warm spells induce bud burst and
      photosynthetic processes in cold-acclimated coniferous trees and consequently,
      cellular metabolism in overwintering needles and buds. The purpose of the study
      was to examine metabolism in conifers under forced deacclimation (artificially
      induced spring) by exposing shoots of Picea abies (boreal species) and Abies alba
      (temperate species) to a greenhouse environment (22 degrees C, 16/8 h D/N cycle)
      over a 9 weeks period. Each week, we scored bud opening and collected samples for
      GC/MS-based metabolite profiling. We detected a total of 169 assigned metabolites
      and 80 identified metabolites, comprising compounds such as mono- and
      disaccharides, Krebs cycle acids, amino acids, polyols, phenolics, and
      phosphorylated structures. Untargeted multivariate statistical analysis based on
      PCA and cluster analysis segregated samples by species, tissue type, and stage of
      tissue deacclimations. Similar patterns of metabolic regulation in both species
      were observed in buds (amino acids, Krebs cycle acids) and needles (hexoses,
      pentoses, and Krebs cycle acids). Based on correlation of bud opening score with
      compound levels, distinct metabolites could be associated with bud and shoot
      development, including amino acids, sugars, and acids with known osmolyte
      function, and secondary metabolites. This study has shed light on how elevated
      temperature affects metabolism in buds and needles of conifer species during the
      deacclimation phase, and contributes to the discussion about how phenological
      characters in conifers may respond to future global warming. 

PMID- 25566282
TI  - plantDARIO: web based quantitative and qualitative analysis of small RNA-seq data
      in plants.
AB  - High-throughput sequencing techniques have made it possible to assay an
      organism's entire repertoire of small non-coding RNAs (ncRNAs) in an efficient
      and cost-effective manner. The moderate size of small RNA-seq datasets makes it
      feasible to provide free web services to the research community that provide many
      basic features of a small RNA-seq analysis, including quality control, read
      normalization, ncRNA quantification, and the prediction of putative novel ncRNAs.
      DARIO is one such system that so far has been focussed on animals. Here we
      introduce an extension of this system to plant short non-coding RNAs (sncRNAs).
      It includes major modifications to cope with plant-specific sncRNA processing.
      The current version of plantDARIO covers analyses of mapping files, small RNA-seq
      quality control, expression analyses of annotated sncRNAs, including the
      prediction of novel miRNAs and snoRNAs from unknown expressed loci and expression
      analyses of user-defined loci. At present Arabidopsis thaliana, Beta vulgaris,
      and Solanum lycopersicum are covered. The web tool links to a plant specific
      visualization browser to display the read distribution of the analyzed sample.
      The easy-to-use platform of plantDARIO quantifies RNA expression of annotated
      sncRNAs from different sncRNA databases together with new sncRNAs, annotated by
      our group. The plantDARIO website can be accessed at http://plantdario.bioinf.uni
      leipzig.de/. 

PMID- 25566284
TI  - Transceptors at the boundary of nutrient transporters and receptors: a new role
      for Arabidopsis SULTR1;2 in sulfur sensing.
AB  - Plants have evolved a sophisticated mechanism to sense the extracellular sulfur
      (S) status so that sulfate transport and S assimilation/metabolism can be
      coordinated. Genetic, biochemical, and molecular studies in Arabidopsis over the
      past 10 years have started to shed some light on the regulatory mechanism of the
      S response. Key advances in transcriptional regulation (SLIM1, MYB, and miR395),
      involvement of hormones (auxin, cytokinin, and abscisic acid) and identification
      of putative sensors (OASTL and SULTR1;2) are highlighted here. Although our
      current view of S nutrient sensing and signaling remains fragmented, it is
      anticipated that through further studies a sensing and signaling network will be
      revealed in the near future. 

PMID- 25566285
TI  - Proteomics of stress responses in wheat and barley-search for potential protein
      markers of stress tolerance.
AB  - Wheat (Triticum aestivum; T. durum) and barley (Hordeum vulgare) agricultural
      production is severely limited by various abiotic and biotic stress factors.
      Proteins are directly involved in plant stress response so it is important to
      study proteome changes under various stress conditions. Generally, both abiotic
      and biotic stress factors induce profound alterations in protein network covering
      signaling, energy metabolism (glycolysis, Krebs cycle, ATP biosynthesis,
      photosynthesis), storage proteins, protein metabolism, several other biosynthetic
      pathways (e.g., S-adenosylmethionine metabolism, lignin metabolism), transport
      proteins, proteins involved in protein folding and chaperone activities, other
      protective proteins (LEA, PR proteins), ROS scavenging enzymes as well as
      proteins affecting regulation of plant growth and development. Proteins which
      have been reported to reveal significant differences in their relative abundance
      or posttranslational modifications between wheat, barley or related species
      genotypes under stress conditions are listed and their potential role in
      underlying the differential stress response is discussed. In conclusion,
      potential future roles of the results of proteomic studies in practical
      applications such as breeding for an enhanced stress tolerance and the
      possibilities to test and use protein markers in the breeding are suggested. 

PMID- 25566283
TI  - Molecular locks and keys: the role of small molecules in phytohormone research.
AB  - Plant adaptation, growth and development rely on the integration of many
      environmental and endogenous signals that collectively determine the overall
      plant phenotypic plasticity. Plant signaling molecules, also known as
      phytohormones, are fundamental to this process. These molecules act at low
      concentrations and regulate multiple aspects of plant fitness and development via
      complex signaling networks. By its nature, phytohormone research lies at the
      interface between chemistry and biology. Classically, the scientific community
      has always used synthetic phytohormones and analogs to study hormone functions
      and responses. However, recent advances in synthetic and combinational chemistry,
      have allowed a new field, plant chemical biology, to emerge and this has provided
      a powerful tool with which to study phytohormone function. Plant chemical biology
      is helping to address some of the most enduring questions in phytohormone
      research such as: Are there still undiscovered plant hormones? How can we
      identify novel signaling molecules? How can plants activate specific hormone
      responses in a tissue-specific manner? How can we modulate hormone responses in
      one developmental context without inducing detrimental effects on other
      processes? The chemical genomics approaches rely on the identification of small
      molecules modulating different biological processes and have recently identified
      active forms of plant hormones and molecules regulating many aspects of hormone
      synthesis, transport and response. We envision that the field of chemical
      genomics will continue to provide novel molecules able to elucidate specific
      aspects of hormone-mediated mechanisms. In addition, compounds blocking specific
      responses could uncover how complex biological responses are regulated. As we
      gain information about such compounds we can design small alterations to the
      chemical structure to further alter specificity, enhance affinity or modulate the
      activity of these compounds. 

PMID- 25566287
TI  - Biological mode of action of a nitrophenolates-based biostimulant: case study.
AB  - The challenges facing modern plant production involve (i) responding to the
      demand for food and resources of plant origin from the world's rapidly growing
      population, (ii) coping with the negative impact of stressful conditions mainly
      due to anthropopressure, and (iii) meeting consumers' new requirements and
      preferences for food that is high in nutritive value, natural, and free from
      harmful chemical additives. Despite employing the most modern plant cultivation
      technologies and the progress that has been made in breeding programs, the
      genetically-determined crop potential is still far from being fully exploited.
      Consequently yield and quality are often reduced, making production less, both
      profitable and attractive. There is an increasing desire to reduce the chemical
      input in agriculture and there has been a change toward integrated plant
      management and sustainable, environmentally-friendly systems. Biostimulants are a
      category of relatively new products of diverse formulations that positively
      affect a plant's vital processes and whose impact is usually more evident under
      stressful conditions. In this paper, information is provided on the mode of
      action of a nitrophenolates-based biostimulant, Atonik, in model species and
      economically important crops grown under both field and controlled conditions in
      a growth chamber. The effects of Atonik on plant morphology, physiology,
      biochemistry (crops and model plant) and yield and yield parameters (crops) is
      demonstrated. Effects of other biostimulants on studied in this work
      processes/parameters are also presented in discussion. 

PMID- 25566286
TI  - The poplar Phi class glutathione transferase: expression, activity and structure
      of GSTF1.
AB  - Glutathione transferases (GSTs) constitute a superfamily of enzymes with
      essential roles in cellular detoxification and secondary metabolism in plants as
      in other organisms. Several plant GSTs, including those of the Phi class (GSTFs),
      require a conserved catalytic serine residue to perform glutathione (GSH)
      conjugation reactions. Genomic analyses revealed that terrestrial plants have
      around ten GSTFs, eight in the Populus trichocarpa genome, but their
      physiological functions and substrates are mostly unknown. Transcript expression
      analyses showed a predominant expression of all genes both in reproductive
      (female flowers, fruits, floral buds) and vegetative organs (leaves, petioles).
      Here, we show that the recombinant poplar GSTF1 (PttGSTF1) possesses peroxidase
      activity toward cumene hydroperoxide and GSH-conjugation activity toward model
      substrates such as 2,4-dinitrochlorobenzene, benzyl and phenetyl isothiocyanate,
      4-nitrophenyl butyrate and 4-hydroxy-2-nonenal but interestingly not on
      previously identified GSTF-class substrates. In accordance with analytical gel
      filtration data, crystal structure of PttGSTF1 showed a canonical dimeric
      organization with bound GSH or 2-(N-morpholino)ethanesulfonic acid molecules. The
      structure of these protein-substrate complexes allowed delineating the residues
      contributing to both the G and H sites that form the active site cavity. In sum,
      the presence of GSTF1 transcripts and proteins in most poplar organs especially
      those rich in secondary metabolites such as flowers and fruits, together with its
      GSH-conjugation activity and its documented stress-responsive expression suggest
      that its function is associated with the catalytic transformation of metabolites
      and/or peroxide removal rather than with ligandin properties as previously
      reported for other GSTFs. 

PMID- 25566288
TI  - Charring temperatures are driven by the fuel types burned in a peatland wildfire.
AB  - Peatlands represent a globally important carbon store; however, the human
      exploitation of this ecosystem is increasing both the frequency and severity of
      fires on drained peatlands. Yet, the interactions between the hydrological
      conditions (ecotopes), the fuel types being burned, the burn severity, and the
      charring temperatures (pyrolysis intensity) remain poorly understood. Here we
      present a post-burn assessment of a fire on a lowland raised bog in Co. Offaly,
      Ireland (All Saints Bog). Three burn severities were identified in the field
      (light, moderate, and deeply burned), and surface charcoals were taken from 17
      sites across all burn severities. Charcoals were classified into two fuel type
      categories (either ground or aboveground fuel) and the reflectance of each
      charcoal particle was measured under oil using reflectance microscopy. Charcoal
      reflectance shows a positive relationship with charring temperature and as such
      can be used as a temperature proxy to reconstruct minimum charring temperatures
      after a fire event. Resulting median reflectance values for ground fuels are 1.09
      +/- 0.32%Romedian, corresponding to estimated minimum charring temperatures of
      447 degrees C +/- 49 degrees C. In contrast, the median charring temperatures of
      aboveground fuels were found to be considerably higher, 646 degrees C +/- 73
      degrees C (3.58 +/- 0.77%Romedian). A mixed-effects modeling approach was used to
      demonstrate that the interaction effects of burn severity, as well as ecotope
      classes, on the charcoal reflectance is small compared to the main effect of fuel
      type. Our findings reveal that the different fuel types on raised bogs are
      capable of charring at different temperatures within the same fire, and that the
      pyrolysis intensity of the fire on All Saints Bog was primarily driven by the
      fuel types burning, with only a weak association to the burn severity or ecotope
      classes. 

PMID- 25566289
TI  - Breeding for resistances to Ralstonia solanacearum.
AB  - Ralstonia solanacearum is one of the most devastating bacterial plant pathogens
      due to its large host range, worldwide geographic distribution and persistence in
      fields. This soilborne pathogen is the causal agent of bacterial wilt and it can
      infect major agricultural crops thereby reducing significantly their yield. To
      favor infection, the bacterium delivers, through the type three secretion system,
      effectors that manipulate plant immunity. In this review, the relative efficiency
      of control strategies and existing resistances to R. solanacearum will be
      presented. Then, the genetic and molecular insights gained from the study of
      bacterial wilt in model plants will be described. Finally, I will explore how the
      knowledge gathered from unraveling avirulence and virulence mechanisms of R.
      solanacearum effectors could help to develop more durable resistances in crop
      plants toward this destructive pathogen. 

PMID- 25566290
TI  - Soybean and casein hydrolysates induce grapevine immune responses and resistance
      against Plasmopara viticola.
AB  - Plasmopara viticola, the causal agent of grapevine downy mildew, is one of the
      most devastating grape pathogen in Europe and North America. Although
      phytochemicals are used to control pathogen infections, the appearance of
      resistant strains and the concern for possible adverse effects on environment and
      human health are increasing the search for alternative strategies. In the present
      investigation, we successfully tested two protein hydrolysates from soybean (soy)
      and casein (cas) to trigger grapevine resistance against P. viticola. On Vitis
      vinifera cv. Marselan plants, the application of soy and cas reduced the infected
      leaf surface by 76 and 63%, as compared to the control, respectively. Since both
      hydrolysates might trigger the plant immunity, we investigated their ability to
      elicit grapevine defense responses. On grapevine cell suspensions, a different
      free cytosolic calcium signature was recorded for each hydrolysate, whereas a
      similar transient phosphorylation of two MAP kinases of 45 and 49 kDa was
      observed. These signaling events were followed by transcriptome reprogramming,
      including the up-regulation of defense genes encoding pathogenesis-related (PR)
      proteins and the stilbene synthase enzyme responsible for the biosynthesis of
      resveratrol, the main grapevine phytoalexin. Liquid chromatography analyses
      confirmed the production of resveratrol and its dimer metabolites, delta- and
      epsilon-viniferins. Overall, soy effects were more pronounced as compared to the
      cas ones. Both hydrolysates proved to act as elicitors to enhance grapevine
      immunity against pathogen attack. 

PMID- 25566291
TI  - Field and controlled environment measurements show strong seasonal acclimation in
      photosynthesis and respiration potential in boreal Scots pine.
AB  - Understanding the seasonality of photosynthesis in boreal evergreen trees and its
      control by the environment requires separation of the instantaneous and slow
      responses, as well as the dynamics of light reactions, carbon reactions, and
      respiration. We determined the seasonality of photosynthetic light response and
      respiration parameters of Scots pine (Pinus sylvestris L.) in the field in
      southern Finland and in controlled laboratory conditions. CO2 exchange and
      chlorophyll fluorescence were measured in the field using a continuously operated
      automated chamber setup and fluorescence monitoring systems. We also carried out
      monthly measurements of photosynthetic light, CO2 and temperature responses in
      standard conditions with a portable IRGA and fluorometer instrument. The field
      and response measurements indicated strong seasonal variability in the state of
      the photosynthetic machinery with a deep downregulation during winter. Despite
      the downregulation, the photosynthetic machinery retained a significant capacity
      during winter, which was not visible in the field measurements. Light-saturated
      photosynthesis (P sat) and the initial slope of the photosynthetic light response
      (alpha) obtained in standard conditions were up to 20% of their respective
      summertime values. Respiration also showed seasonal acclimation with peak values
      of respiration in standard temperature in spring and decline in autumn. Spring
      recovery of all photosynthetic parameters could be predicted with temperature
      history. On the other hand, the operating quantum yield of photosystem II and the
      initial slope of photosynthetic light response stayed almost at the summertime
      level until late autumn while at the same time P sat decreased following the
      prevailing temperature. Comparison of photosynthetic parameters with the
      environmental drivers suggests that light and minimum temperature are also
      decisive factors in the seasonal acclimation of photosynthesis in boreal
      evergreen trees. 

PMID- 25566293
TI  - Exogenous abscisic acid application decreases cadmium accumulation in Arabidopsis
      plants, which is associated with the inhibition of IRT1-mediated cadmium uptake.
AB  - Cadmium (Cd) contamination of agricultural soils is an increasingly serious
      problem. Measures need to be developed to minimize Cd entering the human food
      chain from contaminated soils. We report here that, under Cd exposure condition,
      application with low doses of (0.1-0.5 MUM) abscisic acid (ABA) clearly inhibited
      Cd uptake by roots and decreased Cd level in Arabidopsis wild-type plants (Col
      0). Expression of IRT1 in roots was also strongly inhibited by ABA treatment.
      Decrease in Cd uptake and the inhibition of IRT1 expression were clearly lesser
      pronounced in an ABA-insensitive double mutant snrk2.2/2.3 than in the Col-0 in
      response to ABA application. The ABA-decreased Cd uptake was found to correlate
      with the ABA-inhibited IRT1 expression in the roots of Col-0 plants fed two
      different levels of iron. Furthermore, the Cd uptake of irt1 mutants was barely
      affected by ABA application. These results indicated that inhibition of IRT1
      expression is involved in the decrease of Cd uptake in response to exogenous ABA
      application. Interestingly, ABA application increased the iron level in both Col
      0 plants and irt1 mutants, suggesting that ABA-increased Fe acquisition does not
      depend on the IRT1 function, but on the contrary, the ABA-mediated inhibition of
      IRT1 expression may be due to the elevation of iron level in plants. From our
      results, we concluded that ABA application might increase iron acquisition,
      followed by the decrease in Cd uptake by inhibition of IRT1 activity. Thus, for
      crop production in Cd contaminated soils, developing techniques based on ABA
      application potentially is a promising approach for reducing Cd accumulation in
      edible organs in plants. 

PMID- 25566292
TI  - Light as stress factor to plant roots - case of root halotropism.
AB  - Despite growing underground, largely in darkness, roots emerge to be very
      sensitive to light. Recently, several important papers have been published which
      reveal that plant roots not only express all known light receptors but also that
      their growth, physiology and adaptive stress responses are light-sensitive. In
      Arabidopsis, illumination of roots speeds-up root growth via reactive oxygen
      species-mediated and F-actin dependent process. On the other hand, keeping
      Arabidopsis roots in darkness alters F-actin distribution, polar localization of
      PIN proteins as well as polar transport of auxin. Several signaling components
      activated by phytohormones are overlapping with light-related signaling cascade.
      We demonstrated that the sensitivity of roots to salinity is altered in the light
      grown Arabidopsis roots. Particularly, light-exposed roots are less effective in
      their salt-avoidance behavior known as root halotropism. Here we discuss these
      new aspects of light-mediated root behavior from cellular, physiological and
      evolutionary perspectives. 

PMID- 25566295
TI  - The role of bacteria and mycorrhiza in plant sulfur supply.
AB  - Plant growth is highly dependent on bacteria, saprophytic, and mycorrhizal fungi
      which facilitate the cycling and mobilization of nutrients. Over 95% of the
      sulfur (S) in soil is present in an organic form. Sulfate-esters and sulfonates,
      the major forms of organo-S in soils, arise through deposition of biological
      material and are transformed through subsequent humification. Fungi and bacteria
      release S from sulfate-esters using sulfatases, however, release of S from
      sulfonates is catalyzed by a bacterial multi-component mono-oxygenase system. The
      asfA gene is used as a key marker in this desulfonation process to study
      sulfonatase activity in soil bacteria identified as Variovorax, Polaromonas,
      Acidovorax, and Rhodococcus. The rhizosphere is regarded as a hot spot for
      microbial activity and recent studies indicate that this is also the case for the
      mycorrhizosphere where bacteria may attach to the fungal hyphae capable of
      mobilizing organo-S. While current evidence is not showing sulfatase and
      sulfonatase activity in arbuscular mycorrhiza, their effect on the expression of
      plant host sulfate transporters is documented. A revision of the role of
      bacteria, fungi and the interactions between soil bacteria and mycorrhiza in
      plant S supply was conducted. 

PMID- 25566294
TI  - The C-terminus of Bienertia sinuspersici Toc159 contains essential elements for
      its targeting and anchorage to the chloroplast outer membrane.
AB  - Most nucleus-encoded chloroplast proteins rely on an N-terminal transit peptide
      (TP) as a post-translational sorting signal for directing them to the organelle.
      Although Toc159 is known to be a receptor for specific preprotein TPs at the
      chloroplast surface, the mechanism for its own targeting and integration into the
      chloroplast outer membrane is not completely understood. In a previous study, we
      identified a novel TP-like sorting signal at the C-terminus (CT) of a Toc159
      homolog from the single-cell C4 species, Bienertia sinuspersici. In the current
      study, we have extended our understanding of the sorting signal using transient
      expression of fluorescently-tagged fusion proteins of variable-length, and with
      truncated and swapped versions of the CT. As was shown in the earlier study, the
      56 residues of the CT contain crucial sorting information for reversible
      interaction of the receptor with the chloroplast envelope. Extension of this
      region to 100 residues in the current study stabilized the interaction via
      membrane integration, as demonstrated by more prominent plastid-associated
      signals and resistance of the fusion protein to alkaline extraction. Despite a
      high degree of sequence similarity, the plastid localization signals of the
      equivalent CT regions of Arabidopsis thaliana Toc159 homologs were not as strong
      as that of the B. sinuspersici counterparts. Together with computational and
      circular dichroism analyses of the CT domain structures, our data provide
      insights into the critical elements of the CT for the efficient targeting and
      anchorage of Toc159 receptors to the dimorphic chloroplasts in the single-cell C4
      species. 

PMID- 25566297
TI  - High relative air humidity influences mineral accumulation and growth in iron
      deficient soybean plants.
AB  - Iron (Fe) deficiency chlorosis (IDC) in soybean results in severe yield losses.
      Cultivar selection is the most commonly used strategy to avoid IDC but there is a
      clear interaction between genotype and the environment; therefore, the search for
      quick and reliable tools to control this nutrient deficiency is essential.
      Several studies showed that relative humidity (RH) may influence the long
      distance transport of mineral elements and the nutrient status of plants. Thus,
      we decided to analyze the response of an "Fe-efficient" (EF) and an "Fe
      inefficient" (INF) soybean accession grown under Fe-sufficient and deficient
      conditions under low (60%) and high (90%) RH, evaluating morphological, and
      physiological parameters. Furthermore, the mineral content of different plant
      organs was analyzed. Our results showed beneficial effects of high RH in
      alleviating IDC symptoms as seen by increased SPAD values, higher plant dry
      weight (DW), increased plant height, root length, and leaf area. This positive
      effect of RH in reducing IDC symptoms was more pronounced in the EF accession.
      Also, Fe content in the different plant organs of the EF accession grown under
      deficient conditions increased with RH. The lower partitioning of Fe to roots and
      stems of the EF accessions relative to dry matter also supported our hypothesis,
      suggesting a greater capacity of this accession in Fe translocation to the aerial
      parts under Fe deficient conditions, when grown under high RH. 

PMID- 25566296
TI  - Integration of a constraint-based metabolic model of Brassica napus developing
      seeds with (13)C-metabolic flux analysis.
AB  - The use of large-scale or genome-scale metabolic reconstructions for modeling and
      simulation of plant metabolism and integration of those models with large-scale
      omics and experimental flux data is becoming increasingly important in plant
      metabolic research. Here we report an updated version of bna572, a bottom-up
      reconstruction of oilseed rape (Brassica napus L.; Brassicaceae) developing seeds
      with emphasis on representation of biomass-component biosynthesis. New features
      include additional seed-relevant pathways for isoprenoid, sterol,
      phenylpropanoid, flavonoid, and choline biosynthesis. Being now based on
      standardized data formats and procedures for model reconstruction, bna572+ is
      available as a COBRA-compliant Systems Biology Markup Language (SBML) model and
      conforms to the Minimum Information Requested in the Annotation of Biochemical
      Models (MIRIAM) standards for annotation of external data resources. Bna572+
      contains 966 genes, 671 reactions, and 666 metabolites distributed among 11
      subcellular compartments. It is referenced to the Arabidopsis thaliana genome,
      with gene-protein-reaction (GPR) associations resolving subcellular localization.
      Detailed mass and charge balancing and confidence scoring were applied to all
      reactions. Using B. napus seed specific transcriptome data, expression was
      verified for 78% of bna572+ genes and 97% of reactions. Alongside bna572+ we also
      present a revised carbon centric model for (13)C-Metabolic Flux Analysis ((13)C
      MFA) with all its reactions being referenced to bna572+ based on linear
      projections. By integration of flux ratio constraints obtained from (13)C-MFA and
      by elimination of infinite flux bounds around thermodynamically infeasible loops
      based on COBRA loopless methods, we demonstrate improvements in predictive power
      of Flux Variability Analysis (FVA). Using this combined approach we characterize
      the difference in metabolic flux of developing seeds of two B. napus genotypes
      contrasting in starch and oil content. 

PMID- 25566298
TI  - Plant grafting: new mechanisms, evolutionary implications.
AB  - Grafting, an old plant propagation practice, is still widely used with fruit
      trees and in recent decades also with vegetables. Taxonomic proximity is a
      general prerequisite for successful graft-take and long-term survival of the
      grafted, composite plant. However, the mechanisms underlying interspecific graft
      incompatibility are as yet insufficiently understood. Hormonal signals, auxin in
      particular, are believed to play an important role in the wound healing and
      vascular regeneration within the graft union zone. Incomplete and convoluted
      vascular connections impede the vital upward and downward whole plant transfer
      routes. Long-distance protein, mRNA and small RNA graft-transmissible signals
      currently emerge as novel mechanisms which regulate nutritional and developmental
      root/top relations and may play a pivotal role in grafting physiology. Grafting
      also has significant pathogenic projections. On one hand, stock to scion
      mechanical contact enables the spread of diseases, even without a complete graft
      union. But, on the other hand, grafting onto resistant rootstocks serves as a
      principal tool in the management of fruit tree plagues and vegetable soil-borne
      diseases. The 'graft hybrid' historic controversy has not yet been resolved.
      Recent evidence suggests that epigenetic modification of DNA-methylation patterns
      may account for certain graft-transformation phenomena. Root grafting is a wide
      spread natural phenomenon; both intraspecific and interspecific root grafts have
      been recorded. Root grafts have an evolutionary role in the survival of storm-hit
      forest stands as well as in the spread of devastating diseases. A more
      fundamental evolutionary role is hinted by recent findings that demonstrate
      plastid and nuclear genome transfer between distinct Nicotiana species in the
      graft union zone, within a tissue culture system. This has led to the formation
      of alloploid cells that, under laboratory conditions, gave rise to a novel,
      alloploid Nicotiana species, indicating that natural grafts may play a role in
      plant speciation, under certain circumstances. 

PMID- 25566299
TI  - MeioBase: a comprehensive database for meiosis.
AB  - Meiosis is a special type of cell division process necessary for the sexual
      reproduction of all eukaryotes. The ever expanding meiosis research calls for an
      effective and specialized database that is not readily available yet. To fill
      this gap, we have developed a knowledge database MeioBase
      (http://meiosis.ibcas.ac.cn), which is comprised of two core parts, Resources and
      Tools. In the Resources part, a wealth of meiosis data collected by curation and
      manual review from published literatures and biological databases are integrated
      and organized into various sections, such as Cytology, Pathway, Species,
      Interaction, and Expression. In the Tools part, some useful tools have been
      integrated into MeioBase, such as Search, Download, Blast, Comparison, My
      Favorites, Submission, and Advice. With a simplified and efficient web interface,
      users are able to search against the database with gene model IDs or keywords,
      and batch download the data for local investigation. We believe that MeioBase can
      greatly facilitate the researches related to meiosis. 

PMID- 25566301
TI  - Do pathogen effectors play peek-a-boo?

PMID- 25566300
TI  - The expression and roles of parent-of-origin genes in early embryogenesis of
      angiosperms.
AB  - Uniparental transcripts during embryogenesis may arise due to gamete delivery
      during fertilization or genomic imprinting. Such transcripts have been found in a
      number of plant species and appear critical for the early development of embryo
      or endosperm in seeds. Although the regulatory expression mechanism and function
      of these genes in embryogenesis require further elucidation, recent studies
      suggest stage-specific and highly dynamic features that might be essential for
      critical developmental events such as zygotic division and cell fate
      determination during embryogenesis. Here, we summarize the current work in this
      field and discuss future research directions. 

PMID- 25566302
TI  - Vernalization and the chilling requirement to exit bud dormancy: shared or
      separate regulation?
AB  - Similarities have long been recognized between vernalization, the prolonged
      exposure to cold temperatures that promotes the floral transition in many plants,
      and the chilling requirement to release bud dormancy in woody plants of temperate
      climates. In both cases the extended chilling period occurring during winter is
      used to coordinate developmental events to the appropriate seasonal time.
      However, whether or not these processes share common regulatory components and
      molecular mechanisms remain largely unknown. Both gene function and association
      genetics studies in Populus are beginning to answer this question. In Populus,
      studies have revealed that orthologs of the antagonistic flowering time genes FT
      and CEN/TFL1 might have central roles in both processes. We review Populus
      seasonal shoot development related to dormancy release and the floral transition
      and evidence for FT/TFL1-mediated regulation of these processes to consider the
      question of regulatory overlap. In addition, we discuss the potential for and
      challenges to integrating functional and population genomics studies to uncover
      the regulatory mechanisms underpinning these processes in woody plant systems. 

PMID- 25566304
TI  - Interactions of Xanthomonas type-III effector proteins with the plant ubiquitin
      and ubiquitin-like pathways.
AB  - In eukaryotes, regulated protein turnover is required during many cellular
      processes, including defense against pathogens. Ubiquitination and degradation of
      ubiquitinated proteins via the ubiquitin-proteasome system (UPS) is the main
      pathway for the turnover of intracellular proteins in eukaryotes. The extensive
      utilization of the UPS in host cells makes it an ideal pivot for the manipulation
      of cellular processes by pathogens. Like many other Gram-negative bacteria,
      Xanthomonas species secrete a suite of type-III effector proteins (T3Es) into
      their host cells to promote virulence. Some of these T3Es exploit the plant UPS
      to interfere with immunity. This review summarizes T3E examples from the genus
      Xanthomonas with a proven or suggested interaction with the host UPS or UPS-like
      systems and also discusses the apparent paradox that arises from the presence of
      T3Es that inhibit the UPS in general while others rely on its activity for their
      function. 

PMID- 25566305
TI  - Characterization of in vitro haploid and doubled haploid Chrysanthemum morifolium
      plants via unfertilized ovule culture for phenotypical traits and DNA methylation
      pattern.
AB  - Chrysanthemum is one of important ornamental species in the world. Its highly
      heterozygous state complicates molecular analysis, so it is of interest to derive
      haploid forms. A total of 2579 non-fertilized chrysanthemum ovules pollinated by
      Argyranthemum frutescens were cultured in vitro to isolate haploid progeny. One
      single regenerant emerged from each of three of the 105 calli produced.
      Chromosome counts and microsatellite fingerprinting showed that only one of the
      regenerants was a true haploid. Nine doubled haploid derivatives were
      subsequently generated by colchicine treatment of 80 in vitro cultured haploid
      nodal segments. Morphological screening showed that the haploid plant was shorter
      than the doubled haploids, and developed smaller leaves, flowers, and stomata. An
      in vitro pollen germination test showed that few of the haploid's pollen were
      able to germinate and those which did so were abnormal. Both the haploid and the
      doubled haploids produced yellow flowers, whereas those of the maternal parental
      cultivar were mauve. Methylation-sensitive amplification polymorphism (MSAP)
      profiling was further used to detect alterations in cytosine methylation caused
      by the haploidization and/or the chromosome doubling processes. While 52.2% of
      the resulting amplified fragments were cytosine methylated in the maternal
      parent's genome, the corresponding proportions for the haploid's and doubled
      haploids' genomes were, respectively, 47.0 and 51.7%, demonstrating a reduction
      in global cytosine methylation caused by haploidization and a partial recovery
      following chromosome doubling. 

PMID- 25566303
TI  - Plasma membrane protein trafficking in plant-microbe interactions: a plant cell
      point of view.
AB  - In order to ensure their physiological and cellular functions, plasma membrane
      (PM) proteins must be properly conveyed from their site of synthesis, i.e., the
      endoplasmic reticulum, to their final destination, the PM, through the secretory
      pathway. PM protein homeostasis also relies on recycling and/or degradation, two
      processes that are initiated by endocytosis. Vesicular membrane trafficking
      events to and from the PM have been shown to be altered when plant cells are
      exposed to mutualistic or pathogenic microbes. In this review, we will describe
      the fine-tune regulation of such alterations, and their consequence in PM protein
      activity. We will consider the formation of intracellular perimicrobial
      compartments, the PM protein trafficking machinery of the host, and the delivery
      or retrieval of signaling and transport proteins such as pattern-recognition
      receptors, producers of reactive oxygen species, and sugar transporters. 

PMID- 25566306
TI  - Subtilisin-like proteases in plant-pathogen recognition and immune priming: a
      perspective.
AB  - Subtilisin-like proteases (subtilases) are serine proteases that fulfill highly
      specific functions in plant development and signaling cascades. Over the last
      decades, it has been shown that several subtilases are specifically induced
      following pathogen infection and very recently an Arabidopsis subtilase (SBT3.3)
      was hypothesized to function as a receptor located in the plasma membrane
      activating downstream immune signaling processes. Despite their prevalence and
      potential relevance in the regulation of plant defense mechanisms and crop
      improvement, our current understanding of subtilase function is still very
      limited. In this perspective article, we overview the current status and
      highlight the involvement of subtilases in pathogen recognition and immune
      priming. 

PMID- 25566307
TI  - Functional imaging in living plants-cell biology meets physiology.

PMID- 25566308
TI  - Genome-wide identification of non-coding RNAs interacted with microRNAs in
      soybean.
AB  - A wide range of RNA species interacting with microRNAs (miRNAs) form a complex
      gene regulation network and play vital roles in diverse biological processes. In
      this study, we performed a genome-wide identification of endogenous target mimics
      (eTMs) for miRNAs and phased-siRNA-producing loci (PHAS) in soybean with a focus
      on those involved in lipid metabolism. The results showed that a large number of
      eTMs and PHAS genes could be found in soybean. Additionally, we found that lipid
      metabolism related genes were potentially regulated by 28 miRNAs, and nine of
      them were potentially further regulated by a number of eTMs with expression
      evidence. Thirty-three miRNAs were found to trigger production of phasiRNAs from
      49 PHAS genes, which were able to target lipid metabolism related genes.
      Degradome data supported miRNA- and/or phasiRNA-mediated cleavage of genes
      involved in lipid metabolism. Most eTMs for miRNAs involved in lipid metabolism
      and phasiRNAs targeting lipid metabolism related genes showed a tissue-specific
      expression pattern. Our bioinformatical evidences suggested that lipid metabolism
      in soybean is potentially regulated by a complex non-coding network, including
      miRNAs, eTMs, and phasiRNAs, and the results extended our knowledge on functions
      of non-coding RNAs. 

PMID- 25566309
TI  - Protein-protein interaction and gene co-expression maps of ARFs and Aux/IAAs in
      Arabidopsis.
AB  - The phytohormone auxin regulates nearly all aspects of plant growth and
      development. Based on the current model in Arabidopsis thaliana, Auxin/indole-3
      acetic acid (Aux/IAA) proteins repress auxin-inducible genes by inhibiting auxin
      response transcription factors (ARFs). Experimental evidence suggests that
      heterodimerization between Aux/IAA and ARF proteins are related to their unique
      biological functions. The objective of this study was to generate the Aux/IAA-ARF
      protein-protein interaction map using full length sequences and locate the
      interacting protein pairs to specific gene co-expression networks in order to
      define tissue-specific responses of the Aux/IAA-ARF interactome. Pairwise
      interactions between 19 ARFs and 29 Aux/IAAs resulted in the identification of
      213 specific interactions of which 79 interactions were previously unknown. The
      incorporation of co-expression profiles with protein-protein interaction data
      revealed a strong correlation of gene co-expression for 70% of the ARF-Aux/IAA
      interacting pairs in at least one tissue/organ, indicative of the biological
      significance of these interactions. Importantly, ARF4-8 and 19, which were found
      to interact with almost all Aux-Aux/IAA showed broad co-expression relationships
      with Aux/IAA genes, thus, formed the central hubs of the co-expression network.
      Our analyses provide new insights into the biological significance of ARF-Aux/IAA
      associations in the morphogenesis and development of various plant tissues and
      organs. 

PMID- 25566310
TI  - A simple, rapid, and reliable protocol to localize hydrogen peroxide in large
      plant organs by DAB-mediated tissue printing.
AB  - Hydrogen peroxide (H2O2) is a major reactive oxygen species (ROS) and plays
      diverse roles in plant development and stress responses. However, its
      localization in large and thick plant organs (e.g., stem, roots, and fruits),
      other than leaves, has proven to be challenging due to the difficulties for the
      commonly used H2O2-specific chemicals, such as 3,3'-diaminobenzidine (DAB),
      cerium chloride (CeCl3), and 2',7'-dichlorofluorescin diacetate (H2DCF-DA), to
      penetrate those organs. Theoretically, the reaction of endogenous H2O2 with these
      chemicals could be facilitated by using thin organ sections. However, the rapid
      production of wound-induced H2O2 associated with this procedure inevitably
      disturbs the original distribution of H2O2 in vivo. Here, by employing tomato
      seedling stems and fruits as testing materials, we report a novel, simple, and
      rapid protocol to localize H2O2 in those organs using DAB-mediated tissue
      printing. The rapidity of the protocol (within 15 s) completely avoided the
      interference of wound-induced H2O2 during experimentation. Moreover, the H2O2
      signal on the printing was stable for at least 1 h with no or little background
      produced. We conclude that DAB-mediated tissue printing developed here provide a
      new feasible and reliable method to localize H2O2 in large plant organs, hence
      should have broad applications in studying ROS biology. 

PMID- 25566311
TI  - Biophysical and biochemical constraints imposed by salt stress: learning from
      halophytes.
AB  - Soil salinization is one of the most important factors impacting plant
      productivity. About 3.6 billion of the world's 5.2 billion ha of agricultural dry
      land, have already suffered erosion, degradation, and salinization. Halophytes
      are typically considered as plants able to complete their life cycle in
      environments where the salt concentration is above 200 mM NaCl. Salinity
      adjustment is a complex phenomenon but essential mechanism to overcome salt
      stress, with both biophysical and biochemical implications. At this level,
      halophytes evolved in several directions, adopting different strategies.
      Otherwise, the lack of adaptation to a salt environment would negatively affect
      their electron transduction pathways and the entire energetic metabolism, the
      foundation of every plant photosynthesis and biomass production. The maintenance
      of ionic homeostasis is in the basis of all cellular counteractive measures, in
      particular in terms of redox potential and energy transduction. In the present
      work the biophysical mechanisms underlying energy capture and transduction in
      halophytes are discussed alongside with their relation with biochemical
      counteractive mechanisms, integrating data from photosynthetic light harvesting
      complexes, electron transport chains to the quinone pools, carbon fixation, and
      energy dissipation metabolism. 

PMID- 25566312
TI  - ATR-FTIR spectroscopy reveals involvement of lipids and proteins of intact pea
      pollen grains to heat stress tolerance.
AB  - With climate change, pea will be more frequently subjected to heat stress in semi
      arid regions like Saskatchewan during flowering. The pollen germination
      percentage of two pea cultivars was reduced by heat stress (36 degrees C) with an
      important decrease in cultivar 'CDC Golden' compared to 'CDC Sage.' Lipids,
      protein and other pollen coat compositions of whole intact pollen grains of both
      pea cultivars were investigated using mid infrared (mid-IR) attenuated total
      reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy. Curve fitting
      of ATR absorbance spectra in the protein region enabled estimation and comparison
      of different protein secondary structures between the two cultivars. CDC Sage had
      relatively greater amounts of alpha-helical structures (48.6-43.6%; band at 1654
      cm(-1)) and smaller amounts of beta-sheets (41.3-46%) than CDC Golden. The CDC
      Golden had higher amounts of beta-sheets (46.3-51.7%) compared to alpha-helical
      structures (35.3-36.2%). Further, heat stress resulted in prominent changes in
      the symmetrical and asymmetrical CH2 bands from lipid acyl chain, ester carbonyl
      band, and carbohydrate region. The intensity of asymmetric and symmetric CH2
      vibration of heat stressed CDC Golden was reduced considerably in comparison to
      the control and the decrease was higher compared to CDC Sage. In addition, CDC
      Golden showed an increase in intensity at the oxidative band of 3015 cm(-1).
      These results reveal that the whole pollen grains of both pea cultivars responded
      differently to heat stress. The tolerance of CDC Sage to heat stress (expressed
      as pollen germination percentage) may be due to its protein richness with alpha
      helical structures which would protect against the destructive effects of
      dehydration due to heat stress. The low pollen germination percentage of CDC
      Golden after heat stress may be also due to its sensitivity to lipid changes due
      to heat stress. 

PMID- 25566313
TI  - The role of ROS signaling in cross-tolerance: from model to crop.
AB  - Reactive oxygen species (ROS) are key signaling molecules produced in response to
      biotic and abiotic stresses that trigger a variety of plant defense responses.
      Cross-tolerance, the enhanced ability of a plant to tolerate multiple stresses,
      has been suggested to result partly from overlap between ROS signaling
      mechanisms. Cross-tolerance can manifest itself both as a positive genetic
      correlation between tolerance to different stresses (inherent cross-tolerance),
      and as the priming of systemic plant tolerance through previous exposure to
      another type of stress (induced cross-tolerance). Research in model organisms
      suggests that cross-tolerance could be used to benefit the agronomy and breeding
      of crop plants. However, research under field conditions has been scarce and
      critical issues including the timing, duration, and intensity of a stressor, as
      well as its interactions with other biotic and abiotic factors, remain to be
      addressed. Potential applications include the use of chemical stressors to screen
      for stress-resistant genotypes in breeding programs and the agronomic use of
      chemical inducers of plant defense for plant protection. Success of these
      applications will rely on improving our understanding of how ROS signals travel
      systemically and persist over time, and of how genetic correlations between
      resistance to ROS, biotic, and abiotic stresses are shaped by cooperative and
      antagonistic interactions within the underlying signaling pathways. 

PMID- 25566314
TI  - Imputation and quality control steps for combining multiple genome-wide datasets.
AB  - The electronic MEdical Records and GEnomics (eMERGE) network brings together DNA
      biobanks linked to electronic health records (EHRs) from multiple institutions.
      Approximately 51,000 DNA samples from distinct individuals have been genotyped
      using genome-wide SNP arrays across the nine sites of the network. The eMERGE
      Coordinating Center and the Genomics Workgroup developed a pipeline to impute and
      merge genomic data across the different SNP arrays to maximize sample size and
      power to detect associations with a variety of clinical endpoints. The 1000
      Genomes cosmopolitan reference panel was used for imputation. Imputation results
      were evaluated using the following metrics: accuracy of imputation, allelic R (2)
      (estimated correlation between the imputed and true genotypes), and the
      relationship between allelic R (2) and minor allele frequency. Computation time
      and memory resources required by two different software packages (BEAGLE and
      IMPUTE2) were also evaluated. A number of challenges were encountered due to the
      complexity of using two different imputation software packages, multiple
      ancestral populations, and many different genotyping platforms. We present
      lessons learned and describe the pipeline implemented here to impute and merge
      genomic data sets. The eMERGE imputed dataset will serve as a valuable resource
      for discovery, leveraging the clinical data that can be mined from the EHR. 

PMID- 25566317
TI  - A lesson from the ice bucket challenge: using social networks to publicize
      science.

PMID- 25566315
TI  - Analysis of two domains with novel RNA-processing activities throws light on the
      complex evolution of ribosomal RNA biogenesis.
AB  - Ribosomal biogenesis has been extensively investigated, especially to identify
      the elusive nucleases and cofactors involved in the complex rRNA processing
      events in eukaryotes. Large-scale screens in yeast identified two biochemically
      uncharacterized proteins, TSR3 and TSR4, as being key players required for rRNA
      maturation. Using multiple computational approaches we identify the conserved
      domains comprising these proteins and establish sequence and structural features
      providing novel insights regarding their roles. TSR3 is unified with the DTW
      domain into a novel superfamily of predicted enzymatic domains, with the balance
      of the available evidence pointing toward an RNase role with the archaeo
      eukaryotic TSR3 proteins processing rRNA and the bacterial versions potentially
      processing tRNA. TSR4, its other eukaryotic homologs PDCD2/rp-8, PDCD2L, Zfrp8,
      and trus, the predominantly bacterial DUF1963 proteins, and other uncharacterized
      proteins are unified into a new domain superfamily, which arose from an ancient
      duplication event of a strand-swapped, dimer-forming all-beta unit. We identify
      conserved features mediating protein-protein interactions (PPIs) and propose a
      potential chaperone-like function. While contextual evidence supports a conserved
      role in ribosome biogenesis for the eukaryotic TSR4-related proteins, there is no
      evidence for such a role for the bacterial versions. Whereas TSR3-related
      proteins can be traced to the last universal common ancestor (LUCA) with a well
      supported archaeo-eukaryotic branch, TSR4-related proteins of eukaryotes are
      derived from within the bacterial radiation of this superfamily, with archaea
      entirely lacking them. This provides evidence for "systems admixture," which
      followed the early endosymbiotic event, playing a key role in the emergence of
      the uniquely eukaryotic ribosome biogenesis process. 

PMID- 25566316
TI  - Molecular signatures and phylogenomic analysis of the genus Burkholderia:
      proposal for division of this genus into the emended genus Burkholderia
      containing pathogenic organisms and a new genus Paraburkholderia gen. nov.
      harboring environmental species.
AB  - The genus Burkholderia contains large number of diverse species which include
      many clinically important organisms, phytopathogens, as well as environmental
      species. However, currently, there is a paucity of biochemical or molecular
      characteristics which can reliably distinguish different groups of Burkholderia
      species. We report here the results of detailed phylogenetic and comparative
      genomic analyses of 45 sequenced species of the genus Burkholderia. In
      phylogenetic trees based upon concatenated sequences for 21 conserved proteins as
      well as 16S rRNA gene sequence based trees, members of the genus Burkholderia
      grouped into two major clades. Within these main clades a number of smaller
      clades including those corresponding to the clinically important Burkholderia
      cepacia complex (BCC) and the Burkholderia pseudomallei groups were also clearly
      distinguished. Our comparative analysis of protein sequences from Burkholderia
      spp. has identified 42 highly specific molecular markers in the form of conserved
      sequence indels (CSIs) that are uniquely found in a number of well-defined groups
      of Burkholderia spp. Six of these CSIs are specific for a group of Burkholderia
      spp. (referred to as Clade I in this work) which contains all clinically relevant
      members of the genus (viz. the BCC and the B. pseudomallei group) as well as the
      phytopathogenic Burkholderia spp. The second main clade (Clade II), which is
      composed of environmental Burkholderia species, is also distinguished by 2
      identified CSIs that are specific for this group. Additionally, our work has also
      identified multiple CSIs that serve to clearly demarcate a number of smaller
      groups of Burkholderia spp. including 3 CSIs that are specific for the B. cepacia
      complex, 4 CSIs that are uniquely found in the B. pseudomallei group, 5 CSIs that
      are specific for the phytopathogenic Burkholderia spp. and 22 other CSI that
      distinguish two groups within Clade II. The described molecular markers provide
      highly specific means for the demarcation of different groups of Burkholderia
      spp. and they also offer novel and useful targets for the development of
      diagnostic assays for the clinically important members of the BCC or the
      pseudomallei groups. Based upon the results of phylogenetic analyses, the
      identified CSIs and the pathogenicity profile of Burkholderia species, we are
      proposing a division of the genus Burkholderia into two genera. In this new
      proposal, the emended genus Burkholderia will correspond to the Clade I and it
      will contain only the clinically relevant and phytopathogenic Burkholderia
      species. All other Burkholderia spp., which are primarily environmental, will be
      transferred to a new genus Paraburkholderia gen. nov. 

PMID- 25566318
TI  - Pleiotropy constrains the evolution of protein but not regulatory sequences in a
      transcription regulatory network influencing complex social behaviors.
AB  - It is increasingly apparent that genes and networks that influence complex
      behavior are evolutionary conserved, which is paradoxical considering that
      behavior is labile over evolutionary timescales. How does adaptive change in
      behavior arise if behavior is controlled by conserved, pleiotropic, and likely
      evolutionary constrained genes? Pleiotropy and connectedness are known to
      constrain the general rate of protein evolution, prompting some to suggest that
      the evolution of complex traits, including behavior, is fuelled by regulatory
      sequence evolution. However, we seldom have data on the strength of selection on
      mutations in coding and regulatory sequences, and this hinders our ability to
      study how pleiotropy influences coding and regulatory sequence evolution. Here we
      use population genomics to estimate the strength of selection on coding and
      regulatory mutations for a transcriptional regulatory network that influences
      complex behavior of honey bees. We found that replacement mutations in highly
      connected transcription factors and target genes experience significantly
      stronger negative selection relative to weakly connected transcription factors
      and targets. Adaptively evolving proteins were significantly more likely to
      reside at the periphery of the regulatory network, while proteins with signs of
      negative selection were near the core of the network. Interestingly,
      connectedness and network structure had minimal influence on the strength of
      selection on putative regulatory sequences for both transcription factors and
      their targets. Our study indicates that adaptive evolution of complex behavior
      can arise because of positive selection on protein-coding mutations in peripheral
      genes, and on regulatory sequence mutations in both transcription factors and
      their targets throughout the network. 

PMID- 25566319
TI  - Parentage assignment with genomic markers: a major advance for understanding and
      exploiting genetic variation of quantitative traits in farmed aquatic animals.
AB  - Since the middle of the 1990s, parentage assignment using microsatellite markers
      has been introduced as a tool in aquaculture breeding. It now allows close to
      100% assignment success, and offered new ways to develop aquaculture breeding
      using mixed family designs in commercial conditions. Its main achievements are
      the knowledge and control of family representation and inbreeding, especially in
      mass spawning species, above all the capacity to estimate reliable genetic
      parameters in any species and rearing system with no prior investment in
      structures, and the development of new breeding programs in many species.
      Parentage assignment should not be seen as a way to replace physical tagging, but
      as a new way to conceive breeding programs, which have to be optimized with its
      specific constraints, one of the most important being to well define the number
      of individuals to genotype to limit costs, maximize genetic gain while minimizing
      inbreeding. The recent possible shift to (for the moment) more costly single
      nucleotide polymorphism markers should benefit from future developments in
      genomics and marker-assisted selection to combine parentage assignment and
      indirect prediction of breeding values. 

PMID- 25566320
TI  - The establishment of Central American migratory corridors and the biogeographic
      origins of seasonally dry tropical forests in Mexico.
AB  - Biogeography and community ecology can mutually illuminate the formation of a
      regional species pool or biome. Here, we apply phylogenetic methods to a large
      and diverse plant clade, Malpighiaceae, to characterize the formation of its
      species pool in Mexico, and its occupancy of the seasonally dry tropical forest
      (SDTF) biome that occurs there. We find that the ~162 species of Mexican
      Malpighiaceae represent ~33 dispersals from South America beginning in the Eocene
      and continuing until the Pliocene (~46.4-3.8 Myr). Furthermore, dispersal rates
      between South America and Mexico show a significant six-fold increase during the
      mid-Miocene (~23.9 Myr). We hypothesize that this increase marked the
      availability of Central America as an important corridor for Neotropical plant
      migration. We additionally demonstrate that this high rate of dispersal
      contributed substantially more to the phylogenetic diversity of Malpighiaceae in
      Mexico than in situ diversification. Finally, we show that most lineages arrived
      in Mexico pre-adapted with regard to one key SDTF trait, total annual
      precipitation. In contrast, these lineages adapted to a second key trait,
      precipitation seasonality, in situ as mountain building in the region gave rise
      to the abiotic parameters of extant SDTF. The timing of this in situ adaptation
      to seasonal precipitation suggests that SDTF likely originated its modern
      characteristics by the late Oligocene, but was geographically more restricted
      until its expansion in the mid-Miocene. These results highlight the complex
      interplay of dispersal, adaptation, and in situ diversification in the formation
      of tropical biomes. Our results additionally demonstrate that these processes are
      not static, and their relevance can change markedly over evolutionary time. This
      has important implications for understanding the origin of SDTF in Mexico, but
      also for understanding the temporal and spatial origin of biomes and regional
      species pools more broadly. 

PMID- 25566321
TI  - Embryo transfers between C57BL/6J and DBA/2J mice: Examination of a maternal
      effect on ethanol teratogenesis.
AB  - Genetic factors influence fetal alcohol spectrum disorders (FASDs) in both humans
      and animals. Experiments using inbred and selectively bred mouse stocks that
      controlled for (1) ethanol dose, (2) maternal and fetal blood ethanol levels, and
      (3) fetal developmental exposure stage, show genotype can affect teratogenic
      outcome. Other experiments distinguish the teratogenic effects mediated by
      maternal genotype from those mediated by fetal genotype. One technique to
      distinguish maternal versus fetal genotype effect is to utilize embryo transfers.
      This study is the first to examine ethanol teratogenesis - fetal weight deficits
      and mortality, and digit, kidney, and vertebral malformations - in C57BL/6J (B6)
      and DBA/2J (D2) fetuses that were transferred as blastocysts into B6 and D2 dams.
      We hypothesized that, following maternal alcohol exposure, B6 and D2 fetuses
      gestating within B6 mothers, as compared to D2 mothers, will exhibit a higher
      frequency of malformations. On day 9 of pregnancy, females were intubated (IG)
      with either 5.8 g/kg ethanol (E) or maltose-dextrin (MD). Other females were
      mated within strain and treated with either ethanol or maltose, or were not
      exposed to either treatment. Implantation rates were affected by genotype.
      Results show more B6 embryos implanted into D2 females than B6 females (p < 0.05;
      47% vs. 23%, respectively). There was no difference in the percentage of D2
      embryos implanting into B6 and D2 females (14 and 16%, respectfully). Litter
      mortality averaged 24% across all experimental groups. Overall, in utero ethanol
      exposure reduced mean litter weight compared to maltose treatment (E = 1.01 g; MD
      = 1.19 g; p < 0.05); but maltose exposed litters with transferred embryos weighed
      more than similarly treated natural litters (1.30 g vs. 1.11 g; p < 0.05).
      Approximately 50% of all ethanol exposed B6 fetuses exhibited some malformation
      (digit, vertebral, and/or kidney) regardless of whether they were transferred
      into a B6 or D2 female, or were naturally conceived. This suggests the D2
      maternal uterine environment did not offer any protection against ethanol
      teratogenesis for B6 fetuses. One of the questions remaining is the how the B6
      uterine environment affects D2 teratogenesis. No definitive conclusions can be
      drawn because too few viable D2 litters were produced. 

PMID- 25566324
TI  - Citizens' preferences for the conservation of agricultural genetic resources.
AB  - Evaluation of conservation policies for agricultural genetic resources (AgGR)
      requires information on the use and non-use values of plant varieties and animal
      breeds, as well as on the preferences for in situ and ex situ conservation. We
      conducted a choice experiment to estimate citizens' willingness to pay (WTP) for
      AgGR conservation programmes in Finland, and used a latent class model to
      identify heterogeneity in preferences among respondent groups. The findings
      indicate that citizens have a high interest in the conservation of native breeds
      and varieties, but also reveal the presence of preference heterogeneity. Five
      respondent groups could be identified based on latent class modeling: one
      implying lexicographic preferences, two with reasoned choices, one indicating
      uncertain support and one with a preference for the current status of
      conservation. The results emphasize the importance of in situ conservation of
      native cattle breeds and plant varieties in developing conservation policies. 

PMID- 25566323
TI  - TM6SF2 and MAC30, new enzyme homologs in sterol metabolism and common metabolic
      disease.
AB  - Carriers of the Glu167Lys coding variant in the TM6SF2 gene have recently been
      identified as being more susceptible to non-alcoholic fatty liver disease
      (NAFLD), yet exhibit lower levels of circulating lipids and hence are protected
      against cardiovascular disease. Despite the physiological importance of these
      observations, the molecular function of TM6SF2 remains unknown, and no sequence
      similarity with functionally characterized proteins has been identified. In order
      to trace its evolutionary history and to identify functional domains, we embarked
      on a computational protein sequence analysis of TM6SF2. We identified a new
      domain, the EXPERA domain, which is conserved among TM6SF, MAC30/TMEM97 and EBP
      (D8, D7 sterol isomerase) protein families. EBP mutations are the cause of
      chondrodysplasia punctata 2 X-linked dominant (CDPX2), also known as Conradi
      Hunermann-Happle syndrome, a defective cholesterol biosynthesis disorder. Our
      analysis of evolutionary conservation among EXPERA domain-containing families and
      the previously suggested catalytic mechanism for the EBP enzyme, indicate that
      TM6SF and MAC30/TMEM97 families are both highly likely to possess, as for the EBP
      family, catalytic activity as sterol isomerases. This unexpected prediction of
      enzymatic functions for TM6SF and MAC30/TMEM97 is important because it now
      permits detailed experiments to investigate the function of these key proteins in
      various human pathologies, from cardiovascular disease to cancer. 

PMID- 25566325
TI  - Genomic adaptation of admixed dairy cattle in East Africa.
AB  - Dairy cattle in East Africa imported from the U.S. and Europe have been adapted
      to new environments. In small local farms, cattle have generally been maintained
      by crossbreeding that could increase survivability under a severe environment.
      Eventually, genomic ancestry of a specific breed will be nearly fixed in genomic
      regions of local breeds or crossbreds when it is advantageous for survival or
      production in harsh environments. To examine this situation, 25 Friesians and 162
      local cattle produced by crossbreeding of dairy breeds in Kenya were sampled and
      genotyped using 50K SNPs. Using principal component analysis (PCA), the admixed
      local cattle were found to consist of several imported breeds, including
      Guernsey, Norwegian Red, and Holstein. To infer the influence of parental breeds
      on genomic regions, local ancestry mapping was performed based on the similarity
      of haplotypes. As a consequence, it appears that no genomic region has been under
      the complete influence of a specific parental breed. Nonetheless, the ancestry of
      Holstein-Friesians was substantial in most genomic regions (>80%). Furthermore,
      we examined the frequency of the most common haplotypes from parental breeds that
      have changed substantially in Kenyan crossbreds during admixture. The frequency
      of these haplotypes from parental breeds, which were likely to be selected in
      temperate regions, has deviated considerably from expected frequency in 11
      genomic regions. Additionally, extended haplotype homozygosity (EHH) based
      methods were applied to identify the regions responding to recent selection in
      crossbreds, called candidate regions, resulting in seven regions that appeared to
      be affected by Holstein-Friesians. However, some signatures of selection were
      less dependent on Holsteins-Friesians, suggesting evidence of adaptation in East
      Africa. The analysis of local ancestry is a useful approach to understand the
      detailed genomic structure and may reveal regions of the genome required for
      specialized adaptation when combined with methods for searching for the recent
      changes of haplotype frequency in an admixed population. 

PMID- 25566322
TI  - Potential of epigenetic therapies in non-cancerous conditions.
AB  - There has been an explosion of knowledge in the epigenetics field in the past 20
      years. The first epigenetic therapies have arrived in the clinic for cancer
      treatments. In contrast, much of the promise of epigenetic therapies for non
      cancerous conditions remains in the laboratories. The current review will focus
      on the recent progress that has been made in understanding the pathogenic role of
      epigenetics in immune and inflammatory conditions, and how the knowledge may
      provide much needed new therapeutic targets for many autoimmune diseases. Dietary
      factors are increasingly recognized as potential modifiers of epigenetic marks
      that can influence health and diseases across generations. The current
      epigenomics revolution will almost certainly complement the explosion of personal
      genetics medicine to help guide treatment decisions and disease risk
      stratification. 

PMID- 25566326
TI  - Schistosome and liver fluke derived catechol-estrogens and helminth associated
      cancers.
AB  - Infection with helminth parasites remains a persistent public health problem in
      developing countries. Three of these pathogens, the liver flukes Clonorchis
      sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are
      of particular concern due to their classification as Group 1 carcinogens:
      infection with these worms is carcinogenic. Using liquid chromatography-mass
      spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g.,
      oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA
      adducts, apparently of parasite origin, in developmental stages including eggs of
      S. haematobium, in urine of people with urogenital schistosomiasis, and in the
      adult stage of O. viverrini. Since these kinds of sterol derivatives are
      metabolized to active quinones that can modify DNA, which in other contexts can
      lead to breast and other cancers, helminth parasite associated sterols might
      induce tumor-like phenotypes in the target cells susceptible to helminth parasite
      associated cancers, i.e., urothelial cells of the bladder in the case of
      urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the
      case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced
      cancers originate from parasite estrogen-host epithelial/urothelial cell
      chromosomal DNA adducts, and here we review recent findings that support this
      conjecture. 

PMID- 25566328
TI  - Aging-modulating treatments: from reductionism to a system-oriented perspective.

PMID- 25566327
TI  - Developmental regulation of ecdysone receptor (EcR) and EcR-controlled gene
      expression during pharate-adult development of honeybees (Apis mellifera).
AB  - Major developmental transitions in multicellular organisms are driven by steroid
      hormones. In insects, these, together with juvenile hormone (JH), control
      development, metamorphosis, reproduction and aging, and are also suggested to
      play an important role in caste differentiation of social insects. Here, we aimed
      to determine how EcR transcription and ecdysteroid titers are related during
      honeybee postembryonic development and what may actually be the role of EcR in
      caste development of this social insect. In addition, we expected that knocking
      down EcR gene expression would give us information on the participation of the
      respective protein in regulating downstream targets of EcR. We found that in Apis
      mellifera females, EcR-A is the predominantly expressed variant in postembryonic
      development, while EcR-B transcript levels are higher in embryos, indicating an
      early developmental switch in EcR function. During larval and pupal stages, EcR-B
      expression levels are very low, while EcR-A transcripts are more variable and
      abundant in workers compared to queens. Strikingly, these transcript levels are
      opposite to the ecdysteroid titer profile. 20-hydroxyecdysone (20E) application
      experiments revealed that low 20E levels induce EcR expression during
      development, whereas high ecdysteroid titers seem to be repressive. By means of
      RNAi-mediated knockdown (KD) of both EcR transcript variants we detected the
      differential expression of 234 poly-A(+) transcripts encoding genes such as CYPs,
      MRJPs and certain hormone response genes (Kr-h1 and ftz-f1). EcR-KD also promoted
      the differential expression of 70 miRNAs, including highly conserved ones (e.g.,
      miR-133 and miR-375), as well honeybee-specific ones (e.g., miR-3745 and miR
      3761). Our results put in evidence a broad spectrum of EcR-controlled gene
      expression during postembryonic development of honeybees, revealing new facets of
      EcR biology in this social insect. 

PMID- 25566329
TI  - p53 binding to human genome: crowd control navigation in chromatin context.
AB  - p53 is the most studied human protein because of its role in maintaining genomic
      stability. Binding to genomic targets is essential for transcription-dependent
      p53 tumor suppression, but how p53 selects targets remains unclear. Here, the
      impact of chromatin context on p53 genome-wide binding and targets selection is
      discussed. It is proposed that p53 genomic binding serves not only to regulate
      transcription, but to sense epigenomic changes threatening the genomic integrity.
      The problem of p53 navigating the human genome is discussed with respect to the
      degenerate p53 binding motif. This discussion relates to the fundamental problem
      of DNA binding factors navigating large genomes in search for cognate binding
      sites. 

PMID- 25566331
TI  - Giant keratocystic odontogenic tumor of the mandible - a case report.
AB  - BACKGROUND: The keratocystic odontogenic tumor (KCOT) is a relatively rare,
      benign neoplasm which develops in the maxilla or mandible, arising from the
      dental lamina or basal cells of the oral epithelium. It is often found
      incidentally and brings about late symptoms as it does not cause bone distension
      for a long time. CASE REPORT: The presented case is of a young woman with a giant
      keratocystic odontogenic tumor of the mandible. CONCLUSIONS: Despite its rare
      occurrence, it must be taken into consideration in radiological and clinical
      diagnostics. Due to the frequent recurrence of KCOT, patients are recommended to
      be kept under long-term and close radiological supervision.

PMID- 25566332
TI  - Omalizumab vs. placebo in the management of chronic idiopathic urticaria: a
      systematic review.
AB  - OBJECTIVES: To examine the evidence derived from randomized controlled clinical
      trials on the efficacy and safety of omalizumab compared to placebo in
      controlling symptoms of chronic idiopathic urticaria/chronic spontaneous
      urticaria (CIU/CSU). DATA SOURCE: The electronic databases PubMed, Medline,
      EMBASE, Biomed Central, The Cochrane Central Register of Controlled Trials
      (CENTRAL), Wiley, OVID, and HighwirePress were reviewed. The date limit was set
      to May 31th, but it was extended to September 30th of 2014 due to a new
      publication. No language restriction was used. The articles included were
      randomized trials controlled with placebo in individuals older than 12 years
      diagnosed with CIU/CSU refractory to conventional treatment, the intervention
      being, omalizumab at different doses, and the comparison, placebo. The primary
      outcome was symptom improvement according to the weekly score of urticaria
      severity (UAS7), the itch severity score (ISS), the weekly score of number of
      urticarial lesions, the dermatology life quality index, and the chronic urticaria
      quality of life questionnaire (CU-QoL). Databases were searched using the
      following Mesh or EMTREE key words including as intervention "omalizumab" or
      "humanized monoclonal antibody," compared to placebo and the disease of interest
      "urticaria" or "angioedema". The title, abstract and article were reviewed by two
      independent investigators, according to the selection criteria in each of the
      databases. An assessment of the quality of the articles was performed according
      to the bias tool from the studies of the Cochrane Collaboration. Information such
      as author data, date of study, number of participants, interventions, dose and
      frequency of administration, comparison, time of follow-up, measurements of
      weekly score of urticaria activity, pruritus severity score, weekly urticarial
      lesions, percentage of angioedema and post-treatment change were extracted.
      Frequency of adverse events and the ones suspected to be caused by the
      intervention drug were included. RESULTS: 770 records were identified in all
      databases described. 720 were eliminated for failing to meet the inclusion
      criteria in the first review or for duplicate records. 24 articles were reviewed
      by abstract, 18 additional articles were further removed, leaving 6 records for
      inclusion. An experimental study was excluded because it wasn't randomized. Five
      studies were finally included, with 1117 patients, of these 831 received a dose
      of omalizumab of 75 mg (183 patients, 16.38%), 150 mg (163 patients, 14.59%), 300
      mg (437 patients, 39.12%) or 600 mg (21 patients, 1.8%), as a single dose, or
      every 4 weeks until 24 weeks maximum. The average age was 42.07 years,
      predominantly female gender and white ethnicity. It was observed that the use of
      omalizumab 300 mg lowered the weekly scores of urticarial activity in 19.9 vs.
      6.9 on placebo (p <0.01), 19 vs 8.5 and 20.7 vs 8.01 in three studies, the weekly
      ISS (-9.2 vs. - 3.5, p <0.001, -9.8 vs -5.1 p < 0.01, -8.6 vs -4.0 and -9.4 vs 
      3.63 p <0.001 in four studies), and the percentage of angioedema-free days
      (omalizumab 95.5% vs. placebo 89.2% p <0.001, and 91.95% vs. 88.1% p <0.001 in
      two of the studies respectively). LIMITATIONS: The different doses used
      throughout the study, time of administration and follow-up periods ranged from
      single dose to monthly dose for 24 weeks. Therefore no meta-analysis of the
      review was conducted. CONCLUSIONS AND IMPLICATIONS OF THE MAIN FINDINGS: Despite
      the limitations, it is considered that omalizumab 300 mg is effective in treating
      chronic idiopathic urticaria refractory to H1 antihistamines. Further studies are
      required to determine the duration of effective treatment. REGISTRATION NUMBER OF
      THE SYSTEMATIC REVIEW: CRD42014010029 (PROSPERO. International Prospective
      Register of Systematic Reviews).

PMID- 25566333
TI  - Retrieval of distorted pipeline embolic device using snare-loop.
AB  - BACKGROUND: Flow-diverter stents are increasingly being used in the endovascular
      treatment of intracranial aneurysms. Because of this increased usage, the
      occurrence of stent malpositioning, intra-arterial distortion, or migration will
      likely increase as well. METHODS: We describe the conformational twisting and
      deformity of a pipeline embolic device (PED) stent (Covidien, EV3) within the
      carotid artery during stent placement, with the subsequent immediate removal of
      the stent by using an endovascular snare-loop to successfully remove the device.
      RESULTS: The PED can be successfully removed using a snare-loop device when
      indicated. In this case, following removal of the initial PED, the aneurysms can
      be successfully treated with the placement of a second PED. CONCLUSION: It is
      critical to have a contingency plan for the removal of malpositioned or otherwise
      deformed stents that could potentially represent significant sources of
      iatrogenic stroke.

PMID- 25566334
TI  - Extensive bilateral vertebral artery remodeling following treatment of dissection
      using pipeline embolic device.
AB  - BACKGROUND: Cerebral artery dissection remains a significant cause of stroke, and
      the mainstay of treatment has been medical management with anticoagulation,
      although flow-diverting stents have been used in some cases of arterial
      dissection resistant to medical management. METHODS: We present a case report of
      bilateral vertebral artery stenting using pipeline embolic device flow-diverting
      stents, after failed medical management of the dissection. RESULTS: This case
      demonstrated substantial subsequent vertebral arterial remodeling and good
      clinical outcome with maintenance of posterior circulation. The patient did not
      suffer any further strokes or posterior circulation symptoms following vertebral
      artery remodeling. CONCLUSION: In cases where traditional management of arterial
      dissection has not been efficacious, flow-diverting stents may be useful in
      treating dissections of the posterior cerebral circulation, even with bilateral
      involvement.

PMID- 25566330
TI  - Mito-nuclear co-evolution: the positive and negative sides of functional ancient
      mutations.
AB  - Most cell functions are carried out by interacting factors, thus underlying the
      functional importance of genetic interactions between genes, termed epistasis.
      Epistasis could be under strong selective pressures especially in conditions
      where the mutation rate of one of the interacting partners notably differs from
      the other. Accordingly, the order of magnitude higher mitochondrial DNA (mtDNA)
      mutation rate as compared to the nuclear DNA (nDNA) of all tested animals, should
      influence systems involving mitochondrial-nuclear (mito-nuclear) interactions.
      Such is the case of the energy producing oxidative phosphorylation (OXPHOS) and
      mitochondrial translational machineries which are comprised of factors encoded by
      both the mtDNA and the nDNA. Additionally, the mitochondrial RNA transcription
      and mtDNA replication systems are operated by nDNA-encoded proteins that bind
      mtDNA regulatory elements. As these systems are central to cell life there is
      strong selection toward mito-nuclear co-evolution to maintain their function.
      However, it is unclear whether (A) mito-nuclear co-evolution befalls only to
      retain mitochondrial functions during evolution or, also, (B) serves as an
      adaptive tool to adjust for the evolving energetic demands as species' complexity
      increases. As the first step to answer these questions we discuss evidence of
      both negative and adaptive (positive) selection acting on the mtDNA and nDNA
      encoded genes and the effect of both types of selection on mito-nuclear
      interacting factors. Emphasis is given to the crucial role of recurrent ancient
      (nodal) mutations in such selective events. We apply this point-of-view to the
      three available types of mito-nuclear co-evolution: protein-protein (within the
      OXPHOS system), protein-RNA (mainly within the mitochondrial ribosome), and
      protein-DNA (at the mitochondrial replication and transcription machineries). 

PMID- 25566335
TI  - Flow-diversion headaches in a patient with high-grade internal carotid artery
      stenosis.
AB  - BACKGROUND: High-grade stenosis of the internal carotid artery (ICA) may result
      in flow diversion to the external carotid artery (ECA) and its branches. Head and
      facial pain secondary to flow-diversion to ECA and increase in regional blood
      flow are under-recognized and unreported. DESIGN/METHODS: We report a patient
      with high-grade ICA stenosis and recurrent ipsilateral headaches that resolved
      after revascularization. RESULTS: A 69-year-old woman presenting with right-arm
      weakness had neuroimaging evidence of ipsilateral high-grade ICA stenosis and
      left hemispheric ischemic stroke. Her history was significant for unilateral
      recurrent headaches that clinically resolved after left ICA angioplasty and
      stenting. With prior evidence supporting extracranial vasodilatation as the
      source of pain in migraine, and current clinical observation, we propose flow
      diversion phenomenon as the connection between high-grade ICA stenosis and
      ipsilateral headache. CONCLUSION: Recognition of flow-diversion into the ECA as a
      possible mechanism for headaches may help in further understanding of ICA
      disease, its progression, and the effects of carotid revascularization on quality
      of life. Headache as a likely surrogate marker of carotid stenosis with flow
      diversion warrants more research, and may be critical in the early identification
      of significant ICA stenosis and prevention of TIA or stroke.

PMID- 25566336
TI  - Serial heart rate variability testing for the evaluation of autonomic dysfunction
      after stroke.
AB  - BACKGROUND AND PURPOSE: Autonomic dysfunction has been described as a frequent
      complication of stroke that could involve the cardiac, respiratory, sudomotor,
      and sexual systems. Cardiac autonomic dysfunction after stroke is one of the most
      recognized and has been described to increase the rate of mortality and
      morbidity. METHODS: We report two cases of stroke-one hemorrhagic and one
      ischemic-and describe heart rate variability during the patients'
      hospitalizations with improvement reported for each patient several days after
      stroke onset. RESULTS: The first case demonstrated autonomic dysfunction with
      severe reduction of HRV after a right parietal hemorrhagic stroke. The second
      case demonstrated similar findings in a patient with acute ischemic stroke. In
      both cases, normalization of heart rate variability occurred several weeks after
      stroke symptoms onset and was paralleled by a dramatic improvement of the
      clinical status. CONCLUSION: Our data established that serial HRV testing is a
      noninvasive tool that could be utilized as a marker to evaluate the dynamics of
      acute stroke.

PMID- 25566337
TI  - Neuroanatomical correlates of atrial fibrillation: a longitudinal MRI study.
AB  - BACKGROUND AND PURPOSE: To determine baseline volume and rate of volume change of
      whole brain, hippocampus, and entorhinal cortex in patients with atrial
      fibrillation. METHODS: We analyzed clinical and neuroimaging data collected as
      part of Alzheimer's Disease Neuroimaging Initiative in the United States and
      Canada. Patients with atrial fibrillation were identified based on baseline
      clinical/cognitive assessments, and age and gender-matched controls without
      atrial fibrillations were selected (1:1 ratio). All participants underwent 1.5 T
      structural magnetic resonance imaging (MRI) at specified intervals (6 or 12
      months) for 2-3 years. RESULTS: A total of 33 persons with atrial fibrillation
      were included. There was no difference in whole brain and ventricular volumes at
      baseline MRI between cases and controls. There was significantly lower entorhinal
      cortex volume on right (p = 0.01) and left (p = 0.01) sides in patients with
      atrial fibrillation. There was significantly lower volume for middle temporal
      lobes on right (p = 0.04) and left (p = 0.001) sides. The rate of progression of
      atrophy in entorhinal cortex and middle temporal lobes was not different between
      patients with atrial fibrillation and controls. CONCLUSIONS: The association of
      atrial fibrillation with volume loss in entorhinal cortex and middle temporal
      lobes may provide new insights into pathophysiology of atrial fibrillation.

PMID- 25566338
TI  - Internal carotid artery stenosis associated with giant cell arteritis: case
      report and discussion.
AB  - BACKGROUND: Cerebrovascular ischemic events associated with giant cell arteritis
      (GCA) are uncommon and have been reported in 3%-4% of patients. We describe a
      case report of GCA associated with intracranial stenosis and review various
      angiographic findings. CASE PRESENTATION: A 66-year-old man presented with
      worsening headache and vision loss. A recent magnetic resonance angiogram of the
      head and neck showed multiple intracranial stenosis. Cerebrospinal fluid (CSF)
      analysis demonstrated increased protein of 135.6 mg/dL, with two white blood
      cells/uL. No bacteria were observed in the CSF on gram staining, and cultures
      were negative for bacterial growth. Erythrocyte sedimentation rate was noted to
      be 14 mm/h, and C-reactive protein was 1.514 mg/L at admission. Human
      immunodeficiency virus (HIV) and hepatitis panels were negative. On digital
      subtraction angiography, patient had predominantly narrowing and irregularities
      in petrous and cavernous segments of the internal carotid arteries bilaterally.
      The diagnosis of GCA was confirmed by temporal artery biopsy. He was treated with
      steroids, and a followup angiogram 6 weeks later showed minimal resolution of the
      angiographic findings. Patient reported complete resolution of headaches and
      visual loss. CONCLUSION: Bilateral internal carotid arteries stenosis may be seen
      in patients presenting with typical symptoms of GCA and may persist after steroid
      treatment despite resolution of clinical symptoms.

PMID- 25566339
TI  - Thrombolytic treatment for in-hospital ischemic strokes in United States.
AB  - BACKGROUND: Despite the recent emphasis on protocols for emergent triage and
      treatment of in-hospital acute ischemic stroke, there is little data on outcomes
      of patients receiving thrombolytics for in-hospital ischemic strokes. The
      objective of this study was to determine the rates of patients with in-hospital
      ischemic stroke treated with thrombolytics and to compare outcomes with patients
      treated on admission. METHODS: We analyzed an 8-year data (2002-2010) from the
      National Inpatient Survey. We identified patients who had in-hospital ischemic
      strokes (thrombolytic treatment after 1 day of hospitalization) and those treated
      on admission day. We compared demographics, clinical characteristics, in hospital
      complications and procedures, length of stay, hospitalization charges, and
      discharge disposition between the two groups. RESULTS: A total of 25193 (19%) and
      109784 (81%) patients received thrombolytics for in-hospital and on admission
      acute strokes, respectively. In-hospital complications including intracerebral
      hemorrhage, pneumonia, deep venous thrombosis, pulmonary embolism and sepsis and
      in-hospital procedures such as cerebral angiography, endovascular thrombectomy,
      carotid artery stent placement, carotid endarterectomy, intubation, mechanical
      ventilation, gastrostomy, transfusion of blood products were significantly higher
      in the in-hospital stroke group. In a multivariate analysis, those who were
      treated following in-hospital stroke had higher rates of in-hospital mortality
      (odds ratio (OR) 1.1, 95% confidence interval (CI) 1.0-1.3, p = 0.05), and post
      thrombolytic ICH (OR 1.2, CI 1.0-1.3, p = 0.03). CONCLUSION: One out of every
      five acute ischemic stroke patients treated with thrombolytics is receiving the
      treatment for in-hospital stroke. The higher mortality and complicated
      hospitalization in such patients needs to be recognized.

PMID- 25566341
TI  - Percutaneous inferior cervical sympathetic ganglion blockade for the treatment of
      ventricular tachycardia storm: case report and review of the literature.
AB  - Running Title: Sympathetic Block for Ventricular Tachycardia Storm. INTRODUCTION:
      We present the case of a patient with ventricular tachycardia storm refractory to
      medical therapy and multiple catheter ablations, successfully managed by
      percutaneous left inferior cervical sympathetic ganglion block. SUMMARY: A 70
      year-old man with a history of ischemic cardiomyopathy and previous placement of
      implantable defibrillator developed intractable ventricular tachycardia
      recalcitrant to intravenous amiodarone, lidocaine, and multiple catheter
      ablations with radiofrequency energy and direct current. The patient received
      numerous defibrillator shocks that did not result in sustained restoration of
      sinus rhythm. A percutaneous inferior cervical sympathetic ganglion block was
      performed under fluoroscopic guidance, with the administration of bupivacaine by
      infiltration of the tissue between the left internal carotid artery and the
      cervical vertebral bodies. RESULTS: Two and a half hours after the procedure,
      ventricular tachycardia converted to sinus rhythm. One month after discharge from
      the hospital, the patient remained free from sustained ventricular tachycardia
      and did not report discharges from his implantable defibrillator. CONCLUSION:
      Percutaneous cervical sympathetic ganglion blockade appears to be an effective
      intervention in the treatment of ventricular tachycardia storm. Additional data
      are required before incorporating this technique into the management algorithm of
      incessant ventricular tachycardia.

PMID- 25566340
TI  - A comparison of different transarterial embolization techniques for direct
      carotid cavernous fistulas: a single center experience in 32 patients.
AB  - OBJECTIVE: Transarterial treatment of direct carotid cavernous fistulas (DCCF)
      via embolic materials has been well documented. This study reports, validates,
      and compares with existing literature our experience treating DCCFs via
      endovascular approaches by using detachable balloons, coils, and covered stents.
      METHODS: Between June 2006 to October 2011, 32 patients (21 male, 11 female) with
      32 DCCFs (30 traumatic, 2 spontaneous cavernous ICA aneurysms) were embolized
      endovascularly. Followup was performed for at least 6 months. RESULTS: Among the
      32 DCCFs, 21 (65.6%) were embolized using detachable balloons, eight (25.0%) with
      coils, one (3.1%) with balloons and coils, and two (6.3%) with covered stents.
      Complete DCCF obliteration was achieved in 31 (96.9%) cases. One fistula failed
      to respond due to premature balloon detachment. Intracranial bruit in 31 (100%)
      chemosis and exophthalmos in 28 (100%) cases resolved after embolization. Visual
      acuity and oculomotor palsy improved in 18 (90%) and 18 (69.2%) cases,
      respectively. There was no evidence of DCCF recurrence. Thirteen DCCFs were
      followed up by MRI and five by DSA. In these cases, four (4/13, 30.8%) balloon
      embolized DCCFs showed pseudoaneurysms. Three patients were asymptomatic; one had
      minor left oculomotor palsy. CONCLUSIONS: Our results correlate and reinforce
      literature regarding endovascular treatment of DCCFs. Application of
      Transarterial embolization with detachable balloons, despite extensive use has
      been decreasing. Coil embolization is an effective and safe alternative for
      treatment, especially when balloon embolization fails. Covered stent placement
      may be used as another alternative for selected cases.

PMID- 25566342
TI  - The association between cardiovascular risk factors and progressive hippocampus
      volume loss in persons with Alzheimer's disease.
AB  - BACKGROUND: We performed the current study to test the hypothesis that the
      aggregation of cardiovascular risk factors in patients with Alzheimer's disease
      (AD) was associated with a higher rate of volume loss in the hippocampus and
      progression of cognitive deficits. METHODS: A total of 103 persons with AD were
      included (65 men and 38 women, average age of 74.5 +/- 0.8 years). All
      participants underwent 1.5 T structural magnetic resonance imaging (MRI), at
      specified intervals (6 or 12 months) for 2-3 years. We determined the rates of
      hippocampus, whole brain, ventricle, middle temporal lobe, fusiform, and
      entorhinal volume loss (in cubic millimeter/year) for all patients with AD,
      separately for 0-6 months, 6-12 months and 0-12, 12-18 and 18-24 months scan
      intervals. RESULTS: There were significant differences in Mini-Mental State
      Examination (MMSE) (p = 0.001) and Alzheimer's disease Assessment Scale (ADAS) (p
      = 0.01) scale scores between persons with and without hypertension and in MMSE (p
      = 0.04) and Clinical Dementia Rating (CDR) (p = 0.008) scale scores between
      persons with and without hyperlipidemia. There were no significant differences in
      MMSE, ADAS, and CDR scales scores between persons with and without diabetes
      mellitus and cigarette smoking. There were no significant differences in regional
      brain volume loss in those with or without cardiovascular risk factors.
      CONCLUSIONS: Cardiovascular risk factors have a significant influence on the
      progression of cognitive deficits in patients with AD. The progression of
      cognitive deficits in patients with AD is not mediated by progressive hippocampal
      volume loss.

PMID- 25566343
TI  - Unsustainable hospital charges are incurred in the treatment of Medicare
      beneficiaries admitted with subarachnoid hemorrhage.
AB  - INTRODUCTION: Rising medical care expenditures and the unchanging Medicare
      reimbursements have placed restraints on the health care delivery system.
      OBJECTIVE: The goal of this study is to identify the magnitude and determinants
      of discrepancy between hospitalization charges and Medicare re-imbursement
      observed in the management of Medicare beneficiaries admitted with aneurysmal
      subarachnoid hemorrhage in the United States. METHODS: Patients entered in the
      Nationwide Inpatient Sample between 2002 and 2010, with a ruptured intracranial
      aneurysm who underwent either surgical or endovascular treatment were included in
      the study. Factors associated with higher discrepancy between hospitalization
      charges and Medicare re-imbursement were identified. RESULTS: Discrepancies in
      hospital charges and Medicare reimbursement associated with endovascular and
      surgical treatment have increased over the decade. The median discrepancy per
      patient for Medicare patients aged 65 years and older treated surgically or
      endovascularly for a ruptured aneurysm from 2009 to 2010 was $177,380. The
      predictors of higher than median discrepancy(charges versus reimbursement),
      included Hispanic ethnicity (OR 2.1, 95% CI 1.1-3.9, p = 0.02), urinary tract
      infection (OR 2.0, 95% CI 1.4-2.8, p = <0.001), pneumonia (OR 3.0, 95% CI 1.8
      4.8, p = <0.001), deep vein thrombosis (OR 2.5, 95% CI 1.2-5.2, p = 0.02), and
      pulmonary embolism (OR 18, 95% CI 2.0-169, pp = 0.01). CONCLUSIONS: There is a
      growing gap between hospital charges and Medicare reimbursement. If hospitals
      continue to be reimbursed at significantly lower rates than charges incurred,
      this current system may be unsustainable due to losses incurred by hospitals.
      ABBREVIATIONS: AHRQAgency for Healthcare Research and QualityCMSCenters for
      Medicare and Medicaid servicesNISNationwide Inpatient Sample.

PMID- 25566344
TI  - Liquid embolization of brain arteriovenous malformation using novel detachable
      tip micro catheter: a technical report.
AB  - BACKGROUND AND IMPORTANCE: Liquid embolization using Onyx(r) of brain
      arteriovenous malformations (AVMs) is sometimes limited by micro catheter
      retention by Onyx(r) cast during the disengagement process. Use of the new
      detachable tip micro catheter is presented in this report. CLINICAL PRESENTATION:
      Two feeding arteries of a previously ruptured brain AVM in a 62-year-old man were
      embolized by Onyx 18 prior to surgery using the new ApolloTM micro catheter with
      the detachable-tip (30 mm) was utilized. The arterial feeders were accessed
      without difficulty by micro catheter, guided by 0.010" microwire. Onyx reflux
      around the distal end of the micro catheter was necessary for effective
      embolization of arteriovenous fistulous components of brain AVM. The micro
      catheter was successfully retracted after embolization in both feeding arteries,
      with distal end detachment seen in one but not the other arterial embolization.
      No arterial thrombosis, vasospasm, dissection, or rupture was seen at respective
      sites of disengagement. CONCLUSION: Use of the new micro catheters with
      detachable-tip design allowed prolonged Onyx(r) injection times, safe micro
      catheter disengagement, without any limitations in accessing target arterial
      feeders.

PMID- 25566345
TI  - Effect of intra-arterial injection of lidocaine and methyl-prednisolone into
      middle meningeal artery on intractable headaches.
AB  - The present report describes the effect of intra-arterial injection of a dose of
      40 mg lidocaine and 20 mg methylprednisolone into the middle meningeal artery of
      two patients suffering from severe headaches. The effect of injection of
      lidocaine and methylprednisolone was short lasting with effect manifesting within
      5 min and lasting 5-8 h after injection. Both patients reported improvement in
      headache intensity after 24 h post-procedure. Intra-arterial injection of
      lidocaine and methylprednisolone may represent another treatment strategy for
      headaches not responsive to standard treatment. 

PMID- 25566346
TI  - Mean transit time on Aquilion ONE and its utilization in patients undergoing
      acute stroke intervention.
AB  - BACKGROUND: Neuroimaging techniques have been beneficial in identifying patients
      with salvageable penumbra. We sought to validate the mean transit time (MTT) map
      on computed tomography perfusion (CTP) imaging utilizing an Aquilion ONE computed
      tomography (CT) scanner running a singular value decomposition plus algorithm in
      patients with acute large vessel ischemic stroke who underwent endovascular
      therapy. METHODS: We conducted a retrospective analysis of consecutive patients
      presenting to the emergency room who met the following criteria: 1) had a large
      vessel acute ischemic stroke; 2) had a high-quality whole-brain CTP; 3) treated
      with endovascular therapy; and 4) received a follow-up MRI with diffusion
      weighted imaging (DWI) within 48 h. A blinded neurologist, neuroradiologist, and
      neurosurgeon utilized the Vitrea software to process the images independently
      using an infarct perimeter method. RESULTS: Twelve patients met the inclusion
      criteria. A comparison was made between the volumes of infarct core (IC)
      utilizing MTT and DWI after accounting for other co-founding factors (i.e.,
      recanalization rate, time between CT and MRI, time to achieve recanalization, and
      IV t-PA administration). MTT was redefined as capillary MTT (cMTT) which
      represented evolving capillary flow influenced by hypoxia induced
      vasodilation/vasoconstriction. We divided the patients into two groups based on
      the degree of reperfusion: A) patients with a TICI score of IIb or III and B)
      patients with a TICI score of I or IIa. We compared the two groups and found that
      the rate of reperfusion significantly affected the volume of the infarct on MTT
      when compared with a follow-up MRI (p value < 0.04). Furthermore, we found a
      strong positive correlation R(2) = 0.6 between the average MTT infarct volume and
      the final DWI MR volumes. In addition, the averaged MTT IC volumes were 84% of
      the final averaged DWI IC volumes. CONCLUSION: Although further studies are
      required to validate this retrospective study, preliminary data suggest that cMTT
      maps can be a valuable and accurate tool in the assessment of patients with acute
      stroke who may benefit from aggressive endovascular therapy.

PMID- 25566347
TI  - Diffuse cerebral microhemorrhages in a patient with adult-onset Pompe's disease:
      a case report.
AB  - BACKGROUND: Pompe's disease is a glycogen storage disease that manifests as
      progressive neuropathy, and myopathy. There are a few reports of vasculopathy in
      this disease, thought to be from small- and medium-vessel arteriopathy. We
      present a case of late-onset Pompe's disease with microhemorrhages and review of
      the pertinent literature. METHODS: We describe a case of microhemorrhages in a
      patient with known late-onset Pompe's disease. RESULTS: Our patient was noted to
      have numerous microhemorrhages concentrated in the posterior circulation
      distribution in what can best be described as central microhemorrhages, distinct
      from the pattern seen in amyloid angiopathy. Previous autopsy studies have found
      vacuoles in the vessel wall, resulting in small aneurysms as a part of the Pompe
      syndrome. CONCLUSIONS: There is an accumulating body of evidence that suggests
      cerebral vasculopathy as one of the primary manifestations of adult-onset Pompe's
      disease. This is manifested as dolichoectasia of basilar artery, aneurysms, and
      microhemorrhages that are central in distribution. The primary pathology is
      thought to be glycogen deposition in small- and medium-sized intracranial
      vessels. Controlling blood pressure aggressively and screening intracranial
      vascular imaging are recommended. Further definition of the syndrome is
      continuing from phenotypic and genotypic dimensions.

PMID- 25566348
TI  - Complete genome sequence of the lignin-degrading bacterium Klebsiella sp. strain
      BRL6-2.
AB  - In an effort to discover anaerobic bacteria capable of lignin degradation, we
      isolated Klebsiella sp. strain BRL6-2 on minimal media with alkali lignin as the
      sole carbon source. This organism was isolated anaerobically from tropical forest
      soils collected from the Bisley watershed at the Ridge site in the El Yunque
      National Forest in Puerto Rico, USA, part of the Luquillo Long-Term Ecological
      Research Station. At this site, the soils experience strong fluctuations in redox
      potential and are characterized by cycles of iron oxidation and reduction. Genome
      sequencing was targeted because of its ability to grow on lignin anaerobically
      and lignocellulolytic activity via in vitro enzyme assays. The genome of
      Klebsiella sp. strain BRL6-2 is 5.80 Mbp with no detected plasmids, and includes
      a relatively small arsenal of genes encoding lignocellulolytic carbohydrate
      active enzymes. The genome revealed four putative peroxidases including
      glutathione and DyP-type peroxidases, and a complete protocatechuate pathway
      encoded in a single gene cluster. Physiological studies revealed Klebsiella sp.
      strain BRL6-2 to be relatively stress tolerant to high ionic strength conditions.
      It grows in increasing concentrations of ionic liquid (1-ethyl-3-methyl
      imidazolium acetate) up to 73.44 mM and NaCl up to 1.5 M. 

PMID- 25566351
TI  - Discovery of functional non-coding conserved regions in the alpha-synuclein gene
      locus.
AB  - Several single nucleotide polymorphisms (SNPs) and the Rep-1 microsatellite
      marker of the alpha-synuclein ( SNCA) gene have consistently been shown to be
      associated with Parkinson's disease, but the functional relevance is unclear.
      Based on these findings we hypothesized that conserved cis-regulatory elements in
      the SNCA genomic region regulate expression of SNCA, and that SNPs in these
      regions could be functionally modulating the expression of SNCA, thus
      contributing to neuronal demise and predisposing to Parkinson's disease. In a
      pair-wise comparison of a 206kb genomic region encompassing the SNCA gene, we
      revealed 34 evolutionary conserved DNA sequences between human and mouse. All
      elements were cloned into reporter vectors and assessed for expression modulation
      in dual luciferase reporter assays.  We found that 12 out of 34 elements
      exhibited either an enhancement or reduction of the expression of the reporter
      gene. Three elements upstream of the SNCA gene displayed an approximately 1.5
      fold (p<0.009) increase in expression. Of the intronic regions, three showed a
      1.5 fold increase and two others indicated a 2 and 2.5 fold increase in
      expression (p<0.002). Three elements downstream of the SNCA gene showed 1.5 fold
      and 2.5 fold increase (p<0.0009). One element downstream of SNCA had a reduced
      expression of the reporter gene of 0.35 fold (p<0.0009) of normal activity. Our
      results demonstrate that the SNCA gene contains cis-regulatory regions that might
      regulate the transcription and expression of SNCA. Further studies in disease
      relevant tissue types will be important to understand the functional impact of
      regulatory regions and specific Parkinson's disease-associated SNPs and its
      function in the disease process. 

PMID- 25566349
TI  - Hydrodynamics of DNA confined in nanoslits and nanochannels.
AB  - Modeling the dynamics of a confined, semi exible polymer is a challenging
      problem, owing to the complicated interplay between the configurations of the
      chain, which are strongly affected by the length scale for the confinement
      relative to the persistence length of the chain, and the polymer-wall
      hydrodynamic interactions. At the same time, understanding these dynamics are
      crucial to the advancement of emerging genomic technologies that use confinement
      to stretch out DNA and "read" a genomic signature. In this mini-review, we begin
      by considering what is known experimentally and theoretically about the friction
      of a wormlike chain such as DNA confined in a slit or a channel. We then discuss
      how to estimate the friction coefficient of such a chain, either with dynamic
      simulations or via Monte Carlo sampling and the Kirk-wood pre-averaging
      approximation. We then review our recent work on computing the diffusivity of DNA
      in nanoslits and nanochannels, and conclude with some promising avenues for
      future work and caveats about our approach.

PMID- 25566350
TI  - Case Report: Mammary and rectal metastases from an ovarian cancer: report of two
      cases and review of literature.
AB  - In this paper we report two interesting cases of metastatic ovarian cancer. The
      first case is a patient who developed rectal and breast metastases mimicking an
      inflammatory breast cancer. In the second case, subclinical breast and axillary
      lymph node metastases were revealed by PET/CT. Metastases in the breast
      originating from solid tumors are extremely rare. The ovarian primitive is the
      fourth most common origin. The occurrence of breast metastasis is associated with
      an advanced disease and a poor prognosis. Their incidence is increasing since
      they are found more often due to better imaging techniques and to better
      treatment that, accordingly, improve patients' survival. Thus, unusual sites of
      metastases are more and more reported. Indeed, some authors reported the
      occurrence of colorectal metastases from ovarian cancer. However, they remain
      much less frequent. 

PMID- 25566352
TI  - Case Report: Rare occurrence of Pseudomonas aeruginosa osteomyelitis of the right
      clavicle in a patient with IgA nephropathy.
AB  - We describe the case of a 47 year old patient with proven primary IgA nephropathy
      who presented with osteomyelitis of the medial end of the right clavicle. The
      patient was not on immunosuppressive medications. He underwent aspiration
      curettage and CT scan of the clavicle which yielded pus that grew Pseudomonas
      aeruginosa. Following treatment with appropriate antibiotic therapy the patient
      presented a complete recovery of the lesion with no loss of renal function. This
      case highlights the importance of positive cultures in the choice of the
      appropriate therapy in an extremely rare case of an immunocompetent patient with
      osteomyelitis of the clavicle. 

PMID- 25566353
TI  - Putting the BMC into psychology publishing.

PMID- 25566354
TI  - Negativland - a home for all findings in psychology.
AB  - Psychology has been historically plagued by the under-reporting of both
      replications and null findings. The avoidance of these core ingredients of
      scientific practice means that the psychology literature is unquestionably
      distorted. The bias in psychology is pervasive and systemic, afflicting
      researchers, reviewers, editors and journals, all of whom are wed to pursuing the
      novel and the curious at the expense of the reliable. Psychology therefore
      operates in a manner that is askew of other sciences, with the links between
      replicability and believability seemingly much weaker. Additional problems follow
      from the distorted way that psychology currently operates - including spinning
      findings, publication bias, and sadly, outright fraud. Such problems represent a
      serious challenge for psychologists to get their house-in-order - and one step is
      to make sure that replications and null findings find a home in psychology rather
      than remain our dirty little secrets that further eat away at the credibility of
      our science. 

PMID- 25566356
TI  - An interview with Irismar Reis de Oliveira, Section Editor for Clinical
      Psychology and Psychotherapy.

PMID- 25566355
TI  - Evaluation of emotion processing in HIV-infected patients and correlation with
      cognitive performance.
AB  - BACKGROUND: Facial emotion recognition depends on cortical and subcortical
      networks. HIV infection of the central nervous system can damage these networks,
      leading to impaired facial emotion recognition. METHODS: We performed a cross
      sectional single cohort study consecutively enrolling HIV + subjects during
      routine outpatient visits. Age, gender and education-matched HIV-negative healthy
      individuals were also selected. Subjects were submitted to a Facial Emotion
      Recognition Test, which assesses the ability to recognize six basic emotions
      (disgust, anger, fear, happiness, surprise, sadness). The score for each emotion
      and a global score (obtained by summing scores for each emotion) were analyzed.
      General cognitive status of patients was also assessed. RESULTS: A total of 49
      HIV + and 20 HIV - subjects were enrolled. On the Facial Emotion Recognition
      Test, ANOVA revealed a significantly lower performance of HIV + subjects than
      healthy controls in recognizing fear. Moreover, fear facial emotion recognition
      was directly correlated with Immediate Recall of Rey Words. The lower the
      patients' neurocognitive performance the less accurate they were in recognizing
      happiness. AIDS-defining events were negatively related to the correct
      recognition of happiness. CONCLUSIONS: Fear recognition deficit in HIV + patients
      might be related to the impaired function of neural networks in the
      frontostriatal system. AIDS events, including non-neurological ones, may have a
      negative effect on this system. Inclusion of an emotion recognition test in the
      neuropsychological test battery could help clinicians during the long term
      management of HIV-infected patients, to better understand the cognitive
      mechanisms involved in the reduction of emotion recognition ability and the
      impact of this impairment on daily life.

PMID- 25566357
TI  - A rasch model to test the cross-cultural validity in the positive and negative
      syndrome scale (PANSS) across six geo-cultural groups.
AB  - BACKGROUND: The objective of this study was to examine the cross-cultural
      differences of the PANSS across six geo-cultural regions. The specific aims are
      (1) to examine measurement properties of the PANSS; and (2) to examine how each
      of the 30 items function across geo-cultural regions. METHODS: Data was obtained
      for 1,169 raters from 6 different regions: Eastern Asia (n = 202), India (n =
      185), Northern Europe (n = 126), Russia & Ukraine (n = 197), Southern Europe (n =
      162), United States (n = 297). A principle components analysis assessed
      unidimensionality of the subscales. Rasch rating scale analysis examined cross
      cultural differences among each item of the PANSS. RESULTS: Lower item values
      reflects items in which raters often showed less variation in the scores; higher
      item values reflects items with more variation in the scores. Positive Subscale:
      Most regions found item P5 (Excitement) to be the most difficult item to score.
      Items varied in severity from -0.93 [item P6. Suspiciousness/persecution (USA) to
      0.69 item P4. Excitement (Eastern Asia)]. Item P3 (Hallucinatory Behavior) was
      the easiest item to score for all geographical regions. Negative Subscale: The
      most difficult item to score for all regions is N7 (Stereotyped Thinking) with
      India showing the most difficulty Delta = 0.69, and Northern Europe and the
      United States showing the least difficulty Delta = 0.21, each. The second most
      difficult item for raters to score was N1 (Blunted Affect) for most countries
      including Southern Europe (Delta = 0.30), Eastern Asia (Delta = 0.28), Russia &
      Ukraine (Delta = 0.22) and India (Delta = 0.10). General Psychopathology: The
      most difficult item for raters to score for all regions is G4 (Tension) with
      difficulty levels ranging from Delta = 1.38 (India) to Delta = 0.72. CONCLUSIONS:
      There were significant differences in response to a number of items on the PANSS,
      possibly caused by a lack of equivalence between the original and translated
      versions, cultural differences among interpretation of items or scoring
      parameters. Knowing which items are problematic for various cultures can help
      guide PANSS training and make training specialized for specific geographical
      regions.

PMID- 25566358
TI  - Suicide prevention in schizophrenia spectrum disorders and psychosis: a
      systematic review.
AB  - BACKGROUND: The incidence of suicide is high among patients with schizophrenia
      spectrum disorders and psychosis. A systematic review was performed to
      investigate the effectiveness of psychosocial interventions in reducing suicidal
      behaviour among patients with schizophrenia spectrum disorders and psychosis.
      METHODS: Cochrane, PubMed and PsycINFO databases were searched to January 2012.
      Additional materials were obtained from reference lists. Randomised Controlled
      Trials describing psychosocial interventions for psychotic disorders with
      attention placebo, treatment as usual (TAU), no intervention or waitlist control
      groups were included. RESULTS: In total, 11,521 abstracts were identified. Of
      those, 10 papers describing 11 trials targeting psychosocial interventions for
      reducing suicidal behaviour in patients with schizophrenia spectrum disorders and
      psychosic symptoms or disorders met the inclusion criteria. Odds Ratios
      describing the likelihood of a reduction in suicidal behaviour or ideation ranged
      from 0.09 to 1.72 at post-test and 0.13 to 1.48 at follow-up. CONCLUSIONS:
      Psychosocial interventions may be effective in reducing suicidal behaviour in
      patients with schizophrenia spectrum disorders and psychosis, although the
      additional benefit of these interventions above that contributed by a control
      condition or treatment-as-usual is not clear.

PMID- 25566359
TI  - Development and preliminary testing of the psychosocial adjustment to hereditary
      diseases scale.
AB  - BACKGROUND: The presence of Lynch syndrome (LS) can bring a lifetime of
      uncertainty to an entire family as members adjust to living with a high lifetime
      cancer risk. The research base on how individuals and families adjust to genetic
      linked diseases following predictive genetic testing has increased our
      understanding of short-term impacts but gaps continue to exist in knowledge of
      important factors that facilitate or impede long-term adjustment. The failure of
      existing scales to detect psychosocial adjustment challenges in this population
      has led researchers to question the adequate sensitivity of these instruments.
      Furthermore, we have limited insight into the role of the family in promoting
      adjustment. METHODS: The purpose of this study was to develop and initially
      validate the Psychosocial Adjustment to Hereditary Diseases (PAHD) scale. This
      scale consists of two subscales, the Burden of Knowing (BK) and Family
      Connectedness (FC). Items for the two subscales were generated from a qualitative
      data base and tested in a sample of 243 participants from families with LS.
      RESULTS: The Multitrait/Multi-Item Analysis Program-Revised (MAP-R) was used to
      evaluate the psychometric properties of the PAHD. The findings support the
      convergent and discriminant validity of the subscales. Construct validity was
      confirmed by factor analysis and Cronbach's alpha supported a strong internal
      consistency for BK (0.83) and FC (0.84). CONCLUSION: Preliminary testing suggests
      that the PAHD is a psychometrically sound scale capable of assessing psychosocial
      adjustment. We conclude that the PAHD may be a valuable monitoring tool to
      identify individuals and families who may require therapeutic interventions.

PMID- 25566360
TI  - Neuropsychological profile according to the clinical stage of young persons
      presenting for mental health care.
AB  - BACKGROUND: Clinical staging of mental disorders proposes that individuals can be
      assessed at various sub-syndromal and later developed phases of illness. As an
      adjunctive rating, it may complement traditional diagnostic silo-based
      approaches. In this study, we sought to determine the relationships between
      clinical stage and neuropsychological profile in young persons presenting to
      youth-focused mental health services. METHODS: Neuropsychological testing of 194
      help-seeking young people (mean age 22.6 years, 52% female) and 50 healthy
      controls. Clinical staging rated 94 persons as having an 'attenuated syndrome'
      (stage 1b) and 100 with a discrete or persistent disorder (stage 2/3). RESULTS:
      The discrete disorder group (stage 2/3) showed the most impaired
      neuropsychological profile, with the earlier stage (1b) group showing an
      intermediate profile, compared to controls. Greatest impairments were seen in
      verbal memory and executive functioning. To address potential confounds created
      by 'diagnosis', profiles for those with a mood syndrome or disorder but not
      psychosis were also examined and the neuropsychological impairments for the stage
      2/3 group remained. CONCLUSIONS: The degree of neuropsychological impairment in
      young persons with mental disorders appears to discriminate those with attenuated
      syndromes from those with a discrete disorder, independent of diagnostic status
      and current symptoms. Our findings suggest that neuropsychological assessment is
      a critical aspect of clinical evaluation of young patients at the early stages of
      a major psychiatric illness.

PMID- 25566361
TI  - Validation of the 10-item Chinese perceived stress scale in elderly service
      workers: one-factor versus two-factor structure.
AB  - BACKGROUND: Despite its popularity, the psychometric properties of the 10-item
      Chinese Perceived Stress Scale (CPSS-10) in working adults are yet to be
      evaluated. METHODS: This study examined CPSS-10 in elderly service workers
      through a questionnaire survey. The sample was randomly split into two for
      exploratory (EFA) and confirmatory factor analysis (CFA). RESULTS: A high
      response rate (93%) was achieved, resulting in 992 completed questionnaires. EFA
      with the first split sample favored a two-factor over a one-factor solution. The
      second factor had eigenvalue 2.00 and provided 19.95% explained variance. In CFA
      with the second split sample, the two-factor structure showed satisfactory
      goodness-of-fit (CFI = 0.93, RMSEA = 0.06) while the one-factor structure showed
      poor data fit (CFI = 0.62, RMSEA = 0.14). Further analyses on the two-factor
      structure revealed that the whole scale and two subscales had acceptable internal
      consistency (Cronbach's alphas = 0.67 to 0.78). The total score was positively
      associated with perceived workload and burnout (r = 0.17 to 0.48), but negatively
      with work engagement (r = -0.13 to -0.30). In contrary to previous studies, a low
      inter-factor correlation (r = -0.08) was revealed. CONCLUSIONS: CPSS-10 showed a
      stable two-factor structure with satisfactory internal consistency and construct
      validity.

PMID- 25566362
TI  - Sex discriminations made on the basis of ambiguous visual cues can be affected by
      the presence of an olfactory cue.
AB  - BACKGROUND: Almost every interpersonal interaction is mediated by the sex of the
      individuals involved. Visual, auditory, and olfactory cues provide individuals
      with the opportunity to discriminate the sex of others from a distance and so
      prepare sex-appropriate behaviours for any impending interaction. The usefulness
      of that important social skill is mediated by the reliability of the sensory
      information. Sometimes cues in one domain will be ambiguous, and the perceptual
      processes mediating sex perceptions will need to integrate information from
      across the senses for better reliability. With that in mind, the experiment
      reported here was designed to explore the effect of olfactory-visual interactions
      on sex perceptions. METHODS: Observers were presented visually with point-light
      walkers that were sexually ambiguous (not unequivocally female or male). They
      were asked to judge, using a two-alternative forced choice paradigm, the sex of
      each walker. Tested on two occasions, observers unknowingly made sex judgements
      in the presence or absence of pads soaked in male sweat. RESULTS: The presence of
      male sweat was associated with higher proportions of 'male' judgements of both
      ambiguous female and ambiguous male walkers (F1,19 = 24.11, p < 0.01).
      CONCLUSION: These findings suggest that olfactory cues can modulate visual sex
      discriminations made on the basis of biological motion cues. Importantly, they
      seem to do so even when the olfactory cue is not consciously perceived,
      suggesting these effects are mediated by perceptual rather than cognitive
      processes. These findings suggest that there exist cortical processes mediating
      sex perceptions that are capable of integrating visual and olfactory information.
      What is important is that this sensory integration takes place without conscious
      knowledge and that appropriate behaviour modifications may occur automatically.

PMID- 25566363
TI  - Promoting sense of coherence: Salutogenesis among people with psoriasis
      undergoing patient education in climate therapy.
AB  - BACKGROUND: There is a need for further investigation of sense of coherence
      (SOC), the central concept of salutogenesis, and its relationship with long-term
      illnesses such as psoriasis. The aim of this study is to investigate the
      development of SOC during patient education in the context of climate therapy and
      to explore factors that may predict changes in SOC among people with psoriasis.
      METHODS: A prospective design included a baseline assessment and two follow-ups
      after a 3-week patient education and climate therapy programme (follow-up 1) and
      again 3 months later (follow-up 2). A total of 254 adults (aged 20-80) with
      psoriasis participated. SOC was measured by the SOC Questionnaire, illness
      perception was measured by the Revised Illness Perception Questionnaire, and
      positive and active engagement in life was measured by the positive and active
      engagement subscale of the Health Education Impact Questionnaire. Paired-sample t
      tests were used to evaluate changes in SOC from the baseline to follow-up.
      Multiple linear regression was used to analyse the ability of socio-demographic
      and clinical variables, illness perception and positive and active engagement in
      life to predict the changes in SOC. RESULTS: The SOC score changed significantly
      by 2.65 points, (95% CI = 0.621, 3.685) from the baseline to follow-up 1. SOC
      score was still improved by 1.15 points (95% CI = 0.073, 0.223) at follow-up 2.
      Baseline and change in positive and active engagement in life were linked to
      change in SOC with standardized beta 0.170 (95% CI = 0.024, 0.319) and 0.259 (95%
      CI = 0.092, 0.428), respectively. In addition illness coherence perception at
      baseline and change in emotional representations were significantly associated
      with the change in SOC with standardized beta 0.212 (95% CI = 0.073, 0.361) and 
      0.270 (95% CI = -0.481, -0,077), respectively. CONCLUSIONS: SOC improved
      significantly from before to after patient education in the context of climate
      therapy. The results indicate that improving positive and active engagement in
      life, coping with emotional distress and a coherent understanding of the illness
      might provide important opportunities to improve SOC among people with psoriasis.

PMID- 25566364
TI  - Using the yes/no recognition response pattern to detect memory malingering.
AB  - BACKGROUND: Detection of feigned neurocognitive deficits is a challenge for
      neuropsychological assessment. We conducted two studies to examine whether memory
      malingering is characterized by an elevated proportion of false negatives during
      yes/no recognition testing and whether this could be a useful measure for
      assessment. METHODS: Study 1 examined 51 participants claiming compensation due
      to mental disorders, 51 patients with affective disorders not claiming
      compensation and 13 patients with established dementia. Claimants were sub
      divided into suspected malingerers (n = 11) and non-malingerers (n = 40)
      according to the Test of Memory Malingering (TOMM). In study 2, non-clinical
      participants were instructed to either malinger memory deficits due to depression
      (n = 20), or to perform normally (n = 20). RESULTS: In study 1, suspected
      malingerers had more false negative responses on the recognition test than all
      other groups and false negative responding was correlated with Minnesota
      Multiphasic Personality Inventory (MMPI) measures of deception. In study 2, using
      a cut-off score derived from the clinical study, the number of false negative
      responses on the yes/no recognition test predicted group membership with
      comparable accuracy as the TOMM, combining both measures yielded the best
      classification. Upon interview, participants suspected the TOMM more often as a
      malingering test than the yes/no recognition test. CONCLUSION: Results indicate
      that many malingers adopt a strategy of exaggerated false negative responding on
      a yes/no recognition memory test. This differentiates them from both dementia and
      affective disorder, recommending false negative responses as an efficient and
      inconspicuous screening measure of memory malingering.

PMID- 25566365
TI  - Frequency of positive states of mind as a moderator of the effects of stress on
      psychological functioning and perceived health.
AB  - BACKGROUND: Emerging evidence indicates that individuals reporting more positive
      affect are healthier and live longer. The aim of this study was to examine if
      positive states of mind moderates the effect of perceived stress on psychological
      functioning and perceived health. METHODS: A cross-sectional sample, n = 382,
      responded to questions regarding perceived stress, depression, anxiety, perceived
      health, and frequency of positive states of mind. RESULTS: Using a series of
      regression analyses, the results confirmed a moderating role of positive states
      of mind on the association between perceived stress and psychological outcomes.
      CONCLUSIONS: Among people experiencing a high frequency of positive states of
      mind, perceived stress seems to have a low correspondence with depression,
      anxiety, and perceived health. But among those reporting a low frequency of
      positive states of mind, perceived stress was more strongly related and
      depression, anxiety, and perceived health suggesting a buffering effect of
      positive states of mind against the negative influence of stress.

PMID- 25566366
TI  - Life changes and depressive symptoms: the effects of valence and amount of
      change.
AB  - BACKGROUND: Only few studies have focused on the effects of positive life changes
      on depression, and the ones that did demonstrated inconsistent findings. The aim
      of the present study was to obtain a better understanding of the influence of
      positive life changes on depressive symptoms by decomposing life changes into a
      valence and an amount of change component. METHODS: Using hierarchical multiple
      regression, we examined the unique effects of valence
      (pleasantness/unpleasantness) and amount of change on depressive symptoms in 2230
      adolescents (M age: 16.28 years) from the TRAILS study. RESULTS: Adjusted for
      age, gender and pre-event depressive symptoms, the amount of life change was
      positively associated with depressive symptoms. A small excess of positive life
      changes predicted fewer symptoms, but experiencing a large excess of positive
      life changes did not have any additional beneficial effects, rather the opposite.
      Valence was more strongly associated with cognitive-affective than with
      neurovegetative-somatic symptoms. CONCLUSIONS: More positive life changes
      relative to negative life changes can protect against depressive symptoms, yet
      only when the amount of change is limited. This study encourages examination of
      the effects of life changes on specific symptom clusters instead of total numbers
      of depressive symptoms, which is the current standard.

PMID- 25566367
TI  - Culturally specific versus standard group cognitive behavioral therapy for
      smoking cessation among African Americans: an RCT protocol.
AB  - BACKGROUND: African American smokers experience disproportionately higher rates
      of tobacco-related illnesses compared to Caucasians. It has been suggested that
      interventions targeted to specific racial/ethnic groups (i.e., culturally
      specific) are needed; however, the literature examining the efficacy of
      culturally specific interventions is equivocal. Moreover, there are few
      descriptions of methods used to create these interventions. The main aim of this
      study is to test the efficacy of a culturally specific smoking cessation
      intervention among African Americans. METHODS/DESIGN: A 2-arm randomized
      controlled trial (RCT) will be conducted to assess the efficacy of a culturally
      specific group cognitive behavioral therapy (CBT), compared to standard group CBT
      among treatment-seeking smokers from the community. Participants in both
      conditions receive the transdermal nicotine patch (TNP) for 8-weeks. We intend to
      randomize at least 247 adult smokers who self-identify as African American into
      the trial. Enrolled participants are block randomized into one of two groups:
      Standard group CBT (control) or a culturally specific group CBT (CS-CBT). Groups
      are matched for time and attention, and consist of eight sessions. The primary
      outcome variable is 7-day point prevalence abstinence (7-day ppa). Smoking status
      is assessed at the end-of-counseling (EOC), and 3, 6, and 12-month follow-ups,
      with self-reported abstinence verified by saliva cotinine. We hypothesize that
      the CS-CBT condition will produce significantly greater smoking cessation rates
      compared to the control condition. We also expect that this effect will be
      moderated by acculturation and ethnic identity, such that the CS-CBT will show
      the greatest effect on cessation among participants who are less acculturated and
      have greater ethnic identity. DISCUSSION: Answering the fundamental question of
      whether culturally specific interventions lead to incremental efficacy over
      established, evidence-based approaches is of utmost importance. This study will
      have implications for the development and implementation of smoking cessation
      interventions among African Americans and other racial/ethnic minority groups.
      TRIAL REGISTRATION: NCT01811758.

PMID- 25566368
TI  - The impact of early life factors on cognitive function in old age: The Hordaland
      Health Study (HUSK).
AB  - BACKGROUND: Previous studies have shown that adverse conditions during fetal and
      early life are associated with lower performance on neurocognitive tests in
      childhood, adolescence and adult life. There is, however, a paucity in studies
      investigating these associations into old age. The aim was to investigate the
      impact of early life factors on cognitive function in old age by taking advantage
      of the potential for a linkage between a community survey and historical birth
      records. METHODS: A historical cohort study employing a linkage between a
      community survey of people aged 72-74 years with the participants' birth records
      (n=346). Early life factors included anthropometric measures taken at birth,
      birth complications, parental socioeconomic status, and maternal health status.
      The main outcome was a z-scored composite cognitive score, based on test scores
      from Kendrick Object Learning Test, Trail Making Test A, a modified version of
      the Digit Symbol Test, Block Design, a modified version of Mini-Mental State
      Examination and an abridged version of the Controlled Oral Word Association Test
      (COWAT). The separate cognitive tests were also individually analysed in relation
      to measures identified at birth. RESULTS: Higher parental socioeconomic status
      (SES; based on father's occupation) was associated with a higher value on the
      composite cognitive score (by 0.25 SD, p=0.0146) and higher Digit Symbol and
      Trail Making Test A performance. Higher head circumference at birth was
      associated with higher COWAT and Trail Making Test A performance. Both higher
      parental SES and head circumference at birth predicted cognitive function in old
      age independently of each other. There were no other consistent associations.
      CONCLUSIONS: In general we found little evidence for a substantial role of early
      life factors on late-life cognitive function. However, there was some evidence
      for an association with parental SES status and head circumference on certain
      cognitive domains.

PMID- 25566369
TI  - Cognitive behavioral therapy and mindfulness-based cognitive therapy for
      depressive symptoms in patients with diabetes: design of a randomized controlled
      trial.
AB  - BACKGROUND: Depressive symptoms are a common problem in patients with diabetes,
      laying an additional burden on both the patients and the health care system.
      Patients suffering from these symptoms rarely receive adequate evidence-based
      psychological help as part of routine clinical care. Offering brief evidence
      based treatments aimed at alleviating depressive symptoms could improve patients'
      medical and psychological outcomes. However, well-designed trials focusing on the
      effectiveness of psychological treatments for depressive symptoms in patients
      with diabetes are scarce. The Mood Enhancement Therapy Intervention Study (METIS)
      tests the effectiveness of two treatment protocols in patients with diabetes.
      Individually administered Cognitive Behavioral Therapy (CBT) and Mindfulness
      Based Cognitive Therapy (MBCT) are compared with a waiting list control condition
      in terms of their effectiveness in reducing the severity of depressive symptoms.
      Furthermore, we explore several potential moderators and mediators of change
      underlying treatment effectiveness, as well as the role of common factors and
      treatment integrity. METHODS/DESIGN: The METIS trial has a randomized controlled
      design with three arms, comparing CBT and MBCT with a waiting list control
      condition. Intervention groups receive treatment immediately; the waiting list
      control group receives treatment three months later. Both treatments are
      individually delivered in 8 sessions of 45 to 60 minutes by trained therapists.
      Primary outcome is severity of depressive symptoms. Anxiety, well-being, diabetes
      related distress, HbA1c levels, and intersession changes in mood are assessed as
      secondary outcomes. Assessments are held at pre-treatment, several time points
      during treatment, at post-treatment, and at 3-months and 9-months follow-up. The
      study has been approved by a medical ethical committee. DISCUSSION: Both CBT and
      MBCT are expected to help improve depressive symptoms in patients with diabetes.
      If MBCT is at least equally effective as CBT, MBCT can be established as an
      alternative approach to CBT for treating depressive symptoms in patients with
      diabetes. By analyzing moderators and mediators of change, more information can
      be gathered for whom and why CBT and MBCT are effective. TRIAL REGISTRATION:
      Clinical Trials NCT01630512.

PMID- 25566372
TI  - Report on personality and adherence to antibiotic therapy: a population-based
      study.
AB  - BACKGROUND: Antimicrobial resistance results from inappropriate use of
      antibiotics and makes common or life-threatening infections more difficult or
      sometimes impossible to treat. Proper adherence to antibiotic therapy is one
      among several measures required to prevent antimicrobial resistance. Knowledge of
      personality traits could help in identifying patients who need support with their
      adherence behaviour. Previous research has presented associations between
      personality traits and adherence to long-term medication treatment in individuals
      with different chronic diseases. However, there is limited knowledge about
      associations between personality traits and adherence to both antibiotic therapy
      and to shorter treatment periods. The aim was to explore the relation between
      personality and adherence behaviour in people prescribed antibiotics for common
      infections. METHODS: In a population-based study, 445 respondents reported on
      their prescribed antibiotic therapy and completed the Neuroticism, Extraversion,
      and Openness to experience Five-factor Inventory and the Medication Adherence
      Report Scale. Data were statistically analysed using descriptive statistics, t
      tests, bivariate correlations, multiple and logistic regressions. RESULTS: Non
      adherence was estimated to be 9.4%. The most common reasons for stopping therapy
      prematurely was that the respondent was now healthy and that the respondents
      experienced side-effects. Non-adherent respondents scored lower on the
      personality traits Agreeableness and Conscientiousness. A logistic regression
      showed that higher scores on Agreeableness decreased the risk for non-adherence
      to antibiotic therapy. In a multiple regression, Neuroticism was identified as a
      negative predictor, and both Agreeableness and Conscientiousness were identified
      as positive predictors of adherence behaviour. CONCLUSIONS: Preventive measures
      to decrease non-adherence may be to inform patients not to interrupt the
      antibiotic therapy when they start to feel healthy and to inform them about how
      to prevent and handle common side-effects. As associations between personality
      and adherence mainly have been described in relation to long-term treatments in
      chronic diseases, the current study add to the literature by showing that
      personality traits also seem to be reflected in adherence to shorter treatment
      periods with antibiotics for common infections. More studies in this specific
      area of adherence research are recommended.

PMID- 25566370
TI  - Evidence-based treatment for Depersonalisation-derealisation Disorder (DPRD).
AB  - BACKGROUND: Depersonalisation-derealisation disorder (DPRD) is a distressing and
      impairing condition with a pathophysiology that is not well understood.
      Nevertheless, given the growing interest in its pathogenesis, and the publication
      of a number of treatment trials, a systematic review of randomised controlled
      pharmacotherapy and psychotherapy trials is timely. METHODS: A systematic search
      of articles on DPRD published from January 1980 to August 2012, using Cochrane
      methods, was conducted. All randomised controlled trials (RCTs) of
      pharmacotherapy, psychotherapy, somatic interventions and a blend of these
      modalities for the treatment of depersonalisation disorder were included in the
      review. Searches were carried out on multiple databases. The bibliographies of
      all identified trials were checked for additional studies and authors were
      contacted for published trials. No unpublished trials were found and no
      restrictions were placed on language and setting. Data extraction sheets were
      further designed to enter specified data from each trial and risk of bias
      information was identified. PRISMA guidelines were also followed to ensure that
      our methodology and reporting were comprehensive. Of the unique 1296 papers that
      were retrieved, four studies met the inclusion criteria and were reviewed.
      RESULTS: Four RCTs (all within the duration of 12 weeks or less) met study
      criteria and were included (180 participants; age range 18-65 years). The four
      RCTs included two lamotrigine studies, one fluoxetine study and one biofeedback
      study. Evidence for the treatment efficacy of lamotrigine was found in one study
      (Cambridge Dissociation Scale, CDC: p < 0.001) with no evidence of effect for
      lamotrigine in the second study (CDS: p = 0.61 or Present State Examination: p =
      0.17). Fluoxetine and biofeedback were not more efficacious than the control
      condition, although there was a trend for fluoxetine to demonstrate greater
      efficacy in those with comorbid anxiety disorder. The four studies had 'low' or
      'unclear' risk of bias. CONCLUSION: The limited data from randomised controlled
      trials on the pharmacotherapy and psychotherapy of DPRD demonstrates inconsistent
      evidence for the efficacy of lamotrigine, and no efficacy for other
      interventions. Additional research on this disorder is needed.

PMID- 25566371
TI  - After a pair of self-control-intensive tasks, sucrose swishing improves
      subsequent working memory performance.
AB  - BACKGROUND: The limited strength model of self-control predicts that acts of self
      control impair subsequent performance on tasks that require self-control (i.e.,
      "ego depletion"), and the majority of the published research on this topic is
      supportive of this prediction. Additional research suggests that this effect can
      be alleviated by manipulating participants' motivation to perform-for instance,
      by having participants swish a drink containing carbohydrates, which is thought
      to function as a reward-or by requiring participants to complete two initial acts
      of self-control rather than only one. METHODS: Here, we explore both the effect
      of having participants perform two initial tasks thought to require self-control
      (versus two less self-control-intensive tasks) and the effect of swishing a drink
      containing sucrose (compared to control drinks) on subsequent self-control.
      Outcomes were analyzed using standard null hypothesis significance testing
      techniques (e.g., analysis of variance, t-tests). In some cases, test statistics
      were transformed into Bayes factors to aid in interpretation (i.e., to allow for
      acceptance of the null hypothesis). RESULTS: We found that performing two self
      control-intensive tasks actually improved subsequent self-control when
      participants swished a drink containing sucrose between tasks. For participants
      who swished control drinks, we found no evidence of ego depletion. CONCLUSIONS:
      We conclude that claims that self-control failure is caused by the depletion of a
      resource (or that it functions as if it relies on a limited resource) merit
      greater circumspection. Our results-all of which were either null or contrary to
      predictions from the limited strength model-are important for researchers
      interested in patterns of self-control failure.

PMID- 25566373
TI  - Validation and development of a shorter version of the resilience scale RS-11:
      results from the population-based KORA-age study.
AB  - BACKGROUND: The aim of this study was to assess reliability and validity of the
      Resilience Scale 11 (RS-11) and develop a shorter scale in a population-based
      study. METHODS: The RS-11 scale was administered to 3942 participants (aged 64 -
      94 years) of the KORA-Age study. To test reliability, factor analyses were
      carried out and internal consistency (Cronbach's alpha) was measured. Construct
      validity was measured by correlating scores with psychological constructs. The
      criterion for a shorter scale was a minimum internal consistency of .80. Shorter
      models were compared using confirmatory factor analysis. Sensitivity and
      specificity of RS-5 to RS-11 was analyzed. RESULTS: Factor analysis of the RS-11
      gave a 1-factor solution. Internal consistency was alpha = .86. A shorter version
      of the scale was developed with 5 items, which also gave a 1-factor solution and
      showed good validity. Internal consistency of this shorter scale: Resilience
      Scale 5 (RS-5) was alpha = .80. Sensitivity and specificity of RS-5 compared with
      RS-11 were .79 and .91 respectively. Both scales correlated significantly in
      expected directions with related constructs. CONCLUSIONS: The RS-11 and the RS-5
      are reliable, consistent and valid instruments to measure the ability of elderly
      individuals to successfully cope with change and misfortune.

PMID- 25566374
TI  - Listen protect connect for traumatized schoolchildren: a pilot study of
      psychological first aid.
AB  - BACKGROUND: Listen Protect Connect (LPC), a school-based program of Psychological
      First Aid delivered by non-mental health professionals, is intended to support
      trauma-exposed children. Our objective was to implement LPC in a school setting
      and assess the effectiveness of LPC on improving psychosocial outcomes associated
      with trauma. METHODS: A pilot quasi-experiment was conducted with middle school
      children self-identified or referred to the school nurse as potentially exposed
      to stressful life experiences. LPC was provided to students by the school nurse,
      and questionnaires were administered at baseline, 2-, 4- and 8-weeks to assess
      life stressors, symptoms of post-traumatic stress disorder and depression, social
      support, and school connectedness. A total of 71 measurements were collected from
      20 children in all. Although a small sample size, multiple measurements allowed
      for multivariable mixed effects models to analyze changes in the repeated
      outcomes over time. RESULTS: Students who received the intervention had reduced
      depressive and posttraumatic stress symptoms from baseline throughout follow-up
      period. Total social support also increased significantly from baseline through 8
      weeks, and school connectedness increased up to 4-weeks post-intervention.
      CONCLUSIONS: This study demonstrates the potential of LPC as a school-based
      intervention of Psychological First Aid. Future randomized trials of LPC are
      needed, however.

PMID- 25566375
TI  - Exploring relationships over time between psychological distress, perceived
      stress, life events and immature defense style on disordered eating pathology.
AB  - BACKGROUND: Perceived stress, immature defense style, depression and anxiety and
      negative life events all are known to be associated with eating disorders. The
      present study aimed to investigate the relationships between these factors and
      their relative strength of association with eating disorder symptoms over time.
      METHODS: This research was embedded in a longitudinal study of adult women with
      varying levels of eating disorder symptoms and who were initially recruited from
      tertiary educational institutions in two Australian states. Four years from
      initial recruitment, 371 participants completed the Eating Disorder Examination-
      Questionnaire (EDE-Q) for eating disorder symptoms. Kessler-10 Psychological
      Distress Scale (K-10) as a measure of depression and anxiety, a Life Events
      Checklist as a measure of previous exposure to potentially traumatic events, the
      Defense Style Questionnaire (DSQ) and the Perceived Stress Scale (PSS) to
      determine perceived stress. One year later, in year 5, 295 (878.7%) completed
      follow-up assessments including the EDE-Q. The questionnaires were completed
      online or returned via reply paid post. RESULTS: All four independent factors
      were found to correlate significantly with the global EDE-Q score in cross
      sectional analyses (all Spearman rho (rs) >0.18, p < 0.01) and at one year follow
      up (all rs > 0.15, all p < 0.05). In multivariate linear regression modeling
      adjusted for age and year 4 global EDE-Q scores, perceived stress and
      psychological distress scores were significantly associated with year 5 global
      EDE-Q scores (p = 0.046 and <0.001 respectively). CONCLUSIONS: Psychological
      distress, and to a lesser degree perceived stress had the strongest association
      with eating disorder symptoms over time The findings support further
      investigation of interventions to reduce distress and perceived stress in adult
      females with disordered eating.

PMID- 25566376
TI  - Can theory of mind deficits be measured reliably in people with mild and moderate
      Alzheimer's dementia?
AB  - BACKGROUND: Patients suffering from Alzheimer's dementia develop difficulties in
      social functioning. This has led to an interest in the study of "theory of mind"
      in this population. However, difficulty has arisen because the associated
      cognitive demands of traditional short story theory of mind assessments result in
      failure per se in this population, making it challenging to test pure theory of
      mind ability. METHODS: Simplified, traditional 1st and 2nd order theory of mind
      short story tasks and a battery of alternative theory of mind cartoon jokes and
      control slapstick cartoon jokes, without memory components, were administered to
      16 participants with mild-moderate Alzheimer's dementia, and 11 age-matched
      healthy controls. RESULTS: No significant differences were detected between
      participants with Alzheimer's dementia and controls on the 1st or 2nd order
      traditional short story theory of mind tasks (p = 0.155 and p = 0.154
      respectively). However, in the cartoon joke tasks there were significant
      differences in performance between the Alzheimer participants and the control
      group, this was evident for both theory of mind cartoons and the control
      'slapstick' jokes. CONCLUSION: It remains very difficult to assess theory of mind
      as an isolated phenomenon in populations with global cognitive impairment, such
      as Alzheimer's dementia, as the tasks used to assess this cognition invariably
      depend on other cognitive functions. Although a limitation of this study is the
      small sample size, the results suggest that there is no measurable specific
      theory of mind deficit in people with Alzheimer's dementia, and that the use of
      theory of mind representational models to measure social cognitive ability may
      not be appropriate in this population.

PMID- 25566377
TI  - Determinants of variability in motor performance in middle childhood: a cross
      sectional study of balance and motor co-ordination skills.
AB  - BACKGROUND: Physical activity is a key component of exploration and development.
      Poor motor proficiency, by limiting participation in physical and social
      activities, can therefore contribute to poor psychological and social
      development. The current study examined the correlates of motor performance in a
      setting where no locally validated measures of motor skills previously existed.
      The development of an appropriate assessment schedule is important to avoid the
      potential misclassification of children's motor performance. METHODS: A cross
      sectional study was conducted among a predominantly rural population. Boys (N =
      148) and girls (N = 160) aged between 8 and 11 years were randomly selected from
      five schools within Kilifi District in Kenya. Four tests of static and dynamic
      balance and four tests of motor coordination and manual dexterity were developed
      through a 4-step systematic adaptation procedure. Independent samples t-tests,
      correlational, univariate and regression analyses were applied to examine
      associations between background variables and motor scores. RESULTS: The battery
      of tests demonstrated acceptable reliability and validity. Variability in motor
      performance was significantly associated with a number of background
      characteristics measured at the child, (gender, nutritional status and school
      exposure) household (household resources) and neighbourhood levels (area of
      residence). The strongest effect sizes were related to nutritional status and
      school exposure. CONCLUSIONS: The current study provides preliminary evidence of
      motor performance from a typically developing rural population within an age
      range that has not been previously studied. As well as being culturally
      appropriate, the developed tests were reliable, valid and sensitive to biological
      and environmental correlates. Further, the use of composite scores seems to
      strengthen the magnitude of differences seen among groups.

PMID- 25566378
TI  - Clinical utility of the cogstate brief battery in identifying cognitive
      impairment in mild cognitive impairment and Alzheimer's disease.
AB  - BACKGROUND: Previous studies have demonstrated the utility and sensitivity of the
      CogState Brief Battery (CBB) in detecting cognitive impairment in Alzheimer's
      disease (AD) and mild cognitive impairment (MCI) and in assessing cognitive
      changes in the preclinical stages of AD. Thus, the CBB may be a useful screening
      tool to assist in the management of cognitive function in clinical settings. In
      this study, we aimed to determine the utility of the CBB in identifying the
      nature and magnitude of cognitive impairments in MCI and AD. METHODS: Healthy
      adults (n = 653) adults with amnestic MCI (n = 107), and adults with AD (n = 44)
      who completed the CBB participated in this study. Composite Psychomotor/Attention
      and Learning/Working Memory scores were computed from the individual CBB tests.
      Differences in composite scores were then examined between the three groups; and
      sensitivity and specificity analyses were conducted to determine cut scores for
      the composite scores that were optimal in identifying MCI- and AD-related
      cognitive impairment. RESULTS: Large magnitude impairments in MCI (g = 2.2) and
      AD (g = 3.3) were identified for the learning/working memory composite, and
      smaller impairments were observed for the attention/psychomotor composite (g's =
      0.5 and 1, respectively). The cut-score associated with optimal sensitivity and
      specificity in identifying MCI-related cognitive impairment on the
      learning/working memory composite was -1SD, and in the AD group, this optimal
      value was -1.7SD. Both composite scores showed high test-retest reliability (r =
      0.95) over four months. Poorer performance on the memory composite was also
      associated with worse performance on the Mini Mental State Exam and increasing
      severity on the Clinical Dementia Rating Scale sum of boxes score. CONCLUSIONS:
      Results of this study suggest that the CogState learning/working memory composite
      score is reduced significantly in CI and AD, correlate well with measures of
      disease classification and are useful in identifying memory impairment related to
      MCI- and AD.

PMID- 25566379
TI  - Promoting psychosocial wellbeing following stroke using narratives and guided
      self-determination: a feasibility study.
AB  - BACKGROUND: Extensive studies have documented the complex and comprehensive
      psychosocial consequences of stroke. Psychosocial difficulties significantly
      affect long-term functioning and quality of life. Many studies have explored
      psychosocial interventions to prevent or treat psychosocial problems, but most
      have found modest effects. This study evaluated, from the perspective of adult
      stroke survivors, (1) the content, structure and process and (2) experienced
      usefulness of a dialogue-based psychosocial nursing intervention in primary care
      aimed at promoting psychosocial health and wellbeing. METHODS: This was part of a
      feasibility study guided by the UK MRC complex interventions framework. It
      consisted of dialogue-based encounters with trained health professionals during
      approximately the first year poststroke. It was tested in two formats; individual
      or group encounters. Inclusion criteria were: Acute stroke, above 18 y.o.,
      sufficient physical and cognitive functioning to participate. Data were collected
      immediately before, during and 14 days after the completion of the intervention.
      Pre- and post-data included medical and demographic data, quality of life,
      emotional wellbeing, life satisfaction, anxiety and depression. Qualitative
      interviews focusing on participant experiences were conducted two weeks following
      the intervention. Log notes taken by the health professionals conducting the
      intervention and work sheets filled in by participants also comprised data. Data
      analysis was case-oriented. The structured instruments were analysed regarding
      completeness of data and indication of changes in outcome variables. The
      qualitative interviews, log notes and work sheets were analysed using thematic
      content analysis. RESULTS: Twenty-five stroke survivors (17 men, 8 women), median
      age 64 (range 33-89), participated. Physical limitations varied from mild to
      severe. Seven participants had moderate to severe expressive aphasia. The
      participants found the content and process of the intervention relevant. Both the
      individual and group formats were found useful. Patients with aphasia reported
      that there were too few encounters (eight encounters were originally planned).
      The participants underscored the benefits of being supported through a difficult
      time, having a chance to tell and (re)create their story and being supported in
      their attempts to cope with the situation. CONCLUSIONS: This study provides
      initial support for the usefulness of the psychosocial intervention and
      highlights areas requiring further consideration and development. TRIAL
      REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01912014.

PMID- 25566381
TI  - An association of adult personality with prenatal and early postnatal growth: the
      EPQ lie-scale.
AB  - BACKGROUND: Recent studies have noted differences in social acquiescence and
      interpersonal relations among adults born preterm or with very low birth weight
      compared to full term adults. In addition, birth weight has been observed to be
      negatively correlated with lie-scale scores in two studies. We attempted to
      replicate and extend these studies by examining young adult lie-scale scores in a
      Danish birth cohort. METHOD: Weight, length and head circumference of 9125
      children from the Copenhagen Perinatal Cohort were measured at birth and at 1, 3
      and 6 years. A subsample comprising 1182 individuals participated in a follow-up
      at 20-34 years and was administered the Eysenck Personality Questionnaire (EPQ)
      which includes a lie-scale (indicating social acquiescence or self-insight).
      Associations between lie-scale scores and weight, length and head circumference
      respectively were analysed by multiple linear regression adjusting for single
      mother status, parity, mother's age, father's age, parental social status, age at
      EPQ measurement, intelligence, and adult size. RESULTS: Male infants with lower
      weight, length, and head-circumference at birth and the following three years
      grew up to have higher scores on the lie-scale as young adults. Most of these
      associations remained significant after adjustment for the included covariates.
      No associations were found for females. Analyses were also conducted with
      neuroticism, extraversion and psychoticism as outcome variables, but no
      significant associations were found for these traits after adjustment.
      CONCLUSIONS: The findings replicate and extend findings from previous studies
      suggesting that size at birth and during the first three years of life is
      significantly associated with social acquiescence in adult men. They highlight
      the potential influence of prenatal and early postnatal development on
      personality growth and development.

PMID- 25566382
TI  - The effects of the prevention program 'New Perspectives' (NP) on juvenile
      delinquency and other life domains: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: New Perspectives (NP) is a prevention program aiming to prevent that
      youth at onset of a criminal career will develop a persistent criminal behaviour
      pattern. The effects of NP on juvenile delinquency and other life domains are
      investigated, using a randomized controlled trial (RCT). METHOD/DESIGN: In the
      present study at-risk youth aged 12 to 23 years are assigned randomly to the
      intervention (N = 90, NP) or control condition consisting of care as usual (N =
      90, CAU). After screening, random assignment, and consent to participate,
      adolescents and their parents are requested to complete questionnaires. Data are
      collected at four points in time: at baseline (before the start of the
      intervention), after 3 months, after 6 months (post-test) and 1 year after
      treatment (follow-up). Primary outcome measures include involvement in delinquent
      behaviour and recidivism. Secondary outcome measures include parenting behaviour,
      life events, prosocial behaviour, deviant and prosocial peers, externalizing
      behaviour, cognitive distortions, moral reasoning, self-worth, anxiety,
      depression, client satisfaction, therapeutic alliance and motivation.
      Standardized questionnaires and interviews are used to collect data. Moderator
      analyses will also be conducted in order to examine the influence of ethnic
      background, gender and age on the program effectiveness. DISCUSSION: The present
      study will provide new insights in the effects of a prevention program targeting
      youth at risk for the development of a persistent criminal career. TRIAL
      REGISTRATION: Dutch trial register number NTR4370. The study is financially
      supported by a grant from ZonMw, the Dutch Organization for Health research and
      Development, grant number 157004006. The study is approved by the Ethics
      Committee of the University of Amsterdam, approval number 2011-CDE-01.

PMID- 25566380
TI  - The association between social capital and mental health and behavioural problems
      in children and adolescents: an integrative systematic review.
AB  - BACKGROUND: Mental health is an important component of overall health and
      wellbeing and crucial for a happy and meaningful life. The prevalence of mental
      health problems amongst children and adolescent is high; with estimates
      suggesting 10-20% suffer from mental health problems at any given time. These
      mental health problems include internalising (e.g. depression and social anxiety)
      and externalising behavioural problems (e.g. aggression and anti-social
      behaviour). Although social capital has been shown to be associated with mental
      health/behavioural problems in young people, attempts to consolidate the evidence
      in the form of a review have been limited. This integrative systematic review
      identified and synthesised international research findings on the role and impact
      of family and community social capital on mental health/behavioural problems in
      children and adolescents to provide a consolidated evidence base to inform future
      research and policy development. METHODS: Nine electronic databases were searched
      for relevant studies and this was followed by hand searching. Identified
      literature was screened using review-specific inclusion/exclusion criteria, the
      data were extracted from the included studies and study quality was assessed.
      Heterogeneity in study design and outcomes precluded meta-analysis/meta
      synthesis, the results are therefore presented in narrative form. RESULTS: After
      screening, 55 studies were retained. The majority were cross-sectional surveys
      and were conducted in North America (n = 33); seven were conducted in the UK.
      Samples ranged in size from 29 to 98,340. The synthesised results demonstrate
      that family and community social capital are associated with mental
      health/behavioural problems in children and adolescents. Positive parent-child
      relations, extended family support, social support networks, religiosity,
      neighbourhood and school quality appear to be particularly important.
      CONCLUSIONS: To date, this is the most comprehensive review of the evidence on
      the relationships that exist between social capital and mental health/behavioural
      problems in children and adolescents. It suggests that social capital generated
      and mobilised at the family and community level can influence mental
      health/problem behaviour outcomes in young people. In addition, it highlights key
      gaps in knowledge where future research could further illuminate the mechanisms
      through which social capital works to influence health and wellbeing and thus
      inform policy development.

PMID- 25566384
TI  - Cluster-randomised controlled trial of an occupational therapy group intervention
      for children designed to promote emotional wellbeing: study protocol.
AB  - BACKGROUND: Symptoms of anxiety and depression are common in childhood, as are
      risk factors that undermine wellbeing: low self-esteem and limited participation
      in daily occupations. Current treatments focus primarily on modifying internal
      cognitions with insufficient effect on functional outcomes. Occupational
      therapists have a role in measuring and enabling children's functional abilities
      to promote health and wellbeing. To-date there is no evidence for the use of
      occupational therapy as an intervention to promote mental health or increase self
      esteem, participation and wellbeing in a preventative context. The aim of this
      cluster-randomised controlled study is to investigate the effectiveness of an 8
      week occupational therapy group intervention (Kia Piki te Hauora) at reducing
      symptoms of anxiety and depression and improving self-esteem, participation and
      wellbeing in children aged 11-13 years. METHODS/DESIGN: In this two-arm,
      pragmatic, cluster-randomised controlled trial, 154 children will be recruited
      from 14 schools. All mainstream schools in the region will be eligible and a
      convenience sample of 14 schools, stratified by decile ranking (i.e. low, medium,
      and high) will be recruited. Eight to twelve students aged 11-13 years from each
      school will be recruited by senior school personnel. Following consent, schools
      will be randomised to either the intervention or waitlist control arm of the
      trial. The study will employ a parallel and one-way waitlist-to-intervention
      crossover design. Each cluster's involvement will last up to 19 or 31 weeks
      depending on allocation to the intervention or waitlist respectively. The primary
      outcome is symptoms of anxiety and secondary outcomes are symptoms of depression,
      self-esteem, participation in daily occupations and wellbeing. Outcome
      measurement will be repeated at baseline, post-intervention and again at 8-9
      weeks follow-up. Planned statistical analyses will utilise repeated measures
      analysis of covariance. The primary analysis will be based on an intention-to
      treat analysis set and include only parallel data. The crossover data will only
      be used in secondary analyses. DISCUSSION: This is the first cluster-randomised
      controlled trial to investigate an occupational therapy intervention promoting
      emotional wellbeing in a non-clinical sample of children. Results will contribute
      to the limited evidence base for occupational therapists in this field and
      potentially support investment in these services. TRIAL REGISTRATION:
      Australia/New Zealand Clinical Trials Register: ACTRN12614000453684.

PMID- 25566383
TI  - Design of a comparative effectiveness evaluation of a culturally tailored versus
      standard community-based smoking cessation treatment program for LGBT smokers.
AB  - BACKGROUND: Smoking prevalence rates among the lesbian, gay, bisexual, and
      transgender (LGBT) population are significantly higher than the general
      population. However, there is limited research on smoking cessation treatments in
      this group, particularly on culturally targeted interventions. Moreover, there
      are few interventions that address culturally specific psychosocial variables
      (e.g., minority stress) that may influence outcomes. This paper describes the
      protocol for a comparative effectiveness trial testing an evidence-based smoking
      cessation program, Courage to Quit, against a culturally tailored version for
      LGBT smokers, and examines the role of culturally specific psychosocial variables
      on cessation outcomes. METHODS/DESIGN: To examine the effectiveness of a
      culturally targeted versus standard smoking cessation intervention, the study
      utilizes a 2-arm block, randomized, control trial (RCT) design. Adult LGBT
      participants (n = 400) are randomized to one of the two programs each consisting
      of a six-session group program delivered in a community center and an eight week
      supply of the transdermal nicotine patch. Four individualized telephone
      counseling sessions occur at weeks 2, 5, 7, and 9, at times of greatest risk for
      relapse. Study outcome measures are collected at baseline, and 1, 3, 6, and 12
      months post quit date. Primary outcomes are expired air carbon monoxide verified
      7-day point-prevalence quit rates at each measurement period. Secondary outcomes
      assess changes in cravings, withdrawal symptoms, smoking cessation self-efficacy,
      and treatment adherence. Additionally, study staff examines the role of
      culturally specific psychosocial variables on cessation outcomes using path
      analysis. DISCUSSION: Determining the efficacy of culturally specific versus
      standard evidence based approaches to smoking cessation is a critical issue
      facing the field today. This study provides a model for the development and
      implementation of a culturally tailored smoking cessation intervention for LGBT
      participants and addresses a gap in the field by examining the role of culturally
      psychosocial variables associated with cessation outcomes. TRIAL REGISTRATION:
      U.S. National Institutes of Health Clinical Trials NCT01633567 Registered 30 May
      2012.

PMID- 25566385
TI  - Improving psychosocial health and employment outcomes for individuals receiving
      methadone treatment: a realist synthesis of what makes interventions work.
AB  - BACKGROUND: For over 50 years, methadone has been prescribed to opioid-dependent
      individuals as a pharmacological approach for alleviating the symptoms of opioid
      withdrawal. However, individuals prescribed methadone sometimes require
      additional interventions (e.g., counseling) to further improve their health. This
      study undertook a realist synthesis of evaluations of interventions aimed at
      improving the psychosocial and employment outcomes of individuals on methadone
      treatment, to determine what interventions work (or not) and why. METHODS: The
      realist synthesis method was utilized because it uncovers the processes (or
      mechanisms) that lead to particular outcomes, and the contexts within which this
      occurs. A comprehensive search process resulted in 31 articles for review. Data
      were extracted from the articles, and placed in four templates to assist with
      analysis. Data analysis was an iterative process and involved comparing and
      contrasting data within and across each template, and cross checking with
      original articles to determine key patterns in the data. RESULTS: For individuals
      on methadone, engagement with an intervention appears to be important for
      improved psychosocial and/or employment outcomes. The engagement process involves
      attendance at interventions as well as an investment in what is offered. Three
      intervention contexts (often in some combination) support the engagement process:
      a) client-centered contexts (or those where clients' psychosocial and/or
      employment needs/issues/skills are recognized and/or addressed); b) contexts
      which address clients' socio-economic conditions and needs; and, c) contexts
      where there are positive client-counselor and/or peer relationships. There is
      some evidence that sometimes ongoing engagement is necessary to maintain positive
      outcomes. There is also some evidence that complete abstinence from drugs (e.g.,
      cocaine, heroin) is not necessary for engagement. CONCLUSIONS: It is important to
      consider how the contexts of interventions might elicit and/or support clients'
      engagement. Further research is needed to explore how an individual's background
      (e.g., involvement with different interventions over an extended period) may
      influence engagement. Long-term engagement may be necessary to sustain some
      positive outcomes although how long is unclear and requires further research.
      Engagement can occur without complete abstinence from such drugs as cocaine or
      heroin, but additional research is required as engagement may be influenced by
      the extent and type of drug use.

PMID- 25566386
TI  - Long shadows: a prospective study of predictors of relationship dissolution over
      17 child-rearing years.
AB  - BACKGROUND: Parental relationship dissolutions have repeatedly been linked to
      negative outcomes for children, but predictors of parental dissolutions have been
      far less studied. Knowledge about parental dissolutions occurring after the early
      years of parenthood is especially sparse. The aim of the current study was to
      investigate whether a broad set of predictors from families of toddlers were
      associated with relationship dissolutions throughout the next 17 years of
      parenthood. We specifically investigated whether different predictors were
      associated with short and long term dissolutions; and whether associations with
      long term dissolutions were mediated by relationship dissatisfaction or child
      rearing conflicts. METHODS: Questionnaire data from 500 married or cohabiting
      mothers participating in a longitudinal population based study, the Norwegian
      TOPP study, was used. Child related strains, positive and negative aspects of
      relationship quality, and other intrinsic, environmental, and socio-demographic
      factors were assessed when children were 18 months old. Associations between
      early predictors and early dissolution (before children were 8 years old) and
      late dissolutions (when children were between 8 and 19 years) were compared using
      multinomial logistic regression analyses. Indirect paths from early predictors
      through relationship satisfaction and child-rearing conflicts to late
      dissolutions were investigated among couples that were still intact when children
      were 8 years old. RESULTS: Expression of criticism and most socio-demographic
      variables were associated with early dissolutions only, while temperamental
      sociability and child related strains were associated with long term dissolutions
      only in the adjusted regression models. Low levels of emotional support predicted
      both early and late dissolutions. Associations from low emotional support and
      child related strains to long term dissolutions were mediated by relationship
      dissatisfaction, indicating that cascades towards dissolutions may originate in
      these early predictors. No indirect paths were identified from early predictors
      through child-rearing conflicts, indicating that low levels of positivity, rather
      than high conflict levels, are associated with dissolutions in long-term
      relationships. CONCLUSIONS: Predictors of dissolutions over the next 17 years
      could be identified among mothers of toddlers. Different predictors were
      associated with early and late dissolutions, indicating different cascades.

PMID- 25566388
TI  - Direct and indirect aggression and victimization in adolescents - associations
      with the development of psychological difficulties.
AB  - BACKGROUND: Previous research has established that direct and indirect forms of
      aggression differ in their association with gender and type of psychological
      difficulties. One purpose of the present study was to test if the same applies to
      direct and indirect victimization. A second purpose was to study these
      associations not only cross-sectionally (as in most previous research) but also
      longitudinally. A third purpose was to test the hypotheses that there are
      prospective bidirectional associations not only between victimization and
      psychological difficulties (which has been shown in previous research), but also
      between aggression and psychological difficulties, and that direct and indirect
      forms of aggression and victimization show different associations with different
      types of psychological difficulties. METHODS: The participants were a community
      sample of all students in two grades of regular school in a Swedish municipality
      who answered questionnaires as part of a two-wave longitudinal study with a one
      year interval. The participants were 13-15 years old, and there were longitudinal
      data on 893 students, which represented 85% of all students. The cross-sectional
      associations were primarily tested by semi-partial correlations, and the
      longitudinal associations by hierarchical multiple regression. RESULTS: The
      results corroborated the meaningfulness of differentiating not only between
      direct and indirect aggression but also between direct and indirect
      victimization. Boys reported being more victim to direct aggression, whereas
      girls reported being more victim to indirect aggression. Direct aggression
      predicted increased conduct problems in boys, whereas indirect aggression
      predicted increased conduct problems in girls, and conduct problems reciprocally
      predicted increased direct and indirect aggression. Indirect victimization showed
      prospective bidirectional associations with emotional symptoms and conduct
      problems, suggesting the potential development of vicious cycles of escalating
      problems in these areas. CONCLUSIONS: The present results indicate that direct
      and indirect aggression, as well as direct and indirect victimization, may have
      different roles in the development of psychological difficulties in young
      adolescents. Further, the demonstration of prospective bidirectional associations
      points to a possible mechanism for the development of psychological difficulties,
      that may be described in terms of dynamical systems theory. This has potential
      relevance both for the prevention and the treatment of psychopathology.

PMID- 25566387
TI  - A randomized controlled trial of cognitive remediation and d-cycloserine for
      individuals with bipolar disorder.
AB  - BACKGROUND: Cognitive remediation (CR) has shown significant promise in
      addressing the cognitive deficits that accompany serious mental illness. However,
      this intervention does not appear to completely ameliorate the cognitive deficits
      that accompany these illnesses. D-cycloserine (DCS), an NMDA receptor partial
      agonist, has been shown to enhance the therapeutic benefits of learning-based
      psychosocial interventions for psychiatric disorders. Thus, the goal of this
      study is to examine the utility of combining cognitive remediation and d
      cycloserine in the treatment of cognitive deficits among individuals with bipolar
      disorder. METHODS/DESIGN: Approximately forty individuals with bipolar disorder
      will be recruited to participate in this study. Participants will be randomized
      to one of two study arms: CR + DCS or CR + placebo. The primary outcome for this
      study is change in cognitive functioning. We will also examine several secondary
      outcomes, including the rate of change of cognitive functioning, social
      functioning, and symptomatology. DISCUSSION: Cognitive deficits are a rate
      limiting factor in functional recovery among individuals with bipolar disorder.
      Unfortunately, treatment options for these deficits are limited. The results of
      the proposed study may reveal a valuable intervention strategy (i.e., CR with
      concurrent DCS) to improve cognitive functioning among individuals with bipolar
      disorder. Ultimately, this treatment strategy may prove useful in addressing the
      cognitive deficits that are ubiquitous across serious mental illnesses. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01934972.

PMID- 25566389
TI  - Associations between social isolation, pro-social behaviour and emotional
      development in preschool aged children: a population based survey of kindergarten
      staff.
AB  - BACKGROUND: The impact of peer relationships has been extensively reported during
      adolescence, when peer influence is generally considered to be at its greatest.
      Research on social isolation during childhood has found associations with school
      achievement, future relationships and adult mental health. Much of the evidence
      is derived from either parent or child-rated assessment of peer relationships,
      each of which have their limitations. METHODS: We report findings from Goodman's
      Strengths and Difficulties Questionnaire (SDQ), completed by staff in preschool
      establishments for over 10,000 children in their preschool year (aged 4-5),
      linked with routine demographic data. Correlations between scores and
      demographics were explored. Regression models examined the independent
      relationships between three social isolation variables, taken from the SDQ Peer
      Relationship Problems, Pro-social Behaviour and Emotional Symptoms subscales,
      controlling for demographics. RESULTS: There were substantial overlaps between
      problem scores. Regression models found all social isolation variables to be
      significantly correlated with social and emotional functioning. Different types
      of social isolation appeared to relate to different psychological domains, with
      unpopularity having a stronger relationship with poor pro-social skills, whereas
      being solitary was more strongly linked to poorer emotional functioning.
      CONCLUSIONS: Social isolation does have a significant association with reported
      child social and emotional difficulties, independent of demographic
      characteristics. The analysis highlights the complexity of measuring social
      isolation in young children. Different types of social isolation were found to
      have relationships with specific areas of social and emotional functioning.

PMID- 25566390
TI  - Exploring salivary cortisol and recurrent pain in mid-adolescents living in two
      homes.
AB  - BACKGROUND: Each year, around 50.000 children in Sweden experience a separation
      between their parents. Joint physical custody (JPC), where the child alternates
      homes between the parents for about equal amount of time, has become a common
      living arrangement after parental separation. Children in two homes could benefit
      from everyday contact with both parents and access to both parents' financial
      resources. However, children could experience stress from being constantly moving
      and potentially exposed to parental conflicts. Still, studies on JPC and
      biological functioning related to stress, are lacking. The aim of this study was
      to investigate how living arrangements (intact family/JPC) relate to HPA-axis
      activity and recurrent pain in mid-adolescents. METHODS: Mid-adolescents (106
      girls and 51 boys) provided demographic details, self-reports of recurrent pain
      (headache, stomachache, neck/shoulder and back pain) and salivary samples.
      Salivary cortisol samples were collected: 1) immediately at awakening, 2) +30
      minutes, 3) +60 minutes, and 4) at 8 p.m. The cortisol awakening response (CAR)
      was computed using an established formula. Additionally, the diurnal decline
      between the waking and 8 p.m. samples was computed. RESULTS: Hierarchical
      multiple regressions showed that living arrangements (intact family/JPC) was not
      associated with morning cortisol (CAR), the diurnal cortisol decline or with
      recurrent pain. However, sex was a significant predictor of both cortisol
      measures and recurrent pain with girls exhibiting a higher cortisol awakening
      response and a greater diurnal decline value as well as reporting more recurrent
      pain than did boys. CONCLUSIONS: Living arrangements were not associated with HPA
      axis activity or recurrent pain in this group of well-functioning mid
      adolescents. Although this study is the first to investigate how living
      arrangements relate to HPA-axis functioning and additional studies are needed,
      the tentative findings suggest that these mid-adolescents have adapted to their
      living arrangements and that other factors play a more pertinent role for HPA
      functioning and subjective health.

PMID- 25566392
TI  - Psychometric evaluation of the Swedish version of the pure procrastination scale,
      the irrational procrastination scale, and the susceptibility to temptation scale
      in a clinical population.
AB  - BACKGROUND: Procrastination is a prevalent self-regulatory failure associated
      with stress and anxiety, decreased well-being, and poorer performance in school
      as well as work. One-fifth of the adult population and half of the student
      population describe themselves as chronic and severe procrastinators. However,
      despite the fact that it can become a debilitating condition, valid and reliable
      self-report measures for assessing the occurrence and severity of procrastination
      are lacking, particularly for use in a clinical context. The current study
      explored the usefulness of the Swedish version of three Internet-administered
      self-report measures for evaluating procrastination; the Pure Procrastination
      Scale, the Irrational Procrastination Scale, and the Susceptibility to Temptation
      Scale, all having good psychometric properties in English. METHODS: In total, 710
      participants were recruited for a clinical trial of Internet-based cognitive
      behavior therapy for procrastination. All of the participants completed the
      scales as well as self-report measures of depression, anxiety, and quality of
      life. Principal Component Analysis was performed to assess the factor validity of
      the scales, and internal consistency and correlations between the scales were
      also determined. Intraclass Correlation Coefficient, Minimal Detectable Change,
      and Standard Error of Measurement were calculated for the Irrational
      Procrastination Scale. RESULTS: The Swedish version of the scales have a similar
      factor structure as the English version, generated good internal consistencies,
      with Cronbach's alpha ranging between .76 to .87, and were moderately to highly
      intercorrelated. The Irrational Procrastination Scale had an Intraclass
      Correlation Coefficient of .83, indicating excellent reliability. Furthermore,
      Standard Error of Measurement was 1.61, and Minimal Detectable Change was 4.47,
      suggesting that a change of almost five points on the scale is necessary to
      determine a reliable change in self-reported procrastination severity.
      CONCLUSIONS: The current study revealed that the Pure Procrastination Scale, the
      Irrational Procrastination Scale, and the Susceptibility to Temptation Scale are
      both valid and reliable from a psychometric perspective, and that they might be
      used for assessing the occurrence and severity of procrastination via the
      Internet. TRIAL REGISTRATION: The current study is part of a clinical trial
      assessing the efficacy of Internet-based cognitive behavior therapy for
      procrastination, and was registered 04/22/2013 on ClinicalTrials.gov
      (NCT01842945).

PMID- 25566391
TI  - Comparative effectiveness of cognitive and dynamic therapies for major depressive
      disorder in a community mental health setting: study protocol for a randomized
      non-inferiority trial.
AB  - BACKGROUND: There is substantial evidence that cognitive therapy is an effective
      intervention for the treatment of major depressive disorder. Although dynamic
      psychotherapies have been widely studied and are commonly practiced worldwide,
      there are few randomized comparisons of cognitive therapy and dynamic therapy for
      major depressive disorder. METHODS: We are completing data collection on a
      randomized non-inferiority trial comparing the effectiveness of cognitive therapy
      and short-term dynamic psychotherapy in the treatment of major depressive
      disorder in the community mental health setting. Therapists employed in the
      community setting have been recruited for training in either short-term dynamic
      psychotherapy or cognitive therapy. Patients seeking services at the community
      site who meet criteria for major depressive disorder based on a blind independent
      diagnostic interview are randomized to 16 sessions of treatment. All patients are
      assessed at baseline and months 1, 2, 4, and 5 utilizing a comprehensive battery.
      DISCUSSION: This study adds to the growing literature evaluating the
      effectiveness of short-term dynamic psychotherapy for specific diagnostic groups.
      These results will have implications for the dissemination of effective
      interventions for major depressive disorder in community mental health settings.
      TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, a service of
      the United States National Institute of Health. NIH Identifier: NCT01207271.
      Registered 21 September 2010.

PMID- 25566393
TI  - Protothecal peritonitis in child after bone marrow transplantation: case report
      and literature review of paediatric cases.
AB  - The case presented here illustrates a protothecal infection caused by Prototheca
      wickerhamii in a paediatric haematopoietic stem cell recipient followed by a
      review of the literature of all 13 paediatric cases published since 1980.
      Protothecosis is a rare disease caused by algae, not described in this setting
      before. Infection was proven additionally post-mortem from peritoneal dialysis
      fluid. Even though no death of a paediatric patient due to this infection has
      been reported and the mortality rate associated with protothecosis is low, our
      patient died from multiorgan failure as a result of numerous post-transplant
      complications and a strain of cultivated alga that was highly resistant to
      antifungal agents. Prototheca spp. show various susceptibility profiles, and
      there is no direct correlation between in vitro activity and clinical response.
      There are different treatment regimens described but there are no clear published
      guidelines of specific therapy of protothecosis. Paediatric cases were
      successfully treated mostly with amphotericin B and azoles. As the number of
      immunocompromised patients increases, it is necessary to think more about unusual
      pathogens such as Prototheca. 

PMID- 25566394
TI  - Genomic analysis of three African strains of Bacillus anthracis demonstrates that
      they are part of the clonal expansion of an exclusively pathogenic bacterium.
AB  - Bacillus anthracis is the causative agent of anthrax and is classified as a
      'Category A' biological weapon. Six complete genomes of B. anthracis (A0248,
      Ames, Ames Ancestor, CDC684, H0491, and Sterne) are currently available. In this
      report, we add three African strain genomes: Sen2Col2, Sen3 and Gmb1. To study
      the pan-genome of B. anthracis, we used bioinformatics tools, such as Cluster of
      Orthologous Groups, and performed phylogenetic analysis. We found that the three
      African strains contained the pX01 and pX02 plasmids, the nonsense mutation in
      the plcR gene and the four known prophages. These strains are most similar to the
      CDC684 strain and belong to the A cluster. We estimated that the B. anthracis pan
      genome has 2893 core genes (99% of the genome size) and 85 accessory genes. We
      validated the hypothesis that B. anthracis has a closed pan-genome and found that
      the three African strains carry the two plasmids associated with bacterial
      virulence. The pan-genome nature of B. anthracis confirms its lack of exchange
      (similar to Clostridium tetani) and supports its exclusively pathogenic role,
      despite its survival in the environment. Moreover, thanks to the study of the
      core content single nucleotide polymorphisms, we can see that our three African
      strains diverged very recently from the other B. anthracis strains. 

PMID- 25566395
TI  - First isolation and genomic characterization of enterovirus A71 and
      coxsackievirus A16 from hand foot and mouth disease patients in the Lao PDR.
AB  - Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are major aetiological
      agents of hand, foot and mouth disease in Asia. We established the first genomic
      characterization of strains isolated in 2011 from Lao patients. Isolates were
      related to EV-A71 genotype C4 and CV-A16 genotype B1a that circulated in
      neighbouring countries during the same period. This confirms the regional
      character of hand, foot and mouth disease epidemiology and makes plausible the
      occurrence of severe disease in the Lao population. 

PMID- 25566396
TI  - Identification of OXA-23 carbapenemases: novel variant OXA-239 in Acinetobacter
      baumannii ST758 clinical isolates in Mexico.
AB  - A collection of 15 carbapenem-resistance Acinetobacter baumannii clinical
      isolates was analysed on two tertiary hospitals in Mexico. The OXA-51 was
      identified in all isolates, followed by OXA-239 and OXA-58; OXA-239 is described
      as a new OXA-23-like allele. These carbapenemases were identified on four clonal
      groups, distributed between two neighbouring hospitals. Acinetobacter baumannii
      is poorly studied in Mexico; this situation urges the implementation of
      strategies to prevent its dissemination. 

PMID- 25566397
TI  - Bronchiolitis and bacteraemia caused by Burkholderia gladioli in a non-lung
      transplantation patient.

PMID- 25566399
TI  - New microbes and new infections.

PMID- 25566398
TI  - Diagnosis of human granulocytic anaplasmosis in Belgium by combining molecular
      and serological methods.
AB  - We report here one new, hospitalized case of Anaplasma phagocytophilum in
      Belgium. The clinical presentation of anaplasmosis, its treatment and the
      molecular and serological relevant laboratory methods are briefly developed. 

PMID- 25566400
TI  - A review of assistive listening device and digital wireless technology for
      hearing instruments.
AB  - Assistive listening devices (ALDs) refer to various types of amplification
      equipment designed to improve the communication of individuals with hard of
      hearing to enhance the accessibility to speech signal when individual hearing
      instruments are not sufficient. There are many types of ALDs to overcome a
      triangle of speech to noise ratio (SNR) problems, noise, distance, and
      reverberation. ALDs vary in their internal electronic mechanisms ranging from
      simple hard-wire microphone-amplifier units to more sophisticated broadcasting
      systems. They usually use microphones to capture an audio source and broadcast it
      wirelessly over a frequency modulation (FM), infra-red, induction loop, or other
      transmission techniques. The seven types of ALDs are introduced including
      hardwire devices, FM sound system, infra-red sound system, induction loop system,
      telephone listening devices, television, and alert/alarm system. Further
      development of digital wireless technology in hearing instruments will make
      possible direct communication with ALDs without any accessories in the near
      future. There are two technology solutions for digital wireless hearing
      instruments improving SNR and convenience. One is near-field magnetic induction
      combined with Bluetooth radio frequency (RF) transmission or proprietary RF
      transmission and the other is proprietary RF transmission alone. Recently
      launched digital wireless hearing aid applying this new technology can
      communicate from the hearing instrument to personal computer, phones, Wi-Fi,
      alert systems, and ALDs via iPhone, iPad, and iPod. However, it comes with its
      own iOS application offering a range of features but there is no option for
      Android users as of this moment. 

PMID- 25566401
TI  - Interpretation of Epithelial Lining Fluid Concentrations of Antibiotics against
      Methicillin Resistant Staphylococcus aureus.
AB  - Although antibiotics whose epithelial lining fluid (ELF) concentrations are
      reported high tend to be preferred in treatment of pneumonia, measurement of ELF
      concentrations of antibiotics could be misled by contamination from lysis of ELF
      cells and technical errors of bronchoalveolar lavage (BAL). In this review, ELF
      concentrations of anti-methicillin resistant Staphylococcus aureus (MRSA)
      antibiotics were interpreted considering above confounding factors. An equation
      used to explain antibiotic diffusion into CSF (cerebrospinal fluid) was adopted:
      ELF/free serum concentration ratio = 0.96 + 0.091 * ln (partition coefficient /
      molecular weight(1/2)). Seven anti-MRSA antibiotics with reported ELF
      concentrations were fitted to this equation to see if their ELF concentrations
      were explainable by the penetration capacity only. Then, outliers were modeled
      under the assumption of varying contamination from lysed ELF cells (test range 0
      10% of ELF volume). ELF concentrations of oritavancin, telavancin, tigecycline,
      and vancomycin were well described by the diffusion equation, with or without
      additional impact from cell lysis. For modestly high ELF/free serum concentration
      ratio of linezolid, technical errors of BAL should be excluded. Although
      teicoplanin and iclaprim showed high ELF/free serum ratios also, their protein
      binding levels need to be cleared for proper interpretation. At the moment, it
      appears very premature to use ELF concentrations of anti-MRSA antibiotics as a
      relevant guide for treatment of lung infections by MRSA. 

PMID- 25566403
TI  - Early Additional Immune-Modulators for Mycoplasma pneumoniae Pneumonia in
      Children: An Observation Study.
AB  - BACKGROUND: Mycoplasma pneumoniae (MP) pneumonia is a self-limiting disease, but
      some patients complain of progressive pneumonia, despite of appropriate
      antibiotic treatment. We aimed to introduce the role of immune-modulators
      (corticosteroid and/or intravenous immunoglobulin, IVIG) treatment for childhood
      MP pneumonia based on previous our experiences. MATERIALS AND METHODS: A
      retrospective case series analysis for 183 children with MP pneumonia was
      performed. MP pneumonia patients were diagnosed by two Immunoglobulin M (IgM)
      tests: the micro-particle agglutination method (>=1:40) and the cold
      agglutination test (>=1:4), and were examined twice at the initial admission and
      at discharge. Among 183 MP pneumonia patients, 90 patients with persistent fever
      for over 48 hours after admission or those with severe respiratory symptoms and
      signs received additional prednisolone (82 patients, 1 mg/kg/day) or intravenous
      methylprednisolone (8 patients, 5-10 mg/kg/day) with antibiotics. Four patients
      with aggravated clinical symptoms and chest radiographic findings after
      corticosteroid treatment received IVIG (1 g/kg/day, 1-2 doses). RESULTS: Mean age
      of 183 patients was 5.5 +/- 3.2 years (6 months-15 years), and the male: female
      ratio was 1.1:1 (96:87). Fifty-seven patients (31%) were seroconverters and 126
      seropositive patients showed increased diagnostic IgM antibody titres during
      admission (over 4 folds). The majority of the patients who received
      corticosteroids (86/90 cases) showed rapid defervescence within 48 hours with
      improved clinical symptoms, regardless of the used antibiotics. Also, 4 patients
      who received additional IVIG improved both clinically and radiographically within
      2 days without adverse reaction. CONCLUSIONS: In the era of macrolide-resistant
      MP strains, early additional immune-modulator therapy with antibiotics might
      prevent from the disease progression and reduce the disease morbidity without
      adverse reaction.

PMID- 25566404
TI  - Factors Associated with a Strong Response to the T-SPOT.TB in Patients with
      Extrapulmonary Tuberculosis.
AB  - Limited data are available on which factors are associated with strong
      immunologic responses to T-SPOT.TB. We investigated the factors associated with
      strong positive responses in patients with extrapulmonary tuberculosis (E-TB). Of
      173 patients with E-TB who gave positive results on T-SPOT.TB, 26 (15%) with a
      strong positive response (defined as >=1,000 spot-forming units (SFU)/2.5*10(5)
      PBMC to ESAT-6 or CFP-10) and 71 (41%) with a low positive response (<= 99 SFU (6
      99 SFU)/2.5*10(5) PBMC) were further analyzed. Miliary TB was independently
      associated with a strong positive response to T-SPOT.TB, while advanced age and
      immunosuppression were independently associated with weak positive T-SPOT.TB
      responses. 

PMID- 25566402
TI  - Clinical importance and epidemiology of quinolone resistance.
AB  - The quinolone class of antimicrobial agents is one of most widely used classes of
      antimicrobial agents in outpatient and inpatient treatment. However, quinolone
      resistance in gram-positive and gram-negative bacteria has emerged and increased
      globally. This resistance limits the usefulness of quinolones in clinical
      practice. The review summarizes mechanisms of quinolone resistance and its
      epidemiology and implications in the most common clinical settings, urinary tract
      infections, respiratory tract infections, intraabdominal infections, skin and
      skin structure infections, and sexually transmitted diseases. 

PMID- 25566405
TI  - Susceptibility of Glycopeptide-Resistant Enterococci to Linezolid,
      Quinupristin/dalfopristin, Tigecycline and Daptomycin in a Tertiary Greek
      Hospital.
AB  - We investigated the antibiotic susceptibility of glycopeptide-resistant
      enterococci (GRE). Seventy consecutive GRE were tested. Sixty-two isolates were
      identified as Enterococcus faecium (88.6%), and 8 (11.4%) as Enterococcus
      faecalis. All strains were susceptible to linezolid and daptomycin, while 17.1%
      (12/70) and 11.4% (8/70) were resistant to quinupristin/dalfopristin (QD) and
      tigecycline, respectively. All E. faecalis isolates were resistant to QD, while 4
      of 62 (6.5%) E. faecium isolates were resistant to QD. All E. faecalis isolates
      were susceptible to tigecycline, while 14.5% (9/62) E. faecium isolates were
      resistant. Continued surveillance of GRE antibiotic susceptibilities is important
      for combating these multi-resistant nosocomial pathogens. 

PMID- 25566406
TI  - A Case of Rectal Squamous Cell Carcinoma with Metachronous Diffuse Large B Cell
      Lymphoma in an HIV-Infected Patient.
AB  - Diffuse large B cell lymphoma (DLBCL) is one of the most common acquired immune
      deficiency syndrome (AIDS)-defining malignancies among human immunodeficiency
      virus-infected patients, and rectal cancer has recently emerged as a prevalent
      non-AIDS-defining malignancy. We report a case of rectal squamous cell carcinoma
      that was metachronous with DLBCL in an HIV-infected patient who was receiving
      highly active antiretroviral therapy. The patient was diagnosed with DLBCL and
      showed complete remission after chemotherapy. Follow-up imaging showed increased
      uptake at the rectum, previously treated as lymphoma. Repeated biopsy was
      performed and squamous cell carcinoma of the rectum was reported. After
      concurrent chemoradiation therapy, curative resection was performed. 

PMID- 25566407
TI  - Postoperative Abdominal Infection Caused by Corynebacterium minutissimum.
AB  - Corynebacterium minutissimum is a non-spore forming, gram-positive, aerobic or
      facultative anaerobic bacillus. It is the causative organism of erythrasma, a
      common superficial infection of skin, which typically presents as reddish-brown
      macular patches. To date, it has rarely been found to cause invasive disease,
      although other non-diphtheria corynebacteria are becoming increasingly common as
      opportunistic pathogens. We report on a rare case of abdominal infection due to
      C. minutissimum in an immunocompetent adult who was successfully treated with
      intravenous amoxicillin/sulbactam. 

PMID- 25566408
TI  - A Case of Spontaneous Bacterial Peritonitis with Bacteremia Caused by Shewanella
      algae.
AB  - Human infection caused by Shewanella algae is rare, which usually occurred after
      direct contact with seawater or ingestion of raw seafood in the immunocompromised
      host. There have been anecdotal reports about Shewanella infections in human, but
      their pathogenic role and microbiologic data are limited. Here, we report a fatal
      case of spontaneous bacterial peritonitis with bacteremia due to S. algae in a 57
      year-old male with liver cirrhosis who had no history of exposure to seawater or
      raw seafood. Polymicrobial infection with Streptococcus mitis and Escherichia
      coli was combined and the patient died in spite of early appropriate
      antimicrobial therapy and early goal-directed therapy for sepsis. 

PMID- 25566409
TI  - A Case of Disseminated Infection due to Actinomyces meyeri Involving Lung and
      Brain.
AB  - Actinomyces meyeri is rarely isolated in cases of actinomycosis. The
      identification of A. meyeri had historically been difficult and unreliable. With
      the recent development of 16S ribosomal RNA (16S rRNA) sequencing, Actinomyces
      species such as A. meyeri can be isolated much more reliably. A. meyeri often
      causes disseminated disease, which can be secondary to frequent pulmonary
      infections. A penicillin-based regimen is the mainstay of A. meyeri treatment,
      with a prolonged course usually required. Here, we report a case of pulmonary
      actinomycosis with brain abscess caused by A. meyeri that was initially thought
      to represent lung cancer with brain metastasis. 

PMID- 25566410
TI  - Association Between Microbial Bioburden and Healing Outcomes in Venous Leg
      Ulcers: A Review of the Evidence.
AB  - Significance: Venous leg ulcers (VLUs) are susceptible to microbial invasion, and
      serious complications can result without the timely control of infection.
      Diagnosis of wound infection is primarily based on subjective clinical
      characteristics and patient-reported symptoms, and the treatment with
      antimicrobials has not consistently shown improvement in healing outcomes. This
      is a review of studies using bacterial cultures and/or new molecular-based
      methods associating microbial bioburden with healing outcomes in VLU patients,
      with the goal of guiding future studies to better determine significant patterns
      of microbial involvement in chronic wounds. Recent Advances: Studies reviewed
      here use cultivation-based identification of bacteria and next-generation
      sequencing of the bacterial 16S rRNA gene to gain insight into microbial
      bioburden in VLUs. Further application of sophisticated DNA sequencing and
      bioinformatic analyses has the potential to revolutionize our ability to further
      discern, with high resolution, complex microbial communities in chronic wounds.
      Critical Issues: Few previous studies of microbial bioburden in VLUs have
      incorporated the knowledge of clinical treatments, which includes close
      monitoring of patients' symptoms and responses to therapy. Thus, wound care
      practitioners are currently without evidence-based guidance for the diagnosis and
      treatment of wound infections. Future Directions: Clinically relevant
      breakthroughs are possible by combining advanced microbial detection techniques
      with improved study designs that reflect clinical practices. Well-designed
      longitudinal studies have great potential to lead to better evidence-based
      diagnosis of chronic wounds. A greater understanding of microbial bioburden in
      chronic wounds is likely to lead to better therapies that speed healing and
      prevent wound infection without risking the development of antimicrobial
      resistance.

PMID- 25566411
TI  - Bacterial Strain Diversity Within Wounds.
AB  - Significance: Rare bacterial taxa (taxa of low relative frequency) are numerous
      and ubiquitous in virtually any sample-including wound samples. In addition, even
      the high-frequency genera and species contain multiple strains. These strains,
      individually, are each only a small fraction of the total bacterial population.
      Against the view that wounds contain relatively few kinds of bacteria, this newly
      recognized diversity implies a relatively high rate of migration into the wound
      and the potential for diversification during infection. Understanding the
      biological and medical importance of these numerous taxa is an important new
      element of wound microbiology. Recent Advances: Only recently have these numerous
      strains been discovered; the technology to detect, identify, and characterize
      them is still in its infancy. Multiple strains of both gram-negative and gram
      positive bacteria have been found in a single wound. In the few cases studied,
      the distribution of the bacteria suggests microhabitats and biological
      interactions. Critical Issues: The distribution of the strains, their phenotypic
      diversity, and their interactions are still largely uncharacterized. The
      technologies to investigate this level of genomic detail are still developing and
      have not been largely deployed to investigate wounds. Future Directions: As
      advanced metagenomics, single-cell genomics, and advanced microscopy develop, the
      study of wound microbiology will better address the complex interplay of numerous
      individually rare strains with both the host and each other.

PMID- 25566412
TI  - Dynamic Role of Host Stress Responses in Modulating the Cutaneous Microbiome:
      Implications for Wound Healing and Infection.
AB  - Significance: Humans are under constant bombardment by various stressors,
      including psychological anxiety and physiologic injury. Understanding how these
      stress responses influence the innate immune system and the skin microbiome
      remains elusive due to the complexity of the neuroimmune and stress response
      pathways. Both animal and human studies have provided critical information upon
      which to further elucidate the mechanisms by which mammalian stressors impair
      normal wound healing and/or promote chronic wound progression. Recent Advances:
      Development of high-throughput genomic and bioinformatic approaches has led to
      the discovery of both an epidermal and dermal microbiome with distinct
      characteristics. This technology is now being used to identify statistical
      correlations between specific microbiota profiles and clinical outcomes related
      to cutaneous wound healing and the response to pathogenic infection. Studies have
      also identified more prominent roles for typical skin commensal organisms in
      maintaining homeostasis and modulating inflammatory responses. Critical Issues:
      It is well-established that stress-induced factors, including catecholamines,
      acetylcholine, and glucocorticoids, increase the risk of impaired wound healing
      and susceptibility to infection. Despite the characterization of the cutaneous
      microbiome, little is known regarding the impact of these stress-induced
      molecules on the development and evolution of the cutaneous microbiome during
      wound healing. Future Directions: Further characterization of the mechanisms by
      which stress-induced molecules influence microbial proliferation and metabolism
      in wounds is necessary to identify altered microbial phenotypes that
      differentially influence host innate immune responses required for optimal
      healing. These mechanisms may yield beneficial as targets for manipulation of the
      microbiome to further benefit the host after cutaneous injury.

PMID- 25566413
TI  - New Molecular Techniques to Study the Skin Microbiota of Diabetic Foot Ulcers.
AB  - Significance: Diabetic foot ulcers (DFU) are a major and growing public health
      problem. They pose difficulties in clinical practice in both diagnosis and
      management. Bacterial interactions on the skin surface are important in the
      pathophysiology of DFU and may contribute to a delay in healing. Fully
      identifying bacteria present in these wounds is difficult with traditional
      culture methods. New molecular tools, however, have greatly contributed to our
      understanding of the role of the cutaneous microbiota in DFU. Recent Advances:
      Molecular technologies revealed new information concerning how bacteria are
      organized in DFU. This has led to the concept of "functionally equivalent
      pathogroups," meaning that certain bacterial species which are usually
      nonpathogenic (or at least incapable of maintaining a chronic infection on their
      own) may coaggregate symbiotically in a pathogenic biofilm and act
      synergistically to cause a chronic infection. The distribution of pathogens in
      multispecies biofilms is nonrandom. The high bacterial diversity is probably
      related to the development of a microbial biofilm that is irreversibly attached
      to the wound matrix. Critical Issues: Using molecular techniques requires a
      financial outlay for high-cost equipment. They are still too time-consuming to
      perform and reporting is too delayed for them to be used in routine practice.
      Finally, they do not differentiate live from dead or pathogenic from
      nonpathogenic microorganisms. Future Directions: Molecular tools have better
      documented the composition and organization of the skin flora. Further advances
      are required to elucidate which among the many bacteria in the DFU flora are
      likely to be pathogens, rather than colonizers.

PMID- 25566414
TI  - Next-Generation Sequencing: A Review of Technologies and Tools for Wound
      Microbiome Research.
AB  - Significance: The colonization of wounds by specific microbes or communities of
      microbes may delay healing and/or lead to infection-related complication. Studies
      of wound-associated microbial communities (microbiomes) to date have primarily
      relied upon culture-based methods, which are known to have extreme biases and are
      not reliable for the characterization of microbiomes. Biofilms are very resistant
      to culture and are therefore especially difficult to study with techniques that
      remain standard in clinical settings. Recent Advances: Culture-independent
      approaches employing next-generation DNA sequencing have provided researchers and
      clinicians a window into wound-associated microbiomes that could not be achieved
      before and has begun to transform our view of wound-associated biodiversity.
      Within the past decade, many platforms have arisen for performing this type of
      sequencing, with various types of applications for microbiome research being
      possible on each. Critical Issues: Wound care incorporating knowledge of
      microbiomes gained from next-generation sequencing could guide clinical
      management and treatments. The purpose of this review is to outline the current
      platforms, their applications, and the steps necessary to undertake microbiome
      studies using next-generation sequencing. Future Directions: As DNA sequencing
      technology progresses, platforms will continue to produce longer reads and more
      reads per run at lower costs. A major future challenge is to implement these
      technologies in clinical settings for more precise and rapid identification of
      wound bioburden.

PMID- 25566416
TI  - Capgras-like visual decomposition in Lewy body dementia with therapeutic response
      to donepezil.

PMID- 25566415
TI  - Current Concepts and Ongoing Research in the Prevention and Treatment of Open
      Fracture Infections.
AB  - Significance: Open fractures are fractures in which the bone has violated the
      skin and soft tissue. Because of their severity, open fractures are associated
      with complications that can result in increased lengths of hospital stays,
      multiple operative interventions, and even amputation. One of the factors thought
      to influence the extent of these complications is exposure and contamination of
      the open fracture with environmental microorganisms, potentially those that are
      pathogenic in nature. Recent Advances: Current open fracture care aims to prevent
      infection by wound classification, prophylactic antibiotic administration,
      debridement and irrigation, and stable fracture fixation. Critical Issues:
      Despite these established treatment paradigms, infections and infection-related
      complications remain a significant clinical burden. To address this, improvements
      need to be made in our ability to detect bacterial infections, effectively remove
      wound contamination, eradicate infections, and treat and prevent biofilm
      formation associated with fracture fixation hardware. Future Directions: Current
      research is addressing these critical issues. While culture methods are of
      limited value, culture-independent molecular techniques are being developed to
      provide informative detection of bacterial contamination and infection. Other
      advanced contamination- and infection-detecting techniques are also being
      investigated. New hardware-coating methods are being developed to minimize the
      risk of biofilm formation in wounds, and immune stimulation techniques are being
      developed to prevent open fracture infections.

PMID- 25566417
TI  - NMDA receptor encephalitis causing reversible caudate changes on MRI and PET
      imaging.

PMID- 25566418
TI  - Acute changes in ventricular volume during treatment for hepatic and renal
      failure.

PMID- 25566419
TI  - Autoimmune encephalitis mimicking Creutzfeldt-Jakob disease.

PMID- 25566420
TI  - Sensory neuronopathy associated with tumor necrosis factor inhibitor therapy.

PMID- 25566421
TI  - Alternating ictal and postictal nystagmus.

PMID- 25566422
TI  - Effects of blood flow to the prefrontal cortex on high-intensity exercise
      combined with high-decibel music.
AB  - We studied the effects of high-intensity exercise (70-75% of VO2 max) combined
      with high-decibel music (100 dB) on cognitive function (measured by the Stroop
      test) and related blood flow changes to the prefrontal cortex (measured by Oxy
      hemoglobin (Hb), Deoxy-Hb, tissue oxygen index (TOI), and normalized tissue
      hemoglobin index (nTHI)). The subjects of the study were 28 healthy female
      university students in their early 20s. Subjects were categorized into control
      group (CG), music group (MG), exercise group (Ex), and music and exercise group
      (MnEx). A crossover design was implemented so that all subjects participated in
      all test groups. We found no significant difference in reaction time between CG
      and MG for the neutral and incongruent tasks of Stroop test. However, there were
      significant improvements in the neutral and incongruent tasks for both the Ex (p
      < 0.01) and MnEx (p < 0.01) groups. Oxy-Hb measurements in the prefrontal cortex
      of the brain supported the Stroop test data. We found no difference between Ex
      and MnEx in the TOI; however, there was a significant decrease (p < 0.05) in MnEx
      compared to Ex. In addition, Ex resulted in a significant increase (p < 0.05) in
      nTHI as compared to CG. These results indicate that high decibel music could
      negatively affect prefrontal cortex activation of the brain during exercise. 

PMID- 25566423
TI  - The effect of restriction of dietary calcium on trabecular and cortical bone
      mineral density in the rats.
AB  - This study aimed to investigate effects of restricted calcium intake on cortical
      and trabecular bone density in white rats. Low Ca diet was fed for six weeks, and
      bone density and bone metabolism parameters were assessed in blood. This study
      was carried out on 12 male white rats aged 12 weeks (Sprague-Dawley; SD). These
      rats were bred for 1 week and randomly assigned to the standard calcium diet
      group (SCa group, n = 6) and the low calcium diet group (LCa group; n = 6). The
      SCa group was given a modified AIN-93M mineral mix (with 0.5% Ca), which was made
      by adding calcium to a standard AIN93 diet, and the LCa Group was fed a modified
      AIN-93 Mineral mix (with 0.1% Ca). Femoral BMD and BMC were measured by DEXA in
      each rat. After trabecular bone was separated from cortical bone, volumetric bone
      mineral density (vBMD) was measured using pQCT. Serum Ca and P levels were
      measured as parameters of bone metabolism, and S-ALP, S-TrACP and-Dpd levels were
      also measured. The results revealed no significant differences in weight, growth
      rate, feed consumption and feed efficiency between the two groups before and
      after calcium-restricted diet (p > .05). No significant differences were also
      observed in bone length and bone mass between the two groups (p > .05). Although
      bilateral femoral BMDs were not significantly different between the two groups,
      bilateral femoral BMCs significantly decreased in the LCa group, compared with
      the SCa group (p = .023, p = .047). Bilateral cortical MDs were not significantly
      different between the two groups, either. However, trabecular BMD significantly
      decreased in the LCa group, compared with the SCa group (p = .041). U-Dpd and S
      TrACP levels significantly declined in the LCa group, compared to the SCa group
      (p = .039, p = .010). There were no significant differences in serum Ca and P
      levels between the two groups (p > .05). However, a significant decrease in
      urinary Ca level (p = .001) and a significant increase in urinary P (p = .001)
      were observed in the LCa group, compared to the Sca group. These findings
      described that six-week low calcium diet led to decreased trabecular bone
      density, reduced urinary excretion of Ca and increased urinary excretion of P. As
      a result, Ca hemeostasis can be maintained. 

PMID- 25566424
TI  - Effects of muscular and aqua aerobic combined exercise on metabolic indices in
      elderly women with metabolic syndrome.
AB  - The purpose of this study was to investigate the effects of muscle strengthening
      exercise using elastic thera-band and aquatic aerobic combined exercise on
      metabolic syndrome index in elderly with metabolic syndrome. Fifty-four were
      assigned to muscle strengthening exercise group (n = 19), aquatic aerobic
      exercise group (n = 19), and combined exercise group (n = 16). The muscle
      strength exercise, aquatic aerobic exercise and combined exercise were provided
      three times a week for 12 weeks. Metabolic syndrome indices[Fasting blood
      glucose, triglyceride, high density lipoprotein cholesterol (HDL-C), systolic
      blood pressure, diastolic blood pressure and waist circumference] were measured
      before and after the program. One-way ANOVA, paired t-test and two-way repeated
      ANOVA were used with the SPSS program for data analysis. There was a significant
      difference in triglyceride (p < .001), HDL-C (p = .010) and waist circumference
      (p = .016). Triglyceride and waist circumference was significantly decreased in
      combined group than muscle strength exercise group and aquatic exercise group.
      HDL-C was significantly increased in combined group than muscle strength exercise
      group. The results indicate that combined exercise was more effective in the
      improvement of dyslipidemia and abdominal obesity. 

PMID- 25566425
TI  - Serum Vitamin D status and its relations to body fatness and fitness and risk
      factors in young adults.
AB  - The study examined the relations of serum vitamin D levels to body fatness,
      cardiorespiratory fitness (CRF), and metabolic risk factors in young adults in
      Korea. A total of 593 young men completed a health examination, body fatness,
      maximal treadmill exercise test, and assessment of metabolic risk factors.
      Participants were classified by serum vitamin D levels as deficient (< 20 ng/mL),
      insufficient (20~30 ng/mL), and sufficient (> 30 ng/mL). Body fatness, CRF, and
      metabolic risk factors were evaluated according to serum vitamin D
      classification. Significant inverse trends in body fatness and metabolic risk
      factors were observed, as was a significant linear trend for CRF across
      incremental vitamin D categories in this study population. Serum vitamin D levels
      were negatively associated with body fatness parameters, blood pressures, total
      cholesterol, triglycerides, and insulin and positively associated with high
      density lipoprotein cholesterol and CRF. Compared to the BMI-based lean group,
      the obese groups had significantly higher odds ratio for serum vitamin D
      insufficiency before and after adjusting for age, CRF, and physical activity.
      Similarly, compared to percent body fat- and waist circumference-based lean
      groups, the obese groups had significant higher odds ratios for serum vitamin D
      insufficiency. In conclusion, the current findings of the study suggest that
      along with vitamin D intakes, body fat loss and outdoor physical activity should
      be promoted as non-pharmacologic means to improve metabolic risk factors in young
      adults. 

PMID- 25566427
TI  - The estimation of mineral contents in oriental supplements consumed by elite
      athletes.
AB  - The purpose of this study is twofold: to examine macro (calcium, magnesium, and
      phosphorus) and trace mineral (iron) concentration in oriental supplements (OS),
      and to define OS prevalence in elite athletes. Participants of this study were
      928 varsity athletes (male: 680, female: 248) with 23 sports types. Recent 3
      month dietary supplements (DS) and OS practice was surveyed during training
      period, and mineral concentration in 72 randomly collected OS samples were
      analyzed. DS use was 41% and OS use was 20% in university elite athletes. Most
      common OS use informants were parents (74%). OS intake reason was for health
      maintenance (37%), energy supplement (25%), and recovery improvement (15%).
      Moreover, health maintenance was higher in females (47%) than males (32%) while
      energy supplement was higher in males (28%) than females (18%) (chi(2)(8) =
      17.676, p = 0.024). Beliefs in OS efficacy and importance were significantly
      higher in female athletes compared to male athletes (p < 0.05). Macro mineral
      concentration in OS was calcium (7.54 ppm), magnesium (4.63 ppm), and phosphorus
      (205.34 ppb) and trace mineral concentration in OS was iron (8.10 ppb), which was
      a small amount. An association between OS intake reason and mineral concentration
      in calcium, phosphorus, and iron was found, but no association between OS intake
      and magnesium. In conclusion, an association between OS intake reason and mineral
      concentration differed by the ingredients. Minerals in OS were very small amount,
      which would be improved for mineral balance in elite athletes. 

PMID- 25566426
TI  - Neuroprotective effects of treadmill exercise on BDNF and PI3-K/Akt signaling
      pathway in the cortex of transgenic mice model of Alzheimer's disease.
AB  - (AD). Although physical exercise and AD have received attention in the scientific
      literature, the mechanism through which treadmill exercise may impact the brain
      insulin signaling of AD has not been elucidated. This study aimed to evaluate the
      neuroprotective effects of treadmill exercise on apoptotic factors (Bcl-2/Bax
      ratio, caspase-3), HSP70, COX-2, BDNF and PI3-K/Akt signaling pathway in the
      cortex of NSE/hPS2m transgenic mice model of AD. Treadmill exercise ameliorated
      cognitive function in water maze test and significantly increased the level of
      Bcl-2/Bax ratio and HSP-70 in Tg-exe group compared to Tg-con group; on the other
      hand, it significantly decreased the expression of caspase-3 and COX-2 in Tg-exe
      group compared to Tg-con group. In addition, treadmill exercise significantly
      increased the expression of BDNF and PI3K/Akt in Tg-exe group compared to Tg-con
      group. Consequently, treadmill exercise improves cognitive function possibly via
      activating neurotrophic factor, BDNF and PI3k/Akt signaling pathway, and Abeta
      induced neuronal cell death in the cortex of Tg mice was markedly suppressed
      following treadmill exercise. These results suggest that treadmill exercise may
      be beneficial in preventing or treating Alzheimer's disease. 

PMID- 25566428
TI  - Effect of BCAA intake during endurance exercises on fatigue substances, muscle
      damage substances, and energy metabolism substances.
AB  - The increase rate of utilization of branched-chain amino acids (BCAA) by muscle
      is reduced to its plasma concentration during prolonged exercise leading to
      glycogen. BCAA supplementation would reduce the serum activities of intramuscular
      enzymes associated with muscle damage. To examine the effects of BCAA
      administration on fatigue substances (serotonin, ammonia and lactate), muscle
      damage substances (CK and LDH) and energy metabolism substances (FFA and glucose)
      after endurance exercise. Subjects (n = 26, college-aged males) were randomly
      divided into an experimental (n = 13, EXP) and a placebo (n = 13, CON) group.
      Subjects both EXP and CON performed a bout of cycle training (70% VO2max
      intensity) to exhaustion. Subject in the EXP were administrated BCAA (78ml/kg.w)
      prior to the bout of cycle exercise. Fatigue substances, muscle damage substances
      and energy metabolism substances were measured before ingesting BCAAs and
      placebos, 10 min before exercise, 30 min into exercise, immediately after
      exercise, and 30 min after exercise. Data were analyzed by two-way repeated
      measure ANCOVA, correlation and statistical significance was set at p < 0.05. The
      following results were obtained from this study; 1. In the change of fatigue
      substances : Serotonin in the EXP tended to decreased at the 10 min before
      exercise, 30 min into exercise, post exercise, and recovery 30 min. Serotonin in
      the CON was significantly greater than the EXP at the10 min before exercise and
      recovery 30. Ammonia in the EXP was increased at the 10 min before exercise, 30
      min into exercise, and post exercise, but significantly decreased at the recovery
      30min (p < 0.05). Ammonia in the CON was significantly lower than the EXP at the
      10 min before exercise, 30 min into exercise, and post exercise (p < 0.05).
      Lactate in the EXP was significantly increased at the 30 min into exercise and
      significantly decreased at the post exercise and recovery 30 min. Lactate in the
      CON was significantly lower than the EXP at the post exercise (p < 0.05). 2. In
      the change of muscle damage substances : CK in the EXP was decreased at the 10
      min before exercise and increased at the 30 min into exercise and then decreased
      at the post exercise and recovery 30 min. CK in the CON was greater than the EXP.
      LDH in the EXP was decreased at the 10 min before exercise and increased at the
      30 min into exercise and then decreased at the post exercise and recovery 30 min.
      LDH in the CON was higher than the EXP. 3. In the change of energy metabolism
      substances :Glucose in the EXP tended to decrease at the 10 min before exercise,
      30 min into exercise, post exercise and recovery 30 min. Glucose in the CON was
      significantly greater than the EXP at the recovery 30 min (p < .05). FFA in both
      EXP and CON was increased at the post exercise and recovery 30 min. % increase
      for FFA in the EXP was greater than the CON at the post exercise and recovery 30
      min. 4. The relationship of the fatigue substances, muscle damage substances and
      energy metabolism substances after endurance exercise indicated strongly a
      positive relationship between LDH and ammonia and a negative relationship between
      LDH and FFA in the EXP. Also, there were a strong negative relationship between
      glucose and FFA and a positive relationship between glucose and serotonin in the
      EXP. There was a strong positive relationship between CK and LDH and a strong
      negative relationship between FFA and glucose in the CON. These results indicate
      that supplementary BCAA decreased serum concentrations of the intramuscular
      enzymes as CK and LDH following exhaustive exercise. This observation suggests
      that BCAA supplementation may reduce the muscle damage associated with endurance
      exercise. 

PMID- 25566429
TI  - Effects of exercise and diet composition on expression of MCP-1 and oxidative
      stress-related mRNA of adipose tissue in diet-induced obese mice.
AB  - The aim of the study was to analyze how the expression of MCP-1, HIF-1alpha,
      NOX2, ERK1, ERK2, and Mn-SOD mRNA, which are related to inflammation and
      oxidative stress and which can influence the accumulation of macrophage in obese
      adipose tissue, differed according to a high-fat diet, change of diet
      composition, and exercise. Obesity was induced using a high-fat diet (45% fat)
      for five weeks. This investigation analyzed how the change of diet composition
      for eight weeks and long-term exercise training affected the expression of mRNA
      in epididymal white adipose tissue. For the experiment, 56 four-week-old C57BL/6
      mice were used. Their epididymal white adipose tissue was extracted and used in
      RT-PCR analysis to find the expression level of mRNA. A high-fat diet for 13
      weeks showed a significant increase in the expression of MCP-1, HIF-1alpha, NOX2,
      and ERK1 mRNA in epididymal adipose tissue. Change in diet composition and
      exercise decreased the expression of MCP-1, HIF-1alpha, NOX2, and ERK1 mRNA.
      Particularly, the group combining a high-fat diet and exercise had a significant
      increase in the expression of Mn-SOD mRNA in epididymal adipose tissue; however,
      it showed a significant decrease in MCP-1, HIF-1alpha, and NOX2. These results
      suggest that the antioxidant effect and weight loss by exercise decreased
      inflammation and oxidative stress. 

PMID- 25566430
TI  - The effects of endurance training and thiamine supplementation on anti-fatigue
      during exercise.
AB  - The purpose of this study was to find the effect of endurance training and
      thiamine supplementation on anti-fatigue during the exercise. Each nine students
      from K Women's University went through three cross-over treatments: placebo
      treatment, training treatment and thiamine treatment. Training treatment was
      performed with bicycle ergometer exercise for four weeks (five days per week).
      Each exercise was performed for an hour with intensity set at 70% (50rpm) of
      maximal oxygen uptake. Thiamine treatment group was given 10mg of thiamine
      tetrahydrofurfuryl disulfide per one kilogram for four weeks. The bicycle
      ergometer exercise was performed at 70% of maximal oxygen uptake in exercise
      intensity which 60 minutes of exercise was performed at 50rpm . Lactate
      concentration was significantly decreased during 15 to 30 minutes of exercise for
      those with training treatment and 15 to 60 minutes of exercise for those with
      thiamine treatment compared to placebo treatment group. Ammonia concentration was
      significantly decreased during 15 to 60 minutes of exercise and 15 to 30 minutes
      of recovery for those with training and thiamine treatment compared to placebo
      treatment. Resting blood thiamine concentrations of placebo treatment were
      significantly lower than training treatment. 60 minutes after the exercise,
      plasma thiamine concentration was significantly increased in all treatment group.
      To sum up the previous, thiamine intake during exercise positively benefits
      carbohydrate metabolism in a way that will decrease lactate concentration,
      ammonia concentration, and anti- fatigue by reducing the RPE. Therefore, we can
      consider thiamine intake to be utilized as similar benefits as endurance
      training. 

PMID- 25566431
TI  - The effects of treadmill exercise on expression of UCP-2 of brown adipose tissue
      and TNF-alpha of soleus muscle in obese Zucker rats.
AB  - Sorts of abnormal state, obesity and inflammation are involved in a number of
      serious disease occurring and both of them became important research topics among
      molecular biologists. UCP-2 and TNF-alpha respectively reflecting obese and
      inflammatory status have often been used to evaluate the effects of independent
      variable, such as exercise, on them. Because exercise has shown its potent
      control on obesity and inflammation, it is necessary to determine if exercise is
      working via same bioindices. The purpose of this study was to determine the
      effects of different treadmill exercise intensities on UCP-2 of brown adipose
      tissue and TNF-alpha of soleus muscle during 8 weeks in Zucker rat. Zucker rats
      were divided into four groups (n = 7 in each group): control group, low intensity
      exercise group, moderate intensity exercise group and high intensity exercise
      group. Zucker rats of the exercise groups were made to run on a motorized
      treadmill for 30 minutes once a day during 8 weeks. Rats were sacrificed 24 hours
      after the last bout of exercise. Blood glucose in Zucker rats were measured by
      Gluco-Card II. Brown adipose tissue were extracted to analyze the level of UCP-2
      and TNF-alpha, respectively. UCP-2 and TNF-alpha were analyzed using the Western
      Blotting technique. Statistical techniques for data analysis were repeated
      measure ANOVA and one way ANOVA to determine the difference between groups, and
      for post hoc test was Duncan' test. The 5% level of significance was utilized as
      the critical level for acceptance of hypotheses for the study. The following
      results were obtained from this study; UCP-2 protein expression of brown adipose
      tissue in Zucker rats were increased significantly following exercise of the low
      and moderate intensities compared to those of control group after 8 weeks. It was
      shown that TNF-alpha protein expression of soleus muscle in Zucker rats were
      decreased significantly following exercise of the low and moderate intensities
      compared to those of control group after 8 weeks. But no significant differences
      in levels of fasting glucose were shown between groups. The present data
      suggested that low and moderate intensities treadmill exercise may improve
      glycometabolism control and fat oxidation by up-regulating UCP-2 expression. In
      addition, we found low and moderate intensities reduce damages on skeletal muscle
      by down-regulation the TNF-alpha in Zucker rats. Thus, the low and moderate
      intensity exercise are appropriate for anti-obesity and inflammatory effects. 

PMID- 25566432
TI  - Effects Ala54Thr polymorphism of FABP2 on obesity index and biochemical variable
      in response to a aerobic exercise training.
AB  - The purpose of the current study was to investigate whether or not the FABP2 gene
      polymorphism modulated obesity indices, hemodynamic factor, blood lipid factor,
      and insulin resistance markers through 12-week aerobic exercise training in
      abdominal obesity group of Korean mid-life women. A total of 243 abdominally
      obese subjects of Korean mid-life women voluntarily participated in aerobic
      exercise training program for 12 weeks. Polymerase Chain Reaction with
      Restriction Fragment Length Polymorphism (PCR-RFLP) assay was used to assess the
      FABP2 genotype of the participants (117 of AA homozygotes, 100 of AT
      heterozygotes, 26 of TT homozygotes). Prior to the participation of the exercise
      training program, baseline obesity indices, hemodynamic factor, blood lipid
      factor, and insulin resistance markers were measured. All the measurements were
      replicated following the 12-week aerobic exercise training program, and then the
      following results were found. After 12-week aerobic exercise training program,
      wild type (Ala54Ala) and mutant type (Ala54Thr+Thr54Thr) significantly decreased
      weight (P > .001), BMI (P > .001), %bf (P > .001), waist circumference (P >
      .001), WHR (P > .001), muscle mass (wild type p < .022; mutant type P > .001),
      RHR (P > .001), viseceral adipose area (wild type p < .005; mutant type P >
      .001), subcutaneous area (P > .001), insulin (wild type p < .005; mutant type P >
      .001) and significantly increased VO2max (P > .001). And wild type significantly
      decresed NEFA (P > .05), glucose (P > .05), OGTT 120min glucose (P > .05) and
      significantly increased HDLC (p > .005). Mutant type significantly decreased SBP
      (P > .001), DBP (P > .01), TC (P > .01), LPL (P > .05), LDL (P > .001), HOMA
      index (P > .01). The result of the present study represents that regular aerobic
      exercise training may beneficially prevent obesity index, blood pressure, blood
      lipids and insulin resistance markers independent of FABP Ala54Thr wild type and
      mutant type. 

PMID- 25566433
TI  - The effect of SIRT1 protein knock down on PGC-1alpha acetylation during skeletal
      muscle contraction.
AB  - PURPOSE: The purpose of this study was to investigate the effect of Sirtuin 1
      (SIRT1) and General control nonderepressible 5 (GCN5) knock down on peroxisome
      proliferator- activated receptor gamma coactivator 1-alpha (PGC-1alpha)
      deacetylation during electrical stimulated skeletal muscle contraction. METHODS:
      Skeletal muscle primary cell were isolated from C57BL/6 mice gastrocnemius and
      transfected lentiviral SIRT1 and GCN5 shRNA. Knock downed muscle cell were
      stimulated by electrical stimulation (1Hz, 3min) and collected for PGC-1alpha
      deceatylation assays. Immunoprecipitation performed for PGC-1alpha deacetylation,
      acetyl-lysine level was measured. RESULTS: Our resulted showed SIRT1 knock down
      not influenced to PGC-1alpha deacetylation during electrical stimulation induced
      muscle contraction while GCN5 knock down decreased PGC-1alpha deacetylation
      significantly (p<0.05). CONCLUSION: This study can be concluded that GCN5 is a
      critical factor for muscle contraction induced PGC-1alpha deacetylation.

PMID- 25566434
TI  - The effect of exercise training and water extract from propolis intake on the
      antioxidant enzymes activity of skeletal muscle and liver in rat.
AB  - PURPOSE: In this study, the authors have intended to investigate the effects that
      the exercise training and the intake of the water extract from propolis have on
      the activity of antioxidant enzymes. METHODS: For this purpose, the exercise
      training (70% VO2max treadmill running exercise for 60min)of 5 times per week for
      six weeks and the intake (50mg/kg/day) of the water extract from propolis were
      performed by separating the experimental animals (SD rats, n=32) into CON(n=8)
      group, CON+Ex(n=8), PA(n=8), and PA+Ex(n=8). RESULTS: As a result, the following
      conclusions were obtained: The concentration of the blood glucose and insulin of
      the CON+Ex group and PA+Ex group which are the exercise parallel group were
      significantly decreased in comparison with the control group, whereas if
      comparing the glycogen concentration in skeletal muscle and liver tissue between
      the exercise parallel group and the CON group, the former showed significantly
      high value in comparison with the latter (p < .05). In the case of the activity
      of the antioxidant enzyme in the skeletal muscle and the liver tissue, the
      activities of SOD, GPX and CAT in the gastrocnemius muscle tissue of the
      experimental animals showed significantly high value in PA+Ex group in comparison
      with other experimental groups (p < .05). In addition, the SOD activity in the
      liver tissue showed that only PA+Ex group was significantly increased, whereas
      GDX activity showed significantly higher value in CON+Ex group and PA group than
      CON group (p < .05). However, the activity of CAT in the liver tissue showed that
      there is no difference between the experimental groups. As a result that measured
      the concentration of MDA in order to evaluate the damage level of the tissue by
      oxygen free radicals, the difference between the groups in the liver tissue was
      not shown, while it was shown that only PA+Ex group in the skeletal muscle tissue
      was significantly decreased in comparison with other experimental groups (p <
      .05). CONCLUSION: Taken together the above findings, it is considered that the
      parallel treatment of the exercise training and the water extract from propolis
      can not only increase the use of glycogen of the skeletal muscle and liver
      tissue, but also it can give the effect to suppress the creation of active oxygen
      by inducing the activity of the antioxidant enzyme in the body, and in the
      future, the possibility as the exercise supplements and the antioxidant of the
      water-soluble propolis are expected.

PMID- 25566435
TI  - Effects of aquatic exercise and CES treatment on the changes of cognitive
      function, BDNF, IGF-1, and VEGF of persons with intellectual disabilities.
AB  - PURPOSE: The purpose of this study was to investigate the effects of aquatic
      exercise and CES treatment on the cognitive function by using K-WAB and BDNF, IGF
      1, and VEGF of persons with intellectual disabilities. METHODS: All subjects were
      15 male with intellectual disabilities who were participating in the aquatic
      training program and CES treatment during 12 weeks at rehabilitation center. The
      subjects were divided into control group, exercise group, and exercise+CES group.
      Blood samples for BDNF, IGF-1, and VEGF were taken from brachial vein at rest
      between before and after treatment. RESULTS: The results are summarized as
      follows: Cognitive function level increased significantly in the exercise+CES
      group compared to those in the exercise and control group. The changes of blood
      IGF-1 concentration were no significant difference among groups. The changes of
      blood BDNF and VEGF concentration were significantly increased in exercise group
      and exercise+CES group than control group. However, blood BDNF and VEGF
      concentration were significantly difference between exercise group and
      exercise+CES group. CONCLUSION: In conclusion, it can be concluded that CES
      treatment with exercise can amend cognitive function of persons with intellectual
      disabilities more effectively and increase of BDNF and VEGF by exercise can
      explain the cognitive function improvement of persons with intellectual
      disabilities.

PMID- 25566436
TI  - Accuracy of predicted resting metabolic rate and relationship between resting
      metabolic rate and cardiorespiratory fitness in obese men.
AB  - PURPOSE: The purpose of this study is to examine that not only the relationship
      of the resting metabolic rate (RMR) and cardiorespiratory fitness(VO2peak), but
      also the comparison between measured and predicted results of RMR in obese men.
      METHODS: 60 obese men (body fat>32%) were recruited for this study. They did not
      participate in regular exercising programs at least 6 months. The RMR was
      measured with indirect calorimetry and predicted RMR using Herris-Benedicte
      equation. The cardiorespiratory fitness was determined by directly measuring the
      oxygen consumption (VO2peak) during the exercise on the treadmill. RESULTS: The
      significance for the difference between the measured results and predicted result
      of RMR were tested by paired t-test. Correlation of measured date was obtained by
      Pearson correlation coefficient. The value of predicted RMR and measured RMR were
      significantly different in these obese subjects. (p < 0.001). The difference
      between RMR cardiorespiratory fitness and cardiorespiratory fitness showed
      significant correlation (r=0.67, p < 0.05). CONCLUSION: The current formulas of
      predicted RMR have limited the evaluation of measured RMR for Korean obese men.
      Therefore, this study suggests that new formula should be designed for Korean in
      order to obtain more accurate results in obese.

PMID- 25566437
TI  - Effect of energy drink dose on exercise capacity, heart rate recovery and heart
      rate variability after high-intensity exercise.
AB  - PURPOSE: The purpose of this research was to investigate the effects of exercise
      capacity, heart rate recovery and heart rate variability after high-intensity
      exercise on caffeine concentration of energy drink. METHODS: The volunteers for
      this study were 15 male university student. 15 subjects were taken basic physical
      examinations such as height, weight and BMI before the experiment. Primary tests
      were examined of VO2max per weight of each subjects by graded exercise test using
      Bruce protocol. Each of five subject was divided 3 groups (CON, ECGI, ECGII) by
      matched method based on weight and VO2max per weight what gained of primary test
      for minimize the differences of exercise capacity and ingestion of each groups.
      For the secondary tests, the groups of subjects were taken their materials before
      and after exercise as a blind test. After the ingestion, subjects were
      experimented on exercise test of VO2max 80% by treadmill until the all-out. Heart
      rate was measured by 1minute interval, and respiratory variables were analyzed
      VO2, VE, VT, RR and so on by automatic respiratory analyzer. And exercise
      exhaustion time was determined by stopwatch. Moreover, HRV was measured after
      exercise and recovery 3 min. RESULTS: Among the intake groups, ECGII was showed
      the longest of exercise exhaustion time more than CON group (p = .05). Result of
      heart rate during exercise according to intake groups, there was significant
      differences of each time (p < .001), however, not significant differences of each
      groups and group verse time (p > .05). Result of RPE during exercise according to
      intake groups, there was significant differences of each time (p < .001),
      however, not significant differences of each groups and group verse time (p >
      .05). CONCLUSION: In conclusion, EDGII showed the significant increase of
      exercise exhaustion time more than CON group (p=.05) and not significant
      differences in HR, RPE, RER, HRV, HRR, blood pressure (p > .05). Therefore, 2.5
      mg/kg(-1) ingestion of energy drink might be positive effect to increase exercise
      performance capacity without side-effect in cardiovascular disease.

PMID- 25566438
TI  - Effect of intake of gardenia fruits and combined exercise of middle-aged obese
      women on hormones regulating energy metabolism.
AB  - PURPOSE: This study is aimed at analyzing how exercise and gardenia affect
      hormones that regulate energy metabolism by having middle aged, obese women
      exercise and take gardenia simultaneously. METHODS: This study assigned a total
      of 35 middle-aged obese women with body fat percentage of more than 35 percent
      into 9 people of the complex treatment group of intake of gardenia and exercise,
      9 people of the exercise group, 9 people of the gardenia group and 8 people of
      the control group in order to find out the effect of the intake of gardenia
      fruits and Combined exercise of 8 weeks on the body composition, hormones
      regulating energy metabolism. This study arranged .08 g per weight of 1 kg of the
      gardenia fruits to be taken twice a day for 8 weeks after breakfast and dinner
      through the numerical method of roasting the gardenia fruits on fire. And the
      exercise program was set to be five times a week for 8 weeks, whereas the aerobic
      exercise of 60 to 70 minutes was 50 to 60 percent for HRmax; thus, the resistance
      exercise was set to be 1-RM 50 percent. As for the data analysis, the two-way
      repeated measures ANOVA was utilized for the analysis of interactive effect
      between groups and times. RESULTS: Thus, the obtained conclusion is as follows:
      The %fat and WHR has decreased further in the gardenia+exercise group and the
      exercise group as compared with the control group. And the visceral fat area has
      decreased further in the gardenia and exercise group and the gardenia group as
      compared with the control group (p<.05). In addition, the gardenia+exercise group
      and the exercise group were found to have a significant improvement effect in all
      the items of body composition, and the gardenia group has reduced the fat
      percentage and BMI after the treatment (p<.05). Leptin has decreased further in
      the gardenia+exercise group and the exercise group as compared with the control
      group, and the insulin resistance and GLP-1 have decreased in all the treatment
      groups (p<.05). CONCLUSION: As a result of this study, all the treatment groups
      were found to have an improvement effect of research variables in general;
      therefore, the single treatment and complex treatment for the middle-aged obese
      women were found to have a positive impact on body composition, adjusting factors
      for energy metabolism. Also, the complex treatment was found to be more positive
      in terms of change amount. In particular, in the case of visceral fat area that
      is the major risk factor for metabolic disease of middle-aged obese women, it was
      found to have decreased further in the complex treatment group than the gardenia
      group; therefore, the complex treatment was found to be more advantageous.

PMID- 25566439
TI  - Exercise, but not quercetin, ameliorates inflammation, mitochondrial biogenesis,
      and lipid metabolism in skeletal muscle after strenuous exercise by high-fat diet
      mice.
AB  - PURPOSE: The purpose of this study was to investigate whether moderate exercise
      and quercetin intake with a low fat diet contribute to inflammatory cytokine
      production, mitochondrial biogenesis, and lipid metabolism in skeletal muscle
      after strenuous exercise by high-fat diet mice. METHODS: Male C57BL/6 mice were
      randomly divided into four groups: (1) High-fat for 12 weeks and low-fat diet
      control (C; n = 6); (2) high-fat diet for 12 weeks and low-fat diet with
      quercetin (Q; n = 4); (3) high-fat diet for 12 weeks and low-fat diet with
      exercise (E; n = 4); or (4) high-fat diet for 12 weeks and low-fat diet with
      exercise and quercetin (EQ; n = 5). Quercetin (10 mg/kg) was administered once
      per day, 5 day/week for 8 weeks. Exercise training was performed at moderate
      intensity for 8 weeks, 5 days/week for 30-60 min/day. Mice were subjected to a
      strenuous exercise bout of 60 min at a speed of 25 m/min (VO2 max 85%) conducted
      as an exercise-induced fatigue just before sacrifice. RESULTS: As results, body
      weights were significantly different among the groups. Exercise training
      significantly reduced inflammatory cytokines after strenuous exercise in skeletal
      muscle of high-fat diet mice. Exercise training increased Tfam mRNA in the soleus
      muscle after strenuous exercise. Exercise training significantly decreased
      lipogenesis markers in skeletal muscle of obese mice after strenuous exercise.
      Moderate exercise significantly increased lipolysis markers in the tibialis
      anterior muscle. CONCLUSION: These findings suggest that exercise training
      reduced inflammatory cytokine levels and improved mitochondrial biogenesis and
      lipid metabolism. However quercetin supplementation did not affect these
      parameters. Thus, long-term moderate exercise training has positive effects on
      obesity.

PMID- 25566440
TI  - Effects of combined exercise on cardiovascular risk factors and serum BDNF level
      in mid-aged women.
AB  - PURPOSE: The purposes of this study is first to examine a positive effect of long
      term combined exercise including aerobic and resistance exercise on increasing
      level of serum BDNF, and investigate how aerobic exercise is related to improving
      BDNF circulation and resistance exercise improves fat oxidation in mid-aged
      women. METHODS: Initially, 30 mid-aged women, according to their exercise
      preference, was randomly assigned as a non-exercise group (n=7, control group;
      CG) and exercise group (n=23). Then, 23 exercise participants were divided by
      aerobic exercise group (n=15, AEG) and combination of aerobic and resistance
      exercise group (n=8, CEG). Prior to the experiment, all participants'maximal
      oxygen uptake (VO2max), body composition, and blood factors were measured.
      Changes (Delta delta value) in body composition, fitness level, and serum BDNF
      level of the different groups were tested through one way ANOVA. RESULTS: For AEG
      and CG after 24 weeks, VO2max and high-density lipoprotein cholesterol (HDL-C)
      were significantly increased. During this period, CEG had significant increase in
      muscular strength and decrease in triglyceride (TG) total cholesterol (TC)/HDL-C
      (p=0.013). Continuously, serum BDNF concentration of both AEG and CEG was
      significantly increased (F=6.328, p=0.001) compared to CG. There, however, was no
      significant between-group difference. CONCLUSION: Although there was no
      difference in serum BDNF level between AEG and CEG, we confirmed that CEG may
      have a possibility of positive changes in increase of serum BDNF level in mid
      aged women.

PMID- 25566442
TI  - Exercise training is more effective than resveratrol supplementation on
      alleviation of inflammation in peritoneal macrophages of high fat diet mice.
AB  - PURPOSE: This study investigated the effect of exercise training and resveratrol
      supplementation with low fat diet on proinflammatory profiles by
      Lipopolysaccharide (LPS)-stimulation in peritoneal macrophage of high fat diet
      mice. METHODS: To accomplish the purpose of this study, C57BL/6 male mice were
      fed high fat diet (45% fat diet) for 8 weeks. Then these mice were divided into 3
      groups; HLC (high fat diet and low fat diet for 8 weeks as the control, n=10),
      HLR (high fat diet and low fat diet for 8 weeks with resveratrol supplementation,
      n=10). HLE (high fat diet and low fat diet for 8 weeks with moderate exercise
      training, n=10). Resveratrol (10 mg/kg) was administrated once a day, 5 days/week
      for 8 weeks. Exercise training was performed for 8 weeks on a treadmill running
      for 30-60 min/day at 10-22 m/min, 0% grade, 5 days/week. After exercise training,
      all the peritoneal macrophage was collected and LPS (0, 0.5, 1.0 MUg/ml) were
      used to stimulate the cells. Then peritoneal macrophage TNF-alpha, IL-6, MCP-1,
      IL12p70, IFN-gamma, IL-10 were measured by BD cytometric bead array mouse
      inflammation kit. RESULTS: As a result, body weight and total cholesterol were
      significantly reduced in HLE compared with HLC (p<.05). Also, TNF-alpha and MCP-1
      were decreased in HLE compared with HLC (p<.05) by LPS-stimulation (0, 0.5, 1.0
      MUg/ml) and IL-6, IL-12p70 and IFN-r were decreased in HLE compared with HLC
      (p<.05) by LPS-stimulation (1.0 MUg/ml). But resveratrol supplementation did not
      affect the result. CONCLUSION: These findings suggest that exercise training has
      beneficial effects on body weight, total cholesterol, peritoneal macrophage and
      proinflammatory cytokine in high fat diet mice.

PMID- 25566441
TI  - The effects of a single bout pilates exercise on mRNA expression of bone
      metabolic cytokines in osteopenia women.
AB  - PURPOSE: The purpose of this study was to examine the effect of a single bout
      pilates exercise on mRNA expression of bone metabolic cytokines in elderly
      osteopenia women. METHODS: We selected 11 people of elderly osteopenia women and
      loaded a single bout pilates exercise about RPE 10-14 level. The blood samples
      were collected before, immediately after and 60 minute after pilates exercise,
      then examined calcium metabolic markers in serum and extracted peripheral blood
      mononuclear cell (PBMC) from whole blood and confirmed mRNA expression of bone
      metabolic cytokines from PBMC. To clarify the changes during exercise, we
      designed repeated measure ANOVA as the control group to perform blood sampling
      without exercise. RESULTS: As a result, serum P showed significant interaction
      effect between group and time (p<.001), the pilates exercise group decreased
      about 9% at immediately after exercise and 13% during recovery after exercise
      (p<.05), while the control group showed a tendency to increase. Serum CK also
      showed a significant interaction between group and time (p<.05), the pilates
      group significantly increased at immediately after exercise and during recovery
      after exercise (p<.05) but the control group didn't have changes. TNF-alpha and
      IL-6 mRNA expression in PBMC was significantly increased in the pilates group
      (p<.01, p<.05), although INF-gamma mRNA expression didn't show statistically
      significant difference, it tended to increase in the pilates group (NS).
      CONCLUSION: These results suggested that a single bout pilates exercise of
      elderly osteopenia women cause hypophosphatemia with temporary muscle damage, and
      it leading high turnover bone metabolic state with to activate both of bone
      formation and bone resorption.

PMID- 25566443
TI  - Effects of treadmill exercise on brain insulin signaling and beta-amyloid in
      intracerebroventricular streptozotocin induced-memory impairment in rats.
AB  - PURPOSE: The purpose of the study is to explore effect of 6 weeks treadmill
      exercise on brain insulin signaling and beta-amyloid(Abeta). METHODS: The rat
      model of Alzheimer's disease(AD) used in the present study was induced by the
      intracerebroventricular(ICV) streptozotocin(STZ). To produce the model of animal
      with AD, STZ(1.5mg/kg) was injected to a cerebral ventricle of both cerebrums of
      Sprague-Dawley rat(20 weeks). The experimental animals were divided into ICV
      Sham(n=7), ICV-STZ CON(n=7), ICV-STZ EXE(n=7). Treadmill exercise was done for 30
      min a day, 5 days a week for 6 weeks. Passive avoidance task was carried out
      before and after treadmill exercise. RESULTS: The results of this study show that
      treadmill exercise activated Protein kinase B(AKT)/ Glycogen synthase kinase
      3alpha (GSK3alpha), possibly via activation of insulin receptor(IR) and insulin
      receptor substrate(IRS) and reduced Abeta in the brain of ICV-STZ rats. More
      interestingly, treadmill exercise improved cognitive function of ICV-STZ rats.
      Finally, physical exercise or physical activity gave positive influences on brain
      insulin signaling pathway. CONCLUSION: Therefore, treadmill exercise can be
      applied to improve AD as preventive and therapeutic method.

PMID- 25566444
TI  - Chronic exercise improves repeated restraint stress-induced anxiety and
      depression through 5HT1A receptor and cAMP signaling in hippocampus.
AB  - PURPOSE: Mood disorders such as anxiety and depression are prevalent psychiatric
      illness, but the role of 5HT1A in the anti-depressive effects of exercise has
      been rarely known yet. We investigated whether long-term exercise affected a
      depressive-like behavior and a hippocampal 5HT1A receptor-mediated cAMP/PKA/CREB
      signaling in depression mice model. METHODS: To induce depressive behaviors, mice
      were subjected to 14 consecutive days of restraint stress (2 hours/day).
      Depression-like behaviors were measured by forced swimming test (TST), and
      anxiety-like behavior was assessed by elevated plus maze (EPM). Treadmill
      exercise was performed with 19 m/min for 60 min/day, 5 days/week from weeks 0 to
      8. Restraint stress was started at week 6 week and ended at week 8. To elucidate
      the role of 5HT1A in depression, the immunoreactivities of 5HT1A were detected in
      hippocampus using immunohistochemical technique. RESULTS: Chronic/repeated
      restraint stress induced behavioral anxiety and depression, such as reduced time
      and entries in open arms in EPM and enhanced immobility time in FST. These
      anxiety and depressive behaviors were ameliorated by chronic exercise. Also,
      these behavioral changes were concurrent with the deficit of 5HT1A and
      cAMP/PKA/CREB cascade in hippocampus, which was coped with chronic exercise.
      CONCLUSION: These results suggest that chronic exercise may improve the
      disturbance of hippocampal 5HT1A-regulated cAMP/PKA/CREB signaling in a depressed
      brain, thereby exerting an antidepressive action.

PMID- 25566445
TI  - Endurance exercise training inhibits neointimal formation via enhancement of
      FOXOs expression in balloon-induced atherosclerosis rat model.
AB  - PURPOSE: This study investigated the effect of endurance exercise on neointimal
      formation, endothelial-dependant relaxation and FOXO expression in balloon
      induced carotid arteries of rats. METHODS: Male SD(Sprague-Dawley) rats of 8
      weeks ages were randomly divided into 3 groups; Sham-operated control (SO, n=10),
      Balloon-induced control (BIC, n=10), and Balloon-induced exercise (BIE, n=10).
      Endurance exercise training was performed on treadmill (18 m/min, 0% grade, 60
      min/day, 5 days/week, 4 weeks). RESULTS: Body weight is significantly reduced in
      BIE compared with BIC. Neointiaml formation in BIC was significantly higher than
      SO, but it was significantly recovered in BIE compared with BIC. Endothelial
      dependent relaxation in BIC was significantly lower than SO, but it was
      significantly recovered in BIE compared with BIC and expression of FOXO1 and
      FOXO3a also were significantly increased BIE compared with BIC. CONCLUSION: These
      data suggest that endurance exercise inhibits neointimal formation and
      endothelial-dependent relaxation via FOXO expression in balloon-induce
      atherosclerosis rat model.

PMID- 25566446
TI  - Changes of bone metabolism based on the different interventions with exercise
      type or additional intake material in ovariectomized rats.
AB  - PURPOSE: This study is aimed at providing clear guidance on treatment and
      prevention of osteoporosis by comparing and analyzing some well-known methods out
      of drug and exercise therapies. METHODS: For this purpose, eight-week experiments
      (drug therapy and exercise therapy) were carried out by using rats whose
      menopause was induced by the removal of an ovary. In the treatment of the drug
      therapy, the effects of soy protein, one of the well-known alendronate and
      estrogen replacement therapy, were compared and analyzed. In the treatment of the
      exercise therapy, endurance exercise using a treadmill and resistance exercise
      through climbing a special cage were compared and analyzed. Based on these
      results, this study will be able to suggest the most appropriate way to deal with
      osteoporosis which requires long-term treatment. Sixty eight-week-old Sprague
      Dawley female rats had a week to adapt to the new environment. After that, they
      were randomly divided into four groups (Sham-Sedentary; SS, ovariectomized
      control; OC, ovariectomized-soy protein; OS: ovariectomized-alendronate; OA,
      ovariectomized-endurance exercise; OE, ovariectomized-resistance exercise; OR)
      before having an operation for the removal of an ovary. After surgery, the rats
      convalesced for a week. Alendronate (0.4mg / kg of body weight) and isoflavones
      (200g / 1 kg of feed) were given to two groups respectively for eight weeks. The
      rats in the other two groups performed resistance exercise (climbing) and
      endurance exercise (20 m/min; 60min/day) five days a week for eight weeks.
      RESULTS: Ovariectomy increased the body weight and body fat like menopause did.
      Soy protein and alendronate intake for eight weeks had no effect on body weight
      but reduced the body fat increased by ovariectomy to the level of the SS group.
      The menopause induced by ovariectomy did not affect total bone density and bone
      mass as well as bone density in specific areas of the body. Soy protein and
      alendronate intake for eight weeks did not significantly affect them either.
      However, the eight-week treatment with soy protein and alendronate significantly
      reduced the level of osteocalcin in blood. Resistance exercise more noticeably
      increased body weight and bone mass than running on the low-intensity treadmill
      but serum osteocalcin levels were notably increased in both cases. CONCLUSION:
      These results show that soy protein which is natural produce and low-intensity,
      regular endurance exercise also have an effect on the treatment and prevention of
      osteoporosis caused by menopause.

PMID- 25566448
TI  - The effects of different exercise modes for preventing endothelial dysfunction of
      arteries and bone loss in ovariectomized rats.
AB  - PURPOSE: Several epidemiological studies have demonstrated that there are
      positive correlations between vascular disorders and bone loss in postmenopausal
      women. The aim of the present study was to examine the effect of different types
      of exercise (e.g., climbing and swimming) for preventing endothelial dysfunction
      of arteries and bone loss in ovariectomized rats. METHODS: Twenty Sprague-Dawley
      female rats were randomly divided into three groups: ovariectomy (OVX) plus
      treatment with vitamin D3 and nicotine (VDN) (control rats [Con], n = 7), which
      is an animal model for endothelial dysfunction and bone loss; voluntary climbing
      resistance exercise with OVX plus VDN (climbing rats [Clim], n = 6), and swimming
      exercise with OVX plus VDN (swimming rats [Swim], n = 7). The period of exercise
      training was 8 weeks. RESULTS: The endothelin-1 (ET-1) protein levels were
      significantly lower in the Clim and Swim groups than in the Con. The endothelial
      nitric oxide synthase protein levels were significantly higher in the Swim group
      than in the Con, but they did not differ between the Clim and Con groups. The
      cortical bone mineral density in the tibia and breaking energy of the femur were
      significantly higher in the Clim group than in the Con, but this positive effect
      was not seen in the Swim group. CONCLUSION: Voluntary climbing exercise decreased
      arterial ET-1 protein levels and prevented bone loss in a postmenopause-model rat
      combining OVX and VDN. Conversely, swimming suppressed endothelial dysfunction of
      the arteries but did not prevent bone loss. Thus, the type of exercise should be
      cautiously chosen for enhancing vascular function and bone status, especially in
      females after menopause.

PMID- 25566449
TI  - Silkworm pupae powder ingestion increases fat metabolism in swim-trained rats.
AB  - PURPOSE: Many researchers are trying to solve the metabolic syndrome by utilizing
      a variety of nutritional control and exercise. Of those, silkworm pupae peptides
      are known to inhibit the synthesis of fat. Therefore, we examine the effect of
      fat metabolism by supplying silkworm pupae (SP) for 5-week in swim-trained rats.
      METHODS: Animals were divided into four groups as a group (n = 32) fed a normal
      diet (CO) with exercise training (CE); a group fed a silkworm pupa diet (SPC)
      with an exercise training (SPE), respectively. RESULTS: Abdominal fat pads
      (abdominal and epididymal) weight were lowest in SPE. The serum triglyceride,
      total cholesterol concentrations were lower in the SP and the SPE. HDL
      cholesterol, however, was not different between groups. Liver AMPK (AMP-activated
      protein kinase) was increased in the CE and the SPE. Liver PPAR-alpha (Peroxisome
      proliferator-activated receptor alpha) was increased in the SPC and SPE. L-FABP
      (liver fatty acids binding protein) was increased by SP ingestion. Liver CPT-1
      (carnitine palmitoyltransferase-1) protein expression was increased by exercise
      training only. CONCLUSION: In the present study showed that the silkworm pupae
      intake and/or swimming exercise training activates fat metabolism to reduce the
      concentration of serum lipids. Thus, the silkworm pupae intake leads to a
      reduction in fat storage, this is considered to be effective in the inhibition of
      the metabolic syndrome.

PMID- 25566447
TI  - Moderate intensity exercise inhibits macrophage infiltration and attenuates
      adipocyte inflammation in ovariectomized rats.
AB  - PURPOSE: The purpose of this study was to investigate the effects of the
      different endurance exercise intensities on the macrophage infiltration and
      adipocyte inflammation of ovariectomized rats. METHODS: 24 female SD rats (6
      weeks old) were randomly assigned to sham control (SC; n=6), ovariectomized
      control (OC; n=6), ovariectomized low intensity exercise (OL; n=6), and
      ovariectomized moderate intensity exercise (OM; n=6) groups. The two training
      groups ran for 60 min/day, 5 times/ week at 18 and 26m/min for 16 weeks. Twenty
      four hours after the last exercise session, rats were sacrified, and epididymal
      pads were analyzed. F4/80 and IL-6 expressions were evaluated by western
      blotting. ICAM-1, VCAM-1 TLR4, TNF-alpha, and MCP-1 mRNA expressions were
      evaluated by RT-PCR. RESULTS: In comparison with OC group, OM group showed
      significantly lower body weight gain and adipose tissue mass. Also, OM group
      markedly inhibited F4/80 expression, adhesion molecule (ICAM-1, VCAM-1) and pro
      inflammatory cytokines (TLR4, TNF-alpha, MCP-1) mRNA expressions in adipose
      tissue. In contrast, OL group partially prevented body weight gain while other
      examined parameter were unaffected by low intensity exercise training.
      CONCLUSION: The results of this study suggest that OM group inhibits visceral
      macrophage infiltration by suppressing the adhesion molecules. It may also
      attenuate cytokine production in the adipose tissue by repressing the TLR4
      mediated pro-inflammatory signaling cascades in ovariectomized rats.

PMID- 25566451
TI  - Changes in alphaB-crystallin, tubulin, and MHC isoforms by hindlimb unloading
      show different expression patterns in various hindlimb muscles.
AB  - PURPOSE: alphaB-crystallin is a small heat shock protein that acts as a molecular
      chaperone under various stress conditions. Microtubules, which consist of
      tubulin, are related to maintain the intracellular organelles and cellular
      morphology. These two proteins have been shown to be related to the properties of
      different types of myofibers based on their contractile properties. The response
      of these proteins during muscular atrophy, which induces a myofibril component
      change, is not clearly understood. METHODS: We performed 15 days of hindlimb
      unloading on rats to investigate the transitions of these proteins by analyzing
      their absolute quantities. Protein contents were analyzed in the soleus,
      plantaris, and gastrocnemius muscles of the unloading and control groups (N = 6).
      RESULTS: All three muscles were significantly atrophied by hindlimb unloading (P
      < 0.01): soleus (47.5%), plantaris (16.3%), and gastrocnemius (21.3%) compared to
      each control group. alphaB-crystallin was significantly reduced in all three
      examined unloaded hindlimb muscles compared to controls (P < 0.01) during the
      transition of the myosin heavy chain to fast twitch muscles. alpha-Tubulin
      responded only in the unloaded soleus muscle. Muscle atrophy induced the
      reduction of alphaB-crystallin and alpha-tubulin expressions in plantar flexor
      muscles with a shift to the fast muscle fiber compared to the control.
      CONCLUSION: The novel finding of this study is that both proteins, alphaB
      crystallin and alpha-tubulin, were downregulated in slow muscles (P < 0.01);
      However, alpha-tubulin was not significantly reduced compared to the control in
      fast muscles (P < 0.01).

PMID- 25566450
TI  - Effects of detraining on motor unit potential area, muscle function and physical
      performance based on CNTF gene polymorphism.
AB  - PURPOSE: The purpose of this study was to identify the effect of detraining on
      motor unit potential area (SMUP), muscular function and physical performance,
      according to CNTF gene polymorphism. METHODS: For this study, GG (normal
      homozygote, n = 8) group and GA + AA (mutation heterozygote and homozygote, n =
      10) group were divided by CNTF gene polymorphism and both groups were performed
      detraining for 4 weeks. The data was analyzed by two-way repeated measures ANOVA
      for verifying the differences between two groups and interaction using SPSS (ver.
      20.0) statistical program. RESULTS: The results were as follows. First, changes
      in body composition were measured but there was no significant interaction effect
      between time and group. Seconds, changes in SMUP were measured by SEMG.
      Interaction effect between time and group was found lateral vastus during
      isokinetic exercise of 180 degrees /sec (p < .05). Third, changes in isokinetic
      muscle strength of 60 degrees /sec and 180 degrees /sec were measured but there
      was no significant interaction effect. Fourth, significant statistical
      differences were not showed changes of sports performance after detraining.
      CONCLUSION: In conclusion, there were no significantly differences between GG and
      GA + AA group after detraining, therefore, further study will be considered a
      matter in various its interventions such as serum levels of CNTF and changes in
      receptors and muscle fiber types.

PMID- 25566453
TI  - Exercise Training suppresses vascular fibrosis in aging obesity induced rats.
AB  - PURPOSE: The aim of this study was to investigate the effects of exercise
      training (ET) on vascular fibrosis in aging model rats with diet-induced obesity.
      METHODS: Twenty-four male Sprague-Dawley rats were divided into 3 groups: Aging
      control (A-C), A-C with high fat diet (AHF), AHF with ET (AHF + ET). Aging was
      induced by D-galactose (D-gal) and obesity was induced by HFD (60% fat) for 9
      weeks. The experimental rats performed swimming (60 min/day, 5 days/week) for 8
      weeks. All rat aorta samples were harvested for RT-PCR and morphologic analyses.
      RESULTS: The exercise training significantly decreased levels of AT-1, TGF-beta
      and Coll-1 gene expression compared to AHF group. The AHF + ET group showed a
      reduced collagen accumulation in the aorta media compared to AHF group.
      CONCLUSION: These results suggest that ET could protect the aging obesity aorta
      against down-regulation of fibrotic factors (AT-1, TGF-beta and Coll-1 gene) and
      fibrosis by inhibition of collagen accumulation in the aorta media.

PMID- 25566452
TI  - Differences of energy intake and energy expenditure of elite Taekwondo players
      receiving summer vs. winter intensive training.
AB  - PURPOSE: This study aimed to evaluate the energy expenditure and energy intake as
      an experiment of energy balance of elite Taekwondo players receiving summer vs.
      winter intensive training. METHODS: The summer training group (STG, n = 15) and
      the winter training group (WTG, n = 18) wore an accelerometer for the measurement
      of energy expenditure and maintained a daily dietary record for measurement of
      energy intake, for seven consecutive days during summer or winter intensive
      training. RESULTS: The total energy expenditure (TEE) (834.1 kcal, p < .001), the
      total counts (1,867 counts, p = .038), and the energy expenditure during moderate
      (384.6 kcal, p < .001) and vigorous activity (351.8 kcal, p < .001) were
      significantly lower in the STG than in the WTG. On the other hand, the
      macronutrient intake showed that intake of energy (902.7 kcal, p < .001),
      carbohydrates (82.6g, p < .001), and protein (93.9g, p < .001) in the STG were
      significantly lower than those of the WTG. When comparing TEE and total energy
      intake, the STG consumed 902.7 kcal less as energy than the WTG, while the STG
      performed 834.1 kcal more as TEE than that of the WTG. CONCLUSION: In conclusion,
      both of the summer and winter intensive training are not proper for energy
      balance condition. Therefore, to promote the optimal energy balance during the
      summer or winter intensive training period, a training and sports nutrition
      program based on the amount of energy expenditure and energy intake for Taekwondo
      players should be considered.

PMID- 25566454
TI  - Effects of low calorie diet-induced weight loss on post-exercise heart rate
      recovery in obese men.
AB  - PURPOSE: Heart Rate Recovery (HRR) after maximum exercise is a reactivation
      function of vagus nerve and an independent risk factor that predicts
      cardiovascular disease and mortality. Weight loss obtained through dietary
      programs has been employed as a therapy to reduce risks of cardiovascular disease
      and obesity. METHODS: Eighteen subjects of middle aged obese men (age 44.8 +/-
      1.6 yrs, BMI 29.7 +/- 0.5 kg/m(2)) were selected for this study. As a weight loss
      direction, the nutritional direction of low-calorie diet mainly consisted of
      carbohydrate, protein, and fat has been conducted for 3 months. Blood pressure
      was measured after overnight fasting, and blood samples were collected from the
      antecubital vein before and after weight loss program. All the pre- and post
      exercise 'HRR decay constant's were assessed by using values of HRR (heart
      recovery rate; 2 minutes) and HR measured after reached to the maximal oxygen
      uptake (VO2max) exploited the bicycle ergometer. RESULTS: After the completion of
      weight loss program, body weight and BMI were significantly decreased, but the
      Heart Rate (HR) after maximum exercise and in steady state were not changed
      significantly (p > 0.05). The post-exercise HRR after the weight loss did not
      show significant changes in perspectives of 30 seconds (-16.6 +/- 2.3 to -20.2 +/
      2.1 beats/min, p > 0.05) and 60 seconds (-33.5 +/- 3.4 to -34.6 +/- 2.8
      beats/min, p > 0.05) respectively but in perspectives of 90 seconds (-40.9 +/-
      2.6 to -48.1 +/- 3.1 beats/min, p < 0.05) and 120 seconds (-48.6 +/- 2.6 to -54.3
      +/- 3.5 beats/min, p < 0.05), they were decreased significantly. Pre-'HRR decay
      constant's of 0.294 +/- 0.02 %/second were significantly increased to post-values
      of 0.342 +/- 0.03 %/second (p = 0.026). Changes in 'HRR decay constant' were
      significantly correlated with changes in blood glucose (r = -0.471, p < 0.05) and
      maximal oxygen consumption (VO2max, r = 0.505, p < 0.05) respectively.
      CONCLUSIONS: The low-calorie diet directed to obese middle aged men for 3 months
      significantly improved the HRR after maximum exercise, and this improvement in
      cardiovascular autonomic nerve system was estimated to be involved with
      improvements in blood glucose and maximal oxygen consumption.

PMID- 25566455
TI  - Verification of efficacy as an ergogenic aid and safety in doping of sibjeondaebo
      tang.
AB  - PURPOSE: Various kinds of food substances from all over the world have been
      proposed to use as ergogenic aids for the additional improvement of exercise
      performance especially in athletes. Herb medicine which usually being applied for
      the cure of disease is used as a performance booster in several far eastern
      countries including Korea. Many scientists and coaches have asked very objective
      verifications on the reality of herb medicines practically used but never been
      scientifically elucidated well enough. In addition to the possibility as an
      ergogenic aid, the safety in doping is the critical factor to be examined
      thoroughly. In this study, Sibjeondaebo-Tang, a leading popular prescribed herb
      medicine in Korea, was examined. METHODS: After the intake of Sibjeondaebo-Tang,
      its effects on VO2max, recovery from fatigue, and doping safety through the
      official process as WADA suggested. Six volunteered male Taekwondo Pumsae players
      were subjected in a repeatedly examined protocol. RESULTS: First of all, every
      subjects showed 'negative' in doping test, and the treatment did not show any
      significant improvement on VO2max even though there was a significant decrease in
      blood lactate level on a step test. CONCLUSION: In conclusion, Sibjeondaebo-Tang
      may have some limited effects as a fatigue delayer and the use of it showed safe
      to doping test with the strict limitation as the way in this study. So we should
      abstain from the over-interpreted application of the results so far.

PMID- 25566456
TI  - The effects of landed and aquatic treadmill walking at moderate intensity on
      heart rate, energy expenditure and catecholamine.
AB  - PURPOSE: The present study was to examine whether or not the appropriate exercise
      intensity of water-walking could be accurately prescribed by land-based walking
      speed. METHODS: Using a crossover design, nine healthy male college students
      completed bouts of walking for thirty minutes at 100m/min, 50m/min, respectively,
      on land and water treadmills. Heart rate (HR), ratings of perceived exertion
      (RPE), energy expenditure, blood lactic acid and catecholamine concentration were
      measured. Two-way repeated measured ANOVA was used with the SPSS program for data
      analysis. RESULTS: HR (P < 0.001), RPE (P < 0.001), energy expenditure (P <
      0.001), blood lactic acid (P < 0.001) and epinephrine concentration (P < 0.05)
      were significantly increased during walking both in water and on land. The change
      of HR was significantly lower at 50min/m in water than 100min/m on land (P <
      0.01). There were no significant interaction effects for RPE, energy expenditure,
      blood lactic acid and catecholamine concentration, but these variables were
      slightly lower in water than on land. These results indicated that the use of
      land walking speed-based prescriptive norms would underestimate the physiological
      cost in water walking at the moderate intensity. CONCLUSION: Therefore,
      approximately two-half of the speed would be needed to walk in water in order to
      obtain the same level of physiological load as during treadmill walking at the
      moderate intensity.

PMID- 25566457
TI  - Genetic associations of body composition, flexibility and injury risk with ACE,
      ACTN3 and COL5A1 polymorphisms in Korean ballerinas.
AB  - PURPOSE: The purpose of this study was to exam the association of body
      composition, flexibility, and injury risk to genetic polymorphisms including ACE
      ID, ACTN3 RX, and COL5A1 polymorphisms in ballet dancers in Korea. METHODS: For
      the purpose of this study, elite ballerinas (n = 97) and normal female adults (n
      = 203) aged 18 to 39 were recruited and these participants were tested for body
      weight, height, body fat, fat free mass, flexibility, injury risks on the joints
      and gene polymorphisms (ACE, ACTN3, COL5A1 polymorphism). RESULTS: As results,
      the ACE DD genotype in ballerinas was associated with higher body fat and
      percentage of body fat than the ACE II and ID genotypes (p < 0.05). In the study
      on the ACTN3 polymorphism and ballerinas, the XX genotype in ballerinas had lower
      body weight and lower fat-free mass than the RR and RX genotype (p < 0.005).
      Also, the means of sit and reach test for flexibility was lower in the ACTN3 XX
      genotype of ballerinas than the RR and RX genotype of ballerinas (p < 0.05).
      Among the sports injuries, the ankle injury of the XX-genotyped ballerinas was in
      significantly more prevalence than the RR and XX-genotyped ballerinas (p < 0.05).
      According to the odd ratio analysis, XX-genotyped ballerinas have the injury risk
      on the ankle about 4.7 (95% CI: 1.6~13.4, p < 0.05) times more than the RR and RX
      genotyped ballerinas. Meanwhile, the COL5A1 polymorphism in ballerinas has no
      association with any factors including flexibility and injury risks. CONCLUSION:
      In conclusion, ACE polymorphism and ACTN3 polymorphism were associated with
      ballerinas' performance capacity; COL5A1 was not associated with any factors of
      performance of Ballerinas. The results suggested that the ACE DD genotype is
      associated with high body fat, the ACTN3 XX genotype is associated with low fat
      free mass, low flexibility, and higher risk of ankle-joint injury.

PMID- 25566458
TI  - Effects of active drinking practices on fluid consumption and sweat rate while
      exercising in a hot environment.
AB  - PURPOSE: To examine the effects of active drinking practices on fluid consumption
      and sweat rate while exercising in a hot environment. METHODS: Nine men completed
      two experiments. Each consisted of 3 phases: pre-testing (pre), training period,
      and post-testing (post). During testing, the subjects ran on a treadmill at a
      moderate intensity for 90 min at 39 +/- 1C followed by a 3-h recovery. They drank
      ad libitum. During training, they ran for 90 min for 7 days while either drinking
      actively (AH, 150% of weight loss) or passively (PH, 50% of weight loss).
      RESULTS: The actual volume consumed in training was three times greater during AH
      than during PH. In post during AH, the volume of drinking was two times greater
      than pre (1592 +/- 953 and 855 +/- 551 mL, respectively; p < 0.05). No difference
      in volume consumption during PH between pre and post was found. The sweat loss
      during exercise was greater in post (1377 +/- 956 mL) than in pre (558 +/- 642
      mL) during AH (p < 0.05), but not during PH. Rectal temperature and heart rate
      decreased after training. Serum osmolality following exercise were not different
      than the baseline or between the conditions. CONCLUSION: Active drinking
      practices while exercising in a hot environment induced greater voluntary fluid
      intake and sweat loss.

PMID- 25566459
TI  - The effect of treadmill exercise on inflammatory responses in rat model of
      streptozotocin-induced experimental dementia of Alzheimer's type.
AB  - PURPOSE: The aim of this study was to investigate the effect of treadmill
      exercise on inflammatory response in streptozotocin (STZ)-induced animal model of
      Alzheimer's disease (AD). METHODS: To induce the animal model of AD, Sprague
      Dawley rats were injected into intracerebroventricular (ICV) injection with 1.5
      mg/kg of STZ. Rats were divided into three groups as Sham-con group (n = 7), STZ
      con group (n = 7) and STZ-exe group (n = 7). Exercise group ran on the treadmill
      for 30 min/day, 5 days/week during 6 weeks. RESULTS: The results of this study
      were as follows: First, STZ-exe group was improved on cognitive function when
      compared to STZ-con group in water maze test. Second, STZ-exe group help reduce
      the expression level of amyloid-beta (Abeta). In addition, Toll-like receptors-4
      (TLR4), Nuclear factor-kB (NF-kB), Tumor necrosis factor-alpha (TNF-alpha) and
      Interleukin-1alpha (IL-1alpha) level of STZ-exe group was significantly decreased
      when compared to STZ-con group. CONCLUSION: These results show that treadmill
      exercise had positive effect on cognitive function and reduced inflammatory
      response in STZ-induced animal model of AD.

PMID- 25566461
TI  - Effects of vitamin D supplementation and circuit training on indices of obesity
      and insulin resistance in T2D and vitamin D deficient elderly women.
AB  - PURPOSE: The purpose of this study was to investigate the effects of vitamin D
      supplementation and circuit training on body composition, abdominal fat, blood
      lipids, and insulin resistance in T2D and vitamin D deficient elderly women.
      METHODS: Fifty-two elderly women were randomly assigned to either the vitamin D
      supplementation with circuit training group (D+T: n = 15), the circuit training
      group (T: n = 13), the vitamin D supplementation group (D: n = 11), or the
      control group (CON: n = 13). The subjects in D took vitamin D supplements at
      1,200 IU per day for 12 weeks; the subjects in T exercised 3 to 4 times per week,
      25 to 40 minutes per session for 12 weeks; and the subjects in D+T participated
      in both treatments. Subjects in CON were asked to maintain normal daily life
      pattern for the duration of the study. Body composition, abdominal fat, blood
      lipids, and surrogate indices for insulin resistance were measured at pre- and
      post-test and the data were compared among the four groups and between two tests
      by utilizing two-way ANOVA with repeated measures. The main results of the
      present study were as follows: RESULTS: 1) Body weight, fat mass, percent body
      fat, and BMI decreased significantly in T, whereas there were no significant
      changes in the variables in D and CON. Lean body mass showed no significant
      changes in all groups. 2) TFA and SFA decreased significantly in T, whereas there
      were no significant changes in the variables in D and CON. The other abdominal
      fat related variables showed no significant changes in all groups. 3) TC, TG, HDL
      C, and LDL-C showed improvements in T, whereas there were no significant changes
      in the variables in D and CON. 4) Fasting glucose, fasting insulin, and HOMA-IR
      tended to be lower in D+T. CONCLUSION: It was concluded that the 12 weeks of
      vitamin D supplementation and circuit training would have positive effects on
      abdominal fat and blood lipid profiles in T2D and vitamin D deficient elderly
      women. Vitamin D supplementation was especially effective when it was
      complemented with exercise training.

PMID- 25566460
TI  - Type 2 Diabetes: Endothelial dysfunction and Exercise.
AB  - PURPOSE: Vascular endothelial dysfunction is an early marker of atherosclerosis
      characterized by decreased nitric oxide bioavailability in the vascular
      endothelium and smooth muscle cells. Recently, some animal models and in vitro
      trials demonstrated that excessive superoxide production from mitochondria within
      vascular endothelial cells played a role in the pathogenesis of atherosclerosis
      in type 2 diabetes. This review provides a systematic assessment of the
      effectiveness of exercise to identify effective approaches to recognize diabetes
      risk and prevent progression to heart disease. METHODS: A systematic literature
      search was conducted to retrieve articles from 1979 to 2013 using the following
      databases: the MEDLINE, PubMed. Articles had to describe an intervention that
      physical activity and exercise to identify effective approaches to heart and
      vascular endothelium. RESULTS: Currently, physical activity and exercise
      guidelines aimed to improve cardiovascular health in patients with type 2
      diabetes are nonspecific. Benefit of aerobic exercise training on vascular
      endothelial function in type 2 diabetic patients is still controversial.
      CONCLUSION: it is necessary to demonstrate the mechanism of endothelial
      dysfunction from live human tissues so that we can provide more specific exercise
      training regimens to enhance cardiovascular health in type 2 diabetic patients.

PMID- 25566462
TI  - NAMPT regulates mitochondria biogenesis via NAD metabolism and calcium binding
      proteins during skeletal muscle contraction.
AB  - PURPOSE: The purpose of this study was to investigate the effect that muscle
      contraction induced NAD metabolism via NAMPT has on mitochondrial biogenesis.
      METHODS: Primary skeletal muscle cells were isolated from the gastrocnemius in
      C57BL/6 mice. The muscle cells were stimulated by electrical current at 1Hz for 3
      minutes in conditions of normal or NAD metabolism related inhibitor treatment.
      NAD/NADH level, Sirt1 and mitochondria biogenesis related signal factor's changes
      were examined in normal or NAD metabolism related inhibitor treated cells.
      RESULTS: Electrical stimulation (ES) induced muscle contractions significantly
      increased NAD/NADH levels, NAMPT inhibitor FK-866 inhibited ES-induced NAD
      formation, which caused SIRT1 expression and PGC-1alpha deacetylation to
      decrease. Moreover, NAMPT inhibition decreased mitochondrial biogenesis related
      mRNA, COX-1 and Tfam levels. Along with AMPK inhibitor, compound C decreases
      SIRT1 expression, PGC-1alpha deacetylation and muscle contraction induced
      mitochondrial biogenesis related mRNA increment. These results indicated that the
      AMPK-NAMPT signal is a key player for muscle contraction induced SIRT1 expression
      and PGC-1alpha deacetylation, which influences mitochondrial biogenesis.
      Inhibition of the AMPK upregulator, Camkkbeta, STO-609 decreased AMPK
      phosphorylation and SIRT1 expression but did not decrease PGC-1alpha
      deacetylation. However, CAMKII inhibition via AIP decreased PGC-1alpha
      deacetylation. CONCLUSION: In conclusion, the results indicate that NAMPT plays
      an important role in NAD metabolism and mitochondrial biogenesis. However,
      mitochondrial biogenesis is also controlled by different calcium binding protein
      signals including Camkkbeta and CAMKII. [Keyword] Muscle contraction, NAD
      metabolism, SIRT1, PGC-1 alpha, mitochondria biogenesis.

PMID- 25566463
TI  - The effects of pilates exercise on lipid metabolism and inflammatory cytokines
      mRNA expression in female undergraduates.
AB  - PURPOSE: The purpose of the study was to verify the effects of Pilates exercise
      by observing the impact of 8 weeks of Pilates exercise on lipid metabolism and
      inflammatory cytokine mRNA expression in female undergraduates in their 20s who
      had no prior experience in Pilates exercise and had not exercised in the previous
      6 months. METHODS: There were 18 subjects with no prior experience in Pilates
      exercise. The subjects were separated into the Pilates exercise group (n = 9) and
      the non-exercise control group (n = 9). The former performed Pilates exercise for
      60-70 minutes over 8 weeks with a gradual strength increase of 9-16 in the Rating
      of Perceived Exercise (RPE). The body composition, creatine kinase in the
      bloodstream and lipid metabolism (TC, LDL-C, HDL-C, TG) were measured before and
      after the experiment and Real-Time PCR was used to investigate the mRNA
      expression of the inflammatory cytokines IL-6 and TNF-?. RESULTS: The creatine
      kinase (CK) in the blood had significant differences between the groups. The test
      group showed significant increase compared to the control group after 8 weeks of
      Pilates exercise (p = 0.007). Lipid analysis showed that the level of high
      density lipoprotein cholesterol (HDL-C) was significantly different in the two
      groups (p = 0.049), with the Pilates exercise group exhibiting significantly
      higher levels compared to the control group. No significant differences were
      observed in the levels of total cholesterol (TC), low-density lipoprotein
      cholesterol (LDL-C) and triglyceride (TG). IL-6 mRNA expression did not show
      significant differences between the groups either. Timing and TNF-alpha mRNA
      expression showed significant effect in both the exercise and the control groups
      (p = 0.013) but no correlation. CONCLUSION: It was found from the study that
      Pilates exercise for 8 weeks affected CK expression (the muscle damage marker)
      and induced positive changes in the levels of high-density lipoprotein.

PMID- 25566464
TI  - Effect of walking exercise on abdominal fat, insulin resistance and serum
      cytokines in obese women.
AB  - PURPOSE: The purpose of the study was to investigate the effect of 12-week
      walking exercise on abdominal fat, insulin resistance and serum cytokines in
      obese women. METHODS: Following baseline measurements, obese women (N = 20) who
      met obesity criterion of BMI at 25 kg/m(2) or greater were randomly assigned to
      the control (n = 10) or exercise groups (n = 10). Women assigned to the exercise
      group participated in a walking exercise (with an intensity of 50-60% of
      predetermined VO(2)max, a frequency of 3 days per week and duration of 50-70
      minutes targeting 400 kcal of energy expenditure per session) for 12 weeks, while
      women assigned to the control group maintained their sedentary lifestyle. After
      the 12-week walking intervention, post-test measurements were conducted using the
      same procedure as the baseline measurement. Analyses of variance with repeated
      measures were used to evaluate any significant time by group interactions for the
      measured variables. RESULTS: With respect to body fat parameters, significant
      time-by-group interactions were found in the abdominal subcutaneous (p = < 0.001)
      and visceral adipose tissues (p = 0.011). The exercise group had significant
      reductions in both subcutaneous and visceral adiposity, and the control group had
      no significant changes in those parameters. Similarly, there were significant
      time by group interactions in fasting glucose (p = 0.008), HOMA-IR (p = 0.029),
      serum TNF-alpha (p = 0.027), and IL-6 (p = 0.048) such that the exercise group
      had significant reductions in those parameters, with no such significant changes
      found in the control group. The exercise group also had a significant increase in
      serum adiponectin (p = 0.002), whereas the control group had no significant
      change in the parameter. CONCLUSION: In summary, the current findings suggest
      that walking exercise can provide a safe and effective lifestyle strategy against
      abdominal obesity and serum insulin resistance markers in obese women.

PMID- 25566465
TI  - A survey of overweight, body shape perception and eating attitude of Korean
      female university students.
AB  - PURPOSE: We obtained basic data on a proper weight loss training program by
      considering the relationship between body mass index (BMI), the perception of
      appearance, and eating attitudes of Korean female university students. METHODS:
      The survey and anthropometry for the perception of appearance and eating
      attitudes were conducted targeting 657 female university students located in
      Seoul, Busan, Ulsan, Daejeon, Chungcheongnam-do, and Gangwon-do South Korea who
      were not specializing in physical education. RESULTS: The underweight group
      accounted for 21.16% of the population, the normal weight group comprised 69.71%,
      the overweight group was 6.09%, and the obese group accounted for 3.04%. The
      satisfaction rate of appearance was 56.16%, the dissatisfaction rate was 43.84%,
      and normal-weight students who were dissatisfied with their own appearance
      comprised 48.5%. The More obese students were more dissatisfied with their
      appearance. As a result of investigating eating attitudes, 37.75% of all subjects
      had a risk for an eating disorder, and 38.6% were normal weight but showed a risk
      for an eating disorder. More obese (BMI) subjects were at higher risk for an
      eating disorder. CONCLUSION: The BMIs of the Korean female university students
      were lower than those of European and American Caucasian women students, but the
      dissatisfaction of Korean female university students with their appearances was
      greater than that of European and American students, indicating that more Korean
      female university students were suffering from an eating disorder. It is
      predicted that the incidence of eating disorders, such as anorexia and bulimia,
      will rise in Korean women if there is no accurate understanding and measure to
      identify the high risk group for an eating disorder.

PMID- 25566466
TI  - Effects of exercise with or without light exposure on sleep quality and hormone
      reponses.
AB  - PURPOSE: The objectives of the present study were to determine the effect of sun
      exposure and aerobic exercise on quality of sleep and investigate sleep-related
      hormonal responses in college-aged males. METHODS: In this study, the cross-over
      design was utilized. The subjects (N = 10) without any physical problems or sleep
      disorders participated in the experimental performed 4 protocols in only sun
      exposure (for 30 minutes, EG1) protocol, only aerobic exercise (walking and
      jogging for 30 minutes, EG2) protocol, aerobic exercise with sun exposure (EG3)
      protocol, and control (no exercise and no sun exposure, EG4) protocol. Each
      protocol was 5 times per week with one-week break (wash-out period) between
      protocols to prevent the effects of the previous protocol. Total test period was
      should be 7 weeks (one week of protocol and one week of break). Before and after
      each aerobic exercise session, the subjects completed stretching to warm up for 5
      to 10 minutes. Surveys consisting of (bedtime, wake-up time, sleep onset latency,
      and (Pittsburgh Sleep Quality Index (PSQI) were obtained before the test and
      after each protocol. After each protocol, the following sleep-related hormonal
      responses were measured: blood concentrations of melatonin, cortisol,
      epinephrine, and norepinephrine. One-way ANOVA was used to determine differences
      between protocols. Statistical significance was set at p < 0.05. RESULTS: Bedtime
      of EG4 was significantly later than that of the EG1 or EG3. Wake-up time in the
      EG4 was significantly later than that of the EG1 or the EG3. Sleep onset latency
      in the EG4 was longer than that of the EG3. The quality of sleep in the EG4 was
      lower than that of the EG3. Sleep cycle in the EG4 was significantly shorter than
      that of the EG1. Blood melatonin concentrations of the EG3 was significantly
      higher than that of the EG4. There were no significant differences in blood
      concentrations of cortisol, epinephrine, or norepinephrine among protocols, with
      the order from the lowest to the highest values of EG1 < EG2 < EG3 < EG4.
      CONCLUSION: The present data found that EG1 and EG3 showed positive sleep-related
      hormonal responses, sleep habits, and quality of sleep, indicating that sun
      exposure or exercise with sun exposure may improve the physical status and
      quality of life.

PMID- 25566467
TI  - Antioxidant and antiapoptotic effects of pine needle powder ingestion and
      endurance training in high cholesterol-fed rats.
AB  - PURPOSE: Pine needle is a kind of medicinal plant ingested traditionally for a
      variety of purposes. Therefore, we examined the antioxidant and antiapoptotic
      capacities of pine needle ingestion in high cholesterol-fed and endurance
      exercise-trained rats. METHODS: Animals were divided into six groups as; CON:
      normal diet control group; EX: normal diet and exercise training group; HC: high
      cholesterol diet group; HCE: high cholesterol diet and exercise training group;
      HCP: high cholesterol and pine needle group; HCPE: high-cholesterol and pine
      needle diet with exercise training group, respectively. Each group consisted of
      seven Sprague-Dawley male rats. The swim-training groups, EX, HCE, and HCPE swam
      in the swim pool 60 min/d and 5 d/week for 5 weeks. During the rearing periods,
      freeze-dried pine needle powder mix with 5% of the high cholesterol diet was
      supplied to the HCP and HCPE groups. Gastrocnemius muscle was used as the
      skeletal muscle. Malondialdehyde (MDA), Mn-containing superoxide dismutase (Mn
      SOD), Cu, Zn containing superoxide dismutase (Cu,Zn-SOD), and glutathione
      peroxidase (GPx) were analyzed for their antioxidant capacities. Finally, p53,
      Bcl-2 (B-cell lymphoma 2), caspase-3 protein expression was analyzed to determine
      antiapoptotic ability. RESULTS: MDA showed low content in HCPE compared to the
      HC. Mn-SOD, Cu,Zn-SOD, and GPx protein expression was significantly increased by
      pine needle ingestion and/or exercise training. In addition, suppression of p53
      protein expression resulted in Bcl-2 increase followed by caspase-3 decrease
      with/without pine needle ingestion and exercise training. CONCLUSION: When
      exercise training in addition to pine needle powder ingestion may be a helpful
      nutritional regimen to athletes and exercisers.

PMID- 25566468
TI  - Combined influence of dietary restriction and treadmill running on MCP-1 and the
      expression of oxidative stress-related mRNA in the adipose tissue in obese mice.
AB  - PURPOSE: This study suggests that the negative effects of inflammation caused by
      obesity could be prevented through diet restriction and exercise. METHODS: In
      this study, 44 C57/BL6 male mice at about 4 weeks old (Orient bio, South Korea)
      were given a high fat diet for 5 weeks to make them obese. To help the mice lose
      weight, their dietary intake was limited and they were exercised on the treadmill
      for 8 weeks, and during that period, we analyzed the changes of MCP-1, ERK, Mn
      SOD, HIF-1, and NOX in epididymal adipose tissue. There ND control group and
      obese group with high fat diet (HFD), and it is divided into four groups; HFD-ND
      EX group, HFD-ND-nonEX group, HFD-DR-EX group and HFD-DR-nonEX group. RESULTS:
      During their progress, the mRNA expressions of HIF-1alpha and ERK2 decreased, as
      did the expression of MCP-1 contained in the nucleus by suppressing oxygen free
      radicals, which was observed after the exercise program. However, dietary
      restriction without exercise training triggered an increase in the mRNA
      expression of MCP-1. CONCLUSION: To put this in perspective, combining exercise
      and dietary intake restriction likely prevented an influx of macrophages by
      reducing the number of fat cells, whereas only dietary restriction was not
      effective against reducing inflammation.

PMID- 25566469
TI  - Effect of robotic-assisted gait training in patients with incomplete spinal cord
      injury.
AB  - OBJECTIVE: To determine the effect of robotic-assisted gait training (RAGT)
      compared to conventional overground training. METHODS: Sixty patients with motor
      incomplete spinal cord injury (SCI) were included in a prospective, randomized
      clinical trial by comparing RAGT to conventional overground training. The RAGT
      group received RAGT three sessions per week at duration of 40 minutes with
      regular physiotherapy in 4 weeks. The conventional group underwent regular
      physiotherapy twice a day, 5 times a week. Main outcomes were lower extremity
      motor score of American Spinal Injury Association impairment scale (LEMS),
      ambulatory motor index (AMI), Spinal Cord Independence Measure III mobility
      section (SCIM3-M), and walking index for spinal cord injury version II (WISCI-II)
      scale. RESULTS: At the end of rehabilitation, both groups showed significant
      improvement in LEMS, AMI, SCIM3-M, and WISCI-II. Based on WISCI-II, statistically
      significant improvement was observed in the RAGT group. For the remaining
      variables, no difference was found. CONCLUSION: RAGT combined with conventional
      physiotherapy could yield more improvement in ambulatory function than
      conventional therapy alone. RAGT should be considered as one additional tool to
      provide neuromuscular reeducation in patient with incomplete SCI.

PMID- 25566470
TI  - Effect of virtual reality on cognitive dysfunction in patients with brain tumor.
AB  - OBJECTIVE: To investigate whether virtual reality (VR) training will help the
      recovery of cognitive function in brain tumor patients. METHODS: Thirty-eight
      brain tumor patients (19 men and 19 women) with cognitive impairment recruited
      for this study were assigned to either VR group (n=19, IREX system) or control
      group (n=19). Both VR training (30 minutes a day for 3 times a week) and computer
      based cognitive rehabilitation program (30 minutes a day for 2 times) for 4 weeks
      were given to the VR group. The control group was given only the computer-based
      cognitive rehabilitation program (30 minutes a day for 5 days a week) for 4
      weeks. Computerized neuropsychological tests (CNTs), Korean version of Mini
      Mental Status Examination (K-MMSE), and Korean version of Modified Barthel Index
      (K-MBI) were used to evaluate cognitive function and functional status. RESULTS:
      The VR group showed improvements in the K-MMSE, visual and auditory continuous
      performance tests (CPTs), forward and backward digit span tests (DSTs), forward
      and backward visual span test (VSTs), visual and verbal learning tests, Trail
      Making Test type A (TMT-A), and K-MBI. The VR group showed significantly (p<0.05)
      better improvements than the control group in visual and auditory CPTs, backward
      DST and VST, and TMT-A after treatment. CONCLUSION: VR training can have
      beneficial effects on cognitive improvement when it is combined with computer
      assisted cognitive rehabilitation. Further randomized controlled studies with
      large samples according to brain tumor type and location are needed to
      investigate how VR training improves cognitive impairment.

PMID- 25566471
TI  - Clinical characteristics associated with aspiration or penetration in children
      with swallowing problem.
AB  - OBJECTIVE: To evaluate demographic characteristics of children with suspected
      dysphagia who underwent videofluoroscopic swallowing study (VFSS) and to identify
      factors related to penetration or aspiration. METHODS: Medical records of 352
      children (197 boys, 155 girls) with suspected dysphagia who were referred for
      VFSS were reviewed retrospectively. Clinical characteristics and VFSS findings
      were analyzed using univariate and multivariate analyses. RESULTS: Almost half of
      the subjects (n=175, 49%) were under 24 months of age with 62 subjects (18%) born
      prematurely. The most common condition associated with suspected dysphagia was
      central nervous system (CNS) disease. Seizure was the most common CNS disorder in
      children of 6 months old or younger. Brain tumor was the most important one for
      school-age children. Aspiration symptoms or signs were the major cause of
      referral for VFSS in children except for infants of 6 months old or where half of
      the subjects showed poor oral intake. Penetration or aspiration was observed in
      206 of 352 children (59%). Subjects under two years of age who were born
      prematurely at less than 34 weeks of gestation were significantly (p=0.026) more
      likely to show penetration or aspiration. Subjects with congenital disorder with
      swallow-related anatomical abnormalities had a higher percentage of penetration
      or aspiration with marginal statistical significance (p=0.074). Multivariate
      logistic regression analysis revealed that age under 24 months and an unclear
      etiology for dysphagia were factors associated with penetration or aspiration.
      CONCLUSION: Subjects with dysphagia in age group under 24 months with preterm
      history and unclear etiology for dysphagia may require VFSS. The most common
      condition associated with dysphagia in children was CNS disease.

PMID- 25566472
TI  - Korean version of the scale for the assessment and rating of ataxia in ataxic
      stroke patients.
AB  - OBJECTIVE: To investigate the intra-rater and inter-rater reliability and
      usefulness of the Korean version of the Scale for the Assessment and Rating of
      Ataxia (K-SARA) in ataxic stroke patients. METHODS: The original SARA was
      translated into Korean, back translated to English, and compared to the original
      version. Stroke patients (n=60) with ataxia were evaluated using the K-SARA by
      one physiatrist and one occupational therapist. All subjects were rated twice. We
      divided the subjects into 5 groups by Functional Ambulation Category (FAC) and 3
      groups based on the ataxia subscale of the National Institutes of Health Stroke
      Scale (NIHSS). The mean K-SARA scores representing each group of FAC and the
      ataxia subscale of NIHSS were compared. RESULTS: The test-retest correlation
      coefficient of the K-SARA was 0.997 by the therapist and 1.00 by the physiatrist
      (p<0.001). The inter-rater correlation coefficient of the K-SARA was 0.985
      (p<0.001). The ataxia subscale of NIHSS did not correlate with K-SARA. There was
      a significant difference in the mean K-SARA score by FAC (p<0.001). CONCLUSION: K
      SARA is a reliable and valid measure of ataxia in stroke patients in Korea.

PMID- 25566473
TI  - The differences in clinical aspect between specific language impairment and
      global developmental delay.
AB  - OBJECTIVE: To compare and analyze the clinical characteristics of children with
      delayed language acquisition due to two different diagnoses, which were specific
      language impairment (SLI, a primarily delayed language development) and global
      developmental delay (GDD, a language delay related to cognitive impairment).
      METHODS: Among 1,598 children who had visited the developmental delay clinic from
      March 2005 to February 2011, 467 children who were diagnosed with GDD and 183
      children who were diagnosed with SLI were included in this study. All children
      were questioned about past, family, and developmental history, and their language
      competences and cognitive function were assessed. Some children got
      electroencephalography (EEG), in case of need. RESULTS: The presence of the
      perinatal risk factors showed no difference in two groups. In the children with
      GDD, they had more delayed acquisition of independent walking and more frequent
      EEG abnormalities compared with the children with SLI (p<0.01). The positive
      family history of delayed language development was more prevalent in children
      with SLI (p<0.01). In areas of language ability, the quotient of receptive
      language and expressive language did not show any meaningful statistical
      differences between the two groups. Analyzing in each group, the receptive
      language quotient was higher than expressive language quotient in both group
      (p<0.01). In the GDD group, the Bayley Scales of Infant Development II (BSID-II)
      showed a marked low mental and motor quotient while the Wechsler Intelligence
      Scale showed low verbal and nonverbal IQ. In the SLI group, the BSID-II and
      Wechsler Intelligence Scale showed low scores in mental area and verbal IQ but
      sparing motor area and nonverbal IQ. CONCLUSION: The linguistic profiles of
      children with language delay could not differentiate between SLI and GDD. The
      clinicians needed to be aware of these developmental issues, and history taking
      and clinical evaluation, including cognitive assessment, could be helpful to
      diagnose adequately and set the treatment plan for each child.

PMID- 25566474
TI  - Characteristics of Cognitive Impairment in Patients With Post-stroke Aphasia.
AB  - OBJECTIVE: To analyze cognitive functions of post-stroke aphasia patients
      compared to patients having right hemispheric stroke and left hemispheric lesions
      without aphasia, and to look for a relationship between cognitive deficits and
      aphasia severity. METHODS: Thirty-six patients with right hemispheric stroke
      (group 1), 32 with left hemispheric lesion without aphasia (group 2), and 26 left
      hemispheric stroke patients with aphasia (group 3) completed a set of tests in
      the computerized neurocognitive function batteries for attention, executive
      function and intelligence and Korean version of Western Aphasia Battery. Data
      analyses explored cognitive characteristics among the three groups and the
      correlation between cognitive deficits and aphasia severity. RESULTS: Right
      hemispheric and left hemispheric stroke patients without aphasia showed similar
      findings except for digit span forward test. Cognitive tests for working memory
      and sustained attention were significantly impaired in the aphasic patients, but
      intelligence was shown to be similar in the three groups. Significant correlation
      between cognitive deficit and aphasia severity was only shown in some attention
      tests. CONCLUSION: Cognitive deficits may be accompanied with post-stroke aphasia
      and there are possible associations between language and cognitive measures.
      Therefore, detection and treatment towards coexisting cognitive impairment may be
      necessary for efficient aphasia treatment.

PMID- 25566475
TI  - Effects of atrial fibrillation on the outcome of the rehabilitation in patients
      with cerebral infarction.
AB  - OBJECTIVE: To evaluate the influence of atrial fibrillation (Af) on the clinical
      characteristics and rehabilitation outcomes of patients with cerebral infarction.
      METHODS: We evaluated 87 of 101 consecutive patients with cerebral infarction
      admitted to the department of physical medicine and rehabilitation during their
      rehabilitation period. The patients were divided into two groups, Af and non-Af
      groups. We estimated characteristics of patient demographic features, disease
      duration, length of hospital stay, other comorbidities and risk factors for
      stroke, and functional status at admission and at discharge and compared those in
      patients with and without Af. Functional Independence Measure (FIM), the Modified
      Barthel Index (MBI), and the PULSES profile (PULSES) were used to evaluate
      functional status. RESULTS: The number in the Af group was 20 (22.9%) and that of
      the non-Af group was 67 (77.1%). Demographic features, other comorbidities, motor
      function, cognitive function, neurological scales, and brain lesions did not
      differ significantly between the groups. The incidence of coronary artery disease
      and valvular heart disease were significantly correlated with the incidence of Af
      in multivariate analysis. Based on FIM, MBI, and PULSES scores, functional
      improvement in the Af group after rehabilitation was significantly less than that
      of the non-Af group. CONCLUSION: Af was shown to be associated with a markedly
      negative result in rehabilitation in patients with cerebral infarction. Thus,
      early recognition and proper treatment of Af may help patients achieve more
      effective rehabilitation.

PMID- 25566476
TI  - Usual dose of caffeine has a positive effect on somatosensory related postural
      stability in hemiparetic stroke patients.
AB  - OBJECTIVE: To evaluate the effect of caffeine on balance control of hemiparetic
      stroke patients, we investigated the difference in postural stability before and
      after drinking coffee by observing changes in stability index (SI) from
      posturography. METHODS: Thirty patients with history of stroke and 15 age-matched
      healthy subjects participated in this study. Effect of group factor (of the
      control and stroke groups) and treatment factor (pre- and post-drinking of
      coffee) on SI were tested in three conditions: with eyes opened, with eyes
      closed, and with a pillow support. The effects of these factors on visual
      deprivation and somatosensory change of subjects were also tested. RESULTS: Under
      all conditions, SI was higher in the stroke group than in the control group.
      Under eyes-open condition, the treatment factor was not statistically
      significant. Under eyes-closed condition, the interaction between group and
      treatment factor was statistically significant. After the subjects drank coffee,
      SI in the control group was increased. However, SI in the stroke group was
      decreased. Under pillow-supported condition, the interaction between group and
      treatment factor appeared marginally significant. For visual deprivation effect,
      the interaction between treatment and group factor was statistically significant.
      After caffeine consumption, the visual deprivation effect was increased in
      control group but decreased in the stroke group. For somatosensory change effect,
      the interaction between group and treatment factor was not statistically
      significant. CONCLUSION: Postural stability of hemiparetic stroke patients
      related to somatosensory information was improved after intake of usual dose of
      caffeine.

PMID- 25566477
TI  - Age specificity in general and rehabilitation medical services in children with
      cerebral palsy.
AB  - OBJECTIVE: To review the medical utilization in children with cerebral palsy
      according to age and discern particularities. METHODS: From January 2007 to
      December 2007, 10,659 children and adolescents between 1 and 18 years of age who
      had filed national insurance claims for a diagnosis of cerebral palsy were
      selected. Age was chosen as an independent variable, and the population was
      categorized into specific age groups to verify any differences in medical service
      utilization. Admission duration to rehabilitation, number of visits to
      rehabilitation outpatient clinics, numbers of admission dates and outpatient
      clinic visits for general medical services, number of rehabilitation
      utilizations, and type of rehabilitations treatment were selected as dependent
      variables. One-way ANOVA was used for statistical evaluation, and analysis was
      done with SAS software. RESULTS: In general medical use, adolescences diagnosed
      with cerebral palsy had the highest mean admission duration (p<0.001). The mean
      visit day to outpatient clinics for general medical services was highest for
      infants (p<0.001). In rehabilitation treatment, infants diagnosed with cerebral
      palsy had the highest mean admission duration (p<0.001). The mean visit day to
      outpatient clinics for rehabilitation treatment was highest for infants
      (p<0.001). CONCLUSION: Significant differences in use of general and
      rehabilitation medical services among pediatric age groups with cerebral palsy
      were evident. This implies that particular attention is necessary when setting up
      a national medical care policy for patient with cerebral palsy.

PMID- 25566478
TI  - Use of magnetic resonance imaging to identify outcome predictors of caudal
      epidural steroid injections for lower lumbar radicular pain caused by a herniated
      disc.
AB  - OBJECTIVE: We used lumbar magnetic resonance image (MRI) findings to determine
      possible outcome predictors of a caudal epidural steroid injection (CESI) for
      radicular pain caused by a herniated lumbar disc (HLD). METHODS: Ninety-one
      patients with radicular pain whose MRI indicated a HLD were enrolled between
      September 2010 and July 2013. The CESIs were performed using ultrasound (US). A
      responder was defined as having complete relief or at least a 50% reduction of
      pain as assessed by the visual analog scale (VAS) and functional status on the
      Roland Morris Disability Questionnaire (RMDQ); responder (VAS n=61, RMDQ n=51),
      and non-responder (VAS n=30, RMDQ n=40). MRI findings were analyzed and compared
      between the two groups with regard to HLD level, HLD type (protrusion or
      exclusion), HLD zone (central, subarticular, foraminal, and extraforaminal), HLD
      volume (mild, moderate, or severe), relationship between HLD and nerve root (no
      contact, contact, displaced, or compressed), disc height loss (none, less than
      half, or more than half ), and disc degeneration grade (homogeneous disc
      structure or inhomogeneous disc structure-clear nucleus and height of
      intervertebral disc). RESULTS: A centrally located herniated disc was more common
      in the responder group than that in the non-responder group. Treatment of
      centrally located herniated discs showed satisfactory results. (VAS p=0.025, RMDQ
      p=0.040). Other factors, such as HLD level, HLD type, HLD volume, relationship to
      nerve root, disc height loss, and disc degeneration grade, were not critical.
      CONCLUSION: The HLD zone was significant for pain reduction after CESI. A
      centrally located herniated disc was a predictor of a good clinical outcome.

PMID- 25566479
TI  - Cardiac rehabilitation after acute myocardial infarction resuscitated from
      cardiac arrest.
AB  - OBJECTIVE: To examine the safety and effectiveness of cardiac rehabilitation on
      patients resuscitated from cardiac arrest due to acute myocardial infarction.
      METHODS: The study included 23 subjects, including 8 with history of cardiac
      arrest and 15 without history of cardiac arrest. Both groups underwent initial
      graded exercise test (GXT) and subsequent cardiac rehabilitation for 6 weeks.
      After 6 weeks, both groups received follow-up GXT. RESULTS: Statistically
      significant (p<0.05) increase of VO2peak and maximal MVO2 but significant
      (p<0.05) decrease of submaximal MVO2 and resting heart rate were observed in both
      groups after 6 weeks of cardiac rehabilitation. An increasing trend of maximal
      heart rates was observed in both groups. However, the increase was not
      statistically significant (p>0.05). There was no statistically significant change
      of resting heart rate, maximal heart rate, maximal MVO2, or submaximal MVO2 in
      both groups after cardiac rehabilitation. Fatal cardiac complications, such as
      abnormal ECG, cardiac arrest, death or myocardial infarction, were not observed.
      All subjects finished the cardiac rehabilitation program. CONCLUSION: Improvement
      was observed in the exercise capacity of patients after aerobic exercise
      throughout the cardiac rehabilitation program. Therefore, cardiac rehabilitation
      can be safely administered for high-risk patients with history of cardiac arrest.
      Similar improvement in exercise capacity can be expected in patients without
      cardiac arrest experience.

PMID- 25566480
TI  - Effects of repeated steroid injection at subacromial bursa with different
      interval.
AB  - OBJECTIVE: To evaluate the effects of repeated steroid injection at subacromial
      bursa with different interval for patient with periarticular shoulder disorder.
      METHODS: Group A (n=10) received subacromial bursa injection only on their first
      visit, group C (n=10) received the injection on their first visit and one week
      later, and group B (n=10) received the injection on their first visit and two
      weeks later. All injections were done with a combination of 40 mg (1.0 mL) of
      triamcinolone and 5.0 mL 0.5% lidocaine (6 mL total). We examined the active
      range of motion (AROM) of the shoulder joint, visual analogue scale (VAS), and
      shoulder disability questionnaire (SDQ) at baseline at 1, 2, and 4 weeks after
      the initial injection. RESULTS: In VAS, comparing the changes in VAS between
      groups, group B showed significant improvements compared with group A or C at 4
      weeks after the initial injection (p<0.05). In SDQ, comparing the changes in SDQ
      between the groups, group B and C showed more improvement than group A at 4 weeks
      after the initial injection, but these results were not statistically significant
      (p>0.05). In AROM, comparing the changes in AROM of external rotation between
      groups, group B and C showed significant improvement compared with group A at 4
      weeks after the initial injection (p<0.05). CONCLUSION: It may be more effective
      in pain relief for patients with periarticular disorder to receive subacromial
      bursa injections twice with 2-week interval, as opposed to once.

PMID- 25566481
TI  - Usefulness of the computed tomography venography for evaluation of leg edema
      including deep vein thrombosis in rehabilitation patients.
AB  - OBJECTIVE: To investigate the usefulness of computed tomography venography (CTV)
      for evaluation of leg swelling, especially deep vein thrombosis (DVT), in
      rehabilitation patients. METHODS: A hundred twenty-three patients, who had
      performed CTV performed because of suspected DVT in our clinic, were enrolled. We
      performed chart reviews retrospectively and categorized CTV findings as follows:
      DVT distal to inguinal ligament and no compression lesion; DVT proximal to
      inguinal ligament and no compression lesion; DVT distal to inguinal ligament and
      anatomical variant (for example, May-Thurner syndrome); DVT due to compression of
      mass (cancer or cyst); DVT and other incidental abnormal finding; and no DVT and
      other possible causes of leg swelling. RESULTS: DVTs were found in 65 (53%)
      patients. DVTs were found at distal level (thigh or lower leg) to inguinal
      ligament in 47 patients. DVTs were found at proximal to inguinal ligament,
      usually undetectable with duplex ultrasonography, in 6 patients. DVTs caused by
      external compression, such as femoral vein and cancer mass, were found in 12
      patients (10%), which are also not easily detected with duplex ultrasonography.
      Other various causes of leg edema without DVT were found in 22 (18%) patients.
      CONCLUSION: CTV can evaluate more extensively venous problems in the pelvis and
      abdomen and detect other possible causes of leg swelling. Therefore, CTV can be a
      useful tool not only for easy detection of DVT but also for evaluating
      differential diagnosis of leg edema in rehabilitation patients.

PMID- 25566482
TI  - Radiologic assessment of forward head posture and its relation to myofascial pain
      syndrome.
AB  - OBJECTIVE: To assess head posture using cervical spine X-rays to find out whether
      forward head posture is related to myofascial pain syndrome (MPS) in neck and
      shoulder. METHODS: Eighty-eight participants who were diagnosed with MPS in neck
      and shoulder were evaluated in this study. Four parameters (distance among head,
      cervical spines, and shoulder, and cervical angle) were measured from lateral
      view of cervical spine X-ray. The location and number of trigger points in the
      neck and shoulder and symptom duration were evaluated for each patient. RESULTS:
      Both horizontal distances between C1 vertebral body and C7 spinous process and
      between the earhole and C7 vertebral body were negatively correlated with
      cervical angle reflecting cervical lordosis (p<0.05). Younger patients had
      significantly (p<0.05) less cervical angle with more forward head posture. There
      was no relationship between MPS (presence, location, and number of trigger
      points) and radiologic assessments (distance parameters and the cervical angle).
      CONCLUSION: Forward head posture and reduced cervical lordosis were seen more in
      younger patients with spontaneous neck pain. However, these abnormalities did not
      correlate with the location or the number of MPS. Further studies are needed to
      delineate the mechanism of neck pain in patients with forward head posture.

PMID- 25566484
TI  - Determination of an ideal stimulation site of the medial antebrachial cutaneous
      nerve using ultrasound and investigation of the efficiency.
AB  - OBJECTIVE: To determine an ideal stimulation site of the medial antebrachial
      cutaneous nerve (MACN) using ultrasound measurement and to compare the efficiency
      of the new stimulation site with the conventional stimulation site on the nerve
      conduction study. METHODS: Both arms of 15 healthy participants were measured
      using ultrasound. The MACN was identified in the transverse view at each 0, 2, 4,
      6, and 8 cm proximal sites from the medial epicondyle, and the distances to the
      median nerve and to the skin from the MACN were measured. The ideal stimulation
      site should be located at the level which can give the shortest distance from the
      skin and the longest distance from the median nerve in terms of volume
      conduction. To confirm the efficiency of the ideal site, we measured the
      amplitude of the MACN conduction study at the ideal site against one at the 4 cm
      proximal to the medial epicondyle (conventional site). RESULTS: The ultrasound
      showed the ideal stimulation site for the MACN could be the elbow crease line.
      However, the nerve conduction study revealed that the amplitudes of the MACN were
      significantly larger at the 4 cm proximal to the medial epicondyle compared with
      ones at the ideal site. CONCLUSION: The ideal stimulation site based on the
      ultrasound did not permit better stimulation site for the nerve conduction study
      of the MACN compared with the conventional site. Careful adjustment of the
      stimulation site on the basis of this study would contribute to an accurate
      conduction study of the MACN.

PMID- 25566483
TI  - Prognostic Factors Predicting Early Recovery of Pre-fracture Functional Mobility
      in Elderly Patients With Hip Fracture.
AB  - OBJECTIVE: To investigate the prognostic factors predicting the recovery of pre
      fracture functional mobility, we evaluated this by the use of ambulatory
      assistive devices in short-term follow-up. METHODS: Five hundred and fifty-three
      elderly patients who had undergone hip fracture operations from January 2006 to
      June 2013 were enrolled in this retrospective study. Clinical characteristics and
      predicted factors affecting functional recovery, such as the delay of
      rehabilitation after the operation, were reviewed. The functional status of the
      gait was classified as either a bedridden state, wheelchair-bound state, walker
      gait, single cane gait, and self-gait without any ambulatory assistance device.
      When this functional grade in patients who recovered after the surgery was
      compared to before the surgery, this state was considered 'functional recovery'.
      RESULTS: One hundred and ninety-two patients (34.7%) showed recovery of
      preoperative mobility in the first month after their operation. Multiple logistic
      regression analysis identified that the following four factors were significantly
      associated with a deterioration of functional recovery: old age (odds ratio [OR],
      0.95; 95% confidence interval [CI], 0.92-0.97), delays in rehabilitation after
      operation (OR, 0.94; 95% CI, 0.89-0.98), the presence of cognitive dysfunction
      (OR, 0.36; 95% CI, 0.18-0.71), and trochanteric fracturing (OR, 0.58; 95% CI,
      0.36-0.94). CONCLUSION: We found that old age, cognitive dysfunction,
      trochanteric fracture type, and delay of rehabilitation were associated with the
      deterioration of functional recovery after a hip fracture operation in the short
      term. Therefore, early rehabilitation was required to acquire functional recovery
      after a hip fracture operation in the short-term.

PMID- 25566485
TI  - Ruptured popliteal cyst diagnosed by ultrasound before evaluation for deep vein
      thrombosis.
AB  - Most popliteal cysts are asymptomatic. However, cysts may rupture, resulting in
      pain and swelling of the leg that could also arise from other diseases, including
      deep vein thrombosis, lymphedema, cellulitis, and tear of a muscle or tendon.
      Therefore, it is difficult to diagnose a ruptured popliteal cyst based on only a
      patient's history and physical examination. Musculoskeletal ultrasound has been
      regarded as a diagnostic tool for ruptured popliteal cyst. Here, we describe a
      patient who was rapidly diagnosed as ruptured popliteal cyst by ultrasonography.
      Therefore, ultrasound could be used to distinguish a ruptured popliteal cyst from
      other diseases in patients with painful swollen legs before evaluation for deep
      vein thrombosis. 

PMID- 25566486
TI  - Apraxia of eyelid opening after brain injury: a case report.
AB  - Apraxia of eyelid opening (AEO) is a syndrome characterized by the patient's
      difficulty in initiating eyelid elevation spontaneously. Most of the reported
      cases were associated with extrapyramidal diseases. We report a case of AEO
      presented after traumatic brain injury, not with extrapyramidal diseases, and
      improved by dopaminergic treatment. A 49-year-old man underwent a traffic
      accident and was transferred to the emergency room in an unconscious state. Brain
      computed tomography (CT) revealed a subdural and epidural hemorrhage at right
      temporal and bilateral frontal lobes, and he received burr-hole trephination.
      After receiving comprehensive treatment including occupational therapy, cognition
      and mobility gradually improved, but he could not open his eyes voluntarily. With
      dopaminergic treatment (levodopa/benserazide 200/50 mg), he started to open his
      eyes spontaneously, especially when eating and undergoing physical training. This
      case showed that AEO may occur after brain injury and that dopaminergic treatment
      is beneficial also in AEO patients without extrapyramidal diseases. 

PMID- 25566487
TI  - Churg-strauss syndrome presented with hearing impairment and facial palsy.
AB  - Churg-Strauss syndrome (CSS) is a rare systemic necrotizing vasculitis. Cranial
      nerve involvement is very rare in CSS. A 59-year-old woman had complained of both
      hearing impairments for eight months and left facial palsy for three months. Left
      facial and cochlear neuropathies were detected in electrodiagnostic studies.
      Paranasal sinus computed tomography (CT) showed chronic pansinusitis. Chest CT
      revealed eosinophilic infiltration in the right upper lobe. Tissue biopsy of the
      right inferior turbinate displayed necrotizing vasculitis with eosinophilic
      infiltration. She was diagnosed as CSS, based on the presence of eosinophilia,
      pulmonary infiltration, paranasal sinusitis, and biopsy containing blood vessels
      with extravascular eosinophils. She was treated with intravenous and oral
      steroids and azathioprine, showing relatively good prognosis on facial palsy and
      hearing impairment. We report a very rare case of CSS presented with hearing
      impairment and facial palsy. 

PMID- 25566488
TI  - Paraplegia in a Patient With IgG4-Related Sclerosing Disease: A Case Report.
AB  - Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease,
      characterized by mass forming inflammatory lesions which respond well to steroid
      therapy. Pancreas is the most common site of involvement, and other organ
      involvements are also common. However, there are only a few reports about central
      nervous system involvement. We report a case of IgG4-related sclerosing disease
      which involves spinal cord causing paraplegia. A middle-aged female presented
      with sudden lower limb weakness. Magnetic resonance imaging showed a soft tissue
      mass which was diffusely compressing spinal cord along the C7 to T5 levels.
      Intravenous steroid pulse therapy and emergent operation was performed. The
      immunopathologic findings revealed IgG4-related sclerosing pachymeningitis
      postoperatively. There was no evidence of other organ involvement. Her neurologic
      deficit remained unchanged after two months of comprehensive rehabilitation
      therapy. 

PMID- 25566489
TI  - Chest wall pain as the presenting symptom of leptomeningeal carcinomatosis.
AB  - Leptomeningeal metastasis (LMM), also referred to as leptomeningeal
      carcinomatosis, results from diffuse infiltration of the leptomeninges by
      malignant cells originating from extra-meningeal primary tumors. It occurs in
      approximately 5%-10% of patients with solid tumor. Among solid tumors, the most
      common types leading to infiltration of the leptomeninges are breast cancer, lung
      cancer, and melanoma. Patients with LMM may present various signs and symptoms.
      Herein, we report a rare case with initial presentation of isolated chest wall
      pain. Computed tomography of the chest with contrast revealed a 2.5-cm nodule
      over the left upper lung. Biopsy confirmed the diagnosis of adenocarcinoma.
      Later, cerebrospinal fluid cytology exam also confirmed leptomeningeal seeding.
      It is rare for leptomeningeal carcinomatosis patients to present with chest wall
      pain. Therefore, a high index of suspicion is mandatory for accurate and prompt
      diagnosis. 

PMID- 25566490
TI  - Kinematic changes in swallowing after surgical removal of anterior cervical
      osteophyte causing Dysphagia: a case series.
AB  - This retrospective case series included five patients who underwent surgical
      resection of the cervical anterior osteophyte due to dysphagia. Videofluoroscopic
      swallowing studies (VFSSs) were performed before and after surgery on each
      patient, and kinematic analysis of the video clips from the VFSS of a 5-mL liquid
      barium swallow was carried out. Functional oral intake improved after surgery in
      3/4 patients who had required a modified diet before surgery. Kinematic analysis
      showed increases in the maximal hyoid vertical movement length (13.16+/-5.87 to
      19.09+/-4.77 mm, p=0.080), hyoid movement velocities (170.24+/-84.71 to 285.53+/
      104.55 mm/s, p=0.043), and upper esophageal sphincter opening width (3.97+/-0.42
      to 6.39+/-1.32 mm, p=0.043) after surgery. In conclusion, improved upper
      esophageal sphincter opening via enhancement of hyoid movement after cervical
      anterior osteophyte resection may be the kinetic mechanism of improved swallowing
      function. 

PMID- 25566491
TI  - Intracranial Hemorrhage in the Corpus Callosum Presenting as Callosal
      Disconnection Syndrome: FDG-PET and Tractography: A Case Report.
AB  - We report the findings of (18)F-fluorodeoxyglocese positron emission tomography
      (FDG-PET) and diffusion tensor tractography (DTT) in a right-handed patient
      presenting with callosal disconnection syndrome, including alien hand syndrome,
      after an anterior communicating artery aneurysmal rupture. The 49-year-old
      patient had right hemiparesis and unintended movement of the right hand during
      action of the left hand. A brain magnetic resonance imaging revealed lesions in
      the upper part of the genu and body in the corpus callosum as well as hemorrhage
      in the inter-hemispheric fissure. We observed extensive disruption of corpus
      callosum fibers in the upper genu and trunk by DTT for the evaluation of inter
      hemispheric connection. FDG-PET revealed severe hypometabolism in the left
      cerebral hemisphere, including basal ganglia and thalamus, and hypermetabolism in
      the right cerebral hemisphere. Based on findings of FDG-PET and DTT, the callosal
      disconnection syndrome presented in the patient could be the result of loss of
      transcallosal inhibition in the contralateral hemisphere. 

PMID- 25566492
TI  - Regarding to the article 'effect of lumbar stabilization and dynamic lumbar
      strengthening exercises in patients with chronic low back pain'.

PMID- 25566493
TI  - A reply to the questions regarding to the article 'effect of lumbar stabilization
      and dynamic lumbar strengthening exercises in patients with chronic low back
      pain'.

PMID- 25566496
TI  - EMT or EMT-Promoting Transcription Factors, Where to Focus the Light?

PMID- 25566495
TI  - Exploiting synergy: immune-based combinations in the treatment of prostate
      cancer.
AB  - Cancer treatment is being revolutionized by the emergence of immunotherapies such
      as immune checkpoint inhibitors and therapeutic cancer vaccines. Prostate cancer
      is amenable to such therapeutic approaches. The improved understanding of the
      relationship between the immune system and tumors has allowed therapeutic
      targeting of immune checkpoints and tumor associated antigens to be developed.
      Furthermore, interventions used in prostate cancer are capable of impacting the
      immune system. As demonstrated by preclinical data and emerging clinical data,
      radiation therapy, anti-androgen therapy, and chemotherapy can be used with
      immunotherapies to obtain synergistic results. Current and future clinical trials
      will further investigate these principles as immunotherapeutics are combined with
      each other and standard therapies for optimal clinical utility. 

PMID- 25566494
TI  - The Basic Biology of PP2A in Hematologic Cells and Malignancies.
AB  - Reversible protein phosphorylation plays a crucial role in regulating cell
      signaling. In normal cells, phosphoregulation is tightly controlled by a network
      of protein kinases counterbalanced by several protein phosphatases. Deregulation
      of this delicate balance is widely recognized as a central mechanism by which
      cells escape external and internal self-limiting signals, eventually resulting in
      malignant transformation. A large fraction of hematologic malignancies is
      characterized by constitutive or unrestrained activation of oncogenic kinases.
      This is in part achieved by activating mutations, chromosomal rearrangements, or
      constitutive activation of upstream kinase regulators, in part by inactivation of
      their anti-oncogenic phosphatase counterparts. Protein phosphatase 2A (PP2A)
      represents a large family of cellular serine/threonine phosphatases with
      suspected tumor suppressive functions. In this review, we highlight our current
      knowledge about the complex structure and biology of these phosphatases in
      hematologic cells, thereby providing the rationale behind their diverse signaling
      functions. Eventually, this basic knowledge is a key to truly understand the
      tumor suppressive role of PP2A in leukemogenesis and to allow further rational
      development of therapeutic strategies targeting PP2A. 

PMID- 25566497
TI  - Pharmacological doses of daily ascorbate protect tumors from radiation damage
      after a single dose of radiation in an intracranial mouse glioma model.
AB  - Pharmacological ascorbate is currently used as an anti-cancer treatment,
      potentially in combination with radiation therapy, by integrative medicine
      practitioners. In the acidic, metal-rich tumor environment, ascorbate acts as a
      pro-oxidant, with a mode of action similar to that of ionizing radiation; both
      treatments kill cells predominantly by free radical-mediated DNA damage. The
      brain tumor, glioblastoma multiforme (GBM), is very resistant to radiation;
      radiosensitizing GBM cells will improve survival of GBM patients. Here, we
      demonstrate that a single fraction (6 Gy) of radiation combined with a 1 h
      exposure to ascorbate (5 mM) sensitized murine glioma GL261 cells to radiation in
      survival and colony-forming assays in vitro. In addition, we report the effect of
      a single fraction (4.5 Gy) of whole brain radiation combined with daily
      intraperitoneal injections of ascorbate (1 mg/kg) in an intracranial GL261 glioma
      mouse model. Tumor-bearing C57BL/6 mice were divided into four groups: one group
      received a single dose of 4.5 Gy to the brain 8 days after tumor implantation, a
      second group received daily intraperitoneal injections of ascorbate (day 8-45)
      after implantation, a third group received both treatments and a fourth control
      group received no treatment. While radiation delayed tumor progression,
      intraperitoneal ascorbate alone had no effect on tumor progression. Tumor
      progression was faster in tumor-bearing mice treated with radiation and daily
      ascorbate than in those treated with radiation alone. Histological analysis
      showed less necrosis in tumors treated with both radiation and ascorbate,
      consistent with a radio-protective effect of ascorbate in vivo. Discrepancies
      between our in vitro and in vivo results may be explained by differences in the
      tumor microenvironment, which determines whether ascorbate remains outside the
      cell, acting as a pro-oxidant, or whether it enters the cells and acts as an anti
      oxidant. 

PMID- 25566498
TI  - Crosstalk of Oncogenic Signaling Pathways during Epithelial-Mesenchymal
      Transition.
AB  - Epithelial-mesenchymal transition (EMT) and cell transformation have been well
      documented in multiple cancer cell models and are believed to be one of the
      earliest events in tumor progression. Genetic and epigenetic modifications shift
      cells toward either end of the EMT spectrum, and can be influenced by the
      microenvironment surrounding a tumor. EMT and mesenchymal-epithelial transition
      are critical to normal function and development and an intricate network of
      transcription factors and transcriptional regulators tightly regulates these
      processes. As evidenced in normal and transformed cell lines, many signaling
      pathways trigger EMT during development and differentiation. The signaling
      pathways include those triggered by different members of the transforming growth
      factor superfamily, epidermal growth factor, fibroblast growth factor, hepatocyte
      growth factor, hypoxia-inducible factor, Wnt, Notch, and many others. Functional
      redundancies allow cells to undergo EMT even if these key transcriptional
      regulators are lacking, but these same redundancies also make these pathways
      particularly susceptible to gain-of-function mutations or constitutive signal
      activation; the "forced" transition toward either a mesenchymal or epithelial
      phenotype. 

PMID- 25566500
TI  - The emerging role of exosomes in epithelial-mesenchymal-transition in cancer.
AB  - Metastasis in cancer consists of multiple steps, including epithelial-mesenchymal
      transition (EMT), which is characterized by the loss of epithelial-like
      characteristics and the gain of mesenchymal-like attributes including cell
      migration and invasion. It is clear that the tumor microenvironment can promote
      the metastatic cascade and that intercellular communication is necessary for this
      to occur. Exosomes are small membranous vesicles secreted by most cell types into
      the extracellular environment and they are important communicators in the tumor
      microenvironment. They promote angiogenesis, invasion, and proliferation in
      recipient cells to support tumor growth and a prometastatic phenotype. Although
      it is clear that exosomes contribute to cancer cell plasticity, experimental
      evidence to define exosome induced plasticity as EMT is only just coming to
      light. This review will discuss recent research on exosomal regulation of the EMT
      process in the tumor microenvironment. 

PMID- 25566499
TI  - Notch-EGFR/HER2 Bidirectional Crosstalk in Breast Cancer.
AB  - The Notch pathway is a well-established mediator of cell-cell communication that
      plays a critical role in stem cell survival, self-renewal, cell fate decisions,
      tumorigenesis, invasion, metastasis, and drug resistance in a variety of cancers.
      An interesting form of crosstalk exists between the Notch receptor and the
      Epidermal Growth Factor Receptor Tyrosine Kinase family, which consists of HER-1,
      -2, -3, and -4. Overexpression of HER and/or Notch occurs in several human
      cancers including brain, lung, breast, ovary, and skin making them potent
      oncogenes capable of advancing malignant disease. Continued assessment of
      interplay between these two critical signaling networks uncovers new insight into
      mechanisms used by HER-driven cancer cells to exploit Notch as a compensatory
      pathway. The compensatory Notch pathway maintains HER-induced downstream signals
      transmitted to pathways such as Mitogen Activated Protein Kinase and
      Phosphatidylinositol 3-Kinase (PI3K), thereby allowing cancer cells to survive
      molecular targeted therapies, undergo epithelial to mesenchymal transitioning,
      and increase cellular invasion. Uncovering the critical crosstalk between the HER
      and Notch pathways can lead to improved screening for the expression of these
      oncogenes enabling patients to optimize their personal treatment options and
      predict potential treatment resistance. This review will focus on the current
      state of crosstalk between the HER and Notch receptors and the effectiveness of
      current therapies targeting HER-driven cancers. 

PMID- 25566501
TI  - A role for naturally occurring alleles of endoplasmic reticulum aminopeptidases
      in tumor immunity and cancer pre-disposition.
AB  - Endoplasmic reticulum aminopeptidase 1 and 2 (ERAP1 and ERAP2) are key components
      on the pathway that generates antigenic epitopes for presentation to cytotoxic T
      lymphocytes (CTLs). Coding single nucleotide polymorphisms (SNPs) in these
      enzymes have been associated with pre-disposition to several major human diseases
      including inflammatory diseases with autoimmune etiology, viral infections, and
      virally induced cancer. The function of these enzymes has been demonstrated to
      affect CTL and natural killer cell responses toward healthy and malignant cells
      as well as the production of inflammatory cytokines. Recent studies have
      demonstrated that SNPs in ERAP1 and ERAP2 can affect their ability to generate or
      destroy antigenic epitopes and define the immunopeptidome. In this review, we
      examine the potential role of these enzymes and their polymorphic states on the
      generation of cytotoxic responses toward malignantly transformed cells. Given the
      current state-of-the-art, it is possible that polymorphic variation in these
      enzymes may contribute to the individual's pre-disposition to cancer through
      altered generation or destruction of tumor antigens that can facilitate tumor
      immune evasion. 

PMID- 25566503
TI  - Mitochondrial Proteins (e.g., VDAC, Bcl-2, HK, ANT) as Major Control Points in
      Oncology.

PMID- 25566505
TI  - Effects of epithelial to mesenchymal transition on T cell targeting of melanoma
      cells.
AB  - Melanoma cells can switch phenotype in a manner similar to epithelial to
      mesenchymal transition (EMT). In this perspective article, we address the effects
      of such phenotype switching on T cell targeting of tumor cells. During the EMT
      like switch in phenotype, a concomitant change in expression of multiple tumor
      antigens occurs. Melanoma cells undergoing EMT escape from killing by T cells
      specific for antigens whose expression is downregulated by this process. We
      discuss melanoma antigens whose expression is influenced by EMT. We assess the
      effect of changes in the expressed tumor antigen repertoire on T-cell mediated
      tumor recognition and killing. In addition to escape from T cell immunity via
      changes in antigen expression, mesenchymal-like melanoma cells are generally more
      resistant to classical chemotherapy and radiotherapy. However, we demonstrate
      that when targeting antigens whose expression is unaltered during EMT, the
      capacity of T cells to kill melanoma cell lines in vitro is not influenced by
      their phenotype. When considering immune therapies such as cancer vaccination,
      these data suggest escape from T cell killing due to phenotype switching in
      melanoma could potentially be avoided by careful selection of target antigen. 

PMID- 25566504
TI  - Emerging understanding of multiscale tumor heterogeneity.
AB  - Cancer is a multifaceted disease characterized by heterogeneous genetic
      alterations and cellular metabolism, at the organ, tissue, and cellular level.
      Key features of cancer heterogeneity are summarized by 10 acquired capabilities,
      which govern malignant transformation and progression of invasive tumors. The
      relative contribution of these hallmark features to the disease process varies
      between cancers. At the DNA and cellular level, germ-line and somatic gene
      mutations are found across all cancer types, causing abnormal protein production,
      cell behavior, and growth. The tumor microenvironment and its individual
      components (immune cells, fibroblasts, collagen, and blood vessels) can also
      facilitate or restrict tumor growth and metastasis. Oncology research is
      currently in the midst of a tremendous surge of comprehension of these disease
      mechanisms. This will lead not only to novel drug targets but also to new
      challenges in drug discovery. Integrated, multi-omic, multiplexed technologies
      are essential tools in the quest to understand all of the various cellular
      changes involved in tumorigenesis. This review examines features of cancer
      heterogeneity and discusses how multiplexed technologies can facilitate a more
      comprehensive understanding of these features. 

PMID- 25566506
TI  - Fanconi anemia repair pathway dysfunction, a potential therapeutic target in lung
      cancer.
AB  - The Fanconi anemia (FA) pathway is a major mechanism of homologous recombination
      DNA repair. The functional readout of the pathway is activation through mono
      ubiquitination of FANCD2 leading to nuclear foci of repair. We have recently
      developed an FA triple-staining immunofluorescence based method (FATSI) to
      evaluate FANCD2 foci formation in formalin fixed paraffin-embedded (FFPE) tumor
      samples. DNA-repair deficiencies have been considered of interest in lung cancer
      prevention, given the persistence of damage produced by cigarette smoke in this
      setting, as well as in treatment, given potential increased efficacy of DNA
      damaging drugs. We screened 139 non-small cell lung cancer (NSCLC) FFPE tumors
      for FANCD2 foci formation by FATSI analysis. Among 104 evaluable tumors, 23 (22%)
      were FANCD2 foci negative, thus repair deficient. To evaluate and compare novel
      targeted agents in the background of FA deficiency, we utilized RNAi technology
      to render several lung cancer cell lines FANCD2 deficient. Successful FANCD2
      knockdown was confirmed by reduction in the FANCD2 protein. Subsequently, we
      treated the FA defective H1299D2-down and A549D2-down NSCLC cells and their FA
      competent counterparts (empty vector controls) with the PARP inhibitors veliparib
      (ABT-888) (5 MUM) and BMN673 (0.5 MUM), as well as the CHK1 inhibitor Arry-575 at
      a dose of 0.5 MUM. We also treated the FA defective small cell lung cancer cell
      lines H719D2-down and H792D2-down and their controls with the BCL-2/XL inhibitor
      ABT-263 at a dose of 2 MUM. The treated cells were harvested at 24, 48, and 72 h
      post treatment. MTT cell viability analysis showed that each agent was more
      cytotoxic to the FANCD2 knock-down cells. In all tests, the FA defective lung
      cancer cells had less viable cells as comparing to controls 72 h post treatment.
      Both MTT and clonogenic analyses comparing the two PARP inhibitors, showed that
      BMN673 was more potent compared to veliparib. Given that FA pathway plays
      essential roles in response to DNA damage, our results suggest that a subset of
      lung cancer patients are likely to be more susceptible to DNA cross-link based
      therapy, or to treatments in which additional repair mechanisms are targeted.
      These subjects can be identified through FATSI analysis. Clinical trials to
      evaluate this therapeutic concept are needed. 

PMID- 25566502
TI  - The host microenvironment influences prostate cancer invasion, systemic spread,
      bone colonization, and osteoblastic metastasis.
AB  - Prostate cancer (PCa) is the second leading cause of cancer death in men
      worldwide. Most PCa deaths are due to osteoblastic bone metastases. What triggers
      PCa metastasis to the bone and what causes osteoblastic lesions remain
      unanswered. A major contributor to PCa metastasis is the host microenvironment.
      Here, we address how the primary tumor microenvironment influences PCa metastasis
      via integrins, extracellular proteases, and transient epithelia-mesenchymal
      transition (EMT) to promote PCa progression, invasion, and metastasis. We discuss
      how the bone-microenvironment influences metastasis; where chemotactic cytokines
      favor bone homing, adhesion molecules promote colonization, and bone-derived
      signals induce osteoblastic lesions. Animal models that fully recapitulate human
      PCa progression from primary tumor to bone metastasis are needed to understand
      the PCa pathophysiology that leads to bone metastasis. Better delineation of the
      specific processes involved in PCa bone metastasize is needed to prevent or treat
      metastatic PCa. Therapeutic regimens that focus on the tumor microenvironment
      could add to the PCa pharmacopeia. 

PMID- 25566507
TI  - Androgen-targeted therapy-induced epithelial mesenchymal plasticity and
      neuroendocrine transdifferentiation in prostate cancer: an opportunity for
      intervention.
AB  - Androgens regulate biological pathways to promote proliferation, differentiation,
      and survival of benign and malignant prostate tissue. Androgen receptor (AR)
      targeted therapies exploit this dependence and are used in advanced prostate
      cancer to control disease progression. Contemporary treatment regimens involve
      sequential use of inhibitors of androgen synthesis or AR function. Although
      targeting the androgen axis has clear therapeutic benefit, its effectiveness is
      temporary, as prostate tumor cells adapt to survive and grow. The removal of
      androgens (androgen deprivation) has been shown to activate both epithelial-to
      mesenchymal transition (EMT) and neuroendocrine transdifferentiation (NEtD)
      programs. EMT has established roles in promoting biological phenotypes associated
      with tumor progression (migration/invasion, tumor cell survival, cancer stem cell
      like properties, resistance to radiation and chemotherapy) in multiple human
      cancer types. NEtD in prostate cancer is associated with resistance to therapy,
      visceral metastasis, and aggressive disease. Thus, activation of these programs
      via inhibition of the androgen axis provides a mechanism by which tumor cells can
      adapt to promote disease recurrence and progression. Brachyury, Axl, MEK, and
      Aurora kinase A are molecular drivers of these programs, and inhibitors are
      currently in clinical trials to determine therapeutic applications. Understanding
      tumor cell plasticity will be important in further defining the rational use of
      androgen-targeted therapies clinically and provides an opportunity for
      intervention to prolong survival of men with metastatic prostate cancer. 

PMID- 25566508
TI  - Vibrio parahaemolyticus strengthens their virulence through modulation of
      cellular reactive oxygen species in vitro.
AB  - Vibrio parahaemolyticus (Vp) is one of the emergent food-borne pathogens that are
      commensally associated with various shellfish species throughout the world. It is
      strictly environmental and many strains are pathogenic to humans. The virulent
      strains cause distinct diseases, including wound infections, septicemia, and most
      commonly, acute gastroenteritis, which is acquired through the consumption of raw
      or undercooked seafood, especially shellfish. Vp has two type three secretion
      systems (T3SSs), which triggering its cytotoxicity and enterotoxicity via their
      effectors. To better understand the pathogenesis of Vp, we established a cell
      infection model in vitro using a non-phagocytic cell line. Caco-2 cells were
      infected with different strains of Vp (pandemic and non-pandemic strains) and
      several parameters of cytotoxicity were measured together with adhesion and
      invasion indices, which reflect the pathogen's virulence. Our results show that
      Vp adheres to cell monolayers and can invade non-phagocytic cells. It also
      survives and persists in non-phagocytic cells by modulating reactive oxygen
      species (ROS), allowing its replication, and resulting in complete cellular
      destruction. We conclude that the pathogenicity of Vp is based on its capacities
      for adhesion and invasion. Surprisingly's; enhanced of ROS resistance period
      could promote the survival of Vp inside the intestinal tract, facilitating tissue
      infection by repressing the host's oxidative stress response. 

PMID- 25566509
TI  - Modeling early events in Francisella tularensis pathogenesis.
AB  - Computational models can provide valuable insights into the mechanisms of
      infection and be used as investigative tools to support development of medical
      treatments. We develop a stochastic, within-host, computational model of the
      infection process in the BALB/c mouse, following inhalational exposure to
      Francisella tularensis SCHU S4. The model is mechanistic and governed by a small
      number of experimentally verifiable parameters. Given an initial dose, the model
      generates bacterial load profiles corresponding to those produced experimentally,
      with a doubling time of approximately 5 h during the first 48 h of infection.
      Analytical approximations for the mean number of bacteria in phagosomes and
      cytosols for the first 24 h post-infection are derived and used to verify the
      stochastic model. In our description of the dynamics of macrophage infection, the
      number of bacteria released per rupturing macrophage is a geometrically
      distributed random variable. When combined with doubling time, this provides a
      distribution for the time taken for infected macrophages to rupture and release
      their intracellular bacteria. The mean and variance of these distributions are
      determined by model parameters with a precise biological interpretation,
      providing new mechanistic insights into the determinants of immune and bacterial
      kinetics. Insights into the dynamics of macrophage suppression and activation
      gained by the model can be used to explore the potential benefits of
      interventions that stimulate macrophage activation. 

PMID- 25566510
TI  - Granulomatous response to Coxiella burnetii, the agent of Q fever: the lessons
      from gene expression analysis.
AB  - The formation of granulomas is associated with the resolution of Q fever, a
      zoonosis due to Coxiella burnetii; however the molecular mechanisms of granuloma
      formation remain poorly understood. We generated human granulomas with peripheral
      blood mononuclear cells (PBMCs) and beads coated with C. burnetii, using BCG
      extracts as controls. A microarray analysis showed dramatic changes in gene
      expression in granuloma cells of which more than 50% were commonly modulated
      genes in response to C. burnetii and BCG. They included M1-related genes and
      genes related to chemotaxis. The inhibition of the chemokines, CCL2 and CCL5,
      directly interfered with granuloma formation. C. burnetii granulomas also
      expressed a specific transcriptional profile that was essentially enriched in
      genes associated with type I interferon response. Our results showed that
      granuloma formation is associated with a core of transcriptional response based
      on inflammatory genes. The specific granulomatous response to C. burnetii is
      characterized by the activation of type 1 interferon pathway. 

PMID- 25566511
TI  - Glycolipids from seaweeds and their potential biotechnological applications.
AB  - Marine macroalgae, or seaweeds, are a formidable source of natural compounds with
      diverse biological activities. In the last five decades it has been estimated
      that more than 3000 natural compounds were discovered from these organisms. The
      great majority of the published works have focused on terpenoids. In comparison,
      glycolipids are a neglected class of macroalgal secondary metabolites therefore
      remaining as a largely unknown reservoir of molecular diversity. Nevertheless,
      the interest regarding these compounds has been growing fast in the last decades
      as activities of ecological or pharmaceutical interest have been highlighted.
      This paper will review recent work regarding isolation and structural
      characterization of glycolipids from seaweeds and their prospective biological
      activities. 

PMID- 25566512
TI  - Mechanisms of Borrelia burgdorferi internalization and intracellular innate
      immune signaling.
AB  - Lyme disease is a long-term infection whose most severe pathology is
      characterized by inflammatory arthritis of the lower bearing joints, carditis,
      and neuropathy. The inflammatory cascades are initiated through the early
      recognition of invading Borrelia burgdorferi spirochetes by cells of the innate
      immune response, such as neutrophils and macrophage. B. burgdorferi does not have
      an intracellular niche and thus much research has focused on immune pathways
      activated by pathogen recognition molecules at the cell surface, such as the Toll
      like receptors (TLRs). However, in recent years, studies have shown that
      internalization of the bacterium by host cells is an important component of the
      defense machinery in response to B. burgdorferi. Upon internalization, B.
      burgdorferi is trafficked through an endo/lysosomal pathway resulting in the
      activation of a number of intracellular pathogen recognition receptors including
      TLRs and Nod-like receptors (NLRs). Here we will review the innate immune
      molecules that participate in both cell surface and intracellular immune
      activation by B. burgdorferi. 

PMID- 25566513
TI  - Staphylococcus aureus biofilms: recent developments in biofilm dispersal.
AB  - Staphylococcus aureus is a major cause of nosocomial and community-acquired
      infections and represents a significant burden on the healthcare system. S.
      aureus attachment to medical implants and host tissue, and the establishment of a
      mature biofilm, play an important role in the persistence of chronic infections.
      The formation of a biofilm, and encasement of cells in a polymer-based matrix,
      decreases the susceptibility to antimicrobials and immune defenses, making these
      infections difficult to eradicate. During infection, dispersal of cells from the
      biofilm can result in spread to secondary sites and worsening of the infection.
      In this review, we discuss the current understanding of the pathways behind
      biofilm dispersal in S. aureus, with a focus on enzymatic and newly described
      broad-spectrum dispersal mechanisms. Additionally, we explore potential
      applications of dispersal in the treatment of biofilm-mediated infections. 

PMID- 25566514
TI  - Myeloid decidual dendritic cells and immunoregulation of pregnancy: defective
      responsiveness to Coxiella burnetii and Brucella abortus.
AB  - Dendritic cells (DCs) are a component of the placental immune system, but their
      role in pregnancy is still poorly understood. Decidual DCs (dDCs) were selected
      from at-term pregnancy on the basis of CD14 and CD11c expression. A phenotypic
      analysis revealed that dDCs are characterized by the expression of monocyte
      derived DC (moDCs) markers and specific markers such as HLA-G and its ligand
      ILT4. As demonstrated by whole-genome microarray, dDCs expressed a specific gene
      program markedly distinct from that of moDCs; it included estrogen- and
      progesterone-regulated genes and genes encoding immunoregulatory cytokines, which
      is consistent with the context of foeto-maternal tolerance. A functional analysis
      of dDCs showed that they were unable to mature in response to bacterial ligands
      such as lipopolysaccharide or peptidoglycan, as assessed by the expression of HLA
      DR, CD80, CD83, and CD86. When dDCs were incubated with bacteria known for their
      placenta tropism, Coxiella burnetii and Brucella abortus, they were also unable
      to mature and to produce inflammatory cytokines. It is likely that the defective
      maturation of dDCs and their inability to produce inflammatory cytokines is
      related to the spontaneous release of IL-10 by these cells. Taken together, these
      results suggest that dDCs exhibit an immunoregulatory program, which may favor
      the pathogenicity of C. burnetii or B. abortus. 

PMID- 25566515
TI  - The complexity of Rab5 to Rab7 transition guarantees specificity of pathogen
      subversion mechanisms.

PMID- 25566516
TI  - Severe Neonatal Epileptic Encephalopathy and KCNQ2 Mutation: Neuropathological
      Substrate?
AB  - BACKGROUND: Neonatal convulsions are clinical manifestations in a heterogeneous
      group of disorders with different etiology and outcome. They are attributed to
      several genetic causes. METHODS: We describe a patient with intractable neonatal
      seizures who died from respiratory compromise during a status epilepticus.
      RESULTS: This case report provides electroencephalogram (EEG), MRI, genetic
      analysis, and neuropathological data. Genetic analysis revealed a de novo
      heterozygous missense mutation in the KCNQ2 gene, which encodes a subunit of a
      voltage-gated potassium channel. KCNQ2 gene mutation is associated with
      intractable neonatal seizures. EEG, MRI, data as well as mutation analysis have
      been described in other KCNQ2 cases. Post-mortem neuropathological investigation
      revealed mild malformation of cortical development with increased heterotopic
      neurons in the deep white matter compared to an age-matched control subject. The
      new finding of this study is the combination of a KCNQ2 mutation and the cortical
      abnormalities. CONCLUSION: KCNQ2 mutations should be considered in neonates with
      refractory epilepsy of unknown cause. The mild cortical malformation is an
      important new finding, though it remains unknown whether these cortical
      abnormalities are due to the KCNQ2 mutation or are secondary to the refractory
      seizures.

PMID- 25566517
TI  - Evaluation of the factor structure of the obstacles to engagement scale with low
      income african american parents.
AB  - OBJECTIVE: Parenting anticipatory guidance is one way to promote optimal child
      health and development and minimize disparities between children from lower socio
      economic status families and their higher income peers. However, low rates of
      attendance at and completion of parenting programs has been demonstrated.
      Understanding barriers to participation has important implications. The Obstacles
      to Engagement Scale (OES) has been used in some populations but it has not been
      evaluated for use with low-income African American samples. The aim of the
      current study is to evaluate the factor structure of the OES with a sample of low
      income, African American parents. METHOD: Parents or legal guardians with
      children aged 3-8 years completed a survey in the waiting room of a primary care
      pediatric academic practice in an urban location in the southern United States of
      America (N = 114). Almost 87% had <12th grade education and 93% of the children
      received Medicaid services. The OES was one measure from a larger study and only
      participants with complete data on the OES were included in the exploratory
      factor analysis (EFA). RESULTS: The EFA did not support the previous 4-factor
      solution (intervention demands, personal or family stressors or obstacles,
      relevance of or trust in intervention, and time and scheduling demands. Instead,
      a 3-factor statistical solution emerged but not all items held together
      conceptually. CONCLUSION: The current study supports the necessity for evaluating
      study instruments for use with specific populations. Larger samples are needed to
      disentangle the effects of educational and poverty status from race and ethnicity
      and to develop and validate instruments that are appropriate for the study
      population.

PMID- 25566518
TI  - Pomegranate Juice Enhances Healthy Lifespan in Drosophila melanogaster: An
      Exploratory Study.
AB  - Exploring innovative ways to ensure healthy aging of populations is a pre
      requisite to contain rising healthcare costs. Scientific research into the
      principles and practices of traditional medicines can provide new insights and
      simple solutions to lead a healthy life. Rasayana is a dedicated branch of
      Ayurveda (an Indian medicine) that deals with methods to increase vitality and
      delay aging through the use of diet, herbal supplements, and other lifestyle
      practices. The life-span and health-span enhancing actions of the fruits of
      pomegranate (Punica granatum L.), a well-known Rasayana, were tested on
      Drosophila melanogaster (fruitfly) model. Supplementation of standard corn meal
      with 10% (v/v) pomegranate juice (PJ) extended the life-span of male and female
      flies by 18 and 8%, respectively. When male and female flies were mixed and
      reared together, there was 19% increase in the longevity of PJ fed flies, as
      assessed by MSD, the median survival day (24.8). MSD for control and resveratrol
      (RV) groups was at 20.8 and 23.1 days, respectively. A two-fold enhancement in
      fecundity, improved resistance to oxidative stress (H2O2 and paraquat induced)
      and to Candida albicans infection were observed in PJ fed flies. Further, the
      flies in the PJ fed group were physically active over an extended period of time,
      as assessed by the climbing assay. PJ thus outperformed both control and RV
      groups in the life-span and health-span parameters tested. This study provides
      the scope to explore the potential of PJ as a nutraceutical to improve health
      span and lifespan in human beings. 

PMID- 25566519
TI  - Problem Behaviors among Israeli Undergraduate Students: Applying Jessor's Problem
      Behavior Theory among Young Adult Students.
AB  - PURPOSE: The current study tested the applicability of Jessor's problem behavior
      theory (PBT) in Ariel University. METHODS: A structured, self-reported, anonymous
      questionnaire was administered to undergraduate students. The final study sample
      included 1,360 participants (882 females and 478 males, mean age 25, SD = 2.9,
      range = 17). RESULTS: Findings indicated that the PBT was replicated in this
      sample. As shown from the hierarchal linear regression model, religiosity and
      high-academic achievements were found to be strong and significant protective
      factors that reduce risk behaviors. Among young and religious students, the
      personal vulnerability has almost no impact on involvement in risk behaviors.
      CONCLUSION: The PBT finds empirical support in this young adult undergraduate
      Israeli sample.

PMID- 25566520
TI  - Scaling up a Mobile Telemedicine Solution in Botswana: Keys to Sustainability.
AB  - Effective health care delivery is significantly compromised in an environment
      where resources, both human and technical, are limited. Botswana's health care
      system is one of the many in the African continent with few specialized medical
      doctors, thereby posing a barrier to patients' access to health care services. In
      addition, the traditional landline and non-robust Information Technology (IT)
      network infrastructure characterized by slow bandwidth still dominates the health
      care system in Botswana. Upgrading of the landline IT infrastructure to meet
      today's health care demands is a tedious, long, and expensive process. Despite
      these challenges, there still lies hope in health care delivery utilizing
      wireless telecommunication services. Botswana has recently experienced tremendous
      growth in the mobile telecommunication industry coupled with an increase in the
      number of individually owned mobile devices. This growth inspired the Botswana
      UPenn Partnership (BUP) to collaborate with local partners to explore using
      mobile devices as tools to improve access to specialized health care delivery.
      Pilot studies were conducted across four medical specialties, including
      radiology, oral medicine, dermatology, and cervical cancer screening. Findings
      from the studies became vital evidence in support of the first scale-up project
      of a mobile telemedicine solution in Botswana, also known as "Kgonafalo." Some
      technical and social challenges were encountered during the initial studies, such
      as malfunctioning of mobile devices, accidental damage of devices, and cultural
      misalignment between IT and healthcare providers. These challenges brought about
      lessons learnt, including a strong need for unwavering senior management support,
      establishment of solid local public-private partnerships, and efficient project
      sustainability plans. Sustainability milestones included the development and
      signing of a Memorandum of Understanding (MOU) between the Botswana government
      and a private telecommunications partner, the publication and awarding of the
      government tender to a local IT company, and the development and signing of a
      Memorandum of Agreement between the Ministry of Health Clinical Services
      department and the local tender winner. The initial system scale-up is scheduled
      to occur in 2014 and to ensure the project's sustainability, the system is
      aligned with the national eHealth strategy and local ownership of the project
      remains at the forefront (1). 

PMID- 25566521
TI  - Fomenting Sickness: Nocebo Priming of Residents about Expected Wind Turbine
      Health Harms.
AB  - A nocebo effect hypothesis has been proposed to explain variations in where small
      minorities of exposed residents complain about noise and health effects said to
      be caused by wind farm turbines. The hypothesis requires that those complaining
      have been exposed to negative, potentially frightening information about the
      impact of proposed wind farms on nearby residents, and that this information
      conditions both expectations about future health impacts or the etiology of
      current health problems where wind farms are already operational. This hypothesis
      has been confirmed experimentally under laboratory conditions, but case studies
      of how this process can operate in local communities are lacking. In this paper,
      we present a case study of the apparent impact of an anti-wind farm public
      meeting on the generation of negative news media and the subsequent expression of
      concerns about anticipated health and noise impacts to a planning authority
      approval hearing in Victoria, Australia. We present a content analysis of the
      negative claims disseminated about health and noise in the news media and
      available on the internet prior to the hearing, and another content analysis of
      all submissions made to the planning authority by those opposing the development
      application. 

PMID- 25566522
TI  - Vector-borne disease intelligence: strategies to deal with disease burden and
      threats.
AB  - Owing to the complex nature of vector-borne diseases (VBDs), whereby monitoring
      of human case patients does not suffice, public health authorities experience
      challenges in surveillance and control of VBDs. Knowledge on the presence and
      distribution of vectors and the pathogens that they transmit is vital to the risk
      assessment process to permit effective early warning, surveillance, and control
      of VBDs. Upon accepting this reality, public health authorities face an ever
      increasing range of possible surveillance targets and an associated
      prioritization process. Here, we propose a comprehensive approach that integrates
      three surveillance strategies: population-based surveillance, disease-based
      surveillance, and context-based surveillance for EU member states to tailor the
      best surveillance strategy for control of VBDs in their geographic region. By
      classifying the surveillance structure into five different contexts, we hope to
      provide guidance in optimizing surveillance efforts. Contextual surveillance
      strategies for VBDs entail combining organization and data collection approaches
      that result in disease intelligence rather than a preset static structure. 

PMID- 25566523
TI  - Patient Reported Delays in Seeking Treatment for Tuberculosis among Adult and
      Pediatric TB Patients and TB Patients Co-Infected with HIV in Lima, Peru: A
      Qualitative Study.
AB  - INTRODUCTION: Tuberculosis (TB) remains a significant public health challenge
      worldwide, and particularly in Peru with one of the highest incidence rates in
      Latin America. TB patient behavior has a direct influence on whether a patient
      will receive timely diagnosis and successful treatment of their illness.
      OBJECTIVES: The objective was to understand the complex factors that can impact
      TB patient health seeking behavior. METHODS: In-depth interviews were conducted
      with adult and parents of pediatric patients receiving TB treatment (n = 43),
      within that group a sub-group was also co-infected with HIV (n = 11). RESULTS:
      Almost all of the study participants recognized delays in seeking either their
      child's or their own diagnosis of their TB symptoms. The principal reasons for
      treatment-seeking delays were lack of knowledge and confusion of TB symptoms,
      fear and embarrassment of receiving a TB diagnosis, and a patient tendency to
      self-medicate prior to seeking formal medical attention. CONCLUSION: Health
      promotion activities that target patient delays have the potential to improve
      individual patient outcomes and mitigate the spread of TB at a community level.

PMID- 25566525
TI  - Community as locus for health formal and non-formal education: the significance
      of ecological and collaborative research for promoting health literacy.
AB  - The World Health Organization (2002) considers that a balance between government,
      community, and individual action is necessary for health education and promotion,
      recognizing that non-governmental organizations, local groups, and community
      institutions are central in this process. This argument reinforces the idea that
      individuals should be empowered and encouraged to make use of accurate health
      related information. This paper highlights the potential of a socio-political
      perspective for the development of health literacy within children and
      adolescents and presents two studies conducted in two daily life contexts: a
      community organization and a school. Both studies are based on methodological
      pluralism and collaborative research approaches and explore the promotion of
      health knowledge in formal and informal settings. Study 1 is based on a mixed
      methodology, using focus group discussions and questionnaires with children and
      youth with chronic diseases to explore the perceived impact of their
      participation in support associations. Study 2 presents four intensive case
      studies in schools where adolescents used community profiling, a participatory
      research methodology, to explore health rights and access to healthcare in both a
      historical and prospective vision. The results enable a deeper understanding on
      how powerful tool ccommunity resources can be for individual and collective
      empowerment on health issues. 

PMID- 25566526
TI  - Active learning by design: an undergraduate introductory public health course.
AB  - Principles of active learning were used to design and implement an introductory
      public health course. Students were introduced to the breadth and practice of
      public health through team and individual-based activities. Team assignments
      covered topics in epidemiology, biostatistics, health behavior, nutrition,
      maternal and child health, environment, and health policy. Students developed an
      appreciation of the population perspective through an "experience" trip and
      related intervention project in a public health area of their choice. Students
      experienced several key critical component elements of a public health
      undergraduate major; they explored key public health domains, experience public
      health practice, and integrated concepts with their assignments. In this paper,
      course assignments, lessons learned, and student successes are described. Given
      the increased growth in the undergraduate public health major, these active
      learning assignments may be of interest to undergraduate public health programs
      at both liberal arts colleges and research universities. 

PMID- 25566527
TI  - Facebook, quality of life, and mental health outcomes in post-disaster urban
      environments: the l'aquila earthquake experience.
AB  - BACKGROUND: An understudied area of interest in post-disaster public health is
      individuals' use of social networks as a potential determinant of quality of life
      (QOL) and mental health outcomes. A population-based cross-sectional study was
      carried out to examine whether continual use of online social networking
      (Facebook) in an adult population following a massive earthquake was correlated
      with prevalence of depression and post-traumatic stress disorders (PTSD) and QOL
      outcomes. METHODS: Participants were a sample of 890 adults aged 25-54 who had
      been exposed to the L'Aquila earthquake of 2009. Definition of "user" required a
      daily connection to the Facebook online social network for more than 1 h per day
      from at least 2 years. Depression and PTSD were assessed using the Screening
      Questionnaire for Disaster Mental Health. QOL outcomes were measured using the
      World Health Organisation Quality of Life BREF (WHOQOL-BREF) instrument. Logistic
      regression was carried out to calculate the prevalence odds ratios (POR) for
      social network use and other covariates. RESULTS: Two hundred and twenty one of
      423 (52.2%) men, and 195 of 383 (50.9%) women, had been using Facebook as social
      network for at least 2 years prior to our assessment. Social network use
      correlated with both depression and PTSD, after adjusting for gender. A halved
      risk of depression was found in users vs. non-users (POR 0.50 +/- 0.16).
      Similarly, a halved risk of PTSD in users vs. non-users (POR 0.47 +/- 0.14) was
      found. Both men and women using online social networks had significantly higher
      QOL scores in the psychological and social domains of the WHOQOL-BREF.
      CONCLUSION: Social network use among adults 25-54 years old has a positive impact
      on mental health and QOL outcomes in the years following a disaster. The use of
      social networks may be an important tool for coping with the mental health
      outcomes of disruptive natural disasters, helping to maintain, if not improve,
      QOL in terms of social relationships and psychological distress.

PMID- 25566528
TI  - Tall fescue seed extraction and partial purification of ergot alkaloids.
AB  - Many substances in the tall fescue/endophyte association (Schedonorus
      arundinaceus/Epichloe coenophiala) have biological activity. Of these compounds
      only the ergot alkaloids are known to have significant mammalian toxicity and the
      predominant ergot alkaloids are ergovaline and ergovalinine. Because
      synthetically produced ergovaline is difficult to obtain, we developed a seed
      extraction and partial purification protocol for ergovaline/ergovalinine that
      provided a biologically active product. Tall fescue seed was ground and packed
      into several different sized columns for liquid extraction. Smaller particle size
      and increased extraction time increased efficiency of extraction. Our largest
      column was a 114 * 52 * 61 cm (W * L * D) stainless steel tub. Approximately 150
      kg of seed could be extracted in this tub. The extraction was done with 80%
      ethanol. When the solvent front migrated to bottom of the column, flow was
      stopped and seed was allowed to steep for at least 48 h. Light was excluded from
      the solvent from the beginning of this step to the end of the purification
      process. Following elution, ethanol was removed from the eluate by evaporation at
      room temperature and the resulting syrup was freeze-dried. About 80% recovery of
      alkaloids was achieved with 18-fold increase in concentration of ergovaline.
      Initial purification of the dried product was accomplished by extracting with
      hexane/water (6:1, v/v). The aqueous fraction was extracted with chloroform, the
      aqueous layer discarded, after which the chloroform was removed with a resulting
      20-fold increase of ergovaline. About 65% of the ergovaline was recovered from
      the chloroform residue for an overall recovery of 50%. The resultant partially
      purified ergovaline had biological activities in in vivo and in vitro bovine
      bioassays that approximate that of synthetic ergovaline. 

PMID- 25566524
TI  - Advancing research on racial-ethnic health disparities: improving measurement
      equivalence in studies with diverse samples.
AB  - To conduct meaningful, epidemiologic research on racial-ethnic health
      disparities, racial-ethnic samples must be rendered equivalent on other social
      status and contextual variables via statistical controls of those extraneous
      factors. The racial-ethnic groups must also be equally familiar with and have
      similar responses to the methods and measures used to collect health data, must
      have equal opportunity to participate in the research, and must be equally
      representative of their respective populations. In the absence of such
      measurement equivalence, studies of racial-ethnic health disparities are
      confounded by a plethora of unmeasured, uncontrolled correlates of race
      ethnicity. Those correlates render the samples, methods, and measures
      incomparable across racial-ethnic groups, and diminish the ability to attribute
      health differences discovered to race-ethnicity vs. to its correlates. This paper
      reviews the non-equivalent yet normative samples, methodologies and measures used
      in epidemiologic studies of racial-ethnic health disparities, and provides
      concrete suggestions for improving sample, method, and scalar measurement
      equivalence. 

PMID- 25566529
TI  - Obstacles to applications of nanostructured thermoelectric alloys.

PMID- 25566530
TI  - Molecular imaging of breast cancer: present and future directions.
AB  - Medical imaging technologies have undergone explosive growth over the past few
      decades and now play a central role in clinical oncology. But the truly
      transformative power of imaging in the clinical management of cancer patients
      lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging
      agents expected to broadly expand the capabilities of conventional anatomical
      imaging methods. Molecular imaging will allow clinicians to not only see where a
      tumor is located in the body, but also to visualize the expression and activity
      of specific molecules (e.g., proteases and protein kinases) and biological
      processes (e.g., apoptosis, angiogenesis, and metastasis) that influence tumor
      behavior and/or response to therapy. Breast cancer, the most common cancer among
      women and a research area where our group is actively involved, is a very
      heterogeneous disease with diverse patterns of development and response to
      treatment. Hence, molecular imaging is expected to have a major impact on this
      type of cancer, leading to important improvements in diagnosis, individualized
      treatment, and drug development, as well as our understanding of how breast
      cancer arises. 

PMID- 25566531
TI  - Farmer to pharmacist: curcumin as an anti-invasive and antimetastatic agent for
      the treatment of cancer.
AB  - A huge number of compounds are widely distributed in nature and many of these
      possess medicinal/biological/pharmacological activity. Curcumin, a polyphenol
      derived from the rhizomes (underground stems) of Curcuma longa Linn (a member of
      the ginger family, commonly known as turmeric) is a culinary spice and
      therapeutic used in India for thousands of years to induce color and flavor in
      food as well as to treat a wide array of diseases. The origin of turmeric as
      spice and folklore medicine is so old that it is lost in legend. Curcumin has
      many beneficial pharmacological effects which includes, but are not limited with,
      antimicrobial, anti-inflammatory, antioxidant, antiviral, antiangiogenic,
      neurodegenerative diseases such as Alzheimer disease, and antidiabetic
      activities. Most importantly curcumin possesses immense antitumorigenic effect.
      It prevents tumor invasion and metastasis in a number of animal models, including
      models of lung, liver, stomach, colon, breast, esophageal cancer etc. Invasion
      and metastasis are considered as one of the hallmarks in cancer biology. The
      pertinent recent applications of curcumin as anti-invasive and antimetastatic
      agent in in vitro and in vivo and ex vivo studies as well as associated molecular
      mechanisms have been discussed in this review. Curcumin has also demonstrated the
      ability to improve patient outcomes in clinical trials. 

PMID- 25566532
TI  - Synthetic RNAs for Gene Regulation: Design Principles and Computational Tools.
AB  - The use of synthetic non-coding RNAs for post-transcriptional regulation of gene
      expression has not only become a standard laboratory tool for gene functional
      studies but it has also opened up new perspectives in the design of new and
      potentially promising therapeutic strategies. Bioinformatics has provided
      researchers with a variety of tools for the design, the analysis, and the
      evaluation of RNAi agents such as small-interfering RNA (siRNA), short-hairpin
      RNA (shRNA), artificial microRNA (a-miR), and microRNA sponges. More recently, a
      new system for genome engineering based on the bacterial CRISPR-Cas9 system
      (Clustered Regularly Interspaced Short Palindromic Repeats), was shown to have
      the potential to also regulate gene expression at both transcriptional and post
      transcriptional level in a more specific way. In this mini review, we present
      RNAi and CRISPRi design principles and discuss the advantages and limitations of
      the current design approaches. 

PMID- 25566533
TI  - The Induction of Recombinant Protein Bodies in Different Subcellular Compartments
      Reveals a Cryptic Plastid-Targeting Signal in the 27-kDa gamma-Zein Sequence.
AB  - Naturally occurring storage proteins such as zeins are used as fusion partners
      for recombinant proteins because they induce the formation of ectopic storage
      organelles known as protein bodies (PBs) where the proteins are stabilized by
      intermolecular interactions and the formation of disulfide bonds. Endogenous PBs
      are derived from the endoplasmic reticulum (ER). Here, we have used different
      targeting sequences to determine whether ectopic PBs composed of the N-terminal
      portion of mature 27 kDa gamma-zein added to a fluorescent protein could be
      induced to form elsewhere in the cell. The addition of a transit peptide for
      targeting to plastids causes PB formation in the stroma, whereas in the absence
      of any added targeting sequence PBs were typically associated with the plastid
      envelope, revealing the presence of a cryptic plastid-targeting signal within the
      gamma-zein cysteine-rich domain. The subcellular localization of the PBs
      influences their morphology and the solubility of the stored recombinant fusion
      protein. Our results indicate that the biogenesis and budding of PBs does not
      require ER-specific factors and therefore, confirm that gamma-zein is a versatile
      fusion partner for recombinant proteins offering unique opportunities for the
      accumulation and bioencapsulation of recombinant proteins in different
      subcellular compartments. 

PMID- 25566534
TI  - ncPred: ncRNA-Disease Association Prediction through Tripartite Network-Based
      Inference.
AB  - MOTIVATION: Over the past few years, experimental evidence has highlighted the
      role of microRNAs to human diseases. miRNAs are critical for the regulation of
      cellular processes, and, therefore, their aberration can be among the triggering
      causes of pathological phenomena. They are just one member of the large class of
      non-coding RNAs, which include transcribed ultra-conserved regions (T-UCRs),
      small nucleolar RNAs (snoRNAs), PIWI-interacting RNAs (piRNAs), large intergenic
      non-coding RNAs (lincRNAs) and, the heterogeneous group of long non-coding RNAs
      (lncRNAs). Their associations with diseases are few in number, and their
      reliability is questionable. In literature, there is only one recent method
      proposed by Yang et al. (2014) to predict lncRNA-disease associations. This
      technique, however, lacks in prediction quality. All these elements entail the
      need to investigate new bioinformatics tools for the prediction of high quality
      ncRNA-disease associations. Here, we propose a method called ncPred for the
      inference of novel ncRNA-disease association based on recommendation technique.
      We represent our knowledge through a tripartite network, whose nodes are ncRNAs,
      targets, or diseases. Interactions in such a network associate each ncRNA with a
      disease through its targets. Our algorithm, starting from such a network,
      computes weights between each ncRNA-disease pair using a multi-level resource
      transfer technique that at each step takes into account the resource transferred
      in the previous one. RESULTS: The results of our experimental analysis show that
      our approach is able to predict more biologically significant associations with
      respect to those obtained by Yang et al. (2014), yielding an improvement in terms
      of the average area under the ROC curve (AUC). These results prove the ability of
      our approach to predict biologically significant associations, which could lead
      to a better understanding of the molecular processes involved in complex
      diseases. AVAILABILITY: All the ncPred predictions together with the datasets
      used for the analysis are available at the following url:
      http://alpha.dmi.unict.it/ncPred/

PMID- 25566536
TI  - Three-Dimensional Kinematics of the Human Metatarsophalangeal Joint during Level
      Walking.
AB  - The objective of this study is to investigate the three-dimensional (3D)
      kinematics of the functional rotation axis of the human metatarsophalangeal (MP)
      joint during level walking at different speeds. A 12 camera motion analysis
      system was used to capture the 3D motion of the foot segments and a six force
      plate array was employed to record the simultaneous ground reaction forces and
      moments. The 3D orientation and position of the functional axis (FA) of the MP
      joint were determined based on the relative motion data between the
      tarsometatarsi (hindfoot) and phalanges (forefoot) segments. From the results of
      a series of statistical analyses, it was found that the FA remains anterior to
      the anatomical axis (AA), defined as a line connecting the first and fifth
      metatarsal heads, with an average distance about 16% of the foot length across
      all walking speeds, and is also superior to the AA with an average distance about
      2% of the foot length during normal and fast walking, whereas the FA shows a
      higher obliquity than the AA with an anteriorly more medial and superior
      orientation. This suggests that using the AA to represent the MP joint may result
      in overestimated MP joint moment and power and also underestimated muscle moment
      arms for MP extensor muscles. It was also found that walking speed has
      statistically significant effect on the position of the FA though the FA
      orientation remains unchanged with varying speed. The FA moves forwards and
      upwards toward a more anterior and more superior position with increased speed.
      This axis shift may help to increase the effective mechanical advantage of MP
      extensor muscles, maximize the locomotor efficiency, and also reduce the risk of
      injury. Those results may further our understanding of the contribution of the
      intrinsic foot structure to the propulsive function of the foot during locomotion
      at different speeds. 

PMID- 25566535
TI  - MetaDB a Data Processing Workflow in Untargeted MS-Based Metabolomics
      Experiments.
AB  - Due to their sensitivity and speed, mass-spectrometry based analytical
      technologies are widely used to in metabolomics to characterize biological
      phenomena. To address issues like metadata organization, quality assessment, data
      processing, data storage, and, finally, submission to public repositories,
      bioinformatic pipelines of a non-interactive nature are often employed,
      complementing the interactive software used for initial inspection and
      visualization of the data. These pipelines often are created as open-source
      software allowing the complete and exhaustive documentation of each step,
      ensuring the reproducibility of the analysis of extensive and often expensive
      experiments. In this paper, we will review the major steps which constitute such
      a data processing pipeline, discussing them in the context of an open-source
      software for untargeted MS-based metabolomics experiments recently developed at
      our institute. The software has been developed by integrating our metaMS R
      package with a user-friendly web-based application written in Grails. MetaMS
      takes care of data pre-processing and annotation, while the interface deals with
      the creation of the sample lists, the organization of the data storage, and the
      generation of survey plots for quality assessment. Experimental and biological
      metadata are stored in the ISA-Tab format making the proposed pipeline fully
      integrated with the Metabolights framework. 

PMID- 25566537
TI  - Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human
      Metabolism.
AB  - Intelligent in vitro models able to recapitulate the physiological interactions
      between tissues in the body have enormous potential as they enable detailed
      studies on specific two-way or higher order tissue communication. These models
      are the first step toward building an integrated picture of systemic metabolism
      and signaling in physiological or pathological conditions. However, the rational
      design of in vitro models of cell-cell or cell-tissue interaction is difficult as
      quite often cell culture experiments are driven by the device used, rather than
      by design considerations. Indeed, very little research has been carried out on in
      vitro models of metabolism connecting different cell or tissue types in a
      physiologically and metabolically relevant manner. Here, we analyze the
      physiological relationship between cells, cell metabolism, and exchange in the
      human body using allometric rules, downscaling them to an organ-on-a-plate
      device. In particular, in order to establish appropriate cell ratios in the
      system in a rational manner, two different allometric scaling models (cell number
      scaling model and metabolic and surface scaling model) are proposed and applied
      to a two compartment model of hepatic-vascular metabolic cross-talk. The
      theoretical scaling studies illustrate that the design and hence relevance of
      multi-organ models is principally determined by experimental constraints. Two
      experimentally feasible model configurations are then implemented in a multi
      compartment organ-on-a-plate device. An analysis of the metabolic response of the
      two configurations demonstrates that their glucose and lipid balance is quite
      different, with only one of the two models recapitulating physiological-like
      homeostasis. In conclusion, not only do cross-talk and physical stimuli play an
      important role in in vitro models, but the numeric relationship between cells is
      also crucial to recreate in vitro interactions, which can be extrapolated to the
      in vivo reality. 

PMID- 25566538
TI  - Toward synthesizing executable models in biology.
AB  - Over the last decade, executable models of biological behaviors have repeatedly
      provided new scientific discoveries, uncovered novel insights, and directed new
      experimental avenues. These models are computer programs whose execution
      mechanistically simulates aspects of the cell's behaviors. If the observed
      behavior of the program agrees with the observed biological behavior, then the
      program explains the phenomena. This approach has proven beneficial for gaining
      new biological insights and directing new experimental avenues. One advantage of
      this approach is that techniques for analysis of computer programs can be applied
      to the analysis of executable models. For example, one can confirm that a model
      agrees with experiments for all possible executions of the model (corresponding
      to all environmental conditions), even if there are a huge number of executions.
      Various formal methods have been adapted for this context, for example, model
      checking or symbolic analysis of state spaces. To avoid manual construction of
      executable models, one can apply synthesis, a method to produce programs
      automatically from high-level specifications. In the context of biological
      modeling, synthesis would correspond to extracting executable models from
      experimental data. We survey recent results about the usage of the techniques
      underlying synthesis of computer programs for the inference of biological models
      from experimental data. We describe synthesis of biological models from curated
      mutation experiment data, inferring network connectivity models from
      phosphoproteomic data, and synthesis of Boolean networks from gene expression
      data. While much work has been done on automated analysis of similar datasets
      using machine learning and artificial intelligence, using synthesis techniques
      provides new opportunities such as efficient computation of disambiguating
      experiments, as well as the ability to produce different kinds of models
      automatically from biological data. 

PMID- 25566539
TI  - Echographic and kinetic changes in the shoulder joint after manual wheelchair
      propulsion under two different workload settings.
AB  - Manual wheelchair users with spinal cord injury (SCI) have a high prevalence of
      shoulder pain due to the use of the upper extremity for independent mobility,
      transfers, and other activities of daily living. Indeed, shoulder pain
      dramatically affects quality of life of these individuals. There is limited
      evidence obtained through radiographic techniques of a relationship between the
      forces acting on the shoulder during different propulsion conditions and shoulder
      pathologies. Today, ultrasound is widely accepted as a precise tool in diagnosis,
      displaying particularly effectiveness in screening the shoulder rotator cuff.
      Thus, we set out to perform an ultrasound-based study of the acute changes to the
      shoulder soft tissues after propelling a manual wheelchair in two workload
      settings. Shoulder joint kinetics was recorded from 14 manual wheelchair users
      with SCI while they performed high- and low-intensity wheelchair propulsion tests
      (constant and incremental). Shoulder joint forces and moments were obtained from
      inverse dynamic methods, and ultrasound screening of the shoulder was performed
      before and immediately after the test. Kinetic changes were more relevant after
      the most intensive task, showing the significance of high-intensity activity, yet
      no differences were found in ultrasound-related parameters before and after each
      propulsion task. It therefore appears that further studies will be needed to
      collect clinical data and correlate data regarding shoulder pain with both
      ultrasound images and data from shoulder kinetics. 

PMID- 25566541
TI  - Epithelial to mesenchymal transition in tumor cells as consequence of phenotypic
      instability.
AB  - During the last years many articles have reported epithelial-to-mesenchymal
      transitions (EMT) induced by a myriad of gene products either when added to the
      cell medium or when transfected. Molecularly the EMT is characterized by the up
      regulation of transcriptional factors (EMT-TFs) repressing the epithelial gene E
      cadherin, a protein essential for the maintenance of the epithelial phenotype.
      These EMT-TFs are subjected to a complex regulation involving binary self
      stimulatory loops, allowing the possibility of the amplification of input
      signals. The capability of EMT-TFs to promote an EMT is controlled by E-cadherin
      that limits the transcription of mesenchymal genes. We discuss here the
      differences between normal and tumor epithelial cells; in the latter a partial
      inactivation of E-cadherin function enables extracellular signals to be amplified
      and induce an EMT. This tumor cell phenotypic instability is exacerbated in cell
      culture conditions. Therefore, it is likely that many of the gene products
      reported to control this transition act only in very specific cell tumor cell
      lines; thus, in cells with an unstable phenotype due to pre-existing alterations
      in E-cadherin safeguard mechanism. 

PMID- 25566540
TI  - Production of Fatty Acid-derived valuable chemicals in synthetic microbes.
AB  - Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid
      methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial
      applications including plastics, lubricants, and fuels. Currently, these
      chemicals are obtained mainly through chemical synthesis, which is complex and
      costly, and their availability from natural biological sources is extremely
      limited. Metabolic engineering of microorganisms has provided a platform for
      effective production of these valuable biochemicals. Notably, synthetic biology
      based metabolic engineering strategies have been extensively applied to refactor
      microorganisms for improved biochemical production. Here, we reviewed: (i) the
      current status of metabolic engineering of microbes that produce fatty acid
      derived valuable chemicals, and (ii) the recent progress of synthetic biology
      approaches that assist metabolic engineering, such as mRNA secondary structure
      engineering, sensor-regulator system, regulatable expression system,
      ultrasensitive input/output control system, and computer science-based design of
      complex gene circuits. Furthermore, key challenges and strategies were discussed.
      Finally, we concluded that synthetic biology provides useful metabolic
      engineering strategies for economically viable production of fatty acid-derived
      valuable chemicals in engineered microbes. 

PMID- 25566543
TI  - Multifocal hits for propagation of prion protein in sporadic Creutzfeldt-Jakob
      disease.

PMID- 25566542
TI  - Mitochondrial metabolism and the control of vascular smooth muscle cell
      proliferation.
AB  - Differentiation and dedifferentiation of vascular smooth muscle cells (VSMCs) are
      essential processes of vascular development. VSMC have biosynthetic,
      proliferative, and contractile roles in the vessel wall. Alterations in the
      differentiated state of the VSMC play a critical role in the pathogenesis of a
      variety of cardiovascular diseases, including atherosclerosis, hypertension, and
      vascular stenosis. This review provides an overview of the current state of
      knowledge of molecular mechanisms involved in the control of VSMC proliferation,
      with particular focus on mitochondrial metabolism. Mitochondrial activity can be
      controlled by regulating mitochondrial dynamics, i.e., mitochondrial fusion and
      fission, and by regulating mitochondrial calcium handling through the interaction
      with the endoplasmic reticulum (ER). Alterations in both VSMC proliferation and
      mitochondrial function can be triggered by dysregulation of mitofusin-2, a small
      GTPase associated with mitochondrial fusion and mitochondrial-ER interaction.
      Several lines of evidence highlight the relevance of mitochondrial metabolism in
      the control of VSMC proliferation, indicating a new area to be explored in the
      treatment of vascular diseases. 

PMID- 25566544
TI  - Effector memory CD4(+) T cells are associated with cognitive performance in a
      senior population.
AB  - OBJECTIVE: Immunosenescence and cognitive decline are common markers of the aging
      process. Taking into consideration the heterogeneity observed in aging processes
      and the recently described link between lymphocytes and cognition, we herein
      explored the possibility of an association between alterations in lymphocytic
      populations and cognitive performance. METHODS: In a cohort of cognitively
      healthy adults (n = 114), previously characterized by diverse
      neurocognitive/psychological performance patterns, detailed peripheral blood
      immunophenotyping of both the innate and adaptive immune systems was performed by
      flow cytometry. RESULTS: Better cognitive performance was associated with lower
      numbers of effector memory CD4(+) T cells and higher numbers of naive CD8(+) T
      cells and B cells. Furthermore, effector memory CD4(+) T cells were found to be
      predictors of general and executive function and memory, even when factors known
      to influence cognitive performance in older individuals (e.g., age, sex,
      education, and mood) were taken into account. CONCLUSIONS: This is the first
      study in humans associating specific phenotypes of the immune system with
      distinct cognitive performance in healthy aging.

PMID- 25566545
TI  - Multiple sclerosis-like lesions and type I interferon signature in a patient with
      RVCL.

PMID- 25566546
TI  - Fetal acetylcholine receptor inactivation syndrome: A myopathy due to maternal
      antibodies.
AB  - BACKGROUND: Transient neonatal myasthenia gravis (TNMG) affects a proportion of
      infants born to mothers with myasthenia gravis (MG). Symptoms usually resolve
      completely within the first few months of life, but persistent myopathic features
      have been reported in a few isolated cases. METHODS: Here we report 8 patients
      from 4 families born to mothers with clinically manifest MG or mothers who were
      asymptomatic but had elevated acetylcholine receptor (AChR) antibody levels.
      RESULTS: Clinical features in affected infants ranged from a mild predominantly
      facial and bulbar myopathy to arthrogryposis multiplex congenita. Additional
      clinical findings included hearing impairment, pyloric stenosis, and mild CNS
      involvement. In all cases, antibodies against the AChR were markedly elevated,
      although not always specific for the fetal AChR gamma subunit. There was a
      correlation between maternal symptoms; the timing, intensity, and frequency of
      maternal treatment; and neonatal outcome. CONCLUSIONS: These findings suggest
      that persistent myopathic features following TNMG may be more common than
      currently recognized. Fetal AChR inactivation syndrome should be considered in
      the differential diagnosis of infants presenting with unexplained myopathic
      features, in particular marked dysarthria and velopharyngeal incompetence.
      Correct diagnosis requires a high degree of suspicion if the mother is
      asymptomatic but is crucial considering the high recurrence risk for future
      pregnancies and the potentially treatable nature of this condition. Infants with
      a history of TNMG should be followed up for subtle myopathic signs and associated
      complications.

PMID- 25566547
TI  - Cystain C and neuropeptid Y levels in brain tissues after experimental
      subarachnoid hemorrhage.
AB  - The aim of this study was to investigate the changes in the levels of cystatin C,
      which protects neurodegeneration in the central nervous system with the
      inhibition of cysteine protease and by inducing autophagy in the pathogenesis of
      cerebral vasospasm and levels of vasoconstrictive neuropeptid Y (NPY) in the
      brain tissue homogenates of rat model of subarachnoid hemorrhage (SAH). Three
      experimental groups were used: Day 2 and Day 7 groups after SAH, and also a
      control group. There were seven Wistar albino rats in each group. SAH was
      accomplished by transclival basilar artery puncture. Rat cystatin C, rat NPY were
      determined with ELISA in brain tissue homogenates. Day 2 group showed
      significantly enhanced cystatin C values in comparision with the control group
      (P=0.048). NPY levels between the Day 2 and Day 7 groups and the control groups
      were not significantly different (P=0.315). In histopathological examination,
      there was less neuronal loss in the Day 2 group than in the Day 7 group.
      Regarding our results, it would be more valuable to measure NPY levels in
      specific brain areas. The increased cystatin C levels on the second day after SAH
      is probably a pathophysiologic mechanism to organize protease activity. 

PMID- 25566550
TI  - Raising the bar for online physician review sites.

PMID- 25566548
TI  - Cytotoxicity of anticancer aziridinyl-substituted benzoquinones in primary mice
      splenocytes.
AB  - The anticancer activity of aziridinyl-quinones is mainly attributed to their
      NAD(P)H: quinone oxidoreductase 1 (NQO1)-catalyzed two-electron reduction into
      DNA-alkylating products. However, little is known about their cytotoxicity in
      primary cells, which may be important in understanding their side effects. We
      found that the cytotoxicity of aziridinyl-unsubstituted quinones (n = 12) in mice
      splenocytes with a low amount of NQO1, 4 nmol * mg(-1) * min(-1), was caused
      mainly by the oxidative stress. Aziridinyl-benzoquinones (n = 6) including a
      novel anticancer agent RH1 were more cytotoxic than aziridinyl-unsubstituted ones
      with the similar redox properties, and their cytotoxicity was not decreased by an
      inhibitor of NQO1, dicumarol. The possible reasons for their enhanced
      cytotoxicity are discussed.

PMID- 25566549
TI  - The renaissance of vitamin D.
AB  - There is no doubt that vitamin D plays a crucial role in the maintenance of
      musculoskeletal system. But the function of this ancient molecule presumably
      ranges far beyond hormone-like regulation, as it could be generated by simple
      unicellular organisms. First, we are going to discuss the role of vitamin D as a
      global regulator of homeostasis from a historical perspective, but later we will
      focus on current views and its relevance to human physiology and pathology. Three
      milestones are defining the impact of vitamin D on science and humanity. Firstly,
      discovery that vitamin D is the cure for rickets, brought us supplementation
      programs and rapid irradiation of this devastating disease. Secondly, detail
      description of photoproduction of vitamin D, its subsequent metabolism and
      interaction with vitamin D receptor VDR, provided mechanistic background for
      future discoveries. Finally, recent large epidemiological studies provided
      indirect, but strong evidence that optimal level of vitamin D in serum has
      beneficial effects on our health and protects us from multiple diseases,
      including cancer. Furthermore, existence of alternative pathways of vitamin D
      metabolism and multiple intracellular targets broadens our understanding of its
      physiological activities and offers new and very promising tools for
      prophylactics and treatment of many diseases of civilization. Although vitamin D
      (and its derivatives) should not be regarded as a cure-all for every human
      disease, its beneficial effects on the human health have to be taken under
      consideration. 

PMID- 25566551
TI  - Physical examination of the throwing athlete's elbow.

PMID- 25566552
TI  - Office-based rapid prototyping in orthopedic surgery: a novel planning technique
      and review of the literature.
AB  - Three-dimensional (3-D) prototyping, based on high-quality axial images, may
      allow for more accurate and extensive preoperative planning and may even allow
      surgeons to perform procedures as part of preoperative preparation. In this
      article, we describe 7 cases of complex orthopedic disorders that were surgically
      treated after preoperative planning that was based on both industry-provided
      models and use of our in-house 3-D printer. Commercially available 3-D printers
      allow for rapid in-office production of a high-quality realistic prototype at
      relatively low per-case cost. Using this technique, surgeons can assess the
      accuracy of their original surgical plans and, if necessary, correct them
      preoperatively. The ability to "perform surgery preoperatively" adds another
      element to surgeons' perceptions of the potential issues that may arise. 

PMID- 25566553
TI  - Health-related quality-of-life scores, spine-related symptoms, and reoperations
      in young adults 7 to 17 years after surgical treatment of adolescent idiopathic
      scoliosis.
AB  - The goal of surgical treatment of adolescent idiopathic scoliosis (AIS) is to
      prevent disability associated with curve progression. Few investigators have
      considered whether the function of patients with AIS becomes adversely affected
      by major spine fusion surgery. Tertiary referral center patients (age, 10-17
      years) who underwent spinal deformity correction a minimum of 5 years earlier
      were identified. Scoliosis Research Society-22R (SRS-22R) and Short Form-12 (SF
      12) were administered. Data were available for 118 patients. Mean age was 14.1
      years at surgery and 26.8 years at follow-up. Mean outcome scores were 50.9 (SF
      12 physical composite summary), 49.4 (SF-12 mental composite summary), and 4.0
      (SRS-22R total). One hundred patients (85%) were working. Common symptoms
      included occasional back pain (90, 76%), limited range of motion (52, 44%),
      activity limitations (54, 46%), waistline imbalance (41, 35%), rib prominence
      (28, 24%), wound/scar problems (18, 15%), and shortness of breath (18, 15%).
      Prominent implants were reported by 11 patients (9%). Seven of 14 reoperations
      were for instrumentation removal. There was a high incidence of occasional back
      pain and activity complaints after surgery for AIS in our cohort. However, normal
      SF-12 scores suggested that these symptoms did not lower the patients' general
      health. 

PMID- 25566554
TI  - Biomechanical comparison of hamstring tendon fixation devices for anterior
      cruciate ligament reconstruction: part 1. Five femoral devices.
AB  - We conducted a study to biomechanically compare 5 femoral hamstring tendon
      fixation devices commonly used in anterior cruciate ligament reconstruction.
      Quadrupled human semitendinosus-gracilis tendon grafts were fixed into porcine
      femurs using 5 separate fixation devices. For each device, 10 specimens were
      tested (1500-cycle loading test at 50-200 N). Specimens surviving the cyclic
      loading then underwent a single load-to-failure (LTF) test. Failure mode,
      stiffness, ultimate load, and rigidity were recorded. Two of 10 Delta screw
      (Arthrex), 10 of 10 Bio-TransFix (Arthrex), 10 of 10 Bone Mulch screw
      (Arthrotek), 10 of 10 EZLoc (Arthrotek), and 10 of 10 Zip Loop (Arthrotek)
      devices completed the 1500-cycle loading test. Residual displacement was lowest
      for Bio-TransFix (4.1 mm) followed by Bone Mulch (5.2 mm), EZLoc (6.4 mm), Zip
      Loop (6.8 mm), and Delta (8.2 mm). Mean stiffness was significantly (P < .001)
      higher for Bone Mulch (218 N/mm) than for Bio-TransFix (171 N/mm), EZLoc (122
      N/mm), Zip Loop (105 N/mm), or Delta (84 N/mm). Mean LTF was significantly ( P <
      .001) higher for Bone Mulch (867 N) than for Zip Loop (615 N), Bio-TransFix (552
      N), EZLoc (476 N), or Delta (410 N). The Bone Mulch screw demonstrated superior
      strength in the fixation of hamstring grafts in the femur. Bio-TransFix was close
      behind. The Delta screw demonstrated poor displacement, stiffness, and LTF. When
      used as the sole femoral fixation device, a device with low LTF, decreased
      stiffness, and high residual displacement should be used cautiously in patients
      undergoing aggressive rehabilitation. 

PMID- 25566555
TI  - Synovial fistula after tension band plating for genu valgum correction.
AB  - Tension band plating is a commonly performed procedure to address angular
      deformities about the knee in children. We present a case of a synovial fistula
      formation after tension band plate removal, an unreported complication in the
      literature. An 11-year-old girl underwent tension band plating for genu valgum.
      After removal of the plate, she developed a synovial fistula that was confirmed
      by magnetic resonance imaging. Her knee was immobilized in extension, which
      allowed the synovial fistula to heal. The unique capsular anatomy in the knee
      provides a possible etiology. Physicians performing tension band plating should
      be aware of this complication and consider a brief period of immobilization of 3
      to 5 days after hardware removal to allow the capsular rent to heal. 

PMID- 25566556
TI  - Subtrochanteric femur fracture after removal of screws for femoral neck fracture
      in a child.
AB  - Displaced femoral neck fractures are rare in children and are associated with a
      high rate of complications. Subtrochanteric fractures after cannulated screw
      fixation of femoral neck fractures in adults are well recognized, and there are
      several reports on the topic. However, there are no reports on complications
      related to hardware or subtrochanteric fractures after removal of the screws in
      the treatment of femoral neck fractures in children. Here we report the case of a
      10-year-old boy who sustained a subtrochanteric fracture after the screw removal
      and healing that followed a femoral neck fracture. 

PMID- 25566557
TI  - The patient relations and service recovery guide: a colorful approach to handling
      upset and angry patients.

PMID- 25566558
TI  - Assessing the reading level of online sarcoma patient education materials.
AB  - Cancer patients rely on patient education materials (PEMs) to gather information
      regarding their disease. Patients who are better informed about their illness
      have better health outcomes. The National Institutes of Health (NIH) recommends
      that PEMs be written at a sixth- to seventh-grade reading level. The purpose of
      this study was to evaluate the readability of online PEMs of bone and soft-tissue
      sarcomas and related conditions. We identified relevant online PEMs from the
      following websites: American Academy of Orthopaedic Surgeons, academic training
      centers, sarcoma specialists, Google search hits, Bonetumor.org, Sarcoma
      Alliance, Sarcoma Foundation of America, and Medscape. We used 10 different
      readability instruments to evaluate the reading level of each website's PEMs. In
      assessing 72 websites and 774 articles, we found that none of the websites had a
      mean readability score at or below 7 (seventh grade). Collectively, all websites
      had a mean readability score of 11.4, and the range of scores was grade level 8.9
      to 15.5. None of the PEMs in this study of bone and soft-tissue sarcomas and
      related conditions met the NIH recommendation for PEM reading levels. Concerted
      efforts to improve the reading level of orthopedic oncologic PEMs are necessary. 

PMID- 25566559
TI  - Anemia versus transfusion: does blood conservation increase the risk of
      complications?
AB  - Orthopedic trauma patients are routinely transfused for anemia even when
      asymptomatic at rest, despite there being relatively little scientific evidence
      as to what level of anemia can be safely tolerated. Some surgeons prefer a more
      liberal approach, transfusing to keep hemoglobin (Hgb) levels at 7.0 g/dL or
      higher; others prefer a more conservative approach, allowing Hgb levels to drop
      below 7.0 g/dL. We conducted a study to determine if a more conservative approach
      might put patients at higher risk of complications of severe anemia. We
      retrospectively reviewed the cases of 104 patients who were treated by a single
      surgeon at a level I academic trauma center and who were followed up for at least
      1 year. Patients (ages 18-50 years) were divided into 2 groups by lowest Hgb
      level before first transfusion-under 7.0 g/dL and 7.0 g/dL or higher-and then by
      whether they had been transfused. Logistic regression analysis was performed. The
      primary outcome was postoperative complication. There was no increased risk of
      complication related to anemia (P = .3). However, there was a significant risk of
      complication related to transfusion (P < .01). Furthermore, there was a dose
      dependent effect with each unit transfused (P = .02). In young, healthy,
      asymptomatic orthopedic trauma patients, a more conservative transfusion strategy
      (vs a more liberal strategy) did not appear to carry higher risk. 

PMID- 25566560
TI  - Evaluation of wound healing after direct anterior total hip arthroplasty with use
      of a novel retraction device.
AB  - Use of shorter incisions in minimally invasive surgery total hip arthroplasty
      (THA) may come at the cost of poorer cosmesis, possibly a result of the excessive
      retraction needed for visualization. This may be particularly relevant in the
      direct anterior approach, in which wound-healing issues are common. We
      prospectively investigated whether a specialized ring retractor was effective in
      minimizing wound-edge trauma, as evidenced by improved scar cosmesis. Fifty
      patients having direct anterior THA were randomized to surgery with or without
      ring retractor. Incisional photographs 2, 6, and 12 weeks after surgery were
      graded by 2 blinded plastic surgeons. Wound scores and patient satisfaction with
      scar appearance were similar between groups. Our results suggest no improvement
      in wound cosmesis with use of this retraction device. 

PMID- 25566561
TI  - Severe neurologic manifestations of fat embolism syndrome in a polytrauma
      patient.
AB  - Fat embolism syndrome (FES) is most commonly diagnosed when the classic triad of
      respiratory difficulty, neurologic abnormalities, and petechial rash are present
      in the appropriate clinical setting. Neurologic manifestations can range from
      headache, confusion, and agitation to stupor and, less commonly, coma. This
      article describes a case of FES with severe neurologic sequelae without typical
      pulmonary involvement in a polytrauma patient with proximal humerus and L1
      compression fractures. The case highlights the importance of considering FES in
      the patient with deteriorating mental status in the setting of multiple
      fractures, particularly in the absence of other characteristic clinical findings.
      Early recognition allows for the anticipation of other complications, such as
      respiratory distress and the potential need for mechanical ventilation. 

PMID- 25566562
TI  - Spontaneous, chronic expanding posterior thigh hematoma mimicking soft-tissue
      sarcoma in a morbidly obese pregnant woman.
AB  - Soft-tissue sarcomas are rare and often confused for more common and benign
      disorders during diagnosis. Chronic expanding hematomas are particularly
      difficult to distinguish from soft-tissue malignancy. We describe the case of a
      morbidly obese patient with a chronic expanding hematoma in the distal posterior
      thigh whose definitive treatment was delayed 6 months because of her pregnancy
      status and inability to lie prone for open biopsy. 

PMID- 25566563
TI  - Unusual form and location for a tumor: multiosseous Ewing sarcoma in the foot.
AB  - Ewing sarcoma, as the prototype of a small round blue cell tumor of bone,
      typically affects adolescents and young adults. The most commonly involved sites
      include the diaphyses of long bones, ribs, and flat bones, such as the pelvis and
      scapula. We report a case of multifocal Ewing sarcoma involving multiple bones in
      the foot. Given the multifocal nature of the disease confined to the foot, the
      initial impression was that of osteomyelitis. We describe the histologic,
      radiologic, and diagnostic features of the tumor and outline treatment and
      prognosis. To our knowledge, this is the first report of multifocal Ewing sarcoma
      involving multiple bones in the foot. 

PMID- 25566564
TI  - The epidemic of Tommy John surgery: the role of the orthopedic surgeon.

PMID- 25566565
TI  - Inflammatory acne: new developments in pathogenesis and treatment.

PMID- 25566566
TI  - Maintaining adequate third-party compensation.

PMID- 25566567
TI  - Nodular extramammary Paget disease with fibroepitheliomatous hyperplasia.
AB  - Extramammary Paget disease (EMPD) is a rare skin condition usually found in the
      anogenital region. Histologically, EMPD may be associated with varying degrees of
      epidermal hyperplasia classified as squamous, papillomatous, or
      fibroepitheliomatous. We report a case of EMPD in a 90-year-old man who presented
      with well-demarcated plaques and a nodule in the pubic area with
      fibroepitheliomatous hyperplasia. 

PMID- 25566568
TI  - Furuncular myiasis in 2 American travelers returning from Senegal.
AB  - Furuncular myiasis caused by Cordylobia anthropophaga larvae is commonly seen in
      Africa but rarely is diagnosed in travelers returning from the sub-Saharan
      region. We report 2 cases of furuncular myiasis due to Cordylobia species in
      adolescent American travelers returning from Senegal. 

PMID- 25566569
TI  - Most common dermatologic conditions encountered by dermatologists and
      nondermatologists.
AB  - The dermatologic conditions that are most commonly encountered by
      nondermatologists are not well characterized, which can hamper efforts to train
      them in skin disease management. The purpose of this study was to identify the 20
      most common dermatologic conditions encountered by nondermatologic specialties
      (ie, emergency medicine, family practice, general surgery, internal medicine,
      otolaryngology, pediatrics). Data from the National Ambulatory Medical Care
      Survey from 2001 to 2010 were analyzed to evaluate the dermatologic diagnoses
      made by each specialty during this time period. The most common skin conditions
      reported by dermatologists were compared to those reported by nondermatologists.
      Nondermatologists evaluated 52.9% of cutaneous diseases that presented in the
      outpatient setting. Among each nondermatologic specialty included in the study,
      only 6 to 10 of the top 20 conditions overlapped with the top 20 conditions
      reported by dermatologists. This study is a retrospective review of a large
      database and only included skin conditions that were diagnosed in an outpatient
      setting. The skin conditions that most frequently presented to nondermatologists
      differed considerably from those most commonly seen by dermatologists. Because
      dermatologists often are responsible for training nondermatologists in the
      diagnosis and management of skin disease, curriculum content should reflect these
      differences to enhance the efficacy of such training opportunities. 

PMID- 25566570
TI  - Necrobiotic xanthogranuloma without a monoclonal gammopathy.
AB  - Necrobiotic xanthogranuloma (NXG) is an indolent non-Langerhans cell
      histiocytosis characterized by yellow xanthomatous plaques that tend to ulcerate.
      Necrobiotic xanthogranulomas have a predilection for the bilateral periorbital
      region and often present with consequential ophthalmic findings. Histopathology
      usually reveals a distinctive pattern of histiocytic xanthogranuloma with hyaline
      necrobiosis. Necrobiotic xanthogranuloma has been documented to have a close
      association with paraproteinemia. We report the case of a 76-year-old man with
      periorbital NXG without development of a monoclonal gammopathy. Clinically, the
      patient presented with dry eyes and substantial periorbital edema with multiple
      yellow indurated plaques. He developed the condition 30 years prior to
      presentation at which time it was initially diagnosed as xanthelasma. He
      underwent surgical excision of the lesions 10 years prior to the current
      presentation and biopsy results revealed a diagnosis of NXG. The periorbital
      lesions recurred several years prior to presentation, prompting annual computed
      tomography scans to rule out ocular invasion. Periorbital edema and plaques
      improved during a 6-month regimen of acitretin but returned to baseline just
      months after discontinuation. 

PMID- 25566571
TI  - The spectrum of pigmented purpuric dermatosis and mycosis fungoides: atypical T
      cell dyscrasia.
AB  - We report the case of a healthy 17-year-old adolescent boy with an unremarkable
      medical history who presented with an asymptomatic fixed rash on the abdomen,
      buttocks, and legs. The rash initially developed in a small area on the right leg
      2 years prior and had progressed slowly. Prior biopsies were consistent with
      pigmented purpura. Clinical examination revealed multiple annular purpuric
      patches on the abdomen, buttocks, and legs covering approximately 20% of the body
      surface area without lymphadenopathy or hepatosplenomegaly. Additional biopsies
      demonstrated changes consistent with mycosis fungoides (MF). T-cell receptor g
      gene rearrangements demonstrated clonality. The patient was diagnosed with stage
      IB MF of the pigmented purpura-like variant. The patient responded well to
      psoralen plus UVA therapy. It has been proposed that pigmented purpuric
      dermatosis (PPD) is a form of cutaneous T-cell lymphoid dyscrasia and that T-cell
      gene rearrangement studies should be obtained for prognostic evaluation in
      patients with widespread disease. In our patient, the clinical appearance of the
      lesions, pathologic findings, and gene rearrangement studies led to the diagnosis
      of MF. Until the potential for evolution of PPD to malignant disease is better
      understood, further evaluation of MF in patients with an unusual presentation of
      pigmented purpura is warranted. 

PMID- 25566572
TI  - Multiple tumors of the follicular infundibulum: a cutaneous reaction pattern?
AB  - The etiology of tumor of the follicular infundibulum (TFI) is unknown. Eruptive
      forms of TFI are rare. We present the case of a 49-year-old woman with multiple
      lesions on the arms, shoulders, trunk, buttocks, and legs of more than 3 years'
      duration. On clinical and histologic examination, a diagnosis of multiple TFI was
      made. Additionally, the patient presented with other rare remarkable features
      including severe pruritus, the Kobner phenomenon, and underlying inflammatory
      cell infiltration of the tumors. These findings strongly suggest that eruptive
      TFI may represent a kind of cutaneous reaction. 

PMID- 25566574
TI  - What is your diagnosis? Clear cell hidradenoma.

PMID- 25566573
TI  - Calcipotriene 0.005%--betamethasone dipropionate 0.064% ointment versus topical
      suspension in the treatment of plaque psoriasis: a randomized pilot study of
      patient preference.
AB  - Vehicle formulation plays a major role in patient adherence to topical psoriasis
      treatments. The objective of this study was to conduct a preliminary assessment
      of patient preference for ointment versus topical suspension formulations of
      calcipotriene 0.005%-betamethasone dipropionate 0.064% for treatment of plaque
      psoriasis. In our small cohort of 20 participants with mild to moderate plaque
      psoriasis, the topical suspension formulation was preferred over the ointment,
      though the difference was not statistically significant (P=.32). Overall, the
      topical suspension was rated as moderately appealing, while the ointment was
      rated as slightly appealing (P=.06). Subgroup analyses were limited due to the
      small sample size. The results of this study may provide clinicians with an
      alternative topical treatment of plaque psoriasis that provides the benefits of a
      combination product. In clinical practice, it may be best to offer patients both
      formulations and they can choose the product that is right for them. 

PMID- 25566575
TI  - Granular cell tumor.

PMID- 25566576
TI  - Acitretin-induced acral hemorrhagic lesions in Darier-White disease.
AB  - Darier-White disease (DD) is an autosomal-dominant inherited disease
      characterized by keratotic papules that are usually located in seborrheic areas.
      Systemic retinoids generally are first-line treatment in cases of diffuse DD. We
      report the case of an 84-year-old woman with a hypertrophic variant of DD with
      acral lesions. Oral retinoids (acitretin) were administered as a first treatment
      of DD, with good clinical results. After a few months, hemorrhagic vesicles
      developed on palmoplantar surfaces. Suspension of the therapy led to the
      disappearance of the cutaneous manifestations. 

PMID- 25566577
TI  - Late-onset nevus comedonicus on both eyelids with hypothyroidism.

PMID- 25566578
TI  - Hemorrhagic bullous lesions due to Bacillus cereus in a cirrhotic patient.

PMID- 25566579
TI  - Erythematous nodular plaque encircling the lower leg.

PMID- 25566580
TI  - Onychomycosis: current and investigational therapies.

PMID- 25566581
TI  - Multiple cutaneous abscesses revealing disseminated nocardiosis in a patient with
      chronic rheumatoid arthritis.
AB  - Nocardiosis is a challenging infection that is difficult to diagnose and treat.
      Delayed recognition and prolonged illness are major concerns. We report the case
      of a 65-year-old man who underwent treatment with corticosteroids for rheumatoid
      arthritis and then presented with multiple abscesses on the right leg. A complete
      assessment performed by the dermatologist led to the diagnosis of disseminated
      nocardiosis with involvement of the lungs and central nervous system. The
      patient's history revealed development of pulmonary disease approximately 1 year
      prior to the appearance of the skin lesions, which was not recognized by several
      specialists. Long-term antibiotic therapy was effective in treating the skin and
      central nervous system lesions, while the chest radiologic profile improved more
      slowly. 

PMID- 25566582
TI  - Stains and smears: resident guide to bedside diagnostic testing.
AB  - Dermatology residents often are on the front line when it comes to treating
      patients with complicated skin disorders, frequently seeing these cases first
      before discussing their findings and plan with an attending physician. Bedside
      testing modalities can help facilitate arriving at a diagnosis quickly, allowing
      for rapid initiation of treatment. The potassium hydroxide (KOH) preparation,
      Tzanck smear, mineral oil preparation, and Gram stain are easy to perform quickly
      and provide valuable diagnostic information. The purpose of this article is to
      consolidate these frequently used tests into a useful reference for the training
      and practicing dermatologist. 

PMID- 25566583
TI  - Large subcutaneous masses.

PMID- 25566584
TI  - Erythematous plaques on the hand and wrist.

PMID- 25566586
TI  - The atomistic mechanism of hcp-to-bcc martensitic transformation in the Ti-Nb
      system revealed by molecular dynamics simulations.
AB  - Applying the constructed Ti-Nb potentials, molecular dynamics simulations were
      conducted to investigate the martensitic transformation of Ti100-xNbx alloys (x =
      5, 10...25) from the alpha' phase (hcp) to the beta phase (bcc). It is found that
      the transformation involved four phases, i.e. alpha', alpha'', fco (face-centered
      orthorhombic), and beta phases. The structures of the obtained phases exhibit
      consistency with experimental data, verifying the validity of atomic simulations.
      The simulations not only revealed the processes of atomic displacements during
      the transformation, but also elucidated the underlying mechanism of the
      martensitic transformation at the atomic level. The martensitic transformation
      incorporates three types of coinstantaneous deformations i.e. slide, shear as
      well as extension, and the subsequent lattice constant relaxation. Furthermore,
      according to the proposed mechanism, the crystallographic correlation between the
      initial alpha' phase and the final beta phase has been deduced. The simulation
      results provide a clear landscape on the martensitic transformation mechanism,
      facilitating our comprehensive understanding on the phase transition in the Ti-Nb
      system. 

PMID- 25566585
TI  - Unravelling the impact of hydrocarbon structure on the fumarate addition
      mechanism--a gas-phase ab initio study.
AB  - The fumarate addition reaction mechanism is central to the anaerobic
      biodegradation pathway of various hydrocarbons, both aromatic (e.g., toluene,
      ethyl benzene) and aliphatic (e.g., n-hexane, dodecane). Succinate synthase
      enzymes, which belong to the glycyl radical enzyme family, are the main
      facilitators of these biochemical reactions. The overall catalytic mechanism that
      converts hydrocarbons to a succinate molecule involves three steps: (1) initial H
      abstraction from the hydrocarbon by the radical enzyme, (2) addition of the
      resulting hydrocarbon radical to fumarate, and (3) hydrogen abstraction by the
      addition product to regenerate the radical enzyme. Since the biodegradation of
      hydrocarbon fuels via the fumarate addition mechanism is linked to bio-corrosion,
      an improved understanding of this reaction is imperative to our efforts of
      predicting the susceptibility of proposed alternative fuels to biodegradation. An
      improved understanding of the fuel biodegradation process also has the potential
      to benefit bioremediation. In this study, we consider model aromatic (toluene)
      and aliphatic (butane) compounds to evaluate the impact of hydrocarbon structure
      on the energetics and kinetics of the fumarate addition mechanism by means of
      high level ab initio gas-phase calculations. We predict that the rate of toluene
      degradation is ~100 times faster than butane at 298 K, and that the first
      abstraction step is kinetically significant for both hydrocarbons, which is
      consistent with deuterium isotope effect studies on toluene degradation. The
      detailed computations also show that the predicted stereo-chemical preference of
      the succinate products for both toluene and butane are due to the differences in
      the radical addition rate constants for the various isomers. The computational
      and kinetic modeling work presented here demonstrates the importance of
      considering pre-reaction and product complexes in order to accurately treat gas
      phase systems that involve intra and inter-molecular non-covalent interactions. 

PMID- 25566587
TI  - Surface- and tip-enhanced resonant Raman scattering from CdSe nanocrystals.
AB  - Surface- and tip-enhanced resonant Raman scattering (resonant SERS and TERS) by
      optical phonons in a monolayer of CdSe quantum dots (QDs) is demonstrated. The
      SERS enhancement was achieved by employing plasmonically active substrates
      consisting of gold arrays with varying nanocluster diameters prepared by electron
      beam lithography. The magnitude of the SERS enhancement depends on the localized
      surface plasmon resonance (LSPR) energy, which is determined by the structural
      parameters. The LSPR positions as a function of nanocluster diameter were
      experimentally determined from spectroscopic micro-ellipsometry, and compared to
      numerical simulations showing good qualitative agreement. The monolayer of CdSe
      QDs was deposited by the Langmuir-Blodgett-based technique on the SERS
      substrates. By tuning the excitation energy close to the band gap of the CdSe QDs
      and to the LSPR energy, resonant SERS by longitudinal optical (LO) phonons of
      CdSe QDs was realized. A SERS enhancement factor of 2 * 10(3) was achieved. This
      allowed the detection of higher order LO modes of CdSe QDs, evidencing the high
      crystalline quality of QDs. The dependence of LO phonon mode intensity on the
      size of Au nanoclusters reveals a resonant character, suggesting that the
      electromagnetic mechanism of the SERS enhancement is dominant. Finally, the
      resonant TERS spectrum from CdSe QDs was obtained using electrochemically etched
      gold tips providing an enhancement on the order of 10(4). This is an important
      step towards the detection of the phonon spectrum from a single QD. 

PMID- 25566588
TI  - The reactivity of the active metal oxo and hydroxo intermediates and their
      implications in oxidations.
AB  - While the significance of the redox metal oxo moieties has been fully
      acknowledged in versatile oxidation processes, active metal hydroxo moieties are
      gradually realized to play the key roles in certain biological oxidation events,
      and their reactivity has also been evidenced by related biomimic models. However,
      compared with the metal oxo moieties, the significance of the metal hydroxo
      moieties has not been fully recognized, and their relationships in oxidations
      remain elusive until recently. This review summarizes the reactivity of the metal
      oxo and hydroxo moieties in different oxidation processes including hydrogen atom
      transfer, oxygen atom transfer and electron transfer, and their reactivity
      similarities and differences have been discussed as well. Particularly, how the
      physicochemical properties like metal-oxygen bond order, net charge and potential
      of a redox metal ion affect its reactivity has also been presented based on
      available data. We hope that this review may provide new clues to understand the
      origins of the enzyme's choice on them in a specific event, to explain the
      elusive phenomena occurring in those enzymatic, homogeneous and heterogeneous
      oxidations, to design selective redox catalysts and control their reactivity. 

PMID- 25566589
TI  - A comparison of the effects of hyperbaric and isobaric bupivacaine spinal
      anesthesia on hemodynamics and heart rate variability.
AB  - AIM: To compare the effects of hyperbaric and isobaric bupivacaine spinal
      anesthesia on hemodynamics and heart rate variability (HRV) in nonobstetric
      surgery. MATERIALS AND METHODS: Sixty patients were randomly allocated to 2
      groups. Group I (n = 30) received 15 mg (3 mL) of hyperbaric bupivacaine and
      Group II (n = 30) received 15 mg (3 mL) of isobaric bupivacaine for spinal
      anesthesia. Hemodynamic parameters were recorded before and after spinal
      anesthesia over 30 min. Analyses of HRV were performed on the day of surgery,
      after volume loading, and 20 min after spinal injection. Low frequency (LF)
      values, high frequency (HF) values, and LF/HF ratios were recorded. The
      incidences of hypotension and alterations of HRV parameters in both groups were
      investigated. RESULTS: The incidence ofhypotension was 26.6% and 23.3% in Groups
      I and II, respectively. There were no significant differences in the LF and HF
      values and LF/HF ratios between groups. In Group I, LF/HF ratios were
      significantly lower and HF values were significantly higher at 20 min after
      spinal anesthesia, in comparison to the baseline value (P < 0.05). CONCLUSION:
      Hyperbaric bupivacaine caused a significantly greater decrease in LF/HF ratios
      and a significantly greater increase in HF values.

PMID- 25566590
TI  - [Evaluation of voriconazole oral dosage in Japan].
AB  - Voriconazole (VRCZ), a broad-spectrum triazole, is served in two dosage forms
      injection and oral. VRCZ is difference dosage of oral and intravenous
      administration writing a medical package insert in Japan. 6 mg/kg intravenous
      injection (IV) twice daily for first day as initial loading dose, followed by 3-4
      mg/kg IV twice daily between meals is recommended. 300 mg orally twice daily for
      first day as initial loading dose, followed by 150-200 mg orally twice daily
      between meals is recommended. Patients weighing over 40 kg, 200 mg orally twice
      daily between meals is recommended. Patients weighing under 40 kg, 100 mg orally
      twice daily between meals is recommended, increase to 150 mg twice daily if
      inadequate response. This study evaluated VRCZ trough concentration and oral
      dosage in the 23 cases which administered VRCZ to analysis for TDM in Aichi
      University Hospital. Spearman rank correlation coefficient was calculated to
      examine relationships among variables. The level of statistical significance was
      set at p=0.05. All data were analyzed and processed on JMP 8 (SAS Institute
      Japan). There was a significant positive correlation between VRCZ trough
      concentration and dose/weight (r=0.47 p<0.05). In this result, VRCZ oral dosage
      is appropriate to administer dose/weight (mg/kg) twice a day as same as IV.

PMID- 25566591
TI  - [Development of a simplified assay for detection of van gene harbored enterococci
      using the automated BD MAX platform].
AB  - We developed and evaluated of multiplex real-time PCR assay for detection of
      vancomycin-resistant genes (vanA, vanB, vanC1 and vanC2/C3) using the new, fully
      automated BD MAX platform. Ct value analyses of real-time PCR simultaneous
      repeatability test have showed the usefulness; coefficient of variation: CV (%)
      were determined 2.09%, 1.72%, 1.41% and 1.52% with vanA, vanB, vanC1 and
      vanC2/C3, respectively. We also evaluated with 43 strains of enterococci were
      characterized by conventional PCR method; 4/4 for vanA-positive, 14/14 for vanB
      positive, 1/1 for vanB plus vanC1-positive, 6/6 for vanC1-positive, 4/4 for
      vanC2/C3- positive and 14/14 for all-van gene-negative strains were identified
      correctly. This assay was automatically performing before and after PCR
      operations previously done manually by operator, such as DNA extraction, sample
      dispensing and gel electrophoresis or the ethidium bromide dyeing. As a result,
      work burden and the risk of the contamination were largely reduced and were
      shortened to about half for measurement time. We conclude that this assay could
      greatly contribute to efficient and rapid detection of vancomycin-resistant
      genes.

PMID- 25566592
TI  - [Molecular genetic characterization of the Gissar virus (GSRV) (Bunyaviridae,
      Phlebovirus, Uukuniemi group) isolated from the ticks Argas reflexus Fabricius,
      1794 (Argasidae) collected in dovecote in Tajikistan].
AB  - The Gissar virus (GSRV) was originally isolated from the ticks Argas reflexus,
      Fabricius, 1794 collected in a dovecote of Gissar village in Tajikistan (38
      degrees 40' N, 68 degrees 40' E). Using electron microscopy, GSRV was classified
      to Bunyaviridae without referring to genus due to the absence of the antigenic
      relation with known bunyaviruses. In the present paper genome of GSRV was
      sequenced (MiSeq, Illumina). Molecular genetics and phylogenetic analysis showed.
      GSRV has a high level of homology with the Grand Arbaud Virus (GAV) (94% for
      nucleocapsid protein, 87.5% for RdRp, and 82% for the envelope proteins GnGc)
      isolated from the ticks A. Reflexus in a dovecote in France. GSRV and GAV have a
      narrow ecological niche associated with the icks A. Reflexus and birds
      (predominantly Columbidae). According to the conducted study, GSRV is classified
      as the topotypic for Central Asia variant of GAV, Uukuniemi group, genuses of the
      Phlebovirus (Bunyaviridae) (ID GenBank KJ425423, KJ425424, KJ425425).

PMID- 25566593
TI  - Role of levonorgestrel-releasing intrauterine system in dysmenorrhea due to
      adenomyosis and the influence on ovarian function.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy and side
      effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the
      treatment of moderate or severe dysmenorrhea associated with adenomyosis and the
      influence on ovarian function. STUDY DESIGN: The LNG-IUS was inserted into 60
      women who had moderate or severe dysmenorrhea associated with adenomyosis
      diagnosed by transvaginal sonography. A visual analogue scale (VAS) of
      dysmenorrhea, uterine volume and serum-levels of follicle stimulating hormone
      (FSH), luteinizing hormone (LH), etstradiol (E2), and prolactin (PRL) were used
      to assess the efficacy of the treatment at base- line and at six and 12 months
      after the LNG-IUS. Serum-levels ofFSH, LH, E2, and PRL were tested in pre-and
      post-insertion at six and at 12 months, respectively. Side-effects were recorded
      at every follow-up visit. RESULTS: After six and 12 months of LNG-IUS insertion,
      dysmenorrhea was obviously alleviated, and the dysmenorrhea scores decreased to
      2.6 from 0.6 (p < 0.05). The volume of uterus reduced six months after insertion
      and later, but without significant change (p <0.05). After treatment of serum, in
      terms ofFSH, LH, and E2 lev- els, compared with pre-insertion, there was no
      statistically significant difference (p > 0.01). However, the level of PRL
      markedly de- clined at six and 12 months after LNG-IUS. CONCLUSION: The LNG-IUS
      appears to be an effective method in alleviating dysmenorrhea associated with
      adenomyosis with little effect on ovarian function. It may be helpful to decrease
      the level of PRL in these patients.

PMID- 25566594
TI  - Screening of the miRNAs related to breast cancer and identification of its target
      genes.
AB  - OBJECTIVE: To predict and verify the target genes of the miRNAs related to breast
      cancer beginning from the miRNA expression profile of human breast cancer.
      MATERIALS AND METHODS: The total RNA was extracted from cancer tissues and the
      corresponding paracancerous tissues of eight breast cancer patients, and then
      miRNAs were separated. Human breast cancer cell line MDA-MB-231 and the normal
      mammary epithelial cell line HBL-100 were cultured, and the total RNA was
      extracted, respectively, with separation of miRNAs. The gene chip technology was
      used to analyze and detect the miRNAs differentially expressed in tissues and
      cancer cells. The miRNA expression profile of human breast cancer was obtained
      through chip scanning and data analysis. RESULTS: Through dual-luciferase method,
      it was verified that PDCD4 and PDCD10 were real target genes of miR-21 and miR
      200c, respectively. CONCLUSION: miR-21 and miR-200c are related miRNAs to breast
      cancer, and they are associated with the occurrence and development of breast
      cancer.

PMID- 25566595
TI  - Macrocyclic phosphazane ligands.
AB  - Inorganic macrocycles based on P(III)-N bonded frameworks can be obtained by a
      series of systematic routes, many of which parallel those commonly employed in
      the synthesis of more well known organic relatives. Such phosph(III)azane
      macrocycles exhibit a broad range of coordination behaviour, and provide new
      organically-soluble hosts, with unique steric and electronic environments. This
      short review explores designed approaches to this class of macromolecule and the
      coordination of anionic, cationic and neutral guests, and looks to the future
      development of related inorganic systems of this type.

PMID- 25566596
TI  - Surveillance is as effective as chemotherapy in stage 1 testicular cancer.

PMID- 25566597
TI  - Thoracic radiotherapy may improve survival for small cell lung cancer.

PMID- 25566598
TI  - Prostate cancer recurrence risk linked to high lipid levels.

PMID- 25566599
TI  - Author's reply: To PMID 25003676.

PMID- 25566600
TI  - Author's reply.

PMID- 25566601
TI  - Author's reply: To PMID 25003678.

PMID- 25566602
TI  - Author's reply: To PMID 25003678.

PMID- 25566603
TI  - Author's reply: To PMID 25003678.

PMID- 25566604
TI  - Rabies in Tanzania: the need for a national control programme.

PMID- 25566605
TI  - "I didn't know that ..." patient perceptions of print information, education, and
      communication related to HIV/AIDS treatment.
AB  - Improving health literacy is a necessary intervention for people with chronic
      health conditions to ensure adherence with long or life therapies and increase
      participation in self-care. While adherence is a multifactorial process,
      increasing health literacy among HIV-infected patients at all stages of living
      with HIV has been shown to improve treatment outcomes. In the era of rapid scale
      up of HIV care and treatment, little has been done to evaluate the utility of
      information, education, and communication (IEC) materials for increasing patient
      health literacy and how patients perceive such materials. Four patient-oriented
      print IEC brochures in Kiswahili were designed to be read at the clinic waiting
      areas and also carried home by patients to supplement the knowledge received from
      routine counselling during clinic visits. Brochures detail antiretroviral therapy
      and address common myths, side effects, types and management of opportunistic
      infections, and prevention of mother to child transmission of HIV. We conducted
      focus group discussions with HIV-infected patients to explore patient perceptions
      of IEC materials in the urban congested HIV care setting of Dar es Salaam,
      Tanzania. Groups of participants were recruited from eight public PEPFAR
      supported HIV care and treatment centres in the city (N = 50). In this paper we
      present the results of those focus group discussions and introduce the print IEC
      materials as a pilot intervention in a Kiswahili-speaking setting where a need
      for additional health literacy exists. Further evaluation of these materials will
      follow as the data becomes available.

PMID- 25566606
TI  - Defining malaria burden from morbidity and mortality records, self treatment
      practices and serological data in Magugu, Babati District, northern Tanzania.
AB  - Malaria morbidity and mortality data from clinical records provide essential
      information towards defining disease burden in the area and for planning control
      strategies, but should be augmented with data on transmission intensity and
      serological data as measures for exposure to malaria. The objective of this study
      was to estimate the malaria burden based on serological data and prevalence of
      malaria, and compare it with existing self-treatment practices in Magugu in
      Babati District of northern Tanzania. Prospectively, 470 individuals were
      selected for the study. Both microscopy and Rapid Diagnostic Test (RDT) were used
      for malaria diagnosis. Seroprevalence of antibodies to merozoite surface proteins
      (MSP-1(19)) and apical membrane antigen (AMA-1) was performed and the
      entomological inoculation rate (EIR) was estimated. To complement this
      information, retrospective data on treatment history, prescriptions by physicians
      and use of bed nets were collected. Malaria prevalence in the area was 6.8%
      (32/470). Of 130 individuals treated with artemisinin combination therapy (ACT),
      22.3% (29/130) were slide confirmed while 75.3% (98/130) of them were blood smear
      negative. Three of the slides confirmed individuals were not treated with ACT.
      Fever was reported in 38.2% of individuals, of whom 48.8% (88/180) were given
      ACT. Forty-two (32.3%) of those who received ACT had no history of fever. About
      half (51.1%) of those treated with ACT were children < 10 years old.
      Immunoglobulin against MSP-119 was positive in 16.9% (74/437) while against AMA-1
      was positive in 29.8% (130/436). Transmission intensity was estimated at <0.2
      infectious bites per person per year. The RDT was highly specific (96.3%) but
      with low sensitivity (15.6%). In conclusion, Magugu is a low endemic area. There
      is substantial over diagnosis, over treatment and self treatment in the
      community. The burden of malaria based on medical records is over estimated as
      was mostly presumptive. The low sensitivity of RDT reflects the low number of
      immune individuals as well as the low parasite density.

PMID- 25566607
TI  - Rational dispensing and use of artemether-lumefantrine during pregnancy in Dar es
      Salaam, Tanzania.
AB  - Artemether-Lumefantrine (ALu) is widely used for uncomplicated malaria during the
      second and third trimester of pregnancy. Because of the suspected teratogenic
      effects of artemether during the first trimester, quinine is used in early
      pregnancy unless the risks outweigh the benefits. The aim of this study was to
      assess dispensing practice of ALu in private pharmacies and knowledge of pregnant
      women regarding the use of ALu. This was a prospective-descriptive study
      involving visits to 200 private retail pharmacies (using a mystery shopper) and
      interviewing pregnant women at the municipal public hospitals in Dar es Salaam,
      Tanzania. Among the drug dispensers, 60 (30%) were pharmacists, 71(35.5%) nurse
      assistants, 34 (17%) pharmaceutical technicians and 35 (17.5%) sales persons with
      no formal education on drug dispensing. Among the dispensers, 14.5% had high
      knowledge, 38.0% had medium knowledge and 47.5% had low knowledge on the use of
      ALu during pregnancy. About thirty three percent of the drug dispensers were
      willing to dispense ALu during the first trimester of pregnancy. Sixty two
      percent of the drug dispensers indicated that ALu is the drug of choice for
      uncomplicated malaria after the first trimester of pregnancy. However, 36%
      indicated that ALu could not be used during pregnancy. A total of 200 pregnant
      women were interviewed. Among them, 16.5% were aware that ALu should not be taken
      during the first trimester of pregnancy. Only 17% of pregnant women were given
      information on the importance of taking food when using ALu, but none of them was
      given information on the importance of fatty meals when using ALu. In conclusion,
      the results show that most drug dispensers have inadequate knowledge about good
      dispensing practice of ALu in pregnancy. There is therefore a need for continuing
      training of drug dispensers regarding antimalarial drugs use in pregnancy.

PMID- 25566608
TI  - Home treatments with antipyretics and antimalarials given to underfives with
      fever in Mwanza, north-western Tanzania.
AB  - Early diagnosis and prompt treatment is the recommended management for febrile
      illness among underfives. However, improper home management may be the cause of
      delay in seeking professional health care. This cross-sectional study was
      conducted at the outpatient department of Buzuruga Health Centre in Mwanza,
      Tanzania and involved 372 children < 5 years of age. Socio-demographic data of
      caregivers and children, type and source of treatment, and duration of fever were
      recorded. A total of 283 (76.1%) febrile underfives had received different types
      of treatment at home, before presenting at the hospital. The majority received
      antipyretics (204; 72.1%), and only a few (31; 10.9%) received antimalarials. The
      major sources of drugs were local drug stores (270; 94.7%). Duration of fever > 1
      day (OR = 2.69; 95% CI: 1.95-3.70; P < 0.001), low grade fever (OR = 4.37, 95%
      CI: 2.60-7.35; P < 0.001) and fever accompanied with other major complaints (OR =
      1.14, 95% CI: 1.05 - 1.23; P = 0.002) were significantly associated with prompt
      home medication before presenting to the health centre. In logistic regression
      analysis, duration of fever, low-grade fever and the presence of other symptoms
      remained significant predictors to receive antimalarial and or antipyretic drugs.
      In conclusion, home treatments with antipyretics and antimalarials in preschool
      children are common in Mwanza. Management of fevers may be improved by educating
      caregivers on community standard case definition of malaria while emphasizing the
      importance of early seeking of health facility services.

PMID- 25566609
TI  - Antibacterial and cytotoxic activities of Terminalia stenostachya and Terminalia
      spinosa.
AB  - Plants that belong to the Combretaceae family have long history of use in the
      traditional medicine systems of Africa and Asia for treatment of diseases and
      conditions associated with HIV/AIDS-opportunistic infections. The objective of
      this study was to investigate the biological activities of extracts of Terminalia
      stenostachya Engl. & Diels and Terminalia spinosa Engl. (Combretaceae), to verify
      the rationale for their use by traditional health practitioners in the treatment
      of HIV/AIDS patients in Tanzania. Extracts of the leaves, stem barks and roots of
      T. stenostachya and extracts of stem barks and roots of T. spinosa have all shown
      strong activity against a number of standard microbial strains including
      Mycobacterium madagascariense and Mycobacterium indicus pranii, Streptococcus
      faecalis, Staphylococcus aureus, Vibrio cholera, Bacillus anthracis, Bacillus
      subtilis, Klebsiella pneumoniae, Salmonella typhi, Pseuodomonas aeruginosa and
      Escherichia coli. All extracts from the two plant species showed strong
      antimycobacterial activity against test organisms. The stem and root bark
      extracts were more active than leaves against both gram positive and negative
      bacteria. With the exception of two extracts from stem barks of T. spinosa, all
      other extracts from T. stenostachya and T. spinosa that were tested exhibited
      less activity against brine shrimp larvae with LC50 values >= 100 MUg/mL compared
      to cyclophosphamide, a standard anticancer drug. These results provide an
      indication that these plants may possess therapeutically potent antimicrobial
      compounds worth further development.

PMID- 25566610
TI  - Cancer distribution pattern in south-western Nigeria.
AB  - The burden of cancer in Nigeria is appreciable with about 100,000 new cancer
      cases being reported in the country each year. This study aimed to determine the
      level of occurrence and pattern of distribution of different cancer types in two
      major functional cancer registries in south-western Nigeria. A desk review of the
      level of occurrence and pattern of distribution of different cancer types in
      Lagos and Ibadan cancer registries over a 5 year period (2005-2009) was carried
      out. The results obtained showed a total number of 5094 cancer patients
      registered between 2005 and 2009 in both Lagos (60%) and Ibadan (40%) cancer
      registries. Breast cancer accounted for the majority of cases (20.2%), followed
      by cervical cancer (7.9 %), fibroid (4.4%), liver (4.4%), stomach (4.3%), brain
      (3.9%), pancreas (3.8%), prostate (3.3%), lung (3.0%) and cancer of the kidney
      (0.7%). There were significant differences (P <= 0.05) in the level of occurrence
      between cancers of the breast, cervix, prostate, liver, ovary and all other
      cancers. Liver cancer (147; 77) and bone cancer (91; 37) were predominant in
      females than males while lung cancer (89; 65), stomach cancer (112; 109), and
      kidney cancer (24; 14) were predominant in males than females. In conclusion, the
      findings of this study provide insights to cancer epidemiology in the western
      region of Nigeria. This study confirms earlier findings that breast, prostate,
      liver and cervical cancers account for the majority of cases of cancers in
      Nigeria. Thus, there is need to organize a wider scale suitable methods for early
      detection of these diseases.

PMID- 25566611
TI  - Mouse cytokine profile skewed towards Th2 in pregnancy during infection with
      Brucella abortus S19 strain.
AB  - The two classes of cytokines Th1 and Th2 determine the type of immune response
      elicited. The Th2 immune response is associated with successful pregnancy.
      Brucellosis is an intracellular bacterium that elicits the Th1 response and is
      known to cause spontaneous abortion in mammalian species. This study sought to
      determine if Brucella infection causes spontaneous abortion by causing the
      circulating cytokine profile be Th1 dominant during pregnancy. Forty-eight Swiss
      white mice were used in this murine model and the S19 strain of Brucella abortus
      was used in as the infective agent. Pregnant mice in the test group were injected
      intraperitoneally with 10(5-8) CFU of Brucella and cytokine profile evaluated
      over the three trimesters of pregnancy. Pregnant mice in the control group were
      left to go through normal pregnancy and their cytokine profile evaluated over the
      three trimesters of pregnancy. Cytokines in serum samples were analyzed by
      Cytometric Bead Array. The data was analyzed using the Paired T- test and p <
      0.05 was considered significant. IFN-gamma and TNF-alpha represented the Th1
      cytokines while IL-4 and IL-5 represented the Th2 cytokines. None of the mice in
      the test group had spontaneous abortion. IFN-gamma and TNF-alpha had no
      significant differences between cytokine levels for infected and uninfected
      groups in all 3 trimesters of pregnancy. IL-4 levels had significant differences
      in all three trimesters of pregnancy (t = 13, P = 0.036, 0.0071 and 0.0277). IL-5
      levels had significant differences second trimester (t = 14, P = 0.0075). The
      cytokine profile was robustly Th2. In conclusion, Brucella abortus cannot cause
      spontaneous abortion by altering the mouse cytokine profile towards Th1 in
      pregnancy. Elevated IL-4 levels with corresponding suppression of IFN-gamma can
      be used as a marker for successful pregnancy in Brucellosis.

PMID- 25566612
TI  - Intestinal schistosomiasis associated with intussusception: a case report.
AB  - We report a case of intestinal schistosomiasis associated with iliocaecal
      intussusception resulting from obstructions of the terminal part of the ileum by
      schistosome egg-induced fibrosis. A 7-year-old boy presented with the history of
      abdominal pain and difficulties in passing stool for two months. Ultrasound
      examination revealed doughnut signs characterized with multiple concentric rings
      at the lateral abdomen, and the bowel loop appeared distended. Exploratory
      laparatomy confirmed intussusception of the terminal part of the ileum into the
      caecum, extending to the ascending colon. Hemicolectomy and end-to-end
      iliocolostomy was performed. Histological examination of the resected bowel
      revealed Schistosoma mansoni eggs within the mucosa, submucosa of the ileum,
      caecum and ascending colon, granulomatous inflammation with foreign body giant
      cells accompanied by fibrosis and eosinophilic infiltrate into the mucosa.
      Postoperatively, the patient recovered well. There may have been a synergistic
      effect of schistosomiasis with other underlying conditions, leading to
      intussusception. In conclusion, it is important to consider S. mansoni infection
      as a differential diagnosis for intestinal obstruction in endemic areas.

PMID- 25566613
TI  - Massive vulval oedema in multiple pregnancies at Bugando Medical Centre: case
      reports.
AB  - Massive vulval oedema is not common during pregnancy, but when it develops, it
      often is associated with patient discomfort and management challenges. Two
      pregnant women presented to Bugando Medical Centre in Mwanza, Tanzania, with
      massive swelling of the vulva at 39 weeks and 32 weeks of gestation. Both women
      were found to have multiple gestations. Despite medical management, there was no
      resolution of the oedema. In both cases, vulval oedema subsided after being
      delivered by caesarean section. Major vulval oedema during pregnancy is a serious
      issue. If not treated appropriately, it can lead to major complications of
      increased blood loss and poor wound healing. Abdominally delivery is the
      preferred mode of delivery at our institution for massive vulval oedema.

PMID- 25566614
TI  - [Liu Ping--an explorer in integrative medical hepatologist].

PMID- 25566615
TI  - [Kuntai capsule combined with gonadotropin releasing hormone agonist in treatment
      of moderate-severe endometriosis: a clinical observation].
AB  - OBJECTIVE: To observe the effect of Kuntai Capsule (KC), a Chinese patent
      medicine, in add-back therapy for gonadotropin-releasing hormone agonist (GnRH-a)
      treatment for moderate-severe endometriosis (EM). METHODS: Totally 100 patients
      suffering from stage III/IV EM, who were confirmed by laparoscopic surgery were
      randomly assigned to the GnRH-a group (A) and the KC combined GnRH-a group (B),
      50 in each group. Patients in Group A were hypodermically injected with goserelin
      (3.6 mg), once per 4 weeks. Those in Group B additionally took KC, 4 pills each
      time, three times per day. The therapeutic course for all was 12 weeks. Serum
      levels of estradiol (E2), follicle stimulating hormone (FSH), bone gamma
      carboxyglutamic-acid-containing proteins (BGP) were measured respectively.
      Kupperman Menopausal Index (KMI) and bone mineral density (BMD) of the lumbar
      vertebra were also compared between the two groups. RESULTS: Serum levels of E2
      and FSH both significantly decreased in the two groups at week 12 of the
      treatment (P < 0.05), when compared with pre-treatment. Compared with before
      treatment in the same group, KMI increased in the two groups (P < 0.05). Compared
      with before treatment in the same group, BMI decreased in the two groups with no
      statistical difference (P > 0.05). Serum BGP increased after 12-week treatment (P
      < 0.05). Compared with Group A after treatment, serum levels of E2 and FSH both
      significantly increased in Group B (P < 0.05). There was no statistical
      difference in KMI between the two groups (P > 0.05). As for the incidence of
      menopausal symptoms, better effects in improving symptoms such as hot flashes,
      sleep disorders, and vaginal dryness were obtained in Group B than in Group A (P
      < 0.05). There was no significant difference in the post-pre-treatment difference
      of BMI between the two groups, but with statistical post-pre-treatment difference
      in the BGP level (P < 0.05). CONCLUSIONS: HKC combined GnRH-a could effectively
      reduce GnRH-a treatment induced partial low estrogen symptoms, improve increased
      serum BGP levels after GnRH-a therapy.

PMID- 25566616
TI  - [Effect of electro-acupuncture on clinical outcomes and ovarian hyperstimulation
      syndrome in in vitro fertilization and embryo transplantation].
AB  - OBJECTIVE: To observe the effect of electro-acupuncture (EA) on clinical outcomes
      and the occurrence of ovarian hyperstimulation syndrome (OHSS) in in vitro
      fertilization and embryo transplantation. METHODS: Totally 109 patients who
      routinely received in vitro fertilization/intracytoplasmic sperm injection
      (IVF/ICSI) at Reproductive Center were assigned to the control group (56 cases)
      and the EA group (53 cases) according to even and odd-numbered date. Patients in
      the control group received controlled ovarian hyperstimulation (COH) referring to
      GnRH-a long protocol. On the basis of COH, those in the EA group received EA from
      the day of Gn injection to the day of embryo transfer. Estradiol (E2), vascular
      endothelial growth factor (VEGF), interleukin-6 (IL-6), and angiotensin (AT) II
      were measured in all patients on the day of hCG injection, the day of ovum pick
      up (OPU), and the day of embryo transfer (ET), respectively. The oocyte retrieval
      rate, good quality embryo rate, clinical pregnancy rate, the abortion rate, and
      the occurrence of OHSS were compared between the two groups. RESULTS: Compared
      with the control group, serum E2 levels on the day of OPU and the day of ET were
      significantly lower in the EA group (P < 0.05). On the day of OPU levels of VEGF
      and IL-6 also significantly decreased (P < 0.05). Serum levels of VEGF and IL-6
      reached the highest line on the day of hCG in the two groups, and then showed a
      decreasing trend. Compared with the control group at the same time point, serum
      levels of VEGF and IL-6 obviously decreased on on the day of OPU, hCG, and ET (P
      < 0.05). The occurrence of OHSS and the canceling rate of transplant cycle were
      significantly lower in the EA group than in the control group (P < 0.05).
      CONCLUSIONS: EA, as an adjunctive therapy, could reduce the occurrence of OHSS in
      IVF. Besides, it did not decrease good embryo rates and pregnancy rates in IVF
      ET, which might be associated with lowering local vascular permeability of
      ovaries.

PMID- 25566618
TI  - [Treatment of adenomyosis patients by bushen huoxue sanyu decoction: a clinical
      study].
AB  - OBJECTIVE: To observe the clinical efficacy of Bushen Huoxue Sanyu Decoction
      (BHSD) in treatment of adenomyosis (AM) patients. METHODS: Seventy AM patients of
      Shen deficiency blood stasis syndrome (SDBSS) were randomly assigned to two
      groups, the CM treatment group (50 cases) and the Mirena group (20 cases).
      Patients in the CM treatment group were treated with BHSD, one dose per day.
      Levonorgestrel intrauterine system (Mirena) was placed in the uterine cavity of
      those in the Mirena group. The therapeutic course for all was 3 months. Changes
      of dysmenorrhea, menstrual quantity, SDBSS, CM syndrome, uterine volume, and
      serum CA125 levels were observed before and after treatment. RESULTS: Compared
      with before treatment in the same group, scores for dysmenorrhea integral, scores
      for menstrual quantity, scores for SDBSS, and scores for CM syndrome all
      decreased in the two groups after treatment (P < 0.01). Compared with before
      treatment in the same group, the uterine volume was reduced after treatment in
      the two groups (P < 0.05) and serum carbohydrate antigen CA125 levels decreased
      between the two groups (P < 0.05, P < 0.01). Compared with the Mirena group,
      scores for dysmenorrhea integral increased and scores for SDBSS decreased in the
      CM treatment group (P < 0.01, P < 0.05). There was no statistical difference in
      the uterine volume or serum carbohydrate antigen CA125 levels (P > 0.05).
      CONCLUSIONS: BHSD could effectively alleviate main symptoms of AM patients of
      QSBSS such as dysmenorrhea, profuse menstrual blood volume, and increased uterine
      volume, and lower scores for QSBSS and the total score for CM syndrome.

PMID- 25566617
TI  - [Effect of modified cangfu daotan decoction in improving endometrial receptivity
      in infertility patients with polycystic ovarian syndrome].
AB  - OBJECTIVE: To study the effect and potential mechanism of Modified Cangfu Daotan
      Decoction (MCDD) on endometrial receptivity in infertility patients with
      polycystic ovarian syndrome (PCOS). METHODS: Totally 298 women having normal
      ovulation who underwent artificial insemination were recruited as the control
      group, and they received no drug therapy. Another 355 infertility patients with
      PCOS who received ovarian stimulation therapy were recruited as the treatment
      group. Then they were further assigned to the treatment group I (195 cases) and
      the treatment group II (160 cases) according to random digit table. Patients in
      the treatment group I received clomiphene (CC) + human menopause gonadotropin
      (HMG) +human chorionic gonadotropin (HCG), while those in the treatment group II
      received CC + HMG + HCG and additionally took modified MCDD. The therapeutic
      course for all was three menstrual cycles. The pregnancy ratio, the endometrial
      thickness, and spiral artery pulsatility index (PI), resistance index (RI), and
      homeostasis model assessment-insulin resistance (HOMA-IR) were measured.
      Furthermore, the uncoupling protein 2 (UCP2) level was tested by Western blot.
      RESULTS: Compared with the control group, the endometrial thickness decreased and
      PI and RI increased in the treatment group I (all P < 0.05). Compared with the
      treatment group I , the endometrial thickness increased and PI and RI decreased
      in the treatment group II (all P < 0.05). Compared with before treatment, HOMA-IR
      levels were significantly decreased in the treatment group II after treatment (P
      < 0.05). Compared with the control group before treatment, the HOMA-IR level
      increased in the treatment group I and the treatment group II before treatment (P
      < 0.05). Compared with the control group after treatment, the HOMA-IR level
      increased in the treatment group I (P < 0.05). But there was no statistical
      difference in the post-treatment HOMA-IR level between the control group and the
      treatment group II (P < 0.05). Compared with the control group, the post
      treatment UCP2 level was increased in the treatment group II (P < 0.05). After
      one year follow-up, the pregnancy rate was 16.1% (48/298) in the control group,
      23.1% (37/160) in the treatment group I, and 33.8% (66/195) in the treatment
      group II. Compared with the control group, the pregnancy rate was significantly
      increased in the treatment group II (P < 0.05). CONCLUSION: MCDD was found to be
      capable of increasing the pregnancy rate of infertility patients with PCOS, which
      might be associated with improving endometrial blood flow and insulin resistance,
      increasing the UCP2 expression, and finally improving the endometrial
      receptivity.

PMID- 25566619
TI  - [Effect of yougui formula granule on ovarian granulosa cells gene expression
      profiles in IVF patients of shen yang deficiency syndrome].
AB  - OBJECTIVE: To observe the effect of Yougui Formula Granule (YFG) on ovarian
      granulosa cells gene expression profiles in in vitro fertilization-embryo
      transfer (IVF-ET) patients of Shen yang deficiency syndrome (SYDS) from the
      viewpoint of genomics. METHODS: Totally 72 infertility patients undergoing IVF-ET
      were randomly assigned to the treatment group and the control group according to
      random digit table, 36 in each group. Patients in the treatment group took YFG
      combined gonadotropin (Gn), while those in the control group took placebos
      combined Gn. All medication lasted for 3 menstrual cycles before IVF. With high
      throughput gene sequencing technology, gene expression profiles of ovarian
      granulosa cells in the two groups were analyzed to explore the difference by gene
      ontology (GO) enrichment analysis and kyoto encyclopedia of genes and genomes
      (KEGG) pathway analysis. RESULTS: Ovarian granulosa cell gene expression profiles
      from the follicular fluid showed, when compared with the control group, 391
      differential genes were found in the syndrome-control group, 153 down-regulated
      and 238 upregulated. Enrichment of differentially expressed cellular location and
      molecular function of genes involved cell proliferation and apoptosis associated
      cyclin, protein ubiquitination, construction of microtubules and microfilament,
      mitochondrial function and energy-related factors, regulatory factors for hormone
      synthesis. Participated pathways involved energy metabolism pathway and
      transforming growth factor-beta (TGF-beta) signaling pathway. CONCLUSIONS: There
      existed significant difference in gene expression profiles of ovarian granulosa
      cells between the treatment group and the control group. Differentially expressed
      genes involved in biological processes correlates with Shen yang deficiency
      induced proliferation of germ cells, confused apoptosis, and hindered process
      during which mitochondria produced energy.

PMID- 25566620
TI  - [Efficacy of yindan xinnaotong soft capsule on cerebral infarction
      reconvalescents of static blood blocking collaterals syndrome: a randomized
      controlled study].
AB  - OBJECTIVE: To evaluate the efficacy and safety of Yindan Xinnaotong Soft Capsule
      (YXSC) on cerebral infarction (CI) reconvalescents of static blood blocking
      collaterals syndrome (SBBCS). METHODS: Totally 118 CI reconvalescents of SBBCS
      were randomly assigned to the test group (treated by YXSC) and the control group
      [treated by Naoxintong Capsule (NC)], 59 in each group. The therapeutic course
      for all was 12 weeks. Changes of National Institute of Health Stroke Scale
      (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), Chinese medical
      syndrome scores, and serum lipid indices were observed in the two groups.
      RESULTS: Compared with the control group, the patient proportion of improving
      activities of daily life by more than or equal to 75 score was elevated (80.7% vs
      62.5%; P < 0.05). Compared with before treatment in the same group, the NIHSS
      score decreased at post-treatment 4, 8, and 12 weeks in the two groups (P <
      0.05). The patient proportion of dropped NIHSS score by more than or equal to 5
      score was lowered (80.7% vs 57.14%), and the total effective rate of improving
      Chinese medical syndromes was superior in the test group after 12-week treatment
      (89.47% vs 71.43%, all P < 0.05). After 12-week treatment there was no
      statistical difference in the patient proportion of lowering mRS lower than or
      equal to 2 or blood lipids between the two groups (P > 0.05). CONCLUSION: YXSC
      showed certain effect in improving activities of daily life, attenuating the
      neurological impairment, and elevating the total effective rate of improving
      Chinese medical syndromes in CI patients in the recovery stage.

PMID- 25566621
TI  - [Correlation study on Chinese medical syndrome types of chronic hepatitis B
      patients and HLA-DR13 gene, BCP mutation, and T-lymphocyte subsets].
AB  - OBJECTIVE: To explore the correlation between the HLA-DR13, basic core promoter
      (BCP), changes of T lymphocyte subset and clinical Chinese medical syndromes of
      chronic hepatitis B (CHB). METHODS: Totally 102 CHB patients were syndrome typed
      as Gan depression Pi deficiency syndrome (GDPDS), Pi-Shen yang deficiency
      syndrome (PSYDS), Gan-gallbladder dampness heat syndrome (GGDHS), Gan-Shen yin
      deficiency syndrome (GSYDS), and static blood blocking collaterals syndrome
      (SBBCS). Besides, 30 healthy subjects were recruited as the normal control group.
      The blood HBV-DNA level and HLA-DR13 gene were detected with real time
      fluorescent PCR. The expression of CD4+ and CD8+ in T lymphocytes was detected
      using flow cytometry. The mutation of serum A1762T/G1764A was detected using PCR
      sequencing. Hepatitis Be antigen (HBeAg) was detected with ELISA, and correlation
      between various Chinese medical syndrome types and objective indicators were
      analyzed. RESULTS: There was no statistical difference in HBV-DNA quantitative
      results among various syndrome types (P > 0.05). HBeAg positive rate was higher
      in GDPDS than in other syndrome types (P < 0.05). It was sequenced as GDPDS >
      GSYDS > SBBCS > GGDHS > PSYDS. Compared with the normal control group,
      percentages of CD3+ and CD3+ CD4+ were lower in PSYDS (P < 0.05). The ratio of
      CD3+ CD4+/CD3+ CD8 was lower in GGDHS and PSYDS than in the normal control group
      (P < 0.05). There was no statistical difference in the CD3+ CD8+ percentage among
      various syndrome types (P > 0.05). The quantitation of HLA-DR13 gene was lower in
      GDPDS and GSYDS than in the normal control group (P < 0.05). The positive rate of
      BCP mutation was higher in GSYDS than in other syndrome types (P < 0.05).
      CONCLUSION: Co-detection results of HLA-DR13 and BCP could be used as reference
      indices of Chinese medical syndrome typing of CHB.

PMID- 25566622
TI  - [Manifestations of rheumatoid arthritis patients of cold syndrome and heat
      syndrome using wrist ultrasound].
AB  - OBJECTIVE: To explore distinctive manifestations of rheumatoid arthritis (RA)
      patients of cold syndrome and heat syndrome using wrist joints ultrasound.
      METHOD: s Totally 65 RA patients were syndrome typed as cold syndrome (29 cases,
      cold-damp blockage syndrome) and heat syndrome (36 cases, damp-heat obstruction
      syndrome). Grey-scale synovitis, power doppler (PD) signals, tenosynovitis, and
      bone erosion were observed using wrist ultrasound. Distinctive manifestations of
      cold syndrome and heat syndrome were analyzed using wrist ultrasound. RESULTS: In
      RA patients of cold syndrome, the positive rate of synovitis, PD, tenosynovitis,
      and bone erosion was 51.72%, 20.68%, 51.72%, and 37.93%, respectively, while they
      were 97.22%, 91.67%, 75.0%, and 63.89%, respectively in RA patients of heat
      syndrome. Compared with patients of cold syndrome, the positive rate of
      synovitis, PD, and bone erosion increased in patients of heat syndrome (P < 0.01,
      P < 0.01, P < 0.05). There was no statistical difference in the positive rate of
      tenosynovitis between the two groups (P > 0.05). Compared with the cold syndrome
      group, there was statistical difference in the constituent ratio of synovitis,
      PD, and bone erosion in the heat syndrome group (P < 0.01, P < 0.01, P < 0.05),
      but with no statistical difference in the constituent ratio of tenosynovitis (P >
      0.05). Results of the ROC curve showed that the sensitivity was 86.1% and the
      specificity was 62.1% in judging heat syndrome, when the total score of synovitis
      in two wrists was more than 1.5; the sensitivity was 80.0% and the specificity
      was 93.1% in judging heat syndrome, when the total score of PD in two wrists was
      more than 1.5. CONCLUSIONS: Positive rates of synovitis, PD, and bone erosion
      were significantly higher in RA patients of heat syndrome than those of cold
      syndrome. Especially serious manifestations were more often seen in RA patients
      of heat syndrome. The total score of synovitis or PD in the two wrist joints
      higher than 1.5 was characteristic manifestations of heat syndrome using wrist
      ultrasound.

PMID- 25566623
TI  - [Differential expression of microRNA in chronic hepatitis B patients of pi-wei
      dampness-heat syndrome and of gan depression Pi deficiency syndrome: a primary
      research].
AB  - OBJECTIVE: To explore different microRNA expression profiles between chronic
      hepatitis B (CHB) patients of Pi-Wei dampness-heat syndrome (PWDHS) and Gan
      depression Pi deficiency syndrome (GDPDS). METHODS: By applying gene chip
      technology, blood samples from CHB patients of PWDHS (3 cases), GDPDS (3 cases),
      and healthy volunteers (3 cases) were withdrawn and microRNA detected. The
      microRNA was screened and functional analyses performed by using SAS system.
      RESULTS: Totally 77 microRNAs with differential expression were screened from CHB
      patients of PWDHS and healthy volunteers, including 60 up-regulated microRNAs and
      17 down-regulated microRNAs. Functions of target genes were mainly associated
      with transcription factors, gas exchange, adverse stimulating, regulation of
      enzyme activities, developing of the immune system, and the process of actin
      filaments. Totally 41 microRNAs with differential expression were screened from
      CHB patients of GDPDS and healthy volunteers, including 32 up-regulated microRNAs
      and 9 down-regulated microRNAs. Functions of target genes were mainly associated
      with binding to nucleotide or chromatin, inhibition and activation of
      transcription, biosynthesis, regulation of metabolic process, regulation of
      enzyme activities, developing of the immune system, the process of actin
      filaments, and IL-12. Totally 6 microRNAs with differential expression were
      screened from CHB patients of PWDHS and CHB patients of GDPDS, including 1 up
      regulated microRNA and 5 down-regulated microRNAs. Functions of target genes were
      mainly associated with transmembrane transport, regulation of transcription
      factors, metabolism of hormones, developing of the immune system, the process of
      actin filaments, regulation of metabolic process, response to exterior
      stimulation, and so on. CONCLUSION: There existed differentially expressed
      microRNAs (spectrum) between CHB patients of PWDHS and CHB patients of GDPDS.

PMID- 25566624
TI  - [Effect of activating blood circulation or activating blood circulation and
      detoxication on platelet activation, inflammation, and coagulation status in
      acute myocardial infarction rats].
AB  - OBJECTIVE: To observe the effect of activating blood circulation drugs or
      activating blood circulation and detoxication drugs on indices of platelet
      activation, inflammation, and coagulation status correlated with blood-stasis and
      toxin in acute myocardial infarction rats. METHODS: Totally 100 male SD rats were
      randomly divided into the sham-operation group, the model group, the activating
      blood circulation group, the activating blood circulation and detoxication group,
      and the metoprolol group, 20 in each group. Rats in the activating blood
      circulation group were administered with Xiongshao Capsule at the daily dose of
      0.39 g/kg. Rats in the activating blood circulation and detoxication group were
      administered with Xiongshao Capsule (at the daily dose of 0.39 g/kg) and
      Huanglian Capsule (at the daily dose of 0.135 g/kg). Rats in the metoprolol group
      received metoprolol at the daily dose of 2.25 mg/kg. And rats in the rest two
      groups were administered with normal saline. All medication lasted for 3
      successive weeks. After the last administration, the rat model of acute
      myocardial infarction was prepared by ligation of left anterior descending
      artery. No ligation was given to rats in the sham-operation group. Animals were
      sacrificed 24 h after modeling. Tumor necrosis factor-alpha (TNF-alpha), beta
      thromboglobulin (beta-TG), platelet alpha granule membrane protein-140 (GMP-140),
      11 dehydro-thromboxane B2 (11-DH-TXB2), fibrinopeptide A (FPA), antithrombin III
      (AT-III), and D-dimer (DD) were detected by ELISA. The mRNA expression of TNF
      alpha was tested by RT-PCR. RESULTS: Platelet activation parameters were
      significantly increased in the model group, when compared with the sham-operation
      group (P < 0.01). Compared with the model group, all indices (except GMP-140 in
      the metoprolol group) obviously decreased in each medicated group (P < 0.01, P <
      0.05). Besides, beta-TG and 11-DH-TXB2 were superior in the activating blood
      circulation and detoxication group to that of the metoprolol group (P < 0.05).
      But 11-DH-TXB2 was also obviously superior in the activating blood circulation
      and detoxication group to that of the activating blood circulation group (P <
      0.05). Compared with the sham-operation group, an obviously hypercoagulable state
      was obviously shown in the AMI model group, with significantly increased FPA and
      DD (P < 0.05 or 0.01) and significantly decreased AT III (P < 0.01). Compared
      with the model group, the FPA level significantly decreased in each medicated
      group (P < 0.01), and the AT III level significantly increased in the activating
      blood circulation group and the activating blood circulation and detoxication
      group (both P < 0.01). The level of DD obviously decreased in the activating
      blood circulation and detoxication group (P < 0.01). Besides, the 3 indices were
      superior in the activating blood circulation and detoxication group to those of
      the metoprolol group (P < 0.05). Compared with the sham-operation group, the
      serum TNF-alpha level and myocardial TNF-alpha mRNA expression were significantly
      increased in the model group (P < 0.05, P < 0.01). Compared with the model group,
      not only the serum TNF-alpha level was significantly decreased, but also the TNF
      alpha gene expression in the myocardial tissue was improved in the activating
      blood circulation and detoxication group (P < 0.01). CONCLUSION: Combined use of
      activating blood circulation and detoxication drugs could play an effective role
      in treatment of coronary heart disease by fighting against platelet activation,
      improving the hypercoagulable state, and inhibiting inflammation, which was
      significantly better than using activating blood circulation and removing stasis
      drugs alone.

PMID- 25566625
TI  - [Effect of pungent dispersion bitter purgation method on the esophageal mucosal
      intercellular space of reflux esophagitis model rats].
AB  - OBJECTIVE: To observe the effect of pungent dispersion bitter purgation method
      (PDBPM) on the esophageal mucosal intercellular space of reflux esophagitis (RE)
      model rats. METHODS: Totally 100 Wistar rats were randomly divided into the
      control group, the model group, the Western medicine group (WM), the Chinese
      medicine group (CM), 25 rats in each group. Rats in the control group only
      received switch operation. Rats in the rest three groups received modified
      partial cardia muscle incision combined pylorus ligation of external parts to
      prepare the RE rat model. Starting from the 3rd day after operation, WM mixture
      (Motilium 3. 2 mg/kg + Omeprazole Capsule 4.3 mg/kg + Hydrotalcite Tablet 161.4
      mg/kg) was administered by gastrogavage to rats in the WM group. Rats in the CM
      group was administered by gastrogavage with Modified Banxia Xiexin Decoction (5.7
      g/kg), 2.5 mL each time, twice daily for 14 consecutive days. Equal volume of
      normal saline was administered by gastrogavage to rats in the control group and
      the model group. On day 7 and 14, the lower esophagus pH value, general specimen
      of mucosa and histopathologic changes were observed. Intercellular spaces of
      esophageal epithelium were measured for a control study. RESULTS: Compared with
      the same group at day 7, the lower esophagus pH value increased at day 14 (P <
      0.01); the naked eye integral of esophageal mucosa and intercellular spaces of
      esophageal epithelium also decreased at day 14 in the CM group and the WM group
      (P < 0.05). Compared with the control group at the same time point, the lower
      esophagus pH value decreased in the model group (P < 0.01). The naked eye
      integral of esophageal mucosa, and intercellular spaces of esophageal epithelium
      increased in the model group with increased intercellular spaces (P < 0.01).
      Compared with the model group at the same time point, the lower esophagus pH
      value increased and the naked eye integral of esophageal mucosa decreased in the
      CM group and the WM group at day 7 and 14 (P < 0.01). Intercellular spaces of
      esophageal epithelium of RE model rats at day 14 was lower in the CM group and
      the WM group than in the model group (P < 0.01). Compared with the WM group, the
      lower esophagus pH value decreased at day 7 in the CM group (P < 0.05); the naked
      eye integral of esophageal mucosa and intercellular spaces of esophageal
      epithelium decreased at day 14 in the CM group (P < 0.05). CONCLUSIONS: PDBPM had
      favorable treatment effect on RE model rats. The therapeutic effect was more
      obvious along with the therapeutic course went by. Its mechanism might be
      achieved through good repair effect on damaged mucosa, increasing the pressure of
      esophageal sphincter, and inhibiting gastric acid.

PMID- 25566626
TI  - [Effect of heche chongcao capsule on expression of TNF-alpha protein in rats with
      chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To observe the expression of tumor necrosis factor-alpha (TNF-alpha)
      protein in the lung tissue of rats with chronic obstructive pulmonary disease
      (COPD), and to evaluate the intervention and mechanism of Heche Chongcao Capsule
      (HCC). METHODS: The COPD rat model was prepared by exposure to cigarettes smoke
      plus intratracheal injecting lipopolysaccharide (LPS). Forty successfully modeled
      SD rats were randomly divided into the COPD model group, the control group, the
      low dose HCC group, the medium dose HCC group, and the high dose HCC group, 8 in
      each group. Meanwhile, a normal control group consisting of 6 rats was also set
      up. HCC at 0.25, 0.5, and 1.0 g/kg was administered to rats in the 3 dose HCC
      groups respectively by gastrogavage combined with Theophylline Sustained Release
      Tablet (TSRT). Rats in the control group were administered with TSRT by
      gastrogavage at 4.5 mg/kg, 1 mL/100 g each time, once daily. All medication
      lasted for 4 successive weeks. Equal volume of distilled water was administered
      by gastrogavage to rats in the COPD model group and the normal control group.
      Morphological changes of the lung tissue were observed under microscope. The
      expression of TNF-alpha protein in the lung tissue were also detected using Real
      time PCR. RESULTS: Under electron microscope, the cilium in the tracheal
      epithelium was disorderly arranged, type I and II alveolar cells were
      degenerated, endoplasmic reticulum and mitochondria were swollen, the lamellar
      body was emptied, and free fragment could be seen inside alveolar space. Compared
      with the model group, all lesions were somewhat ameliorated in all medicated
      groups, especially in the medium dose HCC group. Compared with the model group,
      the expression of TNF-alpha protein decreased in all medicated groups, especially
      in the medium and low dose HCC groups (P < 0.05, P < 0.01). Compared with the
      control group, the expression of TNF-alpha protein decreased in the medium and
      low dose HCC groups (P < 0.05). CONCLUSION: HCC could effectively regulate the
      expression of TNF-alpha protein and inhibit airway inflammation reaction in COPD
      rats.

PMID- 25566627
TI  - [Reversal Effect of curcuma wenyujin extract on SGC-7901/VCR induced subcutaneous
      transplanted tumor in nude mice and its effect on the expression of P
      glycoprotein].
AB  - OBJECTIVE: To explore the reversal effect of multidrug resistance of Curcuma
      Wenyujin (CW) and its possible mechanism by establishing Vincristine-resistant
      gastric cancer SGC-7901 cells (SGC-7901/VCR) induced subcutaneous transplanted
      tumor in nude mice. METHODS: First we identified the resistance of SGC-7901/VCR
      by using methyl thiazolyl tetrazolium (MTT). The SGC-7901/VCR induced
      subcutaneous transplanted tumor model was established in 50 BALB/c nude mice by
      tissue block method. After 2 -3 weeks 36 mice with similar tumor size were
      selected and divided into 6 groups by random digit table, i.e., the model group,
      the Vincristine (VCR) group, the low dose CW group, the high dose CW group, the
      low dose CW combined VCR group, and the high dose CW combined VCR group, 6 in
      each group. Normal saline was intraperitoneally injected to mice in the model
      group at 10 mL/kg, once per 2 days. VCR was intraperitoneally injected to mice in
      the VCR group at 0.28 mg/kg once per 2 days. CW at 1.4 and 2.8 g/kg was
      administered to mice in the low and high dose CW groups by gastrogavage, 0.2 mL
      each time, once daily. CW at 1.4 and 2.8 g/kg was administered by gastrogavage
      and VCR was intraperitoneally injected at 0.28 mg/kg, once per 2 days to mice in
      the low dose CW combined VCR group and the high dose CW combined VCR group. All
      medication lasted for 14 days. The tumor growth was observed. The inhibition rate
      was calculated. Meanwhile, the positioning and expression of P-glycoprotein (P
      gp) were detected by immunohistochemistry and Western blot. RESULTS: SGC-7901/VCR
      had strong resistance to VCR, Adramycin (ADM), fluorouracil (5-FU), and Cisplatin
      (DDP), especially to VCR. Proliferation activities of SGC-7901/VCR were
      significantly enhanced after drug elution. The tumor volume gradually increased
      as time went by. The tumor volume was the minimum in the high dose CW combined
      VCR group. The tumor volume was obviously reduced in the high dose CW combined
      VCR group with obviously reduced with increased inhibition rate of 51.56%, when
      compared with that of the model group and the VCR group (P < 0.05). Western blot
      test showed that, when compared with the model group, the gray level of P-gp in
      the VCR group increased (P < 0.05), and the relative expression of P-gp in the
      high dose CW group, the low dose CW combined VCR group, and the high dose CW
      combined VCR group significantly decreased (P < 0.05). Compared with the VCR
      group, the gray level of the P-gp decreased in the low dose CW group, the high
      dose CW group, the low dose CW combined VCR group, and the high dose CW combined
      VCR group (P < 0.05). Results of immunohistochemistry showed that, when compared
      with the model group, expression scores of P-gp in the high dose CW group, the
      low dose CW combined VCR group, and the high dose CW combined VCR group decreased
      with statistical difference (P < 0.05). Compared with the VCR group, expression
      scores of P-gp were obviously lowered in the low dose CW group, the high dose CW
      group, the low dose CW combined VCR group, and the high dose CW combined VCR
      group (P < 0.05). CONCLUSIONS: CW could reverse the drug resistance of SGC
      7901/VCR subcutaneous transplanted tumor. And its mechanism might be related to
      down-regulating the expression of P-gp, suggesting that CW could be used as a
      kind of multidrug resistance reversal agent based on P-gp.

PMID- 25566628
TI  - [Effect of extract of radix tetrastigma hemsleyani on apoptosis of human lung
      carcinoma H1299 cells and its mechanism study].
AB  - OBJECTIVE: To study the effect of extract of Radix Tetrastigma hemsleyani on the
      proliferation and apoptosis of human lung carcinoma H1299 cells, and to explore
      its mechanisms. METHODS H1299 cells were treated with the extract of Radix
      Tetrastigma hemsleyani in different concentrations at different time points. Its
      inhibition on H1299 cell proliferation was detected by Cell Counting Kit-8 (CCK
      8) assay. The morphology of the H1299 cell was observed by inverted microscope.
      Changes of apoptosis were observed by Hoechst33258 methods. The apoptosis rate
      was detected by flow cytometry. Expression changes of apoptosis-related proteins
      pro-caspase-3, pro-caspase-9, cle-caspase-3, cle-caspase-9, and poly-ADP-ribose
      polymerase (PARP) were detected by Western blot. RESULTS: Compared with the
      control group, the inhibition rate of H1299 cells increased after acted by 0.5,
      1, 5, and 10 mg/mL extract of Radix Tetrastigma hemsleyani (P < 0.05, P < 0.01).
      The longer the acting time, the higher the inhibition rate (P < 0.01). Under
      inverted microscope, typical morphological changes could be seen and the number
      of H1299 cells was reduced. Under fluorescence microscope, dark stained nucleus
      and formed apoptotic body could be observed. Results of flow cytometry showed
      that the apoptosis rate was obviously dose-effect correlated with the
      concentration of extract of Radix Tetrastigma hemsleyani. Results of Western blot
      indicated that compared with the control. group, the protein expression of pro
      caspase-3, pro-caspase-9, and PARP were down-regulated and that of cle-caspase-3,
      cle-caspase-9, and cle-PARP were up-regulated by 5 and 10 mg/mL extract of Radix
      Tetrastigma hemsleyani (P < 0.05). CONCLUSIONS: Extract of Radix Tetrastigma
      hemsleyani had obvious effect in inhibiting the proliferation and inducing
      apoptosis of human lung carcinoma H1299 cells, which might be achieved by
      activating the expression of caspase protein.

PMID- 25566629
TI  - [Effect of modified zuoguiwan on Th17/Treg subpopulation of estrogen deficiency
      induced bone loss mice].
AB  - OBJECTIVE: To observe the effect of Modified Zuoguiwan (MZ) on the balance
      between helper T cell subsets 17 (Th17) and regulatory T cell subsets (Treg) in
      estrogen deficiency induced bone loss mice and to explore its mechanism. METHODS:
      Totally 50 BALB/c mice were divided into the sham-operation group, the
      ovariectomy model group, the low dose MZ group, the middle dose MZ group, and the
      high dose MZ group by random digit table, 10 in each group. Mice in the low,
      middle, and high dose MZ groups were respectively administered with MZ at the
      daily dose of 7.25, 14.50, and 29.00 g/kg by gastrogavage, 0.5 mL each time for
      12 successive weeks. Meanwhile, mice in the sham-operation group and the
      ovariectomy model group were administered with equal volume by gastrogavage, 0.50
      mL each time. The serum estradiol (E2) level was assessed by enzyme linked
      immunosorbent assay (ELISA). Bone mineral density (BMD) of thigh bone was
      measured with dual energy X ray absorptiometry. In addition, the population of
      Th17/Treg subsets in spleen mononuclear cells was analyzed by extracellular and
      intracellular staining method using flow cytometry. Moreover, the mRNA expression
      of IL-17A and TGF-beta in the spleen mononuclear cells was detected by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: Compared with the sham
      operation group, both E2 and BMD significantly decreased, the percentage of Th17
      subset and Th17/Treg ratio both increased, the percentage of Treg subset
      obviously decreased, the expression of IL-17A mRNA significantly increased, and
      the expression of TGF-beta mRNA significantly decreased in the ovariectomy model
      group (all P < 0.05). Compared with the model group, BMD obviously increased, the
      percentage of Th17 subset and Th17/Treg ratio both decreased, the percentage of
      Treg subset obviously increased, the expression of IL-17A mRNA significantly
      decreased, and the expression of TGF-beta mRNA significantly increased in the
      middle dose MZ group and the high dose MZ group (all P < 0. 05). Correlation
      analyses showed that BMD was positively related to both the serum E2 level and
      the percentage of Treg subset (P < 0.05), but negatively related to the
      percentage of Th17 subset (P < 0.05). In addition, the serum E2 level was
      positively related to the percentage of Treg subset, but obviously negatively
      related to that of Th17 subset (P < 0.05). CONCLUSIONS: There was correlation
      between Th17/Treg imbalance and E2 deficient bone loss. MZ could decrease the
      proportion of Th17 subset, but elevate the proportion of Treg subset in E2
      deficient bone loss mice. It could achieve therapeutic effect through adjusting
      the balance of Th17/Treg in E2 deficient bone loss mice.

PMID- 25566630
TI  - [Effect of 5 warm-hot nature Chinese drugs for promoting blood circulation and
      removing blood stasis on 5-HT, NE, and endocrine hormones of rats of cold
      coagulation and blood stasis syndrome].
AB  - OBJECTIVE: To study the mechanism of warm-hot nature Chinese drugs (WHNCD) for
      promoting blood circulation and removing blood stasis (PBCRBS) for intervening
      model rats of cold coagulation and blood stasis syndrome (CCBSS). METHODS: CCBSS
      rat model was set up in outbred SD rats using ice water immersion method. Totally
      300 successfully modeled CCBSS rats were randomly divided into 5 groups according
      to the principle of balance weight, 60 in each group. Contents of triothyrone
      (T3), tetraiodothyroine (T4), progesterone (P), 5-hydroxytryptamine (5-HT), and
      noradrenalin (NE) were paralleledly detected in all groups. Then rats in each
      group were subdivided into 6 subgroups as the model group, the curcuma group, the
      Ligsticum Chuanxiong group, the safflower group, the Rhizoma Corydalis group, and
      the Olibanumg group. Besides, 5 normal control groups were set up for 5 indices,
      50 rats in total. We need 70 rats (7 groups) to finish observing 1 index, 350
      rats in total for 5 indices. Except those in the model group and the normal
      control group, rats were administered with corresponding decoction at 20 g crude
      drugs/kg body weight by gastrogavage, 3 mL each time, once daily for 7 successive
      days. Equal volume of normal saline was given to rats in the normal control group
      and the model group. Contents of T3, T4, P, 5-HT, and NE were detected before
      treatment and 1 week after treatment. RESULTS: Compared with before treatment in
      the same group, T3 increased in the Ligsticum Chuanxiong group and the Olibanumg
      group, 5-HT increased in the Ligsticum Chuanxiong group, T4, NE, and P increased
      in all medicated groups (P < 0.05). Compared with the normal control group,
      contents of T3, T4, 5-HT, NE, and P in the model group decreased (P < 0.05).
      Compared with the model group, contents of T3, T4, 5-HT, and NE increased in each
      medicated group (P < 0.05). There was statistical difference in contents of P
      between the Ligsticum Chuanxiong group and the Olibanumg group (P < 0.05).
      CONCLUSIONS: WHNCD for PBCRBS had regulatory roles in serum contents of T3, T4,
      P, and NE in modeled rats of CCBSS. They could promote the thyroid gland-gonadal
      axis function, enhance the function of the endocrine system, which might be one
      of the pharmacodynamic mechanism of WHNCD for PBCRBS in intervening CCBSS.

PMID- 25566631
TI  - [Experimental study on anti-tumor effect and mechanism of green tea extract].
AB  - OBJECTIVE: To explore anti-cancer effect and mechanism of green tea extract (GTE)
      in three human oral squamous carcinoma cell lines (CAL-27, SCC-25 and KB).
      METHODS: The cell lines were in vitro cultured and its growth inhibition was
      detected by MTT. After screening most sensitive cell line, effect of GTE on CAL
      27 cell cycle was analyzed by flow cytometry. The protein expression of GTE on
      CAL-27 cell strain was determined by protein chip technique. The protein
      expression of CDK4, CDK6, and p-PDK1 was verified by using Western blot. RESULTS:
      Compared with the control group, the inhibition rate on CAL-27 increased
      significantly after treated by 50, 100, 200, and 400 MUg/mL GTE; the inhibition
      rate on KB increased after treated by 100, 200, and 400 MUg/mL GTE; the
      inhibition rate on SCC-25 increased after treated by 25, 50, 100, 200, and 400
      MUg/mL GTE, all with statistical difference and in dose dependant manner (P <
      0.01). Flow cytometric analysis showed that, when compared with the control
      group, 50 MUg/mL GTE arrested CAL-27 cells in the G2/M phase (P < 0.05), and 100
      MUg/mL GTE arrested CAL-27 cells in the G2/M phase with concurrent decreased
      cells in the G0/G1 phase (P < 0.01). Totally 107 proteins were analyzed by
      protein chip technique. After treated by GTE, a total of 13 proteins
      significantly changed in CAL-27 cell line. Western blot showed that 25, 50, and
      100 MUg/mL GTE inhibited the expression of phopho-phosphoinositide-dependent
      protein kinase 1 (p-PDK1), cyclin-dependent kinase 4 (CDK4), and CDK6 of CAL-27
      cell line with statistical difference (P < 0.05). The higher the drug
      concentration, the higher the inhibition rate (P < 0.05). CONCLUSIONS: GTE could
      inhibit the proliferation of different human oral squamous carcinoma cell lines.
      CAL-27 is a sensitive cell line. GTE significantly affected EGFR and Notch signal
      network, and influenced changes of cell cycle related protein expression levels
      through the aforesaid channels, resulting in cell cycle arrest in S and G2/M
      phases.

PMID- 25566632
TI  - [Bilateral regulation of luteolin on spleen cells and sarcoma S180 cells of ICR
      mice: an experimental study].
AB  - OBJECTIVE: To study the regulation of luteolin on spleen cells and sarcoma S180
      cells in normal ICR mice. METHODS: Spleen cells and S180 cells were incubated
      with different concentrations of luteolin (50, 100, 200, and 400 MUmol/L). The
      effect of luteolin on spleen cells and sarcoma S180 cells was determined by MTT
      assay. The apoptosis was detected using propidium iodide staining flow cytometry.
      Intracellular reactive oxygen species (ROS) was determined by flow cytometric
      analysis. Activities of free radicals scavenging were determined by hydroxyl
      radical and DPPH tests. RESULTS: Compared with the solvent control group, 200 and
      400 MUmol/L luteolin increased the spleen cells viability (P < 0.05). Luteolin at
      100, 200, and 400 MUmol/L decreased activities of S180 cells (P < 0.01). The
      proportion of sub-G1 phase spleen cells was reduced after treated with 200 and
      400 MUmol/L luteolin (P < 0.05). The proportion of sub-G1 phase S180 cells was
      elevated after treated with 200 and 400 MUmol/L luteolin (P < 0.05). Compared
      with the solvent control group, levels of intracellular ROS in spleen cells of
      ICR mice all increased; levels of intracellular ROS in S180 cells all decreased
      after treated with 50, 100, 200, and 400 MUmol/L luteolin (P < 0.05). Luteolin
      scavenged hydroxyl radical and DPPH in a dose dependent manner. CONCLUSION:
      Luteolin had bilateral regulation on viability and apoptosis of spleen cells and
      S180 cells (promoting the viability of spleen cells, inhibiting apoptosis of
      spleen cells, inhibiting the viability of S180 cells, and promoting apoptosis of
      S180 cells), which was worth further study and exploration.

PMID- 25566633
TI  - [The application of blood stasis theory in clinical treatment of skin disease].
AB  - Blood stasis theory (BST) is widely used in the department of Chinese medical
      dermatology. Skin lesion we often see and modern medical examination results can
      be used as evidence for diagnosing BST and indications for using it. Better
      efficacy could also be obtained by using BST in treating wind evil or heat evil
      induced skin disease, and itching, hemorrhagic and stubborn dermatoses as well.

PMID- 25566634
TI  - [Scientific connotation of Chinese medicine refracted in bioenergetics].
AB  - The discovery of the electron leak pathways of mitochondrial respiratory chain
      reveals that the respiratory chain not only included in ATP synthesis through the
      electron transfer pathway but also included in reactive oxygen species (ROS)
      generation through the electron leak pathways. The negative effect of ROS is the
      reason for causing pathological event, but more important is the signaling role
      of ROS, which had important physiological effect. In this article we take the
      human body as an aggregate of a huge amount of life-engine and perceive the
      respiratory chain as "yin-yang" element to describe the modern life science
      connotation born in the "yin-yang" theory of Chinese medicine.

PMID- 25566635
TI  - [An establishment of theoretical structure of PRO questionnaire in treating
      chronic liver disease by Chinese medicine].
AB  - By reviewing research contents of patient-reported outcome (PRO) and discussing
      Chinese medicine (CM) theories related to chronic liver disease (CLD), we have
      followed international PRO questionnaire development specification, combined CM
      theories such as uniformed spirit and body, correspondence between human and the
      universe, yin in property and yang in function of Gan, and seven emotions, and
      constructed theoretical structure of PRO questionnaire of treating CLD, including
      four major areas as physiology, psychology, independence, and society and nature.
      Of them, the physiological field contained six aspects such as blood deficiency,
      yin deficiency, bleeding, disorder of qi movement, improper transformation and
      transportation of Pi-Wei, and abnormal biliary excretion. The psychological field
      contained two aspects: Gan-related emotions and general disease related emotions.
      The independence field contained two aspects: daily life and study and work. The
      field of society and nature contains three aspects: social relations, social
      environment, and natural adaptability.

PMID- 25566636
TI  - [Preliminary clinical experience of Prof. Li Pei-wen in treating complications of
      tumor by external treatment of traditional Chinese medicine].

PMID- 25566637
TI  - [Treatment of Castleman disease by Chinese medical syndrome typing: a case
      report].

PMID- 25566638
TI  - [Research progress on mechanism of activating blood circulation to remove stasis
      treatment for diabetic angiopathy].

PMID- 25566639
TI  - [Research progress on mechanism for diabetic perineuropathy and its invention by
      compound jinmaitong capsule].

PMID- 25566641
TI  - [Study on cutting and gemmae propagation of Huperzia serrata].
AB  - OBJECTIVE: An efficient and stable artificial propagation system of Huperzia
      serrata was established by developing the wild semi-assisted reproductive system
      with gemmae or the cutting of stem tip. METHODS: The study was explored in the
      forest farm of Yantuozhai, Gaowangjie,Guzhang County, Xiangxi state and designed
      as a L9 (3(4)) orthogonal experiment, which consisted of three factors including
      cutting length, NAA concentration and soak time, to research their effect on
      rooting of perennial branches attached tip. The experiment also investigated the
      gemmae's occurrence, distribution and growth development through wild observation
      of two years and the gemmae germination of placed in different soil layers were
      studied. RESULTS: In the original habitat, the best treatment was the cutting of
      6 cm length with NAA 20 mg/L immersing for 5 min. The white adventitious root
      occurred 60 d later whose survival rated up to 90%. The cutting growth increased
      distinctly after 210 d. The gemmaes developed in July to September every year,
      matured in March to April next year. After separated from the mother plants, the
      gemmaes could germinate and grow as seedlings when the condition was suitable.
      Germination experiments showed that light and humidity were the main factors
      affecting gemmae germination. CONCLUSION: It is feasible to establish the cutting
      propagation of Huperzia serrata in natural habitat. An efficient and stable
      regeneration system was developed with gemmae's artificial germination. This
      study is of great significance to alleviate the meager resources of Huperzia
      serrata.

PMID- 25566640
TI  - [Research progress on synergistic effect of needling in treating myocardial
      ischemia combined with tanshinon II A].

PMID- 25566642
TI  - [Tissue cultivation of Lonicera macranthoides 'Yuleil'].
AB  - OBJECTIVE: To establish the rapid tissue propagation system of Lonicera
      macranthoides 'Yuleil ', in order to provide theoretical basis for industrialized
      seed cultivation. METHODS: Young stem and leaves of Lonicera macranthoides
      'Yuleil' were used as explants, with MS as basic media, and added with different
      concentrations of plant growth regulators such as NAA, 6-BA, TDZ and IBA in
      different stages of tissue culture, in order to conduct a systematic study on
      callus induction, proliferation and differentiation, and stem axillary bud
      induction, proliferation, rooting and seedlings. RESULTS: Best sterilization time
      of explant was:stem for 2 - 3 min, leaves for 1 - 2 min. The optimal medium for
      callus induction was MS + 2,4-D 1.0 mg/L + 6-BA 0.1 mg/L. The optimal medium for
      axillary bud induction, callus proliferation, callus differentiation, bud
      proliferation and rooting was MS + 6-BA 1.0 mg/L + NAA 0.5 mg/L, MS + TDZ (0.2 -
      1.0) mg/L + NAA (0.02 - 0.05) mg/L, MS + 6-BA (0.5 - 1.0) mg/L + NAA (0.02 -
      0.05) mg/L, MS + 6-BA 1.5 mg/L + NAA 0.5 mg/L and 1/2MS + IBA 1.0 mg/L + NAA 0.2
      mg/L, respectively. Tube seedlings was refined in matrix include pearlite and
      humus (1: 1), with the survival rate of more than 75%. CONCLUSION: The
      disinfection method suitable for explants and the medium combination suitable for
      callus induction, proliferation, differentiation as well as bud proliferation and
      rooting are screened out to establish the rapid cultivation system for Lonicera
      macranthoides 'Yuleil'.

PMID- 25566643
TI  - [Study on seeds after-ripening regulation and key techniques for seedling of
      Pulsatilla cernua].
AB  - OBJECTIVE: The seeds of Pulsatilla cernua were used as tested materials for
      screening and establishing the main factors with different levels to control fast
      development of seed embryonic and seedlings of Pulsatilla cernua. METHODS: The
      main factors with different levels for development of seed embryonic and
      seedlings of Pulsatilla cernua were investigated through repeated experiments
      with multifactorial and cross. RESULTS: The method for development of seedlings
      and seeds germination of Pulsatilla cernua were to soak the seeds in the mixed
      solutions with 2.40 mg/L KT, 2.80 mg/L GA3 and 0.30 -0.70 mg/L 2,4-D for 24 h.
      The seeds and sand (1:2) were mixed, treated with temperature change in 63 - 70
      d. The extent of temperature change and time were (23 +/- 2) degrees C and 14 h
      in day, while (10 +/- 2) degrees C and 10 h in night. The incidence rate of the
      embryo with cotyledons was 95.1%, and the germination rate of seed was 92.3%.
      CONCLUSION: The plant regeneration control technology for development of seed
      embryonic and seedling of Pulsatilla cernua have been solved, which is suitable
      for industrial seedlings of Pulsatilla cernua.

PMID- 25566644
TI  - [Accumulation dynamic of triterpenoid saponins in Akebia trifoliata stem].
AB  - OBJECTIVE: In order to understand the accumulation dynamic of triterpenoid
      saponins in Akebia trifoliata stem to determine the suitable harvesting time and
      the growth age of stem. METHODS: The contents of effective components, oleanolic
      acid and hederagenin in Akebia trifoliata stems, collected at the same growth
      condition of different growth ages and different harvesting time, were compared
      by high performance liquid chromatography (HPLC). RESULTS: The accumulation
      period of oleanolic acid was from the first year to the sixth year, the content
      rose quickly in the seventh year, and reached the greatest at the ninth year,
      then declined quickly, the contents in stem of more than 10 years had no
      significant difference compared with that of 1 - 6 years. The content of
      herderagenin had no great change by the age of stem. CONCLUSION: Comprehensive
      consideration,the triterpenoid saponins contents of the eight to nine years old
      Akebia trifoliata stems were higher. The most appropriate harvesting time for
      Akebia trifoliata was from later August to later September in the eighth years.

PMID- 25566645
TI  - Isolation and purification of two antioxidant peptides from alcalase hydrolysate
      of Arca subcrenata.
AB  - OBJECTIVE: To investigate the constituents with antioxidant activities from
      alcalase hydrolysate of Arca subcrenata. METHODS: The consecutive chromatographic
      methods were employed,including ion-exchange chromatography, gel filtration
      chromatography, and reverse phase high-performance liquid chromatography (RP
      HPLC). The amino acid sequences of the purified antioxidant peptides were
      determined by automated Edman degradation. RESULTS: Under the guidance of the
      assay of scavenging free radicals, two peptides with antioxidant activities,
      termed as A-Bg1 and A-Bh, were isolated and purified from the alcalase
      hydrolysate of Arca subcrenata. CONCLUSION: Constituents from the hydrolysate of
      Arca subcrenata might be a new potential resource of antioxidants.

PMID- 25566646
TI  - [Determination of chlorogenic acid and luteoloside in lonicerae flos of different
      habitats and germplasms].
AB  - OBJECTIVE: To establish an UPLC-PDA method for simultaneous determination of
      chlorogenic acid and luteoloside in Lonicerae Flos. On the basis of developed
      method, the quality of Lonicerae Flos from nine habitats and two local germplasms
      introduced from Qufu in Shandong to Wuming in Guangxi was evaluated. METHODS: The
      analysis was performed on a Waters Acquity UPLC H-Class system. An Acquity UPLC
      BEH RP18 (100 mm x 2.1 mm,1.7 MUm) column was used for all analyses. The
      investigated compounds were separated with a gradient mobile phase consisting of
      acetonitrile and 0.4% phosphoric acid solution at a flow rate of 0.2 mL/min, and
      the detection wavelength was set at 242 nm. RESULTS: The quality of Lonicerae
      Flos from Qufu was the best among Lonicerae Flos of nine habitats for its content
      of chlorogenic acid and luteoloside at 35.715 and 1.270 mg/g, respectively. The
      content of chlorogenic acid and luteoloside in Lonicerae Flos of "Jiufengyihao"
      and "Shuxing" introduced from Qufu to Wuming both complied with the standard of
      Chinese Pharmacopoeia (2010 edition). CONCLUSION: The developed UPLC-PDA method
      is simple, reliable and repeatable, which is helpful for the quality control of
      Lonicerae Flos. "Jiufengyihao" and "Shuxing" are potential germplasms for the
      introduction of Lonicerae Flos in Wuming.

PMID- 25566647
TI  - [Determination of quercetin and kaempferol in Fagopyrum spp. of different species
      and different parts by HPLC].
AB  - OBJECTIVE: An HPLC method was established for determination of quercetin and
      kaempferol in Fagopyrum spp. of differrent species and different plant parts.
      METHODS: The chromatographic separation was carried out on a DIKMA diamonsil (250
      mm x 4.6 mm, 5 MUm) chromatographic column. The mobile phase was acetonitrile (A)
      and 0.1% phosphoric acid solution (B) at the flow rate of 1.0 mL/min. The
      detection wavelength was set at 260 nm and the column temperature was 25 degrees
      C. RESULTS: The descending order of quercetin content in the samples of different
      parts of Fagopyrum tataricum was seed (6.12 mg/g) > leaf (1.47 mg/g) > stem (0.34
      mg/g); quercetin was not found in root. Only a few kaempferol was found in seed
      (0.42 mg/g) and leaf of Xiqiao 1 (0.09 mg/g) of Fagopyrum tataricum. There were a
      few quercetin was determined in the whole plant of Fagopyrum esculentum, and
      kaempferol was not been found. The total and mean value concentration of
      quercetin and kaempferol of Fagopyrum tataricum were much higher than that of
      Fagopyrum esculentum. In different species of Fagopyrum tataricum planted in the
      same area, the content of quercetin and kaempferol was similar, they were not
      been found in Fagopyrum esculentum. CONCLUSION: This method is simple, rapid,
      accurate and reliable for quality evaluation of Fagopyrum spp. and its commercial
      products.

PMID- 25566648
TI  - [Analysis of dynamic changes of flavonoids and alkaloids during different drying
      process of Morus alba leaves].
AB  - OBJECTIVE: To find out dynamic changes of flavonoids and alkaloids in Morus alba
      leaves by analyzing influence of different drying method and drying degrees, in
      order to provide evidence for quality evaluation of Morus alba leaves. METHODS:
      Different drying methods, programmed temperature methods and constant temperature
      methods were adopted to dry Morus alba leaves samples respectively. Contents of
      flavonoids and alkaloids were analyzed by HPLC-PDA and LC-TQ/MS respectively.
      RESULTS: It's shown obviously that the content of flavonoids were influenced
      heavily by different drying methods. Methods that suitable for flavonoids were
      freezing-dried > shade-dried > dried > sun-dried > microwave-dried > infrared
      dried; Methods that suitable for alkaloids were freezing-dried > shade-dried >
      dried > sun-dried > infrared-dried > microwave-dried. The 55 -65 degrees C group
      was shown to be the lowest in both flavonoids and DNJ while the 85 - 95 degrees C
      group was shown to be the best for DNJ. For fagomine, the 45 degrees C group was
      shown to be the lowest concentrations while the 95 - 105 degrees C group was
      shown to be the highest. Samples with different moisture were shown to be
      different in content of flavonoids and alkaloids. And samples with 10% moisture
      contain highest flavonoids while those with 30% - 50% moisture contain lowest
      flavonoids. Content of DNJ and fagomine raised as moisture decreasing. In
      addition, the 55 - 65 degrees C group was better than the 95 -105 degrees C one
      in alkaloids content. CONCLUSION: The results provide optimal drying methods and
      condition for drying Morus alba leaves, and foundations for uncovering
      biochemical transform of Morus alba leaves.

PMID- 25566649
TI  - [Study on modern processing technologies of aconiti kusnezoffii radix].
AB  - OBJECTIVE: To compare different processing technologies of Aconiti Kusnezoffii
      Radix, and to optimize a kind of "low toxicity and high efficiency", simple and
      practical processing technology for Aconiti Kusnezoffii Radix. METHODS: HPLC
      method was used to determine the content of six kinds of alkaloids, and titration
      method to determine the content of total alkaloids. These contents combined with
      production were used to evaluate the modern processing technologies of Aconiti
      Kusnezoffii Radix. RESULTS: There was serious drain of Aconitum alkaloids after
      treated by soaking, and the loss rates of the content of monoester alkaloids,
      diester alkaloids and total alkaloid were 20.97%, 31.13% and 14.57%,
      respectively. The content of alkaloids could maximize the retention using wetting
      method, the best methods for reducing poison were atmospheric pressure and high
      pressure steaming cooking methods, and its total diester alkaloids content was
      too low to be detected, the contents of alkaloids in samples of two kinds of high
      temperature baking were 0.6903 mg/g and 0.5575 mg/g, which were higher than the
      requirement of Chinese Pharmacopoeia. The content of monoester alkaloids was
      0.6336 - 2.2721 mg/g of 10 kinds of processing technologies, between which there
      were nine kinds of processing technologies beyong the Chinese Pharmacopoeia
      requirement of 0.7 mg/g, while the total alkaloids content was 7.8019 - 11.2078
      mg/g. CONCLUSION: The best method for reducing poison is high-pressure steaming,
      whose content of diester alkaloids can reach the Chinese Pharmacopoeia
      requirement after treatment of wet autoclaved products, with higher content of
      total alkaloids. It is simple, controllable, and suitable for processing of
      Aconiti Kusnezoffii Radix.

PMID- 25566650
TI  - [Rapid identification for fruit drugs of rosaceae based on electrochemical
      oscillation reaction].
AB  - OBJECTIVE: To establish a rapid identification method for fruit drugs of
      Rosaceae, according to the influence of Chinese traditional medicine on the
      electrochemical oscillation reaction. METHODS: The experiments were carried out
      in H2SO4-Ce (SO4)2-CH2 (COOH)2-KBrO3 electrochemical oscillation system. The
      graphs and characteristic parameters which were formed by the disturbance of
      Rosaceous fruit drugs to the electrochemical oscillation reaction were studied.
      RESULTS: There were obvious distinction on the electrochemical fingerprints of
      five kinds of medicinal materials, and the characteristic parameters of
      oscillation life were significant different. CONCLUSION: The electrochemical
      fingerprints of five kinds of Rosaceous fruit drugs can be used to identify those
      medicinal materials. The method is simple, rapid, economic and reliable.

PMID- 25566651
TI  - [Comparison of HPLC fingerprints of Xanthium sibiricum and Xanthium mongolicum
      fruits].
AB  - OBJECTIVE: To compare and establish the HPLC fingerprint of Xanthium sibiricum
      and Xanthium mongolicum fruits for the quality control. METHODS: Sample was
      separated on C18 column (250 mm x 4.6 mm, 5 MUm) with the mobile phase consisting
      of methanol-0.2% phosphoric acid solution by gradient elution. The flow rate was
      1.0 mL/min and wavelength was set at 327 nm. RESULTS: HPLC fingerprints of
      Xanthium sibiricum and Xanthium mongolicum fruits were established, and 17 common
      peaks were found. The HPLC fingerprints of Xanthium sibiricum fruits from
      different habitats had good similarities with similaritis over 0.9, but some
      compositions' relative contents of Xanthium mongolicum fruits were different
      compared with Xanthium sibiricum. CONCLUSION: This method is accurate,
      reproducible and stable, which can be used for the quality control of Xanthium
      sibiricum fruits and distinguishing it with Xanthium mongolicum fruits
      effectively.

PMID- 25566652
TI  - [HPLC fingerprint of Calendula officinalis flower].
AB  - OBJECTIVE: To establish an HPLC fingerprint of Calendula officinalis flower for
      its quality control. METHODS: Hypersil ODS C18 column (250 mm x 4.6 mm, 5 MUm)
      was used with acetonitrile and water as mobile phase in a gradient mode at the
      flow rate of 1.0 mL/min. The detection wavelength was 220 nm and the temperature
      of column was set at 35 degrees C. The similarity was analyzed with the
      Estimating System of Similarity on the Chinese Medicine Fingerprint Chromatogram.
      RESULTS: The HPLC fingerprint of Calendula officinalis flower containing eleven
      peaks was set up. The similarity of Calendula officinalis flower from different
      habitats was greater than 0.90. CONCLUSION: This method is easy and reliable,
      which can be used to judge the habitat and control the quality of Calendula
      officinalis flower.

PMID- 25566653
TI  - [Study on chemical constituents from crop pathogenic fungus active fraction of
      Wisteria sinensis tumor].
AB  - OBJECTIVE: To study the chemical constituents from the crop pathogenic fungus
      active fraction of Wisteria sinensis tumor. METHODS: The chemical constituents
      were extracted of different concentrations and isolated by silica gel and
      Sephadex LH-20 column. The chemical structures of components were further
      elucidated by the physicochemical characters and MS, NMR spectral data. RESULTS:
      Ten compounds were isolated and identified as dibutyl phthalate (1),
      diacetonealcohol (2), pinoresinol (3), stellasterol (4), oleanolic acid (5),
      olean-12-ene-3-oxo-22,24-diol (6), betulinic acid (7), 2',4',4-hydroxy-chalcone
      (8), avicularin (9) and quercetin-3-O-beta-D-glucopyranoside (10). CONCLUSION:
      All the compounds are isolated from the genus for the first time.

PMID- 25566654
TI  - [Caffeoylquinic acid derivatives from stems of Akebia trifoliata].
AB  - OBJECTIVE: To study the chemical constituents from Akebia trifoliata stems.
      METHODS: The compounds were isolated and purified by column chromatography, and
      their structures were determined through spectroscopic techniques and
      physicochemical properties. RESULTS: Six compounds were isolated from the stems
      of Akebia trifolita and identified as cryptochlorogenic acid methyl ester (1),
      neochlorogenic acid methyl ester (2), chlorogenic acid methyl ester (3), methyl
      3,5-di-O-caffeoyl quinate (4), methyl 3,4-di-O-caffeoyl quinate (5) and methyl
      4,5-di-O-caffeoyl quinate (6). CONCLUSION: All compounds are isolated from Akebia
      genus for the first time. Compounds 1,5 and 6 demonstrate obvious inhibitory
      activities against alpha-glucosidase.

PMID- 25566655
TI  - [Study on chemical constituents from rhizome of Rabdosia flavida].
AB  - OBJECTIVE: To study the chemical constituents from the rhizome of Rabdosia
      flavida. METHODS: The compounds were isolated and purified by various
      chromatographic methods, and their structures were elucidated on the basis of
      spectral data and physicochemical properties. RESULTS: Ten compounds were
      obtained from ethyl acetate fraction of the 70% acetone extract of Rabdosia
      flavida rhizome and identified as ferruginol (1), dehydrocostuslactone (2),
      taraxasterol (3), oleic acid (4), ursolic cid (5), coniferyl aldehyde (6),
      oleanolic acid (7), 6,12, 15-trihydroxy-5, 8,11, 13-abietetra-7-one (8), 5alpha,
      8alpha-epidioxyergosta-6,22-dien-3beta-ol (9), and daucosterol (10). CONCLUSION:
      All the compounds are isolated from Rabdosia flavida for the first time.

PMID- 25566656
TI  - [Study on chemical constituents of Gardenia jasminoides(III)].
AB  - OBJECTIVE: To investigate the chemical constituents of Gardenia jasminoides
      fruits. METHODS: Various column chromatography were used in the isolation and
      purification, and physiochemical constant determination and spectral analysis
      were adopted to determine the chemical structures. RESULTS: Twelve compounds were
      isolated from Gardenia jasminoides including jasminoside I (1), gardenoside (2),
      gardaloside (3), 3-hydroxy-urs-12-ene-11-ketone(4), 5, 4'-dihydroxyl-7, 3', 5'
      trimethoxyflavone (5), 5, 7, 3', 4', 5'-pentamethoxyflavone(6), 3, 5, 6, 4'
      tetrahydroxy-3', 5'-dimethoxyflavone (7), shikimic acid (8), 1, 2, 4-benzenetriol
      (9), 3, 4-dimethoxy-benzoic acid (10), dibutyl phthalate (11) and diisobutyl
      phthalate (12). CONCLUSION: Compounds 4 - 7 and 9 -10 were isolated from this
      plant for the first time.

PMID- 25566657
TI  - [Analytical studies on flavonoids constituents in Apocynum venetom leaves by UPLC
      Q-TOF-MS].
AB  - OBJECTIVE: To establish an ultra-performance liquid chromatography quadrupole
      time-of-flight mass spectrometric (UPLC-Q-TOF-MS) method for analyzing the
      flavonoids constituents in Apocynum venetom leaves. METHODS: The analysis was
      performed on an Alltima C18 analytical column with a gradient solvent system of
      acetonitrile-1.0% acetic acid at the flow rate of 0.8 mL/min. The detection
      wavelength was at 254 nm and the column temperature was at 30 degrees C.
      Identification and detection were collected under the negative electrospray ion
      mode using Q-TOF-MS. RESULTS: 11 flavonoids constituents being separated and
      identified, six of them were detected simultaneously. The results showed that the
      six detected flavonoids constituents had good linearity between concentrations
      and peak area (r > 0.9996), and the average recoveries of the method were between
      94.3% - 103.3%. CONCLUSION: The method is accurate, reproducible, and can be used
      for the quality control of Apocynum venetom leaves.

PMID- 25566658
TI  - [Analysis on volatile components of Ficus carica fruit].
AB  - OBJECTIVE: To Analyze the volatile chemical components of Ficus carica fruits.
      METHODS: The volatile components of Ficus carica fruits were extracted by the
      three extraction methods such as SPME, SD and SE, and then analyzed by GC-MS.
      RESULTS: A total of 91 peaks were identified by GC-MS. 61 compounds came from the
      extraction methods of SPME, 7 compounds from SD, and 30 compounds from SE.
      CONCLUSION: The volatile components extracted by the three methods are not quite
      similar. Among of them, the volatile components extracted by SPME method are the
      most and have the highest resolution.

PMID- 25566659
TI  - [Ameliorated effects of cyclovirobuxine D on oxidative stress and energy
      metabolism in experimental cardiac injured rats induced by sympathetic
      overactivity in vivo].
AB  - OBJECTIVE: To investigate the ameliorated effect of CVB-D on oxidative stress and
      energy metabolism in experimental cardiac injuried rats induced by sympathetic
      overactivity in vivo. METHODS: SD rats were randomly divided into five groups as
      following: control group, model group, Vitamin E 150 mg/kg group, CVB-D low dose
      and high dose groups, respectively. The rat experimental cardiac injury model was
      established by exposed to norepinephrine (NE) 3 mg/kg by ip for 16 d. The drugs
      were administrated to rat for 16 d by ig. The body weight of rats were monitored
      during all of the experimental period. At the designing ending-time point the
      indexes were assayed as following: cardiac index, hydroxyproline,
      histopathologically examination, oxidative stress ( MDA, SOD, CAT, GSH-Px and T
      AOC) and energy metabolism indicatricle ( Na+, K(+) -ATPase, and Ca2+, Mg(2+) 
      ATPase). RESULTS: After exposed with NE for 16 d, the rats of model group was
      appeared dysfunction of oxidative stress and energy metabolism such as decreasing
      body weight, increasing cardiac index and hydroxyproline in cardiac tissue,
      decreasing Na+, K(+) -ATPase and Ca(2+), Mg(2+) -ATPase activities, and
      deteriorating the oxidative stress. Treated with CVB-D could ameliorate all of
      the exacerbated indexes. CONCLUSION: CVB-D has protective effect against
      oxidative stress and energy metabolism in rats of experimental myocardial injury
      induced by sympathetic overactivity.

PMID- 25566660
TI  - [Effect of danhong huayu oral liquid combined with insulin on prevention and
      progression of early diabetic cardiomyopathy in rats].
AB  - OBJECTIVE: To investigate effects of Danhong Huayu Koufuye (DHK), insulin and
      their combination on diabetic cardiomyopathy (DC) in streptozotocin (STZ, 50
      mg/kg, ip)-induced diabetic rats. METHODS: Rats were divided into five groups:
      normal control, diabetic treated with vehicle, insulin, DHK, and DHK plus
      insulin. The animals were treated once daily for 15 weeks starting one week after
      STZ injection. RESULTS: The combination of DHK with insulin significantly reduced
      cardiac index (P < 0.05), serum LDH (P < 0.05), AST(P < 0.05), ALT(P < 0.05) and
      HDL-C (P < 0.05) level, and promoted pancreatic and cardiac morphological changes
      as compared with the model group. CONCLUSION: It is suggested that DHK may be a
      valuable adjuvant therapy for DC.

PMID- 25566661
TI  - [Experimental study and mechanism research of 701 diedazhentonggao on acute and
      chronic soft tissue injury in rabbit].
AB  - OBJECTIVE: To study the effect and mechanism of 701 Diedazhentonggao on acute and
      chronic soft tissue injury in rabbit. METHODS: The rabbit model of acute and
      chronic soft tissue injury were established by heavy hammer blow method. The
      tissue damage scored, pain threshold value and blood rheology were detected, and
      histopathological and inflammatory cytokines in damaged tissue and gene chip were
      observed. RESULTS: 701 Diedazhentonggao significantly improved the acute soft
      tissue injury symptoms, increased the pain threshold, reduced the score values of
      local damage, improved subcutaneous ecchymosis symptoms, reduced the content of
      inflammatory cytokines in damaged tissue, repaired the injuried tissue, and
      reduced blood viscosity and the content of IL-1 and 5-HT. But the contents of IL
      6 and PGE2 in acute soft tissue injury were not reduced. The gene chip study
      expressed the drug interfered the pathway of IL-1R and white blood cell cling.
      701 Diedazhentonggao also improved the chronic soft tissue injury symptoms and
      the main performance on anti-inflammatory effect, and reduced the contents of IL
      6, IL-1 and 5-HT, but it had little effet on reducing the contents of PGE2, Fbg,
      blood and histopathological examination. CONCLUSION: 701 Diedazhentonggao has
      ameliorative effect on acute and chronic soft tissue injury, but the effect on
      acute soft tissue injuries is better than on chronic soft tissue injuries, and
      its mechanism may be related to reducing the contents of IL-1, IL-6, 5-HT and
      other related inflammatory mediators.

PMID- 25566662
TI  - [Experimental study on anti-pancreatic cancer effect of oridonin].
AB  - OBJECTIVE: To investigate the apoptotic effect of oridonin in human pancreatic
      cancer cells PANC-1, and to explore the underlying mechanism. METHODS: MTT assay
      was used to measure the cell viability. Apoptosis was determined by confocal
      laser scanning microscope after Hoechst 33342 staining and flow cytometry
      analysis after PI staining. The regulation of JNK and p38 MAPK signaling pathway
      proteins was examined by Western blot analysis. RESULTS: Treatment with oridonin
      for 24 h resulted in a marked decrease in cell viability in a dose-dependent
      manner. The IC50 value was determined as 49.80 MUmol/L for 24 h. After treatment
      with 50 micromol/L and 80 MUmol/L oridonin for 24 h, typical apoptotic nucleus
      alterations were observed with confocal laser scanning microscope and apoptotic
      rates of PANC-1 cells increased by flow cytometry analysis. Treatment with 80
      MUmol/L oridonin down-regulated protein expression of JNK, p38 and increased the
      expression of p-JNK, p-p38. Furthermore, 80 MUmol/L oridonin treatment decreased
      the expression of down-stream proteins Caspase-9, Caspase-3 and PARP in the
      apoptotic pathway as well as activated the cleavage of Caspase-9. CONCLUSION:
      Oridonin can induce apoptosis of PANC-1 cells through JNK and p38 MAPK pathway
      proteins.

PMID- 25566663
TI  - [Pharmacokinetics study of curcumin solid lipid nanoparticles by intravenous
      injection in rats].
AB  - OBJECTIVE: To study the intravenous pharmacokinetics of curcumin solid lipid
      nanoparticles in SD rats. METHODS: Rats were administrated with (iv) curcumin
      solid lipid nanoparticles and curcumin solution (8.0 mg/kg), respectively. Blood
      samples were collected and curcumin in blood plasma was determined by HPLC.
      Compartmental pharmacokinetics was analyzed by DAS software. RESULTS: After
      intravenous administration, the AUC(0-t), AUC(0-infinity) and t(1/2) of curcumin
      solid lipid nanoparticles were 1.50-fold, 1.63-fold and 4.08-fold higher than
      those of curcumin solution as (173.09 +/- 44.81) MUg x h/L vs. (114.83 +/- 13.19)
      MUg x h/L, (196.56 +/- 35.25) MUg x h/L vs. (120.66 +/- 13.95) MUg x h/L and
      (5.95 +/- 2.05) h vs. (1.46 +/- 0.03) h. CONCLUSION: The curcumin solid lipid
      nanoparticles is eliminated more slowly. The bioavailability of curcumin in rats
      increases remarkably compared with that of curcumin solution after intravenous
      administration.

PMID- 25566664
TI  - [Study on preparation of breviscapine liposomes and chemicophysical properties].
AB  - OBJECTIVE: To prepare breviscapine pro-liposomes and evaluate its properties and
      stability, as well as its interaction with the mimic-membrane. METHODS:
      Breviscapine liposomes were prepared by thin film-lyophilization method. Phase
      inversion temperature was measured by electrical conductance method and
      coalescence kinetics was studied. Water/n-octanol trans-membrane diffusion model
      was designed to study the dynamic distribution behavior between two phases,
      through the determination of diffusion rate of breviscapine and liposomes.
      RESULTS: The phase inversion temperature was 63 degrees C, the activity energy
      for coalescence was 14.66 kJ/mol. The results suggested that breviscapine from
      liposomes staying on the interface were found more than the breviscapine
      infusion. CONCLUSION: Breviscapine liposomes prepared with thin film
      lyophilization method have good physicochemical properties and stability, which
      is beneficial to treatment.

PMID- 25566665
TI  - [Optimization of process of sodium aescinate lyophilized powder].
AB  - OBJECTIVE: To determine the optimal freeze-drying process of Sodium Aescinate
      lyophilized powder in order to shorten the lyophilization cycle. METHODS: Using
      the single factor experiment and L9 (3(4)) orthogonal test to optimize parameters
      of the herbal liquid volume and concentration, pre-freezing time, pressure,
      drying time and analytical temperature. RESULTS: The best lyophilization process
      parameters were as follows: 1.0 mL herbal liquid with concentration of 10 mg/mL,
      phased cooling style, pre-freezing temperature at - 35 degrees C, 6.5 h; vacuum
      of 20 Pa;sublimation drying time of 7 h; and desorption-drying temperature of 35
      degrees C for 5.5 h. CONCLUSION: Compared with the original process conditions,
      the product quality is more stable and the freezing-drying cycle time is shorten
      of 3 h, which can provide technical reference for production process of the
      freeze-dried powder of sodium aescinate.

PMID- 25566666
TI  - [Induction of nitrosative stress in mitochondria of rats hearts in experimental
      ischemia-reperfusion of the brain and its correction by ecdysterone].
AB  - On the model of focal ischemia-reperfusion of the brain investigated the
      induction of nitrosative stress in mitochondria of rats hearts and possible
      mechanisms of protective action of ecdysterone. It is shown that focal ischemia
      reperfusion of the brain induced in myocardial mitochondria the activation of
      constitutive and inducible de novo synthesis of NO by oxidation of L-arginine and
      not oxidative synthesis of NO through the recovery of oxidized stable metabolites
      of NO. Strong evidence of induction of nitrosative stress in heart mitochondria
      by focal ischemia-reperfusion of the brain, was a significant increase in
      mitochondrial pool of nitrate- and nitrite-anions and pools of nitrosothiols,
      that is proof of the formation and decay of peroxynitrite--a key marker of
      nitrosative stress. Also was observed increase in heart mitochondria by focal
      ischemia-reperfusion of the brain, content key regulator of de novo synthesis of
      NO-hydrogen sulfide and activity of inducible arginase II and, as a result, the
      pool of carbamide, which is also a regulator of the synthesis of NO. Previous
      introduction for animals herbal extract Serratsula coronata, enriched
      ecdysterone, reduces induction nitrosative stress in mitochondria of rats hearts
      under conditions of focal ischemia-reperfusion of the brain.

PMID- 25566667
TI  - [Glycoprotein sialylation and NEU1 and ST6GAL1 expressions in erythremia].
AB  - We studied the levels of lymphocyte surface-associated sialylglycans and the
      expression of neuraminidase NEU1 and sialyltransferase ST6GAL1 genes in
      lymphocytes in erythremia patients and healthy donors as well as the levels of
      sialic acids in plasma and sialylation of alpha-acid glycoprotein and
      fibronectin. Moreover, we also investigated the type of sialic acids binding with
      its glycans using sialospecific lectins MAA and SNA. fibronectin protein in
      lymphocytes and its cell surface in erythremia disease as compared to healthy
      donors. It was shown that the levels of free sialic acids and neuraminidase
      activity in plasma are increased in erythremia disease as compared to healthy
      donors; however, MAA-II-binding activity of tested glycoproteins is decreased,
      fibronectin-1 mRNA expression in lymphocytes is increased in patients with
      erythremia. The decreasing of plasma fibronectin concentration and its heparin
      binding activity as well as increasing of lymphocyte content with surface
      associated and intracellular fibronectin were revealed in erythremia disease in
      comparison with healthy donors. Positive correlation between plasma fibronectin
      level and its heparin-binding activity and negative correlation between plasma
      fibronectin level and quantity of lymphocytes which express fibronectin inside
      the cell and on cell surface was detected. Enhanced levels of alpha2,3- and
      alpha2,6-linked residues of glycocojugates were detected on lymphocyte cell
      surface in erythremia disease using sialospecific lectins and flow cytometer as
      well as fluorescent confocal microscope. The level of NEU1 and ST6GAL1 mRNA
      expressions is significantly increased in lymphocytes in erythremia disease.
      Results of this study are clarified the mechanisms of disturbed in erythremia
      disease glycobiological processes and may therefore present new approaches for
      therapeutic opportunities.

PMID- 25566668
TI  - [Phase changes of energy metabolism during adaptation to immobilization stress].
AB  - In stress, it was showed the organ and tissue changes associated with damage by
      lipid peroxides, and the disrupted barrier function. As a consequence, it was to
      lead to a syndrome of "stress-induced lung" and violation of oxygen delivery to
      the tissues and hypoxia. Purpose of the study was to investigate the dynamics of
      changes in gas exchange, blood glucose, body temperature, oxidant and antioxidant
      system activity, as well as mitochondrial respiration by Chance under the
      influence of chronic stress (6-hour immobilization daily for 3 weeks). It was
      identified 4 phase changes of energy metabolism in the dynamics of chronic
      stress. In the first phase, hypomethabolic, instability oxidative metabolism,
      decreased oxidation of NAD-dependent substrates, significant elevation of FAD
      dependent substrates oxidation and low MRU were found. The activity of superoxide
      dismutase (MnSOD) was increased; it was occurred on a background low activity of
      glutathione peroxidase, and of misbalanced antioxidant system. After seven
      immobilizations, second phase-shift in energy metabolism, was observed, and then
      the third phase (hypermetabolic) started. It was characterized by gradual
      increase in oxidative metabolism, the restoration of oxidation of NAD-dependent
      substrates, MRU, as well as optimizing balance of oxidant and antioxidant
      systems. The fourth phase was started after 15 immobilizations, and characterized
      by the development of adaptive reactions expressed in increased tolerance of
      energy metabolism to the impact of immobilization. The results are correlated
      with changes in the dynamics of blood corticosterone. Thus, it was found the
      phase character of the energy metabolism rebuilding during the chronic stress.

PMID- 25566669
TI  - [H+-Ca2+-exchanger in the myometrium mitochondria: modulation of exogenous and
      endogenous compounds].
AB  - The properties of DeltapH-induced Ca2+-transport from isolated rat myometrium
      mitochondria was investigated. Ca2+-accu- mulation was carried out in the
      presence of Mg-ATP2- and succinate. Transport of Ca2+ recorded using Ca2+
      sensitive fluorescent probe Fluo-4 AM. It is shown that acidification of
      extramitochondrial medium is accompanied by stimulation of Ca2+ release from
      mitochondria. This process is insensitive to the tetraphenylphosphonium which is
      relatively specific Na+-Ca2+-exchanger inhibitor of mitochondrial inner membrane,
      but inhibited in the presence of monoclonal antibodies directed against the
      protein LETM1 (Anti-LETM1). LETM1 protein in some tissues is the molecular basis
      of the H+-Ca2+-exchanger functioning on mitochondria. It was found that the H+
      Ca2+-exchanger is stimulated by 100 MUM amiloride (diuretic) and inhibited by Mg
      ions in milimolar concentrations. The transport system was completely resistant
      to the action of nitric oxide (sodium nitroprusside and sodium nitrite), but was
      stimulated by macrocyclic compounds of Calixarenes (C-97 and C-99) in
      submicromolar concentrations. Thus, the mitochondria of rat myometrium probably
      not have a system of Na+-Ca2+-exchanger, and provide the maintenance of the
      matrix Ca2+-homeostasis with H+-Ca2+-exchanger. Since the transport system high
      affinity activated by Calixarenes, further investigation of the influence of
      these compounds on the transport process makes promising.

PMID- 25566670
TI  - [Mechanisms of changes of microcirculation in rats under acute
      methemoglobinemia].
AB  - It was investigated the features of microcirculation and mechanisms it's
      conditioned, under acute administration of sodium nitrite in 5 mg of dry
      substance per 100 g of body weight. It was shown that acute administration of
      sodium nitrite leads to the development of methemoglobinemia, arterial and venous
      hypoxemia, and severe tissue hypoxia. Increase in the diffusion path O2 at
      methemoglobinemia is caused due to significant hyperhydratation of lung air-blood
      barrier and its individual layers, and is accompanied by a decrease in both
      components of the diffusion capacity of the lungs for oxygen: its membrane and
      blood components. It was revealed that the administration of sodium nitrite has a
      double effect, leading to inactivation of hemoglobin, as well as to
      microcirculatory disturbances associated primarily with changes in the regulation
      of vascular tone. In this initial perfusion per unit volume of tissue per time
      unit intrinsic for the organism defines a set of mechanisms which are responsible
      for changes in tissue blood flow under methemoglobinemia.

PMID- 25566671
TI  - [Effects of N-stearoylethanolamine on the emotionality and learning ability of
      rats].
AB  - After administration of endocannabinoid-like compound N-stearoylethanolamine
      (NSE) at a dose of 0,1 and 5 mg/kg the anxiety level of rats in the elevated plus
      maze and learning ability of rats in the radial maze were investigated. It was
      revealed that NSE can change both innate and acquired behavior of rats. It was
      found that the administration of NSE decreased of anxious behavior in general,
      although number and duration of grooming were not affected. Administration of NSE
      at a dose of 5 mg/kg decreases of anxious behavior in rats but also decreases
      locomotor activity. Higher anxiolytic effect of the substance in the elevated
      plus maze and growth of learning ability in the radial maze were shown during 7
      days' introduction of NSE at a dose of 0,1 mg/kg that administration of this
      substance at a dose of 5 mg/kg. Administration of NSE at a dose of 0.1 mg/kg
      significantly reduced the total number of errors in the radial maze compared to
      the control at the first day of conditioning with food reinforcement. The latent
      period of 3rd reinforcement's taking in animals in this group was lower on the
      1st, 5th (P<0.05) and 6th (P <0.01) days. Nevertheless, it was found no
      significant differences in the behavior in rats treated with NSE in both doses
      throughout the study period. Therefore, NSE changes the behavior of rats and
      contributes to the improvement of cognitive function without negative effects
      specific to cannabinoid drugs.

PMID- 25566672
TI  - [Modulation of rat myometrium contractile activity by peptidoglycan of
      Staphylococcus aureus cell wall].
AB  - Peptidoglycan of Staphylococcus aureus cell wall impact on the both estrogen
      treated and pseudopragnant rat myometrium contractile activity dynamics was
      studied. The results of experiments shown that rat myomatrium sensitivity to
      peptidoglican depends on the hormonal background. Peptidoglycan modified the
      myometrium contractile activity of both estrogen-treated and pseudopragnant rats.
      In estrogen-treated rat myometrium peptidoglycan reduces frequency and duration
      of contractions (elongated the uterine cycle) while in the pseudopregnant rat
      myometrium it increased the amplitude as well as the duration and the freqwency
      (deshortened the uterine cycle). During the experiments we found that
      peptidoglycan has stronger uterotonic effect than prostaglandin F2alpha. In this
      connection we conclude that the changes ofmyometral contractile activity after
      peptidoglycan action may have negative effects for fertility and course of
      pregnancy.

PMID- 25566673
TI  - [The role of mitochondrial uniporter in calcium-homeostasis of the exorbital
      lacrimal gland secretory cells].
AB  - The role of mitochondrial calcium-uniporter in calcium-homeostasis maintenance
      and correlations of calcium-uniporter with other calcium-transport systems of the
      rat exorbital lacrimal gland secretory cells were studied. The experiments were
      performed on intact and digitonin-permeabilized cells. The interdependence of
      calcium-uniporter and other calcium-transporting systems functioning was
      estimated on the basis of additivity of their inhibitors/agonists effects, which
      was accompanied with a decrease in the Ca2+ content in the gland cells. It was
      found that in conditions of simultaneously inhibition of sarco endoplasmic
      reticulum Ca2+-ATPase (SERCA) and mitochondrial calcium-uniporter Ca2+ passively
      released from different calcium stores, because the effects of these calcium
      transport systems inhibitors (thapsigargin and ruthenium red, respectively) were
      additive. Similarly, the processes of inositol-1,4,5-trisphosphate receptors
      (IP3Rs) activation and calcium-uniporter inhibition were additive. In contrast,
      the effects of ryanodine and ruthenium red on the Ca2+ content in cells were
      significantly non-additive. In addition, ryanodine at concentrations 1-3 MUM
      reduced respiration rate of studied cells in dose-dependent manner, and this
      effect was persisted at cells preincubation with ruthenium red or tapsigargin.
      Thus, besides the activation of ryanodine receptors (RyRs) in endoplasmic
      reticulum, ryanodine inhibits Ca2+ influx to the mitochondrial matrix, that was
      insensitive to ruthenium red.

PMID- 25566674
TI  - [Effect of C60 fullerene on viscoelastic properties of human erythrocytes
      membrane].
AB  - The effect of C60 fullerene aqueous colloid solution (C60FAS) on viscoelastic
      properties of human erythrocytes membrane has been studied. It was established
      that the effect of C60FAS on erythrocytes depends on the medium osmolality and
      concentration of C60 fullerene in it. In particular, in isotonic solution (0,15
      mol/l NaCl) adding C60 fullerene in concentrations from 0,7 to 28 MUmol/l did not
      cause the hemolytic damage of cells. In hypotonic medium when introducing C60
      fullerene (7 MUmol/l concentration) at the beginning of erythrocyte hemolysis its
      stimulating effect was maximal and when adding C60FAS in 20 s after hemolysis
      start no this process stimulation is observed. This points to the changes in
      viscoelastic properties of erythrocyte membranes even during the first seconds of
      its interaction with C60 fullerene.

PMID- 25566675
TI  - [Dynamics of structural change of ovarian tissue under ischemia].
AB  - In this work it was investigated the dependence of the correlation of
      folliculogenesis and endocrine function of ovarian tissue on the degree of
      structural damage and oocyte volume changes during ischemia. It was shown that
      after 2 hours of ischemia at 37  degrees C the morphological transformation of
      the structural components of the ovarian tissue were reversible. In case of
      restoration of blood flow conditions by heterotopic transplantation estradiol
      level of animals was 25,9 +/- 5,18 pg/ml, progesterone--18,48 +/- 3,69 ng/ml,
      significantly higher than the castrated animals-recipients. Supplement of the
      incubation medium by the fetal bovine serum lead to decreasing by 5-7% in the
      volume of oocytes of growing follicles during in ischemia and reduced
      steroidogenic function of ovarian tissue after perfusion. Increased time of the
      ischemia up to 4 hours was founded in irreversible morphological transformation,
      reduce the volume of oocytes by 40% and the formation of sclerosed tissue after
      transplantation of the ischemic fragments of ovarian tissue.

PMID- 25566676
TI  - Experimental correction of metabolic changes in mouth at long-term hypoacidity by
      multiprobiotic "Symbiter acidophilic".
AB  - It is known, that long decrease in gastric secretion leads to the development of
      hypergastrinemia, dysbiosis and to pathological changes in digestive organs. Very
      important there is a search of ways to correction of these undesirable
      consequences. Long-term usage of omeprazole leads to metabolic disorders in
      periodontium tissues and salivary glands, such as development of NO-ergic system
      disbalance and activation of free-radical oxidation, that are positively
      corrected by multiprobiotic of new generation "Symbiter acidophilic".

PMID- 25566677
TI  - [Peculiarities of hormonal metabolic changes in adult male rats under effect of
      emotional stress induced at a time of newborn suckling].
AB  - The peculiarities of protein, lipid metabolism and sexual hormones concentration
      in adult male rats due to the impact of emotional stress in period of milk
      feeding have been studied. It has been revealed that stress in this period
      functions according to imprinting type that result in feminization of the
      parameters of sexual hormones contents and metabolic processes, which shows
      gender features in normal animals and their parameters similar to intact females.
      The concentrations of testosterone (6,78+/-0,44 nmol/l), triglycerides (2,0+/
      0,04 mmol/l), total protein (150,30+/-3,8 mg/ml) in serum of stressed males were
      similar to intact females--5,6+/-0,30 nmol/l; 2,1+/-0,1 mmol/l; 160,91+/-5,1
      mg/ml respectively. The liver concentration of testosterone (1,06+/-0,01 nmol/l),
      total protein (261,30+/-6,33 mg/ml), activity of alanineaminotransferase (1,08+/
      0,05 MUmol/hour per mg protein) of stressed male also did not differ from those
      of females indicators--1,09+/-0,05 nmol/l; 253,73+/-5,15 mg/ml; 1,05+/-0,03
      MUmol/hour per mg protein, respectively. The changes of arginine amino acid
      distribution in blood and liver as well as significant increase of nitric oxide
      level. Thus, in intact males concentration of nitric oxide in the serum was
      0,14+/-0,01 MUmol/l, in stressed males--0,61+/-0,01 MUmol/l. Thus, in adult male
      rats, due to the action of stress in the during dairy feeding, shifting the
      concent of the sex hormones, substantial violation of protein and lipid
      metabolism. Also different from physiological content of arginine amino acid,
      which are antioxidation, and increase in the concentration of nitric oxide (free
      radical), which in turn is a sign of chronic oxidative stress and damage to the
      foundation of vascular tone, which may be the initiating step in the the
      pathogenesis of male infertility.

PMID- 25566678
TI  - Thermal plasma treatment of stormwater sediments: comparison between DC non
      transferred and partially transferred arc plasma.
AB  - The disposal of enormous amount of stormwater sediments becomes an emerging
      worldwide problem. Stormwater sediments are contaminated by heavy metals,
      phosphorus, trace organic and hydrocarbons, and cannot be disposed without
      treatment. Thermal plasma decontamination technology offers a high decomposition
      rate in a wide range of toxic organic compound and immobilization of heavy metal.
      In this study, we compared the treatment results between two different modes of
      thermal plasma: (1) a non-transferred direct current (DC) mode and (2) a partial
      DC-transferred mode. The reductions of total organic carbon (TOC) were,
      respectively, 25% and 80% for non-transferred and partially transferred plasma,
      respectively. Most of the toxic organic compounds were converted majorly to CxHy.
      In the gaseous emission, the accumulated CxHy, CO, NO and H2S were significantly
      higher in partially transferred mode than in non-transferred mode. The solid
      analysis demonstrated that the concentrations of Ca and Fe were enriched by 500%
      and 40%, respectively. New chemical compositions such as KAlSi3O8, Fe3O4, NaCl
      and CaSO4 were formed after treatment in partially DC-transferred mode. The power
      inputs were 1 and 10 kW, respectively, for non-transferred DC mode and a
      partially DC-transferred mode. With a lower energy input, non-transferred plasma
      treatment can be used for decontamination of sediments with low TOC and metal
      concentration. Meanwhile, partially transferred thermal plasma with higher energy
      input is suitable for treating sediments with high TOC percentage and volatile
      metal concentration. The organic compounds are converted into valuable gaseous
      products which can be recycled as an energy source. 

PMID- 25566679
TI  - Investigating the influence of pH, temperature and agitation speed on yellow
      pigment production by Penicillium aculeatum ATCC 10409.
AB  - In this study, the combined effect of pH, temperature and agitation speed on
      yellow pigment production and mycelial growth of Penicillium aculeatum ATCC 10409
      was investigated in whey media. Different pH levels (5, 6.5 and 8), temperatures
      (25, 30 and 35 degrees C) and agitation speed levels (100 and 150 rpm) were
      tested to determine the best conditions to produce a fungal yellow pigment under
      submerged fermentation. The best production of yellow pigment (1.38 g/L) was
      obtained with a pH value of 6.5, a temperature of 30 degrees C and an agitation
      speed of 150 rpm. In contrast, the maximal biomass concentration (11.12 g/L) was
      obtained at pH value of 8, a temperature of 30 degrees C and an agitation speed
      of 100 rpm. These results demonstrated that biomass and yellow pigment production
      were not directly associated. The identification of the structure of unknown P.
      aculeatum yellow pigment was detected using UV absorption spectrum and FT-IR
      spectroscopy.

PMID- 25566680
TI  - Omalizumab for the treatment of chronic urticaria.
AB  - Urticaria is a common and often debilitating dermatological condition defined by
      the sudden appearance of wheals, angioedema or both. It is further classified
      into specific subtypes based on duration and specific triggers. Awareness and
      understanding of urticaria are important to ensure a correct initial diagnosis
      and initiate appropriate guideline-based treatment outlining a stepwise approach.
      However, in chronic urticaria, approximately 50% of patients are refractory to
      the first step, the use of licensed doses of second-generation H1-antihistamines.
      If the second step, an increase in the dose of the second-generation H1
      antihistamines, is also not successful, in the third step omalizumab (XolairTM,
      Novartis Pharma AG((c))/Genentech, Inc.((c))), an anti-IgE therapy, is
      recommended as an add-on. Of all alternative treatments mentioned in the
      guidelines, omalizumab is currently the only licensed treatment for H1
      antihistamine-refractory chronic spontaneous urticaria, has a favorable
      risk/benefit ratio and was well tolerated in clinical studies. 

PMID- 25566683
TI  - Editorial for January 2015 for JPC A/B/C.

PMID- 25566682
TI  - Alteration of immunoproteome profile of Echinococcus granulosus hydatid fluid
      with progression of cystic echinococcosis.
AB  - BACKGROUND: Cystic echinococcosis (CE), caused by Echinococcus granulosus
      metacestode, invokes a serious public health concern. Early diagnosis has great
      impacts on reduction of disability-adjusted life years. Several antigen B-related
      molecules (EgAgB; EgAgB1-5) are known to be immunopotent, but detection of EgAgB
      is variable in many patients and may not allow reliable interpretation of its
      immunological relevance. More importantly, the immunoproteome profile of hydatid
      fluid (HF) has not been addressed. METHODS: We conducted a proteome analysis of
      the HF of a single fertile cyst of CE1 and CE2 stages through two-dimensional
      electrophoresis (2-DE). Each protein spot was analyzed by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). We
      subsequently determined the immunoproteome profile employing patient sera of
      entire disease spectrum from CE1 to CE5 stages. RESULTS: We identified 40
      parasite proteins, of which EgAgB (28 spots) and antigen 5 (EgAg5; 5 molecules)
      were abundant. EgAgB proteoforms constituted the majority, mostly EgAgB1 (24
      spots), followed by EgAgB2 and EgAgB4 (2 spots each). EgAgB3 was detected only by
      liquid chromatography-MS/MS. EgAgB5 was not recognized. We also detected 38 host
      proteins, which were largely composed of serum components, antioxidant/xenobiotic
      enzymes, and enzymes involved in carbohydrate metabolism. CE1 and CE2 HF
      exhibited comparable spotting patterns, but CE2 HF harbored greater amounts of
      EgAgB and EgAg5 complexes. CE sera demonstrated complicated immune recognition
      patterns according to the disease progression; CE2 and CE3 stages exhibited
      strong antibody responses against diverse EgAgB and EgAg5 proteoforms, while CE1,
      CE4, and CE5 stages mainly reacted to EgAg5 and cathepsin B. Patient sera of
      alveolar echinococcosis (AE) cross-reacted with diverse EgAgB isoforms (36%).
      EgAg5 and cathepsin B also demonstrated cross-reactions with sera from
      neurocysticercosis and sparganosis. CONCLUSIONS: Our results demonstrated that
      detection of a single defined molecule may not properly diagnose CE, since
      specific immunodominant epitopes changed as the disease progresses.
      Immunoproteome analysis combined with imaging studies may be practical in the
      differential diagnosis of CE from AE and other cystic lesions, as well as for
      staging CE, which are pertinent to establish appropriate patient management.

PMID- 25566684
TI  - Maintenance chemotherapy in the management of epithelial ovarian cancer.
AB  - The fundamental goal of maintenance therapy of cancer is to extend a clinically
      meaningful survival endpoint (overall, symptom-free, progression-free) while at
      the same time not substantially interfering with a patient's quality of life.
      Several phase 3 randomized trials in ovarian cancer involving different anti
      neoplastics (e.g., paclitaxel, anti-angiogenic agents, olaparib) have revealed an
      improvement in progression-free survival with generally acceptable side effect
      profiles, and as a result represent in appropriately selected patients a rational
      therapeutic strategy. 

PMID- 25566681
TI  - Cardiolipin signaling mechanisms: collapse of asymmetry and oxidation.
AB  - SIGNIFICANCE: An ancient anionic phospholipid, cardiolipin (CL), ubiquitously
      present in prokaryotic and eukaryotic membranes, is essential for several
      structural and functional purposes. RECENT ADVANCES: The emerging role of CLs in
      signaling has become the focus of many studies. CRITICAL ISSUES: In this work, we
      describe two major pathways through which mitochondrial CLs may fulfill the
      signaling functions via utilization of their (i) asymmetric distribution across
      membranes and translocations, leading to the surface externalization and (ii)
      ability to undergo oxidation reactions to yield the signature products
      recognizable by the executionary machinery of cells. FUTURE DIRECTIONS: We
      present a concept that CLs and their oxidation/hydrolysis products constitute a
      rich communication language utilized by mitochondria of eukaryotic cells for
      diversified regulation of cell physiology and metabolism as well as for inter
      cellular interactions.

PMID- 25566685
TI  - The conflicting roles of tumor stroma in pancreatic cancer and their contribution
      to the failure of clinical trials: a systematic review and critical appraisal.
AB  - A nearly universal feature of pancreatic ductal adenocarcinoma (PDAC) is an
      extensive presence of activated stroma. This stroma is thought to aid in various
      tumor-promoting processes and hampers response to therapy. Here, we aim to
      evaluate the evidence that supports this role of the stroma in PDAC with
      functional experiments in relevant models, discuss the clinical trials that have
      aimed to target the stroma in this disease, and examine recent work that explains
      why these clinical trials based on stroma-targeting strategies have thus far not
      achieved the expected success. We systematically searched PubMed through August
      2014 with no restrictions to identify published peer-reviewed research articles
      assessing the effect of targeting the stroma on tumor growth or metastases in
      preclinical animal models. Five hundred and thirty articles were extracted of
      which 31 were included in the analysis. Unfortunately, due to the large variety
      in models and outcome measures, we could not perform a meta-analysis of our data.
      We find that despite an abundance of positive outcomes reported in previous
      studies on stroma targeting, a strong discrepancy exists with the outcomes of
      clinical trials and the more recent preclinical work that is in line with these
      trials. We explain the incongruities by the duration of stroma targeting and
      propose that chronic stroma targeting treatment is possibly detrimental in the
      treatment of this disease. 

PMID- 25566686
TI  - Qualitative study on needs and wishes of early-stage dementia caregivers: the
      paradox between needing and accepting help.
AB  - BACKGROUND: Early individualized interventions for informal dementia caregivers
      can prevent overburdening in the later stages. However, the needs of early-stage
      dementia caregivers (EDC) remain largely unknown. This study aimed to explore the
      needs and wishes and need for care of EDC to maximize the benefit of potential
      programs for EDC and tailor interventions accordingly. METHODS: Four focus group
      interviews with 28 informal caregivers of people with dementia (PwD) were
      analyzed using inductive content analysis. Both EDC and caregivers in the later
      stages were included to compare perceived EDC needs from different points in the
      caregiver career. RESULTS: Four themes were identified: the early-stage needs
      paradox, barriers in acceptance, facilitators in acceptance, and a transition
      from loss to adaptation. The retrospective view provided by later-stage
      caregivers differed from the view of EDC; EDC struggled with acknowledging needs
      due to fear of stigma and low acceptance. EDC stressed the importance of
      acceptance as a prerequisite for adequate adaptation, but were hindered by lack
      of knowledge, difficulty acknowledging changes, and focus on loss. In contrast,
      better understanding of the disease, increasing personal time, structuring ones
      day, and using appropriate humor can reduce negative communication, increase
      positive encounters and caregiver-confidence, contributing to positive
      interaction with the care recipient and an increase in well-being. CONCLUSIONS:
      Early therapeutic interventions could help caregivers identify their needs,
      increase knowledge about changes in roles and relationship reciprocity, and focus
      on enhancement of the positive, intact experiences to prevent caregiver burden.

PMID- 25566687
TI  - Theoretical perspectives on the infectiousness of Ebola virus disease.
AB  - BACKGROUND: Ebola virus disease (EVD) has generated a large epidemic in West
      Africa since December 2013. This mini-review is aimed to clarify and illustrate
      different theoretical concepts of infectiousness in order to compare the
      infectiousness across different communicable diseases including EVD. METHODS: We
      employed a transmission model that rests on the renewal process in order to
      clarify theoretical concepts on infectiousness, namely the basic reproduction
      number, R0, which measures the infectiousness per generation of cases, the force
      of infection (i.e. the hazard rate of infection), the intrinsic growth rate (i.e.
      infectiousness per unit time) and the per-contact probability of infection (i.e.
      infectiousness per effective contact). RESULTS: Whereas R0 of EVD is similar to
      that of influenza, the growth rate (i.e. the measure of infectiousness per unit
      time) for EVD was shown to be comparatively lower than that for influenza.
      Moreover, EVD and influenza differ in mode of transmission whereby the
      probability of transmission per contact is lower for EVD compared to that of
      influenza. CONCLUSIONS: The slow spread of EVD associated with the need for
      physical contact with body fluids supports social distancing measures including
      contact tracing and case isolation. Descriptions and interpretations of different
      variables quantifying infectiousness need to be used clearly and objectively in
      the scientific community and for risk communication.

PMID- 25566689
TI  - Highly reduced graphene oxide supported Pt nanocomposites as highly efficient
      catalysts for methanol oxidation.
AB  - The highly reduced graphene oxide using solvated electrons as reductive agents
      shows low defects and well dispersion that are vital as the support of Pt
      nanoparticles in direct methanol electro-oxidation. The electrochemical
      experiments demonstrate that the Pt/RGO composites not only greatly enhance the
      catalytic activity but also dramatically improve the durability of the catalyst. 

PMID- 25566690
TI  - Inter-cluster distance dependence of electrical conduction in nanocluster
      assembled films of silver: a new paradigm for design of nanostructures.
AB  - The transport properties of films assembled from metal nanoclusters can be
      significantly different from the metals in their bulk or thin film forms due to
      quantum confinement effects and several competing energy and length scales. For a
      film composed of metal nanoclusters as its building blocks, the cluster size and
      the inter-cluster separation are parameters that can be varied experimentally.
      Here we show that the electrical conductivity of a film composed of silver
      nanoclusters can be changed by 9 orders of magnitude as a function of the average
      inter-cluster separation while keeping the average cluster size same. For inter
      cluster separations of 9 nanometres or more the conductivity is insulating type
      whereas for lesser inter-cluster separations the conductivity behaviour is
      metallic type with a positive temperature coefficient of resistance. In the
      intermediate range between the two regions, a very interesting temperature
      independent conductivity is seen. Our work provides a new paradigm for design of
      artificial solid structures composed of nanoclusters. The properties of these
      nanostructures could be tuned by varying the inter-cluster distances to get the
      desired properties in the same material. 

PMID- 25566688
TI  - Pneumonia severity, comorbidity and 1-year mortality in predominantly older
      adults with community-acquired pneumonia: a cohort study.
AB  - BACKGROUND: In patients with community-acquired pneumonia (CAP), short-term
      mortality is largely dependent on pneumonia severity, whereas long-term mortality
      is considered to depend on comorbidity. However, evidence indicates that severity
      scores used to assist management decisions at disease onset may also be
      associated with long-term mortality. Therefore, the objective of the study was to
      investigate the performance of the pneumonia severity scores CURB-65 and CRB-65
      compared to the Charlson Comorbidity Index (CCI) for predicting 1-year mortality
      in adults discharged from hospital after inpatient treatment for CAP. METHODS:
      From a single centre, all cases of patients with CAP treated consecutively as
      inpatients between 2005 and 2009 and surviving at least 30 days after admission
      were analysed. The patients' vital status was obtained from the relevant local
      register office. CURB-65, CRB-65 and CCI were compared using receiver operating
      characteristics (ROC) analysis. RESULTS: Of 498 cases analysed, 106 (21.3%)
      patients died within 1 year. In univariate analysis, age >=65 years, nursing home
      residency, hemiplegia, dementia and congestive heart failure were significantly
      associated with mortality. CURB-65, CRB-65 and CCI were also all associated with
      mortality at 1 year. ROC analysis yielded a weak, yet comparable test performance
      for CURB-65 (AUC and corresponding 95% confidence interval [CI] for risk
      categories: 0.652 [0.598-0.706]) and CCI (AUC [CI]: 0.631 [0.575-0.688]; for CRB
      65 0.621 [0.565-0.677] and 0.590 [0.533-0.646]). CONCLUSIONS: Neither CURB-65 or
      CRB-65 nor CCI allow excellent discrimination in terms of predicting longer term
      mortality. However, CURB-65 is significantly associated with long-term mortality
      and performed equally to the CCI in this respect. This fact may help to identify
      CAP survivors at higher risk after discharge from hospital.

PMID- 25566691
TI  - Soliton instability and fold formation in laterally compressed graphene.
AB  - We investigate-through simulations and analytical calculations-the consequences
      of uniaxial lateral compression applied to the upper layer of multilayer
      graphene. The simulations of compressed graphene show that strains larger than
      2.8% induce soliton-like deformations that further develop into large, mobile
      folds. Such folds were indeed experimentally observed in graphene and other solid
      lubricants two-dimensional (2D) materials. Interestingly, in the soliton-fold
      regime, the shear stress decreases with the strain s, initially as s(-2/3) and
      rapidly going to zero. Such instability is consistent with the recently observed
      negative dynamic compressibility of 2D materials. We also predict that the
      curvatures of the soliton-folds are given by r(c) = delta?(beta/2alpha) where 1
      <= delta <= 2 and beta and alpha are respectively related to the layer bending
      modulus and to the interlayer binding energy of the material. This finding might
      allow experimental estimates of the beta/alpha ratio of 2D materials from fold
      morphology.

PMID- 25566692
TI  - [Occupational exposure to blood in multiple trauma care].
AB  - BACKGROUND: Trauma care personnel are at risk of occupational exposure to blood
      borne pathogens. Little is known regarding compliance with standard precautions
      or occupational exposure to blood and body fluids among multiple trauma care
      personnel in Germany. AIM: Compliance rates of multiple trauma care personnel in
      applying standard precautions, knowledge about transmission risks of blood-borne
      pathogens, perceived risks of acquiring hepatitis B, hepatitis C and human
      immunodeficiency virus (HIV) and the personal attitude towards testing of the
      index patient for blood-borne pathogens after a needlestick injury were
      evaluated. MATERIAL AND METHODS: In the context of an advanced multiple trauma
      training an anonymous questionnaire was administered to the participants.
      RESULTS: Almost half of the interviewees had sustained a needlestick injury
      within the last 12 months. Approximately three quarters of the participants were
      concerned about the risk of HIV and hepatitis. Trauma care personnel had
      insufficient knowledge of the risk of blood-borne pathogens, overestimated the
      risk of hepatitis C infection and underused standard precautionary measures.
      Although there was excellent compliance for using gloves, there was poor
      compliance in using double gloves (26.4 %), eye protectors (19.7 %) and face
      masks (15.8 %). The overwhelming majority of multiple trauma care personnel
      believed it is appropriate to test an index patient for blood-borne pathogens
      following a needlestick injury. CONCLUSION: The process of treatment in
      prehospital settings is less predictable than in other settings in which invasive
      procedures are performed. Periodic training and awareness programs for trauma
      care personnel are required to increase the knowledge of occupational infections
      and the compliance with standard precautions. The legal and ethical aspects of
      testing an index patient for blood-borne pathogens after a needlestick injury of
      a healthcare worker have to be clarified in Germany.

PMID- 25566695
TI  - Construction and analysis of a protein-protein interaction network related to
      self-renewal of mouse spermatogonial stem cells.
AB  - Spermatogonial stem cells (SSCs) are responsible for sustained spermatogenesis
      throughout the reproductive life of the male. Extensive studies of SSCs have
      identified dozens of genes that play important roles in sustaining or controlling
      the pool of SSCs in the mammalian testis. However, there is still limited
      knowledge of whether or how these key genes interact with each other during SSC
      self-renewal. Here, we constructed a protein-protein interaction (PPI) network
      for SSC self-renewal based on interactions between 23 genes essential for SSC
      self-renewal, which were obtained from a text mining system, and the interacting
      partners of the 23 key genes, which were differentially expressed in SSCs. The
      SSC self-renewal PPI network consisted of 246 nodes connected by 844 edges.
      Topological analyses of the PPI network were conducted to identify genes
      essential for maintenance of SSC self-renewal. The subnetwork of the SSC self
      renewal network suggested that the 23 key genes involved in SSC self-renewal were
      connected together through other 94 genes. Clustering of the whole network and
      subnetwork of SSC self-renewal revealed several densely connected regions,
      implying significant molecular interaction modules essential for SSC self
      renewal. Notably, we found the 23 genes to be responsible for SSC self-renewal by
      forming a continuous PPI network centered on Pou5f1. Our study indicates that it
      is feasible to explore important proteins and regulatory pathways in biological
      activities by combining a PPI database with the high-throughput data of gene
      expression profiles. 

PMID- 25566694
TI  - Effect of Hemoglobin Transfusion Threshold on Cerebral Hemodynamics and
      Oxygenation.
AB  - Cerebral dysfunction caused by traumatic brain injury may adversely affect
      cerebral hemodynamics and oxygenation leading to worse outcomes if oxygen
      capacity is decreased due to anemia. In a randomized clinical trial of 200
      patients comparing transfusion thresholds <7 g/dl versus 10 g/dl, where
      transfusion of leukoreduced packed red blood cells was used to maintain the
      assigned hemoglobin threshold, no long-term neurological difference was detected.
      The current study examines secondary outcome measures of intracranial pressure
      (ICP), cerebral perfusion pressure (CPP), and brain tissue oxygenation (PbtO2) in
      patients enrolled in this randomized clinical trial. We observed a lower hazard
      for death (hazard ratio [HR]=0.12, 95% confidence interval [CI]=0.02-0.99) during
      the first 3 days post-injury, and a higher hazard for death after three days
      (HR=2.55, 95% CI=1.00-6.53) in the 10 g/dl threshold group as compared to the 7
      g/dL threshold group. No significant differences were observed for ICP and CPP
      but MAP was slightly lower in the 7 g/dL group, although the decreased MAP did
      not result in increased hypotension. Overall brain tissue hypoxia events were not
      significantly different in the two transfusion threshold groups. When the PbtO2
      catheter was placed in normal brain, however, tissue hypoxia occurred in 25% of
      patients in the 7 g/dL threshold group, compared to 10.2% of patients in the 10
      g/dL threshold group (p=0.04). Although we observed a few differences in
      hemodynamic outcomes between the transfusion threshold groups, none were of major
      clinical significance and did not affect long-term neurological outcome and
      mortality. 

PMID- 25566696
TI  - Thermally reduced kaolin-graphene oxide nanocomposites for gas sensing.
AB  - Highly sensitive graphene-based gas sensors can be made using large-area single
      layer graphene, but the cost of large-area pure graphene is high, making the
      simpler reduced graphene oxide (rGO) an attractive alternative. To use rGO for
      gas sensing, however, require a high active surface area and slightly different
      approach is needed. Here, we report on a simple method to produce kaolin-graphene
      oxide (GO) nanocomposites and an application of this nanocomposite as a gas
      sensor. The nanocomposite was made by binding the GO flakes to kaolin with the
      help of 3-Aminopropyltriethoxysilane (APTES). The GO flakes in the nanocomposite
      were contacting neighboring GO flakes as observed by electron microscopy. After
      thermal annealing, the nanocomposite become conductive as showed by sheet
      resistance measurements. Based on the conductance changes of the nanocomposite
      films, electrical gas sensing devices were made for detecting NH3 and HNO3. These
      devices had a higher sensitivity than thermally annealed multilayer GO films.
      This kaolin-GO nanocomposite might be useful in applications that require a low
      cost material with large conductive surface area including the demonstrated gas
      sensors. 

PMID- 25566698
TI  - Metabolic engineering of the fungal D-galacturonate pathway for L-ascorbic acid
      production.
AB  - BACKGROUND: Synthetic L-ascorbic acid (vitamin C) is widely used as a
      preservative and nutrient in food and pharmaceutical industries. In the current
      production method, D-glucose is converted to L-ascorbic acid via several
      biochemical and chemical steps. The main source of L-ascorbic acid in human
      nutrition is plants. Several alternative metabolic pathways for L-ascorbic acid
      biosynthesis are known in plants. In one of them, D-galacturonic acid is the
      precursor. D-Galacturonic acid is also the main monomer in pectin, a plant cell
      wall polysaccharide. Pectin is abundant in biomass and is readily available from
      several waste streams from fruit and sugar processing industries. RESULTS: In the
      present work, we engineered the filamentous fungus Aspergillus niger for the
      conversion of D-galacturonic acid to L-ascorbic acid. In the generated pathway,
      the native D-galacturonate reductase activity was utilized while the gene coding
      for the second enzyme in the fungal D-galacturonic acid pathway, an L-galactonate
      consuming dehydratase, was deleted. Two heterologous genes coding for enzymes
      from the plant L-ascorbic acid pathway--L-galactono-1,4-lactone lactonase from
      Euglena gracilis (EgALase) and L-galactono-1,4-lactone dehydrogenase from
      Malpighia glabra (MgGALDH)--were introduced into the A. niger strain.
      Alternatively, an unspecific L-gulono-1,4-lactone lactonase (smp30) from the
      animal L-ascorbic acid pathway was introduced in the fungal strain instead of the
      plant L-galactono-1,4-lactone lactonase. In addition, a strain with the
      production pathway inducible with D-galacturonic acid was generated by using a
      bidirectional and D-galacturonic acid inducible promoter from the fungus. Even
      though, the lactonase enzyme activity was not observed in the resulting strains,
      they were capable of producing L-ascorbic acid from pure D-galacturonic acid or
      pectin-rich biomass in a consolidated bioprocess. Product titers up to 170 mg/l
      were achieved. CONCLUSIONS: In the current study, an L-ascorbic acid pathway
      using D-galacturonic acid as a precursor was introduced to a microorganism for
      the first time. This is also the first report on an engineered filamentous fungus
      for L-ascorbic acid production and a proof-of-concept of consolidated bioprocess
      for the production.

PMID- 25566697
TI  - Pretreatment (18)F-FDG uptake heterogeneity can predict survival in patients with
      locally advanced nasopharyngeal carcinoma--a retrospective study.
AB  - BACKGROUND: Intratumoural heterogeneity has been demonstrated to be a strong
      indicator of malignant transformation. Our study was to investigate pretreatment
      (18)F-FDG parameters, including (18)F-FDG based heterogeneity for predicting
      survival in patients with locally advanced nasopharyngeal carcinoma (NPC).
      METHODS: Forty newly diagnosed, biopsy-proven locally advanced NPC patients who
      underwent (18)F-FDG PET/CT were retrospectively included. The following PET
      parameters were assessed: maximum and mean standardised uptake value (SUVmax and
      SUVmean), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and
      intratumoral heterogeneity index (HI). The previous parameters were recorded both
      for the primary tumor (-T) and neck lymph nodes (-N). The following endpoints
      were evaluated: local control (LC), progression-free survival (PFS) and overall
      survival (OS). The survival analyses were performed using the Kaplan-Meier
      method. Univariate analysis was performed using the log-rank test. RESULTS:
      Patients with a lower HI-T, SUVmax-T, SUVmean-T and TLG-T had significantly
      better 2-year LC. In predicting PFS, we found that both lower HI-T and HI-N had
      significantly better prognosis. However, the OS was only statistically associated
      with HI-T. CONCLUSION: (18)F-FDG based heterogeneity appears to be an potential
      predicator of patient survival after treatment.

PMID- 25566700
TI  - Toward structure prediction of cyclic peptides.
AB  - Cyclic peptides are a promising class of molecules that can be used to target
      specific protein-protein interactions. A computational method to accurately
      predict their structures would substantially advance the development of cyclic
      peptides as modulators of protein-protein interactions. Here, we develop a
      computational method that integrates bias-exchange metadynamics simulations, a
      Boltzmann reweighting scheme, dihedral principal component analysis and a
      modified density peak-based cluster analysis to provide a converged structural
      description for cyclic peptides. Using this method, we evaluate the performance
      of a number of popular protein force fields on a model cyclic peptide. All the
      tested force fields seem to over-stabilize the alpha-helix and PPII/beta regions
      in the Ramachandran plot, commonly populated by linear peptides and proteins. Our
      findings suggest that re-parameterization of a force field that well describes
      the full Ramachandran plot is necessary to accurately model cyclic peptides. 

PMID- 25566699
TI  - Anticoagulation for the treatment of portal vein thrombosis in liver cirrhosis: a
      systematic review and meta-analysis of observational studies.
AB  - BACKGROUND & AIMS: Systematic review and meta-analysis were performed to evaluate
      the safety and efficacy of anticoagulation for the treatment of portal vein
      thrombosis (PVT) in cirrhotic patients. METHODS: The PubMed, EMBASE, Cochrane
      Library, and ScienceDirect databases were searched. The rates of bleeding
      complications and portal vein recanalization in patients who received
      anticoagulant therapy were pooled. The odds ratio (OR) with 95% confidence
      interval (CI) was calculated to express the difference in the rate of portal vein
      recanalization between anticoagulation and non-anticoagulation groups. All meta
      analyses were conducted by using a random-effects model. RESULTS: Sixteen of 960
      initially identified papers were included. Two studies reported a low incidence
      of major anticoagulation-related complications (4% [2/55] and 3% [1/33]), but no
      lethal complications occurred. The rate of anticoagulation-related bleeding
      ranged from 0% to 18% with a pooled rate of 3.3% (95% CI=1.1%-6.7%). The
      heterogeneity was not significant in the meta-analysis. The total rate of portal
      vein recanalization ranged from 37% to 93% with a pooled rate of 66.6% (95%
      CI=54.7%-77.6%). The rate of complete portal vein recanalization ranged from 0%
      to 75% with a pooled rate of 41.5% (95% CI=29.2%-54.5%). However, the
      heterogeneity was significant in the 2 meta-analyses. The rate of complete portal
      vein recanalization was significantly higher in anticoagulation group than in non
      anticoagulation group (OR=4.16, 95% CI=1.88-9.20, P=0.0004). The heterogeneity
      was not significant in the meta-analysis. CONCLUSION: Anticoagulation could
      achieve a relatively high rate of portal vein recanalization in cirrhotic
      patients with PVT. Given that only a small number of non-randomized comparative
      studies are reported, randomized controlled trials are warranted to confirm the
      risk-to-benefit of anticoagulation in such patients, especially anticoagulation
      related bleeding.

PMID- 25566701
TI  - Evolutionary change: the new face of Annals of Cardiac Anesthesia.

PMID- 25566702
TI  - Is cardiac anaesthesiologist the best person to look after cardiac critical care?

PMID- 25566693
TI  - Digging deep into "dirty" drugs - modulation of the methylation machinery.
AB  - DNA methylation and histone modification are epigenetic mechanisms that result in
      altered gene expression and cellular phenotype. The exact role of methylation in
      myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) remains unclear.
      However, aberrations (e.g. loss-/gain-of-function or up-/down-regulation) in
      components of epigenetic transcriptional regulation in general, and of the
      methylation machinery in particular, have been implicated in the pathogenesis of
      these diseases. In addition, many of these components have been identified as
      therapeutic targets for patients with MDS/AML, and are also being assessed as
      potential biomarkers of response or resistance to hypomethylating agents (HMAs).
      The HMAs 5-azacitidine (AZA) and 2'-deoxy-5-azacitidine (decitabine, DAC) inhibit
      DNA methylation and have shown significant clinical benefits in patients with
      myeloid malignancies. Despite being viewed as mechanistically similar drugs, AZA
      and DAC have differing mechanisms of action. DAC is incorporated 100% into DNA,
      whereas AZA is incorporated into RNA (80-90%) as well as DNA (10-20%). As such,
      both drugs inhibit DNA methyltransferases (DNMTs; dependently or independently of
      DNA replication) resulting in the re-expression of tumor-suppressor genes;
      however, AZA also has an impact on mRNA and protein metabolism via its inhibition
      of ribonucleotide reductase, resulting in apoptosis. Herein, we first give an
      overview of transcriptional regulation, including DNA methylation, post
      translational histone-tail modifications, the role of micro-RNA and long-range
      epigenetic gene silencing. We place special emphasis on epigenetic
      transcriptional regulation and discuss the implication of various components in
      the pathogenesis of MDS/AML, their potential as therapeutic targets, and their
      therapeutic modulation by HMAs and other substances (if known). The main focus of
      this review is laid on dissecting the rapidly evolving knowledge of AZA and DAC
      with a special focus on their differing mechanisms of action, and the effect of
      HMAs on transcriptional regulation. 

PMID- 25566703
TI  - Diastolic function and new-onset atrial fibrillation following cardiac surgery.
AB  - BACKGROUND: Numerous studies have reported predictors of new-onset postoperative
      atrial fibrillation (POAF) following cardiac surgery, which is associated with
      increased length of stay, cost of care, morbidity, and mortality. The purpose of
      this study was to examine the association between preoperative diastolic function
      and occurrence of new-onset POAF in patients undergoing a variety of cardiac
      surgeries at a single institution. METHODS: Using data from a prospective study
      from November 2007 to January 2010, a retrospective review was conducted. The
      diastolic function of each patient was determined from preoperative transthoracic
      echocardiograms. Occurrence of new-onset POAF was prospectively noted for each
      patient in the original study. Demographic and operative characteristics of the
      study population were analyzed to determine predictors of POAF. RESULTS: Of 223
      patients, 91 (40.8%) experienced new-onset POAF. Univariate predictors of POAF
      included increasing age, male gender, operations involving mitral valve
      repair/replacement, nonsmoking, hypertension, increased intraoperative pulmonary
      artery pressure, grade I diastolic dysfunction, abnormal diastolic function of
      any grade, decreased medial e', elevated medial E/e', and increased left atrial
      volume. Multivariate predictors of POAF included increasing age, increased left
      atrial volume, and elevated initial intraoperative pulmonary artery pressure.
      Even after exclusion of patients with hypertrophic obstructive cardiomyopathy or
      those undergoing mitral valve operations, diastolic dysfunction was not a
      multivariate predictor of POAF. CONCLUSIONS: In the patient population studied
      here, preoperative diastolic dysfunction was not predictive of POAF. In addition
      to increasing age, initial intraoperative pulmonary artery systolic pressure and
      left atrial volume were both significant multivariate predictors of POAF.

PMID- 25566704
TI  - The analgesic efficacy of continuous presternal bupivacaine infusion through a
      single catheter after cardiac surgery.
AB  - BACKGROUND: Median sternotomy, sternal spreading, and sternal wiring are the main
      causes of pain during the early recovery phase following cardiac surgery. AIM:
      This study was designed to evaluate the analgesic efficacy of continuous
      presternal bupivacaine infusion through a single catheter after parasternal block
      following cardiac surgery. MATERIALS AND METHODS: The total of 40 patients
      (American Society of Anesthesiologist status II, III), 45-60 years old,
      undergoing coronary-artery bypass grafting were enrolled in this prospective,
      randomized, double-blind study. A presternal catheter was inserted with
      continuous infusion of 5 mL/h bupivacaine 0.25% (Group B) or normal saline (Group
      C) during the first 48 postoperative hrs. Primary outcomes were postoperative
      morphine requirements and pain scores, secondary outcomes were extubation time,
      postoperative respiratory parameters, incidence of wound infection, Intensive
      Care Unit (ICU) and hospital stay duration, and bupivacaine level in blood.
      STATISTICAL METHODS: Student's t-test was used to analyze the parametric data and
      Chi-square test for categorical variables. RESULTS: During the postoperative 48
      h, there was marked reduction in morphine requirements in Group B compared to
      Group C, (8.6 +/- 0.94 mg vs. 18.83 +/- 3.4 mg respectively, P = 0.2), lower
      postoperative pain scores, shorter extubation time (117 +/- 10 min vs. 195 +/- 19
      min, respectively, P = 0.03), better respiratory parameters (PaO 2 /FiO 2, PaCO 2
      and pH), with no incidence of wound infection, no differences in ICU or hospital
      stay duration. The plasma concentration of bupivacaine remained below the toxic
      threshold (at T24, 1.2 ug/ml +/- 0.3 and T48 h 1.7 +/- 0.3 ug/ml). CONCLUSION:
      Continuous presternal bupivacaine infusion has resulted in better postoperative
      analgesia, reduction in morphine requirements, shorter time to extubation, and
      better postoperative respiratory parameters than the control group.

PMID- 25566705
TI  - The analgesic efficacy of continuous presternal bupivacaine infusion through a
      single catheter after cardiac surgery: a commentary.

PMID- 25566706
TI  - Efficacy of tranexamic acid as compared to aprotinin in open heart surgery in
      children.
AB  - BACKGROUND: Coagulopathy is a major issue in children undergoing high-risk
      pediatric cardiac surgery. Use of anti-fibrinolytics is well documented in
      adults, but recently there are questions raised about safety and effectiveness of
      their use on routine use. Tranexamic acid is a potent anti-fibrinolytic, but its
      role is not fully understood in children. This study aims to study the benefits
      tranexamic acid in controlling postoperative bleeding in pediatric cardiac
      surgical patients. METHODS AND RESULTS: Fifty consecutive children who underwent
      cardiac surgery were randomized prospectively to receive either aprotinin (Group
      A; n = 24) or tranexamic acid (Group B; n = 26) from September 2009 to February
      2010 were studied. Primary end points were early mortality, postoperative
      drainage, reoperation for bleeding and complications. Mean age and body weight
      was smaller in Group A (Age: 48.55 vs. 64.73 months; weight 10.75 vs. 14.80 kg)
      respectively. Group A had more cyanotic heart disease than Group B (87.5% vs.
      76.92%). Mean cardiopulmonary bypass time (144.33 vs. 84.34 min) and aortic cross
      clamp time (78.5 vs. 41.46 min) were significantly higher in group A. While the
      blood and products usage was significantly higher in Group A, there was no
      difference in indexed postoperative drainage in first 4, 8 and 12 h and
      postoperative coagulation parameters. Mean C-reactive protein was less in Group A
      than B and renal dysfunction was seen more in Group A (25% vs. 7.6%). Mortality
      in Group A was 16.66% and 7.6% in Group B. CONCLUSION: Anti-fibrinolytics have a
      definitive role in high-risk children who undergo open-heart surgery. Tranexamic
      acid is as equally effective as aprotinin with no additional increase in
      morbidity or mortality.

PMID- 25566707
TI  - Comparison of tranexamic acid with aprotinin in pediatric cardiac surgery.

PMID- 25566708
TI  - Pediatric cardiac catheterization procedure with dexmedetomidine sedation:
      radiographic airway patency assessment.
AB  - AIMS: The aim of the study was to measure airway patency objectively during
      dexmedetomidine sedation under radiographic guidance in spontaneously breathing
      pediatric patients scheduled for cardiac catheterization procedures. SUBJECTS AND
      METHODS: Thirty-five patients in the age group 5-10 years scheduled for cardiac
      catheterization procedures were enrolled. All study patients were given loading
      dose of dexmedetomidine at 1 mg/kg/min for 10 min and then maintenance dose of
      1.5 mg/kg/h. Radiographic airway patency was assessed at the start of infusion (0
      min) and after 30 min. Antero-posterior (AP) diameters were measured manually at
      the nasopharyngeal and retroglossal levels. Dynamic change in airway between
      inspiration and expiration was considered a measure of airway collapsibility.
      Patients were monitored for hemodynamics, recovery time and complications.
      STATISTICAL ANALYSIS: Student paired t-test was used for data analysis. P < 0.05
      was considered significant. RESULTS: Minimum and maximum AP diameters were
      compared at 0 and 30 min. Nasopharyngeal level showed significant reduction in
      the minimum (6.27 +/- 1.09 vs. 4.26 +/- 1.03, P < 0.0001) and maximum (6.51 +/-
      1.14 vs. 5.99 +/- 1.03, P < 0.0001) diameters. Similarly retroglossal level
      showed significant reduction in the minimum (6.98 +/- 1.09 vs. 5.27 +/- 1.15, P <
      0.0001) and maximum (7.49 +/- 1.22 vs. 6.92 +/- 1.12, P < 0.0003) diameters. The
      degree of collapsibility was greater at 30 min than baseline ( P < 0.0001). There
      was a significant decrease in heart rate ( P < 0.0001), and the average recovery
      time was 39.86 +/- 12.22 min. CONCLUSION: Even though airway patency was
      maintained in all children sedated with dexmedetomidine, there were significant
      reductions in the upper airway dimensions measured, so all precautions to manage
      the airway failure should be taken.

PMID- 25566709
TI  - Efficacy of cardiac resynchronization with defibrillator insertion in patients
      undergone coronary artery bypass graft: a cohort study of cardiac function.
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) is a proven therapeutic
      method in selected patients with heart failure and systolic dysfunction which
      increases left ventricular function and patient survival. We designed a study
      that included patients undergoing coronary artery bypass graft (CABG), with and
      without CRT-defibrillator (CRT-D) inserting and then measured its effects on
      these two groups. PATIENTS AND METHODS: Between 2010 and 2013, we conducted a
      prospective cohort study on 100 coronary artery disease patients where candidate
      for CABG. Then based on the receiving CRT-D, the patients were categorized in two
      groups; Group 1 ( n = 48, with CRT-D insertion before CABG) and Group 2 ( n = 52
      without receiving CRT-D). Thereafter both of these groups were followed-up at 1-3
      months after CABG for mortality, hospitalization, atrial fibrillation (AF),
      echocardiographic assessment, and New York Heart Association (NYHA) class level.
      RESULTS: The mean age of participants in Group 1 (48 male) and in Group 2 (52
      male) was 58 +/- 13 and 57 +/- 12 respectively. Difference between Groups 1 and 2
      in cases of mean left ventricular ejection fraction (LVEF) changes and NYHA class
      level was significant ( P > 0.05). Hospitalization ( P = 0.008), mortality rate (
      P = 0.007), and AF were significantly different between these two groups.
      CONCLUSIONS: The results showed that the increase in LVEF and patient's
      improvement according to NYHA-class was significant in the first group, and
      readmission, mortality rate and AF was increased significantly in the second
      group.

PMID- 25566710
TI  - Urinary neutrophil gelatinase-associated lipocalin time course during cardiac
      surgery.
AB  - BACKGROUND: NGAL is one of the most promising AKI biomarkers in cardiac surgery.
      However, the best timing to dose it and the reference values are still matter of
      discussion. AIM OF THE STUDY: We performed a uNGAL perioperative time course, to
      better understand its perioperative kinetics and its role in AKI diagnosis.
      SETTING OF THE STUDY: San Raffaele University Hospital, cardiac surgery
      department. MATERIAL AND METHODS: We enrolled in this prospective observational
      study 19 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).
      Based on preoperative characteristics, they were divided in low-risk and high
      risk patients. uNGAL measurements were collected at pre-defined times before,
      during, and up to 24 hours after surgery. STATISTICAL ANALYSIS: Data were
      analysed by use of SAS 1999-2001 program or IBM SPSS Statistics. RESULTS: In low
      risk patients, uNGAL had the highest value immediately after general anesthesia
      induction (basal dosage: uNGAL: 12.20ng*ml -1 , IQR 14.00). It later decreased
      significantly (3.40 ng*ml -1 , IQR 4.80; P = 0.006) during CPB, and finally
      return to its original value 24 hours after surgery. In high-risk patients, uNGAL
      increased immediately after surgery; it had the highest value on ICU arrival
      (38,20 ng*ml -1 ; IQR 133,10) and remained high for several hours. A difference
      in uNGAL levels between the two groups was already observed at the end of
      surgery, but it became statistically significant on ICU arrival (P = 0.002).
      CONCLUSION: This study helps to better understand the different kinetics of this
      new biomarker in low-risk and high-risk cardiac patients.

PMID- 25566712
TI  - Impact of the International Quality Improvement Collaborative on outcomes after
      congenital heart surgery: a single center experience in a developing economy.
AB  - BACKGROUND: The International Quality Improvement Collaborative (IQIC) for
      Congenital Heart Surgery in Developing Countries was initiated to decrease
      mortality and major complications after congenital heart surgery in the
      developing world. OBJECTIVE: We sought to assess the impact of IQIC on
      postoperative outcomes after congenital heart surgery at our institution.
      METHODS: The key components of the IQIC program included creation of a robust
      worldwide database on key outcome measures and nurse education on quality driven
      best practices using telemedicine platforms. We evaluated 1702 consecutive
      patients <=18 years undergoing congenital heart surgery in our institute from
      January 2010-December 2012 using the IQIC database. Preoperative variables
      included age, gender, weight at surgery and surgical complexity as per the RACHS
      1 model. The outcome variables included, in- hospital mortality, duration of
      ventilation, intensive care unit (ICU) stay, bacterial sepsis and surgical site
      infection. RESULTS: The 1702 patients included 771(45.3%) females. The median age
      was 8 months (0.03-216) and the median weight was 6.1Kg (1-100). The overall in
      hospital mortality was 3.1%, Over the three years there was a significant decline
      in bacterial sepsis (from 15.1%, to 9.6%, P < 0.001), surgical site infection
      (11.1% to 2.4%, P < 0.001) and duration of ICU stay from 114(8-999) hours to 72
      (18-999) hours (P < 0.001) The decline in mortality from (4.3% to 2.2%) did not
      reach statistical significance. CONCLUSIONS: The inclusion of our institution in
      the IQIC program was associated with improvement in key outcome measures
      following congenital heart surgery over a three year period.

PMID- 25566711
TI  - The role of point-of-care assessment of platelet function in predicting
      postoperative bleeding and transfusion requirements after coronary artery bypass
      grafting.
AB  - OBJECTIVE: OBJECTIVE platelet function assessment after cardiac surgery can
      predict postoperative blood loss, guide transfusion requirements and discriminate
      the need for surgical re-exploration. We conducted this study to assess the
      predictive value of point-of-care testing platelet function using the
      Multiplate(r) device. METHODS: Patients undergoing isolated coronary artery
      bypass grafting were prospectively recruited ( n = 84). Group A ( n = 42)
      patients were on anti-platelet therapy until surgery; patients in Group B ( n =
      42) stopped anti-platelet treatment at least 5 days preoperatively. Multiplate(r)
      and thromboelastography (TEG) tests were performed in the perioperative period.
      Primary end-point was excessive bleeding (>2.5 ml/kg/h) within first 3 h
      postoperative. Secondary end-points included transfusion requirements, re
      exploration rates, intensive care unit and in-hospital stays. RESULTS: Patients
      in Group A had excessive bleeding (59% vs. 33%, P = 0.02), higher re-exploration
      rates (14% vs. 0%, P < 0.01) and higher rate of blood (41% vs. 14%, P < 0.01) and
      platelet (14% vs. 2%, P = 0.05) transfusions. On multivariate analysis,
      preoperative platelet function testing was the most significant predictor of
      excessive bleeding (odds ratio [OR]: 2.3, P = 0.08), need for blood (OR: 5.5, P <
      0.01) and platelet transfusion (OR: 15.1, P < 0.01). Postoperative "ASPI test"
      best predicted the need for transfusion (sensitivity - 0.86) and excessive blood
      loss (sensitivity - 0.81). TEG results did not correlate well with any of these
      outcome measures. CONCLUSIONS: Peri-operative platelet functional assessment with
      Multiplate(r) was the strongest predictor for bleeding and transfusion
      requirements in patients on anti-platelet therapy until the time of surgery.

PMID- 25566714
TI  - Three-dimensional echocardiographic assessment of atrial septal defects.
AB  - Echocardiography provides a useful tool in the diagnosis of many congenital heart
      diseases, including atrial septal defects, and aids in further delineating
      treatment options. Although two-dimensional echocardiography has been the
      standard of care in this regard, technological advancements have made three
      dimensional echocardiography possible, and the images obtained in this new
      imaging modality are able to accurately portray the morphology, location,
      dimensions, and dynamic changes of defects and many other heart structures during
      the cardiac cycle. 

PMID- 25566713
TI  - Anesthetic issues for robotic cardiac surgery.
AB  - As innovative technology continues to be developed and is implemented into the
      realm of cardiac surgery, surgical teams, cardiothoracic anesthesiologists, and
      health centers are constantly looking for methods to improve patient outcomes and
      satisfaction. One of the more recent developments in cardiac surgical practice is
      minimally invasive robotic surgery. Its use has been documented in numerous
      publications, and its use has proliferated significantly over the past 15 years.
      The anesthesiology team must continue to develop and perfect special techniques
      to manage these patients perioperatively including lung isolation techniques and
      transesophageal echocardiography (TEE). This review article of recent scientific
      data and personal experience serves to explain some of the challenges, which the
      anesthetic team must manage, including patient and procedural factors,
      complications from one-lung ventilation (OLV) including hypoxia and hypercapnia,
      capnothorax, percutaneous cannulation for cardiopulmonary bypass, TEE guidance,
      as well as methods of intraoperative monitoring and analgesia. As existing
      minimally invasive techniques are perfected, and newer innovations are
      demonstrated, it is imperative that the cardiothoracic anesthesiologist must
      improve and maintain skills to guide these patients safely through the robotic
      procedure. 

PMID- 25566716
TI  - Use of real-time three-dimensional transesophageal echocardiography in type A
      aortic dissections: advantages of 3D TEE illustrated in three cases.
AB  - Stanford type A aortic dissections often present to the hospital requiring
      emergent surgical intervention. Initial diagnosis is usually made by computed
      tomography; however transesophageal echocardiography (TEE) can further
      characterize aortic dissections with specific advantages: It may be performed on
      an unstable patient, it can be used intra-operatively, and it has the ability to
      provide continuous real-time information. Three-dimensional (3D) TEE has become
      more accessible over recent years allowing it to serve as an additional tool in
      the operating room. We present a case series of three patients presenting with
      type A aortic dissections and the advantages of intra-operative 3D TEE to
      diagnose the extent of dissection in each case. Prior case reports have
      demonstrated the use of 3D TEE in type A aortic dissections to characterize the
      extent of dissection and involvement of neighboring structures. In our three
      cases described, 3D TEE provided additional understanding of spatial
      relationships between the dissection flap and neighboring structures such as the
      aortic valve and coronary orifices that were not fully appreciated with two
      dimensional TEE, which affected surgical decisions in the operating room. This
      case series demonstrates the utility and benefit of real-time 3D TEE during intra
      operative management of a type A aortic dissection. 

PMID- 25566717
TI  - Left ventricular rupture postmitral valve replacement: surviving a catastrophe.
AB  - One of the dreaded mechanical complications of mitral valve replacement (MVR) is
      rupture of the left ventricle (LV). This report describes the early diagnosis and
      successful repair of rupture of posterior wall of LV in an elderly patient who
      underwent MVR. We have discussed the risk factors and perioperative issues
      implicated in such complication. The anesthesiologist as an intra-operative
      echocardiographer can aid in identifying the patient at risk. Though important
      surgical steps are necessary to prevent the complication; nonetheless, the
      anesthesiologist needs to take key measures in the perioperative period. 

PMID- 25566715
TI  - Statistics in clinical research: Important considerations.
AB  - Statistical analysis is one of the foundations of evidence-based clinical
      practice, a key in conducting new clinical research and in evaluating and
      applying prior research. In this paper, we review the choice of statistical
      procedures, analyses of the associations among variables and techniques used when
      the clinical processes being examined are still in process. We discuss methods
      for building predictive models in clinical situations, and ways to assess the
      stability of these models and other quantitative conclusions. Techniques for
      comparing independent events are distinguished from those used with events in a
      causal chain or otherwise linked. Attention then turns to study design, to the
      determination of the sample size needed to make a given comparison, and to
      statistically negative studies. 

PMID- 25566718
TI  - Postoperative rescue closure of patent foramen ovale in the clinical setting of
      acute hypoxemic respiratory failure and stroke following coronary artery bypass
      surgery.
AB  - We describe a case of intraoperative diagnosis and successful deferred
      percutaneous closure of a patent foramen ovale (PFO) in the clinical setting of
      acute refractory hypoxemic respiratory failure and new-onset ischemic stroke in
      an elderly patient after coronary artery bypass graft. Perioperative morbidity
      (i.e. severe hypoxemia, worsening right ventricular dysfunction, and embolic
      stroke) that is potentially related to intraoperatively diagnosed PFO during
      cardiac surgery can complicate management in the Intensive Care Unit and perhaps
      affect the patient's outcome. Although the PFO closure can be challenging in the
      clinical setting of hypoxemic respiratory failure and stroke following cardiac
      surgery, it can be a reasonable perioperative option. 

PMID- 25566719
TI  - Left ventricular mass: myxoma or thrombus?
AB  - Patient with embolic episode should always be evaluated for cardiac mass. Mass in
      left ventricular can be a myxoma or thrombus even in a normal functioning heart.
      In either case, mobile mass with embolic potential should be surgically resected.

PMID- 25566720
TI  - Initial non-opioid based anesthesia in a parturient having severe aortic stenosis
      undergoing cesarean section with aortic valve replacement.
AB  - Pregnancy in presence of severe aortic stenosis (AS) causes worsening of symptoms
      needing further intervention. In the advanced stages of pregnancy, some patients
      may even require aortic valve replacement (AVR) and cesarean delivery in the same
      sitting. Opioid based general anesthesia for combined lower segment cesarean
      section (LSCS) with AVR has been described. However, the use of opioid may lead
      to fetal morbidity and need of respiratory support for the baby. We describe
      successful anesthetic management for LSCS with AVR in a >33 week gravida with
      severe AS and congestive heart failure. We avoided opioids till delivery of the
      baby AVR; the delivered neonate showed a normal APGAR score. 

PMID- 25566722
TI  - In response to "Positive end-expiratory pressure valve malfunctioning detected by
      capnographic and airway pressure waveform".

PMID- 25566721
TI  - Intractable hyperkalemia due to nicorandil induced potassium channel syndrome.
AB  - Nicorandil is a commonly used antianginal agent, which has both nitrate-like and
      ATP-sensitive potassium (K ATP ) channel activator properties. Activation of
      potassium channels by nicorandil causes expulsion of potassium ions into the
      extracellular space leading to membrane hyperpolarization, closure of voltage
      gated calcium channels and finally vasodilatation. However, on the other hand,
      being an activator of K ATP channel, it can expel K + ions out of the cells and
      can cause hyperkalemia. Here, we report a case of nicorandil induced hyperkalemia
      unresponsive to medical treatment in a patient with diabetic nephropathy. 

PMID- 25566723
TI  - Author's reply for comment on "Positive end-expiratory pressure valve
      malfunctioning detected by capnographic and airway pressure waveform".

PMID- 25566724
TI  - Difficult venous catheterization in internal jugular vein.

PMID- 25566725
TI  - Left ventricular false tendon in a patient undergoing mitral valve replacement.

PMID- 25566728
TI  - Imaging the aorta.

PMID- 25566727
TI  - Sutureless left pulmonary vein augmentation for primary endoluminal pulmonary
      vein ostial stenosis: role of pulmonary venous Doppler.

PMID- 25566726
TI  - Double aortic arch as a source of airway obstruction in a child.
AB  - Double aortic arch (DAA) is a congenital vascular anomaly. The diagnosis was
      difficult till the child was symptomatic, and other causes were ruled out. We
      present the interesting images of a child of respiratory distress because of
      tracheal compression from DAA. 

PMID- 25566729
TI  - Imaging the right ventricle.

PMID- 25566731
TI  - The synthesis of ZnO/SnO2 porous nanofibers for dye adsorption and degradation.
AB  - ZnO/SnO2 hetero-nanofibers about 250 nm in diameter and several micrometers in
      length are synthesized via an electrospun method using zinc chloride and stannous
      chloride as inorganic sources. All fibers are composed of many nanoparticles (5
      10 nm) that induce a highly porous structure as well as high surface area. By
      adjusting the ratio of zinc/stannous source, the synthesized porous ZnO/SnO2
      materials show various structures (corrugated fiber and tube), that are a result
      of the different oxidation/decomposition temperatures of the two components.
      Their photodegradation abilities toward various dye wastewaters (methylene blue,
      congo red, eosin red, and methyl orange) are demonstrated, showing fast
      photodegradation and good recycling ability. It is noteworthy that ZnO/SnO2
      exhibits an enhanced photodegradation ability to congo red, ascribed to the high
      adsorption capacity derived from the strong electrostatic interaction between
      ZnO/SnO2 and congo red. Based on the investigation, these porous ZnO/SnO2 hetero
      nanofibers possess versatile potential applications for wastewater purification. 

PMID- 25566730
TI  - Nasal salmon calcitonin blunts bone microstructure alterations in healthy
      postmenopausal women.
AB  - In healthy postmenopausal women, nasal salmon calcitonin blunted distal radius
      and tibia bone microstructure degradation. INTRODUCTION: Nasal salmon calcitonin
      (NSC) has been reported to lower vertebral fracture risk by 33%, but to modestly
      increase spine areal bone mineral density (aBMD) by 1.5%. Thus, NSC may also
      influence bone microstructure, another known determinant of bone strength.
      METHODS: In a randomized, double-blind, placebo-controlled trial, we investigated
      the effects of 200 IU/day NSC on distal radius and tibia bone microstructure (by
      high-resolution 3-dimensional peripheral quantitative computerized tomography),
      aBMD (by dual-energy X-ray absorptiometry), and serum bone turnover markers in
      healthy postmenopausal women. RESULTS: Mean age was 57.6 +/- 0.8 (+/-SEM) and
      57.4 +/- 0.7 in NSC (n = 45) and placebo groups (n = 45), respectively. Mean
      femoral neck T-score was in the osteopenic range; prevalent vertebral fracture
      was 4% in each group. There was no observed between-group difference in the
      primary outcome distal radius BV/TV (-2.8 +/- 0.6% vs. -4.3 +/- 1.0%, NS). By 2
      years, the decrease in distal radius total density vs. baseline was 4.4 +/- 0.7%
      in controls and 2.1 +/- 0.6% in NSC-receiving patients (p < 0.05). Distal radius
      and tibia cortical thickness decreased by 3.7 +/- 1.0 and 2.4 +/- 0.5% in placebo
      (p < 0.05 vs. baseline for both), respectively, but not in the NSC group. Distal
      radius total density and cortical thickness changes were lower in NSC group than
      in placebo (p < 0.05 for both) in the subgroup with baseline C-terminal
      telopeptides (CTX) above the median. By 6 and 12 months, serum CTX decreased by
      17.3 +/- 6.2 and 19.1 +/- 6.6% (both p < 0.05 vs. baseline), respectively, in
      NSC, but remained stable in controls (NS vs. baseline). There was no difference
      in aBMD. NSC was well tolerated, with less arthralgia than the placebo group (14
      vs. 26, p < 0.05). CONCLUSION: Nasal salmon calcitonin blunted the degradation of
      distal radius and tibia bone microstructure in healthy postmenopausal women.

PMID- 25566732
TI  - Pre-treatment apparent diffusion coefficient mapping: differentiation of benign
      from malignant laryngeal lesions.
AB  - OBJECTIVE: To determine whether a threshold apparent diffusion coefficient value
      may help to differentiate laryngeal carcinomas from benign lesions. METHODS:
      Fifty-three patients with laryngeal masses were recruited; four of them were
      excluded because of susceptibility artefacts. In the remaining 49 patients, the
      pathological results showed 32 laryngeal carcinomas and 17 benign lesions. The
      diagnostic value of diffusion-weighted magnetic resonance imaging for the
      identification of malignant lesions was determined. In addition, the agreement
      between diffusion-weighted magnetic resonance imaging and histopathology was
      assessed. Moreover, the sensitivity, specificity, and negative and positive
      predictive values of the apparent diffusion coefficient in detecting benign and
      malignant lesions were analysed. An apparent diffusion coefficient histogram was
      also produced. RESULTS: An apparent diffusion coefficient value of 1.1 * 10-3
      mm2/second produced the best result when used as the cut-off point to
      differentiate malignant from benign masses. CONCLUSION: An apparent diffusion
      coefficient threshold of 1.1 * 10-3 mm2/second is optimal for distinguishing
      laryngeal carcinomas from benign lesions. Apparent diffusion coefficient values
      were lower for patients with laryngeal carcinomas than for those with benign
      lesions.

PMID- 25566733
TI  - [Subjective asymptomatic corneal opacity after Descemet membrane endothelial
      keratoplasty].

PMID- 25566734
TI  - [Unusual course of a chalazion].
AB  - BACKGROUND: A chalazion is a benign, inflammatory tumor of the eyelid caused by
      an obstruction of the excretory duct of a meibomian gland. Usually a chalazion
      shows a slow painless and non-inflammatory progression. Interestingly, sinus
      infections can initially simulate chalazia by causing an orbital involvement with
      eyelid swelling. CASE REPORT: We report the case of a 15-year-old boy with
      frontal and ethmoidal sinusitis with inflammatory orbital infiltration and
      subacute eyelid swelling. The cerebral imaging showed an encapsulated brain
      abscess so that an urgent surgical removal of the abscess cavity was indicated.
      After several neurosurgical procedures a complete remission of the abscess could
      be achieved. In spite of the large abscess in the frontal lobe the boy never
      showed any neurological or psychiatric symptoms. CONCLUSION: In atypical courses
      of a chalazion the clinical picture requires further diagnosis including
      evaluation and imaging in otorhinolaryngology and neurology.

PMID- 25566735
TI  - [Unilateral loss of eyebrows and repeated botulinum toxin injections:
      questionable correlation in essential blepharospasm].

PMID- 25566736
TI  - [Pupil centroid shift: Marketing tool or essential clinical parameter?].
AB  - BACKGROUND: Pupil centroid shift (PCS) is an easily measured parameter which is
      rarely taken into consideration when planning surgery. PURPOSE: The aim of this
      study was to determine the physiological range of PCS and to evaluate its role in
      refractive and cataract surgery. METHODS: The pupil center was measured in 103
      eyes of 103 patients using the newest PCS module of the Allegro Topolyzer Vario
      (Version 1.76r58, Wavelight-Alcon, Erlangen, Germany) and the difference between
      a mesopic and a photopic environment was determined as PCSm. Additionally, these
      measurements were linearly extrapolated to pupil diameters of 2 mm and 7 mm
      (photopic-scotopic, PCSe). The statistical analysis included correlations between
      various demographic and topographic parameters and PCS. RESULTS: The average (+/-
      standard deviation) PCSm was 0.12 +/- 0.08 mm with a range of 0.02-0.53 mm, with
      2 eyes out of 95 (2%) having a PCSm of more than 0.4 mm. The extrapolated PCSe
      was 0.24 +/- 0.16 mm and ranged from 0.03 to 0.78 mm, with 14 eyes out of 95
      (15%) having a PCSe of more than 0.4 mm. Of the 95 eyes 3 (3%) showed a PCSe of
      more than 0.7 mm. There was no correlation between PCS with any of the
      demographic parameters tested. CONCLUSION: Up to 15% of the patients showed a PCS
      of more than 0.4 mm which requires a decision of the (refractive) ophthalmic
      surgeon as to whether the optical zone should be centered on the photopic or
      mesopic/scotopic pupil center. In the 3% of patients with a PCSe value greater
      than 0.7 mm, the implantation of multifocal intraocular lens (IOL) is not
      recommended.

PMID- 25566737
TI  - [Ophthalmological manifestations of Cornelia de Lange syndrome: Case report and
      review of the literature].
AB  - A 2-year-old boy suffering from Cornelia de Lange syndrome, presented with
      mucopurulent ocular discharge and epiphora since birth. Irrigation and probing of
      the nasolacrimal system revealed and successfully treated bilateral nasolacrimal
      duct obstructions. Cornelia de Lange syndrome is characterized not only by
      typical facial features, visceral and urogenital anomalies but also by
      ophthalmological manifestations in 99% of cases. The most common ophthalmological
      disorders are synophrys, blepharitis, epiphora, hypertrichosis of the eyebrows
      and eyelashes, myopia, ptosis and nasolacrimal duct obstruction.

PMID- 25566738
TI  - [Are there diurnal variations in choroidal thickness?].
AB  - PURPOSE: Measurement of diurnal choroidal thickness in healthy eyes to
      investigate thickness variations. METHODS: A total of 30 healthy eyes in 30
      subjects were examined at 6 predefined times within 24 h. Choroidal thickness was
      visualized using the 7-line scan of spectral domain optical coherence tomography
      (OCT) with enhanced depth imaging (Spectralis, Heidelberg Engineering) and
      manually measured by two independent observers. For statistical analyses the mean
      value was calculated. RESULTS: The mean choroidal thickness was 270 +/- 87 um.
      Choroidal thickness changes from baseline ranged between - 47 um and + 41 um.
      There was a statistically significant negative correlation between baseline
      choroidal thickness and the thickness in examinations at 10:30 am, 1:30 pm and
      4:30 pm with the Spearman correlation test. Due to the large diversity in the
      individual diurnal fluctuations, a significant diurnal variation of choroidal
      thickness was not observed. There was a significant negative correlation between
      age and choroidal thickness. CONCLUSIONS: In this study a significant diurnal
      variation of choroidal thickness was not observed. Patient age correlated
      negatively with choroidal thickness.

PMID- 25566739
TI  - A case of Helicobacter pylori-negative intramucosal well-differentiated gastric
      adenocarcinoma with intestinal phenotype.
AB  - A woman in her 30s visited our hospital with stool abnormality.
      Esophagogastroduodenoscopy revealed a depressed lesion on the greater curvature
      of the gastric antrum. The tumor was diagnosed as a well-differentiated tubular
      adenocarcinoma based on the analysis of the biopsy specimen. The rapid urease
      test, histological examination, and serum anti-Helicobacter pylori antibody
      indicated that the patient was Helicobacter pylori negative. Gastric mucosal
      atrophy was not evident on esophagogastroduodenoscopy. Complete cure en bloc
      resection was successfully performed. The tumor was confined to the mucosa (pT1a
      M). Immunohistochemistry showed positive CD10, MUC2, and CDX2 expression and
      negative MUC5AC and MUC6 expression. Thus, the phenotype was diagnosed as the
      intestinal phenotype. Helicobacter pylori-negative, well-differentiated early
      gastric cancer with intestinal phenotype has not been previously reported. Here,
      we report a rare and valuable case of Helicobacter pylori-negative early gastric
      cancer with intestinal phenotype treated by endoscopic submucosal dissection. 

PMID- 25566740
TI  - Placental fractalkine mediates adhesion of THP-1 monocytes to villous
      trophoblast.
AB  - The chemokine fractalkine (CX3CL1) recently attracted increasing attention in the
      field of placenta research due to its dual nature, acting both as membrane-bound
      and soluble forms. While the membrane-bound form mediates flow-resistant adhesion
      of leukocytes to endothelial and epithelial cells via its corresponding receptor
      CX3CR1, the soluble form arises from metalloprotease-dependent shedding and bears
      chemoattractive activity for monocytes, natural killer cells and T cells. In
      human placenta, fractalkine is expressed at the apical microvillous plasma
      membrane of the syncytiotrophoblast, which may enable close physical contact with
      circulating maternal leukocytes. Based on these observations, we tested the
      hypothesis that fractalkine mediates adhesion of monocytes to the villous
      trophoblast. Forskolin-induced differentiation and syncytialization of the
      trophoblast cell line BeWo was accompanied with a substantial upregulation in
      fractalkine expression and led to increased adhesion of the monocyte cell line
      THP-1, which preferentially bound to syncytia. Blocking as well as silencing of
      the fractalkine receptor CX3CR1 proved involvement of the fractalkine/CX3CR1
      system in adherence of THP-1 monocytes to villous trophoblast. Pre-incubation of
      THP-1 monocytes with human recombinant fractalkine as well as silencing of CX3CR1
      expression in THP-1 monocytes significantly impaired their adherence to BeWo
      cells and primary term trophoblasts. The present study suggests fractalkine as
      another candidate among the panel of adhesion molecules enabling stable
      interaction between leukocytes and the syncytiotrophoblast.

PMID- 25566742
TI  - Exploring the genetic counselor's role in facilitating meaning-making: rare
      disease diagnoses.
AB  - The main goal of the constructivist meaning-making framework is to encourage
      grief adaptation through the search for meaning in loss. Strategies to help
      patients construct meaning from their experiences may lead to positive
      adaptation. This strategy has been used in contemporary grief counseling, but it
      may also be beneficial in the genetic counseling scenario. The diagnosis of a
      rare genetic disorder often has considerable psychosocial impact as patients and
      families describe feelings of isolation and hopelessness. Negative experiences
      with healthcare providers often reinforce these feelings. Genetic counselors
      continue to provide education and psychosocial support to patients and families
      with rare genetic disorders, and meaning-making strategies may provide a
      framework for which to help patients and families adapt to these challenging
      diagnoses. In this paper I explore the background of meaning-making counseling
      strategy and describe an experience in which it was used for counseling a family
      with a child with Mowat-Wilson syndrome. I show how a meaning-making framework
      can help families explore and construct meaning from their experiences and
      encourage positive adaptation. I also address the possible limitations of this
      strategy and the need to share additional experiences with this counseling
      framework. Meaning-making can be another tool for genetic counselors to help
      guide families in their grief and adaptation to rare disease diagnoses. I also
      describe qualities and aspects of counseling through the lens of meaning-making
      and stress the importance of addressing psychosocial dimensions of rare disease
      diagnoses. 

PMID- 25566741
TI  - Factors Associated with Uptake of Genetics Services for Hypertrophic
      Cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a common cardiovascular disorder with
      variable expressivity and incomplete penetrance. Clinical guidelines recommend
      consultation with a genetics professional as part of an initial assessment for
      HCM, yet there remains an underutilization of genetics services. We conducted a
      study to assess factors associated with this underutilization within the
      framework of the Health Belief Model (HBM). An online survey was completed by 306
      affected individuals and at risk family members. Thirty-seven percent of
      individuals (113/306) had visited a genetics professional for reasons related to
      HCM. Genetic testing was performed on 53 % (162/306). Individuals who had
      undergone testing were more likely to have seen a genetics professional (p <
      0.001), had relatives with an HCM diagnosis (p = 0.002), and have a known
      familial mutation (p < 0.001). They were also more likely to agree that genetic
      testing would satisfy their curiosity (p < 0.001), provide reassurance (p <
      0.001), aid family members in making healthcare decisions (p < 0.001), and
      encourage them to engage in a healthier lifestyle (p = 0.002). The HBM components
      of cues to action and perceived benefits and barriers had the greatest impact on
      uptake of genetic testing. In order to ensure optimal counseling and care for
      individuals and families with HCM, awareness and education around HCM and genetic
      services should be promoted in both physicians and patients alike.

PMID- 25566743
TI  - Health-Related Quality-of-Life (HRQoL) on an Average of 12 Years After Gastric
      Bypass Surgery.
AB  - BACKGROUND: It is evident that morbidly obese patients have a low health-related
      quality-of-life (HRQoL), and this low HRQoL has become a common reason for them
      to seek bariatric surgery. Several HRQoL studies demonstrate a dramatic
      postoperative improvement, but most of these have had a short follow-up period.
      MATERIAL AND METHODS: An observational, cross-sectional study for HRQoL was
      conducted to study 486 patients (average age of 50.7 +/- 10.0 years, with 84 % of
      them being female) operated with gastric bypass (GBP) in the period 1993 to 2003
      at the University Hospitals of Orebro and Uppsala. Mean follow-up after gastric
      bypass was 11.5 +/- 2.7 years (range 7-17). Two HRQoL instruments were used, SF
      36 and the Obesity-related Problems scale (OP). The study group was compared with
      two control groups, both matched for age and gender, one from the general
      population and one containing morbidly obese patients evaluated and awaiting
      bariatric surgery. RESULTS: The study group scored better in the SF-36 domains
      (all four physical domains and the vitality subscore) and OP scale compared to
      obese controls, but their HRQoL scores were lower than those of the general
      population. HRQoL was better among younger patients and in the following
      subgroups: men, patients with satisfactory weight loss, satisfied with the
      procedure, free from co-morbidities and gastrointestinal symptoms, employment,
      good oral status and those not hospitalised or regularly followed up for non
      bariatric reasons. CONCLUSION: Long-term follow-up after GBP for morbid obesity
      showed better scores in most aspects of HRQoL compared to obese controls but did
      not achieve the levels of the general population. Patients with better medical
      outcome after gastric bypass operation had better HRQoL.

PMID- 25566745
TI  - Minimally invasive HeartWare LVAD implantation through single left thoracotomy.
AB  - Left ventricular assist device (LVAD) is now a routine therapy for advanced heart
      failure. Authors demonstrate a novel technique of LVAD implantation through a
      single left thoracotomy with anastomosis of outflow graft to the arch of aorta.
      The technique avoids sternotomy or additional right thoracotomy, keeps ascending
      aorta clear and puts outflow graft away from the sternum. 

PMID- 25566744
TI  - Sleeve Gastrectomy Does Not Cause Hypertrophy and Reprogramming of Intestinal
      Glucose Metabolism in Rats.
AB  - BACKGROUND: Clinical studies have shown similar rapid improvements in body mass
      and glycemic control after Roux-en-Y gastric bypass (RYGB) and vertical sleeve
      gastrectomy (VSG). Evidence suggests that adaptive intestinal tissue growth and
      reprogramming of intestinal glucose disposal play a key role in the beneficial
      effects on glucose homeostasis after RYGB, but it is not known whether such
      adaptive changes also occur after sleeve gastrectomy. METHODS: High-fat diet
      induced obese rats were subjected to either VSG or RYGB, and intestinal growth
      and functional adaptations were assessed by using morphometric,
      immunohistochemical, and immuno-blot techniques, 3 months after surgery or sham
      surgery. RESULTS: The cross-sectional areas of the Roux and common limbs are
      significantly increased after RYGB compared with sham surgery (Roux limb: 17.1 +/
      4.0 vs. 5.5 +/- 0.1 mm(2); common limb: 11.7 +/- 0.6 vs. 5.1 +/- 0.5 mm(2); p <
      0.01), but the cross-sectional area of the corresponding jejunum is not different
      from controls after VSG. Similarly, mucosal thickness and the number of GLP-1
      cells are not increased after VSG. Protein expression of hexokinase II is
      increased fourfold (p < 0.01) in the Roux limb after RYGB, but not in the jejunum
      after VSG. CONCLUSIONS: Adaptive hypertrophy and reprogramming of glucose
      metabolism in the small intestine are not necessary for VSG to improve body
      composition and glycemic control. The similar beneficial effects of VSG and RYGB
      on glucose homeostasis might be mediated by different mechanisms.

PMID- 25566746
TI  - Monitoring outcomes in children with acquired brain injury (ABI): a Persian
      validation study of Child and Family Follow-up Survey (CFFS).
AB  - AIM: To translate and validate the Child and Family Follow--up Survey (CFFS) in
      Iran. METHODS: 49 cases with Acquired Brain Injury (ABI), and 30 healthy children
      were included and the CFFS was completed. The Pediatric Quality of Life Inventory
      (PedsQL) also was completed. The internal consistency, test-retest reliability,
      known groups comparison and criterion validity were assessed. RESULTS: The mean
      age of participants was 10.9 years. Cronbach's alpha coefficients were Child and
      Adolescent Scale of Participation (CASP) (0.91), Child and Adolescent Factors
      Inventory (CAFI) (0.90) and Child and Adolescent Scale of Environment (CASE)
      (0.89). Reliability, validity and correlation of CASP and CAFI showed
      satisfactory results. Significant correlations among the three CFFS subscale
      scores were observed. These scores were also significantly correlated with the
      total scores of the PedsQL. CONCLUSION: The findings suggest that CFFS is a valid
      measure to monitor long--term outcomes of children and young adolescents with
      ABI.

PMID- 25566748
TI  - Funding, coverage, and access under Thailand's universal health insurance
      program: an update after ten years.
AB  - BACKGROUND: In 2001, Thailand implemented a universal coverage program by
      expanding government-funded health coverage to uninsured citizens and limited
      their out-of-pocket payments to 30 Baht per encounter and, in 2006, eliminated
      out-of-pocket payments entirely. Prior research covering the early years of the
      program showed that the program effectively expanded coverage while a more recent
      paper of the early effects of the program found that improved access from the
      program led to a reduction in infant mortality. OBJECTIVE: We expand and update
      previous analyses of the effects of the 30 Baht program on access and out-of
      pocket payments. DATA AND METHODS: We analyze national survey and governmental
      budgeting data through 2011 to examine trends in health care financing, coverage
      and access, including out-of-pocket payments. RESULTS: By 2011, only 1.64 % of
      the population remained uninsured in Thailand (down from 2.61 % in 2009). While
      government funding increased 75 % between 2005 and 2010, budgetary requests by
      health care providers exceeded approved amounts in many years. The 30 Baht
      program beneficiaries paid zero out-of-pocket payments for both outpatient and
      inpatient care. Inpatient and outpatient contact rates across all insurance
      categories fell slightly over time. CONCLUSIONS: Overall, the statistical results
      suggest that the program is continuing to achieve its goals after 10 years of
      operation. Insurance coverage is now virtually universal, access has been more or
      less maintained, government funding has continued to grow, though at rates below
      requested levels and 30 Baht patients are still guaranteed access to care with
      limited or no out-of-pocket costs. Important issues going forward are the ability
      of the government to sustain continued funding increases while minimizing cost
      sharing.

PMID- 25566749
TI  - Age and body composition influence TSH concentrations after administration of
      rhTSH.
AB  - AIM: Previous studies listed body surface area (BSA), lean body mass (LBM), and
      age as modifying factors on the TSH concentrations after administration of
      recombinant human thyrotropin (rhTSH). The purpose of this study was to identify
      the main modifying factors on serum TSH levels and to compare the stimulation via
      single rhTSH injection after a short thyroid hormone withdrawal (THW) with that
      of the standard stimulating protocol. PATIENTS, METHODS: 106 patients with
      differentiated thyroid cancer (DTC) undergoing radioiodine therapy (RIT) after
      rhTSH administration were obtained through chart review. Two groups were
      evaluated: Group I was treated with a single rhTSH administration after two weeks
      of T3 therapy followed by one week of THW. Group II was stimulated according to
      the international standard protocol via rhTSH injections for two consecutive
      days. Serum TSH concentrations were documented prior to rhTSH administration (day
      1 TSH), one day after (day 3 TSH) and 3-6 days after (mean 4.2 days, day 6 TSH)
      the last rhTSH injection. The following data was collected: age, gender, weight,
      height, BMI, LBM, BSA, residual thyroid tissue, CRP, creatinine, GFR, liver
      enzymes, alkaline phosphatase, cholesterol, and triglycerides. RESULTS: Group I:
      Age combined with anthropometric factors like BMI (TSH increase and day 6 TSH),
      BSA (TSH decrease), and gender (day 6 TSH) are the main modifying factors on
      serum TSH concentrations after rhTSH administration. Group II: Age and lean body
      mass (LBM) showed a significant impact on day 3 TSH, TSH increase (day 3-day 1),
      and TSH decrease (day 6-day 3). Day 6 TSH was found to be influenced by GFR
      (group II). CONCLUSION: Age and anthropometric parameters have significant
      independent influence on TSH concentrations after rhTSH injection in both groups.
      Anthropometric parameters (BSA, LBM) and demographic parameters (female gender)
      show strong influence on TSH concentrations. Further research should be conducted
      to examine the influence of body compartments on TSH levels through measuring
      total body water.

PMID- 25566750
TI  - Erratum to: Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with
      acromegaly for up to 25 months: results from the blinded extension phase of a
      randomized, double-blind, multicenter, Phase III study.

PMID- 25566747
TI  - Combining two repurposed drugs as a promising approach for Alzheimer's disease
      therapy.
AB  - Alzheimer disease (AD) represents a major medical problem where mono-therapeutic
      interventions demonstrated only a limited efficacy so far. We explored the
      possibility of developing a combinational therapy that might prevent the
      degradation of neuronal and endothelial structures in this disease. We argued
      that the distorted balance between excitatory (glutamate) and inhibitory
      (GABA/glycine) systems constitutes a therapeutic target for such intervention. We
      found that a combination of two approved drugs - acamprosate and baclofen -
      synergistically protected neurons and endothelial structures in vitro against
      amyloid-beta (Abeta) oligomers. The neuroprotective effects of these drugs were
      mediated by modulation of targets in GABA/glycinergic and glutamatergic pathways.
      In vivo, the combination alleviated cognitive deficits in the acute Abeta25-35
      peptide injection model and in the mouse mutant APP transgenic model. Several
      patterns altered in AD were also synergistically normalised. Our results open up
      the possibility for a promising therapeutic approach for AD by combining
      repurposed drugs. 

PMID- 25566751
TI  - Bilateral adrenalectomy for Cushing's disease.
AB  - PURPOSE: Review the indications, outcomes, and consequences of bilateral
      adrenalectomy (BLA) in patients with Cushing's disease. METHODS: A literature
      review was performed. RESULTS: The primary therapy for Cushing's disease is
      surgery, with medical therapy and radiation therapy relegated to an adjuvant
      role. BLA is indicated in cases of persistent disease following pituitary surgery
      or in situations where rapid normalization of hypercortisolism is required. When
      performed via the laparoscopic approach, BLA is associated with a significantly
      reduced morbidity compared to the traditional, open approach. Following BLA,
      patients are at risk for adrenal crisis and the concern of Nelson's syndrome.
      However, BLA leads to a rapid resolution of the signs and symptoms of CS and
      leads to an improved long-term quality of life. CONCLUSION: BLA should be
      considered in the treatment algorithm for patients with persistent CD after
      failed pituitary surgery, especially in patients who have severe consequences of
      hypercortisolism or desire pregnancy.

PMID- 25566752
TI  - Subsequent contralateral hip fractures: can at-risk patients be identified? An
      observational study of 5,102 patients.
AB  - PURPOSE: The aim of this study was to evaluate a sample of patients who sustained
      hip fractures during the years 1997-2011 and identify risk factors for a
      subsequent contralateral hip fracture; one-year mortality rates were compared in
      both groups. METHODS: A total of 5,102 patients with hip fractures were
      prospectively studied to identify patients who had also suffered a subsequent,
      contralateral, hip fracture (SCHF). Those patients who had sustained a second
      fracture within 18 months of the initial fracture were then studied. All data
      were statistically processed. RESULTS: Within 18 months of the first fracture, a
      SCHF occurred in 105 patients (2.1 %). These patients were an average of three
      years older than those in the single fracture group. Risk factors for the
      development of a SCHF included: female gender, residing in a residential care
      facility, and limited mobility prior to injury. Trochanteric fractures did not
      represent a statistically significant risk factor for SCHF. More than three
      quarters of patients with subsequent injuries suffered the same type of fractures
      on the opposite side. Patients with subsequent fractures had lower one-year
      mortality rates than patients with only one fracture. CONCLUSION: Patients at
      greatest risk for a SCHF were women with limited mobility who resided in nursing
      homes for the elderly. The lower mortality rate associated with second fractures
      shows that the prognosis for such patients is good. Since the at-risk group is so
      well defined, prophylactic measures for these patients should be utilized in
      order to minimize the risk of additional fractures.

PMID- 25566753
TI  - Plasmodesmata: function and diversity in plant intercellular communication.
      Preface.

PMID- 25566754
TI  - Antibiotics for community-acquired lower respiratory tract infections secondary
      to Mycoplasma pneumoniae in children.
AB  - Background. Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an
      important cause of community-acquired lower respiratory tract infection (LRTI) in
      children. Pulmonary manifestations are typically tracheobronchitis or pneumonia
      but M. pneumoniae is also implicated in wheezing episodes in both asthmatic and
      non-asthmatic individuals. Although antibiotics are used to treat LRTIs, are view
      of several major textbooks offers conflicting advice for using antibiotics in the
      management of M. pneumoniae LRTI in children.Objectives To determine whether
      antibiotics are effective in the treatment of childhood LRTI secondary to M.
      pneumoniae infections acquired in the community.Search methods We searched
      CENTRAL (2014, Issue 3), MEDLINE (1966 to July week 4, 2014), EMBASE (1980 to
      July, 2014), and both WHOICTRP and ClinicalTrials.gov (13 August 2014).Selection
      criteria Randomised controlled trials (RCTs) comparing antibiotics commonly used
      for treating M. pneumoniae (i.e. macrolide, tetracycline or quinolone classes)
      versus placebo, or antibiotics from any other class in the treatment of children
      under 18 years of age with community acquired LRTI secondary to M.
      pneumoniae.Data collection and analysis The review authors independently selected
      trials for inclusion and assessed methodological quality. We extracted and
      analysed relevant data separately and resolved disagreements by consensus.Main
      results A total of 1912 children were enrolled from seven studies. Data
      interpretation was limited by the inability to extract data that referred to
      children with M. pneumoniae. In most studies, clinical response did not differ
      between children randomised to a macrolide antibiotic and children randomised to
      a non-macrolide antibiotic. In one controlled study (of children with recurrent
      respiratory infections, whose acute LRTI was associated with Mycoplasma,
      Chlamydia or both, by polymerase chain reaction and/or paired sera) 100% of
      children treated with azithromycin had clinical resolution of their illness
      compared to 77% not treated with azithromycin at one month. Authors' conclusions
      There is insufficient evidence to draw any specific conclusions about the
      efficacy of antibiotics for this condition in children (although one trial
      suggests macrolides may be efficacious in some children with LRTI secondary to
      Mycoplasma). The use of antibiotics has to be balanced with possible adverse
      events. There is still a need for high quality, double-blinded RCTs to assess the
      efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in
      children.

PMID- 25566755
TI  - Chinese homozygous Machado-Joseph disease (MJD)/SCA3: a case report.
AB  - A young Chinese male patient was identified as homozygous for Machado-Joseph
      disease (MJD)/spinocerebellar ataxia type 3. This patient had a 4-year medical
      history mainly presenting severe ataxia, abnormal eye movement and pyramidal
      signs. Magnetic resonance imaging of the brain and cervical spinal cord revealed
      no obvious abnormality despite the severe symptoms and the findings of an
      electromyogram. However, brainstem auditory evoked potential indicated peripheral
      impairment and visual evoked potential indicated central impairment of his visual
      pathways. Molecular diagnosis revealed the pattern of CAG repeat units of this
      patient was 71/71. This case demonstrates that homozygosity for MJD enhances the
      clinical severity of the disease, which suggests that genetic education is of
      great importance. 

PMID- 25566756
TI  - Chromosome abnormalities diagnosed in utero: a Japanese study of 28 983 amniotic
      fluid specimens collected before 22 weeks gestations.
AB  - To investigate the frequency and type of abnormal karyotype in Japan by
      amniocentesis before 22 weeks of gestation. We performed a retrospective analysis
      of 28 983 amniotic fluid specimens in a local population collected before 22
      weeks gestations for fetal karyotyping. The incidence of abnormal karyotype was
      6.0%. The main indication was advanced maternal age (AMA) of 35 years and older,
      which represented over half of the clinical indications. Abnormal karyotype was
      most frequently reported among the referrals for abnormal ultrasound findings
      (21.8%), followed by positive maternal serum screen results (5.3%). Three-fourths
      of abnormal karyotype was either autosomal aneuploidy (64.0%) or sex chromosome
      aneuploidy (11.6%). Abnormal karyotype was detected in 2.8% of pregnant women
      referred for AMA. Clinically significant abnormal karyotype increased with
      advancing maternal age. The frequency and type of abnormal karyotype detected by
      amniocentesis for various indications were determined. Amniocentesis was mainly
      performed among the referrals for AMA, which is a characteristic distribution of
      indications of Japan. 

PMID- 25566757
TI  - Copy-number variations in Y-chromosomal azoospermia factor regions identified by
      multiplex ligation-dependent probe amplification.
AB  - Although copy-number variations (CNVs) in Y-chromosomal azoospermia factor (AZF)
      regions have been associated with the risk of spermatogenic failure (SF), the
      precise frequency, genomic basis and clinical consequences of these CNVs remain
      unclear. Here we performed multiplex ligation-dependent probe amplification
      (MLPA) analysis of 56 Japanese SF patients and 65 control individuals. We
      compared the results of MLPA with those of conventional sequence-tagged site PCR
      analyses. Eleven simple and complex CNVs, including three hitherto unreported
      variations, were identified by MLPA. Seven of the 11 CNVs were undetectable by
      conventional analyses. CNVs were widely distributed in AZF regions and shared by
      ~60% of the patients and ~40% of the controls. Most breakpoints resided within
      locus-specific repeats. The majority of CNVs, including the most common gr/gr
      deletion, were identified in the patient and control groups at similar
      frequencies, whereas simple duplications were observed exclusively in the patient
      group. The results imply that AZF-linked CNVs are more frequent and heterogeneous
      than previously reported. Non-allelic homologous recombination likely underlies
      these CNVs. Our data confirm the functional neutrality of the gr/gr deletion in
      the Japanese population. We also found a possible association between AZF-linked
      simple duplications and SF, which needs to be evaluated in future studies. 

PMID- 25566759
TI  - Theoretical exploration of MgH2 and graphene nano-flakes in cyclohexane:
      proposing a new perspective toward functional hydrogen storage material.
AB  - We studied the reaction mechanism of di-n-butylmagnesium decomposing into MgH2 in
      cyclohexane, and found a new route easier than famous beta-hydride elimination.
      Further, we explored the dynamic behavior of graphene nano-flakes and MgH2 in
      cyclohexane, and gained new insights for efficient hydrogen storage material
      preparation. 

PMID- 25566758
TI  - Genetic structure among Fijian island populations.
AB  - We examined nine Y chromosome short tandem repeats (Y-STRs) and the mitochondrial
      DNA (mtDNA) hypervariable segment 1 region in the Fijian island populations of
      Viti Levu, Vanua Levu, Kadavu, the Lau islands and Rotuma. We found significant
      genetic structure among these populations for the Y-STRs, both with and without
      the Rotumans, but not for the mtDNA. We also found that all five populations
      exhibited the sex-biased admixture associated with areas settled by Austronesian
      speaking people, with paternal lineages more strongly associated with Melanesian
      populations and maternal lineages more strongly associated with Polynesian
      populations. We also found that the Rotumans in the north and the Lau Islanders
      in the east were genetically more similar to Polynesian populations than were the
      other Fijians, but only for the mtDNA. For the Y-STRs, the Rotumans and the Lau
      Islanders were genetically as similar to Melanesian populations as were the other
      three populations. Of the five populations, the Rotumans were the most different
      in almost every regard. Although past genetic studies treated the Fijians as
      being genetically homogenous despite known geographic, phenotypic, cultural and
      linguistic variation, our findings show significant genetic variation and a need
      for a closer examination of individual island populations within Fiji,
      particularly the Rotumans, in order to better understand the process of the
      peopling of Fiji and of the surrounding regions. 

PMID- 25566760
TI  - Effect of the amino acid composition of cyclic peptides on their self-assembly in
      lipid bilayers.
AB  - The effect of amino acid composition on the formation of transmembrane channels
      in lipid bilayers upon self-assembly of alt-(L,D)-alpha-cyclic octapeptides has
      been investigated. Cyclic peptides comprising D-leucine, alternating with
      different combinations of L-azidolysine, L-lysine(Alloc), L-lysine and L
      tryptophan were synthesized and the size of pores formed via self-assembly of
      these molecules in lipid bilayers was elucidated using large unilamellar vesicle
      fluorescence assays and dynamic light scattering. Pore formation was examined in
      large unilamellar vesicles made up of egg yolk phosphatidylcholine or Escherichia
      coli total lipid extract. From these analyses, we have established that cyclic
      peptides with charged side chains form large pores while those with neutral side
      chains form unimeric pores. Furthermore, the cyclic peptides that consist of non
      symmetric amino acid configurations possess a higher membrane activity than the
      cyclic peptides with a symmetric amino acid configuration. In addition, we have
      found that peptide amphiphilicity plays a vital role in selective partitioning
      between bilayers that consist of egg yolk phosphatidylcholine and those comprised
      of E. coli total lipid extract. These results suggest that selective transbilayer
      channel formation via self-assembly may be a viable alternative for many
      applications that currently use more expensive, multistep synthesis methods.

PMID- 25566761
TI  - Retention in HIV care among female sex workers in the Dominican Republic:
      implications for research, policy and programming.
AB  - There are clear benefits of retention in HIV care, yet millions of people living
      with HIV are sub-optimally retained. This study described factors from Andersen's
      behavioral model that were associated with retention in HIV care among 268 female
      sex workers (FSWs) living with HIV in the Dominican Republic using two measures
      of retention: a 6-month measure of HIV clinic attendance and a measure that
      combined clinic attendance and missed visits. FSWs who ever attended HIV care
      reported high rates (92 %) of 6-month attendance, but 37 % reported missed
      visits. Using the combined retention measure, the odds of being retained in HIV
      care were higher among FSWs with more positive perceptions of HIV service
      providers [adjusted odds ratio (AOR) 1.17; 95 % confidence interval (CI) 01.09,
      1.25] and lower among women who reported recent alcohol consumption (AOR 0.50; 95
      % CI 0.28, 0.92) and self-stigmatizing beliefs related to sex work (AOR 0.93; 95
      % CI 0.88, 0.98). These findings support the hypothesis that retention in HIV
      care may be best determined through a combined measure as missed visits are an
      important mechanism to identify in-care patients who require additional support. 

PMID- 25566762
TI  - Social Media Use and High-Risk Sexual Behavior Among Black Men Who Have Sex with
      Men: A Three-City Study.
AB  - Black men who have sex with men (MSM) bear a disproportionate burden of human
      immunodeficiency (HIV) incidence in the United States. Little research has
      focused on the associations between social media use and sexual behavior among
      Black MSM. 205 Black MSM completed measures assessing social media use and sexual
      behaviors. Men spent an average of 34 h per week on social media sites. 53 %
      arranged sexual hookups online in the previous 3 months, and did so a mean of 10
      times. Overall, users of social media and men who arranged sexual hookups online
      engaged in more risky behaviors than non-users and men who did not arrange sexual
      hookups online. However, partner-level data indicated that men engaged in fewer
      risky behaviors with partners met online compared to partners met in other ways
      such as at bars or through friends. Social media-based interventions designed to
      decrease HIV transmission among racial minority MSM are needed.

PMID- 25566765
TI  - Ratiometric ECL of heterodinuclear Os-Ru dual-emission labels.
AB  - A dual emission of two hererodinuclear Os-Ru labels with a linear calibration
      curve between the ECL intensity ratio (I731/I618) and tripropylamine (TPA)
      concentration was first established. 

PMID- 25566764
TI  - Investigating Patient and Physician Delays in the Diagnosis of Head and Neck
      Cancers: a Canadian Perspective.
AB  - Diagnostic delays for head and neck cancer (HNC) patients are common. Patients
      often disregard symptoms for long periods before seeking help, and some family
      physicians may not be alert to the warning symptoms and signs of HNCs. This study
      evaluated the factors associated with length of delays in the diagnosis of HNCs
      in a Canadian population. This was a mixed-method study consisting of patient
      interviews and surveys in an academic health center. A questionnaire requesting
      demographic and disease information was completed by HNC patients followed by a
      30 min semi-structured interview in a private setting. Interviews were audio
      recorded, transcribed, anonymized, and descriptively coded for emergent themes.
      Twenty-eight head and neck cancer patients participated in the study. More
      patients experienced physician delay (71 %) than patient delay (36 %). The median
      physician delay and patient delay were 108 and 31 days, respectively. Two main
      themes regarding these delays were (1) physician lack of knowledge and (2) lack
      of patient awareness. Results indicate that physician delay needs to be focused
      on compared to patient delay, as it is more common and has longer delays. More
      comprehensive training in head and neck clinical examination skills during
      undergraduate and residency training is recommended to reduce physician delay.
      Patient delay could be targeted by public education programs via both physicians
      and dentists.

PMID- 25566763
TI  - Enhancing Lay Counselor Capacity to Improve Patient Outcomes with Multimedia
      Technology.
AB  - Multimedia technologies offer powerful tools to increase capacity of health
      workers to deliver standardized, effective, and engaging antiretroviral
      medication adherence counseling. Masivukeni-is an innovative multimedia-based,
      computer-driven, lay counselor-delivered intervention designed to help people
      living with HIV in resource-limited settings achieve optimal adherence. This
      pilot study examined medication adherence and key psychosocial outcomes among 55
      non-adherent South African HIV+ patients, on antiretroviral therapy (ART) for at
      least 6 months, who were randomized to receive either Masivukeni or standard of
      care (SOC) counseling for ART non-adherence. At baseline, there were no
      significant differences between the SOC and Masivukeni groups on any outcome
      variables. At post-intervention (approximately 5-6 weeks after baseline), -clinic
      based pill count adherence data available for 20 participants (10 per
      intervention arm) showed a 10 % improvement for-participants and a decrease of 8
      % for SOC participants. Masivukeni participants reported significantly more
      positive attitudes towards disclosure and medication social support, less social
      rejection, and better clinic-patient relationships than did SOC participants.
      Masivukeni shows promise to promote optimal adherence and provides preliminary
      evidence that multimedia, computer-based technology can help lay counselors offer
      better adherence counseling than standard approaches.

PMID- 25566766
TI  - Investigation of electronic structure and magnetic properties of CaCo1.86As2
      within the CPA method.
AB  - Recently in iron free arsenide compound CaCo(2)As(2) a 7(1)% of vacancies on the
      Co sites was detected (Quirinale D G et al 2013 Phys. Rev. B 88 174420). Here we
      report the investigation of electronic structure and magnetic properties of
      CaCo(1.86)As(2) within the coherent potential approximation (CPA). First, the CPA
      calculations are performed on the base of the local spin density approximation.
      Second, the possible role of Coulomb correlations is checked within the CPA
      scheme developed recently for strongly correlated systems. Then the spin-orbit
      coupling, which could be essential for Co, is also taken into account within the
      CPA calculation. The A type antiferromagnetic ground state and the value of
      magnetic moment obtained within the CPA approximation are in good agreement with
      experiment.

PMID- 25566767
TI  - Smaller but denser: postmortem changes alter the CT characteristics of subdural
      hematomas.
AB  - PURPOSE: The aim of this study was to investigate if (1) the volume of subdural
      hematomas (SDH), midline shift, and CT density of subdural hematomas are altered
      by postmortem changes and (2) if these changes are dependent on the postmortem
      interval (PMI). MATERIALS AND METHODS: Ante mortem computed tomography (AMCT) of
      the head was compared to corresponding postmortem CT (PMCT) in 19 adults with
      SDH. SDH volume, midline shift, and hematoma density were measured on both AMCT
      and PMCT and their differences assessed using Wilcoxon-Signed Rank Test.
      Spearman's Rho Test was used to assess significant correlations between the PMI
      and the alterations of SDH volume, midline shift, and hematoma density. RESULTS:
      Mean time between last AMCT and PMCT was 109 h, mean PMI was 35 h. On PMCT mean
      midline displacement was decreased by 57% (p < 0.001); mean SDH volume was
      decreased by 38% (p < 0.001); and mean hematoma density was increased by 18% (p <
      0.001) in comparison to AMCT. There was no correlation between the PMI and the
      normalization of the midline shift (p = 0.706), the reduction of SDH volume (p =
      0.366), or the increase of hematoma density (p = 0.140). CONCLUSIONS: This study
      reveals that normal postmortem changes significantly affect the extent and
      imaging characteristics of subdural hematoma and may therefore affect the
      interpretation of these findings on PMCT. Radiologists and forensic pathologists
      who use PMCT must be aware of these phenomena in order to correctly interpret
      PMCT findings in cases of subdural hemorrhages.

PMID- 25566768
TI  - Dual-energy CT behavior of heroin, cocaine, and typical adulterants.
AB  - PURPOSE: To investigate the dual-energy CT behavior of cocaine and heroin and of
      typical adulterants, and to evaluate the elemental composition of pure cocaine
      and heroin compared with cocaine and heroin in bodypacks. METHODS: Pure heroin
      and pure synthetic cocaine samples, eight different adulterants, and in each case
      ten different bodypacks containing cocaine or heroin, were imaged at 80, 100,
      120, and 140 kVp in a dual source CT system at two different degrees of
      compression. Two radiologists, blinded to the samples, measured the attenuation.
      The dual-energy index (DEI) was calculated. We performed atomic mass spectrometry
      for the elemental analysis of pure cocaine, pure heroin, and heroin and cocaine
      in bodypacks, and 140 kVp in a dual-source CT system. RESULTS: Inter- and intra
      observer agreement for attenuation measurements was good (r = 0.61-0.72; p <
      0.01). The cocaine bodypacks had a positive DEI of 0.029, while the pure drugs
      and the heroin bodypacks had a negative DEI (-0.051 to -0.027). Levamisole was
      the only substance which expressed a positive DEI of 0.011, while the remaining
      adulterants had negative DEIs ranging between -0.015 and -0.215. Atomic mass
      spectrometry revealed a concentration of tin in the cocaine bodypack that was 67
      times higher than in the pure synthetic cocaine sample. CONCLUSIONS: The
      different DEIs of bodypacks containing cocaine and heroin allow them to be
      distinguished with dual-energy CT. Although the material properties of pure
      cocaine, pure heroin, or common drug extenders do not explain the differences in
      DEI, tin contamination during illicit natural cocaine production may be a
      possible explanation.

PMID- 25566769
TI  - Two Myxobolus spp. infecting the kidney of Nile tilapia (Oreochromis niloticus)
      in the River Nile at Beni-Suef governorate, Egypt, and the associated renal
      changes.
AB  - Two Myxobolus spp. are described from the kidney of the Nile tilapia (Oreochromis
      niloticus) collected from the River Nile, Egypt. The prevalence of infection was
      61 % (47/77), with the infected fish in each case parasitized by the two
      Myxobolus species simultaneously. The infection was exhibited as free spores in
      Bowman capsules and renal glomeruli, which makes their original structures
      difficult to discern. In some cases, the infection appeared as a fibrous
      plasmodia-like structure containing degenerated developmental stages and spores
      in the interstitium. The paper identifies each species based on the morphological
      characteristics of its spores and identifies the histological impacts of
      Myxobolus infection in this species of fish.

PMID- 25566770
TI  - New host records of three juvenile nematodes in Egypt: Anisakis sp. (Type II),
      Hysterothylacium patagonense (Anisakidae), and Echinocephalus overstreeti
      (Gnathostomatidae) from the greater lizard fish Saurida undosquamis of the Red
      Sea.
AB  - Three juvenile nematode parasites were collected naturally from 90 (75 %) out of
      120 specimens of the marine greater lizard fish Saurida undosquamis captured from
      water coasts at Hurghada City along the Red Sea in Egypt during the period from
      September 2013 to April 2014. Worms were identified on the basis of light and
      scanning electron microscopy. Two of the recovered worms were isolated from the
      peritoneal cavity of the infected fish around the wall of the stomach as
      encapsulated larvae. The anisakid juvenile Anisakis sp. (Type II) was
      characterized by an anteroventrally triangular mouth, with a boring tooth; its
      postanal tail was rounded, without a terminal mucron or spine. The gnathostomatid
      Echinocephalus overstreeti was characterized by the presence of a cephalic bulb
      armed with six transverse rows of spines which were slightly more compact near
      the anterior end of bulb with maximal separation near the midbulb; the cephalic
      bulb terminated at a pseudolabia which situated dorsoventrally and reached its
      greatest width at the posterior one third of the body, The postanal tail
      terminated at a pointed mucron. The third juvenile species, Hysterothylacium
      patagonense (Anisakidae), was isolated from the intestine of the infected fish;
      they are characterized by a small-sized body with a conical tail provided by a
      nodulose apex, and the anterior end was equipped with three lips. A dorsal lip
      slightly smaller than the two subventrals left a deep postlabial groove and
      prominent lateral flanges in between, and the proximal part of each lip was
      smooth. The three described species were compared morphologically and
      morphometrically with some of the previously recorded species of the same genus.
      From this comparison, the similarity and variations between these species were
      described and concluded that the present study should be considered as a new host
      record in Egypt.

PMID- 25566771
TI  - Molecular study of Trypanosoma caninum isolates based on different genetic
      markers.
AB  - Trypanosoma caninum is a parasite recently described in dogs, whose life cycle is
      rather unknown. Here, we performed a genetic study with T. caninum samples
      obtained in different Brazilian regions. The study was based on PCR assays target
      to small and large subunit ribosomal DNA (rDNA) (18S rDNA and 24Salpha rDNA),
      cytochrome B (Cyt b), and internal transcribed spacer 1 rDNA (ITS1 rDNA)
      following by the sequence analysis. Additionally, we used primers for the
      variable regions of kinetoplast DNA (kDNA) minicircles and endonucleases
      restriction in the ITS1 rDNA amplification product. T. caninum samples displayed
      the same patterns. Tree construction confirmed the close relationship between T.
      caninum samples, regardless of the molecular target used and endonuclease
      restriction digestion revealed that all samples have the same restriction
      profile. Therefore, T. caninum seems to be a genetically homogeneous specie. In
      the kDNA assay, T. caninum possessed a different molecular size profile with
      respect to others trypanosomes, 330 and 350 bp. This study provides nucleotide
      sequences from different regions of the genome of T. caninum that certainly
      facilitate future studies.

PMID- 25566773
TI  - Temporal occurrence and community structure of helminth parasites in southern
      leopard frogs, Rana sphenocephala, from north central Oklahoma.
AB  - Currently, little information is available about the temporal recruitment of
      helminth communities in amphibian hosts. We examined the helminth community
      structure and temporal recruitment of helminth parasites in southern leopard
      frogs, Rana sphenocephala. Specifically, we were interested in how host life
      history such as habitat, age and/or size, diet, sex, and temporal variation in
      abiotic factors (precipitation and temperature) were important in determining
      monthly infection patterns of helminth populations and communities in southern
      leopard frogs. From May to September 2011, 74 southern leopard frogs were
      collected from Teal Ridge in Stillwater Payne County, OK, USA. Sixty-nine (93 %)
      of 74 frogs were infected with 1 or more helminth species. During our collecting
      period, the average monthly temperature was lowest in May and highest in July,
      and monthly precipitation was highest in May and lowest during the first week of
      September. The component community consisted of 11 species of helminth, including
      1 larval and 1 adult cestode, 2 larval and 3 adult trematodes, and 1 juvenile and
      3 adult nematodes. Of the 1790 helminths recovered, 51 % (911) were nematodes, 47
      % (842) were cestodes, and 2 % (37) were trematodes. There were significant
      differences in the total abundance and mean species richness of helminths
      acquired by skin contact or through frog diet in monthly component communities of
      southern leopard frogs. A positive correlation existed for percentage of all
      helminths acquired by skin contact and monthly precipitation (r = 0.94, P <
      0.01). Conversely, a negative correlation existed for monthly precipitation and
      percentage of helminths acquired by diet (r = -0.94, P < 0.01). Our results
      indicate that abiotic conditions such as precipitation have a major influence on
      the avenues for and constraints on the transmission of helminths with life cycles
      associated with water/moisture or terrestrial intermediate/paratenic hosts and
      are important in structuring helminth communities of amphibian hosts.

PMID- 25566772
TI  - Effect of temperature on the survival of Alaria alata mesocercariae.
AB  - Recent findings of Alaria alata mesocercariae in wild boars and other animals in
      Europe reinforced the concern about the public health risk posed by this parasite
      especially if the game meat is insufficiently heated during preparation. Cooking
      and freezing are effective methods for the inactivation of parasites in meat
      whereas refrigeration is considered as an essential part of the Good Hygiene
      Practice. Additionally, microwave dielectric heating may represent an equally
      effective tool for parasite inactivation. Therefore, isolated vital mesocercariae
      were examined with respect to their resilience against heating, refrigeration,
      freezing, and microwave heating. A. alata mesocercariae stored in Ringer's
      solution do not survive heating temperatures that exceed 60.0  degrees C.
      Similarly, exposure to microwave heating ensured an inactivation of all parasite
      developmental stages after 90 s of treatment. In contrast, the parasites'
      tolerance towards cold is far higher as the mesocercariae survived refrigeration
      temperatures (4.0 +/- 2  degrees C) in Ringer's solution for up to 13 days. An
      effective inactivation by cold is therefore only guaranteed if the infested game
      meat is frozen to a core temperature of -13.7  degrees C for a minimum of 2 h at
      least. Game meat should be handled with the same or even higher caution than meat
      of husbandry animals since wild animals may be infected with parasites or other
      zoonotic agents that are not common in livestock. It is therefore of crucial
      importance that appropriate temperature time protocols are used for the reliable
      inactivation of these zoonotic agents.

PMID- 25566775
TI  - PCDHB14- and GABRB1-like nervous system developmental genes are altered during
      early neuronal differentiation of NCCIT cells treated with ethanol.
AB  - Ethanol (EtOH) exposure during embryonic development causes dysfunction of the
      central nervous system (CNS). Here, we examined the effects of chronic EtOH on
      gene expression during early stages of neuronal differentiation. Human embryonic
      carcinoma (NCCIT) cells were differentiated into neuronal precursors/lineages in
      the presence or absence of EtOH and folic acid. Gene expression profiling and
      pathway analysis demonstrated that EtOH deregulates many genes and pathways that
      are involved in early brain development. EtOH exposure downregulated several
      important genes, such as PCDHB14, GABRB1, CTNND2, NAV3, RALDH1, and OPN5, which
      are involved in CNS development, synapse assembly, synaptic transmission, and
      neurotransmitter receptor activity. GeneGo pathway analysis revealed that the
      deregulated genes mapped to disease pathways that were relevant to fetal alcohol
      spectrum disorders (FASD, such as neurotic disorders, epilepsy, and alcohol
      related disorders). In conclusion, these findings suggest that the impairment of
      the neurological system or suboptimal synapse formation resulting from EtOH
      exposure could underlie the neurodevelopmental disorders in individuals with
      FASD. 

PMID- 25566777
TI  - Flu is now widespread in 43 US states, CDC reports.

PMID- 25566774
TI  - Expression, purification, and biochemical characterization of recombinant DNA
      polymerase beta of the Trypanosoma cruzi TcI lineage: requirement of additional
      factors and detection of phosphorylation of the native form.
AB  - Chagas disease, caused by the protozoan Trypanosoma cruzi, is a major parasitic
      disease that affects millions of people in America. However, despite the high
      impact of this disease on human health, no effective and safe treatment has been
      found that eliminates the infecting parasite from human patients. Among the
      possible chemotherapeutic targets that could be considered for study in T. cruzi
      are the DNA polymerases, in particular DNA polymerase beta (polbeta), which
      previous studies have shown to be involved in kinetoplast DNA replication and
      repair. In this paper, we describe the expression, purification, and biochemical
      characterization of the Miranda clone polbeta, corresponding to lineage T. cruzi
      I (TcI). The recombinant enzyme purified to homogeneity displayed specific
      activity in the range described for a highly purified mammalian polbeta. However,
      the trypanosome enzyme exhibited important differences in biochemical properties
      compared to the mammalian enzymes, specifically an almost absolute dependency on
      KCl, high sensitivity to N-ethylmaleimide (NEM), and low sensitivity to ddTTP.
      Immuno-affinity purification of T. cruzi polymerase beta (Tcpolbeta) from
      epimastigote extracts showed that the native enzyme was phosphorylated. In
      addition, it was demonstrated that Tcpolbeta interacts with some proteins in a
      group of about 15 proteins which are required to repair 1-6 bases of gaps of a
      double strand damaged DNA. It is possible that these proteins form part of a DNA
      repair complex, analogous to that described in mammals and some trypanosomatids. 

PMID- 25566778
TI  - Preface. Patenting and related patenting activities.

PMID- 25566776
TI  - Prevalence of Cytauxzoon felis infection in healthy cats from enzootic areas in
      Arkansas, Missouri, and Oklahoma.
AB  - BACKGROUND: Infection with Cytauxzoon felis in domestic cats can cause fever,
      lethargy, depression, inappetence, icterus, and often death. With a high
      mortality rate, cytauxzoonosis was historically considered a fatal disease.
      Within the last 15 years, cats with or without treatment have been recognized as
      chronically infected survivors of C. felis infection. Our objective was to
      determine the prevalence of C. felis in healthy domestic cats from Arkansas,
      Missouri, and Oklahoma. METHODS: Infection with C. felis was determined using DNA
      extracted from anticoagulated whole blood and PCR amplification using C. felis
      specific primers. Chi-square, Fisher's exact tests, and odds ratios were used to
      compare proportions of cats infected with C. felis. RESULTS: Blood samples were
      collected from 902 healthy domestic cats between October 2008 and April 2012. DNA
      from Cytauxzoon felis was detected in 56 of 902 (6.2%; 95% confidence interval,
      4.7-7.9) samples. The highest prevalence of C. felis infection (15.5%; 10.3-21.7)
      was observed in cats from Arkansas, followed by cats from Missouri (12.9%; 6.1
      24.0), and cats from Oklahoma (3.4%; 2.2-5.1). Cats sampled in Arkansas and
      Missouri were 5.1 and 4.2, respectively, times more likely to be chronically
      infected with C. felis than cats from Oklahoma. CONCLUSIONS: Infection with C.
      felis is common in domestic cats through Arkansas, Missouri, and Oklahoma. The
      high prevalence of C. felis reported herein suggests that infected domestic cats
      are likely reservoirs of infection for naive felines. The high prevalence of C.
      felis substantiates the importance for the use of approved acaricides on cats to
      prevent cytauxzoonosis.

PMID- 25566779
TI  - Editorial: special issue: genetically modified foods: are they really better?

PMID- 25566781
TI  - Patterns and Predictors of First-Line Antiretroviral Therapy Modification in HIV
      1-Infected Adults in a Large Urban Outpatient Cohort in Nigeria.
AB  - OBJECTIVE: We described the magnitude, type, and factors associated with first
      line antiretroviral therapy (ART) modification in HIV-1-infected adults on ART in
      Jos, Nigeria. METHOD: Data on 6309 patients initiated on first-line ART between
      January 2004 and December 2006 were analyzed retrospectively. Factors predictive
      of modification to initial ART were assessed by chi-square and multivariable
      logistic regression analysis. RESULTS: Overall, 5212 (83%) included patients
      incurred a modification (73.3% drug substitution and 9.7% drug switch) to their
      initial first-line ARV regimen during a median (interquartile range) follow-up
      period of 7 (3-8) years. Drug substitutions of zidovudine (ZDV) were less likely
      than of tenofovir (TDF; adjusted odd ratio [AOR] 0.6; 95% confidence interval
      [CI]: 0.51-0.71), and Drug substitutions of efavirenz (EFV) were more likely than
      of nevirapine (NVP)-containing (AOR 1.82; 95% CI: 1.42-2.33) regimens. Predictors
      of switch to second-line regimen include older age (AOR 2.05; 95% CI: 1.68-2.51),
      CD4 count<=100 cells/mm3 (AOR 1.89; 95% CI: 1.49-2.37), EFV compared to NVP (AOR
      1.38; 95% CI: 1.02-1.88), and drug toxicity (AOR 1.90; 95% CI: 1.48-2.43).
      CONCLUSION: Modification to initial ART was common in this study. Further
      evaluation of the contribution of guideline changes on regimen modification and
      treatment outcomes is recommended.

PMID- 25566782
TI  - The Impact of Flavor Descriptors on Nonsmoking Teens' and Adult Smokers' Interest
      in Electronic Cigarettes.
AB  - INTRODUCTION: Smokers switching completely from combustible cigarettes to
      electronic cigarettes (e-cigarettes) are likely to reduce health risk, suggesting
      that e-cigarettes should be made appealing to adult smokers. However, uptake of e
      cigarettes by nonsmoking teens would add risk without benefit and should be
      avoided. Although e-cigarette flavors may appeal to adult smokers, the concern is
      that flavors might attract nonsmoking teens. METHODS: Nonsmoking teens (n = 216,
      ages 13-17, no tobacco in past 6 months) and adult smokers (n = 432, ages 19-80,
      smoking 3+ years; could have used e-cigarettes) were recruited from an Internet
      research panel. In assessments completed online (May 22, 2014 to June 13, 2014),
      participants indicated their interest (0-10 scale) in e-cigarettes paired with
      various flavor descriptors. These were mixed (order balanced) with similar flavor
      offerings for ice cream and bottled water to mask the focus on e-cigarettes and
      validate the assessment. Mixed models contrasted interest between teens and
      adults and among adults by e-cigarette history. RESULTS: Nonsmoking teens'
      interest in e-cigarettes was very low (mean = 0.41 +/- 0.14 [SE] on 0-10 scale).
      Adult smokers' interest (1.73 +/- 0.10), while modest, was significantly higher
      overall (p < .0001) and for each flavor (most p values < .0001). Teen interest
      did not vary by flavor (p = .75), but adult interest did (p < .0001). Past-30-day
      adult e-cigarette users had the greatest interest in e-cigarettes, and their
      interest was most affected by flavor. Adults who never tried e-cigarettes had the
      lowest interest, yet still higher than nonsmoking teens' interest (p < .0001).
      CONCLUSION: The e-cigarette flavors tested appealed more to adult smokers than to
      nonsmoking teens, but interest in flavors was low for both groups.

PMID- 25566784
TI  - Intensive treatment for type 1 diabetes is associated with lower risk of death.

PMID- 25566783
TI  - Reducing disability in community-dwelling frail older people: cost-effectiveness
      study alongside a cluster randomised controlled trial.
AB  - BACKGROUND: although proactive primary care, including early detection and
      treatment of community-dwelling frail older people, is a part of the national
      healthcare policy in several countries, little is known about its cost
      effectiveness. OBJECTIVE: to evaluate the cost-effectiveness of a proactive
      primary care approach in community-dwelling frail older people. DESIGN AND
      SETTING: embedded in a cluster randomised trial among 12 Dutch general
      practitioner practices, an economic evaluation was performed from a societal
      perspective with a time horizon of 24 months. METHOD: frail older people in the
      intervention group received an in-home assessment and interdisciplinary care
      based on a tailor-made treatment plan and regular evaluation and follow-up.
      Practices in the control group delivered usual care. The primary outcome for the
      cost-effectiveness and cost-utility analysis was disability and health-related
      quality of life, respectively. RESULTS: multilevel analyses among 346 frail older
      people showed no significant differences between the groups regarding disability
      and health-related quality of life at 24 months. People in the intervention group
      used, as expected, more primary care services, but there was no decline in more
      expensive hospital and long-term care. Total costs over 24 months tended to be
      higher in the intervention group than in the control group (?26,503 versus
      ?20,550, P = 0.08). CONCLUSIONS: the intervention under study led to an increase
      in healthcare utilisation and related costs without providing any beneficial
      effects. This study adds to the scarce amount of evidence of the cost
      effectiveness of proactive primary care in community-dwelling frail older people.
      TRIAL REGISTRATION: Current Controlled Trials, ISRCTN 31954692.

PMID- 25566785
TI  - The success factors of scaling-up Estonian sexual and reproductive health youth
      clinic network--from a grassroots initiative to a national programme 1991-2013.
AB  - BACKGROUND: A growing number of middle-income countries are scaling up youth
      friendly sexual and reproductive health pilot projects to national level
      programmes. Yet, there are few case studies on successful national level scale-up
      of such programmes. Estonia is an excellent example of scale-up of a small
      grassroots adolescent sexual and reproductive health initiative to a national
      programme, which most likely contributed to improved adolescent sexual and
      reproductive health outcomes. This study; (1) documents the scale-up process of
      the Estonian youth clinic network 1991-2013, and (2) analyses factors that
      contributed to the successful scale-up. This research provides policy makers and
      programme managers with new insights to success factors of the scale-up, that can
      be used to support planning, implementation and scale-up of adolescent sexual and
      reproductive health programmes in other countries. METHODS: Information on the
      scale-up process and success factors were collected by conducting a literature
      review and interviewing key stakeholders. The findings were analysed using the
      WHO-ExpandNet framework, which provides a step-by-step process approach for
      design, implementation and assessment of the results of scaling-up health
      innovations. RESULTS: The scale-up was divided into two main phases: (1) planning
      the scale-up strategy 1991-1995 and (2) managing the scaling-up 1996-2013. The
      planning phase analysed innovation, user organizations (youth clinics),
      environment and resource team (a national NGO and international assistance). The
      managing phase examines strategic choices, advocacy, organization, resource
      mobilization, monitoring and evaluation, strategic planning and management of the
      scale-up. CONCLUSIONS: The main factors that contributed to the successful scale
      up in Estonia were: (1) favourable social and political climate, (2) clear
      demonstrated need for the adolescent services, (3) a national professional
      organization that advocated, coordinated and represented the youth clinics, (4)
      enthusiasm and dedication of personnel, (5) acceptance by user organizations and
      (6) sustainable funding through the national health insurance system. Finally,
      the measurement and recognition of the remarkable improvement of adolescent SRH
      outcomes in Estonia would not have been possible without development of good
      reporting and monitoring systems, and many studies and international
      publications.

PMID- 25566787
TI  - Effect of hydration repulsion on nanoparticle agglomeration evaluated via a
      constant number Monte-Carlo simulation.
AB  - The effect of hydration repulsion on the agglomeration of nanoparticles in
      aqueous suspensions was investigated via the description of agglomeration by the
      Smoluchowski coagulation equation using constant number Monte-Carlo simulation
      making use of the classical DLVO theory extended to include the hydration
      repulsion energy. Evaluation of experimental DLS measurements for TiO2, CeO2,
      SiO2, and alpha-Fe2O3 (hematite) at high IS (up to 900 mM) or low |zeta
      potential| (>=1.35 mV) demonstrated that hydration repulsion energy can be above
      electrostatic repulsion energy such that the increased overall repulsion energy
      can significantly lower the agglomerate diameter relative to the classical DLVO
      prediction. While the classical DLVO theory, which is reasonably applicable for
      agglomeration of NPs of high |zeta-potential| (~>35 mV) in suspensions of low IS
      (~<1 mM), it can overpredict agglomerate sizes by up to a factor of 5 at high IS
      or low |zeta-potential|. Given the potential important role of hydration
      repulsion over a range of relevant conditions, there is merit in quantifying this
      repulsion energy over a wide range of conditions as part of overall
      characterization of NP suspensions. Such information would be of relevance to
      improved understanding of NP agglomeration in aqueous suspensions and its
      correlation with NP physicochemical and solution properties. 

PMID- 25566788
TI  - The unknown risks of youth rugby.

PMID- 25566786
TI  - Autochthonous transmission of Chagas disease in Rio de Janeiro State, Brazil: a
      clinical and eco-epidemiological study.
AB  - BACKGROUND: After the control of the main modes of Chagas disease (CD)
      transmission in most endemic countries, it is important to identify the
      participation of native sylvatic vectors in CD transmission. Although CD is not
      considered endemic in Rio de Janeiro State (RJ), Brazil, we identified patients
      with CD born in RJ and investigated the possible autochthonous transmission in
      the state. METHODS: Patients born in RJ and followed in our institution between
      1986 and 2011 were retrospectively analyzed. The cases identified as
      autochthonous transmission were submitted to epidemiological, clinical,
      serological, parasitological and molecular studies. Sectional field study with
      serological survey, research of sylvatic reservoirs and vectors was conducted in
      rural areas where patients were born. RESULTS: Among 1963 patients, 69 (3.5%)
      were born in RJ. From these, 15 (21.7%) were considered to have acquired the
      infection by autochthonous transmission. Cardiac form was the commonest form of
      presentation (60%). In rural areas in RJ northern region, sylvatic cycles of
      Trypanosoma cruzi and domestic invasion by Triatoma vitticeps were identified,
      and CD prevalence among inhabitants was 0.74%.TcI genotype was identified in
      sylvatic reservoirs and vectors. The genotype (mixed infection TcI/TcVI) could be
      identified in one of the autochthonous cases. CONCLUSIONS: The autochthonous
      vectorial transmission of CD occurs in RJ, probably due to wild cycles of T.
      cruzi and sylvatic vectors, such as T. vitticeps. Therefore, the health
      authorities should evaluate if RJ should be included in the original endemic area
      of CD and CD should be included in the diagnostic work out of cardiomyopathy of
      patients born in RJ. Moreover, control and educational measures should be put
      into place in the risk areas.

PMID- 25566790
TI  - How the government intervention affects the distribution of physicians in Turkey
      between 1965 and 2000.
AB  - INTRODUCTION: One of the main weaknesses of the health system in Turkey is the
      uneven distribution of physicians. The diversity among geographical districts was
      huge in the beginning of the 1960s. After the 1980s, the implementation of a two
      year compulsory service for newly graduated physicians is an interesting and
      specific experience for all countries. The aim of this study is to analyse the
      distribution of physicians, GPs and specialists between the years 1965-2000 and
      the efficiency of the strict 15 year government intervention (1981-1995).
      METHODS: The data used in this study includes the published data by the Ministry
      of Health and The State Institute of Statistics between the years 1965-2000.
      Covering 35 years for total physicians, GPs and specialists, Gini coefficients
      are calculated so as to observe the change in the distribution. In order to
      measure the efficiency of government intervention, Gini index belonging to the
      previous 15 years (first period-1965 to 1980) and the last 15 years (second
      period) of 1981 when the compulsory service was enacted is also analysed
      including the statistical tests. RESULTS: In 1965, the Gini for total physician
      is quite high (0.47), and in 2000 it decreases considerably (0.20). In 1965, the
      Gini for GPs and the Gini for specialists is 0.44 and 0.52, respectively and in
      2000 these values decrease to 0.13 and 0.28, respectively. It is observed that,
      with this government intervention, the level of diversity has decreased
      dramatically up to 2000. Regarding to regression, the rate of decrease in Gini
      index in the second period is higher for the GPs than that of the specialists.
      CONCLUSION: The inequalities in the distribution between GPs and specialists are
      significantly different; inequality of specialist distribution is higher than the
      GP. The improvement of the inequality in the physician distribution produced by
      the market mechanism shows a long period when it is left to its own devices. It
      is seen that the compulsory service policy is efficient since the physician
      distribution has improved significantly. The government intervention provides a
      faster improvement in the GP distribution.

PMID- 25566789
TI  - Rules of parotid gland dose variations and shift during intensity modulated
      radiation therapy for nasopharyngeal carcinoma.
AB  - BACKGROUND: To determine the position and dose delivery changes rules of parotid
      gland (PG) during the course of intensity modulated radiation therapy (IMRT) in
      nasopharyngeal carcinoma patients (NPC). MATERIALS AND METHODS: One hundred and
      forty one competed tomography (CT) images from 47 NPC patients (three images for
      each patient were acquired before treatment, at the 15th and 25th fraction during
      the treatment) who underwent radical IMRT were selected for this study. A total
      of 70-76Gy at 2.12-2.3 Gy/fraction/d was given to the GTVnx in 33 fractions. The
      distances between the lateral/medial aspects of PG and midline (DLM and DMM) at
      the level of odontoid process were measured. The dose differences between plan
      and actual delivery were calculated. RESULTS: The volume reductions of PGs
      between fractions 15 and 25 were larger than those in the first 15 fractions
      (4.68 +/- 3.23 cc vs. 2.46 +/- 4.55 cc for the right PG and 5.96 +/- 2.99 cc vs.
      2.06 +/- 2.99 cc for the left PG). However, the percentage of gland volume
      receiving >= 30 Gy (V30) of bilateral PGs decreased more significantly in the
      first 15 fractions than that between fractions 15 and 25 (5.61 +/- 16.04% vs.
      1.14 +/- 21.54% for the right PG and 6.87 +/- 15.58% vs. 0.81 +/- 15.94% for the
      left PG). The gross tumor volume of the nasopharynx (GTVnx) decreased more
      significantly in the first 15 fractions than that between the 15th and 25th
      fraction (8.23 +/- 13.61 cc vs. 3.30 +/- 8.09 cc). The DMM of ipsilateral PGs
      reduced in the first 15 fractions (0.80 +/- 2.96 mm) but increased between
      fraction 15 and 25 (-2.19 +/- 3.96 mm). While ipsilateral PG shifted into target
      volume but shifted out target volume between fraction 15 and 25. Parotid glands
      V30 was correlated with GTVnx, GTVnx reduction and DMM reduction (p<0.01).
      CONCLUSION: Our results indicate that the reduction of GTVnx leads to the
      positional change of the parotid gland, which results in more significant dose
      change of the parotid gland in the first 15 fractions than that between fraction
      15 and 25.

PMID- 25566791
TI  - Differences in the Molecular Species of CA125 Across the Phases of the Menstrual
      Cycle.
AB  - BACKGROUND: CA125, a tumor-associated antigen, is primarily used to monitor
      epithelial ovarian cancer. There is evidence that different species of CA125
      exist; however, it is not known if any of these species are present in healthy
      women during the menstrual cycle and if they are associated with serum
      concentrations of CA125. The purpose of this study was to determine if the
      molecular species of CA125 differ across the three phases of the menstrual cycle
      in healthy women. METHODS: Healthy, Caucasian women between the ages of 18 and 39
      were enrolled using strict criteria to exclude factors known to contribute to
      CA125 fluctuations. Menstrual cycle regularity was determined using calendars
      maintained by participants for 3 months. After cycle regularity was established,
      blood was drawn at three time points for Western blot analysis. RESULTS: Western
      blot analysis yielded 17 distinct profiles (i.e., patterns of species) of CA125,
      with 80% of the sample exhibiting 5 common profiles. No differences in
      demographic characteristics and serum CA125 values were found among the various
      CA125 profiles. CONCLUSIONS: Different molecular species of CA125 exist in
      healthy women with regular menstrual cycles. These data provide evidence that
      CA125 is not a homogeneous molecular species. Future research should evaluate the
      molecular composition and the clinical importance of these species.

PMID- 25566792
TI  - The -93T/G LPL Promoter Polymorphism Is Associated With Lower Third-Trimester
      Triglycerides in Pregnant African American Women.
AB  - BACKGROUND: Hypertriglyceridemia is a risk factor for cardiovascular disease and
      several pregnancy complications. Lipoprotein lipase (LPL) genetic variation
      modulates nonpregnancy plasma triglycerides, but its effects during pregnancy are
      unknown. The G allele of the LPL -93T/G promoter polymorphism is 16-23 times more
      prevalent in Blacks than in Whites, contributing to lower triglycerides in
      nonpregnant African Americans by increasing LPL expression. PURPOSE: This study
      investigated whether the triglyceride-lowering effect of -93G is observed in
      African Americans during pregnancy. METHODS: Genotyping was performed on 124
      African American women with uncomplicated pregnancies for common functional LPL
      polymorphisms/mutations (-93T/G, D9N, N291S, and S447X). Third-trimester plasma
      triglyceride, high- and low-density lipoprotein cholesterol, apolipoprotein B,
      and free fatty acid concentrations were measured with colorimetric assays.
      Clinical characteristics and lipid values were compared across the -93T/G
      genotypes. RESULTS: Triglycerides were significantly lower in women with the 
      93GG compared to the -93TT genotype, both with (n = 124, p = .02) and without (n
      = 108, p = .03) inclusion of participants with other LPL variant alleles.
      Triglyceride differences persisted after adjustment for prepregnancy body mass
      index, gestational age at delivery, and smoking. There were no significant
      differences in the other lipids or apolipoprotein B by -93T/G genotype.
      CONCLUSIONS: Despite the considerable metabolic changes accompanying pregnancy,
      the triglyceride-lowering effect associated with the -93GG LPL genotype in
      African Americans persists during late pregnancy. The -93GG genotype might
      protect against pregnancy complications stemming from hypertriglyceridemia, but
      the overall increased risk of pregnancy complications in African American women
      points to complex, multifactorial relationships among risk factors, race, and
      adverse pregnancy outcomes.

PMID- 25566793
TI  - Comparison of T7E1 and surveyor mismatch cleavage assays to detect mutations
      triggered by engineered nucleases.
AB  - Genome editing using engineered nucleases is used for targeted mutagenesis. But
      because genome editing does not target all loci with similar efficiencies, the
      mutation hit-rate at a given locus needs to be evaluated. The analysis of mutants
      obtained using engineered nucleases requires specific methods for mutation
      detection, and the enzyme mismatch cleavage method is used commonly for this
      purpose. This method uses enzymes that cleave heteroduplex DNA at mismatches and
      extrahelical loops formed by single or multiple nucleotides. Bacteriophage
      resolvases and single-stranded nucleases are used commonly in the assay but have
      not been compared side-by-side on mutations obtained by engineered nucleases. We
      present the first comparison of the sensitivity of T7E1 and Surveyor EMC assays
      on deletions and point mutations obtained by zinc finger nuclease targeting in
      frog embryos. We report the mutation detection limits and efficiencies of T7E1
      and Surveyor. In addition, we find that T7E1 outperforms the Surveyor nuclease in
      terms of sensitivity with deletion substrates, whereas Surveyor is better for
      detecting single nucleotide changes. We conclude that T7E1 is the preferred
      enzyme to scan mutations triggered by engineered nucleases. 

PMID- 25566795
TI  - Studying the neurobiology of human social interaction: Making the case for
      ecological validity.
AB  - With this commentary we make the case for an increased focus on the ecological
      validity of the measures used to assess aspects of human social functioning.
      Impairments in social functioning are seen in many types of psychopathology,
      negatively affecting the lives of psychiatric patients and those around them. Yet
      the neurobiology underlying abnormal social interaction remains unclear. As an
      example of human social neuroscience research with relevance to biological
      psychiatry and clinical psychopharmacology, this commentary discusses published
      experimental studies involving manipulation of the human brain serotonin system
      that included assessments of social behavior. To date, these studies have mostly
      been laboratory-based and included computer tasks, observations by others, or
      single-administration self-report measures. Most laboratory measures used so far
      inform about the role of serotonin in aspects of social interaction, but the
      relevance for real-life interaction is often unclear. Few studies have used
      naturalistic assessments in real life. We suggest several laboratory methods with
      high ecological validity as well as ecological momentary assessment, which
      involves intensive repeated measures in naturalistic settings. In sum, this
      commentary intends to stimulate experimental research on the neurobiology of
      human social interaction as it occurs in real life. 

PMID- 25566794
TI  - Genetic markers for western corn rootworm resistance to Bt toxin.
AB  - Western corn rootworm (WCR) is a major maize (Zea mays L.) pest leading to annual
      economic losses of more than 1 billion dollars in the United States. Transgenic
      maize expressing insecticidal toxins derived from the bacterium Bacillus
      thuringiensis (Bt) are widely used for the management of WCR. However,
      cultivation of Bt-expressing maize places intense selection pressure on pest
      populations to evolve resistance. Instances of resistance to Bt toxins have been
      reported in WCR. Developing genetic markers for resistance will help in
      characterizing the extent of existing issues, predicting where future field
      failures may occur, improving insect resistance management strategies, and in
      designing and sustainably implementing forthcoming WCR control products. Here, we
      discover and validate genetic markers in WCR that are associated with resistance
      to the Cry3Bb1 Bt toxin. A field-derived WCR population known to be resistant to
      the Cry3Bb1 Bt toxin was used to generate a genetic map and to identify a genomic
      region associated with Cry3Bb1 resistance. Our results indicate that resistance
      is inherited in a nearly recessive manner and associated with a single autosomal
      linkage group. Markers tightly linked with resistance were validated using WCR
      populations collected from Cry3Bb1 maize fields showing significant WCR damage
      from across the US Corn Belt. Two markers were found to be correlated with both
      diet (R2 = 0.14) and plant (R2 = 0.23) bioassays for resistance. These results
      will assist in assessing resistance risk for different WCR populations, and can
      be used to improve insect resistance management strategies.

PMID- 25566796
TI  - Thinking small: towards microRNA-based therapeutics for anxiety disorders.
AB  - INTRODUCTION: Anxiety disorders are the most frequently diagnosed psychiatric
      conditions, negatively affecting quality of life and creating a significant
      economic burden. These complex disorders are extremely difficult to treat, and
      there is a great need for novel therapeutics with greater efficacy and minimal
      adverse side effects. AREAS COVERED: In this review, the authors describe the
      role that microribonucleic acids (microRNA or miRNA) play in the development of
      anxiety disorders and their potential to serve as biomarkers of disease as well
      as targets for pharmacological treatment. Furthermore, the authors discuss the
      current state of miRNA research, including both preclinical and clinical studies
      of anxiety disorders. EXPERT OPINION: There is mounting evidence that circulating
      miRNA may serve as biomarkers of disease and play a role in the development of
      disease, including psychiatric conditions such as anxiety disorders. Great
      strides have been made in cancer research, with miRNA-based therapies already in
      use in clinical studies. However, the use of miRNA for the treatment of
      neurological disorders, and psychiatric disorders in particular, is still in its
      nascent stage. The development of safe compounds that are able to cross the blood
      brain barrier and target specific cell populations, which are relevant to anxiety
      related neurocircuitry, is paramount for the emergence of novel, efficacious
      miRNA-based therapies in clinical settings.

PMID- 25566797
TI  - Genetically modified crops and small-scale farmers: main opportunities and
      challenges.
AB  - Although some important features of genetically modified (GM) crops such as
      insect resistance, herbicide tolerance, and drought tolerance might seem to be
      beneficial for small-scale farmers, the adoption of GM technology by smallholders
      is still slight. Identifying pros and cons of using this technology is important
      to understand the impacts of GM crops on these farmers. This article reviews the
      main opportunities and challenges of GM crops for small-scale farmers in
      developing countries. The most significant advantages of GM crops include being
      independent to farm size, environment protection, improvement of occupational
      health issues, and the potential of bio-fortified crops to reduce malnutrition.
      Challenges faced by small-scale farmers for adoption of GM crops comprise
      availability and accessibility of GM crop seeds, seed dissemination and price,
      and the lack of adequate information. In addition, R&D and production costs in
      using GM crops make it difficult for these farmers to adopt the use of these
      crops. Moreover, intellectual property right regulations may deprive resource
      poor farmers from the advantages of GM technology. Finally, concerns on socio
      economic and environment safety issues are also addressed in this paper. 

PMID- 25566798
TI  - Chemical constituents, anticancer, antimicrobial and antioxidant activities of
      essential oil from Anaphalis lacteal grown in Qinghai-Tibet Plateau.
AB  - The chemical constituent of the essential oil from Anaphalis lacteal was
      determined; 31 compounds, representing 93.91% of the total oil, were identified
      by gas chromatography-mass spectrometry analysis. Three Gram-positive bacteria
      species, three Gram-negative bacteria species and four fungi were used to
      determine antimicrobial activity; the results revealed that the essential oil had
      a remarkable antimicrobial effect against bacteria and a susceptive effect
      against fungus. The oil also possessed more efficient free-radical scavenging
      activities than butylated hydroxytoluene (BHT) with 50% inhibitory concentration
      (IC50) value 31 MUg/mL (40 MUg/mL for BHT). MTT assay illustrated that the oil
      expressed certain effect in inhibiting the growth of HeLa and Hep-6 cancer cells.

PMID- 25566799
TI  - No need for an initial test dose of meropenem or ertapenem in patients reporting
      anaphylactic reactions to penicillins.

PMID- 25566800
TI  - Synthetic biology devices and circuits for RNA-based 'smart vaccines': a
      propositional review.
AB  - Nucleic acid vaccines have been gaining attention as an alternative to the
      standard attenuated pathogen or protein based vaccine. However, an unrealized
      advantage of using such DNA or RNA based vaccination modalities is the ability to
      program within these nucleic acids regulatory devices that would provide an
      immunologist with the power to control the production of antigens and adjuvants
      in a desirable manner by administering small molecule drugs as chemical triggers.
      Advances in synthetic biology have resulted in the creation of highly predictable
      and modular genetic parts and devices that can be composed into synthetic gene
      circuits with complex behaviors. With the recent advent of modified RNA gene
      delivery methods and developments in the RNA replicon platform, we foresee a
      future in which mammalian synthetic biologists will create genetic circuits
      encoded exclusively on RNA. Here, we review the current repertoire of devices
      used in RNA synthetic biology and propose how programmable 'smart vaccines' will
      revolutionize the field of RNA vaccination. 

PMID- 25566801
TI  - Real-time photothermal imaging and response in pulsed dye laser treatment for
      port wine stain patients.
AB  - BACKGROUND: This study was performed to assess the photothermal response of
      highly focused laser energy using infrared thermal imaging instrument to detect
      and assess the actual temperature distribution during flash lamp pumped pulsed
      dye laser (FLPPDL) treatment for port wine stain (PWS) patients and avoiding its
      complications. METHODS: A retrospective review of 40 patients with PWS birthmark
      treated with FLPPDL (l = 585 nm, tp = 1500 ms, 7 mm spot) was conducted over a 2
      year period. Subjects' ages ranged between 28 and 46 years (mean 29 years); there
      were 24 females and 16 males. Twenty patients received non-cooling laser
      treatment (NC-LT) using light dosages of 5-12 J/cm 2 . Another 20 patients
      received cryogen spray cooling laser treatment (CSC-LT) using light dosages of 5
      12 J/cm 2 . A real-time infrared thermal imaging and the thermal wave equation
      were used for assessment. The results of temperature distributions related to the
      energy change were analyzed. RESULTS: Proper temperature measurement using
      infrared thermal imaging instrument and thermal wave equation in non-cooled PWS
      patients showed that the energy density of pulsed dye laser (PDL) higher than 7
      J/cm 2 can reach >44 degrees C and result in burn injury. However, when energy
      densities beyond 10 J/cm 2 were administered, along with using CSC, thermal
      damage was could still be minimized without the risk of damage to the treated
      area. CONCLUSION: Using infrared thermal imaging instrument and thermal wave
      equation, we can predict the skin temperature distribution in FLPPDL for PWS
      patients during the treatment. In conjunction with CSC, the complications can be
      minimized.

PMID- 25566802
TI  - APOBEC3B: pathological consequences of an innate immune DNA mutator.
AB  - Cancer is a disease that results from alterations in the cellular genome. Several
      recent studies have identified mutational signatures that implicate a variety of
      mutagenic processes in cancer, a major one of which is explained by the enzymatic
      activity of the DNA cytosine deaminase, APOBEC3B. As a deaminase, APOBEC3B
      converts cytosines to uracils in single-stranded DNA. Failure to properly repair
      these uracil lesions can result in a diverse array of mutations. For instance,
      DNA uracils can template the insertion of complementary adenines leading to C-to
      T transition mutations. DNA uracils can also be converted into abasic sites that,
      depending upon the DNA polymerase recruited to bypass this lesion in the template
      strand, can lead to adenine insertion and C-to-T mutations as well as cytosine
      insertion and C-to-G transversion mutations. Finally, DNA uracils can also be
      converted into DNA breaks that may precipitate some types of larger chromosomal
      aberrations observed in cancer. These studies cumulatively demonstrate that
      APOBEC3B is a major source of genetic heterogeneity in several human cancers and,
      as such, this enzyme may prove to be a critical diagnostic and therapeutic
      target. 

PMID- 25566803
TI  - Effects of proximal grooves and abutment height on the resistance of resin
      cemented crowns in teeth with inadequate resistance: An in vitro study.
AB  - BACKGROUND: The resistance form is a key factor for a successful crown
      fabrication. This in vitro study evaluates the effects of proximal grooves and
      abutment height on the resistance of single cast crowns in molars with inadequate
      resistance. METHODS: Sixty extracted human molars were prepared to possess 20
      degrees  of total occlusal convergence for single crown fabrication. All of the
      prepared teeth were divided into six groups and prepared according to three axial
      heights (2, 3, and 4 mm) with or without preparing a pair of proximal grooves.
      Alloy metal copings of 5% titanium were casted and cemented. A self-adhesive
      modified-resin cement was used for cementation. A lateral dislodgement test was
      performed with an increasing external force applied at a 45 degrees  angulation
      on a universal testing machine. The force required to dislodge the crown from the
      tooth or to break the core was recorded. RESULTS: Proximal grooves increased the
      dislodgement resistance in groups with an abutment height of 4 mm, whereas adding
      grooves made no significant differences in resistance in groups with abutment
      heights of 2 and 3 mm. The 2 mm groups exhibited worse performance than the other
      groups, whether they had proximal grooves or not. CONCLUSION: An abutment height
      of 3 mm provided adequate resistance for single cast crowns when self-adhesive
      modified-resin cement was used. Preparing a pair of proximal grooves on abutments
      shorter than 4 mm had no significant influence on the resistance.

PMID- 25566806
TI  - Plant alkaloid chelerythrine induced aggregation of human telomere sequence--a
      unique mode of association between a small molecule and a quadruplex.
AB  - Small molecules that interact with G-quadruplex structures formed by the human
      telomeric region and stabilize them have the potential to evolve as anticancer
      therapeutic agents. Herein we report the interaction of a putative anticancer
      agent from a plant source, chelerythrine, with the human telomeric DNA sequence.
      It has telomerase inhibitory potential as demonstrated from telomerase repeat
      amplification assay in cancer cell line extract. We have attributed this to the
      quadruplex binding potential of the molecule and characterized the molecular
      details of the interaction by means of optical spectroscopy such as absorbance
      and circular dichroism and calorimetric techniques such as isothermal titration
      calorimetry and differential scanning calorimetry. The results show that
      chelerythrine binds with micromolar dissociation constant and 2:1 binding
      stoichiometry to the human telomeric DNA sequence. Chelerythrine association
      stabilizes the G-quadruplex. Nuclear magnetic resonance spectroscopy ((1)H and
      (31)P) shows that chelerythrine binds to both G-quartet and phosphate backbone of
      the quadruplex leading to quadruplex aggregation. Molecular dynamics simulation
      studies support the above inferences and provide further insight into the
      mechanism of ligand binding. The specificity toward quartet binding for
      chelerythrine is higher compared to that of groove binding. MM-PBSA calculation
      mines out the energy penalty for quartet binding to be -4.7 kcal/mol, whereas
      that of the groove binding is -1.7 kcal/mol. We propose that the first
      chelerythrine molecule binds to the quartet followed by a second molecule which
      binds to the groove. This second molecule might bring about aggregation of the
      quadruplex structure which is evident from the results of nuclear magnetic
      resonance. 

PMID- 25566807
TI  - Characteristics and clinical management of patients admitted to cholera wards in
      a regional referral hospital during the 2012 epidemic in Sierra Leone.
AB  - BACKGROUND AND OBJECTIVES: In 2012, Sierra Leone suffered a nationwide cholera
      epidemic which affected the capital Freetown and also the provinces. This study
      aims to describe the characteristics and clinical management of patients admitted
      to cholera isolation wards of the main referral hospital in the Northern Province
      and compare management with standard guidelines. DESIGN: All available clinical
      records of patients from the cholera isolation wards were reviewed
      retrospectively. There was no active case finding. The following data were
      collected from the clinical records after patients had left the ward: date of
      admission, demographics, symptoms, dehydration status, diagnoses, tests and
      treatments given, length of stay, and outcomes. RESULTS: A total of 798 patients
      were admitted, of whom 443 (55.5%) were female. There were 18 deaths (2.3%).
      Assessment of dehydration status was recorded in 517 (64.8%) of clinical records.
      An alternative or additional diagnosis was made for 214 patients (26.8%).
      Intravenous (IV) fluids were prescribed to 767 patients (96.1%), including 95% of
      141 patients who had documentation of being not severely dehydrated. A history of
      vomiting was documented in 92.1% of all patients. Oral rehydration solution (ORS)
      was given to 629 (78.8%) patients. Doxycycline was given to 380 (47.6%) patients,
      erythromycin to 34 (4.3%), and other antibiotics were used on 247 occasions. Zinc
      was given to 209 (26.2%). DISCUSSION: This retrospective study highlights the
      need for efforts to improve the quality of triage, adherence to clinical
      guidance, and record keeping. CONCLUSIONS: Data collection and analysis of
      clinical practices during an epidemic situation would enable faster
      identification of those areas requiring intervention and improvement.

PMID- 25566809
TI  - Discrepant salivary gland response after radioiodine and MIBG therapies.
AB  - BACKGROUND: A retrospective study using PET/CT imaging with 124I-labeled
      metaiodobenzylguanidine (124I-MIBG) was performed to estimate the (radiation)
      absorbed dose to the salivary glands in neuroendocrine cancer patients undergoing
      131I-MIBG therapy and to compare these results with those in radioiodine (131I
      iodide) therapy. METHODS: Twenty-seven patients received individual 124I-MIBG
      PET/CT dosimetries, among whom 18 had not previously undergone any MIBG therapies
      (patient group before treatment) and 9 had already received MIBG therapies prior
      to the tracer dosimetries (patient group after treatment). For each patient,
      three or four 124I-MIBG PET/CT scans were performed at approximately 4 and 24
      hours, as well as at approximately 48 or/and >=96 hours after tracer injection.
      The absorbed doses per administered 131I-MIBG activity to the submandibular and
      parotid glands were calculated based on the MIRD concept, with its assumption of
      a uniform glandular activity distribution. RESULTS: The mean+/-standard deviation
      of the (self-)absorbed dose per activity averaged over both patient groups and
      salivary gland types was 0.53+/-0.24 Gy/GBq (median, 0.49 Gy/GBq; range, 0.17
      1.38 Gy/GBq). The absorbed doses per activity of the patient group before
      treatment did not significantly deviate from those of the patient group after
      treatment (P=0.67). In the patient group after treatment, the mean+/-standard
      deviation of the cumulative 131I-MIBG activity was 20+/-12 GBq (median, 16 GBq;
      range, 10-50 GBq). Among the patient groups, no significant absorbed dose
      difference was found between the submandibular and parotid glands (P>0.24). In
      comparison to radioiodine therapy, the estimated absorbed dose per activity in
      MIBG was significantly higher (P<0.001), on average twice as high, contradicting
      the relationship between the absorbed dose and clinical observation of glandular
      side effects. CONCLUSIONS: The discrepant salivary gland responses in MIBG and
      radioiodine therapies suggest a different radiotherapeutical distribution on
      microscopic scale within the glandular tissue and prove the clinical relevance of
      a microdosimetric analysis.

PMID- 25566810
TI  - Topological quantum transitions in a two-band Chern insulator with n = 2.
AB  - Based on a two-band Chern insulator with Chern number n = 2, we study the
      transport properties and the topological phase transition induced by either an
      external magnetic field or disorder. In this paper, a characteristic topological
      phase transition from n = 2 to n = 0, which is in sharp contrast to the plateau
      plateau transition in the integer quantum Hall effect, is observed. This unique
      feature of the phase transition should be ascribed to the minimal two-band
      feature of this high Chern insulator. We prove this result by studying the
      transport properties of many different geometrical structures and the evolution
      of the Chern number in the presence of magnetic fields and strong disorder.

PMID- 25566808
TI  - Low-dose decitabine promotes megakaryocyte maturation and platelet production in
      healthy controls and immune thrombocytopenia.
AB  - Impaired megakaryocyte maturation and insufficient platelet production have been
      shown to participate in the pathogenesis of immune thrombocytopenia (ITP). Our
      previous study demonstrated that low expression of tumour necrosis factor-related
      apoptosis-inducing ligand (TRAIL) in megakaryocytes contributed to impaired
      platelet production in ITP. Decitabine (DAC), a demethylating agent, is known to
      promote cell differentiation and maturation at low doses. However, whether
      decitabine is potential in promoting megakaryocyte maturation and platelet
      release in ITP is unclear. In this study, we evaluated the effect of DAC on
      megakaryocyte maturation and platelet release in the presence of ITP plasma that
      has been shown to cause impaired megakaryocyte maturation and platelet
      production. We observed that low-dose DAC (10 nM) could significantly increase
      the number of mature polyploid (>= 4N) megakaryocytes in cultures with plasma
      from healthy controls and more than one-half of ITP patients in vitro.
      Furthermore, the number of platelets released from these megakaryocytes
      significantly increased compared with those untreated with DAC. In these
      megakaryocytes, DAC significantly enhanced TRAIL expression via decreasing its
      promoter methylation status. These findings demonstrate that low-dose DAC can
      promote megakaryocyte maturation and platelet production and enhance TRAIL
      expression in megakaryocytes in healthy controls and ITP. The potential
      therapeutic role of low-dose DAC may be beneficial for thrombocytopenic
      disorders.

PMID- 25566812
TI  - Did the tobacco industry inflate estimates of illicit cigarette consumption in
      Asia? An empirical analysis.
AB  - OBJECTIVE: Estimates of illicit cigarette consumption are limited and the data
      obtained from studies funded by the tobacco industry have a tendency to inflate
      them. This study aimed to validate an industry-funded estimate of 35.9% for Hong
      Kong using a framework taken from an industry-funded report, but with more
      transparent data sources. METHODS: Illicit cigarette consumption was estimated as
      the difference between total cigarette consumption and the sum of legal domestic
      sales and legal personal imports (duty-free consumption). Reliable data from
      government reports and scientifically valid routine sources were used to estimate
      the total cigarette consumption by Hong Kong smokers and legal domestic sales in
      Hong Kong. Consumption by visitors and legal duty-free consumption by Hong Kong
      passengers were estimated under three scenarios for the assumptions to examine
      the uncertainty around the estimate. A two-way sensitivity analysis was conducted
      using different levels of possible undeclared smoking and under-reporting of self
      reported daily consumption. RESULTS: Illicit cigarette consumption was estimated
      to be about 8.2-15.4% of the total cigarette consumption in Hong Kong in 2012
      with a midpoint estimate of 11.9%, as compared with the industry-funded estimate
      of 35.9% of cigarette consumption. The industry-funded estimate was inflated by
      133-337% of the probable true value. Only with significant levels of under
      reporting of daily cigarette consumption and undeclared smoking could we
      approximate the value reported in the industry-funded study. CONCLUSIONS: The
      industry-funded estimate inflates the likely levels of illicit cigarette
      consumption.

PMID- 25566813
TI  - Normativity under change: Older persons with implantable cardioverter
      defibrillator.
AB  - BACKGROUND: In modern society, death has become 'forbidden' fed by the medical
      technology to conquer death. The technological paradigm is challenged by a social
      liberal political ideology in postmodern Western societies. The question raised
      in this study was as follows: Which arguments, attitudes, values and paradoxes
      between modern and postmodern tendencies concerning treatment and care of older
      persons with an implantable cardioverter defibrillator appear in the literature?
      AIMS: The aim of this study was to describe and interpret how the field of
      tension concerning older persons with an implantable cardioverter defibrillator -
      especially end-of-life issues - has been expressed in the literature throughout
      the last decade. METHODS: Paul Ricoeur's reflexive interpretive approach was used
      to extract the meaningful content of the literature involving qualitative,
      quantitative and normative literature. Analysis and interpretation involved naive
      reading, structural analysis and critical interpretation. ETHICAL CONSIDERATIONS:
      The investigation complied with the principles outlined in the Declaration of
      Helsinki. FINDINGS AND DISCUSSIONS: The unifying theme was 'Normativity under
      change'. The sub-themes were 'Death has become legitimate', 'The technological
      imperative is challenged' and 'Patients and healthcare professionals need to talk
      about end-of-life issues'. There seems to be a considerable distance between the
      normative approach of how practice ought to be and findings in empirical studies.
      CONCLUSION: Modern as well as postmodern attitudes and perceptions illustrate
      contradictory tendencies regarding deactivation of the implantable cardioverter
      defibrillator and replacement of the implantable cardioverter defibrillator in
      older persons nearing the end of life. The tendencies challenge each other in a
      struggle to gain position. On the other hand, they can also complement each other
      because professionalism and health professional expertise cannot stand alone when
      the patient's life is at stake but must be unfolded in an alliance with the
      patient who needs to be understood and accepted in his vulnerability.

PMID- 25566811
TI  - Smoke-free multiunit housing: a review of the scientific literature.
AB  - OBJECTIVE: Multiunit housing (MUH) residents are susceptible to secondhand smoke
      (SHS) exposure, which can transfer between living units. This review summarises
      existing scientific literature relevant to smoke-free MUH, discusses knowledge
      gaps and provides recommendations for future research to inform public health
      action. DATA SOURCES: We conducted a systematic search of peer-reviewed articles
      using three databases: EBSCOhost CINAHL, PubMed and Web of Science. STUDY
      SELECTION: Article titles, abstracts and text were reviewed to ascertain three
      inclusion criteria: (1) English language; (2) conducted in the USA; (3) reported
      on baseline data, development, implementation or evaluation of smoke-free MUH.
      DATA EXTRACTION: We used a multistep process to identify eligible articles: (1)
      two reviewers separately evaluated article titles; (2) two reviewers separately
      evaluated abstracts and (3) one reviewer read each article and determined
      inclusion eligibility. DATA SYNTHESIS: We identified and included 35 articles
      published during 2001-2014, grouped based on broad themes: MUH resident (n=16);
      MUH operator (n=6); environmental monitoring and biomarkers (n=9); economic
      (n=2); legal (n=3); and implementation process and policy impact (n=8). Studies
      with multiple themes were included in all relevant groups. CONCLUSIONS: Existing
      literature has focused on self-reported, cross-sectional studies of MUH residents
      and operators; some studies of environmental markers, biomarkers and economic
      indicators have also been conducted. Future research on smoke-free MUH policy
      compliance and enforcement, and on the impact of these policies on smoking
      behaviours and health outcomes, could further inform public health planning,
      policy and practice. Despite these gaps, the current literature provides
      sufficient evidence for action to eliminate SHS exposure in MUH.

PMID- 25566814
TI  - A study of nurses' ethical climate perceptions: Compromising in an uncompromising
      environment.
AB  - BACKGROUND: Acting ethically, in accordance with professional and personal moral
      values, lies at the heart of nursing practice. However, contextual factors, or
      obstacles within the work environment, can constrain nurses in their ethical
      practice - hence the importance of the workplace ethical climate. Interest in
      nurse workplace ethical climates has snowballed in recent years because the
      ethical climate has emerged as a key variable in the experience of nurse moral
      distress. Significantly, this study appears to be the first of its kind carried
      out in New Zealand. AIM/OBJECTIVE: The purpose of this study was to explore and
      describe how registered nurses working on a medical ward in a New Zealand
      hospital perceive their workplace ethical climate. RESEARCH
      DESIGN/PARTICIPANTS/CONTEXT: This was a small, qualitative descriptive study.
      Seven registered nurses were interviewed in two focus group meetings. An
      inductive method of thematic data analysis was used for this research. ETHICAL
      CONSIDERATIONS: Ethics approval for this study was granted by the New Zealand
      Ministry of Health's Central Regional Health and Disability Ethics Committee on
      14 June 2012. FINDINGS: The themes identified in the data centred on three
      dominant elements that - together - shaped the prevailing ethical climate:
      staffing levels, patient throughput and the attitude of some managers towards
      nursing staff. DISCUSSION: While findings from this study regarding staffing
      levels and the power dynamics between nurses and managers support those from
      other ethical climate studies, of note is the impact of patient throughput on
      local nurses' ethical practice. This issue has not been singled out as having a
      detrimental influence on ethical climates elsewhere. CONCLUSION: Moral distress
      is inevitable in an ethical climate where the organisation's main priorities are
      perceived by nursing staff to be budget and patient throughput, rather than
      patient safety and care.

PMID- 25566815
TI  - Coercion in nursing homes: Perspectives of patients and relatives.
AB  - BACKGROUND: Studies have demonstrated the extensive use of coercion in Norwegian
      nursing homes, which represents ethical, professional as well as legal challenges
      to the staff. We have, however, limited knowledge of the experiences and views of
      nursing home patients and their relatives. OBJECTIVES: The aim of this study is
      to explore the perspectives of nursing home patients and next of kin on the use
      of coercion; are there situations where the use of coercion can be defended, and
      if so, under which circumstances? METHODS: The data are based on individual
      interviews with 35 patients living in six nursing homes and seven focus group
      interviews with 60 relatives. ETHICAL CONSIDERATIONS: Participation was based on
      written informed consent, and the study was approved by the Regional Committees
      for Medical and Health Research Ethics. RESULTS: More than half of the patients
      and the majority of the relatives accepted the use of coercion, trusting the
      staff to act in the patient's best interest. However, the acceptance of coercion
      is strongly related to the patients' lack of understanding, to prevent health
      risks and to preserve the patient's dignity. CONCLUSION: The majority of nursing
      home patients and relatives accepted the use of coercion in specific situations,
      while at the same time they emphasised the need to try alternative strategies
      first. There is still a need for good qualitative research on the use of coercion
      in nursing homes, especially with a closer focus on the perspectives and
      experiences of nursing home patients.

PMID- 25566816
TI  - Preliminary assessment of the potential role of urbanization in the distribution
      of carbamate and organophosphate resistant populations of Culex species in Ghana.
AB  - BACKGROUND: Besides its role as a pathogen vector, Culex species also indirectly
      promotes the transmission of malaria if the use of bed nets or indoor residual
      spraying is discontinued due to a lack of insecticide efficacy against it. A
      recent survey revealed widespread occurrence of pyrethroid resistance among urban
      populations of this mosquito in Ghana. In order to plan and implement insecticide
      based resistance management strategies, this study was carried out to assess
      resistance status of Culex species to organophosphate and carbamate in urban
      areas in Ghana and the possible mechanisms involved as well as environmental
      factors associated with its distribution. METHODS: Mosquito larvae were sampled
      from various land use and ecological settings and in different seasons. In
      adults, susceptibility to organophosphates (fenitrothion, malathion) and
      carbamates (propoxur, bendiocarb) were determined. Mixed function oxidase (MFO)
      and alpha- and beta-esterase assays, as well as a PCR diagnostic assay to
      determine ace1 mutation were performed in individual mosquitoes. RESULTS: Culex
      quinquefasciatus as well as C. decens and other unidentified Culex species were
      found breeding in polluted water bodies in the study sites. Across all sites and
      seasons, carbamate induced mortality was 94.1% +/- 15.4 whereas mortality caused
      by organophosphate was 99.5% +/- 2.2. In addition, ace1 mutation and high levels
      of esterases were detected in some of the mosquito populations. There was a
      strong correlation between susceptibility status of the mosquitoes and the level
      of absorbance of beta-esterase (Pearson r=- 0.841, p=0.004). CONCLUSIONS: The
      study found low prevalence of resistance to carbamate and organophosphate
      insecticides among Culex species from Ghana. However, there were populations with
      ace1 mutations and high levels of esterases, which can confer high resistance to
      these classes of insecticides. Thus, it is important to monitor activities or
      behaviour that has the potential to select for carbamate and organophosphate
      resistance populations.

PMID- 25566817
TI  - Rationale and Design of the Double-Blind, Randomized, Placebo-Controlled
      Multicenter Trial on Efficacy of Early Initiation of Eplerenone Treatment in
      Patients with Acute Heart Failure (EARLIER).
AB  - BACKGROUND AND AIMS: Aldosterone is one of the major factors to cause organ
      damage during an acute phase of heart failure (HF), and many reports have
      demonstrated that patients with acute decompensated HF (ADHF) have high blood
      aldosterone concentrations, and the high aldosterone concentrations predict poor
      prognosis in patients with HF. These findings suggest that eplerenone, an
      antagonist of aldosterone receptors may provide a new concept and strategy for
      the treatment of ADHF, protecting the heart and other organs during chronic
      phases, depending on the restoration of hemodynamic abnormalities. METHODS:
      EARLIER is an event-driven clinical trial with an estimated enrolment of 300
      patients hospitalized with ADHF with reduced left ventricular ejection fraction.
      ADHF includes ischemic or non-ischemic HF, and patients can be enrolled within 72
      h after the visit to the hospital. We randomize the patients taking standard
      therapies for ADHF to the eplerenone and placebo groups. Eplerenone, either 25 or
      50 mg, is administered for 6 months in the eplerenone group, and the
      corresponding placebo is administered in the placebo group on top of the standard
      care. We set the primary endpoint as the incidence of the composite endpoint
      (cardiac death or first re-hospitalization due to cardiac disease) 6 months after
      the enrollment, and also check the quality of life, i.e., exercise capacity and
      safety features of eplerenone. CONCLUSION AND PERSPECTIVES: EARLIER is a clinical
      trial of eplerenone targeting ADHF and also the first multicenter investigator
      initiated phase III trial in the cardiovascular field in Japan, funded by the
      Japanese government.

PMID- 25566819
TI  - Special section on LGBT resilience across cultures: introduction.
AB  - This special section addresses a gap area of resilience and LGBT well-being.
      Although comprehensive global diversity regarding LGBT resilience was challenging
      to find, the special section includes representation from outside the US (Israel
      and Hong Kong), ethnic/racially diverse domestic populations, immigration, and
      one population for which LGBT identities might be considered marginalized
      Christians in the US. The full range of LGBT identities are represented in the
      issue along with persons identifying as queer or questioning, although
      transgendered people were less well represented than lesbian, gay or bisexual
      identities. 

PMID- 25566818
TI  - Identification of predominant yeasts associated with artisan Mexican cocoa
      fermentations using culture-dependent and culture-independent approaches.
AB  - The process of cocoa fermentation is a very important step for the generation or
      aromatic compounds, which are attributable to the metabolism of the
      microorganisms involved. There are some reports about this process and the
      identification of microorganisms; however, there are no reports identifying the
      yeasts involved in a Mexican cocoa fermentation process using molecular biology
      techniques, including restricted fragment length polymorphism (RFLP) and
      denaturing gradient gel electrophoresis (DGGE). The aim of this study was to
      identify the main yeast species associated with Mexican cocoa fermentations
      employing culture-dependent and -independent techniques achieving two samplings
      with a 1 year time difference at the same site. Isolation of the microorganisms
      was performed in situ. Molecular identification of yeast isolates was achieved by
      RFLP analysis and rDNA sequencing. Total DNA from the microorganisms on the cocoa
      beans was utilized for the DGGE analysis. Bands from the DGGE gels were excised
      and sequenced. Nineteen isolated yeasts were identified (al specie level), three
      of which had never before been associated with cocoa fermentations worldwide. The
      detected predominant yeast varied from one technique to another. Hanseniaspora
      sp. resulted dominant in DGGE however Saccharomyces cerevisiae was the principal
      isolated species. In conclusion, the culture-dependent and -independent
      techniques complement each other showing differences in the main yeasts involved
      in spontaneous cocoa fermentation, probably due to the physiological states of
      the viable but non culturable yeasts. Furthermore important differences between
      the species detected in the two samplings were detected.

PMID- 25566820
TI  - A novel frameshift mutation in FGF14 causes an autosomal dominant episodic
      ataxia.
AB  - Episodic ataxias (EAs) are a heterogeneous group of neurological disorders
      characterized by recurrent attacks of ataxia. Mutations in KCNA1 and CACNA1A
      account for the majority of EA cases worldwide. We recruited a two-generation
      family affected with EA of unknown subtype and performed whole-exome sequencing
      on two affected members. This revealed a novel heterozygous mutation
      c.211_212insA (p.I71NfsX27) leading to a premature stop codon in FGF14. Mutations
      in FGF14 are known to cause spinocerebellar ataxia type 27 (SCA27). Sanger
      sequencing confirmed segregation within the family. Our findings expand the
      phenotypic spectrum of SCA27 by underlining the possible episodic nature of this
      ataxia. 

PMID- 25566821
TI  - Langerhans cell histiocytosis causing acute optic neuropathy.
AB  - PURPOSE: Langerhans cell histiocytosis (LCH) arising from the skull base is a
      rare acute optic neuropathy cause. We describe a clinical approach for the
      purpose of optic nerve decompression and simultaneous lesion excision. This is
      the first case of visual improvement following decompression operation via
      endoscopic endonasal approach for acute optic neuropathy that is produced by LCH.
      METHODS: An 11-year-old boy presented with a 2-week history of visual
      deterioration. Radiological evidence of compressive optic neuropathy by an
      expansile soft tissue mass around the optic canal was observed. The patient
      underwent an endoscopic endonasal optic nerve decompression and subtotal tumor
      removal. RESULTS: His visual impairment improved dramatically after the
      operation. CONCLUSIONS: Acute optic neuropathy can be elicited by LCH arising in
      the sphenoid-ethmoid bone. Early decompression is the key to vision salvage. An
      endoscopic endonasal approach may be a good therapeutic option in this situation.

PMID- 25566822
TI  - Varying clinical and imaging outcomes in patients with spontaneous thrombosis of
      vein of Galen malformation--a report of two cases.
AB  - BACKGROUND: Vein of Galen malformations are rare congenital intracranial vascular
      malformations. The pathophysiological consequences usually manifest as high
      output cardiac failure and neurological symptoms secondary to cerebral venous
      congestion and abnormal CSF flow. Management of these patients is complex.
      Indications and time to intervene are decided depending upon the age of child,
      clinical presentation, and multisystemic neonatal scores. Many of these children
      presenting early and who are not in cardiac failure are expectantly followed up.
      Spontaneous thrombosis of the vein of Galen malformation is a rare occurrence in
      these as such rare vascular malformations. METHODS: This review reports two cases
      of spontaneous thrombosis of the vein of Galen malformations with varying
      clinical as well as imaging outcomes. Possible pathophysiologic mechanisms are
      discussed with review of literature. RESULTS: This report highlights the
      importance of vigilant clinical and imaging follow-up even after spontaneous
      thrombosis in the vein of Galen malformations.

PMID- 25566823
TI  - Erratum to: Cutting efficiency of nickel-titanium rotary and reciprocating
      instruments after prolonged use.

PMID- 25566824
TI  - Mixture of ischemia and hibernation in a patient with severe diagonal disease:
      Value of perfusion and metabolic PET imaging.

PMID- 25566825
TI  - Risk of anaphylaxis with repeated courses of rasburicase: a Research on Adverse
      Drug Events and Reports (RADAR) project.
AB  - BACKGROUND: Rasburicase, a recombinant urate oxidase, is used to rapidly
      metabolize uric acid in patients with hyperuricaemia. Rasburicase is an
      immunogenic therapeutic protein, which has been shown to elicit antibody response
      in 64 % of healthy volunteers within 1-6 weeks after the initial course, with
      persistent antibodies for over 1 year. Drug labelling indicates that anaphylaxis
      rarely occurs (in <1 % of patients) after a single course of therapy with
      rasburicase, but there are no data available on the incidence of anaphylaxis in
      patients receiving a subsequent rasburicase course. OBJECTIVE: The objective of
      this study was to determine the incidence of anaphylaxis after multiple treatment
      courses of rasburicase. METHODS: A retrospective chart review was performed on 97
      consecutively treated patients who received repeated courses of rasburicase for
      hyperuricaemia. RESULTS: None of the 97 patients who were reviewed experienced
      anaphylaxis during the first rasburicase course; however, six patients (6.2 %)
      experienced anaphylaxis during a subsequent rasburicase treatment course (p =
      0.03). CONCLUSION: Anaphylaxis after a second course of rasburicase appears to
      occur more frequently than described in the US Food and Drug Administration
      approved package insert for initial treatment courses. Given the serious nature
      of anaphylactic events, caution is advised when administering repeated courses of
      rasburicase.

PMID- 25566826
TI  - Optimal Cerebral Perfusion Pressure Management at Bedside: A Single-Center Pilot
      Study.
AB  - BACKGROUND: Guidelines recommend cerebral perfusion pressure (CPP) values of 50
      70 mmHg and intracranial pressure lower than 20 mmHg for the management of acute
      traumatic brain injury (TBI). However, adequate individual targets are still
      poorly addressed, since patients have different perfusion thresholds. Bedside
      assessment of cerebral autoregulation may help to optimize individual CPP-guided
      treatment. OBJECTIVE: To assess staff compliance and outcome impact of a new
      method of autoregulation-guided treatment (CPPopt) based on continuous evaluation
      of cerebrovascular reactivity (PRx). METHODS: Prospective pilot study of severe
      TBI adult patients managed with continuous multimodal brain monitoring in a
      single Neurocritical Care Unit (NCCU). Every minute CPPopt was automatically
      estimated, based on the previous 4-h window, as the CPP with the lowest PRx
      indicating the best cerebrovascular pressure reactivity. Patients were managed
      with CPPopt targets whenever possible and otherwise CPP was managed following
      general/international guidelines. In addition, other offline CPPopt estimates
      were calculated using cerebral oximetry (COx-CPPopt), brain tissue oxygenation
      (ORxs-CPPopt), and cerebral blood flow (CBFx-CPPopt). RESULTS: Eighteen patients
      with a total multimodal brain monitoring time of 5,520 h were enrolled. During
      the total monitoring period, 11 patients (61 %) had a CPPopt U-shaped curve, 5
      patients (28 %) had either ascending or descending curves, and only 2 patients
      (11 %) had no fitted curve. Real CPP correlated significantly with calculated
      CPPopt (r = 0.83, p < 0.0001). Preserved autoregulation was associated with
      greater Glasgow coma score on admission (p = 0.01) and better outcome (p = 0.01).
      We demonstrated that patients with the larger discrepancy (>10 mm Hg) between
      real CPP and CPPopt more likely have had adverse outcome (p = 0.04). Comparison
      between CPPopt and the other estimates revealed similar limits of precision. The
      lowest bias (-0.1 mmHg) was obtained with COx-CPPopt (NIRS). CONCLUSION: Targeted
      individual CPP management at the bedside using cerebrovascular pressure
      reactivity seems feasible. Large deviation from CPPopt seems to be associated
      with adverse outcome. The COx-CPPopt methodology using non-invasive CO (NIRS)
      warrants further evaluation.

PMID- 25566827
TI  - A hand hygiene intervention to reduce infections in child daycare: a randomized
      controlled trial.
AB  - Infections are common in children attending daycare centres (DCCs). We evaluated
      the effect of a hand hygiene (HH) intervention for caregivers on the incidence of
      gastrointestinal and respiratory infections in children. The intervention was
      evaluated in a two-arm cluster randomized controlled trial. Thirty-six DCCs
      received the intervention including HH products, training sessions, and
      posters/stickers. Thirty-five control DCCs continued usual practice. Incidence of
      episodes of diarrhoea and the common cold in children was monitored by parents
      during 6 months. Using multilevel Poisson regression, incidence rate ratios
      (IRRs) with 95% confidence intervals (CIs) were obtained. Diarrhoeal incidence
      was monitored in 545 children for 91 937 days. During follow-up, the incidence
      was 3.0 episodes per child-year in intervention DCCs vs. 3.4 in control DCCs (IRR
      0.90, 95% CI 0.73-1.11). Incidence of the common cold was monitored in 541
      children for 91 373 days. During follow-up, the incidence was 8.2 episodes per
      child-year in intervention DCCs vs. 7.4 in control DCCs (IRR 1.07, 95% CI 0.97
      1.19). In this study, no evidence for an effect of the intervention was
      demonstrated on the incidence of episodes of diarrhoea and the common cold. 

PMID- 25566828
TI  - Inhibition of TGFbeta type I receptor activity facilitates liver regeneration
      upon acute CCl4 intoxication in mice.
AB  - Liver exhibits a remarkable maintenance of functional homeostasis in the presence
      of a variety of damaging toxic factors. Tissue regeneration involves cell
      replenishment and extracellular matrix remodeling. Key regulator of homeostasis
      is the transforming growth factor-beta (TGFbeta) cytokine. To understand the role
      of TGFbeta during liver regeneration, we used the single-dose carbon
      tetrachloride (CCl4) treatment in mice as a model of acute liver damage. We
      combined this with in vivo inhibition of the TGFbeta pathway by a small molecule
      inhibitor, LY364947, which targets the TGFbeta type I receptor kinase [activin
      receptor-like kinase 5 (ALK5)] in hepatocytes but not in activated stellate
      cells. Co-administration of LY364947 inhibitor and CCl4 toxic agent resulted in
      enhanced liver regeneration; cell proliferation (measured by PCNA, phosphorylated
      histone 3, p21) levels were increased in CCl4 + LY364947 versus CCl4-treated
      mice. Recovery of CCl4-metabolizing enzyme CYP2E1 expression in hepatocytes is
      enhanced 7 days after CCl4 intoxication in the mice that received also the
      TGFbeta inhibitor. In summary, a small molecule inhibitor that blocks ALK5
      downstream signaling and halts the cytostatic role of TGFbeta pathway results in
      increased cell regeneration and improved liver function during acute liver
      damage. Thus, in vivo ALK5 modulation offers insight into the role of TGFbeta,
      not only in matrix remodeling and fibrosis, but also in cell regeneration. 

PMID- 25566829
TI  - Molecular responses to ischemia and reperfusion in the liver.
AB  - Ischemia/reperfusion (IR) injury occurs when oxygen is rapidly reintroduced into
      ischemic tissue, resulting in cell death and necrotic tissue damage. This is a
      major concern during liver transplantation procedures since there is an
      inevitable interruption and subsequent restoration of circulation. IR injury in
      liver tissue is initiated through reactive oxygen species (ROS), which are
      generated by hepatocytes during IR insult. Although these ROS are thought to play
      a protective roll since they are known to activate several pathways involved in
      the hypoxic response, they also trigger a localized sterile immune response that
      results in the recruitment of Kupffer cells and neutrophils to the site of IR
      insult. These immune cells generate larger quantities of ROS that trigger
      apoptosis and oncotic necrosis in liver tissue. In this review, we will summarize
      what is currently known about the response of liver tissue to IR insult at the
      molecular level.

PMID- 25566831
TI  - Identification and prioritization of management practices to reduce methylmercury
      exports from wetlands and irrigated agricultural lands.
AB  - The Sacramento-San Joaquin Delta's (Delta) beneficial uses for humans and
      wildlife are impaired by elevated methylmercury (MeHg) concentrations in fish.
      MeHg is a neurotoxin that bioaccumulates in aquatic food webs. The total maximum
      daily load (TMDL) implementation plan aimed at reducing MeHg in Delta fish
      obligates dischargers to conduct MeHg control studies. Over 150 stakeholders
      collaborated to identify 24 management practices (MPs) addressing MeHg nonpoint
      sources (NPS) in three categories: biogeochemistry (6), hydrology (14), and
      soil/vegetation (4). Land uses were divided into six categories: permanently and
      seasonally flooded wetlands, flooded and irrigated agricultural lands,
      floodplains, and brackish-fresh tidal marshes. Stakeholders scored MPs based on
      seven criteria: scientific certainty, costs, MeHg reduction potential, spatial
      applicability, technical capacity to implement, negative impacts to beneficial
      uses, and conflicting requirements. Semi-quantitative scoring for MPs applicable
      to each land use (totaling >400 individual scores) led to consensus-based
      prioritization. This process relied on practical experience from diverse and
      accomplished NPS stakeholders and synthesis of 17 previous studies. Results
      provide a comprehensive, stakeholder-driven prioritization of MPs for wetland and
      irrigated agricultural land managers. Final prioritization highlights the most
      promising MPs for practical application and control study, and a secondary set of
      MPs warranting further evaluation. MPs that address hydrology and soil/vegetation
      were prioritized because experiences were positive and implementation appeared
      more feasible. MeHg control studies will need to address the TMDL conundrum that
      MPs effective at reducing MeHg exports could both exacerbate MeHg exposure and
      contend with other management objectives on site. 

PMID- 25566832
TI  - Predicted changes in interannual water-level fluctuations due to climate change
      and its implications for the vegetation of the Florida Everglades.
AB  - The number of dominant vegetation types (wet prairies, sawgrass flats, ridges and
      sloughs, sloughs, and tree islands) historically and currently found in the
      Everglades, FL, USA, as with other wetlands with standing water, appears to be
      primarily a function of the magnitude of interannual water-level fluctuations.
      Analyses of 40 years of water-depth data were used to estimate the magnitude of
      contemporary (baseline) water-level fluctuations in undisturbed ridge and slough
      landscapes. Baseline interannual water-level fluctuations above the soil surface
      were at least 1.5 m. Predicted changes in interannual water-level fluctuations in
      2060 were examined for seven climate change scenarios. When rainfall is predicted
      to increase by 10 %, the wettest scenario, the interannual range of water-level
      fluctuation increases to 1.8 m above the soil surface in sloughs. When rainfall
      is predicted to decrease by 10 % and temperatures to increase by 1.5  degrees C,
      the driest scenario, the range of interannual range of water-level fluctuations
      is predicted to decrease to 1.2 m above the soil surface in sloughs. A change of
      25-30 cm in interannual water-level fluctuations is needed to change the number
      of vegetation types in a wetland. This suggests that the two most extreme climate
      change scenarios could have a significant impact on the overall structure of
      wetland vegetation, i.e., the number of vegetation types or zones, found in the
      Everglades.

PMID- 25566830
TI  - The role of Smad7 in oral mucositis.
AB  - Oral mucositis, a severe oral ulceration, is a common toxic effect of radio- or
      chemoradio-therapy and a limiting factor to using the maximum dose of radiation
      for effective cancer treatment. Among cancer patients, at least 40% and up to
      70%, of individuals treated with standard chemotherapy regimens or upper-body
      radiation, develop oral mucositis. To date, there is no FDA approved drug to
      treat oral mucositis in cancer patients. The key challenges for oral mucositis
      treatment are to repair and protect ulcerated oral mucosa without promoting
      cancer cell growth. Oral mucositis is the result of complex, multifaceted
      pathobiology, involving a series of signaling pathways and a chain of
      interactions between the epithelium and submucosa. Among those pathways and
      interactions, the activation of nuclear factor-kappa B (NF-kappaB) is critical to
      the inflammation process of oral mucositis. We recently found that activation of
      TGFbeta (transforming growth factor beta) signaling is associated with the
      development of oral mucositis. Smad7, the negative regulator of TGFbeta
      signaling, inhibits both NF-kappaB and TGFbeta activation and thus plays a
      pivotal role in the prevention and treatment of oral mucositis by attenuating
      growth inhibition, apoptosis, and inflammation while promoting epithelial
      migration. The major objective of this review is to evaluate the known functions
      of Smad7, with a particular focus on its molecular mechanisms and its function in
      blocking multiple pathological processes in oral mucositis. 

PMID- 25566833
TI  - Relative linkages of canopy-level CO2 fluxes with the climatic and environmental
      variables for US deciduous forests.
AB  - We used a simple, systematic data-analytics approach to determine the relative
      linkages of different climate and environmental variables with the canopy-level,
      half-hourly CO2 fluxes of US deciduous forests. Multivariate pattern recognition
      techniques of principal component and factor analyses were utilized to classify
      and group climatic, environmental, and ecological variables based on their
      similarity as drivers, examining their interrelation patterns at different sites.
      Explanatory partial least squares regression models were developed to estimate
      the relative linkages of CO2 fluxes with the climatic and environmental
      variables. Three biophysical process components adequately described the system
      data variances. The 'radiation-energy' component had the strongest linkage with
      CO2 fluxes, whereas the 'aerodynamic' and 'temperature-hydrology' components were
      low to moderately linked with the carbon fluxes. On average, the 'radiation
      energy' component showed 5 and 8 times stronger carbon flux linkages than that of
      the 'temperature-hydrology' and 'aerodynamic' components, respectively. The
      similarity of observed patterns among different study sites (representing
      gradients in climate, canopy heights and soil-formations) indicates that the
      findings are potentially transferable to other deciduous forests. The
      similarities also highlight the scope of developing parsimonious data-driven
      models to predict the potential sequestration of ecosystem carbon under a
      changing climate and environment. The presented data-analytics provides an
      objective, empirical foundation to obtain crucial mechanistic insights;
      complementing process-based model building with a warranted complexity. Model
      efficiency and accuracy (R(2) = 0.55-0.81; ratio of root-mean-square error to the
      observed standard deviations, RSR = 0.44-0.67) reiterate the usefulness of
      multivariate analytics models for gap-filling of instantaneous flux data.

PMID- 25566834
TI  - Habitat loss and modification due to gas development in the Fayetteville shale.
AB  - Hydraulic fracturing and horizontal drilling have become major methods to extract
      new oil and gas deposits, many of which exist in shale formations in the
      temperate deciduous biome of the eastern United States. While these technologies
      have increased natural gas production to new highs, they can have substantial
      environmental effects. We measured the changes in land use within the maturing
      Fayetteville Shale gas development region in Arkansas between 2001/2002 and 2012.
      Our goal was to estimate the land use impact of these new technologies in natural
      gas drilling and predict future consequences for habitat loss and fragmentation.
      Loss of natural forest in the gas field was significantly higher compared to
      areas outside the gas field. The creation of edge habitat, roads, and developed
      areas was also greater in the gas field. The Fayetteville Shale gas field fully
      developed about 2% of the natural habitat within the region and increased edge
      habitat by 1,067 linear km. Our data indicate that without shale gas activities,
      forest cover would have increased slightly and edge habitat would have decreased
      slightly, similar to patterns seen recently in many areas of the southern U.S. On
      average, individual gas wells fully developed about 2.5 ha of land and modified
      an additional 0.5 ha of natural forest. Considering the large number of wells
      drilled in other parts of the eastern U.S. and projections for new wells in the
      future, shale gas development will likely have substantial negative effects on
      forested habitats and the organisms that depend upon them.

PMID- 25566837
TI  - [Benefit assessment of medical services in German health service - legal
      framework, historical and international perspective].
AB  - The term benefit describes the (positive) causal, patient-relevant consequences
      of medical interventions, whether diagnostic or therapeutic. Benefit assessments
      form the basis of rational decision-making within a health care system. They are
      based on clinical trials that are able to provide valid answers to the question
      regarding the relevant benefit or harm that can be caused by an intervention. In
      Germany, evidence-based benefit assessments are fixed by law, i.e., the Social
      Code Book V. The application and the practical impact of these assessments could
      be improved. 

PMID- 25566836
TI  - [Interaction between humans and intestinal bacteria as a determinant for
      intestinal health : intestinal microbiome and inflammatory bowel diseases].
AB  - Recent scientific results underline the importance of the intestinal microbiome,
      the totality of all intestinal microbes and their genes, for the health of the
      host organism. The intestinal microbiome can therefore be considered as a kind of
      "external organ". It has been shown that the intestinal microbiota is a complex
      and dynamic ecosystem that influences host immunity and metabolism beyond the
      intestine. The composition and functionality of the intestinal microbiota is of
      major importance for the development and maintenance of intestinal functions.
      Inflammatory bowel diseases (IBD) are characterized by dysregulated interactions
      between the host and its microbiota.The present contribution summarizes current
      knowledge of the composition and development of the intestinal microbiome and
      gives an overview of the bidirectional interaction between host and microbiota.
      The contribution informs about insights regarding the role of the intestinal
      microbiota in IBD and finally discusses the protective potential of microbial
      therapies in the context of IBD. 

PMID- 25566835
TI  - Dietary supplementation with sodium nitrite can exert neuroprotective effects on
      global cerebral ischemia/reperfusion in mice.
AB  - BACKGROUND: Nitrite-derived NO protects against middle cerebral artery occlusion
      in mice. We developed a new mouse model of global cerebral ischemia and
      reperfusion (GCI/R) involving reversible occlusion of the major vessels from the
      aortic arch supplying the brain, and investigated neuroprotection with dietary
      sodium nitrite supplementation against GCI/R injury. METHODS: Mice received
      drinking water with (nitrite group) or without (control group) sodium nitrite (2
      mM) for 5 days and underwent 3-min GCI/R by reversible occlusion of major vessels
      from the aortic arch (i.e., brachiocephalic, left common carotid, and left
      subclavian artery). Survival rates and neurological function scores were
      evaluated for up to 5 days after GCI/R. Histopathological studies were performed
      to detect neurological degeneration and caspase-3 activation in serial
      hippocampal sections. RESULTS: In the control group, 17/30 mice (57 %) survived 5
      days after 3-min GCI/R, whereas in the nitrite group 25/30 mice (83 %) survived
      (p < 0.05). The neurological score at 5 days after GCI in control group was
      significantly higher than in the nitrite group. Cerebral blood flow (CBF) during
      GCI was significantly higher in the nitrite group than in the control group,
      while MABP did not differ significantly between groups. Degenerative changes and
      caspase-3 activation in hippocampal sections after GCI were observed in the
      control group but not in the nitrite group. Pretreatment with the NO scavenger c
      PTIO abolished the neuroprotective effects of sodium nitrite. CONCLUSIONS: Sodium
      nitrite supplementation attenuated mortality and neurological impairment after 3
      min GCI in mice; an effect likely mediated via vascular mechanisms involving NO.

PMID- 25566838
TI  - [Biostatistical support for decision making in drug licensing and reimbursement
      exemplified by implications of heterogeneous findings in subgroups of the study
      population].
AB  - In the context of both drug licensing and reimbursement, the target population is
      sometimes restricted to a specific subgroup. In the setting of drug licensing the
      discussion concerns a negative benefit/risk assessment in a relevant subgroup.
      For reimbursement the debate involves the detection of an additional benefit
      compared with standard treatment, which can in some situations not be accepted
      for the overall study population. In their Methods Paper, the Institute for
      Quality and Efficiency in Health Care (IQWiG) refers to published articles that
      name criteria for the evaluation of credibility to claim a therapeutic effect on
      the basis of results in the subgroups of a study population (BMJ 340:850-854,
      2010). A number of these criteria have found their way into the regulatory
      debate, which was recently published in a draft guideline of the European
      Medicines Agency (EMA). However, the significance of the
      interaction/heterogeneity test has been mentioned as one criterion for the
      credibility of a finding in a subgroup of the study population. This aspect is
      critically challenged in our paper. In our estimation, the application of this
      criterion hinders the critical discussion of whether a global treatment effect is
      applicable to relevant subgroups of a study population and the potential
      implications of this. We feel that biostatistical support for decision-making
      strategies should be the same in both worlds, even though in some instances the
      outcomes in a specific situation may be different, depending on the objective to
      be demonstrated. 

PMID- 25566839
TI  - [Benefit assessment in health services research and epidemiology].
AB  - The legal terms "benefit" and "added benefit" and the procedures related to their
      assessment, given the application of a new medical intervention for approval,
      should help to restrict the market to those products for which there is much
      evidence of their benefit or added benefit. The term implies the fiction of an
      overall benefit for all patients with the same disease. However, from the
      perspective of health services research and that of epidemiology the term
      inevitably has to be extended to cover the benefit to a variety of groups of
      patients or users of a broad spectrum of medical interventions in the real world,
      ranging from inpatient treatment to vaccination or screening programs. Thus, the
      assessment of benefit requires a comparison of the new product with all the
      alternatives currently available for routine care, explicitly taking into account
      user preferences. Hence, the assessment of benefit in health services research is
      not one-dimensional and requires new types of studies that go beyond the
      traditional phase III trials (efficacy trials). New approaches are mainly
      developed by comparative effectiveness research (CER). CER studies also use
      randomized designs, because they are currently the best available method for
      causal inferences. However, randomization in CER is extended to a much broader
      framework, including health-related databases, registers, epidemiological
      studies, feasibility studies, and post hoc analyses. CER has developed the
      necessary and appropriate designs and statistical methods. In addition, some of
      these methods allow an adaptive assessment of benefit, which can be used to
      monitor the implementation of new health care interventions or programs. 

PMID- 25566840
TI  - [Interplay between marketing authorization and early benefit assessment of
      drugs].
AB  - The early benefit assessment of newly approved drugs with new active substances
      or new applications that came into force on 1 January 2011 still presents a
      challenge to the parties involved. This article highlights the interplay between
      drug marketing approval and early benefit assessment. The constellation of a
      European, and even an international, largely harmonized, drug authorization
      process, with a mostly nationally regulated drug reimbursement situation causes
      inevitably friction, which could be reduced through joint advice discussions
      during the planning phase for pivotal studies. In 2013, the Federal Institute for
      Drugs and Medical Devices (BfArM) and the Paul Ehrlich Institute (PEI) provided
      439 scientific advice procedures, compared with 98 advice meetings held at the
      Federal Joint Committee (G-BA), for 12 of which the BfArM or PEI provided written
      advice. The numbers of advice meetings held at the G-BA are increasing; however,
      the national competent authorities are involved in only a fraction of these. From
      the perspective of the national competent authorities, prompt and consistent
      involvement in the advice procedures regarding early benefit assessment would be
      useful and desirable. 

PMID- 25566841
TI  - [From the licensure of vaccines to the recommendation of the Standing Committee
      on Vaccination in Germany : criteria for the assessment of benefits and risks].
AB  - Vaccines are among the most effective preventive measures in modern medicine and
      have led to a dramatic decline and-for a few diseases-even to the elimination of
      severely infectious diseases. There are some particularities of the risk-benefit
      assessment of vaccines compared with that of therapeutic drugs. These include the
      fact that vaccines are applied to healthy individuals with the aim of preventing
      an infectious disease, while therapeutic drugs are administered to sick people to
      cure them of an already acquired disease. The acceptable level of risk associated
      with the application of a vaccine is therefore much lower. In addition, high
      vaccination coverage can lead to population-level effects (e.g., the indirect
      protection of unvaccinated individuals) that can confer additional benefits to
      the population overall. When a marketing authorization application (MAA) for a
      novel vaccine is evaluated, conclusions are made regarding its quality, safety,
      and efficacy, and a benefit-risk assessment is carried out accordingly. In
      contrast, when deciding on the introduction of a new vaccine into a national
      immunization program or on a recommendation for a specific risk-group, the focus
      is shifted to considerations of how a licensed vaccine can be best used in a
      population (e.g., which immunization strategy is most effective in preventing
      deaths or hospitalizations, or in reducing treatment costs for the health care
      system). Stringent assessment criteria have been developed that require a robust
      safety analysis before a new vaccine is administered to humans for the first time
      in pre-licensure studies. Similarly, criteria are applied for calculating the
      benefit-risk ratio at the time of the licensure of a new vaccine in addition to
      during the entire post-licensure period. However, when deciding if and how a
      licensed vaccine can best be integrated into an existing immunization program,
      additional criteria are applied that are different, yet complementary to those
      applied for granting a marketing authorization. These decisions require-in
      addition to considerations of vaccine quality, vaccine efficacy and safety
      conclusions regarding population-level effects combined with an integrative
      analysis of the local context (e.g., local epidemiology, cost-effectiveness, and
      acceptance by the population). To serve these objectives, national authorities
      such as the Standing Committee on Vaccination in Germany (STIKO) have been
      established to integrate globally developed vaccines into the national context of
      immunization strategies. 

PMID- 25566842
TI  - [Benefit assessment of drugs].
AB  - In Germany, new drugs are subject to a benefit assessment at the time of their
      market access. This "early benefit assessment" is the method primarily used for
      the benefit assessment of pharmaceuticals in Germany. While for the authorization
      of a drug a positive risk-benefit ratio is sufficient, early benefit assessment
      examines whether the new drug has an added benefit compared with other therapies,
      and thus differs significantly from authorization. For the evaluation, the
      manufacturer is required to submit a dossier, which must contain all the relevant
      studies. Early benefit assessment is very transparent in international
      comparisons, because all the relevant data and the evaluation report will be
      published. The assessment is carried out with regard to the evidence-based
      standard of care (the "appropriate comparator"). If the new drug is found to have
      an additional benefit, the extent of this added benefit is assessed. In addition,
      groups of patients should be identified with the particular extent of the added
      benefit. Therefore, subgroup analyses have to be carried out frequently. Often,
      for new drugs, only registration studies are available. General requirements for
      such studies (e.g., placebo comparison, endpoints) and decisions regarding the
      approval process (e.g., dosage regimens) can affect the level of confidence of
      these studies in the benefit assessment. Joint scientific advice by regulatory
      authorities and HTA (health technology assessment) agencies are provided to solve
      this problem. However, this is not possible without additional expense for the
      pharmaceutical companies. 

PMID- 25566843
TI  - [Benefit assessment of medical devices].
AB  - Medical devices play an important role in both the diagnostic and therapeutic
      care of patients. The hope is that particularly innovative medical devices can
      contribute to the improvement of patient care. However, there is no mandatory
      need to conduct clinical studies with medical devices that allow an assessment of
      their benefit within the framework of EU market access or on the way to
      reimbursement by the statutory health insurance (SHI) in Germany. Numerous
      examples show that the existing legal framework for market access and for
      reimbursement in the SHI system is insufficient for providing patients with only
      those examination and treatment methods, i. e., medical devices, that comply with
      the benefit requirement and the imperative for quality stipulated in the Social
      Code Book V. However, it is possible to conduct meaningful clinical trials, i.
      e., randomized controlled trials, with medical devices as well. Hence, regular,
      indication-related benefit assessment of medical devices with a higher risk class
      as a prerequisite for reimbursement for a specific medical device is not only
      necessary, but also feasible. The 2014 report of the Advisory Council on the
      Assessment of Developments in the Healthcare System contains a promising
      recommendation for implementing this. A regulatory framework as described in the
      report would allow patients the fastest possible access to safe and effective
      medical device innovations, while increasing planning reliability for the
      development and marketing of new products, which has often been criticized as
      insufficient by manufacturers. 

PMID- 25566844
TI  - [Benefit assessment of operative interventions from the perspective of surgical
      research].
AB  - The benefit assessment of surgical procedures serves as the basis for the concept
      of evidence-based surgery. However, especially in the field of surgery, many
      interventions are lacking assessment in high-quality clinical trials. Therefore,
      a well-structured benefit assessment of surgical interventions in the future is
      imperative. Considering the different perspectives, e.g. of the patients,
      surgeons, industry or health care investors, the implications of the benefits and
      risks of a procedure can differ significantly. Researchers have to abide by
      different regulations, depending on the type of intervention being evaluated in a
      surgical trial. Furthermore, the benefit assessment of surgical procedures poses
      specific challenges, from the choice of a relevant endpoint to issues concerning
      the standardization of the interventions and the impact of learning curves. The
      IDEAL concept, which was established by a group of international experts in 2009,
      serves as a framework for the future development and assessment of innovations in
      the field of surgery. For example, the SDGC (Study Center of the German Society
      of Surgery) and CHIR-Net (Surgical Studies Network) indicate that such
      collaborations of clinicians and methodologists can lead to the creation of a
      qualified structure for the effective benefit assessment of surgical procedures.
      In the future, the aforementioned evidence gaps must be eliminated and
      innovations evaluated efficiently by the work of such networks. 

PMID- 25566845
TI  - [Update on outbreaks reported from neonatal intensive care units (2010-203):
      Staphylococcus aureus].
AB  - In terms of the unique risk profile of the patients and the morbidity associated
      with S. aureus infections in this vulnerable patient population, the literature
      on outbreaks of S. aureus (including MRSA) in neonatal intensive care units
      (NICUs) needs to be analyzed separately from reports derived from other intensive
      care units. With the objective of updating important information for those
      involved in outbreak management and fostering preventive efforts, this article
      summarizes the results of a systematic literature analysis, referring to an
      earlier publication by Gastmeier et al. It focuses on NICU outbreaks caused by S.
      aureus (including MRSA) and on controlling them. 

PMID- 25566846
TI  - [The German Pharmaceutical Market Reorganization Act (AMNOG) from an economic
      point of view].
AB  - Since the introduction of early benefit assessments in Germany, prices for new
      medicinal products are set in accordance with the "degree of additional benefit."
      The major aim of the present work is to point out the economic rationale for the
      definition of a regulatory price for patent-protected drugs. With regard to the
      economic objectives of efficient allocation of resources, reducing information
      asymmetries, and promoting high-value innovation, the applied benefit assessments
      represent major progress in the German health care sector. In addition to the
      multifaceted criticism of procedural details, there is a general risk that the
      institutions involved are lagging behind societal preferences. In this case,
      early benefit assessments may lead to suboptimal results. The pharmaceutical
      industry's ability to innovate, on the other hand, may be seen to be a result of
      the interaction between national benefit assessments and the research activities
      of internationally oriented drug manufacturers. Accordingly, recent trends toward
      the implementation of national early benefit assessments in combination with
      international reference pricing may be seen to be critical; however, Germany is
      merely following the trend of other countries. 

PMID- 25566848
TI  - Tuning the pore sizes of novel silica membranes for improved gas permeation
      properties via an in situ reaction between NH3 and Si-H groups.
AB  - A new concept was proposed to control the pore size in a novel silica membrane.
      The tuning of the pore sizes in triethoxysilane (TRIES)-derived membranes was
      successfully conducted via an in situ reaction between NH3 and Si-H groups at
      high temperatures. The formation of Si-NH2 and/or Si-NH groups in the silica
      structure enhanced the hydrogen selectivity. 

PMID- 25566849
TI  - 1,4-Bis(2'-pyridylethynyl)benzene as a ligand in heteronuclear gold-thallium
      complexes. Influence of the ancillary ligands on their optical properties.
AB  - The reaction of 1,4-bis(2'-pyridylethynyl)benzene (L) with [{Au(C6X5)2}Tl]n
      affords new heterometallic Au(I)/Tl(I) complexes with different stoichiometries,
      structural arrangements and optical properties depending on the halogens present
      in the aryl group. The chlorinated derivative [{Au(C6Cl5)2}Tl(L)]n () displays
      polymeric chains built thanks to unsupported AuTl interactions and bridging
      bidentate ligands between adjacent chains, while in the fluorinated species
      [{Au(C6F5)2}2Tl2(L)2]n (), also containing N-donor bridging ligands and AuTl
      contacts, polymerization occurs via TlCaryl non-bonding interactions between
      neighbouring molecules. The optical properties of and have been studied
      experimentally and theoretically, concluding that the luminescence of in the
      solid state has its origin in the AuTl interactions, and that the TlCaryl
      interactions in favour a non-radiative deactivation pathway that avoids
      luminescence. The strength of the non-bonding interactions present in has also
      been theoretically studied at the HF and MP2 levels, revealing the metallophilic
      contact as the strongest one. 

PMID- 25566847
TI  - Age and gender related neuromuscular changes in trunk flexion-extension.
AB  - BACKGROUND: The root mean square surface electromyographic activity of lumbar
      extensor muscles during dynamic trunk flexion and extension from a standing
      position and task specific spine ranges of motion objectively assess muscle
      function in healthy young and middle age individuals. However, literature on
      neuromuscular activation and associated spine and hip kinematics in older
      individuals is sparse. This cross sectional study sought to examine the sex and
      age (<40 versus >60 years) related differences in the neuromuscular activation
      profiles of the lumbar extensors and the related spine and hip kinematics from
      healthy individuals during a standardized trunk flexion-extension task. METHODS:
      Twenty five older (13 females, 60-90 years) and 24 younger (12 females, 18-40
      years) healthy individuals performed trunk flexion-extension testing by holding
      static positions at half-flexion way and full range of motion between standing
      and maximum trunk flexion. The associated lumbar extensor muscle activity was
      derived from measurements at standing, half, and maximum flexion positions. The
      range of motion at the hip and lumbar spine was recorded using 3d accelerometers
      attached to the skin overlying the multifidus and semispinalis thoracis muscles
      lateral to the L5 and T4 spinous processes, respectively. Statistical
      calculations were performed using a permutation ANOVA with bootstrap confidence
      intervals. RESULTS: The muscle activity in the half related to the maximum
      flexion position (half flexion relaxation ratio) was significantly smaller in
      older males when compared with younger males. Moreover, measurements revealed
      smaller activity changes from standing to the half and from half to the maximum
      flexion position in older compared to younger individuals. Older males displayed
      smaller gross trunk range of motion from standing to maximum flexion than any
      other group. CONCLUSIONS: Gender and normal aging significantly affect both the
      activation patterns of the lumbar extensor muscles and the kinematics of the
      trunk during a standardized trunk flexion-extension task. Measurement results
      from healthy young and middle age individuals should not be used for the
      assessment of individuals older than 60 years of age.

PMID- 25566850
TI  - Tuning viscoelastic properties of supramolecular peptide gels via dynamic
      covalent crosslinking.
AB  - A dynamic covalent crosslinking approach is used to crosslink supramolecular
      peptide gels. This novel approach facilitates tuning viscoelastic properties of
      the gel and enhances mechanical stability (storage modulus exceeding 10(5) Pa) of
      the peptide gels. 

PMID- 25566851
TI  - Design rules for metal binding biomolecules: understanding of amino acid
      adsorption on platinum crystallographic facets from density functional
      calculations.
AB  - Understanding the mechanism of biomolecules' interaction with inorganic surfaces
      might pave the way for the design of material interfaces with controlled and
      highly predictable properties. Here we have focused on the adsorption mechanism
      of facet-specific amino acids in the sequence of peptides selected for programmed
      synthesis of Pt(111) and Pt(100) nanocrystals. Using the first principles
      calculations we have demonstrated that the specific surface recognition of amino
      acid side chains occurs due to the combination of multiple processes: electron
      exchange, partial charge transfer and/or dispersive effects providing a high
      binding affinity to both polar and non-polar residues against both Pt facets. Our
      approach points towards promising novel routes for controlled design of material
      specific linkers for future materials engineering. 

PMID- 25566852
TI  - A near-infrared light-controlled system for reversible presentation of bioactive
      ligands using polypeptide-engineered functionalized gold nanorods.
AB  - A near-infrared light-controlled hybrid platform with polypeptide-engineered
      functionalized gold nanorods has been designed for reversible presentation of the
      immobilized ligands to cell surface receptors on the engineered materials. 

PMID- 25566854
TI  - Dissection of the genetic architecture underlying the plant density response by
      mapping plant height-related traits in maize (Zea mays L.).
AB  - Plant height is one of the most heritable traits in maize (Zea mays L.).
      Understanding the genetic control of plant height is important for elucidating
      the molecular mechanisms that regulate maize development. To investigate the
      genetic basis of the plant height response to density in maize, we evaluated the
      effects of two different plant densities (60,000 and 120,000 plant/hm(2)) on
      three plant height-related traits (plant height, ear height, and ear height-to
      plant height ratio) using four sets of recombinant inbred line populations. The
      phenotypes observed under the two-plant density treatments indicated that high
      plant density increased the phenotypic performance values of the three measured
      traits. Twenty-three quantitative trait loci (QTLs) were detected under the two
      plant density treatments, and five QTL clusters were located. Nine QTLs were
      detected under the low plant density treatment, and seven QTLs were detected
      under the high plant density treatment. Our results suggested that plant height
      may be controlled mainly by a common set of genes that could be influenced by
      additional genetic mechanisms when the plants were grown under high plant
      density. Fine mapping for genetic regions of the stable QTLs across different
      plant density environments may provide additional information about their
      different responses to density. The results presented here provide useful
      information for further research and will help to reveal the molecular mechanisms
      related to plant height in response to density.

PMID- 25566855
TI  - A self-assembled nanopatch with peptide-organic multilayers and mechanical
      properties.
AB  - Peptides enable the construction of a diversity of one-dimensional (1D) and zero
      dimensional (0D) nanostructures by molecular self-assembly. To date, it is a
      great challenge to construct two-dimensional (2D) nanostructures from peptides.
      Here we introduce an organic molecule to tune the amphiphilic-like peptide
      assembly to form a peptide-organic 2D nanopatch structure. The nanomechanical
      properties of the nanopatch were explored by quantitative nanomechanical imaging
      and force control manipulation. The peptide-organic patches are multilayers
      composed of several domains, which can be peeled off stepwise. The patch
      formation provides an approach towards constructing 2D nanostructures by peptide
      organic assembly and it could be potentially utilized in a wide range of
      applications such as functional biomaterials. 

PMID- 25566853
TI  - Evaluation of miRNA-binding-site SNPs of MRE11A, NBS1, RAD51 and RAD52 involved
      in HRR pathway genes and risk of breast cancer in China.
AB  - MiRNA-binding-site single nucleotide polymorphisms (SNPs) in homologous
      recombination repair (HRR) pathway genes may change DNA repair capacity and
      affect susceptibility to cancer though complex gene-gene and gene-reproductive
      factors interactions. However, these SNPs associated with breast cancer (BC) are
      still unclear in Chinese women. Therefore, we conducted a case-control study to
      evaluate the genetic susceptibility of the five miRNA-binding-site SNPs in HRR
      pathway genes (MRE11A rs2155209, NBS1 rs2735383, RAD51 rs963917 and rs963918 and
      RAD52 rs7963551) in the development of BC. MRE11A rs2155209 and RAD52 rs7963551
      were found to be associated with BC risk (ORadjusted: 1.87; 95 % CI: 1.23-2.86
      and ORadjusted: 0.36; 95 % CI: 0.24-0.58). NBS1 rs2735383, RAD51 rs963917 and
      rs963918 were associated with BC risk after stratification according to
      reproductive factors. Haplotypes of Crs963917Ars963918 decreased the risk of BC
      (ORadjusted: 0.53; 95 % CI: 0.4-0.68), while the Trs963917Ars963918 and
      Trs963917Grs963918 haplotypes could increase the risk of BC (ORadjusted: 1.28; 95
      % CI: 1.05-1.57 and ORadjusted: 1.31; 95 % CI: 1.09-1.62). Combined effect of
      risk alleles showed that the five SNPs were associated with increased BC risk in
      a dose-dependent manner (P trend = 0.003). The GC genotype of rs2735383, AG + GG
      genotype of rs963918 and AC + CC genotype of rs7963551 were associated with PR
      positivity of BC patients. These findings suggest that the miRNA-binding-site
      SNPs involved in HRR pathway genes may affect susceptibility of BC in Chinese
      women; moreover, the interactions of gene-gene and gene-reproductive factors play
      vital roles in the progression of BC. Further functional studies with larger
      sample are needed to support and validate these findings. 

PMID- 25566856
TI  - Ethanol induces the formation of water-permeable defects in model bilayers of
      skin lipids.
AB  - We show that ethanol can induce the formation of water-permeable defects in model
      membranes of skin, providing a fresh perspective on ethanol as a membrane
      modulator. We rationalise our findings in terms of the chemical nature of
      ethanol, i.e., a combination of its hydrogen bonding propensity and amphiphilic
      character. 

PMID- 25566857
TI  - Risk and prognosis of Staphylococcus aureus bacteremia among individuals with and
      without end-stage renal disease: a Danish, population-based cohort study.
AB  - BACKGROUND: Staphylococcus aureus is a leading cause of bloodstream infections
      among hemodialysis patients and of exit-site infections among peritoneal dialysis
      patients. However, the risk and prognosis of Staphylococcus aureus bacteremia
      among end-stage renal disease patients have not been delineated. METHODS: In this
      Danish nationwide, population-based cohort study patients with end-stage renal
      disease and matched population controls were observed from end-stage renal
      disease diagnosis/sampling until first episode of Staphylococcus aureus
      bacteremia, death, or end of study period. Staphylococcus aureus positive blood
      cultures, hospitalization, comorbidity, and case fatality were obtained from
      nationwide microbiological, clinical, and administrative databases. Incidence
      rates and risk factors were assessed by regression analysis. RESULTS: The
      incidence rate of Staphylococcus aureus bacteremia was very high for end-stage
      renal disease patients (35.7 per 1,000 person-years; 95% CI, 33.8-37.6) compared
      to population controls (0.5 per 1,000 person-years; 95% CI, 0.5-0.6), yielding a
      relative risk of 65.1 (95% CI, 59.6-71.2) which fell to 28.6 (95% CI, 23.3-35.3)
      after adjustment for sex, age, and comorbidity. After stratification for type of
      renal replacement therapy, we found the highest incidence rate of Staphylococcus
      aureus bacteremia among hemodialysis patients (46.3 per 1,000 person-years)
      compared to peritoneal dialysis patients (22.0 per 1,000 person-years) and renal
      transplant recipients (8.9 per 1,000 person-years). In persons with
      Staphylococcus aureus bacteremia, ninety-day case fatality was 18.2% (95% CI,
      16.2%-20.3%) for end-stage renal disease patients and 33.7% (95% CI, 30.3-37.3)
      for population controls. CONCLUSIONS: Patients with end-stage renal disease, and
      hemodialysis patients in particular, have greatly increased risk of
      Staphylococcus aureus bacteremia compared to population controls. Future
      challenges will be to develop strategies to reduce Staphylococcus aureus
      bacteremia-related morbidity and death in this high-risk population.

PMID- 25566858
TI  - In vitro and in vivo evaluation of the developed PLGA/HAp/Zein scaffolds for bone
      cartilage interface regeneration.
AB  - OBJECTIVE: To investigate the effect of electronspun PLGA/HAp/Zein scaffolds on
      the repair of cartilage defects. METHODS: The PLGA/HAp/Zein composite scaffolds
      were fabricated by electrospinning method. The physiochemical properties and
      biocompatibility of the scaffolds were separately characterized by scanning
      electron microscope (SEM), transmission electron microscope (TEM), and fourier
      transform infrared spectroscopy (FTIR), human umbilical cord mesenchymal stem
      cells (hUC-MSCs) culture and animal experiments. RESULTS: The prepared
      PLGA/HAp/Zein scaffolds showed fibrous structure with homogenous distribution.
      hUC-MSCs could attach to and grow well on PLGA/HAp/Zein scaffolds, and there was
      no significant difference between cell proliferation on scaffolds and that
      without scaffolds (P>0.05). The PLGA/HAp/Zein scaffolds possessed excellent
      ability to promote in vivo cartilage formation. Moreover, there was a large
      amount of immature chondrocytes and matrix with cartilage lacuna on PLGA/HAp/Zein
      scaffolds. CONCLUSION: The data suggest that the PLGA/HAp/Zein scaffolds possess
      good biocompatibility, which are anticipated to be potentially applied in
      cartilage tissue engineering and reconstruction.

PMID- 25566859
TI  - Microwave exposure impairs synaptic plasticity in the rat hippocampus and PC12
      cells through over-activation of the NMDA receptor signaling pathway.
AB  - OBJECTIVE: The aim of this study is to investigate whether microwave exposure
      would affect the N-methyl-D-aspartate receptor (NMDAR) signaling pathway to
      establish whether this plays a role in synaptic plasticity impairment. METHODS:
      48 male Wistar rats were exposed to 30 mW/cm2 microwave for 10 min every other
      day for three times. Hippocampal structure was observed through H&E staining and
      transmission electron microscope. PC12 cells were exposed to 30 mW/cm2 microwave
      for 5 min and the synapse morphology was visualized with scanning electron
      microscope and atomic force microscope. The release of amino acid
      neurotransmitters and calcium influx were detected. The expressions of several
      key NMDAR signaling molecules were evaluated. RESULTS: Microwave exposure caused
      injury in rat hippocampal structure and PC12 cells, especially the structure and
      quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid
      neurotransmitters was increased and the intracellular calcium level was elevated
      in PC12 cells. A significant change in NMDAR subunits (NR1, NR2A, and NR2B) and
      related signaling molecules (Ca2+/calmodulin-dependent kinase II gamma and
      phosphorylated cAMP-response element binding protein) were examined. CONCLUSION:
      30 mW/cm2 microwave exposure resulted in alterations of synaptic structure, amino
      acid neurotransmitter release and calcium influx. NMDAR signaling molecules were
      closely associated with impaired synaptic plasticity.

PMID- 25566860
TI  - Rapid detection of rifampin-resistant clinical isolates of Mycobacterium
      tuberculosis by reverse dot blot hybridization.
AB  - OBJECTIVE: A PCR-reverse dot blot hybridization (RDBH) assay was developed for
      rapid detection of rpoB gene mutations in 'hot mutation region' of Mycobacterium
      tuberculosis (M. tuberculosis). METHODS: 12 oligonucleotide probes based on the
      wild-type and mutant genotype rpoB sequences of M. tuberculosis were designed to
      screen the most frequent wild-type and mutant genotypes for diagnosing RIF
      resistance. 300 M. tuberculosis clinical isolates were detected by RDBH,
      conventional drug-susceptibility testing (DST) and DNA sequencing to evaluate the
      RDBH assay. RESULTS: The sensitivity and specificity of the RDBH assay were 91.2%
      (165/181) and 98.3% (117/119), respectively, as compared to DST. When compared
      with DNA sequencing, the accuracy, positive predictive value (PPV) and negative
      predictive value (NPV) of the RDBH assay were 97.7% (293/300), 98.2% (164/167),
      and 97.0% (129/133), respectively. Furthermore, the results indicated that the
      most common mutations were in codons 531 (48.6%), 526 (25.4%), 516 (8.8%), and
      511 (6.6%), and the combinative mutation rate was 15 (8.3%). One and two strains
      of insertion and deletion were found among all strains, respectively. CONCLUSION:
      Our findings demonstrate that the RDBH assay is a rapid, simple and sensitive
      method for diagnosing RIF-resistant tuberculosis.

PMID- 25566861
TI  - Cytoprotective effect of silymarin against diabetes-induced cardiomyocyte
      apoptosis in diabetic rats.
AB  - OBJECTIVE: The beneficial effects of silymarin have been extensively studied in
      the context of inflammation and cancer treatment, yet much less is known about
      its therapeutic effect on diabetes. The present study was aimed to investigate
      the cytoprotective activity of silymarin against diabetes-induced cardiomyocyte
      apoptosis. METHODS: Rats were randomly divided into: control group, untreated
      diabetes group and diabetes group treated with silymarin (120 mg/kg*d) for 10 d.
      Rats were sacrificed, and the cardiac muscle specimens and blood samples were
      collected. The immunoreactivity of caspase-3 and Bcl-2 in the cardiomyocytes was
      measured. Total proteins, glucose, insulin, creatinine, AST, ALT, cholesterol,
      and triglycerides levels were estimated. RESULTS: Unlike the treated diabetes
      group, cardiomyocyte apoptosis increased in the untreated rats, as evidenced by
      enhanced caspase-3 and declined Bcl-2 activities. The levels of glucose,
      creatinine, AST, ALT, cholesterol, and triglycerides declined in the treated
      rats. The declined levels of insulin were enhanced again after treatment of
      diabetic rats with silymarin, reflecting a restoration of the pancreatic beta
      cells activity. CONCLUSION: The findings of this study are of great importance,
      which confirmed for the first time that treatment of diabetic subjects with
      silymarin may protect cardiomyocytes against apoptosis and promote survival
      restoration of the pancreatic beta-cells.

PMID- 25566862
TI  - The pollution character analysis and risk assessment for metals in dust and PM10
      around road from China.

PMID- 25566863
TI  - Bone injury and fracture healing biology.

PMID- 25566864
TI  - Pathological changes in the sinoatrial node tissues of rats caused by pulsed
      microwave exposure.
AB  - To observe microwave induced dynamic pathological changes in the sinus nodes,
      wistar rats were exposed to 0, 5, 10, 50 mW/cm2 microwave. In 10 and 50 mW/cm2
      groups, disorganized sinoatrial node cells, cell swelling, cytoplasmic
      condensation, nuclear pyknosis, and anachromasis, swollen, and empty
      mitochondria, and blurred and focally dissolved myofibrils could be detected from
      1 to 28 d, while reduced parenchymal cells, increased collagen fibers, and
      extracellular matrix remodeling of interstitial cells were observed from 6 to 12
      months. In conclusion, 10 and 50 mW/cm2 microwave could cause structural damages
      in the sinoatrial node and extracellular matrix remodeling in rats. 

PMID- 25566865
TI  - Ambient temperature and outpatient visits for acute exacerbation of chronic
      bronchitis in Shanghai: a time series analysis.
AB  - The association between ambient temperature and acute exacerbation of chronic
      bronchitis (AECB) was still unknown. Therefore, we performed an epidemiological
      study in a large hospital of Shanghai to explore the relationship about
      temperature and outpatient visit for AECB. We adopted a quasi-Poisson generalized
      additive models and distributed lag nonlinear models to estimate the accumulative
      effects of temperature on AECB across multiple days. We found significant non
      linear effects of cold temperature on hospital visits for AECB, and the potential
      effect of cold temperature might last more than 2 weeks. The relative risks of
      extreme cold (first percentiles of temperature throughout the study period) and
      cold (10th percentile of temperature) temperature over lags 0-14 d were 2.98 [95%
      confidence intervals (CI): 1.77, 5.04] and 1.63 (95% CI: 1.21, 2.19), compared
      with the 25th percentile of temperature. However, we found no positive
      association between hospital visits and hot weather. This study showed that
      exposure to both extreme cold and cold temperatures were associated with
      increased outpatient visits for AECB in a large hospital of Shanghai. 

PMID- 25566866
TI  - Assessing the effectiveness of a cervical cancer screening program in a hospital
      based study.
AB  - To study the microbiological contamination of kitchen dishcloths in Chinese
      housholds, 1010 'in-use' kitchen dishcloths were collected from residential
      premises in Beijing and Shanghai, and they were sent to the laboratory for
      microbiological quality analysis. The aerobic plate counts for dishcloths were 10
      109 cfu/cm2 in the range of 150 cfu/cm2 to 1.776*109 cfu/cm2 (Beijing) and 62.5
      cfu/cm2 to 8.75*108 cfu/cm2 (Shanghai). Nineteen species of bacteria were
      detected in the dishcloths, most of which were conditional pathogenic bacteria.
      This study found a significant difference in the aerobic plate counts of
      dishcloths with regard to type, number of the days used, activities used for, and
      some family factors. The findings of the study highlight the potential for
      contamination of kitchen dishcloths within homes. 

PMID- 25566867
TI  - In vivo digestive stability of soybean beta-conglycinin beta-subunit in WZS
      minipigs.
AB  - By now, the digestive stability experiments provided by most authoritative
      organizations are in vitro tests. Evaluating the protein digestive stability with
      in vivo models should be more objective. The present study aimed to verify the in
      vivo digestibility of soybean beta-conglycinin beta-subunit in Wuzhishan (WZS)
      minipigs. Three minipigs were surgically fitted with O-stomach and T-ileum
      cannulae and fed with soybean meals. According to SDS-PAGE, the 50 kD fraction of
      soybean beta-conglycinin beta-subunit persisted in the gastric fluid until 6 h
      after feeding, which was detected at 3 h and clearly visible at 4-6 h in the
      intestinal fluid. Western blot with anti-beta-conglycinin beta-subunit McAb
      confirmed it. 

PMID- 25566868
TI  - Temperature dependence of the thermopower and its variation of the Au atomic
      contact.
AB  - We performed simultaneous measurements of the thermopower, and conductance of Au
      atomic contacts during the self-breaking process under temperature control.
      During the whole measurement temperature regime (290-330 K), the thermopower
      randomly fluctuated from positive to negative in sign, and the average
      thermopower was negligibly small with respect to the variation of the thermopower
      of the contact. Meanwhile, the standard deviation of the thermoelectric voltage
      increased linearly with the temperature difference across the contacts. Above 320
      K, we observed a decrease in the standard deviation of thermopower, which
      suggested a decrease in the density of defects near the contacts. The linear
      increase in the standard deviation of the thermoelectric voltage, and the
      decrease in the standard deviation of the thermopower above 320 K, indicate that
      the standard deviation of thermopower provides insight into the thermopower of an
      individual Au atomic contact and the atomic structure of Au atomic contacts, such
      as crystallinity and the distribution of defects near the contacts. 

PMID- 25566869
TI  - Analysis of motion of the rectum during preoperative intensity modulated
      radiation therapy for rectal cancer using cone-beam computed tomography.
AB  - PURPOSE: The purpose of the present study was to quantify the inter-fractional
      motion of the rectum and the rectal and bladder volumes using CBCT scans taken
      during chemoradiation therapy (CRT) for rectal cancer. Also, assessment was made
      for a better margin for simultaneous integrated boost - intensity modulated
      radiation therapy (SIB-IMRT) for rectal cancer. METHODS AND MATERIALS: There were
      32 patients in this study undergoing preoperative CRT for rectal cancer. Each
      rectum and bladder was contoured on all planning CTs and CBCTs (day 1, 7, 13, 19,
      25). The target volume was configured by adding margins (0, 3, 5, 7, 10, and 15
      mm) to the rectum on planning CT. The respective percentage of rectal volume that
      exceeds the target volume was calculated for each of these margins. The
      percentage of bladder volume that exceeds the bladder volume in the planning CT
      and motion of the center of gravity of rectum were also analyzed. RESULTS:
      Planning CTs and series of each 5 CBCTs for 32 patients were analyzed in this
      study. The rectal volume tended to shrink week after week. The mean values (+/-
      SD) in the 32 series per patient of the percentage of rectum on the CBCTs
      exceeding target volume in which the margins of 0, 3, 5, 7, 10, and 15 mm were
      added to the rectum on planning CT were 20.7 +/- 12.5%, 7.2 +/- 8.3%, 3.9 +/-
      5.9%, 2.1 +/- 3.9%, 0.7 +/- 1.8%, and 0.1 +/- 0.3%, respectively. No association
      was seen between the percentage of changes of bladder volume and motion of rectal
      centroid. CONCLUSIONS: In this study, we estimated the motion of the rectum using
      planning CT and CBCT. Ten to fifteen mm is a sufficient margin for the rectum
      during SIB-IMRT for rectal cancer in the supine position.

PMID- 25566870
TI  - The high-affinity human IgG receptor Fc gamma receptor I (FcgammaRI) is not
      associated with vascular leakage of dengue.
AB  - BACKGROUND: Dengue is a major public health problem in many tropical and sub
      tropical countries. Vascular leakage and shock are identified as the major causes
      of deaths in patients with severe dengue. Studies have suggested the potential
      role of Fc gamma receptors I (FcgammaRI) in the pathogenesis of dengue. We
      hypothesized that the circulating level of Fcgamma receptor I could potentially
      be used as an indicator in assisting early diagnosis of severe dengue. RESULTS: A
      selected cohort of 66 dengue patients including 42 dengue with signs of vascular
      leakage, and 24 dengue without signs of vascular leakage were identified and were
      afterwards referred to as 'cases' and 'controls' respectively. Thirty seven
      normal healthy controls were also recruited in this study. The circulating level
      of FcgammaRI was quantified from the serum using enzyme-link immunosorbent assay
      (ELISA). The levels of FcgammaRI in both groups of patients with and without
      vascular leakage were found to be significantly higher than the normal healthy
      controls (P < 0.001). However, there was no significant difference found between
      patients with vascular leakage and those without vascular leakage (p = 0.777).
      CONCLUSION: We suggest that FcgammaRI is not associated with the vascular leakage
      in dengue. However, further studies are necessary to delineate the role of
      FcgammaRI in antibody-dependent enhancement (ADE) mechanism.

PMID- 25566871
TI  - A conserved P-loop anchor limits the structural dynamics that mediate nucleotide
      dissociation in EF-Tu.
AB  - The phosphate-binding loop (P-loop) is a conserved sequence motif found in
      mononucleotide-binding proteins. Little is known about the structural dynamics of
      this region and its contribution to the observed nucleotide binding properties.
      Understanding the underlying design principles is of great interest for
      biomolecular engineering applications. We have used rapid-kinetics measurements
      in vitro and molecular dynamics (MD) simulations in silico to investigate the
      relationship between GTP-binding properties and P-loop structural dynamics in the
      universally conserved Elongation Factor (EF) Tu. Analysis of wild type EF-Tu and
      variants with substitutions at positions in or adjacent to the P-loop revealed a
      correlation between P-loop flexibility and the entropy of activation for GTP
      dissociation. The same variants demonstrate more backbone flexibility in two N
      terminal amino acids of the P-loop during force-induced EF-Tu . GTP dissociation
      in Steered Molecular Dynamics simulations. Amino acids Gly18 and His19 are
      involved in stabilizing the P-loop backbone via interactions with the adjacent
      helix C. We propose that these P-loop/helix C interactions function as a
      conserved P-loop anchoring module and identify the presence of P-loop anchors
      within several GTPases and ATPases suggesting their evolutionary conservation.

PMID- 25566872
TI  - Rapid synthesis of monodisperse Au nanospheres through a laser irradiation
      induced shape conversion, self-assembly and their electromagnetic coupling SERS
      enhancement.
AB  - We develop a facile and effective strategy to prepare monodispersed Au spherical
      nanoparticles by two steps. Large-scale monocrystalline Au nanooctahedra with
      uniform size were synthesized by a polyol-route and subsequently Au nanoparticles
      were transformed from octahedron to spherical shape in a liquid under ambient
      atmosphere by non-focused laser irradiation in very short time. High
      monodispersed, ultra-smooth gold nanospheres can be obtained by simply optimizing
      the laser fluence and irradiation time. Photothermal melting-evaporation model
      was employed to get a better understanding of the morphology transformation for
      the system of nanosecond pulsed-laser excitation. These Au nanoparticles were
      fabricated into periodic monolayer arrays by self-assembly utilizing their high
      monodispersity and perfect spherical shape. Importantly, such Au nanospheres
      arrays demonstrated very good SERS enhancement related to their periodic
      structure due to existence of many SERS hot spots between neighboring Au
      nanospheres caused by the electromagnetic coupling in an array. These gold
      nanospheres and their self-assembled arrays possess distinct physical and
      chemical properties. It will make them as an excellent and promising candidate
      for applying in sensing and spectroscopic enhancement, catalysis, energy, and
      biology.

PMID- 25566873
TI  - Impaired endogenous fibrinolytic capacity in prehypertensive men.
AB  - Prehypertension (blood pressure (BP) 120-139/80-89 mm Hg) is associated with an
      increased risk for future atherothrombotic events. Although the mechanisms
      underlying this elevated risk are not completely understood, one possibility is
      that prehypertension is associated with impaired endothelial fibrinolytic
      capacity. We tested the hypothesis that vascular endothelial release of tissue
      type plasminogen activator (t-PA) is impaired in prehypertensive men. Net
      endothelial release of t-PA was determined, in vivo, in response to intrabrachial
      infusions of bradykinin (12.5, 25, 50 ng per 100 ml tissue per min) and sodium
      nitroprusside at (1.0, 2.0, 4.0 MUg per 100 ml tissue per min) in 42 middle-age
      and older men: 16 normotensive (BP range: 100-119/57-79 mm Hg); 16
      prehypertensive (BP range: 120-139/76-89 mm Hg); and 10 hypertensive (BP range:
      140-150/74-100 mm Hg). Net release of t-PA antigen was ~25% lower (P<0.05) in the
      prehypertensive (-0.9 +/- 0.8 to 42.4 +/- 5.3 ng per 100 ml tissue per min)
      compared with the normotensive (0.5 +/- 1.0 to 53.9 +/- 6.5 ng per 100 ml tissue
      per min) men. There was no significant difference in t-PA release between the
      hypertensive (-1.8 +/- 1.6 to 40.8 +/- 6.6 ng per 100 ml tissue per min) and
      prehypertensive groups. Sodium nitroprusside did not significantly alter the t-PA
      release in any group. These data indicate that endothelial t-PA release is
      diminished in prehypertensive men. Further, the level of impairment in t-PA
      release seen with clinical hypertension is already apparent in the
      prehypertensive state. Impaired endothelial fibrinolytic function may underlie
      the increased atherothrombotic risk associated with BP in the prehypertensive
      range.

PMID- 25566875
TI  - It is time to contend with the endothelial consequences of prehypertension.

PMID- 25566874
TI  - Performance and persistence of a blood pressure self-management intervention:
      telemonitoring and self-management in hypertension (TASMINH2) trial.
AB  - This study aimed to evaluate, in detail, the implementation of the self
      management intervention used in the TASMINH2 trial. The intervention, comprising
      self-monitoring for the first week of each month and an individualised treatment
      self-titration schedule, was developed from a previous trial of self-management.
      Two hundred and sixty-three patients with poorly controlled but treated
      hypertension were randomised to receive this intervention and underwent training
      over two or three sessions. Participants were followed up for 12 months during
      which time process data were collected regarding the persistence and fidelity of
      actual behaviour compared with intervention recommendations. Two hundred and
      forty-one (92%) patients completed training of whom 188 (72%) self-managed their
      BP and completed at least 90% of expected self-monitoring measurements for the
      full year of the study. Overall, 268/483 (55%) of recommended medication changes
      were implemented. Only 25 (13%) patients had controlled BP throughout the year
      and so were not recommended any medication changes. Adherence to the protocol
      reduced over time as the number of potential changes increased. Of those self
      managing throughout, 131 (70%) made at least one medication change, with 77 (41%)
      implementing all their recommended changes. In conclusion, self-management of
      hypertension was possible in practice with most participants making at least one
      medication change. Although adherence to the intervention reduced over time,
      implementation of treatment recommendations appeared better than equivalent
      trials using physician titration. Future self-management interventions should aim
      to better support patients' decision making, perhaps through enhanced use of
      technology. 

PMID- 25566877
TI  - Thermo-sensitive nanoparticles for triggered release of siRNA.
AB  - Efficient delivery of small interfering RNA (siRNA) is crucially required for
      cancer gene therapy. Herein, a thermo-sensitive copolymer with a simple
      structure, poly (ethylene glycol) methyl ether acrylate-b-poly (N
      isopropylacrylamide) (mPEG-b-PNIPAM) was developed. A novel kind of thermo
      sensitive nanoparticles (DENPs) was constructed for the cold-shock triggered
      release of siRNA by double emulsion-solvent evaporation method using mPEG-b
      PNIPAM and a cationic lipid, 3beta [N-(N', N'-dimethylaminoethane)-carbamoyl]
      cholesterol [DC-Chol]. DENPs were observed by transmission electron microscopy
      and dynamical light scattering before and after 'cold shock' treatment. The
      encapsulation efficiency (EE) of siRNA in DENPs, which was measured by
      fluorescence spectrophotometer was 96.8% while it was significantly reduced to be
      23.2% when DC-Chol was absent. DENPs/siRNA NPs exhibited a thermo-sensitive siRNA
      release character that the cumulatively released amount of siRNA from cold shock
      was approximately 2.2 folds higher after 7 days. In vitro luciferase silencing
      experiments indicated that DENPs showed potent gene silencing efficacy in HeLa
      Luc cells (HeLa cells steadily expressed luciferase), which was further enhanced
      by a cold shock. Furthermore, MTT assay showed that cell viability with
      DENPs/siRNA up to 200 nM remained above 80%. We also observed that most of siRNA
      was accumulated in kidney mediated by DENPs instead of liver and spleen in vivo
      experiments. Thus, DENPs as a cold shock responsive quick release model for siRNA
      or hydrophilic macromolecules delivery provide a new way to nanocarrier design
      and clinic therapy. 

PMID- 25566876
TI  - An injured tissue affects the opposite intact peritoneum during postoperative
      adhesion formation.
AB  - The pathophysiology of adhesion formation needs to be clarified to reduce the
      adhesion-related morbidity. The epithelial characteristics of the peritoneum
      suggest a protective role against adhesion formation, yet how the peritoneum is
      involved in adhesion formation is not well characterized. We microscopically
      observed an experimental model of adhesion formation to investigate the effects
      of an injured tissue on the opposite intact peritoneum. Adhesions were induced
      between injured and intact hepatic lobes, and the intact peritoneum opposite to
      the injured tissue was examined for 8 days. The opposite intact peritoneum was
      denuded of mesothelial cells for 6 hours, and the remnant mesothelial cells
      changed morphologically for 24 hours. The detachment of mesothelial cells allowed
      fibrin to attach to the basement membrane of the opposite peritoneum, connecting
      the two lobes. Moreover, macrophages and myofibroblasts accumulated between the
      two lobes, and angiogenesis occurred from the opposite intact lobe to the injured
      lobe. These observations indicate that an injured tissue deprives the opposite
      intact peritoneum of its epithelial structure and causes fibrous adhesions to the
      opposite intact tissue. This study implies a possible role of mesothelial cells
      for barrier function against adhesion formation, that is, keeping mesothelial
      cells intact might lead to its prophylaxis.

PMID- 25566879
TI  - HIV risks and HIV prevention among female sex workers in two largest urban
      settings in Croatia, 2008-2014.
AB  - Harm reduction-based HIV prevention has been in place among female sex workers
      (FSWs) in Croatia for more than a decade. However, little is known about how well
      the existing programs meet the needs of FSWs in an environment where sex work
      remains criminalized and highly stigmatized. This study aims to assess changes in
      FSWs' vulnerability to HIV infection in the 2008-2014 period. Using convenience
      samples of FSWs in Croatia's two largest urban settings, behavioral data were
      collected in 2007-2008 and 2014. Outreach workers interviewed 154 FSWs in the
      first wave of the survey and 158 in the second. The period under observation was
      characterized by a stable prevalence of most HIV-relevant risk behaviors and
      experiences. Significant changes in client-based victimization and HIV knowledge
      were observed only among FSWs in the capital city. Substantial and mostly
      sustained levels of sexual and nonsexual victimization call for more research
      into the limits of the current behavior-based harm reduction approach to HIV
      prevention in the country. 

PMID- 25566878
TI  - Effect of nine diets on xenobiotic transporters in livers of mice.
AB  - 1. Lifestyle diseases are often caused by inappropriate nutrition habits and
      attempted to be treated by polypharmacotherapy. Therefore, it is important to
      determine whether differences in diet affect the disposition of drugs. Xenobiotic
      transporters in the liver are essential in drug disposition. 2. In the current
      study, mice were fed one of nine diets for 3 weeks. The mRNAs of 23 known
      xenobiotic transporters in livers of mice were quantified by microarray analysis,
      and validated by branched DNA assay. The mRNAs of 15 transporters were altered by
      at least one diet. Diet-restriction (10) and the atherogenic diet (10) altered
      the expression of the most number of transporters, followed by western diet (8),
      high-fat diet (4), lab chow (2), high-fructose diet (2) and EFA-deficient diet
      (2), whereas the low n-3 FA diet had no effect on these transporters. Seven of
      the 11 xenobiotic transporters in the Slc family, three of four in the Abcb
      family, two of four in the Abcc family and all three in the Abcg family were
      changed significantly. 3. This first comprehensive study indicates that
      xenobiotic transporters are altered by diet, and suggests there are likely diet
      drug interactions due to changes in the expression of drug transporters.

PMID- 25566880
TI  - Histotripsy of the Prostate in a Canine Model: Characterization of Post-Therapy
      Inflammation and Fibrosis.
AB  - INTRODUCTION: Histotripsy is a nonthermal, noninvasive, pulsed ultrasound
      technology that homogenizes tissue within the targeted volume. From previous
      experiments, it appeared that the resultant fibrotic response from histotripsy
      was limited compared with the typical tissue response seen after thermoablation.
      The objective of this study was to characterize the inflammatory response and
      quantify patterns of collagen deposition 6 weeks after in vivo canine prostate
      histotripsy. METHODS: Histotripsy was applied to the left half of eight canine
      prostates to produce an intraparenchymal zone of tissue homogenization. Six weeks
      after treatment, prostates were harvested, sectioned, and stained with
      hematoxylin and eosin for histologic evaluation, CD3, CD20, and Mac387
      immunohistochemistry to characterize the inflammatory components, and picrosirius
      red staining to identify collagen. RESULTS: Seven of eight treated prostates
      exhibited only minimal residual inflammation. Visual microscopic analysis of
      picrosirius red slides revealed a band of dense collagen (0.5 mm wide)
      immediately adjacent to the cavity produced by histotripsy. This was surrounded
      by a second band (1 mm wide) of less dense collagen interspersed among glandular
      architecture. A lobar distribution of epithelial atrophy and basal cell
      hyperplasia reminiscent of periurethral glands and ducts was apparent surrounding
      the margin of the treatment cavities. Tissue loss (-31%) was apparent on the
      treated side of all prostates while four demonstrated a net decrease in collagen
      content. CONCLUSIONS: In vivo histotripsy of canine prostate produced a decrease
      in prostate volume coupled with a limited inflammatory and fibrotic response. A
      narrow (1.5 mm) band of fibrosis around the empty, reepithelialized treatment
      cavity was observed 6 weeks after treatment. In four cases, an overall reduction
      in collagen content was measured. Further studies are planned to correlate these
      histologic findings with alteration in mechanical tissue properties and to
      explore histotripsy strategies for treatment of benign prostatic hyperplasia that
      optimize tissue volume removal with minimization of fibrosis.

PMID- 25566882
TI  - Cytoskeleton remodelling of confluent epithelial cells cultured on porous
      substrates.
AB  - The impact of substrate topography on the morphological and mechanical properties
      of confluent MDCK-II cells cultured on porous substrates was scrutinized by means
      of various imaging techniques as well as atomic force microscopy comprising force
      volume and microrheology measurements. Regardless of the pore size, ranging from
      450 to 5500 nm in diameter, cells were able to span the pores. They did not crawl
      into the holes or grow around the pores. Generally, we found that cells cultured
      on non-porous surfaces are stiffer, i.e. cortical tension rises from 0.1 to 0.3
      mN m(-1), and less fluid than cells grown over pores. The mechanical data are
      corroborated by electron microscopy imaging showing more cytoskeletal filaments
      on flat samples in comparison to porous ones. By contrast, cellular compliance
      increases with pore size and cells display a more fluid-like behaviour on larger
      pores. Interestingly, cells on pores larger than 3500 nm produce thick actin
      bundles that bridge the pores and thereby strengthen the contact zone of the
      cells. 

PMID- 25566881
TI  - Modelling epidermis homoeostasis and psoriasis pathogenesis.
AB  - We present a computational model to study the spatio-temporal dynamics of
      epidermis homoeostasis under normal and pathological conditions. The model
      consists of a population kinetics model of the central transition pathway of
      keratinocyte proliferation, differentiation and loss and an agent-based model
      that propagates cell movements and generates the stratified epidermis. The model
      recapitulates observed homoeostatic cell density distribution, the epidermal
      turnover time and the multilayered tissue structure. We extend the model to study
      the onset, recurrence and phototherapy-induced remission of psoriasis. The model
      considers psoriasis as a parallel homoeostasis of normal and psoriatic
      keratinocytes originated from a shared stem cell (SC) niche environment and
      predicts two homoeostatic modes of psoriasis: a disease mode and a quiescent
      mode. Interconversion between the two modes can be controlled by interactions
      between psoriatic SCs and the immune system and by normal and psoriatic SCs
      competing for growth niches. The prediction of a quiescent state potentially
      explains the efficacy of multi-episode UVB irradiation therapy and recurrence of
      psoriasis plaques, which can further guide designs of therapeutics that
      specifically target the immune system and/or the keratinocytes. 

PMID- 25566883
TI  - Timing and severity of immunizing diseases in rabbits is controlled by seasonal
      matching of host and pathogen dynamics.
AB  - Infectious diseases can exert a strong influence on the dynamics of host
      populations, but it remains unclear why such disease-mediated control only occurs
      under particular environmental conditions. We used 16 years of detailed field
      data on invasive European rabbits (Oryctolagus cuniculus) in Australia, linked to
      individual-based stochastic models and Bayesian approximations, to test whether
      (i) mortality associated with rabbit haemorrhagic disease (RHD) is driven
      primarily by seasonal matches/mismatches between demographic rates and
      epidemiological dynamics and (ii) delayed infection (arising from
      insusceptibility and maternal antibodies in juveniles) are important factors in
      determining disease severity and local population persistence of rabbits. We
      found that both the timing of reproduction and exposure to viruses drove
      recurrent seasonal epidemics of RHD. Protection conferred by insusceptibility and
      maternal antibodies controlled seasonal disease outbreaks by delaying infection;
      this could have also allowed escape from disease. The persistence of local
      populations was a stochastic outcome of recovery rates from both RHD and
      myxomatosis. If susceptibility to RHD is delayed, myxomatosis will have a
      pronounced effect on population extirpation when the two viruses coexist. This
      has important implications for wildlife management, because it is likely that
      such seasonal interplay and disease dynamics has a strong effect on long-term
      population viability for many species. 

PMID- 25566886
TI  - Synthesis of key macrolactone structure of resin glycosides using a Keck
      macrolactonization method.
AB  - We present in this paper the efficient synthesis of three macrocyclic lactone
      units which are core structures of natural resin glycosides by the use of a Keck
      macrolactonization approach. 

PMID- 25566884
TI  - Crystal growth of bullet-shaped magnetite in magnetotactic bacteria of the
      Nitrospirae phylum.
AB  - Magnetotactic bacteria (MTB) are known to produce single-domain magnetite or
      greigite crystals within intracellular membrane organelles and to navigate along
      the Earth's magnetic field lines. MTB have been suggested as being one of the
      most ancient biomineralizing metabolisms on the Earth and they represent a
      fundamental model of intracellular biomineralization. Moreover, the determination
      of their specific crystallographic signature (e.g. structure and morphology) is
      essential for palaeoenvironmental and ancient-life studies. Yet, the mechanisms
      of MTB biomineralization remain poorly understood, although this process has been
      extensively studied in several cultured MTB strains in the Proteobacteria phylum.
      Here, we show a comprehensive transmission electron microscopy (TEM) study of
      magnetic and structural properties down to atomic scales on bullet-shaped
      magnetites produced by the uncultured strain MYR-1 belonging to the Nitrospirae
      phylum, a deeply branching phylogenetic MTB group. We observed a multiple-step
      crystal growth of MYR-1 magnetite: initial isotropic growth forming cubo
      octahedral particles (less than approx. 40 nm), subsequent anisotropic growth and
      a systematic final elongation along [001] direction. During the crystal growth,
      one major {111} face is well developed and preserved at the larger basal end of
      the crystal. The basal {111} face appears to be terminated by a tetrahedral
      octahedral-mixed iron surface, suggesting dimensional advantages for binding
      protein(s), which may template the crystallization of magnetite. This study
      offers new insights for understanding magnetite biomineralization within the
      Nitrospirae phylum. 

PMID- 25566888
TI  - Hello, limitations! The paradoxical power of limits in scientific writing.

PMID- 25566889
TI  - Current status of genodermatoses: an Indian perspective.

PMID- 25566890
TI  - Phototherapy for atopic dermatitis.
AB  - BACKGROUND: The aim of these guidelines is to review the available published
      literature regarding the effectiveness of phototherapy and photochemotherapy in
      atopic dermatitis and put forward recommendations regarding their use in atopic
      dermatitis. MATERIALS AND METHODS: A literature search was performed to collect
      data from PubMed, EMBASE, and the Cochrane Library published till March 2014.
      Keywords used were "phototherapy", "photochemotherapy", "NB-UVB", "BBUVB",
      "PUVA", "UVA1", "atopic dermatitis", and "atopic eczema". Systematic reviews,
      meta-analysis, national guidelines, randomized controlled trials, prospective
      open label studies, and retrospective case series in English literature
      mentioning use of above-mentioned keywords were reviewed. RESULTS: Six hundred
      and eighty eight studies were evaluated, 38 of which fulfilled the criteria for
      inclusion in the guidelines. CONCLUSIONS AND RECOMMENDATIONS: Both UV1 and narrow
      band UVB are effective in significantly decreasing the eczema severity although
      UV1 may be preferred in acute flares and narrow-band UVB in chronic eczema,
      especially in adults (Level of evidence 1+, Grade of recommendation A). Among
      various doses of UVA1, medium dose UVA1 may be preferred over others as its
      efficacy is similar to high dose and better than low dose UVA1 phototherapy.
      Narrow-band UVB is preferred to broad-band UVB (Level of evidence 1+, Grade of
      recommendation A). Medium-dose UVA1 is similar in efficacy to narrow-band UVB
      (Level of evidence 1+, Grade of recommendation A). In children, despite its
      efficacy, narrow-band UVB phototherapy should be used only as a second line
      therapy due to its potential for long-term adverse effects (Level of evidence 2+,
      Grade of recommendation B).

PMID- 25566891
TI  - Clinical profile and mutation analysis of xeroderma pigmentosum in Indian
      patients.
AB  - BACKGROUND: Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder
      characterized by cutaneous and ocular photosensitivity and an increased risk of
      developing cutaneous neoplasms. Progressive neurological abnormalities develop in
      a quarter of XP patients. AIM: To study the clinical profile and perform a
      mutation analysis in Indian patients with xeroderma pigmentosum. METHODS: Ten
      families with 13 patients with XP were referred to our clinic over 2 years. The
      genes XPA, XPB and XPC were sequentially analyzed till a pathogenic mutation was
      identified. RESULTS: Homozygous mutations in the XPA gene were seen in patients
      with moderate to severe mental retardation (6/10 families) but not in those
      without neurological features. Two unrelated families with a common family name
      and belonging to the same community from Maharashtra were found to have an
      identical mutation in the XPA gene, namely c.335_338delTTATinsCATAAGAAA
      (p.F112SfsX2). Testing of the XPC gene in two families with four affected
      children led to the identification of the novel mutations c.1243C>T or p.R415X
      and c.1677C>A or p.Y559X. In two families, mutations could not be identified in
      XPA, XPB and XPC genes. LIMITATION: The sample size is small. CONCLUSION: Indian
      patients who have neurological abnormalities associated with XP should be
      screened for mutations in the XPA gene.

PMID- 25566892
TI  - Analysis of twenty pediatric cases of tuberous sclerosis complex: are we doing
      enough?
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is a neuro-cutaneous disease
      characterized by hamartoma formation in various organs particularly the skin,
      brain, eye, kidney, heart and lungs. Patients usually have multisystem
      involvement and thus present to different medical specialties with varied
      complaints while the true nature of the disease and the hidden manifestations may
      remain unattended. AIM: To assess the frequency and characteristics of various
      cutaneous and systemic manifestations in TSC and the total impact on different
      system in a cohort of pediatric patients. METHODS: The study included 20 patients
      fulfilling the diagnostic criteria for TSC from dermatology, pediatrics, and
      neurology department. Detailed history, examination, and investigations such as
      chest X-ray, electrocardiography (ECG), ultrasonography (USG) abdomen,
      echocardiography, fundoscopy, computed tomography (CT) scan of brain and abdomen
      were done. RESULTS: Dermatological manifestations included ash leaf macules,
      angiofibromas, shagreen patch, and fibrous plaque. Systemic findings observed
      were subependymal calcified nodules, subependymal giant cell astrocytoma,
      cortical tubers, renal cysts, angiomyolipomas, lung cyst, retinal hamartomas,
      mental deficits and epilepsy. LIMITATION: Wechsler's Intelligence Scale for
      Children would have been more appropriate for assessing the intelligence. Dental
      check-up was not done in our group of patients. CONCLUSION: Our study highlights
      the wide variety of cutaneous and systemic manifestations of TSC. The study
      emphasizes the need for comprehensive multidisciplinary treatment and periodic
      follow-up which are necessary for appropriate management of this multisystem
      disorder. Counseling regarding education and rehabilitation of the patients and
      genetic counseling of parents are important.

PMID- 25566893
TI  - Histopathological characteristics of post kala-azar dermal leishmaniasis: a
      series of 88 patients.
AB  - BACKGROUND: Post kala azar dermal leishmaniasis (PKDL) is a sequel to visceral
      leishmaniasis or kala azar seen predominantly in the Indian subcontinent and
      Africa. Histopathological descriptions of the condition are limited. METHODS:
      Biopsies of 88 skin and 16 mucosal lesions were evaluated for histopathological
      findings on formalin-fixed, paraffin-embedded tissues. RESULTS: There were 71
      (80.7%) males and 17 (19.3%) females with a mean age of 24.8 and 28.5 years,
      respectively. A past history of kala azar was present in 64 (72.7%) patients and
      post kala azar dermal leishmaniasis developed a mean of 6.2 years after visceral
      leishmaniasis. Of the biopsies studied, the clinical lesions were macular in 14
      (15.9%), papulo-nodular in 32 (36.3%) and showed both macules and papulo-nodules
      in 42 (47.8%). Follicular plugging was a common epidermal finding. A clear Grenz
      zone was frequently noted. The dermal infiltrates were arranged mainly in three
      patterns: superficial perivascular infiltrates in 16 (18.1%), perivascular and
      perifollicular infiltrates in 24 (27.3%) and diffuse infiltrates in 41 (46.6%)
      biopsies. Leishman-Donovan (LD) bodies were noted in 13 (44.9%) of 69 cases on
      slit-skin smear and in 25 (28.4%) of 88 biopsies. In 16 patients, where both skin
      and mucosal biopsies were available, LD bodies were identified in 10 (62.5%)
      mucosal biopsies as compared to 3 (18.7%) skin biopsies. LIMITATIONS: The
      retrospective nature of the study and the lack of controls were limitations.
      CONCLUSION: The various histomorphological patterns of post kala azar dermal
      leishmaniasis are a useful clue to the diagnosis even when LD bodies have not
      been detected. This study also suggests that LD bodies are more frequently seen
      in mucosal biopsies in comparison to cutaneous biopsies.

PMID- 25566894
TI  - Monthly rifampicin, ofloxacin, and minocycline therapy for generalized and
      localized granuloma annulare.
AB  - BACKGROUND: The localized form of granuloma annulare is usually self-limiting,
      resolving within 2 years. Generalized granuloma annulare, on the other hand, runs
      a protracted course, with spontaneous resolution being rare. It is also
      characterized by a later age of onset, an increased incidence of diabetes
      mellitus, poor response to therapy, and an increased prevalence of HLA Bw35.
      OBJECTIVE: To assess the efficacy of monthly pulsed rifampicin, ofloxacin, and
      minocycline (ROM) therapy in the management of granuloma annulare. METHODS: Six
      biopsy proven patients of granuloma annulare were included in the study, five of
      the generalized variety, and one localized. Three of these patients were
      resistant to standard modalities of treatment. All six patients were treated with
      pulses of once monthly ROM till complete resolution of all lesions. Results were
      analyzed in terms of complete resolution of lesions and side effects. Presence of
      comorbid conditions was noted. RESULT: All six patients were successfully treated
      with 4-8 pulses of monthly ROM. None of the patients reported any adverse
      effects. LIMITATIONS: Small sample size and the lack of a control group are
      limitations. CONCLUSION: Treatment with pulses of once monthly ROM caused
      complete resolution of lesions in both localized and generalized granuloma
      annulare, even in cases recalcitrant to conventional therapy. There were no side
      effects in any of the patients. Larger trials are needed to substantiate the
      efficacy of monthly ROM in granuloma annulare.

PMID- 25566895
TI  - Epidermolysis bullosa pruriginosa: a case with a novel mutation and co-existent
      lichen amyloidosus.
AB  - Epidermolysis bullosa pruriginosa is a rare variant of dystrophic epidermolysis
      bullosa characterized by severely pruritic and cicatricial lesions localized to
      the extensor extremities. We report a Singaporean Chinese male with epidermolysis
      bullosa pruriginosa with an underlying novel mutation in the COL7A1 gene. A
      heterozygous acceptor splice site mutation IVS67-1G>T probably led to in-frame
      skipping of exon 68 (36-basepairs), resulting in a loss of 12 amino acids. Among
      his three children, only the youngest son, who had bilateral big toenail
      thickening, possessed the same mutation. His skin biopsy one decade ago revealed
      association of focal amyloidosis; a recent skin biopsy showed more established
      features of lichen amyloidosis. It is debatable whether the cutaneous amyloidosis
      was a secondary or primary phenomenon. Our report highlights that the diagnosis
      of epidermolysis bullosa pruriginosa may be obscured when cutaneous amyloidosis
      is coexistent. 

PMID- 25566896
TI  - Drug eruptions induced by allopurinol associated with HLA-B*5801.
AB  - Allopurinol, a drug commonly used for treating gout and hyperuricemia, is a
      frequent cause of drug eruptions. Recent investigations suggest that HLA
      BFNx015801 allele is a very strong marker for allopurinol-induced cutaneous
      adverse drug reactions (cADRs). In this article we report two cases of
      allopurinol-induced drug eruptions in patients carrying the HLA-BFNx015801 allele
      and review the literature on the association between HLA-BFNx015801 and
      allopurinol-induced cADRs based on a MEDLINE and PubMed search. 

PMID- 25566897
TI  - Familial angiokeratoma corporis diffusum without identified enzyme defect.
AB  - Angiokeratoma corporis diffusum is the cutaneous hallmark of several rare
      inherited lysosomal diseases associated with specific enzyme deficiencies in the
      metabolism of glycoproteins, most notably Fabry disease. These defects result in
      many systemic manifestations. Here, we report a rare familial case of
      angiokeratoma corporis diffusum that developed at puberty with no major systemic
      manifestations and no underlying enzyme defect or gene mutation. Familial
      angiokeratoma corporis diffusum without identified enzyme defect appears to be a
      distinct clinical entity with a benign course. 

PMID- 25566898
TI  - Aggressive calciphylaxis in end-stage renal disease after a failed kidney
      allograft.

PMID- 25566899
TI  - Interferons.

PMID- 25566900
TI  - The efficacy of macrolides and acyclovir in pityriasis rosea.

PMID- 25566901
TI  - Author's Response--The efficacy of azithromycin in pityriasis rosea: a
      randomized, double-blind, placebo-controlled trial.

PMID- 25566902
TI  - Cutaneous mercury granuloma following accidental occupational exposure.

PMID- 25566904
TI  - Elastosis linearis rubra nasi: a new clinical entity in the spectrum of localized
      nodular elastosis.

PMID- 25566903
TI  - Subcutaneous human dirofilariasis.

PMID- 25566905
TI  - Reactive eccrine syringofibroadenoma on a leprous foot.

PMID- 25566906
TI  - Hyperpigmentation along Blaschko lines.

PMID- 25566907
TI  - Erosive adenomatosis of the nipple in a man.

PMID- 25566908
TI  - Acrodermatitis enteropathica in an infant with normal zinc levels.

PMID- 25566909
TI  - Blaschkoid mastocytosis.

PMID- 25566910
TI  - Enalapril induced normocomplementemic urticarial vasculitis.

PMID- 25566911
TI  - Congenital self-healing Langerhans cell histiocytosis in a male neonate.

PMID- 25566912
TI  - Pilomatricoma with a bullous appearance.

PMID- 25566913
TI  - Giant eccrine spiradenoma mimicking a malignant tumor.

PMID- 25566914
TI  - Allergic contact dermatitis due to clotrimazole with cross-reaction to
      miconazole.

PMID- 25566915
TI  - Allergic contact dermatitis to Parthenium hysterophorus mimicking actinic
      prurigo.

PMID- 25566916
TI  - Does contact allergy to benzocaine cause orodynia?

PMID- 25566917
TI  - Fox-Fordyce disease: a report of 2 cases responding to topical clindamycin.

PMID- 25566918
TI  - Hailey-Hailey disease with skin lesions at unusual sites and a good response to
      acitretin.

PMID- 25566919
TI  - Lack of effectiveness of keratin dressings in epidermolysis bullosa.

PMID- 25566920
TI  - A nose for trouble. Diagnosis: Granuloma faciale.

PMID- 25566921
TI  - Intravenous methylprednisolone pulse therapy in severe alopecia areata.
AB  - BACKGROUND: Severe, extensive, therapy resistant alopecia areata represents a
      clinical challenge. Systemic corticosteroids are a therapeutic tool that still
      needs to be evaluated. AIM: The purpose of this study was to assess the efficacy
      and safety of methylprednisolone pulse therapy in alopecia areata and to find
      prognostic factors for a favourable outcome. METHODS: A total of 32 patients with
      severe multifocal alopecia areata (more than 40% scalp hair loss), alopecia
      totalis, and alopecia universalis were treated with infusions of 500 mg
      methylprednisolone for 3 days every month for 3 consecutive months. The end point
      of the study was 12 months. RESULTS: Of 32 patients, 26 (81.3%) reported a
      clinical response. Four patients (12.5%) showed complete hair regrowth, 6
      patients (18.8%) showed >50% hair regrowth, ten (31.3%) had <50% hair regrowth, 6
      (18.75%) were non responders, and another 6 patients (18.8%) had relapse after an
      initial regrowth. Multivariate analysis revealed that patients reporting at the
      first episode and those with multifocal disease had the best results. CONCLUSION:
      Methylprednisolone infusions represent a possible therapeutic option for patients
      with multifocal alopecia areata and those presenting with the first episode of
      the disease.

PMID- 25566922
TI  - Giant facial cutaneous tuberculosis.

PMID- 25566923
TI  - Insect bite reaction and HIV infection.

PMID- 25566924
TI  - Acute generalized exanthematous pustulosis in a child probably induced by
      terbinafine.

PMID- 25566925
TI  - Recurrent Spitz nevus with multiple satellite lesions on perineum.

PMID- 25566926
TI  - Secondary comedones after waxing.

PMID- 25566927
TI  - Viva questions from the IJDVL.

PMID- 25566929
TI  - In memory of William H. Glaze (November 21, 1934-December 17, 2014).

PMID- 25566928
TI  - Investigating critical effects of variegated lubricants, glidants and hydrophilic
      additives on lag time of press coated ethylcellulose tablets.
AB  - The research envisaged focuses on vital impacts of variegated lubricants,
      glidants and hydrophilic additives on lag time of press coated ethylcellulose
      (EC) tablets using prednisone as a model drug. Several lubricants and glidants
      such as magnesium stearate, colloidal SiO2, sodium stearyl fumarate, talc,
      stearic acid, polyethylene glycol (6000) and glyceryl behenate were investigated
      to understand their effects on lag time by changing their concentrations in outer
      coat. Further, the effects of hydrophilic additives on lag time were examined for
      hydroxypropylmethylcellulose (E5), hydroxypropylcellulose (EF and SSL), povidone
      (K30), copovidone, polyethylene glycol (4000), lactose and mannitol. In vitro
      drug release testing revealed that each selected lubricant/glidant, if present
      even at concentration of 0.25% w/w, significantly reduced the lag time of press
      coated tablets. Specifically, colloidal SiO2 and/or magnesium stearate were
      detrimental while other lubricants/glidants were relatively less injurious. Among
      hydrophilic additives, freely water soluble fillers had utmost influence in lag
      time, whereas, comparatively less impact was observed with polymeric binders.
      Concisely, glidant and lubricant should be chosen to have minimal impact on lag
      time and further judicious selection of hydrophilic additives should be exercised
      for modulating lag time of pulsatile release formulations. 

PMID- 25566930
TI  - Pharmacokinetics, safety, and tolerability of edoxaban in end-stage renal disease
      subjects undergoing haemodialysis.
AB  - Edoxaban is an oral, direct, once-daily, factor Xa inhibitor developed for stroke
      prevention in patients with atrial fibrillation and for the treatment and
      secondary prevention of recurrent thromboembolism in patients with acute
      symptomatic venous thromboembolism. Among elderly patients who require
      anticoagulation therapies, some may have end-stage renal disease (ESRD). This
      open-label, phase 1, randomised, two-way crossover study was conducted to
      evaluate the pharmacokinetics of edoxaban in 10 subjects on haemodialysis.
      Eligible subjects with ESRD on chronic haemodialysis received a single, oral dose
      of edoxaban 15 mg 2 hours (h) prior to (on-dialysis) or in between (off-dialysis)
      haemodialysis sessions. Haemodialysis resulted in a minor decrease in mean total
      exposure (AUC0-infinity; 676.2 ng.h/ml) as compared with that observed in
      subjects off-dialysis (691.7 ng.h/ml). Mean maximum observed plasma concentration
      (Cmax) values were comparable between on-dialysis and off-dialysis treatments
      (53.3 vs 56.3 ng/ml, respectively). Mean apparent total body clearance (CL/F)
      values were 24.1 and 22.5 l/h during the on-dialysis and off-dialysis treatment
      periods, respectively. Dialyser clearance was 5.7 l/h and haemodialysis clearance
      was 6.1 l/h. Haemodialysis clearance was only 6.1 l/h, suggesting that it only
      accounts for one-fourth of the total clearance in these subjects. A single, oral
      dose of 15 mg of edoxaban was well tolerated by subjects with ESRD. In
      conclusion, based on these single-dose PK data, a supplementary dose of edoxaban
      may not be required following a haemodialysis session. Importantly, haemodialysis
      is not an effective mechanism for removal of edoxaban from the blood. 

PMID- 25566931
TI  - Sudden flaccid paralysis.
AB  - Periodic thyrotoxic paralysis is a genetic condition, rare in the West and in
      Caucasians. Thyrotoxicosis, especially in western hospitals, is an easily
      overlooked cause of sudden-onset paralysis. We present a case of a 40-year-old
      man who awoke one morning unable to stand. He had bilateral lower limb flaccid
      weakness of 0/5 with reduced reflexes and equivocal plantars; upper limbs were
      3/5 with reduced tone and reflexes. ECG sinus rhythm was at a rate of 88/min. PR
      interval was decreased and QT interval increased. Bloods showed potassium of 1.8
      mEq/L (normal range 3.5-5), free T4 of 29.2 pmol/L (normal range 6.5-17) and
      thyroid-stimulating hormone (TSH) of <0.01 mIU/L (normal range 0.35-4.94). Random
      urinary potassium was 8.8 mEq/L (normal range 12.5-62.5). The patient was
      admitted initially to intensive therapy unit and given intravenous potassium. His
      symptoms resolved within 24 h. He was diagnosed with thyrotoxic periodic
      paralysis. He was discharged on carbimazole and propanolol, and follow-up was
      arranged in the endocrinology clinic. 

PMID- 25566932
TI  - Epidural abscess and feculent meningitis secondary to stercoral ulcer rupture.

PMID- 25566933
TI  - Bilateral thalamic bleed and cerebral venous sinus thrombosis in Japanese
      encephalitis.
AB  - Japanese encephalitis (JE) is a potentially serious form of viral encephalitis
      with varied clinicoradiological manifestations. We report the case of a 19-year
      old girl admitted with headache, vomiting and altered sensorium in the absence of
      fever, whose cerebrospinal fluid analysis showed lymphocytic pleocytosis with
      significant protein content and positive serum IgM JE antibodies. MRI with
      venography revealed bilateral thalamic haemorrhage and cerebral venous sinus
      thrombosis. Although thalamic hypodensities are a well-described feature,
      thalamic haemorrhage and cerebral venous thrombosis are distinctly rare in JE.
      This report highlights the role of imaging in cases of encephalitis in general
      and JE in particular, in the early detection of uncommon manifestations that may
      complicate these diseases. 

PMID- 25566934
TI  - Ischaemic necrosis of the tongue.
AB  - Necrosis of the tongue is a rare clinical finding. The rich vascularity of the
      tongue means necrosis is uncommon but it has been reported secondary to giant
      cell arthritis, radiotherapy and ischaemia. We report the case of a 61-year-old
      man admitted with an acute abdomen, who later developed gross swelling of the
      tongue, secondary to ischaemic necrosis, which necessitated tracheostomy
      placement. The ischaemia was managed conservatively with heparinisation and by
      allowing the ischaemic area to demarcate and slough off naturally. 

PMID- 25566935
TI  - Nasoalveolar cyst: an enigma for the dentist.
AB  - A nasoalveolar cyst is a rare, non-odontogenic soft tissue cyst encountered in
      the anterior maxillary labial sulcus as an asymptomatic soft tissue swelling.
      Often, patients with these cysts report them to the dental clinic where they are
      mistaken for odontogenic lesions by the dental surgeon, especially if concomitant
      dental problems are present. They cannot be detected by routine conventional
      dental radiography as they are peripheral, lying within the mucosa thereby posing
      a diagnostic challenge. We document a case of a 47-year-old woman with a
      nasoalveolar cyst. 

PMID- 25566936
TI  - Optical coherence tomography surveillance following drug-eluting stent
      implantation.
AB  - Drug-eluting stents are currently used in the majority of percutaneous coronary
      interventions. Preclinical investigations and human autopsy studies have shown
      that the high efficacy of drug-eluting stents (DES) in preventing restenosis is
      achieved at the expense of a delay in healing. Optical coherence tomography (OCT)
      represents a novel intracoronary imaging tool to evaluate vascular healing
      response after stent implantation. Owing to its outstanding resolution in the
      catheter near-field, quantitative morphometric measures were complemented by more
      qualitative description of neointimal tissue characterization. Clinical imaging
      studies employing these methodologies gained valuable insights into vascular
      healing responses after DES implantation and are reported in this review.
      However, an important limitation of OCT imaging analysis, despite its high
      resolution, remains the inability to assess the precise cellular composition and
      functional capability of the neointimal tissue, especially of the endothelium.
      Future long-term clinical studies are warranted to determine the clinical
      relevance of surrogate parameters derived from preliminary OCT surveillance
      studies. 

PMID- 25566938
TI  - Long term CPAP effects in myocardial performance in OSA. Always predictable and
      measurable cardiac index?

PMID- 25566937
TI  - A genetic study on C5-TRAF1 and progression of joint damage in rheumatoid
      arthritis.
AB  - INTRODUCTION: The severity of joint damage progression in rheumatoid arthritis
      (RA) is heritable. Several genetic variants have been identified, but together
      explain only part of the total genetic effect. Variants in Interleukin-6 (IL-6),
      Interleukin-10 (IL-10), C5-TRAF1, and Fc-receptor-like-3 (FCRL3) have been
      described to associate with radiographic progression, but results of different
      studies were incongruent. We aimed to clarify associations of these variants with
      radiographic progression by evaluating six independent cohorts. METHODS: In total
      5,895 sets of radiographs of 2,493 RA-patients included in six different
      independent datasets from the Netherlands, Sweden, Spain and North-America were
      studied in relation to rs1800795 (IL-6), rs1800896 (IL-10), rs2900180 (C5-TRAF1)
      and rs7528684 (FCRL3). Associations were tested in the total RA-populations and
      in anti-citrullinated peptide antibodies (ACPA)-positive and ACPA-negative
      subgroups per cohort, followed by meta-analyses. Furthermore, the associated
      region C5-TRAF1 was fine-mapped in the ACPA-negative Dutch RA-patients. RESULTS:
      No associations were found for rs1800795 (IL-6), rs1800896 (IL-10) and rs7528684
      (FCRL3) in the total RA-population and after stratification for ACPA. Rs2900180
      in C5-TRAF1 was associated with radiographic progression in the ACPA-negative
      population (P-value meta-analysis = 5.85 * 10(-7)); the minor allele was
      associated with more radiographic progression. Fine-mapping revealed a region of
      66Kb that was associated; the lowest P-value was for rs7021880 in TRAF1. The P
      value for rs7021880 in meta-analysis was 6.35 * 10(-8). Previous studies indicate
      that the region of rs7021880 was associated with RNA expression of TRAF1 and C5.
      CONCLUSION: Variants in IL-6, IL-10 and FCRL3 were not associated with
      radiographic progression. Rs2900180 in C5-TRAF1 and linked variants in a 66Kb
      region were associated with radiographic progression in ACPA-negative RA.

PMID- 25566939
TI  - Excessive fragmentary myoclonus in patients with Parkinson's disease: prevalence
      and clinico-polysomnographic profile.
AB  - OBJECTIVE AND BACKGROUND: Excessive fragmentary myoclonus (EFM) is characterized
      by subtle arrhythmic and excessive jerks that are usually asymmetric and
      asynchronous. EFM occurs in different areas of the body, mainly the face and
      distal parts of the arms and legs, and is detected by surface electromyography
      during sleep. The present study aimed to determine the prevalence of EFM in
      Parkinson's disease (PD) patients at a tertiary level outpatient clinic as well
      as to describe the clinical and polysomnographic profiles of these patients.
      METHODS: A total of 62 consecutive PD patients were included in the study.
      Patients were evaluated using the Brazilian version of the PD Sleep Scale,
      Portuguese Language version of Epworth's Daytime Sleepiness Scale validated for
      Brazilian population, Brazilian Portuguese version of PD Quality of Life Scale,
      and Global Deterioration Scale. Evaluation of the sleep disorders was performed
      by clinical interview and polysomnography. RESULTS: EFM was found in 62.7% of PD
      patients. EFM was found to be associated with obstructive sleep apnea syndrome
      and advanced age. CONCLUSIONS: EFM occurs in a significantly high proportion of
      PD patients and is related to obstructive sleep apnea syndrome (OSAS) and
      advanced age, so EFM should be systematically investigated by polysomnography
      (PSG) in PD patients.

PMID- 25566940
TI  - Central sleep apnea in pregnant women with sleep disordered breathing.
AB  - PURPOSE: Physiologic changes in the cardiac, respiratory, and renal systems in
      pregnancy likely impact ventilatory control. Though obstructive sleep apnea and
      snoring are common in the pregnant population, the predisposition to central
      respiratory events during sleep and the prevalence of such events is less well
      studied. The aim of this study was to assess the presence of central apneas
      during sleep in pregnant women and non-pregnant controls suspected of sleep
      disordered breathing. METHODS: Twenty-five pregnant women referred for
      polysomnography for sleep disordered breathing were compared with non-pregnant
      controls matched for age, body mass index, gender, and apnea hypopnea index
      (AHI). Central apnea index was defined as the number of central apneas per hour
      of sleep, and mixed apnea index was defined as the number of mixed apneas per
      hour of sleep. RESULTS: Sixty-four percent of pregnant women had a respiratory
      disturbance index >5 events per hour of sleep. Mean body mass index was 44.1 +/-
      6.9 kg/m(2) pregnant compared to 44.0 +/- 7.3 kg/m(2) in controls. The total
      number of central apneas observed during sleep in the pregnant group consisted of
      two central apneas in one patient, and of 98 central apneas in 11 patients in the
      control group (p = 0.05). Median central apnea index was low in both groups
      (pregnant 0, interquartile range (IQR) 0, 0 vs. non-pregnant 0, IQR 0, 0.2, p =
      0.04). Mixed apnea index was similarly low in both groups. CONCLUSION: Despite
      some physiologic changes of pregnancy that impact ventilatory control, the
      prevalence of central sleep apnea was low in our sample of overweight pregnant
      women with sleep-disordered breathing.

PMID- 25566941
TI  - Serum advanced glycation end products are associated with insulin resistance in
      male nondiabetic patients with obstructive sleep apnea.
AB  - PURPOSE: Advanced glycation end products (AGEs) play an important role in the
      pathogenesis of diabetic vascular complications. Recently, growing evidence has
      shown that AGEs could be involved in the pathogenesis of insulin resistance. It
      has also been suggested that circulating AGE are associated with insulin
      resistance in nondiabetic patients. This study investigated whether serum AGEs
      levels are associated with insulin resistance in nondiabetic patients with
      obstructive sleep apnea (OSA). METHODS: A total of 139 male nondiabetic patients
      with OSA were recruited for participation in the study. Serum AGE levels were
      examined using an enzyme-linked immunosorbent assay. Insulin resistance was
      determined using the homeostasis model assessment index (HOMA-IR). RESULTS: There
      was a significant correlation between serum AGEs and the apnea-hypopnea index
      (AHI) (r = 0.281, p = 0.014), duration of SaO2 < 90% (r = 0.267, p = 0.018),
      minimum SaO2 (r = -0.188, p = 0.046), high-sensitivity C-reactive protein (hsCRP)
      (r = 0.274, p = 0.012), and HOMA-IR (r = 0.303, p < 0.001). Multiple regression
      analysis showed that serum AGEs (p = 0.011), AHI (p = 0.024), waist circumference
      (p = 0.040), and hsCRP (p = 0.046) were independently associated with HOMA-IR
      (R(2) = 0.392). In addition, the strength of the correlation between serum AGEs
      and HOMA-IR was related to the severity of OSA. CONCLUSIONS: The present study
      indicated that serum AGE levels were associated with insulin resistance in male
      nondiabetic patients with OSA. These findings suggest that AGEs may play a role
      in insulin resistance in OSA and may also be a biomarker for patients with OSA
      with high risk of developing type 2 diabetes.

PMID- 25566942
TI  - Presence and severity of obstructive sleep apnea and remote outcomes of atrial
      fibrillation ablations - a long-term prospective, cross-sectional cohort study.
AB  - BACKGROUND: Prior studies suggested that obstructive sleep apnea (OSA) promotes
      recurrence of arrhythmia in patients after atrial fibrillation (AF) ablation.
      METHODS: In this prospective, long-term, observational study, we enrolled 290
      consecutive patients admitted for AF ablation. Prior to the ablation, all
      patients underwent a polygraphy sleep study for the diagnosis of OSA. After the
      procedure, patients were followed up for mean time of 30 months for AF
      reoccurrence. OSA was diagnosed when apnea-hypopnea index (AHI) was >=5. Patients
      were subsequently divided into groups according to the OSA severity: mild OSA
      (AHI 5-15/h), moderate OSA (AHI >15 and <=30/h), and severe (AHI >30/h). RESULTS:
      After excluding patients disqualified from the procedure, and those with central
      sleep apnea, the study population consisted of 251 patients, mean age 57.6 years
      [163 (64.9%) male]. OSA was present in 115 (45.8%) patients, while in 137 (54.6%)
      cases, we observed reoccurrence of AF. Recurrence was more often in patients
      with, than without, OSA (65.2 vs. 45.6%; p = 0.003). We also observed that along
      with rising OSA severity rose also the number of patients in whom AF was detected
      during the follow-up period (45.6 vs. 66.2 vs. 57.6 vs. 81.8%; p = 0.005; for non
      OSA, mild, moderate, and severe, respectively). CONCLUSIONS: OSA is highly
      prevalent in AF patients. The presence of OSA lowers chances on successful AF
      ablation. Early screening, and treatment for OSA in AF patients, may improve low
      success rates of AF ablation procedures.

PMID- 25566943
TI  - The sleep characteristics in symptomatic patients with Duchenne muscular
      dystrophy.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) causes serious health consequences
      that include impairment of the respiratory system and sleep. The aim of our study
      is to investigate the sleep architecture and respiratory profile during sleep of
      symptomatic patients with DMD without ventilatory support. METHODS: We evaluated
      polysomnography (PSG) of boys with DMD (n = 44) and a control group (n = 79) with
      sleep complaints that was matched in age but without neuromuscular disease.
      RESULTS: DMD patients presented sleep impairments when compared with the control
      group in terms of decreased sleep efficiency (72.4 +/- 1.9 vs 80.3 +/- 1.4 %, P =
      0.002) and increased apnea-hypopnea index (AHI) during nonrapid eye movement
      (NREM) sleep (1.6 +/- 0.3 vs 0.3 +/- 0.2/h, P = 0.003). The main changes were
      observed during rapid eye movement (REM) sleep: an increase in REM sleep latency
      (202.2 +/- 11.8 vs 152.3 +/- 8.6 min, P < 0.001), a reduced percentage of REM
      sleep (13.1 +/- 0.9 vs 17.9 +/- 0.7 %, P = 0.001), and exacerbation of AHI (8.7
      +/- 1.5 vs 1.0 +/- 1.1 events/h, P = 0.001). There was an increase in the total
      number of apneas, especially obstructive apneas (6.8 +/- 1.9 vs 0.8 +/- 1.3, P =
      0.013). CONCLUSIONS: The sleep and respiratory profile during sleep of patients
      with DMD are compromised. The results suggest that these changes reflect the
      muscle weakness inherent in DMD and are demonstrated mainly during REM sleep.
      Thus, the use of PSG is important to identify sleep-disordered breathing at an
      early stage, before deciding when to introduce noninvasive respiratory support
      for prevention of respiratory complications.

PMID- 25566944
TI  - Obstructive sleep apnea among hospitalized patients in Spain, analysis of
      hospital discharge data 2008-2012.
AB  - BACKGROUND: The aim of this study is to describe clinical characteristics,
      diagnostic and therapeutic procedure (polysomnography and continuous positive
      airway pressure (CPAP)/bi-level positive airway pressure (BPAP)), comorbidity,
      length of hospital stay (LOHS), discharge destination, and in-hospital mortality
      (IHM) of patients hospitalized for obstructive sleep apnea (OSA) in Spain over a
      5-year study period. METHODS: We included all patients who were hospitalized for
      OSA (ICD9-CM code 327.23) as primary or secondary diagnosis between 2008 and
      2012. Data were collected from the National Hospital Discharge Database, covering
      the entire Spanish population. RESULTS: We identified 196,769 discharges of
      patients admitted for OSA. The number of patients with OSA as primary or
      secondary diagnosis increased from 2008 to 2012 from 5358 to 7992 and 14,916 to
      51,135 respectively. The mean age was 50.7 +/- 20.3 years in patients admitted
      for OSA as primary diagnosis (n = 32,010) and 63.7 +/- 17.6 years in patients
      admitted for OSA as secondary diagnosis (n = 164,759). The most common secondary
      diagnoses for patients discharged with a primary diagnosis of OSA was arterial
      hypertension (19.0%), obesity (16.9%), disorders of lipid metabolism (8.01%) and
      diabetes mellitus (6.48%). The most common primary diagnoses for patients
      discharged with a secondary diagnosis of OSA were obesity (12.5%), heart failure
      (9.6%), and chronic bronchitis (4.5%). The percentage of patients that received
      continuous positive airway pressure (CPAP)/bi-level positive airway pressure
      (BPAP) therapy was 11.3%. Patients who received this therapy had a higher length
      of stay compared with those who did not (10.4 +/- 14.1 versus 7.3 +/- 9.5 days,
      respectively, p < 0.05) and were less likely to be discharged to home (87.2
      versus 91.1%, p < 0.05). The mortality was higher in the first group of patients
      (9 versus 5.6%, p < 0.05). Multivariate analysis showed that each year from 2008
      to 2012, the mean probability of having OSA as primary diagnosis increased an
      average of 8%, and 33% as secondary diagnosis, after adjusting for other
      variables. CONCLUSIONS: The results of this study reveal a national perspective
      on the characteristics and management of OSA in hospitalized patients in Spain
      during the period of 2008-2012. The burden of the disease seems to be increasing
      in Spain. Clinical studies are needed to provide a better knowledge of OSA in
      this subgroup of patients.

PMID- 25566946
TI  - RKKY interaction in graphene with a line defect.
AB  - A kind of extended line defect is currently an experimentally available one
      dimensional topological structure in graphene lattice. It modifies the electronic
      properties of graphene in many aspects. For example, it induces an even-parity
      boundary state which has linear dispersion and breaks the electron-hole symmetry
      of the graphene electronic structure. In addition, the line defect possesses much
      stronger adsorption ability to the metal adatoms than the ordinary graphene
      lattice point. In the present work, by developing an analytical lattice Green's
      function technique, we theoretically study the RKKY interaction in graphene when
      two magnetic impurities are adsorbed near the line defect. We find that R(-3)
      decay rate of the RKKY interaction unique to graphene still holds true in the
      presence of the line defect. But another feature of the RKKY interaction in
      graphene, referred to as the Saremi's rule, which claims the RKKY interactions
      between the same or opposite sublattice points are ferro- or antiferromagnetic
      respectively, is no longer preserved due to the influence of the boundary state
      around the line defect. More importantly, the RKKY interaction on the line defect
      is greater than its counterpart in the pristine graphene by about one or two
      orders of magnitude. The local lattice distortion around the line defect can
      bring about the transition of the RKKY interaction between ferro- and
      antiferromagnetic orders. Such a result implies that the presence of the extended
      line defect provides a feasible platform in graphene to realize the long-range
      magnetic order even at a high temperature. 

PMID- 25566945
TI  - Impact of medications on cognitive function in obstructive sleep apnea syndrome.
AB  - PURPOSE: Medications can impact cognitive function. Obstructive sleep apnea
      syndrome (OSAS) is associated with cognitive impairment. There is currently a
      paucity of data evaluating the impact of medications on sleep architecture and
      cognition in untreated OSAS. Our objective was to evaluate the impact of
      obstructive sleep apnea syndrome (OSAS) and medications on cognition by a
      screening questionnaire called the Mail-In Cognitive Function Screening
      Instrument (MCFSI). METHODS: We conducted a retrospective chart review on
      consecutive adults (age > 18 years) with OSAS seen in Medical University of South
      Carolina Sleep Clinic between January 1, 2012 and May 8, 2013, for whom the Mail
      In Cognitive Function Screening Instrument (MCFSI) score was available and who
      were not on continuous positive airway pressure (CPAP). The correlation between
      different medications, sleep study variables, and MCFSI scores was studied.
      RESULTS: Univariate analysis revealed that many medications had significant
      correlations with MCFSI scores, including antidepressants (p = 0.05),
      antipsychotics (p = 0.01), anxiolytics (p = 0.005), statins (p = 0.077) and
      narcotics (p = 0.006). The mean percentage of rapid eye movement (REM) sleep (p =
      0.04) and Epworth Sleepiness Scale (p = 0.01) were also significantly correlated
      with MCFSI scores. Multivariate analysis revealed that Epworth Sleepiness Scale
      and use of antipsychotics, narcotics, and anxiolytics correlated with higher
      MCFSI scores (worse cognition) and conversely that statin use was associated with
      improved cognition. CONCLUSIONS: Medications have a significant impact on
      cognitive function in OSAS. Thus, medication use should be considered in future
      studies of cognitive function in patients with OSAS.

PMID- 25566947
TI  - Previous Homelessness as a Risk Factor for Recovery from Serious Mental
      Illnesses.
AB  - This paper argues that the experience of homelessness is inherently traumatic and
      thus has the potential to affect the manifestation of mental illness. The
      experiences related to being homeless might act as specific and unique sources of
      vulnerability. This study included 424 people diagnosed with serious mental
      illnesses living in supported housing programs in South Carolina. Three
      hierarchical regression analyses measuring the impact of homelessness on three
      types of outcomes revealed the following: (1) ever experiencing homelessness as
      well as the amount of time spent homeless were related to higher levels of
      psychiatric distress, (2) ever experiencing homelessness was related to higher
      levels of reported alcohol use, and (3) total amount of time spent homeless was
      related to lower perceived recovery from mental illness. These findings suggest
      that experiencing homelessness might contribute to psychosocial vulnerability to
      negative mental health outcomes. Future investigations examining this concept of
      risk and vulnerability as a result of homelessness are in order. 

PMID- 25566948
TI  - The effects of maternal depression on child mental health problems based on
      gender of the child.
AB  - Depression is a common disorder among women with young children. Compared to non
      depressed mothers, depressed mothers tend to display less positive affection,
      provide less emotional support, and inconsistently respond to their child's every
      day and emotional needs. We examined the association between maternal depression
      and child (middle childhood) mental health problems according to the child's
      gender. This study was conducted between June and August 2006 on 3,911 subjects
      aged 7-12 years. The data for this study was collected through a questionnaire
      that included the Beck Depression Inventory (BDI) and Korean Child Behavior
      Checklist (K-CBCL). Most of the CBCL scores were higher for children in the
      depressed mother group. The two way ANOVAs (depressed group by gender) found
      girls to have significantly higher scores than boys on somatization. Children may
      experience somatic complaints when they also suffer from emotional disorders, and
      therefore must be observed closely.

PMID- 25566949
TI  - Structure elucidation and in vitro cytotoxicity of ochratoxin alpha amide, a new
      degradation product of ochratoxin A.
AB  - The mycotoxin ochratoxin A is a secondary metabolite occurring in a wide range of
      commodities. During the exposure of ochratoxin A to white and blue light, a
      cleavage between the carbon atom C-14 and the nitrogen atom was described. As a
      reaction product, the new compound ochratoxin alpha amide has been proposed based
      on mass spectrometry (MS) experiments. In the following study, we observed that
      this compound is also formed at high temperatures such as used for example during
      coffee roasting and therefore represents a further thermal ochratoxin A
      degradation product. To confirm the structure of ochratoxin alpha amide, the
      compound was prepared in large scale and complete structure elucidation via
      nuclear magnetic resonance (NMR) and MS was performed. Additionally, first
      studies on the toxicity of ochratoxin alpha amide were performed using
      immortalized human kidney epithelial (IHKE) cells, a cell line known to be
      sensitive against ochratoxin A with an IC50 value of 0.5 MUM. Using this system,
      ochratoxin alpha amide revealed no cytotoxicity up to concentrations of 50 MUM.
      Thus, these results propose that the thermal degradation of ochratoxin A to
      ochratoxin alpha amide might be a detoxification process. Finally, we present a
      sample preparation and a HPLC-tandem mass spectrometry (HPLC-MS/MS) method for
      the analysis of ochratoxin alpha amide in extrudates and checked its formation
      during the extrusion of artificially contaminated wheat grits at 150 and 180 
      degrees C, whereas no ochratoxin alpha amide was detectable under these
      conditions. 

PMID- 25566950
TI  - Integrative proteome and transcriptome analysis of extramedullary erythropoiesis
      and its reversal by transferrin treatment in a mouse model of beta-thalassemia.
AB  - Beta-thalassemia results from mutations of the beta-hemoglobin (Hbb) gene and
      reduced functional Hbb synthesis. Excess alpha-Hb causes globin chain
      aggregation, oxidation, cytoskeletal damage, and increased red blood cell
      clearance. These events result in anemia, altered iron homeostasis, and expansion
      of extramedullary erythropoiesis. Serum transferrin (Tf) is suggested to be an
      important regulator of erythropoiesis in murine models of thalassemia. The
      present study was conducted to establish a quantitative proteomic and
      transcriptomic analysis of transferrin-modulated extramedullary erythropoiesis in
      the spleen of wild type and thalassemic Hbb(th3/+) mice. Our LC-MS/MS protein
      analysis and mRNA sequencing data provide quantitative expression estimates of
      1590 proteins and 24,581 transcripts of the murine spleen and characterize key
      processes of erythropoiesis and RBC homeostasis such as the whole heme synthesis
      pathway as well as critical components of the red blood cell antioxidant systems
      and the proliferative cell cycling pathway. The data confirm that Tf treatment of
      nontransfused Hbb(th3/+) mice induces a systematic correction of these processes
      at a molecular level. Tf treatment of Hbb(th3/+) mice for 60 days leads to a
      complete molecular restoration of the normal murine spleen phenotype. These
      findings support further investigation of plasma-derived Tf as a treatment for
      thalassemia.

PMID- 25566952
TI  - Endoscopic evaluation of clinical response after preoperative chemoradiotherapy
      for lower rectal cancer: the significance of endoscopic complete response.
AB  - PURPOSE: The management of rectal cancer is a significant oncologic challenge
      because rectal cancer has a poor prognosis among the various types of colorectal
      cancer. There have been several recent reports on a nonoperative approach for
      advanced lower rectal cancer, and this may be best for local disease control.
      However, objective evaluation of tumor response after preoperative
      chemoradiotherapy has not been standardized. The purpose of this study is to
      evaluate our method of endoscopic evaluation of complete response. METHODS: This
      is a retrospective chart review. All patients received a long course of
      preoperative chemoradiotherapy (5-fluorouracil-based chemotherapy and 45-50.4 Gy)
      followed by radical surgical resection from May 2005 to March 2012 in The Cancer
      Institute Hospital of Japanese Foundation for Cancer Research. One hundred fifty
      seven patients were reviewed consecutively. Criteria for endoscopic complete
      response were defined with a focus on the degree of ulcer healing and pit pattern
      without magnification. RESULTS: Endoscopic CR (E-CR) evaluation with our
      definitions reflected histopathologic response evaluation with an accuracy of
      91.7 %, sensitivity of 27.8 %, specificity of 100 %, positive predictive value
      (PPV) of 100 %, and negative predictive value (NPV) of 91.4 % (p < 0.001). Our
      criteria of E-CR led all cases of y-clinical CR (ycCR) to pathological CR.
      CONCLUSIONS: Endoscopic evaluation focused on the degree of ulcer healing, and
      pit pattern without magnification is useful for judging ycCR.

PMID- 25566951
TI  - Complex anal fistula remains a challenge for colorectal surgeon.
AB  - AIM: Anal fistula is a common proctological problem to both patient and physician
      throughout surgical history. Several surgical and sphincter-sparing approaches
      have been described for the management of fistula-in-ano, aimed to minimize the
      recurrence and to preserve the continence. We aimed to systematically review the
      available studies relating to the surgical management of anal fistulas. MATERIAL
      AND METHODS: A Medline search was performed using the PubMed, Ovid, Embase, and
      Cochrane databases to identify articles reporting on fistula-in-ano management,
      aimed to find out the current techniques available, the new technologies, and
      their effectiveness in order to delineate a gold standard treatment algorithm.
      RESULTS: The management of low anal fistulas is usually straightforward, given
      that fistulotomy is quite effective, and if the fistula has been properly
      evaluated, continence disturbance is minimal. On the contrary, high complex
      fistulas are challenging, because cure and continence are directly competing
      priorities. CONCLUSIONS: Conventional fistula surgery techniques have their
      place, but new technologies such as fibrin glues, dermal collagen injection, the
      anal fistula plugs, and stem cell injection offer alternative approaches whose
      long-term efficacy needs to be further clarified in large long-term randomized
      trials.

PMID- 25566953
TI  - Redirecting metabolic flux in Saccharomyces cerevisiae through regulation of
      cofactors in UMP production.
AB  - Although it is generally known that cofactors play a major role in the production
      of different fermentation products, their role has not been thoroughly and
      systematically studied. To understand the impact of cofactors on physiological
      functions, a systematic approach was applied, which involved redox state
      analysis, energy charge analysis, and metabolite analysis. Using uridine 5'
      monophosphate metabolism in Saccharomyces cerevisiae as a model, we demonstrated
      that regulation of intracellular the ratio of NADPH to NADP(+) not only
      redistributed the carbon flux between the glycolytic and pentose phosphate
      pathways, but also regulated the redox state of NAD(H), resulting in a
      significant change of ATP, and a significantly altered spectrum of metabolic
      products. 

PMID- 25566954
TI  - Influence of short-term unweighing and reloading on running kinetics and muscle
      activity.
AB  - PURPOSE: In running, body weight reduction is reported to result in decreased
      lower limb muscle activity with no change in the global activation pattern
      (Liebenberg et al. in J Sports Sci 29:207-214). Our study examined the acute
      effects on running mechanics and lower limb muscle activity of short-term
      unweighing and reloading conditions while running on a treadmill with a lower
      body positive pressure (LBPP) device. METHOD: Eleven healthy males performed two
      randomized running series of 9 min at preferred speed. Each series included three
      successive running conditions of 3 min [at 100 % body weight (BW), 60 or 80 % BW,
      and 100 % BW]. Vertical ground reaction force and center of mass accelerations
      were analyzed together with surface EMG activity recorded from six major muscles
      of the left lower limb for the first and last 30 s of each running condition.
      Effort sensation and mean heart rate were also recorded. RESULT: In both running
      series, the unloaded running pattern was characterized by a lower step frequency
      (due to increased flight time with no change in contact time), lower impact and
      active force peaks, and also by reduced loading rate and push-off impulse.
      Amplitude of muscle activity overall decreased, but pre-contact and braking phase
      extensor muscle activity did not change, whereas it was reduced during the
      subsequent push-off phase. CONCLUSION: The combined neuro-mechanical changes
      suggest that LBPP technology provides runners with an efficient support during
      the stride. The after-effects recorded after reloading highlight the fact that 3
      min of unweighing may be sufficient for updating the running pattern.

PMID- 25566955
TI  - Oricola cellulosilytica gen. nov., sp. nov., a cellulose-degrading bacterium of
      the family Phyllobacteriaceae isolated from surface seashore water, and emended
      descriptions of Mesorhizobium loti and Phyllobacterium myrsinacearum.
AB  - A Gram-stain negative, strictly aerobic, rod-shaped, non-spore-forming, motile
      cellulolytic bacterium, designated strain CC-AMH-0(T), was isolated from surface
      seashore water of Hualien, Taiwan and subjected to polyphasic taxonomy. Strain CC
      AMH-0(T) exhibited enzymatic saccharification of cellulose and active growth
      particularly during log-phase under nutrient-limited conditions, whereas enhanced
      saccharification was found in the declining growth phase under copiotrophic
      conditions. The novel strain shared high pairwise 16S rRNA gene sequence
      similarities to Mesorhizobium loti USDA 3471(T) (96.2 %), Phyllobacterium
      myrsinacearum IAM 13584(T) (95.9 %), Hoeflea marina LMG 128(T) (94.0 %) and other
      Phyllobacteriaceae members. However, phylogenetic analyses based on 16S rRNA,
      atpD and recA gene sequences clearly distinguished strain CC-AMH-0(T) from other
      representatives of related genera. In addition, strain CC-AMH-0(T) was
      distinguished from the above mentioned species by significantly lacking
      phosphatidylcholine besides accommodating major amounts of
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmonomethylethanolamine
      and sulfoquinovosyldiacylglycerol; moderate amounts of phosphatidylethanolamine
      and trace amounts of an unidentified phospholipid, an unidentified aminolipid and
      an unidentified phosphoglycolipid. Strain CC-AMH-0(T) possessed C18:1 omega7c
      and/or C18:1 omega6c (summed feature 8) as predominant fatty acids, 63.3 mol% DNA
      G+C content and ubiquinone-10 (Q-10) as the sole respiratory quinone. On the
      basis of polyphasic taxonomic evidences, strain CC-AMH-0(T) is proposed to
      represent a novel genus and species of the family Phyllobacteriaceae, for which
      the name Oricola cellulosilytica gen. nov., sp. nov. is proposed. The type strain
      of the type species is CC-AMH-0(T) (=JCM 19534(T) =BCRC 80694(T)). Emended
      descriptions of M. loti and P. myrsinacearum are also proposed. 

PMID- 25566956
TI  - Okibacterium endophyticum sp. nov., a novel endophytic actinobacterium isolated
      from roots of Salsola affinis C. A. Mey.
AB  - A white bacterial strain, designated EGI 650022(T), was isolated from the roots
      of Salsola affinis C. A. Mey, collected from Urumqi City, Xinjiang, north-western
      China. The strain was found to be aerobic, Gram-stain positive, oxidase-positive
      and catalase-positive. Cells were non-motile and irregular rods. Growth occurred
      at NaCl concentrations between 0 and 7 % (w/v), temperatures between 5 and 45 
      degrees C, and pH 6.0-9.0. Phylogenetic analysis based on 16S rRNA gene sequence
      indicated that strain EGI 650022(T) belongs to a clade with the genera
      Okibacterium and Plantibacter in the family Microbacteriaceae. The novel strain
      EGI 650022(T) showed highest levels of 16S rRNA gene sequence similarity with
      members of the genera Okibacterium and Plantibacter (97.2-98.0 %). The cell-wall
      peptidoglycan contained glutamate, homoserine, glycine, alanine and lysine. The
      predominant menaquinones (MKs) were MK-11, MK-12 and MK-12 (H4). The polar lipid
      pattern comprised phosphatidylglycerol, diphosphatidylglycerol, two unknown
      glycolipids and two unknown phospholipids. The major fatty acids were anteiso
      C15:0 and anteiso-C17:0. The DNA G+C content was 66.0 mol%. The DNA-DNA
      relatedness values of strain EGI 650022(T) with Okibacterium fritillariae DSM
      12584(T), Plantibacter flavus DSM 14012(T) and Plantibacter auratus DSM 19586(T)
      were 39.7, 19.7 and 22.0 %. Based on phylogenetic, phenotypic, chemotaxonomic and
      DNA-DNA hybridization data, strain EGI 650022(T) is considered to represent a
      novel species of the genus Okibacterium, for which the name Okibacterium
      endophyticum sp. nov. is proposed; the type strain is EGI 650022(T) (=JCM
      30086(T) = KCTC 29492(T)). 

PMID- 25566957
TI  - Up-regulation of NF45 correlates with Schwann cell proliferation after sciatic
      nerve crush.
AB  - Nuclear factor (NF)45 (also known as interleukin enhancer-binding factor (ILF)2),
      is a transcription factor that interacts with NF90 to regulate gene expression.
      It has long been implicated in the regulation of cell proliferation. However, the
      role of NF45 in the process of peripheral nervous system regeneration after
      injury remains poorly understood. Herein, we investigated the spatiotemporal
      expression of NF45 in a rat sciatic nerve crush model. We detected the up
      regulated expression of NF45 in Schwann cell after sciatic nerve crush. What's
      more, the expression of the cell proliferation marker proliferating cell nuclear
      antigen (PCNA) exhibited a similar tendency with that of NF45. In cell cultures,
      we observed increased expression of NF45 during the process of TNF-alpha-induced
      Schwann cell proliferation, whereas the protein level of p21 was down-regulated.
      Interference of NF45 led to enhanced expression of p21 and also impaired
      proliferation of Schwan cells. Taken together, our data implicated that NF45 was
      up-regulated in the sciatic nerve after crush, which was associated with
      proliferation of Schwann cell. 

PMID- 25566958
TI  - Impact of multiple low-level anticholinergic medications on anticholinergic load
      of community-dwelling elderly with and without dementia.
AB  - BACKGROUND: Elderly people, particularly those with dementia, are sensitive to
      adverse anticholinergic drug effects. This study examines the prevalence of
      anticholinergic medication, and anticholinergic load and its predictors, in
      community-dwelling elderly patients (aged 75 years and older) in Australia.
      METHODS: A research nurse visited the home of each participant (n = 1,044),
      compiled a list of current medications, and assessed participants' cognitive
      status using a subsection of the revised Cambridge Examination for Mental
      Disorders of the Elderly (CAMCOG-R). Anticholinergic load was determined for each
      patient using the Anticholinergic Drug Scale (ADS). RESULTS: Multivariate
      analysis identified several patient factors that were associated with higher
      anticholinergic burden, including polypharmacy (i.e. taking five or more
      medications) (p < 0.001), increasing age (p = 0.018), CAMCOG-R dementia (p =
      0.003), depression (p = 0.003), and lower physical quality of life (p < 0.001).
      The dementia group (n = 86) took a significantly higher number of medications
      (4.6 vs. 3.9; p = 0.04), and had a significantly higher anticholinergic load (1.5
      vs. 0.8; p = 0.002) than those without dementia (n = 958). Approximately 60% of
      the dementia group and 40% of the non-dementia group were receiving at least one
      anticholinergic drug. This difference was due to the higher proportion of
      dementia patients taking level 1 (potentially anticholinergic) (p = 0.002) and
      level 3 (markedly anticholinergic) (p = 0.005) drugs. CONCLUSIONS: There is
      considerable scope for the improvement of prescribing practices in the elderly,
      and particularly those with dementia. Importantly, level 1 anticholinergics have
      been identified as major contributors to the anticholinergic load in people with
      dementia. Longitudinal studies are required to determine the effects of increased
      and decreased anticholinergic load on cognitive function and other clinical
      outcomes for people with dementia.

PMID- 25566959
TI  - Establishment and characterization of a bladder cancer cell line with enhanced
      doxorubicin resistance by mevalonate pathway activation.
AB  - Resistance to chemotherapy is a major problem in the treatment of urothelial
      bladder cancer. Several mechanisms have been identified in resistance to
      doxorubicin by analysis of resistant urothelial carcinoma (UC) cell lines,
      prominently activation of drug efflux pumps and diminished apoptosis. We have
      derived a new doxorubicin-resistant cell line from BFTC-905 UC cells, designated
      BFTC-905-DOXO-II. A doxorubicin-responsive green fluorescent protein (GFP)
      reporter assay indicated that resistance in BFTC-905-DOXO-II was not due to
      increased drug efflux pump activity, whereas caspase-3/7 activation was indeed
      diminished. Gene expression microarray analysis revealed changes in proapoptotic
      and antiapoptotic genes, but additionally induction of the mevalonate
      (cholesterol) biosynthetic pathway. Treatment with simvastatin restored
      sensitivity of BFTC-905-DOXO-II to doxorubicin to that of the parental cell line.
      Induction of the mevalonate pathway has been reported as a mechanism of
      chemoresistance in other cancers; this is the first observation in bladder
      cancer. Combinations of statins with doxorubicin-containing chemotherapy regimens
      may provide a therapeutic advantage in such cases. 

PMID- 25566960
TI  - Oxidized low-density lipoprotein is associated with advanced-stage prostate
      cancer.
AB  - Clinical and epidemiological data suggest coronary artery disease shares etiology
      with prostate cancer (PCa). The aim of this work was to assess the effects of
      several serum markers reported in cardiovascular disease on PCa. Serum markers
      (oxidized low-density lipoprotein [ox-LDL], apolipoprotein [apo] B100, and
      apoB48) in peripheral blood samples from 50 patients from Fudan University
      Shanghai Cancer Center (FUSCC) with localized or lymph node metastatic PCa were
      investigated in this study. Twenty-five samples from normal individuals were set
      as controls. We first conducted enzyme-linked immunosorbent assay analysis to
      select candidate markers that were significantly different between these patients
      and controls. Then, the clinical relevance between OLR1 (the ox-LDL receptor)
      expression and PCa was analyzed in The Cancer Genome Atlas (TCGA) cohort. We also
      investigated the function of ox-LDL in PCa cell lines in vitro. Phosphorylation
      protein chips were used to analyze cell signaling pathways in ox-LDL-treated PC-3
      cells. The ox-LDL level was found to be significantly correlated with N stage of
      prostate cancer. OLR1 expression was correlated with lymph node metastasis in the
      TCGA cohort. In vitro, ox-LDL stimulated the proliferation, migration, and
      invasion of LNCaP and PC-3 in a dose-dependent manner. The results of
      phosphoprotein microarray illustrated that ox-LDL could influence multiple
      signaling pathways of PC-3. Activation of proliferation promoting signaling
      pathways (including beta-catenin, cMyc, NF-kappaB, STAT1, STAT3) as well as
      apoptosis-associating signaling pathways (including p27, caspase-3) demonstrated
      that ox-LDL had complicated effects on prostate cancer. Increased serum ox-LDL
      level and OLR1 expression may indicate advanced-stage PCa and lymph node
      metastasis. Moreover, ox-LDL could stimulate PCa proliferation, migration, and
      invasion in vitro. 

PMID- 25566961
TI  - Activation of FGF receptor signaling promotes invasion of non-small-cell lung
      cancer.
AB  - The molecular regulation of metastasis of non-small-cell lung cancer (NSCLC)
      remains not completely defined. Here we showed significant higher MMP26 in the
      resected NSCLC than adjacent healthy tissue from the patients. Moreover, a strong
      correlation between MMP26 and the phosphorylated fibroblast growth factor
      receptor 1 (FGFR1) was detected. To examine the causal relationship between
      activated FGFR signaling and MMP26, we studied a human NSCLC cell line, A549. We
      found that FGF1-induced FGFR1 phosphorylation in A549 cells activated MMP26,
      resulting in an increase in cancer invasiveness. Inhibition of FGFR1
      phosphorylation abolished FGF1-stimulated MMP26 activation, suggesting that
      activation of FGFR signaling pathway in NSCLC promotes cancer metastasis through
      MMP26. To define the signal transduction cascades downstream of FGFR1 activation
      for MMP26 activation, we used specific inhibitors for PI3K, ERK/MAPK, and JNK,
      respectively, to the FGF1-stimulated A549 cells. We found that only inhibition of
      JNK significantly decreased the activation of MMP26 in response to FGF1
      stimulation, suggesting that activation of FGFR1 signaling may activate JNK to
      activate MMP26 in NSCLC. Our study thus highlights FGFR signaling pathway and
      MMP26 as novel therapeutic targets for NSCLC therapy. 

PMID- 25566962
TI  - The 7th AJCC/UICC TNM staging system may be not suitable in predicting prognosis
      of synchronous multiple gastric carcinoma patients with D2 gastrectomy.
AB  - To assess the suitability of the 7th AJCC/UICC TNM staging system in predicting
      the prognosis of synchronous multiple gastric carcinomas (SMGCs). A total of 129
      SMGC patients who underwent gastrectomy with D2 lymphadenectomy from January 1999
      to January 2009 were enrolled in this study. The location, diameter, and depth of
      invasion of the main tumor were all related to prognosis (P < 0.05). Multivariate
      analysis revealed depth of invasion as an independent predictive factor for
      survival (P < 0.05). Interestingly, logistic regression analysis showed that the
      7th AJCC/UICC N staging system was unable to significantly predict survival in
      SMGCS patients (P > 0.05). Cut-point survival analysis identified the most
      appropriate cut-offs for metastatic lymph nodes (MLNs) as 0, 1, 6, 10, and 19:
      patients with 0, 1-6, 7-10, and 11-19, and >= 20 MLNs had median survival times
      of 70, 56, 35, 52, and 32 months, respectively. Multivariate analysis suggested
      this new categorization of MLNs to be a significant predictor of survival (P <
      0.05). Preoperative assessment of depth of invasion can help in the prognosis of
      SMGCs patients. The 7th UICC TNM staging system may be not suitable for SMGC
      patients and needs improvement for rational grading of SMGCs.

PMID- 25566963
TI  - IL-6 polymorphism in non-small cell lung cancer: a prognostic value?
AB  - Lung cancer was found to be the most commonly diagnosed cancer, as well as the
      primary cause of cancer-related mortality for males worldwide and the second
      leading cause of cancer-related deaths for women. Cytokines are fundamental for
      several biological processes-associated malignant tumors. The IL-6 is a cytokine
      involved in the regulation of cellular functions including processes associated
      with cancer, such as proliferation, apoptosis, angiogenesis, and differentiation.
      Furthermore, IL-6 is a potent pleiotropic inflammatory cytokine that is
      considered a key growth-promoting and antiapoptotic factor. The polymorphism
      174G/C SNP is a G to C transition in the -174 position of the promoter region of
      the IL-6 gene. The aim of our study was to evaluate the influence of -174G/C
      polymorphism in clinical outcome of non-small cell cancer (NSCLC) patients. DNA
      was extracted from peripheral blood of 424 patients diagnosed with cytologically
      or histologically NSCLC. The characterization of IL-6 -174G/C genotypes was
      performed by PCR-RFLP (NlaIII). IL-6 polymorphism's genotypes were divided
      according to functional activity, so the G carriers (CG/GG) is the high-producer
      IL-6, and CC genotype is the low-producer IL-6. Regarding survival, we verify
      that patients with genotypes carrying the G allele (CG/GG) had a statistically
      significant diminished survival when compared with patients with CC genotype
      (62.79 and 42.31 months, respectively; P = 0.032). In the promoter region of the
      IL-6 gene, polymorphic variants were located and may be responsible for
      alterations in transcription that consequently affect serum levels of the
      cytokine. With our study, we demonstrated that genetic variant (-174G/G and G/C)
      can be responsible for changes in prognosis of NSCLC patients.

PMID- 25566964
TI  - Polymorphisms in the MTHFR gene are associated with breast cancer risk and
      prognosis in a Chinese population.
AB  - Breast cancer is the most common cancer affecting women in China and the world.
      Folate supplementation is proven to be effective in reducing the risk of breast
      cancer or improving its prognosis. Methylenetetrahydrofolate reductase (MTHFR) is
      an important enzyme involved in folate metabolism and DNA synthesis. This study
      aims to examine whether single nucleotide polymorphisms (SNP) in the MTHFR gene
      are associated with risk and survival of breast cancer and serum folate levels in
      healthy controls. We genotyped nine tagging SNPs in the MTHFR gene in a case
      control study, including 560 breast cancer cases and 560 healthy controls in
      China. We found that TT genotype of rs1801133 had significant increased risk of
      breast cancer [adjusted odds ratio (OR) = 1.60, 95 % confidence interval (CI)
      1.12-2.28] compared with CC genotype, and CC genotype of rs9651118 conferred
      significant reduced risk of breast cancer (adjusted OR = 0.65, 95 % CI 0.45-0.95)
      compared to TT genotype. Haplotype analysis also showed that MTHFR CACCAA and
      AGTCAC haplotypes (rs12121543-rs13306553-rs9651118-rs1801133-rs4846048-rs1801131)
      had significant reduced risk of breast cancer (adjusted OR = 0.70, 95 % CI 0.58
      0.86; adjusted OR = 0.57, 95 % CI 0.40-0.80) compared with CATTAA haplotype.
      Besides, MTHFR rs9651118 CC genotype was significantly associated with survival
      in breast cancer cases (adjusted hazard ratio (HR) = 0.63, 95 % CI 0.40-0.99).
      But none of the SNPs in the MTHFR gene was associated with serum folate level in
      healthy controls. These findings suggest that variants in the MTHFR gene may
      influence the risk and prognosis of breast cancer.

PMID- 25566965
TI  - Regulation of growth of human bladder cancer by miR-192.
AB  - The regulation of microRNA-192 (miR-192) is impaired in many cancers. Here, we
      investigated the role of miR-192 in the proliferation, cell cycle progression,
      and apoptosis of bladder cancer cells. Human bladder cancer cells were
      transfected with human miR-192 precursor or non-specific control miRNA. The
      effect of miR-192 on cell proliferation was assessed by a MTT assay. The effects
      of miR-192 on cell cycle regulation and apoptosis were evaluated by flow
      cytometry. Western blot was used to analyze the protein levels of cyclin D1, p21,
      p27, Bcl-2, Bax, and Mcl-1. We found that overexpression of miR-192 significantly
      decreased the proliferation of bladder cancer cells by 22 and 54 % at 48 and 72
      h, respectively. MiR-192-overexpressing cells exhibited a significant increase in
      G0/G1 phase and a significant decrease in S phase compared to the control miRNA
      transfected cells. Moreover, overexpression of miR-192 significantly induced
      apoptotic death in bladder cancer cells, increased the levels of p21, p27, and
      Bax, and decreased the levels of cyclin D1, Bcl-2, and Mcl-1. Taken together,
      these data suggest that miR-192 may be a suppressor for bladder cancer cells by
      cell cycle regulation.

PMID- 25566966
TI  - Demethylation-mediated miR-129-5p up-regulation inhibits malignant phenotype of
      osteogenic osteosarcoma by targeting Homo sapiens valosin-containing protein
      (VCP).
AB  - Previous studies demonstrated that increased Homo sapiens valosin-containing
      protein (VCP) may be involved in osteosarcoma (OS) metastasis. However, the
      underlying mechanism of VCP over-expression in OS remains unknown. In the present
      study, we found a significantly negative correlation between miR-129-5p and VCP
      protein expression in OS tissues with pulmonary metastasis (Spearman's rho, rs = 
      0.948). Bioinformatical prediction, Luciferase reporter assay, Western blot, and
      RT-PCR assays performed on OS cells indicated that VCP is a target of miR-129-5p.
      In addition, three CPG islands in the region of miR-129-5p promoter were detected
      by bioinformatical prediction, and significantly higher expression of miR-129-5p
      and lower methylation level of miR-129-2 gene in OS cells treated with 5-Aza-2'
      deoxycytidine (a potent DNA demethylating agent) than in those untreated cells
      were observed. Furthermore, lower migratory and invasive ability was found in
      cells with elevated miR-129-5p than in those with decreased miR-129-5p. These
      findings indicated that increased miR-129-5p may be mediated by demethylation and
      inhibit OS cell migration and invasion by targeting VCP in OS, and targeting miR
      129-5p/VCP signaling pathway may serve as a therapeutic strategy for OS
      management, although further studies will be necessary. 

PMID- 25566967
TI  - Fenofibrate induces G0/G1 phase arrest by modulating the PPARalpha/FoxO1/p27 kip
      pathway in human glioblastoma cells.
AB  - Fenofibrate, a fibric acid derivative, is known to possess lipid-lowering
      effects. Although fenofibrate-induced peroxisome proliferator-activated receptor
      alpha (PPARalpha) transcriptional activity has been reported to exhibit
      anticancer effects, the underlying mechanisms are poorly understood. In this
      study, we investigated the mechanisms behind the antiproliferative effects of
      fenofibrate in U87MG cells (human glioma cell line) using the WST-8 Cell
      Proliferation Assay Kit. Furthermore, we examined genome-wide gene expression
      profiles and molecular networks using the DAVID online software. Fenofibrate
      reduced the expression of 405 genes and increased the expression of 2280 genes.
      DAVID analysis suggested that fenofibrate significantly affected cell cycle
      progression and pathways involved in cancer, including the mTOR signaling pathway
      and insulin signaling pathway. Results of flow cytometry analysis indicated that
      fenofibrate induced cell cycle G0/G1 arrest in U87MG cells. Furthermore, we
      identified the FoxO1-p27(kip) signaling axis to be involved in fenofibrate
      induced cell cycle arrest. Our findings suggest that in addition to its known
      lipid-lowering effects, fenofibrate may be used as an antitumor agent in glioma
      therapy. 

PMID- 25566968
TI  - Percutaneous balloon kyphoplasty of malignant lesions of the spine: a prospective
      consecutive study in 115 patients.
AB  - PURPOSE: To evaluate the benefits of minimally invasive balloon kyphoplasty (BKP)
      in patients with cancer and painful pathologic vertebral lesions. METHODS: In
      this longitudinal, prospective, consecutive study, patients received BKP at one
      or more vertebral levels. The BKP procedure was guided by computed tomographic
      fluoroscopy. Orthopaedic bone tamps were inflated to create a cavity and the
      fracture was stabilised using viscous polymethylmethacrylate bone cement. After
      the procedure, early mobilisation was encouraged. RESULTS: Overall, 115 patients
      (52.2% with vertebral fractures) received BKP. The majority (82.6%) of patients
      received BKP as a stand-alone procedure. BKP treatment provided significant
      (P<0.0001) improvements in Visual Analogue Scale (VAS)-pain (median change: -4),
      Oswestry Disability Index (ODI; mean change: -53.2), and Karnofsky Performance
      Status (KPS; median change: 15) scores at 6 and 12 months. In total, 23% of
      patients achieved increased vertebral height (7.4% mean improvement in angle
      index). The presence of height restoration and the number of levels treated did
      not affect VAS or ODI scores; improvements in KPS scores were numerically higher
      in patients who received BKP plus additional surgery (15-20) compared with stand
      alone BKP (10-15). Mean hospital times were 7.2+/-6.5 days. The majority (97.4%)
      of patients showed no complications related to the procedure; three patients
      (2.6%) had a temporary radiculopathy. Incidences of cement leakage were observed
      in 40 patients (34.8%). CONCLUSIONS: Minimally invasive BKP provided excellent
      long-term palliation of pain and improved mobility in patients with cancer and
      painful osteolytic spinal lesions or vertebral fractures.

PMID- 25566969
TI  - Hypervascular cervical spine metastases: embolization by direct injection of Onyx
      18.
AB  - PURPOSE: Spinal metastases are common in patients with cancer. Following lung and
      liver, spine is the most common site for cancers to metastasize. Many of them are
      hypervascularized. These cases are a particular challenge for the surgeon and
      represent a significant danger of massive blood loss during surgery.
      Hypervascularized metastases of the cervical spine also include the risk of
      postoperative bleeding with severe neurological impairment. We report a case of a
      67-year-old women with breast cancer (BC) metastasis within the vertebral bodies
      of C3 and C4 with nearly complete bony destruction of the ventral column and
      intraspinal tumor masses compressing the spinal cord at level C3 and C4. The
      hypervascularized tumor was supplied by multiple minor vessels from both
      vertebral arteries, too small to be coiled individually. Due to an allergy to
      aspirin, intravascular stenting of the vertebral arteries was not an option. We
      decided to perform a preoperative direct injection of onyx-18 for embolization of
      the tumor. CONCLUSION: Presurgical direct injection of Onyx-18 for treating
      hypervascular spinal metastases of breast cancer seems to be an effective and
      safe technique and reduces intraoperative bleeding to a minimum.

PMID- 25566970
TI  - Associations analysis of GSTM1, T1 and P1 Ile105Val polymorphisms with carpal
      tunnel syndrome.
AB  - Oxidative stress was related with carpal tunnel syndrome (CTS). We aimed to
      clarify the associations between glutathione S-transferase (GST)M1, GSTT1 and
      GSTP1-Ile105Val polymorphisms and CTS. One hundred-forty patients with CTS and 97
      healthy controls were enrolled in this study. Tinel and Phalen signs were noted
      as positive or negative. Functional and clinical status of patients was evaluated
      by the Boston Questionnaire. The intensity of hand and/or wrist pain was
      evaluated on 10 cm visual analog scale (VAS). We applied the polymerase chain
      reaction (PCR) to determine the polymorphisms of the GSTM1 and GSTT1 and the PCR
      restriction fragment length polymorphism method for detecting the GSTP1-Ile105Val
      polymorphism. The M1 null genotype was significantly higher in patients with CTS
      compared to healthy controls, and the M1 null genotype seemed to increase the
      risk of CTS approximately two-fold (P = 0.011; odds ratio (OR) = 1.98; 95 %
      confidence interval (CI) 1.17-3.36). The M1 null, T1 present combined genotype
      was significantly higher in patients with CTS compared to healthy controls (P =
      0.043); however, it seemed not to increase the risk of CTS (P = 0.14; OR = 0.62;
      95 % CI 0.33-1.76). We found significantly higher levels of the VAS, Boston
      Symptom Severity Scale and Phalen sign in patients with the Ile/Val or the
      Val/Val genotypes compared to those in patients with the Ile/Ile genotype (P =
      0.003, 0.004 and 0.044, respectively). We proposed that genes involved in the
      protection from oxidative stress may influence the susceptibility, clinical and
      functional status of CTS. The GSTM1 null genotype may be related with the
      development of CTS, whereas the Val allele of GSTP1-Ile105Val polymorphism may be
      associated with worse functional and clinical status in CTS. 

PMID- 25566973
TI  - Highly stable and sensitive LnMOF ratiometric thermometers constructed with mixed
      ligands.
AB  - The mixed-lanthanide metal-organic frameworks (M'LnMOFs) applied for accurate,
      non-invasive and self-reference temperature measurements have been only recently
      recognized. It is a great challenge for chemists to fulfil the requirements of a
      thermostable structure, intense luminescence and high temperature sensitivity on
      one LnMOF ratiometric thermometer for thermometric applications. By choosing 2,4
      (2,2':6',2''-terpyridin-4'-yl)-benzenedisulfonic acid (H2DSTP) as the first
      ligand and changing the ancillary ligand to oxalic acid (OA) or 1,4-benzene
      dicarboxylic acid (BDC), we have successfully developed two types of highly
      stable and sensitive thermometers [Tb1-xEux(OA)0.5(DSTP)].3H2O and [Tb1
      xEux(BDC)0.5(DSTP)].2H2O (x = 0.01, 0.02) that in addition exhibit brilliant
      luminescence over a wide temperature range, providing a new strategy to explore
      luminescence-based M'LnMOF thermometers. 

PMID- 25566971
TI  - Uncovering the emotional aspects of working on a clinical trial: a qualitative
      study of the experiences and views of staff involved in a type 1 diabetes trial.
AB  - BACKGROUND: The perspectives and experiences of trial staff are increasingly
      being investigated as these can be used to improve recruitment, adherence to
      trial protocols and support given to future staff. We interviewed staff working
      on a type 1 diabetes trial in order to aid interpretation of trial findings,
      inform recommendations for the rollout of the treatments investigated and provide
      recommendations for the conduct of future trials. However, our interviews
      uncovered aspects of trial work erstwhile unrecognised or underreported in the
      trials literature, and it is these which form the focus of this paper. METHODS:
      In-depth interviews were conducted with (n = 18) staff, recruited from seven
      centres, who were involved in recruitment and trial delivery. Data were analysed
      thematically. RESULTS: Alongside logistical and practical issues which made trial
      work challenging, staff often talked spontaneously and at length about how trial
      work had affected them emotionally. Staff not only described the emotional
      stresses arising from having to meet recruitment targets and from balancing
      research roles with clinical responsibilities, they also discussed having to
      emotionally manage patients and their colleagues. The emotional aspects of trial
      work particularly came to the fore when staff notified patients about their
      treatment allocation. On such occasions, staff described having to employ
      emotional strategies to pre-empt and manage potential patient disappointment and
      anger. Staff also described having to manage their own emotions when patients
      withdrew from the trial or were not randomised to the treatment arm which, in
      their clinical judgment, would have been in their best interests. To help address
      the emotional challenges they encountered, staff highlighted a need for more
      practical, emotional and specialist psychological support. CONCLUSIONS: More
      attention should be paid to the emotional aspects of trial work to help ensure
      trial staff are adequately supported. Such support could comprise: increased
      training for staff to improve their own and patients' understandings of
      randomization, role-play to develop techniques to manage patient anger and
      disappointment, sharing of good practice, formalised team support with
      psychological input and access to specialist psychological support to
      troubleshoot complex emotional and ethical issues.

PMID- 25566972
TI  - Amphetamine self-administration and dopamine function: assessment of gene *
      environment interactions in Lewis and Fischer 344 rats.
AB  - RATIONALE: Previous research suggests both genetic and environmental influences
      on substance abuse vulnerability. OBJECTIVES: The current work sought to
      investigate the interaction of genes and environment on the acquisition of
      amphetamine self-administration as well as amphetamine-stimulated dopamine (DA)
      release in nucleus accumbens shell using in vivo microdialysis. METHODS: Inbred
      Lewis (LEW) and Fischer (F344) rat strains were raised in either an enriched
      condition (EC), social condition (SC), or isolated condition (IC). Acquisition of
      amphetamine self-administration (0.1 mg/kg/infusion) was determined across an
      incrementing daily fixed ratio (FR) schedule. In a separate cohort of rats,
      extracellular DA and the metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were
      measured in the nucleus accumbens shell following an acute amphetamine injection
      (1 mg/kg). RESULTS: "Addiction-prone" LEW rats had greater acquisition of
      amphetamine self-administration on a FR1 schedule compared to "addiction
      resistant" F344 rats when raised in the SC environment. These genetic differences
      were negated in both the EC and IC environments, with enrichment buffering
      against self-administration and isolation enhancing self-administration in both
      strains. On a FR5 schedule, the isolation-induced increase in amphetamine self
      administration was greater in F344 than LEW rats. While no group differences were
      obtained in extracellular DA, gene * environment differences were obtained in
      extracellular levels of the metabolite DOPAC. In IC rats only, LEW rats showed
      attenuation in the amphetamine-induced decrease in DOPAC compared to F344 rats.
      IC LEW rats also had an attenuated DOPAC response to amphetamine compared to EC
      LEW rats. CONCLUSIONS: The current results demonstrate gene * environment
      interactions in amphetamine self-administration and amphetamine-induced changes
      in extracellular DOPAC in nucleus accumbens (NAc) shell. However, the behavioral
      and neurochemical differences were not related directly, indicating that
      mechanisms independent of DA metabolism in NAc shell likely mediate the gene *
      environment effects in amphetamine self-administration.

PMID- 25566974
TI  - Pilot simulation study using meat inspection data for syndromic surveillance: use
      of whole carcass condemnation of adult cattle to assess the performance of
      several algorithms for outbreak detection.
AB  - The objective of this study was to assess the performance of several algorithms
      for outbreak detection based on weekly proportions of whole carcass
      condemnations. Data from one French slaughterhouse over the 2005-2009 period were
      used (177 098 slaughtered cattle, 0.97% of whole carcass condemnations). The
      method involved three steps: (i) preparation of an outbreak-free historical
      baseline over 5 years, (ii) simulation of over 100 years of baseline time series
      with injection of artificial outbreak signals with several shapes, durations and
      magnitudes, and (iii) assessment of the performance (sensitivity, specificity,
      outbreak detection precocity) of several algorithms to detect these artificial
      outbreak signals. The algorithms tested included the Shewart p chart, confidence
      interval of the negative binomial model, the exponentially weighted moving
      average (EWMA); and cumulative sum (CUSUM). The highest sensitivity was obtained
      using a negative binomial algorithm and the highest specificity with CUSUM or
      EWMA. EWMA sensitivity was too low to select this algorithm for efficient
      outbreak detection. CUSUM's performance was complementary to the negative
      binomial algorithm. The use of both algorithms on real data for a prospective
      investigation of the whole carcass condemnation rate as a syndromic surveillance
      indicator could be relevant. Shewart could also be a good option considering its
      high sensitivity and simplicity of implementation. 

PMID- 25566975
TI  - A click chemistry approach to site-specific immobilization of a small laccase
      enables efficient direct electron transfer in a biocathode.
AB  - Controlled orientation of a small laccase on a multi-walled carbon nanotube
      electrode was achieved via copper-free click chemistry mediated immobilization.
      Modification of the enzyme was limited to only the tethering site and involved
      the genetic incorporation of the unnatural amino acid 4-azido-L-phenylalanine
      (AzF). This approach enabled efficient direct electron transfer.

PMID- 25566976
TI  - Intraoperative frozen section for the evaluation of extrathyroidal extension in
      papillary thyroid cancer.

PMID- 25566977
TI  - Antimicrobial prophylaxis for the prevention of surgical site infection after
      thyroid and parathyroid surgery: a prospective randomized trial.
AB  - BACKGROUND AND OBJECTIVE: The effectiveness of antimicrobial prophylaxis (AMP) in
      the prevention of surgical site infection (SSI) following thyroid and parathyroid
      surgery remains uncertain. The objective of this prospective randomized
      controlled trial (Ito-RCT1) was to assess the effectiveness of AMP in clean neck
      surgery performed to treat thyroid and parathyroid disease. METHODS: Participants
      comprised patients scheduled for clean neck surgery for thyroid and parathyroid
      disease at Ito Hospital. Patients whose surgery included sternotomy or resection
      of the trachea, larynx, pharynx, or esophagus were excluded. AMP consisted of 2 g
      of piperacillin (PIPC) (group A, n = 541) or 1 g of cefazolin (CEZ) (group B, n =
      541) administered intravenously immediately after endotracheal intubation.
      Patients in the control group (Group C, n = 1,082) did not receive AMP. RESULTS:
      Statistical analysis was performed to compare the AMP group (Group A + Group B)
      with the control group (Group C). Drug-induced acute reactions correlated to PIPC
      or CEZ did not occur in the AMP group. No significant differences in the
      postoperative incidence of liver or renal dysfunction were seen between the AMP
      and control groups. Postoperative incidence of urinary tract infection was
      significantly higher in the control group (p = 0.002). The incidence of SSI
      events was very low, with only 1 event (0.09 %) in the AMP group and 3 events
      (0.28 %) in the control group, and this difference between groups was not
      significant (p = 0.371). CONCLUSIONS: AMP is not necessary to prevent SSI after
      clean thyroid or parathyroid surgery.

PMID- 25566978
TI  - Major liver resection as definitive treatment in post-cholecystectomy common bile
      duct injuries.
AB  - BACKGROUND: Common bile duct injuries (CBDI) are serious complications of
      cholecystectomies which are often associated with vascular involvement, meaning
      that their management represents a major challenge to the physician. We present
      our experience in major hepatectomy due to CBDI, highlighting indications,
      postoperative complications, and long-term outcomes. METHODS: From August 1993 to
      September 2013, 287 patients with CBDI were treated in our centre. In 15 patients
      of this group (5 %), a major hepatectomy was performed. Eleven patients presented
      E4 and four presented E5 injuries of Strasberg classification. Seven patients
      presented vascular involvement. In 12 patients, prior treatment attempts, either
      biliodigestive anastomosis, endoscopic or percutaneous drainage, was performed
      without success. The median time delay between lesional surgery and hepatectomy
      was 24 months. RESULTS: Right hepatectomy was performed in 10 patients and left
      hepatectomy in 5. Postoperative morbidity was 60 %. The incidence of serious
      complications (>= grade IIIa of DC classification) was 40 %. There was no
      mortality in our study. The mean follow-up was 43.5 months and the overall
      survival was 100 %. Three patients had a single episode of ascendant cholangitis
      who were successfully treated with medical treatment. All other patients were
      asymptomatic during follow-up. No patients required further surgical procedures.
      CONCLUSION: In our series, major hepatectomy due to CBDI was a successful
      treatment with high rates of postoperative morbidity and excellent long-term
      outcomes which require a multidisciplinary approach in referral centres of HPB
      surgery.

PMID- 25566979
TI  - Essential surgery: the way forward.
AB  - INTRODUCTION: Very little surgical care is performed in low- and middle-income
      countries (LMICs). An estimated two billion people in the world have no access to
      essential surgical care, and non-surgeons perform much of the surgery in remote
      and rural areas. Surgical care is as yet not recognized as an integral aspect of
      primary health care despite its self-demonstrated cost-effectiveness. We aimed to
      define the parameters of a public health approach to provide surgical care to
      areas in most need. METHODS: Consensus meetings were held, field experience was
      collected via targeted interviews, and a literature review on the current state
      of essential surgical care provision in Sub-Saharan Africa (SSA) was conducted.
      Comparisons were made across international recommendations for essential surgical
      interventions and a consensus-driven list was drawn up according to their
      relative simplicity, resource requirement, and capacity to provide the highest
      impact in terms of averted mortality or disability. RESULTS: Essential Surgery
      consists of basic, low-cost surgical interventions, which save lives and prevent
      life-long disability or life-threatening complications and may be offered in any
      district hospital. Fifteen essential surgical interventions were deduced from
      various recommendations from international surgical bodies. Training in the realm
      of Essential Surgery is narrow and strict enough to be possible for non-physician
      clinicians (NPCs). This cadre is already active in many SSA countries in
      providing the bulk of surgical care. CONCLUSION: A basic package of essential
      surgical care interventions is imperative to provide structure for scaling up
      training and building essential health services in remote and rural areas of
      LMICs. NPCs, a health cadre predominant in SSA, require training, mentoring, and
      monitoring. The cost of such training is vastly more efficient than the expensive
      training of a few polyvalent or specialist surgeons, who will not be sufficient
      in numbers within the next few generations. Moreover, these practitioners are
      used to working in the districts and are much less prone to gravitate elsewhere.
      The use of these NPCs performing "Essential Surgery" is a feasible route to deal
      with the almost total lack of primary surgical care in LMICs.

PMID- 25566980
TI  - Moving from data collection to application: a systematic literature review of
      surgical capacity assessments and their applications.
AB  - BACKGROUND: Over the past decade, assessments of surgical capacity in low- and
      middle-income countries (LMICs) have contributed to our understanding of barriers
      to the delivery of surgical services in a number of countries. It is yet unclear,
      however, how the findings of these assessments have been applied and built upon
      within the published literature. METHODS: A systematic literature review of
      surgical capacity assessments in LMICs was performed to evaluate current levels
      of understanding of global surgical capacity and to identify areas for future
      study. A reverse snowballing method was then used to follow-up citations of the
      identified studies to assess how this research has been applied and built upon in
      the literature. RESULTS: Twenty-one papers reporting the findings of surgical
      capacity assessments conducted in 17 different LMICs in South Asia, East Asia and
      Pacific, Latin America and the Caribbean, and sub-Saharan Africa were identified.
      These studies documented substantial deficits in human resources, infrastructure,
      equipment, and supplies. Only seven additional papers were identified which
      applied or built upon the studies. Among these, capacity assessment findings were
      most commonly used to develop novel tools and intervention strategies, but they
      were also used as baseline measurements against which updated capacity
      assessments were compared. CONCLUSIONS: While the global surgery community has
      made tremendous progress in establishing baseline values of surgical capacity in
      LMICs around the world, further work is necessary to build upon and apply the
      foundational knowledge established through these efforts. Capacity assessment
      data should be coordinated and used in ongoing research efforts to monitor and
      evaluate progress in global surgery and to develop targeted intervention
      strategies. Intervention strategy development may also be further incorporated
      into the evaluation process itself.

PMID- 25566981
TI  - Laparoscopic Heller myotomy and fundoplication in patients with end-stage
      achalasia.
AB  - Achalasia may present in a non-advanced or advanced (end stage) stage. The latter
      is characterized by massive esophageal dilatation and/or the loss of the
      esophageal straight axis (sigmoid-shaped esophagus). The treatment for non
      advanced cases of achalasia is well defined while the therapy for end-stage
      disease is still debatable. Laparoscopic Heller's myotomy is an option in
      patients with end-stage achalasia. Dysphagia is relieved in a significant number
      of patients, it is a simpler operation to be used in frail patients, and it does
      not preclude a latter esophagectomy if necessary. 

PMID- 25566982
TI  - The future of breast cancer systemic therapy: the next 10 years.
AB  - Over the past 50 years, substantial progress has been made in the systemic
      treatment of early-stage and advanced breast cancer. The use of chemotherapy in
      the adjuvant and metastatic settings has demonstrated proven efficacy and it has
      been clearly demonstrated that targeting the estrogen receptor and human growth
      factor receptor 2 (HER2) is efficacious in early and advanced disease. Despite
      these advances, vexing clinical challenges remain particularly related to the
      treatment of triple-negative breast cancer (TNBC; estrogen receptor [ER]
      negative, progesterone receptor [PR]-negative, and HER2-negative) where little
      progress has been made therapeutically in more than a decade. While recurrences
      of hormone-responsive breast cancer are overall less common, late relapses after
      cessation of endocrine therapy are a more frequent occurrence in modern times and
      reflect the problem of underlying tumor dormancy that as yet has not been
      overcome. Multiple molecular tools are now available to interrogate the biology
      of breast cancer, though exactly how to make this information meaningful in the
      clinic has proven challenging, and molecularly driven clinical trials have faced
      feasibility challenges. In parallel, focus has expanded from tumor to host with
      the ability to ascertain underlying germline alterations, such as inherited BRCA1
      and BRCA2 mutations, which may be responsible for breast cancer carcinogenesis
      and, importantly, may have implications for treatment. These clinical advances in
      germline genetics, made possible by both scientific investigation as well as the
      courts, still face challenges related to increasing encounters with variants of
      unknown significance and difficulty in predicting risks associated with less well
      characterized inherited cancer predisposition syndromes. In this paper, we
      attempt to predict the next 10 years of breast cancer, in particular focusing on
      how the past serves as prologue to the future in this disease. 

PMID- 25566983
TI  - Synthesis, binding affinity and structure-activity relationships of novel,
      selective and dual targeting CCR2 and CCR5 receptor antagonists.
AB  - CCR2 and CCR5 receptors play a key role in the development and progression of
      several inflammatory, cardiovascular and autoimmune diseases. Therefore, dual
      targeting of both receptors appeals as a promising strategy for the treatment of
      such complex, multifactorial disorders. Herein we report on the design, synthesis
      and biological evaluation of benzo[7]annulene- and [7]annulenothiophene-based
      selective and dual CCR2 and CCR5 receptor antagonists. Intermediates were
      designed in such a way that diversification could be introduced at the end of the
      synthesis. Starting from the lead compound TAK-779 (1), the quaternary ammonium
      moiety was exchanged by different non-charged moieties, the 4-methylphenyl moiety
      was extensively modified and the benzo[7]annulene core was replaced
      bioisosterically by the [7]annulenothiophene system. The naphthyl derivative 9h
      represents the most promising dual antagonist (Ki (CCR2) = 25 nM, IC50 (CCR5) =
      17 nM), whereas the 6-isopropoxy-3-pyridyl and 4-methoxycarbonylphenyl
      derivatives 9k and 9r show more than 20-fold selectivity for the CCR2 (Ki = 19
      nM) over the CCR5 receptor.

PMID- 25566985
TI  - Validation of Koopmans' theorem for density functional theory binding energies.
AB  - Both initial state effects, to a good approximation the electrostatic potential
      at the nucleus, and final state effects, due to the response of the electrons to
      the presence of the core-hole, contribute to core-level binding energies, BE's.
      For Hartree-Fock, HF, wavefunctions, Koopmans' theorem, KT, which states that the
      initial state BE = -epsilon iotas rigorous. However, the KT relationship is
      commonly used for Kohn-Sham, KS, epsilon's. We review that the KT relationship
      with KS epsilon's fails to give the absolute initial state contribution to the
      BE. However, we demonstrate that the shifts of initial state BE's from a
      reference value are accurately obtained from the shifts of the KS epsilon's. Thus
      the initial state contributions to BE shifts can be obtained from KT using KS
      epsilon's. This result validates a large body of work where KT has been used with
      KS epsilon's to define initial state contributions to BE shifts. 

PMID- 25566984
TI  - Clinical experience of sleeve lobectomy with bronchoplasty using a continuous
      absorbable barbed suture.
AB  - Anastomosis in bronchoplasty is usually performed using interrupted sutures,
      which are considered safe, reliable, and secure. However, placing interrupted
      sutures can be complex and time-consuming. There have been recent reports of
      continuous suturing using standard suture materials in bronchoplasty. We have
      experienced four cases of sleeve lobectomy with bronchial anastomosis in
      continuous fashion using a novel absorbable barbed suture device, the V-LocTM
      wound closure device (Covidien, USA), which facilitates secure wound closure
      without knot-tying. Two patients underwent sleeve upper lobectomy and two
      underwent sleeve upper-middle lobectomy. Surgical approach was completely
      thoracoscopic in one patient and open in three. There were no intraoperative
      difficulties such as cutting or loosening, and a leak test was negative in all
      cases. One patient had pneumonia postoperatively and developed anastomotic
      stenosis 4 months after surgery, which did not require treatment. All patients
      were alive, without local recurrence, at a mean follow-up of 11.5 months
      postoperatively.

PMID- 25566986
TI  - Copper-palladium core-shell as an anode in a multi-fuel membraneless nanofluidic
      fuel cell: toward a new era of small energy conversion devices.
AB  - A membraneless nanofluidic fuel cell with flow-through electrodes that works with
      several fuels (individually or mixed): methanol, ethanol, glycerol and ethylene
      glycol in alkaline media is presented. For this application, an efficient Cu@Pd
      electrocatalyst was synthesized and tested, resulting outstanding performance
      until now reported, opening the possibility of power nano-devices for multi-uses
      purposes, regardless of fuel re-charge employed. 

PMID- 25566989
TI  - Nanoparticle-cored dendrimers: functional hybrid nanocomposites as a new platform
      for drug delivery systems.
AB  - Nanoparticle-cored dendrimers (NCDs) are now offering themselves as versatile
      carriers because of their colloidal stability, tunable membrane properties and
      ability to encapsulate or integrate a broad range of drugs and molecules. This
      kind of hybrid nanocomposite aims to combine the advantages of stimuli-responsive
      dendritic coatings, in order to regulate the drug release behaviour under
      different conditions and improve the biocompatibility and in vivo half-time
      circulation of the inorganic nanoparticles. Size, surface chemistry and shape are
      key nanocarrier properties to evaluate. Here, we have reviewed the most recent
      advances of NCDs in drug delivery systems, compared their behaviour with non
      dendritic stabilized nanoparticles and highlighted their challenges and promising
      applications in the future. 

PMID- 25566990
TI  - Stabilizing volatile liquid chemicals using co-crystallization.
AB  - A convenient, effective, and scalable protocol for stabilizing volatile liquid
      chemicals is reported. Through the use of halogen-bond driven co-crystal
      synthesis, several examples of liquid iodoperfluoroalkanes are transformed into
      crystalline materials with low-vapor pressure, considerable thermal stability,
      and moisture resistance. The target compounds can subsequently be re-generated
      through simple solvent-extractions. 

PMID- 25566988
TI  - Assessing the social vulnerability to malaria in Rwanda.
AB  - BACKGROUND: Since 2004, malaria interventions in Rwanda have resulted in
      substantial decline of malaria incidence. However, this achievement is fragile as
      potentials for local malaria transmissions remain. The risk of getting malaria
      infection is partially explained by social conditions of vulnerable populations.
      Since vulnerability to malaria is both influenced by social and environmental
      factors, its complexity cannot be measured by a single value. The aim of this
      paper is, therefore, to apply a composite indicator approach for assessing social
      vulnerability to malaria in Rwanda. This assessment informs the decision-makers
      in targeting malaria interventions and allocating limited resources to reduce
      malaria burden in Rwanda. METHODS: A literature review was used to conceptualize
      the social vulnerability to malaria and to select the appropriate vulnerability
      indicators. Indicators used in the index creation were classified into
      susceptibility and lack of resilience vulnerability domains. The main steps
      followed include selection of indicators and datasets, imputation of missing
      values, descriptive statistics, normalization and weighting of indicators, local
      sensitivity analysis and indicators aggregation. Correlation analysis helped to
      empirically evidence the association between the indicators and malaria
      incidence. RESULTS: The high values of social vulnerability to malaria are found
      in Gicumbi, Rusizi, Nyaruguru and Gisagara, and low values in Muhanga,
      Nyarugenge, Kicukiro and Nyanza. The most influential susceptibility indicators
      to increase malaria are population change (r = 0.729), average number of persons
      per bedroom (r = 0.531), number of households affected by droughts and famines (r
      = 0.591), and area used for irrigation (r = 0.611). The bed net ownership (r = 
      0.398) and poor housing wall materials (0.378) are the lack of resilience
      indicators that significantly correlate with malaria incidence. CONCLUSIONS: The
      developed composite index social vulnerability to malaria indicates which
      indicators need to be addressed and in which districts. The results from this
      study are salient for public health policy- and decision makers in malaria
      control in Rwanda and timely support the national integrated malaria initiative.
      Future research development should focus on spatial explicit vulnerability
      assessment by combining environmental and social drivers to achieve an integrated
      and complete assessment of vulnerability to malaria.

PMID- 25566987
TI  - Interactions between household air pollution and GWAS-identified lung cancer
      susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA).
AB  - We previously carried out a multi-stage genome-wide association study (GWAS) on
      lung cancer among never smokers in the Female Lung Cancer Consortium in Asia
      (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci
      at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at
      5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning
      for heating and cooking, is the leading cause of the overall disease burden in
      Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene
      HAP interactions associated with lung cancer in loci independent of smoking, we
      analyzed data from studies participating in FLCCA with fuel use information
      available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a
      30% increased risk of lung cancer (OR 1.3, 95% CI 1.0-1.6). Among the five a
      priori SNPs identified by our GWAS, two showed a significant interaction with
      coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p =
      0.04). The risk of lung cancer associated with coal exposure varied with the
      respective alleles for these two SNPs. Our observations provide evidence that
      genetic variation in HLA Class II and TP63 may modify the association between HAP
      and lung cancer risk. The roles played in the cell cycle and inflammation
      pathways by the proteins encoded by these two genes provide biological
      plausibility for these interactions; however, additional replication studies are
      needed in other non-smoking populations.

PMID- 25566991
TI  - CD44 regulates pancreatic cancer invasion through MT1-MMP.
AB  - Pancreatic cancer is one of the deadliest human malignancies due to its early
      metastatic spread and resistance to therapy. The mechanisms regulating pancreatic
      cancer metastasis are so far poorly understood. Here, using both in vitro and in
      vivo approaches, it is demonstrated that CD44, a transmembrane glycoprotein
      expressed on a subset of pancreatic cancer cells, is required for the induction
      of epithelial-mesenchymal transition (EMT) and the activation of an invasive
      program in pancreatic cancer. Mechanistically, the transcription factor Snail1
      (SNAI1), a regulator of the EMT program, is a downstream target of CD44 in
      primary pancreatic cancer cells and regulates membrane bound metalloproteinase
      (MMP14/MT1-MMP) expression. In turn, MT1-MMP expression is required for
      pancreatic cancer invasion. Thus, these data establish the CD44-Snail-MMP axis as
      a key regulator of the EMT program and of invasion in pancreatic cancer.
      IMPLICATIONS: This study sets the stage for CD44 and MT1-MMP as therapeutic
      targets in pancreatic cancer, for which small molecule or biologic inhibitors are
      available. Visual Overview:
      http://mcr.aacrjournals.org/content/early/2014/09/10/1541-7786.MCR-14
      0076/F1.large.jpg.

PMID- 25566992
TI  - EMT Transition Alters Interstitial Fluid Flow-Induced Signaling in ERBB2-Positive
      Breast Cancer Cells.
AB  - A variety of biophysical forces are altered in the tumor microenvironment (TME)
      and these forces can influence cancer progression. One such force is interstitial
      fluid flow (IFF)-the movement of fluid through the tissue matrix. IFF was
      previously shown to induce invasion of cancer cells, but the activated signaling
      cascades remain poorly understood. Here, it is demonstrated that IFF induces
      invasion of ERBB2/HER2-expressing breast cancer cells via activation of
      phosphoinositide-3-kinase (PI3K). In constitutively activate ERBB2-expressing
      cells that have undergone epithelial-to-mesenchymal transition (EMT), IFF
      mediated invasion requires the chemokine receptor CXCR4, a gradient of its ligand
      CXCL12, and activity of the PI3K catalytic subunits p110alpha and beta. In wild
      type ERBB2-expressing cells, IFF-mediated invasion is chemokine receptor
      independent and requires only p110alpha activation. To test whether cells
      undergoing EMT alter their signaling response to IFF, TGFbeta1 was used to induce
      EMT in wild-type ERBB2-expressing cells, resulting in IFF-induced invasion
      dependent on CXCR4 and p110beta. IMPLICATIONS: This study identifies a novel
      signaling mechanism for interstitial flow-induced invasion of ERBB2-expressing
      breast cancer cells, one that depends on EMT and acts through a CXCR4-PI3K
      pathway. These findings suggest that the response of cancer cells to interstitial
      flow depends on EMT status and malignancy.

PMID- 25566993
TI  - The Ras-Membrane Interface: Isoform-specific Differences in The Catalytic Domain.
AB  - The small GTPase Ras is mutated in about 20% of human cancers, primarily at
      active site amino acid residues G12, G13, and Q61. Thus, structural biology
      research has focused on the active site, impairment of GTP hydrolysis by
      oncogenic mutants, and characterization of protein-protein interactions in the
      effector lobe half of the protein. The C-terminal hypervariable region has
      increasingly gained attention due to its importance in H-Ras, N-Ras, and K-Ras
      differences in membrane association. A high-resolution molecular view of the Ras
      membrane interaction involving the allosteric lobe of the catalytic domain has
      lagged behind, although evidence suggests that it contributes to isoform
      specificity. The allosteric lobe has recently gained interest for harboring
      potential sites for more selective targeting of this elusive "undruggable"
      protein. The present review reveals critical insight that isoform-specific
      differences appear prominently at these potentially targetable sites and
      integrates these differences with knowledge of Ras plasma membrane localization,
      with the intent to better understand the structure-function relationships needed
      to design isoform-specific Ras inhibitors.

PMID- 25566995
TI  - Type 1 diabetes still shortens life span, Scottish study finds.

PMID- 25566994
TI  - A Controlled Health Promoting School Study in the Netherlands: Effects After 1
      and 2 Years of Intervention.
AB  - PURPOSE: Many unhealthy behavioral habits often originate in adolescence. In the
      literature, the school-based whole school approach is stated be the most
      promising way to promote healthy behavior. Herein, interventions are evidence
      based and integrated into the curriculum, while embedded in complementary healthy
      school policies and environment. This study evaluates the effects of such an
      intervention on Dutch high schools. METHODS: Two Dutch high schools and two
      controls were followed to evaluate the intervention's effects on health
      behaviors, body mass index, and psychosocial problems after 1 year (N = 969) and
      2 years (N = 605). Outcomes were measured via self-report surveys and analyzed
      with mixed methods regression analyses. To complement information on intervention
      effects, structured interviews were held with a representative sample of teachers
      per intervention school to map their respective whole school approach
      implementation success. RESULTS: After 2 years, one intervention school showed
      significant improvements: Body mass index and excessive screen time use were
      reduced. In the other intervention school, priority targets did not improve.
      These findings reflected their respective success in intervention implementation,
      for example, differences in intervention integration and tailoring. CONCLUSIONS:
      This study shows that it is feasible for schools to implement a comprehensive
      Health Promoting School intervention themselves and that, when successful,
      effects in terms of improving behaviors and health outcomes are promising. The
      process evaluation helped understand these findings in context.

PMID- 25566996
TI  - Are nurses more likely to report providing care plans for chronic disease
      patients than doctors? Findings from a New Zealand study.
AB  - OBJECTIVES: The main aim of this study was to compare the perceptions of general
      practitioners (GPs) and primary care nurses (PCNs) in the Southern Region of New
      Zealand regarding their provision of chronic illness care. Whether PCNs rated
      their frequency of providing aspects of chronic illness care higher than GPs was
      a key question. METHODS: The modified version of the Patient Assessment of
      Chronic Illness Care (PACIC) was used to compare the perceptions of GPs and PCNs.
      RESULTS: Surveys were received from 77% of practices in the Southern region.
      Responding PCNs were more likely than their GP counterparts to document they
      provided aspects of chronic illness care 'most of the time' or 'always' in 18
      activities from the six M-PACIC domains. Their level of providing patients with
      formal care plans was surprisingly low. CONCLUSION: This level of engagement of
      PCNs with chronic illness care was no surprise. The low number reporting they
      provided patients with a care plan, most of the time or always, was unexpected.
      Aspects of care planning, however, were reported as taking place more frequently.
      This discrepancy between the process of care planning and the outcome, a care
      plan, is not unique to this region of New Zealand and warrants further research.

PMID- 25566997
TI  - Friedreich's ataxia: the European consortium.

PMID- 25566999
TI  - Surveillance of catheter-related infections: the supplementary role of the
      microbiology laboratory.
AB  - BACKGROUND: The burden of catheter-related infections (CRIs) in developing
      countries is severe. In South Africa, a standardised surveillance definition does
      not exist and the collection of catheter days is challenging. The aim of the
      study was to provide baseline data on the prevalence of CRIs and to describe the
      epidemiology of CRI events within a tertiary academic hospital. METHODS:
      Surveillance was laboratory-based and conducted for a six month period. A
      microbiologically confirmed CRBSI (MC-CRBSI) event was defined as the isolation
      of the same microorganism from the catheter and concomitant blood cultures (BCs),
      within 48 h of catheter removal, which were not related to an infection at
      another site. RESULTS: A total of 508 catheters, removed from 332 patients, were
      processed by the laboratory, of which only 50% (253/508 removed from 143/332
      patients) of the catheters were accompanied by BCs within 48 h. Sixty-five
      episodes of MC-CRBSI in 57 patients were detected, involving 71 catheters and 195
      microbial isolates. The institutional prevalence rate was 3.7 episodes per 1 000
      admissions and 5.8 episodes per 10 000 in-patient days. Catheter day data was
      collected in only six wards of the hospital. The pooled laboratory incidence was
      10.1 MC-CRBSI episodes per 1 000 catheter days, whereas the hospital-based
      central line-associated bloodstream infection (CLABSI) rate was pooled at 5.7
      episodes per 1 000 catheter days. The majority of patients had an underlying
      gastro-intestinal condition (33%; 19/56) with a non-tunnelled, triple-lumen
      central venous catheter, placed in the subclavian vein (38%; 27/71). The most
      predominant pathogen was methicillin-resistant Staphylococcus epidermidis (28%;
      55/195), followed by extensively-drug resistant Acinetobacter baumannii (18%;
      35/195). CONCLUSIONS: Catheter-related infection prevention and control efforts
      require urgent attention, not only to keep patients safe from preventable harm,
      but to prevent the spread of multidrug resistant microorganisms.

PMID- 25567000
TI  - Tubular carcinoma of the breast: institutional and SEER database analysis
      supporting a unique classification.
AB  - BACKGROUND: Tubular carcinoma (TC) of the breast is an uncommon, well
      differentiated subtype of breast cancer with an excellent prognosis, but
      ambiguity in how it should be defined and treated. OBJECTIVE: To determine the
      clinicopathologic characteristics and survival outcomes of patients with TC.
      METHODS: The University of Virginia (UVA) Breast Cancer Database and the
      Surveillance, Epidemiology and End Results (SEER) databases were queried for
      patients with either grade 1 TC or grade 1 ductal (G1D) breast cancer. RESULTS:
      Nineteen institutional TC cases were identified and compared to 54 G1D cases.
      Flat epithelial atypia frequently was found with TC and not with G1D. There was
      no difference in overall or progression free survival. In SEER 18, 9,565 cases of
      TC were found. Most cases were stage I and patient characteristics were nearly
      identical. Both cause specific survival and overall survival were significantly
      longer for TC when compared to G1D. CONCLUSIONS: This review shows TC to have
      favorable behavior, with similar features to, but superior survival compared to
      low-grade ductal carcinoma of the breast. This suggests the adequacy of
      histopathologic review while reinforcing the designation of TC as a unique
      subtype.

PMID- 25566998
TI  - Biological and clinical characteristics of the European Friedreich's Ataxia
      Consortium for Translational Studies (EFACTS) cohort: a cross-sectional analysis
      of baseline data.
AB  - BACKGROUND: Friedreich's ataxia is a rare autosomal recessive neurodegenerative
      disorder. Here we report cross-sectional baseline data to establish the
      biological and clinical characteristics for a prospective, international,
      European Friedreich's ataxia database registry. METHODS: Within the European
      Friedreich's Ataxia Consortium for Translational Studies (EFACTS) framework, we
      assessed a cohort of patients with genetically confirmed Friedreich's ataxia. The
      primary outcome measure was the Scale for the Assessment and Rating of Ataxia
      (SARA) and secondary outcome measures were the Inventory of Non-Ataxia Signs
      (INAS), the performance-based coordination test Spinocerebellar Ataxia Functional
      Index (SCAFI), the neurocognitive phonemic verbal fluency test, and two quality
      of-life measures: the activities of daily living (ADL) part of the Friedreich's
      Ataxia Rating Scale and EQ-5D. The Friedreich's ataxia cohort was subdivided into
      three groups: early disease onset (<=14 years), intermediate onset (15-24 years),
      and late onset (>=25 years), which were compared for clinical characteristics and
      outcome measures. We used linear regression analysis to estimate the annual
      decline of clinical outcome measures based on disease duration. This study is
      registered with ClinicalTrials.gov, number NCT02069509. FINDINGS: We enrolled 592
      patients with genetically confirmed Friedreich's ataxia between Sept 15, 2010,
      and April 30, 2013, at 11 sites in seven European countries. Age of disease onset
      was inversely correlated with the number of GAA repeats in the frataxin (FXN)
      gene: every 100 GAA repeats on the smaller repeat allele was associated with a
      2.3 year (SE 0.2) earlier onset. Regression analyses showed significant estimated
      annual worsening of SARA (regression coefficient 0.86 points [SE 0.05], INAS
      (0.14 points [0.01]), SCAFI Z scores (-0.09 [0.01]), verbal fluency (-0.34 words
      [0.07]), and ADL (0.64 points [0.04]) during the first 25 years of disease; the
      regression slope for health-related quality-of-life state from EQ-5D was not
      significant (-0.33 points [0.18]). For SARA, the predicted annual rate of
      worsening was significantly higher in early-onset patients (n=354; 1.04 points
      [0.13]) and intermediate-onset patients (n=137; 1.17 points [0.22]) than in late
      onset patients (n=100; 0.56 points [0.10]). INTERPRETATION: The results of this
      cross-sectional baseline analysis of the EFACTS cohort suggest that earlier
      disease onset is associated with larger numbers of GAA repeats and more rapid
      disease progression. The differential estimated progression of ataxia symptoms
      related to age of onset have implications for the design of clinical trials in
      Friedreich's ataxia, for which SARA might be the most suitable measure to monitor
      disease progression. FUNDING: European Commission.

PMID- 25567002
TI  - Sex work and the claim for grassroots legislation.
AB  - The aim of this paper is to contribute to understanding of legal models that aim
      to control sex work, and the policy implications of these, by discussing the
      experience of developing a grassroots legislation bill proposal by organised sex
      workers in Cordoba, Argentina. The term 'grassroots legislation' here refers to a
      legal response that derives from the active involvement of local social movements
      and thus incorporates the experiential knowledge and claims of these particular
      social groupings in the proposal. The experience described in this paper excludes
      approaches that render sex workers as passive victims or as deviant perpetrators;
      instead, it conceives of sex workers in terms of their political subjectivity and
      of political subjectivity in its capacity to speak, to decide, to act and to
      propose. This means challenging current patterns of knowledge/power that give
      superiority to 'expert knowledge' above and beyond the claims, experiences,
      knowledge and needs of sex workers themselves as meaningful sources for law
      making. 

PMID- 25567001
TI  - Diagnosis of secondary amyloidosis in alkaptonuria.
AB  - BACKGROUND: Alkaptonuria (AKU) is an inborn error of catabolism due to a
      deficient activity of homogentisate 1,2-dioxygenase. Patients suffer from a
      severe arthropathy, cardiovascular and kidney disease but other organs are
      affected, too. We found secondary amyloidosis as a life-threatening complication
      in AKU, thus opening new perspectives for its treatment. We proved that
      methotrexate and anti-oxidants have an excellent efficacy to inhibit the
      production of amyloid in AKU model chondrocytes. Owing to the progressive and
      intractable condition, it seems important to detect amyloid deposits at an early
      phase in AKU and the choice of specimens for a correct diagnosis is crucial.
      METHODS: Ten AKU subjects were examined for amyloidosis; abdominal fat pad
      aspirates, labial salivary gland, cartilage and synovia specimens were analysed
      by CR, Th-T, IF, TEM. RESULTS: Amyloid was detected in only one abdominal fat pad
      specimen. However, all subjects demonstrated amyloid deposition in salivary
      glands and in other organ biopsies, indicating salivary gland as the ideal
      specimen for early amyloid detection in AKU. CONCLUSIONS: This is, at the best of
      our knowledge, the first report providing correct indications on the diagnosis of
      amyloidosis in AKU, thus offering the possibility of treatment of such co
      morbidity to AKU patients. VIRTUAL SLIDES: The virtual slide(s) for this article
      can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_185.

PMID- 25567003
TI  - The use of positron emission tomography/computed tomography imaging in radiation
      therapy: a phantom study for setting internal target volume of biological target
      volume.
AB  - BACKGROUND: Fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed
      tomography (PET/CT) is an important method for detecting tumours, planning
      radiotherapy treatment, and evaluating treatment responses. However, using the
      standardized uptake value (SUV) threshold with PET imaging may be suitable not to
      determine gross tumour volume but to determine biological target volume (BTV).
      The aim of this study was to extract internal target volume of BTV from PET
      images. METHODS: Three spherical densities of (18)F-FDG were employed in a
      phantom with an air or water background with repetitive motion amplitudes of 0-30
      mm. The PET data were reconstructed with attenuation correction (AC) based on CT
      images obtained by slow CT scanning (SCS) or helical CT scanning (HCS). The
      errors in measured SUVmax and volumes calculated using SUV threshold values based
      on SUVmax (THmax) in experiments performed with varying extents of respiratory
      motion and AC were analysed. RESULTS: A partial volume effect (PVE) was not
      observed in spheres with diameters of >= 28 mm. When calculating SUVmax and
      THmax, using SCS for AC yielded smaller variance than using HCS (p<0.05). For
      spheres of 37- and 28-mm diameters in the phantom with either an air or water
      background, significant differences were observed when mean THmax of 30-, 20-, or
      10-mm amplitude were compared with the stationary conditions (p<0.05). The
      average THmax values for 37-mm and 28-mm spheres with an air background were
      0.362 and 0.352 in non-motion, respectively, and the mean THmax values for 37-mm
      and 28-mm spheres with a water background were 0.404 and 0.387 in non-motion and
      0.244 and 0.263 in motion, respectively. When the phantom background was air,
      regardless of sphere concentration or size, THmax was dependent only on motion
      amplitude. CONCLUSIONS: We found that there was no PVE for spheres with >= 28-mm
      diameters, and differences between SUVmax and THmax were reduced by using SCS for
      AC. In the head-and-neck and the abdomen, the standard values of THmax were 0.25
      and 0.40 with and without respiratory movement, respectively. In the lungs, the
      value of THmax became the approximate expression depending on motion amplitude.

PMID- 25567005
TI  - Luminescence signature of free exciton dissociation and liberated electron
      transfer across the junction of graphene/GaN hybrid structure.
AB  - Large-area graphene grown on Cu foil with chemical vapor deposition was
      transferred onto intentionally undoped GaN epilayer to form a graphene/GaN
      Schottky junction. Optical spectroscopic techniques including steady-state and
      time-resolved photoluminescence (PL) were employed to investigate the electron
      transfer between graphene and n-type GaN at different temperatures. By comparing
      the near-band-edge excitonic emissions before and after the graphene covering,
      some structures in the excitonic PL spectra are found to show interesting
      changes. In particular, a distinct "dip" structure is found to develop at the
      center of the free exciton emission peak as the temperature goes up. A mechanism
      that the first dissociation of some freely moveable excitons at the interface was
      followed by transfer of liberated electrons over the junction barrier is proposed
      to interpret the appearance and development of the "dip" structure. The formation
      and evolution process of this "dip" structure can be well resolved from the
      measured time-resolved PL spectra. First-principles simulations provide clear
      evidence of finite electron transfer at the interface between graphene and GaN. 

PMID- 25567004
TI  - Characterization and immunological activity of different forms of recombinant
      secreted Hc of botulinum neurotoxin serotype B products expressed in yeast.
AB  - The recombinant Hc proteins of botulinum neurotoxins and tetanus toxin are
      exclusively produced by intracellular heterologous expression in Pichia pastoris
      for use in subunit vaccines; the same Hc proteins produced by secreted
      heterologous expression are hyper-glycosylated and immunologically inert. Here,
      several different recombinant secreted Hc proteins of botulinum neurotoxin
      serotype B (BHc) were expressed in yeast and we characterized and assessed their
      immunological activity in detail. Recombinant low-glycosylated secreted BHc
      products (BSK) were also immunologically inert, similar to hyper-glycosylated BHc
      products (BSG), although deglycosylation restored their immunological activities.
      Unexpectedly, deglycosylated proBHc contained an unexpected pro-peptide of an
      alpha-factor signal and fortuitous N-linked glycosylation sites in the non
      cleaved pro-peptide sequences, but not in the BHc sequences. Notably, a non
      glycosylated secreted homogeneous BHc isoform (mBHc), which we successfully
      prepared after deleting the pro-peptide and removing its single potential
      glycosylation site, was immunologically active and could confer effective
      protective immunity, similarly to non-glycosylated rBHc. In summary, we conclude
      that a non-glycosylated secreted BHc isoform can be prepared in yeast by deleting
      the pro-peptide of the alpha-factor signal and mutating its single potential
      glycosylation site. This approach provides a rational and feasible strategy for
      the secretory expression of botulism or other toxin antigens. 

PMID- 25567006
TI  - Low-dose computed tomography in the evaluation of urolithiasis.

PMID- 25567008
TI  - [Dominance analysis on the association between reasons for smoking and results
      related to successful smoking cessation].
AB  - OBJECTIVE: To study the association between reasons for smoking and results
      related to successful smoking cessation. METHODS: A community-based case-control
      study was conducted with 642 male adults recognized as successful spontaneous
      smoking quitters being the subject cases while another 700 male adults who had
      failed to quit smoking were served as the controls. Russell Reason for Smoking
      Questionnaire (RRSQ) was used to investigate the reasons for smoking. Dominance
      logistic regression was performed to determine the relative importance of reasons
      for starting smoking and the endpoint of successful quit smoking. RESULTS: After
      adjusting the potential confounders of age, age of smoking initiation, marital
      status, profession, and education, the adjusted means of sedative and stimulation
      of RRSQ in the successful quitters were significant lower than that in the failed
      quitters. Results from the dominance logistic regression showed that the first
      two important factors for smoking cessation were sedative and stimulation of
      RRSQ, followed by psychological image, automatic, hand-mouth activity,
      indulgence, and addiction. CONCLUSION: This study demonstrated that factors as
      dependence-addiction showed more important impacts than the social-psychological
      ones on the endpoint of successful smoking cessation.

PMID- 25567007
TI  - Control of microtubule trajectory within an electric field by altering surface
      charge density.
AB  - One of challenges for using microtubules (MTs) driven by kinesin motors in
      microfluidic environments is to control their direction of movement. Although
      applying physical biases to rectify MTs is prevalent, it has not been established
      as a design methodology in conjunction with microfluidic devices. In the future,
      the methodology is expected to achieve functional motor-driven nanosystems. Here,
      we propose a method to guide kinesin-propelled MTs in multiple directions under
      an electric field by designing a charged surface of MT minus ends labeled with
      dsDNA via a streptavidin-biotin interaction. MTs labeled with 20-bp or 50-bp
      dsDNA molecules showed significantly different trajectories according to the DNA
      length, which were in good agreement with values predicted from electrophoretic
      mobilities measured for their minus ends. Since the effective charge of labeled
      DNA molecules was equal to that of freely dispersed DNA molecules in a buffer
      solution, MT trajectory could be estimated by selecting labeling molecules with
      known charges. Moreover, the estimated trajectory enables to define geometrical
      sizes of a microfluidic device. This rational molecular design and prediction
      methodology allows MTs to be guided in multiple directions, demonstrating the
      feasibility of using molecular sorters driven by motor proteins. 

PMID- 25567009
TI  - [Using the revised Chinese diet balance index Quality of Diet to evaluate the
      quality of diet among rural residents in Hanzhong, Shaanxi province and relative
      influencing factors].
AB  - OBJECTIVE: To evaluate the quality of diet among rural residents in Hanzhong,
      Shaanxi province and to investigate the relative factors. METHODS: A cross
      sectional survey on dietary status together with a semi-quantitative food
      frequency questionnaire were conducted among rural residents aged between 18 and
      80 in Hanzhong of Shaanxi, in 2010. Quality of diet was evaluated by using DBI-07
      scoring and evaluating system. Linear regression models were developed to
      identify factors related to under or over intakes. RESULTS: 2 241 rural residents
      were under study. 65% of the residents' daily intake of grains, oil and salt
      exceeded the RNI while animal food, diary food, eggs, vegetables and fruits were
      under, to some extent. The average values of DBI_LBS and DBI_HBS were 24.83 and
      5.70. The proportions of moderate under-intake (25<=DBI_LBS<=36) and moderate
      over-intake (14<=DBI_HBS<=19)were 33.4% and 51.0%. Factors as family number,
      education level, fortune index, physical activity, higher labor intensity seemed
      to be protective for dietary under intake (P < 0.05). Moderate fortune index,
      drinking alcohol (more than once a week), being male, age and smoking status(>15
      cigarettes per day)were risk factors for over-intake of diet (P < 0.05). Factors
      as larger family size and having had education above the levels senior school
      were significantly and negatively associated with the over-intake of diet (P <
      0.05). CONCLUSION: The main diet problem among the rural residents was related to
      under-intaken but over-intake did exist to some extents. Our study results called
      for specific intervention in improving the quality of diet among the residents in
      Hanzhong.

PMID- 25567010
TI  - [Matching study on immune response between single anti-HBc positivity and healthy
      adults after primary immunization and revaccination of hepatitis B vaccine].
AB  - OBJECTIVE: To compare the antibody response between adults with hepatitis B virus
      (HBV) core antibody (anti-HBc) single positivity and healthy adults after primary
      immunization and revaccination of hepatitis B vaccine(HepB). METHODS: Adults aged
      from 18 to 49 who were both negative for HBV surface antigen (HBsAg) and antibody
      to HBsAg (anti-HBs), but positive for anti-HBc and narrated no history of HepB
      immunization by themselves, were selected as single anti-HBc positive group
      ('anti-HBc alone'). Adults who were negative for HBsAg, anti-HBs and anti-HBc,
      with age differences within 2 years, and same gender under the 1 : 1 matching
      program, were selected to form the control group. Both groups were vaccinated on
      0-1-6 schedule with the same HepB. Those who were non-response to HepB at primary
      immunization were revaccination on 0-1-6 schedule. Response rates and geometric
      mean concentrations (GMC) between the two groups were compared. RESULTS: In
      total, the number of anticipants were 228 pairs. Rates on non-response, low
      response, normal-response and high-response after the primary immunization were
      8.77% , 11.84%, 31.14% and 48.25% in the control group respectively. The
      corresponding rates were 8.33%, 30.70%, 35.96% and 25.00% in the 'anti-HBc
      alone'. The rate of low-response in the control group was lower than that in the
      'anti-HBc alone' (chi(2) = 22.28, P < 0.01), while the rate of high-response was
      higher than that in the control group (chi(2) = 24.43, P < 0.01). GMC of anti-HBs
      in the control group (534.07 mIU/ml) was higher than that in the 'anti-HBc alone'
      (183.99 mIU/ml) (u = 4.42, P < 0.01). The anti-HBs conversion rates were 82.35%
      and 41.18% in the control group and in the 'anti-HBc alone' respectively after
      the first-dose revaccination, but increased to 90.00% and 82.35% after the third
      dose revaccination. The anti-HBs conversion rates in the control group were
      higher than that in the 'anti-HBc alone' after the first-dose revaccination (P <
      0.05), while there was no difference seen between the two groups after the third
      dose revaccination (P > 0.05). CONCLUSION: Immune response in the anti-HBc
      positive adults after primary immunization was weaker than that in common adults.
      However, immune response induced by HepB was enough to prevent them from
      infecting HBV. The rates of response showed an obvious increase after
      revaccination, hence the same HepB immunization strategy could be used.

PMID- 25567011
TI  - [Study on the risk factors of measles among the 8-month-olds and children>=15
      years of age in Gansu province].
AB  - OBJECTIVE: To understand the risk factors of measles among babies under 8-months
      old and people >=15 years old, in Gansu province. METHODS: Laboratory-confirmed
      measles cases were divided into two groups among children below 8-months-old and
      those >=15 year olds. Descriptive epidemiology and 1:3 case control study were
      conducted to find out those related risk factors as:hospital exposure, contact
      with measles cases, vaccination, history of measles etc. so as to determine the
      risk factors and appropriate control measures. RESULTS: Histories of hospital
      exposure, contact with measles cases and travelling to other cities were risk
      factors for measles among babies younger than 8-months and people >=15 year olds.
      Vaccination appeared a protective factor for people >=15 years of age. From 42
      cases and 126 controls, through multivariate analysis, results showed that
      hospital exposure was the only significant factor ( OR = 29.23, 95%CI:2.82
      302.89)for those babies younger than 8-months. Factors as hospital exposure and
      travelling among cities for 7-21 days before being infected, were with
      significant importance ( OR = 5.15, 95% CI:2.28-11.63; OR = 5.48, 95%CI:1.38
      21.69)for people >=15 years of age, according to the observation from 74 cases
      and 222 controls. CONCLUSION: In order to reduce the incidence of measles among
      babies under 8-month-old and people >=15 years old, efforts on control of
      nosocomial infection should be strengthened, while the routine immunization
      coverage need to be increased for the children at higher risks, to reduce the
      source of infection.

PMID- 25567012
TI  - [Study on the prevalence and associated risk factors related to HIV, syphilis,
      herpes simplex virus-2 among female sex workers in Jiaozhou, Shandong province].
AB  - OBJECTIVE: To analyze the prevalence rates and associated risk factors on HIV,
      syphilis, herpes simplex virus-2 (HSV-2) among female sex workers (FSWs) in
      Jiaozhou, Shandong province. METHODS: Through convenient sampling, an anonymous
      questionnaire survey was conducted on female sex workers to collect related
      information. Blood specimens were drawn for serological tests on HIV, syphilis
      and HSV-2 antibodies, respectively. Patients with positive results from both
      treponema pallidum and HSV-2 tested by ELISA method, were defined as being
      superinfected. RESULTS: A total of 460 FSWs were recruited in this study. The
      prevalence rates of HIV, syphilis, HSV-2, and syphilis/HSV-2 superinfection were
      0.22% , 5.9% , 43.0% , and 11.7% , respectively. Among the methamphetamine users,
      the prevalence rates of syphilis, HSV-2, and syphilis/HSV-2 superinfection were
      12.4%, 55.2%, and 22.9%, respectively. Results from multivariate analysis showed
      that factors that significantly associated with syphilis infection would include:
      methamphetamine use (OR = 3.61, 95% CI:1.62-8.06), having first commercial sex
      intercourse at under 20 years of age (OR = 2.80, 95% CI:1.15-6.85), more than 2
      establishments that the FSWs worked in the last month (OR = 4.37, 95%CI:0.83
      22.83). Factors associated with HSV-2 infection were methamphetamine use (OR =
      2.30, 95%CI:1.43-3.70), having first commercial sex intercourse at under 20 years
      of age (OR = 1.77, 95% CI:1.16-2.69), working at low-end establishments (OR =
      2.61, 95%CI:1.66-4.10), working at the local sex-work venues for more than one
      year (OR = 2.01, 95% CI:1.28-3.14), with low education backgrounds (OR = 2.27,
      95% CI:1.18-4.36), using methamphetamine (OR = 3.95, 95% CI:2.09-7.44), low
      education background (OR = 2.43, 95% CI: 1.10-5.36), 21-30 year-olds (OR = 2.95,
      95%CI:1.08-8.03), older than 31 years of age (OR = 7.05, 95% CI:2.48-20.01) etc.,
      were independent risk factors associated with the superinfection of syphilis and
      HSV-2. CONCLUSION: The prevalence rates of syphilis, HSV-2 and syphilis/HSV-2
      superinfection were relatively high among FSWs in Jiaozhou, especially among the
      FSWs who were methamphetamine users.

PMID- 25567013
TI  - [Study on of the current status of volatile organic compounds pollution in
      typical rural drinking water and the relationship between its concentration and
      health of the population, in Huai'an, Jiangsu].
AB  - OBJECTIVE: This study was to understand the status of pollution on drinking
      water, by volatile organic compounds (VOCs), among rural residents living in the
      basin of Huaihe River. Relationship between the morbidity, morbidity of cancers
      and VOCs were also explored. METHODS: 28 villages were chosen from Xuyi,Jinhu,
      Chuzhou along the Huaihe River, with water samples collected from ditch pond
      water, shallow wells, deep wells in November-December 2010. VOCs indicators were
      evaluated according to the Standard Quality GB 5749-2006 for Drinking Water.
      RESULTS: Methylene chloride, chloroform, benzene and carbon tetrachloride were
      all detected in 76 water samples. The rates of chloroform, benzene, carbon
      tetrachloride which exceeding the quality standards were 3.95% , 21.05% and
      22.37% , but no significant differences were found among these three water
      resources in chloroform, benzene or carbon tetrachloride. Results from the
      correlation analysis showed that benzene had positive correlation with tumor
      deaths (r = 0.24, P < 0.05). Results from the risk assessment on health showed
      that some chloroform, benzene, carbon tetrachloride products which were related
      to the risks of cancers were exceeding the acceptable ranges of risk, with the
      rates as 28.95%, 22.37% and 64.47% but with no significant differences among the
      three water resources (P > 0.05). CONCLUSION: Drinking waters for rural residents
      along the Huaihe River were polluted while VOCs might have related to tumor
      incidence with potential impact and risk to the health of local residents.

PMID- 25567014
TI  - [A cohort study on the characteristics of the recurrent epidemics on hand, foot
      and mouth disease, in Fujian province].
AB  - OBJECTIVE: To explore the recurrent epidemiological characteristics of hand, foot
      and mouth disease (HFMD) among children aged <4 years to provide evidence for
      HFMD prevention and control. METHODS: Principles on historical cohort study were
      followed when analyzing data related to HFMD surveillance in Fujian province. All
      the research objects were restricted to patients aged <4, with HFMD and who were
      permanent residents in Fujian province. Characteristics of the study objects were
      extracted as potential factors when the patients first showed symptoms of HFMD.
      These factors might cause the recurrence of HFMD and were filtered by the
      logistic stepwise regression with SAS 9.0. RESULTS: A total of 82 949 children
      were included. Among them, 2 612 had repetitiously suffered from HFMD(occupied
      3.15%), including 2 510 who had the histories of suffering twice, 98 suffering
      three times, 3 suffering four times, and 1 even suffering five times. Comparing
      with the objects who had the first onset at the age of 3, also with the risk
      increased to 4.39 (95%CI:3.80-5.07) times, when compared to those who had the
      first onset at the age below 2. Again, the risk among children whose first onset
      was at the age of 2 had increased to 2.73 (95% CI: 2.35-3.18) times. According to
      the current residents areas, the morbidities of patients under 6 years old were
      below 2% when the symptoms first started, but the risk of the objects whose
      morbidities were higher than 4% , had increased 2.15(95% CI:1.88-2.45)times.
      Again, risk of the objects whose morbidities were between 3% and 4% had increased
      to 2.10 (95%CI:1.85-2.38) times. Among those whose specific morbidities were
      between 2% and 3% , the risk had increased to 1.65 (95% CI: 1.44-1.89) times.
      Comparing with the objects who never visited any maternal/child care settings
      when started the first onset, the risk among the ones who had been to the
      maternal/child care settings, had increased to 1.64 (95% CI:1.51-1.78) times.
      Boys had the risk 1.34 (95% CI:1.23-1.46)times increase than girls. The
      preponderant pathogen causing HFMD recurrence was EV71 (33/60). Recurrence might
      cause more severe symptoms or signs (8/2 612). Pathogens causing the initial
      infection and recurrence might both belonged to the same-EV71 (3/6). CONCLUSION:
      Recurrence of the disease were closely related to the opportunities of contacting
      the pathogens. Interventions should be imposed on patients in time as soon as the
      disease initiated, especially at the younger age.

PMID- 25567015
TI  - [Recent infected and newly reported HIV cases in Jiangsu province, 2011-2013].
AB  - OBJECTIVE: To understand the status of recent infected and newly reported HIV
      cases in Jiangsu province. METHODS: Information including general demographic,
      mode of transmission and sample source of newly reported HIV infected cases was
      collected. Corresponding serum or plasma samples were collected and tested with
      BED-CEIA. Proportions of recent HIV infections among different populations were
      calculated, and associated factors of recent HIV infection calculated. RESULTS:
      Among cases infected through different channels as homosexual, heterosexual and
      needles sharing, the proportions of recent infections were 29.19% , 17.40% and
      21.75% , respectively. Statistically significant difference was seen between
      different populations(P < 0.05). Compared with female cases, male cases were more
      likely to be recent infected (OR = 1.569, 95%CI: 1.168-2.107). Compared with
      cases older than 35 years of age, the ones that younger than that age were more
      likely to be recently infected (OR = 1.556, 95% CI:1.289-1.879). Compared with
      cases who remained single, those married cases were more likely to be long-term
      infections(OR = 0.789, 95%CI:0.649-0.960). Compared with patients identified by
      hospitals, the recent HIV infections were more likely to be found through
      voluntary counseling programs and testing (OR = 2.278, 95%CI: 1.853-2.801),
      project-based surveillance programs (OR = 2.409, 95%CI:1.860- 3.120), and unpaid
      blood donation sites (OR = 2.911, 95%CI:2.118-4.001)(P < 0.05). CONCLUSION:
      Proportion of MSM ranked 1st in the newly reported HIV cases in Jiangsu province.
      Related HIV case-finding programs should be strengthened to reduce the secondary
      transmission.

PMID- 25567016
TI  - [Epidemiological characteristics of HCV infected children under 15 years of age,
      in Henan province from 2008 to 2013].
AB  - OBJECTIVE: To describe the epidemiological characteristics and changing trend of
      HCV-related children in Henan province. METHODS: Data was analyzed based on the
      case-reporting records on hepatitis C from 2008 to 2013. RESULTS: The number of
      reported cases and incidence of HCV-related children had increased annually from
      2008 to 2012. The reported incidence on HCV-related children increased from 2.37
      per 100 000 in 2008, to 3.23 per 100 000 in 2012, but it decreased to 1.77 per
      100 000 in 2013. Reported cases on females increased annually. The 0-1 age group
      had the largest proportion but it decreased annually. Large cities as Zhengzhou,
      had high incidence, and the mobile population within the province also showed an
      annual increase, from 49.02% in 2008, to 59.77% in 2013. Time between onset and
      diagnosis(days) of the disease increased and the M and IQR from 2008 to 2013
      appeared as 0(0-2), 0(0-2), 1(0-2), 1(0-3), 1(0-5) and 1(0-3). CONCLUSION: The
      incidence of HCV-related children in Henan province showed an annual increase,
      along with the increasing trend of mobile population in the province as well as
      the longer time span between onset and diagnosis of the disease. It is suggested
      that strengthening the program on monitor, as well as on effective prevention and
      control measures be in place accordingly. Targets should also be focused on
      pregnant women, migrants, other key groups, so as to better perform on early
      detection and treatment.

PMID- 25567017
TI  - [Study on the genotype and epidemic characteristics of diarrheagenic Escherichia
      coli isolated from diarrheal patients in Beijing].
AB  - OBJECTIVE: To understand the distribution of virulence gene and the
      epidemiological characteristics of diarrheagenic Escherichia(E.) coli (DEC) from
      diarrheal patients in Beijing. METHODS: Stool specimens from diarrheal patients
      were cultured which were collected from the hospitals under sentinel surveillance
      program, during 2012-2013. DNA was examined by real-time PCR. RESULTS: 253 out of
      6 370 specimens were positive for DEC detection with the rate as 4.0%. A total
      number of 262 DEC strains were isolated. Two different pathotypes of DEC strains
      with mixed infection, were isolated from 9 specimens. Different pathotypes would
      show the following profiles: 42.8% for enteropathogenic E. coli (EPEC) including
      42.0% atypical and 0.8% typical; 38.9% for enterotoxigenic E. coli (ETEC)
      including 24.8% st positive, 9.9% lt positive and 4.2% st and lt both
      positive;15.3% for enteroaggregative E. coli(EAEC);2.7% for enteroinvasive E.
      coli (EIEC); one strain STEC with serotype O26:K60. ETEC had obvious
      characteristics on age. All kinds of DEC were isolated throughout the year with
      seasonal fluctuation. CONCLUSION: DEC isolates from diarrheal patients in Beijing
      were dominated by EPEC and ETEC, with atypical ones accounted for the majority of
      EPEC. One specimen was found under mixed infection. Pathotypes DEC were found to
      have different age and seasonal distributions.

PMID- 25567018
TI  - [Evaluation on the hepatitis A vaccine in preventing hepatitis A infection in
      Tianjin, from 2000 to 2011].
AB  - OBJECTIVE: Hepatitis A immunization strategies were carried out in 2001 in
      Tianjin. We wanted to evaluate the effectiveness of the strategies related to
      hepatitis A control programs and to provide the basis for further modification of
      the strategies. METHODS: Descriptive epidemiology study was used to analyze the
      hepatitis A epidemic situation in 2000-2011 in Tianjin and to evaluate the
      disease reporting system. Hepatitis A vaccine coverage of target population and
      serum epidemiological study were carried out in 1999, 2005 and 2010 to check on
      the hepatitis A antibody levels so as to evaluate the immuno-barrier condition in
      the normal population. Cox-Stuart test was used to analyze the epidemic trend of
      hepatitis A and other intestinal infectious diseases in Tianjin. RESULTS: The
      incidence rate of hepatitis A decreased from 2.89/100 000 in 2000 to 0.12/100 000
      in 2011, and the percentage of hepatitis A in all types of viral hepatitis
      decreased from 8.02% in 2000 to 0.48% in 2011 in Tianjin. The positive rates of
      hepatitis A antibody also increased in the residents. CONCLUSION: The hepatitis A
      vaccination program was successful in the programs on prevention and control of
      hepatitis A in Tianjin, China.

PMID- 25567019
TI  - [Retrospective analysis of human avian influenza A (H10N8) virus infection in
      Jiangxi province].
AB  - OBJECTIVE: To analyze and discuss the source and epidemic disposition of human
      infection with avian influenza A (H10N8) virus. METHODS: Epidemiological surveys
      were used to collect related data and RT-PCR was applied to detect the specimens
      collected from cases, close contacts related exposure to live poultry markets.
      Data were analyzed descriptively. RESULTS: Three cases were discovered by
      surveillance on patients with severe pneumonia, two of the three died, but one in
      the hospital with the course over 6 months. All the three cases had histories of
      exposure to live poultry or related markets. Lower respiratory tract gargle
      aspirate samples of 3 patients were detected by Nanchang Municipal Center for
      Disease Control and Prevention (CDC) and Jiangxi Provincial CDC, and the results
      showed the influenza 2009pdmH1, H3, H5, H7, H9 subtypes negative. Specimen of
      patient 1 and 2 was positive for influenza A universal primers. Specimen of
      patient 3 was positive for H10N8 detected by Chinese National Influenza Center.
      All 33 close contacts of the patients were negative for H10N8 virus. Positive
      rate of the total poultry environmental specimens collected from the cases
      exposure markets was 5.19%. No new cases were found, after the prevention and
      control messages were implemented. CONCLUSION: Three cases of H10N8 avian
      influenza virus infection province might be associated with exposure to live
      poultry market in Jiangxi.

PMID- 25567020
TI  - [An outbreak of brucellosis in a village in Jiangsu province].
AB  - OBJECTIVE: To investigate the cause and related risk factors of an outbreak
      caused by Brucellosis. METHODS: Epidemiological investigation and laboratory test
      were carried out among occupationally invloved population including sheep
      slaughters and sellers in the village. RESULTS: 18 people were serology positive
      among the 129 occupationally involved persons under survey. Seven of them were
      confirmed cases, 11 were latent infection, to make the overall attack rate as
      14%. 90% of the sheep were from high-risk areas of Brucella. Among the
      occupationally involved persons, 89% of them never wore face masks, 84% never
      wear overalls and 70% never wear gloves. Factors as:work but wearing no gloves
      (RR = 7.4, 95%CI:1.1-53.0), with hand wound (RR = 3.4, 95%CI:1.1-11.0) could
      increase the risk of Brucella infection. CONCLUSION: The cause of this outbreak
      was due to the plentiful influx of unchecked sheep from the northern part of
      China and the employees in the process of sheep slaughtering or trading were lack
      of effective prevention programs.

PMID- 25567021
TI  - [Study on the epidemiologic characteristic of Brucella melitensis isolated in
      Guizhou province in 2010-2012].
AB  - OBJECTIVE: To understand the genetic and epidemiologic characteristic of Brucella
      (B.) melitensis strains isolated in Guizhou province in 2010-2012. METHODS: B.
      genus specific BCSP31-PCR and species-specific AMOS-PCR were used to identify the
      bacteria strain, while the identified strains were analyzed under MLVA-16 and
      cluster analysis of B. melitensis strains. The strains were isolated from Guizhou
      and other provinces. RESULTS: Six B. melitensis strains were identified as B.
      melitensis using the BCSP31-PCR and AMOS-PCR. Data from the MLVA-16 analysis
      revealed the differences of repeated numbers at parts of the VNTR locus in the
      six strains isolated in Guizhou province. The six strains from Guizhou province
      and 105 B. melitensis strains from other province could be divided into 72 MLVA
      types(MT). Strain ZY and ZA from Guizhou province were typed as MT63, and LL3,
      LL4 and LL11 were typed as MT67, while strain SQ was typed as MT72. Data from the
      clustering analysis showed that ZY,ZA, LL3, LL4 and LL9 were most closely
      clustered with B. melitensis isolates from Yunnan, Fujian and Guangdong
      provinces, but strain SQ was genetically remote from other strains. CONCLUSION:
      PCR methods, combined with MLVA-16, identified the six B. melitensis strains
      isolated in Guizhou province in 2010-2012 as B. melitensis biovar 3, with the
      genetic diversity of the strains showed. Six strains were closely related to the
      B. melitensis strains from Yunnan, Fujian and Guangdong provinces. The results of
      this study provided scientific basis for the control and prevention of
      Brucellosis in Guizhou province.

PMID- 25567022
TI  - [The use of ultra deep sequencing technique in the screening program on HIV-1
      drug resistance mutation among ART-naive patients in Hunan province].
AB  - OBJECTIVE: To determine the prevalence rates of nucleotide reverse-transcriptase
      inhibitor (NRTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI)TDRs
      among HIV-1 ART-naive patients in Hunan province using the ultra deep sequencing
      (UDS) technique. METHODS: ART-naive subjects diagnosed in Hunan between 2010 and
      2011 were evaluated by both UDS technique and Sanger sequencing techniques, to
      the 1% variant level. Mutations were scored using the Stanford HIVdb algorithm to
      infer the status on drug resistance. RESULTS: UDS method was performed on 90 ART
      naive subjects that seeking service of care, in Hunan. In total, 42.2% (38/90) of
      the subjects showed major NRTI or nonnucleoside reverse transcriptase inhibitor
      NNRTI TDRs by UDS technique, at a HIV variant frequency level of >=1%, 15.6%
      (14/90) showed NRTI TDR, 16.7% (15/90) showed a major NNRTI TDR and 10% (9/90)
      were both resistant to NRTI and NNRTI when variants were analyzed by Stanford
      HIVdb. CONCLUSION: ART-naive subjects from Hunan province, which had been
      predominately infected by subtype AE, would frequently possess HIV variants with
      NRTI/NNRTI TDRs that would affect the use of first line ART in the region,
      identified by the UDS technique. Further studies were needed to describe the
      prevalence of TDRs and to gather related information.

PMID- 25567023
TI  - [Study on the genotypic characteristics of Japanese encephalitis virus and
      serology in the healthy population of Zhejiang province, 2012-2013].
AB  - OBJECTIVE: To understand the genotypic characteristics and the neutralizing
      antibody levels of Japanese encephalitis virus (JEV) and Japanese encephalitis
      (JE) in both vector mosquitoes and in healthy people of Zhejiang province.
      METHODS: Virus was isolated from mosquitos sampled from the Monitoring Stations
      located in Xianju county during 2012 to 2013. Phylogenetic and homological
      studies were carried out on the E gene. A total of 1 263 blood specimens from 642
      healthy people were collected before and after the seasons of JE epidemics. JEV
      neutralizing antibody was detected by the micro-neutralization test. RESULTS:
      Twenty-five JEV strains were isolated from a total of 11 650 mosquitoes. The
      identity of nucleotide appeared as 87.8%-99.7% both from 2012 to 2013 and from
      1982 to 2010 while as 87.7%-88.0% with vaccine strain SA14-14-2, in Zhejiang. The
      phylogeny tree of E gene indicated that the newly isolated virus belonged to
      genotype I but no mutation of amino acid sequence coding conformational epitope
      was identified in the envelop protein. Both positive rates and the geometric mean
      titer (GMT) of neutralizing antibody in healthy people were 31.5%-42.0% and 1 :
      2.56-1 : 3.53 in Xianju county, during 2012 and 2013, respectively. Both of the
      two positive rates (chi(2)<=1.76, P > 0.05) and the two GMTs (u<=0.64, P > 0.5)
      for antibodies pre or post the epidemic season did not show significant
      differences. CONCLUSION: JEV isolated in Xianju during 2012 and 2013 belonged to
      genotype I. The positive rates of JEV neutralizing antibody from healthy people
      in Xianju were less than 42.0%, which showed no significant differendes pre or
      post JE epidemic season.

PMID- 25567024
TI  - [A nested case-control study in studying the relationship between interleukin-6,
      endothelin-1,E-selectin and the risk of cardio-cerebrovascular events].
AB  - OBJECTIVE: To investigate the relationship between interleukin-6 (IL-6),
      endothelin-1 (ET-1), E-selectin and the risk of cardio-cerebrovascular events.
      METHODS: Based on a cohort study in which 2 589 Mongolians had been followed up
      for 10 years, a nested case-control study was carried out to analyze the
      relationship between IL-6, ET-1, E-selectin and the risk of cardio
      cerebrovascular events. Logistic regression analysis was used to calculate the
      odds ratio (OR) and 95% confidence intervals (95%CI). RESULTS: The average level
      of IL-6 (7.66 vs. 8.77 pg/ml), ET-1 (0.74 vs. 0.75 pg/ml) and E-selectin (17.96
      vs. 18.32 ng/ml)were not significantly different between the case and the control
      groups (P > 0.05). Data from the logistic regression analysis showed that IL-6,
      ET-1 and E-selectin were not significantly associated with the risk of cardio
      cerebrovascular events. The multivariable adjusted ORs (95%CI) on the risk of
      cardio-cerebrovascular events were 0.69 (0.41-1.16), 1.10 (0.66-1.85) and 1.19
      (0.71-2.00) for the participants with IL-6>23.91 pg/ml, ET-1>1.33 pg/ml and E
      selectin>24.43 ng/ml, respectively, compared with those having IL-6<=23.91 pg/ml,
      ET-1<=1.33 pg/ml or E-selectin<=24.43 ng/ml. CONCLUSION: Data from our study
      indicated that the levels of IL-6, ET-1 and E-selectin at baseline were not
      significantly associated with the risk of cardio-cerebrovascular events in people
      from Inner Mongolia.

PMID- 25567025
TI  - [Association between serum uric acid and fasting plasma glucose in middle and
      elderly Chinese].
AB  - OBJECTIVE: To examine the association of fasting plasma glucose (FPG) and serum
      uric acid (SUA) in middle and elderly Chinese. METHODS: 10 413 Guangzhou
      residents aged >=50 were included in the present study. Information on personal
      history, physical examination and biochemical parameters were collected. Subjects
      were grouped by the FPG level, association between FPG and SUA. Levels of
      hyperuricemia (HUA) were evaluated. RESULTS: The SUA levels and the incidence of
      HUA showed trends of increasing, with the increasing FPG levels in women, with
      statistically significant differences seen among all the FPG groups (P value for
      trend<0.05). While the statistical differences of SUA levels and the incidence
      rates of HUA among diabetes group (DM group) and impaired fasting glucose (IFG)
      groups were non-significant (P > 0.05) but it was higher than normal FPG group in
      men (P < 0.05). Logistic regression models were built between various FPG groups
      and HUA. After adjusting for age, smoking status, drinking status, physical
      activity, hypertension, body mass index and the levels of triglyceride and
      creatin. When compared to the normal FPG group, the risk of women suffering from
      HUA increased by 40% (95%CI:1.19-1.64) under the FPG in the range of 6.1-6.9
      mmol/L. Compared to those non-diabetic individuals, the risk of diabetic patients
      suffering from HUA also increased by 44% (95% CI:1.15-1.79) in women. However,
      the risk of suffering from HUA did not relate to the increase of FPG in men.
      CONCLUSION: The SUA level and the incidence of HUA tended to increase along with
      the increasing levels of FPG in middle and elderly Chinese women and the increase
      of FPG might also increase the risk of HUA, but not in men.

PMID- 25567026
TI  - [Body mass index as a moderator of the relationship between chronic disease and
      health-related quality of life].
AB  - OBJECTIVE: To examine the function of body mass index (BMI) as a moderator
      reflecting the relationship between chronic disease and health-related quality of
      life (HRQOL). METHODS: This study included 8 314 participants pooled from a
      general population-based cross-sectional survey that had been conducted in
      Beijing and 8 provinces of China (Jiangsu,Anhui,Gansu, Qinghai, Fujian, Jilin,
      Jiangxi, and Henan). Hierarchical multiple regression was emplayed to test the
      moderating effect. RESULTS: In physical component summary of SF-36, the
      regression coefficient of interaction on chronic disease and BMI was not
      significantly different (beta = 0.084, P = 0.142), while the new DeltaR(2) was
      not significantly different (DeltaR(2) = 0.000, P = 0.142) either. In mental
      component summary of SF-36, the interaction on chronic disease and BMI was
      significantly different (beta = 0.132, P = 0.034), so as the new DeltaR(2)
      (DeltaR(2) = 0.001, P = 0.034). Compared to the standard regression coefficient,
      chronic disease had a greater negative impact on HRQOL than BMI on both physical
      and mental component summaries. CONCLUSION: Our results indicated that BMI could
      moderate the association between chronic disease and HRQOL. The higher the BMI,
      the smaller negative impact of chronic disease on HRQOL in mental component
      summary was seen.

PMID- 25567027
TI  - [Distribution of HIV-1 genotypes in China: a systematic review].
AB  - OBJECTIVE: To provide information on the geographical distribution of HIV-1
      genotypes and subtypes in the population of China. METHODS: A comprehensive
      search was carried out in China Hospital Knowledge Database (CHKD), Wanfang
      (Chinese), CBMDisc and PubMed databases to identify all studies published related
      to HIV-1 genotypes in China. All studies were grouped according to the sites,
      period and objects for analyzing the distribution of HIV genotypes. RESULTS: A
      total of 175 studies were included in this Meta-analysis, which contained 285
      records. We found that the predominate genotypes in China were B' subtype,
      CRF01_AE, CRF07_BC and CRF08_BC, but the subtype distribution of HIV-1 was
      different in the western and southern parts of the country. CRF01_AE had a
      significant increase while subtype B' showed a decrease. There were various HIV-1
      subtypes among individuals who acquired HIV through sexual contacts and CRF01_AE
      was most commonly identified in this group of people. CONCLUSION: The
      distribution of HIV-1 genotypes in Chinese people significantly changed, together
      with high complexity of the HIV-1 epidemics noticed in China.

PMID- 25567028
TI  - [Time-dependent confounding bias and follow-up duration time bias in cohort
      studies].

PMID- 25567029
TI  - [Research progress on the association of ambient air pollution and adverse birth
      outcomes: a review].

PMID- 25567030
TI  - [Psychosocial factors related to the practice of high risk sexual behavior among
      men who have sex with men: a review].

PMID- 25567031
TI  - Brief strategic therapy in first myocardial infarction patients with increased
      levels of stress: a randomized clinical trial.
AB  - BACKGROUND: Little is known about the impact of interventions targeting chronic
      stress levels on clinical outcomes among myocardial infarction (MI) patients with
      increased levels of stress. OBJECTIVES: To examine the impact of the addition of
      brief strategic therapy (BST) to usual care (UC) on clinical outcomes in first MI
      patients with increased levels of stress. DESIGN: Eighty-one patients were
      randomly assigned to BST in conjunction with UC (medical treatment, risk factor
      information, and guidance on unhealthy behavior change) or to UC. METHODS: The
      outcome measures were scores on the Perceived Stress Scale, reinfarction and
      cardiac mortality rates, and scores on the Health Survey. Measures were taken
      before, post-treatment, and at two follow-ups. RESULTS: Patients subjected to BST
      showed reduced perceived stress at post-treatment and maintained decreased levels
      at follow-ups. At 1-year follow-up, they had a lower rate of non-fatal
      reinfarction, and at 2.5-year follow-up, they had a lower rate of fatal
      reinfarction. Their mental and physical health was improved at post-treatment and
      this was sustained at follow-ups. CONCLUSION: The addition of BST to UC favorably
      influences the disease course after MI in patients with increased levels of
      stress.

PMID- 25567032
TI  - Comparison of in silico tools for evaluating rat oral acute toxicity.
AB  - Different in silico models have been developed and implemented for the evaluation
      of mammalian acute toxicity, exploring acute oral toxicity data expressed as
      median lethal dose (LD(50)). We compared five software programs (TOPKAT,
      ACD/ToxSuite, TerraQSAR, ADMET Predictor and T.E.S.T.) using a dataset of 7417
      chemicals. We tested the models' performance using the quantitative results and,
      in classification, the toxicity threshold defined within the Classifying,
      Labelling and Packaging (CLP) regulation. ACD gave the best results with r(2) of
      0.79 and 0.66 accuracy. However, its performance dropped when considering the
      molecules not present in its training set, and the other models behaved
      similarly. We also considered the information on the applicability domain (AD),
      which improved the models' performance, but not enough for the molecules external
      to the models' training set. We also considered the chemical classes and found
      that all models gave high performance for certain classes (e.g. hydrazones and
      sulphides) while other classes were always badly predicted (e.g. aromatic
      secondary amides).

PMID- 25567033
TI  - Rapidly disintegrating vagina retentive cream suppositories of progesterone:
      development, patient satisfaction and in vitro/in vivo studies.
AB  - Our objective was to develop novel vagina retentive cream suppositories (VRCS) of
      progesterone having rapid disintegration and good vaginal retention. VRCS of
      progesterone were prepared using oil in water (o/w) emulsion of mineral oil or
      theobroma oil in hard fat and compared with conventional vaginal suppositories
      (CVS) prepared by hard fat. VRCS formulations were tested for content uniformity,
      disintegration, melting range, in vitro release and stability studies. The most
      stable formulation (VRCS I) was subjected to scaling-up manufacturing and
      patients' satisfaction test. The rapid disintegration, good retentive properties
      are applicable through the inclusion of emulsified theobroma oil rather than
      hydrophilic surfactant into the hard fat bases. The release profile of
      progesterone from VRCS I showed a biphasic pattern due to the formation of
      progesterone reservoir in the emulsified theobroma oil. All volunteers involved
      in patients' satisfaction test showed high satisfactory response to the tested
      formulation (VRCS). The in vivo pharmacokinetic study suggests that VRCS of
      progesterone provided higher rate and extent of absorption compared to hard fat
      based suppositories. Our results proposed that emulsified theobroma oil could be
      promising to solve the problems of poor patients' satisfaction and variability of
      drug absorption associated with hard fat suppositories.

PMID- 25567034
TI  - Elevated levels of carbonyl proteins in cerebrospinal fluid of patients with
      neurodegenerative diseases.
AB  - The importance of oxidative stress in the pathogenesis of neuroimmunological and
      neurodegenerative diseases, such as multiple sclerosis (MS), has been discussed
      for a long time. However, markers for oxidative stress in cerebrospinal fluid are
      hardly detected. The aim of the present study is to assess whether carbonyl
      proteins as end products of metabolic processes may serve as a marker for
      oxidative stress in the cerebrospinal fluid (CSF) of patients with
      neuroimmunological and neurodegenerative diseases. Levels of carbonyl proteins in
      the CSF were assessed in 15 patients suffering from MS, four patients with
      neurodegenerative diseases, including one patient with dementia complicated by
      carcinomatous meningitis due to breast cancer, and four control subjects with no
      established neurological disease. Levels of carbonyl proteins were measured with
      a commercially available KIT. A significant difference (P = 0.025) was shown for
      mean values of various subgroups with highest levels for patients with
      neurodegenerative diseases (756.1 pmol/mg), followed by the MS (630.8 pmol/mg)
      and the control group (356.5 pmol/mg). Post-hoc pair wise comparisons showed
      significant differences between the MS group and healthy controls (P = 0.016) as
      well as for patients with neurodegenerative diseases and healthy controls (P =
      0.02). This pilot trial showed that carbonyl proteins might serve as measure for
      oxidative stress in the CSF of relapsing as well as progressive MS patients and
      in patients with neurodegenerative diseases. Larger trials have to show whether
      they may serve as biomarkers and be helpful in monitoring patients with MS or
      neurodegenerative diseases. 

PMID- 25567035
TI  - Carbon dots rooted agarose hydrogel hybrid platform for optical detection and
      separation of heavy metal ions.
AB  - A robust solid sensing platform for an on-site operational and accurate detection
      of heavy metal is still a challenge. We introduce chitosan based carbon dots
      rooted agarose hydrogel film as a hybrid solid sensing platform for detection of
      heavy metal ions. The fabrication of the solid sensing platform is centered on
      simple electrostatic interaction between the NH3+ group present in the carbon
      dots and the OH- groups present in agarose. Simply on dipping the hydrogel film
      strip into the heavy metal ion solution, in particular Cr6+, Cu2+, Fe3+, Pb2+,
      Mn2+, the strip displays a color change, viz., Cr6+->yellow, Cu2+->blue, Fe3+
      >brown, Pb2+->white, Mn2+->tan brown. The optical detection limit of the
      respective metal ion is found to be 1 pM for Cr6+, 0.5 MUM for Cu2+, and 0.5 nM
      for Fe3+, Pb2+, and Mn2+ by studying the changes in UV-visible reflectance
      spectrum of the hydrogel film. Moreover, the hydrogel film finds applicability as
      an efficient filtration membrane for separation of these quintet heavy metal
      ions. The strategic fundamental feature of this sensing platform is the
      successful capability of chitosan to form colored chelates with transition
      metals. This proficient hybrid hydrogel solid sensing platform is thus the most
      suitable to employ as an on-site operational, portable, cheap colorimetric
      optical detector of heavy metal ion with potential skill in their separation.
      Details of the possible mechanistic insight into the colorimetric detection and
      ion separation are also discussed.

PMID- 25567036
TI  - Diversity and impact of rare variants in genes encoding the platelet G protein
      coupled receptors.
AB  - Platelet responses to activating agonists are influenced by common population
      variants within or near G protein-coupled receptor (GPCR) genes that affect
      receptor activity. However, the impact of rare GPCR gene variants is unknown. We
      describe the rare single nucleotide variants (SNVs) in the coding and splice
      regions of 18 GPCR genes in 7,595 exomes from the 1,000-genomes and Exome
      Sequencing Project databases and in 31 cases with inherited platelet function
      disorders (IPFDs). In the population databases, the GPCR gene target regions
      contained 740 SNVs (318 synonymous, 410 missense, 7 stop gain and 6 splice
      region) of which 70 % had global minor allele frequency (MAF) < 0.05 %.
      Functional annotation using six computational algorithms, experimental evidence
      and structural data identified 156/740 (21 %) SNVs as potentially damaging to
      GPCR function, most commonly in regions encoding the transmembrane and C-terminal
      intracellular receptor domains. In 31 index cases with IPFDs (Gi-pathway defect
      n=15; secretion defect n=11; thromboxane pathway defect n=3 and complex defect
      n=2) there were 256 SNVs in the target regions of 15 stimulatory platelet GPCRs
      (34 unique; 12 with MAF< 1 % and 22 with MAF>= 1 %). These included rare variants
      predicting R122H, P258T and V207A substitutions in the P2Y12 receptor that were
      annotated as potentially damaging, but only partially explained the platelet
      function defects in each case. Our data highlight that potentially damaging
      variants in platelet GPCR genes have low individual frequencies, but are
      collectively abundant in the population. Potentially damaging variants are also
      present in pedigrees with IPFDs and may contribute to complex laboratory
      phenotypes. 

PMID- 25567037
TI  - Comparison of two dose and three dose human papillomavirus vaccine schedules:
      cost effectiveness analysis based on transmission model.
AB  - OBJECTIVE: To investigate the incremental cost effectiveness of two dose human
      papillomavirus vaccination and of additionally giving a third dose. DESIGN: Cost
      effectiveness study based on a transmission dynamic model of human papillomavirus
      vaccination. Two dose schedules for bivalent or quadrivalent human papillomavirus
      vaccines were assumed to provide 10, 20, or 30 years' vaccine type protection and
      cross protection or lifelong vaccine type protection without cross protection.
      Three dose schedules were assumed to give lifelong vaccine type and cross
      protection. SETTING: United Kingdom. POPULATION: Males and females aged 12-74
      years. INTERVENTIONS: No, two, or three doses of human papillomavirus vaccine
      given routinely to 12 year old girls, with an initial catch-up campaign to 18
      years. MAIN OUTCOME MEASURE: Costs (from the healthcare provider's perspective),
      health related utilities, and incremental cost effectiveness ratios. RESULTS:
      Giving at least two doses of vaccine seems to be highly cost effective across the
      entire range of scenarios considered at the quadrivalent vaccine list price of
      L86.50 (?109.23; $136.00) per dose. If two doses give only 10 years' protection
      but adding a third dose extends this to lifetime protection, then the third dose
      also seems to be cost effective at L86.50 per dose (median incremental cost
      effectiveness ratio L17,000, interquartile range L11,700-L25,800). If two doses
      protect for more than 20 years, then the third dose will have to be priced
      substantially lower (median threshold price L31, interquartile range L28-L35) to
      be cost effective. Results are similar for a bivalent vaccine priced at L80.50
      per dose and when the same scenarios are explored by parameterising a Canadian
      model (HPV-ADVISE) with economic data from the United Kingdom. CONCLUSIONS: Two
      dose human papillomavirus vaccine schedules are likely to be the most cost
      effective option provided protection lasts for at least 20 years. As the precise
      duration of two dose schedules may not be known for decades, cohorts given two
      doses should be closely monitored.

PMID- 25567038
TI  - The gut microbiota and inflammatory noncommunicable diseases: associations and
      potentials for gut microbiota therapies.
AB  - Rapid environmental transition and modern lifestyles are likely driving changes
      in the biodiversity of the human gut microbiota. With clear effects on
      physiologic, immunologic, and metabolic processes in human health, aberrations in
      the gut microbiome and intestinal homeostasis have the capacity for multisystem
      effects. Changes in microbial composition are implicated in the increasing
      propensity for a broad range of inflammatory diseases, such as allergic disease,
      asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable
      diseases (NCDs). There are also suggestive implications for neurodevelopment and
      mental health. These diverse multisystem influences have sparked interest in
      strategies that might favorably modulate the gut microbiota to reduce the risk of
      many NCDs. For example, specific prebiotics promote favorable intestinal
      colonization, and their fermented products have anti-inflammatory properties.
      Specific probiotics also have immunomodulatory and metabolic effects. However,
      when evaluated in clinical trials, the effects are variable, preliminary, or
      limited in magnitude. Fecal microbiota transplantation is another emerging
      therapy that regulates inflammation in experimental models. In human subjects it
      has been successfully used in cases of Clostridium difficile infection and IBD,
      although controlled trials are lacking for IBD. Here we discuss relationships
      between gut colonization and inflammatory NCDs and gut microbiota modulation
      strategies for their treatment and prevention. 

PMID- 25567039
TI  - Update on epigenetics in allergic disease.
AB  - Chronic inflammatory diseases, including allergies and asthma, are the result of
      complex gene-environment interactions. One of the most challenging questions in
      this regard relates to the biochemical mechanism of how exogenous environmental
      trigger factors modulate and modify gene expression, subsequently leading to the
      development of chronic inflammatory conditions. Epigenetics comprises the
      umbrella of biochemical reactions and mechanisms, such as DNA methylation and
      chromatin modifications on histones and other structures. Recently, several
      lifestyle and environmental factors have been investigated in terms of such
      biochemical interactions with the gene expression-regulating machinery:
      allergens; microbes and microbial compounds; dietary factors, including vitamin
      B12, folic acid, and fish oil; obesity; and stress. This article aims to update
      recent developments in this context with an emphasis on allergy and asthma
      research. 

PMID- 25567041
TI  - Making it big in allergy.

PMID- 25567040
TI  - The microbiome in asthma.
AB  - The application of recently developed sensitive, specific, culture-independent
      tools for identification of microbes is transforming concepts of microbial
      ecology, including concepts of the relationships between the vast complex
      populations of microbes associated with ourselves and with states of health and
      disease. Although most work initially focused on the community of microbes
      (microbiome) in the gastrointestinal tract and its relationship to
      gastrointestinal disease, interest has expanded to include study of the
      relationships of the airway microbiome to asthma and its phenotypes and to the
      relationships between the gastrointestinal microbiome, development of immune
      function, and predisposition to allergic sensitization and asthma. Here we
      provide our perspective on the findings of studies of differences in the airway
      microbiome between asthmatic patients and healthy subjects and of studies of
      relationships between environmental microbiota, gut microbiota, immune function,
      and asthma development. In addition, we provide our perspective on how these
      findings suggest the broad outline of a rationale for approaches involving
      directed manipulation of the gut and airway microbiome for the treatment and
      prevention of allergic asthma.

PMID- 25567044
TI  - Defining phenotypes in rhinitis: a step toward personalized medicine.

PMID- 25567042
TI  - Advances in adult asthma diagnosis and treatment in 2014.
AB  - In 2014, new biologic therapies are emerging for severe asthma based on
      identification of relevant phenotypes. The exploration of nutritional supplements
      to treat asthma has been less successful. 

PMID- 25567047
TI  - A hierarchical model of factors influencing a battery of agility tests.
AB  - AIM: The aim of this study was to investigate the hierarchical contributions of
      anthropometry, strength and cognition to a battery of prescriptive and reactive
      agility tests. METHODS: Nineteen participants (mean+/-S.D.; age:22.1+/-1.9 years;
      height: 182.9+/-5.5 cm; body mass: 77+/-4.9 kg) completed four agility tests: a
      prescriptive linear sprint, a prescriptive change-of-direction sprint, a reactive
      change-of-direction sprint, and a reactive linear deceleration test.
      Anthropometric variables included body fat percentage and thigh girth. Strength
      was quantified as the peak eccentric hamstring torque at 180, 300, and 60 degrees
      .s-1. Mean reaction time and accuracy in the Stroop word-colour Test was used to
      assess perceptual and decision making factors. RESULTS: There was little evidence
      of intertest correlation with the strongest relationship observed between 10 m
      sprint and t-test performance (r2=0.49, P<0.01). Anthropometric measures were not
      strong predictors of agility, accounting for a maximum 23% (P=0.12) in the
      prescriptive change-of-direction test. Cognitive measures had a stronger
      correlation with the reactive (rather than prescriptive) agility tests, with a
      maximum 33% (P=0.04) of variance accounted for in the reactive change-of
      direction test. Eccentric hamstring strength accounted for 62% (P=0.01) of the
      variance in the prescriptive change-of-direction test. Hierarchical ordering of
      the agility tests revealed that eccentric hamstring strength was the primary
      predictor in 3 of the 4 tests, with cognitive accuracy the next most common
      predictor. CONCLUSION: There is little evidence of inter-test correlation across
      a battery of agility tests. Eccentric hamstring strength and decision making
      accuracy are the most common predictors of agility performance.

PMID- 25567045
TI  - Identification of novel immune and barrier genes in atopic dermatitis by means of
      laser capture microdissection.
AB  - BACKGROUND: The molecular signature of atopic dermatitis (AD) lesions is
      associated with TH2 and TH22 activation and epidermal alterations. However, the
      epidermal and dermal AD transcriptomes and their respective contributions to
      abnormalities in respective immune and barrier phenotypes are unknown. OBJECTIVE:
      We sought to establish the genomic profile of the epidermal and dermal
      compartments of lesional and nonlesional AD skin compared with normal skin.
      METHODS: Laser capture microdissection was performed to separate the epidermis
      and dermis of lesional and nonlesional skin from patients with AD and normal skin
      from healthy volunteers, followed by gene expression (microarrays and real-time
      PCR) and immunostaining studies. RESULTS: Our study identified novel immune and
      barrier genes, including the IL-34 cytokine and claudins 4 and 8, and showed
      increased detection of key AD genes usually undetectable on arrays (ie, IL22,
      thymic stromal lymphopoietin [TSLP], CCL22, and CCL26). Overall, the combined
      epidermal and dermal transcriptomes enlarged the AD transcriptome, adding 674
      upregulated and 405 downregulated differentially expressed genes between lesional
      and nonlesional skin to the AD transcriptome. We were also able to localize
      individual transcripts as primarily epidermal (defensin, beta 4A [DEFB4A]) or
      dermal (IL22, cytotoxic T-lymphocyte antigen 4 [CTLA4], and CCR7) and link their
      expressions to possible cellular sources. CONCLUSIONS: This is the first report
      that establishes robust epidermal and dermal genomic signatures of lesional and
      nonlesional AD skin and normal skin compared with whole tissues. These data
      establish the utility of laser capture microdissection to separate different
      compartments and cellular subsets in patients with AD, allowing localization of
      key barrier or immune molecules and enabling detection of gene products usually
      not detected on arrays.

PMID- 25567048
TI  - T-Shirt fabric and color affect the physiological strain but not 10 km outdoor
      running performance.
AB  - BACKGROUND: The aim of the present study was to evaluate the effects of T-Shirt
      fabric and color on the 10 km outdoor running performance. METHODS: Six men and
      six women (mean+/-SD: age: 27+/-5 years; height: 1.70+/-0.13 m; weight: 64.0+/
      12.7 kg; body surface area: 1.73+/-0.29 m2; Sigmaskinfolds: 107+/-24 mm; VO2max:
      40.2+/-8.4 mL.kg-1.min-1) took part in five experimental trials, during each of
      which they wore: 1) no T-shirt (CON); 2) white polyester T-shirt (WP); 3) black
      polyester T-shirt (BP); 4) white cotton T-shirt (WC); and 5) black cotton T-shirt
      (BC). Average running velocity (pace) was calculated from each 2 km running time.
      Rectal, skin and T-shirt temperatures, heart rates and Physiological Strain Index
      (PSI) were measured before and after the 10 km runs and at the end of each 2 km.
      RESULTS: There were no differences in pace, heart rate, rectal and skin
      temperatures among conditions (P>0.05). PSI was higher in BC and WC conditions
      when compared to BP and WP conditions. T-shirt temperature was higher for the BC
      when compared to WP, BP and WC conditions. Rectal temperature and heart rate
      increased simultaneously with reduced pace throughout self-paced running
      (P<0.05). CONCLUSIONS: Despite fabric type T-shirt altered PSI, running
      performance in the 10 km run was not affected by T-shirt type or color.

PMID- 25567046
TI  - Distinct parameters of the basophil activation test reflect the severity and
      threshold of allergic reactions to peanut.
AB  - BACKGROUND: The management of peanut allergy relies on allergen avoidance and
      epinephrine autoinjector for rescue treatment in patients at risk of anaphylaxis.
      Biomarkers of severity and threshold of allergic reactions to peanut could
      significantly improve the care for patients with peanut allergy. OBJECTIVE: We
      sought to assess the utility of the basophil activation test (BAT) to predict the
      severity and threshold of reactivity to peanut during oral food challenges
      (OFCs). METHODS: The severity of the allergic reaction and the threshold dose
      during OFCs to peanut were determined. Skin prick tests, measurements of specific
      IgE to peanut and its components, and BATs to peanut were performed on the day of
      the challenge. RESULTS: Of the 124 children submitted to OFCs to peanut, 52
      (median age, 5 years) reacted with clinical symptoms that ranged from mild oral
      symptoms to anaphylaxis. Severe reactions occurred in 41% of cases, and 57%
      reacted to 0.1 g or less of peanut protein. The ratio of the percentage of
      CD63(+) basophils after stimulation with peanut and after stimulation with anti
      IgE (CD63 peanut/anti-IgE) was independently associated with severity (P = .001),
      whereas the basophil allergen threshold sensitivity CD-sens (1/EC50 * 100, where
      EC50 is half maximal effective concentration) value was independently associated
      with the threshold (P = .020) of allergic reactions to peanut during OFCs.
      Patients with CD63 peanut/anti-IgE levels of 1.3 or greater had an increased risk
      of severe reactions (relative risk, 3.4; 95% CI, 1.8-6.2). Patients with a CD
      sens value of 84 or greater had an increased risk of reacting to 0.1 g or less of
      peanut protein (relative risk, 1.9; 95% CI, 1.3-2.8). CONCLUSIONS: Basophil
      reactivity is associated with severity and basophil sensitivity is associated
      with the threshold of allergic reactions to peanut. CD63 peanut/anti-IgE and CD
      sens values can be used to estimate the severity and threshold of allergic
      reactions during OFCs.

PMID- 25567049
TI  - Eight weeks of a combination of high intensity interval training and conventional
      training reduce visceral adiposity and improve physical fitness: a group-based
      intervention.
AB  - BACKGROUND: High intensity interval training (HIIT) has been recently promoted as
      an effective, low volume and time-efficient training method for improving fitness
      and health related parameters. The aim of the current study was to examine the
      effect of a combination of a group-based HIIT and conventional gym training on
      physical fitness and body composition parameters in healthy adults. METHODS:
      Thirty nine healthy adults volunteered to participate in this eight-week
      intervention study. Twenty three participants performed regular gym training 4
      days a week (C group), whereas the remaining 16 participants engaged twice a week
      in HIIT and twice in regular gym training (HIIT-C group) as the other group.
      Total body fat and visceral adiposity levels were calculated using bioelectrical
      impedance analysis. Physical fitness parameters such as cardiorespiratory
      fitness, speed, lower limb explosiveness, flexibility and isometric arm strength
      were assessed through a battery of field tests. RESULTS: Both exercise programs
      were effective in reducing total body fat and visceral adiposity (P<0.05) and
      improving handgrip strength, sprint time, jumping ability and flexibility
      (P<0.05) whilst only the combination of HIIT and conventional training improved
      cardiorespiratory fitness levels (P<0.05). A between of group changes analysis
      revealed that HIIT-C resulted in significantly greater reduction in both
      abdominal girth and visceral adiposity compared with conventional training
      (P<0.05). CONCLUSIONS: Eight weeks of combined group-based HIIT and conventional
      training improve various physical fitness parameters and reduce both total and
      visceral fat levels. This type of training was also found to be superior compared
      with conventional exercise training alone in terms of reducing more visceral
      adiposity levels. Group-based HIIT may consider as a good methods for individuals
      who exercise in gyms and craving to acquire significant fitness benefits in
      relatively short period of time.

PMID- 25567050
TI  - Self-controlled case-series study to verify the effect of adherence to Beta
      blockers in secondary prevention of myocardial infarction.
AB  - BACKGROUND: Beta-blockers (BB) are recommended in secondary prevention of acute
      myocardial infarction (AMI), but adherence to prescription medication is a
      recognized problem. Most literature on the consequences of poor adherence to
      prescribed BB is limited by the possibility of "healthy adherer bias" and better
      designed studies have been advocated. METHODS AND RESULTS: We investigated the
      association between adherence to BB prescription and risk of subsequent AMIs
      using the self-controlled case series design, which allows improved control of
      interpersonal confounding, being based on intrapersonal comparisons. From all the
      30 089 patients hospitalized for AMI in the years 2009-2011 in an Italian region
      we selected those that suffered subsequent AMIs at days 31 to 365 from discharge
      (1328), and then the 1207 that had at least one BB prescription collected at any
      of the regional pharmacies. Using information on prescriptions, each individual's
      observation time was then divided into periods exposed or unexposed to BB and the
      relative AMI incidence rate ratios (IRR) of BB exposure were estimated by
      conditional Poisson regression. The IRR (rate of recurrent AMI in exposed versus
      unexposed periods) was 0.79 (95% CI 0.69 to 0.90, P=0.001). Various sensitivity
      analyses confirmed the robustness to possible failure of assumptions, ie,
      considering only first recurrences (IRR 0.76, 95% CI 0.66 to 0.88, P<0.001),
      excluding cardiovascular fatalities (IRR 0.76, 95% CI 0.65 to 0.89, P<0.001), and
      excluding individuals with long hospital admissions (IRR 0.60, 95% CI 0.43 to
      0.83, P=0.002). CONCLUSIONS: Adherence to recommended BB therapy was associated
      with a 20% reduction of recurrent AMIs, consistently with previous research, but
      with decreased concerns about healthy-adherer bias.

PMID- 25567051
TI  - Effect of a moderate fat diet with and without avocados on lipoprotein particle
      number, size and subclasses in overweight and obese adults: a randomized,
      controlled trial.
AB  - BACKGROUND: Avocados are a nutrient-dense source of monounsaturated fatty acids
      (MUFA) that can be used to replace saturated fatty acids (SFA) in a diet to lower
      low density lipoprotein cholesterol (LDL-C). Well-controlled studies are lacking
      on the effect of avocado consumption on cardiovascular disease (CVD) risk
      factors. METHODS AND RESULTS: A randomized, crossover, controlled feeding trial
      was conducted with 45 overweight or obese participants with baseline LDL-C in the
      25th to 90th percentile. Three cholesterol-lowering diets (6% to 7% SFA) were fed
      (5 weeks each): a lower-fat diet (LF: 24% fat); 2 moderate-fat diets (34% fat)
      provided similar foods and were matched for macronutrients and fatty acids: the
      avocado diet (AV) included one fresh Hass avocado (136 g) per day, and the
      moderate-fat diet (MF) mainly used high oleic acid oils to match the fatty acid
      content of one avocado. Compared with baseline, the reduction in LDL-C and non
      high-density lipoprotein (HDL) cholesterol on the AV diet (-13.5 mg/dL, -14.6
      mg/dL) was greater (P<0.05) than the MF (-8.3 mg/dL, -8.7 mg/dL) and LF (-7.4
      mg/dL, -4.8 mg/dL) diets. Furthermore, only the AV diet significantly decreased
      LDL particle number (LDL-P, -80.1 nmol/L, P=0.0001), small dense LDL cholesterol
      (LDL(3+4), -4.1 mg/dL, P=0.04), and the ratio of LDL/HDL (-6.6%, P<0.0001) from
      baseline. CONCLUSIONS: Inclusion of one avocado per day as part of a moderate
      fat, cholesterol-lowering diet has additional LDL-C, LDL-P, and non-HDL-C
      lowering effects, especially for small, dense LDL. Our results demonstrate that
      avocados have beneficial effects on cardio-metabolic risk factors that extend
      beyond their heart-healthy fatty acid profile. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01235832.

PMID- 25567053
TI  - Bacterial Pathogen Helicobacter pylori: A Bad AKTor Inhibits p53 Protein Activity
      [corrected].

PMID- 25567054
TI  - Distribution characteristics of pollutant transport in a turbulent two-phase
      flow.
AB  - The distribution characteristics of pollutants released at varied rates and
      different vertical inlet positions of an open channel are investigated via a
      three-dimensional numerical model. Pollutants are injected from time-dependent
      sources in a turbulent free-surface flow. Numerical computations were carried out
      using Fluent 6.3, which is based on the finite volume approach. The air/water
      interface was modeled with the volume of fluid method (VOF). By focusing on
      investigating the influences of the flow on pollutants, it is found that with an
      increase of the injection rate, the pollutant concentration increases along the
      channel and the longitudinal dispersion is higher. On the other hand, it is noted
      that the point of injection modifies significantly the dispersion pattern of
      pollutant. These findings may be of great help in cost-effective scientific
      countermeasures to be taken into account for accident or planned pollutants
      discharged into a river. 

PMID- 25567052
TI  - Hepatitis B Virus Core Promoter A1762T/G1764A (TA)/T1753A/T1768A Mutations
      Contribute to Hepatocarcinogenesis by Deregulating Skp2 and P53.
AB  - BACKGROUND AND AIM: Hepatitis B virus core promoter (CP) mutations can increase
      risk of hepatocellular carcinoma. The CP region overlaps with the HBV X (HBx)
      gene, which has been associated with hepatocarcinogenesis. The cyclin kinase
      inhibitor P53 is an important regulator of cell cycle progression. We determined
      whether HBx mutants that result from mutations in the CP deregulate P53. METHODS:
      A HBx combination (combo) mutant with changes in the CP region that corresponded
      to A1762T/G1764A (TA), T1753A, and T1768A was constructed and expressed in L-02
      and Hep3B cells. The effects of CP mutations on expression and degradation of
      P53, and the effects on cell cycle progression and proliferation were analyzed.
      RESULTS: The combo mutant decreased levels of P53 and increased cyclin D1
      expression, accelerated P53 degradation in L-02 cells, accelerated cell cycle
      progression, and increased expression of S-phase kinase-associated protein 2
      (Skp2) in L-02 and Hep3B cells. Silencing of Skp2 abrogated the effects of CP
      mutations on P53 expression. The kinetics of P53 expression correlated with
      changes in cell cycle distribution. CONCLUSIONS: The HBx mutant with a
      combination of CP mutations can up-regulate Skp2, which then down-regulates P53
      via ubiquitin-mediated proteasomal degradation, increasing the risk of
      hepatocellular carcinoma.

PMID- 25567055
TI  - Carbon decomposition by inoculating Phanerochaete chrysosporium during drum
      composting of agricultural waste.
AB  - The effect of Phanerochaete chrysosporium inoculation during drum composting of
      agricultural waste was performed at different composting stages. Three trials
      were carried out with (5:4:1) combination of vegetable waste, cattle manure, and
      sawdust along with 10 kg of dried leaves with a total mass of 100 kg in a 550 L
      rotary drum composter. Trial 1 was a control without inoculation of fungus, while
      trial 2 was inoculated during the initial day (0th day of composting), and trial
      3 was inoculated after the thermophilic phase, i.e., on the 8th day of composting
      period. The inoculation of fungus increased the volatile solids reduction by 1.45
      fold in trial 2 and 1.7-fold in trial 3 as compared to trial 1 without any fungal
      inoculation. Total Kjeldahl Nitrogen (TKN) was observed with 2.31, 2.62, and
      2.59% in trials 1, 2, and 3, respectively, at the end of 20 days of composting
      period. Hence, it can be concluded that inoculation of white-rot fungus increased
      the decomposition rate of agricultural waste within shorter time in drum
      composting. However, inoculation after the thermophilic phase was found more
      effective than inoculation during initial days of composting for producing more
      stabilized and nutrient-rich compost.

PMID- 25567056
TI  - Does the exposure mode to ENPs influence their toxicity to aquatic species? A
      case study with TiO2 nanoparticles and Daphnia magna.
AB  - Recent studies suggest that the ecotoxicity of engineered nanoparticles (ENPs) is
      dependent upon the treatment of ENPs in suspensions (e.g. sonication or use of
      solvents) and on the mode of exposure to test organisms. We conducted several
      bioassays with Daphnia magna in order to determine how adverse effects of TiO2
      nanoparticles (n-TiO2) are influenced by experimental set-up. Several treatments
      were applied, including three test media, several treatments of n-TiO2
      suspensions (stirring, sonication) and different exposure modes (exposure
      duration and volume of test suspension). No adverse effects were observed when D.
      magna were exposed to 50 mL of suspension, regardless of TiO2 concentration (up
      to 250 mg/L) and exposure duration. Conversely, adverse effects were observed
      when D. magna were exposed to 2 mL of suspension for 96 h with a 50 % effect
      concentration EC50 values ranging from 32 mg/L to 82 mg/L. Test media had no
      significant influence on the outcome of all treatments. For a better mechanistic
      understanding of the experimental set-up at which adverse effects were observed,
      the particle size of n-TiO2 in the test media was characterized throughout the
      test duration. These measurements revealed a fast and strong agglomeration with a
      secondary particle size in the order of magnitude of micrometers. Our study
      describes how the effects of n-TiO2 on D .magna are influenced by the duration of
      exposure and volume of media, highlighting the need for standardization of
      experimental methods. 

PMID- 25567058
TI  - An analytical deterministic model for simultaneous phytoremediation of Ni and Cd
      from contaminated soils.
AB  - Soil contamination by heavy metals, due to human activities, is not often limited
      to a single contaminant. The objective of this study was to develop a simple
      model for phytoextracting separate and combined Ni and Cd from contaminated
      soils. The study was further aimed to study phytoextraction potential of
      ornamental kale and land cress grown in soils contaminated with separate and
      combined Ni and Cd metals. The results indicated that elevated Ni and Cd
      concentrations in soil inhibit growth of both ornamental kale and land cress
      plants. In Ni + Cd treatments, growth and development of both plants were more
      affected than in either Ni or Cd treatments. Further, in Ni + Cd treatments, Ni
      concentration in tissues of both plants was increased by increasing soil Ni
      concentration under various Cd concentrations. At constant Ni concentration,
      addition of Cd did not appreciably changed Ni content of plant tissues. Land
      cress demonstrated higher tolerance to soil contamination by Ni and Cd compared
      to ornamental kale. It also demonstrated higher phytoextraction potential for
      soil Cd than ornamental kale. Enhanced bioavailability of Ni and Cd ions, due to
      competitive adsorption and desorption reactions, had no reasonable effect on
      metal ion accumulation in plant tissues. This indicates that at relatively high
      soil contamination, metal ion adsorption is no longer a limiting factor for
      phytoremediation. The newly proposed model, which assumes that metal uptake rate
      inversely depends on total soil metal ion concentration, reasonably well
      predicted the cleanup time of Ni, Cd, and Ni at the presence of Cd from the
      contaminated soils. The model also predicts that phytoremediation process takes
      much longer time when soil is contaminated by multi-metal ions. 

PMID- 25567057
TI  - Acetylcholinesterase in zebrafish embryos as a tool to identify neurotoxic
      effects in sediments.
AB  - In order to clarify the suitability of zebrafish (Danio rerio) embryos for the
      detection of neurotoxic compounds, the acetylcholinesterase assay was adapted and
      validated with a series of priority pollutants listed as relevant for the
      European water policy (Aroclor 1254, 2,3-benzofuran, bisphenol A, chlorpyrifos,
      paraoxon-methyl, quinoline, and methyl mercury chloride) as well as acetonic
      extracts from three sediments of known contamination. The acute toxicities of the
      model substances and the sediment extracts were determined by means of the fish
      embryo test as specified in OECD TG 236, and concentrations as low as the
      effective concentration at 10% inhibition (EC10) were used as the highest test
      concentration in the acetylcholinesterase test in order to avoid nonspecific
      systemic effects mimicking neurotoxicity. Among the model compounds, only the
      known acetylcholinesterase inhibitors paraoxon-methyl and chlorpyrifos produced a
      strong inhibition to about 20 and 33%, respectively, of the negative controls.
      For the sediment extracts, a reduction of acetylcholinesterase activity to about
      60% could only be shown for the Vering Canal sediment extracts; this could be
      correlated to high contents of acetylcholinesterase-inhibiting polycyclic
      aromatic hydrocarbons (PAHs) as identified by chemical analyses. Co-incubation of
      the Vering Canal sediment extracts with chlorpyrifos at EC10 concentrations each
      did not significantly increase the inhibitory effect of chlorpyrifos, indicating
      that the mode of action of acetylcholinesterase inhibition by the sediment-borne
      PAHs is different to that of the typical acetylcholinesterase blocker
      chlorpyrifos. Overall, the study documents that zebrafish embryos represent a
      suitable model not only to reveal acetylcholinesterase inhibition, but also to
      investigate various modes of neurotoxic action.

PMID- 25567059
TI  - Biodegradation of a biochar-modified waterborne polyacrylate membrane coating for
      controlled-release fertilizer and its effects on soil bacterial community
      profiles.
AB  - Biochar-modified polyacrylate-like polymers are promising waterborne polymer
      based membrane coatings for controlled-release fertilizers. However, the effect
      of these membrane polymers on paddy soil is unknown. A soil incubation experiment
      was conducted using Fourier transform infrared photoacoustic spectroscopy to
      monitor the changes in the polymer-coated membranes in paddy soil, and Biolog
      EcoPlates and polymerase chain reaction-denaturing gradient gel electrophoresis
      were used to detect the effects of the membranes on soil bacterial community
      profiles. Compared to unmodified membranes, the biodegradation rate of the
      biochar-modified membrane was slower, and the membrane was more intact, which
      improved and guaranteed the controlled release of nutrients. Compared to the soil
      without membranes, the biochar-modified membranes, as well as unmodified ones,
      showed no significant impacts on the composition diversity of soil dominant
      bacterial community. The activity and functional diversity of soil culturable
      microbial community during the early stage of incubation were reduced by biochar
      modified membranes due to the release of small amount of soluble organic
      materials but were both recovered in the 12(th) month of the incubation period.
      Therefore, the biochar-modified waterborne polyacrylate was environmentally
      friendly, demonstrating its potential both in the development of coated
      controlled-release fertilizers and in the utilization of crop residue. 

PMID- 25567060
TI  - Assessment of heavy metal contamination in Hediste diversicolor (O.F. Muller,
      1776), Mugil cephalus (Linnaeus, 1758), and surface sediments of Bafa Lake
      (Eastern Aegean).
AB  - In the present study, the bioaccumulation of six heavy metals (Cd, Cr, Cu, Hg,
      Pb, and Zn) in Hediste (Nereis) diversicolor (O.F. Muller, 1776) and also in the
      muscle and liver of Mugil cephalus (Linnaeus, 1758) collected from seven stations
      in the Bafa Lake was investigated. Sediment samples were also collected in each
      site to assess heavy metal levels and to provide additional information on
      pollution of the lake. The mean concentrations of heavy metals in sediment, H.
      diversicolor, and muscle and liver of the fish were found to be in the magnitude
      of Cr>Pb>Zn>Cu>Cd>Hg, Zn>Cu>Cr>Pb>Hg>Cd, Zn>Cu>Pb>Cr >Hg>Cd, and
      Cu>Zn>Cr>Cd>Pb>Hg, respectively. Hg, Cu, and Zn in H. diversicolor and Hg and Zn
      in muscle and also Hg, Cd, Cu, and Zn in liver of fish accumulated in a higher
      degree than in sediment. There was no clear relationship between metal
      concentrations in sediments, polychaetes, and fish, except Cr. According to
      international criteria and Turkish regulations, Pb and Zn values in edible muscle
      of the fish collected from stations S6 and S5 exceeded the food safety limits,
      respectively. The results of this study suggest that these sentinel species can
      be considered as good anthropogenic biological indicators for heavy metal
      pollution along the Bafa Lake. 

PMID- 25567061
TI  - Enhancement of cadmium tolerance and accumulation by introducing Perilla
      frutescens (L.) Britt var. frutescens genes in Nicotiana tabacum L. plants.
AB  - The tobacco has the genetic potential to remove toxic metals from the soil. To
      develop hyperaccumulating tobacco plants, distant hybridization between tobacco
      (Nicotiana tabacum L.), a high-biomass crop, and Perilla frutescens (L.) Britt
      var. frutescens, a newfound Cd-hyperaccumulator species, was carried out using a
      novel method viz. pollination following grafting. Their hybrid nature was
      preliminarily confirmed by phenotype, isozyme pattern, random amplified
      polymorphic DNA (RAPD) and metabolites analysis. About 120 putative F2 hybrids
      derived from the cross-combination [(N. sylvestris Speg. & Comes rootstock + N.
      tabacum L. var. 78-04 scion) * P. frutescens (L.) Britt var. frutescens] were
      then subjected to up to 300 MUM CdCl2 in hydroponic conditions for 10 days.
      Results showed five seedlings were more resistant to Cd than female parent and
      accumulated 314.6 +/- 99.9 mg kg(-1) Cd in their aerial biomass, which was 5.7
      times greater than that in "78-04" tobacco (47.2 +/- 3.56 mg kg(-1)) (P <= 0.05).
      Two of these seedlings exceeded male parent P. frutescens in the Cd concentration
      of shoots and reached 424 and 396 mg kg(-1), which was 13% and 6% greater for
      that of perilla (374.2 +/- 10.38 mg kg(-1)), respectively. Compared with parents,
      two other F2 hybrids tended to accumulate more Cd in the root with
      bioconcentration factor (BCF) 7.05 and 5.17, respectively. Only one hybrid showed
      lower Cd concentration but transferred Cd more effectively from the root to the
      shoot than parents and other F2 hybrids, with the maximum translocation factor
      (TF) value 1.37. These indicated that the introduction of P. frutescens genes
      could obviously enhance the cadmium tolerance and accumulation of superior
      individuals.

PMID- 25567062
TI  - EPR and LC-MS studies on the mechanism of industrial dye decolorization by
      versatile peroxidase from Bjerkandera adusta.
AB  - The mechanisms of industrial dye transformation by versatile peroxidase were
      elucidated. Purified versatile peroxidase from Bjerkandera adusta was able to
      decolorize different classes of dyes including azo and phthalocyanines, but
      unable to transform any of the anthraquinones tested. Kinetic constants for
      selected dyes were determined and the transformation products were analyzed by
      EPR spectroscopy and mass spectrometry. The EPR and MS analyses of the enzymatic
      decolorization products showed the cleavage of the azo bond in azo dyes and the
      total disruption of the phthalocyaninic ring in phthalocyanine dyes. The EPR
      analysis on two copper-containing dyes, reactive violet 5 (azo) and reactive blue
      72 (phthalocyanine), showed that the transformation can or not break the metal
      ion coordination bond according the dye nature. The role of the catalytic Trp172
      in the dye transformation by a long-range electron transfer pathway was confirmed
      and the oxidation mechanisms are proposed and discussed. 

PMID- 25567063
TI  - Degradation of florfenicol in water by UV/Na2S 2O 8 process.
AB  - UV irradiation-activated sodium persulfate (UV/PS) was studied to degrade
      florfenicol (FLO), a phenicol antibiotic commonly used in aquaculture, in water.
      Compared with UV/H2O2 process, UV/PS process achieves a higher FLO degradation
      efficiency, greater mineralization, and less cost. The quantum yield for direct
      photolysis of FLO and the second-order rate constant of FLO with sulfate radicals
      were determined. The effects of various factors, namely PS concentration, anions
      (NO3 (-), Cl(-), and HCO3 (-)), ferrous ion, and humic acid (HA), on FLO
      degradation were investigated. The results showed that the pseudo-first-order
      rate constant increased linearly with increased PS concentration. The tested
      anions all adversely affected FLO degradation performance with the order of HCO3
      (-) > Cl(-) > NO3 (-). Coexisting ferrous ions enhanced FLO degradation at a
      Fe(2+)/PS molar ratio under 1:1. HA significantly inhibited FLO degradation due
      to radical scavenging and light-screening effect. Toxicity assessment showed that
      it is capable of controlling the toxicity for FLO degradation. These findings
      indicated that UV/PS is a promising technology for water polluted by antibiotics,
      and the treatment is optimized only after the impacts of water characteristics
      are carefully considered. 

PMID- 25567064
TI  - A matched-group study protocol to evaluate the implementation of an Integrated
      Care Pathway programme for chronic obstructive pulmonary disease in Singapore.
AB  - INTRODUCTION: The treatment of chronic obstructive pulmonary disease (COPD)
      involves different care providers across care sites. This fragmentation of care
      increases the morbidity and mortality burden, as well as acute health services
      use. The COPD-Integrated Care Pathway (ICP) was designed and implemented to
      integrate the care across different sites from primary care to acute hospital and
      home. It aims to reduce the prevalence of COPD among the population in the
      catchment, reduce risk of hospital admissions, delay or prevent the progression
      of the disease and reduce mortality rate by adopting a coordinated and
      multidisciplinary approach to the management of the patients' medical conditions.
      This study on the COPD-ICP programme is undertaken to determine the impact on
      processes of care, clinical outcomes and acute care utilisation. METHODS AND
      ANALYSIS: This will be a retrospective, pre-post, matched-groups study to
      evaluate the effectiveness of the COPD-ICP programme in improving clinical
      outcomes and reducing healthcare costs. Programme enrolees (intervention group)
      and non-enrolees (comparator group) will be matched using propensity scores.
      Administratively, we set 30% as our target for proportion admission difference
      between programme and non-programme patients. A sample size of 62 patients in
      each group will be needed for statistical comparisons to be made at 90% power.
      Adherence with recommended care elements will be measured at baseline and
      quarterly during 1-year follow-up. Risk of COPD-related hospitalisations as
      primary outcome, healthcare costs, disease progression and 1-year mortality
      during 1-year follow-up will be compared between the groups using generalised
      linear regression models. ETHICS AND DISSEMINATION: This protocol describes the
      implementation and proposed evaluation of the COPD-ICP programme. The described
      study has received ethical approval from the NHG Domain Specific Review Board
      (DSRB Ref: 2013/01200). Results of the study will be reported through peer-review
      publications and presentations at healthcare conferences.

PMID- 25567066
TI  - Neutron diffraction study of the (BiFeO3)1-x(PbTiO3)x solid solution:
      nanostructured multiferroic system.
AB  - Neutron diffraction studies performed on the solid solution of (BiFeO(3))(1
      x)(PbTiO(3))(x) reveal a mixture of two nanoscale phases with different crystal
      structures: a rhombohedral BiFeO(3)-based phase and a tetragonal PbTiO3-based
      phase. The ratio of Fe(3)+ and Ti(4)+ ions in the two phases is practically
      constant; only the proportion of the phases changes. The magnetic moments in the
      BiFeO(3)-based phase, in contrast to BiFeO(3), deviate from the basal plane. The
      temperature evolutions of the spin components along the hexagonal axis and within
      the perpendicular plane are different, leading to a spin re-orientation
      transition. The antiferromagnetic order in the PbTiO(3)-based phase corresponds
      to a simple structure with the propagation vector (1/2, 1/2, 1/2). The
      temperature dependence of the antiferromagnetic moment in the tetragonal phase at
      x = 0.5 indicates a canted antiferromagnetic order and a net ferromagnetic
      moment. A strong magnetic coupling between the two constituting phases due to the
      nanoscale character of the phases and well-developed interface between
      nanoparticles has been observed. The system of (BiFeO(3))(1-x)(PbTiO(3))(x)
      demonstrates an interesting scenario, where the proximity effects in the unstable
      system play a crucial role in the appearance of the unusual magnetic properties.

PMID- 25567065
TI  - Outcome following physician supervised prehospital resuscitation: a retrospective
      study.
AB  - BACKGROUND: Prehospital care provided by specially trained, physician-based
      emergency services (P-EMS) is an integrated part of the emergency medical systems
      in many developed countries. To what extent P-EMS increases survival and
      favourable outcomes is still unclear. The aim of the study was thus to
      investigate ambulance runs initially assigned 'life-saving missions' with
      emphasis on long-term outcome in patients treated by the Mobile Emergency Care
      Unit (MECU) in Odense, Denmark METHODS: All MECU runs are registered in a
      database by the attending physician, stating, among other parameters, the
      treatment given, outcome of the treatment and the patient's diagnosis. Over a
      period of 80 months from May 1 2006 to December 31 2012, all missions in which
      the outcome of the treatment was registered as 'life saving' were scrutinised.
      Initial outcome, level of competence of the caretaker and diagnosis of each
      patient were manually established in each case in a combined audit of the
      prehospital database, the discharge summary of the MECU and the medical records
      from the hospital. Outcome parameters were final outcome, the aetiology of the
      life-threatening condition and the level of competences necessary to treat the
      patient. RESULTS: Of 25 647 patients treated by the MECU, 701 (2.7%) received
      prehospital 'life saving treatment'. In 596 (2.3%) patients this treatment
      exceeded the competences of the attending emergency medical technician or
      paramedic. Of these patients, 225 (0.9%) were ultimately discharged to their own
      home. CONCLUSIONS: The present study demonstrates that anaesthesiologist
      administrated prehospital therapy increases the level of treatment modalities
      leading to an increased survival in relation to a prehospital system consisting
      of emergency medical technicians and paramedics alone and thus supports the
      concept of applying specialists in anaesthesiology in the prehospital setting
      especially when treating patients with cardiac arrest, patients in need of
      respiratory support and trauma patients.

PMID- 25567067
TI  - Home monitoring of implantable cardioverter-defibrillators: interpretation
      reliability of the second-generation "IEGM Online" system.
AB  - AIMS: Intracardiac electrograms (IEGMs) are essential for the assessment of
      implantable cardioverter-defibrillator (ICD) function. The Biotronik Home
      Monitoring systems transmit an 'IEGM Online' that is shorter than the full-length
      programmer IEGM due to technical constrains. The aim of this study was to
      evaluate the accuracy of the physician's classification of the underlying rhythm
      based on the second-generation IEGM Online. METHODS AND RESULTS: In total, 1533
      patients treated with single- and dual-chamber ICDs and cardiac resynchronization
      therapy defibrillators were enrolled at 67 investigational sites and followed for
      15 months. The investigators classified the rhythm shown in IEGM Online as
      ventricular tachycardia, ventricular fibrillation, atrial fibrillation, other
      supraventricular tachyarrhythmia, oversensing due to lead failure, T-wave
      oversensing, or other rhythm. At the next in-office follow-up, the investigators
      classified independently the rhythm seen in the corresponding programmer IEGM.
      The two rhythm classifications were compared thereafter. Both IEGM Online and
      programmer IEGM were available in 2099 arrhythmic or oversensing events, of which
      146 (7.0%) were classified as other rhythm or artefacts and were excluded as
      inconclusive or atypical. The remaining 1953 events, affecting 352 patients
      (23.0%), were classified correctly in 1803 cases (92.3%). The accuracy of rough
      rhythm classification as ventricular, supraventricular, or oversensing was 97.2%.
      CONCLUSION: The Lumax and IEGM Online HD Evaluation study demonstrates that
      remote IEGM analysis is reasonably accurate in a remote monitoring system that
      transmits shorter IEGM than the full-length programmer IEGM for the sake of
      frequent, fully automatic data transmission.

PMID- 25567068
TI  - Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation:
      results on health-related quality of life and symptom burden. The MANTRA-PAF
      trial.
AB  - AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in
      Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy
      of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug
      therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we
      evaluated the effect of these treatment modalities on the Health-Related Quality
      of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND
      RESULTS: During the study period, 294 patients were enrolled in the MANTRA-PAF
      trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic
      questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol
      five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in
      Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing
      during the trial. All comparisons were made on an intention-to-treat basis. Both
      randomization groups showed significant improvements in assessments with both SF
      36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly
      greater improvement in four physically related scales of the SF-36. The three
      most frequently reported symptoms were breathlessness during activity, pronounced
      tiredness, and worry/anxiety. In both groups, there was a significant reduction
      in ASTA symptom index and in the severity of seven of the eight symptoms over
      time. CONCLUSION: Both AAD and RFA as first-line treatment resulted in
      substantial improvement of HRQoL and symptom burden in patients with PAF.
      Patients randomized to RFA showed greater improvement in physical scales (SF-36)
      and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION: URL
      http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

PMID- 25567070
TI  - Selenite-induced toxicity in cancer cells is mediated by metabolic generation of
      endogenous selenium nanoparticles.
AB  - Selenite has been a touted cancer chemopreventative agent but generates
      conflicting outcomes. Multiple mechanisms of selenite cytotoxicity in cancer
      cells are thought to be induced by metabolites of selenite. We observed that
      intracellular metabolism of selenite generates endogenous selenium nanoparticles
      (SeNPs) in cancer cells. Critical proteins that bind with high affinity to
      elemental selenium during SeNPs self-assembly were identified through proteomics
      analysis; these include glycolytic enzymes, insoluble tubulin, and heat shock
      proteins 90 (HSP90). Sequestration of glycolytic enzymes by SeNPs dramatically
      inhibits ATP generation, which leads to functional and structural disruption of
      mitochondria. Transcriptome sequencing showed tremendous down-regulation of
      mitochondrial respiratory NADH dehydrogenase (complex I), cytochrome c oxidase
      (complex IV), and ATP synthase (complex V) in response to glycolysis-dependent
      mitochondrial dysfunction. Sequestration of insoluble tubulin led to microtubule
      depolymerization, altering microtubule dynamics. HSP90 sequestration led to
      degradation of its downstream effectors via autophagy, ultimately resulting in a
      cell-signaling switch to apoptosis. Additionally, the surface effects of SeNPs
      generated oxidative stress, thus contributing to selenite cytotoxicity. Herein,
      we reveal that the multiple mechanisms of selenite-induced cytotoxicity are
      caused by endogenous protein-assisted self-assembly of SeNPs and suggest that
      endogenous SeNPs could potentially be the primary cause of selenite-induced
      cytotoxicity. 

PMID- 25567069
TI  - Effects of Brazil nut consumption on selenium status and cognitive performance in
      older adults with mild cognitive impairment: a randomized controlled pilot trial.
AB  - PURPOSE: Oxidative stress is closely related to cognitive impairment, and the
      antioxidant system may be a potential therapeutic target to preserve cognitive
      function in older adults. Selenium plays an important antioxidant role through
      selenoproteins. This controlled trial aimed to investigate the antioxidant and
      cognitive effects of the consumption of Brazil nuts, the best selenium food
      source. METHODS: We enrolled 31 older adults with mild cognitive impairment (MCI)
      who were randomly assigned to ingestion of Brazil nuts or to the control group.
      Participants of the treatment group consumed one Brazil nut daily (estimated
      288.75 ug/day) for 6 months. Blood selenium concentrations, erythrocyte
      glutathione peroxidase (GPx) activity, oxygen radical absorbance capacity, and
      malondialdehyde were evaluated. Cognitive functions were assessed with the CERAD
      neuropsychological battery. RESULTS: Eleven participants of the treated group and
      nine of the control group completed the trial. The mean age of the participants
      was 77.7 (+/-5.3) years, 70 % of whom were female. We observed increased selenium
      levels after the intervention, whereas the control group presented no change.
      Among the parameters related to the antioxidant system, only erythrocyte GPx
      activity change was significantly different between the groups (p = 0.006). After
      6 months, improvements in verbal fluency (p = 0.007) and constructional praxis (p
      = 0.031) were significantly greater on the supplemented group when compared with
      the control group. CONCLUSION: Our results suggest that the intake of Brazil nut
      restores selenium deficiency and provides preliminary evidence that Brazil nut
      consumption can have positive effects on some cognitive functions of older adults
      with MCI.

PMID- 25567072
TI  - Gender Differences in Object of Desire Self-Consciousness Sexual Fantasies.
AB  - In a recent review article, Bogaert and Brotto (2014) discussed "object of desire
      self-consciousness," a perception that one is romantically and sexually desirable
      in another's eyes. They argued that this perception is more relevant to women's
      sociosexual functioning than it is to men's. In the present study, we attempted
      to find direct evidence that object of desire themes are linked more to women's
      sexual desire and arousal than they are to men's by examining the differences in
      content between men's and women's sexual fantasies. A total of 198 men and women
      reported on arousing themes in sexual fantasies using three methodologies:
      endorsement of items on a sexual fantasy questionnaire, sentence completion of
      sexually-charged scenarios, and open-ended sexual fantasies. The men and women
      also rated their attractiveness and were rated for attractiveness by two female
      experimenters. On all three fantasy composites, women endorsed more object of
      desire themes than did men, and these effects occurred independent of the
      subjective and observer-rated attractiveness measures. The results were discussed
      in relation to theorizing that object of desire self-consciousness can function
      as part of many women's self-schemata or scripts related to romance and
      sexuality. 

PMID- 25567073
TI  - Women's motivations to have sex in casual and committed relationships with male
      and female partners.
AB  - Women report a wide variety of reasons to have sex (e.g., Meston & Buss, 2010),
      and while it is reasonable to assume that those reasons may vary based on the
      context of the relationship, this assumption has not yet been tested. The purpose
      of this study was to explore how relationship type, sexual attraction, and the
      gender of one's partner interact and affect the sexual motivations of women. A
      total of 510 women (361 who reported exclusively other-sex attraction and 149 who
      reported same-sex/bisexual attraction) completed the YSEX? questionnaire.
      Participants rated their sexual motivations for casual sex and sex in a committed
      relationship with male and/or female partners, depending on reported sexual
      attraction. Results showed that relationship type affected reported motivation
      for sex: physical motivations were more strongly endorsed for casual sex, whereas
      emotional motivations were more strongly endorsed for sex in committed
      relationships. No significant differences in motivation were reported between
      women who reported same-sex attraction and those who did not. Women who reported
      bisexual attraction and identified as being lesbian, bisexual, or another sexual
      minority reported no significant differences in motivation for sex with male or
      female partners. The results of this study highlight the importance of
      relationship context when discussing sexual motivation and suggest a high degree
      of similarity in motivation for women, regardless of sexual orientation or gender
      of partner.

PMID- 25567071
TI  - "Nothing Is Free": A Qualitative Study of Sex Trading Among Methamphetamine Users
      in Cape Town, South Africa.
AB  - South Africa is facing an established epidemic of methamphetamine, known locally
      as "tik." Globally, methamphetamine has been linked to high rates of sexual risk
      behaviors, including sex trading. The goal of this study was to qualitatively
      examine the experiences of sex trading among methamphetamine users in Cape Town,
      South Africa. Individual in-depth interviews were conducted with 30 active
      methamphetamine users (17 men and 13 women) recruited from the community.
      Interviews were conducted in local languages using a semi-structured guide that
      included questions on sex trading experiences and perceptions of sex trading
      among methamphetamine users. Interviews were audio-recorded, transcribed, and
      analyzed using analytic memos and coding with constant comparison techniques. The
      data revealed that in a setting of high levels of addiction and poverty, sex was
      an important commodity for acquiring methamphetamine. Women were more likely to
      use sex to acquire methamphetamine, but men reported opportunistic cases of
      trading sex for methamphetamine. Four models of sex trading emerged: negotiated
      exchange, implicit exchange, relationships based on resources, and facilitating
      sex exchange for others. The expectation of sex trading created a context in
      which sexual violence against female methamphetamine users was common. Multiple
      sexual partners and inconsistent condom use in acts of sex trading put
      methamphetamine users at high risk of HIV. Interventions in this setting should
      address addiction, which is the primary driver of sex trading among
      methamphetamine users. Harm reduction interventions may include education about
      HIV and other sexually transmitted infections, availability of condoms and HIV
      testing, and sexual violence prevention. 

PMID- 25567074
TI  - Meeting sex partners through the Internet, risky sexual behavior, and HIV testing
      among sexually transmitted infections clinic patients.
AB  - The Internet has now become a popular venue to meet sex partners. People who use
      the Internet to meet sex partners may be at a higher risk for contracting HIV and
      STIs. This study examined the association between meeting sex partners from the
      Internet, and HIV testing, STI history, and risky sexual behavior. Data were
      obtained from the Virginia Department of Health STD Surveillance Network.
      Logistic regression models were used to obtain crude and adjusted odds ratios,
      and 95 % confidence intervals for the associations between meeting sex partners
      through the Internet and ever tested for HIV, HIV testing in the past 12 months,
      STI history, and risky sexual behavior. Logistic regression was also used to
      determine if gender and men who have sex with men interaction terms significantly
      improved the model. Women who met a sex partner from the Internet were more
      likely to have had an HIV test in the past 12 months than women who did not meet
      a partner in this way. On the other hand, men who met a sex partner through the
      Internet were more likely to have ever had an HIV test than other men, but this
      was only seen for heterosexual men. All populations who met a sex partner from
      the Internet were more likely to take part in risky sexual behavior. HIV
      prevention strategies should emphasize annual testing for all populations. 

PMID- 25567075
TI  - Mapping 'consistency' in India's climate change position: Dynamics and dilemmas
      of science diplomacy.
AB  - India's position on climate change negotiations is likely to have far reaching
      implications for the success of global climate cooperation. Since the beginning
      of negotiations, the principle of equity and common but differentiated
      responsibilities (CBDR) remained the centerpiece of India's stand. The stand
      started to evolve at the 15th Conference of Parties to the United Nations
      Framework Convention on Climate Change at Copenhagen in 2009, when India accepted
      voluntary commitments to reduce emission intensity. Though India still swears by
      CBDR, status of the principle in the negotiations has become doubtful after the
      Durban Climate Conference in 2011 committed all parties to take emission targets.
      This paper traces major transition points in India's negotiating position over
      the years and provides a descriptive context of its climate-related concerns. It
      analyzes the interview responses of 15 top scientists, experts, and negotiators
      to build upon core areas of climate change issues in India, its future role, and
      position in negotiations. Interviewees, in general, were in favor of protecting
      the carbon space for the poor who had very low emissions. 

PMID- 25567076
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in
      mediastinal lymphadenopathy.
AB  - Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) is
      accepted as a safe and minimally invasive modality for evaluation of mediastinal
      pathologies in adults. There is scanty literature on the utilization and
      performance characteristics of Convex probe EBUS-TBNA in children. The authors
      herein describe two pediatric patients with mediastinal lymphadenopathy wherein
      the underlying diagnosis was unclear based on the clinico-radiological profile. A
      possibility of lymphoma was considered in one of the patients. EBUS-TBNA was
      performed for obtaining tissue samples from the enlarged mediastinal lymph nodes
      and diagnosis of tuberculosis was established in both the patients. The authors
      review the available literature on Pediatric EBUS TBNA. EBUS-TBNA is an exciting
      and promising approach towards safe and accurate evaluation of mediastinal
      pathologies in children. Pediatric EBUS-TBNA needs further evaluation in
      prospective studies. 

PMID- 25567077
TI  - Outcome of surgical treatment of primary aldosteronism.
AB  - PURPOSE: The aim of this retrospective study was to analyze the early and long
      term outcomes of the surgical treatment of primary aldosteronism (PA), the most
      common surgically correctable cause of endocrine hypertension. METHODS: Serum
      Potassium levels, blood pressure values, and aldosterone/renin ratio (ARR) were
      assessed in 128 patients undergoing unilateral adrenalectomy for PA, before and
      after surgery. The role of lateralizing techniques and the relationship between
      outcome and histopathology findings were also evaluated. RESULTS: Biochemical
      cure of PA (ARR and kalemia normalization) was achieved in 95 % of patients, at
      early follow-up. Single aldosterone-producing adenoma, multinodular hyperplasia,
      and diffuse hyperplasia were found in 46, 45, and 9 % of the patients,
      respectively. No relationship between histopathology and persistence or
      recurrence of PA was found. The use of further lateralizing techniques in
      addition to computed tomography or magnetic resonance was the main predictor of
      PA cure (p = 0.02); adrenal venous sampling (AVS) was more accurate than
      scintigraphy in PA lateralization (p < 0.05). After surgery, hypertension was
      cured in 55 % and improved in 36 % of patients. Female gender, a lower number of
      antihypertensive drugs, and a shorter duration of hypertension were the main
      predictors of hypertension cure. At long-term, recurrent PA occurred in 3.7 % of
      cases. CONCLUSIONS: Early diagnosis and correct lateralization of
      hyperaldosteronism by means of AVS are keys to achieve surgical cure of PA and PA
      related hypertension. PA may be also caused by unilateral hyperplasia, which may
      be cured by unilateral adrenalectomy. Recurrences of PA are rare, although a
      prolonged follow-up is required.

PMID- 25567078
TI  - Effects of advanced maternal age and race/ethnicity on placental weight and
      placental weight/birthweight ratio in very low birthweight infants.
AB  - To study the association of advanced maternal age (AMA) and race/ethnicity on
      placental pathology in very low birthweight (VLBW) infants. Retrospective
      analysis of placental pathology of inborn singleton VLBW infants from a regional
      level 3 NICU between July, 2002 and June, 2009. Subjects were stratified by age
      and race/ethnicity. Statistical analysis included One-way ANOVA, Chi Square and
      multivariable analyses. A total of 739 mother/infant dyads were included. AMA was
      associated with a decrease in placental weight and placental weight/birthweight
      ratio. Black/Non-Hispanic mothers >=35 had a lower placental weight (p = 0.01)
      and lower placental weight/birth weight ratio (z-score, -0.45 +/- 0.71 vs -0.04
      +/- 1.1, p = 0.01) compared to Black/Non-Hispanic mothers <35 years of age. After
      controlling for gestational age, race/ethnicity, maternal diabetes, maternal
      smoking, maternal hypertension and clinical chorioamnionitis, AMA, but not
      race/ethnicity, remained independently associated with placental
      weight/birthweight ratio z score (full model r(2) = 0.22, p < 0.01). In our study
      sample of VLBW infants, placental weight and placental weight/birthweight ratio
      were lower in mothers of advanced maternal age compared to mothers <35 years of
      age. Our data suggest that maternal age affects placentation in VLBW infants,
      which could influence maternal and neonatal outcomes.

PMID- 25567079
TI  - Brain surface reformatted imaging (BSRI) for intraoperative neuronavigation in
      brain tumor surgery.
AB  - BACKGROUND: For safe resection of lesions situated in or near eloquent brain
      regions, determination of their spatial and functional relationship is crucial.
      Since functional magnetic resonance imaging and intraoperative neurophysiological
      mapping are not available in all neurosurgical departments, we aimed to evaluate
      brain surface reformatted imaging (BSRI) as an additional display mode for
      neuronavigation. METHODS: Eight patients suffering from perirolandic tumors were
      preoperatively studied with MRI and navigated transcranial magnetic stimulation
      (nTMS). Afterwards, the MRI was automatically transformed into BSR images in
      neuronavigation software (Brainlab, Brainlab AG, Feldkirchen, Germany). One
      experienced neuroradiologist, one experienced neurosurgeon, and two residents
      determined hand representation areas ipsilateral to each tumor on two-dimensional
      (2D) MR images and on BSR images. All results were compared to results from
      intraoperative direct cortical mapping of the hand motor cortex and to
      preoperative nTMS results. RESULTS: Findings from nTMS and intraoperative direct
      cortical mapping of the hand motor cortex were congruent in all cases. Hand
      representation areas were correctly determined on BSR images in 81.3 % and on 2D
      MR images in 93.75 % (p = 0.26). In a subgroup analysis, experienced observers
      showed more familiarity with BSRI than residents (96.9 vs. 84.4 % correct
      results, p = 0.19), with an equal error rate for 2D-MRI. The time required to
      define hand representation areas was significantly shorter using BSRI than using
      standard MRI (mean 27.4 vs. 40.4 s, p = 0.04). CONCLUSIONS: With BSRI, a new
      method for neuronavigation is now available, allowing fast and easy
      intraoperative localization of distinct brain regions.

PMID- 25567081
TI  - Abnormalities of vestibular-evoked myogenic potentials in idiopathic Parkinson's
      disease are associated with clinical evidence of brainstem involvement.
AB  - Brainstem degeneration in Parkinson's disease (PD) may explain the occurrence of
      many non-motor symptoms in this condition. Purposes of the present work were to
      investigate brainstem function in PD through a battery of vestibular-evoked
      myogenic potentials (VEMP) allowing a comprehensive brainstem exploration and to
      correlate VEMP findings with symptoms related to brainstem involvement. Cervical
      (cVEMP), masseter (mVEMP) and ocular (oVEMP) VEMPs were investigated in 24 PD
      patients and compared with those recorded in 24 age-matched controls. Presence of
      symptoms ascribable to brainstem dysfunction, such as daytime sleepiness, REM
      sleep behavior disorder and depression, was investigated through Epworth
      Sleepiness Scale, Parkinson's Disease Sleep Scale, REM Sleep Disorder Screening
      Questionnaire (RBD-SQ) and Geriatric Depression Scale. Postural instability was
      additionally assessed through mini-BESTest. The frequency of alteration of VEMPs
      in patients was 83.3 % when considering the whole set and 41.7 % for cVEMP, 66.7
      % for mVEMP and 45.8 % for oVEMP. This was significantly different from controls,
      with absence being the prevalent alteration in PD. A significant inverse
      correlation between the number of altered VEMPs and mini-BESTest and a direct
      correlation with RBD-SQ were found. The VEMP battery under study allowed the
      identification of brainstem dysfunctions in PD patients, which correlated with
      clinical tests suggestive of postural and REM sleep disorders. VEMPs might
      represent a valuable tool of brainstem assessment in PD.

PMID- 25567080
TI  - The Italian Registry of Endovascular Treatment in Acute Stroke: rationale, design
      and baseline features of patients.
AB  - Endovascular treatment (ET) showed to be safe in acute stroke, but its
      superiority over intravenous thrombolysis is debated. As ET is rapidly evolving,
      it is not clear which role it may deserve in the future of stoke treatments.
      Based on an observational design, a treatment registry allows to study a broad
      range of patients, turning into a powerful tool for patients' selection. We
      report the methodology and a descriptive analysis of patients from a national
      registry of ET for stroke. The Italian Registry of Endovascular Treatment in
      Acute Stroke is a multicenter, observational registry running in Italy from 2010.
      All patients treated with ET in the participating centers were consecutively
      recorded. Safety measures were symptomatic intracranial hemorrhage, procedural
      adverse events and death rate. Efficacy measures were arterial recanalization and
      3-month good functional outcome. From 2008 to 2012, 960 patients were treated in
      25 centers. Median age was 67 years, male gender 57 %. Median baseline NIHSS was
      17. The most frequent occlusion site was Middle cerebral artery (46.9 %). Intra
      arterial thrombolytics were used in 165 (17.9 %) patients, in 531 (57.5 %)
      thrombectomy was employed, and 228 (24.7 %) patients received both treatments.
      Baseline features of this cohort are in line with data from large clinical series
      and recent trials. This registry allows to collect data from a real practice
      scenario and to highlight time trends in treatment modalities. It can address
      unsolved safety and efficacy issues on ET of stroke, providing a useful tool for
      the planning of new trials.

PMID- 25567082
TI  - Forgetful and robotic: tap on a gene!

PMID- 25567084
TI  - Structural, transport and optical properties of (La0.6Pr0.4)0.65Ca0.35MnO3
      nanocrystals: a wide band-gap magnetic semiconductor.
AB  - (La0.6Pr0.4)0.65Ca0.35MnO3 system has been synthesized via a sol-gel route at
      different sintering temperatures. Structural, transport and optical measurements
      have been carried out to investigate (La0.6Pr0.4)0.65Ca0.35MnO3 nanoparticles.
      Raman spectra show that Jahn-Teller distortion has been decreased due to the
      presence of Ca and Pr in A-site. Magnetic measurements provide a Curie
      temperature around 200 K and saturation magnetization (MS) of about 3.43MUB/Mn at
      5 K. X-ray photoemission spectroscopy study suggests that Mn exists in a dual
      oxidation state (Mn(3+) and Mn(4+)). Resistivity measurements suggest that charge
      ordered states of Mn(3+) and Mn(4+), which might be influenced by the presence of
      Pr, have enhanced insulating behavior in (La0.6Pr0.4)0.65Ca0.35MnO3. Band gap
      estimated from UV-Vis spectroscopy measurements comes in the range of wide band
      gap semiconductors (~3.5 eV); this makes (La0.6Pr0.4)0.65Ca0.35MnO3 a potential
      candidate for device application. 

PMID- 25567083
TI  - Liquid Chromatography-Tandem Mass Spectrometry Screening Method for the Detection
      of Radical-Scavenging Natural Antioxidants from the Whole Scutellariae (Radix,
      Stem and Leaf).
AB  - A novel free radical reaction combined with high-performance LC-photodiode array
      ESI-MS/MS screening method was developed for the detection and identification of
      natural antioxidants from whole Scutellariae. Six compounds and whole
      Scutellariae extracts were found to possess a potential antioxidant capacity, and
      their free radical-scavenging activities were investigated in detail. The six
      compounds were identified as baicalin, baicalein, scutellarin, scutellarein,
      wogonoside and chrystin-7-glucoronide. The present study reveals that the radical
      scavenging capacities of the whole Scutellariae extracts are as follows: hydroxyl
      radical > superoxide radical > peroxy radical. Wogonoside showed the strongest
      capability for scavenging hydroxyl radical. Baicalein not only showed the
      strongest capability for scavenging superoxide radical but also showed capability
      for lipid radical; Scutellarein (Peak 5) exhibited the highest reactivity in the
      lipid peroxidation processes. Based on these studies, the current paper
      accomplishes the evaluation of activities of some important anti-radical
      substances extracted from the radix, stem and leaf of the whole Scutellariae. 

PMID- 25567085
TI  - Modulation of intrinsic and reflexive contributions to low-back stabilization due
      to vision, task instruction, and perturbation bandwidth.
AB  - The goal of this study is to assess how reflexes and intrinsic properties
      contribute to low-back stabilization and modulate with conditions. Upper body
      sway was evoked by anterior-posterior platform translations, while subjects were
      seated with a restrained pelvis and free upper body. Kinematic analysis of trunk
      translations and rotations illustrated that a fixed rotation point between the
      vertebrae L4 and L5 adequately captures lumbar bending up to 5 Hz. To investigate
      the motor control modulation, the conditions varied in vision (eyes open or
      closed), task instruction (Balance naturally or Resist perturbations by
      minimizing low-back motions), and perturbation bandwidth (from 0.2 up to 1, 3 or
      10 Hz). Frequency response functions and physiological modeling parameters showed
      substantial modulation between all conditions. The eyes-open condition led to
      trunk-in-space behavior with additional long-latency visual feedback and
      decreased proprioceptive feedback. The task instruction to resist led to trunk-on
      pelvis stabilization behavior, which was achieved by higher co-contraction levels
      and increased reflexive velocity feedback. Perturbations below the low-back
      natural frequency (~1 Hz) led to trunk-on-pelvis stabilization behavior, mainly
      attributed to increased intrinsic damping. This indicates that bandwidth effects
      should not be ignored and that experiments with high-bandwidth perturbations do
      not fully represent the intrinsic and reflexive behavior during most (low
      bandwidth) daily life activities. The neck stabilized the head orientation
      effectively (head rotation amplitudes 2 % of trunk), but did not effectively
      stabilize the head in space (global head translations exceeded trunk translations
      by 20 %). This indicates that low-back motor control is involved in head-in-space
      stabilization and could explain the low-back motor control modulations due to
      vision.

PMID- 25567086
TI  - The neural basis of implicit learning of task-irrelevant Chinese tonal sequence.
AB  - The present study sought to investigate the neural basis of implicit learning of
      task-irrelevant perceptual sequence. A novel SRT task, the serial syllable
      identification task (SSI task), was used in which the participants were asked to
      recognize which one of two Chinese syllables was presented. The tones of the
      syllables were irrelevant to the task but followed an underlying structured
      sequence. Participants were scanned while they performed the SSI task. Results
      showed that, at the behavioral level, faster RTs for the sequential material
      indicated that task-irrelevant sequence knowledge could be learned. In the
      subsequent prediction test of knowledge of the tonal cues using subjective
      measures, we found that the knowledge was obtained unconsciously. At the neural
      level, the left caudate, bilateral hippocampus and bilateral superior parietal
      lobule were engaged during the sequence condition relative to the random
      condition. Further analyses revealed that greater learning-related activation
      (relative to random) in the right caudate nucleus, bilateral hippocampus and left
      superior parietal lobule were found during the second half of the training phase
      compared with the first half. When people reported that they were guessing, the
      magnitude of the right hippocampus and left superior parietal lobule activations
      was positively related to the accuracy of prediction test, which was
      significantly better than chance. Together, the present results indicated that
      the caudate, hippocampus and superior parietal lobule played critical roles in
      the implicit perceptual sequence learning even when the perceptual features were
      task irrelevant. 

PMID- 25567087
TI  - Differential changes in gingival somatosensory sensitivity after painful
      electrical tooth stimulation.
AB  - We aimed to evaluate the effect of painful tooth stimulation on gingival
      somatosensory sensitivity of healthy volunteers in a randomized, controlled
      design. Thirteen healthy volunteers (six women, seven men; 28.4 +/- 5.0 years)
      were included for two experimental sessions of electrical tooth stimulation:
      painful tooth stimulation and tooth stimulation below the sensory threshold
      (control). Eight of the human subjects participated in a third session without
      tooth stimulation. In all sessions, the somatosensory sensitivity of the gingiva
      adjacent to the stimulated tooth was evaluated with a standardized battery of
      quantitative sensory tests (QST) before, immediately after and 30 min after tooth
      stimulation. Painful tooth stimulation evoked significant decreases in warmth and
      heat pain thresholds (P < 0.001) as well as pressure pain thresholds (increased
      sensitivity) (P = 0.024) and increases in mechanical detection thresholds
      (decreased sensitivity) (P < 0.050). Similar thermal threshold changes (P <
      0.019) but no mechanical changes were found after tooth stimulation below the
      sensory threshold (P > 0.086). No QST changes were detected in the session
      without tooth stimulation (P > 0.060). In conclusion, modest increased gingival
      sensitivity to warmth, painful heat and pressure stimuli as well as
      desensitization to non-painful mechanical stimulation were demonstrated after
      tooth stimulation. This suggests involvement of competing heterotopic
      facilitatory and inhibitory mechanisms. Furthermore, stimulation below the
      sensory threshold induced similar thermal sensitization suggesting the
      possibility of activation of axon-reflex-like mechanisms even at intensities
      below the perception threshold. These findings may have implications for
      interpretation of somatosensory results in patients with chronic intraoral pain.

PMID- 25567088
TI  - The prevalence effect in lateral masking and its relevance for visual search.
AB  - In stimulus displays with or without a single target amid 1,644 identical
      distractors, target prevalence was varied between 20, 50 and 80 %. Maximum gaze
      deviation was measured to determine the strength of lateral masking in these
      arrays. The results show that lateral masking was strongest in the 20 %
      prevalence condition, which differed significantly from both the 50 and 80 %
      prevalence conditions. No difference was observed between the latter two. This
      pattern of results corresponds to that found in the literature on the prevalence
      effect in visual search (stronger lateral masking corresponding to longer search
      times). The data add to similar findings reported earlier (Wertheim et al. in Exp
      Brain Res, 170:387-402, 2006), according to which the effects of many well-known
      factors in visual search correspond to those on lateral masking. These were the
      effects of set size, disjunctions versus conjunctions, display area, distractor
      density, the asymmetry effect (Q vs. O's) and viewing distance. The present data,
      taken together with those earlier findings, may lend credit to a causal
      hypothesis that lateral masking could be a more important mechanism in visual
      search than usually assumed.

PMID- 25567089
TI  - Distracting visuospatial attention while approaching an obstacle reduces the toe
      obstacle clearance.
AB  - Obstacle crossing during walking requires visuospatial attention to identify the
      obstacle, so that individuals can integrate visual and somatosensory information
      for raising the foot with appropriate height and timing without being tripped.
      However, the interaction between control of foot trajectory and orientation of
      visuospatial attention during obstacle crossing is complicated and remains
      unclear. This study probed where attention is directed when approaching and
      stepping over an obstacle during gait and examined how the presence of the
      obstacle affects the distribution of attention during walking. Eleven young
      healthy adults performed a visuospatial attention task while standing (Stand),
      crossing over an obstacle placed either before (ObsBefore) or after (ObsAfter)
      the visual target, or crossing without the visual target (ObsOnly). Toe-obstacle
      clearance was reduced for the trailing leg in the ObsAfter condition but remained
      the same for the ObsBefore and ObsOnly conditions. In addition, the accuracy rate
      of the visuospatial attention task tended to be higher at the locations closer to
      the obstacle. Taken together, these results demonstrate that visuospatial
      attention and the processes underlying obstacle crossing during locomotion
      interact in both a spatially and temporally dependent manner.

PMID- 25567090
TI  - Impaired visuomotor adaptation in adults with ADHD.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a prevalent psychiatric
      disorder in children that often continues into adulthood. It has been suggested
      that motor impairments in ADHD are associated with underlying cerebellar
      pathology. If such is the case, individuals with ADHD should be impaired on motor
      tasks requiring healthy cerebellar function. To test this, we compared
      performance of individuals with ADHD and ADHD-like symptoms with non-ADHD
      controls on a visuomotor adaptation task known to be impaired following
      cerebellar lesions. Participants adapted reaching movements to a visual
      representation that was rotated by 30 degrees . Individuals with ADHD and those
      with ADHD-like symptoms took longer to correct the angle of movement once the
      rotation was applied relative to controls. However, post-adaptation residual
      effect did not differ for individuals with ADHD and ADHD-like symptoms compared
      to the control group. These results are consistent with the hypothesis that mild
      cerebellar deficits are evident in the motor performance of adults with ADHD.

PMID- 25567091
TI  - Effector mass and trajectory optimization in the online regulation of goal
      directed movement.
AB  - Goal-directed aiming movements are planned and executed so that they optimize
      speed, accuracy and energy expenditure. In particular, the primary submovements
      involved in manual aiming attempts typically undershoot targets in order to avoid
      costly time and energy overshoot errors. Furthermore, in aiming movements
      performed over a series of trials, the movement planning process considers the
      sensory information associated with the most recent aiming attempt. The goal of
      the current study was to gain further insight into how the sensory consequences
      associated with the recent and forthcoming aiming attempts impact performance. We
      first examined whether performers are more conservative in their aiming movements
      with a heavy, as opposed to a light, stylus by determining whether primary
      submovements undershot the target to a greater extent in the former due to an
      anticipated increase in spatial variability. Our results show that movements with
      the heavy stylus demonstrated greater undershoot biases in the primary
      submovements, as well as greater trial-to-trial spatial variability at specific
      trajectory kinematic landmarks. In addition, we also sought to determine whether
      the sensory information experienced on a previous aiming movement affected
      movement planning and/or online control on the subsequent aiming attempt. To vary
      the type sensory consequences experienced on a trial-to-trial basis, participants
      performed aiming movements with light and heavy styli in either blocked or random
      orderings of trials. In the random-order conditions, some participants were
      provided advance information about stylus mass for the upcoming trial, while
      others were not. The blocked and random trial orders had minimal impacts on end
      point aiming performance. Furthermore, similarities in the times to key kinematic
      landmarks in the trajectories of the random-order groups suggest that recent
      trial experience had a greater effect on the upcoming aiming movement compared
      with advance task knowledge. 

PMID- 25567094
TI  - Wildlife use and the role of taboos in the conservation of wildlife around the
      Nkwende Hills Forest Reserve; South-west Cameroon.
AB  - BACKGROUND: Cameroon is known as Africa in miniature because of its multitude of
      ecosystems and associated biodiversity, cultures and traditions. The country also
      harbors very ancient human populations whose relationship with nature is very
      intimate and where animals play important roles for their livelihood. Located in
      the South-west region of Cameroon, the Nkwende Hills Forest Reserve (NHFR)
      represents an important wildlife conservation site because of its strategic
      position at the periphery of Korup National Park (KNP). The periphery of NHFR is
      inhabited by several ethnic groups amongst which are the Obang and Ngunnchang
      clans who share particular relationships with wildlife. The present paper studies
      these relationships and contributes to the growing trend of scientific
      ethnozoological studies across Africa. METHOD: From August to December 2011, a
      questionnaire survey was addressed to 126 randomly chosen household respondents
      (HRs) in seven villages at the Northwest periphery of NHFR. In households,
      preference was given to parents, and to the eldest child in case the parents were
      absent. Questions related to the uses and local taboos on wildlife species were
      asked to HRs. RESULTS: Both communities have accumulated knowledge on the use of
      51 wildlife species of which 50.9% represent mammals, 21.6% birds, 15.7%
      reptiles, 7.8% fish and 3.9% invertebrates. Four main use categories of wildlife
      by both communities were identified, namely (1) Food, medicine and sales values
      (41.2%), (2) Ethnomusical animals and parts used as trophy (29.2%), (3)
      Decoration and jewelry making values (21.9%) and (4) Magico-religious and
      multipurpose values (7.8%). Regarding local taboos, species specific taboos
      (generation totems and acquired totems), habitat taboos (sacred forests), method
      and segment taboos still persist but are rarely respected among the youth mainly
      because of the scarcity of wildlife (65.3% of HRs). CONCLUSION: Like other
      communities living around forest areas, the studied communities use wildlife in
      their culture and tradition. Wildlife is not only used for consumption, but also
      for traditional medicines, craft materials and spiritual purposes. But, threats
      to wildlife and their traditional uses are real and acculturation seems to be the
      main driver. High priority should be given to the reconciling conservation of
      species with high values for local communities and human needs.

PMID- 25567093
TI  - A norovirus oyster-related outbreak in a nursing home in France, January 2012.
AB  - The presence of norovirus in shellfish is a public health concern in Europe.
      Here, we report the results of an investigation into a norovirus gastroenteritis
      outbreak following a festive lunch which affected 84 (57%) residents and staff
      members of a nursing home in January 2012 in France. Individuals who had eaten
      oysters had a significantly higher risk of developing symptoms in the following
      2.5 days than those who had not, the risk increasing with the amount eaten
      [relative risk 2.2 (1.0-4.6) and 3.3 (1.6-6.6) for 3-4 and 5-12 oysters,
      respectively]. In healthy individuals during those days, 29 (32%) subsequently
      became ill, most of whom were staff members performing activities in close
      contact with residents. Genogroup II noroviruses were detected in faecal samples,
      in a sample of uneaten oysters and in oysters from the production area.
      Identifying a norovirus's infectious dose may facilitate the health-related
      management of contaminated shellfish. 

PMID- 25567092
TI  - How does high-frequency sound or vibration activate vestibular receptors?
AB  - The mechanism by which vestibular neural phase locking occurs and how it relates
      to classical otolith mechanics is unclear. Here, we put forward the hypothesis
      that sound and vibration both cause fluid pressure waves in the inner ear and
      that it is these pressure waves which displace the hair bundles on vestibular
      receptor hair cells and result in activation of type I receptor hair cells and
      phase locking of the action potentials in the irregular vestibular afferents,
      which synapse on type I receptors. This idea has been suggested since the early
      neural recordings and recent results give it greater credibility.

PMID- 25567095
TI  - The impact of four family support programmes for people with a disability in
      Ireland.
AB  - BACKGROUND: This article reports on an evaluation of four family support
      programmes in Ireland for families of people with a physical or an intellectual
      disability or autism. The focus of the evaluation, which took place within a year
      of the programmes' completion, was on establishing whether the programmes had an
      impact on families' capacity to effectively support their family member. METHOD:
      A mixed-method design was used, which included a survey (n = 38) and interviews
      (n = 19) with participating family members. Ethical approval for the study was
      given by the relevant university ethics committee. RESULTS: Findings suggest that
      participation in the programmes enhanced knowledge, attitudes, and competencies
      of families and also impacted their ability to advocate for their family member
      and to connect with the community. DISCUSSION AND CONCLUSIONS: Whilst outcomes
      were overwhelmingly positive, further follow-up would be required to ascertain if
      sustained capacity building took place.

PMID- 25567096
TI  - Postsecondary inclusion for individuals with an intellectual disability and its
      effects on employment.
AB  - Postsecondary education (PSE) programs for individuals with intellectual
      disabilities (IDs) have emerged exponentially in the United States over the last
      decade. Research regarding these postsecondary programs has largely been
      descriptive, and thus, there exists a need for qualitative, outcome-based
      research. In this comparative case report, graduates from two types of PSE
      programs for individuals with IDs are surveyed regarding employment outcomes and
      other personal developments. The results from each postsecondary program are
      compared with one another and also with a comparison group of individuals with
      IDs who did not attend a postsecondary program (utilizing the 2009 National
      Longitudinal Transition Study 2). This case demonstrates significant positive
      employment outcomes for individuals with IDs who attend postsecondary programs
      compared to those who do not attend such programs and highlights similarities and
      differences regarding outcomes of the two program types under consideration. 

PMID- 25567097
TI  - Psychosocial experiences of chronic illness in individuals with an intellectual
      disability: A systematic review of the literature.
AB  - BACKGROUND: Increased life expectancy has led to an increase in diagnoses of
      chronic illness in people with an intellectual disability; despite this increase,
      research about the psychological impact is rare. This review explored the
      psychosocial experiences of chronic illness in adults with an intellectual
      disability, revealing potential predictors and moderators of these experiences.
      METHODS: Online databases were systematically searched to identify relevant
      literature, using predefined inclusion criteria. Of the 25,058 titles initially
      identified, 4 were included, that is, those collecting data on people with an
      intellectual disability and diagnosed with cancer (n = 2), chronic pain (n = 1)
      and diabetes (n = 1). RESULTS: Narrative synthesis of the data identified six
      themes, namely, (1) delayed diagnosis, (2) information, communication and
      understanding, (3) negative psychological consequences, (4) negative physical
      consequences, (5) social perception and (6) social support. CONCLUSIONS: There
      are unmet needs within this population, including a lack of assistance in
      understanding their illness. A substantial gap in the literature should be
      addressed through further empirical work.

PMID- 25567100
TI  - Structure-guided design and biosynthesis of a novel FR-900098 analogue as a
      potent Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase
      (Dxr) inhibitor.
AB  - We report here the enzymatic biosynthesis of FR-900098 analogues and establish an
      in vivo platform for the biosynthesis of an N-propionyl derivative FR-900098P. FR
      900098P is found to be a significantly more potent inhibitor of Plasmodium
      falciparum 1-deoxy-D-xylulose 5-phosphate reductoisomerase (PfDxr) than the
      parent compound, and thus a more promising antimalarial drug candidate.

PMID- 25567101
TI  - Classification of the renal vein variations: a study with multidetector computed
      tomography.
AB  - PURPOSE: To estimate the incidence, anatomical feature as well as type of the
      renal vein variation with multidetector computed tomography (MDCT) in an adult
      population. METHODS: A total of 1,452 patients who underwent MDCT angiography
      were retrospectively evaluated for the presence (number, length, origination,
      destination, branching pattern and course) of the renal vein variation. chi2 test
      was used to compare the incidence of variations in left and right renal veins and
      the incidence of variations in each side renal vein between males and females.
      RESULTS: Renal vein variations were observed in 358 patients (24.7 %, 358/1,452),
      which included 103 patients (7.1 %, 103/1,452) with left renal vein (LRV)
      variations, 279 patients (19.2 %, 279/1,452) with right renal vein (RRV)
      variations and 24 patients (1.7 %, 24/1,452) with bilateral renal vein
      variations. The frequency of RRV variations was significantly higher than that of
      LRV variations (p < 0.05). No statistically significant correlation was found
      between variations of renal vein (LRV and RRV) and gender (p > 0.05). According
      to the morphology of the renal vein, we classified LRV variations into five
      types: type I, circumaortic LRV (2.1 %, 31/1,452); type II, retroaortic LRV (2.1
      %, 30/1,452); type III, abnormal reflux (1.7 %, 24/1,452); type IV, late venous
      confluence of LRV (0.9 %, 13/1,452); type V, rare type (0.3 %, 5/1,452), and RRV
      variations into three types: type 1, additional renal vein (18.7 %, 271/1,452);
      type 2, abnormal reflux (0.4 %, 6/1,452); type 3, rare type (0.1 %, 2/1,452).
      CONCLUSION: The renal vein variations are not unusual, particularly in the RRV.
      Anomalies of the LRV are more complex than those of the RRV. The renal vein
      anatomy can be well depicted by MDCT angiography. Our new classification of the
      renal vein variations will improve the recognition of the renal vein morphology
      preoperatively.

PMID- 25567099
TI  - A toolkit enabling efficient, scalable and reproducible gene tagging in
      trypanosomatids.
AB  - One of the first steps in understanding a protein's function is to determine its
      localization; however, the methods for localizing proteins in some systems have
      not kept pace with the developments in other fields, creating a bottleneck in the
      analysis of the large datasets that are generated in the post-genomic era. To
      address this, we developed tools for tagging proteins in trypanosomatids. We made
      a plasmid that, when coupled with long primer PCR, can be used to produce
      transgenes at their endogenous loci encoding proteins tagged at either terminus
      or within the protein coding sequence. This system can also be used to generate
      deletion mutants to investigate the function of different protein domains. We
      show that the length of homology required for successful integration precluded
      long primer PCR tagging in Leishmania mexicana. Hence, we developed plasmids and
      a fusion PCR approach to create gene tagging amplicons with sufficiently long
      homologous regions for targeted integration, suitable for use in trypanosomatids
      with less efficient homologous recombination than Trypanosoma brucei.
      Importantly, we have automated the primer design, developed universal PCR
      conditions and optimized the workflow to make this system reliable, efficient and
      scalable such that whole genome tagging is now an achievable goal. 

PMID- 25567098
TI  - A new look at sodium channel beta subunits.
AB  - Voltage-gated sodium (Nav) channels are intrinsic plasma membrane proteins that
      initiate the action potential in electrically excitable cells. They are a major
      focus of research in neurobiology, structural biology, membrane biology and
      pharmacology. Mutations in Nav channels are implicated in a wide variety of
      inherited pathologies, including cardiac conduction diseases, myotonic
      conditions, epilepsy and chronic pain syndromes. Drugs active against Nav
      channels are used as local anaesthetics, anti-arrhythmics, analgesics and anti
      convulsants. The Nav channels are composed of a pore-forming alpha subunit and
      associated beta subunits. The beta subunits are members of the immunoglobulin
      (Ig) domain family of cell-adhesion molecules. They modulate multiple aspects of
      Nav channel behaviour and play critical roles in controlling neuronal
      excitability. The recently published atomic resolution structures of the human
      beta3 and beta4 subunit Ig domains open a new chapter in the study of these
      molecules. In particular, the discovery that beta3 subunits form trimers suggests
      that Nav channel oligomerization may contribute to the functional properties of
      some beta subunits. 

PMID- 25567103
TI  - Fetal growth and the ethnic origins of type 2 diabetes.
AB  - Birthweight is known to differ by ethnicity, with South Asian, black African and
      Caribbean, and Hispanic ethnic groups having lower birthweight on average, when
      compared with people of white European ethnicity. Birthweight is the most
      frequently used proxy of fetal growth, and represents the net effect of a host of
      genetic, physiological and pathophysiological factors. These same ethnic groups
      that have lower average birthweight also tend to have a higher prevalence of type
      2 diabetes in adulthood. It is not unreasonable to propose that the well
      established inverse association between birthweight and risk of type 2 diabetes
      may at least partially contribute to these differences in prevalence of type 2
      diabetes between ethnic groups. This hypothesis would rely on the mechanisms that
      drive the ethnic differences in birthweight aligning with those that modify the
      risk of type 2 diabetes. In this issue of Diabetologia (DOI: 10.1007/s00125-014
      3474-7), Nightingale et al have furthered this field by determining whether
      ethnic differences in markers of cardio-metabolic risk are consistent with the
      differences in birthweight in an ethnically diverse cohort of children. The
      likely contribution of fetal growth to ethnic differences in risk of type 2
      diabetes and cardiovascular disease is discussed, particularly in light of the
      magnitude of the birthweight differences, as are implications for the prevention
      of type 2 diabetes.

PMID- 25567104
TI  - Highly efficient synthesis of novel methyl 13(2)-methylene mesopyropheophorbide a
      and its stereoselective Michael addition reaction.
AB  - Treatment of methyl mesopyropheophorbide a with formaldehyde under basic
      conditions gave a novel 13(2)-methylene derivative in 85% yield; under acidic
      conditions, the corresponding 20-hydroxymethyl derivative was obtained in 65%
      yield. The high reactivity of the enone structural motif existed in the former
      product provides a unique way to construct some novel chlorophyll a derivatives
      for various applications. Stereoselective Michael reaction of this compound is
      studied and discussed. 

PMID- 25567102
TI  - Birthweight, mediating biomarkers and the development of type 2 diabetes later in
      life: a prospective study of multi-ethnic women.
AB  - AIMS/HYPOTHESIS: The aim of this work was to investigate the prospective
      relationship between low birthweight (LBW) and type 2 diabetes risk later in life
      and the mediation effects of type 2 diabetes biomarkers linking LBW to type 2
      diabetes risk. METHODS: We measured baseline plasma concentrations of various
      type 2 diabetes biomarkers in 1,259 incident type 2 diabetes cases and 1,790
      controls in the Women's Health Initiative-Observational Study. Self-report
      birthweights of the participants were recorded. The total effect of LBW on type 2
      diabetes risk was partitioned into effects that were mediated by a specific
      biomarker and effects that were not mediated by this biomarker, using
      counterfactual model-based mediation analysis. RESULTS: LBW was significantly
      associated with increased risk of type 2 diabetes. Compared with women with
      birthweight 3.63-4.54 kg, women with LBW (<2.72 kg) had a multivariable-adjusted
      OR of 2.15 (95% CI, 1.54, 3.00). Insulin resistance (indicated by HOMA-IR)
      mediated 47% of the total effect. Decreased sex hormone-binding globulin (SHBG)
      concentration accounted for 24%, elevated E-selectin concentration accounted for
      25% and increased systolic blood pressure accounted for 8% of the total effect of
      LBW on type 2 diabetes risk. (Due to interactions among different mediators, the
      sum of each individual mediator's contribution could exceed 100%, without an
      upper limit.) CONCLUSIONS/INTERPRETATION: LBW is directly predictive of higher
      risk of type 2 diabetes later in life. The effect of LBW on type 2 diabetes risk
      seems mainly mediated by insulin resistance, which is further explained by
      circulating levels of SHBG and E-selectin and systolic blood pressure. The study
      provides potential risk stratification in a population at greater risk of
      developing type 2 diabetes.

PMID- 25567105
TI  - Clostridium difficile infection: risk factors, diagnosis and management.
AB  - OPINION STATEMENT: Clostridium difficile infection (CDI) is the leading cause of
      death due to gastrointestinal infections in the US and is the most common cause
      of nosocomial diarrhea. The emergence of a hypervirulent strain in the early
      2000s has been associated with a dramatic increase in the number and severity of
      cases in the US, Canada, and several other countries. Most cases are related to
      antibiotic use, but sporadic cases occur in otherwise healthy individuals with no
      risk factors. Morbidity and mortality are highest in the elderly. Diagnosis is
      confirmed by detection of C. difficile toxin in the stools. Treatment should be
      stratified by severity of disease, with metronidazole use for mild disease cases
      and vancomycin for severe disease. Recurrent CDI occurs in 10-20 % of cases. A
      first recurrence can be treated with a ten-day regimen of metronidazole or
      vancomycin; a second recurrence is best treated by a pulsed regimen of
      vancomycin. In patients with multiple (three or more) recurrences, fecal
      microbiota transplant has a high rate of success. The most important methods of
      prevention are wise antibiotic policies, hand hygiene, isolation, and barrier
      methods in hospital and long-term care facilities (LCTF) settings.

PMID- 25567107
TI  - Spectroscopic study of ionic liquid adsorption from solution onto gold.
AB  - Gold was exposed to ethanol solutions containing 0.1 wt% 1-hexyl-3-methyl
      imidazolium bis(trifluoromethanesulfonyl)imide (HMIM NTf2), an ionic liquid (IL).
      The resulting adsorbed layers were interrogated using X-ray photoelectron
      spectroscopy (XPS - both conventional and synchrotron-based) and spectroscopic
      ellipsometry. Ellipsometry indicated that the adsorbed layer thickness was
      smaller than the size of an IL ion pair, with an average determined layer
      thickness of 0.15 nm. This value indicates that the adsorbed layer on gold is
      most likely patchy. Conventional XPS revealed that the IL adsorbs irreversibly to
      gold, with equal amounts of anion and cation in the adsorbed layer. High signal
      to-noise synchrotron XPS spectra permitted detailed deconvolution of the S 2p and
      N 1s peaks for the IL-treated gold, providing more information on adsorbed layer
      composition and structure. Spectra acquired as a function of X-ray exposure time
      indicate that non-interacting physisorbed IL components are preferentially
      removed at the expense of surface bound components, and that anion and cation are
      both present in the surface bound layer, and also in the layer above. A model
      structure for the IL adsorbed on gold is proposed. 

PMID- 25567106
TI  - Diagnostic and Management Implications of Basic Science Advances in Barrett's
      Esophagus.
AB  - OPINION STATEMENT: Barrett's esophagus (BE) is a well-established premalignant
      condition for esophageal adenocarcinoma (EAC), a cancer that has increased in the
      Western world by nearly sixfold over the past three decades and is associated
      with a dismal 5-year survival rate (<20 %) especially when detected at a
      symptomatic state. Given the dramatic rise in EAC incidence and poor outcomes,
      much attention has focused on screening and surveillance in BE with a goal of
      identifying curable lesions and improving outcomes in patients with EAC. The
      limitations of current screening and surveillance strategies provide the
      necessary impetus to improve diagnostic accuracy and risk stratification of
      patients with BE. Biomarkers have the potential to predict risk of progression to
      cancer, identify patients most likely to respond to endoscopic eradication
      therapies, and ultimately influence patient management and outcomes. The goal of
      identifying such a biomarker or panel of biomarkers ready for clinical
      application remains elusive. This review highlights the recent advances in the
      field of biomarkers. It is increasingly being recognized that a single biomarker
      is suboptimal in accurate clinical risk stratification of individuals at highest
      risk for progression to cancer and an ideal risk stratification tool should
      include a panel of biomarkers in conjunction with clinical and endoscopic
      factors. Finally, we review advances in our screening strategies with use of
      Cytosponge, transnasal endoscopy, and tethered capsule endomicroscopy and
      surveillance strategies with use of advanced imaging techniques. Feasibility of
      these novel technologies for large population screening and surveillance needs to
      be assessed in future trials.

PMID- 25567108
TI  - Assembly of tetrameric dimethyltin-functionalized selenotungstates: from
      nanoclusters to one-dimensional chains.
AB  - Two unprecedented tetrameric selenotungstates based on different Wells-Dawson
      type fragments have been obtained: the {Sn7Se8W54} nanocluster exhibiting
      photocatalytic H2 evolution activity and the {Sn16Se11W56} chain, which are the
      first dimethyltin-functionalized selenotungstates reported and contain the unique
      {beta-Se2W15} and {gamma-Se2W14} building blocks, respectively. 

PMID- 25567109
TI  - Dynamic firing properties of type I spiral ganglion neurons.
AB  - Spiral ganglion neurons, the first neural element in the auditory system, possess
      complex intrinsic properties, possibly required to process frequency-specific
      sensory input that is integrated with extensive efferent regulation. Together
      with their tonotopically-graded sizes, the somata of these neurons reveal a
      sophisticated electrophysiological profile. Type I neurons, which make up ~95 %
      of the ganglion, have myriad voltage-gated ion channels that not only vary along
      the frequency contour of the cochlea, but also can be modulated by regulators
      such as voltage, calcium, and second messengers. The resultant developmentally-
      and tonotopically-regulated neuronal firing patterns conform to three distinct
      response modes (unitary, rapid, and slow) based on threshold and accommodation.
      This phenotype, however, is not static for any individual type I neuron. Recent
      observations have shown that, as neurons become less excitable with age, they
      demonstrate enhanced plasticity enabling them to change from one response mode to
      another depending upon resting membrane potential and the presence of
      neurotrophin-3. Thus, the primary auditory afferents utilized to encode dynamic
      acoustic stimuli possess the intrinsic specializations that allow them
      dynamically to alter their firing pattern. 

PMID- 25567110
TI  - Neurofilament dynamics and involvement in neurological disorders.
AB  - Neurons are extremely polarised cells in which the cytoskeleton, composed of
      microtubules, microfilaments and neurofilaments, plays a crucial role in
      maintaining structure and function. Neurofilaments, the 10-nm intermediate
      filaments of neurons, provide structure and mechanoresistance but also provide a
      scaffolding for the organization of the nucleus and organelles such as
      mitochondria and ER. Disruption of neurofilament organization and expression or
      metabolism of neurofilament proteins is characteristic of certain neurological
      syndromes including Amyotrophic Lateral Sclerosis, Charcot-Marie-Tooth
      sensorimotor neuropathies and Giant Axonal Neuropathy. Microfluorometric live
      imaging techniques have been instrumental in revealing the dynamics of
      neurofilament assembly and transport and their functions in organizing
      intracellular organelle networks. The insolubility of neurofilament proteins has
      limited identifying interactors by conventional biochemical techniques but yeast
      two-hybrid experiments have revealed new roles for oligomeric, nonfilamentous
      structures including vesicular trafficking. Although having long half-lives, new
      evidence points to degradation of subunits by the ubiquitin-proteasome system as
      a mechanism of normal turnover. Although certain E3-ligases ubiquitinating
      neurofilament proteins have been identified, the overall process of neurofilament
      degradation is not well understood. We review these mechanisms of neurofilament
      homeostasis and abnormalities in motor neuron and peripheral nerve disorders.
      Much remains to discover about the disruption of processes that leads to their
      pathological aggregation and accumulation and the relevance to pathogenesis.
      Understanding these mechanisms is crucial for identifying novel therapeutic
      strategies. 

PMID- 25567112
TI  - Non-volatile organic transistor memory devices using the poly(4-vinylpyridine)
      based supramolecular electrets.
AB  - Supramolecular electrets consisting of poly(4-vinylpyridine) (P4VP) and
      conjugated molecules of phenol, 2-naphthol and 2-hydroxyanthracene were
      investigated for non-volatile transistor memory applications. The memory windows
      of these supramolecular electret devices were significantly enhanced upon
      increasing the pi-conjugation size of the molecule. A high ON/OFF current ratio
      of more than 10(7) over 10(4) s was achieved on the supramolecule based memory
      devices. 

PMID- 25567111
TI  - Factors affecting delay in seeking treatment among malaria patients along
      Thailand-Myanmar border in Tak Province, Thailand.
AB  - BACKGROUND: Malaria is a major health problem in Thailand, especially in areas
      adjacent to the borders of Myanmar. Delay in seeking treatment is an important
      factor in the development of severe complications, death and the transmission of
      the disease. This study aimed to investigate factors affecting delays in seeking
      treatment of malaria patients. METHODS: A cross-sectional analytic study was
      conducted in 456 malaria patients along the Thailand-Myanmar border. Patients
      were selected by stratified sampling from 11 malaria clinics and five public
      hospitals in Tak Province, Thailand. Data were collected by the use of a
      structured interview questionnaire and from patient's medical records. RESULTS:
      The majority of patients were categorized with an ethnicity of 'hill tribe'
      (65.8%), followed by Thai (34.2%). Seventy-nine per cent of patients delayed
      seeking treatment. A simple logistic regression identified significant factors
      affecting delays in seeking treatment: people of "hill tribe" ethnicity;
      plasmodium species; self-treatment; visiting sub-district health promotion
      hospital/malaria post before visiting a malaria clinic or public hospital; and
      low to medium social support. After being subjected to multivariate analysis,
      factors significantly associated with the delay were "hill tribe" ethnicity
      (ORadj = 2.32, 95% CI: 1.34-4.04); infection with P.vivax (ORadj=2.02, 95% CI:
      1.19-3.41; self-treatment (ORadj = 1.73, 95% CI: 1.04-2.85); and receiving a low
      degree of social support (ORadj = 2.58, 95% CI: 1.24-5.35). CONCLUSIONS: Emphasis
      should be placed on need for early diagnosis and treatment in malaria patients as
      well as on ensuring the first facility for detection and treatment of malaria is
      a malaria clinic or public hospital, and the promotion of social support. These
      are especially important issues for the health of hill tribe people.

PMID- 25567113
TI  - Torsional behaviors of polymer-infiltrated carbon nanotube yarn muscles studied
      with atomic force microscopy.
AB  - Torsional behaviors of polymer-infiltrated carbon nanotube (CNT) yarn muscles
      have been investigated in relation to molecular architecture by using atomic
      force microscopy (AFM). Two polymers with different stiffnesses, polystyrene (PS)
      and poly(styrene-b-isoprene-b-styrene) (SIS), were uniformly infiltrated into CNT
      yarns for electrothermal torsional actuation. The torsional behaviors of hybrid
      yarn muscles are completely explained by the volume change of each polymer, based
      on the height and full width at half maximum profiles from the AFM morphological
      images. The volume expansion of the PS yarn muscle (1.7 nm of vertical change and
      22 nm of horizontal change) is much larger than that of the SIS yarn muscle (0.3
      nm and 11 nm change in vertical and horizontal directions) at 80  degrees C,
      normalized by their values at 25  degrees C. We demonstrate that their maximum
      rotations are consequently 29.7 deg mm(-1) for the PS-infiltrated CNT yarn muscle
      (relatively larger rotation) and 14.4 deg mm(-1) for the SIS-infiltrated CNT yarn
      muscle (smaller rotation) at 0.75 V m(-1). These hybrid yarn muscles could be
      applied in resonant controllers or damping magnetoelectric sensors. 

PMID- 25567114
TI  - Response to "The International Monetary Fund and the Ebola outbreak".

PMID- 25567115
TI  - Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy
      and safety from a phase IIa randomised multicentre study.
AB  - OBJECTIVE: Interleukin 13 (IL-13) is thought to play a key role as an effector
      cytokine in UC. Anrukinzumab, a humanised antibody that inhibits human IL-13, was
      evaluated for the treatment of UC. DESIGN: In a multicentre, randomised, double
      blind, placebo-controlled study, patients with active UC (Mayo score >=4 and <10)
      were randomised to anrukinzumab 200, 400 or 600 mg or placebo. Patients received
      five intravenous administrations over 14 weeks. The primary endpoint was fold
      change from baseline in faecal calprotectin (FC) at Week 14. Secondary endpoints
      included safety, pharmacokinetics and IL-13 levels. RESULTS: The modified
      intention-to-treat population included 84 patients (21 patients/arm). Fold change
      of FC from baseline at Week 14 was not significantly different for any treatment
      groups compared with the placebo. The study had a high dropout rate, in part,
      related to lack of efficacy. The exploratory comparisons of each dose were not
      significantly different from placebo in terms of change from baseline in total
      Mayo score, clinical response, clinical remission and proportion of subjects with
      mucosal healing. An increase in serum total IL-13 (free and bound to
      anrukinzumab) was observed for all anrukinzumab groups but not with placebo. This
      suggests significant binding of anrukinzumab to IL-13. The safety profile was not
      different between the anrukinzumab and placebo groups. CONCLUSIONS: A
      statistically significant therapeutic effect of anrukinzumab could not be
      demonstrated in patients with active UC in spite of binding of anrukinzumab to IL
      13. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number NCT01284062.

PMID- 25567116
TI  - Fair prices for new direct-acting antiviral agents (DAAs) to make treatment for
      all affordable.

PMID- 25567117
TI  - Stratification of hepatocellular carcinoma risk in primary biliary cirrhosis: a
      multicentre international study.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC) is an infrequent yet critical event in
      primary biliary cirrhosis (PBC); however, predictive tools remain ill-defined.
      Our objective was to identify candidate risk factors for HCC development in
      patients with PBC. DESIGN: Risk factor analysis was performed in over 15 centres
      from North America and Europe spanning >40 years observation period using Cox
      proportional hazards assumptions, logistic regression, and Kaplan-Meier
      estimates. RESULTS: Of 4565 patients with PBC 123 developed HCC, yielding an
      incidence rate (IR) of 3.4 cases/1000 patient-years. HCC was significantly more
      common in men (p<0.0001), and on univariate analysis factors at PBC diagnosis
      associated with future HCC development were male sex (unadjusted HR 2.91,
      p<0.0001), elevated serum aspartate transaminase (HR 1.24, p<0.0001), advanced
      disease (HR 2.72, p=0.022), thrombocytopenia (HR 1.65, p<0.0001), and hepatic
      decompensation (HR 9.89, p<0.0001). As such, non-treatment with ursodeoxycholic
      acid itself was not associated with cancer development; however, 12-month
      stratification by biochemical non-response (Paris-I criteria) associated
      significantly with future risk of HCC (HR 4.52, p<0.0001; IR 6.6 vs 1.4,
      p<0.0001). Non-response predicted future risk in patients with early stage
      disease (IR 4.7 vs 1.2, p=0.005), advanced disease (HR 2.79, p=0.02; IR 11.2 vs
      4.4, p=0.033), and when restricting the analysis to only male patients (HR 4.44,
      p<0.001; IR 18.2 vs 5.4, p<0.001). On multivariable analysis biochemical non
      response remained the most significant factor predictive of future HCC risk
      (adjusted HR 3.44, p<0.0001). CONCLUSIONS: This uniquely powered, internationally
      representative cohort robustly demonstrates that 12-month biochemical non
      response is associated with increased future risk of developing HCC in PBC. Such
      risk stratification is relevant to patient care and development of new therapies.

PMID- 25567118
TI  - Geographical patterns of the standing and active human gut microbiome in health
      and IBD.
AB  - OBJECTIVE: A global increase of IBD has been reported, especially in countries
      that previously had low incidence rates. Also, the knowledge of the human gut
      microbiome is steadily increasing, however, limited information regarding its
      variation on a global scale is available. In the light of the microbial
      involvement in IBDs, we aimed to (1) identify shared and distinct IBD-associated
      mucosal microbiota patterns from different geographical regions including Europe
      (Germany, Lithuania) and South Asia (India) and (2) determine whether profiling
      based on 16S rRNA transcripts provides additional resolution, both of which may
      hold important clinical relevance. DESIGN: In this study, we analyse a set of 89
      mucosal biopsies sampled from individuals of German, Lithuanian and Indian
      origins, using bacterial community profiling of a roughly equal number of healthy
      controls, patients with Crohn's disease and UC from each location, and analyse
      16S rDNA and rRNA as proxies for standing and active microbial community
      structure, respectively. RESULTS: We find pronounced population-specific as well
      as general disease patterns in the major phyla and patterns of diversity, which
      differ between the standing and active communities. The geographical origin of
      samples dominates the patterns of beta diversity with locally restricted disease
      clusters and more pronounced effects in the active microbial communities.
      However, two genera belonging to the Clostridium leptum subgroup, Faecalibacteria
      and Papillibacter, display consistent patterns with respect to disease status and
      may thus serve as reliable 'microbiomarkers'. CONCLUSIONS: These analyses reveal
      important interactions of patients' geographical origin and disease in the
      interpretation of disease-associated changes in microbial communities and
      highlight the added value of analysing communities on both the 16S rRNA gene
      (DNA) and transcript (RNA) level.

PMID- 25567119
TI  - Safety and immunogenicity of a freeze-dried, Vero cell culture-derived,
      inactivated Japanese encephalitis vaccine (KD-287, ENCEVAC(r)) versus a mouse
      brain-derived inactivated Japanese encephalitis vaccine in children: a phase III,
      multicenter, double-blinded, randomized trial.
AB  - BACKGROUND: Although mouse brain-derived, inactivated Japanese encephalitis
      vaccines (JE-MBs) have been successfully used for a long time, potential rare
      neurological complications have prompted the development of a Vero cell culture
      derived inactivated vaccine (JE-VC). In a phase III clinical study, we aimed to
      compare the safety and immunogenicity of a JE-VC, KD-287 with a JE-MB, JEV-GCC,
      in children. METHODS: In this multicenter, double-blinded, randomized controlled
      trial, the study population consisted of 205 healthy Korean children aged 12-23
      months. Each subject was subcutaneously vaccinated with either KD-287 or JEV-GCC
      twice at an interval of 2 weeks and then vaccinated once 12 months after the
      second vaccination. Neutralizing antibodies were measured by the plaque reduction
      neutralization test using the homologous and heterologous, as a post hoc
      analysis, challenge virus strains. RESULTS: The three-dose regimen of KD-287
      showed a comparable safety profile with JEV-GCC except higher incidence of fever
      after the first dose (30.4% and 14.7%, respectively). Most of the fever was mild
      degree (61.3% and 66.7%, respectively). KD-287 fulfilled the non-inferiority
      criteria for seroconversion rate (SCR) and geometric mean titer (GMT) of the
      neutralizing antibody, which were the primary endpoints, at 4 weeks after the
      third vaccination (95% CI: -1.00, 3.10 for the SCR difference and 10.8, 17.6 for
      the GMT ratio). The SCRs of KD-287 were all 100% and the GMTs were higher in the
      KD-287 group than in the JEV-GCC group after the second vaccination and before
      and after the third vaccination (GMT ratio: 5.59, 20.13, and 13.79, respectively,
      p < 0.001 in all). GMTs were higher in the KD-287 group in the heterologous
      analysis also (GMT ratio: 4.05, 5.15, and 4.19, respectively, p < 0.001 in all).
      CONCLUSIONS: This study suggests that the KD-287, a JE-VC is as safe as and may
      be more effective than the licensed MB-derived vaccine. KD-287 could thus be
      useful as a second-generation vaccine and substitute for the current JE-MB
      vaccine in Korean children. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01150942.

PMID- 25567120
TI  - Anodal tDCS Combined With Radial Nerve Stimulation Promotes Hand Motor Recovery
      in the Acute Phase After Ischemic Stroke.
AB  - BACKGROUND AND OBJECTIVE: The question of the best therapeutic window in which
      noninvasive brain stimulation (NIBS) could potentiate the plastic changes for
      motor recovery after a stroke is still unresolved. Most of the previous NIBS
      studies included patients in the chronic phase of recovery and very few in the
      subacute or acute phase. We investigated the effect of transcranial direct
      current stimulation (tDCS) combined with repetitive peripheral nerve stimulation
      (rPNS) on the time course of motor recovery in the acute phase after a stroke.
      METHODS: Twenty patients enrolled within the first few days after a stroke were
      randomized in 2 parallel groups: one receiving 5 consecutive daily sessions of
      anodal tDCS over the ipsilesional motor cortex in association with rPNS and the
      other receiving the same rPNS combined with sham tDCS. Motor performance (primary
      endpoint: Jebsen and Taylor Hand Function Test [JHFT]) and transcranial magnetic
      stimulation cortical excitability measures were obtained at baseline (D1), at the
      end of the treatment (D5), and at 2 and 4 weeks' follow-up (D15 and D30).
      RESULTS: The time course of motor recovery of the 2 groups of patients was
      different and positively influenced by the intervention (Group * Time interaction
      P = .01). The amount of improvement on the JHFT was greater at D15 and D30 in the
      anodal tDCS group than in the sham group. CONCLUSION: These results show that
      early cortical neuromodulation with anodal tDCS combined with rPNS can promote
      motor hand recovery and that the benefit is still present 1 month after the
      stroke.

PMID- 25567121
TI  - A Randomized Controlled Trial to Reduce Falls in People With Parkinson's Disease.
AB  - BACKGROUND: Falls are common and disabling in people with Parkinson's disease
      (PD). There is a need to quantify the effects of movement rehabilitation on falls
      in PD. OBJECTIVE: To evaluate 2 physical therapy interventions in reducing falls
      in PD. METHODS: We randomized 210 people with PD to 3 groups: progressive
      resistance strength training coupled with falls prevention education, movement
      strategy training combined with falls prevention education, and life-skills
      information (control). All received 8 weeks of out-patient therapy once per week
      and a structured home program. The primary end point was the falls rate, recorded
      prospectively over a 12 month period, starting from the completion of the
      intervention. Secondary outcomes were walking speed, disability, and quality of
      life. RESULTS: A total of 1547 falls were reported for the trial. The falls rate
      was higher in the control group compared with the groups that received strength
      training or strategy training. There were 193 falls for the progressive
      resistance strength training group, 441 for the movement strategy group and 913
      for the control group. The strength training group had 84.9% fewer falls than
      controls (incidence rate ratio [IRR] = 0.151, 95% CI 0.071-0.322, P < .001). The
      movement strategy training group had 61.5% fewer falls than controls (IRR =
      0.385, 95% CI 0.184-0.808, P = .012). Disability scores improved in the
      intervention groups following therapy while deteriorating in the control group.
      CONCLUSIONS: Rehabilitation combining falls prevention education with strength
      training or movement strategy training reduces the rate of falls in people with
      mild to moderately severe PD and is feasible.

PMID- 25567122
TI  - Changes in Strength, Sensation, and Prehension in Acute Cervical Spinal Cord
      Injury: European Multicenter Responsiveness Study of the GRASSP.
AB  - OBJECTIVE: To investigate the internal and external responsiveness and recovery
      profiles of the Graded Redefined Assessment of Strength, Sensibility, and
      Prehension (GRASSP) instrument in revealing changes in upper limb function within
      the first year following cervical spinal cord injury (SCI). METHOD: A European
      prospective, longitudinal, multicenter study assessing the GRASSP at 1, 3, 6, and
      12 months after cervical SCI. Subtests of GRASSP were compared to the upper
      extremity motor (UEMS) and light touch scores (LT) according to the International
      Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI), the
      Spinal Cord Independence Measure self-care subscore (SCIM-SS), as well as a
      clinician-rated outcome measure (CROM) of clinical relevance. Data were analyzed
      for GRASSP responsiveness and recovery rate over time. RESULTS: Seventy-four
      participants entered the study. GRASSP subtests proved responsive (standardized
      response mean [SRM] ranged from 0.79 to 1.48 for strength, 0.50 to 1.03 for
      prehension, and 0.14 to 0.64 for sensation) between all examination time points.
      In comparison, UEMS and LT showed lower responsiveness (SRM UEMS ranged from 0.69
      to 1.29 and SRM LT ranged from 0.30 to -0.13). All GRASSP subtests revealed
      significant, moderate-to-excellent correlations with UEMS, LT, and SCIM-SS at
      each time point, and changes in GRASSP subtests were in accordance with the CROM.
      GRASSP prehension and motor recovery was largest between 1 and 3 months.
      CONCLUSION: The GRASSP showed excellent responsiveness, detecting distinct
      changes in strength and prehension relating to the severity of cervical SCI. It
      detected clinically significant changes complimentary to the ISNCSCI and SCIM-SS
      assessments.

PMID- 25567123
TI  - The Problematic Support Scale: A validation among patients with systemic lupus
      erythematosus.
AB  - The aim of the study was to develop and to assess the psychometric properties of
      the Problematic Support Scale, among patients with systemic lupus erythematosus.
      An online questionnaire was filled in by 344 systemic lupus erythematosus
      patients with a mean age of 39.66 years. Explorative factor analysis, later
      validated by confirmative factor analysis, showed the emergence of a two-factor
      structure in types of support provided: denying/uninformed support and oppressive
      support. Denying/uninformed support includes offers of support that neglect the
      disease manifestations and consequences. Oppressive support describes social
      support offers which are perceived as excessive and oppressive. Results confirm
      previous qualitative evidence and demonstrate good reliability and concurrent
      validity of the Problematic Support Scale. Theoretical and methodological
      implications for the study of social support are discussed.

PMID- 25567126
TI  - The Society for Implementation Research Collaboration Instrument Review Project:
      a methodology to promote rigorous evaluation.
AB  - BACKGROUND: Identification of psychometrically strong instruments for the field
      of implementation science is a high priority underscored in a recent National
      Institutes of Health working meeting (October 2013). Existing instrument reviews
      are limited in scope, methods, and findings. The Society for Implementation
      Research Collaboration Instrument Review Project's objectives address these
      limitations by identifying and applying a unique methodology to conduct a
      systematic and comprehensive review of quantitative instruments assessing
      constructs delineated in two of the field's most widely used frameworks, adopt a
      systematic search process (using standard search strings), and engage an
      international team of experts to assess the full range of psychometric criteria
      (reliability, construct and criterion validity). Although this work focuses on
      implementation of psychosocial interventions in mental health and health-care
      settings, the methodology and results will likely be useful across a broad
      spectrum of settings. This effort has culminated in a centralized online open
      access repository of instruments depicting graphical head-to-head comparisons of
      their psychometric properties. This article describes the methodology and
      preliminary outcomes. METHODS: The seven stages of the review, synthesis, and
      evaluation methodology include (1) setting the scope for the review, (2)
      identifying frameworks to organize and complete the review, (3) generating a
      search protocol for the literature review of constructs, (4) literature review of
      specific instruments, (5) development of an evidence-based assessment rating
      criteria, (6) data extraction and rating instrument quality by a task force of
      implementation experts to inform knowledge synthesis, and (7) the creation of a
      website repository. RESULTS: To date, this multi-faceted and collaborative search
      and synthesis methodology has identified over 420 instruments related to 34
      constructs (total 48 including subconstructs) that are relevant to implementation
      science. Despite numerous constructs having greater than 20 available
      instruments, which implies saturation, preliminary results suggest that few
      instruments stem from gold standard development procedures. We anticipate
      identifying few high-quality, psychometrically sound instruments once our
      evidence-based assessment rating criteria have been applied. CONCLUSIONS: The
      results of this methodology may enhance the rigor of implementation science
      evaluations by systematically facilitating access to psychometrically validated
      instruments and identifying where further instrument development is needed.

PMID- 25567128
TI  - Assisted reproductive technology has low complication risk, US data show.

PMID- 25567127
TI  - Consumption of Bt rice pollen containing Cry1C or Cry2A does not pose a risk to
      Propylea japonica (Thunberg) (Coleoptera: Coccinellidae).
AB  - As a pollen feeder, Propylea japonica would be directly exposed to Cry proteins
      in Bacillus thuringiensis (Bt)-transgenic rice fields. The effect of Cry1C- or
      Cry2A-containing transgenic rice pollen on the fitness of P. japonica was
      assessed using two dietary-exposure experiments in the laboratory. In the first
      experiment, larval developmental time of P. japonica was significantly longer
      when fed pollen from Bt rice lines rather than control pollen but other life
      table parameters were not significantly affected. In the second experiment, P.
      japonica was not affected when fed a rapeseed pollen-based diet containing
      purified Cry1C or Cry2A at concentrations that were >10-times higher than in
      pollen, but P. japonica was affected when the diet contained E-64 as a positive
      control. In both experiments, the stability and bioactivity of the Cry proteins
      in the food sources and the uptake of the proteins by P. japonica were confirmed.
      The results show that P. japonica is not sensitive to Cry1C or Cry2A proteins;
      the effect observed in the first experiment was likely attributable to unknown
      differences in the nutritional composition of Bt rice pollen. Overall, the data
      indicate that the growing of Cry1C- or Cry2A-transgenic rice should pose a
      negligible risk to P. japonica. 

PMID- 25567129
TI  - The tyrosine kinase Itk suppresses CD8+ memory T cell development in response to
      bacterial infection.
AB  - Vaccine efficacy depends on strong long-term development of immune memory and the
      formation of memory CD8(+) T cells is critical for recall responses to infection.
      Upon antigen recognition by naive T cells, the strength of the TcR signal
      influences the subsequent effector and memory cells differentiation. Here, we
      have examined the role of Itk, a tyrosine kinase critical for TcR signaling, in
      CD8(+) effector and memory T cell differentiation during Listeria monocytogenes
      infection. We found that the reduced TcR signal strength in Itk deficient naive
      CD8(+) T cells enhances the generation of memory T cells during infection. This
      is accompanied by increased early Eomesodermin, IL-7Ralpha expression and memory
      precursor effector cells. Furthermore, Itk is required for optimal cytokine
      production in responding primary effector cells, but not secondary memory
      responses. Our data suggests that Itk-mediated signals control the expression of
      Eomesodermin and IL-7Ralpha, thus regulating the development of memory CD8(+) T
      cells, but not subsequent response of memory cells. 

PMID- 25567130
TI  - The MDM2 Inhibitor AMG 232 Demonstrates Robust Antitumor Efficacy and Potentiates
      the Activity of p53-Inducing Cytotoxic Agents.
AB  - p53 is a critical tumor suppressor and is the most frequently inactivated gene in
      human cancer. Inhibition of the interaction of p53 with its negative regulator
      MDM2 represents a promising clinical strategy to treat p53 wild-type tumors. AMG
      232 is a potential best-in-class inhibitor of the MDM2-p53 interaction and is
      currently in clinical trials. We characterized the activity of AMG 232 and its
      effect on p53 signaling in several preclinical tumor models. AMG 232 binds the
      MDM2 protein with picomolar affinity and robustly induces p53 activity, leading
      to cell-cycle arrest and inhibition of tumor cell proliferation. AMG 232
      treatment inhibited the in vivo growth of several tumor xenografts and led to
      complete and durable regression of MDM2-amplified SJSA-1 tumors via growth arrest
      and induction of apoptosis. Therapeutic combination studies of AMG 232 with
      chemotherapies that induce DNA damage and p53 activity resulted in significantly
      superior antitumor efficacy and regression, and markedly increased activation of
      p53 signaling in tumors. These preclinical data support the further evaluation of
      AMG 232 in clinical trials as both a monotherapy and in combination with standard
      of-care cytotoxics.

PMID- 25567131
TI  - A pilot randomized controlled trial comparing CABG surgery performed with total
      arterial grafts or without.
AB  - OBJECTIVE: To date only a few randomized controlled studies have compared
      grafting strategies in patients with multi-vessel coronary disease. This study
      represents a pilot RCT designed to test the feasibility of a trial comparing
      conventional CABG performed with a LIMA-LAD plus saphenous vein grafts (LIMA+SVG)
      and CABG performed with total arterial grafting (TAG). METHODS: Consenting
      patients undergoing non-redo isolated CABG surgery at a single institution were
      randomized to TAG or LIMA+SVG groups. Exclusion criteria included prior CABG,
      emergent procedure, concomitant procedure, varicose veins and renal dysfunction.
      The primary endpoints were: enrolment >20% and completion of CT coronary
      angiography at 6 months >80%. Statistical investigation was performed on an
      intention to treat analysis. RESULTS: Of 421 eligible patients, 60 were enrolled
      and 2 withdrew (n = 30 in TAG, n = 28 LIMA+SVG) for 14% enrolment rate. Patient
      characteristics were similar in each group. No patients died in hospital and
      adverse events such as MI, stroke and deep sternal wound infection were not
      significantly different between groups. Clinical follow-up was complete in 100%
      of patients, with 44/58 (76%) undergoing CT coronary angio at 6 months. Graft
      occlusion occurred in 2 patients in each group for patency rates of 89% (TAG) and
      91% (LIMA+SVG). CONCLUSIONS: We provide evidence that an RCT comparing grafting
      strategy is possible but also show that achieving recruitment or follow-up CT may
      be difficult. Given the excellent patency results and little difference between
      groups, our findings suggest that the sample size required may make it infeasible
      to compare graft patency at 6 months as a study end-point. TRIAL REGISTRATION:
      Randomized Controlled Trial number: ISRCTN80270323 . Few RCT's exist comparing
      conventional CABG performed with a LIMA-LAD plus saphenous vein grafts (LIMA+SVG)
      compared to CABG performed with total arterial grafting (TAG). This study is a
      pilot RCT designed to test the feasibility of such a trial and identify pitfalls.

PMID- 25567132
TI  - High expression of EVI1 and MEL1 is a compelling poor prognostic marker of
      pediatric AML.
AB  - EVI1 and MEL1 are homolog genes whose transcriptional activations by chromosomal
      translocations are known in small subsets of leukemia. From gene expression
      profiling data of 130 Japanese pediatric acute myeloid leukemia (AML) patients,
      we found that EVI1 and MEL1 were overexpressed in ~30% of patients without
      obvious translocations of these gene loci, and that their high expression was
      significantly associated with inferior survival. High EVI1 expression was
      detected mainly in myelomonocytic-lineage (designated as e-M4/M5 subtype)
      leukemia with MLL rearrangements and in megakaryocytic-lineage (designated as e
      M7 subtype) leukemia, and its prognostic association was observed in the e-M4/M5
      subtype but not in the e-M7 subtype. On the other hand, high MEL1 expression was
      detected in myelocytic-lineage (designated as e-M0/M1/M2 subtype) and e-M4/M5
      subtype leukemia without MLL rearrangements, and its prognostic association was
      independent from the subtypes. Because of their subtype-dependent and mutually
      exclusive expression, a combined evaluation of their high expression enabled a
      clear distinction of patients with inferior survival (P<0.00001 in event-free
      survival (EFS) and overall survival (OS)). This association was confirmed by
      quantitative reverse transcription PCR analysis of an independent cohort of 81
      patients (P=0.00017 in EFS, P=0.00028 in OS). We propose that the combined
      estimation of EVI1 and MEL1 expression will be an effective method to predict the
      prognosis of pediatric AML. 

PMID- 25567133
TI  - The predominant myeloma clone at diagnosis, CDR3 defined, is constantly
      detectable across all stages of disease evolution.

PMID- 25567134
TI  - Allelic imbalance in CALR somatic mutagenesis.

PMID- 25567136
TI  - Elevated serum sCD23 and sCD30 up to two decades prior to diagnosis associated
      with increased risk of non-Hodgkin lymphoma.

PMID- 25567138
TI  - How should "hot" players in basketball be defended? The use of fast-and-frugal
      heuristics by basketball coaches and players in response to streakiness.
AB  - Previous research has shown that changes in shot difficulty may have rendered the
      hot-hand effect in basketball unobservable and are potentially a result of
      defensive adjustments. However, it has not been directly analysed whether
      strategic changes indeed take place in response to streakiness and whether they
      are effective with respect to winning games. The current work consists of an
      experimental study with 18 professional coaches and 20 players based on video
      sequences from National Basketball Association games, where the shown player
      displayed a streaky performance in half of the sequences. While coaches were
      asked to devise a defensive strategy after each viewed sequence, players had to
      assume the role of the shown player and decide whether to shoot or pass the ball.
      We find that coaches tended to increase the defensive pressure significantly more
      often on presumably hot players and thus make use of the hot-hand heuristic.
      Meanwhile, players chose to shoot more frequently in low-pressure and streaky
      situations but selected "pass" regardless of the previous performance when they
      faced increased defensive pressure. Assuming that a streaky player's performance
      is indeed elevated during hot phases, hot-hand behaviour can be considered
      adaptive in certain situations as it led hot players to pass instead of shoot. 

PMID- 25567137
TI  - Involvement of double-stranded RNA-dependent protein kinase and antisense viral
      RNA in the constitutive NFkappaB activation in adult T-cell leukemia/lymphoma
      cells.

PMID- 25567135
TI  - Molecular profiling of myeloid progenitor cells in multi-mutated advanced
      systemic mastocytosis identifies KIT D816V as a distinct and late event.
AB  - To explore the molecular profile and its prognostic implication in systemic
      mastocytosis (SM), we analyzed the mutation status of granulocyte-macrophage
      colony-forming progenitor cells (CFU-GM) in patients with KIT D816V(+) indolent
      SM (ISM, n=4), smoldering SM (SSM, n=2), aggressive SM (ASM, n=1), SM with
      associated clonal hematologic non-mast cell lineage disorder (SM-AHNMD, n=5) and
      ASM-AHNMD (n=7). All patients with (A)SM-AHNMD (n=12) carried 1-4 (median 3)
      additional mutations in 11 genes tested, most frequently TET2, SRSF2, ASXL1, CBL
      and EZH2. In multi-mutated (A)SM-AHNMD, KIT D816V(+) single-cell-derived CFU-GM
      colonies were identified in 8/12 patients (median 60%, range 0-95). Additional
      mutations were identified in CFU-GM colonies in all patients, and logical
      hierarchy analysis indicated that mutations in TET2, SRSF2 and ASXL1 preceded KIT
      D816V. In ISM/SSM, no additional mutations were detected and CFU-GM colonies were
      exclusively KIT D816V(-). These data indicate that (a) (A)SM-AHNMD is a multi
      mutated neoplasm, (b) mutations in TET2, SRSF2 or ASXL1 precede KIT D816V in ASM
      AHNMD, 

PMID- 25567139
TI  - Evaluation of antimicrobial resistance of Campylobacter spp. isolated from
      broiler carcasses.
AB  - 1. The aim of the present study was to evaluate the antimicrobial resistance of
      Campylobacter strains (C. jejuni, C. coli and C. lari) isolated from broiler
      carcasses processed in the State of Parana, Brazil. 2. Rates of microbial
      resistance and susceptibility were assessed by both Disk Diffusion (DD) and Etest
      (Minimum Inhibitory Concentration) techniques. Antibiotics were tested using DD
      (12 antibiotics) and/or MIC (7 antibiotics) methods. 3. A total of 95.8% of the
      strains were resistant to at least two agents. In terms of multidrug resistance,
      75% of strains were resistant to three or more groups of antibiotics. The highest
      rates of resistance were detected for cefalotin, ciprofloxacin, tetracycline and
      nalidixic acid. A high rate of susceptibility of the strains to erythromycin
      (95.8%) was found confirming that this is considered the agent of choice for
      treating campylobacteriosis. Comparison of the microbial resistance and
      susceptibility, as determined simultaneously by the two methods, found the
      techniques to be statistically equivalent for 5 out of the 6 antibiotics tested.
      4. The results of this study suggest the need for adopting measures to control
      the use of antibiotics in broiler production to prevent multidrug resistance of
      Campylobacter strains and reduce the risk of serious human diseases caused by the
      consumption of contaminated chicken meat. 

PMID- 25567140
TI  - 'If you are circumcised, you are the best': understandings and perceptions of
      voluntary medical male circumcision among men from KwaZulu-Natal, South Africa.
AB  - While the uptake of voluntary medical male circumcision (VMMC) is increasing,
      South Africa has only attained 20% of its target to circumcise 80% of adult men
      by 2015. Understanding the factors influencing uptake is essential to meeting
      these targets. This qualitative study reports on findings from focus-group
      discussions with men in rural KwaZulu-Natal, South Africa, about what factors
      influence their perceptions of VMMC. The study found that VMMC is linked to
      perceptions of masculinity and male gender identity including sexual health,
      sexual performance and pleasure, possible risk compensation and self-identity.
      Findings highlight the need to understand how these perceptions of sexual health
      and performance affect men's decisions to undergo circumcision and the
      implications for uptake of VMMC. The study also highlights the need for
      individualised and contextualised information and counselling that can identify,
      understand and address the perceptions men have of VMMC, and the impacts they
      believe it will have on them. 

PMID- 25567141
TI  - A growth model for directed complex networks with power-law shape in the out
      degree distribution.
AB  - Many growth models have been published to model the behavior of real complex
      networks. These models are able to reproduce several of the topological
      properties of such networks. However, in most of these growth models, the number
      of outgoing links (i.e., out-degree) of nodes added to the network is constant,
      that is all nodes in the network are born with the same number of outgoing links.
      In other models, the resultant out-degree distribution decays as a poisson or an
      exponential distribution. However, it has been found that in real complex
      networks, the out-degree distribution decays as a power-law. In order to obtain
      out-degree distribution with power-law behavior some models have been proposed.
      This work introduces a new model that allows to obtain out-degree distributions
      that decay as a power-law with an exponent in the range from 0 to 1. 

PMID- 25567142
TI  - Prioritization of active antimalarials using structural interaction profile of
      Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR)-triclosan
      derivatives.
AB  - An empirical relationship between the experimental inhibitory activities of
      triclosan derivatives and its computationally predicted Plasmodium falciparum
      enoyl-acyl carrier protein (ACP) reductase (PfENR) dock poses was developed to
      model activities of known antimalarials. A statistical model was developed using
      57 triclosan derivatives with significant measures (r = 0.849, q(2) = 0.619, s =
      0.481) and applied on structurally related and structurally diverse external
      datasets. A substructure-based search on ChEMBL malaria dataset (280 compounds)
      yielded only two molecules with significant docking energy, whereas eight active
      antimalarials (EC(50) < 100 nM, tested on 3D7 strain) with better predicted
      activities (pIC(50) ~ 7) from Open Access Malaria Box (400 compounds) were
      prioritized. Further, calculations on the structurally diverse rhodanine
      molecules (known PfENR inhibitors) distinguished actives (experimental IC(50) =
      0.035 MUM; predicted pIC(50) = 6.568) and inactives (experimental IC(50) = 50
      MUM; predicted pIC50 = -4.078), which showed that antimalarials possessing dock
      poses similar to experimental interaction profiles can be used as leads to test
      experimentally on enzyme assays.

PMID- 25567144
TI  - [More attention to diagnostic accuracy of dizziness and vertigo].

PMID- 25567143
TI  - Gelatin-based particulate systems in ocular drug delivery.
AB  - Despite all scientists efforts exerted over the past years, the ocular delivery
      of drugs remains a great challenge due to several barriers and hurdles faced by
      this kind of administration. The exploitation of gelatin that has a long history
      of safe use in pharmaceuticals and which is considered as a GRAS (Generally
      Regarded As Safe) material by the FDA was not fully achieved in this field. This
      review summarizes the recent studies and findings where gelatin-based micro- and
      nanoparticles were used for successful ocular delivery aiming at drawing the
      attention of researchers and scientists to this valuable biomaterial that has not
      been fully explored. 

PMID- 25567145
TI  - [Management of bilateral benign paroxysmal positional vertigo with Dix-Hallpike
      test].
AB  - OBJECTIVE: To explore the diagnosis and treatment of benign paroxysmal positional
      vertigo (BPPV) with bilateral positive Dix-Hallpike test. METHODS: This is a
      retrospective study based on the clinical data of BPPV patients diagnosed in the
      Dizziness Clinic of Changzheng Hospital from January 2012 to December 2012.
      Totally 490 patients with vertigo and nystagmus provoked by Dix-Hallpike maneuver
      were included in the present analysis. RESULTS: Among all the patients, 55
      (11.2%) of them presented with bilateral nystagmus by the provocative test.
      According to the type of nystagmus provoked by Dix-Hallpike maneuver, the 55
      patients can be divided into the following four categories. (1) Bilateral
      geotropic (n = 16) and apogeotropic nystagmus (n = 5): all these patients were
      diagnosed with horizontal canal BPPV and free of vertigo after head side-shaking
      exercise in supine position and Barbecue maneuver. (2) Bilateral predominant down
      beating nystagmus (n = 2): patients in this group were diagnosed with anterior
      canal BPPV, and got recovered after Kim maneuver. (3) Bilateral torsional up
      beating geotropic nystagmus (n = 20): after a lying-down test, 6 of the patients
      manifested as vertical up-beating nystagmus and 14 patients remained torsional up
      beating nystagmus. The former were diagnosed with bilateral posterior canal BPPV,
      and were cured after bilateral PRM therapy, and the latter were diagnosed with
      horizontal canal BPPV, who were cured after Barbecue maneuver. (4) Torsional up
      beating geotropic nystagmus on one side and down-beating nystagmus on the other
      side (n = 12). The down-beating nystagmus on the other side disappeared when the
      patients was firstly seated up with head down in 30 degrees for half an hour
      before second Dix-Hallpike maneuver. These patients were diagnosed with
      unilateral posterior canal BPPV and cured by PRM therapy. CONCLUSIONS: It is
      common for vertigo patients with bilateral nystagmus induced by Dix-Hallpike
      test. The diagnoses should be made by the types of nystagmus provoked step by
      step before maneuver therapy.

PMID- 25567146
TI  - [An analysis of clinical features and therapies of patients with psychogenic
      dizziness].
AB  - OBJECTIVE: To accumulate clinical experience and to direct clinical work.
      METHODS: A total of 208 patients with psychogenic dizziness from department of
      neurology of Navy General Hospital of PLA were included in the study. Self-rating
      anxiety scale (SAS), self-rating depression scale (SDS) and Bech-Rafaelsen mania
      rating scale (BRMS) were used for the evaluation. RESULTS: Among all the patients
      aged from 17 to 77 (the average age: 52), 152 were female and 56 were male. There
      were 3 types according to different clinical features and therapy prognosis:
      anxiety and depression type (176 cases, 84.6%) , hysteria type (18 cases, 8.7%)
      and mania type (14 cases, 6.7%) . The drugs increasing the concentration of
      excitatory had a good therapeutic efficacy on anxiety and depression type.
      Alluding cure had notable effect on hysteria type and mood stabilizer had notable
      effect on mania type. CONCLUSIONS: Women tended to have psychogenic dizziness. It
      can be divided into three types: anxiety and depression type, hysteria type and
      mania type. Clinical symptoms and laboratory examination of each type have their
      own characteristics, and treatment strategies are also different.

PMID- 25567147
TI  - [The contributing risk factors, prevention and treatment of functional dependence
      among the oldest-old and elderly subjects].
AB  - OBJECTIVE: To compare the risk factors on the functional dependence between the
      oldest-old and elderly veterans. METHODS: A cross-sectional survey was conducted
      among veterans ( >= 60 years of age) lived in 44 veterans' communities in
      Beijing. The socio-demographic information and history of non-communicable
      chronic diseases were collected via face-to-face interviews, and the functional
      status was assessed by the 20-item version of the Activities of Daily Living
      Scale. RESULTS: The risk factors associated with increased hazard of the
      functional dependence in the oldest-old ( >= 80 years old) were cognitive
      impairment, extrapyramidal diseases, cerebral infarction, transient ischemic
      attack, sleep disorders, hypnotics, osteoarthrosis, hypertension and fall with
      the odds ratio (OR) of 1.241-2.962 (all P < 0.05). Stroke, depression, cognitive
      impairment, extrapyramidal diseases, sleep disorders, hypnotics, fall,
      cardiovascular diseases, osteoarthrosis and hearing loss were the risk factors
      for that in the elderly subjects (aged 60-79 years). The OR was 1.232-5.790 (all
      P < 0.05). However, avocational activities such as social activity, physical
      exercise, photography, reading and games, decreased the risk of functional
      dependence in both the oldest-old and elderly people. CONCLUSIONS:
      Neuropsychiatric disorders are the leading causes contributed to the functional
      dependence among oldest-old and elderly population. Neurodegenerative diseases in
      the oldest-old, stroke and depression in elderly people should be the priorities
      in ameliorating disability. Healthy lifestyle and avocational activities could
      improve the functional status of the oldest-old and elderly population.

PMID- 25567148
TI  - [The value of corneal confocal microscopy in diagnosing early small fibre
      neuropathy].
AB  - OBJECTIVE: To explore the diagnostic value of corneal confocal microscopy in the
      early small fibre neuropathy (SFN). METHODS: A total of 45 patients with small
      fibre neuropathy and 50 age-matched healthy subjects undertook a neurological
      evaluation, neurological deficits score (NDS), sural nerve conduction velocity,
      contact heat evoked potential (CHEP) and corneal confocal microscopy (CCM) to
      quantify small nerve fibre pathology. Four parameters including nerve fiber
      length (NFL), nerve branch density (NBD), nerve fiber density (NFD) and nerve
      fibre tortuosity (NFT) were calculated from the observation of corneal confocal
      microscopy. RESULTS: Compared with the control group, significantly decreased NFD
      and NBD were found in the SFN group [ (42.00 +/- 25.26)/mm(2) vs (72.38 +/-
      14.09)/mm(2) ;(31.93 +/- 13.21)/mm(2) vs (46.24 +/- 11.48)/mm(2); with all P <
      0.05], while NFT were significantly increased in the SFN group [(2.48 +/- 0.87)
      levels vs (0.88 +/- 0.56) levels, P < 0.001]. The neurological deficits score was
      correlated with NFT, NFD and NBD (r = 0.782, -0.376, -0.504; with all P < 0.001).
      CONCLUSION: CCM is a new and sensitive noninvasive clinical technique that may be
      used to detect early small fibre nerve damage in patients with SFN.

PMID- 25567149
TI  - [A correlation study between serum direct bilirubin and lipid in type 2 diabetic
      patients].
AB  - OBJECTIVE: To investigate the association between DBil with normal range and
      serum lipid in type 2 diabetic patients. METHODS: A total of 979 subjects with
      type 2 diabetes admitted to the Department of Endocrinology of Chinese PLA
      General Hospital from June 2012 to June 2013 were included for the study. Serum
      DBil, TC, TG, HDL-C and LDL-C levels were collected for the analyses. Subjects
      were divided into four groups based on the DBil levels: Q1 group (<2.2 umol/L),
      Q2 group (2.2-< 2.9 umol/L), Q3 group (2.9-< 3.9 umol/L) and Q4 group ( >= 3.9
      umol/L) . RESULTS: (1) TC, TG, LDL-C levels were significantly lower in Q4 group
      than those in the other three Q groups after adjustment of age, gender, duration
      of diabetes, BMI, smoking, drinking, glycosylated hemoglobin A1c (HbA1c) ,
      fasting plasma glucose (FPG), medication, ALT, AST and fatty liver. No difference
      could be viewed in HDL-C level between each group (P = 0.65). (2) Pearson
      correlation analyses showed that DBil was inversely correlated with TC (r = 
      0.33, P < 0.01), TG (r = -0.23, P < 0.01), LDL-C (r = -0.18, P < 0.01), and
      positively correlated with HDL-C level in men (r = 0.14, P < 0.01), respectively.
      Multiple linear regression analyses showed DBil was an independent impact factor
      for TC, TG and LDL-C. (3) Compared with Q1 group, the odds ratio (OR) for
      dyslipidemia was 0.54 (95%CI 0.35-0.82, P < 0.01), 0.56 (95%CI 0.37-0.85, P <
      0.01) and 0.44 (95%CI 0.29-0.69, P < 0.01) in Q2, Q3 and Q4 group, respectively,
      after age, gender, duration of diabetes, BMI, smoking, drinking, HbA1c, FPG,
      medication, ALT, AST and fatty liver were adjusted. Moreover, the OR for
      dyslipidemia was much lower in Q4 man subjects with age<55 years , HbA1c >= 6.5%,
      BMI<25 kg/m(2), and with no fatty liver. CONCLUSION: DBil in normal range was
      closely associated with lipid profile in type 2 diabetes. It might play a
      protective effect in dyslipidemia.

PMID- 25567150
TI  - [The effects of olmesartan on ambulatory blood pressures and blood pressure
      variability in patients with mild to moderate essential hypertension].
AB  - OBJECTIVE: To evaluate the effect of olmesartan medoxomil tablets (olmesartan) in
      comparison with Olmetec on 24 h ambulatory blood pressure (ABPM) and blood
      pressure variability (BPV) in patients with mild to moderate hypertension.
      METHODS: A randomized, double-blind, double-mimic controlled trial was
      performed.Forty-eight patients with mild to moderate essential hypertension were
      randomly into treatment group (olmesartan) and control group (Olmetec) for eight
      weeks. The ABPM was taken before and at the end of the trial. RESULTS: After
      eight weeks, treatment with olmesartan induced a significant reduction in ABPM in
      patients [(9 +/- 3)/(11 +/- 3) mmHg(1 mmHg = 0.133 kPa)], which is similar with
      the reduction by Olmetec [(9 +/- 4)/(9 +/- 5) mmHg], P > 0.05. This situation
      holds for BPV with the standard deviations of 24 h, systolic blood
      pressure/diastolic blood pressure of pre-treatment and pro-treatment were (10 +/-
      2)/(11 +/- 3) mmHg vs (10 +/- 3)/(12 +/- 2) mmHg in olmesartan group, and (10 +/-
      3)/(11 +/- 3) mmHg vs (12 +/- 3)/(12 +/- 4) mmHg in Olmetec group. (3) There is
      no difference in the rate of adverse event between olmesartan (10.42%) and
      Olmetec (8.33%) treatment (P > 0.05). CONCLUSION: Similar to Olmetec, treatment
      with olmesartan once daily can significantly reduce ABPM in patients with mild to
      moderate essential hypertension.

PMID- 25567151
TI  - [The effects of Peking Union Medical College Hospital Critical Ultrasonic
      Management scheme on the etiological diagnosis of dyspnea and/or hemodynamic
      instability in ICU patients].
AB  - OBJECTIVE: To investigate the effects of Peking Union Medical College Hospital
      (PUMCH) Critical Ultrasonic Management (PCUM) scheme on the etiological diagnosis
      and treatment decisions for the patients with dyspnea and/or hemodynamic
      instability in ICU. METHODS: Patients who suffered from dyspnea and/or
      hemodynamic instability in PUMCH ICU were included in this study. The time to
      preliminary diagnosis, time to final diagnosis, diagnostic accuracy, time to
      accurate treatment, time to consultation with other specialties, time to other
      examinations were recorded. RESULTS: A total of 129 patients were included in
      this study. In patients applied with PCUM scheme, time to preliminary diagnosis,
      final diagnosis and accurate treatment were (15 +/- 6)min, (65 +/- 16)min and (34
      +/- 14)min respectively, and the accuracy of diagnosis was 93.0%. PCUM patients
      had high sensitivity and specificity for the diagnosis of acute respiratory
      distress syndrome (ARDS)(sensitivity 90.2%/specificity 93.6%), distributive
      shock(sensitivity 92.5%/specificity 93.6%) and pulmonary edema(sensitivity
      93.4%/specificity 92.7%) etc. CONCLUSIONS: The PCUM scheme is associated with
      short time to preliminary diagnosis and high diagnostic accuracy and could
      improve the treatment for patients with dyspnea and/or hemodynamic instability.

PMID- 25567152
TI  - [The associations of ulcerative colitis with vascular endothelial growth factor (
      2578C/A) and (+936C/T) single nucleotide polymorphisms].
AB  - OBJECTIVE: To investigate the association of (-2578C/A) and (+936C/T) single
      nucleotide polymorphism(SNPs) of vascular endothelial growth factor (VEGF) gene
      with the susceptibility to ulcerative colitis (UC). METHODS: A total of 373 UC
      patients and 503 healthy controls were recruited. The (-2578C/A) and (+936C/T)
      polymorphism of VEGF gene were detected using a mini-sequencing technique.
      RESULTS: By an unconditional logistic regression analysis, the frequencies of the
      mutant allele T and genotype CT+TT of VEGF gene (+936C/T) were significantly
      decreased in patients with severe UC compared to the controls (10.4% vs 19.3%, OR
      = 0.487, 95%CI 0.248-0.954, P = 0.036; 18.8% vs 33.8%, OR = 0.452, 95%CI 0.214
      0.955, P = 0.037, respectively). Moreover, patients with severe UC had
      significant lower rates of mutant allele T and genotype CT+TT compared with
      patients with mild and moderate UC (10.4% vs 20.5%, OR = 0.452, 95%CI 0.229
      0.894, P = 0.022; 18.8% vs 36.9%, OR = 0.394, 95%CI 0.185-0.842, P = 0.016,
      respectively). The frequencies of mutant allele A and genotype CA+AA of VEGF (
      2578C/A) gene were not statistically different between UC patients and the
      controls. Moreover, they were not significantly associated with the
      clinicopathologic features in UC patients. CONCLUSIONS: The mutation of VEGF
      (+936C/T) gene is correlated with the severity of UC. However, the polymorphism
      of VEGF (-2578C/A) gene is not significantly related to the susceptibility to UC.

PMID- 25567153
TI  - [Losartan modulates T helper type 1 cells and T helper type 17 cells-mediated
      responses in a mouse model of lipopolysaccharide-induced acute lung injury].
AB  - OBJECTIVE: To assess the effect of losartan, angiotensin II receptor type 1 (AT1)
      receptor antagonist, on the pulmonary T helper (Th) cell polarization response in
      acute lung injury (ALI) mice. METHODS: C57BL/6 mice were randomized into control
      group, ALI group and ALI + losartan group, which respectively were administrated
      with phosphate buffered saline(PBS), 2 mg/kg lipopolysaccharide (LPS) and 2 mg/kg
      LPS as well as 15 mg/kg losartan 30 minutes before intratracheal injection of
      LPS. Lung wet weight/body weight (LW/BW) was recorded to assess the severity of
      lung injury. The mRNA expression levels of T-box expressed in T cells (T-bet),
      GATA-binding protein-3 (GATA-3) and retinoid-related orphan nuclear receptor
      gammat (RORgammat) were quantitatively measured by real-time polymerase chain
      reaction (RT-PCR). Meanwhile, interleukin 6(IL-6), interferon gamma (IFNgamma) ,
      IL-4 and IL-17 in lung homogenates were assessed by enzyme-linked immunosorbent
      assay (ELISA). RESULTS: (1) LW/BW was significantly increased in ALI group
      compared with ALI+losartan group. (2) Histologically, widespread interstitial
      thickening with edema, severe alveolar hemorrhage, and diffuse interstitial
      infiltration of inflammatory cells were observed in the ALI group. Whereas,
      losartan effectively attenuated the LPS-induced alveolar hemorrhage and leukocyte
      infiltration. (3) The levels of IL-6 in lung tissue were significantly enhanced
      in the LPS-induced ALI mice, while it markedly decreased in ALI +losartan group.
      (4) The mRNA expression of T-bet and RORgammat was up-regulated in ALI mice at 24
      h and 48 h compared to control group (P < 0.05). There was no significant
      difference in the expression of GATA-3. In addition, compared with ALI group, ALI
      mice with pretreatment of losartan resulted in significantly reduced mRNA
      expression of T-bet at 24 h and 48 h and RORgammat mRNA expression at 48 h (all P
      < 0.05). (5) Meanwhile, the levels of IFNgamma, IL-4, IL-17 and IL-6 in lung
      tissue were significantly enhanced at 24 h and 48 h in the LPS-induced ALI mice.
      In addition, both IFNgamma and IL-17 in lung tissue at 24 h and 48 h decreased
      significantly in losartan-pretreated mice compared with the ALI mice. However,
      the level of IL-4 in lungs was similar in ALI group and ALI+losartan group.
      CONCLUSIONS: Losartan has a protective effect on LPS-induced ALI, which may be
      partly dependent on suppressions of Th1 and Th17 polarization response.

PMID- 25567154
TI  - Anxious and depressive avoidance behavior in post-loss psychopathology: a
      longitudinal study.
AB  - BACKGROUND: Avoidance behavior is a central component of cognitive behavioral
      theories of bereavement-related psychopathology. Yet, its role is still not well
      understood. This study examined associations of anxious and depressive avoidance
      behaviors with concurrently and prospectively assessed symptom-levels of
      prolonged grief disorder (PGD), depression, and posttraumatic stress disorder
      (PTSD). DESIGN AND METHODS: Two hundred and ninety-one individuals, confronted
      with loss maximally three years earlier, completed self-report measures of
      anxious and depressive avoidance and emotional distress and again completed
      distress measures one year later. RESULTS: Anxious and depressive avoidance were
      concurrently associated with symptom-levels of PGD, depression, and PTSD, even
      when controlling for the shared variance between both forms of avoidance and
      relevant socio-demographic and loss-related variables. Prospective analyses
      showed that baseline anxious avoidance predicted increased symptom-levels of PGD,
      depression, and PTSD one year later, among participants who were in their first
      year of bereavement but not among those who were beyond this first year. Baseline
      depressive avoidance was significantly associated with elevated PTSD one year
      later, irrespective of time since loss. CONCLUSIONS: Both anxious and depressive
      avoidance are associated with different indices of poor long-term adjustment
      following loss. However, anxious avoidance seems primarily detrimental in the
      first year of bereavement.

PMID- 25567155
TI  - Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing
      prothrombin complex concentrates and idarucizumab.
AB  - Urgent surgery or life-threatening bleeding requires prompt reversal of the
      anticoagulant effects of dabigatran. This study assessed the ability of three-
      and four-factor prothrombin complex concentrate (PCC) and idarucizumab (specific
      antidote for dabigatran) to reverse the anticoagulant effects of dabigatran in a
      porcine model of trauma. Twelve animals were given dabigatran etexilate (DE)
      orally and dabigatran intravenously, before infliction of trauma. Six animals
      received tranexamic acid plus fibrinogen concentrate 12 minutes post-injury. Six
      PCCs (each 30 and 60 U/kg) and idarucizumab (30 and 60 mg/kg) were added to blood
      samples ex vivo. Coagulation was assessed by several coagulation assays. All
      coagulation parameters were altered after dabigatran infusion (plasma level: 442
      +/- 138 ng/ml). Both three- and four-factor PCCs mostly or completely reversed
      the effects of dabigatran on thromboelastometry variables and PT but not on aPTT.
      Idarucizumab neutralised plasma concentrations of dabigatran, and reversed the
      effects of the drug on coagulation variables. Thrombin generation showed dose
      dependent over-correction following the addition of PCC, implying that elevated
      levels of thrombin are required to overcome dabigatran-induced coagulopathy. In
      contrast, treatment with idarucizumab returned thrombin generation to baseline
      levels. Following trauma, therapy with tranexamic acid plus fibrinogen improved
      correction of coagulation parameters by PCC, and thromboelastometry parameters by
      idarucizumab. All investigated PCCs improved dabigatran- and trauma-induced
      coagulopathy to a similar degree. In conclusion, this study shows that three- and
      four-factor PCCs are similarly effective for dabigatran reversal. Idarucizumab
      also reversed the effects of dabigatran and, unlike PCCs, was not associated with
      over-correction of thrombin generation. 

PMID- 25567156
TI  - Case of accelerated silicosis in a sandblaster.
AB  - Sandblasting is traditionally known as a high-risk profession for potential
      development of lung silicosis. Reported is a case of a sandblaster with confirmed
      accelerated silicosis, a condition rather rarely diagnosed in the Czech Republic.
      Initially, the patient presented with progressive dry cough and exertional
      dyspnoea. In the early diagnostic process, a possible occupational aetiology was
      considered given his occupational history and known high-risk exposure to
      respirable silica particles confirmed by industrial hygiene assessment at the
      patient's workplace. The condition was confirmed by clinical, histological and
      autopsy findings. The patient died during lung transplantation, less than five
      years from diagnosis. 

PMID- 25567157
TI  - Editor's note: Say "Yes!" to NO.

PMID- 25567158
TI  - The gift of medicine.

PMID- 25567161
TI  - In reply to Skrobala and Malicki.

PMID- 25567163
TI  - ACG presidential introduction.

PMID- 25567160
TI  - Application of failure mode and effects analysis to intracranial stereotactic
      radiation surgery by linear accelerator: In regard to Masini et al.

PMID- 25567159
TI  - Active Breathing Coordinator reduces radiation dose to the heart and preserves
      local control in patients with left breast cancer: report of a prospective trial.
AB  - PURPOSE: Incidental radiation dose to the heart and lung during breast radiation
      therapy (RT) has been associated with an increased risk of cardiopulmonary
      morbidity. We conducted a prospective trial to determine if RT with the Active
      Breathing Coordinator (ABC) can reduce the mean heart dose (MHD) by >=20% and
      dose to the lung. METHODS AND MATERIALS: Patients with stages 0-III left breast
      cancer (LBC) were enrolled and underwent simulation with both free breathing (FB)
      and ABC for comparison of dosimetry. ABC was used during the patient's RT course
      if the MHD was reduced by >=5%. The median prescription dose was 50.4 Gy plus a
      boost in 77 patients (90%). The primary endpoint was the magnitude of MHD
      reduction when comparing ABC to FB. Secondary endpoints included dose reduction
      to the heart and lung, procedural success rate, and adverse events. RESULTS: A
      total of 112 patients with LBC were enrolled from 2002 to 2011 and 86 eligible
      patients underwent both FB and ABC simulation. Ultimately, 81 patients received
      RT using ABC, corresponding to 72% procedural success. The primary endpoint was
      achieved as use of ABC reduced MHD by 20% or greater in 88% of patients (P <
      .0001). The median values for absolute and relative reduction in MHD were 1.7 Gy
      and 62%, respectively. RT with ABC provided a statistically significant dose
      reduction to the left lung. After a median follow up of 81 months, 8-year
      estimates of locoregional relapse, disease-free, and overall survival were 7%,
      90%, and 96%, respectively. CONCLUSIONS: ABC was well tolerated and significantly
      reduced MHD while preserving local control. Use of the ABC device during RT
      should be considered to reduce the risk of ischemic heart disease in populations
      at risk.

PMID- 25567164
TI  - The American College of Gastroenterology: your professional home past, present,
      and future.

PMID- 25567165
TI  - Image of the month: A rare cause of obstructive jaundice in a postpartum woman.

PMID- 25567166
TI  - Video of the month: Actively bleeding idiopathic vascular bleb found via double
      balloon enteroscopy.

PMID- 25567171
TI  - Trouble in Paris (classification): polyp morphology is in the eye of the
      beholder.
AB  - Key challenges to colonoscopy outcomes include polyp detection, appropriate polyp
      resection, and prediction of recurrent polyps. The Paris classification of
      gastrointestinal neoplasia has been used to attempt to address these challenges
      based on the hypothesis that the visual appearance of a polyp (e.g., sessile,
      flat, depressed) has an impact on these outcomes. Although the Paris
      classification has been widely used as a measurement tool in research, and
      reported to predict outcomes such as risk for high-grade dysplasia and invasive
      carcinoma, interobserver variability associated with this classification scheme
      has not been studied. In the current issue of the Red Journal, van Doorn et al.
      studied the interobserver variation of Paris classification in 85 colorectal
      polyps assessed by seven expert colonoscopists. They found that interobserver
      variation measured by kappa was only moderate (kappa=0.42; 95% confidence
      interval: 0.39-0.45). These findings suggest that without methods to improve
      interobserver variability, the Paris classification cannot routinely be used for
      research or routine practice. New approaches to characterizing polyp appearance
      may be required to use morphology as a predictor of clinical outcomes. 

PMID- 25567172
TI  - Guidelines on genetic evaluation and management of Lynch syndrome.

PMID- 25567173
TI  - Chromoendoscopy with iodine staining, as well as narrow-band imaging, is still
      useful and reliable for screening of early esophageal squamous cell carcinoma.

PMID- 25567174
TI  - Response to Dinjens et al.

PMID- 25567175
TI  - Response to Shimizu et al.

PMID- 25567176
TI  - Re: Influence of previous night call and sleep deprivation on screening
      colonoscopy quality.

PMID- 25567177
TI  - Response to Yarze.

PMID- 25567178
TI  - The use of transarterial chemoembolization in hepatiocellular carcinoma 2 cm or
      smaller.

PMID- 25567179
TI  - Response to Lo.

PMID- 25567180
TI  - New strategies immediately needed for molecular marker reporting in colorectal
      cancer.

PMID- 25567181
TI  - Understanding the biologic behavior of sessile serrated adenomas/polyps.

PMID- 25567182
TI  - "Are you a gastroenterologist or a philosopher?".

PMID- 25567183
TI  - Does TMPRSS6 RS855791 polymorphism contribute to iron deficiency in treated
      celiac disease?

PMID- 25567184
TI  - Awareness of tract seeding with endoscopic ultrasound tissue acquisition in
      perihilar cholangiocarcinoma.

PMID- 25567188
TI  - The effects of RNA interference targeting Bactrocera dorsalis ds-Bdrpl19 on the
      gene expression of rpl19 in non-target insects.
AB  - Double-stranded RNA (dsRNA) designed to target pest genes emerges as a promising
      strategy for improving pest control. Therefore, it is necessary to assess the
      effects of dsRNA on non-target insects, such as native enemies and beneficial
      insects, to determine the environmental safety of such treatments. In this paper,
      we investigated the effects of dsRNA targeting rpl19 from Bactrocera dorsalis on
      non-target insects in citrus ecological systems by feeding the dsRNA to
      Bactrocera minax, Apis mellifera and Diachasmimorpha longicaudata. The results
      showed that when B. dorsalis were fed rpl19 CDS dsRNA or 3'UTR dsRNA, the
      expression of rpl19 was dramatically decreased. Feeding the Bdrpl19 CDS dsRNA to
      adult B. minax and D. longicaudata caused their respective rpl19 genes to be
      knocked down over 50-70 and 40%, respectively, but it had no effect on the
      expression of the rpl19 gene in A. mellifera. The Bdrpl19 3'UTR dsRNA did not
      have any silencing effects on the expression levels of rpl19 in non-target
      insects. This study provides evidence that dsRNA can impact non-target organisms,
      but the 3'UTR dsRNA may not have effects in non-target organisms.

PMID- 25567189
TI  - The impact of management strategies in apple orchards on the structural and
      functional diversity of epigeal spiders.
AB  - Apple orchards are agro-ecosystems managed with high levels of inputs and
      especially pesticides. Epigeal spider communities were sampled in three seasons
      using pitfall traps in 19 apple orchards with four different management
      strategies (abandoned, under organic, Integrated Pest Management or conventional
      protection) and thus significantly different pesticide usage. The abundance and
      diversity of the spider communities was the highest in abandoned orchards. Higher
      diversity and evenness values were the only difference in spider communities from
      the organic orchards compared to the other commercial orchards. The analysis of
      five ecological traits (proportion of aeronauts, type of diet, overwintering
      stages, body size and maternal care), however, clearly showed differences in the
      spiders from the organic orchards. The spider species in the other commercial
      orchards were smaller and have higher dispersal abilities. Seven bioindicator
      species were identified in abandoned orchards, two species in organic ones (only
      Lycosidae) and one species in conventional orchards (Linyphiidae). 

PMID- 25567192
TI  - Pharmacokinetic interaction between Kaempferia parviflora extract and sildenafil
      in rats.
AB  - Kaempferia parviflora (KP) is a plant widely used in Southeast Asia. Its major
      compounds are 3,5,7,3',4'-pentamethoxyflavone (PMF), 5,7,4'-trimethoxylflavone
      (TMF), and 5,7-dimethoxyflavone (DMF). This study investigated the effect of KP
      extract on the blood levels and pharmacokinetics of sildenafil co-administration
      in rats. Rats were randomly assigned to four groups. Groups 1, 2, and 3 were
      given sildenafil 20 mg/kg daily for 9 days. On days 4-9 of each treatment period,
      the treated rats received KP extract (250 mg/kg) and vehicle (groups 2 and 3,
      respectively). Group 4 received KP extract only (250 mg/kg daily for 9 days).
      Daily blood concentrations of sildenafil, PMF, TMF, and DMF were determined by
      HPLC to evaluate the daily blood level interactions. Additional blood samples
      were collected at various times on the last day of treatment to evaluate the
      pharmacokinetic interactions. The KP extract decreased blood levels of sildenafil
      on the first day of co-administration by 95 % but the percentage reduction was
      insignificant on subsequent days. When co-administered with KP extract, the area
      under the curve (AUC), maximum concentration (C max), and half-life (T 1/2) of
      sildenafil were decreased by 60-65, 40-52, and 32-54 %, respectively, with the
      elimination rate constant (K e) increased by 37-77 %. In addition, PMF, TMF, and
      DMF concentrations and their AUC, C max, T max, K e, and T 1/2 values were
      changed after co-administration of KP extract and sildenafil. 

PMID- 25567191
TI  - Changes in the spectral pattern of selenium accumulation in Coleus blumei and the
      effects of chelation.
AB  - Chemically enhanced phytoremediation has been proposed as an effective approach
      to remove heavy metals from contaminated soil through the use of high biomass
      production plants. This study investigated changes in the spectral pattern of
      selenium (Se) accumulation in Coleus blumei Benth. (coleus) plants grown in
      hydroponics with 1.0 mg/l sodium selenite (Na2SeO3) and the effects of (S,S)
      ethylenediamine disuccinic acid (EDDS) thereon through X-ray diffraction (XRD),
      energy dispersive X-ray spectroscopy (EDXS) and Fourier transform infrared (FTIR)
      spectroscopy analyses. When EDDS concentrations were in the range of 0-1.0
      mmol/l, Se content increased significantly; however, at EDDS concentrations above
      this range, the symptoms of Se toxicity were alleviated in coleus leaves.
      Application of EDDS over 1.0 mmol/l significantly decreased total Se uptake in
      the leaves and roots of the plants. The powder diffraction patterns of the roots
      and leaves displayed sharp crystalline peaks, which were characteristic of an
      organic molecule with crystallinity. Our results revealed the presence of high
      amounts of C, O, Mg, Al, Si, K and Ca in the roots and leaves under Se-induced
      stress with different concentrations of EDDS. There were no changes in the
      chemical compositions of the roots and leaves, but the contents were influenced
      by Se-induced stress and EDDS treatment. This study demonstrated the importance
      of applying XRD, EDXS and FTIR methods toward a more comprehensive understanding
      of the mechanisms of EDDS-induced Se accumulation in plants. 

PMID- 25567190
TI  - Relationship between biomarkers and endocrine-disrupting compounds in wild
      Girardnichthys viviparus from two lakes with different degrees of pollution.
AB  - Despite great efforts worldwide to evaluate the effects of endocrine-disrupting
      compounds (EDCs) in fish, there is little information available about the
      interactions of EDCs with the disruption of the sexual endocrine axis in fish
      species with matrotrophic viviparity and intraluminal gestation. To understand
      these interactions, six sampling campaigns were performed within a period of 1
      year in two lakes with different degrees of pollution. A battery of biomarkers of
      the oestrogenic response was assessed in the liver [vitellogenin, CYP 1A1,
      epoxide hydrolase activity, and metallothioneins (MT)] and MT in the head of
      Girardinichthys viviparus. Linear correlation analysis and canonical
      correspondence analysis were performed to explore the relationship between the
      oestrogenic response with EDCs and with metals. The biomarker responses were
      assessed using the water content of EDCs (oestrone, 17-beta-oestradiol, oestriol,
      17-alpha-ethinyl oestradiol, total phenols, bisphenol A, nonyl phenol, octyl
      phenol), as well as the PAHs indene[1,2,3-c,d]pyrene, naphthalene, pyrene,
      benzo[a]anthracene, benzo[k]fluoranthene and benzo[a]pyrene) and metals (Cu, Fe,
      Mn, Pb and Zn). Greater disruption of the sexual endocrine axis occurred in fish
      of both sexes inhabiting the polluted lake whose effects were apparently
      influenced by CYP 1A1 activity and by 17-alpha-ethinyl oestradiol. In addition,
      non-estrogenic mechanisms in the hypothalamus and pituitary glands in male fish
      were observed, elicited by endogenous levels and the water concentration of Pb.
      In contrast, in females from the less polluted lake, VTG induction was related to
      exogenous oestrogens. The disruption of the hypothalamic-pituitary-gonadal axis
      is a complex process influenced by both endogenous and exogenous factors and
      contributes to male feminisation by exposure to EDCs. 

PMID- 25567194
TI  - High pressure induced spin state crossover in Sr2CaYCo4O10.5.
AB  - The layered cobaltite Sr(2)CaYCo(4)O(10.5) with formal average cobalt oxidation
      state close to 3+ has been studied as functions of both temperature and pressure
      up to 4 GPa by neutron powder diffraction (NPD). The crystal structure is shown
      to have tetragonal symmetry (space group I4/mmm; 2a(p) * 2a(p) * 4a(p)
      superstructure), and the magnetic structure at ambient pressure is found to be G
      type antiferromagnetic with TN close to 310 K. The magnetic moments within the
      CoO(6) octahedral layers and anion-deficient CoO(4.5) layers are 1.2MU(B) and
      2.8MU(B), respectively. At 25 K, and applied pressure of 3.5 GPa is sufficient to
      completely suppress a long-range magnetic order. This result is interpreted in
      terms of a pressure-induced high-to-low spin state crossover of the Co(3+) ions.

PMID- 25567193
TI  - The separation of Gln and Glu in STEAM: a comparison study using short and long
      TEs/TMs at 3 and 7 T.
AB  - OBJECTIVES: This study aimed to determine the optimal echo time (TE) and mixing
      time (TM) for in vivo glutamine (Gln) and glutamate (Glu) separation in
      stimulated-echo acquisition mode at 3 and 7 T. We applied a short TE/TM (20/10
      ms) for a high signal-to-noise-ratio and a field-specific long TE/TM (3 T: 72/6
      ms; 7 T: 74/68 ms) for optimal Gln and Glu separation of the Carbon-4 proton
      resonances. MATERIALS AND METHODS: Corresponding Gln and Glu spectra were
      simulated using VeSPA software, and measured in a phantom and human brains at 3
      and 7 T. RESULTS: Higher spectral separation for Gln and Glu was achieved at 7
      than 3 T. At 7 T, short TE/TM provided comparable spectral separation and in
      vitro Gln and Glu quantification compared to long TE/TM. Moreover, it showed
      greater reliability in in vivo Gln and Glu detection and separation than long
      TE/TM, with significantly lower Cramer-Rao lower bounds (Gln: 14.9 vs. 75.8; Glu:
      3.8 vs. 6.5) and correlation between Gln and Glu (p = 0.004). CONCLUSION: Based
      on the optimal separation for Gln and Glu, a short TE/TM at 7 T is proposed for
      future in vivo Gln and Glu acquisition.

PMID- 25567195
TI  - The application of atlantoaxial screw and rod fixation in revision operations for
      postoperative re-dislocation in children.
AB  - INTRODUCTION: We evaluate the feasibility, safety, and efficacy of atlantoaxial
      screw and rod fixation for revision operations in the treatment of re-dislocation
      after atlantoaxial operations in children. METHODS: Eight consecutive children
      with atlantoaxial instability required a revision operation due to atlantoaxial
      re-dislocation caused by the failure of the initial posterior wire fixation. The
      children were 5-11 years of age with an average age of 8.5 years. The posterior
      atlantoaxial screw and rod fixation and fusion operation was then performed.
      Autograft bones harvested from rib (in 3 patients), local bone (2 patients), and
      the iliac crest bone (3 patients) were used. RESULTS: There were no complications
      such as vertebral artery or spinal cord injury during the operations or loosening
      or fracture of the fixations after the operations. Stability and reduction of the
      atlantoaxial segments were achieved in all patients postoperatively. Follow-up
      time was 24-55 months, with an average of 35 months. All patients achieved solid
      osseous fusion demonstrated on plain radiographs or CT scanning. Atlantoaxial
      screw and rod fixation is feasible in children and may be considered for use
      during the initial operation in the treatment of atlantoaxial dislocation in
      children to minimize the need for a revision operation. CONCLUSION: If a revision
      operation is required, atlantoaxial screw-rod fixation is a safe and effective
      method. Because the anatomical structure is complicated in revision operation
      patients, CAD-RP technology could guide the the procedures of exposure and screw
      placement.

PMID- 25567196
TI  - Effects of low-doses of Bacillus spp. from permafrost on differentiation of bone
      marrow cells.
AB  - The effects of a new microorganism species (Bacillus spp., strain M3) isolated
      from permafrost specimens from Central Yakutia (Mamontova Mountain) on the bone
      marrow hemopoiesis were studied on laboratory mice. Analysis of the count and
      immunophenotype of bone marrow cells indicated that even in low doses (1000-5000
      microbial cells) these microorganisms modulated hemopoiesis and lymphopoiesis
      activity. The percentage of early hemopoietic precursors (CD117(+)CD34(-))
      increased, intensity of lymphocyte precursor proliferation and differentiation
      (CD25(+)CD44(-)) decreased, and the percentage of lymphocytes released from the
      bone marrow (CD25(+)CD44(+)) increased on day 21 after injection of the bacteria.
      These changes in activity of hemopoiesis were associated with changes in the
      level of regulatory T lymphocytes (reduced expression of TCRalphabeta) and were
      most likely compensatory. The possibility of modulating hemopoiesis activity in
      the bone marrow by low doses of one microorganism strain isolated from the
      permafrost could be useful for evaluating the effects of other low dose bacteria
      on the bone marrow hemopoiesis. 

PMID- 25567197
TI  - Immunohistochemical reactions of primary neuroendocrine breast cancer.
AB  - We performed immunohistochemical analysis of neuroendocrine breast cancer. The
      significance of this approach to differential diagnosis of this cancer form by
      detection of specific markers is demonstrated. The incidence of diagnosis of
      neuroendocrine breast cancer has increased 8-fold over 5 years. Neuroendocrine
      breast cancer is responsible for 3.4% of all breast cancer cases. The disease is
      significantly more incident in patients over 60. Neuroendocrine breast cancer is
      characterized by high expression of neuron-specific enolase (100%) and
      chromagranin A (57%). The data indicate that irrespective of the location,
      macroscopic picture, and immunohistochemical profile of cytokeratins and steroid
      hormones, breast cancer is characterized by clear-cut expression of
      neuroendocrine markers in different combinations. Immunohistochemical detection
      of these markers makes it possible to detect the hormone-secreting elements and
      evaluate their role in the tumor pool, which is essential for the differential
      diagnosis of neuroendocrine breast cancer, including studies of puncture biopsy
      specimens. 

PMID- 25567198
TI  - Simulation of category IIIB prostatitis.
AB  - Blood flow arrest in the inferior vena cava at the level of the inferior pole of
      the kidney led to the development of epithelial degeneration and stromal
      sclerosis after 1.5 months, dilatation of the veins, and congestion of secretion
      in rats. These signs corresponded to the morphological picture of category IIIB
      prostatitis or to signs of noninflammatory chronic prostatitis (hemodynamic
      disorders, sclerosis, degeneration). On the other hand, there was no cellular
      infiltration of the glandular tissue associated with infection and inflammation. 

PMID- 25567199
TI  - A new method for registration of kinesthetic evoked potentials for studies of
      proprioceptive sensitivity in normal subjects and patients with organic lesions
      in the brain.
AB  - The proprioceptive sensitivity of healthy volunteers and convalescents after
      acute cerebrovascular episodes was studied by a new neurophysiological method for
      registration of kinesthetic evoked potentials emerging in response to passive
      50(o) bending of the hand in the wrist joint with the angular acceleration of 350
      rad/sec(2). Kinesthetic evoked potentials were recorded above the somatosensory
      cortex projection areas in the hemispheres contra- and ipsilateral to the
      stimulated limb. The patients exhibited significantly longer latencies and lesser
      amplitudes of the early components of response in the involved hemisphere in
      comparison with normal subjects. The method for registration of the kinesthetic
      evoked potentials allows a more detailed study of the mechanisms of kinesthetic
      sensitivity in health and in organic involvement of the brain. 

PMID- 25567200
TI  - A new method for screening diagnosis of insulin resistance.
AB  - A simple method for the diagnosis of insulin resistance, easily realized in
      clinical practice, is developed in order to detect patients at a high risk of
      diseases associated with this condition. The metabolic index is estimated as the
      proportion of triglycerides and glucose values to quadratic HDL cholesterol value
      (in mmol/liter). The specific feature of this method for detection of insulin
      resistance in comparison with the known indirect methods is the use of routine
      biochemical values, evaluated in venous serum, for estimations. Estimation of
      this metabolic index is an economic and effective indirect method for evaluating
      the homeostasis system without additional evaluation of blood hormones.

PMID- 25567202
TI  - Metabolomic serum profiling detects early-stage high-grade serous ovarian cancer
      in a mouse model.
AB  - Ovarian cancer is a deadly disease killing more than any other gynecologic
      cancer. Nonspecific symptoms, combined with a lack of early detection methods,
      contribute to late diagnosis and low five-year survival rates. High-grade serous
      carcinoma (HGSC) is the most common and deadliest subtype that results in 90% of
      ovarian cancer deaths. To investigate metabolic patterns for early detection of
      this deadly ovarian cancer, Dicer-Pten double knockout (DKO) mice that phenocopy
      many of the features of metastatic HGSC observed in women were studied. Using
      ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), serum samples
      from 14 early-stage tumor (ET) DKO mice and 11 controls were analyzed in depth to
      screen for metabolic signatures capable of differentiating early-stage HGSC from
      controls. Iterative multivariate classification selected 18 metabolites that,
      when considered as a panel, yielded 100% accuracy, sensitivity, and specificity
      for classification. Altered metabolic pathways reflected in that panel included
      those of fatty acids, bile acids, glycerophospholipids, peptides, and some
      dietary phytochemicals. These alterations revealed impacts to cellular energy
      storage and membrane stability, as well as changes in defenses against oxidative
      stress, shedding new light on the metabolic alterations associated with early
      ovarian cancer stages. 

PMID- 25567204
TI  - Positron emission tomography-based evidence of low-amplitude respiratory motion
      in patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by low
      vital capacity and tidal volume, which translate into smaller respiratory
      motions. We sought to demonstrate the limited respiratory motion in COPD by
      comparing respiratory-gated and free-breathing positron emission tomography (PET)
      images of lung nodules ("CT-based" and "Ungated" images) in patients with and
      without COPD. METHODS: We studied 74 lung lesions (37 malignant) in 60 patients
      (23 patients with COPD; 37 without). An Ungated PET examination was followed by a
      CT-based acquisition. Maximum standard uptake value (SUVmax) for each lesion on
      PET images was measured. On CT images, we checked for the presence of emphysema
      and pleural adhesions or indentations associated with the nodules. Lastly, we
      used univariate and then multivariate analyses to determine the lung function
      parameters possibly affecting respiratory motion in patients with and without
      COPD. RESULTS: The mean "CT-based" vs. "Ungated" difference in SUVmax was 0.3 and
      0.6 for patients with and without COPD, respectively. Statistical analysis
      revealed that lesion site, hyperinflation and pleural indentation were
      independently associated with a difference in SUVmax. CONCLUSION: PET lung lesion
      images in patients with COPD are barely influenced by respiratory motion.
      Thoracic hyperinflation in patients with COPD was found to be independently
      associated with an effect of respiratory motion on PET images. Moreover, pleural
      indentation limits the respiratory motion of lung nodules, regardless of the
      presence or absence of COPD.

PMID- 25567201
TI  - Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disorder
      characterized by loss of motor neurons, resulting in paralysis and death.
      Multiple mechanisms of motor neuron injury have been implicated based upon the
      more than 20 different genetic causes of familial ALS. These inherited mutations
      compromise diverse motor neuron pathways leading to cell-autonomous injury. In
      the ALS transgenic mouse models, however, motor neurons do not die alone. Cell
      death is noncell-autonomous dependent upon a well orchestrated dialogue between
      motor neurons and surrounding glia and adaptive immune cells. The pathogenesis of
      ALS consists of 2 stages: an early neuroprotective stage and a later neurotoxic
      stage. During early phases of disease progression, the immune system is
      protective with glia and T cells, especially M2 macrophages/microglia, and T
      helper 2 cells and regulatory T cells, providing anti-inflammatory factors that
      sustain motor neuron viability. As the disease progresses and motor neuron injury
      accelerates, a second rapidly progressing phase develops, characterized by M1
      macrophages/microglia, and proinflammatory T cells. In rapidly progressing ALS
      patients, as in transgenic mice, neuroprotective regulatory T cells are
      significantly decreased and neurotoxicity predominates. Our own therapeutic
      efforts are focused on modulating these neuroinflammatory pathways. This review
      will focus on the cellular players involved in neuroinflammation in ALS and
      current therapeutic strategies to enhance neuroprotection and suppress
      neurotoxicity with the goal of arresting the progressive and devastating nature
      of ALS. 

PMID- 25567205
TI  - Complete genome sequence of nine isolates of canna yellow streak virus reveals
      its relationship to the sugarcane mosaic virus (SCMV) subgroup of potyviruses.
AB  - Complete genome sequences were obtained from nine isolates of canna yellow streak
      virus (CaYSV). CaYSV belongs to the sugarcane mosaic virus (SCMV) subgroup of
      potyviruses with johnsongrass mosaic virus (JGMV) as its closest relative.
      Multiple sequence alignments showed a pattern of amino acid substitutions in the
      CP sequences, which enabled us to relate these isolates to South East Asian or
      European isolates. Biological characterization of CaYSV identified Nicotiana
      benthamiana, Chenopodium quinoa and Phaseolus vulgaris as experimental hosts.
      Given the popularity and global trade of cannas, a clear picture of the genetic
      diversity of CaYSV is critical to disease management.

PMID- 25567203
TI  - Acquisition and loss of desiccation tolerance in seeds: from experimental model
      to biological relevance.
AB  - MAIN CONCLUSION: Besides being an important model to study desiccation tolerance,
      the induction of desiccation tolerance in germinated seeds may also play an
      ecological role in seedling establishment. Desiccation tolerance (DT) is the
      ability of certain organisms to survive extreme water losses without accumulation
      of lethal damage. This was a key feature in the conquering of dry land and is
      currently found in all taxa including bacteria, fungi, roundworms and plants. Not
      surprisingly, studies in various fields have been performed to unravel this
      intriguing phenomenon. In flowering plants, DT is rare in whole plants
      (vegetative tissues), yet is common in seeds. In this review, we present our
      current understanding of the evolution of DT in plants. We focus on the
      acquisition of DT in seeds and the subsequent loss during and after germination
      by highlighting and comparing research in two model plants Medicago truncatula
      and Arabidopsis thaliana. Finally, we discuss the ability of seeds to re
      establish DT during post-germination, the possible ecological meaning of this
      phenomenon, and the hypothesis that DT, in combination with dormancy, optimizes
      seedling establishment.

PMID- 25567206
TI  - More than a third of people with abnormal bowel cancer screening results avoid
      later screening.

PMID- 25567207
TI  - Increased expression of SOX4 is a biomarker for malignant status and poor
      prognosis in patients with non-small cell lung cancer.
AB  - The aim of the present study was to analyze the expression of sex-determining
      region Y-related high mobility group box 4 (SOX4) in non-small cell lung cancer
      (NSCLC) and its correlation with clinicopathologic characteristics, including the
      survival of NSCLC patients. To observe initially the expression status of SOX4 in
      lung squamous cell carcinoma and adenocarcinoma at gene expression omnibus. The
      expression of SOX4 mRNA and protein was examined in NSCLC tissues and normal lung
      tissues through real-time PCR and immunohistochemistry. Meanwhile, the
      relationship of SOX4 expression levels with clinical characteristics of 168 NSCLC
      patients was analyzed by immunohistochemistry. Univariate and multivariate
      analyses were performed to determine the association between SOX4 expression and
      prognosis of NSCLC patients. In our results, SOX4 expression was increased in
      NSCLC tissues compared with paired normal lung tissues in microarray data
      (GSE3268). SOX4 mRNA and protein expression were markedly higher in NSCLC tissues
      than in normal lung tissues (P = 0.001 and P = 0.001, respectively). Using
      immunohistochemistry, high levels of SOX4 protein were positively correlated with
      status of differentiated degree (high vs. middle, P = 0.004; high vs. low, P <
      0.001), clinical stage (I-II vs. III-IV, P < 0.001), T classification (T1-T2 vs.
      T3-T4, P = 0.004), N classification (N0-N1 vs. N2-N3, P = 0.002), and M
      classification (M0 vs. M1, P = 0.011) in NSCLC. Moreover, the higher level of
      SOX4 expression was markedly correlated with poor overall survival in NSCLC
      patients (P < 0.001). Multivariate analysis suggested that increased SOX4
      expression was a poor independent prognostic predictor for NSCLC patients (P =
      0.002). In conclusion, SOX4 plays an important role on NSCLC progression and
      prognosis and may serve as a convictive prognostic biomarker for NSCLC patients. 

PMID- 25567208
TI  - Anti-tumor properties of cis-resveratrol methylated analogs in metastatic mouse
      melanoma cells.
AB  - Resveratrol (E-3,5,4'-trihydroxystilbene) is a polyphenol found in red wine that
      has been shown to have multiple anti-cancer properties. Although cis-(Z)- and
      trans-(E)-isomers of resveratrol occur in nature, the cis form is not
      biologically active. However, methylation at key positions of the cis form
      results in more potent anti-cancer properties. This study determined that
      synthetic cis-polymethoxystilbenes (methylated analogs of cis-resveratrol)
      inhibited cancer-related phenotypes of metastatic B16 F10 and non-metastatic B16
      F1 mouse melanoma cells. In contrast with cis- or trans-resveratrol and trans
      polymethoxystilbene which were ineffective at 10 MUM, cis-polymethoxystilbenes
      inhibited motility and proliferation of melanoma cells with low micromolar
      specificity (IC50 < 10 MUM). Inhibitory effects by cis-polymethoxystilbenes were
      significantly stronger with B16 F10 cells and were accompanied by decreased
      expression of beta-tubulin and pleckstrin homology domain-interacting protein, a
      marker of metastatic B16 cells. Thus, cis-polymethoxystilbenes have potential as
      chemotherapeutic agents for metastatic melanoma. 

PMID- 25567210
TI  - Binary lanthanide(III)/nitrate and ternary lanthanide(III)/nitrate/chloride
      complexes in an ionic liquid containing water: optical absorption and
      luminescence studies.
AB  - The formation of binary Ln(iii)/nitrate and ternary Ln(iii)/nitrate/chloride
      complexes in a water-saturated ionic liquid, 1-butyl-3-methyl imidazolium
      bis(trifluoromethanesulfonyl)imide (denoted BumimTf(2)N), was investigated by
      absorption spectrophotometry and luminescence spectroscopy. Four successive
      binary complexes, Nd(NO(3))(2+), Nd(NO(3))(2)(+), Nd(NO(3))(3), and Nd(NO(3))(4)(
      ), were identified, and their stability constants in water-saturated BumimTf(2)N
      are several orders of magnitude higher than those in aqueous solutions, but much
      lower than those observed in dry BumimTf(2)N. The complexation of lanthanides
      with nitrate in wet BumimTf(2)N proceeds via the replacement of water molecules
      by bidentate nitrate anions from the inner solvation spheres of Ln(3+) cations.
      In the absence of nitrate, the precipitation of Ln(iii)/chloride complex(es)
      occurs at low ratios of C(Cl)/C(Ln) (<6) in BumimTf(2)N, which precludes the
      determination of stability constants of binary Ln(iii)/chloride complexes by
      spectrophotometry or luminescence spectroscopy. However, using a competition
      approach, the formation of two ternary complexes, Ln(NO(3))(3)Cl(2)(2-) and
      Ln(NO(3))(2)Cl(4)(3-), has been observed and their stability constants in wet
      BumimTf(2)N were determined. Data indicate that both nitrate and chloride are
      stronger ligands than water for lanthanides in BumimTf(2)N.

PMID- 25567209
TI  - Vascular regeneration effect of adipose-derived stem cells with light-emitting
      diode phototherapy in ischemic tissue.
AB  - The objective of this study was to investigate the effects on the vascular
      regeneration of adipose-derived stem cells (ASCs) by using red light-emitting
      diode (LED) irradiation in ischemic hind limbs. Low-level light therapy (LLLT)
      has been shown to enhance proliferation and cytokine secretion of a number of
      cells. ASCs are an attractive cell source for vascular tissue engineering. This
      approach is hindered because transplanted ASCs decline rapidly in the recipient
      tissue. Ischemic hind limbs were treated with LLLT from an LED array (660 nm) at
      an irradiance of 50 mW/cm(2) and a radiant exposure of 30 J/cm(2). LLLT, ASC
      transplantation, and ASC transplantation with LLLT (ASC + LLLT) were applied to
      ischemic limbs, and cell survival and differentiation, and secretion of vascular
      endothelial growth factor and basic fibroblast growth factor of the ASCs were
      evaluated by immunostaining and Western blot analyses. Vascular regeneration was
      assessed by immunostaining and hematoxylin and eosin staining. In the ASC + LLLT
      group, the survival of ASCs was increased due to the decreased apoptosis of ASCs.
      The secretion of growth factors was stimulated in this group compared with ASCs
      alone. The ASC + LLLT group displayed improved treatment efficacy including
      neovascularization and tissue regeneration compared with ASCs alone. In
      particular, quantitative analysis of laser Doppler blood perfusion image ratio
      showed that blood perfusion was enhanced significantly (p < 0.05) by ASC + LLLT
      treatment. These data suggest that LLLT is an effective biostimulator of ASCs in
      vascular regeneration, which enhances the survival of ASCs and stimulates the
      secretion of growth factors in ischemic limbs. 

PMID- 25567211
TI  - Screening for silent coronary artery disease in diabetics- or not?
AB  - The association between diabetes mellitus and coronary artery disease (CAD) is
      wellknown. Being the leading cause of death in diabetics, CAD is a target for
      prevention, diagnosis and treatment. In that sense, silent CAD in diabetics has
      long been a matter of concern, leading both to continued attempts at its
      diagnosis as well as to the persisting challenge of defining if screening for CAD
      in the diabetic population is useful and/or warranted. The most frequent and
      stronger point in favor of screening rests on the assumption that early diagnosis
      of CAD may lead to early treatment and therefore improved outcomes. Nonetheless,
      screening for CAD in diabetics is a controversial issue, since studies have not
      yielded evidence supporting better outcomes in diabetics screened for CAD
      compared to nonscreened diabetics. For several reasons, current tests that detect
      inducible ischemia or assess atherosclerotic burden may not be able to identify
      those patients at increased risk. Therefore a cautious look should be taken (once
      more) at that question. 

PMID- 25567212
TI  - Influenza vaccine effectiveness estimates in Croatia in 2010-2011: a season with
      predominant circulation of A(H1N1)pdm09 influenza virus.
AB  - This is a retrospective study using the test-negative case-control method to
      estimate seasonal 2010-2011 influenza vaccine effectiveness (VE) in Croatia. Of
      patients consulting a physician for influenza-like illness (ILI) and for whom a
      swab was taken, we compared RT-PCR influenza-positive and RT-PCR influenza
      negative patients. We used a structured questionnaire and physicians' records to
      obtain information on vaccination status and potential confounders. We conducted
      a complete case analysis using logistic regression to measure adjusted VE
      overall, against A(H1N1)pdm09 and in age groups. Out of 785 interviewed patients,
      495 eligible patients were included in the study, after applying exclusion
      criteria [217 cases, of which 92.6% were A(H1N1)pdm09 positive, 278 controls].
      Crude VE was 31.9% [95% confidence interval (CI) -40.9 to 67.1] and adjusted VE
      was 20.7% (95% CI -71.4 to 63.3), with higher VE in youngest and oldest age
      groups. Results from this first VE study in Croatia suggest a low to moderate VE
      for the 2010-2011 season. Studies year on year are needed with a greater sample
      size to provide more precise estimates, and also by age group and risk groups for
      vaccination. 

PMID- 25567213
TI  - The bitter pill.

PMID- 25567214
TI  - Pharmacokinetic effects of simultaneous administration of single-dose gabapentin
      500 mg and zolpidem tartrate 10 mg in healthy volunteers: a randomized, open
      label, crossover trial.
AB  - OBJECTIVE: Gabapentin is being investigated as a potential treatment for
      occasional disturbed sleep. This study assessed the pharmacokinetics and
      tolerability of gabapentin 500 mg and the commonly prescribed sedative/hypnotic
      zolpidem tartrate 10 mg, administered separately and in combination. METHODS:
      Forty healthy participants (19 male, 21 female) were randomized into this three
      period crossover study [mean (range) age 34.1 (18-45) years, weight 68.3 (51.4
      92.7) kg; 60 % white]. Participants were dosed with gabapentin alone (n = 39),
      zolpidem tartrate alone (n = 38), and the combination (gabapentin + zolpidem) (n
      = 38) over three treatment periods, which were separated by >=7 days. Blood
      samples were collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24
      and 36 h post-dose. Plasma concentrations of each drug were assayed using
      validated methods. Pharmacokinetic parameters were estimated from plasma
      concentration-time data using standard non-compartmental methods. RESULTS: For
      gabapentin + zolpidem combination versus gabapentin alone, mean pharmacokinetic
      parameters were peak plasma concentration (C max) 4.61 versus 4.72 ug/mL, time to
      Cmax (t max) 4.63 versus 3.64 h and the area under plasma concentration-time
      curve extrapolated to infinity (AUC0-infinity) 53.4 versus 51.0 ug h/mL. For the
      combination versus zolpidem alone, mean pharmacokinetic parameters were C max 154
      versus 138 ng/mL, t max 1.45 versus 1.84 h and AUC0-infinity 912 versus 854 ng
      h/mL. The 90 % confidence intervals for C max (rate of absorption) and AUC0
      infinity (extent of absorption) comparing the combination versus single drug
      administration fell within the 80-125 % range accepted for bioequivalence. All
      treatments were well tolerated. CONCLUSION: The pharmacokinetics of gabapentin
      500 mg and zolpidem tartrate 10 mg are unaffected when both drugs are taken
      simultaneously, compared with each drug taken alone.

PMID- 25567215
TI  - Gentamicin pharmacokinetics in critically ill patients during treatment with
      continuous venovenous haemodiafiltration (CVVHDF).

PMID- 25567216
TI  - Number of drugs in the medication list as an indicator of prescribing quality: a
      validation study of polypharmacy indicators in older hip fracture patients.
AB  - PURPOSE: Indicators based on the number of drugs in the medication list are
      sometimes used to reflect quality of drug treatment. This study aimed to evaluate
      the concurrent validity of such polypharmacy indicators, i.e., their ability to
      differentiate between appropriate and suboptimal drug treatment. METHODS: In 200
      hip fracture patients (>=65 years of age), consecutively recruited to a
      randomized controlled study in Sahlgrenska University Hospital in 2009, quality
      of drug treatment at study entry was assessed according to a gold standard as
      well as to indicators based on the number of drugs in the medication list. As
      gold standard, two specialist physicians independently assessed and then agreed
      on the quality for each patient, after initial screening with Screening Tool of
      Older Persons' potentially inappropriate Prescriptions (STOPP) and Screening Tool
      to Alert to Right Treatment (START). Suboptimal drug treatment was defined as >=1
      STOPP/START outcomes assessed as clinically relevant at the individual level.
      RESULTS: A total of 141 (71 %) patients had suboptimal drug treatment according
      to the gold standard. The corresponding figures according to the indicators >=5
      and >=10 drugs were 149 (75) and 49 (25 %), respectively. The sensitivity for the
      indicators >=5 and >=10 drugs to detect suboptimal drug treatment was 0.86 (95 %
      confidence interval: 0.80; 0.92) and 0.32 (0.25; 0.40), respectively. The
      specificity was 0.53 (0.41; 0.65) and 0.93 (0.82; 0.97). CONCLUSIONS: The
      findings suggest that no polypharmacy indicator could serve as a general
      indicator of prescribing quality; cut-offs for such indicators need to be chosen
      according to purpose.

PMID- 25567217
TI  - Association of ABCB1 polymorphisms with prognostic outcomes of anthracycline and
      cytarabine in Chinese patients with acute myeloid leukemia.
AB  - PURPOSE: To investigate the influence of ABCB1 polymorphisms on prognostic
      outcomes in Chinese patients with de novo intermediate-risk acute myeloid
      leukemia (AML) and to examine the gene expression level in relation to the
      genetic variation. METHODS: In total, 263 Chinese intermediate-risk AML patients
      treated with anthracycline and cytarabine were enrolled. G2677T, C1236T, and
      C3435T of the ABCB1 gene were analyzed by the allele-specific matrix-assisted
      laser desorption. Expression of ABCB1 messenger RNA (mRNA) was tested in 101
      patients of known genotype and haplotype for ABCB1 polymorphisms. Basic clinical
      characteristics of these patients were collected from medical records. RESULTS:
      Survival analysis showed that patients with AML (TTT haplotype) had a longer
      overall survival (OS) (p < 0.001, 29.2 months, 95 % confidence interval [CI],
      26.9-31.5 months) and relapse-free survival (RFS) (p = 0.005, 21.8 months, 95 %
      CI, 19.5-24.0 months) compared with those without TTT haplotype (21.9 months, 95
      % CI, 19.6-24.2 months; 16.5 months, 95 % CI, 14.6-18.5 months). After adjusting
      for age; gender; leukocyte count; hemoglobin level; platelet levels; French,
      American, and British classification; lactate dehydrogenase levels; Eastern
      Cooperative Oncology Group performance status; nucleophosmin gene; and fms
      related tyrosine kinase 3 gene, the multivariate survival analysis showed that
      the TTT haplotype appeared to be a predicting factor for OS (p = 0.001, hazard
      ratio = 1.854, 95 % CI, 1.301-2.641) and RFS (p = 0.009, hazard ratio = 1.755, 95
      % CI, 1.153-2.671). Moreover, a significant association between the TTT haplotype
      and relapse in AML patients was observed in this study (p = 0.002, odds ratio =
      0.410, 95 % CI, 0.235-0.715). Gene expression level was significantly lower in
      patients with the TTT haplotype than in the patients with the other haplotypes (p
      = 0.004). CONCLUSIONS: The findings suggested the TTT haplotype was possibly
      related to the OS, RFS, and relapse in Chinese patients with AML.

PMID- 25567218
TI  - Baclofen overdose treated with continuous venovenous hemofiltration.
AB  - PURPOSE: Overdose with baclofen, a derivative of the inhibitory neurotransmitter
      gamma-aminobutyric acid, may lead to severe respiratory and central nervous
      system depression and can be life-threatening. Prolonged half-lives of baclofen,
      of up to 34 h, have been reported in patients after overdose. Hemodialysis has
      proven to be a successful approach to improve clearance of baclofen, but the
      value of continuous venovenous hemofiltration (CVVH) is unclear. We applied CVVH
      in a patient with acute baclofen overdose. METHODS: Pharmacokinetic measurements
      of baclofen in serum and hemofiltrate were made at six time points after hospital
      admission. Baclofen concentration-time data were analyzed using non-compartmental
      methods, and the relative contribution of clearance by hemofiltration to total
      baclofen clearance was calculated. RESULTS: Baclofen concentrations in serum
      varied between 1.81 and 0.05 mg/L. Concentrations of baclofen in hemofiltrate
      were within the same range (between 0.74 and 0.05 mg/L), and the elimination half
      life during hemofiltration was estimated at 4.8 h. Total clearance and clearance
      via hemofiltration were estimated at 6.6 and 2.4 L/h, indicating that clearance
      could be increased by approximately 57 % by applying hemofiltration. CONCLUSIONS:
      The presented case demonstrates the usefulness of CVVH in the treatment of
      baclofen overdose and indicates that CVVH can be used as an alternative to
      hemodialysis in patients with overdose of baclofen.

PMID- 25567220
TI  - Laboratory diagnosis of bacterial gastroenteritis.
AB  - Bacterial gastroenteritis is a disease that is pervasive in both the developing
      and developed worlds. While for the most part bacterial gastroenteritis is self
      limiting, identification of an etiological agent by bacterial stool culture is
      required for the management of patients with severe or prolonged diarrhea,
      symptoms consistent with invasive disease, or a history that may predict a
      complicated course of disease. Importantly, characterization of bacterial
      enteropathogens from stool cultures in clinical laboratories is one of the
      primary means by which public health officials identify and track outbreaks of
      bacterial gastroenteritis. This article provides guidance for clinical
      microbiology laboratories that perform stool cultures. The general
      characteristics, epidemiology, and clinical manifestations of key bacterial
      enteropathogens are summarized. Information regarding optimal specimen
      collection, transport, and processing and current diagnostic tests and testing
      algorithms is provided. This article is an update of Cumitech 12A (P. H.
      Gilligan, J. M. Janda, M. A. Karmali, and J. M. Miller, Cumitech 12A, Laboratory
      diagnosis of bacterial diarrhea, 1992).

PMID- 25567223
TI  - Leprosy in the 21st century.
AB  - Despite significant improvements in leprosy (Hansen's disease) treatment and
      outlook for patients since the introduction of multidrug therapy (MDT) 3 decades
      ago, the global incidence remains high, and patients often have long-term
      complications associated with the disease. In this article, we discuss recent
      findings related to genetics, susceptibility, and disease reservoirs and the
      implications of these findings for Hansen's disease control and health outcomes
      for patients. We describe the continued difficulties associated with treatment of
      inflammatory episodes known as "leprosy reactions," which cause much of the
      disability associated with the disease and can affect people for many years after
      MDT is complete. We also discuss some of the contemporary challenges for
      physicians and patients, including international and internal migration of people
      affected by the disease. We suggest some important areas of focus for future
      Hansen's disease research.

PMID- 25567221
TI  - Comprehensive review of human sapoviruses.
AB  - Sapoviruses cause acute gastroenteritis in humans and animals. They belong to the
      genus Sapovirus within the family Caliciviridae. They infect and cause disease in
      humans of all ages, in both sporadic cases and outbreaks. The clinical symptoms
      of sapovirus gastroenteritis are indistinguishable from those caused by
      noroviruses, so laboratory diagnosis is essential to identify the pathogen.
      Sapoviruses are highly diverse genetically and antigenically. Currently, reverse
      transcription-PCR (RT-PCR) assays are widely used for sapovirus detection from
      clinical specimens due to their high sensitivity and broad reactivity as well as
      the lack of sensitive assays for antigen detection or cell culture systems for
      the detection of infectious viruses. Sapoviruses were first discovered in 1976 by
      electron microscopy in diarrheic samples of humans. To date, sapoviruses have
      also been detected from several animals: pigs, mink, dogs, sea lions, and bats.
      In this review, we focus on genomic and antigenic features, molecular
      typing/classification, detection methods, and clinical and epidemiological
      profiles of human sapoviruses.

PMID- 25567222
TI  - Kingella kingae: carriage, transmission, and disease.
AB  - Kingella kingae is a common etiology of pediatric bacteremia and the leading
      agent of osteomyelitis and septic arthritis in children aged 6 to 36 months. This
      Gram-negative bacterium is carried asymptomatically in the oropharynx and
      disseminates by close interpersonal contact. The colonized epithelium is the
      source of bloodstream invasion and dissemination to distant sites, and certain
      clones show significant association with bacteremia, osteoarthritis, or
      endocarditis. Kingella kingae produces an RTX (repeat-in-toxin) toxin with broad
      spectrum cytotoxicity that probably facilitates mucosal colonization and
      persistence of the organism in the bloodstream and deep body tissues. With the
      exception of patients with endocardial involvement, children with K. kingae
      diseases often show only mild symptoms and signs, necessitating clinical acumen.
      The isolation of K. kingae on routine solid media is suboptimal, and detection of
      the bacterium is significantly improved by inoculating exudates into blood
      culture bottles and the use of PCR-based assays. The organism is generally
      susceptible to antibiotics that are administered to young patients with joint and
      bone infections. beta-Lactamase production is clonal, and the local prevalence of
      beta-lactamase-producing strains is variable. If adequately and promptly treated,
      invasive K. kingae infections with no endocardial involvement usually run a
      benign clinical course.

PMID- 25567227
TI  - Antimicrobial heteroresistance: an emerging field in need of clarity.
AB  - "Heteroresistance" describes a phenomenon where subpopulations of seemingly
      isogenic bacteria exhibit a range of susceptibilities to a particular antibiotic.
      Unfortunately, a lack of standard methods to determine heteroresistance has led
      to inappropriate use of this term. Heteroresistance has been recognized since at
      least 1947 and occurs in Gram-positive and Gram-negative bacteria. Its clinical
      relevance may be considerable, since more resistant subpopulations may be
      selected during antimicrobial therapy. However, the use of nonstandard methods to
      define heteroresistance, which are costly and involve considerable labor and
      resources, precludes evaluating the clinical magnitude and severity of this
      phenomenon. We review the available literature on antibiotic heteroresistance and
      propose recommendations for definitions and determination criteria for
      heteroresistant bacteria. This will help in assessing the global clinical impact
      of heteroresistance and developing uniform guidelines for improved therapeutic
      outcomes.

PMID- 25567226
TI  - Avian schistosomes and outbreaks of cercarial dermatitis.
AB  - Cercarial dermatitis (swimmer's itch) is a condition caused by infective larvae
      (cercariae) of a species-rich group of mammalian and avian schistosomes. Over the
      last decade, it has been reported in areas that previously had few or no cases of
      dermatitis and is thus considered an emerging disease. It is obvious that avian
      schistosomes are responsible for the majority of reported dermatitis outbreaks
      around the world, and thus they are the primary focus of this review. Although
      they infect humans, they do not mature and usually die in the skin. Experimental
      infections of avian schistosomes in mice show that in previously exposed hosts,
      there is a strong skin immune reaction that kills the schistosome. However,
      penetration of larvae into naive mice can result in temporary migration from the
      skin. This is of particular interest because the worms are able to migrate to
      different organs, for example, the lungs in the case of visceral schistosomes and
      the central nervous system in the case of nasal schistosomes. The risk of such
      migration and accompanying disorders needs to be clarified for humans and animals
      of interest (e.g., dogs). Herein we compiled the most comprehensive review of the
      diversity, immunology, and epidemiology of avian schistosomes causing cercarial
      dermatitis.

PMID- 25567231
TI  - Prolonged clinical remissions in patients with relapsed or refractory follicular
      lymphoma treated with autologous stem cell transplantation incorporating
      rituximab.
AB  - Three sequential phase II trials were conducted with different immunotherapy
      approaches to enhance the outcome of autologous transplant (high-dose therapy and
      autologous stem cell transplantation (HDT/ASCT)) for recurrent follicular
      lymphoma. Seventy-three patients were enrolled from 1996 to 2009. Patients
      received HDT/ASCT combined with (1) interferon-alpha 3 MU/m(2) subcutaneously
      (SC) three times per week (TIW) for 2 years post-ASCT, (2) rituximab (R) 375
      mg/m(2) for in vivo purging 3-5 days pre-stem cell collection and 2 * 4 weekly R
      at 2 and 6 months post-ASCT, respectively, or (3) three infusions of R pre-stem
      cell collection followed by 6* R weekly and interferon-alpha 3 MU/m(2) SC TIW.
      Although not statistically significant, progression-free survival (PFS) for
      patients who received rituximab was 56.4 and 49.1% at 5 and 10 years compared to
      36 and 21% in those who did not receive rituximab. Molecular relapse post
      HDT/ASCT was the strongest predictor of PFS in a multivariate analysis. Molecular
      relapse was coincident with or preceded clinical relapses in 84% of patients who
      relapsed-median of 12 months (range 0-129 months). Adverse events included
      secondary malignancy, transformation to diffuse large B cell lymphoma, prolonged
      mostly asymptomatic hypogammaglobulinemia, and pulmonary fibrosis. The long-term
      toxicity profile must be considered when selecting patients for this treatment.

PMID- 25567232
TI  - Synthesis of a novel water-soluble cylindrical macrotricyclic host and its
      complexation with N-methylquinolinium and N-methylisoquinolinium salts: formation
      of 1 : 2 complexes in water.
AB  - A novel water-soluble cylindrical macrotricyclic host containing one central
      cavity and two dibenzo-24-crown-8 lateral cavities was synthesized. It could form
      1 : 2 complexes with N-methylquinolinium salts or N-methylisoquinolinium salts in
      water solution and in the solid state, in which multiple hydrogen-bonding and pi
      pi stacking interactions between the host and the guests played an important
      role. Moreover, the complexation and decomplexation of the complexes between the
      host and the guests could be achieved by changing the pH of the solution, and the
      process could also be observed by the naked eye. 

PMID- 25567234
TI  - The anion exchange strategy towards mesoporous alpha-Ni(OH)2 nanowires with
      multinanocavities for high-performance supercapacitors.
AB  - By exploiting a facile and controllable anion exchange strategy, mesoporous alpha
      Ni(OH)2 nanowires with multinanocavities in surfaces have been successfully
      developed. The novel nanoscale morphology has been proven to be responsible for
      their excellent capacitive performances. 

PMID- 25567233
TI  - Landscape ethnoecological knowledge base and management of ecosystem services in
      a Szekely-Hungarian pre-capitalistic village system (Transylvania, Romania).
AB  - BACKGROUND: Previous studies showed an in-depth ecological understanding by
      traditional people of managing natural resources. We studied the landscape
      ethnoecological knowledge (LEEK) of Szekelys on the basis of 16-19(th) century
      village laws. We analyzed the habitat types, ecosystem services and sustainable
      management types on which village laws had focused. METHODS: Szekelys had self
      governed communities formed mostly of "noble peasants". Land-use was dominated by
      commons and regulated by village laws framed by the whole community. Seventy-two
      archival laws from 52 villages, resulting in 898 regulations, were analyzed using
      the DPSIR framework. Explicit and implicit information about the contemporary
      ecological knowledge of Szekelys was extracted. We distinguished between
      responses that limited use and supported regeneration and those that protected
      produced/available ecosystem services and ensured their fair distribution.
      RESULTS: Most regulations referred to forests (674), arable lands (562), meadows
      (448) and pastures (134). Szekelys regulated the proportion of arable land,
      pasture and forest areas consciously in order to maximize long-term exploitation
      of ecosystem services. The inner territory was protected against overuse by
      relocating certain uses to the outer territory. Competition for ecosystem
      services was demonstrated by conflicts of pressure-related (mostly personal) and
      response-related (mostly communal) driving forces. Felling of trees (oaks),
      grazing of forests, meadows and fallows, masting, use of wild apple/pear trees
      and fishing were strictly regulated. Cutting of leaf-fodder, grazing of green
      crops, burning of forest litter and the polluting of streams were prohibited.
      Marketing by villagers and inviting outsiders to use the ecosystem services were
      strictly regulated, and mostly prohibited. Szekelys recognized at least 71 folk
      habitat types, understood ecological regeneration and degradation processes, the
      history of their landscape and the management possibilities of ecosystem
      services. Some aspects of LEEK were so well known within Szekely communities that
      they were not made explicit in village laws, others remained implicit because
      they were not related to regulations. CONCLUSIONS: Based on explicit and implicit
      information, we argue that Szekelys possessed detailed knowledge of the local
      ecological system. Moreover the world's first known explicit mention of ecosystem
      services ("Benefits that are provided by Nature for free") originated from this
      region from 1786.

PMID- 25567235
TI  - Making assessment locally relevant: measuring functioning for maternal depression
      in Khayelitsha, Cape Town.
AB  - PURPOSE: We developed a locally relevant functioning assessment instrument (FAI)
      for pregnant women and mothers of young babies to complement a widely validated
      instrument-the World Health Organization's Disability Assessment Schedule
      (WHODAS) 12-item version. The FAI is an outcome measure in a randomised
      controlled trial on the effectiveness of a lay counsellor administered
      intervention for distressed pregnant women in Khayelitsha, Cape Town. METHODS:
      Nine items most commonly reported by 40 pregnant women or mothers with young
      babies in qualitative interviews were selected for the instrument, with a 10th
      item 'Other'. The FAI was validated with 142 pregnant women and mothers in
      Khayelitsha. Analysis was conducted to assess internal reliability, exploratory
      factor analysis and convergent validity. RESULTS: The FAI had good internal
      reliability (Cronbach's alpha = 0.77) and the explanatory factor analysis showed
      a clear 3-factor solution, relating to domestic, childcare and social activities.
      The FAI scores showed floor effects, but were positively correlated with the two
      measures of functioning (WHODAS 2.0 and Washington Group Short Set). The FAI
      scores also correlated with the measure of depression (Edinburgh Postnatal
      Depression Scale-EPDS), reflecting increased functional limitations associated
      with increased depressive symptoms. CONCLUSION: The results show that the FAI has
      good internal reliability, and good convergent and construct validity as a
      measure of functioning for this context. This paper reports on the process of
      developing an instrument and highlights the importance of using instruments that
      are locally relevant to ensure accurate measurement of functional status.

PMID- 25567236
TI  - Geography, Race/Ethnicity, and Obesity Among Men in the United States.
AB  - The prevalence of obesity in the United States has increased significantly and is
      a particular concern for minority men. Studies focused at the community and
      national levels have reported that geography can play a substantial role in
      contributing to obesity, but little is known about how regional influences
      contribute to obesity among men. The objective of this study is to examine the
      association between geographic region and obesity among men in the United States
      and to determine if there are racial/ethnic differences in obesity within these
      geographic regions. Data from men, aged 18 years and older, from the National
      Health Interview Survey were combined for the years 2000 to 2010. Obesity was
      defined as body mass index (BMI) >=30 kg/m(2) Logistic regression models were
      specified to calculate the odds ratio (OR) and 95% confidence interval (CI) for
      the association between geographic region and obesity and for race and obesity
      within geographic regions. Compared to men living in the Northeast, men living in
      the Midwest had significantly greater odds of being obese (OR = 1.09, 95% CI
      [1.02, 1.17]), and men living in the West had lower odds of being obese (OR =
      0.82, 95% CI [0.76, 0.89]). Racial/ethnic differences were also observed within
      geographic region. Black men have greater odds of obesity than White men in the
      South, West, and Midwest. In the South and West, Hispanic men also have greater
      odds of obesity than White men. In all regions, Asian men have lower odds of
      obesity than White men.

PMID- 25567237
TI  - Lagged effects of early-season herbivores on valley oak fecundity.
AB  - The seasonal match between folivore and leaf phenology affects the annual success
      of arboreal folivore populations because many folivores exploit developing
      leaves, which are an ephemeral resource. One strategy for folivores to exploit
      early-season leaves is to anticipate their emergence. The consequence of this
      behavior for trees is that individuals that set leaves earlier may experience
      greater rates of folivore damage, with potential negative fitness consequences.
      To test this hypothesis, we surveyed the early-season phenology, insect folivore
      damage, and acorn crop of a population of valley oaks (Quercus lobata) over a 3
      year period. We found that trees that set leaves earlier experienced greater
      rates of folivore damage than trees that set leaves later in the season. In
      addition, we observed a lagged effect of folivore damage on acorn production,
      whereby trees with greater leaf damage produced fewer acorns in the subsequent
      year. These results indicate potential negative fitness consequences of earlier
      leaf phenology. Our study suggests that folivore pressure may be one factor that
      affects the optimal timing of leaf set in oaks. 

PMID- 25567238
TI  - A study on the inhibition of dihydrofolate reductase (DHFR) from Escherichia coli
      by gold(i) phosphane compounds. X-ray crystal structures of (4,5-dichloro-1H
      imidazolate-1-yl)-triphenylphosphane-gold(i) and (4,5-dicyano-1H-imidazolate-1
      yl)-triphenylphosphane-gold(i).
AB  - An unprecedented study on the inhibitory activities of a class of phosphane
      gold(i) complexes on E. coli dihydrofolate reductase (DHFR) is reported. The
      gold(i) complexes considered in this work consist of azolate or chloride ligands
      and phosphane as co-ligands. The ligands have been functionalized with polar
      groups (-COOH, -COO(-), NO2, Cl, CN) to obtain better solubility in polar media.
      Neutral, anionic and cationic gold(i) complexes have been tested as DHFR
      inhibitors by means of a continuous direct spectrophotometric method. X-ray
      structural characterizations were performed on ((triphenylphosphine)-gold(i)-(4,5
      dicyanoimidazolyl-1H-1yl) and on the analog (triphenylphosphine)-gold(i)-(4,5
      dichloroimidazolyl-1H-1yl). The inhibition constants obtained from the enzyme
      tests range from 20 MUM to 63 nM (auranofin) and are conducive to promoting these
      compounds as potential DHFR inhibitors. 

PMID- 25567239
TI  - Water-assisted production of honeycomb-like g-C3N4 with ultralong carrier
      lifetime and outstanding photocatalytic activity.
AB  - Graphitic carbon nitride (g-C3N4) is a visible light photocatalyst, limited by
      low activity mainly caused by rapid recombination of charge carriers. In the
      present work, honeycomb-like g-C3N4 was synthesized via thermal condensation of
      urea with addition of water at 450  degrees C for 1 h. Prolonging the
      condensation time caused the morphology of g-C3N4 to change from a porous
      honeycomb structure to a velvet-like nanoarchitecture. Unlike in previous
      studies, the photocatalytic activity of g-C3N4 decreased with increasing surface
      area. The honeycomb-like g-C3N4 with a relatively low surface area showed highly
      enhanced photocatalytic activity with an NO removal ratio of 48%. The evolution
      of NO2 intermediate was dramatically inhibited over the honeycomb-like g-C3N4.
      The short and long lifetimes of the charge carriers for honeycomb-like g-C3N4
      were unprecedentedly prolonged to 22.3 and 165.4 ns, respectively. As a result,
      the honeycomb-like g-C3N4 was highly efficient and stable in activity and could
      be used repeatedly. Addition of water had the following multiple positive effects
      on g-C3N4: (1) formation of the honeycomb structure, (2) promotion of charge
      separation and migration, (3) enlargement of the band gap, (4) increase in
      production yield, and (5) decrease in energy cost. These advantages make the
      present preparation method for highly efficient g-C3N4 extremely appealing for
      large-scale applications. The active species produced from g-C3N4 under
      illumination were confirmed using DMPO-ESR spin-trapping, the reaction
      intermediate was monitored, and the reaction mechanism of photocatalytic NO
      oxidation by g-C3N4 was revealed. This work could provide an attractive
      alternative method for mass-production of highly active g-C3N4-based
      photocatalysts for environmental and energetic applications. 

PMID- 25567229
TI  - The rebirth of culture in microbiology through the example of culturomics to
      study human gut microbiota.
AB  - Bacterial culture was the first method used to describe the human microbiota, but
      this method is considered outdated by many researchers. Metagenomics studies have
      since been applied to clinical microbiology; however, a "dark matter" of
      prokaryotes, which corresponds to a hole in our knowledge and includes minority
      bacterial populations, is not elucidated by these studies. By replicating the
      natural environment, environmental microbiologists were the first to reduce the
      "great plate count anomaly," which corresponds to the difference between
      microscopic and culture counts. The revolution in bacterial identification also
      allowed rapid progress. 16S rRNA bacterial identification allowed the accurate
      identification of new species. Mass spectrometry allowed the high-throughput
      identification of rare species and the detection of new species. By using these
      methods and by increasing the number of culture conditions, culturomics allowed
      the extension of the known human gut repertoire to levels equivalent to those of
      pyrosequencing. Finally, taxonogenomics strategies became an emerging method for
      describing new species, associating the genome sequence of the bacteria
      systematically. We provide a comprehensive review on these topics, demonstrating
      that both empirical and hypothesis-driven approaches will enable a rapid increase
      in the identification of the human prokaryote repertoire.

PMID- 25567240
TI  - Gating of responsive multiple nanochannels by ultra-low concentration of
      saccharides.
AB  - We report a saccharide recognition system by modifying responsive copolymers on
      the solid-based multiple nanochannels. The ion transport through nanochannels can
      be regulated by ultra-low concentration of saccharides, which can switch
      nanochannels between the "on" and "off" states. 

PMID- 25567228
TI  - Current and past strategies for bacterial culture in clinical microbiology.
AB  - A pure bacterial culture remains essential for the study of its virulence, its
      antibiotic susceptibility, and its genome sequence in order to facilitate the
      understanding and treatment of caused diseases. The first culture conditions
      empirically varied incubation time, nutrients, atmosphere, and temperature;
      culture was then gradually abandoned in favor of molecular methods. The rebirth
      of culture in clinical microbiology was prompted by microbiologists specializing
      in intracellular bacteria. The shell vial procedure allowed the culture of new
      species of Rickettsia. The design of axenic media for growing fastidious bacteria
      such as Tropheryma whipplei and Coxiella burnetii and the ability of amoebal
      coculture to discover new bacteria constituted major advances. Strong efforts
      associating optimized culture media, detection methods, and a microaerophilic
      atmosphere allowed a dramatic decrease of the time of Mycobacterium tuberculosis
      culture. The use of a new versatile medium allowed an extension of the repertoire
      of archaea. Finally, to optimize the culture of anaerobes in routine bacteriology
      laboratories, the addition of antioxidants in culture media under an aerobic
      atmosphere allowed the growth of strictly anaerobic species. Nevertheless, among
      usual bacterial pathogens, the development of axenic media for the culture of
      Treponema pallidum or Mycobacterium leprae remains an important challenge that
      the patience and innovations of cultivators will enable them to overcome.

PMID- 25567225
TI  - Norovirus.
AB  - Norovirus, an RNA virus of the family Caliciviridae, is a human enteric pathogen
      that causes substantial morbidity across both health care and community settings.
      Several factors enhance the transmissibility of norovirus, including the small
      inoculum required to produce infection (<100 viral particles), prolonged viral
      shedding, and its ability to survive in the environment. In this review, we
      describe the basic virology and immunology of noroviruses, the clinical disease
      resulting from infection and its diagnosis and management, as well as host and
      pathogen factors that complicate vaccine development. Additionally, we discuss
      overall epidemiology, infection control strategies, and global reporting efforts
      aimed at controlling this worldwide cause of acute gastroenteritis. Prompt
      implementation of infection control measures remains the mainstay of norovirus
      outbreak management.

PMID- 25567241
TI  - "Paradoxical" EEG response to propofol may differentiate post-cardiac arrest non
      convulsive status epilepticus from diffuse irreversible cerebral anoxia.
AB  - Current EEG criteria for the diagnosis of non-convulsive status epilepticus in
      critically ill patients with repetitive generalised or focal epileptiform
      discharges primarily rely on a widely accepted low cut-off frequency limit of 2.5
      3 Hz for non-evolving patterns, or on discharge evolution of frequency, location
      or mophology. The secondary criterion is a significant clinical or EEG
      improvement following acute administration of a rapidly acting antiepileptic
      drug, such as lorazepam. We describe a comatose patient after out-of-hospital
      cardiac arrest, in whom very slow (1-Hz), non-evolving generalised periodic
      epileptiform discharges against an almost completely depressed background would
      suggest substantial anoxic damage and poor neurological outcome. Yet, reloading
      with propofol for diagnostic purposes completely dispersed generalised periodic
      epileptiform discharges and revealed previously absent biological activity,
      raising the possibility of non-convulsive status epilepticus that was
      subsequently confirmed. Brain MRI showed no significant anoxic brain damage and
      EEG improved, but the patient died from severe cardiopulmonary complications.
      These observations suggest that in rare cases, slow, non-evolving generalised
      periodic epileptiform discharges may reflect non-convulsive status epilepticus
      rather than diffuse irreversible cerebral anoxia, while reloading with propofol
      can be used as an additional secondary diagnostic criterion. 

PMID- 25567243
TI  - The role of iron in the preparation and oxygen reduction reaction activity of
      nitrogen-doped carbon.
AB  - It has been considered that the presence of Fe-N in the carbon network helps to
      enhance oxygen reduction reaction (ORR) activity of the carbon. In this study, N
      doped platelet ordered mesoporous carbon is prepared using Fe-phthalocyanine as a
      single precursor for nitrogen, iron and carbon sources. We show that the physical
      presence of Fe is not necessary to enhance the ORR activity of N-doped carbon,
      although Fe is required to create more active sites and to increase the
      electrical conductivity in the carbon framework. 

PMID- 25567244
TI  - A new tool for predicting drought: an application over India.
AB  - This is the first attempt of application of atmospheric electricity for rainfall
      prediction. The atmospheric electrical columnar resistance based on the model
      calculations involving satellite data has been proposed as a new predictor. It is
      physically sound, simple to calculate and not probabilistic like the standardized
      precipitation index. After applying this new predictor over India, it has been
      found that the data solely over the Bay of Bengal (BB) are sufficient to predict
      a drought over the country as a whole. Finally, two independent new methods to
      predict drought conditions and a preliminary forecast of the same for India for
      year 2014 have been given. Unlike the existing drought prediction techniques, the
      identification of drought conditions in a pre-drought year during 1981-1990 and
      2001-2013 over India has been achieved 100% successfully using the suggested new
      methods. The association between rainfall and this new predictor has also been
      found on the sub-regional scale. So, the present predictor is expected to get
      global application and application in climate models. From the analysis,
      generally, a long period rising trend in aerosol concentration over the BB causes
      weak monsoon over India but that for a short time i.e. in pre-monsoon period
      strengthens it. 

PMID- 25567242
TI  - Pregnancy serum concentrations of perfluorinated alkyl substances and offspring
      behaviour and motor development at age 5-9 years--a prospective study.
AB  - BACKGROUND: In animal studies, perfluorinated alkyl substances affect growth and
      neuro-behavioural outcomes. Human epidemiological studies are sparse. The aim was
      to investigate the association between pregnancy serum concentrations of
      perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and offspring
      behaviour and motor development at 5-9 years of age. METHODS: Maternal sera from
      the INUENDO cohort (2002-2004) comprising 1,106 mother-child pairs from
      Greenland, Kharkiv (Ukraine) and Warsaw (Poland) were analysed for PFOS and PFOA,
      using liquid-chromatography-tandem-mass-spectrometry. Exposures were grouped into
      country specific as well as pooled tertiles as well as being used as continuous
      variables for statistical analyses. Child motor development and behaviour at
      follow-up (2010-2012) were measured by the Developmental Coordination Disorder
      Questionnaire 2007 (DCDQ) and Strength and Difficulties Questionnaire (SDQ),
      respectively. Exposure-outcome associations were analysed by multiple logistic
      and linear regression analyses. RESULTS: In the pooled analysis, odds ratio (OR)
      (95% confidence interval (CI)) for hyperactivity was 3.1 (1.3, 7.2) comparing
      children prenatally exposed to the highest PFOA tertile with those exposed to the
      lowest PFOA tertile. Comparing children in the highest PFOS tertile with those in
      the lowest PFOS tertile showed elevated but statistically non-significant OR of
      hyperactivity (OR (95% CI) 1.7 (0.9, 3.2)). In Greenland, elevated PFOS was
      associated with higher SDQ-total scores indicating more behavioural problems
      (beta (95% CI)=1.0 (0.1, 2.0)) and elevated PFOA was associated with higher
      hyperactivity sub-scale scores indicating more hyperactive behaviour (beta (95%
      CI)=0.5 (0.1, 0.9)). Prenatal PFOS and PFOA exposures were not associated with
      motor difficulties. CONCLUSIONS: Prenatal exposure to PFOS and PFOA may have a
      small to moderate effect on children's neuro-behavioural development,
      specifically in terms of hyperactive behaviour. The associations were strongest
      in Greenland where exposure contrast is largest.

PMID- 25567246
TI  - Reasons to be cheerful.

PMID- 25567245
TI  - Listen up.

PMID- 25567247
TI  - Economic divide taking toll on European science.

PMID- 25567259
TI  - Greek science haunted by hydra of problems.

PMID- 25567224
TI  - Current and emerging Legionella diagnostics for laboratory and outbreak
      investigations.
AB  - Legionnaires' disease (LD) is an often severe and potentially fatal form of
      bacterial pneumonia caused by an extensive list of Legionella species. These
      ubiquitous freshwater and soil inhabitants cause human respiratory disease when
      amplified in man-made water or cooling systems and their aerosols expose a
      susceptible population. Treatment of sporadic cases and rapid control of LD
      outbreaks benefit from swift diagnosis in concert with discriminatory bacterial
      typing for immediate epidemiological responses. Traditional culture and serology
      were instrumental in describing disease incidence early in its history;
      currently, diagnosis of LD relies almost solely on the urinary antigen test,
      which captures only the dominant species and serogroup, Legionella pneumophila
      serogroup 1 (Lp1). This has created a diagnostic "blind spot" for LD caused by
      non-Lp1 strains. This review focuses on historic, current, and emerging
      technologies that hold promise for increasing LD diagnostic efficiency and
      detection rates as part of a coherent testing regimen. The importance of
      cooperation between epidemiologists and laboratorians for a rapid outbreak
      response is also illustrated in field investigations conducted by the CDC with
      state and local authorities. Finally, challenges facing health care
      professionals, building managers, and the public health community in combating LD
      are highlighted, and potential solutions are discussed.

PMID- 25567260
TI  - End of cancer-genome project prompts rethink.

PMID- 25567261
TI  - Korea opens up its ocean science.

PMID- 25567262
TI  - Rave drug tested against depression.

PMID- 25567264
TI  - Military health: The insurmountable gulf.

PMID- 25567265
TI  - Environmental science: Pollution patrol.

PMID- 25567266
TI  - Immunology: Fifty years of B lymphocytes.

PMID- 25567271
TI  - Pollution: Uncouple from economy boom.

PMID- 25567273
TI  - Pollution: Clear blue skies over Beijing.

PMID- 25567272
TI  - Global vision: International Council for Science responds.

PMID- 25567274
TI  - Publishing costs: Peer review as a business transaction.

PMID- 25567275
TI  - Pollution: Build on success in China.

PMID- 25567276
TI  - Climate science: Unburnable fossil-fuel reserves.

PMID- 25567278
TI  - Quantum information: Spin memories in for the long haul.

PMID- 25567279
TI  - Regenerative biology: The versatile and plastic liver.

PMID- 25567282
TI  - The temperature and chronology of heavy-element synthesis in low-mass stars.
AB  - Roughly half of the heavy elements (atomic mass greater than that of iron) are
      believed to be synthesized in the late evolutionary stages of stars with masses
      between 0.8 and 8 solar masses. Deep inside the star, nuclei (mainly iron)
      capture neutrons and progressively build up (through the slow-neutron-capture
      process, or s-process) heavier elements that are subsequently brought to the
      stellar surface by convection. Two neutron sources, activated at distinct
      temperatures, have been proposed: (13)C and (22)Ne, each releasing one neutron
      per alpha-particle ((4)He) captured. To explain the measured stellar abundances,
      stellar evolution models invoking the (13)C neutron source (which operates at
      temperatures of about one hundred million kelvin) are favoured. Isotopic ratios
      in primitive meteorites, however, reflecting nucleosynthesis in the previous
      generations of stars that contributed material to the Solar System, point to
      higher temperatures (more than three hundred million kelvin), requiring at least
      a late activation of (22)Ne (ref. 1). Here we report a determination of the s
      process temperature directly in evolved low-mass giant stars, using zirconium and
      niobium abundances, independently of stellar evolution models. The derived
      temperature supports (13)C as the s-process neutron source. The radioactive pair
      (93)Zr-(93)Nb used to estimate the s-process temperature also provides, together
      with the pair (99)Tc-(99)Ru, chronometric information on the time elapsed since
      the start of the s-process, which we determine to be one million to three million
      years. 

PMID- 25567283
TI  - Optically addressable nuclear spins in a solid with a six-hour coherence time.
AB  - Space-like separation of entangled quantum states is a central concept in
      fundamental investigations of quantum mechanics and in quantum communication
      applications. Optical approaches are ubiquitous in the distribution of
      entanglement because entangled photons are easy to generate and transmit.
      However, extending this direct distribution beyond a range of a few hundred
      kilometres to a worldwide network is prohibited by losses associated with
      scattering, diffraction and absorption during transmission. A proposal to
      overcome this range limitation is the quantum repeater protocol, which involves
      the distribution of entangled pairs of optical modes among many quantum memories
      stationed along the transmission channel. To be effective, the memories must
      store the quantum information encoded on the optical modes for times that are
      long compared to the direct optical transmission time of the channel. Here we
      measure a decoherence rate of 8 * 10(-5) per second over 100 milliseconds, which
      is the time required for light transmission on a global scale. The measurements
      were performed on a ground-state hyperfine transition of europium ion dopants in
      yttrium orthosilicate ((151)Eu(3+):Y2SiO5) using optically detected nuclear
      magnetic resonance techniques. The observed decoherence rate is at least an order
      of magnitude lower than that of any other system suitable for an optical quantum
      memory. Furthermore, by employing dynamic decoupling, a coherence time of 370 +/-
      60 minutes was achieved at 2 kelvin. It has been almost universally assumed that
      light is the best long-distance carrier for quantum information. However, the
      coherence time observed here is long enough that nuclear spins travelling at 9
      kilometres per hour in a crystal would have a lower decoherence with distance
      than light in an optical fibre. This enables some very early approaches to
      entanglement distribution to be revisited, in particular those in which the spins
      are transported rather than the light. 

PMID- 25567281
TI  - Glutathione activates virulence gene expression of an intracellular pathogen.
AB  - Intracellular pathogens are responsible for much of the world-wide morbidity and
      mortality due to infectious diseases. To colonize their hosts successfully,
      pathogens must sense their environment and regulate virulence gene expression
      appropriately. Accordingly, on entry into mammalian cells, the facultative
      intracellular bacterial pathogen Listeria monocytogenes remodels its
      transcriptional program by activating the master virulence regulator PrfA. Here
      we show that bacterial and host-derived glutathione are required to activate
      PrfA. In this study a genetic selection led to the identification of a bacterial
      mutant in glutathione synthase that exhibited reduced virulence gene expression
      and was attenuated 150-fold in mice. Genome sequencing of suppressor mutants that
      arose spontaneously in vivo revealed a single nucleotide change in prfA that
      locks the protein in the active conformation (PrfA*) and completely bypassed the
      requirement for glutathione during infection. Biochemical and genetic studies
      support a model in which glutathione-dependent PrfA activation is mediated by
      allosteric binding of glutathione to PrfA. Whereas glutathione and other low
      molecular-weight thiols have important roles in redox homeostasis in all forms of
      life, here we demonstrate that glutathione represents a critical signalling
      molecule that activates the virulence of an intracellular pathogen. 

PMID- 25567280
TI  - Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism.
AB  - Yeasts, which have been a component of the human diet for at least 7,000 years,
      possess an elaborate cell wall alpha-mannan. The influence of yeast mannan on the
      ecology of the human microbiota is unknown. Here we show that yeast alpha-mannan
      is a viable food source for the Gram-negative bacterium Bacteroides
      thetaiotaomicron, a dominant member of the microbiota. Detailed biochemical
      analysis and targeted gene disruption studies support a model whereby limited
      cleavage of alpha-mannan on the surface generates large oligosaccharides that are
      subsequently depolymerized to mannose by the action of periplasmic enzymes. Co
      culturing studies showed that metabolism of yeast mannan by B. thetaiotaomicron
      presents a 'selfish' model for the catabolism of this difficult to breakdown
      polysaccharide. Genomic comparison with B. thetaiotaomicron in conjunction with
      cell culture studies show that a cohort of highly successful members of the
      microbiota has evolved to consume sterically-restricted yeast glycans, an
      adaptation that may reflect the incorporation of eukaryotic microorganisms into
      the human diet. 

PMID- 25567284
TI  - High-value alcohols and higher-oxidation-state compounds by catalytic Z-selective
      cross-metathesis.
AB  - Olefin metathesis catalysts provide access to molecules that are indispensable to
      physicians and researchers in the life sciences. A persisting problem, however,
      is the dearth of chemical transformations that directly generate acyclic Z
      allylic alcohols, including products that contain a hindered neighbouring
      substituent or reactive functional units such as a phenol, an aldehyde, or a
      carboxylic acid. Here we present an electronically modified ruthenium-disulfide
      catalyst that is effective in generating such high-value compounds by cross
      metathesis. The ruthenium complex is prepared from a commercially available
      precursor and an easily generated air-stable zinc catechothiolate.
      Transformations typically proceed with 5.0 mole per cent of the complex and an
      inexpensive reaction partner in 4-8 hours under ambient conditions; products are
      obtained in up to 80 per cent yield and 98:2 Z:E diastereoselectivity. The use of
      this catalyst is demonstrated in the synthesis of the naturally occurring anti
      tumour agent neopeltolide and in a single-step stereoselective gram-scale
      conversion of a renewable feedstock (oleic acid) to an anti-fungal agent. In this
      conversion, the new catalyst promotes cross-metathesis more efficiently than the
      commonly used dichloro-ruthenium complexes, indicating that its utility may
      extend beyond Z-selective processes. 

PMID- 25567285
TI  - The geographical distribution of fossil fuels unused when limiting global warming
      to 2  degrees C.
AB  - Policy makers have generally agreed that the average global temperature rise
      caused by greenhouse gas emissions should not exceed 2  degrees C above the
      average global temperature of pre-industrial times. It has been estimated that to
      have at least a 50 per cent chance of keeping warming below 2  degrees C
      throughout the twenty-first century, the cumulative carbon emissions between 2011
      and 2050 need to be limited to around 1,100 gigatonnes of carbon dioxide (Gt
      CO2). However, the greenhouse gas emissions contained in present estimates of
      global fossil fuel reserves are around three times higher than this, and so the
      unabated use of all current fossil fuel reserves is incompatible with a warming
      limit of 2  degrees C. Here we use a single integrated assessment model that
      contains estimates of the quantities, locations and nature of the world's oil,
      gas and coal reserves and resources, and which is shown to be consistent with a
      wide variety of modelling approaches with different assumptions, to explore the
      implications of this emissions limit for fossil fuel production in different
      regions. Our results suggest that, globally, a third of oil reserves, half of gas
      reserves and over 80 per cent of current coal reserves should remain unused from
      2010 to 2050 in order to meet the target of 2  degrees C. We show that
      development of resources in the Arctic and any increase in unconventional oil
      production are incommensurate with efforts to limit average global warming to 2 
      degrees C. Our results show that policy makers' instincts to exploit rapidly and
      completely their territorial fossil fuels are, in aggregate, inconsistent with
      their commitments to this temperature limit. Implementation of this policy
      commitment would also render unnecessary continued substantial expenditure on
      fossil fuel exploration, because any new discoveries could not lead to increased
      aggregate production. 

PMID- 25567286
TI  - EFF-1-mediated regenerative axonal fusion requires components of the apoptotic
      pathway.
AB  - Functional regeneration after nervous system injury requires transected axons to
      reconnect with their original target tissue. Axonal fusion, a spontaneous
      regenerative mechanism identified in several species, provides an efficient means
      of achieving target reconnection as a regrowing axon is able to contact and fuse
      with its own separated axon fragment, thereby re-establishing the original axonal
      tract. Here we report a molecular characterization of this process in
      Caenorhabditis elegans, revealing dynamic changes in the subcellular localization
      of the EFF-1 fusogen after axotomy, and establishing phosphatidylserine (PS) and
      the PS receptor (PSR-1) as critical components for axonal fusion. PSR-1 functions
      cell-autonomously in the regrowing neuron and, instead of acting in its canonical
      signalling pathway, acts in a parallel phagocytic pathway that includes the
      transthyretin protein TTR-52, as well as CED-7, NRF-5 and CED-6 (refs 9, 10, 11,
      12). We show that TTR-52 binds to PS exposed on the injured axon, and can restore
      fusion several hours after injury. We propose that PS functions as a 'save-me'
      signal for the distal fragment, allowing conserved apoptotic cell clearance
      molecules to function in re-establishing axonal integrity during regeneration of
      the nervous system. 

PMID- 25567288
TI  - Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal
      aberrations in the zygote by maternal misrepair.
AB  - De novo point mutations and chromosomal structural aberrations (CSA) detected in
      offspring of unaffected parents show a preferential paternal origin with higher
      risk for older fathers. Studies in rodents suggest that heritable mutations
      transmitted from the father can arise from either paternal or maternal misrepair
      of damaged paternal DNA, and that the entire spermatogenic cycle can be at risk
      after mutagenic exposure. Understanding the susceptibility and mechanisms of
      transmission of paternal mutations is important in family planning after
      chemotherapy and donor selection for assisted reproduction. We report that
      treatment of male mice with melphalan (MLP), a bifunctional alkylating agent
      widely used in chemotherapy, induces DNA lesions during male mouse meiosis that
      persist unrepaired as germ cells progress through DNA repair-competent phases of
      spermatogenic development. After fertilization, unrepaired sperm DNA lesions are
      mis-repaired into CSA by the egg's DNA repair machinery producing chromosomally
      abnormal offspring. These findings highlight the importance of both pre- and post
      fertilization DNA repair in assuring the genomic integrity of the conceptus. 

PMID- 25567289
TI  - Economic evaluation of the practical approach to lung health and informal
      provider interventions for improving the detection of tuberculosis and chronic
      airways disease at primary care level in Malawi: study protocol for cost
      effectiveness analysis.
AB  - BACKGROUND: Chronic airway diseases pose a big challenge to health systems in
      most developing countries, particularly in Sub-Saharan Africa. A diagnosis for
      people with chronic or persistent cough is usually delayed because of individual
      and health system barriers. However, delayed diagnosis and treatment facilitates
      further transmission, severity of disease with complications and mortality. The
      objective of this study is to assess the cost-effectiveness of the practical
      approach to lung health strategy, a patient-centred approach for diagnosis and
      treatment of common respiratory illnesses in primary healthcare settings, as a
      means of strengthening health systems to improve the quality of management of
      respiratory diseases. METHODS/DESIGN: Economic evaluation nested in a cluster
      randomised controlled trial with three arms will be performed. Measures of
      effectiveness and costs for all arms of the study will be obtained from the
      cluster randomised controlled clinical trial. The main outcome measures are a
      combined rate of major respiratory diseases milestones and process indicators
      extracted from the practical approach to lung health strategy. For analysis,
      descriptive as well as regression techniques will be used. A cost-effectiveness
      analysis will be performed according to intention-to-treat principle and from a
      societal perspective. Cost-effectiveness ratios will be calculated using
      bootstrapping techniques. DISCUSSION: We hope to demonstrate the cost
      effectiveness of the practical approach to lung health and informal healthcare
      providers, see an improvement in patients' quality of life, achieve a reduction
      in the duration and occurrence of episodes and the chronicity of respiratory
      diseases, and are able to report a decrease in the social cost. If the practical
      approach to lung health and informal healthcare provider's interventions are cost
      effective, they could be scaled up to all primary healthcare centres. TRIAL
      REGISTRATION: PACTR: PACTR201411000910192.

PMID- 25567290
TI  - Quantitative assessment of Abeta peptide in brain, cerebrospinal fluid and plasma
      following oral administration of gamma-secretase inhibitor MRK-560 in rats.
AB  - The beta-amyloid peptides (Abeta) are thought to play a critical role in the
      pathophysiology of Alzheimer's disease. One therapeutic strategy aimed to reduce
      or eliminate the production of Abeta peptides is inhibition of the gamma
      secretase enzyme, which cleaves amyloid precursor protein to form Abeta peptides.
      We studied the in vivo effects of the potent, orally bioavailable and brain
      penetrant gamma-secretase inhibitor (GSI), MRK-560, on both Abetax-40 and Abetax
      42 in multiple compartments (plasma, the brain and cerebrospinal fluid) of rat.
      Although there were differences in the time course and magnitude of the changes,
      the results showed that MRK-560 caused marked inhibition of both Abetax-40 and
      Abetax-42 in all three compartments. We identified good correlations between
      plasma Abetax-40 versus brain Abetax-40 (r = 0.84), and plasma Abetax-40 versus
      CSF Abetax-40 (r = 0.85), indicating that these pools of Abeta are related
      dynamically. These results suggest that central Abeta changes that occur
      following acute dosing with MRK-560 can be predicted based on plasma Abeta
      changes and could thus serve as a useful biomarker to help accelerate decision
      making during early clinical development. 

PMID- 25567292
TI  - Prevalence of canid herpesvirus-1 infection in stillborn and dead neonatal
      puppies in Denmark.
AB  - BACKGROUND: Canid herpesvirus-1 (CaHV-1) infection in puppies less than three
      weeks of age is often reported to be associated with a lethal generalized
      necrotizing inflammation and since the discovery of the virus in 1965 several
      reports of neonatal infections have been published. However, the significance of
      CaHV-1 for peri- and neonatal mortality in puppies remains unclear. Therefore, we
      examined stillborn and dead neonatal puppies in Denmark to determine the
      prevalence of infection and further to correlate infection levels with necropsy
      findings to assess the possible significance of the infection. RESULTS: From a
      cross-sectional study of 57 dead puppies, 22.8% (n = 13) were confirmed positive
      for CaHV-1 by real-time polymerase chain reaction (PCR) of tissue pools of
      lung/liver and/or spleen/kidney. Specimens from PCR positive cases were further
      investigated by histology and in situ hybridization (ISH). High levels of CaHV-1
      DNA were present in only one case in which lesions and ISH staining consistent
      with CaHV-1 infection were found as well. CaHV-1 concentrations in the other
      cases were low and a range of lesions not consistent with CaHV-1 were found.
      Similar, ISH staining was mostly negative in these except for one case with a few
      positive cells. CONCLUSION: CaHV-1 infection in stillborn and dead neonatal
      puppies in Denmark seems to be common, but the direct significance for puppy
      mortality remains unclear as only one of 13 PCR positive puppies (7.7%) had
      pathognomonic lesions.

PMID- 25567293
TI  - Study on Artificial Food Colors in Beverages Is Inaccurate.

PMID- 25567291
TI  - Multi-Drug Resistance ABC Transporter Inhibition Enhances Murine Ventral Prostate
      Stem/Progenitor Cell Differentiation.
AB  - Multi-drug resistance (MDR)-ATP binding cassette (ABC) transporters, ABCB1,
      ABCC1, and ABCG2 participate in the efflux of steroid hormones, estrogens, and
      androgens, which regulate prostate development and differentiation. The role of
      MDR-ABC efflux transporters in prostate epithelial proliferation and
      differentiation remains unclear. We hypothesized that MDR-ABC transporters
      regulate prostate differentiation and epithelium regeneration. Prostate
      epithelial differentiation was studied using histology, sphere formation assay,
      and prostate regeneration induced by cycles of repeated androgen withdrawal and
      replacement. Embryonic deletion of Abcg2 resulted in a decreased number of
      luminal cells in the prostate and increased sphere formation efficiency,
      indicating an imbalance in the prostate epithelial differentiation pattern.
      Decreased luminal cell number in the Abcg2 null prostate implies reduced
      differentiation. Enhanced sphere formation efficiency in Abcg2 null prostate
      cells implies activation of the stem/progenitor cells. Prostate regeneration was
      associated with profound activation of the stem/progenitor cells, indicating the
      role of Abcg2 in maintaining stem/progenitor cell pool. Since embryonic deletion
      of Abcg2 may result in compensation by other ABC transporters, pharmacological
      inhibition of MDR-ABC efflux was performed. Pharmacological inhibition of MDR-ABC
      efflux enhanced prostate epithelial differentiation in sphere culture and during
      prostate regeneration. In conclusion, Abcg2 deletion leads to activation of the
      stem/progenitor cells and enhances differentiating divisions; and pharmacological
      inhibition of MDR-ABC efflux leads to epithelial differentiation. Our study
      demonstrates for the first time that MDR-ABC efflux transporter inhibition
      results in enhanced prostate epithelial cell differentiation. 

PMID- 25567295
TI  - The full spectrum of hepatic steatosis in children.
AB  - OBJECTIVE: We aim to identify the spectrum of etiologies of steatosis in
      pediatric liver biopsies. METHODS: Information was collected from 155 children
      with steatosis on liver biopsy, including anthropometrics, laboratory, and
      radiologic data. Biopsies were reviewed by a liver pathologist. RESULTS: The 4
      major diagnoses associated with hepatic steatosis were nonalcoholic fatty liver
      disease (37%), metabolic disease (9%), oncologic disease (8%) and viral hepatitis
      (7%). Patients with nonalcoholic fatty liver disease were older (P = .0001) and
      more likely to have a body mass index z score >2 (P < .0001). Patients with a
      metabolic diagnosis were younger (P = .0002). Radiologic imaging of the liver
      yielded normal results in 44 of 108 of children (30%); 7 of these had >66%
      macrovesicular fatty change on biopsy, and 3 had severe fibrosis/cirrhosis.
      CONCLUSIONS: The range of causes of steatosis in pediatric liver biopsies is
      broad. Not all patients, even with advanced liver disease, had abnormalities with
      liver imaging, emphasizing the role for liver biopsy in certain cases.

PMID- 25567294
TI  - Caregiver Preferences Regarding Personal Health Records in the Management of
      ADHD.
AB  - OBJECTIVE: Personal health records (PHRs) may address the needs of children with
      attention deficit hyperactivity disorder. Among parents, we assessed acceptance,
      barriers, and intentions regarding use of PHR for their children with attention
      deficit hyperactivity disorder. METHODS: Survey of parents from 3 practices in
      Rochester, NY. Stepwise logistic regression analysis explored factors predicting
      respondents' intentions for future use of PHR, accounting for care coordination
      needs, caregiver education, socioeconomic status, and satisfaction with
      providers. RESULTS: Of 184 respondents, 23% had used the PHR for their child, 82%
      intended future use. No difference was observed between users and nonusers
      regarding gender, age, race, or education. Users were more likely than nonusers
      to reside in the suburbs (P = .03). Caregivers were more likely to plan future
      use of the PHR if they felt engaged as partners in their child's care (adjusted
      odds ratio = 2.3, 95% confidence interval = 1.2, 4.5). CONCLUSIONS: Parents are
      enthusiastic about PHRs. Future work should focus on engaging them as members of
      the health care team.

PMID- 25567297
TI  - Anti-inflammatory and immunomodulatory effects of Spirulina platensis in
      comparison to Dunaliella salina in acetic acid-induced rat experimental colitis.
AB  - CONTEXT: Spirulina platensis (SP) is used as a source of protein and vitamin
      supplement in humans without any significant side-effects. Dunaliella salina (DS)
      is also regarded as one of the richest natural producers of carotenoid, thus used
      as a source of antioxidants to protect cells from oxidative damage. OBJECTIVE:
      The aim of the present study is to compare the ameliorative effect of Spirulina
      and Dunaliella in experimental colitis. MATERIALS AND METHODS: Spirulina and
      Dunaliella were investigated at the same dose of 500 mg/kg body weight for their
      modulatory effect against acetic-acid induced ulcerative colitis (UC) in rats.
      The colonic lesion was analyzed by examining macroscopic damage, bloody diarrhea
      scores, colon weight/length and change in body weight of tested rats. Colon lipid
      peroxidation and oxidative stress markers were examined by evaluating
      malondialdehyde (MDA), protein carbonyl (PCO), catalase (CAT), reduced
      glutathione (GSH) and superoxide dismutase (SOD). Colon inflammatory markers;
      myeloperoxidase (MPO) and prostaglandin (PGE2) as well as proinflammatory
      cytokines; tumor necrosis factor (TNF-alpha) and interleukins (IL-1beta, IL-6)
      were also studied. RESULTS: The colonic mucosal injury, biochemical and
      histopathologic results suggest that both SP and DS exhibit significant
      modulatory effect on acetic acid-induced colitis in rats, which may be due to a
      significant increase of antioxidant enzymes activity and significant inhibition
      of lipid peroxidation and inflammation markers. DISCUSSION: Results showed that
      in comparison to Sulfasalazine, SP exhibited better therapeutic and safety
      profile than DS against acetic acid-induced UC. CONCLUSION: This study suggests
      potential benefits of SP and DS in an experimental model of colitis.

PMID- 25567296
TI  - Evaluation and Treatment of Severe Obesity in Childhood.

PMID- 25567298
TI  - Pharmacokinetics of enrofloxacin and marbofloxacin in Japanese quails and common
      pheasants.
AB  - The pharmacokinetics of enrofloxacin and marbofloxacin was studied in Japanese
      quails and common pheasants. Healthy mature birds from both species and both
      genders were treated intravenously and orally with enrofloxacin (10 mg/kg) and
      marbofloxacin (5 mg/kg). After intravenous administration enrofloxacin was
      extensively metabolised to ciprofloxacin. Metabolites of marbofloxacin were not
      detected. Values of volume of distribution were respectively 4.63 l/kg and 3.67
      l/kg for enrofloxacin and 1.56 l/kg and 1.43 l/kg for marbofloxacin. In quails,
      total body clearance values were higher than those in pheasants and other avian
      species. After oral application enrofloxacin was rapidly absorbed in quails, more
      rapidly than marbofloxacin. Pheasants absorbed both antimicrobials at a lower
      rate. Higher bioavailability was observed for marbofloxacin (118%). Relatively
      low bioavailability was established in quails for enrofloxacin (26.4%),
      accompanied by extensive conversion to ciprofloxacin. Generally, quails absorbed
      and eliminated both fluoroquinolones more rapidly than pheasants; the latter
      showed pharmacokinetics similar to poultry. Because of favourable pharmacokinetic
      properties, marbofloxacin should be preferred for oral administration in Japanese
      quails and pheasants for treatment of infections caused by equally susceptible
      pathogens. 

PMID- 25567299
TI  - The effect of electromagnetic fields on biofouling in a heat exchange system
      using seawater.
AB  - This article discusses the antifouling action of a continuous physical treatment
      process comprising the application of electromagnetic fields (EMFs) to seawater
      used as the refrigerant fluid in a heat exchanger-condenser to maintain the
      initial 'clean tube' condition. The results demonstrated that the EMFs
      accelerated the ionic nucleation of calcium and precipitation as calcium
      carbonate, which weakened the growing biofilm and reduced its adhesion capacity.
      Consequently, EMFs induced an erosive effect that reduced biofilm formation and
      fouling. This treatment allowed for the maintenance of significantly lower
      fouling factors in the treated tubes compared to a control group of untreated
      tubes, thereby leading to a higher heat transfer efficiency. 

PMID- 25567300
TI  - [Application and advances of diffusion-weighted imaging in diagnosis and
      treatment of breast cancer].

PMID- 25567301
TI  - [A comparative analysis of the changes of transcriptome after fusion of
      esophageal cancer cells with human umbilical mesenchymal stem cells].
AB  - OBJECTIVE: To compare the transcriptome of esophageal cancer cells (EC9706),
      human mesenchymal stem cells (MSCs), and after fusion of esophageal cancer cells
      with MSCs, and to further study their different expression profiles and the
      changes of their signaling pathways. METHODS: We examined the gene expression
      profiles of these cells with transcriptome microarray using LIMMA package and
      several web-based applications, such as DAVID, ToppGene and MSigDB. The resulting
      sets of differentially expressed genes (DEGs) were comprehensively analyzed to
      identify the pathways and their changes after the cell fusion. RESULTS: A total
      of 4 548 significantly DEGs among the three cell lines were found by LIMMA. Three
      functional annotation web tools predicted that DNA damage repair, cell cycle
      arrest and apoptosis pathways were enriched. Total DEGs were mapped to the
      canonic pathways with KEGGanim which depicted that the core genes of DNA damage
      repair, cell cycle arrest and pro-apoptosis were up-regulated in fusion cells,
      and they mightbe combined to respond the fusion-induced damage stress. The up
      regulation of suppressive factor DUSP6 might feedback inhibit the MAPK signaling
      pathway in the fusion cells, too. CONCLUSIONS: Transcriptome analysis suggests
      that hMSCs and EC9706 cell fusion may inhibit growth of EC cells by induction of
      pro-apoptotic signaling and DUSP6 negative feedback inhibition mechanism. In
      addition, the changes of immune regulation-related and differentiation-related
      genes indicate that the fusion cells inherited certain immune-suppressive
      function from the stem cells.

PMID- 25567302
TI  - [Influence of interference of WIG-1 on the multi-drug resistance in small cell
      lung cancer].
AB  - OBJECTIVE: To investigate the role of wild-type p53-induced gene 1 (WIG-1) on the
      regulation of multi-drug resistance in small cell lung cancer. METHODS: The
      expressions of WIG-1 protein and gene were detected by Western blot and real-time
      PCR (RT-PCR) in both the drug-sensitive H69 and drug-resistant H69AR cell lines,
      respectively. Meanwhile, the differential expression of WIG-1 was also detected
      in peripheral blood samples of responders and non-responder patients.
      Furthermore, the WIG-1 expression was inhibited by siRNA in H69AR cells, then the
      drug-sensitivities of H69AR cells to chemotherapy agents such as ADM, DDP, VP-16
      were detected by CCK8 assay, and apoptosis rate was detected by flow cytometry.
      The possible association of WIG-1 with clinical parameters was evaluated.
      RESULTS: The expression of WIG-1 was significantly increased in H69AR cells
      (5.965 +/- 0.890) than that in the H69 cells (1.023 +/- 0.127) (P = 0.007). The
      expression of WIG-1 was significantly increased in the non-responder patients
      (4.169 +/- 0. 970) than in the H69 cells and responders (1.673 +/- 0.127) (P <
      0.001). The drug-sensitivities of H69AR cells to chemotherapeutic drugs were
      increased when the expression of the WIG-1 was down-regulated. The apoptosis rate
      was significantly decreased in the H69AR cells (1.037 +/- 0.049)% compared with
      that in the H69 cells [(7.963 +/- 0.097)%, (P < 0.01)]. The apoptosis rate was
      increased in the H69AR-Si-WIG-1 cells (20.915 +/- 0.890)% than that of (1.037 +/-
      0.049)% in the H69AR and H69AR-NC group (2.025 +/- 0.097)% (P < 0.01). The
      expression of WIG-1 was not significantly associated with gender, and age (P >
      0.05), but significantly correlated with chemosensitivity, overall survival and
      clinical stage (P < 0.001 for all). CONCLUSIONS: Our results suggest that WIG-1
      is involved in the regulation of the multidrug resistance mechanism in small cell
      lung cancer. Selective silencing of the WIG-1 gene may reverse the multidrug
      resistance of SCLC via increasing cell apoptosis.

PMID- 25567303
TI  - [microRNA-140 suppresses the migration and invasion of colorectal cancer cells
      through targeting Smad3].
AB  - OBJECTIVE: To investigate the effect of microRNA-140 (miR-140) on the migration
      and invasion of colorectal cancer (CRC) cells and the possible mechanism.
      METHODS: miR-140 mimics, miR-140 specific inhibitor or small interfering RNA
      (siRNA) against Smad3 were transfected into human CRC cell line RKO cells
      respectively, using Oligofectamine or Lipofectamine2000. Quantitative real-time
      PCR (real-time PCR) was used to measure the expression levels of miR-140 and
      Smad3 mRNA. Smad3 protein was analyzed by Western blot. The in vitro cell
      migrating and invasive abilities were determined by wound-healing and Transwell
      chamber assay after up-regulating or down-regulating miR-140 or knocking down
      Smad3. RESULTS: The Western blot assays showed that the Smad3 protein level was
      significantly reduced after up-regulating miR-140 (0.04 +/- 0.01), compared with
      that of (0.47 +/- 0.02, P < 0.05) in the control group and that of (0.52 +/-
      0.06) in the negative control group (P < 0.05 for both). The results of real-time
      PCR indicated that no significant difference was found in the levels of Smad3
      mRNA between miR-140 transfection and NC groups (1.11 +/- 0.13 vs. 1.00 +/- 0.06,
      P > 0.05). The wound-healing assay showed that the migrating ability was
      dramatically attenuated by miR-140 compared with that in the control and NC
      groups, whereas no significance was found when compared with that of the Smad3
      siRNA transfected cells. The number of cells migrating through Transwell chamber
      without matrigel in the miR-140 group was (76.2 +/- 4.4), remarkably lowered than
      that in the control (267.1 +/- 4.9) and NC (336.1 +/- 5.7) groups (P < 0.05 for
      both), but no significant difference between the miR-140 (76.2 +/- 4.4) and Smad3
      siRNA (83.5 +/- 7.3) groups. Transwell chamber with matrigel assay showed that
      number of cells penetrating through the membrane was (109.5 +/- 7.4) in the miR
      140 group, significantly lower than that in the control (403.1 +/- 5.1) and NC
      (392.6 +/- 8.4) groups (P < 0.05 for both), while Smad3 siRNA transfection had a
      similar effect (138.8 +/- 3.6)(P > 0.05). Down-regulation of miR-140 increased
      the level of smad3 protein expression, and partially reversed the inhibition of
      the cell migration and invasion mediated by miR-140. Co-transfection of miR-140
      inhibitor and Smad3 siRNA had no significant effect on the Smad3 protein
      expression and the abilities of cell migration and invasion. CONCLUSIONS: miR-140
      regulates the Smad3 expression at the post-transcriptional level. miR-140
      suppresses the migrating and invasive abilities of CRC cells, possibly through
      down-regulation of Smad3. The findings of this study suggest that miR-140 may
      have a unique potential as a possible biomarker candidate for diagnosis and
      therapy of tumor metastasis.

PMID- 25567304
TI  - [Therapeutic study of leukemia by pegylated liposomal daunorubicin].
AB  - OBJECTIVE: To explore the antitumor effect and toxicity of pegylated liposomal
      daunorubicin (PL-DNR) on leukemia. METHODS: PL-DNR was prepared by dry lipid
      hydration and remote loading, and its physicochemical indexes were analyzed. The
      inhibiting effect of PL-DNR on leukemia cells was observed in terms of in vitro
      cytotoxicity experiment. The therapeutic effect in vivo was assessed by tumor
      inhibition in leukemia L1210-bearing mice. Apoptosis in cardiomyocytes was
      detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end
      labeling method (TUNEL staining). RESULTS: The average diameter of PL-DNR was
      (110 +/- 10)nm and the encapsulation efficiency was 94.21%. The in vitro
      cytotoxicity experiment showed that the inhibiting ability of PL-DNR in the
      treatment groups was continuously enhanced as the experiment proceeded. The in
      vivo pharmacodynamic experiment also indicated obvious tumor-inhibiting effect of
      PL-DNR. At the end of the experiment, the tumor volume of the PL-DNR group was
      (433.71 +/- 234.77)mm(3), significantly smaller than that of (1 293.77 +/-
      381.26) mm(3) in the DNR group (P < 0.05). Moreover, the tumor weight of the PL
      DNR group was (0.66 +/- 0.29)g and that of the DNR group was (1.25 +/- 0.43)g (P
      < 0.05). The myocardial toxicity experiment showed that the median apoptosis
      index of cardiomyocytes in the PL-DNR group was 13.83%, significantly lower than
      that of 42.67% in the DNR group (P < 0.05), indicating a lower toxicity of PL-DNR
      to the myocardium. CONCLUSION: Compared with the free DNR, PL-DNR can improve the
      therapeutic effect on leukemia and reduce the.

PMID- 25567305
TI  - [Detection of ROS1 gene rearrangement by FISH and analysis of its clinical
      features in non-small cell lung cancer patients].
AB  - OBJECTIVE: To detect the frequency of ROS1 gene rearrangement in non-small cell
      lung cancer ( NSCLC) patients by FISH, and to analyze the relationship between
      ROS1 gene rearrangement and clinical features (including age, sex, stage,
      histology, smoking history) with NSCLC. METHODS: The ROS1 gene rearrangement in
      histological sections of 1 652 NSCLC tissues was detected by FISH. The extracted
      RNA was amplified and the sequences were analyzed by Sanger sequencing for ROS1
      positive samples. RESULTS: ROS1 rearrangement was identified in 53 specimens
      (3.2%) from the 1 652 NSCLC tissues. Among these positive cases, 15 were CD74
      ROS1, 13 were SLC34A2-ROS1, 13 were SDC4-ROS1 and 12 were TPM3-ROS1. The
      frequency of ROS1 rearrangement was significantly higher in never-smoking
      patients (49 cases) than in smokers (4 cases) (P < 0.05). Patients with ROS1
      positive NSCLC tended to be younger and there was no significant difference in
      sex (P > 0.05). All of the ROS1-positive samples were adenocarcinomas, with a
      tendency toward higher clinical stage (P < 0.05). CONCLUSIONS: ROS1 rearrangement
      has diversity, and may be defined as a new molecular subtype of NSCLC. ROS1
      rearrangement tends to occur in younger, and never-smoker lung adenocarcinoma
      patients.

PMID- 25567306
TI  - [Expression of Bcl-2 gene and its effect on prognosis of patients with primary
      gastrointestinal diffuse large B-cell lymphoma].
AB  - OBJECTIVE: To explore the expression of Bcl-2 mRNA and its effect on prognosis of
      patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL).
      METHODS: Real time quantitative PCR was used to determine the expression of Bcl-2
      mRNA in 40 PGI-DLBCL patients and 17 healthy controls. The association of Bcl-2
      expression with clinicopathological features and prognosis of the patients was
      analyzed. RESULTS: The expression level of Bcl-2 mRNA in PGI-DLBCL patients was
      1.03 +/- 0.93, significantly higher than that of the controls (0.41 +/- 0.21) (P
      < 0.05). The expression of Bcl-2 mRNA in stage IIE-IV patients (1.28 +/- 1.01)
      was significantly higher than that in the stage I-II2 patients (0.62 +/- 0.61) (P
      < 0.05). The expression of Bcl-2 mRNA in patients with international prognostic
      index (IPI) score >2 (1.95 +/- 1.27) was significantly higher than those with IPI
      score <= 2 (0.86 +/- 0.75)(P < 0.05). The expression of Bcl-2 mRNA in patients
      with complete remission (CR) (0.71 +/- 0.58) was significantly lower vs. 2.42 +/-
      0.91 in patients with no CR (P < 0.05). Univariate analysis indicated that beta2
      MG, IPI score>2, the Lugano staging, and Bcl-2 mRNA expression were associated
      with overall survival (OS) and progression-free survival (PFS) (P < 0.05).
      Multivariate analysis indicated that IPI score>2 was independently associated
      with OS (P < 0.05), and both IPI score >2 and Bcl-2 mRNA expression were
      independently associated with PFS (P < 0.05). CONCLUSIONS: The expression of Bcl
      2 mRNA in the tumor tissue of PGI-DLBCL patients is significantly higher than
      that in controls. PGI-DLBCL patients with higher expression of Bcl-2 have a poor
      chemotherapy response and inferior prognosis. IPI score >2 and higher expression
      of Bcl-2 mRNA are independent poor prognostic factors for PFS in PGI-DLBCL
      patients.

PMID- 25567307
TI  - [Detection and clinical implication of aneuploidy of chromosomes 11 and 20 in
      gastric adenocarcinoma].
AB  - OBJECTIVE: The aim of this study was to find out the value of chromosome
      aneuploidy in early diagnosis and prediction of postoperative recurrence of
      gastric adenocarcinoma (GAC). METHODS: Tissue samples, including 49 GAC, pairing
      pericancerous mucosa and normal gastric mucosa from the distant cutting margin
      were use in this study. Two centromere probes, Cen11 and Cen20 specific for
      chromosomes 11 and 20 were analyzed by FISH . The clinicopathological data were
      summarized. RESULTS: The incidence of aneuploidy of chromosome 11 in the tumors,
      pericancerous mucosa and normal gastric mucosa from the distant cutting margin
      were 83.7%, 40.8%, and 16.3%, respectively (P < 0.001), and those of chromosome
      20 were 87.8%, 53.1%, and 16.3%, respectively (P < 0.001). The aneuploidy of Cen
      11 displayed a significant correlation with Lauren's claasification, and lymph
      node metastasis (P < 0.05 for both). The pericancerous mucosa and normal gastric
      mucosa from the distant cutting margin displayed mainly chronic inflammatory
      changes, intestinal metaplasia and dysplasia. CONCLUSIONS: Aneuploidy of Cen11
      and Cen20 in pericancerous mucosa may be used as a candidate marker for early
      diagnosis of gastric adenocarcinoma and may have a predictive value of
      postoperative recurrence.

PMID- 25567308
TI  - [Comparison of the volume and localization of internal gross target volume and
      planning target volume delineated by clips and seroma based on 4D-CT scan for
      external-beam partial breast irradiation after breast conserving surgery].
AB  - OBJECTIVE: To explore the differences in volume and localization of the internal
      gross target volume and planning target volume delineated by clips and/or seroma
      based on four-dimensional computed tomography (4D-CT) during free-breathing in
      breast cancer patients after breast conserving surgery. METHODS: Fifteen breast
      cancer patients after breast-conserving surgery (BCS) were recruited for external
      beam partial breast irradiation (EB-PBI). On the ten sets CT images, the gross
      tumor volumes (GTV) formed by the clips, the seroma, and both the clips and
      seroma were delineated and defined as GTVc, GTVs and GTVc+s, respectively. Ten
      GTVc, GTVs and GTVc+s on the ten sets CT images produced the IGTVc, IGTVs,
      IGTVc+s. The PTVc, PTVs, PTVc+s were created by adding 15 mm to the IGTVc, IGTVs,
      IGTVc+s, respectively. The IGTV and PTV volume and distance between the centers
      of IGTVc, IGTVs, IGTVc+s and PTVc, PTVs, PTVc+s were all recorded. Conformity
      index (CI) and degree of inclusion (DI) were calculated for IGTV/IGTV and
      PTV/PTV, respectively. RESULTS: The volume of IGTVc+s[(35.73 +/- 19.77) cm3] was
      significantly larger than the IGTVc [(28.35 +/- 17.54) cm3] and IGTVs [(24.19 +/-
      21.53) cm3] (P < 0.05), and the volume of PTVc+s [(191.59 +/- 69.74) cm3] was
      significantly larger than that of the PTVc [(161.53 +/- 61.07) cm3] and PTVs
      [(148.98 +/- 62.22)cm3] (P < 0.05). There were significant differences between
      the DIs of IGTVc in IGTVc+s and IGTVc+s in IGTVc, the DIs of IGTVs in IGTVc+s and
      IGTVc+s in IGTVs, the DIs of PTVc in PTVc+s and PTVc+s in PTVc, and the DIs of
      PTVs vs. PTVc+s and PTVc+s in PTVs (P < 0.05 for all). The CI of IGTVc/IGTVc+s
      (0.63 +/- 0.14) and the CI of IGTVs/IGTVc+s (0.54 +/- 0.17) were significant
      larger than that of the CI of IGTVc/IGTVs (0.40 +/- 0.14)(P < 0.05). There were
      non-significant differences among the CI of PTVc/PTVs, PTVc/PTVc+s and
      PTVs/PTVc+s (0.73 +/- 0.12, 0.78 +/- 0.13 vs. 0.75 +/- 0.17). The DIs and CIs of
      IGTV/IGTV and PTV/PTV were negatively correlated with their centroid distance (P
      < 0.05). CONCLUSIONS: There are volume difference and spatial mismatch between
      the target volumes delineated on the basis of surgical clips and seroma. The DI
      and CI between the PTVs are larger than that between the IGTV. External-beam
      partial breast irradiation should be implemented based on the PTV that is defined
      based on both seroma and surgical clips.

PMID- 25567309
TI  - [Expression of multidrug resistance-associated proteins in different molecular
      subtypes of breast cancer and their correlation with hormone receptors and HER-].

PMID- 25567310
TI  - [Risk factors for Clostridium difficile-associated diarrhea among cancer
      patients].
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of Clostridium
      difficile (C. difficile) infection and the risk factors for acquisition of C.
      difficile-associated diarrhea (CDAD) among cancer patients who received
      chemotherapy or radiation therapy. METHODS: We analyzed 277 stool samples from
      cancer patients with diarrhea between Sep 2010 and Dec 2011 in our hospital.
      Stool C. difficile toxin A/B test, stool culture for C. difficile and routine
      stool examination were performed. In addition, the risk factors for CDAD were
      investigated in a set of 41 C. difficile toxin-positive cancer patients and 82
      matched C. difficile toxin-negative controls by univariate analysis and
      multivariate analysis. RESULTS: Out of a total of 277 cancer patients with
      diarrhea, 41 (14.8%) were C. difficile toxin-positive. Among these 41 cases, 11
      (26.8%, 11/41) were C. difficile culture-positive. Univariate analysis showed
      that antibiotics use (P = 0.853), proton pump inhibitor use (P = 0.718),
      hypoproteinemia (P = 0.139) and white blood cell count (P = 0.454) did not appear
      to be associated with acquisition of CDAD in cancer patients. However, receiving
      chemotherapy (P = 0.023), receiving radiotherapy (P = 0.003), a positive fecal
      occult blood test result (P = 0.005) and the presence of fecal leukocytes (P =
      0.007) showed close association with acquisition of CDAD in cancer patients.
      Multivariate analysis showed that receiving chemotherapy (OR, 8.308; 95% CI,
      1.997-34.572; P = 0.004) and a positive result of fecal occult blood test (OR,
      8.475; 95% CI, 1.463-49.109; P = 0.017) were independent risk factors for
      acquisition of CDAD among cancer patients. CONCLUSIONS: Our results support that
      receiving chemotherapy and a positive fecal occult blood test result are
      independent risk factors for acquisition of CDAD among cancer patients. Cancer
      patients who are at high-risk for CDAD should take stool C. difficile toxin A/B
      test and stool culture for C. difficile regularly and prevention of CDAD.

PMID- 25567311
TI  - [Concurrent chemotherapy with different dose regimens of cisplatin for
      nasopharyngeal carcinoma using intensity-modulated radiation therapy: a phase II
      prospective randomized controlled trial].
AB  - OBJECTIVE: To explore the acute toxic effects and early curative efficacy of
      concurrent chemotherapy with different doses of cisplatin for Chinese
      nasopharyngeal carcinoma (NPC) patients using intensity-modulated radiation
      therapy (IMRT). METHODS: Eighty-eight untreated stage II/III nasopharyngeal
      cancer patients receiving IMRT and concurrent cisplatin were randomized into two
      groups receiving different doses of cisplatin. The standard group (DDP 100 mg/m2
      q3w, n = 44) and the study group (DDP 80 mg/m2 q3w, n = 44). The acute toxic
      effects and 3-month therapeutic efficacy (early curative efficacy) in patients of
      the two groups who completed treatment were compared and analyzed. RESULTS:
      During the treatment, grade III-IV acute toxic effects were observed in more
      patients of the standard group compared with that in the study group (72.7% vs.
      59.1%), but the difference was statistically not significant (P = 0.18).
      Significant difference was only seen in upper gastrointestinal reaction (P =
      0.01) and anemia (P = 0.03) among the non-hematological and hematological adverse
      events. No significant differences in other adverse events were found between the
      two groups (P < 0.05). Three months after the completion of radiotherapy, 80
      cases of the whole group achieved complete remission (CR) in the nasopharynx and
      neck MRI. In both the standard group and study group, 40 patients had CR and 4
      patients had residual disease, respectively, showing a non-significant difference
      (P = 0.51) between the two groups. CONCLUSIONS: During the IMRT course, patients
      received cisplatin 80 mg/m2 q3w, experienced less grade III-IV acute toxic
      effects. Concurrent chemoradiotherapy with cisplatin 80 mg/m2 q3w or 100 mg/m2
      q3w, demonstrate similar early curative efficacy in II/III stage NPC patients in
      endemic regions of China.

PMID- 25567312
TI  - [Prognostic significance of the number of positive lymph nodes, number of
      involved regions and metastatic lymph node ratio in hypopharyngeal cancer].
AB  - OBJECTIVE: To explore the relationship between positive lymph node number,
      involved region, positive lymph node ratio and the prognosis of patients with
      hypopharyngeal cancer. METHODS: Clinicopatological data of 81 patients with
      hypopharyngeal squamous cell carcinoma who underwent hypopharyngectomy and
      cervical lymph node dissection from January 2000 to December 2005 in our hospital
      were analyzed retrospectively. The relationship between positive lymph node
      number, involved region, positive lymph node ratio and the prognosis was
      analyzed. RESULTS: The rate of lymph node metastasis was 79.0% (64/81) in the 81
      patients with hypopharyngeal cancer. Of which, the rates of unilateral metastasis
      and bilateral metastasis were 82.9% (53/64) and 17.1% (11/64), respectively. The
      rate of lymph node metastasis was increasing with advancing tumor stage. The
      median survival times were 81, 51 and 26 months in the patients with 0, 1-3 and
      >= 4 positive lymph nodes, respectively (P < 0.001), 84, 45 and 23 months in
      patients with 0, 1-2 and >= 3 involved regions, respectively (P < 0.001), and 84,
      51 and 17 months in patients with positive lymph node ratio of 0, <10% and >=
      10%, respectively (P < 0.001). Multivariable analysis showed that positive lymph
      node ratio, extracapsular infiltration, T classification and treatment modality
      were independent prognostic factors (P = 0.002). CONCLUSIONS: Positive lymph node
      ratio is an independent prognostic factor for hypopharyngeal cancer.

PMID- 25567314
TI  - [Comparison of clinical characteristics of differentiated thyroid carcinoma in
      children, adolescents and young adults].

PMID- 25567313
TI  - [Comparison of the effectiveness of platinum-based chemotherapy versus non
      platinum-based chemotherapy for triple-negative breast cancer with metastases
      confined to the lungs].
AB  - OBJECTIVE: To compare the effect of first-line treatment with platinum-based
      chemotherapy and non-platinum-based chemotherapy in patients with lung metastases
      from triple negative breast cancer (TNBC). METHODS: Sixty-five eligible patients
      were divided into platinum-treated group and non-platinum-treated group according
      to the first-line therapy. Factors predicting the chemotherapeutic efficacy
      included overall survival (OS), progression-free survival (PFS) and objective
      response (OR). RESULTS: In the platinum-treated group of 32 patients, 2 cases
      (6.3%) achieved CR, 16 cases (50.0%) achieved PR, 11 (34.4%) cases achieved SD,
      and 3 patients (9.4%) achieved PD. In the non-platinum-treated group of 33
      patients, 2 cases (6.1%) achieved CR, 6 cases (18.2%) achieved PR, 16 cases
      (48.5%) achieved SD, and 9 cases (27.3%) achieved PD. Median PFS was
      significantly longer in the platinum-treated group than in the non-platinum
      treated group (10 months vs. 6.0 months, P = 0.012), and OS was also improved (32
      months vs. 22 months, P = 0.006). Multivariate analysis of several factors
      including local-regional lymph node involvement, lung metastasis-related
      symptoms, first-line platinum-based chemotherapy, disease-free interval, size and
      number of lung lesions, showed that first-line platinum-based chemotherapy was an
      independent prognostic factor for TNBC patients with lung metastases.
      CONCLUSIONS: Compared with non-platinum-based chemotherapy, the first-line
      platinum-based chemotherapy can improve PFS and OS in TNBC patients with
      metastases confined to the lungs.

PMID- 25567315
TI  - [Efficacy of percutaneous transhepatic cholangial drainage in the treatment of
      periampullary carcinoma complicated with acute cholangitis of severe type].

PMID- 25567316
TI  - [Trend analysis of the changes of male/female, urban/rural incidences and average
      age of cancer patients in China 1989-2008].
AB  - OBJECTIVE: To analyze the changes of male/female and urban/rural incidences and
      average age of cancer diagnosis over the period 1989-2008 in China. METHODS: All
      cancer incident cases from 1989 to 2008 in registration areas were retrieved from
      the National Central Cancer Registry database. Data were stratified by sex
      (male/female) and area (urban/rural) and age group (19 age groups, including 0, 1
      4, 5-9, 5-84 by 5, >= 85). Poisson regression was used to analyze the differences
      in incidence rates between males and females, urban and rural areas with 95%
      confident intervals and P values adjusted by age. The average age of cancer
      diagnosis was calculated every year. All trends were analyzed by linear
      regression. RESULTS: The ratio of male to female cancer incidences was 1.56 in
      1989 and 1.35 in 2008. The ratio of urban to rural incidences was 0.89 in 1998
      and increased to 0.98 in 2008. The average age of cancer diagnosis was 61.96
      years old for men and 60.15 for women in 1989, compared with 64.87 and 61.81
      years in 2008, respectively. The disparities in sex and areas have been
      decreasing in recent 20 years. The cancer patients tend to getting older. These
      trends were all significant. CONCLUSIONS: The cancer incidences in male/female
      populations and different areas have apparent disparities over the 1989-2008
      period in China. However, the differences are narrowing and the average age is
      increasing. In the making of an efficient anti-cancer strategy, we should also
      take consideration of the differences of cancer burden in different population
      groups in our country.

PMID- 25567317
TI  - Superior intrinsic thermoelectric performance with zT of 1.8 in single-crystal
      and melt-quenched highly dense Cu(2-x)Se bulks.
AB  - Practical applications of the high temperature thermoelectric materials developed
      so far are partially obstructed by the costly and complicated fabrication
      process. In this work, we put forward two additional important properties for
      thermoelectric materials, high crystal symmetry and congruent melting. We propose
      that the recently discovered thermoelectric material Cu2-xSe, with figure of
      merit, zT, over 1.5 at T of ~ 1000 K, should meet these requirements, based on
      our analysis of its crystal structure and the Cu-Se binary phase diagram. We
      found that its excellent thermoelectric performance is intrinsic, and less
      dependent on grain size, while highly dense samples can be easily fabricated by a
      melt-quenching approach. Our results reveal that the melt-quenched samples and
      single crystals exhibit almost the same superior thermoelectric performance, with
      zT as high as 1.7-1.8 at T of ~973 K. Our findings not only provide a cheap and
      fast fabrication method for highly dense Cu(2-x)Se bulks with superior
      thermoelectric performance, paving the way for possible commercialization of Cu2
      xSe as an outstanding component in practical thermoelectric modules, but also
      provide guidance in searching for new classes of thermoelectric systems with high
      crystal symmetry or further improving the cost performance of other existing
      congruent-melting thermoelectric materials.

PMID- 25567318
TI  - Prevalence and correlates of young people's sexual aggression perpetration and
      victimisation in 10 European countries: a multi-level analysis.
AB  - Data are presented on young people's sexual victimisation and perpetration from
      10 European countries (Austria, Belgium, Cyprus, Greece, Lithuania, the
      Netherlands, Poland, Portugal, Slovakia and Spain) using a shared measurement
      tool (N = 3480 participants, aged between 18 and 27 years). Between 19.7 and
      52.2% of female and between 10.1 and 55.8% of male respondents reported having
      experienced at least one incident of sexual victimisation since the age of
      consent. In two countries, victimisation rates were significantly higher for men
      than for women. Between 5.5 and 48.7% of male and 2.6 and 14.8% of female
      participants reported having engaged in a least one act of sexual aggression
      perpetration, with higher rates for men than for women in all countries.
      Victimisation rates correlated negatively with sexual assertiveness and
      positively with alcohol use in sexual encounters. Perpetration rates correlated
      positively with attitudes condoning physical dating violence and with alcohol use
      in men, and negatively with sexual assertiveness in women. At the country level,
      lower gender equality in economic power and in the work domain was related to
      higher male perpetration rates. Lower gender equality in political power and
      higher sexual assertiveness in women relative to men were linked to higher male
      victimisation rates. 

PMID- 25567319
TI  - Aged iPSCs display an uncommon mitochondrial appearance and  fail to undergo in
      vitro neurogenesis.
AB  - Reprogramming of human fibroblasts into induced pluripotent stem cells (iPSCs)
      leads to mitochondrial rejuvenation, making iPSCs a candidate model to study the
      mitochondrial biology during stemness and differentiation. At present, it is
      generally accepted that iPSCs can be maintained and propagated indefinitely in
      culture, but no specific studies have addressed this issue. In our study, we
      investigated features related to the 'biological age' of iPSCs, culturing and
      analyzing iPSCs kept for prolonged periods in vitro. We have demonstrated that
      aged iPSCs present an increased number of mitochondria per cell with an altered
      mitochondrial membrane potential and fail to properly undergo in vitro
      neurogenesis. In aged iPSCs we have also found an altered expression of genes
      relevant to mitochondria biogenesis. Overall, our results shed light on the
      mitochondrial biology of young and aged iPSCs and explore how an altered
      mitochondrial status may influence neuronal differentiation. Our work suggests to
      deepen the understanding of the iPSCs biology before considering their use in
      clinical applications.

PMID- 25567320
TI  - Doxorubicin-loaded microgels composed of cinnamic acid-gelatin conjugate and
      cinnamic acid-Pluronic F127 conjugate.
AB  - Microgels were prepared by cinnamic acid-gelatin (type B) conjugate (CA-GelB) and
      cinnamic acid-Pluronic F127 conjugate (CA-Plur). (1)H NMR confirmed that CA was
      conjugated to gelatin and the gelatin to CA residue molar ratio was estimated to
      be 1:4.7 by a colorimetric method. CA-Plur of which the CA residue to Plur molar
      ratio was 1.2:1 was used as a thermo-sensitive polymer. The CA residues of CA
      Plur/CA-GelB mixture were readily photo-dimerized to form microgels by UV
      irradiation. The isoelectric point of the microgel was found to be pH 5.8 and the
      hydrodynamic diameter decreased when the suspension temperature increased. The
      microgel could hardly retard the release of doxorubicin (DOX) at pH 3.0 and pH
      5.0, but it could suppress and control the release at pH 7.4 possibly due to
      electrostatic attraction. Meanwhile, the release of DOX at pH 7.4 was less
      suppressed when the medium temperature was higher, possibly because of thermal
      thinning of Pluronic chain layer. 

PMID- 25567321
TI  - Dopaminergic modulation of motor network dynamics in Parkinson's disease.
AB  - Although characteristic motor symptoms of Parkinson's disease such as
      bradykinesia typically improve under dopaminergic medication, deficits in higher
      motor control are less responsive. We here investigated the dopaminergic
      modulation of network dynamics underlying basic motor performance, i.e. finger
      tapping, and higher motor control, i.e. internally and externally cued movement
      preparation and selection. Twelve patients, assessed ON and OFF medication, and
      12 age-matched healthy subjects underwent functional magnetic resonance imaging.
      Dynamic causal modelling was used to assess effective connectivity in a motor
      network comprising cortical and subcortical regions. In particular, we
      investigated whether impairments in basic and higher motor control, and the
      effects induced by dopaminergic treatment are due to connectivity changes in (i)
      the mesial premotor loop comprising the supplementary motor area; (ii) the
      lateral premotor loop comprising lateral premotor cortex; and (iii) cortico
      subcortical interactions. At the behavioural level, we observed a marked slowing
      of movement preparation and selection when patients were internally as opposed to
      externally cued. Preserved performance during external cueing was associated with
      enhanced connectivity between prefrontal cortex and lateral premotor cortex OFF
      medication, compatible with a context-dependent compensatory role of the lateral
      premotor loop in the hypodopaminergic state. Dopaminergic medication
      significantly improved finger tapping speed in patients, which correlated with a
      drug-induced coupling increase of prefrontal cortex with the supplementary motor
      area, i.e. the mesial premotor loop. In addition, only in the finger tapping
      condition, patients ON medication showed enhanced excitatory influences exerted
      by cortical premotor regions and the thalamus upon the putamen. In conclusion,
      the amelioration of bradykinesia by dopaminergic medication seems to be driven by
      enhanced connectivity within the mesial premotor loop and cortico-striatal
      interactions. In contrast, medication did not improve internal motor control
      deficits concurrent to missing effects at the connectivity level. This
      differential effect of dopaminergic medication on the network dynamics underlying
      motor control provides new insights into the clinical finding that in Parkinson's
      disease dopaminergic drugs especially impact on bradykinesia but less on
      executive functions. 

PMID- 25567322
TI  - Imbalance in habitual versus goal directed neural systems during symptom
      provocation in obsessive-compulsive disorder.
AB  - Intrusive thoughts and compulsive urges to perform stereotyped behaviours are
      typical symptoms of obsessive-compulsive disorder. Emerging evidence suggests a
      cognitive bias towards habit formation at the expense of goal-directed
      performance in obsessive-compulsive disorder. In this study, we test this
      hypothesis using a novel individualized ecologically valid symptom provocation
      design: a live provocation functional magnetic resonance imaging paradigm with
      synchronous video-recording of behavioural avoidance responses. By pairing
      symptom provocation with online avoidance responses on a trial-by-trial basis, we
      sought to investigate the neural mechanisms leading to the compulsive avoidance
      response. In keeping with the model of habit formation in obsessive-compulsive
      disorder, we hypothesized that this disorder would be associated with lower
      activity in regions implicated in goal-directed behaviours and higher activity in
      regions implicated in habitual behaviours. Fifteen patients with obsessive
      compulsive disorder and 15 healthy control volunteers participated in this
      functional magnetic resonance imaging study. Online stimuli were individually
      tailored to achieve effective symptom provocation at neutral, intermediate and
      strong intensity levels. During the symptom provocation block, the participant
      could choose to reject or terminate the provoking stimuli resulting in cessation
      of the symptom provocation. We thus separately analysed the neural correlates of
      symptom provocation, the urge to avoid, rejection and relief. Strongly symptom
      provoking conditions evoked a dichotomous pattern of deactivation/activation in
      patients, which was not observed either in control conditions or in healthy
      subjects: a deactivation of caudate-prefrontal circuits accompanied by
      hyperactivation of subthalamic nucleus/putaminal regions. This finding suggests a
      dissociation between regions engaged in goal-directed and habitual behaviours.
      The putaminal hyperactivity during patients' symptom provocation preceded
      subsequent deactivation during avoidance and relief events, indicating a pivotal
      role of putamen in regulation of behaviour and habit formation in obsessive
      compulsive disorder. Effective connectivity analysis identified the ventromedial
      prefrontal cortex/orbitofrontal cortex as the main structure in this circuitry
      involved in the modulation of compulsivity in obsessive-compulsive disorder.
      These findings suggest an imbalance in circuitry underlying habitual and goal
      directed action control, which may represent a fundamental mechanism underlying
      compulsivity in obsessive-compulsive disorder. Our results complement current
      models of symptom generation in obsessive-compulsive disorder and may enable the
      development of future therapeutic approaches that aim to alleviate this
      imbalance. 

PMID- 25567324
TI  - Inhibitor development in haemophilia according to concentrate. Four-year results
      from the European HAemophilia Safety Surveillance (EUHASS) project.
AB  - Inhibitor development represents the most serious side effect of haemophilia
      treatment. Any difference in risk of inhibitor formation depending on the product
      used might be of clinical relevance. It was this study's objective to assess
      inhibitor development according to clotting factor concentrate in severe
      haemophilia A and B. The European Haemophilia Safety Surveillance (EUHASS) was
      set up as a study monitoring adverse events overall and according to concentrate.
      Since October 2008, inhibitors were reported at least quarterly. Number of
      treated patients was reported annually, specifying the number of patients
      completing 50 exposure days (Previously Untreated Patients, PUPs) without
      inhibitor development. Cumulative incidence, incidence rates and 95 % confidence
      intervals (CI) were calculated. Data from October 1, 2008 to December 31, 2012
      were analysed for 68 centres that validated their data. Inhibitors developed in
      108/417 (26 %; CI 22-30 %) PUPs with severe haemophilia A and 5/72 (7 %; CI 2
      16%) PUPs with severe haemophilia B. For Previously Treated Patients (PTPs), 26
      inhibitors developed in 17,667 treatment years [0.15/100 treatment years; CI 0.10
      0.22) for severe haemophilia A and 1/2836 (0.04/100; (CI 0.00-0.20) for severe
      haemophilia B. Differences between plasma-derived and recombinant concentrates,
      or among the different recombinant FVIII concentrates were investigated. In
      conclusion, while confirming the expected rates of inhibitors in PUPs and PTPs,
      no class or brand related differences were observed.

PMID- 25567325
TI  - Automated alerts for acute kidney injury warrant caution.

PMID- 25567323
TI  - Neuroinflammation, mitochondrial defects and neurodegeneration in
      mucopolysaccharidosis III type C mouse model.
AB  - Severe progressive neurological paediatric disease mucopolysaccharidosis III type
      C is caused by mutations in the HGSNAT gene leading to deficiency of acetyl-CoA:
      alpha-glucosaminide N-acetyltransferase involved in the lysosomal catabolism of
      heparan sulphate. To understand the pathophysiology of the disease we generated a
      mouse model of mucopolysaccharidosis III type C by germline inactivation of the
      Hgsnat gene. At 6-8 months mice showed hyperactivity, and reduced anxiety.
      Cognitive memory decline was detected at 10 months and at 12-13 months mice
      showed signs of unbalanced hesitant walk and urinary retention. Lysosomal
      accumulation of heparan sulphate was observed in hepatocytes, splenic sinus
      endothelium, cerebral microglia, liver Kupffer cells, fibroblasts and pericytes.
      Starting from 5 months, brain neurons showed enlarged, structurally abnormal
      mitochondria, impaired mitochondrial energy metabolism, and storage of densely
      packed autofluorescent material, gangliosides, lysozyme, phosphorylated tau, and
      amyloid-beta. Taken together, our data demonstrate for the first time that
      deficiency of acetyl-CoA: alpha-glucosaminide N-acetyltransferase causes
      lysosomal accumulation of heparan sulphate in microglial cells followed by their
      activation and cytokine release. They also show mitochondrial dysfunction in the
      neurons and neuronal loss explaining why mucopolysaccharidosis III type C
      manifests primarily as a neurodegenerative disease. 

PMID- 25567327
TI  - Bone morphogenetic protein 2 gene transduction enhances the osteogenic potential
      of human urine-derived stem cells.
AB  - INTRODUCTION: Urine-derived stem cells (USCs) have the ability to differentiate
      into osteogenic lineage. Previous studies have raised the possibility that USCs
      could be used for bone repair. To harness the power of USCs in promoting bone
      regeneration, methods must be developed to induce USCs to osteogenic lineage
      efficiently. The present study investigates the effect of lentivirus-encoded bone
      morphogenetic protein 2 (BMP2) gene transduction on the osteogenic potential of
      USCs. METHODS: USCs were isolated from voided urine and transduced with
      Lentiviral vector encoding BMP2. An in vitro study was performed to detect
      Lentiviral-BMP2 transduced USCs differentiated towards osteogenic lineage.
      Furthermore, Lentiviral-BMP2 transduced USCs were transplanted in vivo to examine
      the ectopic bone formation ability. After six weeks, retrieval samples were
      obtained for immunostaining and histological analysis. RESULTS: The results
      showed that the transduction efficiencies were over 90%, and transduced USCs had
      high expression levels of the BMP2 gene and secreted BMP2 protein. Alkaline
      activity and mineral deposition staining demonstrated that transduced USCs
      differentiate into osteogenic lineages without the addition of osteogenic
      supplements. Transduced USCs also showed high expression of bone-related markers,
      including runt-related protein-2 (Runx2) and osteocalcin (OCN), confirming this
      lentiviral-BMP2 construct provides sufficient stimuli for osteogenic
      differentiation. Histological analysis indicated that the transduced USCs induced
      robust new bone formation in nude mice. Six weeks after transplantation, human
      derived cells were observed to participate in bone formation. CONCLUSIONS: These
      results demonstrate that BMP2 gene transduction provides an effective method to
      enhance the osteogenic potential of USCs.

PMID- 25567328
TI  - Survival analysis of 272 patients with pancreatic cancer undergoing combined
      treatment.
AB  - BACKGROUND: In China, traditional Chinese herbal medicine (TCHM) has been widely
      used for pancreatic cancer. This retrospective, matched case-control study aimed
      to assess factors affecting the survival time of patients with pancreatic cancer.
      METHODS: From 2004 to 2012, a total of 411 patients with pathologically confirmed
      pancreatic cancer were enrolled, and 272 patients were matched and divided into
      TCHM and non-TCHM groups (control group) based on received TCHM or not. The match
      was according to gender, age of onset, radiotherapy, and chemotherapy. Both
      groups received comprehensive treatments, the TCHM group simultaneously received
      the TCHM spleen-invigorating compound for more than 3 months. The Cox model was
      used for prognostic factor analysis and the Kaplan-Meier method for estimating
      median overall survival (OS) and disease-free survival (DFS). RESULTS: In 130
      patients with advanced pancreatic cancer, COX analysis showed the Karnofsky
      Performance Scale (KPS; P = .000), radiotherapy (P = .003), and TCHM (P = .001)
      were independent prognostic factors for OS, with median OS of 12.7 and 9.9 months
      in TCHM and non-TCHM groups, respectively (hazard ratio [HR] = 0.520; 95%
      confidence interval [CI] = 0.353-0.766; P = .033). In 142 patients undergoing
      radical surgery, KPS (P = .000) and TCHM (P = .000) were independent prognostic
      factors for OS and DFS, median OS was 23.8 and 12.4 months in TCHM and non-TCHM
      groups, respectively (HR = 0.373; 95% CI = 0.251-0.554; P = .000), and the median
      DFS was 21.5 and 10.2 months in TCHM and non-TCHM groups, respectively (HR =
      0.352; 95% CI = 0.237-0.522; P = .000). CONCLUSIONS: KPS was an important
      prognostic factor of pancreatic cancer. Spleen-invigorating compounds could have
      an effect on improving the prognosis of pancreatic cancer patients.

PMID- 25567326
TI  - 15-epi-lipoxin A4 reduces the mortality of prematurely born pups in a mouse model
      of infection-induced preterm birth.
AB  - Preterm birth remains the leading cause of neonatal mortality and morbidity
      worldwide. There are currently few effective therapies and therefore an urgent
      need for novel treatments. Although there is much focus on trying to alter
      gestation of delivery, the primary aim of preterm birth prevention therapies
      should be to reduce prematurity related mortality and morbidity. Given the link
      between intrauterine infection and inflammation and preterm labour (PTL), we
      hypothesized that administration of lipoxins, key anti-inflammatory and pro
      resolution mediators, could be a useful novel treatment for PTL. Using a mouse
      model of infection-induced PTL, we investigated whether 15-epi-lipoxin A4 could
      delay lipopolysaccharide (LPS)-induced PTL and reduce pup mortality. On D17 of
      gestation mice (n = 9-12) were pretreated with vehicle or 15-epi-lipoxin A4 prior
      to intrauterine administration of LPS or PBS. Although pretreatment with 15-epi
      lipoxin A4 did not delay LPS-induced PTL, there was a significant reduction in
      the mortality amongst prematurely delivered pups (defined as delivery within 36 h
      of surgery) in mice treated with 15-epi-lipoxin A4 prior to LPS treatment,
      compared with those receiving LPS alone (P < 0.05). Quantitative real-time (QRT)
      PCR analysis of utero-placental tissues harvested 6 h post-treatment demonstrated
      that 15-epi-lipoxin A4 treatment increased Ptgs2 expression in the uterus,
      placenta and fetal membranes (P < 0.05) and decreased 15-Hpgd expression (P <
      0.05) in the placenta and uterus, suggesting that 15-epi-lipoxin A4 may regulate
      the local production and activity of prostaglandins. These data suggest that
      augmenting lipoxin levels could be a useful novel therapeutic option in the
      treatment of PTL, protecting the fetus from the adverse effects of infection
      induced preterm birth. 

PMID- 25567329
TI  - Do yoga and aerobic exercise training have impact on functional capacity,
      fatigue, peripheral muscle strength, and quality of life in breast cancer
      survivors?
AB  - AIM: The aim of the study was to compare the effects of aerobic exercise training
      and yoga on the functional capacity, peripheral muscle strength, quality of life
      (QOL), and fatigue in breast cancer survivors. MATERIAL AND METHODS: A total of
      52 patients with a diagnosis of breast cancer were included in the study. The
      patients were randomly assigned to 2 groups: aerobic exercise (n = 28) and yoga
      added to aerobic exercise (n = 24). Both groups participated in submaximal
      exercise 30 minutes/d, 3 d/wk for 6 weeks. The second group participated in a 1
      hour yoga program in addition to aerobic exercise training. Functional capacity
      was assessed by the 6-Minute Walk Test (6MWT). Peripheral muscle strength was
      evaluated with a hand-held dynamometer. The fatigue severity level was assessed
      with the Fatigue Severity Scale (FSS). The QOL was determined by the European
      Organisation for Research and Treatment of Cancer Quality of Life Questionnaire.
      RESULTS: There were statistically significant increases in peripheral muscle
      strength, the 6MWT distance, and the perception of QOL in both groups (P < .05).
      Additionally, the group with aerobic exercise and yoga showed marked improvement
      compared with the aerobic exercise group in fatigue perception (P < .05).
      CONCLUSION: According to the data from this study, aerobic exercise training and
      yoga improved the functional capacity and QOL of breast cancer patients. Aerobic
      exercise programs can be supported by body mind techniques, such as yoga, in the
      rehabilitation of cancer patients for improving functional recovery and
      psychosocial wellness.

PMID- 25567332
TI  - Editorial. Current topics in sepsis.

PMID- 25567334
TI  - Oral inflammation and bacteremia: implications for chronic and acute systemic
      diseases involving major organs.
AB  - Gingivitis and periodontitis are both highly prevalent gum diseases characterized
      by an accumulation of a polymicrobial biofilm (dental plaque) around teeth and
      inflammation in adjacent soft tissues. During dental procedures, even tooth
      brushing, these bacteria and their components, such as endotoxin, can easily
      disseminate into the systemic circulation through minor or major gingival
      injuries. Particularly in immuno-compromised subjects or patients with
      preexisting pathologic conditions, bacteremia may lead to bacterial infection of
      distant organs, which may cause immunological reactions. Oral bacteria and
      endotoxins have been found in sepsis, infective endocarditis, lung infection,
      liver disease and many other potentially lethal disorders. This article presents
      a review of the possible pathologic consequences of bacteremia originating in the
      oral cavity and points out the most commonly affected organs as well as
      preventive and treatment measures. At the present time, plaque control by
      subjects and/or dental professionals is one of the most effective means to
      prevent the onset and progression of oral bacteremia-induced systemic diseases. 

PMID- 25567333
TI  - Involvement of hypoxia-inducible factors in the dysregulation of oxygen
      homeostasis in sepsis.
AB  - Sepsis is a state of infection with serious systemic manifestations, and if
      severe enough, can be associated with multiple organ dysfunction and systemic
      hypotension, which can cause tissues to be hypoxic. Inflammation, as part of the
      multifaceted biological response to injurious stimuli, such as pathogens or
      damaged tissues and cells, underlies these biological processes. Prolonged and
      persistent inflammation, also known as chronic inflammation, results in
      progressive alteration in the various types of cells at the site of inflammation
      and is characterized by the simultaneous destruction and healing of tissue during
      the process. Tissue hypoxia during inflammation is not just a simple bystander
      process, but can considerably affect the development or attenuation of
      inflammation by causing the regulation of hypoxia-dependent gene expression.
      Indeed, the study of transcriptionally regulated tissue adaptation to hypoxia
      requires intense investigation to help control hypoxia-induced inflammation and
      organ failure. In this review, I have described the pathophysiology of sepsis
      with respect to oxygen metabolism and expression of hypoxia-inducible factor 1. 

PMID- 25567336
TI  - Extracorporeal lung assist for sepsis and acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is one of the major causes of ICU
      deaths. Extracorporeal lung assist (ECLA) has been used as a rescue therapy for
      most severe form of ARDS. However, its survival benefit had not been shown until
      CESAR trial in 2009. This has been because the concept of lung protective
      ventilation strategy had not yet known. Since CESAR trial, the clinical
      application of ECLA for ARDS as a method to achieve lung rest has wide spread.
      The effectiveness is further appreciated during the 2009 H1N1 influenza pandemic.
      The succeeded countries achieved building the transportation systems to collect
      ECLA patients. With the accumulating evidences of survival benefit, the long-term
      outcome such as pulmonary function and quality of life are in concern.
      PumplessECLA which is a newly developed form of ECLA is also reviewed. In this
      essay we will firstly review the basics of ARDS and ECLA. Then the historical
      development of ECLA evidences for ARDS are reviewed. 

PMID- 25567335
TI  - Sepsis pathophysiology and anesthetic consideration.
AB  - Sepsis remains to be a significant health care issue associated with high
      mortality and healthcare cost, despite the extensive effort to better understand
      the pathophysiology of the sepsis. Recently updated clinical guideline for severe
      sepsis and septic shock, "Surviving Sepsis Campaign 2012", emphasizes the
      importance of early goal-directed therapy, which can be implemented in
      intraoperative management of sepsis patients. Herein, we review the updates of
      current guideline and discuss its application to anesthesic management.
      Furthermore, we review the recent advance in knowledge of sepsis pathophysiology,
      focusing on immune modulation, which may lead to new clinical therapeutic
      approach to sepsis. 

PMID- 25567337
TI  - Mechanical ventilation for ARDS patients--for a better understanding of the 2012
      Surviving Sepsis Campaign Guidelines.
AB  - The mortality rate among patients suffering acute respiratory distress syndrome
      (ARDS) remains high despite implementation at clinical centers of the lung
      protective ventilatory strategies recommended by the International Guidelines for
      Management of Severe Sepsis and Septic Shock, 2012. This suggests that such
      strategies are still sub-optimal for some ARDS patients. For these patients,
      tailored use of ventilator settings should be considered, including: further
      reduction of tidal volumes, administration of neuromuscular blocking agents if
      the patient's spontaneous breathing is incompatible with mechanical ventilation,
      and adjusting positive end-expiratory pressure (PEEP) settings based on
      transpulmonary pressure levels. 

PMID- 25567339
TI  - Neuroinflammation in sepsis: sepsis associated delirium.
AB  - Sepsis-associated delirium (SAD) is a clinical manifestation of the involvement
      of the central nervous system (CNS) during sepsis. The purpose of this review is
      to provide a concise overview of SAD including the epidemiology and current
      diagnostic criteria for SAD. We present in detail the pathophysiology with
      regards to blood-brain-barrier breakdown, cytokine activation and
      neurotransmitter deregulation. Treatment and prognosis for SAD are also briefly
      discussed. SAD is the most common form of delirium acquired in the ICU (Intensive
      Care Unit), and is described in about 50% of septic patients. Clinical features
      include altered level of consciousness, reduced attention, change in cognition
      and perceptual disturbances. Symptoms can reversible, but prolonged deficits can
      be observed in older patients. Pathophysiology of SAD is poorly understood, but
      involves microvascular, metabolic and, not least, inflammatory mechanisms leading
      to CNS dysfunction. These mechanisms can be different in SAD compared to ICU
      delirium associated with other conditions. SAD is diagnosed clinically using
      validated tools such as CAM-ICU (Confusion Assessment Method for the Intensive
      Care Medicine) or ICDSC (The Intensive Care Delirium Screening Checklist), which
      have good specificity but low sensitivity. Neuroimaging studies and EEG
      (Electroencephalography) can be useful complement to clinical evaluation to
      define the severity of the condition. Prompt diagnosis and eradication of septic
      foci whenever possible is vital. Preventive measures for SAD in the critically
      ill patient requiring long-term sedation include maintaining light levels of
      sedation using non-benzodiazepine sedatives (either propofol or dexmedetomidine).
      Early mobilization of patients in the ICU is also recommended. Antipsychotic
      drugs (haloperidol and atypical antipsychotics) are widely used to treat SAD, but
      firm evidence of their efficacy is lacking. 

PMID- 25567340
TI  - Changes of expression of the protein C pathway components in LPS-induced
      endotoxemia--implication for sepsis.
AB  - The process of blood coagulation is mediated by activation of a series of serine
      protease zymogens. The protein C (PC) anticoagulant pathway, one of the important
      pathways related to physiological thrombosis formation, includes PC,
      thrombomodulin (TM), endothelial PC receptor (EPCR), protein S (PS) and C4b
      binding protein (C4BP). TM, mainly present in endothelial cells, is a cofactor
      for thrombin-catalyzed activation of PC, and the resulting activated PC (aPC)
      inactivates the blood coagulation cofactors factor Va and factor VIIIa in the
      presence of PS. PS, mainly synthesized in hepatocytes and endothelial cells,
      plays a critical role as a cofactor of anticoagulant aPC in the regulation of
      blood coagulation. The cofactor activity of PS for aPC is regulated by C4BP, a
      multimeric protein whose structure consists of seven alpha-chains (C4BPalpha) and
      a beta-chain (C4BPbeta). Sepsis is generally caused by infection by
      microorganisms, and patients with sepsis undergo drastic hemostatic changes,
      thought to be induced by lipopolysaccharide (LPS) and inflammatory cytokines. In
      this review, based primarily on our previous studies, we describe the LPS- and
      cytokine-induced changes in various proteins in the PC anticoagulant pathway that
      are related to the increased risk of thrombosis under sepsis. Furthermore, we
      discuss the potential of recombinant soluble TM (rsTM) as a possible remedy for
      sepsis. 

PMID- 25567341
TI  - Meet the new Hormones and Cancer editorial team: Gary D. Hammer, Associate
      Editor.

PMID- 25567338
TI  - Neutrophil migration under normal and sepsis conditions.
AB  - Neutrophil migration is critical for pathogen clearance and host survival during
      severe sepsis. Interaction of neutrophil adhesion receptors with ligands on
      endothelial cells results in firm adhesion of the circulating neutrophils,
      followed by neutrophil activation and directed migration to sites of infection
      through the basement membrane and interstitial extracellular matrix. Proteolytic
      enzymes and reactive oxygen species are produced and released by neutrophils in
      response to a variety of inflammatory stimuli. Although these mediators are
      important for host defense, they also promote tissue damage. Excessive neutrophil
      migration during the early stages of sepsis may lead to an exaggerated
      inflammatory response with associated tissue damage and subsequent organ
      dysfunction. On the other hand, dysregulation of migration and insufficient
      migratory response that occurs during the latter stages of severe sepsis
      contributes to neutrophils' inability to contain and control infection and
      impaired wound healing. This review discusses the major steps and associated
      molecules involved in the balance of neutrophil trafficking, the precise
      regulation of which during sepsis spells life or death for the host. 

PMID- 25567342
TI  - How uncomplicated total thyroidectomy could aggravate the laryngopharyngeal
      reflux disease?
AB  - Swallowing, voice disorders, throat discomfort and subjective neck discomfort are
      usually reported by patients with a known thyroid nodule and are correlated to
      nodular thyroid disease itself. Moreover, in endemic goitrous areas, total
      thyroidectomy (TT) is the most frequently performed surgical procedure. We are
      used to relate swallowing, voice and throat discomfort to the mechanical effects
      of nodular goiter or to thyroidectomy itself, but in both these cases the
      relationship between symptoms and the thyroid mass or its removal is not always
      clear or easily demonstrated. How can we explain the persistence of local neck
      symptoms after TT? And how can TT worsen the dysphagic or dysphonic disorders
      attributed to the goiter's effect over the surrounding structures? During these
      years, many articles have analyzed the relationship between the thyroid disease
      and the laryngopharyngeal reflux, finding more and more evidences of their
      consensuality, leading to important new management considerations and notable
      medico-legal implications; if the reason of local neck symptoms is not the
      thyroid disease, we have to study and specially cure the reflux disease, with
      specific test and drugs. Therefore, the aim of our study, relying on the
      published literature, was to investigate how, in demonstrated presence of reflux
      laryngopharyngitis in patients with nodular goiter and local neck symptoms before
      and after uncomplicated TT, the surgery could influence our anti-reflux mechanism
      analyzing the anatomical connection as well as the functional coordination; can
      we play a part in the post-operative persistence of swallowing and voice
      alterations and throat discomfort? 

PMID- 25567343
TI  - Re: Inner ear damage following electric current and lightning injury: a
      literature review.

PMID- 25567344
TI  - Impact of recombinant PTH on management of hypoparathyroidism: a systematic
      review.
AB  - The treatment of post-surgical hypoparathyroidism (following thyroid or
      parathyroid surgery) is challenging. Presently, this condition is treated with
      calcium and vitamin D supplements rather than replacing the missing parathyroid
      hormone. Not only is it challenging to maintain normocalcaemia, but concerns of
      hypercalciuria and ectopic calcification have also been raised using these
      supplements. There is an ongoing debate whether recombinant parathyroid hormone
      (rPTH), which as yet is unlicensed for treating hypoPTH, may offer a more
      physiological solution. The objective of the study was to assess the
      effectiveness and safety of rPTH in maintaining normocalcaemia and normocalcuria
      in hypoparathyroidism. This was a systematic review performed using independently
      developed search strategies including Medline, Embase, CINAHL, Cochrane, Zetoc,
      conference proceedings and a manual search until 15 July 2014. Data extraction
      was undertaken by one reviewer (YR). Studies were synthesised through narrative
      review with tabulation of results. Of 2,141 studies identified, only eleven
      studies fitted the inclusion criteria. These studies suggest that rPTH is useful
      in normalising serum calcium levels. Excretion of urinary calcium levels is
      reduced with PTH 1-34 but remained unchanged in a number of studies using PTH 1
      84. Recombinant PTH is well tolerated. The majority of studies included post
      surgical hypoparathyroidism with marked heterogeneity. Further prospective,
      larger, long-term trials are necessary to evaluate the long-term efficacy and
      adverse profile of rPTH, including head to head comparisons between PTH 1-34 and
      PTH 1-84.

PMID- 25567345
TI  - Laser surgery for Zenker's diverticulum: European combined study.
AB  - Surgical intervention is the gold standard of treatment for Zenker's
      diverticulum. The aim of this study was to examine the role of laser surgery in a
      large number of patients with this pathological entity. The data of 91
      consecutive patients treated due to Zenker's diverticulum with the aid of CO2
      laser in three institutions (Homburg/Saar and Marburg, Germany/Athens, Greece)
      during the last 10 years were retrospectively analyzed. Parameters examined were
      sex, age, preoperative symptoms, length of operation and complications, revision
      surgery necessity and degree of patient satisfaction. All patients had a minimum
      follow-up of one year. Dysphagia was the most common preoperative symptom (78 %).
      The most common minor complication was dental injury (6.6 %), but a serious
      complication in form of emphysema was observed in only two patients (2.2 %). A
      surgical revision was necessary in 8 (8.8 %) of the treated patients. The
      majority of treated patients was free of symptoms (86.8 %), or presented mild
      symptoms (9.9 %) one year after intervention, and only three patients (3.3 %)
      were dissatisfied. Our study shows that laser treatment of Zenker's diverticulum
      is an efficient operative technique associated with low complications rates and
      significant improvement of patients' symptoms in most of the examined cases.

PMID- 25567346
TI  - Factors impacting early cochlear implantation in Chinese children.
AB  - This study aimed to determine the factors that impact early cochlear implantation
      (CI) in Chinese children. The charts of 56 pediatric cochlear implant recipients
      were retrospectively reviewed. Parental interviews were conducted to collect
      information regarding the factors that potentially impact early CI in Chinese
      children. The mean age at CI was 40.98 months, and the median age was 24 months.
      Thirty patients received an implant before 24 months of age, and the other 26
      patients received the implant after 24 months of age. By univariate logistic
      regression analysis, newborn hearing screening (NHS), financial burden impacted
      early CI significantly (p < 0.05), while the multivariate analysis indicated that
      only NHS significantly influenced the early CI (p < 0.05). The following factors
      were associated with a moderately increased risk of late implantation: lack of
      NHS [odds ratio (OR) = 5.833], living in a rural community (OR = 2.714), and
      communication barriers (OR = 2.691). Living in a rural community, financial
      burden and communication barriers negatively impact the age at CI, whereas NHS
      positively influence the age at CI. Increased awareness of these factors could
      promote early CI and improve the quality of life of congenitally deaf children.

PMID- 25567347
TI  - Post-sialendoscopy ductoplasty by salivary duct stent placements.
AB  - With damage to a duct or papilla after sialendoscopy, a stent may be necessary to
      prevent re-stenosis and for maintaining the salivary duct open after complete
      sialendoscopy. However factors affecting outcomes and complications after stent
      placement remain unclear. This study aimed to report preliminary experiences in
      salivary duct stent placement after sialendoscopy. Data from 35 procedures in 33
      patients who received sialendoscopy with salivary duct stent placements at Mackay
      Memorial Hospital between October 2013 and June 2014 were recorded and compared
      for clinical data, as well as procedural techniques, findings, and outcomes. In
      the 35 stent placement procedures, the hypospadias silastic stent tubes were used
      in 27 and the Fr. 5 pediatric feeding tubes were used in the remaining eight.
      When the hypospadias silastic stent tubes were used for stenting, the stent
      obstruction and irritation rates were higher compared to those who used the Fr. 5
      pediatric feeding tube (100 vs. 0 % and 67 vs. 33 %, respectively). None of the
      stents secured by a 5-0 nylon suture were complicated by dislocation but when the
      stents were secured by 6-0 nylon sutures, the dislocation rate went as high as
      47.4 %. The duration needed for salivary duct stent placement might be
      potentially shortened to only 2 weeks. If a salivary duct stent is intended to be
      placed for a certain period before its scheduled removal, a suture strength
      equivalent or stronger than the 5-0 nylon suture should be considered for stent
      fixation.

PMID- 25567348
TI  - Tyrosine phosphatase-related islet antigen 2(256-760) autoantibodies, the only
      marker of islet autoimmunity that increases by increasing the degree of BMI in
      obese subjects with type 2 diabetes.
AB  - OBJECTIVE: Since patients with type 2 diabetes and positive for type 1 diabetes
      specific antibodies have wide variations in BMI, this study evaluated whether the
      frequency and pattern of islet autoantibody positivity is related to BMI.
      RESEARCH DESIGN AND METHODS: Clinical and biochemical characteristics and islet
      autoantibodies including GAD and protein tyrosine phosphatases islet antigen-2
      (IA-2)IC and IA-2(256-760) were evaluated in 1,850 patients with type 2 diabetes
      from the Non-Insulin Requiring Autoimmune Diabetes study cohort. BMI was
      evaluated in all patients, who were then subdivided in three groups according to
      BMI (<25, >=25 to <30, and >=30 kg/m(2)). RESULTS: Out of 1,850, 120 (6.5%)
      patients were positive for at least one of the following antibodies: GAD (4.1%),
      IA-2(256-760) (3.3%), or IA-2IC (1.1%). GAD and IA-2IC antibodies showed
      decreasing frequencies with increasing BMI (P < 0.0001 and 0.0006, respectively,
      for trend); in contrast, the frequency of IA-2(256-760) antibodies increased with
      increasing BMI (P = 0.005 for trend). Patients with type 2 diabetes positive for
      IA-2(256-760) alone showed a phenotype resembling classical obese type 2
      diabetes, with higher BMI, waist circumference, and uric acid (P < 0.005 for
      all), lower thyroid peroxidase antibodies, and lower progression to insulin
      requirement than GAD antibody-positive patients (P = 0.04 and P = 0.0005,
      respectively). CONCLUSIONS: The IA-2(256-760) antibody appears to represent an
      antibody marker that mainly identifies a clinical phenotype very similar to obese
      type 2 diabetes, suggesting a possible different pathogenetic mechanism.

PMID- 25567349
TI  - The newly synthesized anticancer drug HUHS1015 is useful for treatment of human
      gastric cancer.
AB  - Naftopidil is clinically for treatment of benign prostate hyperplasia, and
      emerging evidence has pointed to its anticancer effect. To obtain the anticancer
      drug with the potential greater than that of naftopidil, we have newly
      synthesized the naftopidil analogue HUHS1015. The present study investigated the
      mechanism underlying HUHS1015-induced apoptosis of human gastric cancer cells and
      assessed the possibility for clinical use as an innovative anticancer drug.
      HUHS1015 reduced cell viability for MKN28 human well-differentiated gastric
      adenocarcinoma cell line and MKN45 human poorly differentiated gastric
      adenocarcinoma cell line in a concentration (0.3-100 MUM)-dependent manner more
      effectively than cisplatin, a chemo-drug widely used. In the flow cytometry using
      propidium iodide (PI) and annexin V, HUHS1015 significantly increased the
      population of PI-positive and annexin V-negative cells, corresponding to primary
      necrosis and that of PI-positive and annexin V-positive cells, corresponding to
      late apoptosis/secondary necrosis, both in the two cell types. HUHS1015
      significantly activated caspase-3, caspase-4, and caspase-8 in MKN45 cells, while
      no obvious caspase activation was found in MKN28 cells. HUHS1015 upregulated
      expression of the tumor necrosis factor alpha (TNFalpha) mRNA and protein in
      MKN45 cells, allowing activation of caspase-8 through TNF receptor and the
      effector caspase-3. HUHS1015 clearly inhibited tumor growth in mice inoculated
      with MKN45 cells, with the survival rate higher than that for the anticancer
      drugs cisplatin, paclitaxel, and irinotecan. The results of the present study
      show that HUHS1015 induces caspase-independent and caspase-dependent apoptosis of
      MKN28 and MKN45 human gastric cancer cells, respectively, and effectively
      suppresses MKN45 cell proliferation. 

PMID- 25567350
TI  - A phase I, pharmacokinetic, and pharmacodynamic evaluation of the DNA
      methyltransferase inhibitor 5-fluoro-2'-deoxycytidine, administered with
      tetrahydrouridine.
AB  - PURPOSE: Inhibitors of DNA (cytosine-5)-methyltransferases (DNMT) are active
      antineoplastic agents. We conducted the first-in-human phase I trial of 5-fluoro
      2'-deoxycytidine (FdCyd), a DNMT inhibitor stable in aqueous solution, in
      patients with advanced solid tumors. Objectives were to establish the safety,
      maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of FdCyd +
      tetrahydrouridine (THU). METHODS: FdCyd + THU were administered by 3 h IV
      infusion on days 1-5 every 3 weeks, or days 1-5 and 8-12 every 4 weeks. FdCyd was
      administered IV with a fixed 350 mg/m(2)/day dose of THU to inhibit deamination
      of FdCyd. Pharmacokinetics of FdCyd, downstream metabolites and THU were assessed
      by LC-MS/MS. RBC gamma-globin expression was evaluated as a pharmacodynamics
      biomarker. RESULTS: Patients were enrolled on the 3-week schedule at doses up to
      80 mg/m(2)/day without dose-limiting toxicity (DLT) prior to transitioning to the
      4-week schedule, which resulted in an MTD of 134 mg/m(2)/day; one of six patients
      had a first-cycle DLT (grade 3 colitis). FdCyd >=40 mg/m(2)/day produced peak
      plasma concentrations >1 uM. Although there was inter-patient variability, gamma
      globin mRNA increased during the first two treatment cycles. One refractory
      breast cancer patient experienced a partial response (PR) of >90 % decrease in
      tumor size, lasting over a year. CONCLUSIONS: The MTD was established at 134
      mg/m(2) FdCyd + 350 mg/m(2) THU days 1-5 and 8-12 every 4 weeks. Based on
      toxicities observed over multiple cycles, good plasma exposures, and the
      sustained PR observed at 67 mg/m(2)/day, the phase II dose for our ongoing multi
      histology trial is 100 mg/m(2)/day FdCyd with 350 mg/m(2)/day THU.

PMID- 25567353
TI  - Incident angle-tuned, broadband, ultrahigh-sensitivity plasmonic antennas
      prepared from nanoparticles on imprinted mirrors.
AB  - We have used a direct imprint-in-metal method that is cheap and rapid to prepare
      incident angle-tuned, broadband, ultrahigh-sensitivity plasmonic antennas from
      nanoparticles (NPs) and imprinted metal mirrors. By changing the angle of
      incidence, the nanoparticle-imprinted mirror antennas (NIMAs) exhibited broadband
      electromagnetic enhancement from the visible to the near-infrared (NIR) regime,
      making them suitable for use as surface-enhanced Raman scattering (SERS)-active
      substrates. Unlike other SERS-active substrates that feature various structures
      with different periods or morphologies, the NIMAs achieved broadband
      electromagnetic enhancement from single configurations. The enhancement of the
      electric field intensity in the NIMAs originated from coupling between the
      localized surface plasmon resonance of the NPs and the periodic structure-excited
      surface plasmon resonance (SPR) of the imprinted mirror. Moreover, the coupling
      wavelengths could be modulated because the SPR wavelength was readily tuned by
      changing the angle of the incident light. Herein, we demonstrate that such NIMAs
      are robust substrates for visible and NIR surface-enhanced resonance Raman
      scattering under multiple laser lines (532, 633, and 785 nm) of excitation. In
      addition, we have found that NIMAs are ultrasensitive SERS-active substrates that
      can detect analytes (e.g., rhodamine 6G) at concentrations as low as 10(-15) M. 

PMID- 25567351
TI  - Human recombinant arginase I (Co)-PEG5000 [HuArgI (Co)-PEG5000]-induced arginine
      depletion is selectively cytotoxic to human glioblastoma cells.
AB  - In this study, we attempt to target Arginine auxotrophy in glioblastoma
      multiforme (GBM) cells using a pegylated recombinant human Arginase I cobalt
      [HuArgI (Co)-PEG5000]. We tested and characterized the activity of HuArgI (Co)
      PEG5000 on a panel of 9 GBM cell lines and on human fetal glial cells (SVG-p12).
      HuArgI (Co)-PEG5000 was cytotoxic to all GBM cells tested. SVG-p12 cells were not
      sensitive demonstrating the selective cytotoxicity of HuArgI (Co)-PEG5000-induced
      arginine deprivation. Addition of L-citrulline led to the rescue of 6 GBM cell
      lines but only at concentrations of 11.4 mM, reflecting the extent of arginine
      auxotrophy in GBM. The ability of L-citrulline to rescue cells was dependent on
      the expression of argininosuccinate synthetase-1 (ASS1) with the cells that were
      not rescued by L-citrulline being negative for ASS1 expression. Knocking-down
      ASS1 reversed the ability of L-citrulline to rescue GBM cells, further
      illustrating the dependence of arginine auxotrophy on ASS1 expression. Inhibition
      of autophagy increased cell sensitivity to HuArgI (Co)-PEG5000 indicating that,
      following arginine deprivation, autophagy plays a protective role in GBM cells.
      Analysis of the type of cell death revealed a lack of AnnexinV staining and
      caspase activation in HuArgI (Co)-PEG5000-treated cells, indicating that arginine
      deprivation induces caspase-independent, non-apoptotic cell death in GBM. We have
      shown that GBM cells are auxotrophic for arginine and can be selectively targeted
      using HuArgI (Co)-PEG5000-induced arginine depletion, thus demonstrating that L
      Arginine deprivation is a potent and selective potential treatment for GBM.

PMID- 25567352
TI  - Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2
      patients with growing vestibular schwannomas.
AB  - Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular
      schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor
      suppressor, was identified as a negative regulator of mammalian target of
      rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition
      delayed growth of NF2-schwannomas. We conducted a prospective single-institution
      open-label phase II study to evaluate the effects of everolimus in ten NF2
      patients with progressive VS. Drug activity was monitored every 3 months.
      Everolimus was administered orally for 12 months and, if the decrease in tumor
      volume was >20 % from baseline, treatment was continued for 12 additional months.
      Other patients stopped when completed 12 months of everolimus but were allowed to
      resume treatment when VS volume was >20 % during 1 year follow-up. Nine patients
      were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of
      everolimus, no reduction in volume >=20 % was observed. Four patients had
      progressive disease, and five patients had stable disease with a median annual
      growth rate decreasing from 67 %/year before treatment to 0.5 %/year during
      treatment. In these patients, tumor growth resumed within 3-6 months after
      treatment discontinuation. Everolimus was then reintroduced and VS decreased by a
      median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2
      months before treatment to > 12 months. Hearing was stable under treatment. The
      safety of everolimus was manageable. Although the primary endpoint was not
      reached, further studies are required to confirm the potential for stabilization
      of everolimus.

PMID- 25567354
TI  - DNA binding ability of histone-like protein HPhA is negatively affected by
      interaction with Pb2+.
AB  - The histone-like protein (HPhA) is highly homologous to the eukaryotic histones
      and has the ability to bind to the DNA molecules. In this study, we tested
      divalent metal ions Mg(2+), Ca(2+), Zn(2+), Pb(2+) for their effect on the
      recombinant HPhA (rHPhA)-DNA binding. We found that only Pb(2+) was able to
      reduce the formation of rHPhA-DNA complex using gel mobility shift assays.
      Equilibrium dialysis showed that Pb(2+) bound to rHPhA by a 2:1 ratio. The
      interaction of Pb(2+) and rHPhA was further studied by spectroscopic method
      including fluorescence, ultraviolet visible (UV-Vis) absorption, and circular
      dichroism (CD) spectroscopies. Fluorescent spectroscopy results suggested that
      Pb(2+) and rHPhA formed a complex that caused internal quenching of the
      fluorescence of the protein at the ground state, and the quenching is
      predominately static and mixed with dynamic quenching. UV-Vis absorption spectrum
      results showed Pb(2+) caused a slightly blue shift of the maximum absorption
      wavelength of rHPhA which indicated the reduction of the protein's
      hydrophobicity. The CD spectrum further indicated that a reduction of the alpha
      helix content of rHPhA occurred upon binding to Pb(2+). Synchronous fluorescence
      spectrometry analysis revealed that Pb(2+) was able to affect the polarity of the
      amino acids that near the Trp and Tyr residues. These results together showed
      that Pb(2+) interact with the recombinant rHPhA and this interaction negatively
      affect the ability of rHPhA to form complex with DNA molecules. 

PMID- 25567356
TI  - Effect of Duration of Ex Vivo Ischemia Time and Storage Period on RNA Quality in
      Biobanked Human Renal Cell Carcinoma Tissue.
AB  - BACKGROUND: RNA degradation is a major problem in tissue banking, and the effects
      of the ex vivo ischemia time, storage time, and transport conditions on RNA
      integrity and gene expression have not been well understood. METHODS: A total of
      100 fresh-frozen clear cell carcinoma tissues and matched normal tissues during
      five storage periods (<=6, 7-12, 13-18, 19-24, and 25-30 months) were chosen to
      detect RNA quality. At surgery, fresh kidney cancer tissues from five patients
      were cut into pieces and snap frozen. Additional fresh tissue pieces were (1)
      left at room temperature, (2) kept on ice, or (3) placed in normal saline before
      being snap frozen after 0.5, 1, 2, or 4 h. RNA integrity was determined by
      microchip electrophoresis, and gene expression was analyzed by real-time
      polymerase chain reaction. RESULTS: Altogether, 82 % of kidney cancer specimens
      banked using a standardized protocol yielded RNA with an RNA integrity number of
      >=7 (7.77 +/- 0.95, 7.87 +/- 0.37, 7.15 +/- 1.46, 8.10 +/- 0.64, and 7.11 +/-
      1.08 during the five storage periods, respectively). RNA remained intact after 4
      h on ice, whereas degradation was found in tissues left at room temperature or in
      saline. Expression of genes in certain functional pathways changed during storage
      under three conditions. CONCLUSIONS: More than 80 % of the banked kidney cancer
      biospecimens collected following a standardized protocol yielded high-quality
      RNA. Fresh human cancer tissue samples should be transported on ice before
      biobanking to avoid a major reduction in RNA quality. The presented data should
      be considered in attempts to further standardize tissue biospecimen collection
      and banking.

PMID- 25567355
TI  - Temperature, ozone, and mortality in urban and non-urban counties in the
      northeastern United States.
AB  - BACKGROUND: Most health effects studies of ozone and temperature have been
      performed in urban areas, due to the available monitoring data. We used observed
      and interpolated data to examine temperature, ozone, and mortality in 91 urban
      and non-urban counties. METHODS: Ozone measurements were extracted from the
      Environmental Protection Agency's Air Quality System. Meteorological data were
      supplied by the National Center for Atmospheric Research. Observed data were
      spatially interpolated to county centroids. Daily internal-cause mortality counts
      were obtained from the National Center for Health Statistics (1988-1999). A two
      stage Bayesian hierarchical model was used to estimate each county's increase in
      mortality risk from temperature and ozone. We examined county-level associations
      according to population density and compared urban (>=1,000 persons/mile(2)) to
      non-urban (<1,000 persons/mile(2)) counties. Finally, we examined county-level
      characteristics that could explain variation in associations by county. RESULTS:
      A 10 ppb increase in ozone was associated with a 0.45% increase in mortality (95%
      PI: 0.08, 0.83) in urban counties, while this same increase in ozone was
      associated with a 0.73% increase (95% PI: 0.19, 1.26) in non-urban counties. An
      increase in temperature from 70 degrees F to 90 degrees F (21.2 degrees C 32.2
      degrees C) was associated with a 8.88% increase in mortality (95% PI: 7.38,
      10.41) in urban counties and a 8.08% increase (95% PI: 6.16, 10.05) in non-urban
      counties. County characteristics, such as population density, percentage of
      families living in poverty, and percentage of elderly residents, partially
      explained the variation in county-level associations. CONCLUSIONS: While most
      prior studies of ozone and temperature have been performed in urban areas, the
      impacts in non-urban areas are significant, and, for ozone, potentially greater.
      The health risks of increasing temperature and air pollution brought on by
      climate change are not limited to urban areas.

PMID- 25567357
TI  - Is there a difference in total knee arthroplasty risk of revision in highly
      crosslinked versus conventional polyethylene?
AB  - BACKGROUND: Highly crosslinked polyethylene (HXLPE) was introduced to reduce wear
      and associated osteolysis in total knee arthroplasty (TKA). However, there is
      limited clinical evidence that HXLPE is more effective than conventional
      polyethylene (CPE) in TKA. QUESTIONS/PURPOSES: (1) Do primary TKAs with HXLPE
      tibial inserts have a lower risk of revision (all-cause, aseptic, and septic)
      than TKAs with CPE tibial inserts? (2) In NexGen TKA (Zimmer Inc, Warsaw, IN,
      USA) bearings, do HXLPE tibial inserts have a lower risk of revision (all-cause,
      aseptic, and septic) than CPE tibial inserts? (3) In Press-Fit Condylar TKA (PFC
      or PFC Sigma; DePuy Inc, Warsaw, IN, USA), do HXLPE tibial inserts have a lower
      risk of revision (all-cause, aseptic, and septic) than procedures performed with
      CPE tibial inserts? METHODS: The Kaiser Permanente Total Joint Replacement
      Registry was used to identify primary TKAs (N = 77,084) performed during the
      study period (April 2001 to December 2011) with cobalt-chromium alloy on CPE
      (CoCr-CPE) and CoCr-HXLPE bearings. The registry has 95% voluntary participation
      and less than 9% were loss to followup during the 10-year study period. A total
      of 60,841 (79%) had CoCr-CPE bearings, 11,048 (14%) had CoCr-HXLPE bearings, and
      5195 (7%) were unknown. Specific knee implant designs (NexGen, Zimmer and PFC
      Sigma, DePuy Inc) were also evaluated. These implants represented 41% (31,793)
      and 49% (37,457), respectively, of the 77,084 TKAs of known implant types
      registered during that period; implant selection was at the discretion of the
      attending surgeon. Descriptive statistics and marginal Cox regression models with
      propensity score adjustments were applied to compare risk of revision for CoCr
      CPE versus CoCr-HXLPE TKA bearings. RESULTS: At 5 years followup, cumulative
      incidence of revision for CoCr-CPE and CoCr-XLPE were 2.7% and 3.1%,
      respectively. Adjusted risks of all-cause (hazard ratio [HR], 1.05; 95%
      confidence interval [CI], 0.86-1.29; p = 0.620), aseptic (HR, 1.01; 95% CI, 0.77
      1.32; p = 0.954), and septic revision (HR, 1.11; 95% CI, 0.81-1.51; p = 0.519)
      did not differ in patients with CoCr-XLPE bearings compared with CoCr-CPE. Within
      TKAs with NexGen components, the adjusted risks of all-cause (HR, 1.14; 95% CI,
      0.86-1.51; p = 0.354), aseptic (HR, 1.14; 95% CI, 0.79-1.65; p = 0.493), and
      septic revision (HR, 1.14; 95% CI, 0.76-1.73; p = 518) were similar in patients
      with CoCr-XLPE compared with those with CoCr-CPE bearings. Finally, within the
      TKAs with PFC components, the adjusted risks of all-cause (HR, 0.80; 95% CI, 0.49
      1.30; p = 0.369), aseptic (HR, 0.62; 95% CI, 0.62-1.14; p = 0.123), and septic
      revision (HR, 0.97; 95% CI, 0.51-1.85; p = 0.929) were also similar in patients
      with CoCr-XLPE compared with those with CoCr-CPE bearings. CONCLUSIONS: In this
      large study, we did not find differences in risk of revision for CoCr-HXLPE
      compared with CoCr-CPE bearings at 5 years followup. In selecting HXLPE in TKA,
      clinicians should consider the increased cost and lack of available evidence of
      performance for greater than 10 years followup. Future studies are necessary to
      evaluate longitudinal outcomes of CoCr-HXLPE versus conventional TKA bearings.
      LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 25567358
TI  - CORR Insights((r)): survival, recurrence, and function after epiphyseal
      preservation and allograft reconstruction in osteosarcoma of the knee.

PMID- 25567359
TI  - Effects on channel properties and induction of cell death induced by c-terminal
      truncations of pannexin1 depend on domain length.
AB  - Pannexin1 (Panx1) is an integral membrane protein and known to form
      multifunctional hexameric channels. Recently, Panx1 was identified to be
      responsible for the release of ATP and UTP from apoptotic cells after site
      specific proteolysis by caspases 3/7. Cleavage at the carboxy-terminal (CT)
      position aa 376-379 irreversibly opens human Panx1 channels and leads to the
      release of the respective nucleotides resulting in recruitment of macrophages and
      in subsequent activation of the immunologic response. The fact that cleavage of
      the CT at this particular residues terminates in a permanently open channel
      raised the issue of functional relevance of the CT of Panx1 for regulating
      channel properties. To analyze the impact of the CT on channel gating, we
      generated 14 truncated versions of rat Panx1 cleaved at different positions in
      the C-terminus. This allowed elaboration of the influence of defined residues on
      channel formation, voltage-dependent gating, execution of cell mortality, and
      susceptibility to the Panx1 inhibitor carbenoxolone. We demonstrate that
      expression of Panx1 proteins, which were truncated to lengths between 370 and 393
      residues, induces differential effects after expression in Xenopus laevis oocytes
      as well as in Neuro2A cells with strongest impact downstream the caspase 3/7
      cleavage site. 

PMID- 25567360
TI  - Molecular mechanism of Mg-ATPase activity.
AB  - Mg-ATPase is very important in living organisms. To better understand the
      molecular mechanism of Mg-ATPase activity, we applied the method of kinetic
      analysis of multi-sited enzyme systems; this is a suitable approach used for
      kinetic investigation of multi-sited enzyme systems. The study of Mg-ATPase has
      demonstrated: (1) It is a multi-sited enzyme system whose functional unit is
      minimum a dimmer; (2) Its substrate is MgATP, while free ATP and Mg(2+) appear to
      be the enzyme modifiers with a dual effect; (3) The enzyme system for MgATP has
      at least three sites: i.e., the essential activator, full inhibitor, and partial
      effect modifiers sites; (4) Mg-ATPase carries out Mg(2+) transport through the
      1Mg(2+):1ATP stochiometry. Based on the results of these analyses, the kinetic
      scheme for Mg-ATPase has been developed. 

PMID- 25567361
TI  - Evolution of H9N2 influenza viruses isolated in Shandong Province.

PMID- 25567362
TI  - Robotic-assisted strictureplasty for Crohn's disease.

PMID- 25567364
TI  - La2O3-encapsulated SnO2 nanocrystallite-based photoanodes for enhanced DSSCs
      performance.
AB  - A SnO2 nanocrystallite-based photoanode was prepared using tin (iv) chloride and
      fructose via a one-pot hydrothermal method, and its structural and morphological
      properties were studied. Structural observations revealed tetragonal crystals of
      SnO2, and morphological studies confirmed the presence of spherical
      nanoparticulates. Furthermore, encapsulating the surface of the SnO2 photoanode
      (+N719 dye) with thin layers of La2O3 significantly improved the short-circuit
      current density, open-circuit voltage, fill factor and power conversion
      efficiency values from 8.30 to 13.70 mA cm(-2), 0.40 to 0.46 V, 49% to 48% and
      1.66% to 3.0%, respectively. The nearly two-fold improvement in energy conversion
      efficiency was attributed to: (a) increased dye molecules caused by the formation
      of strong co-ordination bonds between the dye molecules and the lanthanide, (b)
      enhanced photoelectron transfer rate between the dye molecules and SnO2
      conduction band, and (c) negative shift of SnO2 conduction band position in the
      presence of La2O3 (confirmed from the Mott-Schottky and Tafel measurements). 

PMID- 25567363
TI  - Alcohol consumption, drinking patterns, and ischemic heart disease: a narrative
      review of meta-analyses and a systematic review and meta-analysis of the impact
      of heavy drinking occasions on risk for moderate drinkers.
AB  - BACKGROUND: Alcohol consumption is a major global risk factor for mortality and
      morbidity. Much discussion has revolved around the diverse findings on the
      complex relationship between alcohol consumption and the leading cause of death
      and disability, ischemic heart disease (IHD). METHODS: We conducted a systematic
      search of the literature up to August 2014 using Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidelines to identify meta-analyses and
      observational studies examining the relationship between alcohol drinking,
      drinking patterns, and IHD risk, in comparison to lifetime abstainers. In a
      narrative review we have summarized the many meta-analyses published in the last
      10 years, discussing the role of confounding and experimental evidence. We also
      conducted meta-analyses examining episodic heavy drinking among on average
      moderate drinkers. RESULTS: The narrative review showed that the use of current
      abstainers as the reference group leads to systematic bias. With regard to
      average alcohol consumption in relation to lifetime abstainers, the relationship
      is clearly J-shaped, supported by short-term experimental evidence and similar
      associations within strata of potential confounders, except among smokers. Women
      experience slightly stronger beneficial associations and also a quicker upturn to
      a detrimental effect at lower levels of average alcohol consumption compared to
      men. There was no evidence that chronic or episodic heavy drinking confers a
      beneficial effect on IHD risk. People with alcohol use disorder have an elevated
      risk of IHD (1.5- to 2-fold). Results from our quantitative meta-analysis showed
      that drinkers with average intake of <30 g/day and no episodic heavy drinking had
      the lowest IHD risk (relative risk = 0.64, 95% confidence interval 0.53 to 0.71).
      Drinkers with episodic heavy drinking occasions had a risk similar to lifetime
      abstainers (relative risk = 1.12, 95% confidence interval 0.91 to 1.37).
      CONCLUSIONS: Epidemiological evidence for a beneficial effect of low alcohol
      consumption without heavy drinking episodes is strong, corroborated by
      experimental evidence. However, episodic and chronic heavy drinking do not
      provide any beneficial effect on IHD. Thus, average alcohol consumption is not
      sufficient to describe the risk relation between alcohol consumption and IHD.
      Alcohol policy should try to reduce heavy drinking patterns.

PMID- 25567366
TI  - Addressing the challenges of low clearance in drug research.
AB  - As a result of high-throughput ADME screening, early metabolite identification,
      and exploration of novel chemical entities, low-intrinsic-clearance compounds
      continue to increase in drug discovery portfolios. Currently available in vitro
      tools have limited resolution below a certain intrinsic clearance value, which
      can lead to overestimation of clearance and dose and underestimation of half
      life. Significant advances have been made in recent years and novel approaches
      have been developed to address the challenges of low clearance in drug discovery,
      such as the hepatocyte relay method, use of qNMR-based standards of
      biosynthesized drug metabolites to permit monitoring metabolite formation,
      coculture hepatocyte systems, and the time depending modeling approach. Future
      development in the field will enable faster, more precise, and lower cost
      profiling of the properties of low-clearance compounds for intrinsic clearance,
      metabolite identification, and reaction phenotyping. 

PMID- 25567365
TI  - beta2 adrenergic receptor activation governs cardiac repolarization and
      arrhythmogenesis in a guinea pig model of heart failure.
AB  - beta2-AR activation increases the risk of sudden cardiac death (SCD) in heart
      failure (HF) patients. Non-selective beta-AR blockers have greater benefits on
      survival than selective beta1-AR blockers in chronic HF patients, indicating that
      beta2-AR activation contributes to SCD in HF. This study investigated the role of
      beta2-AR activation on repolarization and ventricular arrhythmia (VA) in the
      experimental HF model. The guinea pig HF was induced by descending aortic
      banding. The effective refractoriness period (ERP), corrected QT (QTc) and the
      incidence of VA were examined using Langendorff and programmed electrical
      stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective
      beta2-AR agonist salbutamol significantly increased the incidence of VA,
      prolonged QTc and shortened ERP. These effects could be prevented by the
      selective beta2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced
      Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720)
      attenuated Ikr inhibition and APD prolongation induced by salbutamol. However,
      the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite
      effects. This study indicates that beta2-AR activation increases the incidence of
      VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition
      of Gi/PDE pathways. 

PMID- 25567367
TI  - Population pharmacokinetics and exposure-uric acid analyses after single and
      multiple doses of ABT-639, a calcium channel blocker, in healthy volunteers.
AB  - ABT-639 is a selective T-type calcium channel blocker with efficacy in a wide
      range of preclinical models of nociceptive and neuropathic pain. In the current
      first-in-human (FIH) study, the pharmacokinetics, tolerability, and safety of ABT
      639 after single- (up to 170 mg) and multiple doses (up to 160 mg BID) were
      evaluated in healthy volunteers in a randomized, double-blinded, placebo
      controlled manner. ABT-639 demonstrated acceptable safety and pharmacokinetic
      profiles in human. Results from assessment of the routine laboratory variables
      showed an unexpected statistically significant and clinically relevant decrease
      in blood uric acid with the increase in ABT-639 dose, which is possibly due to
      inhibition in URAT1 transporter. Pharmacokinetic/pharmacodynamic models were
      constructed to characterize the relationship between ABT-639 exposure and uric
      acid response. The final model was a mechanism-based indirect response
      pharmacodynamic model with the stimulation of uric acid elimination by ABT-639.
      The model estimated K in values in males and females were 10.2 and 7.13 MUmol/h,
      respectively. The model estimated K out was 0.033 1/h. ABT-639 concentration that
      can produce 50% stimulation in uric acid elimination was estimated to be 8,070
      ng/mL. Based on the final model, further simulations were conducted to predict
      the effect of ABT-639 on uric acid in gout patients. The simulation results
      indicated that, if the urate-lowering response to ABT-639 in gout patients is
      similar to that in healthy subjects, ABT-639 BID doses of 140 mg or higher would
      be expected to provide clinically meaningful lowering of blood uric acid levels
      below the 380 MUmol/L solubility limit of monosodium urate. 

PMID- 25567368
TI  - Rhodium(III)-catalyzed C7-position C-H alkenylation and alkynylation of
      indolines.
AB  - A Rh(III)-catalyzed regioselective C-H alkenylation and alkynylation of indolines
      is described. This protocol relies on the use of a removable pyridinyl directing
      group to access valuable C-7 functionalized indoline scaffolds with ample
      substrate scope and broad functional group tolerance.

PMID- 25567369
TI  - Genistein exerts neuroprotective effect on focal cerebral ischemia injury in
      rats.
AB  - Brain ischemia and treatment are one of the important topics in neurological
      science. Free oxygen radicals and inflammation formed after ischemia are accepted
      as the most important causes of damage. Currently, there are studies on many
      chemopreventive agents to prevent cerebral ischemia damage. Our aim is to
      research the preventive effect of the active ingredient in genistein, previously
      unstudied, on oxidative damage in cerebral ischemia. Rats were randomly divided
      into three groups: control group (no medication or surgical procedure), ischemia
      group, and artery ischemia+genistein group, sacrificed at 24 h after ischemia.
      The harvested brain tissue from the right hemisphere was investigated
      histopathologically and for tissue biochemistry. Superoxide dismutase and nuclear
      respiratory factor 1 values decreased after ischemia and they increased after
      genistein treatment, while increased malondialdehyde levels after ischemia
      reduced after treatment. Apoptosis-related cysteine peptidase caspase-3 and
      caspase-9 values increased after ischemia, but reduced after treatment. Our study
      revealed that genistein treatment in cerebral ischemia reduced oxidative stress
      and neuronal degeneration. We believe that genistein treatment may be an
      alternative treatment method.

PMID- 25567370
TI  - Reduced serum B7-H3 levels in patients with ankylosing spondylitis.
AB  - This study aimed to investigate molecule B7-H3 expression profiles of patients
      with ankylosing spondylitis (AS) and the clinical significance of B7-H3 in the
      pathogenesis of AS. Serum B7-H3 levels were measured by ELISA in patients with AS
      and healthy controls. The expression of B7-H3 protein and mRNA on CD14+ monocytes
      of peripheral blood mononuclear cells (PBMCs) and serum levels of T cell
      associated cytokines were also analyzed. The serum B7-H3 levels in AS patients
      were significantly lower than in healthy controls. The expression of B7-H3
      protein and mRNA on CD14+ monocytes of PBMCs and serum levels of TNF-alpha, IL-6,
      and IL-17A in AS patients were significantly higher than in controls. The reduced
      serum B7-H3 level was highly negatively correlated with AS Disease Activity Score
      (ASDAS), TNF-alpha, and IL-17A. Upregulated B7-H3 protein may play a role in the
      pathogenesis of AS by binding its receptor on T cells. 

PMID- 25567372
TI  - Singing can improve speech function in aphasics associated with intact right
      basal ganglia and preserve right temporal glucose metabolism: Implications for
      singing therapy indication.
AB  - Clinically, we know that some aphasic patients can sing well despite their speech
      disturbances. Herein, we report 10 patients with non-fluent aphasia, of which
      half of the patients improved their speech function after singing training. We
      studied ten patients with non-fluent aphasia complaining of difficulty finding
      words. All had lesions in the left basal ganglia or temporal lobe. They selected
      the melodies they knew well, but which they could not sing. We made a new lyric
      with a familiar melody using words they could not name. The singing training
      using these new lyrics was performed for 30 minutes once a week for 10 weeks.
      Before and after the training, their speech functions were assessed by language
      tests. At baseline, 6 of them received positron emission tomography to evaluate
      glucose metabolism. Five patients exhibited improvements after intervention; all
      but one exhibited intact right basal ganglia and left temporal lobes, but all
      exhibited left basal ganglia lesions. Among them, three subjects exhibited
      preserved glucose metabolism in the right temporal lobe. We considered that
      patients who exhibit intact right basal ganglia and left temporal lobes, together
      with preserved right hemispheric glucose metabolism, might be an indication of
      the effectiveness of singing therapy. 

PMID- 25567371
TI  - Inhibitory Effects of Polydatin on Lipopolysaccharide-Stimulated RAW 264.7 Cells.
AB  - The purpose of this study was to evaluate the effects of polydatin (PD) on
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions
      at protein and transcriptional levels, as well as the production of prostaglandin
      E2 (PGE2) and nitric oxide (NO) in lipopolysaccharide (LPS)-induced macrophage
      RAW 264.7 cells. To elucidate the underlying mechanism responsible for these
      symptoms, we investigated the phosphorylation of mitogen-activated protein kinase
      (MAPK) pathway and nuclear factor-kappaB (NF-kappaB) expression. NO was analyzed
      with the Griess method. PGE2 was measured by enzyme-linked immunosorbent assay
      (ELISA). iNOS and COX-2 messenger RNA (mRNA) were identified by qPCR assay. iNOS,
      COX-2, NF-kappaB, extracellular signal-regulated kinase (ERK), c-Jun N-terminal
      kinase (JNK) and p38 protein expressions were detected with Western blot. The
      results revealed that PD effectively inhibited NO and PGE2 production, and it is
      not surprising that PD reduced iNOS and COX-2 expression at protein and
      transcriptional levels. Additionally, PD significantly ameliorated the activation
      of NF-kappaB and the phosphorylation of MAPKs in LPS-induced RAW 264.7
      macrophages. These findings suggested that PD exerted potent anti-inflammatory
      activity in macrophages. 

PMID- 25567373
TI  - Hierarchical nanostructures of gamma-TaON flowers for enhanced visible light
      driven photocatalytic activities.
AB  - Hierarchical nanostructures of single phase gamma-TaON flowers have been
      successfully synthesized using a simple wet-chemical route in addition to
      subsequent thermal nitridation. These flower-like particles exhibit an obvious
      improvement in visible-light-driven photocatalytic activity. 

PMID- 25567375
TI  - The Barrie Jones Lecture-Eye care for the neglected population: challenges and
      solutions.
AB  - Globally, pockets of 'neglected populations' do not have access to basic health
      care services and carry a much greater risk of blindness and visual impairment.
      While large-scale public health approaches to control blindness due to vitamin A
      deficiency, onchocerciasis, and trachoma are successful, other causes of
      blindness still take a heavy toll in the population. High-quality comprehensive
      eye care that is equitable is the approach that needs wide-scale application to
      alleviate this inequity. L V Prasad Eye Institute of India developed a multi-tier
      pyramidal model of eye care delivery that encompasses all levels from primary to
      advanced tertiary (quaternary). This has demonstrated the feasibility of
      'Universal Eye Health Coverage' covering promotive, preventive, corrective, and
      rehabilitative aspects of eye care. Using human resources with competency-based
      training, effective and cost-effective care could be provided to many
      disadvantaged people. 

PMID- 25567374
TI  - Chromodomain helicase DNA-binding proteins in stem cells and human developmental
      diseases.
AB  - Dynamic regulation of gene expression is vital for proper cellular development
      and maintenance of differentiated states. Over the past 20 years, chromatin
      remodeling and epigenetic modifications of histones have emerged as key
      controllers of rapid reversible changes in gene expression. Mutations in genes
      encoding enzymes that modify chromatin have also been identified in a variety of
      human neurodevelopmental disorders, ranging from isolated intellectual disability
      and autism spectrum disorder to multiple congenital anomaly conditions that
      affect major organ systems and cause severe morbidity and mortality. In this
      study, we review recent evidence that chromodomain helicase DNA-binding (CHD)
      proteins regulate stem cell proliferation, fate, and differentiation in a wide
      variety of tissues and organs. We also highlight known roles of CHD proteins in
      human developmental diseases and present current unanswered questions about the
      pleiotropic effects of CHD protein complexes, their genetic targets, nucleosome
      sliding functions, and enzymatic effects in cells and tissues. 

PMID- 25567378
TI  - What's new in perioperative renal dysfunction?

PMID- 25567376
TI  - The 2014 Bowman Lecture-Bowman's and Bruch's: a tale of two membranes during the
      laser revolution.
AB  - To describe the historical evolution of the role of lasers in effecting
      therapeutic changes in the four acellular membranes of the eye. Over the past 50
      years, iterative developments have been instituted in lasers used for various
      forms of eye surgery predominately on the basis of data generated in early
      experiments in the 1960s to determine thresholds for damage and their
      incorporation in codes of practice for laser safety. The evolutionary steps are
      described. Excimer laser technology resulted in the generation of the new field
      of laser refractive surgery with over 40 million individuals now having undergone
      procedures such as photorefractive keratectomy and LASIK. Developments in lasers
      used for various forms of retinal surgery have undergone changes involving
      shorter and shorter pulse durations together with changes in beam energy
      distribution with implications for potential intervention in AMD
      prophylactically. Lasers have made a major impact on surgical treatment on all
      four acellular membranes of the eye but particularly Bowman's membrane in
      refractive surgery, where it has been demonstrated that it can be removed without
      significant consequences for eye health or vision. 

PMID- 25567379
TI  - Applying mean systemic filling pressure to assess the response to fluid boluses
      in cardiac post-surgical patients.
AB  - PURPOSE: To evaluate an analogue of mean systemic filling pressure (P(msa)) and
      derived variables to quantitatively assess the effectiveness of volume expansion
      in increasing cardiac output. METHODS: Sixty-one cardiac post-surgical patients
      were studied and 107 fluid boluses were captured. Cardiac output, mean arterial
      pressure and right atrial pressure were recorded with P msa before and after a
      bolus fluid. An increase in cardiac output greater than 10 % following a fluid
      bolus defined a patient as a responder. Cardiac power (i.e. the product of
      arterial pressure and cardiac output) and P(msa) to right atrial pressure
      gradient (i.e. the driving pressure for venous return and hence cardiac output)
      were evaluated to assess the efficiency of volume expansion to increase cardiac
      output. Cardiac power relative to P(msa) (CP(vol)), its dynamic changes and the
      dynamic changes in P msa-right atrial pressure gradient relative to the P(msa)
      change (E(vol)) were investigated. RESULTS: CP(vol) was lower and E(vol) was
      higher in responders vs. non-responders. Furthermore, in patients receiving a
      second fluid bolus, E(vol) correlated with the degree of increase in cardiac
      output. Multivariate regression analysis identified both CP(vol) and E(vol) as
      independent variables associated with volume responsiveness. CONCLUSIONS: Using
      an algorithm to derive a mean systemic filling pressure analogue, cardiac power
      and dynamic measures of the venous return pressure gradient relative to the mean
      systemic filling pressure provided an assessment of the efficiency of volume
      expansion in post-surgical cardiac patients.

PMID- 25567380
TI  - Understanding ARDS-associated fibroproliferation.

PMID- 25567381
TI  - Orthopnea with platydeoxia secondary to prominent Eustachian valve.

PMID- 25567382
TI  - Does the Berlin definition for acute respiratory distress syndrome predict the
      presence of diffuse alveolar damage?

PMID- 25567383
TI  - Acute kidney injury according to KDIGO stages and maternal mortality in the
      intensive care unit.

PMID- 25567384
TI  - Ultrasound-guided central venous access: what's new?

PMID- 25567385
TI  - [Late diagnosis of HIV infection].

PMID- 25567386
TI  - [Allergology in the public health service of the Community of Madrid: current
      situation and opportunities in the XXI century public health system].
AB  - The high prevalence of allergic diseases and the use of more complex diagnostic
      techniques and therapeutic options require allergists to be highly trained
      professionals and health-care organizations to be knowledgeable about available
      structural and human resources. Updated information is lacking in Spain, and
      current activity indicators do not reflect complexity. The present article
      analyzes the situation of allergology in Madrid and proposes improvements where
      necessary. The heads of the allergy departments of public hospitals in Madrid
      voluntarily completed a purpose-designed survey. Data on care activity (2010) and
      on teaching and research activity (2009-2010) were provided. A SWOT analysis was
      performed, and strategic lines and proposals for improvement were designed. One
      hundred and seventeen allergists (41% with a PhD) worked in 24 hospitals with an
      allergology department (4.6 physicians/center; <=3 in 10 hospitals). All the
      institutions had an outpatient clinic (4,000 first consultations/hospital/year,
      36% high-resolution rate; 6200 successive visits/hospital/year) performing
      complex diagnostic and therapeutic procedures, most of which were not taken into
      account by activity indicators. Two hospitals had their own hospitalization
      facilities and 10 were accredited teaching hospitals (2.78 medical
      residents/year). The survey revealed that, twice yearly, a typical allergology
      service participated in 4 research projects, 2 clinical trials, 16 publications
      and 17 communications at scientific meetings, with notable differences between
      hospitals. Allergists in Madrid are well prepared. The allergology care structure
      is adequate, although possibly insufficient. Quality and efficiency can be
      improved with new tools for recording activity and by increasing coordination and
      taking advantage of new technologies and geographical proximity. 

PMID- 25567387
TI  - [Late diagnosis of HIV infection: missed diagnostic opportunities].
AB  - BACKGROUND: To analyse the percentage of patients with a late diagnosis (LD) of
      HIV infection, their risk factors and the missed opportunities for an earlier
      diagnosis. METHODS: One hundred and sixty-five patients diagnosed with HIV
      infection in Navarre between 2009 and 2113 were included. Logistic regression was
      used to study the factors associated with LD (CD4 < 350 cells/mm3 or AIDS
      defining disease at diagnosis). The presence of risk factors and clinical
      indicators of possible HIV infection in the 5 years preceding the diagnosis were
      analyzed. RESULTS: The global prevalence of LD was 55% (90/165). This percentage
      was greater in immigrant patients than in Spanish patients, and in those without
      previous serology tests. An interaction was observed between the age and origin
      of patients. In Spaniards the risk of LD rose with age after 40 years (OR: 3.72;
      95%CI: 1.52-9.12) but this did not occur in immigrant patients. Of the 132
      patients who had received medical care in the years prior to diagnosis, 20 (15%)
      had classical risk factors recorded in their history, 14 (11%) proceeded from
      regions with a high prevalence of HIV, and 46 (35%) had presented clinical
      indicators (only 24 of them 1 year before diagnosis) without a serology test
      being realized. CONCLUSIONS: In spite of multiple contacts with our health
      system, over half of the new cases of HIV infection are diagnosed late. Greater
      attention to clinical signs is needed and, above all, a better evaluation of the
      risk in asymptomatic patients.

PMID- 25567388
TI  - [Treatment of prostate cancer according to life expectancy, comorbidity and
      clinical practice guidelines].
AB  - BACKGROUND: To describe the treatment of prostate cancer patients according to
      life expectancy, risk and comorbidity, to examine the degree to which Clinical
      Practice Guidelines (CPG) are followed, and to register secondary effects after
      one year. METHODS: Retrospective study of patients diagnosed with prostate cancer
      in a hospital in 2011. Socio-demographic variables, as well as comorbidity
      (Charlson index), tumor characteristics, treatments and secondary effects were
      collected. A bivariate analysis was performed using the Chi square test. RESULTS:
      One hundred and fourteen patients were identified. Life expectancy was higher
      than 10 years in 92.1%; 50% had low comorbidity, 36% medium and 14% high. Surgery
      was performed in 56.2%, more often in patients with intermediate-risk and low
      comorbidity; radiotherapy in 13.2%, more often in patients with high-risk and low
      comorbidity; hormonal therapy in 21.9%, more often in patients with medium
      comorbidity, and deferred treatment in 12.3%. CPG recommendations were not
      followed in 38.6%, especially in high-risk patients, 58.1%. Regarding adverse
      effects, 70% of patients treated with surgery presented urinary incontinence, and
      48.3% erectile dysfunction. On the other hand, 17.15% of patients treated with
      hormonal therapy presented a cardiovascular disease, and 32.5% worsening of a
      cardiovascular risk factor. CONCLUSIONS: Treatment of prostate cancer takes into
      account risk and comorbidity, but there could be improvement in following CPG
      guidelines, especially in elderly patients. It is advisable to develop preventive
      strategies to avoid cardiovascular effects in patients with hormonal therapy.

PMID- 25567389
TI  - Parity implications for anthropometrical variables, lifestyle behaviors and
      dietary habits in pregnant women.
AB  - BACKGROUND: Maintaining an adequate health status and appropriate lifestyles
      during pregnancy is of great importance to prevent adverse outcomes for both
      mother and baby. The present study aimed to assess the nutritional status, socio
      demographic features, lifestyle behaviors and dietary habits of pregnant women in
      Spain, and to identify the influence of parity on these profiles. METHODS: This
      cross-sectional study included pregnant women from regions all over Spain. The
      information was collected through a 40 item questionnaire, previously validated
      by community health professionals. RESULTS: The 5,087 pregnant women analyzed had
      an average age of 31.9 years with an adequate nutritional status. The
      distribution of the sample was 56% nulliparous and 44% multiparous. The
      nulliparous reported a better self-perceived health status and nutritional
      balance, and a lower incidence of gestational diabetes mellitus. However, the
      multiparous showed healthier lifestyle habits (lower rates of smoking and alcohol
      consumption) and more physically active patterns. Regarding diet, nulliparous
      pregnant women consumed more dairy products, fresh fruit and nuts, and less
      bread, rice/pasta/potatoes, meat, sausage and buns/pastries than multiparous
      pregnant women. CONCLUSIONS: Differences between analyzed patterns were observed
      in anthropometrical variables, lifestyle behaviors and dietary habits, which may
      require different nutritional messages to nulliparous as compared to multiparous
      from a public health point of view.

PMID- 25567390
TI  - [Safety and efficacy of a prothrombin complex concentrate in patients with
      coagulopathy and hemorrhage].
AB  - BACKGROUND: Prothrombin complex concentrates (PCC) are approved for urgent
      reversal of vitamin K antagonists (VKA). Recently, PCC have been used in the
      management of massive bleeding-associated coagulopathy. The present work
      evaluates safety and efficacy of PCC in a case series of both VKA reversal and
      massive bleeding. METHODS: Retrospective review of cases treated with CCP
      (January 2010 to February 2013). Safety endpoints were infusion reactions and
      incidence of thromboembolic events. Efficacy endpoints were: 1) VKA reversal
      efficacy and 2) Massive bleeding coagulopathy reversal and 24h mortality.
      RESULTS: Thirty-one patients were included (22 male), median age 61 years (range
      30-86). No infusion reactions were detected, and only 1 thrombotic episode was
      observed. VKA reversal was effective in 100% of patients (6/6), all of them with
      complete reversal of INR value. In massive bleeding, 24-hour survival was 64%
      (16/25). Invasive hemostatic procedures were required in 28% of patients (7/25).
      CCP use was correlated with bleeding control in 44% of cases (11/25), and also
      significantly associated with survival (p=0.01). CONCLUSION: CCP are safe and
      effective for the novel indication of adjuvant treatment in massive bleeding
      patients, as well as for traditional urgent reversal of VKA.

PMID- 25567391
TI  - [Evaluation of health information about the influenza vaccine on internet].
AB  - BACKGROUND: The quality of health information on internet is a question of
      concern to governments and users. Our aim was to determine the extent to which
      information about the influenza vaccine adheres to the gold standard set by the
      Spanish Health Ministry. METHODS: Between June and July 2014 information on
      indications, adverse effects and counter-indications of the vaccine was evaluated
      to see if it adhered to this gold standard. This information was obtained through
      Google, using terms provided by medical students. A univariate analysis was
      performed, where the variable result was getting information that adhered
      correctly to the standard, and explanatory variables were the type of origin of
      the information and its country. RESULTS: Using the terms provided by 104
      students, we obtained 134 different web links. Adhesion reached 65.7% (88/134)
      with respect to indication in health workers (HW). Nineteen point four percent
      provided incorrect information on indication in pregnant women. There was
      significantly better adherence in the information from official public health
      bodies (indication in HW (OR: 2.6), pregnant women (OR: 5.4) and immunodepressed
      patients (OR: 2.2)). Adherence of information on Spanish web links was worse
      (indication in pregnancy (OR: 0.3) and counter-indication if allergic to eggs
      (OR: 0.5). CONCLUSIONS: Adhesion was improvable. It's necessary to promote that
      internet users use official public health bodies websites when they search
      information regarding influenza vaccine on internet.

PMID- 25567330
TI  - Boosted lopinavir- versus boosted atazanavir-containing regimens and immunologic,
      virologic, and clinical outcomes: a prospective study of HIV-infected individuals
      in high-income countries.
AB  - BACKGROUND: Current clinical guidelines consider regimens consisting of either
      ritonavir-boosted atazanavir or ritonavir-boosted lopinavir and a nucleoside
      reverse transcriptase inhibitor (NRTI) backbone among their recommended and
      alternative first-line antiretroviral regimens. However, these guidelines are
      based on limited evidence from randomized clinical trials and clinical
      experience. METHODS: We compared these regimens with respect to clinical,
      immunologic, and virologic outcomes using data from prospective studies of human
      immunodeficiency virus (HIV)-infected individuals in Europe and the United States
      in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS
      free individuals were followed from the time they started a lopinavir or an
      atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir
      vs lopinavir regimens on each of the outcomes. RESULTS: A total of 6668
      individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses
      or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157
      AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios
      for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53
      .91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and
      0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month
      increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/uL higher in the
      atazanavir group. Estimates differed by NRTI backbone. CONCLUSIONS: Our estimates
      are consistent with a lower mortality, a lower incidence of AIDS-defining
      illness, a greater 12-month increase in CD4 cell count, and a smaller risk of
      virologic failure at 12 months for atazanavir compared with lopinavir regimens.

PMID- 25567392
TI  - [Efficacy of training pelvic floor musculature in female urinary incontinence].
AB  - Urinary incontinence "as the involuntary loss of urine, which conditions a social
      and hygienic problem" is defined. There are a variety of techniques for the
      treatment of urinary incontinence. Our goal is to determine the clinical
      effectiveness of different methods used to train the musculature of the pelvic
      floor as treatment for female urinary incontinence, both stress and mixed, and
      its contribution to improving the quality of life of these patients. For this
      purpose we performed a systematic review of controlled clinical trials. After
      analysing the results, we conclude that the treatment of stress or mixed urinary
      incontinence through training exercises for the musculature of the pelvic floor
      contributes positively to improving symptoms and strengthening the muscles of the
      pelvic floor and to the quality of life of affected patients. 

PMID- 25567394
TI  - [Analgesic techniques for labour: alternatives in case of epidural failure].
AB  - Epidural analgesia is now the method of choice for the treatment of pain in
      labour and delivery. However, this technique may fail and provide inadequate or
      null alleviation to the mother. This paper reviews the risk factors, possible
      causes and possible therapeutic alternatives to inadequate analgesia, whether
      pharmacological therapies (neuroaxial, peripheral blocks or analgesic
      administration via intravenous or inhalational routes) or non-pharmacological
      ones (relaxation techniques, psychological or mechanical). In all possible cases
      the efficacy and indications of alternative therapies based on the published
      literature are reviewed, especially from the point of view of evidence-based
      medicine. The need is underscored of a multifactorial therapeutic approach to the
      pregnant woman, not just restricting ourselves to eliminating the pain of
      childbirth. 

PMID- 25567393
TI  - [The challenges of health promotion in a multicultural society: a narrative
      review].
AB  - Nowadays multicultural reality leads health professionals to interact in their
      daily work with individuals and families from diverse cultures. The interaction
      between a person or family and a health professional from a different culture is
      called "cultural encounter". These encounters involve difficulties, complications
      and barriers, which health professionals will have to face in order to provide
      good care and promote healthy lifestyles. This narrative review shows that the
      difficulties are related to cultural and linguistic factors, health literacy,
      disadvantages in socio-economic status and the prejudices and stereotypes of
      healthcare professionals. Different strategies are described in the literature
      that could help health professionals to overcome these difficulties, namely: the
      development of culturally appropriate programmes; appropriate pedagogy and
      resources, and the use of culturally and linguistically sensitive materials; the
      use of interpreters and the organization of courses to learn the most widely
      spoken language. In addition to these strategies, the need is underscored for a
      change of approach in which the objective should be training health professionals
      to achieve so-called "cultural competence". Training in cultural competence would
      encourage professionals to offer tailored care plans, taking into account the
      cultural values, beliefs and practices of any person or family, and would help
      them to avoid stereotypes and prejudices. 

PMID- 25567396
TI  - PET/CT imaging for metastatic choroidal melanoma.

PMID- 25567395
TI  - Importance of genetics in acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) comprises a biologically and clinically
      heterogeneous group of aggressive disorders that occur as a consequence of a wide
      variety of genetic and epigenetic abnormalities in hematopoietic progenitors.
      Despite significant advances in the understanding of the biology of AML, most
      patients will die from relapsed disease. Whole-genome studies have identified
      novel recurrent gene mutations with prognostic impact in AML; furthermore, it is
      likely that in the near future genome-wide sequencing will become a routine for
      newly diagnosed patients with AML. Therefore, future clinical trials should aim
      to identify genetically defined high-risk patients, and further research is
      necessary to identify effective agents and develop new individualized therapeutic
      strategies for the treatment of this deadly disease.

PMID- 25567398
TI  - [Oxidative stress markers in the diagnosis of rheumatoid arthritis].

PMID- 25567397
TI  - [The use of prescription tools would avoid medication poisoning in the elderly].

PMID- 25567400
TI  - [Persistent fever syndrome secondary to brain abscesses: a rare complication of
      the meningococcemia].
AB  - Meningococcal disease is caused by hematogenous spreading of Neisseria
      meningitidis. Meningococcal sepsis occurs in around 20% of cases of meningococcal
      disease, meningitis in 50% and, to a lesser extent, other conditions such as
      pneumonia, arthritis, urethritis, conjunctivitis or pericarditis. Brain abscesses
      are a rare complication. 

PMID- 25567399
TI  - [Chylous fistula following lymphadenectomy in breast cancer].
AB  - Axillary lymph node dissection remains an integral part of surgical treatment in
      patients with invasive breast cancer and axillary lymph node metastases. Chylous
      leakage after axillary lymph node dissection is infrequent. We report the case of
      a patient with an advanced local breast cancer that was subsidiary to surgery
      treatment after neoadjuvant chemotherapy. She had a postoperative chylous
      leakage; it was successfully treated conservatively in the postoperative course.
      Chylous leakage an infrequent complication alters axillary lymph node dissection,
      which has a conservative management in most published studies. 

PMID- 25567401
TI  - [Clindamycin as adjuvant therapy in Staphilococcal skin scalded syndrome].
AB  - Staphylococcal scalded skin syndrome (SSSS) is a dermatologic disease caused by
      exotoxins produced by Staphylococcus aureus. The disease presents as a painful
      cutaneous rash that culminates with the detachment of the superficial dermis. The
      usual treatment is antibiotics with beta-lactamase resistant penicillin. We
      report the case of a patient who presented with SSSS with initial torpid
      evolution despite antibiotic treatment and after the introduction of clindamycin
      IV experienced a very significant improvement. Concerns about the increase of
      methicillin resistant Staphylococcus aureus (MRSA) and the pathophysiology of
      this disease make bacteriostatic spectrum antistaphylococcal antibiotics, such as
      clindamycin, strong candidates for consideration as a first-line therapeutic
      arsenal for the treatment of SSSS. 

PMID- 25567402
TI  - System matrix analysis for sparse-view iterative image reconstruction in X-ray
      CT.
AB  - Iterative image reconstruction (IIR) with sparsity-exploiting methods, such as
      total variation (TV) minimization, used for investigations in compressive sensing
      (CS) claim potentially large reductions in sampling requirements. Quantifying
      this claim for computed tomography (CT) is non-trivial, as both the singularity
      of undersampled reconstruction and the sufficient view number for sparse-view
      reconstruction are ill-defined. In this paper, the singular value decomposition
      method is used to study the condition number and singularity of the system matrix
      and the regularized matrix. An estimation method of the empirical lower bound is
      proposed, which is helpful for estimating the number of projection views required
      for exact reconstruction. Simulation studies show that the singularity of the
      system matrices for different projection views is effectively reduced by
      regularization. Computing the condition number of a regularized matrix is
      necessary to provide a reference for evaluating the singularity and recovery
      potential of reconstruction algorithms using regularization. The empirical lower
      bound is helpful for estimating the projections view number with a sparse
      reconstruction algorithm. 

PMID- 25567403
TI  - Deformation vector fields (DVF)-driven image reconstruction for 4D-CBCT.
AB  - BACKGROUND: High quality 4D-CBCT can be obtained by deforming a planning CT
      (pCT), where the deformation vector fields (DVF) are estimated by matching the
      forward projections of pCT and 4D-CBCT projections. The matching metric used in
      the previous study is the sum of squared intensity differences (SSID). The
      scatter signal level in CBCT projections is much higher than pCT, the SSID metric
      may not lead to optimal DVF. OBJECTIVE: To improve the DVF estimation accuracy,
      we develop a new matching metric that is less sensitive to the intensity level
      difference caused by the scatter signal. METHODS: The negative logarithm of
      correlation coefficient (NLCC) is used as the matching metric. A non-linear
      conjugate gradient optimization algorithm is used to estimate the DVF. A 4D NCAT
      phantom and an anthropomorphic thoracic phantom were used to evaluate the NLCC
      based algorithm. RESULTS: In the NCAT phantom study, the relative reconstruction
      error is reduced from 18.0% in SSID to 14.13% in NLCC. In the thoracic phantom
      study, the root mean square error of the tumor motion is reduced from 1.16 mm in
      SSID to 0.43 mm in NLCC. CONCLUSION: NLCC metric can improve the image
      reconstruction and motion estimation accuracy of DVF-driven image reconstruction
      for 4D-CBCT.

PMID- 25567404
TI  - Left ventricle segmentation in dynamic cardiac CT using random walks method.
AB  - PURPOSE: Segmentation of the left ventricle (LV) in cardiac CT (CCT) images is
      difficult due to the intensity heterogeneity arising from accumulation of
      contrast agent in papillary muscle and trabeculae carneae. In this study, we
      demonstrated the random walks method for LV segmentation in CCT through cardiac
      phases. METHODS: 63 CCT data sets from 7 patients with 9 cardiac phases were
      included in this study. All cardiac CT examinations were performed with GE 64
      detector CT scanner with ECG gating. In each patient, 60-80 ml iohexol was
      injected at a flow rate of 5 ml/sec followed by 60 ml normal saline solution.
      Random walks (RW) based on probability of labels was used for LV segmentation.
      The LV delineations generated by the experienced physician (MD), conventional
      image-based method (IB), and RW were compared. RESULTS: In general the contours
      segment the LV closely by RW and MD, but the discrepancies in papillary muscle
      and trabeculae carneae were observed while using the IB method. CONCLUSION: We
      showed the RW method potentially improved LV segmentation as compared to the
      volume by conventional IB method. In this study, we demonstrated the clinical
      feasibility of LV volume segmentation using random walks algorithm.

PMID- 25567405
TI  - Maximum intensity projection using bidirectional compositing with block skipping.
AB  - BACKGROUND: Maximum intensity projection (MIP) is a volume rendering technique
      that determines the pixel intensity as the maximum of all values sampled along
      the viewing direction. MIP has been successfully applied to diagnose bone
      fractures in computed tomography (CT) and the stenosis of vascular structures in
      magnetic resonance angiography (MRA). However, MIP has a major drawback in that
      the depth and occlusion information cannot be perceived in the output images. The
      most universal way to alleviate this problem is to occasionally change the
      viewpoint for depth perception. To support this function in real time, MIP should
      be performed at an interactive frame rate. OBJECTIVE: We develop an efficient
      rendering algorithm for MIP so that MIP is performed at an interactive frame rate
      without a loss of image quality. METHODS: The proposed method predicts the
      position of the maximum intensity for each ray using blockwise maximum bounds,
      after which it performs bidirectional compositing toward both ends of the ray
      from this predicted position. During the compositing process, block skipping is
      used as an acceleration method. RESULTS: The proposed method outperformed the
      block skipping method using the sequential compositing with a speed-up factor of
      2.2 ~ 2.8 depending on the data set without any degradation of the image quality.
      CONCLUSION: We proposed an efficient rendering technique for MIP. Our method was
      superior to the conventional block skipping method with respect to the rendering
      speed and degree of performance consistency.

PMID- 25567406
TI  - Clinical values of of gemstone spectral CT in diagnosing thyroid disease.
AB  - OBJECTIVE: To quantitatively evaluate the diagnostic value of gemstone spectral
      CT in thyroid disease. PATIENTS AND METHODS: A total of 123 patients with thyroid
      diseases were enrolled in the retrospective study. All the patients underwent
      spectral CT scan, and 39 of them underwent dual-phase enhanced scan. Iodine
      concentration (IC) and normalized IC (NIC) were compared between benign and
      malignant nodules. The optimal threshold to predict malignancy was obtained by
      receiver operating characteristic curve (ROC). Multivariate ROC analysis was
      performed to evaluate the efficacy of combining the IC (NIC) and conventional
      morphological characteristics. RESULTS: Ten diffuse diseases and 113 nodular
      diseases were confirmed by clinical laboratory examination and histopathology. In
      total, 122 nodules (87 benign and 35 malignant) were detected, 41 nodules in
      enhanced cases. The IC and NIC<formula>_{VP}</formula> of malignant nodules were
      significantly lower than benign nodules in noncontrast and venous phase (VP)
      (P=0.000). The optimal IC and NIC<formula>_{VP}</formula> threshold was 0.68
      mg/mL and 0.38, achieving 74.3% and 76.9% sensitivity, 66.7% and 80.0%
      specificity, respectively. For multivariate analysis, the area under ROC (AUC)
      was 0.88 and 0.94 in noncontrast and VP, respectively. Sensitivities of 77.1% and
      84.6%, and specificities of 84.5% and 88.0% were achieved. CONCLUSION: Gemstone
      spectral CT can generally evaluate the abnormal iodine content in thyroid
      disease. Lower iodine can help differentiating malignant from benign nodules. A
      comprehensive analysis combining spectrum parameters and morphological
      characteristics is suggested in differential diagnosis.

PMID- 25567407
TI  - Computer simulation of a backscattered X-ray fluorescence system.
AB  - An EGSnrc user code is developed to simulate a backscattered geometry in vivo x
      ray fluorescence system for the measurement of platinum concentration in head and
      neck tumours. The user code is fundamentally based on a previous study which used
      the EGS4 Monte Carlo code. The new user code, which we have developed in this
      study, has new improvements which made it able to simulate the process of photon
      transportation through the different components of the modelled x-ray
      fluorescence system. The simulation process included modelling of the photon
      source, collimators, phantoms and detector. Simulation results were compared and
      evaluated against x-ray fluorescence data obtained experimentally from an
      existing system developed by the Swansea In vivo Analysis and Cancer Research
      Group. In addition, simulation results of this study were also compared with our
      previous study in which the EGS4 user code was used. Comparison between results
      has shown that the new EGSnrc user code was able to reproduce the spectral shape
      obtained using the experimental x-ray fluorescence system. The area under the
      Compton peak differs by 2.5% between the experimental measurement and the EGSnrc
      simulation. Similarly, the area under the two Pt Kalpha peaks differs by 2.3% and
      2.2%. 

PMID- 25567408
TI  - A simulation-based study on the influence of beam hardening in X-ray computed
      tomography for dimensional metrology.
AB  - X-ray computed tomography (CT) is a radiographic scanning technique for
      visualising cross-sectional images of an object non-destructively. From these
      cross-sectional images it is possible to evaluate internal dimensional features
      of a workpiece which may otherwise be inaccessible to tactile and optical
      instruments. Beam hardening is a physical process that degrades the quality of CT
      images and has previously been suggested to influence dimensional measurements.
      Using a validated simulation tool, the influence of spectrum pre-filtration and
      beam hardening correction are evaluated for internal and external dimensional
      measurements. Beam hardening is shown to influence internal and external
      dimensions in opposition, and to have a greater influence on outer dimensions
      compared to inner dimensions. The results suggest the combination of spectrum pre
      filtration and a local gradient-based surface determination method are able to
      greatly reduce the influence of beam hardening in X-ray CT for dimensional
      metrology. 

PMID- 25567409
TI  - Distributed CT image reconstruction algorithm based on the alternating direction
      method.
AB  - With the development of compressive sensing theory, image reconstruction from few
      view projections has been paid considerable research attention in the field of
      computed tomography (CT). Total variation (TV)-based CT image reconstruction has
      been shown experimentally to be capable of producing accurate reconstructions
      from sparse-view data. Motivated by the need of solving few-view reconstruction
      problem with large scale data, a general block distribution reconstruction
      algorithm based on TV minimization and the alternating direction method (ADM) has
      been developed in this study. By utilizing the inexact ADM, which involves
      linearization and proximal point techniques, the algorithm is relatively simple
      and hence convenient for the derivation and distributed implementation. And
      because the data as well as the computation are distributed to individual nodes,
      an outstanding acceleration factor is achieved. Experimental results demonstrate
      that the proposed method can accelerate the alternating direction total variation
      minimization (ADTVM) algorithm with nearly no loss of accuracy, which means
      compared with ADTVM, the proposed algorithm has a better accuracy with same
      running time. 

PMID- 25567410
TI  - Effect of local mild hypothermia on regional cerebral blood flow in patients with
      acute intracerebral hemorrhage assessed by 99mTc-ECD SPECT imaging.
AB  - OBJECTIVE: This study aimed to observe the effect of local mild hypothermia on
      regional cerebral blood flow (rCBF) after acute intracerebral hemorrhage (ICH)
      and to evaluate its relation to clinical outcome in patients with ICH. METHODS:
      36 CT proven ICH patients with Glasgow coma scale (GCS) score of 5 or more were
      randomly assigned to 2 group: local mild hypothermia with conventional mannitol
      (Group A) or conventional mannitol (Group B). SPECT study was performed at day 7
      after therapy. The SPECT images were semi-quantitatively analyzed, and the
      radioactivity ratios of lesion to normal tissue (L/NT) were calculated. National
      Institutes of Health Stroke Scale (NIHSS) were used in evaluation at days 14 and
      21 after therapy. RESULTS: There were significant differences in NIHSS score at
      days 14 and 21, and the L/NT ratios between the groups A and B (P < 0.05). Based
      on GCS, more patients in the group A showed favorable outcomes than patients in
      the group B (P < 0.05). Furthermore, the L/NT ratios significantly increased in
      patients with favorable outcomes compared to poor outcomes. Changes in NIHSS
      score at days 14 and 21 were closely negatively correlated with the L/NT ratios
      in the groups A and B (r= -0.58, -0.61, and -0.52, -0.75, respectively, P <
      0.05). CONCLUSION: Local mild hypothermia could significantly increase rCBF and
      improve clinical outcome in ICH patients as evaluated by
      <formula>^{99m}</formula>Tc-ECD SPECT study.

PMID- 25567411
TI  - Optical properties of tissues quantified using morphological granulometry from
      phase-contrast images of thin tissue samples.
AB  - A method combining morphological granulometry with Mie theory to determine
      optical scattering in biological tissues was proposed. Otsu's method was applied
      to binarize phase-contrast images. Binary morphological granulometry was used to
      estimate size density distribution of the tissue samples based on the binary
      phase-contrast images. Our results showed that the optical parameters associated
      with light scattering in tissue could be quantitatively determined by combining
      size density distribution with Mie theory. It was suggested that this unique
      method could be used to characterize biological tissues for disease diagnosis. 

PMID- 25567412
TI  - The effects of golf training in patients with stroke: a pilot study.
AB  - BACKGROUND: Stroke is the most common neurological disease and the primary cause
      of lifelong disability in industrialized countries. Because of this it is
      important to investigate any kind of successful therapy. METHODS: From the 24
      recruited stroke patients who were between 23 and 72 years old, 14 patients were
      separated either in a golf training group (EG), or a social communication meeting
      (CG). Both groups met for one hour sessions, twice a week, for ten weeks. All
      participants completed assessment tests before and after the experimental period:
      cognitive tests measuring attention (Go/No-Go task), visual-spatial memory (Block
      Tapping test) and mental rotation performance (MRT); a balance test (Berg Balance
      Scale), and an emotional well-being test (CES-D-Scale). RESULTS: The results show
      that both groups improved in the CES Scale, the block-tapping test and the
      balance test. In addition, stroke patients who received a golf training showed a
      significant improvement in the MRT comparing to the control group (CG).
      CONCLUSION: It is indicated that golf training can improve visual imagery ability
      in stroke patients, even late after stroke.

PMID- 25567413
TI  - Hip joint degeneration due to cam impingement: a finite element analysis.
AB  - The goal of this study was to investigate the impact of cam impingement, a
      biomechanical risk factor, on hip joint degeneration and ultimately coxarthrosis.
      3D finite element solid models of a healthy and a pathologic hip were developed
      based on clinical reports. The biphasic characteristics of cartilaginous tissues
      were considered to identify localised solid matrix overloading during normal
      walking and sitting down (SD). Localised femoral intrusion at the anterior
      superior pelvic horn was revealed in the pathologic hip during SD, where the
      radial and meridional solid stresses in the acetabular cartilage and
      circumferential solid stresses within the acetabular labrum increased by 3.7, 1.5
      and 2.7 times, respectively. The increased solid-on-solid stresses, reduction in
      fluid-load support and associated higher friction during articulation may result
      in joint wear and other degenerative changes in the hip. 

PMID- 25567414
TI  - Bioaugmentation of half-matured granular sludge with special microbial culture
      promoted establishment of 2,4-dichlorophenoxyacetic acid degrading aerobic
      granules.
AB  - Aerobic granular sludge degrading recalcitrant compounds are generally hard to be
      cultivated. This study investigated the feasibility of cultivating 2,4
      dichlorophenoxyacetic acid (2,4-D) degrading aerobic granules using half-matured
      sludge granules pre-grown on glucose as the seeds and bioaugmentation with a 2,4
      D degrading strain Achromobacter sp. QXH. Results showed that bioaugmentation
      promoted the steady transformation of glucose-grown granules to 2,4-D degrading
      sludge granules and fast establishment of 2,4-D degradation ability. The 2,4-D
      degradation rate of the bioaugmented granules was enhanced by 36-62 % compared to
      the control at 2,4-D concentrations of 144-565 mg/L on Day 18. The inoculated
      strain was incorporated into the half-matured granules successfully and survived
      till the end of operation (220 days). Sludge granules at a mean size of 420 um
      and capable of utilizing 500 mg/L 2,4-D as the sole carbon source were finally
      obtained. Sludge microbial community shifted slightly during the whole operation
      and the dominant bacteria species belonged to Proteobacteria.

PMID- 25567415
TI  - DOX-Cu9S5@mSiO2-PG composite fibers for orthotopic synergistic chemo- and
      photothermal tumor therapy.
AB  - A composite antitumor drug carrier platform, in which antitumor drug doxorubicin
      (DOX) loaded core-shell structured Cu9S5@mSiO2 nanoparticles were incorporated
      into poly(epsilon-caprolactone) and gelatin to form nanofibrous fabrics using an
      electrospinning process, was successfully assembled. The resultant
      multifunctional spun pieces could be implanted directly to the tumor site of mice
      using surgical procedures to achieve the orthotopic synergistic therapy combining
      the chemotherapy of the controlled release of DOX from mesoporous SiO2 with the
      photothermal treatment through the performance of the photothermal transformation
      of Cu9S5 under 980 nm laser irradiation in vivo. The experimental results in vivo
      demonstrated that the synergistic chemotherapy/photothermal treatment of DOX
      loaded Cu9S5@mSiO2 composite fibers under 980 nm laser irradiation has a more
      efficient tumor suppression effect, compared with a single chemotherapy of DOX
      loaded Cu9S5@mSiO2 composite fibers without the 980 nm laser irradiation or a
      single photothermal treatment from Cu9S5@mSiO2 composite fibers under 980 nm
      laser irradiation. 

PMID- 25567417
TI  - Mechanism of electrically induced photonic band gap broadening in polymer
      stabilized cholesteric liquid crystals with negative dielectric anisotropies.
AB  - We experimentally observed that the photonic band gap (reflection band) of
      polymer stabilized cholesteric liquid crystals with negative dielectric
      anisotropies can be greatly broadened under DC electric fields. We explored the
      underlying mechanism. We found that the dispersed polymer network moved when DC
      voltages were applied across the liquid crystal cell. The motion of the polymer
      network stretched the helical pitch of the liquid crystal on one side of the cell
      and compressed the helical pitch on the other side of the cell. We proposed a
      phenomenological theory to explain the motion of the polymer network and the
      effect of the polymer network on the helical pitch, and this theoretical
      prediction agreed well with the experimental results. 

PMID- 25567416
TI  - Effects of antiepileptic drugs on bone health and growth potential in children
      with epilepsy.
AB  - BACKGROUND: Bone health may be impaired in children with epilepsy. OBJECTIVES:
      Our objective was to characterize bone mineral density (BMD) and bone growth in
      children receiving antiepileptic drugs (AEDs) and to assess the effects of co
      morbidity, vitamin D deficiency, and type of drugs used. DATA SOURCES: Data were
      sourced from PubMed, Embase, and Web of Science. ELIGIBILITY CRITERIA: Cross
      sectional, cohort, case-control, or randomized controlled trials reporting BMD or
      parameters of bone growth. PARTICIPANTS: Children with epilepsy compared with
      controls. INTERVENTIONS: AEDS or ketogenic diet. STUDY APPRAISAL: The studies
      were evaluated by one author. SYNTHESIS METHODS: Studies were categorized as
      reporting reduced BMD or not at any skeletal site as outcome. A logistic
      regression was performed for age, percent boys, study design, type of AED, co
      morbidity or not, and signs of vitamin D deficiency/osteomalacia or not. RESULTS:
      Carbamazepine and valproate were analyzed as monotherapy in 11 studies, and for
      both drugs a limited decrease in BMD seemed present. For oxcarbazepine,
      levetiracetam, phenytoin, phenobarbital, and topiramate, only one study with
      monotherapy was found for each drug, none of which reported decreased bone
      density. Polytherapy with AEDs seemed to be associated with a larger decrease in
      bone density than was monotherapy. Although few studies were available on bone
      growth, these did indicate that bone growth may be impaired among users of AEDs.
      Ketogenic diet may be associated with decreased bone density. The main
      determinant of normal BMD was absence of vitamin D deficiency/osteomalacia.
      LIMITATIONS: The studies differed in skeletal sites studied and most were cross
      sectional. No head-to-head comparisons of AEDs were performed. Children treated
      with polytherapy or ketogenic diet may have more complicated and severe disease
      than those treated with monotherapy. The underlying cause of epilepsy and vitamin
      D deficiency may contribute to impaired bone growth and density. CONCLUSIONS:
      Reduced bone density, impaired bone growth, and vitamin D deficiency may be seen
      in children treated with drugs against epilepsy. IMPLICATIONS: Measures to
      correct vitamin D deficiency, calcium intake should be taken.

PMID- 25567418
TI  - Response-effect compatibility with complex actions: the case of wheel rotations.
AB  - The response-effect compatibility (REC) paradigm provides an elegant tool for
      studying the impact of anticipated action effects on action control. Converging
      evidence for such anticipative processes has mainly emerged from tasks that
      require simple, discrete actions, whereas tasks that require more complex,
      continuous actions such as wheel-rotation responses have yielded discrepant
      results. We investigate the role of two moderating variables that have only
      played a minor role in effect-based theories of human action control and may
      account for this discrepancy: (1) the degree of dimensional overlap (rather than
      its mere presence) and (2) directing attention towards the action effects. The
      results of three experiments suggest that both factors are crucial in determining
      the size of REC effects for continuous wheel-rotation responses: Reliable REC
      effects were obtained, and they were larger with high than with low dimensional
      overlap and when attending to the effects than when not. Thus, the study points
      toward important preconditions that determine whether and how effect
      anticipations affect complex motor actions. 

PMID- 25567419
TI  - Welfare indicators during broiler slaughtering.
AB  - 1. The aim of this study was to identify the most relevant welfare indicators for
      unloading, lairage, stunning, killing and post-mortem inspection in a poultry
      slaughter plant. Different indicators were unloading duration, lairage time,
      environmental variables in the lairage facilities, shackling time and electrical
      variables used in the water bath. 2. Lairage time did not correlate strongly with
      dead on arrival. Heat stress was limited by means of ventilation systems, correct
      cage placement and appropriate stocking density per crate. The acceptable
      shackling period was about 30 s. 3. The presence of a corneal reflex showed that
      an animal was alive, while spontaneous wing flapping, spontaneous eye blinking
      and response to a painful stimulus were regarded as indicators of stunning
      efficiency. 4. It was concluded that the presence of recent traumatic injuries
      during the post-mortem inspection could be a valid means to establish whether
      corrective measures concerning the handling, transport and loading procedures
      should be taken.

PMID- 25567421
TI  - Age-related decline in functional connectivity of the vestibular cortical
      network.
AB  - In the elderly, major complaints include dizziness and an increasing number of
      falls, possibly related to an altered processing of vestibular sensory input. In
      this study, we therefore investigate age-related changes induced by processing of
      vestibular sensory stimulation. While previous functional imaging studies of
      healthy aging have investigated brain function during task performance or at
      rest, we used galvanic vestibular stimulation during functional MRI in a task
      free sensory stimulation paradigm to study the effect of healthy aging on central
      vestibular processing, which might only become apparent during stimulation
      processing. Since aging may affect signatures of brain function beyond the BOLD
      signal amplitude-such as functional connectivity or temporal signal variability-
      we employed independent component analysis and partial least squares analysis of
      temporal signal variability. We tested for age-associated changes unrelated to
      vestibular processing, using a motor paradigm, voxel-based morphometry and
      diffusion tensor imaging. This allows us to control for general age-related
      modifications, possibly originating from vascular, atrophic or structural
      connectivity changes. Age-correlated decreases of functional connectivity and
      increases of BOLD--signal variability were associated with multisensory
      vestibular networks. In contrast, no age-related functional connectivity changes
      were detected in somatosensory networks or during the motor paradigm. The
      functional connectivity decrease was not due to structural changes but to a
      decrease in response amplitude. In synopsis, our data suggest that both the age
      dependent functional connectivity decrease and the variability increase may be
      due to deteriorating reciprocal cortico-cortical inhibition with age and related
      to multimodal vestibular integration of sensory inputs.

PMID- 25567420
TI  - Deficits in task-set maintenance and execution networks in Parkinson's disease.
AB  - Patients with Parkinson's disease have difficulties with self-initiating a task
      and maintaining a steady task performance. We hypothesized that these
      difficulties relate to reorganization in the sensorimotor execution, cingulo
      opercular task-set maintenance, and frontoparietal adaptive control networks. We
      tested this hypothesis using graph theory-based network analysis of a composite
      network including a total of 86 nodes, derived from the three networks of
      interest. Resting-state functional magnetic resonance images were collected from
      30 patients with Parkinson's disease (age 42-75 years, 11 females; Hoehn and Yahr
      score 2-3, average 2.4 +/- 0.4) in their off-medication state and 30 matched
      control subjects (age 44-75 years, 10 females). For each node, we calculated
      strength as a general measure of connectivity, global efficiency and betweenness
      centrality as measures of functional integration, and clustering coefficient and
      local efficiency as measures of functional segregation. We found reduced node
      strength, clustering, and local efficiency in sensorimotor and posterior temporal
      nodes. There was also reduced node strength and betweenness centrality in the
      dorsal anterior insula and temporoparietal junction nodes of the cingulo
      opercular network. These nodes are involved in integrating multimodal
      information, specifically related to self-awareness, sense of agency, and
      ultimately to intact perception of self-in-action. Moreover, we observed
      significant correlations between global disease severity and averaged graph
      metrics of the whole network. In addition to the well-known task-related
      frontostriatal mechanisms, we propose that the resting-state reorganization in
      the composite network can contribute to problems with self-initiation and task
      set maintenance in Parkinson's disease.

PMID- 25567422
TI  - Accuracy of using automated methods for detecting adverse events from electronic
      health record data: a research protocol.
AB  - BACKGROUND: Adverse events are associated with significant morbidity, mortality
      and cost in hospitalized patients. Measuring adverse events is necessary for
      quality improvement, but current detection methods are inaccurate, untimely and
      expensive. The advent of electronic health records and the development of
      automated methods for encoding and classifying electronic narrative data, such as
      natural language processing, offer an opportunity to identify potentially better
      methods. The objective of this study is to determine the accuracy of using
      automated methods for detecting three highly prevalent adverse events: a)
      hospital-acquired pneumonia, b) catheter-associated bloodstream infections, and
      c) in-hospital falls. METHODS/DESIGN: This validation study will be conducted at
      two large Canadian academic health centres: the McGill University Health Centre
      (MUHC) and The Ottawa Hospital (TOH). The study population consists of all
      medical, surgical and intensive care unit patients admitted to these centres
      between 2008 and 2014. An automated detection algorithm will be developed and
      validated for each of the three adverse events using electronic data extracted
      from multiple clinical databases. A random sample of MUHC patients will be used
      to develop the automated detection algorithms (cohort 1, development set). The
      accuracy of these algorithms will be assessed using chart review as the reference
      standard. Then, receiver operating characteristic curves will be used to identify
      optimal cut points for each of the data sources. Multivariate logistic regression
      and the areas under curve (AUC) will be used to identify the optimal combination
      of data sources that maximize the accuracy of adverse event detection. The most
      accurate algorithms will then be validated on a second random sample of MUHC
      patients (cohort 1, validation set), and accuracy will be measured using chart
      review as the reference standard. The most accurate algorithms validated at the
      MUHC will then be applied to TOH data (cohort 2), and their accuracy will be
      assessed using a reference standard assessment of the medical chart. DISCUSSION:
      There is a need for more accurate, timely and efficient measures of adverse
      events in acute care hospitals. This is a critical requirement for evaluating the
      effectiveness of preventive interventions and for tracking progress in patient
      safety through time.

PMID- 25567423
TI  - Abnormal resting state FMRI activity predicts processing speed deficits in first
      episode psychosis.
AB  - Little is known regarding the neuropsychological significance of resting state
      functional magnetic resonance imaging (rs-fMRI) activity early in the course of
      psychosis. Moreover, no studies have used different approaches for analysis of rs
      fMRI activity and examined gray matter thickness in the same cohort. In this
      study, 41 patients experiencing a first-episode of psychosis (including N=17 who
      were antipsychotic drug-naive at the time of scanning) and 41 individually age-
      and sex-matched healthy volunteers completed rs-fMRI and structural MRI exams and
      neuropsychological assessments. We computed correlation matrices for 266 regions
      of-interest across the brain to assess global connectivity. In addition,
      independent component analysis (ICA) was used to assess group differences in the
      expression of rs-fMRI activity within 20 predefined publicly available templates.
      Patients demonstrated lower overall rs-fMRI global connectivity compared with
      healthy volunteers without associated group differences in gray matter thickness
      assessed within the same regions-of-interest used in this analysis. Similarly,
      ICA revealed worse rs-fMRI expression scores across all 20 networks in patients
      compared with healthy volunteers, with posthoc analyses revealing significant
      (p<0.05; corrected) abnormalities within the caudate nucleus and planum
      temporale. Worse processing speed correlated significantly with overall lower
      global connectivity using the region-of-interest approach and lower expression
      scores within the planum temporale using ICA. Our findings implicate dysfunction
      in rs-fMRI activity in first-episode psychosis prior to extensive antipsychotic
      treatment using different analytic approaches (in the absence of concomitant gray
      matter structural differences) that predict processing speed. 

PMID- 25567424
TI  - Childhood trauma and neural responses to personalized stress, favorite-food and
      neutral-relaxing cues in adolescents.
AB  - Previous studies have found childhood trauma to be associated with functional and
      structural abnormalities in corticostriatal-limbic brain regions, which may
      explain the associations between trauma and negative mental and physical health
      outcomes. However, functional neuroimaging of maltreatment-related trauma has
      been limited by largely using generic and predominantly aversive stimuli.
      Personalized stress, favorite-food, and neutral/relaxing cues during functional
      magnetic resonance imaging were used to probe the neural correlates of
      emotional/motivational states in adolescents with varying exposure to
      maltreatment-related trauma. Sixty-four adolescents were stratified into high- or
      low-trauma-exposed groups. Cue-related measures of subjective anxiety and craving
      were collected. Relative to the low-trauma-exposed group, high-trauma-exposed
      adolescents displayed an increased activation of insula, anterior cingulate, and
      prefrontal cortex in response to stress cues. Activation in subcortical
      structures, including the hippocampus, was inversely correlated with subjective
      anxiety in the high- but not the low-trauma-exposed group. The high-trauma
      exposed group displayed hypoactivity of cerebellar regions in response to
      neutral/relaxing cues. No group differences were observed in response to favorite
      food cues. The relationship between trauma exposure and altered cortico-limbic
      circuitry may in part explain the association between childhood trauma and
      heightened vulnerability to emotional disturbances and risky behaviour. This may
      be particularly pertinent during adolescence when such difficulties often emerge.
      Further work is needed to elucidate the mechanism linking trauma to obesity. 

PMID- 25567425
TI  - Antipsychotics and amotivation.
AB  - Antipsychotic drugs are thought to produce secondary negative symptoms, which can
      also exacerbate primary negative symptoms. In the present study, we examined
      whether motivational deficits in particular were related to antipsychotic
      treatment in patients with schizophrenia in a dose-dependent manner. Five hundred
      and twenty individuals with schizophrenia who were receiving antipsychotic
      monotherapy for at least 6 months and followed prospectively were included in the
      present study. Participants were receiving one of five antipsychotic medications
      (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses
      were conducted for patients receiving each drug separately. Analysis of
      covariance models were constructed to examine the effect of antipsychotic dose on
      level of motivational impairment, controlling for selected demographic and
      clinical variables (eg, positive symptoms). Level of motivation, or deficits
      therein, were evaluated using a derived measure from the Quality of Life Scale,
      and in addition with scores derived from the Positive and Negative Syndrome
      Scale. Antipsychotic dose was not related to the level of amotivation for any of
      the medications examined. Moreover, severity of sedation was not significantly
      related to the degree of amotivation. One hundred and twenty-one individuals were
      identified as antipsychotic-free at baseline, and after 6 months of antipsychotic
      treatment, no change in motivation was found. Chronic treatment with
      antipsychotics does not necessarily impede or enhance goal-directed motivation in
      patients with schizophrenia. It is possible that the negative impact of
      antipsychotics in this regard is overstated; conversely, the present results also
      indicate that we must look beyond antipsychotics in our efforts to improve
      motivation. 

PMID- 25567426
TI  - CRF-amplified neuronal TLR4/MCP-1 signaling regulates alcohol self
      administration.
AB  - Alcohol dependence is a complex disorder that initiates with episodes of
      excessive alcohol drinking known as binge drinking. It has a 50-60% risk
      contribution from inherited susceptibility genes; however, their exact identity
      and function are still poorly understood. We report that alcohol-preferring P
      rats have innately elevated levels of Toll-like receptor 4 (TLR4) and monocyte
      chemotactic protein-1 (MCP-1) that colocalize in neurons from the central nucleus
      of the amygdala (CeA) and ventral tegmental area (VTA). To examine the potential
      role of a TLR4/MCP-1 signal, we used Herpes Simplex Virus (HSV) vectors
      (amplicons) that retain in vivo neurotropism. Infusion of amplicons for TLR4 or
      MCP-1 siRNA into the CeA or VTA from the P rats inhibited target gene expression
      and blunted binge drinking. A similarly delivered amplicon for scrambled siRNA
      did not inhibit TLR4 or MCP-1 expression nor reduce binge drinking, identifying a
      neuronal TLR4/MCP-1 signal that regulates the initiation of voluntary alcohol
      self-administration. The signal was sustained during alcohol drinking by
      increased expression of corticotropin-releasing factor and its feedback
      regulation of TLR4 expression, likely contributing to the transition to alcohol
      dependence. 

PMID- 25567429
TI  - One non-interpenetrated chiral porous multifunctional metal-organic framework and
      its applications for sensing small solvent molecules and adsorption.
AB  - The herein obtained multifunctional compound is a promising fluorescent material
      that can give tunable fluorescence emissions by changing the solvent molecules.
      The fluorescence sensing behaviors are different for non-protonic and protonic
      solvents. To date, such a large response range of emission positions for
      fluorescent MOFs has not been reported before. 

PMID- 25567427
TI  - Insula-Dorsal Anterior Cingulate Cortex Coupling is Associated with Enhanced
      Brain Reactivity to Smoking Cues.
AB  - The insula plays a critical role in maintaining nicotine dependence and
      reactivity to smoking cues. More broadly, the insula and the dorsal anterior
      cingulate cortex (dACC) are key nodes of the salience network (SN), which
      integrates internal and extrapersonal information to guide behavior. Thus, insula
      dACC interactions may be integral in processing salient information such as
      smoking cues that facilitate continued nicotine use. We evaluated functional
      magnetic resonance imaging (fMRI) data from nicotine-dependent participants
      during rest, and again when they viewed smoking-related images. Greater insula
      dACC coupling at rest was significantly correlated with enhanced smoking cue
      reactivity in brain areas associated with attention and motor preparation,
      including the visual cortex, right ventral lateral prefrontal cortex, and the
      dorsal striatum. In an independent cohort, we found that insula-dACC connectivity
      was stable over 1-h delay and was not influenced by changes in subjective craving
      or expired carbon monoxide, suggesting that connectivity strength between these
      regions may be a trait associated with heightened cue-reactivity. Finally, we
      also showed that insula reactivity to smoking cues correlates with a rise in cue
      reactivity throughout the entire SN, indicating that the insula's role in smoking
      cue-reactivity is not functionally independent, and may actually represent the
      engagement of the entire SN. Collectively, these data provide a more network
      level understanding of the insula's role in nicotine dependence and shows a
      relationship between inherent brain organization and smoking cue-reactivity. 

PMID- 25567430
TI  - Artificial magnetic field induced by an evanescent wave.
AB  - Cold atomic gases are perfect laboratories for realization of quantum simulators.
      In order to simulate solid state systems in the presence of magnetic fields
      special effort has to be made because atoms are charge neutral. There are
      different methods for realization of artificial magnetic fields, that is the
      creation of specific conditions so that the motion of neutral particles mimics
      the dynamics of charged particles in an effective magnetic field. Here, we
      consider adiabatic motion of atoms in the presence of an evanescent wave.
      Theoretical description of the adiabatic motion involves artificial vector and
      scalar potentials related to the Berry phases. Due to the large gradient of the
      evanescent field amplitude, the potentials can be strong enough to induce
      measurable effects in cold atomic gases. We show that the resulting artificial
      magnetic field is able to induce vortices in a Bose-Einstein condensate trapped
      close to a surface of a prism where the evanescent wave is created. We also
      analyze motion of an atomic cloud released from a magneto-optical trap that falls
      down on the surface of the prism. The artificial magnetic field is able to
      reflect falling atoms that can be observed experimentally. 

PMID- 25567432
TI  - [Unmet needs in clinical research in China].

PMID- 25567428
TI  - Markers of serotonergic function in the orbitofrontal cortex and dorsal raphe
      nucleus predict individual variation in spatial-discrimination serial reversal
      learning.
AB  - Dysfunction of the orbitofrontal cortex (OFC) impairs the ability of individuals
      to flexibly adapt behavior to changing stimulus-reward (S-R) contingencies.
      Impaired flexibility also results from interventions that alter serotonin (5-HT)
      and dopamine (DA) transmission in the OFC and dorsomedial striatum (DMS).
      However, it is unclear whether similar mechanisms underpin naturally occurring
      variations in behavioral flexibility. In the present study, we used a spatial
      discrimination serial reversal procedure to investigate interindividual
      variability in behavioral flexibility in rats. We show that flexibility on this
      task is improved following systemic administration of the 5-HT reuptake inhibitor
      citalopram and by low doses of the DA reuptake inhibitor GBR12909. Rats in the
      upper quintile of the distribution of perseverative responses during repeated S-R
      reversals showed significantly reduced levels of the 5-HT metabolite, 5-hydroxy
      indoleacetic acid, in the OFC. Additionally, 5-HT2A receptor binding in the OFC
      of mid- and high-quintile rats was significantly reduced compared with rats in
      the low-quintile group. These perturbations were accompanied by an increase in
      the expression of monoamine oxidase-A (MAO-A) and MAO-B in the lateral OFC and by
      a decrease in the expression of MAO-A, MAO-B, and tryptophan hydroxylase in the
      dorsal raphe nucleus of highly perseverative rats. We found no evidence of
      significant differences in markers of DA and 5-HT function in the DMS or MAO
      expression in the ventral tegmental area of low- vs high-perseverative rats.
      These findings indicate that diminished serotonergic tone in the OFC may be an
      endophenotype that predisposes to behavioral inflexibility and other forms of
      compulsive behavior. 

PMID- 25567431
TI  - [Focusing on some major challenges in surgical management of thyroid cancer].

PMID- 25567433
TI  - [Management and prognosis of differentiated thyroid carcinoma with tracheal
      invasion].
AB  - OBJECTIVE: To evaluate treatment modalities and prognosis differentiated thyroid
      carcinoma (DTC) with tracheal invasion. METHODS: Clinical data were reviewed and
      analyzed in 50 patients treated for DTC with tracheal invasion between January
      1990 and June 1998. The different surgical modalities were applied according to
      the extent of tracheal invasion: shave excision (20 cases), tracheal sleeve
      resection or tracheal partial resection (23 cases), total laryngectomy or
      laryngeal closure surgery (7 cases). Thirty-eight cases received postoperative
      (131)I therapy. Survival rate was evaluated using the Kaplan-Meier analysis.
      RESULTS: The 5-, 10- and 15-year survival rates of all the cases were 90.0%,
      74.0% and 56.0%, respectively. The 5-, 10- and 15-year survival rates were 94.7%,
      81.6% and 65.8% respectively in 38 cases with postoperative (131)I therapy and
      were 75.0%, 50.0% and 25.0% respectively in 12 cases without postoperative (131)I
      therapy, with statistically significant differences in 5-, 10- or 15-year
      survival rates between the patients of two groups. CONCLUSIONS: The tumors can be
      resected radically by corresponding surgery based on the extent of tracheal
      invasion. Postoperative (131)I therapy can enhance the survival rate of the
      patients with differentiated thyroid carcinoma involving in trachea.

PMID- 25567434
TI  - [Factors related to central lymph node metastasis in different subregions for
      unilateral papillary thyroid carcinoma with clinical N0 stage].
AB  - OBJECTIVE: To study clinicopathologic factors related to central lymph node (CLN)
      metastasis in different subregions for unilateral papillary thyroid carcinoma
      (PTC) with clinical N0. METHODS: A total of 145 PTC cases with clinical N0
      treated in the same group of the department of head and neck surgery, Cancer
      Hospital, Chinese Academy of Medical Science between Jan. 2011 and Jan. 2014 was
      analysed retrospectively. Clinicopathologic factors related to CLN metastasis in
      different subregions were analyzed, including sex, age, tumor size,
      extrathyroidal extension, and multifocal tumor. RESULTS: CLN metastases existed
      in 57.9% (84/145) cases and the incidences of ipsilateral paratracheal,
      pretracheal, and prelaryngeal metastasis were 53.8%, 24.1% and 11.3%
      respectively. Right paratracheal lymph node metastasis occurred in anterior
      (17/38, 44.7%) and posterior (12/38, 31.6%) to the recurrent laryngeal nerve.
      Multivariate analysis indicated that extrathyroidal extension (OR = 4.49, 95%CI
      1.80-11.20, P = 0.001) and tumor size (OR = 2.17, 95%CI 1.06-4.45, P = 0.034)
      were independent risk factors for ipsilateral paratracheal CLN metastasis;
      ipsilateral paratracheal CLN metastasis (OR = 2.12, 95%CI 0.08-4.60, P = 0.003)
      was an independent risk factor for pretracheal CLN metastasis. CONCLUSIONS: A
      high risk of CLN metastasis especially ipsilateral paratracheal metastasis exists
      in DTC with clinical N0. Ipsilateral paratracheal, pretracheal and prelaryngeal
      CLN dissection should be conducted when maximum tumor diameter more than 1 cm or
      extrathyroidal extension. CLN anterior and posterior to the recurrent larygeal
      nerve should be removed simultaneously when the ipsilateral paratracheal CLN
      metastasis at right side. Total thyroidectomy and contralateral paratracheal CLN
      dissection should be conciderded in multifocal tumor.

PMID- 25567435
TI  - [Clinical application of carbon nanoparticles in surgery for papillary thyroid
      carcinoma in young patients].
AB  - OBJECTIVE: To investigate the number of dissected lymph nodes and the incidence
      of injury to parathyroid glands during surgery for papillary thyroid carcinoma
      (DTC) in young patients. METHODS: This study collected clinicopathological data
      of 51 young patients with PTC. Of the 51 patients, 18 patients were classified
      into carbon nanoparticles group (CNP group) and 33 patients into traditional
      surgical group (TS group). The number of dissected lymph nodes and the incidence
      of injury to parathyroid glands were analyzed using Wilcoxon rank sum test and
      chi-square test. RESULTS: There were 16 males and 35 females, with a male/female
      ratio of 1: 2.19. The age ranged from 14 to 29 (25 +/- 3.9) years. There was no
      statistically significant difference in age, gender, T-classification, TNM stage
      and surgical procedures between two groups (P > 0.05). The total number of
      dissected lymph nodes in CNP group was higher than that in TS group (Z = -2.258,
      P < 0.05) . However, significant difference in the total number of metastatic
      lymph nodes between the two groups was not found (Z = -0.396, P > 0.05). In level
      VI, the detected lymph node number of group CNP was higher than that of TS group
      (Z = -2.461, P < 0.05) but there was no significant difference in the detected
      number of metastatic lymph nodes (Z = -1.396, P > 0.05) . The rates of injury to
      parathyroid gland were 5.5% in CNP group and 18.2% in TS group, respectively
      (chi(2) = 1.568, P > 0.05). CONCLUSION: Carbon nanoparticles could be an
      effective lymph nodes tracer applying to PTC operation in young patients.

PMID- 25567436
TI  - [Efficiency of carbon nanoparticles in level VI lymphadenectomy for thyroid
      carcinoma and prevention of postoperative hypoparathyroidism].
AB  - OBJECTIVE: To assess the efficiency of carbon nanoparticle in guiding level VI
      lymphadenectomy and parathyroid preservation in thyroidectomy for carcinoma.
      METHODS: One hundred and nine patients with well differentiated thyroid
      carcinoma, in whom thyroidectomy and bilateral lymphadenectomy for level VI were
      carried out at the same time, were prospectively studied. Fourty-five cases
      received carbon nanoparticle injecion in thyroid consistitued trial group, while
      sixty-four underwent conventional surgery as control group. The numbers of total
      dissected lymph nodes, metastasis lymph nodes, black-stained lymph nodes,
      detected parathyroids and mistakenly removed parathyroids were counted
      respectively. The PTH levels were measured at 1 d, 5 d and 30 d after surgery,
      respectively. Student's t test and Chi-square analysis were used for analyzing
      data. RESULTS: The number of lymph node found in the trial group in level VI was
      checked out as (9.7 +/- 1.7) each side, whereas that of the control group was
      (6.7 +/- 1.9) each side. The discrepancy of two groups was statistical meaningful
      (t = 23.14, P < 0.001). The discrepancy of the rate of lymph node black-stained
      90.5% (738/815), incidence of metastasis of the black-stained lymph nodes 45.9%
      (339/738) and that without black-staining 13.0% (10/77), was statistical
      meaningful (chi(2) = 30.91, P < 0.001). On average, the trial group showed (1.8
      +/- 0.9) parathyroid each side, and had 5.9% (5/84) of mistakenly removed
      incidence , on contrary, the control group showed (1.8 +/- 1.0) parathyroid each
      side, and had 8.2% (11/134) of mistakenly removed incidence averagely as well.
      The discrepancy of two groups was statistical meaningful. In the trial group, the
      amount of PTH 1 d, 5 d and 30 d postoperatively were 7.30, 11.19 and 30.50 ng/L
      respectively, while that of the control group were 7.51, 10.90 and 28.30 ng/L
      respectively. The amount discrepancy between the two groups was not differences.
      No permanent recurrent nerve paralysis was found in both groups. CONCLUSION:
      Carbon nanoparticle may improve the detected rate of metastasis lymph nodes, but
      may not be helpful to the prevention of postoperative hypoparathyrosim.

PMID- 25567437
TI  - [Functional evaluation of auditory cortex by functional magnetic resonance before
      cochlear implantation: a pilot study].
AB  - OBJECTIVE: To investigate the functional evaluation of auditory cortex by
      functional magnetic resonance imaging (fMRI) before cochlear implantation (CI).
      METHODS: Twenty-one children with severe to profound sensorineural hearing loss
      (SNHL) (7 cases with normal inner ear structure, 3 cases with large vestibular
      aqueduct syndrome, 1 case with cochlear nerve hypoplasia) and 7 children with
      normal hearing were examined by fMRI under sedation. The subjects received
      acoustic stimuli at four random frequencies (500, 1 000, 2 000, 4 000 Hz) during
      fMRI examination. Tones were interleaved with silence in a block-periodic fMRI
      design with 16-second on-off intervals.Each stimulus repeated twice and the total
      acquisition time was 4 minutes and 28 seconds. RESULTS: Activation was identified
      in the auditory cortex of the 28 subjects in response to monaural and binaural
      acoustic stimulation, which was shown in the transverse temporal gyrus (Heschl
      gyrus), the thalamus and both.Of the 21 patients with SNHL, contralateral
      dominance was shown in six cases, ipsilateral dominance in five cases and
      bilateral equilibrium in 10 cases when one ear was exposed to the stimuli. Of the
      seven children with normal hearing, contralateral dominance was shown in three
      cases, ipsilateral dominance in two cases and bilateral equilibrium in two
      cases.No significant difference of the activation intensity in auditory cortex
      was shown between children with SNHL and normal hearing (P > 0.05). Good hearing
      recovery was obtained in the 21 patients after CI. No significant difference in
      the level of hearing and speech rehabilitation was shown between children with
      LVAS and with normal inner ear structure.Listening behavior response threshold
      was 55 dBHL in the case with cochlear nerve hypoplasia 10 months after CI.
      CONCLUSIONS: fMRI would be a feasible means of evaluating the function of the
      auditory cortex, which can be used for assessing the function of the entire
      auditory system prior to CI combined with ABR and imaging.

PMID- 25567438
TI  - [The impact of allergic rhinitis on state-trait anxiety].
AB  - OBJECTIVE: To investigate the relationship between the different types of
      allergic rhinitis and anxiety. METHODS: State-trait anxiety (State-Trait Anxiety
      Inventory, STAI) was adopted to 98 cases, moderate to severe persistent allergic
      rhinitis (PAR, male 43 cases, female 55 cases ) and 165 cases of moderate to
      severe intermittent allergic rhinitis (IAR, male 89 cases, female 76 cases ) and
      compared with the Chinese standard norm.SPSS 15.0 software was used to analyze
      the data. RESULTS: There was no significant difference in state anxiety (S-AI)
      and trait anxiety (T-AI) score (P(PAR): 0.411,0.724; P(IAR): 0.400,0.061) between
      male patients with allergic rhinitis (PAR and IAR) and the 1998 Chinese male
      norm. There was no significant difference (P(PAR): 0.503, P(IAR): 0.789) between
      female AR patients and normal in T-AI. The S-AI score was significantly higher in
      female AR patients than that in Chinese women norm scores (P(PAR) = 0.007, P(IAR)
      = 0.004). PAR and IAR showed no significant difference on T-AI and S-AI. (P value
      was 0.748 and 0.967). CONCLUSIONS: Female patients with allergic rhinitis can
      cause anxiety and continued, but there is no obvious anxiety potential in T-AI.
      The male patients do not show significantly different from normal people in terms
      of state and trait anxiety. And then, different types of allergic rhinitis have
      no significant correlation with anxiety.

PMID- 25567439
TI  - [Efficacy of intranasal antihistamine in the treatment of allergic rhinitis: a
      meta-analysis].
AB  - OBJECTIVE: To systematically evaluate the efficacy of intranasal antihistamine in
      the treatment of allergic rhinitis. METHODS: The randomized controlled trials
      (RCT) about intranasal antihistamines for the treatment of allergic rhinitis
      between January 1985 and January 2014 were searched in OVID, PubMed, EMBASE,
      CNKI, WanFang Data and Cochrane Library. Two reviewers independently screened the
      literatures, extracted the data, and evaluated the methodological quality, then
      meta-analysis was performed by using RevMan 5.1 software. RESULTS: A total of
      thirteen RCTs were included. The results of meta-analysis showed that the
      efficacy of intranasal antihistamine group was superior to the placebo group in
      total nasal symptom scores (TNSS), the difference was significant[WMD = -1.96,
      95%CI (-2.06;-1.85), P < 0.01], and individual nasal symptom scores (blocked
      nose, rhinorrhea, and sneezing) [WMD = -0.18, 95%CI (-0.28;-0.08); WMD = -0.45,
      95%CI (-0.52;-0.38); WMD = -0.41, 95%CI (-0.58;-0.24), all P < 0.01], with
      significant differences. There was no significant difference between the
      intranasal antihistamine group and the corticosteroid group in TNSS [WMD = -1.51,
      95%CI (-3.51;0.49), P = 0.14], but the intranasal antihistamines group was
      superior to the corticosteroid group in individual nasal symptom scores (blocked
      nose, rhinorrhea, and sneezing) [WMD = -0.23, 95%CI (-0.40;-0.06); WMD = -0.35,
      95%CI (-0.65;-0.05); WMD = -0.25, 95%CI (-0.42;-0.08), all P < 0.05], with
      significant differences. The intranasal antihistamine group was superior to the
      oral antihistamines group in TNSS [WMD = -0.88, 95%CI (-1.51;-0.25), P < 0.01].
      CONCLUSION: Intranasal antihistamine is effective in the control of nasal
      symptoms in AR patients.

PMID- 25567440
TI  - [Comparison of different continuous positive airway pressure titration methods
      for obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To explore whether there were differences between the results of
      automatic titration and the results of manual titration for positive airway
      pressure treatment in patients with obstructive sleep apnea hypopnea syndrome
      (OSAHS) and its influencing factors, the results might provide a theoretical
      basis for the rational use of two pressure titration methods. METHODS: Sixty one
      patients with OSAHS were included in this study. All patients underwent a manual
      titration and an automatic titration within one week. The clinical informations,
      polysomnography data, and the results of both two titration of all patients were
      obtained for analysis. RESULTS: The overall apnea/hypopnea index was (63.1 +/-
      17.7)/h, with a range of 14.9/h to 110.4/h. The treatment pressure of manual
      titration was (8.4 +/- 2.1) cmH(2)O, which was significantly lower than the
      treatment pressure of automatic titration, (11.5 +/- 2.7) cmH(2)O (t = -9.797, P
      < 0.001). After using a DeltaP of 3 cmH(2)O for the cutoff value (DeltaP was
      defined as the difference of automatic titration and manual titration), it was
      found that the pressure of automatic titration was significantly higher in
      patients with a DeltaP > 3 cmH(2)O than in patients with a DeltaP <= 3 cmH(2)O,
      which was (13.3 +/- 2.3) cmH(2)O vs (10.0 +/- 2.0) cmH(2)O (t = -6.159, P <
      0.001). However, there were no differences for the pressure of manual titration
      between these two groups, which was (8.6 +/- 2.4) cmH(2)O vs (8.3 +/- 2.0)cmH(2)O
      (P > 0.05). There was no significant difference in age, body mass index, neck
      circumference, abdomen circumference, apnea hypopnea index, and arterial oxygen
      saturation between these two groups. CONCLUSIONS: The treatment pressure of
      automatic titration is usually higher than that of manual titration. For patients
      with a high treatment pressure which is derived from automatic titration, a
      suggestion about manual titration could be given to decrease the potential
      treatment pressure of continuous positive airway pressure, which may be helpful
      in improving the comfortableness and the compliance of this treatment.

PMID- 25567441
TI  - [Resection of macrosis benign parapharyngeal neoplasms via oral approach].
AB  - OBJECTIVE: To explore investigate the feasibility of transoral removal of
      macrosis benign neoplasms in parapharyngeal space. METHODS: Sixteen patients with
      well-defined macrosis benign parapharyngeal space tumors treated by surgery from
      January 2005 to December 2012 were enrolled in this study. All patients were
      assessed by CT scan, MRI and CT angiography before surgery. Surgery for the
      tumors with complete peplos, locating at medial side of carotid and accessible
      from the oropharynx was completed with the assistance of endoscope, bipolar
      electrocoagulation or radiofrequency ablation system. RESULTS: All neoplasms were
      removed by transoral approach. Tracheotomy was performed in 4 cases. All patients
      were treated successfully with good postoperative recovery and no significant
      complications. Postoperative pathological examination showed there were 9 cases
      of pleomorphic adenoma, 5 cases of neurilemmoma and 2 cases of neurofibroma. By
      the follows-up of 1-8 years (median 31 months), among 16 cases only one case of
      neurofibroma recurred. CONCLUSION: The transoral removal of macrosis benign
      neoplasms in parapharyngeal space is safe, manimally invasive and feasible in
      selected cases, with a high local control rate and a low surgical complication
      rate.

PMID- 25567442
TI  - [The nucleus origin of acoustically evoked short latency negative response in
      guinea pigs].
AB  - OBJECTIVE: This study established a model of acoustically evoked short latency
      negative response (ASNR) in guinea pigs. Stereotaxic coordinate guided
      electrolytic lesion was applied to animal brainstem nuclei, the vestibular
      nucleus and the cochlear nucleus, to define the neural origin of ASNR. METHODS:
      Twenty four guinea pigs with normal hearing were randomly divided into the
      control group (8 subjects, 16 ears) and the deafened group (16 subjects, 32
      ears). Each animal experienced the auditory brainstem response (ABR) test.
      According to the presence of ASNR, the deafened group was further divided into
      ASNR group and non-ASNR group. Electrolytic lesion was conducted to the
      vestibular nucleus and cochlear nucleus respectively, followed by ABR test. The
      lesion structures were verified by brainstem slice and microscope. RESULTS: In
      deafened group, the ASNR was elicited in 10 ears (31.3%). The ASNR was eliminated
      due to the electrolytic destruction to the vestibular nucleus, but it remained
      unchanged after the same procedure to the cochlear nucleus. CONCLUSION: It is
      clear that the ASNR is originated from the vestibular nucleus, but not the
      cochlear nucleus.

PMID- 25567443
TI  - [Retrospective study on the hearing improvement and postoperative perforation
      rates in 121 myringoplasty cases].
AB  - OBJECTIVE: Retrospectively analyzed the influences of preoperative acoustic
      immittance pressure balance tests and intraoperative wet ear findings in
      myringoplasty surgery results. METHODS: One hundred and twenty-one chronic
      suppurative otitis media patients underwent myringoplasty surgeries were included
      and divided into functional group and non-functional group according to
      preoperative acoustic immittance pressure balance tests. Meanwhile, cases were
      divided into dry ear group and wet ear group according to intraoperative
      findings. Postoperative hearing improvement and perforation rate were compared
      between the two groups. RESULTS: Functional group had 72 cases, including 58 dry
      ears and 14 wet ears. Non-functional group had 46 cases, including 19 dry ears
      and 27 wet ears. Postoperative hearing improvement rate in functional group was
      85.5% (59/69), and 72.1% (31/43) in non-functional group (chi(2) = 2.230, P =
      0.093). Perforation rate in functional group was 16.7% (12/72), significant
      higher when compared with 2.2% (1/46) in non-functional group (chi(2) = 4.626, P
      = 0.015). Postoperative hearing improvement rate in dry ear group was 85.3%
      (64/75), and 71.8% (28/39) in wet ear group (chi(2) = 2.213, P = 0.085) .
      Perforation rate in dry ear group was 12.8% (10/78), and 7.0% (3/43) in wet ear
      group (chi(2) = 0.472, P = 0.377). CONCLUSIONS: Non-functional result of
      preoperative acoustic immittance pressure balance test had significant
      relationship with the intraoperative wet ear findings. It may result in lower
      postoperative hearing level, and lower perforation rate. Large sample studies
      should be carried out in future.

PMID- 25567444
TI  - [Prevalence of sensitization to allergens in 1 139 patients with allergic
      rhinitis in Zhengzhou area].
AB  - OBJECTIVE: To investigate the main allergens in patients with allergic rhinitis
      in Zhengzhou district. METHODS: Twenty standardization allergens were used to
      perform skin prick test in 1 139 patients with allergic rhinitis. The samples
      were divided into four groups according to the age of the patients. The
      distributions of different allergens in the four groups were analyzed. RESULTS:
      The top five inhaled allergens were dermatophagoides farina (920 cases, 80.8%),
      dermatophagoides pteronyssinus (870 cases, 76.4%), cat hair (517 cases, 45.4%),
      herbs (397 cases, 34.9%) and poaceae (353 cases, 31.0%); the top five ingestive
      ones were shrimp (143 cases, 12.6%), peanut (66 cases, 5.8%), egg (56 cases,
      4.9%), carp (51 cases, 4.5%) and meat (48 cases, 4.2%). The distribution of
      allergens was different among the different age groups. CONCLUSION: Dust mites,
      cat hair, herbs and poaceae were the most common allergens in Zhengzhou district.

PMID- 25567445
TI  - [Methods for exposure of recurrent laryngeal nerve in thyroid surgery].
AB  - OBJECTIVE: To evaluate different methods to explose recurrent laryngeal nerve
      (RLN) based on the location of thyroid diseses and anatomic path of the RLN, to
      avoid the RLN damage in thyroid surgery. METHODS: A total of 755 cases underwent
      total lobectomy was studied retrospectively. RLN was explosed in each case.
      RESULTS: A total of 963 RLN was exposed in 755 cases, among those 658 RLN were
      exposed by lateral approach, 106 by inferior approach, and 199 by superior
      approach. It was showed that 694 RLN traveled deep to the inferior throid artery
      and 119 superficial to the artery, 98 through between two branches of the artery,
      and 62 with the cross of the nerve branches and the artery branches. Before
      entering larynx, 578 RLN gave off branches and 385 had no branches. Non-recurrent
      laryngeal nerves were found in 2 cases. There were 6 cases who presented with
      hoarseness after thyroidectomy and undergoing reexploration, among them RLN were
      legated in 4 cases and severed in 2 cases. CONCLUSIONS: The anatomic relation of
      RLN is relatively complicated. Lateral, inferior or superior aproach may be used
      for exposure of RLN to decrease risks of injury to the nerve.

PMID- 25567446
TI  - [Clinicopathological analysis of typical carcinoid primarily originated from
      middle ear, sphenoid and throat].

PMID- 25567447
TI  - [Report of 16 patients with styloid process nonunion].

PMID- 25567448
TI  - [Epithelioid sarcoma of preauricular skin: a case report].

PMID- 25567449
TI  - [Advances in evaluation of thyroid nodules by sonography combined with fine
      needle aspiration].

PMID- 25567450
TI  - [Genetic research progress in hereditary head and neck paragangliomas].

PMID- 25567451
TI  - Free-standing porous carbon nanofiber/ultrathin graphite hybrid for flexible
      solid-state supercapacitors.
AB  - A micrometer-thin solid-state supercapacitor (SC) was assembled using two pieces
      of porous carbon nanofibers/ultrathin graphite (pCNFs/G) hybrid films, which were
      one-step synthesized by chemical vapor deposition using copper foil supported Co
      catalyst. The continuously ultrathin graphite sheet (~ 25 nm) is mechanically
      compliant to support the pCNFs even after etching the copper foil and thus can
      work as both current collector and support directly with nearly ignorable
      fraction in a SC stack. The pCNFs are seamlessly grown on the graphite sheet with
      an ohmic contact between the pCNFs and the graphite sheet. Thus, the accumulated
      electrons/ions can duly transport from the pCNFs to graphite (current collector),
      which results in a high rate performance. The maximum energy density and power
      density based on the whole device are up to 2.4 mWh cm(-3) and 23 W cm(-3), which
      are even orders higher than those of the most reported electric double-layer
      capacitors and pseudocapacitors. Moreover, the specific capacitance of the device
      has 96% retention after 5000 cycles and is nearly constant at various curvatures,
      suggesting its wide application potential in powering wearable/miniaturized
      electronics.

PMID- 25567452
TI  - Evaluation of antibacterial activity and cytocompatibility of ciprofloxacin
      loaded gelatin-hydroxyapatite scaffolds as a local drug delivery system for
      osteomyelitis treatment.
AB  - Surgical debridement of the dead bone and subsequent systemic antibiotic therapy
      is often ineffective in eliminating Staphylococcus aureus infections in
      osteomyelitic patients. The recurrence of S. aureus infection is mainly due to
      the intracellular growth of bacterial colonies within osteoblast cells that
      protect the organism from extracellular host defences and/or antibiotic therapy.
      In this study, porous gelatin-hydroxyapatite (HAP) scaffolds with various amounts
      of ciprofloxacin (1, 2, 5, and 10 wt%) were fabricated by freeze-drying technique
      and the release of the antibiotic was characterized, as was the efficacy of the
      released antibiotic against methicillin-sensitive and methicillin-resistant S.
      aureus. Furthermore, the impact of the released antibiotic on the viability and
      osteogenic differentiation of human adipose-derived mesenchymal stem cells
      (ADMSCs) cultured on the scaffolds were assessed. Finally, the efficacy of the
      released ciprofloxacin to enter the cells and abate intracellularly located S.
      aureus was evaluated. All the groups of CGHA scaffolds displayed sustained
      release of ciprofloxacin against S. aureus for 60 days above the minimum
      inhibitory concentration for the target species with zero-order kinetics and
      Korsmeyer-Peppas models. While comparing, the released antibiotic from CGHA5
      scaffolds was found to be effective at reducing S. aureus through the study
      period, without detrimental effects on human ADMSC viability or osteogenic
      potential. When stem cells internalized with S. aureus were cultured onto the
      drug-loaded scaffolds, a significant reduction in the colony count of
      internalized bacteria was observed, resulting in the osteogenic differentiation
      capability of those cells. Our results clearly demonstrate that the ciprofloxacin
      incorporated gelatin-HAP scaffolds, which were cytocompatible and could target
      both intracellular and extracellular S. aureus, defining its potential to be used
      as local drug delivery system. 

PMID- 25567454
TI  - Polymeric-based particulate systems for delivery of therapeutic proteins.
AB  - Polymeric-based particulate systems have been intensively developed to increase
      the short biological half-life and prevent enzymatic degradation of therapeutic
      proteins. These techniques demonstrate the useful characteristics for the
      delivery of therapeutic proteins and peptides to the targeted site of application
      and prevent the interaction of encapsulated drug with the normal cells. In this
      article, we have described the in depth of different pharmaceutical-based
      techniques that are currently being practiced for efficient delivery of
      therapeutic proteins and peptides. A comprehensive English literature was
      searched using different electronic search databases including PubMed, Science
      Direct, Web of Science, google scholar and library search. Different search terms
      and advanced search were made by combining all the search fields in abstract,
      keywords and/or titles. Findings of various studies that have been discussed in
      this article clearly indicate that polymeric-based techniques can significantly
      increase the therapeutic potentials of incorporated proteins with no known toxic
      effects. These techniques have shown to maintain the stability and retain
      biological activity of protein therapeutics. Hence it can be suggested that
      pharmaceutical-based techniques are promising drug carriers for efficient
      delivery of therapeutic proteins. 

PMID- 25567455
TI  - Therapeutic approach to "diabetic foot" complications.
AB  - The series of ulcers of the lower extremities known as "diabetic foot" is a
      common complication of diabetes and the chief cause of admission to hospital. The
      causes may be numerous but the main ones are distal symmetric neuropathy and
      peripheral obliterative arteriopathy, often complicated by infection. In this
      review, the Authors, after having illustrated the main pathophysiological aspects
      of the diabetic foot, describe the clinical characteristics of the disease,
      focusing particularly on the risk of suprainfection and vascular problems. The
      clinical and therapeutic approach to diabetic foot is also investigated with
      particular reference to the antibiotic treatment of infections and the treatment
      of peripheral arterial disease. Poor tissue repair, persistent inflammation, the
      presence of deep abscesses, osteomyelitis and systemic involvement can lead to a
      very serious clinical picture of gangrene or necrosis, which is initially
      localised but which can extend widely, requiring minor or major amputation
      surgery, in order to radically remove the infected tissue. In conclusion, space
      for discussion is given to the rationale of hyperbaric oxygen therapy, negative
      pressure wound therapy and other advanced therapies that involve the use of
      dermoepidermal equivalents and skin substitutes in addition to gels made of
      platelet-derived growth factors and the epidermal growth factor. Nonetheless,
      prevention is, of course, of fundamental importance, based on an intensive treat
      to-target approach for the treatment of diabetes, on regular examinations of the
      feet, on the stratification of risk and education of the patient, which has
      proved successful in reducing the onset of foot lesions in at least 50% of
      patients. 

PMID- 25567453
TI  - Progerin expression disrupts critical adult stem cell functions involved in
      tissue repair.
AB  - Vascular disease is one of the leading causes of death worldwide. Vascular
      repair, essential for tissue maintenance, is critically reduced during vascular
      disease and aging. Efficient vascular repair requires functional adult stem cells
      unimpaired by aging or mutation. One protein candidate for reducing stem
      cell?mediated vascular repair is progerin, an alternative splice variant of lamin
      A. Progerin results from erroneous activation of cryptic splice sites within the
      LMNA gene, and significantly increases during aging. Mutations triggering
      progerin overexpression cause the premature aging disorder Hutchinson-Gilford
      Progeria Syndrome (HGPS), in which patients die at approximately 13-years of age
      due to atherosclerosis-induced disease. Progerin expression affects tissues rich
      in cells that can be derived from marrow stromal cells (MSCs. Studies using
      various MSC subpopulations and models have led to discrepant results. Using a
      well-defined, immature subpopulation of MSCs, Marrow Isolated Adult Multilineage
      Inducible (MIAMI) cells, we find progerin significantly disrupts expression and
      localization of self-renewal markers, proliferation, migration, and membrane
      elasticity. One potential treatment, farnesyltransferase inhibitor, ameliorates
      some of these effects. Our results confirm proposed progerin-induced mechanisms
      and suggest novel ways in which progerin disturbs critical stem cell functions
      collectively required for proper tissue repair, offering promising treatment
      targets for future therapies. 

PMID- 25567456
TI  - Exacerbations of severe asthma: a focus on steroid therapy.
AB  - Bronchial asthma remains one of the most common chronic diseases in the world;
      approximately 10% of patients shows exacerbations severe enough to be judged life
      threatening, whereas around 2-20% of patients are admitted to the Intensive Care
      Unit (ICU). Acute severe asthma is a dangerous condition where the deterioration
      of the asthmatic exacerbation usually progresses over days or weeks, although in
      a few patients over hours or even minutes. Morbidity and mortality are mainly
      related to the underestimation of the severity of the exacerbation, delay in
      referring to hospital and inadequate emergency treatment. The cornerstone
      measures of therapy for acute severe asthma are oxygen supplementation, as to
      achieve arterial saturation >90%, and repetitive or continuous administration of
      bronchodilators (short-acting inhaled beta2-agonists and ipratropium bromide) and
      corticosteroids. Despite extensive clinical experience in treatment of chronic
      asthma with steroids, there is considerable uncertainty about the accurate use of
      these agents for treatment of acute severe asthma in emergency settings. 

PMID- 25567457
TI  - Chocolate and migraine: the history of an ambiguous association.
AB  - Migraine is a highly prevalent condition and an important cause of disability.
      Although the pathogenesis of this condition is complex and multifaceted, several
      environmental factors have been associated with development and aggravation of
      headache attacks. Among the various foods that have been implicated in migraine,
      chocolate has been regarded as detrimental on the basis of old and mostly
      anecdotal evidence. Therefore, this article is aimed to provide an overview on
      the current scientific evidence about the relationship between chocolate and
      migraine. Taken together, the information gathered from epidemiological and
      provocative studies attests that the potential causal association between
      chocolate and migraine remains largely enigmatic. The analysis of epidemiological
      surveys reveals a highly heterogeneous picture, with frequency of migraine
      episodes attributable to chocolate ranging from 0 to 22.5%. Even in those studies
      reporting a more convincing association, the risk of migraine after chocolate
      ingestion was found to be 2- to 3-fold lower than that reported for exposure to
      other conventional triggers such as stress, fasting, lack of sleep and alcohol
      beverages. The results of the double-blind studies are instead unequivocal, and
      clearly demonstrate that the risk of developing a headache attack after ingestion
      of chocolate is as likely as administering placebo in patients with migraine. It
      can hence be concluded that the widespread belief that chocolate and
      cocoacontaining foods should be absolutely avoided by migraine patients lacks of
      a reliable scientific basis. 

PMID- 25567458
TI  - L-Arginine and vascular diseases: lights and pitfalls!
AB  - L-Arginine, a semi-essential cationic amino acid involved in multiple areas of
      human physiology and metabolism, is a precursor of nitric oxide, and, recently,
      it has been found to crucially influence endothelial function. Arginine appears
      to be safe and effective therapy for many health conditions, particularly
      vascular diseases responsive to modulation of endothelial-derived relaxing factor
      including intermittent claudication, angina pectoris and erectile dysfunction.
      However, L-arginine metabolism is still not fully understood, highlighting a
      complex implication for its pharmacological use in clinical practice. In this
      review, we want to point out the lights and pitfalls of L-arginine as potential
      therapeutic option in vascular disorders. 

PMID- 25567459
TI  - Transient global amnesia.
AB  - Transient Global Amnesia (TGA) is a clinical syndrome characterized by temporary
      inability to form new memories described as anterograde amnesia. It is associated
      with retrograde amnesia and repetitive questioning. During the attack patients
      remain conscious and communicative and personal identity is preserved. Focal
      neurological symptoms and epileptic features are absent and general conditions
      appear intact. The ability to store new memories gradually recovers and subjects
      return to normal conditions except for a substantial amnestic gap for the
      duration of the attack. TGA has an incidence of 3-8 per 100 000 people per year.
      It usually affects patients between the ages of 50 and 70 years, at an average
      age of 61 years; occurrence in patients younger than 40 years of age is rare. The
      rate of recurrence is between 6% and 10% per years. No gender prevalence has been
      recorded. The patients with definite TGA have a very good prognosis; their rate
      of subsequent major vascular events is less than 1% per year. 

PMID- 25567460
TI  - A hand-made supplementary food for malnourished children.
AB  - We tested the possibility to prepare a hyperproteic and hyperenergetic
      supplementary food for malnutrition rehabilitation in children starting from
      available ingredients in popular markets in Sierra Leone. Twelve residents in
      Paediatrics from University of Parma, Italy, prepared in a hospital near the
      capital Freetown with modest technology a mixture of peanut flour, palm oil, milk
      powder, sugar and vitamins to which they gave the name of "Parma pap". Three
      hundred and thirty-two malnourished children (mean age 14+/-6.3 months) who were
      receiving Feeding Program Supplementations (FPS), were enrolled in the study: 177
      participants received randomly FSP portions only (Group 1), and 159 participants
      were treated with FSP regimen plus a supplement of "Parma pap" (Group 2).
      Outcomes of the study were computed as WHZ-score increment (Delta value) by
      subtracting the discharge WHZ-score from the admission WHZ-score. The best Delta
      WHZ-scores (>+4) were recorded among participants of Group 2 (64%) rather than in
      Group 1 (21%; p=0.040). The children receiving FSP portions plus "Parma pap"
      recovered faster (5.54 week on average) than those treated with FSP regimen only
      (8.16 on average). The percentage of children who did not recover was higher in
      Group 1 (25.3%) than in Group 2 (; 13%; p=0.05). A slight positive correlation
      has been found between WHZ-scores at admission and at the end of the study
      (r=0.19; p=0.045). During the experience in Sierra Leone we have had the chance
      to give "Parma pap" to twenty one malnourished children admitted to Xaverian
      Mission in Makeni, northern Sierra Leone, not taking other supplementary food.
      Sixteen of these children recovered in 4.9 week on average and five in 6 to 8
      weeks. Mean Delta-WHZ-scores ranged between + 1 and + 5. The data from the
      present study suggest that "Parma pap" could be an effective additional food to
      FPS regimen in malnutrition recovering. Further researches are needed on the
      contrary to prove if "Parma pap" could be defined as a veritable ready to use
      therapeutic food, although this characteristic seems already to result from the
      experience in Makeni Mission. 

PMID- 25567461
TI  - Proximal row carpectomy in the third millenium: is it still a valid indication?
AB  - Proximal row carpectomy (PRC), which was initially described by Stamm in 1944, is
      a surgical procedure for degenerative disorders of the proximal carpal row of the
      carpus. Despite the good results reported in the literature, this technique has
      been gradually replaced over the years by others considered more modern and
      actual, such as wrist arthroplasty and arthrodesis. In this context the authors
      performed the following study and analyzed retrospectively 14 patients who
      underwent PRC during an eighteen years period, between June 1996 and June 2013,
      in order to determine if this surgical operation can be considered still
      indicated. The results of this study confirm that PRC, more or less associated
      with the use of capsular flaps and/or osteochondral grafts, is nowadays a valid
      and simple procedure in selected patients, ensuring a satisfactory functional
      recovery and regression of pain. 

PMID- 25567462
TI  - Comparison of percutaneous intramedullary Kirschner wire and interfragmentary
      screw fixation of displaced extra-articular metacarpal fractures.
AB  - BACKGROUND AND AIM OF THE WORK: the management of the displaced extra-articular
      metacarpal fractures is still a subject of debate in the literature. The purposes
      of this study were to report the outcomes of unstable extra-articular metacarpal
      fractures treated by using intramedullary Kirschner wires or inter-fragmentary
      screws and to determinate which techniques provide better clinical and
      radiographic results. METHODS: we retrospectively reviewed a series of 49
      consecutive patients operated for 53 closed, unstable metacarpal fractures. The
      fractures were divided into two groups, according to the fixation method used:
      the percutaneous intramedullary K-wire fixation group and the interfragmentary
      screw fixation group. The injuries were classified on the basis of fracture level
      and type. Assessment of patients was carried out according to the Mayo Wrist and
      Dash Scoring systems. Finally, radiographic and clinical outcomes of both groups
      were assessed and compared. RESULTS: there were no significant differences
      between the two groups related to follow-up, hospitalization days, operating
      time, and Mayo Wrist and Dash Scores. Bone union was achieved within 6 weeks in
      all patients. Nine cases of malunion were found, with a mean angular deformity of
      8.33 degrees  (range, 5 degrees -15 degrees ), of which 8 were patients treated
      with K-wires (mean 8.125 degrees ) and 1 with screws (10 degrees ). CONCLUSION:
      our results indicate that both procedures are effective in the treatment of
      displaced extra-articular metacarpal fractures. However, we believe K-wires
      represent the gold standard of treatment for displaced fractures of the
      metacarpal neck. Instead, screws are more effective for spiroid shaft fractures,
      while displaced fractures of the base may be treated with either screws or wires.

PMID- 25567463
TI  - Spinal 1% 2-Chloroprocaine versus general anesthesia for ultra-short outpatient
      procedures: a retrospective analysis.
AB  - INTRODUCTION: 2-Chloroprocaine is a local anesthetic with a very short half-life
      and a favorable evolution of spinal block for ultra-short outpatient procedures.
      The aim of this retrospective study is to evaluate the clinical impact of the
      introduction of spinal 1% 2-chloroprocaine compared to general anesthesia at the
      ARS Medica Clinic (Switzerland). MATERIAL AND METHOD: We retrospectively
      evaluated the charts of all patients who underwent knee arthroscopy under general
      anesthesia (group GA) or spinal 2-chloroprocaine (group SA) between June 2012,
      when chloroprocaine was available for the first time, and December 2012. We
      collected the anesthesia time and the number of patients able to bypass the PACU.
      Moreover, we looked at hospital discharge time and we performed a pharmaco
      economic analysis. RESULTS: 61 charts were evaluated, 5 patients were excluded
      for insufficient data. The anesthesia time was comparable between the two groups.
      All patients in group SA were able to bypass the PACU versus only 18% in group
      GA. We observed a clinically significant reduction in terms of discharge time
      (203 vs 326 minutes) and cost of materials and employers involved patients' care
      (53 vs 78 swiss franks) when spinal 1% 2-chloroprocaine was used. CONCLUSION: The
      right selection of the local anesthetic makes spinal anesthesia a suitable
      anesthetic technique for ultra-short outpatient procedures. If short acting local
      anesthetics are involved, spinal anesthesia could be competitive versus general
      anesthesia.

PMID- 25567464
TI  - Ataxia caused by a single dose of dexketoprofen trometamol.
AB  - Mushroom poisoning is an important reason of plant toxicity. Wild mushrooms that
      gathered from pastures and forests can be dangerous for human health. The
      clinical outcomes and symptoms of mushroom toxicity vary from mild
      gastrointestinal symptoms to acute multiple organ failure. Toxic effects to
      kidney and liver of amatoxin are common but cardiotoxic effects are unusual. In
      this case, we reported the cardiotoxic effect of amatoxin with the elevated
      troponin-I without any additional finding in electrocardiography,
      echocardiography and angiography. 

PMID- 25567465
TI  - Unusual presentation of pediatric acute sphenoid sinusitis.
AB  - BACKGROUND: Sphenoid sinus lesions are rare entities, occurring in 2 - 3% out of
      all paranasal sinus lesions. Isolated oculomotor nerve palsy due to acute
      sphenoid sinusitis is very rare, with only few cases reported in literature.
      METHODS: Retrospective report about a case of isolated acute sphenoid sinusitis
      in a child with a left-sided third cranial nerve paralysis as the only sign at
      presentation. RESULTS: Isolated oculomotor nerve palsy can be the initial sign of
      an isolated acute sphenoid sinusitis in children and it requires a high index of
      suspicion in order to avoid a delay in diagnosis. CONCLUSIONS: Magnetic resonance
      imaging should be promptly performed. Functional endoscopic sinus surgery
      represents the treatment of choice in order to restore sinus drainage and avoid
      further intracranial or ocular complications. The need of serial postoperative
      debridement under general anesthesia should be adequately scheduled and
      previously discussed with parents.

PMID- 25567466
TI  - Elevated cardiac enzymes due to mushroom poisoning.
AB  - Mushroom poisoning is an important reason of plant toxicity. Wild mushrooms that
      gathered from pastures and forests can be dangerous for human health. The
      clinical outcomes and symptoms of mushroom toxicity vary from mild
      gastrointestinal symptoms to acute multiple organ failure. Toxic effects to
      kidney and liver of amatoxin are common but cardiotoxic effects are unusual. In
      this case, we reported the cardiotoxic effect of amatoxin with the elevated
      troponin-I without any additional finding in electrocardiography,
      echocardiography and angiography. 

PMID- 25567467
TI  - Which technique is suitable for management of acute myocardial infarction
      following coronary artery bypass surgery, rescue percutaneous coronary
      intervention or open heart surgery? A case-series studies.
AB  - One of the serious complications followingcoronary artery bypass surgery is
      postoperative acute myocardial infarction commonly due to graft thrombosis,
      kinking, or spasm. Two recommended approaches for management of this event
      includeRescue percutaneous coronary intervention (PCI) and urgent open heart
      surgery. In the present case series, we described and compared early and long
      term results of rescue PCI and reoperation in patients with three-vessel coronary
      artery disease undergoing CABG postoperatively and suffered acute myocardial
      infarction. 

PMID- 25567468
TI  - A neuroleptic malignant-like syndrome (NMLS) in a patient with Parkinson's
      disease resolved with rotigotine: a case report.
AB  - Neuroleptic Malignant-Like Syndrome (NMLS) is a rare, but potentially fatal
      complication of dopaminergic therapy in Parkinson's disease due to a sudden
      withdrawal of dopaminergic therapy. Here, we describe the case of a 79 years old
      woman, with 19 years history of Parkinson disease treated with L-dopa, dopamine
      agonists and MAO inhibitors, whose sudden withdrawal due to lack of therapeutic
      compliance, led to sudden onset of high fever, muscle rigidity, akinesia,
      autonomic dysfunction, impaired level of consciousness, respiratory distress and
      dysphagia with inability to take oral dopaminergic therapy. High blood levels of
      CPK and myoglobinaemia were found. The patient was treated with transdermal
      Rotigotine starting from a dose of 2 mg/24 hours, that was rapidly increased to 6
      mg/24 hours, leading to resolution of the acute disturbances. 

PMID- 25567469
TI  - Diabetic ketoacidosis in a 9 month old child and the journey to 4 years.
AB  - We report a case of diabetes mellitus in a 9-month-old male, a product of a non
      consanguinous marriage with no family history of diabetes mellitus. He presented
      initially with ketoacidosis in our emergency room and recovered from coma after
      48 hours but was discharged after 14 days. He is now 4 years old and doing well
      and caregivers are coping even with the challenges of caring for a very young
      diabetic child. This article will help to build up the data bank for diabetes in
      infancy and childhood in our environment as well as highlight the challenges
      faced by both caregivers and physicians in the management of very young diabetics
      irrespective of socioeconomic status. 

PMID- 25567470
TI  - Neutrophil gelatinase-associated lipocalin (NGAL): a promising biomarker for the
      early diagnosis of acute kidney injury (AKI).
AB  - Acute kidney injury (AKI) is a common complication that occurs in a broad
      spectrum of clinical settings. Cardiac surgery-associated AKI continues to be a
      well-recognized complication of cardiac surgery with high morbidity and
      mortality. The lack of early biomarkers has for long prevented timely
      interventions to mitigate the effects of AKI. Serum creatinine is not a timely
      marker of AKI, so that it cannot be used to set potentially effective therapies
      to treat AKI in patients during phases when the injury is still potentially
      reversible. Neutrophil gelatinase-associated lipocalin (NGAL) has been identified
      as a promising biomarker for early detection of AKI. Several studies have shown
      that NGAL levels significantly increase in AKI patients 24 to 48 hours before a
      detectable increase of serum creatinine. Recent studies also suggest that
      measurements of urinary NGAL levels in patients at risk for cardiac surgery
      associated AKI may facilitate its early diagnosis and allow clinicians to
      implement therapeutic adjustments that have the potential to reverse renal
      cellular damage and minimize further kidney injury. 

PMID- 25567471
TI  - Percutaneous endoscopic gastrostomy with Funada-style gastropexy greatly reduces
      the risk of peristomal infection.
AB  - BACKGROUND AND AIMS: Peristomal wound infections are common complications of
      percutaneous endoscopic gastrostomy (PEG). The Funada-style gastropexy device has
      two parallel needles with a wire loop and suture thread, and was developed about
      20 years ago in Japan. This kit has allowed us to perform dual gastropexy very
      easily; PEG with gastropexy has become a very popular technique in Japan. The
      present study aimed to compare the advantages and disadvantages of PEG with the
      gastropexy technique with the standard 'pull' method. METHODS: We retrospectively
      reviewed 182 consecutive, non-randomized patients undergoing PEG in our hospital,
      and a comparative analysis was made between the gastropexy (87 patients) and non
      gastropexy (95 patients) groups. RESULTS: The rates of patients having erythema
      (11.6% vs. 47.9%; P < 0.001), exudates (2.3% vs. 14.9%; P < 0.01) and infection
      (0% vs. 6.4%; P = 0.01) in the peristomal area were lower in the gastropexy than
      in the non-gastropexy group. The rate of minor bleeding from the peristomal area
      was higher in the gastropexy than in the non-gastropexy group (12.8% vs. 2.1%; P
      < 0.01), but no patient required a blood transfusion. Mean procedure time was
      longer in the gastropexy group than in the non-gastropexy group (31 vs. 24 min; P
      < 0.001). The 30-day mortality rates were 4.7% and 5.3% respectively, and these
      deaths were not related to the gastrostomy procedure. CONCLUSION: PEG with
      gastropexy markedly reduces peristomal inflammation. Although minor bleeding and
      a longer procedure time were disadvantages, there were no severe complications.
      The findings suggested that PEG with Funada-style gastropexy was a safe and
      feasible method for reducing early complications of PEG.

PMID- 25567473
TI  - A happy new year from Thrombosis and Haemostasis. A 5 year reflection from the
      editorial team.

PMID- 25567472
TI  - Optimizing the use of biological therapy in patients with inflammatory bowel
      disease.
AB  - Biological therapy revolutionized the treatment of inflammatory bowel disease
      (IBD) during the last decade. These monoclonal antibodies, which target tumor
      necrosis factor (TNF), integrins or IL12/23, have been approved-or are in
      development for-both Crohn's disease (CD) and ulcerative colitis (UC). Early use
      of these agents taught clinicians that induction and maintenance therapy, coupled
      with immunomodulator agents, reduced the immunogenicity of these agents, and led
      to sustained remission in many patients. More recent data has demonstrated that,
      through dose adjustments, optimizing serum drug levels may also provide more
      durable maintenance of remission, and improved mucosal healing. This review
      examines clinical practices that may enhance clinical outcomes from biological
      therapy in IBD. 

PMID- 25567474
TI  - Editors' Choice papers in Thrombosis and Haemostasis.

PMID- 25567475
TI  - Caffeine increases sugar-sweetened beverage consumption in a free-living
      population: a randomised controlled trial.
AB  - Excessive sugar-sweetened beverage (SSB) consumption has been associated with
      overweight and obesity. Caffeine is a common additive to SSB, and through
      dependence effects, it has the potential to promote the consumption of caffeine
      containing foods. The objective of the present study was to assess the influence
      that caffeine has on the consumption of SSB. Participants (n 99) were blindly
      assigned to either a caffeinated SSB (C-SSB) or a non-caffeinated SSB (NC-SSB)
      group. Following randomisation, all participants completed a 9 d flavour
      conditioning paradigm. They then completed a 28 d ad libitum intake intervention
      where they consumed as much or as little of C-SSB or NC-SSB as desired. The
      amount consumed (ml) was recorded daily, 4 d diet diaries were collected and
      liking of SSB was assessed at the start and end of the intervention. Participants
      (n 50) consuming the C-SSB had a daily SSB intake of 419 (sd 298) ml (785 (sd
      559) kJ/d) over the 28 d intervention, significantly more than participants (n
      49) consuming the NC-SSB (273 (sd 278) ml/d, 512 (sd 521) kJ/d) (P=0.05).
      However, participants who consumed the C-SSB liked the SSB more than those who
      consumed the NC-SSB (6.3 v. 6.0 on a nine-point hedonic scale, P= 0.022). The
      addition of low concentrations of caffeine to the SSB significantly increases the
      consumption of the SSB. Regulating caffeine as a food additive may be an
      effective strategy to decrease the consumption of nutrient-poor high-energy foods
      and beverages.

PMID- 25567476
TI  - Methylnaltrexone to prevent intrathecal morphine-induced pruritus after Caesarean
      delivery: a multicentre, randomized clinical trial.
AB  - BACKGROUND: Intrathecal morphine-induced pruritus is a very common side-effect
      that is difficult to prevent or treat. Central and peripheral mechanisms are
      believed to be involved. The aim of this study was to determine if a peripherally
      acting, MU-opioid antagonist would reduce morphine-induced pruritus. METHODS: We
      conducted a multicentre, randomized, blinded, placebo-controlled trial of women
      having elective Caesarean section under spinal anaesthesia with intrathecal
      morphine 100 MUg. After delivery, participants received either subcutaneous
      methylnatrexone bromide 12 mg (MNTX group, n=69) or saline (placebo group, n=68).
      Pruritus, nausea, pain, analgesic use, and side-effects were assessed at 2, 4, 8,
      and 24 h. The primary outcome was the severity of pruritus (0-10 score). RESULTS:
      One hundred and thirty-seven women completed the study, with five major protocol
      violations. There was no statistically significant difference between the MNTX
      and placebo groups for the median (IQR) pruritus AUC scores [24 (9-47) vs 36 (11
      68), median difference 8.5, 95% confidence interval (CI) 0-20, P=0.09] or the
      worst pruritus score [3 (2-7) vs 5 (2-6), median difference 1, 95% CI 0-2,
      P=0.24]. The incidence of pruritus was 84% in the MNTX group and 88% in the
      placebo group (P=0.48). Analgesic and gastrointestinal outcomes did not
      significantly differ between the groups. CONCLUSIONS: A single dose of
      subcutaneous methylnaltrexone bromide 12 mg did not reduce the overall severity
      or incidence of pruritus. In this study, treatment with a peripherally acting MU
      opioid antagonist was generally ineffective against intrathecal morphine-induced
      pruritus, but a small clinical effect cannot be excluded. CLINICAL TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry
      (ACTRN12611000345987).

PMID- 25567477
TI  - Retinal dysfunction of contrast processing in major depression also apparent in
      cortical activity.
AB  - Depressive disorder is often associated with the subjective experience of altered
      visual perception. Recent research has produced growing evidence for involvement
      of the visual system in the pathophysiology of depressive disorder. Using the
      pattern electroretinogram (PERG), we found reduced retinal contrast response in
      patients with major depression. Based on this observation, the question arises
      whether this change has a cortical correlate. To evaluate this, we analyzed the
      visual evoked potential (VEP) of the occipital cortex in 40 patients with
      depressive disorder and 28 healthy controls. As visual stimuli, checkerboard
      stimuli of 0.51 degrees  check size, 12.5 reversals per second and a contrast of
      3-80% was used. In addition to the PERG, we recorded the VEP with an Oz versus
      FPz derivation. The amplitude versus contrast transfer function was compared
      across the two groups and correlated with the severity of depression, as measured
      by the Hamilton Depression Rating Scale and the Beck Depression Inventory.
      Patients with major depression displayed significantly reduced VEP amplitudes at
      all contrast levels compared to control subjects (p = 0.029). The VEP amplitude
      correlated with psychometric measures for severity of depression. The degree of
      depression reduced the contrast transfer function in the VEP to a lesser extent
      than in the PERG: While the PERG is reduced to ~50%, the VEP is reduced to 75%.
      Our results suggest that depression affects the cortical response in major
      depression, but less so than the retinal responses. Modified contrast adaptation
      in the lateral geniculate nucleus or cortex possibly moderates the increased
      losses in the retina.

PMID- 25567479
TI  - Riboflavin level manipulates the successive developmental sequences in
      Aspergillus nidulans.
AB  - Auxotrophic markers are useful in fungal genetic analysis. Among the auxotrophic
      markers, riboB2 is one of the most commonly used markers in many laboratory
      strains. However, riboB2 mutants in Aspergillus nidulans confer self-sterility
      and thus are unable to form hybrid cleistothecia by outcross when both parent
      strains harbor riboB2 auxotrophic marker under the standard protocol. To assess
      the role of riboflavin during the different developmental stages of A. nidulans,
      the limited concentrations of riboflavin were monitored. The commonly used dosage
      of riboflavin (2.5 ug/ml) in the standard medium recipe is enough for hyphal
      growth and conidiation in the riboflavin auxotrophic riboB2 mutants (enough at
      0.02 and 0.5 MUg/ml, respectively) in A. nidulans. However, the dosage is not
      enough to support mature cleistothecium formation. Furthermore, the self-sterile
      defects in riboB2 mutants on standard medium could be restored by the addition of
      25 MUg/ml riboflavin, although the required riboflavin concentrations are varied
      in different genotype strains in A. nidulans. Most importantly, the outcross
      between riboB2 mutants could also be achieved by the supply of riboflavin in the
      sexual developmental stage. Our results highlight the potential roles of
      auxotrophic markers in the development of fungi and improve the efficiency of the
      genetic analysis in A. nidulans.

PMID- 25567478
TI  - Genetic and clinical risk prediction model for postoperative atrial fibrillation.
AB  - BACKGROUND: Postoperative atrial fibrillation (PoAF) is common after coronary
      artery bypass grafting. We previously showed that atrial fibrillation
      susceptibility single nucleotide polymorphisms (SNPs) at the chromosome 4q25
      locus are associated with PoAF. Here, we tested the hypothesis that a combined
      clinical and genetic model incorporating atrial fibrillation risk SNPs would be
      superior to a clinical-only model. METHODS AND RESULTS: We developed and
      externally validated clinical and clinical/genetic risk models for PoAF. The
      discovery and validation cohorts included 556 and 1164 patients, respectively.
      Clinical variables previously associated with PoAF and 13 SNPs at loci associated
      with atrial fibrillation in genome-wide association studies were considered. PoAF
      occurred in 30% and 29% of patients in the discovery and validation cohorts,
      respectively. In the discovery cohort, a logistic regression model with clinical
      factors had good discrimination, with an area under the receiver operator
      characteristic curve of 0.76. The addition of 10 SNPs to the clinical model did
      not improve discrimination (area under receiver operator characteristic curve,
      0.78; P=0.14 for difference between the 2 models). In the validation cohort, the
      clinical model had good discrimination (area under the receiver operator
      characteristic curve, 0.69) and addition of genetic variables resulted in a
      marginal improvement in discrimination (area under receiver operator
      characteristic curve, 0.72; P<0.0001). CONCLUSIONS: We developed and validated a
      model for the prediction of PoAF containing common clinical variables. Addition
      of atrial fibrillation susceptibility SNPs did not improve model performance.
      Tools to accurately predict PoAF are needed to risk stratify patients undergoing
      coronary artery bypass grafting and identify candidates for prophylactic
      therapies.

PMID- 25567480
TI  - Protein phosphatase 2A is involved in the tyrosine hydroxylase phosphorylation
      regulated by alpha-synuclein.
AB  - alpha-Synuclein (alpha-Syn) plays a crucial role in the pathophysiology of
      Parkinson's disease (PD), the degeneration of dopaminergic neurons. Previous
      studies have shown that alpha-Syn regulates dopamine synthesis by binding to and
      inhibiting tyrosine hydroxylase (TH). In neurons, protein phosphatases (PPs) play
      a prominent role in directing signaling toward survival or degeneration. This
      study was to re-evaluate whether alpha-Syn could regulate the tyrosine
      hydroxylase phosphorylation by protein phosphatase-2A (PP2A) in dopaminergic MN9D
      cells and cortex neurons. Our data demonstrated for the first time that alpha-Syn
      stimulates PP2A activity and reduces phosphorylation of TH through regulating the
      methylation of PP2A in dopaminergic MN9D cells and primary cortex neurons.
      Increased PP2A activity and reduced phosphorylation of PP2A at Y307 (inactive
      form of PP2A) were observed in alpha-Syn overexpression dopaminergic cells (Syn)
      and primary cortex neurons, and the TH phosphorylation relieved by enhancing PP2A
      methylation in Syn group could be abated by using PP inhibitors, okadaic acid
      (OKA). OKA could reduce the cell damage and cell apoptosis induced by alpha-Syn.
      Thus our findings may provide an insight into the complicated pathogenesis of PD
      as well as some clues to the development of novel therapeutic strategies
      targeting at PP2A. 

PMID- 25567482
TI  - Self-assembled gold coating enhances X-ray imaging of alginate microcapsules.
AB  - Therapeutic biomolecules produced from cells encapsulated within alginate
      microcapsules (MCs) offer a potential treatment for a number of diseases. However
      the fate of such MCs once implanted into the body is difficult to establish.
      Labelling the MCs with medical imaging contrast agents may aid their detection
      and give researchers the ability to track them over time thus aiding the
      development of such cellular therapies. Here we report the preparation of MCs
      with a self-assembled gold nanoparticle (AuNPs) coating which results in
      distinctive contrast and enables them to be readily identified using a
      conventional small animal X-ray micro-CT scanner. Cationic Reversible Addition
      Fragmentation chain Transfer (RAFT) homopolymer modified AuNPs (PAuNPs) were
      coated onto the surface of negatively charged alginate MCs resulting in hybrids
      which possessed low cytotoxicity and high mechanical stability in vitro. As a
      result of their high localized Au concentration, the hybrid MCs exhibited a
      distinctive bright circular ring even with a low X-ray dose and rapid scanning in
      post-mortem imaging experiments facilitating their positive identification and
      potentially enabling them to be used for in vivo tracking experiments over
      multiple time-points. 

PMID- 25567481
TI  - Nonvesicular release of ATP from rat retinal glial (Muller) cells is
      differentially mediated in response to osmotic stress and glutamate.
AB  - Retinal glial (Muller) cells release ATP upon osmotic stress or activation of
      metabotropic glutamate receptors. ATP inhibits the osmotic Muller cell swelling
      by activation of P2Y1 receptors. In the present study, we determined the
      molecular pathways of the ATP release from Muller cells in slices of the rat
      retina. Administration of the ATP/ADPase apyrase induced a swelling of Muller
      cells under hypoosmotic conditions, and prevented the swelling-inhibitory effect
      of glutamate, suggesting that swelling inhibition is mediated by extracellular
      ATP. A hypoosmotic swelling of Muller cells was also observed in the presence of
      a blocker of multidrug resistance channels (MK-571), a CFTR inhibitor
      (glibenclamide), and connexin hemichannel blockers (18-alpha-glycyrrhetinic acid,
      100 uM carbenoxolone). The swelling-inhibitory effect of glutamate was prevented
      by MK-571, the connexin hemichannel blockers, and a pannexin-1 hemichannel
      blocker (5 uM carbenoxolone). The p-glycoprotein blocker verapamil had no effect.
      As revealed by single-cell RT-PCR, subpopulations of Muller cells expressed mRNAs
      for pannexin-1 and -2, and connexins 30, 30.3, 32, 43, 45, and 46. The data may
      suggest that rat Muller cells release ATP by multidrug resistance channels, CFTR,
      and connexin hemichannels in response to osmotic stress, while glutamate induces
      a release of ATP via multidrug resistance channels, connexin hemichannels, and
      pannexin-1.

PMID- 25567483
TI  - Variation in healthcare services for specialist genetic testing and implications
      for planning genetic services: the example of inherited retinal dystrophy in the
      English NHS.
AB  - This study aims to identify and quantify the extent of current variation in
      service provision of a genetic testing service for dominant and X-linked retinal
      dystrophies in the English National Health Service (NHS). National audit data
      (all test requests and results (n = 1839) issued between 2003 and 2011) and
      survey of English regional genetic testing services were used. Age- and gender
      adjusted standardised testing rates were calculated using indirect
      standardisation, and survey responses were transcribed verbatim and data collated
      and summarised. The cumulative incidence rate of testing in England was 4.5 per
      100,000 population for males and 2.6 per 100,000 population for females. The
      standardised testing rate (STR) varied widely between regions of England, being
      particularly low in the North-east (STR 0.485), with half as many tests as
      expected based on the size and demographic distribution of the population and
      high in the South-east (STR 1.355), with 36 % more tests than expected.
      Substantial and significantly different rates of testing were found between
      regional populations. Specific policy mechanisms to promote, monitor and evaluate
      the regional distribution of access to genetic and genomic testing are required.
      However, commissioners will require information on the scope and role of genetic
      services and the population at risk of the conditions for which patients are
      tested. 

PMID- 25567484
TI  - Low-cost fabrication technologies for nanostructures: state-of-the-art and
      potential.
AB  - In the last decade, some low-cost nanofabrication technologies used in several
      disciplines of nanotechnology have demonstrated promising results in terms of
      versatility and scalability for producing innovative nanostructures. While
      conventional nanofabrication technologies such as photolithography are and will
      be an important part of nanofabrication, some low-cost nanofabrication
      technologies have demonstrated outstanding capabilities for large-scale
      production, providing high throughputs with acceptable resolution and broad
      versatility. Some of these nanotechnological approaches are reviewed in this
      article, providing information about the fundamentals, limitations and potential
      future developments towards nanofabrication processes capable of producing a
      broad range of nanostructures. Furthermore, in many cases, these low-cost
      nanofabrication approaches can be combined with traditional nanofabrication
      technologies. This combination is considered a promising way of generating
      innovative nanostructures suitable for a broad range of applications such as in
      opto-electronics, nano-electronics, photonics, sensing, biotechnology or
      medicine. 

PMID- 25567486
TI  - Editorial.

PMID- 25567485
TI  - Immediate effects of tooth extraction on ridge integrity and dimensions.
AB  - OBJECTIVES: This study aims to assess possible immediate post-extraction changes
      in ridge integrity and width. METHODS: Tooth extractions (53 teeth in 30 adults)
      were performed following atraumatic techniques. Root trunk and ridge width were
      measured at the crest level in buccolingual direction. Similarly, socket width
      and buccal plate thickness were also determined. Pre- and post-extraction buccal
      plate dehiscence, fenestration, or fracture was recorded. Diameter and length of
      extracted tooth root were also measured. Multinomial logistic regression was used
      to reveal relationships between ridge outcome (expanded, stable, or collapsed
      groups) and assessed tooth/site parameters. RESULTS: Post-extraction, buccal
      plate fracture developed in 5 (9%), dehiscence in 15 (28%), and complete buccal
      plate loss in 2 sites (4%). Following extraction, ridge width was expanded in 30
      (57%), collapsed in 12 (23%), and remained unchanged in 11 (21%) sites. In most
      sites (72%), post-extraction socket size was wider than pre-extraction root trunk
      width (p < 0.0001). Socket size was a statistically significant predictor for
      ridge outcome (expansion or collapse compared to stable) (p < 0.01). CONCLUSION:
      Loss of ridge integrity is uncommon, while ridge width expansion is a common
      finding immediately following tooth extraction. The significance of such
      expansion compared to integrity of socket walls remains to be established.
      CLINICAL RELEVANCE: Tooth extraction approaches that preserve ridge integrity are
      accompanied by mainly ridge expansion in ridge width. The significance of such
      immediate changes for the long-term ridge outcomes (i.e., effect on bone
      remodeling especially in relation to buccal bone integrity) needs further
      investigation.

PMID- 25567487
TI  - Adaptation, extinction and global change.
AB  - We discuss three interlinked issues: the natural pace of environmental change and
      adaptation, the likelihood that a population will adapt to a potentially lethal
      change, and adaptation to elevated CO2, the prime mover of global change.
      Environmental variability is governed by power laws showing that ln difference in
      conditions increases with ln elapsed time at a rate of 0.3-0.4. This leads to
      strong but fluctuating selection in many natural populations.The effect of
      repeated adverse change on mean fitness depends on its frequency rather than its
      severity. If the depression of mean fitness leads to population decline, however,
      severe stress may cause extinction. Evolutionary rescue from extinction requires
      abundant genetic variation or a high mutation supply rate, and thus a large
      population size. Although natural populations can sustain quite intense
      selection, they often fail to adapt to anthropogenic stresses such as pollution
      and acidification and instead become extinct.Experimental selection lines of
      algae show no specific adaptation to elevated CO2, but instead lose their carbon
      concentrating mechanism through mutational degradation. This is likely to reduce
      the effectiveness of the oceanic carbon pump. Elevated CO2 is also likely to lead
      to changes in phytoplankton community composition, although it is not yet clear
      what these will be. We emphasize the importance of experimental evolution in
      understanding and predicting the biological response to global change. This will
      be one of the main tasks of evolutionary biologists in the coming decade. 

PMID- 25567488
TI  - Why is HIV not vector-borne?
AB  - Many pathogens of humans are blood borne, including HIV, Malaria, Hepatitis B and
      C, West Nile virus, Dengue, and other viral hemorrhagic fevers. Although several
      of these pathogens are transmitted by blood-feeding arthropods, HIV is not. A
      number of properties of HIV and its life cycle have been identified as proximate
      explanations for the absence of arthropod transmission, but little consideration
      has been given to why HIV has not evolved this form of transmission. We consider
      the empirical evidence for arthropod transmission, and suggest that mechanical
      transmission has not evolved in HIV because such strains would induce a faster
      onset of AIDS during infection, which would thereby limit their ability to
      spread. On the other hand, it is not as clear why biological transmission has not
      occurred. Available data suggests that a lack of appropriate genetic variation in
      HIV is one explanation, but it is also possible that a conflict between natural
      selection occurring within and between infected individuals has prevented its
      evolution instead. We discuss the potential significance of these ideas, and
      argue that taking such an evolutionary perspective broadens our understanding of
      infectious diseases and the potential consequences of public health
      interventions. 

PMID- 25567490
TI  - Virulence and resistance in a mosquito-microsporidium interaction.
AB  - We review the results of a series of experiments involving Aedes aegypti and its
      microsporidian parasite Vavraia culicis to illustrate how intra-specific
      competition and parasitism shape life history traits. More specifically these
      experiments showed that some major components of virulence are host condition
      dependent in this system, while others are not. We also briefly discuss the ways
      through which V. culicis modifies the physiological functioning of its host. We
      discuss the implications of these results for studies of host - parasite
      interactions in general and propose ways through which our studies could
      contribute to vector control and management programs. 

PMID- 25567491
TI  - Pathogen evolution across the agro-ecological interface: implications for disease
      management.
AB  - Infectious disease is a major causal factor in the demography of human, plant and
      animal populations. While it is generally accepted in medical, veterinary and
      agricultural contexts that variation in host resistance and pathogen virulence
      and aggressiveness is of central importance to understanding patterns of
      infection, there has been remarkably little effort to directly investigate causal
      links between population genetic structure and disease dynamics, and even less
      work on factors influencing host-pathogen coevolution. The lack of empirical
      evidence is particularly surprising, given the potential for such variation to
      not only affect disease dynamics and prevalence, but also when or where new
      diseases or pathotypes emerge. Increasingly, this lack of knowledge has led to
      calls for an integrated approach to disease management, incorporating both
      ecological and evolutionary processes. Here, we argue that plant pathogens
      occurring in agro-ecosystems represent one clear example where the application of
      evolutionary principles to disease management would be of great benefit, as well
      as providing model systems for advancing our ability to generalize about the long
      term coevolutionary dynamics of host-pathogen systems. We suggest that this is
      particularly the case given that agro-ecological host-pathogen interactions
      represent a diversity of situations ranging from those that only involve
      agricultural crops through to those that also include weedy crop relatives or
      even unrelated native plant communities. We begin by examining some of the
      criteria that are important in determining involvement in agricultural pathogen
      evolution by noncrop plants. Throughout we use empirical examples to illustrate
      the fact that different processes may dominate in different systems, and suggest
      that consideration of life history and spatial structure are central to
      understanding dynamics and direction of the interaction. We then discuss the
      implications that such interactions have for disease management in agro
      ecosystems and how we can influence those outcomes. Finally, we identify several
      major gaps where future research could increase our ability to utilize
      evolutionary principles in managing disease in agro-ecosystems. 

PMID- 25567489
TI  - The great opportunity: Evolutionary applications to medicine and public health.
AB  - Evolutionary biology is an essential basic science for medicine, but few doctors
      and medical researchers are familiar with its most relevant principles. Most
      medical schools have geneticists who understand evolution, but few have even one
      evolutionary biologist to suggest other possible applications. The canyon between
      evolutionary biology and medicine is wide. The question is whether they offer
      each other enough to make bridge building worthwhile. What benefits could be
      expected if evolution were brought fully to bear on the problems of medicine? How
      would studying medical problems advance evolutionary research? Do doctors need to
      learn evolution, or is it valuable mainly for researchers? What practical steps
      will promote the application of evolutionary biology in the areas of medicine
      where it offers the most? To address these questions, we review current and
      potential applications of evolutionary biology to medicine and public health.
      Some evolutionary technologies, such as population genetics, serial transfer
      production of live vaccines, and phylogenetic analysis, have been widely applied.
      Other areas, such as infectious disease and aging research, illustrate the
      dramatic recent progress made possible by evolutionary insights. In still other
      areas, such as epidemiology, psychiatry, and understanding the regulation of
      bodily defenses, applying evolutionary principles remains an open opportunity. In
      addition to the utility of specific applications, an evolutionary perspective
      fundamentally challenges the prevalent but fundamentally incorrect metaphor of
      the body as a machine designed by an engineer. Bodies are vulnerable to disease -
      and remarkably resilient - precisely because they are not machines built from a
      plan. They are, instead, bundles of compromises shaped by natural selection in
      small increments to maximize reproduction, not health. Understanding the body as
      a product of natural selection, not design, offers new research questions and a
      framework for making medical education more coherent. We conclude with
      recommendations for actions that would better connect evolutionary biology and
      medicine in ways that will benefit public health. It is our hope that faculty and
      students will send this article to their undergraduate and medical school Deans,
      and that this will initiate discussions about the gap, the great opportunity, and
      action plans to bring the full power of evolutionary biology to bear on human
      health problems. 

PMID- 25567493
TI  - Conservation genetics as applied evolution: from genetic pattern to evolutionary
      process.
AB  - Conservation genetics can be seen as the effort to influence the evolutionary
      process in ways that enhance the persistence of populations. Much published
      research in the field applies genetic sampling techniques to infer population
      parameters from the patterns of variation in threatened populations. The limited
      resolution of these inferences seems to yield limited confidence which results in
      conservative policy recommendations. As an alternative, I suggest that
      conservation genetics focus on the relationships between those variables
      conservationists can control, and the probability of desirable evolutionary
      outcomes. This research would involve three phases - a greater use of existing
      evolutionary theory; testing management options using experimental evolution; and
      'field trials' under an adaptive management framework. It would take a
      probabilistic approach that recognizes the stochasticity inherent in evolutionary
      change. This would allow a more nuanced approach to conservation policy than rule
      of thumb guidelines. Moreover, it would capitalize on the fact that evolution is
      a unifying theory in biology and draw on the substantial body of evolutionary
      knowledge that has been built up over the last half a century. 

PMID- 25567492
TI  - Evolutionary concepts in predicting and evaluating the impact of mass
      chemotherapy schistosomiasis control programmes on parasites and their hosts.
AB  - Schistosomiasis is a parasitic disease of significant medical and veterinary
      importance in many regions of the world. Recent shifts in global health policy
      have led towards the implementation of mass chemotherapeutic control programmes
      at the national scale in previously 'neglected' countries such as those within
      sub-Saharan Africa. Evolutionary theory has an important role to play in the
      design, application and interpretation of such programmes. Whilst celebrating the
      rapid success achieved to date by such programmes, in terms of reduced infection
      prevalence, intensity and associated human morbidity, evolutionary change in
      response to drug selection pressure may be predicted under certain circumstances,
      particularly in terms of the development of potential drug resistance,
      evolutionary changes in parasite virulence, transmission and host use, and/or
      competitive interactions with co-infecting pathogens. Theoretical and empirical
      data gained to date serve to highlight the importance of careful monitoring and
      evaluation of parasites and their hosts whenever and wherever chemotherapy is
      applied and where parasite transmission remains. 

PMID- 25567494
TI  - Adaptation, migration or extirpation: climate change outcomes for tree
      populations.
AB  - Species distribution models predict a wholesale redistribution of trees in the
      next century, yet migratory responses necessary to spatially track climates far
      exceed maximum post-glacial rates. The extent to which populations will adapt
      will depend upon phenotypic variation, strength of selection, fecundity,
      interspecific competition, and biotic interactions. Populations of temperate and
      boreal trees show moderate to strong clines in phenology and growth along
      temperature gradients, indicating substantial local adaptation. Traits involved
      in local adaptation appear to be the product of small effects of many genes, and
      the resulting genotypic redundancy combined with high fecundity may facilitate
      rapid local adaptation despite high gene flow. Gene flow with preadapted alleles
      from warmer climates may promote adaptation and migration at the leading edge,
      while populations at the rear will likely face extirpation. Widespread species
      with large populations and high fecundity are likely to persist and adapt, but
      will likely suffer adaptational lag for a few generations. As all tree species
      will be suffering lags, interspecific competition may weaken, facilitating
      persistence under suboptimal conditions. Species with small populations,
      fragmented ranges, low fecundity, or suffering declines due to introduced insects
      or diseases should be candidates for facilitated migration. 

PMID- 25567495
TI  - Genetic, ecological, behavioral and geographic differentiation of populations in
      a thistle weevil: implications for speciation and biocontrol.
AB  - Because weevils are used as biocontrol agents against thistles, it is important
      to document and understand host shifts and the evolution of host-specificity in
      these insects. Furthermore, such host shifts are of fundamental interest to
      mechanisms of speciation. The mediterranean weevil Larinus cynarae normally
      parasitizes either one of two thistle genera, Onopordum and Cynara, being locally
      monophagous. In Sardinia, however, both host genera are used. We used three types
      of data to help understand this complex host use: (i) weevil attack rates on the
      two host genera among 53 different populations in Sardinia and nearby Corsica,
      (ii) host preference in a lab setting, and (iii) genetic (allozyme)
      differentiation among weevil populations exploiting the same or different hosts.
      Using a subset of populations from northern Sardinia, we attempted to relate
      interpopulation differences in host preference to gene flow among populations by
      comparing pairwise differences in oviposition preference (Qst) and in allozyme
      frequencies (Fst). Overall, Qst and Fst were positively correlated. Fst was
      positively correlated with geographic distance among pairs of populations using
      the same host, but not among different-host population pairs. As mating occurs on
      the hosts, this result suggests reinforcement. Genetic evidence indicates Cynara
      as the ancestral host of the weevils from both islands and our current studies
      suggest repeated attempts to colonize Onopordum, with a successful shift in
      Corsica and a partial shift in Sardinia. This scenario would explain why in
      Sardinia the level of attack was higher on Cynara than on Onopordum and why, when
      given a choice in the laboratory, Sardinian weevils preferred Cynara even when
      sampled from Onopordum. The lability of host shifts in L. cynarae supports
      caution in using these or related weevils as biocontrol agents of exotic
      thistles. 

PMID- 25567496
TI  - Consequences of sexual selection for fisheries-induced evolution: an exploratory
      analysis.
AB  - Reproductive behaviour and mating system complexity may influence fisheries
      induced evolution. Mate choice and intrasexual competition might favour late-,
      large-maturing genotypes in contrast to the selection imposed by many fisheries.
      Here, we simulate changes to the mean and variance in body size of Atlantic cod
      (Gadus morhua) concomitant with increased fishing intensity. Comparing selection
      differentials (S) for length under the assumptions that size does and does not
      affect reproductive success, we find that the strength of selection for smaller
      body size associated with increased fishing pressure depends on: (i) the initial
      variance in body size; (ii) changes to the variance in size with increasing
      fishing intensity; and (iii) the influence of size on reproductive success. If
      the initial variability in length is sufficiently high and its coefficient of
      variation (CV) increases with fishing intensity, the predicted evolutionary shift
      towards smaller size generated by fishing is less than that expected under the
      assumption that reproductive success is independent of size. However, if size
      influences reproduction and if the CV in body size declines as fishing pressure
      increases, a trend that may be characteristic of many intensively exploited
      populations, the strength of selection for smaller size is predicted to be
      comparatively rapid. We conclude that fisheries-induced evolution can be
      influenced by changes to the mean and variance of traits under sexual selection,
      and that the benefits of maintaining broad phenotypic variability in traits such
      as body size may be greater than previously thought. 

PMID- 25567498
TI  - Adaptation as a potential response to sea-level rise: a genetic basis for
      salinity tolerance in populations of a coastal marsh fish.
AB  - Relative sea-level rise is resulting in the intrusion of saline waters into
      marshes historically dominated by fresh water. Saltwater intrusions can
      potentially affect resident marsh species, especially when storm-related tidal
      surges cause rapid changes in salinity. We examined the role of historical
      salinity exposure on the survival of Gambusia affinis from two locations in
      coastal Louisiana. At each location, we sampled fish populations from fresh,
      intermediate and brackish marshes. Individuals were then exposed to a salinity of
      250/00 and survival time was measured. We found that fish from brackish and
      intermediate marshes had an increased tolerance to salinity stress relative to
      fish from freshwater environments. We then tested the descendents of fish from
      the fresh and brackish marshes, reared for two generation in fresh water, to
      determine if there was a genetic basis for differential survival. We found that
      descendents of individuals from brackish marshes showed elevated survivals
      relative to the descendents of fish with no historical exposure to salinity. The
      most reasonable mechanism to account for the differences in survival relative to
      historical exposure is genetic adaptation, suggesting that natural selection may
      play a role in the responses of resident marsh fishes to future increases in
      salinity. 

PMID- 25567497
TI  - Temporally stable genetic structure and low migration in an Atlantic salmon
      population complex: implications for conservation and management.
AB  - The evolutionary potential of a population is closely related to two key
      population genetic parameters, namely the effective population size (N e) and
      migration rate (m). Furthermore, knowledge of these parameters is required in
      order to assess potential constraints on local adaptation and for the development
      of biologically sound management strategies. We addressed these key issues by
      investigating the temporal and spatial genetic structure of over 2000 adult
      Atlantic salmon (Salmo salar) collected from 17 sites in the Teno and Naatamo
      rivers in northernmost Europe with up to five time points spanning temporal
      intervals up to 24 years (~4 generations). In all cases except one, local
      populations were found to be temporally stable within the river system. Estimates
      of N e were generally a magnitude larger for the mainstem and headwater
      populations (MS+HW, N e~340-1200) than for the tributary populations (N e~35
      160), thus explaining the higher genetic diversity and lower divergence of the
      MS+HW populations compared to tributaries. The overall migration rates to
      tributaries were low, and in some cases, low enough for local adaptations to
      potentially evolve, despite their lower N e. Signs of a population bottleneck and
      natural recruitment from nearby populations were detected in one local
      population. This highlights a fact which is relevant for the conservation and
      management of highly substructured population systems in general: that even when
      the overall census size is large, local populations can be vulnerable to
      perturbations. To preserve the current and to regain the historical distribution
      of salmon within the river system, we propose that the status of the total
      population complex should be evaluated at the local population level rather than
      from descriptive statistics at the system level. 

PMID- 25567499
TI  - Introgression and dispersal among spotted owl (Strix occidentalis) subspecies.
AB  - Population genetics plays an increasingly important role in the conservation and
      management of declining species, particularly for defining taxonomic units.
      Subspecies are recognized by several conservation organizations and countries and
      receive legal protection under the US Endangered Species Act (ESA). Two
      subspecies of spotted owls, northern (Strix occidentalis caurina) and Mexican (S.
      o. lucida) spotted owls, are ESA-listed as threatened, but the California (S. o.
      occidentalis) spotted owl is not listed. Thus, determining the boundaries of
      these subspecies is critical for effective enforcement of the ESA. We tested the
      validity of previously recognized spotted owl subspecies by analysing 394 spotted
      owls at 10 microsatellite loci. We also tested whether northern and California
      spotted owls hybridize as suggested by previous mitochondrial DNA studies. Our
      results supported current recognition of three subspecies. We also found bi
      directional hybridization and dispersal between northern and California spotted
      owls centered in southern Oregon and northern California. Surprisingly, we also
      detected introgression of Mexican spotted owls into the range of northern spotted
      owls, primarily in the northern part of the subspecies' range in Washington,
      indicating long-distance dispersal of Mexican spotted owls. We conclude with a
      discussion of the conservation implications of our study. 

PMID- 25567500
TI  - Invasion thresholds and the evolution of nonequilibrium virulence.
AB  - The enterprise of virulence management attempts to predict how social practices
      and other factors affect the evolution of parasite virulence. These predictions
      are often based on parasite optima or evolutionary equilibria derived from models
      of host-parasite dynamics. Yet even when such models accurately capture the
      parasite optima, newly invading parasites will typically not be at their optima.
      Here we show that parasite invasion of a host population can occur despite highly
      nonoptimal virulence. Fitness improvements soon after invasion may proceed
      through many steps with wide changes in virulence, because fitness depends on
      transmission as well as virulence, and transmission improvements can overwhelm
      nonoptimal virulence. This process is highly sensitive to mutation supply and the
      strength of selection. Importantly, the same invasion principle applies to the
      evolution of established parasites, whenever mutants arise that overcome host
      immunity/resistance. A host population may consequently experience repeated
      invasions of new parasite variants and possible large shifts in virulence as it
      evolves in an arms race with the parasite. An experimental study of phage lysis
      time and examples of mammalian viruses matching some of these characteristics are
      reviewed. 

PMID- 25567502
TI  - Enlarging brain xanthomas in a patient with cerebrotendinous xanthomatosis.

PMID- 25567501
TI  - Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review.
AB  - INTRODUCTION: Women with inherited metabolic disorders, including those with
      previously life-limiting conditions such as MMA, are reaching child-bearing age
      more often due to advances in early diagnosis and improved pediatric care.
      Information surrounding maternal and fetal complications associated with the
      underlying disorders remains largely unexplored. METHODS: Pregnancies affected by
      maternal MMA were ascertained through study 04-HG-0127 "Clinical and Basic
      Investigations of Methylmalonic Acidemia and Related Disorders"
      (clinicaltrials.gov identifier: NCT00078078) and via literature review. Prenatal
      and delivery records in study participants were reviewed. RESULTS: Seventeen
      pregnancies were identified in women with isolated MMA, including three
      abortions, one termination, and 13 completed pregnancies [three cases with cblA
      (four pregnancies), four cases of mut- (one cobalamin responsive, three non
      responsive), five cases with unknown type of MMA]. Seventeen percent (3/17) of
      the pregnancies resulted in a first trimester abortion, while 38.5% (5/13) of the
      completed pregnancies resulted in preterm deliveries. A cesarean delivery rate of
      53.8% (7/13) was noted among the cohort. Fetal distress or nonreassuring fetal
      status was the indication for 57% (4/7) cesarean deliveries. One patient was
      reported to have metabolic crisis as well as episodes of mild hyperammonemia.
      Malformations or adverse outcomes in the progeny were not observed. CONCLUSION:
      Although there have been a small number of pregnancies identified in women with
      MMA, the cumulative results suggest that the majority of pregnancies can be
      complicated by cesarean delivery and increased risk of prematurity. A pregnancy
      registry could clarify perinatal complications and define management approaches
      needed to ensure optimal maternal and fetal outcomes in this growing patient
      population.

PMID- 25567503
TI  - Plasma renalase in chronic kidney disease: differences and similarities between
      humans and rats.
AB  - Renalase was described in 2005 as a new flavoprotein expressed mainly in the
      kidney that functions as a flavin adenine dinucleotide (FAD)- and nicotinamide
      adenine dinucleotide (NADH)-dependent amine oxidase. In contrast to other
      monoamine oxidases, renalase can be secreted into both plasma and urine where it
      has been suggested to metabolise catecholamines and contribute to blood pressure
      control. Renalase was first reported to be undetectable in patients with chronic
      kidney disease (CKD) and end-stage renal disease (ESRD), suggesting a causal link
      between the reduced plasma renalase levels, increased plasma catecholamine, and
      heightened cardiovascular risk that are well documented in this population.
      Plasma renalase deficiency has been consistently reported in studies using animal
      models of CKD. However, in studies with 3/4 nephrectomised (3/4nx) rats, the
      reduced circulating renalase levels were accompanied by increased plasma renalase
      activity that appeared to be related to decreased inhibition of circulating
      enzyme. By contrast, a series of recent studies in human subjects provides
      evidence suggesting that plasma renalase levels are negatively correlated with
      renal function. Though, similar to that found in the rat remnant kidney, the
      increased plasma renalase activity in patients with ESRD was associated with
      decreased inhibition of the circulating enzyme. 

PMID- 25567504
TI  - Hypertension in patients with severe aortic stenosis: emphasis on
      antihypertensive treatment and the risk of syncope.
AB  - Published guidelines for the management of hypertension (HTN) do not discuss HTN
      in patients with aortic stenosis (AS). Some clinicians have considered severe AS
      to be a relative contraindication to the use of antihypertensive agents. We
      sought to determine the incidence of syncope in AS patients who were treated with
      antihypertensive agents. We identified 89 patients with asymptomatic severe AS
      and normal ejection fraction. The prevalence of HTN, its treatment, and the
      occurrence of syncope was abstracted from medical records. HTN was documented in
      63 of the 89 patients with severe AS; 62 were being treated (mean 2.2 drugs). The
      incidence of syncope (mean follow-up: 44 months) was similar in patients with
      treated HTN compared to those without HTN (8 vs 11%, p=NS). Of the 62 with
      treated HTN, those with syncope were older than those without syncope (88+/- 6 vs
      78 +/- 9 years, p=0.02). When those with treated HTN and syncope were compared to
      an age and sex matched cohort without syncope there were no significant
      differences in severity of AS, ejection fraction, or arterial pressure. Patients
      with treated HTN and syncope had a lower stroke volume index than those without
      syncope (32 +/- 4 vs 40 +/- 6 mL/m2, p=0.01). In conclusion, the risk of syncope
      in patients with severe AS and treated HTN is low and similar to that seen in AS
      patients without HTN. Syncope is related to age, female sex, and a low stroke
      volume index. 

PMID- 25567505
TI  - Treatment of hypertension in chronic kidney disease: does one size fit all? A
      narrative review from a nephrologist's perspective.
AB  - The treatment of hypertension in patients with chronic kidney disease is still
      controversial, particularly in regards to the intensity of blood pressure
      lowering. The 2014 guidelines for the management of hypertension in adults
      released by the Eighth Joint National Committee (JNC 8) have sparked criticism
      from nephrologists, and various societies have issued differing guidelines. In
      this article we present a few case vignettes and provide a brief review of the
      various guidelines, particularly in regards to patients with chronic kidney
      disease. We review some of the landmark trials that have influenced guidelines
      and the practice of nephrology, as well as the limitations of the evidence on
      which the current guidelines are based. We discuss treatment for the patients
      presented in the case vignettes in light of the guidelines and the evidence.
      Finally, it will be clear that there is no single BP goal or single drug that is
      appropriate for all patients, and that our knowledge base for optimal treatment
      of hypertension in chronic kidney disease is still limited. 

PMID- 25567506
TI  - Optogenetics Based Rat-Robot Control: Optical Stimulation Encodes "Stop" and
      "Escape" Commands.
AB  - Electric brain stimulation is frequently used in bio-robot control. However, one
      possible limitation of electric stimulation is the resultant wide range of
      influences that may lead to unexpected side-effects. Although there has been
      prior research done towards optogenetics based brain activation, there has not
      been much development regarding the comparisons between electric and optical
      methods of brain activation. In this study, we first encode "Stop" and "Escape"
      commands by optical stimulation in the dorsal periaqueductal grey (dPAG). The
      rats behavioral comparisons are then noted down under these two methods. The dPAG
      neural activity recorded during optical stimulation suggests rate and temporal
      coding mechanisms in behavioral control. The behavioral comparisons show that
      rats exhibit anxiety under the "Stop" command conveyed through both optical and
      electric methods. However, rats are able to recover more quickly from freezing
      only under optical "Stop" command. Under "Escape" commands, also conveyed through
      optical means, the rat would move with lessened urgency but the results are more
      stable. Moreover, c-Fos study shows the optical stimulation activates restricted
      range in midbrain: the optical stimulation affected only dPAG and its downstreams
      but electric stimulation activates both the upstream and downstream circuits, in
      which the glutamatergic neurons are largely occupied and play important role in
      "Stop" and "Escape" behavior controls. We conclude that optical stimulation is
      more suited for encoding "Stop" and "Escape" commands for rat-robot control. 

PMID- 25567507
TI  - Purification and analysis of the interactions of caspase-1 and ASC for assembly
      of the inflammasome.
AB  - Inflammasomes are intracellular macromolecular complexes assembled to activate
      inflammatory caspases such as caspase-1 and caspase-5, which perform critical
      roles during innate immune response. The NALP3 inflammasome comprises three
      protein components, NALP3, ASC, and caspase-1. ASC, which contains both a pyrin
      domain (PYD) and a caspase recruitment domain (CARD), acts as a bridge to recruit
      NALP3 using the PYD/PYD interaction and to recruit caspase-1 via the CARD/CARD
      interaction. In this study, we successfully purified and characterized ASC CARD
      and caspase-1 CARD. The results showed that ASC CARD was unable to interact with
      caspase-1 CARD in vitro; therefore, we proposed an interaction mode between ASC
      CARD and caspase-1 CARD from a structural based modeling study. 

PMID- 25567508
TI  - Validation of the firefighter WFI treadmill protocol for predicting VO2 max.
AB  - BACKGROUND: The Wellness-Fitness Initiative submaximal treadmill exercise test
      (WFI-TM) is recommended by the US National Fire Protection Agency to assess
      aerobic capacity (VO2 max) in firefighters. However, predicting VO2 max from
      submaximal tests can result in errors leading to erroneous conclusions about
      fitness. AIMS: To investigate the level of agreement between VO2 max predicted
      from the WFI-TM against its direct measurement using exhaled gas analysis.
      METHODS: The WFI-TM was performed to volitional fatigue. Differences between
      estimated VO2 max (derived from the WFI-TM equation) and direct measurement
      (exhaled gas analysis) were compared by paired t-test and agreement was
      determined using Pearson Product-Moment correlation and Bland-Altman analysis.
      Statistical significance was set at P < 0.05. RESULTS: Fifty-nine men performed
      the WFI-TM. Mean (standard deviation) values for estimated and measured VO2 max
      were 44.6 (3.4) and 43.6 (7.9) ml/kg/min, respectively (P < 0.01). The mean bias
      by which WFI-TM overestimated VO2 max was 0.9ml/kg/min with a 95% prediction
      interval of +/-13.1. Prediction errors for 22% of subjects were within +/-5%; 36%
      had errors greater than or equal to +/-15% and 7% had greater than +/-30% errors.
      The correlation between predicted and measured VO2 max was r = 0.55 (standard
      error of the estimate = 2.8ml/kg/min). CONCLUSIONS: WFI-TM predicts VO2 max with
      11% error. There is a tendency to overestimate aerobic capacity in less fit
      individuals and to underestimate it in more fit individuals leading to a
      clustering of values around 42ml/kg/min, a criterion used by some fire
      departments to assess fitness for duty.

PMID- 25567509
TI  - Use of published sickness absence guidelines by human resources professionals.
AB  - BACKGROUND: Sickness absence causes organizational and economic pressures on
      employers. Professional organ izations have published guidelines to inform
      managers of the likely period of time off work resulting from common surgical
      operations and medical conditions. AIMS: To investigate how human resources
      professionals (HRPs) determine the expected length of time off work associated
      with common medical or surgical conditions. METHODS: We sent a hyperlink to an
      internet-based structured closed-ended survey to a cohort of HRPs consisting of
      all HRPs from organizations with a current contract with an National Health
      Service Foundation Trust Occupational Health (OH) department. RESULTS: Of 47
      HRPs, 32 responded (68%). Most of the respondents (84%) used the general
      practitioner's 'fit note' (Med3) as a guide to likely time off work and 47% also
      used personal experience. Twenty-five per cent were aware of medical guidelines
      on time off work and 19% referred to these guidelines, although 50% of these had
      last done so >6 months ago. Eighty-seven per cent of HRPs thought the guidelines
      were easy to interpret and 75% would recommend them to others. However, 75%
      referred employees to the OH department for advice on sickness absence.
      CONCLUSIONS: A high proportion of HRPs used information from the 'fit note' to
      make decisions about sickness absence duration. In addition, most referred
      employees to the OH department for advice on the expected length of time off
      work.

PMID- 25567510
TI  - Identification and quantification of Thiothrix eikelboomii using qPCR for early
      detection of bulking incidents in a full-scale water reclamation plant.
AB  - This study found that the ratio of Thiothrix eikelboomii to total bacterial
      concentrations (TH/TB) (%) was a better indicator of bulking incidents affecting
      effluent quality compared to absolute T. eikelboomii abundance alone. This was
      determined using a genus-specific Thiothrix quantitative PCR primer and probe
      set, which was developed in this study to monitor specific Thiothrix populations
      over a 1-year period. T. eikelboomii was identified as the source of bulking
      incidents based on sequencing of the 16S rRNA gene at a nitrifying-denitrifying
      wastewater treatment plant. Peak T. eikelboomii concentrations observed in March,
      April, and July 2009 were 2.32 * 10(10), 2.64 * 10(10), and 1.84 * 10(10)
      cells/l, respectively. The highest fraction of T. eikelboomii to total bacterial
      population was measured at 0.24% in March, and a ratio >0.19% caused increases of
      suspended solids and biochemical oxygen demand in the secondary effluent.
      Additionally, food/mass ratios, dissolved oxygen concentrations in the anoxic
      selector, and ammonium ion concentrations in the primary effluent were three
      parameters displaying statistically significant correlations (r = 0.40, r = 0.50,
      and r = 0.32, respectively) to Thiothrix spp. abundance in an aeration tank. No
      bulking events caused by T. eikelboomii occurred when the dissolved oxygen
      concentrations in the anoxic selector was maintained at lower than 0.12 mg/l and
      the TH/TB ratios were <0.10%.

PMID- 25567511
TI  - Sustainable source of omega-3 eicosapentaenoic acid from metabolically engineered
      Yarrowia lipolytica: from fundamental research to commercial production.
AB  - The omega-3 fatty acids, cis-5, 8, 11, 14, and 17-eicosapentaenoic acid (C20:5;
      EPA) and cis-4, 7, 10, 13, 16, and 19-docosahexaenoic acid (C22:6; DHA), have
      wide-ranging benefits in improving heart health, immune function, mental health,
      and infant cognitive development. Currently, the major source for EPA and DHA is
      from fish oil, and a minor source of DHA is from microalgae. With the increased
      demand for EPA and DHA, DuPont has developed a clean and sustainable source of
      the omega-3 fatty acid EPA through fermentation using metabolically engineered
      strains of Yarrowia lipolytica. In this mini-review, we will focus on DuPont's
      technology for EPA production. Specifically, EPA biosynthetic and supporting
      pathways have been introduced into the oleaginous yeast to synthesize and
      accumulate EPA under fermentation conditions. This Yarrowia platform can also
      produce tailored omega-3 (EPA, DHA) and/or omega-6 (ARA, GLA) fatty acid mixtures
      in the cellular lipid profiles. Fundamental research such as metabolic
      engineering for strain construction, high-throughput screening for strain
      selection, fermentation process development, and process scale-up were all needed
      to achieve the high levels of EPA titer, rate, and yield required for commercial
      application. Here, we summarize how we have combined the fundamental bioscience
      and the industrial engineering skills to achieve large-scale production of
      Yarrowia biomass containing high amounts of EPA, which led to two commercial
      products, New HarvestTM EPA oil and Verlasso(r) salmon. 

PMID- 25567513
TI  - Beneficial knockouts in Escherichia coli for producing hydrogen from glycerol.
AB  - Glycerol is an inexpensive and abundant source for biofuel production on a large
      scale. Escherichia coli is a robust bacterium for producing hydrogen; however,
      its hydrogen productivity from glycerol is low. In this study, we conducted
      random transposon mutagenesis to identify uncharacterized genes whose
      inactivation is beneficial for hydrogen production from glycerol. Through
      screening, four mutant strains were found that are able to have from 1.3- to 1.6
      fold higher hydrogen productivity (MUmol H2/mg protein) than that of their parent
      strain (p < 0.05). These mutations were identified as aroM, gatZ, ycgR, and yfgI.
      The hydrogen yield (mol H2/mol glycerol consumed) of the aroM, gatZ, ycgR, and
      yfgI strains was 1.7-, 1.4-, 2.4-, and 2.1-fold higher than that of their parent
      strain, respectively. Moreover, a single disruption in these genes resulted in a
      faster cell growth and glycerol consumption under anaerobic conditions. In E.
      coli, AroM is predicted to be involved in the shikimate pathway, GatZ is tagatose
      1,6-bisphosphate aldolase 2 which converts dihydroxyacetone phosphate to 1,6
      biphosphate, and YcgR acts as a molecular brake limiting the swimming speed and
      ATP consumption. So far, the function of YfgI in general and in hydrogen
      production in particular remains unknown.

PMID- 25567512
TI  - Construction and evaluation of a fluorescence-based live attenuated Escherichia
      coli delivery system for generating oral vaccine candidate.
AB  - Enter toxigenic Escherichia coli (ETEC) is a major pathogen of swine industry
      that can have a substantial impact on morbidity and mortality. Therefore, it is
      necessary to develop effective vaccines for the prevention of ETEC infection.
      Live attenuated bacteria delivery system are effective tools for mucosal
      immunization. The purpose of this study was to construct a novel delivery system
      that can present the LTR192G-STb fusion protein as oral vaccine candidate.
      Firstly, the PRPL-mKate2 fluorescent cassette was inserted into the genome (yaiT
      pseudogene) of an attenuated E. coli by homologous recombination methods to
      construct the delivery system O142(yaiT::PRPL-mKate2). Secondly, the oral vaccine
      O142(yaiT:: LT192-STb) (ER-B) was derived for replacing the PRPL-mKate2 by LT192
      STb fusion gene, and then it was tested for its feasibility as oral vaccine
      candidate. Subsequently, BALB/c mice were orogastrically immunized with ER-B.
      Results showed that mice orally immunized with ER-B produced high levels of
      specific IgA and IgG antibodies. The induced antibodies demonstrated neutralizing
      effects to enter toxins LT and STb. In addition, results of cellular immune
      responses showed that stimulation index values of immunized mice were
      significantly higher than the control group (P < 0.05) and with a marked shift
      towards Th 2 immunity. These data indicated that the recombinant E. coli ER-B
      could be a valuable candidate of future vaccines against ETEC infection.

PMID- 25567514
TI  - Recombinant outer membrane protein A induces a protective immune response against
      Escherichia coli infection in mice.
AB  - Pathogenic Escherichia coli (E. coli) is an important infectious Gram-negative
      bacterium causing millions of death every year. Outer membrane protein A (OmpA)
      has been suggested as a potential vaccine candidate for conferring protection
      against bacterial infection. In this study, a universal vaccine candidate for E.
      coli infection was developed and evaluated. Bioinformatics analysis revealed the
      OmpA protein from E. coli shares 96~100%, 90~94%, and 45% identity with Shigella,
      Salmonella, and Pseudomonas strains, respectively. The ompA gene was cloned from
      the genomic DNA of E. coli, and then the OmpA protein was expressed in BL21 (DE3)
      using the auto-induction method. The recombinant OmpA (rOmpA) protein had an
      average molecular weight of 36 kDa with the purity of 93.5%. Immunological
      analysis indicated that the titers of anti-rOmpA sera against rOmpA and whole
      cells were 1:642,000 and 1:140,000, respectively. Moreover, rOmpA not only
      conferred a high level of immunogenicity to protect mice against the challenge of
      E. coli, but also generated cross-protection against Shigella and Salmonella. The
      anti-rOmpA sera could enhance the phagocytic activity of neutrophils against E.
      coli. The survive ratios of mice immunized with rOmpA and PBS were 50% and 20%
      after 48 h post-challenge, indicating mice were protected from E. coli infection
      after immunization with rOmpA. All these results clearly indicate that rOmpA may
      be a promising candidate for the development of a subunit vaccine to prevent E.
      coli infection.

PMID- 25567515
TI  - Distribution of sediment ammonia-oxidizing microorganisms in plateau freshwater
      lakes.
AB  - Both ammonia-oxidizing bacteria (AOB) and archaea (AOA) can play important roles
      in ammonia biotransformation in ecosystems. However, the factors regulating the
      distribution of these microorganisms in lacustrine ecosystems remain essentially
      unclear. The present study investigated the effects of geographic location on the
      distribution of sediment AOA and AOB in 13 freshwater lakes on the Yunnan Plateau
      (China). The spatial dissimilarity in the abundance and structure of sediment AOA
      and AOB communities was observed in these plateau lakes. AOA abundance was
      usually less than AOB abundance, and the AOA/AOB ratio was positively correlated
      with water depth. Nitrososphaera-like AOA occurred in most of the studied lakes
      and were dominant in two lakes. Nitrosospira was the dominant AOB species in most
      of the lakes, while Nitrosomonas showed high abundance only in three lakes. In
      addition, geographic location was found to affect lake sediment AOB community
      structure. 

PMID- 25567516
TI  - A case report of three patients with metastatic gastric cancer on hemodialysis
      who were treated with cisplatin-fluorouracil regimen.
AB  - Gastric carcinoma is the first cause of death worldwide. In previous studies that
      included best supportive care and chemotherapy comparison, chemotherapy survival
      time was four to five months more than best supportive care. This time was
      reported as seven to nine months in cisplatin and fluorouracil therapy. We aimed
      to call attention to non-progression survival time which was being longer with
      cisplatin and fluorouracil therapy in three metastatic gastric carcinoma patients
      who were on hemodialysis due to chronic renal impairment related to diabetic
      nephropathy. We determined that this regimen was well tolerated with
      hemodialysis, and the median time to progression was eight months (range 7-10).
      This time was similar to the time results of previous studies. In our hypothesis,
      hemodialysis may increase the time to progression significantly and we aimed to
      discuss the hypothetical relation between dialysis membrane and circulating tumor
      cells. 

PMID- 25567517
TI  - A single-center evaluation of the risk for colonization or bacteremia with
      piperacillin-tazobactam- and cefepime-resistant bacteria in patients with acute
      leukemia receiving fluoroquinolone prophylaxis.
AB  - Fluoroquinolone prophylaxis is indicated to prevent neutropenic fever in patients
      with acute leukemia. However, fluoroquinolone use has been associated with
      development of multi-drug-resistant Pseudomonas aeruginosa and extended spectrum
      beta-lactamase producing gram-negative bacilli. Due to a presumed risk of multi
      drug resistance associated with fluoroquinolone prophylaxis, patients admitted to
      our hospital with neutropenic fever receive empiric carbapenem therapy until
      cultures are negative for 72 h or identification of an organism. Our study seeks
      to identify the incidence of multi-drug-resistant organism colonization and
      bacteremia among patients who receive fluoroquinolone prophylaxis and to evaluate
      duration of empiric carbapenem therapy. A retrospective review of adult patients
      with acute leukemia receiving a fluoroquinolone as outpatient infection
      prophylaxis, admitted to our tertiary cancer center for treatment of neutropenic
      fever was completed. Surveillance and blood cultures were reviewed for antibiotic
      resistance. Duration of empiric carbapenem therapy was reviewed. One hundred
      patients and 177 admissions for neutropenic fever were included. Six patients
      harbored a piperacillin-tazobactam-resistant organism found during routine
      surveillance. Among these patients, two bacteremias were identified, one of which
      was a piperacillin-tazobactam-resistant organism. Five bacteremias were
      identified among 83 patients with negative surveillance cultures. Among the
      bloodstream infections, five organisms isolated were fluoroquinolone resistant.
      No cefepime-resistant organism was isolated on surveillance or bloodstream
      cultures. Adherence to the institution guideline of narrowing antibiotics after
      72 h of negative cultures occurred in only 13% of neutropenic fever cases. The
      average duration of carbapenem therapy in 177 neutropenic fever episodes was 4.4
      days. Our findings show that among our patient population, there is a low risk of
      bacteremia with a piperacillin-tazobactam-resistant or cefepime-resistant
      organism. However, prompt de-escalation of carbapenem therapy needs to be
      reiterated within hospital practice. 

PMID- 25567518
TI  - Risk factors for developing cardiotoxicity of trastuzumab in breast cancer
      patients: An observational single-centre study.
AB  - BACKGROUND: Trastuzumab is a recombinant humanized monoclonal antibody used to
      treat human epidermal growth factor receptor 2 positive breast cancer, with
      recognized associated cardiotoxicity. In this retrospective observational study,
      we investigated associated cardiotoxicity on clinical outcomes using trastuzumab
      in women referred to our clinic. MATERIALS AND METHODS: The study was made up of
      111 women with human epidermal growth factor receptor 2-overexpressing breast
      cancer who received trastuzumab in the Medical Oncology Department, between 2010
      and 2013. RESULTS: A > 10% reduction of the baseline fraction of the left
      ventricular ejection fraction was observed in 18 (16.21%) women. Two individuals
      (1.8%) suffered from symptomatic heart failure, seven women showed cardiac
      symptoms and nine women showed asymptomatic decline of left ventricular ejection
      fraction. Risk factors for cardiotoxicity in the group included: postmenopausal
      status (p = 0.01), hypertension (p = 0.002), obesity (p = 0.0001), previously
      diagnosed coronary artery disease (p = 0.0001) and smoking (p = 0.03).
      CONCLUSION: The aforementioned factors pose a risk for cardiotoxicity. We found
      postmenopausal status, hypertension, obesity, previous coronary artery disease
      and smoking to be associated with an increased risk of cardiac dysfunction in
      women using trastuzumab. While administering trastuzumab to women who have these
      conditions, one must be aware of the risk of cardiotoxicity of trastuzumab.

PMID- 25567519
TI  - Successful use of palifermin following severe anaphylaxis to pegaspargase in a
      pediatric patient with acute lymphoblastic leukemia.
AB  - Palifermin and pegaspargase are Escherichia coli-derived drug products.
      Hypersensitivity reactions, including anaphylaxis, are frequently reported with
      pegaspargase. In high-risk acute lymphoblasic leukemia (ALL), patients undergoing
      allogeneic hematopoietic stem cell transplant may be treated with palifermin as a
      supportive care measure for mucositis prophylaxis. However, no literature exists
      documenting the cross-reactivity between palifermin and pegaspargase. We report a
      case in which a child with very high-risk ALL having experienced severe
      anaphylaxis with pegaspargase was later successfully treated with palifermin
      during stem cell transplant conditioning. 

PMID- 25567520
TI  - Sorafenib-induced severe urticaria in a patient with hepatocellular cancer.
AB  - Sorafenib which is used in the treatment of renal, thyroid and hepatocellular
      cancers is a multi-targeted tyrosine kinase inhibitor. Though sorafenib is
      associated with some side effects, it is known that sorafenib is generally well
      tolerated compared to other tyrosine kinase inhibitors. In the present case,
      hepatocellular cancer was diagnosed seven months ago. The disease was in stage
      IIIB at the time of diagnosis. Sorafenib was initiated with a dose of 400 mg
      twice daily because of disease progression after two cycles of doxorubicin. The
      reactions on the skin of the arms and the body of the patient occurred in the
      eighth week of treatment. Skin biopsy was performed and urticaria was diagnosed
      after pathologic examination. No other disorders or drugs which may cause
      urticaria were detected in the patient. Skin reactions disappeared one week after
      sorafenib discontinuation without any further intervention. 

PMID- 25567522
TI  - Serum soluble levels of the transmembrane activator and calcium-modulator and
      cyclophilin-ligand interactor in MPO-ANCA-associated renal vasculitis.

PMID- 25567523
TI  - Excess of 210polonium activity in the surface urban atmosphere. Part (1)
      fluctuation of the 210Po excess in the air.
AB  - The concentrations of (210)Pb, (210)Bi, and (210)Po in the urban atmosphere of
      Lodz city were measured from February 2010 to May 2010 and from May 2011 to April
      2012. The seasonal changes in the activity ratios for (210)Po/(210)Pb and
      (210)Bi/(210)Pb indicated that the observed fluctuations were independent of the
      concentration of tropospheric (210)Pb and its decay products, particularly
      (210)Po. A simple calculation method was proposed for the estimation of the
      excess of (210)Po in urban aerosols in relation to the fraction of its activity
      formed from (210)Pb. On the basis of the results obtained, it was concluded that
      a substantial part of the (210)Po in urban air did not come from the decay of
      atmospheric (222)Rn, but rather it was from artificial sources. The highest
      levels of measured total (210)Po activity were observed during the winter period.
      This observation suggests that the main source of (210)Po in the investigated
      region could be related to anthropogenic emissions from domestic heating systems
      and local coal power plants, rather than from other sources, such as soil
      resuspension or stratospheric air intrusion as usually suggested in the
      literature. 

PMID- 25567521
TI  - Genome-wide mRNA expression profiling in vastus lateralis of COPD patients with
      low and normal fat free mass index and healthy controls.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) has significant systemic
      effects beyond the lungs amongst which muscle wasting is a prominent contributor
      to exercise limitation and an independent predictor of morbidity and mortality.
      The molecular mechanisms leading to skeletal muscle dysfunction/wasting are not
      fully understood and are likely to be multi-factorial. The need to develop
      therapeutic strategies aimed at improving skeletal muscle dysfunction/wasting
      requires a better understanding of the molecular mechanisms responsible for these
      abnormalities. Microarrays are powerful tools that allow the investigation of the
      expression of thousands of genes, virtually the whole genome, simultaneously. We
      aim at identifying genes and molecular pathways involved in skeletal muscle
      wasting in COPD. METHODS: We assessed and compared the vastus lateralis
      transcriptome of COPD patients with low fat free mass index (FFMI) as a surrogate
      of muscle mass (COPDL) (FEV1 30 +/- 3.6%pred, FFMI 15 +/- 0.2 Kg.m(-2)) with
      patients with COPD and normal FFMI (COPDN) (FEV1 44 +/- 5.8%pred, FFMI 19 +/- 0.5
      Kg.m(-2)) and a group of age and sex matched healthy controls (C) (FEV1 95 +/-
      3.9%pred, FFMI 20 +/- 0.8 Kg.m(-2)) using Agilent Human Whole Genome 4x44K
      microarrays. The altered expression of several of these genes was confirmed by
      real time TaqMan PCR. Protein levels of P21 were assessed by immunoblotting.
      RESULTS: A subset of 42 genes was differentially expressed in COPDL in comparison
      to both COPDN and C (PFP < 0.05; -1.5 >= FC >= 1.5). The altered expression of
      several of these genes was confirmed by real time TaqMan PCR and correlated with
      different functional and structural muscle parameters. Five of these genes
      (CDKN1A, GADD45A, PMP22, BEX2, CGREF1, CYR61), were associated with cell cycle
      arrest and growth regulation and had been previously identified in studies
      relating muscle wasting and ageing. Protein levels of CDKN1A, a recognized marker
      of premature ageing/cell cycle arrest, were also found to be increased in COPDL.
      CONCLUSIONS: This study provides evidence of differentially expressed genes in
      peripheral muscle in COPD patients corresponding to relevant biological processes
      associated with skeletal muscle wasting and provides potential targets for future
      therapeutic interventions to prevent loss of muscle function and mass in COPD.

PMID- 25567524
TI  - Differential profiles of direct and indirect modification of vector feeding
      behaviour by a plant virus.
AB  - Plant viruses interact with their insect vectors directly and indirectly via host
      plants, and this tripartite interaction may produce fitness benefits to both the
      vectors and the viruses. Our previous studies show that the Middle East-Asia
      Minor 1 (MEAM1) species of the whitefly Bemisia tabaci complex improved its
      performance on tobacco plants infected by the Tomato yellow leaf curl China virus
      (TYLCCNV), which it transmits, although virus infection of the whitefly per se
      reduced its performance. Here, we use electrical penetration graph recording to
      investigate the direct and indirect effects of TYLCCNV on the feeding behaviour
      of MEAM1. When feeding on either cotton, a non-host of TYLCCNV, or uninfected
      tobacco, a host of TYLCCNV, virus-infection of the whiteflies impeded their
      feeding. Interestingly, when viruliferous whiteflies fed on virus-infected
      tobacco, their feeding activities were no longer negatively affected; instead,
      the virus promoted whitefly behaviour related to rapid and effective sap
      ingestion. Our findings show differential profiles of direct and indirect
      modification of vector feeding behaviour by a plant virus, and help to unravel
      the behavioural mechanisms underlying a mutualistic relationship between an
      insect vector and a plant virus that also has features reminiscent of an insect
      pathogen. 

PMID- 25567525
TI  - Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations
      of Soluplus(r) and HPMCAS-HF.
AB  - The aim of this study was to evaluate a novel combination of Soluplus(r) and
      hypromellose acetate succinate (HPMCAS-HF) polymers for solubility enhancement as
      well as enhanced physicochemical stability of the produced amorphous solid
      dispersions. This was accomplished by converting the poorly water-soluble
      crystalline form of carbamazepine into a more soluble amorphous form within the
      polymeric blends. Carbamazepine (CBZ), a Biopharmaceutics Classification System
      class II active pharmaceutical ingredient (API) with multiple polymorphs, was
      utilized as a model drug. Hot-melt extrusion (HME) processing was used to prepare
      solid dispersions utilizing blends of polymers. Drug loading showed a significant
      effect on the dissolution rate of CBZ in all of the tested ratios of Soluplus(r)
      and HPMCAS-HF. CBZ was completely miscible in the polymeric blends of Soluplus(r)
      and HPMCAS-HF up to 40% drug loading. The extrudates were characterized by
      differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier
      transform infrared (FTIR) spectroscopy and dissolution studies. DSC and XRD data
      confirmed the formation of amorphous solid dispersions of CBZ in the polymeric
      blends of Soluplus(r) and HPMCAS-HF. Drug loading and release of CBZ was
      increased with Soluplus(r) (when used as the primary matrix polymer) when
      formulations contained Soluplus(r) with 7-21% (w/w) HPMCAS-HF. In addition, this
      blend of polymers was found to be physically and chemically stable at 40 degrees
      C, 75% RH over 12 months without any dissolution rate changes. 

PMID- 25567527
TI  - Electrochemical synthesis of small-sized red fluorescent graphene quantum dots as
      a bioimaging platform.
AB  - We report water-soluble, 3 nm uniform-sized graphene quantum dots (GQDs) with red
      emission prepared by electrochemical exfoliation of graphite in K2S2O8 solution.
      Such GQDs show a great potential as biological labels for cellular imaging. 

PMID- 25567526
TI  - Abeta reduction in BACE1 heterozygous null 5XFAD mice is associated with
      transgenic APP level.
AB  - BACKGROUND: The beta-secretase, BACE1, cleaves APP to initiate generation of the
      beta-amyloid peptide, Abeta, that comprises amyloid plaques in Alzheimer's
      disease (AD). Reducing BACE1 activity is an attractive therapeutic approach to
      AD, but complete inhibition of BACE1 could have mechanism-based side-effects as
      BACE1-/- mice show deficits in axon guidance, myelination, memory, and other
      neurological processes. Since BACE1+/- mice appear normal there is interest in
      determining whether 50% reduction in BACE1 is potentially effective in preventing
      or treating AD. APP transgenic mice heterozygous for BACE1 have decreased Abeta
      but the extent of reduction varies greatly from study to study. Here we assess
      the effects of 50% BACE1 reduction on the widely used 5XFAD mouse model of AD.
      RESULTS: 50% BACE1 reduction reduces Abeta42, plaques, and BACE1-cleaved APP
      fragments in female, but not in male, 5XFAD/BACE1+/- mice. 5XFAD/BACE1+/+ females
      have higher levels of Abeta42 and steady-state transgenic APP than males, likely
      caused by an estrogen response element in the transgene Thy-1 promoter. We
      hypothesize that higher transgenic APP level in female 5XFAD mice causes BACE1 to
      no longer be in excess over APP so that 50% BACE1 reduction has a significant
      Abeta42 lowering effect. In contrast, the lower APP level in 5XFAD males allows
      BACE1 to be in excess over APP even at 50% BACE1 reduction, preventing lowering
      of Abeta42 in 5XFAD/BACE1+/- males. We also developed and validated a dot blot
      assay with an Abeta42-selective antibody as an accurate and cost-effective
      alternative to ELISA for measuring cerebral Abeta42 levels. CONCLUSIONS: 50%
      BACE1 reduction lowers Abeta42 in female 5XFAD mice only, potentially because
      BACE1 is not in excess over APP in 5XFAD females with higher transgene
      expression, while BACE1 is in excess over APP in 5XFAD males with lower transgene
      expression. Our results suggest that greater than 50% BACE1 inhibition might be
      necessary to significantly lower Abeta, given that BACE1 is likely to be in
      excess over APP in the human brain. Additionally, in experiments using the 5XFAD
      mouse model, or other Thy-1 promoter transgenic mice, equal numbers of male and
      female mice should be used, in order to avoid artifactual gender-related
      differences.

PMID- 25567529
TI  - Integration of rigid and flexible organic parts for the construction of a
      homochiral metal-organic framework with high porosity.
AB  - Presented is a pair of homochiral metal-organic frameworks built from mixed
      ligands integrating rigid and flexible organic parts, and each compound shows
      high porosity and can be used for enantioselective separation of racemic 1
      phenethylalcohol and methyl lactate. 

PMID- 25567528
TI  - Emotion recognition in animated compared to human stimuli in adolescents with
      autism spectrum disorder.
AB  - There is equivocal evidence as to whether there is a deficit in recognising
      emotional expressions in Autism spectrum disorder (ASD). This study compared
      emotion recognition in ASD in three types of emotion expression media (still
      image, dynamic image, auditory) across human stimuli (e.g. photo of a human face)
      and animated stimuli (e.g. cartoon face). Participants were 37 adolescents (age
      11-16) with a diagnosis of ASD (33 male, 4 female). 42 males and 39 females
      served as typically developing, age-matched controls. Overall there was
      significant advantage for control groups over the ASD group for emotion
      recognition in human stimuli but not animated stimuli, across modalities. For
      static animated images specifically, those with ASD significantly outperformed
      controls. The findings are consistent with the ASD group using atypical explicit
      strategies. 

PMID- 25567530
TI  - Estradiol prevents Abeta 25 35-inhibited long-term potentiation induction through
      enhancing survival of newborn neurons in the dentate gyrus.
AB  - AIM AND METHODS: Estradiol (E2) is reported to attenuate beta-amyloid (Abeta)
      accumulation and slow the progression of Alzheimer's disease (AD). This study
      explored the beneficial effect of E2 in AD using histological examination and
      electrophysiological recording technique in AD model mice created by
      intracerebroventricular injection of beta-amyloid 25-35 (Abeta 25-35). RESULTS:
      Infusion of Abeta 25-35 reduced the number of newborn neurons in the 2nd week
      after birth, a critical period for neurite growth, and impaired high-frequency
      stimulation-dependent long-term potentiation (LTP) induction in perforant path
      granular synapses of hippocampal dentate gyrus (DG). Administration of E2 from
      the 2nd to 4th week after cell birth in Abeta 25-35-mice ameliorated the
      impairment of newborn neurons and LTP induction in DG. Acute application of E2
      failed to increase the newborn neurons and rescue LTP induction in the DG of
      Abeta 25-35-mice. CONCLUSIONS: The effect of E2 in Abeta 25-35-impaired LTP
      induction depends on its neuroprotection improvement.

PMID- 25567531
TI  - Enrichment of Human Stem-Like Prostate Cells with s-SHIP Promoter Activity
      Uncovers a Role in Stemness for the Long Noncoding RNA H19.
AB  - Understanding normal and cancer stem cells should provide insights into the
      origin of prostate cancer and their mechanisms of resistance to current treatment
      strategies. In this study, we isolated and characterized stem-like cells present
      in the immortalized human prostate cell line, RWPE-1. We used a reporter system
      with green fluorescent protein (GFP) driven by the promoter of s-SHIP (for stem
      SH2-domain-containing 5'-inositol phosphatase) whose stem cell-specific
      expression has been previously shown. We observed that s-SHIP-GFP-expressing RWPE
      1 cells showed stem cell characteristics such as increased expression of stem
      cell surface markers (CD44, CD166, TROP2) and pluripotency transcription factors
      (Oct4, Sox2), and enhanced sphere-forming capacity and resistance to arsenite
      induced cell death. Concomitant increased expression of the long noncoding RNA
      H19 was observed, which prompted us to investigate a putative role in stemness
      for this oncofetal gene. Targeted suppression of H19 with siRNA decreased Oct4
      and Sox2 gene expression and colony-forming potential in RWPE-1 cells.
      Conversely, overexpression of H19 significantly increased gene expression of
      these two transcription factors and the sphere-forming capacity of RWPE-1 cells.
      Analysis of H19 expression in various prostate and mammary human cell lines
      revealed similarities with Sox2 expression, suggesting that a functional
      relationship may exist between H19 and Sox2. Collectively, we provide the first
      evidence that s-SHIP-GFP promoter reporter offers a unique marker for the
      enrichment of human stem-like cell populations and highlight a role in stemness
      for the long noncoding RNA H19. 

PMID- 25567533
TI  - Sadism and Violent Reoffending in Sexual Offenders.
AB  - A diagnosis of sadism in sexual offenders is commonly regarded as indicative of
      high risk for violent reoffending. The purpose of the current two studies was to
      evaluate whether sadism is indeed associated with higher rates of violent
      (including sexual) reoffending. In Study 1 (meta-analysis), the rate of violent
      and sexual recidivism was assessed across seven samples of male sex offenders
      (total N = 2,169) as a function of diagnoses of sexual sadism. In Study 2 (N =
      768) the outcome (violent recidivism yes/no) was regressed on sadism, along with
      behavioral indicators of sexually sadistic offending, and scores from violence
      risk assessment instruments. In Study 1 (meta-analysis), the overall risk of
      sadists compared with nonsadists with respect to violent (including sexual
      contact) reoffending was slightly elevated (by a factor of 1.18), yet not
      significantly increased. Similarly, the risk of sexual reoffending among sadists
      was slightly, but not significantly, higher than among nonsadists (factor 1.38).
      According to Study 2, only a measure of sadistic behavior, not the clinical
      diagnosis, was associated with violent reoffending. This association, however,
      was not present once age and customary risk assessment instruments for violence
      risk were included in the regression. A clinical diagnosis of sexual sadism and
      behavioral measures of sadism are related to the risk of violent reoffending in
      sexual offenders. These associations, however, are weak and do not hold once
      variables relevant for the prediction of violence are controlled for. At the
      individual level, the risk for future violence in sadists can therefore be
      adequately described by customary risk assessment instruments. 

PMID- 25567534
TI  - Protective strengths, risk, and recidivism in a sample of known sexual offenders.
AB  - The relationship between protective strengths and risk, as assessed by the
      Inventory of Offender Risk, Needs, and Strengths, was examined with respect to
      the recidivism rate and type of reoffense in a sample of 110 adult males
      incarcerated for sexual offenses. The sample included offenders who were
      completing a prison-based sexual offense treatment program during the last 18
      months of their incarceration. Approximately 40% of the sample recidivated in
      some way, including 6% sexually, within the 6-year follow-up time. Self-perceived
      protective strengths were significantly valid predictors for sexual, violent, and
      general recidivism. In regression analyses, protective strengths accounted for a
      unique portion of the variance in sexual recidivism while controlling for overall
      risk. Consistent with research on the importance of protective strengths with
      other offender types, the continued study and inclusion of protective strengths
      in the assessment and treatment of sexual offenders is warranted. 

PMID- 25567532
TI  - The use of the Gail model, body mass index and SNPs to predict breast cancer
      among women with abnormal (BI-RADS 4) mammograms.
AB  - INTRODUCTION: Mammography screening results in a significant number of false
      positives. The use of pretest breast cancer risk factors to guide follow-up of
      abnormal mammograms could improve the positive predictive value of screening. We
      evaluated the use of the Gail model, body mass index (BMI), and genetic markers
      to predict cancer diagnosis among women with abnormal mammograms. We also
      examined the extent to which pretest risk factors could reclassify women without
      cancer below the biopsy threshold. METHODS: We recruited a prospective cohort of
      women referred for biopsy with abnormal (BI-RADS 4) mammograms according to the
      American College of Radiology's Breast Imaging-Reporting and Data System (BI
      RADS). Breast cancer risk factors were assessed prior to biopsy. A validated
      panel of 12 single-nucleotide polymorphisms (SNPs) associated with breast cancer
      were measured. Logistic regression was used to assess the association of Gail
      risk factors, BMI and SNPs with cancer diagnosis (invasive or ductal carcinoma in
      situ). Model discrimination was assessed using the area under the receiver
      operating characteristic curve, and calibration was assessed using the Hosmer
      Lemeshow goodness-of-fit test. The distribution of predicted probabilities of a
      cancer diagnosis were compared for women with or without breast cancer. RESULTS:
      In the multivariate model, age (odds ratio (OR)=1.05; 95% confidence interval
      (CI), 1.03 to 1.08; P<0.001), SNP panel relative risk (OR=2.30; 95% CI, 1.06 to
      4.99, P=0.035) and BMI (>=30 kg/m2 versus <25 kg/m(2); OR=2.20; 95% CI, 1.05 to
      4.58; P=0.036) were significantly associated with breast cancer diagnosis. Older
      women were more likely than younger women to be diagnosed with breast cancer. The
      SNP panel relative risk remained strongly associated with breast cancer diagnosis
      after multivariable adjustment. Higher BMI was also strongly associated with
      increased odds of a breast cancer diagnosis. Obese women (OR=2.20; 95% CI, 1.05
      to 4.58; P=0.036) had more than twice the odds of cancer diagnosis compared to
      women with a BMI<25 kg/m2. The SNP panel appeared to have predictive ability
      among both white and black women. CONCLUSIONS: Breast cancer risk factors,
      including BMI and genetic markers, are predictive of cancer diagnosis among women
      with BI-RADS 4 mammograms. Using pretest risk factors to guide follow-up of
      abnormal mammograms could reduce the burden of false-positive mammograms.

PMID- 25567535
TI  - TGF-beta1-siRNA delivery with nanoparticles inhibits peritoneal fibrosis.
AB  - Gene therapies may be promising for the treatment of peritoneal fibrosis (PF) in
      subjects undergoing peritoneal dialysis (PD). However, a method of delivery of
      treatment genes to the peritoneum is lacking. We attempted to develop an in vivo
      small interfering RNA (siRNA) delivery system with liposome-based nanoparticles
      (NPs) to the peritoneum to inhibit PF. Transforming growth factor (TGF)-beta1
      siRNAs encapsulated in NPs (TGF-beta1-siRNAs-NPs) dissolved in PD fluid were
      injected into the peritoneum of mice with PF three times a week for 2 weeks. TGF
      beta1-siRNAs-NPs knocked down TGF-beta1 expression significantly in the
      peritoneum and inhibited peritoneal thickening with fibrous changes. TGF-beta1
      siRNAs-NPs also inhibited the increase of expression of alpha-smooth muscle actin
      positive myofibroblasts. These results suggest that the TGF-beta1-siRNA delivery
      system with NPs described here could be an effective therapeutic option for PF in
      subjects undergoing PD. 

PMID- 25567536
TI  - Permanent acceptance of mouse cardiac allografts with CD40 siRNA to induce
      regulatory myeloid cells by use of a novel polysaccharide siRNA delivery system.
AB  - The CD40/CD154 co-stimulatory pathway is crucial in alloimmune response. We
      developed a novel small interfering RNA (siRNA) delivery system with a poly-dA
      extension at the 5'-end of the siRNA sense strand that was stably incorporated
      into 1,3-beta-glucan (schizophyllan, SPG). This was captured and incorporated
      into dendritic cells (DCs) through its receptor, Dectin-1, specifically silencing
      CD40 genes (siCD40) to exert immunoregulatory activity. siCD40/SPG-treated CBA
      mice permanently accepted B10 fully mismatched cardiac allografts. Consistent
      with graft survival, the infiltration of CD4(+), CD8(+) T cells into the graft
      was lower, and that the numbers of CD40(low)CD11c(+) DCs cells and
      CD4(+)Foxp3(+)cells were increased in both the graft and in the recipient spleen.
      In addition, naive CBA recipients given an adoptive transfer of splenocytes from
      the primary recipients with siCD40/SPG accepted a heart graft from donor-type
      B10, but not third-party Balb/c mice. In conclusion, the treatment with
      siCD40/SPG targeting DCs could generate antigen-specific Tregs, resulting in the
      permanent acceptance of mouse cardiac allografts. These findings have important
      implications for clarifying the mechanism underlying the induction of tolerance
      in DCs, and also highlight the potential of immunomodulation and the feasibility
      of siRNA-based clinical therapy in the transplantation field. 

PMID- 25567539
TI  - Erratum: Machine learning methods in the computational biology of cancer.
AB  - [This corrects the article DOI: 10.1098/rspa.2014.0081.].

PMID- 25567537
TI  - Vpx-containing dendritic cell vaccine induces CTLs and reactivates latent HIV-1
      in vitro.
AB  - Eradication of human immunodeficiency virus-1 (HIV-1) from an infected individual
      requires a means of inducing production of virus from latently infected cells and
      stimulating an immune response against the infected cells. We report the
      development of lentiviral vectors that transduce dendritic cells (DCs) to both
      induce production of virus from latently infected cells and stimulate antigen
      specific cytotoxic T lymphocytes (CTLs). The vectors package Vpx, a lentiviral
      accessory protein that counteracts the SAMHD1-mediated block to DC transduction,
      allowing for long-term expression of vector-encoded proteins. The vectors encode
      influenza or HIV-1-derived epitopes fused via a self-cleaving peptide to CD40L
      that releases the peptide into the endoplasmic reticulum for entry into the
      antigen presentation pathway. Expression of CD40L caused transduced DCs to mature
      and produce Th1-skewing cytokines. The DCs presented antigen to CD8 T cells,
      enhancing antigen-specific CTLs. Coculture of the transduced DCs with latently
      infected cells induced high-level virus production, an effect that was mediated
      by tumor necrosis factor alpha. The ability of a DC vaccine to reactivate latent
      HIV-1 and stimulate an adaptive immune response provide a means to reduce the
      size of the latent reservoir in patients. This strategy can also be applied to
      develop DC vaccines for other diseases. 

PMID- 25567540
TI  - Lactobacillus-produced exopolysaccharides and their potential health benefits: a
      review.
AB  - Lactic acid bacteria, such as those of the Lactobacillus genus, naturally reside
      within the microbiota of the human body and have long been used as starter
      cultures and probiotic enhancers in fermented foods, such as fermented drinks,
      yoghurts and cheeses. Many of the beneficial qualities of these bacteria have
      traditionally been associated with the bacteria themselves, however, a recent
      spate of studies have demonstrated a wide variety of biological effects exhibited
      by lactobacilli-produced exopolysaccharides which could, theoretically, confer a
      range of local and systemic health benefits upon the host. In this review, we
      discuss the production of exopolysaccharides within the Lactobacillus genus and
      explore their potential as beneficial bioactive compounds. 

PMID- 25567538
TI  - Enhancing the bystander killing effect of an oncolytic HSV by arming it with a
      secretable apoptosis activator.
AB  - Although oncolytic viruses have shown great promise as cancer therapeutics,
      results from a recent phase III clinical trial indicate that their potency may
      need further improvement for a clear clinical benefit. Here, we report a novel
      strategy to increase the bystander effect of virotherapy by arming an oncolytic
      virus with a secreted form of a Her2 single chain antibody linked to a self
      multimerizing Fas ligand extracellular domain (Her2-COL-sFasL). The rationale is
      that, due to its much smaller size, this apoptosis activator can overcome
      obstacles such as the dense collagen in the tumor tissues to spread more freely
      than the viral particles. When measured in vitro, Her2-COL-sFasL was found to
      efficiently induce caspase cleavage, resulting in an 80% reduction in cell
      viability. Once incorporated into the genome of an oncolytic type 2 herpes
      simplex virus, FusOn-H3, Her2-COL-sFasL potentiates the therapeutic efficacy of
      the virus in an aggressive syngeneic mammary tumor model. Our data suggest that
      arming an oncolytic virus with a secretable and self-multimerizing apoptosis
      inducer is a feasible strategy to improve the potency of virotherapy. 

PMID- 25567541
TI  - Different intraoperative kinematics with comparable clinical outcomes of
      ultracongruent and posterior stabilized mobile-bearing total knee arthroplasty.
AB  - PURPOSE: There remains no consensus as to whether mobile total knee arthroplasty
      (TKA) should use a posterior cruciate ligament-sacrificing ultracongruent (UC) or
      a posterior cruciate ligament-substituting posterior stabilized (PS) prosthesis.
      The purpose of this study was to assess intraoperative kinematics and clinical
      outcomes of UC and PS rotating platform mobile-bearing TKA. METHODS: In this
      randomized controlled study, mobile UC TKA prostheses (n = 45) were compared with
      mobile PS TKA prostheses (n = 45) with regard to intraoperative kinematics and
      clinical outcomes. The passive kinematic study using intraoperative navigation
      system included anterior/posterior translation, varus/valgus alignment and
      rotation of femur during flexion. The patients were clinically and
      radiographically evaluated over a 3-year follow-up. RESULTS: Paradoxical anterior
      translation of the femur was 10.8 +/- 5.2 mm in the UC knee from 0 degrees  to 82
      degrees  of knee flexion and 8.7 +/- 3.0 mm in the PS knee from 0 degrees  to 70
      degrees  of knee flexion (p = 0.027). Paradoxical internal rotation of the femur
      was 5.8 degrees  in the UC knees and 9.9 degrees  in the PS knees (p = 0.003).
      But, there was no significant difference between the groups in regard to the
      coronal alignment. There was no significant difference in the range of motion, KS
      knee scores, KS function scores, and WOMAC index scores. CONCLUSIONS: Despite
      different intraoperative kinematics between mobile UC and mobile PS TKA, neither
      design reproduced physiologic knee kinematics and there was no difference in
      clinical outcomes between the two groups. The clinical relevance of the study is
      that despite different intraoperative kinematics, UC design can be a considerable
      alternative to PS design in mobile-bearing TKA in respect of clinical outcomes.
      LEVEL OF EVIDENCE: II.

PMID- 25567542
TI  - Results of an open posterior bone block procedure for recurrent posterior
      shoulder instability after a short- and long-time follow-up.
AB  - PURPOSE: The aim of the present study was to analyse and compare the clinical and
      radiological results after open posterior bone block procedure at long- (LT) and
      short-term (ST) follow-up. The hypothesis was that placement of a bone block at
      the posterior glenoid rim in a technique of extending the glenoid surface will
      create permanent joint stability even in cases with hyperlaxity without a
      clinically relevant loss of motion or increase in osteoarthritis. METHODS:
      Fifteen consecutive shoulders with recurrent posterior dislocation were evaluated
      clinically and radiologically. The Rowe score, Western Ontario Shoulder Index,
      Walch-Duplay score and the Constant-Murley score were used for clinical
      evaluation. The patients were categorized according to their follow-up period as
      either ST follow-up (min 12 months) or LT follow-up (min 42 months). RESULTS: The
      clinical results showed no significant difference between ST (9) and LT (6) with
      good to very good overall results in the subjective as well as the objective
      scores (CS, RS, WDS). At LT, most patients felt mild to minor pain under strain.
      The difference in pain between the groups was not significant. Active ranges of
      motion and strength assessments were normal in all cases. In one case, recurrent
      dislocations occurred after bone graft resorption 6 months post-operatively. Only
      one patient presented mild osteoarthritis, without further progress at follow-up.
      CONCLUSION: The open posterior bone block procedure can be a successful treatment
      option for recurrent posterior shoulder instability at ST and LT follow-up. This
      series showed a low rate of recurrent dislocations without development or
      progression of osteoarthritis. Since soft tissue procedures do not always provide
      satisfying results, the posterior bone block augmentation presents a reliable
      technique for the treatment of symptomatic posterior instability. LEVEL OF
      EVIDENCE: Case Series, Treatment Study, Level IV.

PMID- 25567544
TI  - Switchable platinum-based tweezers with Pt-Pt bonding and selective luminescence
      quenching.
AB  - Molecular tweezers incorporating peripheral platinum salphen complexes and a
      central chelating terpyridine group have been synthesized. The terpyridine can be
      switched upon metal binding between a free 'W' shaped form and a coordinated 'U'
      form. The crystallographic structure of the zinc-closed molecular tweezers was
      obtained and presented a strong pi-stacking between the Pt-salphen units
      associated with a Pt-Pt bond. The luminescence properties, notably in response to
      selected guest ions (Zn(2+), Pb(2+), Hg(2+)) and the resulting mechanical motion,
      have been investigated by UV-Vis and emission spectroscopy. While ion
      coordination to the terpy resulted in no significant changes in the luminescence,
      a selective intercalation of a second Hg(2+) associated with a large differential
      quenching was observed. 

PMID- 25567543
TI  - Heterogeneity in individually experienced temperatures (IETs) within an urban
      neighborhood: insights from a new approach to measuring heat exposure.
AB  - Urban environmental health hazards, including exposure to extreme heat, have
      become increasingly important to understand in light of ongoing climate change
      and urbanization. In cities, neighborhoods are often considered a homogenous and
      appropriate unit with which to assess heat risk. This manuscript presents results
      from a pilot study examining the variability of individually experienced
      temperatures (IETs) within a single urban neighborhood. In July 2013, 23 research
      participants were recruited from the South End neighborhood of Boston and
      equipped with Thermochron iButtons that measured the air temperatures surrounding
      individuals as they went about their daily lives. IETs were measured during a
      heat wave period (July 17-20), which included 2 days with excessive heat warnings
      and 1 day with a heat advisory, as well as a reference period (July 20-23) in
      which temperatures were below seasonal averages. IETs were not homogeneous during
      the heat wave period; mean IETs were significantly different between participants
      (p < 0.001). The majority of participants recorded IETs significantly lower than
      outdoor ambient temperatures (OATs), and on average, the mean IET was 3.7 
      degrees C below the mean OAT. Compared with IETs during the reference period,
      IETs during the heat wave period were 1.0  degrees C higher. More than half of
      participants did not experience statistically different temperatures between the
      two test periods, despite the fact that the mean OAT was 6.5  degrees C higher
      during the heat wave period. The IET data collected for this sample and study
      period suggest that (1) heterogeneity in individual heat exposure exists within
      this neighborhood and that (2) outdoor temperatures misrepresent the mean
      experienced temperatures during a heat wave period. Individual differences in
      attributes (gender, race, socioeconomic status, etc.), behaviors (schedules,
      preferences, lifestyle, etc.), and access to resources are overlooked
      determinants of heat exposure and should be better integrated with group- and
      neighborhood-level characteristics. Understanding IETs for the population at
      large may lead to innovative advances in heat-health intervention and mitigation
      strategies.

PMID- 25567545
TI  - Acoustic simulation of a patient's obstructed airway.
AB  - This research focuses on the numerical simulation of stridor; a high pitched,
      abnormal noise, resulting from turbulent airflow and vibrating tissue through a
      partially obstructed airway. Characteristics of stridor noise are used by medical
      doctors as indication for location and size of the obstruction. The relation
      between type of stridor and the various diseases associated with airway
      obstruction is unclear; therefore, simply listening to stridor is an unreliable
      diagnostic tool. The overall aim of the study is to better understand the
      relationship between characteristics of stridor noise and localization and size
      of the obstruction. Acoustic analysis of stridor may then in future simplify the
      diagnostic process, and reduce the need for more invasive procedures such as
      laryngoscopy under general anesthesia. In this paper, the feasibility of a
      coupled flow, acoustic and structural model is investigated to predict the noise
      generated by the obstruction as well as the propagation of the noise through the
      airways, taking into account a one-way coupled fluid, structure, and acoustic
      interaction components. The flow and acoustic solver are validated on a diaphragm
      and a simplified airway model. A realistic airway model of a patient suffering
      from a subglottic stenosis, derived from a real computed tomography scan, is
      further analyzed. Near the mouth, the broadband noise levels at higher
      frequencies increased with approximately 15-20 dB comparing the stridorous model
      with the healthy model, indicating stridorous sound.

PMID- 25567546
TI  - Readiness to reconcile and post-traumatic distress in German survivors of wartime
      rapes in 1945.
AB  - BACKGROUND: Sexual violence and wartime rapes are prevalent crimes in violent
      conflicts all over the world. Processes of reconciliation are growing challenges
      in post-conflict settings. Despite this, so far few studies have examined the
      psychological consequences and their mediating factors. Our study aimed at
      investigating the degree of longtime readiness to reconcile and its associations
      with post-traumatic distress within a sample of German women who experienced
      wartime rapes in 1945. METHODS: A total of 23 wartime rape survivors were
      compared to age- and gender-matched controls with WWII-related non-sexual
      traumatic experiences. Readiness to reconcile was assessed with the Readiness to
      Reconcile Inventory (RRI-13). The German version of the Post-traumatic Diagnostic
      Scale (PDS) was used to assess post-traumatic stress disorder (PTSD)
      symptomatology. RESULTS: Readiness to reconcile in wartime rape survivors was
      higher in those women who reported less post-traumatic distress, whereas the
      subscale "openness to interaction" showed the strongest association with post
      traumatic symptomatology. Moreover, wartime rape survivors reported fewer
      feelings of revenge than women who experienced other traumatization in WWII.
      CONCLUSIONS: Our results are in line with previous research, indicating that
      readiness to reconcile impacts healing processes in the context of conflict
      related traumatic experiences. Based on the long-lasting post-traumatic
      symptomatology we observed that our findings highlight the need for psychological
      treatment of wartime rape survivors worldwide, whereas future research should
      continue focusing on reconciliation within the therapeutic process.

PMID- 25567547
TI  - Anxiety related to dental care in children and adolescents in a low-income
      Brazilian community.
AB  - AIM: The aims of this study were to determine the prevalence of anxiety related
      to dental care and analyse associated factors in children and adolescents in a
      low-income community in Recife, Brazil. STUDY DESIGN: A cross-sectional study was
      conducted with 101 children and adolescents from both genders, aged from 6 to 16
      years. METHODS: The dependent variable, anxiety related to dental care, was
      obtained by the dental anxiety questionnaire (DAQ). The independent variables
      were: the previous experience, the pain history and DMFT-dmft. STATISTICS: Chi
      square test was performed to analyse the associations. In the multivariate
      analysis, binary logistic regression was performed. RESULTS: The probability of
      females in the sample experiencing anxiety was 3.1 times higher compared to males
      (OR 3.1 [1.3-7.2]). Children and adolescents who had never visited a dentist
      showed a level of anxiety 5.6 times higher than those who did (OR 5.6 [1.3
      22.7]). CONCLUSIONS: Anxiety related to the dental care presented a prevalence of
      36.6 % in a population aged 6-16 years. Females in this group, as well as
      subjects who had never been to the dentist were more likely to present anxiety.

PMID- 25567548
TI  - Intractable hiccup and vomiting, neuropathic pruritus and tonic spasms in a case
      of neuromyelitis optica spectrum disorder.

PMID- 25567549
TI  - Application of the APACHE II score to assess the condition of patients with
      critical neurological diseases.
AB  - The Acute Physiology And Chronic Health Evaluation II (APACHE II) scoring system
      has been commonly used to assess the severity of patients' diseases in general
      intensive care units (ICUs). However, few studies have investigated the
      application of this scoring system in patients in neurologic ICUs. In this study,
      the APACHE II scores of 102 patients in the neurologic ICU were calculated within
      the first 24 h. The actual mortality and predicted mortality were obtained based
      on these scores and analyzed statistically. The data indicated that cerebral
      hemorrhage, cerebral infarction and intracranial infection accounted for the top
      three causes for admission to the neurologic ICU, and these conditions were
      associated with high APACHE II scores and high predicted mortality. Additionally,
      the actual mortality rate was lower than the predicted rate after effective
      treatment. All patients were divided into groups according to their APACHE II
      scores, and we found that higher APACHE II scores were associated with higher
      actual mortality, especially for patients whose APACHE II scores were greater
      than 10. The APACHE II scores of the deceased patient group were higher than
      those of the surviving group, and this difference was statistically significant.
      In conclusion, our study found that the APACHE II scoring system may provide
      valuable information for predicting patient's condition and prognosis in
      neurologic ICUs.

PMID- 25567550
TI  - Axonal regeneration inhibitors: emerging therapeutic options.
AB  - For the most part, the central nervous system is unable to regenerate. The
      majority of injuries of vascular, inflammatory, degenerative and traumatic
      aetiology lead to an irreversible loss of central nervous system function. The
      paper presents the role of Nogo-A, MAG and OMgp proteins in the inhibition of
      central nervous system regeneration, and their potential clinical significance.

PMID- 25567551
TI  - Phase behavior of electrostatically complexed polyelectrolyte gels using an
      embedded fluctuation model.
AB  - Nanostructured, responsive hydrogels formed due to electrostatic interactions
      have promise for applications such as drug delivery and tissue mimics. These
      physically cross-linked hydrogels are composed of an aqueous solution of
      oppositely charged triblocks with charged end-blocks and neutral, hydrophilic mid
      blocks. Due to their electrostatic interactions, the end-blocks microphase
      separate and form physical cross-links that are bridged by the mid-blocks. The
      structure of this system was determined using a new, efficient embedded
      fluctuation (EF) model in conjunction with self-consistent field theory. The
      calculations using the EF model were validated against unapproximated field
      theoretic simulations with complex Langevin sampling and were found consistent
      with small angle X-ray scattering (SAXS) measurements on an experimental system.
      Using both the EF model and SAXS, phase diagrams were generated as a function of
      end-block fraction and polymer concentration. Several structures were observed
      including a body-centered cubic sphere phase, a hexagonally packed cylinder
      phase, and a lamellar phase. Finally, the EF model was used to explore how
      parameters that directly relate to polymer chemistry can be tuned to modify the
      resulting phase diagram, which is of practical interest for the development of
      new hydrogels. 

PMID- 25567552
TI  - Neural oscillations as a translational tool in schizophrenia research: rationale,
      paradigms and challenges.
AB  - Neural oscillations have received recently a great deal of interest in
      schizophrenia research because of the possibility to integrate findings from non
      invasive electro/magnetoencephalographical recordings with pre-clinical research,
      which could potentially lead to the identification of pathophysiological
      mechanisms and novel treatment targets. In the current paper, we review the
      potential as well as the challenges of this approach by summarizing findings on
      alterations in rhythmic activity from both animal models and human data which
      have implicated dysfunctional neural oscillations in the explanation of cognitive
      deficits and certain clinical symptoms of schizophrenia. Specifically, we will
      focus on findings that have examined neural oscillations during 1) perceptual
      processing, 2) working memory and executive processes and 3) spontaneous
      activity. The importance of the development of paradigms suitable for human and
      animal models is discussed as well as the search for mechanistic explanation for
      oscillatory dysfunctions. 

PMID- 25567553
TI  - Dementia praecox redux: a systematic review of the nicotinic receptor as a target
      for cognitive symptoms of schizophrenia.
AB  - Most individuals with schizophrenia suffer some cognitive dysfunction: such
      deficits are predictive of longer-term functioning; and current dopamine-blocking
      antipsychotics have made little impact on this domain. There is a pressing need
      to develop novel pharmacological agents to tackle this insidious but most
      disabling of problems. The acetylcholinergic system is involved in cognitive and
      attentional processing, and its metabotropic and nicotinic receptors are
      widespread throughout the brain. Deficits in acetylcholinergic functioning occur
      in schizophrenia, and high rates of tobacco smoking have been posited to
      represent a form of self-medication. The nicotinic acetylcholine receptor (nAChR)
      has emerged as a putative target to improve cognitive deficits in schizophrenia,
      and this study systematically reviewed the emerging data. Nineteen studies were
      identified, covering three compound classes: agonists at the alpha7 and alpha
      4beta2 nAChRs, and positive allosteric modulators. Overall data are
      underwhelming: some studies showed significant improvements in cognition but as
      many studies had negative findings. It remains unclear if this represents drug
      limitations or nascent study methodology problems. The literature is particularly
      hindered by variability in inclusion of smokers, generally small sample sizes,
      and a lack of consensus on cognitive test batteries. Future work should evaluate
      longer-term outcomes, and, particularly, the effects of concomitant cognitive
      training. 

PMID- 25567554
TI  - Functional brain connectivity phenotypes for schizophrenia drug discovery.
AB  - While our knowledge of the pathophysiology of schizophrenia has increased
      dramatically, this has not translated into the development of new and improved
      drugs to treat this disorder. Human brain imaging and electrophysiological
      studies have provided dramatic new insight into the mechanisms of brain
      dysfunction in the disease, with a swathe of recent studies highlighting the
      differences in functional brain network and neural system connectivity present in
      the disorder. Only recently has the value of applying these approaches in
      preclinical rodent models relevant to the disorder started to be recognised. Here
      we highlight recent findings of altered functional brain connectivity in
      preclinical rodent models and consider their relevance to those alterations seen
      in the brains of schizophrenia patients. Furthermore, we highlight the potential
      translational value of using the paradigm of functional brain connectivity
      phenotypes in the context of preclinical schizophrenia drug discovery, as a means
      both to understand the mechanisms of brain dysfunction in the disorder and to
      reduce the current high attrition rate in schizophrenia drug discovery. 

PMID- 25567556
TI  - Immigration, ethnicity, and avoidable mortality in Canada, 1991-2006.
AB  - OBJECTIVE: Avoidable mortality is a well-recognized, but less studied indicator
      of the performance of the health system. First, the study seeks to establish
      whether immigrants overall and selected foreign-born ethnic groups (Western
      Europeans, South Asians, Chinese, and Filipinos) have an advantage over
      nonimmigrants in avoidable mortality. Second, it assesses the effect of
      sociodemographic and socioeconomic factors on any observed differences by
      duration of residence. DESIGN: Deaths grouped by cause of death and by behavioral
      risk factors, namely smoking-related and alcohol-related, were derived from the
      1991 Canadian Census Cohort: Mortality and Cancer Follow-up. The analysis
      estimated age-standardized mortality rates (ASMRs), rate ratios, and rate
      differences and also fitted hazard regression models for the overall Canadian
      born population and for selected foreign-born ethnicities by sex. Predictors were
      assessed at baseline. RESULTS: Compared to the Canadian-born persons, foreign
      born men and women had lower ASMRs for overall avoidable mortality and also for
      selected causes of avoidable mortality. The only exception to this overall trend
      was for ischemic heart disease among South Asian women. Except for the order of
      prominence, the three leading causes of death for nonimmigrant and immigrant men
      and women overall were ischemic heart diseases, smoking-related diseases, and
      neoplasms. A similar pattern was observed among the ethnic groups, except for
      circulatory heart diseases replacing ischemic heart diseases and smoking-related
      diseases among Chinese and Filipino women, respectively. In the hazard regression
      analysis, the risk of avoidable mortality was lower for immigrants overall and
      selected ethnicities irrespective of the duration in Canada compared to
      nonimmigrants. These differences persisted even with adjustment for
      sociodemographic and socioeconomic factors. CONCLUSION: Immigrants overall and
      the selected ethnicities enjoy an advantage over nonimmigrants in avoidable
      mortality. However, for certain causes of death especially ischemic heart disease
      mortality among South Asian women, immigrants appeared worse-off than
      nonimmigrants. The results suggest differential access to and use of health
      services, differences in protective health-related behavior, and the healthy
      immigrant effect.

PMID- 25567557
TI  - Recurrent fetal complex ovarian cysts with rupture followed by simple cyst in the
      neonatal period with no adverse sequelae.
AB  - Fetal ovarian cysts are the most frequent type of abdominal tumors in female
      fetuses with prenatal detection rate of more than 30%. The etiology of fetal
      ovarian cysts is unclear, but hormonal stimulation as well as presence of
      maternal diabetes, hypothyroidism, Rh iso-immune hemolytic disease and toxemia
      has been generally considered responsible for the disease. Complications of fetal
      ovarian cysts include compression of other viscera, cyst rupture, hemorrhage and,
      most frequently, ovarian torsion with consequent loss of the ovary. Management is
      controversial with several options described in the literature, including
      watchful expectancy, antenatal aspiration of simple cysts to prevent torsion and
      ovarian loss and finally, resection of all complex cysts in the neonatal period.
      To date, no case report has described recurrent complex cysts with rupture in the
      fetal period and recurrence of simple cyst in neonatal period. By presenting this
      case, we wanted to show that surgical intervention in case of prenatally
      diagnosed fetal ovarian cyst should be considered postnatally and only in
      symptomatic or complicated cases. 

PMID- 25567558
TI  - Wound morbidity with staples compared with suture for cesarean skin closure by
      diabetic status.
AB  - OBJECTIVE: To determine if the risk of post-cesarean wound morbidity in patients
      undergoing staple versus suture closure is modified by diabetic status. METHODS:
      Secondary analysis of a randomized trial of skin closure with subcuticular 4-0
      monocryl suture or surgical staples after cesarean delivery. The primary outcome
      was a composite of wound disruption or infection within 4-6 weeks. We compared
      the association between this outcome and skin closure method by diabetic status
      (also stratified by gestational or pregestational) using the Breslow-Day test for
      interaction. RESULTS: Of 350 patients, 179 were randomized to staples and 171 to
      suture. Of the 67 (19.1%) diabetic patients, 35 were gestational and 32
      pregestational. The incidence of composite wound morbidity in non-diabetics was
      16.7% for staples and 3.6% for suture (p <= 0.001, RR: 4.6, 95% CI: 1.8-11.8); it
      was 5.7% for staples and 15.6% for sutures in diabetics (p = 0.25, RR: 0.4, 95%
      CI: 0.1-1.7). The corresponding Breslow-Day p value indicated a significant
      difference between diabetics and non-diabetics (p = 0.002). Stratified further by
      gestational and pregestational diabetes, the RRs were 0.3 (95% CI: 0.03-2.4) and
      0.5 (95% CI: 0.05-5.0) compared to non-diabetics, respectively. Each diabetic sub
      group was significantly different from non-diabetics (Breslow-Day p values for
      homogeneity p = 0.005 and p = 0.045, respectively). CONCLUSIONS: The use of
      staples compared with subcuticular suture for cesarean skin closure is associated
      with increased wound morbidity. While this is true for non-diabetics, further
      studies of diabetics are needed to evaluate for a null or opposite effect of
      closure type.

PMID- 25567555
TI  - Guanfacine enhances inhibitory control and attentional shifting in early
      abstinent cocaine-dependent individuals.
AB  - OBJECTIVES: Attenuation of adrenergic drive and cognitive enhancement, via
      stimulation of alpha2 pre- and post-synaptic receptors, may selectively enhance
      executive performance in early abstinent cocaine-dependent individuals. As these
      cognitive processes underpin important treatment-related behaviors, the alpha2
      agonist, guanfacine HCl, may represent an effective pharmaco-therapeutic
      intervention. METHODS: Twenty-five early abstinent cocaine-dependent individuals
      were administered a battery of neurocognitive tasks on entry into treatment
      (baseline) and again following 3 weeks of either placebo or guanfacine treatment
      (up to 3 mg). Tasks included: Stop Signal, Stroop, 3-Dimentional Intra
      dimensional/Extra-dimensional (IDED) task, Spatial Working Memory (SWM), Paired
      Associates Learning (PAL), Verbal Fluency and the Rey Auditory Verbal Learning
      Test (RAVLT). RESULTS: Compared with placebo, the guanfacine group demonstrated
      attenuated anxiety and negative affect as well as improved performance on
      selective executive tests. This included fewer directional errors on the stop
      signal task, fewer errors on the extra-dimensional shift component of the IDED
      task and better attentional switching during verbal fluency. Guanfacine did not
      improve strategic working memory or peripheral memory. CONCLUSION: Guanfacine
      improves selective cognitive processes which may underlie salient treatment
      related regulatory behaviors. Alpha2 agonists may therefore represent important
      agents for cocaine dependence.

PMID- 25567559
TI  - Effects of transcutaneous electrical nerve stimulation on fetal and placental
      development in an experimental model of placental insufficiency.
AB  - OBJECTIVE: To elucidate the effects of transcutaneous electrical nerve
      stimulation (TENS) in pregnancies with placental insufficiency. METHODS: Pregnant
      rats were subjected to uterine artery ligation and to TENS according to the
      following groups: ligated stimulated (LS); ligated non-stimulated (LN), control
      stimulated (CS); and control non-stimulated (CN). Fetal external measurements,
      such as crown-rump length (CRL), fronto-occipital distance (FOD), thoracic
      ventral-dorsal (TVDD) and abdominal ventral-dorsal (AVDD) distances were analyzed
      together with the area occupied by fetal internal organs. Glucose transporter 1
      (GLUT-1) expression was evaluated by immunohistochemistry in fetal organs.
      Thickness of junctional, labyrinth and intermediate placental zones was analyzed
      by morphometric evaluation in HE-stained slides, and placental hypoxia-inducible
      factor 1 alfa expression was measured by real-time polymerase chain reaction.
      RESULTS: In LN and CS groups compared to the CN group, CRL was reduced
      (27.51/28.95 versus 30.16 mm), as well as FOD (6.63/6.63 versus 7.36 mm), AVDD
      (7.38/8.00 versus 8.61 mm) and TVDD (6.46/6.87 versus 7.23 mm). Brain GLUT-1
      expression was higher in LS (1.3%) and CS (1.8%). The area occupied by placental
      vessels in the labyrinth zone (29.67 +/- 3.51 versus 20.83 +/- 7.63) and
      intermediate zone (26.46 +/- 10.21 versus 10.86 +/- 8.94) was larger in the LS
      group than in the LN group. CONCLUSIONS: Our results suggest a negative effect of
      TENS on placental development, thus compromising the maintenance of adequate
      blood flow to the fetus.

PMID- 25567561
TI  - Tenascin C levels in patients with mild and severe preeclampsia.
AB  - OBJECTIVE: To determine the serum tenascin-C (TN-C) levels in cases with mild and
      severe preeclampsia. METHODS: Pregnant women were divided into three groups,
      namely healthy pregnants (Group 1, n = 20), pregnants with mild preeclampsia
      (Group 2, n = 20) and pregnants with severe preeclampsia (Group 3, n = 20). The
      groups were formed so as to match each other in terms of gestational week. From
      each pregnant woman, pre- and post-delivery blood samples were obtained to
      measure serum TN-C levels. The data were evaluated using the Kruskall-Wallis
      variance analysis. For the obtained values of p < 0.05, the groups were compared
      in pairs. A p value of < 0.017 was accepted as significant. RESULTS: In Groups 1,
      2 and 3, the prepartum TN-C levels were 5.02 +/- 0.4 ug/ml, 12.8 +/- 2.9 ug/ml
      and 33.8 +/- 11.7 ug/ml, and in the postpartum TN-C levels were 4.7 +/- 0.1
      ug/ml, 11.7 +/- 1.8 ug/ml and 50.6 +/- 33.8 ug/ml, respectively. There was a
      significant difference between the groups in terms of the prepartum and
      postpartum TN-C levels (p < 0.017, Mann-Whitney U [MWU] test). There was also a
      significant difference in the prepartum TN-C levels between Groups 2 and 3 (p <
      0.017, MWU test). CONCLUSIONS: The prepartum and postpartum TN-C levels were
      significantly higher in mild and severe preeclampsia than those in healthy
      pregnants.

PMID- 25567560
TI  - Nature and nurture in the development of childhood obesity: early infant feeding
      practices of overweight/obese mothers differ compared to mothers of normal body
      mass index.
AB  - OBJECTIVE: The purpose of this study was to describe early infant feeding
      practices among overweight/obese mothers using the Infant Feeding Practices Study
      II (IFPS II). METHODS: In this study, we used data pertaining to the first 2
      months postpartum of IFPS II. The data set includes 2387 mothers who provided
      information about infant feeding habits at the 2-month postpartum period.
      RESULTS: Overweight/obese mothers were less likely to breastfeed exclusively at 2
      months infant age and more likely to breastfeed at low intensity the first 2
      months compared to mothers of normal body mass index (BMI). Logistic regression
      analysis revealed, that after controlling for potential confounders, obese
      mothers were 1.38 (95% CI: 1.11, 1.72) times more likely to introduce solids to
      their infants before 4 months of age, and 1.37 (95% CI: 1.10, 1.89) times more
      likely to add cereal to the infant formula than their normal BMI counterparts.
      CONCLUSIONS: In conclusion, overweight/obese mothers not only fall short of
      clinical practice guidelines in regards to breastfeeding, but also are more
      likely to initiate early introduction (<4 months infant age) to solid foods
      compared to their normal BMI counterparts. Interventions should be targeted to
      this group.

PMID- 25567562
TI  - Risk factor profile of massive pulmonary haemorrhage in neonates: the impact on
      survival studied in a tertiary care centre.
AB  - OBJECTIVE: Pulmonary haemorrhage (PH) in neonates is a fatal event leading to
      hazardous complications and even death. The aim of this study was to elucidate
      influential factors of the ultimate disease course that affect death or survival.
      METHODS: Infants treated for PH in our institution from March 2009 to December
      2013 were retrospectively reviewed. Infants transferred from other hospitals were
      excluded. Infants were grouped into two categories, deceased or survived at
      neonatal intensive care unit discharge. Information regarding perinatal history,
      initial management and laboratory results were obtained and analysed for each
      group. RESULTS: Seventy infants fulfilled the inclusion criteria, 41 infants in
      the deceased group and 29 infants in the survived group. Overall, the infants in
      the deceased group displayed lower gestational age (27 and 1/7 +/- 3.610 versus
      29 and 3/7 +/- 3.530 weeks, p = 0.009) and lower one-minute (2.342 +/- 1.493
      versus 4.035 +/- 2.079, p < 0.001) and five-minute Apgar scores (2.342 +/- 1.493
      versus 4.035 +/- 2.079, p < 0.001) and required aggressive resuscitation (p =
      0.003) and a greater number of inotropes (2.195 +/- 1.346 versus 1.069 +/- 0.704,
      p < 0.001). Deceased infants were administered increased amounts of fluid during
      the first 24 h after birth (117.783 +/- 32.325 versus 99.379 +/- 17.728 mL/kg, p
      = 0.004). A relatively short prothrombin time impacted survival (p = 0.01),
      whereas platelet count was the only factor that significantly affected the time
      length from the onset of PH to death (p = 0.01). CONCLUSION: Infants with a lower
      gestational age in a compromised state are prone to die once PH develops. The
      initial management of fluid intake not to exceed the adequate limit is especially
      important in order to prevent PH-related deaths when correcting hypoalbuminemia
      and coagulopathy.

PMID- 25567563
TI  - Impact of chorioamnionitis on short- and long-term outcomes in very low birth
      weight preterm infants: the Neonatal Research Network Japan.
AB  - OBJECTIVE: To evaluate the short- and long-term outcomes among very low birth
      weight (VLBW) preterm infants after histologic chorioamnionitis (HCA). METHODS:
      We performed a retrospective analysis of 5849 single infants (birth weight <1500
      g) born at a gestational age between 22 + 0 and 33 + 6 weeks. Clinical data were
      obtained from the Neonatal Research Network Japan between 2003 and 2007.
      Multivariable logistic regression analyses were performed to assess the effect of
      HCA on short- and long-term outcome. RESULTS: According to logistic regression
      analysis, HCA was associated with lower incidence of respiratory distress
      syndrome (odds ratio [OR] = 0.54; p < 0.001), increased chronic lung disease (OR
      = 1.68; p < 0.001) and sepsis (OR = 1.71; p < 0.001) and as a short-term
      outcomes. There was no significant association with intraventricular hemorrhage
      (OR = 1.11; p = 0.33), periventricular leukomalacia (OR = 1.07; p = .070) and
      death before discharge (OR = 0.97; p = 0.084). HCA was associated with increased
      home oxygen therapy (OR = 3.09; p < 0.001), but not with cerebral palsy (CP; OR =
      0.91; p = 0.63), develop quotient < 70 (OR = 1.27; p = 0.17), visual impairment
      (OR = 1.08; p = 0.77), severe hearing impairment (OR = 1.28; p = 0.62) and death
      (OR = 0.98; p = 0.91) before three years of age. CONCLUSIONS: In this
      retrospective population-based study in Japan, HCA was not a risk factor for
      death, neurodevelopmental impairment and CP in VLBW three-year-old preterm
      infants.

PMID- 25567564
TI  - Effect of delivery mode on postpartum neonatal body temperatures.
AB  - OBJECTIVE: It is known that general and local anesthesia practices disrupt the
      delicate balance of thermoregulation center which is already sensitive to very
      tiny differences of temperatures in a normal subject. We aimed to evaluate and
      compare the rectal temperatures of newborns born with normal vaginal delivery and
      cesarean section. METHODS: We performed a prospective study of 106 term newborn -
      40 born with normal vaginal delivery (group 1) and 66 born with cesarean section
      [51 spinal anesthesia (group 2), 15 general anesthesia (group 3)]. Only term
      babies were included in the study. Babies of eclamptic, pre-eclamptic and
      diabetic mothers and babies with chronic systemic diseases were excluded.
      Pregnants who underwent elective cesarean section were included in the study.
      Adolescent pregnants, pregnants with increased risks and pregnants with
      complicated operations were excluded. Mothers' temperatures were measured before
      and after the interventions. Rectal temperatures of the babies were measured
      immediately after birth. RESULTS: Environmental temperature was maintained at 22
      24  degrees C. Pre-operative mother temperatures were 36.31 +/- 0.30  degrees C
      in group 1, 36.36 +/- 0.26  degrees C in group 2 and 36.39 +/- 0.19  degrees C in
      group 3 (p = 0.414). Post-operative mother temperatures were 36.39 +/- 0.27 
      degrees C in group 1, 36.29 +/- 0.31  degrees C in group 2 and 36.25 +/- 0.28 
      degrees C in group 3 (p = 0.215). Rectal temperatures of the babies born with
      normal vaginal delivery were significantly higher than the others. It was lowest
      in the general anesthesia group (37.5 +/- 0.6  degrees C, 37.2 +/- 0.2  degrees C
      and 36.8 +/- 0.4  degrees C in group 1, 2 and 3, respectively). The temperature
      differences between groups were statistically significant p < 0.001).
      CONCLUSIONS: In conclusion, it is worthy to note that temperatures of the
      newborns can differ according to the delivery mode. Physicians and health
      professionals that take care of the newborns should be aware of this difference.

PMID- 25567565
TI  - Pathologic examination of the placenta and its clinical utility: a survey of
      obstetrics and gynecology providers.
AB  - OBJECTIVE: To determine provider awareness of the College of American
      Pathologists (CAP) recommended guidelines for examination of placenta and
      evaluate the Obstetrician -Gynecologist's perception of the clinical utility of
      placenta pathology reports. STUDY DESIGN: An anonymous survey of Obstetrician
      Gynecologists who attended the national conference of The Central Association of
      Obstetricians and Gynecologists (CAOG) in 2013 assessing their knowledge of the
      CAP guidelines and utilization of information obtained from pathology reports.
      Chi-square or Fisher's exact test were used to evaluate association between
      specialists and non-specialist providers as related to survey questions and
      multivariable logistic regression used to explore factors associated with
      utilization and awareness of the guidelines. RESULTS: A total of 218 providers
      attended the conference and 111 surveys were completed. Only 36% of participants
      were aware of the CAP guidelines for pathologic examination of the placenta. The
      odds that a physician with more than 15 years of experience will send a placenta
      for examination was 0.210 times that of physicians with less than 15 years of
      experience (CI 0.084, 0.521). The odds for awareness of the CAP guideline among
      subspecialists who participated in the study were 3.630 times the odds for non
      specialist (CI 1.44, 9.147). In addition, the odds of sending a placenta for
      those physicians in a community hospital are 0.300 times that of physicians in a
      University hospital (CI 0.110, 0.820). The presence of a pathologist skilled in
      obstetrics and gynecology did not seem to affect awareness of the CAP guidelines,
      perception of the usefulness of the guidelines and likelihood of sending a
      placenta for examination. Only 21% of participants reported understanding the
      nomenclature used in pathology reports "all the time". Participants ranked the
      explanation of adverse pregnancy outcome as the most useful clinical application
      of placenta pathologic examination and most advocated for continued placental
      pathologic examination. CONCLUSION: Most of the participants in this study were
      not aware of the CAP guidelines. The study also revealed deficits in
      understanding the nomenclature on pathology reports even though providers overall
      recognized the clinical utility of pathologic examination of the placenta. This
      emphasizes the importance of actively incorporating the concept of pathologic
      changes of the placenta into the curriculum for training obstetrician
      gynecologists and pathologists and for institutions to streamline policies
      centered on pathologic examination of the placenta.

PMID- 25567566
TI  - Neurodevelopmental outcome of twins at two years of age according to the planned
      mode of delivery.
AB  - OBJECTIVES: To determine neurodevelopment at two years in twins. METHODS: At two
      years of age, all twins >=32 weeks, delivered in our center and not randomized in
      the Twin Birth Study, underwent a neurodevelopment screen using the Ages and
      Stages Questionnaire (ASQ). Children with >=1 abnormal ASQ domain score were
      evaluated by a pediatrician. Results were documented according to a planned
      cesarean section (PCS) or a planned vaginal delivery (PVD). RESULTS: An ASQ was
      obtained from 185 children (67%). No significant differences in percentages of
      abnormal scores were found between the PCS group and the PVD group or between
      twins A and B. Pediatric assessment revealed three children with a
      neurodevelopmental delay. Five other children were already under pediatric or
      general practitioner care for other reasons. One child with a congenital anomaly
      was born by a PCS, two twins A and five twins B were born in the PVD group.
      CONCLUSION: ASQ screening revealed no significant differences in abnormal
      neurodevelopment in twins at two years of age according to the mode of delivery.
      Pediatric assessment suggested an increased incidence for abnormal
      neurodevelopment in twins B born by PVD.

PMID- 25567567
TI  - Chemistry and structure in Acta Crystallographica Section C.

PMID- 25567568
TI  - Crystal structure refinement with SHELXL.
AB  - The improvements in the crystal structure refinement program SHELXL have been
      closely coupled with the development and increasing importance of the CIF
      (Crystallographic Information Framework) format for validating and archiving
      crystal structures. An important simplification is that now only one file in CIF
      format (for convenience, referred to simply as 'a CIF') containing embedded
      reflection data and SHELXL instructions is needed for a complete structure
      archive; the program SHREDCIF can be used to extract the .hkl and .ins files
      required for further refinement with SHELXL. Recent developments in SHELXL
      facilitate refinement against neutron diffraction data, the treatment of H atoms,
      the determination of absolute structure, the input of partial structure factors
      and the refinement of twinned and disordered structures. SHELXL is available free
      to academics for the Windows, Linux and Mac OS X operating systems, and is
      particularly suitable for multiple-core processors. 

PMID- 25567569
TI  - PLATON SQUEEZE: a tool for the calculation of the disordered solvent contribution
      to the calculated structure factors.
AB  - The completion of a crystal structure determination is often hampered by the
      presence of embedded solvent molecules or ions that are seriously disordered.
      Their contribution to the calculated structure factors in the least-squares
      refinement of a crystal structure has to be included in some way. Traditionally,
      an atomistic solvent disorder model is attempted. Such an approach is generally
      to be preferred, but it does not always lead to a satisfactory result and may
      even be impossible in cases where channels in the structure are filled with
      continuous electron density. This paper documents the SQUEEZE method as an
      alternative means of addressing the solvent disorder issue. It conveniently
      interfaces with the 2014 version of the least-squares refinement program SHELXL
      [Sheldrick (2015). Acta Cryst. C71. In the press] and other refinement programs
      that accept externally provided fixed contributions to the calculated structure
      factors. The PLATON SQUEEZE tool calculates the solvent contribution to the
      structure factors by back-Fourier transformation of the electron density found in
      the solvent-accessible region of a phase-optimized difference electron-density
      map. The actual least-squares structure refinement is delegated to, for example,
      SHELXL. The current versions of PLATON SQUEEZE and SHELXL now address several of
      the unnecessary complications with the earlier implementation of the SQUEEZE
      procedure that were a necessity because least-squares refinement with the now
      superseded SHELXL97 program did not allow for the input of fixed externally
      provided contributions to the structure-factor calculation. It is no longer
      necessary to subtract the solvent contribution temporarily from the observed
      intensities to be able to use SHELXL for the least-squares refinement, since that
      program now accepts the solvent contribution from an external file (.fab file) if
      the ABIN instruction is used. In addition, many twinned structures containing
      disordered solvents are now also treatable by SQUEEZE. The details of a SQUEEZE
      calculation are now automatically included in the CIF archive file, along with
      the unmerged reflection data. The current implementation of the SQUEEZE procedure
      is described, and discussed and illustrated with three examples. Two of them are
      based on the reflection data of published structures and one on synthetic
      reflection data generated for a published structure. 

PMID- 25567570
TI  - 3-Cyano-6-hydroxy-4-methyl-2-pyridone: two new pseudopolymorphs and two
      cocrystals with products of an in situ nucleophilic aromatic substitution.
AB  - Four crystal structures of 3-cyano-6-hydroxy-4-methyl-2-pyridone (CMP), viz. the
      dimethyl sulfoxide monosolvate, C7H6N2O2.C2H6OS, (1), the N,N-dimethylacetamide
      monosolvate, C7H6N2O2.C4H9NO, (2), a cocrystal with 2-amino-4-dimethylamino-6
      methylpyrimidine (as the salt 2-amino-4-dimethylamino-6-methylpyrimidin-1-ium 5
      cyano-4-methyl-6-oxo-1,6-dihydropyridin-2-olate), C7H13N4(+).C7H5N2O2(-), (3),
      and a cocrystal with N,N-dimethylacetamide and 4,6-diamino-2-dimethylamino-1,3,5
      triazine [as the solvated salt 2,6-diamino-4-dimethylamino-1,3,5-triazin-1-ium 5
      cyano-4-methyl-6-oxo-1,6-dihydropyridin-2-olate-N,N-dimethylacetamide (1/1)],
      C5H11N6(+).C7H5N2O2(-).C4H9NO, (4), are reported. Solvates (1) and (2) both
      contain the hydroxy group in a para position with respect to the cyano group of
      CMP, acting as a hydrogen-bond donor and leading to rather similar packing
      motifs. In cocrystals (3) and (4), hydrolysis of the solvent molecules occurs and
      an in situ nucleophilic aromatic substitution of a Cl atom with a dimethylamino
      group has taken place. Within all four structures, an R2(2)(8) N-H...O hydrogen
      bonding pattern is observed, connecting the CMP molecules, but the pattern
      differs depending on which O atom participates in the motif, either the ortho or
      para O atom with respect to the cyano group. Solvents and coformers are attached
      to these arrangements via single-point O-H...O interactions in (1) and (2) or by
      additional R4(4)(16) hydrogen-bonding patterns in (3) and (4). Since the in situ
      nucleophilic aromatic substitution of the coformers occurs, the possible Watson
      Crick C-G base-pair-like arrangement is inhibited, yet the cyano group of the CMP
      molecules participates in hydrogen bonds with their coformers, influencing the
      crystal packing to form chains. 

PMID- 25567571
TI  - Four (2,2'-bipyridyl)(ferrocenyl)boronium derivatives.
AB  - Crystal structures are reported for four (2,2'-bipyridyl)(ferrocenyl)boronium
      derivatives, namely (2,2'-bipyridyl)(ethenyl)(ferrocenyl)boronium
      hexafluoridophosphate, [Fe(C5H5)(C17H15BN2)]PF6, (Ib), (2,2'-bipyridyl)(tert
      butylamino)(ferrocenyl)boronium bromide, [Fe(C5H5)(C19H22BN3)]Br, (IIa), (2,2'
      bipyridyl)(ferrocenyl)(4-methoxyphenylamino)boronium hexafluoridophosphate
      acetonitrile hemisolvate, [Fe(C5H5)(C22H20BN3O)]PF6.0.5CH3CN, (IIIb), and 1,1'
      bis[(2,2'-bipyridyl)(cyanomethyl)boronium]ferrocene bis(hexafluoridophosphate),
      [Fe(C17H14BN3)2](PF6)2, (IVb). The asymmetric unit of (IIIb) contains two
      independent cations with very similar conformations. The B atom has a distorted
      tetrahedral coordination in all four structures. The cyclopentadienyl rings of
      (Ib), (IIa) and (IIIb) are approximately eclipsed, while a bisecting conformation
      is found for (IVb). The N-H groups of (IIa) and (IIIb) are shielded by the
      ferrocenyl and tert-butyl or phenyl groups and are therefore not involved in
      hydrogen bonding. The B-N(amine) bond lengths are shortened by delocalization of
      pi-electrons. In the cations with an amine substituent at boron, the B
      N(bipyridyl) bonds are 0.035 (3) A longer than in the cations with a methylene C
      atom bonded to boron. A similar lengthening of the B-N(bipyridyl) bonds is found
      in a survey of related cations with an oxy group attached to the B atom. 

PMID- 25567573
TI  - A new tetragonal structure type for Li2B2C.
AB  - The ternary dilithium diboron carbide, Li2B2C (tetragonal, space group P-4m2,
      tP10), crystallizes as a new structure type and consists of structural fragments
      which are typical for structures of elemental lithium and boron or binary
      borocarbide B13C2. The symmetries of the occupied sites are .m. and 2mm. for the
      B and C atoms, and -4m2 and 2mm. for the Li atoms. The coordination polyhedra
      around the Li atoms are cuboctahedra and 15-vertex distorted pseudo-Frank-Kasper
      polyhedra. The environment of the B atom is a ten-vertex polyhedron. The nearest
      neighbours of the C atom are two B atoms, and this group is surrounded by a
      deformed cuboctahedron with one centred lateral facet. Electronic structure
      calculations using the TB-LMTO-ASA method reveal strong B...C and B...B
      interactions. 

PMID- 25567574
TI  - Structure and magnetic properties of a mixed-ligand copper(II) complex.
AB  - The hydrothermal synthesis of the novel complex poly[[MU2-N(1),N(4)-bis(pyridin-3
      yl)naphthalene-1,4-dicarboxamide-kappa(2)N(3):N(3')](MU4-phthalato
      kappa(4)O(1):O(1):O(1'):O(2'))copper(II)], [Cu(C8H4O4)(C22H16N4O2)]n, is
      described. With the phthalate ligand connecting neighbouring Cu(II) cations, an
      infinite one-dimensional chain is formed. Adjacent one-dimensional chains are
      connected by the dicarboxamide ligand, forming an intriguing two-dimensional
      framework. The magnetic properties and thermal stability of this complex are also
      described. 

PMID- 25567572
TI  - Crystallographic investigations of select cathinones: emerging illicit street
      drugs known as 'bath salts'.
AB  - The name 'bath salts', for an emerging class of synthetic cathinones, is derived
      from an attempt to evade prosecution and law enforcement. These are truly illicit
      drugs that have psychoactive CNS (central nervous system) stimulant effects and
      they have seen a rise in abuse as recreational drugs in the last few years since
      first having been seen in Japan in 2006. The ease of synthesis and modification
      of specific functional groups of the parent cathinone make these drugs
      particularly difficult to regulate. MDPV (3,4-methylenedioxypyrovalerone) is
      commonly encountered as its hydrochloride salt (C16H21NO3.HCl), in either the
      hydrated or the anhydrous forms. This 'bath salt' has various names in the US,
      e.g. 'Super Coke', 'Cloud Nine', and 'Ivory Wave', to name just a few. We report
      here the structures of two forms of the HCl salt, one as a mixed bromide/chloride
      salt, C16H22NO3(+).0.343Br(-).0.657Cl(-) [systematic name: 1-(benzo[d][1,3]dioxol
      5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one bromide/chloride (0.343/0.657)], and
      the other with the H7O3(+) cation, as well as the HCl counter-ion [systematic
      name: hydroxonium 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1
      one dichloride, H7O3(+).C16H22NO3(+).2Cl(-)]. This is one of a very few
      structures (11 to be exact) in which we have a new example of a precisely
      determined hydroxonium cation. During the course of researching the clandestine
      manufacture of MDPV, we were surprised by the fact that a common precursor of
      this illicit stimulant is known to be the fragrant species piperonal, which is
      present in the fragrances of orchids, most particularly in the case of the
      vanilla orchid. We found that MDPV can be made by a Grignard reaction of this
      heliotropin. This may also explain the unexpected appearance of the bromide
      counter-ion in some of the salts we encountered (C16H21NO3.HBr), one of which is
      presented here [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium
      1-yl)pentan-1-one bromide, C16H22NO3(+).Br(-)]. Complexation of MDPV with a
      forensic crystallizing reagent, HAuCl4, yields the tetrachloridoaurate salt of
      this drug, (C16H22NO3)[AuCl4]. The heavy-metal complexing agent HAuCl4 has been
      used for over a century to identify common quarternary nitrogen-containing drugs
      via microscopic identification. Another street drug, called ethylone (3,4
      methylenedioxyethylcathinone), is regularly sold and abused as its hydrochloride
      salt (C12H15NO3.HCl), and its structure is herein described (systematic name: N
      {1-[(benzo[d][1,3]dioxol-5-yl)carbonyl]ethyl}ethanaminium chloride,
      C12H16NO3(+).Cl(-)). Marketed and sold as a 'bath salt', 'plant feeder', or
      'cleaning product', this drug is nothing more than a slight chemical modification
      of the banned drug methylone (3,4-methylenedioxymethcathinone). As with
      previously popular synthetic cathinones, the abuse of ethylone has seen a recent
      increase due to regulatory efforts on previous generations of cathinones that are
      now banned. 

PMID- 25567575
TI  - Two novel organic-inorganic hybrid materials from tetrachloridometallate(II)
      salts and 4-[(E)-2-(pyridin-1-ium-2-yl)ethenyl]pyridinium.
AB  - Two organic-inorganic hybrid compounds have been prepared by the combination of
      the 4-[(E)-2-(pyridin-1-ium-2-yl)ethenyl]pyridinium cation with perhalometallate
      anions to give 4-[(E)-2-(pyridin-1-ium-2-yl)ethenyl]pyridinium
      tetrachloridocobaltate(II), (C12H12N2)[CoCl4], (I), and 4-[(E)-2-(pyridin-1-ium-2
      yl)ethenyl]pyridinium tetrachloridozincate(II), (C12H12N2)[ZnCl4], (II). The
      compounds have been structurally characterized by single-crystal X-ray
      diffraction analysis, showing the formation of a three-dimensional network
      through X-H...ClnM(-) (X = C, N(+); n = 1, 2; M = Co(II), Zn(II)) hydrogen
      bonding interactions and pi-pi stacking interactions. The title compounds were
      also characterized by FT-IR spectroscopy and thermogravimetric analysis (TGA). 

PMID- 25567576
TI  - On substituted pyrazole derivatives. II. (E)-1-(4-{[1-(4-Fluorophenyl)-3,5
      dimethyl-1H-pyrazol-4-yl]diazenyl}phenyl)ethanone and (E)-1-(4-chlorophenyl)-3,5
      dimethyl-4-[2-(2-nitrophenyl)diazenyl]-1H-pyrazole.
AB  - The molecular structures of (E)-1-(4-{[1-(4-fluorophenyl)-3,5-dimethyl-1H-pyrazol
      4-yl]diazenyl}phenyl)ethanone, C19H17FN4O, (III), and (E)-1-(4-chlorophenyl)-3,5
      dimethyl-4-[2-(2-nitrophenyl)diazenyl]-1H-pyrazole, C17H14ClN5O2, (IV), prepared
      by reaction of the corresponding beta-diketohydrazones with substituted
      arylhydrazines in acid media, are nonplanar, with the planes of the lateral
      phenyl rings forming dihedral angles with that of the central pyrazole ring
      varying from 2.71 (7) to 45.22 (7) degrees . The crystal structures are supported
      by C-H...O, C-H...pi and pi-pi weak intermolecular interactions together with
      some unusual trifurcated C-Cl...Cl-C contacts, which are discussed in detail. 

PMID- 25567577
TI  - Ethyl (4-benzyloxyphenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5
      carboxylate and a redetermination of ethyl (4RS)-4-(4-methoxyphenyl)-6-methyl-2
      sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate, as its 0.105-hydrate,
      both at 200 K: subtly different hydrogen-bonded ribbons.
AB  - Two sulfanylidene-1,2,3,4-tetrahydropyrimidine derivatives have been synthesized
      using acid-catalysed cyclocondensation reactions between thiourea, ethyl 3
      oxobutanoate and substituted benzaldehydes. In each of ethyl (4RS)-4-(4
      benzyloxyphenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5
      carboxylate, C21H22N2O3S, (I), where Z' = 2, and ethyl (4RS)-4-(4-methoxyphenyl)
      6-methyl-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carboxylate 0.105
      hydrate, C15H18N2O3S.0.105H2O, (II), the reduced pyrimidine ring adopts a
      conformation intermediate between the boat, screw-boat and twist-boat forms. In
      (I) and (II), a combination of N-H...O and N-H...S hydrogen bonds links the
      organic molecules into ribbons containing alternating R2(2)(8) and R4(4)(20)
      rings. In (I), the ribbon contains three types of ring, viz. two different
      R2(2)(8) rings which are both centrosymmetric and R4(4)(20) rings which are not
      centrosymmetric. In (II), the ribbon contains two types of ring, both of which
      are centrosymmetric. In compound (II), the ribbons enclose continuous channels
      which run along the twofold rotation axes in the space group C2/c, and the
      partial-occupancy water molecules lie within these channels. Structural
      comparisons are made with a number of related compounds. 

PMID- 25567578
TI  - A three-dimensional anionic metal-dicyanamide network in
      poly[ethyltriphenylphosphonium [tri-MU2-dicyanamidato-cadmium(II)]].
AB  - The title compound, (C20H20P)[Cd(C2N3)3], consists of ethyltriphenylphosphonium
      (EtPh3P(+)) cations filling voids in a three-dimensional anionic cadmium
      dicyanamide network. In the structure, each Cd(II) atom is connected to six
      neighbouring Cd(II) atoms through six separate dicyanamide ligands, forming cube
      shaped cages. The three-dimensional anionic network encloses a solvent-accessible
      void space of 1851 A(3), amounting to 69.3% of the unit-cell volume. Each cage
      accommodates only one EtPh3P(+) cation. 

PMID- 25567579
TI  - Three 1-phenylindolin-2-one derivatives displaying different molecular dipole
      moments and different crystallographic symmetries.
AB  - Three 1-phenylindolin-2-one derivatives, namely 1-phenylindolin-2-one, C14H11NO,
      (I), 5-bromo-1-phenylindolin-2-one, C14H10BrNO, (II), and 5-iodo-1-phenylindolin
      2-one, C14H10INO, (III), have been synthesized and their structures determined.
      Compounds (I) and (II) crystallized in the centrosymmetric space groups Pbca and
      P21/c, respectively, while compound (III) crystallized in the polar space group
      Aea2. Density functional theory (DFT) calculations show that the molecular dipole
      moment gradually decreases in the order (I) > (II) > (III). The relatively
      smaller dipole moment of (III) and the larger non-electrostatic intermolecular
      interactions may be the main reasons for the noncentrosymmetric and polar
      structure of (III). 

PMID- 25567580
TI  - Cocrystals of the antibiotic trimethoprim with glutarimide and 3,3
      dimethylglutarimide held together by three hydrogen bonds.
AB  - The antibiotic trimethoprim [5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine]
      was cocrystallized with glutarimide (piperidine-2,6-dione) and its 3,3-dimethyl
      derivative (4,4-dimethylpiperidine-2,6-dione). The cocrystals, viz. trimethoprim
      glutarimide (1/1), C14H18N4O3.C5H7NO2, (I), and trimethoprim-3,3
      dimethylglutarimide (1/1), C14H18N4O3.C7H11NO2, (II), are held together by three
      neighbouring hydrogen bonds (one central N-H...N and two N-H...O) between the
      pyrimidine ring of trimethoprim and the imide group of glutarimide, with an
      ADA/DAD pattern (A = acceptor and D = donor). These heterodimers resemble two
      known cocrystals of trimethoprim with barbituric acid and its 5,5-diethyl
      derivative. Trimethoprim shows a conformation in which the planes of the
      pyrimidine and benzene rings are approximately perpendicular to one another. In
      its glutarimide coformer, five of the six ring atoms lie in a common plane; the C
      atom opposite the N atom deviates by about 0.6 A. The crystal packing of each of
      the two cocrystals is characterized by an extended network of hydrogen bonds and
      contains centrosymmetrically related trimethoprim homodimers formed by a pair of
      N-H...N hydrogen bonds. This structural motif occurs in five of the nine
      published crystal structures in which neutral trimethoprim is present. 

PMID- 25567581
TI  - Ca3ZnGeO2[Ge4O12]: a Ca-Zn germanate related to the mineral taikanite.
AB  - The title compound, Ca3ZnGeO2[Ge4O12] (tricalcium zinc germanium dioxide
      dodecaoxidotetragermanate), adopts a taikanite-type structure. The tetrahedral
      [Ge4O12] chain geometry is very similar to that of the silicate chain of
      taikanite, i.e. BaSr2Mn(3+)2O2[Si4O12], while the major difference is found
      parallel to the c axis. In taikanite, Mn(3+) octahedra form an infinite zigzag
      chain, whereas the title compound has a chain of distorted ZnO6 octahedra, which
      alternates with distorted GeO4 tetrahedra connected to each other via two common
      edges. Eightfold-coordinated Ca(2+) polyhedra and ZnO6 octahedra form a slab
      parallel to (001) which alternates with another slab containing the tetrahedrally
      coordinated Ge sites along the c axis. 

PMID- 25567582
TI  - Leukaemia: exploring origins and evolution.

PMID- 25567583
TI  - A meta-analysis of ventriculostomy-associated cerebrospinal fluid infections.
AB  - BACKGROUND: Ventriculostomy insertion is a common neurosurgical intervention and
      can be complicated by ventriculostomy-associated cerebrospinal fluid infection
      (VAI) which is associated with increased morbidity and mortality. This meta
      analysis was aimed at determining the pooled incidence rate (number per 1000
      catheter-days) of VAI. METHODS: Relevant studies were identified from MEDLINE and
      EMBASE and from reference searching of included studies and recent review
      articles on relevant topics. The Newcastle-Ottawa Scale was used to assess
      quality and risk of bias. A random effects model was used to pool individual
      study estimates and 95% confidence intervals (CI) were calculated using the exact
      Poisson method. Heterogeneity was assessed using the heterogeneity chi2 and I
      squared tests. Subgroup analyses were performed and a funnel plot constructed to
      assess publication bias. RESULTS: There were a total of 35 studies which yielded
      752 infections from 66,706 catheter-days of observation. The overall pooled
      incidence rate of VAI was 11.4 per 1000 catheter days (95% CI 9.3 to 13.5), for
      high quality studies the rate was 10.6 (95% CI 8.3 to 13) and 13.5 (95% CI 8.9 to
      18.1) for low quality studies. Studies which had mean duration of EVD treatment
      of less than 7 days had a pooled VAI rate of 19.6 per 1000 catheter-days, those
      with mean duration of 7-10 days had VAI rate of 12.8 per 1000 catheter-days and
      those with mean duration greater than 10 days had VAI rate of 8 per 1000 catheter
      days. There was significant heterogeneity for the primary outcome (p = 0.004, I
      squared = 44%) and most subgroups. The funnel plot did not show evidence for
      publication bias. CONCLUSIONS: The incidence rate of VAI is 11.4 per 1000
      catheter-days. Further research should focus on analysis of risk factors for VAI
      and techniques for reducing the rate of VAI.

PMID- 25567585
TI  - Universal order parameters and quantum phase transitions: a finite-size approach.
AB  - We propose a method to construct universal order parameters for quantum phase
      transitions in many-body lattice systems. The method exploits the H-orthogonality
      of a few near-degenerate lowest states of the Hamiltonian describing a given
      finite-size system, which makes it possible to perform finite-size scaling and
      take full advantage of currently available numerical algorithms. An explicit
      connection is established between the fidelity per site between two H-orthogonal
      states and the energy gap between the ground state and low-lying excited states
      in the finite-size system. The physical information encoded in this gap arising
      from finite-size fluctuations clarifies the origin of the universal order
      parameter. We demonstrate the procedure for the one-dimensional quantum
      formulation of the q-state Potts model, for q = 2, 3, 4 and 5, as prototypical
      examples, using finite-size data obtained from the density matrix renormalization
      group algorithm. 

PMID- 25567584
TI  - Improving the implementation of perioperative safety guidelines using a
      multifaceted intervention approach: protocol of the IMPROVE study, a stepped
      wedge cluster randomized trial.
AB  - BACKGROUND: This study is initiated to evaluate the effects, costs, and
      feasibility at the hospital and patient level of an evidence-based strategy to
      improve the use of Dutch perioperative safety guidelines. Based on current
      knowledge, expert opinions and expertise of the project team, a multifaceted
      implementation strategy has been developed. METHODS/DESIGN: This is a stepped
      wedge cluster randomized trial including nine representative hospitals across The
      Netherlands. Hospitals are stratified into three groups according to hospital
      type and geographical location and randomized in terms of the period for receipt
      of the intervention. All adult surgical patients meeting the inclusion criteria
      are assessed for patient outcomes. The implementation strategy includes
      education, audit and feedback, organizational interventions (e.g., local
      embedding of the guidelines), team-directed interventions (e.g., multi
      professional team training), reminders, as well as patient-mediated interventions
      (e.g., patient safety cards). To tailor the implementation activities, we
      developed a questionnaire to identify barriers for effective guideline adherence,
      based on (a) a theoretical framework for classifying barriers and facilitators,
      (b) an instrument for measuring determinants of innovations, and (c) 19 semi
      structured interviews with perioperative key professionals. Primary outcome is
      guideline adherence measured at the hospital (i.e., cluster) and patient levels
      by a set of perioperative Patient Safety Indicators (PSIs), which was developed
      parallel to the perioperative guidelines. Secondary outcomes at the patient level
      are in-hospital complications, postoperative wound infections and mortality,
      length of hospital stay, and unscheduled transfer to the intensive care unit, non
      elective readmission to the hospital and unplanned reoperation, all within 30
      days after the initial surgery. Also, patient safety culture and team climate
      will be studied as potential determinants. Finally, a process evaluation is
      conducted to identify the compliance with the implementation strategy, as well as
      an economic evaluation to assess the costs. Data sources are registered clinical
      data and surveys. There is no form of blinding. DISCUSSION: The perioperative
      setting is an unexplored area with respect to implementation issues. This study
      is expected to yield important new evidence about the effects of a multifaceted
      approach on guideline adherence in the perioperative care setting. TRIAL
      REGISTRATION: Dutch trial registry: NTR3568.

PMID- 25567586
TI  - Decontamination of nanoparticles from aqueous samples using supramolecular gels.
AB  - The growing use of nanomaterials and their associated risks necessitate the
      emergence of efficient decontamination systems. The main objective of this study
      is to develop a new prototype based on artificial supramolecular hydrogel capable
      of removing nanoparticle (NP) waste and nanomaterial by-products from aqueous
      suspensions. We demonstrate the high trapping efficacy of the low-molecular
      weight gelators (LMWG) for very small particles (quantum dots (QDs), gold
      nanoparticles (AuNPs), TiO2 nanoparticles (TiO2-NPs), below 50 nm in diameter)
      from aqueous suspensions. The performance levels of removing nanoparticles from
      contaminated effluents could lead to a competitive alternative to filtration and
      dialysis devices. 

PMID- 25567588
TI  - [Introduction of WHO classification of tumours of female reproductive organs,
      fourth edition].

PMID- 25567589
TI  - [Expression of proteins related neurodegeneration in autopsy brains of the aged].
AB  - OBJECTIVE: To recognize relationship of protein related neurodegeneration
      abnormal aggregation in the aged brains with their cognitive and motor functions.
      METHODS: Brain tissues from the consecutive autopsy cases of the aged from
      January 2005 to December 2006 in PLA General Hospital were carried out for
      immunohistochemical staining with beta amyloid, tau, alpha-synuclein and
      ubiquitin antibodies. The consortium to establish a registry for Alzheimer's
      disease (CERAD) was used to semi-quantitatively analyze Abeta positive core
      plaques density and Braak staging for tau positive neurofibrillary tangles (NFTs)
      and alpha-synuclein positive Lewy bodies. In addition, Abeta positive cerebral
      amyloid angiopathy (CAA), neuritic plaques and various ubiquitin positive
      structures were also observed. The relationship of these protein abnormal
      depositions in the aged brains with cognitive and motor functions were analyzed.
      RESULTS: In brain tissues of 16 consecutive autopsy cases of the aged from 78 to
      95 years, there were 13 cases with Abeta positive core plaques, their density was
      2 cases with sparse, 2 cases with moderate and 9 cases with frequent,
      respectively, according to CREAD.Eight cases with Abeta positive CAA were found,
      including 6 cases of mild CAA and 2 cases of severe CAA. There were 12 cases with
      tau positive NFTs, including 6 cases with Braak stageI-II, 4 cases with stage III
      IV and 2 cases with stage V-VI. There were 5 cases with frequent Abeta core
      plaques, meanwhile existing numerous tau/ubiquitin positive neuritic plaques and
      Braak stage IV-VI of tau positive NFTs, all of them presented cognitive
      dysfunction. Among 4 other cases with frequent Abeta core plaques, only one case
      coexisted alpha-synuclein positive Lewy bodies showed moderate cognitive
      impairment, remaining 3 cases did not present cognitive dysfunction. There were 4
      cases with alpha-synuclein positive Lewy bodies in the brainstem, and all of
      these cases presented parkinsonian motor dysfunction. 13 cases with ubiquitin
      positive structures were found. CONCLUSIONS: Beta amyloid protein positive
      deposit in the aged brain is an important marker of normal brain aging and
      cognitive impairment; frequent Abeta core plaques in the neocortex plus Braak IV
      and above tau positive NFTs are closely related to cognitive dysfunction of
      Alzheimer's disease; alpha-synuclein positive Lewy bodies in the brainstem is one
      of the important pathological markers of parkinsonian motor disorders; ubiquitin
      deposition involves the development of some characteristic structures of several
      neurodegenerative diseases.

PMID- 25567587
TI  - Rapid, sensitive and real-time multiplexing platform for the analysis of protein
      and nucleic-acid biomarkers.
AB  - We describe a multiplexing technology, named Evalution, based on novel digitally
      encoded microparticles in microfluidic channels. Quantitative multiplexing is
      becoming increasingly important for research and routine clinical diagnostics,
      but fast, easy-to-use, flexible and highly reproducible technologies are needed
      to leverage the advantages of multiplexing. The presented technology has been
      tailored to ensure (i) short assay times and high reproducibility thanks to
      reaction-limited binding regime, (ii) dynamic control of assay conditions and
      real-time binding monitoring allowing optimization of multiple parameters within
      a single assay run, (iii) compatibility with various immunoassay formats such as
      coflowing the samples and detection antibodies simultaneously and hence
      simplifying workflows, (iv) analyte quantification based on initial binding rates
      leading to increased system dynamic range and (v) high sensitivity via enhanced
      fluorescence collection. These key features are demonstrated with assays for
      proteins and nucleic acids showing the versatility of this technology. 

PMID- 25567590
TI  - [Gliosarcoma of cerebral hemispheres: a clinicopathologic study of 10 cases].
AB  - OBJECTIVE: To study the clinical and pathologic features of gliosarcoma of
      cerebral hemispheres. METHODS: The clinicopathologic features of 10 cases of
      gliosarcoma involving cerebral hemispheres were reviewed. Immunohistochemical
      study was carried out using EnVision method. RESULTS: The mean age of the
      patients was 54 years and the male-to-female ratio was 6 to 4. Clinical symptoms
      included headache (6/10), nausea/vomiting (5/10), and sensory or motor impairment
      (4/10). Nine of the cases were primary gliosarcoma, with maximum diameter ranging
      from 2.4 to 5.5 cm (mean = 4.2 cm). The remaining case represented secondary
      gliosarcoma involving skull base and extracranial tissues. Histologic examination
      showed a biphasic pattern in all cases. Regarding the glial component, there were
      9 cases of pleomorphic glioblastoma and 1 case of giant cell glioblastoma.
      Reticulin stain was positive in all cases. Immunohistochemical study showed that
      the tumor cells variably expressed GFAP (10/10), p16 (4/10), EGFR (1/10), CD68
      (1/10) and p53 (6/10). The Ki-67 index ranged from 15% to 70% (mean = 34%). Six
      patients had follow-up data available. One patient was disease-free for 45 months
      and 5 patients died of the disease at 3 to 17 months after the operation (mean
      duration of survival = 9 months). CONCLUSIONS: Gliosarcoma is a highly aggressive
      tumor, often locates in the deeper part cerebral hemispheres and has a relatively
      short duration of symptoms. It carries a poor prognosis. GFAP immunostain and
      reticulin stain are helpful in confirming the diagnosis. p53 and p16 are also
      expressed in some cases.

PMID- 25567591
TI  - [Correlation of chromosome 1p and 19q status and expression of R132H mutant IDH1
      protein in oligodendroglial tumors].
AB  - OBJECTIVE: To correlate the presence of chromosome 1p/19q deletion with the
      expression of R132H mutant IDH1 status in oligodendroglial tumors, and to explore
      molecular markers for predicting chemosensitivity of oligodendroglial tumors.
      METHODS: The study included 75 oligodendroglial tumors (38 oligodendrogliomas and
      37 oligoastrocytomas). Immunohistochemistry was used to detect the expression of
      R132H mutant IDH1 protein, and fluorescence in situ hybridization (FISH) was
      employed to detect 1p/19q deletion. RESULTS: Deletion of chromosome 1p and/or 19q
      was detected in 37 cases (37/75, 49.3%), among which co-deletion of 1p and 19q
      was seen in 34 cases (closely correlated, P < 0.01). Oligodendrogliomas WHOIIhad
      a slightly higher deletion rate than oligodendrogliomas WHO III, although without
      statistical significance. Oligodendrogliomas WHO IIand WHO III had a
      significantly higher deletion rate of chromosome 1p/19q than oligoastrocytomas
      WHO II and WHO III (P < 0.05). While combined loss of 1p/19q was always detected
      in oligodendrogliomas when FISH was positive, isolated 1p or 19q deletion was
      only found in oligoastrocytomas. The expression of R132H mutant IDH1 was detected
      in 51 of 75 cases (68.0%), in which oligodendrogliomas had a higher positive rate
      than oligoastrocytomas. Statistical analysis demonstrated a significant
      correlation between the expression of R132H mutant IDH1 protein and the presence
      of combined 1p/19q deletion in oligodendrogliomas (P < 0.05). CONCLUSIONS: A
      significant correlation was observed between the expression of R132H mutant
      protein and 1p/19q LOH.Expression of 132H mutant IDH1 protein is the potential
      biomarker for predicating the presence of 1p/19q deletion in oligodendrogliomas.

PMID- 25567592
TI  - [IDH1 mutation and MGMT expression in astrocytoma and the relationship with
      prognosis after radiotherapy].
AB  - OBJECTIVE: To study the correlation between IDH1 mutation, MGMT expression,
      clinicopathologic features and post-radiotherapy prognosis in patients with
      astrocytoma. METHODS: Detection of IDH1 mutation and MGMT expression was carried
      out in 48 cases of astrocytoma (WHO grade II to III) by EnVision method with
      immunohistochemical staining. Follow-up data, including treatment response and
      overall survival time, were analyzed. RESULTS: The rates of IDH1 mutation and
      MGMT expression in astrocytomas were 62.7% (30/48) and 47.9% (23/48),
      respectively. There was a negative correlation between IDH1 mutation and MGMT
      expression (r = -0.641, P < 0.01). The age of patients with IDH1 mutation was
      younger at disease onset. The IDH1 mutation rate in patients with WHO grade II
      astrocytoma was higher than that in patients with WHO grade III tumor (P < 0.05).
      The age at onset was an independent factor affecting the expression of mutant
      IDH1. After radiotherapy, patients with IDH1 mutation+/MGMT- tumor carried a
      longer overall survival time than patients with IDH1 mutation-/MGMT+ tumor (P <
      0.05). CONCLUSIONS: There is a correlation between IDH1 mutation and MGMT
      expression in WHO grade II to III astrocytoma. Age at onset is an independent
      factor affecting the expression of mutant IDH1. Tumors with IDH1+/MGMT- pattern
      show better response to radiotherapy than tumors with IDH1-/MGMT+ pattern.
      Detection of IDH1 mutation and MGMT protein expression can provide some guidance
      in choice of treatment modalities in patients with astrocytoma.

PMID- 25567594
TI  - [Impact of International Association of Urological Pathology Gleason scoring
      system on prostatic carcinoma grading: a preliminary analysis of 185 cases].
AB  - OBJECTIVE: To explore the impact of the 2005 International Association of
      Urological Pathology (ISUP) Gleason score (GS) system on prostatic carcinoma
      grading. METHODS: Using the 1977 revision and ISUP version of GS system, 112
      needle biopsies, 18 transurethral resections of the prostate and 55 radical
      prostatectomies were scored. The proportion of grading discrepancy was observed
      and compared between the two versions of GS. RESULTS: Gleason scores of 3+3, 3+4
      and 4+3 accounted for 47.0% (87/185), 11.4% (21/185) and 17.3% (32/185) in the
      modified system, and accounted for 25.9% (48/185), 21.6% (40/185) and 27.6 %
      (51/185) in ISUP system, respectively. The percentages of primary grade by
      modified vs. ISUP system were 62.7% (116/185) vs.50.8% (94/185) for grade 3, and
      31.4% (58/185) vs. 41.6% (77/185) for grade 4. The percentages of secondary grade
      by modified vs. ISUP system were 65.9% (122/185) vs. 54.6% (101/185) for grade 3,
      and 21.1% (39/185) vs. 31.4% (58/185) for grade 4. CONCLUSIONS: ISUP system is
      different from the modified system. Compared with the modified system, the
      proportion scored by ISUP system tends to decline for GS 3+3 but increase for GS
      3+4 and 4+3.

PMID- 25567593
TI  - [Pathologic analysis of primary cardiac inflammatory myofibroblastic tumor].
AB  - OBJECTIVE: To study the clinical and pathologic features of primary cardiac
      inflammatory myofibroblastic tumor. METHODS: A total of 4 patients with primary
      cardiac inflammatory myofibroblastic tumor were encountered during the period
      from 1993 to 2013 in National Center for Cardiovascular Disease. The clinical
      features, imaging findings and outcomes of the 4 patients were evaluated. ALK
      protein expression and ALK gene status were studied using the archival tumor
      tissues. RESULTS: There were 1 female and 3 male patients. The age of patients
      ranged from 5 months to 30 years (mean = 16 years). The tumor was located in
      right ventricle (n = 2), right atrium (n = 1) or pericardium (n = 1). Histologic
      patterns included 2 cases of fibrous histiocytoma type, 1 case of granulomatous
      type and 1 case of sclerosing type. Immunohistochemical study showed that 2 cases
      expressed ALK protein. Fluorescence in-situ hybridization however did not reveal
      any ALK gene rearrangement. CONCLUSIONS: Inflammatory myofibroblastic tumor of
      the heart is rarely encountered and easily misdiagnosed. It carries distinctive
      clinical and pathologic features. ALK protein expression is helpful in arriving
      at the correct diagnosis.

PMID- 25567595
TI  - [Significance of CD123 in histiocytic necrotizing lymphadenitis].
AB  - OBJECTIVE: To investigate the mode of presentation, cytologic features of the
      plasmacytoid dendritic cells (pDC), and the expression of CD123 and its
      significance in Kikuchi's disease. METHODS: CD123 expression was evaluated by
      EliVision immunohistochemical staining in formalin-fixed and paraffin-embedded
      tissues from 30 cases of Kikuchi's disease, 5 cases of T cell lymphoma, 10 cases
      of reactive lymphoid hyperplasia and 10 cases of chronic tonsillitis. RESULTS:
      Clusters of CD123 positive PDC were observed in Kikuchi's disease (28 of 30
      cases, 93.3%) and the staining intensity was more prominent in the PDC at the
      periphery of the lesion and around the high endothelial venule-like vessels.
      CD123 showed three staining patterns: membranous (10 cases, 33.3%), cytoplasmic
      (10 cases, 33.3%), and membranous and cytoplasmic (8 cases, 26.7%). In the
      control group, CD123 showed cytoplasmic staining in reactive hyperplasia and
      chronic tonsillitis. Regarding the staining intensity, 12 of 28 cases (42.9%)
      were 3+ for CD123, 8 of 28 cases (28.6%) were 2+, and 8 of 28 cases (28.6%) were
      1+. In contrast, PDC clusters with 1+ staining intensity were observed in 1 of 10
      cases of reactive lymphoid hyperplasia; 2 of 10 chronic tonsillitis diseases; and
      much less in T cell lymphoma. CONCLUSIONS: Large cluster of PDC is detected in
      both proliferative and necrotizing types of Kikuchi's disease, making this a
      useful adjunctive diagnostic marker.

PMID- 25567596
TI  - [Hepatic epithelioid angiomyolipoma: a clinicopathologic analysis of 25 cases].
AB  - OBJECTIVE: To study the clinicopathologic features, immunophenotype, histological
      diagnosis and prognosis of hepatic epithelioid angiomyolipoma. METHODS: Clinical
      data of 25 cases of hepatic epithelioid angiomyolipoma were collected along with
      follow-up study of the patients. The pathological features were documented and
      immunohistochemical study of various markers was performed with an emphasis on
      diagnosis and differential diagnosis. RESULTS: Hepatic epithelioid angiomyolipoma
      was more commonly found in young women without characteristic clinical symptoms.
      Its morphological features were characterized by marked cytological atypia,
      relatively rare mitotic figures; radial distribution of tumor cells around the
      thin-walled blood vessels or muscular vessels; and the presence of common
      multinucleated giant cells and large ganglion-like tumor cells. The tumor cells
      expressed both melanoma cell markers (HMB45, MART-1) and smooth muscle cell
      markers (SMA). Tumor cells expressed various other markers including ER 16%
      (4/25), PR 32% (8/25), TFE3 24% (6/25) and p53 60% (15/25). CONCLUSIONS: Hepatic
      epithelioid angiomyolipoma has variable morphological features and characteristic
      immunohistochemical phenotype. The differential diagnoses include a variety of
      tumors. The biological behavior of the tumor tends to be benign.

PMID- 25567597
TI  - [Multiple Rosai-Dorfman disease: a clinicopathologic analysis of 7 cases].
AB  - OBJECTIVE: To investigate the clinicopathologic features, diagnosis, differential
      diagnosis of multiple Rosai-Dorfman disease (RDD). METHODS: Seven cases of
      multiple RDD were treated in Fujian Provincal Hospital and Fuzhou General
      Hospital of Nanjing Military Command of Chinese PLA. The disease was analyzed,
      focusing on the process of diagnosis, the treatment and follow-up.
      Histopathology, immunohistochemical profiles and relative literature were
      reviewed to reveal the characteristics of this disease. RESULTS: The seven cases,
      occurred in 3 women and 4 men from 18 to 60 years of age (median 45.71 years),
      with masses measured of 0.8-6.0 cm (average size of 3.0 cm). Masses located in,
      left subcutaneous arm, thyroid, paratrachea, left maxilla, right subcutaneous
      cheek, left subcutaneous chest wall, right subcutaneous inguina, bilateral
      subcutaneous neck, right tibia, right thigh skin, right frontal lobe of brain,
      cerebral parafalx and bilateral lymph nodes of the neck, respectively. Among the
      cases, from the first case to the sixth case were extranodal tissue, and the
      seventh case was located in lymph nodes. Cases showed progressive increase of the
      mass. Histologically, all lesions of seven cases were similar with nodular
      structures presenting with alternating hyper- and hypo-cellular areas. The hypo
      cellular areas revealed lymph-sinustoid structure characterized by variable
      numbers of large histiocytes, which had an abundant cytoplasm, pale to
      eosinophilic in appearance, phagocytozed intact lymphocytes or emperipolesis.
      While hyper-cellular areas revealed the infiltration of lymphocytes, plasma
      cells, neutrophils and numerous collagen fiber. Two cases also revealed the
      infiltration of lymphoid follicles. Immunohistochemically, the large histiocytes
      were strongly positive for S-100, CD163 and CD68 protein. CONCLUSIONS: Multiple
      RDD is rare. In clinic and pathology, it needs to be differentiated from
      granulomatous diseases, IgG4-related sclerotic diseases, inflammatory
      myofibroblastic tumor, fibrohistiocytoma, Langerhans cell histiocytosis, and so
      on. The primary approach of treatment for multiple RDD is complete surgical
      excision and its prognosis is good.

PMID- 25567599
TI  - [Multifocal meningeal melanocytoma with repeated recurrence: report of a case].

PMID- 25567598
TI  - [Impact of PTTG1 downregulation on cell proliferation, cell cycle and cell
      invasion of osteosarcoma and related molecular mechanisms].
AB  - OBJECTIVE: To downregulate the expression of pituitary tumor transforming gene 1
      (PTTG1) in osteosarcoma (OS) cells by siRNA technology and to investigate related
      biological impact on cell proliferation, cell cycle and cell invasion of OS.
      METHODS: Three OS cell lines and osteoblast hFOB1.19 cell line were used in this
      study. Control siRNA and PTTG1 siRNA were employed to transfect OS U2OS cells,
      and PTTG1 protein level was detected by Western blot after the transfection.
      Effects of PTTG1 siRNA on cell proliferation, cell cycle and cell invasion were
      investigated by CCK-8, flow cytometry and Boyden chamber, respectively. Finally,
      activity of Akt and its downstream target gene expression were analyzed by
      Western blot in U2OS cells upon various treatments. RESULTS: Expression of PTTG1
      protein in 3 OS cells (MG-63, SaOS-2 and U2OS) was significantly higher than that
      in osteoblast hFOB1.19, among which U2OS cells displayed the highest level. PTTG1
      siRNA markedly downregulated the expression of PTTG1 protein in U2OS cells,
      leading to obvious inhibition of cell proliferation, altered cell cycle
      distribution and reduced ability of invasion of U2OS cells. Moreover,
      downregulation of PTTG1 reduced the expression of p-Akt (S473 and T308), MMP-2
      and MMP-9 proteins, along with enhanced expression of p21 and E-cadherin
      proteins. CONCLUSIONS: PTTG1 may be tightly linked to the development of OS and
      therefore may serve as a novel target for precision therapy of OS.

PMID- 25567600
TI  - [Warty dyskeratoma: report of a case].

PMID- 25567601
TI  - [Cryptococcal lymphadenitis in groin lymph node: report of a case].

PMID- 25567602
TI  - [Primary cutaneous gamma/delta T-cell lymphoma: report of 2 cases].

PMID- 25567603
TI  - [Sclerosing rhabdmyosarcoma of the retroperitoneum: report of a case].

PMID- 25567604
TI  - [Pathologic diagnosis of epithelioid soft tissue tumors].

PMID- 25567605
TI  - [gammaH2AX and its application in clinical tumor research].

PMID- 25567606
TI  - [Origin and pathogenesis of benign metastasizing leiomyoma].

PMID- 25567609
TI  - Editorial for January 2015 for JPC A/B/C.

PMID- 25567608
TI  - Embryonic expression of shuttle craft, a Drosophila gene involved in neuron
      development, is associated with adult lifespan.
AB  - Despite the progress in aging research that highlights the role of the nervous
      system in longevity, whether genes that control development and consequently
      structure of the nervous system affect lifespan is unclear. We demonstrated that
      a mutation inshuttle craft, a gene involved in the nervous system development,
      increased the lifespan of unmated females and decreased the lifespan of mated
      females, without affecting males. Precise reversions of the mutation lead to the
      restoration of the lifespan specific to control females. In mutant unmated
      females, increased lifespan was associated with elevated locomotion at older
      ages, indicating slowed aging. In mutant mated females, reproduction was
      decreased compared to controls, indicating a lack of tradeoff between this trait
      and lifespan. No differences in shuttle craft transcription were observed between
      whole bodies, ovaries, and brains of mutant and control females of different
      ages, either unmated or mated. The amount of shuttle craft transcript appeared to
      be substantially decreased in mutant embryos. Our results demonstrated that a
      gene that regulates development of the nervous system might also influence
      longevity, and thus expanded the spectrum of genes involved in lifespan control.
      We hypothesize that this "carry-over" effect might be the result of transcription
      regulation in embryos.

PMID- 25567610
TI  - The simulation method in learning interpersonal communication competence-
      experiences of masters' degree students of health sciences.
AB  - BACKGROUND: This article describes the experiences of master students of nursing
      science in learning interpersonal communication competence through the simulation
      method. The exercises reflected challenging interactive situations in the field
      of health care. Few studies have been published on using the simulation method in
      the communication education of teachers, managers, and experts in this field.
      OBJECTIVES: The aim of this study is to produce information which can be utilised
      in developing the simulation method to promote the interpersonal communication
      competence of master-level students of health sciences. DESIGN: This study used
      the qualitative, descriptive research method. SETTINGS: At the Department of
      Nursing Science, the University of Eastern Finland, students major in nursing
      science specialise in nursing leadership and management, preventive nursing
      science, or nurse teacher education. PARTICIPANTS: Students from all three
      specialties taking the Challenging Situations in Speech Communication course
      participated (n=47). METHODS: Essays on meaningful learning experiences collected
      using the critical incident technique, underwent content analysis. RESULTS:
      Planning of teaching, carrying out different stages of the simulation exercise,
      participant roles, and students' personal factors were central to learning
      interpersonal communication competence. CONCLUSION: Simulation is a valuable
      method in developing the interpersonal communication competence of students of
      health sciences at the masters' level. The methods used in the simulation
      teaching of emergency care are not necessarily applicable as such to
      communication education. The role of teacher is essential to supervising
      students' learning in simulation exercises. In the future, it is important to
      construct questions that help students to reflect specifically on communication.

PMID- 25567607
TI  - Heparin binding-epidermal growth factor-like growth factor for the regeneration
      of chronic tympanic membrane perforations in mice.
AB  - We aim to explore the role of epidermal growth factor (EGF) ligand shedding in
      tympanic membrane wound healing and to investigate the translation of its
      modulation in tissue engineering of chronic tympanic membrane perforations.
      Chronic suppurative otitis media (CSOM) is an infected chronic tympanic membrane
      perforation. Up to 200 million suffer from its associated hearing loss and it is
      the most common cause of pediatric hearing loss in developing countries. There is
      a need for nonsurgical treatment due to a worldwide lack of resources. In this
      study, we show that EGF ligand shedding is essential for tympanic membrane
      healing as it's inhibition, with KB-R7785, leads to chronic perforation in 87.9%
      (n=58) compared with 0% (n=20) of controls. We then show that heparin binding-EGF
      like growth factor (5 MUg/mL), which acts to shed EGF ligands, can regenerate
      chronic perforations in mouse models with 92% (22 of 24) compared with 38% (10 of
      26), also with eustachian tube occlusion with 94% (18 of 19) compared with 9% (2
      of 23) and with CSOM 100% (16 of 16) compared with 41% (7 of 17). We also show
      the nonototoxicity of this treatment and its hydrogel delivery vehicle. This
      provides preliminary data for a clinical trial where it could be delivered by
      nonspecialist trained healthcare workers and fulfill the clinical need for a
      nonsurgical treatment for chronic tympanic membrane perforation and CSOM.

PMID- 25567611
TI  - Innovative formulation of nystatin particulate systems in toothpaste for
      candidiasis treatment.
AB  - Oral candidiasis is a mycosis on the mucous membranes of the mouth but not
      limited to the mouth. Nystatin is one of the most frequently employed antifungal
      agents to treat infections and may be safely given orally as well as applied
      topically but its absorption through mucocutaneous membranes such as the gut and
      the skin is minimal. The purpose of this study is to enhance the effectiveness of
      nystatin using particulate system such as beads, micro- and nanoparticles of
      alginate incorporated into toothpaste. Those particulate systems of nystatin were
      prepared by extrusion/external gelation for beads and emulsification/internal
      gelation for micro- and nanoparticles and characterized. Small, anionic charged
      and monodispersed particles were successfully produced. The type of particulate
      system influenced all previous parameters, being microparticles the most suitable
      particulate system of nystatin showing the slowest release, the highest
      inhibitory effect of Candida albicans over a period of one year. Those results
      allowed the conclusion that alginate exhibits properties that enable the in vitro
      functionality of encapsulated nystatin and thus may provide the basis for new
      successful approaches for the treatment of oral antifungal infections such as
      oral candidiasis. 

PMID- 25567612
TI  - Weight gain in renal transplant recipients in a Polish single centre.
AB  - BACKGROUND: Excess weight is a risk factor for adverse cardiovascular events and
      affects patient and graft survival after renal transplantation (RT). The aim of
      the study was to measure the awareness of body mass index (BMI), overweight, and
      obesity, and to compare it with renal function, BMI, and obesity-related
      morbidities in renal transplant recipients (RTRs). MATERIAL AND METHODS: Fifty
      three randomly-selected RTRs completed a survey. The survey results were
      correlated to BMI and serum creatinine at 3 months after RT (+3), 1 year after RT
      (+12), at the moment of survey (+S), and to the incidences of new-onset diabetes
      after transplantation (NODAT) and arterial hypertension (AH). RESULTS: The time
      between (+3) and (+S) ranged from 1 to 20 years. The questionnaire revealed that
      61.8% of patients did not use BMI to evaluate their body mass, they did not
      distinguish between overweight and obesity, and only 40% of RTRs obtained
      information about obesity from physicians. At (+3), obesity was found in 9% and
      overweight in 27% of RTRs in comparison to 17% and 39% at (+S), respectively
      (p<0.05). Serum creatinine between (+3) and (+S) increased insignificantly in all
      patients regardless of their BMI. NODAT was found in 9.6% of RTRs and was
      diagnosed exclusively in the overweight group. There were no significant
      correlations between BMI and NODAT or AH incidences. CONCLUSIONS: BMI increases
      significantly after RT and is associated with higher risk of NODAT, but most RTRs
      are not aware of their BMI. Therefore, educational programs for this patient
      population should be created.

PMID- 25567613
TI  - Three-dimensional counting of morphologically normal human red blood cells via
      digital holographic microscopy.
AB  - Counting morphologically normal cells in human red blood cells (RBCs) is
      extremely beneficial in the health care field. We propose a three-dimensional (3
      D) classification method of automatically determining the morphologically normal
      RBCs in the phase image of multiple human RBCs that are obtained by off-axis
      digital holographic microscopy (DHM). The RBC holograms are first recorded by
      DHM, and then the phase images of multiple RBCs are reconstructed by a
      computational numerical algorithm. To design the classifier, the three typical
      RBC shapes, which are stomatocyte, discocyte, and echinocyte, are used for
      training and testing. Nonmain or abnormal RBC shapes different from the three
      normal shapes are defined as the fourth category. Ten features, including
      projected surface area, average phase value, mean corpuscular hemoglobin,
      perimeter, mean corpuscular hemoglobin surface density, circularity, mean phase
      of center part, sphericity coefficient, elongation, and pallor, are extracted
      from each RBC after segmenting the reconstructed phase images by using a
      watershed transform algorithm. Moreover, four additional properties, such as
      projected surface area, perimeter, average phase value, and elongation, are
      measured from the inner part of each cell, which can give significant information
      beyond the previous 10 features for the separation of the RBC groups; these are
      verified in the experiment by the statistical method of Hotelling's T-quare test.
      We also apply the principal component analysis algorithm to reduce the dimension
      number of variables and establish the Gaussian mixture densities using the
      projected data with the first eight principal components. Consequently, the
      Gaussian mixtures are used to design the discriminant functions based on Bayesian
      decision theory. To improve the performance of the Bayes classifier and the
      accuracy of estimation of its error rate, the leaving-one-out technique is
      applied. Experimental results show that the proposed method can yield good
      results for calculating the percentage of each typical normal RBC shape in a
      reconstructed phase image of multiple RBCs that will be favorable to the analysis
      of RBC-related diseases. In addition, we show that the discrimination performance
      for the counting of normal shapes of RBCs can be improved by using 3-D features
      of an RBC.

PMID- 25567614
TI  - Mini-invasive surgery of infratemporal fossa schwannomas.
AB  - BACKGROUND: Infratemporal fossa schwannomas are benign, encapsulated tumours of
      the trigeminal nerve limited to the infratemporal fossa. Because of the
      complications and significant morbidity associated with traditional surgical
      approaches to the infratemporal fossa, which include facial nerve dysfunction,
      hearing loss, dental malocclusion and cosmetic problems, less invasive
      alternatives have been sought. METHODS: This paper reports two cases of
      infratemporal fossa schwannomas treated in 2012 using mini-invasive approaches.
      The literature regarding different infratemporal fossa approaches was reviewed.
      RESULTS: The first schwannoma was 30 mm in size and was removed completely by a
      preauricular subtemporal approach. The second one was 25 mm in size and was
      removed completely using a purely transnasal endoscopic approach. In both cases,
      there were no intra-operative or post-operative complications. CONCLUSION: These
      two approaches allow non-invasive and wide exposure of the infratemporal fossa as
      compared to classical approaches. Surgical approach should be selected according
      to the tumour's anatomical location with respect to the maxillary sinus posterior
      wall. The preauricular subtemporal approach is recommended for tumours localised
      posterolaterally with respect to the maxillary sinus posterior wall. Medial and
      anterior tumours near the maxillary sinus posterior wall can be best removed
      using a transnasal endoscopic approach.

PMID- 25567615
TI  - Risk of cancer incidence before the age of 15 years after exposure to ionising
      radiation from computed tomography: results from a German cohort study.
AB  - The aim of this cohort study was to assess the risk of developing cancer,
      specifically leukaemia, tumours of the central nervous system and lymphoma,
      before the age of 15 years in children previously exposed to computed tomography
      (CT) in Germany. Data for children with at least one CT between 1980 and 2010
      were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010
      were identified by stochastic linkage with the German Childhood Cancer Registry
      (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed
      to assess the underlying medical conditions at time of the CT. Cases were only
      included if diagnosis occurred at least 2 years after the first CT and no signs
      of cancer were recorded in the radiology reports. Standardised incidence ratios
      (SIR) using incidence rates from the general population were estimated. The
      cohort included information on 71,073 CT examinations in 44,584 children
      contributing 161,407 person-years at risk with 46 cases initially identified
      through linkage with the GCCR. Seven cases had to be excluded due to signs
      possibly suggestive of cancer at the time of first CT. Overall, more cancer cases
      were observed (O) than expected (E), but this was mainly driven by unexpected and
      possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was
      1.72 (95 % CI 0.89-3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI
      0.54-2.78, O = 7). Despite careful examination of the medical information,
      confounding by indication or reverse causation cannot be ruled out completely and
      may explain parts of the excess. Furthermore, the CT exposure may have been
      underestimated as only data from the participating clinics were available. This
      should be taken into account when interpreting risk estimates. 

PMID- 25567617
TI  - Child interests in assisted reproductive technology: how is the welfare principle
      applied in practice?
AB  - STUDY QUESTION: How is the welfare principle interpreted and practised and what
      meaning does it hold for health professionals who must apply it in assisted
      reproductive technology (ART)? SUMMARY ANSWER: The welfare of a child is a
      meaningful concept to ART counsellors but it is also impractical when applied
      preconception. WHAT IS KNOWN ALREADY: Policy which promotes the interests of a
      child to be born is inconsistent between and within countries, and has been
      widely criticized as meaningless, as an unfair imposition and for its lack of
      clarity and inconsistent translation to ART practice. STUDY DESIGN, SIZE,
      DURATION: We conducted a qualitative study of ART counsellors in Australia and
      New Zealand in 2012. This study took an inductive approach.
      PARTICIPANTS/MATERIALS, SETTING AND METHODS: Thirty-two counsellors (15
      psychologists and 17 social workers) participated in 6 focus groups. Vignettes
      were used to focus and stimulate discussion of how the welfare of all
      participants but especially the interests of a non-existent child were
      interpreted and operationalized in practice. Qualitative descriptive content
      analysis was used to analyse the data into themes. MAIN RESULTS AND THE ROLE OF
      CHANCE: Five themes emerged in the data: giving presence to the child that could
      be, balancing welfare interests, welfare concerns, balancing values and making a
      decision and screening and legal presumptions against treatment. Themes were
      validated according to qualitative research standards. The study showed that
      counsellors take the child welfare principle seriously but that the concept is
      indeed slippery and difficult to operationalize. Counsellors denied a role in
      screening patients for parenting fitness but were engaged in health care
      assessment of patients and these roles need further differentiation, clarity and
      research. Health care practitioners would benefit from a process that reviews
      decisions and clarifies professional values. LIMITATIONS, REASONS FOR CAUTION:
      Participants were drawn from only two of the six Australian states and two
      territories. WIDER IMPLICATIONS OF THE FINDINGS: The study provides insight and
      deeper understanding of how welfare principles play out in counselling practice,
      what gives them meaning and the difficulties of balancing various interests and
      values. Our findings have shown that the welfare of a child can be a meaningful
      concept to ART counsellors but that it can also be impractical and unclear.
      Despite differences in legislation among countries, our study contributes to the
      growing data and debate emerging from the USA and the UK. STUDY FUNDING/COMPETING
      INTERESTS: This study was funded by a Flinders University Faculty of Health
      Sciences Grant. There are no conflicts of interest. TRIAL REGISTRATION NUMBER:
      Not applicable.

PMID- 25567616
TI  - Maternal exposure to perfluorinated chemicals and reduced fecundity: the MIREC
      study.
AB  - STUDY QUESTION: What is the effect of maternal exposure to perfluorooctane
      sulfonate (PFOS), perflurooctanoic acid (PFOA) and perfluorohexane sulfonate
      (PFHxS) on female fecundity? SUMMARY ANSWER: Increasing concentrations of PFOA or
      PFHxS in maternal plasma were associated with reduced fecundability and
      infertility. WHAT IS KNOWN ALREADY: Perfluorinated chemicals (PFCs) are a group
      of synthetic compounds used in industrial production. There is a concern about
      the effect of PFCs on fecundity, as measured by time-to-pregnancy (TTP). Although
      some recent studies suggest that increasing concentrations of PFCs may decrease
      fecundity, divergence in the methodological approaches used to evaluate this
      association have prevented firm conclusions being reached. STUDY DESIGN, SIZE,
      DURATION: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study
      is a cohort study of 2,001 women recruited before 14 weeks of gestation in 10
      cities across Canada between 2008 and 2011. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: A questionnaire was administered and medical chart data and biospecimens
      were collected from participants. After excluding women who withdrew, those for
      whom data were incomplete, those whose pregnancies followed birth control
      failure, and accounting for male fertility, 1743 participants remained. TTP was
      defined as the number of months of unprotected intercourse needed to become
      pregnant in the current pregnancy, as self-reported in the first trimester of
      pregnancy. Plasma concentrations of PFOA, PFOS and PFHxS measured in the first
      trimester were considered as a surrogate of preconception exposure. Fecundability
      odds ratios (FORs) were estimated using Cox proportional hazard models for
      discrete time. FOR < 1 denote a longer TTP and FORs >1 denote a shorter TTP. The
      odds of infertility (TTP > 12 months or infertility treatment in the index
      pregnancy) were estimated using logistic regression. Each chemical concentration
      (ng/ml) was log-transformed and divided by its SD. MAIN RESULTS AND THE ROLE OF
      CHANCE: The cumulative probabilities of pregnancy at 1, 6 and 12 months were 0.42
      (95% confidence interval (CI) 0.40-0.45), 0.81 (95% CI 0.79-0.83) and 0.90 (95%
      CI 0.89-0.92), respectively. The mean maternal age was 32.8 (SD 5.0) years. The
      geometric means (ng/ml) of PFOA, PFOS and PFHxS were 1.66 (95% CI 1.61-1.71),
      4.59 (95% CI 4.46-4.72) and 1.01 (95% CI 0.97-1.05), respectively. After
      adjustment for potential confounders, PFOA and PFHxS were associated with a 11
      and 9% reduction in fecundability per one SD increase (FOR = 0.89; 95% CI 0.83
      0.94; P < 0.001 for PFOA and FOR = 0.91; 95% CI 0.86-0.97; P = 0.002 for PFHxS),
      while no significant association was observed for PFOS (FOR = 0.96; 95% CI 0.91
      1.02; P = 0.17). In addition, the odds of infertility increased by 31% per one SD
      increase of PFOA (odds ratio (OR) = 1.31; 95% CI 1.11-1.53; P = 0.001) and by 27%
      per one SD increase of PFHxS (OR = 1.27; 95% CI 1.09-1.48; P = 0.003), while no
      significant association was observed for PFOS (OR = 1.14; 95% CI 0.98-1.34; P =
      0.09). LIMITATIONS, REASONS FOR CAUTION: Women with the highest concentrations of
      PFCs might have been excluded from the study if there is a causal association
      with infertility. The MIREC study did not assess concentrations of PFCs in males,
      semen quality, menstrual cycle characteristics or intercourse frequency. WIDER
      IMPLICATIONS OF THE FINDINGS: Our results add to the evidence that exposure to
      PFOA and PFHxS, even at lower levels than previously reported, may reduce
      fecundability. STUDY FUNDING/COMPETING INTERESTS: The MIREC study is supported by
      the Chemicals Management Plan of Health Canada, the Canadian Institutes for
      Health Research (CIHR, grant no. MOP - 81285) and the Ontario Ministry of the
      Environment. M.P.V. was supported by a CIHR Fellowship Award, and a CIHR-Quebec
      Training Network in Perinatal Research (QTNPR) Ph.D. scholarship. W.D.F. is
      supported by a CIHR Canada Research Chair. There are no conflicts of interest to
      declare.

PMID- 25567618
TI  - Successful fertility preservation following ovarian tissue vitrification in
      patients with primary ovarian insufficiency.
AB  - STUDY QUESTION: Is ovarian tissue cryopreservation using vitrification followed
      by in vitro activation (IVA) of dormant follicles a potential approach for
      infertility treatment of patients with primary ovarian insufficiency (POI)?
      SUMMARY ANSWER: Our vitrification approach followed by IVA treatment is a
      potential infertility therapy for POI patients whose ovaries contain residual
      follicles. WHAT IS KNOWN ALREADY: Akt (protein kinase B) stimulators [PTEN
      (phosphatase with TENsin homology deleted in chromosome 10) inhibitor and
      phosphatidyinositol-3-kinase (PI3 kinase) stimulator] activate dormant primordial
      follicles in vitro and ovarian fragmentation disrupts the Hippo signaling
      pathway, leading to the promotion of follicle growth. We treated POI patients
      with a combination of ovarian vitrification, fragmentation and drug treatment,
      followed by auto-transplantation, and reported successful follicle growth and
      pregnancies. STUDY DESIGN, SIZE, DURATION: Prospective clinical study of 37
      infertile women with POI between 12 August 2011 and 1 November 2013. We enrolled
      10 new patients since the previous publication. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: POI patients were originally selected based on a history of amenorrhea
      for more than 1 year and elevated serum FSH levels of >40 mIU/ml (n = 31) but
      this was later changed to >4 months, age <40 years and serum FSH levels of >35
      mIU/ml (n = 6) (mean 71.8 +/- 30.8, range 35.5-197.6) so as to include patients
      with a shorter duration of amenorrhea. Under laparoscopic surgery, ovariectomy
      was performed and ovarian cortices were dissected into strips for vitrification.
      Some pieces were examined histologically. After warming, two to three strips were
      fragmented into smaller cubes before culturing with Akt stimulators for 2 days.
      After washing, ovarian cubes were transplanted beneath the serosa of Fallopian
      tubes under laparoscopic surgery. Follicle growth was monitored by ultrasound and
      serum estrogen levels. After oocyte retrieval from mature follicles, IVF was
      performed. MAIN RESULTS AND THE ROLE OF CHANCE: Among 37 patients, 54% had
      residual follicles based on histology. Among patients with follicles, 9 out of 20
      showed follicle growth in auto-grafts with 24 oocytes retrieved from six
      patients. Following IVF and embryo transfer into four patients, three pregnancies
      were detected based on serum hCG, followed by one miscarriage and two successful
      deliveries. For predicting IVA success, we found that routine histological
      analyses of ovarian cortices and shorter duration from initial POI diagnosis to
      ovariectomy are valid parameters. LIMITATIONS, REASONS FOR CAUTION: Although our
      findings suggest that the present vitrification protocol is effective for ovarian
      tissue cryopreservation, we have not compared the potential of vitrification and
      slow freezing in follicle growth after grafting. We chose the serosa of Fallopian
      tubes as the auto-grating site due to its high vascularity and the ease to
      monitor follicle growth. Future studies are needed to evaluate the best auto
      grafting sites for ovarian tissues. Also, future studies are needed to identify
      biological markers to indicate the presence of residual follicles in POI to
      predict IVA treatment outcome. WIDER IMPLICATIONS OF THE FINDINGS: In POI
      patients, ovarian reserve, namely the pool of residual follicles, continues to
      diminish with age. If one ovary is cryopreserved at an earlier stage of POI,
      patients could undergo additional non-invasive infertility treatments before the
      final decision for the IVA treatment. Furthermore, in the cases of unmarried POI
      patients, cryopreservation of ovarian tissues allows their fertility preservation
      until they desire to bear children. STUDY FUNDING/COMPETING INTERESTS: This work
      was supported by Grant-In-Aid for Scientific Research (Research B: 24390376,
      Challenging Exploratory Research: 24659722, and Innovative Areas, Mechanisms
      regulating gamete formation in animals: 26114510) and by research funds from the
      Smoking Research Foundation, and the Takeda Science Foundation. None of the
      authors has a conflict of interest. TRIAL REGISTRATION NUMBER: UMIN000010828.

PMID- 25567620
TI  - Current smoking is associated with lower seminal vesicles and ejaculate volume,
      despite higher testosterone levels, in male subjects of infertile couples.
AB  - STUDY QUESTION: What is the impact of smoking behaviour on seminal, hormonal and
      male genital tract ultrasound parameters in subjects seeking medical care for
      couple infertility? STUDY ANSWER: In males of infertile couples, current smokers
      (CS), when compared with non-smokers, show lower ejaculate and ultrasound-derived
      seminal vesicles (SV) volume, despite higher testosterone levels. WHAT IS KNOWN
      ALREADY: Data on the effects of smoking on male fertility are conflicting. A
      correlation between smoking and reduced semen parameters has been reported,
      however, with a high heterogeneity among studies. An association between smoking
      behaviour and higher testosterone levels in men has been described in several,
      but not all, the previous studies. No study has systematically evaluated the
      impact of smoking on the male genital tract ultrasound characteristics. STUDY
      DESIGN, SIZE AND DURATION: Retrospective cross-sectional analysis of a
      consecutive series of 426 subjects seeking medical care for couple infertility
      from January 2010 to July 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: From
      the entire cohort, 394 men (age 36.0 +/- 8.0 years) free of genetic abnormalities
      were selected. All subjects underwent a complete andrological and physical
      examination, biochemical and hormonal assessment, scrotal and transrectal colour
      Doppler ultrasound and semen analysis (including seminal interleukin-8 levels,
      sIL-8) within the same day. MAIN RESULTS AND THE ROLE OF CHANCE: Among the
      patients evaluated, 229 were never smokers (NS), 56 past smokers (PS) and 109 CS.
      When CS were compared with the rest of the sample (non-smokers, NS + PS), in a
      multivariate model (analysis of covariance, ANCOVA) adjusted for age, lifestyle
      (including alcohol, cannabis and physical activity), BMI and sex hormone-binding
      globulin, significantly higher androgen (total testosterone, P = 0.001;
      calculated free testosterone, P < 0.005) and lower FSH (P < 0.05) levels were
      observed in CS. However, when total testosterone was also included in the
      multivariate model as a further covariate, the difference in FSH levels was not
      confirmed. In a similar model, a lower ejaculate volume (P < 0.01) and a higher
      prevalence of normal sperm morphology (P < 0.02) were also detected in CS in
      comparison with the rest of the sample. However, when total testosterone was also
      included in the multivariate model as a further covariate, only the difference in
      ejaculate volume between CS and non-smokers was confirmed (-0.61 +/- 0.23 ml, P <
      0.01). Finally, CS showed lower total SV volume, before and after ejaculation,
      even after adjusting for confounders (P = 0.02 and <0.01, respectively). Similar
      results were observed when the reported number of cigarettes smoked or the number
      of pack-years was considered separately. LIMITATIONS, REASONS FOR CAUTION: The
      present results are derived from patients consulting an Andrology Clinic for
      couple infertility, who could have different characteristics from the general
      male population or males consulting general practitioners for reasons other than
      couple infertility. In addition, we did not have a true control group composed of
      age-matched, apparently healthy, fertile men, and therefore true normative data
      of sonographic parameters cannot be inferred. Due to the cross-sectional nature
      of our study, neither a causality hypothesis nor mechanistic models can be drawn.
      Finally, this is a retrospective study, and further prospective studies are
      required. WIDER IMPLICATIONS OF THE FINDINGS: We report an apparent paradox in
      CS: lower SV volume despite higher testosterone levels. Our data suggest that
      smoking may negatively affect SV volume in an independent manner, as the
      difference between CS and non-smokers retained significance after adjusting for
      confounders including testosterone. This is the first study reporting such
      ultrasound evidence. How this new smoking-related alteration, along with low
      semen volume, impacts male fertility needs to be addressed by further studies.
      STUDY FUNDING/COMPETING INTERESTS: No funding was received for the study. None of
      the authors have any conflict of interest to declare.

PMID- 25567619
TI  - Direct actions of androgens on the survival, growth and secretion of steroids and
      anti-Mullerian hormone by individual macaque follicles during three-dimensional
      culture.
AB  - STUDY QUESTION: What are the direct effects of androgens on primate follicular
      development and function at specific stages of folliculogenesis? SUMMARY ANSWER:
      Androgen addition altered primate follicle survival, growth, steroid and anti
      Mullerian hormone (AMH) production, and oocyte quality in vitro, in a dose- and
      stage-dependent manner. WHAT IS KNOWN ALREADY: Androgens have local actions in
      the ovary, particularly in the developing follicles. It is hypothesized that
      androgen promotes early follicular growth, but becomes detrimental to the antral
      follicles in primates. STUDY DESIGN, SIZE, DURATION: In vitro follicle maturation
      was performed using rhesus macaques. Secondary (125-225 um) follicles were
      mechanically isolated from 14 pairs of ovaries, encapsulated into alginate (0.25%
      w/v), and cultured for 40 days. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Individual follicles were cultured in a 5% O2 environment, in alpha minimum
      essential medium supplemented with recombinant human FSH. Follicles were randomly
      assigned to experiments of steroid ablation by trilostane (TRL), testosterone (T)
      replacement and dihydrotestosterone (DHT) replacement. Follicle survival and
      growth were assessed. Follicles with diameters >=500 MUm at Week 5 were
      categorized as fast-grow follicles. Pregnenolone (P5), progesterone (P4),
      estradiol (E2) and AMH concentrations in media were measured. Meiotic maturation
      and fertilization of oocytes from recombinant human chorionic gonadotrophin
      treated follicles were assessed at the end of culture. MAIN RESULTS AND THE ROLE
      OF CHANCE: Compared with controls, TRL exposure reduced (P < 0.05) follicle
      survival, antrum formation rate and follicle diameters at Week 5. While P5
      concentrations increased (P < 0.05) following TRL treatment, P4 levels decreased
      (P < 0.05) in fast-grow follicles at Week 5. Few healthy oocytes were retrieved
      from antral follicles developed in the presence of TRL. T replacement with TRL
      increased (P < 0.05) follicle survival and antrum formation at Week 5, compared
      with TRL alone, to levels comparable to controls. However, high-dose T with TRL
      decreased (P < 0.05) diameters of fast-grow follicles. Although P4 concentrations
      produced by fast-grow follicles were not altered by T in the presence of TRL,
      there was a dose-dependent increase (P < 0.05) in E2 levels at Week 5. High-dose
      T with TRL decreased (P < 0.05) AMH production by fast-grow follicles at Week 3.
      More healthy oocytes were retrieved from antral follicles developed in TRL+T
      compared with TRL alone. DHT had the similar effects to those of high-dose T,
      except that DHT replacement decreased (P < 0.05) E2 concentrations produced by
      fast-grow follicles at Week 5 regardless of TRL treatment. LIMITATION, REASONS
      FOR CAUTION: This study reports T and DHT actions on in vitro-developed
      individual primate (macaque) follicles, which are limited to the interval from
      the secondary to small antral stage. WIDER IMPLICATION OF THE FINDINGS: The above
      findings provide novel information on the role(s) of androgens in primate
      follicular development and oocyte maturation. We hypothesize that androgens
      promote pre-antral follicle development, but inhibit antral follicle growth and
      function in primates. While androgens can act positively, excess levels of
      androgens may have negative impacts on primate folliculogenesis. STUDY
      FUNDING/COMPETING INTERESTS: NIH U54 RR024347/RL1HD058294/PL1EB008542
      (Oncofertility Consortium), NIH U54 HD071836 (SCCPIR), NIH ORWH/NICHD
      2K12HD043488 (BIRCWH), NIH FIC TW/HD-00668, ONPRC 8P51OD011092. There are no
      conflicts of interest.

PMID- 25567621
TI  - Developmental kinetics of cleavage stage mouse embryos are related to their
      subsequent carbohydrate and amino acid utilization at the blastocyst stage.
AB  - STUDY QUESTION: What is the relationship between cleavage stage embryo kinetics,
      blastocyst metabolism and subsequent embryo viability? SUMMARY ANSWER: Embryos
      cleaving faster at the first cleavage division resulted in blastocysts with a
      larger inner cell mass (ICM), higher glucose consumption, lower glycolytic rate,
      higher aspartate uptake, lower global amino acid turnover and higher percentage
      of developing fetuses on E13.5 when compared with blastocysts that developed from
      slower cleaving embryos. WHAT IS KNOWN ALREADY: Previous research has shown that
      morphokinetics, blastocyst carbohydrate metabolism and cleavage stage amino acid
      metabolism of the preimplantation embryo can be used independently as markers of
      its developmental competence and subsequent viability. STUDY DESIGN, SIZE,
      DURATION: Morphokinetics of in vitro fertilized mouse zygotes were observed using
      a time-lapse imaging system and they were identified as 'fast' or 'slow' cleaving
      embryos. Spent culture media from resultant blastocysts were analysed for
      carbohydrate and amino acid utilization. Blastocysts either had their ICM and
      trophectoderm (TE) cell number determined, were cultured further in an outgrowth
      assay or transferred to a recipient female to assess implantation and fetal
      development. PARTICIPANTS/MATERIALS, SETTING, METHODS: Morphokinetics of in vitro
      fertilized C57BL/6xCBA (F1) zygotes individually cultured in 2 ul drops of G1/G2
      media with HSA under Ovoil in 5% O2, 6% CO2 and 89% N2 were analysed using a time
      lapse incubator. At 72 h post-insemination, blastocysts were separated into
      quartiles derived from timing of the first cleavage division. Blastocysts were
      cultured for a further 24 h and spent media samples, including controls
      containing no embryos, were frozen and subsequently analysed for amino acid
      utilization using liquid chromatography-mass spectrometry. These blastocysts were
      then analysed over a further 1.5 h period for carbohydrate utilization and
      subsequently stained to determine ICM and TE cells. To analyse implantation
      potential, fetal quality and viability, additional 'fast' and 'slow' blastocysts
      were cultured further in an outgrowth model or transferred to recipient females.
      MAIN RESULTS AND THE ROLE OF CHANCE: Embryos cleaving faster at the time of first
      cleavage (first quartile, designated 'fast') were on average 2.5 h ahead of
      slower embryos (fourth quartile, designated 'slow', 15.1 +/- 0.1 versus 17.6 +/-
      0.1 h, P < 0.001). On Day 5 of culture, blastocysts developed from 'fast' embryos
      had a larger ICM number (17.4 +/- 2.1 versus 7.4 +/- 2.0, P < 0.01), a higher
      glucose consumption (21.2 +/- 1.2 versus 14.3 +/- 1.0 pmol/embryo/h, P < 0.001)
      and a lower glycolytic rate (expressed as the percentage of glucose converted to
      lactate) (49.6 +/- 2.8 versus 59.7 +/- 2.8%, P < 0.05) compared with 'slow'
      embryos. Further non-invasive metabolomic analysis revealed that 'fast'
      blastocysts consumed more aspartate (2.2 +/- 0.1 versus 1.8 +/- 0.1
      pmol/embryo/h, P < 0.05) and produced little or no glutamate compared with 'slow'
      blastocysts (0.02 +/- 0.07 consumed versus 0.32 +/- 0.11 pmol/embryo/h produced,
      P < 0.05). Transfer of 'fast' blastocysts to pseudo-pregnant recipients resulted
      in higher fetal survival post-implantation compared with 'slow' blastocysts (69.6
      versus 40.4%, P < 0.01). LIMITATIONS, REASONS FOR CAUTION: The timing of the
      first cleavage division was used to classify blastocysts as 'fast' or 'slow'
      embryos; however, a combination of several developmental kinetic markers
      (cleavage time of 3- to 8-cell, duration between cleavage division times) may be
      used to more accurately determine an embryo as 'fast' or 'slow'. Only the fastest
      and slowest quartiles (those embryos with the fastest and slowest first cleavage
      division) were analysed in this study. WIDER IMPLICATIONS OF THE FINDINGS: These
      findings show that kinetically different embryos develop into blastocysts with
      different metabolic profiles and viability. Work is now being undertaken to
      determine if using these viability markers in combination will increase embryo
      selection efficacy and further improve implantation and pregnancy rates. STUDY
      FUNDING/COMPETING INTERESTS: The study was funded by the University of Melbourne.
      The authors have no conflicts of interest to declare.

PMID- 25567622
TI  - Minimally invasive surgery when treating endometriosis has a positive effect on
      health and on quality of work life of affected women.
AB  - STUDY QUESTION: What is the effect of the minimally invasive surgical treatment
      of endometriosis on health and on quality of work life (e.g. working performance)
      of affected women? SUMMARY ANSWER: Absence from work, performance loss and the
      general negative impact of endometriosis on the job are reduced significantly by
      the laparoscopic surgery. WHAT IS KNOWN ALREADY: The benefits of surgery overall
      and of the laparoscopic method in particular for treating endometriosis have been
      described before. However, previous studies focus on medical benchmarks without
      including the patient's perspective in a quantitative manner. STUDY DESIGN, SIZE,
      DURATION: A retrospective questionnaire-based survey covering 211 women with
      endometriosis and a history of specific laparoscopic surgery in a Swiss
      university hospital, tertiary care center. Data were returned anonymously and
      were collected from the beginning of 2012 until March 2013.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Women diagnosed with endometriosis and
      with at least one specific laparoscopic surgery in the past were enrolled in the
      study. The study investigated the effect of the minimally invasive surgery on
      health and on quality of work life of affected women. Questions used were
      obtained from the World Endometriosis Research Foundation (WERF) Global Study on
      Women's Health (GSWH) instrument. The questionnaire was shortened and adapted for
      the purpose of the present study. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 587
      women invited to participate in the study, 232 (232/587 = 40%) returned the
      questionnaires. Twenty-one questionnaires were excluded due to incomplete data
      and 211 sets (211/587 = 36%) were included in the study. Our data show that 62%
      (n = 130) of the study population declared endometriosis as influencing the job
      during the period prior to surgery, compared with 28% after surgery (P < 0.001).
      The mean (maximal) absence from work due to endometriosis was reduced from 2.0
      (4.9) to 0.5 (1.4) hours per week (P < 0.001). The mean (maximal) loss in working
      performance after the surgery averaged out at 5.7% (12.6%) compared with 17.5%
      (30.5%) before this treatment (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The
      mediocre response rate of the study weakens the representativeness of the
      investigated population. Considering the anonymous setting a non-responder
      investigation was not performed. A bias due to selection, information and
      negativity effects within a retrospective survey cannot be excluded, although
      study-sensitive questions were provided in multiple ways. The absence of a
      control group (sham group; e.g. patients undergoing specific diagnostic
      laparoscopy without treatment) is a further limitation of the study. WIDER
      IMPLICATIONS OF THE FINDINGS: Our study shows that indicated minimally invasive
      surgery has a clear positive effect on the wellbeing and working performance of
      women suffering from moderate to severe endometriosis. Furthermore, national net
      savings in indirect costs with the present number of surgeries is estimated to be
      ?10.7 million per year. In an idealized setting (i.e. without any diagnosis
      delay) this figure could be more than doubled. STUDY FUNDING/COMPETING INTERESTS:
      The study was performed on behalf of the University Hospital of Bern
      (Inselspital) as one of the leading Swiss tertiary care centers. The authors do
      not declare any competing interests.

PMID- 25567625
TI  - Special Issue: Evolutionary perspectives on salmonid conservation and management.
AB  - This special issue of Evolutionary Applications comprises 15 papers that
      illustrate how evolutionary principles can inform the conservation and management
      of salmonid fishes. Several papers address the past evolutionary history of
      salmonids to gain insights into their likely plastic and genetic responses to
      future environmental change. The remaining papers consider potential evolutionary
      responses to climate warming, biological invasions, artificial propagation,
      habitat alteration, and harvesting. All of these papers consider how such
      influences might alter selective regimes, which should then favour plastic or
      genetic responses. Some of the papers then go on to document such responses, at
      least some of which are genetically based and adaptive. Despite the different
      approaches and target species, all of the papers argue for the importance of
      evolutionary considerations in the conservation and management of salmonids. 

PMID- 25567623
TI  - Saccharomyces cerevisiae as a model for the study of extranuclear functions of
      mammalian telomerase.
AB  - The experimental evidence from the last decade made telomerase a prominent member
      of a family of moonlighting proteins performing different functions at various
      cellular loci. However, the study of extratelomeric functions of the catalytic
      subunit of mammalian telomerase (TERT) is often complicated by the fact that it
      is sometimes difficult to distinguish them from its role(s) at the chromosomal
      ends. Here, we present an experimental model for studying the extranuclear
      function(s) of mammalian telomerase in the yeast Saccharomyces cerevisiae. We
      demonstrate that the catalytic subunit of mammalian telomerase protects the yeast
      cells against oxidative stress and affects the stability of the mitochondrial
      genome. The advantage of using S. cerevisiae to study of mammalian telomerase is
      that (1) mammalian TERT does not interfere with its yeast counterpart in the
      maintenance of telomeres, (2) yeast telomerase is not localized in mitochondria
      and (3) it does not seem to be involved in the protection of cells against
      oxidative stress and stabilization of mtDNA. Thus, yeast cells can be used as a
      'test tube' for reconstitution of mammalian TERT extranuclear function(s). 

PMID- 25567626
TI  - Evolutionary history of Pacific salmon in dynamic environments.
AB  - Contemporary evolution of Pacific salmon (Oncorhynchus spp.) is best viewed in
      the context of the evolutionary history of the species and the dynamic ecosystems
      they inhabit. Speciation was complete by the late Miocene, leaving c. six million
      years for intraspecific diversification. Following the most recent glacial
      maximum, large areas became available for recolonization. Current intraspecific
      diversity is thus the product of recent evolution overlaid onto divergent
      historical lineages forged during recurrent episodes of Pleistocene glaciation.
      In northwestern North America, dominant habitat features have been relatively
      stable for the past 5000 years, but salmon ecosystems remain dynamic because of
      disturbance regimes (volcanic eruptions, landslides, wildfires, floods,
      variations in marine and freshwater productivity) that occur on a variety of
      temporal and spatial scales. These disturbances both create selective pressures
      for adaptive responses by salmon and inhibit long-term divergence by periodically
      extirpating local populations and creating episodic dispersal events that erode
      emerging differences. Recent anthropogenic changes are replicated pervasively
      across the landscape and interrupt processes that allow natural habitat recovery.
      If anthropogenic changes can be shaped to produce disturbance regimes that more
      closely mimic (in both space and time) those under which the species evolved,
      Pacific salmon should be well-equipped to deal with future challenges, just as
      they have throughout their evolutionary history. 

PMID- 25567627
TI  - Recurrent evolution of life history ecotypes in sockeye salmon: implications for
      conservation and future evolution.
AB  - We examine the evolutionary history and speculate about the evolutionary future
      of three basic life history ecotypes that contribute to the biocomplexity of
      sockeye salmon (Oncorhynchus nerka). The 'recurrent evolution' (RE) hypothesis
      claims that the sea/river ecotype is ancestral, a 'straying' form with poorly
      differentiated (meta)population structure, and that highly structured populations
      of lake-type sockeye and kokanee have evolved repeatedly in parallel adaptive
      radiations between recurrent glaciations of the Pleistocene Epoch. Basic premises
      of this hypothesis are consistent with new, independent evidence from recent
      surveys of genetic variation in mitochondrial and microsatellite DNA: (1) sockeye
      salmon are most closely related to pink (O. gorbuscha) and chum (O. keta) salmon
      with sea-type life histories; (2) the sockeye life history ecotypes exist as
      polyphyletic lineages within large drainages and geographic regions; (3) the
      sea/river ecotype exhibits less genetic differentiation among populations than
      the lake or kokanee ecotypes both within and among drainages; and (4) genetic
      diversity is typically higher in the sea/river ecotype than in the lake and
      kokanee ecotypes. Anthropogenic modification of estuarine habitat and intensive
      coastal fisheries have likely reduced and fragmented historic metapopulations of
      the sea/river ecotype, particularly in southern areas. In contrast, the kokanee
      ecotype appears to be favoured by marine fisheries and predicted changes in
      climate. 

PMID- 25567624
TI  - Genetics and underlying pathology of dementia.
AB  - As the population steadily ages, dementia, in all its forms, remains a great
      societal challenge. Yet, our knowledge of their etiology remains rather limited.
      To this end, genetic studies can give us insight into the underlying mechanisms
      that lead to the development of dementia, potentially facilitating treatments in
      the future. In this review we cover the most recent genetic risk factors
      associated with the onset of the four most common dementia types today, including
      Alzheimer's disease (AD), Vascular Dementia (VaD), Frontotemporal Lobar
      Degeneration (FTLD) and Lewy Body Dementia (LBD). Moreover, we discuss the
      overlap in major underlying pathologies of dementia derived from their genetic
      associations. While all four dementia types appear to involve genes associated
      with tau-pathology and neuroinflammation only LBD, AD and VaD appear to involve
      amyloid genes while LBD and FTLD share alpha synuclein genes. Together these
      findings suggest that some of the dementias may exist along a spectrum and
      demonstrates the necessity to conduct large-scale studies pinpointing the
      etiology of the dementias and potential gene and environment interactions that
      may influence their development. 

PMID- 25567628
TI  - A review of quantitative genetic components of fitness in salmonids: implications
      for adaptation to future change.
AB  - Salmonine fishes are commonly subjected to strong, novel selective pressures due
      to anthropogenic activities and global climate change, often resulting in
      population extinction. Consequently, there is considerable interest in predicting
      the long-term evolutionary trajectories of extant populations. Knowledge of the
      genetic architecture of fitness traits is integral to making these predictions.
      We reviewed the published, peer-reviewed literature for estimates of heritability
      and genetic correlation for fitness traits in salmonine fishes with two broad
      goals in mind: summarization of published data and testing for differences among
      categorical variables (e.g., species, life history type, experimental
      conditions). Balanced coverage of variables was lacking and estimates for wild
      populations and behavioral traits were nearly absent. Distributions of
      heritability estimates were skewed toward low values and distributions of genetic
      correlations toward large, positive values, suggesting that significant potential
      for evolution of traits exists. Furthermore, experimental conditions had a direct
      effect on h (2) estimates, and other variables had more complex effects on h (2)
      and r G estimates, suggesting that available estimates may be insufficient for
      use in models to predict evolutionary change in wild populations. Given this and
      other inherent complicating factors, making accurate predictions of the
      evolutionary trajectories of salmonine fishes will be a difficult task. 

PMID- 25567629
TI  - Adaptive landscapes and density-dependent selection in declining salmonid
      populations: going beyond numerical responses to human disturbance.
AB  - Theory suggests an important role for population density in shaping adaptive
      landscapes through density-dependent selection. Here, we identify five
      methodological approaches for studying such selection, review the existing
      empirical evidence for it, and ask whether current declines in abundance can be
      expected to trigger evolutionary responses in salmonid fishes. Across taxa we
      find substantial amounts of evidence for population density influencing the
      location of adaptive peaks for a range of traits, and, in the presence of
      frequency dependence, changing the shape of selection (stabilizing versus
      disruptive). For salmonids, biological and theoretical considerations suggest
      that the optimal value of a number of traits associated with juvenile competitive
      ability (e.g. egg size, timing of emergence from nests, dominance ability), may
      depend on population density. For adults, more direct experimental and
      comparative evidence suggest that secondary sexual traits can be subject to
      density-dependent selection. There is also evidence that density affects the
      frequency-dependent selection likely responsible for the expression of
      alternative male reproductive phenotypes in salmon. Less is known however about
      the role of density in maintaining genetic variation among juveniles. Further
      efforts are required to elucidate the indirect evolutionary effects of declining
      population abundances, both in salmonids and in other anthropogenically
      challenged organisms. 

PMID- 25567630
TI  - Potential responses to climate change in organisms with complex life histories:
      evolution and plasticity in Pacific salmon.
AB  - Salmon life histories are finely tuned to local environmental conditions, which
      are intimately linked to climate. We summarize the likely impacts of climate
      change on the physical environment of salmon in the Pacific Northwest and discuss
      the potential evolutionary consequences of these changes, with particular
      reference to Columbia River Basin spring/summer Chinook (Oncorhynchus
      tshawytscha) and sockeye (Oncorhynchus nerka) salmon. We discuss the possible
      evolutionary responses in migration and spawning date egg and juvenile growth and
      development rates, thermal tolerance, and disease resistance. We know little
      about ocean migration pathways, so cannot confidently suggest the potential
      changes in this life stage. Climate change might produce conflicting selection
      pressures in different life stages, which will interact with plastic (i.e.
      nongenetic) changes in various ways. To clarify these interactions, we present a
      conceptual model of how changing environmental conditions shift phenotypic optima
      and, through plastic responses, phenotype distributions, affecting the force of
      selection. Our predictions are tentative because we lack data on the strength of
      selection, heritability, and ecological and genetic linkages among many of the
      traits discussed here. Despite the challenges involved in experimental
      manipulation of species with complex life histories, such research is essential
      for full appreciation of the biological effects of climate change. 

PMID- 25567631
TI  - Potential for anthropogenic disturbances to influence evolutionary change in the
      life history of a threatened salmonid.
AB  - Although evolutionary change within most species is thought to occur slowly,
      recent studies have identified cases where evolutionary change has apparently
      occurred over a few generations. Anthropogenically altered environments appear
      particularly open to rapid evolutionary change over comparatively short time
      scales. Here, we consider a Pacific salmon population that may have experienced
      life-history evolution, in response to habitat alteration, within a few
      generations. Historically, juvenile fall Chinook salmon (Oncorhynchus
      tshawytscha) from the Snake River migrated as subyearlings to the ocean. With
      changed riverine conditions that resulted from hydropower dam construction, some
      juveniles now migrate as yearlings, but more interestingly, the yearling
      migration tactic has made a large contribution to adult returns over the last
      decade. Optimal life-history models suggest that yearling juvenile migrants
      currently have a higher fitness than subyearling migrants. Although phenotypic
      plasticity likely accounts for some of the change in migration tactics, we
      suggest that evolution also plays a significant role. Evolutionary change
      prompted by anthropogenic alterations to the environment has general implications
      for the recovery of endangered species. The case study we present herein
      illustrates the importance of integrating evolutionary considerations into
      conservation planning for species at risk. 

PMID- 25567632
TI  - Big dams and salmon evolution: changes in thermal regimes and their potential
      evolutionary consequences.
AB  - Dams designed for hydropower and other purposes alter the environments of many
      economically important fishes, including Chinook salmon (Oncorhynchus
      tshawytscha). We estimated that dams on the Rogue River, the Willamette River,
      the Cowlitz River, and Fall Creek decreased water temperatures during summer and
      increased water temperatures during fall and winter. These thermal changes
      undoubtedly impact the behavior, physiology, and life histories of Chinook
      salmon. For example, relatively high temperatures during the fall and winter
      should speed growth and development, leading to early emergence of fry.
      Evolutionary theory provides tools to predict selective pressures and genetic
      responses caused by this environmental warming. Here, we illustrate this point by
      conducting a sensitivity analysis of the fitness consequences of thermal changes
      caused by dams, mediated by the thermal sensitivity of embryonic development.
      Based on our model, we predict Chinook salmon likely suffered a decrease in mean
      fitness after the construction of a dam in the Rogue River. Nevertheless, these
      demographic impacts might have resulted in strong selection for compensatory
      strategies, such as delayed spawning by adults or slowed development by embryos.
      Because the thermal effects of dams vary throughout the year, we predict dams
      impacted late spawners more than early spawners. Similar analyses could shed
      light on the evolutionary consequences of other environmental perturbations and
      their interactions. 

PMID- 25567633
TI  - Evolutionary consequences of habitat loss for Pacific anadromous salmonids.
AB  - Large portions of anadromous salmonid habitat in the western United States has
      been lost because of dams and other blockages. This loss has the potential to
      affect salmonid evolution through natural selection if the loss is biased,
      affecting certain types of habitat differentially, and if phenotypic traits
      correlated with those habitat types are heritable. Habitat loss can also affect
      salmonid evolution indirectly, by reducing genetic variation and changing its
      distribution within and among populations. In this paper, we compare the
      characteristics of lost habitats with currently accessible habitats and review
      the heritability of traits which show correlations with habitat/environmental
      gradients. We find that although there is some regional variation, inaccessible
      habitats tend to be higher in elevation, wetter and both warmer in the summer and
      colder in the winter than habitats currently available to anadromous salmonids.
      We present several case studies that demonstrate either a change in phenotypic or
      life history expression or an apparent reduction in genetic variation associated
      with habitat blockages. These results suggest that loss of habitat will alter
      evolutionary trajectories in salmonid populations and Evolutionarily Significant
      Units. Changes in both selective regime and standing genetic diversity might
      affect the ability of these taxa to respond to subsequent environmental
      perturbations. Both natural and anthropogenic and should be considered seriously
      in developing management and conservation strategies. 

PMID- 25567634
TI  - Changes in selection and evolutionary responses in migratory brown trout
      following the construction of a fish ladder.
AB  - Brown trout (Salmo trutta) are extensively harvested and its habitat highly
      influenced by human encroachments. Using a 40-year time series of mark-recapture
      data we estimate vital rates for a piscivorous trout population. This population
      spawns upstream of a waterfall, which historically acted as a migration barrier
      for smaller trout. In 1966, the waterfall was dammed and a fish ladder
      constructed. All fish ascending the fish ladder were individually tagged and
      measured for a variety of traits. The fish ladder overall favoured access to
      upstream spawning areas for middle-sized trout, resulting in stabilizing
      selection acting on size at spawning. Over time, natural and fishing mortality
      have varied, with fishing mortality generally decreasing and natural mortality
      increasing. The average and, particularly, variance in size-at-first-spawning,
      and growth rates during the first years of lake residence have all decreased over
      the 1966-2003 period. These changes are all consistent with a shift from
      directional to stabilizing selection on age and size at spawning. Estimated rates
      of phenotypic change are relatively high, in particular for size at first
      spawning, adding further support for the growing notion that human interference
      may lead to rapid life-history trait evolution. 

PMID- 25567635
TI  - Rapid natural selection for resistance to an introduced parasite of rainbow
      trout.
AB  - Introduced species and infectious diseases both independently pose challenges for
      the preservation of existing biodiversity. However, native species or disease
      hosts are by no means 'unarmed' when faced with novel environmental challenges,
      provided that adequate adaptive genetic variation exists to mount effective
      evolutionary responses. In this study, we examined the consequences of the
      recently introduced parasite and causative agent of whirling disease (Myxobolus
      cerebralis) in a wild rainbow trout (Oncorhynchus mykiss) population from
      Harrison Lake, Montana (USA). Consistent with the parasite's age-specific
      effects, juvenile rainbow trout recruitment into Harrison Lake was substantially
      reduced following parasite detection in 1995. However, experimental data suggest
      that natural selection has rapidly reduced whirling disease susceptibility within
      the population over time. The rapid observed temporal change in resistance
      patterns argues that the standing genetic variation for parasite resistance
      facilitated this process. Our findings ultimately underscore the importance of
      preserving genetic diversity to ensure that species of economic importance or of
      conservation concern have maximal chances for persistence in future changing
      environments. 

PMID- 25567636
TI  - Fitness of hatchery-reared salmonids in the wild.
AB  - Accumulating data indicate that hatchery fish have lower fitness in natural
      environments than wild fish. This fitness decline can occur very quickly,
      sometimes following only one or two generations of captive rearing. In this
      review, we summarize existing data on the fitness of hatchery fish in the wild,
      and we investigate the conditions under which rapid fitness declines can occur.
      The summary of studies to date suggests: nonlocal hatchery stocks consistently
      reproduce very poorly in the wild; hatchery stocks that use wild, local fish for
      captive propagation generally perform better than nonlocal stocks, but often
      worse than wild fish. However, the data above are from a limited number of
      studies and species, and more studies are needed before one can generalize
      further. We used a simple quantitative genetic model to evaluate whether
      domestication selection is a sufficient explanation for some observed rapid
      fitness declines. We show that if selection acts on a single trait, such rapid
      effects can be explained only when selection is very strong, both in captivity
      and in the wild, and when the heritability of the trait under selection is high.
      If selection acts on multiple traits throughout the life cycle, rapid fitness
      declines are plausible. 

PMID- 25567637
TI  - Evolutionary effects of alternative artificial propagation programs: implications
      for viability of endangered anadromous salmonids.
AB  - Most hatchery programs for anadromous salmonids have been initiated to increase
      the numbers of fish for harvest, to mitigate for habitat losses, or to increase
      abundance in populations at low abundance. However, the manner in which these
      programs are implemented can have significant impacts on the evolutionary
      trajectory and long-term viability of populations. In this paper, we review the
      potential benefits and risks of hatchery programs relative to the conservation of
      species listed under the US Endangered Species Act. To illustrate, we present the
      range of potential effects within a population as well as among populations of
      Chinook salmon (Oncorhynchus tshawytscha) where changes to major hatchery
      programs are being considered. We apply evolutionary considerations emerging from
      these examples to suggest broader principles for hatchery uses that are
      consistent with conservation goals. We conclude that because of the evolutionary
      risks posed by artificial propagation programs, they should not be viewed as a
      substitute for addressing other limiting factors that prevent achieving
      viability. At the population level, artificial propagation programs that are
      implemented as a short-term approach to avoid imminent extinction are more likely
      to achieve long-term population viability than approaches that rely on long-term
      supplementation. In addition, artificial propagation programs can have out-of
      population impacts that should be considered in conservation planning. 

PMID- 25567638
TI  - Increase in maturation size after the closure of a high seas gillnet fishery on
      hatchery-reared chum salmon Oncorhynchus keta.
AB  - Gillnet fisheries are strongly size-selective and seem to produce changes in size
      at maturity for exploited fishes. After Word War II, large-scale gillnet
      fisheries targeted Pacific salmon (Oncorhynchus spp.) in the high seas area of
      the North Pacific and the Bering Sea, but these fisheries were closed in 1993. To
      assess the effects of this high seas gillnet fishery (and its closing) on size at
      maturity, we examined long-term trends in size at 50% probability of maturing
      (L50) for chum salmon (O. keta) from three populations in Hokkaido, Japan. The
      L50 trends were statistically different among rivers, but showed similar temporal
      patterns with decreases in the 1970s and early 1980s and increases after the 1985
      brood year. While fishery-induced evolution seemed largely responsible for this
      temporal change in L50 during the fishing period, natural selection and
      phenotypic plasticity induced by environmental changes could contribute to the
      increases in L50 after the relaxation of fishing pressure. 

PMID- 25567639
TI  - Evolutionary consequences of fishing and their implications for salmon.
AB  - We review the evidence for fisheries-induced evolution in anadromous salmonids.
      Salmon are exposed to a variety of fishing gears and intensities as immature or
      maturing individuals. We evaluate the evidence that fishing is causing
      evolutionary changes to traits including body size, migration timing and age of
      maturation, and we discuss the implications for fisheries and conservation. Few
      studies have fully evaluated the ingredients of fisheries-induced evolution:
      selection intensity, genetic variability, correlation among traits under
      selection, and response to selection. Most studies are limited in their ability
      to separate genetic responses from phenotypic plasticity, and environmental
      change complicates interpretation. However, strong evidence for selection
      intensity and for genetic variability in salmon fitness traits indicates that
      fishing can cause detectable evolution within ten or fewer generations.
      Evolutionary issues are therefore meaningful considerations in salmon fishery
      management. Evolutionary biologists have rarely been involved in the development
      of salmon fishing policy, yet evolutionary biology is relevant to the long-term
      success of fisheries. Future management might consider fishing policy to (i)
      allow experimental testing of evolutionary responses to exploitation and (ii)
      improve the long-term sustainability of the fishery by mitigating unfavorable
      evolutionary responses to fishing. We provide suggestions for how this might be
      done. 

PMID- 25567640
TI  - The impact of fishing-induced mortality on the evolution of alternative life
      history tactics in brook charr.
AB  - Although contemporary trends indicative of evolutionary change have been detected
      in the life-history traits of exploited populations, it is not known to what
      extent fishing influences the evolution of alternative life-history tactics in
      migratory species such as salmonids. Here, we build a model to predict the
      evolution of anadromy and residency in an exploited population of brook charr,
      Salvelinus fontinalis. Our model allows for both phenotypic plasticity and
      genetic change in the age and size at migration by including migration reaction
      norms. Using this model, we predict that fishing of anadromous individuals over
      the course of 100 years causes evolution in the migration reaction norm,
      resulting in a decrease in average probabilities of migration with increasing
      harvest rate. Moreover, we show that differences in natural mortalities in
      freshwater greatly influence the magnitude and rate of evolutionary change. The
      fishing-induced changes in migration predicted by our model alter population
      abundances and reproductive output and should be accounted for in the sustainable
      management of salmonids. 

PMID- 25567641
TI  - Echogenic perfluorohexane-loaded macrophages adhere in vivo to activated vascular
      endothelium in mice, an explorative study.
AB  - BACKGROUND: Macrophages may concentrate ultrasound contrast agents and exhibit
      selective adhesion to activated endothelium. The present study investigates in
      mice the potential of perfluorohexane (PFH) loaded macrophages to act as
      ultrasound contrast agent with high reflectivity and specifically targeted at
      (atherosclerotic) vascular lesions. METHODS: Lung passage was evaluated with a
      mouse echo scanner after injection, at a slow pace or as a bolus, of varying
      doses of PFH-loaded and unloaded bone marrow macrophages (BMM) into the jugular
      vein. The interaction of PFH-loaded and unloaded BMM with TNF-alpha stimulated
      carotid artery endothelium after tail vein injection was assessed by means of
      intravital microscopy. RESULTS: High doses of jugular vein injected PFH-loaded
      BMM were visible with ultrasound in the pulmonary artery and detectable in the
      carotid artery. At intravital microscopy, tail vein injected BMM exhibited
      rolling and adhesion behavior at the TNF-alpha stimulated carotid endothelium,
      similar to that of native blood leukocytes. Rolling behavior was not different
      between PFH-loaded and unloaded BMM (p = 0.38). CONCLUSION: In vivo,
      perfluorohexane loaded macrophages pass the pulmonary circulation and appear on
      the arterial side. Moreover, they roll and adhere selectively to activated
      endothelium under physiological flow conditions. These findings indicate that
      perfluorohexane loaded BMM could be used to study processes in vivo where
      endothelial activation plays a role, such as atherosclerosis.

PMID- 25567642
TI  - A novel single-layered MoS2 nanosheet based microfluidic biosensor for
      ultrasensitive detection of DNA.
AB  - Recently, MoS2 nanosheets were demonstrated to be able to spontaneously adsorb
      single-stranded DNA, acting as efficient dye quenchers. We herein report a novel
      microfluidic biosensor for fluorescent DNA detection based on single-layered MoS2
      nanosheets. The proposed platform is simple, rapid and visible with high
      sensitivity and selectivity. 

PMID- 25567643
TI  - Synthesis of graphene-supported one-dimensional nanoporous Pt based catalysts,
      and their enhanced performance on methanol electro-oxidation.
AB  - A novel approach is developed to synthesize PtIr or Pt nanowires (NWs) supported
      on the reduced graphene oxide (RGO) using Te NWs as template based on the
      replacement reaction. The resulting RGO-supported PtIr and Pt electrocatalysts
      are characterized by transmission electron microscopy (TEM), energy-dispersive x
      ray spectroscopy and electrochemical techniques. TEM images show that these Pt
      based catalysts are uniformly distributed in the matrix of graphene with a
      characteristic of one-dimensional (1D) nanoporous structure. As one of promising
      anode materials used in the direct methanol fuel cells, these 1D nanoporous
      PtIr/RGO (or Pt/RGO) hybrids exhibit an enlarged electroactive surface and
      enhanced catalytic activity toward the methanol reaction relative to those PtIr
      or Pt NWs without graphene support. 

PMID- 25567644
TI  - Avoiding tipping points in fisheries management through Gaussian process dynamic
      programming.
AB  - Model uncertainty and limited data are fundamental challenges to robust
      management of human intervention in a natural system. These challenges are
      acutely highlighted by concerns that many ecological systems may contain tipping
      points, such as Allee population sizes. Before a collapse, we do not know where
      the tipping points lie, if they exist at all. Hence, we know neither a complete
      model of the system dynamics nor do we have access to data in some large region
      of state space where such a tipping point might exist. We illustrate how a
      Bayesian non-parametric approach using a Gaussian process (GP) prior provides a
      flexible representation of this inherent uncertainty. We embed GPs in a
      stochastic dynamic programming framework in order to make robust management
      predictions with both model uncertainty and limited data. We use simulations to
      evaluate this approach as compared with the standard approach of using model
      selection to choose from a set of candidate models. We find that model selection
      erroneously favours models without tipping points, leading to harvest policies
      that guarantee extinction. The Gaussian process dynamic programming (GPDP)
      performs nearly as well as the true model and significantly outperforms standard
      approaches. We illustrate this using examples of simulated single-species
      dynamics, where the standard model selection approach should be most effective
      and find that it still fails to account for uncertainty appropriately and leads
      to population crashes, while management based on the GPDP does not, as it does
      not underestimate the uncertainty outside of the observed data. 

PMID- 25567645
TI  - Scaling of phloem structure and optimality of photoassimilate transport in
      conifer needles.
AB  - The phloem vascular system facilitates transport of energy-rich sugar and
      signalling molecules in plants, thus permitting long-range communication within
      the organism and growth of non-photosynthesizing organs such as roots and fruits.
      The flow is driven by osmotic pressure, generated by differences in sugar
      concentration between distal parts of the plant. The phloem is an intricate
      distribution system, and many questions about its regulation and structural
      diversity remain unanswered. Here, we investigate the phloem structure in the
      simplest possible geometry: a linear leaf, found, for example, in the needles of
      conifer trees. We measure the phloem structure in four tree species representing
      a diverse set of habitats and needle sizes, from 1 (Picea omorika) to 35 cm
      (Pinus palustris). We show that the phloem shares common traits across these four
      species and find that the size of its conductive elements obeys a power law. We
      present a minimal model that accounts for these common traits and takes into
      account the transport strategy and natural constraints. This minimal model
      predicts a power law phloem distribution consistent with transport energy
      minimization, suggesting that energetics are more important than translocation
      speed at the leaf level. 

PMID- 25567646
TI  - Solar activity at birth predicted infant survival and women's fertility in
      historical Norway.
AB  - Ultraviolet radiation (UVR) can suppress essential molecular and cellular
      mechanisms during early development in living organisms and variations in solar
      activity during early development may thus influence their health and
      reproduction. Although the ultimate consequences of UVR on aquatic organisms in
      early life are well known, similar studies on terrestrial vertebrates, including
      humans, have remained limited. Using data on temporal variation in sunspot
      numbers and individual-based demographic data (N = 8662 births) from Norway
      between 1676 and 1878, while controlling for maternal effects, socioeconomic
      status, cohort and ecology, we show that solar activity (total solar irradiance)
      at birth decreased the probability of survival to adulthood for both men and
      women. On average, the lifespans of individuals born in a solar maximum period
      were 5.2 years shorter than those born in a solar minimum period. In addition,
      fertility and lifetime reproductive success (LRS) were reduced among low-status
      women born in years with high solar activity. The proximate explanation for the
      relationship between solar activity and infant mortality may be an effect of
      folate degradation during pregnancy caused by UVR. Our results suggest that solar
      activity at birth may have consequences for human lifetime performance both
      within and between generations. 

PMID- 25567647
TI  - Temperature variability and moisture synergistically interact to exacerbate an
      epizootic disease.
AB  - Climate change is altering global patterns of precipitation and temperature
      variability, with implications for parasitic diseases of humans and wildlife. A
      recent study confirmed predictions that increased temperature variability could
      exacerbate disease, because of lags in host acclimation following temperature
      shifts. However, the generality of these host acclimation effects and the
      potential for them to interact with other factors have yet to be tested. Here, we
      report similar effects of host thermal acclimation (constant versus shifted
      temperatures) on chytridiomycosis in red-spotted newts (Notophthalmus
      viridescens). Batrachochytrium dendrobatidis (Bd) growth on newts was greater
      following a shift to a new temperature, relative to newts already acclimated to
      this temperature (15 degrees C versus 25 degrees C). However, these acclimation
      effects depended on soil moisture (10, 16 and 21% water) and were only observed
      at the highest moisture level, which induced greatly increased Bd growth and
      infection-induced mortality. Acclimation effects were also greater following a
      decrease rather than an increase in temperature. The results are consistent with
      previous findings that chytridiomycosis is associated with precipitation, lower
      temperatures and increased temperature variability. This study highlights host
      acclimation as a potentially general mediator of climate-disease interactions,
      and the need to account for context-dependencies when testing for acclimation
      effects on disease. 

PMID- 25567648
TI  - Speed kills: ineffective avian escape responses to oncoming vehicles.
AB  - Animal-vehicle collisions cause high levels of vertebrate mortality worldwide,
      and what goes wrong when animals fail to escape and ultimately collide with
      vehicles is not well understood. We investigated alert and escape behaviours of
      captive brown-headed cowbirds (Molothrus ater) in response to virtual vehicle
      approaches of different sizes and at speeds ranging from 60 to 360 km h(-1).
      Alert and flight initiation distances remained similar across vehicle speeds, and
      accordingly, alert and flight initiation times decreased at higher vehicle
      speeds. Thus, avoidance behaviours in cowbirds appeared to be based on distance
      rather than time available for escape, particularly at 60-150 km h(-1); however,
      at higher speeds (more than or equal to 180 km h(-1)) no trend in response
      behaviour was discernible. As vehicle speed increased, cowbirds did not have
      enough time to assess the approaching vehicle, and cowbirds generally did not
      initiate flight with enough time to avoid collision when vehicle speed exceeded
      120 km h(-1). Although potentially effective for evading predators, the decision
      making process used by cowbirds in our study appears maladaptive in the context
      of avoiding fast-moving vehicles. Our methodological approach and findings
      provide a framework to assess how novel management strategies could affect escape
      rules, and the sensory and cognitive abilities animals use to avoid vehicle
      collisions. 

PMID- 25567649
TI  - Specialization and group size: brain and behavioural correlates of colony size in
      ants lacking morphological castes.
AB  - Group size in both multicellular organisms and animal societies can correlate
      with the degree of division of labour. For ants, the task specialization
      hypothesis (TSH) proposes that increased behavioural specialization enabled by
      larger group size corresponds to anatomical specialization of worker brains.
      Alternatively, the social brain hypothesis proposes that increased levels of
      social stimuli in larger colonies lead to enlarged brain regions in all workers,
      regardless of their task specialization. We tested these hypotheses in acacia
      ants (Pseudomyrmex spinicola), which exhibit behavioural but not morphological
      task specialization. In wild colonies, we marked, followed and tested ant workers
      involved in foraging tasks on the leaves (leaf-ants) and in defensive tasks on
      the host tree trunk (trunk-ants). Task specialization increased with colony size,
      especially in defensive tasks. The relationship between colony size and brain
      region volume was task-dependent, supporting the TSH. Specifically, as colony
      size increased, the relative size of regions within the mushroom bodies of the
      brain decreased in trunk-ants but increased in leaf-ants; those regions play
      important roles in learning and memory. Our findings suggest that workers
      specialized in defence may have reduced learning abilities relative to leaf-ants;
      these inferences remain to be tested. In societies with monomorphic workers,
      brain polymorphism enhanced by group size could be a mechanism by which division
      of labour is achieved. 

PMID- 25567650
TI  - Ventrolateral and dorsomedial frontal cortex lesions impair mnemonic context
      retrieval.
AB  - The prefrontal cortex appears to contribute to the mnemonic retrieval of the
      context within which stimuli are experienced, but only under certain conditions
      that remain to be clarified. Patients with lesions to the frontal cortex, the
      temporal lobe and neurologically intact individuals were tested for context
      memory retrieval when verbal stimuli (words) had been experienced across multiple
      (unstable context condition) or unique (stable context condition) contexts; basic
      recognition memory of these words-in-contexts was also tested. Patients with
      lesions to the right ventrolateral prefrontal cortex (VLPFC) were impaired on
      context retrieval only when the words had been seen in multiple contexts,
      demonstrating that this prefrontal region is critical for active retrieval
      processing necessary to disambiguate memory items embedded across multiple
      contexts. Patients with lesions to the left dorsomedial prefrontal region were
      impaired on both context retrieval conditions, regardless of the stability of the
      stimulus-to-context associations. Conversely, prefrontal lesions sparing the
      ventrolateral and dorsomedial regions did not impair context retrieval. Only
      patients with temporal lobe excisions were impaired on basic recognition memory.
      The results demonstrate a basic contribution of the left dorsomedial frontal
      region to mnemonic context retrieval, with the VLPFC engaged, selectively, when
      contextual relations are unstable and require disambiguation. 

PMID- 25567651
TI  - Functional identity and diversity of animals predict ecosystem functioning better
      than species-based indices.
AB  - Drastic biodiversity declines have raised concerns about the deterioration of
      ecosystem functions and have motivated much recent research on the relationship
      between species diversity and ecosystem functioning. A functional trait framework
      has been proposed to improve the mechanistic understanding of this relationship,
      but this has rarely been tested for organisms other than plants. We analysed
      eight datasets, including five animal groups, to examine how well a trait-based
      approach, compared with a more traditional taxonomic approach, predicts seven
      ecosystem functions below- and above-ground. Trait-based indices consistently
      provided greater explanatory power than species richness or abundance. The
      frequency distributions of single or multiple traits in the community were the
      best predictors of ecosystem functioning. This implies that the ecosystem
      functions we investigated were underpinned by the combination of trait identities
      (i.e. single-trait indices) and trait complementarity (i.e. multi-trait indices)
      in the communities. Our study provides new insights into the general mechanisms
      that link biodiversity to ecosystem functioning in natural animal communities and
      suggests that the observed responses were due to the identity and dominance
      patterns of the trait composition rather than the number or abundance of species
      per se. 

PMID- 25567652
TI  - Gradual acquisition of immunity to severe malaria with increasing exposure.
AB  - Previous analyses have suggested that immunity to non-cerebral severe malaria due
      to Plasmodium falciparum is acquired after only a few infections, whereas
      longitudinal studies show that some children experience multiple episodes of
      severe disease, suggesting that immunity may not be acquired so quickly. We
      fitted a mathematical model for the acquisition and loss of immunity to severe
      disease to the age distribution of severe malaria cases stratified by symptoms
      from a range of transmission settings in Tanzania, combined with data from
      several African countries on the age distribution and overall incidence of severe
      malaria. We found that immunity to severe disease was acquired more gradually
      with exposure than previously thought. The model also suggests that physiological
      changes, rather than exposure, may alter the symptoms of disease with increasing
      age, suggesting that a later age at infection would be associated with a higher
      proportion of cases presenting with cerebral malaria regardless of exposure. This
      has consequences for the expected pattern of severe disease as transmission
      changes. Careful monitoring of the decline in immunity associated with reduced
      transmission will therefore be needed to ensure rebound epidemics of severe and
      fatal malaria are avoided. 

PMID- 25567653
TI  - Childhood neurodevelopmental problems and adolescent bully victimization:
      population-based, prospective twin study in Sweden.
AB  - Bully victimization is a common problem among children with neurodevelopmental
      disorders, including attention deficit/hyperactivity disorder and autism spectrum
      disorder. Previous research was mostly cross-sectional and seldom accounted for
      co-morbid psychopathology, which makes it difficult to draw conclusions about
      causality and specificity of any association. Using a genetically informative
      prospective design, we investigated the association between various
      neurodevelopmental problems (NDPs) in childhood and bully victimization in
      adolescence, and the relative contributions of genetic and environmental factors
      to this association. We obtained parent-reports of NDPs at age 9/12 years and
      self-reported bully victimization at age 15 for 3,921 children participating in
      the The Child and Adolescent Twin Study in Sweden (CATSS). Structural equation
      modelling was used to control for NDP co-morbidity and bully victimization at
      baseline. Cholesky decomposition was used to analyse genetic and environmental
      contributions to observed associations. Because most of the NDPs were associated
      to later bully victimization, a common effect of all NDPs was summarized into a
      general NDP factor. Controlling for this general factor, only problems with
      social interaction and motor control uniquely predicted subsequent bully
      victimization in girls. General and unique associations were influenced by both
      genetic and unique environmental factors. NDPs in general and social interaction
      and motor problems in particular predicted later bully victimization. The
      longitudinal design and twin analyses indicated that these associations might be
      causal. Knowledge of these vulnerabilities may be important when designing risk
      assessment and prevention strategies. 

PMID- 25567655
TI  - Sorcin Enhances Metastasis and Promotes Epithelial-to-Mesenchymal Transition of
      Colorectal Cancer.
AB  - Sorcin, a soluble resistance-related calcium-binding protein, belongs to the
      small penta-EF-hand family. Recent study reported that upregulation of sorcin
      correlated with metastasis and poor prognosis of colorectal cancer (CRC). In the
      present study, we explored the regulatory role of sorcin in CRC metastasis. To
      investigate the role of sorcin in CRC metastasis, sorcin overexpressed with empty
      vector as control in CRC cell line (HCT116). The effect of sorcin overexpression
      on cell migration and invasion was evaluated via wound healing and transwell
      assay, respectively. Sorcin-induced changes in EMT process were evaluated by
      estern blot. Furthermore, the role of PI3K/Akt in the regulatory effect of sorcin
      on cell migration and invasion, and EMT process was explored by suppressing Akt
      activity in sorcin-overexpressed HCT116 cells. Sorcin overexpression in HCT116
      cells resulted in a significant increase in cell migration and invasion. Sorcin
      overexpression also markedly promoted the EMT process. More importantly, our
      results revealed that sorcin stimulated EMT process through activating PI3K/Akt
      signaling. In summary, this study indicated that the promoting effect of sorcin
      on CRC metastasis was, at least in part, through PI3K/Akt signaling. The findings
      in this study highlight the effectiveness and therapeutic potential to utilize
      sorcin-targeted strategies in the treatment of CRC. 

PMID- 25567654
TI  - Screening for rheumatic heart disease: evaluation of a focused cardiac ultrasound
      approach.
AB  - BACKGROUND: Rheumatic heart disease (RHD) remains a major public health problem
      worldwide. Although early diagnosis by echocardiography may potentially play a
      key role in developing active surveillance, systematic evaluation of simple
      approaches in resource poor settings are needed. METHODS AND RESULTS: We
      prospectively compared focused cardiac ultrasound (FCU) to a reference approach
      for RHD screening in a school children population. FCU included (1) the use of a
      pocket-sized echocardiography machine, (2) nonexpert staff (2 nurses with
      specific training), and (3) a simplified set of echocardiographic criteria. The
      reference approach used standardized echocardiographic examination, reviewed by
      an expert cardiologist, according to 2012 World Heart Federation criteria. Among
      the 6 different echocardiographic criteria, first tested in a preliminary phase,
      mitral regurgitation jet length>=2 cm or any aortic regurgitation was considered
      best suited to be FCU criteria. Of the 1217 subjects enrolled (mean, 9.6+/-1
      years; 49.6% male), 49 (4%) were diagnosed with RHD by the reference approach.
      The sensitivity of FCU for the detection of RHD was 83.7% (95% confidence
      interval, 73.3-94.0) for nurse A and 77.6% (95% confidence interval, 65.9-89.2)
      for nurse B. FCU yielded a specificity of 90.9% (95% confidence interval, 89.3
      92.6) and 92.0% (95% confidence interval, 90.4-93.5) according to users.
      Percentage of agreement among nurses was 91.4%. CONCLUSIONS: FCU by nonexperts
      using pocket devices seems feasible and yields acceptable sensitivity and
      specificity for RHD detection when compared with the state-of-the-art approach,
      thereby opening new perspectives for mass screening for RHD in low-resource
      settings.

PMID- 25567656
TI  - The Use of Limited Fluid Resuscitation and Blood Pressure-Controlling Drugs in
      the Treatment of Acute Upper Gastrointestinal Hemorrhage Concomitant with
      Hemorrhagic Shock.
AB  - The aim of this study was to evaluate the usefulness of the limited fluid
      resuscitation regimen combined with blood pressure-controlling drugs in treating
      acute upper gastrointestinal hemorrhage concomitant with hemorrhagic shock. A
      total of 51 patients were enrolled and divided into a group that received
      traditional fluid resuscitation group (conventional group, 24 patients) and a
      limited fluid resuscitation group (study group, 27 patients). Before and after
      resuscitation, the blood lactate, base excess, and hemoglobin values, as well as
      the volume of fluid resuscitation and resuscitation time were examined. Compared
      with conventional group, study group had significantly better values of blood
      lactate, base excess, and hemoglobin (all p < 0.05). In addition, both volume of
      fluid resuscitation and resuscitation time were significantly (p < 0.05) lower in
      these patients. Limited fluid resuscitation combined with blood pressure
      controlling drugs effectivelyxxx maintains blood perfusion of vital organs,
      improves whole body perfusion indicators, reduces the volume of fluid
      resuscitation, and achieves better bleeding control and resuscitation
      effectiveness. 

PMID- 25567657
TI  - Effectiveness of Olanzapine Combined with Ondansetron in Prevention of
      Chemotherapy-Induced Nausea and Vomiting of Non-small Cell Lung Cancer.
AB  - The objective of this study is to compare the effectiveness of olanzapine
      combined with ondansetron or ondansetron alone in preventing chemotherapy-induced
      nausea and vomiting (CINV) of non-small cell lung cancer (NSCLC). A total of 84
      NSCLC patients were equally randomized into intervention group and control group.
      Both groups were intravenously administered with ondansetron 8 mg 30 min before
      chemotherapy. In the intervention group, olanzapin 10 mg was orally administered
      for 8 days, beginning from the first morning of chemotherapy. The antiemetic
      effectiveness was evaluated in the first chemotherapy cycle. The incidence of
      acute vomiting was 33.33 % (14/42) and 54.76 % (23/42) in the intervention group
      and control group (p < 0.05) whereas that of delayed vomiting was 16.57 % (7/42)
      and 47.62 % (20/42) (p < 0.05). Compared with ondansetron alone, the combination
      of olanzapine with ondansetron has better effectiveness in preventing CINV in
      NSCLC patients, particularly for the delayed type. 

PMID- 25567658
TI  - Nursing Care of Lower Respiratory Tract Infection After Abdominal Surgery.
AB  - The harm, the causes, and nursing care methods of lower respiratory tract
      infection after abdominal operation were described in this article. 

PMID- 25567659
TI  - Influence of Nitroglycerin on Coronary Artery CT Imaging in Cardiovascular
      Diseases.
AB  - This study was designed to observe the influence of nitroglycerin on the quality
      of coronary artery imaging when CT is used for coronary heart disease. Data of
      150 cardiology inpatients were collected from Department of Cardiology of our
      hospital from November 2013 to August 2014 for this study. All the subjects were
      diagnosed with multislice CT and coronary angiography after admission. The
      patients were then divided into two groups, the nitroglycerin group of 75 cases
      who took nitroglycerin and the control group of 75 cases who took no
      nitroglycerin. A total of 320 mixed plaques (pathological characteristics of
      calcified ingredients and non-calcified ingredients), including 290 calcified
      mixed plaques of type I, (mainly with calcified plaques and purely calcified
      plaques), and 30 non-calcified plaques of type II, (mainly with non-calcified
      ingredients or pure non-calcified plaques) were scanned. CT coronary angiography
      showed that the detection rate of type I plaque was 65.5 % in control group and
      34.8 % in nitroglycerin group, whereas the detection rate of type II plaque was
      30 % in control group and 70 % in nitroglycerin group. The difference for both
      type I and type II was statistically significant (p < 0.05). In Comparison with
      control group, the increase in diameter of 1-13 vascular segments in
      nitroglycerin group was statistically significant (p < 0.05). Taking
      nitroglycerin can improve the display resolution of coronary angiography, and
      shows better display for type I than type II plaques. 

PMID- 25567660
TI  - Radiophotographically Controlled Nasointestinal Intubation to Treat Recurrent
      Postoperative Adhesive Ileus.
AB  - This study describes clinical experience and curative effect of
      radiophotographically controlled nasointestinal intubation in the treatment of
      small intestine arrangement in recurrent postoperative adhesive ileus. A 300-cm
      long nasointestinal tube was installed into the jejunum through the nasal cavity
      under radiophotographic observation in 25 patients with recurrent postoperative
      adhesive ileus. The tube was advanced into the ileum by enterokinesia to relieve
      adhesive ileus and conduct small bowel arrangement. Duration of tube installation
      was 13 +/- 11 min (range of 9-36 min). The success rate was 88 %. In 3 patients,
      assistance by a gastroscope was required. Twenty-one out of 25 patients were
      cured, making the cure rate of 84 %. The time for intestinal arrangement was 18.5
      +/- 3 days. The patients were followed up for 6 months to 2 years; there was 1
      case of recurrence, while other patients recovered smoothly with no recurrence. A
      non-surgical nasointestinal intubation under radiophotography is a simple, safe,
      and effective management with few complications and beneficial outcome in
      recurrent postoperative adhesive ileus. 

PMID- 25567661
TI  - Development of a fed-batch process for a recombinant Pichia pastoris Deltaoch1
      strain expressing a plant peroxidase.
AB  - Pichia pastoris is a prominent host for recombinant protein production, amongst
      other things due to its capability of glycosylation. However, N-linked glycans on
      recombinant proteins get hypermannosylated, causing problems in subsequent unit
      operations and medical applications. Hypermannosylation is triggered by an alpha
      1,6-mannosyltransferase called OCH1. In a recent study, we knocked out OCH1 in a
      recombinant P. pastoris CBS7435 Mut(S) strain (Deltaoch1) expressing the
      biopharmaceutically relevant enzyme horseradish peroxidase. We characterized the
      strain in the controlled environment of a bioreactor in dynamic batch
      cultivations and identified the strain to be physiologically impaired. We faced
      cell cluster formation, cell lysis and uncontrollable foam formation.In the
      present study, we investigated the effects of the 3 process parameters
      temperature, pH and dissolved oxygen concentration on 1) cell physiology, 2) cell
      morphology, 3) cell lysis, 4) productivity and 5) product purity of the
      recombinant Deltaoch1 strain in a multivariate manner. Cultivation at 30 degrees
      C resulted in low specific methanol uptake during adaptation and the risk of
      methanol accumulation during cultivation. Cell cluster formation was a function
      of the C-source rather than process parameters and went along with cell lysis. In
      terms of productivity and product purity a temperature of 20 degrees C was highly
      beneficial. In summary, we determined cultivation conditions for a recombinant P.
      pastoris Deltaoch1 strain allowing high productivity and product purity. 

PMID- 25567662
TI  - The effectiveness of RECIST on survival in patients with NSCLC receiving
      chemotherapy with or without target agents as first-line treatment.
AB  - We analyzed the correlation between survival and antitumor effect evaluated by
      RECIST in advanced NSCLC patients with chemotherapy plus target therapy or not as
      first-line treatment, to examine the applicability of RECIST in this population.
      The patients were screened from 4 clinical trials (12621, 12006, FASTACT-I, and
      FASTACT-II), and those who received chemotherapy plus target therapy or
      chemotherapy alone were eligible. Among the 59 enrolled patients, 29 received
      combination therapy, while the other 30 received chemotherapy only. In the
      combination therapy group, patients with PR or SD had longer overall survival
      (OS) than those with PD (P < 0.001 and P = 0.002, respectively). However, in the
      chemotherapy alone group, compared with PD patients, either PR or SD group had no
      significant overall survival benefit (P = 0.690 and P = 0.528, respectively). In
      summary, for advanced NSCLC patients receiving chemotherapy plus target therapy
      as first-line treatment and evaluated by RECIST criteria, SD has the same overall
      survival benefit as PR, suggesting that antitumor effective evaluation by RECIST
      criteria cannot be translated to overall survival benefit especially for this
      kind of patients. Therefore, developing a more comprehensive evaluation method to
      perfect RECIST criteria is thus warranted for patients received target therapy in
      NSCLC. 

PMID- 25567664
TI  - Excess of polonium-210 activity in the surface urban atmosphere. Part 2: origin
      of 210Po excess.
AB  - The presence of significant (210)Po activity, unsupported by its grandparent
      radionuclide (210)Pb, in the surface atmosphere of industrialized regions can
      originate from human technical activities. In urban air, the activity ratio of
      (210)Po to (210)Pb might increase as a result of natural condensation and
      coagulation processes of relatively volatile (210)Po-containing species emitted
      during coal combustion processes. The presence of excess of (210)Po cannot be
      explained by its in-growth from radioactive decay of (210)Bi. About 50% of
      (210)Po radionuclide released during coal combustion processes can be emitted
      into air as gaseous or ultrafine products. Subsequently, these products are
      quickly attached to the surface of fine particles suspended in the air. As a
      result, an excess of (210)Po activity in aerosols has been reported. However, in
      this manner, As much as 11 GBq of (210)Po per year can enter the urban air from
      the local coal power plants in Lodz city, Poland. 

PMID- 25567663
TI  - Perioperative and long-term outcome after standard pancreaticoduodenectomy,
      additional portal vein and multivisceral resection for pancreatic head cancer.
AB  - INTRODUCTION: The value of extended resection (portal vein, multivisceral) in
      patients with pancreatic adenocarcinoma (PDAC) is not well defined. We analyzed
      the outcome after standard resection (standard pancreaticoduodenectomy (SPR)),
      additional portal vein (PV) and multivisceral (MV) resection in PDAC patients.
      METHODS: Clinicopathologic, perioperative, and survival data of patients
      undergoing pancreatic head resection (PHR) for PDAC 1994-2014 were reviewed from
      a prospective database. RESULTS: Three hundred fifty nine patients had PHR for
      PDAC: 208 (58 %) underwent SPR, 131 (36 %) additional PV, and 20 (6 %) MV. The
      postoperative complication rate in MV (65 %) was slightly higher than in PV (56
      %) or SPR (50 %; p = 0.32). MV patients had higher in-hospital mortality (10 %)
      than SPR (3.8 %) and PV (1.5 %) patients (p = 0.12). Nodal status was comparable,
      whereas more patients in PV and MV had final R0 resection (p = 0.02). Five-year
      survival was 7 % after MV versus 17 % in patients without MV (p = 0.07).
      Multivariate survival analysis identified resection margin, nodal disease, blood
      transfusions, and MV are set as independent risk factors for overall survival.
      CONCLUSION: Multivisceral pancreatic head resections for PDAC are associated with
      increased perioperative morbidity and mortality, without improving oncologic
      outcome. Portal vein resection can be performed safely to reach R0 resection and
      its survival benefits.

PMID- 25567665
TI  - Adenosquamous carcinoma of the stomach and review of the literature.
AB  - Adenosquamous carcinoma of the stomach is a very rare disease, consisting of less
      than 0.4 % of all stomach cancer. From 1991 to 2013, a total of 2800 patients
      received gastrectomy for gastric cancer at Taipei Veterans General hospital.
      Among them, seven patients (0.25 %) diagnosed as adenosquamous carcinoma were
      enrolled. The clinicopathologic characteristics and prognosis were analyzed. The
      mean age of the seven patients was 62.3 years-old. There were 5 males and 2
      females. Six patients were stage III disease and one patient was stage IV
      disease. Four patients finally died of gastric cancer. Only one patient had no
      recurrence until death. Among the seven patients, adenocarcinoma component
      comprises the majority of the metastatic lymph node in 6 patients (85.7 %). The
      only one patient with major squamous cell carcinoma component in metastatic lymph
      node had no tumor recurrence till death. Adenosquamous carcinoma of stomach is a
      rare disease and is associated with a poor prognosis. The component of
      adenocarcinoma and squamous cell carcinoma in the metastatic lymph node may
      influence the prognosis.

PMID- 25567666
TI  - A self-assembled, pi-stacked complex as a finely-tunable magnetic aligner for
      biomolecular NMR applications.
AB  - The number of molecules constituting 1D intermolecular aggregates of the pi
      stacked self-assembled complex was controlled by altering the concentration and
      temperature. Enhanced magnetic orientation was observed for the aggregates with
      larger aggregation numbers. It was demonstrated that the designable complex
      aggregates serve as magnetic aligners to induce magnetic alignment upon an
      analyte protein coexisting in the solution, resulting in the observation of
      residual dipolar coupling (RDC) of the analyte. 

PMID- 25567668
TI  - Photo-controlled targeted intracellular delivery of both nitric oxide and singlet
      oxygen using a fluorescence-trackable ruthenium nitrosyl functional nanoplatform.
AB  - A multifunctional nitric oxide (NO) delivery nanoplatform that combines
      functionalities of target directing, fluorescence tracking, and photo-controlled
      target attacking was developed. The {Ru-NO@TiO2 NPs} nanoplatform selectively
      targeted folate-receptor over-expressed cancer cells while being simultaneously
      traced based on its inherent fluorescence. Intracellular localized NO and singlet
      oxygen were produced on demand by controlled visible light illumination,
      producing a synergistic cytotoxic effect to cancer cells. 

PMID- 25567667
TI  - Accelerated evolution of schistosome genes coding for proteins located at the
      host-parasite interface.
AB  - Study of proteins located at the host-parasite interface in schistosomes might
      provide clues about the mechanisms utilized by the parasite to escape the host
      immune system attack. Micro-exon gene (MEG) protein products and venom allergen
      like (VAL) proteins have been shown to be present in schistosome secretions or
      associated with glands, which led to the hypothesis that they are important
      components in the molecular interaction of the parasite with the host.
      Phylogenetic and structural analysis of genes and their transcripts in these two
      classes shows that recent species-specific expansion of gene number for these
      families occurred separately in three different species of schistosomes.
      Enrichment of transposable elements in MEG and VAL genes in Schistosoma mansoni
      provides a credible mechanism for preferential expansion of gene numbers for
      these families. Analysis of the ratio between synonymous and nonsynonymous
      substitution rates (dN/dS) in the comparison between schistosome orthologs for
      the two classes of genes reveals significantly higher values when compared with a
      set of a control genes coding for secreted proteins, and for proteins previously
      localized in the tegument. Additional analyses of paralog genes indicate that
      exposure of the protein to the definitive host immune system is a determining
      factor leading to the higher than usual dN/dS values in those genes. The
      observation that two genes encoding S. mansoni vaccine candidate proteins, known
      to be exposed at the parasite surface, also display similar evolutionary dynamics
      suggests a broad response of the parasite to evolutionary pressure imposed by the
      definitive host immune system.

PMID- 25567669
TI  - The effect of whole-body resonance vibration in a porcine model of spinal cord
      injury.
AB  - Whole-body vibration has been identified as a potential stressor to spinal cord
      injury (SCI) patients during pre-hospital transportation. However, the effect
      that such vibration has on the acutely injured spinal cord is largely unknown,
      particularly in the frequency domain of 5 Hz in which resonance of the spine
      occurs. The objective of the study was to investigate the consequences of
      resonance vibration on the injured spinal cord. Using our previously
      characterized porcine model of SCI, we subjected animals to resonance vibration
      (5.7+/-0.46 Hz) or no vibration for a period of 1.5 or 3.0 h. Locomotor function
      was assessed weekly and cerebrospinal fluid (CSF) samples were collected to
      assess different inflammatory and injury severity markers. Spinal cords were
      evaluated histologically to quantify preserved white and gray matter. No
      significant differences were found between groups for CSF levels of monocyte
      chemotactic protein-1, interleukin 6 (IL-6) and lL-8. Glial fibrillary acidic
      protein levels were lower in the resonance vibration group, compared with the non
      vibrated control group. Spared white matter tissue was increased within the
      vibrated group at 7 d post-injury but this difference was not apparent at the 12
      week time-point. No significant difference was observed in locomotor recovery
      following resonance vibration of the spine. Here, we demonstrate that exposure to
      resonance vibration for 1.5 or 3 h following SCI in our porcine model is not
      detrimental to the functional or histological outcomes. Our observation that a
      3.0-h period of vibration at resonance frequency induces modest histological
      improvement at one week post-injury warrants further study.

PMID- 25567670
TI  - Optimization of three-dimensional imaging on in vitro produced porcine
      blastocysts and chimeras for stem cell testing: a technology report.
AB  - Differential staining is an immunocytochemical staining that visualizes
      trophectoderm (TE) and the inner cell mass (ICM) of the blastocysts. It is used
      to determine the blastocyst quality, but could also be a useful tool to assess
      the integration site of injected cells into the early embryo. This is relevant
      for testing of presumed pluripotent stem cells. The gold standard for pluripotent
      stem cells is to test if the cells are capable of contributing to germline
      chimeras. Differential staining can be used to evaluate the possibility of
      chimeric contribution; if the cells are located in the area of the ICM they are
      likely to contribute to the fetus and if they are located in the area of the TE
      they are likely to contribute to the fetal membranes. In this article, we
      optimize on methods for embryo staining and mounting so that the exact location
      of injected stem cells within preimplantation porcine embryos can be evaluated. 

PMID- 25567672
TI  - Characteristics and help-seeking behaviors of Internet gamblers based on most
      problematic mode of gambling.
AB  - BACKGROUND: Previous studies of problem Internet gamblers have failed to
      distinguish whether their problem gambling relates to Internet or land-based
      gambling modes. Therefore, characteristics and help-seeking behaviors of people
      whose gambling problems relate specifically to Internet gambling are unknown, but
      could inform the optimal alignment of treatment and support services with the
      needs and preferences of problem gamblers. OBJECTIVE: This study aimed to compare
      (1) characteristics of problem Internet gamblers and problem land-based gamblers
      and (2) uptake of different types and modes of help between problem Internet
      gamblers and problem land-based gamblers. Hypothesis 1 was that problem Internet
      gamblers are less likely to seek help. Hypothesis 2 was that problem Internet
      gamblers are more likely to use online modes of help. METHODS: A sample of 620
      respondents meeting criteria for problem gambling was drawn from an online survey
      of 4594 Australian gamblers. Respondents were recruited through advertisements on
      gambling and gambling help websites, Facebook, and Google. Measures consisted of
      gambling participation; proportion of gambling on the Internet; most problematic
      mode of gambling; help seeking from 11 different sources of formal help, informal
      help, and self-help for gambling problems; psychological distress (Kessler 6);
      problem gambling severity (Problem Gambling Severity Index, PGSI); and
      demographics. RESULTS: Problem Internet gamblers were significantly more likely
      than problem land-based gamblers to be male (chi(2) 1=28.3, P<.001, phi=0.21),
      younger (t616.33=4.62, P<.001, d=0.37), have lower psychological distress (chi(2)
      1=5.4, P=.02, phi=0.09), and experience problems with sports and race wagering
      (chi(2) 4=228.5, P<.001, phi=0.61). Uptake of help was significantly lower among
      problem Internet compared to problem land-based gamblers (chi(2) 1=6.9, P<.001,
      phi=0.11), including from face-to-face services, gambling helplines, online
      groups, self-exclusion from land-based venues, family or friends, and self-help
      strategies. Both problem Internet and problem land-based gamblers had similarly
      low use of online help. However, problem land-based gamblers (37.6%, 126/335)
      were significantly more likely to have sought land-based formal help compared to
      problem Internet gamblers (23.5%, 67/285; chi(2) 1=14.3, P<.001, phi=0.15).
      CONCLUSIONS: The findings suggest that more targeted and innovative efforts may
      be needed to increase use of gambling help by problem Internet gamblers.
      Alternatively, their lower PGSI and K6 scores suggest Internet problem gamblers
      may have less need for gambling-related help. This is the first known study to
      classify problem Internet gamblers as those whose problem gambling specifically
      relates to Internet gambling. Further research is needed to better understand why
      help-seeking rates are lower among Internet problem gamblers.

PMID- 25567671
TI  - Approaches to passive mosquito surveillance in the EU.
AB  - The recent emergence in Europe of invasive mosquitoes and mosquito-borne disease
      associated with both invasive and native mosquito species has prompted
      intensified mosquito vector research in most European countries. Central to the
      efforts are mosquito monitoring and surveillance activities in order to assess
      the current species occurrence, distribution and, when possible, abundance, in
      order to permit the early detection of invasive species and the spread of
      competent vectors. As active mosquito collection, e.g. by trapping adults,
      dipping preimaginal developmental stages or ovitrapping, is usually cost-, time-
      and labour-intensive and can cover only small parts of a country, passive data
      collection approaches are gradually being integrated into monitoring programmes.
      Thus, scientists in several EU member states have recently initiated programmes
      for mosquito data collection and analysis that make use of sources other than
      targeted mosquito collection. While some of them extract mosquito distribution
      data from zoological databases established in other contexts, community-based
      approaches built upon the recognition, reporting, collection and submission of
      mosquito specimens by citizens are becoming more and more popular and
      increasingly support scientific research. Based on such reports and submissions,
      new populations, extended or new distribution areas and temporal activity
      patterns of invasive and native mosquito species were found. In all cases,
      extensive media work and communication with the participating individuals or
      groups was fundamental for success. The presented projects demonstrate that
      passive approaches are powerful tools to survey the mosquito fauna in order to
      supplement active mosquito surveillance strategies and render them more focused.
      Their ability to continuously produce biological data permits the early
      recognition of changes in the mosquito fauna that may have an impact on biting
      nuisance and the risk of pathogen transmission associated with mosquitoes.
      International coordination to explore synergies and increase efficiency of
      passive surveillance programmes across borders needs to be established. 

PMID- 25567673
TI  - Baseline characteristics and concerns of female cancer patients/survivors seeking
      treatment at a Female Sexual Medicine Program.
AB  - PURPOSE: The purpose of this study is to characterize patients seeking treatment
      at a Female Sexual Medicine and Women's Health Program and examine their
      sexual/vaginal health issues. METHODS: Data from clinical assessment forms were
      extracted from 509 women referred to the Female Sexual Medicine and Women's
      Health Program during/after cancer treatment. The form consists of a Vaginal
      Assessment Scale (VAS), vaginal health items, patient-reported outcomes (PROs)
      (Sexual Activity Questionnaire [SAQ], Sexual Self-Schema Scale [SSS], Female
      Sexual Function Index [FSFI]), and exploratory items. RESULTS: Of 509 patients,
      493 (97 %) completed PROs; 253 (50 %) received a pelvic examination. The majority
      had a history of breast (n = 260, 51 %), gynecologic (n = 184, 36 %), or
      colorectal/anal (n = 35, 7 %) cancer. Mean age was 51.2 years; 313 (62 %) were
      married/partnered. Approximately two thirds had elevated vaginal pH scores (5-6.5
      [35 %] or 6.5+ [33 %]) and minimal (62 %) or no (5 %) vaginal moisture. Eighty
      seven patients (44 %) experienced pain during their exam (23 % mild, 11 %
      moderate, 1.5 % severe, and 8.5 % not indicated). Fifty-three percent engaged in
      sexual activity with a partner; only 43 % felt confident about future sexual
      activity. Ninety-three percent were somewhat to very concerned/worried about
      sexual function/vaginal health. Approximately half had moderate/severe dryness (n
      = 133, 51 %) and dyspareunia (n = 120, 46 %). The mean SSS score was 60.7,
      indicating a slightly positive sexual self-view. However, 93.5 % (n = 429) had an
      FSFI score <26.55, suggesting sexual dysfunction. CONCLUSIONS: At initial
      consult, women reported vaginal dryness, pain, and sexual dysfunction. For many
      women, pelvic exams showed elevated vaginal pH, lack of moisture, and discomfort
      with the exam itself. Future analyses will examine changes over time.

PMID- 25567674
TI  - Synthesis of few-layer MoS2 nanosheet-loaded Ag3PO4 for enhanced photocatalytic
      activity.
AB  - Novel few-layer MoS2/Ag3PO4 composites were fabricated. The results indicated
      that Ag3PO4 nanoparticles were directly formed on the surface of few-layer MoS2.
      The physical and chemical properties of the few-layer MoS2/Ag3PO4 composite
      photocatalysts were tested in order to investigate the effects of few-layer MoS2
      on the photocatalytic activity of Ag3PO4. The photocatalytic activity of the few
      layer MoS2/Ag3PO4 composites was evaluated by the photocatalytic degradation of
      Rhodamine B (RhB) and bisphenol A (BPA) under visible light irradiation. The
      photocatalytic activity of the few-layer MoS2/Ag3PO4 composites was higher than
      that of pure Ag3PO4. The optimal few-layer MoS2 content for the organic pollutant
      degradation of the heterojunction structures was determined. The synergic effect
      between few-layer MoS2 and Ag3PO4 was found to lead to an improved photogenerated
      carrier separation. The stability and the possible photocatalytic mechanism of
      the composites were also discussed. 

PMID- 25567675
TI  - Tocochromanols composition in kernels recovered from different apricot varieties:
      RP-HPLC/FLD and RP-UPLC-ESI/MS(n) study.
AB  - Composition of tocochromanols in kernels recovered from 16 different apricot
      varieties (Prunus armeniaca L.) was studied. Three tocopherol (T) homologues,
      namely alpha, gamma and delta, were quantified in all tested samples by an RP
      HPLC/FLD method. The gamma-T was the main tocopherol homologue identified in
      apricot kernels and constituted approximately 93% of total detected tocopherols.
      The RP-UPLC-ESI/MS(n) method detected trace amounts of two tocotrienol homologues
      alpha and gamma in the apricot kernels. The concentration of individual
      tocopherol homologues in kernels of different apricots varieties, expressed in
      mg/100 g dwb, was in the following range: 1.38-4.41 (alpha-T), 42.48-73.27 (gamma
      T) and 0.77-2.09 (delta-T). Moreover, the ratio between individual tocopherol
      homologues alpha:gamma:delta was nearly constant in all varieties and amounted to
      approximately 2:39:1.

PMID- 25567676
TI  - A non-classical cannabinoid syndrome.
AB  - Hyperemesis cannabinoid syndrome (HCS) is characterized by cyclic vomiting and
      compulsive bathing behaviors in chronic cannabis users. This syndrome is not well
      known in the medical world and is underdiagnosed, despite the increasing use of
      cannabis. In this case report, physicians should keep in mind the criteria that
      characterize HCS syndrome. However, non-classical forms of HCS can exist with
      bradycardia, and pain can be relieved by cold temperature. 

PMID- 25567677
TI  - Development of a novel driving behavior adaptations questionnaire.
AB  - BACKGROUND: Driving a car requires adapting one's behavior to current task
      demands taking into account one's capacities. With increasing age, driving
      relevant cognitive performance may decrease, creating a need for risk-reducing
      behavioral adaptations. Three different kinds of behavioral adaptations are
      known: selection, optimization, and compensation. These can occur on the tactical
      and the strategic level. Risk-reducing behavioral adaptations should be
      considered when evaluating older drivers' traffic-related risks. METHODS: A
      questionnaire to assess driving-related behavioral adaptations in older drivers
      was created. The questionnaire was administered to 61 years older (age 65-87
      years; mean age = 70.2 years; SD = 5.5 years; 30 female, 31 male) and 31 younger
      participants (age 22-55 years; mean age = 30.5 years; SD = 6.3 years; 16 female
      and 15 male) to explore age and gender differences in behavioral adaptations.
      RESULTS: Two factors were extracted from the questionnaire, a risk-increasing
      factor and a risk-reducing factor. Group comparisons revealed significantly more
      risk-reducing behaviors in older participants (t(84.5) = 2.21, p = 0.013) and
      females (t(90) = 2.52, p = 0.014) compared, respectively, to younger participants
      and males. No differences for the risk-increasing factor were found (p > 0.05).
      CONCLUSIONS: The questionnaire seems to be a useful tool to assess driving
      related behavioral adaptations aimed at decreasing the risk while driving. The
      possibility to assess driving-related behavioral adaptations in a systematic way
      enables a more resource-oriented approach in the evaluation of fitness to drive
      in older drivers.

PMID- 25567678
TI  - Protective efficacy of individual CD8+ T cell specificities in chronic viral
      infection.
AB  - Specific CD8(+) T cells (CTLs) play an important role in resolving protracted
      infection with hepatitis B and C virus in humans and lymphocytic choriomeningitis
      virus (LCMV) in mice. The contribution of individual CTL specificities to chronic
      virus control, as well as epitope-specific patterns in timing and persistence of
      antiviral selection pressure, remain, however, incompletely defined. To monitor
      and characterize the antiviral efficacy of individual CTL specificities
      throughout the course of chronic infection, we coinoculated mice with a mixture
      of wild-type LCMV and genetically engineered CTL epitope-deficient mutant virus.
      A quantitative longitudinal assessment of viral competition revealed that mice
      continuously exerted CTL selection pressure on the persisting virus population.
      The timing of selection pressure characterized individual epitope specificities,
      and its magnitude varied considerably between individual mice. This longitudinal
      assessment of "antiviral efficacy" provides a novel parameter to characterize CTL
      responses in chronic viral infection. It demonstrates remarkable perseverance of
      all antiviral CTL specificities studied, thus raising hope for therapeutic
      vaccination in the treatment of persistent viral diseases. 

PMID- 25567679
TI  - A RIPK3-caspase 8 complex mediates atypical pro-IL-1beta processing.
AB  - Caspase 8, the initiator caspase for death receptor-induced apoptosis, functions
      as a negative regulator of receptor interacting protein kinase 3 (RIPK3), an
      essential factor for TNF-, TLR3-, and TLR4-induced necroptosis. In certain
      situations, caspase 8 can also participate in pro-IL-1beta processing. However,
      the biochemical complex that mediates caspase 8-mediated processing is not
      defined. In this study, we show that RIPK3 is crucial for caspase 1- and caspase
      8-mediated pro-IL-1beta and pro-IL-18 processing in bone marrow-derived dendritic
      cells (BMDCs) in response to LPS stimulation. Caspase 8-mediated pro-IL-1beta
      processing requires intact RIPK1, RIPK3, TRIF, and FADD. In response to LPS, a
      complex that contains RIPK1, RIPK3, FADD, and caspase 8 is formed. Surprisingly,
      RIPK3-specific kinase inhibitors strongly enhanced caspase 8 activation and pro
      IL-1beta processing in LPS-stimulated BMDCs. However, studies in BMDCs expressing
      the kinase-inactive RIPK3-K51A mutant or RIPK1-K45A mutant showed that the kinase
      activity of neither RIPK1 nor RIPK3 is required for LPS-induced caspase 8
      activation and IL-1beta secretion. Hence, RIPK3 is an unexpected positive
      regulator of caspase 8 activity that promotes IL-1beta maturation in BMDCs.

PMID- 25567680
TI  - TAM receptor-dependent regulation of SOCS3 and MAPKs contributes to
      proinflammatory cytokine downregulation following chronic NOD2 stimulation of
      human macrophages.
AB  - Microbial-induced cytokine regulation is critical to intestinal immune
      homeostasis. Acute stimulation of nucleotide-binding oligomerization domain 2
      (NOD2), the Crohn's disease-associated sensor of bacterial peptidoglycan, induces
      cytokines. However, cytokines are attenuated after chronic NOD2 and pattern
      recognition receptor stimulation of macrophages; similar attenuation is observed
      in intestinal macrophages. The role of Tyro3, Axl, and Mer (TAM) receptors in
      regulating chronic pattern recognition receptor stimulation and NOD2-induced
      outcomes has not been examined. Moreover, TAM receptors have been relatively less
      investigated in human macrophages. Whereas TAM receptors did not downregulate
      acute NOD2-induced cytokines in primary human macrophages, they were essential
      for downregulating signaling and proinflammatory cytokine secretion after chronic
      NOD2 and TLR4 stimulation. Axl and Mer were similarly required in mice for
      cytokine downregulation after chronic NOD2 stimulation in vivo and in intestinal
      tissues. Consistently, TAM expression was increased in human intestinal myeloid
      derived cells. Chronic NOD2 stimulation led to IL-10- and TGF-beta-dependent TAM
      upregulation in human macrophages, which, in turn, upregulated suppressor of
      cytokine signaling 3 expression. Restoring suppressor of cytokine signaling 3
      expression under TAM knockdown conditions restored chronic NOD2-mediated
      proinflammatory cytokine downregulation. In contrast to the upregulated
      proinflammatory cytokines, attenuated IL-10 secretion was maintained in TAM
      deficient macrophages upon chronic NOD2 stimulation. The level of MAPK activation
      in TAM-deficient macrophages after chronic NOD2 stimulation was insufficient to
      upregulate IL-10 secretion; however, full restoration of MAPK activation under
      these conditions restored c-Fos, c-Jun, musculoaponeurotic fibrosarcoma oncogene
      homolog K, and PU.1 binding to the IL-10 promoter and IL-10 secretion. Therefore,
      TAM receptors are critical for downregulating proinflammatory cytokines under the
      chronic NOD2 stimulation conditions observed in the intestinal environment. 

PMID- 25567681
TI  - Protease Inhibitors and Renal Function in Patients with HIV Infection: a
      Systematic Review.
AB  - INTRODUCTION: Despite antiretroviral (ARV) therapy reducing renal disease in
      human immunodeficiency virus overall, there is concern that certain ARVs,
      particularly tenofovir disoproxil fumarate (TDF) with or without a boosted
      protease inhibitor (PI), may reduce renal function over time. It is not known
      whether effects seen with PI-based regimens are independent, result from
      interactions with TDF coadministration, or are artefactual owing to inhibition of
      renal tubular creatinine transport by ritonavir or cobicistat
      pharmacoenhancement. The aim of this review was to conduct a systematic review of
      studies, weighted toward high-quality evidence, examining changes in renal
      function over time with PI-based regimens. METHODS: PubMed, Embase, and Medline
      databases and conference abstracts were searched using pre-defined terms for
      English language articles, published up to and including August 12, 2013,
      describing changes in renal function over time with PI-based regimens. All
      available randomized controlled trials (RCTs) were selected; however, to reduce
      bias, only observational studies recruiting from more than one center and
      analyzing data from more than 1,000 patients were included. Evidence was
      qualitatively evaluated according to levels established by the Oxford Centre for
      Evidence-Based Medicine (OCEBM). RESULTS: A total of 2,322 articles were
      retrieved by the initial search. Of these, 37 were selected for full review,
      comprising 24 RCTs (OCEBM Level 1 evidence: 4 reports of fully double-blinded or
      blinded with respect to the PI component). The remaining 20 RCTs and 13
      observational studies qualified as OCEBM Level 2 evidence. Level 1 evidence
      showed initial but non-progressive increases in serum creatinine and
      corresponding decreases in estimated glomerular filtration rate (eGFR),
      suggesting an effect on renal tubular transport of creatinine. Level 2 evidence
      suggested that atazanavir and lopinavir especially in combination with TDF were
      associated with non-progressive reductions in eGFR over time, with a decreased
      risk for the development of chronic kidney disease (CKD) on cessation and without
      the development of advanced CKD or end-stage renal disease (ESRD); whether these
      reductions were independent or associated with interactions with coadministered
      TDF could not be established with certainty. Data on darunavir were insufficient
      to draw any conclusions. The principal limitation of the reviewed studies was the
      lack of standardization of creatinine measurements in virtually all studies and
      the lack of corroborative data on changes in proteinuria or other indices of
      renal function. DISCUSSION: In this review, there was little evidence for
      progressive changes in eGFR, or the development of advanced CKD, or ESRD with
      lopinavir or atazanavir. Further long-term studies, employing a wide range of
      validated renal function assessments, are required to fully evaluate potential
      association of PIs with CKD.

PMID- 25567683
TI  - Acupuncture-induced pneumothorax: the hidden complication.
AB  - Acupuncture can be associated with potentially life-threatening complications.
      Although rare, we feel that potential complications are not being conveyed to
      patients. We present a case of acupuncture-induced pneumothorax and describe some
      changes to acupuncture practice that we would like to see implemented. 

PMID- 25567682
TI  - Effect of aerobic training and aerobic and resistance training on the
      inflammatory status of hypertensive older adults.
AB  - There is a relationship between high levels of inflammatory markers and low
      adhesion to the practice of physical activity in the older population. The
      objective of the present study was to compare the effect of two types of exercise
      programs, i.e., aerobic training and aerobic plus resistance training on the
      plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)
      of elderly hypertensive subjects. Hypertensive older volunteers in use of
      antihypertensive drugs were randomized to three groups: aerobic group (AG),
      resistance and aerobic group (RAG) and control group (CG). Training lasted 10
      weeks, with sessions held three times a week. Blood samples were collected before
      training and 24 h after completion of the 30 sessions for the determination of
      serum IL-6 and TNF-alpha levels. Body mass index was obtained before and after 10
      weeks. After intervention, BMI values were lower in AG and RAG compared to CG (p
      < 0.001), IL-6 was reduced in AG compared to CG (p = 0.04), and TNF-alpha levels
      were lower only in RAG compared to CG (p = 0.01). Concluding, both types of
      training were effective in reducing BMI values in hypertensive older subjects.
      Aerobic exercise produced the reduction of plasma IL-6 levels. However, the
      combination of aerobic and resistance exercise, which would be more indicated for
      the prevention of loss of functionality with aging, showed lower TNF-alpha
      mediator after training than control group and a greater fall of TNF-alpha levels
      associated to higher BMI reduction. 

PMID- 25567684
TI  - Polymer-mediated interactions and their effect on the coagulation-fragmentation
      of nano-colloids: a self-consistent field theory approach.
AB  - This feature paper reviews our recent efforts to theoretically model the effect
      of polymer mediated interactions on the coagulation-fragmentation of nano
      colloids in different settings encountered in practical systems. The polymer
      mediated interactions among nanoparticles play a key role in many biological and
      technological processes such as red blood cell aggregation, protein
      crystallization, self-healing of polymer composites, filler reinforcement of
      rubbers used in tire technology, etc. By developing and making use of the novel
      potential theory, we investigate several important cases of these interactions
      acting between nanoparticles in diverse nano-polymer composites. As a
      demonstration of its practical applicability, we use the developed theory to
      investigate the effect of polymer mediated interactions on the coagulation
      fragmentation of fillers and their kinetic stability in the presence of non
      adsorbing and adsorbing polymers. In particular, we use our findings to develop a
      pragmatic way of evaluating the kinetic stability of nano-filler agglomerates
      critical for understanding the filler reinforcement of rubbers. Finally, we
      perform thorough comparison of the present theoretical findings with the
      available experimental data and simulations. 

PMID- 25567685
TI  - Pediatric fatality review of the 2013 National Poison Database System (NPDS):
      focus on intent.

PMID- 25567686
TI  - The epidemiology and characteristics of carbon monoxide poisoning among
      recreational boaters.
AB  - INTRODUCTION: Carbon monoxide (CO) poisoning has been reported in the setting of
      recreational boating however, previous research addressing the epidemiology of
      carbon monoxide-related injury and death in recreational boaters has been
      limited. MATERIALS AND METHODS: The United States Coast Guard (USCG) Recreational
      Boating Statistics annual reports for the 10-year period 2002 - 2011 were
      analyzed to determine the epidemiology and characteristics of carbon monoxide
      poisoning among recreational boaters in the United States. Regression analysis
      was performed to determine statistical significance for trend. RESULTS: The mean
      number of accidents, injuries and deaths per year due to CO exposure on
      recreational watercrafts was 14.5 (95% CI 12.1-16.9), 30.9 (95% CI 22.4-39.4) and
      6.7 (95% CI 4.5-9.0) respectively. Cabin motorboats accounted for 49 accidents,
      123 injuries and 29 deaths. California had 24 carbon monoxide- related accidents
      over the 10-year study period. Regression analysis showed no overall linear trend
      in the number of carbon monoxide-related boating accidents, injuries, or deaths
      as an absolute number or as a percent of all boating accidents, injuries or
      deaths over the study period. Discussion. The majority of carbon monoxide-related
      boating accidents, injuries and deaths occurred with cabin motorboats. The state
      with the largest number of carbon monoxide-related accidents over the 10-year
      study period was California. CONCLUSIONS: Carbon monoxide-related accidents
      involving recreational boating constitute an important and under recognized cause
      of injury and death in the United States.

PMID- 25567689
TI  - Smoking habits, awareness of risks, and attitude towards tobacco control policies
      among medical students in Lagos, Nigeria.
AB  - BACKGROUND: This study aimed to assess the prevalence of cigarette smoking among
      medical students, and to determine their level of knowledge regarding risk
      associated with cigarette smoking and their attitude and behavior towards tobacco
      control strategies and policies. MATERIALS AND METHODS: A stratified random
      sampling approach was used to select participants. A modified version of the the
      Global Health Professional Students Survey questionnaire was self-administered.
      Descriptive statistics were applied and comparisons were done using chi-square
      test. Multivariate logistic regression was used to obtain the significant
      determinants of smoking. A P < 0.05 was considered significant. RESULTS: A total
      of 250 students participated in the study with a response rate of 89.2%. The mean
      age (years) was 21.4 +/- 3. Rate of ever smoking and current smoking was 9.6 and
      1.2%, respectively. Age > 21, having a smoking father, and use of alcohol were
      significantly associated with ever smoking. Knowledge of smoking as a risk for
      emphysema was 72.8%, coronary artery disease 82.8%, stroke 68.8%, and low birth
      weight 76.4%. There were 103 (41.2%) students aware of antidepressant usage in
      smoking cessation. One hundred and ninety-five (78%) offered smoking cessation
      advice if a smoker had no smoking-related disease and did not seek their opinion
      about smoking, 68.8% affirmed to having adequate knowledge on smoking cessation,
      and 56.8% had received formal training on smoking cessation techniques. The ban
      on cigarette smoking in enclosed public places was supported by 92.4%.
      CONCLUSIONS: The prevalence of current cigarette smoking among medical students
      in Lagos is relatively low. Gaps exist in the level of knowledge of the students
      regarding risks of cigarette smoking, tobacco cessation strategies, and in their
      attitude and behavior towards offering tobacco cessation advice. There is need
      therefore to include formal training on tobacco control strategies at an early
      stage in the medical curriculum.

PMID- 25567690
TI  - Prevalence of hypertension and its correlates among employees of a tertiary
      hospital in Yenagoa, Nigeria.
AB  - BACKGROUND: Hypertension (HTN) is a common medical problem with increasing
      prevalence and dire consequences. Considering the relative proximity of hospital
      workers to health care delivery, one may expect a better control of HTN and
      associated risk factors in this population. The objective of the current study
      was to determine the prevalence of HTN and risk factors among hospital employees
      in a Nigerian tertiary hospital. MATERIALS AND METHODS: All employees of the
      Federal Medical Center, Yenagoa (Bayelsa State, Nigeria) were invited for a HTN
      screening exercise on the world kidney day on March 14, 2013. A total of 231
      participants completed this cross-sectional study. Data was obtained with a pre
      tested interviewer-administered structured questionnaire while blood pressure was
      taken with an Accoson sphygmomanometer. Anthropometry was done using standardized
      protocols. Urine and blood were analyzed for glucose. HTN was defined as blood
      pressure >140/90 or prior diagnosis or use of antihypertensives. Data was
      entered, stored and analyzed with Statistical Package for Social Sciences (SPSS
      Inc., Chicago, IL, USA) version 20. RESULTS: The crude and age-adjusted
      prevalence of HTN among the hospital employee was 21.3% and 23.8% respectively.
      Age, marital status, educational level, body mass index, waist circumference (WC)
      and waist hip ratio showed significant association with HTN in the univariate
      analysis. However, in multivariate regression analysis, only older age and
      abnormal WC predicted HTN. CONCLUSION: The prevalence of HTN among the hospital
      employees compared with reports in other population and was predicted by
      advancing age and abnormal WC. The study underscores the need for introduction of
      HTN screening programs among hospital employees especially staff that are older
      with truncal obesity.

PMID- 25567691
TI  - Situational analysis of orphans and vulnerable children in urban and rural
      communities of Plateau State.
AB  - BACKGROUND: Orphans and Vulnerable Children (OVC) are children affected by HIV
      and AIDS by virtue of, among others, living in a household where one or more
      people are ill, dying or deceased, or which fosters orphans, and children whose
      care givers are too ill or old to continue to care for them. They often have more
      health needs than their peers. This study was carried out to obtain baseline
      information on the needs of OVC in North-Central Nigeria as a basis for provision
      of relief services. METHODS: A house to house cross-sectional survey of OVC
      recruited via a multistage sampling technique was carried out in four LGAs of
      Plateau State, Nigeria. The Child Status Index (CSI) tool was used to obtain
      information from the respondents and/or their caregivers. Vulnerability of the
      children was assessed using a Vulnerability Index (VI) scoring which ranged from
      1-21, with 1-9 being vulnerable, 10-14 more vulnerable, and 15-21 being most
      vulnerable. RESULTS: A total of 825 OVC ages ranging from 0-17 years and mean age
      of 9.8 +/- 4.5 years were studied. 432 were males (52.4%) and 393 females
      (47.6%). 64.8% lived in households headed by women out of which 77.6% were
      widows. Six hundred and one (72.8%) household heads were farmers. Paternal
      orphans made up 59.8% of the respondents and 12.1% had lost both parents.
      Prevalence of abuse/exploitation was 17.7% and 66.7% experienced household food
      insecurity. Four hundred and seventy-eight (57.9%) OVC lived in households with
      no source of income. One hundred and fifty-one (18.3%) children (54.9% boys and
      45.1% girls) had never been to school. 55.0% had minimal health problems.
      Majority of them (60.3%) lived in dilapidated shelter and 3.3% were living on the
      street. CONCLUSION: This survey revealed the various needs of OVC. Efforts to
      care, support and protect vulnerable children should not only focus on their
      immediate survival needs such as education, shelter and clothing, but also on
      long-term developmental needs that reduce children's vulnerability such as life
      skills, child protection, vocational training, food security and household
      economic strengthening.

PMID- 25567692
TI  - Iron deficiency anemia in an Egyptian pediatric population: a cross-sectional
      study.
AB  - OBJECTIVE: The aim of this study is to assess the frequency of iron deficiency
      anemia (IDA) and associated sociodemographic factors among children between 6
      months and 12 years of age. MATERIALS AND METHODS: This cross-sectional study
      enrolled 300 children from June 2011 to June 2012 visiting the pediatric
      outpatient clinics of Al-Fayoum University Hospital. Data were collected using a
      structured interview questionnaire. Sociodemographic variables studied included
      sex, residence, family size, fathers' education, mothers' education, and crowding
      index. Included patients were evaluated clinically and laboratory for complete
      blood picture, serum iron, serum ferritin, and transferrin saturation. RESULTS:
      It was found that 64% of studied children had IDA (20% mild, 41.7% moderate, and
      2.3% severe). The logistic regression analysis found that children from rural
      areas, those from low social class and those of low maternal educational level
      had a higher risk for IDA than other children. Infants with IDA were found to
      consume foods with low iron content 50% below recommended daily allowance.
      CONCLUSION: The high frequency of IDA is a severe public health problem in
      developing countries like Egypt, especially in children from rural areas, those
      from low social class and those of low maternal educational level. Iron-rich
      foods should be advised by health care providers. Prophylactic iron supplements
      should be given to all infants from 6 to 23 months.

PMID- 25567693
TI  - Microbiological assessment of well waters in Samaru, Zaria, Kaduna, State,
      Nigeria.
AB  - BACKGROUND: Majority of the human population in semi-urban and urban areas in
      Nigeria are heavily reliant on well water as the main source of water supply for
      drinking and domestic use due to inadequate provision of potable pipe borne
      water. These groundwater sources can easily be fecally contaminated and thus,
      increase the incidence and outbreaks of preventable waterborne diseases. This
      study was carried out to determine the bacteriological quality of some well
      waters in Samaru, Z. MATERIALS AND METHODS: Samaru, Zaria located in Northern
      Nigeria, is a semi-urban university satellite town blessed with abundant ground
      and surface water. Five sampling sites were randomly selected for this study. A
      total of 10 samples: Two from each of the sites were collected fortnightly for 1
      month (May-June, 2013). Samples were analyzed using presumptive multiple tube
      fermentation and confirmatory tests for total and fecal coliforms. The well water
      samples were also cultured for Salmonella, Shigella, and Vibrio chole. RESULTS:
      The total coliform count for all the samples analyzed was >180+/100 ml. All the
      well water samples from the study locations were contaminated with one or more
      bacterial pathogens, Escherichia coli 20%, Klebsiella pneumoniae 100% and Proteus
      mirabilis 40%. Salmonella, Shigella, or V. cholerae were not isolated from any of
      the well water samples. CONCLUSIONS: The results from this study showed
      contamination of all the wells studied with fecal coliforms thus, indicating the
      possible presence of other enteric pathogens and a potential source for
      waterborne disease outbreaks. Well water in Samaru is not safe for drinking
      without additional treatment like disinfection or boiling. Periodic testing and
      constant monitoring of well waters should also be done to meet up with the World
      Health Organization Standards in the provision of safe, clean drinking water .

PMID- 25567694
TI  - Blood pressure indices, life-style factors and anthropometric correlates of
      casual blood glucose in a rural Nigerian community.
AB  - BACKGROUND: Disordered blood glucose metabolism is associated with poor
      cardiovascular disease outcomes. Relationship between casual blood glucose (CBG)
      and blood pressure indices among rural dwellers in Nigeria has been less studied.
      METHODS: We measured CBG, anthropometry, systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) pulse pressure (PP) and mean arterial pressure
      (MAP) and life-style cardiovascular risk factors. RESULTS: The mean (standard
      deviation) of CBG was 6.2 (1.9) and values were similar in men and women. Age,
      SBP, DBP PP, MAP, body mass index (BMI) and waist circumference were positively
      correlated with CBG; r = 0.23, 0.30, 0.24, 0.28, 0.28, 0.24 and 0.22
      respectively. In a multivariate analysis, only PP and BMI predicted CBG. A 5 mmHg
      increase in PP or a 2 kg/m 2 increase in BMI increased CBG by 0.15 or 0.18 mmol
      respectively. PP and BMI in combination explained 13% of the variation in CBG (P
      < 0.001). CONCLUSION: PP and BMI are associated with CBG among rural dwellers in
      South-East Nigeria.

PMID- 25567695
TI  - Depression among adolescents attending secondary schools in South East Nigeria.
AB  - BACKGROUND: Depression among adolescents is an uncommon and frequently
      unrecognized issue in pediatrics. Children and adolescents however suffer from
      both depression and associated symptoms. METHODS: The study was carried out among
      adolescents in secondary schools from two states; Enugu and Ebonyi metropolises
      within the age range of 9-18 in Enugu metropolis. The instrument employed for
      data collection was a structured self-administered questionnaire developed from
      the Goldberg Depression Questionnaire, a Screening Test for Depression. It is
      particularly suited for students in this age group. The families were assigned
      socio-economic classes using the recommended method (modified) by Oyedeji.
      OBJECTIVES: The aims and objectives of this study were to determine the
      prevalence of several levels of depression among adolescents attending secondary
      schools in two states. RESULTS: A total of 453 adolescents who are attending
      secondary schools from two states were recruited in this study. Depression is non
      existent before the age of 10 years according to this study. The prevalence of
      moderate depression was lowest (2.3%) at the age of 10 and highest at (6.2%) the
      age of 13. The prevalence of severe depression was lowest (1.9%) at the age of 11
      and highest (7.4%) at the age of 12. Female gender is a risk factor for
      depression. Children whose parents are separated showed higher incidences of
      depression in all the spectra studied. CONCLUSION: Adolescents exhibit different
      levels of depression with a female preponderance.

PMID- 25567696
TI  - Transvaginal sonography is feasible and universally acceptable to women in
      Ibadan, Nigeria: experience from the 1st year of a novel service.
AB  - BACKGROUND: Transvaginal sonography (TVS) is the standard route for gynecological
      and early pregnancy assessment scanning, due to the higher resolution that
      allowed for a better view of the pelvis. It had not been available in the study
      area prior to this, and it was anticipated that clients would find it intrusive
      and unacceptable, and thus decline it. The study was aimed at accessing the
      acceptability of TVS in women. METHOD: A cross-sectional study of all clients who
      presented for gynecological and early pregnancy assessment scans at a private
      ultrasound diagnostic center in Nigeria during its 1st year of service. All
      suitable clients were counseled for TVS. This was carried out for them, while
      nonconsenters had transabdominal sonography. A questionnaire was administered to
      the consenting participants. Virgins and women currently experiencing heavy
      vaginal bleeding were excluded. Data were entered into SPSS-16 and analyzed with
      frequency tables. RESULTS: Five hundred and seventy-seven women of varied
      demographic characteristics were included into the study. Only one (i.e., 1/577;
      0.2%) declined TVS. The procedure was abandoned in one (i.e., 1/576; 0.2%) due to
      severe discomfort. All 575 that completed the examination stated they would
      accept TVS again in the future, if indicated. CONCLUSIONS: TVS was universally
      accepted by a diverse population of women in South-Western Nigeria. It is
      recommended that ultrasound scan providers in this location should acquire skills
      for it, if necessary, and that TVS be offered routinely for gynecological
      evaluation according to international standards.

PMID- 25567697
TI  - Is prostate-specific antigen a reliable marker for uterine leiomyoma detection?
AB  - BACKGROUND: Now it is accepted that prostate-specific antigen (PSA) is expressed
      extra prostatically and it is clear that many hormonally regulated female tissues
      show detectable PSA levels. This study was conducted due to differences of view
      between researchers about the role of PSA in some women diseases. This study was
      designed to evaluate the clinical implication of serum PSA measurement in
      diagnosis or management of patients with uterine myoma. MATERIALS AND METHODS:
      This was a case-control study. A total of 224 patients included in this study.
      Serum specimens were isolated and were stored at -70 degrees C until all
      specimens were completed. Wilcoxon's rank-sum test was used to identify
      statistically significant differences between the total PSA and free PSA
      measurements in patient groups. RESULTS: We noticed that there is no statistical
      significant correlation between total or free serum PSA level of cases with
      uterine myoma and control group (P = 0.433 and 0.700, respectively). Furthermore,
      no statistical difference was considered either in size or frequency of
      leiomyomas and free or total serum PSA (P = 0.126 and 0.433 and P = 0.997 and
      0.442, respectively). CONCLUSION: We concluded that serum PSA measurement has
      little clinical utility in diagnosis or management of uterine leiomyoma.

PMID- 25567698
TI  - Aspergillosis of the bone.
AB  - Aspergillosis of the long bones has not been reported. Those of the bones of the
      paranasal sinuses and ear canal have been reported but rare. A young woman
      reported to us with history of discharging sinuses around the right knee and
      recent fracture of the right femur. Despite all efforts, she ended up losing the
      whole limb from the hip. When a patient with Aspergillosis of the long bones
      presents late, amputation may be the best option. Early diagnosis will prevent
      this. 

PMID- 25567699
TI  - Acanthomatous ameloblastoma of mandible crossing the midline: a rare case report.
AB  - Ameloblastoma is the most common aggressive benign odontogenic tumor of the jaws.
      Ameloblastoma is a benign epithelial odontogenic tumor that typically arises in
      the mandible or maxilla or, rarely, in the immediate adjacent soft tissues. A
      clinical, radiographic and histopathological report is presented of a case of
      acanthomatous ameloblastoma in relation to molar in the left mandible of a 30
      year-old healthy male. The histopathological examination of the removed specimen
      revealed the histopathological pattern of an acanthomatous ameloblastoma. The
      radiographic appearance of the lesion showed the presence of multilocular
      radiolucencies, which were crossing the midline, which is rarely found in
      ameloblastoma. Due to its rarity and lack of data, we take this opportunity to
      present a world first case of acanthomatous ameloblastoma which was crossing the
      midline. 

PMID- 25567700
TI  - A novel approach for retreatment of multirooted tooth by partial radisection.
AB  - Modern advances in all phases of dentistry have provided the opportunity for
      patients to maintain a functional dentition for lifetime. Therapeutic measures
      performed to ensure retention of teeth vary in complexity. The treatment may
      involve combining restorative dentistry, endodontics, and periodontics so that
      the teeth are retained in whole or in part. Thus, tooth resection procedures are
      used to preserve as much tooth structure as possible rather than sacrificing the
      whole tooth. This treatment can produce predictable results as long as proper
      diagnostic, endodontic, surgical, prosthetic, and maintenance procedures are
      performed. The keys to long-term success appear to be thorough diagnosis,
      selection of patients with good oral hygiene and careful surgical and restorative
      management. 

PMID- 25567701
TI  - Surveillance for severe acute respiratory infections (SARI) in hospitals in the
      WHO European region - an exploratory analysis of risk factors for a severe
      outcome in influenza-positive SARI cases.
AB  - BACKGROUND: The 2009 H1N1 pandemic highlighted the need to routinely monitor
      severe influenza, which lead to the establishment of sentinel hospital-based
      surveillance of severe acute respiratory infections (SARI) in several countries
      in Europe. The objective of this study is to describe characteristics of SARI
      patients and to explore risk factors for a severe outcome in influenza-positive
      SARI patients. METHODS: Data on hospitalised patients meeting a syndromic SARI
      case definition between 2009 and 2012 from nine countries in Eastern Europe
      (Albania, Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Romania, Russian
      Federation and Ukraine) were included in this study. An exploratory analysis was
      performed to assess the association between risk factors and a severe (ICU,
      fatal) outcome in influenza-positive SARI patients using a multivariate logistic
      regression analysis. RESULTS: Nine countries reported a total of 13,275 SARI
      patients. The majority of SARI patients reported in these countries were young
      children. A total of 12,673 SARI cases (95%) were tested for influenza virus and
      3377 (27%) were laboratory confirmed. The majority of tested SARI cases were from
      Georgia, the Russian Federation and Ukraine and the least were from Kyrgyzstan.
      The proportion positive varied by country, season and age group, with a tendency
      to a higher proportion positive in the 15+ yrs age group in six of the countries.
      ICU admission and fatal outcome were most often recorded for influenza-positive
      SARI cases aged > 15 yrs. An exploratory analysis using pooled data from
      influenza-positive SARI cases in three countries showed that age > 15 yrs, having
      lung, heart, kidney or liver disease, and being pregnant were independently
      associated with a fatal outcome. CONCLUSIONS: Countries in Eastern Europe have
      been able to collect data through routine monitoring of severe influenza and
      results on risk factors for a severe outcome in influenza-positive SARI cases
      have identified several risk groups. This is especially relevant in the light of
      an overall low vaccination uptake and antiviral use in Eastern Europe, since
      information on risk factors will help in targeting and prioritising vulnerable
      populations.

PMID- 25567702
TI  - Implementation science in cancer prevention and control: a decade of grant
      funding by the National Cancer Institute and future directions.
AB  - BACKGROUND: The National Cancer Institute (NCI) has supported implementation
      science for over a decade. We explore the application of implementation science
      across the cancer control continuum, including prevention, screening, treatment,
      and survivorship. METHODS: We reviewed funding trends of implementation science
      grants funded by the NCI between 2000 and 2012. We assessed study characteristics
      including cancer topic, position on the T2-T4 translational continuum, intended
      use of frameworks, study design, settings, methods, and replication and cost
      considerations. RESULTS: We identified 67 NCI grant awards having an
      implementation science focus. R01 was the most common mechanism, and the total
      number of all awards increased from four in 2003 to 15 in 2012. Prevention grants
      were most frequent (49.3%) and cancer treatment least common (4.5%). Diffusion of
      Innovations and Reach, Effectiveness, Adoption, Implementation, Maintenance (RE
      AIM) were the most widely reported frameworks, but it is unclear how
      implementation science models informed planned study measures. Most grants (69%)
      included mixed methods, and half reported replication and cost considerations
      (49.3%). CONCLUSIONS: Implementation science in cancer research is active and
      diverse but could be enhanced by greater focus on measures development,
      assessment of how conceptual frameworks and their constructs lead to improved
      dissemination and implementation outcomes, and harmonization of measures that are
      valid, reliable, and practical across multiple settings.

PMID- 25567704
TI  - Supramolecular intracellular delivery of an anionic porphyrin by octaarginine
      conjugated per-O-methyl-beta-cyclodextrin.
AB  - A convenient and efficient method for intracellular delivery of a water-soluble
      anionic porphyrin has been developed by utilizing its supramolecular interaction
      with per-O-methyl-beta-cyclodextrin bearing an octaarginine chain as a cell
      penetrating peptide. 

PMID- 25567706
TI  - [Common expert-understandings of dental disease-control by combined prevention
      and treatment approach].

PMID- 25567703
TI  - Nausea and vomiting in early pregnancy and the risk of neural tube defects: a
      case-control study.
AB  - There has been considerable professional debate on the association between nausea
      and vomiting in early pregnancy (NVP) and neural tube defects (NTDs) risk. This
      study explored the association between NVP and NTDs risk, and the effect of folic
      acid supplements on the association. A 1:1 matched case-control study was
      conducted and conditional logistic regression model was used to analyze the
      associations. The result showed the odds ratio (OR) of severe NVP for NTDs was
      2.403 (95%CI 1.437,4.017; P<0.001) and that of moderate NVP was 1.469 (95%CI
      1.063,2.031; P = 0.020) compared with light NVP when adjusted by the potential
      confounders. Stratified by intake of folic acid supplements, the ORs for severe
      and moderate NVP turned to 2.147 (95%CI 1.140, 4.043; P = 0.018) and 2.055 (95%CI
      1.320, 3.199; P = 0.001) in the stratum of non-intake of folic acid supplements
      while ORs reduced to 1.851 (95%CI 0.729, 4.699; P = 0.195) and 1.003 (95%CI
      0.594, 1.694; P = 0.992) in the stratum of intake of folic acid supplements,
      respectively. We conclude that severe/moderate NVP has an association with the
      risk of NTDs, which was not found in the group with intake of folic acid
      supplements. Folic acid supplements should be recommended to use for the
      prevention of NTDs. 

PMID- 25567707
TI  - [The science of occlusion has its important academic position in stomatology].

PMID- 25567708
TI  - [Key points about temporomandibular disorders for dentists to understand in
      practice].

PMID- 25567709
TI  - [Application of quantitative sensory testing in oral and maxillofacial and body
      pain disorders].

PMID- 25567710
TI  - [Changes of periodontal Ruffini's corpuscle induced by experimental tooth
      movement in rats].
AB  - OBJECTIVE: To compare the ultra-microscopic changes of periodontal Ruffini's
      corpuscle induced by different patterns of tooth movement, and investigate the
      influence of different changes of the periodontal mechanical environment on the
      periodontal mechanoreceptor. METHODS: Thirty-two eight-weeks-old SD rats were
      divided into control group (n = 4), none-extraction group (n = 12) and extraction
      group (n = 12), and none-extraction group and extraction group were further
      divided into three subgroups, namely 3 day and 14 day and 28 day. For control
      group, no intervention was performed. For none-extraction group and extraction
      group, the following interventions were conducted. In none-extraction group, the
      maxillary left and mandibular right third molars were moved distally. In
      extraction group, the maxillary left third molar was moved distally, and the
      bilateral mandibular third molars were extracted. The ultra-structures of
      periodontal Ruffini's corpuscle in the periodontal ligament of the distal root of
      the bilateral maxillary third molars were observed under the transmission
      electron microscope. RESULTS: The ultra-structrural changes in the none
      extraction group were mainly characterized by degeneration or abnormal
      distribution of mitochondria in the axon terminal, which were almost recovered at
      28 d. In the extraction group, the changes were mainly characterized by
      deficiency or abnormal elongation of the Schwann sheath and were not recovered at
      28 d. CONCLUSIONS: The ultra-structures of periodontal Ruffini's corpuscle might
      be influenced by tooth movement and occlusal changes, and the mechanorecepting
      function of it might be affected by changes of the periodontal mechanical
      environment.

PMID- 25567711
TI  - [Characteristics of experimental occlusal interference-induced masticatory
      mechanical hyperalgesia of rats].
AB  - OBJECTIVE: To investigate the relationship between the existence of occlusal
      interference and masticatory muscle hyperalgesia by exploring the stimulus
      response relationship between the duration of occlusal interference and
      masticatory muscle mechanical withdrawal threshold. METHODS: Occlusal
      interference with 0.4 mm-thick crowns on rat molars was removed under anaesthesia
      at 2, 3, 4, 5, and 6 d after wear, and masticatory muscle mechanical withdrawal
      threshold was tested at 1, 3, 5, 7, 10, 14, 21 and 28 d. RESULTS: Decreased
      mechanical withdrawal thresholds were detected in temporal muscles and masseter
      muscles on both sides following occlusal interference (P < 0.05). After removal
      of crowns at 2, 3, 4 and 5 d, rats exhibited the similar head withdrawal
      thresholds as the sham-application control in masticatory muscles on both sides
      at 10, 14, 14 and 21 d (P > 0.05). No significant differences were detected
      between the contralateral side with the ipsilateral side (P < 0.05). After
      removal of crowns at 6 d, rats still exhibited significantly decreased head
      withdrawal thresholds[right temporal muscle: (1.365+/-0.018) N; right masseter:
      (1.437 +/- 0.024) N] in masticatory muscles on both sides until the last day of
      the experiment[the sham-application control: right temporal muscle: (1.554+/
      0.040) N, P < 0.001; right masseter: (1.546+/-0.019) N, P < 0.001]. CONCLUSIONS:
      The mechanical hyperalgesia can disappear after removal of the occlusal
      interference at 5 d, and the existence of the occlusal interference is positively
      correlated with the duration of the mechanical hyperalgesia.

PMID- 25567712
TI  - [Summary of colloquium of oral rehabilitation China 2013].

PMID- 25567713
TI  - [Effect of antibiotics on postoperative inflammatory complications after surgical
      extraction of the impacted mandibular third molar].
AB  - OBJECTIVE: To investigate the effect of antibiotics on postoperative inflammatory
      complications after surgical extraction of the impacted mandibular third molar.
      METHODS: Ninety-Six patients had their bilateral third molars removed through a
      split-mouth, double-blind, controlled, clinical trial in two visits. On one side
      amoxicillin (or clindamycin) was used (antibiotics group) from 1 h pre-operation
      to 3 d post-operation. On the other side, placebo was used (placebo group) the
      same time. Postoperative inflammatory complications including alveolar osteitis
      (AO), surgical site infection (SSI), pre-buccal site infection and anterior
      isthmus faucium space infection were monitored and recorded 2 d and 10 d after
      the surgery. The pain, swelling, and trismus were also recorded. RESULTS: All 96
      patients completed the study. Two AO (2.1%), one SSI (1.0%) and seven other
      infections were observed in the treatment group. Also three AO (3.1%), one SSI
      (1.0%) and eleven other infections were observed in the placebo group. However,
      no statistically significant differences were found in the incidence of various
      postoperative inflammatory complications and reactions between the groups (P >
      0.05). There was no significant difference on the postoperative reaction, except
      pain on 10 d. Patients who had inflammatory infection recovered well with
      symptomatic anti-infection treatment. CONCLUSIONS: The use of amoxicillin (or
      clindamycin) cannot effectively prevent and reduce the postoperative inflammatory
      complications after surgical extraction of the impacted mandibular third molar.

PMID- 25567714
TI  - [Comparison of the intraradicular bacterial community structures of teeth with or
      without post-treatment periapical periodontitis].
AB  - OBJECTIVE: To compare the intraradicular bacterial community structures of teeth
      with or without post-treatment periapical periodontitis and to explore the
      suspicious microorganisms that is related to persistent periapical infection.
      METHODS: The intraradicular biofilm samples were collected from 10 post-treatment
      periapical periodontitis teeth (apical periodontitis group) and 10 teeth without
      post-treatment periapical periodontitis (without apical periodontitis group). The
      V1-V3 hypervariable regions of bacterial 16S rRNA genes were amplified, and the
      high-throughput pyrosequencing was performed. The composition and structure
      characteristic of intraradicular microbiome were revealed by bioinformatic
      analysis. RESULTS: Total sequences were taxonomically classified into 132 species
      level bacteria belonging to 96 genera and 21 phyla. The most representive phyla
      in apical periodontitis group were Firmicutes [32% (18 534/58 688)],
      Proteobacteria [27% (15 626/58 688)], Actinobacteria [15% (8 685/58 688)],
      Bacteroidetes [11% (6163/58 688)], Fusobacteria [8% (4761/58688)] and
      Spirochaetes [3% (1 785/58 688)]. While the most representive phyla in without
      apical periodontitis group were Firmicutes [31% (16 941/55 480)], Proteobacteria
      [27% (14 748/55 480)], Bacteroidetes [18% (9 948/55 480)], Fusobacteria [10% (5
      307/55 480)], Actinobacteria [9% (4 761/55 480)], Chloroflexi [3% (1 785/55
      480)]. The abundance of actinobacteria in apical periodontitis group was
      significantly higher than without apical periodontitis group (P < 0.01). The
      detection rates of actinomycetes in apical periodontitis group and without apical
      periodontitis group were 100% and 50%. CONCLUSIONS: The diversity of
      intraradicular bacterial community in teeth with apical periodontitis was higher
      than those without apical periodontitis. Actinomycetes may be related to post
      treatment periapical periodontitis.

PMID- 25567715
TI  - [Ephrin B2 is involved in Porphyromonas gingivalis infection-enhanced adhesion of
      THP-1 to human umbilical vein endothelial cells].
AB  - OBJECTIVE: To investigate the mechanisms of Porphyromonas gingivalis (Pg)
      infection-mediated enhancement of adhesion between monocytes THP-1 and human
      umbilical vein endothelial cells (HUVEC) by detecting the effect of
      erythropoietin producing hepatomocellular receptor interacting protein B2 (Ephrin
      B2) and its receptors on the adhesion. METHODS: PgATCC33277 was cultured in an
      anaerobic jar, and THP-1 cells were infected with various concentrations of Pg at
      multiplicity of infection (MOI) of 1:100 for 8 and 24 h, respectively. The
      expression of Ephrin B2 receptor of THP-1 cells was detected. After removal of
      the free Pg, THP-1 cells were cocultured with HUVEC (overexpress of EphrinB2 or
      not) for 24 h to detect the expression of Ephrin B2 of HUVEC cells after
      additional cultivation for 23 h. RESULTS: The adhesion of THP-1 cells post
      infection by Pg to HUVEC was enhanced. The mRNA levels of Ephrin B2 receptors,
      including EphB3 (5.169+/-0.152, P = 0.005), EphB4 (11.040+/-1.195, P = 0.001),
      and EphA4 (4.976+/- 0.122, P = 0.001) expressed by THP-1, and Ephrin B2 (8.938+/
      0.962, P = 0.008) expressed by HUVEC were significantly elevated 24 h post
      infection of Pg. Over expression of Ephrin B2 in HUVEC promoted the adhesion of
      THP-1 to HUVEC. CONCLUSIONS: Ephrin B2 and its receptors are involved in Pg
      infection mediated enhancement of the adhesion of THP-1 to HUVEC cells,
      suggesting that Ephrin B2 participates in the development of atherosclerosis.

PMID- 25567716
TI  - [Effect of estrogen deficiency on the proliferation and osteogenic
      differentiation potential of mandibular bone marrow stromal cells].
AB  - OBJECTIVE: To determine the effects of estrogen deficiency on the proliferation
      and osteogenic differentiation of mandibular bone marrow stromal cells (mBMSC).
      METHODS: Ten 8-week-old female SD rats were randomly divided into two groups,
      ovariectomized group (OVX, n = 5) and sham-operation group (n = 5). All rats were
      anesthetized and both ovaries of OVX-rats were gently removed. Sham-operation
      rats were treated with the same incisions to expose the ovaries but without any
      hurt to them. One month after the operation, the mandibular bones were gently
      separated and mBMSC were isolated. Methyl thiazolyl tetrazolium (MTT) assay,
      alkaline phosphotase (ALP) activity, alizarin red staining, real-time reverse
      transcription (RT)-PCR and Western blotting were respectively used to examine the
      proliferative activity and osteogenic potential of mBMSC. RESULTS: MTT results
      showed that OVX-mBMSC exhibited the decreased proliferative activity as compared
      with Sham-mBMSC. ALP activity of OVX-mBMSC [(0.710+/-0.011) Sigma unit/protein]
      was lower than that of Sham-mBMSC [(1.512+/-0.021) Sigma unit/protein] (P <
      0.01). Alizarin red staining showed that OVX-mBMSC formed less calcified nodules
      than Sham-mBMSC. Ca(2+) concentration analysis showed Ca(2+) of OVX-mBMSC
      [(0.433+/-0.045) ug/g] was less than Sham-mBMSC [(1.453+/-0.131) ug/g] (P <
      0.01). Real-time RT-PCR and Western blotting results showed that the expression
      of osteogenic markers (Alp, Runx2/RUNX2, Osx/OSX, Ocn/OCN) in OVX-mBMSC was
      significantly inhibited as compared with Sham-mBMSC (P < 0.05). CONCLUSIONS:
      Estrogen deficiency significantly inhibits the proliferation and osteogenic
      capacity of mBMSC.

PMID- 25567717
TI  - [Design and fabrication of the custom-made titanium condyle by selective laser
      melting technology].
AB  - OBJECTIVE: To design and fabricate the custom-made titanium mandibular condyle by
      the reverse engineering technology combined with selective laser melting (SLM)
      technology and to explore the mechanical properties of the SLM-processed samples
      and the application of the custom-made condyle in the temporomandibular joint
      (TMJ) reconstruction. METHODS: The three-dimensional model of the mandibular
      condyle was obtained from a series of CT databases. The custom-made condyle model
      was designed by the reverse engineering software. The mandibular condyle was made
      of titanium powder with a particle size of 20-65 um as the basic material and the
      processing was carried out in an argon atmosphere by the SLM machine. The yield
      strength, ultimate strength, bending strength, hardness, surface morphology and
      roughness were tested and analyzed. The finite element analysis (FEA) was used to
      analyze the stress distribution. RESULTS: The complex geometry and the surface of
      the custom-made condyle can be reproduced precisely by the SLM. The mechanical
      results showed that the yield strength, ultimate strength, bending strength and
      hardness were (559+/-14) MPa, (659+/-32) MPa, (1 067+/-42) MPa, and (212+/-4)HV,
      respectively. The surface roughness was reduced by sandblast treatment.
      CONCLUSIONS: The custom-made titanium condyle can be fabricated by SLM technology
      which is time-saving and highly digitized. The mechanical properties of the SLM
      sample can meet the requirements of surgical implant material in the clinic. The
      possibility of fabricating custom-made titanium mandibular condyle combined with
      the FEA opens new interesting perspectives for TMJ reconstruction.

PMID- 25567718
TI  - [Perioperative medication for oral surgery].

PMID- 25567719
TI  - [The role of gingival epithelium defence in the occurrence of periodontitis].

PMID- 25567720
TI  - [Discussions on the madality of surgery for papillary cystadenoma lympho
      matosum].

PMID- 25567721
TI  - Structure and bonding in amorphous iron carbide thin films.
AB  - We investigate the amorphous structure, chemical bonding, and electrical
      properties of magnetron sputtered Fe(1-xCx) (0.21 ? x ? 0.72) thin films. X-ray,
      electron diffraction and transmission electron microscopy show that the Fe(1-xCx)
      films are amorphous nanocomposites, consisting of a two-phase domain structure
      with Fe-rich carbidic FeC(y), and a carbon-rich matrix. Pair distribution
      function analysis indicates a close-range order similar to those of crystalline
      Fe(3)C carbides in all films with additional graphene-like structures at high
      carbon content (71.8 at% C). From x-ray photoelectron spectroscopy measurements,
      we find that the amorphous carbidic phase has a composition of 15-25 at% carbon
      that slightly increases with total carbon content. X-ray absorption spectra
      exhibit an increasing number of unoccupied 3d states and a decreasing number of C
      2p states as a function of carbon content. These changes signify a systematic
      redistribution in orbital occupation due to charge-transfer effects at the domain
      size-dependent carbide/matrix interfaces. The four-point probe resistivity of the
      Fe(1-xCx) films increases exponentially with carbon content from ~200 MUOmega cm
      (x = 0.21) to ~1200 MUOmega cm (x = 0.72), and is found to depend on the total
      carbon content rather than the composition of the carbide. Our findings open new
      possibilities for modifying the resistivity of amorphous thin film coatings based
      on transition metal carbides through the control of amorphous domain structures.

PMID- 25567722
TI  - Synthesis, in vitro and in vivo antitumor and antiviral activity of novel 1
      substituted benzimidazole derivatives.
AB  - A novel series of 5-nitro-1H-benzimidazole derivatives substituted at position 1
      by heterocyclic rings was synthesized. Cytotoxicity and antiviral activity of the
      new compounds were tested. Compound 3 was more active than doxorubicin against A
      549, HCT-116 and MCF-7. However, compound 3 showed no activity against human
      liver carcinoma Hep G-2 cell line. Compounds 9 and 17b (E) showed potency near to
      doxorubicin against the four cell lines. The acute toxicity of compound 9 on
      liver cancer induced in rats was determined in vivo. Interestingly, it showed
      restoration activity of liver function and pathology towards normal as compared
      to the cancer-bearing rats induced by DENA. Compounds 17a (Z), 17b (E) and 18a
      (Z) were the most promising compounds for their antiviral activity against
      rotavirus Wa strain. 

PMID- 25567723
TI  - Suspension-Expansion of Bone Marrow Results in Small Mesenchymal Stem Cells
      Exhibiting Increased Transpulmonary Passage Following Intravenous Administration.
AB  - Mesenchymal stem cells (MSCs) have been extensively explored in a variety of
      regenerative medicine applications. The relatively large size of MSCs expanded in
      tissue culture flasks leads to retention in the microcirculation of the lungs
      following intravenous delivery, reducing their capacity to reach target sites. We
      explored whether the expansion of whole marrow in suspension cultures would yield
      smaller MSCs with increased capacity to traverse the pulmonary microcirculation
      compared with traditional monolayer cultures. We tested this hypothesis using rat
      marrow in a suspension bioreactor culture with fibronectin-coated microcarriers,
      leading to sustained expansion of both the microbead-adherent cells, as well as
      of a nonadherent cell fraction. Magnetic depletion of CD45(+) cells from the
      bioreactor cultures after 5 weeks led to a highly enriched
      CD73(+)/CD90(+)/CD105(+) MSC population. The bioreactor-grown MSCs were
      significantly smaller than parallel monolayer MSCs (15.1 +/- 0.9 MUm vs. 18.5 +/-
      2.3 MUm diameter, p<0.05). When fluorescently labeled bioreactor-grown MSCs were
      intravenously injected into rats, the peak cell concentration in the arterial
      circulation was an order of magnitude higher than similarly delivered monolayer
      grown MSCs (94.8 +/- 29.6 vs. 8.2 +/- 5.6/10(6) nucleated blood cells,
      respectively, p<0.05). At 24 h after intravenous injection of the LacZ-labeled
      bioreactor-grown MSCs, there was a significant threefold decrease in the LacZ
      labeled MSCs trapped in the lungs, with a significant increase in the cells
      reaching the spleen and liver in comparison to their monolayer MSC counterparts.
      Bioreactor-grown whole marrow cell cultures yielded smaller MSCs with increased
      capacity to traverse the pulmonary microcirculation compared with traditionally
      expanded monolayer MSCs. This may significantly improve the capacity and
      efficiency of these cells to home to injury sites downstream of the lungs.

PMID- 25567725
TI  - This month in Evolutionary Applications.

PMID- 25567724
TI  - Hysteresis in the surfactant-induced volume transition of hydrogels.
AB  - The discontinuous uptake and release of surfactants by hydrogels and the
      accompanying discontinuous volume transition is known to occur with a hysteresis.
      We have performed a theoretical analysis in order to find the mechanistic origin
      of this phenomenon. Using a mean-field model, we have quantitatively reproduced
      the experimental behavior by considering the cost of elastically deforming the
      gel material to allow phase coexistence. The major part of the hysteresis is due
      to the high phase coexistence cost of the swelling transition, since in this
      direction the coexistence cost depends not only on the elasticity of the network
      (being a weak force in comparison) but also on the entropy of the monovalent
      nonsurfactant electrolyte present in the system. 

PMID- 25567728
TI  - Estimation of effective number of breeders from molecular coancestry of single
      cohort sample.
AB  - The effective population size, N e, is an important parameter in population
      genetics and conservation biology. It is, however, difficult to directly estimate
      N e from demographic data in many wild species. Alternatively, the use of genetic
      data has received much attention in recent years. In the present study, I propose
      a new method for estimating the effective number of breeders N eb from a
      parameter of allele sharing (molecular coancestry) among sampled progeny. The
      bias and confidence interval of the new estimator are compared with those from a
      published method, i.e. the heterozygote-excess method, using computer simulation.
      Two population models are simulated; the noninbred population that consists of
      noninbred and nonrelated parents and the inbred population that is composed of
      inbred and related parents. Both methods give essentially unbiased estimates of N
      eb when applied to the noninbred population. In the inbred population, the
      proposed method gives a downward biased estimate, but the confidence interval is
      remarkably narrowed compared with that in the noninbred population. Estimate from
      the heterozygote-excess method is nearly unbiased in the inbred population, but
      suffers from a larger confidence interval. By combining the estimates from the
      two methods as a harmonic mean, the reliability is remarkably improved. 

PMID- 25567726
TI  - Evolutionary origins of invasive populations.
AB  - What factors shape the evolution of invasive populations? Recent theoretical and
      empirical studies suggest that an evolutionary history of disturbance might be an
      important factor. This perspective presents hypotheses regarding the impact of
      disturbance on the evolution of invasive populations, based on a synthesis of the
      existing literature. Disturbance might select for life-history traits that are
      favorable for colonizing novel habitats, such as rapid population growth and
      persistence. Theoretical results suggest that disturbance in the form of
      fluctuating environments might select for organismal flexibility, or
      alternatively, the evolution of evolvability. Rapidly fluctuating environments
      might favor organismal flexibility, such as broad tolerance or plasticity.
      Alternatively, longer fluctuations or environmental stress might lead to the
      evolution of evolvability by acting on features of the mutation matrix. Once
      genetic variance is generated via mutations, temporally fluctuating selection
      across generations might promote the accumulation and maintenance of genetic
      variation. Deeper insights into how disturbance in native habitats affects
      evolutionary and physiological responses of populations would give us greater
      capacity to predict the populations that are most likely to tolerate or adapt to
      novel environments during habitat invasions. Moreover, we would gain fundamental
      insights into the evolutionary origins of invasive populations. 

PMID- 25567727
TI  - Turner syndrome and the evolution of human sexual dimorphism.
AB  - Turner syndrome is caused by loss of all or part of an X chromosome in females. A
      series of recent studies has characterized phenotypic differences between Turner
      females retaining the intact maternally inherited versus paternally inherited X
      chromosome, which have been interpreted as evidence for effects of X-linked
      imprinted genes. In this study I demonstrate that the differences between Turner
      females with a maternal X and a paternal X broadly parallel the differences
      between males and normal females for a large suite of traits, including lipid
      profile and visceral fat, response to growth hormone, sensorineural hearing loss,
      congenital heart and kidney malformations, neuroanatomy (sizes of the cerebellum,
      hippocampus, caudate nuclei and superior temporal gyrus), and aspects of
      cognition. This pattern indicates that diverse aspects of human sex differences
      are mediated in part by X-linked genes, via genomic imprinting of such genes,
      higher rates of mosaicism in Turner females with an intact X chromosome of
      paternal origin, karyotypic differences between Turner females with a maternal
      versus paternal X chromosome, or some combination of these phenomena. Determining
      the relative contributions of genomic imprinting, karyotype and mosaicism to
      variation in Turner syndrome phenotypes has important implications for both
      clinical treatment of individuals with this syndrome, and hypotheses for the
      evolution and development of human sexual dimorphism. 

PMID- 25567729
TI  - Modeling genetic connectivity in sticklebacks as a guideline for river
      restoration.
AB  - Estimating genetic connectivity in disturbed riverine landscapes is of key
      importance for river restoration. However, few species of the disturbed riverine
      fauna may provide a detailed and basin-wide picture of the human impact on the
      population genetics of riverine organisms. Here we used the most abundant native
      fish, the three-spined stickleback (Gasterosteus aculeatus L.), to detect the
      geographical determinants of genetic connectivity in the eastern part of the
      Scheldt basin in Belgium. Anthropogenic structures came out as the strongest
      determinant of population structure, when evaluated against a geographically well
      documented baseline model accounting for natural effects. These barriers not only
      affected genetic diversity, but they also controlled the balance between gene
      flow and genetic drift, and therefore may crucially disrupt the population
      structure of sticklebacks. Landscape models explained a high percentage of
      variation (allelic richness: adjusted R (2) = 0.78; pairwise F ST: adjusted R (2)
      = 0.60), and likely apply to other species as well. River restoration and
      conservation genetics may highly benefit from riverine landscape genetics,
      including model building, the detection of outlier populations, and a specific
      test for the geographical factors controlling the balance between gene flow and
      genetic drift. 

PMID- 25567730
TI  - Asymmetrical local adaptation of maize landraces along an altitudinal gradient.
AB  - Crop landraces are managed populations that evolve in response to gene flow and
      selection. Cross-pollination among fields, seed sharing by farmers, and selection
      by management and environmental conditions play roles in shaping crop
      characteristics. We used common gardens to explore the local adaptation of maize
      (Zea mays ssp. mays) landrace populations from Chiapas, Mexico to altitude. We
      sowed seeds of 21 populations from three altitudinal ranges in two common gardens
      and measured two characteristics that estimate fitness: likelihood of producing
      good quality seed and the total mass of good quality seed per plant. The
      probability of lowland plants producing good quality seed was invariably high
      regardless of garden, while highland landraces were especially sensitive to
      altitude. Their likelihood of producing good seed quadrupled in the highland
      site. The mass of good quality seed showed a different pattern, with lowland
      landraces producing 25% less seed mass than the other types at high elevations.
      Combining these two measures of fitness revealed that the highland landraces were
      clearly adapted to highland sites, while lowland and midland landraces appear
      more adapted to the midland site. We discuss this asymmetry in local adaptation
      in light of climate change and in situ conservation of crop genetic resources. 

PMID- 25567731
TI  - Mixed evidence for reduced local adaptation in wild salmon resulting from
      interbreeding with escaped farmed salmon: complexities in hybrid fitness.
AB  - Interbreeding between artificially-selected and wild organisms can have negative
      fitness consequences for the latter. In the Northwest Atlantic, farmed Atlantic
      salmon recurrently escape into the wild and enter rivers where small, declining
      populations of wild salmon breed. Most farmed salmon in the region derive from an
      ancestral source population that occupies a nonacidified river (pH 6.0-6.5). Yet
      many wild populations with which escaped farmed salmon might interbreed inhabit
      acidified rivers (pH 4.6-5.2). Using common garden experimentation, and examining
      two early-life history stages across two generations of interbreeding, we showed
      that wild salmon populations inhabiting acidified rivers had higher survival at
      acidified pH than farmed salmon or F1 farmed-wild hybrids. In contrast, however,
      there was limited evidence for reduced performance in backcrosses, and F2 farmed
      wild hybrids performed better or equally well to wild salmon. Wild salmon also
      survived or grew better at nonacidified than acidified pH, and wild and farmed
      salmon survived equally well at nonacidified pH. Thus, for acid tolerance and the
      stages examined, we found some evidence both for and against the theory that
      repeated farmed-wild interbreeding may reduce adaptive genetic variation in the
      wild and thereby negatively affect the persistence of depleted wild populations. 

PMID- 25567732
TI  - Clinal patterns of desiccation and starvation resistance in ancestral and
      invading populations of Drosophila subobscura.
AB  - As invading species expand, they eventually encounter physical and biotic
      stressors that limit their spread. We examine latitudinal and climatic variation
      in physiological tolerance in one native and two invading populations of
      Drosophila subobscura. These flies are native to the Palearctic region, but
      invaded both South and North America around 1980 and spread rapidly across 15
      degrees  of latitude on each continent. Invading flies rapidly evolved
      latitudinal clines in chromosome inversion frequencies and in wing size that
      parallel those of native populations in the Old World. Here we investigate
      whether flies on all three continents have evolved parallel clines in desiccation
      and starvation tolerance, such that flies in low-latitude regions (hot, dry)
      might have increased stress resistance. Starvation tolerance does not vary with
      latitude or climate on any continent. In contrast, desiccation tolerance varies
      clinally with latitude on all three continents, although not in parallel. In
      North American and Europe, desiccation tolerance is inversely related to
      latitude, as expected. But in South America, desiccation tolerance increases with
      latitude and is greatest in relatively cool and wet areas. Differences among
      continents in latitudinal patterns of interspecific-competition potentially
      influence clinal selection for physiological resistance, but no simple pattern is
      evident on these continents. 

PMID- 25567733
TI  - Small-scale biocomplexity in coastal Atlantic cod supporting a Darwinian
      perspective on fisheries management.
AB  - Harvesting of marine resources raises concerns about how to identify and preserve
      biocomplexity, including the diversity of life histories found within and among
      wild populations of a species. In order to fully accomplish this, there is a need
      to elucidate the underlying causes of phenotypic variation, and how this
      variation responds to environmental changes. In general, both evolutionary
      (genetic) and nonevolutionary (plastic) responses may occur. Plastic responses to
      environmental change are expected to shift the phenotype along a reaction norm,
      while an evolutionary response is expected to shift the reaction norm itself.
      Here, we assess the maturation patterns of coastal Atlantic cod (Gadus morhua) in
      Skagerrak, where studies using neutral markers have revealed genetically
      differentiated populations of this harvested fish within tens of kilometres of
      coastline. Our results suggest that physiological state prior to the spawning
      season, as well as juvenile growth, both influence the probability of completing
      sexual maturation at a given age. Furthermore, our results point towards a
      spatial structuring of this plasticity (i.e. the maturation reaction norms)
      comparable with population connectivity inferred from neutral markers. We argue
      that such fine-scale biocomplexity calls for a Darwinian approach to fisheries
      management. 

PMID- 25567734
TI  - Long-term behavior of groundwater chemistry in a periodically rewetted fen area
      covered with macrophytes.
AB  - We studied the long-term changes in groundwater composition in the context of
      peat restoration at a degraded water-table managed peatland site typical for many
      agriculturally used fen areas in the northern hemisphere. At the study site,
      peatland rewetting with groundwater control and pumped canal water was carried
      out in two periods: from 1997 to 2002 and from 2011 to 2013. The site was not
      managed between 2002 and 2011, which led to an unstable groundwater table that
      had declined in part. The aim of this study was to investigate the consequences
      of rewetting and desiccation on groundwater chemistry. We pursued a multivariate
      approach using nonlinear principal component analysis (Isomap) to identify the
      prevailing processes that control the groundwater quality in this system. Sixteen
      years after peatland restoration, the groundwater quality had significantly
      improved. Principal component analysis revealed that hydrological processes had a
      major impact on groundwater quality, i.e. fluctuations between upwelling of
      local, salt-influenced groundwater and downwelling of surface and rainwater
      (first principal component) as well as upwelling of regional groundwater from
      deeper layers (second principal component) which originated from the catchment.
      In particular, the upwelling of regional deep groundwater had a strong positive
      impact on the groundwater quality of upper layers at the Biesenbrow site. Another
      major impact on groundwater quality was nutrient withdrawal by macrophytes and
      incorporation into organic matter. In the upper groundwater layer, peat
      mineralization processes resulted in substantially increased SO4 concentrations.
      We concluded that potential matter release after rewetting is buffered by
      hydrological barriers, and seems to be marginal with little impact on adjacent
      environments in the long term. The ecosystem is sustainably stabilized, and
      therefore has no negative impact on groundwater quality during periods of water
      shortage. Due to the strong influence of regional groundwater, management
      measures in the catchment are very important for maintaining and improving
      groundwater quality in peatlands. 

PMID- 25567735
TI  - Can zero-valent iron nanoparticles remove waterborne estrogens?
AB  - Steroidal estrogens are one of the most challenging classes of hazardous
      contaminants as they can cause adverse effects to biota in extremely low
      concentrations. They emerge in both waste waters and surface waters serving as a
      source of drinking water. Environmental Quality Standards for 17beta-estradiol
      (E2) and 17alpha-ethinylestradiol (EE2), promulgated within the EU Water
      Framework Directive, are 0.4 and 0.035 ng L(-1), respectively. Because nanoscale
      zero-valent iron (nZVI) particles have been previously used in numerous
      remediation technologies and have the advantage of possible magnetic separation,
      interaction of nZVI with E2 and EE2 in water was investigated to assess the
      potential role of nZVI in removing steroidal estrogens. A mixture of E2 and EE2
      dissolved in water was shaken with varying doses of nZVI for 1-5 h. Concentration
      dependent removal of the estrogens was observed but removal did not increase
      significantly with time. Concentrations of the estrogens were determined by
      HPLC/MS/MS and a biodetection reporter gene assay. Sorption and nonspecific
      oxygen-mediated oxidation of estrogens were identified as the most probable
      removal mechanisms. Two independent experiments confirmed that significant
      decrease of estrogens concentration is achieved when at least 2 g L(-1) of nZVI
      is applied. The presented study provides insights into the mechanisms of nZVI
      interaction with steroidal estrogens under aerobic conditions prevailing in
      currently applied water treatment technologies.

PMID- 25567736
TI  - Fragmented local governance and water resource management outcomes.
AB  - Fragmented jurisdictions and decision making structures can result in destructive
      competition and/or a lack of systematic cooperation that can hamper effective
      resource management and environmental planning, although the value of local
      autonomy and stakeholder participations should not be underestimated. This study
      empirically examines if political fragmentation in local governance is a
      significant barrier to successful resource management. To test this hypothesis,
      the authors quantify the degree of political fragmentation at two different
      geographical scales - 1) site-level: 12-digit watersheds and 2) regional:
      metropolitan statistical areas or equivalent regions - and analyze how water
      resource management outcomes vary with the level of political fragmentation using
      nationwide land cover and stream gauge information in the U.S. Regression
      analysis shows water quality declines (or slower quality improvements), measured
      in terms of total suspended solids, are associated with both site-level and
      regional political fragmentation indicators, suggesting that political
      fragmentation can make resource management more challenging. 

PMID- 25567737
TI  - The effects of study order and backward associative strength on illusory
      recollection: A source-strength effect does not always occur.
AB  - We investigated illusory recollection by dividing lists of associated words into
      three subsets (high, medium and low) based on their backward associative strength
      (BAS) to an unstudied theme. Participants studied these subsets at different
      visual locations on a computer screen and afterwards were given a source memory
      test. In Experiment 1, we varied the order in which high- and medium-BAS subsets
      were studied. In Experiment 2, we again manipulated study order as well as the
      associative strength of the medium-BAS subsets (strong or weak). Across both
      experiments, illusory recollection was constrained by both study order and BAS.
      Source attributions to the high-BAS location were more likely (a source-strength
      effect) when high-BAS items were studied first or studied following items of
      relatively low associative strength. However, attributions to the strong medium
      BAS studied location were more likely when these items were studied before high
      BAS items. These findings are interpreted as resulting from misbinding of source
      details at encoding which can be explained by the activation-monitoring theory of
      illusory recollection. 

PMID- 25567738
TI  - Comparison of primary radial head replacement and ORIF (open reduction and
      internal fixation) in Mason type III fractures: a retrospective evaluation in 72
      elderly patients.
AB  - BACKGROUND: The aim of this study was to compare radial head prosthesis
      replacement with open reduction and internal fixation (ORIF) in the surgical
      treatment of Mason type III radial head fractures in 72 elderly patients.
      MATERIAL/METHODS: Seventy-two elderly patients (mean age, 67.1+/-1.25 years,
      range, 62-81 years) with Mason type III radial head fractures were treated from
      January 2001 to June 2012. Of these, 37 cases received radial prosthesis and 35
      cases were treated with ORIF. All patients were followed up for 10 to 15.6
      months. RESULTS: Based on the elbow functional evaluation criteria score by
      Broberg and Morrey, 29 cases achieved excellent results, 7 were good, and 1 was
      fair in the replacement group. In the ORIF group, excellent results were seen in
      24 cases, good in 9, and fair in 2. The rates of good or excellent results were
      78.4% and 68.6% for prosthesis replacement patients and ORIF patients,
      respectively (P<0.05). The Visual Analogue Scores (VAS) for replacement and ORIF
      groups were 2.25 and 1.67, respectively (P<0.05). CONCLUSIONS: The radial head
      prosthesis replacement method is a relatively better surgical approach than ORIF
      in the treatment of elderly patients with Mason type III radial head fractures.

PMID- 25567739
TI  - Acute treatment-resistant post-partum necrotising myopathy with anti-Ro52/TRIM21
      antibodies treated with rituximab.

PMID- 25567740
TI  - Absence of salivary CCL28 in primary Sjogren's syndrome.
AB  - CCL28 is a mucosa-associated epithelial-cell-produced chemokine involved in oral
      defense. We assessed the level of CCL28 in saliva of primary Sjogren's syndrome
      (pSS) patients in comparison with healthy controls and correlated it with IgA
      salivary levels. We included 30 non-smoker pSS patients and 30 non-smoker healthy
      controls paired by age (+/-5 years). Saliva samples were collected during the
      morning and kept frozen at -86  degrees C until the analysis. Fifty microliters
      of saliva was diluted 3:1 with water and analyzed for CCL28 salivary levels by
      ELISA method. The samples were tested in triplicate. IgA salivary levels were
      tested by ELISA method. We used descriptive statistics, Mann-Whitney U test and
      Kendall's tau correlation coefficients. pSS patients were mostly females (93.3
      %), mean age 54.5 +/- 13.3 years and median disease duration of 7.6 years (0.5
      33). Patients with pSS had lower levels of salivary CCL28 when compared with
      controls [0 (0-1,272 pg/ml) vs. 94.4 (0-5,810) pg/ml, p < 0.0001]. pSS patients
      also had lower median levels of salivary IgA [72.55 MUg/ml (0.40-297.4)] than
      controls [131.9 MUg/ml (6.8-281.8)], although the latter results did not reach
      statistical significance (p = 0.51). Among the SS group, there was no correlation
      between CCL28 and IgA salivary levels nor between salivary IgA and disease
      duration, salivary flow, serum immunoglobulins or dental loss. CCL28 was absent
      in saliva of pSS patients; however, this finding did not correlate with salivary
      IgA levels. 

PMID- 25567741
TI  - Emergence of photoautotrophic minimal protocell-like supramolecular assemblies,
      "Jeewanu" synthesied photo chemically in an irradiated sterilised aqueous mixture
      of some inorganic and organic substances.
AB  - Sunlight exposed sterilised aqueous mixture of ammonium molybdate, diammonium
      hydrogen phosphate, biological minerals and formaldehyde showed photochemical
      formation of self-sustaining biomimetic protocell-like supramolecular assemblies
      "Jeewanu" (Bahadur and Ranganayaki J Brit Interplanet Soc 23:813-829 1970). The
      structural and functional characteristics of Jeewanu suggests that in possible
      prebiotic atmosphere photosy nergistic collaboration of non-linear processes at
      mesoscopic level established autocatalytic pathways on mineral surfaces by
      selforganisation and self recognition and led to emergence of similar earliest
      energy transducing supramolecular assemblies which might have given rise to
      common universal ancestor on the earth or elsewhere. 

PMID- 25567743
TI  - Field electron emission enhancement of graphenated MWCNTs emitters following
      their decoration with Au nanoparticles by a pulsed laser ablation process.
AB  - A plasma-enhanced chemical vapor deposition (PECVD) process was adapted to alter
      the growth of multiwall carbon nanotubes (MWCNTs) so that graphene sheets grow
      out of their tips. Gold nanoparticle (Au-NP) decoration of graphenated MWCNTs (g
      MWCNTs) was obtained by subsequent decoration by a pulsed laser deposition (PLD)
      process. By varying the number of laser ablation pulses (N(Lp)) in the PLD
      process, we were able to control the size of the gold nanoparticles and the
      surface coverage of the decorated g-MWCNTs. The presence of Au-NPs,
      preferentially located at the tip of the g-MWCNTs emitters, is shown to
      significantly improve the field electron emission (FEE) properties of the global
      g-MWCNT/Au-NP nanohybrid films. Indeed, the electric field needed to extract a
      current density of 0.1 MUA cm(-)(2) from the g-MWCNT/Au-NP films was decreased
      from 2.68 V MUm(-1) to a value as low as 0.96 V MUm(-1). On the other hand, UV
      photoelectron spectroscopy (UPS) characterization revealed a decrease in the
      global work function of the Au-decorated g-MWCNT nanohybrids compared to that of
      bare g-MWCNT emitters. Surprisingly, the work function of g-MWCNT was found to
      decrease from 4.9 to 4.7 eV with the addition of Au-NPs-a value lower than the
      work function of both materials worth 5.2 and 4.9 eV for gold and g-MWCNT,
      respectively. Our results show that the N(Lp) dependence of the FEE
      characteristics of the g-MWCNT/Au-NP emitters correlates well with their work
      function changes. Fowler-Nordheim-theory-based calculations suggest that the
      significant FEE enhancement of the emitters is also caused by the Au-NPs acting
      as nanoscale electric field enhancers.

PMID- 25567742
TI  - Cyclic guanosine monophosphate does not inhibit gonadotropin-induced activation
      of mitogen-activated protein kinase 3/1 in pig cumulus-oocyte complexes.
AB  - BACKGROUND: Recent results indicate a key role for cyclic guanosine monophosphate
      (cGMP) in the regulation of oocyte meiotic arrest in preovulatory mammalian
      follicles. The aim of our study was to determine whether the resumption of oocyte
      meiosis and expansion of cumulus cells in isolated pig cumulus-oocyte complexes
      (COCs) can be blocked by a high intracellular concentration of cGMP, and whether
      this effect is mediated by a cGMP-dependent inhibition of mitogen-activated
      protein kinase 3/1 (MAPK3/1). METHODS: The COCs were isolated from ovaries of
      slaughtered gilts and cultured in vitro in M199 supplemented with 5% fetal calf
      serum. The expression levels of the C-type natriuretic peptide (CNP) precursor
      (NPPC) and its receptor (NPR2) mRNAs during the culture of COCs were determined
      by real-time RT-PCR. To control the intracellular concentration of cGMP in the
      COCs, the culture medium was further supplemented with CNP or various
      concentrations of synthetic cGMP analogues; the concentration of cGMP in COCs was
      then assessed by ELISA. The effect of the drugs on oocyte maturation was assessed
      after 24 and 44 h of culture by determining nuclear maturation. The expansion of
      cumulus cells was assessed by light microscopy and the expression of cumulus
      expansion-related genes by real-time RT-PCR. A possible effect of cGMP on FSH
      induced activation of MAPK3/1 was assessed by immunoblotting the COC proteins
      with phospho-specific and total anti-Erk1/2 antibodies. RESULTS: The COCs
      expressed NPPC and NPR2, the key components of cGMP synthesis, and produced a
      large amount of cGMP upon stimulation with exogenous CNP, which lead to a
      significant (P < 0.05) delay in oocyte meiotic resumption. The COCs also
      responded to cGMP analogues by inhibiting the resumption of oocyte meiosis. The
      inhibitory effect of cGMP on meiotic resumption was reversed by stimulating the
      COCs with FSH. However, high concentration of intracellular cGMP was not able to
      suppress FSH-induced activation of MAPK3/1 in cumulus cells, cumulus expansion
      and expression of expansion-related genes (P > 0.05). CONCLUSIONS: The findings
      of this study indicate that high cGMP concentrations inhibit the maturation of
      pig oocytes in vitro but the inhibitory mechanism does not involve the
      suppression of MAPK3/1 activation in cumulus cells.

PMID- 25567744
TI  - Erythropoietin enhances whole body lipid oxidation during prolonged exercise in
      humans.
AB  - Animal studies have suggested that erythropoietin, besides its well-known
      hematopoietic effects, can modulate metabolism and prevent fat accumulation. We
      investigated the effects of repeated injections of recombinant human
      erythropoietin (EPO) on the balance of substrate oxidation during aerobic
      exercise in humans. Twelve healthy aerobically trained males received
      subcutaneously either moderate dose of EPO (50 U/kg, EPO) or saline injections
      (NaCl 0.9 %, control) three times a week for 4 weeks. Body weight, % fat, maximal
      aerobic capacity, and substrate utilization during exercise were assessed before
      and after treatment, while hemoglobin and hematocrit were monitored regularly
      during the treatment. Carbohydrate and fat oxidation were evaluated via indirect
      calorimetry, during a submaximal exercise performed at 75 % of the participants'
      maximal aerobic capacity (V(O2max)) for 60 min. Results showed that 4 weeks of
      EPO treatment significantly enhanced fat oxidation (+56 % in EPO versus -9 % in
      control) during exercise, independent of its effects on hematological parameters
      or V(O2max). This study shows that EPO can modulate substrate utilization during
      exercise, leading to enhanced fat utilization and lower use of carbohydrates.
      This opens new research directions exploring whether systemic EPO levels, in
      physiological conditions, participate to the modulation of fat oxidation.

PMID- 25567745
TI  - Deregulation of NF-kB-miR-146a negative feedback loop may be involved in the
      pathogenesis of diabetic neuropathy.
AB  - The current study was designed to explore whether microRNA-146a and its adapter
      proteins (tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and
      interleukin-1 receptor-associated kinase 1 (IRAK1)) are involved in the
      pathogenesis of diabetes neuropathy. Twelve male Sprague Dawley rats were
      randomized into control and diabetic groups (n = 6). Diabetes was induced by a
      single-dose injection of nicotinamide (110 mg/kg; i.p.), 15 min before injection
      of streptozotocin (50 mg/kg; i.p.) in 12-h-fasted rats. Diabetic neuropathy was
      evaluated by hot plate and tail emersion tests, 2 months after the injection of
      streptozotocin. The gene expression level of microRNA-146a (miR-146a), IRAK1,
      TRAF6, and nuclear factor kappa B (NF-kappaB) was measured in the sciatic nerve
      of rats using the real time-PCR method. Moreover, the activity of NF-kappaB and
      the concentration of pro-inflammatory cytokines were determined by the ELISA
      method. In comparison with the control group, a threefold increase in the
      expression of miR-146a and NF-kappaB, and a twofold decrease in the expression of
      TRAF6 were observed in the sciatic nerve of diabetic rats. Furthermore, the NF
      kappaB activity and the concentration of TNF-alpha, interleukin 6 (IL-6), and
      interleukin 1beta (IL-1beta) in the sciatic nerve of diabetic rats were higher
      than in those of control counterparts. These results suggest that a defect in the
      NF-kB-miR-146a negative feedback loop may be involved in the pathogenesis of
      diabetic neuropathy.

PMID- 25567746
TI  - Characterization of the amino acid residues mediating the unique amino-sugar-1
      phosphate acetyltransferase activity of the archaeal ST0452 protein.
AB  - The ST0452 protein from the thermophilic archaean Sulfolobus tokodaii has been
      identified as an enzyme with multiple sugar-1-phosphate nucleotidylyltransferase
      and amino-sugar-1-phosphate acetyltransferase (amino-sugar-1-P AcTase)
      activities. Analysis of the protein showed that in addition to glucosamine-1
      phosphate (GlcN-1-P) AcTase activity, it possesses unique galactosamine-1
      phosphate (GalN-1-P) AcTase activity not detected in any other proteins.
      Comparison of the crystal structures of the ST0452 protein and GlmU from
      Escherichia coli (EcGlmU), which possesses only GlcN-1-P AcTase activity, showed
      that the overall sequence identity between these two proteins is less than 25 %,
      but the amino acid residues predicted to comprise the catalytic center of EcGlmU
      are conserved in the ST0452 protein. To understand the molecular mechanism by
      which the ST0452 amino-sugar-1-P AcTase activity recognizes two independent
      substrates, several ST0452 substitution and truncation mutant proteins were
      constructed and analyzed. We found that His308 is essential for both GalN-1-P and
      GlcN-1-P AcTase activities, whereas Tyr311 and Asn331 are important only for the
      GalN-1-P AcTase activity. In addition, deletion of the C-terminal 5 or 11
      residues showed that the 11-residue C-terminal region exerts a modest stimulatory
      effect on GalN-1-P AcTase activity but dramatically suppresses GlcN-1-P AcTase
      activity. This region also appears to make an important contribution to the
      thermostability of the entire ST0452 protein. Systematic deletions from the C
      terminus also demonstrated that the C-terminal region with the beta-helix
      structure has an important role mediating the trimerization of the ST0452
      protein. This is the first report of an analysis of a thermostable archaeal
      enzyme exhibiting multiple amino-sugar-1-P AcTase activities.

PMID- 25567747
TI  - Prevalence of coronary atherosclerosis in an Asian population: findings from
      coronary computed tomographic angiography.
AB  - We sought to estimate the prevalence of coronary atherosclerosis by coronary
      computed tomographic angiography (CCTA) and to identify risk factors attributable
      to the development of coronary atherosclerosis in an asymptomatic Asian
      population. We analyzed 6,311 consecutive asymptomatic individuals aged 40 and
      older with no prior history of coronary artery disease (CAD) who voluntarily
      underwent CCTA evaluation as part of a general health examination. The mean age
      of study participants was 54.7 +/- 7.4 years, and 4,594 (72.8%) were male. After
      age and gender adjustment using the population census of the National Statistical
      Office, the prevalence of plaque was 40.5% [95% confidence interval (CI) 38.1
      42.9], and significant CAD (diameter stenosis >=50%) was observed in 9.0% (95% CI
      7.7-10.2). Individuals with significant CAD were significantly older than those
      without (59.2 +/- 8.8 vs. 54.0 +/- 7.1 years, p < 0.001). Compared with
      individuals with no cardiovascular risk factors, there was a higher prevalence of
      significant CAD in individuals with diabetes mellitus [standardized rate ratio
      (SRR) 2.66; 95% CI 1.93-3.68; p < 0.001], hypertension (SRR 2.24; 95% CI 1.69
      2.97; p < 0.001), or hyperlipidemia (SRR 1.65; 95% CI 1.25-2.17; p < 0.001).
      There was also a greater prevalence of significant CAD in individuals with an
      intermediate or high Framingham risk score (SRR 5.91; 95% CI 2.34-14.95; p <
      0.001) or a high atherosclerotic cardiovascular disease risk score (SRR 8.04; 95%
      CI 3.04-21.23; p < 0.001). The prevalence of coronary atherosclerosis in this
      Asian population was not negligible and was associated with known cardiovascular
      risk factors and high-risk individuals.

PMID- 25567749
TI  - Erratum to: CXCL1 promotes arteriogenesis through enhanced monocyte recruitment
      into the peri-collateral space.

PMID- 25567748
TI  - Novel HSAN1 mutation in serine palmitoyltransferase resides at a putative
      phosphorylation site that is involved in regulating substrate specificity.
AB  - 1-Deoxysphingolipids (1-deoxySL) are atypical sphingolipids that are formed by
      the enzyme serine palmitoyltransferase (SPT) due to a promiscuous use of L
      alanine over its canonical substrate L-serine. Several mutations in SPT are
      associated with the hereditary sensory and autonomic neuropathy type I (HSAN1).
      The current hypothesis is that these mutations induce a permanent shift in the
      affinity from L-serine toward L-alanine which results in a pathologically
      increased 1-deoxySL formation in HSAN1 patients. Also, wild-type SPT forms 1
      deoxySL under certain conditions, and elevated levels were found in individuals
      with the metabolic syndrome and diabetes. However, the molecular mechanisms which
      control the substrate shift of the wild-type enzyme are not understood. Here, we
      report a novel SPTLC2-S384F variant in two unrelated HSAN1 families. Affected
      patients showed elevated plasma 1-deoxySL levels and expression of the S384F
      mutant in HEK293 cells increased 1-deoxySL formation. Previously, S384 has been
      reported as one of the two (S384 and Y387) putative phosphorylation sites in
      SPTLC2. The phosphorylation of wild-type SPTLC2 was confirmed by isoelectric
      focusing. The impact of an S384 phosphorylation on SPT activity was tested by
      creating mutants mimicking either a constitutively phosphorylated (S384D, S384E)
      or non-phosphorylated (S384A, Y387F, Y387F+S384A) protein. The S384D but not the
      S384E variant was associated with increased 1-deoxySL formation. The other
      mutations had no influence on activity and substrate affinity. In summary, our
      data show that S384F is a novel mutation in HSAN1 and that the substrate
      specificity of wild-type SPT might by dynamically regulated by a phosphorylation
      at this position. 

PMID- 25567750
TI  - Diagnosis of human preimplantation embryo viability.
AB  - BACKGROUND: Transfer of more than a single embryo in an IVF cycle comes with the
      finite possibility of a multiple gestation. Even a twin pregnancy confers
      significant risk to both mother and babies. The move to single-embryo transfer
      for all patients will be greatly facilitated by the ability to quantify embryo
      viability. Developments in time-lapse incubation systems have provided new
      insights into the developmental kinetics of the human preimplantation embryo.
      Advances in molecular methods of chromosomal analysis have created platforms for
      highly effective screening of biopsied embryos, while noninvasive analysis of
      embryo physiology reveals more about the embryo than can be determined by
      morphology alone. METHODS: Recent developments in time-lapse microscopy,
      molecular karyotyping and in proteomics and metabolomics have been assessed and
      presented here in a descriptive review. RESULTS AND CONCLUSIONS: New algorithms
      are being created for embryo selection based on their developmental kinetics in
      culture, and the impact of factors such as patient etiology and treatment are
      being clarified. Potential links between morphokinetic data and embryo karyotype
      are being elucidated. The introduction of new molecular methods of determining
      embryo chromosomal complement is proving to be accurate and reproducible, with
      the future trending toward CGH arrays or next generation sequencing as a rapid
      and reliable means of analysis, that should be suitable for each IVF clinic to
      adopt. A relationship between embryo metabolism and viability is established and
      is now being considered together with morphokinetic data to create more robust
      algorithms for embryo selection. Microfluidic devices have the capacity and
      potential to be used in human IVF clinics for the routine diagnosis of embryo
      biomarkers.

PMID- 25567751
TI  - Inhibition of induced nitric oxide synthase enhances the anti-tumor effects on
      cancer immunotherapy using TLR7 agonist in mice.
AB  - Toll-like receptor (TLR) agonists have been shown to have anti-tumor activity in
      basic research and clinical studies. However, TLR agonist monotherapy in cancer
      treatment dose not sufficiently eliminate tumors. Activation of the innate immune
      response by TLR agonists and other pathogen-associated molecular patterns is
      effective for driving adaptive immunity via interleukin (IL)-12 or IL-1, but is
      counteracted by the simultaneous induction of immunosuppressive cytokines and
      other molecules, including IL-10, tumor growth factor-beta, and induced nitric
      oxide synthase (iNOS). In the present study, we evaluated the anticancer effect
      of the TLR7 agonist, imiquimod (IMQ), in the absence of iNOS. The administration
      of IMQ in iNOS-knockout (KO) mice implanted with tumor cells significantly
      suppressed tumor progression as compared to that in wild-type mice and improved
      the survival rate. Moreover, injection with IMQ enhanced the tumor antigen
      specific Th1 response in iNOS-KO mice with tumors. The enhancement of the antigen
      specific Th1 response was associated with an increase in IL-2 and IL-12b
      expressions in the tumor-draining lymph nodes. Combination therapy with IMQ and
      an iNOS inhibitor also significantly inhibited tumor growth in the established
      tumor model. Finally, our results indicated that the enhancement of iNOS
      expression through the administration with TLR agonists impairs host anti-tumor
      immunity, while the inhibition of iNOS could enhance the therapeutic efficacy of
      TLR agonists via the increase in Th1 immune response.

PMID- 25567752
TI  - Enhanced multiple vibrational resonances by Na+ and K+ dynamics in a neuron
      model.
AB  - Some neuronal receptors perceive external input in the form of hybrid periodic
      signals. The signal detection may be based on the mechanism of vibrational
      resonance, in which a system's response to the low frequency signal can become
      optimal by an appropriate choice of the vibration amplitude of HFS. The
      vibrational resonance effect is investigated in a neuron model in which the intra
      and extra-cellular potassium and sodium concentrations are allowed to evolve
      temporally, depending on ion currents, Na(+)-K(+) pumps, glial buffering, and ion
      diffusion. Our results reveal that, compared to the vibrational resonances in the
      model with constant ion concentrations, the significantly enhanced vibrational
      multi-resonances can be observed for the single neuron system where the potassium
      and sodium ion concentrations vary temporally. Thus, in contradiction to a
      popular view that ion concentrations dynamics play little role in signal
      detection, we indicate that the neuron's response to an external subthreshold
      signal can be largely improved by sodium and potassium dynamics. 

PMID- 25567753
TI  - A high-resolution computational model of the deforming human heart.
AB  - Modeling of the heart ventricles is one of the most challenging tasks in soft
      tissue mechanics because cardiac tissue is a strongly anisotropic incompressible
      material with an active component of stress. In most current approaches with
      active force, the number of degrees of freedom (DOF) is limited by the direct
      method of solution of linear systems of equations. We develop a new approach for
      high-resolution heart models with large numbers of DOF by: (1) developing a hex
      dominant finite element mixed formulation and (2) developing a Krylov subspace
      iterative method that is able to solve the system of linearized equations for
      saddle-point problems with active stress. In our approach, passive cardiac tissue
      is modeled as a hyperelastic, incompressible material with orthotropic
      properties, and mixed pressure-displacement finite elements are used to enforce
      incompressibility. Active stress is generated by a model with force dependence on
      length and velocity of muscle shortening. The ventricles are coupled to a lumped
      circulatory model. For efficient solution of linear systems, we use Flexible
      GMRES with a nonlinear preconditioner based on block matrix decomposition
      involving the Schur complement. Three methods for approximating the inverse of
      the Schur complement are evaluated: inverse of the pressure mass matrix; least
      squares commutators; and sparse approximate inverse. The sub-matrix corresponding
      to the displacement variables is preconditioned by a V-cycle of hybrid geometric
      algebraic multigrid followed by correction with several iterations of GMRES
      preconditioned by sparse approximate inverse. The overall solver is demonstrated
      on a high-resolution two ventricle mesh based on a human anatomy with roughly 130
      K elements and 1.7 M displacement DOF. Effectiveness of the numerical method for
      active contraction is shown. To the best of our knowledge, this solver is the
      first to efficiently model ventricular contraction using an iterative linear
      solver for the mesh size demonstrated and therefore opens the possibility for
      future very high-resolution models. In addition, several relatively simple
      benchmark problems are designed for a verification exercise to show that the
      solver is functioning properly and correctly solves the underlying mathematical
      model. Here, the output of the newly designed solver is compared to that of the
      mechanics component of Chaste ('Cancer, Heart and Soft Tissue Environment').
      These benchmark tests may be used by other researchers to verify their newly
      developed methods and codes. 

PMID- 25567754
TI  - Simulation of short-term pressure regulation during the tilt test in a coupled 3D
      0D closed-loop model of the circulation.
AB  - Short-term fluctuations in arterial pressures arising from normal physiological
      function are buffered by a negative feedback system known as the arterial
      baroreflex. Initiated by altered biomechanical stretch in the vessel wall, the
      baroreflex coordinates a systemic response that alters heart rate, cardiac
      contractility and peripheral vessel vasoconstriction. In this work, a coupled 3D
      0D formulation for the short-term pressure regulation of the systemic circulation
      is presented. Including the baroreflex feedback mechanisms, a patient-specific
      model of the large arteries is subjected to a simulated head up tilt test.
      Comparative simulations with and without baroreflex control highlight the
      critical role that the baroreflex has in regulating variations in pressures
      within the systemic circulation. 

PMID- 25567756
TI  - Capsule commentary on Vyas et al., Diet drink consumption and the risk of
      cardiovascular events: a report from the Women's Health Initiative.

PMID- 25567755
TI  - Trends in the ambulatory management of headache: analysis of NAMCS and NHAMCS
      data 1999-2010.
AB  - BACKGROUND: Headache is a frequent complaint and among the most common reasons
      for visiting a physician. OBJECTIVE: To characterize trends from 1999 through
      2010 in the management of headache. DESIGN: Longitudinal trends analysis. DATA:
      Nationally representative sample of visits to clinicians for headache from the
      National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical
      Care Survey, excluding visits with "red flags," such as neurologic deficit,
      cancer, or trauma. MAIN MEASURES: Use of advanced imaging (CT/MRI),
      opioids/barbiturates, and referrals to other physicians (guideline-discordant
      indicators), as well as counseling on lifestyle modifications and use of
      preventive medications including verapamil, topiramate, amitriptyline, or
      propranolol (guideline-concordant during study period). We analyzed results using
      logistic regression, adjusting for patient and clinician characteristics, and
      weighted to reflect U.S. population estimates. Additionally, we stratified
      findings based on migraine versus non-migraine, acute versus chronic symptoms,
      and whether the clinician self-identified as the primary care physician. KEY
      RESULTS: We identified 9,362 visits for headache, representing an estimated 144
      million visits during the study period. Nearly three-quarters of patients were
      female, and the mean age was approximately 46 years. Use of CT/MRI rose from 6.7%
      of visits in 1999-2000 to 13.9% in 2009-2010 (unadjusted p < 0.001), and
      referrals to other physicians increased from 6.9 % to 13.2% (p = 0.005). In
      contrast, clinician counseling declined from 23.5 % to 18.5% (p = 0.041). Use of
      preventive medications increased from 8.5 % to 15.9% (p = 0.001), while
      opioids/barbiturates remained unchanged, at approximately 18%. Adjusted trends
      were similar, as were results after stratifying by migraine versus non-migraine
      and acute versus chronic presentation. Primary care clinicians had lower odds of
      ordering CT/MRI (OR 0.56 [0.42, 0.74]). CONCLUSIONS: Contrary to numerous
      guidelines, clinicians are increasingly ordering advanced imaging and referring
      to other physicians, and less frequently offering lifestyle counseling to their
      patients. The management of headache represents an important opportunity to
      improve the value of U.S. healthcare.

PMID- 25567757
TI  - Capsule commentary on Taber et al., why do people avoid medical care? A
      qualitative study using national data.

PMID- 25567758
TI  - Nurse-led behavioral management of diabetes and hypertension in community
      practices: a randomized trial.
AB  - BACKGROUND: Several trials have demonstrated the efficacy of nurse telephone case
      management for diabetes (DM) and hypertension (HTN) in academic or vertically
      integrated systems. Little is known about the real-world potency of these
      interventions. OBJECTIVE: To assess the effectiveness of nurse behavioral
      management of DM and HTN in community practices among patients with both
      diseases. DESIGN: The study was designed as a patient-level randomized controlled
      trial. PARTICIPANTS: Participants included adult patients with both type 2 DM and
      HTN who were receiving care at one of nine community fee-for-service practices.
      Subjects were required to have inadequately controlled DM (hemoglobin A1c [A1c]
      >= 7.5%) but could have well-controlled HTN. INTERVENTIONS: All patients received
      a call from a nurse experienced in DM and HTN management once every two months
      over a period of two years, for a total of 12 calls. Intervention patients
      received tailored DM- and HTN- focused behavioral content; control patients
      received non-tailored, non-interactive information regarding health issues
      unrelated to DM and HTN (e.g., skin cancer prevention). MAIN OUTCOMES AND
      MEASURES: Systolic blood pressure (SBP) and A1c were co-primary outcomes,
      measured at 6, 12, and 24 months; 24 months was the primary time point. RESULTS:
      Three hundred seventy-seven subjects were enrolled; 193 were randomized to
      intervention, 184 to control. Subjects were 55% female and 50% white; the mean
      baseline A1c was 9.1% (SD = 1%) and mean SBP was 142 mmHg (SD = 20). Eighty-two
      percent of scheduled interviews were conducted; 69% of intervention patients and
      70% of control patients reached the 24-month time point. Expressing model
      estimated differences as (intervention--control), at 24 months, intervention
      patients had similar A1c [diff = 0.1 %, 95 % CI (-0.3, 0.5), p = 0.51] and SBP
      [diff = -0.9 mmHg, 95% CI (-5.4, 3.5), p = 0.68] values compared to control
      patients. Likewise, DBP (diff = 0.4 mmHg, p = 0.76), weight (diff = 0.3 kg, p =
      0.80), and physical activity levels (diff = 153 MET-min/week, p = 0.41) were
      similar between control and intervention patients. Results were also similar at
      the 6- and 12-month time points. CONCLUSIONS: In nine community fee-for-service
      practices, telephonic nurse case management did not lead to improvement in A1c or
      SBP. Gains seen in telephonic behavioral self-management interventions in optimal
      settings may not translate to the wider range of primary care settings.

PMID- 25567760
TI  - Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by
      overcoming the efflux function and expression of P-gp.
AB  - Venlafaxine (VLX) could be pumped out of the brain by P-glycoprotein (P-gp).
      Moreover, the expression of P-gp distributed in blood-brain barrier could be
      significantly induced by VLX. Thus, P-gp could be considered as the nature
      barrier for delivering of VLX to the brain. The aim of this study was to
      investigate whether the efflux function and increased expression of P-gp could be
      reversed by utilizing solid lipid nanoparticles (SLN). VLX solid lipid
      nanoparticles (VLX - SLN) were prepared and evaluated. Pharmacokinetics and brain
      distribution of VLX in different formulations were conducted after oral or
      intravenous administration. P-gp efflux function to VLX was evaluated by the
      brain uptake amount of VLX, while P-gp expression was investigated by Western
      blotting. Results indicated that the entrapment, mean size and zata potential of
      VLX - SLN was 74.9 +/- 3.0 %, 186.3 +/- 69.26 nm and -22.8 +/- 7.78 mv,
      respectively. After vein injection of VLX formulations, the brain uptake amount
      of VLX from VLX - SLN was significantly higher than that of VLX solution, VLX
      solution with empty SLN (VLX+ empty SLN) and VLX solution with Verapamil (VLX +
      Ver), respectively. Furthermore, the protein mass of P-gp in VLX - SLN treated
      group was the lowest among all the investigated groups. These results indicated
      that SLN could overcome P-gp and achieve brain target by intravenous
      administration.

PMID- 25567759
TI  - CD22DeltaE12 as a molecular target for corrective repair using RNA trans
      splicing: anti-leukemic activity of a rationally designed RNA trans-splicing
      molecule.
AB  - Our recent studies have demonstrated that the CD22 exon 12 deletion
      (CD22DeltaE12) is a characteristic genetic defect of therapy-refractory clones in
      pediatric B-precursor acute lymphoblastic leukemia (BPL) and implicated the
      CD22DeltaE12 genetic defect in the aggressive biology of relapsed or therapy
      refractory pediatric BPL. The purpose of the present study was to further
      evaluate the biologic significance of the CD22DeltaE12 molecular lesion and
      determine if it could serve as a molecular target for corrective repair using RNA
      trans-splicing therapy. We show that both pediatric and adult B-lineage lymphoid
      malignancies are characterized by a very high incidence of the CD22DeltaE12
      genetic defect. We provide experimental evidence that the correction of the
      CD22DeltaE12 genetic defect in human CD22DeltaE12(+) BPL cells using a rationally
      designed CD22 RNA trans-splicing molecule (RTM) caused a pronounced reduction of
      their clonogenicity. The RTM-mediated correction replaced the downstream mutation
      rich segment of Intron 12 and remaining segments of the mutant CD22 pre-mRNA with
      wildtype CD22 exons 10-14, thereby preventing the generation of the cis-spliced
      aberrant CD22DeltaE12 product. The anti-leukemic activity of this RTM against BPL
      xenograft clones derived from CD22DeltaE12(+) leukemia patients provides the
      preclinical proof-of-concept that correcting the CD22DeltaE12 defect with
      rationally designed CD22 RTMs may provide the foundation for therapeutic
      innovations that are needed for successful treatment of high-risk and relapsed
      BPL patients. 

PMID- 25567761
TI  - Phytochemical composition, protective and therapeutic effect on gastric ulcer and
      alpha-amylase inhibitory activity of Achillea biebersteinii Afan.
AB  - Three sesquiterpene lactones [two germacranolides (micranthin and sintenin) and
      one guaianolide (4beta,10alpha-dihydroxy-5beta,7beta,8betaH-guaia-1,11(13)dien
      12,8alpha-olide)] and four derivatives of 3-methoxy flavones (santin,
      quercetagetin-3,6,3'-trimethyl ether, quercetagetin-3,6-dimethyl ether, and 5,7
      dihydroxy 3,3',4'-trimethoxy flavone) were isolated from the ethyl acetate
      extract (EAE) of the aerial parts of Achillea biebersteinii Afan. (Asteraceae).
      Evaluation of protective and therapeutic effects of EAE against ethanol-induced
      gastric ulcer in rats was carried. Antiulcer activity evaluation was done through
      measuring ulcer indices, stomach acidity, gastric volume and lesion counts.
      Oxidative stress markers; malondialdehyde, glutathione and superoxide dismutase
      were also estimated. The work was extended to determine the histopathological
      assessment of the stomach. Gastric ulcer exhibited a significant elevation of the
      ulcer index and oxidative stress markers. The extract attenuated these increments
      and recorded protective and therapeutic effects against gastric ulcer.
      Hyperglycaemia increases the mucosal susceptibility to ulcerogenic stimuli and
      predisposes gastric ulceration. In vitro alpha-amylase inhibitory assay was
      applied to evaluate the post prandial antihyperglycaemia activity. The result
      showing that the EAE has the ability to reduce starch-induced postprandial
      glycaemic excursions by virtue of potent intestinal alpha-amylase inhibitory
      activity. These findings demonstrated the remarkable potential of A.
      biebersteinii as valuable source of antiulcer agent with post prandial
      hyperglycaemia lowering effect. 

PMID- 25567762
TI  - Enhancement of solubility and dissolution of cilostazol by solid dispersion
      technique.
AB  - Cilostazol is practically insoluble in water and thus results in poor
      bioavailability. Only a few approaches have been reported for improving the
      bioavailability of cilostazol. Solid dispersion technique via solvent evaporation
      method was applied to improve the solubility and dissolution of cilostazol.
      Various polymers, mixture of polymer and surfactant, and mixture of polymers were
      screened as a carrier for the solid dispersion. Solubility of cilostazol was
      improved significantly when Eudragit((r)) L100 was used as a carrier. However,
      addition of surfactant to Eudragit((r)) L100 decreased the solubility slightly.
      Whereas, the mixture of Eudragit((r)) L100 and Eudragit((r)) S100 as a carrier
      system further increased the solubility. Based on the highest solubility obtained
      among the carriers screened, 1:1 ratio of Eudragit((r)) L100 and Eudragit((r))
      S100 was selected as a carrier, and drug to carrier ratio was optimized to 1:5.
      Differential scanning calorimetry and X-ray diffraction studies showed that the
      characteristic peak of cilostazol disappeared in the solid dispersion, indicating
      that cilostazol existed in amorphous form in this formulation. Spray drying
      method was superior to vacuum drying method in terms of dissolution rate.
      Meanwhile, it was observed that the disintegration rate and the concentration of
      polymer had some effect on the crystallization of cilostazol in dissolution
      medium. Tablet formulation containing spray dried solid dispersion showed
      significant improvement in dissolution as compared to the commercial tablet.

PMID- 25567763
TI  - Altered neural reward and loss processing and prediction error signalling in
      depression.
AB  - Dysfunctional processing of reward and punishment may play an important role in
      depression. However, functional magnetic resonance imaging (fMRI) studies have
      shown heterogeneous results for reward processing in fronto-striatal regions. We
      examined neural responsivity associated with the processing of reward and loss
      during anticipation and receipt of incentives and related prediction error (PE)
      signalling in depressed individuals. Thirty medication-free depressed persons and
      28 healthy controls performed an fMRI reward paradigm. Regions of interest
      analyses focused on neural responses during anticipation and receipt of gains and
      losses and related PE-signals. Additionally, we assessed the relationship between
      neural responsivity during gain/loss processing and hedonic capacity. When
      compared with healthy controls, depressed individuals showed reduced fronto
      striatal activity during anticipation of gains and losses. The groups did not
      significantly differ in response to reward and loss outcomes. In depressed
      individuals, activity increases in the orbitofrontal cortex and nucleus accumbens
      during reward anticipation were associated with hedonic capacity. Depressed
      individuals showed an absence of reward-related PEs but encoded loss-related PEs
      in the ventral striatum. Depression seems to be linked to blunted responsivity in
      fronto-striatal regions associated with limited motivational responses for
      rewards and losses. Alterations in PE encoding might mirror blunted reward- and
      enhanced loss-related associative learning in depression. 

PMID- 25567764
TI  - Interaction of Abeta peptide with tubulin causes an inhibition of tubulin
      polymerization and the apoptotic death of cancer cells.
AB  - We report in this work that the Abeta peptide directly interacts with tubulin
      close to the vinblastine and GTP/GDP binding site, inhibits the tubulin
      polymerization rate, induces tubulin aggregation, causes cell shrinking, enhances
      Mad2, BubR1, p53, and p21 activation in MCF7 cells and induces the apoptotic
      death of A549, HeLa and MCF7 cells. 

PMID- 25567765
TI  - Effect of repetitive intra-arterial infusion of bone marrow mononuclear cells in
      patients with no-option limb ischemia: the randomized, double-blind, placebo
      controlled Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra
      arterial Supplementation (JUVENTAS) trial.
AB  - BACKGROUND: Patients with severe limb ischemia may not be eligible for
      conventional therapeutic interventions. Pioneering clinical trials suggest that
      bone marrow-derived cell therapy enhances neovascularization, improves tissue
      perfusion, and prevents amputation. The objective of this trial was to determine
      whether repetitive intra-arterial infusion of bone marrow mononuclear cells
      (BMMNCs) in patients with severe, nonrevascularizable limb ischemia can prevent
      major amputation. METHODS AND RESULTS: The Rejuvenating Endothelial Progenitor
      Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial is a
      randomized, double-blind, placebo-controlled clinical trial in 160 patients with
      severe, nonrevascularizable limb ischemia. Patients were randomly assigned to
      repetitive (3 times; 3-week interval) intra-arterial infusion of BMMNC or
      placebo. No significant differences were observed for the primary outcome, ie,
      major amputation at 6 months, with major amputation rates of 19% in the BMMNC
      versus 13% in the placebo group (relative risk, 1.46; 95% confidence interval,
      0.62-3.42). The safety outcome (all-cause mortality, occurrence of malignancy, or
      hospitalization due to infection) was not significantly different between the
      groups (relative risk, 1.46; 95% confidence interval, 0.63-3.38), neither was all
      cause mortality at 6 months with 5% versus 6% (relative risk, 0.78; 95%
      confidence interval, 0.22-2.80). Secondary outcomes quality of life, rest pain,
      ankle-brachial index, and transcutaneous oxygen pressure improved during follow
      up, but there were no significant differences between the groups. CONCLUSIONS:
      Repetitive intra-arterial infusion of autologous BMMNCs into the common femoral
      artery did not reduce major amputation rates in patients with severe,
      nonrevascularizable limb ischemia in comparison with placebo. The general
      improvement in secondary outcomes during follow-up in both the BMMNC and the
      placebo group, as well, underlines the essential role for placebo-controlled
      design of future trials. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00371371.

PMID- 25567766
TI  - Insight into the conformational stability of membrane-embedded BamA using a
      combined solution and solid-state NMR approach.
AB  - The beta-barrel assembly machinery (BAM) is involved in folding and insertion of
      outer membrane proteins in Gram-negative bacteria, a process that is still poorly
      understood. With its 790 residues, BamA presents a challenge to current NMR
      methods. We utilized a "divide and conquer" approach in which we first obtained
      resonance assignments for BamA's periplasmic POTRA domains 4 and 5 by solution
      NMR. Comparison of these assignments to solid-state NMR (ssNMR) data obtained on
      two BamA constructs including the transmembrane domain and one or two soluble
      POTRA domains suggested that the fold of POTRA domain 5 critically depends on the
      interface with POTRA 4. Using specific labeling schemes we furthermore obtained
      ssNMR resonance assignments for residues in the extracellular loop 6 that is
      known to be crucial for BamA-mediated substrate folding and insertion. Taken
      together, our data provide novel insights into the conformational stability of
      membrane-embedded, non-crystalline BamA. 

PMID- 25567767
TI  - Exploring gender differences in the working lives of UK hospital consultants.
AB  - OBJECTIVE: Internationally, increasing numbers of women are practising medicine.
      Gender differences in doctors' working hours, specialty choices and communication
      styles are well documented, but studies often neglect contextual factors such as
      the role of socialised gender expectations on behaviours in the workplace and the
      medical profession. These may be important as recent studies have reported gender
      differences in doctors' activity rates that cannot be explained by specialty or
      contracted hours, suggesting other sources of variation. This study sought to
      explore the working lives of hospital doctors and how their work is negotiated
      according to gender and context. DESIGN: Gender differences in the day-to-day
      work of hospital specialists (consultants) in the NHS were investigated using a
      qualitative approach, including observation and interview methods. Data were
      analysed inductively using qualitative observation and interview methods.
      SETTING: Two NHS hospital trusts in England. PARTICIPANTS: Data were collected
      from 13 participants working in a variety of specialties and in a range of
      clinical and non-clinical settings. MAIN OUTCOME MEASURES: Various behaviours,
      attitudes and experiences were explored, such as doctor-patient communication,
      interactions with colleagues and workload. RESULTS: Influences at both individual
      and situational levels, appear to affect differentially the work of male and
      female doctors. Female consultants described awareness of the impact of
      behaviours on relationships with colleagues, and their interactions appeared to
      be more carefully performed. Nurses and other colleagues tend to demonstrate less
      cooperation with female consultants. Gender differences also exist in patient
      communication, feelings of work-family conflict and barriers to career
      progression. CONCLUSIONS: These variations in hospital consultants' work may have
      implications for both the quantity and quality of care provided by male and
      female consultants. This is timely and of importance to the medical workforce as
      the gender composition approaches parity.

PMID- 25567768
TI  - Estimating the prevalence of aero-allergy and/or food allergy in infants,
      children and young people with moderate-to-severe atopic eczema/dermatitis in
      primary care: multi-centre, cross-sectional study.
AB  - OBJECTIVE: We sought to determine the primary care-based prevalence of moderate
      to-severe atopic eczema/dermatitis in children and to estimate what proportion
      had co-morbid aero-allergy and/or food allergy that was contributing to their
      atopic eczema/dermatitis. DESIGN: Multi-centre, cross-sectional study.
      PARTICIPANTS: Infants, children and young people aged between 0-17 years.
      SETTING: Primary Care. METHODS: General practice electronic health records were
      interrogated to identify children (0-17 years) with current moderate-to-severe
      atopic eczema/dermatitis. Eligible children were assessed by an allergy
      specialist nurse, this involving a detailed allergy history, examination and, if
      appropriate, measurement of total IgE and specific IgE to relevant aero-allergens
      and/or food allergens. MAIN OUTCOME MEASURES: Prevalence of atopic eczema,
      moderate to severe atopic eczema, IgE-mediated atopic eczema. RESULTS: We
      recruited eight practices, which together enrolled 16,877 children. Of these,
      4331 (25.7%; 95% CI 25.0, 26.3) children had a recorded diagnosis of atopic
      eczema/dermatitis and 1316 (7.8%; 95% CI 7.4, 8.2) had treatment indicative of
      current moderate-to-severe atopic eczema/dermatitis. We recruited 159 children
      for clinical assessment, and complete data were available for 157. The clinical
      assessment revealed that 130/157 (82.8%) had no indication of IgE-mediated
      allergy contributing to their atopic eczema/dermatitis; the remaining 27/157
      (17.2%; 95% CI 12.1, 23.9) were on clinical assessment considered to possibly
      have underlying IgE-mediated disease. Specific IgE tests were positive in 14/27
      (51.9%; 95% CI 34.0, 69.3) children. Of the 14 children who tested positive, six
      (42.9%; 95% CI 21.4, 67.4) were positive to food allergens and six (42.9%; 95% CI
      21.4, 67.4) to aero-allergens; the remaining two (14.3%; 95% CI 4.0, 40.0) were
      positive to both food and aero-allergens. CONCLUSIONS: Although atopic
      eczema/dermatitis is a very common diagnosis in children in primary care, most
      appear to be relatively mild and/or transient. Only a small proportion of
      children had evidence of ongoing underlying IgE-mediated atopic
      eczema/dermatitis.

PMID- 25567769
TI  - The effect of physician gender on length of patient consultations: observational
      findings from the UK hospital setting and synthesis with existing studies.
AB  - OBJECTIVES: To investigate the effect of physician gender on consultation length
      in UK hospital outpatient clinics and compare this, through meta-analysis, with
      previous studies outside the UK. DESIGN: Observational data on clinic times were
      analysed and findings were combined in a meta-analysis with existing studies
      investigating the effect of physician gender on consultation length. SETTING: UK
      hospital practice. PARTICIPANTS: A total of 174 observations of outpatient
      consultations with 10 hospital specialists (consultants) from different
      specialties in two UK hospital trusts. MAIN OUTCOME MEASURES: Clinic times were
      recorded and analysis of consultation length was undertaken with physician gender
      as a covariate. Data were then synthesised through meta-analysis with 10 existing
      studies in this field. RESULTS: No statistically significant difference was found
      in the length of consultations for male and female doctors in these UK hospital
      settings. When pooled with existing studies, consultations with women doctors
      were found to be approximately two minutes longer than with men (p = 0.01).
      CONCLUSIONS: Findings from this analysis of clinic consultations in the UK
      National Health Service do not support previous studies, which were undertaken
      predominantly in North America and primary care settings. Overall, meta-analysis
      suggests doctors' gender may influence consultation length. Gender differences in
      communication should be considered in training clinicians and in overall clinical
      practice.

PMID- 25567770
TI  - Regional differences of physical activity and sedentary behaviour in Swiss
      children are not explained by socio-demographics or the built environment.
AB  - OBJECTIVE: We evaluated whether regional differences in physical activity (PA)
      and sedentary behaviour (SB) existed along language boundaries within Switzerland
      and whether potential differences would be explained by socio-demographics or
      environmental characteristics. METHODS: We combined data of 611 children aged 4
      to 7 years from four regional studies. PA and SB were assessed by accelerometers.
      Information about the socio-demographic background was obtained by
      questionnaires. Objective neighbourhood attributes could be linked to home
      addresses. Multivariate regression models were used to test associations between
      PA and SB and socio-demographic characteristics and neighbourhood attributes.
      RESULTS: Children from the German compared to the French-speaking region were
      more physically active and less sedentary (by 10-15 %, p < 0.01). Although German
      speaking children lived in a more favourable environment and a higher
      socioeconomic neighbourhood (differences p < 0.001), these characteristics did
      not explain the differences in PA behaviour between French and German speaking.
      CONCLUSIONS: Factors related to the language region, which might be culturally
      rooted were among the strongest correlates of PA and SB among Swiss children,
      independent of individual, social and environmental factors.

PMID- 25567771
TI  - Plasma aldosterone and its relationship with left ventricular mass in
      hypertensive patients with early-stage chronic kidney disease.
AB  - Plasma aldosterone concentrations (PACs) are often increased in the advanced
      stages of chronic kidney disease (CKD); however, PAC has not been fully
      investigated in early CKD. Moreover, little is known about the relationship
      between aldosteronemia and left ventricular (LV) mass in subjects with mild-to
      moderate CKD. The study objectives were to analyze PAC, LV mass (LVM), LV
      geometry and their relationships, in a group of hypertensive patients with stage
      I-III CKD. One hundred ninety-five hypertensive patients with stage I-III CKD
      were enrolled and compared with a control group of 82 hypertensive patients
      without renal dysfunction. LVM was higher in subjects with CKD than in the
      control group and increased progressively with advancing stages of CKD (P=0.004).
      A similar trend was observed for PAC (P<0.0001), in which PAC was greater in CKD
      subjects with LV concentric geometry than in those with eccentric LV hypertrophy
      (P=0.01). Furthermore, in CKD patients, PAC was directly and significantly
      correlated with LVM (r=0.29; P<0.0001) and with relative wall thickness (RWT;
      r=0.36; P<0.0001). These associations remained significant even after adjustment
      for various confounding factors in multiple regression analyses (P<0.001). In
      summary, the results demonstrated that in CKD hypertensive patients, LVM, RWT and
      PAC are increased and related to each other from the earliest stages of renal
      dysfunction. Furthermore, it seems biologically plausible to speculate that
      aldosterone may promote a concentric geometry of the left ventricle and increase
      LVM in hypertensive patients with early CKD. 

PMID- 25567772
TI  - Can we predict the presence of coronary lesions from blood pressure measurement?
      A new clinical method.
AB  - The roles of arterial function and structure in cardiovascular physiology have
      expanded with the development of a variety of parameters that evaluate arterial
      stiffness. Markers of arterial stiffness have been correlated with cardiovascular
      outcomes. We aimed to find a simple, clinical, noninvasive method to predict
      atherosclerosis that leads to the development of coronary artery disease (CAD).
      We aimed to find a simple, clinical, noninvasive method to predict
      atherosclerosis that leads to the development of CAD. We included 100 cases that
      underwent coronary angiography in our center owing to different indications. The
      blood pressure in all cases was measured by two different observers. The
      oscillatory systolic blood pressure (OSBP) was defined as the point at which the
      mercury began to oscillate to a minimum level of 1 mm Hg. The auscultatory
      systolic blood pressure (AUSBP) was defined as the first Korotkoff sound. The
      difference between OSBP and AUSBP was calculated and called the oscillatory gap
      (OG). The correlation between the OG and the presence of coronary lesion in
      coronary angiography was statistically calculated. The study populations had a
      mean age of 57.3+/-9 years. The mean+/-s.d. OG was 14.44+/-10.44. There was a
      highly significantly positive correlation between the OG and the presence of
      coronary artery lesions (r=0.399 and P-value <0.000). There was also a
      significantly positive correlation between the presence of hypertension and the
      OG (r=0.376 and P-value <0.000). The difference between OSBP and AUSBP could be
      used as a simple method to detect atherosclerotic arterial changes. This method
      could indicate the degree of arterial stiffness. There was a significantly
      positive correlation between this new indicator of arterial stiffness and the
      presence of CAD. Any patient with a wide gap between OSBP and AUSBP should be
      treated early with antihypertensive drugs and statins before the development of
      CAD. 

PMID- 25567773
TI  - The interactions between alcohol consumption and DNA methylation of the ADD1 gene
      promoter modulate essential hypertension susceptibility in a population-based,
      case-control study.
AB  - The potential effects of the interactions between DNA methylation (CpG1 and CpG2
      5 methylation levels) of the alpha-adducin (ADD1) gene promoter and ADD1 tagSNPs
      (tag single-nucleotide polymorphisms) or the environmental factors on essential
      hypertension (EH) risk have not been clarified. Thus, we performed an age- and
      gender-matched case-control study to investigate the association between ADD1
      tagSNPs and EH. A total of 1020 subjects with EH and 1020 normotensive subjects
      were genotyped by melting temperature shift technology. Logistic regression was
      used to assess the associations of ADD1 tagSNPs, environmental factors and EH.
      The generalized multifactor dimensionality reduction (GMDR) method was applied to
      explore the potential interactions. Under additive, dominant and recessive
      models, no significant associations were evidenced between EH and rs3755885,
      rs2071694, rs4963 or rs3775067 with the complete data set or the gender
      stratified analysis after adjusting for triglycerides, body mass index and
      alcohol consumption. However, we observed a significant association between
      rs4961 and EH under the dominant model after Bonferroni correction when adjusting
      for confounding factors in the entire sample (odds ratio (OR)=0.64, 95%
      confidence interval (CI)=0.50-0.83, P=0.001). In GMDR, the two-factor interaction
      model of alcohol consumption and DNA methylation (CpG1 methylation) was the best
      model, with a maximum cross-validation consistency of 9/10 and testing balance
      accuracy of 0.63 (P=0.01). Our results indicate that the SNP rs4961 has a
      protective role in the development of EH. In conclusion, the interactions between
      alcohol consumption and DNA methylation (CpG1 methylation) of the ADD1 gene
      promoter have a significant role in modifying EH susceptibility. 

PMID- 25567774
TI  - Teriparatide treatment patterns in osteoporosis and subsequent fracture events: a
      US claims analysis.
AB  - The objective of this study was to describe the risk of fragility-related
      fractures in the 2 years following teriparatide initiation. In an administrative
      claims analysis of over 11,407 patients, approximately one in eight patients had
      a new or recurrent fragility-related fracture in the 2 years following
      teriparatide initiation. INTRODUCTION: The objective of this study was to
      describe the risk of fragility-related fractures in the 2 years following the
      initiation of teriparatide in a real-world setting. METHODS: This retrospective
      study used data from the 2002 to 2011 MarketScan(r) Commercial and Medicare
      Supplemental Databases to identify patients 50 years and older with a diagnosis
      of osteoporosis (ICD-9-CM code 733.0x) who were initiating teriparatide. Patients
      were required to have continuous medical and pharmacy benefit coverage for the 12
      months prior to and 24 months following teriparatide initiation (index event).
      Teriparatide treatment patterns (persistence and adherence) were described, as
      was the use of antiresorptive therapy. The primary study outcome was the presence
      of a new or recurring fragility fracture following the initiation of
      teriparatide. RESULTS: A total of 11,407 patients met the study criteria (mean
      age = 69.5, standard deviation = 10.6 years; 92.0% female). One in four (25.6%)
      patients had fragility fracture claims in the year prior to teriparatide
      initiation, of which 64.0% were on existing antiresorptive therapy. Overall,
      13.4% (n = 1527) of patients had a new or recurrent fracture during the 2-year
      follow-up period. Forty-eight percent of patients on teriparatide treatment were
      considered persistent; fragility fractures were more common among patients
      nonpersistent with teriparatide (15.2%) than among those persistent with
      teriparatide (11.4%). A higher fracture rate (35.7%) was observed in the cohort
      with previous fragility fracture then those without pre-index fractures (24%).
      CONCLUSION: More than 13.4% of patients had new or recurrent fragility-related
      fractures during the 2 years following the initiation of teriparatide; these
      fractures were more in common in patients with pre-existing fractures and the
      patients who were nonpersistent with teriparatide.

PMID- 25567776
TI  - Screening for and treatment of osteoporosis: construction and validation of a
      state-transition microsimulation cost-effectiveness model.
AB  - This study aimed to document and validate a new cost-effectiveness model of
      osteoporosis screening and treatment strategies. The state-transition
      microsimulation model demonstrates strong internal and external validity. It is
      an important tool for researchers and policy makers to test the cost
      effectiveness of osteoporosis screening and treatment strategies. INTRODUCTION:
      The objective of this study was to document and validate a new cost-effectiveness
      model of screening for and treatment of osteoporosis. METHODS: A state-transition
      microsimulation model using a lifetime horizon was constructed with seven Markov
      states (no history of fractures, hip fracture, vertebral fracture, wrist
      fracture, other fracture, postfracture state, and death) describing the most
      important clinical outcomes of osteoporotic fractures. Tracker variables were
      used to record patients' history, such as fracture events, duration of treatment,
      and time since last screening. The model was validated for Chinese postmenopausal
      women receiving screening and treatment versus no screening. Goodness-of-fit
      analyses were performed for internal and external validation. External validity
      was tested by comparing life expectancy, osteoporosis prevalence rate, and
      lifetime and 10-year fracture risks with published data not used in the model.
      RESULTS: The model represents major clinical facets of osteoporosis-related
      conditions. Age-specific hip, vertebral, and wrist fracture incidence rates were
      accurately reproduced (the regression line slope was 0.996, R(2) = 0.99). The
      changes in costs, effectiveness, and cost-effectiveness were consistent with
      changes in both one-way and probabilistic sensitivity analysis. The model
      predicted life expectancy and 10-year any major osteoporotic fracture risk at the
      age of 65 of 19.01 years and 13.7%, respectively. The lifetime hip, clinical
      vertebral, and wrist fracture risks at age 50 were 7.9, 29.8, and 18.7%
      respectively, all consistent with reported data. CONCLUSIONS: Our model
      demonstrated good internal and external validity, ensuring it can be confidently
      applied in economic evaluations of osteoporosis screening and treatment
      strategies.

PMID- 25567778
TI  - History of the official publication of the Japanese Society of Gastroenterology:
      from Gastroenterologia Japonica to Journal of Gastroenterology.

PMID- 25567775
TI  - Bone quality in osteopenic postmenopausal women is not improved after 12 months
      of whole-body vibration training.
AB  - Whole-body vibration training may improve bone quality through structural
      adaptation. We tested if 12 months of training affects bone structure in
      osteopenic postmenopausal women by using advanced 3-dimensional high-resolution
      imaging techniques. We found that whole-body vibration training did not improve
      bone structure compared to inactive controls. INTRODUCTION: Whole-body vibration
      training (WBVT) has been suggested as a preventive measure against bone loss.
      Contradicting results of previous studies may be confounded by insufficiently
      sensitive bone density measures to detect relevant bone changes. WBVT may improve
      bone quality through structural adaptations, without increasing bone mineral
      density (BMD). We hypothesized that 12 months of WBVT will improve or maintain
      bone microarchitecture and bone strength in osteopenic postmenopausal women.
      METHODS: Twenty-two women received WBVT for 2-3 sessions/week and were compared
      with 20 controls. Bone outcomes were measured by high-resolution peripheral
      quantitative CT (HR-pQCT, XtremeCT, Scanco Medical) and finite element estimated
      bone strength. Balance and jump performance and maximum voluntary contraction
      (MVC) of knee flexor and extensor muscles were recorded. All measurements were
      taken at baseline, 4, 8, and 12 months and a reduced data set at 4 and 8 months
      follow-up and compared using a mixed model repeated measures ANOVA. RESULTS:
      Thirty-one women completed the study with 90 % compliance (WBVT: n = 17, control
      n = 14). Total BMD (p < 0.001), cortical area*(p = 0.004), cortical thickness (p
      = 0.011), and cortical porosity (p = 0.024) all significantly decreased over time
      in both groups; WBVT did not affect the response. All other bone outcomes were
      not affected by WBVT or time. No difference in measures of balance, jump height,
      and MVC due to WBVT were detected. CONCLUSION: In our cohort, WBVT did not lead
      to improved bone quality in postmenopausal osteopenic women after 12 months of
      training compared to controls, and there were no detected benefits related to
      balance and muscle strength outcomes.

PMID- 25567777
TI  - Analysis of daily teriparatide treatment for osteoporosis in men.
AB  - The percent and absolute lumbar spine and femoral neck bone mineral densities and
      absolute procollagen type I N-terminal propeptide (PINP) increases following a 20
      MUg/day teriparatide treatment for 12 months were similar in men and women
      regardless of sex differences. INTRODUCTION: Several placebo-controlled studies
      have measured the effects of daily teriparatide in men and postmenopausal women
      with osteoporosis but none have directly compared the effects between these
      groups. We retrospectively compared the effects of daily teriparatide therapy in
      men and postmenopausal women with osteoporosis and investigated biochemical
      markers of bone turnover to detect possible sex differences. METHODS: Patients
      (563; 75 men and 488 women) with osteoporosis were retrospectively investigated.
      All patients were administered with teriparatide at 20 MUg/day for 12 months. The
      primary efficacy measure was changed in lumbar spine (LS) and femoral neck (FN)
      bone mineral density (BMD) after 12 months of treatment. The change in serum
      levels of procollagen type I N-terminal propeptide (PINP) and urinary N
      telopeptide (uNTX) excretion after 4, 8 and 12 months of treatment were also
      measured. RESULTS: In men, the percent LS BMD significantly increased by 11.3 +/-
      9.9 % (mean +/- standard deviation (SD)) and the FN BMD increased by 0.4 +/- 6.4
      % without a significant difference at 12 months. In postmenopausal women, the
      percent LS BMD significantly increased by 9.6 +/- 8.1 % and the FN BMD
      significantly increased by 2.4 +/- 7.8 % at 12 months. The percent and absolute
      BMD increases in LS and FN between men and women were similar. The absolute
      increases in PINP were similar in both groups at 4, 8 and 12 months. However, the
      absolute increases in uNTX were significantly lower in men than in women at 8 and
      12 months. CONCLUSION: Daily teriparatide treatment was as effective in men as in
      postmenopausal women regardless of sex differences.

PMID- 25567779
TI  - Europium-doped LaF3 nanocrystals with organic 9-oxidophenalenone capping ligands
      that display visible light excitable steady-state blue and time-delayed red
      emission.
AB  - Visible light excitable and color tunable ~5% Eu(3+)-doped LaF3 nanocrystals
      (NCs), containing 9-oxidophenalenone ligands bound to the surface as visible
      light sensitizers for Eu(3+) dopants, have been synthesized by a facile solution
      based method. The crystalline phase structure, size, composition, morphology and
      luminescence properties of the NCs are characterized using X-ray diffraction,
      high-resolution transmission electron microscopy, energy dispersive X-ray
      spectroscopy, and steady-state and time-resolved emission spectroscopy. The
      results show that these NCs are very small in size (<10 nm), display high degree
      of crystallinity and have pure tysonite structure of LaF3 with P3[combining
      macron]c1 space group. The visible light excitation of the capping ligands
      triggers an alternate display of steady-state, short-lived blue emission (tau < 1
      ns) and time-delayed, long-lived sensitized red Eu(3+) emission (tau = 0.41 ms),
      allowing photoluminescence chromacity tuning as a function of delay time within a
      specific inorganic composition. The visible light sensitization of the dopant
      Eu(3+) sites proves more efficient than direct excitation of 5% Eu(3+)-doped LaF3
      NCs capped by citrate ligands. The dopant Eu(3+) ions are well protected from non
      radiative deactivation through high-energy vibrations of the organic capping
      ligands which is proved by the long lifetime of the sensitized Eu(3+) emission.
      The time-resolved emission spectra collected over a period of several
      milliseconds reveal that the dopant Eu(3+) ions occupy at least three different
      sites in the NC host. It is further inferred that the sensitized Eu(3+) emission
      primarily comes from surface dopant sites and sites just underneath the surface
      of the NCs. We propose that some of the interior Eu(3+) sites also display
      sensitized emission, which are indirectly populated via Eu(3+) -> Eu(3+) energy
      migration from surface-sensitized Eu(3+) sites of the NCs. 

PMID- 25567781
TI  - Consequences of the REDOXS and METAPLUS Trials: The End of an Era of Glutamine
      and Antioxidant Supplementation for Critically Ill Patients?

PMID- 25567780
TI  - The telehealth skills, training, and implementation project: an evaluation
      protocol.
AB  - BACKGROUND: Telehealth appears to be an ideal mechanism for assisting rural
      patients and doctors and medical students/registrars in accessing specialist
      services. Telehealth is the use of enhanced broadband technology to provide
      telemedicine and education over distance. It provides accessible support to rural
      primary care providers and medical educators. A telehealth consultation is where
      a patient at a general practice, with the assistance of the general practitioner
      or practice nurse, undertakes a consultation by videoconference with a specialist
      located elsewhere. Multiple benefits of telehealth consulting have been reported,
      particularly those relevant to rural patients and health care providers. However
      there is a paucity of research on the benefits of telehealth to medical education
      and learning. OBJECTIVE: This protocol explains in depth the process that will be
      undertaken by a collaborative group of universities and training providers in
      this unique project. METHODS: Training sessions in telehealth consulting will be
      provided for participating practices and students. The trial will then use
      telehealth consulting as a real-patient learning experience for students, general
      practitioner trainees, general practitioner preceptors, and trainees. RESULTS:
      Results will be available when the trial has been completed in 2015. CONCLUSIONS:
      The protocol has been written to reflect the overarching premise that, by
      building virtual communities of practice with users of telehealth in medical
      education, a more sustainable and rigorous model can be developed. The Telehealth
      Skills Training and Implementation Project will implement and evaluate a
      theoretically driven model of Internet-facilitated medical education for
      vertically integrated, community-based learning environments.

PMID- 25567782
TI  - A Patient With Parenteral Nutrition-Dependent Short Bowel Syndrome and
      Cardiovascular Disease With 4-Year Exposure to Teduglutide.
AB  - Clinical trials of the glucagon-like peptide 2 analogue teduglutide resulted in
      approval of the drug by the Food and Drug Administration in 2012 as a treatment
      for parenteral nutrition-dependent short bowel syndrome in adults. This report
      presents the case study of a man with short bowel syndrome caused by portal vein
      thrombosis who had 4 years exposure to the drug at the time of his death due to
      cardiovascular disease.

PMID- 25567783
TI  - Still a Place for Metoclopramide as a Prokinetic Drug in Critically Ill Patients?

PMID- 25567784
TI  - Use of Temporary Enteral Access Devices in Hospitalized Neonatal and Pediatric
      Patients in the United States.
AB  - BACKGROUND: Temporary enteral access devices (EADs), such as nasogastric (NG),
      orogastric (OG), and postpyloric (PP), are used in pediatric and neonatal
      patients to administer nutrition, fluids, and medications. While the use of these
      temporary EADs is common in pediatric care, it is not known how often these
      devices are used, what inpatient locations have the highest usage, what size tube
      is used for a given weight or age of patient, and how placement is verified per
      hospital policy. MATERIALS AND METHODS: This was a multicenter 1-day prevalence
      study. Participating hospitals counted the number of NG, OG, and PP tubes present
      in their pediatric and neonatal inpatient population. Additional data collected
      included age, weight and location of the patient, type of hospital, census for
      that day, and the method(s) used to verify initial tube placement. RESULTS: Of
      the 63 participating hospitals, there was an overall prevalence of 1991 temporary
      EADs in a total pediatric and neonatal inpatient census of 8333 children (24%
      prevalence). There were 1316 NG (66%), 414 were OG (21%), and 261 PP (17%) EADs.
      The neonatal intensive care unit (NICU) had the highest prevalence (61%),
      followed by a medical/surgical unit (21%) and pediatric intensive care unit
      (18%). Verification of EAD placement was reported to be aspiration from the tube
      (n = 21), auscultation (n = 18), measurement (n = 8), pH (n = 10), and X-ray (n =
      6). CONCLUSION: The use of temporary EADs is common in pediatric care. There is
      wide variation in how placement of these tubes is verified.

PMID- 25567786
TI  - Relaxation and Simplex mathematical algorithms applied to the study of steady
      state electrochemical responses of immobilized enzyme biosensors: Comparison with
      experiments.
AB  - A description of the implementation of the relaxation method with automatic mesh
      point allocation for immobilized enzyme electrodes is presented. The advantages
      of this method for the solution of coupled reaction-diffusion problems are
      discussed. The relaxation numerical simulation technique is combined with the
      Simplex fitting algorithm to extract kinetic parameters from experimental data.
      The results of the simulations are compared to experimental data from self
      assembled multilayered electrodes comprised of glucose oxidase (GOx) and an Os
      modified redox mediator and found to be in excellent agreement.

PMID- 25567785
TI  - Challenging the 48-Hour Rule-Out for Central Line-Associated Bloodstream
      Infections in the Pediatric Intestinal Failure Population: A Retrospective Pilot
      Study.
AB  - INTRODUCTION: While parenteral nutrition (PN) has revolutionized the management
      of patients with intestinal failure (IF), central line-associated bloodstream
      infections (CLABSIs) remain a leading cause of mortality and morbidity in this
      population. The objective of this study is to characterize the presentation of
      CLABSIs in pediatric IF and to determine the time to positivity of blood
      cultures. METHODS: A retrospective cohort study of children with IF who presented
      to our institution for evaluation of a possible CLABSI from January 1, 2012, to
      December 31, 2012, was performed. RESULTS: Sixty patients with IF were
      identified. There were 33 cases of CLABSI in 16 patients, with a rate of 1.5
      infections per 1000 catheter days. There were no significant differences in age,
      growth parameters, or catheter days between patients with or without CLABSI.
      Fever was documented in 85% of patients with CLABSI. These patients demonstrated
      an increased percentage of neutrophils and higher C-reactive protein levels
      compared with patients without CLABSI. The mean time to culture positivity was
      13.2 hours, and 97% of cultures were positive within 24 hours. CONCLUSION: Our
      data suggest that most pediatric patients with IF who have CLABSI develop
      positive cultures within 24 hours, and the absence of fever and leukocytosis does
      not necessarily indicate the absence of infection. These findings may support
      clinical practice guidelines in favor of shorter hospital stay when CLABSI is
      suspected; however, a prospective analysis of CLABSI in this population is
      recommended to determine the safety and appropriate setting prior to any practice
      change.

PMID- 25567787
TI  - Management of pump thrombosis in patients with left ventricular assist devices.
AB  - The gradual evolution of left ventricular assist device (LVAD) therapy has
      resulted in a durable option for patients as either a bridge to transplantation
      (BTT) or a destination therapy (DT). Outcomes with current continuous-flow
      devices continue to demonstrate significant patient benefit, not only in enhanced
      survival but also in improved functional capacity and quality of life. While the
      lessening of adverse events through time has resulted in more widespread adoption
      of this therapy, there continues to be unintended consequences, including, most
      notably, infection, bleeding, and thrombosis. Beginning in 2011, centers and
      collaborative groups began to observe a significant increase in the incidence of
      pump thrombosis with the HeartMate II LVAD (Thoratec Corp., Pleasanton, CA, USA).
      However, this clinical scourge is not limited to the HeartMate II, as the
      HeartWare Ventricular Assist System (HVAD; HeartWare Inc., Framingham, MA, USA)
      has also had these same issues, which led to pump modifications and the
      appreciation of more strict control of blood pressure and anticoagulation with
      this pump design. We review the current status of the field of mechanical
      circulatory support in its approach to diagnosis, management, and prevention of
      LVAD pump thrombosis. 

PMID- 25567788
TI  - Erratum to: Thiazide-like/calcium channel blocker agents: a major combination for
      hypertension management.

PMID- 25567789
TI  - Ventricular dysrhythmias associated with poisoning and drug overdose: a 10-year
      review of statewide poison control center data from California.
AB  - BACKGROUND: Ventricular dysrhythmias are a serious consequence associated with
      drug overdose and chemical poisoning. The risk factors for the type of
      ventricular dysrhythmia and the outcomes by drug class are not well documented.
      OBJECTIVE: The aim of this study was to determine the most common drugs and
      chemicals associated with ventricular dysrhythmias and their outcomes. METHODS:
      We reviewed all human exposures reported to a statewide poison control system
      between 2002 and 2011 that had a documented ventricular dysrhythmia. Cases were
      differentiated into two groups by type of arrhythmia: (1) ventricular
      fibrillation and/or tachycardia (VT/VF); and (2) torsade de pointes (TdP).
      RESULTS: Among the 300 potential cases identified, 148 cases met the inclusion
      criteria. Of these, 132 cases (89%) experienced an episode of VT or VF, while the
      remaining 16 cases (11%) had an episode of TdP. The most commonly involved
      therapeutic classes of drugs associated with VT/VF were antidepressants (33/132,
      25%), stimulants (33/132, 25%), and diphenhydramine (16/132, 12.1%). Those
      associated with TdP were antidepressants (4/16, 25%), methadone (4/16, 25%), and
      antiarrhythmics (3/16, 18.75%). Drug exposures with the greatest risk of death in
      association with VT/VF were antidepressant exposure [odds ratio (OR) 1.71; 95%
      confidence interval (CI) 0.705-4.181] and antiarrhythmic exposure (OR 1.75; 95%
      CI 0.304-10.05), but neither association was statistically significant. Drug
      exposures with a statistically significant risk for TdP included methadone and
      antiarrhythmic drugs. CONCLUSIONS: Antidepressants and stimulants were the most
      common drugs associated with ventricular dysrhythmias. Patients with suspected
      poisonings by medications with a high risk of ventricular dysrhythmia warrant
      prompt ECG monitoring.

PMID- 25567790
TI  - Mitofusin 2 as a driver that controls energy metabolism and insulin signaling.
AB  - SIGNIFICANCE: Mitochondrial dynamics is a complex process that impacts on
      mitochondrial biology. RECENT ADVANCES: Recent evidence indicates that proteins
      participating in mitochondrial dynamics have additional cellular roles. Mitofusin
      2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on
      energy metabolism in muscle, liver, and hypothalamic neurons. In addition, Mfn2
      is subjected to tight regulation. Hence, factors such as proinflammatory
      cytokines, lipid availability, or glucocorticoids block its expression, whereas
      exercise and increased energy expenditure promote its upregulation. CRITICAL
      ISSUES: Importantly, Mfn2 controls cell metabolism and insulin signaling by
      limiting reactive oxygen species production and by modulation of endoplasmic
      reticulum stress. In this connection, it is critical to understand precisely the
      molecular mechanisms involved in the global actions of Mfn2. FUTURE DIRECTIONS:
      Future directions should concentrate into the analysis of those mechanisms, and
      to fully demonstrate that Mfn2 represents a cellular hub that senses the
      metabolic and hormonal milieu and drives the control of metabolic homeostasis.

PMID- 25567791
TI  - Cognitive function in adults aging with fabry disease: a case-control feasibility
      study using telephone-based assessments.
AB  - We examined the feasibility of recruiting US adults >=45 years old with Fabry
      disease (FD) for telephone assessments of cognitive functioning. A case-control
      design matched each FD participant on age, sex, race, and education to four
      participants from a population-based study. Fifty-four participants with FD age
      46-72 years were matched to 216 controls. Standardized cognitive assessments,
      quality of life (QOL), and medical histories were obtained by phone, supplemented
      by objective indices of comorbidities. Normalized scores on six cognitive tasks
      were calculated. On the individual tasks, scores on list recall and semantic
      fluency were significantly lower among FD participants (p-values < 0.05), while
      scores on the other four tasks did not differ. After averaging each participant's
      normalized scores to form a cognitive composite, we examined group differences in
      composite scores, before and after adjusting for multiple covariates using
      generalized estimating equations. The composite scores of FD cases were
      marginally lower than controls before covariate adjustments (p = 0.08). QOL and
      mental health variables substantially attenuated this finding (p = 0.75),
      highlighting the influence of these factors on cognition in FD. Additional
      adjustment for cardiovascular comorbidities, kidney function, and stroke had
      negligible impact, despite higher prevalence in the FD sample. Telephone-based
      cognitive assessment methods are feasible among adults with FD, affording access
      to a geographically dispersed sample. Although decrements in discrete cognitive
      domains were observed, the overall cognitive function of older adults with FD was
      equivalent to that of well-matched controls before and after accounting for
      multiple confounding variables. 

PMID- 25567792
TI  - Reference range for thyrotropin. Post hoc assessment.
AB  - Setting the reference range for thyrotropin (TSH) remains a matter of ongoing
      controversy. PATIENTS, METHODS: We used an indirect method to determine the TSH
      reference range post hoc in a large sample. A total of 399 well characterised
      subjects showing no evidence of thyroid dysfunction were selected for definition
      of the TSH reference limits according to the method of Katayev et al.. To this
      end, the cumulative frequency was plotted against the individual logarithmic TSH
      values. Reference limits were calculated by extrapolating the middle linear part
      of the regression line to obtain the cut-offs for the 95% confidence interval. We
      also examined biological variation in a sample of 65 subjects with repeat
      measurements to establish reference change values (RCVs). RESULTS: Based on
      these, the reference interval obtained by the novel technique was in close
      agreement with the conventionally established limits, but differed significantly
      from earlier recommendations. DISCUSSION: Following unverified recommendations
      could result in a portion of patients with subclinical thyroid dysfunctions being
      missed, an important consideration in a setting with a high prevalence of thyroid
      autonomy. CONCLUSION: Indirect post hoc verification of reference intervals from
      a large retrospective sample is a modern approach that gives plausible results.
      The method seems particularly useful to assess the adequacy and performance of
      reference limits reported or established by others in a particular setting. The
      present data should encourage re-evaluation of reference systems on a broader
      scale.

PMID- 25567793
TI  - Periodic limb movements during sleep are associated with a lower quality of life
      in children with monosymptomatic nocturnal enuresis.
AB  - The study investigates whether cortical arousals and periodic limb movements
      during sleep are related to daytime psychological functioning in children with
      monosymptomatic nocturnal enuresis with associated nocturnal polyuria.
      Psychological functioning is evaluated on five domains: attention deficit
      hyperactivity disorder-inattentive problems, quality of life, internalizing
      problems, externalizing problems, and executive functioning. This multi-informant
      (parents, teachers, and children) and multi-method study included overnight video
      polysomnography, questionnaires, and neuropsychological testing. Thirty children
      (7 girls) 6 to 16 years (mean 10.43 years, SD 3.08) were selected in a tertiary
      enuresis center. A high index of periodic limb movements during sleep was
      associated with a lower quality of life, according to the child. No significant
      correlations were found with attention deficit hyperactivity disorder-inattentive
      problems, internalizing problems, externalizing problems, and executive
      functioning. CONCLUSION: This study clarifies the relationship between sleep
      parameters and psychological functioning of the children with monosymptomatic
      nocturnal enuresis and associated nocturnal polyuria according to the child, the
      parents, and the teachers. Periodic limb movements during sleep are associated
      with a lower quality of life of the child.

PMID- 25567794
TI  - The effects of estradiol on mood and behavior in human female adolescents: a
      systematic review.
AB  - Mood disorders and health risk behaviors increase in adolescence. Puberty is
      considered to contribute to these events. However, the precise impact of pubertal
      hormone changes to the emergence of mood disorders and risk behaviors is
      relatively unclear. It is important that inappropriate attribution is not made.
      Our aim was to determine what is known about the effect of endogenous estradiol
      on human adolescent girls' mood and behavior. The databases searched were
      MEDLINE, Embase, PsycINFO, Education Resources Information Center (ERIC), Pre
      MEDLINE, Web of Science, and Scopus for all dates to October 2014. For inclusion,
      contemporaneous hormone and mood or behavioral assessment was required. Data were
      extracted following a template created by the authors. Fourteen studies met our
      inclusion criteria. There was some consistency in findings for mood and estradiol
      levels, with associations between estradiol and depression and emotional tone and
      risk taking. Results were less consistent for studies assessing other mood and
      behavioral outcomes. Most studies were cross-sectional in design; assay
      methodologies used in older studies may lack the precision to detect early
      pubertal hormone levels. CONCLUSION: Three longitudinal and several cross
      sectional studies indicate potential associations between estradiol and certain
      mood or affective states, especially depression and mood variability though there
      are insufficient data to confirm that the rise in estradiol during puberty is
      causative. We believe that it is important for health professionals to take care
      when attributing adolescent psychopathology to puberty hormones, as the current
      data supporting these assertions are limited.

PMID- 25567796
TI  - Unforeseen high temperature and humidity stability of FeCl3 intercalated few
      layer graphene.
AB  - We present the first systematic study of the stability of the structure and
      electrical properties of FeCl3 intercalated few-layer graphene to high levels of
      humidity and high temperature. Complementary experimental techniques such as
      electrical transport, high resolution transmission electron microscopy and Raman
      spectroscopy conclusively demonstrate the unforseen stability of this transparent
      conductor to a relative humidity up to 100% at room temperature for 25 days, to a
      temperature up to 150 degrees C in atmosphere and to a temperature as high as 620
      degrees C in vacuum, that is more than twice higher than the temperature at which
      the intercalation is conducted. The stability of FeCl3 intercalated few-layer
      graphene together with its unique values of low square resistance and high
      optical transparency, makes this material an attractive transparent conductor in
      future flexible electronic applications. 

PMID- 25567795
TI  - An insight into the relationships between prohepcidin, iron deficiency anemia,
      and interleukin-6 values in pediatric Helicobacter pylori gastritis.
AB  - The link between Helicobacter pylori and iron deficiency (ID) or iron deficiency
      anemia (IDA) has been investigated recently. We suggested that IDA/ID associated
      with H. pylori infection might be mediated by inflammation-driven hepcidin
      production. Patients with complaints of recurrent abdominal pain and dyspepsia
      aged between 7-16 years were included in this study. Patients were divided into
      two groups according to H. pylori status in upper gastrointestinal endoscopy.
      Group I who had H. pylori gastritis (n=50) received triple antibiotic therapy.
      Group II (n=50) who had H. pylori-negative gastritis only received proton pump
      inhibitor. Thirty healthy children with the similar age and gender were included
      in the study as a control group. Complete blood count, serum iron levels, iron
      binding capacity, ferritin levels, prohepcidin and interleukin-6 (IL-6) values
      were evaluated in all children at the first visit. Initial tests were repeated
      after H. pylori eradication. Initial levels of ferritin (p=0.002), prohepcidin
      (p=0.003), and IL-6 (p=0.004) were found significantly lower in group I compared
      to group II and the control group. The mean prohepcidin level was lower in the
      anemic H. pylori-positive group than in non-anemic H. pylori-positive group;
      however, the difference was not statistically significant. While significant
      increases in hematocrit and mean corpuscular volume were observed, no significant
      difference was found in serum ferritin, prohepcidin, or IL-6 level after
      eradication treatment in H. pylori-positive group. CONCLUSION: H. pylori-induced
      gastritis appears to cause an increase in prohepcidin levels and a decrease in
      ferritin levels, supporting our hypothesis; but this relationship has not been
      proven.

PMID- 25567797
TI  - Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic
      hepatitis B and C.
AB  - Persistent infections with hepatitis B virus (HBV) or hepatitis C virus (HCV)
      account for the majority of cases of hepatic cirrhosis and hepatocellular
      carcinoma (HCC) worldwide. Small, non-coding RNAs play important roles in virus
      host interactions. We used high throughput sequencing to conduct an unbiased
      profiling of small (14-40 nts) RNAs in liver from Japanese subjects with advanced
      hepatitis B or C and hepatocellular carcinoma (HCC). Small RNAs derived from
      tRNAs, specifically 30-35 nucleotide-long 5' tRNA-halves (5' tRHs), were abundant
      in non-malignant liver and significantly increased in humans and chimpanzees with
      chronic viral hepatitis. 5' tRH abundance exceeded microRNA abundance in most
      infected non-cancerous tissues. In contrast, in matched cancer tissue, 5' tRH
      abundance was reduced, and relative abundance of individual 5' tRHs was altered.
      In hepatitis B-associated HCC, 5' tRH abundance correlated with expression of the
      tRNA-cleaving ribonuclease, angiogenin. These results demonstrate that tRHs are
      the most abundant small RNAs in chronically infected liver and that their
      abundance is altered in liver cancer.

PMID- 25567799
TI  - Seed supply for broadscale restoration: maximizing evolutionary potential.
AB  - Restoring degraded land to combat environmental degradation requires the
      collection of vast quantities of germplasm (seed). Sourcing this material raises
      questions related to provenance selection, seed quality and harvest
      sustainability. Restoration guidelines strongly recommend using local sources to
      maximize local adaptation and prevent outbreeding depression, but in highly
      modified landscapes this restricts collection to small remnants where limited,
      poor quality seed is available, and where harvesting impacts may be high. We
      review three principles guiding the sourcing of restoration germplasm: (i) the
      appropriateness of using 'local' seed, (ii) sample sizes and population
      characteristics required to capture sufficient genetic diversity to establish
      self-sustaining populations and (iii) the impact of over-harvesting source
      populations. We review these topics by examining current collection guidelines
      and the evidence supporting these, then we consider if the guidelines can be
      improved and the consequences of not doing so. We find that the emphasis on local
      seed sourcing will, in many cases, lead to poor restoration outcomes,
      particularly at broad geographic scales. We suggest that seed sourcing should
      concentrate less on local collection and more on capturing high quality and
      genetically diverse seed to maximize the adaptive potential of restoration
      efforts to current and future environmental change. 

PMID- 25567798
TI  - How well can captive breeding programs conserve biodiversity? A review of
      salmonids.
AB  - Captive breeding programs are increasingly being initiated to prevent the
      imminent extinction of endangered species and/or populations. But how well can
      they conserve genetic diversity and fitness, or re-establish self-sustaining
      populations in the wild? A review of these complex questions and related issues
      in salmonid fishes reveals several insights and uncertainties. Most programs can
      maintain genetic diversity within populations over several generations, but
      available research suggests the loss of fitness in captivity can be rapid, its
      magnitude probably increasing with the duration in captivity. Over the long-term,
      there is likely tremendous variation between (i) programs in their capacity to
      maintain genetic diversity and fitness, and (ii) species or even intraspecific
      life-history types in both the severity and manner of fitness-costs accrued.
      Encouragingly, many new theoretical and methodological approaches now exist for
      current and future programs to potentially reduce these effects. Nevertheless, an
      unavoidable trade-off exists between conserving genetic diversity and fitness in
      certain instances, such as when captive-bred individuals are temporarily released
      into the wild. Owing to several confounding factors, there is also currently
      little evidence that captive-bred lines of salmonids can or cannot be
      reintroduced as self-sustaining populations. Most notably, the root causes of
      salmonid declines have not been mitigated where captive breeding programs exist.
      Little research has also addressed under what conditions an increase in
      population abundance due to captive-rearing might offset fitness reductions
      induced in captivity. Finally, more empirical investigation is needed to evaluate
      the genetic/fitness benefits and risks associated with (i) maintaining captive
      broodstocks as either single or multiple populations within one or more
      facilities, (ii) utilizing cryopreservation or surrogate broodstock technologies,
      and (iii) adopting other alternatives to captive-rearing such as translocations
      to new habitats. Management recommendations surrounding these issues are
      proposed, with the aim of facilitating meta-analyses and more general principles
      or guidelines for captive-breeding. These include the need for the following: (i)
      captive monitoring to involve, a priori, greater application of hypothesis
      testing through the use of well-designed experiments and (ii) improved
      documentation of procedures adopted by specific programs for reducing the loss of
      genetic diversity and fitness. 

PMID- 25567800
TI  - Latitudinal variation in cold hardiness in introduced Tamarix and native Populus.
AB  - To investigate the evolution of clinal variation in an invasive plant, we
      compared cold hardiness in the introduced saltcedar (Tamarix ramosissima, Tamarix
      chinensis, and hybrids) and the native plains cottonwood (Populus deltoides
      subsp. monilifera). In a shadehouse in Colorado (41 degrees N), we grew plants
      collected along a latitudinal gradient in the central United States (29-48
      degrees N). On 17 occasions between September 2005 and June 2006, we determined
      killing temperatures using freeze-induced electrolyte leakage and direct
      observation. In midwinter, cottonwood survived cooling to -70 degrees C, while
      saltcedar was killed at -33 to -47 degrees C. Frost sensitivity, therefore, may
      limit northward expansion of saltcedar in North America. Both species
      demonstrated inherited latitudinal variation in cold hardiness. For example, from
      September through January killing temperatures for saltcedar from 29.18 degrees N
      were 5-21 degrees C higher than those for saltcedar from 47.60 degrees N, and on
      September 26 and October 11, killing temperatures for cottonwood from 33.06
      degrees N were >43 degrees C higher than those for cottonwood from 47.60 degrees
      N. Analysis of nine microsatellite loci showed that southern saltcedars are more
      closely related to T. chinensis while northern plants are more closely related to
      T. ramosissima. Hybridization may have introduced the genetic variability
      necessary for rapid evolution of the cline in saltcedar cold hardiness. 

PMID- 25567801
TI  - Male mating strategy and the introgression of a growth hormone transgene.
AB  - Escaped transgenic organisms (GMO's) may threaten the populations of their wild
      relatives if able to hybridize with each other. The introgression of a growth
      enhancement transgene into a wild Atlantic salmon population may be affected by
      the transgene's effects not only on fitness parameters, but also on mating
      behaviour. Large anadromous GMO males are most preferred in mating, but a
      transgene can also give the large sneakers a reproductive advantage over the
      smaller wild individuals. With a simulation model, we studied whether the
      increase in the proportion and mating success of sneakers in transgenic and
      hybrid genotypes could facilitate the introgression of a transgene into wild
      population after the release of GMOs. The model combines population dynamics and
      Mendelian inheritance of a transgenic trait. We found that the introgression of
      the transgene is strongly affected by the greater mating preference of large GMO
      males. Furthermore, the difference in reproductive success between the anadromous
      versus sneaker strategy defines how much GMO's have to be preferred to be able to
      invade. These results emphasize the importance of detailed knowledge of
      reproductive systems and the effect of a transgene on the phenotype and behaviour
      of GMOs when assessing the consequences of their release or escape to the wild. 

PMID- 25567802
TI  - Applications of graph theory to landscape genetics.
AB  - We investigated the relationships among landscape quality, gene flow, and
      population genetic structure of fishers (Martes pennanti) in ON, Canada. We used
      graph theory as an analytical framework considering each landscape as a network
      node. The 34 nodes were connected by 93 edges. Network structure was
      characterized by a higher level of clustering than expected by chance, a short
      mean path length connecting all pairs of nodes, and a resiliency to the loss of
      highly connected nodes. This suggests that alleles can be efficiently spread
      through the system and that extirpations and conservative harvest are not likely
      to affect their spread. Two measures of node centrality were negatively related
      to both the proportion of immigrants in a node and node snow depth. This suggests
      that central nodes are producers of emigrants, contain high-quality habitat
      (i.e., deep snow can make locomotion energetically costly) and that fishers were
      migrating from high to low quality habitat. A method of community detection on
      networks delineated five genetic clusters of nodes suggesting cryptic population
      structure. Our analyses showed that network models can provide system-level
      insight into the process of gene flow with implications for understanding how
      landscape alterations might affect population fitness and evolutionary potential.

PMID- 25567805
TI  - Response: on the consequences of sexual selection for fisheries-induced
      evolution.

PMID- 25567804
TI  - Comment: On the consequences of sexual selection for fisheries-induced evolution.
AB  - It is becoming increasingly recognized that fishing (and other forms of nonrandom
      harvesting) can have profound evolutionary consequences for life history traits.
      A recent and welcome publication provided the first description of how sexual
      selection might influence the outcome of fisheries-induced evolution (FIE). One
      of the main conclusions was that if sexual selection generates a positive
      relationship between body size and reproductive success, increased fishing
      pressure on large individuals causes stronger selection for smaller body size.
      Here, we re-evaluate the sexual selection interpretation of the relationship
      between body size and reproductive success, and suggest it may in fact be
      representative of a more general case of pure natural selection. The consequences
      of sexual selection on FIE are likely to be complicated and dynamic, and we
      provide additional perspectives to these new and exciting results. Selection
      differentials and trait variance are considered, with density-dependent and
      genetic effects on the strength and the direction of sexual selection given
      particular attention. We hope that our additional views on the role of sexual
      selection in FIE will encourage more theoretical and empirical work into this
      important application of evolutionary biology. 

PMID- 25567806
TI  - The X-ray structure of the primary adducts formed in the reaction between
      cisplatin and cytochrome c.
AB  - In the present study, the interactions between cisplatin and cytochrome c are
      investigated. Based on high-resolution X-ray diffraction data, two monometalated
      species, i.e. cyt c-Pt(NH3)2 and cyt c-Pt(NH3)2Cl, are found to be the main
      adducts that form in the reaction between the protein and the drug. Both
      monodentate and bidentate platinum coordination to the protein is observed, with
      platinum binding either to Met65 or to Met65 and Glu61, simultaneously. 

PMID- 25567803
TI  - Exploring the origin and degree of genetic isolation of Anopheles gambiae from
      the islands of Sao Tome and Principe, potential sites for testing transgenic
      based vector control.
AB  - The evolutionary processes at play between island and mainland populations of the
      malaria mosquito vector Anopheles gambiae sensu stricto are of great interest as
      islands may be suitable sites for preliminary application of transgenic-based
      vector control strategies. Sao Tome and Principe, located off the West African
      coast, have received such attention in recent years. This study investigates the
      degree of isolation of An. gambiae s.s. populations between these islands and the
      mainland based on mitochondrial and ribosomal DNA molecular data. We identify
      possible continental localities from which these island populations derived. For
      these purposes, we used F ST values, haplotype networks, and nested clade
      analysis to estimate migration rates and patterns. Haplotypes from both markers
      are geographically widespread across the African continent. Results indicate that
      the populations from Sao Tome and Principe are relatively isolated from
      continental African populations, suggesting they are promising sites for test
      releases of transgenic individuals. These island populations are possibly derived
      from two separate continental migrations. This result is discussed in the context
      of the history of the African slave trade with respect to Sao Tome and Principe. 

PMID- 25567807
TI  - Impact of ER stress-regulated ATF4/p16 signaling on the premature senescence of
      renal tubular epithelial cells in diabetic nephropathy.
AB  - Premature senescence is an important event during diabetic nephropathy (DN)
      progression. Here, we investigated the role of endoplasmic reticulum (ER) stress
      regulated activation of transcription factor 4 (ATF4)/p16 signaling in the
      premature senescence of renal tubular epithelial cells (RTECs) during DN
      development. In the renal tissues of Type 2 DN patients, we detected an increased
      number of senescent cells; elevated deposition of advanced glycation end products
      (AGEs); upregulated expression of ER stress marker, glucose-regulated protein 78;
      as well as overexpression of ATF4 and p16. Similarly, these phenomena were also
      observed in cultured mouse RTECs following AGE treatment. Interestingly, AGE
      induced p16 expression and premature senescence were successfully attenuated by
      ER stress inhibitor and ATF4 gene silencing. Moreover, AGE-induced premature
      senescence was mimicked by ER stress inducers and ATF4 overexpression, while
      suppressed by p16 gene silencing. In addition, ER stress inducers can augment
      ATF4 expression. Therefore, our results demonstrate that the ER stress-regulated
      ATF4/p16 pathway is involved in the premature senescence of RTECs during DN
      progression. 

PMID- 25567808
TI  - Molecular determinants of force production in human skeletal muscle fibers:
      effects of myosin isoform expression and cross-sectional area.
AB  - Skeletal muscle contractile performance is governed by the properties of its
      constituent fibers, which are, in turn, determined by the molecular interactions
      of the myofilament proteins. To define the molecular determinants of contractile
      function in humans, we measured myofilament mechanics during maximal Ca(2+)
      activated and passive isometric conditions in single muscle fibers with
      homogenous (I and IIA) and mixed (I/IIA and IIA/X) myosin heavy chain (MHC)
      isoforms from healthy, young adult male (n = 5) and female (n = 7) volunteers.
      Fibers containing only MHC II isoforms (IIA and IIA/X) produced higher maximal
      Ca(2+)-activated forces over the range of cross-sectional areas (CSAs) examined
      than MHC I fibers, resulting in higher (24-42%) specific forces. The number
      and/or stiffness of the strongly bound myosin-actin cross bridges increased in
      the higher force-producing MHC II isoforms and, in all isoforms, better predicted
      force than CSA. In men and women, cross-bridge kinetics, in terms of myosin
      attachment time and rate of myosin force production, were independent of CSA,
      although women had faster (7-15%) kinetics. The relative proportion of cross
      bridges and/or their stiffness was reduced as fiber size increased, causing a
      decline in specific force. Results from our examination of molecular mechanisms
      across the range of physiological CSAs explain the variation in specific force
      among the different fiber types in human skeletal muscle, which may have
      relevance to understanding how various physiological and pathophysiological
      conditions modulate single-fiber and whole muscle contractility. 

PMID- 25567812
TI  - Frontiers in lipid research.

PMID- 25567811
TI  - Fine-tuning innate and adaptive immune responses: another KLFhanger. Focus on
      "Kruppel-like factor KLF10 regulates transforming growth factor receptor II
      expression and TGF-beta signaling in CD8+ T lymphocytes".

PMID- 25567813
TI  - Adapting to a changing environment in research, education, and technology.

PMID- 25567814
TI  - Practical, office-based interventions that improve care today.
AB  - This issue is devoted to practical information and interventions to enhance
      patient care. Fully explaining the richness of the articles to our readers in a
      short Editors' Note is sometimes difficult. This month we were struck by the
      large number of specific interventions that could be used directly in practice
      today, or in the near future, because they do not require much additional time or
      much additional cost. These interventions do require some learning-and perhaps
      some unlearning-but readers can use this issue to make changes tomorrow! We would
      love to hear from any readers who use this information and implement one or
      another of the actions; send your stories to jabfm@med.wayne.edu. 

PMID- 25567810
TI  - Myopathic changes in murine skeletal muscle lacking synemin.
AB  - Diseases of striated muscle linked to intermediate filament (IF) proteins are
      associated with defects in the organization of the contractile apparatus and its
      links to costameres, which connect the sarcomeres to the cell membrane. Here we
      study the role in skeletal muscle of synemin, a type IV IF protein, by examining
      mice null for synemin (synm-null). Synm-null mice have a mild skeletal muscle
      phenotype. Tibialis anterior (TA) muscles show a significant decrease in mean
      fiber diameter, a decrease in twitch and tetanic force, and an increase in
      susceptibility to injury caused by lengthening contractions. Organization of
      proteins associated with the contractile apparatus and costameres is not
      significantly altered in the synm-null. Elastimetry of the sarcolemma and
      associated contractile apparatus in extensor digitorum longus myofibers reveals a
      reduction in tension consistent with an increase in sarcolemmal deformability.
      Although fatigue after repeated isometric contractions is more marked in TA
      muscles of synm-null mice, the ability of the mice to run uphill on a treadmill
      is similar to controls. Our results suggest that synemin contributes to linkage
      between costameres and the contractile apparatus and that the absence of synemin
      results in decreased fiber size and increased sarcolemmal deformability and
      susceptibility to injury. Thus synemin plays a moderate but distinct role in fast
      twitch skeletal muscle. 

PMID- 25567809
TI  - Inhibition of RhoA-dependent pathway and contraction by endogenous hydrogen
      sulfide in rabbit gastric smooth muscle cells.
AB  - Inhibitory neurotransmitters, chiefly nitric oxide and vasoactive intestinal
      peptide, increase cyclic nucleotide levels and inhibit muscle contraction via
      inhibition of myosin light chain (MLC) kinase and activation of MLC phosphatase
      (MLCP). H2S produced as an endogenous signaling molecule synthesized mainly from
      l-cysteine via cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase
      (CBS) regulates muscle contraction. The aim of this study was to analyze the
      expression of CSE and H2S function in the regulation of MLCP activity, 20-kDa
      regulatory light chain of myosin II (MLC20) phosphorylation, and contraction in
      isolated gastric smooth muscle cells. Both mRNA expression and protein expression
      of CSE, but not CBS, were detected in smooth muscle cells of rabbit, human, and
      mouse stomach. l-cysteine, an activator of CSE, and NaHS, a donor of H2S,
      inhibited carbachol-induced Rho kinase and PKC activity, Rho kinase-sensitive
      phosphorylation of MYPT1, PKC-sensitive phosphorylation of CPI-17, and MLC20
      phosphorylation and sustained muscle contraction. The inhibitory effects of l
      cysteine, but not NaHS, were blocked upon suppression of CSE expression by siRNA
      or inhibition of its activity by dl-propargylglycine (PPG) suggesting that the
      effect of l-cysteine is mediated via activation of CSE. Glibenclamide, an
      inhibitor of KATP channels, had no effect on the inhibition of contraction by
      H2S. Both l-cysteine and NaHS had no effect on basal cAMP and cGMP levels but
      augmented forskolin-induced cAMP and SNP-induced cGMP formation. We conclude that
      both endogenous and exogenous H2S inhibit muscle contraction, and the mechanism
      involves inhibition of Rho kinase and PKC activities and stimulation of MLCP
      activity leading to MLC20 dephosphorylation and inhibition of muscle contraction.

PMID- 25567816
TI  - Solo practitioners remain important contributors to primary care.

PMID- 25567817
TI  - Fewer family physicians are in solo practices.
AB  - Over the past 20 years there has been a statistically significant trend toward
      fewer family physicians identifying as being in solo practice. Further study to
      determine the reasons for this decline and its impact on access to care will be
      critical because rural areas are more dependent on solo practitioners. 

PMID- 25567819
TI  - The effects of myofascial trigger point injections on nocturnal calf cramps.
AB  - BACKGROUND: The purpose of this study was to elucidate the effects of injection
      at trigger points on pain and sleep disturbance in patients with nocturnal calf
      cramps (NCCs). METHODS: Patients with NCCs that occurred at least once per week
      and who had myofascial trigger points (MTrPs) on the gastrocnemius muscles were
      enrolled in the study for 9 months. At the first visit (T0), we measured the
      intensity of NCC pain on an 11-point numeric rating scale, recorded the frequency
      of NCCs, and calculated the Insomnia Severity Index (ISI). We then checked for
      MTrPs on the gastrocnemius muscles and injected 1-2 mL of 0.25% lidocaine into
      each of the trigger points. At 1 (T1), 2 (T2), and 4 (T3) weeks after the first
      visit, we repeated the process performed at T0. RESULTS: Twelve patients
      completed the treatment schedule and attended the follow-up visits. Mean values
      of the numeric rating scale pain score, frequency of cramps, and ISI declined
      significantly at T1, T2, and T3 compared with baseline (all P < .01). Of 12
      patients, 10 had clinical insomnia before treatment, and this number decreased
      significantly to 3 patients at T2 and 1 patient at T3 (P = .012 and P = .001,
      respectively). CONCLUSIONS: These preliminary data show that injection at MTrPs
      in patients with NCCs not only alleviated pain and reduced the frequency of
      cramps but also lessened the severity of insomnia as measured by the ISI. A
      larger randomized controlled trial is needed to confirm these findings and
      determine whether the effect lasts over the long term.

PMID- 25567818
TI  - BREATHE OUT: a randomized controlled trial of a structured intervention to
      improve clinician satisfaction with "difficult" visits.
AB  - PURPOSE: Difficult patients comprise at least 15% of ambulatory visits and are
      associated with clinician burnout. No structured procedure has been reported to
      assist health care practitioners with these challenging relationships. This
      randomized trial evaluated whether a pre- and postvisit patient-centered and
      clinician-reflective technique called BREATHE OUT improved clinician satisfaction
      during visits with patients perceived by the clinician as difficult. METHODS: Six
      family medicine residency clinics paired as urban, suburban, and rural sites were
      randomized by clinic to the BREATHE OUT intervention or usual care of difficult
      patients. A total of 57 physician faculty, nurse practitioners, physician
      assistants, and residents participated. The validated Physician Satisfaction
      Scale (PSS) was administered and analyzed using hierarchical linear modeling to
      assess differences between the intervention and control groups. RESULTS: The
      BREATHE OUT intervention improved the PSS score (P = .02) in the intervention
      group compared with the usual care group. Female practitioners reported worse PSS
      scores compared with their male counterparts despite whether they used BREATHE
      OUT (P = .009). CONCLUSIONS: Application of the BREATHE OUT questionnaire before
      and after visits improved clinician satisfaction with difficult patient
      encounters.

PMID- 25567820
TI  - The effect of regular primary care utilization on long-term glycemic and blood
      pressure control in adults with diabetes.
AB  - PURPOSE: Complications of diabetes mellitus (DM) can be reduced with regular
      preventive care and guidance on self-management. We investigated whether regular
      primary care utilization could improve glycemic control and blood pressure
      control among American Indian/Alaska Native people with DM. METHODS: Patient
      characteristics, risk factors, and health outcomes were identified from
      electronic health records of a cohort of 2138 adults with DM who received care
      between 1995 and 2010 from Southcentral Foundation, a tribal provider. Bivariate
      probit regression models estimated the probability of glycemic control and blood
      pressure control as functions of regular primary care, risk factors, and access
      factors, while taking into account potential bias arising from voluntarily
      choosing to seek primary care services. RESULTS: Regular primary care was
      associated with an 89% increased likelihood of blood pressure control (95%
      confidence interval [CI], 59-118%) and 177% increased likelihood of glycemic
      control (95% CI, 123-222%). Increasing the distance by 10 miles to primary care
      services reduced the likelihood of regular primary care by 3.7% (95% CI, -2.9% to
      -4.6%). CONCLUSIONS: Regular primary care utilization over 16 years was
      associated with higher rates of blood pressure control and glycemic control for
      adults with DM. People living closer to primary care services had a better chance
      of improved outcomes.

PMID- 25567821
TI  - The impact of health coaching on medication adherence in patients with poorly
      controlled diabetes, hypertension, and/or hyperlipidemia: a randomized controlled
      trial.
AB  - BACKGROUND: Lack of concordance between medications listed in the medical record
      and taken by the patient contributes to poor outcomes. We sought to determine
      whether patients who received health coaching by medical assistants improved
      their medication concordance and adherence. METHODS: This was a nonblinded,
      randomized, controlled, pragmatic intervention trial. English- or Spanish
      speaking patients, age 18 to 75 years, with poorly controlled type 2 diabetes,
      hypertension, and/or hyperlipidemia were enrolled from 2 urban safety net clinics
      and randomized to receive 12 months of health coaching versus usual care.
      RESULTS: Outcomes included concordance between medications documented in the
      medical record and those reported by the patient and adherence based on the
      patient-reported number of days (of the last 7) on which patient took all
      prescribed medications. The proportion of medications completely concordant
      increased in the coached group versus the usual care group (difference in change,
      10%; P = .05). The proportion of medications listed in the chart but not taken
      significantly decreased in the coached group compared with the usual care group
      (difference in change, 17%; P = .013). The mean number of adherent days increased
      in the coached but not in the usual care group (difference in change, 1.08; P <
      .001). CONCLUSIONS: Health coaching by medical assistants significantly increases
      medication concordance and adherence.

PMID- 25567822
TI  - Improving breast and colon cancer screening rates: a comparison of letters,
      automated phone calls, or both.
AB  - PURPOSE: Low-cost interventions to improve cancer screening among primary care
      patients are needed. The comparative effectiveness of personalized letters,
      automated telephone calls, and both on breast cancer (BC) and colorectal cancer
      (CRC) screening is not known. METHODS: A pragmatic, randomized, controlled trial
      was conducted in 2011 to 2012. Eligible primary care patients were women ages 50
      to 74 years who were past due for mammography and men or women who were past due
      for mammography or CRC screening of any kind (>12 months since last fecal occult
      blood test, >5 years since last sigmoidoscopy/double-contrast barium enema, or
      >10 years since last colonoscopy), respectively. Participants were randomized to
      1 of 3 interventions: personalized mailed letters, automated telephone calls, or
      both. The primary outcome was medical record documentation of a completed
      mammogram or CRC screening within 36 weeks of randomization. We estimated the
      costs of each intervention and calculated the marginal cost-effectiveness per
      person screened. RESULTS: The crude screening rates for BC were 19%, 22%, and 37%
      and for CRC were 17%, 14%, and 24% for the letter, automated call, and combined
      (letter/automated call) groups, respectively. The combined intervention group had
      a statistically higher screening rate (P < .05) compared with either of the
      single intervention groups (letter only or automated call) for both BC and CRC in
      both the crude and adjusted analyses. The combined intervention costs $5.11 per
      additional person screened for BC and $13.14 per additional person screened for
      CRC. CONCLUSION: In a primary care practice, letters plus automated telephone
      calls are better than either alone in increasing cancer screening rates among
      patients who are overdue for screening. These findings suggest the promise of a
      relatively inexpensive intervention to improve cancer screening.

PMID- 25567823
TI  - Fundamental issues in implementing an ambulatory care electronic health record.
AB  - BACKGROUND: The use of a fully functional electronic health record (EHR) system
      is linked to improved quality measures. However, almost half of ambulatory
      providers with an EHR do not use the full functionality. Attempts to encourage
      optimal use of EHRs must address barriers associated with the need to change
      medical practice. METHODS: Our primary research question was, what are the
      fundamental issues associated with the need to change medical practice that
      created barriers to electronic health record (EHR) implementation and use? In
      this qualitative study we analyzed the data from 47 interviews with
      administrative and physician informants and 6 focus groups including 35
      practicing physicians across 6 health care organizations that were deemed to be
      successful with ambulatory EHR implementation. RESULTS: Comments from informants
      revealed 6 fundamental issues: (1) need to change practice style; (2) threat to
      professionalism; (3) shift of expertise; (4) required changes to interactions
      with patients; (5) concern about the impact on medical education and training;
      and (6) concern about effects on clinical care. CONCLUSION: The physician
      experience must be at the forefront of efforts to increase the rate of ambulatory
      physician use of the full functionalities of an EHR. The issues highlighted here
      illuminate potential points of intervention when engaging physicians to ensure
      optimal use of EHRs.

PMID- 25567824
TI  - Monitoring suicidal patients in primary care using electronic health records.
AB  - INTRODUCTION: Patients at risk for suicide often come into contact with primary
      care providers, many of whom use electronic health records (EHRs) for charting.
      It is not known, however, how often suicide ideation or attempts are documented
      in EHRs. METHODS: We used retrospective analyses of de-identified EHR data from a
      distributed health network of primary care organizations to estimate the
      frequency of using diagnostic codes to record suicidal ideation and attempts.
      Data came from 3 sources: a clinician notes field processed using natural
      language processing; a suicidal ideation item on a patient-reported depression
      severity instrument (9-item Patient Health Questionnaire [PHQ-9]); and diagnostic
      codes from the EHR. RESULTS: Only 3% of patients with an indication of suicidal
      ideation in the notes field had a corresponding International Classification of
      Diseases, 9th Revision (ICD-9), code (kappa = 0.036). Agreement between an
      indication of suicidal ideation from item 9 of the PHQ-9 and an ICD-9 code was
      slightly higher (kappa = 0.068). Suicide attempt indicated in the notes field was
      more likely to be recorded using an ICD-9 code (19%; kappa = 0.18). CONCLUSIONS:
      Few cases of suicidal ideation and attempt were documented in patients' EHRs
      using diagnostic codes. Increased documentation of suicidal ideation and
      behaviors in patients' EHRs may improve their monitoring in the health care
      system.

PMID- 25567826
TI  - Intrapartum antibiotics and childhood atopic dermatitis.
AB  - INTRODUCTION: Atopic dermatitis (AD) in children significantly impacts families
      because of medical costs, "lost" hours, and secondary characteristics such as
      asthma and ancillary infections. We investigate whether children delivered
      vaginally to women receiving intrapartum antibiotics have a greater risk of AD
      when younger than the age of 2 years than their counterparts. METHODS: We
      conducted a retrospective analysis of women who delivered child(ren) vaginally
      between 1996 and 2008. Women were identified as those who received intrapartum
      antibiotics and those who did not. Pediatric records were used to determine the
      incidence of AD. RESULTS: We collected data for 492 mother-child pairs.
      Intrapartum antibiotics were administered during 128 births; 28.9% of those
      children were diagnosed with AD by age 2 years (relative risk [RR], 1.03; 95%
      confidence interval [CI], 0.75-1.41). Factors with the greatest risk of diagnosis
      of AD by 2 years of age were intrapartum antibiotic exposure for >24 hours (RR,
      1.99; 95% CI, 1.13-3.49), first born (RR, 1.78; 95% CI, 1.33-2.38), and higher
      maternal education (RR, 1.43; 95% CI, 0.99-2.06). No statistical differences in
      the prevalence of AD related to parental eczema, maternal group B Streptococcus
      status, or gestational age existed. CONCLUSIONS: Exposure to antibiotics for <24
      hours during a vaginal delivery does not increase the risk of AD. Studies are
      needed to understand whether exposure for >24 hours during the intrapartum period
      increases the risk of AD.

PMID- 25567827
TI  - Gastric bypass may promote weight loss in overweight partners.
AB  - INTRODUCTION: Following bariatric surgery, patients are expected to implement
      diet and lifestyle changes that may be imitated by cohabitating family members.
      We hypothesize that cohabitating family members will lose weight and improve
      their eating behavior within 1 year after surgery. METHODS: In this observational
      prospective study, family members of patients who had gastric bypass surgery (88
      partners, 20 children >=18 years old, and 25 children between 12 and 17 years
      old) were repeatedly assessed. Family members were asked to assess their weight
      and height before and 3, 6, and 12 months following bariatric surgery, and they
      filled out the Dutch Eating Behavior Questionnaire. RESULTS: Between baseline and
      1 year following surgery, 49 partners of patients who underwent gastric bypass
      surgery (66.2%) lost weight, 6 (8.1%) remained stable, and 19 (25.7%) gained
      weight. Body mass index of partners (P = .002), particularly of overweight
      partners (P < .001)-but not children-showed a small, significant decrease over
      time. No significant changes in eating behavior among partners or children were
      found. CONCLUSION: The study indicates that gastric bypass surgery may have a
      ripple effect, with body weight in partners of patients decreasing over time.
      However, there is considerable variation in the postoperative weight loss of
      partners.

PMID- 25567825
TI  - Comparable sustained virologic suppression between community- and academic-based
      HIV care settings.
AB  - PURPOSE: The human immunodeficiency virus (HIV)/acquired immunodeficiency
      syndrome epidemic in the United States is evolving because of factors such as
      aging and geographic diffusion. Provider shortages are also driving the
      restructuring of HIV care delivery away from specialized settings, and family
      medicine providers may play a larger role in the future. We attempted to compare
      the effectiveness of HIV treatment delivered at community versus hospital care
      settings. METHODS: The outcome of interest was sustained virologic suppression
      defined as 2 consecutive HIV-1 RNA measurements <=400 copies/mL within 1 year
      after antiretroviral initiation. We used data from the multistate HIV Research
      Network cohort to compare sustained virologic suppression outcomes among 15,047
      HIV-infected adults followed from 2000 to 2008 at 5 community- and 8 academic
      hospital-based ambulatory care sites. Community-based sites were mostly staffed
      by family medicine and general internal medicine physicians with HIV expertise,
      whereas hospital sites were primarily staffed by infectious disease
      subspecialists. Multivariate mixed effects logistic regression controlling for
      potential confounding variables was applied to account for clustering effects of
      study sites. RESULTS: In an unadjusted analysis the rate of sustained virologic
      suppression was significantly higher among subjects treated in community-based
      care settings: 1,646 of 2,314 (71.1%) versus 8,416 of 12,733 (66.1%) (P < .01).
      In the adjusted multivariate model with potential confounding variables, the rate
      was higher, although not statistically significant, in the community-based
      settings (adjusted odds ratio, 1.26; 95% confidence interval, 0.73-2.16).
      CONCLUSION: Antiretroviral therapy can be delivered effectively through community
      based treatment settings. This finding is potentially important for new program
      development, shifting HIV care into community-based settings as the landscape of
      accountable care, health reform, and HIV funding and resources evolves.

PMID- 25567828
TI  - Patient factors associated with documented provision of JNC 7-recommended
      hypertension care at an academic family medicine office.
AB  - BACKGROUND: Little is known about patient factors associated with the provision
      of hypertension care as recommended by JNC 7. METHODS: We conducted a
      retrospective chart review (n = 150) to compare documented provision of items
      recommended by JNC 7 with various patient factors, using a 15-point scoring tool
      (0% to 100%). RESULTS: The overall documentation of JNC guideline-recommended
      care was 78.3%. There was a significant effect of marital status; married
      patients received more guideline-recommended care than unmarried patients (80.4%
      vs 74.4%; P = .02). Men received more guideline-recommended care than women
      (80.7% vs 76.4%; P = .02). Multivariate analysis revealed that Medicaid patients
      had 7.1% lower rates of guideline-recommended care than patients with other
      insurance (P = .05). There was no significant difference in guideline-recommended
      care based on race/ethnicity; however, racial/ethnic disparities were identified
      for certain individual standards. CONCLUSIONS: Hypertension care in 2013 at an
      academic family medicine center was, for the most part, in agreement with
      guidelines; however, provision of some items varied based on sex, marital status,
      and insurance. Awareness of these predictors may help improve the implementation
      of guidelines, particularly relevant given the recent release of JNC 8.

PMID- 25567829
TI  - Provision of family planning to women with cardiovascular risk factors.
AB  - BACKGROUND: Cardiovascular risk factors (CVRFs) in reproductive-aged women can
      lead to pregnancy complications and fetal anomalies. METHODS: We performed a
      cross-sectional analysis using data from the National Ambulatory Medical Care
      Survey, 2009-2010. The study sample included visits by reproductive-aged women
      with CVRFs diabetes, hypertension, hyperlipidemia, obesity, or tobacco use. The
      comparison group was visits by reproductive-aged women with no chronic disease.
      Family planning action was defined as counseling, medication, or procedure.
      RESULTS: Among an estimated 223,407,070 ambulatory visits, 30.8% were associated
      with at least 1 CVRF, and 17.2% had at least 1 family planning action. There was
      no increased frequency of family planning for visits by women with CVRFs compared
      with those with no chronic disease (17.4% vs 17.1%, respectively). In the
      multivariable model, the odds ratio (OR) of a woman with a CVRF receiving family
      planning was 1.2 (95% confidence interval [CI], 0.9-1.5). Visits for preventive
      care (OR, 2.3; 95% CI, 1.8-3.1), as well as gynecologic and sexual health care
      (OR, 2.6; 95% CI, 1.9-3.7), were significantly associated with increased odds of
      family planning. CONCLUSION: There are low rates of family planning during visits
      by reproductive-aged women overall, with no significant difference for visits by
      women with CVRFs. Comprehensive preventive visits in primary care may especially
      benefit women of reproductive age with CVRFs, reducing the risk of poor pregnancy
      outcomes.

PMID- 25567830
TI  - Rate of urinary retention in adults with down syndrome: a prospective study.
AB  - PURPOSE: Down syndrome (DS) is associated with a higher incidence of many medical
      conditions, but little information regarding urinary retention exists. We
      assessed the urinary retention rates in a group of adults with DS and compared
      the characteristics of patients with and without urinary retention. METHODS: A
      prospective observational study of adults with DS was conducted. Patients were
      recruited at their regularly scheduled medical appointments. A noninvasive
      bladder volume instrument, the BladderScan BVI 3000, was used to determine the
      bladder volume after voiding. RESULTS: We enrolled 66 patients (mean age, 36.6
      years). Of these, 6 patients (9%) had urinary retention. Patients with urinary
      retention were significantly older (46.5 vs 35.6 years old; P = .022) and had
      higher rates of urinary frequency (P = .003) than patients without urinary
      retention. No other differences were statistically significant. Of the 6 patients
      with urinary retention, most (83.3%) were men and 45 years of age or older.
      Urinary frequency was the most common symptom associated with the diagnosis of
      urinary retention. CONCLUSIONS: The reported frequency and symptoms of urinary
      retention in adults with DS who are older than 45 years of age can be used to
      guide further clinical evaluation for urinary retention.

PMID- 25567831
TI  - An iPhone-assisted particle repositioning maneuver for benign paroxysmal
      positional vertigo (BPPV): a prospective randomized study.
AB  - PURPOSE: The Epley particle repositioning maneuver (PRM) is an effective
      treatment for benign paroxysmal positional vertigo (BPPV), the most common cause
      of peripheral vertigo in primary care settings. The goal of this study was to
      determine whether the use of an iPhone application (DizzyFIX; Clearwater Clinical
      Ltd, Ottawa, Ontario, Canada) by medical students had a significant impact on the
      performance of the PRM. METHODS: We recruited senior medical students who had
      previously been trained in the management of BPPV and asked them to perform the
      PRM on a healthy volunteer. One half of the students used a real iPhone
      application, whereas the others used a sham application. The PRM performance
      scores of the 2 groups were compared. RESULTS: iPhone application users scored
      significantly higher on their PRM performance compared with controls (P < .0001)
      and performed the PRM significantly more slowly (P < .0001). CONCLUSIONS: Senior
      medical students performed a more correct PRM when assisted by the iPhone
      application. This application represents a significant improvement from standard
      medical school training using written instructions. Family physicians could also
      use this iPhone application for the quick and effective treatment of BPPV.

PMID- 25567832
TI  - Birth history is forever: implications for family medicine.
AB  - The rapidly growing number of adult survivors of preterm birth has necessitated
      and made possible for the first time large-scale investigations of long-term
      outcomes of preterm birth. Large epidemiologic studies have shown that the long
      term sequelae are wide-ranging, including metabolic disorders, cardiovascular and
      respiratory disease, psychiatric disorders, and increased mortality risk.
      Clinicians should now recognize preterm birth as a long-term, multidisease risk
      factor in adults. These research findings contribute to a growing body of
      evidence of early life programming for chronic disease, which in turn supports a
      "life course" paradigm for patient care. Family medicine is an ideally conceived
      discipline for this paradigm because of its unique role in caring for patients
      across the entire life span. As our understanding of early life influences on
      long-term health continues to advance, family physicians are ideally positioned
      to incorporate this knowledge into clinical practice. 

PMID- 25567834
TI  - Diagnosis and management of upper gastrointestinal bleeding in children.
AB  - Upper gastrointestinal bleeding is an uncommon but potentially serious, life
      threatening condition in children. Rapid assessment, stabilization, and
      resuscitation should precede all diagnostic modalities in unstable children. The
      diagnostic approach includes history, examination, laboratory evaluation,
      endoscopic procedures, and imaging studies. The clinician needs to determine
      carefully whether any blood or possible blood reported by a child or adult
      represents true upper gastrointestinal bleeding because most children with true
      upper gastrointestinal bleeding require admission to a pediatric intensive care
      unit. After the diagnosis is established, the physician should start a proton
      pump inhibitor or histamine 2 receptor antagonist in children with upper
      gastrointestinal bleeding. Consideration should also be given to the initiation
      of vasoactive drugs in all children in whom variceal bleeding is suspected. An
      endoscopy should be performed once the child is hemodynamically stable. 

PMID- 25567833
TI  - Improvement in lung cancer outcomes with targeted therapies: an update for family
      physicians.
AB  - In the past decade the advent of target therapy has led to a silent revolution in
      the treatment of lung cancer. Thanks to the specificity of their target, new
      tailored drugs are able to achieve a larger benefit and lower toxicity and
      provide better quality of life than cytotoxic drugs in a limited number of
      patients, selected by molecular profile. Nowadays, the epidermal growth factor
      receptor tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic
      lymphoma kinase inhibitor crizotinib, are targeted agents approved for treatment
      of non-small-cell lung cancer. Family physicians play an important role in the
      treatment, detection, and management of common toxicities and in providing
      emotional support. Therefore this review integrates molecular profile assessment
      with evidence of the efficacy and toxicity of tyrosine kinase inhibitors to
      provide an updated overview of the treatment of non-small-cell lung cancer, which
      radically changed after the advent of targeted therapies. It also aims to promote
      a more intensive and interactive collaboration between specialists and family
      physicians in the management of all phases of cancer care. 

PMID- 25567835
TI  - A rare case of neck pain: acute longus colli calcific tendinitis in a possibly
      immunocompromised individual.
AB  - We present a rare case of severe neck pain in a 45-year-old man with severe
      hidradenitis suppurativa who was participating in a study involving adalimumab.
      The neck pain was associated with acute longus colli calcific tendinitis, which
      is a noninfectious inflammatory response in the longus colli tendons secondary to
      deposition of calcium hydroxyapatite crystal. The diagnosis was made by computed
      tomography, which showed calcifications and deposits, and magnetic resonance
      imaging, which showed a retropharyngeal effusion. Ears, Nose, and Throat Services
      performed a fiberoptic scope examination, which revealed a patent airway and no
      drainable abscess. Nonsteroidal anti-inflammatory drugs resulted in a dramatic
      improvement in the patient's clinical symptoms. In acute longus colli tendinitis,
      differentiating retropharyngeal aseptic effusion from infection is important. Of
      note, the confounding factor in this case was that the patient was blinded to
      whether he was receiving the placebo or adalimumab, so whether the patient was
      immunosuppressed and at risk for infection was unknown. Clinician familiarity and
      education concerning acute calcific longus colli tendinitis may lead to decreased
      costs stemming from incorrect diagnosis and unnecessary treatment. 

PMID- 25567836
TI  - Staphylococcus epidermidis in urine is not always benign: a case report of
      pyelonephritis in a child.
AB  - PURPOSE: Staphylococcus epidermidis in urine cultures from previously healthy
      children is usually considered to be a contaminant. The goal of this study was to
      identify cases in which S. epidermidis was an infectious cause of urinary tract
      infection (UTI) in children. METHODS: A literature search identified 7 cases, 6
      of which were previously published and 1 which was unpublished, described herein.
      RESULTS: S. epidermidis was identified as the causative organism of UTIs in
      children with underlying urinary tract abnormalities. CONCLUSION: UTIs caused by
      S. epidermidis in a previously healthy child should not be disregarded as a
      contaminant and further workup for urinary tract abnormality is indicated.

PMID- 25567837
TI  - Low-dose quetiapine induced or worsened mania in the context of possible
      undertreatment.
AB  - Bipolar disorder is a mental illness with a lifetime prevalence of 2% and has a
      dramatic impact on quality of life. Mania is a distinct period of abnormal and
      sustained elevated, expansive, or irritable mood and increase in goal-directed
      activity or energy that lasts at least 1 week and is present for most of each
      day. Quetiapine is an atypical antipsychotic approved for the treatment of
      bipolar depression and mania. For the treatment of acute mania, a dose of 600 to
      800 mg/day is recommended. There has been concern of potential induction or
      worsening of hypomanic or manic symptoms at low doses via the ratio of 5HT2A/D2
      receptor antagonism, which at lower doses favors greater 5HT2A receptor blockade
      and thus increases dopamine concentrations. This article describes a case report
      of hypomania worsening to mania with psychotic features in a drug-naive patient
      who was started on low-dose quetiapine. This case adds to the existing literature
      of case reports indicating that low-dose quetiapine may be associated with
      induction or worsening of hypomanic/manic symptoms, while acknowledging the
      difficulty of suggesting a causal relationship. 

PMID- 25567838
TI  - Re: a predictive equation to guide vitamin D replacement dose in patients.

PMID- 25567839
TI  - Re: promotion of family-centered birth with gentle cesarean delivery.

PMID- 25567840
TI  - Re: family physicians' knowledge of commonly overused treatments and tests.

PMID- 25567843
TI  - Editorial: evolutionary medicine special issue.

PMID- 25567842
TI  - Editorial: 2008 year in review.

PMID- 25567841
TI  - Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio
      Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults.
AB  - BACKGROUND: Inactivated polio vaccine (IPV) is necessary for global polio
      eradication because oral polio vaccine can rarely cause poliomyelitis as it
      mutates and may fail to provide adequate immunity in immunocompromised
      populations. However, IPV is unaffordable for many developing countries.
      Intradermal IPV shows promise as a means to decrease the effective dose and cost
      of IPV, but prior studies, all using 20% of the standard dose used in
      intramuscular IPV, resulted in inferior antibody titers. METHODS: We randomly
      assigned 231 adults with well-controlled human immunodeficiency virus infection
      at a ratio of 2:2:2:1 to receive 40% of the standard dose of IPV intradermally,
      20% of the standard dose intradermally, the full standard dose intramuscularly,
      or 40% of the standard dose intramuscularly. Intradermal vaccination was done
      using the NanoPass MicronJet600 microneedle device. RESULTS: Baseline immunity
      was 87%, 90%, and 66% against poliovirus serotypes 1, 2, and 3, respectively.
      After vaccination, antibody titers increased a median of 64-fold. Vaccine
      response to 40% of the standard dose administered intradermally was comparable to
      that of the standard dose of IPV administered intramuscularly and resulted in
      higher (although not significantly) antibody titers. Intradermal administration
      had higher a incidence of local side effects (redness and itching) but a similar
      incidence of systemic side effects and was preferred by study participants over
      intramuscular administration. CONCLUSIONS: A 60% reduction in the standard IPV
      dose without reduction in antibody titers is possible through intradermal
      administration.

PMID- 25567844
TI  - Coinfection rates in Phi6 bacteriophage are enhanced by virus-induced changes in
      host cells.
AB  - Two or more viruses infecting the same host cell can interact in ways that
      profoundly affect disease dynamics and control, yet the factors determining
      coinfection rates are incompletely understood. Previous studies have focused on
      the mechanisms that viruses use to suppress coinfection, but recently the
      phenomenon of enhanced coinfection has also been documented. In the experiments
      described here, we explore the hypothesis that enhanced coinfection rates in the
      bacteriophage Phi6 are achieved by virus-induced upregulation of the Phi6
      receptor, which is the bacterial pilus. First, we confirmed that coinfection
      enhancement in Phi6 is virus-mediated by showing that Phi6 attaches significantly
      faster to infected cells than to uninfected cells. Second, we explored the
      hypothesis that coinfection enhancement in Phi6 depends upon changes in the
      expression of an inducible receptor. Consistent with this hypothesis, the closely
      related phage, Phi12, that uses constitutively expressed lipopolysaccharide as
      its receptor, attaches to infected and uninfected cells at the same rate. Our
      results, along with the previous finding that coinfection in Phi6 is limited to
      two virions, suggest that viruses may closely regulate rates of coinfection
      through mechanisms for both coinfection enhancement and exclusion. 

PMID- 25567845
TI  - Evolutionary ecology of microbial wars: within-host competition and (incidental)
      virulence.
AB  - Invading an occupied niche is a formidable ecological challenge, and one of
      particular human importance in the context of food-borne microbial pathogens. We
      discuss distinct categories of invader-triggered environmental change that
      facilitate invasion by emptying their niche of competitors. Evidence is reviewed
      that gut bacteria use such strategies to manipulate their environment (via
      bacteriocins, temperate phage viruses or immuno-manipulation) at the expense of
      their competitors are reviewed. The possible virulence implications of microbial
      warfare among multiple co-infecting strains are diverse. Killing competitors can
      reduce virulence by reducing overall microbial densities, or increase virulence
      if for example the allelopathic mechanism involves immuno-manipulation. Finally,
      we place microbial anti-competitor strategies in a social evolution framework,
      highlighting how costly anti-competitor strategies can be understood as examples
      of microbial spite. We conclude by discussing other invasive species that have
      also developed such proactive strategies of invasion. 

PMID- 25567846
TI  - Evolutionary biology and the avoidance of antimicrobial resistance.
AB  - Evolutionary biologists have largely left the search for solutions to the drug
      resistance crisis to biomedical scientists, physicians, veterinarians and public
      health specialists. We believe this is because the vast majority of professional
      evolutionary biologists consider the evolutionary science of drug resistance to
      be conceptually uninteresting. Using malaria as case study, we argue that it is
      not. We review examples of evolutionary thinking that challenge various fallacies
      dominating antimalarial therapy, and discuss open problems that need evolutionary
      insight. These problems are unlikely to be resolved by biomedical scientists
      ungrounded in evolutionary biology. Involvement by evolutionary biologists in the
      science of drug resistance requires no intellectual compromises: the problems are
      as conceptually challenging as they are important. 

PMID- 25567847
TI  - Cancer research meets evolutionary biology.
AB  - There is increasing evidence that Darwin's theory of evolution by natural
      selection provides insights into the etiology and treatment of cancer. On a
      microscopic scale, neoplastic cells meet the conditions for evolution by
      Darwinian selection: cell reproduction with heritable variability that affects
      cell survival and replication. This suggests that, like other areas of biological
      and biomedical research, Darwinian theory can provide a general framework for
      understanding many aspects of cancer, including problems of great clinical
      importance. With the availability of raw molecular data increasing rapidly, this
      theory may provide guidance in translating data into understanding and progress.
      Several conceptual and analytical tools from evolutionary biology can be applied
      to cancer biology. Two clinical problems may benefit most from the application of
      Darwinian theory: neoplastic progression and acquired therapeutic resistance. The
      Darwinian theory of cancer has especially profound implications for drug
      development, both in terms of explaining past difficulties, and pointing the way
      toward new approaches. Because cancer involves complex evolutionary processes,
      research should incorporate both tractable (simplified) experimental systems, and
      also longitudinal observational studies of the evolutionary dynamics of cancer in
      laboratory animals and in human patients. Cancer biology will require new tools
      to control the evolution of neoplastic cells. 

PMID- 25567848
TI  - Evolutionary genetics as a tool to target genes involved in phenotypes of medical
      relevance.
AB  - There is an increasing interest in detecting genes, or genomic regions, that have
      been targeted by natural selection. Indeed, the evolutionary approach for
      inferring the action of natural selection in the human genome represents a
      powerful tool for predicting regions of the genome potentially associated with
      disease and of interest in epidemiological genetic studies. Here, we review
      several examples going from candidate gene studies associated with specific
      phenotypes, including nutrition, infectious disease and climate adaptation, to
      whole genome scans for natural selection. All these studies illustrate the power
      of the evolutionary approach in identifying regions of the genome having played a
      major role in human survival and adaptation. 

PMID- 25567850
TI  - Heart disease is common in humans and chimpanzees, but is caused by different
      pathological processes.
AB  - Heart disease is common in both humans and chimpanzees, manifesting typically as
      sudden cardiac arrest or progressive heart failure. Surprisingly, although
      chimpanzees are our closest evolutionary relatives, the major cause of heart
      disease is different in the two species. Histopathology data of affected
      chimpanzee hearts from two primate centers, and analysis of literature indicate
      that sudden death in chimpanzees (and in gorillas and orangutans) is commonly
      associated with diffuse interstitial myocardial fibrosis of unknown cause. In
      contrast, most human heart disease results from coronary artery atherosclerosis,
      which occludes myocardial blood supply, causing ischemic damage. The typical
      myocardial infarction of humans due to coronary artery thrombosis is rare in
      these apes, despite their human-like coronary-risk-prone blood lipid profiles.
      Instead, chimpanzee 'heart attacks' are likely due to arrythmias triggered by
      myocardial fibrosis. Why do humans not often suffer from the fibrotic heart
      disease so common in our closest evolutionary cousins? Conversely, why do
      chimpanzees not have the kind of heart disease so common in humans? The answers
      could be of value to medical care, as well as to understanding human evolution. A
      preliminary attempt is made to explore possibilities at the histological level,
      with a focus on glycosylation changes. 

PMID- 25567851
TI  - Principles of ecological immunology.
AB  - Defending self against nonself is a major problem in a world in which individuals
      are under constant pressure from parasites that gain fitness benefits at a cost
      to their host. Defences that have evolved are diverse, and range from behavioural
      adaptations to physiochemical barriers. The immune defence is a final line of
      protection and is therefore of great importance. Given this importance,
      variability in immune defence would seem counterintuitive, yet that is what is
      observed. Ecological immunology attempts to explain this variation by invoking
      costs and trade-offs, and in turn proposing that the optimal immune defence will
      vary over environments. Studies in this field have been highly successful in
      establishing an evolutionary ecology framework around immunology. However, in
      order enrich our understanding of this area, it is perhaps time to broaden the
      focus to include parasites as more than simply elicitors of immune responses. In
      essence, to view immunity as produced by the host, the environment, and the
      active involvement of parasites. 

PMID- 25567852
TI  - Why do adaptive immune responses cross-react?
AB  - Antigen specificity of adaptive immune responses is often in the host's best
      interests, but with important and as yet unpredictable exceptions. For example,
      antibodies that bind to multiple flaviviral or malarial species can provide hosts
      with simultaneous protection against many parasite genotypes. Vaccinology often
      aims to harness such imprecision, because cross-reactive antibodies might provide
      broad-spectrum protection in the face of antigenic variation by parasites.
      However, the causes of cross-reactivity among immune responses are not always
      known, and here, we explore potential proximate and evolutionary explanations for
      cross-reactivity. We particularly consider whether cross-reactivity is the result
      of constraints on the ability of the immune system to process information about
      the world of antigens, or whether an intermediate level of cross-reactivity may
      instead represent an evolutionary optimum. We conclude with a series of open
      questions for future interdisciplinary research, including the suggestion that
      the evolutionary ecology of information processing might benefit from close
      examination of immunological data. 

PMID- 25567853
TI  - Infection and inflammation in somatic maintenance, growth and longevity.
AB  - All organisms must display a certain degree of environmental adaptability to
      survive and reproduce. Growth and reproduction are metabolically expensive and
      carry other costs that contribute to aging. Therefore, animals have developed
      physiologic strategies to assess the harshness of the environment before devoting
      resources to reproduction. Presumably, these strategies maximize the possibility
      for offspring survival. Current views of aging reflect a trade-off between
      reproductive fitness and somatic maintenance whereby environmental stress induces
      an adaptive metabolic response aimed at preserving cellular integrity while
      inhibiting growth, whereas favorable environmental conditions (abundance of food
      and water, and optimal temperature, etc.) promote growth and reproductive
      maturity but simultaneously increase cellular damage and aging. Here we propose
      that the prevalence of infectious pathogens in a given niche represents an
      additional environmental factor that, via innate immune pathways, actively shifts
      this balance in favor of somatic maintenance at the expense of reproduction and
      growth. We additionally propose the construction of a genetic model system with
      which to test this hypothesis. 

PMID- 25567849
TI  - Genomic sister-disorders of neurodevelopment: an evolutionary approach.
AB  - Genomic sister-disorders are defined here as diseases mediated by duplications
      versus deletions of the same region. Such disorders can provide unique
      information concerning the genomic underpinnings of human neurodevelopment
      because effects of diametric variation in gene copy number on cognitive and
      behavioral phenotypes can be inferred. We describe evidence from the literature
      on deletions versus duplications for the regions underlying the best-known human
      neurogenetic sister-disorders, including Williams syndrome, Velocardiofacial
      syndrome, and Smith-Magenis syndrome, as well as the X-chromosomal conditions
      Klinefelter and Turner syndromes. These data suggest that diametric copy-number
      alterations can, like diametric alterations to imprinted genes, generate
      contrasting phenotypes associated with autistic-spectrum and psychotic-spectrum
      conditions. Genomically based perturbations to the development of the human
      social brain are thus apparently mediated to a notable degree by effects of
      variation in gene copy number. We also conducted the first analyses of positive
      selection for genes in the regions affected by these disorders. We found evidence
      consistent with adaptive evolution of protein-coding genes, or selective sweeps,
      for three of the four sets of sister-syndromes analyzed. These studies of
      selection facilitate identification of candidate genes for the phenotypes
      observed and lend a novel evolutionary dimension to the analysis of human
      cognitive architecture and neurogenetic disorders. 

PMID- 25567855
TI  - Laparoscopic posterior mesh rectopexy for rectal prolapse is a safe procedure in
      older patients: A prospective follow-up study.
AB  - BACKGROUND AND AIMS: The aim of this study is to examine the clinical and
      functional outcome of laparoscopic posterior rectopexy in a consecutive series of
      adult patients with full-thickness rectal prolapse. MATERIAL AND METHODS:
      Preoperative data on demography, life-style practices, medication, comorbidity,
      and previous surgery for rectal prolapse were ascertained from patient charts.
      Information on operative procedure, and pre- and postoperative complications were
      recorded. Short- and long-term follow-up were done after a median of 60 days and
      2 years after surgery. RESULTS: Between 1 February 2009 to 1 June 2012, 81
      laparoscopic posterior rectopexies were done. Male-to-female ratio was 4:77,
      median age 73 [57-80.5] years and median ASA Grade 2. Conversion to open surgery
      was done in 6.2%, the median operating time was 82 min [66 - 102] and median
      length of hospital stay was 2 days [2-5.7]. Minor and major complications were
      seen in 5.3% and 14.8%, respectively. The 30-day mortality rate was 1.2%.
      Constipation or incontinence improved or disappeared in 65.2% and 74.4%,
      respectively. The cumulated recurrence rate was 11.1% after a median observation
      time of 2 years. CONCLUSION: Laparoscopic posterior rectopexy is a safe and well
      tolerated procedure in older patients and can be done with acceptable
      complications and recurrence rates and short hospital stays. Laparoscopic
      posterior rectopexy seems to improve bowel function in many patients.

PMID- 25567854
TI  - Percutaneous cholecystostomy is an effective definitive treatment option for
      acute acalculous cholecystitis.
AB  - AIMS: Acute acalculous cholecystitis can be treated with percutaneous
      cholecystostomy in critically ill patients unfit for surgery. However, the
      evidence on the outcome is sparse. We conducted a retrospective analysis of acute
      acalculous cholecystitis patients treated with percutaneous cholecystostomy
      during a 10-year study period. METHODS: An observational study of 56 consecutive
      patients treated with percutaneous cholecystostomy for acute acalculous
      cholecystitis was conducted in the period from 1 June 2002 to 31 May 2012. All
      data were obtained by review of medical records. RESULTS: A total of 56
      consecutive patients were treated with percutaneous cholecystostomy for acute
      acalculous cholecystitis. Six patients (10.7%) died within 30 days after the
      procedure. Percutaneous cholecystostomy could serve as a definitive treatment
      option in 45 patients (80.4%), whereas 1 patient (1.8%) required cholecystectomy
      due to recurrence of cholecystitis. Four patients (7.1%) were treated with
      percutaneous cholecystostomy as a bridging procedure to subsequent elective
      laparoscopic cholecystectomy within a median of 8.8 months (range: 7.7-33.4
      months). There was no significant difference in the risk of cholecystitis
      recurrence between patients with (6/37) and without (2/3) contrast passage to the
      duodenum on cholangiography (p = 0.096). CONCLUSION: Percutaneous cholecystostomy
      is successful as a definitive treatment option in the majority of patients with
      acute acalculous cholecystitis. It is associated with a low rate of mortality and
      subsequent cholecystectomy.

PMID- 25567856
TI  - Surgical complications following 1670 consecutive adult renal transplantations: A
      single center study.
AB  - BACKGROUND AND AIMS: The aim of the study was to clarify the frequency and the
      sequel of surgical complications occurring within 1 year after renal
      transplantation. PATIENTS AND METHODS: Surgical complications after 1670
      consecutive adult kidney transplantations performed between 2000 and 2009 were
      retrospectively analyzed. In 2%, a living-related allograft was used, and 10%
      were retransplantations. An intravesical technique without stenting was used for
      the ureteric implantation. RESULTS: There were 282 surgical complications
      occurring in 259 (15.5%) transplantations. Ureteral obstruction occurred in 53
      (3.1%), lymphoceles in 39 (1.5%), postoperative hemorrhage in 36 (2.1%), and
      renal vein thrombosis in 22 (1.3%) patients, respectively. Out of the 17 lung
      emboli, 4 were fatal. Male recipients had twice as much ureteral stenosis as
      female (2.4 vs 1.2%, p < 0.05), and the opposite was true of urinary leakage
      (1.8% vs 4.0%, p < 0.025). Five-year patient and graft survival was impaired in
      patients with complications compared with patients without complications. Five
      year patient survival was 92% versus 88% and graft survival 87% versus 74%.
      CONCLUSION: Surgical complications impair patient and graft survival after kidney
      transplantation.

PMID- 25567857
TI  - Gene-drive in age-structured insect populations.
AB  - To date, models of gene-drive mechanisms proposed for replacing wild-type
      mosquitoes with transgenic strains that cannot transmit diseases have assumed no
      age or mating structure. We developed a more detailed model to analyze the
      effects of age and mating-related factors on the number of engineered insects
      that must be introduced into a wild population to achieve successful gene-drive
      based on the Medea and engineered underdominance mechanisms. We found that models
      without age-structure and mating details can substantially overestimate or
      underestimate the numbers of engineered insects that must be introduced. In
      general, introduction thresholds are lowest when young adults are introduced.
      When both males and females are introduced, assortative mating by age has little
      impact on the introduction threshold unless the introduced females have
      diminished reproductive ability because of their age. However, when only males
      are introduced, assortative mating by age is generally predicted to increase
      introduction thresholds. In most cases, introduction thresholds are much higher
      for male-only introductions than for both-sex introductions, but when mating is
      nearly random and the introduced insects are adults with Medea constructs, male
      only introductions can have somewhat lower thresholds than both-sex
      introductions. Results from this model suggest specific parameters that should be
      measured in field experiments. 

PMID- 25567858
TI  - A metapopulation model for the introgression from genetically modified plants
      into their wild relatives.
AB  - Most models on introgression from genetically modified (GM) plants have focused
      on small spatial scales, modelling gene flow from a field containing GM plants
      into a single adjacent population of a wild relative. Here, we present a model to
      study the effect of introgression from multiple plantations into the whole
      metapopulation of the wild relative. The most important result of the model is
      that even very low levels of introgression and selection can lead to a high
      probability that the transgene goes to fixation in the metapopulation.
      Furthermore, the overall frequency of the transgene in the metapopulation, after
      a certain number of generations of introgression, depends on the population
      dynamics. If there is a high rate of migration or a high rate of population
      turnover, the overall transgene frequency is much higher than with lower rates.
      However, under an island model of population structure, this increased frequency
      has only a very small effect on the probability of fixation of the transgene.
      Considering these results, studies on the potential ecological risks of
      introgression from GM plants should look not only at the rate of introgression
      and selection acting on the transgene, but also at the metapopulation dynamics of
      the wild relative. 

PMID- 25567859
TI  - Rapid evolution in crop-weed hybrids under artificial selection for divergent
      life histories.
AB  - When species hybridize, offspring typically exhibit reduced fitness and
      maladapted phenotypes. This situation has biosafety implications regarding the
      unintended spread of novel transgenes, and risk assessments of crop-wild hybrids
      often assume that poorly adapted hybrid progeny will not evolve adaptive
      phenotypes. We explored the evolutionary potential of early generation hybrids
      using nontransgenic wild and cultivated radish (Raphanus raphanistrum, Raphanus
      sativus) as a model system. We imposed four generations of selection for two
      weedy traits - early flowering or large size - and measured responses in a common
      garden in Michigan, USA. Under selection for early flowering, hybrids evolved to
      flower as early as wild lineages, which changed little. These early-flowering
      hybrids also recovered wild-type pollen fertility, suggesting a genetic
      correlation that could accelerate the loss of crop traits when a short life cycle
      is advantageous. Under selection for large size at reproduction, hybrids evolved
      longer leaves faster than wild lineages, a potentially advantageous phenotype
      under longer growing seasons. Although early generation hybrid offspring have
      reduced fitness, our findings provide novel support for rapid adaptation in crop
      wild hybrid populations. Biosafety risk assessment programs should consider the
      possibility of rapid evolution of weedy traits from early generations of
      seemingly unfit crop-wild hybrids. 

PMID- 25567860
TI  - Common garden comparisons of native and introduced plant populations: latitudinal
      clines can obscure evolutionary inferences.
AB  - Common garden studies are increasingly used to identify differences in phenotypic
      traits between native and introduced genotypes, often ignoring sources of among
      population variation within each range. We re-analyzed data from 32 common garden
      studies of 28 plant species that tested for rapid evolution associated with
      biological invasion. Our goals were: (i) to identify patterns of phenotypic trait
      variation among populations within native and introduced ranges, and (ii) to
      explore the consequences of this variation for how differences between the ranges
      are interpreted. We combined life history and physiologic traits into a single
      principal component (PCALL) and also compared subsets of traits related to size,
      reproduction, and defense (PCSIZE, PCREP, and PCDEF, respectively). On average,
      introduced populations exhibited increased growth and reproduction compared to
      native conspecifics when latitude was not included in statistical models.
      However, significant correlations between PC-scores and latitude were detected in
      both the native and introduced ranges, indicating population differentiation
      along latitudinal gradients. When latitude was explicitly incorporated into
      statistical models as a covariate, it reduced the magnitude and reversed the
      direction of the effect for PCALL and PCSIZE. These results indicate that
      unrecognized geographic clines in phenotypic traits can confound inferences about
      the causes of evolutionary change in invasive plants. 

PMID- 25567861
TI  - Fishery-induced selection on an Alpine whitefish: quantifying genetic and
      environmental effects on individual growth rate.
AB  - Size-selective fishing, environmental changes and reproductive strategies are
      expected to affect life-history traits such as the individual growth rate. The
      relative contribution of these factors is not clear, particularly whether size
      selective fishing can have a substantial impact on the genetics and hence on the
      evolution of individual growth rates in wild populations. We analysed a 25-year
      monitoring survey of an isolated population of the Alpine whitefish Coregonus
      palaea. We determined the selection differentials on growth rate, the actual
      change of growth rate over time and indicators of reproductive strategies that
      may potentially change over time. The selection differential can be reliably
      estimated in our study population because almost all the fish are harvested
      within their first years of life, i.e. few fish escape fishing mortality. We
      found a marked decline in average adult growth rate over the 25 years and a
      significant selection differential for adult growth, but no evidence for any
      linear change in reproductive strategies over time. Assuming that the
      heritability of growth in this whitefish corresponds to what was found in other
      salmonids, about a third of the observed decline in growth rate would be linked
      to fishery-induced evolution. Size-selective fishing seems to affect
      substantially the genetics of individual growth in our study population. 

PMID- 25567862
TI  - Mixed infections and the competitive fitness of faster-acting genetically
      modified viruses.
AB  - Faster-acting recombinant baculoviruses have shown potential for improved
      suppression of insect pests, but their ecological impact on target and nontarget
      hosts and naturally occurring pathogens needs to be assessed. Previous studies
      have focused on the fitness of recombinants at the between-hosts level. However,
      the population structure of the transmission stages will also be decided by
      within-host selection. Here we have experimentally quantified the within-host
      competitive fitness of a fast-acting recombinant Autographa californica
      multicapsid nucleopolyhedrovirus missing the endogenous egt gene (vEGTDEL), by
      means of direct competition in single- and serial-passage experiments with its
      parental virus. Quantitative real-time PCR was employed to determine the ratio of
      these two viruses in passaged mixtures. We found that vEGTDEL had reduced within
      host fitness: per passage the ratio of wild type to vEGTDEL was on average
      enhanced by a factor of 1.53 (single passage) and 1.68 (serial passage). There is
      also frequency-dependence: the higher the frequency of vEGTDEL, the stronger the
      selection against it is. Additionally, the virus ratio is a predictor of time to
      host death and virus yield. Our results show that egt is important to within-host
      fitness and allow for a more complete assessment of the ecological impact of
      recombinant baculovirus release. 

PMID- 25567863
TI  - Genetic diversity and divergence among coastal and offshore reefs in a hard coral
      depend on geographic discontinuity and oceanic currents.
AB  - Understanding the evolutionary processes that have shaped existing patterns of
      genetic diversity of reef-building corals over broad scales is required to inform
      long-term conservation planning. Genetic structure and diversity of the mass
      spawning hard coral, Acropora tenuis, were assessed with seven DNA microsatellite
      loci from a series of isolated and discontinuous coastal and offshore reef
      systems in northwest Australia. Significant subdivision was detected among all
      sites (F ST = 0.062, R ST = 0.090), with the majority of this variation due to
      genetic differentiation among reef systems. In addition, genetic divergence was
      detected between the coastal and offshore zones that cannot be adequately
      explained by geographic distance, indicating that transport of larvae between
      these zones via large-scale oceanic currents is rare even over time frames that
      account for connectivity over multiple generations. Significant differences in
      the amount of genetic diversity at each system were also detected, with higher
      diversity observed on the lower latitude reefs. The implications are that these
      reef systems of northwest Australia are not only demographically independent, but
      that they will also have to rely on their own genetic diversity to adapt to
      environmental change over the next few decades to centuries. 

PMID- 25567864
TI  - Estimating fisheries-induced selection: traditional gear selectivity research
      meets fisheries-induced evolution.
AB  - The study of fisheries-induced evolution is a research field which is becoming
      recognized both as an important and interesting problem in applied evolution, as
      well as a practical management problem in fisheries. Much of the research in
      fisheries-induced evolution has focussed on quantifying and proving that an
      evolutionary response has taken place, but less effort has been invested on the
      actual processes and traits underlying capture of a fish by a fishing gear. This
      knowledge is not only needed to understand possible phenotypic selection
      associated to fishing but also to help to device sustainable fisheries and
      management strategies. Here, we draw attention to the existing knowledge about
      selectivity of fishing gears and outline the ways in which this information could
      be utilized in the context of fisheries-induced evolution. To these ends, we will
      introduce a mathematical framework commonly applied to quantify fishing gear
      selectivity, illustrate the link between gear selectivity and the change in the
      distribution of phenotypes induced by fishing, review what is known about
      selectivity of commonly used fishing gears, and discuss how this knowledge could
      be applied to improve attempts to predict evolutionary impacts of fishing. 

PMID- 25567865
TI  - [Recent progress in single-cell RNA-Seq analysis].
AB  - Cell heterogeneity is a general feature of biological tissues. Standard
      transcriptome analysis approaches require tens of thousands of cells to provide
      an average view of gene expression and ignore the information of gene expression
      heterogeneity. The single-cell RNA-Seq technologies profile gene expression at
      the single-cell level and serve as powerful tools to identify distinct phenotypic
      cell types within a heterogeneous population. The single-cell RNA-Seq
      technologies have been developed rapidly in recent years. The methodological
      progress includes a variety of cDNA amplification methods, the quantitative
      analysis of the sensitivity and noise of the technologies, and the development of
      the low-coverage high-throughput single-cell RNA-Seq and the in situ RNA-Seq
      technologies. Furthermore, the scope of application is extended from early
      embryonic development to tissue and organ development, immunology and oncology.
      In this review, we discuss recent progress in methodology and applications of the
      single-cell RNA-Seq technologies. 

PMID- 25567866
TI  - [The application of exome sequencing in human disease].
AB  - It is estimated that approximately 85% of human disease mutations are located in
      protein coding regions, therefore selectively sequencing all protein coding
      regions (exome) would be cost-effective and an alternative strategy to identify
      diseases' varaints. In 2009, scientists successfully identified one missense
      mutation in MYH3 among 4 individuals with Freeman Sheldon syndrome (one autosomal
      dominant disease) through exome sequencing. Since then, exome sequencing has been
      widely used to identify disease causative or susceptibility genes in Mendelian
      disorders and complex diseases. The application of exome sequencing in human
      diseases were summarized in this review.

PMID- 25567867
TI  - [Whole-genome sequencing and its application in the research and diagnoses of
      genetic diseases].
AB  - Recently, with the decreasing cost of DNA sequencing and improving strategy of
      data analysis, whole-genome sequencing (WGS) has been used for detection of
      pathogenic genes in cancer, Mendelian diseases and other complex diseases and
      gradually become applicable for clinical diagnosis. WGS enables not only the
      identification of single nucleotide variants (SNVs), insertions and deletions
      (InDels) both in coding region and non-coding regions, but also the detection of
      copy number variations (CNVs) and structural variations (SVs) on a genome scale.
      In this review, we discuss the canonical workflow and methods of bioinformatics
      analysis in WGS, and its application in disease research and clinical diagnosis.
      In addition, this review provides an overview in application, progress and
      challenge on WGS in medical genetics. 

PMID- 25567868
TI  - [Strategies of genome-wide association study based on high-throughput
      sequencing].
AB  - Genome-wide association studies (GWASs) have been playing an important role on
      human complex diseases. Generally speaking, GWAS tries to detect the relationship
      between genome-wide genetic variants and measurable traits in the population
      level. Although fruitful, array-based GWASs still exist some problems, for
      example, the so-called missing heritability--significantly associated SNPs can
      only explain a small part of phenotypic variation. Other problems include that,
      in some traits, significantly associated SNPs in one study are hard to be
      repeated by other studies; and that the functions of significantly associated
      SNPs are often difficult to interpret. High-throughput sequencing, also known as
      next-generation sequencing (NGS), could be one of the most promising technologies
      to solve those problems by quickly producing accurate variations in a high
      throughput way. NGS-based GWASs (NGS-GWAS), to some extent, provide a better
      solution compared with traditional array-based GWASs. We systematically review
      the strategies and methods for NGS-GWASs, pick out the most feasible and
      efficient strategies and methods for NGS-GWASs, and discuss their applications in
      personalized medicine. 

PMID- 25567869
TI  - [Application of next generation sequencing in gene identification and genetic
      diagnosis of hereditary hearing loss].
AB  - More than 50% cases with hearing loss are caused by genetic defects. With the
      development of genomics technology, molecular genetics of hearing loss has become
      a cutting-edge field under investigation in otology. The next generation
      sequencing has provided a new model originated from sequencing data to genetic
      disease study, and has made a revolutionary change in the strategy of gene
      identification for genetic diseases. Due to the application of next generation
      sequencing technology, gene identification of hearing loss has been accelerated
      in recent years, and moreover, the new technology and strategy were explored to
      clinical application. In this review, we briefly introduce the current situation
      of hereditary hearing loss research, and the application and perspective of next
      generation sequencing in this field. 

PMID- 25567870
TI  - [Sequencing technology in gene diagnosis and its application].
AB  - The study of gene mutation is one of the hot topics in the field of life science
      nowadays, and the related detection methods and diagnostic technology have been
      developed rapidly. Sequencing technology plays an indispensable role in the
      definite diagnosis and classification of genetic diseases. In this review, we
      summarize the research progress in sequencing technology, evaluate the advantages
      and disadvantages of 1(st) ~3(rd) generation of sequencing technology, and
      describe its application in gene diagnosis. Also we made forecasts and prospects
      on its development trend. 

PMID- 25567872
TI  - [Advances in repeat-primed PCR assay for the genetic diagnosis of dynamic
      mutation diseases with large pathogenic expansions].
AB  - Dynamic mutation diseases are genetic diseases caused by unstable repeat
      expansions in coding region or noncoding region. The unstable repeat expansions
      located in the noncoding region usually perform as large expansions which the
      standard PCR assay is difficult to amplify. Traditional detection methods,
      including Southern blot, are supposed to be time-consuming and labor-wasting. A
      new method called fluorescent repeat-primed PCR assay was brought into genetic
      diagnosis. Here, we reviewed the advances in repeat-primed PCR assay for the
      genetic diagnoses of myotonic dystrophy, Friedreich's ataxia, SCA10, and
      amyotrophic lateral sclerosis or frontotemporal dementia caused by C9 or f72
      mutations.

PMID- 25567871
TI  - [Progress in the study of syndromic hearing loss resulted from neural crest
      abnormalities].
AB  - More than 400 types of syndromic hearing loss (SHL) have been reported so far, in
      which Waardenburg syndrome (WS), congenital microtia syndrome (CMS), and large
      vestibular aqueduct syndrome (LVAS) are the most common ones in clinic. However,
      it is difficult to study the genetic basis and pathogenesis of SHL in a
      systematical way because of the strong clinical and genetic heterogeneity of SHL.
      Dysfunction of neural crest cells (NCC), which are caused by the gene interaction
      network extended from SOX10 and PAX3, are relevant to the phenotype of WS, CMS
      and LVAS. Our previous study also confirmed that the gene network was involved in
      the pathogenesis of WS. In this review, we summarize research progress in the
      pathogenic mechanisms of SHL resulted from defects in neural crest decelopment,
      and provide the gene interaction network of neural crest abnormalities resulting
      in SHL, and hope to provide research ideas and theoretical basis for the
      systematical study on pathogenesis of common SHL. 

PMID- 25567874
TI  - [Mitochondrial genome analysis in the probands of six Chinese families with
      MELAS].
AB  - Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)
      is a genetically heterogeneous disorder. The most prevalent mitochondrial DNA
      (mtDNA) mutation associated with MELAS is the m.3243A>G transition in the
      mitochondrial tRNA(Leu(UUR)) gene. Here, we report the clinical, genetic and
      molecular characterization of six probands from Han Chinese families with MELAS.
      Four of six probands carried the heteroplasmic m.3243A>G mutation. The levels of
      mutation load ranged from 29% to 59%, which were correlated with the severity of
      the clinical phenotypes. Two probands with MELAS/Leigh overlap were 3243 A>G
      negative, whose severity and relapse were greater than the other 4 probands. One
      proband with MELAS/Leigh harbored the known ND5 m.13094T>C mutation, which is
      related to MELAS/Leigh overlap and cerebella ataxia. Sequence analysis of entire
      mtDNA showed the distinct sets of variants including some variants that may be
      associated with diabetes, hearing loss, seizures, cardiomyopathy, and Leigh
      syndrome. Our data suggested that the phenotype and severity of MELAS mainly
      depend on the mutation load, and some variants may partially contribute to the
      phenotype and diversity. Our finding also highlighted the complexity of the
      relationship between genotype and phenotype in MELAS. 

PMID- 25567873
TI  - [Mutation analysis of the pathogenic gene in a Chinese family with hereditary
      hemochromatosis].
AB  - Hereditary hemochromatosis (HHC) is a rare autosomal recessive disorder. We
      recruited a consanguineous Chinese family including the proband with HHC and
      other four members without HHC. Using whole-exome sequencing, we identified two
      homozygous mutations (c.G18C [p.Q6H] and c.GC962_963AA [p.C321X]) in the
      hemojuvelin gene (HJV) in the proband with HHC. No mutation was found in other
      four previously identified HHC related genes, HAMP, TFR2, FPN and HFE. The
      functional impact of p.Q6H mutation is weak whereas p.C321X, a premature
      termination mutation, results in a truncated HJV protein, which lacks the
      glycosylphosphatidylinositol (GPI) anchor domain. In addition to the mutations in
      HJV, other 12 homozygous mutations were identified in this patient. However, none
      of these mutations showed strong damaging impact and the mutated genes are not
      related to iron metabolism. Our in-house data further demonstrated that p.C321X
      is absent in the general Chinese population, suggesting that the homozygous
      mutation p.C321X in HJV is causative in the patient with HHC. Accordingly, all of
      the four members without HHC from the same family carried wild-type alleles or
      heterozygous mutations, but not the homozygous mutation in this site. Thus, we
      found for the first time that the homozygous mutation p.C321X in HJV can result
      in HHC, which will help genetic diagnosis and prenatal counseling for HHC. 

PMID- 25567875
TI  - [The construction of urine-derived cell lines from patients with spinal muscular
      atrophy].
AB  - Spinal muscular atrophy (SMA) is a common neurodegenerative disease in childhood
      and infancy, clinically characterized by progressive and symmetric muscular
      weakness and atrophy. Few effective therapies are available now, and SMA is one
      of the most common genetic causes of infantile mortality. SMA patient-derived
      cells are beneficial in basic research on this disease, but the most common model
      cell, fibroblasts can only be obtained through invasive procedures such as muscle
      or skin biopsy, which are unwelcome to patients and their families. In this
      study, fresh urine from SMA patients and healthy controls was collected and
      centrifuged, and the urine sediment was cultured in vitro. The growth
      characteristics of urine-derived cells were observed, and the survival of motor
      neuron (SMN) gene, and the amount and localization of SMN protein in different
      urine cell lines were investigated. In total, 25 urine cell lines from 11 SMA
      patients and 14 healthy controls were established. These urine-derived cells
      expand robustly in vitro with stable cell morphological characteristics. The
      urine cell lines derived from patients carry the SMN1 gene defect and express a
      low level of SMN protein, while the intracellular localization of SMN protein is
      normal. Urine-derived cell culture technology is simple, non-invasive and highly
      reproducible, a way of obtaining and storing rare cell samples from SMA patients
      with which to study the pathogenesis of SMA. 

PMID- 25567876
TI  - [In vivo electroporation of newborn mouse retina].
AB  - In vivo electroporation is the process referred to a transient increase in the
      permeability of cell membranes upon high electric field pulses and delivery of
      engineered constructs into cells. Compared with the viral-mediated gene transfer
      system, the in vivo electroporation technique has several advantages, such as
      safe, high efficiency, rapid, stable and wide application. Thus, this technique
      has been widely used in the studies of many tissues or organs, including the eye.
      Here, we report the application of in vivo electroporation in the newborn mouse
      retina. DNA plasmid of GFP expression vector with high concentration was directly
      injected into the subretinal space of neonatal mouse pups. The DNA was then
      transfected into the retinal cells after several pulses of high voltage.
      Transfected GFP allowed clear visualization of cell morphologies in cryo-sections
      and the GFP was highly expressed in retinal outer nuclear layer. The results
      showed that this technique can effectively transfer the genes into retinal cells.
      In vivo electroporation will be a useful tool for the study of retinal
      development and function. 

PMID- 25567877
TI  - Neuromuscular electrical stimulation for thromboprophylaxis: A systematic review.
AB  - OBJECTIVE: To evaluate the effect of neuromuscular electrical stimulation on
      lower limb venous blood flow and its role in thromboprophylaxis. METHOD:
      Systematic review of randomised and non-randomised studies evaluating
      neuromuscular electrical stimulation, and reporting one or more of the following
      outcomes: incidence of venous thromboembolism, venous blood flow and discomfort
      profile. RESULTS: Twenty-one articles were identified. Review of these articles
      showed that neuromuscular electrical stimulation increases venous blood flow and
      is generally associated with an acceptable tolerability, potentially leading to
      good patient compliance. Ten comparative studies reported DVT incidence, ranging
      from 2% to 50% with neuromuscular electrical stimulation and 6% to 47.1% in
      controls. There were significant differences, among included studies, in terms of
      patient population, neuromuscular electrical stimulation delivery, diagnosis of
      venous thromboembolism and blood flow measurements. CONCLUSION: Neuromuscular
      electrical stimulation increases venous blood flow and is well tolerated, but
      current evidence does not support a role for neuromuscular electrical stimulation
      in thromboprophylaxis. Randomised controlled trials are required to investigate
      the clinical utility of neuromuscular electrical stimulation in this setting.

PMID- 25567878
TI  - Toward Darwinian fisheries management.
AB  - There is increasing evidence that fishing may cause rapid contemporary evolution
      in freshwater and marine fish populations. This has led to growing concern about
      the possible consequences such evolutionary change might have for aquatic
      ecosystems and the utility of those ecosystems to society. This special issue
      contains contributions from a symposium on fisheries-induced evolution held at
      the American Fisheries Society Annual Meeting in August 2008. Contributions
      include primary studies and reviews of field-based and experimental evidence, and
      several theoretical modeling studies advancing life-history theory and
      investigating potential management options. In this introduction we review the
      state of research in the field, discuss current controversies, and identify
      contributions made by the papers in this issue to the knowledge of fisheries
      induced evolution. We end by suggesting directions for future research. 

PMID- 25567879
TI  - Life history change in commercially exploited fish stocks: an analysis of trends
      across studies.
AB  - Age and size at maturation have declined dramatically in many commercial fish
      stocks over the past few decades - changes that have been widely attributed to
      fishing pressure. We performed an analysis of such trends across multiple
      studies, to test for the consistency of life history changes under fishing, and
      for their association with the intensity of exploitation (fishing mortality
      rate). We analyzed 143 time series from 37 commercial fish stocks, the majority
      of which originated from the North Atlantic. Rates of phenotypic change were
      calculated for two traditional maturation indices (length and age at 50%
      maturity), as well as for probabilistic maturation reaction norms (PMRNs). We
      found that all three indices declined in heavily exploited populations, and at a
      rate that was strongly correlated with the intensity of fishing (for length at
      50% maturity and PMRNs). These results support previous assertions that fishing
      pressure is playing a major role in the life history changes observed in
      commercial fish stocks. Rates of change were as strong for PMRNs as for age and
      size at 50% maturity, which is consistent with the hypothesis that fishing
      induced phenotypic changes can sometimes have a genetic basis. 

PMID- 25567880
TI  - The role of experiments in understanding fishery-induced evolution.
AB  - Evidence of fishery-induced evolution has been accumulating rapidly from various
      avenues of investigation. Here we review the knowledge gained from experimental
      approaches. The strength of experiments is in their ability to disentangle
      genetic from environmental differences. Common garden experiments have provided
      direct evidence of adaptive divergence in the wild and therefore the evolvability
      of various traits that influence production in numerous species. Most of these
      cases involve countergradient variation in physiological, life history, and
      behavioral traits. Selection experiments have provided examples of rapid life
      history evolution and, more importantly, that fishery-induced selection pressures
      cause simultaneous divergence of not one but a cluster of genetically and
      phenotypically correlated traits that include physiology, behavior, reproduction,
      and other life history characters. The drawbacks of experiments are uncertainties
      in the scale-up from small, simple environments to larger and more complex
      systems; the concern that taxons with short life cycles used for experimental
      research are atypical of those of harvested species; and the difficulty of
      adequately simulating selection due to fishing. Despite these limitations,
      experiments have contributed greatly to our understanding of fishery-induced
      evolution on both empirical and theoretical levels. Future advances will depend
      on integrating knowledge from experiments with those from modeling, field
      studies, and molecular genetic approaches. 

PMID- 25567881
TI  - Comparison of demographic and direct methods to calculate probabilistic
      maturation reaction norms for Flemish Cap cod (Gadus morhua).
AB  - Age and length at maturation have declined in many fish populations and this has
      been hypothesized to be a genetic change caused by high fishing mortality.
      Probabilistic Maturation Reaction Norms (PMRNs) have been used as a tool to gain
      a better understanding of the possible genetic nature of these changes. The
      demographic and direct methods are two ways to calculate PMRNs. The data
      requirements are more often met for the demographic method than for the direct
      method which requires the identification of recruit spawners. However, the
      demographic method relies on more assumptions than the direct method, typically
      assuming equality of growth and mortality rates for immature and mature
      individuals within an age class. This study provides the first direct comparison
      of demographic and direct methods and shows that both methods produce comparable
      results. Differences between methods are hypothesized to be owed to possible
      differences in growth rate between mature and immature individuals in Flemish Cap
      cod. 

PMID- 25567882
TI  - Is fishing selective for physiological and energetic characteristics in migratory
      adult sockeye salmon?
AB  - There is extensive evidence that fishing is often selective for specific
      phenotypic characteristics, and that selective harvest can thus result in
      genotypic change. To date, however, there are no studies that evaluate whether
      fishing is selective for certain physiological or energetic characteristics that
      may influence fish behaviour and thus vulnerability to capture. Here, adult
      sockeye salmon (Oncorhynchus nerka) were used as a model to test the null
      hypothesis that fishing is not selective for specific physiological or energetic
      traits. Fish were intercepted during their spawning migrations, implanted with a
      gastric radio transmitter, and biopsied (i.e., non-lethally sampled for blood,
      gill tissue and quantification of energetic status). In both 2003 and 2006, we
      tagged and biopsied 301 and 770 sockeye salmon, respectively, in the marine
      environment en route to their natal river system to spawn. In 2006 an additional
      378 individuals were tagged and biopsied in freshwater. We found that 23 (7.6%)
      of the marine fish tagged in 2003, 78 (10.1%) of the marine fish tagged in 2006
      and 57 (15.1%) of the freshwater fish tagged in 2006 were harvested by one of
      three fisheries sectors that operate in the coastal marine environment and the
      Fraser River (i.e. commercial, recreational or First Nations fisheries between
      the site of release and Hell's Gate in the Fraser River, approximately 250 km
      upriver and 465 km from the ocean tagging site). However, fisheries were not open
      continually or consistently in different locations and for different fisheries
      sectors necessitating a paired analytical approach. As such, for statistical
      analyses we paired individual fish that were harvested with another fish of the
      same genetic stock that was released on the same date and exhibited similar
      migration behaviour, except that they successfully evaded capture and reached
      natal spawning grounds. Using two-tailed Wilcoxon matched pairs signed-rank
      tests, we revealed that the physiological and energetic characteristics of
      harvested fish did not differ from those of the successful migrants despite
      evaluating a number of biochemical (e.g. plasma metabolites, cortisol, plasma
      ions, gill Na(+)/K(+)-ATPase) and energetic (e.g. gross somatic energy density)
      variables (P's all >0.10). However, for some analyses we suffered low statistical
      power and the study design had several shortcomings that could have made
      detection of differences difficult. We suggest that additional research explore
      the concept of fishing-induced selection for physiological characteristics
      because physiology is closely linked to three traits where fisheries-induced
      selection does occur (i.e. life-history, behaviour and morphology). 

PMID- 25567883
TI  - Life-history traits and energetic status in relation to vulnerability to angling
      in an experimentally selected teleost fish.
AB  - In recreational fisheries, a correlation has been established between fishing
      induced selection pressures and the metabolic traits of individual fish. This
      study used a population of largemouth bass (Micropterus salmoides) with lines of
      low vulnerability fish (LVF) and high vulnerability fish (HVF) that were
      previously established through artificial truncation selection experiments. The
      main objective was to evaluate if differential vulnerability to angling was
      correlated with growth, energetics and nutritional condition during the sub-adult
      stage. Absolute growth rate was found to be between 9% and 17% higher for LVF
      compared with HVF over a 6-month period in three experimental ponds. The
      gonadosomatic index in females was lower for LVF compared with HVF in one
      experimental pond. No significant differences in energy stores (measured using
      body constituent analysis) were observed between LVF and HVF. In addition, both
      groups were consuming the same prey items as evidenced by stomach content
      analysis. The inherent reasons behind differential vulnerability to angling are
      complex, and selection for these opposing phenotypes appears to select for
      differing growth rates, although the driving factors remain unclear. These traits
      are important from a life-history perspective, and alterations to their frequency
      as a result of fishing-induced selection could alter fish population structure.
      These findings further emphasize the need to incorporate evolutionary principles
      into fisheries management activities. 

PMID- 25567884
TI  - Avoidance of fisheries-induced evolution: management implications for catch
      selectivity and limit reference points.
AB  - I examined how the fitness (r) associated with early- and late-maturing genotypes
      varies with fishing mortality (F) and age-/size-specific probability of capture.
      Life-history data on Newfoundland's northern Atlantic cod (Gadus morhua) allowed
      for the estimation of r for individuals maturing at 4 and 7 year in the absence
      of fishing. Catch selectivity data associated with four types of fishing gear
      (trap, gillnet, handline, otter trawl) were then incorporated to examine how r
      varied with gear type and with F. The resulting fitness functions were then used
      to estimate the F above which selection would favour early (4 year) rather than
      delayed (7 year) maturity. This evolutionarily-sensitive threshold, F evol,
      identifies a limit reference point somewhat similar to those used to define
      overfishing (e.g., F msy, F 0.1). Over-exploitation of northern cod resulted in
      fishing mortalities considerably greater than those required to effect
      evolutionary change. Selection for early maturity is reduced by the dome-shaped
      selectivities characteristic of fixed gears such as handlines (the greater the
      leptokurtosis, the lower the probability of a selection response) and enhanced by
      the knife-edged selectivities of bottom trawls. Strategies to minimize genetic
      change are consistent with traditional management objectives (e.g., yield
      maximization, population increase). Compliance with harvest control rules guided
      by evolutionarily-sensitive limit reference points, which may be achieved by
      adherence to traditional reference points such as F msy and F 0.1, should be
      sufficient to minimize the probability of fisheries-induced evolution for
      commercially exploited species. 

PMID- 25567885
TI  - Quantifying selection differentials caused by recreational fishing: development
      of modeling framework and application to reproductive investment in pike (Esox
      lucius).
AB  - Methods for quantifying selection pressures on adaptive traits affected by size
      selective fishing are still scarce, and none have as yet been developed for
      recreational fishing. We present an ecologically realistic age-structured model
      specifically tailored to recreational fishing that allows estimating selection
      differentials on adaptive life-history traits. The model accounts for multiple
      ecological feedbacks, which result in density-dependent and frequency-dependent
      selection. We study selection differentials on annual reproductive investment
      under size-selective exploitation in a highly demanded freshwater recreational
      fish species, northern pike (Esox lucius L.). We find that recreational angling
      mortality exerts positive selection differentials on annual reproductive
      investment, in agreement with predictions from life-history theory. The strength
      of selection increases with the intensity of harvesting. We also find that
      selection on reproductive investment can be reduced by implementing simple
      harvest regulations such as minimum-size limits. The general, yet computationally
      simple, methods introduced here allow evaluating and comparing selection
      pressures on adaptive traits in other fish populations and species, and thus have
      the potential to become a tool for evolutionary impact assessment of harvesting. 

PMID- 25567886
TI  - Size-selective fishing gear and life history evolution in the Northeast Arctic
      cod.
AB  - Industrial fishing has been identified as a cause for life history changes in
      many harvested stocks, mainly because of the intense fishing mortality and its
      size-selectivity. Because these changes are potentially evolutionary, we
      investigate evolutionarily stable life-histories and yield in an energy
      allocation state-dependent model for Northeast Arctic cod Gadus morhua. We focus
      on the evolutionary effects of size-selective fishing because regulation of gear
      selectivity may be an efficient management tool. Trawling, which harvests fish
      above a certain size, leads to early maturation except when fishing is low and
      confined to mature fish. Gillnets, where small and large fish escape, lead to
      late maturation for low to moderate harvest rates, but when harvest rates
      increase maturation age suddenly drops. This is because bell-shaped selectivity
      has two size-refuges, for fish that are below and above the harvestable size
      classes. Depending on the harvest rate it either pays to grow through the
      harvestable slot and mature above it, or mature small below it. Sustainable yield
      on the evolutionary time-scale is highest when fishing is done by trawling, but
      only for a small parameter region. Fishing with gillnets is better able to
      withstand life-history evolution, and maintains yield over a wider range of
      fishing intensities. 

PMID- 25567887
TI  - Propensity of marine reserves to reduce the evolutionary effects of fishing in a
      migratory species.
AB  - Evolutionary effects of fishing can have unwanted consequences diminishing a
      fishery's value and sustainability. Reserves, or no-take areas, have been
      proposed as a management tool for reducing fisheries-induced selection, but their
      effectiveness for migratory species has remained unexplored. Here we develop an
      eco-genetic model to predict the effects of marine reserves on fisheries-induced
      evolution under migration. To represent a stock that undergoes an annual
      migration between feeding and spawning grounds, we draw model parameters from
      Atlantic cod (Gadus morhua) in the northern part of its range. Our analysis leads
      to the following conclusions: (i) a reserve in a stock's feeding grounds,
      protecting immature and mature fish alike, reduces fisheries-induced evolution,
      even though protected and unprotected population components mix on the spawning
      grounds; (ii) in contrast, a reserve in a stock's spawning grounds, protecting
      only mature fish, has little mitigating effects on fisheries-induced evolution
      and can sometimes even exacerbate its magnitude; (iii) evolutionary changes that
      are already underway may be difficult to reverse with a reserve; (iv) directly
      after a reserve is created or enlarged, most reserve scenarios result in yield
      losses; and (v) timescale is very important: short-term yield losses immediately
      after a reserve's creation can give way to long-term gains. 

PMID- 25567888
TI  - Implications of fisheries-induced evolution for stock rebuilding and recovery.
AB  - Worldwide depletion of fish stocks has led fisheries managers to become
      increasingly concerned about rebuilding and recovery planning. To succeed,
      factors affecting recovery dynamics need to be understood, including the role of
      fisheries-induced evolution. Here we investigate a stock's response to fishing
      followed by a harvest moratorium by analyzing an individual-based evolutionary
      model parameterized for Atlantic cod Gadus morhua from its northern range,
      representative of long-lived, late-maturing species. The model allows evolution
      of life-history processes including maturation, reproduction, and growth. It also
      incorporates environmental variability, phenotypic plasticity, and density
      dependent feedbacks. Fisheries-induced evolution affects recovery in several
      ways. The first decades of recovery were dominated by demographic and density
      dependent processes. Biomass rebuilding was only lightly influenced by fisheries
      induced evolution, whereas other stock characteristics such as maturation age,
      spawning stock biomass, and recruitment were substantially affected, recovering
      to new demographic equilibria below their preharvest levels. This is because
      genetic traits took thousands of years to evolve back to preharvest levels,
      indicating that natural selection driving recovery of these traits is weaker than
      fisheries-induced selection was. Our results strengthen the case for proactive
      management of fisheries-induced evolution, as the restoration of genetic traits
      altered by fishing is slow and may even be impractical. 

PMID- 25567889
TI  - Mitigating fisheries-induced evolution in lacustrine brook charr (Salvelinus
      fontinalis) in southern Quebec, Canada.
AB  - Size-selective mortality caused by fishing can impose strong selection on
      harvested fish populations, causing evolution in important life-history traits.
      Understanding and predicting harvest-induced evolutionary change can help
      maintain sustainable fisheries. We investigate the evolutionary sustainability of
      alternative management regimes for lacustrine brook charr (Salvelinus fontinalis)
      fisheries in southern Canada and aim to optimize these regimes with respect to
      the competing objectives of maximizing mean annual yield and minimizing
      evolutionary change in maturation schedules. Using a stochastic simulation model
      of brook charr populations consuming a dynamic resource, we investigate how
      harvesting affects brook charr maturation schedules. We show that when
      approximately 5% to 15% of the brook charr biomass is harvested, yields are high,
      and harvest-induced evolutionary changes remain small. Intensive harvesting (at
      approximately >15% of brook charr biomass) results in high average yields and
      little evolutionary change only when harvesting is restricted to brook charr
      larger than the size at 50% maturation probability at the age of 2 years.
      Otherwise, intensive harvesting lowers average yield and causes evolutionary
      change in the maturation schedule of brook charr. Our results indicate that
      intermediate harvesting efforts offer an acceptable compromise between avoiding
      harvest-induced evolutionary change and securing high average yields. 

PMID- 25567890
TI  - Eco-genetic model to explore fishing-induced ecological and evolutionary effects
      on growth and maturation schedules.
AB  - Eco-genetic individual-based models involve tracking the ecological dynamics of
      simulated individual organisms that are in part characterized by heritable
      parameters. We developed an eco-genetic individual-based model to explore
      ecological and evolutionary interactions of fish growth and maturation schedules.
      Our model is flexible and allows for exploration of the effects of heritable
      growth rates (based on von Bertalanffy and biphasic growth patterns), heritable
      maturation schedules (based on maturation reaction norm concepts), or both on
      individual- and population-level traits. In baseline simulations with rather
      simple ecological trade-offs and over a relatively short time period (<200
      simulation years), simulated male and female fish evolve differential genetic
      growth and maturation. Further, resulting patterns of genetically determined
      growth and maturation are influenced by mortality rate and density-dependent
      processes, and maturation and growth parameters interact to mediate the evolution
      of one another. Subsequent to baseline simulations, we conducted experimental
      simulations to mimic fisheries harvest with two size-limits (targeting large or
      small fish), an array of fishing mortality rates, and assuming a deterministic or
      stochastic environment. Our results suggest that fishing with either size-limit
      may induce considerable changes in life-history trait expression (maturation
      schedules and growth rates), recruitment, and population abundance and structure.
      However, targeting large fish would cause more adverse genetic effects and may
      lead to a population less resilient to environmental stochasticity. 

PMID- 25567891
TI  - Avian influenza at both ends of a migratory flyway: characterizing viral genomic
      diversity to optimize surveillance plans for North America.
AB  - Although continental populations of avian influenza viruses are genetically
      distinct, transcontinental reassortment in low pathogenic avian influenza (LPAI)
      viruses has been detected in migratory birds. Thus, genomic analyses of LPAI
      viruses could serve as an approach to prioritize species and regions targeted by
      North American surveillance activities for foreign origin highly pathogenic avian
      influenza (HPAI). To assess the applicability of this approach, we conducted a
      phylogenetic and population genetic analysis of 68 viral genomes isolated from
      the northern pintail (Anas acuta) at opposite ends of the Pacific migratory
      flyway in North America. We found limited evidence for Asian LPAI lineages on
      wintering areas used by northern pintails in California in contrast to a higher
      frequency on breeding locales of Alaska. Our results indicate that the number of
      Asian LPAI lineages observed in Alaskan northern pintails, and the nucleotide
      composition of LPAI lineages, is not maintained through fall migration.
      Accordingly, our data indicate that surveillance of Pacific Flyway northern
      pintails to detect foreign avian influenza viruses would be most effective in
      Alaska. North American surveillance plans could be optimized through an analysis
      of LPAI genomics from species that demonstrate evolutionary linkages with
      European or Asian lineages and in regions that have overlapping migratory flyways
      with areas of HPAI outbreaks. 

PMID- 25567893
TI  - Climate change alters reproductive isolation and potential gene flow in an annual
      plant.
AB  - Climate change will likely cause evolution due not only to selection but also to
      changes in reproductive isolation within and among populations. We examined the
      effects of a natural drought on the timing of flowering in two populations of
      Brassica rapa and the consequences for predicted reproductive isolation and
      potential gene flow. Seeds were collected before and after a 5-year drought in
      southern California from two populations varying in soil moisture. Lines derived
      from these seeds were raised in the greenhouse under wet and drought conditions.
      We found that the natural drought caused changes in reproductive timing and that
      the changes were greater for plants from the wet than from the dry site. This
      differential shift caused the populations to become more phenological similar,
      which should lead to less reproductive isolation and increased gene flow. We
      estimated a high level of assortative mating by flowering time, which potentially
      contributed to the rapid evolution of phenological traits following the drought.
      Estimates of assortative mating were higher for the wet site population, and
      assortative mating was reduced following the drought. This study shows that
      climate change can potentially alter gene flow and reproductive isolation within
      and among populations, strongly influencing evolution. 

PMID- 25567892
TI  - Towards evolution-proof malaria control with insecticides.
AB  - As many strategies to control malaria use insecticides against adult mosquitoes,
      control is undermined by the continual evolution of resistant mosquitoes. Here we
      suggest that using alternative insecticides, or conventional insecticides in
      alternative ways might enable effective control, but delay considerably or
      prevent the evolution of resistance. Our reasoning relies on an epidemiological
      and an evolutionary principle: (i) the epidemiology of malaria is strongly
      influenced by the life-span of mosquitoes, as most infected mosquitoes die before
      the malaria parasite has completed its development; and (ii) evolutionary
      pressure is strongest in young individuals, for selection on individuals that
      have completed most of their reproduction has little evolutionary effect. It
      follows from these principles, first, that insecticides that kill mosquitoes
      several days after exposure can delay considerably the evolution of resistance
      and, second, that the evolution of resistance against larvicides can actually
      benefit control, if it is associated with shorter life-span or reduced biting in
      adults. If a late-acting insecticide and a larvicide are combined, the evolution
      of resistance against larvicides can in some circumstances prevent the evolution
      of resistance against the more effective, late-acting insecticide, leading to
      sustainable, effective control. We discuss several potential options to create
      such insecticides, focussing on biopesticides. 

PMID- 25567894
TI  - Population-specific gene expression responses to hybridization between farm and
      wild Atlantic salmon.
AB  - Because of intrinsic differences in their genetic architectures, wild populations
      invaded by domesticated individuals could experience population-specific
      consequences following introgression by genetic material of domesticated origin.
      Expression levels of 16 000 transcripts were quantified by microarrays in liver
      tissue from farm, wild, and farm-wild backcross (i.e. F1 farm-wild hybrid * wild;
      total n = 50) Atlantic salmon (Salmo salar) raised under common environmental
      conditions. The wild populations and farm strain originated from three North
      American rivers in eastern Canada (Stewiacke, Tusket, and Saint John rivers,
      respectively). Analysis of variance revealed 177 transcripts with different
      expression levels among the five strains compared. Five times more of these
      transcripts were differentiated between farmed parents and Tusket backcrosses (n
      = 53) than between Stewiacke backcrosses and their farmed parents (n = 11).
      Altered biological processes in backcrosses also differed between populations
      both in number and in the type of processes impacted (metabolism vs immunity).
      Over-dominant gene expression regulation in backcrosses varied considerably
      between populations (23% in Stewiacke vs 44% in Tusket). Hence, the consequences
      of introgression of farm genetic material on gene expression depended on
      population-specific genetic architectures. These results support the need to
      evaluate impacts of farm-wild genetic interactions at the population scale. 

PMID- 25567896
TI  - Quantifying six decades of fishery selection for size and age at maturity in
      sockeye salmon.
AB  - Life history traits of wild animals can be strongly influenced, both
      phenotypically and evolutionarily, by hunting and fishing. However, few studies
      have quantified fishery selection over long time periods. We used 57 years of
      catch and escapement data to document the magnitude of and trends in gillnet
      selection on age and size at maturity of a commercially and biologically
      important sockeye salmon stock. Overall, the fishery has caught larger fish than
      have escaped to spawn, but selection has varied over time, becoming weaker and
      less consistent recently. Selection patterns were strongly affected by fish age
      and sex, in addition to extrinsic factors including fish abundance, mesh size
      regulations, and fish length variability. These results revealed a more complex
      and changing pattern of selective harvest than the 'larger is more vulnerable'
      model, emphasizing the need for quantified, multi-year studies before conclusions
      can be drawn about potential evolutionary and ecological effects of fishery
      selection. Furthermore, the results indicate that biologically robust escapement
      goals and prevention of harvest of the largest individuals may help prevent
      negative effects of size-selective harvest. 

PMID- 25567895
TI  - Linkage disequilibrium and population structure in wild and domesticated
      populations of Phaseolus vulgaris L.
AB  - Together with the knowledge of the population structure, a critical aspect for
      the planning of association and/or population genomics studies is the level of
      linkage disequilibrium (LD) that characterizes the species and the population
      used for such an analysis. We have analyzed the population structure and LD in
      wild and domesticated populations of Phaseolus vulgaris L. using amplified
      fragment length polymorphism markers, most of which were genetically mapped in
      two recombinant inbred populations. Our results reflect the previous knowledge of
      the occurrence of two major wild gene pools of P. vulgaris, from which two
      independent domestication events originated, one in the Andes and one in
      Mesoamerica. The high level of LD in the whole sample was mostly due to the gene
      pool structure, with a much higher LD in domesticated compared to wild
      populations. In relation to association studies, our results also suggest that
      whole-genome-scan approaches are feasible in the common bean. Interestingly, an
      excess of inter-chromosomal LD was found in the domesticated populations, which
      suggests an important role for epistatic selection during domestication.
      Moreover, our results indicate the occurrence of a strong bottleneck in the
      Andean wild population before domestication, suggesting a Mesoamerican origin of
      P. vulgaris. Finally, our data support the occurrence of a single domestication
      event in Mesoamerica, and the same scenario in the Andes. 

PMID- 25567897
TI  - A case of isolation by distance and short-term temporal stability of population
      structure in brown trout (Salmo trutta) within the River Dart, southwest England.
AB  - Salmonid fishes exhibit high levels of population differentiation. In particular,
      the brown trout (Salmo trutta L.) demonstrates complex within river drainage
      genetic structure. Increasingly, these patterns can be related to the underlying
      evolutionary models, of which three scenarios (member-vagrant hypothesis,
      metapopulation model and panmixia) facilitate testable predictions for
      investigations into population structure. We analysed 1225 trout collected from
      the River Dart, a 75 km long river located in southwest England. Specimens were
      collected from 22 sample sites across three consecutive summers (2001-2003) and
      genetic variation was examined at nine microsatellite loci. A hierarchical
      analysis of molecular variance revealed that negligible genetic variation was
      attributed among temporal samples. The highest levels of differentiation occurred
      among samples isolated above barriers to fish movement, and once these samples
      were removed, a significant effect of isolation-by-distance was observed. These
      results suggest that, at least in the short-term, ecological events are more
      important in shaping the population structure of Dart trout than stochastic
      extinction events, and certainly do not contradict the expectations of a member
      vagrant hypothesis. Furthermore, individual-level spatial autocorrelation
      analyses support previous recommendations for the preservation of a number of
      spawning sites spaced throughout the tributary system to conserve the high levels
      of genetic variation identified in salmonid species. 

PMID- 25567898
TI  - Genetic control of invasive plants species using selfish genetic elements.
AB  - Invasive plants cause substantial environmental damage and economic loss. Here,
      we explore the possibility that a selfish genetic element found in plants called
      cytoplasmic male sterility (CMS) could be exploited for weed control. CMS is
      caused by mutations in the mitochondrial genome that sterilize male reproductive
      organs. We developed an analytical model and a spatial simulation to assess the
      use of CMS alleles to manage weed populations. Specifically, we examined how
      fertility, selfing, pollen limitation and dispersal influenced extinction rate
      and time until extinction in populations where CMS arises. We found that the
      introduction of a CMS allele can cause rapid population extinction, but only
      under a restricted set of conditions. Both models suggest that the CMS strategy
      will be appropriate for species where pollen limitation is negligible, inbreeding
      depression is high and the fertility advantage of females over hermaphrodites is
      substantial. In general, spatial structure did not have a strong influence on the
      simulation outcome, although low pollen dispersal and intermediate levels of seed
      dispersal tended to reduce population extinction rates. Given these results, the
      introduction of CMS alleles into a population of invasive plants probably
      represents an effective control method for only a select number of species. 

PMID- 25567899
TI  - Modeling environmentally associated morphological and genetic variation in a
      rainforest bird, and its application to conservation prioritization.
AB  - To better understand how environment shapes phenotypic and genetic variation, we
      explore the relationship between environmental variables across Ecuador and
      genetic and morphological variation in the wedge-billed woodcreeper
      (Glyphorynchus spirurus), a common Neotropical rainforest bird species.
      Generalized dissimilarity models show that variation in amplified fragment length
      polymorphism markers was strongly associated with environmental variables on both
      sides of the Andes, but could also partially be explained by geographic distance
      on the western side of the Andes. Tarsus, wing, tail, and bill lengths and bill
      depth were well explained by environmental variables on the western side of the
      Andes, whereas only tarsus length was well explained on the eastern side. Regions
      that comprise the highest rates of genetic and phenotypic change occur along
      steep elevation gradients in the Andes. Such environmental gradients are likely
      to be particularly important for maximizing adaptive diversity to minimize the
      impacts of climate change. Using a framework for conservation prioritization
      based on preserving ecological and evolutionary processes, we found little
      overlap between currently protected areas in Ecuador and regions we predicted to
      be important in maximizing adaptive variation. 

PMID- 25567900
TI  - Microarray analysis yields candidate markers for rotation resistance in the
      western corn rootworm beetle, Diabrotica virgifera virgifera.
AB  - As pest species may evolve resistance to chemical controls, they may also evolve
      resistance to cultural control methods. Yearly rotation of corn (Zea mays) with
      another crop interrupts the life cycle of the western corn rootworm beetle
      (Diabrotica virgifera virgifera, Coleoptera: Chrysomelidae), but behavioral
      resistance to crop rotation is now a major problem in the Midwest of the USA.
      Resistant adult females exhibit reduced fidelity to corn as a host and lay their
      eggs in the soil of both corn and soybean (Glycine max) fields. Behavioral assays
      suggest that the adaptation is related to increased locomotor activity, but
      finding molecular markers has been difficult. We used microarray analysis to
      search for gene expression differences between resistant and wild-type beetles.
      Candidates validated with real-time polymerase chain reaction exhibit predicted
      patterns from the microarray in independent samples across time and space. Many
      genes more highly expressed in the rotation-resistant females have no matches to
      known proteins, and most genes that were more lowly expressed are involved in
      antimicrobial defense. 

PMID- 25567901
TI  - Genetic estimates of contemporary effective population size in an endangered
      butterfly indicate a possible role for genetic compensation.
AB  - The effective population size (N e ) is a critical evolutionary and conservation
      parameter that can indicate the adaptive potential of populations. Robust
      estimates of N e of endangered taxa have been previously hampered by estimators
      that are sensitive to sample size. We estimated N e on two remaining populations
      of the endangered Miami blue butterfly, a formerly widespread taxon in Florida.
      Our goal was to determine the consistency of various temporal and point
      estimators on inferring N e and to determine the utility of this information for
      understanding the role of genetic stochasticity. We found that recently developed
      'unbiased estimators' generally performed better than some older methods in that
      the former had more realistic N e estimates and were more consistent with what is
      known about adult population size. Overall, N e /N ratios based on census point
      counts were high. We suggest that this pattern may reflect genetic compensation
      caused by reduced reproductive variance due to breeding population size not being
      limited by resources. Assuming N e and N are not heavily biased, it appears that
      the lack of gene flow between distant populations may be a greater genetic threat
      in the short term than the loss of heterozygosity due to inbreeding. 

PMID- 25567902
TI  - Hybridization and invasion: one of North America's most devastating invasive
      plants shows evidence for a history of interspecific hybridization.
AB  - Hybridization has been hypothesized to influence invasion through the generation
      of novel phenotypes and/or increased levels of genetic variance. Based on
      morphology, hybrids between diffuse knapweed and spotted knapweed, two invasive
      plants in North America, are present in the invaded range. Some individuals
      within most diffuse knapweed sites in North America exhibit intermediate diffuse
      * spotted floral morphology. We examined hybridization at the molecular level,
      using amplified fragment length polymorphisms. Approximately a quarter of the
      assayed North American diffuse knapweed individuals exhibited evidence of
      introgression from spotted knapweed. However, plants with intermediate morphology
      did not show evidence of mixed ancestry more often than the plants with typical
      diffuse knapweed morphology. The high proportion of hybrid individuals in North
      American diffuse knapweed sites found here, combined with evidence from recent
      studies, suggests that diffuse knapweed was likely introduced with admixed
      individuals, and the hybrids are not newly created postintroduction. A century of
      backcrossing with diffuse knapweed has likely decoupled the relationship between
      morphology and admixture at the molecular level. In contrast to the scenario
      encountered in North America, in the native range where diploid diffuse and
      spotted knapweed overlap, hybrid swarms are common. In such sites, the floral
      phenotype aligns more closely with the genotype. 

PMID- 25567904
TI  - Rapid evolution of morphology and adaptive life history in the invasive
      California wild radish (Raphanus sativus) and the implications for management.
AB  - Understanding the evolution and demography of invasive populations may be key for
      successful management. In this study, we test whether or not populations of the
      non-native, hybrid-derived California wild radish have regionally adapted to
      divergent climates over their 150-year history in California and determine if
      population demographic dynamics might warrant different region-specific
      strategies for control. Using a reciprocal transplant approach, we found evidence
      for genetically based differences both between and among northern, coastal and
      southern, inland populations of wild radish. Individual fitness was analyzed
      using a relatively new statistical method called 'aster modeling' which
      integrates temporally sequential fitness measurements. In their respective home
      environments, fitness differences strongly favored southern populations and only
      slightly favored northern populations. Demographic rates of transition and
      sensitivities also differed between regions of origin, suggesting that the most
      effective approach for reducing overall population growth rate would be to target
      different life-history stages in each region. 

PMID- 25567903
TI  - Evolutionary genomics of human intellectual disability.
AB  - Previous studies have postulated that X-linked and autosomal genes underlying
      human intellectual disability may have also mediated the evolution of human
      cognition. We have conducted the first comprehensive assessment of the extent and
      patterns of positive Darwinian selection on intellectual disability genes in
      humans. We report three main findings. First, as noted in some previous reports,
      intellectual disability genes with primary functions in the central nervous
      system exhibit a significant concentration to the X chromosome. Second, there was
      no evidence for a higher incidence of recent positive selection on X-linked than
      autosomal intellectual disability genes, nor was there a higher incidence of
      selection on such genes overall, compared to sets of control genes. However, the
      X-linked intellectual disability genes inferred to be subject to recent positive
      selection were concentrated in the Rho GTP-ase pathway, a key signaling pathway
      in neural development and function. Third, among all intellectual disability
      genes, there was evidence for a higher incidence of recent positive selection on
      genes involved in DNA repair, but not for genes involved in other functions.
      These results provide evidence that alterations to genes in the Rho GTP-ase and
      DNA-repair pathways may play especially-important roles in the evolution of human
      cognition and vulnerability to genetically-based intellectual disability. 

PMID- 25567905
TI  - Environmental factors associated with reproductive barrier breakdown in sympatric
      trout populations on Vancouver Island.
AB  - The incidence of hybridization between coastal cutthroat (Oncorhynchus clarki
      clarki) and rainbow trout (Oncorhynchus mykiss) varies widely among populations.
      The breakdown of reproductive isolation is of concern to managers, and raises the
      question: how have the two species retained their genetic and morphological
      divergence? Using a combination of mitochondrial DNA and nuclear DNA markers
      coupled with watershed attribute and disturbance data, we determined the
      distribution and frequency of trout hybridization on Vancouver Island, BC and the
      environmental factors associated with the hybridization. We found 284 hybrids
      (among 1004 fish) in 29 of 36 sampled populations. High variation in levels of
      hybridization was observed among populations, and no single environmental factor
      was found to dominate in determining hybridization levels. However, logging
      activity, urban infrastructure development, and stocking of hatchery rainbow
      trout played significant roles in determining hybridization levels, and
      populations in small watersheds are more at risk of reproductive barrier
      breakdown. This study illustrates that cutthroat-rainbow trout reproductive
      barrier breakdown is widespread on Vancouver Island and that anthropogenic
      disturbance plays a role in the process. As similar environmental disturbance is
      common in much of coastal trout habitat, large-scale hybridization may be
      occurring elsewhere and thus may represent a critical management issue for
      Pacific trout species. 

PMID- 25567906
TI  - Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency
      to mTORC1.
AB  - The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master
      growth regulator that responds to multiple environmental cues. Amino acids
      stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent
      fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts
      with its activator Rheb. Here, we identify SLC38A9, an uncharacterized protein
      with sequence similarity to amino acid transporters, as a lysosomal transmembrane
      protein that interacts with the Rag guanosine triphosphatases (GTPases) and
      Ragulator in an amino acid-sensitive fashion. SLC38A9 transports arginine with a
      high Michaelis constant, and loss of SLC38A9 represses mTORC1 activation by amino
      acids, particularly arginine. Overexpression of SLC38A9 or just its Ragulator
      binding domain makes mTORC1 signaling insensitive to amino acid starvation but
      not to Rag activity. Thus, SLC38A9 functions upstream of the Rag GTPases and is
      an excellent candidate for being an arginine sensor for the mTORC1 pathway. 

PMID- 25567907
TI  - Metabolism. Differential regulation of mTORC1 by leucine and glutamine.
AB  - The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates
      environmental and intracellular signals to regulate cell growth. Amino acids
      stimulate mTORC1 activation at the lysosome in a manner thought to be dependent
      on the Rag small guanosine triphosphatases (GTPases), the Ragulator complex, and
      the vacuolar H(+)-adenosine triphosphatase (v-ATPase). We report that leucine and
      glutamine stimulate mTORC1 by Rag GTPase-dependent and -independent mechanisms,
      respectively. Glutamine promoted mTORC1 translocation to the lysosome in RagA and
      RagB knockout cells and required the v-ATPase but not the Ragulator. Furthermore,
      we identified the adenosine diphosphate ribosylation factor-1 GTPase to be
      required for mTORC1 activation and lysosomal localization by glutamine. Our
      results uncover a signaling cascade to mTORC1 activation independent of the Rag
      GTPases and suggest that mTORC1 is differentially regulated by specific amino
      acids. 

PMID- 25567910
TI  - Synthesizing ecology and evolution for the study of invasive species.

PMID- 25567909
TI  - Editorial: 2009 in review.

PMID- 25567908
TI  - Broad, Hybrid Capture-Based Next-Generation Sequencing Identifies Actionable
      Genomic Alterations in Lung Adenocarcinomas Otherwise Negative for Such
      Alterations by Other Genomic Testing Approaches.
AB  - PURPOSE: Broad, hybrid capture-based next-generation sequencing (NGS), as a
      clinical test, uses less tissue to identify more clinically relevant genomic
      alterations compared with profiling with multiple non-NGS tests. We set out to
      determine the frequency of such genomic alterations via this approach in tumors
      in which previous extensive non-NGS testing had not yielded a targetable driver
      alteration. EXPERIMENTAL DESIGN: We enrolled patients with lung adenocarcinoma
      with a <= 15 pack-year smoking history whose tumors previously tested "negative"
      for alterations in 11 genes (mutations in EGFR, ERBB2, KRAS, NRAS, BRAF, MAP2K1,
      PIK3CA, and AKT1 and fusions involving ALK, ROS1, and RET) via multiple non-NGS
      methods. We performed hybridization capture of the coding exons of 287 cancer
      related genes and 47 introns of 19 frequently rearranged genes and sequenced
      these to deep, uniform coverage. RESULTS: Actionable genomic alterations with a
      targeted agent based on NCCN guidelines were identified in 26% [8 of 31: EGFR
      G719A, BRAF V600E, SOCS5-ALK, HIP1-ALK, CD74-ROS1, KIF5B-RET (n = 2), CCDC6-RET].
      Seven of these patients either received or are candidates for targeted therapy.
      Comprehensive genomic profiling using this method also identified a genomic
      alteration with a targeted agent available on a clinical trial in an additional
      39% (12 of 31). CONCLUSIONS: Broad, hybrid capture-based NGS identified
      actionable genomic alterations in 65% [95% confidence interval (CI), 48%-82%] of
      tumors from never or light smokers with lung cancers deemed without targetable
      genomic alterations by earlier extensive non-NGS testing. These findings support
      first-line profiling of lung adenocarcinomas using this approach as a more
      comprehensive and efficient strategy compared with non-NGS testing. See related
      commentary by McCutcheon and Giaccone, p. 3584.

PMID- 25567911
TI  - Genetics, adaptation, and invasion in harsh environments.
AB  - We analyze mathematical models to examine how the genetic basis of fitness
      affects the persistence of a population suddenly encountering a harsh environment
      where it would go extinct without evolution. The results are relevant for novel
      introductions and for an established population whose existence is threatened by
      a sudden change in the environment. The models span a range of genetic
      assumptions, including identical loci that contribute to absolute fitness, a two
      locus quantitative genetic model with nonidentical loci, and a model with major
      and minor genes affecting a quantitative trait. We find as a general (though not
      universal) pattern that prospects for persistence narrow as more loci contribute
      to fitness, in effect because selection per locus is increasingly weakened with
      more loci, which can even overwhelm any initial enhancement of fitness that
      adding loci might provide. When loci contribute unequally to fitness, genes of
      small effect can significantly reduce extinction risk. Indeed, major and minor
      genes can interact synergistically to reduce the time needed to evolve growth.
      Such interactions can also increase vulnerability to extinction, depending not
      just on how genes interact but also on the initial genetic structure of the
      introduced, or newly invaded, population. 

PMID- 25567912
TI  - Survival of mutations arising during invasions.
AB  - When a neutral mutation arises in an invading population, it quickly either dies
      out or 'surfs', i.e. it comes to occupy almost all the habitat available at its
      time of origin. Beneficial mutations can also surf, as can deleterious mutations
      over finite time spans. We develop descriptive statistical models that quantify
      the relationship between the probability that a mutation will surf and
      demographic parameters for a cellular automaton model of surfing. We also provide
      a simple analytic model that performs well at predicting the probability of
      surfing for neutral and beneficial mutations in one dimension. The results
      suggest that factors - possibly including even abiotic factors - that promote
      invasion success may also increase the probability of surfing and associated
      adaptive genetic change, conditioned on such success. 

PMID- 25567913
TI  - Allee effects, adaptive evolution, and invasion success.
AB  - The mechanisms that facilitate success of an invasive species include both
      ecological and evolutionary processes. Investigating the evolutionary dynamics of
      founder populations can enhance our understanding of patterns of invasiveness and
      provide insight into management strategies for controlling further establishment
      of introduced populations. Our aim is to analyze the evolutionary consequences of
      ecological processes (i.e., propagule pressure and threshold density effects)
      that impact successful colonization. We address our questions using a spatially
      explicit modeling approach that incorporates dispersal, density dependent
      population growth, and selection. Our results show that adaptive evolution may
      occur in small or sparse populations, providing a means of mitigating or avoiding
      inverse density dependent effects (i.e., Allee effects). The rate at which this
      adaptation occurs is proportional to the amount of genetic variance and is a
      crucial component in assessing whether natural selection can rescue a population
      from extinction. We provide theoretical evidence for the importance of
      recognizing evolution in predicting and explaining successful biological
      invasions. 

PMID- 25567914
TI  - The global expansion of a single ant supercolony.
AB  - Ants are among the most damaging invasive species, and their success frequently
      arises from the widespread cooperation displayed by introduced populations, often
      across hundreds of kilometers. Previous studies of the invasive Argentine ant
      (Linepithema humile) have shown that introduced populations on different
      continents each contain a single, vast supercolony and, occasionally, smaller
      secondary colonies. Here, we perform inter-continental behavioral analyses among
      supercolonies in North America, Europe, Asia, Hawaii, New Zealand and Australia
      and show that these far-flung supercolonies also recognize and accept each other
      as if members of a single, globally distributed supercolony. Furthermore,
      populations also possess similar genetic and chemical profiles. However, these
      ants do show aggression toward ants from South Africa and the smaller secondary
      colonies that occur in Hawaii and California. Thus, the largest and most dominant
      introduced populations are likely descended from the same ancestral colony and,
      despite having been established more than 100 years ago, have diverged very
      little. This apparent evolutionary stasis is surprising because, in other
      species, some of the most rapid rates of evolutionary change have occurred in
      introduced populations. Given the spatial extent of the Argentine ant society we
      report here, there can be little doubt that this intercontinental supercolony
      represents the most populous known animal society. 

PMID- 25567915
TI  - Rapid evolution in a plant-pathogen interaction and the consequences for
      introduced host species.
AB  - Plant species introduced into new regions can both leave behind co-evolved
      pathogens and acquire new ones. Traits important to infection and virulence are
      subject to rapid evolutionary change in both plant and pathogen. Using
      Stemphylium solani, a native foliar necrotroph on clovers (Trifolium and
      Medicago) in California, USA, we explore how plant-fungal interactions may change
      in an invasion context. After four generations of experimental serial passage
      through multiple hosts, Stemphylium consistently showed increased infection rates
      but no consistent change in damage to the host. In a historical opportunity
      study, we compared infection and virulence across four groups of clover hosts:
      California natives, European clovers not found in California, and both California
      and European genotypes of species naturalized in California. There was
      significant variation among hosts, but no pattern across the four groups.
      However, in direct comparisons of familiar California genotypes to unfamiliar
      European genotypes of the same naturalized species, Stemphylium consistently
      infected familiar hosts more frequently, while causing less damage on them. This
      pattern is consistent with the hypothesis of adaptive evolution in both the
      pathogen (ability to infect) and the host (tolerance of infection). Together
      these results suggest the potential for rapid evolution to alter interactions
      between plant invaders and their natural enemies. 

PMID- 25567916
TI  - The extent of hybridization and its impact on the genetic diversity and
      population structure of an invasive tree, Ulmus pumila (Ulmaceae).
AB  - Ulmus pumila is considered an invasive tree in 41 of the United States. In this
      study, we examined the extent of hybridization in naturalized populations of U.
      pumila, its impact on genetic diversity and genetic structure and its potential
      role in explaining the invasion process of U. pumila. Genetic analyses indicated
      widespread hybridization with native Ulmus rubra in naturalized U. pumila
      populations. Hybridization increased the genetic diversity of U. pumila
      populations and affected their genetic structure. The level of genetic diversity
      in 'mature' accessions, many of which may represent original plantings throughout
      the USA, was high and similar to the diversity of East Asian accessions.
      Hybridization with the native red elm may play an important role in the success
      of Siberian elm as an invader in temperate regions of the USA. 

PMID- 25567917
TI  - Coevolution between native and invasive plant competitors: implications for
      invasive species management.
AB  - Invasive species may establish in communities because they are better competitors
      than natives, but in order to remain community dominants, the competitive
      advantage of invasive species must be persistent. Native species that are not
      extirpated when highly invasive species are introduced are likely to compete with
      invaders. When population sizes and genetic diversity of native species are large
      enough, natives may be able to evolve traits that allow them to co-occur with
      invasive species. Native species may also evolve to become significant
      competitors with invasive species, and thus affect the fitness of invaders.
      Invasive species may respond in turn, creating either transient or continuing
      coevolution between competing species. In addition to demographic factors such as
      population size and growth rates, a number of factors including gene flow,
      genetic drift, the number of selection agents, encounter rates, and genetic
      diversity may affect the ability of native and invasive species to evolve
      competitive ability against one another. We discuss how these factors may differ
      between populations of native and invasive plants, and how this might affect
      their ability to respond to selection. Management actions that maintain genetic
      diversity in native species while reducing population sizes and genetic diversity
      in invasive species could promote the ability of natives to evolve improved
      competitive ability. 

PMID- 25567918
TI  - The role of adaptive trans-generational plasticity in biological invasions of
      plants.
AB  - High-impact biological invasions often involve establishment and spread in
      disturbed, high-resource patches followed by establishment and spread in
      biotically or abiotically stressful areas. Evolutionary change may be required
      for the second phase of invasion (establishment and spread in stressful areas) to
      occur. When species have low genetic diversity and short selection history,
      within-generation phenotypic plasticity is often cited as the mechanism through
      which spread across multiple habitat types can occur. We show that trans
      generational plasticity (TGP) can result in pre-adapted progeny that exhibit
      traits associated with increased fitness both in high-resource patches and in
      stressful conditions. In the invasive sedge, Cyperus esculentus, maternal plants
      growing in nutrient-poor patches can place disproportional number of propagules
      into nutrient-rich patches. Using the invasive annual grass, Aegilops
      triuncialis, we show that maternal response to soil conditions can confer greater
      stress tolerance in seedlings in the form of greater photosynthetic efficiency.
      We also show TGP for a phenological shift in a low resource environment that
      results in greater stress tolerance in progeny. These lines of evidence suggest
      that the maternal environment can have profound effects on offspring success and
      that TGP may play a significant role in some plant invasions. 

PMID- 25567919
TI  - Linking concepts in the ecology and evolution of invasive plants: network
      analysis shows what has been most studied and identifies knowledge gaps.
AB  - In recent decades, a growing number of studies have addressed connections between
      ecological and evolutionary concepts in biologic invasions. These connections may
      be crucial for understanding the processes underlying invaders' success. However,
      the extent to which scientists have worked on the integration of the ecology and
      evolution of invasive plants is poorly documented, as few attempts have been made
      to evaluate these efforts in invasion biology research. Such analysis can
      facilitate recognize well-documented relationships and identify gaps in our
      knowledge. In this study, we used a network-based method for visualizing the
      connections between major aspects of ecology and evolution in the primary
      research literature. Using the family Poaceae as an example, we show that
      ecological concepts were more studied and better interconnected than were
      evolutionary concepts. Several possible connections were not documented at all,
      representing knowledge gaps between ecology and evolution of invaders. Among
      knowledge gaps, the concepts of plasticity, gene flow, epigenetics and human
      influence were particularly under-connected. We discuss five possible research
      avenues to better understand the relationships between ecology and evolution in
      the success of Poaceae, and of alien plants in general. 

PMID- 25567920
TI  - Underutilized resources for studying the evolution of invasive species during
      their introduction, establishment, and lag phases.
AB  - The early phases of biological invasions are poorly understood. In particular,
      during the introduction, establishment, and possible lag phases, it is unclear to
      what extent evolution must take place for an introduced species to transition
      from established to expanding. In this study, we highlight three disparate data
      sources that can provide insights into evolutionary processes associated with
      invasion success: biological control organisms, horticultural introductions, and
      natural history collections. All three data sources potentially provide
      introduction dates, information about source populations, and genetic and
      morphological samples at different time points along the invasion trajectory that
      can be used to investigate preadaptation and evolution during the invasion
      process, including immediately after introduction and before invasive expansion.
      For all three data sources, we explore where the data are held, their quality,
      and their accessibility. We argue that these sources could find widespread use
      with a few additional pieces of data, such as voucher specimens collected at
      certain critical time points during biocontrol agent quarantine, rearing, and
      release and also for horticultural imports, neither of which are currently done
      consistently. In addition, public access to collected information must become
      available on centralized databases to increase its utility in ecological and
      evolutionary research. 

PMID- 25567921
TI  - State-dependent life history models in a changing (and regulated) environment:
      steelhead in the California Central Valley.
AB  - We use a state dependent life history model to predict the life history
      strategies of female steelhead trout (Oncorhynchus mykiss) in altered
      environments. As a case study of a broadly applicable approach, we applied this
      model to the American and Mokelumne Rivers in central California, where steelhead
      are listed as threatened. Both rivers have been drastically altered, with highly
      regulated flows and translocations that may have diluted local adaptation.
      Nevertheless, evolutionary optimization models could successfully predict the
      life history displayed by fish on the American River (all anadromous, with young
      smolts) and on the Mokelumne River (a mix of anadromy and residency). The similar
      fitness of the two strategies for the Mokelumne suggested that a mixed strategy
      could be favored in a variable environment. We advance the management utility of
      this framework by explicitly modeling growth as a function of environmental
      conditions and using sensitivity analyses to predict likely evolutionary
      endpoints under changed environments. We conclude that the greatest management
      concern with respect to preserving anadromy is reduced survival of emigrating
      smolts, although large changes in freshwater survival or growth rates are
      potentially also important. We also demonstrate the importance of considering
      asymptotic size along with maximum growth rate. 

PMID- 25567922
TI  - Linkage disequilibrium estimates of contemporary N e using highly variable
      genetic markers: a largely untapped resource for applied conservation and
      evolution.
AB  - Genetic methods are routinely used to estimate contemporary effective population
      size (N e) in natural populations, but the vast majority of applications have
      used only the temporal (two-sample) method. We use simulated data to evaluate how
      highly polymorphic molecular markers affect precision and bias in the single
      sample method based on linkage disequilibrium (LD). Results of this study are as
      follows: (1) Low-frequency alleles upwardly bias [Formula: see text], but a
      simple rule can reduce bias to <about 10% without sacrificing much precision. (2)
      With datasets routinely available today (10-20 loci with 10 alleles; 50
      individuals), precise estimates can be obtained for relatively small populations
      (N e < 200), and small populations are not likely to be mistaken for large ones.
      However, it is very difficult to obtain reliable estimates for large populations.
      (3) With 'microsatellite' data, the LD method has greater precision than the
      temporal method, unless the latter is based on samples taken many generations
      apart. Our results indicate the LD method has widespread applicability to
      conservation (which typically focuses on small populations) and the study of
      evolutionary processes in local populations. Considerable opportunity exists to
      extract more information about N e in nature by wider use of single-sample
      estimators and by combining estimates from different methods. 

PMID- 25567923
TI  - Do male and female black-backed woodpeckers respond differently to gaps in
      habitat?
AB  - We used population- and individual-based genetic approaches to assess barriers to
      movement in black-backed woodpeckers (Picoides arcticus), a fire-specialist that
      mainly occupies the boreal forest in North America. We tested if male and female
      woodpeckers exhibited the same movement patterns using both spatially implicit
      and explicit genetic analyses to define population structure and movement
      patterns of both sexes among populations. Three genetic groups were identified, a
      large, genetically continuous population that spans from the Rocky Mountains to
      Quebec, a small isolated population in South Dakota and a separate population in
      the western portion of their distribution (Oregon). Patterns of genetic diversity
      suggest extensive gene flow mediated by both males and females within the
      continuous boreal forest. However, male-mediated gene flow is the main form of
      connectivity between the continuously distributed group and the smaller
      populations of South Dakota and Oregon that are separated by large areas of
      unforested habitat, which apparently serves as a barrier to movement of female
      woodpeckers. 

PMID- 25567924
TI  - Negative relationships between cellular immune response, Mhc class II
      heterozygosity and secondary sexual trait in the montane water vole.
AB  - Heterogeneities in immune responsiveness may affect key epidemiological
      parameters and the dynamics of pathogens. The roles of immunogenetics in these
      variations remain poorly explored. We analysed the influence of Major
      histocompatibility complex (Mhc) genes and epigamic traits on the response to
      phytohaemagglutinin in males from cyclic populations of the montane water vole
      (Arvicola scherman). Besides, we tested the relevance of lateral scent glands as
      honest signals of male quality. Our results did not corroborate neither the
      hypotheses of genome-wide heterozygosity-fitness correlation nor the Mhc
      heterozygote advantage. We found a negative relationship between Mhc
      hetetozygosity and response to phytohaemagglutinin, mediated by a specific Mhc
      homozygous genotype. Our results therefore support the hypothesis of the Arte-Dqa
      05 homozygous genotype being a 'good' Mhc variant in terms of immunogenetic
      quality. The development of the scent glands seems to be an honest signal for
      mate choice as it is negatively correlated with helminth load. The 'good gene'
      hypothesis was not validated as Arte-Dqa-05 homozygous males did not exhibit
      larger glands. Besides, the negative relationship observed between the size of
      these glands and the response to phytohaemagglutinin, mainly for Mhc homozygotes,
      corroborates the immunocompetence handicap hypothesis. The Mhc variants
      associated with larger glands remain yet to be determined. 

PMID- 25567925
TI  - Species-specific responses to landscape fragmentation: implications for
      management strategies.
AB  - Habitat fragmentation affects the integrity of many species, but little is known
      about species-specific sensitivity to fragmentation. Here, we compared the
      genetic structure of four freshwater fish species differing in their body size
      (Leuciscus cephalus; Leuciscus leuciscus; Gobio gobio and Phoxinus phoxinus)
      between a fragmented and a continuous landscape. We tested if, overall,
      fragmentation affected the genetic structure of these fish species, and if these
      species differed in their sensitivity to fragmentation. Fragmentation negatively
      affected the genetic structure of these species. Indeed, irrespective of the
      species identity, allelic richness and heterozygosity were lower, and population
      divergence was higher in the fragmented than in the continuous landscape. This
      response to fragmentation was highly species-specific, with the smallest fish
      species (P. phoxinus) being slightly affected by fragmentation. On the contrary,
      fish species of intermediate body size (L. leuciscus and G. gobio) were highly
      affected, whereas the largest fish species (L. cephalus) was intermediately
      affected by fragmentation. We discuss the relative role of dispersal ability and
      effective population size on the responses to fragmentation we report here. The
      weirs studied here are of considerable historical importance. We therefore
      conclude that restoration programmes will need to consider both this societal
      context and the biological characteristics of the species sharing this ecosystem.

PMID- 25567926
TI  - Populations of weedy crop-wild hybrid beets show contrasting variation in mating
      system and population genetic structure.
AB  - Reproductive traits are key parameters for the evolution of invasiveness in weedy
      crop-wild hybrids. In Beta vulgaris, cultivated beets hybridize with their wild
      relatives in the seed production areas, giving rise to crop-wild hybrid weed
      beets. We investigated the genetic structure, the variation in first-year
      flowering and the variation in mating system among weed beet populations
      occurring within sugar beet production fields. No spatial genetic structure was
      found for first-year populations composed of F1 crop-wild hybrid beets. In
      contrast, populations composed of backcrossed weed beets emerging from the seed
      bank showed a strong isolation-by-distance pattern. Whereas gametophytic self
      incompatibility prevents selfing in wild beet populations, all studied weed beet
      populations had a mixed-mating system, plausibly because of the introgression of
      the crop-derived Sf gene that disrupts self-incompatibility. No significant
      relationship between outcrossing rate and local weed beet density was found,
      suggesting no trends for a shift in the mating system because of environmental
      effects. We further reveal that increased invasiveness of weed beets may stem
      from positive selection on first-year flowering induction depending on the B gene
      inherited from the wild. Finally, we discuss the practical and applied
      consequences of our findings for crop-weed management. 

PMID- 25567929
TI  - Ontogenetic selection on hatchery salmon in the wild: natural selection on
      artificial phenotypes.
AB  - Captive rearing often alters the phenotypes of organisms that are destined for
      release into the wild. Natural selection on these unnatural phenotypes could have
      important consequences for the utility of captive rearing as a restoration
      approach. We show that normal hatchery practices significantly advance the
      development of endangered Atlantic salmon (Salmo salar) fry by 30+ days. As a
      result, hatchery fry might be expected to face strong natural selection resulting
      from their developmental asynchrony. We investigated patterns of ontogenetic
      selection acting on hatchery produced salmon fry by experimentally manipulating
      fry development stage at stocking. Contrary to simple predictions, we found
      evidence for strong stabilizing selection on the ontogeny of unfed hatchery fry,
      with weaker evidence for positive directional selection on the ontogeny of fed
      fry. These selection patterns suggest a seasonally independent tradeoff between
      abiotic or biotic selection favoring advanced development and physiological
      selection linked to risk of starvation in unfed fry. We show, through a heuristic
      exercise, how such selection on ontogeny may exacerbate problems in restoration
      efforts by impairing fry productivity and reducing effective population sizes by
      13-81%. 

PMID- 25567928
TI  - Spatial genetic structure of Aedes aegypti mosquitoes in mainland Southeast Asia.
AB  - Aedes aegypti mosquitoes originated in Africa and are thought to have spread
      recently to Southeast Asia, where they are the major vector of dengue. Thirteen
      microsatellite loci were used to determine the genetic population structure of A.
      aegypti at a hierarchy of spatial scales encompassing 36 sites in Myanmar,
      Cambodia and Thailand, and two sites in Sri Lanka and Nigeria. Low, but
      significant, genetic structuring was found at all spatial scales (from 5 to >2000
      km) and significant F IS values indicated genetic structuring even within 500 m.
      Spatially dependent genetic-clustering methods revealed that although spatial
      distance plays a role in shaping larger-scale population structure, it is not the
      only factor. Genetic heterogeneity in major port cities and genetic similarity of
      distant locations connected by major roads, suggest that human transportation
      routes have resulted in passive long-distance migration of A. aegypti. The
      restricted dispersal on a small spatial scale will make localized control efforts
      and sterile insect technology effective for dengue control. Conversely,
      preventing the establishment of insecticide resistance genes or spreading
      refractory genes in a genetic modification strategy would be challenging. These
      effects on vector control will depend on the relative strength of the opposing
      effects of passive dispersal. 

PMID- 25567930
TI  - Habitat-mediated size selection in endangered Atlantic salmon fry: selectional
      restoration assessment.
AB  - Preservation of adaptive variation is a top priority of many species restoration
      programs, but most restoration activities are conducted without direct knowledge
      of selection that might foster or impair adaptation and restoration goals. In
      this study, we quantified geographic variation in selection on fry size of
      endangered Atlantic salmon (Salmo salar) during the 6-week period immediately
      following stocking in the wild. We also used a model selection approach to assess
      whether habitat variables influence patterns of such selection. We found evidence
      for significant size-selection in five out of six selection trials.
      Interestingly, the strength and pattern of selection varied extensively among
      sites, and model selection suggested that this variation in phenotypic selection
      was related to geographic variation in the presence of large woody debris and the
      slope of the stream gradient. The strong selection differentials we observed
      should be a concern for endangered salmon restoration, whether they reflect
      natural processes and an opportunity to maintain adaptation, or an indicator of
      the potentially deleterious phenotypic consequences of hatchery practices. 

PMID- 25567931
TI  - Worldwide invasion by the little fire ant: routes of introduction and eco
      evolutionary pathways.
AB  - Biological invasions are generally thought to occur after human aided migration
      to a new range. However, human activities prior to migration may also play a
      role. We studied here the evolutionary genetics of introduced populations of the
      invasive ant Wasmannia auropunctata at a worldwide scale. Using microsatellite
      markers, we reconstructed the main routes of introduction of the species. We
      found three main routes of introduction, each of them strongly associated to
      human history and trading routes. We also demonstrate the overwhelming occurrence
      of male and female clonality in introduced populations of W. auropunctata, and
      suggest that this particular reproduction system is under selection in human
      modified habitats. Together with previous researches focused on native
      populations, our results suggest that invasive clonal populations may have
      evolved within human modified habitats in the native range, and spread further
      from there. The evolutionarily most parsimonious scenario for the emergence of
      invasive populations of the little fire ant might thus be a two-step process. The
      W. auropunctata case illustrates the central role of humans in biological change,
      not only due to changes in migration patterns, but also in selective pressures
      over species. 

PMID- 25567932
TI  - The skill and style to model the evolution of resistance to pesticides and drugs.
AB  - Resistance to pesticides and drugs led to the development of theoretical models
      aimed at identifying the main factors of resistance evolution and predicting the
      efficiency of resistance management strategies. We investigated the various ways
      in which the evolution of resistance has been modelled over the last three
      decades, by reviewing 187 articles published on models of the evolution of
      resistance to all major classes of pesticides and drugs. We found that (i) the
      technical properties of the model were most strongly influenced by the class of
      pesticide or drug and the target organism, (ii) the resistance management
      strategies studied were quite similar for the different classes of pesticides or
      drugs, except that the refuge strategy was mostly used in models of the evolution
      of resistance to insecticidal proteins, (iii) economic criteria were rarely used
      to evaluate the evolution of resistance and (iv) the influence of mutation,
      migration and drift on the speed of resistance development has been poorly
      investigated. We propose guidelines for the future development of theoretical
      models of the evolution of resistance. For instance, we stress the potential need
      to give more emphasis to the three evolutionary forces migration, mutation and
      genetic drift rather than simply selection. 

PMID- 25567934
TI  - Evolutionary change in agriculture: the past, present and future.

PMID- 25567933
TI  - Cryptic vector divergence masks vector-specific patterns of infection: an example
      from the marine cycle of Lyme borreliosis.
AB  - Vector organisms are implicated in the transmission of close to a third of all
      infectious diseases. In many cases, multiple vectors (species or populations) can
      participate in transmission but may contribute differently to disease ecology and
      evolution. The presence of cryptic vector populations can be particularly
      problematic as differences in infection can be difficult to evaluate and may lead
      to erroneous evolutionary and epidemiological inferences. Here, we combine site
      occupancy modeling and molecular assays to evaluate patterns of infection in the
      marine cycle of Lyme borreliosis, involving colonial seabirds, the tick Ixodes
      uriae, and bacteria of the Borrelia burgdorferi s.l. complex. In this cycle, the
      tick vector consists of multiple, cryptic (phenotypically undistinguishable but
      genetically distinct) host races that are frequently found in sympatry. Our
      results show that bacterial detection varies strongly among tick races leading to
      vector-specific biases if raw counts are used to calculate Borrelia prevalence.
      These differences are largely explained by differences in infection intensity
      among tick races. After accounting for detection probabilities, we found that
      overall prevalence in this system is higher than previously suspected and that
      certain vector-host combinations likely contribute more than others to the local
      dynamics and large-scale dispersal of Borrelia spirochetes. These results
      highlight the importance of evaluating vector population structure and accounting
      for detection probability when trying to understand the evolutionary ecology of
      vector-borne diseases. 

PMID- 25567935
TI  - Reciprocal insights into adaptation from agricultural and evolutionary studies in
      tomato.
AB  - Although traditionally separated by different aims and methodologies, research on
      agricultural and evolutionary problems shares a common goal of understanding the
      mechanisms underlying functionally important traits. As such, research in both
      fields offers potential complementary and reciprocal insights. Here, we discuss
      adaptive stress responses (specifically to water stress) as an example of
      potentially fruitful research reciprocity, where agricultural research has
      clearly produced advances that could benefit evolutionary studies, while
      evolutionary studies offer approaches and insights underexplored in crop studies.
      We focus on research on Solanum species that include the domesticated tomato and
      its wild relatives. Integrated approaches to understanding ecological adaptation
      are particularly attractive in tomato and its wild relatives: many presumptively
      adaptive phenotypic differences characterize wild species, and the physiological
      and mechanistic basis of many relevant traits and environmental responses has
      already been examined in the context of cultivated tomato and some wild species.
      We highlight four specific instances where these reciprocal insights can be
      combined to better address questions that are fundamental both to agriculture and
      evolution. 

PMID- 25567936
TI  - Evolutionary process of Bos taurus cattle in favourable versus unfavourable
      environments and its implications for genetic selection.
AB  - The evolutionary processes that have enabled Bos taurus cattle to establish
      around the globe are at the core to the future success of livestock production.
      Our study focuses on the history of cattle domestication including the last 60
      years of B. taurus breeding programmes in both favourable and unfavourable
      environments and its consequences on evolution and fitness of cattle. We discuss
      the emergence of 'production diseases' in temperate production systems and
      consider the evolutionary genetics of tropical adaptation in cattle and conclude
      that the Senepol, N'Dama, Adaptaur and Criollo breeds, among others with similar
      evolutionary trajectories, would possess genes capable of improving the
      productivity of cattle in challenging environments. Using our own experimental
      evidence from northern Australia, we review the evolution of the Adaptaur cattle
      breed which has become resistant to cattle tick. We emphasize that the knowledge
      of interactions between genotype, environment and management in the livestock
      systems will be required to generate genotypes for efficient livestock production
      that are both economically and environmentally sustainable. Livestock producers
      in the 21st century will have less reliance on infrastructure and veterinary
      products to alleviate environmental stress and more on the animal's ability to
      achieve fitness in a given production environment. 

PMID- 25567937
TI  - Missing domesticated plant forms: can artificial selection fill the gap?
AB  - In the course of their evolution, the angiosperms have radiated into most known
      plant forms and life histories. Their adaptation to a recently created habitat,
      the crop field, produced a novel form: the plant that allocates an unprecedented
      30-60% of its net productivity to sexual structures. Long-lived trees, shrubs and
      vines of this form evolved, as did annual herbs. Perennial herb forms with
      increased allocation to asexual reproduction evolved, but there are no examples
      of perennial herbs with high sexual effort. We suggest that sowing seed into
      annually tilled fields favored shorter-lived herbs because of trade-offs between
      first-year seed production and relative growth rate and/or persistence. By
      propagating cuttings, people quickly domesticated tuber crops and large woody
      plants. Perennial herbs were too small to be efficiently propagated by cuttings,
      and the association between longevity, allogamy and genetic load made rapid
      domestication by sexual cycles unlikely. Perennial grain crops do not exist
      because they could not have evolved under the original set of conditions;
      however, they can be deliberately developed today through artificial phenotypic
      and genotypic selection. 

PMID- 25567939
TI  - Individual fitness versus whole-crop photosynthesis:solar tracking tradeoffs in
      alfalfa.
AB  - Despite the optimism of some molecular biologists, natural selection among the
      wild ancestors of crops is unlikely to have missed simple genetic improvements
      that would consistently have enhanced individual fitness. Tradeoff-free
      opportunities for further improvement of crop traits like photosynthetic
      efficiency or drought tolerance may therefore be elusive. Opportunities linked to
      acceptable tradeoffs may be abundant, however. Tradeoffs between individual
      competitiveness and the collective productivity of plant communities (e.g. those
      linked to height) have been key to past increases in yield potential. Solar
      tracking by leaves could involve such tradeoffs, if photosynthetic benefits to
      tracking leaves are outweighed by increased shading of leaves lower in the
      canopy. This hypothesis was tested using rotation in the horizontal plane to
      disrupt solar tracking in alfalfa. In sparse canopies, solar tracking increased
      net canopy photosynthesis, but rarely by more than 3%. As leaf area increased,
      solar tracking tended to decrease net canopy photosynthesis, despite edge effects
      in our 1-m(2) artificial communities, which probably exaggerated net
      photosynthetic benefits of tracking. Computer modeling suggested that the season
      long effects of solar tracking on community productivity can be negative. Solar
      tracking may have persisted, nonetheless, because individuals whose leaves track
      the sun increase shading of competitors. 

PMID- 25567940
TI  - Evolutionary Agroecology: the potential for cooperative, high density, weed
      suppressing cereals.
AB  - Evolutionary theory can be applied to improve agricultural yields and/or
      sustainability, an approach we call Evolutionary Agroecology. The basic idea is
      that plant breeding is unlikely to improve attributes already favored by millions
      of years of natural selection, whereas there may be unutilized potential in
      selecting for attributes that increase total crop yield but reduce plants'
      individual fitness. In other words, plant breeding should be based on group
      selection. We explore this approach in relation to crop-weed competition, and
      argue that it should be possible to develop high density cereals that can utilize
      their initial size advantage over weeds to suppress them much better than under
      current practices, thus reducing or eliminating the need for chemical or
      mechanical weed control. We emphasize the role of density in applying group
      selection to crops: it is competition among individuals that generates the
      'Tragedy of the Commons', providing opportunities to improve plant production by
      selecting for attributes that natural selection would not favor. When there is
      competition for light, natural selection of individuals favors a defensive
      strategy of 'shade avoidance', but a collective, offensive 'shading' strategy
      could increase weed suppression and yield in the high density, high uniformity
      cropping systems we envision. 

PMID- 25567938
TI  - Group selection and social evolution in domesticated animals.
AB  - Social interactions, especially those involving competition among individuals,
      are important in domesticated livestock and in natural populations. The
      heritability of traits affected by such interactions has two components, one
      originating in the individual like that of classical traits (direct effects) and
      the other originating in other group members (indirect effects). The latter type
      of trait represents a significant source of 'hidden heritability' and it requires
      population structure and knowledge from relatives in order to access it for
      selective breeding. When ignored, competitive interactions may increase as an
      indirect response to direct selection, resulting in diminished yields. We
      illustrate how population genetic structure affects the response to selection of
      traits with indirect genetic effects using population genetic and quantitative
      genetic theory. Population genetic theory permits us to connect our results to
      the existing body of theory on kin and group selection in natural populations.
      The quantitative genetic perspective allows us to see how breeders have used
      knowledge from relatives and family selection in the domestication of plants and
      animals to improve the welfare and production of livestock by incorporating
      social genetic effects in the breeding program. We illustrate the central
      features of these models by reviewing empirical studies from domesticated
      chickens. 

PMID- 25567941
TI  - Evolutionary response of landraces to climate change in centers of crop
      diversity.
AB  - Landraces cultivated in centers of crop diversity result from past and
      contemporary patterns of natural and farmer-mediated evolutionary forces.
      Successful in situ conservation of crop genetic resources depends on continuity
      of these evolutionary processes. Climate change is projected to affect
      agricultural production, yet analyses of impacts on in situ conservation of crop
      genetic diversity and farmers who conserve it have been absent. How will crop
      landraces respond to alterations in climate? We review the roles that phenotypic
      plasticity, evolution, and gene flow might play in sustaining production,
      although we might expect erosion of genetic diversity if landrace populations or
      entire races lose productivity. For example, highland maize landraces in southern
      Mexico do not express the plasticity necessary to sustain productivity under
      climate change, but may evolve in response to altered conditions. The outcome for
      any given crop in a given region will depend on the distribution of genetic
      variation that affects fitness and patterns of climate change. Understanding
      patterns of neutral and adaptive diversity from the population to the landscape
      scale is essential to clarify how landraces conserved in situ will continue to
      evolve and how to minimize genetic erosion of this essential natural resource. 

PMID- 25567942
TI  - Crops gone wild: evolution of weeds and invasives from domesticated ancestors.
AB  - The evolution of problematic plants, both weeds and invasives, is a topic of
      increasing interest. Plants that have evolved from domesticated ancestors have
      certain advantages for study. Because of their economic importance, domesticated
      plants are generally well-characterized and readily available for ecogenetic
      comparison with their wild descendants. Thus, the evolutionary history of crop
      descendants has the potential to be reconstructed in some detail. Furthermore,
      growing crop progenitors with their problematic descendants in a common
      environment allows for the identification of significant evolutionary differences
      that correlate with weediness or invasiveness. We sought well-established
      examples of invasives and weeds for which genetic and/or ethnobotanical evidence
      has confirmed their evolution from domesticates. We found surprisingly few cases,
      only 13. We examine our list for generalizations and then some selected cases to
      reveal how plant pests have evolved from domesticates. Despite their potential
      utility, crop descendants remain underexploited for evolutionary study. Promising
      evolutionary research opportunities for these systems are abundant and worthy of
      pursuit. 

PMID- 25567943
TI  - Local origin of two vegetative compatibility groups of Fusarium oxysporum f. sp.
      vasinfectum in Australia.
AB  - Pathogenicity and genetic diversity of Fusarium oxysporum from geographically
      widespread native Gossypium populations, including a cotton growing area believed
      to be the center of origin of VCG 01111 and VCG 01112 of F. oxysporum f. sp.
      vasinfectum (Fov) in Australia, was determined using glasshouse bioassays and
      AFLPs. Five lineages (A-E) were identified among 856 isolates. Of these, 12% were
      strongly pathogenic on cotton, 10% were weakly pathogenic and designated wild
      Fov, while 78% were nonpathogenic. In contrast to the occurrence of pathogenic
      isolates in all five lineages in soils associated with wild Gossypium, in cotton
      growing areas only three lineages (A, B, E) occurred and all pathogenic isolates
      belonged to two subgroups in lineage A. One of these contained VCG 01111 isolates
      while the other contained VCG 01112 isolates. Sequence analyses of translation
      elongation factor-1alpha, mitochondrial small subunit rDNA, nitrate reductase and
      phosphate permease confirmed that Australian Fov isolates were more closely
      related to lineage A isolates of native F. oxysporum than to Fov races 1-8 found
      overseas. These results strongly support a local evolutionary origin for Fov in
      Australian cotton growing regions. 

PMID- 25567944
TI  - Exploring the evolutionary ecology of fungal endophytes in agricultural systems:
      using functional traits to reveal mechanisms in community processes.
AB  - All plants, including crop species, harbor a community of fungal endophyte
      species, yet we know little about the biotic factors that are important in
      endophyte community assembly. We suggest that the most direct route to
      understanding the mechanisms underlying community assembly is through the study
      of functional trait variation in the host and its fungal consortium. We review
      studies on crop endophytes that investigate plant and fungal traits likely to be
      important in endophyte community processes. We focus on approaches that could
      speed detection of general trends in endophyte community assembly: (i) use of the
      'assembly rules' concept to identify specific mechanisms that influence endophyte
      community dynamics, (ii) measurement of functional trait variation in plants and
      fungi to better understand endophyte community processes and plant-fungal
      interactions, and (iii) investigation of microbe-microbe interactions, and fungal
      traits that mediate them. This approach is well suited for research in
      agricultural systems, where pair-wise host-fungus interactions and mechanisms of
      fungal-fungal competition have frequently been described. Areas for consideration
      include the possibility that human manipulation of crop phenotype and deployment
      of fungal biocontrol species can significantly influence endophyte community
      assembly. Evaluation of endophyte assembly rules may help to fine-tune crop
      management strategies. 

PMID- 25567945
TI  - The interplay between the effectiveness of the grass-endophyte mutualism and the
      genetic variability of the host plant.
AB  - Neotyphodium endophytic fungi, the asexual state of Epichloe species, protect
      cool-season grasses against stresses. The outcomes of Neotyphodium-grass
      symbioses are agronomically relevant as they may affect the productivity of
      pastures. It has been suggested that the mutualism is characteristic of agronomic
      grasses and that differential rates of gene flow between both partners'
      populations are expected to disrupt the specificity of the association and, thus,
      the mutualism in wild grasses. We propose that compatibility is necessary but not
      sufficient to explain the outcomes of Neotyphodium-grass symbiosis, and advance a
      model that links genetic compatibility, mutualism effectiveness, and endophyte
      transmission efficiency. For endophytes that reproduce clonally and depend on
      allogamous hosts for reproduction and dissemination, we propose that this
      symbiosis works as an integrated entity where gene flow promotes its fitness and
      evolution. Compatibility between the host plant and the fungal endophyte would be
      high in genetically close parents; however, mutualism effectiveness and
      transmission efficiency would be low in fitness depressed host plants. Increasing
      the genetic distance of mating parents would increase mutualism effectiveness and
      transmission efficiency. This tendency would be broken when the genetic distance
      between parents is high (out-breeding depression). Our model allows for testable
      hypotheses that would contribute to understand the coevolutionary origin and
      future of the endophyte-grass mutualism. 

PMID- 25567946
TI  - Evolutionary ecology of mycorrhizal functional diversity in agricultural systems.
AB  - The root systems of most agronomic crops are colonized by diverse assemblages of
      arbuscular mycorrhizal fungi (AMF), varying in the functional benefits (e.g.
      nutrient transfer, pathogen protection, water uptake) provided to hosts. Little
      is known about the evolutionary processes that shape the composition of these
      fungal assemblages, nor is it known whether more diverse assemblages are
      beneficial to crop productivity. In this review we aim to identify the
      evolutionary selection pressures that shape AMF diversity in agricultural systems
      and explore whether promotion of AMF diversity can convincingly be linked to
      increases in agricultural productivity and/or sustainability. We then ask whether
      farmers can (and should) actively modify evolutionary selection pressures to
      increase AMF functioning. We focus on three agriculturally imposed selection
      regimes: tillage, fertilization, and continuous monoculture. We find that the
      uniform nature of these practices strongly selects for dominance of few AMF
      species. These species exhibit predictable, generally non-beneficial traits,
      namely heavy investment in reproduction at the expense of nutrient scavenging and
      transfer processes that are beneficial for hosts. A number of focus-points are
      given based on empirical and theoretical evidence that could be utilized to slow
      down negative selection pressures on AMF functioning, therein increasing crop
      benefit. 

PMID- 25567947
TI  - Evolutionary ecology of insect adaptation to Bt crops.
AB  - Transgenic crops producing Bacillus thuringiensis (Bt) toxins are used worldwide
      to control major pests of corn and cotton. Development of strategies to delay the
      evolution of pest resistance to Bt crops requires an understanding of factors
      affecting responses to natural selection, which include variation in survival on
      Bt crops, heritability of resistance, and fitness advantages associated with
      resistance mutations. The two main strategies adopted for delaying resistance are
      the refuge and pyramid strategies. Both can reduce heritability of resistance,
      but pyramids can also delay resistance by reducing genetic variation for
      resistance. Seasonal declines in the concentration of Bt toxins in transgenic
      cultivars, however, can increase the heritability of resistance. The fitness
      advantages associated with resistance mutations can be reduced by agronomic
      practices, including increasing refuge size, manipulating refuges to increase
      fitness costs, and manipulating Bt cultivars to reduce fitness of resistant
      individuals. Manipulating costs and fitness of resistant individuals on
      transgenic insecticidal crops may be especially important for thwarting evolution
      of resistance in haplodiploid and parthenogenetic pests. Field-evolved resistance
      to Bt crops in only five pests during the last 14 years suggests that the refuge
      strategy has successfully delayed resistance, but the accumulation of resistant
      pests could accelerate. 

PMID- 25567948
TI  - Adaptive management of pest resistance by Helicoverpa species (Noctuidae) in
      Australia to the Cry2Ab Bt toxin in Bollgard II(r) cotton.
AB  - In Australia, monitoring Helicoverpa species for resistance to the Cry2Ab toxin
      in second generation Bacillus thuringiensis (Bt) cotton has precisely fulfilled
      its intended function: to warn of increases in resistance frequencies that may
      lead to field failures of the technology. Prior to the widespread adoption of two
      gene Bt cotton, the frequency of Cry2Ab resistance alleles was at least 0.001 in
      H. armigera and H. punctigera. In the 5 years hence, there has been a significant
      and apparently exponential increase in the frequency of alleles conferring Cry2Ab
      resistance in field populations of H. punctigera. Herein we review the history of
      deploying and managing resistance to Bt cotton in Australia, outline the
      characteristics of the isolated resistance that likely impact on resistance
      evolution, and use a simple model to predict likely imminent resistance
      frequencies. We then discuss potential strategies to mitigate further increases
      in resistance frequencies, until the release of a third generation product. These
      include mandating larger structured refuges, applying insecticide to crops late
      in the season, and restricting the area of Bollgard II(r) cotton. The area
      planted to Bt-crops is anticipated to continue to rise worldwide; therefore the
      strategies being considered in Australia are likely to relate to other
      situations. 

PMID- 25567949
TI  - Anthropogenic disturbance and evolutionary parameters: a lemon shark population
      experiencing habitat loss.
AB  - The level of genetic variation in natural populations influences evolutionary
      potential, and may therefore influence responses to selection in the face of
      future environmental changes. By combining long-term monitoring of marked
      individuals with genetic pedigree reconstruction, we assessed whether habitat
      loss influenced genetic variation in a lemon shark (Negaprion brevirostris)
      population at an isolated nursery lagoon (Bimini, Bahamas). We also tracked
      changes in the strength and direction of natural selection. Contrary to initial
      expectations, we found that after the habitat loss neutral genetic variation
      increased, as did additive genetic variance for juvenile morphological traits
      (body length and mass). We hypothesize that these effects might result from
      philopatric behavior in females coupled with a possible influx of male genotypes
      from other nursery sites. We also found changes in the strength of selection on
      morphological traits, which weakened considerably after the disturbance; habitat
      loss therefore changed the phenotypes favored by natural selection. Because such
      human-induced shifts in the adaptive landscape may be common, we suggest that
      conservation biologists should not simply focus on neutral genetic variation per
      se, but also on assessing and preserving evolutionary parameters, such as
      additive genetic variation and selection. 

PMID- 25567950
TI  - Life-history evolution and elevated natural mortality in a population of Atlantic
      cod (Gadus morhua).
AB  - Fisheries-induced evolution has been hypothesized to delay the recovery of
      collapsed fish stocks through effects on their productivity. The cod stock in the
      southern Gulf of St. Lawrence (SGSL) collapsed in the early 1990s and has shown
      no recovery since then, due mainly to high natural mortality of adult cod. Age
      and size at maturation of SGSL cod decreased sharply over time in cohorts
      produced in the 1950s and 1960s, likely reflecting an evolutionary response to
      intensified fishing, and have remained low since then, despite severe reductions
      in fishing mortality over the past 15 years. A predicted consequence of early
      maturation is increased natural mortality due to higher costs to reproduction.
      Early maturation may be a cause of increases in natural mortality of SGSL cod in
      the 1970s but does not appear to be related to the much larger increases since
      then. Instead, the current high natural mortality of SGSL cod appears to be
      primarily a cause, rather than a consequence, of the continued early maturation
      in this population, now replacing fishing mortality as the agent of selection
      favouring early maturity. This striking example of the failure to reverse
      fisheries-induced evolution by relaxing fishing pressure emphasizes the need for
      management strategies that minimize the chances of harvest-induced genetic
      change. 

PMID- 25567951
TI  - Rapid selection against inbreeding in a wild population of a rare frog.
AB  - Populations that are small and isolated can be threatened through loss of fitness
      due to inbreeding. Nevertheless, an increased frequency of recessive homozygotes
      could increase the efficiency of selection against deleterious mutants, thus
      reducing inbreeding depression. In wild populations, observations of evolutionary
      changes determined by selection against inbreeding are few. We used
      microsatellite DNA markers to compare the genetic features of tadpoles
      immediately after hatch with those of metamorphosing froglets belonging to the
      same cohort in a small, isolated population of the threatened frog Rana latastei.
      Within a generation, the inbreeding coefficient (F IS) decreased: at hatch, F IS
      was significantly >0, whereas F IS was <0 after metamorphosis. Furthermore,
      heterozygosity increased and allelic frequencies changed over time, resulting in
      the loss of genotypes at metamorphosis that were present in hatchlings. One
      microsatellite locus exhibited atypically large F ST values, suggesting it might
      be linked to a locus under selection. These results support the hypothesis that
      strong selection against the most inbred genotypes occurred among early life
      history stages in our population. Selective forces can promote changes that can
      affect population dynamics and should be considered in conservation planning. 

PMID- 25567952
TI  - Temporally stable population-specific differences in run timing of one-sea-winter
      Atlantic salmon returning to a large river system.
AB  - The understanding of migration patterns can significantly contribute to
      conservation and management. The spawning migrations of Atlantic salmon (Salmo
      salar) cover thousands of kilometers from the feeding areas at sea to their natal
      rivers to reproduce. Migrating salmon are exposed to intensive harvest, but
      little is known of the population-specific differences in migration behavior. In
      this study, timing of return migration was investigated among one-sea-winter
      Atlantic salmon within a river system. By utilizing knowledge of the genetic
      population structure, population of origin was reliably identified for c. 1500
      fish caught in mixed stock fisheries after adopting an approach to minimize the
      complications arising from potential nonsampled populations. Results demonstrated
      significant and temporally stable differences among populations as well as
      between sexes. Generally, female salmon from tributary populations entered fresh
      water first. Run timing was not however related to in-river migration distance.
      Rather, one-sea-winter salmon from larger populations and with a higher
      proportion of multi-sea-winter females arrived later in the season. These
      findings are a significant step toward a more thorough understanding of the
      salmon migration behavior and behavioral ecology, providing concrete tools for
      the management and conservation of the remaining indigenous Atlantic salmon
      stocks. 

PMID- 25567953
TI  - Stratified dispersal and increasing genetic variation during the invasion of
      Central Europe by the western corn rootworm, Diabrotica virgifera virgifera.
AB  - Invasive species provide opportunities for investigating evolutionary aspects of
      colonization processes, including initial foundations of populations and
      geographic expansion. Using microsatellite markers and historical information, we
      characterized the genetic patterns of the invasion of the western corn rootworm
      (WCR), a pest of corn crops, in its largest area of expansion in Europe: Central
      and South-Eastern (CSE) Europe. We found that the invaded area probably
      corresponds to a single expanding population resulting from a single introduction
      of WCR and that gene flow is geographically limited within the population. In
      contrast to what is expected in classical colonization processes, an increase in
      genetic variation was observed from the center to the edge of the outbreak.
      Control measures against WCR at the center of the outbreak may have decreased
      effective population size in this area which could explain this observed pattern
      of genetic variation. We also found that small remote outbreaks in southern
      Germany and north-eastern Italy most likely originated from long-distance
      dispersal events from CSE Europe. We conclude that the large European outbreak is
      expanding by stratified dispersal, involving both continuous diffusion and
      discontinuous long-distance dispersal. This latter mode of dispersal may
      accelerate the expansion of WCR in Europe in the future. 

PMID- 25567954
TI  - Can things get worse when an invasive species hybridizes? The harlequin ladybird
      Harmonia axyridis in France as a case study.
AB  - So far, only a few studies have explicitly investigated the consequences of
      admixture for the adaptative potential of invasive populations. We addressed this
      question in the invasive ladybird Harmonia axyridis. After decades of use as a
      biological control agent against aphids in Europe and North America, H. axyridis
      recently became invasive in four continents and has now spread widely in Europe.
      Despite this invasion, a flightless strain is still sold as a biological control
      agent in Europe. However, crosses between flightless and invasive individuals
      yield individuals able to fly, as the flightless phenotype is caused by a single
      recessive mutation. We investigated the potential consequences of admixture
      between invasive and flightless biological control individuals on the invasion in
      France. We used three complementary approaches: (i) population genetics, (ii) a
      mate-choice experiment, and (iii) a quantitative genetics experiment. The
      invasive French population and the biological control strain showed substantial
      genetic differentiation, but there are no reproductive barriers between the two.
      Hybrids displayed a shorter development time, a larger size and a higher genetic
      variance for survival in starvation conditions than invasive individuals. We
      discuss the potential consequences of our results with respect to the invasion of
      H. axyridis in Europe. 

PMID- 25567955
TI  - Genetic analysis of cabbage loopers, Trichoplusia ni (Lepidoptera: Noctuidae), a
      seasonal migrant in western North America.
AB  - Long-range migrations of many wind-borne noctuid moths will have been influenced
      by the expansion of agriculture that provides greater availability of food plants
      along the migratory route. The migratory, agricultural pest, Trichoplusia ni
      (cabbage looper) over-winters in southern California and each summer migrates as
      far north as British Columbia. We explored the degree of genetic connectivity of
      populations over this migratory range. Preliminary investigation of seven
      mitochondrial gene regions found little to no variation among 13 populations,
      while partial regions of the NADH dehydrogenase subunits 1 and 4 in 42
      individuals revealed eight and six haplotypes, respectively. The pattern of
      haplotype distribution indicated genetic homogeneity of persistent populations in
      California but weak differentiation among populations further north. Four highly
      variable amplified fragment length polymorphism primer combinations generated 167
      polymorphic bands, with heterozygosity levels ranging from 0.250 to 0.302.
      Pairwise F ST values and clustering analyses also showed similarty among
      populations in California with some differentiation among populations initiated
      from the annual migration. Overall, some differentiation occurs among temporary,
      annual migratory populations but no pattern occurs with distance from the source
      population. Population subdivision in British Columbia associated with
      greenhouses has the greatest impact on genetic differentiation. 

PMID- 25567956
TI  - Conservation prioritization in widespread species: the use of genetic and
      morphological data to assess population distinctiveness in rainbow trout
      (Oncorhynchus mykiss) from British Columbia, Canada.
AB  - Prioritization of efforts to maintain biodiversity is an important component of
      conservation, but is more often applied to ecosystems or species than within
      species. We assessed distinctiveness among 27 populations of rainbow trout
      (Salmonidae: Oncorhynchus mykiss) from British Columbia, Canada, using
      microsatellite DNA variation (representing historical or contemporary demography)
      and morphology (representing adaptive variation). Standardized genetic scores,
      that is, the average deviation across individuals within populations from the
      overall genetic score generated by factorial correspondence analysis, ranged from
      1.05 to 4.90 among populations. Similar standardized morphological scores,
      generated by principal components analysis, ranged from 1.19 to 5.35. There was
      little correlation between genetic and morphological distinctiveness across
      populations, although one population was genetically and morphologically the most
      distinctive. There was, however, a significant correlation (r = 0.26, P = 0.008)
      between microsatellite (F ST) and morphological (P ST) divergence. We combined
      measures of allelic richness, genetic variation within, and divergence among,
      populations and morphological variation to provide a conservation ranking of
      populations. Our approach can be combined with other measures of biodiversity
      value (habitat, rarity, human uses, threat status) to rationalize the
      prioritization of populations, especially for widespread species where geographic
      isolation across distinct environments promotes intraspecific variability. 

PMID- 25567958
TI  - Invasive genotypes are opportunistic specialists not general purpose genotypes.
AB  - It is not clear which forms of plasticity in fitness-related traits are
      associated with invasive species. On one hand, it may be better to have a robust
      performance across environments. On the other, it may be beneficial to take
      advantage of limited favorable conditions. We chose to study a worldwide invasive
      species, Potamopyrgus antipodarum, and compare the plasticity of life-history
      traits of a sample of invasive genotypes to a sample of ancestral-range
      genotypes. We examined the responses to salinity in this freshwater snail because
      it varies spatially and temporally in the introduced range and contributes to
      variation in fitness in our system. We used a recently developed statistical
      method that quantifies aspects of differences in the shape among reaction norms.
      We found that the invasive lineages survived and reproduced with an increased
      probability at the higher salinities, and were superior to ancestral-range
      lineages in only two traits related to reproduction. Moreover, we found that in
      terms of traits related to growth, the invasive lineages have a performance
      optimum that is shifted to higher salinities than the ancestral-range lineages as
      well as having a narrower niche breadth. Contrary to the prediction of the
      general purpose genotype hypothesis, we found that invasive lineages tended to be
      opportunistic specialists. 

PMID- 25567957
TI  - Broad and fine-scale genetic analysis of white-tailed deer populations:
      estimating the relative risk of chronic wasting disease spread.
AB  - Chronic wasting disease is a transmissible spongiform encephalopathy of cervids,
      similar to sheep scrapie that has only recently been detected in wild populations
      of white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus
      hemionus) in western Canada. Relatively little is known about local transmission
      dynamics of the disease or the potential for long-distance spread. We analysed
      the population genetic structure of over 2000 white-tailed deer sampled from
      Alberta, British Columbia, and Saskatchewan using microsatellite profiles and
      mtDNA sequencing to assess the relative risk of disease spread. There was very
      little differentiation among subpopulations and a weak trend of increasing
      differentiation with geographic distance. This suggests that the potential for
      long-distance disease spread through the dispersal of infected individuals is
      possible, yet the risk of spread should gradually diminish with distance from
      infection foci. Within subpopulations, females were more related than expected by
      chance (R > 0) within a radius of approximately 500 m. Sex-biased philopatry and
      social interactions among related females may facilitate local disease
      transmission within social groups. Local herd reduction may therefore be an
      effective tool for reducing the disease prevalence when implemented at the
      appropriate spatial scale. 

PMID- 25567959
TI  - Early detection of population declines: high power of genetic monitoring using
      effective population size estimators.
AB  - Early detection of population declines is essential to prevent extinctions and to
      ensure sustainable harvest. We evaluated the performance of two N e estimators to
      detect population declines: the two-sample temporal method and a one-sample
      method based on linkage disequilibrium (LD). We used simulated data representing
      a wide range of population sizes, sample sizes and number of loci. Both methods
      usually detect a population decline only one generation after it occurs if N e
      drops to less than approximately 100, and 40 microsatellite loci and 50
      individuals are sampled. However, the LD method often out performed the temporal
      method by allowing earlier detection of less severe population declines (N e
      approximately 200). Power for early detection increased more rapidly with the
      number of individuals sampled than with the number of loci genotyped, primarily
      for the LD method. The number of samples available is therefore an important
      criterion when choosing between the LD and temporal methods. We provide
      guidelines regarding design of studies targeted at monitoring for population
      declines. We also report that 40 single nucleotide polymorphism (SNP) markers
      give slightly lower precision than 10 microsatellite markers. Our results suggest
      that conservation management and monitoring strategies can reliably use genetic
      based methods for early detection of population declines. 

PMID- 25567960
TI  - Neoadjuvant chemoradiation and surgery improves survival outcomes compared with
      definitive chemoradiation in the treatment of stage IIIA N2 non-small-cell lung
      cancer.
AB  - OBJECTIVES: The objective of this study was to compare survival in patients with
      stage IIIA (N2) non-small-cell lung cancer (NSCLC) treated with definitive
      chemoradiation (CRT) or surgery plus neoadjuvant chemoradiation or chemotherapy
      (CRTS). METHODS: A retrospective analysis of 242 patients with stage IIIA (N2)
      NSCLC treated with curative intent between 1997 and 2007, identified 215 patients
      with surgically resectable disease. Overall survival outcomes were analysed using
      the Kaplan-Meier plots, log-rank tests and Cox proportional hazards models
      adjusting for age, gender, histology, smoking history and performance status.
      Recurrences were compared using competing risks methods, including the
      proportional subdistribution hazards regression model. RESULTS: CRTS was used to
      treat 104 patients and CRT in 111. Comparing CRTS with CRT patients, median age
      was 60 vs 62, 50 (48%) vs 69 (62%) were male and 65 (62.5%) vs 60 (54%) had
      adenocarcinoma. Of CRTS patients, 83 (80%) had a lobectomy. CRTS patients
      compared with CRT patients had decreased risk of recurrence at any site [hazard
      ratio (HR) = 0. 46, 95% confidence interval (CI): 0.32-0.64 P < 0.0001], local
      recurrence (HR = 0.50, 95% CI: 0.29-0.87, P = 0.013), loco--regional recurrence
      (HR = 0.51, 95% CI: 0.33-0.78, P = 0.002) and death (HR: 0.45, 95% CI: 0.33-0.62,
      P < 0.0001) with a median survival of 4.2 years vs 1.7 years). Risk of distant
      recurrence was also reduced in the surgical group (HR: 0.57; 95% CI: 0.38-0.87, P
      = 0.017). Treatment-related mortality was low in both cohorts. CONCLUSION: For
      patients with surgically resectable stage IIIA (N2) NSCLC, neoadjuvant therapy
      plus surgery reduces loco-regional and distant recurrence and improves survival.
      Treatment-related mortality was not significantly increased compared with the
      patients treated with CRT alone.

PMID- 25567961
TI  - A systematic review of minimally invasive surgical treatment for atrial
      fibrillation: a comparison of the Cox-Maze procedure, beating-heart epicardial
      ablation, and the hybrid procedure on safety and efficacy.
AB  - There is a growing trend to perform off-bypass surgical ablation for atrial
      fibrillation (AF) because it is perceived to be safer and more effective than the
      Cox-Maze procedure with cardiopulmonary bypass (CPB) support. In this systematic
      review, we compared three minimally invasive stand-alone surgical ablation
      procedures for AF: the endocardial Cox-Maze procedure, epicardial surgical
      ablation and a hybrid epicardial surgical and catheter-based endocardial ablation
      procedure (hybrid procedure). Relevant studies were identified in MEDLINE and the
      Cochrane Database of Systematic Reviews according to the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. From 565
      initial studies, 37 were included in this review. The total number of patients
      across all studies was 1877 (range 10-139). Two studies reported on endocardial
      Cox-Maze procedures (n = 145), 26 reported on epicardial surgical ablation (n =
      1382) and 9 reported on hybrid surgical ablation (n = 350). For minimally
      invasive Cox-Maze, epicardial and hybrid groups, operative mortality rates were
      0, 0.5 and 0.9%, perioperative permanent pacemaker insertion rates were 3.5, 2.7
      and 1.5%, incidence of conversion to median sternotomy was 0, 2.4 and 2.5%, and
      reoperation for bleeding was 1.0, 1.5 and 2.2%, with mean length of stay (days)
      of 5.4, 6.0 and 4.6, respectively. At 12 months, rates of sinus rhythm
      restoration were 93, 80 and 70%, and sinus restoration without anti-arrhythmic
      medications was 87, 72 and 71%, for Cox-Maze, epicardial and hybrid procedures,
      respectively. Of the three procedures, the minimally invasive Cox-Maze procedure
      with CPB support was most effective for the treatment of stand-alone AF and had
      important safety advantages in conversion to sternotomy and major bleeding. The
      minimally invasive Cox-Maze procedure with CPB support also demonstrated the
      potential for a higher success rate 12 months following the procedure. 

PMID- 25567963
TI  - NOTA: a potent metallo-beta-lactamase inhibitor.

PMID- 25567962
TI  - The granulocyte orphan receptor CEACAM4 is able to trigger phagocytosis of
      bacteria.
AB  - Human granulocytes express several glycoproteins of the CEACAM family. One family
      member, CEACAM3, operates as a single-chain phagocytic receptor, initiating the
      detection, internalization, and destruction of a limited set of gram-negative
      bacteria. In contrast, the function of CEACAM4, a closely related protein, is
      completely unknown. This is mainly a result of a lack of a specific ligand for
      CEACAM4. By generating chimeric proteins containing the extracellular bacteria
      binding domain of CEACAM3 and the transmembrane and cytoplasmic part of CEACAM4
      (CEACAM3/4) we demonstrate that this chimeric receptor can trigger efficient
      phagocytosis of attached particles. Uptake of CEACAM3/4-bound bacteria requires
      the intact ITAM of CEACAM4, and this motif is phosphorylated by Src family PTKs
      upon receptor clustering. Furthermore, SH2 domains derived from Src PTKs, PI3K,
      and the adapter molecule Nck are recruited and associate directly with the
      phosphorylated CEACAM4 ITAM. Deletion of this sequence motif or inhibition of Src
      PTKs blocks CEACAM4-mediated uptake. Together, our results suggest that this
      orphan receptor of the CEACAM family has phagocytic function and prompt efforts
      to identify CEACAM4 ligands. 

PMID- 25567965
TI  - In light of evolution: interdisciplinary challenges in food, health, and the
      environment.

PMID- 25567964
TI  - Silver resistance in Gram-negative bacteria: a dissection of endogenous and
      exogenous mechanisms.
AB  - OBJECTIVES: To gain a more detailed understanding of endogenous (mutational) and
      exogenous (horizontally acquired) resistance to silver in Gram-negative
      pathogens, with an emphasis on clarifying the genetic bases for resistance.
      METHODS: A suite of microbiological and molecular genetic techniques was employed
      to select and characterize endogenous and exogenous silver resistance in several
      Gram-negative species. RESULTS: In Escherichia coli, endogenous resistance arose
      after 6 days of exposure to silver, a consequence of two point mutations that
      were both necessary and sufficient for the phenotype. These mutations, in ompR
      and cusS, respectively conferred loss of the OmpC/F porins and derepression of
      the CusCFBA efflux transporter, both phenotypic changes previously linked to
      reduced intracellular accumulation of silver. Exogenous resistance involved
      derepression of the SilCFBA efflux transporter as a consequence of mutation in
      silS, but was additionally contingent on expression of the periplasmic silver
      sequestration protein SilE. Silver resistance could be selected at high frequency
      (>10(-9)) from Enterobacteriaceae lacking OmpC/F porins or harbouring the sil
      operon and both endogenous and exogenous resistance were associated with modest
      fitness costs in vitro. CONCLUSIONS: Both endogenous and exogenous silver
      resistance are dependent on the derepressed expression of closely related efflux
      transporters and are therefore mechanistically similar phenotypes. The ease with
      which silver resistance can become selected in some bacterial pathogens in vitro
      suggests that there would be benefit in improved surveillance for silver
      resistant isolates in the clinic, along with greater control over use of silver
      containing products, in order to best preserve the clinical utility of silver.

PMID- 25567967
TI  - Conciliation biology: the eco-evolutionary management of permanently invaded
      biotic systems.
AB  - Biotic invaders and similar anthropogenic novelties such as domesticates,
      transgenics, and cancers can alter ecology and evolution in environmental,
      agricultural, natural resource, public health, and medical systems. The resulting
      biological changes may either hinder or serve management objectives. For example,
      biological control and eradication programs are often defeated by unanticipated
      resistance evolution and by irreversibility of invader impacts. Moreover,
      eradication may be ill-advised when nonnatives introduce beneficial functions.
      Thus, contexts that appear to call for eradication may instead demand managed
      coexistence of natives with nonnatives, and yet applied biologists have not
      generally considered the need to manage the eco-evolutionary dynamics that
      commonly result from interactions of natives with nonnatives. Here, I advocate a
      conciliatory approach to managing systems where novel organisms cannot or should
      not be eradicated. Conciliatory strategies incorporate benefits of nonnatives to
      address many practical needs including slowing rates of resistance evolution,
      promoting evolution of indigenous biological control, cultivating replacement
      services and novel functions, and managing native-nonnative coevolution.
      Evolutionary links across disciplines foster cohesion essential for managing the
      broad impacts of novel biotic systems. Rather than signaling defeat, conciliation
      biology thus utilizes the predictive power of evolutionary theory to offer
      diverse and flexible pathways to more sustainable outcomes. 

PMID- 25567968
TI  - Evolution in agriculture: the application of evolutionary approaches to the
      management of biotic interactions in agro-ecosystems.
AB  - Anthropogenic impacts increasingly drive ecological and evolutionary processes at
      many spatio-temporal scales, demanding greater capacity to predict and manage
      their consequences. This is particularly true for agro-ecosystems, which not only
      comprise a significant proportion of land use, but which also involve conflicting
      imperatives to expand or intensify production while simultaneously reducing
      environmental impacts. These imperatives reinforce the likelihood of further
      major changes in agriculture over the next 30-40 years. Key transformations
      include genetic technologies as well as changes in land use. The use of
      evolutionary principles is not new in agriculture (e.g. crop breeding,
      domestication of animals, management of selection for pest resistance), but given
      land-use trends and other transformative processes in production landscapes,
      ecological and evolutionary research in agro-ecosystems must consider such issues
      in a broader systems context. Here, we focus on biotic interactions involving
      pests and pathogens as exemplars of situations where integration of agronomic,
      ecological and evolutionary perspectives has practical value. Although their
      presence in agro-ecosystems may be new, many traits involved in these
      associations evolved in natural settings. We advocate the use of predictive
      frameworks based on evolutionary models as pre-emptive management tools and
      identify some specific research opportunities to facilitate this. We conclude
      with a brief discussion of multidisciplinary approaches in applied evolutionary
      problems. 

PMID- 25567969
TI  - Past evolutionary tradeoffs represent opportunities for crop genetic improvement
      and increased human lifespan.
AB  - The repeated evolution of complex adaptations - crop mimicry by weeds, for
      example, or CO2-concentrating C4 photosynthesis - shows the power of natural
      selection to solve difficult problems that limited fitness in past environments.
      The sophistication of natural selection's innovations contrasts with the
      relatively simple changes (e.g., increasing the expression of existing genes)
      readily achievable by today's biotechnology. Mutants with greater expression of
      these genes arose repeatedly over the course of evolution, so their present
      rarity indicates rejection by natural selection. Similarly, medical interventions
      that simply up- or down-regulate existing physiological mechanisms presumably
      recreate phenotypes also rejected by past natural selection. Some tradeoffs that
      constrained past natural selection still apply, such as those resulting from
      conservation of matter. But tradeoffs between present human goals and individual
      fitness in past environments may represent fairly easy opportunities to achieve
      our goals by reversing some effects of past selection. This point is illustrated
      with three examples, based on tradeoffs between (i) individual-plant fitness
      versus whole-crop performance, (ii) the fitness of symbionts (rhizobia) versus
      that of their legume hosts, and (iii) human fertility versus longevity in the
      context of environmental cues, such as consumption of 'famine foods', that
      predict trends in population size. 

PMID- 25567966
TI  - Evolutionary principles and their practical application.
AB  - Evolutionary principles are now routinely incorporated into medicine and
      agriculture. Examples include the design of treatments that slow the evolution of
      resistance by weeds, pests, and pathogens, and the design of breeding programs
      that maximize crop yield or quality. Evolutionary principles are also
      increasingly incorporated into conservation biology, natural resource management,
      and environmental science. Examples include the protection of small and isolated
      populations from inbreeding depression, the identification of key traits involved
      in adaptation to climate change, the design of harvesting regimes that minimize
      unwanted life-history evolution, and the setting of conservation priorities based
      on populations, species, or communities that harbor the greatest evolutionary
      diversity and potential. The adoption of evolutionary principles has proceeded
      somewhat independently in these different fields, even though the underlying
      fundamental concepts are the same. We explore these fundamental concepts under
      four main themes: variation, selection, connectivity, and eco-evolutionary
      dynamics. Within each theme, we present several key evolutionary principles and
      illustrate their use in addressing applied problems. We hope that the resulting
      primer of evolutionary concepts and their practical utility helps to advance a
      unified multidisciplinary field of applied evolutionary biology. 

PMID- 25567970
TI  - The evolution of new enzyme function: lessons from xenobiotic metabolizing
      bacteria versus insecticide-resistant insects.
AB  - Here, we compare the evolutionary routes by which bacteria and insects have
      evolved enzymatic processes for the degradation of four classes of synthetic
      chemical insecticide. For insects, the selective advantage of such degradative
      activities is survival on exposure to the insecticide, whereas for the bacteria
      the advantage is simply a matter of access to additional sources of nutrients.
      Nevertheless, bacteria have evolved highly efficient enzymes from a wide variety
      of enzyme families, whereas insects have relied upon generalist esterase-,
      cytochrome P450- and glutathione-S-transferase-dependent detoxification systems.
      Moreover, the mutant insect enzymes are less efficient kinetically and less
      diverged in sequence from their putative ancestors than their bacterial
      counterparts. This presumably reflects several advantages that bacteria have over
      insects in the acquisition of new enzymatic functions, such as a broad
      biochemical repertoire from which new functions can be evolved, large population
      sizes, high effective mutation rates, very short generation times and access to
      genetic diversity through horizontal gene transfer. Both the insect and bacterial
      systems support recent theory proposing that new biochemical functions often
      evolve from 'promiscuous' activities in existing enzymes, with subsequent
      mutations then enhancing those activities. Study of the insect enzymes will help
      in resistance management, while the bacterial enzymes are potential bioremediants
      of insecticide residues in a range of contaminated environments. 

PMID- 25567972
TI  - Ten questions for evolutionary studies of disease vulnerability.
AB  - Many evolutionary applications in medicine rely on well-established methods, such
      as population genetics, phylogenetic analysis, and observing pathogen evolution.
      Approaches to evolutionary questions about traits that leave bodies vulnerable to
      disease are less well developed. Strategies for formulating questions and
      hypotheses remain unsettled, and methods for testing evolutionary hypotheses are
      unfamiliar to many in medicine. This article uses recent examples to illustrate
      successful strategies and some common challenges. Ten questions arise in the
      course of considering hypotheses about traits that leave bodies vulnerable to
      disease. Addressing them systematically can help minimize confusion and errors. 

PMID- 25567971
TI  - How evolutionary principles improve the understanding of human health and
      disease.
AB  - An appreciation of the fundamental principles of evolutionary biology provides
      new insights into major diseases and enables an integrated understanding of human
      biology and medicine. However, there is a lack of awareness of their importance
      amongst physicians, medical researchers, and educators, all of whom tend to focus
      on the mechanistic (proximate) basis for disease, excluding consideration of
      evolutionary (ultimate) reasons. The key principles of evolutionary medicine are
      that selection acts on fitness, not health or longevity; that our evolutionary
      history does not cause disease, but rather impacts on our risk of disease in
      particular environments; and that we are now living in novel environments
      compared to those in which we evolved. We consider these evolutionary principles
      in conjunction with population genetics and describe several pathways by which
      evolutionary processes can affect disease risk. These perspectives provide a more
      cohesive framework for gaining insights into the determinants of health and
      disease. Coupled with complementary insights offered by advances in genomic,
      epigenetic, and developmental biology research, evolutionary perspectives offer
      an important addition to understanding disease. Further, there are a number of
      aspects of evolutionary medicine that can add considerably to studies in other
      domains of contemporary evolutionary studies. 

PMID- 25567973
TI  - Consequences of immunopathology for pathogen virulence evolution and public
      health: malaria as a case study.
AB  - Evolutionary theories explaining virulence-the fitness damage incurred by
      infected hosts-often focus on parasite strategies for within-host exploitation.
      However, much virulence can be caused by the host's own immune response: for
      example, pro-inflammatory cytokines, although essential for killing malaria
      parasites, also damage host tissue. Here we argue that immune-mediated virulence,
      or 'immunopathology,' may affect malaria virulence evolution and should be
      considered in the design of medical interventions. Our argument is based on the
      ability of immunopathology to disrupt positive virulence-transmission
      relationships assumed under the trade-off theory of virulence evolution. During
      rodent malaria infections, experimental reduction of inflammation using reagents
      approved for field use decreases virulence but increases parasite transmission
      potential. Importantly, rodent malaria parasites exhibit genetic diversity in the
      propensity to induce inflammation and invest in transmission-stage parasites in
      the presence of pro-inflammatory cytokines. If immunopathology positively
      correlates with malaria parasite density, theory suggests it could select for
      relatively low malaria virulence. Medical interventions which decrease
      immunopathology may therefore inadvertently select for increased malaria
      virulence. The fitness consequences to parasites of variations in immunopathology
      must be better understood in order to predict trajectories of parasite virulence
      evolution in heterogeneous host populations and in response to medical
      interventions. 

PMID- 25567975
TI  - Incorporating evolutionary principles into environmental management and policy.
AB  - As policymakers and managers work to mitigate the effects of rapid anthropogenic
      environmental changes, they need to consider organisms' responses. In light of
      recent evidence that evolution can be quite rapid, this now includes evolutionary
      responses. Evolutionary principles have a long history in conservation biology,
      and the necessary next step for the field is to consider ways in which
      conservation policy makers and managers can proactively manipulate evolutionary
      processes to achieve their goals. In this review, we aim to illustrate the
      potential conservation benefits of an increased understanding of evolutionary
      history and prescriptive manipulation of three basic evolutionary factors:
      selection, variation, and gene flow. For each, we review and propose ways that
      policy makers and managers can use evolutionary thinking to preserve threatened
      species, combat pest species, or reduce undesirable evolutionary changes. Such
      evolution-based management has potential to be a highly efficient and consistent
      way to create greater ecological resilience to widespread, rapid, and
      multifaceted environmental change. 

PMID- 25567976
TI  - Building evolutionary resilience for conserving biodiversity under climate
      change.
AB  - Evolution occurs rapidly and is an ongoing process in our environments.
      Evolutionary principles need to be built into conservation efforts, particularly
      given the stressful conditions organisms are increasingly likely to experience
      because of climate change and ongoing habitat fragmentation. The concept of
      evolutionary resilience is a way of emphasizing evolutionary processes in
      conservation and landscape planning. From an evolutionary perspective, landscapes
      need to allow in situ selection and capture high levels of genetic variation
      essential for responding to the direct and indirect effects of climate change. We
      summarize ideas that need to be considered in planning for evolutionary
      resilience and suggest how they might be incorporated into policy and management
      to ensure that resilience is maintained in the face of environmental degradation.

PMID- 25567977
TI  - Newly rare or newly common: evolutionary feedbacks through changes in population
      density and relative species abundance, and their management implications.
AB  - Environmental management typically seeks to increase or maintain the population
      sizes of desirable species and to decrease population sizes of undesirable pests,
      pathogens, or invaders. With changes in population size come long-recognized
      changes in ecological processes that act in a density-dependent fashion. While
      the ecological effects of density dependence have been well studied, the
      evolutionary effects of changes in population size, via changes in ecological
      interactions with community members, are underappreciated. Here, we provide
      examples of changing selective pressures on, or evolution in, species as a result
      of changes in either density of conspecifics or changes in the frequency of
      heterospecific versus conspecific interactions. We also discuss the management
      implications of such evolutionary responses in species that have experienced
      rapid increases or decreases in density caused by human actions. 

PMID- 25567978
TI  - Eco-evolutionary effects on population recovery following catastrophic
      disturbance.
AB  - Fine-scale genetic diversity and contemporary evolution can theoretically
      influence ecological dynamics in the wild. Such eco-evolutionary effects might be
      particularly relevant to the persistence of populations facing acute or chronic
      environmental change. However, experimental data on wild populations is currently
      lacking to support this notion. One way that ongoing evolution might influence
      the dynamics of threatened populations is through the role that selection plays
      in mediating the 'rescue effect', the ability of migrants to contribute to the
      recovery of populations facing local disturbance and decline. Here, we combine
      experiments with natural catastrophic events to show that ongoing evolution is a
      major determinant of migrant contributions to population recovery in Trinidadian
      guppies (Poecilia reticulata). These eco-evolutionary limits on migrant
      contributions appear to be mediated by the reinforcing effects of natural and
      sexual selection against migrants, despite the close geographic proximity of
      migrant sources. These findings show that ongoing adaptive evolution can be a
      double-edged sword for population persistence, maintaining local fitness at a
      cost to demographic risk. Our study further serves as a potent reminder that
      significant evolutionary and eco-evolutionary dynamics might be at play even
      where the phenotypic status quo is largely maintained generation to generation. 

PMID- 25567980
TI  - Human-induced morphological shifts in an island lizard.
AB  - Understanding the evolutionary consequences of anthropogenic change is an
      emerging topic in evolutionary biology. While highly sensitive species may go
      extinct in response to anthropogenic habitat alteration, those with broader
      environmental tolerances may persist and adapt to the changes. Here, we use
      morphological data from the brown anole (Anolis sagrei), a lizard species that
      lives in both natural and human-disturbed habitats, to examine the impact of
      anthropogenic habitat alteration. We find populations inhabiting disturbed
      habitats were significantly larger in snout-vent length, hindspan, and mass and
      provide evidence that the observed divergence in hindspan is driven by human
      induced changes in habitat structure. Populations were found to be genetically
      distinct among islands but are not genetically differentiated between habitat
      types on islands. Thus, the observed pattern of intra-island morphological
      differences cannot be explained by separate founding populations. Rather, our
      results are consistent with morphological differences between habitats having
      arisen in situ on each island. Results underscore the significant impact
      anthropogenic change may have on evolutionary trajectories of populations that
      persist in human-altered habitats. 

PMID- 25567974
TI  - The emergence of human-evolutionary medical genomics.
AB  - In this review, I describe how evolutionary genomics is uniquely suited to
      spearhead advances in understanding human disease risk, owing to the privileged
      position of genes as fundamental causes of phenotypic variation, and the ability
      of population genetic and phylogenetic methods to robustly infer processes of
      natural selection, drift, and mutation from genetic variation at the levels of
      family, population, species, and clade. I first provide an overview of models for
      the origins and maintenance of genetically based disease risk in humans. I then
      discuss how analyses of genetic disease risk can be dovetailed with studies of
      positive and balancing selection, to evaluate the degree to which the 'genes that
      make us human' also represent the genes that mediate risk of polygenic disease.
      Finally, I present four basic principles for the nascent field of human
      evolutionary medical genomics, each of which represents a process that is
      nonintuitive from a proximate perspective. Joint consideration of these
      principles compels novel forms of interdisciplinary analyses, most notably
      studies that (i) analyze tradeoffs at the level of molecular genetics, and (ii)
      identify genetic variants that are derived in the human lineage or in specific
      populations, and then compare individuals with derived versus ancestral alleles. 

PMID- 25567979
TI  - Evolution and behavioural responses to human-induced rapid environmental change.
AB  - Almost all organisms live in environments that have been altered, to some degree,
      by human activities. Because behaviour mediates interactions between an
      individual and its environment, the ability of organisms to behave appropriately
      under these new conditions is crucial for determining their immediate success or
      failure in these modified environments. While hundreds of species are suffering
      dramatically from these environmental changes, others, such as urbanized and pest
      species, are doing better than ever. Our goal is to provide insights into
      explaining such variation. We first summarize the responses of some species to
      novel situations, including novel risks and resources, habitat
      loss/fragmentation, pollutants and climate change. Using a sensory ecology
      approach, we present a mechanistic framework for predicting variation in
      behavioural responses to environmental change, drawing from models of decision
      making processes and an understanding of the selective background against which
      they evolved. Where immediate behavioural responses are inadequate, learning or
      evolutionary adaptation may prove useful, although these mechanisms are also
      constrained by evolutionary history. Although predicting the responses of species
      to environmental change is difficult, we highlight the need for a better
      understanding of the role of evolutionary history in shaping individuals'
      responses to their environment and provide suggestion for future work. 

PMID- 25567981
TI  - Mapping evolutionary process: a multi-taxa approach to conservation
      prioritization.
AB  - Human-induced land use changes are causing extensive habitat fragmentation. As a
      result, many species are not able to shift their ranges in response to climate
      change and will likely need to adapt in situ to changing climate conditions.
      Consequently, a prudent strategy to maintain the ability of populations to adapt
      is to focus conservation efforts on areas where levels of intraspecific variation
      are high. By doing so, the potential for an evolutionary response to
      environmental change is maximized. Here, we use modeling approaches in
      conjunction with environmental variables to model species distributions and
      patterns of genetic and morphological variation in seven Ecuadorian amphibian,
      bird, and mammal species. We then used reserve selection software to prioritize
      areas for conservation based on intraspecific variation or species-level
      diversity. Reserves selected using species richness and complementarity showed
      little overlap with those based on genetic and morphological variation. Priority
      areas for intraspecific variation were mainly located along the slopes of the
      Andes and were largely concordant among species, but were not well represented in
      existing reserves. Our results imply that in order to maximize representation of
      intraspecific variation in reserves, genetic and morphological variation should
      be included in conservation prioritization. 

PMID- 25567982
TI  - Bcl2 inhibits recruitment of Mre11 complex to DNA double-strand breaks in
      response to high-linear energy transfer radiation.
AB  - High-linear energy transfer ionizing radiation, derived from high charge (Z) and
      energy (E) (HZE) particles, induces clustered/complex DNA double-strand breaks
      (DSBs) that include small DNA fragments, which are not repaired by the non
      homologous end-joining (NHEJ) pathway. The homologous recombination (HR) DNA
      repair pathway plays a major role in repairing DSBs induced by HZE particles. The
      Mre11 complex (Mre11/Rad50/NBS1)-mediated resection of DSB ends is a required
      step in preparing for DSB repair via the HR DNA repair pathway. Here we found
      that expression of Bcl2 results in decreased HR activity and retards the repair
      of DSBs induced by HZE particles (i.e. (56)iron and (28)silicon) by inhibiting
      Mre11 complex activity. Exposure of cells to (56)iron or (28)silicon promotes
      Bcl2 to interact with Mre11 via the BH1 and BH4 domains. Purified Bcl2 protein
      directly suppresses Mre11 complex-mediated DNA resection in vitro. Expression of
      Bcl2 reduces the ability of Mre11 to bind DNA following exposure of cells to HZE
      particles. Our findings suggest that, after cellular exposure to HZE particles,
      Bcl2 may inhibit Mre11 complex-mediated DNA resection leading to suppression of
      the HR-mediated DSB repair in surviving cells, which may potentially contribute
      to tumor development. 

PMID- 25567983
TI  - REV7 is essential for DNA damage tolerance via two REV3L binding sites in
      mammalian DNA polymerase zeta.
AB  - DNA polymerase zeta (pol zeta) is exceptionally important for controlling
      mutagenesis and genetic instability. REV3L comprises the catalytic subunit, while
      REV7 (MAD2L2) is considered an accessory subunit. However, it has not been
      established that the role of REV7 in DNA damage tolerance is necessarily
      connected with mammalian pol zeta, and there is accumulating evidence that REV7
      and REV3L have independent functions. Analysis of pol zeta has been hampered by
      difficulties in expression of REV3L in mammalian cells, and lack of a functional
      complementation system. Here, we report that REV7 interacts with full-length
      REV3L in vivo and we identify a new conserved REV7 interaction site in human
      REV3L (residues 1993-2003), distinct from the known binding site (residues 1877
      1887). Mutation of both REV7-binding sites eliminates the REV3L-REV7 interaction.
      In vivo complementation shows that both REV7-binding sites in REV3L are necessary
      for preventing spontaneous chromosome breaks and conferring resistance to UV
      radiation and cisplatin. This demonstrates a damage-specific function of REV7 in
      pol zeta, in contrast to the distinct roles of REV3L and REV7 in primary cell
      viability and embryogenesis. 

PMID- 25567984
TI  - DNA binding by FOXP3 domain-swapped dimer suggests mechanisms of long-range
      chromosomal interactions.
AB  - FOXP3 is a lineage-specific transcription factor that is required for regulatory
      T cell development and function. In this study, we determined the crystal
      structure of the FOXP3 forkhead domain bound to DNA. The structure reveals that
      FOXP3 can form a stable domain-swapped dimer to bridge DNA in the absence of
      cofactors, suggesting that FOXP3 may play a role in long-range gene interactions.
      To test this hypothesis, we used circular chromosome conformation capture coupled
      with high throughput sequencing (4C-seq) to analyze FOXP3-dependent genomic
      contacts around a known FOXP3-bound locus, Ptpn22. Our studies reveal that FOXP3
      induces significant changes in the chromatin contacts between the Ptpn22 locus
      and other Foxp3-regulated genes, reflecting a mechanism by which FOXP3
      reorganizes the genome architecture to coordinate the expression of its target
      genes. Our results suggest that FOXP3 mediates long-range chromatin interactions
      as part of its mechanisms to regulate specific gene expression in regulatory T
      cells. 

PMID- 25567985
TI  - Multilayered genetic safeguards limit growth of microorganisms to defined
      environments.
AB  - Genetically modified organisms (GMOs) are commonly used to produce valuable
      compounds in closed industrial systems. However, their emerging applications in
      open clinical or environmental settings require enhanced safety and security
      measures. Intrinsic biocontainment, the creation of bacterial hosts unable to
      survive in natural environments, remains a major unsolved biosafety problem. We
      developed a new biocontainment strategy containing overlapping 'safeguards'
      engineered riboregulators that tightly control expression of essential genes, and
      an engineered addiction module based on nucleases that cleaves the host genome-to
      restrict viability of Escherichia coli cells to media containing exogenously
      supplied synthetic small molecules. These multilayered safeguards maintain robust
      growth in permissive conditions, eliminate persistence and limit escape
      frequencies to <1.3 * 10(-12). The staged approach to safeguard implementation
      revealed mechanisms of escape and enabled strategies to overcome them. Our
      safeguarding strategy is modular and employs conserved mechanisms that could be
      extended to clinically or industrially relevant organisms and undomesticated
      species. 

PMID- 25567986
TI  - Transcriptional regulator-mediated activation of adaptation genes triggers CRISPR
      de novo spacer acquisition.
AB  - Acquisition of de novo spacer sequences confers CRISPR-Cas with a memory to
      defend against invading genetic elements. However, the mechanism of regulation of
      CRISPR spacer acquisition remains unknown. Here we examine the transcriptional
      regulation of the conserved spacer acquisition genes in Type I-A of Sulfolobus
      islandicus REY15A. Csa3a, a MarR-like transcription factor encoded by the gene
      located adjacent to csa1, cas1, cas2 and cas4 cluster, but on the reverse strand,
      was demonstrated to specifically bind to the csa1 and cas1 promoters with the
      imperfect palindromic sequence. Importantly, it was demonstrated that the
      transcription level of csa1, cas1, cas2 and cas4 was significantly enhanced in a
      csa3a-overexpression strain and, moreover, the Csa1 and Cas1 protein levels were
      increased in this strain. Furthermore, we demonstrated the hyperactive uptake of
      unique spacers within both CRISPR loci in the presence of the csa3a
      overexpression vector. The spacer acquisition process is dependent on the CCN PAM
      sequence and protospacer selection is random and non-directional. These results
      suggested a regulation mechanism of CRISPR spacer acquisition where a single
      transcriptional regulator senses the presence of an invading element and then
      activates spacer acquisition gene expression which leads to de novo spacer uptake
      from the invading element. 

PMID- 25567987
TI  - A composite enhancer regulates p63 gene expression in epidermal morphogenesis and
      in keratinocyte differentiation by multiple mechanisms.
AB  - p63 is a crucial regulator of epidermal development, but its transcriptional
      control has remained elusive. Here, we report the identification of a long-range
      enhancer (p63LRE) that is composed of two evolutionary conserved modules (C38 and
      C40), acting in concert to control tissue- and layer-specific expression of the
      p63 gene. Both modules are in an open and active chromatin state in human and
      mouse keratinocytes and in embryonic epidermis, and are strongly bound by p63.
      p63LRE activity is dependent on p63 expression in embryonic skin, and also in the
      commitment of human induced pluripotent stem cells toward an epithelial cell
      fate. A search for other transcription factors involved in p63LRE regulation
      revealed that the CAAT enhancer binding proteins Cebpa and Cebpb and the POU
      domain-containing protein Pou3f1 repress p63 expression during keratinocyte
      differentiation by binding the p63LRE enhancer. Collectively, our data indicate
      that p63LRE is composed of additive and partly redundant enhancer modules that
      act to direct robust p63 expression selectively in the basal layer of the
      epidermis. 

PMID- 25567988
TI  - Neddylation inhibits CtIP-mediated resection and regulates DNA double strand
      break repair pathway choice.
AB  - DNA double strand breaks are the most cytotoxic lesions that can occur on the
      DNA. They can be repaired by different mechanisms and optimal survival requires a
      tight control between them. Here we uncover protein deneddylation as a major
      controller of repair pathway choice. Neddylation inhibition changes the normal
      repair profile toward an increase on homologous recombination. Indeed,
      RNF111/UBE2M-mediated neddylation acts as an inhibitor of BRCA1 and CtIP-mediated
      DNA end resection, a key process in repair pathway choice. By controlling the
      length of ssDNA produced during DNA resection, protein neddylation not only
      affects the choice between NHEJ and homologous recombination but also controls
      the balance between different recombination subpathways. Thus, protein
      neddylation status has a great impact in the way cells respond to DNA breaks. 

PMID- 25567989
TI  - Conversion of the LIN-1 ETS protein of Caenorhabditis elegans from a SUMOylated
      transcriptional repressor to a phosphorylated transcriptional activator.
AB  - The LIN-1 ETS transcription factor plays a pivotal role in controlling cell fate
      decisions during development of the Caenorhabditis elegans vulva. Prior to
      activation of the RTK/Ras/ERK-signaling pathway, LIN-1 functions as a SUMOylated
      transcriptional repressor that inhibits vulval cell fate. Here we demonstrate
      using the yeast two-hybrid system that SUMOylation of LIN-1 mediates interactions
      with a protein predicted to be involved in transcriptional repression: the RAD-26
      Mi-2beta/CHD4 component of the nucleosome remodeling and histone deacetylation
      (NuRD) transcriptional repression complex. Genetic studies indicated that rad-26
      functions to inhibit vulval cell fates in worms. Using the yeast two-hybrid
      system, we showed that the EGL-27/MTA1 component of the NuRD complex binds the
      carboxy-terminus of LIN-1 independently of LIN-1 SUMOylation. EGL-27 also binds
      UBC-9, an enzyme involved in SUMOylation, and MEP-1, a zinc-finger protein
      previously shown to bind LIN-1. Genetic studies indicate that egl-27 inhibits
      vulval cell fates in worms. These results suggest that LIN-1 recruits multiple
      proteins that repress transcription via both the SUMOylated amino-terminus and
      the unSUMOylated carboxy-terminus. Assays in cultured cells showed that the
      carboxy-terminus of LIN-1 was converted to a potent transcriptional activator in
      response to active ERK. We propose a model in which LIN-1 recruits multiple
      transcriptional repressors to inhibit the 1 degrees  vulval cell fate, and
      phosphorylation by ERK converts LIN-1 to a transcriptional activator that
      promotes the 1 degrees  vulval cell fate. 

PMID- 25567990
TI  - Recent and massive expansion of the mating-type-specific region in the smut
      fungus Microbotryum.
AB  - The presence of large genomic regions with suppressed recombination (SR) is a key
      shared property of some sex- and mating-type determining (mat) chromosomes
      identified to date in animals, plants, and fungi. Why such regions form and how
      they evolve remain central questions in evolutionary genetics. The smut fungus
      Microbotryum lychnis-dioicae is a basidiomycete fungus in which dimorphic mat
      chromosomes have been reported, but the size, age, and evolutionary dynamics of
      the SR region remains unresolved. To identify the SR region in M. lychnis-dioicae
      and to study its evolution, we sequenced 12 genomes (6 per mating type) of this
      species and identified the genomic contigs that show fixed sequence differences
      between the mating types. We report that the SR region spans more than half of
      the mat chromosome (>2.3 Mbp) and that it is of very recent origin (~2 * 10(6)
      years) as the average sequence divergence between mating types was only 2% in the
      SR region. This contrasts with a much higher divergence in and around the mating
      type determining pheromone receptor locus in the SR, suggesting a recent and
      massive expansion of the SR region. Our results comprise the first reported case
      of recent massive SR expansion documented in a basidiomycete fungus. 

PMID- 25567992
TI  - Gene-drive into insect populations with age and spatial structure: a theoretical
      assessment.
AB  - The potential benefits and risks of genetically engineered gene-drive systems for
      replacing wild pest strains with more benign strains must be assessed prior to
      any field releases. We develop a computer simulation model to assess the
      feasibility of using engineered underdominance constructs to drive transgenes
      into age- and spatially structured mosquito populations. Our practical criterion
      for success is the achievement of a transgene frequency of at least 0.80 within 3
      years of release. The impacts of a number of parameters that may affect the
      success of gene-drive, such as the release area, release age, density-dependent
      larval survival, fitness cost of the engineered genes, and migration probability
      of adults, are examined. Results show that patchy release generally requires the
      release of fewer engineered insects to achieve success than central release. When
      the fitness cost is very low, central release covering 25% of the total area can
      be more effective than a completely uniform release over the whole area. This
      study demonstrates that to determine the best method of spatial release, and the
      total number of engineered insects that must be released, it is important to take
      into account the age and sex of the released insects and spatial structure of the
      population. 

PMID- 25567991
TI  - Quality control of genotypes using heritability estimates of gene content at the
      marker.
AB  - Quality control filtering of single-nucleotide polymorphisms (SNPs) is a key step
      when analyzing genomic data. Here we present a practical method to identify low
      quality SNPs, meaning markers whose genotypes are wrongly assigned for a large
      proportion of individuals, by estimating the heritability of gene content at each
      marker, where gene content is the number of copies of a particular reference
      allele in a genotype of an animal (0, 1, or 2). If there is no mutation at the
      marker, gene content has an additive heritability of 1 by construction. The
      method uses restricted maximum likelihood (REML) to estimate heritability of gene
      content at each SNP and also builds a likelihood-ratio test statistic to test for
      zero error variance in genotyping. As a by-product, estimates of the allele
      frequencies of markers at the base population are obtained. Using simulated data
      with 10% permutation error (4% actual error) in genotyping, the method had a
      specificity of 0.96 (4% of correct markers are rejected) and a sensitivity of
      0.99 (1% of wrong markers are accepted) if markers with heritability lower than
      0.975 are discarded. Checking of Mendelian errors resulted in a lower sensitivity
      (0.84) for the same simulation. The proposed method is further illustrated with a
      real data set with genotypes from 3534 animals genotyped for 50,433 markers from
      the Illumina PorcineSNP60 chip and a pedigree of 6473 individuals; those markers
      underwent very little quality control. A total of 4099 markers with P-values
      lower than 0.01 were discarded based on our method, with associated estimates of
      heritability as low as 0.12. Contrary to other techniques, our method uses all
      information in the population simultaneously, can be used in any population with
      markers and pedigree recordings, and is simple to implement using standard
      software for REML estimation. Scripts for its use are provided. 

PMID- 25567993
TI  - Selection due to nonretention mortality in gillnet fisheries for salmon.
AB  - Fisheries often exert selective pressures through elevated mortality on a
      nonrandom component of exploited stocks. Selective removal of individuals will
      alter the composition of a given population, with potential consequences for its
      size structure, stability and evolution. Gillnets are known to harvest fish
      according to size. It is not known, however, whether delayed mortality due to
      disentanglement from gillnets exerts selective pressures that reinforce or
      counteract harvest selection. We examined gillnet disentanglement in exploited
      populations of sockeye salmon (Oncorhynchus nerka) in Bristol Bay, Alaska, to
      characterize the length distribution of fish that disentangle from gillnets and
      determine whether nonretention mortality reinforces harvest selection and exerts
      common pressures according to sex and age. We also evaluated discrete spawning
      populations to determine whether nonretention affects populations with different
      morphologies in distinct ways. In aggregate, nonretention mortality in fish that
      disentangle from gillnets counters harvest selection but with different effects
      by sex and age. At the level of individual spawning populations, nonretention
      mortality may exert stabilizing, disruptive, or directional selection depending
      on the size distribution of a given population. Our analyses suggest nonretention
      mortality exerts significant selective pressures and should be explicitly
      included in analyses of fishery-induced selection. 

PMID- 25567994
TI  - Hybridization effects on phenotypic plasticity: experimental compensatory growth
      in farmed-wild Atlantic salmon.
AB  - Compensatory growth (CG) is a means by which organisms can increase their growth
      rate above their routine growth rate after a period of environmentally induced
      growth depression. Despite a focus on the implications of CG for aquaculture,
      little research has evaluated the effect of domesticated-wild hybridization on
      CG. Any deviation in the mean compensatory ability of hybrids relative to their
      wild progenitors, or any notable costs to compensation in terms of body
      morphology, could affect the ability of hybrids to persist in changing
      environments. We compared CG of farmed, wild and hybrid (F1, F2, wild backcross)
      juvenile Atlantic salmon (Salmo salar). Wild salmon experienced both lower
      routine and CG rates relative to farmed salmon, while hybrids were intermediate.
      However, the compensatory responses (slopes of the reaction norms) for each cross
      were parallel, indicating that hybridization did not affect the CG response
      itself. Morphological costs to compensation were not detected. In addition to
      contributing to risk assessments of the consequences of interbreeding between
      wild and escaped domesticated organisms, we conclude that plasticity studies on
      domesticated-wild hybrids and their progenitors are useful for testing basic
      predictions about the evolution of phenotypic plasticity, as well as
      understanding the evolutionary significance of hybrids. 

PMID- 25567995
TI  - Analysis of sustainable pest control using a pesticide and a screened refuge.
AB  - We describe and analyze a 'screened refuge' technique for indefinitely sustaining
      control of insect pests using transgenic pesticidal crops or an applied
      pesticide, even when resistance is not recessive. The screen is a physical
      barrier that restricts pest movement. In a deterministic discrete-time model of
      the use of this technique, we obtain asymptotic analytical formulas for the two
      important equilibria of the system in terms of the refuge size and the pest
      fitnesses, mutation rates, and mobility out of and into the refuge. One of the
      equilibria is stable and is the point at which the pest population is controlled.
      The other is a saddle whose stable manifold bounds the basin of attraction of the
      former: its location provides a measure of the tolerance of the control mechanism
      to perturbations in the resistant allele density. 

PMID- 25567996
TI  - Genetic structure, behaviour and invasion history of the Argentine ant
      supercolony in Australia.
AB  - Biological invasions have significant ecological, evolutionary and economic
      consequences. Ants are exemplary invaders and their invasion success is
      frequently attributed to a shift in social structure between native and
      introduced populations. Here, we use a multidisciplinary approach to determine
      the social structure, origin and expansion of the invasive Argentine ant,
      Linepithema humile, in Australia by linking behavioural and genetic studies with
      indicators of dispersal pathways and propagule pressure. Behavioural assays
      revealed a complete absence of aggression within and between three cities -
      Melbourne, Adelaide and Perth - spanning 2700 km across Australia. Microsatellite
      analyses showed intracity genetic homogeneity and limited but significant
      intercity genetic differentiation. Exceptions were two Perth nests that likely
      represent independent translocations from Adelaide. These patterns suggest
      efficient local gene flow with more limited jump dispersal via transport
      corridors between cities. Microsatellite analyses of L. humile from potential
      source regions, combined with data from port interceptions, trade pathways and
      the timeline of spread within Australia, implicate the main European supercolony
      as the source of L. humile in Melbourne. Such an introduction probably then
      redistributed across Australia and spread to New Zealand to form an expansive
      Australasian supercolony. 

PMID- 25567997
TI  - Competitive seedlings and inherited traits: a test of rapid evolution of Elymus
      multisetus (big squirreltail) in response to cheatgrass invasion.
AB  - Widespread invasion by Bromus tectorum (cheatgrass) in the Intermountain West has
      drastically altered native plant communities. We investigated whether Elymus
      multisetus (big squirreltail) is evolving in response to invasion and what traits
      contribute to increased performance. Seedlings from invaded areas exhibited
      significantly greater tolerance to B. tectorum competition and a greater ability
      to suppress B. tectorum biomass than seedlings from adjacent uninvaded areas. To
      identify potentially adaptive traits, we examined which phenological and
      phenotypic traits were correlated with seedling performance within the uninvaded
      area, determined their genetic variation by measuring sibling resemblance, and
      asked whether trait distribution had shifted in invaded areas. Increased
      tolerance to competition was correlated with early seedling root to shoot ratio,
      root fork number, and fine root length. Root forks differed among families, but
      none of these traits differed significantly across invasion status. Additionally,
      we surveyed more broadly for traits that varied between invaded and uninvaded
      areas. Elymus multisetus plants collected from invaded areas were smaller,
      allocated more biomass to roots, and produced a higher percentage of fine roots
      than plants from uninvaded areas. The ability of native populations to evolve in
      response to invasion has significant implications for the management and
      restoration of B. tectorum-invaded communities. 

PMID- 25567998
TI  - The origin and evolution of a recent agricultural weed: population genetic
      diversity of weedy populations of sunflower (Helianthus annuus L.) in Spain and
      France.
AB  - The recurrent evolution of crop-related weeds during agricultural history raises
      serious economic problems and challenging scientific questions. Weedy forms of
      sunflower, a species native from America, have been reported in European
      sunflower fields for a few decades. In order to understand their origin, we
      analysed the genetic diversity of a sample of weedy populations from France and
      Spain, and of conventional and ornamental varieties. A crop-specific maternally
      inherited marker was present in all weeds. At 16 microsatellite loci, the weedy
      populations shared most of their diversity with the conventional varieties. But
      they showed a large number of additional alleles absent from the cultivated pool.
      European weedy populations thus most probably originated from the unintentional
      pollination of maternal lines in seed production fields by wild plants growing
      nearby, resulting in the introduction of crop-wild hybrids into the farmers'
      fields. The wide diversity and the low population structure detected were
      indicative of a multiplicity of introductions events rather than of field-to
      field propagation. Further studies are required to understand the local
      evolutionary dynamics of a weedy population, and especially the respective roles
      of crop-to-weed gene flow and selection in the fate of an initial source of crop
      wild hybrids. 

PMID- 25567999
TI  - Ego depletion in color priming research: self-control strength moderates the
      detrimental effect of red on cognitive test performance.
AB  - Colors have been found to affect psychological functioning. Empirical evidence
      suggests that, in test situations, brief perceptions of the color red or even the
      word "red" printed in black ink prime implicit anxious responses and consequently
      impair cognitive performance. However, we propose that this red effect depends on
      people's momentary capacity to exert control over their prepotent responses
      (i.e., self-control). In three experiments (Ns = 66, 78, and 130), first
      participants' self-control strength was manipulated. Participants were then
      primed with the color or word red versus gray prior to completing an arithmetic
      test or an intelligence test. As expected, self-control strength moderated the
      red effect. While red had a detrimental effect on performance of participants
      with depleted self-control strength (ego depletion), it did not affect
      performance of participants with intact self-control strength. We discuss
      implications of the present findings within the current debate on the robustness
      of priming results. 

PMID- 25568000
TI  - Shared perceptions: morality is embedded in social contexts.
AB  - Morality helps make social life possible, but social life is embedded in many
      social contexts. Research on morality has generally neglected this and instead
      has emphasized people's general beliefs. We therefore investigated the extent to
      which different moral principles are perceived as embedded in social contexts. We
      conducted two studies investigating how diverse social contexts influence beliefs
      about the operative moral principles in distinct group types. Study 1 examined
      these perceptions using a within-subjects design, whereas Study 2 utilized a
      between-subjects design. We found a high degree of consensus among raters
      concerning the operative moral principles in groups, and each group type was
      characterized by a qualitatively distinct pattern of applicable moral principles.
      Political orientation, a focus of past research on morality, had a small
      influence on beliefs about operative moral principles. The implications of these
      findings for our understanding of morality and its functional role in groups are
      discussed. 

PMID- 25568001
TI  - Consultation of traditional bone setters instead of doctors: is it a
      sociocultural and educational or social insurance problem?
AB  - BACKGROUND: Patients consulting bone setters is common in the eastern and south
      eastern regions of Turkey. The reasons for consulting bone setters instead of
      qualified doctors remains unclear. We investigated the characteristics of such
      patients who consult traditional bone setters after trauma prior to admission to
      hospital. METHODS: In the study, 3,422 of 14,080 patients were investigated
      admitted to hospital between January 2012 and February 2013 with trauma or
      sequelae of such who were previously treated by bone setters. The characteristics
      of these patients and the main reasons for consultation of bone setters instead
      of doctors were recorded. RESULTS: Most of the patients consulting bone setters
      were found to be young adults or children. Generally speaking, the poorly
      educated prefer bone setters despite having social insurance. The most common
      reason (29.3%) was a general preference and secondarily (27.1%) the fear of being
      disabled after medical treatment. However, the most common cause of patients'
      consultation at hospital subsequently was due to complications of treatment
      (46.8%); indeed the complication rate after bone setters' intervention was found
      to be 54.8%. CONCLUSION: Although improvements have occurred in the access to and
      utilisation of healthcare services, consultation by patients of bone setters
      seems to be a sociocultural and educational issue rather than a problem of lack
      of medical insurance.

PMID- 25568002
TI  - An integrated genetic-demographic model to unravel the origin of genetic
      structure in European eel (Anguilla anguilla L.).
AB  - The evolutionary enlightened management of species with complex life cycles often
      requires the development of mathematical models integrating demographic and
      genetic data. The genetic structure of the endangered European eel (Anguilla
      anguilla L.) has been thoroughly analyzed in several studies in the past years.
      However, the interpretation of the key demographic and biologic processes that
      determine the observed spatio-temporal genetic structure has been very
      challenging owing to the complex life cycle of this catadromous species. Here, we
      present the first integrated demographic-genetic model applied to the European
      eel that explicitly accounts for different levels of larval and adult mixing
      during oceanic migrations and allows us to explore alternative hypotheses on
      genetic differentiation. Our analyses show that (i) very low levels of mixing
      occurring during larval dispersal or adult migration are sufficient to erase
      entirely any genetic differences among sub-populations; (ii) small-scale temporal
      differentiation in recruitment can arise if the spawning stock is subdivided in
      distinct reproductive groups; and (iii) the geographic differentiation component
      might be overestimated if a limited number of temporal recruits are analyzed. Our
      study can inspire the scientific debate on the interpretation of genetic
      structure in other species characterized by complex life cycle and long-range
      migrations. 

PMID- 25568003
TI  - Costs and benefits of thermal acclimation for codling moth, Cydia pomonella
      (Lepidoptera: Tortricidae): implications for pest control and the sterile insect
      release programme.
AB  - Sterile insect release (SIR) is used to suppress insect pest populations in agro
      ecosystems, but its success hinges on the performance of the released insects and
      prevailing environmental conditions. For example, low temperatures dramatically
      reduce SIR efficacy in cooler conditions. Here, we report on the costs and
      benefits of thermal acclimation for laboratory and field responses of codling
      moth, Cydia pomonella. Using a component of field fitness, we demonstrate that
      low temperature acclimated laboratory-reared moths are recaptured significantly
      more (~2-4*) under cooler conditions in the wild relative to warm-acclimated or
      control moths. However, improvements in low temperature performance in cold
      acclimated moths came at a cost to performance under warmer conditions. At high
      ambient temperatures, warm-acclimation improved field performance relative to
      control or cold-acclimated moths. Laboratory assessments of thermal activity and
      their limits matched the field results, indicating that these laboratory assays
      may be transferable to field performance. This study demonstrates clear costs and
      benefits of thermal acclimation on laboratory and field performance and the
      potential utility of thermal pretreatments for offsetting negative efficacy in
      SIR programmes under adverse thermal conditions. Consequently, the present work
      shows that evolutionary principles of phenotypic plasticity can be used to
      improve field performance and thus possibly enhance pest control programmes
      seeking increased efficacy. 

PMID- 25568004
TI  - Human-aided dispersal has altered but not erased the phylogeography of the tench.
AB  - Human-aided dispersal can result in phylogeographic patterns that do not reflect
      natural historical processes, particularly in species prone to intentional
      translocations by humans. Here, we use a multiple-gene sequencing approach to
      assess the effects of human-aided dispersal on phylogeography of the tench Tinca
      tinca, a widespread Eurasian freshwater fish with a long history in aquaculture.
      Spatial genetic analysis applied to sequence data from four unlinked loci and 67
      geographic localities (38-382 gene copies per locus) defined two groups of
      populations that were little structured geographically but were significantly
      differentiated from each other, and it identified locations of major genetic
      breaks, which were concordant across genes and were driven by distributions of
      two phylogroups. This pattern most reasonably reflects isolation in two major
      glacial refugia and subsequent range expansions, with the Eastern and Western
      phylogroups remaining largely allopatric throughout the tench range. However,
      this phylogeographic variation was also present in all 17 cultured breeds
      studied, and some populations at the western edge of the native range contained
      the Eastern phylogroup. Thus, natural processes have played an important role in
      structuring tench populations, but human-aided dispersal has also contributed
      significantly, with the admixed genetic composition of cultured breeds most
      likely contributing to the introgression. 

PMID- 25568005
TI  - Historical changes in genotypic frequencies at the Pantophysin locus in Atlantic
      cod (Gadus morhua) in Icelandic waters: evidence of fisheries-induced selection?
AB  - The intense fishing mortality imposed on Atlantic cod in Icelandic waters during
      recent decades has resulted in marked changes in stock abundance, as well as in
      age and size composition. Using a molecular marker known to be under selection
      (Pan I) along with a suite of six neutral microsatellite loci, we analysed an
      archived data set and revealed evidence of distinct temporal changes in the
      frequencies of genotypes at the Pan I locus among spawning Icelandic cod,
      collected between 1948 and 2002, a period characterized by high fishing pressure.
      Concurrently, temporal stability in the composition of the microsatellite loci
      was established within the same data set. The frequency of the Pan I(BB) genotype
      decreased over a period of six decades, concomitant with considerable spatial and
      technical changes in fishing effort that resulted in the disappearance of older
      individuals from the fishable stock. Consequently, these changes have likely led
      to a change in the genotype frequencies at this locus in the spawning stock of
      Icelandic cod. The study highlights the value of molecular genetic approaches
      that combine functional and neutral markers examined in the same set of
      individuals for investigations of the selective effects of harvesting and
      reiterates the need for an evolutionary dimension to fisheries management. 

PMID- 25568006
TI  - Genetic factors associated with population size may increase extinction risks and
      decrease colonization potential in a keystone tropical pine.
AB  - Pioneer species are essential for forest regeneration and ecosystem resilience.
      Pinus chiapensis is an endangered pioneer key species for tropical montane cloud
      forest regeneration in Mesoamerica. Human activities have severely reduced some
      P. chiapensis populations, which exhibited a small or null colonization potential
      suggesting the involvement of genetic factors associated with small populations.
      We explored the relationships between (i) population genetic diversity
      (allozymes) and population size, including sampling size effects, (ii) fitness
      estimates associated with colonization potential (seed viability and seedling
      performance) in a common environment and population size, and (iii) fitness
      estimates and observed heterozygosity in populations with sizes spanning five
      orders of magnitude. All the estimates of genetic diversity and fitness increased
      significantly with population size. Low fitness was detected in progenies of
      small populations of disturbed and undisturbed habitats. Progenies with the
      lowest observed heterozygosity displayed the lowest fitness estimates, which, in
      turn, increased with heterozygosity, but seed viability peaked at intermediate
      heterozygosity values suggesting inbreeding and outbreeding depression.
      Inbreeding depression appears to be the most immediate genetic factor in
      population decline. Conservation efforts should try to maintain large and
      genetically diverse populations, enhance gene flow by restoring connectivity
      between adjacent populations, and avoid genetically distant individuals. 

PMID- 25568007
TI  - The role of anthropogenic vs. natural in-stream structures in determining
      connectivity and genetic diversity in an endangered freshwater fish, Macquarie
      perch (Macquaria australasica).
AB  - Habitat fragmentation is one of the leading causes of population declines,
      threatening ecosystems worldwide. Freshwater taxa may be particularly sensitive
      to habitat loss as connectivity between suitable patches of habitat is restricted
      not only by the natural stream network but also by anthropogenic factors. Using a
      landscape genetics approach, we assessed the impact of habitat availability on
      population genetic diversity and connectivity of an endangered Australian
      freshwater fish Macquarie perch, Macquaria australasica (Percichthyidae). The
      relative contribution of anthropogenic versus natural in-stream habitat
      structures in shaping genetic structure and diversity in M. australasica was
      quite striking. Genetic diversity was significantly higher in locations with a
      higher river slope, a correlate of the species preferred habitat - riffles. On
      the other hand, barriers degrade preferred habitat and impede dispersal,
      contributing to the degree of genetic differentiation among populations. Our
      results highlight the importance of landscape genetics to understanding the
      environmental factors affecting freshwater fish populations and the potential
      practical application of this approach to conservation management of other
      freshwater organisms. 

PMID- 25568008
TI  - Maintenance of phenotypic variation: repeatability, heritability and size
      dependent processes in a wild brook trout population.
AB  - Phenotypic variation in body size can result from within-cohort variation in
      birth dates, among-individual growth variation and size-selective processes. We
      explore the relative effects of these processes on the maintenance of wide
      observed body size variation in stream-dwelling brook trout (Salvelinus
      fontinalis). Based on the analyses of multiple recaptures of individual fish, it
      appears that size distributions are largely determined by the maintenance of
      early size variation. We found no evidence for size-dependent compensatory growth
      (which would reduce size variation) and found no indication that size-dependent
      survival substantially influenced body size distributions. Depensatory growth
      (faster growth by larger individuals) reinforced early size variation, but was
      relatively strong only during the first sampling interval (age-0, fall). Maternal
      decisions on the timing and location of spawning could have a major influence on
      early, and as our results suggest, later (>age-0) size distributions. If this is
      the case, our estimates of heritability of body size (body length = 0.25) will be
      dominated by processes that generate and maintain early size differences. As a
      result, evolutionary responses to environmental change that are mediated by body
      size may be largely expressed via changes in the timing and location of
      reproduction. 

PMID- 25568009
TI  - Evolutionary applications summer 2011.

PMID- 25568010
TI  - Genetic correlations between adults and larvae in a marine fish: potential
      effects of fishery selection on population replenishment.
AB  - Correlated genetic responses have been hypothesized as important components of
      fishery-induced evolution, although predictive data from wild populations have
      been difficult to obtain. Here, we demonstrate substantial genetic correlations
      between a trait often subjected to fishery selection (adult body length) and
      traits that affect survival of larvae (length and swimming performance) in a wild
      population of a marine fish (bicolor damselfish, Stegastes partitus). Through
      both genetic covariance and size-dependent maternal effects, selection on adult
      size may cause a considerable, correlated response in larval traits. To quantify
      how variation in larval traits may affect survival, we introduce a flexible
      method that uses information from selection measurements to account for frequency
      dependence and estimate the relationship between phenotype and relative survival
      across a broad range of phenotypic values. Using this method, we synthesize
      studies of selective mortality on larval size for eight species of fish and show
      that variation in larval size may result in considerable variation in larval
      survival. We predict that observed rates of fishery selection on adult marine
      fishes may substantially reduce larval size and survival. The evolution of
      smaller larvae in response to fishery selection may therefore have substantial
      consequences for the viability of fished populations. 

PMID- 25568011
TI  - Relative risks of inbreeding and outbreeding depression in the wild in endangered
      salmon.
AB  - Conservation biologists routinely face the dilemma of keeping small, fragmented
      populations isolated, wherein inbreeding depression may ensue, or mixing such
      populations, which may exacerbate population declines via outbreeding depression.
      The joint evaluation of inbreeding and outbreeding risks in the wild cannot be
      readily conducted in endangered species, so a suggested 'safe' strategy is to mix
      ecologically and genetically similar populations. To evaluate this strategy, we
      carried out a reciprocal transplant experiment involving three neighboring
      populations of endangered Atlantic salmon (Salmo salar) now bred in captivity and
      maintained in captive and wild environments. Pure, inbred, and outbred (first and
      second generation) cross types were released and recaptured in the wild to
      simultaneously test for local adaptation, inbreeding depression, and outbreeding
      depression. We found little evidence of inbreeding depression after one
      generation of inbreeding and little evidence of either heterosis or outbreeding
      depression via genetic incompatibilities after one or two generations of
      outbreeding. A trend for outbreeding depression via the loss of local adaptation
      was documented in one of three populations. The effects of inbreeding were not
      significantly different from the effects of outbreeding. Hence, at the geographic
      scale evaluated (34-50 km), inbreeding for one generation and outbreeding over
      two generations may have similar effects on the persistence of small populations.
      The results further suggested that outbreeding outcomes may be highly variable or
      unpredictable at small genetic distances. Our work highlights the necessity of
      evaluating the relative costs of inbreeding and outbreeding in the conservation
      and management of endangered species on a case-by-case basis. 

PMID- 25568012
TI  - Locus-dependent selection in crop-wild hybrids of lettuce under field conditions
      and its implication for GM crop development.
AB  - Gene escape from crops has gained much attention in the last two decades, as
      transgenes introgressing into wild populations could affect the latter's
      ecological characteristics. However, different genes have different likelihoods
      of introgression. The mixture of selective forces provided by natural conditions
      creates an adaptive mosaic of alleles from both parental species. We investigated
      segregation patterns after hybridization between lettuce (Lactuca sativa) and its
      wild relative, L. serriola. Three generations of hybrids (S1, BC1, and BC1S1)
      were grown in habitats mimicking the wild parent's habitat. As control, we
      harvested S1 seedlings grown under controlled conditions, providing very limited
      possibility for selection. We used 89 AFLP loci, as well as more recently
      developed dominant markers, 115 retrotransposon markers (SSAP), and 28 NBS loci
      linked to resistance genes. For many loci, allele frequencies were biased in
      plants exposed to natural field conditions, including over-representation of crop
      alleles for various loci. Furthermore, Linkage disequilibrium was locally
      changed, allegedly by selection caused by the natural field conditions, providing
      ample opportunity for genetic hitchhiking. Our study indicates that when
      developing genetically modified crops, a judicious selection of insertion sites,
      based on knowledge of selective (dis)advantages of the surrounding crop genome
      under field conditions, could diminish transgene persistence. 

PMID- 25568013
TI  - Winning the invasion roulette: escapes from fish farms increase admixture and
      facilitate establishment of non-native rainbow trout.
AB  - Aquaculture is a major source of invasive aquatic species, despite the fact that
      cultured organisms often have low genetic diversity and tend to be maladapted to
      survive in the wild. Yet, to what extent aquaculture escapees become established
      by means of high propagule pressure and multiple origins is not clear. We
      analysed the genetic diversity of 15 established populations and four farmed
      stocks of non-native rainbow trout in Chile, a species first introduced for
      recreational fishing around 1900, but which has in recent decades escaped in
      large numbers from fish farms and become widespread. Aquaculture propagule
      pressure was a good predictor of the incidence of farm escapees, which
      represented 16% of all free-ranging rainbow trout and were present in 80% of the
      study rivers. Hybrids between farm escapes and established trout were present in
      all rivers at frequencies ranging between 7 and 69%, and population admixture was
      positively correlated with genetic diversity. We suggest that non-native
      salmonids introduced into the Southern Hemisphere could benefit from admixture
      because local adaptations may not have yet developed, and there may be initially
      little fitness loss resulting from outbreeding depression. 

PMID- 25568014
TI  - Transgenes for insect resistance reduce herbivory and enhance fecundity in
      advanced generations of crop-weed hybrids of rice.
AB  - Gene flow from transgenic crops allows novel traits to spread to sexually
      compatible weeds. Traits such as resistance to insects may enhance the fitness of
      weeds, but few studies have tested for these effects under natural field
      conditions. We created F 2 and F 3 crop-weed hybrid lineages of genetically
      engineered rice (Oryza sativa) using lines with two transgene constructs, cowpea
      trypsin inhibitor (CpTI) and a Bt transgene linked to CpTI (Bt/CpTI). Experiments
      conducted in Fuzhou, China, demonstrated that CpTI alone did not significantly
      affect fecundity, although it reduced herbivory. In contrast, under certain
      conditions, Bt/CpTI conferred up to 79% less insect damage and 47% greater
      fecundity relative to nontransgenic controls, and a 44% increase in fecundity
      relative to the weedy parent. A small fitness cost was detected in F 3 progeny
      with Bt/CpTI when grown under low insect pressure and direct competition with
      transgene-negative controls. We conclude that Bt/CpTI transgenes may introgress
      into co-occurring weedy rice populations and contribute to greater seed
      production when target insects are abundant. However, the net fitness benefits
      that are associated with Bt/CpTI could be ephemeral if insect pressure is
      lacking, for example, because of widespread planting of Bt cultivars that
      suppress target insect populations. 

PMID- 25568015
TI  - Gene flow between wheat and wild relatives: empirical evidence from Aegilops
      geniculata, Ae. neglecta and Ae. triuncialis.
AB  - Gene flow between domesticated species and their wild relatives is receiving
      growing attention. This study addressed introgression between wheat and natural
      populations of its wild relatives (Aegilops species). The sampling included 472
      individuals, collected from 32 Mediterranean populations of three widespread
      Aegilops species (Aegilops geniculata, Ae. neglecta and Ae. triuncialis) and
      compared wheat field borders to areas isolated from agriculture. Individuals were
      characterized with amplified fragment length polymorphism fingerprinting,
      analysed through two computational approaches (i.e. Bayesian estimations of
      admixture and fuzzy clustering), and sequences marking wheat-specific insertions
      of transposable elements. With this combined approach, we detected substantial
      gene flow between wheat and Aegilops species. Specifically, Ae. neglecta and Ae.
      triuncialis showed significantly more admixed individuals close to wheat fields
      than in locations isolated from agriculture. In contrast, little evidence of gene
      flow was found in Ae. geniculata. Our results indicated that reproductive
      barriers have been regularly bypassed during the long history of sympatry between
      wheat and Aegilops. 

PMID- 25568016
TI  - Context-dependent effects of induced resistance under co-infection in a plant
      pathogen interaction.
AB  - The ability of a parasite strain to establish and grow on its host may be
      drastically altered by simultaneous infection by other parasite strains, and
      dynamics under multiple infection have been suggested to be a major force driving
      pathogen evolution. Here, I studied whether hosts' induced defenses mediate
      dynamics of multiple infection of the fungal pathogen, Podosphaera plantaginis,
      infecting Plantago lanceolata. A laboratory study of sequential infections, where
      interaction between pathogen strains was prevented, showed that ability to
      establish remained unaffected, but prior infection elevates the host's resistance
      to the degree that subsequent infection development is significantly reduced.
      However, when inoculated plants and their healthy controls were planted back into
      their natural populations, hosts with prior infection became more heavily
      infected by the subsequent infections than the initially healthy plants. Hence, a
      controlled short-term laboratory study is a poor predictor of the host's ability
      to mediate multiple infection during the course of natural epidemics. These
      results have applied implications for priming where the plants' defenses are
      elicited to provide protection against further attack, highlighting the
      importance of testing priming under natural conditions for relevant time scales. 

PMID- 25568018
TI  - Comparing the genetic architecture and potential response to selection of
      invasive and native populations of reed canary grass.
AB  - Evolutionary processes such as migration, genetic drift, and natural selection
      are thought to play a prominent role in species invasions into novel
      environments. However, few empirical studies have explored the mechanistic basis
      of invasion in an evolutionary framework. One promising tool for inferring
      evolutionarily important changes in introduced populations is the genetic
      variance-covariance matrix (G matrix). G matrix comparisons allow for the
      inference of changes in the genetic architecture of introduced populations
      relative to their native counterparts that may facilitate invasion. Here, we
      compare the G matrices of reed canary grass (Phalaris arundinacea L.) populations
      across native and invasive ranges, and between populations along a latitudinal
      gradient within each range. We find that the major differences in genetic
      architecture occur between populations at the Northern and Southern margins
      within each range, not between native and invasive populations. Previous studies
      have found that multiple introductions in introduced populations caused an
      increase in genetic variance on which selection could act. In addition, we find
      that differences in the evolutionary potential of Phalaris populations are driven
      by differences in latitude, suggesting that selection also shapes the
      evolutionary trajectory of invasive populations. 

PMID- 25568019
TI  - Reproductive performance of alternative male phenotypes of growth hormone
      transgenic Atlantic salmon (Salmo salar).
AB  - Growth hormone (GH) transgenic Atlantic salmon (Salmo salar) is one of the first
      transgenic animals being considered for commercial farming, yet ecological and
      genetic concerns remain should they enter the wild and interact reproductively
      with wild fish. Here, we provide the first empirical data reporting on the
      breeding performance of GH transgenic Atlantic salmon males, including that of an
      alternative male reproductive phenotype (i.e. small, precocially mature parr), in
      pair-wise competitive trials within a naturalised stream mesocosm. Wild
      anadromous (i.e. large, migratory) males outperformed captively reared transgenic
      counterparts in terms of nest fidelity, quivering frequency and spawn
      participation. Similarly, despite displaying less aggression, captively reared
      nontransgenic mature parr were superior competitors to their transgenic
      counterparts in terms of nest fidelity and spawn participation. Moreover,
      nontransgenic parr had higher overall fertilisation success than transgenic parr,
      and their offspring were represented in more spawning trials. Although transgenic
      males displayed reduced breeding performance relative to nontransgenics, both
      male reproductive phenotypes demonstrated the ability to participate in natural
      spawning events and thus have the potential to contribute genes to subsequent
      generations. 

PMID- 25568020
TI  - Varying disease-mediated selection at different life-history stages of Atlantic
      salmon in fresh water.
AB  - Laboratory studies on associations between disease resistance and susceptibility
      and major histocompatibility (MH) genes in Atlantic salmon Salmo salar have shown
      the importance of immunogenetics in understanding the capacity of populations to
      fight specific diseases. However, the occurrence and virulence of pathogens may
      vary spatially and temporally in the wild, making it more complicated to predict
      the overall effect that MH genes exert on fitness of natural populations and over
      several life-history stages. Here we show that MH variability is a significant
      determinant of salmon survival in fresh water, by comparing observed and expected
      genotype frequencies at MH and control microsatellite loci at parr and migrant
      stages in the wild. We found that additive allelic effects at immunogenetic loci
      were more likely to determine survival than dominance deviation, and that
      selection on certain MH alleles varied with life stage, possibly owing to varying
      pathogen prevalence and/or virulence over time. Our results highlight the
      importance of preserving genetic diversity (particularly at MH loci) in wild
      populations, so that they have the best chance of adapting to new and increased
      disease challenges as a result of projected climate warming and increasing
      aquaculture. 

PMID- 25568021
TI  - Little impact of hatchery supplementation that uses native broodstock on the
      genetic structure and diversity of steelhead trout revealed by a large-scale
      spatio-temporal microsatellite survey.
AB  - Artificial breeding programs initiated to enhance the size of animal populations
      are often motivated by the desire to increase harvest opportunities. The
      introduction of non-native genotypes, however, can have negative evolutionary
      impacts. These may be direct, such as introgressive hybridization, or indirect
      via competition. Less is known about the effects of stocking with native
      genotypes. We assayed variation at nine microsatellite loci in 902 steelhead
      trout (Oncorhynchus mykiss) from five rivers in British Columbia, Canada. These
      samples were collected over 58 years, a time period that spanned the initiation
      of native steelhead trout broodstock hatchery supplementation in these rivers. We
      detected no changes in estimates of effective population size, genetic variation
      or temporal genetic structure within any population, nor of altered genetic
      structure among them. Genetic interactions with nonmigratory O. mykiss, the use
      of substantial numbers of primarily native broodstock with an approximate 1:1
      male-to-female ratio, and/or poor survival and reproductive success of hatchery
      fish may have minimized potential genetic changes. Although no genetic changes
      were detected, ecological effects of hatchery programs still may influence wild
      population productivity and abundance. Their effects await the design and
      implementation of a more comprehensive evaluation program. 

PMID- 25568022
TI  - The microsporidian parasite Vavraia culicis as a potential late life-acting
      control agent of malaria.
AB  - Microsporidian parasites are being considered as alternatives to conventional
      insecticides for malaria control. They should reduce malaria transmission by
      shortening the lifespan of female mosquitoes and thus killing them before they
      transmit malaria. As the parasite replicates throughout the mosquito's life, it
      should have little detrimental effects on young mosquitoes, thus putting less
      selection pressure on the hosts to evolve resistance. Here, we examined these
      expectations for the microsporidian Vavraia culicis on Anopheles gambiae Giles
      sensu stricto mosquitoes under varying environmental conditions. Infection by the
      microsporidian delayed pupation by 10%, decreased fecundity by 23% and reduced
      adult lifespan by 27%, with higher infectious doses causing greater effects. The
      decrease of lifespan was mostly because of an increase of the mortality rate with
      age. Similarly, the parasite's effect on mosquito fecundity increased with the
      mosquitoes' age. Neither infection nor food availability affected juvenile
      survival. Thus, as V. culicis reduced the longevity of A. gambiae (s.s.), yet
      affected mortality and fecundity of the young mosquitoes only slightly, the
      microsporidian is a promising alternative to insecticides for effective malaria
      control that will impose little evolutionary pressure for resistance. 

PMID- 25568023
TI  - Anthropogenic habitat alteration induces rapid morphological divergence in a
      native stream fish.
AB  - Anthropogenic habitat alteration creates novel environments that can alter
      selection pressures. Construction of reservoirs worldwide has disturbed riverine
      ecosystems by altering biotic and abiotic environments of impounded streams.
      Changes to fish communities in impoundments are well documented, but effects of
      those changes on native species persisting in reservoirs, which are presumably
      subjected to novel selective pressures, are largely unexplored. I assessed body
      shape variation of a native stream fish in reservoir habitats and streams from
      seven reservoir basins in the Central Plains of the USA. Body shape significantly
      and consistently diverged in reservoirs compared with stream habitats within
      reservoir basins; individuals from reservoir populations were deeper-bodied and
      had smaller heads compared with stream populations. Individuals from reservoir
      habitats also exhibited lower overall shape variation compared with stream
      individuals. I assessed the contribution of genotypic divergence and predator
      induced phenotypic plasticity on body shape variation by rearing offspring from a
      reservoir and a stream population with or without a piscivorous fish. Significant
      population-level differences in body shape persisted in offspring, and both
      populations demonstrated similar predator-induced phenotypic plasticity. My
      results suggest that, although components of body shape are plastic,
      anthropogenic habitat modification may drive trait divergence in native fish
      populations in reservoir-altered habitats. 

PMID- 25568024
TI  - Evolutionary Applications open to all.

PMID- 25568025
TI  - Evolution of plant-pollinator mutualisms in response to climate change.
AB  - Climate change has the potential to desynchronize the phenologies of
      interdependent species, with potentially catastrophic effects on mutualist
      populations. Phenologies can evolve, but the role of evolution in the response of
      mutualisms to climate change is poorly understood. We developed a model that
      explicitly considers both the evolution and the population dynamics of a plant
      pollinator mutualism under climate change. How the populations evolve, and thus
      whether the populations and the mutualism persist, depends not only on the rate
      of climate change but also on the densities and phenologies of other species in
      the community. Abundant alternative mutualist partners with broad temporal
      distributions can make a mutualism more robust to climate change, while abundant
      alternative partners with narrow temporal distributions can make a mutualism less
      robust. How community composition and the rate of climate change affect the
      persistence of mutualisms is mediated by two-species Allee thresholds.
      Understanding these thresholds will help researchers to identify those mutualisms
      at highest risk owing to climate change. 

PMID- 25568026
TI  - Hybridization and invasion: an experimental test with diffuse knapweed (Centaurea
      diffusa Lam.).
AB  - A number of studies have suggested a link between hybridization and invasion. In
      this study, we experimentally test the potential for hybridization to influence
      invasion through a greenhouse common garden study. Diffuse knapweed (DK)
      (Centaurea diffusa Lam.) was introduced to North America with admixture from
      spotted knapweed (SK) (Centaurea stoebe subsp. stoebe L.). Comparisons between
      North American DK (including hybrid phenotypes) and native (European) DK in a
      common garden did not reveal enhanced performance or increased phenotypic
      variance, suggesting that pre-introduction hybridization or, more generally, post
      introduction evolutionary change has not significantly contributed to the
      invasion of DK. In contrast, early generation hybrids [artificially created
      Backcross 1 (BC1) plants] exhibited increased variance for eight of the examined
      traits, and greater leaf and reproductive shoot production when compared to North
      American DK. Individual BC1 lines differed for several traits, suggesting the
      importance of the cross for drawing conclusions from such comparisons. When
      compared to the parental species (DK and SK), the BC1 plants were not
      transgressive for any of the measured traits. Overall, these findings suggest
      that if diploid SK is introduced to North America, interspecific hybridization
      has the potential to result in even more aggressive invaders. 

PMID- 25568027
TI  - Interspecific hybridization transfers a previously unknown glyphosate resistance
      mechanism in Amaranthus species.
AB  - A previously unknown glyphosate resistance mechanism, amplification of the 5
      enolpyruvyl shikimate-3-phosphate synthase gene, was recently reported in
      Amaranthus palmeri. This evolved mechanism could introgress to other weedy
      Amaranthus species through interspecific hybridization, representing an avenue
      for acquisition of a novel adaptive trait. The objective of this study was to
      evaluate the potential for this glyphosate resistance trait to transfer via
      pollen from A. palmeri to five other weedy Amaranthus species (Amaranthus
      hybridus, Amaranthus powellii, Amaranthus retroflexus, Amaranthus spinosus, and
      Amaranthus tuberculatus). Field and greenhouse crosses were conducted using
      glyphosate-resistant male A. palmeri as pollen donors and the other Amaranthus
      species as pollen recipients. Hybridization between A. palmeri and A. spinosus
      occurred with frequencies in the field studies ranging from <0.01% to 0.4%, and
      1.4% in greenhouse crosses. A majority of the A. spinosus * A. palmeri hybrids
      grown to flowering were monoecious and produced viable seed. Hybridization
      occurred in the field study between A. palmeri and A. tuberculatus (<0.2%), and
      between A. palmeri and A. hybridus (<0.01%). This is the first documentation of
      hybridization between A. palmeri and both A. spinosus and A. hybridus. 

PMID- 25568028
TI  - Detection of outlier loci and their utility for fisheries management.
AB  - Genetics-based approaches have informed fisheries management for decades, yet
      remain challenging to implement within systems involving recently diverged stocks
      or where gene flow persists. In such cases, genetic markers exhibiting locus
      specific ('outlier') effects associated with divergent selection may provide
      promising alternatives to loci that reflect genome-wide ('neutral') effects for
      guiding fisheries management. Okanagan Lake kokanee (Oncorhynchus nerka), a
      fishery of conservation concern, exhibits two sympatric ecotypes adapted to
      different reproductive environments; however, previous research demonstrated the
      limited utility of neutral microsatellites for assigning individuals. Here, we
      investigated the efficacy of an outlier-based approach to fisheries management by
      screening >11 000 expressed sequence tags for linked microsatellites and
      conducting genomic scans for kokanee sampled across seven spawning sites. We
      identified eight outliers among 52 polymorphic loci that detected ecotype-level
      divergence, whereas there was no evidence of divergence at neutral loci. Outlier
      loci exhibited the highest self-assignment accuracy to ecotype (92.1%),
      substantially outperforming 44 neutral loci (71.8%). Results were robust among
      sampling years, with assignment and mixed composition estimates for individuals
      sampled in 2010 mirroring baseline results. Overall, outlier loci constitute
      promising alternatives for informing fisheries management involving recently
      diverged stocks, with potential applications for designating management units
      across a broad range of taxa. 

PMID- 25568029
TI  - Assessing the role of non-cotton refuges in delaying Helicoverpa armigera
      resistance to Bt cotton in West Africa.
AB  - Non-cotton host plants without Bacillus thuringiensis (Bt) toxins can provide
      refuges that delay resistance to Bt cotton in polyphagous insect pests. It has
      proven difficult, however, to determine the effective contribution of such
      refuges and their role in delaying resistance evolution. Here, we used
      biogeochemical markers to quantify movement of Helicoverpa armigera moths from
      non-cotton hosts to cotton fields in three agricultural landscapes of the West
      African cotton belt (Cameroon) where Bt cotton was absent. We show that the
      contribution of non-cotton hosts as a source of moths was spatially and
      temporally variable, but at least equivalent to a 7.5% sprayed refuge of non-Bt
      cotton. Simulation models incorporating H. armigera biological parameters,
      however, indicate that planting non-Bt cotton refuges may be needed to
      significantly delay resistance to cotton producing the toxins Cry1Ac and Cry2Ab.
      Specifically, when the concentration of one toxin (here Cry1Ac) declined
      seasonally, resistance to Bt cotton often occurred rapidly in simulations where
      refuges of non-Bt cotton were rare and resistance to Cry2Ab was non-recessive,
      because resistance was essentially driven by one toxin (here Cry2Ab). The use of
      biogeochemical markers to quantify insect movement can provide a valuable tool to
      evaluate the role of non-cotton refuges in delaying the evolution of H. armigera
      resistance to Bt cotton. 

PMID- 25568030
TI  - Development on drought-stressed host plants affects life history, flight
      morphology and reproductive output relative to landscape structure.
AB  - With global climate change, rainfall is becoming more variable. Predicting the
      responses of species to changing rainfall levels is difficult because, for
      example in herbivorous species, these effects may be mediated indirectly through
      changes in host plant quality. Furthermore, species responses may result from a
      simultaneous interaction between rainfall levels and other environmental
      variables such as anthropogenic land use or habitat quality. In this eco
      evolutionary study, we examined how male and female Pararge aegeria (L.) from
      woodland and agricultural landscape populations were affected by the development
      on drought-stressed host plants. Compared with individuals from woodland
      landscapes, when reared on drought-stressed plants agricultural individuals had
      longer development times, reduced survival rates and lower adult body masses.
      Across both landscape types, growth on drought-stressed plants resulted in males
      and females with low forewing aspect ratios and in females with lower wing
      loading and reduced fecundity. Development on drought-stressed plants also had a
      landscape-specific effect on reproductive output; agricultural females laid eggs
      that had a significantly lower hatching success. Overall, our results highlight
      several potential mechanisms by which low water availability, via changes in host
      plant quality, may differentially influence P. aegeria populations relative to
      landscape structure. 

PMID- 25568031
TI  - Introgression of domesticated alleles into a wild trout genotype and the impact
      on seasonal survival in natural lakes.
AB  - We tested the fitness consequences of introgression of fast-growing domesticated
      fish into a wild population. Fry from wild and domesticated rainbow trout
      (Oncorhynchus mykiss) crosses, F1 hybrids, and first- and second-generation
      backcrosses were released into two natural lakes. Parentage analysis using
      microsatellite loci facilitated the identification of survivors, so fitness was
      estimated in nature from the first-feeding stage. Results indicated that under
      certain conditions, domesticated fish survived at least as well as wild fish
      within the same environment. Relative growth and survival of the crosses,
      however, were highly dependent on environment. During the first summer, fastest
      growing crosses had the highest survival, but this trend was reversed after one
      winter and another summer. Although the F1 hybrids showed evidence of outbreeding
      depression because of the disruption of local adaptation, there was little
      evidence of outbreeding depression in the backcrosses, and the second-generation
      backcrosses exhibited a wild-type phenotype. This information is relevant for
      assessing the multigenerational risk of escaped or released domesticated fish
      should they successfully interbreed with wild populations and provides
      information on how to minimize detrimental impacts of a conservation breeding
      and/or management programme. These data also further understanding of the
      selection pressures in nature that maintain submaximal rates of growth. 

PMID- 25568033
TI  - Evolution and Biodiversity: the evolutionary basis of biodiversity and its
      potential for adaptation to global change.

PMID- 25568032
TI  - Anthropogenically induced adaptation to invade (AIAI): contemporary adaptation to
      human-altered habitats within the native range can promote invasions.
AB  - Adaptive evolution is currently accepted as playing a significant role in
      biological invasions. Adaptations relevant to invasions are typically thought to
      occur either recently within the introduced range, as an evolutionary response to
      novel selection regimes, or within the native range, because of long-term
      adaptation to the local environment. We propose that recent adaptation within the
      native range, in particular adaptations to human-altered habitat, could also
      contribute to the evolution of invasive populations. Populations adapted to human
      altered habitats in the native range are likely to increase in abundance within
      areas frequented by humans and associated with human transport mechanisms, thus
      enhancing the likelihood of transport to a novel range. Given that habitats are
      altered by humans in similar ways worldwide, as evidenced by global environmental
      homogenization, propagules from populations adapted to human-altered habitats in
      the native range should perform well within similarly human-altered habitats in
      the novel range. We label this scenario 'Anthropogenically Induced Adaptation to
      Invade'. We illustrate how it differs from other evolutionary processes that may
      occur during invasions, and how it can help explain accelerating rates of
      invasions. 

PMID- 25568034
TI  - Invasive species as drivers of evolutionary change: cane toads in tropical
      Australia.
AB  - The arrival of an invasive species can have wide-ranging ecological impacts on
      native taxa, inducing rapid evolutionary responses in ways that either reduce the
      invader's impact or exploit the novel opportunity that it provides. The invasion
      process itself can cause substantial evolutionary shifts in traits that influence
      the invader's dispersal rate (via both adaptive and non-adaptive mechanisms) and
      its ability to establish new populations. I briefly review the nature of
      evolutionary changes likely to be set in train by a biological invasion, with
      special emphasis on recent results from my own research group on the invasion of
      cane toads (Rhinella marina) through tropical Australia. The toads' invasion has
      caused evolutionary changes both in the toads and in native taxa. Many of those
      changes are adaptive, but others may result from non-adaptive evolutionary
      processes: for example, the evolved acceleration in toad dispersal rates may be
      due to spatial sorting of dispersal-enhancing genes, rather than fitness
      advantages to faster-dispersing individuals. Managers need to incorporate
      evolutionary dynamics into their conservation planning, because biological
      invasions can affect both the rates and the trajectories of evolutionary change. 

PMID- 25568035
TI  - Genetic erosion impedes adaptive responses to stressful environments.
AB  - Biodiversity is increasingly subjected to human-induced changes of the
      environment. To persist, populations continually have to adapt to these often
      stressful changes including pollution and climate change. Genetic erosion in
      small populations, owing to fragmentation of natural habitats, is expected to
      obstruct such adaptive responses: (i) genetic drift will cause a decrease in the
      level of adaptive genetic variation, thereby limiting evolutionary responses;
      (ii) inbreeding and the concomitant inbreeding depression will reduce individual
      fitness and, consequently, the tolerance of populations to environmental stress.
      Importantly, inbreeding generally increases the sensitivity of a population to
      stress, thereby increasing the amount of inbreeding depression. As adaptation to
      stress is most often accompanied by increased mortality (cost of selection), the
      increase in the 'cost of inbreeding' under stress is expected to severely hamper
      evolutionary adaptive processes. Inbreeding thus plays a pivotal role in this
      process and is expected to limit the probability of genetically eroded
      populations to successfully adapt to stressful environmental conditions.
      Consequently, the dynamics of small fragmented populations may differ
      considerably from large nonfragmented populations. The resilience of fragmented
      populations to changing and deteriorating environments is expected to be greatly
      decreased. Alleviating inbreeding depression, therefore, is crucial to ensure
      population persistence. 

PMID- 25568037
TI  - Changing organisms in rapidly changing anthropogenic landscapes: the significance
      of the 'Umwelt'-concept and functional habitat for animal conservation.
AB  - There is a growing recognition for the significance of evolutionary thinking in
      ecology and conservation biology. However, ecology and conservation studies often
      work with species-specific, fixed traits that ignore intraspecific variation. The
      way the habitat of a species is considered is an example of typological thinking
      biased by human perception. Structural habitat units (e.g., land cover types) as
      perceived by humans may not represent functional habitat units for other
      organisms. Human activity may also interfere with the environmental information
      used by organisms. Therefore, the Umwelt-concept from ethology needs to be
      integrated in the way we think about habitat and habitat selection. It states
      that different organisms live in different perceptual worlds dealing with
      specific subsamples of the environment as a result of their evolutionary and
      developmental history. The resource-based habitat concept is a functional habitat
      model based on resource distributions (consumables and conditions) and individual
      movements. This behavioural approach takes into account aspects that relate to
      the perceptual world of organisms. This approach may offer new opportunities for
      conservation and may help avoid failures with habitat restoration. Perceptual
      ability may be subject to adaptive change, but it may also constrain organisms
      from showing adaptive behaviours in rapidly changing environments. 

PMID- 25568036
TI  - Genomic toolboxes for conservation biologists.
AB  - Conservation genetics is expanding its research horizon with a genomic approach,
      by incorporating the modern techniques of next-generation sequencing (NGS).
      Application of NGS overcomes many limitations of conservation genetics. First,
      NGS allows for genome-wide screening of markers, which may lead to a more
      representative estimation of genetic variation within and between populations.
      Second, NGS allows for distinction between neutral and non-neutral markers. By
      screening populations on thousands of single nucleotide polymorphism markers,
      signals of selection can be found for some markers. Variation in these markers
      will give insight into functional rather than neutral genetic variation. Third,
      NGS facilitates the study of gene expression. Conservation genomics will increase
      our insight in how the environment and genes interact to affect phenotype and
      fitness. In addition, the NGS approach opens a way to study processes such as
      inbreeding depression and local adaptation mechanistically. Conservation genetics
      programs are directed to a fundamental understanding of the processes involved in
      conservation genetics and should preferably be started in species for which large
      databases on ecology, demography and genetics are available. Here, we describe
      and illustrate the connection between the application of NGS technologies and the
      research questions in conservation. The perspectives of conservation genomics
      programs are also discussed. 

PMID- 25568038
TI  - A crucial step toward realism: responses to climate change from an evolving
      metacommunity perspective.
AB  - We need to understand joint ecological and evolutionary responses to climate
      change to predict future threats to biological diversity. The 'evolving
      metacommunity' framework emphasizes that interactions between ecological and
      evolutionary mechanisms at both local and regional scales will drive community
      dynamics during climate change. Theory suggests that ecological and evolutionary
      dynamics often interact to produce outcomes different from those predicted based
      on either mechanism alone. We highlight two of these dynamics: (i) species
      interactions prevent adaptation of nonresident species to new niches and (ii)
      resident species adapt to changing climates and thereby prevent colonization by
      nonresident species. The rate of environmental change, level of genetic
      variation, source-sink structure, and dispersal rates mediate between these
      potential outcomes. Future models should evaluate multiple species, species
      interactions other than competition, and multiple traits. Future experiments
      should manipulate factors such as genetic variation and dispersal to determine
      their joint effects on responses to climate change. Currently, we know much more
      about how climates will change across the globe than about how species will
      respond to these changes despite the profound effects these changes will have on
      global biological diversity. Integrating evolving metacommunity perspectives into
      climate change biology should produce more accurate predictions about future
      changes to species distributions and extinction threats. 

PMID- 25568039
TI  - Genotype * genotype interactions between the toxic cyanobacterium Microcystis and
      its grazer, the waterflea Daphnia.
AB  - Toxic algal blooms are an important problem worldwide. The literature on toxic
      cyanobacteria blooms in inland waters reports widely divergent results on whether
      zooplankton can control cyanobacteria blooms or cyanobacteria suppress
      zooplankton by their toxins. Here we test whether this may be due to genotype *
      genotype interactions, in which interactions between the large-bodied and
      efficient grazer Daphnia and the widespread cyanobacterium Microcystis are not
      only dependent on Microcystis strain or Daphnia genotype but are specific to
      genotype * genotype combinations. We show that genotype * genotype interactions
      are important in explaining mortality in short-time exposures of Daphnia to
      Microcystis. These genotype * genotype interactions may result in local
      coadaptation and a geographic mosaic of coevolution. Genotype * genotype
      interactions can explain why the literature on zooplankton-cyanobacteria
      interactions is seemingly inconsistent, and provide hope that zooplankton can
      contribute to the suppression of cyanobacteria blooms in restoration projects. 

PMID- 25568040
TI  - Fates beyond traits: ecological consequences of human-induced trait change.
AB  - Human-induced trait change has been documented in freshwater, marine, and
      terrestrial ecosystems worldwide. These trait changes are driven by phenotypic
      plasticity and contemporary evolution. While efforts to manage human-induced
      trait change are beginning to receive some attention, managing its ecological
      consequences has received virtually none. Recent work suggests that contemporary
      trait change can have important effects on the dynamics of populations,
      communities, and ecosystems. Therefore, trait changes caused by human activity
      may be shaping ecological dynamics on a global scale. We present evidence for
      important ecological effects associated with human-induced trait change in a
      variety of study systems. These effects can occur over large spatial scales and
      impact system-wide processes such as trophic cascades. Importantly, the magnitude
      of these effects can be on par with those of traditional ecological drivers such
      as species presence. However, phenotypic change is not always an agent of
      ecological change; it can also buffer ecosystems against change. Determining the
      conditions under which phenotypic change may promote vs prevent ecological change
      should be a top research priority. 

PMID- 25568041
TI  - The implications of nongenetic inheritance for evolution in changing
      environments.
AB  - Nongenetic inheritance is a potentially important but poorly understood factor in
      population responses to rapid environmental change. Accumulating evidence
      indicates that nongenetic inheritance influences a diverse array of traits in all
      organisms and can allow for the transmission of environmentally induced
      phenotypic changes ('acquired traits'), as well as spontaneously arising and
      highly mutable variants. We review models of adaptation to changing environments
      under the assumption of a broadened model of inheritance that incorporates
      nongenetic mechanisms of transmission, and survey relevant empirical examples.
      Theory suggests that nongenetic inheritance can increase the rate of both
      phenotypic and genetic change and, in some cases, alter the direction of change.
      Empirical evidence shows that a diversity of phenotypes - spanning a continuum
      from adaptive to pathological - can be transmitted nongenetically. The presence
      of nongenetic inheritance therefore complicates our understanding of evolutionary
      responses to environmental change. We outline a research program encompassing
      experimental studies that test for transgenerational effects of a range of
      environmental factors, followed by theoretical and empirical studies on the
      population-level consequences of such effects. 

PMID- 25568042
TI  - Evolution in biodiversity policy - current gaps and future needs.
AB  - The intensity and speed of human alterations to the planet's ecosystems are
      yielding our static, ahistorical view of biodiversity obsolete. Human actions
      frequently trigger fast evolutionary responses, affect extant genetic variation
      and result in the establishment of new communities and co-evolutionary networks
      for which we lack past analogues. Contemporary evolution interplays with
      ecological changes to determine the response of organisms and ecosystems to
      anthropogenic pressures. Examples on wild species include responses to harvest
      (e.g. fisheries, hunting, angling), habitat loss and fragmentation (e.g. genetic
      effects of isolation), biotic exchange (e.g. evolutionary responses to control
      measures), climate change (e.g. local adaptation and its interplay with dispersal
      processes) and the responses of endangered species to conservation measures. A
      review of international and EU biodiversity policies showed numerous
      opportunities for the integration of evolutionary knowledge, with the realistic
      prospect of improving their efficacy. Such opportunities should be extended to
      other sectoral policies of direct relevance for biodiversity - notably nature
      conservation, fisheries, agriculture, water resources, spatial planning and
      climate change. These avenues for improvement are, however, challenged by the low
      level of enforcement of biodiversity policies, linked to the nonbinding nature of
      most biodiversity-policy documents, and the decreasing representation of
      biodiversity in EU's research policy. 

PMID- 25568043
TI  - Adaptive potential of ash (Fraxinus excelsior) populations against the novel
      emerging pathogen Hymenoscyphus pseudoalbidus.
AB  - An emerging infectious pathogen Hymenoscyphus pseudoalbidus has spread across
      much of Europe within recent years causing devastating damage on European common
      ash trees (Fraxinus excelsior) and associated plant communities. The present
      study demonstrates the presence of additive genetic variation in susceptibility
      of natural F. excelsior populations to the new invasive disease. We observe high
      levels of additive variation in the degree of susceptibility with relatively low
      influence of environmental factors (narrow-sense heritability = 0.37-0.52). Most
      native trees are found to be highly susceptible, and we estimate that only around
      1% has the potential of producing offspring with expected crown damage of <10%
      under the present disease pressure. The results suggest that the presence of
      additive genetic diversity in natural F. excelsior populations can confer the
      species with important ability to recover, but that low resistance within natural
      European populations is to be expected because of a low frequency of the hypo
      sensitive trees. Large effective population sizes will be required to avoid
      genetic bottlenecks. The role of artificial selection and breeding for protection
      of the species is discussed based on the findings. 

PMID- 25568044
TI  - Modeling intraspecific adaptation of Abies sachalinensis to local altitude and
      responses to global warming, based on a 36-year reciprocal transplant experiment.
AB  - Intraspecific adaptation in Abies sachalinensis was examined using models based
      on long-term monitoring data gathered during a reciprocal transplant experiment
      with eight seed source populations and six transplantation sites along an
      altitudinal gradient. The consequence of local adaptation was evaluated by
      testing the home-site advantage for upslope and downslope transplants at five
      ages. The populations' fitness-linked trait was set as their productivity (tree
      height * survival rate) at each age. The effects of global warming were evaluated
      on the basis of the 36-year performance of downslope transplants. Evidence was
      found for adaptive genetic variation affecting both height and survival from an
      early age. Increasing the distance between seed source and planting site
      significantly reduced productivity for both upslope and downslope
      transplantation, demonstrating the existence of a significant home-site
      advantage. The decrease in productivity was most distinct for upslope
      transplantations, indicating strong local adaptation to high altitudes. Global
      warming is predicted to increase the productivity of high-altitude populations.
      However, owing to their existing local adaptation, all tested populations
      exhibited lower productivity under warming than demes that were optimal for the
      new climate. These negative predictions should be considered when planning the
      management of locally adapted plant species such as A. sachalinensis. 

PMID- 25568045
TI  - Evolutionary and ecological feedbacks of the survival cost of reproduction.
AB  - Arguably the most fundamental of trade-offs in life-history evolution is the
      increase in natural mortality resulting from sexual maturity and reproduction.
      Despite its central importance, this increase in mortality, a survival cost,
      garners surprisingly little attention in fish and fisheries modeling studies. We
      undertook an exploratory analysis to evaluate the consequences of this omission
      for life-history projections. To this end, we developed a simulation approach
      that integrates quantitative genetics into the ecological dynamics of a fish
      population and parameterized the model for Atlantic cod (Gadus morhua, L.). When
      compared to simulations in which the mortality of immature and mature individuals
      is equal, the inclusion of a survival cost results in larger asymptotic body
      size, older age at maturity, and larger size at maturity. We also find that
      measures of population productivity (spawning stock biomass, recruits-per
      spawner) are overestimated if the survival cost is excluded. This sensitivity of
      key metrics of population growth rate and reproductive capacity to the magnitude
      of the survival cost of reproduction underscores the need to explicitly account
      for this trade-off in projections of fish population responses to natural and
      anthropogenic environmental change, including fisheries. 

PMID- 25568047
TI  - Interpopulation variation in allelopathic traits informs restoration of invaded
      landscapes.
AB  - Invasive species can show substantial genetic variation in ecologically important
      traits, across ranges as well within the introduced range. If these traits affect
      competition with native species, then management may benefit from considering the
      genetic landscape of the invader. Across their introduced range, Alliaria
      petiolata populations vary in their investment in allelopathic traits according
      to invasion history, which could lead to gradients of impact on native species.
      Red oak (Quercus rubra) seedlings were transplanted into eight A. petiolata
      invaded sites that varied in their invasion history and allelochemical
      concentrations. At each site, an invader removal treatment was crossed with
      experimental inoculations of native soil biota, to test whether the benefits of
      these restoration actions differed across invader populations. Q. rubra seedlings
      grew faster in invader populations with a longer invasion history and lower
      allelochemical concentrations. Invader removal and soil inoculation interacted to
      determine seedling growth, with the benefits of soil inoculation increasing in
      younger and more highly allelopathic invader populations. A greenhouse experiment
      using soils collected from experimentally inoculated field plots found similar
      patterns. These results suggest that the impact of this invader varies across
      landscapes and that knowledge of this variation could improve the efficacy and
      efficiency of restoration activities. 

PMID- 25568046
TI  - Host tracking or cryptic adaptation? Phylogeography of Pediobius saulius
      (Hymenoptera, Eulophidae), a parasitoid of the highly invasive horse-chestnut
      leafminer.
AB  - Classical biological control is often advocated as a tool for managing invasive
      species. However, accurate evaluations of parasitoid species complexes and
      assessment of host specificity are impeded by the lack of morphological
      variation. Here, we study the possibility of host races/species within the
      eulophid wasp Pediobius saulius, a pupal generalist parasitoid that parasitize
      the highly invasive horse-chestnut leaf-mining moth Cameraria ohridella. We
      analysed the population genetic structure, host associations and phylogeographic
      patterns of P. saulius in Europe using the COI mitochondrial gene. This marker
      strongly supports a division into at least five highly differentiated parasitoid
      complexes, within two of which clades with differing degrees of host
      specialization were found: a Balkan clade that mainly (but not only) attacks C.
      ohridella and a more generalist European group that attacks many hosts, including
      C. ohridella. The divergence in COI (up to 7.6%) suggests the existence of
      cryptic species, although this is neither confirmed by nuclear divergence nor
      morphology. We do not find evidence of host tracking. The higher parasitism rates
      observed in the Balkans and the scarcity of the Balkan-Cameraria haplotypes out
      of the Balkans open the possibility of using these Balkan haplotypes as
      biological control agents of C. ohridella elsewhere in Europe. 

PMID- 25568048
TI  - Blocking the evolution of insecticide-resistant malaria vectors with a
      microsporidian.
AB  - Finding a way to block the evolution insecticide resistance would be a major
      breakthrough for the control of malaria. We suggest that this may be possible by
      introducing a stress into mosquito populations that restores the sensitivity of
      genetically resistant mosquitoes and that decreases their longevity when they are
      not exposed to insecticide. We use a mathematical model to show that, despite the
      intense selection pressure imposed by insecticides, moderate levels of stress
      might tip the evolutionary balance between costs and benefits of resistance
      toward maintaining sensitivity. Our experimental work with the microsporidian
      parasite Vavraia culicis infecting two lines of resistant mosquitoes and a
      sensitive line suggests that it may indeed be possible to stress the mosquitoes
      in the required way. The mortality of resistant mosquitoes 24 h after exposure to
      the insecticide was up to 8.8 times higher in infected than in uninfected ones;
      if mosquitoes were not exposed to the insecticide, resistant mosquitoes infected
      by the microsporidian lived about half as long as uninfected ones and insecticide
      sensitive mosquitoes (with or without the parasite). Our results suggest that
      biopesticides or other insecticides that interfere with the expression of
      resistance may help to manage insecticide resistance in programs of malaria
      control. 

PMID- 25568049
TI  - No recent adaptive selection on the apyrase of Mediterranean Phlebotomus:
      implications for using salivary peptides to vaccinate against canine
      leishmaniasis.
AB  - Vaccine development is informed by a knowledge of genetic variation among antigen
      alleles, especially the distribution of positive and balancing selection in
      populations and species. A combined approach using population genetic and
      phylogenetic methods to detect selective signatures can therefore be informative
      for identifying vaccine candidates. Parasitic Leishmania species cause the
      disease leishmaniasis in humans and mammalian reservoir hosts after inoculation
      by female phlebotomine sandflies. Like other arthropod vectors of disease agents,
      sandflies use salivary peptides to counteract host haemostatic and
      immunomodulatory responses during bloodfeeding, and these peptides are vaccine
      candidates because they can protect against Leishmania infection. We detected no
      contemporary adaptive selection on one salivary peptide, apyrase, in 20
      populations of Phlebotomus ariasi, a European vector of Leishmania infantum.
      Maximum likelihood branch models on a gene phylogeny showed apyrase to be a
      single copy in P. ariasi but an ancient duplication event associated with
      temporary positive selection was observed in its sister group, which contains
      most Mediterranean vectors of L. infantum. The absence of contemporary adaptive
      selection on the apyrase of P. ariasi may result from this sandfly's
      opportunistic feeding behaviour. Our study illustrates how the molecular
      population genetics of arthropods can help investigate the potential of salivary
      peptides for disease control and for understanding geographical variation in
      vector competence. 

PMID- 25568050
TI  - Genetic and maternal effects on tail spine and body length in the invasive spiny
      water flea (Bythotrephes longimanus).
AB  - Interest in the evolution of invasive species has grown in recent years, yet few
      studies have investigated sources of variation in invasive species traits
      experiencing natural selection. The spiny water flea, Bythotrephes longimanus, is
      an invasive zooplankton in the Great Lakes that exhibits seasonal changes in tail
      spine and body length consistent with natural selection. Evolution of
      Bythotrephes traits, however, depends on the presence and magnitude of
      quantitative genetic variation, which could change within or across years. Clonal
      analysis of wild-captured Bythotrephes indicated that variance components for
      distal spine length were variable among but not within years. Spine length was
      always heritable but was not always influenced by maternal effects. In contrast,
      variance components for body length varied both within and among years, but
      likewise body length was always heritable and not always influenced by maternal
      effects. Results indicate that important Bythotrephes traits have heritable
      variation comparable to native species and other invasive species that would
      enable an evolutionary response to natural selection. This evolutionary capacity
      could contribute to the widespread success and dramatic effects of Bythotrephes
      invasion in systems with diverse biotic and abiotic conditions. 

PMID- 25568051
TI  - The Role of Acoustic Radiation Force Impulse Elastography in the Differentiation
      of Infectious and Neoplastic Liver Lesions.
AB  - We aimed to evaluate the effectiveness of acoustic radiation force impulse (ARFI)
      elastography in differentiating between hepatic lesions. The prospective study
      included 117 patients with liver masses. Shear wave velocity (SWV) values for
      lesions were determined by ARFI imaging and compared statistically. The
      difference between SWV values for benign and malignant hepatic masses was
      significant (p < 0.01). The threshold SWV value for malignant hepatic lesions was
      established at 2.52 m/s, and the sensitivity and specificity of this cut-off
      value were 97% and 66%, respectively. We concluded that ARFI elastography
      provides supplementary data that aid in the differential diagnosis of liver
      masses. 

PMID- 25568053
TI  - Gene flow among wild and domesticated almond species: insights from chloroplast
      and nuclear markers.
AB  - Hybridization has played a central role in the evolutionary history of
      domesticated plants. Notably, several breeding programs relying on gene
      introgression from the wild compartment have been performed in fruit tree species
      within the genus Prunus but few studies investigated spontaneous gene flow among
      wild and domesticated Prunus species. Consequently, a comprehensive understanding
      of genetic relationships and levels of gene flow between domesticated and wild
      Prunus species is needed. Combining nuclear and chloroplastic microsatellites, we
      investigated the gene flow and hybridization among two key almond tree species,
      the cultivated Prunus dulcis and one of the most widespread wild relative Prunus
      orientalis in the Fertile Crescent. We detected high genetic diversity levels in
      both species along with substantial and symmetric gene flow between the
      domesticated P. dulcis and the wild P. orientalis. These results were discussed
      in light of the cultivated species diversity, by outlining the frequent
      spontaneous genetic contributions of wild species to the domesticated
      compartment. In addition, crop-to-wild gene flow suggests that ad hoc transgene
      containment strategies would be required if genetically modified cultivars were
      introduced in the northwestern Mediterranean. 

PMID- 25568052
TI  - A large-scale, in vivo transcription factor screen defines bivalent chromatin as
      a key property of regulatory factors mediating Drosophila wing development.
AB  - Transcription factors (TFs) are key regulators of cell fate. The estimated 755
      genes that encode DNA binding domain-containing proteins comprise ~ 5% of all
      Drosophila genes. However, the majority has remained uncharacterized so far due
      to the lack of proper genetic tools. We generated 594 site-directed transgenic
      Drosophila lines that contain integrations of individual UAS-TF constructs to
      facilitate spatiotemporally controlled misexpression in vivo. All transgenes were
      expressed in the developing wing, and two-thirds induced specific phenotypic
      defects. In vivo knockdown of the same genes yielded a phenotype for 50%, with
      both methods indicating a great potential for misexpression to characterize novel
      functions in wing growth, patterning, and development. Thus, our UAS-TF library
      provides an important addition to the genetic toolbox of Drosophila research,
      enabling the identification of several novel wing development-related TFs. In
      parallel, we established the chromatin landscape of wing imaginal discs by ChIP
      seq analyses of five chromatin marks and RNA Pol II. Subsequent clustering
      revealed six distinct chromatin states, with two clusters showing enrichment for
      both active and repressive marks. TFs that carry such "bivalent" chromatin are
      highly enriched for causing misexpression phenotypes in the wing, and analysis of
      existing expression data shows that these TFs tend to be differentially expressed
      across the wing disc. Thus, bivalently marked chromatin can be used as a marker
      for spatially regulated TFs that are functionally relevant in a developing
      tissue.

PMID- 25568055
TI  - Genetic structure and local adaptation of European wheat yellow rust populations:
      the role of temperature-specific adaptation.
AB  - Environmental heterogeneity influences coevolution and local adaptation in host
      parasite systems. This also concerns applied issues, because the geographic range
      of parasites may depend on their capacity to adapt to abiotic conditions. We
      studied temperature-specific adaptation in the wheat yellow/stripe rust pathogen,
      Puccinia striiformis f.sp. tritici (PST). Using laboratory experiments, PST
      isolates from northern and southern France were studied for their ability to
      germinate and to infect bread and durum wheat cultivars over a temperature
      gradient. Pathogen origin * temperature interactions for infectivity and
      germination rate suggest local adaptation to high- versus low-temperature regimes
      in south and north. Competition experiments in southern and northern field sites
      showed a general competitive advantage of southern over northern isolates. This
      advantage was particularly pronounced in the southern 'home' site, consistent
      with a model integrating laboratory infectivity and field temperature variation.
      The stable PST population structure in France likely reflects adaptation to
      ecological and genetic factors: persistence of southern PST may be due to
      adaptation to the warmer Mediterranean climate; and persistence of northern PST
      can be explained by adaptation to commonly used cultivars, for which southern
      isolates are lacking the relevant virulence genes. Thus, understanding the role
      of temperature-specific adaptations may help to improve forecast models or
      breeding programmes. 

PMID- 25568054
TI  - Molecular epidemiology of Aleutian disease virus in free-ranging domestic,
      hybrid, and wild mink.
AB  - Aleutian mink disease (AMD) is a prominent infectious disease in mink farms. The
      AMD virus (AMDV) has been well characterized in Europe where American mink
      (Neovison vison) are an introduced species; however, in North America, where
      American mink are native and the disease is thought to have originated, the
      virus' molecular epidemiology is unknown. As such, we characterized viral
      isolates from Ontario free-ranging mink of domestic, hybrid, and wild origin at
      two proteins: NS1, a nonstructural protein, and VP2, a capsid protein. AMDV DNA
      was detected in 25% of free-ranging mink (45 of 183), indicating prevalent active
      infection. Median-joining networks showed that Ontario AMDV isolates formed two
      subgroups in the NS1 region and three in the VP2 region, which were somewhat
      separate from, but closely related to, AMDVs circulating in domestic mink
      worldwide. Molecular analyses showed evidence of AMDV crossing from domestic to
      wild mink. Our results suggest that AMDV isolate grouping is linked to both wild
      endogenous reservoirs and the long-term global trade in domestic mink, and that
      AMD spills back and forth between domestic and wild mink. As such, biosecurity on
      mink farms is warranted to prevent transmission of the disease between mink farms
      and the wild. 

PMID- 25568056
TI  - The Red Queen and the seed bank: pathogen resistance of ex situ and in situ
      conserved barley.
AB  - Plant geneticists have proposed that the dynamic conservation of crop plants in
      farm environments (in situ conservation) is complementary to static conservation
      in seed banks (ex situ conservation) because it may help to ensure adaptation to
      changing conditions. Here, we test whether collections of a traditional variety
      of Moroccan barley (Hordeum vulgare ssp. vulgare) conserved ex situ showed
      differences in qualitative and quantitative resistance to the endemic fungal
      pathogen, Blumeria graminis f.sp. hordei, compared to collections that were
      continuously cultivated in situ. In detached-leaf assays for qualitative
      resistance, there were some significant differences between in situ and ex situ
      conserved collections from the same localities. Some ex situ conserved
      collections showed lower resistance levels, while others showed higher resistance
      levels than their in situ conserved counterparts. In field trials for
      quantitative resistance, similar results were observed, with the highest
      resistance observed in situ. Overall, this study identifies some cases where the
      Red Queen appears to drive the evolution of increased resistance in situ.
      However, in situ conservation does not always result in improved adaptation to
      pathogen virulence, suggesting a more complex evolutionary scenario, consistent
      with several published examples of plant-pathogen co-evolution in wild systems. 

PMID- 25568057
TI  - Can we understand modern humans without considering pathogens?
AB  - Throughout our evolutionary history, humankind has always lived in contact with
      large numbers of pathogens. Some cultural traits, such as sedentarization and
      animal domestication, have considerably increased new parasitic contacts and
      epidemic transitions. Here, we review the various phenotypic traits that have
      been proposed to be affected by the highly parasitic human environment, including
      fertility, birth weight, fluctuating asymmetry, body odours, food recipes, sexual
      behaviour, pregnancy sickness, language, religion and intellectual quotient. We
      also discuss how such knowledge is important to understanding several aspects of
      the current problems faced by humanity in our changing world and to predicting
      the long-term consequences of parasite eradication policies on our health and
      well-being. The study of the evolutionary interactions between humans and
      parasites is a burgeoning and most promising field, as demonstrated by the recent
      increasing popularity of Darwinian medicine. 

PMID- 25568058
TI  - Discordant introgression in a rapidly expanding hybrid swarm.
AB  - The erosion of species boundaries can involve rapid evolutionary change.
      Consequently, many aspects of the process remain poorly understood, including the
      formation, expansion, and evolution of hybrid swarms. Biological invasions
      involving hybridization present exceptional opportunities to study the erosion of
      species boundaries because timelines of interactions and outcomes are frequently
      well known. Here, we examined clinal variation across codominant and maternally
      inherited genetic markers as well as phenotypic traits to characterize the
      expansion and evolution of a hybrid swarm between native Cyprinella venusta and
      invasive Cyprinella lutrensis minnows. Discordant introgression of phenotype,
      microsatellite multilocus genotype, and mtDNA haplotype indicates that the
      observable expansion of the C. venusta * C. lutrensis hybrid swarm is a false
      invasion front. Both parental and hybrid individuals closely resembling C.
      lutrensis are numerically dominant in the expansion wake, indicating that the non
      native parental phenotype may be selectively favored. These findings show that
      cryptic introgression can extend beyond the phenotypic boundaries of hybrid
      swarms and that hybrid swarms likely expand more rapidly than can be documented
      from phenotypic variation alone. Similarly, dominance of a single parental
      phenotype following an introduction event may lead to instances of species
      erosion being mistaken for species displacement without hybridization. 

PMID- 25568059
TI  - Genetic structure and rabies spread potential in raccoons: the role of landscape
      barriers and sex-biased dispersal.
AB  - Identifying natural barriers to movements of hosts associated with infectious
      diseases is essential for developing effective control strategies. Raccoon rabies
      variant (RRV) is a zoonosis of concern for humans because its main vector, the
      raccoon (Procyon lotor), is found near residential areas. In Quebec, Canada, all
      cases of RRV found in raccoons since 2006 were detected on the eastern side of
      the Richelieu River, suggesting that this river acts as a barrier to gene flow
      and thus the potential for RRV to spread. The objectives of this study were to
      characterize the genetic structure of raccoon populations and assess the effect
      of the Richelieu River on the population structure in southern Quebec, Canada. We
      also evaluated whether RRV spread potential differed between sex and at a larger
      spatial scale. Our analyses revealed a weak signal of genetic differentiation
      among individuals located on each side of the Richelieu River. At a larger
      spatial scale, genetic structuring was weak. Our results suggest that rivers
      might not always efficiently restrain raccoon movements and spread of RRV. We
      suggest that the difference in genetic structure found between sexes can be
      partly explained by male movements during the breeding season in winter, when ice
      bridges allow passage over most rivers in Quebec. 

PMID- 25568060
TI  - Toward responsible stock enhancement: broadcast spawning dynamics and adaptive
      genetic management in white seabass aquaculture.
AB  - The evolutionary effects captive-bred individuals that can have on wild
      conspecifics are necessary considerations for stock enhancement programs, but
      breeding protocols are often developed without the knowledge of realized
      reproductive behavior. To help fill that gap, parentage was assigned to offspring
      produced by a freely mating group of 50 white seabass (Atractoscion nobilis), a
      representative broadcast spawning marine finfish cultured for conservation.
      Similar to the well-known and closely related red drum (Sciaenops ocellatus), A.
      nobilis exhibited large variation in reproductive success. More males contributed
      and contributed more equally than females within and among spawns in a mating
      system best described as lottery polygyny. Two females produced 27% of the
      seasonal offspring pool and female breeding effective size averaged 1.85 per
      spawn and 12.38 seasonally, whereas male breeding effective size was higher (6.42
      and 20.87, respectively), with every male contributing 1-7% of offspring.
      Further, females batch spawned every 1-5 weeks, while males displayed continuous
      reproductive readiness. Sex-specific mating strategies resulted in multiple
      successful mate pairings and a breeding effective to census size ratio of >=0.62.
      Understanding a depleted species' mating system allowed management to more
      effectively utilize parental genetic variability for culture, but the fitness
      consequences of long-term stocking can be difficult to address. 

PMID- 25568063
TI  - Examining the link between conception risk and intergroup bias: the importance of
      conceptual coherence.

PMID- 25568061
TI  - Liposcale: a novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR
      spectroscopy.
AB  - Determination of lipoprotein particle size and number using advanced lipoprotein
      tests (ALTs) is of particular importance to improve cardiovascular risk
      prediction. Here we present the Liposcale test, a novel ALT based on 2D diffusion
      ordered (1)H NMR spectroscopy. Our method uses diffusion coefficients to provide
      a direct measure of the mean particle sizes and numbers. Using 177 plasma samples
      from healthy individuals and the concentration of ApoB and ApoA from isolated
      lipoprotein fractions, our test showed a stronger correlation between the NMR
      derived lipoprotein particle numbers and apolipoprotein concentrations than the
      LipoProfile((r)) test commercialized by Liposcience. We also converted LDL
      particle numbers to ApoB equivalents (milligrams per deciliter) and our test
      yielded similar values of LDL-ApoB to the LipoProfile((r)) test (absolute mean
      bias of 8.5 and 7.4 mg/dl, respectively). In addition, our HDL particle number
      values were more concordant with the calibrated values determined recently using
      ion mobility. Finally, principal component analysis distinguished type 2 diabetic
      patients with and without atherogenic dyslipidemia (AD) on a second cohort of 307
      subjects characterized using the Liposcale test (area under the curve = 0.88) and
      showed concordant relationships between variables explaining AD. Altogether, our
      method provides reproducible and reliable characterization of lipoprotein
      particles and it is applicable to pathological states such as AD. 

PMID- 25568064
TI  - More power to the unconscious: conscious, but not unconscious, exogenous
      attention requires location variation.
AB  - Substantial evidence suggests that unconscious processing can be characterized as
      a lesser or weaker version of conscious processing. To test this notion, we
      designed a novel repeated-cuing procedure based on exogenous attention: The
      location of the attentional cue was first fixed across blocks (fixed-cue blocks),
      and then the cue was removed in subsequent blocks (no-cue blocks). The visibility
      of the cue was also manipulated. We found that when the cue was invisible, the
      response to a prespecified stimulus in the fixed-cue blocks was faster if the
      stimulus was at the cued location than if it was at the uncued location. But when
      the cue was visible, this cuing effect was abolished, potentially because of an
      awareness-dependent, location-based inhibition mechanism, as revealed by an
      attentional bias against the previously cued location in the no-cue blocks. We
      call this bias negative attentional aftereffect. These results provide novel
      evidence against the weaker-version characterization of unconscious effects,
      highlighting dissociable components of orienting and inhibition in exogenous
      cuing through awareness and temporal dynamics.

PMID- 25568062
TI  - Ext1 heterozygosity causes a modest effect on postprandial lipid clearance in
      humans.
AB  - Elevated nonfasting TG-rich lipoprotein levels are a risk factor for CVD. To
      further evaluate the relevance of LDL-receptor (LDLr) pathway and heparan sulfate
      proteoglycans (HSPGs) in TG homeostasis, we analyzed fasting and postprandial TG
      levels in mice bearing combined heterozygous mutations in both Exostosin (Ext) 1
      and Ldlr, in subjects with hereditary multiple exostosis (HME) due to a
      heterozygous loss-of-function mutation in EXT1 or EXT2 (N = 13), and in patients
      with heterozygous mutations in LDLR [familial hypercholesterolemia (FH)] and SNPs
      in major HSPG-related genes (n = 22). Mice bearing a homozygous mutation in
      hepatic Ext1 exhibited elevated plasma TGs similar to mice lacking other key
      enzymes involved in HSPG assembly. Compound heterozygous mice lacking Ldlr and
      Ext1 showed synergy on plasma TG accumulation and postprandial clearance. In
      human subjects, a trend was observed in HME patients toward reduced postprandial
      TG clearance with a concomitant reduction in chylomicron clearance [area under
      the curve (AUC)-retinyl ester (RE) HME, 844 +/- 127 vs. controls, 646 +/- 119
      nM/h, P = 0.09]. Moreover, in FH subjects with a high HSPG gene score, retinyl
      palmitate excursions were higher (AUC-RE, 2,377 +/- 293 vs. 1,565 +/- 181 nM/h, P
      < 0.05). Incremental AUC-apoB48 was similar between the groups. In conclusion,
      the data are supportive for a minor yet additive role of HSPG in human
      postprandial TG clearance, and further studies are warranted. 

PMID- 25568068
TI  - Immunity in head and neck cancer.
AB  - Head and neck cancers are a diverse group of malignancies that includes an
      increasing number of virally mediated cancers in addition to tumors caused by
      tobacco and alcohol use. In both cases, tumor development is intimately related
      to the host immune system, and the status of an endogenous antitumor response is
      likely prognostic. Virally mediated cancers provide unique targets for preventive
      vaccines that generate immune responses directed against virus-associated
      antigens. Once head and neck tumors develop, they are commonly treated with
      surgery, radiotherapy, and/or chemotherapy. These treatments are associated with
      significant toxicities, and despite this, subgroups of patients respond poorly
      and are likely to relapse and die of their disease. Tumor immunotherapy may allow
      for improvements in both treatment-associated toxicity and outcome. In addition
      to providing specific targets for therapeutic vaccines and adoptive therapy,
      virally associated cancers may also be particularly dependent on immune
      checkpoints; therefore, immune checkpoint inhibitors are being actively tested
      for these diseases. Cancers that are not virally mediated may also respond to
      immunotherapies, and biomarkers that could predict response to immunotherapy
      irrespective of viral status are being evaluated. Multiple ongoing studies are
      testing benefits of immunotherapy in the management of metastatic squamous cell
      carcinoma of the head and neck. Early promising results pave the way for future
      studies that will expand testing to nonmetastatic diseases and other types of
      head and neck cancers. Prospects of combining various immunotherapies and more
      established treatments such as chemotherapy and radiotherapy are very intriguing
      and may provide synergistic benefits.

PMID- 25568067
TI  - Tumors: wounds that do not heal-redux.
AB  - Similarities between tumors and the inflammatory response associated with wound
      healing have been recognized for more than 150 years and continue to intrigue.
      Some years ago, based on our then recent discovery of vascular permeability
      factor (VPF)/VEGF, I suggested that tumors behaved as wounds that do not heal.
      More particularly, I proposed that tumors co-opted the wound-healing response to
      induce the stroma they required for maintenance and growth. Work over the past
      few decades has supported this hypothesis and has put it on a firmer molecular
      basis. In outline, VPF/VEGF initiates a sequence of events in both tumors and
      wounds that includes the following: increased vascular permeability;
      extravasation of plasma, fibrinogen and other plasma proteins; activation of the
      clotting system outside the vascular system; deposition of an extravascular
      fibrin gel that serves as a provisional stroma and a favorable matrix for cell
      migration; induction of angiogenesis and arterio-venogenesis; subsequent
      degradation of fibrin and its replacement by "granulation tissue" (highly
      vascular connective tissue); and, finally, vascular resorption and collagen
      synthesis, resulting in the formation of dense fibrous connective tissue (called
      "scar tissue" in wounds and "desmoplasia" in cancer). A similar sequence of
      events also takes place in a variety of important inflammatory diseases that
      involve cellular immunity.

PMID- 25568069
TI  - The human IgG anti-carbohydrate repertoire exhibits a universal architecture and
      contains specificity for microbial attachment sites.
AB  - Despite the paradigm that carbohydrates are T cell-independent antigens, isotype
      switched glycan-specific immunoglobulin G (IgG) antibodies and polysaccharide
      specific T cells are found in humans. We used a systems-level approach combined
      with glycan array technology to decipher the repertoire of carbohydrate-specific
      IgG antibodies in intravenous and subcutaneous immunoglobulin preparations. A
      strikingly universal architecture of this repertoire with modular organization
      among different donor populations revealed an association between immunogenicity
      or tolerance and particular structural features of glycans. Antibodies were
      identified with specificity not only for microbial antigens but also for a broad
      spectrum of host glycans that serve as attachment sites for viral and bacterial
      pathogens and/or exotoxins. Tumor-associated carbohydrate antigens were
      differentially detected by IgG antibodies, whereas non-IgG2 reactivity was
      predominantly absent. Our study highlights the power of systems biology
      approaches to analyze immune responses and reveals potential glycan antigen
      determinants that are relevant to vaccine design, diagnostic assays, and antibody
      based therapies. 

PMID- 25568070
TI  - Effect of bipolar androgen therapy for asymptomatic men with castration-resistant
      prostate cancer: results from a pilot clinical study.
AB  - Targeting androgen receptor (AR) axis signaling by disrupting androgen-AR
      interactions remains the primary treatment for metastatic prostate cancer.
      Unfortunately, all men develop resistance to primary castrating therapy and
      secondary androgen deprivation therapies (ADTs). Resistance develops in part
      because castration-resistant prostate cancer (CRPC) cells adaptively up-regulate
      AR levels through overexpression, amplification, and expression of ligand
      independent variants in response to chronic exposure to a low-testosterone
      environment. However, preclinical models suggest that AR overexpression
      represents a therapeutic liability that can be exploited via exposure to
      supraphysiologic testosterone to promote CRPC cell death. Preclinical data
      supported a pilot study in which 16 asymptomatic CRPC patients with low to
      moderate metastatic burden were treated with testosterone cypionate (400 mg
      intramuscular; day 1 of 28) and etoposide (100 mg oral daily; days 1 to 14 of
      28). After three cycles, those with a declining prostate-specific antigen (PSA)
      continued on intermittent testosterone therapy monotherapy. Castrating therapy
      was continued to suppress endogenous testosterone production, allowing for rapid
      cycling from supraphysiologic to near-castrate serum testosterone levels, a
      strategy termed bipolar androgen therapy (BAT). BAT was well tolerated and
      resulted in high rates of PSA (7 of 14 evaluable patients) and radiographic
      responses (5 of 10 evaluable patients). Although all men showed eventual PSA
      progression, four men remained on BAT for >=1 year. All patients (10 of 10)
      demonstrated PSA reductions upon receiving androgen-ablative therapies after BAT,
      suggesting that BAT may also restore sensitivity to ADTs. BAT shows promise as
      treatment for CRPC and should be further evaluated in larger trials. 

PMID- 25568072
TI  - Resident memory T cells in human health and disease.
AB  - Resident memory T cells are non-recirculating memory T cells that persist long
      term in epithelial barrier tissues, including the gastrointestinal tract, lung,
      skin, and reproductive tract. Resident memory T cells persist in the absence of
      antigens, have impressive effector functions, and provide rapid on-site immune
      protection against known pathogens in peripheral tissues. A fundamentally
      distinct gene expression program differentiates resident memory T cells from
      circulating T cells. Although these cells likely evolved to provide rapid immune
      protection against pathogens, autoreactive, aberrantly activated, and malignant
      resident memory cells contribute to numerous human inflammatory diseases
      including mycosis fungoides and psoriasis. This review will discuss both the
      science and medicine of resident memory T cells, exploring how these cells
      contribute to healthy immune function and discussing what is known about how
      these cells contribute to human inflammatory and autoimmune diseases. 

PMID- 25568071
TI  - Direct inhibitors of InhA are active against Mycobacterium tuberculosis.
AB  - New chemotherapeutic agents are urgently required to combat the global spread of
      multidrug-resistant tuberculosis (MDR-TB). The mycobacterial enoyl reductase InhA
      is one of the few clinically validated targets in tuberculosis drug discovery. We
      report the identification of a new class of direct InhA inhibitors, the 4-hydroxy
      2-pyridones, using phenotypic high-throughput whole-cell screening. This class of
      orally active compounds showed potent bactericidal activity against common
      isoniazid-resistant TB clinical isolates. Biophysical studies revealed that 4
      hydroxy-2-pyridones bound specifically to InhA in an NADH (reduced form of
      nicotinamide adenine dinucleotide)-dependent manner and blocked the enoyl
      substrate-binding pocket. The lead compound NITD-916 directly blocked InhA in a
      dose-dependent manner and showed in vivo efficacy in acute and established mouse
      models of Mycobacterium tuberculosis infection. Collectively, our structural and
      biochemical data open up new avenues for rational structure-guided optimization
      of the 4-hydroxy-2-pyridone class of compounds for the treatment of MDR-TB. 

PMID- 25568073
TI  - Dose of arm activity training during acute and subacute rehabilitation post
      stroke: a systematic review of the literature.
AB  - AIM: To determine the dose of activity-related arm training undertaken by stroke
      survivors during acute and subacute rehabilitation. METHODS: A systematic review
      of PubMed, CINAHL and EMBASE up to December 2014 was completed. Studies were
      eligible if they defined the dose (time or repetitions) of activity-related arm
      training using observational methods for a cohort of adult stroke survivors
      receiving acute or subacute rehabilitation. All studies were quality appraised
      using an evidence-based learning critical appraisal checklist. Data was analysed
      by method of documented dose per session (minutes, repetitions), environment
      (acute or subacute rehabilitation) and therapy discipline (physiotherapy,
      occupational therapy). RESULTS: Ten studies were included: two observed stroke
      survivors during acute rehabilitation and eight during subacute rehabilitation.
      During acute rehabilitation, one study reported 4.1 minutes per session during
      physiotherapy and 11.2 minutes during occupational therapy, while another study
      reported 5.7 minutes per session during physiotherapy only. During inpatient
      rehabilitation, activity-related arm training was on average undertaken for 4
      minutes per session (range 0.9 to 7.9, n = 4 studies) during physiotherapy and 17
      minutes per session (range 9.3 to 28.9, n = 3 studies) during occupational
      therapy. Repetitions per session were reported by two studies only during
      subacute rehabilitation. One study reported 23 repetitions per session during
      physiotherapy and occupational therapy, while another reported 32 repetitions per
      session across both disciplines. CONCLUSION: The dose of activity-related arm
      training during acute and subacute rehabilitation after stroke is limited.

PMID- 25568074
TI  - Properties of single FDB fibers following a collagenase digestion for studying
      contractility, fatigue, and pCa-sarcomere shortening relationship.
AB  - The objective of this study was to optimize the approach to obtain viable single
      flexor digitorum brevis (FDB) fibers following a collagenase digestion. A first
      aim was to determine the culture medium conditions for the collagenase digestion.
      The MEM yielded better fibers in terms of morphology and contractility than the
      DMEM. The addition of FBS to culture media was crucial to prevent fiber
      supercontraction. The addition of FBS to the physiological solution used during
      an experiment was also beneficial, especially during fatigue. Optimum FBS
      concentration in MEM was 10% (vol/vol), and for the physiological solution, it
      ranged between 0.2 and 1.0%. A second aim was to document the stability of single
      FDB fibers. If tested the day of the preparation, most fibers (~80%) had stable
      contractions for up to 3 h, normal stimulus duration strength to elicit
      contractions, and normal and stable resting membrane potential during prolonged
      microelectrode penetration. A third aim was to document their fatigue kinetics.
      Major differences in fatigue resistance were observed between fibers as expected
      from the FDB fiber-type composition. All sarcoplasmic [Ca(2+)] and sarcomere
      length parameters returned to their prefatigue levels after a short recovery. The
      pCa-sarcomere shortening relationship of unfatigued fibers is very similar to the
      pCa-force curve reported in other studies. The pCa-sarcomere shortening from
      fatigue data is complicated by large decreases in sarcomere length between
      contractions. It is concluded that isolation of single fibers by a collagenase
      digestion is a viable preparation to study contractility and fatigue kinetics.

PMID- 25568075
TI  - In vivo and in vitro evidence that chronic activation of the hexosamine
      biosynthetic pathway interferes with leptin-dependent STAT3 phosphorylation.
AB  - We previously reported that a 2-day peripheral infusion of glucosamine caused
      leptin resistance in rats, suggesting a role for the hexosamine biosynthetic
      pathway (HBP) in the development of leptin resistance. Here we tested leptin
      responsiveness in mice in which HBP activity was stimulated by offering 30%
      sucrose solution in addition to chow and water or by infusing glucosamine. Mice
      were leptin resistant after 33 days of access to sucrose. Resistance was
      associated with increased activity of the HBP and with phosphorylation of
      transcription factor signal transducer and activator of transcription-3 Tyr705
      [pSTAT3(Y705)] but inhibition of suppressor of cytokine signaling 3 in the liver
      and hypothalamus. Intravenous infusion of glucosamine for 3 h stimulated
      pSTAT3(Y705) but prevented leptin-induced phosphorylation of STAT3(S727). In an
      in vitro system, glucose, glucosamine, and leptin each dose dependently increased
      O-linked beta-N-acetylglucosamine (O-GlcNAc) protein and pSTAT3(Y705) in HepG2
      cells. To test the effect of glucose on leptin responsiveness cells were
      incubated in 5.5 mM (LG) or 20 mM (HG) glucose for 18 h and were treated with 0
      or 50 ng/ml leptin for 15 min. HG alone and LG + leptin produced similar
      increases in O-GlcNAc protein, glutamine fructose-6-phosphate amidotransferase
      (GFAT), and pSTAT3(Y705) compared with LG media. Leptin did not stimulate these
      proteins in HG cells, suggesting leptin resistance. Leptin-induced pSTAT3(S727)
      was prevented by HG media. Inhibition of GFAT with azaserine prevented LG +
      leptin and HG stimulation of pSTAT3. These data demonstrate development of leptin
      resistance in sucrose-drinking mice and provide new evidence of leptin-induced
      stimulation of the HBP.

PMID- 25568076
TI  - Early-life physical activity reverses metabolic and Foxo1 epigenetic
      misregulation induced by gestational sleep disturbance.
AB  - Sleep disorders are highly prevalent during late pregnancy and can impose adverse
      effects, such as preeclampsia and diabetes. However, the consequences of sleep
      fragmentation (SF) on offspring metabolism and epigenomic signatures are unclear.
      We report that physical activity during early life, but not later, reversed the
      increased body weight, altered glucose and lipid homeostasis, and increased
      visceral adipose tissue in offspring of mice subjected to gestational SF (SFo).
      The reversibility of this phenotype may reflect epigenetic mechanisms induced by
      SF during gestation. Accordingly, we found that the metabolic master switch Foxo1
      was epigenetically misregulated in SFo livers in a temporally regulated fashion.
      Temporal Foxo1 analysis and its gluconeogenetic targets revealed that the
      epigenetic abnormalities of Foxo1 precede the metabolic syndrome phenotype.
      Importantly, regular physical activity early, but not later in life, reversed
      Foxo1 epigenetic misregulation and altered the metabolic phenotype in
      gestationally SF-exposed offspring. Thus, we have identified a restricted
      postnatal period during which lifestyle interventions may reverse the Foxo1
      epigenetically mediated risk for metabolic dysfunction later in the life, as
      induced by gestational sleep disorders.

PMID- 25568078
TI  - Acute exercise increases insulin sensitivity in adult sheep: a new preclinical
      model.
AB  - In healthy humans and rodents, chronic and acute exercise improves subsequent
      insulin sensitivity of skeletal muscle. A large animal species with similar
      metabolic responses to exercise would permit longitudinal studies, including
      repeated biopsies of muscle and other tissues not possible in rodents, and enable
      study of interactions with insulin-resistant physiological states not feasible in
      humans. Therefore, we examined whether acute exercise increases insulin
      sensitivity in adult sheep. Insulin sensitivity was measured by hyperinsulinemic
      euglycemic clamp (HEC) in mature female sheep (n = 7). Sheep were familiarized to
      treadmill walking and then performed an acute exercise bout (30 min, 8% slope, up
      to 4.4 km/h). A second HEC was conducted ~18 h after the acute exercise. Musculus
      semimembranosus biopsies were obtained before and after each HEC. Glucose
      infusion rate during the HEC increased 40% (P = 0.003) and insulin sensitivity
      (glucose infusion rate/plasma insulin concentration) increased 32% (P = 0.028)
      after acute exercise. Activation of proximal insulin signaling in skeletal muscle
      after the HEC, measured as Ser(473) phosphorylation of Akt, increased
      approximately five-fold in response to insulin (P < 0.001) and was unaltered by
      acute exercise performed 18 h earlier. PGC1alpha and GLUT4 protein, glycogen
      content and citrate synthase activity in skeletal muscle did not change in
      response to insulin or exercise. In conclusion, improved insulin sensitivity and
      unchanged proximal insulin signaling on the day after acute exercise in sheep are
      consistent with responses in humans and rodents, suggesting that the sheep is an
      appropriate large-animal model in which to study responses to exercise.

PMID- 25568077
TI  - Spaceflight and simulated microgravity cause a significant reduction of key gene
      expression in early T-cell activation.
AB  - Healthy immune function depends on precise regulation of lymphocyte activation.
      During the National Aeronautics and Space Administration (NASA) Apollo and
      Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity
      under microgravity (MUg) conditions. Scientists on the ground use two models of
      simulated MUg (sMUg): 1) the rotating wall vessel (RWV) and 2) the random
      positioning machine (RPM), to study the effects of altered gravity on cell
      function before advancing research to the true MUg when spaceflight opportunities
      become available on the International Space Station (ISS). The objective of this
      study is to compare the effects of true MUg and sMUg on the expression of key
      early T-cell activation genes in mouse splenocytes from spaceflight and ground
      animals. For the first time, we compared all three conditions of microgravity
      spaceflight, RPM, and RWV during immune gene activation of Il2, Il2ralpha,
      Ifngamma, and Tagap; moreover, we confirm two new early T-cell activation genes,
      Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative
      real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene
      expression in activated ground samples with suppression of mouse immune function
      in spaceflight, RPM, and RWV samples. These findings indicate that sMUg models
      provide an excellent test bed for scientists to develop baseline studies and
      augment true MUg in spaceflight experiments. Ultimately, sMUg and spaceflight
      studies in lymphocytes may provide insight into novel regulatory pathways,
      benefiting both future astronauts and those here on earth suffering from immune
      disorders.

PMID- 25568080
TI  - Quantitative evaluation of annular bright-field phase images in STEM.
AB  - A phase reconstruction method based on multiple scanning transmission electron
      microscope (STEM) images was evaluated quantitatively using image simulations.
      The simulation results indicated that the phase shift caused by a single atom was
      proportional to the 0.6th power of the atomic number Z. For a thin SrTiO3 [001]
      crystal, the reconstructed phase at each atomic column increased according to the
      specimen thickness. The STEM phase images can quantify the oxygen vacancy
      concentration if the thickness is less than several nanometers.

PMID- 25568079
TI  - Comparative effects of intraduodenal protein and lipid on ghrelin, peptide YY,
      and leptin release in healthy men.
AB  - Intraduodenal infusion of lipid or protein potently reduces subsequent energy
      intake. There is evidence that the underlying mechanisms differ significantly
      between the two nutrients. While intraduodenal lipid stimulates glucagon-like
      peptide-1 and CCK much more than protein, the release of insulin and glucagon is
      substantially greater in response to protein. Ghrelin and PYY are both involved
      in short-term regulation, while leptin is a long-term regulator, of energy
      balance; the acute effects of nutrients on leptin release are unclear. We
      investigated the comparative effects of intraduodenal lipid and protein on plasma
      ghrelin, PYY, and leptin concentrations. Thirteen lean, young men received 90-min
      intraduodenal infusions of protein (whey hydrolysate) or lipid (long-chain
      triglyceride emulsion) at a rate of 3 kcal/min, or saline control, on three
      separate days. Blood samples were collected at baseline and regularly during
      infusions. Both lipid and protein potently suppressed plasma ghrelin compared
      with control (both P < 0.001), with no difference between them. While both lipid
      and protein stimulated plasma PYY (P < 0.001), the effect of lipid was
      substantially greater than that of protein (P < 0.001). Neither intraduodenal
      lipid nor protein affected plasma leptin. In conclusion, intraduodenal lipid and
      protein have discrepant effects on the release of PYY, but not ghrelin. When
      considered with our previous findings, it appears that, with the exception of
      ghrelin, the energy intake-suppressant effects of lipid and protein are mediated
      by different mechanisms. 

PMID- 25568081
TI  - High prevalence of hospitalisation for asthma in a population-based paediatric
      sample.

PMID- 25568082
TI  - In vivo, Argonaute-bound microRNAs exist predominantly in a reservoir of low
      molecular weight complexes not associated with mRNA.
AB  - MicroRNAs repress mRNA translation by guiding Argonaute proteins to partially
      complementary binding sites, primarily within the 3' untranslated region (UTR) of
      target mRNAs. In cell lines, Argonaute-bound microRNAs exist mainly in high
      molecular weight RNA-induced silencing complexes (HMW-RISC) associated with
      target mRNA. Here we demonstrate that most adult tissues contain reservoirs of
      microRNAs in low molecular weight RISC (LMW-RISC) not bound to mRNA, suggesting
      that these microRNAs are not actively engaged in target repression. Consistent
      with this observation, the majority of individual microRNAs in primary T cells
      were enriched in LMW-RISC. During T-cell activation, signal transduction through
      the phosphoinositide-3 kinase-RAC-alpha serine/threonine-protein kinase
      mechanistic target of rapamycin pathway increased the assembly of microRNAs into
      HMW-RISC, enhanced expression of the glycine-tryptophan protein of 182 kDa, an
      essential component of HMW-RISC, and improved the ability of microRNAs to repress
      partially complementary reporters, even when expression of targeting microRNAs
      did not increase. Overall, data presented here demonstrate that microRNA-mediated
      target repression in nontransformed cells depends not only on abundance of
      specific microRNAs, but also on regulation of RISC assembly by intracellular
      signaling. 

PMID- 25568083
TI  - Multiaddressable molecular rectangles with reversible host-guest interactions:
      modulation of pH-controlled guest release and capture.
AB  - A series of multiaddressable platinum(II) molecular rectangles with different
      rigidities and cavity sizes has been synthesized by endcapping the U-shaped
      diplatinum(II) terpyridine moiety with various bis-alkynyl ligands. The studies
      of the host-guest association with various square planar platinum(II),
      palladium(II), and gold(III) complexes and the related low-dimensional gold(I)
      complexes, most of which are potential anticancer therapeutics, have been
      performed. Excellent guest confinement and selectivity of the rectangular
      architecture have been shown. Introduction of pH-responsive functionalities to
      the ligand backbone generates multifunctional molecular rectangles that exhibit
      reversible guest release and capture on the addition of acids and bases,
      indicating their potential in controlled therapeutics delivery on pH modulation.
      The reversible host-guest interactions are found to be strongly perturbed by
      metal-metal and pi-pi interactions and to a certain extent, electrostatic
      interactions, giving rise to various spectroscopic changes depending on the
      nature of the guest molecules. Their binding mode and thermodynamic parameters
      have been determined by 2D NMR and van't Hoff analysis and supported by
      computational study. 

PMID- 25568084
TI  - Inference for dynamic and latent variable models via iterated, perturbed Bayes
      maps.
AB  - Iterated filtering algorithms are stochastic optimization procedures for latent
      variable models that recursively combine parameter perturbations with latent
      variable reconstruction. Previously, theoretical support for these algorithms has
      been based on the use of conditional moments of perturbed parameters to
      approximate derivatives of the log likelihood function. Here, a theoretical
      approach is introduced based on the convergence of an iterated Bayes map. An
      algorithm supported by this theory displays substantial numerical improvement on
      the computational challenge of inferring parameters of a partially observed
      Markov process. 

PMID- 25568086
TI  - Reconstructing pathogen evolution from the ruins.

PMID- 25568085
TI  - A chemiosmotic mechanism of symport.
AB  - Lactose permease (LacY), a paradigm for the largest family of membrane transport
      proteins, catalyzes the coupled translocation of a galactoside and an H(+) across
      the Escherichia coli membrane (galactoside/H(+) symport). Initial X-ray
      structures reveal N- and C-terminal domains, each with six largely irregular
      transmembrane helices surrounding an aqueous cavity open to the cytoplasm.
      Recently, a structure with a narrow periplasmic opening and an occluded
      galactoside was obtained, confirming many observations and indicating that sugar
      binding involves induced fit. LacY catalyzes symport by an alternating access
      mechanism. Experimental findings garnered over 45 y indicate the following: (i)
      The limiting step for lactose/H(+) symport in the absence of the H(+)
      electrochemical gradient (?uH+) is deprotonation, whereas in the presence of
      ?uH+, the limiting step is opening of apo LacY on the other side of the membrane;
      (ii) LacY must be protonated to bind galactoside (the pK for binding is ~10.5);
      (iii) galactoside binding and dissociation, not ?uH+, are the driving forces for
      alternating access; (iv) galactoside binding involves induced fit, causing
      transition to an occluded intermediate that undergoes alternating access; (v)
      galactoside dissociates, releasing the energy of binding; and (vi) Arg302 comes
      into proximity with protonated Glu325, causing deprotonation. Accumulation of
      galactoside against a concentration gradient does not involve a change in Kd for
      sugar on either side of the membrane, but the pKa (the affinity for H(+))
      decreases markedly. Thus, transport is driven chemiosmotically but, contrary to
      expectation, ?uH+ acts kinetically to control the rate of the process. 

PMID- 25568087
TI  - Impact synthesis of the RNA bases.

PMID- 25568089
TI  - Mass, energy and material balances of SRF production process. Part 3: solid
      recovered fuel produced from municipal solid waste.
AB  - This is the third and final part of the three-part article written to describe
      the mass, energy and material balances of the solid recovered fuel production
      process produced from various types of waste streams through mechanical
      treatment. This article focused the production of solid recovered fuel from
      municipal solid waste. The stream of municipal solid waste used here as an input
      waste material to produce solid recovered fuel is energy waste collected from
      households of municipality. This article presents the mass, energy and material
      balances of the solid recovered fuel production process. These balances are based
      on the proximate as well as the ultimate analysis and the composition
      determination of various streams of material produced in a solid recovered fuel
      production plant. All the process streams are sampled and treated according to
      CEN standard methods for solid recovered fuel. The results of the mass balance of
      the solid recovered fuel production process showed that 72% of the input waste
      material was recovered in the form of solid recovered fuel; 2.6% as ferrous
      metal, 0.4% as non-ferrous metal, 11% was sorted as rejects material, 12% as fine
      faction and 2% as heavy fraction. The energy balance of the solid recovered fuel
      production process showed that 86% of the total input energy content of input
      waste material was recovered in the form of solid recovered fuel. The remaining
      percentage (14%) of the input energy was split into the streams of reject
      material, fine fraction and heavy fraction. The material balances of this process
      showed that mass fraction of paper and cardboard, plastic (soft) and wood
      recovered in the solid recovered fuel stream was 88%, 85% and 90%, respectively,
      of their input mass. A high mass fraction of rubber material, plastic (PVC
      plastic) and inert (stone/rock and glass particles) was found in the reject
      material stream. 

PMID- 25568088
TI  - Loss of autophagy causes a synthetic lethal deficiency in DNA repair.
AB  - (Macro)autophagy delivers cellular constituents to lysosomes for degradation.
      Although a cytoplasmic process, autophagy-deficient cells accumulate genomic
      damage, but an explanation for this effect is currently unclear. We report here
      that inhibition of autophagy causes elevated proteasomal activity leading to
      enhanced degradation of checkpoint kinase 1 (Chk1), a pivotal factor for the
      error-free DNA repair process, homologous recombination (HR). We show that loss
      of autophagy critically impairs HR and that autophagy-deficient cells accrue
      micronuclei and sub-G1 DNA, indicators of diminished genomic integrity. Moreover,
      due to impaired HR, autophagy-deficient cells are hyperdependent on nonhomologous
      end joining (NHEJ) for repair of DNA double-strand breaks. Consequently,
      inhibition of NHEJ following DNA damage in the absence of autophagy results in
      persistence of genomic lesions and rapid cell death. Because autophagy deficiency
      occurs in several diseases, these findings constitute an important link between
      autophagy and DNA repair and highlight a synthetic lethal strategy to kill
      autophagy-deficient cells. 

PMID- 25568090
TI  - Effective solidification/stabilisation of mercury-contaminated wastes using
      zeolites and chemically bonded phosphate ceramics.
AB  - In this study, two kinds of zeolites materials (natural zeolite and thiol
      functionalised zeolite) were added to the chemically bonded phosphate ceramic
      processes to treat mercury-contaminated wastes. Strong promotion effects of
      zeolites (natural zeolite and thiol-functionalised zeolite) on the stability of
      mercury in the wastes were obtained and these technologies showed promising
      advantages toward the traditional Portland cement process, i.e. using Portland
      cement as a solidification agent and natural or thiol-functionalised zeolite as a
      stabilisation agent. Not only is a high stabilisation efficiency (lowered the
      Toxicity Characteristic Leaching Procedure Hg by above 10%) obtained, but also a
      lower dosage of solidification (for thiol-functionalised zeolite as stabilisation
      agent, 0.5 g g(-1) and 0.7 g g(-1) for chemically bonded phosphate ceramic and
      Portland cement, respectively) and stabilisation agents (for natural zeolite as
      stabilisation agent, 0.35 g g(-1) and 0.4 g g(-1) for chemically bonded phosphate
      ceramic and Portland cement, respectively) were used compared with the Portland
      cement process. Treated by thiol-functionalised zeolite and chemically bonded
      phosphate ceramic under optimum parameters, the waste containing 1500 mg Hg kg(
      1) passed the Toxicity Characteristic Leaching Procedure test. Moreover,
      stabilisation/solidification technology using natural zeolite and chemically
      bonded phosphate ceramic also passed the Toxicity Characteristic Leaching
      Procedure test (the mercury waste containing 625 mg Hg kg(-1)). Moreover, the
      presence of chloride and phosphate did not have a negative effect on the
      chemically bonded phosphate ceramic/thiol-functionalised zeolite treatment
      process; thus, showing potential for future application in treatment of
      'difficult-to-manage' mercury-contaminated wastes or landfill disposal with high
      phosphate and chloride content.

PMID- 25568091
TI  - Epidemiology and laboratory characteristics of Trichomonas vaginalis infection in
      Croatian men with and without urethritis syndrome: a case-control study.
AB  - OBJECTIVES: The main objective of this study is to determine the prevalence of
      trichomoniasis in men with and without symptoms of urethritis, with concomitant
      analysis of sociodemographic and behavioural specificities of both groups. Also,
      the objective is to evaluate laboratory methods used in the diagnostics of this
      parasitic disease. METHODS: A total of 500 men with and 200 without urethritis
      symptoms were included in the study. Every respondent filled out a questionnaire
      asking for some general data, specific information about habits, sexual behaviour
      and symptoms. Sediment of first void urine was analysed by wet mount microscopy,
      cultivation in Diamond's medium and real-time PCR. RESULTS: In the symptomatic
      group, Trichomonas vaginalis infection was documented in 2.4% of respondents by
      wet mount microscopy, in 4.8% by cultivation and in 8.2% by real-time PCR. In the
      asymptomatic group, infection was proven using the same methods in 1.0%, 1.5% and
      2.0% of the respondents, respectively. Trichomoniasis prevalence was
      statistically significantly higher in the respondents manifesting urethritis
      symptoms when cultivation (chi2=4.20, p=0.041) and real-time PCR (chi2=9.20,
      p=0.002) were used. Several epidemiological risk factors were identified, and
      greater sensitivity of real-time PCR was found in comparison with microscopy and
      culture. CONCLUSIONS: Trichomonas infection was statistically more frequent in
      men with urethritis syndrome. Assuming that the samples found positive by any
      laboratory technique are truly positive, it can be concluded that the real-time
      PCR showed the greatest sensitivity of all the methods used in this study.

PMID- 25568092
TI  - Suspension of accrual in phase II cancer clinical trials.
AB  - PURPOSE: Phase II cancer clinical trial designs commonly incorporate an interim
      analysis for lack of efficacy. To strictly and ethically implement such designs,
      one should suspend accrual in cases where pending patient outcomes can affect
      early termination decisions. This article aims to evaluate various options for
      accrual suspension and illustrate how the suspension strategy affects operating
      characteristics of the trial. METHODS: We define a strict suspension strategy for
      determining whether one should continue, suspend, or restart accrual at any point
      within the trial. The strategy is compared to a naive implementation of
      suspension and a strategy of no suspension. We evaluate the methods' operating
      characteristics by simulation. RESULTS: The suspension strategy has little effect
      on type I error, power, and early termination probability. Methods that involve
      stricter suspension policies generally lead to smaller but longer trials.
      Differences across strategies are substantial when the ratio of enrollment rate
      to outcome availability rate is high. CONCLUSION: The suspension strategy is most
      relevant in trials that accrue rapidly and require lengthy observation of each
      subject. The choice of suspension strategy involves a tradeoff between the cost
      of implementing a potentially complex suspension algorithm in real time versus
      the cost of enrolling more patients and exposing them to a potentially toxic and
      ineffective treatment regimen.

PMID- 25568093
TI  - From Infertility to Successful Third-Party Reproduction: The Trajectory of Greek
      Women.
AB  - The purpose of our phenomenological hermeneutic study was to explore the lived
      experiences of Greek infertile women who achieve a pregnancy through the use of
      sperm, oocyte, or embryo donation or surrogate motherhood. Semistructured
      interviews were conducted with 15 infertile women. Findings suggest that
      conceiving a child through assisted reproductive technologies (ART) is lived as a
      highly distressing experience, comprising long waiting periods for medical
      results, several failed attempts, and treatment options with uncertain outcomes.
      The analysis of women's accounts revealed a constitutive pattern, journeying
      between hope and despair, and three associated themes: (a) coping with
      uncertainty and treatment failures, (b) exploring options and decision making,
      and (c) being supported by spouse and professionals. Findings illuminate the
      specific meaning-based coping processes, decision-making patterns, and sources of
      support that help women who pursue treatment until they give birth to a child, to
      manage highly stressful situations and critical decisions. 

PMID- 25568094
TI  - Gender and Workplace Bullying: Men's Experiences of Surviving Bullying at Work.
AB  - Although men are targets of workplace bullying, there is limited research focused
      on their experiences. To address this gap, we used a qualitative grounded theory
      approach and interviewed a community sample of 20 Atlantic Canadian men to
      explore and explain their experiences of, and responses to, bullying. The main
      problem identified by men was a lack of workplace support to address and resolve
      the bullying, a challenge named abandonment. Men addressed this problem by
      surviving, a process that involved efforts to manage persistent bullying and the
      associated consequences. Men experienced physical, emotional, and social health
      consequences and, contrary to prevailing assumptions related to men's help
      seeking behaviors, men want support and many sought help to address the problem
      and its consequences. Responses to abandonment and the associated consequences
      varied according to a number of factors including gender and highlight the need
      for research aimed at understanding the gendered nature of bullying. 

PMID- 25568095
TI  - Ambulatory fall-risk assessment: amount and quality of daily-life gait predict
      falls in older adults.
AB  - BACKGROUND: Ambulatory measurements of trunk accelerations can provide valuable
      information on the amount and quality of daily-life activities and contribute to
      the identification of individuals at risk of falls. We compared associations
      between retrospective and prospective falls with potential risk factors as
      measured by daily-life accelerometry. In addition, we investigated predictive
      value of these parameters for 6-month prospective falls. METHODS: One week of
      trunk accelerometry (DynaPort MoveMonitor) was obtained in 169 older adults (mean
      age 75). The amount of daily activity and quality of gait were determined and
      validated questionnaires on fall-risk factors, grip strength, and trail making
      test were obtained. Six-month fall incidence was obtained retrospectively by
      recall and prospectively by fall diaries and monthly telephone contact. RESULTS:
      Among all participants, 35.5% had a history of >=1 falls and 34.9% experienced
      >=1 falls during 6-month follow-up. Logistic regressions showed that
      questionnaires, grip strength, and trail making test, as well as the amount and
      quality of gait, were significantly associated with falls. Significant
      associations differed between retrospective and prospective analyses although
      odds ratios indicated similar patterns. Predictive ability based on
      questionnaires, grip strength, and trail making test (area under the curve .68)
      improved substantially by accelerometry-derived parameters of the amount of gait
      (number of strides), gait quality (complexity, intensity, and smoothness), and
      their interactions (area under the curve .82). CONCLUSIONS: Daily-life
      accelerometry contributes substantially to the identification of individuals at
      risk of falls, and can predict falls in 6 months with good accuracy.

PMID- 25568096
TI  - Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence,
      MicroRNA Expression Profiles, and Comparison With In Vivo Models.
AB  - Our purpose was to evaluate long-term neuroglial cocultures as a model for
      investigating senescence in the nervous system and to assess its similarities
      with in vivo models. To this aim, we maintained the cultures from 15 days in
      vitro (mature cultures) up to 27 days in vitro (senescent cultures), measuring
      senescence-associated, neuronal, dendritic, and astrocytic markers. Whole
      microRNA expression profiles were compared with those measured in the cortex of
      18- and 24-month-old C57Bl/6J aged mice and of transgenic TgCRND8 mice, a model
      of amyloid-beta deposition. Neuroglial cocultures displayed features of cellular
      senescence (increased senescence-associated-beta-galactosidase activity,
      oxidative stress, gamma-H2AX expression, IL-6 production, astrogliosis) that were
      concentration dependently counteracted by the antiaging compound resveratrol (1-5
      uM). Among the 1,080 microRNAs analyzed, 335 were downregulated or absent in 27
      compared with 15 days in vitro and resveratrol reversed this effect. A
      substantial overlapping was found between age-associated changes in microRNA
      expression profiles in vitro and in TgCRND8 mice but not in physiologically aged
      mice, indicating that this culture model displays more similarities with
      pathological than physiological brain aging. Our results demonstrate that
      neuroglial cocultures aged in vitro can be useful for investigating the cellular
      and molecular mechanisms of brain aging and for preliminary testing of protective
      compounds. 

PMID- 25568098
TI  - Considering the impact of large-scale network interactions on cognitive control.

PMID- 25568097
TI  - Senescent Cells Contribute to the Physiological Remodeling of Aged Lungs.
AB  - Age-associated decline in organ function governs life span. We determined the
      effect of aging on lung function and cellular/molecular changes of 8- to 32-month
      old mice. Proteomic analysis of lung matrix indicated significant compositional
      changes with advanced age consistent with a profibrotic environment that leads to
      a significant increase in dynamic compliance and airway resistance. The excess of
      matrix proteins deposition was associated modestly with the activation of
      myofibroblasts and transforming growth factor-beta signaling pathway. More
      importantly, detection of senescent cells in the lungs increased with age and
      these cells contributed toward the excess extracellular matrix deposition
      observed in our aged mouse model and in elderly human samples. Mechanistic target
      of rapamycin (mTOR)/AKT activity was enhanced in aged mouse lungs compared with
      those from younger mice associated with the increased expression of the histone
      variant protein, MH2A, a marker for aging and potentially for senescence.
      Introduction in the mouse diet of rapamycin, significantly blocked the mTOR
      activity and limited the activation of myofibroblasts but did not result in a
      reduction in lung collagen deposition unless it was associated with prevention of
      cellular senescence. Together these data indicate that cellular senescence
      significantly contributes to the extracellular matrix changes associated with
      aging in a mTOR 1-dependent mechanism. 

PMID- 25568099
TI  - Demyelination causes adult CNS progenitors to revert to an immature state and
      express immune cues that support their migration.
AB  - The declining efficiency of myelin regeneration in individuals with multiple
      sclerosis has stimulated a search for ways by which it might be therapeutically
      enhanced. Here we have used gene expression profiling on purified murine
      oligodendrocyte progenitor cells (OPCs), the remyelinating cells of the adult
      CNS, to obtain a comprehensive picture of how they become activated after
      demyelination and how this enables them to contribute to remyelination. We find
      that adult OPCs have a transcriptome more similar to that of oligodendrocytes
      than to neonatal OPCs, but revert to a neonatal-like transcriptome when
      activated. Part of the activation response involves increased expression of two
      genes of the innate immune system, IL1beta and CCL2, which enhance the
      mobilization of OPCs. Our results add a new dimension to the role of the innate
      immune system in CNS regeneration, revealing how OPCs themselves contribute to
      the postinjury inflammatory milieu by producing cytokines that directly enhance
      their repopulation of areas of demyelination and hence their ability to
      contribute to remyelination. 

PMID- 25568100
TI  - Brg1-dependent chromatin remodelling is not essentially required during
      oligodendroglial differentiation.
AB  - Myelinating Schwann cells in the vertebrate peripheral nervous system rely on
      Brg1 (Smarca4) for terminal differentiation. Brg1 serves as central ATP
      hydrolyzing subunit of the chromatin remodelling BAF complexes and is recruited
      during myelination as part of these complexes by the transcription factor Sox10
      in Schwann cells. Here, we analyzed the role of Brg1 during development of
      myelinating oligodendrocytes in the CNS of the mouse. Following Brg1 deletion in
      oligodendrocyte precursors, these cells showed normal survival, proliferation,
      and migration. A mild but significant reduction in the number of oligodendrocytes
      with myelin gene expression in the absence of Brg1 points to a contribution to
      oligodendroglial differentiation but also shows that the role of Brg1 is much
      less prominent than during Schwann cell differentiation. Additionally, we failed
      to obtain evidence for a genetic interaction between Brg1 and Sox10 comparable
      with the one in Schwann cells. This argues that similarities exist between the
      regulatory networks and mechanisms in both types of myelinating glia but that the
      exact mode of action and the relevance of functional interactions differ,
      pointing to a surprising degree of variability in the control of myelination. 

PMID- 25568101
TI  - Caveolin-1 in the anterior cingulate cortex modulates chronic neuropathic pain
      via regulation of NMDA receptor 2B subunit.
AB  - Chronic pain is still a basic science and clinical challenge. Unraveling of the
      neurobiological mechanisms involved in chronic pain will offer novel targets for
      the development of therapeutic strategies. It is well known that central
      sensitization in the anterior cingulate cortex (ACC) plays a critical role in
      initiation, development, and maintenance of chronic pain. However, the underlying
      mechanisms still remain elusive. Here, we reported that caveolin-1 (Cav-1), a
      scaffolding protein in membrane rafts, was persistently upregulated and activated
      in the ACC neurons after chronic constriction injury (CCI) in mice. Knockdown or
      blocking of Cav-1 in the contralateral ACC to the injury side reversed CCI
      induced pain behavioral and neuronal sensitization and overexpression of Cav-1 in
      the ipsilateral ACC-induced pain behavior in the unaffected hindpaw. Furthermore,
      we found that Cav-1 directly binding with NMDA receptor 2B subunit (NR2B) and
      promotion of NR2B surface levels in the ACC contributed to modulation of chronic
      neuropathic pain. Disrupting the interaction of Cav-1 and NR2B through
      microinjection of a short peptide derived from the C-terminal of NR2B into the
      ACC exhibited a significant anti-nociception effect associated with decrease of
      surface NR2B expression. Moreover, Cav-1 increased intracellular Ca(2+)
      concentration and activated the ERK/CREB signaling pathway in an NR2B-dependent
      manner in the ACC. Our findings implicate that Cav-1 in the ACC neurons modulates
      chronic neuropathic pain via regulation of NR2B and subsequent activation of
      ERK/CREB signaling, suggesting a possible caveolin-mediated process would
      participate in neuronal transmission pathways implicated in pain modulation. 

PMID- 25568103
TI  - Sleep slow wave-related homo and heterosynaptic LTD of intrathalamic GABAAergic
      synapses: involvement of T-type Ca2+ channels and metabotropic glutamate
      receptors.
AB  - Slow waves of non-REM sleep are suggested to play a role in shaping synaptic
      connectivity to consolidate recently acquired memories and/or restore synaptic
      homeostasis. During sleep slow waves, both GABAergic neurons of the nucleus
      reticularis thalami (NRT) and thalamocortical (TC) neurons discharge high
      frequency bursts of action potentials mediated by low-threshold calcium spikes
      due to T-type Ca(2+) channel activation. Although such activity of the
      intrathalamic network characterized by high-frequency firing and calcium influx
      is highly suited to modify synaptic efficacy, very little is still known about
      its consequences on intrathalamic synapse strength. Combining in vitro
      electrophysiological recordings and calcium imaging, here we show that the
      inhibitory GABAergic synapses between NRT and TC neurons of the rat somatosensory
      nucleus develop a long-term depression (I-LTD) when challenged by a stimulation
      paradigm that mimics the thalamic network activity occurring during sleep slow
      waves. The mechanism underlying this plasticity presents unique features as it is
      both heterosynaptic and homosynaptic in nature and requires Ca(2+) entry
      selectively through T-type Ca(2+) channels and activation of the Ca(2+)-activated
      phosphatase, calcineurin. We propose that during slow-wave sleep the tight
      functional coupling between GABAA receptors, calcineurin, and T-type Ca(2+)
      channels will elicit LTD of the activated GABAergic synapses when coupled with
      concomitant activation of metabotropic glutamate receptors postsynaptic to
      cortical afferences. This I-LTD may be a key element involved in the reshaping of
      the somatosensory information pathway during sleep. 

PMID- 25568104
TI  - Pharmacogenetic excitation of dorsomedial prefrontal cortex restores fear
      prediction error.
AB  - Pavlovian conditioning involves encoding the predictive relationship between a
      conditioned stimulus (CS) and an unconditioned stimulus, so that synaptic
      plasticity and learning is instructed by prediction error. Here we used
      pharmacogenetic techniques to show a causal relation between activity of rat
      dorsomedial prefrontal cortex (dmPFC) neurons and fear prediction error. We
      expressed the excitatory hM3Dq designer receptor exclusively activated by a
      designer drug (DREADD) in dmPFC and isolated actions of prediction error by using
      an associative blocking design. Rats were trained to fear the visual CS (CSA) in
      stage I via pairings with footshock. Then in stage II, rats received compound
      presentations of visual CSA and auditory CS (CSB) with footshock. This prior fear
      conditioning of CSA reduced the prediction error during stage II to block fear
      learning to CSB. The group of rats that received AAV-hSYN-eYFP vector that was
      treated with clozapine-N-oxide (CNO; 3 mg/kg, i.p.) before stage II showed
      blocking when tested in the absence of CNO the next day. In contrast, the groups
      that received AAV-hSYN-hM3Dq and AAV-CaMKIIalpha-hM3Dq that were treated with CNO
      before stage II training did not show blocking; learning toward CSB was restored.
      This restoration of prediction error and fear learning was specific to the
      injection of CNO because groups that received AAV-hSYN-hM3Dq and AAV-CaMKIIalpha
      hM3Dq that were injected with vehicle before stage II training did show blocking.
      These effects were not attributable to the DREADD manipulation enhancing learning
      or arousal, increasing fear memory strength or asymptotic levels of fear
      learning, or altering fear memory retrieval. Together, these results identify a
      causal role for dmPFC in a signature of adaptive behavior: using the past to
      predict future danger and learning from errors in these predictions. 

PMID- 25568102
TI  - Imaging the awake visual cortex with a genetically encoded voltage indicator.
AB  - Genetically encoded voltage indicators (GEVIs) promise to reveal the membrane
      potential of genetically targeted neuronal populations through noninvasive,
      chronic imaging of large portions of cortical space. Here we test a promising
      GEVI in mouse cortex during wakefulness, a challenging condition due to large
      hemodynamic activity, and we introduce a straightforward projection method to
      separate a signal dominated by membrane voltage from a signal dominated by
      hemodynamic activity. We expressed VSFP-Butterfly 1.2 plasmid in layer 2/3
      pyramidal cells of visual cortex through electroporation in utero. We then used
      wide-field imaging with two cameras to measure both fluorophores of the indicator
      in response to visual stimuli. By taking weighted sums and differences of the two
      measurements, we obtained clear separation of hemodynamic and voltage signals.
      The hemodynamic signal showed strong heartbeat oscillations, superimposed on slow
      dynamics similar to blood oxygen level-dependent (BOLD) or "intrinsic" signals.
      The voltage signal had fast dynamics similar to neural responses measured
      electrically, and showed an orderly retinotopic mapping. We compared this voltage
      signal with calcium signals imaged in transgenic mice that express a calcium
      indicator (GCaMP3) throughout cortex. The voltage signal from VSFP had similar
      signal-to-noise ratios as the calcium signal, it was more immune to vascular
      artifacts, and it integrated over larger regions of visual space, which was
      consistent with its reporting mostly subthreshold activity rather than the
      spiking activity revealed by calcium signals. These results demonstrate that
      GEVIs provide a powerful tool to study the dynamics of neural populations at
      mesoscopic spatial scales in the awake cortex. 

PMID- 25568105
TI  - Temporal plasticity involved in recovery from manual dexterity deficit after
      motor cortex lesion in macaque monkeys.
AB  - The question of how intensive motor training restores motor function after brain
      damage or stroke remains unresolved. Here we show that the ipsilesional ventral
      premotor cortex (PMv) and perilesional primary motor cortex (M1) of rhesus
      macaque monkeys are involved in the recovery of manual dexterity after a lesion
      of M1. A focal lesion of the hand digit area in M1 was made by means of ibotenic
      acid injection. This lesion initially caused flaccid paralysis in the
      contralateral hand but was followed by functional recovery of hand movements,
      including precision grip, during the course of daily postlesion motor training.
      Brain imaging of regional cerebral blood flow by means of H2 (15)O-positron
      emission tomography revealed enhanced activity of the PMv during the early
      postrecovery period and increased functional connectivity within M1 during the
      late postrecovery period. The causal role of these areas in motor recovery was
      confirmed by means of pharmacological inactivation by muscimol during the
      different recovery periods. These findings indicate that, in both the remaining
      primary motor and premotor cortical areas, time-dependent plastic changes in
      neural activity and connectivity are involved in functional recovery from the
      motor deficit caused by the M1 lesion. Therefore, it is likely that the PMv, an
      area distant from the core of the lesion, plays an important role during the
      early postrecovery period, whereas the perilesional M1 contributes to functional
      recovery especially during the late postrecovery period. 

PMID- 25568106
TI  - Gene expression analyses identify Narp contribution in the development of L-DOPA
      induced dyskinesia.
AB  - In Parkinson's disease, long-term dopamine replacement therapy is complicated by
      the appearance of L-DOPA-induced dyskinesia (LID). One major hypothesis is that
      LID results from an aberrant transcriptional program in striatal neurons induced
      by L-DOPA and triggered by the activation of ERK. To identify these genes, we
      performed transcriptome analyses in the striatum in 6-hydroxydopamine-lesioned
      mice. A time course analysis (0-6 h after treatment with L-DOPA) identified an
      acute signature of 709 genes, among which genes involved in protein phosphatase
      activity were overrepresented, suggesting a negative feedback on ERK activation
      by l-DOPA. l-DOPA-dependent deregulation of 28 genes was blocked by pretreatment
      with SL327, an inhibitor of ERK activation, and 26 genes were found
      differentially expressed between highly and weakly dyskinetic animals after
      treatment with L-DOPA. The intersection list identified five genes: FosB, Th,
      Nptx2, Nedd4l, and Ccrn4l. Nptx2 encodes neuronal pentraxin II (or neuronal
      activity-regulated pentraxin, Narp), which is involved in the clustering of
      glutamate receptors. We confirmed increased Nptx2 expression after L-DOPA and its
      blockade by SL327 using quantitative RT-PCR in independent experiments. Using an
      escalating L-DOPA dose protocol, LID severity was decreased in Narp knock-out
      mice compared with their wild-type littermates or after overexpression of a
      dominant-negative form of Narp in the striatum. In conclusion, we have identified
      a molecular signature induced by L-DOPA in the dopamine-denervated striatum that
      is dependent on ERK and associated with LID. Here, we demonstrate the implication
      of one of these genes, Nptx2, in the development of LID.

PMID- 25568108
TI  - Persistent CaMKII activation mediates learning-induced long-lasting enhancement
      of synaptic inhibition.
AB  - Training rats in a particularly difficult olfactory-discrimination task results
      in acquisition of high skill to perform the task superbly, termed "rule learning"
      or "learning set." Such complex learning results in enhanced intrinsic neuronal
      excitability of piriform cortex pyramidal neurons, and in their excitatory
      synaptic interconnections. These changes, while subserving memory maintenance,
      must be counterbalanced by modifications that prevent overspreading of activity
      and uncontrolled synaptic strengthening. Indeed, we have previously shown that
      the average amplitude of GABAA-mediated miniature IPSCs (mIPSCs) in these neurons
      is enhanced for several days after learning, an enhancement mediated via a
      postsynaptic mechanism. To unravel the molecular mechanism of this long-term
      inhibition enhancement, we tested the role of key second-messenger systems in
      maintaining such long-lasting modulation. The calcium/calmodulin-dependent kinase
      II (CaMKII) blocker, KN93, significantly reduced the average mIPSC amplitude in
      neurons from trained rats only to the average pretraining level. A similar effect
      was obtained by the CaMKII peptide inhibitor, tatCN21. Such reduction resulted
      from decreased single-channel conductance and not in the number of activated
      channels. The PKC inhibitor, GF109203X, reduced the average mIPSC amplitude in
      neurons from naive, pseudo-trained, and trained animals, and the difference
      between the trained and control groups remained. Such reduction resulted from a
      decrease in the number of activated channels. The PKA inhibitor H89
      dihydrochloride did not affect the average mIPSC amplitude in neurons from any of
      the three groups. We conclude that learning-induced enhancement of GABAA-mediated
      synaptic inhibition is maintained by persistent CaMKII activation. 

PMID- 25568107
TI  - Diversity of glutamatergic synaptic strength in lateral prefrontal versus primary
      visual cortices in the rhesus monkey.
AB  - Understanding commonalities and differences in glutamatergic synaptic signaling
      is essential for understanding cortical functional diversity, especially in the
      highly complex primate brain. Previously, we have shown that spontaneous EPSCs
      differed markedly in layer 3 pyramidal neurons of two specialized cortical areas
      in the rhesus monkey, the high-order lateral prefrontal cortex (LPFC) and the
      primary visual cortex (V1). Here, we used patch-clamp recordings and confocal and
      electron microscopy to determine whether these distinct synaptic responses are
      due to differences in firing rates of presynaptic neurons and/or in the features
      of presynaptic or postsynaptic entities. As with spontaneous EPSCs, TTX
      insensitive (action potential-independent) miniature EPSCs exhibited
      significantly higher frequency, greater amplitude, and slower kinetics in LPFC
      compared with V1 neurons. Consistent with these physiological differences, LPFC
      neurons possessed higher densities of spines, and the mean width of large spines
      was greater compared with those on V1 neurons. Axospinous synapses in layers 2-3
      of LPFC had larger postsynaptic density surface areas and a higher proportion of
      large perforated synapses compared with V1. Axonal boutons in LPFC were also
      larger in volume and contained ~ 1.6* more vesicles than did those in V1.
      Further, LPFC had a higher density of AMPA GluR2 receptor labeling than V1. The
      properties of spines and synaptic currents of individual layer 3 pyramidal
      neurons measured here were significantly correlated, consistent with the idea
      that significantly more frequent and larger synaptic currents are likely due to
      more numerous, larger, and more powerful synapses in LPFC compared with V1.

PMID- 25568109
TI  - Mapping the stability of human brain asymmetry across five sex-chromosome
      aneuploidies.
AB  - The human brain displays stereotyped and early emerging patterns of cortical
      asymmetry in health. It is unclear if these asymmetries are highly sensitive to
      genetic and environmental variation or fundamental features of the brain that can
      survive severe developmental perturbations. To address this question, we mapped
      cortical thickness (CT) asymmetry in a group of genetically defined disorders
      known to impact CT development. Participants included 137 youth with one of five
      sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY
      (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls
      (80 female). In controls, we replicated previously reported rightward inferior
      frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal
      CT asymmetries were broadly preserved in all five SCA groups. However, we also
      detected foci of shifting CT asymmetry with aneuploidy, which fell almost
      exclusively within regions of significant CT asymmetry in controls. Specifically,
      X-chromosome aneuploidy accentuated normative rightward inferior frontal
      asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial
      prefrontal and lateral temporal asymmetries. These findings indicate that (1) the
      stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from
      developmental mechanisms that can withstand gross chromosomal aneuploidy and (2)
      X and Y chromosomes can exert focal, nonoverlapping and directionally opposed
      influences on CT asymmetry within cortical regions of significant asymmetry in
      health. Our study attests to the resilience of developmental mechanisms that
      support the global patterning of CT asymmetry in humans, and motivates future
      research into the molecular bases and functional consequences of sex chromosome
      dosage effects on CT asymmetry. 

PMID- 25568110
TI  - Circuit formation and function in the olfactory bulb of mice with reduced
      spontaneous afferent activity.
AB  - The type of neuronal activity required for circuit development is a matter of
      significant debate. We addressed this issue by analyzing the topographic
      organization of the olfactory bulb in transgenic mice engineered to have very
      little afferent spontaneous activity due to the overexpression of the inwardly
      rectifying potassium channel Kir2.1 in the olfactory sensory neurons (Kir2.1
      mice). In these conditions, the topography of the olfactory bulb was unrefined.
      Odor-evoked responses were readily recorded in glomeruli with reduced spontaneous
      afferent activity, although the functional maps were coarser than in controls and
      contributed to altered olfactory discrimination behavior. In addition,
      overexpression of Kir2.1 in adults induced a regression of the already refined
      connectivity to an immature (i.e., coarser) status. Our data suggest that
      spontaneous activity plays a critical role not only in the development but also
      in the maintenance of the topography of the olfactory bulb and in sensory
      information processing. 

PMID- 25568111
TI  - Methylphenidate and atomoxetine inhibit social play behavior through prefrontal
      and subcortical limbic mechanisms in rats.
AB  - Positive social interactions during the juvenile and adolescent phases of life,
      in the form of social play behavior, are important for social and cognitive
      development. However, the neural mechanisms of social play behavior remain
      incompletely understood. We have previously shown that methylphenidate and
      atomoxetine, drugs widely used for the treatment of attention-deficit
      hyperactivity disorder (ADHD), suppress social play in rats through a
      noradrenergic mechanism of action. Here, we aimed to identify the neural
      substrates of the play-suppressant effects of these drugs. Methylphenidate is
      thought to exert its effects on cognition and emotion through limbic
      corticostriatal systems. Therefore, methylphenidate was infused into prefrontal
      and orbitofrontal cortical regions as well as into several subcortical limbic
      areas implicated in social play. Infusion of methylphenidate into the anterior
      cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula
      inhibited social play, but not social exploratory behavior or locomotor activity.
      Consistent with a noradrenergic mechanism of action of methylphenidate, infusion
      of the noradrenaline reuptake inhibitor atomoxetine into these same regions also
      reduced social play. Methylphenidate administration into the prelimbic,
      medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal
      thalamus, or nucleus accumbens shell was ineffective. Our data show that the
      inhibitory effects of methylphenidate and atomoxetine on social play are mediated
      through a distributed network of prefrontal and limbic subcortical regions
      implicated in cognitive control and emotional processes. These findings increase
      our understanding of the neural underpinnings of this developmentally important
      social behavior, as well as the mechanism of action of two widely used treatments
      for ADHD. 

PMID- 25568112
TI  - Cortical state determines global variability and correlations in visual cortex.
AB  - The response of neurons in sensory cortex to repeated stimulus presentations is
      highly variable. To investigate the nature of this variability, we compared the
      spike activity of neurons in the primary visual cortex (V1) of cats with that of
      their afferents from lateral geniculate nucleus (LGN), in response to similar
      stimuli. We found variability to be much higher in V1 than in LGN. To investigate
      the sources of the additional variability, we measured the spiking activity of
      large V1 populations and found that much of the variability was shared across
      neurons: the variable portion of the responses of one neuron could be well
      predicted from the summed activity of the rest of the neurons. Variability thus
      mostly reflected global fluctuations affecting all neurons. The size and
      prevalence of these fluctuations, both in responses to stimuli and in ongoing
      activity, depended on cortical state, being larger in synchronized states than in
      more desynchronized states. Contrary to previous reports, these fluctuations
      invested the overall population, regardless of preferred orientation. The global
      fluctuations substantially increased variability in single neurons and
      correlations among pairs of neurons. Once this effect was removed, pairwise
      correlations were reduced and were similar regardless of cortical state. These
      results highlight the importance of cortical state in controlling cortical
      operation and can help reconcile previous studies, which differed widely in their
      estimate of neuronal variability and pairwise correlations. 

PMID- 25568113
TI  - Learning modifies odor mixture processing to improve detection of relevant
      components.
AB  - Honey bees have a rich repertoire of olfactory learning behaviors, and they
      therefore are an excellent model to study plasticity in olfactory circuits.
      Recent behavioral, physiological, and molecular evidence suggested that the
      antennal lobe, the first relay of the olfactory system in insects and analog to
      the olfactory bulb in vertebrates, is involved in associative and nonassociative
      olfactory learning. Here we use calcium imaging to reveal how responses across
      antennal lobe projection neurons change after association of an input odor with
      appetitive reinforcement. After appetitive conditioning to 1-hexanol, the
      representation of an odor mixture containing 1-hexanol becomes more similar to
      this odor and less similar to the background odor acetophenone. We then apply
      computational modeling to investigate how changes in synaptic connectivity can
      account for the observed plasticity. Our study suggests that experience-dependent
      modulation of inhibitory interactions in the antennal lobe aids perception of
      salient odor components mixed with behaviorally irrelevant background odors. 

PMID- 25568114
TI  - Distinct midbrain and habenula pathways are involved in processing aversive
      events in humans.
AB  - Emerging evidence implicates the midbrain dopamine system and its interactions
      with the lateral habenula in processing aversive information and learning to
      avoid negative outcomes. We examined neural responses to unexpected, aversive
      events using methods specialized for imaging the midbrain and habenula in humans.
      Robust activation to aversive relative to neutral events was observed in the
      habenula and two regions within the ventral midbrain: one located within the
      ventral tegmental area (VTA) and the other in the substantia nigra (SN). Aversive
      processing increased functional connectivity between the VTA and the habenula,
      putamen, and medial prefrontal cortex, whereas the SN exhibited a different
      pattern of functional connectivity. Our findings provide evidence for a network
      comprising the VTA and SN, the habenula, and mesocorticolimbic structures that
      supports processing aversive events in humans. 

PMID- 25568115
TI  - The neural substrate for binaural masking level differences in the auditory
      cortex.
AB  - The binaural masking level difference (BMLD) is a phenomenon whereby a signal
      that is identical at each ear (S0), masked by a noise that is identical at each
      ear (N0), can be made 12-15 dB more detectable by inverting the waveform of
      either the tone or noise at one ear (Spi, Npi). Single-cell responses to BMLD
      stimuli were measured in the primary auditory cortex of urethane-anesthetized
      guinea pigs. Firing rate was measured as a function of signal level of a 500 Hz
      pure tone masked by low-passed white noise. Responses were similar to those
      reported in the inferior colliculus. At low signal levels, the response was
      dominated by the masker. At higher signal levels, firing rate either increased or
      decreased. Detection thresholds for each neuron were determined using signal
      detection theory. Few neurons yielded measurable detection thresholds for all
      stimulus conditions, with a wide range in thresholds. However, across the entire
      population, the lowest thresholds were consistent with human psychophysical
      BMLDs. As in the inferior colliculus, the shape of the firing-rate versus signal
      level functions depended on the neurons' selectivity for interaural time
      difference. Our results suggest that, in cortex, BMLD signals are detected from
      increases or decreases in the firing rate, consistent with predictions of cross
      correlation models of binaural processing and that the psychophysical detection
      threshold is based on the lowest neural thresholds across the population. 

PMID- 25568117
TI  - Fgf-signaling-dependent Sox9a and Atoh1a regulate otic neural development in
      zebrafish.
AB  - Fibroblast growth factors (Fgfs) play important roles in developmental processes
      of the inner ear, including the ontogeny of the statoacoustic ganglia (SAG) and
      hair cells. However, the detailed genetic mechanism(s) underlying Fgf/Fgfr
      dependent otic neural development remains elusive. Using conditional genetic
      approaches and inhibitory small molecules, we have revealed that Fgfr-PI3K/Akt
      signaling is mainly responsible for zebrafish SAG development and have determined
      that Sox9a and Atoh1a act downstream of Fgfr-Akt signaling to specify and/or
      maintain the otic neuron fate during the early segmentation stage. Sox9a and
      Atoh1a coregulate numerous downstream factors identified through our ChIP-seq
      analyses, including Tlx2 and Eya2. Fgfr-Erk1/2 signaling contributes to
      ultricular hair cell development during a critical period between 9 and 15 hours
      postfertilization. Our work reveals that a genetic network of the previously
      known sensory determinant Atoh1 and the neural crest determinant Sox9 plays
      critical roles in SAG development. These newly uncovered roles for Atoh1and Sox9
      in zebrafish otic development may be relevant to study in other species. 

PMID- 25568116
TI  - Itk signals promote neuroinflammation by regulating CD4+ T-cell activation and
      trafficking.
AB  - Here we demonstrate that interleukin-2-inducible T-cell kinase (Itk) signaling in
      cluster of differentiation 4-positive (CD4(+)) T cells promotes experimental
      autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS).
      We show that Itk(-/-) mice exhibit reduced disease severity, and transfer of Itk(
      /-) CD4(+) T cells into T cell-deficient recipients results in lower disease
      severity. We observed a significant reduction of CD4(+) T cells in the CNS of
      Itk(-/-) mice or recipients of Itk(-/-) CD4(+) T cells during EAE, which is
      consistent with attenuated disease. Itk(-/-) CD4(+) T cells exhibit defective
      response to myelin antigen stimulation attributable to displacement of
      filamentous actin from the CD4(+) coreceptor. This results in inadequate
      transmigration of Itk(-/-) CD4(+) T cells into the CNS and across brain
      endothelial barriers in vitro. Finally, Itk(-/-) CD4(+) T cells show significant
      reduction in production of T-helper 1 (Th1) and Th17 cytokines and exhibit skewed
      T effector/T regulatory cell ratios. These results indicate that signaling by Itk
      promotes autoimmunity and CNS inflammation, suggesting that it may be a viable
      target for treatment of MS. 

PMID- 25568118
TI  - Saccade planning evokes topographically specific activity in the dorsal and
      ventral streams.
AB  - Saccade planning may invoke spatially-specific feedback signals that bias early
      visual activity in favor of top-down goals. We tested this hypothesis by
      measuring cortical activity at the early stages of the dorsal and ventral visual
      processing streams. Human subjects maintained saccade plans to (prosaccade) or
      away (antisaccade) from a spatial location over long memory-delays. Results show
      that cortical activity persists in early visual cortex at the retinotopic
      location of upcoming saccade goals. Topographically specific activity persists as
      early as V1, and activity increases along both dorsal (V3A/B, IPS0) and ventral
      (hV4, VO1) visual areas. Importantly, activity persists when saccade goals are
      available only via working memory and when visual targets and saccade goals are
      spatially disassociated. We conclude that top-down signals elicit retinotopically
      specific activity in visual cortex both in the dorsal and ventral streams. Such
      activity may underlie mechanisms that prioritize locations of task-relevant
      objects. 

PMID- 25568119
TI  - Spatial and temporal characteristics of error-related activity in the human
      brain.
AB  - A number of studies have focused on the role of specific brain regions, such as
      the dorsal anterior cingulate cortex during trials on which participants make
      errors, whereas others have implicated a host of more widely distributed regions
      in the human brain. Previous work has proposed that there are multiple cognitive
      control networks, raising the question of whether error-related activity can be
      found in each of these networks. Thus, to examine error-related activity broadly,
      we conducted a meta-analysis consisting of 12 tasks that included both error and
      correct trials. These tasks varied by stimulus input (visual, auditory), response
      output (button press, speech), stimulus category (words, pictures), and task type
      (e.g., recognition memory, mental rotation). We identified 41 brain regions that
      showed a differential fMRI BOLD response to error and correct trials across a
      majority of tasks. These regions displayed three unique response profiles: (1)
      fast, (2) prolonged, and (3) a delayed response to errors, as well as a more
      canonical response to correct trials. These regions were found mostly in several
      control networks, each network predominantly displaying one response profile. The
      one exception to this "one network, one response profile" observation is the
      frontoparietal network, which showed prolonged response profiles (all in the
      right hemisphere), and fast profiles (all but one in the left hemisphere). We
      suggest that, in the place of a single localized error mechanism, these findings
      point to a large-scale set of error-related regions across multiple systems that
      likely subserve different functions. 

PMID- 25568121
TI  - Altered sensory experience exacerbates stable dendritic spine and synapse loss in
      a mouse model of Huntington's disease.
AB  - A key question in Huntington's disease (HD) is what underlies the early cognitive
      deficits that precede the motor symptoms and the characteristic neuronal death
      observed in HD. The mechanisms underlying cognitive symptoms in HD remain
      unknown. Postmortem HD brain and animal model studies demonstrate pathologies in
      dendritic spines and abnormal synaptic plasticity before motor symptoms and
      neurodegeneration. Experience-dependent synaptic plasticity caused by mechanisms
      such as LTP or novel sensory experience potentiates synaptic strength, enhances
      new dendritic spine formation and stabilization, and may contribute to normal
      cognitive processes, such as learning and memory. We have previously reported
      that under baseline conditions (without any sensory manipulation) neuronal
      circuitry in HD (R6/2 mouse model) was highly unstable, which led to a
      progressive loss of persistent spines in these mice, and that mutant huntingtin
      was directly involved in the process. Here, we investigated whether pathological
      processes of HD interfere with the normal experience-dependent plasticity of
      dendritic spines in the R6/2 model. Six weeks of two-photon in vivo imaging
      before and after whisker trimming revealed that sensory deprivation exacerbates
      loss of persistent-type, stable spines in R6/2 mice compared with wild-type
      littermates. In addition, sensory deprivation leads to impaired transformation of
      newly generated spines into persistent spines in R6/2 mice. As a consequence,
      reduced synaptic density and decreased PSD-95 protein levels are evident in their
      barrel cortical neurons. These data suggest that mutant huntingtin is implicated
      in maladaptive synaptic plasticity, which could be one of the plausible
      mechanisms underlying early cognitive deficits in HD. 

PMID- 25568120
TI  - Early-course unmedicated schizophrenia patients exhibit elevated prefrontal
      connectivity associated with longitudinal change.
AB  - Strong evidence implicates prefrontal cortex (PFC) as a major source of
      functional impairment in severe mental illness such as schizophrenia. Numerous
      schizophrenia studies report deficits in PFC structure, activation, and
      functional connectivity in patients with chronic illness, suggesting that
      deficient PFC functional connectivity occurs in this disorder. However, the PFC
      functional connectivity patterns during illness onset and its longitudinal
      progression remain uncharacterized. Emerging evidence suggests that early-course
      schizophrenia involves increased PFC glutamate, which might elevate PFC
      functional connectivity. To test this hypothesis, we examined 129 non-medicated,
      human subjects diagnosed with early-course schizophrenia and 106 matched healthy
      human subjects using both whole-brain data-driven and hypothesis-driven PFC
      analyses of resting-state fMRI. We identified increased PFC connectivity in early
      course patients, predictive of symptoms and diagnostic classification, but less
      evidence for "hypoconnectivity." At the whole-brain level, we observed
      "hyperconnectivity" around areas centered on the default system, with modest
      overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a
      subset of the sample followed longitudinally (n = 25), which also predicted
      immediate symptom improvement. Biologically informed computational modeling
      implicates altered overall connection strength in schizophrenia. The initial
      hyperconnectivity, which may decrease longitudinally, could have prognostic and
      therapeutic implications. 

PMID- 25568122
TI  - Motor origin of precise synaptic inputs onto forebrain neurons driving a skilled
      behavior.
AB  - Sensory feedback is crucial for learning and performing many behaviors, but its
      role in the execution of complex motor sequences is poorly understood. To address
      this, we consider the forebrain nucleus HVC in the songbird, which contains the
      premotor circuitry for song production and receives multiple convergent sensory
      inputs. During singing, projection neurons within HVC exhibit precisely timed
      synaptic events that may represent the ongoing motor program or song-related
      sensory feedback. To distinguish between these possibilities, we recorded the
      membrane potential from identified HVC projection neurons in singing zebra
      finches. External auditory perturbations during song production did not affect
      synaptic inputs in these neurons. Furthermore, the systematic removal of three
      sensory feedback streams (auditory, proprioceptive, and vagal) did not alter the
      frequency or temporal precision of synaptic activity observed. These findings
      support a motor origin for song-related synaptic events and suggest an updated
      circuit model for generating behavioral sequences. 

PMID- 25568123
TI  - Extracellular glutamate exposure facilitates group I mGluR-mediated
      epileptogenesis in the hippocampus.
AB  - Stimulation of group I mGluRs elicits several forms of translation-dependent
      neuronal plasticity including epileptogenesis. The translation process underlying
      plasticity induction is controlled by repressors including the fragile X mental
      retardation protein (FMRP). In the absence of FMRP-mediated repression, a
      condition that occurs in a mouse model (Fmr1(-/-)) of fragile X syndrome, group I
      mGluR-activated translation is exaggerated causing enhanced seizure propensity.
      We now show that glutamate exposure (10 MUm for 30 min) reduced FMRP levels in
      wild-type mouse hippocampal slices. Downregulation of FMRP was dependent on group
      I mGluR activation and was blocked by a proteasome inhibitor (MG-132). Following
      glutamate exposure, synaptic stimulation induced prolonged epileptiform
      discharges with properties similar to those observed in Fmr1(-/-) preparations.
      In both cases, prolonged epileptiform discharges were blocked by group I mGluR
      antagonists (LY367385 + MPEP) and their induction was prevented by protein
      synthesis inhibitor (anisomycin). The results suggest that stimulation of group I
      mGluRs during glutamate exposure caused proteolysis of FMRP. Reduction of FMRP
      led to enhanced synaptic group I mGluR-mediated translation. Elevated translation
      facilitated the recruitment of group I mGluR-mediated prolonged epileptiform
      discharges. 

PMID- 25568124
TI  - Stress induces the danger-associated molecular pattern HMGB-1 in the hippocampus
      of male Sprague Dawley rats: a priming stimulus of microglia and the NLRP3
      inflammasome.
AB  - Exposure to acute and chronic stressors sensitizes the proinflammatory response
      of microglia to a subsequent immune challenge. However, the proximal signal by
      which stressors prime microglia remains unclear. Here, high mobility group box-1
      (HMGB-1) protein was explored as a potential mediator of stress-induced
      microglial priming and whether HMGB-1 does so via the nucleotide-binding domain,
      leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome.
      Exposure to 100 inescapable tail shocks (ISs) increased HMGB-1 and NLRP3 protein
      in the hippocampus and led isolated microglia to release HMGB-1 ex vivo. To
      determine whether HMGB-1 signaling is necessary for stress-induced sensitization
      of microglia, the HMGB-1 antagonist BoxA was injected into the cisterna magna
      before IS. Hippocampal microglia were isolated 24 h later and stimulated with LPS
      ex vivo to probe for stress-induced sensitization of proinflammatory responses.
      Previous IS potentiated gene expression of NLRP3 and proinflammatory cytokines to
      LPS, that is, microglia were sensitized. Treatment with BoxA abolished this
      effect. To determine whether HMGB-1 is sufficient to prime microglia, IS was
      replaced with intracerebral administration of disulfide or fully reduced HMGB-1.
      Intracerebral disulfide HMGB-1 mimicked the effect of the stressor, because
      microglia isolated from HMGB-1-treated rats expressed exaggerated NLRP3 and
      proinflammatory cytokine expression after LPS treatment, whereas fully reduced
      HMGB-1 had no effect. The present results suggest that the CNS innate immune
      system can respond to an acute stressor as if it were cellular damage, thereby
      releasing the danger signal HMGB-1 in the brain to prime microglia by acting on
      the NLRP3 inflammasome, in preparation for a later immune challenge. 

PMID- 25568126
TI  - Overexpression of the type 1 adenylyl cyclase in the forebrain leads to deficits
      of behavioral inhibition.
AB  - The type 1 adenylyl cyclase (AC1) is an activity-dependent, calcium-stimulated
      adenylyl cyclase expressed in the nervous system that is implicated in memory
      formation. We examined the locomotor activity, and impulsive and social behaviors
      of AC1+ mice, a transgenic mouse strain overexpressing AC1 in the forebrain. Here
      we report that AC1+ mice exhibit hyperactive behaviors and demonstrate increased
      impulsivity and reduced sociability. In contrast, AC1 and AC8 double knock-out
      mice are hypoactive, and exhibit increased sociability and reduced impulsivity.
      Interestingly, the hyperactivity of AC1+ mice can be corrected by valproate, a
      mood-stabilizing drug. These data indicate that increased expression of AC1 in
      the forebrain leads to deficits in behavioral inhibition. 

PMID- 25568125
TI  - Gene dosage in the dysbindin schizophrenia susceptibility network differentially
      affect synaptic function and plasticity.
AB  - Neurodevelopmental disorders arise from single or multiple gene defects. However,
      the way multiple loci interact to modify phenotypic outcomes remains poorly
      understood. Here, we studied phenotypes associated with mutations in the
      schizophrenia susceptibility gene dysbindin (dysb), in isolation or in
      combination with null alleles in the dysb network component Blos1. In humans, the
      Blos1 ortholog Bloc1s1 encodes a polypeptide that assembles, with dysbindin, into
      the octameric BLOC-1 complex. We biochemically confirmed BLOC-1 presence in
      Drosophila neurons, and measured synaptic output and complex adaptive behavior in
      response to BLOC-1 perturbation. Homozygous loss-of-function alleles of dysb,
      Blos1, or compound heterozygotes of these alleles impaired neurotransmitter
      release, synapse morphology, and homeostatic plasticity at the larval
      neuromuscular junction, and impaired olfactory habituation. This multiparameter
      assessment indicated that phenotypes were differentially sensitive to genetic
      dosages of loss-of-function BLOC-1 alleles. Our findings suggest that
      modification of a second genetic locus in a defined neurodevelopmental regulatory
      network does not follow a strict additive genetic inheritance, but rather,
      precise stoichiometry within the network determines phenotypic outcomes. 

PMID- 25568128
TI  - Bridging the gap between perceptual and cognitive perspectives on absolute pitch.
AB  - Absolute pitch (AP) refers to the rare ability to identify the chroma of a tone
      or to produce a specific pitch without reference to keyality (e.g., G or C).
      Previously, AP has been proposed to rely on the distinctive functional-anatomical
      architecture of the left auditory-related cortex (ARC), this specific trait
      possibly enabling an optimized early "categorical perception". In contrast,
      currently prevailing models of AP postulate that cognitive rather than perceptual
      processes, namely "pitch labeling" mechanisms, more likely constitute the bearing
      skeleton of AP. This associative memory component has previously been proposed to
      be dependent, among other mechanisms, on the recruitment of the left dorsolateral
      prefrontal cortex (DLPFC) as well as on the integrity of the left arcuate
      fasciculus, a fiber bundle linking the posterior supratemporal plane with the
      DLPFC. Here, we attempted to integrate these two apparently conflicting
      perspectives on AP, namely early "categorical perception" and "pitch labeling".
      We used electroencephalography and evaluated resting-state intracranial
      functional connectivity between the left ARC and DLPFC in a sample of musicians
      with and without AP. Results demonstrate significantly increased left-hemispheric
      theta phase synchronization in AP compared with non-AP musicians. Within the AP
      group, this specific electrophysiological marker was predictive of absolute
      hearing behavior and explained ~30% of variance. Thus, we propose that in AP
      subjects the tonal inputs and the corresponding mnemonic representations are
      tightly coupled in such a manner that the distinctive electrophysiological
      signature of AP can saliently be detected in only 3 min of resting-state
      measurements. 

PMID- 25568127
TI  - Chromatin landscape defined by repressive histone methylation during
      oligodendrocyte differentiation.
AB  - In many cell types, differentiation requires an interplay between extrinsic
      signals and transcriptional changes mediated by repressive and activating histone
      modifications. Oligodendrocyte progenitors (OPCs) are electrically responsive
      cells receiving synaptic input. The differentiation of these cells into
      myelinating oligodendrocytes is characterized by temporal waves of gene
      repression followed by activation of myelin genes and progressive decline of
      electrical responsiveness. In this study, we used chromatin isolated from rat
      OPCs and immature oligodendrocytes, to characterize the genome-wide distribution
      of the repressive histone marks, H3K9me3 and H3K27me3, during differentiation.
      Although both marks were present at the OPC stage, only H3K9me3 marks (but not
      H3K27me3) were found to be increased during differentiation, at genes related to
      neuronal lineage and regulation of membrane excitability. Consistent with these
      findings, the levels and activity of H3K9 methyltransferases (H3K9 HMT), but not
      H3K27 HMT, increased more prominently upon exposure to oligodendrocyte
      differentiating stimuli and were detected in stage-specific repressive protein
      complexes containing the transcription factors SOX10 or YY1. Silencing H3K9 HMT,
      but not H3K27 HMT, impaired oligodendrocyte differentiation and functionally
      altered the response of oligodendrocytes to electrical stimulation. Together,
      these results identify repressive H3K9 methylation as critical for gene
      repression during oligodendrocyte differentiation. 

PMID- 25568129
TI  - Combinatorial mutagenesis of the voltage-sensing domain enables the optical
      resolution of action potentials firing at 60 Hz by a genetically encoded
      fluorescent sensor of membrane potential.
AB  - ArcLight is a genetically encoded fluorescent voltage sensor using the voltage
      sensing domain of the voltage-sensing phosphatase from Ciona intestinalis that
      gives a large but slow-responding optical signal in response to changes in
      membrane potential (Jin et al., 2012). Fluorescent voltage sensors using the
      voltage-sensing domain from other species give faster yet weaker optical signals
      (Baker et al., 2012; Han et al., 2013). Sequence alignment of voltage-sensing
      phosphatases from different species revealed conserved polar and charged residues
      at 7 aa intervals in the S1-S3 transmembrane segments of the voltage-sensing
      domain, suggesting potential coil-coil interactions. The contribution of these
      residues to the voltage-induced optical signal was tested using a cassette
      mutagenesis screen by flanking each transmembrane segment with unique restriction
      sites to allow for the testing of individual mutations in each transmembrane
      segment, as well as combinations in all four transmembrane segments. Addition of
      a counter charge in S2 improved the kinetics of the optical response. A double
      mutation in the S4 domain dramatically reduced the slow component of the optical
      signal seen in ArcLight. Combining that double S4 mutant with the mutation in the
      S2 domain yielded a probe with kinetics <10 ms. Optimization of the linker
      sequence between S4 and the fluorescent protein resulted in a new ArcLight
      derived probe, Bongwoori, capable of resolving action potentials in a hippocampal
      neuron firing at 60 Hz. Additional manipulation of the voltage-sensing domain
      could potentially lead to fluorescent sensors capable of optically resolving
      neuronal inhibition and subthreshold synaptic activity. 

PMID- 25568130
TI  - cJun and CREB2 in the postsynaptic neuron contribute to persistent long-term
      facilitation at a behaviorally relevant synapse.
AB  - Basic region leucine zipper (bZIP) transcription factors regulate gene expression
      critical for long-term synaptic plasticity or neuronal excitability contributing
      to learning and memory. At sensorimotor synapses of Aplysia, changes in
      activation or expression of CREB1 and CREB2 in sensory neurons are required for
      long-term synaptic plasticity. However, it is unknown whether concomitant
      stimulus-induced changes in expression and activation of bZIP transcription
      factors in the postsynaptic motor neuron also contribute to persistent long-term
      facilitation (P-LTF). We overexpressed various forms of CREB1, CREB2, or cJun in
      the postsynaptic motor neuron L7 in cell culture to examine whether these factors
      contribute to P-LTF. P-LTF is evoked by 2 consecutive days of 5-HT applications
      (2 5-HT), while a transient form of LTF is produced by 1 day of 5-HT applications
      (1 5-HT). Significant increases in the expression of both cJun and CREB2 mRNA in
      L7 accompany P-LTF. Overexpressing each bZIP factor in L7 did not alter basal
      synapse strength, while coexpressing cJun and CREB2 in L7 evoked persistent
      increases in basal synapse strength. In contrast, overexpressing cJun and CREB2
      in sensory neurons evoked persistent decreases in basal synapse strength.
      Overexpressing wild-type cJun or CREB2, but not CREB1, in L7 can replace the
      second day of 5-HT applications in producing P-LTF. Reducing cJun activity in L7
      blocked P-LTF evoked by 2 5-HT. These results suggest that expression and
      activation of different bZIP factors in both presynaptic and postsynaptic neurons
      contribute to persistent change in synapse strength including stimulus-dependent
      long-term synaptic plasticity. 

PMID- 25568131
TI  - PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse
      models of fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the leading cause of both intellectual disability and
      autism resulting from a single gene mutation. Previously, we characterized
      cognitive impairments and brain structural defects in a Drosophila model of FXS
      and demonstrated that these impairments were rescued by treatment with
      metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented
      biochemical defect observed in fly and mouse FXS models and FXS patients is low
      cAMP levels. cAMP levels can be regulated by mGluR signaling. Herein, we
      demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate memory
      impairments and brain structural defects in the Drosophila model of fragile X.
      Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic
      treatment in the fragile X mouse model. We demonstrate that acute inhibition of
      PDE-4 by pharmacologic treatment in hippocampal slices rescues the enhanced mGluR
      dependent LTD phenotype observed in FXS mice. Additionally, we find that chronic
      treatment of FXS model mice, in adulthood, also restores the level of mGluR
      dependent LTD to that observed in wild-type animals. Translating the findings of
      successful pharmacologic intervention from the Drosophila model into the mouse
      model of FXS is an important advance, in that this identifies and validates PDE-4
      inhibition as potential therapeutic intervention for the treatment of individuals
      afflicted with FXS. 

PMID- 25568132
TI  - Expanded terminal fields of gustatory nerves accompany embryonic BDNF
      overexpression in mouse oral epithelia.
AB  - Brain-derived neurotrophic factor (BDNF) is expressed in gustatory epithelia and
      is required for gustatory neurons to locate and innervate their correct target
      during development. When BDNF is overexpressed throughout the lingual epithelium,
      beginning embryonically, chorda tympani fibers are misdirected and innervate
      inappropriate targets, leading to a loss of taste buds. The remaining taste buds
      are hyperinnervated, demonstrating a disruption of nerve/target matching in the
      tongue. We tested the hypothesis here that overexpression of BDNF peripherally
      leads to a disrupted terminal field organization of nerves that carry taste
      information to the brainstem. The chorda tympani, greater superficial petrosal,
      and glossopharyngeal nerves were labeled in adult wild-type (WT) mice and in
      adult mice in which BDNF was overexpressed (OE) to examine the volume and density
      of their central projections in the nucleus of the solitary tract. We found that
      the terminal fields of the chorda tympani and greater superficial petrosal nerves
      and overlapping fields that included these nerves in OE mice were at least 80%
      greater than the respective field volumes in WT mice. The shapes of terminal
      fields were similar between the two groups; however, the density and spread of
      labels were greater in OE mice. Unexpectedly, there were also group-related
      differences in chorda tympani nerve function, with OE mice showing a greater
      relative taste response to a concentration series of sucrose. Overall, our
      results show that disruption in peripheral innervation patterns of sensory
      neurons have significant effects on peripheral nerve function and central
      organization of their terminal fields. 

PMID- 25568133
TI  - Disturbed neuronal ER-Golgi sorting of unassembled glycine receptors suggests
      altered subcellular processing is a cause of human hyperekplexia.
AB  - Recent studies on the pathogenic mechanisms of recessive hyperekplexia indicate
      disturbances in glycine receptor (GlyR) alpha1 biogenesis. Here, we examine the
      properties of a range of novel glycine receptor mutants identified in human
      hyperekplexia patients using expression in transfected cell lines and primary
      neurons. All of the novel mutants localized in the large extracellular domain of
      the GlyR alpha1 have reduced cell surface expression with a high proportion of
      receptors being retained in the ER, although there is forward trafficking of
      glycosylated subpopulations into the ER-Golgi intermediate compartment and cis
      Golgi compartment. CD spectroscopy revealed that the mutant receptors have
      proportions of secondary structural elements similar to wild-type receptors. Two
      mutants in loop B (G160R, T162M) were functional, but none of those in loop
      D/beta2-3 were. One nonfunctional truncated mutant (R316X) could be rescued by
      coexpression with the lacking C-terminal domain. We conclude that a proportion of
      GlyR alpha1 mutants can be transported to the plasma membrane but do not
      necessarily form functional ion channels. We suggest that loop D/beta2-3 is an
      important determinant for GlyR trafficking and functionality, whereas alterations
      to loop B alter agonist potencies, indicating that residues here are critical
      elements in ligand binding. 

PMID- 25568135
TI  - Arterial stiffness: an independent determinant of adaptive glomerular
      hyperfiltration after kidney donation.
AB  - After kidney donation, the remaining kidney tends to hyperfiltrate, thus limiting
      the initial loss of renal function. The potential determinants of this adaptive
      glomerular hyperfiltration (GHF) and specifically the influence of arterial
      function are poorly known. In 45 normotensive healthy kidney donors [51 +/- 10 yr
      (mean +/- SD), 39 females], glomerular filtration rate (GFR) was measured as the
      clearance of continuously infused (99m)Tc-DTPA and timed urine collections at
      baseline, i.e., before donation, and 1 yr after donation. GHF was computed as
      postdonation GFR minus half of baseline GFR. Arterial function was assessed as
      baseline carotid-femoral pulse wave velocity (PWV) and carotid augmentation index
      (AIx). After kidney donation, no significant change in blood pressure (BP) was
      observed, but two subjects developed hypertension. GFR decreased from 107 +/- 19
      to 73 +/- 15 ml.min(-1).1.73 m(-2), and mean GHF was 20 +/- 10 ml.min(-1).1.73 m(
      2). In univariate analysis, GHF was inversely correlated to age (r(2) = 0.24, P =
      0.01), baseline PWV (r(2) = 0.23, P = 0.001), and Aix (r(2) = 0.11, P = 0.031).
      Nevertheless, GHF was not correlated to baseline peripheral or central BP. In
      multivariate analysis, baseline PWV, but not AIx, remained inversely correlated
      to GHF, independently of age, baseline mean BP, and GFR (model r(2) = 0.34, P <
      0.001). In healthy subjects selected for renal donation, increased arterial
      stiffness is associated with decreased postdonation compensatory hyperfiltration.

PMID- 25568134
TI  - Effect of dietary coarsely ground corn on broiler live performance,
      gastrointestinal tract development, apparent ileal digestibility of energy and
      nitrogen, and digesta particle size distribution and retention time.
AB  - Dietary structural material has been reported to improve broiler live performance
      and gastrointestinal tract (GIT) function. In this 50 d cage study, the effects
      of coarsely ground corn (CC) inclusion on broiler live performance, GIT
      development, apparent ileal digestibility (AID) of energy and nitrogen (N), and
      digesta particle size distribution and retention time were investigated. This
      study included 3 CC inclusions (0, 25, and 50% fine corn [FC] replaced by CC),
      with 6 replicate cages of 10 birds per treatment. The feed conversion ratio (FCR)
      at 35 and 42 d was improved (P<0.01) as the dietary inclusion of CC increased
      without effect on feed intake. The 50% CC diet increased absolute and relative
      gizzard weight at 42 d of age as compared to diets with 0 and 25% CC (P<0.01).
      Dietary CC increased absolute proventriculus weight at 28 d of age (P<0.05). A
      numerically lower gizzard digesta pH (P<0.08) was observed at 28 d but not 42 d
      of age, and there was no difference in proventriculus, jejunum, or ileum digesta
      pH at 28 or 42 d of age. The 25 and 50% CC treatments increased the digesta
      retention time at 30 and 45 d of age (P<0.05 and P<0.01, respectively). The 25
      and 50% CC treatments improved AID of energy by 7.1 and 8.2%, respectively, when
      compared with the 0% CC treatment, and they improved AID of N by 12.2 and 12.4%,
      respectively (P<0.01). The digesta particles in the jejunum exhibited a similar
      distribution, with a dgw (geometric mean diameter by mass) of 218, 204, and 181
      MUm when 0, 25, of 50% CC diets were consumed, respectively. In conclusion, birds
      fed pelleted and screened diets that contained 25 and 50% CC exhibited increased
      BW, improved FCR, and increased AID of energy and N, which was probably due to
      enhanced gizzard development and greater digesta retention time.

PMID- 25568138
TI  - Deficiency of BPOZ2 Decreases Liver Fibrosis After Chronic Carbon Tetrachloride
      Administration in Mice.
AB  - Bood POZ containing gene type 2 (BPOZ2), a Broad-Complex, Tramtrack, and Bric a
      brac domain containing protein, is an adaptor protein for the E3 ubiquitin ligase
      scaffold protein CUL3. It plays an important role in acute carbon tetrachloride
      (CCl4)-induced liver injury and regeneration in mice. In this study, we
      investigated the role of BPOZ2 in the process of liver fibrosis induced by
      chronic CCl4 treatment. The results indicate that BPOZ2 deficiency decreases
      sustained activation of hepatic stellate cells, attenuates collagen alphaI(I) and
      tissue inhibitor of matrix metalloprotease 1 expression, and decreases liver
      fibrosis after repeated CCl4 administration. These findings suggest BPOZ2 as a
      new therapeutic target for the prevention and treatment of hepatic fibrosis in
      chronic liver disease. 

PMID- 25568137
TI  - Tenofovir disoproxil fumarate: toxicity, toxicokinetics, and toxicogenomics
      analysis after 13 weeks of oral administration in mice.
AB  - Tenofovir disoproxil fumarate (TDF) is a prodrug of tenofovir that exhibits
      activity against HIV and hepatitis B. The goals of this study were to evaluate
      the molecular mechanism of TDF-induced toxicity in mice after 13 weeks of daily
      oral administration (50-1000 mg/kg) by correlating transcriptional changes with
      plasma drug levels and traditional toxicology end points. Plasma levels and
      systemic exposure of tenofovir increased less than dose proportionally and were
      similar on days 1 and 91. No overt toxicity was observed following the completion
      of TDF administration. The kidneys of TDF-treated mice were histopathologically
      normal. This result is consistent with the genomic microarray results, which
      showed no significant differences in kidney transcriptional levels between TDF
      treated animals and controls. In liver, after 4 and 13 weeks, cytomegaly was
      observed in mice treated with 1000 mg/kg of TDF, but mice recovered from this
      effect following cessation of administration. Analysis of liver transcripts on
      day 91 reported elevated levels of Cdkn1a in TDF-treated animals compared with
      controls, which may have contributed to the inhibition of liver cell cycle
      progression. 

PMID- 25568136
TI  - An angiotensin-(1-7) peptidase in the kidney cortex, proximal tubules, and human
      HK-2 epithelial cells that is distinct from insulin-degrading enzyme.
AB  - Angiotensin 1-7 [ANG-(1-7)] is expressed within the kidney and exhibits
      renoprotective actions that antagonize the inflammatory, fibrotic, and pro
      oxidant effects of ANG II. We previously identified an peptidase that
      preferentially metabolized ANG-(1-7) to ANG-(1-4) in the brain medulla and
      cerebrospinal fluid (CSF) of sheep (Marshall AC, Pirro NT, Rose JC, Diz DI,
      Chappell MC. J Neurochem 130: 313-323, 2014); thus the present study established
      the expression of the peptidase in the kidney. Utilizing a sensitive HPLC-based
      approach, we demonstrate a peptidase activity that hydrolyzed ANG-(1-7) to ANG-(1
      4) in the sheep cortex, isolated tubules, and human HK-2 renal epithelial cells.
      The peptidase was markedly sensitive to the metallopeptidase inhibitor JMV-390;
      human HK-2 cells expressed subnanomolar sensitivity (IC50 = 0.5 nM) and the
      highest specific activity (123 +/- 5 fmol.min(-1).mg(-1)) compared with the
      tubules (96 +/- 12 fmol.min(-1).mg(-1)) and cortex (107 +/- 9 fmol.min(-1).mg(
      1)). The peptidase was purified 41-fold from HK-2 cells; the activity was
      sensitive to JMV-390, the chelator o-phenanthroline, and the mercury-containing
      compound p-chloromercuribenzoic acid (PCMB), but not to selective inhibitors
      against neprilysin, neurolysin and thimet oligopeptidase. Both ANG-(1-7) and its
      endogenous analog [Ala(1)]-ANG-(1-7) (alamandine) were preferentially hydrolyzed
      by the peptidase compared with ANG II, [Asp(1)]-ANG II, ANG I, and ANG-(1-12).
      Although the ANG-(1-7) peptidase and insulin-degrading enzyme (IDE) share similar
      inhibitor characteristics of a metallothiolendopeptidase, we demonstrate marked
      differences in substrate specificity, which suggest these peptidases are
      distinct. We conclude that an ANG-(1-7) peptidase is expressed within the renal
      proximal tubule and may play a potential role in the renal renin-angiotensin
      system to regulate ANG-(1-7) tone.

PMID- 25568139
TI  - A national survey of troponin testing and recommendations for improved practice.
AB  - BACKGROUND: The introduction of troponin assays with higher analytical
      sensitivity and enhanced performance has produced new challenges for both
      laboratory and clinician in the optimal investigation of patients with
      cardiovascular disease. After some years of collective experience with this new
      generation of assays, this survey aimed to assess the level of consensus that
      exists regarding their application. METHODS: A questionnaire was designed, based
      on a review of published evidence and current opinion, to obtain information on a
      number of key areas relating to troponin analysis and reporting and was
      circulated to lead laboratory consultants across the UK and Ireland. RESULTS:
      Completed questionnaires were received from 94 laboratory contacts. Sixty per
      cent of those who responded had implemented a high-sensitivity troponin assay,
      with the Roche Cobas troponin T high sensitivity assay the most widely used. It
      is evident that some confusion remains regarding the definition of high
      sensitivity assays and there was considerable variation in practice, even among
      those using the same manufacturer's assay. CONCLUSIONS: There is a need for
      greater consensus in the approach to the clinical utilization of troponin assays
      with improved sensitivity and it is important that laboratories are fully aware
      of the capabilities of their assay and provide useful guidance to users. On the
      basis of survey findings and the existing evidence base, a number of
      recommendations have been proposed to improve current practice and enhance
      patient safety.

PMID- 25568140
TI  - Serum albumin-adjusted glycated albumin is a better indicator of glycaemic
      control in diabetic patients with end-stage renal disease not on haemodialysis.
AB  - BACKGROUNDS: Diabetic patients with end-stage renal disease who are not on
      haemodialysis show low concentrations of HbA1c and glycated albumin due to renal
      anaemia and proteinuria, respectively. In the present study, we examined whether
      serum albumin-adjusted glycated albumin could accurately reflect glycaemic
      control in these patients. METHODS: To examine the correlation between glycated
      albumin and serum albumin (Study 1), 49 diabetic patients with end-stage renal
      disease not on haemodialysis were used. To evaluate the association between the
      glycaemic control indicators and the glycaemic control state (Study 2), 30
      diabetic patients with end-stage renal disease were enrolled. The estimated HbA1c
      and the estimated glycated albumin concentrations were calculated based on the
      mean blood glucose concentrations obtained from the diurnal variation. The
      adjusted glycated albumin concentrations were calculated from the regression
      formula between the serum albumin and glycated albumin obtained from Study 1.
      RESULTS: No significant correlation was found between the measured HbA1c and
      estimated HbA1c concentrations. The estimated HbA1c (inversely) and measured
      HbA1c/estimated HbA1c ratio (positively), but not measured HbA1c, showed a
      significant correlation with Hb concentrations. The estimated glycated albumin
      was positively associated with the measured glycated albumin and adjusted
      glycated albumin concentrations. Although measured glycated albumin/estimated
      glycated albumin ratio was positively correlated with serum albumin, there was no
      significant association between the adjusted glycated albumin/estimated glycated
      albumin ratio and serum albumin, Hb and estimated glomerular filtration rate.
      CONCLUSIONS: We found for the first time that the adjustment of glycated albumin
      by serum albumin could be useful to determine glycaemic control in diabetic
      patients with end-stage renal disease not on haemodialysis. These findings
      suggest that adjusted glycated albumin might be a better indicator of glycaemic
      control than measured HbA1c and measured glycated albumin in these patients.

PMID- 25568141
TI  - Real-time information on preventable death provided by email from frontline
      intensivists: results in high response rates with useful information.

PMID- 25568142
TI  - Development of a real-time repeated-measures assessment protocol to capture
      change over the course of a drinking episode.
AB  - AIMS: We report on the development of a real-time assessment protocol that allows
      researchers to assess change in BrAC, alcohol responses, behaviors, and contexts
      over the course of a drinking event. METHOD: We designed a web application that
      uses timed text messages (adjusted based on consumption pattern) containing links
      to our website to obtain real-time participant reports; camera and location
      features were also incorporated into the protocol. We used a transdermal alcohol
      sensor device along with software we designed to convert transdermal data into
      estimated BrAC. Thirty-two college students completed a laboratory session
      followed by a 2-week field trial. RESULTS: Results for the web application
      indicated we were able to create an effective tool for obtaining repeated
      measures real-time drinking data. Participants were willing to monitor their
      drinking behavior with the web application, and this did not appear to strongly
      affect drinking behavior during, or 6 weeks following, the field trial. Results
      for the transdermal device highlighted the willingness of participants to wear
      the device despite some discomfort, but technical difficulties resulted in
      limited valid data. CONCLUSION: The development of this protocol makes it
      possible to capture detailed assessment of change over the course of naturalistic
      drinking episodes.

PMID- 25568143
TI  - The impact of measurement frequency on the domains of glycemic control in the
      critically ill--a Monte Carlo simulation.
AB  - The role of blood glucose (BG) measurement frequency on the domains of glycemic
      control is not well defined. This Monte Carlo mathematical simulation of glycemic
      control in a cohort of critically ill patients modeled sets of 100 patients with
      simulated BG-measuring devices having 5 levels of measurement imprecision, using
      2 published insulin infusion protocols, for 200 hours, with 3 different BG
      measurement intervals-15 minutes (Q15'), 1 hour (Q1h), and 2 hours (Q2h)
      resulting in 1,100,000 BG measurements for 3000 simulated patients. The model
      varied insulin sensitivity, initial BG value and rate of gluconeogenesis. The
      primary outcomes included rates of hyperglycemia (BG > 180 mg/dL), hypoglycemia
      (BG < 70 and 40 mg/dL), proportion of patients with elevated glucose variability
      (within-patient coefficient of variation [CV] > 20%), and time in range (BG
      ranges 80-150 mg/dL and 80-180 mg/dL). Percentages of hyperglycemia, hypoglycemia
      at both thresholds, and patients with elevated glucose variability as well as
      time outside glycemic targets were substantially higher in simulations with
      measurement interval Q2h compared to those with measurement interval Q1h and
      moderately higher in simulations with Q1h than in those with Q15'. Higher
      measurement frequency mitigated the deleterious effect of high measurement
      imprecision, defined as CV >= 15%. This Monte Carlo simulation suggests that
      glycemic control in critically ill patients is more optimal with a BG measurement
      interval no longer than 1h, with further benefit obtained with use of measurement
      interval of 15'. These findings have important implications for the development
      of glycemic control standards.

PMID- 25568144
TI  - Physical activity and type 1 diabetes: time for a rewire?
AB  - While being physically active bestows many health benefits on individuals with
      type 1 diabetes, their overall blood glucose control is not enhanced without an
      effective balance of insulin dosing and food intake to maintain euglycemia
      before, during, and after exercise of all types. At present, a number of
      technological advances are already available to insulin users who desire to be
      physically active with optimal blood glucose control, although a number of
      limitations to those devices remain. In addition to continued improvements to
      existing technologies and introduction of new ones, finding ways to integrate all
      of the available data to optimize blood glucose control and performance during
      and following exercise will likely involve development of "smart" calculators,
      enhanced closed-loop systems that are able to use additional inputs and learn,
      and social aspects that allow devices to meet the needs of the users. 

PMID- 25568145
TI  - Cytomegalovirus in pediatric systemic lupus erythematosus: prevalence and
      clinical manifestations.
AB  - Cytomegalovirus (CMV) is a beta-herpesvirus and antibodies to this virus are
      common in patients with systemic lupus erythematosus (SLE). However, few studies
      have examined the relationship between CMV infection and SLE. OBJECTIVES: Our
      objectives were: 1) to determine the prevalence of CMV infection at the time of
      SLE diagnosis, and 2) to determine the risk factors for CMV infection. METHODS: A
      database review of 670 patients with pediatric SLE (pSLE) seen over a 20-year
      period identified seven patients with a CMV infection detected at the time of
      diagnosis of SLE. CMV was diagnosed by serology, urine and bronchoalveolar
      lavage. Clinical manifestations, laboratory findings, virology studies and
      treatments were reviewed. RESULTS: CMV infection was detected in seven patients
      at the time of SLE diagnosis (1.04% of total cohort): six were female: mean age
      was 13 years. Predominant features included non-Caucasian ethnicity (p < 0.01 as
      compared to total SLE cohort), persistent fevers on prednisone in seven and
      nephrotic syndrome in four. Laboratory findings included: anemia in seven,
      lymphopenia in five, elevated liver enzymes in four, with anti-dsDNA and anti-RNP
      antibodies present in six and five, respectively. Six patients received
      ganciclovir and CMV hyperimmune globulin (Cytogam(r)) with the continuation of
      prednisone during CMV treatment. Six of seven fully recovered without sequelae
      (one without treatment) but one patient died with active CMV infection.
      CONCLUSIONS: There were 1.04% of patients with pSLE who developed CMV infection.
      All were of non-Caucasian ethnicity. Persistent fever despite prednisone, with
      concomitant anemia, may be additional clues to CMV infection in pSLE. We suggest
      all patients have routine testing for CMV immunity at initial presentation of
      pSLE.

PMID- 25568147
TI  - Alectinib induces a durable (>15 months) complete response in an ALK-positive non
      small cell lung cancer patient who progressed on crizotinib with diffuse
      leptomeningeal carcinomatosis.

PMID- 25568146
TI  - Identifying and addressing the needs of adolescents and young adults with cancer:
      summary of an Institute of Medicine workshop.
AB  - Cancer is the leading disease-related cause of death in adolescents and young
      adults (AYAs). This population faces many short- and long-term health and
      psychosocial consequences of cancer diagnosis and treatment, but many programs
      for cancer treatment, survivorship care, and psychosocial support do not focus on
      the specific needs of AYA cancer patients. Recognizing this health care
      disparity, the National Cancer Policy Forum of the Institute of Medicine convened
      a public workshop to examine the needs of AYA patients with cancer. Workshop
      participants identified many gaps and challenges in the care of AYA cancer
      patients and discussed potential strategies to address these needs. Suggestions
      included ways to improve access to care for AYAs, to deliver cancer care that
      better meets the medical and psychosocial needs of AYAs, to develop educational
      programs for providers who care for AYA cancer survivors, and to enhance the
      evidence base for AYAs with cancer by facilitating participation in research. 

PMID- 25568148
TI  - Practical management of bevacizumab-related toxicities in glioblastoma.
AB  - Bevacizumab, currently an option for treatment of different types of tumors
      including glioblastoma, has a peculiar toxicity profile related to its
      antiangiogenic effect. Because some bevacizumab-related adverse events can be
      life threatening, it is important to identify risk factors and to establish
      treatment protocols to minimize treatment-related morbidity and mortality. In
      glioblastoma patients, the risk of developing certain side effects, such as
      gastrointestinal perforation, venous thromboembolism, and intracranial
      hemorrhages, is slightly higher than in patients treated with bevacizumab for
      other tumor types. We performed a systematic review of the side effects of
      bevacizumab and their incidence, causal mechanisms, and available treatments.
      Finally, we identified risk factors and proposed preventive and therapeutic
      measures for these adverse events. 

PMID- 25568149
TI  - Interhemispheric Asymmetries and Theta Activity in the Rostral Anterior Cingulate
      Cortex as EEG Signature of HIV-Related Depression: Gender Matters.
AB  - Resting EEGs of 40 people living with HIV (PLWH) on long-term antiretroviral
      treatment were examined for z-scored deviations from a healthy control (normative
      database) to examine the main and interaction effects of depression and gender.
      Regions of interest were frontal (alpha) and central (all bands) for
      interhemispheric asymmetries in quantitative EEGs and theta in the rostral
      anterior cingulate cortex (rACC) in low-resolution electromagnetic tomography
      (LORETA). Z-scored normed deviations of depressed PLWH, compared with
      nondepressed, showed right-dominant interhemispheric asymmetries in all regions.
      However, after adjusting for multiple testing, significance remained only central
      for theta, alpha, and beta. Reversed (left-dominant) frontal alpha asymmetry is a
      potential EEG marker of depression in the HIV negative population that was not
      reversed in depressive PLWH; however, corresponding with extant literature,
      gender had an effect on the size of frontal alpha asymmetry. The LORETA analysis
      revealed a trending interactional effect of depression and gender on theta
      activity in the rACC in Brodmann area 32. We found that compared to men, women
      had greater right-dominant frontal alpha-asymmetry and elevated theta activity in
      voxels of the rACC, which may indicate less likelihood of depression and a higher
      likelihood of response to antidepressants. In conclusion, subtle EEG deviations,
      such as right-dominant central theta, alpha, and beta asymmetries and theta
      activity in the rACC may mark HIV-related depressive symptoms and may predict the
      likelihood of response to antidepressants but gender effects need to be taken
      into account. Although this study introduced the use of LORETA to examine the
      neurophysiological correlates of negative affect in PLWH, further research is
      needed to assess the utility of this tool in diagnostics and treatment monitoring
      of depression in PLWH. 

PMID- 25568150
TI  - WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome.
AB  - Autophagy is a pivotal cytoprotective process that secures cellular homeostasis,
      fulfills essential roles in development, immunity and defence against pathogens,
      and determines the lifespan of eukaryotic organisms. However, autophagy also
      crucially contributes to the development of age-related human pathologies,
      including cancer and neurodegeneration. Macroautophagy (hereafter referred to as
      autophagy) clears the cytoplasm by stochastic or specific cargo recognition and
      destruction, and is initiated and executed by autophagy related (ATG) proteins
      functioning in dynamical hierarchies to form autophagosomes. Autophagosomes
      sequester cytoplasmic cargo material, including proteins, lipids and organelles,
      and acquire acidic hydrolases from the lysosomal compartment for cargo
      degradation. Prerequisite and essential for autophagosome formation is the
      production of phosphatidylinositol 3-phosphate (PtdIns3P) by phosphatidylinositol
      3-kinase class III (PI3KC3, also known as PIK3C3) in complex with beclin 1, p150
      (also known as PIK3R4; Vps15 in yeast) and ATG14L. Members of the human WD-repeat
      protein interacting with phosphoinositides (WIPI) family play an important role
      in recognizing and decoding the PtdIns3P signal at the nascent autophagosome, and
      hence function as autophagy-specific PtdIns3P-binding effectors, similar to their
      ancestral yeast Atg18 homolog. The PtdIns3P effector function of human WIPI
      proteins appears to be compromised in cancer and neurodegeneration, and WIPI
      genes and proteins might present novel targets for rational therapies. Here, we
      summarize the current knowledge on the roles of the four human WIPI proteins,
      WIPI1-4, in autophagy. This article is part of a Focus on Autophagosome
      biogenesis. For further reading, please see related articles: 'ERES: sites for
      autophagosome biogenesis and maturation?' by Jana Sanchez-Wandelmer et al. (J.
      Cell Sci. 128, 185-192) and 'Membrane dynamics in autophagosome biogenesis' by
      Sven R. Carlsson and Anne Simonsen (J. Cell Sci. 128, 193-205). 

PMID- 25568151
TI  - Membrane dynamics in autophagosome biogenesis.
AB  - Bilayered phospholipid membranes are vital to the organization of the living
      cell. Based on fundamental principles of polarity, membranes create borders
      allowing defined spaces to be encapsulated. This compartmentalization is a
      prerequisite for the complex functional design of the eukaryotic cell, yielding
      localities that can differ in composition and operation. During macroautophagy,
      cytoplasmic components become enclosed by a growing double bilayered membrane,
      which upon closure creates a separate compartment, the autophagosome. The
      autophagosome is then primed for fusion with endosomal and lysosomal
      compartments, leading to degradation of the captured material. A large number of
      proteins have been found to be essential for autophagy, but little is known about
      the specific lipids that constitute the autophagic membranes and the membrane
      modeling events that are responsible for regulation of autophagosome shape and
      size. In this Commentary, we review the recent progress in our understanding of
      the membrane shaping and remodeling events that are required at different steps
      of the autophagy pathway. This article is part of a Focus on Autophagosome
      biogenesis. For further reading, please see related articles: 'ERES: sites for
      autophagosome biogenesis and maturation?' by Jana Sanchez-Wandelmer et al. (J.
      Cell Sci. 128, 185-192) and 'WIPI proteins: essential PtdIns3P effectors at the
      nascent autophagosome' by Tassula Proikas-Cezanne et al. (J. Cell Sci. 128, 207
      217). 

PMID- 25568152
TI  - ERES: sites for autophagosome biogenesis and maturation?
AB  - Autophagosomes are the hallmark of autophagy, but despite their central role in
      this degradative pathway that involves vesicle transport to lysosomes or
      vacuoles, the mechanism underlying their biogenesis still remains largely
      unknown. Our current concepts about autophagosome biogenesis are based on models
      suggesting that a small autonomous cisterna grows into an autophagosome through
      expansion at its extremities. Recent findings have revealed that endoplasmic
      reticulum (ER) exit sites (ERES), specialized ER regions where proteins are
      sorted into the secretory system, are key players in the formation of
      autophagosomes. Owing to the morphological connection of nascent autophagosomes
      with the ER, this has raised several questions that challenge our current
      perception of autophagosome biogenesis, such as are ERES the compartments where
      autophagosome formation takes place? What is the functional relevance of this
      connection? Are these compartments providing essential molecules for the
      generation of autophagosomes and/or are they structural platforms where these
      vesicles emerge? In this Hypothesis, we discuss recent data that have implicated
      the ERES in autophagosome biogenesis and we propose two models to describe the
      possible role of this compartment at different steps in the process of
      autophagosome biogenesis. This article is part of a Focus on Autophagosome
      biogenesis. For further reading, please see related articles: 'Membrane dynamics
      in autophagosome biogenesis' by Sven R. Carlsson and Anne Simonsen (J. Cell Sci.
      128, 193-205) and 'WIPI proteins: essential PtdIns3P effectors at the nascent
      autophagosome' by Tassula Proikas-Cezanne et al. (J. Cell Sci. 128, 207-217).

PMID- 25568153
TI  - Mutation accumulation and the formation of range limits.
AB  - The dynamics of range formation are important for understanding and predicting
      species distributions. Here, we focus on a process that has thus far been
      overlooked in the context of range formation; the accumulation of mutation load.
      We find that mutation accumulation severely reduces the extent of a range across
      an environmental gradient, especially when dispersal is limited, growth rate is
      low and mutations are of intermediate deleterious effect. Our results illustrate
      the important role deleterious mutations can play in range formation. We
      highlight this as a necessary focus for further work, noting particularly the
      potentially conflicting effects dispersal may have in reducing mutation load and
      simultaneously increasing migration load in marginal populations. 

PMID- 25568154
TI  - Lungs of the first amniotes: why simple if they can be complex?
AB  - We show-in contrast to the traditional textbook contention-that the first amniote
      lungs were complex, multichambered organs and that the single-chambered lungs of
      lizards and snakes represent a secondarily simplified rather than the
      plesiomorphic condition. We combine comparative anatomical and embryological data
      and show that shared structural principles of multichamberedness are recognizable
      in amniotes including all lepidosaurian taxa. Sequential intrapulmonary branching
      observed during early organogenesis becomes obscured during subsequent growth,
      resulting in a secondarily simplified, functionally single-chambered lung in
      lepidosaurian adults. Simplification of pulmonary structure maximized the size of
      the smallest air spaces and eliminated biophysically compelling surface tension
      problems that were associated with miniaturization evident among stem
      lepidosaurmorphs. The remaining amniotes, however, retained the multichambered
      lungs, which allowed both large surface area and high pulmonary compliance, thus
      initially providing a strong selective advantage for efficient respiration in
      terrestrial environments. Branched, multichambered lungs instead of simple, sac
      like organs were part and parcel of the respiratory apparatus of the first
      amniotes and pivotal for their success on dry land, with the sky literally as the
      limit. 

PMID- 25568155
TI  - A Middle Triassic thoracopterid from China highlights the evolutionary origin of
      overwater gliding in early ray-finned fishes.
AB  - Gliding adaptations in thoracopterid flying fishes represent a remarkable case of
      convergent evolution of overwater gliding strategy with modern exocoetid flying
      fishes, but the evolutionary origin of this strategy was poorly known in the
      thoracopterids because of lack of transitional forms. Until recently, all
      thoracopterids, from the Late Triassic of Austria and Italy and the Middle
      Triassic of South China, were highly specialized 'four-winged' gliders in having
      wing-like paired fins and an asymmetrical caudal fin with the lower caudal lobe
      notably larger than the upper lobe. Here, we show that the new genus Wushaichthys
      and the previously alleged 'peltopleurid' Peripeltopleurus, from the Middle
      Triassic (Ladinian, 235-242 Ma) of South China and near the Ladinian/Anisian
      boundary of southern Switzerland and northern Italy, respectively, represent the
      most primitive and oldest known thoracopterids. Wushaichthys, the most basal
      thoracopterid, shows certain derived features of this group in the skull.
      Peripeltopleurus shows a condition intermediate between Wushaichthys and
      Thoracopterus in having a slightly asymmetrical caudal fin but still lacking wing
      like paired fins. Phylogenetic studies suggest that the evolution of overwater
      gliding of thoracopterids was gradual in nature; a four-stage adaption following
      the 'cranial specialization-asymmetrical caudal fin-enlarged paired fins-scale
      reduction' sequence has been recognized in thoracopterid evolution. Moreover,
      Wushaichthys and Peripeltopleurus bear hooklets on the anal fin of supposed
      males, resembling those of modern viviparious teleosts. Early thoracopterids
      probably had evolved a live-bearing reproductive strategy. 

PMID- 25568156
TI  - Role of Na+/Ca2+ exchanger in Ca2+ homeostasis in rat suprachiasmatic nucleus
      neurons.
AB  - Intracellular Ca(2+) is critical to the central clock of the suprachiasmatic
      nucleus (SCN). However, the role of Na(+)/Ca(2+) exchanger (NCX) in intracellular
      Ca(2+) concentration ([Ca(2+)]i) homeostasis in the SCN is unknown. Here we show
      that NCX is an important mechanism for somatic Ca(2+) clearance in SCN neurons.
      In control conditions Na(+)-free solution lowered [Ca(2+)]i by inhibiting TTX
      sensitive as well as nimodipine-sensitive Ca(2+) influx. With use of the Na(+)
      ionophore monensin to raise intracellular Na(+) concentration ([Na(+)]i), Na(+)
      free solution provoked rapid Ca(2+) uptake via reverse NCX. The peak amplitude of
      0 Na(+)-induced [Ca(2+)]i increase was larger during the day than at night, with
      no difference between dorsal and ventral SCN neurons. Ca(2+) extrusion via
      forward NCX was studied by determining the effect of Na(+) removal on Ca(2+)
      clearance after high-K(+)-induced Ca(2+) loads. The clearance of Ca(2+) proceeded
      with two exponential decay phases, with the fast decay having total signal
      amplitude of ~85% and a time constant of ~7 s. Na(+)-free solution slowed the
      fast decay rate threefold, whereas mitochondrial protonophore prolonged mostly
      the slow decay. In contrast, blockade of plasmalemmal and sarco(endo)plasmic
      reticulum Ca(2+) pumps had little effect on the kinetics of Ca(2+) clearance. RT
      PCR indicated the expression of NCX1 and NCX2 mRNAs. Immunohistochemical staining
      showed the presence of NCX1 immunoreactivity in the whole SCN but restricted
      distribution of NCX2 immunoreactivity in the ventrolateral SCN. Together our
      results demonstrate an important role of NCX, most likely NCX1, as well as
      mitochondrial Ca(2+) uptake in clearing somatic Ca(2+) after depolarization
      induced Ca(2+) influx in SCN neurons.

PMID- 25568157
TI  - Different types of retinal inhibition have distinct neurotransmitter release
      properties.
AB  - Neurotransmitter release varies between neurons due to differences in presynaptic
      mechanisms such as Ca(2+) sensitivity and timing. Retinal rod bipolar cells
      respond to brief dim illumination with prolonged glutamate release that is tuned
      by the differential release of GABA and glycine from amacrine cells in the inner
      retina. To test if differences among types of GABA and glycine release are due to
      inherent amacrine cell release properties, we directly activated amacrine cell
      neurotransmitter release by electrical stimulation. We found that the timing of
      electrically evoked inhibitory currents was inherently slow and that the
      timecourse of inhibition from slowest to fastest was GABAC receptors > glycine
      receptors > GABAA receptors. Deconvolution analysis showed that the distinct
      timing was due to differences in prolonged GABA and glycine release from amacrine
      cells. The timecourses of slow glycine release and GABA release onto GABAC
      receptors were reduced by Ca(2+) buffering with EGTA-AM and BAPTA-AM, but faster
      GABA release on GABAA receptors was not, suggesting that release onto GABAA
      receptors is tightly coupled to Ca(2+). The differential timing of GABA release
      was detected from spiking amacrine cells and not nonspiking A17 amacrine cells
      that form a reciprocal synapse with rod bipolar cells. Our results indicate that
      release from amacrine cells is inherently asynchronous and that the source of
      nonreciprocal rod bipolar cell inhibition differs between GABA receptors. The
      slow, differential timecourse of inhibition may be a mechanism to match the
      prolonged rod bipolar cell glutamate release and provide a way to temporally tune
      information across retinal pathways. 

PMID- 25568158
TI  - The eye in hand: predicting others' behavior by integrating multiple sources of
      information.
AB  - The ability to predict the outcome of other beings' actions confers significant
      adaptive advantages. Experiments have assessed that human action observation can
      use multiple information sources, but it is currently unknown how they are
      integrated and how conflicts between them are resolved. To address this issue, we
      designed an action observation paradigm requiring the integration of multiple,
      potentially conflicting sources of evidence about the action target: the actor's
      gaze direction, hand preshape, and arm trajectory, and their availability and
      relative uncertainty in time. In two experiments, we analyzed participants'
      action prediction ability by using eye tracking and behavioral measures. The
      results show that the information provided by the actor's gaze affected
      participants' explicit predictions. However, results also show that gaze
      information was disregarded as soon as information on the actor's hand preshape
      was available, and this latter information source had widespread effects on
      participants' prediction ability. Furthermore, as the action unfolded in time,
      participants relied increasingly more on the arm movement source, showing
      sensitivity to its increasing informativeness. Therefore, the results suggest
      that the brain forms a robust estimate of the actor's motor intention by
      integrating multiple sources of information. However, when informative motor cues
      such as a preshaped hand with a given grip are available and might help in
      selecting action targets, people tend to capitalize on such motor cues, thus
      turning out to be more accurate and fast in inferring the object to be
      manipulated by the other's hand. 

PMID- 25568160
TI  - Early and late beta-band power reflect audiovisual perception in the McGurk
      illusion.
AB  - The McGurk illusion is a prominent example of audiovisual speech perception and
      the influence that visual stimuli can have on auditory perception. In this
      illusion, a visual speech stimulus influences the perception of an incongruent
      auditory stimulus, resulting in a fused novel percept. In this high-density
      electroencephalography (EEG) study, we were interested in the neural signatures
      of the subjective percept of the McGurk illusion as a phenomenon of speech
      specific multisensory integration. Therefore, we examined the role of cortical
      oscillations and event-related responses in the perception of congruent and
      incongruent audiovisual speech. We compared the cortical activity elicited by
      objectively congruent syllables with incongruent audiovisual stimuli.
      Importantly, the latter elicited a subjectively congruent percept: the McGurk
      illusion. We found that early event-related responses (N1) to audiovisual stimuli
      were reduced during the perception of the McGurk illusion compared with congruent
      stimuli. Most interestingly, our study showed a stronger poststimulus suppression
      of beta-band power (13-30 Hz) at short (0-500 ms) and long (500-800 ms) latencies
      during the perception of the McGurk illusion compared with congruent stimuli. Our
      study demonstrates that auditory perception is influenced by visual context and
      that the subsequent formation of a McGurk illusion requires stronger audiovisual
      integration even at early processing stages. Our results provide evidence that
      beta-band suppression at early stages reflects stronger stimulus processing in
      the McGurk illusion. Moreover, stronger late beta-band suppression in McGurk
      illusion indicates the resolution of incongruent physical audiovisual input and
      the formation of a coherent, illusory multisensory percept.

PMID- 25568159
TI  - Electrophysiological properties of genetically identified subtypes of layer 5
      neocortical pyramidal neurons: Ca2+ dependence and differential modulation by
      norepinephrine.
AB  - We studied neocortical pyramidal neurons from two lines of bacterial artificial
      chromosome mice (etv1 and glt; Gene Expression Nervous System Atlas: GENSAT
      project), each of which expresses enhanced green fluorescent protein (EGFP) in a
      different subpopulation of layer 5 pyramidal neurons. In barrel cortex, etv1 and
      glt pyramidal cells were previously reported to differ in terms of their laminar
      distribution, morphology, thalamic inputs, cellular targets, and receptive field
      size. In this study, we measured the laminar distribution of etv1 and glt cells.
      On average, glt cells were located more deeply; however, the distributions of
      etv1 and glt cells extensively overlap in layer 5. To test whether these two cell
      types differed in electrophysiological properties that influence firing behavior,
      we prepared acute brain slices from 2-4-wk-old mice, where EGFP-positive cells in
      somatosensory cortex were identified under epifluorescence and then studied using
      whole cell current- or voltage-clamp recordings. We studied the details of action
      potential parameters and repetitive firing, characterized by the larger slow
      afterhyperpolarizations (AHPs) in etv1 neurons and larger medium AHPs (mAHPS) in
      glt cells, and compared currents underlying the mAHP and slow AHP (sAHP) in etv1
      and glt neurons. Etv1 cells exhibited lower dV/dt for spike polarization and
      repolarization and reduced direct current (DC) gain (lower f-I slope) for
      repetitive firing than glt cells. Most importantly, we found that 1) differences
      in the expression of Ca(2+)-dependent K(+) conductances (small-conductance
      calcium-activated potassium channels and sAHP channels) determine major
      functional differences between etv1 and glt cells, and 2) there is differential
      modulation of etv1 and glt neurons by norepinephrine. 

PMID- 25568161
TI  - A common stochastic accumulator with effector-dependent noise can explain eye
      hand coordination.
AB  - The computational architecture that enables the flexible coupling between
      otherwise independent eye and hand effector systems is not understood. By using a
      drift diffusion framework, in which variability of the reaction time (RT)
      distribution scales with mean RT, we tested the ability of a common stochastic
      accumulator to explain eye-hand coordination. Using a combination of behavior,
      computational modeling and electromyography, we show how a single stochastic
      accumulator to threshold, followed by noisy effector-dependent delays, explains
      eye-hand RT distributions and their correlation, while an alternate independent,
      interactive eye and hand accumulator model does not. Interestingly, the common
      accumulator model did not explain the RT distributions of the same subjects when
      they made eye and hand movements in isolation. Taken together, these data suggest
      that a dedicated circuit underlies coordinated eye-hand planning. 

PMID- 25568163
TI  - Lack of glucagon receptor signaling and its implications beyond glucose
      homeostasis.
AB  - Glucagon action is transduced by a G protein-coupled receptor located in liver,
      kidney, intestinal smooth muscle, brain, adipose tissue, heart, pancreatic beta
      cells, and placenta. Genetically modified animal models have provided important
      clues about the role of glucagon and its receptor (Gcgr) beyond glucose control.
      The PubMed database was searched for articles published between 1995 and 2014
      using the key terms glucagon, glucagon receptor, signaling, and animal models.
      Lack of Gcgr signaling has been associated with: i) hypoglycemic pregnancies,
      altered placentation, poor fetal growth, and increased fetal-neonatal death; ii)
      pancreatic glucagon cell hyperplasia and hyperglucagonemia; iii) altered body
      composition, energy state, and protection from diet-induced obesity; iv) impaired
      hepatocyte survival; v) altered glucose, lipid, and hormonal milieu; vi) altered
      metabolic response to prolonged fasting and exercise; vii) reduced gastric
      emptying and increased intestinal length; viii) altered retinal function; and ix)
      prevention of the development of diabetes in insulin-deficient mice. Similar
      phenotypic findings were observed in the hepatocyte-specific deletion of Gcgr.
      Glucagon action has been involved in the modulation of sweet taste
      responsiveness, inotropic and chronotropic effects in the heart, satiety,
      glomerular filtration rate, secretion of insulin, cortisol, ghrelin, GH,
      glucagon, and somatostatin, and hypothalamic signaling to suppress hepatic
      glucose production. Glucagon (alpha) cells under certain conditions can
      transdifferentiate into insulin (beta) cells. These findings suggest that
      glucagon signaling plays an important role in multiple organs. Thus, treatment
      options designed to block Gcgr activation in diabetics may have implications
      beyond glucose homeostasis. 

PMID- 25568162
TI  - Visual experience prevents dysregulation of GABAB receptor-dependent short-term
      depression in adult superior colliculus.
AB  - Progressive loss of plasticity during development prevents refined circuits from
      regressing to an immature state and is thought to depend on maturation of
      GABAergic inhibition. For example, a gradual reduction in size of visual
      receptive fields (RFs) occurs in the superior colliculus (SC) during development.
      Maintenance of the refined state throughout adulthood requires early light
      exposure. Here we investigate the potential role of changes in long- or short
      term plasticity in experience-dependent maintenance of refined RFs. Using an
      acute SC slice preparation, we found that long-term plasticity was not affected
      by visual deprivation, indicating that it does not underlie deprivation-induced
      RF enlargement. In contrast, visual deprivation altered short-term plasticity in
      an unexpected way. Specifically, GABAB receptor (GABABR)-mediated paired pulse
      depression was increased in slices from dark-reared animals. This increase was
      mimicked by GABAAR blockade in slices from normally reared animals, suggesting
      that experience-dependent maintenance of GABAAR function prevents an increase in
      probability of neurotransmitter release. GABABR-mediated short-term depression in
      response to strong stimulation (such as occurs during vision) was reduced in
      slices from dark-reared animals. This change was mimicked in slices from normal
      animals by reducing GABA release. These results are consistent with the
      hypothesis that early visual experience maintains GABAergic inhibition and
      prevents later deprivation-induced alterations of short-term depression in SC.
      Identifying how plasticity is restricted in mature circuits could guide therapies
      to enhance recovery of function in adults. 

PMID- 25568164
TI  - Safety assessment of Tin(IV) oxide as used in cosmetics.
AB  - Tin(IV) oxide functions as an abrasive, bulking, and opacifying agent in cosmetic
      products and is used at concentrations up to 0.4% in rinse-off products and up to
      1.3% in leave-on products. The Cosmetic Ingredient Review Expert Panel (Panel)
      noted that tin(IV) oxide is a water-insoluble inorganic metal compound and should
      not be percutaneously absorbed; therefore, systemic exposure is not likely.
      Studies of dermal application of tin(IV) oxide were considered to determine
      toxicity at the site of application. The Panel concluded that tin(IV) oxide is
      safe in the present practices of use and concentration. 

PMID- 25568165
TI  - Safety assessment of nylon as used in cosmetics.
AB  - The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of nylon
      polymers, which function in cosmetics primarily as bulking and opacifying agents.
      The Panel reviewed relevant animal and human data related to these large polymers
      and determined that they are not likely to penetrate the skin. Whatever residual
      monomers may be present were not present at a sufficient level to cause any
      reactions in test subjects at the maximum ingredient use concentration.
      Accordingly, the Panel concluded that these ingredients are safe in the present
      practices of use and concentration. 

PMID- 25568166
TI  - Validation of family cancer history data in high-risk families: the influence of
      cancer site, ethnicity, kinship degree, and multiple family reporters.
AB  - Information on family cancer history (FCH) is often collected for first-degree
      relatives, but more extensive FCH information is critical for greater accuracy in
      risk assessment. Using self-reported diagnosis of cancer as the gold standard, we
      examined differences in the sensitivity and specificity of relative-reported FCH
      by cancer site, race/ethnicity, language preference, and kinship degree (1,524
      individuals from 557 families; average number of relatives per family = 2.7). We
      evaluated the impact of FCH data collected in 2007-2013 from multiple relatives
      by comparing mean values and proportions for the number of relatives with any
      cancer, breast cancer, or ovarian cancer as reported by a single relative and by
      multiple relatives in the same family. The sensitivity of FCH was lower in
      Hispanics, Spanish-speaking persons, and third-degree relatives (e.g., for all
      cancers, sensitivities were 80.7%, 87.4%, and 91.0% for third-, second-, and
      first-degree relatives, respectively). FCH reported by multiple relatives
      included a higher number of relatives with cancer than the number reported by a
      single relative (e.g., mean increase of 1.2 relatives with any cancer), with more
      relatives diagnosed with any cancer, breast cancer, and ovarian cancer in 52%,
      36% and 12% of families, respectively. Collection of FCH data from multiple
      relatives may provide a more comprehensive picture of FCH and may potentially
      improve risk assessment and preventive care. 

PMID- 25568168
TI  - Health and politics for 2015 and beyond.

PMID- 25568167
TI  - Informed cytology for triaging HPV-positive women: substudy nested in the NTCC
      randomized controlled trial.
AB  - BACKGROUND: Human papillomavirus (HPV)-based screening needs triage. In most
      randomized controlled trials (RCTs) on HPV testing with cytological triage,
      cytology interpretation has been blind to HPV status. METHODS: Women age 25 to 60
      years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV
      testing with cytology were referred to colposcopy if HPV positive and, if no
      cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV
      negativity. Cytological slides taken at the first colposcopy were retrieved and
      independently interpreted by an external laboratory, which was only aware of
      patients' HPV positivity. Sensitivity, specificity, and positive (PPV) and
      negative (NPV) predictive values were computed for histologically proven CIN2+
      with HPV status-informed cytology for women with a determination of atypical
      squamous cells of undetermined significance (ASCUS) or more severe. All
      statistical tests were two-sided. RESULTS: Among HPV-positive women, informed
      cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of
      85.6% (95% confidence interval [CI] = 76.6 to 92.1), 65.9% (95% CI = 63.1 to
      68.6), 16.2% (95% CI = 13.0 to 19.8), and 1.7 (95% CI = 0.9 to 2.8),
      respectively. Cytology was also associated with subsequent risk of newly
      diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs
      blind cytology obtained by referring to colposcopy and following up only HPV
      positive women who had HPV status-informed cytology greater than or equal to
      ASCUS was 1.58 (95% CI = 1.22 to 2.01), while the corresponding relative referral
      to colposcopy was 0.95 (95% CI = 0.86 to 1.04). CONCLUSIONS: Cytology informed of
      HPV positivity is more sensitive than blind cytology and could allow longer
      intervals before retesting HPV-positive, cytology-negative women.

PMID- 25568169
TI  - Bioactive polymethylmethacrylate bone cement modified with combinations of
      phosphate group-containing monomers and calcium acetate.
AB  - Bone cement from polymethylmethacrylate powder and methylmethacrylate liquid has
      been successfully demonstrated as artificial material to anchor joint
      replacements in bone. However, it lacks the capability to bond directly to bone,
      so long-term implantation leads to an increased risk of loosening. Bioactive
      materials show better performance in fixation to bone, and the chemical bonding
      depends on bone-like apatite formation. This is triggered by surface reactions
      with body fluid. For these reactions, superficial functional groups like silanol
      (Si-OH) are ideal sites to induce apatite nucleation and the release of Ca(2+)
      ions accelerates the apatite growth. Therefore, incorporation of materials
      containing these key components may provide the cement with apatite-forming
      ability. In this study, phosphoric acid 2-hydroxyethyl methacrylate ester or
      bis[2-(methacryloyloxy)ethyl] phosphate supplying a phosphate group (PO4H2) was
      added into methylmethacrylate liquid, while calcium acetate as a source of Ca(2+)
      ions was mixed into polymethylmethacrylate powder. The influences of the
      combinations on the setting time and compressive strength were also investigated.
      Apatite was formed on the cements modified with 30 mass% of phosphoric acid 2
      hydroxyethyl methacrylate ester or bis[2-(methacryloyloxy)ethyl] phosphate. The
      induction period was shortened with increased amounts of Ca(CH3COO)2. The setting
      time could be controlled by the Ca(CH3COO)2/monomer mass ratio. Faster setting
      was achieved at a ratio close to the mixing ratio of the powder/liquid (2:1), and
      both increases and decreases in the amount of Ca(CH3COO)2 prolonged the setting
      time based on this ratio. The highest compressive strength was 88.8 +/- 2.6 MPa,
      higher than the lowest limit of ISO 5833 but was lower than that of the simulated
      body fluid-soaked reference. The increase of additives caused the decline in
      compressive strength. In view of balancing apatite formation and clinical
      standard, bis[2-(methacryloyloxy)ethyl] phosphate is more suitable as an
      additive, and the optimal modification is a combination of 30 mass% of bis[2
      (methacryloyloxy)ethyl] phosphate and 20 mass% of Ca(CH3COO)2. 

PMID- 25568171
TI  - Rickshaw scarf strangulation.
AB  - This is a rare case report of delayed onset of symptoms and survival from
      accidental strangulation by a scarf causing "Isadora Duncan syndrome". In 1929,
      the dancer Isadora Duncan died from strangulation and carotid artery insult when
      her billowing scarf caught in the wheels of a motor vehicle in which she was
      travelling. Cycle-propelled rickshaws are popular for short taxi journeys in many
      south Asian countries, particularly India. The case is presented of a woman who
      sustained accidental strangulation with a scarf in the same way as Isadora
      Duncan. The patient was successfully resuscitated and recovered with no
      neurological deficit. It is believed that this is the first recorded case of such
      delayed onset of symptoms and third recorded survival from this condition. 

PMID- 25568172
TI  - Ethnic variations in the provision of biologic therapy for Crohn's disease: a
      Freedom of Information study.
AB  - In this study, we investigate whether the provision of biologic therapy for
      Crohn's disease is equitable across South Asian and English groups in NHS Trusts,
      which serve areas with significant ethnic variation. Data were requested from 10
      NHS Trusts using a Freedom of Information (FOI) approach. Details of numbers of
      patients by ethnicity treated with infliximab or adalumimab for Crohn's disease
      between 2010 and 2012 were requested. Using population-based estimates of disease
      prevalence and Census data on population structure, observed and expected numbers
      who should have received treatment were calculated. In three Trusts, the number
      of South Asian patients who received such treatment was significantly less than
      British/White patients. These were: Pennine Acute Hospitals NHS Trust covering
      Oldham and North Manchester, Barking, Havering & Redbridge University Hospitals
      NHS Trust and University Hospitals of Leicester NHS Trust. The study is limited
      by several factors: 1. The only data available on prevalence in both English and
      South Asian communities comes from Leicester and was published in 1993. More
      recent data suggests that the prevalence of Crohn's disease now approaches
      150/10(5) compared to the 76/10(5) for English patients which was recorded in
      Leicester. However, the two subsequent studies on prevalence which were published
      in 2000 from the North of England and 2010 from Scotland do not provide a
      breakdown by ethnicity. 2. The data were collected by administrative staff using
      a variety of approaches to their Trust's data bases and so the techniques used in
      each Trust are not comparable. In addition, studies from elsewhere suggest that
      the quality of FOI data is affected by the motivation of staff who collect the
      data. 3. With the exception of Leicester, there was no quality check on the
      accuracy of the data. In Leicester, 139 patients were on a register of biologic
      therapy and this compared with 343 patients reported by the FOI request. However,
      the proportions of patients by type of treatment and by ethnicity were comparable
      in the two data sets. This suggests that the data on ethnic differences reported
      by the FOI study reflects real differences. Clearly, there are South Asian
      communities where patients with Crohn's disease appear not to receive appropriate
      treatment in the form of biologics, and the reasons behind this need further
      consideration and investigation. We need to develop robust methods of monitoring
      the provision of biologic therapy across ethnic groups and communities. It is
      unacceptable for there to be a difference based on such grounds.

PMID- 25568170
TI  - Osterix regulates tooth root formation in a site-specific manner.
AB  - Bone and dentin share similar biochemical compositions and physiological
      properties. Dentin, a major tooth component, is formed by odontoblasts; in
      contrast, bone is produced by osteoblasts. Osterix (Osx), a zinc finger
      containing transcription factor, has been identified as an essential regulator of
      osteoblast differentiation and bone formation. However, it has been difficult to
      establish whether Osx functions in odontoblast differentiation and dentin
      formation. To understand the role of Osx in dentin formation, we analyzed mice in
      which Osx was subjected to tissue-specific ablation under the control of either
      the Col1a1 or the OC promoter. Two independent Osx conditional knockout mice
      exhibited similar molar abnormalities. Although no phenotype was found in the
      crowns of these teeth, both mutant lines exhibited short molar roots due to
      impaired root elongation. Furthermore, the interradicular dentin in these mice
      showed severe hypoplastic features, which were likely caused by disruptions in
      odontoblast differentiation and dentin formation. These phenotypes were closely
      related to the temporospatial expression pattern of Osx during tooth development.
      These findings indicate that Osx is required for root formation by regulating
      odontoblast differentiation, maturation, and root elongation. Cumulatively, our
      data strongly indicate that Osx is a site-specific regulator in tooth root
      formation. 

PMID- 25568173
TI  - Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney
      Disorders.
AB  - The critical role of genetic and epigenetic factors in the pathogenesis of kidney
      disorders is gradually becoming clear, and the need for disease models that
      recapitulate human kidney disorders in a personalized manner is paramount. In
      this study, we describe a method to select and amplify renal progenitor cultures
      from the urine of patients with kidney disorders. Urine-derived human renal
      progenitors exhibited phenotype and functional properties identical to those
      purified from kidney tissue, including the capacity to differentiate into tubular
      cells and podocytes, as demonstrated by confocal microscopy, Western blot
      analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage
      tracing studies performed with conditional transgenic mice, in which podocytes
      are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were
      subjected to doxorubicin nephropathy demonstrated that renal progenitors are the
      only urinary cell population that can be amplified in long-term culture. To
      validate the use of these cells for personalized modeling of kidney disorders,
      renal progenitors were obtained from (1) the urine of children with nephrotic
      syndrome and carrying potentially pathogenic mutations in genes encoding for
      podocyte proteins and (2) the urine of children without genetic alterations, as
      validated by next-generation sequencing. Renal progenitors obtained from patients
      carrying pathogenic mutations generated podocytes that exhibited an abnormal
      cytoskeleton structure and functional abnormalities compared with those obtained
      from patients with proteinuria but without genetic mutations. The results of this
      study demonstrate that urine-derived patient-specific renal progenitor cultures
      may be an innovative research tool for modeling of genetic kidney disorders.

PMID- 25568175
TI  - From Patient to Dish and Back Again: Are We There Yet?

PMID- 25568174
TI  - Podocyte Number in Children and Adults: Associations with Glomerular Size and
      Numbers of Other Glomerular Resident Cells.
AB  - Increases in glomerular size occur with normal body growth and in many pathologic
      conditions. In this study, we determined associations between glomerular size and
      numbers of glomerular resident cells, with a particular focus on podocytes.
      Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4
      children (<=3 years old) to define baseline values of early life and 12 adults
      (>=18 years old), were collected at autopsy in Jackson, Mississippi. We used a
      combination of immunohistochemistry, confocal microscopy, and design-based
      stereology to estimate individual glomerular volume (IGV) and numbers of
      podocytes, nonepithelial cells (NECs; tuft cells other than podocytes), and
      parietal epithelial cells (PECs). Podocyte density was calculated. Data are
      reported as medians and interquartile ranges (IQRs). Glomeruli from children were
      small and contained 452 podocytes (IQR=335-502), 389 NECs (IQR=265-498), and 146
      PECs (IQR=111-206). Adult glomeruli contained significantly more cells than
      glomeruli from children, including 558 podocytes (IQR=431-746; P<0.01), 1383 NECs
      (IQR=998-2042; P<0.001), and 367 PECs (IQR=309-673; P<0.001). However, large
      adult glomeruli showed markedly lower podocyte density (183 podocytes per 10(6)
      um(3)) than small glomeruli from adults and children (932 podocytes per 10(6)
      um(3); P<0.001). In conclusion, large adult glomeruli contained more podocytes
      than small glomeruli from children and adults, raising questions about the origin
      of these podocytes. The increased number of podocytes in large glomeruli does not
      match the increase in glomerular size observed in adults, resulting in relative
      podocyte depletion. This may render hypertrophic glomeruli susceptible to
      pathology. 

PMID- 25568176
TI  - Galectin-3, Renal Function, and Clinical Outcomes: Results from the LURIC and 4D
      Studies.
AB  - Galectin-3 has been linked to incident renal disease, experimental renal
      fibrosis, and nephropathy. However, the association among galectin-3, renal
      function, and adverse outcomes has not been described. We studied this
      association in two large cohorts of patients over a broad range of renal
      function. We measured galectin-3 concentrations in baseline samples from the
      German Diabetes mellitus Dialysis (4D) study (1168 dialysis patients with type 2
      diabetes mellitus) and the Ludwigshafen Risk and Cardiovascular Health (LURIC)
      study (2579 patients with coronary angiograms). Patients were stratified into
      three groups: eGFR of >=90 ml/min per 1.73 m(2), 60-89 ml/min per 1.73 m(2), and
      <60 ml/min per 1.73 m(2). We correlated galectin-3 concentrations with
      demographic, clinical, and biochemical parameters. The association of galectin-3
      with clinical end points was assessed by Cox proportional hazards regression
      within 10 years (LURIC) or 4 years (4D) of follow-up. Mean+/-SD galectin-3
      concentrations were 12.8+/-4.0 ng/ml (eGFR>=90 ml/min per 1.73 m(2)), 15.6+/-5.4
      ng/ml (eGFR 60-89 ml/min per 1.73 m(2)), 23.1+/-9.9 ng/ml (eGFR<60 ml/min per
      1.73 m(2)), and 54.1+/-19.6 ng/ml (dialysis patients of the 4D study). Galectin-3
      concentration was significantly associated with clinical end points in
      participants with impaired kidney function, but not in participants with normal
      kidney function. Per SD increase in log-transformed galectin-3 concentration, the
      risks of all-cause mortality, cardiovascular mortality, and fatal infection
      increased significantly. In dialysis patients, galectin-3 was associated with the
      combined end point of cardiovascular events. In conclusion, galectin-3
      concentrations increased with progressive renal impairment and independently
      associated with cardiovascular end points, infections, and all-cause death in
      patients with impaired renal function. 

PMID- 25568179
TI  - Rhinoschleroma.
AB  - A 39 year-old man came to our institution because of a five-year history of a
      progressive painful growing mass on his left nostril, which cause airway
      obstruction with ulceration. Because of a suspicion of malignancy, surgery (mass
      resection and subtotal nasal reconstruction) was performed. Histologic samples
      ruled out malignancy, and tissue cultures for fungus and mycobacteria were
      negative, but regular aerobic cultures were positive for Klebsiella
      rhinoscleromatis. The patient was given a six-month regimen of ciprofloxacin, and
      a dramatic improvement was observed. 

PMID- 25568177
TI  - Role of Myeloid-Derived Suppressor Cells in Glucocorticoid-Mediated Amelioration
      of FSGS.
AB  - The mechanism by which glucocorticoids alleviate renal inflammatory disorders
      remains incompletely understood. Here, we report that the efficacy of
      glucocorticoids in ameliorating FSGS depends on the capacity to expand myeloid
      derived suppressor cells (MDSCs). After glucocorticoid treatment, the frequency
      of CD11b(+)HLA-DR(-)CD14(-)CD15(+) MDSCs in peripheral blood rapidly increased in
      patients with glucocorticoid-sensitive FSGS but remained unchanged in patients
      with glucocorticoid-resistant FSGS. The frequency of CD11b(+)Gr-1(+) MDSCs in
      mouse peripheral blood, bone marrow, spleen, kidney-draining lymph nodes (KDLNs),
      and kidney also increased after glucocorticoid treatment. The induced MDSCs from
      glucocorticoid-treated mice strongly suppressed T cells, dendritic cells, and
      macrophages but induced regulatory T cells in spleen, KDLNs, and kidney.
      Moreover, glucocorticoid treatment suppressed doxorubicin-induced T cell
      proliferation, dendritic cell and macrophage infiltration, and proinflammatory
      cytokine production, whereas this protective effect was largely abolished by
      depleting MDSCs using anti-Gr-1 antibody. Finally, the adoptive transfer of
      induced MDSCs into the doxorubicin-treated mice not only confirmed the protective
      role of MDSCs in doxorubicin-induced renal injury but also showed that the
      transferred MDSCs rapidly migrated into the lymphocyte-accumulating organs, such
      as the spleen and KDLNs, where they suppressed T cell proliferation. Taken
      together, these results demonstrate that glucocorticoid treatment ameliorates
      FSGS by expanding functional MDSCs and that this rapid elevation of MDSCs in
      peripheral blood may serve as an indicator for predicting the efficacy of
      glucocorticoid treatment. 

PMID- 25568180
TI  - Chronic progressive disseminated histoplasmosis in a Mexican cockfighter.
AB  - We present illustrative images from a Mexican 58-year-old man who had the
      occupation of cockfighting from childhood and presented with chronic progressive
      disseminated histoplasmosis with primarily cutaneous manifestations. 

PMID- 25568178
TI  - Classifying AKI by Urine Output versus Serum Creatinine Level.
AB  - Severity of AKI is determined by the magnitude of increase in serum creatinine
      level or decrease in urine output. However, patients manifesting both oliguria
      and azotemia and those in which these impairments are persistent are more likely
      to have worse disease. Thus, we investigated the relationship of AKI severity and
      duration across creatinine and urine output domains with the risk for RRT and
      likelihood of renal recovery and survival using a large, academic medical center
      database of critically ill patients. We analyzed electronic records from 32,045
      patients treated between 2000 and 2008, of which 23,866 (74.5%) developed AKI. We
      classified patients by levels of serum creatinine and/or urine output according
      to Kidney Disease Improving Global Outcomes staging criteria for AKI. In-hospital
      mortality and RRT rates increased from 4.3% and 0%, respectively, for no AKI to
      51.1% and 55.3%, respectively, when serum creatinine level and urine output both
      indicated stage 3 AKI. Both short- and long-term outcomes were worse when
      patients had any stage of AKI defined by both criteria. Duration of AKI was also
      a significant predictor of long-term outcomes irrespective of severity. We
      conclude that short- and long-term risk of death or RRT is greatest when patients
      meet both the serum creatinine level and urine output criteria for AKI and when
      these abnormalities persist. 

PMID- 25568181
TI  - Infection by Leptospira spp. in cattle in a tropical region, Rio de Janeiro,
      Brazil.

PMID- 25568184
TI  - Prospective study of bacteraemia in acute haemorrhagic diarrhoea syndrome in
      dogs.
AB  - In dogs with idiopathic acute haemorrhagic diarrhoea syndrome (AHDS), a serious
      loss of intestinal mucosal barrier integrity occurs. However, the incidence of
      bacterial translocation in dogs with idiopathic AHDS is not known. Thus, the
      objectives of this prospective study were to identify the incidence of
      bacteraemia, to evaluate the frequency of septic events and the influence of
      bacteraemia on various clinical and laboratory parameters, duration of
      hospitalisation and survival of dogs with idiopathic AHDS. The study included 87
      dogs with idiopathic AHDS. Twenty-one healthy dogs served as control group. To
      evaluate clinical significance of bacterial translocation, blood culture results
      were compared between patients and controls. Clinical and laboratory parameters
      were compared between patients with positive and negative blood cultures. There
      was no significant difference in either incidence of bacteraemia between patients
      with idiopathic AHDS (11 per cent) and controls (14 per cent) or in severity of
      clinical signs, laboratory parameters, duration of hospitalisation or mortality
      between blood culture-positive and culture-negative dogs with idiopathic AHDS.
      The results of this study suggest that the incidence of bacteraemia in dogs with
      idiopathic AHDS is low and not different from that of healthy control dogs.
      Bacteraemia does not influence the clinical course or survival and thus
      antibiotic treatment is not indicated to prevent sepsis. 

PMID- 25568185
TI  - RacGAP1 expression, increasing tumor malignant potential, as a predictive
      biomarker for lymph node metastasis and poor prognosis in colorectal cancer.
AB  - Rac GTPase-activating protein (RacGAP) 1 plays a key role in controlling various
      cellular phenomena including cytokinesis, transformation, invasive migration and
      metastasis. This study investigated the function and clinical significance of
      RacGAP1 expression in colorectal cancer (CRC). The intrinsic functions of RacGAP1
      in CRC cells were analyzed using small interfering RNA (siRNA). We analyzed
      RacGAP1 mRNA expression in surgical specimens from 193 CRC patients (Cohort 1) by
      real-time PCR. Finally, we validated RacGAP1 protein expression using formalin
      fixed paraffin-embedded samples from 298 CRC patients (Cohort 2) by
      immunohistochemistry. Reduced RacGAP1 expression by siRNA in CRC cell lines
      showed significantly decreased cellular proliferation, migration and invasion. In
      Cohort 1, RacGAP1 expression in CRC was significantly higher than in adjacent
      normal mucosa and increased according to tumor node metastasis stage progression.
      High RacGAP1 expression in tumors was significantly associated with progression
      and prognosis. In Cohort 2, RacGAP1 protein was overexpressed mainly in the
      nuclei of CRC cells; however, its expression was scarcely observed in normal
      colorectal mucosa. RacGAP1 protein expression was significantly higher in CRC
      patients with higher T stage, vessel invasion and lymph node and distant
      metastasis. Increased expression of RacGAP1 protein was significantly associated
      with poor disease-free and overall survival. Multivariate analyses revealed that
      high RacGAP1 expression was an independent predictive marker for lymph node
      metastasis, recurrence and poor prognosis in CRC. Our data provide novel evidence
      for the biological and clinical significance of RacGAP1 as a potential biomarker
      for identifying patients with lymph node metastasis and poor prognosis in CRC. 

PMID- 25568183
TI  - beta-catenin promotes regulatory T-cell responses in tumors by inducing vitamin A
      metabolism in dendritic cells.
AB  - Tumors actively suppress antitumor immunity, creating formidable barriers to
      successful cancer immunotherapy. The molecular mechanisms underlying tumor
      induced immune tolerance are largely unknown. In the present study, we show that
      dendritic cells (DC) in the tumor microenvironment acquire the ability to
      metabolize vitamin A to produce retinoic acid (RA), which drives regulatory T
      cell responses and immune tolerance. Tolerogenic responses were dependent on
      induction of vitamin A-metabolizing enzymes via the beta-catenin/T-cell factor
      (TCF) pathway in DCs. Consistent with this observation, DC-specific deletion of
      beta-catenin in mice markedly reduced regulatory T-cell responses and delayed
      melanoma growth. Pharmacologic inhibition of either vitamin A-metabolizing
      enzymes or the beta-catenin/TCF4 pathway in vivo had similar effects on tumor
      growth and regulatory T-cell responses. Hence, beta-catenin/TCF4 signaling
      induces local regulatory DC and regulatory T-cell phenotypes via the RA pathway,
      identifying this pathway as an important target for anticancer immunotherapy.

PMID- 25568186
TI  - Characterization of mAbs to chicken anemia virus and epitope mapping on its viral
      protein, VP1.
AB  - Three (MoCAV/F2, MoCAV/F8 and MoCAV/F11) of four mouse mAbs established against
      the A2/76 strain of chicken anemia virus (CAV) showed neutralization activity.
      Immunoprecipitation showed a band at ~50 kDa in A2/76-infected cell lysates by
      neutralizing mAbs, corresponding to the 50 kDa capsid protein (VP1) of CAV, and
      the mAbs reacted with recombinant VP1 proteins expressed in Cos7 cells. MoCAV/F2
      and MoCAV/F8 neutralized the 14 CAV strains tested, whereas MoCAV/F11 did not
      neutralize five of the strains, indicating distinct antigenic variation amongst
      the strains. In blocking immunofluorescence tests with the A2/76-infected cells,
      binding of MoCAV/F11 was not inhibited by the other mAbs. MoCAV/F2 inhibited the
      binding of MoCAV/F8 to the antigens and vice versa, suggesting that the two mAbs
      recognized the same epitope. However, mutations were found in different parts of
      VP1 of the escape mutants of each mAb: EsCAV/F2 (deletion of T89+A90), EsCAV/F8
      (I261T) and EsCAV/F11 (E144G). Thus, the epitopes recognized by MoCAV/F2 and
      MoCAV/F8 seemed to be topographically close in the VP1 structure, suggesting that
      VP1 has at least two different neutralizing epitopes. However, MoCAV/F8 did not
      react with EsCAV/F2 or EsCAV/F8, suggesting that binding of MoCAV/F8 to the
      epitope requires coexistence of the epitope recognized by MoCAV/F2. In addition,
      MoCAV/F2, with a titre of 1 : 12 800 to the parent strain, neutralized EsCAV/F2
      and EsCAV/F8 with low titres of 32 and 152, respectively. The similarity of the
      reactivity of MoCAV/F2 and MoCAV/F8 to VP1 may also suggest the existence of a
      single epitope recognized by these mAbs.

PMID- 25568188
TI  - Mental health and wellbeing.

PMID- 25568191
TI  - Letter to the editor. The ten commandments of good measurement.

PMID- 25568187
TI  - Hamburger polyomaviruses.
AB  - Epidemiological studies have suggested that consumption of beef may correlate
      with an increased risk of colorectal cancer. One hypothesis to explain this
      proposed link might be the presence of a carcinogenic infectious agent capable of
      withstanding cooking. Polyomaviruses are a ubiquitous family of thermostable non
      enveloped DNA viruses that are known to be carcinogenic. Using virion enrichment,
      rolling circle amplification (RCA) and next-generation sequencing, we searched
      for polyomaviruses in meat samples purchased from several supermarkets. Ground
      beef samples were found to contain three polyomavirus species. One species,
      bovine polyomavirus 1 (BoPyV1), was originally discovered as a contaminant in
      laboratory FCS. A previously unknown species, BoPyV2, occupies the same clade as
      human Merkel cell polyomavirus and raccoon polyomavirus, both of which are
      carcinogenic in their native hosts. A third species, BoPyV3, is related to human
      polyomaviruses 6 and 7. Examples of additional DNA virus families, including
      herpesviruses, adenoviruses, circoviruses and gyroviruses were also detected
      either in ground beef samples or in comparison samples of ground pork and ground
      chicken. The results suggest that the virion enrichment/RCA approach is suitable
      for random detection of essentially any DNA virus with a detergent-stable capsid.
      It will be important for future studies to address the possibility that animal
      viruses commonly found in food might be associated with disease. 

PMID- 25568193
TI  - Mind, the mental health charity: improving maternal mental wellbeing.

PMID- 25568192
TI  - RSPH Health and Wellbeing Awards.

PMID- 25568194
TI  - Mental Health First Aid: addressing mental health as a public health priority.

PMID- 25568195
TI  - Because you're worth it.

PMID- 25568196
TI  - What can be done about the social determinants of mental health?

PMID- 25568197
TI  - 'Mind Your Own Business' - how can we best support employers to improve the
      mental health of their employees?

PMID- 25568198
TI  - Improving mental wellbeing for survivors of childhood abuse and neglect:
      psychological healing and education course in prisons.

PMID- 25568199
TI  - Collective wellbeing in public mental health.

PMID- 25568200
TI  - Emotional wellbeing and mental health: an exploration into health promotion in
      young people and families.
AB  - AIMS: Promoting mental health and emotional wellbeing (EWB) in children and young
      people (YP) is vitally important for their psycho-social development. Critical
      review of the literature reveals a dearth of research that has explored the
      perspective of the child, adolescent or adult in this concept, with much research
      being intervention focused and promoted at crisis level. The current study aims
      to address this gap in understanding of young persons' and parents' perspectives.
      METHOD: A small-scale, exploratory qualitative study was conducted with YP, and
      parents of YP aimed at exploring the meaning of EWB and how it could be promoted.
      Data were collected via focus groups with 15 YP (aged 18-24 years) and 15
      interviews with parents of a different group of YP. RESULTS: Study participants
      identified key constructs for good EWB as stability, coping ability, happiness,
      confidence, balance, empathy and being grounded. Feeling comfortable with self,
      managing and controlling emotions and having the confidence to persevere with
      challenges were all felt to contribute to a positive sense of EWB. Sources of
      support were overwhelmingly cited as family and friends, with schools identified
      as a potentially good environment for supporting and promoting the EWB of pupils.
      Participants stressed the need for a positive attitude change towards YP,
      advocating this as promoting a sense of belonging and community citizenship. A
      lay-informed 'recipe' for successful EWB promotion is drawn out, centred on the
      core goal of raising awareness and understanding of YP's EWB, in the YP
      themselves, their parents, schools and the wider community. CONCLUSIONS: This
      research provides key messages for society, policy makers, education and public
      health and healthcare practitioners for integration into the delivery of services
      for YP and families that include education on supporting EWB, activities for YP
      and a multi-agency approach to supporting families within the community.

PMID- 25568201
TI  - Help for heroes? Evaluating a case management programme for ex-service personnel
      in the United Kingdom.
AB  - AIMS: There is increasing recognition of the health and social needs of ex
      service personnel, but the UK evidence base on interventions is small. This
      article presents the findings from an evaluation of a vocational case management
      programme co-funded by the National Health Service (NHS) to prevent ill health
      among ex-service personnel. METHODS: Qualitative, semi-structured interviews with
      15 ex-service personnel were conducted. Five interviews with case management
      staff were also undertaken. Data were transcribed, thematically coded and
      analysed using NVivo. RESULTS: Ex-service personnel valued the service and
      consistently highlighted 'being listened to', 'being made to feel valued by
      programme staff', 'having their problems taken seriously' and 'being treated as
      an individual' as the most valuable aspects of the programme. Respondents
      particularly valued the personal support that case managers provided and the
      environment in which the service was delivered. CONCLUSION: Case management is a
      viable way in which the military, health professionals and support services can
      provide ongoing support for ex-service personnel in transitioning successfully to
      civilian life.

PMID- 25568203
TI  - Synthetic Toll-like receptor 4 (TLR4) and TLR7 ligands as influenza virus vaccine
      adjuvants induce rapid, sustained, and broadly protective responses.
AB  - Current vaccines against influenza virus infection rely on the induction of
      neutralizing antibodies targeting the globular head of the viral hemagglutinin
      (HA). Protection against seasonal antigenic drift or sporadic pandemic outbreaks
      requires further vaccine development to induce cross-protective humoral
      responses, potentially to the more conserved HA stalk region. Here, we present a
      novel viral vaccine adjuvant comprised of two synthetic ligands for Toll-like
      receptor 4 (TLR4) and TLR7. 1Z105 is a substituted pyrimido[5,4-b]indole specific
      for the TLR4-MD2 complex, and 1V270 is a phospholipid-conjugated TLR7 agonist.
      Separately, 1Z105 induces rapid Th2-associated IgG1 responses, and 1V270 potently
      generates Th1 cellular immunity. 1Z105 and 1V270 in combination with recombinant
      HA from the A/Puerto Rico/8/1934 strain (rPR/8 HA) effectively induces rapid and
      sustained humoral immunity that is protective against lethal challenge with a
      homologous virus. More importantly, immunization with the combined adjuvant and
      rPR/8 HA, a commercially available split vaccine, or chimeric rHA antigens
      significantly improves protection against both heterologous and heterosubtypic
      challenge viruses. Heterosubtypic protection is associated with broadly reactive
      antibodies to HA stalk epitopes. Histological examination and cytokine profiling
      reveal that intramuscular (i.m.) administration of 1Z105 and 1V270 is less
      reactogenic than a squalene-based adjuvant, AddaVax. In summary, the combination
      of 1Z105 and 1V270 with a recombinant HA induces rapid, long-lasting, and
      balanced Th1- and Th2-type immunity; demonstrates efficacy in a variety of murine
      influenza virus vaccine models assaying homologous, heterologous, and
      heterosubtypic challenge viruses; and has an excellent safety profile.
      IMPORTANCE: Novel adjuvants are needed to enhance immunogenicity and increase the
      protective breadth of influenza virus vaccines to reduce the seasonal disease
      burden and ensure pandemic preparedness. We show here that the combination of
      synthetic Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for
      recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity
      that is protective against influenza viruses in homologous, heterologous, and
      heterosubtypic challenge models. Combining TLR4 and TLR7 ligands balances Th1-
      and Th2-type immune responses for long-lived cellular and neutralizing humoral
      immunity against the viral hemagglutinin. The combined adjuvant has an attractive
      safety profile and the potential to augment seasonal-vaccine breadth, contribute
      to a broadly neutralizing universal vaccine formulation, and improve response
      time in an emerging pandemic.

PMID- 25568204
TI  - Conserved motifs in a tombusvirus polymerase modulate genome replication,
      subgenomic transcription, and amplification of defective interfering RNAs.
AB  - The replication of plus-strand RNA virus genomes is mediated by virally encoded
      RNA-dependent RNA polymerases (RdRps). We have investigated the role of the C
      proximal region in the RdRp of tomato bushy stunt virus (TBSV) in mediating viral
      RNA synthesis. TBSV is the prototype species in the genus Tombusvirus, family
      Tombusviridae, and its RdRp is responsible for replicating the viral genome,
      transcribing two subgenomic mRNAs, and supporting replication of defective
      interfering RNAs. Comparative sequence analysis of the RdRps of tombusvirids
      identified three highly conserved motifs in their C-proximal regions, and these
      sequences were subsequently targeted for mutational analysis in TBSV. The results
      revealed that these motifs are important for (i) synthesizing viral genomic RNA
      and subgenomic mRNAs, (ii) facilitating plus- and/or minus-strand synthesis, and
      (iii) modulating trans-replication of a defective interfering RNA. These motifs
      were also found to be conserved in other plant viruses as well as in a fungal and
      insect virus. The collective findings are discussed in relation to viral RNA
      synthesis and taxonomy. IMPORTANCE: Little is currently known about the structure
      and function of the viral polymerases that replicate the genomes of RNA plant
      viruses. Tombusviruses, the prototype of the tombusvirids, have been used as
      model plus-strand RNA plant viruses for understanding many of the steps in the
      infectious process; however, their polymerases remain poorly characterized. To
      help address this issue, the function of the C-terminal region of the polymerase
      of a tombusvirus was investigated. Three conserved motifs were identified and
      targeted for mutational analysis. The results revealed that these polymerase
      motifs are important for determining what type of viral RNA is produced,
      facilitating different steps in viral RNA production, and amplifying subgenomic
      RNA replicons. Accordingly, the C-terminal region of the tombusvirus polymerase
      is needed for a variety of fundamental activities. Furthermore, as these motifs
      are also present in distantly related viruses, the significance of these results
      extends beyond tombusvirids.

PMID- 25568205
TI  - Vpu is the main determinant for tetraspanin downregulation in HIV-1-infected
      cells.
AB  - Tetraspanins constitute a family of cellular proteins that organize various
      membrane-based processes. Several members of this family, including CD81, are
      actively recruited by HIV-1 Gag to viral assembly and release sites. Despite
      their enrichment at viral exit sites, the overall levels of tetraspanins are
      decreased in HIV-1-infected cells. Here, we identify Vpu as the main viral
      determinant for tetraspanin downregulation. We also show that reduction of CD81
      levels by Vpu is not a by-product of CD4 or BST-2/tetherin elimination from the
      surfaces of infected cells and likely occurs through an interaction between Vpu
      and CD81. Finally, we document that Vpu-mediated downregulation of CD81 from the
      surfaces of infected T cells can contribute to preserving the infectiousness of
      viral particles, thus revealing a novel Vpu function that promotes virus
      propagation by modulating the host cell environment. IMPORTANCE: The HIV-1
      accessory protein Vpu has previously been shown to downregulate various host cell
      factors, thus helping the virus to overcome restriction barriers, evade immune
      attack, and maintain the infectivity of viral particles. Our study identifies
      tetraspanins as an additional group of host factors whose expression at the
      surfaces of infected cells is lowered by Vpu. While the downregulation of these
      integral membrane proteins, including CD81 and CD82, likely affects more than one
      function of HIV-1-infected cells, we document that Vpu-mediated lowering of CD81
      levels in viral particles can be critical to maintaining their infectiousness.

PMID- 25568207
TI  - Stability of structured Kaposi's sarcoma-associated herpesvirus ORF57 protein is
      regulated by protein phosphorylation and homodimerization.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 plays an essential role in
      KSHV lytic infection by promoting viral gene expression at the
      posttranscriptional level. Using bioinformatic and biochemical approaches, we
      determined that ORF57 contains two structurally and functionally distinct
      domains: a disordered nonstructural N-terminal domain (amino acids [aa] 1 to 152)
      and a structured alpha-helix-rich C-terminal domain (aa 153 to 455). The N
      terminal domain mediates ORF57 interaction with several RNA-protein complexes
      essential for ORF57 to function. The N-terminal phosphorylation by cellular
      casein kinase II (CKII) at S21, T32, and S43, and other cellular kinases at S95
      and S97 residues in proximity of the caspase-7 cleavage site, 30-DETD-33,
      inhibits caspase-7 digestion of ORF57. The structured C-terminal domain mediates
      homodimerization of ORF57, and the critical region for this function was mapped
      carefully to alpha-helices 7 to 9. Introduction of point mutations into alpha
      helix 7 at ORF57 aa 280 to 299, a region highly conserved among ORF57 homologues
      from other herpesviruses, inhibited ORF57 homodimerization and led to proteasome
      mediated degradation of ORF57 protein. Thus, homodimerization of ORF57 via its C
      terminus prevents ORF57 from degrading and allows two structure-free N termini of
      the dimerized ORF57 to work coordinately for host factor interactions, leading to
      productive KSHV lytic infection and pathogenesis. IMPORTANCE: KSHV is a human
      oncogenic virus linked to the development of several malignancies. KSHV-mediated
      oncogenesis requires both latent and lytic infection. The KSHV ORF57 protein is
      essential for KSHV lytic replication, as it regulates the expression of viral
      lytic genes at the posttranscriptional level. This report provides evidence that
      the structural conformation of the ORF57 protein plays a critical role in
      regulation of ORF57 stability. Phosphorylation by CKII on the identified
      serine/threonine residues at the N-terminal unstructured domain of ORF57 prevents
      its digestion by caspase-7. The C-terminal domain of ORF57, which is rich in
      alpha-helices, contributes to homodimerization of ORF57 to prevent proteasome
      mediated protein degradation. Elucidation of the ORF57 structure not only enables
      us to better understand ORF57 stability and functions but also provides an
      important tool for us to modulate ORF57's activity with the aim to inhibit KSHV
      lytic replication.

PMID- 25568206
TI  - Impact of the adenoviral E4 Orf3 protein on the activity and posttranslational
      modification of p53.
AB  - Our previous studies have established that the p53 populations that accumulate in
      normal human cells exposed to etoposide or infected by an E1B 55-kDa protein-null
      mutant of human adenovirus type 5 carry a large number of posttranslational
      modifications at numerous residues (C. J. DeHart, J. S. Chahal, S. J. Flint, and
      D. H. Perlman, Mol Cell Proteomics 13:1-17, 2014,
      http://dx.doi.org/10.1074/mcp.M113.030254). In the absence of this E1B protein,
      the p53 transcriptional program is not induced, and it has been reported that the
      viral E4 Orf3 protein inactivates p53 (C. Soria, F. E. Estermann, K. C.
      Espantman, and C. C. O'Shea, Nature 466:1076-1081, 2010,
      http://dx.doi.org/10.1038/nature09307). As the latter protein disrupts nuclear
      Pml bodies, sites at which p53 is modified, we used mass spectrometry to
      catalogue the posttranscriptional modifications of the p53 population that
      accumulates when neither the E1B 55-kDa nor the E4 Orf3 protein is made in
      infected cells. Eighty-five residues carrying 163 modifications were identified.
      The overall patterns of posttranslational modification of this population and p53
      present in cells infected by an E1B 55-kDa-null mutant were similar. The
      efficiencies with which the two forms of p53 bound to a consensus DNA recognition
      sequence could not be distinguished and were lower than that of transcriptionally
      active p53. The absence of the E4 Orf3 protein increased expression of several
      p53-responsive genes when the E1B protein was also absent from infected cells.
      However, expression of these genes did not attain the levels observed when p53
      was activated in response to etoposide treatment and remained lower than those
      measured in mock-infected cells. IMPORTANCE: The tumor suppressor p53, a master
      regulator of cellular responses to stress, is inactivated and destroyed in cells
      infected by species C human adenoviruses, such as type 5. It is targeted for
      proteasomal degradation by the action of a virus-specific E3 ubiquitin ligase
      that contains the viral E1B 55-kDa and E4 Orf6 proteins, while the E4 Orf3
      protein has been reported to block its ability to stimulate expression of p53
      dependent genes. The comparisons reported here of the posttranslational
      modifications and activities of p53 populations that accumulate in infected
      normal human cells in the absence of both mechanisms of inactivation or of only
      the E3 ligase revealed little impact of the E4 Orf3 protein. These observations
      indicate that E4 Orf3-dependent disruption of Pml bodies does not have a major
      effect on the pattern of p53 posttranslational modifications in adenovirus
      infected cells. Furthermore, they suggest that one or more additional viral
      proteins contribute to blocking p53 activation and the consequences that are
      deleterious for viral reproduction, such as apoptosis or cell cycle arrest.

PMID- 25568208
TI  - Characterization of dengue virus NS4A and NS4B protein interaction.
AB  - Flavivirus replication is mediated by a membrane-associated replication complex
      where viral membrane proteins NS2A, NS2B, NS4A, and NS4B serve as the scaffold
      for the replication complex formation. Here, we used dengue virus serotype 2
      (DENV-2) as a model to characterize viral NS4A-NS4B interaction. NS4A interacts
      with NS4B in virus-infected cells and in cells transiently expressing NS4A and
      NS4B in the absence of other viral proteins. Recombinant NS4A and NS4B proteins
      directly bind to each other with an estimated Kd (dissociation constant) of 50
      nM. Amino acids 40 to 76 (spanning the first transmembrane domain, consisting of
      amino acids 50 to 73) of NS4A and amino acids 84 to 146 (also spanning the first
      transmembrane domain, consisting of amino acids 101 to 129) of NS4B are the
      determinants for NS4A-NS4B interaction. Nuclear magnetic resonance (NMR) analysis
      suggests that NS4A residues 17 to 80 form two amphipathic helices (helix alpha1,
      comprised of residues 17 to 32, and helix alpha2, comprised of residues 40 to 47)
      that associate with the cytosolic side of endoplasmic reticulum (ER) membrane and
      helix alpha3 (residues 52 to 75) that transverses the ER membrane. In addition,
      NMR analysis identified NS4A residues that may participate in the NS4A-NS4B
      interaction. Amino acid substitution of these NS4A residues exhibited distinct
      effects on viral replication. Three of the four NS4A mutations (L48A, T54A, and
      L60A) that affected the NS4A-NS4B interaction abolished or severely reduced viral
      replication; in contrast, two NS4A mutations (F71A and G75A) that did not affect
      NS4A-NS4B interaction had marginal effects on viral replication, demonstrating
      the biological relevance of the NS4A-NS4B interaction to DENV-2 replication.
      Taken together, the study has provided experimental evidence to argue that
      blocking the NS4A-NS4B interaction could be a potential antiviral approach.
      IMPORTANCE: Flavivirus NS4A and NS4B proteins are essential components of the ER
      membrane-associated replication complex. The current study systematically
      characterizes the interaction between flavivirus NS4A and NS4B. Using DENV-2 as a
      model, we show that NS4A interacts with NS4B in virus-infected cells, in cells
      transiently expressing NS4A and NS4B proteins, or in vitro with recombinant NS4A
      and NS4B proteins. We mapped the minimal regions required for the NS4A-NS4B
      interaction to be amino acids 40 to 76 of NS4A and amino acids 84 to 146 of NS4B.
      NMR analysis revealed the secondary structure of amino acids 17 to 80 of NS4A and
      the NS4A amino acids that may participate in the NS4A-NS4B interaction.
      Functional analysis showed a correlation between viral replication and NS4A-NS4B
      interaction, demonstrating the biological importance of the NS4A-NS4B
      interaction. The study has advanced our knowledge of the molecular function of
      flavivirus NS4A and NS4B proteins. The results also suggest that inhibitors of
      the NS4A-NS4B interaction could be pursued for flavivirus antiviral development.

PMID- 25568209
TI  - Human immunodeficiency virus type 1 employs the cellular dynein light chain 1
      protein for reverse transcription through interaction with its integrase protein.
AB  - In this study, we examined the requirement for host dynein adapter proteins such
      as dynein light chain 1 (DYNLL1), dynein light chain Tctex-type 1 (DYNLT1), and
      p150(Glued) in early steps of human immunodeficiency virus type 1 (HIV-1)
      replication. We found that the knockdown (KD) of DYNLL1, but not DYNLT1 or
      p150(Glued), resulted in significantly lower levels of HIV-1 reverse
      transcription in cells. Following an attempt to determine how DYNLL1 could impact
      HIV-1 reverse transcription, we detected the DYNLL1 interaction with HIV-1
      integrase (IN) but not with capsid (CA), matrix (MA), or reverse transcriptase
      (RT) protein. Furthermore, by mutational analysis of putative DYNLL1 interaction
      motifs in IN, we identified the motifs (52)GQVD and (250)VIQD in IN as essential
      for DYNLL1 interaction. The DYNLL1 interaction-defective IN mutant HIV-1 (HIV
      1IN(Q53A/Q252A)) exhibited impaired reverse transcription. Through further
      investigations, we have also detected relatively smaller amounts of particulate
      CA in DYNLL1-KD cells or in infections with HIV-1IN(Q53A/Q252A) mutant virus.
      Overall, our study demonstrates the novel interaction between HIV-1 IN and
      cellular DYNLL1 proteins and suggests the requirement of this virus-cell
      interaction for proper uncoating and efficient reverse transcription of HIV-1.
      IMPORTANCE: Host cellular DYNLL1, DYNLT1, and p150(Glued) proteins have been
      implicated in the replication of several viruses. However, their roles in HIV-1
      replication have not been investigated. For the first time, we demonstrated that
      during viral infection, HIV-1 IN interacts with DYNLL1, and their interaction was
      found to have a role in proper uncoating and efficient reverse transcription of
      HIV-1. Thus, interaction of IN and DYNLL1 may be a potential target for future
      anti-HIV therapy. Moreover, while our study has evaluated the involvement of IN
      in HIV-1 uncoating and reverse transcription, it also predicts a possible
      mechanism by which IN contributes to these early viral replication steps.

PMID- 25568210
TI  - Identification and characterization of the binding site of the respiratory
      syncytial virus phosphoprotein to RNA-free nucleoprotein.
AB  - The RNA genome of respiratory syncytial virus (RSV) is constitutively
      encapsidated by the viral nucleoprotein N, thus forming a helical nucleocapsid.
      Polymerization of N along the genomic and antigenomic RNAs is concomitant to
      replication and requires the preservation of an unassembled monomeric
      nucleoprotein pool. To this end, and by analogy with Paramyxoviridae and
      Rhabdoviridae, it is expected that the viral phosphoprotein P acts as a chaperone
      protein, forming a soluble complex with the RNA-free form of N (N(0)-P complex).
      Here, we have engineered a mutant form of N that is monomeric, is unable to bind
      RNA, still interacts with P, and could thus mimic the N(0) monomer. We used this
      N mutant, designated N(mono), as a substitute for N(0) in order to characterize
      the P regions involved in the N(0)-P complex formation. Using a series of P
      fragments, we determined by glutathione S-transferase (GST) pulldown assays that
      the N and C termini of P are able to interact with N(mono). We analyzed the
      functional role of amino-terminal residues of P by site-directed mutagenesis,
      using an RSV polymerase activity assay based on a human RSV minireplicon, and
      found that several residues were critical for viral RNA synthesis. Using GST
      pulldown and surface plasmon resonance assays, we showed that these critical
      residues are involved in the interaction between P[1-40] peptide and N(mono) in
      vitro. Finally, we showed that overexpression of the peptide P[1-29] can inhibit
      the polymerase activity in the context of the RSV minireplicon, thus
      demonstrating that targeting the N(0)-P interaction could constitute a potential
      antiviral strategy. IMPORTANCE: Respiratory syncytial virus (RSV) is the leading
      cause of lower respiratory tract illness in infants. Since no vaccine or
      efficient antiviral treatment is available against RSV, it is essential to better
      understand how the viral machinery functions in order to develop new antiviral
      strategies. RSV phosphoprotein P, the main RNA polymerase cofactor, is believed
      to function as a chaperon protein, maintaining N as a nonassembled, RNA-free
      protein (N(0)) competent for RNA encapsidation. In this paper, we provide the
      first evidence, to our knowledge, that the N terminus of P contains a domain that
      binds specifically to this RNA-free form of N. We further show that
      overexpression of a small peptide spanning this region of P can inhibit viral RNA
      synthesis. These findings extend our understanding of the function of RSV RNA
      polymerase and point to a new target for the development of drugs against this
      virus.

PMID- 25568211
TI  - The interface between hepatitis B virus capsid proteins affects self-assembly,
      pregenomic RNA packaging, and reverse transcription.
AB  - Hepatitis B virus (HBV) capsid proteins (Cps) assemble around the pregenomic RNA
      (pgRNA) and viral reverse transcriptase (P). pgRNA is then reverse transcribed to
      double-stranded DNA (dsDNA) within the capsid. The Cp assembly domain, which
      forms the shell of the capsid, regulates assembly kinetics and capsid stability.
      The Cp, via its nucleic acid-binding C-terminal domain, also affects nucleic acid
      organization. We hypothesize that the structure of the capsid may also have a
      direct effect on nucleic acid processing. Using structure-guided design, we made
      a series of mutations at the interface between Cp subunits that change capsid
      assembly kinetics and thermodynamics in a predictable manner. Assembly in cell
      culture mirrored in vitro activity. However, all of these mutations led to
      defects in pgRNA packaging. The amount of first-strand DNA synthesized was
      roughly proportional to the amount of RNA packaged. However, the synthesis of
      second-strand DNA, which requires two template switches, was not supported by any
      of the substitutions. These data demonstrate that the HBV capsid is far more than
      an inert container, as mutations in the assembly domain, distant from packaged
      nucleic acid, affect reverse transcription. We suggest that capsid molecular
      motion plays a role in regulating genome replication. IMPORTANCE: The hepatitis B
      virus (HBV) capsid plays a central role in the virus life cycle and has been
      studied as a potential antiviral target. The capsid protein (Cp) packages the
      viral pregenomic RNA (pgRNA) and polymerase to form the HBV core. The role of the
      capsid in subsequent nucleic acid metabolism is unknown. Here, guided by the
      structure of the capsid with bound antiviral molecules, we designed Cp mutants
      that enhanced or attenuated the assembly of purified Cp in vitro. In cell
      culture, assembly of mutants was consistent with their in vitro biophysical
      properties. However, all of these mutations inhibited HBV replication.
      Specifically, changing the biophysical chemistry of Cp caused defects in pgRNA
      packaging and synthesis of the second strand of DNA. These results suggest that
      the HBV Cp assembly domain potentially regulates reverse transcription, extending
      the activities of the capsid protein beyond its presumed role as an inert
      compartment.

PMID- 25568212
TI  - Contribution of MxB oligomerization to HIV-1 capsid binding and restriction.
AB  - The alpha interferon (IFN-alpha)-inducible restriction factor myxovirus B (MxB)
      blocks HIV-1 infection after reverse transcription but prior to integration. MxB
      binds to the HIV-1 core, which is composed of capsid protein, and this
      interaction leads to inhibition of the uncoating process of HIV-1. Previous
      studies suggested that HIV-1 restriction by MxB requires binding to capsid. This
      work tests the hypothesis that MxB oligomerization is important for the ability
      of MxB to bind to the HIV-1 core. For this purpose, we modeled the structure of
      MxB using the published tertiary structure of MxA. The modeled structure of MxB
      guided our mutagenic studies and led to the discovery of several MxB variants
      that lose the capacity to oligomerize. In agreement with our hypothesis, MxB
      variants that lost the oligomerization capacity also lost the ability to bind to
      the HIV-1 core. MxB variants deficient for oligomerization were not able to block
      HIV-1 infection. Overall, our work showed that oligomerization is required for
      the ability of MxB to bind to the HIV-1 core and block HIV-1 infection.
      IMPORTANCE: MxB is a novel restriction factor that blocks infection of HIV-1. MxB
      is inducible by IFN-alpha, particularly in T cells. The current work studies the
      oligomerization determinants of MxB and carefully explores the contribution of
      oligomerization to capsid binding and restriction. This work takes advantage of
      the current structure of MxA and models the structure of MxB, which is used to
      guide structure-function studies. This work leads to the conclusion that MxB
      oligomerization is important for HIV-1 capsid binding and restriction.

PMID- 25568216
TI  - A systematic review of glomerular hyperfiltration assessment and definition in
      the medical literature.
AB  - BACKGROUND AND OBJECTIVES: Evaluation of glomerular hyperfiltration (GH) is
      difficult; the variable reported definitions impede comparisons between studies.
      A clear and universal definition of GH would help in comparing results of trials
      aimed at reducing GH. This study assessed how GH is measured and defined in the
      literature. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Three databases
      (Embase, MEDLINE, CINAHL) were systematically searched using the terms
      "hyperfiltration" or "glomerular hyperfiltration". All studies reporting a GH
      threshold or studying the effect of a high GFR in a continuous manner against
      another outcome of interest were included. RESULTS: The literature search was
      performed from November 2012 to February 2013 and updated in August 2014. From
      2013 retrieved studies, 405 studies were included. Threshold use to define GH was
      reported in 55.6% of studies. Of these, 88.4% used a single threshold and 11.6%
      used numerous thresholds adapted to participant sex or age. In 29.8% of the
      studies, the choice of a GH threshold was not based on a control group or
      literature references. After 2004, the use of GH threshold use increased
      (P<0.001), but the use of a control group to precisely define that GH threshold
      decreased significantly (P<0.001); the threshold did not differ among pediatric,
      adult, or mixed-age studies. The GH threshold ranged from 90.7 to 175 ml/min per
      1.73 m(2) (median, 135 ml/min per 1.73 m(2)). CONCLUSION: Thirty percent of
      studies did not justify the choice of threshold values. The decrease of GFR in
      the elderly was rarely considered in defining GH. From a methodologic point of
      view, an age- and sex-matched control group should be used to define a GH
      threshold.

PMID- 25568217
TI  - Number and frequency of albuminuria measurements in clinical trials in diabetic
      nephropathy.
AB  - BACKGROUND AND OBJECTIVES: Albuminuria change is often used to assess drug
      efficacy in intervention trials in nephrology. The change is often calculated
      using a variable number of urine samples collected at baseline and end of
      treatment. Yet more albuminuria measurements usually occur. Because albuminuria
      shows a large day-to-day variability, this study assessed to what extent the
      average and the precision of the antialbuminuric drug effect varies with the
      number of urine collections at each visit and the number of follow-up visits.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study used data from three
      randomized intervention trials (Aliskiren Combined with Losartan in Type 2
      Diabetes and Nephropathy, Selective Vitamin D Receptor Activation for Albuminuria
      Lowering, and Residual Albuminuria Lowering with Endothelin Antagonist
      Atrasentan) including patients with type 2 diabetes and macroalbuminuria.
      Albuminuria-lowering drug effects were estimated from one, two, or three urine
      collections at consecutive days before each study visit and reported as
      albuminuria change from baseline to end of treatment or the change over time
      considering an average of all follow-up albuminuria measurements. RESULTS:
      Increasing the number of urine collections for an albuminuria measurement at
      baseline and end of treatment or using all study visits during follow-up did not
      alter the average drug effect. The precision of the drug effect increased
      (decreased SEM) when the number of study visits and the number of urine
      collections per visit were increased. Using all albuminuria measurements at all
      study visits led to a 4- to 6-fold reduction in sample size to detect a 30%
      albuminuria-lowering treatment effect with 80% power compared with using baseline
      and end-of-treatment albuminuria measurements alone. CONCLUSIONS: Increasing the
      number of urine collections per study visit and the number of visits over time
      does not change the average drug effect estimate but markedly increases the
      precision, thereby enhancing statistical power. Thus, clinical trial designs in
      diabetic nephropathy using albuminuria as an end point can be significantly
      improved, leading to smaller sample sizes and less complex trials.

PMID- 25568219
TI  - Vascular access creation before hemodialysis initiation and use: a population
      based cohort study.
AB  - BACKGROUND AND OBJECTIVES: In Canada, approximately 17% of patients use an
      arteriovenous access (fistula or arteriovenous graft) at commencement of
      hemodialysis, despite guideline recommendations promoting its timely creation and
      use. It is unclear if this low pattern of use is attributable to the lack of
      surgical creation or a high nonuse rate. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Using large health care databases in Ontario, Canada, a population
      based cohort of adult patients (>=18 years old) who initiated hemodialysis as
      their first form of RRT between 2001 and 2010 was studied. The aims were to (1)
      estimate the proportion of patients who had an arteriovenous access created
      before starting hemodialysis and the proportion who successfully used it at
      hemodialysis start, (2) test for secular trends in arteriovenous access creation,
      and (3) estimate the effect of late nephrology referral and patient
      characteristics on arteriovenous access creation. RESULTS: There were 17,183
      patients on incident hemodialysis. The mean age was 65.8 years, 60% were men, and
      40% were referred late to a nephrologist; 27% of patients (4556 of 17,183) had
      one or more arteriovenous accesses created, and the median time between
      arteriovenous access creation and hemodialysis start was 184 days. When late
      referrals were excluded, 39% of patients (4007 of 10,291) had one or more
      arteriovenous accesses created, and 27% of patients (2724 of 10,291) used the
      arteriovenous access. Since 2001, there has been a decline in arteriovenous
      access creation before hemodialysis initiation. Women, higher numbers of
      comorbidities, and rural residence were consistently associated with lower rates
      of arteriovenous access creation. These results persisted even after removing
      patients with <6 months nephrology care or who had AKI 6 months before starting
      hemodialysis. CONCLUSIONS: In Canada, arteriovenous access creation before
      hemodialysis initiation is low, even among patients followed by a nephrologist.
      Better understanding of the barriers and influencers of arteriovenous access
      creation is needed to inform both clinical care and guidelines.

PMID- 25568223
TI  - Opponent's comment.

PMID- 25568224
TI  - Opponent's comment.

PMID- 25568218
TI  - Dendritic Cells and Macrophages: Sentinels in the Kidney.
AB  - The mononuclear phagocytes (dendritic cells and macrophages) are closely related
      immune cells with central roles in anti-infectious defense and maintenance of
      organ integrity. The canonical function of dendritic cells is the activation of T
      cells, whereas macrophages remove apoptotic cells and microbes by phagocytosis.
      In the kidney, these cell types form an intricate system of mononuclear
      phagocytes that surveys against injury and infection and contributes to organ
      homeostasis and tissue repair but may also promote progression of CKD. This
      review summarizes the general functions and classification of dendritic cells and
      macrophages in the immune system and recapitulates why overlapping definitions
      and historically separate research have created controversy about their tasks.
      Their roles in acute kidney disease, CKD, and renal transplantation are
      described, and therapeutic strategy to modify these cells for therapeutic
      purposes is discussed. 

PMID- 25568220
TI  - Molecules Great and Small: The Complement System.
AB  - The complement cascade, traditionally considered an effector arm of innate
      immunity required for host defense against pathogens, is now recognized as a
      crucial pathogenic mediator of various kidney diseases. Complement components
      produced by the liver and circulating in the plasma undergo activation through
      the classical and/or mannose-binding lectin pathways to mediate anti-HLA antibody
      initiated kidney transplant rejection and autoantibody-initiated GN, the latter
      including membranous glomerulopathy, antiglomerular basement membrane disease,
      and lupus nephritis. Inherited and/or acquired abnormalities of complement
      regulators, which requisitely limit restraint on alternative pathway complement
      activation, contribute to the pathogenesis of the C3 nephropathies and atypical
      hemolytic uremic syndrome. Increasing evidence links complement produced by
      endothelial cells and/or tubular cells to the pathogenesis of kidney ischemia
      reperfusion injury and progressive kidney fibrosis. Data emerging since the mid
      2000s additionally show that immune cells, including T cells and antigen
      presenting cells, produce alternative pathway complement components during
      cognate interactions. The subsequent local complement activation yields
      production of the anaphylatoxins C3a and C5a, which bind to their respective
      receptors (C3aR and C5aR) on both partners to augment effector T-cell
      proliferation and survival, while simultaneously inhibiting regulatory T-cell
      induction and function. This immune cell-derived complement enhances pathogenic
      alloreactive T-cell immunity that results in transplant rejection and likely
      contributes to the pathogenesis of other T cell-mediated kidney diseases.
      C5a/C5aR ligations on neutrophils have additionally been shown to contribute to
      vascular inflammation in models of ANCA-mediated renal vasculitis. New
      translational immunology efforts along with the development of pharmacologic
      agents that block human complement components and receptors now permit testing of
      the intriguing concept that targeting complement in patients with an assortment
      of kidney diseases has the potential to abrogate disease progression and improve
      patient health.

PMID- 25568226
TI  - Combining progression-free survival and overall survival as a novel composite
      endpoint for glioblastoma trials.
AB  - BACKGROUND: The use of auxiliary endpoints may provide efficiencies for clinical
      trial design, but such endpoints may not have intrinsic clinical relevance or
      clear linkage to more meaningful endpoints. The purpose of this study was to
      generate a novel endpoint that considers both overall survival (OS) and earlier
      events such as progression-free survival (PFS) and determine whether such an
      endpoint could increase efficiency in the design of glioblastoma clinical trials.
      METHODS: Recognizing that the association between PFS and OS varies depending on
      therapy and tumor type, we developed a statistical model to predict OS based on
      PFS as the trial progresses. We then evaluated the efficiency of our model using
      simulations of adaptively randomized trials incorporating PFS and OS
      distributions from prior published trials in neuro-oncology. RESULTS: When
      treatment effects on PFS and OS are concordant, our proposed approach results in
      efficiency gains compared with randomization based on OS alone while sacrificing
      minimal efficiency compared with using PFS as the primary endpoint. When
      treatment effects are limited to PFS, our approach provides randomization
      probabilities that are close to those based on OS alone. CONCLUSION: Use of OS as
      the primary endpoint, combined with statistical modeling of the relationship
      between OS and PFS during the course of the trial, results in more robust and
      efficient trial designs than using either endpoint alone.

PMID- 25568228
TI  - High superficial musculoaponeurotic system facelift with finger-assisted facial
      spaces dissection for Asian patients.
AB  - BACKGROUND: Few facelift methods are designed specifically for Asian patients.
      Because of their characteristic thick skin and flat, wide facial geometry,
      satisfactory facelift results can be difficult to achieve in these patients.
      OBJECTIVES: The authors evaluated outcomes achieved with a high superficial
      musculoaponeurotic system (high-SMAS) facelift with finger-assisted facial spaces
      dissection to rejuvenate the aging Asian face. METHODS: Fifty-three patients
      underwent this facelift procedure. The indication for surgery was typical sagging
      of the face associated with aging; the relative contraindications were previous
      facelift and severe facial atrophy. RESULTS: Mean patient age was 50.7 years.
      Patients received follow-up for a mean of 19 months. In all cases, improvement
      was seen in soft-tissue sagging of the midface and lower face. One patient
      experienced unilateral temporal nerve injury, 3 experienced hematoma, and 2 had
      wound dehiscence. CONCLUSIONS: Understanding surgical anatomy including facial
      layers, spaces, and retaining ligaments is crucial for stable application of
      facelift techniques in Asian patients. Because of the small number of patients
      evaluated in this study and the limited follow-up period, more research is needed
      to define suitable facelift methods for these patients.

PMID- 25568227
TI  - Critical assessment of the morbidity associated with ruptured cerebral
      arteriovenous malformations.
AB  - BACKGROUND: An accurate understanding of the morbidity and mortality associated
      with brain arteriovenous malformation (AVM) hemorrhage is important in
      determining the management of unruptured AVMs. Recent studies suggest this
      morbidity to be lower than assumed. We sought to perform a detailed critical
      assessment of the morbidity associated with ruptured brain AVMs. METHODS: A
      retrospective chart review from a single-center tertiary care medical center was
      performed. Inclusion criteria were patients admitted with intracranial hemorrhage
      caused by a previously untreated AVM. Forty variables were analyzed including
      patient demographics, imaging findings, clinical course, and clinical
      examinations. RESULTS: From 2008 to 2013, of the 51 patients who fit our
      inclusion criteria, we found admission National Institutes of Health Stroke Scale
      (NIHSS) scores of 0, 1-9, and >=10 in 22%, 24%, and 55%, respectively. Hematoma
      location was parenchymal in 33%, intraventricular in 10%, subarachnoid in 4%, and
      combined in 53%. Deep venous drainage was present in 35% of cases and associated
      aneurysms were present in 37%. 43% underwent emergency hematoma evacuation while
      four patients died during their admission. Of those who survived, 74% had
      neurologic deficits upon discharge (NIHSS >=1), with 25.5% of patients having a
      severe deficit (NIHSS >=10). On follow-up, 55% were independent in their daily
      activities of living. CONCLUSIONS: Our assessment of morbidity associated with
      brain AVM rupture is higher than previously assumed and reported. These results
      should be further validated in a larger, more representative sample. An accurate
      understanding of the morbidity associated with AVM rupture is important as more
      patients with unruptured brain AVMs seek consultation.

PMID- 25568229
TI  - Commentary on: High superficial musculoaponeurotic system facelift with finger
      assisted facial spaces dissection for Asian patients.

PMID- 25568230
TI  - Tarsal sling: an essential stitch to prevent scleral show in lower
      blepharoplasty.
AB  - BACKGROUND: Despite its popularity for facial rejuvenation, blepharoplasty has
      been associated with several adverse effects. One of the most common is eyelid
      displacement after lower transcutaneous blepharoplasty. The tarsal sling
      procedure affixes the external portion of the septum (the lateral canthal
      ligament) to the internal orbital wall periosteum with a simple suture. This
      simplified canthopexy decreases the risk of lower eyelid margin displacement.
      OBJECTIVES: The authors sought to determine the effectiveness of the tarsal sling
      technique in preventing lower eyelid malposition. METHODS: A retrospective
      analysis of 40 consecutive patients was conducted. Twenty patients underwent
      standard blepharoplasty (group 1), and 20 underwent blepharoplasty plus tarsal
      sling support (group 2). Pre- and postsurgical positions of the lower eyelid
      margin were compared by quantitative analysis of measurements obtained from
      clinical photographs. RESULTS: Postoperatively, reduction of scleral appearance
      was noted for group 2. Although progressive recovery occurred in this group by 2
      years postoperative, the lower eyelids did not revert to presurgical position,
      and a slight degree of overcorrection remained. The overcorrection was minimal,
      without unpleasant consequences for the patients. In contrast, group 1 patients
      experienced an increase in the distance between the interpupillary line and the
      lateral aspect of the lower eyelid margin after blepharoplasty. Although
      progressive resolution of scleral show occurred by 2 years postoperative,
      recovery was not complete. CONCLUSIONS: Through quantitative analysis, the
      authors demonstrated the effectiveness of a simplified canthopexy procedure.
      Tarsal sling is an easy, quick, and efficacious procedure to prevent eyelid
      malposition after lower blepharoplasty.

PMID- 25568231
TI  - Mattress sutures to remove unwanted convexity and concavity of the nasal tip: 12
      year follow-up.
AB  - Nasal tip bulbosity, or convexity, has been one of the most difficult problems to
      correct during rhinoplasty. Excision of cartilage from the cephalic part of the
      lateral crus has helped. However, complete correction of the deformity is not
      always possible with this maneuver alone. Suture techniques have also helped to
      improve outcomes. Twelve years ago, the lateral crus mattress suture was
      introduced as a way of converting the lateral crus to a flat, straight segment
      with resultant correction of the convexity. Since then, this suture technique has
      been employed in most primary and some secondary rhinoplasties and has stood the
      test of time. We report our experience with this technique, including a slight
      modification to facilitate its application when the cartilage is unusually narrow
      or when the original technique is difficult to complete. In addition, the suture
      technique for the less concave lateral crura is redescribed. It, too, has
      withstood the test of time.

PMID- 25568232
TI  - Superior rhinoplasty outcomes with precise nasal osteotomy: an individualized
      approach for maintaining function and achieving aesthetic goals.
AB  - BACKGROUND: Although frequently performed in rhinoplasty, nasal osteotomies have
      been unpredictable in consistently controlling postoperative alterations in bony
      morphology in many patients. Consequently, a detailed algorithm for an
      individualized approach to osteotomy is needed to achieve superior aesthetic and
      functional outcomes. OBJECTIVES: The authors aimed to propose a component
      oriented and individualized approach for nasal osteotomy in rhinoplasty. METHODS:
      Clinical outcomes were reviewed for 150 consecutive patients who underwent
      rhinoplasty. Type and frequency of specific osteotomy procedures and preoperative
      and postoperative photographs were examined. RESULTS: A total of 97 cases with at
      least 12 months of follow-up data were evaluated. In 92 of 97 patients (95%), a
      lateralized medial oblique osteotomy was performed; 70 (72%) required bilateral
      intermediate osteotomy, and 21 (22%) required unilateral osteotomy. Forty-one
      patients (42%) underwent bilateral base osteotomy and 24 (25%) underwent
      unilateral base osteotomy. No base osteotomy was performed in 32 patients (33%)
      who had aesthetically pleasing lateral wall width and no convexity of the
      posterior portion of the lateral bony wall. CONCLUSIONS: The osteocartilaginous
      vault is asymmetric in the majority of patients undergoing rhinoplasty. Anatomic
      variations in the height, length, and/or width of the bony vault can
      significantly influence its shape and symmetry. Various principles and techniques
      for nasal osteotomy increase predictability of outcomes while improving nasal
      aesthetics and function. LEVEL OF EVIDENCE 4: Therapeutic.

PMID- 25568233
TI  - Further evidence that human acellular dermal matrix decreases inflammatory
      markers of capsule formation in implant-based breast reconstruction.
AB  - BACKGROUND: Human acellular dermal matrix (HADM; previously termed "acellular
      cadaveric dermis") may limit inflammatory changes believed to play a role in
      capsular contracture, a common complication of implant-based breast
      reconstruction. OBJECTIVES: Differences between HADM and native breast capsule
      specimens were evaluated by immunohistochemical analysis of key inflammatory
      markers involved in capsule formation. METHODS: Twenty consecutive patients
      underwent immediate, 2-stage, implant-based breast reconstruction with dual-plane
      HADM. During tissue expander-implant exchange, full-thickness biopsies of
      biointegrated HADM and native breast capsule (internal control) from the tissue
      expander envelope were obtained. Immunohistochemical analysis was performed for
      endothelial cells (CD31), B cells (CD20), T cells (CD3), macrophages (CD68),
      collagen I and III, and myofibroblasts (alpha-smooth muscle actin). Observed
      levels of marker labeling were semiquantitatively scored from 0 (none) to 3
      (severe) by a blinded histopathologist and were statistically analyzed with the
      Wilcoxon rank sum test. RESULTS: A bilateral sample was obtained from 1 patient;
      all other samples were unilateral. Compared with capsule samples from native
      breast tissue, HADM samples had significantly lower levels of all inflammatory
      markers (P < .001). CONCLUSIONS: These lower levels of inflammatory markers
      support previous evidence that HADM may inhibit inflammatory and profibrotic
      signaling characteristics of breast capsule development and decrease the risk of
      capsular contracture. Further investigation is needed to determine the mechanism
      by which HADM inhibits these inflammatory cells, whether HADM reduces the
      incidence of breast capsular contracture, and if so, the longevity of this
      effect.

PMID- 25568234
TI  - Breast implants and the risk of breast cancer: a meta-analysis of cohort studies.
AB  - BACKGROUND: The popularity of cosmetic breast augmentation and the incidence of
      breast cancer have been increasing worldwide. It has been hypothesized that the
      risk of breast cancer may be greater among patients who have undergone cosmetic
      breast implantation. OBJECTIVES: The authors performed a meta-analysis of the
      available literature on the risk of breast cancer among women with cosmetic
      breast implants. METHODS: The study was designed as a meta-analysis of
      observational studies. A systematic search of the English literature (published
      by August 28, 2013) was conducted in PubMed and EMBASE. Eligible reports were
      those that included relative risk (RR; the increased or decreased risk of breast
      cancer associated with breast implants) or the standardized incidence ratio (SIR)
      of the observed number of cases of breast cancer to the expected number of cases
      among patients that previously underwent cosmetic breast augmentation. RESULTS:
      Seventeen studies representing 7 cohorts were selected. Some of these were follow
      up reports of previously published studies; in such cases, only the most recent
      reports were included in the meta-analysis. Summary SIR and RR rates and the
      corresponding 95% confidence intervals (CIs) were calculated with a random
      effects (SIR) or fixed-effects (RR) model. The overall SIR estimate was 0.69 (95%
      CI, 0.56-0.85), and the overall RR, based on 4 studies, was 0.63 (95% CI, 0.56
      0.71). CONCLUSIONS: Finding of this meta-analysis suggest that women who have
      undergone cosmetic breast implantation do not have an increased risk of breast
      cancer.

PMID- 25568235
TI  - Commentary on: Breast implants and the risk of breast cancer: a meta-analysis on
      cohort studies.

PMID- 25568236
TI  - Cryolipolysis conformable-surface applicator for nonsurgical fat reduction in
      lateral thighs.
AB  - BACKGROUND: Vacuum applicators have been effective for cryolipolysis of the
      abdomen, flanks, inner thighs, back, chest, and arms. However, the lateral thighs
      have not been easily treated because fat from this area cannot be easily drawn
      into a vacuum cup. OBJECTIVES: The authors investigated the safety and efficacy
      of a prototype applicator for treatment of "nonpinchable" fat in the lateral
      thighs. METHODS: In this prospective, nonrandomized, interventional cohort,
      multicenter study, a 120-minute unilateral treatment with a prototype conformable
      surface applicator was performed on 1 lateral thigh of 40 patients, with the
      contralateral thigh serving as the control. During follow-up visits at 2 and 4
      months, fat reduction was assessed by ultrasound imaging and clinical
      photography, and patient satisfaction surveys were completed. RESULTS: Ultrasound
      data indicated a 2.6-mm mean normalized reduction in fat thickness-a
      statistically significant reduction vs the untreated control thigh (P = 7.8E-8).
      According to patient survey responses, 89% of patients would recommend the
      procedure to a friend; 86% were satisfied with cryolipolysis for the lateral
      thighs; 86% noticed visible fat reduction; and 97% were likely to undergo a
      second treatment. A panel of 3 independent blinded physicians correctly
      identified baseline and posttreatment clinical photographs in 87% of cases. There
      were no serious adverse events or unanticipated adverse device effects.
      CONCLUSIONS: The cryolipolysis conformable-surface applicator was safe and
      efficacious for treatment of lateral thigh fat. Clinical photographs and
      ultrasound results showed significant reduction in fat thickness, and noticeable
      reduction in undesirable "saddlebag" bulges. LEVEL OF EVIDENCE 3: Therapeutic.

PMID- 25568237
TI  - The impact of perioperative hypothermia on plastic surgery outcomes: a
      multivariate logistic regression of 1062 cases.
AB  - BACKGROUND: Perioperative hypothermia has been associated with increased rates of
      infection, prolonged recovery time, and coagulopathy. OBJECTIVES: The authors
      assessed the impact of hypothermia on patient outcomes after plastic surgery and
      analyzed the impact of prewarming on postoperative outcomes. METHODS: The medical
      charts of 1062 patients who underwent complex plastic surgery typically lasting
      at least 1 hour were reviewed. Hypothermia was defined as a temperature at or
      below 36 degrees C. Postoperative complication data were collected for outcomes
      including infection, delayed wound healing, seroma, hematoma, dehiscence, deep
      venous thrombosis, and overall wound problems. Odds ratios (ORs) were estimated
      from 3 multivariate logistic regression models of hypothermia and one model of
      body contouring procedures that included prewarming as a parameter. RESULTS:
      Perioperative hypothermia was not a significant predictor of wound problems (OR =
      0.83; P = .28). In the stratified regression model, hypothermia did not
      significantly impact wound problems. The regression model measuring the
      interaction between hypothermia and operating time did not show a significantly
      increased risk of wound problems. Prewarming did not significantly affect
      perioperative hypothermia (P = .510), and in the model of body contouring
      procedures with prewarming as a categorical variable, massive weight loss was the
      most significant predictor of wound complications (OR = 2.57; P = .003).
      Prewarming did not significantly affect outcomes (OR = 1.49; P = .212).
      CONCLUSIONS: Based on univariate and multivariate models in our study, mild
      perioperative hypothermia appears to be independent of wound complications. LEVEL
      OF EVIDENCE 4: Risk.

PMID- 25568238
TI  - Commentary on: The impact of perioperative hypothermia on plastic surgery
      outcomes: a multivariate logistic regression of 1062 cases.

PMID- 25568239
TI  - A simple device for syringe-to-syringe transfer during lipofilling.

PMID- 25568240
TI  - Superior pedicle technique of reduction mammaplasty: a stepwise approach.
AB  - Numerous surgical options for breast reduction have been described, but in the
      current healthcare environment, efficiency is of the utmost importance. In this
      Featured Operative Technique, the authors describe an efficient, reproducible,
      and simple method for minimal to moderate reduction mammaplasty that utilizes a
      superior pedicle. The surgical maneuvers were developed and conveyed to the
      senior author (W.G.S.) by Dr John Bostwick. This approach preserves superior and
      medial breast fullness while providing appropriate resection of the breast
      parenchyma to ameliorate symptoms and produce a smaller, lifted breast with a
      more youthful appearance. The surgical technique maintains a reliable blood
      supply to the nipple-areola complex (NAC) from the internal mammary artery and
      its perforators, and involves minimal transposition of the NAC. The authors
      reviewed the charts of 62 consecutive patients who underwent this procedure and
      found the complication rate to be 11.3%. Complications included 1 hematoma, 1
      standing cone deformity, 3 soft-tissue infections, 8 incisional breakdowns, and 1
      unilateral necrosis of the NAC. 

PMID- 25568241
TI  - Introduction to the EBM Hub in the Aesthetic Surgery Journal.

PMID- 25568246
TI  - Thiamine deficiency: a cause of profound hypotension and hypothermia after
      plastic surgery.
AB  - A 72-year-old woman became profoundly hypotensive and hypothermic 10 hours after
      undergoing a panniculectomy. She remained critically ill despite aggressive
      intensive care, and a diagnosis was not identified despite multiple
      consultations, imaging, and exploratory laparatomy. No improvement was seen until
      a large dose of intravenous thiamine alone was administered, dramatically
      restoring a normotensive and normothermic state. Although few cases of thiamine
      deficiency have been described in the context of plastic and reconstructive
      surgery, this case emphasizes the importance of considering this potentially
      fatal condition, which often does not manifest classically in the early
      postoperative period.

PMID- 25568247
TI  - Is there a link between longer operating times and increased risk?

PMID- 25568248
TI  - Avoiding tension of wound closure in reduction mammaplasty and mastopexy in
      previously irradiated breasts.

PMID- 25568249
TI  - Response to "Avoiding tension of wound closure in reduction mammaplasty and
      mastopexy in previously irradiated breasts".

PMID- 25568250
TI  - Response to "Avoiding tension of wound closure in reduction mammaplasty and
      mastopexy in previously irradiated breasts".

PMID- 25568251
TI  - Commentary on: Thiamine deficiency: a cause of profound hypotension and
      hypothermia after plastic surgery.

PMID- 25568252
TI  - Papers regarding operative times and complications can be misleading.

PMID- 25568253
TI  - Response to: "Is there a link between longer operating times and increased risk?"
      and "Papers regarding operative times and complications can be misleading".

PMID- 25568258
TI  - Trainees can learn minimally invasive aortic valve replacement without
      compromising safety.
AB  - OBJECTIVES: Minimally invasive aortic valve replacement (Mini-AVR) is a
      technically advanced procedure. However, it results in equivalent operative
      mortality, less bleeding and reduced intensive care/hospital stay when compared
      with conventional AVR. Our aim was to assess the impact of trainee performance on
      short-term outcomes of patients undergoing elective and urgent Mini-AVR where a
      significant proportion were performed by trainees. METHODS: All patients
      undergoing non-emergency, elective and urgent, isolated Mini-AVR between
      September 2005 and December 2012 were studied. Operative details and short-term
      outcomes, with particular attention to trainee performance, were analysed.
      RESULTS: During the study period, there were 205 Mini-AVR with a median age of 67
      years (range 29-86); 74 (36%) operations were performed by trainees. The overall
      median cross-clamp and bypass times were 42 (range 33-63) and 59 min (range 59
      94) for the attending surgeon and 52 (range 42-63) and 71 min (range 59-94) for
      the trainee (P = 0.03). Five Mini-AVR patients (2.4%) required conversion to full
      sternotomy for ascending aortic replacement, right ventricular bleeding, coronary
      artery bypass graft surgery and failure to cardiovert. None of these cases were
      performed by trainees. Median lengths of intensive care and hospital stay were 1
      and 5 days and were not different for attending surgeon and trainee. Only 1
      (0.5%) patient died in hospital. CONCLUSIONS: Mini-AVR can be performed with a
      low conversion rate and hospital stay and taught to trainees without compromising
      safety.

PMID- 25568259
TI  - Pyomelanin production in Penicillium chrysogenum is stimulated by L-tyrosine.
AB  - From a tomb in Upper Egypt we isolated a strain of Penicillium chrysogenum that
      was capable of producing brown pigment in vitro when grown in a minimal salts
      medium containing tyrosine. We present evidence that this pigment is a
      pyomelanin, a compound that is known to assist in the survival of some micro
      organisms in adverse environments. We tested type strains of Pe. chrysogenum,
      which were also able to produce this pigment under similar conditions. Inhibitors
      of the DHN and DOPA melanin pathways were unable to inhibit the formation of the
      pigment. Fourier transform IR analysis indicated that this brown pigment is
      similar to pyomelanin. Pyrolysis-GC/MS revealed the presence of phenolic
      compounds. Using LC/MS, homogentisic acid, the monomeric precursor of pyomelanin,
      was detected in supernatants of Pe. chrysogenum cultures growing in tyrosine
      medium but not in cultures lacking tyrosine. Partial regions of the genes
      encoding two enzymes in the homogentisic acid pathway of tyrosine degradation
      were amplified. Data from reverse-transcription PCR demonstrated that hmgA
      transcription was increased in cultures grown in tyrosine medium, suggesting that
      tyrosine induced the transcription. 

PMID- 25568260
TI  - Cooperative regulation of the common target genes between H2O2-sensing YedVW and
      Cu2+-sensing CusSR in Escherichia coli.
AB  - YedVW is one of the uncharacterized two-component systems (TCSs) of Escherichia
      coli. In order to identify the regulation targets of YedVW, we performed genomic
      SELEX (systematic evolution of ligands by exponential enrichment) screening using
      phosphorylated YedW and an E. coli DNA library, and identified YedW-binding sites
      within three intergenic spacers, yedW-hiuH, cyoA-ampG and cusR-cusC, along the E.
      coli genome. Using a reporter assay system, we found that transcription of hiuH,
      encoding 5-hydroxyisourate hydrolase, was induced at high concentrations of
      either Cu(2+) or H2O2. Cu(2+)-dependent expression of hiuH was observed in the
      yedWV knockout mutant, but was reduced markedly in the cusRS-null mutant.
      However, H2O2-induced hiuH expression was observed in the cusRS-null mutant, but
      not in the yedWV-null mutant. Gel mobility shift and DNase I footprinting
      analyses showed binding of both YedW and CusR to essentially the same sequence
      within the hiuH promoter region. Taken together, we concluded that YedVW and
      CusSR formed a unique cooperative TCS pair by recognizing and regulating the same
      targets, but under different environmental conditions - YedVW played a role in
      H2O2 response regulation, whilst CusSR played a role in Cu(2+) response
      regulation.

PMID- 25568261
TI  - Christmas disease: diagnosis and management of a haemorrhagic diathesis following
      dentofacial trauma.
AB  - Haemorrhagic diathesis has been of much concern to health professionals including
      dentists. It is not infrequent that a dentist becomes the first person to
      diagnose a bleeding disorder while performing dental treatment. Haemophilia is an
      X linked disorder with a frequency of about 1:10,000 births. Haemophilia B is
      much less common than haemophilia A, and affects only 1:300,000 males born alive.
      The clinical features of haemophilia B are very similar to those of haemophilia A
      with a prolongation of activated partial thromboplastin time. This case report
      describes the dental management of a patient with an uncommon haematological
      disorder, namely, factor IX deficiency, which remained undiagnosed until the
      patient had to undergo dentofacial trauma with unexpected severe haemorrhage.
      Preventive dentistry remains vital to young haemophiliacs. Surgical dental
      procedures may be performed for haemophiliacs but they must be judiciously
      coordinated by dental and medical health professionals.

PMID- 25568262
TI  - A rare but potentially fatal cause of diarrhoea and weight loss: enteropathy
      associated T-cell lymphoma.
AB  - Enteropathy-associated T-cell lymphoma (EATL) is a rare but potentially fatal
      cause of diarrhoea and weight loss. EATL commonly presents with abdominal pain,
      diarrhoea and weight loss, but can also present with complications such as bowel
      obstruction and perforation. It is a tumour of intraepithelial lymphocytes that
      occurs in a relatively young population. It is the most common neoplastic
      complication of coeliac disease, but can occur with no prior diagnosis of coeliac
      disease. This case demonstrates the difficulties that can be faced in diagnosing
      this disorder, particularly when there is no preceding history of coeliac
      disease. Early diagnosis is of utmost importance in order to start treatment
      before the effects of malnutrition increase the risk of complications from
      chemotherapy. Hence awareness of the condition among general medical physicians,
      to whom it will often present first, is essential. However, even with prompt
      diagnosis, outcomes for this condition remain poor. 

PMID- 25568263
TI  - Obliteration of the medullary canal in an atypical bisphosphonate-related femoral
      fracture.
AB  - We present a case of a patient with a bisphosphonate-related atypical femoral
      fracture. Her surgical management was complicated by obliteration of the
      medullary canal, which prohibited the passage of an intramedullary nail. The
      relevant literature is discussed. 

PMID- 25568264
TI  - Borrelial pseudolymphoma of the nose.
AB  - A 52-year-old Colombian woman, a patient with psoriasis, undergoing phototherapy
      with (ultraviolet B narrowband) UVBnb, presented with a symptomless solitary
      diffuse erythaematous plaque on her nose for 3 months. Initially, she was treated
      with pimecrolimus 1% cream for 8 weeks, which was then combined with
      metronidazole cream for 4 weeks, with the initial diagnosis of UV-triggered
      rosacea, without improvement. A punch biopsy was performed and the histology
      showed a pseudolymphomatous reaction. The diagnosis of nasal pseudolymphoma of
      borreliosis was confirmed with PCR. The lesion completely resolved following oral
      doxycycline therapy. 

PMID- 25568265
TI  - Haematuria and loin pain, could this be tuberculosis?
AB  - We report a case of an 18-year-old Caucasian male presenting with haematuria and
      loin pain while working as a locksmith. He was systemically well with normal
      vital signs. Peripheral blood testing demonstrated renal failure, secondary to
      hydronephrosis, caused by haemorrhagic cystitis with no obvious cause for the
      obstruction. The patient was diagnosed with a urinary tract infection and treated
      with antibiotics. He responded well and his renal function improved. Four months
      later he re-presented with the above symptoms, weight loss and night sweats,
      bladder wall biopsy at this point confirmed tuberculosis. 

PMID- 25568266
TI  - Granulicatella adiacens subacute bacterial endocarditis as the underlying cause
      of type II mixed cryoglobulinaemia.
AB  - A 57-year-old man with type II mixed cryoglobulinaemia presented to the emergency
      department with a history of worsening lethargy, malaise and non-drenching night
      sweats in a relapsing-remitting pattern. He was diagnosed with type II mixed
      cryoglobulinaemia 7 months ago following episodes of fever, night sweats,
      lethargy and malaise associated with a non-blanching, purpuric, raised
      erythematous rash that responded partially to immunosuppressive therapy and short
      courses of oral antibiotics. A single blood culture then yielded Granulicatella
      adiacens which was reported as a possible contaminant and therefore, not pursued.
      Despite numerous other investigations, the underlying cause of his type II
      cryoglobulinaemia remained undetermined. On his current presentation, the
      physical examination revealed signs of infective endocarditis. Two further blood
      cultures grew G. adiacens. The diagnosis of infective endocarditis was
      established on a transoesophageal echocardiography, and the subsequent antibiotic
      and surgical therapy resulted in complete remission of his type II mixed
      cryoglobulinaemia. 

PMID- 25568267
TI  - Metastatic renal cell carcinoma mimicking diverticulitis in a patient with
      chronic lymphocytic leukaemia.
AB  - We present an unusual case of metastatic renal cell carcinoma (RCC) mimicking
      diverticulitis in a 76-year-old man with a 16-year history of chronic lymphocytic
      leukaemia (CLL) and a 2 cm left renal mass. The patient presented with severe
      abdominal pain and lower gastrointestinal bleeding with anticoagulation from
      recent pulmonary embolism. His clinical course was troubled by recurrent
      hospitalisations and complications that delayed investigations and potential
      treatments. Radiographic findings revealed stable CLL, mild sigmoid
      diverticulitis and a small renal mass. Small renal masses (less than 4 cm) are
      considered low risk for metastasising and are, thus, often observed or ablated,
      rather than resected. Furthermore, gastrointestinal metastases from RCC are rare.
      This case adds new perspective to the unpredictable nature of RCC and how
      synchronous malignancies may be masked in patients with long-standing CLL. 

PMID- 25568269
TI  - Cardiac arrest caused by a pacemaker check.

PMID- 25568268
TI  - The catastrophic journey of a retained temporary epicardial pacemaker wire
      leading to Enterococcus faecalis endocarditis and subsequent stroke.
AB  - A 52-year-old man underwent triple coronary artery bypass graft (CABG). Three
      months later, he presented to the emergency room with dizziness and left-sided
      weakness. Workup revealed right frontal parenchymal haemorrhage; also, two
      retained temporary epicardial pacemaker wires (TEPW) from his previous CABG were
      observed, one of which had significantly migrated. One wire was found in the soft
      tissues below the heart; the other transversed the mediastinum from the expected
      location of the right atrium, perforating the right atrial appendage, entering
      the lumen of the ascending aorta and coursing into the mid-descending aorta.
      There were vegetations (Enterococcus spp) on the migrated TEPW and aortic valve,
      aortic valve endocarditis and aortic regurgitation. In summary, we suspect the
      migrated TEPW may be the source of bacteria that seeded the aortic valve, causing
      endocarditis and contributing to the patient's subsequent stroke. Management
      involved two 6-week antibiotic courses, wire-extraction, aortic valve replacement
      and redo CABG. 

PMID- 25568270
TI  - Persistent unilateral central serous chorioretinopathy in a breastfeeding woman.
AB  - A 40-year-old woman presented with blurred vision and floaters in her right eye
      for the past 7 months. The patient was in the sixth month of pregnancy at onset
      of the ocular symptoms and had persistent ocular disturbances postpartum. Her
      medical and ocular history were unremarkable except for LASIK surgery.
      Examination revealed an uncorrected visual acuity of 20/30 and 20/20 in the right
      and left eye, respectively. Fundus examination showed a round, subretinal exudate
      involving the foveal centre. Central serous chorioretinopathy was diagnosed by
      fluorescein angiogram and optical coherence tomography (OCT) showing foveal
      neurosensory detachment and treated with intravitreal bevacizumab. At her 4-month
      follow-up (8 month postpartum), OCT continued to show persistent foveal
      subretinal fluid. Patient declined further treatment and on follow-up 1 year
      later, still showed a persistent neurosensory detachment on OCT testing. 

PMID- 25568271
TI  - Rare mutation in the SLC26A3 transporter causes life-long diarrhoea with
      metabolic alkalosis.
AB  - SLC26A3, a chloride/bicarbonate transporter mainly expressed in the intestines,
      plays a pivotal role in chloride absorption. We present a 23-year-old woman with
      a history of congenital chloride diarrhoea (CCD) and renal transplant who was
      admitted for rehydration and treatment of acute kidney injury after she presented
      with an acute diarrhoeal episode. Laboratory investigations confirmed metabolic
      alkalosis and severe hypochloraemia, consistent with her underlying CCD. This
      contrasts with most other forms of diarrhoea, which are normally associated with
      metabolic acidosis. Genetic testing was offered and revealed a homozygous non
      sense mutation in SLC26A3 (Gly-187-Stop). This loss-of-function mutation results
      in bicarbonate retention in the blood and chloride loss into the intestinal
      lumen. Symptomatic management with daily NaCl and KCl oral syrups was
      supplemented with omeprazole therapy. The loss of her own kidneys is most likely
      due to crystal-induced nephropathy secondary to chronic volume contraction and
      chloride depletion. This case summarises the pathophysiology and management of
      CCD. 

PMID- 25568272
TI  - Rickettsial infection caused by accidental conjunctival inoculation.
AB  - The most common transmission route of tick-borne Rickettsia is through tick bite;
      nevertheless, other transmission routes should also be considered. We report a
      case of rickettsial infection in a 15-year-old boy caused by accidental
      contamination of the conjunctiva through the infected fluid of a crushed engorged
      tick removed from a dog. Right eye pain, conjunctival hyperaemia with
      mucopurulent exudate, chemosis and eyelid oedema were the first signs and
      symptoms. Two days later, the boy developed fever, myalgia, headache, abdominal
      pain and was vomiting; physical examination showed multiple cervical adenopathies
      but no rash. He was treated with doxycycline (200 mg/day) for 7 days with
      progressive resolution of clinical signs. Rickettsial infection was confirmed by
      immunofluorescence assay with serological seroconversion in two consecutive
      samples. Rickettsia conorii or Rickettsia massiliae were the possible causal
      agents since they are the Rickettsia spp found in the Rhipicephalus sanguineus
      dog tick in Portugal. 

PMID- 25568273
TI  - The dilemma of evaluating a continuous murmur in a patient of aneurysm of sinus
      of Valsalva and coronary cameral fistula presenting with supraventricular
      tachycardia.
AB  - A 39-year-old hypothyroid woman on thyroxine replacement therapy presented with
      an unresolving episode of palpitations (narrow-complex tachycardia). Clinical
      examination, after reversion to normal sinus rhythm revealed a precordial
      continuous murmur. Initial transthoracic echocardiogram showed an unruptured
      aneurysm of left sinus of Valsalva (LSOV), however, because a continuous murmur
      could not be explained by this condition, a repeat colour Doppler study was made,
      revealing a communicating tract from the left main coronary artery (LMCA) and
      terminating in the right atrium (RA). A transesophageal echocardiogram revealed
      an aneurysmal LMCA and LSOV, with similar colour Doppler findings. A further CT
      scan and coronary angiogram confirmed a coronary cameral fistula opening into RA.
      In conclusion, the relevance of a diligent clinical examination and imaging after
      conversion to normal sinus rhythm in picking up such anomalies cannot be over
      emphasised, as previous routine echocardiograms on the same patient had been
      reported as normal. 

PMID- 25568274
TI  - Follicular cell dendritic sarcoma of cervical nodes in a patient with significant
      WTC exposure.
AB  - A patient who worked at the World Trade Center (WTC) site presented with right
      cervical lymphadenopathy. He underwent right neck dissection. The final pathology
      showed follicular dendritic cell sarcoma. He was treated with radiation and
      chemotherapy and remained free of disease initially. He then presented with left
      cervical lymphadenopathy 2.5 years later and underwent a left neck dissection
      with similar pathology. A discussion of the disease process and WTC exposure is
      presented. Clinicians should be cognisant of this disease process and the latency
      between WTC exposure and the onset of sarcomas. 

PMID- 25568275
TI  - Swinging cardiac calcified amorphous tumour arising from a calcified mitral
      annulus in a patient with normal renal function.
AB  - A 67-year-old man was referred to our institution for the management of a left
      sided intracardiac mass discovered following two cardioembolic events. Imaging
      studies revealed a highly mobile mass attached to the ventricular side of a
      calcified mitral annulus. The mass had not been present on echocardiography 1
      year earlier. Surgical resection was performed. Microscopic examination confirmed
      the diagnosis of a calcified amorphous tumour. The postoperative course was
      unremarkable, and the patient remains asymptomatic and without recurrence of a
      mass or neurological event after a 12-month follow-up. 

PMID- 25568276
TI  - Percutaneous breast implant herniation: a rare complication of miliary TB.
AB  - We describe the case of a 46-year-old female patient treated for disseminated
      tuberculosis (TB) infection involving the lungs, urinary tract and skin.
      Following initiation of antituberculous therapy, the patient's right breast
      implant eroded through the overlying skin and was seen to be herniating through
      the resulting defect. The breast implant was removed under local anaesthetic and
      histological analysis of the resected tissue demonstrated granuloma formation
      consistent with periprosthetic TB. Wound healing following implant removal was
      poor and future breast augmentation surgery was only considered following
      completion of 12 months anti-TB treatment. This case constitutes the first report
      in the literature of percutaneous breast implant herniation resulting from
      periprosthetic infection with TB. A high index of suspicion is required to ensure
      early detection and timely management of TB and, in cases where periprosthetic
      pus aspirate is sterile, mycobacterial infection must be actively excluded. 

PMID- 25568277
TI  - Subungual squamous cell carcinoma.
AB  - Subungual squamous cell carcinoma (SCC) is rare. We present a case of subungual
      SCC with invasion into the underlying bone and review the literature. 

PMID- 25568278
TI  - Air Duster abuse causing rapid airway compromise.
AB  - Inhalant abuse is potentially life-threatening and has resulted in many
      complications such as central nervous system depression, cardiac dysrhythmia and
      hypoxia. Inhalant abuse causing angioedema is rarely reported in the medical
      literature. In this report we present a case of rapidly progressive airway
      compromise following recreational huffing. Our patient required intubation and
      intensive care unit admission with complete recovery after 5 days. The aetiology
      of airway compromise is postulated to be due to commonly reported frost bite
      injury and rarely reported angioedema. To the best of our knowledge this the
      second case reporting angioedema secondary to huffing Air Duster. 

PMID- 25568279
TI  - GlycoMine: a machine learning-based approach for predicting N-, C- and O-linked
      glycosylation in the human proteome.
AB  - MOTIVATION: Glycosylation is a ubiquitous type of protein post-translational
      modification (PTM) in eukaryotic cells, which plays vital roles in various
      biological processes (BPs) such as cellular communication, ligand recognition and
      subcellular recognition. It is estimated that >50% of the entire human proteome
      is glycosylated. However, it is still a significant challenge to identify
      glycosylation sites, which requires expensive/laborious experimental research.
      Thus, bioinformatics approaches that can predict the glycan occupancy at specific
      sequons in protein sequences would be useful for understanding and utilizing this
      important PTM. RESULTS: In this study, we present a novel bioinformatics tool
      called GlycoMine, which is a comprehensive tool for the systematic in silico
      identification of C-linked, N-linked, and O-linked glycosylation sites in the
      human proteome. GlycoMine was developed using the random forest algorithm and
      evaluated based on a well-prepared up-to-date benchmark dataset that encompasses
      all three types of glycosylation sites, which was curated from multiple public
      resources. Heterogeneous sequences and functional features were derived from
      various sources, and subjected to further two-step feature selection to
      characterize a condensed subset of optimal features that contributed most to the
      type-specific prediction of glycosylation sites. Five-fold cross-validation and
      independent tests show that this approach significantly improved the prediction
      performance compared with four existing prediction tools: NetNGlyc, NetOGlyc,
      EnsembleGly and GPP. We demonstrated that this tool could identify candidate
      glycosylation sites in case study proteins and applied it to identify many high
      confidence glycosylation target proteins by screening the entire human proteome.
      AVAILABILITY AND IMPLEMENTATION: The webserver, Java Applet, user instructions,
      datasets, and predicted glycosylation sites in the human proteome are freely
      available at http://www.structbioinfor.org/Lab/GlycoMine/. CONTACT:
      Jiangning.Song@monash.edu or James.Whisstock@monash.edu or
      zhangyang@nwsuaf.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25568280
TI  - The anisotropic network model web server at 2015 (ANM 2.0).
AB  - SUMMARY: The anisotropic network model (ANM) is one of the simplest yet powerful
      tools for exploring protein dynamics. Its main utility is to predict and
      visualize the collective motions of large complexes and assemblies near their
      equilibrium structures. The ANM server, introduced by us in 2006 helped making
      this tool more accessible to non-sophisticated users. We now provide a new
      version (ANM 2.0), which allows inclusion of nucleic acids and ligands in the
      network model and thus enables the investigation of the collective motions of
      protein-DNA/RNA and -ligand systems. The new version offers the flexibility of
      defining the system nodes and the interaction types and cutoffs. It also includes
      extensive improvements in hardware, software and graphical interfaces.
      AVAILABILITY AND IMPLEMENTATION: ANM 2.0 is available at http://anm.csb.pitt.edu
      CONTACT: eran.eyal@sheba.health.gov.il, eyal.eran@gmail.com.

PMID- 25568281
TI  - Selection of models for the analysis of risk-factor trees: leveraging biological
      knowledge to mine large sets of risk factors with application to microbiome data.
AB  - MOTIVATION: Establishment of a statistical association between microbiome
      features and clinical outcomes is of growing interest because of the potential
      for yielding insights into biological mechanisms and pathogenesis. Extracting
      microbiome features that are relevant for a disease is challenging and existing
      variable selection methods are limited due to large number of risk factor
      variables from microbiome sequence data and their complex biological structure.
      RESULTS: We propose a tree-based scanning method, Selection of Models for the
      Analysis of Risk factor Trees (referred to as SMART-scan), for identifying
      taxonomic groups that are associated with a disease or trait. SMART-scan is a
      model selection technique that uses a predefined taxonomy to organize the large
      pool of possible predictors into optimized groups, and hierarchically searches
      and determines variable groups for association test. We investigate the
      statistical properties of SMART-scan through simulations, in comparison to a
      regular single-variable analysis and three commonly-used variable selection
      methods, stepwise regression, least absolute shrinkage and selection operator
      (LASSO) and classification and regression tree (CART). When there are taxonomic
      group effects in the data, SMART-scan can significantly increase power by using
      bacterial taxonomic information to split large numbers of variables into groups.
      Through an application to microbiome data from a vervet monkey diet experiment,
      we demonstrate that SMART-scan can identify important phenotype-associated
      taxonomic features missed by single-variable analysis, stepwise regression, LASSO
      and CART.

PMID- 25568283
TI  - Clonality inference in multiple tumor samples using phylogeny.
AB  - MOTIVATION: Intra-tumor heterogeneity presents itself through the evolution of
      subclones during cancer progression. Although recent research suggests that this
      heterogeneity has clinical implications, in silico determination of the clonal
      subpopulations remains a challenge. RESULTS: We address this problem through a
      novel combinatorial method, named clonality inference in tumors using phylogeny
      (CITUP), that infers clonal populations and their frequencies while satisfying
      phylogenetic constraints and is able to exploit data from multiple samples. Using
      simulated datasets and deep sequencing data from two cancer studies, we show that
      CITUP predicts clonal frequencies and the underlying phylogeny with high
      accuracy. AVAILABILITY AND IMPLEMENTATION: CITUP is freely available at:
      http://sourceforge.net/projects/citup/. CONTACT: cenk@sfu.ca SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 25568282
TI  - A haplotype-based framework for group-wise transmission/disequilibrium tests for
      rare variant association analysis.
AB  - MOTIVATION: A major focus of current sequencing studies for human genetics is to
      identify rare variants associated with complex diseases. Aside from reduced power
      of detecting associated rare variants, controlling for population stratification
      is particularly challenging for rare variants. Transmission/disequilibrium tests
      (TDT) based on family designs are robust to population stratification and
      admixture, and therefore provide an effective approach to rare variant
      association studies to eliminate spurious associations. To increase power of rare
      variant association analysis, gene-based collapsing methods become standard
      approaches for analyzing rare variants. Existing methods that extend this
      strategy to rare variants in families usually combine TDT statistics at
      individual variants and therefore lack the flexibility of incorporating other
      genetic models. RESULTS: In this study, we describe a haplotype-based framework
      for group-wise TDT (gTDT) that is flexible to encompass a variety of genetic
      models such as additive, dominant and compound heterozygous (CH) (i.e. recessive)
      models as well as other complex interactions. Unlike existing methods, gTDT
      constructs haplotypes by transmission when possible and inherently takes into
      account the linkage disequilibrium among variants. Through extensive simulations
      we showed that type I error was correctly controlled for rare variants under all
      models investigated, and this remained true in the presence of population
      stratification. Under a variety of genetic models, gTDT showed increased power
      compared with the single marker TDT. Application of gTDT to an autism exome
      sequencing data of 118 trios identified potentially interesting candidate genes
      with CH rare variants. AVAILABILITY AND IMPLEMENTATION: We implemented gTDT in
      C++ and the source code and the detailed usage are available on the authors'
      website (https://medschool.vanderbilt.edu/cgg). CONTACT:
      bingshan.li@vanderbilt.edu or wei.chen@chp.edu SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 25568284
TI  - Disproportionate Reduction of Serotonin Transporter May Predict the Response and
      Adherence to Antidepressants in Patients with Major Depressive Disorder: A
      Positron Emission Tomography Study with 4-[18F]-ADAM.
AB  - BACKGROUND: Many lines of evidence suggest the role of serotonin transporter
      (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of
      major depressive disorder (MDD). This study aimed to examine whether the
      pretreatment of SERT binding potential or SERT binding ratio between terminal
      projection regions relative to the midbrain raphe nuclei was associated with
      treatment outcomes to SERT-targeted antidepressants. METHODS: We recruited 39
      antidepressant-naive patients with MDD and 39 heathy controls. Positron emission
      tomography with N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4
      [(18)F]-ADAM) was used to measure in vivo SERT availability prior to
      antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was
      use to assess the severity of depression from baseline to week 6. All the
      patients with MDD had HDRS scores of 18 or more. RESULTS: Pretreatment SERT
      binding in the thalamus and striatum positively correlated with an early
      reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a
      proportionate reduction in SERT binding in the terminal projection regions and
      midbrain compared to healthy controls. In contrast, a disproportionate reduction
      in SERT binding in the terminal projection regions relative to midbrain was
      observed in responders. CONCLUSIONS: The results of this study suggested that a
      disproportionate reduction in SERT binding between terminal projection regions
      and midbrain may predict better treatment outcomes in patients with MDD.

PMID- 25568285
TI  - Embryonic alcohol exposure impairs the dopaminergic system and social behavioral
      responses in adult zebrafish.
AB  - BACKGROUND: The zebrafish is a powerful neurobehavioral genetics tool with which
      complex human brain disorders including alcohol abuse and fetal alcohol spectrum
      disorders may be modeled and investigated. Zebrafish innately form social groups
      called shoals. Previously, it has been demonstrated that a single bath exposure
      (24 hours postfertilization) to low doses of alcohol (0, 0.25, 0.50, 0.75, and 1%
      vol/vol) for a short duration (2 hours) leads to impaired group forming, or
      shoaling, in adult zebrafish. METHODS: In the current study, we immersed
      zebrafish eggs in a low concentration of alcohol (0.5% or 1% vol/vol) for 2 hours
      at 24 hours postfertilization and let the fish grow and reach adulthood. In
      addition to quantifying the behavioral response of the adult fish to an animated
      shoal, we also measured the amount of dopamine and its metabolite 3,4
      dihydroxyphenylacetic acid from whole brain extracts of these fish using high
      pressure liquid chromatograph. RESULTS: Here we confirm that embryonic alcohol
      exposure makes adult zebrafish increase their distance from the shoal stimulus in
      a dose-dependent manner. We also show that the shoal stimulus increases the
      amount of dopamine and 3,4-dihydroxyphenylacetic acid in the brain of control
      zebrafish but not in fish previously exposed to alcohol during their embryonic
      development. CONCLUSIONS: We speculate that one of the mechanisms that may
      explain the embryonic alcohol-induced impaired shoaling response in zebrafish is
      dysfunction of reward mechanisms subserved by the dopaminergic system.

PMID- 25568288
TI  - Excessive fatal injury among migrant children in China: inequities in safety.
AB  - The wide variability in economic development levels among different regions in
      China results in the migration of millions of households to more developed areas.
      Death records from 2008 to 2012 of children aged 0-17 years old from the vital
      surveillance system of Guangzhou were used to determine if death rates were
      different for resident and migrant children. A total of 1358 injury-related
      deaths were identified with rates rising slightly from 2008 to 2012 both in
      resident and migrant populations. The total crude incidence rate of injury death
      was significantly higher among migrant households (29.50/100 000) compared with
      resident households (8.42/100 000). The adjusted rate in migrant households was
      3.50 (95% CI 3.14 to 3.89) times higher than in resident households. Drowning and
      traffic crashes represented the most common causes of death and residences were
      the most frequent site of injury-related death for both groups of children.
      Migrant children were at a significantly higher risk of injury-related mortality
      compared with local resident children. 

PMID- 25568287
TI  - Regional differences in brain-derived neurotrophic factor levels and dendritic
      spine density confer resilience to inescapable stress.
AB  - BACKGROUND: In the learned helplessness (LH) paradigm, approximately 35% of rats
      are resilient to inescapable stress. METHODS: The roles of brain-derived
      neurotrophic factor (BDNF) and dendritic spine density in the brain regions of LH
      (susceptible) and non-LH rats (resilient) were examined. Western blot analysis
      and Golgi staining were performed. RESULTS: BDNF levels in the medial prefrontal
      cortex, CA3, and dentate gyrus (DG) were significantly lower in the LH group than
      in the control and non-LH groups, whereas BDNF levels in the nucleus accumbens
      (NAc) in the LH group but not the non-LH group were significantly higher than
      those in the control group. Furthermore, spine density in the prelimbic cortex,
      CA3, and DG was significantly lower in the LH group than in the control and non
      LH groups, although spine density in the NAc was significantly higher in the LH
      group than in the control and non-LH groups. CONCLUSIONS: The results suggest
      that regional differences in BDNF levels and spine density in rat brain may
      contribute to resilience to inescapable stress.

PMID- 25568290
TI  - More evidence against alcohol or smoking in patients with unruptured intracranial
      aneurysm.

PMID- 25568289
TI  - Does teaching children to swim increase exposure to water or risk-taking when in
      the water? Emerging evidence from Bangladesh.
AB  - BACKGROUND: SwimSafe, a basic swimming and safe rescue curriculum, has been
      taught to large numbers of children in Bangladesh. Teaching swimming potentially
      increases risk if it increases water exposure or high-risk practices in water.
      This study compares water exposure and risk practices for SwimSafe graduates (SS)
      with children who learned swimming naturally. METHODS: Interviewers obtained
      detailed water exposure histories for the preceding 48 h from 3936 SS aged 6-14
      and 3952 age-matched and sex-matched children who had learned swimming naturally.
      Frequencies of water exposure and water entries for swimming or playing were
      compared. RESULTS: There were 9741 entries into water among the 7046 participants
      in the 48 h prior to interview. About one-third (31.2%) had no water entries, one
      tenth (10.5%) entered once, half (49.2%) entered twice and a tenth (9.1%) entered
      three or more times. Proportions of children in each group were similar. About
      99.5% of both groups only entered the water for bathing. For those entering to
      swim or play, the mean number of entries was similar (SS 1.63, natural swimmer
      (NS) 1.36, p=0.40). Swimming or playing alone in the water was rare (1 SS, 0 NS).
      CONCLUSIONS: Most water exposure for children is for bathing. Less than 1% swam
      or played in the water during the 48 h recall period (0.6% SS, 0.4% NS). Learning
      swimming in SwimSafe did not increase water exposure nor did it increase water
      entry for playing or swimming compared with children who learned to swim
      naturally.

PMID- 25568286
TI  - Isolation Housing Exacerbates Alzheimer's Disease-Like Pathophysiology in Aged
      APP/PS1 Mice.
AB  - BACKGROUND: Alzheimer's disease is a neurodegenerative disease characterized by
      gradual declines in social, cognitive, and emotional functions, leading to a loss
      of expected social behavior. Social isolation has been shown to have adverse
      effects on individual development and growth as well as health and aging.
      Previous experiments have shown that social isolation causes an early onset of
      Alzheimer's disease-like phenotypes in young APP695/PS1-dE9 transgenic mice.
      However, the interactions between social isolation and Alzheimer's disease still
      remain unknown. METHODS: Seventeen-month-old male APP695/PS1-dE9 transgenic mice
      were either singly housed or continued group housing for 3 months. Then,
      Alzheimer's disease-like pathophysiological changes were evaluated by using
      behavioral, biochemical, and pathological analyses. RESULTS: Isolation housing
      further promoted cognitive dysfunction and Abeta plaque accumulation in the
      hippocampus of aged APP695/PS1-dE9 transgenic mice, associated with increased
      gamma-secretase and decreased neprilysin expression. Furthermore, exacerbated
      hippocampal atrophy, synapse and myelin associated protein loss, and glial
      neuroinflammatory reactions were observed in the hippocampus of isolated aged
      APP695/PS1-dE9 transgenic mice. CONCLUSIONS: The results demonstrate that social
      isolation exacerbates Alzheimer's disease-like pathophysiology in aged APP695/PS1
      dE9 transgenic mice, highlighting the potential role of group life for delaying
      or counteracting the Alzheimer's disease process.

PMID- 25568291
TI  - Risk factors for all-cause death after diagnosis of unruptured intracranial
      aneurysms.
AB  - OBJECTIVES: We investigated all-cause mortality and risk factors of death of
      patients with unruptured intracranial aneurysms (UIAs) in a long-term follow-up
      study. METHODS: A total of 142 patients with 181 UIAs diagnosed between 1956 and
      1978 when UIAs were not treated were included in this study. Patients were
      followed until death or until 2011 to 2012. Mortality rates and risk factors were
      studied with Kaplan-Meier survival analysis and the Cox proportional hazards
      regression models. RESULTS: During 3,530 person-years, 113 (80%) had died, giving
      an average annual mortality of 3.2%. Of them, 19 (17%) died of aneurysm rupture
      from the index UIA, 6 (5%) of other aneurysm-related causes, and 2 (2%) of
      unspecified subarachnoid hemorrhage. The remaining 86 died of causes unrelated to
      intracranial aneurysms. The cumulative death rate was 20% (95% confidence
      interval 14%-27%) at 10 years and 60% (52%-68%) at 30 years. Independent risk
      factors for subsequent death were patient age (adjusted hazard ratio 1.09 per
      year, 95% confidence interval 1.05-1.12, p < 0.001), male sex (2.81, 1.59-4.96, p
      < 0.001), heavy alcohol use (4.22, 2.22-8.02, p < 0.001), and cigarette smoking
      (1.72, 0.97-3.07, p = 0.064). History of hypertension, family history of
      subarachnoid hemorrhage, and diameter of UIA predicted death only in univariable
      analysis. CONCLUSIONS: In patients of working age with a UIA, alcohol consumption
      and cigarette smoking are modifiable risk factors for untimely death through
      several causes and should be taken into account when treatment is considered.

PMID- 25568292
TI  - Recessive truncating IGHMBP2 mutations presenting as axonal sensorimotor
      neuropathy.
AB  - OBJECTIVE: To identify the cause of sensorimotor neuropathy in a cohort of
      patients with genetically unsolved neuropathies (57 families with a total of 74
      members) in whom hitherto known disease genes had been excluded. METHODS: We used
      autozygosity mapping or haplotype analysis to delineate potential disease loci in
      informative families. For mutation detection, we used either whole-exome
      sequencing or Sanger sequencing of positional candidates. Subsequently, a larger
      cohort was specifically screened for IGHMBP2 mutations. The pathogenicity of a
      splice-site mutation was verified in cultured patient skin fibroblasts on the
      messenger RNA level and by Western blot. RESULTS: We report on 5 patients with
      neuropathy from 3 families who carried truncating mutations in IGHMBP2. Contrary
      to the "classic" phenotype, they did not manifest with respiratory distress, but
      with progressive sensorimotor neuropathy. Only one patient required nocturnal
      mask ventilation, while 4 others maintained normal respiratory function by the
      age of 14, 18, 22, and 37 years. Three patients were still able to walk
      independently. All patients had a predominantly axonal sensorimotor neuropathy
      with subsequent muscle atrophy, but without obvious sensory symptoms. Two
      patients had signs of autonomic neuropathy. CONCLUSIONS: Mutations in IGHMBP2
      should be considered in the molecular genetic workup of patients with hereditary
      sensorimotor neuropathies, even in the absence of respiratory symptoms.

PMID- 25568293
TI  - Chipping away at the channels: Can we fashion a syndrome?

PMID- 25568294
TI  - Differential trigeminal myelinated and unmyelinated nerve fiber involvement in
      FOSMN syndrome.

PMID- 25568295
TI  - Age dependence of brain beta-amyloid deposition in Down syndrome: An
      [18F]florbetaben PET study.
AB  - OBJECTIVE: To investigate brain beta-amyloid binding in subjects with Down
      syndrome (DS) using [(18)F]florbetaben PET imaging. METHODS: Thirty-nine subjects
      with DS (46.3 +/- 4.7 years) were assessed with [(18)F]florbetaben PET imaging.
      Three blinded independent readers assessed the scans to provide a visual
      analysis. The primary quantitative imaging outcome was a standardized uptake
      value ratio (SUVR) obtained for 6 brain regions. Cognitive status was evaluated
      using the Dementia Screening Questionnaire for Individuals with Intellectual
      Disabilities (DSQIID). RESULTS: [(18)F]Florbetaben uptake was correlated with age
      (p < 0.0001, R(2) = 0.39); 90% of scans in subjects with DS aged 50 years or
      older (SUVR = 1.62 +/- 0.26), 53% in those aged 45 to 49 years (SUVR = 1.43 +/-
      0.16), and 7% in those aged 40 to 45 years (SUVR = 1.27 +/- 0.11) were visually
      assessed as positive. Visual and quantitative assessments were highly related
      (chi(2) = 11.3823, p = 0.0007; Cohen kappa = 0.58). Only 2 of 34 participants
      were considered to have dementia by the DSQIID. CONCLUSIONS: Brain beta-amyloid
      binding, as measured by [(18)F]florbetaben, increases with age in DS. Subjects
      with DS who have no evidence of dementia demonstrate brain beta-amyloid binding
      in vivo, suggesting that [(18)F]florbetaben PET imaging may detect beta-amyloid
      in this at-risk population.

PMID- 25568296
TI  - Lipid and lipoprotein measurements and the risk of ischemic vascular events:
      Framingham Study.
AB  - OBJECTIVES: To examine the relationship between plasma lipid measurements and
      incident ischemic vascular events (ischemic stroke [IS], and as a positive
      control, myocardial infarction [MI]) in a community cohort. METHODS: In 6,276
      stroke-free Framingham participants (aged 64 +/- 10 years, 56% female), we
      related plasma lipid levels (total cholesterol [TC], high-density lipoprotein
      cholesterol [HDL-C], and TC/HDL-C ratio) measured at the original cohort 15th
      (1977-1979) and 20th examination cycles (1986-1990) and (TC, HDL-C, TC/HDL-C
      ratio, triglycerides [TG], and low-density lipoprotein cholesterol [LDL-C])
      measured at the offspring fourth examination (1995-1998), to 10-year risk of
      incident IS and MI. Utilizing genome-wide genotyping in the same subjects, we
      used mendelian randomization methods to assess whether observed associations were
      incidental or causal. RESULTS: During a mean follow-up of 9 years, 301
      participants experienced incident IS. In multivariable-adjusted analyses, HDL-C
      <=40 mg/dL and TC/HDL ratio >=5 were associated with increased risk of IS (hazard
      ratio [95% confidence interval]: 1.59 [1.23-2.05], p < 0.001 and 1.47 [1.15
      1.87], p < 0.001), but not TC or LDL-C. In adjusted analysis, a strong
      association between TG and IS was diminished. In the MI-free sample (n = 5,875,
      aged 64 +/- 10 years, 58% female; 403 MI events), all lipid markers were
      associated with MI risk. A genetic risk score comprising 47 known determinants of
      circulating HDL-C was not associated with IS. CONCLUSIONS: In a middle-aged to
      elderly community sample, we observed that low HDL-C and high TC/HDL-C ratio, but
      not LDL-C or TG were associated with risk of incident IS. We observed the usual
      associations between lipids and risk of MI. Our findings suggest an important,
      but less likely causal, role of HDL-C over other lipid biomarkers for optimal
      stroke risk stratification.

PMID- 25568298
TI  - Reduced striatal dopamine transmission in REM sleep behavior disorder comorbid
      with depression.
AB  - OBJECTIVE: To investigate dopamine transmission in patients with comorbid REM
      sleep behavior disorder (RBD) and major depressive disorder (MDD). METHODS: This
      is a case-control study including 11 medicated patients with comorbid RBD and MDD
      (mean age 47.5 +/- 8.2), 8 medicated patients with MDD only (mean age 47.9 +/-
      8.4), and 10 healthy participants (mean age 46.5 +/- 10.6 years). They underwent
      clinical assessment, video-polysomnography, olfactory tests, and neuroimaging
      studies ((18)F-DOPA, (11)C-raclopride, and (18)F-FDG PET neuroimaging). RESULTS:
      Compared with the 2 control groups, patients with comorbid RBD and MDD had
      significantly lower (18)F-DOPA uptake at 60 minutes in the putamen and caudate
      after controlling for age and sex effect (p < 0.05). There were no significant
      differences for the (11)C-raclopride and (18)F-FDG-PET. The (18)F-DOPA uptake in
      putamens had significant inverse correlation with severity of RBD symptoms (p <
      0.01) and REM-related tonic muscle activity (p < 0.01). The comorbid RBD and MDD
      group had more impairment in olfactory function. CONCLUSION: Patients with
      comorbid RBD and MDD had presynaptic dopamine dysfunction and impaired olfactory
      function. There is a distinct possibility that the development of RBD symptoms
      among patients with MDD may represent an early phase of alpha-synucleinopathy
      neurodegeneration instead of a merely antidepressant-induced condition.

PMID- 25568297
TI  - Triheptanoin improves brain energy metabolism in patients with Huntington
      disease.
AB  - OBJECTIVE: Based on our previous work in Huntington disease (HD) showing improved
      energy metabolism in muscle by providing substrates to the Krebs cycle, we wished
      to obtain a proof-of-concept of the therapeutic benefit of triheptanoin using a
      functional biomarker of brain energy metabolism validated in HD. METHODS: We
      performed an open-label study using (31)P brain magnetic resonance spectroscopy
      (MRS) to measure the levels of phosphocreatine (PCr) and inorganic phosphate (Pi)
      before (rest), during (activation), and after (recovery) a visual stimulus. We
      performed (31)P brain MRS in 10 patients at an early stage of HD and 13 controls.
      Patients with HD were then treated for 1 month with triheptanoin after which they
      returned for follow-up including (31)P brain MRS scan. RESULTS: At baseline, we
      confirmed an increase in Pi/PCr ratio during brain activation in controls
      reflecting increased adenosine triphosphate synthesis-followed by a return to
      baseline levels during recovery (p = 0.013). In patients with HD, we validated
      the existence of an abnormal brain energy profile as previously reported. After 1
      month, this profile remained abnormal in patients with HD who did not receive
      treatment. Conversely, the MRS profile was improved in patients with HD treated
      with triheptanoin for 1 month with the restoration of an increased Pi/PCr ratio
      during visual stimulation (p = 0.005). CONCLUSION: This study suggests that
      triheptanoin is able to correct the bioenergetic profile in the brain of patients
      with HD at an early stage of the disease. CLASSIFICATION OF EVIDENCE: This study
      provides Class III evidence that, for patients with HD, treatment with
      triheptanoin for 1 month restores an increased MRS Pi/PCr ratio during visual
      stimulation.

PMID- 25568299
TI  - Urologic and gastrointestinal symptoms in the dystroglycanopathies.
AB  - OBJECTIVE: To determine the frequency of urologic and gastrointestinal (GI)
      symptoms in a cohort of individuals with dystroglycanopathy compared with healthy
      household controls. METHODS: Participants in a North American dystroglycanopathy
      natural history study (NCT00313677) and other members of their households
      completed a questionnaire modified from validated instruments and clinical
      criteria. Urologic and GI symptom frequency, effect on patient life, and
      medications taken for these symptoms were assessed. Those younger than 4 years or
      not toilet trained were excluded. Healthy human bladder, esophagus, and duodenum
      from surgical specimens were immunostained for glycosylated alpha-dystroglycan.
      RESULTS: Thirty of 58 potential participants with dystroglycanopathy (51.7%) and
      16 household controls participated. Subjects were aged 6 to 51 years (mean 26.7);
      60.0% were female. Controls were aged 7 to 55 years (mean 34.6); 56.3% were
      female. The dystroglycanopathy cohort had higher frequency of urinary voiding
      symptoms (p = 0.02), higher urologic symptom scores (p = 0.05), and higher
      dysphagia symptom scores (p = 0.04). A correlation existed between urologic
      symptom score and effect on life (r = 0.71; 95% confidence interval 0.46, 0.85; p
      < 0.0001) and between dysphagia symptom score and effect on life (r = 0.72; 95%
      confidence interval 0.48, 0.86; p < 0.0001). Glycosylated alpha-dystroglycan was
      present in visceral smooth muscle of all normal tissues analyzed. CONCLUSIONS:
      Urologic symptoms and dysphagia are reported more frequently by individuals with
      dystroglycanopathies than by household controls. These symptoms can cause a
      perceived negative effect on patient life. Our results suggest urologic and GI
      dysfunction may be part of the dystroglycanopathy phenotype, and that questions
      about these symptoms should be incorporated into routine care because they may
      influence medical management.

PMID- 25568302
TI  - Analysis of IL-22 contribution to hepcidin induction and hypoferremia during the
      response to LPS in vivo.
AB  - The anaemia of chronic disease (ACD) results from inflammation-mediated up
      regulation of the iron regulatory hormone hepcidin, with the consequent
      sequestration of iron limiting its availability for erythropoiesis. The
      inflammatory cytokine IL-6, a regulator of hepcidin, has been implicated in this
      process. Recent in vivo and in vitro studies indicate that IL-22 is also able to
      stimulate hepcidin expression. We aimed to determine if IL-22 had a role in
      causing the hypoferremia associated with the inflammatory response. Wild-type and
      Il22-knockout mice were subjected to an acute inflammatory stimulus via
      administration of LPS and the response of hepcidin and iron homeostasis was
      analysed. In the absence of IL-22, there was a response of hepcidin, resulting in
      a reduction in serum iron levels. However, the hypoferremic response to LPS was
      slightly blunted in mice lacking IL-22, suggesting that, during LPS-mediated
      inflammation, IL-22 may play a minor role in mediating the hypoferremic response.
      These results may have implications for the treatment and management of the ACD. 

PMID- 25568300
TI  - The phenotypic spectrum of SCN8A encephalopathy.
AB  - OBJECTIVE: SCN8A encodes the sodium channel voltage-gated alpha8-subunit
      (Nav1.6). SCN8A mutations have recently been associated with epilepsy and
      neurodevelopmental disorders. We aimed to delineate the phenotype associated with
      SCN8A mutations. METHODS: We used high-throughput sequence analysis of the SCN8A
      gene in 683 patients with a range of epileptic encephalopathies. In addition, we
      ascertained cases with SCN8A mutations from other centers. A detailed clinical
      history was obtained together with a review of EEG and imaging data. RESULTS:
      Seventeen patients with de novo heterozygous mutations of SCN8A were studied.
      Seizure onset occurred at a mean age of 5 months (range: 1 day to 18 months); in
      general, seizures were not triggered by fever. Fifteen of 17 patients had
      multiple seizure types including focal, tonic, clonic, myoclonic and absence
      seizures, and epileptic spasms; seizures were refractory to antiepileptic
      therapy. Development was normal in 12 patients and slowed after seizure onset,
      often with regression; 5 patients had delayed development from birth. All
      patients developed intellectual disability, ranging from mild to severe. Motor
      manifestations were prominent including hypotonia, dystonia, hyperreflexia, and
      ataxia. EEG findings comprised moderate to severe background slowing with focal
      or multifocal epileptiform discharges. CONCLUSION: SCN8A encephalopathy presents
      in infancy with multiple seizure types including focal seizures and spasms in
      some cases. Outcome is often poor and includes hypotonia and movement disorders.
      The majority of mutations arise de novo, although we observed a single case of
      somatic mosaicism in an unaffected parent.

PMID- 25568303
TI  - Drak2 is not required for tumor surveillance and suppression.
AB  - Drak2 is a promising therapeutic target to treat organ-specific autoimmune
      diseases such as type 1 diabetes and multiple sclerosis without causing
      generalized immune suppression. Inhibition of Drak2 may also prevent graft
      rejection following organ transplantation. However, Drak2 may function as a
      critical tumor suppressor, which would challenge the prospect of targeting Drak2
      for therapeutic treatment. Thus, we examined the susceptibility of Drak2 (-/-)
      mice in several tumor models. We show that Drak2 is not required to prevent tumor
      formation in a variety of settings. Therefore, Drak2 does not function as an
      essential tumor suppressor in in vivo tumor models. These data further validate
      Drak2 as a viable therapeutic target to treat autoimmune disease and graft
      rejection. Importantly, these data also indicate that while Drak2 may induce
      apoptosis when overexpressed in cell lines, it is not an essential tumor
      suppressor. 

PMID- 25568305
TI  - Telomerase activity and telomere length in male germ cells.
AB  - Telomeres are located at the outermost ends of all eukaryotic chromosomes and
      provide for the maintenance of genomic stability and integrity during the life
      span of organisms. The length of telomeres shortens due to each round of DNA
      replication, genotoxic insults, and/or reactive oxygen species. To counteract
      this shortening, certain types of cells, including stem cells, male/female
      germline cells, granulosa cells, early embryos, and most cancerous cells, express
      an enzyme known as telomerase, which has the potential of restoring the shortened
      telomeres. Presence of telomerase activity in the male germ cells ensures
      maintenance of telomere length at maximum levels during spermatogenesis despite
      telomere attrition due to DNA replication or other genotoxic factors. In this
      review, telomerase activity and telomere length in mammalian male germ cells
      during spermatogenesis are evaluated in detail based on the studies in this
      field. Also, the relationship between telomerase activity/telomere length and
      development of male infertility is comprehensively discussed. 

PMID- 25568304
TI  - Transcriptional and translational heterogeneity among neonatal mouse
      spermatogonia.
AB  - Spermatogonial stem cells (SSCs) are a subset of undifferentiated spermatogonia
      responsible for ongoing spermatogenesis in mammalian testes. Spermatogonial stem
      cells arise from morphologically homogeneous prospermatogonia, but growing
      evidence suggests that only a subset of prospermatogonia develops into the
      foundational SSC pool. This predicts that subtypes of undifferentiated
      spermatogonia with discrete mRNA and protein signatures should be distinguishable
      in neonatal testes. We used single-cell quantitative RT-PCR to examine mRNA
      levels of 172 genes in individual spermatogonia from 6-day postnatal (P6) mouse
      testes. Cells enriched from P6 testes using the StaPut or THY1(+) magnetic cell
      sorting methods exhibited considerable heterogeneity in the abundance of specific
      germ cell and stem cell mRNAs, segregating into one somatic and three distinct
      spermatogonial clusters. However, P6 Id4-eGFP(+) transgenic spermatogonia, which
      are known to be enriched for SSCs, were more homogeneous in their mRNA levels,
      exhibiting uniform levels for the majority of genes examined (122 of 172).
      Interestingly, these cells displayed nonuniform (50 of 172) expression of a
      smaller cohort of these genes, suggesting there is substantial heterogeneity even
      within the Id4-eGFP(+) population. Further, although immunofluorescence staining
      largely demonstrated conformity between mRNA and protein levels, some proteins
      were observed in patterns that were disparate from those detected for the
      corresponding mRNAs in Id4-eGFP(+) spermatogonia (e.g., Kit, Sohlh2, Stra8),
      suggesting additional heterogeneity is introduced at the posttranscriptional
      level. Taken together, these data demonstrate the existence of multiple
      spermatogonial subtypes in P6 mouse testes and raise the intriguing possibility
      that these subpopulations may correlate with the development of functionally
      distinct spermatogenic cell types. 

PMID- 25568308
TI  - Tricellulin and its role in the epididymal epithelium of the rat.
AB  - Tricellulin is a tight-junction protein present at tricellular tight junctions.
      It has been suggested that basal cells are implicated in the blood-epididymis
      barrier. Basal cells express claudins, a component of tight junctions; however,
      there is no information regarding the potential architecture or regulation of
      basal cell-principal cell interactions. The present objectives were to determine
      the expression and localization of tricellulin in rat epididymis in relation to
      occludin, basal cell-principal cell interactions, and other junctional proteins.
      Tricellulin levels were similar in all segments of the adult epididymis, and the
      protein was localized to the apical region of the epithelium. Postnatal
      development showed that tricellulin levels increased with age and localization
      changed from cytoplasmic to membrane-bound as a function of age. Colocalization
      with occludin indicated that both proteins are in the region of the tight
      junction. In the initial segment, the proteins did not colocalize compared to the
      epididymis where they were both colocalized. Tricellulin did not colocalize with
      cytokeratin 5, a marker of basal cells, in any region of the epididymis,
      including the corpus and cauda epididymidis, where apical projections of basal
      cells were apparent. Tricellulin knockdown studies using small interfering RNA in
      rat caput epididymal principal cells resulted in decreased transepithelial
      resistance and was correlated with decreased levels of Cldn3, Cldn1, and
      occludin. Tight-junction protein1, also known as ZO-1, and cadherin1 levels were
      unchanged. This is the first report of tricellulin in the epididymis and on the
      interaction between tricellulin and other tight-junction proteins. 

PMID- 25568306
TI  - Identifying a novel role for X-prolyl aminopeptidase (Xpnpep) 2 in CrVI-induced
      adverse effects on germ cell nest breakdown and follicle development in rats.
AB  - Environmental exposure to endocrine-disrupting chemicals (EDCs) is one cause of
      premature ovarian failure (POF). Hexavalent chromium (CrVI) is a heavy metal EDC
      widely used in more than 50 industries, including chrome plating, welding, wood
      processing, and tanneries. Recent data from U.S. Environmental Protection Agency
      indicate increased levels of Cr in drinking water from several American cities,
      which potentially predispose residents to various health problems. Recently, we
      demonstrated that gestational exposure to CrVI caused POF in F1 offspring. The
      current study was performed to identify the molecular mechanism behind CrVI
      induced POF. Pregnant rats were treated with 25 ppm of potassium dichromate from
      Gestational Day (GD) 9.5 to GD 14.5 through drinking water, and the fetuses were
      exposed to CrVI through transplacental transfer. Ovaries were removed from the
      fetuses or pups on Embryonic Day (ED) 15.5, ED 17.5, Postnatal Day (PND) 1, PND
      4, or PND 25, and various analyses were performed. Results showed that
      gestational exposure to CrVI: 1) increased germ cell/oocyte apoptosis and
      advanced germ cell nest (GCN) breakdown; 2) increased X-prolyl aminopeptidase
      (Xpnpep) 2, a POF marker in humans, during GCN breakdown; 3) decreased Xpnpep2
      during postnatal follicle development; and 4) increased colocalization of Xpnpep2
      with Col3 and Col4. We also found that Xpnpep2 inversely regulated the expression
      of Col1, Col3, and Col4 in all the developmental stages studied. Thus, CrVI
      advanced GCN breakdown and increased follicle atresia in F1 female progeny by
      targeting Xpnpep2. 

PMID- 25568307
TI  - Targeted disruption of glycogen synthase kinase 3A (GSK3A) in mice affects sperm
      motility resulting in male infertility.
AB  - The signaling enzyme glycogen synthase kinase 3 (GSK3) exists as two isoforms
      GSK3A and GSK3B. Protein phosphorylation by GSK3 has important signaling roles in
      several cells. In our past work, we found that both isoforms of GSK3 are present
      in mouse sperm and that catalytic GSK3 activity correlates with motility of sperm
      from several species. Here, we examined the role of Gsk3a in male fertility using
      a targeted gene knockout (KO) approach. The mutant mice are viable, but have a
      male infertility phenotype, while female fertility is unaffected. Testis weights
      of Gsk3a(-/-) mice are normal and sperm are produced in normal numbers. Although
      spermatogenesis is apparently unimpaired, sperm motility parameters in vitro are
      impaired. In addition, the flagellar waveform appears abnormal, characterized by
      low amplitude of flagellar beat. Sperm ATP levels were lower in Gsk3a(-/-) mice
      compared to wild-type animals. Protein phosphatase PP1 gamma2 protein levels were
      unaltered, but its catalytic activity was elevated in KO sperm. Remarkably,
      tyrosine phosphorylation of hexokinase and capacitation-associated changes in
      tyrosine phosphorylation of proteins are absent or significantly lower in Gsk3a(
      /-) sperm. The GSK3B isoform was present and unaltered in testis and sperm of
      Gsk3a(-/-) mice, showing the inability of GSK3B to substitute for GSK3A in this
      context. Our studies show that sperm GSK3A is essential for male fertility. In
      addition, the GSK3A isoform, with its highly conserved glycine-rich N terminus in
      mammals, may have an isoform-specific role in its requirement for normal sperm
      motility and fertility. 

PMID- 25568301
TI  - Mild cognitive impairment with suspected nonamyloid pathology (SNAP): Prediction
      of progression.
AB  - OBJECTIVES: The aim of this study was to investigate predictors of progressive
      cognitive deterioration in patients with suspected non-Alzheimer disease
      pathology (SNAP) and mild cognitive impairment (MCI). METHODS: We measured
      markers of amyloid pathology (CSF beta-amyloid 42) and neurodegeneration
      (hippocampal volume on MRI and cortical metabolism on [(18)F]-fluorodeoxyglucose
      PET) in 201 patients with MCI clinically followed for up to 6 years to detect
      progressive cognitive deterioration. We categorized patients with MCI as A+/A-
      and N+/N- based on presence/absence of amyloid pathology and neurodegeneration.
      SNAPs were A-N+ cases. RESULTS: The proportion of progressors was 11% (8/41), 34%
      (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+,
      respectively; the proportion of APOE epsilon4 carriers was 29%, 70%, 31%, and
      71%, respectively, with the SNAP group featuring a significantly different
      proportion than both A+N- and A+N+ groups (p <= 0.005). Hypometabolism in SNAP
      patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy
      was more severe in SNAP patients (p = 0.002). Compared with A-N-, SNAP and A+N+
      patients had significant risk of progressive cognitive deterioration (hazard
      ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N- patients did not
      (hazard ratio = 1.13, p = 0.771). In A+N- and A+N+ groups, none of the biomarkers
      predicted time to progression. In the SNAP group, lower time to progression was
      correlated with greater hypometabolism (r = 0.42, p = 0.073). CONCLUSIONS: Our
      findings support the notion that patients with SNAP MCI feature a specific risk
      progression profile.

PMID- 25568309
TI  - Nucleoid occlusion protein Noc recruits DNA to the bacterial cell membrane.
AB  - To proliferate efficiently, cells must co-ordinate division with chromosome
      segregation. In Bacillus subtilis, the nucleoid occlusion protein Noc binds to
      specific DNA sequences (NBSs) scattered around the chromosome and helps to
      protect genomic integrity by coupling the initiation of division to the
      progression of chromosome replication and segregation. However, how it inhibits
      division has remained unclear. Here, we demonstrate that Noc associates with the
      cell membrane via an N-terminal amphipathic helix, which is necessary for
      function. Importantly, the membrane-binding affinity of this helix is weak and
      requires the assembly of nucleoprotein complexes, thus establishing a mechanism
      for DNA-dependent activation of Noc. Furthermore, division inhibition by Noc
      requires recruitment of NBS DNA to the cell membrane and is dependent on its
      ability to bind DNA and membrane simultaneously. Indeed, Noc production in a
      heterologous system is sufficient for recruitment of chromosomal DNA to the
      membrane. Our results suggest a simple model in which the formation of large
      membrane-associated nucleoprotein complexes physically occludes assembly of the
      division machinery.

PMID- 25568310
TI  - NTR1 is required for transcription elongation checkpoints at alternative exons in
      Arabidopsis.
AB  - The interconnection between transcription and splicing is a subject of intense
      study. We report that Arabidopsis homologue of spliceosome disassembly factor
      NTR1 is required for correct expression and splicing of DOG1, a regulator of seed
      dormancy. Global splicing analysis in atntr1 mutants revealed a bias for
      downstream 5' and 3' splice site selection and an enhanced rate of exon skipping.
      A local reduction in PolII occupancy at misspliced exons and introns in atntr1
      mutants suggests that directionality in splice site selection is a manifestation
      of fast PolII elongation kinetics. In agreement with this model, we found AtNTR1
      to bind target genes and co-localise with PolII. A minigene analysis further
      confirmed that strong alternative splice sites constitute an AtNTR1-dependent
      transcriptional roadblock. Plants deficient in PolII endonucleolytic cleavage
      showed opposite effects for splice site choice and PolII occupancy compared to
      atntr1 mutants, and inhibition of PolII elongation or endonucleolytic cleavage in
      atntr1 mutant resulted in partial reversal of splicing defects. We propose that
      AtNTR1 is part of a transcription elongation checkpoint at alternative exons in
      Arabidopsis. 

PMID- 25568311
TI  - Phosphorylation of TET proteins is regulated via O-GlcNAcylation by the O-linked
      N-acetylglucosamine transferase (OGT).
AB  - TET proteins oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5
      formylcytosine, and 5-carboxylcytosine and thus provide a possible means for
      active DNA demethylation in mammals. Although their catalytic mechanism is well
      characterized and the catalytic dioxygenase domain is highly conserved, the
      function of the regulatory regions (the N terminus and the low-complexity insert
      between the two parts of the dioxygenase domains) is only poorly understood.
      Here, we demonstrate that TET proteins are subject to a variety of post
      translational modifications that mostly occur at these regulatory regions. We
      mapped TET modification sites at amino acid resolution and show for the first
      time that TET1, TET2, and TET3 are highly phosphorylated. The O-linked GlcNAc
      transferase, which we identified as a strong interactor with all three TET
      proteins, catalyzes the addition of a GlcNAc group to serine and threonine
      residues of TET proteins and thereby decreases both the number of phosphorylation
      sites and site occupancy. Interestingly, the different TET proteins display
      unique post-translational modification patterns, and some modifications occur in
      distinct combinations. In summary, our results provide a novel potential
      mechanism for TET protein regulation based on a dynamic interplay of
      phosphorylation and O-GlcNAcylation at the N terminus and the low-complexity
      insert region. Our data suggest strong cross-talk between the modification sites
      that could allow rapid adaption of TET protein localization, activity, or
      targeting due to changing environmental conditions as well as in response to
      external stimuli. 

PMID- 25568312
TI  - Functional role of RNA polymerase II and P70 S6 kinase in KCl withdrawal-induced
      cerebellar granule neuron apoptosis.
AB  - KCl withdrawal-induced apoptosis in cerebellar granule neurons is associated with
      aberrant cell cycle activation, and treatment with cyclin-dependent kinase (Cdk)
      inhibitors protects cells from undergoing apoptosis. Because the Cdk inhibitor
      flavopiridol is known to inhibit RNA polymerase II (Pol II)-dependent
      transcription elongation by inhibiting the positive transcription elongation
      factor b (P-TEFb, a complex of CDK9 and cyclin T), we examined whether inhibition
      of RNA Pol II protects neurons from apoptosis. Treatment of neurons with 5, 6
      dichloro-1-beta-D-ribobenzimidazole (DRB), an RNA Pol II-dependent transcription
      elongation inhibitor, and flavopiridol inhibited phosphorylation and activation
      of Pol II and protected neurons from undergoing apoptosis. In addition to Pol II,
      neurons subjected to KCl withdrawal showed increased phosphorylation and
      activation of p70 S6 kinase, which was inhibited by both DRB and flavopiridol.
      Immunostaining analysis of the neurons deprived of KCl showed increased nuclear
      levels of phospho-p70 S6 kinase, and neurons protected with DRB and flavopiridol
      showed accumulation of the kinase into large spliceosome assembly factor-positive
      speckle domains within the nuclei. The formation of these foci corresponded with
      cell survival, and removal of the inhibitors resulted in dispersal of the
      speckles into smaller foci with subsequent apoptosis induction. Because p70 S6
      kinase is known to induce translation of mRNAs containing a 5'-terminal
      oligopyrimidine tract, our data suggest that transcription and translation of
      this subset of mRNAs may contribute to KCl withdrawal-induced apoptosis in
      neurons.

PMID- 25568313
TI  - Deficiency of the chromatin regulator BRPF1 causes abnormal brain development.
AB  - Epigenetic mechanisms are important in different neurological disorders, and one
      such mechanism is histone acetylation. The multivalent chromatin regulator BRPF1
      (bromodomain- and plant homeodomain-linked (PHD) zinc finger-containing protein
      1) recognizes different epigenetic marks and activates three histone
      acetyltransferases, so it is both a reader and a co-writer of the epigenetic
      language. The three histone acetyltransferases are MOZ, MORF, and HBO1, which are
      also known as lysine acetyltransferase 6A (KAT6A), KAT6B, and KAT7, respectively.
      The MORF gene is mutated in four neurodevelopmental disorders sharing the
      characteristic of intellectual disability and frequently displaying callosal
      agenesis. Here, we report that forebrain-specific inactivation of the mouse Brpf1
      gene caused early postnatal lethality, neocortical abnormalities, and partial
      callosal agenesis. With respect to the control, the mutant forebrain contained
      fewer Tbr2-positive intermediate neuronal progenitors and displayed aberrant
      neurogenesis. Molecularly, Brpf1 loss led to decreased transcription of multiple
      genes, such as Robo3 and Otx1, important for neocortical development.
      Surprisingly, elevated expression of different Hox genes and various other
      transcription factors, such as Lhx4, Foxa1, Tbx5, and Twist1, was also observed.
      These results thus identify an important role of Brpf1 in regulating forebrain
      development and suggest that it acts as both an activator and a silencer of gene
      expression in vivo. 

PMID- 25568314
TI  - Structural and functional study of D-glucuronyl C5-epimerase.
AB  - Heparan sulfate (HS) is a glycosaminoglycan present on the cell surface and in
      the extracellular matrix, which interacts with diverse signal molecules and is
      essential for many physiological processes including embryonic development, cell
      growth, inflammation, and blood coagulation. D-glucuronyl C5-epimerase (Glce) is
      a crucial enzyme in HS synthesis, converting D-glucuronic acid to L-iduronic acid
      to increase HS flexibility. This modification of HS is important for protein
      ligand recognition. We have determined the crystal structures of Glce in apo-form
      (unliganded) and in complex with heparin hexasaccharide (product of Glce
      following O-sulfation), both in a stable dimer conformation. A Glce dimer
      contains two catalytic sites, each at a positively charged cleft in C-terminal
      alpha-helical domains binding one negatively charged hexasaccharide. Based on the
      structural and mutagenesis studies, three tyrosine residues, Tyr(468), Tyr(528),
      and Tyr(546), in the active site were found to be crucial for the enzymatic
      activity. The complex structure also reveals the mechanism of product inhibition
      (i.e. 2-O- and 6-O-sulfation of HS keeps the C5 carbon of L-iduronic acid away
      from the active-site tyrosine residues). Our structural and functional data
      advance understanding of the key modification in HS biosynthesis.

PMID- 25568315
TI  - Interplay between disulfide bonding and N-glycosylation defines SLC4 Na+-coupled
      transporter extracellular topography.
AB  - The extracellular loop 3 (EL-3) of SLC4 Na(+)-coupled transporters contains 4
      highly conserved cysteines and multiple N-glycosylation consensus sites. In the
      electrogenic Na(+)-HCO3(-) cotransporter NBCe1-A, EL-3 is the largest
      extracellular loop and is predicted to consist of 82 amino acids. To determine
      the structural-functional importance of the conserved cysteines and the N
      glycosylation sites in NBCe1-A EL-3, we analyzed the potential interplay between
      EL-3 disulfide bonding and N-glycosylation and their roles in EL-3 topological
      folding. Our results demonstrate that the 4 highly conserved cysteines form two
      intramolecular disulfide bonds, Cys(583)-Cys(585) and Cys(617)-Cys(642),
      respectively, that constrain EL-3 in a folded conformation. The formation of the
      second disulfide bond is spontaneous and unaffected by the N-glycosylation state
      of EL-3 or the first disulfide bond, whereas formation of the first disulfide
      bond relies on the presence of the second disulfide bond and is affected by N
      glycosylation. Importantly, EL-3 from each monomer is adjacently located at the
      NBCe1-A dimeric interface. When the two disulfide bonds are missing, EL-3 adopts
      an extended conformation highly accessible to protease digestion. This unique
      adjacent parallel location of two symmetrically folded EL-3 loops from each
      monomer resembles a domain-like structure that is potentially important for NBCe1
      A function in vivo. Moreover, the formation of this unique structure is
      critically dependent on the finely tuned interplay between disulfide bonding and
      N-glycosylation in the membrane processed NBCe1-A dimer.

PMID- 25568316
TI  - Activatory and inhibitory Fcgamma receptors augment rituximab-mediated
      internalization of CD20 independent of signaling via the cytoplasmic domain.
AB  - Type I anti-CD20 mAb such as rituximab and ofatumumab engage with the inhibitory
      FcgammaR, FcgammaRIIb on the surface of B cells, resulting in immunoreceptor
      tyrosine-based inhibitory motif (ITIM) phosphorylation. Internalization of the
      CD20.mAb.FcgammaRIIb complex follows, the rate of which correlates with
      FcgammaRIIb expression. In contrast, although type II anti-CD20 mAb such as
      tositumomab and obinutuzumab also interact with and activate FcgammaRIIb, this
      interaction fails to augment the rate of CD20.mAb internalization, raising the
      question of whether ITIM phosphorylation plays any role in this process. We have
      assessed the molecular requirements for the internalization process and
      demonstrate that in contrast to internalization of IgG immune complexes,
      FcgammaRIIb-augmented internalization of rituximab-ligated CD20 occurs
      independently of the FcgammaRIIb ITIM, indicating that signaling downstream of
      FcgammaRIIb is not required. In transfected cells, activatory FcgammaRI,
      FcgammaRIIa, and FcgammaRIIIa augmented internalization of rituximab-ligated CD20
      in a similar manner. However, FcgammaRIIa mediated a slower rate of
      internalization than cells expressing equivalent levels of the highly homologous
      FcgammaRIIb. The difference was maintained in cells expressing FcgammaRIIa and
      FcgammaRIIb lacking cytoplasmic domains and in which the transmembrane domains
      had been exchanged. This difference may be due to increased degradation of
      FcgammaRIIa, which traffics to lysosomes independently of rituximab. We conclude
      that the cytoplasmic domain of FcgammaR is not required for promoting
      internalization of rituximab-ligated CD20. Instead, we propose that FcgammaR
      provides a structural role in augmenting endocytosis that differs from that
      employed during the endocytosis of immune complexes. 

PMID- 25568317
TI  - The alphavbeta6 integrin is transferred intercellularly via exosomes.
AB  - Exosomes, cell-derived vesicles of endosomal origin, are continuously released in
      the extracellular environment and play a key role in intercellular crosstalk. In
      this study, we have investigated whether transfer of integrins through exosomes
      between prostate cancer (PrCa) cells occurs and whether transferred integrins
      promote cell adhesion and migration. Among others, we have focused on the
      alphavbeta6 integrin, which is not detectable in normal human prostate but is
      highly expressed in human primary PrCa as well as murine PrCa in Pten(pc-/-)
      mice. After confirming the fidelity of the exosome preparations by electron
      microscopy, density gradient, and immunoblotting, we determined that the
      alphavbeta6 integrin is actively packaged into exosomes isolated from PC3 and
      RWPE PrCa cell lines. We also demonstrate that alphavbeta6 is efficiently
      transferred via exosomes from a donor cell to an alphavbeta6-negative recipient
      cell and localizes to the cell surface. De novo alphavbeta6 expression in an
      alphavbeta6-negative recipient cell is not a result of a change in mRNA levels
      but is a consequence of exosome-mediated transfer of this integrin between
      different PrCa cells. Recipient cells incubated with exosomes containing
      alphavbeta6 migrate on an alphavbeta6 specific substrate, latency-associated
      peptide-TGFbeta, to a greater extent than cells treated with exosomes in which
      alphavbeta6 is stably or transiently down-regulated by shRNA or siRNA,
      respectively. Overall, this study shows that exosomes from PrCa cells may
      contribute to a horizontal propagation of integrin-associated phenotypes, which
      would promote cell migration, and consequently, metastasis in a paracrine
      fashion. 

PMID- 25568318
TI  - Dexamethasone promotes hypertension by allele-specific regulation of the human
      angiotensinogen gene.
AB  - The human angiotensinogen (hAGT) gene has polymorphisms in its 2.5-kb promoter
      that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, and -1561T/C)
      and -217A/G (-532T/C, -793A/G, -1074T/C, and -1178G/A). Hap -6A/-217A is
      associated with human hypertension, whereas Hap -6G/-217G reduces cardiovascular
      risk. Hap -6A/-217A has increased promoter activity with enhanced transcription
      factor binding, including to the glucocorticoid receptor (GR). Glucocorticoid
      therapy frequently causes hypertension, the mechanisms for which are incompletely
      understood. We have engineered double transgenic (TG) mice containing the human
      renin gene with either Hap of the hAGT gene and examined the physiological
      significance of glucocorticoid-mediated allele-specific regulation of the hAGT
      gene. We have also studied the consequential effects on the renin angiotensin
      system and blood pressure. TG mice with Hap -6A and -6G were treated with and
      without a low dose of a GR agonist, dexamethasone (2.5 MUg/ml), for 72 h. We
      found greater chromatin-GR binding with increased GR agonist-induced hAGT
      expression in liver and renal tissues of Hap -6A mice. Additionally,
      dexamethasone treatment increased circulating hAGT and angiotensin II levels in
      Hap -6A mice, as compared with -6G mice. Importantly, GR agonist significantly
      increased blood pressure and redox markers in TG mice with Hap-6A of the hAGT
      gene. Taken together, our results show, for the first time, that glucocorticoids
      affect hAGT expression in a haplotype-dependent fashion with SNPs in Hap -6A
      favoring agonist-induced GR binding. This leads to increased expression of the
      hAGT, up-regulation of the renin angiotensin system, and increased blood pressure
      and oxidative stress in Hap -6A mice. 

PMID- 25568319
TI  - Crystal structures capture three states in the catalytic cycle of a pyridoxal
      phosphate (PLP) synthase.
AB  - PLP synthase (PLPS) is a remarkable single-enzyme biosynthetic pathway that
      produces pyridoxal 5'-phosphate (PLP) from glutamine, ribose 5-phosphate, and
      glyceraldehyde 3-phosphate. The intact enzyme includes 12 synthase and 12
      glutaminase subunits. PLP synthesis occurs in the synthase active site by a
      complicated mechanism involving at least two covalent intermediates at a
      catalytic lysine. The first intermediate forms with ribose 5-phosphate. The
      glutaminase subunit is a glutamine amidotransferase that hydrolyzes glutamine and
      channels ammonia to the synthase active site. Ammonia attack on the first
      covalent intermediate forms the second intermediate. Glyceraldehyde 3-phosphate
      reacts with the second intermediate to form PLP. To investigate the mechanism of
      the synthase subunit, crystal structures were obtained for three intermediate
      states of the Geobacillus stearothermophilus intact PLPS or its synthase subunit.
      The structures capture the synthase active site at three distinct steps in its
      complicated catalytic cycle, provide insights into the elusive mechanism, and
      illustrate the coordinated motions within the synthase subunit that separate the
      catalytic states. In the intact PLPS with a Michaelis-like intermediate in the
      glutaminase active site, the first covalent intermediate of the synthase is fully
      sequestered within the enzyme by the ordering of a generally disordered 20
      residue C-terminal tail. Following addition of ammonia, the synthase active site
      opens and admits the Lys-149 side chain, which participates in formation of the
      second intermediate and PLP. Roles are identified for conserved Asp-24 in the
      formation of the first intermediate and for conserved Arg-147 in the conversion
      of the first to the second intermediate. 

PMID- 25568320
TI  - Activation of the UPR protects against cigarette smoke-induced RPE apoptosis
      through up-regulation of Nrf2.
AB  - Recent studies have revealed a role of endoplasmic reticulum (ER) stress-induced
      unfolded protein response (UPR) in the regulation of RPE cell activity and
      survival. Herein, we examined the mechanisms by which the UPR modulates apoptotic
      signaling in human RPE cells challenged with cigarette smoking extract (CSE). Our
      results show that CSE exposure induced a dose- and time-dependent increase in ER
      stress markers, enhanced reactive oxygen species (ROS), mitochondrial
      fragmentation, and apoptosis of RPE cells. These changes were prevented by the
      anti-oxidant NAC or chemical chaperone TMAO, suggesting a close interaction
      between oxidative and ER stress in CSE-induced apoptosis. To decipher the role of
      the UPR, overexpression or down-regulation of XBP1 and CHOP genes was manipulated
      by adenovirus or siRNA. Overexpressing XBP1 protected against CSE-induced
      apoptosis by reducing CHOP, p-p38, and caspase-3 activation. In contrast, XBP1
      knockdown sensitized the cells to CSE-induced apoptosis, which is likely through
      a CHOP-independent pathway. Surprisingly, knockdown of CHOP reduced p-eIF2alpha
      and Nrf2 resulting in a marked increase in caspase-3 activation and apoptosis.
      Furthermore, Nrf2 inhibition increased ER stress and exacerbated cell apoptosis,
      while Nrf2 overexpression reduced CHOP and protected RPE cells. Our data suggest
      that although CHOP may function as a pro-apoptotic gene during ER stress, it is
      also required for Nrf2 up-regulation and RPE cell survival. In addition,
      enhancing Nrf2 and XBP1 activity may help reduce oxidative and ER stress and
      protect RPE cells from cigarette smoke-induced damage. 

PMID- 25568321
TI  - GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate) is the preferred substrate for
      chondroitin N-acetylgalactosaminyltransferase-1.
AB  - A deficiency in chondroitin N-acetylgalactosaminyltransferase-1 (ChGn-1) was
      previously shown to reduce the number of chondroitin sulfate (CS) chains, leading
      to skeletal dysplasias in mice, suggesting that ChGn-1 regulates the number of CS
      chains for normal cartilage development. Recently, we demonstrated that 2
      phosphoxylose phosphatase (XYLP) regulates the number of CS chains by
      dephosphorylating the Xyl residue in the glycosaminoglycan-protein linkage region
      of proteoglycans. However, the relationship between ChGn-1 and XYLP in
      controlling the number of CS chains is not clear. In this study, we for the first
      time detected a phosphorylated tetrasaccharide linkage structure, GlcUAbeta1
      3Galbeta1-3Galbeta1-4Xyl(2-O-phosphate), in ChGn-1(-/-) growth plate cartilage
      but not in ChGn-2(-/-) or wild-type growth plate cartilage. In contrast, the
      truncated linkage tetrasaccharide GlcUAbeta1-3Galbeta1-3Galbeta1-4Xyl was
      detected in wild-type, ChGn-1(-/-), and ChGn-2(-/-) growth plate cartilage.
      Consistent with the findings, ChGn-1 preferentially transferred N
      acetylgalactosamine to the phosphorylated tetrasaccharide linkage in vitro.
      Moreover, ChGn-1 and XYLP interacted with each other, and ChGn-1-mediated
      addition of N-acetylgalactosamine was accompanied by rapid XYLP-dependent
      dephosphorylation during formation of the CS linkage region. Taken together, we
      conclude that the phosphorylated tetrasaccharide linkage is the preferred
      substrate for ChGn-1 and that ChGn-1 and XYLP cooperatively regulate the number
      of CS chains in growth plate cartilage. 

PMID- 25568323
TI  - The S228P mutation prevents in vivo and in vitro IgG4 Fab-arm exchange as
      demonstrated using a combination of novel quantitative immunoassays and
      physiological matrix preparation.
AB  - Human immunoglobulin G isotype 4 (IgG4) antibodies (Abs) are potential candidates
      for immunotherapy when reduced effector functions are desirable. IgG4 Abs are
      dynamic molecules able to undergo a process known as Fab arm exchange (FAE). This
      results in functionally monovalent, bispecific antibodies (bsAbs) with unknown
      specificity and hence, potentially, reduced therapeutic efficacy. IgG4 FAE is
      suggested to be an important biological mechanism that provides the basis for the
      anti-inflammatory activity attributed to IgG4 Abs. To date, the mechanism of FAE
      is not entirely understood and studies measuring FAE in ex vivo matrices have
      been hampered by the presence and abundance of endogenous IgG4 wild-type (WT)
      Abs. Using representative humanized WT IgG4 monoclonal Abs, namely, anti-IL-6 and
      anti-TNF, and a core-hinge stabilized serine 228 to proline (S228P) anti-IL-6
      IgG4 mutant, it is demonstrated for the first time how anti-IgG4 affinity
      chromatography can be used to prepare physiologically relevant matrices for
      assessing and quantifying FAE. A novel method for quantifying FAE using a single
      MSD immunoassay is also reported and confirms previous findings that, dependent
      on the redox conditions, the S228P mutation can prevent IgG4 FAE to undetectable
      levels both in vitro and in vivo. Together, the findings and novel methodologies
      will allow researchers to monitor and quantify FAE of their own IgG4 molecules in
      physiologically relevant matrices. 

PMID- 25568322
TI  - Discovery, primary, and crystal structures and capacitation-related properties of
      a prostate-derived heparin-binding protein WGA16 from boar sperm.
AB  - Mammalian sperm acquire fertility through a functional maturation process called
      capacitation, where sperm membrane molecules are drastically remodeled. In this
      study, we found that a wheat germ agglutinin (WGA)-reactive protein on lipid
      rafts, named WGA16, is removed from the sperm surface on capacitation. WGA16 is a
      prostate-derived seminal plasma protein that has never been reported and is
      deposited on the sperm surface in the male reproductive tract. Based on protein
      and cDNA sequences for purified WGA16, it is a homologue of human zymogen granule
      protein 16 (ZG16) belonging to the Jacalin-related lectin (JRL) family in crystal
      and primary structures. A glycan array shows that WGA16 binds heparin through a
      basic patch containing Lys-53/Lys-73 residues but not the conventional lectin
      domain of the JRL family. WGA16 is glycosylated, contrary to other ZG16 members,
      and comparative mass spectrometry clearly shows its unique N-glycosylation
      profile among seminal plasma proteins. It has exposed GlcNAc and GalNAc residues
      without additional Gal residues. The GlcNAc/GalNAc residues can work as binding
      ligands for a sperm surface galactosyltransferase, which actually galactosylates
      WGA16 in situ in the presence of UDP-Gal. Interestingly, surface removal of WGA16
      is experimentally induced by either UDP-Gal or heparin. In the crystal structure,
      N-glycosylated sites and a potential heparin-binding site face opposite sides.
      This geography of two functional sites suggest that WGA16 is deposited on the
      sperm surface through interaction between its N-glycans and the surface
      galactosyltransferase, whereas its heparin-binding domain may be involved in
      binding to sulfated glycosaminoglycans in the female tract, enabling removal of
      WGA16 from the sperm surface. 

PMID- 25568324
TI  - Lipopolysaccharide (LPS)-mediated angiopoietin-2-dependent autocrine angiogenesis
      is regulated by NADPH oxidase 2 (Nox2) in human pulmonary microvascular
      endothelial cells.
AB  - Sepsis-mediated endothelial Angiopoeitin-2 (Ang2) signaling may contribute to
      microvascular remodeling in the developing lung. The mechanisms by which
      bacterial cell wall components such as LPS mediate Ang2 signaling in human
      pulmonary microvascular endothelial cells (HPMECs) remain understudied. In HPMEC,
      LPS-induced Ang2, Tie2, and VEGF-A protein expression was preceded by increased
      superoxide formation. NADPH oxidase 2 (Nox2) inhibition, but not Nox4 or Nox1
      inhibition, attenuated LPS-induced superoxide formation and Ang2, Tie2, and VEGF
      A expression. Nox2 silencing, but not Nox4 or Nox1 silencing, inhibited LPS
      mediated inhibitor of kappa-B kinase beta (IKKbeta) and p38 phosphorylation and
      nuclear translocation of NF-kappaB and AP-1. In HPMECs, LPS increased the number
      of angiogenic tube and network formations in Matrigel by >3-fold. Conditioned
      media from LPS-treated cells also induced angiogenic tube and network formation
      in the presence of Toll-like receptor 4 blockade but not in the presence of Ang2
      and VEGF blockade. Nox2 inhibition or conditioned media from Nox2-silenced cells
      attenuated LPS-induced tube and network formation. Ang2 and VEGF-A treatment
      rescued angiogenesis in Nox2-silenced cells. We propose that Nox2 regulates LPS
      mediated Ang2-dependent autocrine angiogenesis in HPMECs through the IKKbeta/NF
      kappaB and MAPK/AP-1 pathways. 

PMID- 25568325
TI  - Probing the acceptor active site organization of the human recombinant beta1,4
      galactosyltransferase 7 and design of xyloside-based inhibitors.
AB  - Among glycosaminoglycan (GAG) biosynthetic enzymes, the human beta1,4
      galactosyltransferase 7 (hbeta4GalT7) is characterized by its unique capacity to
      take over xyloside derivatives linked to a hydrophobic aglycone as substrates
      and/or inhibitors. This glycosyltransferase is thus a prime target for the
      development of regulators of GAG synthesis in therapeutics. Here, we report the
      structure-guided design of hbeta4GalT7 inhibitors. By combining molecular
      modeling, in vitro mutagenesis, and kinetic measurements, and in cellulo analysis
      of GAG anabolism and decorin glycosylation, we mapped the organization of the
      acceptor binding pocket, in complex with 4-methylumbelliferone-xylopyranoside as
      prototype substrate. We show that its organization is governed, on one side, by
      three tyrosine residues, Tyr(194), Tyr(196), and Tyr(199), which create a
      hydrophobic environment and provide stacking interactions with both
      xylopyranoside and aglycone rings. On the opposite side, a hydrogen-bond network
      is established between the charged amino acids Asp(228), Asp(229), and Arg(226),
      and the hydroxyl groups of xylose. We identified two key structural features,
      i.e. the strategic position of Tyr(194) forming stacking interactions with the
      aglycone, and the hydrogen bond between the His(195) nitrogen backbone and the
      carbonyl group of the coumarinyl molecule to develop a tight binder of
      hbeta4GalT7. This led to the synthesis of 4-deoxy-4-fluoroxylose linked to 4
      methylumbelliferone that inhibited hbeta4GalT7 activity in vitro with a Ki 10
      times lower than the Km value and efficiently impaired GAG synthesis in a cell
      assay. This study provides a valuable probe for the investigation of GAG biology
      and opens avenues toward the development of bioactive compounds to correct GAG
      synthesis disorders implicated in different types of malignancies. 

PMID- 25568326
TI  - Transfected poly(I:C) activates different dsRNA receptors, leading to apoptosis
      or immunoadjuvant response in androgen-independent prostate cancer cells.
AB  - Despite the effectiveness of surgery or radiation therapy for the treatment of
      early-stage prostate cancer (PCa), there is currently no effective strategy for
      late-stage disease. New therapeutic targets are emerging; in particular, dsRNA
      receptors Toll-like receptor 3 (TLR3) and cytosolic helicases expressed by cancer
      cells, once activated, exert a pro-apoptotic effect in different tumors. We
      previously demonstrated that the synthetic analog of dsRNA poly(I:C) induces
      apoptosis in the androgen-dependent PCa cell line LNCaP in a TLR3-dependent
      fashion, whereas only a weak apoptotic effect is observed in the more aggressive
      and androgen-independent PCa cells PC3 and DU145. In this paper, we characterize
      the receptors and the signaling pathways involved in the remarkable apoptosis
      induced by poly(I:C) transfected by Lipofectamine (in-poly(I:C)) compared with
      the 12-fold higher free poly(I:C) concentration in PC3 and DU145 cells. By using
      genetic inhibition of different poly(I:C) receptors, we demonstrate the crucial
      role of TLR3 and Src in in-poly(I:C)-induced apoptosis. Therefore, we show that
      the increased in-poly(I:C) apoptotic efficacy is due to a higher binding of
      endosomal TLR3. On the other hand, we show that in-poly(I:C) binding to cytosolic
      receptors MDA5 and RIG-I triggers IRF3-mediated signaling, leading uniquely to
      the up-regulation of IFN-beta, which likely in turn induces increased TLR3, MDA5,
      and RIG-I proteins. In summary, in-poly(I:C) activates two distinct antitumor
      pathways in PC3 and DU145 cells: one mediated by the TLR3/Src/STAT1 axis, leading
      to apoptosis, and the other one mediated by MDA5/RIG-I/IRF3, leading to
      immunoadjuvant IFN-beta expression. 

PMID- 25568327
TI  - miR-28-3p is a cellular restriction factor that inhibits human T cell leukemia
      virus, type 1 (HTLV-1) replication and virus infection.
AB  - Human T cell leukemia virus, type 1 (HTLV-1) replication and spread are
      controlled by different viral and cellular factors. Although several anti-HIV
      cellular microRNAs have been described, such a regulation for HTLV-1 has not been
      reported. In this study, we found that miR-28-3p inhibits HTLV-1 virus expression
      and its replication by targeting a specific site within the genomic gag/pol viral
      mRNA. Because miR-28-3p is highly expressed in resting T cells, which are
      resistant to HTLV-1 infection, we investigated a potential protective role of miR
      28-3p against de novo HTLV-1 infection. To this end, we developed a new sensitive
      and quantitative assay on the basis of the detection of products of reverse
      transcription. We demonstrate that miR-28-3p does not prevent virus receptor
      interaction or virus entry but, instead, induces a post-entry block at the
      reverse transcription level. In addition, we found that HTLV-1, subtype 1A
      isolates corresponding to the Japanese strain ATK-1 present a natural, single
      nucleotide polymorphism within the miR-28-3p target site. As a result of this
      polymorphism, the ATK-1 virus sequence was not inhibited by miR-28.
      Interestingly, genetic studies on the transmission of the virus has shown that
      the ATK-1 strain, which carries a Thr-to-Cys transition mutation, is transmitted
      efficiently between spouses, suggesting that miR-28 may play an important role in
      HTLV-1 transmission. 

PMID- 25568329
TI  - Active endocannabinoids are secreted on extracellular membrane vesicles.
AB  - Endocannabinoids primarily influence neuronal synaptic communication within the
      nervous system. To exert their function, endocannabinoids need to travel across
      the intercellular space. However, how hydrophobic endocannabinoids cross cell
      membranes and move extracellularly remains an unresolved problem. Here, we show
      that endocannabinoids are secreted through extracellular membrane vesicles
      produced by microglial cells. We demonstrate that microglial extracellular
      vesicles carry on their surface N-arachidonoylethanolamine (AEA), which is able
      to stimulate type-1 cannabinoid receptors (CB1), and inhibit presynaptic
      transmission, in target GABAergic neurons. This is the first demonstration of a
      functional role of extracellular vesicular transport of endocannabinoids. 

PMID- 25568328
TI  - Role of the outer pore domain in transient receptor potential vanilloid 1 dynamic
      permeability to large cations.
AB  - Transient receptor potential vanilloid 1 (TRPV1) has been shown to alter its
      ionic selectivity profile in a time- and agonist-dependent manner. One hallmark
      of this dynamic process is an increased permeability to large cations such as N
      methyl-D-glucamine (NMDG). In this study, we mutated residues throughout the
      TRPV1 pore domain to identify loci that contribute to dynamic large cation
      permeability. Using resiniferatoxin (RTX) as the agonist, we identified multiple
      gain-of-function substitutions within the TRPV1 pore turret (N628P and S629A),
      pore helix (F638A), and selectivity filter (M644A) domains. In all of these
      mutants, maximum NMDG permeability was substantially greater than that recorded
      in wild type TRPV1, despite similar or even reduced sodium current density. Two
      additional mutants, located in the pore turret (G618W) and selectivity filter
      (M644I), resulted in significantly reduced maximum NMDG permeability. M644A and
      M644I also showed increased and decreased minimum NMDG permeability,
      respectively. The phenotypes of this panel of mutants were confirmed by imaging
      the RTX-evoked uptake of the large cationic fluorescent dye YO-PRO1. Whereas none
      of the mutations selectively altered capsaicin-induced changes in NMDG
      permeability, the loss-of-function phenotypes seen with RTX stimulation of G618W
      and M644I were recapitulated in the capsaicin-evoked YO-PRO1 uptake assay.
      Curiously, the M644A substitution resulted in a loss, rather than a gain, in
      capsaicin-evoked YO-PRO1 uptake. Modeling of our mutations onto the recently
      determined TRPV1 structure revealed several plausible mechanisms for the
      phenotypes observed. We conclude that side chain interactions at a few specific
      loci within the TRPV1 pore contribute to the dynamic process of ionic
      selectivity.

PMID- 25568331
TI  - The relationship between the frequency of football practice during skeletal
      growth and the presence of a cam deformity in adult elite football players.
AB  - BACKGROUND/AIM: Cam deformity (CD) is likely a bony adaptation in response to
      high-impact sports practice during skeletal growth. We ascertained whether a dose
      response relationship exists between the frequency of football practice during
      skeletal growth and the presence of a CD in adulthood, and if the age at which a
      football player starts playing football is associated with the presence of a CD
      in adulthood. METHODS: Prevalence of a CD (alpha angle>60 degrees ) and a
      pathological CD (alpha angle>78 degrees ) was studied using standardised
      anteroposterior (AP) and frog-leg lateral (FLL) radiographs that were obtained
      during seasonal screening. The age of starting to play football with a low
      frequency (LF; <=3 times/week) and high frequency (HF; >=4 times/week) was
      retrospectively assessed. The differences in prevalence of a CD per hip, in
      either view, between groups were calculated by logistic regression with
      generalised estimating equations. RESULTS: 63 players (mean(+/-SD) age 23.1(+/
      4.2) years) participated, yielding 126 hips for analysis. The prevalence of a CD
      in the FLL was 40% (n=82) in players who started playing HF football from the age
      of 12 years or above, and 64% (n=44) in those playing HF football before the age
      of 12 years (p=0.042). This was also true for a pathological CD (12% vs 30%,
      p=0.038). The AP views revealed no difference. CONCLUSIONS: Our results indicate
      a probable dose-response relationship between the frequency of football practice
      during skeletal growth and the development of a CD, which should be confirmed in
      future prospective studies.

PMID- 25568330
TI  - Health benefits of different sport disciplines for adults: systematic review of
      observational and intervention studies with meta-analysis.
AB  - The aim was to assess the quality and strength of evidence for the health
      benefits of specific sport disciplines. Electronic search yielded 2194 records
      and the selection resulted in 69 eligible studies (47 cross-sectional, 9 cohort,
      13 intervention studies). 105 comparisons between participation and non
      participation groups in 26 different sport disciplines were reported. Moderately
      strong evidence showed that both running and football improve aerobic fitness and
      cardiovascular function at rest, and football reduces adiposity. Conditional
      evidence showed that running benefits metabolic fitness, adiposity and postural
      balance, and football improves metabolic fitness, muscular performance, postural
      balance, and cardiac function. Evidence for health benefits of other sport
      disciplines was either inconclusive or tenuous. The evidence base for the health
      benefits of specific sports disciplines is generally compromised by weak study
      design and quality. Future research should address the health effects of
      different sport disciplines using rigorous research designs. 

PMID- 25568332
TI  - Treatment of subclinical hyperthyroidism: effect on left ventricular mass and
      function of the heart using magnetic resonance imaging technique.
AB  - PURPOSE: The aim of this study was to investigate structure and function of the
      heart in subclinical hyperthyroidism (SH) before and after obtaining euthyroidism
      by radioactive iodine treatment, using high precision and observer-independent
      magnetic resonance imaging (MRI) technology. METHODS: Cardiac MRI was performed
      before and after euthyroidism was obtained by radioactive iodine treatment in 12
      otherwise healthy patients (11 women and one man, mean age 59 years, range 44-71
      years) with a nodular goiter and SH, and compared with eight healthy controls
      investigated at baseline. Cardiac data were expressed as an index, as per body
      surface area, except for heart rate (HR) and ejection fraction. RESULTS: Post
      treatment cardiac MRI was performed in median 139 days after a normalized serum
      TSH value had been recorded. During treatment, serum TSH increased from (median
      (range)) 0.01 (0.01-0.09) to 0.88 (0.27-3.99) mU/l. Patients with untreated SH
      had increased resting HR (P<0.01) as well as cardiac index (cardiac output as per
      body surface area) (P<0.01) compared with controls. Obtaining euthyroidism
      resulted in a significant decrease in left ventricular mass index (LVMI) of 2.7
      g/m(2) (P=0.034), in HR of 8 bpm (P=0.001), and in cardiac index of 0.24 l/min
      per m(2) (P=0.017). CONCLUSIONS: Normalization of thyroid function by radioactive
      iodine treatment of SH resulted in significant reductions in clinically important
      heart parameters such as LVMI, HR, and cardiac index. SH should be regarded as a
      condition in which aggressive treatment should be considered to protect cardiac
      function.

PMID- 25568333
TI  - A mechanism of leading-edge protrusion in the absence of Arp2/3 complex.
AB  - Cells employ protrusive leading edges to navigate and promote their migration in
      diverse physiological environments. Classical models of leading-edge protrusion
      rely on a treadmilling dendritic actin network that undergoes continuous assembly
      nucleated by the Arp2/3 complex, forming ruffling lamellipodia. Recent work
      demonstrated, however, that, in the absence of the Arp2/3 complex, fibroblast
      cells adopt a leading edge with filopodia-like protrusions (FLPs) and maintain an
      ability to move, albeit with altered responses to different environmental
      signals. We show that formin-family actin nucleators are required for the
      extension of FLPs but are insufficient to produce a continuous leading edge in
      fibroblasts lacking Arp2/3 complex. Myosin II is concentrated in arc-like regions
      of the leading edge in between FLPs, and its activity is required for coordinated
      advancement of these regions with formin-generated FLPs. We propose that
      actomyosin contraction acting against membrane tension advances the web of arcs
      between FLPs. Predictions of this model are verified experimentally. The
      dependence of myosin II in leading-edge advancement helps explain the previously
      reported defect in directional movement in the Arpc3-null fibroblasts. We provide
      further evidence that this defect is cell autonomous during chemotaxis. 

PMID- 25568334
TI  - Inactivation of GSK3beta and activation of NF-kappaB pathway via Axl represents
      an important mediator of tumorigenesis in esophageal squamous cell carcinoma.
AB  - The receptor tyrosine kinase Axl has been described as an oncogene, and its
      deregulation has been implicated in the progression of several human cancers.
      While the role of Axl in esophageal adenocarcinoma has been addressed, there is
      no information about its role in esophageal squamous cell carcinoma (OSCC). In
      the current report, we identified, for the first time, deregulation of Axl
      expression in OSCC. Axl is consistently overexpressed in OSCC cell lines and
      human tumor samples, mainly in advanced stages of the disease. Blockage of Axl
      gene expression by small interfering RNA inhibits cell survival, proliferation,
      migration, and invasion in vitro and esophageal tumor growth in vivo.
      Additionally, repression of Axl expression results in Akt-dependent inhibition of
      pivotal genes involved in the nuclear factor-kappaB (NF-kappaB) pathway and in
      the induction of glycogen synthase kinase 3beta (GSK3beta) activity, resulting in
      loss of mesenchymal markers and induction of epithelial markers. Furthermore,
      treatment of esophageal cancer cells with the Akt inhibitor wortmannin inhibits
      NF-kappaB signaling, induces GSK3beta activity, and blocks OSCC cell
      proliferation in an Axl-dependent manner. Taken together, our results establish a
      clear role for Axl in OSCC tumorigenesis with potential therapeutic implications.

PMID- 25568336
TI  - USP19 deubiquitinating enzyme inhibits muscle cell differentiation by suppressing
      unfolded-protein response signaling.
AB  - The USP19 deubiquitinating enzyme modulates the expression of myogenin and
      myofibrillar proteins in L6 muscle cells. This raised the possibility that USP19
      might regulate muscle cell differentiation. We therefore tested the effects of
      adenoviral-mediated overexpression or small interfering RNA (siRNA)-mediated
      silencing of either the cytoplasmic or endoplasmic reticulum (ER)-localized
      isoforms of USP19. Only the ER-localized isoform of USP19 (USP19-ER) modulated
      myoblast fusion as well as the expression of myogenin and myofibrillar proteins,
      and these effects were also dependent on USP19 catalytic activity. USP19-ER
      inhibited muscle cell differentiation and the induction of CHOP, a transcription
      factor in the unfolded-protein response (UPR) that is activated during
      differentiation. Inducing the UPR by creating mild ER stress with thapsigargin
      was able to reverse the defect in myoblast fusion caused by the overexpression of
      USP19-ER, suggesting strongly that USP19 exerts its effects on fusion through its
      effects on UPR signaling. USP19 also functions similarly in vivo, as USP19(-/-)
      mice display improved muscle regeneration concomitant with enhanced expression of
      CHOP. Collectively these results implicate a deubiquitinating enzyme as a
      regulator of the UPR. They also suggest that inhibition of USP19 may be a
      therapeutic approach for the enhancement of muscle growth following injury.

PMID- 25568335
TI  - Rab31 and APPL2 enhance FcgammaR-mediated phagocytosis through PI3K/Akt signaling
      in macrophages.
AB  - Membrane remodeling in the early stages of phagocytosis enables the engulfment of
      particles or pathogens and receptor signaling to activate innate immune
      responses. Members of the Rab GTPase family and their disparate effectors are
      recruited sequentially to regulate steps throughout phagocytosis. Rab31 (Rab22b)
      is known for regulating post-Golgi trafficking, and here we show in macrophages
      that Rab31-GTP is additionally and specifically recruited to early-stage
      phagosomes. At phagocytic cups, Rab31 is first recruited during the
      phosphoinositide transition from PI(4,5)P2 to PI(3,4,5)P3, and it persists on
      PI(3)P-enriched phagosomes. During early phagocytosis, we find that Rab31
      recruits the signaling adaptor APPL2. siRNA depletion of either Rab31 or APPL2
      reduces FcgammaR-mediated phagocytosis. Mechanistically, this corresponds with a
      delay in the transition to PI(3,4,5)P3 and phagocytic cup closure. APPL2
      depletion also reduced PI3K/Akt signaling and enhanced p38 signaling from
      FcgammaR. We thus conclude that Rab31/APPL2 is required for key roles in
      phagocytosis and prosurvival responses of macrophages. Of interest, in terms of
      localization and function, this Rab31/APPL2 complex is distinct from the
      Rab5/APPL1 complex, which is also involved in phagocytosis and signaling. 

PMID- 25568337
TI  - Mechanical coupling between transsynaptic N-cadherin adhesions and actin flow
      stabilizes dendritic spines.
AB  - The morphology of neuronal dendritic spines is a critical indicator of synaptic
      function. It is regulated by several factors, including the intracellular
      actin/myosin cytoskeleton and transcellular N-cadherin adhesions. To examine the
      mechanical relationship between these molecular components, we performed
      quantitative live-imaging experiments in primary hippocampal neurons. We found
      that actin turnover and structural motility were lower in dendritic spines than
      in immature filopodia and increased upon expression of a nonadhesive N-cadherin
      mutant, resulting in an inverse relationship between spine motility and actin
      enrichment. Furthermore, the pharmacological stimulation of myosin II induced the
      rearward motion of actin structures in spines, showing that myosin II exerts
      tension on the actin network. Strikingly, the formation of stable, spine-like
      structures enriched in actin was induced at contacts between dendritic filopodia
      and N-cadherin-coated beads or micropatterns. Finally, computer simulations of
      actin dynamics mimicked various experimental conditions, pointing to the actin
      flow rate as an important parameter controlling actin enrichment in dendritic
      spines. Together these data demonstrate that a clutch-like mechanism between N
      cadherin adhesions and the actin flow underlies the stabilization of dendritic
      filopodia into mature spines, a mechanism that may have important implications in
      synapse initiation, maturation, and plasticity in the developing brain. 

PMID- 25568338
TI  - Distinct functionality of dishevelled isoforms on Ca2+/calmodulin-dependent
      protein kinase 2 (CamKII) in Xenopus gastrulation.
AB  - Wnt ligands trigger the activation of a variety of beta-catenin-dependent and
      beta-catenin-independent intracellular signaling cascades. Despite the variations
      in intracellular signaling, Wnt pathways share the effector proteins frizzled,
      dishevelled, and beta-arrestin. It is unclear how the specific activation of
      individual branches and the integration of multiple signals are achieved. We
      hypothesized that the composition of dishevelled-beta-arrestin protein complexes
      contributes to signal specificity and identified CamKII as an interaction partner
      of the dishevelled-beta-arrestin protein complex by quantitative functional
      proteomics. Specifically, we found that CamKII isoforms interact differentially
      with the three vertebrate dishevelled proteins. Dvl1 is required for the
      activation of CamKII and PKC in the Wnt/Ca(2+) pathway. However, CamKII interacts
      with Dvl2 but not with Dvl1, and Dvl2 is necessary to mediate CamKII function
      downstream of Dvl1 in convergent extension movements in Xenopus gastrulation. Our
      findings indicate that the different Dvl proteins and the composition of
      dishevelled-beta-arrestin protein complexes contribute to the specific activation
      of individual branches of Wnt signaling. 

PMID- 25568339
TI  - Misexpression of BRE gene in the developing chick neural tube affects neurulation
      and somitogenesis.
AB  - The brain and reproductive expression (BRE) gene is expressed in numerous adult
      tissues and especially in the nervous and reproductive systems. However, little
      is known about BRE expression in the developing embryo or about its role in
      embryonic development. In this study, we used in situ hybridization to reveal the
      spatiotemporal expression pattern for BRE in chick embryo during development. To
      determine the importance of BRE in neurogenesis, we overexpressed BRE and also
      silenced BRE expression specifically in the neural tube. We established that
      overexpressing BRE in the neural tube indirectly accelerated Pax7(+) somite
      development and directly increased HNK-1(+) neural crest cell (NCC) migration and
      TuJ-1(+) neurite outgrowth. These altered morphogenetic processes were associated
      with changes in the cell cycle of NCCs and neural tube cells. The inverse effect
      was obtained when BRE expression was silenced in the neural tube. We also
      determined that BMP4 and Shh expression in the neural tube was affected by
      misexpression of BRE. This provides a possible mechanism for how altering BRE
      expression was able to affect somitogenesis, neurogenesis, and NCC migration. In
      summary, our results demonstrate that BRE plays an important role in regulating
      neurogenesis and indirectly somite differentiation during early chick embryo
      development. 

PMID- 25568340
TI  - Up-regulation of BMP2/4 signaling increases both osteoblast-specific marker
      expression and bone marrow adipogenesis in Gja1Jrt/+ stromal cell cultures.
AB  - Gja1(Jrt)/+ mice carry a mutation in one allele of the gap junction protein
      alpha1 gene (Gja1), resulting in a G60S connexin 43 (Cx43) mutant protein that is
      dominant negative for Cx43 protein production of <50% of wild-type (WT) levels
      and significantly reduced gap junction formation and function in osteoblasts and
      other Cx43-expressing cells. Previously we reported that Gja1(Jrt)/+ mice
      exhibited early-onset osteopenia caused by activation of osteoclasts secondary to
      activation of osteoblast lineage cells, which expressed increased RANKL and
      produced an abnormal resorption-stimulating bone matrix high in BSP content.
      Gja1(Jrt)/+ mice also displayed early and progressive bone marrow atrophy, with a
      significant increase in bone marrow adiposity versus WT littermates but no
      increase in adipose tissues elsewhere in the body. BMP2/4 production and
      signaling were increased in Gja1(Jrt)/+ trabecular bone and osteogenic stromal
      cell cultures, which contributed to the up-regulated expression of osteoblast
      specific markers (e.g., Bsp and Ocn) in Gja1(Jrt)/+ osteoblasts and increased
      Pparg2 expression in bone marrow-derived adipoprogenitors in vitro. The elevated
      levels of BMP2/4 signaling in G60S Cx43-containing cells resulted at least in
      part from elevated levels of cAMP. We conclude that up-regulation of BMP2/4
      signaling in trabecular bone and/or stromal cells increases osteoblast-specific
      marker expression in hyperactive Gja1(Jrt)/+ osteoblasts and may also increase
      bone marrow adipogenesis by up-regulation of Pparg2 in the Cx43-deficient
      Gja1(Jrt)/+ mouse model. 

PMID- 25568341
TI  - Kif2a depletion generates chromosome segregation and pole coalescence defects in
      animal caps and inhibits gastrulation of the Xenopus embryo.
AB  - Kif2a is a member of the kinesin-13 microtubule depolymerases, which tightly
      regulate microtubule dynamics for many cellular processes. We characterized Kif2a
      depletion in Xenopus animal caps and embryos. Kif2a depletion generates defects
      in blastopore closure. These defects are rescued by removing the animal cap,
      suggesting that Kif2a-depleted animal caps are not compliant enough to allow
      gastrulation movements. Gastrulation defects are not rescued by a Kif2a mutated
      in an Aurora kinase phosphorylation site, suggesting that the phenotypes are
      caused by problems in mitosis. During animal cap mitoses, Kif2a localizes to the
      spindle poles and centromeres. Depletion of Kif2a generated multipolar spindles
      in stage 12 embryos. Kif2a-depleted animal caps have anaphase lagging chromosomes
      in stage 9 and 10 embryos and subsequent cytokinesis failure. Later divisions
      have greater than two centrosomes, generating extra spindle poles. Kif2a-depleted
      embryos are also defective at coalescing extra spindle poles into a bipolar
      spindle. The gastrulation and mitotic phenotypes can be rescued by either human
      Kif2a or Kif2b, which suggests that the two homologues redundantly regulate
      mitosis in mammals. These studies demonstrate that defects in mitosis can inhibit
      large-scale developmental movements in vertebrate tissues. 

PMID- 25568342
TI  - TRAF2 recruitment via T61 in CD30 drives NFkappaB activation and enhances hESC
      survival and proliferation.
AB  - CD30 (TNFRSF8), a tumor necrosis factor receptor family protein, and CD30 variant
      (CD30v), a ligand-independent form encoding only the cytoplasmic signaling
      domain, are concurrently overexpressed in transformed human embryonic stem cells
      (hESCs) or hESCs cultured in the presence of ascorbate. CD30 and CD30v are
      believed to increase hESC survival and proliferation through NFkappaB activation,
      but how this occurs is largely unknown. Here we demonstrate that hESCs that
      endogenously express CD30v and hESCs that artificially overexpress CD30v exhibit
      increased ERK phosphorylation levels, activation of the canonical NFkappaB
      pathway, down-regulation of the noncanonical NFkappaB pathway, and reduced
      expression of the full-length CD30 protein. We further find that CD30v,
      surprisingly, resides predominantly in the nucleus of hESC. We demonstrate that
      alanine substitution of a single threonine residue at position 61 (T61) in CD30v
      abrogates CD30v-mediated NFkappaB activation, CD30v-mediated resistance to
      apoptosis, and CD30v-enhanced proliferation, as well as restores normal G2/M
      checkpoint arrest upon H2O2 treatment while maintaining its unexpected
      subcellular distribution. Using an affinity purification strategy and LC-MS, we
      identified TRAF2 as the predominant protein that interacts with WT CD30v but not
      the T61A-mutant form in hESCs. The identification of Thr-61 as a critical residue
      for TRAF2 recruitment and canonical NFkappaB signaling by CD30v reveals the
      substantial contribution that this molecule makes to overall NFkappaB activity,
      cell cycle changes, and survival in hESCs. 

PMID- 25568343
TI  - Arp2/3 complex inhibition radically alters lamellipodial actin architecture,
      suspended cell shape, and the cell spreading process.
AB  - Recent studies have investigated the dendritic actin cytoskeleton of the cell
      edge's lamellipodial (LP) region by experimentally decreasing the activity of the
      actin filament nucleator and branch former, the Arp2/3 complex. Here we extend
      these studies via pharmacological inhibition of the Arp2/3 complex in sea urchin
      coelomocytes, cells that possess an unusually broad LP region and display
      correspondingly exaggerated centripetal flow. Using light and electron
      microscopy, we demonstrate that Arp2/3 complex inhibition via the drug CK666
      dramatically altered LP actin architecture, slowed centripetal flow, drove a
      lamellipodial-to-filopodial shape change in suspended cells, and induced a novel
      actin structural organization during cell spreading. A general feature of the
      CK666 phenotype in coelomocytes was transverse actin arcs, and arc generation was
      arrested by a formin inhibitor. We also demonstrate that CK666 treatment produces
      actin arcs in other cells with broad LP regions, namely fish keratocytes and
      Drosophila S2 cells. We hypothesize that the actin arcs made visible by Arp2/3
      complex inhibition in coelomocytes may represent an exaggerated manifestation of
      the elongate mother filaments that could possibly serve as the scaffold for the
      production of the dendritic actin network. 

PMID- 25568344
TI  - GPCR-mediated PLCbetagamma/PKCbeta/PKD signaling pathway regulates the cofilin
      phosphatase slingshot 2 in neutrophil chemotaxis.
AB  - Chemotaxis requires precisely coordinated polymerization and depolymerization of
      the actin cytoskeleton at leading fronts of migrating cells. However, GPCR
      activation-controlled F-actin depolymerization remains largely elusive. Here, we
      reveal a novel signaling pathway, including Galphai, PLC, PKCbeta, protein kinase
      D (PKD), and SSH2, in control of cofilin phosphorylation and actin cytoskeletal
      reorganization, which is essential for neutrophil chemotaxis. We show that PKD is
      essential for neutrophil chemotaxis and that GPCR-mediated PKD activation depends
      on PLC/PKC signaling. More importantly, we discover that GPCR activation
      recruits/activates PLCgamma2 in a PI3K-dependent manner. We further verify that
      PKCbeta specifically interacts with PKD1 and is required for chemotaxis. Finally,
      we identify slingshot 2 (SSH2), a phosphatase of cofilin (actin depolymerization
      factor), as a target of PKD1 that regulates cofilin phosphorylation and
      remodeling of the actin cytoskeleton during neutrophil chemotaxis. 

PMID- 25568345
TI  - Adaptive evolution of signaling partners.
AB  - Proteins that interact coevolve their structures. When mutation disrupts the
      interaction, compensation by the partner occurs to restore interaction otherwise
      counterselection occurs. We show in this study how a destabilizing mutation in
      one protein is compensated by a stabilizing mutation in its protein partner and
      their coevolving path. The pathway in this case and likely a general principle of
      coevolution is that the compensatory change must tolerate both the original and
      derived structures with equivalence in function and activity. Evolution of the
      structure of signaling elements in a network is constrained by specific protein
      pair interactions, by requisite conformational changes, and by catalytic
      activity. The heterotrimeric G protein-coupled signaling is a paragon of this
      protein interaction/function complexity and our deep understanding of this
      pathway in diverse organisms lends itself to evolutionary study. Regulators of G
      protein Signaling (RGS) proteins accelerate the intrinsic GTP hydrolysis rate of
      the Galpha subunit of the heterotrimeric G protein complex. An important RGS
      contact site is a hydroxyl-bearing residue on the switch I region of Galpha
      subunits in animals and most plants, such as Arabidopsis. The exception is the
      grasses (e.g., rice, maize, sugarcane, millets); these plants have Galpha
      subunits that replaced the critical hydroxyl-bearing threonine with a
      destabilizing asparagine shown to disrupt interaction between Arabidopsis RGS
      protein (AtRGS1) and the grass Galpha subunit. With one known exception (Setaria
      italica), grasses do not encode RGS genes. One parsimonious deduction is that the
      RGS gene was lost in the ancestor to the grasses and then recently acquired
      horizontally in the lineage S. italica from a nongrass monocot. Like all
      investigated grasses, S. italica has the Galpha subunit with the destabilizing
      asparagine residue in the protein interface but, unlike other known grass
      genomes, still encodes an expressed RGS gene, SiRGS1. SiRGS1 accelerates GTP
      hydrolysis at similar concentration of both Galpha subunits containing either the
      stabilizing (AtGPA1) or destabilizing (RGA1) interface residue. SiRGS1 does not
      use the hydroxyl-bearing residue on Galpha to promote GAP activity and has a
      larger Galpha-interface pocket fitting to the destabilizing Galpha. These
      findings indicate that SiRGS1 adapted to a deleterious mutation on Galpha using
      existing polymorphism in the RGS protein population. 

PMID- 25568346
TI  - Rates of vaccine evolution show strong effects of latency: implications for
      varicella zoster virus epidemiology.
AB  - Varicella-zoster virus (VZV) causes chickenpox and shingles, and is found in
      human populations worldwide. The lack of temporal signal in the diversity of VZV
      makes substitution rate estimates unreliable, which is a barrier to understanding
      the context of its global spread. Here, we estimate rates of evolution by
      studying live attenuated vaccines, which evolved in 22 vaccinated patients for
      known periods of time, sometimes, but not always undergoing latency. We show that
      the attenuated virus evolves rapidly (~ 10(-6) substitutions/site/day), but that
      rates decrease dramatically when the virus undergoes latency. These data are best
      explained by a model in which viral populations evolve for around 13 days before
      becoming latent, but then undergo no replication during latency. This implies
      that rates of viral evolution will depend strongly on transmission patterns.
      Nevertheless, we show that implausibly long latency periods are required to date
      the most recent common ancestor of extant VZV to an "out-of-Africa" migration
      with humans, as has been previously suggested.

PMID- 25568348
TI  - Antigen-armed antibodies targeting B lymphoma cells effectively activate antigen
      specific CD4+ T cells.
AB  - The treatment of non-Hodgkin lymphomas has benefited enormously from the
      introduction of monoclonal antibody-based therapies. However, the efficacy of
      these treatments varies with lymphoma subtypes and typically decreases with
      subsequent relapses. Here, we report on antigen-armed antibodies (AgAbs) as a
      potential treatment of B-cell lymphoma. AgAbs include antigens from ubiquitous
      pathogens, such as Epstein-Barr virus (EBV), that persist in their host and
      elicit strong lifelong T-cell responses. They act as vectors by introducing
      antigen directly into tumor cells to induce an antigen-specific CD4(+) T-cell
      response against these cells. We have fused antibodies targeting human B-cell
      surface receptors (CD19-22) to immunodominant T-cell antigens from EBV proteins,
      including EBNA1, EBNA3B, and EBNA3C. Exposure of EBV-transformed B cells and of
      Burkitt lymphoma cells to AgAbs led to antigen presentation, T-cell recognition,
      and target cell killing. The efficiency of AgAb action paralleled the abundance
      of the targeted molecules on lymphoma cells as well as their HLA class II
      expression levels. AgAbs can also induce activation and proliferation of EBV
      specific memory CD4(+) T cells ex vivo. These studies show the potential of AgAbs
      as an effective therapeutic strategy against B-cell lymphomas. 

PMID- 25568347
TI  - R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell
      transplant for newly diagnosed primary CNS lymphoma.
AB  - High-dose methotrexate-based chemotherapy is the mainstay of treatment of primary
      central nervous system lymphoma (PCNSL), but relapses remain frequent. High-dose
      chemotherapy (HDC) with autologous stem-cell transplant (ASCT) may provide an
      alternative to address chemoresistance and overcome the blood-brain barrier. In
      this single-center phase-2 study, newly diagnosed PCNSL patients received 5 to 7
      cycles of chemotherapy with rituximab, methotrexate (3.5 g/m(2)), procarbazine,
      and vincristine (R-MPV). Those with a complete or partial response proceeded with
      consolidation HDC with thiotepa, cyclophosphamide, and busulfan, followed by ASCT
      and no radiotherapy. Primary end point was 1-year progression-free survival
      (PFS), N = 32. Median age was 57, and median Karnofsky performance status 80.
      Following R-MPV, objective response rate was 97%, and 26 (81%) patients proceeded
      with HDC-ASCT. Among all patients, median PFS and overall survival (OS) were not
      reached (median follow-up: 45 months). Two-year PFS was 79% (95% confidence
      interval [CI], 58-90), with no events observed beyond 2 years. Two-year OS was
      81% (95% CI, 63-91). In transplanted patients, 2-year PFS and OS were 81%. There
      were 3 treatment-related deaths. Prospective neuropsychological evaluations
      suggested relatively stable cognitive functions posttransplant. In conclusion,
      this treatment was associated with excellent disease control and survival, an
      acceptable toxicity profile, and no evidence of neurotoxicity thus far. This
      trial was registered at www.clinicaltrials.gov as NCT00596154. 

PMID- 25568349
TI  - Acetylation of C/EBPepsilon is a prerequisite for terminal neutrophil
      differentiation.
AB  - C/EBPepsilon, a member of the CCAAT/enhancer binding protein (C/EBP) family of
      transcription factors, is exclusively expressed in myeloid cells and regulates
      transition from the promyelocytic stage to the myelocytic stage of neutrophil
      development, being indispensable for secondary and tertiary granule formation.
      Knowledge concerning the functional role of C/EBPepsilon posttranslational
      modifications is limited to studies concerning phosphorylation and sumoylation.
      In the current study, using ectopic expression and ex vivo differentiation of
      CD34(+) hematopoietic progenitor cells, we demonstrate that C/EBPepsilon is
      acetylated, which was confirmed by mass spectrometry analysis, identifying 4
      acetylated lysines in 3 distinct functional domains. Regulation of C/EBPepsilon
      acetylation levels by the p300 acetyltransferase and the sirtuin 1 deacetylase
      controls transcriptional activity, which can at least in part be explained by
      modulation of DNA binding. During neutrophil development, acetylation of lysines
      121 and 198 were found to be crucial for terminal neutrophil differentiation and
      the expression of neutrophil-specific granule proteins, including lactoferrin and
      collagenase. Taken together, our data illustrate a critical role for acetylation
      in the functional regulation of C/EBPepsilon activity during terminal neutrophil
      development. 

PMID- 25568350
TI  - AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without
      increasing thrombogenicity in hemophilia B dogs and mice.
AB  - Emerging successful clinical data on gene therapy using adeno-associated viral
      (AAV) vector for hemophilia B (HB) showed that the risk of cellular immune
      response to vector capsid is clearly dose dependent. To decrease the vector dose,
      we explored AAV-8 (1-3 * 10(12) vg/kg) encoding a hyperfunctional factor IX (FIX
      Padua, arginine 338 to leucine) in FIX inhibitor-prone HB dogs. Two naive HB dogs
      showed sustained expression of FIX-Padua with an 8- to 12-fold increased specific
      activity reaching 25% to 40% activity without antibody formation to FIX. A third
      dog with preexisting FIX inhibitors exhibited a transient anamnestic response (5
      Bethesda units) at 2 weeks after vector delivery following by spontaneous
      eradication of the antibody to FIX by day 70. In this dog, sustained FIX
      expression reached ~200% and 30% of activity and antigen levels, respectively.
      Immune tolerance was confirmed in all dogs after challenges with plasma-derived
      FIX concentrate. Shortening of the clotting times and lack of bleeding episodes
      support the phenotypic correction of the severe phenotype, with no clinical or
      laboratory evidence of risk of thrombosis. Provocative studies in mice showed
      that FIX-Padua exhibits similar immunogenicity and thrombogenicity compared with
      FIX wild type. Collectively, these data support the potential translation of gene
      based strategies using FIX-Padua for HB. 

PMID- 25568351
TI  - LMP1 mediates multinuclearity through downregulation of shelterin proteins and
      formation of telomeric aggregates.
AB  - Hodgkin lymphoma (HL) and Burkitt lymphoma are both germinal center-derived B
      cell lymphomas. To assess the consequences of permanent latent membrane protein 1
      (LMP1) expression as observed in tumor cells of Epstein-Barr virus (EBV) 
      associated HL, we analyzed 3-dimensional (3D) telomere dynamics and measured the
      expression of shelterin proteins at the transcriptional and translational level
      and their topographic distribution in the EBV-negative Burkitt cell line BJAB
      stably transfected with an inducible LMP1 system. Stable LMP1 expression led to a
      highly significant increase of multinucleated cells, nuclear volume, and 3D
      telomeric aggregates when compared with the LMP1-suppressed BJAB controls. Most
      importantly, LMP1 induced a significant downregulation of the shelterin
      components TRF1, TRF2, and POT1 at the transcriptional and translational level,
      and this downregulation was reversed after resuppression of LMP1. In addition, as
      revealed by spectral karyotyping, LMP1 induced "outre" giant cells and hypoploid
      "ghost" cells. This LMP1-induced multinucleation was blocked upon LMP1
      independent TRF2 expression. These results show that LMP1-dependent deregulation
      of telomere stability and nuclear organization via shelterin downregulation, in
      particular TRF2, favors chromosomal rearrangements. We speculate that telomeric
      aggregates and ongoing breakage-bridge-fusion cycles lead to disturbed
      cytokinesis and finally to multinuclearity, as observed in EBV-associated HL. 

PMID- 25568353
TI  - Polymorphisms in the 5'-flanking regions of the GH, PRL, and Pit-1 genes with
      Muscovy duck egg production.
AB  - Somatotropic axis-related genes contribute to reproduction of ducks. Five SNP in
      the 5'-flanking regions of the growth hormone (GH), prolactin (PRL), and
      pituitary-specific transcription factor (Pit-1) genes were identified and
      genotyped in a female population of Muscovy ducks. Association analysis of these
      SNP with Muscovy duck egg production traits was performed. Results showed that
      SNP C-515G of GH was significantly associated with egg number in ducks at age 59
      wk (E59W; P = 0.0009) and egg number in ducks at age 300 d (E300D; P = 0.0022).
      Single nucleotide polymorphism C-441T of GH was significantly associated with
      E59W (P = 0.0014). Significant associations of SNP T-884C and T-335C of PRL with
      the age at first egg (A1D), E59W, and E300D were detected in this population (P <
      0.0001). It was concluded that these 4 SNP might be useful markers to use with
      the aim of increasing Muscovy duck E59W. On the basis of genetic parameter
      estimation, the heritability of A1D, E300D, E59W, and molting time were 0.43 +/-
      0.04, 0.45 +/- 0.04, 0.36 +/- 0.04, and 0.04 +/- 0.03, respectively. Strong
      positive genetic correlation was noted between E59W and E300D (correlation
      coefficient = 0.80), whereas a negative association was noted between E59W and
      A1D (correlation coefficient = -0.80). Therefore, the selection for improved A1D
      should also increase E59W. 

PMID- 25568354
TI  - Maternal nutrition during pregnancy is associated with differential expression of
      imprinted genes and DNA methyltranfereases in muscle of beef cattle offspring.
AB  - Maternal diet during pregnancy is a major determinant of the fetal developmental
      competence and may induce long-lasting epigenetic changes to the offspring.
      Imprinted genes have important roles in fetal programming, growth, and
      development. There are, however, limited data available on the influence of
      maternal diet on the expression of imprinted genes in beef cattle. Therefore, the
      objective of this study was to analyze the impact of maternal diet during
      pregnancy on the expression of 5 imprinted genes and 3 DNA methyltransferase
      genes in longissimus dorsi muscle from Angus calves. A total of 36 Angus-cross
      cows were inseminated to a single sire and on Day 135 of gestation they were
      randomly assigned to either low-starch (haylage) or high-starch (corn silage)
      diets. Diets were initially formulated to provide isocaloric and isonitrogenous
      intake. The H19, MEG8, IGF2R, and DNMT3a genes showed differential expression in
      longissimus dorsi muscle in calves between the diet groups. Given that high
      starch diet is a source of energy for muscle growth and feed conversion
      efficiency in postnatal development, the mechanisms by which this diet affected
      expression of imprinted genes should be further explored. 

PMID- 25568355
TI  - Incidence of infection in 39-month-old ewes with TMEM154 diplotypes "1 1," "1 3,"
      and "3 3" after natural exposure to ovine progressive pneumonia virus.
AB  - Production and well-being of sheep and goats in many countries are harmfully
      impacted by small ruminant lentiviruses (SRLV) that cause incurable, progressive
      diseases. Susceptibility to ovine progressive pneumonia virus (OPPV), the North
      American form of SRLV, is influenced by variants of the ovine transmembrane
      protein 154 gene (TMEM154). The experimental objective was to estimate additive
      and dominance effects of TMEM154 haplotypes 1 and 3 on susceptibility of breeding
      ewes to infection after natural exposure to OPPV from birth to 39 mo of age.
      Sires and dams were heterozygous for TMEM154 haplotypes 1 and 3, producing ewe
      lambs with diplotypes "1 1," "1 3," and "3 3." These lambs were raised by mature,
      infected dams to ensure natural, maternal exposure to OPPV. Ewe lambs (n = 108)
      were kept for breeding and joined an infected flock of ewes to guarantee natural,
      nonmaternal exposure to OPPV. Ewes were bred to lamb at 1, 2, and 3 yr of age.
      Serum samples were collected at breeding, 1 mo before lambing and shortly after
      weaning each year to monitor infection status to 39 mo of age. During the
      experiment, 9 of the 108 ewes died while uninfected and data collected on these
      ewes were not analyzed. Infection status of the remaining 99 ewes at 39 mo of age
      was analyzed using logistic regression procedures. Effects of ewe type of birth,
      ewe type of rearing, and breed type of dam were not detected (P > 0.10), and the
      estimated sire variance component was nil. Ewe diplotype affected infection
      status (P < 0.0001), as did additive (P < 0.0001) and dominance (P < 0.0022)
      effects. Predicted probabilities of infection for ewes with diplotypes "1 1," "1
      3," and "3 3" were 0.10, 0.88, and 0.89, respectively, and confidence intervals
      for diplotypes "1 3" and "3 3" were distinct from "1 1." Haplotype 3 was
      completely dominant to haplotype 1 at 39 mo of age. The probability of infection
      for ewes with either diplotype "1 3" or "3 3" averaged 8.5 times that of ewes
      with diplotype "1 1." Diplotype "1 3" and "3 3" ewes were highly susceptible to
      nonmaternal transmission of OPPV, in contrast to diplotype "1 1" ewes. Therefore,
      the distribution of ewes with diplotypes "1 1," "1 3," and "3 3" within a flock
      will influence the number of infections caused by each route of transmission.
      Selection and mating strategies can be implemented to produce sheep that are
      genetically less susceptible to OPPV infection. 

PMID- 25568352
TI  - Polycomb genes, miRNA, and their deregulation in B-cell malignancies.
AB  - Posttranslational modifications of histone proteins represent a fundamental means
      to define distinctive epigenetic states and regulate gene expression during
      development and differentiation. Aberrations in various chromatin-modulation
      pathways are commonly used by tumors to initiate and maintain oncogenesis,
      including lymphomagenesis. Recently, increasing evidence has demonstrated that
      polycomb group (PcG) proteins, a subset of histone-modifying enzymes known to be
      crucial for B-cell maturation and differentiation, play a central role in
      malignant transformation of B cells. PcG hyperactivity in B-cell lymphomas is
      caused by overexpression or recurrent mutations of PcG genes and deregulation of
      microRNAs (miRNAs) or transcription factors such as c-MYC, which regulate PcG
      expression. Interplays of PcG and miRNA deregulations often establish a vicious
      signal-amplification loop in lymphoma associated with adverse clinical outcomes.
      Importantly, aberrant enzymatic activities associated with polycomb deregulation,
      notably those caused by EZH2 gain-of-function mutations, have provided a
      rationale for developing small-molecule inhibitors as novel therapies. In this
      review, we summarize our current understanding of PcG-mediated gene silencing,
      interplays of PcG with other epigenetic regulators such as miRNAs during B-cell
      differentiation and lymphomagenesis, and recent advancements in targeted
      strategies against PcG as promising therapeutics for B-cell malignancies. 

PMID- 25568356
TI  - Estimation of breed-specific heterosis effects for birth, weaning, and yearling
      weight in cattle.
AB  - Heterosis, assumed proportional to expected breed heterozygosity, was calculated
      for 6834 individuals with birth, weaning and yearling weight records from Cycle
      VII and advanced generations of the U.S. Meat Animal Research Center (USMARC)
      Germplasm Evaluation (GPE) project. Breeds represented in these data included:
      Angus, Hereford, Red Angus, Charolais, Gelbvieh, Simmental, Limousin and
      Composite MARC III. Heterosis was further estimated by proportions of British *
      British (B * B), British * Continental (B * C) and Continental * Continental (C *
      C) crosses and by breed-specific combinations. Model 1 fitted fixed covariates
      for heterosis within biological types while Model 2 fitted random breed-specific
      combinations nested within the fixed biological type covariates. Direct
      heritability estimates (SE) for birth, weaning ,and yearling weight for Model 1
      were 0.42 (0.04), 0.22 (0.03), and 0.39 (0.05), respectively. The direct
      heritability estimates (SE) of birth, weaning, and yearling weight for Model 2
      were the same as Model 1, except yearling weight heritability was 0.38 (0.05).
      The B * B, B * C, and C * C heterosis estimates for birth weight were 0.47
      (0.37), 0.75 (0.32), and 0.73 (0.54) kg, respectively. The B * B, B * C, and C *
      C heterosis estimates for weaning weight were 6.43 (1.80), 8.65 (1.54), and 5.86
      (2.57) kg, respectively. Yearling weight estimates for B * B, B * C, and C * C
      heterosis were 17.59(3.06), 13.88 (2.63), and 9.12 (4.34) kg, respectively.
      Differences did exist among estimates of breed-specific heterosis for weaning and
      yearling weight, although the variance component associated with breed-specific
      heterosis was not significant. These results illustrate that there are
      differences in breed-specific heterosis and exploiting these differences can lead
      to varying levels of heterosis among mating plans. 

PMID- 25568357
TI  - Inheritance of skeletal deformities in gilthead seabream (Sparus aurata) - lack
      of operculum, lordosis, vertebral fusion and LSK complex.
AB  - Morphological abnormalities in farmed gilthead seabream (Sparus aurata) are a
      major problem as it entails significant economic losses. In this study, 3 large
      scale experiments under different conditions of spawning, offspring handling and
      breeders phenotype were performed to analyze the inheritance of 4 types of
      deformities in this species: lack of operculum, lordosis, vertebral fusion, which
      are 3 of the most important skeletal deformities, and LSK, which is a consecutive
      repetition of lordosis/scoliosis/kyphosis. In Exp. [1] (mass spawning and
      fingerling sorting), 900 fish were analyzed at 509 d post-hatching: 846 fish that
      had been on-grown in a farm and 54 LSK-deformed fish that had been reared
      separately after being selected during the fingerling sorting process. A total of
      89 families were represented. A statistically significant association between 5
      of these families (from 6 breeders) and LSK-deformed fish was found. In Exp. [2]
      (mass spawning and no fingerling sorting), 810 fish were analyzed at 2 ages: 179
      and 689 d post-hatching. Significant relationships between 2 of the breeders and
      2 of the families with the lack of operculum prevalence of their descendants were
      found at 689 d but not at 179 d. Heritabilities: 0.09 +/- 0.09 at 179 d and 0.17
      +/- 0.08 at 689 d. Column deformities prevalence was low and no association with
      family was observed. Family relationships were determined by microsatellites
      multiplex PCR in both experiments. In Exp. [3] (designed mating), sires suffering
      from lordosis or lack of operculum or vertebral fusion deformities were mated
      with non-deformed dams and a mass-spawning mating was considered as a control.
      After analyzing 11,503 offspring at 159 d post-hatching, a significant
      relationship between each deformity prevalence and the mating of breeders
      suffering from the same deformity was observed. In addition, a significant
      prevalence of lack of operculum in offspring from lordotic matings was observed.
      Heritabilities ranged from 0.34 to 0.46 for the 3 deformities. The results of the
      present study suggest that these deformities have a genetic origin. They also
      suggest that the sorting process is not recommended and that producers should
      consider these deformities in genetic breeding programs to significantly improve
      their fish morphological quality and to minimize farmed fish deformities
      incidence. 

PMID- 25568358
TI  - Effects of in utero heat stress on postnatal body composition in pigs: I. Growing
      phase.
AB  - Environmentally induced heat stress (HS) negatively influences production
      variables in agriculturally important species. However, the extent to which HS
      experienced in utero affects nutrient partitioning during the rapid lean tissue
      accretion phase of postnatal growth is unknown. Study objectives were to compare
      future whole-body tissue accretion rates in pigs exposed to differing in utero
      and postnatal thermal environments when lean tissue deposition is likely
      maximized. Pregnant sows were exposed to thermoneutral (TN; cyclical 15 degrees C
      nighttime and 22 degrees C daytime; n = 9) or HS (cyclical 27 degrees C nighttime
      and 37 degrees C daytime; n = 12) conditions during their entire gestation.
      Twenty-four offspring from in utero TN (IUTN; n = 6 gilts and 6 barrows; 30.8 +/-
      0.2 kg BW) and in utero HS (IUHS; n = 6 gilts and 6 barrows; 30.3 +/- 0.2 kg BW)
      were euthanized as an initial slaughter group (ISG). Following the ISG, 48 pigs
      from IUTN (n = 12 gilts and 12 barrows; 34.1 +/- 0.5 kg BW) and IUHS (n = 12
      gilts and 12 barrows; 33.3 +/- 0.3 kg BW) were exposed to constant HS (34.1 +/-
      2.4 degrees C) or TN (21.5 +/- 2.0 degrees C) conditions until they reached 61.5
      +/- 0.8 kg BW, at which point they were sacrificed and their whole-body
      composition was determined. Homogenized carcasses were analyzed for N, crude fat,
      ash, water, and GE content. Data were analyzed using PROC MIXED in SAS 9.3.
      Rectal temperature and respiration rate increased (P < 0.01) during postnatal HS
      compared to TN (39.4 vs. 39.0 degrees C and 94 vs. 49 breaths per minute,
      respectively). Regardless of in utero environment, postnatal HS reduced (P <
      0.01) feed intake (2.06 vs. 2.37 kg/d) and ADG (0.86 vs. 0.98 kg/d) compared to
      TN conditions. Postnatal HS did not alter water, protein, and ash accretion rates
      but reduced lipid accretion rates (198 vs. 232 g/d; P < 0.04) compared to TN
      reared pigs. In utero environment had no effect on future tissue deposition
      rates; however, IUHS pigs from the ISG had reduced liver weight (P < 0.04; 17.9%)
      compared to IUTN controls. In summary, postnatal HS reduced adipose tissue
      accretion rates, but IUHS did not appear to impact either lean or adipose tissue
      accretion during this specific growth phase. 

PMID- 25568359
TI  - Effects of in utero heat stress on postnatal body composition in pigs: II.
      Finishing phase.
AB  - The detrimental effects of heat stress (HS) on animal productivity have been well
      documented. However, whether in utero HS interacts with a future thermal insult
      to alter tissue deposition during the finishing phase of pig growth is unknown.
      Study objectives were to compare the subsequent rate and quantity of whole-body
      tissue accretion in pigs exposed to differing in utero and postnatal thermal
      environments. Pregnant sows were exposed to thermoneutral (TN; cyclical 15
      degrees C nighttime and 22 degrees C daytime; n = 9) or HS (cyclical 27 degrees C
      nighttime and 37 degrees C daytime; n = 11) conditions during their entire
      gestation. Twenty-four offspring from in utero TN (IUTN; n = 6 gilts and 6
      barrows; 62.4 +/- 0.7 kg BW) and in utero HS (IUHS; n = 6 gilts and 6 barrows;
      61.9 +/- 0.8 kg BW) were euthanized as part of an initial slaughter group (ISG).
      After the ISG, 48 pigs from IUTN (n = 12 gilts and 12 barrows; 66.1 +/- 1.0 kg
      BW) and IUHS (n = 12 gilts and 12 barrows; 63.4 +/- 0.7 kg BW) were exposed to
      constant HS (34.4 +/- 1.8 degrees C) or TN (22.7 +/- 2.5 degrees C) conditions
      until they reached 80.5 +/- 1.5 kg BW, at which point they were sacrificed and
      their whole-body composition was determined. Homogenized carcasses were analyzed
      for N, crude fat, ash, water, and GE content. Data were analyzed using PROC MIXED
      in SAS 9.3. Rectal temperature and respiration rate increased during postnatal HS
      compared to TN (39.6 vs. 39.3 degrees C and 92 vs. 58 breaths per minute,
      respectively; P < 0.01). Postnatal HS decreased (P < 0.01) feed intake (2.13 vs.
      2.65 kg/d) and ADG (0.70 vs. 0.94 kg/d) compared to TN conditions, but neither
      variable was influenced by in utero environment. Whole-body protein and lipid
      accretion rates were reduced in HS pigs compared to TN controls (126 vs. 164 g/d
      and 218 vs. 294 g/d, respectively; P < 0.04). Independent of postnatal
      environments, IUHS reduced future protein accretion rates (16%; P < 0.01) and
      tended to increase lipid accretion rates (292 vs. 220 g/d; P < 0.07) compared to
      IUTN controls. The ratio of lipid to protein accretion rates increased (95%; P <
      0.01) in IUHS pigs compared to IUTN controls. In summary, the future hierarchy of
      tissue accretion is altered by IUHS, and this modified nutrient partitioning
      favors adipose deposition at the expense of skeletal muscle during this specific
      phase of growth. 

PMID- 25568360
TI  - Associations of conformation and locomotive characteristics in growing gilts with
      osteochondrosis at slaughter.
AB  - Osteochondrosis (OC) and abnormalities in conformation and locomotive
      characteristics (CLC) have been associated with premature culling in sows.
      Several CLC have been suggested to be associated with OC and might help as an in
      vivo indicator for and increased risk of having OC. The aim of this study was to
      investigate associations of OC with CLC assessed at several ages in growing gilts
      from 2 separate experiments over the effects of dietary restriction (Exp. 1) and
      floor type (Exp. 2) on OC prevalence. In Exp. 1, gilts (n = 211) were
      subjectively assessed for CLC at, on average, 4, 9, 11, 16, and 24 wk of age. In
      Exp. 2, gilts (n = 212) were subjectively assessed for CLC at, on average, 4, 9,
      11, 16, and 22 wk of age. Assessment was done on 10 conformation and 2 locomotive
      characteristics using a 9-point grading scale by 2 observers. At, on average, 27
      wk of age in Exp. 1 and 24 wk of age in Exp. 2, gilts were slaughtered and the
      knee, elbow, and hock joints were macroscopically assessed for OC. The CLC most
      frequently associated with OC were O shape or X shape of the hind legs, straight
      or bowed hind legs, and straight or sickled hock. X-shaped hind legs were
      associated with OC at slaughter in the knee joint at 4, 9, and 24 wk of age and
      at the animal level (all joints taken together) at 4, 9, and 16 wk of age.
      Straight or bowed hind legs were associated with OC at slaughter in the knee
      joint at 4 and 11 wk of age; in the hock joint at 11 wk of age; and at the animal
      level at 4, 9, 11, and 22 wk of age. Straight or sickled hock was associated with
      OC at slaughter in the knee joint at 4 wk of age, in the hock joint at 9 and 22
      wk of age, and at the animal level at 9 and 22 wk of age. Results show that
      several CLC assessed at several ages were associated with OC, but consistent
      associations of a type of CLC in every assessment could not be found. The
      associations of CLC with OC are, therefore, difficult to be used as an in vivo
      indicator of increased risk for OC. 

PMID- 25568361
TI  - Pertinent plasma indicators of the ability of chickens to synthesize and store
      lipids.
AB  - Excessive deposition of body fat is detrimental to production efficiency. The aim
      of this study was to provide plasma indicators of chickens' ability to store fat.
      From 3 to 9 wk of age, chickens from 2 experimental lines exhibiting a 2.5-fold
      difference in abdominal fat content and fed experimental diets with contrasted
      feed energy sources were compared. The diets contained 80 vs. 20 g of lipids and
      379 vs. 514 g of starch per kg of feed, respectively, but had the same ME and
      total protein contents. Cellulose was used to dilute energy in the high-fat diet.
      At 9 wk of age, the body composition was analyzed and blood samples were
      collected. A metabolome-wide approach based on proton nuclear magnetic resonance
      spectroscopy was associated with conventional measurements of plasma parameters.
      A metabolomics approach showed that betaine, glutamine, and histidine were the
      most discriminating metabolites between groups. Betaine, uric acid,
      triglycerides, and phospholipids were positively correlated (r > 0.3; P < 0.05)
      and glutamine, histidine, triiodothyronine, homocysteine, and beta
      hydroxybutyrate were negatively correlated (r < -0.3; P < 0.05) with relative
      weight of abdominal fat and/or fat situated at the top of external face of the
      thigh. The combination of plasma free fatty acids, total cholesterol,
      phospholipid, beta-hydroxybutyrate, glutamine, and methionine levels accounted
      for 74% of the variability of the relative weight of abdominal fat. On the other
      hand, the combination of plasma triglyceride and homocysteine levels accounted
      for 37% of the variability of fat situated at the top of external face of the
      thigh. The variations in plasma levels of betaine, homocysteine, uric acid,
      glutamine, and histidine suggest the implication of methyl donors in the control
      of hepatic lipid synthesis and illustrate the interplay between AA, glucose, and
      lipid metabolisms in growing chickens. 

PMID- 25568362
TI  - A polymorphism in myostatin influences puberty but not fertility in beef heifers,
      whereas u-calpain affects first calf birth weight.
AB  - The use of genetic markers to aid in selection decisions to improve carcass and
      growth characteristics is of great interest to the beef industry. However, it is
      important to examine potential antagonistic interactions with fertility in cows
      before widespread application of marker-assisted selection. The objective of the
      current experiment was to examine the influence of 2 commercially available
      markers currently in use for improving carcass traits, the myostatin (MSTN) F94L
      and MU-calpain (CAPN1) 316 and 4751 polymorphisms, on heifer development and
      reproductive performance. In Exp. 1, beef heifers (n = 146) were evaluated for
      growth and reproductive traits over a 3-yr period to determine if these
      polymorphisms influenced reproductive performance. In Exp. 2, heifers
      representing the 2 homozygous genotypes for the MSTN F94L polymorphism were
      slaughtered on d 4 of the estrous cycle and reproductive tracts were collected
      for morphological examination. In Exp. 1, there was a tendency (P = 0.06) for
      birth BW to be affected by MSTN with the Leu allele increasing birth BW in an
      additive fashion. Additionally, MSTN significantly affected the proportion of
      pubertal heifers by the start of the breeding season (P < 0.05) with the Leu
      allele additively decreasing the proportion pubertal; however, this did not
      result in a delay in conception or a decrease in pregnancy rates during the first
      breeding season (P > 0.15). The GT haplotype of CAPN1, which was previously
      associated with decreased meat tenderness, was associated with an additive
      decrease in birth BW of the first calf born to these heifers (P < 0.05). In Exp.
      2, there were no differences between the MSTN genotypes for gross or histological
      morphology of the anterior pituitary, uterus, or ovaries (P > 0.05). From these
      results, we concluded that the MSTN F94L and CAPN1 polymorphisms can be used to
      improve carcass traits without compromising fertility in beef heifers. The
      influence of these markers on cow performance and herd life remains to be
      determined. While the delay in puberty associated with the MSTN F94L polymorphism
      did not negatively impact reproductive performance in heifers, caution should be
      used when combining this marker with other markers for growth or carcass traits
      until the potential interactions are more clearly understood. 

PMID- 25568364
TI  - Estimation of calcium and phosphorus content in growing and finishing pigs: whole
      empty body components and relative accretion rates.
AB  - Two comparative serial-slaughter experiments were conducted to determine whole
      empty body (WEB) composition and accretion rates of Ca and P in 18 to 109 kg BW
      pigs to provide information for modeling of these nutrients for growth. Both
      studies were conducted with 5 sets of 5 littermate barrows which were allotted to
      5 slaughter groups in each study (Exp. 1: 18, 27, 36, 45, and 54 kg BW; Exp. 2:
      36, 54, 73, 91, and 109 kg BW). Pigs were fed corn-soybean meal-based diets
      fortified with minerals and vitamins in 2 dietary phases in Exp. 1 (Phase 1: 18
      to 36 kg BW; Phase 2: 36 to 54 kg BW) and 3 dietary phases in Exp. 2 (Phase 2: 36
      to 54 kg BW; Phase 3: 54 to 78 kg BW; and Phase 4: 78 to 109 kg BW). At the
      predetermined BW, pigs were slaughtered and separated into body components of
      hair, hooves, blood, head, viscera, and carcass. The carcass was split along the
      dorsal midline and the left carcass side was ground for chemical analysis. Whole
      empty body weight averaged 93.6% and 94.0% of live BW in Exp. 1 and Exp. 2,
      respectively. As WEB weight increased in both experiments, the percentage carcass
      of the WEB linearly (P < 0.05) increased, the percentage viscera linearly (P <
      0.05) decreased, and the mass (g) of N, ash, Ca, and P in the WEB increased
      linearly (R(2) = 0.98). The concentration (g/kg) of P in the WEB of 18 to 54 kg
      pigs increased from 4.30 to 4.57 (linear; P < 0.05) and for Ca increased from
      5.13 to 5.66 (linear; P < 0.05). In Exp. 2, P concentration was not related to
      WEB weight and Ca concentration increased quadratically (P < 0.05). The relative
      accretion rate of N to P was 1.00 (R(2) = 0.99) in the pigs from 18 to 54 kg. In
      conclusion, these results indicate that compositional changes as BW increases are
      strongly related to P retention and that the quantification of WEB P and
      relationships of WEB P to other chemical components in the body may be useful for
      modeling purposes in growing and finishing pigs. 

PMID- 25568363
TI  - Effect of feeding peroxidized dried distillers grains with solubles to sows and
      progeny on growth performance and metabolic oxidative status of nursery pigs.
AB  - This experiment evaluated the effects of including peroxidized corn dried
      distillers grains with solubles (DDGS) in diets for sows and nursery pigs on
      growth performance, vitamin E (VE), and Se status, and the incidence of mulberry
      heart disease (MHD) of nursery pigs. Sows (n = 12) were fed corn-soybean meal
      diets (C-SBM) or C-SBM diets with DDGS (40% and 20% in gestation and lactation,
      respectively) for 3 parities. In the third parity, 108 weaned pigs (BW = 6.6 +/-
      0.36 kg) were blocked by BW within litter, assigned to pens (2 pigs/pen; 5 and 4
      pens per litter for groups 1 and 2, respectively), and pens were assigned 1 of 3
      nursery diets: 1) corn-soybean meal (CON), 2) 30% peroxidized DDGS (Ox-D), and 3)
      30% Ox-D with 5 * NRC (1998) level of VE (Ox-D+5VE) for 7 wk, in a 2 * 3
      factorial arrangement of sow and nursery diets (n = 9 pens/treatment). The
      peroxidized DDGS source in nursery diets contained concentrations of
      thiobarbituric acid reactive substances (TBARS) and peroxide values that were 25
      and 27 times greater than a reference corn sample. Sow colostrum, milk, and
      serum, as well as pig serum and liver samples, were analyzed for alpha-tocopherol
      and Se concentrations. Pig serum was analyzed for glutathione peroxidase activity
      (GPx), TBARS, and sulfur-containing AA (SAA). Pig hearts were evaluated for gross
      and histopathological lesions indicative of MHD, but none were detected. Pigs
      from sows fed DDGS tended to have reduced (P = 0.07) VE in serum during lactation
      and reduced VE at weaning (P < 0.01; 5.6 vs. 6.7 +/- 0.1 ug/mL) compared with
      pigs from sows fed C-SBM. Inclusion of DDGS in sow diets reduced the VE status of
      pigs during lactation, but not in the nursery when MHD can be a concern. Pigs fed
      Ox-D+5VE (P = 0.08) tended to have, and those fed Ox-D (P = 0.04) had greater
      ADFI than pigs fed CON, but ADG was not affected (P > 0.1) by nursery diet.
      Feeding Ox-D or Ox-D+5VE increased (P < 0.05) serum alpha-tocopherol compared
      with CON (2.5, 2.8, and 3.4 +/- 0.09 ug/mL, respectively), but TBARS and GPx were
      not affected by nursery diet. Serum concentration of SAA was 40% to 50% greater
      (P < 0.01) for pigs fed Ox-D or Ox-D+5VE compared with those fed C-SBM, which was
      likely due to greater (P < 0.01) SAA intake for pigs fed Ox-D. The antioxidant
      properties of SAA may have spared VE and Se and masked any effect of Ox-D on
      metabolic oxidation status. Therefore, increasing the dietary VE concentration
      was unnecessary in nursery diets containing Ox-D. 

PMID- 25568365
TI  - The efficacy of a new 6-phytase obtained from Buttiauxella spp. expressed in
      Trichoderma reesei on digestibility of amino acids, energy, and nutrients in pigs
      fed a diet based on corn, soybean meal, wheat middlings, and corn distillers'
      dried grains with solubles.
AB  - Sixteen cannulated pigs were used to evaluate the effect of a new 6-phytase
      derived from Buttiauxella spp. and expressed in Trichoderma reesei on apparent
      ileal digestibility (AID) of AA and apparent total tract digestibility (ATTD) of
      DM, N, Ca, P, Na, Mg, K, Cl, and energy. Pigs were fed 4 diets for 2 periods in a
      crossover design. Within each period, there were 4 blocks of 4 pigs per block
      with each diet represented within each block. The average initial BW in periods 1
      and 2 were 22 and 30 kg, respectively. Each period lasted 9 d with fecal
      collection on d 5 and 6 and a 12-h ileal digesta collection on d 7, 8, and 9.
      Pigs received a daily feed allowance of approximately 4.5% of their BW. The
      experimental diets were based on corn, soybean meal, wheat middlings, and corn
      distillers dried grain with solubles. Phytase was added at 0; 500; 1,000; or
      2,000 phytase units/kg of diet to a basal diet that contained 205, 15, 5.4, and
      10 g of CP, Lys, total P (1.6 g of nonphytate P), and Ca/kg diet, respectively.
      The addition of phytase improved (P < 0.05) AID of DM, N, Ca, and P. Increasing
      phytase supplementation linearly and quadratically increased (P < 0.05) AID of P
      and Ca, respectively, with AID of Ca showing a tendency for a linear increase (P
      = 0.053). Phytase supplementation of the basal diet improved (P < 0.05) AID of P
      from 46 to 62%. Phytase supplementation increased (P < 0.05) ATTD of DM, N, Ca,
      P, Mg, K, and energy. Contrasts showed that phytase supplementation of the basal
      diet increased (P < 0.05) AID for 8 indispensable AA (Arg, His, Ile, Leu, Lys,
      Phe, Thr, and Val), 6 dispensable AA (Ala, Asp, Cys, Glu, Ser, and Tyr), as well
      as for total AA. Furthermore, phytase supplementation to the basal diet showed a
      tendency (P < 0.10) to increase ileal digestibility of Gly. Ileal digestibility
      of Met, Trp, and Pro were not affected by phytase supplementation. Increasing the
      level of phytase supplementation resulted in linear increases (P < 0.05) in AID
      of 6 indispensable AA (Arg, Ile, Leu, Lys, Phe, and Val) and 1 dispensable AA
      (Asp) with 4 AA (His, Cys, Glu, and Tyr) showing a tendency for linear increase
      (P < 0.10) in AID of AA. The results from this study showed that in addition to
      increasing P and Ca utilization, the new Buttiauxella 6-phytase expressed in
      Trichoderma reesei enhanced ileal digestibility of N and several AA in growing
      pigs in a dose-dependent manner. 

PMID- 25568366
TI  - Copper bioavailability, blood parameters, and nutrient balance in mink.
AB  - A 3 * 3 + 1 factorial experiment was conducted based on a completely randomized
      design to evaluate the effects of different sources of copper on plasma
      metabolites, nutrient digestibility, relative copper bioavailability, and
      retention of some minerals in male mink. Animals in the control group were fed a
      basal diet, which mainly consisted of corn, fish meal, meat and bone meal, and
      soybean oil, with no copper supplementation. Mink in the other 9 treatments were
      fed the basal diet supplemented with Cu from reagent-grade copper sulfate
      (CuSO4), tribasic copper chloride (TBCC), or copper methionine (CuMet). Copper
      concentrations of the experimental diets were 50, 100, and 150 mg Cu/kg DM. Blood
      samples were collected via the toe clip at the end of study (d 42) to determine
      blood hematology and blood metabolites. A metabolism trial of 4 d was conducted
      during the last week of experimental feeding. There was a linear (P < 0.01)
      effect of dose of Cu on plasma Cu concentrations, ceruloplasmin concentration,
      and Cu-Zn superoxide dismutase activity. A linear response to Cu dose was noted
      for fat (P < 0.05) digestibility. Supplemental dose of Cu linearly increased (P <
      0.05) liver Cu and decreased (P < 0.05) liver Zn level but did not alter liver
      Fe. The concentration of liver Cu of the mink fed with TBCC and CuMet diets was
      greater (P < 0.05) than that fed CuSO4. Compared with CuSO4 (100%), relative
      bioavailability values of TBCC were 104 and 104%, based on serum ceruloplasmin
      and liver copper, respectively, and relative bioavailability values of CuMet were
      130 and 111%. CuMet and TBCC are more bioavailable than CuSO4. In conclusion, the
      relative bioavailability of CuMet obtained in this study was greater than that of
      CuSO4 and TBCC. Dose of Cu had an important effect on the regulating
      ceruloplasmin concentration, Cu-Zn superoxide dismutase activity, and the
      digestion of dietary fat in mink. 

PMID- 25568367
TI  - Effect of added zinc in diets with ractopamine hydrochloride on growth
      performance, carcass characteristics, and ileal mucosal inflammation mRNA
      expression of finishing pigs.
AB  - Two experiments were conducted to determine the effects of increasing the dietary
      Zn content on growth performance, carcass characteristics, plasma Zn, and ileal
      mucosal inflammation mRNA expression of finishing pigs fed diets containing
      ractopamine HCl (RAC; Elanco Animal Health, Greenfield, IN). In Exp. 1, 312 pigs
      (327 * 1050; PIC, Hendersonville, TN; 94 kg BW) were used in a 27-d study. There
      were 2 pigs per pen and 26 pens per treatment. Treatments included a corn-soybean
      meal diet (control; 0.66% standardized ileal digestible [SID] Lys); a diet (0.92%
      SID Lys) with 10 mg/kg RAC; and the RAC diet plus 50, 100, or 150 mg Zn/kg from
      ZnO or 50 mg Zn/kg from a Zn AA complex (ZnAA; Availa-Zn; Zinpro, Eden Prairie,
      MN). All diets also contained 83 mg Zn/kg from ZnSO4 in the trace mineral premix.
      Pigs fed the RAC diet without added Zn had increased (P < 0.05) ADG, G:F, HCW,
      carcass yield, and loin weight compared with pigs fed the control diet.
      Increasing Zn from ZnO in diets containing RAC tended to increase (linear, P =
      0.067) G:F and loin weight (quadratic, P = 0.064). Pigs fed diets with 50 mg
      Zn/kg from ZnAA tended to have increased (P = 0.057) ADG compared with pigs fed
      the RAC diet. In Exp. 2, 320 pigs (327 * 1050; PIC; 98 kg BW) were used in a 35-d
      study. There were 2 pigs per pen and 20 pens per treatment. Treatments included a
      control diet (0.66% SID Lys); a diet (0.92% SID Lys) with 10 mg/kg RAC; or the
      RAC diet plus 75, 150, and 225 mg Zn/kg from ZnO or ZnAA. All diets also
      contained 55 mg Zn/kg from ZnSO4 from the trace mineral premix. Pigs fed the RAC
      diet had increased (P < 0.05) ADG, G:F, HCW, loin depth, percentage lean, and
      liver weight compared with pigs fed the control diet. No Zn level or source
      effects or level * source interactions were observed for growth performance. A Zn
      level * source interaction (quadratic, P = 0.007) was observed in liver Zn
      concentrations. This resulted from liver Zn concentrations plateauing at 150 mg
      Zn/kg when ZnO was supplemented, while there was a linear increase when using
      ZnAA. Increasing Zn in diets containing RAC increased (linear, P < 0.05) plasma
      Zn on d 18 and 32. The expression of IL-1beta was increased (P = 0.014) in mucosa
      of pigs fed the RAC diet compared with those fed the control diet. Expression of
      IL-1beta decreased (linear, P = 0.026) in the mucosa of pigs fed increasing added
      Zn. In conclusion, adding Zn to diets containing RAC resulted in a trend for
      improved growth performance of pigs in 1 of 2 experiments. Also, additional Zn
      increased plasma Zn and reduced IL-1beta. 

PMID- 25568368
TI  - Methane digester effluent from swine excreta as a nutrient and water source for
      growing and finishing swine.
AB  - The experimental objective was to evaluate swine methane digester effluent (SMDE)
      as a water and nutrient source for swine. The mesophilic methane digester was
      loaded daily with manure from finishing swine fed a corn-soybean meal diet. Dry
      diet was mixed with SMDE (3.7% DM) and fed twice daily in troughs. Tap water was
      provided and consumption measured. Barrows were group fed (3 pigs/pen) and
      adapted to SMDE by increasing SMDE for 7 d, with the full amount fed from d 8 to
      the end of the feeding phase (d 21, 14, 23, or 37 for Exp. 1 to 4, respectively).
      Blood samples were collected on d 0, 10, 21, and 31 to determine plasma
      concentrations of glucose and plasma urea N (PUN). Barrows were placed in
      individual metabolism cages for a 5-d acclimation and a 5-d fecal and urine
      collection to determine apparent N and energy utilization. For Exp. 1, 18 pigs
      averaging 75 kg BW were allotted to diets with 0, 48.6, or 63.7% SMDE, as-fed
      basis. For Exp. 2 and 3, 12 pigs/experiment averaged 117 and 70 kg, respectively,
      and were allotted to diets with 0 or 63.7% SMDE, as-fed basis. At the end of Exp.
      2 and 3, pigs were sacrificed and liver samples were collected to determine urea
      cycle enzyme activity, and loin was saved for taste panel evaluation. For Exp. 4,
      pigs averaged 40 kg and were allotted to diets with 0 or 57.5% SMDE, as-fed
      basis. The ADFI, ADG, and G:F of finishing swine (Exp. 1 to 3) were not reduced
      by feeding diets containing 63.7% SMDE (as-fed basis), whereas ADG and G:F of
      growing swine (Exp. 4) were reduced (P < 0.01) by feeding a diet containing 57.5%
      SMDE. Pigs fed diets containing SMDE consumed 31 to 56% less (P < 0.05) water and
      had greater (P < 0.01) PUN concentrations than pigs fed control diets. Pigs fed
      diets containing SMDE excreted more (g, P < 0.05) fecal N and absorbed and
      retained less N (%; P < 0.01) and energy (DE and ME) than pigs fed control diets.
      Treatment had no effect on urea cycle enzyme activity. In conclusion, finishing
      swine adapted to diets containing 63.7% SMDE (as-fed basis) based on growth
      performance, whereas growing swine did not adapt to a diet containing 57.5% SMDE
      because of the large content of nonprotein N in SMDE. Recycling SMDE to swine
      greatly reduced fresh water consumption, whereas the protein and energy values of
      SMDE were approximately 0 for swine. Therefore, SMDE is more appropriately
      recycled as a source of water and N for ruminant nutrition or crop production. 

PMID- 25568369
TI  - True and standardized total tract phosphorus digestibility in canola meals from
      Brassica napus black and Brassica juncea yellow fed to growing pigs.
AB  - The aim was to determine the true total tract digestibility (TTTD) and
      standardized total tract digestibility (STTD) of P in canola meals from Brassica
      napus black (BNB) and Brassica juncea yellow (BJY) fed to growing pigs. Fifty
      four barrows with an initial BW of 19.9 +/- 0.22 kg (mean +/- SEM) were allocated
      in 3 consecutive blocks to 1 of 9 dietary treatments in a randomized complete
      block design to give 6 replicate pigs per diet. Dietary treatments were
      cornstarch based with increasing concentrations of P, that is, 0.8, 1.6, 2.4, and
      3.3 g/kg (as-fed basis) from either BNB or BJY as the sole source of P and a
      gelatin-based P-free diet. Limestone was added to maintain a Ca:total P ratio of
      1.2:1 in all diets. All diets contained titanium dioxide (3 g/kg) as an
      indigestible marker. Daily feed allowance was calculated to supply 2.6 times the
      maintenance energy requirement based on the BW at the beginning of each period
      and offered in 2 equal portions at 0800 and 1600 h as a dry mash. Pigs were
      individually housed in metabolism crates and fed experimental diets for 16 d,
      including 9 d for adaptation to feed and 5 d for total but separate collection of
      feces and urine. The apparent total tract digestibility values of P increased
      from 19.0 to 30.0% for BNB and from 17.3 to 28.3% for BJY as the dietary P
      content increased from 0.8 to 3.3 g/kg DM. The TTTD of P was determined using the
      regression analysis as dietary P content increased from 0.8 to 3.3 g/kg whereas
      the STTD of P was calculated for the diet with the highest P content (i.e., 3.3
      g/kg, as-fed basis) using the P-free diet to estimate endogenous P losses (EPL).
      The total and basal EPL estimates obtained with regression analysis and the P
      free diet were 665 +/- 0.03 and 209 +/- 96 mg/kg DMI, respectively. The TTTD of P
      was 33.3 and 32.0% in BNB and BJY, respectively. Respective STTD values were 31.0
      and 28.3%. The results indicated that the TTTD and STTD of P were comparable in
      the 2 canola meals from BNB and BJY canola. 

PMID- 25568370
TI  - Nutrient digestibility of solvent-extracted Brassica napus and Brassica juncea
      canola meals and their air-classified fractions fed to ileal-cannulated grower
      pigs.
AB  - Energy and nutrient digestibility of solvent-extracted canola meal (CM) is
      limited in pigs by its relatively high fiber content. The seed hull, which
      greatly contributes to the fiber content of CM, is denser than the oil-free
      cotyledon. By utilizing streams of air, air classification partially separates
      these seed components on the basis of their different sizes and densities to
      produce a low-fiber, light-particle fraction and a high-fiber, heavy-particle
      fraction. Compared with parent CM, ADF and NDF were reduced by 31.9% and 29.5% in
      the light-particle fraction and were enriched by 16.5% and 9.0% in the heavy
      particle fraction (DM basis), respectively. Particle size was 638, 18.9, and 76.1
      um for the parent CM and light- and heavy-particle fractions, respectively. To
      determine the nutrient digestibility of CM and their air-classified fractions,
      Brassica napus and B. juncea CM and their 2 air-classified fractions were
      evaluated in a 2 * 3 factorial arrangement together with a basal diet and an N
      free diet. The experiment was conducted as an 8 * 8 Latin square in which diets
      contained 40% B. napus or B. juncea CM or their air-classified fractions and 60%
      basal diet. Digesta data from pigs fed the N-free diet served to subtract basal
      endogenous AA losses. Eight ileal-cannulated barrows (32 kg initial BW) were fed
      the 8 diets at 2.7 times maintenance DE for eight 11-d periods. At the end of
      each period, feces were collected for 48 h, and ileal digesta were collected for
      two 12-h periods. The DE and calculated NE values and the apparent total tract
      digestibility (ATTD) of GE were 6.3%, 10.0%, and 7.8% greater (P < 0.001) for B.
      juncea CM than for B. napus CM; 6.1%, 10.8%, and 5.3% greater (P < 0.001) for the
      light-particle fraction than for parent CM; and 5.4%, 7.2%, and 3.8% lower (P <
      0.001) for the heavy-particle fraction than for parent CM, respectively. The
      standardized ileal digestibilities (SID) of His, Ile, Val, Asp, and Tyr were
      greater (P < 0.05) for B. juncea CM than for B. napus CM. The SID of CP and AA
      were greater (P < 0.01) in the light-particle fraction than in the heavy-particle
      fraction. The SID of Trp, Glu, Pro, and Tyr were greater (P < 0.05) in the light
      particle fraction than in parent CM. In conclusion, B. juncea CM had greater
      energy and AA digestibility than B. napus CM because of reduced fiber content.
      Air classification of CM increased its energy and AA digestibility in the light
      particle fraction for pigs because of the reduced dietary fiber content and
      decreased particle size. 

PMID- 25568371
TI  - The impact of dietary protein levels on nutrient digestibility and water and
      nitrogen balances in eventing horses.
AB  - This study was performed to evaluate the impact of dietary protein levels on
      nutrient digestibility and water and nitrogen balances in conditioning eventing
      horses. Twenty-four Brazilian Sport Horses, male and female (8.0 to 15.0 yr; 488
      +/- 32 kg BW), were used in a randomized design with 4 levels of CP diets: 7.5%,
      9.0%, 11.0%, and 13.0%. A digestion assay was performed with partial feces
      collection over 4 d, followed by 1 d of total urine collection. Data were
      submitted to regression analysis and adjusted to linear and quadratic models (P <
      0.05). No differences were observed in the intake of DM, OM, EE, ADF, and NDF as
      a function of dietary protein levels. Dry matter intake average was 1.7% of BW.
      CP and N intake showed a linear increase as a function of increasing protein
      level in diets. A quadratic response (P < 0.05) was observed on the CP and NDF
      digestibility coefficients, with the maximum estimated level of digestibility at
      11.6% and 11.4% CP in the diet, respectively. There was a linear effect on ADF
      digestibility coefficients, digestible DM and protein intake, and CP/DE ratio
      according to dietary protein levels. There was no impact of dietary protein
      levels on daily water intake, total water intake, or fecal water excretion.
      Urinary excretion values showed a linear increase in response to increased
      dietary protein levels, but no impact was observed on water balance, with an
      average of 8.4 L/d. Nitrogen intake (NI), N absorption (NA), and urinary N
      increased linearly as a function of increasing dietary protein levels. There was
      no impact of dietary protein levels on N retention (NR), with an average of 7.5 g
      N/d. Nitrogen retention as a percentage of NI or NA showed no significant changes
      in the function of dietary protein levels. There was an impact of dietary protein
      levels on the digestibility coefficient of CP, NDF, ADF, and digestible protein
      intake on conditioning eventing horses. The 11.6% CP level in the diet provided
      an intake of 2.25 g CP/kg BW and 0.37 g N/kg BW, and this intake was the most
      appropriate for the conditioning of intensely exercised horses, considering the
      responses related to NI, NA, and the estimated NR to NA ratio. The NDF and ADF
      responses indicated that dietary fiber was more digested with an increased amount
      of N in the digestive tract. 

PMID- 25568372
TI  - Dietary beta-galactomannans have beneficial effects on the intestinal morphology
      of chickens challenged with Salmonella enterica serovar Enteritidis.
AB  - Salmonella enterica serovar Enteritidis is one of the leading causes of food
      borne salmonellosis in humans. Poultry is the single largest reservoir, and the
      consumption of incorrectly processed chicken meat and egg products is the major
      source of infection. Since 2006, the use of antibiotics as growth promoters has
      been banned in the European Union, and the dietary inclusion of beta
      galactomannans (betaGM) has become a promising strategy to control and prevent
      intestinal infections. The aim of this study was to investigate the effect of
      various betaGM-rich products on intestinal morphology in chickens challenged with
      Salmonella Enteritidis. To assess this effect, a total of 280 male Ross 308
      chickens were studied (40 animals per treatment housed in 5 cages). There were 7
      treatments, including controls: uninoculated birds fed the basal diet (negative
      control) and inoculated birds fed the basal diet (positive control) or the basal
      diet supplemented with Salmosan (1 g/kg), Duraio gum (1 g/kg), Cassia gum (1
      g/kg), the cell walls of Saccharomyces cerevisiae (0.5 g/kg), or the antibiotic
      colistine (0.8 g/kg). The birds were fed these diets from the d 1 to 23, except
      the animals in the colistine group, which were fed the diet containing the
      antibiotic only from d 5 to 11. The inoculated animals were orally infected on d
      7 with 10(8) cfu of Salmonella Enteritidis. Bird performance per replicate was
      determined for the whole study period (23 d), and the distal ileum and cecal
      tonsil of 5 animals per treatment (1 animal per replicate) were observed at
      different magnification levels (scanning electron, light, and laser confocal
      microscopy). In the images corresponding to the treatments containing betaGM we
      observed more mucus, an effect that can be associated with the observation of
      more goblet cells. Moreover, the images also show fewer M cells, which are
      characteristic of infected animals. Regarding the morphometric parameters, the
      animals that received Duraio and Cassia gums show greater (P = 0.001 and P =
      0.016, respectively) villus length compared with the animals in the positive
      control, thus indicating the capacity of these products to increase epithelial
      surface area. However, no effect (P > 0.05) on microvillus dimensions was
      detected. In conclusion, the results obtained indicating the beneficial effects
      of these betaGM on intestinal morphology give more evidence of the positive
      effects of these supplements in poultry nutrition. 

PMID- 25568373
TI  - The impact of dietary fat withdrawal on carcass iodine value, belly
      characteristics, and changes in body fat over time.
AB  - The inclusion of unsaturated fats in pig diets has raised issues related to pork
      carcass fat quality. The objective of this experiment was to understand how
      withdrawal from the diet of unsaturated dietary fat before slaughter impacts the
      composition of jowl fat during the growth cycle and at market. Fifty individually
      housed pigs (PIC 337 * C22/29; initial BW = 59.3 +/- 0.55 kg) were allotted based
      on sex and initial BW to 10 treatments for an 82-d experiment as follows: 3
      dietary fat withdrawal times before slaughter (21, 42, or 63 d) by 3 dietary fat
      unsaturation loads (DFUL), which includea high intake of unsaturated fatty acids
      supplied through an inclusion of 5% corn oil (HIGH), a high intake of a mixture
      of saturated and unsaturated fatty acids supplied through an inclusion of 5%
      animal-vegetable blend (MED), and a moderate intake of unsaturated fatty acids
      supplied through an inclusion of 2.5% corn oil (LOW). Pigs were weighed and jowl
      adipose samples were collected on d 0, 21, 42, and 63 and at harvest on d 82.
      Data were analyzed using PROC MIXED with treatment and sex as fixed effects. At
      market (d 82), increasing the withdrawal of dietary fat further away from market
      increased 18:1 (P = 0.045) and tended to increase 14:0 concentrations (P =
      0.054). It also significantly decreased 18:2 (P < 0.001) and tended to decrease
      18:3 concentrations (P = 0.081). A HIGH DFUL resulted in the greatest 18:2
      concentrations in jowl fat followed by LOW; MED resulted in the lowest 18:2
      levels (P < 0.001). Dietary fat withdrawal before market significantly reduced
      carcass iodine value (IV) measured at d 82 (P = 0.006). In conclusion, elevated
      18:2 intake makes lowering carcass IV in the depot fat very difficult and may
      take as long as 61 d. The withdrawal of unsaturated dietary fat apparently
      altered the fat depot to be more reflective of fat synthesized de novo, resulting
      in a more saturated depot fat. Importantly, this alteration of deposited fat
      composition did not translate into improved belly firmness, depth, weight, or fat
      color. 

PMID- 25568374
TI  - Effects of adding supplemental tallow to diets containing distillers dried grains
      with solubles on fatty acid digestibility in growing pigs.
AB  - An experiment was conducted to measure the apparent ileal digestibility (AID) and
      apparent total tract digestibility (ATTD) of fatty acids in diets containing 0 or
      30% corn distillers dried grains with solubles (DDGS) and 0, 5, or 10% tallow.
      Barrows (n = 24; initial BW = 25 kg) were surgically fitted with a T-cannula at
      the distal ileum. Pigs (n = 4/diet) were randomly assigned to diets: corn-soybean
      meal control (CON), CON plus 5% tallow (5T0D), CON plus 10% tallow (10T0D), CON
      plus 30% DDGS (0T30D), CON plus 5% tallow and 30% DDGS (5T30D), and CON plus 10%
      tallow and 30% DDGS (10T30D). Eight replicates per treatment were achieved by
      randomizing diets among pigs for a second collection period. Each pig was fed
      their respective diet for a 5-d adaptation period followed by 3-d fecal
      collection and 2-d ileal digesta collection periods. The AID and ATTD of fatty
      acids was calculated using the index method and acid-insoluble ash as an
      indigestible marker. When tallow was added to diets with 0% DDGS, there was no
      effect on AID of palmitic acid (C16:0) or SFA, while AID of stearic acid (C18:0)
      was increased (66.87% for CON, 72.06% for 5T0D, and 76.81% for 10T0D; P < 0.01).
      However, when diets contained 30% DDGS, the AID of all SFA was reduced as levels
      of tallow increased C16:0 (77.62% for 0T30D, 69.66% for 5T30D, and 68.43% for
      10T30D), C18:0 (85.87% for 0T30D, 64.08% for 5T30D, and 61.25% for 10T30D), and
      SFA (79.88% for 0T30D, 68.23% for 5T30D, and 66.29% for 10T30D). The AID of MUFA
      was not affected when tallow was added to diets with 30% DDGS but actually
      increased in 5T0D and 10T0D. The amount of apparent ileal digested fatty acids
      increased with the addition of DDGS and tallow regardless of their digestibility.
      Amounts of ileal digested MUFA and PUFA increased when both DDGS (P < 0.01) and
      tallow (P < 0.01) were included in the diet compared to when either ingredient
      was excluded. For ileal digestible SFA, an interaction (P < 0.01) between DDGS
      and tallow was observed. Interactions between DDGS and tallow were observed for
      ATTD of all fatty acids (P < 0.01), except for linoleic acid and PUFA, which were
      not affected by dietary treatment. The amount of ileal digestible PUFA increased
      with tallow addition independent from the inclusion level of DDGS and it was a
      function the dietary concentration of the fatty acid. Adding tallow to corn
      soybean based diets increased the amount of digested SFA, but in diets with DDGS,
      the increment in amount of ileal digestible SFA was less prominent due to lesser
      digestibility of SFA. 

PMID- 25568375
TI  - Effects of adding supplemental tallow to diets containing 30% distillers dried
      grains with solubles on growth performance, carcass characteristics, and pork fat
      quality in growing-finishing pigs.
AB  - Crossbred pigs (n = 315) were blocked by initial BW (6.8 +/- 1.1 kg) and randomly
      assigned to 1 of 4 dietary treatments to evaluate the effects of dietary
      inclusion of tallow and corn distillers dried grains with solubles (DDGS) on pig
      growth, carcass traits, and pork fat quality. Diets consisted of a corn-soybean
      meal control diet (CON) and another 3 corn-soybean meal diets containing 5%
      tallow (T), 30% DDGS (D), or 5% tallow plus 30% DDGS (TD) in a 2 * 2 factorial
      arrangement of treatments. Diets were formulated to contain similar levels of
      available P and standardized ileal digestible Lys:ME among treatments. Pigs were
      housed in 40 pens, with 7 to 8 pigs per pen, to provide 10 replicates per
      treatment. Overall ADG did not differ among treatments. Compared with CON (2.76
      kg/d) and T (2.59 kg/d), feeding 30% DDGS reduced the ADFI (interaction, P >
      0.05) of pigs when fed with 5% tallow (2.45 kg/d for TD) but not when fed alone
      (2.76 kg/d for D). There was no effect of DDGS on overall G:F, but pigs fed diets
      with tallow had greater (P < 0.01) G:F (0.4) than pigs fed no tallow (0.37).
      Feeding tallow increased (P < 0.01) HCW, carcass yield, and backfat depth of pigs
      independent of DDGS. Feeding DDGS reduced (P < 0.01) belly firmness, as measured
      by belly flop angle, independent of tallow (D = 71.8 degrees  and TD = 57.7
      degrees  vs. CON = 134.0 degrees  and T = 113.4 degrees ) and tallow also tended
      to reduce belly firmness (P < 0.10). Feeding DDGS and tallow reduced the
      concentration of SFA in belly fat, while the concentration of MUFA were increased
      (P < 0.01) by feeding tallow but not DDGS. Conversely, feeding DDGS increased (P
      < 0.01) the concentration of PUFA in belly fat but there was no effect of tallow.
      An interaction (P = 0.03) between DDGS and tallow for iodine value (IV) of belly
      fat was observed, in which addition of tallow or DDGS increased the IV of belly
      fat (64.22 for T and 71.22 for D vs. 59.01 for CON) but addition of both reduced
      IV (67.88 for TD). The IV of belly fat and backfat were correlated (P < 0.01)
      with the IV product of the diet fed in phase 3 (r = 0.49 and r = 0.81,
      respectively). In conclusion, adding 5% tallow to 30% DDGS diets improved G:F and
      carcass yield while reducing the IV of belly fat. However, pork fat firmness as
      measured by belly flop angle was not improved. 

PMID- 25568376
TI  - Spray-dried plasma promotes growth, modulates the activity of antioxidant
      defenses, and enhances the immune status of gilthead sea bream (Sparus aurata)
      fingerlings.
AB  - Terrestrial animal byproduct meals, including nonruminant blood meal and blood
      products, represent the largest and largely untapped safe source of animal
      protein available within the international market for the aquafeed industry.
      Spray-dried blood and spray-dried plasma (SDP) proteins have long been recognized
      as high-quality feed ingredients for farmed animals. In this study, we evaluated
      the inclusion of SDP from porcine blood (SDPP) in growing diets for gilthead sea
      bream. Three isonitrogenous (CP = 51.2%) and isolipidic (fat = 12.4%) diets
      manufactured by cold extrusion (0.8 to 1.5 mm pellet size) were prepared by
      substituting high-quality fish meal with 0, 3, and 6% SDPP. The diets were tested
      for a period of 60 d at 22 degrees C with 4 replicates each (400-L
      cylindroconical tanks, 150 fish per tank, and initial density = 0.5 kg/m(3)). The
      SDPP inclusion in diets for gilthead sea bream fingerlings were evaluated in
      terms of growth performance, feed utilization, histological organization of the
      intestinal mucosa, activity of oxidative stress enzymes (catalase, glutathione S
      transferase, glutathione peroxidase, and glutathione reductase) in the intestine,
      and nonspecific serum immune parameters (lysozyme and bactericidal activity).
      Results from this study indicated that dietary SDPP promoted fish growth in terms
      of BW and length; fish fed 3% SDPP were 10.5% heavier (P < 0.05) than those fed
      the control diet. Spray-dried plasma from porcine blood modulated the activity of
      the antioxidative defenses in the intestine (P < 0.05) and increased the density
      of goblet cells in the intestine (P < 0.05) and benefited the host by providing
      an effective immune barrier against gut pathogenic microbiota. The nonspecific
      serum immune response in fish fed diets with SDPP was greater (P < 0.05) than in
      fish fed the control diet. These results indicated that the inclusion of SDPP in
      gilthead sea bream feed could be beneficial for the fish by enhancing intestinal
      and serum innate immune function and the activity of antioxidative stress enzymes
      of the intestine and promoting growth performance. 

PMID- 25568377
TI  - Continual feeding of two types of microalgal biomass affected protein digestion
      and metabolism in laying hens.
AB  - A 14-wk study was conducted to determine the nutritional efficacy and ssmetabolic
      impact of 2 types of microalgal biomass as alternative protein sources in laying
      hen diets. Shaver hens (total = 150 and 26 wk old) were fed 1 of 5 diets: a
      control or a defatted green microalgal biomass (DG; Desmodesmus spp.) at 25% and
      a full-fatted diatom biomass (FD; Staurosira spp.) at 11.7% inclusion with or
      without protease. This experiment consisted of 5 replicates per treatment and
      each replicate contained 6 hens individually reared in cages (1 hen for
      biochemical data/replicate). Despite decreased ADFI (P = 0.03), hens fed DG or FD
      had final BW, overall hen-day egg production, and egg quality similar to the
      controls. Feeding DG or FD did not alter plasma concentrations of insulin,
      glutamine, and uric acid or alkaline phosphatase activity at wk 8 or 14 but
      decreased plasma 3-methyhistine concentrations (P = 0.03) and tartrate-resistant
      acid phosphatase (TRAP) activities (P < 0.001) at wk 14 and improved (P = 0.002)
      ileal total AA digestibility. Although DG or FD exhibited moderate effects on
      intestinal brush border protease activities and mRNA levels of duodenal
      transporters Pept1, Lat1, and Cat1, both substantially enhanced (P < 0.05)
      phosphorylation of hepatic protein synthesis key regulator S6 ribosomal protein
      (S6) and the ratio of phospho-S6 to S6 in the liver of hens. However, DG and FD
      manifested with different impacts on weights of egg and egg albumen, proteolytic
      activity of jejunal digesta, plasma TRAP activity, ileal total AA digestibility,
      and several intestinal genes and hepatic proteins. Supplemental protease in the
      DG and FD diets produced mixed effects on a number of measures. In conclusion,
      our findings revealed the feasibility of including greater levels of microalgal
      biomass as a source of feed protein for laying hens and a novel potential of the
      biomass in improving dietary protein digestion and body protein metabolism than
      previously perceived. 

PMID- 25568378
TI  - Spray-dried plasma attenuates inflammation and improves pregnancy rate of mated
      female mice.
AB  - Three studies were conducted to test the hypothesis that dietary spray-dried
      plasma (SDP) might improve pregnancy rate by ameliorating inflammation, using
      mice in an experimental model that produces a low pregnancy rate. Mated female
      mice (C57BL/6 strain) were purchased and shipped from a vendor (Bar Harbor, ME)
      to the university facility (Urbana, IL) on the day the vaginal plug was found
      (gestation day [GD] 1), arriving at the laboratory on GD 3 after 2 d transport by
      air and ground. Mice (Exp. 1: n = 250, 16.0 +/- 1.2 g BW; Exp. 2: n = 202, 16.2
      +/- 1.2 g BW; Exp. 3: n = 156, 16.4 +/- 1.1 g BW) were housed in individual cages
      and randomly assigned to dietary treatments (Exp. 1: 0 [CON] and 8% SDP in the
      diet, >= 90 mice/diet; Exp. 2: 0, 1, 2, 4, and 8% SDP in the diet, >= 40
      mice/diet; Exp. 3: 0, 1, and 8% SDP in the diet, 48 mice/diet) fed from arrival.
      In Exp. 1 and 2, pregnancy of each mouse was determined on GD 17 based on BW,
      shape of abdomen, and inspection postmortem, and maternal growth performance from
      GD 3 to 17 was measured. On GD 19, pregnant mice in Exp. 2 were euthanized to
      measure number of fetuses and fetal and placental weights. Pregnancy rates in CON
      were low in both Exp. 1 (11%) and Exp. 2 (7%). The SDP consistently and markedly
      increased (P < 0.05) pregnancy rates in both Exp. 1 (49%) and Exp. 2 (35-43%)
      compared with the CON. In Exp. 3, 12 randomly selected mice were euthanized
      immediately after they arrived as an initial group. From GD 4 to 7, randomly
      selected mice were also euthanized each day (12 mice/diet). After euthanasia, the
      abdominal cavity was opened to check pregnancy by uterine inspection and to
      collect blood and uterus samples for immune measurements. The SDP increased (P <
      0.05; 40 vs. 15%) pregnancy rate compared with the CON. Concentrations of
      indicators of inflammation and stress (uterine TNF-alpha and IFN-gamma, and serum
      TNF-alpha, C-reactive protein, and cortisol) were greatest (P < 0.05) and an anti
      inflammatory cytokine (TGF-beta1) was lowest (P < 0.05) soon after arrival, on GD
      3 or 4. The SDP decreased (P < 0.05) the uterine concentrations of TNF-alpha and
      IFN-gamma, and serum TNF-alpha, C-reactive protein, and cortisol, compared with
      the CON, but increased (P < 0.05) the uterine concentration of TGF-beta1. In
      conclusion, dietary SDP improves the low pregnancy rates in this model,
      apparently by attenuating inflammation. 

PMID- 25568379
TI  - Potential of tannin-rich plants for modulating ruminal microbes and ruminal
      fermentation in sheep.
AB  - The objective of this work was to study nutritional strategies for decreasing
      methane production by ruminants fed tropical diets, combining in vitro and in
      vivo methods. The in vitro approach was used to evaluate the dose effect of
      condensed tannins (CT) contained in leaves of Gliricidia sepium, Leucaena
      leucocephala, and Manihot esculenta (39, 75, and 92 g CT/kg DM, respectively) on
      methane production and ruminal fermentation characteristics. Tannin-rich plants
      (TRP) were incubated for 24 h alone or mixed with a natural grassland hay based
      on Dichanthium spp. (control plant), so that proportions of TRP were 0, 0.25,
      0.5, 0.75, and 1.0. Methane production, VFA concentration, and fermented OM
      decreased with increased proportions of TRP. Numerical differences on methane
      production and VFA concentration among TRP sources may be due to differences in
      their CT content, with greater effects for L. leucocephala and M. esculenta than
      for G. sepium. Independently of TRP, the response to increasing doses of CT was
      linear for methane production but quadratic for VFA concentration. As a result,
      at moderate tannin dose, methane decreased more than VFA. The in vivo trial was
      conducted to investigate the effect of TRP on different ruminal microbial
      populations. To this end, 8 rumen-cannulated sheep from 2 breeds (Texel and
      Blackbelly) were used in two 4 * 4 Latin square designs. Diets were fed ad
      libitum and were composed of the same feeds used for the in vitro trial: control
      plant alone or combined with pellets made from TRP leaves at 44% of the diet DM.
      Compared to TRP, concentration of Ruminococcus flavefaciens was greater for the
      control diet and concentration of Ruminococcus albus was least for the control
      diet. The methanogen population was greater for Texel than for Blackbelly. By
      contrast, TRP-containing diets did not affect protozoa or Fibrobacter
      succinogenes numbers. Hence, TRP showed potential for mitigating methane
      production by ruminants. These findings suggest that TRP fed as pellets could be
      used to decrease methane production. 

PMID- 25568380
TI  - Feeding behavior as an early predictor of bovine respiratory disease in North
      American feedlot systems.
AB  - Bovine respiratory disease (BRD), which can cause substantial losses for feedlot
      operations, is often difficult to detect based solely on visual observations. The
      objectives of the current study were to determine a BRD case identification based
      on clinical and laboratory parameters and assess the value of feeding behavior
      for early detection of BRD. Auction-derived, mixed-breed beef steers (n = 213)
      with an average arrival weight of 294 kg were placed at a southern Alberta
      commercial feedlot equipped with an automated feed bunk monitoring system.
      Feeding behavior was recorded continuously (1-s intervals) for 5 wk after arrival
      and summarized into meals. Meals were defined as feeding events that were
      interrupted by less than 300 s nonfeeding. Meal intake (g) and meal time (min)
      were further summarized into daily mean, minimum, maximum, and sum and, together
      with frequency of meals per day, were fit into a discrete survival time analysis
      with a conditional log-log link. Feedlot staff visually evaluated (pen-checked)
      health status twice daily. Within 35 d after arrival, 76% (n = 165) of the steers
      had 1 or more clinical signs of BRD (reluctance to move, crusted nose, nasal or
      ocular discharge, drooped ears or head, and gaunt appearance). Whereas 41 blood
      samples could not be processed due to immediate freezing, for 124 of these
      steers, complete and differential blood cell count, total serum protein, plasma
      fibrinogen, serum concentration of haptoglobin (HP), and serum amyloid A (SAA)
      were determined. The disease definition for BRD was a rectal temperature >= 40.0
      degrees C, at least 2 clinical signs of BRD, and HP > 0.15 mg/mL. It was
      noteworthy that 94% of the 124 steers identified by the feedlot staff with
      clinical signs of BRD had HP > 0.15 mg/mL. An increase in mean meal intake,
      frequency, and mean inter-meal interval was associated with a decreased hazard
      for developing BRD 7 d before visual identification (P < 0.001). Furthermore,
      increased mean mealtime, frequency, and mean inter-meal interval were associated
      with a decreased BRD hazard up to 7 d before feedlot staff noticed clinical
      symptoms (P < 0.001). In conclusion, mean intake per meal as well as mean meal
      time and frequency of meals could be used to predict the hazard of BRD in feedlot
      cattle 7 d before visual detection and could be considered in commercial feedlot
      settings once a predictive algorithm has been developed. 

PMID- 25568381
TI  - Ammonia and greenhouse gas emissions from housed Holstein steers fed different
      levels of diet crude protein.
AB  - The objective of this study was to determine the effect of diet CP levels on
      nitrous oxide (N2O), ammonia (NH3), and methane (CH4) emissions from 1) cattle
      housed in confined settings and 2) cattle manure following surface application to
      incubated soils. Twelve 500-kg Holstein steers were fed diets containing 10% CP
      (10CP) and 13% CP (13CP). The experimental design was a 2 * 2 Latin square
      conducted during two 20-d periods. Diets were fed for 14 d before each
      measurement period to allow for diet acclimation. Steers were housed in
      environmentally controlled rooms allowing for continuous emission measures of
      N2O, NH3, and CH4. At the end of the second period, manure was collected and
      surface applied to incubated soils to verify potential NH3 and N2O emissions. To
      assess emissions from incubated soils, 2 experiments were set up with 3
      replicates each: Exp. 1, in which soil fertilization was based on manure mass
      (496 g of manure), and Exp. 2, in which soil fertilization was based on manure N
      content (targeted at 170 kg N/ha). Manure emissions were monitored for 7 d.
      Steers fed 13CP diets had increased daily NH3 emissions when compared to steers
      fed 10CP diets (32.36 vs. 11.82 +/- 1.10 g NH3/d, respectively; P < 0.01). Daily
      N2O emissions from steers fed 13CP and 10CP diets were significantly different
      only during Period 1 (0.82 vs. 0.31 +/- 0.24 g N2O/d; P = 0.04). Steers fed the
      10CP diet had greater N2O emissions per unit of N consumed than steers fed the
      13CP diet (9.73 vs. 4.26 +/- 1.71 mg N2O/g N intake; P = 0.01). Diet CP levels
      did not affect enteric CH4 production from steers. In terms of soil emissions,
      different CP levels did not affect NH3, N2O, or CH4 emissions when soil
      fertilization was based on manure mass. However, NH3 emissions were reduced when
      manure from steers fed the 10CP diet was applied to soil based on N content.
      Ammonia emissions decreased during the 7-d incubation period. Conversely, N2O
      emissions increased over the period. Our results indicated that management of
      diet CP levels of confined finishing steers mitigates NH3 emissions from steers
      but does not affect enteric CH4. In addition, results suggested that soil
      characteristics might be as important as manure N content to generate NH3 and
      greenhouse gases from soils receiving manure fertilization. 

PMID- 25568382
TI  - Reproductive performance of sows was improved by administration of a sporing
      bacillary probiotic (Bacillus subtilis C-3102).
AB  - This field study assessed the efficacy of a probiotic based on viable spores of
      Bacillus subtilis C-3102 (Calsporin; Calpis Co. Ltd., Japan) on the health status
      and productivity of sows and their litters through 2 full, sequential
      reproductive cycles from service of the first cycle to weaning of the second
      cycle. Fifty-six sows were allocated to 2 experimental groups, an untreated
      control (T1) group and a probiotic-treated (T2) group that received the same
      basal feed as the T1 group plus the probiotic at an approximate allowance of 30
      g/t of feed (3 * 10(5) cfu/g). The offspring of T1 and T2 sows were offered basal
      and T2 creep feed (3 * 10(5) cfu/g), respectively. Health and zootechnical
      parameters of sows and piglets were recorded. Feeding the probiotic to sows and
      piglets resulted in significant benefits, observed in both cycles: 1) improved
      sow body condition during pregnancy (P < 0.05), 2) increased sow feed
      consumption, 3) reduced sow weight loss during lactation (P < 0.05), 4) reduced
      sow weaning-estrus interval (P < 0.05), and 5) higher BW of piglets at weaning (P
      < 0.05). Additionally, a significant (P < 0.05) improvement in piglet birth
      weight and in the number of piglets weaned was observed in the second cycle of T2
      sows, while a significant improvement of mean daily gain of piglets from birth to
      weaning was observed in the first cycle of T2 sows. Microbiological examination
      of fecal samples showed that probiotic treatment significantly reduced both
      Escherichia coli and Clostridium spp. in piglet feces, particularly during the
      second cycle. The data suggested that continuous feed supplementation with the
      probiotic is beneficial for both sows and piglets, since zootechnical benefits
      were observed in both cycles. 

PMID- 25568383
TI  - Inclusion of anti-phospholipase A2 antibody to backgrounding diets on
      performance, feed efficiency, in vitro fermentation, and the acute-phase response
      of growing beef calves.
AB  - In Exp. 1, individual performance and daily DMI was measured on 70 crossbred
      weaned calves during a 70-d period using a GrowSafe system (GrowSafe Systems
      Ltd., Airdrie, AB, Canada) at the University of Florida North Florida Research
      and Education Center Feed Efficiency Facility (FEF). Calves were fed a low
      concentrate (LC) growing diet, blocked by weight and sex, and then randomly
      assigned to pens to receive either no additional supplement (CON; n = 35) or
      receive a supplement of anti-phospholipase A2 antibody (aPLA2) at an inclusion
      rate of 0.6% of the diet DM (n = 35). After the 70-d feed efficiency (FE) trial
      (Phase 1), calves were loaded into a commercial livestock trailer and were driven
      for approximately 1,600 km during 24 h. Upon return to the FEF (Phase 2), calves
      were relocated to the same pens and groups and received the same diets and
      treatments for 28 d. Blood samples from each calf were collected on d 0, 1, 3, 5,
      7, 14, 21, and 28 relative to initiation of transportation and were analyzed for
      determination of concentrations of plasma ceruloplasmin and haptoglobin. In Phase
      1, initial BW (242.0 +/- 3.7 kg; P = 0.92), BW at d 70 (313.0 +/- 4.1 kg; P =
      0.79), and ADG (1.01 +/- 0.02 kg; P = 0.95) were similar between treatments.
      However, daily DMI was greater (P = 0.01) for CON (9.18 +/- 0.15 kg) than aPLA2
      (8.53 +/- 0.15 kg). In addition, residual feed intake was greater (P = 0.002) for
      CON (0.389 +/- 0.110 kg/d) than aPLA2 calves (-0.272 +/- 0.110 kg/d). In Phase 2,
      after transportation, there were no differences between treatments on BW loss due
      to transportation shrink (26.0 +/- 0.6 kg; P = 0.86), BW at d 28 (339.0 +/- 4.1
      kg; P = 0.72), ADG (1.28 +/- 0.03 kg/d; P = 0.72), G:F (0.164 +/- 0.004; P =
      0.83), and concentrations of plasma haptoglobin (0.08 +/- 0.02 mg/mL; P = 0.41).
      However, concentrations of plasma ceruloplasmin were greater (P < 0.001) for CON
      calves (14.3 +/- 0.3 mg/dL) compared to aPLA2 calves (13.0 +/- 0.3 mg/dL). In
      Exp. 2, the effects of aPLA2 inclusion on LC and high-concentrate (HC) substrates
      on in vitro fermentation parameters were assessed. Addition of aPLA2 had no
      effects on in vitro fermentation parameters of LC and HC substrates. In
      conclusion, supplementation of aPLA2 improved FE of growing beef calves when fed
      LC diets in Phase 1 and addition of aPLA2 had no effect on fermentation
      parameters of LC and HC substrates. In addition, calves supplemented with aPLA2
      had reduced concentrations of plasma ceruloplasmin after 24 h of transportation. 

PMID- 25568384
TI  - Serum total iodine concentrations in pasture-fed pregnant ewes and newborn lambs
      challenged by iodine supplementation and goitrogenic kale.
AB  - Iodine deficiency can impair the reproductive performance of livestock and affect
      perinatal mortality of offspring, yet diagnosis of deficiency is complicated and
      guidelines for I supplementation are imprecise. We challenged pasture-grazing
      pregnant ewes with a long-acting I supplement and a goitrogenic forage, then
      monitored their I status during gestation and lactation and in their lambs from
      birth to weaning. Approximately 46 d into gestation, 376 ewes were assigned to 6
      groups comprising 3 supplementation levels * 2 diet regimens. On d 0 the groups
      received an intramuscular injection of iodized oil providing 0, 300, or 400 mg of
      I. They grazed until d 23, then half of each supplementation group were fed
      brassica kale until d 85, then all groups returned to pasture for lambing
      (parturition approximately d 99) and remained there until weaning (d 192). Serum
      total I concentration (STIC) was measured repeatedly in 8 'monitor' ewes per
      group and in their lambs and in milk sampled postpartum. Severity of goiter was
      determined as the thyroid-weight:birth-weight (TW:BW) ratio in 82 newborn dead
      lambs. Mean +/- SE STIC for all ewes was initially 42 +/- 2 (range 24 to 105)
      ug/L. Diet did not affect I concentrations in ewe serum or milk. Responses to
      iodized oil were proportional to dose level; STIC increased to approximately 150
      and 240 ug/L for the 300- and 400-mg I groups and remained greater than 0-mg I
      groups for 161 d (P < 0.05). Milk contained 26, 271, and 425 ug I/L for the 0-,
      300-, and 400-mg I groups, respectively. Mean STIC of lambs from supplemented
      ewes did not differ by diet; concentrations for the 300- and 400-mg I groups were
      237 and 287 ug I/L at birth, and by weaning all groups were similar (62 +/- 3
      ug/L). Lamb STIC measured at birth correlated with exposure to I in utero (R(2) =
      0.59), which was estimated from the area under the curve (AUC) of ewe STIC
      measured during the last 99 d of gestation. Thyroid enlargement in lambs
      affecting the TW:BW ratio was a sensitive indicator of maternal nutrition, being
      greater with kale feeding (1.27 vs. 0.51 g/kg) and lesser with I supplementation
      (0.35 vs. 1.44 g/kg). Results support the use of STIC as a biochemical criterion.
      It was sensitive to the effects of I supplementation with responses in ewes and
      lambs proportional to dose level and it reflected the relationship between ewe
      and lamb I metabolism. However STIC did not discriminate between groups of ewes
      fed pasture vs. goitrogenic forage during pregnancy. 

PMID- 25568386
TI  - Addendum.

PMID- 25568385
TI  - Definition, willingness-to-pay, and ranking of quality attributes of U.S. pork as
      defined by importers in Asia and Mexico.
AB  - A survey was conducted from November 2009 to April 2010 to determine how
      importers of pork define 7 predetermined quality categories (food safety,
      customer service, eating quality, product specification, packaging, visual
      characteristics, and production history) and to estimate willingness-to-pay (WTP)
      and establish best-worst (B/W) scaling (rank) for the 7 quality categories.
      Interviews were conducted in Hong Kong/China (n = 83), Japan (n = 48), Mexico (n
      = 70) and Russia (n = 54) with importers of U.S. pork or those who had purchased
      U.S. pork from distributors in the last 3 yr. Interviews used dynamic routing
      software and were structured such that economic factors for purchase were
      addressed first, allowing all responses to focus on quality. Questions about WTP
      and B/W were asked and then each respondent was asked to define what each quality
      category meant to them. Generalized linear mixed models were used to analyze
      frequency data. Over 70% of interviewees in Hong Kong/China, Japan, and Mexico
      responded that purchase price was influential in deciding whether or not to
      purchase imported pork. This number was lower in Russia, where respondents stated
      tariff rates were also important, indicating market access was a larger issue in
      Russia. Food safety was the most important quality category (price was not
      included as a part of quality) for imported pork followed by specifications.
      Respondents indicated some form of government inspection was how they defined
      food safety, whereas product size, weight, and subcutaneous fat were all included
      in the definition of specifications. Interviewees were more likely to pay
      premiums for customer service and less likely to pay premiums for packaging (P <
      0.05). The premiums that were willing to be paid for guarantees of quality for
      imported pork variety meats were numerically lower than for whole muscle cuts or
      processed products. A guarantee associated with food safety of processed pork
      products was found to be the quality attribute for which importers would be
      willing to pay the highest premium. Production history was found to be the least
      important quality attribute for importers of all types of U.S. pork, except those
      in Japan. Exporters could increase profitability if a guarantee of customer
      service was made. Price, tariffs, and exchange rates are important to pork
      importers; these results indicated that if certain quality attributes could be
      guaranteed, exporters could increase profitability. 

PMID- 25568387
TI  - Updating the assignment of levels of evidence.

PMID- 25568388
TI  - Operative compared with nonoperative treatment of a thoracolumbar burst fracture
      without neurological deficit: a prospective randomized study with follow-up at
      sixteen to twenty-two years.
AB  - BACKGROUND: Studies comparing operative with nonoperative treatment of a stable
      burst fracture of the thoracolumbar junction in neurologically intact patients
      have not shown a meaningful difference at early follow-up. To our knowledge,
      longer-term outcome data have not before been presented. METHODS: From 1992 to
      1998, forty-seven consecutive patients with a stable thoracolumbar burst fracture
      and no neurological deficit were evaluated and randomized to one of two treatment
      groups: operative treatment (posterior or anterior arthrodesis) or nonoperative
      treatment (a body cast or orthosis). We previously reported the results of follow
      up at an average of forty-four months. The current study presents the results of
      long-term follow-up, at an average of eighteen years (range, sixteen to twenty
      two years). As in the earlier study, patients at long-term follow-up indicated
      the degree of pain on a visual analog scale and completed the Roland and Morris
      disability questionnaire, the Oswestry Disability Index (ODI) questionnaire, and
      the Short Form-36 (SF-36) health survey. Work and health status were obtained,
      and patients were evaluated radiographically. RESULTS: Of the original
      operatively treated group of twenty-four patients, follow-up data were obtained
      for nineteen; one patient had died, and four could not be located. Of the
      original nonoperatively treated group of twenty-three patients, data were
      obtained for eighteen; two patients had died, and three could not be located. The
      average kyphosis was not significantly different between the two groups (13
      degrees  for those who received operative treatment compared with 19 degrees  for
      those treated nonoperatively). Median scores for pain (4 cm for the operative
      group and 1.5 cm for the nonoperative group; p = 0.003), ODI scores (20 for the
      operative group and 2 for the nonoperative group; p <0.001) and Roland and Morris
      scores (7 for the operative group and 1 for the nonoperative group; p = 0.001)
      were all significantly better in the group treated nonoperatively. Seven of eight
      SF-36 scores also favored nonoperative treatment. CONCLUSIONS: While early
      analysis (four years) revealed few significant differences between the two
      groups, at long-term follow-up (sixteen to twenty-two years), those with a stable
      burst fracture who were treated nonoperatively reported less pain and better
      function compared with those who were treated surgically.

PMID- 25568390
TI  - Does obesity affect outcomes after hip arthroscopy? A cohort analysis.
AB  - BACKGROUND: Obesity presents a challenging problem in surgical treatment and has
      led to poorer postoperative outcomes. The purpose of this study was to evaluate
      whether hip arthroscopy in the obese patient influences postoperative clinical
      and patient-reported outcome scores. METHODS: From February 2008 to February
      2012, data were collected prospectively on all patients undergoing primary hip
      arthroscopy. A total of 680 patients were included. All patients were assessed
      preoperatively and postoperatively with four patient-reported outcome measures.
      Pain was estimated on the visual analog scale. The patient satisfaction score was
      measured. Three groups were stratified by body mass index. The non-obese group,
      those with a body mass index of <30 kg/m(2) (mean, 23.61 kg/m(2)), included 562
      patients with a mean age of 34.78 years. The class-I obese group, those with a
      body mass index of >=30 to 34.9 kg/m(2) (mean, 33.85 kg/m(2)), included ninety
      four patients with a mean age of 44.02 years. The class-II obese group, those
      with a body mass index of >=35 to 39.9 kg/m(2) (mean, 39.11 kg/m(2)), included
      twenty-four patients with a mean age of 39.33 years. RESULTS: In the non-obese
      group, the score improvement from the preoperative assessment to the two-year
      follow-up visit was 63.41 to 83.81 points for the modified Harris hip score,
      60.86 to 83.62 points for the Non-Arthritic Hip Score, 66.24 to 86.24 points for
      the Hip Outcome Score Activities of Daily Living, and 44.01 to 73.26 points for
      the Hip Outcome Score Sport-Specific Subscale. In the class-I obese group, the
      score improvement from the preoperative assessment to the two-year follow-up
      visit was 54.81 to 75.95 points for the modified Harris hip score, 48.98 to 72.51
      points for the Non-Arthritic Hip Score, 53.22 to 72.99 points for the Hip Outcome
      Score Activities of Daily Living, and 30.56 to 60.75 points for the Hip Outcome
      Score Sport-Specific Subscale. In the class-II obese group, the score improvement
      from the preoperative assessment to the two-year follow-up visit was 50.81 to
      80.01 points for the modified Harris hip score, 42.36 to 72.50 points for the Non
      Arthritic Hip Score, 48.11 to 74.73 points for the Hip Outcome Score Activities
      of Daily Living, and 28.25 to 62.56 points for the Hip Outcome Score Sport
      Specific Subscale. Traction time did not vary significantly between groups (p <
      0.05). CONCLUSIONS: Our study demonstrated that obese patients started with lower
      absolute scores preoperatively and ended with lower overall absolute
      postoperative scores. However, obese patients showed substantial benefit from hip
      arthroscopy and demonstrated a degree of improvement that was similar to that of
      the control non-obese group.

PMID- 25568389
TI  - Evaluation of imaging utilization prior to referral of musculoskeletal tumors: a
      prospective study.
AB  - BACKGROUND: Imaging studies are essential when evaluating a patient with a
      musculoskeletal neoplasm, and they represent a potential waste of resources when
      used inappropriately. The objective of this study was to prospectively evaluate a
      consecutive series of patients for inappropriate utilization of imaging prior to
      referral to a tertiary care facility. Our hypothesis was that advanced imaging is
      overutilized prior to referral of musculoskeletal neoplasms to a tertiary care
      center. METHODS: All new patients referred for evaluation of a musculoskeletal
      neoplasm were prospectively analyzed over a three-month time period. All pre
      referral imaging studies were recorded, including radiographs, computed
      tomographic scans, magnetic resonance imaging scans, bone scans, and 18
      fluorodeoxyglucose positron emission tomography scans. Studies were reviewed by
      two musculoskeletal radiologists and two orthopaedic oncologists and were defined
      with use of specific preselected criteria as inappropriate if they were not
      indicated for diagnosis or treatment, if they required repeating because of
      excessive time since the study was obtained, or if they had poor image quality or
      technique. RESULTS: We evaluated 298 consecutive patients (550 imaging studies).
      The inappropriate utilization rate was 1.5% (three of 204) for radiographs, 36.5%
      (twenty-three of sixty-three) for computed tomographic scans, 26.7% (fifty-six of
      210) for magnetic resonance imaging scans, 45.1% (twenty-three of fifty-one) bone
      scans, and 45.5% (ten of twenty-two) for positron emission tomography scans. The
      overall inappropriate use of advanced imaging (magnetic resonance imaging,
      computed tomography, bone scan, positron emission tomography) was 32.4% (112 of
      346 images). With regard to inappropriate use of magnetic resonance imaging,
      there was no difference between orthopaedic surgeons (28.2%) and primary care
      physicians (26.5%). CONCLUSIONS: Our data indicate a high prevalence (32.4%) of
      inappropriate advanced imaging of musculoskeletal tumors prior to referral. This
      represents a substantial cost to the patient and health-care system, a potential
      delay of referral, an increase in radiation exposure, and identification of other
      incidental findings.

PMID- 25568391
TI  - Intraosseous atypical chondroid tumor or chondrosarcoma grade 1 in patients with
      multiple osteochondromas.
AB  - BACKGROUND: The autosomal dominant condition multiple osteochondromas, formerly
      called multiple hereditary exostoses, is associated with a risk of malignant
      progression of osteochondroma into secondary peripheral chondrosarcoma. Most
      patients with multiple osteochondromas have exostosin-1 or exostosin-2 gene
      mutations. To our knowledge, it has not been previously reported that patients
      may also harbor intraosseous (central) chondroid neoplasms, enchondromas, or
      atypical chondroid tumors or central chondrosarcomas. The combination of
      osteochondroma and enchondromas also exists in patients with metachondromatosis,
      a disorder associated with a protein tyrosine phosphatase non-receptor type 11
      gene mutation. This study aims to establish any correlation between multiple
      osteochondromas and intraosseous cartilaginous neoplasms. METHODS: We
      retrospectively reviewed all histologically proven intraosseous atypical
      chondroid tumors or chondrosarcomas in our prospective nationwide Dutch tertiary
      referral multiple osteochondromas database. Demographic, clinical, radiographic,
      histological, and genetic data were recorded. The institutional medical ethics
      review board approved the study. RESULTS: From 195 adult patients, seven (3.6%)
      were identified with intraosseous atypical chondroid tumor or chondrosarcoma
      World Health Organization grade 1 and had a mean age of forty-two years; five of
      these patients were male. In all cases, radiographic and genetic findings were
      consistent with multiple osteochondromas, not metachondromatosis; three patients
      had an exostosin-1 mutation, four patients had an exostosin-2 mutation, and no
      patients had a protein tyrosine phosphatase, non-receptor type 11 mutation. Six
      patients underwent successful operative treatment without complications or
      recurrences after a mean follow-up duration of forty-eight months (range, twelve
      to 144 months). One patient was scheduled for surgery after biopsy and histologic
      confirmation. Of the seven patients, five (71%) also developed a peripheral
      chondrosarcoma in a known osteochondroma during the study period. CONCLUSIONS:
      Apart from osteochondromas or peripheral chondrosarcomas, multiple
      osteochondromas are also associated with intraosseous chondroid neoplasms,
      potentially resulting in central chondrosarcoma. Therefore, intraosseous lesions
      should not automatically be regarded as innocuous in this patient population.

PMID- 25568392
TI  - Pulmonary function following adult spinal deformity surgery: minimum two-year
      follow-up.
AB  - BACKGROUND: The literature regarding pulmonary function in adult patients with
      spinal deformity is limited, and the effect of spinal deformity surgery on
      pulmonary function has not been clearly understood. We hypothesized that adult
      patients with spinal deformity who had preoperative pulmonary impairment (a
      percent-predicted value of <65% forced expiratory volume in one second [FEV1] as
      measured by pulmonary function test) or who were undergoing revision surgery may
      be at risk for exacerbated decline in pulmonary function. METHODS: Pulmonary
      function test results were prospectively collected for 164 adult patients with
      spinal deformity (mean age, 45.9 years) who underwent surgical treatment at a
      single institution and were followed for a minimum of two years (mean, 2.8
      years). One hundred (61%) of the patients underwent primary surgery, and sixty
      four (39%) of the patients had revision surgery. For the majority of patients
      (77%), a posterior-only surgical approach was used. Radiographs for 154 patients
      were analyzed for major thoracic and sagittal T5-T12 curve magnitude/correction.
      RESULTS: For all patients, we noted a significant change in major thoracic Cobb
      angle, from a mean of 47.4 degrees  to 24.9 degrees (p < 0.001), and in sagittal
      Cobb angle, from a mean of 35.5 degrees  to 30.0 degrees (p < 0.001), as well as
      a significant decline in absolute and percent-predicted pulmonary function
      values, with percent-predicted FEV1 and percent-predicted forced vital capacity
      (FVC) decreasing 5.3% (p < 0.001) and 5.7% (p < 0.001), respectively. A
      clinically significant decline (a decline of >=10% in percent-predicted FEV1) was
      observed in 27% of the patients. The number of patients with pulmonary impairment
      increased nonsignificantly from seventeen (10%) preoperatively to twenty-three
      (14%) after surgery (p = 0.31). Patients with preoperative pulmonary impairment
      demonstrated a significant improvement in absolute and percent-predicted FEV1
      after surgery compared with those without preoperative impairment (2.7% compared
      with -6.2%; p < 0.001). Patients who underwent revision surgery did not differ
      from primary surgery patients in terms of postoperative percent-predicted
      results. However, revision surgery more frequently resulted in a significant
      decline in pulmonary function (twenty-three patients [36%] compared with twenty
      two [22%]; p = 0.05). There was no difference in pulmonary function when
      comparing surgical approaches (anterior/combined anterior-posterior or posterior
      only) or when comparing results by upper-instrumented vertebra (UIV).
      CONCLUSIONS: We found a significant decline in absolute and percent-predicted
      results of pulmonary function tests following surgical correction for spinal
      deformity in adults.

PMID- 25568393
TI  - Navigated pelvic osteotomy and tumor resection: a study assessing the accuracy
      and reproducibility of resection planes in Sawbones and cadavers.
AB  - BACKGROUND: This Sawbones and cadaver study was performed to assess the accuracy
      and reproducibility of pelvic bone cuts made with use of a novel navigation
      system with a navigated osteotome and oscillating saw. METHODS: Using a novel
      navigation system and a three-dimensional planning tool, we navigated pelvic bone
      cuts that were representative of typical cuts made in pelvic tumor resections.
      The system includes a prototype mobile C-arm for intraoperative cone-beam
      computed tomography, real-time optical tracking (Polaris), and three-dimensional
      visualization software. Three-dimensional virtual radiographs were utilized in
      addition to triplanar (axial, sagittal, and coronal) navigation. In part one of
      the study, we navigated twenty-four sacral bone cuts in Sawbones models and
      validated our results in sixteen similar cuts in cadavers. In part two, we
      developed three Sawbones models of pelvic tumors based on actual patient
      scenarios and compared three navigated resections with three non-navigated
      resections for each tumor model. Part three assessed the accuracy of the system
      with multiple users. RESULTS: There were ninety navigated cuts in Sawbones that
      were compared with fifty-four non-navigated cuts. In the navigated Sawbones cuts,
      the mean entry and exit cuts were 1.4 +/- 1 mm and 1.9 +/- 1.2 mm from the
      planned cuts, respectively. In comparison, the entry and exit cuts in Sawbones
      that were not navigated were 2.8 +/- 4.9 mm and 3.5 +/- 4.6 mm away from the
      planned osteotomy site. The navigated cuts were significantly more accurate (p <=
      0.01). In the cadaver study, navigated entry and exit cuts were 1.5 +/- 0.9 mm
      and 2.1 +/- 1.5 mm from the planned cuts. The variation among three different
      users was 1 mm on both the entry and exit cuts. CONCLUSIONS: Navigation to guide
      pelvic bone cuts is accurate and feasible. Three-dimensional radiographs should
      be used for improved accuracy. Navigated cuts were significantly more accurate
      than non-navigated cuts were. A margin of 5 mm between the target tumor volume
      and the planned cut plane would result in a negative margin resection in more
      than 95% of the cuts. CLINICAL RELEVANCE: The accuracy of pelvic bone tumor
      resections and pelvic osteotomies can be improved with navigation to within 5 mm
      of the planned cut.

PMID- 25568394
TI  - Long-term results of tibialis anterior tendon transfer for relapsed idiopathic
      clubfoot treated with the Ponseti method: a follow-up of thirty-seven to fifty
      five years.
AB  - BACKGROUND: Relapse of idiopathic clubfoot deformity after treatment can be
      effectively managed with repeat casting and tibialis anterior tendon transfer
      during early childhood. We evaluated the long-term effects on adult foot function
      after tibialis anterior tendon transfer for relapsed idiopathic clubfoot
      deformity during childhood. METHODS: Thirty-five patients (sixty clubfeet) in
      whom idiopathic clubfoot was treated with the Ponseti method from 1950 to 1967
      were followed. At an average age of forty-seven years (range, thirty-seven to
      fifty-five years), the patients underwent a detailed musculoskeletal examination,
      radiographic evaluation, pedobarographic analysis, and surface electromyography
      (EMG). They also completed three quality-of-life patient questionnaires. RESULTS:
      Fourteen patients (twenty-five clubfeet, 42%) had required repeat casting and
      tibialis anterior tendon transfer in childhood for relapsed clubfoot deformity
      after initial casting and served as the study group. Twenty-one patients (thirty
      five clubfeet, 58%) were successfully treated with initial casting without
      relapse (the reference group). No patient in either group had subsequent relapse
      or required additional operative intervention associated with clubfoot deformity.
      The mean ankle dorsiflexion was similar between the groups. Radiographically, the
      tendon transfer group showed a smaller mean anteroposterior talocalcaneal angle
      and slightly more talar flattening than the reference group with no associated
      clinical differences. Peak pressures, total force distribution, and surface EMG
      results were not significantly different between the groups. Outcome
      questionnaires demonstrated no significant difference between the groups.
      CONCLUSIONS: Tibialis anterior tendon transfer is very effective at preventing
      additional relapse of deformity without affecting long-term foot function of
      patients with idiopathic clubfoot.

PMID- 25568395
TI  - Physician provider type influences utilization and diagnostic utility of magnetic
      resonance imaging of the knee.
AB  - BACKGROUND: Magnetic resonance imaging of the knee is expensive and is neither
      needed nor useful for all patients presenting with knee pain. Our objective was
      to determine the completeness of evaluation prior to ordering magnetic resonance
      imaging of the knee correlated to the ordering providers' postgraduate medical
      training and the rate of positive findings on the subsequent magnetic resonance
      imaging. METHODS: Six hundred consecutive knee magnetic resonance images were
      reviewed, including 200 consecutive knee magnetic resonance imaging examinations
      from each of three provider types: orthopaedic surgeons, non-surgical physicians
      with sports medicine training, and primary care providers. Positive findings on
      magnetic resonance imaging were recorded as well as a history of present illness,
      a physical examination, and radiographs made prior to ordering magnetic resonance
      imaging of the knee. Patient and injury factors were recorded. Differences in
      patient factors, evaluation before magnetic resonance imaging, and positive
      findings were examined. A modified Poisson regression approach was used to
      determine predictors of a proper evaluation before magnetic resonance imaging and
      positive findings on knee magnetic resonance imaging. RESULTS: Orthopaedists and
      non-surgical sports physicians were significantly more likely to document a
      physical examination, to evaluate radiographs made prior to ordering a magnetic
      resonance image, and to identify positive findings on the magnetic resonance
      image (all p < 0.001). In multivariate models, orthopaedists were more likely to
      document a history of present illness (relative risk, 1.05; p = 0.043). Compared
      with primary care physicians, a physical examination was more likely to be
      documented by both non-surgical sports medicine physicians (relative risk, 1.61;
      p < 0.001) and orthopaedists (relative risk, 1.60; p < 0.001) and positive
      magnetic resonance imaging findings were more likely to be found by non-surgical
      sports medicine physicians (relative risk, 1.41; p = 0.012) and by orthopaedists
      (relative risk, 1.44, p = 0.009). Other independent predictors of a magnetic
      resonance imaging study with positive findings were the presence of an acute
      injury by history (relative risk, 2.04; p < 0.001) and younger age (relative
      risk, 0.99; p = 0.021). CONCLUSIONS: Orthopaedists and non-surgical sports
      physicians are more likely to perform and to document a complete evaluation prior
      to ordering a knee magnetic resonance image with a positive finding. More
      musculoskeletal training may be useful to enable primary care physicians to use
      magnetic resonance imaging of the knee in a more efficient manner.

PMID- 25568396
TI  - Synovial fluid interleukin-6 as a predictor of periprosthetic shoulder infection.
AB  - BACKGROUND: Diagnosis of periprosthetic joint infection (PJI) in patients
      undergoing revision shoulder arthroplasty is challenging because of the low
      virulence of the most common infecting organisms. The goal of this study was to
      evaluate the diagnostic utility of measuring synovial fluid interleukin-6 (IL-6)
      levels for identifying PJI of the shoulder. METHODS: Thirty-two consecutive
      patients evaluated for pain at the site of a shoulder arthroplasty were
      prospectively enrolled from November 2012 to September 2013 and underwent
      revision surgery (thirty-five procedures during which samples were obtained for
      synovial fluid IL-6 analysis). Cases were categorized into infection (n = 15) and
      no-infection (n = 20) groups on the basis of objective preoperative and
      intraoperative findings. Twenty patients treated with arthroscopic rotator cuff
      repair were also enrolled to serve as a non-infected control group. Synovial
      fluid was obtained through aspiration intraoperatively for all patients, as well
      as preoperatively for some. Synovial fluid IL-6 levels were measured with use of
      a cytokine immunoassay that utilizes electrochemiluminescent detection. A
      receiver operating characteristic curve was used to determine the diagnostic
      utility of synovial fluid IL-6 analysis. RESULTS: Based on receiver operating
      characteristic curve analysis, synovial fluid IL-6 measurement had an area under
      the curve of 0.891 with an ideal cutoff value of 359.3 pg/mL. The sensitivity,
      specificity, and positive and negative likelihood ratios were 87%, 90%, 8.45, and
      0.15, respectively. Seven patients who underwent a single-stage revision had
      negative results on standard perioperative testing, including the erythrocyte
      sedimentation rate and C-reactive protein levels, but multiple positive
      intraoperative tissue cultures. The level of synovial fluid IL-6 was elevated in
      five of these seven patients, with a median value of 1400 pg/mL. Intraoperative
      synovial fluid IL-6 values correlated well with preoperative IL-6 synovial fluid
      values (correlation = 0.61; p = 0.025) and frozen-section histologic findings (p
      < 0.001). Synovial fluid IL-6 levels were also significantly elevated in patients
      with Propionibacterium acnes infection (p = 0.01). CONCLUSIONS: Measurement of
      synovial fluid IL-6 levels is more sensitive and specific than current
      preoperative testing for predicting positive cultures for patients undergoing
      revision shoulder arthroplasty. This diagnostic accuracy can lead to improved
      decision-making in the management of PJI.

PMID- 25568397
TI  - Gene expression differences between ruptured anterior cruciate ligaments in young
      male and female subjects.
AB  - BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries is two to
      eightfold greater in female compared with male athletes. Anatomic, hormonal, and
      neuromuscular factors have been associated with this disparity. This study
      compared gene expression and structural features in ruptured but otherwise normal
      ACL tissue from young female and male athletes. METHODS: A biopsy sample of
      ruptured ACL tissue (which would normally have been discarded) was obtained
      intraoperatively from seven female and seven male athletes (12.7 to 22.6 years
      old). Each sample was divided into portions for histological and gene expression
      analyses. Specimens for gene analysis were frozen and ground, and RNA was
      extracted and purified. Microarray analysis was performed on RNA isolated from
      four female and three male study participants (13.9 to 18.5 years old) who had a
      noncontact injury. Genes with an expression level that differed significantly
      between these female and male athletes were grouped into functionally associated
      networks with use of IPA software (Qiagen). Three genes of interest were chosen
      for further validation by RT-qPCR (reverse transcription-quantitative polymerase
      chain reaction) analysis of the samples from all fourteen patients. Several
      statistical methods were used to examine sex-related differences. RESULTS:
      Microarray analysis of the RNA isolated from the ruptured ACL tissue from the
      female and male athletes identified thirty-two genes with significant
      differential expression. Fourteen of these genes were not linked to the X or Y
      chromosome. IPA analysis grouped these genes into pathways involving development
      and function of skeletal muscle and growth, maintenance, and proliferation of
      cells. RT-qPCR confirmed significant differences in expression of three selected
      genes: ACAN (aggrecan) and FMOD (fibromodulin) were upregulated in female
      compared with male study participants, and WISP2 (WNT1 inducible signaling
      pathway protein 2) was downregulated. No morphological differences among the
      ruptured tissue from the various participants were apparent on histological
      examination. CONCLUSIONS: The genes identified in this study as differing
      distinctly according to sex produce major molecules in the ACL extracellular
      matrix. Significant upregulation of ACAN and FMOD (which regulate the matrix) and
      downregulation of WISP2 (which is involved in collagen turnover and production)
      may account for the weaker ACLs in female compared with male individuals.

PMID- 25568398
TI  - Measuring patient satisfaction in orthopaedic surgery.
AB  - In addition to their wish to understand the clinical results of orthopaedic
      interventions, clinicians, patients, and payers are increasingly interested in
      patient satisfaction, both with the process of care and with outcomes. The
      construct of satisfaction is complex and depends on the context in which care
      takes place, including the nature of treatment, its setting, and most importantly
      the expectation of patients prior to treatment. The characteristics of scales
      that are effective measures of satisfaction are the same as those of all
      effective measurement instruments--i.e., reliability, validity, and
      responsiveness. Measurement of patient satisfaction may be especially important
      in evaluations of established procedures and processes so that the value of those
      procedures and processes to patients can be more completely understood.

PMID- 25568399
TI  - International elective during orthopaedic residency in North America: perceived
      barriers and opportunities.

PMID- 25568400
TI  - How do you know it is true? Integrity in research and publications: AOA critical
      issues.
AB  - High-quality medical care is the result of clinical decisions based upon
      scientific principles garnered from basic, translational, and clinical research.
      Information regarding the natural history of diseases and their responses to
      various treatments is introduced into the medical literature through the
      approximately one million PubMed journal articles published each year.
      Pharmaceutical and device companies, universities, departments, and researchers
      all stand to gain from research publication. Basic and translational research is
      highly competitive. Success in obtaining research funding and career advancement
      requires scientific publication in the medical literature. Clinical research
      findings can lead to changes in the pattern of orthopaedic practice and have
      implications for the utilization of pharmaceuticals and orthopaedic devices.
      Research findings can be biased by ownership of patents and materials, funding
      sources, and consulting arrangements. The current high-stakes research
      environment has been characterized by an increase in plagiarism, falsification or
      manipulation of data, selected presentation of results, research bias, and
      inappropriate statistical analyses. It is the responsibility of the orthopaedic
      community to work collaboratively with industry, universities, departments, and
      medical researchers and educators to ensure the integrity of the content of the
      orthopaedic literature and to enable the incorporation of best practices in the
      care of orthopaedic patients. 

PMID- 25568401
TI  - The fellowship match process: the history and a report of the current experience.

PMID- 25568402
TI  - Long-term results still favor nonoperative treatment of stable thoracolumbar
      burst fractures: commentary on an article by Kirkham B. Wood, MD, et al.:
      "Operative compared with nonoperative treatment of a thoracolumbar burst fracture
      without neurological deficit. A prospective randomized study with follow-up at
      sixteen to twenty-two years".

PMID- 25568403
TI  - Central chondrosarcoma in patients with multiple osteochondromas: commentary on
      an article by Annemarie L. Goud, MD, PhD, et al: "Intraosseous atypical chondroid
      tumor or chondrosarcoma grade 1 in patients with multiple osteochondromas".

PMID- 25568405
TI  - From needle to knife.
AB  - Trauma and Orthopaedic care has been through a rapid evolution over the past few
      decades. This Editorial discusses some of the advances.

PMID- 25568404
TI  - After the bone and joint decade: it is still time to educate on the
      musculoskeletal system: commentary on an article by James D. Wylie, MD, MHS, et
      al.: "Physician provider type influences utilization and diagnostic utility of
      magnetic resonance imaging of the knee".

PMID- 25568406
TI  - The assessment of outcome after total knee arthroplasty: are we there yet?
AB  - The routine use of patient reported outcome measures (PROMs) in evaluating the
      outcome after arthroplasty by healthcare organisations reflects a growing
      recognition of the importance of patients' perspectives in improving treatment.
      Although widely embraced in the NHS, there are concerns that PROMs are being used
      beyond their means due to a poor understanding of their limitations. This paper
      reviews some of the current challenges in using PROMs to evaluate total knee
      arthroplasty. It highlights alternative methods that have been used to improve
      the assessment of outcome.

PMID- 25568408
TI  - Which patient characteristics influence length of hospital stay after primary
      total hip arthroplasty in a 'fast-track' setting?
AB  - After implementation of a 'fast-track' rehabilitation protocol in our hospital,
      mean length of hospital stay for primary total hip arthroplasty decreased from
      4.6 to 2.9 nights for unselected patients. However, despite this reduction there
      was still a wide range across the patients' hospital duration. The purpose of
      this study was to identify which specific patient characteristics influence
      length of stay after successful implementation of a 'fast-track' rehabilitation
      protocol. A total of 477 patients (317 female and 160 male, mean age 71.0 years;
      39.3 to 92.6, mean BMI 27.0 kg/m(2);18.8 to 45.2) who underwent primary total hip
      arthroplasty between 1 February 2011 and 31 January 2013, were included in this
      retrospective cohort study. A length of stay greater than the median was
      considered as an increased duration. Logistic regression analyses were performed
      to identify potential factors associated with increased durations. Median length
      of stay was two nights (interquartile range 1), and the mean length of stay 2.9
      nights (1 to 75). In all, 266 patients had a length of stay <= two nights. Age
      (odds ratio (OR) 2.46; 95% confidence intervals (CI) 1.72 to 3.51; p < 0.001),
      living situation (alone vs living together with cohabitants, OR 2.09; 95% CI 1.33
      to 3.30; p = 0.002) and approach (anterior approach vs lateral, OR 0.29; 95% CI
      0.19 to 0.46; p < 0.001) (posterolateral approach vs lateral, OR 0.24; 95% CI
      0.10 to 0.55; p < 0.001) were factors that were significantly associated with
      increased length of stay in the multivariable logistic regression model.

PMID- 25568407
TI  - Validation of primary metal-on-metal hip arthroplasties on the National Joint
      Registry for England, Wales and Northern Ireland using data from the London
      Implant Retrieval Centre: a study using the NJR dataset.
AB  - Arthroplasty registries are important for the surveillance of joint replacements
      and the evaluation of outcome. Independent validation of registry data ensures
      high quality. The ability for orthopaedic implant retrieval centres to validate
      registry data is not known. We analysed data from the National Joint Registry for
      England, Wales and Northern Ireland (NJR) for primary metal-on-metal hip
      arthroplasties performed between 2003 and 2013. Records were linked to the London
      Implant Retrieval Centre (RC) for validation. A total of 67,045 procedures on the
      NJR and 782 revised pairs of components from the RC were included. We were able
      to link 476 procedures (60.9%) recorded with the RC to the NJR successfully.
      However, 306 procedures (39.1%) could not be linked. The outcome recorded by the
      NJR (as either revised, unrevised or death) for a primary procedure was incorrect
      in 79 linked cases (16.6%). The rate of registry-retrieval linkage and correct
      assignment of outcome code improved over time. The rates of error for component
      reference numbers on the NJR were as follows: femoral head category number 14/229
      (5.0%); femoral head batch number 13/232 (5.3%); acetabular component category
      number 2/293 (0.7%) and acetabular component batch number 24/347 (6.5%). Registry
      retrieval linkage provided a novel means for the validation of data, particularly
      for component fields. This study suggests that NJR reports may underestimate
      rates of revision for many types of metal-on-metal hip replacement. This is
      topical given the increasing scope for NJR data. We recommend a system for
      continuous independent evaluation of the quality and validity of NJR data.

PMID- 25568409
TI  - The incidence of stress fracture following peri-acetabular osteotomy: an under
      reported complication.
AB  - Stress fractures occurring in the pubis and ischium after peri-acetabular
      osteotomy (PAO) are not well recognised, with a reported incidence of 2% to 3%.
      The purpose of this study was to analyse the incidence of stress fracture after
      Bernese PAO under the care of two high-volume surgeons. The study included 359
      patients (48 men, 311 women) operated on at a mean age of 31.1 years (15 to 56),
      with a mean follow-up of 26 months (6 to 64). Complete follow-up radiographs were
      available for 348 patients, 64 of whom (18.4%) developed a stress fracture of the
      inferior pubic ramus, which was noted at a mean of 9.1 weeks (5 to 55) after
      surgery. Most (58; 91%) healed. In 40 of the patients with a stress fracture
      (62.5%), pubic nonunion also occurred. Those with a stress fracture were
      significantly older (mean 33.9 years (16 to 50) vs 30.5 years (15 to 56), p =
      0.002) and had significantly more mean pre-operative deformity: mean centre-edge
      angle (9.8 degrees  (-9.5 to 35) vs 12.4 degrees  (-33 to 28), p = 0.04) and mean
      Tonnis angle (22.8 degrees  (0 to 45) vs 18.7 degrees  (-2 to 38), p < 0.001).
      The pubic nonunion rate was significantly higher in those with a stress fracture
      (62.5% vs 7%, p < 0.001), with regression analysis revealing that these patients
      had 11.8 times higher risk than those without nonunion.

PMID- 25568410
TI  - Obesity is a major risk factor for the development of complications after peri
      acetabular osteotomy.
AB  - Obesity is a risk factor for complications following many orthopaedic procedures.
      The purpose of this study was to investigate whether obesity was an independent
      risk factor increasing the rate of complications following periacetabular
      osteotomy (PAO) and to determine whether radiographic correction after PAO was
      affected by obesity. We retrospectively collected demographic, clinical and
      radiographic data on 280 patients (231 women; 82.5% and 49 men; 17.5%) who were
      followed for a mean of 48 months (12 to 60) after PAO. A total of 65 patients
      (23.2%) were obese (body mass index (BMI) > 30 kg/m(2)). Univariate and
      multivariate analysis demonstrated that BMI was an independent risk factor
      associated with the severity of the complications. The average probability of a
      patient developing a major complication was 22% (95% confidence interval (CI)
      11.78 to 38.21) for an obese patient compared with 3% (95% CI 1.39 to 6.58) for a
      non-obese patient The odds of a patient developing a major complication were 11
      times higher (95% CI 4.71 to 17.60, p < 0.0001) for an obese compared with a non
      obese patient. Following PAO surgery, there was no difference in radiographic
      correction between obese and non-obese patients. PAO procedures in obese patients
      correct the deformity effectively but are associated with an increased rate of
      complications.

PMID- 25568411
TI  - Positive effect of removal of subchondral bone plate for cemented acetabular
      component fixation in total hip arthroplasty: a randomised RSA study with ten
      year follow-up.
AB  - We hypothesised that the removal of the subchondral bone plate (SCBP) for
      cemented acetabular component fixation in total hip arthroplasty (THA) offers
      advantages over retention by improving the cement-bone interface, without
      jeopardising implant stability. We have previously published two-year follow-up
      data of a randomised controlled trial (RCT), in which 50 patients with primary
      osteoarthritis were randomised to either retention or removal of the SCBP. The
      mean age of the retention group (n = 25, 13 males) was 70.0 years (sd 6.8). The
      mean age in the removal group (n = 25, 16 males) was 70.3 years (sd 7.9). Now we
      have followed up the patients at six (retention group, n = 21; removal group, n =
      20) and ten years (retention group: n = 17, removal group: n = 18), administering
      clinical outcome questionnaires and radiostereometric analysis (RSA), and
      determining the presence of radiolucent lines (RLLs) on conventional radiographs.
      RSA demonstrated similar translation and rotation patterns up to six years.
      Between six and ten years, proximal acetabular component migration and changes of
      inclination were larger in the retention group, although the mean differences did
      not reach statistical significance. Differences in migration were driven by two
      patients in the SCBP retention group with extensive migration versus none in the
      SCBP removal group. The significant difference (p < 0.001) in the development of
      radiolucent lines in the retention group, previously observed at two years,
      increased even further during the course of follow-up (p < 0.001). While
      recognising SCBP removal is a more demanding technique, we conclude that,
      wherever possible, the SCBP should be removed to improve the cement-bone
      interface in order to maximise acetabular component stability and longevity.

PMID- 25568412
TI  - Is tantalum protective against infection in revision total hip arthroplasty?
AB  - We hypothesised that the use of tantalum (Ta) acetabular components in revision
      total hip arthroplasty (THA) was protective against subsequent failure due to
      infection. We identified 966 patients (421 men, 545 women and 990 hips) who had
      undergone revision THA between 2000 and 2013. The mean follow up was 40.2 months
      (3 months to 13.1 years). The mean age of the men and women was 62.3 years (31 to
      90) and 65.1 years (25 to 92), respectively. Titanium (Ti) acetabular components
      were used in 536 hips while Ta components were used in 454 hips. In total, 73
      (7.3%) hips experienced subsequent acetabular failure. The incidence of failure
      was lower in the Ta group at 4.4% (20/454) compared with 9.9% (53/536) in the Ti
      group (p < 0.001, odds ratio 2.38; 95% CI 1.37 to 4.27). Among the 144 hips (64
      Ta, 80 Ti) for which revision had been performed because of infection, failure
      due to a subsequent infection was lower in the Ta group at 3.1% (2/64) compared
      with 17.5% (14/80) for the Ti group (p = 0.006). Thus, the use of Ta acetabular
      components during revision THA was associated with a lower incidence of failure
      from all causes and Ta components were associated with a lower incidence of
      subsequent infection when used in patients with periprosthetic joint infection.

PMID- 25568413
TI  - Congruence and joint space width alterations of the medial compartment following
      lateral unicompartmental knee arthroplasty.
AB  - Progressive degenerative changes in the medial compartment of the knee following
      lateral unicompartmental arthroplasty (UKA) remains a leading indication for
      revision surgery. The purpose of this study is to evaluate changes in the
      congruence and joint space width (JSW) of the medial compartment following
      lateral UKA. The congruence of the medial compartment of 53 knees (24 men, 23
      women, mean age 13.1 years; sd 62.1) following lateral UKA was evaluated pre
      operatively and six weeks post-operatively, and compared with 41 normal knees (26
      men, 15 women, mean age 33.7 years; sd 6.4), using an Interactive closest point
      algorithm which calculated the congruence index (CI) by performing a rigid
      transformation that best aligns the digitised tibial and femoral surfaces. Inner,
      middle and outer JSWs were measured by sub-dividing the medial compartment into
      four quarters on pre- and post-operative, weight bearing tunnel view radiographs.
      The mean CI of knees following lateral UKA significantly improved from 0.92 (sd
      0.06) pre-operatively to 0.96 (sd 0.02) (p < 0.001) six weeks post-operatively.
      The mean CI of the healthy control group was 0.99 sd 0.01. Post-operatively, the
      mean inner JSW increased (p = 0.006) and the outer decreased (p = 0.002). The JSW
      was restored post-operatively as no significant differences were noted in all
      three locations compared with the control group (inner JSW p = 0.43; middle JSW p
      = 0.019, outer JSW p = 0.51). Our data suggest that a well conducted lateral UKA
      may improve the congruence and normalise the JSW of the medial compartment,
      potentially preventing progression of degenerative change.

PMID- 25568414
TI  - A comparison of patient-specific and conventional instrumentation for total knee
      arthroplasty: a multicentre randomised controlled trial.
AB  - In this study we randomised 140 patients who were due to undergo primary total
      knee arthroplasty (TKA) to have the procedure performed using either patient
      specific cutting guides (PSCG) or conventional instrumentation (CI). The primary
      outcome measure was the mechanical axis, as measured at three months on a
      standing long-leg radiograph by the hip-knee-ankle (HKA) angle. This was
      undertaken by an independent observer who was blinded to the instrumentation.
      Secondary outcome measures were component positioning, operating time, Knee
      Society and Oxford knee scores, blood loss and length of hospital stay. A total
      of 126 patients (67 in the CI group and 59 in the PSCG group) had complete
      clinical and radiological data. There were 88 females and 52 males with a mean
      age of 69.3 years (47 to 84) and a mean BMI of 28.6 kg/m(2) (20.2 to 40.8). The
      mean HKA angle was 178.9 degrees  (172.5 to 183.4) in the CI group and 178.2
      degrees  (172.4 to 183.4) in the PSCG group (p = 0.34). Outliers were identified
      in 22 of 67 knees (32.8%) in the CI group and 19 of 59 knees (32.2%) in the PSCG
      group (p = 0.99). There was no significant difference in the clinical results (p
      = 0.95 and 0.59, respectively). Operating time, blood loss and length of hospital
      stay were not significantly reduced (p = 0.09, 0.58 and 0.50, respectively) when
      using PSCG. The use of PSCG in primary TKA did not reduce the proportion of
      outliers as measured by post-operative coronal alignment.

PMID- 25568415
TI  - Implant design influences patient outcome after total knee arthroplasty: a
      prospective double-blind randomised controlled trial.
AB  - Total knee arthroplasty (TKA) is an established and successful procedure.
      However, the design of prostheses continues to be modified in an attempt to
      optimise the functional outcome of the patient. The aim of this study was to
      determine if patient outcome after TKA was influenced by the design of the
      prosthesis used. A total of 212 patients (mean age 69; 43 to 92; 131 female
      (62%), 81 male (32%)) were enrolled in a single centre double-blind trial and
      randomised to receive either a Kinemax (group 1) or a Triathlon (group 2) TKA.
      Patients were assessed pre-operatively, at six weeks, six months, one year and
      three years after surgery. The outcome assessments used were the Oxford Knee
      Score; range of movement; pain numerical rating scales; lower limb power output;
      timed functional assessment battery and a satisfaction survey. Data were assessed
      incorporating change over all assessment time points, using repeated measures
      analysis of variance longitudinal mixed models. Implant group 2 showed a
      significantly greater range of movement (p = 0.009), greater lower limb power
      output (p = 0.026) and reduced report of 'worst daily pain' (p = 0.003) over the
      three years of follow-up. Differences in Oxford Knee Score (p = 0.09), report of
      'average daily pain' (p = 0.57) and timed functional performance tasks (p = 0.23)
      did not reach statistical significance. Satisfaction with outcome was
      significantly better in group 2 (p = 0.001). These results suggest that patient
      outcome after TKA can be influenced by the prosthesis used.

PMID- 25568416
TI  - Interleukin-6 in two-stage revision arthroplasty: what is the threshold value to
      exclude persistent infection before re-implanatation?
AB  - The purpose of this study was to evaluate whether the serum level of interleukin
      6 (IL-6) could be used to identify the persistence of infection after the first
      stage of a two-stage revision for periprosthetic joint infection. Between 2010
      and 2011, we prospectively studied 55 patients (23 men, 32 women; mean age 69.5
      years; 36 to 86) with a periprosthetic joint infection. Bacteria were identified
      in two intra-operative tissue samples during re-implantation in 16 patients.
      These cases were classified as representing persistent infection. To calculate a
      precise cut-off value which could be used in everyday clinical practice, a 3 x 2
      contingency table was constructed and manually defined. We found that a serum IL
      6 >= 13 pg/mL can be regarded as indicating infection: its positive-predictive
      value is 90.9%. A serum IL-6 <= 8 pg/mL can be regarded as indicating an absence
      of infection: its negative predictive value is 92.1%. The serum IL-6 level seems
      to be a reasonable marker for identifying persistent infection after the first
      stage of a revision joint arthroplasty and before attempting re-implantation.

PMID- 25568417
TI  - Outcome of one-stage correction of deformities of the ankle and hindfoot and
      fusion in Charcot neuroarthropathy using a retrograde intramedullary hindfoot
      arthrodesis nail.
AB  - We report the outcomes of 20 patients (12 men, 8 women, 21 feet) with Charcot
      neuro-arthropathy who underwent correction of deformities of the ankle and
      hindfoot using retrograde intramedullary nail arthrodesis. The mean age of the
      patients was 62.6 years (46 to 83); their mean BMI was 32.7 (15 to 47) and their
      median American Society of Anaesthetists score was 3 (2 to 4). All presented with
      severe deformities and 15 had chronic ulceration. All were treated with
      reconstructive surgery and seven underwent simultaneous midfoot fusion using a
      bolt, locking plate or a combination of both. At a mean follow-up of 26 months (8
      to 54), limb salvage was achieved in all patients and 12 patients (80%) with
      ulceration achieved healing and all but one patient regained independent
      mobilisation. There was failure of fixation with a broken nail requiring revision
      surgery in one patient. Migration of distal locking screws occurred only when
      standard screws had been used but not with hydroxyapatite-coated screws. The mean
      American Academy of Orthopaedic Surgeons Foot and Ankle (AAOS-FAO) score improved
      from 50.7 (17 to 88) to 65.2 (22 to 88), (p = 0.015). The mean Short Form (SF)-36
      Health Survey Physical Component Score improved from 25.2 (16.4 to 42.8) to 29.8
      (17.7 to 44.2), (p = 0.003) and the mean Euroqol EQ-5D-5L score improved from
      0.63 (0.51 to 0.78) to 0.67 (0.57 to 0.84), (p = 0.012). Single-stage correction
      of deformity using an intramedullary hindfoot arthrodesis nail is a good form of
      treatment for patients with severe Charcot hindfoot deformity, ulceration and
      instability provided a multidisciplinary care plan is delivered.

PMID- 25568418
TI  - The biological response to a failed extra-articular polyester ligament used for
      AC Joint reconstruction at the shoulder girdle: a retrieval analysis of five
      cases.
AB  - The LockDown device (previously called Surgilig) is a braided polyester mesh
      which is mostly used to reconstruct the dislocated acromioclavicular joint. More
      than 11,000 have been implanted worldwide. Little is known about the tissue
      reaction to the device nor to its wear products when implanted in an extra
      articular site in humans. This is of importance as an adverse immunological
      reaction could result in osteolysis or damage to the local tissues, thereby
      affecting the longevity of the implant. We analysed the histology of five
      LockDown implants retrieved from five patients over the last seven years by one
      of the senior authors. Routine analysis was carried out in all five cases and
      immunohistochemistry in one. The LockDown device acts as a scaffold for
      connective tissue which forms an investing fibrous pseudoligament. The
      immunological response at the histological level seems favourable with a limited
      histiocytic and giant cell response to micron-sized wear particles. The
      connective tissue envelope around the implant is less organised than a native
      ligament.

PMID- 25568419
TI  - The prevalence of vitamin D deficiency in patients with vertebral fragility
      fractures.
AB  - Hypovitaminosis D has been identified as a common risk factor for fragility
      fractures and poor fracture healing. Epidemiological data on vitamin D deficiency
      have been gathered in various populations, but the association between vertebral
      fragility fractures and hypovitaminosis D, especially in males, remains unclear.
      The purpose of this study was to evaluate serum levels of 25-hydroxyvitamin D (25
      OH D) in patients presenting with vertebral fragility fractures and to determine
      whether patients with a vertebral fracture were at greater risk of
      hypovitaminosis D than a control population. Furthermore, we studied the seasonal
      variations in the serum vitamin D levels of tested patients in order to clarify
      the relationship between other known risk factors for osteoporosis and vitamin D
      levels. We measured the serum 25-OH D levels of 246 patients admitted with
      vertebral fractures (105 men, 141 female, mean age 69 years, sd 8.5), and in 392
      orthopaedic patients with back pain and no fractures (219 men, 173 female, mean
      age 63 years, sd 11) to evaluate the prevalence of vitamin D insufficiency.
      Statistical analysis found a significant difference in vitamin D levels between
      patients with vertebral fragility fracture and the control group (p = 0.036). In
      addition, there was a significant main effect of the tested variables: obesity (p
      < 0.001), nicotine abuse (p = 0.002) and diabetes mellitus (p < 0.001). No
      statistical difference was found between vitamin D levels and gender (p = 0.34).
      Vitamin D insufficiency was shown to be a risk factor for vertebral fragility
      fractures in both men and women.

PMID- 25568420
TI  - Hemiarthroplasty using cemented or uncemented stems of proven design: a
      comparative study.
AB  - National Institute of Clinical Excellence guidelines state that cemented stems
      with an Orthopaedic Data Evaluation Panel (ODEP) rating of > 3B should be used
      for hemiarthroplasty when treating an intracapsular fracture of the femoral neck.
      These recommendations are based on studies in which most, if not all stems, did
      not hold such a rating. This case-control study compared the outcome of
      hemiarthroplasty using a cemented (Exeter) or uncemented (Corail) femoral stem.
      These are the two prostheses most commonly used in hip arthroplasty in the UK.
      Data were obtained from two centres; most patients had undergone hemiarthroplasty
      using a cemented Exeter stem (n = 292/412). Patients were matched for all factors
      that have been shown to influence mortality after an intracapsular fracture of
      the neck of the femur. Outcome measures included: complications, re-operations
      and mortality rates at two, seven, 30 and 365 days post-operatively. Comparable
      outcomes for the two stems were seen. There were more intra-operative
      complications in the uncemented group (13% vs 0%), but the cemented group had a
      greater mortality in the early post-operative period (n = 6). There was no
      overall difference in the rate of re-operation (5%) or death (365 days: 26%)
      between the two groups at any time post-operatively. This study therefore
      supports the use of both cemented and uncemented stems of proven design, with an
      ODEP rating of 10A, in patients with an intracapsular fracture of the neck of the
      femur.

PMID- 25568421
TI  - Independent validation of the Nottingham Hip Fracture Score and identification of
      regional variation in patient risk within England.
AB  - The Nottingham Hip Fracture Score (NHFS) was developed to assess the risk of
      death following a fracture of the hip, based on pre-operative patient
      characteristics. We performed an independent validation of the NHFS, assessed the
      degree of geographical variation that exists between different units within the
      United Kingdom and attempted to define a NHFS level that is associated with high
      risk of mortality. The NHFS was calculated retrospectively for consecutive
      patients presenting with a fracture of the hip to two hospitals in England. The
      observed 30-day mortality for each NHFS cohort was compared with that predicted
      by the NHFS using the Hosmer-Lemeshow test. The distribution of NHFS in the
      observed group was compared with data from other hospitals in the United Kingdom.
      The proportion of patients identified as high risk and the mortality within the
      high risk group were assessed for groups defined using different thresholds for
      the NHFS. In all 1079 hip fractures were included in the analysis, with a mean
      age of 83 years (60 to 105), 284 (26%) male. Overall 30-day mortality was 7.3%.
      The NHFS was a significant predictor of 30-day mortality. Statistically
      significant differences in the distribution of the NHFS were present between
      different units in England (p < 0.001). A NHFS >= 6 appears to be an appropriate
      cut-point to identify patients at high risk of mortality following a fracture of
      the hip.

PMID- 25568422
TI  - Early surgery for patients with a fracture of the hip decreases 30-day mortality.
AB  - There has been extensive discussion about the effect of delay to surgery on
      mortality in patients sustaining a fracture of the hip. Despite the low level of
      evidence provided by many studies, a consensus has been accepted that delay of >
      48 hours is detrimental to survival. The aim of this prospective observational
      study was to determine if early surgery confers a survival benefit at 30 days.
      Between 1989 and 2013, data were prospectively collected on patients sustaining a
      fracture of the hip at Peterborough City Hospital. They were divided into groups
      according to the time interval between admission and surgery. These thresholds
      ranged from < 6 hours to between 49 and 72 hours. The outcome which was assessed
      was the 30-day mortality. Adjustment for confounders was performed using
      multivariate binary logistic regression analysis. In all, 6638 patients aged > 60
      years were included. Worsening American Society of Anaesthesiologists grade (p <
      0.001), increased age (p < 0.001) and extracapsular fracture (p < 0.019)
      increased the risk of 30-day mortality. Increasing mobility score (p = 0.014),
      mini mental test score (p < 0.001) and female gender (p = 0.014) improved
      survival. After adjusting for these confounders, surgery before 12 hours improved
      survival compared with surgery after 12 hours (p = 0.013). Beyond this the
      increasing delay to surgery did not significantly affect the 30-day mortality.

PMID- 25568423
TI  - Arthrofibrosis of the knee following a fracture of the tibial plateau.
AB  - The aim of this study was to report the incidence of arthrofibrosis of the knee
      and identify risk factors for its development following a fracture of the tibial
      plateau. We carried out a retrospective review of 186 patients (114 male, 72
      female) with a fracture of the tibial plateau who underwent open reduction and
      internal fixation. Their mean age was 46.4 years (19 to 83) and the mean follow
      up was16.0 months (6 to 80). A total of 27 patients (14.5%) developed
      arthrofibrosis requiring a further intervention. Using multivariate regression
      analysis, the use of a provisional external fixator (odds ratio (OR) 4.63, 95%
      confidence interval (CI) 1.26 to 17.7, p = 0.021) was significantly associated
      with the development of arthrofibrosis. Similarly, the use of a continuous
      passive movement (CPM) machine was associated with significantly less development
      of arthrofibrosis (OR = 0.32, 95% CI 0.11 to 0.83, p = 0.024). The effect of time
      in an external fixator was found to be significant, with each extra day of
      external fixation increasing the odds of requiring manipulation under anaesthesia
      (MUA) or quadricepsplasty by 10% (OR = 1.10, p = 0.030). High-energy fracture,
      surgical approach, infection and use of tobacco were not associated with the
      development of arthrofibrosis. Patients with a successful MUA had significantly
      less time to MUA (mean 2.9 months; sd 1.25) than those with an unsuccessful MUA
      (mean 4.86 months; sd 2.61, p = 0.014). For those with limited movement,
      therefore, performing an MUA within three months of the injury may result in a
      better range of movement. Based our results, CPM following operative fixation for
      a fracture of the tibial plateau may reduce the risk of the development of
      arthrofibrosis, particularly in patients who also undergo prolonged provisional
      external fixation.

PMID- 25568424
TI  - Does amputation offer any survival benefit over limb salvage in osteosarcoma
      patients with poor chemonecrosis and close margins?
AB  - A poor response to chemotherapy (<= 90% necrosis) for osteosarcomas leads to
      poorer survival and an increased risk of local recurrence, particularly if there
      is a close margin of excision. We evaluated whether amputation confers any
      survival benefit over limb salvage surgery (LSS) with narrow margins in patients
      who respond poorly to chemotherapy. We only analysed patients with an
      osteosarcoma of the limb, a poor response to chemotherapy and close margins on
      LSS (marginal/intralesional) or primary amputation: 360 patients (36 LSS
      (intralesional margins), 197 LSS (marginal margins) and 127 amputations) were
      included. Local recurrence developed in 13 (36%) following LSS with intralesional
      margins, and 39 (20%) following LSS with marginal margins. There was no local
      recurrence in patients who underwent amputation. The five-year survival for all
      patients was 41% (95% confidence interval (CI) 35 to 46), but for those treated
      by LSS with marginal margins was 46.2% (95% CI 38 to 53), 36.3% (95% CI 27 to 45)
      for those treated by amputation, and 28% (95 CI 14 to 44) for those treated by
      LSS with intralesional margins. Patients who had LSS and then developed local
      recurrence as a first event had the same survival as those who had primary
      amputation without local recurrence. Prophylactic adjuvant radiotherapy was used
      in 40 patients but had no discernible effect in preventing local recurrence.
      Although amputation offered better local control, it conferred no clear survival
      benefit over LSS with marginal margins in these patients with a poor overall
      prognosis.

PMID- 25568425
TI  - The MRI appearances of cancellous allograft bone chips after the excision of bone
      tumours.
AB  - Cancellous allograft bone chips are commonly used in the reconstruction of
      defects in bone after removal of benign tumours. We investigated the MRI features
      of grafted bone chips and their change over time, and compared them with those
      with recurrent tumour. We retrospectively reviewed 66 post-operative MRIs from 34
      patients who had undergone curettage and grafting with cancellous bone chips to
      fill the defect after excision of a tumour. All grafts showed consistent features
      at least six months after grafting: homogeneous intermediate or low signal
      intensities with or without scattered hyperintense foci (speckled
      hyperintensities) on T1 images; high signal intensities with scattered
      hypointense foci (speckled hypointensities) on T2 images, and peripheral rim
      enhancement with or without central heterogeneous enhancements on enhanced
      images. Incorporation of the graft occurred from the periphery to the centre, and
      was completed within three years. Recurrent lesions consistently showed the same
      signal intensities as those of pre-operative MRIs of the primary lesions. There
      were four misdiagnoses, three of which were chondroid tumours. We identified
      typical MRI features and clarified the incorporation process of grafted
      cancellous allograft bone chips. The most important characteristics of recurrent
      tumours were that they showed the same signal intensities as the primary tumours.
      It might sometimes be difficult to differentiate grafted cancellous allograft
      bone chips from a recurrent chondroid tumour.

PMID- 25568426
TI  - The results of an extensive soft-tissue procedure in the treatment of obligatory
      patellar dislocation in children with ligamentous laxity: a post-operative
      isokinetic study.
AB  - In 11 paediatric patients (seven girls and four boys, from 12 to 15 years old)
      with unilateral obligatory patellar dislocation and ligamentous laxity vastus
      medialis advancement, lateral release, partial patellar ligament transposition
      and Galeazzi semitendinosus tenodesis was undertaken to stabilise the patella.
      The diagnostic criterion for ligamentous laxity was based on the Beighton scale.
      Outcomes were evaluated radiologically and functionally by measurement of the
      range of knee movement and isokinetic testing. The evaluation also included the
      Lysholm knee scale. Follow-up studies took place at a mean of 8.1 years (5 to 15)
      post-operatively. Normal patellar tracking without any recurrence of dislocation
      was obtained in ten out of 11 patients. Pain related to vigorous activity was
      reported by nine patients. Compared with the opposite normal side, the isokinetic
      tests revealed a statistically significant decrease in the maximal torque values
      for the affected quadriceps muscle (p = 0.003 and p = 0.004), but no difference
      between the knee flexors (for angular velocities of 60 degrees /s and 180 degrees
      /s) (p = 0.858 and p = 0.79). The applied surgical technique generally prevents
      the recurrence of the disorder in children with habitual patellar dislocation and
      ligamentous laxity. Quadriceps muscle weakness can be expected to occur post
      operatively.

PMID- 25568427
TI  - The prognostic value of the fracture level in the treatment of Gartland type III
      supracondylar humeral fracture in children.
AB  - A small proportion of children with Gartland type III supracondylar humeral
      fracture (SCHF) experience troubling limited or delayed recovery after operative
      treatment. We hypothesised that the fracture level relative to the isthmus of the
      humerus would affect the outcome. We retrospectively reviewed 230 children who
      underwent closed reduction and percutaneous pinning (CRPP) for their Gartland
      type III SCHFs between March 2003 and December 2012. There were 144 boys and 86
      girls, with the mean age of six years (1.1 to 15.2). The clinico-radiological
      characteristics and surgical outcomes (recovery of the elbow range of movement,
      post-operative angulation, and the final Flynn grade) were recorded. Multivariate
      analysis was employed to identify prognostic factors that influenced outcome,
      including fracture level. Multivariate analysis revealed that a fracture below
      the humeral isthmus was significantly associated with poor prognosis in terms of
      the range of elbow movement (p < 0.001), angulation (p = 0.001) and Flynn grade
      (p = 0.003). Age over ten years was also a poor prognostic factor for recovery of
      the range of elbow movement (p = 0.027). This is the first study demonstrating a
      subclassification system of Gartland III fractures with prognostic significance.
      This will guide surgeons in peri-operative planning and counselling as well as
      directing future research aimed at improving outcomes.

PMID- 25568428
TI  - Capsule repair may reduce dislocation following hip hemiarthroplasty through a
      direct lateral approach: a cadaver study.
AB  - Reported rates of dislocation in hip hemiarthroplasty (HA) for the treatment of
      intra-capsular fractures of the hip, range between 1% and 10%. HA is frequently
      performed through a direct lateral surgical approach. The aim of this study is to
      determine the contribution of the anterior capsule to the stability of a cemented
      HA through a direct lateral approach. A total of five whole-body cadavers were
      thawed at room temperature, providing ten hip joints for investigation. A
      Thompson HA was cemented in place via a direct lateral approach. The cadavers
      were then positioned supine, both knee joints were disarticulated and a digital
      torque wrench was attached to the femur using a circular frame with three half
      pins. The wrench applied an external rotation force with the hip in extension to
      allow the hip to dislocate anteriorly. Each hip was dislocated twice; once with a
      capsular repair and once without repairing the capsule. Stratified sampling
      ensured the order in which this was performed was alternated for the paired hips
      on each cadaver. Comparing peak torque force in hips with the capsule repaired
      and peak torque force in hips without repair of the capsule, revealed a
      significant difference between the 'capsule repaired' (mean 22.96 Nm, standard
      deviation (sd) 4.61) and the 'capsule not repaired' group (mean 5.6 Nm, sd 2.81)
      (p < 0.001). Capsular repair may help reduce the risk of hip dislocation
      following HA.

PMID- 25568429
TI  - Historical perspectives in clinical pathology: a history of glucose measurement.
AB  - This is the second in the series of historical articles dealing with developments
      in clinical pathology. As one of the most commonly measured analytes in
      pathology, the assessment of glucose dates back to the time of the ancient
      Egyptians. It was only in the 19th century that advances in chemistry led to the
      identification of the sugar in urine being glucose. The following century
      witnessed the development of more chemical and enzymatic methods which became
      incorporated into the modern analysers and point-of-care instruments which are as
      ubiquitous as the modern day cellphones. Tracking the milestones in these
      developments shows the striking paradigms and the many parallels in the
      development of other clinical chemistry methods. 

PMID- 25568430
TI  - Use of a culture-independent gastrointestinal multiplex PCR panel during a
      Shigellosis outbreak: considerations for clinical laboratories and public health.

PMID- 25568431
TI  - Validation of a new Aspergillus real-time PCR assay for direct detection of
      Aspergillus and azole resistance of Aspergillus fumigatus on bronchoalveolar
      lavage fluid.
AB  - Azole resistance in Aspergillus fumigatus is increasingly reported. Here, we
      describe the validation of the AsperGenius, a new multiplex real-time PCR assay
      consisting of two multiplex real-time PCRs, one that identifies the clinically
      relevant Aspergillus species, and one that detects the TR34, L98H, T289A, and
      Y121F mutations in CYP51A and differentiates susceptible from resistant A.
      fumigatus strains. The diagnostic performance of the AsperGenius assay was tested
      on 37 bronchoalveolar lavage (BAL) fluid samples from hematology patients and 40
      BAL fluid samples from intensive care unit (ICU) patients using a BAL fluid
      galactomannan level of >=1.0 or positive culture as the gold standard for
      detecting the presence of Aspergillus. In the hematology and ICU groups combined,
      there were 22 BAL fluid samples from patients with invasive aspergillosis (IA) (2
      proven, 9 probable, and 11 nonclassifiable). Nineteen of the 22 BAL fluid samples
      were positive, according to the gold standard. The optimal cycle threshold value
      for the presence of Aspergillus was <36. Sixteen of the 19 BAL fluid samples had
      a positive PCR (2 Aspergillus species and 14 A. fumigatus samples). This resulted
      in a sensitivity, specificity, and positive and negative predictive values of
      88.9%, 89.3%, 72.7%, and 96.2%, respectively, for the hematology group and 80.0%,
      93.3%, 80.0%, and 93.3%, respectively, in the ICU group. The CYP51A real-time PCR
      confirmed 12 wild-type and 2 resistant strains (1 TR34-L98H and 1 TR46-Y121F
      T289A mutant). Voriconazole therapy failed for both patients. The AsperGenius
      multiplex real-time PCR assay allows for sensitive and fast detection of
      Aspergillus species directly from BAL fluid samples. More importantly, this assay
      detects and differentiates wild-type from resistant strains, even if BAL fluid
      cultures remain negative. 

PMID- 25568432
TI  - Four foodborne disease outbreaks caused by a new type of enterotoxin-producing
      Clostridium perfringens.
AB  - The epidemiological and bacteriological investigations on four foodborne
      outbreaks caused by a new type of enterotoxin-producing Clostridium perfringens
      are described. C. perfringens isolated from patients of these outbreaks did not
      produce any known enterotoxin and did not carry the C. perfringens enterotoxin
      gene. However, the culture filtrates of these isolates induced the accumulation
      of fluid in rabbit ileal loop tests. The molecular weight of the new enterotoxin
      may be between 50,000 and 100,000, although the known C. perfringens enterotoxin
      is ca. 35,000. This new enterotoxin was heat labile, and its biological
      activities were inactivated by heating for 5 min at 60 degrees C. The new
      enterotoxin was sensitive to pH values higher than 11.0 and protease treatment
      but was resistant to trypsin treatment. These results suggest that the new
      enterotoxin may be a protein. Although C. perfringens enterotoxin induced
      morphological changes in Vero cells, the changes induced by the new enterotoxin
      differed from those by the known C. perfringens enterotoxin. The new enterotoxin
      also induced morphological changes in L929 cells, whereas the known C.
      perfringens enterotoxin did not, because L929 cells lacked an appropriate
      enterotoxin receptor. Although C. perfringens enterotoxin is recognized as the
      only diarrheagenic toxin responsible for C. perfringens foodborne outbreaks, the
      results of the present study indicate that C. perfringens isolated from these
      four outbreaks produced a new type of enterotoxin. 

PMID- 25568433
TI  - Candida fermentati as a cause of persistent fungemia in a preterm neonate
      successfully treated by combination therapy with amphotericin B and caspofungin.
AB  - A case of persistent candidemia in a preterm neonate caused by Candida
      fermentati, identified by sequencing of the internally transcribed spacer region
      of ribosomal DNA (rDNA), is described. The neonate was treated for 30 days by
      combination therapy with amphotericin B (AmBisome) and caspofungin with a
      successful outcome, and no drug-related side effects were observed. 

PMID- 25568435
TI  - Criteria for reducing unnecessary testing for herpes simplex virus, varicella
      zoster virus, cytomegalovirus, and enterovirus in cerebrospinal fluid samples
      from adults.
AB  - Excessive utilization of laboratory diagnostic testing leads to increased health
      care costs. We evaluated criteria to reduce unnecessary nucleic acid
      amplification testing (NAAT) for viral pathogens in cerebrospinal fluid (CSF)
      samples from adults. This is a single-center split retrospective observational
      study with a screening cohort from 2008 to 2012 and a validation cohort from
      2013. Adults with available results for herpes simplex virus 1/2 (HSV-1/2),
      varicella-zoster virus (VZV), cytomegalovirus (CMV), or enterovirus (EV) NAAT
      with CSF samples between 2008 and 2013 were included (n = 10,917). During this
      study, 1.3% (n = 140) of viral NAAT studies yielded positive results. The
      acceptance criteria of >10 nucleated cells/MUl in the CSF of immunocompetent
      subjects would have reduced HSV-1/2, VZV, CMV, and EV testing by 63%, 50%, 44%,
      and 51%, respectively, from 2008 to 2012. When these criteria were applied to the
      2013 validation data set, 54% of HSV-1/2, 57% of VZV, 35% of CMV, and 56% of EV
      tests would have been cancelled. No clinically significant positive tests would
      have been cancelled in 2013 with this approach. The introduction of a
      computerized order entry set was associated with increased test requests,
      suggesting that computerized order sets may contribute to unnecessary testing.
      Acceptance criteria of >10 nucleated cells/MUl in the CSF of immunocompetent
      adults for viral CSF NAAT assays would increase clinical specificity and preserve
      sensitivity, resulting in significant cost savings. Implementation of these
      acceptance criteria led to a 46% reduction in testing during a limited follow-up
      period. 

PMID- 25568434
TI  - Molecular epidemiological characteristics of Klebsiella pneumoniae associated
      with bacteremia among patients with pneumonia.
AB  - Some important virulence factors have been elucidated in Klebsiella pneumoniae
      infections. We investigated the relationship between virulence factors and
      multilocus sequence types (STs) and assessed the risk factors for bacteremia in
      patients with pneumonia due to K. pneumoniae. From April 2004 through April 2012,
      a total of 120 K. pneumoniae isolates from patients with pneumonia (23 with
      bacteremia and 97 without bacteremia) were collected from 10 medical institutions
      in Japan. Additionally, 10 strains of K. pneumoniae serotype K2 that were
      isolated >30 years ago were included in this study. These isolates were
      characterized using multilocus sequence typing (MLST), and the characteristics of
      their virulence factors, such as hypermucoviscosity phenotype and RmpA and
      aerobactin production between patients with and without bacteremia, were
      examined. MLST analysis was performed on the 120 isolates from patients with
      pneumonia, and some sequence type groups were defined as genetic lineages (GLs).
      GL65 was more prevalent among patients with bacteremia (21.7%) than in those
      without bacteremia (7.2%). The majority of the strains with serotype K2 were
      classified into GL14 or GL65, and rmpA and the gene for aerobactin were present
      in all GL65-K2 strains but absent in all GL14-K2 strains. In a multivariate
      analysis, the independent risk factors for bacteremia included GL65 (adjusted
      odds ratio [AOR], 9.46; 95% confidence interval [CI], 1.81 to 49.31), as well as
      neoplastic disease (AOR, 9.94; 95% CI, 2.61 to 37.92), immunosuppression (AOR,
      17.85; 95% CI, 1.49 to 214.17), and hypoalbuminemia (AOR, 4.76; 95% CI, 1.29 to
      17.61). GL65 was more prevalent among patients with bacteremia and was associated
      with the virulence factors of K. pneumoniae. 

PMID- 25568436
TI  - First case of disseminated infection with Nocardia cerradoensis in a human.
AB  - Here we report in a human, a renal transplant patient, the first disseminated
      infection with Nocardia cerradoensis, isolated after a brain biopsy. Species
      identification was based on 16S rRNA, gyrB, and hsp65 gene analyses. Antibiotic
      treatment was successful by combining carbapenems and aminoglycosides and then
      switching to oral trimethoprim-sulfamethoxazole. 

PMID- 25568437
TI  - Absence of a functional erm gene in isolates of Mycobacterium immunogenum and the
      Mycobacterium mucogenicum group, based on in vitro clarithromycin susceptibility.
AB  - Macrolide resistance has been linked to the presence of a functional erythromycin
      ribosomal methylase (erm) gene in most species of pathogenic rapidly growing
      mycobacteria (RGM). For these Mycobacterium isolates, extended incubation in
      clarithromycin is necessary to determine macrolide susceptibility. In contrast,
      the absence of a detectable erm gene in isolates of M. chelonae, M. senegalense,
      and M. peregrinum and a nonfunctional erm gene in M. abscessus subsp. massiliense
      and 15% to 20% of M. abscessus subsp. abscessus isolates renders these species
      intrinsically macrolide susceptible. Not all RGM species have been screened for
      the presence of an erm gene, including the Mycobacterium mucogenicum group (M.
      mucogenicum, M. phocaicum, and M. aubagnense) and Mycobacterium immunogenum. A
      total of 356 isolates of these two pathogenic RGM taxa from two reference
      laboratories (A.R.U.P. Reference Laboratories and the Mycobacteria/Nocardia
      Laboratory at the University of Texas Health Science Center at Tyler) underwent
      clarithromycin susceptibility testing with readings at 3 to 5 days and 14 days.
      Only 13 of the 356 isolates had resistant clarithromycin MICs at initial extended
      MIC readings, and repeat values on all available isolates were <=2 MUg/ml. These
      studies suggest that these two additional RGM groups do not harbor functional erm
      genes and, like M. chelonae, do not require extended clarithromycin
      susceptibility testing. We propose to the Clinical Laboratory and Standards
      Institute that isolates belonging to these above-mentioned six rapidly growing
      mycobacterial groups based on molecular identification with no known functional
      erm genes undergo only 3 to 5 days of susceptibility testing (to exclude
      mutational resistance). 

PMID- 25568438
TI  - Early detection of dengue virus by use of reverse transcription-recombinase
      polymerase amplification.
AB  - A method for the rapid diagnosis of early dengue virus (DENV) infection is highly
      needed. Here, a prototype reverse transcription-recombinase polymerase
      amplification (RT-RPA) assay was developed. The assay detected DENV RNA in <20
      min without the need for thermocycling amplification. The assay enabled the
      detection of as few as 10 copies of DENV RNA. The designed RT-RPA primers and exo
      probe detected the DENV genome of at least 12 genotypes of DENV circulating
      globally without cross-reacting with other arboviruses. We assessed the
      diagnostic performance of the RT-RPA assay for the detection of DENV RNA in 203
      serum samples of patients with clinically suspected dengue. The sera were
      simultaneously tested for DENV using a reverse transcription-loop-mediated
      isothermal amplification (RT-LAMP) assay, quantitative RT-PCR (qRT-PCR), and IgM-
      and IgG-capture enzyme-linked immunosorbent assays (ELISA). Acute DENV infection
      was confirmed in 130 samples and 61 of the samples (46.9%) were classified as
      viremic with qRT-PCR. The RT-RPA assay showed good concordance (kappa of >=0.723)
      with the RT-LAMP and qRT-PCR assays in detecting the dengue viremic samples. When
      used in combination with ELISA, both the RT-RPA and RT-LAMP assays increased the
      detection of acute DENV infection to >=95.7% (>=45/47) in samples obtained within
      5 days of illness. The results from the study suggest that the RT-RPA assay is
      the most rapid molecular diagnostic tool available for the detection of DENV.
      Hence, it is possible to use the RT-RPA assay in a laboratory to complement
      routine serology testing for dengue. 

PMID- 25568439
TI  - Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii isolates
      in the Gulf Cooperation Council States: dominance of OXA-23-type producers.
AB  - The molecular epidemiology and mechanisms of resistance of carbapenem-resistant
      Acinetobacter baumannii (CRAB) were determined in hospitals in the states of the
      Cooperation Council for the Arab States of the Gulf (Gulf Cooperation Council
      [GCC]), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and
      Kuwait. Isolates were subjected to PCR-based detection of antibiotic resistance
      genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality.
      Selected isolates were subjected to multilocus sequence typing (MLST). We
      investigated 117 isolates resistant to carbapenem antibiotics (either imipenem or
      meropenem). All isolates were positive for OXA-51. The most common carbapenemases
      were the OXA-23-type, found in 107 isolates, followed by OXA-40-type (OXA-24
      type), found in 5 isolates; 3 isolates carried the ISAba1 element upstream of
      blaOXA-51-type. No OXA-58-type, NDM-type, VIM-type, or IMP-type producers were
      detected. Multiple clones were detected with 16 clusters of clonally related
      CRAB. Some clusters involved hospitals in different states. MLST analysis of 15
      representative isolates from different clusters identified seven different
      sequence types (ST195, ST208, ST229, ST436, ST450, ST452, and ST499), as well as
      three novel STs. The vast majority (84%) of the isolates in this study were
      associated with health care exposure. Awareness of multidrug-resistant organisms
      in GCC states has important implications for optimizing infection control
      practices; establishing antimicrobial stewardship programs within hospital,
      community, and agricultural settings; and emphasizing the need for establishing
      regional active surveillance systems. This will help to control the spread of
      CRAB in the Middle East and in hospitals accommodating transferred patients from
      this region. 

PMID- 25568440
TI  - Clinical and molecular epidemiology of Staphylococcus argenteus infections in
      Thailand.
AB  - Molecular typing of 246 Staphylococcus aureus isolates from unselected patients
      in Thailand showed that 10 (4.1%) were actually Staphylococcus argenteus.
      Contrary to the suggestion that S. argenteus is less virulent than S. aureus, we
      demonstrated comparable rates of morbidity, death, and health care-associated
      infection in patients infected with either of these two species. 

PMID- 25568441
TI  - Molecular epidemiology of enterovirus D68 from 2013 to 2014 in Philippines.
AB  - Enterovirus D68 (EV-D68) has been recognized as an important cause of acute
      respiratory infections. Here we report the molecular epidemiology of EV-D68 in
      Philippines from 2013 to 2014; we found cases in areas affected by Typhoon Haiyan
      and found new strains in the country. 

PMID- 25568442
TI  - Studying Bordetella pertussis populations by use of SNPeX, a simple high
      throughput single nucleotide polymorphism typing method.
AB  - Large outbreaks of pertussis occur despite vaccination. A first step in the
      analyses of outbreaks is strain typing. However, the typing of Bordetella
      pertussis, the causative agent of pertussis, is problematic because the available
      assays are insufficiently discriminatory, not unequivocal, time-consuming, and/or
      costly. Here, we describe a single nucleotide primer extension assay for the
      study of B. pertussis populations, SNPeX (single nucleotide primer extension),
      which addresses these problems. The assay is based on the incorporation of
      fluorescently labeled dideoxynucleotides (ddNTPs) at the 3' end of allele
      specific poly(A)-tailed primers and subsequent analysis with a capillary DNA
      analyzer. Each single nucleotide polymorphism (SNP) primer has a specific length,
      and as a result, up to 20 SNPs can be determined in one SNPeX reaction.
      Importantly, PCR amplification of target DNA is not required. We selected 38
      SNPeX targets from the whole-genome sequencing data of 74 B. pertussis strains
      collected from across the world. The SNPeX-based phylogenetic trees preserved the
      general tree topology of B. pertussis populations based on whole-genome
      sequencing, with a minor loss of details. We envisage a strategy whereby SNP
      types (SnpTs) are quickly identified with the SNPeX assay during an outbreak,
      followed by whole-genome sequencing (WGS) of a limited number of isolates
      representing predominant SnpTs and the incorporation of novel SNPs in the SNPeX
      assay. The flexibility of the SNPeX assay allows the method to evolve along with
      the pathogen, making it a promising method for studying outbreaks of B. pertussis
      and other pathogens. 

PMID- 25568443
TI  - Comparison of the genedia MTB detection kit and the cobas TaqMan MTB assay for
      detection of Mycobacterium tuberculosis in respiratory specimens.
AB  - The performance of the Genedia MTB detection kit was compared with that of the
      Cobas TaqMan MTB test using respiratory specimens. The Genedia and Cobas assays
      showed comparable sensitivities (81.8% and 78.8%, respectively) and specificities
      (99.8% and 99.5%, respectively), while the Genedia assay produced fewer invalid
      results and required less turnaround time and labor. 

PMID- 25568445
TI  - Epigenetics in comparative physiology.

PMID- 25568444
TI  - Volatile-sulfur-compound profile distinguishes Burkholderia pseudomallei from
      Burkholderia thailandensis.
AB  - Solid-phase microextraction gas chromatography-mass spectrometry (SPME-GCMS) was
      used to show that dimethyl sulfide produced by Burkholderia pseudomallei is
      responsible for its unusual truffle-like smell and distinguishes the species from
      Burkholderia thailandensis. SPME-GCMS can be safely used to detect dimethyl
      sulfide produced by agar-grown B. pseudomallei. 

PMID- 25568446
TI  - Evolution beyond neo-Darwinism: a new conceptual framework.
AB  - Experimental results in epigenetics and related fields of biological research
      show that the Modern Synthesis (neo-Darwinist) theory of evolution requires
      either extension or replacement. This article examines the conceptual framework
      of neo-Darwinism, including the concepts of 'gene', 'selfish', 'code', 'program',
      'blueprint', 'book of life', 'replicator' and 'vehicle'. This form of
      representation is a barrier to extending or replacing existing theory as it
      confuses conceptual and empirical matters. These need to be clearly
      distinguished. In the case of the central concept of 'gene', the definition has
      moved all the way from describing a necessary cause (defined in terms of the
      inheritable phenotype itself) to an empirically testable hypothesis (in terms of
      causation by DNA sequences). Neo-Darwinism also privileges 'genes' in causation,
      whereas in multi-way networks of interactions there can be no privileged cause.
      An alternative conceptual framework is proposed that avoids these problems, and
      which is more favourable to an integrated systems view of evolution. 

PMID- 25568447
TI  - New insights into mechanisms that regulate DNA methylation patterning.
AB  - From a fertilised egg to a mature organism, cells divide and accumulate
      epigenetic information, which is faithfully passed on to daughter cells. DNA
      methylation consolidates the memory of the developmental history and, albeit very
      stable, it is not immutable and DNA methylation patterns can be deconstructed - a
      process that is essential to regain totipotency. Research into DNA methylation
      erasure gained momentum a few years ago with the discovery of 5
      hydroxymethylcytosine, an oxidation product of 5-methylcytosine. The role of this
      new epigenetic modification in DNA demethylation and other potential epigenetic
      roles are discussed here. But what are the mechanisms that regulate deposition of
      epigenetic modifications? Until recently, limited direct evidence indicated that
      signalling molecules are able to modulate the function of epigenetic modifiers,
      which shape the epigenome in the nucleus of the cell. New reports in embryonic
      stem cell model systems disclosed a tight relationship between major signalling
      pathways and the DNA methylation machinery, which opens up exciting avenues in
      the relationship between external signals and epigenetic memory. Here, I discuss
      mechanisms and concepts in DNA methylation patterning, the implications in normal
      development and disease, and future directions.

PMID- 25568449
TI  - Adding 'epi-' to behaviour genetics: implications for animal domestication.
AB  - In this review, it is argued that greatly improved understanding of domestication
      may be gained from extending the field of behaviour genetics to also include
      epigenetics. Domestication offers an interesting framework of rapid evolutionary
      changes caused by well-defined selection pressures. Behaviour is an important
      phenotype in this context, as it represents the primary means of response to
      environmental challenges. An overview is provided of the evidence for genetic
      involvement in behavioural control and the presently used methods for finding so
      called behaviour genes. This shows that evolutionary changes in behaviour are to
      a large extent correlated to changes in patterns of gene expression, which brings
      epigenetics into the focus. This area is concerned with the mechanisms
      controlling the timing and extent of gene expression, and a lot of focus has been
      placed on methylation of cytosine in promoter regions, usually associated with
      genetic downregulation. The review considers the available evidence that
      environmental input, for example stress, can modify methylation and other
      epigenetic marks and subsequently affect behaviour. Furthermore, several studies
      are reviewed, demonstrating that acquired epigenetic modifications can be
      inherited and cause trans-generational behaviour changes. In conclusion,
      epigenetics may signify a new paradigm in this respect, as it shows that genomic
      modifications can be caused by environmental signals, and random mutations in DNA
      sequence are therefore not the only sources of heritable genetic variation. 

PMID- 25568450
TI  - A review of transgenerational epigenetics for RNAi, longevity, germline
      maintenance and olfactory imprinting in Caenorhabditis elegans.
AB  - Inheritance of acquired characteristics without changes in DNA sequence has been
      called transgenerational epigenetics. This review looks at studies that used the
      model system Caenorhabditis elegans to uncover mechanisms of transgenerational
      epigenetics in studies of RNA interference, studies of longevity, studies of
      germline continuity and a study on olfactory imprinting. In each case,
      researchers have uncovered critical roles for small RNAs and for Argonaute
      proteins. They have revealed several different genetic pathways that mediate RNA
      silencing of foreign RNA for a few or for many generations, as well as
      identifying a related pathway responsible for recognized self-generated RNAs.
      Together, these studies have greatly advanced our understanding of
      trangenerational epigenetics. 

PMID- 25568451
TI  - Placental contribution to nutritional programming of health and diseases:
      epigenetics and sexual dimorphism.
AB  - The recent and rapid worldwide increase in non-communicable diseases challenges
      the assumption that genetic factors are the primary contributors to such
      diseases. A new concept of the 'developmental origins of health and disease'
      (DOHaD) is at stake and therefore requires a paradigm shift. Maternal obesity and
      malnutrition predispose offspring to develop metabolic syndrome, a vicious cycle
      leading to transmission to subsequent generation(s), with differences in response
      and susceptibility according to the sex of the individual. The placenta is a
      programming agent of adult health and disease. Adaptations of placental phenotype
      in response to maternal diet and metabolic status alter fetal nutrient supply.
      This implies important epigenetic changes that are, however, still poorly
      documented in DOHaD studies, particularly concerning overnutrition. The aim of
      this review is to discuss the emerging knowledge on the relationships between the
      effect of maternal nutrition or metabolic status on placental function and the
      risk of diseases later in life, with a specific focus on epigenetic mechanisms
      and sexual dimorphism. Explaining the sex-specific causal variables and how males
      versus females respond and adapt to environmental perturbations should help
      physicians and patients to anticipate disease susceptibility. 

PMID- 25568448
TI  - Epigenetic mechanisms underlying the role of brain-derived neurotrophic factor in
      depression and response to antidepressants.
AB  - Major depressive disorder (MDD) is a devastating neuropsychiatric disorder
      encompassing a wide range of cognitive and emotional dysfunctions. The prevalence
      of MDD is expected to continue its growth to become the second leading cause of
      disease burden (after HIV) by 2030. Despite an extensive research effort, the
      exact etiology of MDD remains elusive and the diagnostics uncertain. Moreover, a
      marked inter-individual variability is observed in the vulnerability to develop
      depression, as well as in response to antidepressant treatment, for nearly 50% of
      patients. Although a genetic component accounts for some cases of MDD, it is now
      clearly established that MDD results from strong gene and environment
      interactions. Such interactions could be mediated by epigenetic mechanisms,
      defined as chromatin and DNA modifications that alter gene expression without
      changing the DNA structure itself. Some epigenetic mechanisms have recently
      emerged as particularly relevant molecular substrates, promoting vulnerability or
      resilience to the development of depressive-like symptoms. Although the role of
      brain-derived neurotrophic factor (BDNF) in the pathophysiology of MDD remains
      unclear, its modulation of the efficacy of antidepressants is clearly
      established. Therefore, in this review, we focus on the epigenetic mechanisms
      regulating the expression of BDNF in humans and in animal models of depression,
      and discuss their role in individual differences in vulnerability to depression
      and response to antidepressant drugs. 

PMID- 25568454
TI  - Dynamics of epigenetic phenomena: intergenerational and intragenerational
      phenotype 'washout'.
AB  - Epigenetic studies of both intragenerational and transgenerational epigenetic
      phenotypic modifications have proliferated in the last few decades. However, the
      strong reductionist focus on mechanism that prevails in many epigenetic studies
      to date has diverted attention away what might be called the 'dynamics' of
      epigenetics and its role in comparative biology. Epigenetic dynamics describes
      how both transgenerational and intragenerational epigenetic phenotypic
      modifications change in non-linear patterns over time. Importantly, a dynamic
      perspective suggests that epigenetic phenomena should not be regarded as
      'digital' (on-off), in which a modified trait necessarily suddenly disappears
      between one generation and the next. Rather, dynamic epigenetic phenomena may be
      better depicted by graded, time-related changes that can potentially involve the
      'washout' of modified phenotype both within and across generations. Conceivably,
      an epigenetic effect might also 'wash-in' over multiple generations, and there
      may be unexplored additive effects resulting from the pressures of environmental
      stressors that wax, wane and then wax again across multiple generations.
      Recognition of epigenetic dynamics is also highly dependent on the threshold for
      detection of the phenotypic modification of interest, especially when phenotypes
      wash out or wash in. Thus, studies of transgenerational epigenetic effects (and
      intragenerational effects, for that matter) that search for persistence of the
      phenomenon are best conducted with highly sensitive, precise quantitative
      methods. All of the scenarios in this review representing epigenetic dynamics are
      possible and some even likely. Focused investigations that concentrate on the
      time course will reveal much about both the impact and mechanisms of epigenetic
      phenomena. 

PMID- 25568455
TI  - Epigenetics and locust life phase transitions.
AB  - Insects are one of the most successful classes on Earth, reflected in an enormous
      species richness and diversity. Arguably, this success is partly due to the high
      degree to which polyphenism, where one genotype gives rise to more than one
      phenotype, is exploited by many of its species. In social insects, for instance,
      larval diet influences the development into distinct castes; and locust
      polyphenism has tricked researchers for years into believing that the drastically
      different solitarious and gregarious phases might be different species.
      Solitarious locusts behave much as common grasshoppers. However, they are
      notorious for forming vast, devastating swarms upon crowding. These gregarious
      animals are shorter lived, less fecund and transmit their phase characteristics
      to their offspring. The behavioural gregarisation occurs within hours, yet the
      full display of gregarious characters takes several generations, as does the
      reversal to the solitarious phase. Hormones, neuropeptides and neurotransmitters
      influence some of the phase traits; however, none of the suggested mechanisms can
      account for all the observed differences, notably imprinting effects on longevity
      and fecundity. This is why, more recently, epigenetics has caught the interest of
      the polyphenism field. Accumulating evidence points towards a role for epigenetic
      regulation in locust phase polyphenism. This is corroborated in the economically
      important locust species Locusta migratoria and Schistocerca gregaria. Here, we
      review the key elements involved in phase transition in locusts and possible
      epigenetic regulation. We discuss the relative role of DNA methylation, histone
      modification and small RNA molecules, and suggest future research directions. 

PMID- 25568456
TI  - Natural epigenetic variation in bats and its role in evolution.
AB  - When facing the challenges of environmental change, such as habitat
      fragmentation, organisms have to adjust their phenotype to adapt to various
      environmental stresses. Recent studies show that epigenetic modifications could
      mediate environmentally induced phenotypic variation, and this epigenetic
      variance could be inherited by future generations, indicating that epigenetic
      processes have potential evolutionary effects. Bats living in diverse
      environments show geographic variations in phenotype, and the females usually
      have natal philopatry, presenting an opportunity to explore how environments
      shape epigenetic marks on the genome and the evolutionary potential of epigenetic
      variance in bat populations for adaptation. We have explored the natural
      epigenetic diversity and structure of female populations of the great roundleaf
      bat (Hipposideros armiger), the least horseshoe bat (Rhinolophus pusillus) and
      the eastern bent-winged bat (Miniopterus fuliginosus) using a methylation
      sensitive amplified polymorphism technique. We have also estimated the effects of
      genetic variance and ecological variables on epigenetic diversification. All
      three bat species have a low level of genomic DNA methylation and extensive
      epigenetic diversity that exceeds the corresponding genetic variance. DNA
      sequence divergence, epigenetic drift and environmental variables contribute to
      the epigenetic diversities of each species. Environment-induced epigenetic
      variation may be inherited as a result of both mitosis and meiosis, and their
      potential roles in evolution for bat populations are also discussed in this
      review. 

PMID- 25568452
TI  - Epigenetic linkage of aging, cancer and nutrition.
AB  - Epigenetic mechanisms play a pivotal role in the expression of genes and can be
      influenced by both the quality and quantity of diet. Dietary compounds such as
      sulforaphane (SFN) found in cruciferous vegetables and epigallocatechin-3-gallate
      (EGCG) in green tea exhibit the ability to affect various epigenetic mechanisms
      such as DNA methyltransferase (DNMT) inhibition, histone modifications via
      histone deacetylase (HDAC), histone acetyltransferase (HAT) inhibition, or
      noncoding RNA expression. Regulation of these epigenetic mechanisms has been
      shown to have notable influences on the formation and progression of various
      neoplasms. We have shown that an epigenetic diet can influence both cellular
      longevity and carcinogenesis through the modulation of certain key genes that
      encode telomerase and p16. Caloric restriction (CR) can also play a crucial role
      in aging and cancer. Reductions in caloric intake have been shown to increase
      both the life- and health-span in a variety of animal models. Moreover,
      restriction of glucose has been demonstrated to decrease the incidence of age
      related diseases such as cancer and diabetes. A diet rich in compounds such as
      genistein, SFN and EGCG can positively modulate the epigenome and lead to many
      health benefits. Also, reducing the quantity of calories and glucose in the diet
      can confer an increased health-span, including reduced cancer incidence. 

PMID- 25568457
TI  - Environmentally induced (co)variance in sperm and offspring phenotypes as a
      source of epigenetic effects.
AB  - Traditionally, it has been assumed that sperm are a vehicle for genes and nothing
      more. As such, the only source of variance in offspring phenotype via the
      paternal line has been genetic effects. More recently, however, it has been shown
      that the phenotype or environment of fathers can affect the phenotype of
      offspring, challenging traditional theory with implications for evolution,
      ecology and human in vitro fertilisation. Here, I review sources of non-genetic
      variation in the sperm phenotype and evidence for co-variation between sperm and
      offspring phenotypes. I distinguish between two environmental sources of
      variation in sperm phenotype: the pre-release environment and the post-release
      environment. Pre-release, sperm phenotypes can vary within species according to
      male phenotype (e.g. body size) and according to local conditions such as the
      threat of sperm competition. Post-release, the physicochemical conditions that
      sperm experience, either when freely spawned or when released into the female
      reproductive tract, can further filter or modify sperm phenotypes. I find
      evidence that both pre- and post-release sperm environments can affect offspring
      phenotype; fertilisation is not a new beginning - rather, the experiences of
      sperm with the father and upon release can drive variation in the phenotype of
      the offspring. Interestingly, there was some evidence for co-variation between
      the stress resistance of sperm and the stress resistance of offspring, though
      more studies are needed to determine whether such effects are widespread.
      Overall, it appears that environmentally induced covariation between sperm and
      offspring phenotypes is non-negligible and further work is needed to determine
      their prevalence and strength.

PMID- 25568453
TI  - Influence of environmental exposure on human epigenetic regulation.
AB  - Environmental toxicants can alter epigenetic regulatory features such as DNA
      methylation and microRNA expression. As the sensitivity of epigenomic regulatory
      features may be greatest during the in utero period, when critical windows are
      narrow, and when epigenomic profiles are being set, this review will highlight
      research focused on that period. I will focus on work in human populations, where
      the impact of environmental toxicants in utero, including cigarette smoke and
      toxic trace metals such as arsenic, mercury and manganese, on genome-wide, gene
      specific DNA methylation has been assessed. In particular, arsenic is
      highlighted, as this metalloid has been the focus of a number of studies and its
      detoxification mechanisms are well understood. Importantly, the tissues and cells
      being examined must be considered in context in order to interpret the findings
      of these studies. For example, by studying the placenta, it is possible to
      identify potential epigenetic adaptations of key genes and pathways that may
      alter the developmental course in line with the developmental origins of health
      and disease paradigm. Alternatively, studies of newborn cord blood can be used to
      examine how environmental exposure in utero can impact the composition of cells
      within the peripheral blood, leading to immunological effects of exposure. The
      results suggest that in humans, like other vertebrates, there is a susceptibility
      for epigenomic alteration by the environment during intrauterine development, and
      this may represent a mechanism of plasticity of the organism in response to its
      environment as well as a mechanism through which long-term health consequences
      can be shaped. 

PMID- 25568459
TI  - The developmental origins of chronic physical aggression: biological pathways
      triggered by early life adversity.
AB  - Longitudinal epidemiological studies with birth cohorts have shown that physical
      aggression in humans does not appear suddenly in adolescence as commonly thought.
      In fact, physically aggressive behaviour is observed as early as 12 months after
      birth, its frequency peaks around 2-4 years of age and decreases in frequency
      until early adulthood. However, a minority of children (3-7%) maintain a high
      frequency of physical aggression from childhood to adolescence and develop
      serious social adjustment problems during adulthood. Genetic factors and early
      social experiences, as well as their interaction, have been shown to play an
      important role in the development of chronic aggressive behaviour. However, the
      biological mechanisms underlying these associations are just beginning to be
      uncovered. Recent evidence suggests that epigenetic mechanisms are responsive to
      adverse environments and could be involved in the development of chronic
      aggression. Using both gene candidate and genomic approaches, recent studies have
      identified epigenetic marks, such as DNA methylation alterations in genes
      involved in the stress response and the serotonin and immune systems to be partly
      responsible for the long-lasting effects of early adversity. Further longitudinal
      studies with biological, environmental and behavioural assessments from birth
      onwards are needed to elucidate the sequence of events that leads to these long
      lasting epigenetic marks associated with early adversity and aggression. 

PMID- 25568460
TI  - Twin methodology in epigenetic studies.
AB  - Since the final decades of the last century, twin studies have made a remarkable
      contribution to the genetics of human complex traits and diseases. With the
      recent rapid development in modern biotechnology of high-throughput genetic and
      genomic analyses, twin modelling is expanding from analysis of diseases to
      molecular phenotypes in functional genomics especially in epigenetics, a thriving
      field of research that concerns the environmental regulation of gene expression
      through DNA methylation, histone modification, microRNA and long non-coding RNA
      expression, etc. The application of the twin method to molecular phenotypes
      offers new opportunities to study the genetic (nature) and environmental
      (nurture) contributions to epigenetic regulation of gene activity during
      developmental, ageing and disease processes. Besides the classical twin model,
      the case co-twin design using identical twins discordant for a trait or disease
      is becoming a popular and powerful design for epigenome-wide association study in
      linking environmental exposure to differential epigenetic regulation and to
      disease status while controlling for individual genetic make-up. It can be
      expected that novel uses of twin methods in epigenetic studies are going to help
      with efficiently unravelling the genetic and environmental basis of epigenomics
      in human complex diseases. 

PMID- 25568458
TI  - The expanding epigenetic landscape of non-model organisms.
AB  - Epigenetics studies the emergence of different phenotypes from a single genotype.
      Although these processes are essential to cellular differentiation and
      transcriptional memory, they are also widely used in all branches of the tree of
      life by organisms that require plastic but stable adaptation to their physical
      and social environment. Because of the inherent flexibility of epigenetic
      regulation, a variety of biological phenomena can be traced back to evolutionary
      adaptations of few conserved molecular pathways that converge on chromatin. For
      these reasons chromatin biology and epigenetic research have a rich history of
      chasing discoveries in a variety of model organisms, including yeast, flies,
      plants and humans. Many more fascinating examples of epigenetic plasticity lie
      outside the realm of model organisms and have so far been only sporadically
      investigated at a molecular level; however, recent progress on sequencing
      technology and genome editing tools have begun to blur the lines between model
      and non-model organisms, opening numerous new avenues for investigation. Here, I
      review examples of epigenetic phenomena in non-model organisms that have emerged
      as potential experimental systems, including social insects, fish and flatworms,
      and are becoming accessible to molecular approaches. 

PMID- 25568461
TI  - Neurogenomic mechanisms of social plasticity.
AB  - Group-living animals must adjust the expression of their social behaviour to
      changes in their social environment and to transitions between life-history
      stages, and this social plasticity can be seen as an adaptive trait that can be
      under positive selection when changes in the environment outpace the rate of
      genetic evolutionary change. Here, we propose a conceptual framework for
      understanding the neuromolecular mechanisms of social plasticity. According to
      this framework, social plasticity is achieved by rewiring or by biochemically
      switching nodes of a neural network underlying social behaviour in response to
      perceived social information. Therefore, at the molecular level, it depends on
      the social regulation of gene expression, so that different genomic and
      epigenetic states of this brain network correspond to different behavioural
      states, and the switches between states are orchestrated by signalling pathways
      that interface the social environment and the genotype. Different types of social
      plasticity can be recognized based on the observed patterns of inter- versus
      intra-individual occurrence, time scale and reversibility. It is proposed that
      these different types of social plasticity rely on different proximate mechanisms
      at the physiological, neural and genomic level. 

PMID- 25568462
TI  - Regulation of hypometabolism: insights into epigenetic controls.
AB  - For many animals, survival of severe environmental stress (e.g. to extremes of
      heat or cold, drought, oxygen limitation, food deprivation) is aided by entry
      into a hypometabolic state. Strong depression of metabolic rate, often to only 1
      20% of normal resting rate, is a core survival strategy of multiple forms of
      hypometabolism across the animal kingdom, including hibernation, anaerobiosis,
      aestivation and freeze tolerance. Global biochemical controls are needed to
      suppress and reprioritize energy use; one such well-studied control is reversible
      protein phosphorylation. Recently, we turned our attention to the idea that
      mechanisms previously associated mainly with epigenetic regulation can also
      contribute to reversible suppression of gene expression in hypometabolic states.
      Indeed, situations as diverse as mammalian hibernation and turtle anoxia
      tolerance show coordinated changes in histone post-translational modifications
      (acetylation, phosphorylation) and activities of histone deacetylases, consistent
      with their use as mechanisms for suppressing gene expression during
      hypometabolism. Other potential mechanisms of gene silencing in hypometabolic
      states include altered expression of miRNAs that can provide post-transcriptional
      suppression of mRNA translation and the formation of ribonuclear protein bodies
      in the nucleus and cytoplasm to allow storage of mRNA transcripts until animals
      rouse themselves again. Furthermore, mechanisms first identified in epigenetic
      regulation (e.g. protein acetylation) are now proving to apply to many central
      metabolic enzymes (e.g. lactate dehydrogenase), suggesting a new layer of
      regulatory control that can contribute to coordinating the depression of
      metabolic rate. 

PMID- 25568463
TI  - Thermodynamics Study of Solvent Adsorption on Octadecyl-Modified Silica.
AB  - Elution and solvation processes in liquid chromatography may be controlled by
      temperature changes. In the case of solvent adsorption, the temperature
      influences the amount of adsorbed solvent as well as the enthalpy and entropy of
      the solvation process. In this work, the thermodynamic parameters of organic
      solvents used as organic modifiers in the reversed-phase high-performance liquid
      chromatography elution process were determined. The changes of enthalpy and
      entropy in a series of chemically bonded stationary phases were measured to
      determine the effects of the temperature and surface coverage density of
      octadecyl ligands on the thermodynamic parameters of the solvation. For both the
      enthalpy and entropy a parabolic trend was observed with the minimum for medium
      surface coverage. The correlation of solvent adsorption values with the enthalpy
      of solvation was also investigated. The highest influence of the temperature on
      solvation process was observed for stationary phases with high surface coverage.

PMID- 25568464
TI  - Explanation and Use of the Rio 2011 Colposcopy Nomenclature of the IFCPC
      (International Federation for Cervical Pathology and Colposcopy): Comments on the
      general colposcopic assessment of the uterine cervix: adequate/inadequate;
      squamocolumnar junction; transformation zone.
AB  - In July 2012 the IFCPC adopted a revised terminology for colposcopic examinations
      of the uterine cervix. In 2012, the Boards of the Arbeitsgemeinschaft Kolposkopie
      (AGK - Austrian Society of Colposcopy), the Arbeitsgemeinschaft fur Kolposkopie
      und Zervixpathologie (AGKOL - Swiss Society of Colposcopy and Cervical Pathology)
      and the Arbeitsgemeinschaft fur Kolposkopie und Zervixpathologie (AGCPC - German
      Society of Colposcopy and Cervical Pathology) accepted the validity of the 2011
      IFCPC nomenclature and recommended its use in general clinical practice across
      German-speaking countries. The revised nomenclature was devised so that examiners
      can evaluate colposcopic criteria according to a specific scheme. At the start of
      the examination, the examiner must assess whether the colposcopy is
      representative or not. 1. Can the examination be classed as adequate or
      inadequate (reasons must be given)? 2. How would you describe the visibility of
      the squamocolumnar junction and categorize the transformation zone? Below we
      discuss some aspects of this general assessment as outlined in the nomenclature
      which were found to require further clarification for general practice.

PMID- 25568465
TI  - Interdisciplinary S2k Guideline: Sonography in Urogynecology: Short Version -
      AWMF Registry Number: 015/055.

PMID- 25568466
TI  - Gynaecology - Quo vadis? Situation Analysis, National and International
      Perspectives.
AB  - In a large and heavily networked specialty like gynaecology it is a particular
      challenge with regard to future status to achieve excellent patient care,
      research and teaching. At the same time not only hospitals but also research
      facilities are experiencing increasing pressure from performance and competition
      sides in terms of survival and further development on the clinical, scientific
      and economic fronts. The numerous changes, including paradigm shifts, in
      medicine, society, the health-care system and scientific innovations present new
      challenges to the specialty. This leads to questions about priority, problem
      areas and weaknesses as well as to new opportunities for the field and the
      overall question if it will be possible to meet the paradigm shifts and problems
      by the creation of new structures. In the light of the need for and the potential
      of design measures, this article presents a SWOT analysis of the specialty's
      situation as a whole and in particular for gynaecology in German universities.
      One sees additional demands that add up to an expansion of the tasks. At the same
      time the shortage of new recruits becomes apparent. A broadening of the
      perspectives on women's health and individualised medicine come into focus.
      Partial solutions include new supporting structures, capacity measurements as
      well as even structural options. In particular, the department structure, that is
      common abroad, opens an opportunity for specialisation while maintaining unity
      for a broader further training and strengthened research. Chances and strengths
      of the specialty are especially effective in coordinated and concerted
      activities.

PMID- 25568467
TI  - Influence of Patient and Hospital Characteristics on the Performance of Direct
      Reconstruction after Mastectomy.
AB  - Aim: International studies have shown that the performance of a direct (or
      immediate) reconstruction (DR) after mastectomy is associated with patient (e.g.,
      socio-economic status, insurance status, age) and hospital (number of cases,
      teaching status) characteristics. The present article addresses the question if
      such relationships also exist in Germany. Material and Methods: The results of a
      nationwide questionnaire to the patients of certified breast cancer centres were
      coupled with the clinical features of the patients and the characteristics of the
      hospital. Predictors for receiving a DR (vs. delayed or no reconstruction) were
      estimated by means of a logistic multilevel model for a sample of 1165 patients
      from 105 certified locations. Results: Substantial differences between the
      treating hospitals were found (intraclass correlation coefficient null model:
      0.195) which can in part be explained by the total model (total model: 0.169).
      Patients with the following features are more likely to receive a DR: younger
      age, private health insurance, secondary school leaving certificate (vs. primary
      school leaving certificate), lower stage and acquisition of more information
      about reconstruction. ASA and partnership status are not statistically
      significantly related with DR. DR is more likely to be performed in hospitals
      with higher caseload of patients with primary breast cancer. Teaching status,
      operations per surgeon and urbanity of the location are not related to receiving
      a DR. Conclusions: Non-clinical features of the patients and the primary case
      number are associated with the performance of a DR, this poses questions
      concerning reasons and the equality of health care.

PMID- 25568469
TI  - Indian Journal of Psychiatry: Changes in instructions to contributors.

PMID- 25568470
TI  - The Mental Health Care Bill 2013: A step leading to exclusion of psychiatry from
      the mainstream medicine?

PMID- 25568468
TI  - Evaluation of Therapy Management and Patient Compliance in Postmenopausal
      Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole
      Treatment: The EvaluateTM Study.
AB  - Introduction: The EvaluateTM study (Evaluation of therapy management and patient
      compliance in postmenopausal hormone receptor-positive breast cancer patients
      receiving letrozole treatment) is a prospective, non-interventional study for the
      assessment of therapy management and compliance in the routine care of
      postmenopausal women with invasive hormone receptor-positive breast cancer
      receiving letrozole. The parameters for inclusion in the study are presented and
      discussed here. Material and Methods: Between January 2008 and December 2009 a
      total of 5045 patients in 310 study centers were recruited to the EvaluateTM
      study. Inclusion criteria were hormone receptor-positive breast cancer and
      adjuvant treatment or metastasis. 373 patients were excluded from the analysis
      for various reasons. Results: A total of 4420 patients receiving adjuvant
      treatment and 252 patients with metastasis receiving palliative treatment were
      included in the study. For 4181 patients receiving adjuvant treatment, treatment
      with the aromatase inhibitor letrozole commenced immediately after surgery
      (upfront). Two hundred patients had initially received tamoxifen and started
      aromatase inhibitor treatment with letrozole at 1-5 years after diagnosis
      (switch), und 39 patients only commenced letrozole treatment 5-10 years after
      diagnosis (extended endocrine therapy). Patient and tumor characteristics were
      within expected ranges, as were comorbidities and concurrent medication.
      Conclusion: The data from the EvaluateTM study will offer a good overview of
      therapy management in the routine care of postmenopausal women with hormone
      receptor-positive breast cancer. Planned analyses will look at therapy compliance
      and patient satisfaction with how information is conveyed and the contents of the
      conveyed information.

PMID- 25568471
TI  - Hallucinations in the classical Indian system of Ayurveda: A brief overview.
AB  - The ancient Indian system of medicine "Ayurveda" is a compendium of various
      health related theories and practices and explained the abnormal state of mind,
      i.e., psychopathology in various contexts. Hallucinations were deemed abnormal.
      In Ayurvedic classics, hallucinations were called false perceptions
      (mithyajnana), illusions (maya), infatuations (moha), or confusion (bhrama).
      Hallucinations were not independent but a symptom of mental disorder (manasa
      roga). Hallucinations of different sensory organs were observed and explained.
      These symptoms could be observed in patients suffering from any illness of
      tridosha origin, organic disease or psychiatric disorder. False perceptions
      observed in patients were used as tools to understand the prognosis of the
      condition. This article may help provide preliminary insight and encourage
      interdisciplinary study toward understanding one of the main symptoms of
      schizophrenia. 

PMID- 25568472
TI  - Determinants of symptom profile and severity of conduct disorder in a tertiary
      level pediatric care set up: A pilot study.
AB  - BACKGROUND: Conduct disorders (CDs) are one of the most common causes for
      referral to child and adolescent mental health centers. CD varies in its
      environmental factors, symptom profile, severity, co-morbidity, and functional
      impairment. AIMS: The aim was to analyze the determinants of symptom profile and
      severity among childhood and adolescent onset CD. SETTINGS AND DESIGN: Clinic
      based study with 60 consecutive children between 6 and 18 years of age satisfying
      International Classification of Disease-10 Development Control Rules guidelines
      for CD, attending behavioral pediatrics unit outpatient. MATERIALS AND METHODS:
      The family psychopathology, symptom severity, and functional level were assessed
      using parent interview schedule, revised behavioral problem checklist and
      Children's Global Assessment Scale. STATISTICAL ANALYSIS: The correlation and
      predictive power of the variables were analyzed using SPSS 16.0 version. RESULTS:
      There was significant male dominance (88.3%) with boy girl ratio 7.5:1. Most
      common comorbidity noticed was hyperkinetic disorders (45%). Childhood onset
      group was more predominant (70%). Prevalence of comorbidity was more among early
      onset group (66.7%) than the late-onset group (33.3%). The family
      psychopathology, symptom severity, and the functional impairment were
      significantly higher in the childhood onset group. CONCLUSION: The determinants
      of symptom profile and severity are early onset (childhood onset CD), nature, and
      quantity of family psychopathology, prevalence, and type of comorbidity and
      nature of symptom profile itself. The family psychopathology is positively
      correlated with the symptom severity and negatively correlated with the
      functional level of the children with CD. The symptom severity was negatively
      correlated with the functional level of the child with CD.

PMID- 25568473
TI  - Scale for assessment of lethality of suicide attempt.
AB  - BACKGROUND: Lethality of suicidal attempt provides useful information regarding
      the behavior. There is a perceived need for a clinically useful scale that can be
      easily adapted to various methods and circumstances of attempt. AIMS: The study
      intended to develop and test utility of a scale for measuring lethality that can
      reflect overall clinical observation taking into account various indicators of
      lethality and which can be used across clinical scenarios involving different
      methods. SETTINGS AND DESIGN: Cross-sectional study in a hospital. MATERIALS AND
      METHODS: The scale for assessment of lethality of suicide attempt (SALSA) has two
      components: The first component has four items indicating seriousness of the
      attempt and its likely consequences and the second component is the global
      impression of lethality. All the items are scored from 1 to 5, higher scores
      suggestive of increased lethality. SALSA was used to evaluate lethality of 82
      consecutive suicide attempters; and it was compared with lethality of suicide
      attempt rating scale (LSARS) and risk-rescue rating scale. STATISTICAL ANALYSIS:
      Chi-square, t-test, analysis of variance, Cronbach's alpha, binary logistic
      regression. RESULT: There was significant correlation of SALSA score with that of
      LSARS (r: 0.89) and risk score of risk-rescue rating (r: 0.93, P < 0.001); and
      negative correlation with rescue score (r: -0.569; P < 0.001). Internal
      consistency reliability of SALSA was high (Cronbach's alpha: 0.94). Lethality
      scores of SALSA differentiated known groups with different lethality, e.g.
      deceased and survived; attempters with different levels of medical intervention:
      In-patient only, intensive care, ventilator support. SALSA score significantly
      predicted the lethal outcome (odds ratio: 3.2, confidence interval: 1.12-8.98).
      CONCLUSION: SALSA is a useful instrument for assessment of lethality of suicidal
      behaviors during clinical evaluations considering the ease of administration, its
      ability to differentiate clinical groups with known variations of lethality and
      clinical outcomes.

PMID- 25568475
TI  - Indian Psychiatric Society-World Psychiatric Association - World Health
      Organization survey on usefulness of International Classification of Diseases-10.
AB  - BACKGROUND: World Health Organization (WHO) is in the process of revising the
      International Classification of Diseases 10 (ICD-10). For increasing the
      acceptability of the ICD-11, WHO along with World Psychiatric Association (WPA),
      conducted a survey of psychiatrists around the world, in which 386 psychiatrists
      from India participated. AIM: To present the findings of "WPA-WHO Global Survey
      of Psychiatrists' Attitudes toward Mental Disorders Classification" for Indian
      psychiatrists who participated in the survey as members of Indian Psychiatric
      Society. METHODOLOGY: The online survey was sent to qualified psychiatrists who
      are members of Indian Psychiatric Society and are residing in India. RESULTS: Of
      the 1702 members who were urged to participate in the survey, 386 (22.7%)
      participated. Most(79%) of the psychiatrists opined that they use formal
      classificatory systems in their day-to-day clinical practice. ICD-10 was the most
      commonly (71%) followed classificatory system. Nearly half (48%) felt the need
      for only 10-30 categories for use in clinical settings and another 44% opined
      that 31-100 categories are required for use. Most of the participants (85%)
      suggested that a modified/simpler classificatory system should be designed for
      primary care practitioners. Similarly, the same number of participants (89%)
      argued that for maximum utility of a nosological system diagnostic criteria
      should provide flexible guidance that allows cultural variation and clinical
      judgement. About 75% opined that the diagnostic system they were using was
      difficult to apply across cultures. CONCLUSION: Findings of the survey suggest
      that classificatory systems are routinely used in day-to-day practice by most of
      the participating psychiatrists in India and most expect that future
      classificatory system should provide flexible guidance that allows cultural
      variation and clinical judgement.

PMID- 25568474
TI  - Oxidative stress and level of antioxidant enzymes in drug-naive schizophrenics.
AB  - BACKGROUND: Schizophrenia is a chronic illness having varied etiology which
      affects cognition, emotion, perception, and other aspects of behavior. There are
      data which show possible role of oxidative stress and disturbance in antioxidant
      mechanisms in various neurological and neuropsychiatric disorders. MATERIALS AND
      METHODS: Fifty drug-naive schizophrenic patients, who attended psychiatry
      outpatient department/inpatient department for the 1(st) time, were selected and
      compared with 50 age-sex matched healthy controls. The erythrocyte level of
      malondialdehyde (MDA) - a lipid peroxidation product and marker of oxidative
      stress, antioxidant enzymes - superoxide dismutase (SOD), glutathione peroxidase
      (GPX) was estimated. We also correlated the sociodemographic parameters and
      severity of illness (positive and negative syndrome scale score) with oxidative
      stress (MDA) and level of antioxidant enzymes (SOD, GPX). RESULTS: The level of
      oxidative stress (MDA) was increased, and the levels of antioxidative enzymes
      (GPX and SOD) were decreased in schizophrenic patients as compared to normal
      healthy controls and the difference was statistically significant. No significant
      relationships of age, sex, educational status, marital status, and PANNS score
      with oxidative stress (MDA) and antioxidative enzymes (GPX and SOD) level in
      schizophrenic patients was found; but there was significant relationship of
      locality with oxidative stress (MDA) and antioxidative enzymes (GPX and SOD)
      level in schizophrenic patients was found. Urban population have a higher level
      of MDA, GPX, and SOD than the rural population. CONCLUSION: Our findings put
      great emphasis on the weak pro/antioxidant defense mechanisms and its role in the
      pathophysiology of schizophrenia. We can make recommendations of dietary
      nutritional supplementation and adjunct antioxidants therapy with antipsychotics
      to treat schizophrenics.

PMID- 25568476
TI  - T102C polymorphism of serotonin-2A receptor gene in Turkish schizophrenia
      patients: Association with cognitive impairment and soft neurological signs.
AB  - AIM: Previous studies have shown an association between the T102C polymorphism of
      the serotonin-2A receptor gene and schizophrenia. In addition, an association of
      this polymorphism with clinical phenotypes in schizophrenia such as treatment
      response and cognitive impairment has been observed. MATERIALS AND METHODS: In
      this case-control study conducted in Turkish Caucasians, we compared T102C
      polymorphism genotype and allele frequencies in 76 schizophrenic patients and 165
      healthy controls. We also investigated interaction of this polymorphism with
      clinical and cognitive variables in patients. RESULTS: No significant difference
      was observed in the distribution of the three genotypes (T/T, T/C and C/C) and in
      the allele frequencies in controls and patients with schizophrenia. No evidence
      of association was detected at various clinical phenotypes including symptom
      severity, suicidality, treatment response, age of disease onset, number of
      hospitalizations and history of violence (in co-dominant, dominant, or recessive
      models). However, as compared to the C/C genotype, patients with 1 or 2 copies of
      the T allele were characterized by better stroop test performances and less
      "motor coordination" soft neurological signs. CONCLUSION: Further research is
      needed to elucidate the impact of T102C polymorphism on neurocognitive functions
      in both healthy and patient populations.

PMID- 25568477
TI  - A clinico-epidemiological study of cognitive function status of community
      dwelling elderly.
AB  - BACKGROUND: Cognitive decline and dementia are an important problem affecting
      quality-of-life in elderly and their caregivers. There is regional variation in
      prevalence of cognitive decline as well as risk factors from region to region.
      AIM: The aim was to determine the prevalence of dementia and cognitive decline
      and its various risk factors in the elderly population of more than 60 years in
      Eastern Uttar Pradesh (India). MATERIALS AND METHODS: A camp-based study was
      conducted on rural population of Chiraigaon block of Varanasi district from
      February 2007 to May 2007. Block has 80 villages, of which 11 villages were
      randomly selected. Eleven camps were organized for elderly people in 11 randomly
      selected villages on predetermined dates. A total of 728 elderly persons of age
      >60 years were examined, interviewed and data thus collected was analyzed.
      Elderly who got Hindi-mini-mental state examination (HMSE) score developed by
      Ganguli based on the Indo-US Cross-National Dementia Epidemiology Study) score
      <=23 were evaluated further and in those with confirmed cognitive and functional
      impairment, diagnosis of dementia was assigned according to Diagnostic and
      Statistical Manual for Mental Disorder fourth edition criteria after ruling out
      any psychiatric illness or delirium. Based on International Classification of
      Diseases-10 diagnostic criteria sub-categorization of dementia was done. RESULTS:
      Mean, median and 10(th) percentile of HMSE of the study population were 23.4, 24
      and 17, respectively. About 14.6% elderly had scored <17. 42.9% of rural elderly
      population had HMSE score <23, 70.6% <27 and 27.7% between 23 and 27. Literate
      people had statistically significant higher mean HMSE score (26.1 +/- 3.9) than
      illiterate people (22.9 +/- 4.9). Other risk factors were female gender,
      malnutrition, and obesity. Prevalence of dementia was 2.74%; in male 2.70% and in
      female 2.80%. Most common type of dementia was Alzheimer (male 1.5%, female 1.5%)
      followed by vascular (male 1.2%, female 0.6%) and others 0.6% (male 0%, female
      0.6%). CONCLUSIONS: Study showed that a very high percentage of rural elderly
      attending health camps had poor cognitive function score; though the prevalence
      of dementia was relatively low. Alzheimer dementia was most common, followed by
      vascular dementia, which was predominant in males. Illiteracy, age, and under
      nutrition were the most important risk factors for poor cognitive function. Our
      study suggest that cut-off of HMSE score should be 17 (10(th) percentile) for
      illiterate population.

PMID- 25568480
TI  - Depression versus you.

PMID- 25568478
TI  - Cardiac risk factors and metabolic syndrome in patients with schizophrenia
      admitted to a general hospital psychiatric unit.
AB  - OBJECTIVE: The study aimed to evaluate the prevalence of cardiovascular risk
      (CVR) factors and metabolic syndrome (MS) in patients with schizophrenia.
      MATERIALS AND METHODS: By consecutive sampling, 143 patients (of age >= 20
      years), out of total 159 patients with schizophrenia admitted to the inpatient
      unit were evaluated for the coronary heart disease (CHD) risk as per Framingham
      (10-year all CHD events) function/risk equation and systematic coronary risk
      evaluation (SCORE) - 10-year cardiovascular mortality risk (CMR). Prevalence of
      MS was estimated by using the consensus definition. RESULTS: Fifty-two (36.4%)
      patients fulfilled the criteria for MS. 10-year CHD risk was 1.65%, and 10-year
      CMR was 1.39%. Compared to females, males had higher Framingham score (1.96 +/-
      2.74 vs. 1.09 +/- 0.41, U value 1987.5*, P < 0.05). CONCLUSION: Patients of
      schizophrenia have a high prevalence of MS and CVR factors. Hence, there is a
      need to screen the patient of schizophrenia for the same and manage the same as
      early as possible during the course of illness.

PMID- 25568481
TI  - Relational enmeshment of entangled minds!

PMID- 25568479
TI  - Indian story on semen loss and related Dhat syndrome.
AB  - India is a country of many religions and ancient cultures. Indian culture is
      largely directed by the Vedic culture since time immemorial. Later Indian culture
      is influenced by Buddhism, Islam, and Christianity. Indian belief system carries
      the footprints of these cultures. Every culture describes human behaviors and an
      interpretation of each human behavior is largely influenced by the core cultural
      belief system. Sexuality is an important domain which is colored by different
      cultural colors. Like other cultures, Indian culture believes "semen" as the
      precious body fluid which needs to be preserved. Most Indian beliefs consider
      loss of semen as a threat to the individual. Ancient Indian literature present
      semen loss as a negative health related event. Dhat syndrome (related to semen
      loss) is a culture-bound syndrome seen in the natives of Indian subcontinent.
      This article gathers the Indian concepts related to semen loss. It also outlines
      belief systems behind problems of Dhat syndrome. 

PMID- 25568482
TI  - A case report of pornography addiction with dhat syndrome.
AB  - A case of pornography addiction with dhat syndrome was diagnosed applying the
      existing criteria for substance dependence in International Classification for
      Diseases-10 and Diagnostic and Statistical Manual of Mental Disorders Fourth
      Edition, Text Revision. There is a lack of clear-cut criteria for identifying and
      defining such behavioural addictions and also lack of medical documents on
      pornography addiction. An applied strategy in lines with any substance addiction
      is used, and we found it helped our patient to gradually deaddict and then
      completely quit watching pornography. This is one of the few cases being reported
      scientifically, and we hope more work will be carried out in this ever increasing
      pornography addiction problem. 

PMID- 25568483
TI  - Females too suffer from Dhat syndrome: A case series and revisit of the concept.
AB  - Dhat syndrome as a clinical entity has been rarely described in females.
      Ethnographic studies suggest that as in males, whitish vaginal discharge in
      females is also associated with depressive and somatic symptoms and many women
      with symptoms of whitish discharge attribute their depressive and somatic
      symptoms to the whitish discharge. In this report, we describe two female
      patients who presented with psychiatric manifestations also with somatic symptoms
      and attributed their somatic complaints to whitish vaginal discharge. In this
      background, we discuss whether this entity requires nosological attention and
      what criteria can be used to define the same. 

PMID- 25568484
TI  - Paroxetine-induced galactorrhea.
AB  - Drug-induced galactorrhea has been reported with agents such as antidopaminergic
      antiemetics, antipsychotics, etc., with few case reports of galactorrhea with
      selective serotonin reuptake inhibitors, including paroxetine, being reported in
      last few decades. Prolactin levels have been found to be either raised or normal
      in these cases. We here report a case of paroxetine induced galactorrhea in a 48
      year-old female patient of obsessive compulsive disorder, having
      hyperprolactinemic and euprolactinemic galactorrhea at different time with a
      pituitary incidentaloma. 

PMID- 25568486
TI  - Late-onset schizophrenia with isolated cavum vergae: Case report and literature
      review.
AB  - Cavum septum pellucidum (CSP) and cavum vergae (CV) have separately and together
      been associated with an increased risk of neurodevelopmental disorders and
      psychosis; however, there is little literature on the psychopathological
      significance of isolated CV, and no previous report of isolated CV in late-onset
      psychosis. We describe an 80-year-old woman who presented with a 1-month history
      of psychotic symptoms qualifying for a diagnosis of schizophreniform disorder.
      Physical (including neurological) examination, bedside cognitive testing, and
      laboratory investigations were all within normal limits. A magnetic resonance
      imaging scan of the brain revealed an insignificant CSP with prominent CV. The
      patient showed almost complete recovery from psychosis after 4-6 weeks of
      treatment with quetiapine (200 mg/day). She maintained improvement with this
      medication at an 18-month follow-up; medication taper was associated with re
      emergence of hallucinations. We briefly discuss CSP and CV in the context of
      vulnerability to psychosis. We examine whether isolated CV is a benign and
      incidental finding versus a biological risk factor for neuropsychiatric illness.
      We suggest specific studies to resolve the uncertainty. 

PMID- 25568487
TI  - A lunatic and a murderer or Berkeley-Hill's machine-gun.

PMID- 25568488
TI  - Appreciation of the study on mentally retarded children and their mothers in
      Madhya Pradesh, India.

PMID- 25568485
TI  - Psychosis in an adolescent with Wilson's disease: A case report and review of the
      literature.
AB  - Neuropsychiatric manifestations are common in Wilson's disease and mainly include
      extrapyramidal and cerebellar symptoms. Presentations with psychotic symptoms
      have been described less frequently. In this report we present the case of a
      young boy with Wilson's disease who developed psychotic symptoms. A 12-year-old
      boy was diagnosed with Wilson's disease on the basis of the physical examination
      findings and low ceruloplasmin levels (8.1 mg/dl). After 2 weeks of being
      diagnosed with Wilson's disease, he developed an acute onset illness,
      characterized by delusion of persecution, fearfulness, hypervigilence and
      decreased sleep. These symptoms were not associated with any confusion, clouding
      of consciousness, hallucinations and affective symptoms. There was no past or
      family history of psychosis. One week after the onset of the symptoms he was
      prescribed tab penicillamine, initially 250 mg/day, which was increased to 500
      mg/day after 3 days. After increase in the dose of penicillamine, his psychiatric
      symptoms worsened and led to hospitalization. A diagnosis of organic delusional
      disorder (F06.2) due to Wilson's disease was considered. Tab risperidone 1 mg/day
      was started, and the dose of penicillamine was reduced with which symptoms
      resolved. Whenever a young adolescent develops psychosis, especially of
      delusional type, the possibility of Wilson's disease must be considered. 

PMID- 25568489
TI  - Association of attention deficit hyperkinetic disorder and epilepsy: Further
      explored.

PMID- 25568490
TI  - Response to article: Behavioral management in children with intellectual
      disabilities in a resource-poor setting in Barwani, India.

PMID- 25568491
TI  - Gilles de la Tourette's syndrome successfully treated with electroconvulsive
      therapy.

PMID- 25568492
TI  - Role of super-specialities in psychiatry.

PMID- 25568493
TI  - Prevalence of depression and anxiety in irritable bowel syndrome: A clinic based
      study from India - Comments on the article.

PMID- 25568494
TI  - Asenapine-induced double incontinence: A rare case report.

PMID- 25568495
TI  - The Rights of Persons with Disabilities Bill, 2014 and persons with mental
      illness.

PMID- 25568496
TI  - How Does Insightful and Emotional Disclosure Bring Potential Health Benefits?:
      Study Based on Online Support Groups for Women with Breast Cancer.
AB  - Despite much research on the beneficial effects of written disclosure, relatively
      little attention has been paid to specifying the mechanism underlying the
      effects. Building upon the two theoretical models (the cognitive adaptation model
      and the emotional exposure-habituation model), this research focused on two
      aspects of disclosure content-insights and emotions-and examined how women with
      breast cancer benefit from written disclosure in online support groups. Using
      survey data collected at baseline and after four months and messages posted in
      bulletin-board-type online groups in between, we analyzed how the content of
      disclosive messages predicted health outcomes. Disclosure of insights led to
      greater improvements in health self-efficacy, emotional well-being, and
      functional well-being, which was mediated by lowered breast cancer concerns.
      Disclosure of negative emotions did not have main effects on health outcomes;
      instead, it weakened the unfavorable association between concerns at baseline and
      functional well-being at follow-up. Our findings support both theoretical models,
      but in regard to different aspects of disclosure content.

PMID- 25568498
TI  - Rhodamine 6G conjugated to gold nanoparticles as labels for both SERS and
      fluorescence?studies on live endothelial cells.
AB  - Fluorescence and surface-enhanced Raman scattering (SERS) spectroscopy were
      employed to investigate the cellular uptake of rhodamine 6G (R6G) alone and of
      R6G loaded with gold nanoparticles (AuNPs) by endothelial cells. R6G plays the
      role of a Raman reporter in SERS but also displays strong fluorescence. The
      presence of bare R6G molecules and R6G-AuNPs in the cytoplasm of the cells is
      detected via the 2D fluorescence of the dye after a 0.5 h of the incubation with
      R6G and R6G-AuNPs, and then the concentration of the dye increases within 4 h of
      exposure. The examination of the cellular uptake of the R6G and R6G-AuNPs species
      at different temperatures suggests that the internalization of the R6G-AuNPs into
      endothelial cells occurs mainly via endocytosis. 3D fluorescence imaging of R6G
      inside cells reveals inhomogeneous distribution of the dye in the cytoplasm. The
      SERS signal of the Raman reporter inside the cell disappears after 2 h of
      incubation with R6G-AuNPs and then amino acid residues, purines and pyrimidines
      become SERS-active via their interactions with the gold. The results highlight
      the significance of using multiple techniques to cover a spectrum of issues in
      the application of SERS nanosensors for probing an intracellular environment
      under comparable and standardized conditions. FigureCellular uptake of bare
      rhodamine 6G and rhodamine 6G adsorbed onto AuNPs were studied on endothelial
      cells using fluorescence and surface-enhanced Raman spectroscopy. The
      internalization of R6G-AuNPs occurs via endocytosis and diffusion resulting in
      uneven distribution in the cytoplasm.

PMID- 25568497
TI  - Nanomaterial-based electrochemical sensing of neurological drugs and
      neurotransmitters.
AB  - Nanomaterial-modified detection systems represent a chief driver towards the
      adoption of electrochemical methods, since nanomaterials enable functional
      tunability, ability to self-assemble, and novel electrical, optical and catalytic
      properties that emerge at this scale. This results in tremendous gains in terms
      of sensitivity, selectivity and versatility. We review the electrochemical
      methods and mechanisms that may be applied to the detection of neurological
      drugs. We focus on understanding how specific nano-sized modifiers may be applied
      to influence the electron transfer event to result in gains in sensitivity,
      selectivity and versatility of the detection system. This critical review is
      structured on the basis of the Anatomical Therapeutic Chemical (ATC)
      Classification System, specifically ATC Code N (neurotransmitters). Specific
      sections are dedicated to the widely used electrodes based on the carbon
      materials, supporting electrolytes, and on electrochemical detection paradigms
      for neurological drugs and neurotransmitters within the groups referred to as ATC
      codes N01 to N07. We finally discuss emerging trends and future challenges such
      as the development of strategies for simultaneous detection of multiple targets
      with high spatial and temporal resolutions, the integration of microfluidic
      strategies for selective and localized analyte pre-concentration, the real-time
      monitoring of neurotransmitter secretions from active cell cultures under electro
      and chemotactic cues, aptamer-based biosensors, and the miniaturization of the
      sensing system for detection in small sample volumes and for enabling cost
      savings due to manufacturing scale-up. The Electronic Supporting Material (ESM)
      includes review articles dealing with the review topic in last 40 years, as well
      as key properties of the analytes, viz., pKa values, half-life of drugs and their
      electrochemical mechanisms. The ESM also defines analytical figures of merit of
      the drugs and neurotransmitters. The article contains 198 references in the main
      manuscript and 207 references in the Electronic Supporting Material. Figure?

PMID- 25568499
TI  - Medical and Psychologic Risks of Maternal Cocaine Use.
AB  - The growing use of crack-cocaine by women of child-bearing age poses significant
      management problems for physicians. Both animal and human studies suggest that
      cocaine exerts significant negative effects on maternal health, the course of
      pregnancy, and infant developmental outcome. Maternal pregnancy complications and
      increased rates of low birth weight and prematurity in infants who are fetally
      exposed are well documented. However, available studies of neurobehavioral
      outcomes for cocaine-exposed infants are still inconclusive. Physicians need to
      become knowledgeable about the potential effects of maternal drug addiction
      during pregnancy to provide appropriate medical care.

PMID- 25568500
TI  - Self-Esteem and the Reproduction of Social Class.
AB  - OBJECTIVE: Although prior research has demonstrated the multiple pathways through
      which socioeconomic attainment occurs, one unexplored avenue regards the role of
      psychological mechanisms such as self-esteem in this process. METHOD: Using three
      waves of data from the National Survey of Families and Households (N = 1,952), we
      employed structural equation models to examine the relationship between parenting
      practices and attitudes, socioeconomic status, offspring's self-esteem, and the
      likelihood of offspring college attendance. RESULTS: Self-esteem was positively
      related to the likelihood of offspring's college attendance. Additionally, self
      esteem was found to be a modest mediator of the relationship between parental
      educational expectations and parental income, respectively, and the likelihood of
      offspring completing or being currently enrolled in college. CONCLUSION: Self
      esteem may constitute one previously unconsidered mechanism for reproducing the
      class structure in the United States.

PMID- 25568501
TI  - Julia-Kocienski Approach to Trifluoromethyl-Substituted Alkenes1.
AB  - A Julia-Kocienski approach to trifluoromethyl-substituted alkenes was evaluated
      in the reactions of 1,3-benzothiazol-2-yl, 1-phenyl-1H-tetrazol-5-yl, and 1
      tbutyl-1H-tetrazol-5-yl 2,2,2-trifluoroethyl sulfones with aldehydes. Among the
      various conditions tested, the best yields were obtained with 1-phenyl-1H
      tetrazol-5-yl 2,2,2-trifluoroethyl sulfone, in CsF-mediated, room temperature
      olefinations in DMSO. Aromatic aldehydes gave (trifluoromethyl)vinyl derivatives
      in 23-86% yields, with generally moderate stereoselectivity. Straightforward
      synthesis of the Julia-Kocienski reagent, and conversion to trifluoromethyl
      substituted alkenes under mild reaction conditions, are the advantages of this
      approach.

PMID- 25568502
TI  - Optimal Tests of Treatment Effects for the Overall Population and Two
      Subpopulations in Randomized Trials, using Sparse Linear Programming.
AB  - We propose new, optimal methods for analyzing randomized trials, when it is
      suspected that treatment effects may differ in two predefined subpopulations.
      Such subpopulations could be defined by a biomarker or risk factor measured at
      baseline. The goal is to simultaneously learn which subpopulations benefit from
      an experimental treatment, while providing strong control of the familywise Type
      I error rate. We formalize this as a multiple testing problem and show it is
      computationally infeasible to solve using existing techniques. Our solution
      involves a novel approach, in which we first transform the original multiple
      testing problem into a large, sparse linear program. We then solve this problem
      using advanced optimization techniques. This general method can solve a variety
      of multiple testing problems and decision theory problems related to optimal
      trial design, for which no solution was previously available. In particular, we
      construct new multiple testing procedures that satisfy minimax and Bayes
      optimality criteria. For a given optimality criterion, our new approach yields
      the optimal tradeoff between power to detect an effect in the overall population
      versus power to detect effects in subpopulations. We demonstrate our approach in
      examples motivated by two randomized trials of new treatments for HIV.

PMID- 25568503
TI  - Decoupling of nutrient and grazer impacts on a benthic estuarine diatom
      assemblage.
AB  - Strong interactions between top-down (consumptive) and bottom-up (resource
      supply) trophic factors occur in many aquatic communities, but these forces can
      act independently in some microphytobenthic communities. Within benthic estuarine
      diatom assemblages, the dynamics of these interactions and how they vary with
      abiotic environmental conditions are not well understood. We conducted a field
      experiment at two sites with varying habitat characteristics to investigate the
      interactive effects of grazers and nutrients on benthic estuarine diatoms. We
      crossed snail (Cerithidea californica) and nutrient (nitrogen and phosphorus)
      addition treatments in enclosures on a restored tidal sandflat and a reference
      tidal mudflat in Mugu Lagoon, southern California. We repeated the study in
      summer 2000 and spring 2001 to assess temporal variation in the interactions.
      Snails caused a large decrease in diatom relative abundance and biomass
      (estimated as surface area); nutrients increased diatom abundance but did not
      alter diatom biomass. Snails and nutrients both reduced average diatom length,
      although the nutrient effect was weaker and temporally variable, occurring in the
      reference mudflat in the spring. There were few interactions between snail and
      nutrient addition treatments, suggesting that links between top-down and bottom
      up forces on the diatom community were weak. There were no consistent differences
      in diatom assemblage characteristics between the two study sites, despite marked
      differences in sediment grain size and other abiotic characteristics between the
      sites. The strong diatom response to herbivores and weaker responses to
      enrichment differed from the previous studies where cyanobacteria increased in
      response to nutrient enrichment, further dissolving the "black box" perception of
      microphytobenthic communities.

PMID- 25568504
TI  - Chromosomal and nuclear alterations in root tip cells of allium cepa L. Induced
      by alprazolam.
AB  - INTRODUCTION: Alprazolam is a triazolobenzodiazepine used in panic disorders and
      other anxiety states. Target organ of Alprazolam is CNS, causing depression of
      respiration and consciousness. AIM: This study aimed to estimate the genotoxic
      potential of Alprazolam using Allium cepa test. METHODS: Allium cepa is one of
      the most suitable plants for detecting different types of xenobiotics. The test
      enables the assessment of different genetic endpoints making possible damage to
      the DNA of humans to be predicted. RESULTS: Alprazolam induced chromosomal
      (anaphase bridges, breaks, lagging and stickiness, abnormal spiralisation,
      multipolarity and polyploidy) and cytological aberrations, especially nuclear
      alterations (nuclear buds, fragmented nucleus and apoptotic bodies, cells without
      nucleus, binucleated and micronucleated cells), morphological alterations in
      shape and size of cells, spindle disturbance and polar deviation in root tip
      meristem cells of Allium cepa at all tested concentrations. Alprazolam also
      caused significant inhibition of mitotic index in these cells. CONCLUSION: These
      changes in cells are indicators of genotoxic potential of Alprazolam suggesting a
      need for further in vitro studies on animal and human lymphocytes as well as in
      vivo studies.

PMID- 25568505
TI  - The frequency of hypertension crises in the emergency medical service department
      in tuzla.
AB  - OBJECTIVES: The aim of this study was to evaluate a frequency and clinical
      presentation of hypertension crises due to age, gender, duration and seriousness
      at Emergency Medical Service Department of the "Dr Mustafa Sehovic" Health Care
      Center Tuzla. METHODS: The research was conducted in the period between November
      2009 and April 2010 and involved 180 examinees of both genders, aging between 30
      and 80 years of age with the diagnosis of arterial hypertension. The examinees
      were divided into two groups: control group consisting of examinees without
      hypertension crisis (95 examinees) and experimental group consisting of examinees
      with hypertensive crisis (85 examinees). Descriptive statistical methods were
      used in the statistical data processing. RESULTS: The research results showed
      that there had been significantly more female examinees than the male ones (60%
      vs. 40%; p=0.007). The average age of male examinees was 55.83+/-11.06 years of
      age, and the average age of female examinees was 59.41+/-11.97 years of age. The
      hypertension crisis frequency was 47.22%, where the hypertensive urgencies were
      statistically significantly more present than the hypertensive emergencies
      (16.47%vs.83.53%; p<0.0001). The largest number of experimental group examinees
      (28.23%) belonged to the age group of 60 to 69 years of age; urgency 26.76% and
      emergency 35.71%. The largest number of examinees with hypertensive crisis
      (49.41%) appeared in the period between 6.00 p.m. and 11.59 p.m. The largest
      number of emergency group examinees (69.01%) had been treated for arterial
      hypertension for ten years, and the examinees from the emergency group (42.86%)
      had been treated for 10, 11 and 20 years. The average blood pressure value at the
      hypertensive crisis examinees was 204.82/126.58 mmHg. CONCLUSIONS: The frequency
      of hypertensive crises in the Emergency Medical Service Department is high and it
      reaches 47.22%. Hypertensive urgencies were significantly more present in terms
      of statistics than the hypertensive emergencies (83.53% vs. 16.47%; p<0.0001).

PMID- 25568506
TI  - Cancer Antigens (CEA and CA 19-9) as Markers of Advanced Stage of Colorectal
      Carcinoma.
AB  - INTRODUCTION: CEA and CA 19-9 are the most common tumor associated antigens used
      in the staging of patients with rectal cancer and other parts of the colon. GOAL:
      of this study was to evaluate the value of CEA and CA 19-9 in serum of patients
      with colon cancer and prove its place in the diagnostic staging. MATERIAL AND
      METHODS: The study was retrospective-prospective performed at the
      Gastroenterohepatology Clinic, Clinical Center of Sarajevo University. The study
      included 91 hospitalized patients who had histologically confirmed diagnosis of
      colon adenocarcinoma in 98% of cases. All patients underwent colonoscopy,
      targeted biopsy and measurement of CEA and CA 19-9 levels in serum. All of them
      underwent abdominal CT and MRI of the pelvis in case of rectal cancer. RESULTS:
      The study analyzed 58 men and 33 women, mean age 66.6 years, with the youngest
      patient at age of 35 and the oldest at age of 89 years. The largest number of
      patients was aged 56-75 years. According to localization 77 patients had
      carcinoma located in the area of the rectum and sigma 37.4 and 37.4 in the
      rectostigmoid area and sigma. Metastases were observed in 37 patients, with
      predominance in the liver (22 cases) and both liver and lungs (5 cases). CEA and
      CA 19-9 were determined in all cases but patients with metastases had high
      values, especially in the two cases of cecoascendent colon cancer where detected
      values were extremely high (1789ng/ml and 10780U/ml). Values of CA19 -9 were
      significantly higher (p<0.05). CEA mean values were highest in patients aged over
      75 years. In case of CA 19-9 high mean values have been recorded in patients aged
      over 75 years with statistically significant differences between the age groups
      (p<0.05). CONCLUSION: CEA and CA19-9 are cancer antigens that are late markers of
      carcinogenesis, with significantly elevated serum concentrations in case of colon
      cancer with already developed metastases. Older age group of patient has
      significantly elevated levels of both antigens. Cancer was twice more common in
      men than in women.

PMID- 25568507
TI  - The prevalence of helicobacter pylori infection in patients with reflux
      esophagitis - our experience.
AB  - INTRODUCTION AND AIM: The role of Helicobacter pylori in esophageal disease has
      not been clearly defined. To clarify this issue, we analyzed 120 patients with
      histologically confirmed esophageal disease. MATERIAL AND METHODS: In this
      prospective study, 120 patients who underwent upper endoscopy examination were
      included; among them 70 patients with clinically, endoscopically and
      histologically confirmed GERD, and 50 patients with BE. This investigation was
      performed in the Clinic of Gastrohepatology in Prishtina, during the period: June
      2009-December 2011. Each patient was investigated for H. pylori infection, by
      performing biopsy for HUT test. RESULTS: In BE group, H. pylori infection was
      present in 16.0% of patients. In GERD group, H. pylori infection was present in
      42.9%, and in patients of the control group, in 52.0% of cases. So, in BE group,
      the prevalence of H. pylori infection showed less significant difference,
      compared to the control group (P = 0.003) and in GERD group (P = 0.0035). Between
      GERD group and the control group there was no significant difference (GERD vs. G
      control. P = 0.421). CONCLUSION: The prevalence of H. pylori infection in
      patients with BE (16%) was lower in comparison with patients with GERD (42.9%)
      and with control group (p <0.01). The prevalence of H. pylori infection in
      patients with BE, especially those with LSBE (9.1%) was very low, which indicates
      a possible protective role of this microorganism.

PMID- 25568508
TI  - The Relationship of Chronic Renal Failure and Body Mass Index in Patients without
      Diabetes.
AB  - INTRODUCTION: Chronic renal failure (CRF) represents a serious medical problem.
      Numerous studies have shown increased body mass index (BMI) as an independent
      risk factor when it comes to the occurrence and development of CRF. MATERIAL AND
      METHODS: The sample in our prospective study presents a total of 150 patients: 30
      for each CRF stage (stages I-IV) and 30 patients in the control group. This study
      did not include patients in the terminal stage of chronic renal failure (stage
      V), as well as patients with newly diagnosed diabetes. Body mass index-BMI was
      calculated using the formula BMI=weight/height(2) (kg/m(2)). In accordance with
      the K/DOQI guidelines patients were divided into four CRF stages. RESULTS: In our
      study there is a predominance of female patients. The mean age of patients was
      55.43 years. Most of the patients had a BMI between 25 and 30 kg/m(2). We did not
      find significant correlation between BMI and the development or CRF. CONCLUSIONS:
      We did not find correlation between increased body mass index (BMI) and the
      occurrence or development of CRF in persons without diabetes.

PMID- 25568509
TI  - Influence of Remifentanil/Propofol Anesthesia on Ventilator-associated Pneumonia
      Occurence After Major Cardiac Surgery.
AB  - The study is designed to evaluate the influence of remifentanil/propofol
      anesthesia on ventilator-associated pneumonia (VAP) occurrence and respiratory
      support (RS) time after major cardiac surgery. MATERIAL AND METHODS: In
      retrospective-prospective study we investigated the respiratory support time and
      VAP occurrence in group of 47 patients with remifentanil/propofol and 35 patients
      with fentanil/midazolam anesthesia after major cardiac surgery in period June
      2009-December 2011. Groups are divided in subgroups depending of who underwent
      cardiac surgery with or without cardiopulmonary by pass (CPB). RESULTS: The time
      of respiratory support (RS) was the shortest in remifentanil group without CPB
      (R/Off 63min +/- 44.3 vs R/On 94min +/- 49.2 p=0,22), but was longer in fentanil
      group (F/Off 142 min +/- 102.2 vs F/On 212 min +/- 102.2 p=0.0014). The duration
      of RS of ON pump remifentanil group was shorter than in ON pump fentanil group
      (R/On 94 min vs F/On 212 min p=0.0011). The time of RS of OFF pump remifentanil
      group was lower than in Off pump entangle group (R/Off 63min +/- 44,3 vs F/Off
      142min +/- 102.2 p=0,021) with statistically significance. Ventilator-associated
      pneumonia was detected in 7 patients (8.5 %). Six patients (17.1%) were from
      entangle group and one patient (2.1%) from remifentanil group. The most common
      isolates were Pseudomonas aeruginosa in all patients and both Pseudomonas
      aeruginosa and Klebsiella pneumonia in one patient. CONCLUSION: The remifentanil
      anesthesia regimen in cardiac surgery decreases length of respiratory support
      duration and can prevent development of VAP. The role of remifentanil anesthesia
      in preventing VAP, as one of the most important risk factor of in-hospital
      mortality after cardiac surgery is still incompletely understood and should be
      investigated further.

PMID- 25568510
TI  - Prevalence and pharmacologic treatment of patients with low back pain treated at
      kosovo energetic corporation.
AB  - INTRODUCTION: Low back pain (LBP) is a common complaint among the general
      population with a subgroup developing chronic and disabling symptoms generating
      large societal costs. Recurrences and functional limitations can be minimized
      with appropriate conservative management, including medications, physical therapy
      modalities, exercise and patient education. OBJECTIVES: The purpose of this study
      was to determine the prevalence of low back complaints in industrial workers, to
      investigate whether individual risk factors involved in the occurrence of LBP,
      and to determine the most frequent used drug in LBP treatment. MATERIALS AND
      METHODS: Data for this study were provided from Kosovo Energetic Corporation. A
      cross-sectional study design was utilized. Self-administered questionnaires were
      distributed among 228 industrial workers. Patient with LBP underwent a
      comprehensive clinical, radiological and biochemical evaluation. RESULTS: showed
      that LBP occurred in 63.5% of workers. Individual factors did not show
      significant associations with LBP. Age (OR=0.99/95% Cl 0.95-1.03), weight
      (OR=1.13/95% Cl 0.99-1.06), height (OR=0.97/95% Cl 0.91-1.02), and work
      experience (OR=1.01/95% Cl 0.97-1.05) increase odds for LBP but not
      significantly. The most frequently used drugs in patients included in this study
      are NSAIDs. In 33 (55.0%) patients for the treatment of LBP two types of drugs
      are administered. CONCLUSION: Increased physical activity, health promotion and
      reduced body weight can prevent morbidity from LBP. A continuous consultation
      with the Clinical Pharmacist demonstrates effective way of dosage and drug re
      evaluation for the patients with LBP.

PMID- 25568511
TI  - Cervical syndrome - the effectiveness of physical therapy interventions.
AB  - INTRODUCTION: The cervical syndrome refers to a set of disorders caused by the
      changes in the cervical spine and the soft-tissue surrounding it, with pain as
      the predominant symptom. Sore neck has been a common problem among a large
      section of today's population. The factors contributing to this issue include the
      modern lifestyle, prolonged sitting and incorrect, fixed or constrained working
      postures. The root of these difficulties is found in the mechanical disorders of
      the cervical spine structures, poor body posture and jerky body movements. In the
      Scandinavian countries neck pain is considered to be a public health problem.
      METHODS: The study evaluated 25 patients with an established diagnosis of
      cervical syndrome. The research was conducted at the PI Institute of Occupational
      and Sports Medicine of Zenica-Doboj Canton. Each patient received twenty physical
      therapy treatment sessions. RESULTS AND CONCLUSIONS: The study included 25
      patients suffering from the cervical syndrome. The statistical analysis of gender
      distribution indicated that 36% of the patients were male, while 64% were female.
      The mean age of study participants was 46.76+/-4,23. The patients ranged in age
      from 39 to 54 years, with no statistically significant difference in the mean age
      of male and female patients, p=0.691. Analysing the types of occupational
      activities performed by the patients, the study found a positive relation between
      neck pain and prolonged sitting at work. The patients who performed office work
      made up 76% of the total number. Each method of physical therapy applied in the
      treatment of neck pain patients proved useful. However, the combination of
      electrotherapy, kinesiotherapy and manual massage proved to be most effective.
      CONCLUSION: The cervical syndrome is a common medical condition primarily
      affecting adult population, with prevalence being higher among women and office
      workers. The condition places a considerable socioeconomic burden on the
      afflicted. Cervical pain ranges greatly in severity - from moderate to
      unbearable, thus leading to high levels of work absence as well as to a decrease
      in the quality of life. Proper physical therapy program can help the patients
      with neck pain return to their normal everyday activities, improve their quality
      of life, as well as reduce the absence from work.

PMID- 25568512
TI  - Impact of complications and bladder cancer stage on quality of life in patients
      with different types of urinary diversions.
AB  - GOAL: Determine correlation between complications and stage of the disease and
      their impact on quality of life in patients with different types of ileal urinary
      derivation after radical cystectomy, and upon estimation of acquired results, to
      suggest the most acceptable type of urinary diversion. PATIENTS AND METHODS: In
      five year period a prospective clinical study was performed on 106 patients, to
      whom a radical cystectomy was performed due to bladder cancer. Patients were
      divided into two groups, 66 patients with ileal conduit derivation and 40
      patients with orthotopic derivation, whereby in each group a comparison between
      reflux and anti-reflux technique of orthotopic bladder was made. All patients
      from both groups filled the Sickness Impact Profile score six months after the
      operation. All patients had CT urography or Intravenous urography performed, as
      well as standard laboratory, vitamin B12 blood values, in order to evaluate early
      (ileus or subileus, wound dehiscence, bladder fistula, rupture of orthotopic
      bladder, urine extravazation) and late complications (VUR, urethral stricture,
      ureter stenosis, metabolic acidosis, mineral dis-balance, hypovitaminosis of
      vitamin B12, increased resorption of bone calcium, urinary infection, kidney
      damage, relapse of primary disease), so as disease stage and it's impact on
      quality of life. RESULTS: From gained results we observe that each category of
      SIP score correlates with different rate of correlation with the type of
      operation, group, T, N, and R grade, except work category. Average value of SIP
      score rises depending on the type of operation and T stage. It is notable that
      there is no difference in T1 stage, no matter the type of operation. So the
      average value of SIP score in T1 stage for conduit was 20.3, for Abol-Enein and
      Ghoneim 17.25 and Hautmann 18.75 respectively. Average value of SIP score in T2
      stage for conduit was 31, for Abol-Enein and Ghoneim 19.1 and Hautmann 17.8.
      Average value of SIP score in T3 stage for conduit was 38.03, for Abol-Enein and
      Ghoneim 18.75 and Hautmann 19.5. SIP score for T4 was present only in patients
      with conduit performed and average value od SIP score was 40.42. There is a high
      level of correlation of late complications and psychosocial and physical
      dimension with their parameters, while for an independent dimension of
      correlation is not significant. Early complications have insignificant
      correlation in all categories of SIP score. CONCLUSION: Upon analyzing quality of
      life and morbidity, significant advantage is given to orthotopic derivations,
      especially Hautmann derivation with Chimney modification, unless there are no
      absolute contraindications for performing this type of operation. Factors which
      mostly influence quality of life are cancer stage, type of derivation, late
      complications and patient age. SIP score, as a well validated questionnaire, are
      applicable in this kind of research.

PMID- 25568513
TI  - Correlation of the body mass index and calcium nephrolithiasis in adult
      population.
AB  - INTRODUCTION: Prevalence of the kidney stones (renal calculi) increase in several
      countries in parallel with the increase of overweight, diabetes (type 2 diabetes)
      and hypertension. GOAL: The goal of our research was to evaluate the connection
      between the calcium nephrolithiasis and overweight, as quantified using the Body
      Mass Index (BMI) of the adult population, with a particular reflection on the age
      groups within it. MATERIAL AND METHODS: The research was prospective and it was
      implemented at the Clinical Center of Banja Luka, at the Urology Clinic in the
      period from 1(st) April 2012 to 1(st) January 2013. The trial encompassed 120
      patients with calcium nephrolithiasis of the upper part of the urinary tract and
      120 patients without nephrolithiasis. A group of patients with the calcium
      nephrolithiasis presented a working group, while a group of patients without
      nephrolithiasis presented a control group. The BMI obtained on the basis of
      bodily weight and height of the patient, where the age and sex of specific
      reference values of the BMI were developed by the Center for Disease Control and
      Prevention (CDC) were not used in the calculation of the BMI. RESULTS: Analyzing
      the values of the BMI in relation to age groups, where there was a statistically
      significant difference in the working group, whereas in the control group there
      was a statistically high significant difference, testing of statistical
      significance of the average value of the BMI was done by observed age groups of
      working and control group, as well as to the total sample of work and control
      group using the Chi-Square test and T-test for independent samples. Having
      observed the age group of 20-40 years, statistically significant differences have
      been noted at the level of risk of 10%, which confirms that there is a connection
      between the categories of the BMI and the group, which the patient comes from
      (Chi-Square test p-0.05), that is, T-test has shown that the values are different
      at the level of 10%, i.e. p<0.1 (p=0.073). Having observed the age group 40-60,
      there was no dependency between the category of the BMI and the group, that is,
      the differences are not statistically significant, p>0.05 (t-test p=0.314). In
      addition to this, the average BMI values are not significantly different, p>0.05
      (t-test p=0.871). Having observed the age group of the older than 60, there was
      no dependency between the category of the BMI and the group, that is, the
      differences are not statistically significant, p>0.05 (Chi-square test p=0.167).
      Having observed the total sample of the working and control group, there was no
      dependency of the category of the BMI and the group (or urolithiasis), p>0.05
      (Chi-Square test p=1.208), whereas the results of the T-test showed that there
      was no statistically significant difference of the arithmetic mean values of the
      BMI working group and control group, p>0.05 (t-test p=0.620). CONCLUSION:
      Overweight in younger age groups of adult population may be connected to the
      occurrence of calcium nephrolithiasis, thus we suggest that urolithiasis should
      be considered with them, as part of overweight, by which a change of living
      habits and the manner of food consumption could prevent this disease.

PMID- 25568515
TI  - Features of postmenopausal uterine haemorrhage.
AB  - INTRODUCTION: Postmenopausal uterine bleeding is a "cancer until proven
      otherwise". Endometrial cancer is a typical disease among postmenopause woman,
      because every bleeding in this age etiology associated with endometrial cancer
      (10-30%). The lifespan of women today has been extended and post menopause today
      last one third of a woman's life. Early diagnosis of endometrial cancer has a
      very high cure rate. Screening for this cancer has limits in practice and is
      necessary given the definition of high-risk groups would be subject to primary
      and secondary prevention. GOAL: Primary to evaluate the leading causes of
      postmenopausal uterine bleeding among patients at risk for endometrial cancer
      (diabetes, obesity, nulliparity, late menopause (after 55 years) and compared
      them with the causes of postmenopausal uterine bleeding patients without this
      risk. MATERIAL AND METHODS: A retrospective, descriptive study with a targeted
      sample of 50 consecutive patients who had registered postmenopausal uterine
      bleeding in high-risk groups (cohorts) and the same number of patients with
      postmenopausal uterine bleeding that does not belong to the risk group (control
      group). Each patient underwent clinical examination, then fractionated
      curettements and its histopathological verification and assessment of treated
      clinical stage of disease with PH analysis of the resected specimens. RESULTS:
      The patients of the studied risk group were significantly affected by endometrial
      cancer compared with the control group (RR=2.45, 95% CI 1.2 4.6, p=0.005).
      Endocervical pathology did not differ between groups. Clinical forms of bleeding:
      for those that are profuse bleeding cancer was present in 54.6% of cases. With
      intermittent bleeding cancer is verified in the 33.3% of patients. Risk patient
      groups with cancer frequently suffer from clinically more advanced stages of
      histologically aggressive endometrial cancer (serous adenocarcinoma-type II, low
      differentiated cancer).

PMID- 25568514
TI  - Clinical characteristics of aerobic vaginitis and its association to vaginal
      candidiasis, trichomonas vaginitis and bacterial vaginosis.
AB  - AIM OF THE WORK: Examine clinical characteristics of aerobic vaginitis and mixed
      infection for the purpose of better diagnostic accuracy and treatment efficiency.
      MATERIALS AND METHODS: Prospective research has been conducted at Clinic for
      Gynecology and Obstetrics, Department for Microbiology and Pathology at
      Polyclinic for laboratory diagnostic and Gynecology and Obstetrics Department at
      Health Center Sapna. Examination included 100 examinees with the signs of
      vaginitis. EXAMINATION CONSISTED OF: anamnesis, clinical, gynecological and
      microbiological examination of vaginal smear. RESULTS: The average age of the
      examinees was 32,62+/-2,6. Examining vaginal smears of the examinees with signs
      of vaginitis in 96% (N-96) different microorganisms have been isolated, while in
      4% (N-4) findings were normal. AV has been found in 51% (N-51) of the examinees,
      Candida albicans in 17% (N-17), BV in 15% (N-15), Trichomonas vaginalis in 13% (N
      13). In 21% (N-21) AV was diagnosed alone while associated with other agents in
      30% (N-30). Most common causes of AV are E. coli (N-55) and E. faecalis (N-52).
      AV and Candida albicanis have been found in (13/30, 43%), Trichomonas vaginalis
      in (9/30, 30%) and BV (8/30, 26%). Vaginal secretion is in 70,05% (N-36) yellow
      coloured, red vagina wall is recorded in 31,13% (N-16) and pruritus in 72,54% (N
      37). Increased pH value of vagina found in 94,10% (N-48). The average pH value of
      vaginal environment was 5,15+/-0,54 and in associated presence of AV and VVC, TV
      and BV was 5,29+/-0,56 which is higher value considering presence of AV alone but
      that is not statistically significant difference (p>0,05). Amino-odor test was
      positive in 29,94% (N-15) of associated infections. Lactobacilli are absent,
      while leukocytes are increased in 100% (N-51) of the examinees with AV.
      CONCLUSION: AV is vaginal infection similar to other vaginal infections. It is
      important to be careful while diagnosing because the treatment of AV
      differentiates from treatment of other vaginitis.

PMID- 25568516
TI  - Frequency of vaginal birth after cesarean section at clinic of gynecology and
      obstetrics in sarajevo.
AB  - At the Clinic of Gynecology and Obstetrics, Clinical Center University of
      Sarajevo there is a trend of increasing number of cesarean deliveries in the last
      15 years. MATERIAL AND METHODS: During the 2012 percentage of Caesarean sections
      was 35 %, which represents a true pandemic in obstetrics profession and all
      scientific postulates are threatened by these practices. Of the total number of
      vaginal births only 48 deliveries were after previous cesarean section. Of the
      total number of subjects in which the delivery is completed vaginally after a
      previous cesarean delivery in 5 (10.42 %) was used vacuum extraction, forceps was
      not used, while manual exploration of the uterus in order to check the condition
      of the scar of a previous cesarean section was performed in 32 (66.67%) cases.
      RESULTS AND DISCUSSION: The largest number of respondents who were surveyed were
      at age from 31 - 35 years (n=25), followed by group between 26-30 years (39.58%).
      The analysis of complications of vaginal birth after Caesarean delivery revealed
      that 93.75 % of the patients did not have any complications, at 4.17 % occured
      postpartum hemorrhage and in one patient febrile condition. Birth after cesarean
      delivery can be successfully completed vaginally, with a careful application of
      prostaglandins, with a good estimate of an experienced obstetrician, and adequate
      conditions to complete delivery by caesarean section if a vaginal birth is not
      going in the right direction and as planned.

PMID- 25568518
TI  - Pneumonia as the most common lower respiratory tract infection.
AB  - INTRODUCTION: Pneumonia is the most serious inflammatory disease of the
      respiratory system and also the most common infectious disease. Even now, in the
      21(st) century, pneumonia occupies a prominent place in clinical medicine and
      public health. We are confronted daily with the increased number of patients, as
      well as the constant increase in annual mortality due to this infectious disease.
      GOAL: The goal was to investigate the prevalence and pneumonia characteristics as
      the most serious lower respiratory tract infection, the incidence of typical and
      atypical pneumonia, hospitalization duration of the patients at the Clinic of
      Infectious Diseases, Clinical Center of Sarajevo University CCUS. PATIENTS AND
      METHODS: From January 2011 until December 2012 the study involved 100
      hospitalized patients with infections of the lower respiratory tract at the
      Clinic of Infectious Diseases CCUS. RESULTS: Among the most common infections the
      pneumonia is highly represented. Lung X-Ray in two planes, by all protocols,
      demonstrated with the auscultatory finding has the highest value in the diagnosis
      of clinical pneumonieae. A statistically significant difference among our
      hospitalized patients, compared to typical and atypical pneumonia, is in favor of
      the first-typical bacterial pneumonia. Hospitalization duration ranges between 7
      14 days. CONCLUSION: We believe that the introduction of the pneumococcal vaccine
      (PCV) should reduce the number of pneumonia caused by this bacterium.
      Recommendations for its use also come from the WHO. Until December 2012, WHO
      added 86 states in the PCV immunization as a part of their national immunization
      programs. Pneumococcal conjugate vaccine (PCV) is safe and effective for the
      reduction in number of patients suffering from pneumonia caused by St.
      pneumoniae. In particular, the vaccine is a significant protection for children,
      who due to age and severity of the disease must remain under medical supervision.
      In elderly vaccine is important and useful as preventive measure, due to their
      biological characteristics and life circumstances which mark this group as
      vulnerable population, like the youngest, and can be fatal for them.

PMID- 25568519
TI  - Endoprosthesis and obesity.
AB  - INTRODUCTION: Obesity represents a significant risk factor in the pathophysiology
      of degenerative changes in coxarthrosis. OBJECTIVE: The study aims to investigate
      obesity as a risk factor in the examined sample comprising 136 patients who
      underwent hip endoprothesis implantation. MATERIAL AND METHODS: The series
      comprised 136 patients with a hip endoprosthesis implanted, where the patients'
      BMI, amount of blood used, duration of surgery, number of assistants, and type of
      anaesthesia were observed. Wounds and late post-operative complications,
      infections, haemorrhage, vein thrombosis, endoprosthesis dislocations, length of
      inpatient stay, start of physical therapy and full weight-bearing were also
      observed. The observation period lasted six months on average. DISCUSSION: In
      simple terms, the three greatest factors when implanting a hip endoprosthesis are
      as follows: properties of the endoprosthesis, the orthopaedic surgeon's skill and
      experience, and individual characteristics of the patient, i.e. age, sex, health
      condition, body weight, BMI, adequate physical therapy. CONCLUSION: We believe
      that the implantation of a hip endoprosthesis should be postponed for patients
      with a BMI exceeding 29.99. Such patients should receive endocrine treatment,
      they should undergo a weight loss programme in order to reduce their body weight
      and in order to reduce their BMI to under 29.99.

PMID- 25568517
TI  - Air pollution in pristina, influence on cardiovascular hospital morbidity.
AB  - INTRODUCTION: Numerous studies observed health effects of particulate air
      pollution. Ambient air quality is particularly bad in Pristina. The principal
      sources of contaminants are sulfur dioxide (SO2), nitrogen oxides NO and NO2
      (NOx), ozone (O3), lead (Pb), carbon dioxide (CO2), particulate matter (PM or
      dust). OBJECTIVE: to investigate effects of concentrations of pollutants in
      ambient air on hospital admissions for cardiovascular disease in UCCK- Pristina.
      METHODS: Retrospective ecological study. During the three year analytical
      research predict the potential benefit of decreasing for concentration of PM 2.5,
      PM 10 were measured in two station in Pristina. The study population consisted of
      all hospitalization patient in intern clinic for 2010,2011 and 2012 year. Air
      pollution measurements will be used by KHMI data for the year of 2010, 2011 and
      2012 for the municipality of. PRISTINA IN THE MEASUREMENTS POINT IN: KHMI-MESP
      which is equipped with automatic analyzer- Air Compact Monitoring System (Version
      2.2) recordum MESSTECHNIK GmbH. Statistical data processing will be done with
      SPSS 17.0 statistical package. RESULTS: Based on the results obtained during the
      study period concentrated PM are higher level than standards value. The results
      showed that the number of hospital admissions for cardiovascular disease are
      positively correlated with concentration pollutants. Results show clear seasonal
      variation in the effects of PM on hospital admissions in Kosovo. The study period
      was short but the mean daily admissions for cardiovascular illnesses were quite
      large. CONCLUSION: The main source for air pollution was coal-burned power plant
      and traffic (old vehicles) in Kosovo.

PMID- 25568520
TI  - Single stage turn in perforator infraorbital artery island flap for nasal ala
      reconstruction.
AB  - BACKGROUND: The reconstruction of fullthickness nasal alla defects is challenging
      procedure. Use of local flaps is acceptable approach. Flap based on infraorbital
      artery could be used for primary reconstruction of nasal ala defects. METHODS:
      The prospective study include consecutive series of 15 patients with advanced
      skin carcinoma of the nasal ala and medial cheek staged T4 by TNM, in whom the
      turn in infraorbital flap was used. The patient characteristics, type of
      carcinoma and complications were analyzed. RESULTS: The turn in infraorbital flap
      was used mostly in male patients (80%), mean age 64 years. The basal cell skin
      carcinoma was found in 60%. Skin layer was skin grafted. All flaps survived, but
      in one case a partial wound dehiscence in one partial skin graft loss was found,
      and in two patients partial nasal obstruction occurred. These three complications
      were solved as secondary procedures under local anesthesia. CONCLUSION: Full
      thickness defect of the nasal ala can be properly reconstructed using flap based
      on infraorbital artery providing exceptional esthetic and functional results, as
      single stage procedure.

PMID- 25568521
TI  - Are we on the path to solve the enigma of resistant hypertension: renal
      sympathetic denervation.
AB  - Renal sympathetic denervation (RSD) opens new perspectives and possibilities not
      only in the treatment of resistant hypertension but also of other cardiometabolic
      diseases. In patients with hypertension, it has been demonstrated that activity
      of the sympathetic nervous system correlates with grade of hypertension.
      Decreasing sympathetic activity using RSD significantly reduces blood pressure in
      resistant hypertension. It is too early to say a definite opinion about
      appropriateness of this method in the treatment of resistant hypertension,
      because there are not great studies with huge number of the patients. After we
      get and evaluate these results through a longer span of time, only than we shall
      know what is the role of RSD in the treatment of resistant hypertension and other
      cardiometabolic conditions related to increased function of the sympathetic
      nervous system, such as heart failure, diabetes mellitus, obstructive sleep
      apnea, renal disease with microalbuminuria and macroalbuminuria. 

PMID- 25568522
TI  - New Views on Cesarean Section, its Possible Complications and Long-Term
      Consequences for Children's Health.
AB  - Historical developments and advancements in cesarean section techniques and
      logistics have reduced the maternal and neonatal risks associated with the
      procedure, while increasing the number of operatively completed pregnancies for
      medically unjustifiable reasons. The uncritical attitude towards cesarean section
      and the fast emergence of 'modern' diseases such as obesity at a young age,
      asthma, type 1 diabetes mellitus and various forms of dermatitis have stimulated
      researches associating cesarean section with these diseases. Intestinal flora of
      the children born by cesarean section contains less bifidobacteria, i.e. their
      intestinal flora is similar to the intestinal flora in diabetic individuals. In
      children born by cesarean section, the 'good' maternal bacterial that are
      normally found in the maternal birth canal and rectum are lacking, while the
      'bad' bacteria that may endanger the child's immune system are frequently
      present. In children born by vaginal delivery, the 'good' maternal bacteria
      stimulate the newborn's white blood cells and other components of the immune
      system, which has been taken as a basis for the hypotheses explaining the evident
      association of the above morbidities and delivery by cesarean section. 

PMID- 25568523
TI  - Atmospheric pressure changes are associated with type a acute aortic dissections
      and spontaneous abdominal aortic aneurysm rupture in tuzla canton.
AB  - AIM: The aim of this study was to investigate a relationship between seasonal
      variation and incidence of type A acute aortic dissection (AAD) and spontaneous
      abdominal aneurysm rupture (rAAA) in Canton Tuzla, Bosnia and Herzegovina.
      PATIENTS AND METHODS: A total of 81 cases, 41 AAD and 40 of ruptured AAA were
      identified from one center over a 6-year, from 2008 till 2013. In 2012 were
      admitted (45.6% or 36 patients). RESULTS: Seasonal analysis showed that 19(23.4%)
      patients were admitted in spring, 15(18.5) in summer, 26(32%) in autumn and
      21(25.9) in winter. The most frequent period was autumn/winter with 47 or 58%
      patients. A causal link between atmospheric pressure (AP) and incidence of rAAA
      and AAD on seasonal and monthly basis was found.

PMID- 25568524
TI  - Estimated Glomerular Filtration Rate (eGFR) Values as Predictor of Renal
      Insufficiency in Advanced Stages of Liver Diseases with Different Etiology.
AB  - BACKGROUND: Various complications occur in patients with advanced stages of liver
      diseases. Renal dysfunction, a parameter included in the MELD score, is the most
      important prognostic factor. There is a strong need in clinical practice to
      estimate the GFR in this patients. OBJECTIVES: The aim of our study was to detect
      differences in renal function among patients with different stages of chronic
      liver diseases caused by HBV and HCV, also to determine the impact of viral
      etiology and gender on the values of eGFR and renal function. PATIENTS AND
      METHODS: This was an observational cross-sectional study performed on patients
      with HBV and HCV chronic hepatitis, cirrhosis and HCC caused by these viruses
      hospitalized during period 2009-2014 in the Clinic of Gastroenterohepatology,
      Clinical Center University of Sarajevo. The estimated GFR (eGFR) was evaluated by
      the MDRD4 method. For the processing of data SPSS 21.0 statistical software was
      used. Statistical methods used in this study where: analysis of variance test
      (ANOVA test), Student's t-test for independent samples and Pearson coefficient of
      correlation. The level of significance was p <0.05. RESULTS: Among this three
      groups of patients there was a statistically significant difference in eGFR (F=
      18.79, p<0.05), i.e. increase of degree of liver damage was related with increase
      of renal impairment, as reflected by a significant reduction in estimated
      glomerular filtration rate. Gender had no significant effect on eGFR and renal
      function (p>0.05), except in group of patients with HCC (p<0.05). Etiology had no
      significant effect on eGFR and renal (p>0.05). There was statistically
      significant inverse correlation between glomerular filtration rate and liver
      enzymes AST (-.184) and GGT (-.181). CONCLUSIONS: By calculation of GFR, we
      determined the existence of a significant reduction of kidney function through
      progression of liver damage from HBV and HCV chronic hepatitis, liver cirrhosis
      to HCC caused by these viruses, which drawing attention to the importance of the
      assessment of renal function in patients with this liver pathologies. Gender and
      etiology had no significant effect on eGFR and impairment of renal function.
      Given the statistically significant inverse correlation between eGFR and AST and
      GGT this liver enzymes may have important role as marker for both renal and
      hepatic injury.

PMID- 25568525
TI  - Poorly Regulated Blood Glucose in Diabetic Patients-predictor of Acute
      Infections.
AB  - INTRODUCTION: Diabetes mellitus, the most frequent endocrinology disease is a
      predisposing factor for infections. Diabetic patients have 4,4 times greater risk
      of systemic infection than non diabetics. AIM: a) To determine the prevalence and
      characteristics of acute infectious diseases in hospitalized diabetics; b) To
      correlate values of blood glucose levels and HbA1c with acute infections in
      hospitalized diabetics; c) To identify the etiology of infectious diseases.
      MATERIAL AND METHODS: The study included 450 diabetic patients hospitalized in
      the 24-month period in the Intensive care unit of the Clinic for Endocrinology,
      Diabetes and Metabolic Disorders CCUS. In 204 patients (45,3%) there was an acute
      infectious condition and the following data was registered: a) gender and age; b)
      basic illness; c) laboratory parameters of inflammation (Le, CRP); d) blood
      glucose upon admission, parameters of glucoregulation (HbA1c, fructosamine); e)
      type of infection; f) verification of etiological agent; g) late complications of
      diabetes; and h) outcome. RESULTS: Out of 204 diabetic patients with infection,
      there was 35,3% men and 64,7% women. More than half of patients (61%) were in the
      age group 61-80 years. The most common primary disease was Diabetes mellitus type
      2. HbA1c and fructosamine were significantly increased in diabetic patients with
      acute infection compared to diabetics without acute infection. There is a
      positive correlation between HbA1c levels and CRP, and blood glucose and CRP in
      diabetic patients with acute infection. Most frequent infections: urinary tract
      infection (70,0%), followed by respiratory infections (11,8%), soft tissue
      infections (10,3%), generalized-bacteremia / sepsis (6,9%). The most common cause
      of urinary infection and generalized infection was Escherichia colli. The most
      common bacteria causing soft tissue infections was Staphylococcus aureus.
      CONCLUSION: Almost half (45,3%) of hospitalized diabetic patients had acute
      infectious condition. They present most frequently in women, aged 61-80 years,
      with Type 2 Diabetes mellitus. HbA1c and fructosamine were significantly
      increased in diabetic patients with acute infection. There is a positive
      correlation between the parameters of inflammation and glucoregulation in
      diabetics with acute infection. Most frequent was a urinary tract infection and
      the most common causative agent was Escherichia coli. The most common cause of
      soft tissue infections was Staphylococcus aureus. Out of 21 patients with
      verified soft tissue infections, 18 of them (85,7%) had confirmed diagnosis of
      diabetic microangiopathy diabetica. A total of 96,1% of patients fully recovered.

PMID- 25568526
TI  - The toxic effect on leukocyte lineage of antimicrobial therapy in urinary and
      respiratory infections.
AB  - INTRODUCTION: Antimicrobials are widely used in infectious diseases. Only the
      timely intervention will contribute to the positive outcome of the disease.
      Unjustified use of antimicrobial prophylaxis may have adverse effects, i.e.,
      result in bacterial resistance to existing antimicrobials, as well as toxic
      effects on leukocyte lineage and other parameters of the blood. GOAL: The goal of
      this study was to confirm that the antimicrobial therapy of urinary,
      gynecological and respiratory infections has a toxic effect on leukocyte lineage.
      Followed by lowered immunity and the emergence of risk for health complications
      especially in oncology and other immunodeficient patients for whom to apply
      pharmacotherapy it is necessary to have adequate immunity, or white blood cell
      count that is greater than 4.0x10(9)/L. MATERIAL AND METHODS: A prospective
      retrospective study was conducted on a sample of 30 patients in a Primary Health
      Care Center in Gracanica during the period from March 01, 2013 until April 01,
      2014. Testing of this sample was conducted by survey on health status and
      treatment, or on taking of antimicrobial therapy and other treatment regimens,
      with the referral diagnosis and determination of leukocytes count in by
      hematology counter SYSMEX. Results of leukocytes below and close to the lower
      reference values were statistically analyzed by Students t-test. RESULTS: Mean
      WBC count in the group treated with antimicrobial therapy was 3.687+/-0.83
      x10(9)/L, in the group which during repeated infection did not use the
      antimicrobial therapy 5.09+/-1.04 x10(9)/L, and in the control group of healthy
      subjects 7.178+/-1.038 x10(9)/L. Statistical analysis with Student's t test
      indicate highly significant differences between group of patients that used
      antimicrobial therapy with the group of patient that did not used antimicrobial
      during repeated infection (t=6.091; p=0.0001), as well as significant differences
      in mean WBC count of both of these groups and the controls (t=4.984; p=0.0001,
      and t=8.402, p=0.0001). CONCLUSION: Use of antimicrobial drugs leads to serious
      toxic reactions, or leukopenia. Indications for the use of antimicrobial therapy
      must be strictly followed, because banal, frequent infections are not indication
      for antimicrobial therapy. It is necessary to know the types of infection causes.
      Important is the proper and timely selection of antimicrobial therapy. When
      selecting the drug we should bear in mind its antimicrobial activity,
      pharmacokinetic and toxic properties, as well as patient health status. Possible
      is also the application of preventive medicine as well as other manner of solving
      infection.

PMID- 25568527
TI  - Proximal femoral nail antirotation in treatment of fractures of proximal femur.
AB  - INTRODUCTION: Fractures of the proximal femur and hip are relatively common
      injuries in adults and common source of morbidity and mortality among the
      elderly. Many methods have been recommended for the treatment of
      intertrochanteric fractures. MATERIAL AND METHODS: We retrospective analyzed all
      the patients with fractures of the hip treated with proximal femoral nail
      antirotation (PFNA) at the Clinic of Orthopedic and Traumatology, University
      Clinical Centre Tuzla from the first of January 2012 to 31 December 2012 years.
      The study included 63 patients averaged 73.6+/-11.9 years (range, 29 to 88
      years). Fracture type was classified as intertrochanteric (Arbeitsgemeinschaft
      fur Osteosynthesefragen classification 31.A.1, A.2 and A.3) and subtrochanteric
      fractures (Seinsheimer classification). RESULTS AND DISCUSSION: The ratio between
      the genders female-male was 1.6:1. There was statistically significant difference
      prevalence of female compared to male patients (p=0.012). There were 31 left and
      32 right hip fractured. Low energy trauma was the cause of fractures in 57(90.5%)
      patients. Averaged waiting time for hospitalization was 3.2+/-7.5 days (range, 0
      to 32 days). 44 patients were admitted the same day upon injuring. The average
      waiting time for the treatment was 3.6+/-5.7 days. The ratio between with or
      without co-existent disease was 4.7:1. During the three months postoperatively
      with ASA score 3 and 4 six patients died. There were no significant differences
      in deaths from ASA score 1 and 2 (p=0.52). Reoperation for the treatment of
      implant or fracture-related complications was required in three (4.7%) patients
      (infection, reimplantation and extraction). Three patient developed deep vein
      thrombosis. Statistically significant difference was found in the deaths in the
      first three months compared to the next three months (p=0.02). We found
      statistically significant difference between pre-injury and postoperative
      mobility score (p=0.0001). CONCLUSION: PFNA is an excellent device for
      osteosynthesis as it can be easily inserted. Moreover, it provides stable
      fixation, which allows early full weightbearing mobilization of the patient.

PMID- 25568528
TI  - Epidemiological characteristics and functional disability of multiple sclerosis
      patients in kosovo.
AB  - BACKGROUND AND OBJECTIVES: Multiple Sclerosis (MS) is a chronic recurrent
      neurological disease that affects the Central Nervous System. This study aims to
      determine epidemiological factors that affect the appearance of MS, such as:
      incidence, prevalence, mortality, case appearance in accordance with the disease
      phase RRMS, SPMS, PPMS, gender, age, age group, and EDSS. MATERIALS AND METHODS:
      Deals with analyzing diagnosed and treated patients in the Clinic of Neurology in
      Prishtina during the period of 2003-2012. The research was conducted through a
      questionnaire applied in the diagnosed cases of MS. Information on patients was
      gathered from: history of illness, discharge reports and other relevant documents
      on MS illness. Clinical and epidemiological-descriptive study methods were used.
      The acquired results are shown through tables, graphics. Statistical processing
      was conducted with Microsoft Office Excel. RESULTS: From the total number of
      doubtful hospitalized cases of demyelinization (644) in the Clinic of Neurology
      in Prishtina, 412 cases (64%) were diagnosed with MS. For the period of 2003-2012
      the prevalence of MS has been 19.6 of patients in 100,000 inhabitants. MS
      incidence rate was 0.95 of patients in 100,000 inhabitants. MS mortality rate was
      0.14 of deceased in 100,000 inhabitants. The ratio female - male is 2.3:1. A
      larger number of patients fall within the age group of 30-39 years-old. Clinical
      form trends: RRSM 72.3%, SPSM 22.6%, PPSM 5.1%. The rate of EDSS 78.3% (0-3.5),
      14.9% (4-6.5), 6.8% (7-9).

PMID- 25568529
TI  - Operative treatment of the knee contractures in cerebral palsy patients.
AB  - INTRODUCTION: Knee flexion is one of the main problems of the lower extremities
      in cerebral palsy patients. Many operative procedures are recommended for
      contractures of the knee in cerebral palsy patients. We performed simple
      operation and analyzed the results after operative treatment with nine years
      follow up. METHOD: 85 patients with spastic cerebral palsy were treated in period
      2001 - 2010. 40 were ambulatory and 45 non ambulatory with ability to stand with
      support. All of them underwent same surgical procedure with distal hamstrings
      lengthening. Tenotomies were performed on m. semitendinosus, m. semimembranosus,
      m. gracillis and biceps femoris. Only m. semitendinosus was tenotomized
      completely, other muscles were tenotomized only on tendinous part. The patients
      had a plaster immobilization for five days after the surgery with the knee
      extended. RESULTS: All 85 patients had improvement of the popliteal angle pre and
      post operative respectively. Improvement in the crouch gait was noticed in the
      period of rehabilitation. We had no complication with the wound. Three of the
      patients had overcorrection and achieved recurvatum of the knees. CONCLUSION: We
      consider this procedure very simple with satisfying improvement of standing,
      walking and sitting abilities in children with spastic cerebral palsy.

PMID- 25568530
TI  - Influence of maternal anemia during pregnancy on placenta and newborns.
AB  - INTRODUCTION: Sideropenic anemia is a common pregnancy disorder. Depending on
      severity, maternal anemia can significantly influence morphometric characteristic
      of placental tissue, pregnancy course and outcome. OBJECTIVES: to estimate if
      maternal anemia a) results with significant placental changes; b) influence on
      newborn weight, length and vitality. PATIENTS MATERIAL AND METHODS: Research
      included 100 women and their newborns, 50 anemic, and 50 women in the control
      group. Sixty placentas were collected, placental mass and volume was determined,
      and blood vessels of terminal villi were stereologically analyzed. Newborns mass
      and body length, and Apgar scores within 1 and 5 minutes after delivery were
      recorded. THE RESULTS: Placentas of anemic pregnant women showed significant
      increase of terminal villi blood vessels (224,18 vs. 197,00 cm(3); p<0,0001), but
      total placental mass and volume did not differ significantly. Anemic mothers'
      newborns were significantly shorter (51,76 vs. 55,54 cm; p<0,0001), smaller body
      mass (3048,00 vs. 3615,60 g; p<0,0001) and delivered one week early (38,2 vs.
      39,2 GW; p<0,0001), but not significantly poorer vitality (p>0,05) comparing with
      the control group. CONCLUSION: Sideropenic anemia increase placental maturity,
      that could be a possible cause of earlier spontaneous delivery among anemic
      women. The anemic mothers' newborns are shorter and lower body mass, but not
      poorer vitality index.

PMID- 25568531
TI  - Prison health in transitional Albania.
AB  - AIM: The information about prisoners' health in transitional countries including
      Albania is limited. The aim of our study was to assess the health status and its
      correlates among adult prisoners in Albania, a post-communist country in
      Southeast Europe. METHODS: This was a cross-sectional study conducted in 2013
      including 401 prisoners in Albania [290 (72%) males and 111 (28%) females]. All
      participants were administered an anonymous and structured questionnaire
      including information on self-perceived health status, health-related problems,
      lifestyle factors (smoking, alcohol intake and drug use) and demographic and
      socioeconomic characteristics (age, sex, educational attainment and income
      level). Binary logistic regression was used to assess the association between
      self-reported health status and covariates. RESULTS: Overall, 173 (43.1%) of
      prisoners included in this study reported a poor health status, with a clear
      predominance of the female gender (P<0.01). Overall, 28.1% of prisoners reported
      the presence of at least one disease. The overall prevalence of smoking,
      excessive alcohol consumption and drug use were 59.1%, 34.9% and 10.2%,
      respectively. Upon multivariable-adjustment, poor self-perceived health status
      was positively associated with female gender (OR=2.01, 95%CI=1.41-2.96), smoking
      (OR=1.58, 95%CI=1.29-2.04), excessive alcohol consumption (OR=1.71, 95%CI=1.38
      2.13) and the presence of diseases (OR=1.86, 95%CI=1.52-2.87). CONCLUSION: This
      study provides important information about the health status among Albanian
      prisoners. There is an urgent need for Albania to make a significant progress in
      health services provision for prisoners, which constitute a particularly
      vulnerable population subgroup.

PMID- 25568532
TI  - Analysis of body mass components in national club football players in republic of
      macedonia.
AB  - AIM: This study aims to analyze body composition in adult male football players
      and its changes during adulthood. METHODS: Adult male football players (n=942,
      mean age 24.11 +/-4.69y), all members of national competitive clubs from
      Macedonia were included in the study. The absolute and the relative body
      components were calculated: lean body mass (LBMkg), muscle mass (MMkg; MM%), bone
      mass (BMkg; BM%) and fat components (FMkg; FM%), using the anthropometric
      protocol by Matiegka. RESULTS: Mean values of anthropometric measures for all
      included participants were as follows: height=178.39+/-6.11cm; weight=77.02+/
      7.57; LBM=65.65+/-6.38; MM%=53.23+/-2.78; BM%=17.05+/-1.27; FM%=14.58+/-1.48.
      Descriptive statistics for these parameters was made for age specific groups.
      CONCLUSIONS: The results obtained could be used as reference values for adult
      football players in Republic of Macedonia. In the examined age span (18-35 years)
      a slight increase of absolute values of all three body components has been
      registered with advancing age. The most significant increase in the absolute
      values was registered for the muscle component, followed by the fat and bone
      components, respectively. Regarding the relative values (%), the muscle and the
      fat components showed an equally slight positive correlation with the age
      increase of 1 year, whilst the bone component decreased with advancing age.

PMID- 25568533
TI  - Clinical Effects of Portulaca Oleracea Seeds on Dyslipidemia in Obese
      Adolescents: a Triple-blinded Randomized Controlled Trial.
AB  - OBJECTIVE: Childhood obesity is a major public health concern worldwide while the
      current epidemic may be secondary to over consumption of high-fat, energy-rich
      foods. Purslane (Portulaca oleracea L.) has been traditionally used in medicine
      for several antioxidant and anti-atherogenic activities. In this study the anti
      dyslipidemic effects of P.oleracea was evaluated in obese adolescents. METHODS:
      In this triple-blinded randomized placebo-controlled clinical trial which was
      done from July 2011 to June 2012, obese adolescent patients whom were referred to
      the Isfahan Cardiovascular Research Institute (Iran) were randomly allocated to
      the two arms of cases and controls. The cases group was asked to take one capsule
      containing powdered P. oleracea seeds (500 milligrams) two times a day for one
      month, and the controls group were asked to take identical but placebo (lactose)
      capsules in the same way. Biochemical parameters including 12-hours fasting serum
      levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured
      before the initiation and after the completion of the study protocol. FINDINGS:
      Total cholesterol, LDL-C, and TG showed statistically significant changes over
      time (one month) in the P. oleracea group (p < 0.05). However, between-group
      analysis using general linear model (multivariate) test revealed that the
      differences in the mentioned parameters between two study groups were
      statistically significant just for LDL-C and TG, while others did not differ
      significantly. CONCLUSION: P. oleracea L. may have positive effects on serum
      lipids profile which may be attributed to its polyphenolic and antioxidant
      compounds. This herbal drug seems to be well-tolerated in adolescent population
      as well. Further studies are recommended.

PMID- 25568534
TI  - Epidemiological characteristics of meningococcal meningitis in the area of zenica
      doboj canton in period from 2008 to 2012.
AB  - INTRODUCTION: Meningococcal meningitis now represents a significant public health
      problem, not only in developing countries but also in developed ones. The disease
      usually occurs sporadically, and much less in smaller epidemics. MATERIAL AND
      METHODS: We retrospectively analyzed the epidemiological characteristics of
      meningococcal meningitis in the area of Zenica-Doboj Canton in the five-year
      period from 2008 to 2012th. In total there were 38 reported and hospitalized
      patients, with an average of 7-8 patients per year. RESULTS: Most commonly
      disease occurred in infants and young children (28.9%). The highest number was
      recorded in 2011, 10 cases or (26.3%). Most patients in the monitored period were
      registered in the municipality of Zenica-12 cases (31.6%) and Zepce 8 cases
      (21.1%). All hospitalized patients were sporadic cases, there has never been an
      epidemic in the observed period. CONCLUSIONS: Epidemic Meningitis is a very
      serious disease and a significant public health problem that requires a serious
      medical scientific approach for its resolution, primarily in finding adequate
      vaccine and its administration.

PMID- 25568535
TI  - Therapeutic Modalities of Exudative Age-related Macular Degeneration.
AB  - INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of
      irreversible serious vision damage in persons over 50 years of age. In treating
      AMD many medicaments are applied such as inhibitors of vascular endothelial
      growth factor (VEGF), have been very carefully included over the last few years
      after a series of study research. AIMS: To analyze the past methods of treatment,
      discuss emerging therapies which could advance the treatment of exudative AMD.
      The past anti-VEGF therapies require frequent repetitions of administration, with
      uncertain visual acuity recovery, as not all patients react to anti-VEGF therapy.
      Consequently, there is a need to find out additional therapies which could
      improve the treatment of exudative AMD. The real aim in the treating of AMD is to
      prevent CNV development. METHODS: A survey of the current clinical research and
      results in the field of the present and future treatments of exudative AMD.
      RESULTS: There are many areas of research into new methods of the exudative AMD
      treatment. CONCLUSION: The future therapies for exudative AMD treatment have a
      potential not only to reduce the frequency of administration and follow-up
      visits, but also to improve effects of treatment by targeting additional ways of
      CNV development, increasing the aptitude of target binding and extending
      durability of treatment.

PMID- 25568536
TI  - Giant ethmoid osteoma originated from the lamina papyracea.
AB  - INTRODUCTION: Osteomas are slow- growing, benign tumors. They are the most common
      neoplasms of the paranasal sinuses. They are usually originates from the frontal
      and ethmoid sinus and much less frequently seen in the maxillary and sphenoid
      sinuses. Although the lamina papyracea is a part of ethmoid bone, a giant osteoma
      originated from the lamina papyracea is very uncommon. An osteoma of the
      paranasal sinus is usually asymptomatic. Headache, proptosis, epiphora, diplopia,
      dizziness, facial deformity, face pain and cerebral complications are possible
      symptoms. The treatment of the paranasal osteomas are controversial. CASE REPORT:
      A 65 year old patient that applied with stuffiness and headache to our clinic.
      She has had a smooth mass in the right nasal cavity. Paranasal sinus tomography
      showed an osseous lesion, the size of 4x 3 cm, arising from the right lamina
      papyracea. The mass excised endoscopically and reported as osteoma
      histopathologically. There was no complication. After 9 months, there was no
      recurrence. CONCLUSION: Giant osteomas of paranasal sinuses, especially
      originated from the lamina papyracea are rare. They can be treated successfully
      by endoscopic approaches without any recurrence and complication despite its
      size.

PMID- 25568537
TI  - Treatment of congenital aniridia associated with subluxated infantile cataract.
AB  - A 5 year old boy was presented at Eye clinic University clinical center Tuzla
      with congenital aniridia in both eyes. Clinical examination revealed visual
      acuity of 0,08 without correction in right and 0.7 with -5.0 Dsph and -1.0 Dcyl
      Axx 109 degrees  in left eye. Opthalmologic examination showed bilateral aniridia
      associated with moderate cataract in the right and incipient cataract in the left
      eye. In the right eye, zonular weakness with incipient capsular displacement and
      esotropia of Delta6o, were noted. The patient underwent phacoemulsification,
      implantation of capsular tension ring and Artificial Iris implant in the capsular
      bag. Phacoemulsification went uneventful and early postoperative recovery was
      successful with no signs of aniridia-associated keratopathy development and
      normal values of intra ocular pressure. Patient was not motivated for operation
      of the left eye and it was corrected with soft contact lens. Six month after the
      operation visual acuity in the right eye improved to 0.9 with +1.25Dsph and
      maintained stable in left eye, with complete elimination of esotropia and signs
      of binocular vision restoration. Small incision cataract extraction with IOL and
      Artificial Iris implantation in one procedure can be used to correct congenital
      aniridia and cataract with significant visual function improvement. 

PMID- 25568538
TI  - Surgical treatment of left ventricular pseudoaneurysm.
AB  - INTRODUCTION: Left ventricular pseudoaneurysm is a rare condition because in most
      instances ventricular free-wall rupture leads to fatal pericardial tamponade.
      Rupture of the free wall of the left ventricle is a cata-strophic complication of
      myocardial infarction, occurring in approximately 4% of pa-tients with infarcts,
      resulting in immediate collapse of the patient and electromechanical
      dissociation. In rare cases the rupture is contained by pericardial and fibrous
      tissue, and the result is a pseudoaneurysm. The left ventricular pseudoaneurysm
      contains only pericardial and fibrous elements in its wall-no myocardial tissue.
      Because such aneurysms have a strong tendency to rupture, this disorder may lead
      to death if it is left surgically untreated. CASE REPORT: In this case report, we
      present a patient who underwent successful repair of a left ventricular
      pseudoaneurysm, which followed a myocardial infarction that was caused by
      occlusion of the left circumflex coronary artery. Although repair of left
      ventricular pseudoaneurysm is still a surgical challenge, it can be performed
      with acceptable results in most patients.

PMID- 25568539
TI  - Posterior Reversible Encephalopathy Syndrome (PRES) as a Complication of
      Immunosuppressive Therapy in Renal Transplantation in Children.
AB  - Although kidney transplantation is by far the best method of renal replacement
      therapy, organ receiver is still not spared of eventual toxic consequences of
      drugs that are in charge of keeping the transplanted kidney functional. Both
      calcineurin inhibitors, of which tacrolimus more often, occasionally lead to
      neurotoxic side effects, mostly mild and reversible and dose-dependent in nature,
      but they can also be very severe or even fatal. It is very important to be aware
      of possible neurotoxic effects, to confirm them radiologically, and to prevent or
      reduce drug effects on nervous system. Sometimes the reduction of dose or
      substitution with another drug with similar mechanism effect is sufficient to
      terminate the neurotoxic effects of the drug and still not jeopardize the
      function of transplanted organ. 

PMID- 25568541
TI  - A new example of unethical behaviour in the academic journal "medical archives".

PMID- 25568540
TI  - Multiple colon polyposis.
AB  - INTRODUCTION: Familial adenomatous polyposis (FAP) is a rare autosomal, dominant
      hereditary disease, which affects both sexes equally (1-10). FAP accounts for
      less than 1% of all colon cancers and is estimated to occur in one of 8,300 live
      births. It is characterized by numerous adenomas scattered throughout mucosa of
      the colon and rectum. CASE REPORT: The patient is a 62 years old man, admitted at
      the Surgical Department of the General Hospital in Konjic on May 18 2010 with
      gastrointestinal problems including: hard stool, often splattered with fresh
      blood, irregular and that causes the patient a lot of problems. The final
      diagnosis was median laparatomy supra et infraumibilicalis. Exploratio cavi
      abdominalis. Colectomy totalis et ileo-recto anastomosis TT cum staypler (33Ch).
      Loop ileostomy. Drainage cavi abdominalis N I (uno). Early postoperative course
      was generally regular. Control laboratory findings show the reference value.
      After ten days of hospitalization, the patient was discharged on the home
      recovery, with practically given instructions for care and use of stoma bags. For
      the secondary surgery was planned ileostomy closure, and regular post-operative
      endoscopic control. CONCLUSION: Most of the listed surgical intervention in case
      of FAP treatment localized in the colon can be performed by open (classic), or
      laparoscopic methods. Duration of postoperative stay in the hospital depends on
      the patient's general condition and the type of performed surgery. It is usually
      about 7 days. After hospital treatment, recovery at home is from 4-6 weeks.
      Patients can usually return to work or school 6-8 weeks after surgery. After
      surgery, patients lives will be completely normal. Sexual and social activities
      remain the same, while either procedure does not affect the ability of a man or
      woman to have offspring.

PMID- 25568542
TI  - Reduction of pulmonary function after surgical lung resections of different
      volume.
AB  - INTRODUCTION: In recent years an increasing number of lung resections are being
      done because of the rising prevalence of lung cancer that occurs mainly in
      patients with limited lung function, what is caused with common etiologic factor 
      smoking cigarettes. OBJECTIVE: To determine how big the loss of lung function is
      after surgical resection of lung of different range. METHODS: The study was done
      on 58 patients operated at the Clinic for thoracic surgery KCU Sarajevo,
      previously treated at the Clinic for pulmonary diseases "Podhrastovi" in the
      period from 01.06.2012. to 01.06.2014. The following resections were done:
      pulmectomy (left, right), lobectomy (upper, lower: left and right). The values of
      postoperative pulmonary function were compared with preoperative ones. As a
      parameter of lung function we used FEV1 (forced expiratory volume in one second),
      and changes in FEV1 are expressed in liters and in percentage of the recorded
      preoperative and normal values of FEV1. Measurements of lung function were
      performed seven days before and 2 months after surgery. RESULTS: Postoperative
      FEV1 was decreased compared to preoperative values. After pulmectomy the maximum
      reduction of FEV1 was 44%, and after lobectomy it was 22% of the preoperative
      values. CONCLUSION: Patients with airway obstruction are limited in their daily
      life before the surgery, and an additional loss of lung tissue after resection
      contributes to their inability. Potential benefits of lung resection surgery
      should be balanced in relation to postoperative morbidity and mortality.

PMID- 25568543
TI  - Immunophenotype lymphocyte of peripheral blood in patients with psoriasis.
AB  - INTRODUCTION: Regulatory T cells (Treg) play a central role in the
      immunopathogenesis of psoriasis. Immunoregulatory T cells (Tregs) are involved in
      important homeostatic mechanism for maintaining tolerance and preventing
      autoimmunity, and autoimmune diseases. The aim of this study was to examine the
      role of Tregs cells in the pathogenesis of psoriasis, and determine the range
      value for Treg cells (CD4+ CD25+) in the peripheral blood of patients with
      psoriasis compared to the severity of disease. MATERIAL AND METHODS: The study
      included 51 patients diagnosed with psoriasis and 25 healthy individuals.
      Phenotype profile of peripheral blood lymphocytes was determined by flow
      cytometry, and assessment of severity of disease was determined on the basis of
      PASI score (e.g. Psoriasis Area and Severity Index). RESULTS: Proportion of
      CD4+CD25+T cells in the control group was significantly higher than in the
      patients with psoriasis [6,4% +/-(5,4-7,6) vs. 4,1% (3,1 -5,8)-Mann-Whitney U
      test, p <0.001]. In the present study we did not find a statistically significant
      correlation between the levels of CD4+CD25+cells, in patients with psoriasis,
      compared to the severity of disease-PASI. (i.e. Pearson correlation, r = 0.197, p
      = 0.194). CONCLUSION: The stratification of patients, according to the severity
      of the clinical course was not possible on the basis of Treg cells' level. ROC
      curve analysis of the optimal cutoff (PASI=10) and the CD4+CD25+, which
      distinguishes between patients and healthy individuals was 5% of CD4+CD25+ of the
      total number of CD4+ lymphocytes with specificity of 69% and sensitivity of 84%.

PMID- 25568545
TI  - Surgical treatment of inflammatory abdominal aortic aneurysms: outcome and
      predictors analysis.
AB  - OBJECTIVES: The aim of this study is to report our experience on the
      postoperative outcome of surgical treatment of inflammatory abdominal aortic
      aneurysm (IAAA). MATERIALS AND METHODS: Between 1997-2014, 35 patients with IAAA
      underwent surgery. The mean age was 63+/-18years. Chronic renal failure was
      identified in 11(31.4%)patients and confirmed ischemic heart disease in
      15(43%)patients. The mean aortic aneurysm diameter was 68+/-25mm. The abdominal
      aorta was clamped above the renal arteries in 6 (17%) patients. RESULTS: The
      hospital mortality was 5.7% (2 patients). Three patients developed an aortic
      pseudoaneurysm and underwent a redo operation. Another patient developed a
      femoral anastomotic pseudoaneurysm 7 years after operation and he was treated
      surgically. The actuarial free-reoperation actuarial survival at 1, 5 and 7 years
      was 94%, 62% and 50% respectively. The Cox model revealed the delta ESR
      (p=0.002), ischemic heart disease (p=0.006) and renal failure (p=0.036) as strong
      predictors for poor overall outcome. CONCLUSION: Early postoperative outcome in
      terms of mortality and morbidity seems acceptable, however patients with IAAA
      have an increased risk for reoperation due to pseudonaneurysm formation. Strong
      predictors for poor overall outcome seems to be the elevated erythrocyte
      sedimentation rate, ischemic heart disease and chronic renal failure.

PMID- 25568544
TI  - Bacterial uropathogens isolates and antibiograms in children under 5 years of
      age.
AB  - BACKGROUND: Childhood urinary infections are among the most common febrile
      illnesses occurring during this period with varying susceptibility to antibiotic.
      AIM: The aim of this study was to identify uropathogens responsible to for
      urinarytract infection (UTIs) in children less than 5 years of age, and determine
      the antibiograms of the isolates to commonly used antibiotics. PATIENTS AND
      METHODS: Hundred and four children (2 months - 5 years old) seen at the Gadarif
      Teaching Hospital from January 2012 and December 2013 were evaluated. A urine
      specimen was obtained by a plastic bag with an adhesive backing around an opening
      or by direct voiding into sterile container. Urine was examined microscopically
      and those with significant pyuria and bacteruria were further cultured and
      microorganisms were identified and tested for antimicrobial susceptibility.
      RESULTS: Out of 304 children suffering from UTIs; 145(47.7%) had significant
      pyuria of them; 54(17.8 %) had positive bacterial growth. The frequency of sex
      and residency were almost the same. E. coli (42.6%) was the most common
      uropathogen, sensitive to ciprofloxacin (91.3%), followed by Pseudomonas
      aeruginosa (29.6%) sensitive to Ciprofloxacin (75%)and Norofloxacin (68.8%),
      Klebsiellapneumoniae (18.5%) sensitive to Ciprofloxacin and Norofloxacin and
      Nalidixic acid (90%) and Proteus mirabilis sensitive to Ciprofloxacin and
      Norofloxacin (90%), Amoxicillin / clavulanic acid (Augmentin(80%). CONCLUSION:
      The most common uropathogens were E. coli, Pseudomonas
      aeruginosa,Klebsiellapneumoniae, and Proteus mirabilis. Ciprofloxacin is the
      recommended initial empirical therapy while awaiting the culture and sensitivity
      results.

PMID- 25568546
TI  - Risk factors analysis for occurrence of asymptomatic bacteriuria after
      endourological procedures.
AB  - INTRODUCTION: Endourological procedures are performed according to the principles
      of aseptic techniques, jet still in certain number of patients urinary tract
      infections may occur. Considering the risk of urinary tract infection, there is
      no unique opinion about the prophylactic use of antibiotics in endourological
      procedures. GOAL: The objective of this study was to determine the connection
      between endourological procedures and occurrence of urinary infections and to
      analyze the risk factors of urinary infection for patients who were hospitalized
      at the Urology Clinic of the Clinical Center University of Sarajevo CCUS.
      MATERIALS AND METHODS: The research was conducted as a prospective study on a
      sample of 208 patients of both genders, who were hospitalized at the Urology
      Clinic of the CCUS and to whom some endourological procedure was indicated for
      diagnostic or therapeutic purposes. We analyzed data from patient's histories of
      illness, laboratory tests taken at admission and after endourological procedures,
      also surgical programs for endoscopic procedures. All patients were clinically
      examined prior to endoscopic procedures while after the treatment attention was
      focused to the symptoms of urinary tract infections. RESULTS: Statistical
      analysis of the tested patients indicates that there is no significant difference
      in the presence of postoperative, compared to preoperative bacteriuria, which
      implies that the endourological procedures are safe procedures in terms of
      urinary tract infections. Preoperatively, the most commonly isolated bacteria was
      Escherichia coli (30.9%) and postoperatively, Enterococcus faecalis (25%).
      Statistically significant effect on the occurrence of postoperative bacteriuria
      has preoperative bacteriuria, duration of postoperative catheterization, and
      duration of hospitalization. CONCLUSION: In everyday urological practice, it is
      very important to identify and control risk factors for the development of
      urinary infection after endourological procedures, with main objective to
      minimize occurrence of infectious complications.

PMID- 25568548
TI  - Calcium and dairy products consumption and association with total hip bone
      mineral density in women from kosovo.
AB  - BACKGROUND AND OBJECTIVE: There is paucity of evidence in southeastern Europe and
      Kosovo regarding dairy products consumption and association with bone mineral
      density (BMD). Therefore, the objective of present study was to assess calcium
      intake and dairy products consumption and to investigate relationship with total
      hip BMD in a Kosovo women sample. METHODS: This cross-sectional study included a
      sample of 185 women divided into respective groups according to total hip BMD.
      All the study participants completed a food frequency questionnaire and underwent
      dual-energy X-ray absorptiometry (DEXA) to estimate BMD. Nonparametric tests were
      performed to compare characteristics of the groups. RESULTS: The average dietary
      calcium intake was 818.41 mg/day. Only 16.75% of the subjects met calcium
      recommended dietary reference intakes (DRIs). There were no significant
      differences between low BMD group and normal BMD group regarding average dietary
      calcium intake, but it was significantly higher in BMDT3 subgroup than in BMDT2
      and BMDT1 subgroups. CONCLUSIONS: The results of this study demonstrate
      significant relationship of daily dietary calcium intake with upper BMD tertile.
      Further initiatives are warranted from this study to highlight the importance of
      nutrition education.

PMID- 25568547
TI  - The effect of clinical, radiographic and functional scores on the total score in
      the evaluation of congenital clubfoot.
AB  - INTRODUCTION: The use of radical surgical treatments in treating congenital
      clubfoot is decreasing. Minimally invasive surgical treatment (MIST) is a way of
      treating congenital clubfoot, which is a kind of compromise between a radical
      surgical treatment and non-operational one. A few protocols of different authors
      McKay, Macnicol, Stevens, Meyer, G.W.Simons and Laaveg-Ponseti were used in the
      evaluation of the results. SCIENTIFIC OBJECTIVE: To determine the importance and
      role of groups of parameters (clinical, radiographic and functional) in the
      evaluation of the results in patients treated with the two methods (radical
      operation and MIST). SUBJECTS AND METHODS: This paper covers children who were
      treated for structural (idiopathic) form of PEVC. The testing is a prospective
      study and was conducted in two groups of patients. Group A (radical surgical
      treatment) - control group, where the total number of subjects was 50, out of
      which 35 male (70%) and 15 female (30%). The number of feet tested was 88. Group
      B (minimally invasive surgical treatment-MIST)-experimental group. The total
      number of subjects was 48, out of which 35 male (73%) and 13 female (27%). The
      number of feet tested was 84. For the analysis of the results, we used a
      questionnaire. The total number of parameters was fifteen, clinical, radiographic
      and functional, five parameters of each. Normal findings or measured value was
      determined by 0 points. The range of the total score (TS-a- total score range) 0
      27 points, and the results were sorted out into the folowing categories: good
      result (0-5) satisfactory (6-11), poor (12-19) and deformity recrudescence (20
      27) points. RESULTS: The proportion of good results at 88 feet in group A was
      0,477 as at 84 feet in group B it was significantly higher and came to 0,893. The
      difference between these proportions is statistically highly significant (t =
      5.84, p <0.001). Chi-square test (chi2 = 30.083 df = 1 N = 172, p <0.001)
      indicated that there is a highly significant correlation between the method of
      treatment used and results of treatment. Good results of treatment in group A
      were observed in 48% and in group B in 88% of cases. The Charles Spearman
      nonparametric method showed that the rank correlation coefficients for the group
      A are positive, quite high (between 0.70 and 0.85), similar and statistically
      highly significant (p <0.001). The influence of radiographic scores on the total
      score is the lowest, and clinical score on the overall score is the highest. Rank
      correlation coefficients for group B were also positive but somewhat smaller than
      in group A (between 0.55 and 0.75) and statistically highly significant (p
      <0.001). It is possible to notice the difference here and say that the impact of
      functional scores on the total score is the highest and of radiographic score the
      lowest. CONCLUSION: Minimally invasive surgical treatment (MIST) gives better
      functional results in the treatment of congenital clubfoot than radical surgical
      treatment. The role of radigraphic parameters in the evaluation of the results of
      the treatment was the slightest regardless of whether the treatment was radical
      surgery or MIST. We believe that radiography for routine analysis of the results
      of treatment need not be used.

PMID- 25568550
TI  - Short-term Parameters of Heart Rate Variability During Balanced Anaesthesia with
      Administration of Two Different Inhalation Anaesthetics.
AB  - INTRODUCTION: Heart rate variability which denotes variations of the length of
      consecutive heart cycles has been suggested to reflect the modulation of heart
      rate by autonomic nervous system. METHODS: Sixty four patients of ASA I and ASA
      II status scheduled for elective abdominal surgical procedures were randomly
      allocated to group 1 and group 2. Premedication and induction of anaesthesia were
      performed with same agents. After orotracheal intubation maintenance of balanced
      anaesthesia was based on administration of same induction agents,opioids and
      muscle relaxant while delivery of gaseous mixture with sevoflurane in the group 1
      (n=32) and isoflurane in the group 2(n=32). Haemodynamic parameters were
      monitored in perioperative and electrocardiogram was recorded by holter ECG
      recorder, while the analysis of the parameters were performed by corresponding
      softwares . Data were presented as mean values of logarithmic (natural logarithm)
      values of the power of the total spectrum of heart rate variability(TP), mean
      values of the logarithmic values of low frequency band (LF), mean values of the
      logarithmic values of high frequency range(HF), and mean values of SD1 and SD2
      parameters. RESULTS: Analysis of the values of hemodynamic parameters has shown
      changes of haemodynamic parameters during perioperative period without
      significant statistical differences between the groups. Analysis of the
      logarhitmic values of parameters of heart rate variability of frequency domain
      has shown changes of the total spectrum power and LF and HF spestra with
      variations of the values of total power spectrum and individual components of the
      spectrum of heart rate variability during the balanced anaesthesia with
      administration of two different inhalation anaesthetics, without statistically
      significant differences between the groups. CONCLUSION: The results have shown
      that during balanced anaesthesia with two different inhalation anaesthetics there
      are variations of haemodynamic variables and parameters of heart rate variability
      without statistically significance that could show the difference between the
      groups and different agents administered.

PMID- 25568549
TI  - Malnutrition at the time of surgery affects negatively the clinical outcome of
      critically ill patients with gastrointestinal cancer.
AB  - INTRODUCTION: Malnutrition is a frequent concomitant of surgical illness,
      especially in gastrointestinal cancer surgery. The aim of the study was to assess
      the prevalence of malnutrition in the GI cancer patients and its relation with
      clinical outcome. We also examined associations between the energy balance and
      clinical outcomes in these patients. METHODS: Prospective study on 694 surgical
      patients treated in the ICU of the UHC of Tirana. Patients were divided into well
      nourished and malnourished groups according to their nutritional status. Multiple
      regression analysis was used to analyze the effect of malnutrition and cumulated
      energy balance on clinical outcome. RESULTS: The prevalence of pre-operative
      malnutrition was 65.3% for all surgical patients and 84.9% for gastrointestinal
      cancer patients. Malnutrition, as analyzed by a multivariate logistic regression
      model, is an independent risk factor for higher complications, infections, and
      mortality, longer stay in the ventilator and ICU. Also this model showed that
      cumulated energy balance correlated with infections, and mortality and was
      independently associated with the length ventilator and ICU stay. CONCLUSION:
      This study shows that malnutrition is a significant problem in surgical patients,
      especially in patients with gastrointestinal cancer. Malnutrition and cumulated
      energy deficit in gastro-intestinal surgery patients with malignancy is an
      independent risk factor on increased post-operative morbidity and mortality.

PMID- 25568551
TI  - Correlation of serum and ionized calcium in patients with calcium
      nephrolithiasis.
AB  - INTRODUCTION: Pathogenesis of kidney stones includes many factors, whereas
      uroliths, as a generic term for kidney stones, are of a different composition. In
      pathogenesis of calcium urolithiasis hypercalcemia/hypercalciuria takes a
      significant place. Hypercalcemia exists when the serum calcium is of increased
      values, along with measurement and calculation of physiologically active calcium,
      when there are differences in the Ph of the blood or albumin. GOAL: the goal of
      this research is to determine the correlation of values of the serum (CaS) and
      ionized calcium (Ca++) in patients with the calcium nephrolithiasis, whom have
      been established not to have hyperparathyroidism and malign diseases. MATERIAL
      AND METHODS: the research was prospective and implemented at the Clinical Center
      in Banja Luka, at the Urology Clinic, in the period between 1(st) April 2012 -
      1(st) January 2013 and it included 120 patients with the calcium lithiasis of the
      upper part of the urinary tract, divided into three age categories. Diagnosis of
      the calcium lithiasis of the upper part of the urinary tract was established on
      the basis of the ultrasonography of the urinary tract as well as native urinary
      tract/intravenous urography and chemical analysis of the stone in patients with
      spontaneous stone emission or after some of the methods for active removal of the
      stone. Chemical laboratory analysis of the serum and ionized calcium was done for
      all the patients, with 3ml of blood being taken for establishing the
      aforementioned parameters (1-2 ml of the serum) in vacuumed test tubes or glass
      tubes of capillary blood. Increased parathormone values (PHT) and history of
      malignity were excluding factors. RESULTS: out of the 120 patients observed,
      Cs(S) had the value in the reference interval with most of them, that is, in 110
      patients (91.7%). Those, whose value was out of the interval, are of an older age
      (all above 40). Average value of this parameter amounted to 2.3017, with an
      average difference (the standard deviation) of 0.11391. Observing the value of
      Ca++, the value within the reference interval was found in 106 patients (88.3%).
      Out of the remaining 14 patients, only two simultaneously had the value of Ca(S)
      out of the permitted interval. The majority of this group consisted of older
      patients (a half of those whose values were outside the interval was over 60).
      Average value of Ca++ amounted to 1.22 mmol/L with an average difference of
      0.06454. In the 2 aforementioned patients, who simultaneously had increased
      values of CaS and Ca++, the blood Ph was within the referential value limits,
      which suggests that, in line with the hyporcalcemia definition, only 2 patients
      with nephrolithiasis, in the total sample of 120 patients of our research sample,
      could have had a true hypercalcemia. CONCLUSION: the biggest number of patients
      with the calcium urolithiasis, who do not have hyperparathyroidism and history of
      malign diseases, do not have a real hypercalcemia.

PMID- 25568552
TI  - Epidemiology of herpes human virus 6 and 7 infections in salivary gland neoplasms
      in isfahan, iran.
AB  - BACKGROUND: The previous studies showed that herpes human virus-6 (HHV-6) and HHV
      7 exist in salivary glands. One of the important areas in oral and maxillofacial
      pathology field is tumors of the salivary glands. In this study, to declare the
      major sites of persistent infection with HHV-6 and HHV-7, the existence of HHV-6
      and HHV-7 genomes in formalin-fixed paraffin embedded tissue samples of salivary
      gland tumors. METHODS: This analytical study was performed in 60 paraffin blocks
      samples of malignant and benign neoplasms of both major and minor salivary
      glands. This study performed with highly sensitive real time PCR method. RESULTS:
      Among 60 paraffin blocks salivary gland tumors with equal chances of presence of
      the HHV-7 and HHV-6 in the samples, 34% were positive for both HHV-7 and HHV-6
      while 47.2% were only positive for HHV-7, 18.9% samples were positive for HHV-6.
      A relationship was noticed between HHV-7 and HHV-6 genomes. CONCLUSION: In
      conclusion, this study showed no relation between virus and diseases with
      P=0.953. Also it could be inferred that there is a relationship between HHV-6 and
      7 in salivary glands neoplasms.

PMID- 25568553
TI  - Comparison of hydroxyethyl starch 6% and crystalloids for preloading in elective
      caesarean section under spinal anesthesia.
AB  - BACKGROUND: Although controversial, many studies have shown effectiveness of
      colloid loading as a substitute for crystalloids on reducing the incidence of
      hypotension in spinal anesthesia. This study was conducted to compare the effects
      of three intravenous fluid regimens on hemodynamic changes following spinal
      anesthesia in cesarean section. The regimens included 6% Hydroxyethylstarch
      130/0.4 (HES) as a colloid and two crystalloids (lactated ringer's solution and
      sodium chloride 0.9%). MATERIAL & METHOD: In a double-blind clinical trial, 90
      otherwise healthy parturients candidate of elective caesarean section were
      randomly allocated to receive lactated ringer's solution (1000 ml), sodium
      chloride 0.9% (1000 ml) or HES (7.5 mL/Kg) as preloading before spinal
      anesthesia. Hemodynamic parameters including blood pressure and heart rate,
      umbilical cord blood pH and the neonatal Apgar score were compared among the
      three groups. RESULTS: There was no difference in the basic hemodynamic
      measurements among the three groups. The incidence of hypotension and required
      dose of ephedrine was lower in HES group (p=0.008). There was no significant
      difference in umbilical cord blood PH or Apgar scores among intervention groups.
      CONCLUSION: Preloading with HES is more effective than crystalloids in prevention
      hypotension after spinal anesthesia without significant difference in Apgar score
      and umblical cord blood pH.

PMID- 25568554
TI  - The importance of heart murmur in the neonatal period and justification of
      echocardiographic review.
AB  - INTRODUCTION: Heart murmurs can be functional (innocent) and pathological
      (organic). Although it is not considered a major sign of heart disease, it may be
      a sign of a serious heart defect. In most cases the noise is initiation for
      cardiac treatment. Is it possible to differentiate on the basis of auscultation
      innocent from pathological heart murmur? In this article we present the results
      of ultrasonography of newborns with positive auscultation finding of the heart in
      the neonatal and early infancy period. GOAL: To determine the role of murmurs in
      the heart detected by routine clinical examination in the neonatal period and
      early infancy, and to establish the legitimacy of cardiology consultation and
      ultrasound of the heart. METHODS: A retrospective review of medical records in
      the period from January 1 to December 31, 2011 at the Maternity ward of Cantonal
      Hospital in Bihac 1899 children was born. In 32 neonates was registered a heart
      murmur, in the period from birth up to 6 weeks of life. All children with
      positive auscultation finding of the heart were examined echocardiography by
      ultrasound ALOCA 2000, multifrequency probe from 3.5 to 5 MHz, and used M-mode, 2
      D, continuous, pulsed and color Doppler. RESULTS: Of the 32 examined children
      regular echocardiographic findings had two children (6.25%), aberrant bunch of
      left ventricle 11 (34.37%), patent foramen ovale 5 (15.62%), atrial septal defect
      3 children (9.37%), ventricular septal defect 8 children (25%), cyanogen anomaly
      2 children (6.25%), stenosis of the pulmonary artery 1 child (3.12%). We see that
      14 children (43.75%) had a structural abnormality of the heart that requires
      further treatment and monitoring. CONCLUSION: Echocardiography is necessary to
      set up or refute the diagnosis of structural heart defect in children with
      positive auscultation finding in the neonatal period.

PMID- 25568555
TI  - Treatment of patients with tiolox-dentaurum dental implants at the polyclinic
      shoshi.
AB  - INTRODUCTION: The importance of the dental implantology has influenced the
      development of many treatment methods in this field. The aim of our study is to
      evaluate the advantages and disadvantages of the treatment with TIOLOX-DENTAURUM
      dental implants in cases of partial and total lack of teeth, compared to classic
      dentures. To conduct our research we have used the prospective method. MATERIAL
      AND METHODS: The analyzed cases have undergone surgical treatment at the
      "Policlinic Shoshi" in Prishtina during 2010-2011. This study included 29
      patients, 23 in the research group and 6 in the control group. The patients
      involved in the study were 30-59 years old. 52,2% of our patients were 30-39
      years old, while 17,4% were 50-59 years old. RESULTS: In the research group, the
      average time of placing the dental bridges in the lower jaw was 2 months and 4.2
      months in the control group. In the upper jaw, the average time was 3 months for
      the experimental group and 5,4 months for the control group. CONCLUSION: The
      period after the placement of implants until the placement of dentures, can be
      shortened from 4-6 months to 3 months for the upper jaw and from 3 to 2 months
      for the lower jaw.

PMID- 25568556
TI  - Cyst of the canal of nuck in a two year old girl.
AB  - The canal of Nuck is analogous to a patent processus vaginalis in a male, which
      normally loses its communication to the peritoneal cavity within the first year
      of life. Failure of obliteration of this tract can result in a hydrocele. We
      present a rare case of a 2-year-old girl with left-sided groin swelling,
      diagnosed as inguinal hernia. Patient underwent surgical exploration and
      establishes definitive diagnosis as cyst of the canal of Nuck. 

PMID- 25568557
TI  - Iatrogenic injury to the common bile duct.
AB  - INTRODUCTION: The formation of gallstones in the gall bladder is very common. It
      is now considered that approximately 10% to 15% of the adult population has
      gallstones. It is more frequent in women than men. ETIOLOGIES ARE VARIOUS AND
      INCLUDE: age, sex, diet, sudden weight loss, etc. According to the report of the
      US National Institute of Health, it is estimated that 6.3 million men and 14.2
      million women, aged 20-74 years in the United States has calculosis of the
      gallbladder, due to which every year is performed about 700,000 cholecystectomy.
      CASE REPORT: Male patient, aged about 40 years, admitted at the Clinic and
      laparoscopic surgery was performed in our department for chronic, as multiple,
      symptomatic gallbladder calculi. Intraoperative findings showed chronically
      inflamed, curled gall bladder, and wall thickening. After the first postoperative
      day there is no content in the drain bag and it is taken out, and the patient
      leaves the hospital without any problems. The seventh post-operative day occurred
      abdominal pain, weakness and fatigue, with striking yellow skin and visible
      mucous membranes. Clinical, laboratory and echo determined abdomen full of
      fluids, so it was suspected lesion of the bile duct. Urgent revision was
      performed. Intraoperative was found a lesion of the common bile duct in the form
      of a complete interruption. Created is anastomosis through transhepatic drain
      according to Pradera. Early and late postoperative flow was entirely normal with
      normal laboratory and echofindings. Control, contrast imaging through a drain
      showed the orderly flow of extrahepatic bile ducts, with minimal extravasation of
      contrast. CONCLUSION: At the Department of Surgery of General Hospital in Konjic
      laparoscopic cholecystectomy is performed since 1999. In the beginning it was
      done by three trocars (European style), and later, in order to prevent
      complications or injury of the bile duct is performed surgery with four trocars
      (American style). The number of complicated procedures in our hospital does not
      differ from similar indicators in foreign surgical facilities.

PMID- 25568558
TI  - Complications Related to Insertion and Use of Central Venous Catheters (CVC).
AB  - INTRODUCTION: Central Venous Catheters (CVC) are essential in everyday medical
      practice, especially in treating patients in intensive care units (ICU). The
      application of these catheters is accompanied with the risk of complications,
      such as the complications caused during the CVC insertion, infections at the
      location of the insertion, and complications during the use of the catheter,
      sepsis and other metastatic infections. PATIENTS AND METHODS: This study is a
      retrospective-prospective and it was implemented in the period 1(st) January 2011
      31(st) December 2012. It included 108 examinees with CVC placed for more than 7
      days. RESULTS: The most common complications occurring in more than 2 attempts of
      CVC applications are: hearth arrhythmias in both groups in 12 cases, 7 in multi
      lumen (12.72%) and 5 in mono-lumen ones (9.43%). Artery puncture occurs in both
      groups in 7 cases, 5 in multi-lumen (9.09%) and 2 in mono-lumen ones (3.77%).
      Hematoma occurred in both groups in 4 cases, 3 in multi-lumen CVCs (5.45%) and 1
      in mono-lumen ones (1.88%). The most common complication in multi-lumen catheters
      was heart arrhythmia, in 20 cases (36.37%). The most common complications in mono
      lumen CVCs was hearth arrhythmias, in 20 cases as extrasystoles and they were
      registered in 16 catheter insertions (30.18%). Out of total number of catheters
      of both groups, out of 108 catheters the complications during insertion occurred
      in 49 catheters (45.40%). The most common complications in both groups were heart
      arrhythmias, artery punctures and hematomas at the place of catheter insertion.

PMID- 25568559
TI  - The usefulness of clinical and laboratory parameters for predicting severity of
      dehydration in children with acute gastroenteritis.
AB  - BACKGROUND: An accurate assessment of the degree of dehydration in infants and
      children is important for proper decision-making and treatment. This emphasizes
      the need for laboratory tests to improve the accuracy of clinical assessment of
      dehydration. The aim of this study was to assess the relationship between
      clinical and laboratory parameters in the assessment of dehydration. METHODS: We
      evaluated prospectively 200 children aged 1 month to 5 years who presented with
      diarrhea, vomiting or both. Dehydration assessment was done following a known
      clinical scheme. RESULTS: We enrolled in the study 200 children (57.5% were
      male). The mean age was 15.62+/-9.03 months, with more than half those studied
      being under 24 months old. Overall, 46.5% (93) had mild dehydration, 34% (68) had
      moderate dehydration, 5.5% (11) had severe dehydration whereas, 14% (28) had no
      dehydration. Patients historical clinical variables in all dehydration groups did
      not differ significantly regarding age, sex, fever, frequency of vomiting,
      duration of diarrhea and vomiting, while there was a trend toward severe
      dehydration in children with more frequent diarrhea (p=0.004). Serum urea and
      creatinine cannot discriminate between mild and moderate dehydration but they
      showed a good specificity for severe dehydration of 99% and 100% respectively.
      Serum bicarbonates and base excess decreased significantly with a degree of
      dehydration and can discriminate between all dehydration groups (P<0.001).
      CONCLUSION: Blood gases were useful to diagnose the degree of dehydration status
      among children presenting with acute gastroenteritis. Serum urea and creatinine
      were the most specific tests for severe dehydration diagnosis. Historical
      clinical patterns apart from frequency of diarrhea did not correlate with
      dehydration status. Further studies are needed to validate our results.

PMID- 25568560
TI  - Clinical Effects of Rhus coriaria Fruits on Dyslipidemia308 in Adolescents: a
      Triple-blinded Randomized Placebo-controlled Trial.
AB  - OBJECTIVE: Children and adolescents are considered as the best target groups for
      preventing and controlling the cardiovascular diseases risk factors and reducing
      mortality in adulthood. Alternative medicine and herbal drugs have been taken
      into account for managing dyslipidemia in this population. The beneficial effects
      of Sumac (Rhus coriaria L.) on lipid profile have been confirmed in some
      laboratory and animal studies. This study was designed to investigate the
      clinical effects of sumac fruits on dyslipidemia in 12-18 years-old adolescents.
      METHODS: This randomized triple-blinded clinical trial was conducted on 72 obese
      adolescents with dyslipidemia from August 2011 to June 2012 in Isfahan
      Cardiovascular Research Center, Isfahan, Iran. Eligible adolescents were randomly
      assigned to two case and control groups. The control group received placebo
      capsules and the case group received capsules containing 500 mg of powdered sumac
      fruits, each three times a day for one month. Biochemical parameters including 12
      hrs fasting serum levels of total cholesterol (Total-C), low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and
      triglycerides (TG) were measured before the initiation and after the completion
      of the study protocol. Statistical analysis was performed using the SPSS
      software, version 16.0, using Independent Samples T-test, or Paired Samples T
      test, for between-group and within-group analysis, respectively. FINDINGS: The
      plasma levels of Total-C, LDL-C, and TG changed significantly over-time in the
      case group. Furthermore, between-group analysis showed a statistically
      significant difference between case and control groups with this regard (P <
      0.05, for all statistical comparisons). However, HDL-C levels have not been
      changed significantly over-time within the case or control group, neither between
      the two study groups. CONCLUSION: In this study, the considerable effects of Rhus
      coriaria (sumac) on reducing serum levels of Total-C, LDL-C, and TG have been
      noticed during one-month trial. However, probably due to the concise period of
      sumac consumption, its effect on HDL-C was not statistically significant.

PMID- 25568561
TI  - Effects of Teraphy with Basal Insulin Analogues Combined with GLP 1 Analogues and
      Metformin in the Treatment of Obese Patients with Poorly Regulated Postprandial
      Glycemia.
AB  - INTRODUCTION: Patient-oriented therapy represents a modern approach in the
      treatment of patients with diabetes, an approach which is supported in the most
      recent guidelines by the ADA and the European Association for the Study of
      Diabetes (EASD). The progressive nature of diabetes demands the introduction of
      insulin therapy much earlier in order to prevent the development of late
      complications of the disease. MATERIAL AND METHODS: The study included 30
      patients who had been treated with long-acting insulin analogue and metformin in
      doses of 3 x 850 mg at least 6 months prior to study entry and in which a good
      glycaemic control had not been achieved, or with HbA1c > 7%. Patients who had a
      BMI > 28 kg /m2 were included in the study. RESULTS AND DISCUSSION: At the
      beginning of the study the patients were switched to combined therapy with long
      acting basal analog, metformin and liraglutide in a dosage of 0.6 mg of 1x1.
      After 12 weeks of the new therapeutic regimen we recorded a significant reduction
      in the parameter levels that we monitored in the study. BMI value after the test
      was 28.2+/-1.39 kg/m2, p=0.025, HbA1c 7.24+/-0.47%, p=0.030, fasting blood
      glucose level 7.04+/-0.32 mmol/l, p=0.023, postprandial glucose level 7.6+/-0.46
      mmol/l, p=0.012, systolic blood pressure level 123+/-5.75 mmHg, p=0.015,
      diastolic blood pressure level 79.1+/-2.91 mmHg, p=0.03. During research that we
      have conducted over 12 weeks, a reduction of body weight was achieved while
      improving the value of parameters significant for the study. CONCLUSION: There
      was a significant lowering of HbA1c, fasting blood glucose levels, postprandial
      glucose levels and better blood pressure control by which we have proved that
      GLP1 analogues in combination with basal insulin and metformin provide a good
      glycaemic control with a cardio protective effect, and reduce the risk of late
      complications.

PMID- 25568562
TI  - Descriptive review of the patients suffering from tuberculosis in the past 10
      years treated at pediatric clinic of clinical center of sarajevo university.
AB  - INTRODUCTION: Due to the geographical position of Bosnia and Herzegovina and its
      socio economic momentum even though the standard vaccination program is carried
      out, the child population continues to suffer from pulmonary tuberculosis in
      significant percentage. MATERIAL AND METHODS: The study was retrospective and
      included patients who were in the period from January 1, 2004 to December 31,
      2013 (or the 10 years period) hospitalized at the Department of Pulmonology
      Pediatric Clinic dually diagnosed with lung TB and start treatment. Data were
      adopted from available medical records (history of disease). GOAL: The aim of the
      study was to determine the epidemiological and clinical characteristics of
      tuberculosis of the lungs in children who were hospitalized at the Pediatric
      Clinic. RESULTS: In the period from January 1, 2004 to December 31, 2013 there
      were hospitalized a total of 50 children with a proven active infection with MBT,
      where it was initiated treatment with a specific therapy. From this number 44% of
      patients were aged from 5 to 10 years, 22% of patients were aged younger than 5
      years. Peak incidence was in 2009. About 66% of patients had a positive history
      of sick close relative, while 10% of them had a history of contact with other
      sick person. From baseline 28% of patients were referred to the Department with
      suspicion of a specific process. From the total 70% of respondents were regularly
      vaccinated, and 29% of them had a visible BCG scar. In 55% of cases there was
      anamnestic information - decresed body weight, in 82% of cases the presence of
      cough, of which 52% of the occurrence of expectoration. In 78% of cases we had
      positive auscultatory findings of the lungs. In 14% of cases on X-ray of the
      lungs was noticed changes in terms of the primary complex positive. In this
      material we had one cavernous and one miliary TB of the lungs. Sputum or gastric
      lavage was positive in 62% of cases, and Quantiferon because of the lack of the
      same (in the past) was positive in 34% of cases. All subjects at the time of
      discharge were classified as recovered. In that period we had proven resistant
      TB. CONCLUSION: Bosnia and Herzegovina belongs to the group of countries with
      still present and evident TB. In the investigated period of ten years from the
      pediatric pulmonary TB, usually have suffered small children and adolescents. At
      moment of discharge, all patients were classified as recovered. In the teste
      material we did not have proven resistant TB.

PMID- 25568563
TI  - Prevalence and genotypes of hepatitis B virus infection in patients underwent
      coronary angiography and coronary artery bypass grafting in mazandaran heart
      center, sari, iran.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a major global health problem in
      the worldwide that associated with significant morbidity and mortality in cardiac
      surgery. The available data on HBV distribution and genotyping of HBV are very
      heterogeneous. Therefore in this study, we tried to indicate the prevalence of
      HBV infections in cardiac catheterization patients referred to health centers in
      the north of Iran and identified the HBV genotypes using polymerase chain
      reaction (PCR). METHODS: In this cross-sectional study, we studied 2650 patients
      who underwent selective coronary artery angiography and coronary artery bypass
      grafting in Mazandaran heart center, Sari, Iran from 2011 to 2013. All serum
      samples were examined to detect HBsAg by ELISA test. HBV-DNA was extracted from
      HBsAg positive samples using Mini Elute Kit from Qiagen and determined the
      genotypes of HBV by PCR using the Master Mix kit with Taq-DNA polymerase enzyme
      and with type of specific primers. All samples were examined in the virology
      laboratory of Sari Medical School. RESULTS: The mean age of patients was 59.7+/
      10.9 (range, 20 to 81) year that 1590 (60%) patients were male and 1060 (40%)
      were female. Seventeen cases (0.08 %) were found with hepatitis B virus
      infection, and the highest rates of infection were reported among those aged 40
      60 years old in this study. We found genotype D the predominant type in this
      study. CONCLUSION: This study indicates that the prevalence of HBV endemicity in
      the north of Iran is low and genotype D is the only genotype in patients infected
      with HBV.

PMID- 25568564
TI  - Correlation between blood lead level and hemoglobin level in mitrovica children.
AB  - INTRODUCTION: Lead toxicity is a serious health threat, especially in developing
      countries due to environmental pollution. It was thus aimed to investigate
      correlation between blood lead level and concentration level of hemoglobin in the
      blood of children involved in research. MATERIAL AND METHODS: The research
      included 250 children of which 31(12.4%) kindergarten children, 166 (66.4%) of
      primary school pupils in Mitrovica and 53(21.2%) of primary school pupils in
      Shtime as control group. From the 250 children included in the survey 129 or
      51.6% were female children and 48.4% male children. Children were selected
      randomly, while tests for concentration of Pb and blood hemoglobin were done at
      the National Institute of Public Health. RESULTS: The average value of blood lead
      level of Mitrovica pupils was 2.4 ug/dL (SD+/-1.9ug/dL), range 0.5 to 16.3ug/dL.
      The average value of blood lead level of Shtime pupils was 2.3ug/dL (SD+/
      0.7ug/dL), range 1.2 to 5.2 ug/dL with no statistical difference (P = 0.191). The
      average value of blood lead level in kindergarten children of Mitrovica was
      3.8ug/dL (SD+/-1.3ug/dL), range 2.2 to 7.7ug/dL with significant difference
      between the average values of blood lead levels of pupils and kindergarten
      children of Mitrovica (P <0.0001). The average value of hemoglobin in the pupils
      of Mitrovica was 14.0g/dL(SD+/- 3.7g/dL), range 9.4 to 25.6 g/dL. The average
      value of hemoglobin to pupils of Shtime was 11.4g/dl(SD+/-0.8 g/dl), range 9.2 to
      13.0 g/dl with significant difference between mean values of hemoglobin pupils of
      Mitrovica and Shtime (U '= 6440.0, P <0.0001). With Spearman correlation is found
      significant correlation of a medium scale (r = -0.305, df = 248, p <0.0001)
      between blood lead levels and hemoglobin level in the blood.

PMID- 25568565
TI  - Epidemiological aspects of atherosclerosis in patients treated for acute
      atherothrombosis of extremity arteries.
AB  - INTRODUCTION: Risk factors for development of extremity artery atherosclerosis
      are the same as for coronary and cerebrovascular atherosclerosis namely, diabetes
      mellitus, hyperlipidemia, arterial hypertension, age and smoking. Atherosclerosis
      is polyarterial disease that clinically manifests itself most frequently in the
      form coronary, cerebrovascular or peripheral arterial disease (PAD). All of them
      have common, ominous and final pathologic step - atherosclerotic plaque rupture
      that might eventually lead to atherothrombosis and signs of ischemia. There are
      few studies of risk factor for peripheral artery disease (PAD). AIM OF STUDY: To
      identify prevalence of known risk factors for atherosclerosis in patients treated
      for acute atherothrombosis of extremity arteries. PATIENTS AND METHODS: Eighty
      patient were analyzed with regard to the prevalence of five risk factors for
      atherosclerosis (diabetes mellitus, smoking, hypertension, hyperlipidemia and
      age). 80 patients were divided into two groups (Group A and B) depending on
      country i.e. hospital where they received treatment for acute atherothrombosis of
      extremity artery. Group A consisted of patients treated at Clinic for vascular
      surgery in Sarajevo, while patients in Group B were treated in Trollhattan in
      Sweden at NAL hospital. This study was clinical, comparative, retrospective
      prospective. RESULTS: In group A, 20% of patients had diabetes mellitus while in
      group B prevalence of diabetics was lower (12,5%) but difference was not
      statistically significant p>0.05. Sixty percent of patients (60%) in group A were
      smokers. In Sweden, habit of smoking is not as common as in Balkan countries and
      consequently only 22,5% of patients were smokers in Group l, difference was
      statistically significant, p<0.05. In patients assigned to group A, 42.5% of them
      had diagnosis of hypertension while in Group B, 35% of patients were
      hypertensive. Difference was not statistically significant, p>0.05. 37.5% of
      patients in group A and 20% of patients in group B had hyperlipidemia. Difference
      was not statistically significant, p>0.05. In Group A mean age of patients was
      67.85 years while mean age in Group B was 73.63. Age difference was statistically
      significant, p<0.05. CONCLUSION: Prevalence of risk factors of atherosclerosis in
      peripheral artery disease were evaluated in this study. Significant difference in
      prevalence of two risk factors were determined namely, smoking and mean age of
      occurrence of atherothrombosis. Quiting smoking and adopting healthier life
      habits may lead to reduction of prevalence PAD in younger patients in Bosnia and
      Herzegovina.

PMID- 25568566
TI  - Improvement of ejection fraction after coronary artery bypass grafting surgery in
      patients with impaired left ventricular function.
AB  - OBJECTIVES: The present study evaluates our experience with aorto-coronary bypass
      grafting in patients with severe dysfunction of left ventricle (LV) and low
      ejection fraction-EF(<35%). Revascularization of myocardium in this settings
      remains contraversial because of concerns over morbidity, mortality and quality
      of life. MATERIAL AND METHODES: Forty patients with severe coronary artery
      disease and dysfunction of LV (low ejection fraction <35%) underwent coronary
      artery bypass grafting in period of 3 years. Preoperative diagnostic of 40
      patients was consisted of anamnesis, clinical exam, non-invasive methods EHO, MR
      and invasive diagnostic methods-cateterization. The major indication for surgery
      was severe anginal pain, heart failure symptoms and low ejection fraction.
      Internal mammary artery was used in all operated patients. RESULTS: Average age
      of patients who have been operated was 59,8. In the present study, 81,3% were
      male and 18,8% female. We found one-vessel disease present in 2,5% (1/40) of
      patients, two -vessel disease in 40% (16/40), three-vessel disease in 42,5%
      (17/40) and four -vessel disease in 15% (6/40) of patients. One bypass grafting
      we implanted in 2,5% patients, two bypasses in 42,5%, three bypasses in 45 5%,
      and four bypasses in 10% of patients. Left ventricular ejection fraction assessed
      preoperativly was 18%-27% and postoperatively was improved to 31, 08% in period
      of 30 days. CONCLUSION: In patients with left ventricular dysfunction, coronary
      artery bypass grafting can be performed safely with improvement in quality of
      life and in left ventricular ejection fraction.

PMID- 25568567
TI  - Incidence of osteoporosis in patients with urolithiasis.
AB  - INTRODUCTION: Clinical researches have shown an increased bone disintegration and
      lower bone mass in patients with calcium urolithiasis. GOAL: The goal of our
      research was to establish the incidence of osteoporosis in adult patients with
      calcium urolithiasis, on the basis of measuring mineral bone density, using DEXA
      method, with a special reflection on age subgroups. MATERIAL AND METHODS:
      Clinical research was prospective and it was implemented at the University
      Clinical Center of Banja Luka, at the Clinic for Endocrinology, Diabetes and
      Metabolic Diseases and at the Urology Clinic. Material in this research consisted
      of patients divided in two groups, a working and a control group. One hundred and
      twenty (120) patients were included in both these groups, divided in three age
      subgroups: 20-40, 40-60 and over 60. The working group consisted of the patients
      with calcium urolithiasis and the control group consisted of patients without
      calcium urolithiasis. Establishing of mineral bone density at L2-L4 of lumbal
      spine vertebrae and hip was done for the patients in both these groups, using
      DEXA method. RESULTS: Analysis of mineral bone density using DEXA method in
      patients in age groups of working and control groups, as well as in the total
      sample of working and control groups, have shown that the patients of the working
      group, over 60, had a decreased mineral bone density (30% of osteopenia and 15%
      osteoporosis) significantly more expressed when compared to the other two age
      groups (12.5% in the subgroup 20-40 and 17.5% in the subgroup 40-60), which
      presents a statistically significant difference (p<0.05). In the control group,
      when taking into account age groups, osteopenia and osteoporosis were marked in
      37.5% and 2.5% in the group of patients over 60, whereas in the youngest
      population, 5% of osteopenia was found, which presents a statistically
      significant difference (p<0.05). When observing the total sample of working and
      control group, there was a statistically significant difference in the working
      and control group (p<0.01); incidence of osteoporosis in the working group
      amounted to 7.5% and in the control group it was 0.8%. CONCLUSION: Urolithiasis
      and osteoporosis are two multifactorial diseases which are evidently reciprocal.
      This is why we suggest that educating the population about the risk factors for
      occurrence of these diseases as well as preventive measures that may contribute
      to their decrease should begin as early as possible.

PMID- 25568568
TI  - Attenuation of Hemodynamic Response to Laryngoscopy and Endotracheal Intubation
      with Pre Induction IV Fentanyl Versus Combination of IV Fentanyl and Sub Lingual
      Nitroglycerin Spray.
AB  - INTRODUCTION: Endotracheal intubation is one of the most invasive stimuli in
      anesthesia and it's often accompanied by a hemodynamic pressor response. The
      purpose of this study was to investigate the efficacy of a single pre-induction 2
      ug/kg bolus injection of fentanyl followed by two puffs of nitroglycerin sub
      lingual spray (400 ug /spray) with a thiopentone/suxamethonium sequence in the
      attenuation of the hemodynamic response to endotracheal intubation in
      normotensive patients. MATERIAL AND METHODS: The study consisted of 80 randomly
      selected ASA physical status I/II male/female adults who were aged between 18
      through 60 years and scheduled for elective surgery. Group I received a single 2
      ug/kg IV bolus of fentanyl diluted to 5 ml with normal saline 5 min prior to
      laryngoscopy followed by two puffs of nitroglycerin sub lingual spray (400
      ug/spray) 2 minutes prior to intubation (n=40). Group II received a single 2
      ug/kg IV bolus of fentanyl diluted to 5 ml with normal saline 5 min prior to
      laryngoscopy (n=40). Heart rate, systolic blood pressure, diastolic blood
      pressure, mean arterial pressure and rate pressure product were compared to basal
      values at pre-induction, induction, intubation and post-intubation as well as at
      time increments of 1, 3, 5, 7 and 10 min. RESULTS: Fentanyl combined with
      nitroglycerin did not attenuate hemodynamic pressor responses more than fentanyl
      alone. Increases of HR (7.9%), DBP (4.0%), MAP (3.6%) and RPP (6.0%) along with
      attenuation of SBP (2.7%) were observed in the fentanyl-nitroglycerin group as
      compared to the equivalent control measured values. CONCLUSIONS: A single pre
      induction bolus injection of fentanyl followed by two puffs of nitroglycerin sub
      lingual spray in a thiopentone/suxamethonium anesthetic sequence neither
      successfully attenuates nor successfully suppresses the hemodynamic pressor
      response more effectively than fentanyl alone in normotensive patients resulting
      from endotracheal intubation.

PMID- 25568569
TI  - Motor evoked potentials in 43 high risk spine deformities.
AB  - INTRODUCTION: Correction of pediatric spine deformities is challenging surgical
      procedures. This fragile group of patients has many risk factors, therefore
      prevention of most fearing complication-paraplegia is extremely important.
      Monitoring of transmission of neurophysiological impulses through motor and
      sensor pathways of spinal cord gives us an insight into cord's function, and
      predicts postoperative neurological status. GOAL: Aim of this work is to present
      our experiences in monitoring of spinal cord motor function - MEP during surgical
      corrections of the hardest pediatric spine deformities, pointing on the most
      dangerous aspects. MATERIAL AND METHODS: We analyzed incidence of MEP changes and
      postoperative neurological status in patients who had major spine correcting
      surgery in period April '11- April '14 on our Spine department. RESULTS: Two of
      43 patients or 4.6% in our group experienced significant MEP changes during their
      major spine reconstructive surgeries. We promptly reduced distractive forces, and
      MEP normalized, and there were no neurological deficit. Neuromonitoring is
      reliable method which allows us to "catch" early signs of neurological deficits,
      when they are still in reversible phase. Although IONM cannot provide complete
      protection of neurological deficit (it reduces risk of paraplegia about 75%), it
      at least afford a comfort to the surgeon being fear free that his patient is
      neurologically intact during long lasting procedures.

PMID- 25568570
TI  - The effects of rehabilitation protocol on functional recovery after anterior
      cruciate ligament reconstruction.
AB  - INTRODUCTION: The use of rehabilitation protocol which corresponds to surgical
      technique results in optimal postoperative outcome and functional recovery of
      patients to a pre-injury level of activity. The aim of this paper is to show the
      effects of the official rehabilitation protocol in our Institute on functional
      recovery of patients after anterior cruciate ligament (ACL) reconstruction.
      PATIENTS AND METHODS: In prospective study, we evaluated 70 males after ACL
      reconstruction using hamstring graft. Patients were divided into two groups
      according to the manner of conducting the postoperative rehabilitation. Group A
      consisted of 35 patients that followed postoperative rehabilitation according to
      the rehabilitation protocol. Group B also 35 patients, which did not undergo the
      rehabilitation protocol. We evaluated thigh muscle circumference and modified
      Tegner Lysholm Score, preoperatively and postoperatively after 1,3,6 and 12
      months. In the statistical analysis, the Studentov T-test was used. RESULTS: In
      the first postoperative month, the difference between groups in thigh muscle
      circumference is statistically significant (p<0,05). This difference between
      groups is statistically highly significant after 3, 6, and 12 months
      postoperative (p<0,01). Results of the modified Tegner Lysholm Score is
      statistically highly significant in 1, 3 and 6 postoperative months in patients
      from the experimental group (p<0,01). CONCLUSION: The positive effects of the
      rehabilitation protocol results in significant increase of the thigh muscle
      circumference and faster functional recovery of patients after ACL
      reconstruction.

PMID- 25568571
TI  - Southwick osteotomy stabilised with external fixator.
AB  - INTRODUCTION: Epiphysiolysis of the femoral head is the most common accident
      occurring towards the end of pre-puberty and puberty growth. CASE REPORT: The
      author describes the experience in the treatment of chronic epiphysiolysis in two
      patients treated by Southwick osteotomy. The site is accessed by way of a 15-cm
      long lateral skin incision and the trochanteric region is reached through the
      layers. The osteotomy angles prepared beforehand on a thin aluminium model are
      used to mark the Southwick osteotomy site on the anterior and lateral sides at
      the level of the lesser trochanter. Before performing the trochanteric osteotomy,
      two Mitkovic convergent pins type M20 are applied distally and proximally, above
      the planned osteotomy site. A tenotomy of the iliopsas muscle is performed, and
      then the previously marked bone triangle is redissected up to three quarters of
      the width of the femur. The distal part of the femur is rotated inwards, so that
      the patella is turned towards the ceiling. The osteotomised fragments of the
      femur are adapted, repositioned and fixated by installing an external fixator on
      the previously placed pins. Two more pins are placed, one proximally and one
      distally, with a view to adequately stabilising the femur. The patient was mobile
      from day two after the surgery. If, after the surgery, the lead surgeon realises
      that there is a requirement to make a correction of 5, 10 and 15 degrees of the
      valgus, varus, anteversion or retroversion deformity, the correction shall be
      performed without surgically opening the patient, using the fixator pins.
      CONCLUSION: After performing a Southwick osteotomy it is easier to adapt,
      reposition and fixate the osteotomised fragments of the femur using a fixator
      type M20. Adequate stability allows regaining mobility quickly, which in turn is
      the best prevention of chondrolysis of the hip. It is possible to make post
      operative valgus, varus, anteversion and retroversion corrections of 5, 10 and 15
      degrees without performing a surgery. Once the osteotomy is healed, the fixator
      type M20 is removed without any additional surgery.

PMID- 25568572
TI  - Mandible bone metastases secondary to pulmonary adenocarcinoma.
AB  - OBJECTIVE: Metastatic tumors of the mandible are rare and usually present
      clinically as growths. The prognosis of lung cancer patients with bone metastases
      is poor. CASE REPORT: This article shows a metastasis from adenocarcinoma of the
      lung affecting the mandible of a 75-year-old female patient where the metastatic
      lesion was detected before primary tumor. The patient were treated with radiation
      therapy with palliative and antalgic intent. But the patient died 8 weeks after
      the diagnosis. CONCLUSION: Radiation therapy was effective and well tolerated in
      the case. Bone metastases particularly mandible metastasis of lung cancer has
      poor prognosis. Palliative and supportive therapy may be firstly chose because of
      poor prognosis.

PMID- 25568573
TI  - Anesthesia management in a patient with kabuki syndrome.
AB  - BACKGROUND AND OBJECTIVES: The aim of this case was to describe the anesthetic
      approach to a patient with Kabuki syndrome. CASE REPORT: A patient with Kabuki
      syndrome had revision surgery for scoliosis. On physical examination, shown were
      long palpebral fissures, large, prominent fissures with an eversion of the
      lateral third of the lower eyelids, large, prominent malformed ears with low
      implantation, a short nasal septum, micrognathia, thoracolumbar scoliosis, a
      depressed left shoulder, a low-set occipital hairline and a short neck. The skin
      was elastic, and joints were lax. The laryngoscopy showed a Grade II Cormack and
      Lehane view of the larynx. The trachea was intubated easily. The patient was
      positioned carefully. Vital signs remained stable during surgery. The patient was
      extubated and transported to the post-anesthetic care unit. CONCLUSION:
      Anesthesiologists should be aware of possibly difficult tracheal intubation
      cardiac lesions, respiratory problems, neurological and musculoskeletal
      disorders, and a latex allergy when managing anesthesia for a patient with Kabuki
      syndrome.

PMID- 25568575
TI  - The Perceptions of Professionalism by 1(st) and 5(th) Grade Medical Students.
AB  - INTRODUCTION: Professionalism is essential for the development of mature
      physicians but not much education is devoted to that theme. AIM: We aimed to
      determine the views of undergraduate medical students on medical professionalism.
      METHODS: This was a qualitative study, based on focus groups of the first and
      fifth-year undergraduate medical students. Transcripts of the focus groups were
      independently evaluated by two researches. Segments of transcripts, identified as
      important, were marked as verbatims. A grounded theory method with open coding
      was applied. A list of codes was developed and reviewed by both researchers until
      the consensus was reached. Then, the codes were reviewed and put into the
      categories and dimensions. RESULTS: Students recognized 10 main medical
      professionalism dimensions (empathy, respect, responsibility, autonomy, trust,
      communication, difference between professional and private life, team work,
      partnership) and two dimensions associated with it (physician's characteristics,
      external factors). Slight change of the attitudes towards a more self-centred
      future physicians' figure was observed in the fifth-year medical students.
      CONCLUSION: The students have an appropriate picture of the physicians' figure
      even at the beginning of their medical studies but still needs an education in
      professionalism. It seems that the fifth-year students perceive physicians as
      more self-centred when compared to their first-year colleagues.

PMID- 25568574
TI  - Exhausting multiple hemodialysis access failures.
AB  - INTRODUCTION: Vascular access is often considered the Achilles heel the of
      hemodialysis because of its impact on morbidity, all cause mortality and finally
      costs of these patients. The most common complication of permanent hemodialysis
      (HD) vascular access is thrombosis, with some cases being related to
      hypercoagulability states. Antiphospholipid antibody syndrome (APAS) is a cause
      of increased thrombotic tendency, and this may complicate the management of such
      patients on HD. CASE REPORT: We describe a 41-year-old woman with end stage renal
      disease (ESRD) from Adult Polycystic Kidney Disease who was referred to our
      tertiary care center for treatment and selection of renal replacement therapy
      form. It was thought to initiate with peritoneal dialysis considering her actual
      conditions. She was putted on hemodialysis for several sessions, and a subclavian
      cathether was her first vascular access. The surgeon created an arterio-venous
      fistula which did not mature. After the implantation of the peritoneal cathether
      she started peritoneal dialysis and continued living with that for 2 years. She
      felt exhausted and because of a grave peritonitis episode accompanied with
      procedure failure and a long hospitalization she was transferred to hemodialysis.
      Renal transplantation was not possible because she didn't have a kidney donation.
      She was maintained on regular HD, but her dialysis care was complicated by
      recurrent vascular access failures. She had multiple interventions for arterio
      venous fistulas and grafts but almost all of them failed due to thrombosis to the
      extent that only one access site was available for her routine renal replacement
      treatment. A thorough thrombophilia screen confirmed the presence of
      antiphospholipid antibodies. A diagnosis of APAS was made and she was
      anticoagulated with warfarin. The AVG made in this last available site is still
      working from 18 months. If it fails we have no answers and solutions for her.
      CONCLUSION: The presence of APAS can complicate HD management by causing
      recurrent vascular access thrombosis and failure, and nephrologist must remain
      alert to this possibility. Checking and treating as soon as possible it's our
      future challenge.

PMID- 25568576
TI  - Back Pain in Children and Diagnostic Value of (99m)Tc MDP Bone Scintigraphy.
AB  - AIM: The aim of our study is to assess the diagnostic value of Technituim-(99m)
      Methyle diphosphonate ((99m)Tc-MDP) Bone scintigraphy in the assessment of
      children with back pain. METHODS: Included in this retrospective study were 68
      child referred to us complaining of back pain (mean age of 13+ 2). There were 45
      boys and 23 girls. All children have been investigated with conventional x-ray
      which revealed normal or inconclusive result. All underwent bone scintigraphy
      after the injection of (99m)Tc-MDP with calculated doses according to there body
      weights. RESULTS: Bone scintigraphy revealed 17 (25%) abnormal scans in 11 boys
      and 6 girls. Scans findings were suggestive of spondylolysis (n=4); malignancy
      including primary tumors and metastases (n=3); infection including osteomyelitis
      and discitis (n=3); sacroiliitis (n=2); benign tumors (n=2); pseudo fractures in
      ribs (n=1); necrosis in femoral head epiphysis(n=1) and nonskeletal-renal
      retention due to hydronephrosis (n=1). Sensitivity, specificity and accuracy of
      bone scan in detecting gross skeletal abnormality as a cause for back pain were
      94% and 100% and 99% respectively. CONCLUSION: Bone isotope scan is a sensitive
      imaging modality in the assessment of pediatric patients with back pain. It is a
      reliable modality to detect and role out most benign and aggressive serious
      etiologies.

PMID- 25568578
TI  - Ultrasound measurement of cervical length as predictor of threatened preterm
      birth: a predictive model.
AB  - INTRODUCTION: The incidence of preterm delivery has been increasing even in
      developed countries and remains a serious problem for fetuses and neonates.
      Although many predictors for preterm delivery have been proposed, complete
      prediction and prevention have not yet been established. AIMS: To examine the
      potential association between sonographic measurement of cervical length and
      threatened preterm birth (TPTB) in pregnant woman at 24-36 weeks of gestation.
      MATERIALS AND METHODS: A cross-sectional study included a total of 360 pregnant
      woman at 24-36 weeks of gestation categorized in two groups: TPTB group (n=160)
      and non TPTB group (n=200). The study was carried out at the Department of
      Obstetrics and Gynecology of the Clinical Center University of Sarajevo (KCUS).
      Sociodemographic and clinical characteristics of patients were obtained from
      medical records and physical examination by gynecologist. Transvaginal sonography
      was carried out by GE Voluson 730. RESULTS: There was a significant association
      between TPTB and sonographic measurement of cervical length <25 mm (P<0.001). The
      logistic regression model was statistically significant, x(2)(7) = 281.530, P<0.
      001. The model explained 72.6% of the variance in TPTB and correctly classified
      88.1% of cases. Sensitivity was 83.8%, specificity was 91.5%, positive predictive
      value was 88.7% and negative predictive value was 87.6%. Out of the 7 predictor
      variables only 5 were statistically significant: cervical length, cervical
      consistency, rupture of membranes, uterine contractions and amine odor test.
      CONCLUSION: The findings of this study suggest association between sonographic
      measurement of cervical length and TPTB.

PMID- 25568577
TI  - Preoperative kidney tumor embolization as procedure for therapy of advanced
      kidney cancer.
AB  - INTRODUCTION: Preoperative kidney tumor embolization is standard procedure for
      therapy in advanced kidney cancer. Preoperative embolization has a goal to reduce
      intraoperative bleeding and also to shorten the time of surgery. MATERIALS AND
      METHODS: We retrospectively observed 50 patients between 2000-2011, in which the
      preoperative embolization was performed. Mean age of patients was 64 years. All
      patients with preoperative embolization were compared with the group of 51
      patients from Urology Sarajevo, who underwent nephrectomy without preoperative
      embolization. RESULTS: Symptoms that are dominating among patients were
      haematuria and pain. Analysis of mean size of tumors based on CT evaluation
      showed statistically significance in between the biggest size of tumors in group
      from Hamburg (9.11+/-3cm) and the smallest size of tumors in Sarajevo group
      (4.94+/-1.6cm) p=0.0001. Reason for this is difference in selection of patients
      for treatment in Hamburg from Sarajevo. CONCLUSION: Kidney as functional
      finishing organ is extremely suitable for transcatheter therapeutic procedures.
      The gold standard in the treatment of advanced and metastatic tumor is the
      nephrectomy. As preparation for nephrectomy in metastatic cancer total capillary
      embolization is performed. After embolization, surgery is shorter, procedure can
      be done 24-48 hours after embolization or delayed nephrectomy done 2-3 weeks
      after the intervention.

PMID- 25568579
TI  - Evaluation of Extracorporeal Shock Wave Lithotripsy (ESWL): Efficacy in Treatment
      of Urinary System Stones.
AB  - INTRODUCTION: Elimination of stone is determined by size and its localization.
      Stone from the ureter in 80% of cases can be eliminated spontaneously. If the
      stone by its characteristics is not spontaneously eliminated, taken are further
      steps and therapeutic protocols to solve this problem. MATERIAL AND METHODS: The
      study was prospective, open and comparative. It was conducted at the Urology
      Clinic Clinical Center of Sarajevo University in the period from 2007 to 2013.
      The study included 404 patients with urinary tract lithiasis treated by ESWL.
      ESWL treatment is performed on the machine Siemens Model Lithostar Multiline,
      which has a combined ultrasonographic and fluoroscopic display, large energy
      density in order to obtain optimum focus (without damaging surrounding tissue)
      and minimal pain that on rare occasions requires for mild sedation-sedation.
      RESULTS: From a total of 404 patients included in the study there were 234
      (57.92%) male and 170 (42.08%) female patients. The most common type of stone
      both in female and male patients was calcium type. From a total of 262 calcium
      stones, 105 of them (40.07%) was present in female patients and 157 (59.92%) in
      male. Share of infectious type of stone in female patients was 63 (49.60%) and 64
      among males (50.39%). Other stones were less abundant in both the gender groups
      and their total number was only 17. In women their frequency was 2 (13.33%) and
      13 among males (86.67%). There was a significant difference in the frequency of
      different types of stones by gender (x2 = 11.47, p = 0.009). CONCLUSION: There
      was no statistically significant correlation between the number of treatments and
      localization of stones in the ureter, as well as a statistically significant
      correlation between the size of the stone and the localization of calculus in the
      ureter.

PMID- 25568580
TI  - Telemetric detection of chronic obstructive pulmonary disease and investigation
      of quality of life for people working in shipbuilding industry.
AB  - INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) has a significant
      impact on quality of life-related health. AIM: It was the detection of Chronic
      Obstructive Pulmonary Disease by using telemetric methods and the investigation
      of the quality of life for people working in Shipbuilding Industry compared with
      a control group. METHODS: A group of one hundred men working in the shipbuilding
      industry aged 51.8 +/- 8.2 years old and a control group of one hundred men of
      the general population aged 51.1 +/- 6.4 years were studied. All participants
      completed the General Health Questionnaire - 28, the Fagerstrom test and a form
      with demographic characteristics. Pulmonary function test results were
      electronically sent to a specialist for evaluation. RESULTS: People working in
      the shipbuilding zone had significantly lower values (p<0.001) in FVC, FEV1 and
      FEV1/FVC compared with the general population participants. Worse social
      functionality was exhibited by workers in the shipbuilding zone, people with
      elementary education, unemployed and by those suffering from comorbidities (p
      <0.001). CONCLUSIONS: Health level and its individual dimensions are both
      associated with health self-assessment and occupational and economic status. The
      coexistence of chronic diseases and smoking dependence affects emotion and social
      functioning of individuals.

PMID- 25568581
TI  - Survey determinant factors of telemedicine strategic planning from the managers
      and experts perspective in the health department, isfahan university of medical
      sciences.
AB  - INTRODUCTION: Awareness of Outlook, objectives, benefits and impact of
      telemedicine technology that can promote services quality, reduce costs, increase
      access to Specialized and subspecialty services, and immediately guide the health
      system subconsciously to the introduction greater use of technology. Therefore,
      the aim of this study was to determine the strengths, weaknesses, opportunities
      and threats in the telemedicine strategic planning from the managers and experts
      perspective in the health department, Isfahan University of Medical Sciences, in
      order to take a step towards facilitating strategic planning and approaching the
      equity aim in health in the province. METHOD: This is a descriptive-analytical
      study, that data collection was done cross-sectional. The study population was
      composed of all managers and certified experts at the health department in
      Isfahan university of Medical Sciences. The sample size was 60 patients according
      to inclusion criteria. Information was collected by interview method. Researcher
      attempted to use the structured and specific questionnaire Then were investigated
      the viewpoints of experts and managers about determinative factors (strengths,
      weaknesses, opportunities and threats) in the strategic planning telemedicine.
      Data were analyzed using descriptive statistics (frequency, mean) and software
      SPSS 19. RESULTS: Data analysis showed that change management (100%) and
      continuity of supply of credit (79/3%) were weakness point within the
      organization and strengths of the program were, identity and health telemedicine
      programs (100%), goals and aspirations of the current directors of the
      organization and its compliance with the goals of telemedicine (100%), human
      resources interested using computers in daily activities in peripheral levels
      (93/1%). Also organization in the field of IT professionals, had opportunities,
      and repayment specialist's rights by insurance organizations is a threat for it.
      CONCLUSIONS: According to the strengths, weaknesses, opportunities and threats
      points determined by managers and experts, and compare it with success and
      failure factors, which are defined by different researchers, it seems will be
      fail to implement of telemedicine in the province at present. But according to
      the strengths identified by managers and experts, there are a lot of potential
      for telemedicine in the province, and may be used, in relation to telemedicine
      projects, with a 3 or 5 year strategic plan, and taking steps to get closer to
      the equity aim in health.

PMID- 25568582
TI  - Organizational Factors that Affect the Implementation of Information Technology:
      Perspectives of Middle Managers in Iran.
AB  - OBJECTIVE: to examine the organizational factors affecting the application of
      information technology in hospitals. Since the organizational factors are one of
      the most important determinants of successful projects, by understanding their
      impact and identifying them it can help planning a systematic IT implementation.
      METHODS: In this cross-sectional descriptive study 110 middle managers were
      chosen from teaching hospitals. Structured questionnaire was used for the data
      collection. RESULTS: There was a significant relationship between organization
      resource, organizational knowledge, process, management structure and values and
      goals with implementation of information technology. CONCLUSION: Findings showed
      that organizational factors had a considerable impact on implementation of
      information technology. Top managers must consider the important aspects of
      effective organizational factors.

PMID- 25568583
TI  - Outcome of endovenous laser ablation of varicose veins.
AB  - INTRODUCTION: In Bosnia and Herzegovina according to available data, treatment of
      incompetent superficial lower extremity varicose veins by endovenous laser
      ablation (EVLA) has been introduced two years ago and so far no paper has been
      published regarding results of EVLA treatment of patients from our country. We
      wanted to present our results with EVLA treatment. AIM OF STUDY: to evaluate and
      compare primary posttreatment outcomes of endovenous laser ablation (EVLA) with
      classical surgical method of varicose vein treatment. PATIENTS AND METHODS: The
      study was clinical and prospective. It was carried out at Clinic for vascular
      surgery in Sarajevo where fifty-eight (58) patients received surgical treatment
      for varicose veins and in Aesthetic Surgery Center "Nasa mala klinika" in
      Sarajevo were sixty-one (61) patients with varicose veins were treated by
      endovenous laser ablation. Total 119 patients (limbs) with pathologic reflux only
      in great saphenous vein were evaluated between 1st of January 2013 and 31st of
      April 2014. Following primary outcome endpoints were evaluated smean day of
      return to normal everyday activities, patient subjective quantification of pain
      during first seven days after intervention, incidence of deep venous thrombosis
      (DVT), incidence of wound bleeding requiring surgical intervention, incidence of
      peri-saphenous vein hematoma and infection rate. RESULTS: Mean of return to
      normal activities (expressed in days after intervention); EVLA vs. stripping
      (surgery) =1.21vs12.24, T test 13,619; p=0, 000, p<0,05. T test was used for
      comparing Mean value of visual pain analog scale for the first 7 days between
      groups, for all seven days pain was significantly higher in surgical group of
      patients as compared to EVLA group; p<0,05. Incidence of hematoma greater than 1%
      of total body surface area was significantly higher in patients receiving
      surgical treatment; Pearson Chi Square=23,830, p<0,05; odds ratio:10,453.
      Incidences of infection, deep venous thrombosis and posttreatment bleeding were
      not statistically different between analyzed groups; EVLA vs Surgery (Pearson Chi
      Square =3,237; p>0,05; Pearson Chi Square=2,139, p>0,05, Pearson Chi
      Square=2,139, p>0,05, respectively.). CONCLUSION: EVLA offers better patient
      recovery in terms of significantly lower post treatment pain, faster return to
      everyday activities and lower incidence of bruising (hematomas).

PMID- 25568584
TI  - Occupational overuse syndrome (technological diseases): carpal tunnel syndrome, a
      mouse shoulder, cervical pain syndrome.
AB  - Technological diseases are diseases of the modern era. Some are caused by
      occupational exposures, and are marked with direct professional relation, or the
      action of harmful effects in the workplace. Due to the increasing incidence of
      these diseases on specific workplaces which may be caused by one or more causal
      factors present in the workplace today, these diseases are considered as
      professional diseases. Severity of technological disease usually responds to the
      level and duration of exposure, and usually occurs after many years of exposure
      to harmful factor. Technological diseases occur due to excessive work at the
      computer, or excessive use of keyboards and computer mice, especially the non
      ergonomic ones. This paper deals with the diseases of the neck, shoulder, elbow
      and wrist (cervical radiculopathy, mouse shoulder and carpal tunnel syndrome), as
      is currently the most common diseases of technology in our country and abroad.
      These three diseases can be caused by long-term load and physical effort, and are
      tied to specific occupations, such as occupations associated with prolonged
      sitting, working at the computer and work related to the fixed telephone
      communication, as well as certain types of sports (tennis, golf and others). 

PMID- 25568585
TI  - A design protocol to develop radiology dashboards.
AB  - AIM: The main objective of this descriptive and development research was to
      introduce a design protocol to develop radiology dashboards. MATERIAL AND
      METHODS: The first step was to determine key performance indicators for radiology
      department. The second step was to determine required infrastructure for
      implementation of radiology dashboards. Infrastructure was extracted from both
      data and technology perspectives. The third step was to determine main features
      of the radiology dashboards. The fourth step was to determine the key criteria
      for evaluating the dashboards. In all these steps, non-probability sampling
      methods including convenience and purposive were employed and sample size
      determined based on a persuasion model. RESULTS: Results showed that there are 92
      KPIs, 10 main features for designing dashboards and 53 key criteria for
      dashboards evaluation. As well as, a Prototype of radiology management dashboards
      in four aspects including services, clients, personnel and cost-income were
      implemented and evaluated. Applying such dashboards could help managers to
      enhance performance, productivity and quality of services in radiology
      department.

PMID- 25568586
TI  - Identification of an Alternate Maxillary Apical Base Landmark from Pre-existing
      Substitutions.
AB  - BACKGROUND: Cephalometrically the position of maxilla is usually assessed by
      point A, which is one of the most common cephalometric landmarks used for spatial
      analysis of maxilla, however in certain scenarios we require a alternative
      landmark. AIMS: In this study a nearest alternative maxillary apical base
      landmark was identified for Point A substitutions given by different authors.
      METHODS AND MATERIAL: A cross sectional study was conducted on thirty (30) good
      quality lateral cephalograms. Only those lateral cephalograms were selected where
      Point A was easily identified. Landmarks: Sella (S), Nasion (N), Point A and
      three substitution points Y, L, X were traced. Angles formed by SN with Point A
      (Angle SNA) and three substitution points (Angle SNY, SNX, SNL) were measured.
      Correlation of angle SNA with angles SNY, SNX and SNL were derived. Statistical
      analysis used. RESULTS: Mean and standard deviation for Angles SNA, SNY, SNL and
      SNX were calculated individually for males and females. 'T' Test was applied to
      determine statistical significance for all the parameters i.e Age, Angles SNA,
      SNY, SNL and SNX respectively. Karl Pearson correlation coefficient was carried
      out to determine the statistical significant correlation for Angle SNA with SNY,
      SNL and SNX. RESULTS: A mean value of 82.8 degrees  +/-1.9 degrees , 83.1 degrees
      +/-1.8 degrees , 78.3 degrees  +/-2.9 degrees  and 78.7 degrees  +/-2.7 degrees 
      for Angle's SNA, SNY, SNL and SNX respectively was observed. A statistically
      significant correlation was observed between angles SNA & SNY, SNL, SNX & strong
      positive correlation was observed with angle SNY. CONCLUSIONS: We conclude that
      Point Y is the most nearing maxillary apical base landmark to Point A. Hence
      maxillary apical base landmark can be substituted by Point Y where identification
      of point A is not obvious.

PMID- 25568587
TI  - The most influential scientists in the development of the medical informatics
      (2): morris f. Collen.

PMID- 25568588
TI  - Efficiently and Effectively Evaluating Public Service Announcements: Additional
      Evidence for the Utility of Perceived Effectiveness.
AB  - Recent research has made significant progress identifying measures of the
      perceived effectiveness (PE) of persuasive messages and providing evidence of a
      causal link from PE to actual effectiveness (AE). This article provides
      additional evidence of the utility of PE through unique analysis and
      consideration of another dimension of PE important to understanding the PE-AE
      association. Current smokers (N =1,139) watched four randomly selected anti
      smoking Public Service Announcements (PSAs). PE scores aggregated by message were
      used instead of individual PE scores to create a summed total, minimizing the
      likelihood that PE perceptions are consequences of an individual's intention to
      quit, supporting instead the PE->AE order. Linear regression analyses provide
      evidence of PE's positive and significant influence on smoking cessation-related
      behavioral intentions.

PMID- 25568589
TI  - Fast and Exact Continuous Collision Detection with Bernstein Sign Classification.
AB  - We present fast algorithms to perform accurate CCD queries between triangulated
      models. Our formulation uses properties of the Bernstein basis and Bezier curves
      and reduces the problem to evaluating signs of polynomials. We present a
      geometrically exact CCD algorithm based on the exact geometric computation
      paradigm to perform reliable Boolean collision queries. Our algorithm is more
      than an order of magnitude faster than prior exact algorithms. We evaluate its
      performance for cloth and FEM simulations on CPUs and GPUs, and highlight the
      benefits.

PMID- 25568591
TI  - Technology addiction's contribution to mental wellbeing: The positive effect of
      online social capital.
AB  - This research examines the effect of online social capital and Internet use on
      the normally negative effects of technology addiction, especially for individuals
      prone to self-concealment. Self-concealment is a personality trait that describes
      individuals who are more likely to withhold personal and private information,
      inhibiting catharsis and wellbeing. Addiction, in any context, is also typically
      associated with negative outcomes. However, we investigate the hypothesis that
      communication technology addiction may positively affect wellbeing for self
      concealing individuals when online interaction is positive, builds relationships,
      or fosters a sense of community. Within these parameters, increased communication
      through mediated channels (and even addiction) may reverse the otherwise negative
      effects of self-concealment on wellbeing. Overall, the proposed model offers
      qualified support for the continued analysis of mediated communication as a
      potential source for improving the wellbeing for particular individuals. This
      study is important because we know that healthy communication in relationships,
      including disclosure, is important to wellbeing. This study recognizes that not
      all people are comfortable communicating in face-to-face settings. Our findings
      offer evidence that the presence of computers in human behaviors (e.g., mediated
      channels of communication and NCTs) enables some individuals to communicate and
      fos ter beneficial interpersonal relationships, and improve their wellbeing.

PMID- 25568590
TI  - Walking Ability and Its Relationship to Self-Rated Health in Later Life.
AB  - This study investigated the relationship between self-assessed overall health
      (SRH) and walking ability among older adults (n = 239) gauged using three well
      established measures of walking ability ("normal" and "fast" walking speeds, and
      perceived walking difficulty). Logistic regression models adjusted for health,
      behavioral, and sociodemographic variables were used to estimate the relationship
      between the three measures of walking ability and SRH. Walking ability was
      significantly associated with SRH; notably, only normal walking speed
      discriminated between participants in all three SRH comparisons (good versus
      poor/bad, good versus fair, or excellent versus good). Health care providers,
      family, and friends should be attentive to reduced walking speed or complaints
      about difficulty walking because these are harbingers of health decline.

PMID- 25568592
TI  - Mindfulness Meditation Training and Self-Referential Processing in Social Anxiety
      Disorder: Behavioral and Neural Effects.
AB  - This study examined the effects of mindfulness-based stress reduction (MBSR) on
      the brain-behavior mechanisms of self-referential processing in patients with
      social anxiety disorder (SAD). Sixteen patients underwent functional magnetic
      resonance imaging while encoding self-referential, valence, and orthographic
      features of social trait adjectives. Post-MBSR, 14 patients completed
      neuroimaging. Compared to baseline, MBSR completers showed (a) increased self
      esteem and decreased anxiety, (b) increased positive and decreased negative self
      endorsement, (c) increased activity in a brain network related to attention
      regulation, and (d) reduced activity in brain systems implicated in conceptual
      linguistic self-view. MBSR-related changes in maladaptive or distorted social
      self-view in adults diagnosed with SAD may be related to modulation of conceptual
      self-processing and attention regulation. Self-referential processing may serve
      as a functional biobehavioral target to measure the effects of mindfulness
      training.

PMID- 25568593
TI  - The Vietnam Multicomponent Collaborative Care for Depression Program: Development
      of Depression Care for Low- and Middle-Income Nations.
AB  - In this article, we discuss the Vietnam Multicomponent Collaborative Care for
      Depression Program, which was designed to provide evidence-based depression care
      services in low-resource, non-Western settings such as Vietnam. The article
      provides the program development background; the social, economic, and political
      context in which the program was developed; and the structure and content of the
      program and their underlying rationale in the context of rural Vietnam. Although
      the program was found to be acceptable, feasible, and effective in reducing
      depression outcomes, we did face challenges in implementation, which are outlined
      in this article. Key challenges included cultural factors (e.g., a lack of
      recognition of depression as a health-related entity amenable to professional
      treatment, relatively low levels of psychological mindedness useful for
      understanding of psychological interventions) and health system (e.g., lack of
      mental health specialists, overburdened health providers unfamiliar with
      behavioral interventions) factors. We discuss the strategies we employed to
      resolve these challenges and our successes and failures therein. We conclude with
      recommendations for others interested in implementing similar programs in low-
      and middle-income countries settings.

PMID- 25568594
TI  - A study of unusual pacemaker infection by mycobacterium tuberculosis in Indian
      patients.
AB  - BACKGROUND: The expanding clinical indications of cardiac rhythm management have
      led to an increased use of pacemaker implantation which is associated with
      increased incidence of pacemaker infections. Staphylococcus aureus and
      epidermidis account for the vast majority of pacemaker infections. Pacemaker
      infection due to Mycobacterium tuberculosis (M. tuberculosis) is very rare, only
      few cases having been reported till date. METHODS: We describe here a study of
      three patients of pacemaker pocket infection with M. tuberculosis. CONCLUSION:
      The possibility of mycobacterial pacemaker infection should always be kept in
      mind in patients with delayed pacemaker infection.

PMID- 25568595
TI  - Need for gender neutral policy at workplace.

PMID- 25568597
TI  - Common musculoskeletal problem experienced by fishing industry workers.
AB  - INTRODUCTION: Work-related musculoskeletal disorders (WMSDs) are a common health
      problem throughout the world and a major cause of disability in the workplace.
      Awkward working posture is a main risk factor for developing WMSDs. Assessment of
      exposure level to WMSDs risks can be an appropriate base for planning and
      implementing interventional ergonomics program in the workplace. Fihing in India
      is a major industry in the coastal states employing over 14 million people. The
      job demand of fishermen make them vulnerable for various musculoskeletal problems
      This study was conducted among workers of fishing industry in Mumbai, India with
      the objective to determine WMSDs prevalence in fishing industry. MATERIALS AND
      METHODS: In this cross-sectional study, 110 randomly selected workers from
      fishing industry, India, Mumbai, Anonymous questionnaire was used to study
      prevalence of WMSDs.visual analogue scale used to assess intensity of pain.
      RESULTS: The results of NMQ revealed that WMSDs occurrence was high. The highest
      rates of WMSDs prevalence were reported in Low back(92.4%), Shoulder (64.8%) and
      Knee(31%) and Hand (25%). CONCLUSION: This study showed that maximum of the
      fishermen have musculoskeletal problem with the most common joint involved is low
      back and then followed by shoulder, knee, and hand. Ergonomic risk factor
      involved were found to be repeated pulling and throwing of the net as well as
      repeated bending forward action to lift heavy load and transfer that heavy load.

PMID- 25568598
TI  - Occupational stress among staff nurses: Controlling the risk to health.
AB  - INTRODUCTION: Nursing has been identified as an occupation that has high levels
      of stress. Job stress brought about hazardous impacts not only on nurses' health
      but also on their abilities to cope with job demands. OBJECTIVES: This study
      aimed at finding out the degree of work-related stress among the staff nurses and
      various determinants, which have a impact on it. MATERIALS AND METHODS:
      Institutional-based cross-sectional study conducted on GNM qualified nurses.
      Predesigned and pre-tested questionnaire covering their sociodemographic
      variables in part I and professional life stress scale by David Fontana in part
      II. Analysis used was Chi-square test and logistic regression for various
      factors. RESULTS: Risk for professional stress due to poor and satisfactory
      doctor's attitude was found about 3 and 4 times more than with excellent attitude
      of doctors toward the staff nurses. A statistically significant association (P <
      0.024) between department of posting and level of stress. Nurses reported that
      they had no time for rest, of whom 42% were suffering from moderate-to-severe
      stress. The nurses who felt that the job was not tiring were found to be less
      stressed as those who perceived job as tiring (OR = 0.43). CONCLUSION: The main
      nurses' occupational stressors were poor doctor's attitude, posting in busy
      departments (emergency/ICU), inadequate pay, too much work, and so on. Thus,
      hospital managers should initiate strategies to reduce the amount of occupational
      stress and should provide more support to the nurses to deal with the stress.

PMID- 25568599
TI  - Respiratory response to tobacco dust exposure among biddi binders: A follow up
      and bronchodilator study.
AB  - INTORDUCTION: The tobacco dusts get air borne during biddi making and it is
      inhaled by the biddi binders, which affects their health. RESULTS: In a follow-up
      study, 86 biddi binders (male, 41; female, 45) were studied at a gap of 2 years.
      A high respiratory morbidity was observed among males than females both in the
      initial and follow-up study. The main complaints such as cough, sputum, and
      breathlessness showed high prevalence rates in the follow-up study. The high
      prevalence rates of weakness, giddiness, chronic diarrhea, and dyspepsia were
      noted in most of the cases the above complaints showed higher rates in the follow
      up study. Pulmonary function test (PFT) values in the follow-up study of male and
      female biddi binders showed lowered compared with the initial study of same
      gender. In male and female biddi binders, the lung volumes SVC, FVC, FEV1, and
      the flow rates FEF0.2-1.2 l, FEF25%-75%, FEF75%-85% were significantly lowered in
      the follow-up study compared with the initial study. Age-related decrement in PFT
      was observed in both the studies. In nonsmokers, smokers, and ex-smokers, the PFT
      values are lowered. The current smokers have the lowest values in both the
      studies. With the administration of the bronchodilator aerosol (salbutamol) in 63
      biddi binders (male, 27; female, 36), the effect of bronchodilator aerosol on the
      PFT parameters showed significant changes as all PFT parameters showed positive
      bronchodilatation. CONCLUSION: The pattern of bronchodilator response on PFT
      values of the biddi binders suggests that the obstructions in the airways are
      reversible in nature.

PMID- 25568600
TI  - A study on occupational asthma among workers of silk filatures in South India.
AB  - BACKGROUND: The production of silk is a multidimensional and multistep process
      involving exposure of workers to allergens at work place. The silk allergen has
      been implicated in the development of bronchial asthma. OBJECTIVES: To identify
      the prevalence of occupational asthma (OA) and to identify sensitization to silk
      allergen and among workers in silk filature units. MATERIALS AND METHODS: A
      community-based cross-sectional study was conducted in silk filature units of
      Ramanagara (Silk City) in Karnataka, South India, for a period of 6 months. One
      hundred and twenty workers of silk filature units who met the inclusion and
      exclusion criteria were recruited into the study group. For comparison, a control
      group comprising of 120 individuals not working in silk filature units was
      constituted. All the subjects were interviewed using the standardized
      International Union against Tuberculosis and Lung Diseases (IUATLD) Questionnaire
      and subjected to the skin prick test, which used the extracts of silk allergen.
      RESULTS: The study group comprised of 35 males and 85 females, whereas the
      control group comprised of 58 males and 62 females. The prevalence of
      occupational asthma among workers in silk filatures was 20.83%. It was observed
      that 35.83% of those in the study group and 20.83% of those in the control group
      were found to be sensitive to silk allergen. This difference was statistically
      significant (chi(2)= 6.64; P < 0.05). CONCLUSION: There is a high burden of
      sensitization to silk allergen and occupational asthma among silk filature
      workers in South India.

PMID- 25568596
TI  - Sleep apnea and occupational accidents: Are oral appliances the solution?
AB  - BACKGROUND: Dental practitioners have a key role in the quality of life and
      prevention of occupational accidents of workers with Obstructive Sleep Apnea
      Syndrome (OSAS). AIM: The aim of this study was to review the impact of OSAS, the
      Continuous Positive Airway Pressure (CPAP) therapy, and the evidence regarding
      the use of oral appliances (OA) on the health and safety of workers. MATERIALS
      AND METHODS: Searches were conducted in MEDLINE (PubMed), Lilacs and Sci ELO.
      Articles published from January 1980 to June 2014 were included. RESULTS: The
      research retrieved 2188 articles and 99 met the inclusion criteria. An increase
      in occupational accidents due to reduced vigilance and attention in snorers and
      patients with OSAS was observed. Such involvements were related to excessive
      daytime sleepiness and neurocognitive function impairments. The use of OA are
      less effective when compared with CPAP, but the results related to excessive
      sleepiness and cognitive performance showed improvements similar to CPAP.
      Treatments with OA showed greater patient compliance than the CPAP therapy.
      CONCLUSION: OSAS is a prevalent disorder among workers, leads to increased risk
      of occupational accidents, and has a significant impact on the economy. The CPAP
      therapy reduces the risk of occupational accidents. The OA can improve the work
      performance; but there is no scientific evidence associating its use with
      occupational accidents reduction. Future research should focus on determining the
      cost-effectiveness of OA as well as its influence and efficacy in preventing
      occupational accidents.

PMID- 25568601
TI  - A study of certain correlates of job satisfaction among judicial personnel, in a
      district of Western Maharashtra.
AB  - BACKGROUND: In present scenario, the legal profession has gained utmost
      importance, which makes the job of a lawyer the most challenging, with lots of
      mental and physical strain. The rewards can be great, but so are the pressures.
      High job demands lead to imbalance between what is expected and what is received
      (job dissatisfaction) which, in turn, leads to job strains. So, the present study
      focused on the impact of certain variables on job satisfaction of the
      judiciaries. OBJECTIVES: To study the level of job satisfaction among judicial
      personnel; to identify the impact of job level (hierarchy) in the experience of
      job satisfaction; to find the gender difference (if any) for the level of job
      satisfaction; and to examine the pattern of relationship of certain variables
      with job satisfaction. MATERIALS AND METHODS: A cross-sectional study was
      conducted in 1 year duration, in total 965 judicial personnel of different courts
      in the district of Sangli, which involved data collection using predesigned
      proforma. A scale, having 15 different independent predictors was used as a
      validated screening tool, to calculate their job satisfaction score. The most
      contributing variable and its correlation with job satisfaction was found by
      stepwise multiple regression and correlation analysis using SPSS Version-16.
      RESULTS AND CONCLUSION: Out of the total, Class I judiciaries were 692 (71.7%). A
      majority (71.4%) of the study subjects were male. Overall mean job satisfaction
      score was 5.38 +/- 2.7. Twenty-three percent females, compared with only 9%
      males, had low job satisfaction (P < 0.5). The best predictor of job satisfaction
      in males and females was emotional exhaustion (beta = 0.191) and conflicts
      between values and practice (beta = 0.252), respectively. Higher is the job
      satisfaction score, lesser the level of job satisfaction. The findings of the
      study revealed that job satisfaction was found to be significantly (P < 0.0005)
      and positively correlated with all the variables in the study.

PMID- 25568602
TI  - Work-related musculoskeletal disorders among health care professionals: A cross
      sectional assessment of risk factors in a tertiary hospital, India.
AB  - BACKGROUND: Work-related musculoskeletal disorders (WMSDs) are responsible for
      morbidity in many working populations. Apart from lowering the quality of
      workers' life and reducing the productivity, WMSDs are the most expensive form of
      work disability, attributing to about 40% of all costs toward the treatment of
      work-related injuries. WMSDs are considered to be multifactorials that are caused
      due to the interactions between various risk factors, which result in conditions
      that vary across different occupations. Although health care profession is known
      to be at a high risk for WMSDs, it is one of the least-studied occupations. Most
      of the previous studies on WMSDs among health care workers were limited to any
      one of the professional groups such as nurses, physical therapists, dentists, and
      others. Hence this study was aimed at looking into the WMSDs affecting five
      different health care professionals working in a tertiary care hospital. It
      compared the prevalence and distribution of WMSDs among the five groups,
      evaluated the multiple risk factors that contribute to the development of WMSDs,
      and identified the high-risk group. MATERIALS AND METHODS: It was a cross
      sectional study conducted among dentists, laboratory technicians, nurses,
      physicians, and physiotherapists of various clinical departments in a tertiary
      care hospital in Chennai, India, from January to June 2013. Face-to-face
      interviews as well as observational analysis of various tasks were employed.
      Different combinations of validated and standardized questionnaires were used for
      collecting different types of data. RESULTS: A high proportion of health care
      professionals reported WMSDs at one or the other body region, lower back being
      the most commonly affected area. Working in the same position for long periods,
      working in awkward or cramped positions and handling an excessive number of
      patients or samples in one day were found to be the most commonly reported job
      risk factor that contributed to the development of WMSDs, in this study.
      CONCLUSION: Among all the health care professionals assessed in this study,
      nurses were found to be at the highest risk, whereas physicians were at the
      lowest risk. A longitudinal study using quantitative analytical tools may give a
      more accurate estimate of WMSDs and job risk factors, which would pave way for
      making more precise recommendations to eliminate the risk factors and thereby
      prevent WMSDs.

PMID- 25568603
TI  - Global mesothelioma epidemic: Trend and features.
AB  - BACKGROUND: Mesothelioma incidence has taken epidemic proportions in various
      countries. The trend of the epidemic remains undefined. OBJECTIVE: To collect the
      most recent available data on mesothelioma incidence in order to determine the
      present trend of the epidemic. MATERIALS AND METHODS: Data of the Cancer and
      Mesothelioma Registries have been reviewed. In addition, numerous researchers
      were contacted to obtain supplementary information. RESULTS: The highest
      incidence rates are reported from some countries in Europe (United Kingdom, The
      Netherlands, Malta, Belgium), and in Oceania (Australia, New Zealand). Relatively
      low incidence/mortality rates are reported from Japan and from Central Europe. In
      many countries a trend to increase continues to be observed. Data are not
      available for the mostly populous countries. CONCLUSION: Mesothelioma epidemic
      does not show signs of attenuation. The lack of data for a large majority of the
      world does not allow that the consciousness of the risks related to asbestos
      exposure is reached.

PMID- 25568604
TI  - Health profile of workers in a ship building and repair industry.
AB  - BACKGROUND: The modern ship building industry, which encompasses the ship yards
      and marine equipment manufacturing, is an important and strategic industry. The
      various activities in modern ship building, maintenance, and repair have to be
      carried out at heights, or in closed confined spaces along with the added risk of
      exposure to chemicals and metal fumes. These activities expose the workers to
      various health hazards. AIMS: This study was carried out with an aim to assess
      the health profile of workers in the ship building industry and to assess the
      occupational health issues related to ship building. SETTINGS AND DESIGN: It was
      a cross-sectional study carried out on 100 randomly selected workers in a ship
      building yard in Mumbai, and their health profile was studied. MATERIALS AND
      METHODS: The workers were enquired for history of co-morbidities, addictions and
      personal protective equipment use, health-related complaints, and were examined
      systemically as well as for bedside tests for hearing and detailed systemic
      examination as per the history or co-morbidity. RESULTS: The important
      observations were those of prevalence of addictions (69%), irregular use of
      personal protective equipments (PPEs) among 50% of paint workers, presence of
      hypertension (20%), overweight (53%), osteoarthritis (10%), hearing loss (25%),
      and poor self-care. CONCLUSIONS: Health education to the workers regarding
      occupational hazards and lifestyle diseases along with more emphasis on the use
      of PPEs with regular health examination needs reinforcement.

PMID- 25568605
TI  - Occupational inhalation of aniline fumes induced methemoglobinemea and hemolytic
      anemia precipitated days later.
AB  - Methylene blue is utilized as the main treatment of methemoglobinemia. Here we
      report two cases, in which patient suffered from aniline-induced
      methemoglobinemia with initial good response but later developed haemolytic
      anemia due to methylene blue therapy. He was treated with hydration, high flow
      oxygen and steroid therapy. Caution should be exercised while using methylene
      blue as antidote of acute methemoglobinemia as both methemoglobinemia and its
      antidote methylene blue can itself precipitate fatal haemolytic anemia. 

PMID- 25568606
TI  - Benzene, cytochrome, carcinogenesis: A topic in preventive toxicology.
AB  - Benzene is a common chemical substance with confirmed toxicity to human beings.
      The benzene toxicity can be in either acute or chronic. Also, the carcinogenicity
      of benzene is confirmed. Hence, the control of benzene usage is a topic in
      preventive toxicology; however, this substance is still problematic in many
      industrialized settings. In this article, the author discusses benzene and
      cytochrome focusing on the carcinogenesis process. A further extrapolation on the
      aspects on preventive toxicology is also included. 

PMID- 25568607
TI  - Application of principles of ergonomics in medicine.

PMID- 25568608
TI  - Serious health concerns about the electronic (e)-cigarettes.

PMID- 25568609
TI  - Clarification on Understanding epidemiological correlates: A comment on study the
      epidemiological profile of taxi drivers in the background of occupational
      environment, stress, and personality characteristics.

PMID- 25568611
TI  - Lost in Translation? A Comparison of Cancer-Genetics Reporting in the Press
      Release and its Subsequent Coverage in Lay Press.
AB  - Understanding how genetic science is communicated to the lay public is of great
      import, given that media coverage of genetics is increasing exponentially and
      that the ways in which discoveries are presented in the news can have significant
      effects on a variety of health outcomes. To address this issue, this study
      examines the presentation of genetic research relating to cancer outcomes and
      behaviors (i.e., prostate cancer, breast cancer, colon cancer, smoking and
      obesity) in both the press release (N = 23) and its subsequent news coverage (N =
      71) by using both quantitative content analysis and qualitative textual analysis.
      In contrast to earlier studies reporting that news stories often misrepresent
      genetics by presenting biologically deterministic and simplified portrayals
      (e.g., Mountcastle-Shah et al., 2003; Ten Eych & Williment, 2003), our data shows
      no clear trends in the direction of distortion toward deterministic claims in
      news articles. Also, other errors commonly attributed to science journalism, such
      as lack of qualifying details and use of oversimplified language (e.g., "fat
      gene") are observed in press releases. These findings suggest that the
      intermediary press release rather than news coverage may serve as a source of
      distortion in the dissemination of science to the lay public. The implications of
      this study for future research in this area are discussed.

PMID- 25568610
TI  - EFFECT OF TYPE 2 DIABETES MELLITUS ON BRAIN METABOLITES BY USING PROTON MAGNETIC
      RESONANCE SPECTROSCOPY-A SYSTEMATIC REVIEW.
AB  - Cerebral metabolism will be affected in T2DM either by chronic hyperglycemia or
      by chronic hypoxia. Proton magnetic resonance spectroscopy (1H-MRS) of the brain
      provides detailed information about the structure, dynamics, reaction state and
      chemical environment of molecules. It also measures the levels of brain
      metabolites such as myo-inositol (mI), N acetyl aspartate (NAA), creatine (Cr),
      choline (Cho), glutamate (Glu), glutamine (Gln) and gamma amino butyric acid
      (GABA). Several studies suggest that people with type 2 diabetes mellitus (T2DM)
      are at an increased risk of cognitive impairment in comparison with the general
      population. The altered metabolites may cause cognitive dysfunction in T2DM. This
      review article concludes that in T2DM, metabolite levels were altered in
      different regions of brain.

PMID- 25568612
TI  - Context, Challenges, and Tensions in Global Efforts to Engage Men in the
      Prevention of Violence against Women: An Ecological Analysis.
AB  - As gender-based violence prevention programs around the world increasingly
      include efforts to engage men and boys as antiviolence allies, both the profound
      benefits and the inherent complexities of these efforts are emerging.
      Acknowledging and exploring tensions associated with engaging men is an important
      element of thoughtfully fostering men's antiviolence ally movements so as to both
      respectfully invite men into anti-violence work and create effective, gender
      equitable prevention programming. To this end, this study presents descriptive
      findings regarding challenges associated with men's engagement programming from
      in-depth interviews with twenty-nine representatives of organizations that engage
      men and boys in preventing violence against women and girls in Africa, Asia,
      Europe, Oceania, and North and South America. Programs reported negotiating
      complex issues related to gender, the intersectional nature of men's identities,
      and establishing legitimacy and sustainability within communities while
      maintaining ideological focus and consistency. Additionally, programs reported
      that these tensions manifest across ecological layers of analysis, and impact
      both the participation of individual men and the programs' experiences in
      community and national contexts.

PMID- 25568613
TI  - Epidemiology of diabetes.
AB  - The disease burden related to diabetes is high and rising in every country,
      fuelled by the global rise in the prevalence of obesity and unhealthy lifestyles.
      The latest estimates show a global prevalence of 382 million people with diabetes
      in 2013, expected to rise to 592 million by 2035. The aetiological classification
      of diabetes has now been widely accepted. Type 1 and type 2 diabetes are the two
      main types, with type 2 diabetes accounting for the majority (>85%) of total
      diabetes prevalence. Both forms of diabetes can lead to multisystem complications
      of microvascular endpoints, including retinopathy, nephropathy and neuropathy,
      and macrovascular endpoints including ischaemic heart disease, stroke and
      peripheral vascular disease. The premature morbidity, mortality, reduced life
      expectancy and financial and other costs of diabetes make it an important public
      health condition.

PMID- 25568614
TI  - On integrable conservation laws.
AB  - We study normal forms of scalar integrable dispersive (not necessarily
      Hamiltonian) conservation laws, via the Dubrovin-Zhang perturbative scheme. Our
      computations support the conjecture that such normal forms are parametrized by
      infinitely many arbitrary functions that can be identified with the coefficients
      of the quasi-linear part of the equation. Moreover, in general, we conjecture
      that two scalar integrable evolutionary partial differential equations having the
      same quasi-linear part are Miura equivalent. This conjecture is also consistent
      with the tensorial behaviour of these coefficients under general Miura
      transformations.

PMID- 25568615
TI  - Tropical atmospheric circulations with humidity effects.
AB  - The main objective of this article is to study the effect of the moisture on the
      planetary scale atmospheric circulation over the tropics. The modelling we adopt
      is the Boussinesq equations coupled with a diffusive equation of humidity, and
      the humidity-dependent heat source is modelled by a linear approximation of the
      humidity. The rigorous mathematical analysis is carried out using the dynamic
      transition theory. In particular, we obtain mixed transitions, also known as
      random transitions, as described in Ma & Wang (2010 Discrete Contin. Dyn.
      Syst.26, 1399-1417. (doi:10.3934/dcds.2010.26.1399); 2011 Adv. Atmos. Sci.28, 612
      622. (doi:10.1007/s00376-010-9089-0)). The analysis also indicates the need to
      include turbulent friction terms in the model to obtain correct convection scales
      for the large-scale tropical atmospheric circulations, leading in particular to
      the right critical temperature gradient and the length scale for the Walker
      circulation. In short, the analysis shows that the effect of moisture lowers the
      magnitude of the critical thermal Rayleigh number and does not change the
      essential characteristics of dynamical behaviour of the system.

PMID- 25568616
TI  - Rayleigh-Bloch waves along elastic diffraction gratings.
AB  - Rayleigh-Bloch (RB) waves in elasticity, in contrast to those in scalar wave
      systems, appear to have had little attention. Despite the importance of RB waves
      in applications, their connections to trapped modes and the ubiquitous nature of
      diffraction gratings, there has been no investigation of whether such waves occur
      within elastic diffraction gratings for the in-plane vector elastic system. We
      identify boundary conditions that support such waves and numerical simulations
      confirm their presence. An asymptotic technique is also developed to generate
      effective medium homogenized equations for the grating that allows us to replace
      the detailed microstructure by a continuum representation. Further numerical
      simulations confirm that the asymptotic scheme captures the essential features of
      these waves.

PMID- 25568617
TI  - The rheology of three-phase suspensions at low bubble capillary number.
AB  - We develop a model for the rheology of a three-phase suspension of bubbles and
      particles in a Newtonian liquid undergoing steady flow. We adopt an 'effective
      medium' approach in which the bubbly liquid is treated as a continuous medium
      which suspends the particles. The resulting three-phase model combines separate
      two-phase models for bubble suspension rheology and particle suspension rheology,
      which are taken from the literature. The model is validated against new
      experimental data for three-phase suspensions of bubbles and spherical particles,
      collected in the low bubble capillary number regime. Good agreement is found
      across the experimental range of particle volume fraction ([Formula: see text])
      and bubble volume fraction ([Formula: see text]). Consistent with model
      predictions, experimental results demonstrate that adding bubbles to a dilute
      particle suspension at low capillarity increases its viscosity, while adding
      bubbles to a concentrated particle suspension decreases its viscosity. The model
      accounts for particle anisometry and is easily extended to account for variable
      capillarity, but has not been experimentally validated for these cases.

PMID- 25568618
TI  - Continuous analogues of matrix factorizations.
AB  - Analogues of singular value decomposition (SVD), QR, LU and Cholesky
      factorizations are presented for problems in which the usual discrete matrix is
      replaced by a 'quasimatrix', continuous in one dimension, or a 'cmatrix',
      continuous in both dimensions. Two challenges arise: the generalization of the
      notions of triangular structure and row and column pivoting to continuous
      variables (required in all cases except the SVD, and far from obvious), and the
      convergence of the infinite series that define the cmatrix factorizations. Our
      generalizations of triangularity and pivoting are based on a new notion of a
      'triangular quasimatrix'. Concerning convergence of the series, we prove theorems
      asserting convergence provided the functions involved are sufficiently smooth.

PMID- 25568619
TI  - Out-of-unison resonance in weakly nonlinear coupled oscillators.
AB  - Resonance is an important phenomenon in vibrating systems and, in systems of
      nonlinear coupled oscillators, resonant interactions can occur between
      constituent parts of the system. In this paper, out-of-unison resonance is
      defined as a solution in which components of the response are 90 degrees  out-of
      phase, in contrast to the in-unison responses that are normally considered. A
      well-known physical example of this is whirling, which can occur in a taut cable.
      Here, we use a normal form technique to obtain time-independent functions known
      as backbone curves. Considering a model of a cable, this approach is used to
      identify out-of-unison resonance and it is demonstrated that this corresponds to
      whirling. We then show how out-of-unison resonance can occur in other two degree
      of-freedom nonlinear oscillators. Specifically, an in-line oscillator consisting
      of two masses connected by nonlinear springs-a type of system where out-of-unison
      resonance has not previously been identified-is shown to have specific parameter
      regions where out-of-unison resonance can occur. Finally, we demonstrate how the
      backbone curve analysis can be used to predict the responses of forced systems.

PMID- 25568620
TI  - Towards a quantitative understanding of period-doubling wrinkling patterns
      occurring in film/substrate bilayer systems.
AB  - Compression of a stiff film on a soft substrate may lead to surface wrinkling
      when the compressive strain reaches a critical value. Further compression may
      cause a wrinkling-folding transition, and the sinusoidal wrinkling mode can then
      give way to a period-doubling bifurcation. The onset of the primary bifurcation
      has been well understood, but a quantitative understanding of the secondary
      bifurcation remains elusive. Our theoretical analysis of the branching of surface
      patterns reveals that the wrinkling-folding transition depends on the wrinkling
      strain and the prestrain in the substrate. A characteristic strain in the
      substrate is adopted to determine the correlation among the critical strain of
      the period-doubling mode, the wrinkling strain and the prestrain in an explicit
      form. A careful examination of the total potential energy of the system reveals
      that beyond the critical strain of period-doubling, the sinusoidal wrinkling mode
      has a higher potential energy in comparison with the period-doubling mode. The
      critical strain of the period-doubling mode strongly depends on the deformation
      state of the hyperelastic solid, indicating that the nonlinear deformation
      behaviour of the substrate plays a key role here. The results reported here on
      the one hand provide a quantitative understanding of the wrinkling-folding
      transition observed in natural and synthetic material systems and on the other
      hand pave the way to control the wrinkling mode transition by regulating the
      strain state in the substrate.

PMID- 25568621
TI  - Intrinsic multi-scale analysis: a multi-variate empirical mode decomposition
      framework.
AB  - A novel multi-scale approach for quantifying both inter- and intra-component
      dependence of a complex system is introduced. This is achieved using empirical
      mode decomposition (EMD), which, unlike conventional scale-estimation methods,
      obtains a set of scales reflecting the underlying oscillations at the intrinsic
      scale level. This enables the data-driven operation of several standard data
      association measures (intrinsic correlation, intrinsic sample entropy (SE),
      intrinsic phase synchrony) and, at the same time, preserves the physical meaning
      of the analysis. The utility of multi-variate extensions of EMD is highlighted,
      both in terms of robust scale alignment between system components, a pre
      requisite for inter-component measures, and in the estimation of feature
      relevance. We also illuminate that the properties of EMD scales can be used to
      decouple amplitude and phase information, a necessary step in order to accurately
      quantify signal dynamics through correlation and SE analysis which are otherwise
      not possible. Finally, the proposed multi-scale framework is applied to detect
      directionality, and higher order features such as coupling and regularity, in
      both synthetic and biological systems.

PMID- 25568622
TI  - The speed of an inclined ruck.
AB  - Steady rucks in an elastic beam can roll at constant speed down an inclined
      plane. We examine the dynamics of these travelling-wave structures and argue that
      their speed can be dictated by a combination of the physical conditions arising
      in the vicinity of the 'contact points' where the beam is peeled off the
      underlying plane and stuck back down. We provide three detailed models for the
      contact dynamics: viscoelastic fracture, a thermodynamic model for bond formation
      and detachment and adhesion mediated by a thin liquid film. The results are
      compared with experiments.

PMID- 25568623
TI  - Moving Beyond 'Aging In Place' to Understand Migration and Aging: Place Making
      and the Centrality Of Occupation.
AB  - 'Aging in place' has become a key conceptual framework for understanding and
      addressing place within the aging process. However, aging in place has been
      critiqued for not sufficiently providing tools to understand relations or
      transactions between aging and place, and for not matching the diversity of
      contemporary society in which people are moving between and across nations more
      than ever before. In this article, the authors draw from concepts of place and
      migration that are becoming increasingly visible in occupational science. The
      concept of 'aging in place' is critically examined as an example of an ideal
      where the understanding of place is insufficiently dynamic in a context of
      migration. The authors suggest that the concept of place making can instead be a
      useful tool to understand how occupation can be drawn upon to negotiate
      relationships that connect people to different places around the world, how the
      negotiated relations are embedded within the occupations that fill daily lives,
      and how this process is contextualized and enacted in relation to resources and
      capabilities.

PMID- 25568624
TI  - Influence of Prognostic Factors on OverallSurvival in Myelodysplastic Syndromes.
AB  - BACKGROUND: Accurate prediction of a patient's prognosis is useful to define the
      risk posed by the disease. Age, gender, peripheral blood cytopenia, proportion of
      bone marrow (BM) blasts, performance status, comorbidities, transfusion
      dependence, specific karyotype abnormalities and molecular biomarkers can refine
      the prediction of prognosis in MDS. AIM: to assess the influence of the some
      prognostic factors like age, gender, cytopenia, BM blast percentage, transfusion
      dependence, ferritin, hemoglobin (Hb), lactate dehydrogenase (LDH), albumin and
      specific karyotype abnormalities in myelodysplastic syndromes on overall survival
      (OS). PATIENTS AND METHODS: we retrospectively analyzed the cohort of 108
      patients diagnosed between 1.1.2011 and 31.12.2013 at the University Clinic of
      Hematology, Ss Cyril and Methodius University, Skopje, Macedonia. They were
      evaluated for clinical and hematologic features at diagnosis and at leukemic
      transformation. RESULTS: in the study group 62 were man and 46 women. Male to
      female ratio was 1.35 to 1. The differences in OS between men and women were
      significant (p = .03015). The mean age at diagnosis was 66,6 years. According to
      the age OS was 16,4 months. FAB subtypes influenced OS significantly (p =
      .03015). OS inversely correlated with BM blast percentage (p= .02327). Cytopenia
      had no impact on OS (p=.33755). Hb as a whole and groups with different levels of
      Hb had no influence on OS (p = .12142) and (p= .07535), respectively. The group
      with ferritin <500 ug/L had better OS (p=.04720). Transfusion dependence, LDH and
      albumin had no impact on OS. Leukemic transformation was noticed in 10 (9,3%)
      patients. Mortality was 36,1%. CONCLUSION: gender, FAB subtypes, BM blast
      percentage and the serum levels of ferritin had an influence on OS, while age,
      hemoglobin level, transfusion dependence, LDH and albumin had no impact on OS.

PMID- 25568625
TI  - Characteristics of calculi in the urinary tract.
AB  - INTRODUCTION: Elimination of stone is determined by size and its localization.
      Stone from the ureter in 80% of cases can be eliminated spontaneously. If the
      stone by its characteristics is not spontaneously eliminated, taken are further
      steps and therapeutic protocols to solve this problem. MATERIAL AND METHODS: The
      study was prospective, open and comparative. It was conducted at the Urology
      Clinic Clinical Center of Sarajevo University in the period from 2007 to 2013.
      The study included 404 patients with urinary tract lithiasis treated by ESWL.
      ESWL treatment is performed on the machine Siemens Model Lithostar Multiline,
      which has a combined ultrasonographic and fluoroscopic display, large energy
      density in order to obtain optimum focus (without damaging surrounding tissue)
      and minimal pain that on rare occasions requires for mild sedation-sedation.
      RESULTS: From a total of 404 patients included in the study there were 234
      (57.92%) male and 170 (42.08%) female patients. The most common type of stone
      both in female and male patients was calcium type. From a total of 262 calcium
      stones, 105 of them (40.07%) was present in female patients and 157 (59.92%) in
      male. Share of infectious type of stone in female patients was 63 (49.60%) and 64
      among males (50.39%). Other stones were less abundant in both the gender groups
      and their total number was only 17. In women their frequency was 2 (13.33%) and
      13 among males (86.67%). There was a significant difference in the frequency of
      different types of stones by gender (chi2 = 11.47, p = 0.009). CONCLUSION: There
      was no statistically significant correlation between the number of treatments and
      localization of stones in the ureter, as well as a statistically significant
      correlation between the size of the stone and the localization of calculus in the
      ureter.

PMID- 25568626
TI  - The pulmonary thromboembolism as a risk of surgical treatments and the role of
      anticoagulant prophylaxiss.
AB  - OBJECTIVE: Our objective is to show the number of patients with postoperative
      pulmonary thromboembolism (PPTE) treated in Intensive care unit of Clinic for
      pulmonary diseases an TB "Podhrastovi" in three-year period : from June 1, 2011 -
      June 1, 2014 and to indicate the importance of various surgical operations in the
      development of pulmonary thromboembolism (PTE). MATERIAL AND METHODS: This is the
      retrospective study which shows the number of patients with PPTE treated in
      Intensive care unit of Clinic for pulmonary diseases an TB "Podhrastovi" in three
      year period : from 01.06.2011.-01.06.2014. It represents the number of these
      patients, per cent of patients with PPTE of total patients with PTE, age and sex
      of patients, type of surgery, period expressed in days from surgery to diagnosis
      of PTE, presence of deep venous thrombosis (DVT) of lower extremities,
      massiveness of PPTE e.g. level of pulmonary artery with embolus. RESULTS: In
      three-year period 232 patients with PTE were treated in Intensive care unit of
      Clinic "Podhrastovi". 60 of them or 25.86% were patients with 24 males or 40%
      middle-aged 58.5 years, and 36 females or 60% middle-aged 56.3 years. PPTE
      developed in 15 patients with abdominal, 11 with urologic, 8 with gynecologic, 15
      with orthopedic, 4 with cardiologic, 2 with vascular, 3 with neurosurgical, 1
      with glandular and 1 with orl operations. The average period from operation to
      diagnosis of PPTE was 10.5 days for women, and 13.8 days for men. Only two
      patients had acute DVT after operation (one man and one woman), and five had
      amnesias of previous DVT or PTE. The level or the site of pulmonary embolus was
      different from segmental to main branches of pulmonary artery. CONCLUSION:
      Different surgical operations are the big risk factor for the development of PTE.
      There is great significance of anticoagulant prophylaxis before surgery even in
      patients with no anamnesis of previous DVT or PTE.

PMID- 25568627
TI  - Relationship of weight and body mass index with bone mineral density in adult men
      from kosovo.
AB  - BACKGROUND AND OBJECTIVE: Body weight and body mass index (BMI) are considered
      strong predictors of osteoporotic fractures, though optimal BMI levels remain
      unsettled. There are several studies conducted on women about the relationship
      between BMI and bone mineral density (BMD), and just a few so far on men.
      Therefore, the objective of current study was to analyze the relationship between
      weight and BMI and BMD measured in lumbar spine (L1-L4), femur neck and total hip
      in 64 men from Kosovo. METHODS: This cross-sectional study included a population
      of 64 men divided into three BMI groups. Dual-energy X-ray absorptiometry (DEXA)
      measurements were done in all the study participants. RESULTS: Pearson's
      correlation analysis showed a significant positive correlation between weight and
      BMI and BMD in femur neck and in total hip, and a significant negative
      correlation between age and femur neck BMD. Age-adjusted linear regression
      analysis showed that weight and BMI had a significant positive association with
      BMD levels. CONCLUSION: Although the results show significant relationship
      between BMI and BMD, the negative relationship between age and femur neck BMD may
      serve as guidance to initiate early assessment of the BMD in this region as well
      as preventive measures of osteoporosis and fractures among ageing men population.

PMID- 25568628
TI  - Assessments of the socioeconomic status and diet on the prevalence of dental
      caries at school children in central bosnian canton.
AB  - AIM: The main aim of this research was to determine the influence of
      socioeconomic status and residence/living conditions on the status of oral health
      (e.g. health of mouth and teeth) in primary school students residing in Canton
      Central Bosnia. METHODS: The study was designed as a cross-sectional study. Our
      research included two-phased stratified random sample of 804 participants. The
      quantitative research method and newly designed survey instrument were utilized
      in order to provide data on the oral health of the examined children. The
      alternate hypothesis foresaw that "there were significant statistical differences
      between the levels of incidence of dental caries in comparison to the incidence
      in children of different socioeconomic status. RESULTS: The Chi square () of
      22.814, degree of freedom (Df) = 8, coefficient of contingency of 0.163 and T
      test (Stat) of-0.18334 showed that there were no significant statistical
      differences at p < 0.05 level between the primary school children from urban and
      rural areas. The obtained results showed that the caries indexes in elementary
      schools in Central Bosnia Canton were fairly uniform. Research showed that there
      were a difference in the attitudes towards a regular dental visits, which
      correlated with social-educational structure of the children's' families.
      CONCLUSION: According to the results, we can see that the socioeconomic status of
      patients had an effect on the occurrence of dental caries and oral hygiene in
      patients in relation to the rural and urban areas, because we can see that by the
      number of respondents, the greater unemployment of parents in both, rural and
      urban areas, caused a host of other factors, which were, either, directly or
      indirectly connected with the development of caries.

PMID- 25568629
TI  - Investigation of the relationship between organizational learning and
      organizational citizen behavior among the staff of teaching hospital.
AB  - BACKGROUND: Today, the concept of organizational learning has attracted the
      attention of many managers and researchers in scientific and research circles as
      well as those in the organization-related studies. Taking the organizational
      learning into account might offer a means of organizational effectiveness that
      has gone unnoticed. Thus the present study aimed at investigating the
      relationship between the organizational learning in each of its four aspects as
      independent variables and organizational citizen behavior of the staff as
      constituting the dependent variable of the study. METHODS: This was a descriptive
      analytical study with a practical approach conducted in 2010. The sample included
      167 staff members working in educational health centers affiliated with Qazvin
      University of Medical Sciences. The data were collected via both the
      organizational learning questionnaire and organizational citizen behavior
      questionnaire and analyzed by using SPSS software and Spearman test. RESULTS: The
      results indicated that the mean of organizational learning indicator was 2.9+/
      0.648 and that of organizational citizen behavior 3.78+/-0.413. In addition, the
      spearman correlation coefficient ranging from 0.058 to 0.129 between the elements
      of the organizational learning and the organizational citizen behavior was not
      statistically significant (p>0.05). The findings also indicated that the
      correlation between them was average among the staff of Shahid Raja'ee
      Educational health center (0.319), thus the relationship between the two sets of
      variables proved significant (p=0.031). However, the same was not true in other
      centers. CONCLUSION: It was concluded that management commitment, open space,
      transfer of knowledge, and systemic vision could all enhance the level of
      organizational learning in hospitals which calls for focus on the elements of
      organizational citizen behavior.

PMID- 25568630
TI  - Effect of diet education on blood pressure changes and interdialytic weight in
      hemodialysis patients admitted in hajar hospital in shahrekord.
AB  - BACKGROUND AND AIM: Nutrition is a key factor in the treatment of patients with
      chronic kidney disease because kidney burden decrease causes uremic reduction and
      its side effects. The aim of this research is to examine the effect of diet
      education on blood pressure changes and interdialytic weight in Hemodialysis
      patients admitted to Hemodialysis ward of Hajar hospital in Shahrekord. METHODS:
      This quasi-experimental and interventional study of 100 dialysis patients
      referred to Hemodialysis ward of Hajar hospital was performed in a pre-test and
      post-test in 2011. Diet education, including face to face training with
      instruction booklets, were conducted in the two sessions. Having carried out the
      educational program, blood pressure and interdialytic weight gain were measured
      and recorded one month before and during three stages and after the educational
      program by researcher-designed checklists. The data were analyzed through Spss16
      software by Paired t-test and ANOVA. RESULTS: The results showed that mean of
      primary weight of the patients increase from 66.15+/-15.10 to 64.43+/-14.67. Mean
      of Systolic and diastolic blood pressure in patients in three stages were reduced
      to 6.65+/-1.51 mmg 2.24+/-1.82 mmg respectively. There was a significant
      difference between the creatinine amount in patients before and after of training
      (p<=0.01) but no meaningful difference was observed between the BUN amount before
      and after of training (p<=0.031). CONCLUSION: Training to patients underwent
      hemodialysis in order to observe diet and its effects on improvement in treatment
      are of significant importance.

PMID- 25568631
TI  - Effect of sperm count on success of intrauterine insemination in couples
      diagnosed with male factor infertility.
AB  - OBJECTIVE: To exam semen parameters in predicting intrauterine insemination (IUI)
      outcomes in couples with male factor. STUDY DESIGN: This retrospective study was
      performed at department of infertility and sexual medicine from September 2007 to
      February 2014. 307 couples with male factor infertility were included and 672 IUI
      cycles were analyzed. RESULTS: From 672 inseminations performed on 307 couples,
      there are 27.36% couples get pregnancy (84 out of 307) and the overall pregnancy
      rate was 12.95% (87 out of 672) of IUI. With the increase of post total
      progressive sperm count, the clinical pregnancy rate increased. When the initial
      progressive sperm count was lower than 5*10(6), there was no pregnant in the IUI
      cycle. At the end of the third cycle, 85 clinical pregnancies had been achieved
      (97.70%). CONCLUSIONS: The initial total progressive sperm count lower than
      5*10(6) means the poor outcome of IUI in the infertile couples with male factor.
      If the infertile couples with male factor don't get pregnancy after three IUI
      cycles, the couples should receive re-assessment or other artificial reproductive
      technology.

PMID- 25568632
TI  - Assessment of interpersonal communication skills among sari health centers'
      staff.
AB  - BACKGROUND AND AIM: Ability to communicate correctly has been one of the life's
      basic social skills and its significance in human life is to some extent that
      some of the experts attribute the human growth foundation owners of the leading
      personal injuries and progress to human relationship. Purpose of this study was
      to evaluate the interpersonal communication skills among the health care centers
      staff. METHODS: This study was a descriptive-cross sectional study was done among
      85 staff in 12 metropolitan and 9 urban health centers in 2013. According to
      Kerejsi and Morgan's table, 70 employees were determined as samples. Seventy
      questionnaires were distributed at the mentioned centers and 60 measurable health
      questionnaires were examined. Demographic data and measure of communication
      skills: is a 36-items consisting of seven domains: (general Communication,
      speaking, listening, interpretation and clarification, asking, feedback, and
      reward and punishment), obtained data were analyzed by inferential statistical
      tests (Mann-Whitney U, Kruskal-Wallis and correlation coefficient). RESULTS: Most
      respondents 38 (63.3%) were women, 57 (95%) married and 17 (28.1 %) age means of
      43-47 years. In the study status of the communication skills status of employees
      employed in health centres, Sari, "Punish and encourage skills" with mean and
      total standard deviation of 4.11+/-37.0 assigned the highest score and "feedback"
      skill with mean and total standard deviation of 3.68+/-045 assigned the less
      score. CONCLUSION: Findings showed that public relation skill, listening, reward
      and punishment in good scope and other skills were in the average scope. No need
      for training skills of empowerment of staff and their mental health. These
      results could be used for developing similar instruments in other health workers.

PMID- 25568633
TI  - Work stress and risk factors for health management trainees in canakkale, Turkey.
AB  - AIM: This study aims to investigate the general mental health situation, work
      related stress and risk factors of health management trainees. METHODS: This
      cross-sectional study was conducted on Health Management Musters students (N=96)
      in Canakkale Onsekiz Mart University Health Sciences Institute, May-June 2014. A
      total of 58 students who voluntarily participated in the study were reached
      (60.42%). Participants completed a 22-question sociodemographic survey form and a
      12-item General Health Questionnaire in a face-to-face interview. Data were
      analyzed using the SPSS software version 20.0. RESULTS: The average age of
      participants was 36.4+/-6.2 (Min:24-Max:62) years. Thirty five of the
      participants were female (60.3%), 23 were male (39.7%). The number of people
      using cigarettes and alcohol were 23 (39.7%) and 9 (15.8%) respectively. In our
      study group according to GHQ scale 32 people (55.2%) were in the group at risk of
      depression. Eighty-six percent of participants reported experiencing work stress.
      The most frequently reported sources of stress were superiors (56.8%), work
      itself (41.3%), and work colleagues (25.8%). There was no significant difference
      between those at risk of depression and those not at risk in terms of gender,
      marital status, educational level, age, work-related factors (daily work,
      computer use, duration of sitting at desk), sleep duration, presence of chronic
      disease, substance use (cigarettes, alcohol), regular exercise, regular meals,
      fast-food consumption, sufficient family time and vacations (p>0.05).
      CONCLUSIONS: Our study results indicated that majority of participants reported
      experiencing work stress with more than half at high risk of developing
      depression. The most reported risk factors were superiors, the work itself and
      colleagues in the present study. Psychosocial risk factors at work environment
      should be investigated in terms of psychological, sociological and ergonomics in
      more detail to reduce the risk of health management trainees experiencing work
      stress and mental health problems.

PMID- 25568634
TI  - Characteristics of rotavirus diarrhea in hospitalized children in kosovo.
AB  - BACKGROUND: Diarrhea is a leading cause of child mortality worldwide. Rotavirus
      is one of the most common causes of severe diarrhea and dehydration in children.
      Authors reviewed epidemiological and clinical data of the rotavirus diarrhea in
      Kosovo. METHODS: This is a prospective study carried between January 1st and
      December 31st 2011. All data, comprising demographics, nutrition, clinical
      presentation, laboratory findings, management and outcome of the rotavirus
      diarrhea are collected on the specially designed form. RESULTS: 116 children with
      rotavirus diarrhea are included in the study. The majority boys (74.4%) and
      children aged 0 - 12 months (82.75%). Mean age of children in the study was 16.38
      months. Almost every third child in the study was hypotrophic (29.2%). More than
      half of the infants (55.2%) were on mixed food, somewhat more than every third
      was breast feeding (36.45%), and every twelfth (8.33%) was on artificial milk
      (animal or formula). Apart from diarrhea, present in all patients, vomiting
      (97.41%) and fever (43.96%) were characteristics of the clinical presentation of
      the diarrhea. Two thirds of the children had mild grade dehydration (70.7%). All
      patients recovered with no sequels. CONCLUSION: Rotavirus continues to be
      responsible for a significant portion of acute diarrhea in Kosovo. Clinical
      features, epidemiological data and the agglutination test are safe enough to
      establish the diagnosis. Treated correctly rotavirus diarrhea has a favorable
      outcome.

PMID- 25568635
TI  - Cost of illness of tuberculosis in tehran in the year 2011.
AB  - AIM: Present study calculates and analyzes Cost of illness of tuberculosis in
      Tehran. PATIENTS AND METHODS: This study was a descriptive analytical study
      conducted among 121 patients in two stages in 2011. In the first stage,
      questionnaires were collected by reviewing patient records and phone interviews
      with patients. The second stage deals with the calculation of costs. For cost
      calculation, we used incidence based and bottom-up approach, and for calculating
      indirect costs, human capital approach was used. The vision used for this study
      was community-based in which all costs are included. RESULT: The average costs
      per patient were calculated to be as follows: 28,467,737 Rials(2588 dollars) for
      direct medical costs, 1,011,360 Rials (92 dollars) for indirect medical costs and
      5,533,020 (503 dollars) Rials for indirect costs. On the whole, average costs per
      patient was 35,056,170 Rials most of which were related to hospital costs
      (62/11%). Also, the average time away from work was 47 days. Cost calculated for
      all patients with tuberculosis in Tehran in 1390, including indirect costs caused
      by premature deaths of patients, was 101,900,501,328 Rials (9,263,681 U.S.$).
      CONCLUSION: To sum up, in Tehran in 2011 on average every day about 279,179,456
      Rials (25,380 dollars) was spent on TB patients. Moreover, heavy costs caused by
      TB, which are usually imposed to the households in two or three months, have
      significant effect of decreasing households' quality of life which calls health
      policy makers' attention.

PMID- 25568636
TI  - Communication patterns in preschool education institutions - practical examples.
AB  - INTRODUCTION: Proper communication in pre-school institutions for education is
      undeniable importance to the development of the child, as evidenced by numerous
      studies. After the child's birth follows the most complex phase in its early
      phases - preschool education. Only high-quality, synergistic relationship triad:
      parent-child-educator and the modern postulates of preschool child education,
      warrants successful preschool child education. METHODS AND MATERIALS:
      Description, with examples from daily practice in a large institution for
      preschool education, marked were the critical points on the complex way in child
      education, many pitfalls encountered by both parents and educators. Considered
      are the errors in communication with the proposed solution to avoid the same in
      practice. CONCLUSION: Proper, daily communication in the preschool institution
      for education, within a relationship between parent-child-educator, mutual
      consultation, respect, acceptance, facilitation, resulting in successful common
      goal - the proper education and socialization of children in institutions for
      preschool education.

PMID- 25568637
TI  - Tretatment approach of nontransplant patients with multiple myeloma.
AB  - Multiple myeloma is still an incurable disease with pattern of regression and
      remission followed by multiple relapses raising from the residual myeloma cells
      surviving even in the patients who achieve complete clinical response to
      treatment. In recent years there is a huge improvement in treatment of patients
      with multiple myeloma. The milestones of these improvement are: autologous
      transplantation and high-dose melphalan, imunomodulating drugs (thalidomide,
      lenalidomide), proteosom inhibitors (bortesomib, carfilzomib). The most
      significant improvement in overall survival has been achieved in the patients
      younger than 65 years. So, the major challenge for hematologist is to translate
      this improvement in the elderly patients with multiple myeloma. Today, physicians
      are able to offer wider variety of treatment options for elderly patients with
      multiple myeloma. Therapeutic options should be tailored and personalized
      according to patient's characteristics by balancing efficacy and toxicity of each
      drug which is especially important for elderly patients. In the mode of
      sequencing treatment for elderly patients with multiple myeloma, our goal is to
      achieve and maintain maximal response while limiting treatment -related
      toxicities as much as possible. Second-generation novel agent, such as
      carfilzomib, pomalidomide, elotuzumab, bendamustine are currently being evaluated
      as an option to improve treatment outcome in elderly patients. 

PMID- 25568639
TI  - A Case Study Exploring Research Communication and Engagement in a Rural Community
      Experiencing an Environmental Disaster.

PMID- 25568638
TI  - Maternal Attachment Style and Responses to Adolescents' Negative Emotions: The
      Mediating Role of Maternal Emotion Regulation.
AB  - OBJECTIVE: Previous research has examined the developmental consequences,
      particularly in early childhood, of parents' supportive and unsupportive
      responses to children's negative emotions. Much less is known about factors that
      explain why parents respond in ways that may support or undermine their
      children's emotions, and even less is known about how these parenting processes
      unfold with adolescents. We examined the associations between mothers' attachment
      styles and their distress, harsh, and supportive responses to their adolescents'
      negative emotions two years later and whether these links were mediated by
      maternal emotion regulation difficulties. DESIGN: Mothers in a longitudinal study
      (n = 230) reported on their attachment style, difficulties regulating their
      emotions, and their hypothetical responses to their adolescents' negative
      emotions, respectively, at consecutive laboratory visits one year apart. RESULTS:
      Mothers who reported greater attachment-related avoidance and anxiety reported
      having greater difficulties with emotion regulation one year later. Emotion
      dysregulation, in turn, predicted more distressed, harsher, and less supportive
      maternal responses to adolescents' negative emotions the following year. In
      addition, greater avoidance directly predicted harsher maternal responses two
      years later. CONCLUSIONS: These findings extend previous research by identifying
      maternal attachment style as a predictor of responses to adolescent distress and
      by documenting the underlying role of emotion dysregulation in the link between
      adult attachment style and parenting.

PMID- 25568640
TI  - Sexuality and Intimacy in Assisted Living: Residents' Perspectives and
      Experiences.
AB  - The assisted living industry provides residential, medical, nutritional,
      functional, and social services for approximately 1 million older adults in the
      United States. Despite their holistic approach to person-centered care and their
      emphasis on a consumer-empowered, social environment, assisted living providers
      pay scant attention to clients' sexual needs. In this article, the authors
      discuss the realities of sex and intimacy in assisted living from the
      perspectives of residents, families, managers, and staff, exploring the discourse
      of sexuality, the impact of institutional structure and the role of oversight on
      sexual attitudes and behaviors, and the relationship of assisted living industry
      values to residents' sexual expression. Also presented are practical
      recommendations and policy implications for addressing the sexual and intimacy
      needs of current and future cohorts of assisted living residents. Data for this
      article were drawn from 3 National Institute on Aging-funded ethnographic studies
      conducted in 13 assisted living settings over 9 years.

PMID- 25568641
TI  - A Preliminary Assessment of the Structure-Activity Relationship of Benzimidazole
      Based Anti-Proliferative Agents.
AB  - PDK1 is pivotal in the development and progression of several cancers. A 3D
      pharmacophore was developed for pyrazole derivatives displaying anti
      proliferative activity and PDK1 inhibition. The pharmacophore was utilized in the
      design of benzimidazole analogs. Our preliminary results indicate the
      pharmacophore should be useful in designing PDK1 inhibitors and anti
      proliferative agents.

PMID- 25568642
TI  - Reinforcement of Shear Thinning Protein Hydrogels by Responsive Block Copolymer
      Self-Assembly.
AB  - Shear thinning hydrogels are promising materials that exhibit rapid self-healing
      following the cessation of shear, making them attractive for a variety of
      applications including injectable biomaterials. In this work, self-assembly is
      demonstrated as a strategy to introduce a reinforcing network within shear
      thinning artificially engineered protein gels, enabling a responsive transition
      from an injectable state at low temperatures with a low yield stress to a
      stiffened state at physiological temperatures with resistance to shear thinning,
      higher toughness, and reduced erosion rates and creep compliance. Protein-polymer
      triblock copolymers capable of the responsive self-assembly of two orthogonal
      networks have been synthesized by conjugating poly(N-isopropylacrylamide) to the
      N- and C- termini of a protein midblock decorated with coiled-coil self
      associating domains. Midblock association forms a shear-thinning network, while
      endblock aggregation at elevated temperatures introduces a second, independent
      physical network into the protein hydrogel. These new, reversible crosslinks
      introduce extremely long relaxation times and lead to a five-fold increase in the
      elastic modulus, significantly larger than is expected from transient network
      theory. Thermoresponsive reinforcement reduces the high temperature creep
      compliance by over four orders of magnitude, decreases the erosion rate by at
      least a factor of five, and increases the yield stress by up to a factor of
      seven. The reinforced hydrogels also exhibit enhanced resistance to plastic
      deformation and failure in uniaxial compression. Combined with the demonstrated
      potential of shear thinning artificial protein hydrogels for various uses,
      including the minimally-invasive implantation of bioactive scaffolds, this
      reinforcement mechanism broadens the range of applications that can be addressed
      with shear-thinning physical gels.

PMID- 25568645
TI  - From the Editor-in-Chief.

PMID- 25568644
TI  - Regulation and function of stimulus-induced phosphorylation of MeCP2.
AB  - DNA methylation-dependent epigenetic regulation plays important roles in the
      development and function of the mammalian nervous system. MeCP2 is a key player
      in recognizing methylated DNA and interpreting the epigenetic information encoded
      in different DNA methylation patterns. Mutations in the MECP2 gene cause Rett
      syndrome, a devastating neurological disease that shares many features with
      autism. One interesting aspect of MeCP2 function is that it can be phosphorylated
      in response to diverse stimuli. Insights into the regulation and function of
      MeCP2 phosphorylation will help improve our understanding of how MeCP2 integrates
      environmental stimuli in neuronal nuclei to generate adaptive responses and may
      eventually lead to treatments for patients.

PMID- 25568643
TI  - Genome-wide antagonism between 5-hydroxymethylcytosine and DNA methylation in the
      adult mouse brain.
AB  - Mounting evidence points to critical roles for DNA modifications, including 5
      methylcytosine (5mC) and its oxidized forms, in the development, plasticity and
      disorders of the mammalian nervous system. The novel DNA base 5
      hydroxymethylcytosine (5hmC) is known to be capable of initiating passive or
      active DNA demethylation, but whether and how extensively 5hmC functions in
      shaping the post-mitotic neuronal DNA methylome is unclear. Here we report the
      genome-wide distribution of 5hmC in dentate granule neurons from adult mouse
      hippocampus in vivo. 5hmC in the neuronal genome is highly enriched in gene
      bodies, especially in exons, and correlates with gene expression. Direct genome
      wide comparison of 5hmC distribution between embryonic stem cells and neurons
      reveals extensive differences, reflecting the functional disparity between these
      two cell types. Importantly, integrative analysis of 5hmC, overall DNA
      methylation and gene expression profiles of dentate granule neurons in vivo
      reveals the genome-wide antagonism between these two states of cytosine
      modifications, supporting a role for 5hmC in shaping the neuronal DNA methylome
      by promoting active DNA demethylation.

PMID- 25568646
TI  - Pain pharmacology: focus on opioids.
AB  - The incidence of chronic pain is estimated to be 20-25% worldwide. Although major
      improvements in pain control have been obtained, more than 50% of the patients
      reports inadequate relief. It is accepted that chronic pain, if not adequately
      and rapidly treated, can become a disease in itself, often intractable and maybe
      irreversible. This is mainly due to neuroplasticity of pain pathways. In the
      present review I will discuss about pain depicting the rational for the principal
      pharmacological interventions and finally focusing on opioids, that represent a
      primary class of drug to treat pain. 

PMID- 25568647
TI  - Pathogenesis and clinical aspects of pain in patients with osteoporosis.
AB  - Bone pain is one of the most frequent kinds of chronic pain, mainly in elderly
      patients. It causes a significant worsening of functional capacity and
      deterioration in the quality of life in people affected. Mechanisms of pain in
      osteoporosis are poorly known and often extrapolated by other pathologies or
      other experimental model. One of principal causes would be a "hyper-remodeling"
      of bone, that involves osteoclasts activity and pathological modifications of
      bone innervation. Several studies show that osteoclasts play a significant role
      in bone pain etiology. Pain in osteoporosis is mainly nociceptive, if it become
      persistent a sensitization of peripheral and central nervous system can occur, so
      underlining the transition to a chronic pain syndrome. Central sensitization
      mechanisms are complex and involve several neuromediators and receptors
      (Substance P, NMDA, etc.). Most common manifestations of osteoporosis are
      vertebral compression fractures that cause persistent pain, though to
      differentiate from pain originating in structures as joint or muscle. First
      manifestation can be an acute pain due to pathological fracture, those of hip
      often causes disability. Pain in osteoporosis is an important clinical challenge.
      Often its complications and consequences on patient quality of life are
      underestimated with not negligible social implications. A balanced and early
      multimodal pain therapy including opioids as necessary, even in cases of acute
      pain, improve the functional capacity of patients and helps to prevent
      neurological alterations that seems to contribute in significant way in causing
      irreversible pain chronic syndromes. 

PMID- 25568648
TI  - Use of opioids for treatment of osteoporotic pain.
AB  - The prevalence of osteoporosis increases markedly with age: currently it is
      estimated that over 200 million people suffer from osteoporosis worldwide. One of
      the most feared and more frequent complications of osteoporosis is pain, which
      affects 85% of patients. Commonly in the treatment of chronic pain the
      therapeutic strategy is based on a three-ladder approach, involving opioids for
      moderate and severe pain. As proposed by the World Health Organization (WHO),
      according to the intensity of chronic pain, analgesic treatment can be
      established. Despite the debate and updates to the analgesic ladder for pain
      published in 1986 by the WHO, the benefits resulting from its worldwide use are
      uncontested. In case the pain was not responsive to drugs of pain ladder, is
      necessary to resort to specialized practices (e.g. subarachnoid infusion of
      drugs). The oral route for administering analgesics should be preferred, provided
      that the patients are able to use it. About 50% of all opioid users experience at
      least one side effect, and more than 20% discontinued treatment due to a serious
      adverse event. Despite published guidelines and WHO's pain ladder for the
      management of chronic pain, the treatment of this condition remains suboptimal.
      Given the physiopsychopathology and complexity of the problems of chronic
      osteoporotic pain, a multimodal and multidisciplinary approach is still
      considered the best way to diagnose and treat this disease. 

PMID- 25568649
TI  - Clinical definition of sarcopenia.
AB  - Sarcopenia is a condition characterized by loss of skeletal muscle mass and
      function. Although it is primarily a disease of the elderly, its development may
      be associated with conditions that are not exclusively seen in older persons.
      Sarcopenia is a syndrome characterized by progressive and generalized loss of
      skeletal muscle mass and strength and it is strictly correlated with physical
      disability, poor quality of life and death. Risk factors for sarcopenia include
      age, gender and level of physical activity. In conditions such as malignancy,
      rheumatoid arthritis and aging, lean body mass is lost while fat mass may be
      preserved or even increased. The loss in muscle mass may be associated with
      increased body fat so that despite normal weight there is marked weakness, this
      is a condition called sarcopenic obesity. There is an important correlation
      between inactivity and losses of muscle mass and strength, this suggests that
      physical activity should be a protective factor for the prevention but also the
      management of sarcopenia. Furthermore one of the first step to be taken for a
      person with sarcopenia or clinical frailty is to ensure that the sarcopenic
      patient is receiving correct and sufficient nutrition. Sarcopenia has a greater
      effect on survival. It should be important to prevent or postpone as much as
      possible the onset of this condition, to enhance survival and to reduce the
      demand for long-term care. Interventions for sarcopenia need to be developed with
      most attention on exercise and nutritional interventions. 

PMID- 25568650
TI  - Techniques for the diagnosis of sarcopenia.
AB  - Sarcopenia is an age-related process of skeletal muscle loss associated with
      declining physical performance, highly prevalent among older subjects, with a
      negative prognostic effect on falls, disability and mortality risk. Modern
      approaches to sarcopenia case finding and diagnosis are based on physical
      performance measures, while assessment of muscle mass represents the second
      diagnostic step. Muscle mass can be quantified at different levels of body
      composition, with a complexity increasing from atomic detection to anatomic
      measure. In the choice of measuring method, different factors have to be taken
      into account, including validity, simplicity, cost and specific purpose (clinical
      versus research). Some methods, such as MRI and CT, have high validity but are
      complex and costly. Bioelectrical impedance analysis is inexpensive and easy to
      perform in most settings, being the preferred method for clinical practice. Dual
      energy X-ray absorptiometry has intermediate cost and complexity with good
      reproducibility, and is more reliable for research setting. Other methods, such
      as administration of tritium (D3)-marked creatine and measurement of urinary D3
      creatinine, are still in a preclinical phase of development. For all methods the
      issue of normative data does exist and needs to be solved, in order to reliably
      identify homogeneous populations with sarcopenia, to be targeted in clinical
      practice and intervention studies. 

PMID- 25568652
TI  - Pharmacological prevention of venous thromboembolism in orthopaedic surgery.
AB  - The prophylaxis of venous thromboembolism (VTE) with anticoagulant drugs is a
      long-established practice in hip and knee replacement surgery, as well as in the
      treatment of femoral neck fractures, while there are few data regarding the
      prevention of VTE in other fields of orthopaedic surgery and traumatology. In
      order to provide practical recommendations for daily management of VTE
      prophylaxis in orthopaedic patients, recently the Italian Societies of Thrombosis
      and Haemostasis, Orthopaedics and Traumatology and Anaesthesia have drawn up a
      first Intersociety Consensus on antithrombotic prophylaxis in total hip and knee
      replacement surgery, and in the treatment of femoral neck fracture, then updated
      in 2013, and a subsequent Intersocietary Consensus, in cooperation also with the
      Society of general practitioners, concerning antithrombotic prophylaxis in other
      types of orthopaedic surgery and traumatology. Before starting any prophylactic
      treatment it is of crucial importance the assessment of both thrombotic and
      bleeding risk of patients undergoing surgery. Thromboembolic prophylaxis is
      recommended with low molecular weight heparins (LMWH), fondaparinux (FON) or with
      the new oral anticoagulants (NOA) in patients undergoing hip and knee replacement
      surgery while patients undergoing treatment of femoral neck fracture should be
      treated with LMWH or FON. Regarding the non-prosthetic orthopaedic surgery and
      traumatology, it is recommended prophylaxis with LMWH or FON in situations of
      high thromboembolic risk or in the case of interventions or trauma involving
      pelvis, acetabulum or knee. 

PMID- 25568653
TI  - The hip prosthesis in lateral femur fracture: current concepts and surgical
      technique.
AB  - The third proximal femur fractures are divided into medial and lateral ones. For
      medial fractures already exists unanimity of thought for the choice of treatment
      that involves the prosthetic replacement of the hip joint in patients over 60
      without indications to the synthesis. Regarding the lateral femur fractures this
      unanimity does not exist yet even if the majority of surgeons practice treatment
      with osteosynthesis. We want to highlight if there are any types of lateral
      fractures associated with patient's clinical condition in which it might be more
      useful to a prosthetic replacement with the aim of being able to allow a total
      load and earlier deambulation, reducing complications related to a possible
      patient immobilization. 

PMID- 25568651
TI  - Hepatic osteodystrophy.
AB  - Metabolic disturbances of bone are frequent in patients with chronic liver
      disease. The prevalence of osteoporosis among patients with advanced chronic
      liver disease is reported between 12% and 55%; it is higher in primary biliary
      cirrhosis. All patients with advanced liver disease should be screened for
      osteoporosis with a densitometry, especially if the etiology is cholestatic and
      in the presence of other risk factors. Clinical relevance of hepatic
      osteodystrophy increases after liver transplantation. After liver transplant, a
      rapid loss of bone mineral density can be detected in the first 6 months,
      followed by stabilization and slight improvement of the values. At the time of
      transplantation, bone density values are very important prognostic factors.
      Therapy of hepatic osteodystrophy is based primarily on the control of risk
      factors: cessation of tobacco and alcohol assumption, reduction of caffeine
      ingestion, exercise, supplementation of calcium and vitamin D, limitation of
      drugs such as loop diuretics, corticosteroids, cholestyramine. Bisphosphonates
      have been proposed for the therapy of osteoporosis in patients with liver
      disease, particularly after liver transplantation. The possible side effects of
      oral administration of bisphosphonates, such as the occurrence of esophageal
      ulcerations, are of particular concern in patients with liver cirrhosis and
      portal hypertension, due to the risk of gastrointestinal hemorrhage from ruptured
      esophageal varices, although this risk is probably overestimated. 

PMID- 25568655
TI  - Updates on mechanism of action and clinical efficacy of risedronate in
      osteoporosis.
AB  - Risedronate is a heterocyclic orally active aminobisphosphonate and it belongs to
      the bisphosphonate category: these drugs are powerful bone resorption inhibitors,
      thanks to their affinity for hydroxyapatite crystals at bone mineral matrix level
      and to their inhibiting effects on osteoclast activity, using the ability of
      inhibiting enzyme FPPS. Recent observations have reported that risedronate can
      decrease resorption entity, not only of the trabecular bone, but also of the
      cortical bone, modifying therefore the (bone compact) thickness and the cortical
      porosity entity, which is largely responsible of femoral fracture especially
      among elderly patients. Various controlled studies have proved the efficacy of
      risedronate in reducing fragility fracture risk significantly. In particular, it
      is able to lower in a very significant way the incidence of vertebral, non
      vertebral and femoral fractures, with precocity of effects after only six months
      of therapy. The extension of protocols, moreover, has marked its efficacy even
      after seven years of treatment. Under the metabolic profile, these studies have
      also shown that risedronate activity can reduce bone resorption markers and
      increase bone density values at lumbar and femoral level. Results emerged from a
      group of women aged over 80 are relevant: risedronate has proved capable of
      decreasing femoral fracture risk. Also in male and steroidal osteoporosis,
      clinical controlled studies have shown that risedronate is effective in
      decreasing vertebral fracture incidence. Lastly, tolerability: the main side
      effects concern the gastrointestinal tract and they are usually rare, of minor
      entity and can be solved by sospending the treatment. Acute phase reaction is
      rare, due to risedronate oral administration; it is also valid for osteonecrosis
      of the jaw and atypical fractures. 

PMID- 25568654
TI  - Screening, diagnosis and treatment of osteoporosis: a brief review.
AB  - Osteoporosis is a highly prevalent condition characterized by decreases in bone
      mass and microarchitectural alterations. Bone fractures, especially of the hip
      and vertebrae, are the most burdensome complications of osteoporosis, being
      associated with high risk of disability, institutionalization and mortality. The
      detection of osteoporosis relies on the quantification of bone mineral density
      via imaging techniques such as dual-energy X-ray absorptiometry. However,
      therapeutic decision-making should be based on a comprehensive fracture risk
      assessment, which may be obtained through validated algorithms. Once the decision
      of treating has been taken, non-pharmacological strategies should be implemented
      together with the prescription of anti-osteoporotic agents. Numerous drugs are
      currently available to treat osteoporosis and the choice of a specific compound
      should be guided by efficacy and safety considerations. The present review
      provides a concise synopsis of the current evidence in the management of
      osteoporosis, from screening to drug prescription. Novel anti-osteoporotic agents
      are also briefly presented. 

PMID- 25568657
TI  - Pathogenesis and treatment of falls in elderly.
AB  - Falls in the elderly are a public health problem. Consequences of falls are
      increased risk of hospitalization, which results in an increase in health care
      costs. It is estimated that 33% of individuals older than 65 years undergoes
      falls. Causes of falls can be distinguished in intrinsic and extrinsic
      predisposing conditions. The intrinsic causes can be divided into age-related
      physiological changes and pathological predisposing conditions. The age-related
      physiological changes are sight disorders, hearing disorders, alterations in the
      Central Nervous System, balance deficits, musculoskeletal alterations. The
      pathological conditions can be Neurological, Cardiovascular, Endocrine,
      Psychiatric, Iatrogenic. Extrinsic causes of falling are environmental factors
      such as obstacles, inadequate footwear. The treatment of falls must be
      multidimensional and multidisciplinary. The best instrument in evaluating elderly
      at risk is Comprehensive Geriatric Assessment (CGA). CGA allows better management
      resulting in reduced costs. The treatment should be primarily preventive acting
      on extrinsic causes; then treatment of chronic and acute diseases. Rehabilitation
      is fundamental, in order to improve residual capacity, motor skills, postural
      control, recovery of strength. There are two main types of exercises: aerobic and
      muscular strength training. Education of patient is a key-point, in particular
      through the Back School. In conclusion falls in the elderly are presented as a
      "geriatric syndrome"; through a multidimensional assessment, an integrated
      treatment and a rehabilitation program is possible to improve quality of life in
      elderly. 

PMID- 25568656
TI  - Physical exercise and sarcopenia in older people: position paper of the Italian
      Society of Orthopaedics and Medicine (OrtoMed).
AB  - Sarcopenia is the age-associated loss of skeletal muscle mass and function. It is
      a major clinical problem for older people and research in understanding of
      pathogenesis, clinical consequences, management, and socioeconomic burden of this
      condition is growing exponentially. The causes of sarcopenia are multifactorial,
      including inflammation, insulin resistance, changing endocrine function, chronic
      diseases, nutritional deficiencies and low levels of physical activity.
      Operational definition of sarcopenia combines assessment of muscle mass, muscle
      strength and physical performance. The diagnosis of sarcopenia should be based on
      having a low appendicular fat free mass in combination with low handgrip strength
      or poor physical functioning. Imaging techniques used for estimating lean body
      mass are computed tomography, magnetic resonance imaging, bioelectrical impedance
      analysis and dual energy X-ray absorptiometry, the latter considered as the
      preferred method in research and clinical use. Pharmacological interventions have
      shown limited efficacy in counteracting the age-related skeletal muscle wasting.
      Recent evidence suggests physical activity and exercise, in particular resistance
      training, as effective intervention strategies to slow down sarcopenia. The
      Italian Society of Orthopaedics and Medicine (Or-toMed) provides this position
      paper to present the update on the role of exercise on sarcopenia in the elderly.

PMID- 25568658
TI  - Densitometric evaluation of periprosthetic bone remodeling.
AB  - The application of Dual-energy X-ray absorptiometry (DEXA) in orthopaedic surgery
      gradually has been extended from the study of osteoporosis to different areas of
      interest like the study of the relation between bone and prosthetic implants. Aim
      of this review is to analyze changes that occur in periprosthetic bone after the
      implantation of a total hip arthroplasty (THA) or a total knee arthroplasty
      (TKA). In THA the pattern of adaptive bone remodeling with different cementless
      femoral stems varies and it appears to be strictly related to the design and more
      specifically to where the femoral stem is fixed on bone. Short stems with
      metaphyseal fixation allow the maintenance of a more physiologic load transfer to
      the proximal femur decreasing the entity of bone loss. Femoral bone loss after
      TKA seems to be related to the stress shielding induced by the implants while
      tibial bone remodeling seems to be related to postoperative changes in knee
      alignment (varus/valgus) and consequently in tibial load transfer. After both THA
      and TKA stress shielding seems to be an inevitable phenomenon that occurs mainly
      in the first year after surgery. 

PMID- 25568659
TI  - Rapid bone destruction in a patient with knee osteoarthritis. A case report and
      review of the literature.
AB  - We report the clinical outcome of an elderly man with knee osteoarthritis (OA)
      accompanied with recurring severe joint pain. He had no history of trauma to the
      affected knee. Plain radiographs and magnetic resonance imaging uncovered rapid
      and severe bone deformity, which likely led to the patient's progressed
      radiographic OA. These findings indicate that a pathophysiology of OA may be bone
      alterations. 

PMID- 25568660
TI  - Jacopo Ligozzi painter of fine naturalia and macabre skulls.

PMID- 25568661
TI  - Transcriptional profiling of reproductive development, lipid storage and molting
      throughout the last juvenile stage of the marine copepod Calanus finmarchicus.
AB  - INTRODUCTION: Calanus finmarchicus, a highly abundant copepod that is an
      important primary consumer in North Atlantic ecosystems, has a flexible life
      history in which copepods in the last juvenile developmental stage (fifth
      copepodid, C5) may either delay maturation and enter diapause or molt directly
      into adults. The factors that regulate this developmental plasticity are poorly
      understood, and few tools have been developed to assess the physiological
      condition of individual copepods. RESULTS: We sampled a cultured population of C.
      finmarchicus copepods daily throughout the C5 stage and assessed molt stage
      progression, gonad development and lipid storage. We used high-throughput
      sequencing to identify genes that were differentially expressed during
      progression through the molt stage and then used qPCR to profile daily expression
      of individual genes. Based on expression profiles of twelve genes, samples were
      statistically clustered into three groups: (1) an early period occurring prior to
      separation of the cuticle from the epidermis (apolysis) when expression of genes
      associated with lipid synthesis and transport (FABP and ELOV) and two nuclear
      receptors (ERR and HR78) was highest, (2) a middle period of rapid change in both
      gene expression and physiological condition, including local minima and maxima in
      several nuclear receptors (FTZ-F1, HR38b, and EcR), and (3) a late period when
      gonads were differentiated and expression of genes associated with molting (Torso
      like, HR38a) peaked. The ratio of Torso-like to HR38b strongly differentiated the
      early and late groups. CONCLUSIONS: This study provides the first dynamic
      profiles of gene expression anchored with morphological markers of lipid
      accumulation, development and gonad maturation throughout a copepod molt cycle.
      Transcriptomic profiling revealed significant changes over the molt cycle in
      genes with presumed roles in lipid synthesis, molt regulation and gonad
      development, suggestive of a coupling of these processes in Calanus finmarchicus.
      Finally, we identified gene expression profiles that strongly differentiate
      between early and late development within the C5 copepodid stage. We anticipate
      that these findings and continued development of robust gene expression
      biomarkers that distinguish between diapause preparation and continuous
      development will ultimately enable novel studies of the intrinsic and extrinsic
      factors that govern diapause initiation in Calanus finmarchicus.

PMID- 25568663
TI  - A Measure of Perceived Argument Strength: Reliability and Validity.
AB  - Studies of the content of persuasive messages in which the central arguments of
      the message are scrutinized have traditionally relied on the technique of thought
      listing to assess argument strength. Although the validity of the thought-listing
      procedure is well documented, its utility can be limited in situations involving
      non-adult populations and sensitive topics. In this paper we present a self
      reported scale that can be used to assess perceived argument strength in contexts
      where thought-listing may be less appropriate. This scale taps into perceived
      argument strength from multiple points of view, including but also extending
      beyond the potential of the argument to elicit positive and negative thoughts.
      Reliability and validity of this scale were assessed in health communication
      contexts involving anti-drug PSAs directed at adolescents and anti-smoking PSAs
      targeting adults. Evidence of convergence between this scale and the thought
      listing technique was also obtained using the classical comprehensive exam
      arguments.

PMID- 25568664
TI  - STAT activation status differentiates leukemogenic from non-leukemogenic stem
      cells in AML and is suppressed by arsenic in t(6;9)-positive AML.
AB  - Acute myeloid leukemia (AML) is characterized by an aberrant self-renewal of
      hematopoietic stem cells (HSC) and a block in differentiation. The major
      therapeutic challenge is the characterization of the leukemic stem cell as a
      target for the eradication of the disease. Until now the biology of AML
      associated fusion proteins (AAFPs), such as the t(15;17)-PML/RARalpha, t(8;21)
      RUNX1/RUNX1T1 and t(6;9)-DEK/NUP214, all able to induce AML in mice, was
      investigated in different models and genetic backgrounds, not directly comparable
      to each other. To avoid the bias of different techniques and models we expressed
      these three AML-inducing oncogenes in an identical genetic background and
      compared their influence on the HSC compartment in vitro and in vivo. These AAFPs
      exerted differential effects on HSCs and PML/RARalpha, similar to DEK/NUP214,
      induced a leukemic phenotype from a small subpopulation of HSCs with a surface
      marker pattern of long-term HSC and characterized by activated STAT3 and 5. In
      contrast the established AML occurred from mature populations in the bone marrow.
      The activation of STAT5 by PML/RARalpha and DEK/NUP214 was confirmed in
      t(15;17)(PML/RARalpha) and t(6;9)(DEK/NUP214)-positive patients as compared to
      normal CD34+ cells. The activation of STAT5 was reduced upon the exposure to
      Arsenic which was accompanied by apoptosis in both PML/RARalpha- and DEK/NUP214
      positive leukemic cells. These findings indicate that in AML the activation of
      STATs plays a decisive role in the biology of the leukemic stem cell. Furthermore
      we establish exposure to arsenic as a novel concept for the treatment of this
      high risk t(6;9)-positive AML. 

PMID- 25568665
TI  - mTORC2 modulates feedback regulation of p38 MAPK activity via DUSP10/MKP5 to
      confer differential responses to PP242 in glioblastoma.
AB  - Dual-specificity phosphatases (DUSPs) dephosphorylate MAP kinases (MAPKs)
      resulting in their inactivation. Activation of MAPK signaling leads to enhanced
      DUSP expression, thus establishing feedback regulation of the MAPK pathway. The
      DUSPs are subject to regulation at the post-translational level via
      phosphorylation resulting in alterations of protein stability. Here we report
      that mTORC2 function leads to stabilization of the p38 MAPK phosphatase, DUSP10,
      thereby inhibiting p38 activity. We demonstrate that mTORC2 binds DUSP10 and
      phosphorylates DUSP10 on serine residues 224 and 230. These phosphorylation
      events block DUSP10 turnover resulting in inactivation of p38 signaling. We
      further show that insulin-stimulated PI3K/mTORC2 signaling regulates DUSP10
      stability and p38 activity. Importantly, knockdown of DUSP10 or ectopic
      overexpression of nonphosphorylatable or phosphomimetic DUSP10 mutants was
      sufficient to confer differential mTOR kinase inhibitor responses to GBM cells in
      vitro and in murine xenografts. Finally, DUSP10 was shown to be overexpressed in
      a significant number of GBM patients. These data demonstrate the ability of the
      mTORC2 pathway to exert regulatory effects on the DUSP10/p38 feedback loop to
      control the cellular effects of mTOR kinase inhibitors in GBM and support the use
      of DUSP10 expression as a surrogate biomarker to predict responsiveness. 

PMID- 25568662
TI  - Nanomaterial interactions with and trafficking across the lung alveolar
      epithelial barrier: implications for health effects of air-pollution particles.
AB  - Studies on the health effects of air-pollution particles suggest that injury may
      result from inhalation of airborne ultrafine particles (<100 nm in diameter).
      Engineered nanomaterials (<100 nm in at least one dimension) may also be harmful
      if inhaled. Nanomaterials deposited on the respiratory epithelial tract are
      thought to cross the air-blood barrier, especially via the expansive alveolar
      region, into the systemic circulation to reach end organs (e.g., myocardium,
      liver, pancreas, kidney, and spleen). Since ambient ultrafine particles are
      difficult to track, studies of defined engineered nanomaterials have been used to
      obtain valuable information on how nanomaterials interact with and traffic across
      the air-blood barrier of mammalian lungs. Since specific mechanistic information
      on how nanomaterials interact with the lung is difficult to obtain using in vivo
      or ex vivo lungs due to their complex anatomy, in vitro alveolar epithelial
      models have been of considerable value in determining nanomaterial-lung
      interactions. In this review, we provide information on mechanisms underlying
      lung alveolar epithelial injury caused by various nanomaterials and on
      nanomaterial trafficking across alveolar epithelium that may lead to end-organ
      injury.

PMID- 25568666
TI  - DEPTOR is linked to a TORC1-p21 survival proliferation pathway in multiple
      myeloma cells.
AB  - We investigated the mechanism by which gene silencing of the mTOR inhibitor,
      DEPTOR, induces cytoreductive effects on multiple myeloma (MM) cells. DEPTOR
      knockdown resulted in anti-MM effects in several MM cell lines. Using an
      inducible shRNA to silence DEPTOR, 8226 MM cells underwent TORC1 activation,
      downregulation of AKT/SGK activity, apoptosis, cell cycle arrest and senescence.
      These latter cytotoxic effects were prevented by TORC1 paralysis (Raptor
      knockdown) but not by over-expression of AKT activity. In addition, DEPTOR
      knockdown-induced MM death was not associated with activation of the unfolded
      protein response, suggesting that enhanced ER stress did not play a role. In
      contrast, DEPTOR knockdown in 8226 cells induced p21 expression, independent of
      p53, and p21 knockdown prevented all of the cytotoxic effects following DEPTOR
      silencing. DEPTOR silencing resulted in p21 upregulation in additional MM cell
      lines. Furthermore, DEPTOR silencing in a murine xenograft model resulted in anti
      MM effects associated with p21 upregulation. DEPTOR knockdown also resulted in a
      decreased expression of p21-targeting miRNAs and transfection of miRNA mimics
      prevented p21 upregulation and apoptosis following DEPTOR silencing. Use of a
      shRNA-resistant DEPTOR construct ruled out off-target effects of the shRNA. These
      results indicate that DEPTOR regulates growth and survival of MM cells via a
      TORC1/p21 pathway and suggest an involvement of p21-targeted miRNAs. 

PMID- 25568667
TI  - RGS16, a novel p53 and pRb cross-talk candidate inhibits migration and invasion
      of pancreatic cancer cells.
AB  - Data collected since the discovery of p53 and pRb/RB1 suggests these tumor
      suppressors cooperate to inhibit tumor progression. Patients who have mutations
      in both p53 and RB1 genes have increased tumor reoccurrence and decreased
      survival compared to patients with only one tumor suppressor gene inactivated. It
      remains unclear how p53 and pRb cooperate toward inhibiting tumorigenesis. Using
      RNA expression profiling we identified 179 p53 and pRb cross-talk candidates in
      normal lung fibroblasts (WI38) cells exogenously coexpressing p53 and pRb.
      Regulator of G protein signaling 16 (RGS16) was among the p53 and pRb cross-talk
      candidates and has been implicated in inhibiting activation of several oncogenic
      pathways associated with proliferation, migration, and invasion of cancer cells.
      RGS16 has been found to be downregulated in pancreatic cancer patients with
      metastases compared to patients without metastasis. Expression of RGS16 mRNA was
      decreased in the pancreatic cancer cell lines tested compared to control.
      Expression of RGS16 inhibited migration of the BxPC-3 and AsPC-1 but not PANC-1
      cells and inhibited invasion of BxPC-3 and AsPC-1 cells with no impact on cell
      viability. We have identified for the first time p53 and pRb cross-talk
      candidates and a role for RGS16 to inhibit pancreatic cancer migration and
      invasion. 

PMID- 25568668
TI  - Tumor suppression by miR-31 in esophageal carcinoma is p21-dependent.
AB  - microRNA regulation network is important for the cancer genetic heterogeneity.
      Relative to the increasing numbers of microRNA's targets identified, upstream
      regulatory mechanisms that control functional microRNAs are less well-documented.
      Here, we investigated the function of miR-31, a pleiotropically-acting microRNA,
      in esophageal squamous cell cancer (ESCC). We demonstrated that miR-31 only
      exerted tumor-suppressive effects in TE-7 ESCC cells, but not in TE-1 ESCC cells,
      although both of these cell lines harbor inactive p53. Interestingly, TE-1 cells
      highly expressed p21, while p21 levels were virtually undetectable in TE-7 cells,
      suggesting a p21-dependent mechanism of miR-31-mediated tumor suppression.
      Accordingly, knockdown of p21 in TE-1 cells reversed the tumor suppressive
      actions of miR-31. In patient ESCC specimens, real-time RT-PCR analysis revealed
      that expression of E2F2 and STK40, two known miR-31 target oncogenes, was
      negatively correlated with the expression of miR-31 in a p21-dependent manner,
      supporting the conclusion that miR-31 only downregulates its target oncogenes
      when p21 levels are low. Collectively, these data suggest a novel mechanism
      through which the tumor-suppressive effect of miR-31 is p21-dependent. In
      addition, we speculate that delivery of miR-31 could provide therapeutic benefit
      in the personalized management of a subgroup of ESCC patients with p21-deficient
      tumors. 

PMID- 25568669
TI  - The Bcl-2 inhibitor Obatoclax overcomes resistance to histone deacetylase
      inhibitors SAHA and LBH589 as radiosensitizers in patient-derived glioblastoma
      stem-like cells.
AB  - Glioblastoma has shown resistance to histone deacetylase inhibitors (HDACi) as
      radiosensitizers in cultures with Bcl-XL over-expression. We study the efficacy
      of SAHA/RTx and LBH589/RTx when manipulating Bcl-2 family proteins using the Bcl
      2 inhibitor Obatoclax in patient-derived glioblastoma stem-like cell (GSC)
      cultures. GSC cultures in general have a deletion in phosphatase and tensin
      homolog (PTEN). Synergy was determined by the Chou Talalay method. The effects on
      apoptosis and autophagy were studied by measuring caspase-3/7, Bcl-XL, Mcl-1 and
      LC3BI/II proteins. The relation between treatment response and O6-methylguanine
      DNA methyltransferase (MGMT) promoter methylation status, recurrence and gene
      expression levels of the tumors were studied. Obatoclax synergized with SAHA and
      LBH589 and sensitized cells to HDACi/RTx. Over 50% of GSC cultures were
      responsive to Obatoclax with either single agent. Combined with HDACi/RTx
      treatment, Obatoclax increased caspase-3/7 and inhibited Bcl-2 family proteins
      Bcl-XL and Mcl-1 more effectively than other treatments. Genes predictive for
      treatment response were identified, including the F-box/WD repeat-containing
      protein-7, which was previously related to Bcl-2 inhibition and HDACi
      sensitivity. We emphasize the functional relation between Bcl-2 proteins and
      radiosensitization by HDACi and provide a target for increasing responsiveness in
      glioblastoma by using the Bcl-2 inhibitor Obatoclax. 

PMID- 25568670
TI  - Taurolidine cooperates with antineoplastic drugs in neuroblastoma cells.
AB  - Neuroblastoma is the most common extracranial tumor in childhood. Outcome of
      stage 4 disease remains poor and the development of novel therapeutic approaches
      is thus urgently needed. Taurolidine (TRD), originally invented to avoid catheter
      infections, has shown to exhibit antineoplastic activity in various cancers. The
      growth of neuroblastoma cell lines is inhibited by TRD as recently demonstrated.
      Further analysis disclosed a significant negative growth effect of TRD on the
      four neuroblastoma cell lines SH-EP TET21N, SK-N-AS, SK-N-BE(2)-M17 and SK-N-SH.
      Detected IC50 (51-274 MUM; 48 h) are promising and correspond to clinically
      achievable plasma levels. Apoptosis was induced (76-86%; 48 h) in a time
      dependent manner mediated by a simultaneous activation of the intrinsic and
      extrinsic pathways. This was confirmed by cleavage of caspases -3, -8 and -9 and
      abrogation of apoptosis by pan-caspase inhibition. Application of TRD resulted in
      a significant enhancement of cytotoxic drugs vincristine/doxorubicin (2/3 of 4
      cell lines) making TRD a promising candidate to be included in neuroblastoma
      therapy regimens in the future. 

PMID- 25568671
TI  - The antihypertension drug doxazosin suppresses JAK/STATs phosphorylation and
      enhances the effects of IFN-alpha/gamma-induced apoptosis.
AB  - Doxazosin, a commonly prescribed treatment for patients with benign prostatic
      hyperplasia, serves as an alpha1-blocker of the adrenergic receptors. In this
      study, we calculated its effect on the ovarian carcinoma cells. Doxazosin induces
      dose-dependent growth suppression and is additively activated through IFN-alpha
      or IFN-gamma stimulation. They both enhanced G1 phase arrest, as well as the
      activity of caspase-3, and the reduction of cyclin D1 and CDK4 protein levels.
      Doxazosin growth suppression was abolished either by the Janus family of tyrosine
      kinase (JAK) or the signal transducer and activator of transcription (STAT)
      inhibitor treatment. The activity of JAK/STAT was dependent on the level of
      doxazosin, suggesting a requirement of doxazosin for the activation of JAK/STAT.
      Furthermore, doxazosin plus IFN-alpha or doxazosin plus IFN-gamma additively
      suppressed the activation of the JAK/STAT signals through phosphorylation of JAK
      and STAT, thus affecting the activation of subsequent downstream signaling
      components PI3K, mTOR, 70S6K, and PKCdelta. In vivo study demonstrated that
      doxazosin significantly suppressed tumor growth in an ovarian cancer cell
      xenograft mouse model, inducing apoptotic cell death by up-regulating the
      expression of p53, whereas c-Myc expression was markedly reduced. Our data
      indicate that doxazosin can modulate the apoptotic effects of IFN-alpha- and IFN
      gamma through the JAK/STAT signaling pathways. Collectively, we indicate that
      this action may be a potent chemotherapeutic property against ovarian carcinoma. 

PMID- 25568672
TI  - Closing gaps: Integrating food safety management systems into the veterinary
      curriculum a tool to improve food quality and trade.

PMID- 25568673
TI  - Ameliorative properties of aqueous extract of Ficus thonningii on erythrocyte
      osmotic fragility induced by acetaminophen in Rattus norvegicus.
AB  - In vitro antioxidant and erythrocyte protecting activities by aqueous extract of
      Ficus thonningii leaves on blood cells were studied in acetaminophen treated
      rats. The extract was safe at limit dose of 5000 mg kg(-1) body weight. The
      extract demonstrated dose dependent antihemolytic effect at dose levels between
      50 and 200 mg kg(-1) body weight. The lowest antihemolytic effect was observed at
      dose level of 200 mg kg(-1) body given the lowest percentage hemolysis of 10.53
      +/- 1.76%, whereas the highest percentage hemolysis at dose level of 50 mg kg(-1)
      was 29.02 +/- 7.45%. Hematology revealed erythrocytosis at dose levels of 100 and
      200 mg kg(-1) body weight. Hyperglobinemia and lymphocytopenia were observed at
      dose levels of 100 mg kg(-1) and 200 mg kg(-1), respectively. The extract
      effectively showed scavenging activity on a stable oxidative radical
      diphenylpicrylhydrazyl (DPPH) and a significant ferric reducing antioxidant power
      (FRAP) activity. The plausible erythrocyte membrane protective effect may be due
      to its free radical scavenging activity and hence the extract can be used to
      improve hematological parameters and ameliorate oxidative stress. 

PMID- 25568674
TI  - Adverse effects of long-time exposure to formaldehyde vapour on testicular tissue
      and sperm parameters in rats.
AB  - Formalin is widely used in industry and in medicine (as tissue fixative and
      disinfectant).It contains reactive molecules which have been known for its
      cytotoxic effects. To evaluate the effect of formalin exposure on the testicular
      tissue and sperm parameter from neonatal period through physical and sexual
      maturity, 28 male Wister rats were assigned into two equal test and control
      groups. The test group was exposed to 1.5 ppm of the vapor of 10% formaldehyde in
      a special chamber for 2 hr per day at 20-26 C and the air pressure of 760-763
      atm. After 55 days, the tubular differentiation (TDI) and repopulation (RI)
      indexes in testicular tissue, sperm quality parameters, serum total antioxidant
      capacity and testosterone level were determined. The formaldehyde-exposed animals
      showed severe seminiferous tubules atrophy, edematous connective tissue, arrested
      spermatogenesis with negative TDI and RI and vascular thrombosis compared to
      control group. Histomorphological studies showed a high sperm mortality and
      abnormality associated with a remarkable decrease in sperm count. Formaldehyde
      exposed animals revealed with decreased serum level of testosterone (p < 0.05)
      and down-regulated antioxidant status versus control group. In conclusion, the
      current data provide inclusive histological and biochemical information about the
      chronic exposure to formaldehyde with emphasizing on reproductive disorders
      including histological adverse effects on the testicular tissue, spermatogenesis,
      sperm viability, count and the abnormalities which can potentially cause
      infertility after sexual maturation. 

PMID- 25568675
TI  - Effects of dietary vitamin E on mucosal maltase and alkaline phosphatase enzyme
      activities and on the amount of mucosal malonyldialdehyde in broiler chickens.
AB  - The effects of dietary vitamin E levels on mucosal maltase and alkaline
      phosphatase (ALP) enzyme activities and on the amount of mucosal
      malonyldialdehyde (MDA) in broiler chickens were studied in the present study.
      One hundred and eighty of male day old broiler chicks (Ross 308 strain) were
      randomly assigned into five groups, each with three replicates and 12 chicks in
      each replicate. Chickens in group A were fed corn-soy- based diet, while those in
      groups B, C, D and E were fed the same diet with 20, 60, 180, and 540 mg kg(-1)
      vitamin E supplement (d-alpha tocopherol), respectively. Six birds were randomly
      chosen from each group, and were euthanized on days 10, 21, 32, and 42 of age.
      One segment of small intestine outset was homogenized and mucosal ALP and maltase
      activity were measured. Moreover, mucosal lipid peroxidate amount was measured to
      reveal the impact of vitamin E on oxidative stress. Maltase activity was
      increased with the increase of vitamin E up to 60 mg kg(-1) of diet while with
      further levels, it was decreased. Addition of 60 mg kg(-1) of vitamin E to the
      diet significantly increased ALP enzyme activity (p <= 0.001). Addition of 540 mg
      kg(-1) of vitamin E supplement to the diet led to the minimum amount of MDA at 32
      days of age. It may be concluded that supplementation of broiler's diet with 60
      mg kg(-1) of vitamin E can increase mucosal maltase and ALP enzyme activity. 

PMID- 25568676
TI  - PCR detection of Campylobacter fetus subspecies venerealis in smegma samples
      collected from dairy cattle in Fars, Iran.
AB  - Bovine venereal campylobacteriosis, caused by Campylobacter fetus subsp.
      venerealis (Cfv), is regarded as one of the major threats to the cattle industry
      around the world. Abortion and infertility are two important reproductive
      problems in cows infected with C. fetus subsp. venerealis. Reports on the
      presence of Cfv are scarce in the cattle, in Iran. Therefore, the present study
      was designed to examine the presence of Cfv in the reproductive tract of dairy
      cattle either slaughtered in Shiraz abattoir or dairy herds with a history of
      infertility and abortion, and further to identify and differentiate this micro
      organism in dairy cattle in Fars, south of Iran. A total of 95 smegma samples
      from the preputial cavity and the fornix of the cervical opening were collected
      using scraping method from bulls (n = 34) and cows (n = 61) in addition to eight
      samples of commercially bull frozen semen. Smegma samples were then cultured for
      isolation of Cfv and then the extracted DNA was examined for the presence of Cfv
      using an optimized multiplex PCR assay. None of the frozen semen samples examined
      were positive for Cfv. However, out of 95 smegma samples, thirteen animals
      (12.6%) were found positive for Cfv consisting of 3 males and 10 females. In
      conclusion, the results of the current study clearly confirmed the presence of
      Cfv using PCR in the slaughtered cattle and dairy farms with a history of poor
      fertility and abortion in Fars, Iran. 

PMID- 25568677
TI  - Effects of flunixin meglumine on experimental tendon wound healing: A
      histopathological and mechanical study in rabbits.
AB  - Tendons are frequently targets of injury in sports and work. Whether nonsteroidal
      anti-inflammatory drugs (NSAIDs) have beneficial effects on tendon healing is
      still a matter of debate. This study was conducted to evaluate effects of
      flunixin meglumine (FM) on tendon healing after experimentally induced acute
      trauma. Twenty eight adult male New Zealand White rabbits were subjected to
      complete transection of deep digital flexor tendons followed by suture placement.
      Treatment group received intramuscular injection of FM for three days, and
      controls received placebo. Subsequently, cast immobilization was continued for
      two weeks. Animals were sacrificed four weeks after surgery and tissue samples
      were taken. The histological evaluations revealed improved structural
      characteristics of neotendon formation including fibrillar linearity, fibrillar
      continuity and neovascularization in treatment group compared to those of
      controls (p < 0.05). However, no significant differences were found between two
      groups in terms of epitenon thickness (p > 0.05). Mechanical evaluation revealed
      significant increase in load-related material properties including ultimate load,
      yield load, energy absorption and ultimate stress in treatment group compared to
      those of control group (p < 0.05). However, no statistically significant
      differences in terms of stiffness and ultimate strain were found (p > 0.05). The
      present study showed that intramuscular injection of FM resulted in improved
      structural and mechanical properties of tendon repairs and it could be an
      effective treatment for acute tendon injuries like severance and laceration. 

PMID- 25568678
TI  - Serum concentrations of thyroid hormones, cholesterol and triglyceride, and their
      correlations together in clinically healthy camels (Camelus dromedarius): Effects
      of season, sex and age.
AB  - To evaluate the effects of season, sex and age on serum concentrations of thyroid
      hormones, cholesterol and triglyceride, and their correlations together in
      dromedarian camels, these parameters were measured in 180 clinically healthy
      dromedary camels. No significant difference was detected for the measured serum
      parameters between the two sexes and among the different age groups of camels and
      none of them had significant correlation with the age of the animals. There was a
      significant correlation between serum T4 and triglyceride (r = -0.243, p =
      0.002). There were significant differences between summer and winter seasons in
      the serum concentrations of T4 (p < 0.001), T3 (p = 0.01) and triglyceride (p <
      0.001). In winter, the serum concentration of triglyceride had a significant
      correlation with the age of the sampled camels (r = -0.235, p = 0.026). In male
      camels,T4 had a marginally significant correlation with cholesterol (r= -0.158, p
      = 0.06).The effects of season, sex and age on the serum concentrations and
      relationships between thyroid hormones, cholesterol and triglyceride in dromedary
      camels can be proposed as the probable causes of the controversial findings in
      the previous studies. 

PMID- 25568679
TI  - Evaluation of hooves' morphometric parameters in different hoof trimming times in
      dairy cows.
AB  - Wide variety of timings and techniques has been used based on the housing,
      production, availability of requirements etc. This current study was done for a
      morphologic evaluation of the cow's digit in different trimming times. A dairy
      herd with 2200 milking cow, free stalls barns, average daily production of 36
      liters per cow was selected. Forty cows were assigned to four groups based on
      hoof trimming times as, 100-120 days in milk (Group I), cows before drying (Group
      II), visual long toed cows (Group III) and delayed pregnant cows (Group IV). Toe
      length from coronary band to the toe tip (A), dorsal hoof angle (D), toe height
      from coronary band in toe region to the ground level (B), heel height from
      coronary band in heel region to the ground level (C) and heel height to toe
      length proportion was measured. The highest toe length was recorded in medial
      digit of group IV (9.19 +/- 0.68 cm) and the lowest one recorded in lateral digit
      of group I (8.28 +/- 0.62 cm). Distribution of the cows in different groups under
      study was based on their toe length, as the highest and lowest distribution were
      recorded in groups III and I, respectively. The highest measurements in all
      indices were recorded in group IV that followed by group III except for toe
      height that was higher in group II following group IV. The lowest toe length was
      recorded in group I that needs more attention due to the risk of over trimming
      and its supposed complications in this group. 

PMID- 25568680
TI  - Protective effects of garlic aquous extract (Allium sativum), vitamin E, and N
      acetylcysteine on reproductive quality of male rats exposed to lead.
AB  - The objective of present study was to investigate the effects of aqueous garlic
      extracts, vitamin E and N-acetylcysteine on lead-induced lipid peroxidation,
      changes in antioxidant defense system and semen quality in the rat testes. Twenty
      five male rats were divided into five groups. Animals within different treatment
      groups were maintained on their respective diets for 35 days as follows: group 1
      rats served as control and received water and standard pellets as food ad
      libitum; group 2 received lead acetate by gavage (1000 ppm); group 3 was treated
      with A. sativum extract (400 mg kg(-1), by gavage) plus lead acetate (1000 ppm);
      group 4 was treated orally with vitamin E (300 mg of alpha-tocopherol per kg of
      chow) plus lead acetate (1000 ppm); group 5 was treated orally with N
      acetylcysteine (800 ppm)plus lead acetate (1000 ppm). The weights of testes,
      epididymis, epididymal sperm count, viable and motile sperms decreased
      significantly (p < 0.05) in lead-exposed rats. However treatment with vitamin E
      and aqueous garlic extract resulted in a significant (p < 0.05) increase in sperm
      motility and viability. Exposure to lead acetate significantly increased
      malondialdehyde (MDA) level with a significant decrease in the superoxide
      dismutase (SOD) activities in the testes of rats while co-administration of
      vitamin E and lead caused a significant (p < 0.05) decrease in MDA concentration
      compared with lead-exposed group. These results suggest that both vitamin E and
      in to a lesser extent aqueous garlic extract have a potent antioxidant protection
      in the testes of rat against the lead-induced oxidative stress. 

PMID- 25568681
TI  - Effect of gibberellic acid on the quality of sperm and in vitro fertilization
      outcome in adult male rats.
AB  - Gibberellic acid (GA3) is a group of plant hormones identified in various plants.
      The aim of this study was to determine the effects of GA3 on sperm parameters and
      in vitro fertilization (IVF). Fifty six adult male rats were divided into seven
      groups as, control, treatment and sham. Following 15, 30 and 45 days of GA3 and
      methanol alcohol (MA) administration, rats were euthanized and epididymis tail
      was transferred to human tubular fluid (HTF) medium containing 4 mg mL(-1) bovine
      serum albumin (BSA) .Total number of sperms, the percentage of live sperms,
      immature sperms and sperms with damaged chromatin and IVF were examined. The
      oocytes were obtained from immature rats after the injection of pregnant mare's
      serum (PMSG) and human chorionic gonadotropin (HCG) hormones. Human tubular fluid
      was used as the fertilization medium and zygotes transferred to fresh 1-cell rat
      embryos culture medium (mR1ECM) to reach the blastocyst stage. This study showed
      that GA3 could decrease the number of total sperms on days 30 and 45 in treated
      group comparison with the control and sham groups. Additionally, GA3 increased
      the immature sperms and sperms with damaged chromatin. The percentage of
      fertilization, two-cell embryos and blastocyst resulting from the treatment group
      on days 30 and 45 also decreased and showed significant differences with the
      control and sham groups (p < 0.05). The results obtained from this study
      indicated that the oral use of GA3 could reduce the fertility in rats by
      influencing the sperm number and the quality of sperm's chromatins. 

PMID- 25568682
TI  - No mutations of FecB and FecG(H) in Iranian Lory sheep.
AB  - The Booroola fecundity gene (FecB) and growth differentiation factor 9 (GDF9)
      gene belong to the transforming growth factor beta (TGF-beta) superfamily. The
      mutations of these genes have additive effects on the prolificacy in sheep. The
      aim of the present study was to determine the possible mutations of FecB and
      FecG(H) genes in Lory sheep breed of the Lorestan province, Iran. Sixty blood
      samples were collected and DNA was extracted from whole fresh blood. For
      detection of FecB and FecG(H) mutations, the PCR products were incubated with
      AvaII and DdeI restricted enzymes. Based on the results we did not find the FecB
      and FecG(H) mutations in this sheep breed population, so these mutations cannot
      the cause of the high prolificacy of Lory sheep breed and more study are needed
      to determine the genetic or environmental causes of high prolificacy of this
      sheep breed. 

PMID- 25568683
TI  - Biofilm formation, hemolysin production and antimicrobial susceptibilities of
      Streptococcus agalactiae isolated from the mastitis milk of dairy cows in
      Shahrekord district, Iran.
AB  - Streptococcus agalactiae is a major contagious pathogen causing bovine sub
      clinical mastitis. The present investigation was carried out to determine some
      phenotypic characteristics of the S. agalactiae strains isolated from bovine
      mastitis cases in dairy cows of Shahrekord in the west-center of Iran. One
      hundred eighty California mastitis test (CMT) positive milk samples were
      bacteriologically studied. A total of 31 (17.2%) S. agalactiae isolated. Twenty
      eight (90.3%) of the isolates were biofilm producers. This finding may indicate
      the high potential of pathogenicity in isolated strains. Sixteen (51.6%) isolates
      were alpha hemolysin producers. Only 19.3%, 22.5% and 29.0% of the isolates were
      sensitive to streptomycin, flumequine and kanamycin, respectively. None of these
      three agents is recommended for treatment of mastitis cases. 

PMID- 25568684
TI  - Trypanosomiasis of camels (Camelus dromedarius) in Algeria: First report.
AB  - Camel trypanosomosis is a life-threatening disease in the camel species and
      responsible for severe economic losses either in milk or meat productions. This
      study was carried out on the south-east area of Algeria on 100 camels of various
      ages and either sex from two herds. Microscopic examination of blood smears
      revealed higher levels of trypanosomosis caused by Trypanosoma evansi, an
      elongated parasite with a kinetoplast and a single nucleus located in its half
      length and one flagellum with great heterogeneity. This first investigation
      reveals higher infection rate than those observed in other countries using blood
      smears, the trypanosomosis attack has reached an alarming level and the
      occurrence of trypanosomosis at this high level on blood smears is like "the tree
      that hides the forest" and make up a serious and potential danger both on animal
      and public health. Therefore, radical preventive and offensive drastic measures
      must be taken against this menacing disease at the critical points to prevent the
      economic losses and to avoid possible human transmission. 

PMID- 25568685
TI  - Frequency of cardiac arrhythmias in high- and low- yielding dairy cows.
AB  - Electrocardiography (ECG) may be used to recognize cardiac disorders. Levels of
      milk production may change the serum electrolytes which its imbalance has a role
      in cardiac arrhythmia. Fifty high yielding and fifty low yielding Holstein dairy
      cows were used in this study. Electrocardiography was recorded by base-apex lead
      and blood samples were collected from jugular vein for measurement of serum
      elements such as sodium, potassium, calcium, phosphorous, iron and magnesium.
      Cardiac dysrhythmias were detected more frequent in low yielding Holstein cows
      (62.00%) compared to high yielding Holstein cows (46.00%). The cardiac
      dysrhythmias that were observed in low yielding Holstein cows included sinus
      arrhythmia (34.70%), wandering pacemaker (22.45 %), bradycardia (18.37%),
      tachycardia (10.20%), atrial premature beat (2.04%), sinoatrial block (2.04%),
      atrial fibrillation (8.16%) and atrial tachycardia (2.04%). The cardiac
      dysrhythmias were observed in high yielding Holstein cows including, sinus
      arrhythmia (86.95%) and wandering pacemaker (13.05%). Also, notched P wave was
      observed to be 30% and 14% in high- and low- yielding Holstein cows respectively.
      The serum calcium concentration of low yielding Holstein cows was significantly
      lower than that of high yielding Holstein cows. There was not any detectable
      significant difference in other serum elements between high- and low- yielding
      Holstein cows. Based on the result of present study, could be concluded that low
      serum concentration of calcium results to more frequent dysrhythmias in low
      yielding Holstein cows. 

PMID- 25568686
TI  - Interrelationship of betaeta-2 microglobulin, blood urea nitrogen and creatinine
      in streptozotocin-induced diabetes mellitus in rabbits.
AB  - Measurement of serum creatinine (Cr) and blood urea nitrogen (BUN) are used as
      indicators of glomerular filtration rate. The increased levels of these
      biomarkers are usually detectable at advanced stages of kidney complications. The
      aim of this study was to find the interrelationship of beta-2 microglobulin
      (beta2M), BUN and Cr in streptozotocin (STZ)-induced diabetes mellitus in
      rabbits. Diabetes was induced by a single intraperitoneal (IP) injection of 65 mg
      kg(-1) of STZ in rabbits. The levels of serum insulin, glucose and three above
      mentioned biomarkers were measured one day before (day -1) and on days 1-3 after
      injection of STZ and continued weekly to the end of the experiment (12 weeks). A
      statistically significant increase of serum beta2M, BUN, Cr and glucose levels,
      and a significant decrease of insulin levels were observed in diabetic animals.
      However, beta2M levels increased as early as one day after STZ injection compared
      to Cr and BUN that elevated at day two, suggesting a probable diagnostic
      advantage of beta2M over currently used biomarkers in diabetic related kidney
      complications. 

PMID- 25568687
TI  - Relationship between season, lactation number and incidence of clinical mastitis
      in different stages of lactation in a Holstein dairy farm.
AB  - The aim of the present study was to compare the occurrence and duration of
      clinical mastitis in different seasons, stages of lactation period and parities
      in a Holstein dairy farm in Iran. A retrospective epidemiological survey from
      April 2005 to March 2008 was conducted on 884 clinical mastitis cases of 7437
      lactations. Data of each case including calendar-date of mastitis onset, days in
      milk (DIM) of mastitis onset (early: 0-74 DIM; middle: 75-150 DIM, and late >=
      150 DIM), duration of mastitis, and parity (1, 2, and >= 3) were recorded. Based
      on date of mastitis onset, cases were classified into stages of lactation.
      Moreover, beginning of mastitis was seasonally categorized. Duration of clinical
      mastitis after treatment in early lactation was less than late lactation in the
      first-parity cows (p = 0.005). In early lactation period, the first-parity cows
      suffered clinical mastitis in days earlier than two other parity groups (p <
      0.001). Moreover, in late lactation period, the first-parity cows had clinical
      mastitis in days later than cows in the third and more parities (p = 0.002).
      Occurrence of clinical mastitis in summer increased in late lactation period but
      in winter increased in early lactation period (p = 0.001). In addition,
      occurrence time of clinical mastitis in summer were in days later than in spring
      (p = 0.02) and winter (p = 0.03) in early lactation period. In conclusion,
      occurrence of mastitis in winter and spring during early lactation and in summer
      during late lactation period were more prevalent especially in lower parities. 

PMID- 25568688
TI  - Protective effects of vitamin E and Cornus mas fruit extract on methotrexate
      induced cytotoxicity in sperms of adult mice.
AB  - This study was aimed to assess the protective effects of Cornus mas fruit extract
      (CMFE) and vitamin E (Vit E) on sperm quality parameters in the methotrexate
      (MTX)-treated mice. Forty-eight young adult male mice (8-12 weeks) were randomly
      divided into six groups including control and test groups. The control group
      received normal saline orally , and the test groups were treated MTX (20 mg kg(
      1), ip, once weekly), MTX + CMFE (250 mg kg(-1)), MTX + CMFE (500 mg kg(-1)), MTX
      + CMFE (1000 mg kg(-1)), and MTX + Vit E (100 IU kg(-1), po) for 35 consecutive
      days. On day 35, after euthanasia the epididymal sperms were isolated. Then the
      total mean sperm count, sperm viability and motility were determined. The total
      antioxidant capacity (TAOC) of all experimental groups were also evaluated. The
      MTX-treated animals showed a significant changes in all parameters of sperm
      quality assessment compared to the control group. Both Vit E and CMFE were able
      to protect from MTX-induced effects on sperm maturity and DNA damage. Co
      administration of MTX and CMFE and/or Vit E resulted in protection from MTX
      reduced TAOC. In conclusion, these data suggested that MTX administration could
      adversely affect the sperm quality. Moreover, the protective effect of Vit E and
      CMFE on MTX-induced sperm toxicity was also documented. 

PMID- 25568689
TI  - Molecular characterization and antibiotic resistance of enterotoxigenic and
      entero-aggregative Escherichia coli isolated from raw milk and unpasteurized
      cheeses.
AB  - The aim of this study was to determine the occurrence of enterotoxigenic and
      enteroaggregative Escherichia coli strains and antibiotic resistance of the
      isolates in raw milk and unpasteurized cheese. Out of 200 samples of raw milk and
      50 samples of unpasteurized cheeses, 96 and 24 strains of E. coli were isolated,
      respectively. Polymerase chain reaction (PCR) was used to detect the genes
      encoding heat-stable enterotoxin a (STa), heat-stable enterotoxin b (STb), heat
      labile toxin (LT) and enteroaggregative heat-stable toxin1 (EAST1). Twelve out of
      120 (10.00%) isolates harbored the gene for EAST1, 2(1.66%) isolates were
      detected as producing STb and LT toxins and 12 (10.00%) strains contained STb and
      EAST1 genes. None of the strains contain the STa gene. All of the strains were
      tested for antibiotic resistance by disk diffusion method. Disks included:
      ciprofloxacin (CFN), trimetoprim-sulfamethoxazole (TSX), oxytetracycline (OTC),
      gentamicin (GMN), cephalexin (CPN), nalidixic acid (NDA) and nitrofurantoin
      (NFN), ampicillin (AMP), neomycin (NEO) and streptomycin (STM). Among 120
      isolated strains of E. coli, the resistance to each antibiotics were as follows:
      OTC100%, CPN 86.00%, NDA 56.00%, NFN 42.00%, GMN 30.00%, TSX 28.00%, CFN 20%, AM
      23.40% and STM 4.25%. None of the isolates were resistant to NEO. The present
      data indicate that different resistant E. coli pathogens may be found in raw milk
      and unpasteurized cheese. It poses an infection risk for human and transferring
      the resistant factors to microflora of the consumers gut. 

PMID- 25568690
TI  - The effects of short term intravenous infusion of a soybean based lipid emulsion
      on some blood constituents in sheep: A preliminary study.
AB  - To evaluate the effect of intravenous infusion of a soybean based lipid emulsion
      (Lipovenoes 10%) on some blood constituents in sheep, a replicated 2 * 2 Latin
      square design experiment was conducted in four clinically healthy ewes. Lipid
      emulsion (LE group) or normal saline (NS group) was infused intravenously at a
      rate of 0.025 mL kg(-1) per min for 6 hr and the concentrations of blood
      triglyceride, glucose, insulin, calcium, magnesium, phosphorous, sodium and
      potassium were measured before (baseline) and then at timepoints 2, 4, 6, 12 and
      24 hr after infusion. Compared to the baseline values and/or NS infusion, LE
      infusion resulted in a significant increase in the concentrations of triglyceride
      (p < 0.001), glucose (p < 0.01), calcium (p < 0.05), phosphorous (p < 0.01) and a
      significant decrease in insulin (p < 0.001) and magnesium (p < 0.05)
      concentrations. Compared to the baseline value, the homeostasis model of insulin
      resistance (HOMA-IR) index increased (p < 0.001) at timepoints 2 and 4 hr and
      abruptly decreased at timepoint six hr (p < 0.01) following LE infusion. In LE
      group, HOMA-IR values were significantly (p < 0.001) higher than those for NS
      group at timepoints 2 and 4 hr after infusion. Neither treatment nor time
      influenced serum sodium and potassium concentrations (p > 0.05). In conclusion,
      intravenous infusion of Lipovenoes temporarily influenced some blood
      constituents. Increased triglyceride concentrations were associated with an
      increase in HOMA-IR values indicating a state of insulin resistance. No
      remarkable adverse effect was observed following LE infusion and lipid based
      emulsions can be safely used in ruminants not suffering from extensive lipid
      mobilization. 

PMID- 25568691
TI  - Chemical composition and the nutritive value of pistachio epicarp (in situ
      degradation and in vitro gas production techniques).
AB  - The nutritive value of pistachio epicarp (PE) was evaluated by in situ and in
      vitro techniques. Chemical analysis indicated that PE was high in crude protein
      (11.30%) and low in neutral detergent fiber (26.20%). Total phenols, total
      tannins, condensed tannins and hydrolysable tannins contents in PE were 8.29%,
      4.48%, 0.49% and 3.79%, respectively. Ruminal dry matter and crude protein
      degradation after 48 hr incubation were 75.21% and 82.52%, respectively. The gas
      production volume at 48 hr for PE was 122.47 mL g(-1)DM. As a whole, adding
      polyethylene glycol (PEG) to PE increased (p < 0.05) gas production volumes,
      organic matter digestibility and the metabolizable energy that illustrated
      inhibitory effect of phenolics on rumen microbial fermentation and the positive
      influence of PEG on digestion PE. The results showed that PE possessed potentials
      to being used as feed supplements. 

PMID- 25568692
TI  - Role of opioid system in verapamil-induced antinociception in a rat model of
      orofacial pain.
AB  - Calcium, through its various channels involves in local, spinal and supra-spinal
      transmission of pain. In the present study, we investigated the separate and
      combined treatment effects of verapamil (a calcium channel blocker), morphine (an
      opioid agonist) and naloxone (an opioid antagonist) on pain in the orofacial
      region of rats. Orofacial pain was induced by subcutaneous (SC) injection of
      formalin (50 uL, 1.5%) into the left upper lip side, and the time durations spent
      face rubbing with epsilateral forepaw were recorded in three min blocks for a
      period of 45 min. Formalin induced a biphasic pattern (first phase: 0-3 min;
      second phase: 15-33 min) of pain. Intraperitoneal (IP) injections of verapamil (2
      and 8 mg kg(-1)) and morphine (2 and 4 mg kg(-1)) suppressed orofacial pain. Co
      administration of sub-analgesic doses of verapamil (0.5 mg kg(-1)) and morphine
      (1 mg kg(-1)) produced second phase analgesia. Both phases of formalin-induced
      pain were suppressed when an analgesic dose (2 mg kg(-1)) of verapamil co
      administered with a sub-analgesic dose (1 mg kg(-1)) of morphine. The SC
      injection of naloxone (2 mg kg(-1)) alone with no effect on pain intensity,
      prevented the antinociceptive effects induced by morphine (2 mg kg(-1)), but not
      verapamil (2 mg kg(-1)). The obtained results showed antinociceptive effects for
      verapamli and morphine on orofacial pain. Co-administrations of verapamil and
      morphine produced antinociceptive effects. It seems that opioid analgesic system
      may not have a role in the verapamil-induced antinociception. 

PMID- 25568693
TI  - Cryptosporidium parvum and Cryptosporidium andersoni infection in naturally
      infected cattle of northwest Iran.
AB  - The protozoan intestinal parasite Cryptosporidium commonly infects cattle
      throughout the world and Iran. The present study was undertaken to determine the
      abundance and associated risk factors of Cryptosporidium infection in cattle
      herds of northwestern Iran. A total number of 246 fecal samples from 138 (56.1%)
      diarrheic (D) and 108 (43.9%) non-diarrheic (ND) cattle were randomly collected
      and examined by fecal smears stained with Ziehl-Neelsen. For molecular
      specification, DNA was extracted from collected Cryptosporidium oocysts and a
      fragment of 1325 bp in size from 18S rRNA gene was amplified. The overall
      prevalence of Cryptosporidium infection was 22.3% (55/246). The prevalence of
      Cryptosporidium infection in examined calves less than 6 month-old was
      significantly higher than adult cattle. C. parvum and C. andersoni were
      identified in 20.3% (50/246) and 2.03% (5/246) of examined cattle, respectively.
      The highest prevalence of C. parvum infection was found in D calves < 6 month-old
      (13.4%, 33/246), while C. andersoni was only detected in ND cattle (8.9%,
      22/246). There was significant difference in the prevalence between male than
      female cattle. There was no significant difference between prevalence and seasons
      of investigation. It was concluded that C. parvum was the prevalent species in
      younger animals compared to older ones as a potentially zoonotic agent in the
      region. 

PMID- 25568694
TI  - Study on mange mite of camel in Raya-Azebo district, northern Ethiopia.
AB  - A cross-sectional study was carried out to determine the prevalence and species
      of camel mange mite infestation in Raya-Azebo district, Northern part of
      Ethiopia. Accordingly, Three hundred and eighty-four camels were examined and
      mange mite infestation was detected on 64 of camels. Only Sarcoptes scabiei var.
      cameli was identified as the only mite species in all skin scraping samples
      collected from the suspected mange mite lesions. There was significant difference
      in the prevalence of mange mite infestation between male and female camels (p <
      0.05) but no significance difference was observed among the age groups and body
      condition score of camels (p > 0.05). The result indicated that camel mange mite
      infestation was a problem in northern part of Ethiopia, hence, further studies
      and strategic control measures are recommended to reduce the effect of mange mite
      infestation on camel husbandry. 

PMID- 25568696
TI  - Seroprevalence of Neospora caninum in slaughtered native cattle in Kurdistan
      province, Iran.
AB  - Neospora caninum is a worldwide distributed pathogen which causes abortion in
      cattle leading to economic loss in the cattle industry. The aim of this study was
      to determine the seroprevalence of N. caninum antibodies in the native cattle
      slaughtered in various areas of Kurdistan province (western Iran) from September
      2010 to September 2011. Serum samples from 368 cattle slaughtered in seven
      slaughterhouses in this region were taken for detection of anti-N. caninum
      antibodies using commercial N. caninum ELISA kit. Antibodies to N. caninum were
      found in 29 samples (7.80%). The present study was the first report of Neospora
      infection in this region and indicated that native cattle of Kurdistan province
      were exposed to this parasite. 

PMID- 25568695
TI  - Prevalence and risk factors for Salmonella spp. colonization in broiler flocks in
      Shiraz, southern Iran.
AB  - Salmonella spp. are important food borne pathogens worldwide that frequently
      infect poultry flocks. This cross-sectional study was conducted to determine the
      prevalence of Salmonella spp. colonization in broiler flocks in Shiraz (southern
      Iran) and to find the possible association of infection status with some
      potential risk factors including vaccination program and use of antibiotics.
      During October 2009 to April 2010, a total of 40 broiler flocks were selected in
      slaughterhouse and 20 cloacae contents were collected from each flock. Every five
      cloacae contents were pooled and investigated for Salmonella spp. using
      appropriate culture methods. The flock was considered positive if any of the
      pooled samples turned positive in culture. Statistical analysis was performed
      using multiple logistic regression. Nine out of 40 flocks (22.50%, 95% CI: 9-36)
      were positive for Salmonella spp. colonization. Nearly 75.00% of flock owners
      reported that they used antibiotics during production period, more frequently
      fluoroquinolones, combination of trimethoprim-sulfonamides (TMP/SU) and
      tetracycline. Nearly 60.00% of the flocks which had used TMP/SU were positive for
      Salmonella spp. compared with 10.00% of the flocks which did not use this
      antibiotic (p = 0.006). Increasing flock age was associated with a decreased
      chance of Salmonella spp. detection (p = 0.003). In flocks which received
      infectious bronchitis vaccine, 36.00% were positive for Salmonella spp. whereas
      this was 15.00% for flocks which did not receive this vaccine (p = 0.08). Careful
      monitoring of antibiotics use and further studies to determine the most
      appropriate vaccination program in the field is recommended. 

PMID- 25568697
TI  - A case of conjoined twins (thoraco-omphalopygopagus tribrachius tetrapus) in
      lamb.
AB  - Nearly completed conjoined or fused symmetrical twins are generally called
      diplopagus. Sheep conjoined twins have been reported less than cow. An apparently
      female conjoined twin lambs was examined based on external and internal features.
      In radiology, two vertebral columns and two pairs of the ribs were seen. Only two
      heads and two necks were separated (thoraco-omphalopygopagus). There were three
      forelimbs (tribrachius), one of which grew on dorsal region as a notomelus. Teat
      buds of the monsters differed in number. Only one lamb had umbilicus, including
      one umbilical vein, and two umbilical arteries locating besides one urinary
      bladder. This lamb had also one uterus. Two-separated alimentary tracts were
      observed in a common abdomen. Common thorax and abdominal cavities were separated
      by a diaphragm. There were two esophageal hiatuses, and two caval foramina but
      only one aortic hiatus. Two pairs of lungs and two unequal and connected hearts
      in a common pericardium were observed. Abnormality of the circulatory system
      might have caused the death of the twins. 

PMID- 25568698
TI  - Spiculopteragia asymmetrica infection in Cervus elaphus from Iran.
AB  - Spiculopteragia asymmetrica is a gastrointestinal nematode frequently found in
      the abomasum of cervids. During December and February 2010, two red deer were
      died in Semeskandeh sanctuary in Mazandaran province. Moreover, five live deer
      from mentioned area were treated by Ivermectin and collected feces of these
      animals were used for assessment helminthes infection by parasitological methods.
      Several nematodes were recovered in abomasums and in fecal samples of treated
      animals. Number of worms recovered from abomasums of two dead animals were 275
      (90 male and 185 female) from the first one and 327 (102 male and 225 female)
      from the second. Based on morphological characteristics nematodes were diagnosed
      as S . asymmetrica. This is the first report of existence of S . asymmetrica from
      cervids in Iran. 

PMID- 25568699
TI  - Bio-efficacy comparison of herbal-methionine and DL-methionine based on
      performance and blood parameters of broiler chickens.
AB  - This study was conducted to compare the bio-efficacy of herbal methionine (H-Met)
      relative to DL-methionine (DL-Met) on 160 "Ross 308" broiler chickens. DL-Met and
      H-Met were added to the basal diet in eight experimental treatments with three
      and four concentrations respectively in starter, grower and finisher period.
      Blood parameters which were measured at 24 and 42 days of age consisted of: serum
      proteins (total protein, albumin and globulin), serum uric acid, serum fats (low
      density lipoprotein, high density lipoprotein, triglyceride and cholesterol) and
      serum enzymes (alanine amino transaminase and aspartate amino transaminase).
      Completely randomized design, multi-exponential and multilinear regressions were
      used to determine bio-efficacy of H-Met in terms of performance and blood
      parameters of broilers. The results showed that supplemented methionine (Met)
      sources had no significant effect on blood parameters at 24 day of age. At 42 day
      of age the amounts of globulin and serum high density lipoprotein (HDL) increased
      with supplemented Met, (p < 0.05). Regression analysis revealed that H-Met was
      55.00, 71.00, 78.00, 47.00, 58.00 and 73.00% as efficacious as DL-Met for body
      weight gain, feed intake, feed conversion ratio, albumin, globulin and high
      density lipoprotein criteria, respectively. The average of bio-efficacy of H-Met
      compared to DL-Met was 67.00% and 59.00% on average across performance criteria
      and blood criteria respectively and was 63.00% across these two criteria tested.
      The results of the present study indicated that H-Met can be administered as a
      new and a natural source of Met in poultry industry. 

PMID- 25568700
TI  - Effect of carboxymethyl cellulose edible coating containing Zataria multiflora
      essential oil and grape seed extract on chemical attributes of rainbow trout
      meat.
AB  - Meat products, especially fish meat, are very susceptible to lipid oxidation and
      microbial spoilage. In this study, first, gas chromatography mass spectrometry
      (GC-MS) analysis of Zataria multiflora essential oil (ZEO) components was done
      and then two concentrations of ZEO, (1% and 2%) and two concentrations of grape
      seed extract (GSE), (0.5% and 1%) were used in carboxymethyl cellulose coating
      alone and in combination, and their antioxidant effects on rainbow trout meat
      were evaluated in a 20-day period using thiobarbituric acid reactive substances
      (TBARS) test. Their effects on total volatile basic nitrogen (TVBN) and pH were
      evaluated as well. The main components of ZEO are thymol and carvacrol. These
      components significantly decreased production of thiobarbituric acid (TBA), TVBN
      and pH level of fish meat. The initial pH, TVBN and TBA content was 6.62, 12.67
      mg N per 100 g and 0.19 mg kg(-1), respectively. In most treatments significant
      (p < 0.05) effects on aforementioned factors was seen during storage at 4 C. The
      results indicated that use of ZEO and GSE as a natural antioxidant agents was
      effective in reducing undesirable chemical reactions in storage of fish meat. 

PMID- 25568702
TI  - Effects of diluting medium and holding time on sperm motility analysis by CASA in
      ram.
AB  - The aim of this study was to evaluate the effects of dilution rate and holding
      time on various motility parameters using computer-assisted sperm analysis
      (CASA). The semen samples were collected from three Ghezel rams. Samples were
      diluted in seminal plasma (SP), phosphate-buffered saline (PBS) containing 1%
      bovine serum albumin (BSA) and Bioexcell. The motility parameters that computed
      and recorded by CASA include curvilinear velocity (VCL), straight line velocity
      (VSL), average path velocity (VAP), straightness (STR), linearity (LIN),
      amplitude of lateral head displacement (ALH), and beat cross frequency (BCF). In
      all diluters, there was a decrease in the average of all three parameters of
      sperms movement velocity as the time passed, but density of this decrease was
      more intensive in SP. The average of ALH between diluters indicated a significant
      difference, as it was more in Bioexcell in comparison with the similar amount in
      SP and PBS. The average of LIN in the diluted sperms in Bioexcell was less than
      two other diluters in all three times. The motility parameters of the diluted
      sperms in Bioexcell and PBS indicated an important and considerable difference
      with the diluted sperms in SP. According to the gained results, the Bioexcell has
      greater ability in preserving motility of sperm in comparison with the other
      diluters but as SP is considered as physiological environment for sperm. It seems
      that the evaluation of the motility parameters in Bioexcell and PBS cannot be an
      accurate and comparable evaluation with SP. 

PMID- 25568701
TI  - Preliminary phytochemical and elemental analysis of aqueous and fractionated pod
      extracts of Acacia nilotica (Thorn mimosa).
AB  - Acacia nilotica (Thorn mimosa) is used locally for various medicinal purposes by
      traditionalists and herbalists in northeastern Nigeria. Plants products have been
      used since ancient times in the management of various conditions. The bark of A.
      nilotica has been reported to be used traditionally to manage diabetes,
      dysentery, leprosy, ulcers, cancers, tumor of the eye, ear and testicles,
      induration of liver and spleen and also in treatment of various condylomas. The
      objective of this study is to determine the phytochemical and elemental
      constituents of the extracts of A. nilotica pods. Flame emission and atomic
      absorption spectrometry were also used to determine the presence or absence of
      micro- and macro-elements in the extracts. Phytochemical analysis of the aqueous,
      ethyl acetate and N-butanol fractionated portions of the pod extracts of A.
      nilotica revealed the presence of tannins, saponins, flavonoids, carbohydrate,
      whereas carbohydrates and tannins were the only constituent in the residue
      portion. Anthraquinones, alkaloids, terpene and steroids were not present in the
      extracts. The elemental screening revealed the presence of iron, potassium,
      manganese, zinc, calcium, phosphorous, magnesium, sodium, cadmium and copper.
      Lead, arsenic and molybdenum were not detected in the pod. 

PMID- 25568703
TI  - Modeling the growth of Staphylococcus aureus as affected by black zira (Bunium
      persicum) essential oil, temperature, pH and inoculum levels.
AB  - Black zira (Bunium persicum) is a medicinal plant and spice, naturally grows in
      Iran. The aim of this study was to investigate the combined effects of different
      concentrations of Bunium persicum essential oil (EO; including 0, 0.08, 0.16 and
      0.24%), three incubation temperatures (15, 25 and 35C), three levels of pH (5, 6
      and 7 adjusted by hydrochloric acid), and three inoculum size (10(2), 10(3) and
      10(4) CFU mL(-1)) on the growth of Staphylococcus aureus in the brain heart
      infusion broth. Black zira EO was extracted and its component was identified
      using gas chromatography-mass spectrometry (GC-MS) analyses. The experiment was
      carried out in triplicate. Growth was monitored by visible turbidity during a 30
      day period. To evaluate effects of explanatory variable on time to detection
      (TTD) of bacterial growth, parametric survival models based on Log-normal
      distribution was used. All explanatory variables had significant association with
      time to detection (p < 0.05). The final model accurately predicted the growth
      initiation and inhibition of S. aureus. 

PMID- 25568704
TI  - A study on the effects of the estrous cycle on uterine fluid and blood serum
      immunoglobulin G (IgG) content in the cow.
AB  - To investigate the IgG content and its variations in uterine fluid (UF) during
      the estrous cycle of the cow and to compare them with those of the blood serum
      (S), six pairs of serum and UF samples for each phase of the cycle selected out
      of 240 bovine genital tracts and blood samples were collected from Urmia
      abattoir. The UF samples were collected by gentle scraping of the endometrium
      using a curette after uterine incision and their IgG content and those of the
      serum were measured by single radial immuno-diffusion (SRID) assay. Serum IgG
      values (Mean +/- SEM) were generally higher than the UF values throughout the
      cycle except for di-estrus (S: 38.50 +/- 0.90, UF: 51.60 +/- 2.10 mg mL(-1)), in
      which the highest values were observed in UF samples. In met-estrus the
      difference was not significant (S: 34.80 +/- 1.80 mg mL(-1), UF: 30.80 +/- 5.20
      mg mL(-1)), however, in estrus the mean UF IgG value (12.50 +/- 1.10 mg mL(-1))
      was lower than that of the serum (31.30 +/- 1.20 mg mL(-1)). In pro-estrus, the
      lowest values (S: 27.80 +/- 1.30 mg mL(-1), UF: 9.10 +/- 1.50 mg mL(-1)) were
      obtained. The results showed a lower IgG values in the bovine UF than those of
      the serum in the follicular phase of the cycle, while in di-estrus the UF IgG
      content was the highest, suggesting some IgG production in the uterus at this
      phase. 

PMID- 25568705
TI  - Hydrogen sulfide ameliorates the kidney dysfunction and damage in cisplatin
      induced nephrotoxicity in rat.
AB  - Hydrogen Sulfide (H2S) prevents and treats a variety of disorders via its
      cytoprotective effects. However, the effects of H2S on rats with cisplatin (CP)
      nephrotoxicity are unclear. The aim was to study the effects of H2S on rats with
      CP nephrotoxicity. Thirty male Sprague-Dawley rats were divided into three
      groups: control group, nephrotoxic group received single dose of CP (6 mg kg(-1))
      and nephrotoxic groups that received single dose 100 umol kg(-1) NaHS. On fifth
      day after injection, urine of each rat was collected over a 24-hr period. Animals
      were sacrificed 6 days after CP (or vehicle) treatment, and blood, urine, and
      kidneys were obtained, prepared for light microscopy evaluation, lipid
      peroxidation content and laboratory analysis. The results showed that plasma urea
      (226%), creatinine (271%), renal lipid peroxidation content (151%), Na and K
      fractional excretion, urine protein, volume and kidney weight in CP nephrotoxic
      rats were significantly higher and urine osmolarity and creatinine clearance
      lower than in controls. Increases of the proximal tubular cells apoptosis and
      mesangial matrix in CP nephrotoxicity group rats were observed. Hydrogen sulfide
      reversed the CP-induced changes in the experimental rats H2S prevented the
      progression of CP nephrotoxicity in rats possibly through its cytoprotective
      effects such as antioxidant properties. 

PMID- 25568706
TI  - Detection of Theileria equi and Babesia caballi using microscopic and molecular
      methods in horses in suburb of Urmia, Iran.
AB  - Equine piroplasmosis is a severe disease of horses caused by the intra
      erythrocyte protozoan, Theileria equi and Babesia caballi. The aim of this study
      was to identify equine piroplasmosis based on molecular and morphometrical
      features in horses in suburb of Urmia, West Azerbaijan province, Iran. From April
      to September 2011, a total number of 240 blood samples were collected randomly
      from horses of 25 villages. The specimens were transferred to the laboratory and
      the blood smears stained with Geimsa, and the morphological and biometrical data
      of parasite in any infected erythrocyte were considered. Extracted DNA from each
      blood sample was used in multiplex PCR in order to confirm the presence of B.
      caballi and T. equi. Microscopic observation on 240 blood smears determined that
      15 (6.25%) and 5 (2.80%) samples were infected by T. equi and B. caballi,
      respectively. The mixed infections occurred in 2 (0.83%) samples. The results of
      the PCR assays showed 26 (10.83%), 14 (5.83%) and 4 (1.66%) were distinguished as
      T. equi, B. caballi and mixed infection, respectively. Differences in infection
      rates were statistically nonsignificant between male and female horses and among
      different age groups. Our findings indicated that T. equi and B. caballi were
      prevalent in horse population. 

PMID- 25568708
TI  - Designing and evaluation of Dot-ELISA for diagnosis of Fasciola infection in
      cattle.
AB  - Fasciolosis is a disease caused by liver fluck of the genus of Fasciola.
      Diagnosis of fasciolosis has been challenging for a long period due to low
      sensitivity of the coprological diagnostic method. In this study, an in-house Dot
      ELISA method; using excretion-secretory (ES Ag) and Crude (Cr Ag) antigens of
      Fasciola was described for diagnosis of fasciolosis in cattle. For this purpose,
      the sera specimens of slaughtered cattle were taken and examined for Fasciola
      infection. Sera from two groups of cattle, one infected with Fasciola (n = 60)
      and the other non-infected with Fasciola (n = 60), were used in the Dot- ELISA
      test. All sera were tested and evaluated. Except specificity, other parameters
      such as, sensitivity, accuracy, positive and negative predictive values of Dot-
      ELISA with ES Ag were better than those of Dot- ELISA with Cr Ag. In conclusion,
      excretory-secretory antigen dependent Dot-ELISA can be used as a reliable sero
      diagnostic test for Fasciola infection in cattle. 

PMID- 25568707
TI  - Prevalence of bovine leukemia virus (BLV) infection in the northeast of Iran.
AB  - The purpose of this study was to determine the prevalence of bovine leukemia
      virus (BLV) in Khorasan Razavi and Khorasan Shomali provinces which are the main
      provinces located in the northeast of Iran. Total number of 429 blood samples
      were collected from industrial dairy herds. The samples were categorized based on
      province, age (2-3, 4-6, and 7-10 years old), calving (<= 2, 3-5, and > 5) and
      herd size (<= 100, 101-250, and > 250) and examined by indirect ELISA. The
      results of this study showed that 109 (25.4%) out of 429 serum samples were BLV
      seropositive. The BLV prevalence among cattle of dairy herds of Khorasan Razavi
      and Khorasan Shomali provinces were 29.8% and 1.5%, respectively. The results
      showed that the number of seropositive animals was increased significantly with
      the age (p < 0.05). The infection rate in animals 2-3, 4-6 and 7-10 years old
      were 12.1%, 26.7% and 45.6%, respectively. It was shown that BLV prevalence
      according to calving <= 2, 3-5 and > 5 was 15.5%, 33.0% and 42.9%, respectively,
      with a significant difference between calving <= 2 and > 5 (p < 0.001). The
      prevalence of BLV among herd size of <= 100, 101-250 and > 250 was 19.7%, 14.3%
      and 42.1%, respectively, which was significantly higher in herds with more than
      250 cattle (p < 0.05). This study revealed that BLV infection in dairy herds of
      northeast of Iran was influenced by geographical location (province), age,
      calving and herd size. 

PMID- 25568709
TI  - The response of ducks to V4 Newcastle disease virus and its transmission to
      contact ducks and domestic chickens.
AB  - Experimental infection of Muscovy ducks with V4 strain of Newcastle disease virus
      was undertaken to determine the response of the ducks to the virus and the
      possibility of virus transmission to ducks and chickens in village like
      conditions. Twelve ducks were randomly and equally divided into three groups of
      control, inoculated and in-contact. Additionally, the chickens were placed into
      two groups of four animals each, namely in-contact and control. The inoculated
      and in-contact ducks and in-contact chickens were kept together. The eye drop
      route was used for inoculation and hemagglutination inhibition (HI) antibodies
      were measured for assessment of antibody response and cloacal and pharyngeal
      swabs were used for detection of the virus. The primary antibody response of
      inoculated ducks was very high and rapid (geometric mean titers [Log base 2] of
      up to 5.75 +/- 0.50). The in-contact ducks showed antibody response with the same
      pattern but lower titers than the inoculated ducks (geometric mean titers [Log
      base 2] of up to 3.25 +/- 1.70). The in-contact chickens showed a slight increase
      of HI antibody (geometric mean titers [Log base 2] of up to 2.25 +/- 1.25) while
      the control chickens did not show any increase. The antibody response indicated
      the transmission of the virus to contact ducks and chickens. A single isolation
      of virus confirmed the ability of ducks to excrete the virus. It was concluded
      that the V4 strain of Newcastle disease virus was highly antigenic for ducks, and
      ducks can transmit it to other ducks and also in-contact chickens. 

PMID- 25568710
TI  - Prevalence of immunoglobulin G (IgG) antibody to Neospora caninum in dairy cattle
      of Hamedan province, west of Iran.
AB  - Bovine neosporosis caused by the apicomplexan protozoan parasite N. caninum, was
      initially recognized in 1989 and is now reported as a leading infectious cause of
      reproductive failure in dairy cattle in world wide. The aim of this study was to
      determine the seroprevalence of N. caninum infection in industrial dairy cattle
      of Hamedan province (west of Iran) by ELISA method. Blood samples were collected
      from 492 cattle in 41 farms. Antibodies to N. caninum were found in 63(12.80%)
      sera. A Significant difference was observed between seropositive cattle and dog
      presence in farm, dog contact with herd, abortion history and herd population. No
      significant differences were found between seropositive cattle and age as well as
      breed. This study is the first report of N. caninum infection in dairy cattle
      farms in Hamedan province. As per our knowledge, Neospora is an important factor
      in abortion of cattle in this region. Therefore, comprehensive studies for
      control strategies and improving management of dairy farms is necessary. 

PMID- 25568711
TI  - Congenital peritoneopericardial diaphragmatic hernia in a terrier dog.
AB  - A one-month-old male terrier dog was referred in shock status with a history of
      anorexia, tachypnea, abdominal distention and progressive weight loss.
      Auscultation of right side of the lungs found enhanced respiratory noises. The
      thorough auscultation of the opposite side of the chest revealed the presence of
      typical intestinal sounds. Cardiac auscultation revealed muffled heart sounds and
      a diminished palpable precordial cardiac impulse was evident. The radiograph
      showed the presence of gas within the bowel in abrupt contrast to the adjacent
      structures of soft tissue opacity. Conservative treatment was failed and the
      animal died. At necropsy, cranial displacement of abdominal viscera into the
      pericardial sac was seen. A definitive diagnosis of peritoneopericardial
      diaphragmatic hernia was made. Although congenital pericardial diseases are rare
      in dogs, awareness of the clinical manifestation of these kinds of defects
      combined with early use of available imaging modalities can yield a preoperative
      diagnosis. 

PMID- 25568712
TI  - Hemangiopericytoma in a young dog: Evaluation of histopathological and
      immunohistochemical features.
AB  - In the present study, we describe a subcutaneous mass between the left flank and
      hip in a 2-year-old male Great Dane dog. Histopathologically, cells appeared to
      be spindle shaped around a central capillary together with a fingerprint pattern.
      Immunohistochemical analysis presented that the neoplastic cells expressed
      vimentin, but did not stain for S-100 protein. On the basis of histopathology and
      immunohistochemical findings, the present tumor was diagnosed as canine
      hemangiopericytoma. Hemangiopericytoma could be considered in differential
      diagnosis list of any mass in the skin (even in young dogs) and must be
      identified histopathologically. 

PMID- 25568713
TI  - Clinical, laboratory and pathological findings in sub-acute monensin intoxication
      in goats.
AB  - Toxic effects of monensin, a polyether antibiotic mainly used as a coccidiostat,
      have been described in a wide range of animals. The present study was performed
      to investigate the toxic effects of monensin in goats. Seven adult goats were
      administered sodium monensin, 13.5 mg kg(-1), daily for five consecutive days via
      gastric gavage. Monensin toxicity was evaluated by clinical signs, serum
      biochemistry and pathology. Monensin exposure caused diarrhea, tachycardia and
      reduction in ruminal movements and body temperature. Significant increase of
      creatine kinase, lactate dehydrogenase, aspartate aminotransferase, total
      bilirubin, blood urea nitrogen, creatinine and erythrocyte superoxide dismutase
      were observed in monensin exposed goats. Reduction of erythrocyte glutathione
      peroxidase and elevation of serum malondialdehyde and troponin I were
      inconsistent. In necropsy, there were effusions in body cavities, vacuolar
      degeneration and coagulative necrosis in cardiac and skeletal muscles and renal
      tubular necrosis. These findings suggested that monensin intoxication in goats
      leads to cardiac, skeletal and renal damage and a wide range of biochemical
      abnormalities. Oxidative stress may be involved in the pathogenesis of monensin
      poisoning. 

PMID- 25568714
TI  - Antibacterial activity of Enterococcus faecium derived from Koopeh cheese against
      Listeria monocytogenes in probiotic ultra-filtrated cheese.
AB  - Viability of probiotic bacteria in food during maintenance and time of consuming
      in food has become a challenge in food hygiene and technology and is important
      for representing their beneficial health effects. The aim of this study was to
      determine the survival of probiotic Enterococcus faecium derived from Koopeh
      cheese added to industrial Iranian ultra-filtrated (UF) cheese and screening for
      antimicrobial activity of Enterococcus faecium against Listeria monocytogenes
      during two months of cheese ripening. Physiochemical and standard microbial
      methods were used for isolation of Enterococcus strains in cheese samples. The
      initial number of lactic acid bacteria (LAB) as starter culture was 6 Log g(-1)
      in control samples. The counts started to decrease slightly after day seven (p <
      0.05) and dropped to 5 Log g(-1) at the end of 60 days. The count of LAB in the
      test groups decreased to 11 Log g(-1) on the day 60 of ripening. The number of
      Enterococcus faecium was 6 Log g(-1) on the day 60. The count of Listeria
      monocytogenes after 60 days of ripening in blank sample decreased 1 Log but in
      test samples with protective strain decreased 3 Log in 30 days and reached to
      zero at 45 days. There were not significant (p < 0.05) changes in chemical
      parameters such as fat, protein and total solid of UF cheese treatment groups.
      The results showed that Enterococcus faecium of Koopeh cheese was suitable for
      development of an acceptable probiotic UF cheese and could be adapted to
      industrial production of UF cheese. 

PMID- 25568715
TI  - White side test: A simple and rapid test for evaluation of nonspecific bacterial
      genital infections of repeat breeding cattle.
AB  - The objective of the present study was to determine the grades of nonspecific
      bacterial infection of genitalia of repeat breeding cattle by a simple and rapid
      test under field condition. For this purpose, a total of 100 crossbred Jersey
      cows comprising of 80 repeat breeding animals presented for treatment and 20
      normal cyclic (control group) animals presented for artificial insemination at
      their first service were selected. Estrual cervical mucus from all the animals
      was collected at 8 to 12 hr after the onset of behavioral estrus and subjected to
      white side test (WST) and bacteriological examination. The results of WST showed
      only 15% of control group had infection but the remaining 85% were free of it. In
      contrast, the majority of repeat breeding animals (57/80) showed infection
      (71.25%) and only 28.75% animals were free of infection. In bacterial culture, 60
      (75.00%) from the 80 repeat breeding animals were found positive, and 20 (25.00%)
      were free of bacteria. All the three samples of control group that showed no
      color reaction in WST had also no growth in bacterial culture. The WST results
      showed a positive (p < 0.01) correlation of 0.48 with bacterial culture. It is
      thus concluded that under field condition WST can be used as a prime modality for
      ascertaining nonspecific bacterial infection of repeat breeding cattle before
      subjecting them to any antibiotic therapy thereby reducing the cost of diagnosis
      and treatment. 

PMID- 25568716
TI  - Molecular determination of abundance of infection with Sarcocystis species in
      slaughtered sheep of Urmia, Iran.
AB  - Sarcocystis is one of the most prevalent parasites of domestic ruminants
      worldwide. This study was aimed to determine prevalence of Sarcocystis infection
      and molecular discrimination of Sarcocystis gigantea and Sarcocystis medusiformis
      infecting domestic sheep. Tissue samples from 638 sheep slaughtered at Urmia
      abattoir were randomly collected from February 2011 to January 2012. Genomic DNA
      extraction and polymerase chain reaction (PCR) was performed to amplify a 964 bp
      fragment of nuclear 18S rRNA gene. The PCR products were subjected to digestion
      with endonuclease MboII and/or MvaI for discriminating S. medusiformis and S.
      gigantea. Results indicated that the overall prevalence of Sarcocystis
      unspecified species was 36.83% (235/638) in which male (7.63%, 38/498) and female
      (35.00%, 49/140) sheep over 4 years-old had the highest prevalence. There was no
      significant difference between prevalence of macrosarcocysts and sex. Two
      macrosarcocysts forms were found as fat (27.90%, 178/638) and thin (8.93%,
      57/638) in striated muscles. There was significant difference between frequency
      of macrosarcocysts and body distribution. Mixed infection with both fat and thin
      macrosarcocysts was also found in 11.13% (71/638) of infected sheep. There was no
      significant difference regarding the prevalence of mixed infection in both age
      classes. The PCR-RFLP patterns showed that fat sarcocysts were S. gigantea
      (29.31%, 187/638) and thin sarcocysts were S. medusiformis (7.52%, 48/638). It
      was concluded that ovine Sarcocystis infection was prevalent in Urmia and a
      combination of conventional methods and molecular study for sheep sarcocysts
      could be informative. 

PMID- 25568717
TI  - Phylogenetic characterization of the fusion genes of the Newcastle disease
      viruses isolated in Fars province poultry farms during 2009-2011.
AB  - Despite routine vaccination programs against Newcastle disease (ND), sporadic
      cases have occasionally occurred that remain a constant threat to commercial
      poultry. Ten isolates of Newcastle disease viruses (NDV) from infected broiler
      chicken cases were obtained from various locations in Fars province during 2009
      2011 and genetically analyzed using reverse transcription polymerase chain
      reaction (RT- PCR) with primers specific to the viral fusion (F) protein- gene.
      The viruses were confirmed as NDV by hemagglutination inhibition assay and RT-
      PCR. The isolates based on the sequence and phylogenetic analyses of partial F
      gene were genotypically analyzed by RT PCR. In the present investigation, the
      pathogenicity of NDV strains was determined by internationally recognized test
      mean death time (MDT). Analysis based on F gene showed that characterized
      isolates possess three different types of protease cleavage site motifs and
      appear to show maximum identities with isolates in the region. The subsequent
      phylogenetic analysis was implemented using MEGA and the phylogenetic tree. The
      results of RT-PCR and MDT showed that 10 isolates were positive for NDV, (60%
      velogenic, 30% mesogenic and 10% lentogenic). The results of the phylogenetic
      analysis showed that 10 NDV isolates from Iran belong to the class II, genotype
      III viruses. This information is fundamental to improve the efficacy of
      controlling strategies and vaccine development for NDV. 

PMID- 25568718
TI  - Cardiovascular effects of Adonis aestivalis in anesthetized sheep.
AB  - Adonis aestivalis (summer pheasant-eye) is an annual plant with a crimson flower,
      distributed in southern Europe and Asia. The plant has large buttercup-like
      blossoms and soft, fern-like leaves. It blooms in spring and is often found as a
      weed in cereal fields. Like other Adonis spp., the plant produces cardiac
      glycosides. It is used in remedies for mild weakness of the heart, especially
      when accompanied by nervous complaints. Cardiovascular and toxic effects of a
      hydroalcoholic extract from the aerial parts of A. aestivalis were investigated
      in sheep and mice. Six male sheep were anesthetized with sodium pentobarbital and
      arterial blood pressure was measured with a transducer connected to the left
      femoral artery. Heart rate and electrocardiogram (ECG) were registered from lead
      base-apex ECG derivatives connected to a Powerlab recorder. Three successive
      equal doses (75 mg kg(-1)) of the hydroalcoholic extract of A. aestivalis
      intravenously administered to anesthetized sheep. Adonis aestivalis extract
      induced a significant bradycardia and hypotension in sheep. Various ECG
      abnormalities in sheep included sinus arrhythmia, shortened and depressed S-T
      interval, and absence of P wave and flattened or inverted T wave. In addition,
      ventricular arrhythmias, bradyarrhythmias, atrioventricular block, ventricular
      premature beats, ventricular tachycardia and ventricular fibrillation have also
      been observed. The acute intraperitoneal toxicity (LD50) of the extract in mice
      was 2150 mg kg(-1). In conclusion, bradycardia and ECG alterations induced by the
      extract could explain the justification of traditional use of the of Adonis
      aestivalis in treating cardiovascular insufficiency. 

PMID- 25568719
TI  - Reproductive characteristics and thyroidal function in relation with season in
      Khuzestan buffalo (Bubalus bubalis) bulls.
AB  - High ambient temperature is the major constraint on Buffalo productivity. The aim
      of this study was to evaluate the reproductive performance and thyroid gland
      function in winter and summer seasons in Khuzestan buffalo bulls. Six male
      indigenous buffaloes of Khuzestan with nearly the same age (2-3 years old) and
      weight were used. Semen and blood samples through jugular vein were collected,
      every two weeks throughout the summer and winter seasons. The thyroid hormones
      and thyrotropin stimulating hormone (TSH) concentration in blood serum were
      measured by radioimmunoassay method. Semen quality was determined, using computer
      assisted sperm analyzer (CASA) and routine methods. The concentration of thyroxin
      (T4) was lower in winter than summer (p <= 0.05). The level of T3 uptake was
      higher in cold season than that of in hot season (p <= 0.05). The differences of
      tri-iodotyronine (T3) and TSH concentrations, as well as free thyroxin index were
      not significant between seasons. The semen volume and spermatozoa parameters
      including concentration, progressive motility, linear velocity, mean velocity,
      beat cross frequency, linear coefficient and straightness coefficient were higher
      in winter than summer (p <= 0.05). Semen pH and amplitude of lateral head
      displacement of spermatozoa were higher in summer than winter (p <= 0.05). In
      winter, there was positive correlation between spermatozoa concentration and T3
      value of blood serum (p <= 0.05). There were positive correlations between values
      of semen volume and T4, progressive spermatozoa motility percent and TSH, as well
      as, total motility of spermatozoa and TSH in summer (p <= 0.05). In general,
      thyroid function and semen quality of Khuzestan buffaloes may be affected by
      seasons. 

PMID- 25568720
TI  - Effects of garlic supplementation on energy status of pre-partum Mahabadi goats.
AB  - To evaluate the effects of garlic on some blood metabolites in pre-partum dairy
      goats, the ration was supplemented with raw garlic at the doses of 0, 30, 50 and
      70 g kg(-1) of Dry matter (DM) in eight pregnant Mahabadi breed goats (59 +/- 1
      kg initial live weight) in a replicated Latin square design during the last two
      months of pregnancy. Each experimental period lasted 14 days with the first 12
      days used for diet adaptation and two days of data collection with a 3-days wash
      out period between treatments. The results revealed a beneficial increasing
      effect of garlic (at the level of 70 g kg(-1) of DM) on serum glucose
      concentration (p < 0.05). No effects of garlic supplementation on blood non
      esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), total triglycerides,
      total protein, and albumin concentration were observed, except for serum
      cholesterol concentration, which was reduced (p < 0.05) with 70 g kg(-1) of DM of
      garlic supplementation. Dry matter intake was the same between the different
      treatment groups and throughout the trial period. Concerning the blood indicators
      of negative energy balance, no significant effects were found for NEFA and BHB in
      pre-partum goats however, serum glucose was improved significantly, which showed
      that garlic supplementation may improve the efficiency of feed utilization. In
      conclusion, garlic, as feed additives in ruminant nutrition, holds promise for
      improving feed efficiency and controlling the negative energy balance. 

PMID- 25568721
TI  - Evaluation of antioxidant effects of crocin on sperm quality in cyclophosphamide
      treated adult mice.
AB  - Cyclophosphamide (CP) is one of the anti-neoplastic drugs. Despite its numerous
      clinical applications, it has devastating effects on the testicles and declines
      the sperm quality in treated patients. This study was aimed to investigate the
      protective effect of crocin in improving the toxicity induced by CP in
      reproductive system. In this study, 24 male adult mice (6 to 8 weeks) were
      randomly divided into three groups, control group received normal saline (0.1 mL,
      IP, daily), the CP group received CP (15 mg kg(-1), IP, weekly) and the CP +
      crocin group received CP along with crocin (200 mg kg(-1), IP, daily). After 35
      days of treatment, animals were sacrificed. The samples of epididymis in human
      tubal fluid medium incubated for 30 min in 5% CO2 for flotation of sperm. Sperm
      were obtained from caudal epididymis using dissecting method. Then, the
      parameters of sperm quality including sperm count, motility, viability, DNA
      damage, nuclear maturation, and sperm morphology were evaluated. In CP group, the
      sperm count, motility, viability, nuclear maturation and sperm morphology were
      significantly decreased compared to control group (p < 0.05) and in the CP +
      crocin group all of these parameters significantly increased compared to CP group
      (p < 0.05). The percentage of sperm with DNA damage in the CP group significantly
      increased compared to other groups (p < 0.05). The results of this study
      indicated that the crocin was able to suppress free radicals and enhance the
      quality of sperm in CP treated animals. 

PMID- 25568722
TI  - Comparison between two portal laparoscopy and open surgery for ovariectomy in
      dogs.
AB  - Ovariectomy (OVE) is a routine surgical procedure for neutering in small animal
      practice. Laparoscopy is a new surgical technique which contains advantages such
      as less trauma, smaller incision and excellent visualization than traditional
      open surgery. The present study was conducted to examine the feasibility and
      safety of laparoscopic procedure through two portal comparing with the
      conventional open surgery for OVE in healthy female bitches (n=16). Dogs were
      divided in two equal groups. In laparoscopic group, two 5 and 10 mm portals were
      inserted; First in the umbilicus for introducing the camera and the second,
      caudal to the umbilicus for inserting the forceps. Laparoscopic procedure
      involved grasping and tacking the ovary to the abdominal wall, followed by
      electrocautery, resection and removal of the ovary. In open surgery, routine OVE
      was conducted through an incision from umbilicus to caudal midline. Mean
      operative time, total length of scar, blood loss, clinical and blood parameters
      and all intra and post-operative complications were recorded in both groups. Mean
      operative time, total length of scar, blood loss and post-operative adhesions
      were significantly less in laparoscopic group compared with open surgery. In
      conclusion, laparoscopic OVE is an acceptable procedure due to more advantages in
      comparison with traditional OVE. 

PMID- 25568723
TI  - Effect of water salinity on total protein and electrophoretic pattern of serum
      proteins of grass carp, Ctenopharyngodon idella.
AB  - In this study the effects of water salinity on serum total protein and its
      components in grass carp were investigated. The aim of this study was to
      determine the effect of salinity tolerance of fish on total serum protein level
      and its components as an indicator of liver and kidney activity. One hundred and
      twenty grass carp were divided into four groups, randomly. The first three groups
      were reared in concentration of 4, 8 and 12 g L(-1) of salt solution,
      respectively, and the fourth group was reared in freshwater and served as
      control. After 3 weeks, blood samples were collected and after harvesting the
      blood serum, serum total protein and protein components were measured with Biuret
      and electrophoresis methods, respectively. Results showed that mean value of
      serum total protein in the control and three salinities groups were 2.75, 3.28,
      2.90 and 3.13 g dL(-1), respectively. Five fractions of serum protein were
      electrophoretically observed as: albumin (Alb), alpha-1 globulin (alpha1-glu),
      alpha-2 globulin (alpha2-glu), beta globulin (beta-glu) and gamma globulin (gamma
      glu). There were not any significant differences between the average mean of
      serum total protein of experimental and control groups (p > 0.05). However, Alb,
      alpha1-glu and beta-glu levels in the experimental groups were significantly
      higher than in the control group (p < 0.05). The average of alpha2-glu and gamma
      glu revealed no significant difference between the experimental groups (p >
      0.05). In conclusion, our results showed that increasing water salinity could
      have a significant effect on Alb, alpha1-glu and beta-glu levels but not on total
      serum protein in grass carp. 

PMID- 25568724
TI  - Pathological findings of slaughtered camels' (Camelus dromedaris) kidneys in
      Najaf-Abad, Iran.
AB  - The kidney of camel is known to play a vital role in water conservation through
      the production of highly concentrated urine that may predispose animal to
      varieties of renal dysfunction. In camels renal disorders have received lesser
      attention in comparison with other animals, thus there is shortage of information
      in this area. The present study was conducted on 100 slaughtered camels (Camelus
      dromedaris) (200 kidneys) in Najaf-Abad district (Iran) to evaluate the frequency
      and types of renal disorders. Results demonstrated varieties of gross
      abnormalities in 14.00% of kidneys that out of them, 9.00% were confirmed by
      microscopic examination. Renal capsular pigmentation, medullary hyperemia,
      subcapsular calcification, cortical and medullar discoloration, hemorrhage in
      renal pelvis, nephrolithiasis and hydatidosis were recorded in 3, 6, 5, 6, 3, 2
      and 3 cases, respectively. In addition, capsular melanosis, acute tubular
      necrosis, chronic interstitial nephritis, caseous necrosis, calcification,
      medullary hyperemia, and hydatid cyst were confirmed by histopathological
      examination in 3, 5, 1, 3, 2, 2, and 2 cases, respectively. Our findings indicate
      the presence of many types of renal disorders which may relate to dehydration,
      bacteremia or nephrotoxicosis. In addition capsular melanosis in male camel was
      recorded for the first time and its etiology remains to be addressed. 

PMID- 25568725
TI  - Occurrence of congenital cerebral theileriosis in a newborn twin Holstein calves
      in Iran: Case report.
AB  - An 8-day-old newborn female twin Holstein calves with a history of weakness,
      anorexia, emaciation and convulsion were presented to Tabriz University
      Veterinary Teaching Hospital. On admission, the calves were febrile and
      recumbent. Physical examination revealed many ticks from the external body
      surface of the animals, right and left prescapular lymphadenopathy, severe
      opisthotonos, nystagmus, pedaling, blindness, hyperpnea and hypersthenia. Buccal
      and vaginal mucous were pale and no other physical abnormalities were diagnosed.
      Fecal flotation, complete blood count, bone marrow aspiration, cerebrospinal
      fluid (CSF) analysis, necropsy and histopathological examination were performed.
      Fecal flotation showed no helminth eggs or coccidial oocysts. On blood smears
      obtained from the earlap, >70 percent of erythrocytes were infected with
      piroplasms organisms and schizonts were obvious in smears of lymphocytes lymph
      node. Blood count revealed a lymphopenia, poikilocytosis, anisocytosis and non
      regenerative anemia (packed cell volume; mean, 16%). Histopathological
      examination revealed Arthus reaction through the walls of cerebral blood vessels,
      which resulted in local necrosis of the brain. Analysis of CSF showed no
      abnormality in appearance or biochemical and cell counts. Although the calves
      were treated with a single intramuscular injection of buparvaquone and
      oxytetracycline once daily they did not respond to the treatment and died. In
      conclusion, the present cases showed a rare cerebral form of theileriosis by
      vertical transmission that confirmed by the presence of piroplasms on blood films
      and multinuclear schizonts on lymph node aspiration smears, gross and
      histopathological examinations and unsuccessful treatment in a newborn twin
      Holstein calves. 

PMID- 25568726
TI  - Intravascular hemolysis associated with Candidatus Mycoplasma hematoparvum in a
      non-splenectomized dog in the south region of Iran.
AB  - A 2-year-old male Pekingese dog was referred to Shiraz University's Veterinary
      Teaching Hospital for anorexia and depression. The case had no history of
      surgery. Physical examination revealed no abnormalities except mild depression
      and fever. Small, coccoid, epicellular bacteria were detected on erythrocytes by
      microscopic examination of the Giemsa-stained blood smears. Abnormalities noted
      in the complete blood count included regenerative anemia characterized by a
      marked reticulocytosis. Examination of the plasma showed visual evidence of
      slight intra vascular hemolysis. In addition, Howell-Jolly bodies, nucleated
      RBCs, increased immature neutrophils and thrombocytosis were found in this case.
      The urine was strongly positive for bilirubin, and the urine sediment had
      abundant bilirubin crystals. For polymerase chain reaction (PCR) purpose, total
      DNA was extracted from blood sample collected from dog. PCR was positive and
      phylogenetic analysis of concatenated data showed our isolate clustered within
      Candidatus Mycoplasma hematoparvum group. Treatment was performed by oral
      ciprofloxacin and prednisolone. The clinical signs improved after three days. Two
      month follow-up showed no recurrence. In conclusion, hemoplasmosis should be
      considered as a differential diagnosis in dogs with hemolytic process and
      pyrexia. The PCR evaluation for hemoplasma DNA should be included in the
      investigation of such cases to enable the rapid detection of this infection,
      which may be more common than previously estimated. Besides, ciprofloxacin might
      have an effect on treatment of hemoplasma in dogs, however, conducting further
      case studies are necessary to recommend successful treatment. 

PMID- 25568727
TI  - Long term results in refractory tennis elbow using autologous blood.
AB  - Tennis elbow (TE) is one of the commonest myotendinosis. Different treatment
      options are available and autologous blood injection has emerged as the one of
      the acceptable modalities of treatment. Long term studies over a larger group of
      patients are however lacking. The purpose of this study was to evaluate these
      patients on longer durations. One-hundred and twenty patients of TE, who failed
      to respond to conventional treatment including local steroid injections were
      taken up for this prospective study over the period from year 2005 to 2011 and
      were followed up for the minimum of 3 years (range 3-9 years). Two mL of
      autologous blood was taken from the ipsilateral limb and injected into the
      lateral epicondyle. The effectiveness of the procedure was assessed by Pain
      Rating Sscale and Nirschl Staging, which was monitored before the procedure, at
      first week, monthly for first three months, at 6 months and then 3 monthly for
      first year, six monthly for next 2 years and then yearly. Statistical analysis
      was done and a P value of <0.05 was taken as significant. The patients (76
      females and 44 males) were evaluated after procedure. The mean age group was
      40.67+/-8.21. The mean follow up was 5.7+/-1.72 (range 3 to 9 years). The mean
      pain score and Nirschl stage before the procedure was 3.3+/-0.9 and 6.2+/-0.82
      respectively. At final follow up the pain score and Nirschl were 1.1+/-0.9 and
      1.5+/-0.91 respectively. Autologous blood injection was found to be one of the
      modalities for treatment of TE. Being cheap, available and easy method of
      treatment, it should be considered as a treatment modality before opting for the
      surgery. Universal guidelines for the management of tennis elbow should be made
      as there is lot of controversy regarding the treatment. 

PMID- 25568729
TI  - Post-operative quality of life in children with severe perthes disease:
      differences to matched controls and correlation with clinical function.
AB  - The diagnosis of Legg-Calve-Perthes disease (LCPD) has a considerable influence
      on the daily life of the patients with restrictions in their leisure time
      activities. This might influence their mood. Until now this aspect of the disease
      has been neglected. Therefore the objective of the study was to evaluate the
      health related quality of life (HRQoL) of children with severe LCPD who had an
      extensive surgery with pelvic/femoral osteotomy. The KIDSCREEN-10 and the
      modified Modified Harris Hip Score (mHHS) -questionnaire were administered to 17
      children (16 boys and 1 girl) aged 5 to 11 years at the time of surgery. Analyses
      of mHHS were made preoperatively and at the time of the follow-up examination at
      least 2 years postoperatively. KIDSCREEN-analyses were made postoperatively. The
      follow-up results were compared to an age-matched normal control group.
      Correlations were computed between KIDSCREEN-10 and mHHS pre- and post
      operatively. The postoperative calculated KIDSCREEN-10-T-value [70.2 (SD 12.7)]
      was higher than the mean T-value of the control-group [56.6 (SD 10.4)]. The mHHS
      improved from 54.4 (SD 19.9) to a score of 99.5 (SD 1.5) postoperatively. A
      strong correlation was found between the preoperative mHHS and the postoperative
      KIDSCREEN-10-T-value (Spearman's-rho 0.67, P=0.003). After containment improving
      surgery and a mean follow-up period of 4.2 years the HRQoL-status is even better
      compared with a healthy age-matched control group. As well an excellent clinical
      function could be achieved. 

PMID- 25568728
TI  - Bilateral simultaneous anterior cruciate ligament injury: a case report and
      national survey of orthopedic surgeon management preference.
AB  - Unilateral anterior cruciate ligament (ACL) tear is a common injury seen by
      sports medicine orthopedic surgeons. However, a bilateral simultaneous ACL injury
      is extremely rare and has been reported only three times in the literature. We
      present a young female skier with simultaneous bilateral ACL tears that were
      managed with staged ACL reconstruction. We then conducted a nationwide survey
      (United States) to determine the prevalence of simultaneous bilateral ACL tear
      and preferred management strategies by sports medicine orthopedic surgeons.
      Sports medicine fellowship directors were contacted and asked to send an 8-item
      survey to colleagues (sports medicine fellowship trained surgeons) asking about
      overall number of ACL reconstructions performed, number of bilateral simultaneous
      ACL injuries seen and optimal management strategies of such an injury. Out of 43
      responses, only 22 (51.2%) surgeons had seen a bilateral simultaneous ACL injury.
      Of these, 16 (76.2%) preferred staged reconstruction. Graft choice was mixed
      between autograft and allograft, but a large majority preferred either patellar
      tendon autograft (58%) or hamstring autograft (41%) were the most common choice.
      Staged reconstruction is the treatment of choice by surgeons surveyed in our
      study. 

PMID- 25568730
TI  - Non-osteotomy and osteotomy large animal fracture models in orthopedic trauma
      research.
AB  - Large animal fracture models are important in the field of orthopedic trauma
      research. New implants are tested in animals before being implanted into humans.
      Large animals like sheep or swine often are more properly to simulate conditions
      in humans, e.g. biomechanical demands, compared to rodents. Cited articles mainly
      analyze shock or fracture healing. Both osteotomy and non-osteotomy fracture
      models have been used in the past. However, comparative studies are rare and
      clear recommendation when to use which model are missing. This review will
      summarize large animal fracture models putting special emphasis on non-osteotomy
      fracture models. 

PMID- 25568732
TI  - Differences in injury pattern and prevalence of cartilage lesions in knee and
      ankle joints: a retrospective cohort study.
AB  - Osteoarthritis (OA) is more common in the knee compared to the ankle joint. This
      can not be explained exclusively by anatomical and biomechanical differences. The
      aim of this study is to analyze and compare the injury pattern (clinically) and
      the cartilage lesions (arthroscopically) of knee and ankle joints in a cohort of
      patients from the same catchment area. A retrospective study of the clinical data
      of 3122 patients (2139 outpatients and 983 inpatients) was performed, who were
      treated due to an injury of the knee and ankle joint. Statistical analysis was
      performed using SigmaStat 3.0 (SPSS Inc, Chicago, USA). There is a higher
      prevalence of injuries in the ankle as compared to the knee joint in this
      population from the same catchment area. In contrast, high-grade cartilage
      lesions are more prevalent in the knee, whereas low grade cartilage lesions are
      equally distributed between knee and ankle. From this data it can be concluded
      that the frequency of injuries and the injury pattern of knee versus ankle joints
      do not correlate with the severity of cartilage lesions and may therefore have no
      direct influence on the differential incidence of OA in those two joints. 

PMID- 25568731
TI  - The 100 most cited papers in spinal deformity surgery: a bibliometric analysis.
AB  - Spinal deformity is a condition that has been recognized for many millennia.
      There have been major advances in the treatment of spinal deformity in recent
      years and studies outlining new ideas can inspire others to further advance the
      speciality. The number of citations a paper receives may indicate the influence
      of that paper. It is therefore important that we evaluate and analyze the most
      cited works in our field. The aim of this study is to identify the 100 most cited
      papers relevant to spinal deformity surgery in the literature. A search through
      the Thomson Reuters Web of ScienceTM for citations related to spinal deformity
      surgery was performed. The number of citations, mean citation number (total
      number citations/years since publication), journal, authors, year of publication
      and country of origin of the top 100 papers was recorded. The top 100 papers were
      cited a combined 17,646 times, ranging from 453 to 112. The majority of papers
      originated from the United States (71) and were published in 20 different
      journals. The decade 1990-1999 was the most prolific, with 36 of the 100 papers
      published during this time. Papers pertaining to the management of scoliosis (49)
      were the most common. This study identifies the top 100 most cited papers in the
      field of spinal deformity surgery. While citation is not a specific marker of the
      scientific quality of a paper, it is a surrogate for the influence a paper has
      had on the orthopedic community. This list of papers provides an invaluable
      resource for both those in training and those actively practicing and involved in
      the further development of spinal deformity surgery. 

PMID- 25568733
TI  - Intramuscular lipoma: a review of the literature.
AB  - Lipomas are the most common type of soft tissue mesenchymal tumors. They are
      typically located subcutaneously and consist of mature fatty tissue. When they
      occur under the enclosing fascia, they are called deep-seated lipomas.
      Infrequently, lipomas can arise inside the muscle and are called intramuscular
      lipomas. Intramuscular lipomas have been commonly investigated and categorized in
      the same group as other deep-seated and superficial lipomatous lesions. Their
      clinical, histological and imaging characteristics may resemble well
      differentiated liposarcomas, further adding to the difficulties in the
      differential diagnosis. This article summarizes the available literature and
      describes the typical epidemiological, pathological and clinical features of
      intramuscular lipomas, as well as delineating their treatment and prognosis. 

PMID- 25568735
TI  - Botulinum toxin type a for cephalic cutaneous allodynia in chronic migraine: a
      randomized, double-blinded, placebo-controlled trial.
AB  - Cephalic allodynia (CA) can be observed in 50-70% of patients with chronic
      migraine (CM). The aim of this trial was to assess the efficacy of botulinum
      toxin type A (Botx-A) in the treatment of CA associated with CM. In this placebo
      controlled trial, patients were randomized either into Botx-A or 0.9% saline
      injections and efficacy measures were assessed every 4 weeks for 3 months.
      Efficacy endpoints were number of migraine episodes associated with CA, changes
      from baseline in visual analogical scale scores for pain (VAS) and frequency of
      common analgesics use for migraine. A total of 38 subjects were randomized to
      saline (n=18) or Botx-A (n=20). There were no significant differences in baseline
      between active intervention or placebo groups regarding mean age, number of
      headache episodes [mean 12.1 (9.22) and 17.00 (9.69) respectively; P=0.12], pain
      severity as measured by the VAS or frequency of analgesic use for headache
      episodes. Efficacy analysis showed that Botx-A injections led to an important
      decrease from baseline in the mean migraine episodes associated with CA after 12
      weeks (5.20 versus 11.17; P=0.01). Also, VAS scores and frequency of analgesics
      use for headache were significantly reduced in the Botx-A group. This study
      suggests that Botx-A injections are superior to saline in the treatment of CA
      associated with CM, with mild self limited side effects. 

PMID- 25568734
TI  - Adolescent differences in knee stability following computer-assisted anterior
      cruciate ligament reconstruction.
AB  - Anterior cruciate ligament (ACL) surgery is being increasingly performed in the
      adolescent population. Computer navigation offers a reliable way to
      quantitatively measure knee stability during ACL reconstruction. A retrospective
      review of all adolescent patients (<18 years old) who underwent computer-assisted
      primary single bundle ACL reconstruction by a single surgeon from 2007 to 2012
      was performed. The average age was 15.8 years (SD 3.3). Female adolescents were
      found to have higher internal rotation than male adolescents both pre- (25.6
      degrees  vs 21.7 degrees , P=0.026) and post-reconstruction (20.1 degrees  vs
      15.1 degrees , P=0.005). Compared to adults, adolescents demonstrated
      significantly higher internal rotation both pre- (23.3 degrees  vs 21.5 degrees ,
      P=0.047) and post-reconstruction (17.1 degrees  vs 14.4 degrees , P=0.003). They
      also had higher total rotation both pre- (40.9 degrees  vs 38.4 degrees , P=0.02)
      and post-reconstruction when compared to adults (31.56 degrees  vs 28.67 degrees
      , P=0.005). In adolescent patients, anterior translation was corrected more than
      rotation. Females had higher pre- and residual post-reconstruction internal
      rotation compared to males. When compared to adults, adolescents had increased
      internal rotation and total rotation both pre-and post-reconstruction. 

PMID- 25568737
TI  - Sensitivity of 3D Gradient Recalled Echo Susceptibility-Weighted Imaging
      Technique Compared to Computed Tomography Angiography for Detection of Middle
      Cerebral Artery Thrombus in Acute Stroke.
AB  - We aimed at comparing the sensitivity of magnetic resonance (MR) susceptibility
      weighted imaging (SWI) with computed tomography angiography (CTA) in the
      detection of middle cerebral artery (MCA) thrombus in acute stroke. Seventy-nine
      patients with acute MCA stroke was selected using our search engine software;
      only the ones showing restricted diffusion in the MCA territory on diffusion
      weighted images were included. We finally selected 35 patients who had done both
      MRI (including SWI) and CTA. Twenty random subjects with completely normal MRI
      (including SWI) exam were selected as control. Two neuroradiologists (blinded to
      the presence or absence of stroke) reviewed the SW images and then compared the
      findings with CT angiogram (in patients with stroke). The number of MCA segments
      showing thrombus in each patient was tabulated to estimate the thrombus burden.
      Thrombus was detected on SWI in one or more MCA segments in 30 out of 35
      patients, on the first review. Of the 30, SWI showed thrombus in more than one
      MCA segments in 7 patients. CTA depicted branch occlusion in 31 cases. Thrombus
      was seen on both SWI and CTA in 28 patients. Thrombus was noted in two patients
      on SWI only, with no corresponding abnormality seen on CTA. Two patients with
      acute MCA showed no vascular occlusion or thrombus on either CTA or SWI. Only two
      case of false-positive thrombus was reported in normal control subjects.
      Susceptibility-weighted images had sensitivity and specificity of 86% and 90%
      respectively, with positive predictive value 94%. Sensitivity was 86% for SWI,
      compared with 89% for CTA, and this difference was statistically insignificant
      (P>0.05). Of all the positive cases on CTA (31) corresponding thrombus was seen
      on SWI in 90% of subjects (28 of 31). Susceptibility-weighted imaging has high
      sensitivity for detection of thrombus in acute MCA stroke. Moreover, SWI is a
      powerful technique for estimation of thrombus burden, which can be challenging on
      CTA. 

PMID- 25568736
TI  - Resting metabolic rate analysis in chronic hemiparesis patients.
AB  - The objective of the present study was to compare resting metabolic rate (RMR) of
      chronic hemiparetic patients to sedentary health individuals. The sample was
      composed of 16 individuals, that were divided into two groups. The first group
      had eight hemiparetic patients and the second group was formed by eight sedentary
      individuals. To access and analyze the gases information a VO2000 analyzer was
      used. The following variables were measured: VO2, VCO2, VE, QR, grams of fat
      (GrFAT), grams of carbohydrate. RMR was calculated based on Weir's equation.
      There was a significant shift on ventilation variables: VE (P<0.0003), VO2
      (P<0.0004) and VCO2 (P<0.0001) on hemiparetic individuals group when compared to
      control group. When the energetic substrate used behavior is observed, it shows
      that fat consumption (represented by GrFAT) is higher on the hemiparetic group
      when compared to controls (P<0.0001) significant differences were observed for
      RMR between groups (P<0.0001). RMR showed a correlation to VO2 on the hemiparetic
      group (r=0.9277, P=0.0022). To sum up, it was observed through the results that
      individuals with hemiparesis as a sequel of stroke showed a RMR larger than
      normal individuals. 

PMID- 25568738
TI  - Neuroimaging abnormalities and seizure recurrence in a prospective cohort study
      of zambians with human immunodeficiency virus and first seizure.
AB  - In HIV-positive individuals with first seizure, we describe neuroimaging
      findings, detail clinical and demographic risk factors for imaging abnormalities,
      and evaluate the relationship between imaging abnormalities and seizure
      recurrence to determine if imaging abnormalities predict recurrent seizures.
      Among 43 participants (mean 37.4 years, 56% were male), 16 (37%) were on
      antiretroviral drugs, 32 (79%) had advanced HIV disease, and (28) 66% had
      multiple seizures and/or status epilepticus at enrollment. Among those with
      cerebrospinal fluid studies, 14/31 (44%) had opportunistic infections (OIs).
      During follow-up, 9 (21%) died and 15 (35%) experienced recurrent seizures. Edema
      was associated with OIs (odds ratio: 8.79; confidence interval: 1.03-236) and
      subcortical atrophy with poorer scores on the International HIV Dementia Scale)
      (5.2 vs. 9.3; P=0.002). Imaging abnormalities were not associated with seizure
      recurrence or death (P>0.05). Seizure recurrence occurred in at least a third and
      over 20% died during follow-up. Imaging was not predictive of recurrent seizure
      or death, but imaging abnormalities may offer additional diagnostic insights in
      terms of OI risk and cognitive impairment. 

PMID- 25568739
TI  - Radiation-induced spinal cord hemorrhage (hematomyelia).
AB  - Intraspinal hemorrhage is very rare and intramedullary hemorrhage, also called
      hematomyelia, is the rarest form of intraspinal hemorrhage, usually related to
      trauma. Spinal vascular malformations such intradural arteriovenous malformations
      are the most common cause of atraumatic hematomyelia. Other considerations
      include warfarin or heparin anticoagulation, bleeding disorders, spinal cord
      tumors. Radiation-induced hematomyelia of the cord is exceedingly rare with only
      one case in literature to date. We report the case of an 8 year old girl with
      Ewing's sarcoma of the thoracic vertebra, under radiation therapy, presenting
      with hematomyelia. We describe the clinical course, the findings on imaging
      studies and the available information in the literature. Recognition of the
      clinical pattern of spinal cord injury should lead clinicians to perform imaging
      studies to evaluate for compressive etiologies. 

PMID- 25568740
TI  - Therapeutic drug monitoring in epilepsy clinic: a multi-disciplinary approach.
AB  - Epilepsy is a common public health problem and needs multi-disciplinary
      treatment. Therapeutic drug monitoring (TDM) is one of step of the multi
      disciplinary treatment in epilepsy at Epilepsy clinic, Khon Kaen University
      (Thailand). The TDM service has been established since 2008. Here, we aimed to
      study the roles of TDM order and epilepsy control. This is a prospective
      descriptive study in which data collection was done from January 1 to December
      31, 2010, the period when pharmacists took part in assessing the appropriateness
      in measurement and interpretation of TDM in order to provide suggestions for
      physicians. The 112 patients under study had an average age of 38.21+/-15.36
      years; 254 samples were collected for therapeutic drug monitoring; phenytoin was
      submitted mostly for drug monitoring at 46.46%; 44.49% of submissions for drug
      level monitoring were made owing to a suspected sub-therapeutic level.
      Associations were found between reasons of sending samples for drug level
      monitoring and the measured drug levels, i.e., 66.67% of drug levels found was so
      low that they were undetectable in sample for patients' compliance investigation
      and 38.94% of the drug levels were found to be sub-therapeutic as for the case
      where submission of samples was done because of suspected sub-therapeutic level,
      40% of the cases were found to be in toxicity range in the cases with suspected
      over-therapeutic levels and monitoring levels, 58.25% were found to be within the
      therapeutic range. Pharmacists used the interpreted results in patients' care by
      recommending physicians to monitor therapeutic drug closely, to adjust the dosage
      of drugs, and to recommend checking patients' compliance in their use of drugs at
      56.5, 38.9, and 4.3%, respectively. Physicians' responses were found to be
      absolute follow, partial follow and not follow at 77.95, 11.03, and 7.48%,
      respectively. In conclusion, associations were found between reasons of TDM order
      and measured drug level. Therapeutic drug monitoring services at the Epilepsy
      Clinic was useful in supporting clinical information queries. Pharmacists could
      make use of interpreted drug level information by recommending physicians to
      monitor drug levels and adjust individual dosage regimen accordingly. It should
      be noted that physicians accepted pharmacists' recommendation, denoting multi
      disciplinary care team that would lead to greater efficiency. 

PMID- 25568741
TI  - A late-onset seizure in a child due to intracranial needle.
AB  - Placing of sewing needles in the brain through the anterior fontanel is a rare
      entity. There are very few cases reported in literature. Most of them were
      asymptomatic, but some of them presented with seizure. We report here a 14-year
      old boy, who was admitted to the Pediatric Neurology Department with a history of
      generalized tonic-clonic seizures due to sewing needle located in the frontal
      lobe. 

PMID- 25568742
TI  - Pincer nail deformity in a patient with amyotrophic lateral sclerosis.
AB  - Although several manifestations of skin involvement in cases of amyotrophic
      lateral sclerosis (ALS) have been reported, the pincer nail deformity has not
      been previously reported in a patient with ALS. The pincer nail deformity is
      characterized by distortion of the shape of the nail with transverse over
      curvature and may be associated with systemic diseases and certain medications.
      We herein describe the case of a patient presenting with a pincer nail deformity
      associated with rapidly advancing ALS. This case suggests a potential link
      between quickly advancing disease and the pincer nail deformity. 

PMID- 25568744
TI  - Blastic plasmacytoid dendritic cell neoplasm with extensive cutaneous and central
      nervous system involvement.
AB  - Blastic plasmacytoid dendritic neoplasm is an exceedingly rare tumor that has
      undergone several changes in nomenclature over the last two decades, largely
      because of confusion regarding its cell of origin. It does, however, have
      distinctive clinical features with a particularly aggressive clinical course and
      no standard treatment. Overall, prognosis is poor and relapse is routine after
      initial response to chemotherapy. In this report, we describe a typical patient
      with this disease and reconcile the available literature and its evolution. We
      emphasize the leukemic nature of this tumor's behavior, with extensive central
      nervous system and skin involvement, and describe for the first time a potential
      role for maintenance chemotherapy in its treatment. 

PMID- 25568743
TI  - Primary Gastric Burkitt's Lymphoma.
AB  - The primary gastrointestinal non-Hodgkin's lymphoma, although rare, is among the
      most common extra-nodal lymphomas, considering that gastric lymphomas are more
      common than intestinal lymphomas. Burkitt's lymphoma (BL) is an aggressive form
      of B-cell lymphoma that is typically endemic in Africa, while non-endemic cases
      are found in the rest of the world. Primary gastric BL is extremely rare and only
      around 50 cases have been reported worldwide. Here we present the case of a young
      HIV-negative male, who was referred to our department with a stage IV gastric BL.
      He was planned for palliative chemotherapy, but after the first cycle of
      chemotherapy he succumbed to the progression of the disease. 

PMID- 25568745
TI  - Mucinous urothelial carcinoma of the renal pelvis.
AB  - Urothelial carcinoma with abundant myxoid stroma is a newly-described and
      extremely rare entity. Since only very few cases have been reported, there is no
      consensus on its nomenclature. Microscopic examination revealed invasive
      urothelial carcinoma with widespread low-grade noninvasive areas. There were
      focal invasive areas in the neighborhood of the renal parenchyma. Malignant
      urothelial tumor/cell groups localized in the stroma had abundant myxoid/mucinous
      background in the invasive areas. The cytoplasm of the tumoral cells was more
      eosinophilic in these areas and the cells formed small groups and cords.
      Histochemically, PAS and Alcian Blue were positive in the cytoplasm of the
      tumoral cells and in the stroma while negative in the non-mucinous areas.
      Immunohistochemically, the tumoral cells of the mucinous invasive areas diffusely
      expressed MUC1 and MUC2. We discuss the origin of the mucinous/myxoid stroma, the
      tumor's nature and its nomenclature with histochemical and immunohistochemical
      features. 

PMID- 25568746
TI  - Malignant peripheral nerve sheath tumor of the anterior mediastinum: a rare
      presentation.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is a rare tumor that accounts for
      5% of all thoracic neoplasm usually located in the posterior mediastinum and is
      generally associated with a poor outcome. We present a case of MPNST of the
      anterior mediastinum presenting in a rare location leading to diagnostic dilemmas
      and treated primarily by surgical resection. 

PMID- 25568747
TI  - Response to targeted therapy in urachal adenocarcinoma.
AB  - We report the case of a young woman diagnosed with metastatic urachal carcinoma.
      A multimodal approach was used for the management of this patient. Due to disease
      progression despite surgery and two different chemotherapy regimens (neoadjuvant
      capecitabine + irinotecan + oxaliplatin and docetaxel + cisplatin after surgery),
      treatment with sunitinib was eventually started. Treatment with sunitinib
      resulted in stable disease and improvement of symptoms. Sunitinib was
      discontinued due to the occurrence of metrorrhagia, and restarted one week later.
      Disease eventually progressed and the patient died 18 months after the onset of
      symptoms. This is the first report on the use of sunitinib for the management of
      urachal carcinoma and provides initial evidence supporting the use of targeted
      therapy in this setting. 

PMID- 25568748
TI  - Extranodal rosai-dorfman disease of the bone treated with surgery and
      radiotherapy.
AB  - Rosai-Dorfman disease (RDD) is a rare, benign histiocyte disorder originally
      described by Rosai and Dorfman in 1969 as sinus histiocytosis with massive
      lymphadenopathy. It most typically presents as massive, painless cervical
      lymphadenopathy, and it is most often found in adolescents and young adults.
      Extranodal involvement is a common feature of RDD and may occur in more than 40%
      of patients. Less commonly, the disease can be seen in the bone. There are
      scattered case reports discussing the use of radiotherapy in the treatment of
      RDD. Here, we present a case of extranodal RDD of the femur in a 49-year-old
      African American female. The patient underwent three surgical procedures prior to
      undergoing radiotherapy. Pathology was consistent with extranodal RDD. The cells
      stained positive for CD68 and S-100. Pathognomonic features such as emperipolesis
      and replacement of the bone marrow by diffuse infiltrating of histiocytes and
      intervening bands of plasma cells proliferation were noted. Prior to
      radiotherapy, the patient required a walker to assist with ambulation and was
      utilizing a wheelchair while in the clinic. The decision was made to proceed with
      30 Gy of external beam radiotherapy in 15 fractions. After five fractions, the
      patient's pain resolved entirely. She no longer required pain medication and was
      ambulating without assistance. She experienced no adverse events from the
      radiation. Extranodal RDD is a rare disorder, and evidence for treatment is
      derived from scattered case reports. Previous reports have indicated a dose
      response to radiotherapy in the 20-30 Gy range for RDD; however, our patient
      developed complete resolution of her symptoms after 10 Gy. While the optimal dose
      regimen has not yet been established, symptomatic patients appear to benefit from
      external beam radiotherapy for extranodal RDD. 

PMID- 25568749
TI  - Spontaneous rupture of the kidney affected by multifocal papillary renal cell
      carcinoma.
AB  - Papillary renal cell carcinoma (pRCC) represents the second most common type of
      malignant renal epithelial tumor (represents the 10% of the kidney's carcinoma)
      and can be subclassified in the basophile type I and eosinophile type II. We
      report a clinical case of spontaneous rupture of the kidney affected by
      multifocal (42 tumors foci) pRCC in a young man 53 years old, without showing
      earlier specific cancer signs and symptoms. Prognosis for type I pRCC is better
      than type II pRCC, but it is anyway related to the tumoral grade, to the tumoral
      stage and to the diagnostic precocity. Signs and symptoms are very similar to
      those characterizing the more frequent clear cell carcinoma. Nevertheless in the
      40% of the cases the lesion is asymptomatic. To our knowledge, this is the first
      case of spontaneous rupture of the kidney affected by multifocal pRCC in
      literature without showing earlier specific cancer signs and symptoms. 

PMID- 25568750
TI  - Interdigitating dendritic cell sarcoma presenting in the skin: diagnosis and the
      role of surgical resection, chemotherapy and radiotherapy in management.
AB  - We report the case of an interdigitating dendritic cell sarcoma (IDCS) presenting
      in the skin. A 41-year old woman had a slowly enlarging mass on her right scapula
      that was excised multiple times under a presumptive diagnosis of a recurrent
      sebaceous cyst. However, the lesion was refractory to standard therapies. History
      and physical exam was unrevealing for any systemic signs or symptoms of disease.
      The patient's metastatic work-up was negative. The lesion was resected with wide
      margins and was found to be consistent with IDCS. Patients that present with IDCS
      on the skin may present concurrently with metastatic disease and may have
      increased risk of secondary malignancies. The use of adjuvant chemoradiation
      after primary resection is controversial. However, the use of chemoradiation
      likely has benefit for local regional control for primary tumors that are
      unamendable to complete primary resection. 

PMID- 25568751
TI  - Extraskeletal myxoid chondrosarcoma presenting as an intradural spinal mass:
      report of a rare clinical presentation with an emphasis on differential
      diagnostic considerations.
AB  - Extraskeletal myxoid chondrosarcoma is a rare soft tissue neoplasm that occurs
      predominantly in the soft tissues of the lower extremities. Herein we present a
      case of a 29 year old male who presented with bilateral femoral numbness believed
      to be the result of prior injury to his back. A magnetic resonance imaging
      revealed a mass in the T4-T5 epidural space compressing the spinal cord.
      Laminectomy was performed and the lesion removed piecemeal. The pathology
      specimen consisted of multiple fragments of dura involved by a myxoid neoplasm
      with a nodular growth pattern. The tumor cells were arranged in anastomosing
      cords and strands. Individual tumor cells were small, of uniform size and shape,
      with small hyperchromatic nuclei and scant eosinophilic cytoplasm.
      Immunohistochemical stains were performed which showed the tumor cells were
      diffusely positive for vimentin and focally positive for EMA, S-100 protein and
      cytokeratin, whereas they were negative for CD34 and CD99. Fluorescence in situ
      hybridization (FISH) studies showed a clonal population of cells with re
      arrangement of the EWSR1 locus, confirming the histologic impression of
      extraskeletal myxoid chondrosarcoma. This is the first report of a case of an
      extraskeletal myxoid chondrosarcoma arising from the dura, confirmed to have
      rearrangement of the EWSR1 gene by FISH. There have only been two other cases of
      dural based extraskeletal myxoid chondrosarcoma reported prior to our case. We
      also briefly review the published literature and discuss differential diagnostic
      considerations for this rare tumor. 

PMID- 25568752
TI  - Knee glomangioma: a rare location for a glomus tumor.
AB  - Glomus tumor is a rare, benign neoplasm rising from the glomus apparatus of the
      skin. It occurs most frequently on fingers and toes and accounts for 1.6% of all
      soft tissue tumors. Clinical diagnosis may prove difficult if the tumor occurs on
      an extra digital location. We report a case of a vascular-type glomus tumor
      (glomangioma) found in an atypical location, namely the lateral aspect of the
      knee joint. 

PMID- 25568753
TI  - Prostatic stromal sarcoma in an adolescent: the role of chemotherapy.
AB  - Prostatic stromal sarcoma (PSS) is a rare tumor that normally occurs in adult
      age. Its management relies mainly on surgery. We report the first case of PSS
      occurring in an adolescent. There was evidence of a good response to chemotherapy
      including ifosfamide, doxorubicin, vincristine and actinomycin-D, although the
      final outcome was dismal. A review of the English literature revealed 14
      additional patients with PSS treated with chemotherapy: tumor shrinkage was
      reported in 4 of the 6 evaluable patients. Patients with PSS may benefit from the
      use of chemotherapy in combination with early aggressive local treatment. 

PMID- 25568754
TI  - Brucellosis associated with deep vein thrombosis.
AB  - Over the past 10 years more than 700 cases of brucellosis have been reported in
      Kosovo, which is heavily oriented towards agriculture and animal husbandry. Here,
      brucellosis is still endemic and represents an uncontrolled public health
      problem. Human brucellosis may present with a broad spectrum of clinical
      manifestations; among them, vascular complications are uncommon. Hereby we
      describe the case of a 37-year-old male patient with brucellosis complicated by
      deep vein thrombosis on his left leg. 

PMID- 25568755
TI  - A case of chronic progressive lyme encephalitis as a manifestation of late lyme
      neuroborreliosis.
AB  - A 54-year-old female living in Europe presented with gait ataxia, dizziness, and
      bilateral hearing loss. Magnetic resonance imaging (MRI) revealed non-specific
      white matter changes. The patient's condition gradually deteriorated over two
      years without diagnosis. The patient continued to decline cognitively and
      neurologically with worsening ataxia and upper motor neuron signs. Repeat MRI
      showed worsening white matter changes. Lumbar puncture, not previously done,
      showed positive Lyme testing. Treatment with intravenous ceftriaxone resulted in
      marked neurological improvement. Four years after symptom, the patient has short
      term memory deficits and chronic fatigue, but is otherwise neurologically,
      cognitively, and functionally intact. Follow up MRI findings remain largely
      unchanged. Because cases of intraparenchymal or encephalopathic neuroborreliosis
      in America are lacking, so are treatment options. We present a rare case and
      discuss our experience with antibiotic treatment. This case lends evidence to
      define optimal treatment of this disease, imperative for hastening neurological
      recovery. 

PMID- 25568757
TI  - Detection of hand, foot and mouth disease in the yucatan peninsula of Mexico.
AB  - We report a case of hand, foot and mouth disease (HFMD) in a 5-year-old male from
      Merida City in the Yucatan Peninsula of Mexico. A clinical and physical
      examination revealed that the patient had symptoms typical of HFMD, including
      fever, fatigue, odynophagia, throat edema, hyperemia, lesions on the hands and
      feet, and blisters in the oral cavity. The patient fully recovered after a
      convalescence period of almost three weeks. Reverse transcription-polymerase
      chain reaction and nucleotide sequencing revealed that the etiological agent was
      enterovirus 71 (EV71). The sequence has greatest (90.4%) nucleotide identity to
      the corresponding regions of EV71 isolates from the Netherlands and Singapore.
      Although HFMD is presumably common in Mexico, surprisingly there are no data in
      the PubMed database to support this. This case report provides the first peer
      reviewed evidence of HFMD in Mexico. 

PMID- 25568756
TI  - Extensive Central Nervous System Cryptococcal Disease Presenting as Immune
      Reconstitution Syndrome in a Patient with Advanced HIV: Report of a Case and
      Review of Management Dilemmas and Strategies.
AB  - One of the complications of the use of antiretroviral therapy (ART), immune
      reconstitution inflammatory syndrome (IRIS), is particularly problematic in the
      management of cryptococcal meningitis. We present the case of a 35-year-old male
      with acquired immune deficiency syndrome diagnosed with extensive central nervous
      system (CNS) cryptococcal disease, including meningitis and multiple intracranial
      cysts, diagnosed eight weeks after the initiation of ART. The patient experienced
      a relapsing and remitting clinical course despite repeated courses of potent
      antifungal therapy and aggressive management of raised intracranial pressure.
      This review highlights therapeutic dilemmas and strategies in the management of
      CNS cryptococcosis complicated with IRIS and highlights gaps in available
      treatment guidelines. 

PMID- 25568758
TI  - High prevalence of clustered tuberculosis cases in peruvian migrants in florence,
      Italy.
AB  - Tuberculosis is a leading cause of morbidity for Peruvian migrants in Florence,
      Italy, where they account for about 20% of yearly diagnosed cases. A
      retrospective study on cases notified in Peruvian residents in Florence in the
      period 2001-2010 was carried out and available Mycobacterium tuberculosis strains
      were genotyped (MIRU-VNTR-24 and Spoligotyping). One hundred thirty eight cases
      were retrieved. Genotyping performed in 87 strains revealed that 39 (44.8%)
      belonged to 12 clusters. Assuming that in each cluster the transmission of
      tuberculosis from the index case took place in Florence, a large proportion of
      cases could be preventable by improving early diagnosis of contagious cases and
      contact tracing. 

PMID- 25568759
TI  - Exertional sickling: questions and controversy.
AB  - Sickle cell trait (SCT) occurs in about 8% of African-Americans and is often
      described to be of little clinical consequence. Over time, a number of risks have
      emerged, and among these are rare but catastrophic episodes of sudden death in
      athletes and other individuals associated with physical activities which is often
      described as exercise collapse associated with sickle trait (ECAST). Despite an
      epidemiologic link between SCT and sudden death as well as numerous case reports
      in both medical literature and lay press, no clear understanding of the key
      pathophysiologic events has been identified. Strategies for identification of
      individuals at risk and prevention of ECAST have been both elusive and
      controversial. Stakeholders have advocated for different approaches to this issue
      particularly with regard to screening for hemoglobin S. Furthermore, the
      recommendations and guidelines that are in place for the early recognition of
      ECAST and the prevention and treatment of the illness are not well defined and
      remain fragmented. Among the cases identified, those in collegiate football
      players in the United States are often highlighted. This manuscript examines
      these case studies and the current recommendations to identify areas of consensus
      and controversy regarding recommendations for prevention, recognition and
      treatment of ECAST. 

PMID- 25568760
TI  - Successful Treatment of Severe Anemia using Erythropoietin in a Jehovah Witness
      with Non-Hodgkin Lymphoma.
AB  - Blood transfusion many times works in a life-saving way when a patient is facing
      a critical situation. However, some patients, such as Jehovah's Witnesses, may
      refuse their administration because it opposes to their religion beliefs. Thus,
      clinicians are forced to respect patients' preferences and seek other treatments
      in order to overcome the obstacle of the transfusion. In 1989, recombinant human
      erythropoietin (rHuEPO) was approved by the United States Food and Drug
      Administration (FDA) for the treatment of anemia associated with chronic renal
      failure. This is an amino acid glycol-protein that stimulates red blood cell
      production in the same manner as endogenous erythropoietin. Other treatment
      indications approved by the FDA include anemia due to chronic kidney disease,
      anemia secondary to zidovudine therapy in patients with human immunodeficiency
      virus infection, and anemia secondary to cancer chemotherapy. The drug also has
      been used for many off-label indications. Many Jehovah's Witnesses have accepted
      rHuEPO as a treatment option to maintain and enhance erythropoiesis. This paper
      reports the case of a 57-year-old Jehovah's Witness man, who was diagnosed with
      severe anemia due to aggressive non Hodgkin lymphoma and refused transfusion of
      blood; thanks to the treatment with rHuEPO he has managed to complete
      chemotherapy and has survived a life threatening situation. 

PMID- 25568761
TI  - The Prevalence of Transfusion Transmitted Infections in ABO Blood Groups and Rh
      Type System.
AB  - Screening of blood and blood products is important to reduce the risk of
      transfusion transmitted infections (TTIs). The transfusion of unscreened or
      inadequately screened blood and blood products are the major source of TTIs. The
      aim of this paper is to find out the prevalence of TTIs in ABO blood groups and
      Rh type system. A total of 4128 blood donors were screened from January 2010 to
      April 2014. Serological tests were performed for hepatitis B surface antigen
      (HBsAg), anti hepatitis C virus (Anti-HCV), anti HIV-1 and 2, venereal disease
      research Laboratory test (VDRL) and malaria parasite (MP) antigen. In
      seroreactive donors, HBsAg, Anti-HCV, VDRL, MP antigen and anti HIV were positive
      in 40 cases, 26 cases, 19 cases, 6 cases and 2 cases, respectively. Highest
      percentage of HBsAg, Anti HCV, VDRL, MP antigen and anti HIV was observed in
      blood group A negative (2/50), O negative (1/66), B negative (1/91), AB positive
      (2/377) blood group respectively. In the present study, the total number of
      Rhnegative donors is lower when compared to Rh-positive blood donors, but Rh
      negative blood donors show higher percentages of seroreactivity for TTIs. Larger
      scale studies at molecular level are required to improve the knowledge of this
      aspect. 

PMID- 25568762
TI  - Enteropathy-associated T cell lymphoma as a complication of silent celiac
      disease.
AB  - Celiac disease is an autoimmune disorder in which a genetic predisposition and
      the ingestion of wheat gluten triggers a deleterious immune response. This
      response is complex and may lead to manifestations other than enteropathyha:
      hepatitis, dermatitis and neuropathy. There is higher risk for neoplasia. We
      observed an atypical case, corresponding to a 69-year old female presenting with
      complicated celiac disease. The patient was referred following the histological
      examination of an enterectomy specimen, which unexpectedly revealed an
      enteropathy-associated T cell lymphoma in a background of celiac disease.
      Patient's previous medical history comprised several abdominal surgical
      procedures, without other prior symptoms suggestive of celiac disease. Indeed,
      the patient was obese and no signs of malabsortion were apparent. This case draws
      our attention to clinically silent celiac disease, which represents a diagnostic
      challenge. Thus, this should be kept in mind whenever a patient presents with
      abdominal relapsing complications, otherwise unexplained. 

PMID- 25568763
TI  - Late differentiation syndrome in acute promyelocytic leukemia: a challenging
      diagnosis.
AB  - Detailed knowledge about differentiation syndrome (DS) has remained limited.
      There are 2 large studies conducted by the Spanish workgroup PETHEMA (Programa
      Espanol de Tratamientos en Hematologia; Spanish Program on Hematology Treatments)
      and the European group trial (LPA 96-99 and APL 93) in which the incidence,
      characteristics, prognostic factors and outcome of patients developing DS are
      evaluated. Both have described the median time of DS development between 10 and
      12 days. The severity of the DS has been evaluated in the study conducted by
      PETHEMA, and severe DS usually occurs at the beginning of the treatment (median
      of 6 days), as compared with moderate DS (median of 15 days). We report here in
      two cases of late severe DS, with late diagnosis due to both time and form of
      presentation. We discuss the physiopathology, clinical presentation, prophylaxis
      and treatment of DS. 

PMID- 25568764
TI  - Discrimination of static and dynamic spectral patterns by children and young
      adults in relationship to speech perception in noise.
AB  - Past work has shown relationship between the ability to discriminate spectral
      patterns and measures of speech intelligibility. The purpose of this study was to
      investigate the ability of both children and young adults to discriminate static
      and dynamic spectral patterns, comparing performance between the two groups and
      evaluating within-group results in terms of relationship to speech-in-noise
      perception. Data were collected from normal-hearing children (age range: 5.4 -
      12.8 yrs) and young adults (mean age: 22.8 yrs) on two spectral discrimination
      tasks and speech-in-noise perception. The first discrimination task, involving
      static spectral profiles, measured the ability to detect a change in the phase of
      a low-density sinusoidal spectral ripple of wideband noise. Using dynamic
      spectral patterns, the second task determined the signal-to-noise ratio needed to
      discriminate the temporal pattern of frequency fluctuation imposed by stochastic
      low-rate frequency modulation (FM). Children performed significantly poorer than
      young adults on both discrimination tasks. For children, a significant
      correlation between speech-in-noise perception and spectral-pattern
      discrimination was obtained only with the dynamic patterns of the FM condition,
      with partial correlation suggesting that factors related to the children's age
      mediated the relationship.

PMID- 25568765
TI  - Moderate hemoptysis caused by hughes-stovin syndrome.
AB  - Hughes and Stovin first reported a syndrome consisting of multiple pulmonary
      artery aneurysms and venous thrombosis in 1959. Here, we encountered a 42-year
      old woman who had hemoptysis revealing a Hughes-Stovin syndrome. Helical computed
      tomography showed multiple pulmonary artery aneurysms with pulmonary
      thromboembolism. The patient was treated with steroid therapy, cyclophosphamide
      and anticoagulation with a good response. 

PMID- 25568766
TI  - Conservative Management of Penile Trauma may be Complicated by Abscess Formation.
AB  - Blunt penile trauma during sexual activity, although highly underreported due to
      the associated patient embarrassment, constitutes a real urological emergency
      requiring immediate attention and possibly early surgical intervention. We report
      a case of a 58-year old man who presented with penile pain following excessive
      masturbation. Although there were no clinical signs of penile deformity or
      hematoma, magnetic resonance imaging revealed the presence of a rupture in the
      tunica albuginea. The patient opted for non-surgical management and his recovery
      period was complicated by the formation of an abscess at the site of the
      albugineal tear thus prolonging his hospital stay. The abscess was surgically
      drained and the patient reports to have normal erections at 3-month follow up. 

PMID- 25568767
TI  - Pelvic neurofibroma.
AB  - A 58-year old male presented with a hard lump in lower abdomen extending into
      pelvis. Clinical examination and computed tomography scan revealed pelvic
      retroperitoneal mass. Patient underwent exploratory laparotomy - revealing a well
      encapsulated retroperitoneal mass extending up to coccyx, posterior to the
      urinary bladder. It had displaced the recto-sigmoid colon and urinary bladder to
      the right. Histopathological findings revealed a neurofibroma. Pelvic
      neurofibromas are known to arise from certain pelvic organ. However, present case
      ruled out any organ involvement both on imaging and intraoperatively. This shows
      that these tumors can arise de novo also. A brief case report and review of
      literature is presented. 

PMID- 25568768
TI  - Technique and Role of Embolization using Ethylene Vinyl-Alcohol Copolymer before
      Carotid Body Tumor Resection.
AB  - A 45-year old female referred for a large carotid body tumor resection. The tumor
      was encasing the internal (ICA) and external carotid arteries (ECA). She
      underwent angiogram and embolization of the ascending pharyngeal artery and a
      distal branch of the ECA using ethylene vinyl-alcohol copolymer (EVOH). Two days
      later, surgical resection of the tumor with regional lymph node dissection was
      performed along with an interposition reversed vein graft anastomosis between the
      mid common carotid and distal ICA. Devascularization of carotid body tumor can be
      performed using EVOH delivered through trans-arterial and percutaneous routes.
      Embolization may facilitate surgical resection and decrease blood loss but does
      not decrease the rate of neurological complications. Embolization can be
      performed by the vascular surgeon before a large carotid body tumor resection
      with minimal migration and or stroke risk. 

PMID- 25568769
TI  - Outcome of Patients with Infective Endocarditis who were Treated with
      Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy.
AB  - Infective endocarditis is a potentially life threatening condition. It is
      associated with high mortality and morbidity resulting mostly due to
      cardiorespiratory failure. Extracorporeal membrane oxygenation is a modality of
      treatment used to support hypoxic respiratory failure especially in patients who
      are already on mechanical ventilation. Continuous renal replacement therapy is
      added mainly for maintaining fluid and electrolyte balance. Here we report a case
      series of patients diagnosed with infective endocarditis who were treated with
      combined extracorporeal membrane oxygenation and continuous renal replacement
      therapy. Three patients in the age group 20-60 years were admitted with clinical
      features suggestive of infective endocarditis. During the course of hospital stay
      they developed cardiorespiratory failure requiring mechanical ventilation and
      extracorporeal membrane oxygenation support for refractory hypoxia. It was
      complicated by heart failure, renal failure and fluid overload which required
      initiation of continuous renal replacement therapy. All the three patients
      succumbed in spite of the aggressive treatment. In addition to the role played by
      each complication, delayed start of continuous renal replacement therapy might
      have also contributed to the high mortality. Early initiation of continuous renal
      replacement therapy for management of fluid overload needs to be considered in
      the management of these critically ill patients. 

PMID- 25568770
TI  - Conservative surgical approach and aesthetic management of a focal gingival
      hyperplastic lesion.
AB  - Focal reactive hyperplastic lesions of the gingiva are quite common soft tissue
      enlargements of the oral cavity. Presence of local factors, tissue irritation and
      endocrinal discrepancies contribute to its etiology. The fact that these lesions
      are caused by diverse pathological conditions and its histo-pathological
      resemblances poses a great diagnostic challenge. Due to the site predilection of
      the these lesions to the maxillary anterior region, this article presents a case
      report of focal gingival hyperplastic lesion in the anterior maxillary region and
      its conservative management leading to pleasing results and soft tissue
      esthetics. 

PMID- 25568771
TI  - Accidental intraoral formalin injection: a rare case report.
AB  - Formalin is a hazardous chemical that needs cautious handling and special
      storage. Owing to its disinfectant and fixative (i.e. for preserving pathologic
      tissue specimens in histopathology) properties, it is widely used in dentistry.
      Although, the terms formaldehyde and formalin are often confused as being
      identical, these are different as to the concentrations of the primary component
      i.e. formaldehyde. In fact, the common fixative available as 10% neutral buffered
      formalin is actually a 4% solution of formaldehyde (i.e., a 10% solution made
      from a 37-40% commercially pure formaldehyde solution). This case report
      describes an unfortunate case of accidental injection instead of local
      anesthetic, of formalin into the pterygomandibular space in a 35-year old woman
      during inferior alveolar nerve block for surgical removal of impacted lower right
      third molar and its successful management by cautious debridement (under both
      local and general anesthesia) and empirical drug therapy (utilizing analgesics
      and antibiotics). 

PMID- 25568772
TI  - Reply to: Clinical Evaluation of the Ability of a Proprietary Scoliosis Traction
      Chair to De-Rotate the Spine: 6-Month Results of Cobb Angle and Rotational
      Measurements.

PMID- 25568774
TI  - Reply to: Clinical Evaluation of the Ability of a Proprietary Scoliosis Traction
      Chair to De-Rotate the Spine: 6-Month Results of Cobb Angle and Rotational
      Measurements.

PMID- 25568773
TI  - Reply to: Clinical Evaluation of the Ability of a Proprietary Scoliosis Traction
      Chair to De-Rotate the Spine: 6-Month Results of Cobb Angle and Rotational
      Measurements.

PMID- 25568775
TI  - Reply to: Clinical Evaluation of the Ability of a Proprietary Scoliosis Traction
      Chair to De-Rotate the Spine: 6-Month Results of Cobb Angle and Rotational
      Measurements.

PMID- 25568776
TI  - Autonomic dysfunction in essential hypertension: A systematic review.
AB  - INTRODUCTION: Greater sympathetic drive has been established in the early stages
      of essential hypertension, suggesting that neurohormonal dysregulation may be key
      to its aetiology and progression. The aims of this review are to discuss evidence
      of the role of autonomic dysfunction in essential hypertension and proposed
      mechanisms, and also some applications of this knowledge to current management
      strategies of essential hypertension. METHODS: A computer search was performed
      using the PUBMED database for peer reviewed original articles comparing autonomic
      function tested via heart rate variability (HRV), muscle sympathetic nerve
      activity (MSNA) or plasma noradrenaline levels in normotensive (mean blood
      pressure (BP) of <=140/90 mmHg or <=135/85 mmHg if measured via home BP
      measurements) and hypertensive groups (mean resting BP of >=140/90 mmHg (or
      >=135/85 mmHg if measured via home BP measurements). Subjects were excluded with
      secondary causes of hypertension or autonomic dysfunction. RESULTS: A total of 17
      studies were included for discussion. The main findings of this study include
      that of reduced baroreflex sensitivity, believed to be secondary to increased
      arterial stiffness, is hypothesised to be implicated in the pathogenesis of
      essential hypertension. Also, angiotensin converting enzyme inhibitors were not
      as effective on markers of autonomic control of blood pressure when compared with
      alternative anti-hypertensive drugs. CONCLUSIONS: Consistent research is needed
      to establish the effectiveness of pharmacotherapies at each of stage of
      hypertension, and on markers of autonomic dysfunction. Consistent study designs
      will enable more accurate accumulation of data across multiple studies, and
      appropriate application of such data into clinical practice.

PMID- 25568778
TI  - From the editor.

PMID- 25568777
TI  - A survey to determine the potential impact of foundation year career aims on
      surgical specialty training.
AB  - INTRODUCTION: The competition for Core Surgical Training (CST) positions and
      subsequent Surgical Specialty Training (ST3) posts throughout the UK is fierce.
      Our aim was to conduct a pilot study to assess whether current foundation year
      doctors were considering pursuing a career in surgery and the reasons guiding
      their decisions. METHODS: A ten-item questionnaire was voluntarily completed by
      foundation doctors at a large acute teaching trust. Factors evaluated included:
      experience working within a surgical rotation; previous consideration of a career
      in surgery; whether they found a career in surgery appealing; reasons guiding
      their decision and would they be applying to CST. RESULTS: All 67 foundation
      doctors approached agreed to participate: of which 56 (83.6%) had experience
      working within a surgical rotation. Males were significantly more likely to find
      a career in surgery appealing (p < 0.001). Although 20 (29.9%) had previously
      considered a surgical career, only 11 (16.4%) would be applying to CST. Reasons
      for finding a career in surgery appealing included: job satisfaction (84.2%),
      diversity of work (79.0%) and working environment/colleagues (47.4%). Of those
      that did not consider a career in surgery to be appealing, reasons included:
      working hours (75.0%), work/life balance (62.5%), working environment/colleagues
      (50%). DISCUSSION AND CONCLUSION: Although only a small proportion of current
      foundation doctors were surveyed in our study, only 16.4% were considering
      applying for CST. These figures are lower than previously suggested and would
      indicate that there will be fewer applicants for CST in future years, which may
      potentially reduce the current bottleneck of applicants at ST3.

PMID- 25568779
TI  - Intraoperative cell salvage in revision hip surgery.
AB  - Allogenic blood is a finite resource, with associated risks. Previous studies
      show intraoperative cell salvage (ICS) can reduce allogenic transfusion rates in
      orthopaedic surgery. However, there are concerns regarding efficacy and cost
      effectiveness of ICS. This study was carried out to review ICS use in revision
      hip arthroplasty. All patients who underwent ICS and re-infusion between 2008 and
      2010 in the Southern General Hospital (SGH) were audited. The fall in haemoglobin
      (Hb), volume of blood re-infused and postoperative allogenic transfusion rates
      were recorded. This group was compared to a similar SGH cohort who underwent
      surgery by the same surgeons between 2006 and 2008, and a pre-2005 control group
      where no ICS was used. The proportion of patients receiving a postoperative
      allogenic transfusion fell by 55% in the 2008-2010 ICS cohort compared with the
      control, and by 40% compared with the previous ICS group. In both instances,
      there was a statistically significant (p < 0.001) reduction in mean units
      transfused per patient; in the 2008-2010 ICS cohort, a mean of 0.8 units was used
      per patient, while 1.4 were used in the 2006-2008 cohort. 3.5 units were used in
      the control group. There was no statistically significant difference in age or
      preoperative Hb between the groups, or in length of hospital stay. In this study,
      ICS has been shown to be effective in reducing rates and volume of postoperative
      allogenic transfusion in patients undergoing revision hip surgery at the SGH.
      However, further work is needed to establish the effect of changing anaesthetic
      technique on postoperative allogenic transfusion rates. 

PMID- 25568780
TI  - The effects of QuikClot Combat Gauze on hemorrhage control in the presence of
      hemodilution and hypothermia.
AB  - Hemorrhage is the leading cause of death from trauma. Intravenous (IV) fluid
      resuscitation in these patients may cause hemodilution and secondary hemorrhage.
      In addition, hypothermia may interfere with coagulation. The purposes of this
      study were to compare the effectiveness QuikClot Combat Gauze (QCG) to a control
      group on hemorrhage in a hemodiluted, hypothermic model, and to determine the
      effects of IV volume resuscitation on rebleeding. This was a prospective, between
      subjects, experimental design. Yorkshire swine were randomly assigned to two
      groups: QCG (n = 13) or control (n = 13). The subjects were anesthetized.
      Hypothermia (temperature of <=34.0  degrees C) was induced; 30% of their blood
      volume was exsanguinated. A 3:1 replacement of Lactated Ringer's was administered
      to dilute the remaining blood. The femoral artery and vein were transected. After
      1 min of uncontrolled hemorrhage, QCG was placed into the wound followed by
      standard wound packing. The control group underwent the same procedures without
      QCG. After 5 min of manual pressure, a pressure dressing was applied. Following
      30 min, the dressings were removed, and blood loss was calculated. For subjects
      achieving hemostasis, up to 5 L of IV fluid was administered or until bleeding
      occurred, which was defined as >2% total blood volume. The QCG had significantly
      less hemorrhage than the control (QCG = 30 +/- 99 mL; control = 404 +/- 406 mL)
      (p = .004). Further, the QCG group was able to tolerate more resuscitation fluid
      before hemorrhage (QCG = 4615 +/- 1386 mL; control = 846 +/- 1836) (p = .000). 

PMID- 25568781
TI  - Reduction in gastric cancer surgical mortality over 10 years: An adverse events
      analysis.
AB  - BACKGROUND: The reduction in gastric cancer mortality is due to a reduction in
      incidence and of surgical mortality. This study was to examine adverse events in
      patients with gastric cancer dying under surgical care. METHODS: Adverse events
      in surgical care were prospectively audited in patients who died of gastric
      cancer in Scottish hospitals. A cohort retrospective study examining deaths and
      contributing adverse events was compared for the periods 1996-2000 and 2001-2005.
      RESULTS: Between 1996 and 2005, 1083 patients with gastric cancer died on
      surgical wards in Scottish hospitals. The annual number of deaths under surgical
      care fell significantly from an average of 128 deaths per annum in years 1996
      2000 to 88 deaths per annum in 2001-2005 (p < 0.001). This occurred in parallel
      with the decline in gastric cancer incidence over the same period. There was an
      increase in the proportion of gastric cancer resections carried out in 7 major
      hospitals in Scotland in the second period of the study (p < 0.001). The mean
      number of deaths in the group of patients, who had gastric cancer resection and
      palliative surgery, were significantly lower in the second period of the study In
      addition, when all patients were considered as a group, the mean number of
      anaesthetic, critical care, medical management and technical surgery adverse
      events were significantly lower in the second study period. CONCLUSION: There has
      been a reduction in deaths and adverse events for patients with gastric cancer
      under surgical care and this has been associated with surgical subspecialisation
      in oesophago-gastric cancer surgery.

PMID- 25568782
TI  - Radio-frequency identification of surgical sponges in the abdominal cavity of
      pigs.
AB  - BACKGROUND: Counting the sponges is an important step in surgical procedures. A
      miscount may impact the patient's health, and it also has legal implications for
      the surgeon. This is an experimental study evaluating radio-frequency technology
      used in the perioperative period to identify surgical sponges left in the
      peritoneal cavity of swine. METHODS: Radio-frequency labeled-disc identification
      tags were sewn into 40 surgical towels. Twenty labels had the ability to emit
      radio-frequency waves, and 20 labels were inert to radio-frequency
      identification. Twenty adult pigs that underwent laparotomy and randomly received
      two surgical sponges were scanned by a radio-frequency identification antenna.
      RESULTS: This method presented a positive predictive value of 100% and 100%
      specificity and sensitivity, as all of the tagged surgical sponges were detected.
      CONCLUSION: Radio-frequency identification has been proved to be a useful method
      for the identification of surgical sponges within the abdominal cavities of
      swine.

PMID- 25568783
TI  - Laparoscopic versus open adrenalectomy for adrenal myelolipoma.
AB  - INTRODUCTION: Earlier reports of laparoscopic adrenalectomy (LA) for adrenal
      myelolipoma are limited. PRESENTATION OF CASE: Between June 2000 and September
      2012, we performed right adrenal resections using LA and open adrenalectomy (OA)
      in patients with myelolipoma (n = 3 and n = 3, respectively). Then, we evaluated
      patients' background characteristics and short- and long-term outcomes for both
      groups. The median maximum diameters of tumors were 3.5 (3.0-4.4) cm and 7.1 (7.0
      9.5) cm for the LA and OA groups, respectively. The median durations of the
      operation were 152 (117-188) min and 218 (153-230) min, and the median blood loss
      volumes were 50 (20-160) mL and 290 (62-1237) mL in the LA and OA groups,
      respectively. The median postoperative lengths of hospital stay were 4 (4-4) days
      and 11 (11-13) days for the LA and OA groups, respectively. Conversion from LA to
      an open approach during surgery was not necessary in any of the cases.
      Additionally, perioperative morbidity and mortality were not observed.
      DISCUSSION: The limitation of this study is its methodological design; it is a
      case series and not a matched-control study, which would be difficult to conduct
      owing to the rare nature of adrenal myelolipoma. However, we esteem that LA will
      become widespread in the future because it is feasible, cosmetic, and less
      invasive. CONCLUSION: LA was a safe, feasible, and effective approach to adrenal
      myelolipoma, assisted by advancement in preoperative imaging diagnostic
      techniques.

PMID- 25568784
TI  - Primary mucosa-associated lymphoid tissue lymphoma of the esophagus masquerading
      as a benign tumor.
AB  - We report a case of primary esophageal low-grade B-cell lymphoma of MALT type in
      a 50-year-old Saudi male patient who presented to our hospital with a history of
      dysphagia and heartburn for more than 2 years. Endoscopy showed a large
      esophageal mass with an intact mucosa located in the distal esophagus, 28 cm-35
      cm from the incisor teeth. Endoscopic ultrasonography (EUS) showed a large well
      demarcated sub-epithelial lesion 4 cm in width and 10 cm in length arising from
      the muscularis mucosa with mixed echogenicity consistent with benign leiomyoma.
      Subsequently, the patient underwent surgical resection of the tumor; the
      histopathology confirmed the diagnosis of esophageal lymphoma. The tumor was
      considered to be completely resected and therefore additional treatment was not
      administered. The patient was doing well on follow up after treatment. Clinically
      and radiologically he did not reveal any signs of recurrence. Surgical resection
      is beneficial as a primary treatment option in incipient primary low grade MALT
      esophageal lymphomas. 

PMID- 25568785
TI  - Aneurysmal degeneration and type Ib endoleak with proximal aneurysm rupture: A
      case report, review of literature and technical suggestions.
AB  - INTRODUCTION: Despite the reduction in mortality incidences of AAA in proportion
      to increased use of EVAR, the natural history of aneurysms with the presence of
      an endoleak post EVAR remains unclear. With a cumulative AAA rupture incidence of
      2% at six years post EVAR, the lack of an immediate endoleak is not an indicator
      of success. CASE REPORT: We present a case of an 80-year-old man who presented to
      the emergency department with generalised abdominal pain and hypotension. Four
      years earlier he had underwent an EVAR for a 6 cm infra-renal AAA. The computed
      tomography angiogram (CTA) illustrated aneurysmal dilatation of the left common
      iliac artery with extensive retroperitoneal haemorrhage. The patient was
      transferred to the operating room for an endovascular repair but due to
      significant episodes of haemodynamic instability, an emergency exploratory
      laparotomy was performed. To our surprise, there was a left-sided infra-renal
      anterolateral rupture of the aneurysm sac. The stent was explanted with
      difficulty from its fixed proximal aortic section down to left-sided common iliac
      artery. The fixed bare portion of the stent in the proximal aorta and in the
      right common iliac artery was left in-situ and the rest was integrated to a
      trouser graft with an end-to-end technique. DISCUSSION: On detection of an
      endoleak, the aim should focus on their endovascular management, as open
      conversions are associated with high mortality and morbidity. CONCLUSION: If open
      conversion is indicated, all technical aspects of the repair including partial
      stent extraction should be considered for best outcome.

PMID- 25568786
TI  - Multiple, persistent gastropancreato-neuroendocrine tumours accompanying sigmoid
      bowel adenocarcinoma: A rare case report.
AB  - INTRODUCTION: Gastropancreato-neuroendocrine tumours (GETs) are rare, especially
      when they occur alongside colorectal adenocarcinoma. Furthermore, multiple GETs
      occurring within the small bowel are less frequent with only two cases described
      within the literature. PRESENTATION OF CASE: A healthy 58-year old woman
      presented with severe gastrointestinal pain and faecal incontinence. Family
      history revealed consanguineous parents and a brother who had recently died of a
      gastric GET. First biopsy showed a sigmoid adenocarcinoma. Histology of the
      resected sigmoid revealed both adenocarcinoma and GET. After this, she presented
      with small bowel obstruction secondary to multiple ileal and jejunal GETs, also
      treated with resection. All imaging modalities gave no evidence of extra
      intestinal metastasis. The patient received multiple operations and chemotherapy
      but died 18 months after the original presentation. DISCUSSION: A case of such
      persistent and multiple small bowel GET without extra-intestinal metastasis has
      yet to be reported within the literature. GETs are rare and typically
      asymptomatic with a small proportion giving the classical carcinoid syndrome.
      Surgery is usually reserved for smaller GETs with high five-year survival.
      Despite this, surgery and chemotherapy were performed and both proved to be
      ineffective. Furthermore, a genetic basis for GETs is supported in this case with
      her brother suffering a similar fatal tumour. CONCLUSION: This case highlights a
      rare GET that has a likely underlying familial origin. It illustrates the non
      specific presentation of these tumours and the importance of taking a thorough
      family history. It also demonstrates that these tumours can be fatal even in the
      absence of extra-intestinal metastasis.

PMID- 25568787
TI  - Prospective therapies for high-grade glial tumours: A literature review.
AB  - After three decades of intensive research, cytoreductive surgery remains the gold
      standard of treatment of malignant gliomas. Survivorship at both 1-year and 5
      years has not drastically changed in the UK. Concomitant chemo- and radiotherapy
      has enhanced the efficiency of surgery, enabling more aggressive tumour resection
      whilst also preserving the surrounding healthy brain parenchyma. More accurate
      imaging techniques have also played a role in tumour identification, key to this
      has been pre- and intra-operative contrast enhancement and compounds that have a
      high affinity in binding to glioma cells. Intra-operative imaging has heralded
      the ability to give the operating surgeon continuous feedback to assess the
      completeness of resection. Research is shifting into investigating the complex
      cellular and molecular glial tumour-genesis, and has led to the development of
      efficacious chemotherapy agents and trial novel therapies. Oncolytic virotherapy
      has shown promise in clinical trials and gene therapy in-vitro studies. Surgery
      however remains the primary therapeutic option for the management of malignant
      gliomas removing the mass of proliferating malignant tumour cells and
      decompression of the space-occupying lesion. 

PMID- 25568788
TI  - Neostigmine for acute colonic pseudo-obstruction: A meta-analysis.
AB  - INTRODUCTION: Acute colonic pseudo-obstruction (ACPO) is an uncommon condition
      that occasionally develops in hospitalized patients with serious underlying
      ailments. Its early recognition is essential to reduce life-threatening
      complications. Few low-powered randomized clinical trials (RCTs) have confirmed
      the effectiveness of neostigmine for treatment. AIM: To analyse the effectiveness
      and main side effects of neostigmine in the treatment of ACPO. EXPERIMENTAL: A
      literature search was performed for all published RCTs, reporting on neostigmine
      as treatment for ACPO. RESULTS: Four studies fulfilled the inclusion criteria,
      evaluating 127 patients: treatment group = 65, control group = 62. Neostigmine
      effectiveness to resolve ACPO with only one dose was 89.2% versus 14.65% (P <
      0.001, NNT = 1 [95% CI 1-2]). CONCLUSIONS: Neostigmine is a safe and effective
      option for patients with ACPO who failed to respond to conservative management.

PMID- 25568789
TI  - Ventriculoperitoneal shunt and the need to remove a gallbladder: Time to
      definitely overcome the feeling that laparoscopic surgery is contraindicated.
AB  - Since Baskin et al. reported the first documented case of failure of a
      laparoscopically-induced ventriculoperitoneal shunt (VP) in 1998, the
      cerebrospinal fluid shunt has been generally considered a relative
      contraindication to laparoscopy. Although the literature is limited there is a
      small body of evidence indicating that it is safe to perform laparoscopic surgery
      on these patients with routine anaesthetic monitoring. In this study we report
      the case of a laparoscopic cholecystectomy in the presence of a
      ventriculoperitoneal shunt. A review of the literature suggests that laparoscopic
      cholecystectomy can be safely performed in patients with a ventriculoperitoneal
      shunt. The only related contraindication should be if a catheter has recently
      been placed. 

PMID- 25568790
TI  - Burkitt lymphoma involving jejunum in children.
AB  - A 5-year-old boy presented with 3-month bloody stool from unknown origin and
      progressive anemia. In this case report, we review the incidence, diagnosis,
      pathology, treatment and prognosis of Burkitt Lymphoma. 

PMID- 25568791
TI  - How grim is hepatocellular carcinoma?
AB  - Hepatocellular carcinoma (HCC) is a complex disease and a major cause of death in
      high endemic areas of hepatitis B virus (HBV) or hepatitis C virus (HCV)
      infection. HCC has gone from being a universal death sentence to a cancer that
      can be prevented, detected at an early stage and effectively treated. Liver
      resection or tumour ablation techniques may be effective bridge to liver
      transplantation if they fulfill the Milan criteria. The areas of progress in HCC
      are in the control of HBV or HCV and the development of adjuvant or neoadjuvant
      therapies. 

PMID- 25568792
TI  - The ubiquitous neural cell adhesion molecule (N-CAM).
AB  - Adhesive interactions are important for cell trafficking, differentiation,
      function and tissue differentiation. Neural cell adhesion molecule (NCAM) is
      involved in a diverse range of contact-mediated interactions among neurons,
      astrocytes, oligodendrocytes, and myotubes. It is widely but transiently
      expressed in many tissues early in embryogenesis. Four main isoforms exist but
      there are many other variants resulting from alternative splicing and post
      translational modifications. This review discusses the actions and association of
      N-CAM and variants, PSA CAM. L1CAM and receptor tyrosine kinase. Their
      interactions with the interstitial cells of Cajal - the pacemaker cells of the
      gut in the manifestation of gut motility disorders, expression in carcinomas and
      mesenchymal tumours are discussed. 

PMID- 25568793
TI  - No-drain mastectomy - Preventing seroma using TissuGlu((r)): A small case series.
AB  - INTRODUCTION: Post-mastectomy seroma, with an occurrence of up to 59%, is a major
      complication in modern oncological surgery. While drain placement is a common
      tool in dealing with this complication, some patients may either be incapable or
      unwilling to accept this course of action, requiring an alternative option for
      seroma prevention. A recent study using a lysine-derived urethane adhesive named
      TissuGlu((r)) has shown promising results in mastectomy patients. CASE
      PRESENTATION: We used TissuGlu((r)) in three patients who could not have a post
      operative drain after mastectomy due to a variety of reasons. Standard mastectomy
      protocols were followed. Two no-drain mastectomy patients did not show any post
      operative seroma formation (cases 1 and 2), while a third patient had to be
      aspirated twice at two (180 ml) and four weeks (60 ml) post-surgery. No
      complications such as hematoma, wound dehiscence or adverse reactions to the
      adhesive were observed. Patient satisfaction with the no-drain situation was high
      as post-surgical discomfort was minimal. CONCLUSION: Although one patient
      developed small amounts of seroma, TissuGlu((r)) may present an additional option
      in the high risk, no-drain post-mastectomy scenario.

PMID- 25568794
TI  - Antibiotic management of complicated intra-abdominal infections in adults: The
      Asian perspective.
AB  - Regional epidemiological data and resistance profiles are essential for selecting
      appropriate antibiotic therapy for intra-abdominal infections (IAIs). However,
      such information may not be readily available in many areas of Asia and current
      international guidelines on antibiotic therapy for IAIs are for Western
      countries, with the most recent guidance for the Asian region dating from 2007.
      Therefore, the Asian Consensus Taskforce on Complicated Intra-Abdominal
      Infections (ACT-cIAI) was convened to develop updated recommendations for
      antibiotic management of complicated IAIs (cIAIs) in Asia. This review article is
      based on a thorough literature review of Asian and international publications
      related to clinical management, epidemiology, microbiology, and bacterial
      resistance patterns in cIAIs, combined with the expert consensus of the Taskforce
      members. The microbiological profiles of IAIs in the Asian region are outlined
      and compared with Western data, and the latest available data on antimicrobial
      resistance in key pathogens causing IAIs in Asia is presented. From this
      information, antimicrobial therapies suitable for treating cIAIs in patients in
      Asian settings are proposed in the hope that guidance relevant to Asian practices
      will prove beneficial to local physicians managing IAIs. 

PMID- 25568795
TI  - Perioperative management in order to minimise postoperative delirium and
      postoperative cognitive dysfunction: Results from a Swedish web-based survey.
AB  - Cognitive side-effects such as emergence agitation (EA), postoperative delirium
      (POD) and postoperative cognitive dysfunction (POCD) are not infrequently
      complicating the postoperative care especially in elderly and fragile patients.
      The aim of the present survey was to gain insight regarding concern and interest
      in prevention and treatment strategies for postoperative delirium and
      dysfunction, and the use of EEG-based depth-of-anaesthesia monitoring possibly
      reducing the risk for cognitive side effects among anaesthesia personnel.
      METHODS: A web-based validated questionnaire was sent to all Swedish
      anaesthesiologists and nurse anaesthetists during summer 2013. The questionnaire
      consisted of 3 sections, subjective preferences, routines and practices related
      to the perioperative handling of EA, POD, POCD. RESULTS: The response rate was
      52%. Cardiovascular/pulmonary risks where assessed as importance by 98, 97% of
      responders while 69% considered the risk of neurocognitive side-effects
      important. When asked explicitly around cognitive side-effects 89%, 37% and 44%
      assessed awareness, POC and POD respectively of importance. EEG-based depth-of
      anaesthesia monitors were used in 50% of hospitals. The responders were not
      convinced about the benefits of such monitors even in at-risk patients.
      Structured protocols for the management of postoperative cognitive side-effects
      were available only in few hospitals. CONCLUSION: Swedish anaesthesia personnel
      are concerned about the risk of postoperative cognitive side-effects but are more
      concerned about cardiovascular/pulmonary risks, pain, PONV and the rare event of
      awareness. Most respondents were not convinced about the use of depth-of
      anaesthesia monitors. There is a need to improve knowledge around risk factors,
      prevention and management of postoperative cognitive side effects.

PMID- 25568796
TI  - The history of monoclonal antibody development - Progress, remaining challenges
      and future innovations.
AB  - As medicine progresses into a new era of personalised therapy, the use of
      monoclonal antibodies to treat a wide range of diseases lies at the heart of this
      new forefront. Since the licencing of the first monoclonal antibody for clinical
      use 30 years ago, the monoclonal antibody industry has expanded exponentially and
      is now valued at billions of dollars. With major advances in genetic sequencing
      and biomedical research, much research into monoclonal antibodies now focuses on
      identifying new targets for development and maximising their efficacy for use in
      clinical practice. However, a balance has to be struck with regards to reducing
      numbers of side-effects and overall economic cost, which arguably somewhat
      blighted their early clinical and commercial successes. Nowadays, there are
      approximately 30 monoclonal antibodies that have been approved for use in
      clinical practice with many more currently being tested in clinical trials. Some
      of the current major limitations include: the use of inefficient models for
      generation, a lack of efficacy and issues of cost-effectiveness. Some of the
      current research focuses on ways to improve the efficacy of existing monoclonal
      antibodies through optimising their effects and the addition of beneficial
      modifications. This review will focus on the history of monoclonal antibody
      development - how it has increasingly moved away from using laborious animal
      models to a more effective phage display system, some of the major drawbacks from
      a clinical and economical point of view and future innovations that are currently
      being researched to maximise their effectiveness for future clinical use. 

PMID- 25568797
TI  - A porcelain gallbladder and a rapid tumor dissemination.
AB  - INTRODUCTION: Porcelain gallbladder is a very rare entity that consists of a
      calcification of the gallbladder wall, and is associated with carcinoma in 12.5
      62% of patients, although recent studies suggest weaker association. CASE REPORT:
      We describe an 80-year-old woman who presented with colicky abdominal pain in the
      right upper quadrant, radiating to the back and associated with vomiting.
      Physical examination revealed jaundice, murphy's sign was negative. Hepatic
      biliary tract ultrasound revealed porcelain gallbladder, she was referred to the
      surgical team for a scheduled cholecystectomy. A month later, she presented
      diffuse abdominal pain. Imaging studies showed a disseminated process affecting
      liver's segments, capsule, and hilum; and lungs. An aggressive surgical treatment
      was dismissed, and was referred to the oncology department. DISCUSSION: There is
      controversy in the harboring risk of malignancy of the porcelain gallbladder.
      While it seems that the current data points towards a lower risk of degeneration,
      it is also demonstrated that patients with gallbladder wall calcifications are
      indeed statistically at risk of gallbladder cancer. Laparoscopic cholecystectomy
      has become a safe and efficient approach recommended for patients with
      gallbladder symptoms directly related or unrelated to gallbladder wall
      calcifications. In this case, a pathological gallbladder, very quickly evolved
      into an inoperable tumor with a poor prognosis. CONCLUSION: This report heightens
      that with US evidence of porcelain gallbladder, an urgent CT scan should be
      carried out to assess an underlying malignancy, and a simple cholecystectomy
      should be done urgently rather than on a routine elective list to prevent
      possible malignant change if possible.

PMID- 25568798
TI  - Enterocolic fistula due to a rectal stent: Case report and literature review.
AB  - INTRODUCTION: Self-expanding metal stents (SEMS) are successfully being used to
      acutely relieve obstructing colorectal cancers; yet, their use does not come
      without complications. PRESENTATION OF CASE: We present a case in which a patient
      with a recurrent obstructing sigmoid carcinoma underwent colonic stenting for
      acute decompression. Two months after stent placement, an enterocolic fistula
      formed from erosion of the upper end of the stent. DISCUSSION: An extensive
      literature review revealed that fistula formation, as a complication of stent
      placement, is rarely reported. Presentation of the case is followed by a review
      of complications that may arise following SEMS placement, with a focus on
      enterocolic fistulae. To our knowledge, this work provides the most extensive
      review of the subject to date. CONCLUSION: SEMS provide an effective, safe, and
      less invasive option for patients when used in the appropriate clinical context.
      Further reports of enterocolic fistulae as a complication of SEMS placement are
      necessary in order to better understand this potential adverse event.

PMID- 25568799
TI  - Invasive procedures with questionable indications.
AB  - Insufficient coordination of medical research and partial isolation from the
      international scientific community can result in application of invasive methods
      without sufficient indications. Here is presented an overview of renal and
      pancreatic biopsy studies performed in the course of the operations of pancreatic
      blood shunting into the systemic blood flow in type 1 diabetic patients.
      Furthermore a surgical procedure of lung denervation as a treatment method of
      asthma as well as the use of bronchoscopy for research in asthmatics are
      discussed here. Today, the upturn in Russian economy enables acquisition of
      modern equipment; and medical research is on the increase. Under these
      circumstances, the purpose of this letter was to remind that, performing surgical
      or other invasive procedures, the risk-to-benefit ratio should be kept as low as
      possible. 

PMID- 25568800
TI  - Surgical treatment of hepatic echinococcosis in Prizren (Kosovo).
AB  - Management option of hepatic echinococcosis represents a major challenge for a
      surgeon. The aim of the study was to evaluate surgical treatment of patients with
      hepatic echinococcosis at the surgery department of the regional hospital in
      Prizren (Kosovo). The medical records of 22 patients operated for hepatic
      echinococcosis in our department during a four year study period (2009-2013) were
      retrospectively reviewed. Apart from the total of 5850 operated patients, 22
      cases were diagnosed for liver echinococcosis (0.4%). The most affected age group
      was from 26 to 50 years (54.5%). Female gender, 16 cases (73%), and patients
      living in rural places, 14 patients (64%), dominated significantly. The most
      affected region was Municipality of Dragash. All patients underwent
      ultrasonography, 13 patients underwent CT scans and 5 patients MRI of abdomen.
      The mean preoperative ultrasonographic diameter of cysts was 9.5 cm and maximal
      21 cm. Cysts were most often localized in right hepatic lobe (77%) and subcostal
      laparotomy was most commonly performed (82%). The performed surgical procedures
      were: endocystectomy and partial pericystectomy with omentoplication according to
      Papadimitris (73%), endocystectomy and capitonnage and endocystectomy with
      external drainage (14%). The laparoscopic approach was used only in one patient.
      In conclusion, hepatic echinococosis was not common among operated patients at
      our surgery department. Subcostal laparotomy with endocystectomy and partial
      pericystectomy with omentoplication according to Papadimitris was most commonly
      used. Exact distribution of echinococcosis is needed to be analyzed with a larger
      cohort study including all surgery units in the country and with a longer
      monitoring. 

PMID- 25568801
TI  - Adhesional omental hernia: A case report.
AB  - INTRODUCTION: Omental hernias are rare and difficult to diagnose preoperatively
      due to a lack of specific symptoms. PRESENTATION OF CASE: We report a case of
      adhesional omental hernia diagnosed at laparoscopy. A 38 year-old female patient
      with evidence of a previous caesarean section presented with an acute abdomen. We
      found there were omental bands stuck onto the anterior wall of the uterus, and a
      loop of small bowel passing through the subsequent omental defect was dilated
      proximally without oedema. We performed laparoscopic exploration. We saw that
      there were omental bands stuck onto the anterior wall of the uterus, this was
      partially narrowing a segment of ileum. We also saw that the proximal bowel loop
      occupying the omental defect was dilated without oedema. CONCLUSION: This is an
      uncommon cause of an acute abdomen, but should be kept in mind as a differential
      diagnosis, especially in patients with a surgical history.

PMID- 25568802
TI  - Ligation of superior mesenteric vein and portal to splenic vein anastomosis after
      superior mesenteric-portal vein confluence resection during
      pancreaticoduodenectomy - Case report.
AB  - 62 year old Caucasian female with pancreatic head mass abutting the superior
      mesenteric vein (SMV) presented with fine needle aspiration biopsy confirmed
      diagnosis of ductal adenocarcinoma. CT scan showed near complete obstruction of
      portal vein and large SMV collateral development. After 3 months of neoadjuvant
      therapy, her portal vein flow improved significantly, SMV collateral circulation
      was diminished. Pancreaticoduodenectomy (PD) and superior mesenteric portal vein
      (SMPV) confluence resection were performed; A saphenous vein interposition graft
      thrombosed immediately. The splenic vein remnant was distended and adjacent to
      the stump of the portal vein. Harvesting an internal jugular vein graft required
      extra time and using a synthetic graft posed a risk of graft thrombosis or
      infection. As a result, we chose to perform a direct anastomosis of the portal
      and splenic vein in a desperate situation. The anastomosis decompressed the
      mesenteric venous system, so we then ligated the SMV. The patient had an
      uneventful postoperative course, except transient ascites. She redeveloped
      ascites more than one year later. At that time a PET scan showed bilateral lung
      and right femur metastatic disease. She expired 15 months after PD. CONCLUSION:
      The lessons we learned are (1) Before SMPV confluence resection, internal jugular
      vein graft should be ready for reconstruction. (2) Synthetic graft is an
      alternative for internal jugular vein graft. (3) Direct portal vein to SMV
      anastomosis can be achieved by mobilizing liver. (4) It is possible that venous
      collaterals secondary to SMV tumor obstruction may have allowed this patient's
      post-operative survival.

PMID- 25568803
TI  - C-arm rotation as a method for reducing peak skin dose in interventional
      cardiology.
AB  - PURPOSE: Prolonged interventional cardiology (IC) procedures may result in
      radiation-induced skin injury, a potentially preventable cause of patient
      morbidity. Rotating the C-arm during an IC procedure may reduce this risk,
      although the methods by which the technique can be practically applied remains
      unexplored. A previous study demonstrated that C-arm rotation often increases
      peak skin dose (PSD) in interventional radiology procedures. The purpose of this
      study was to determine whether C-arm rotation reduces the PSD in IC procedures
      and, if so, under what circumstances. MATERIALS AND METHODS: Simulations were
      performed using a numerical ray-tracing algorithm to analyse the effect of C-arm
      rotation on PSD across a range of patient sizes, C-arm configurations and
      procedure types. Specific data from modern fluoroscopes and patient dimensions
      were used as inputs to the simulations. RESULTS: In many cases, modest C-arm
      rotation angles completely eliminated overlap between X-ray field sites on the
      skin. When overlap remained, PSD increases were generally small. One exception
      was craniocaudal rotation, which tended to increase PSD. C-arm rotation was most
      effective for large patients and small X-ray field sizes. Small patients may not
      benefit from C-arm rotation as a procedural modification. The use of a
      prophylactic method where the C-arm was rotated between small opposing oblique
      angles was effective in reducing PSD. CONCLUSIONS: With the exception of rotation
      to steep craniocaudal angles, rotating the C-arm reduces PSD in IC procedures
      when used as either a procedural modification or a prophylactic strategy. Tight
      collimation increases the benefit of C-arm rotation.

PMID- 25568805
TI  - A tribute to Dr. Per-Ingvar Branemark.

PMID- 25568804
TI  - Endophenotypes for Age-Related Macular Degeneration: Extending Our Reach into the
      Preclinical Stages of Disease.
AB  - The key to reducing the individual and societal burden of age-related macular
      degeneration (AMD)-related vision loss, is to be able to initiate therapies that
      slow or halt the progression at a point that will yield the maximum benefit while
      minimizing personal risk and cost. There is a critical need to find clinical
      markers that, when combined with the specificity of genetic testing, will
      identify individuals at the earliest stages of AMD who would benefit from
      preventive therapies. These clinical markers are endophenotypes for AMD, present
      in those who are likely to develop AMD, as well as in those who have clinical
      evidence of AMD. Clinical characteristics associated with AMD may also be
      possible endophenotypes if they can be detected before or at the earliest stages
      of the condition, but we and others have shown that this may not always be valid.
      Several studies have suggested that dynamic changes in rhodopsin regeneration
      (dark adaptation kinetics and/or critical flicker fusion frequencies) may be more
      subtle indicators of AMD-associated early retinal dysfunction. One can test for
      the relevance of these measures using genetic risk profiles based on known
      genetic risk variants. These functional measures may improve the sensitivity and
      specificity of predictive models for AMD and may also serve to delineate clinical
      subtypes of AMD that may differ with respect to prognosis and treatment. 

PMID- 25568806
TI  - N-acetylcysteine and the human serum components that inhibit bacterial invasion
      of gingival epithelial cells prevent experimental periodontitis in mice.
AB  - PURPOSE: We previously reported that human serum significantly reduces the
      invasion of various oral bacterial species into gingival epithelial cells in
      vitro. The aims of the present study were to characterize the serum component(s)
      responsible for the inhibition of bacterial invasion of epithelial cells and to
      examine their effect on periodontitis induced in mice. METHODS: Immortalized
      human gingival epithelial (HOK-16B) cells were infected with various 5- (and 6-)
      carboxy-fluorescein diacetate succinimidyl ester-labeled oral bacteria, including
      Fusobacterium nucleatum, Provetella intermedia, Porphyromonas gingivalis, and
      Treponiema denticola, in the absence or presence of three major serum components
      (human serum albumin [HSA], pooled human IgG [phIgG] and alpha1-antitrypsin).
      Bacterial adhesion and invasion were determined by flow cytometry. The levels of
      intracellular reactive oxygen species (ROS) and activation of small GTPases were
      examined. Experimental periodontitis was induced by oral inoculation of P.
      gingivalis and T. denticola in Balb/c mice. RESULTS: HSA and phIgG, but not
      alpha1-antitrypsin, efficiently inhibited the invasion of various oral bacterial
      species into HOK-16B cells. HSA but not phIgG decreased the adhesion of F.
      nucleatum onto host cells and the levels of intracellular ROS in HOK-16B cells. N
      acetylcysteine (NAC), a ROS scavenger, decreased both the levels of intracellular
      ROS and invasion of F. nucleatum into HOK-16B cells, confirming the role of ROS
      in bacterial invasion. Infection with F. nucleatum activated Rac1, a regulator of
      actin cytoskeleton dynamics. Not only HSA and NAC but also phIgG decreased the F.
      nucleatum-induced activation of Rac1. Furthermore, both HSA plus phIgG and NAC
      significantly reduced the alveolar bone loss in the experimental periodontitis
      induced by P. gingivalis and T. denticola in mice. CONCLUSIONS: NAC and the serum
      components HSA and phIgG, which inhibit bacterial invasion of oral epithelial
      cells in vitro, can successfully prevent experimental periodontitis.

PMID- 25568807
TI  - Association between immunoglobulin G1 against Tannerella forsythia and reduction
      in the loss of attachment tissue.
AB  - PURPOSE: To evaluate whether the levels of immunoglobulin G (IgG) antibody to
      Tanerella forsythia are associated with periodontal status. METHODS: Patients
      with a diagnosis of chronic periodontitis were considered candidates for the
      study; thus 80 chronic periodontitis patients and 28 healthy persons (control
      group) were invited to participate in this investigation. The presence of T.
      forsythia was detected by polymerase chain reaction (PCR) analysis using primers
      designed to target the respective 16S rRNA gene sequences. Peripheral blood was
      collected from each subject to identify the IgG1 and IgG2 serum antibodies
      against T. forsythia. All microbiological and immunological laboratory processes
      were completed blindly, without awareness of the clinical status of the study
      patients or of the periodontal sites tested. RESULTS: The bivariate analysis
      showed that lower mean levels of clinical attachment level (CAL) and probing
      depth were found in the presence of the IgG1 antibody titers against whole-cell
      T. forsythia; however, only the difference in CAL was statistically significant.
      In the presence of the IgG2 antibody titers against whole-cell T. forsythia, the
      periodontal parameters evaluated were higher but they did not show statistical
      differences, except for plaque. The unadjusted linear regression model showed
      that the IgG1 antibody against whole-cell T. forsythia in periodontitis patients
      was associated with a lower mean CAL (beta=-0.654; 95% confidence interval [CI], 
      1.27 to -0.28; P<0.05). This statistically significant association remained after
      adjusting for possible confounders (beta=-0.655; 95% CI, -1.28 to -0.29; P<0.05).
      On the other hand, smoking was a statistically significant risk factor in the
      model (beta=0.704; 95% CI, 0.24 to 1.38; P<0.05). CONCLUSIONS: Significantly
      lower mean levels of CAL were shown in the presence of the IgG1 antibody titers
      against whole-cell T. forsythia in periodontitis patients. Thus, the results of
      this study suggest that IgG1 antibody to T. forsythia may have been a protective
      factor from periodontitis in this sample.

PMID- 25568808
TI  - Effects of adjunctive daily phototherapy on chronic periodontitis: a randomized
      single-blind controlled trial.
AB  - PURPOSE: The purpose of this randomized single-blind controlled trial was to
      elucidate the clinical and antimicrobial effects of daily phototherapy (PT) as an
      adjunct to scaling and root planing (SRP) in patients with chronic periodontitis.
      METHODS: The study was conducted from December 2013 to May 2014 at Ewha Womans
      University Mokdong Hospital, Seoul, Korea. Forty-one patients with mild to
      moderate chronic periodontitis were randomly divided into two therapeutic groups
      in a 1:1 ratio: SRP+PT and SRP (control) groups. All participants underwent full
      mouth SRP. PT was performed thrice a day for a month by using electric
      toothbrushes with embedded light-emitting diodes. Plaque index, gingival index,
      probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on
      probing were assessed before (baseline) and four weeks after (follow-up) the
      treatment. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis,
      Tannerella forsythia, Treponema denticola, Prevotella intermedia, Fusobacterium
      nucleatum, Parvimonas micra, Campylobacter rectus, Eikenella corrodens,
      Streptococcus mutans, and Streptococcus sobrinus levels were detected by a real
      time polymerase chain reaction at the same points in time. RESULTS: The clinical
      parameters improved in both the groups. At the follow-up assessment, PPD was
      significantly decreased in the SRP+PT group (P=0.00). Further, PPD and CAL showed
      significantly greater changes in the SRP+PT group than in the SRP group (PPD,
      P=0.03; CAL, P=0.04). P. gingivalis and T. forsythia levels decreased in this
      group, but no significant intergroup differences were noted. CONCLUSIONS:
      Adjunctive PT seems to have clinical benefits, but evidence of its antimicrobial
      effects is not sufficient. Long-term studies are necessary to develop the most
      effective PT protocol and compare the effectiveness of PT with and without
      exogenous photosensitizers.

PMID- 25568809
TI  - Statistical methods used in articles published by the Journal of Periodontal and
      Implant Science.
AB  - PURPOSE: The purposes of this study were to assess the trend of use of
      statistical methods including parametric and nonparametric methods and to
      evaluate the use of complex statistical methodology in recent periodontal
      studies. METHODS: This study analyzed 123 articles published in the Journal of
      Periodontal & Implant Science (JPIS) between 2010 and 2014. Frequencies and
      percentages were calculated according to the number of statistical methods used,
      the type of statistical method applied, and the type of statistical software
      used. RESULTS: Most of the published articles considered (64.4%) used statistical
      methods. Since 2011, the percentage of JPIS articles using statistics has
      increased. On the basis of multiple counting, we found that the percentage of
      studies in JPIS using parametric methods was 61.1%. Further, complex statistical
      methods were applied in only 6 of the published studies (5.0%), and nonparametric
      statistical methods were applied in 77 of the published studies (38.9% of a total
      of 198 studies considered). CONCLUSIONS: We found an increasing trend towards the
      application of statistical methods and nonparametric methods in recent
      periodontal studies and thus, concluded that increased use of complex statistical
      methodology might be preferred by the researchers in the fields of study covered
      by JPIS.

PMID- 25568810
TI  - Oral signs of acute leukemia for early detection.
AB  - PURPOSE: Systemic disease can manifest oral signs at an early phase, which may be
      crucial for the diagnosis and timing of treatment. This report describes two
      patients who presented with gingival enlargement as an early sign of acute
      leukemia. METHODS: Two patients presented with oral symptoms including severe
      gingival enlargement. The progress of their symptoms was associated with
      underlying systemic disease. RESULTS: The patients were transferred to the
      Department of Hematology and diagnosed with acute myelomonocytic leukemia. They
      received appropriate treatment and survived. CONCLUSIONS: Gingival enlargement
      can be caused by underlying systemic diseases. Accurate diagnosis and timely
      referral are important for preventing a fatal situation. It must be emphasized
      that some oral signs and symptoms may be closely correlated with systemic
      diseases.

PMID- 25568811
TI  - Root coverage with a modified laterally positioned flap combined with a
      subepithelial connective tissue graft in advanced recession.
AB  - PURPOSE: A laterally positioned flap (LPF) combined with a subepithelial
      connective tissue graft (SCTG) is one of the conventional approaches for
      resolving gingival recession defects, with the advantages of flap flexibility and
      extended coverage of the tissue graft. However, thus far, evidence is lacking for
      the use of this technique for the treatment of advanced gingival recession
      defects. This report discusses three Miller class III cases with interproximal
      bone loss and wide and deep defects treated with a combination procedure of a
      modified laterally positioned flap (mLPF) and SCTG. METHODS: mLPF combined with
      SCTG was performed for each case. The defect size and the degree of
      hypersensitivity at baseline and the final appointment in each case were
      documented. RESULTS: The three cases had a mean initial defect of 7.7+/-1.5 mm
      and a mean residual defect of 1.7+/-1 mm at the 6-, 3-, and 36-month follow-up,
      respectively, after the root coverage surgery. The symptom of hypersensitivity
      was improved, and the patients were satisfied with the clinical outcomes.
      CONCLUSIONS: The results demonstrated that the combination of mLPF with SCTG is
      promising for treating these advanced cases with respect to obtaining the
      expected root coverage with the gingival tissue.

PMID- 25568812
TI  - Rapid and Sensitive Detection of p53 Based on DNA-Protein Binding Interactions
      Using Silver Nanoparticle Films and Microwave Heating.
AB  - Tumor detection can be carried out via the detection of proteins, such as p53,
      which is known to play vital role in more than 50% of all cancers affecting
      humans. Early diagnosis of tumor detection can be achieved by decreasing the
      lower detection limit of p53 bioassays. Microwave-accelerated bioassay (MAB)
      technique, which is based on the use of circular bioassay platforms in
      combination with microwave heating, is employed for the rapid and sensitive
      detection of p53 protein. Direct sandwich ELISA was constructed on our circular
      bioassay platforms based on DNA-protein binding interactions. Colorimetric and
      fluorescence based detection methods were used for room temperature bioassay
      (control bioassay; total bioassay time is 27 hours) and bioassay using microwave
      heating (i.e., the MAB technique; total bioassay time is 10 minutes). In the
      colorimetric based detection, a very high background signal due to the non
      specific binding of proteins for the bioassay carried out at room temperature and
      a LLOD of 0.01 ng/mL for p53 was observed using the MAB technique. The LLOD for
      the fluorescence-based detection using the MAB technique was found to be 0.01
      ng/mL. The use of circular bioassay platforms in the MAB technique results in
      microwave-induced temperature gradient, where the specific protein binding
      interactions are significantly accelerated; thereby reducing the background
      signal and the lower limit of detection of p53 protein.

PMID- 25568813
TI  - Circular Bioassay Platforms for Applications in Microwave-Accelerated Techniques.
AB  - In this paper, we present the design of four different circular bioassay
      platforms, which are suitable for homogeneous microwave heating, using
      theoretical calculations (i.e., COMSOLTM multiphysics software). Circular
      bioassay platforms are constructed from poly(methyl methacrylate) (PMMA) for
      optical transparency between 400-800 nm, has multiple sample capacity (12, 16, 19
      and 21 wells) and modified with silver nanoparticle films (SNFs) to be used in
      microwave-accelerated bioassays (MABs). In addition, a small monomode microwave
      cavity, which can be operated with an external microwave generator (100 W), for
      use with the bioassay platforms in MABs is also developed. Our design parameters
      for the circular bioassay platforms and monomode microwave cavity during
      microwave heating were: (i) temperature profiles, (ii) electric field
      distributions, (iii) location of the circular bioassay platforms inside the
      microwave cavity, and (iv) design and number of wells on the circular bioassay
      platforms. We have also carried out additional simulations to assess the use of
      circular bioassay platforms in a conventional kitchen microwave oven (e.g., 900
      W). Our results show that the location of the circular bioassay platforms in the
      microwave cavity was predicted to have a significant effect on the homogeneous
      heating of these platforms. The 21-well circular bioassay platform design in our
      monomode microwave cavity was predicted to offer a homogeneous heating pattern,
      where inter-well temperature was observed to be in between 23.72-24.13 degrees C
      and intra-well temperature difference was less than 0.21 degrees C for 60 seconds
      of microwave heating, which was also verified experimentally.

PMID- 25568814
TI  - Examining Gender Inequality In A High School Engineering Course.
AB  - This paper examines gender inequality within the context of an upper-level high
      school engineering course recently offered in Texas. Data was collected from six
      high schools that serve students from a variety of backgrounds. Among the almost
      two hundred students who enrolled in this challenge-based engineering course,
      females constituted a clear minority, comprising only a total of 14% of students.
      Quantitative analyses of surveys administered at the beginning of the school year
      (Fall 2011) revealed statistically significant gender gaps in personal attitudes
      towards engineering and perceptions of engineering climate. Specifically, we
      found that compared to males, females reported lower interest in and intrinsic
      value for engineering, and expressed less confidence in their engineering skills.
      Additionally, female students felt that the classroom was less inclusive and
      viewed engineering occupations as less progressive. Gender disparities on all of
      these measures did not significantly decrease by the end of the school year
      (Spring 2012). Findings suggest that efforts to increase the representation of
      women in the engineering pipeline via increasing exposure in secondary education
      must contend not only with obstacles to recruiting high school girls into
      engineering courses, but must also work to remedy gender differences in
      engineering attitudes within the classroom.

PMID- 25568815
TI  - Are Periventricular Lesions Specific for Multiple Sclerosis?
AB  - BACKGROUND: The presence of periventricular lesions (PVL) on MRI scans is part of
      the revised McDonald multiple sclerosis (MS) diagnostic criteria. However, PVL
      can be found in other neurological diseases including stroke and migraine.
      Migraine is highly prevalent in patients with MS. OBJECTIVE: To determine if PVL
      are specific for patients with MS compared to stroke and migraine. METHODS: We
      studied patients diagnosed with clinically isolated syndrome (CIS), relapsing
      remitting MS (RRMS), migraine, and ischemic stroke. The number, location and the
      volume of PVL were identified on brain MRI scans and analyzed. RESULTS: The
      number and volume of PVL adjacent to the body and the posterior horn of the
      lateral ventricles were significantly increased on fluid-attenuated inversion
      recovery MRI in RRMS compared to migraine. There were no significant differences
      in the total number and volume of PVL in ischemic stroke patients compared to the
      age-matched RRMS patients nor in the number and volume of PVL adjacent to the
      anterior and temporal horns of the lateral ventricles on FLAIR images in migraine
      compared to CIS or RRMS. CONCLUSION: In contrast to PVL adjacent to the body and
      the posterior horn of the lateral ventricles, PVL adjacent to the anterior and
      temporal horns of the lateral ventricles may not be specific for CIS/RRMS when
      compared to migraine, the disease highly prevalent among patients with MS. PVL
      are not specific for MS when compared to ischemic stroke.

PMID- 25568817
TI  - Bleeding risks associated with herbal medicine in children.

PMID- 25568816
TI  - Acute Immunotoxic Effects of Perfluorononanoic Acid (PFNA) in C57BL/6 Mice.
AB  - otrganic perfluorochemicals (PFCs) have become an environmental concern due to
      widespread detection in human blood and experimental evidence for immune,
      developmental, and liver toxicity. Whereas the blood concentrations of many PFCs
      are declining, blood levels of Perfluorononanoic Acid (PFNA) are rising in the
      United States. The purpose of the present studies was to determine the effects of
      PFNA on lymphoid organs and immune cells of C57BL/6 mice. The present study
      demonstrates that PFNA produces immunotoxic effects in both male and female
      C57BL/6 mice as evidenced by splenic atrophy, decreased splenocyte numbers, and a
      marked reduction in thymocyte viability. The current study also demonstrates that
      the effects of PFNA on different leukocyte populations are not uniform. The
      CD4+CD8+ double-positive thymocytes were particularly sensitive to PFNA in which
      the proportion of this population was >95% decreased relative to the entire CD4+
      thymocyte population in PFNA-treated mice. Interestingly, PFNA also markedly
      increased serum levels of TNFalpha in response to LPS in mice. Collectively, the
      present studies demonstrate that PFNA decreases lymphocyte viability and alters
      the immune response to LPS in C57BL/6 mice.

PMID- 25568818
TI  - Global advances toward a whole systems approach.

PMID- 25568819
TI  - Peace corps partnered health services implementation research in global health:
      opportunity for impact.
AB  - BACKGROUND: There is abundant evidence of the affordable, life-saving
      interventions effective at the local primary health care level in low- and middle
      income countries (LMICs). However, the understanding of how to deliver those
      interventions in diverse settings is limited. Primary healthcare services
      implementation research is needed to elucidate the contextual factors that can
      influence the outcomes of interventions, especially at the local level. US
      universities commonly collaborate with LMIC universities, communities, and health
      system partners for health services research but common barriers exist. Current
      challenges include the capacity to establish an ongoing presence in local
      settings in order to facilitate close collaboration and communication. The Peace
      Corps is an established development organization currently aligned with local
      health services in many LMICs and is well-positioned to facilitate research
      partnerships. This article explores the potential of a community-Peace Corps
      academic partnership approach to conduct local primary healthcare services
      implementation research. DISCUSSION: The Peace Corps is well positioned to offer
      insights into local contextual factors because volunteers work closely with local
      leaders, have extensive trust within local communities, and have an ongoing,
      constant, well-integrated presence. However, the Peace Corps does not routinely
      conduct primary healthcare services implementation research. Universities, within
      the United States and locally, could benefit from the established resources and
      trust of the Peace Corps to conduct health services implementation research to
      advance access to local health services and further the knowledge of real world
      application of local health services in a diversity of settings. The proposed
      partnership would consist of (1) a local community advisory board and local
      health system leaders, (2) Peace Corps volunteers, and (3) a US-LMIC academic
      institutional collaboration. Within the proposed partnership approach, the
      contributions of each partner are as follows: the local community and health
      system leadership guides the work in consideration of local priorities and
      context; the Peace Corps provides logistical support, community expertise, and
      local trust; and the academic institutions offer professional technical and
      public health educational and training resources and research support.
      CONCLUSION: The Peace Corps offers the opportunity to enhance a community
      academic partnership in LMICs through community-level guidance, logistical
      assistance, and research support for community based participatory primary health
      care services implementation research that addresses local primary healthcare
      priorities.

PMID- 25568820
TI  - Serial case reporting yoga for idiopathic and degenerative scoliosis.
AB  - BACKGROUND: Non-surgical techniques for treating scoliosis frequently focus on
      realigning the spine, typically by muscular relaxation or muscular or ligamentous
      stretching. However, such treatments, which include physical therapeutic,
      chiropractic, and bracing techniques, are inconsistently supported by current
      evidence. In this study, we assess the possible benefits of asymmetrical
      strengthening of truncal muscles on the convex side of the scoliotic curve
      through a single yoga pose, the side plank pose, in idiopathic and degenerative
      scoliosis. METHODS: Twenty-five patients with idiopathic or degenerative
      scoliosis and primary curves measuring 6 to 120 degrees by the Cobb method had
      spinal radiographs and were then taught the side plank pose. After 1 week
      performing the pose with convexity downward for 10 to 20 seconds, they were
      instructed to maintain the posture once daily for as long as possible on that one
      side only. A second series of spinal radiographs was taken 3 to 22 months later.
      Pre- and post-yoga Cobb measurements were compared. RESULTS: The mean self
      reported practice of the yoga pose was 1.5 minutes per day, 6.1 days per week,
      for a mean follow-up period of 6.8 months. Among all patients, a significant
      improvement in the Cobb angle of the primary scoliotic curve of 32.0% was found.
      Among 19 compliant patients, the mean improvement rose to 40.9%. Improvements did
      not differ significantly among adolescent idiopathic and degenerative subtypes
      (49.6% and 38.4%, respectively). CONCLUSIONS: Asymmetrically strengthening the
      convex side of the primary curve with daily practice of the side plank pose held
      for as long as possible for an average of 6.8 months significantly reduced the
      angle of primary scoliotic curves. These results warrant further testing.

PMID- 25568821
TI  - Two different strategies to facilitate involvement in healthcare improvements: a
      Swedish county council initiative.
AB  - BACKGROUND: From a management point of view, there are many different approaches
      from which to choose to engage staff members in initiatives to improve
      performance. OBJECTIVE: The present study evaluated how two different types of
      improvement strategies facilitate and encourage involvement of different
      professional groups in health-care organizations. METHODS/DESIGN: Empirical data
      of two different types of strategies were collected within an improvement project
      in a County Council in Sweden. The data analysis was carried out through
      classifying the participants' profession, position, gender, and the
      organizational administration of which they were a part, in relation to their
      participation. SETTING: An improvement project in a County Council in Sweden.
      PARTICIPANTS: Designed Improvement Processes consisted of n=105 teams and
      Intrapreneurship Projects of n=202 projects. INTERVENTION: Two different types of
      improvement strategies, Designed Improvement Processes and Intrapreneurship
      Projects. MAIN OUTCOME MEASURES: How two different types of improvement
      strategies facilitate and encourage involvement of different professional groups
      in healthcare organizations. RESULTS: Nurses were the largest group participating
      in both improvement initiatives. Physicians were also well represented, although
      they seemed to prefer the less structured Intrapreneurship Projects approach.
      Assistant nurses, being the second largest staff group, were poorly represented
      in both initiatives. This indicates that the benefits and support for one group
      may push another group aside. CONCLUSIONS: Managers need to give prerequisites
      and incentives for staff who do not participate in improvements to do so.
      Comparisons of different types of improvement initiatives are an underused
      research strategy that yields interesting and thoughtful results.

PMID- 25568822
TI  - Fostering Health Creation: Community Development to Address Long-term Conditions.

PMID- 25568823
TI  - Effective Tobacco Cessation via Health Coaching: An Institutional Case Report.
AB  - BACKGROUND: Tobacco abuse is a well-recognized scourge on health and healthcare
      costs. Attempts to facilitate tobacco cessation are rarely better than marginally
      effective. PRIMARY OBJECTIVE: To describe an observational trial of an existing
      and highly successful tobacco cessation program featuring health coaching as the
      primary intervention. Core components of program design and data are presented
      and may serve as a model for other public health settings. METHODS: Health
      coaching and three complementary program components (auriculotherapy, alpha
      electrical stimulation, and relaxation techniques) are presented. Quit rates at 6
      months for 161 patients over 3 years are provided featuring 30-day point
      prevalence smoke free and intent-to-treat values. Comparisons for telephonic vs
      in-clinic health coaching, free choice vs mandated participation, and program
      costs are provided. RESULTS: Point prevalence quit rate was 88.7% while the more
      conservative intent-to-treat quit rate was 51.6%. Telephonic and in-clinic health
      coaching were not significantly different at any time point. Smoke-free rates at
      6 and 12 months were 76.9% and 63.2%, respectively. CONCLUSIONS: Two cost
      effective smoking cessation models featuring health coaching are presented. Point
      prevalence (30-day) above 80% and an enduring effect was seen. Personal and
      societal burdens (health and financial) of tobacco use might be greatly impacted
      if such programs were successfully implemented on a larger scale.

PMID- 25568824
TI  - Effects of Self-induced Unclassified Therapeutic Tremors on Quality of Life Among
      Non-professional Caregivers: A Pilot Study.
AB  - BACKGROUND: Chronic stress has a negative effect on health-related quality of
      life. In challenging environments with multiple stressors, limited access to
      mental health resources, and cultural impediments to health care delivery,
      effective and accessible methods of stress management are critical. Activation of
      self-induced therapeutic tremors (SUTT) may mitigate excess stress and improve
      quality of life (QoL) under such conditions. OBJECTIVES: To investigate (1) the
      feasibility of a 10-week SUTT training and practice intervention and (2) the
      association between participants' use of SUTT and any changes in their self
      reported health-related QoL. METHODS: All staff members of the SOS Children's
      Village in Cape Town, South Africa (n=21) received 10 weeks of SUTT weekly
      training and group practice along with independent SUTT practice 2 to 3 times
      weekly. A wellness-based QoL questionnaire was administered before and after the
      intervention, and participants were instructed to keep a diary of their
      experiences. RESULTS: Following 10 weeks of SUTT instruction and practice (1)
      there was a 91.3% adherence rate to the intervention protocol and (2)
      participants reported their overall impressions of changes in all five QoL
      domains increased at a statistically significant level: mean scores were 3.81 at
      pre-test and 4.35 at post-test (P<.05). CONCLUSIONS: A 10-week SUTT instruction
      and practice protocol is both highly feasible among non-professional caregivers
      and a potential therapeutic method for improving QoL.

PMID- 25568826
TI  - Time to reject the "one size fits all" myth.

PMID- 25568825
TI  - Integrative therapies for low back pain that include complementary and
      alternative medicine care: a systematic review.
AB  - STUDY DESIGN: Systematic review of the literature. OBJECTIVE: To evaluate whether
      an integrated approach that includes different Complementary and Alternative
      Medicine (CAM) therapies combined or CAM therapies combined with conventional
      medical care is more effective for the management of low back pain (LBP) than
      single modalities alone. SUMMARY OF BACKGROUND DATA: LBP is one of the leading
      causes of disability worldwide, yet its optimal management is still unresolved.
      METHODS: The PRISMA Statement guidelines were followed. The Cochrane Back Review
      Group scale was used to rate the quality of the studies found. RESULTS: Twenty
      one studies were found that met the inclusion criteria. The CAM modalities used
      in the studies included spinal manipulative therapy, acupuncture, exercise
      therapy, physiotherapy, massage therapy, and a topical ointment. Twenty studies
      included acupuncture and/or spinal manipulative therapy. Nine high quality
      studies showed that integrative care was clinically effective for the management
      of LBP. Spinal manipulative therapy combined with exercise therapy and
      acupuncture combined with conventional medical care or with exercise therapy
      appears to be promising approaches to the management of chronic cases of LBP.
      CONCLUSIONS: There is support in the literature for integrated CAM and
      conventional medical therapy for the management of chronic LBP. Further research
      into the integrated management of LBP is clearly needed to provide better
      guidance for patients and clinicians.

PMID- 25568827
TI  - Physician obesity: the tipping point.

PMID- 25568828
TI  - Regular consumption of sauerkraut and its effect on human health: a bibliometric
      analysis.
AB  - BACKGROUND: Sauerkraut is one of the most common and oldest forms of preserving
      cabbage and can be traced back as a food source to the 4th century BC. It
      contains a large quantity of lactic acid and tyramines, as well as vitamins and
      minerals, and has few calories. OBJECTIVE: We aimed to provide an overview
      regarding the evidence of the effects of sauerkraut on human health by means of a
      bibliometric analysis. METHODOLOGY: Electronic databases (Medline, AMED, CamBase,
      CamQuest, the Cochrane Central Register of Controlled Trials, the Database of
      Abstracts of Reviews of Effects, the Cochrane Database of Systematic Reviews,
      EMBASE, the Karger-Publisher and the Thieme-Publisher databases) were searched
      from their inception until September 2012. RESULTS: The search revealed 139
      publications ranging over a 90-year period from 1921 to 2012. The majority of
      publications originated from Europe (48.6%), followed by the United States
      (30.7%) and Asia (10%). More than half of the research (56.8%) focused on food
      analysis, and 23.7% evaluated the impact of sauerkraut on health, including risk
      factors or digestive well-being. Direct research in humans was almost constant
      over time at about 11.5%. The studies found that sauerkraut induced inflammation
      locally, but repeated intake may result in diarrhea. Some studies pointed out
      anticarcinogenic effects of sauerkraut, while others concentrated on the
      interaction with monoamine oxidase inhibitors (MAOIs). DISCUSSION: Sauerkraut,
      one of the oldest traditional foods, has a variety of beneficial effects on human
      health. However, unwanted effects such as intolerance reactions must be
      considered when dealing with sauerkraut as a functional food.

PMID- 25568830
TI  - The Impact of a Food Elimination Diet on Collegiate Athletes' 300-meter Run Time
      and Concentration.
AB  - BACKGROUND: Optimal human function and performance through diet strategies are
      critical for everyone but especially for those involved in collegiate or
      professional athletics. Currently, individualized medicine (IM) is emerging as a
      more efficacious approach to health with emphasis on personalized diet strategies
      for the public and is common practice for elite athletes. One method for
      directing patient-specific foods in the diet, while concomitantly impacting
      physical performance, may be via IgG food sensitivity and Candida albicans
      analysis from dried blood spot (DBS) collections. METHODS: The authors designed a
      quasi-experimental, nonrandomized, pilot study without a control group. Twenty
      three participants, 15 female, 8 male, from soccer/volleyball and football
      athletic teams, respectively, mean age 19.64+0.86 years, were recruited for the
      study, which examined preposttest 300-meter run times and questionnaire responses
      after a 14-day IgG DBS-directed food elimination diet based on IgG reactivity to
      93 foods. DBS specimen collection, 300-meter run times, and Learning Difficulties
      Assessment (LDA) questionnaires were collected at the participants' university
      athletics building on campus. IgG, C albicans, and S cerevisiae analyses were
      conducted at the Great Plains Laboratory, Lenexa, Kansas. RESULTS: Data indicated
      a change in 300-meter run time but not of statistical significance (run time
      baseline mean=50.41 sec, run time intervention mean=50.14 sec). Descriptive
      statistics for frequency of responses and chi-square analysis revealed that 4 of
      the 23 items selected from the LDA (Listening-Memory and Concentration subscale
      R=.8669; Listening-Information Processing subscale R=.8517; and General
      Concentration and Memory subscale R=.9019) were improved posttest. CONCLUSION:
      The study results did not indicate merit in eliminating foods based on IgG
      reactivity for affecting athletic performance (faster 300-meter run time) but did
      reveal potential for affecting academic qualities of listening, information
      processing, concentration, and memory. Further studies are warranted evaluating
      IgG-directed food elimination diets for improving run time, concentration, and
      memory among college athletes as well as among other populations.

PMID- 25568829
TI  - Survey to determine why people drink raw milk.
AB  - BACKGROUND: Fragility fractures associated with osteoporosis extract a large
      financial and personal toll on society. Pharmaceutical or dietary calcium intake
      is needed to increase bone mineral density to prevent fragility fractures.
      Although dairy products are a good source of calcium, patients who are unable to
      digest lactose tend to avoid them and are put at a greater risk for fracture than
      the general population. Anecdotal reports suggest that lactose maldigesters, when
      consuming raw milk, have a dramatic reduction in symptoms relative to pasteurized
      milk. The mechanism of the reported reduction in symptoms, if true, is unknown.
      The purpose of the current study was to survey raw milk drinkers to ascertain
      their health-related motivations for consuming raw milk, especially as they
      relate to lactose maldigestion. METHODS: An online survey regarding raw milk was
      completed by 153 of 1527 members of a raw milk-buying community. RESULTS: The
      primary reason the respondents cited for drinking raw milk was that they believed
      it was more healthful; 30% reported some gastrointestinal discomfort when
      drinking pasteurized milk, yet almost all (99%) reported consuming raw milk
      without discomfort. Despite the reports of gastrointestinal discomfort, only 5%
      of respondents had been diagnosed as lactose intolerant by a medical
      professional, and only 1% had been diagnosed as lactose intolerant via the gold
      standard hydrogen breath test. CONCLUSIONS: The primary motivation for drinking
      raw milk is its perceived health value, not its digestibility. Although raw milk
      appears to be more easily digested than pasteurized milk in our survey sample,
      the mechanism of digestibility remains unknown.

PMID- 25568831
TI  - Innovation in diabetes care: improving consumption of healthy food through a
      "chef coaching" program: a case report.
AB  - Nutrition therapy as part of lifestyle care is recommended for people with type 2
      diabetes. However, most people with diabetes do not follow this guideline.
      Changing eating habits involves obtaining knowledge and building practical skills
      such as shopping, meal preparation, and food storage. Just as fitness coaches use
      their specific knowledge base in fitness to enhance the effectiveness of their
      coaching, credentialed chefs trained as health coaches might combine their
      culinary expertise with coaching in order to improve clients' food choices and
      lifestyles. This report documents the case of a 55-year-old white male physician,
      single and living alone, who was recently diagnosed with type 2 diabetes and
      reported chronic stress, sedentary behavior, and unhealthy eating habits. He
      participated in a chef coaching program of 8 weekly one-on-one 30-minute coaching
      sessions via Skype delivered by a chef trained as a health coach. During the
      first five meetings, the patient's goals were primarily culinary; however, with
      his success in accomplishing these goals, the patient progressed and expanded his
      goals to include other lifestyle domains, specifically exercise and work-life
      balance. At the end of the program, the patient had improved both his nutritional
      and exercise habits, his confidence in further self-care improvement, and his
      health parameters such as HgA1c (8.8% to 6.7%; normal <6.5%). We conclude that
      chef coaching has the potential to help people with diabetes improve their
      practical culinary skills and implement them so that they eat better and,
      further, has the potential to help them improve their overall self-care. We
      intend to further develop chef coaching and assess its potential as we learn from
      its implementation. 

PMID- 25568832
TI  - Customized nutritional enhancement for pregnant women appears to lower incidence
      of certain common maternal and neonatal complications: an observational study.
AB  - A retrospective chart review analyzed the effect of customized nutrition on the
      incidence of pregnancy-induced hypertension (PIH), gestational diabetes (GDM),
      and small- and large-for-gestational-age (SGA, LGA) neonates, examining
      consecutive deliveries between January 1, 2011, and Decem ber 31, 2012, at a low
      risk community hospital. The population was divided into 3 groups: (1) study
      group (SG), (2) private practice (PP), and (3) community healthcare clinic
      (CHCC). All groups received standard perinatal management, but additionally the
      study group was analyzed for serum zinc, carnitine, total 25-hydroxy
      cholecalciferol (25 OH-D), methylene tetrahydrofolate reductase, and catechol-O
      methyl transferase polymorphisms in the first trimester prior to intervention,
      with subsequent second trimester and postpartum assessment of zinc, carnitine,
      and 25 OH-D after intervention. Intervention consisted of trimesterby-trimester
      nutrition and lifestyle education, supplementation of L-methyl folate, magnesium,
      essential fatty acids, and probiotics for all SG patients, with targeted
      supplementation of zinc, carnitine, and 25 OH-D. Because of small case occurrence
      rates of individual conditions in the study group, unreportable reductions were
      found, except GDM (SG vs CHCC, P value .046 with 95.38% confidence interval
      [CI]), and PIH (SG vs PP, P value .0505 with 94.95% CIl). The aggregated
      occurrence rate of the four conditions, however, was significantly lower in the
      study population than in either comparison population (PP P value .0154 with
      98.46% CI, and CHCC P value .0265 with 97.35% CI). Customized nutritional
      intervention appears to have significantly reduced adverse perinatal outcomes.
      Prospective study within larger, at-risk populations is needed to determine
      whether customized nutrition improves conditions individually. 

PMID- 25568833
TI  - Introduction: What to Eat When You Can't Eat.

PMID- 25568835
TI  - Classifying Imbalanced Data Streams via Dynamic Feature Group Weighting with
      Importance Sampling.
AB  - Data stream classification and imbalanced data learning are two important areas
      of data mining research. Each has been well studied to date with many interesting
      algorithms developed. However, only a few approaches reported in literature
      address the intersection of these two fields due to their complex interplay. In
      this work, we proposed an importance sampling driven, dynamic feature group
      weighting framework (DFGW-IS) for classifying data streams of imbalanced
      distribution. Two components are tightly incorporated into the proposed approach
      to address the intrinsic characteristics of concept-drifting, imbalanced
      streaming data. Specifically, the ever-evolving concepts are tackled by a
      weighted ensemble trained on a set of feature groups with each sub-classifier
      (i.e. a single classifier or an ensemble) weighed by its discriminative power and
      stable level. The un-even class distribution, on the other hand, is typically
      battled by the sub-classifier built in a specific feature group with the
      underlying distribution rebalanced by the importance sampling technique. We
      derived the theoretical upper bound for the generalization error of the proposed
      algorithm. We also studied the empirical performance of our method on a set of
      benchmark synthetic and real world data, and significant improvement has been
      achieved over the competing algorithms in terms of standard evaluation metrics
      and parallel running time. Algorithm implementations and datasets are available
      upon request.

PMID- 25568834
TI  - Comparison of intravital thinned skull and cranial window approaches to study CNS
      immunobiology in the mouse cortex.
AB  - Fluorescent imaging coupled with high-resolution femto-second pulsed infrared
      lasers allows for interrogation of cellular interactions deeper in living tissues
      than ever imagined. Intra-vital imaging of the central nervous system (CNS) has
      provided insights into neuronal development, synaptic transmission, and even
      immune interactions. In this review we will discuss the two most common
      intravital approaches for studying the cerebral cortex in the live mouse brain
      for pre-clinical studies, the thinned skull and cranial window techniques, and
      focus on the advantages and drawbacks of each approach. In addition, we will
      discuss the use of neuronal physiologic parameters as determinants of successful
      surgical and imaging preparation.

PMID- 25568836
TI  - Genetic evidence for a pathogenic role for the vitamin D3 metabolizing enzyme
      CYP24A1 in multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a common disease of the central nervous
      system and a major cause of disability amongst young adults. Genome-wide
      association studies have identified many novel susceptibility loci including
      rs2248359. We hypothesized that genotypes of this locus could increase the risk
      of MS by regulating expression of neighboring gene, CYP24A1 which encodes the
      enzyme responsible for initiating degradation of 1,25-dihydroxyvitamin D3.
      METHODS: We investigated this hypothesis using paired gene expression and
      genotyping data from three independent datasets of neurologically healthy adults
      of European descent. The UK Brain Expression Consortium (UKBEC) consists of post
      mortem samples across 10 brain regions originating from 134 individuals (1231
      samples total). The North American Brain Expression Consortium (NABEC) consists
      of cerebellum and frontal cortex samples from 304 individuals (605 samples
      total). The brain dataset from Heinzen and colleagues consists of prefrontal
      cortex samples from 93 individuals. Additionally, we used gene network analysis
      to analyze UKBEC expression data to understand CYP24A1 function in human brain.
      FINDINGS: The risk allele, rs2248359-C, is strongly associated with increased
      expression of CYP24A1 in frontal cortex (p-value=1.45*10-13), but not white
      matter. This association was replicated using data from NABEC (p-value=7.2*10-6)
      and Heinzen and colleagues (p-value=1.2*10-4). Network analysis shows a
      significant enrichment of terms related to immune response in eight out of the 10
      brain regions. INTERPRETATION: The known MS risk allele rs2248359-C increases
      CYP24A1 expression in human brain providing a genetic link between MS and vitamin
      D metabolism, and predicting that the physiologically active form of vitamin D3
      is protective. Vitamin D3's involvement in MS may relate to its immunomodulatory
      functions in human brain. FUNDING: Medical Research Council UK; King Faisal
      Specialist Hospital and Research Centre, Saudi Arabia; Intramural Research
      Program of the National Institute on Aging, National Institutes of Health, USA.

PMID- 25568837
TI  - Survey of current enteral nutrition practices in treatment of amyotrophic lateral
      sclerosis.
AB  - BACKGROUND AND AIMS: Enteral nutrition (EN) is commonly prescribed for dysphagia
      and weight loss in amyotrophic lateral sclerosis (ALS), but there are currently
      no ALS-specific EN guidelines. We aimed to survey current practices prescribing
      EN to ALS patients. METHODS: An online survey was distributed using list servers
      administered by the Academy of Nutrition and Dietetics (AND), Muscular Dystrophy
      Association (MDA), and ALS Association (ALSA). RESULTS: A total of 148
      dietitians, nurses, and physicians participated in the survey, of whom 50% were
      dietitians and 68% were associated with an ALS clinic. Only 47% of respondents
      reported their patients to be fully compliant with EN recommendations. Side
      effects (fullness, diarrhea, constipation, and bloating) were the most important
      reason for patient noncompliance, followed by dependence on caregivers. By
      contrast, only 3% of providers rated depression/hopelessness as the most
      important reason for noncompliance. Half of those surveyed reported that more
      than 25% of patients continued to lose weight after starting EN. CONCLUSIONS: Our
      survey results show a high frequency of gastrointestinal side effects and weight
      loss in ALS patients receiving EN. These findings may be limited by sampling
      error and non-response bias. Prospective studies are needed to help establish EN
      guidelines for ALS.

PMID- 25568838
TI  - The role of bicycle sharing systems in normalising the image of cycling: An
      observational study of London cyclists.
AB  - Bicycle sharing systems are increasingly popular around the world and have the
      potential to increase the visibility of people cycling in everyday clothing. This
      may in turn help normalise the image of cycling, and reduce perceptions that
      cycling is 'risky' or 'only for sporty people'. This paper sought to compare the
      use of specialist cycling clothing between users of the London bicycle sharing
      system (LBSS) and cyclists using personal bicycles. To do this, we observed 3594
      people on bicycles at 35 randomly-selected locations across central and inner
      London. The 592 LBSS users were much less likely to wear helmets (16% vs. 64%
      among personal-bicycle cyclists), high-visibility clothes (11% vs. 35%) and
      sports clothes (2% vs. 25%). In total, 79% of LBSS users wore none of these types
      of specialist cycling clothing, as compared to only 30% of personal-bicycle
      cyclists. This was true of male and female LBSS cyclists alike (all p>0.25 for
      interaction). We conclude that bicycle sharing systems may not only encourage
      cycling directly, by providing bicycles to rent, but also indirectly, by
      increasing the number and diversity of cycling 'role models' visible.

PMID- 25568839
TI  - Independent mobility on the journey to school: A joint cross-sectional and
      prospective exploration of social and physical environmental influences.
AB  - BACKGROUND: Despite related physical/mental health benefits, children's
      independent mobility for school travel (i.e. walking/cycling without adult
      accompaniment) has declined in recent decades. PURPOSE: To examine cross
      sectional and longitudinal associations between social/physical environmental
      variables and independent mobility on the school journey. METHODS: Participants
      were 1121 9-10 year-olds residing within 1600 m of their school in urban/rural
      areas of Norfolk, UK in 2007 (T1). At one year (T2) 491 children were followed
      up. At T1, parents survey-reported perceptions of the social/physical environment
      and rules regarding their child's physical activity. Characteristics of the
      neighborhood, route to school and school environment were measured using a
      Geographical Information System and school audits. At both time-points children
      survey-reported their usual travel mode and whether accompanied. Regression
      analyses were conducted in 2013. RESULTS: Around half walked/cycled to school
      without adult accompaniment (T1, 43%; T2, 53%). Parents often allowing their
      child to play outside anywhere within the neighborhood (adjusted odds ratio (AOR)
      3.14 (95% CI 1.24-7.96)) and household car access (AOR 0.27 (95% CI 0.08-0.94))
      were associated longitudinally with boys walking/cycling independently to school.
      Land use mix (AOR 1.38 (95% CI 1.06-1.79)), proportion of main roads in the
      neighborhood (AOR 0.67 (95% CI 0.47-0.94)) and parental encouragement for
      walking/cycling (AOR 0.40 (95% CI 0.20-0.80)) were associated longitudinally with
      girls walking/cycling independently to school. CONCLUSIONS: Interventions should
      develop parents' skills to teach their children to be independently mobile and to
      build confidence regarding venturing out without parental accompaniment. Urban
      planners should consider designing neighborhoods in which residences,
      business/retail outlets and sports facilities are co-located to promote active
      transport.

PMID- 25568840
TI  - A biographical approach to studying individual change and continuity in walking
      and cycling over the life course.
AB  - Most research studies seeking to understand walking and cycling behaviours have
      used cross-sectional data to explain inter-individual differences at a particular
      point in time. Investigations of individual walking and cycling over time are
      limited, despite the fact that insights on this could be valuable for informing
      policies to support life-long walking and cycling. The lack of existing
      longitudinal data, difficulties associated with its collection and scepticism
      towards retrospective methods as a means to reconstruct past behavioural
      developments have all contributed to this deficit in knowledge. This issue is
      heightened when the time frame extends to longer term periods, or the life course
      in its entirety. This paper proposes and details a retrospective qualitative
      methodology that was used to study individual change and stability in walking and
      cycling within a life course framework. Biographical interviews supported by a
      life history calendar were developed and conducted with two adult birth cohorts.
      Interpretive, visual biographies were produced from the interview materials.
      Analysis focused on identifying the occurrence, context and timing of behavioural
      change and stability over the life course. Typologies of behavioural development
      were generated to resolve common and distinct behavioural patterns over the life
      course. Whilst the validity of reconstructed biographies of walking and cycling
      cannot be proven, this is an approach which offers credible and confirmable
      insights on how these behaviours increase, diminish, persist, cease, are restored
      or adapted through the life course, and how behavioural trajectories of walking
      and cycling may be evolving through historical time.

PMID- 25568841
TI  - HDL-Associated Paraoxonase 1 as a Bridge between Postmenopausal Osteoporosis and
      Cardiovascular Disease.
AB  - The association of postmenopausal osteoporosis (PMOP) with both atherosclerosis
      and vascular/valvular calcification is well known. Recently, ample evidence has
      suggested a common etiologic factor, namely, reduced HDL-associated paraoxonase 1
      (PON1) activity, as a causative factor in the development of PMOP and
      cardiovascular disease (CVD). This common etiologic factor not only contributes
      to atherosclerotic diseases but also to PMOP following an almost identical
      mechanism including dysfunctional HDL and lipid oxidation. According to recent
      studies, lipid oxidation might improve osteoblastic transformation of vascular
      cells and obstruct such transformation in bone cells. The primary objective of
      this current review was to summarize the evidence revealing the role of HDL
      associated PON1 enzyme in PMOP. Additionally, the review aimed to address some of
      the subjects that need further investigation in order to define whether
      hyperhomocysteinemia and sensitivity to lipid oxidation may be risk factors for
      PMOP. 

PMID- 25568842
TI  - Use of umbilical cord serum in ophthalmology.
AB  - Among blood preparations, serum has been topically used in the management of
      various ocular diseases in ophthalmology. Like peripheral blood serum, umbilical
      cord blood serum contains a high concentration of essential tear components,
      growth factors, neurotrophic factors, vitamin A, fibronectin, prealbumin, and
      oil. Umbilical cord serum can provide basic nutrients for epithelial renewal and
      can facilitate the proliferation, migration, and differentiation of the ocular
      surface epithelium. Eye drops made from umbilical cord serum have been applied to
      treat various ocular surface diseases, including severe dry eye with or without
      Sjogren's syndrome, ocular complications in graft-versus-host disease, persistent
      epithelial defects, neurotrophic keratopathy, recurrent corneal erosions, ocular
      chemical burn, and surface problems after corneal refractive surgery. Because
      mesenchymal stem cells from umbilical cord blood can be used to regenerate
      corneal tissue and retinal nerve cells, umbilical cord serum might be applied for
      tissue engineering and regenerative medicine in the future. 

PMID- 25568843
TI  - Effect of Propofol on microRNA Expression Profile in Adipocyte-Derived Adult Stem
      Cells.
AB  - MicroRNA (miRNA) pathways have been implicated in stem cell regulation. This
      study investigated the molecular effects of propofol on adipocyte stem cells
      (ASCs) by analyzing RNA expression arrays. Human ASCs were isolated by use of a
      liposuction procedure. ASCs were treated with saline, 50 uM propofol, or 100 uM
      propofol in culture media for 3 hours. After the isolation of total RNA, the
      expression of 76 miRNAs was evaluated with peptide nucleic acid-miRNA array
      analysis through denaturation and hybridization processes. Treatment with 50 uM
      propofol resulted in significant down-regulation of expression of 18 miRNAs and
      upregulation of expression of 25 miRNAs; 100 uM propofol resulted in significant
      downregulation of expression of 14 miRNAs and upregulation of expression of 29
      miRNAs. The lowest expression was seen for miR-204, which was 0.07-fold with 50
      uM propofol and 0.18-fold with 100 uM propofol. The highest expression was seen
      for miR-208b, which was 11.23-fold with 50 uM propofol and 11.20-fold with 100 uM
      propofol. Expression patterns of miRNAs were not significantly different between
      50 uM and 100 uM propofol treatment. The results of this study suggest that
      propofol is involved in altering the miRNA expression level in human ASCs.
      Additional research is necessary to establish the functional effect of miRNA
      alteration by propofol. 

PMID- 25568844
TI  - Intraoperative Observation of the Degree and Pattern of Urine Leakage before
      Adjustment of the Mesh during a Transobturator Tape Procedure.
AB  - Most intraoperative provocative tests previously reported were performed after
      mesh adjustment to confirm the absence of urine leakage. Instead, our test was
      performed before adjustment of the mesh to control the tape tension after
      observing the pattern of the urine leakage. We studied whether this method had an
      effect on the success rate of transobturator tape (TOT) procedures. A total of 96
      patients were included: 47 patients underwent TOT procedures without
      intraoperative testing (Group I) and 49 patients underwent TOT procedures with
      testing (Group II). Bladder filling was performed with at least 300 ml of normal
      saline during the test. After observing the pattern of the urine leakage before
      adjustment of the mesh by coughing or manual pressure on the suprapubic area, we
      controlled the mesh tension. In Group I, which did not undergo the intraoperative
      test, the Valsalva leak-point pressure, cough leak-point pressure, preoperative
      and postoperative peak flow velocity (Qmax), and postvoiding residual urine (PVR)
      were 86.46 cmH2O, 101.91 cmH2O, 20.82 ml/s, 22.74 ml/s, 19.77 ml, and 45.98 ml,
      respectively. Changes in the postoperative and preoperative Qmax and PVR were
      1.92 ml/s and 26.21 ml, respectively. In Group II, in which the test was applied,
      the corresponding results were 85.50 cmH2O, 100.45 cmH2O, 25.60 ml/s, 26.90 ml/s,
      17.16 ml, and 29.67 ml, respectively. Changes in the postoperative and
      preoperative Qmax and PVR were 1.3 ml/s and 12.51 ml, respectively. The two
      groups showed no significant differences in any of the variables. In Group I, the
      cure and improvement rates were 70.2% and 27.7%, respectively. In Group II, the
      rates were 91.8% and 8.2%, respectively. Group II had a significantly higher
      success rate than Group I (p value= 0.011). In the univariable logistic
      regression analysis, Group II exhibited a higher odds ratio (4.771) than Group I
      in terms of cure rate, and Group II had a higher success rate than Group I (p
      value=0.011). In the multivariable logistic regression analysis, Group II
      exhibited a higher odds ratio (4.700) than Group I in terms of cure rate under
      calculation of the variables (namely, age, hypertension, preoperative Qmax, and
      PVR), and the cure rate of Group II was verified to be significantly higher than
      that of Group I (p value=0.019). We suggest that our test is an effective method
      to confirm whether adequate tension is being applied to the tape. Our method
      presents some advantages in that surgeons can control and adjust the tension of
      the mesh after observing the degree and pattern of the urine leakage. 

PMID- 25568845
TI  - Risk factors for distant metastasis as a primary site of treatment failure in
      early-stage breast cancer.
AB  - The aim of this study was to evaluate the risk factors for distant metastasis
      (DM) as a primary site of failure in early-stage breast cancer. Data from 294
      patients diagnosed with pathologic stage I or II breast cancer between January
      2000 and December 2005 were reviewed retrospectively. Median follow-up duration
      was 81.0 months (range, 18-135 months). The total number of patients with DM
      without evidence of locoregional recurrence was 20 and the median time between
      surgery and DM was 29 months (range, 9-79 months). Median survival time was 38
      months (range, 22-77 months) after operation. HER-2 positivity (p=0.015), T stage
      of tumor (p=0.012), and number of involved lymph nodes (p=0.008) were significant
      predictors of DM in the univariable analysis. Number of involved lymph nodes
      [p=0.005, hazards ratio (HR): 1.741; 95% confidence interval (CI): 1.178-2.574]
      and HER-2 positivity (p=0.018, HR: 2.888; 95% CI: 1.201-6.941) had a
      statistically significant effect on DM-free survival in the multivariable
      analysis. A cautious evaluation may be helpful when patients with risk factors
      for DM have symptoms implying the possibility of DM. To reduce DM, applying
      intensive therapy is needed after curative surgery for patients with high risk
      for DM. 

PMID- 25568846
TI  - OCT-1, ABCB1, and ABCG2 Expression in Imatinib-Resistant Chronic Myeloid Leukemia
      Treated with Dasatinib or Nilotinib.
AB  - This study explored drug transporter expression levels and their impact on
      clinical response to imatinib and second-generation tyrosine kinase inhibitors
      (TKIs) in imatinib- resistant chronic myeloid leukemia (CML). Imatinib-resistant
      chronic phase CML patients treated with dasatinib (n=10) and nilotinib (n=12)
      were enrolled. The mRNA expression of the OCT-1, ABCG2, and ABCB1 genes was
      quantified by using paired bone marrow samples obtained before administering
      imatinib and at the point of detecting imatinib resistance (just before starting
      second-generation TKIs). The expression levels of OCT-1 and ABCG2 were lower in
      follow-up than in imatinib-naive samples. ABCB1 revealed highly variable
      expression levels before and after imatinib treatment. In addition, median ABCB1
      expression in follow-up samples was lower in patients achieving complete
      cytogenetic response or major molecular response during imatinib treatment than
      in failed patients. Higher ABCG2 expression in imatinib-exposed samples showed a
      negative impact on optimal response to dasatinib. Patients with higher ABCG2
      expression in imatinib-exposed samples also had shorter progression- free
      survival with dasatinib treatment. However, no significant correlation was found
      between these drug transporter expression levels in imatinib-naive or imatinib-
      exposed samples and responses to nilotinib. In imatinib-resistant CML, OCT-1 and
      ABCG2 mRNA expression decreased after imatinib treatment. Patients with higher
      ABCG2 expression in imatinib-exposed samples showed poor treatment outcome with
      dasatinib. On the other hand, a higher expression level of ABCB1 in imatinib
      exposed samples did not affect second-generation TKI responses but was correlated
      with poor imatinib responses. 

PMID- 25568847
TI  - Thrombotic Occlusion during Intravascular Ultrasonography-Guided Percutaneous
      Coronary Intervention of Stumpless Chronic Total Occlusion.
AB  - Percutaneous coronary intervention (PCI) of stumpless chronic total occlusion
      (CTO) lesions with a side branch stemming from the occlusion have a significantly
      lower treatment success rate because physicians cannot identify an accurate entry
      point with only conventional angiographic images. An intravascular
      ultrasonography (IVUS)-guided wiring technique might be useful for the
      penetration of stumpless CTO. We recently experienced thrombotic occlusion during
      an IVUS-guided stumpless CTO procedure. The cause of the thrombosis is not
      completely understood; the thrombosis may have been associated with the long use
      of the IVUS catheter. Special precautions should be taken to prevent thrombus in
      such cases. 

PMID- 25568848
TI  - Recurrent pneumothorax after etanercept therapy in a rheumatoid arthritis
      patient: a case report.
AB  - The use of anti-tumor necrosis factor (anti-TNF) agents for rheumatoid arthritis
      (RA) patients who are refractory to disease-modifying anti-rheumatic drugs is
      gradually increasing. Etanercept is the first anti-TNF agent to be approved for
      RA treatment and is also the most widely used. However, aggravation of
      interstitial lung disease after etanercept treatment in RA patients has been
      reported recently. We report the first case of recurrent spontaneous pneumothorax
      with progression of interstitial lung disease after initiating etanercept
      therapy. The withdrawal of etanercept and a change to adalimumab, a different
      class of TNF inhibitor, achieved clinical stabilization. 

PMID- 25568849
TI  - Insufficiency fracture after radiation therapy.
AB  - Insufficiency fracture occurs when normal or physiological stress applied to
      weakened bone with demineralization and decreased elastic resistance. Recently,
      many studies reported the development of IF after radiation therapy (RT) in
      gynecological cancer, prostate cancer, anal cancer and rectal cancer. The RT
      induced insufficiency fracture is a common complication during the follow-up
      using modern imaging studies. The clinical suspicion and knowledge the
      characteristic imaging patterns of insufficiency fracture is essential to
      differentiate it from metastatic bone lesions, because it sometimes cause severe
      pain, and it may be confused with bone metastasis. 

PMID- 25568850
TI  - Vertebral compression fractures after spine irradiation using conventional
      fractionation in patients with metastatic colorectal cancer.
AB  - PURPOSE: To evaluate the risk of vertebral compression fracture (VCF) after
      conventional radiotherapy (RT) for colorectal cancer (CRC) with spine metastasis
      and to identify risk factors for VCF in metastatic and non-metastatic irradiated
      spines. MATERIALS AND METHODS: We retrospectively reviewed 68 spinal segments in
      16 patients who received conventional RT between 2009 and 2012. Fracture was
      defined as a newly developed VCF or progression of an existing fracture. The
      target volume included all metastatic spinal segments and one additional non
      metastatic vertebra adjacent to the tumor-involved spines. RESULTS: The median
      follow-up was 7.8 months. Among all 68 spinal segments, there were six fracture
      events (8.8%) including three new VCFs and three fracture progressions. Observed
      VCF rates in vertebral segments with prior irradiation or pre-existing
      compression fracture were 30.0% and 75.0% respectively, compared with 5.2% and
      4.7% for segments without prior irradiation or pre-existing compression fracture,
      respectively (both p < 0.05). The 1-year fracture-free probability was 87.8% (95%
      CI, 78.2-97.4). On multivariate analysis, prior irradiation (HR, 7.30; 95% CI,
      1.31-40.86) and pre-existing compression fracture (HR, 18.45; 95% CI, 3.42-99.52)
      were independent risk factors for VCF. CONCLUSION: The incidence of VCF following
      conventional RT to the spine is not particularly high, regardless of metastatic
      tumor involvement. Spines that received irradiation and/or have pre-existing
      compression fracture before RT have an increased risk of VCF and require close
      observation.

PMID- 25568851
TI  - Prediction of response by FDG PET early during concurrent chemoradiotherapy for
      locally advanced non-small cell lung cancer.
AB  - PURPOSE: To evaluate the predictive value of the early response of (18)F
      flurodeoxyglucose positron emission tomography (FDG PET) during concurrent
      chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC).
      MATERIALS AND METHODS: FDG PET was performed before and during CCRT for 13 NSCLC
      patients. Maximum standardized uptake value (SUVmax), mean standardized uptake
      value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)
      were measured and the changes were calculated. These early metabolic changes were
      compared with the standard tumor response by computed tomograms (CT) one month
      after CCRT. RESULTS: One month after the completion of CCRT, 9 patients had
      partial response (PR) of tumor and 4 patients had stable disease. The percent
      changes of SUVmax (%DeltaSUVmax) were larger in responder group than in non
      responder group (55.7% +/- 15.6% vs. 23.1% +/- 19.0%, p = 0.01). The percent
      changes of SUVmean (%DeltaSUVmean) were also larger in responder group than in
      non-responder group (54.4% +/- 15.9% vs. 22.3% +/- 23.0%, p = 0.01). The percent
      changes of MTV (%DeltaMTV) or TLG (%DeltaTLG) had no correlation with the tumor
      response after treatment. All the 7 patients (100%) with %DeltaSUVmax >= 50% had
      PR, but only 2 out of 6 patients (33%) with %DeltaSUVmax < 50% had PR after CCRT
      (p = 0.009). Likewise, all the 6 patients (100%) with %DeltaSUVmean >= 50% had
      PR, but only 3 out of 7 patients (43%) with %DeltaSUVmean < 50% had PR after CCRT
      (p = 0.026). CONCLUSION: The degree of metabolic changes measured by PET-CT
      during CCRT was predictive for NSCLC tumor response after CCRT.

PMID- 25568852
TI  - Clinical outcome of high-dose-rate interstitial brachytherapy in patients with
      oral cavity cancer.
AB  - PURPOSE: To evaluate the clinical outcome of high-dose-rate (HDR) interstitial
      brachytherapy (IBT) in patients with oral cavity cancer. MATERIALS AND METHODS:
      Sixteen patients with oral cavity cancer treated with HDR remote-control
      afterloading brachytherapy using (192)Ir between 2001 and 2013 were analyzed
      retrospectively. Brachytherapy was administered in 11 patients as the primary
      treatment and in five patients as salvage treatment for recurrence after the
      initial surgery. In 12 patients, external beam radiotherapy (50-55 Gy/25
      fractions) was combined with IBT of 21 Gy/7 fractions. In addition, IBT was
      administered as the sole treatment in three patients with a total dose of 50
      Gy/10 fractions and as postoperative adjuvant treatment in one patient with a
      total of 35 Gy/7 fractions. RESULTS: The 5-year overall survival of the entire
      group was 70%. The actuarial local control rate after 3 years was 84%. All five
      recurrent cases after initial surgery were successfully salvaged using IBT +/-
      external beam radiotherapy. Two patients developed local recurrence at 3 and 5
      months, respectively, after IBT. The acute complications were acceptable (<=grade
      2). Three patients developed major late complications, such as radio
      osteonecrosis, in which one patient was treated by conservative therapy and two
      required surgical intervention. CONCLUSION: HDR IBT for oral cavity cancer was
      effective and acceptable in diverse clinical settings, such as in the cases of
      primary or salvage treatment.

PMID- 25568853
TI  - Is neoadjuvant androgen deprivation therapy beneficial in prostate cancer treated
      with definitive radiotherapy?
AB  - PURPOSE: To determine whether neoadjuvant androgen deprivation therapy (NADT)
      improves clinical outcomes in patients with prostate cancer treated with
      definitive radiotherapy. MATERIALS AND METHODS: We retrospectively reviewed
      medical records of 201 patients with prostate cancer treated with radiotherapy
      between January 1991 and December 2008. Of these, 156 patients with more than 3
      years of follow-up were the subjects of this study. The median duration of follow
      up was 91.2 months. NADT was given in 103 patients (66%) with median duration of
      3.3 months (range, 1.0 to 7.7 months). Radiation dose was escalated gradually
      from 64 Gy to 81 Gy using intensity-modulated radiotherapy technique. RESULTS:
      Biochemical relapse-free survival (BCRFS) and overall survival (OS) of all
      patients were 72.6% and 90.7% at 5 years, respectively. BCRFS and OS of NADT
      group were 79.5% and 89.8% at 5 years and those of radiotherapy alone group were
      58.8% and 92.3% at 5 years, respectively. Risk group (p = 0.010) and radiation
      dose >=70 Gy (p = 0.017) affected BCRFS independently. NADT was a significant
      prognostic factor in univariate analysis, but not in multivariate analysis (p =
      0.073). Radiation dose >=70 Gy was only an independent factor for OS (p = 0.007;
      hazard ratio, 0.261; 95% confidence interval, 0.071-0.963). CONCLUSION: NADT
      prior to definitive radiotherapy did not result in significant benefit in terms
      of BCRFS and OS. NADT should not be performed routinely in the era of dose
      escalated radiotherapy.

PMID- 25568855
TI  - Radiation recall dermatitis induced by tamoxifen during adjuvant breast cancer
      treatment.
AB  - Tamoxifen and radiotherapy are used in breast cancer treatment worldwide.
      Radiation recall dermatitis (RRD), induced by tamoxifen, has been rarely
      reported. Herein, we report a RRD case induced by tamoxifen. A 47-year-old woman
      had a right quadrantectomy and an axillary lymph node dissection due to breast
      cancer. The tumor was staged pT2N0; it was hormone receptor positive, and human
      epidermal growth factor receptor 2 negative. The patient received adjuvant
      chemotherapy followed by tamoxifen and radiotherapy. After 22 months of
      tamoxifen, the patient developed a localized heating sensation, tenderness,
      edema, and redness at the irradiated area of the right breast. The symptoms
      improved within 1 week without treatment. Three weeks later, however, the patient
      developed similar symptoms in the same area of the breast. She continued
      tamoxifen before and during dermatitis, and symptoms resolved within 1 week. 

PMID- 25568854
TI  - In vivo verification of regional hyperthermia in the liver.
AB  - PURPOSE: We performed invasive thermometry to verify the elevation of local
      temperature in the liver during hyperthermia. MATERIALS AND METHODS: Three 40-kg
      pigs were used for the experiments. Under general anesthesia with ultrasonography
      guidance, two glass fiber-optic sensors were placed in the liver, and one was
      placed in the peritoneal cavity in front of the liver. Another sensor was placed
      on the skin surface to assess superficial cooling. Six sessions of hyperthermia
      were delivered using the Celsius TCS electro-hyperthermia system. The energy
      delivered was increased from 240 kJ to 507 kJ during the 60-minute sessions. The
      inter-session cooling periods were at least 30 minutes. The temperature was
      recorded every 5 minutes by the four sensors during hyperthermia, and the
      increased temperatures recorded during the consecutive sessions were analyzed.
      RESULTS: As the animals were anesthetized, the baseline temperature at the start
      of each session decreased by 1.3C to 2.8C (median, 2.1C). The mean increases in
      temperature measured by the intrahepatic sensors were 2.42C (95% confidence
      interval [CI], 1.70-3.13) and 2.67C (95% CI, 2.05-3.28) during the fifth and
      sixth sessions, respectively. The corresponding values for the intraperitoneal
      sensor were 2.10C (95% CI, 0.71-3.49) and 2.87C (1.13-4.43), respectively.
      Conversely, the skin temperature was not increased but rather decreased according
      to application of the cooling system. CONCLUSION: We observed mean 2.67C and
      2.87C increases in temperature at the liver and peritoneal cavity, respectively,
      during hyperthermia. In vivo real-time thermometry is useful for directly
      measuring internal temperature during hyperthermia.

PMID- 25568857
TI  - Liver immunology: new perspectives.

PMID- 25568856
TI  - An 87-year-old patient with repeated oligorecurrences over six years whose
      disease were treated with radiotherapy alone.
AB  - In the clinical state of oligometastases or oligorecurrence, a transitional state
      between localized and widespread systemic disease, local control of the disease
      may yield improved systemic control. Radiotherapy may be a good means for
      controlling oligometastatic tumors, particularly in very old patients for whom
      surgery may be infeasible. A combination of systemic therapy and local therapy is
      necessary to prevent systemic progression. Some kinds of cancers found in the
      elderly are known to be somewhat indolent for systemic progression. So, for very
      old patients who refuse or cannot tolerate chemotherapy, the use of radical
      radiotherapy alone to treat oligorecurrences may be very helpful. We successfully
      treated an 87-year-old patient who had been diagnosed with oligorecurrences three
      times over six years with radiotherapy alone. The patient is now, about four
      years after his first radiotherapy for liver metastasis, alive without any
      evidence of cancer and with fully active performance status. 

PMID- 25568858
TI  - Immune mechanisms in acetaminophen-induced acute liver failure.
AB  - An overdose of acetaminophen (N-acetyl-p-aminophenol, APAP), also termed
      paracetamol, can cause severe liver damage, ultimately leading to acute liver
      failure (ALF) with the need of liver transplantation. APAP is rapidly taken up
      from the intestine and metabolized in hepatocytes. A small fraction of the
      metabolized APAP forms cytotoxic mitochondrial protein adducts, leading to
      hepatocyte necrosis. The course of disease is not only critically influenced by
      dose of APAP and the initial hepatocyte damage, but also by the inflammatory
      response following acetaminophen-induced liver injury (AILI). As revealed by
      mouse models of AILI and corresponding translational studies in ALF patients,
      necrotic hepatocytes release danger-associated-molecular patterns (DAMPs), which
      are recognized by resident hepatic macrophages, Kupffer cell (KC), and
      neutrophils, leading to the activation of these cells. Activated hepatic
      macrophages release various proinflammatory cytokines, such as TNF-alpha or IL
      1beta, as well as chemokines (e.g., CCL2) thereby further enhancing inflammation
      and increasing the influx of immune cells, like bone-marrow derived monocytes and
      neutrophils. Monocytes are mainly recruited via their receptor CCR2 and aggravate
      inflammation. Infiltrating monocytes, however, can mature into monocyte-derived
      macrophages (MoMF), which are, in cooperation with neutrophils, also involved in
      the resolution of inflammation. Besides macrophages and neutrophils, distinct
      lymphocyte populations, especially gammadelta T cells, are also linked to the
      inflammatory response following an APAP overdose. Natural killer (NK), natural
      killer T (NKT) and T cells possibly further perpetuate inflammation in AILI.
      Understanding the complex interplay of immune cell subsets in experimental models
      and defining their functional involvement in disease progression is essential to
      identify novel therapeutic targets for human disease. 

PMID- 25568860
TI  - Therapeutic targeting of liver inflammation and fibrosis by nanomedicine.
AB  - Nanomedicine constitutes the emerging field of medical applications for
      nanotechnology such as nanomaterial-based drug delivery systems. This technology
      may hold exceptional potential for novel therapeutic approaches to liver
      diseases. The specific and unspecific targeting of macrophages, hepatic stellate
      cells (HSC), hepatocytes, and liver sinusoidal endothelial cells (LSEC) using
      nanomedicine has been developed and tested in preclinical settings. These four
      major cell types in the liver are crucially involved in the complex sequence of
      events that occurs during the initiation and maintenance of liver inflammation
      and fibrosis. Targeting different cell types can be based on their capacity to
      ingest surrounding material, endocytosis, and specificity for a single cell type
      can be achieved by targeting characteristic structures such as receptors, sugar
      moieties or peptide sequences. Macrophages and especially the liver-resident
      Kupffer cells are in the focus of nanomedicine due to their highly efficient and
      unspecific uptake of most nanomaterials as well as due to their critical
      pathogenic functions during inflammation and fibrogenesis. The mannose receptor
      enables targeting macrophages in liver disease, but macrophages can also become
      activated by certain nanomaterials, such as peptide-modified gold nanorods
      (AuNRs) that render them proinflammatory. HSC, the main collagen-producing cells
      during fibrosis, are currently targeted using nanoconstructs that recognize the
      mannose 6-phosphate and insulin-like growth factor II, peroxisome proliferator
      activated receptor 1, platelet-derived growth factor (PDGF) receptor beta, or
      integrins. Targeting of the major liver parenchymal cell, the hepatocyte, has
      only recently been achieved with high specificity by mimicking apolipoproteins,
      naturally occurring nanoparticles of the body. LSEC were found to be targeted
      most efficiently using carboxy-modified micelles and their integrin receptors.
      This review will summarize important functions of these cell types in healthy and
      diseased livers and discuss current strategies of cell-specific targeting for
      liver diseases by nanomedicine. 

PMID- 25568861
TI  - Innate immune signaling and gut-liver interactions in non-alcoholic fatty liver
      disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the
      metabolic syndrome and covers a disease spectrum ranging from steatosis to
      inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The innate
      immune response in the liver plays an important role during NAFLD progression. In
      addition, changes in the intestinal microbial balance and bacterial translocation
      can further affect disease progression. Immune cells in the liver recognize cell
      damage or pathogen invasion with intracellular or surface-expressed pattern
      recognition receptors (PRRs), subsequently initiating signaling cascades that
      trigger the release of factors promoting the inflammatory response during NAFLD
      progression. Therefore, mechanisms by which cells of the immune system are
      activated and recruited into the liver and how these cells cause injury and
      stress are important for understanding the inflammatory response during NAFLD. 

PMID- 25568863
TI  - Hepatocellular carcinoma markers in the omics era: the glycomic analysis.
AB  - Recently, Kamiyama et al. performed N-glycan profile in hepatocellular carcinoma
      (HCC) using the quantitative N-glycomics procedure by way of glycoblotting
      technology and using an automated glycan purification system. The study showed
      significant differences of N-glycans profile between healthy volunteers and liver
      cancer patients. The glycomic approach showed us the usefulness of new tools for
      identification and application of a new biomarkers for cancer diagnosis and
      treatment. These findings reveal a new field for future markers discovery. 

PMID- 25568859
TI  - Cellular and molecular functions of hepatic stellate cells in inflammatory
      responses and liver immunology.
AB  - The liver is a central immunological organ. Liver resident macrophages, Kupffer
      cells (KC), but also sinusoidal endothelial cells, dendritic cells (DC) and other
      immune cells are involved in balancing immunity and tolerance against pathogens,
      commensals or food antigens. Hepatic stellate cells (HSCs) have been primarily
      characterized as the main effector cells in liver fibrosis, due to their capacity
      to transdifferentiate into collagen-producing myofibroblasts (MFB). More recent
      studies elucidated the fundamental role of HSC in liver immunology. HSC are not
      only the major storage site for dietary vitamin A (Vit A) (retinol, retinoic
      acid), which is essential for proper function of the immune system. This pericyte
      further represents a versatile source of many soluble immunological active
      factors including cytokines [e.g., interleukin 17 (IL-17)] and chemokines [C-C
      motif chemokine (ligand) 2 (CCL2)], may act as an antigen presenting cell (APC),
      and has autophagy activity. Additionally, it responds to many immunological
      triggers via toll-like receptors (TLR) (e.g., TLR4, TLR9) and transduces signals
      through pathways and mediators traditionally found in immune cells, including the
      Hedgehog (Hh) pathway or inflammasome activation. Overall, HSC promote rather
      immune-suppressive responses in homeostasis, like induction of regulatory T cells
      (Treg), T cell apoptosis (via B7-H1, PDL-1) or inhibition of cytotoxic CD8 T
      cells. In conditions of liver injury, HSC are important sensors of altered tissue
      integrity and initiators of innate immune cell activation. Vice versa, several
      immune cell subtypes interact directly or via soluble mediators with HSC. Such
      interactions include the mutual activation of HSC (towards MFB) and macrophages
      or pro-apoptotic signals from natural killer (NK), natural killer T (NKT) and
      gamma-delta T cells (gammadelta T-cells) on activated HSC. Current directions of
      research investigate the immune-modulating functions of HSC in the environment of
      liver tumors, cellular heterogeneity or interactions promoting HSC deactivation
      during resolution of liver fibrosis. Understanding the role of HSC as central
      regulators of liver immunology may lead to novel therapeutic strategies for
      chronic liver diseases. 

PMID- 25568864
TI  - Novel biomarkers for hepatocellular carcinoma surveillance: has the future
      arrived?
AB  - Hepatocellular carcinoma (HCC) remains a major cause of mortality in patients
      with chronic liver disease worldwide. Early detection of HCC is critical to
      providing effective treatment and can have a significant impact on survival. In
      addition, effective surveillance following hepatic resection or locoregional
      ablative therapy can identify early recurrence and optimize long-term outcomes.
      Currently available serum tumor markers, including alpha-fetoprotein (AFP), are
      characterized by low sensitivity in the detection of HCC. Advances in genomic,
      proteomic, metabolomic, and glycomic profiling may provide a means to identify
      unique molecular signatures and characterization of complex processes associated
      with HCC incidence and recurrence. The development of highly sensitive and
      specific serum biomarkers for HCC may greatly enhance early detection rates, risk
      assessment in treatment candidates, and identification of potential new targets
      for anticancer therapy. 

PMID- 25568865
TI  - ART and science in using transarterial chemoembolization for retreating patients
      with hepatocellular carcinoma.
AB  - Intermediate stage hepatocellular carcinoma (HCC) comprises of a highly
      heterogeneous patient population, both in terms of liver function and tumour
      burden. Transarterial chemoembolization (TACE) is the treatment of choice for
      this subgroup of patients, provided that liver function is relatively preserved.
      Not all patients respond to an initial session of TACE, and further session might
      impair liver function. The ART score consists of an increase of AST >25%,
      increase of Child-Pugh of one or two points and absence of radiological tumour
      response and helps identify patients that would not benefit from further TACE
      sessions. We critically appraise the use of this score, particularly in terms of
      patient selection and timing of calculation of its variables. Once sufficiently
      validated, it can become a safe, objective and accurate clinical tool in everyday
      practice. 

PMID- 25568866
TI  - TIE2-expressing monocytes: a possible cellular diagnostic and prognostic
      biomarker for hepatocellular carcinoma.

PMID- 25568868
TI  - Living legend in surgery: Professor Roger Williams.

PMID- 25568867
TI  - Laparoscopic pancreaticoduodenectomy.
AB  - Laparoscopic pancreaticoduodenectomy (LPD) is one of the most complex operations
      in general surgery. With the development and maturation of surgical technology,
      more and more of such surgeries have been reported each year. Five LPDs have been
      performed in our department in the past year. We have achieved very satisfying
      clinical results with very few complications. The average operation takes 6.5
      hours, which is significantly shorter compared to prior operations. In addition,
      the average hospitalization time was significantly shortened. Here we present a
      case report on one of the LPDs. 

PMID- 25568862
TI  - Immunomodulatory effects of transforming growth factor-beta in the liver.
AB  - Members of the transforming growth factor-beta (TGF-beta) family are potent
      regulatory cytokines that affect multiple cell types of the immune system
      mediating pro-inflammatory or anti-inflammatory responses. In the liver, TGF-beta
      is produced by a multitude of non-parenchymal liver cells including hepatic
      stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), Kupffer cells
      (KCs), and dendritic cells (DCs) as well as natural killer (NK) T cells among
      other hepatic lymphocytes. The effect of TGF-beta on other cells is highly
      versatile. In concert with other soluble factors, it controls the maturation,
      differentiation and activity of various T cell subsets that either prevent or
      actuate infections, graft-versus-host reactions, immune diseases, and cancer
      formation. During the last decades, it became evident that some TGFB1
      polymorphisms are associated with the pathogenesis of hepatic disease and that
      plasma TGF-beta is a suitable biomarker to detect liver lesions. Moreover, since
      TGF-beta has capacity to influence the quantity and quality of T cell subsets as
      well as their activity, it is obvious that a well-balanced TGF-beta activity is
      essential for liver homeostasis. In the present review, we highlight some pivotal
      functions of TGF-beta in hepatic immunobiology. We discuss its regulatory
      function on adaptive immunity, the impact on differentiation of various T cell
      subsets, its crosstalk with Toll like receptor signaling, and its contribution to
      functional impairment of the liver. 

PMID- 25568869
TI  - To learn and to share: Hepatobiliary, Pancreatic Surgery and Manuscript Writing
      Symposium.

PMID- 25568870
TI  - It is time to integrate conventional therapy by ozone therapy in type-2 diabetes
      patients.

PMID- 25568872
TI  - Measuring the sweet smell of success in diabetes management.

PMID- 25568871
TI  - Editorial on the original article entitled "Changes in diabetes-related
      complications in the United States, 1990-2010" published in the New England
      Journal of Medicine on April 17, 2014.
AB  - The paper entitled "Changes in diabetes-related complications in the United
      States, 1990-2010" published recently in the New England Journal of Medicine
      examined the spectrum of diabetes complications over the past 20 years based on a
      unique, nationally representative database in the Unites States. It was noted
      that although adults with diagnosis of diabetes have more than tripled between
      the years 1990 and 2010, the rates of all five major complications of diabetes
      have declined significantly with the greatest absolute declines being noted for
      acute myocardial infarction followed by stroke, lower-extremity amputation, end
      stage renal disease and finally the death from hyperglycemic crisis. The greatest
      declines in most of the diabetes-related complications were observed among
      elderly persons who are above the age of 75 years with the exception of end stage
      renal disease which declined only in younger people but not among elderly. These
      findings could be due to the fact that over the past years there have been great
      advancements with regards to creating diabetes education programs especially
      after the publication of many trials that looked at the importance of intensive
      versus conventional glucose control, along with the enhanced management of other
      associated risk factors such as blood pressure, lipid levels, and smoking
      cessation. 

PMID- 25568873
TI  - Complications of diabetes: progress, but significant challenges ahead.

PMID- 25568874
TI  - A look at the trend in diabetes-related complications in the U.S. over the past
      two decades: looking ahead.

PMID- 25568875
TI  - Recent advances in the development of anti-HER2 antibodies and antibody-drug
      conjugates.
AB  - Human epidermal growth factor receptor 2 (HER2)-targeted therapies have
      revolutionized the treatment of HER2-positive breast cancer, both in the
      metastatic and early stage settings. While trastuzumab and lapatinib had been the
      mainstays of treatment in combination with chemotherapy, innate and acquired
      resistance to these therapies occur. More recently, two additional HER2-directed
      therapies have been approved for HER2-positive breast cancer. Pertuzumab is a
      humanized monoclonal antibody that binds to the extracellular portion of the
      receptor on a domain distinct from the binding site of trastuzumab. The addition
      of pertuzumab to trastuzumab results in synergistic tumor cell inhibition and has
      been shown to significantly improve clinical outcomes for patients with HER2
      positive metastatic breast cancer (MBC) compared to trastuzumab plus chemotherapy
      alone. In addition, ado-trastuzumab emtansine (T-DM1), a novel antibody-drug
      conjugate linking trastuzumab with the cytotoxic maytansinoid, DM1, is an
      effective treatment for HER2-positive breast cancer that has progressed on other
      HER2-directed therapies. Both pertuzumab and T-DM1 are relatively well tolerated.
      This review presents the mechanisms of action as well as phase I, II and III
      clinical data describing the safety and efficacy of pertuzumab and T-DM1 for HER2
      positive breast cancer. 

PMID- 25568876
TI  - Clinical advances in the development of novel VEGFR2 inhibitors.
AB  - Angiogenesis inhibitors have produced significant advances in the treatment of
      several tumors including colorectal, lung, ovarian and renal carcinomas. These
      agents, however, modestly impact on the overall cure rate, and their activity is
      often limited because of the early outbreak of redundant pathways or resistance
      mechanisms. Moreover, no clear predictive factor has been identified for
      treatment selection in the clinic. Preclinical evidence suggest that antibodies
      targeting the vascular endothelial growth factor (VEGF) axis may exert their
      activity throughout the inhibition of VEGF receptor 2 (VEGFR2) phosphorylation, a
      key factor in the cancer angiogenic process. Among other molecules, ramucirumab,
      an intravenously administered, fully humanized monoclonal antibody (mAb)
      targeting the extracellular domain of the receptor, and apatinib, a potent oral
      inhibitor of the intracellular domain, are emerging as original antiangiogenic
      opportunities. This up-to-date review focuses on the development of VEGFR2
      inhibitors across multiple cancers and presents results of the most recent
      researches, ranging from early phase I studies to randomized phase III trials, in
      which those drugs have been tested as a single-agent or in combination with
      different chemotherapy regimens. 

PMID- 25568879
TI  - Professor Frank McCormick: K-Ras proteins offer new opportunities for therapeutic
      intervention against human cancers.

PMID- 25568880
TI  - Prof. Dongsheng Fan: turn off the amyotrophic lateral sclerosis's disease gene.

PMID- 25568877
TI  - Genome-wide association studies in neurology.
AB  - Genome-wide association studies (GWAS) are a powerful tool for understanding the
      genetic underpinnings of human disease. In this article, we briefly review the
      role and findings of GWAS in common neurological diseases, including Stroke,
      Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, migraine,
      amyotrophic lateral sclerosis, frontotemporal lobar degeneration, restless legs
      syndrome, intracranial aneurysm, human prion diseases and moyamoya disease. We
      then discuss the present and future implications of these findings with regards
      to disease prediction, uncovering basic biology, and the development of potential
      therapeutic agents. 

PMID- 25568878
TI  - Application of next-generation sequencing technologies in Neurology.
AB  - Genetic risk factors that underlie many rare and common neurological diseases
      remain poorly understood because of the multi-factorial and heterogeneous nature
      of these disorders. Although genome-wide association studies (GWAS) have
      successfully uncovered numerous susceptibility genes for these diseases, odds
      ratios associated with risk alleles are generally low and account for only a
      small proportion of estimated heritability. These results implicated that there
      are rare (present in <5% of the population) but not causative variants exist in
      the pathogenesis of these diseases, which usually have large effect size and
      cannot be captured by GWAS. With the decreasing cost of next-generation
      sequencing (NGS) technologies, whole-genome sequencing (WGS) and whole-exome
      sequencing (WES) have enabled the rapid identification of rare variants with
      large effect size, which made huge progress in understanding the basis of many
      Mendelian neurological conditions as well as complex neurological diseases. In
      this article, recent NGS-based studies that aimed to investigate genetic causes
      for neurological diseases, including Alzheimer's disease, Parkinson's disease,
      epilepsy, multiple sclerosis, stroke, amyotrophic lateral sclerosis and
      spinocerebellar ataxias, have been reviewed. In addition, we also discuss the
      future directions of NGS applications in this article. 

PMID- 25568881
TI  - Biostatistics and epidemiology models in gastrointestinal cancers.

PMID- 25568882
TI  - Special issue on kidney stone disease.

PMID- 25568883
TI  - Highlights of translational pediatrics 2015.

PMID- 25568884
TI  - Predicting College Success: The Relative Contributions of Five Social/Personality
      Factors, Five Cognitive/Learning Factors, and SAT Scores.
AB  - To-date, studies have examined simultaneously the relative predictive powers of
      two or three factors on GPA. The present study examines the relative powers of
      five social/personality factors, five cognitive/learning factors, and SAT scores
      to predict freshmen and non-freshmen (sophomores, juniors, seniors) academic
      success (i.e., GPA). The results revealed many significant predictors of GPA for
      both freshmen and non-freshmen. However, subsequent regressions showed that only
      academic self-efficacy, epistemic belief of learning, and high-knowledge
      integration explained unique variance in GPA (19%-freshmen, 23.2%-non-freshmen).
      Further for freshmen, SAT scores explained an additional unique 10.6% variance
      after the influences attributed to these three predictors was removed whereas for
      non-freshmen, SAT scores failed to explain any additional variance. These results
      highlight the unique and important contributions of academic self-efficacy,
      epistemic belief of learning and high-knowledge integration to GPA beyond other
      previously-identified predictors.

PMID- 25568886
TI  - Anesthesia Providers are Obligated to Give Patients the Alternatives to General
      Anesthesia when Obtaining Informed Consent.

PMID- 25568885
TI  - FROM BIAS TO BISEXUAL HEALTH DISPARITIES: ATTITUDES TOWARD BISEXUAL MEN AND WOMEN
      IN THE UNITED STATES.
AB  - PUROPSE: A newly emergent literature suggest that bisexual men and women face
      profound health disparities in comparison to both heterosexual and homosexual
      individuals. Additionally, bisexual individuals often experience prejudice,
      stigma, and discrimination from both gay/lesbian and straight communities, termed
      "biphobia." However, only limited research exists that empirically tests the
      extent and predictors of this double discrimination. The Bisexualities: Indiana
      Attitudes Survey (BIAS) was developed to test associations between biphobia and
      sexual identity. METHODS: Using standard techniques, we developed and
      administered a scale to a purposive online sample of adults from a wide range of
      social networking websites. We conducted exploratory factor analysis to refine
      scales assessing attitudes toward bisexual men and bisexual women, respectively.
      Using generalized linear modeling, we assessed relationships between BIAS scores
      and sexual identity, adjusting for covariates. RESULTS: Two separately gendered
      scales were developed, administered, and refined: BIAS-m (n=645), focusing on
      attitudes toward bisexual men; and BIAS-f (n=631), focusing on attitudes toward
      bisexual women. Across scales, sexual identity significantly predicted response
      variance. Lesbian/gay respondents had lower levels of bi-negative attitudes than
      their heterosexual counterparts (all p-values <.05); bisexual respondents had
      lower levels of bi-negative attitudes than their straight counterparts (all p
      values <.001); and bisexual respondents had lower levels of bi-negative attitudes
      than their lesbian/gay counterparts (all p-values <.05). Within racial/ethnic
      minority respondents, biracial/multiracial status was associated with lower bi
      negativity scores (all p-values <.05). CONCLUSION: This study provides important
      quantitative support for theories related to biphobia and double discrimination.
      Our findings provide strong evidence for understanding how stereotypes and stigma
      may lead to dramatic disparities in depression, anxiety, stress, and other health
      outcomes among bisexual individuals in comparison to their heterosexual and
      homosexual counterparts. Our results yield valuable data for informing social
      awareness and intervention efforts that aim to decrease bi-negative attitudes
      within both straight and gay/lesbian communities, with the ultimate goal of
      alleviating health disparities among bisexual men and women.

PMID- 25568887
TI  - Salvinorin A decreases mortality and improves neurological outcome in a neonatal
      mouse hypoxia model.

PMID- 25568888
TI  - Distinctive distribution of lymphocytes in unruptured and previously untreated
      brain arteriovenous malformation.
AB  - AIM: To test the hypothesis that lymphocyte infiltration in brain arteriovenous
      malformation (bAVM) is not associated with iron deposition (indicator of
      microhemorrhage). METHODS: Sections of unruptured, previously untreated bAVM
      specimens (n=19) were stained immunohistochemically for T-lymphocytes (CD3+), B
      lymphocytes (CD20+), plasma cells (CD138+) and macrophages (CD68+). Iron
      deposition was assessed by hematoxylin and eosin and Prussian blue stains.
      Superficial temporal arteries (STA) were used as control. RESULTS: Both T
      lymphocytes and macrophages were present in unruptured, previously untreated bAVM
      specimens, whereas few B cells and plasma cells were detected. Iron deposition
      was detected in 8 specimens (42%; 95% confidence interval =20-67%). The samples
      with iron deposition tended to have more macrophages than those without (666+/
      313 vs 478+/-174 cells/mm2; P=0.11). T-cells were clustered on the luminal side
      of the endothelial surface, on the vessel-wall, and in the perivascular regions.
      There was no correlation between T lymphocyte load and iron deposition (P=0.88).
      No macrophages and lymphocytes were detected in STA controls. CONCLUSIONS: T
      lymphocytes were present in bAVM specimens. Unlike macrophages, the load and
      location of T-lymphocytes were not associated with iron deposition, suggesting
      the possibility of an independent cell-mediated immunological mechanism in bAVM
      pathogenesis.

PMID- 25568889
TI  - Interobserver and intermodality variability in GTV delineation on simulation CT,
      FDG-PET, and MR Images of Head and Neck Cancer.
AB  - PURPOSE: To compare the interobserver and intermodality differences in image
      based identification of head and neck primary site gross tumor volumes (GTV).
      Modalities compared include: contrast-enhanced CT, F-18 fluorodeoxyglucose
      positron emission tomography (PET/CT) and contrast-enhanced MRI. METHODS AND
      MATERIALS: Fourteen patients were simulated after immobilization for all 3
      imaging modalities (CT, PET/CT, MRI). Three radiation oncologists (RO) contoured
      GTVs as seen on each modality. The GTV was contoured first on the contrast
      enhanced CT (considered the standard), then on PET/CT, and finally on post
      contrast T1 MRI. Interobserver and intermodality variability were analyzed by
      volume, intersection, union, and volume overlap ratio (VOR). RESULTS: Analysis of
      RO contours revealed the average volume for CT-, PET/CT-, and MRI-derived GTVs
      were 45cc, 35cc and 49cc, respectively. In 93% of cases PET/CT-derived GTVs had
      the smallest volume and in 57% of cases MRI-derived GTVs had the largest volume.
      CT showed the largest variation in target definition (standard deviation amongst
      observers 35%) compared to PET/CT (28%) and MRI (27%). The VOR was largest
      (indicating greatest interobserver agreement) in PET/CT (46%), followed by MRI
      (36%), followed by CT (34%). For each observer, the least agreement in GTV
      definition occurred between MRI & PET/CT (average VOR = 41%), compared to CT &
      PET/CT (48%) and CT & MRI (47%). CONCLUSIONS: A nonsignificant interobserver
      difference in GTVs for each modality was seen. Among three modalities, CT was
      least consistent, while PET/CT-derived GTVs had the smallest volumes and were
      most consistent. MRI combined with PET/CT provided the least agreement in GTVs
      generated. The significance of these differences for head & neck cancer is
      important to explore as we move to volume-based treatment planning based on multi
      modality imaging as a standard method for treatment delivery.

PMID- 25568890
TI  - Intervention Approaches for Addressing Breast Cancer Disparities among African
      American Women.
AB  - African American women in the U.S. have a higher mortality rate from breast
      cancer than white women. Black-white differences in survival persist even after
      accounting for disease stage and tumor characteristics suggesting that the higher
      rates of breast cancer mortality are due to social factors. Several factors may
      account for racial differences in breast cancer mortality including socioeconomic
      factors, access to screening mammography and timely treatment, and biological
      factors. Efforts to prevent deaths from breast cancer and to address breast
      cancer disparities have focused on early detection through routine mammography
      and timely referral for treatment. There is a need for culturally appropriate,
      tailored health messages for African American women to increase their knowledge
      and awareness of health behaviors for the early detection of breast cancer.
      Several promising intervention approaches are reviewed in this article including:
      1) the use of cell phone text messaging and smart phone apps to increase breast
      cancer screening; 2) the use of radio stations that target African American
      audiences ("black radio") for health promotion activities; and 3) church-based
      behavioral interventions to promote breast cancer screening among African
      American women.

PMID- 25568891
TI  - Acculturation and Subclinical Atherosclerosis among U.S. South Asians: Findings
      from the MASALA study.
AB  - OBJECTIVE: Longer duration of residence among immigrants to the United States, a
      proxy measure of acculturation, has been associated with higher subclinical
      atherosclerosis. South Asian immigrants are the second fastest growing immigrant
      group in the U.S. but little is known about the effects of acculturation with
      atherosclerosis in this high cardiovascular risk population. METHODS: We
      conducted a cross-sectional analysis using data from a community-based cohort
      called the Mediators of Atherosclerosis in South Asians Living in America
      (MASALA) study. Participants (n=900) were between ages of 40-84 years and had no
      existing cardiovascular disease. We developed a multi-dimensional measure of
      acculturation in South Asians, called traditional cultural beliefs, and measured
      other proxy measures of acculturation to determine whether they were associated
      with higher levels of subclinical atherosclerosis after controlling for
      socioeconomic, behavior/lifestyle, and cardiovascular risk factors. RESULTS: Mean
      duration of residence in the U.S. was 27+/-11 years and tertiles of strength of
      traditional cultural beliefs were examined. Longer duration of U.S. residence was
      associated with higher levels of coronary artery calcium even after adjustment
      for covariates and lifestyle mediators. The novel measure of strength of
      traditional cultural beliefs was associated with lower common carotid intima
      media thickness among those with moderate traditional beliefs only. CONCLUSIONS:
      These findings support the need for better conceptualization and measurement of
      how migration influences cultural beliefs and practices, and their subsequent
      influence on health behaviors and cardiovascular disease risk.

PMID- 25568893
TI  - Readiness to change and gender: Moderators of the relationship between social
      desirability and college drinking.
AB  - This study evaluates the influence of readiness to change (RTC) and gender in the
      relationship between social desirability (SD) and drinking among college
      students. Need to avoid social disapproval may lead to underreporting of
      stigmatized behavior and as such, we expected that SD (Crowne & Marlowe, 1960)
      would negatively associate with drinking. Further, we sought to facilitate
      understanding of mixed findings in the RTC literature by parsing out effects
      separately for the precontemplation, contemplation, and action stage, as measured
      via three validated subscales of the RTC questionnaire (Rollnick et al., 1992).
      Motivational enhancement efforts tend to focus on increasing RTC among drinkers
      in the precontemplation and contemplation stage (e.g., Miller & Rollnick, 1992)
      as these individuals have not yet begun to engage in behavior change, and as
      such, we will focus on these two subscales. Based on the mixed literature, we
      hypothesized that RTC would be differentially associated with drinking for
      precontemplators and contemplators. Moreover, we considered gender and RTC as
      moderators of the effect of SD on drinking and expected that moderating effects
      would be different for precontemplators relative to contemplators. Participants
      included 676 undergraduate students (M age = 22.92, SD = 5.43, 82.44% female).
      Findings supported predictions. RTC was differentially associated with drinking;
      for precontemplators, RTC negatively predicted drinking, whereas for
      contemplators RTC positively predicted drinking, and effects were different for
      each gender. Hierarchical regressions revealed multiple two- and three-way
      interactions between RTC, SD, and gender in predicting drinking. Implications of
      results are discussed.

PMID- 25568894
TI  - Methods for Increasing Recruitment and Retention of Ethnic Minorities in Health
      Research Through Addressing Ethical Concerns.

PMID- 25568895
TI  - Infrared imaging of MDA-MB-231 breast cancer cell line phenotypes in 2D and 3D
      cultures.
AB  - One current challenge in the field of breast cancer infrared imaging is the
      identification of carcinoma cell subtypes in the tissue. Neither sequencing nor
      immunochemistry is currently able to provide a cell by cell thorough
      classification. The latter is needed to build accurate statistical models capable
      of recognizing the diversity of breast cancer cell lines that may be present in a
      tissue section. One possible approach for overcoming this problem is to obtain
      the IR spectral signature of well-characterized tumor cell lines in culture.
      Cultures in three-dimensional matrices appear to generate an environment that
      mimics better the in vivo environment. There are, at present, series of breast
      cancer cell lines that have been thoroughly characterized in two- and three
      dimensional (2D and 3D) cultures by full transcriptomics analyses. In this work,
      we describe the methods used to grow, to process, and to characterize a triple
      negative breast cancer cell line, MDA-MB-231, in 3D laminin-rich extracellular
      matrix (lrECM) culture and compare it with traditional monolayer cultures and
      tissue sections. While unsupervised analyses did not completely separate spectra
      of cells grown in 2D from 3D lrECM cultures, a supervised statistical analysis
      resulted in an almost perfect separation. When IR spectral responses of
      epithelial tumor cells from clinical triple-negative breast carcinoma samples
      were added to these data, a principal component analysis indicated that they
      cluster closer to the spectra of 3D culture cells than to the spectra of cells
      grown on a flat plastic substrata. This result is encouraging because of
      correlating well-characterized cell line features with clinical biopsies. 

PMID- 25568892
TI  - Cycle on Wheels: Is APP Key to the AppBp1 Pathway?
AB  - Alzheimer's disease (AD) is the gradual loss of the cognitive function due to
      neuronal death. Currently no therapy is available to slow down, reverse or
      prevent the disease. Here we analyze the existing data in literature and
      hypothesize that the physiological function of the Amyloid Precursor Protein
      (APP) is activating the AppBp1 pathway and this function is gradually lost during
      the progression of AD pathogenesis. The AppBp1 pathway, also known as the
      neddylation pathway, activates the small ubiquitin-like protein nedd8, which
      covalently modifies and switches on Cullin ubiquitin ligases, which are essential
      in the turnover of cell cycle proteins. Here we discuss how APP may activate the
      AppBp1 pathway, which downregulates cell cycle markers and protects genome
      integrity. More investigation of this mechanism-driven hypothesis may provide
      insights into disease treatment and prevention strategies.

PMID- 25568896
TI  - Complexation-flocculation combined with microwave-assisted headspace solid-phase
      microextraction in determining the binding constants of hydrophobic organic
      pollutants to dissolved humic substances.
AB  - The binding constants, KDOC, of selected polycyclic aromatic hydrocarbons (PAHs)
      phenanthrene, anthracene, fluoranthene, and pyrene-to dissolved humic substances
      (DHS) were determined by complexation-flocculation combined with microwave
      assisted headspace solid-phase microextraction (CF-MA-HS-SPME). The results
      obtained are comparable with KDOC data reported in the literature. No disruption
      of the PAH to DHS binding equilibrium was observed during the complexation
      flocculation process. The present study, which is the first to determine KDOC by
      CF-MA-HS-SPME, provides an alternative approach to determine the KDOC of PAHs. CF
      MA-HS-SPME provides some advantages over other methods, such as no limitation of
      fluorescent compounds, greater determination speed, and the capability of
      measuring various compounds simultaneously. 

PMID- 25568897
TI  - A facile fabrication of copper particle-decorated novel graphene flower
      composites for enhanced detecting of nitrite.
AB  - We describe a simple electrochemical preparation method of a novel three
      dimensional (3D) graphene material, porous flower-like reduced graphene oxide (f
      RGO) nanosheets, which was explored as the support for Cu particles on a glassy
      carbon electrode (Cu/f-RGO/GCE) for detecting nitrite. In morphology studies,
      scanning electron microscopy (SEM) demonstrates the 3D porous structure of f-RGO
      enlarges the surface area of the electrode and promotes more Cu particles
      depositing on the surface of f-RGO with homogeneous dispersion. In cyclic
      voltammetry (CV), a well-defined voltammetric peak along with the remarkable
      reduction current indicates excellent electrocatalytic activity of the Cu/f
      RGO/GCE for NaNO2 reduction compared with other corresponding electrodes. The
      effects of pH value and detection potential on the current responses of Cu/f
      RGO/GCE towards nitrite were optimized to obtain the maximal sensitivity. In the
      optimal experimental conditions, Cu/f-RGO/GCE displays the wide detection range
      from 0.15 MUM to 10,500 MUM and the low limit of detection of 0.06 MUM (S/N = 3)
      with fast response time 2 s for detecting NaNO2 through an amperometric method.
      Furthermore, the presence of K(+), Na(+), Cl(-), NH4(+), NO3(-), SO4(2-) and
      ascorbic acid show a negligible effect on the current response of nitrite
      determination suggesting Cu/f-RGO/GCE have the high selectivity for detecting
      nitrite even in the presence of high concentration of interferents. Moreover, the
      real sample determination experiment indicated practical feasibility of the
      obtained sensor. The prepared sensor for determination of NaNO2 exhibited wide
      liner range, low detection limit, good reproducibility, nice stability and
      remarkable anti-interference ability. In this paper, not only did the Cu/f
      RGO/GCE show high performance for determination of nitrite, but also it was
      simple to prepare, user-friendly and cost-effective.

PMID- 25568898
TI  - A uniform 2,5-dihydroxybenzoic acid layer as a matrix for MALDI-FTICR MS-based
      lipidomics.
AB  - A very uniform 2,5-dihydroxybenzoic acid (DHB) layer was for the first time
      constructed and used as a matrix for matrix-assisted laser desorption ionization
      Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) for
      quickly exploring the changes in lipids within biological systems. Lipid extracts
      from biological samples were dissolved in chloroform and deposited onto the DHB
      layer. Benefiting from the insolubility of DHB in chloroform, the uniform matrix
      crystals were still maintained, and more importantly, the lipid analytes were
      distributed homogeneously on the layer, which significantly increased the
      reproducibility of analysis using MALDI-FTICR MS. Taking advantage of the benefit
      of high resolution of FTICR MS and the fragment ions obtained by MS/MS, lots of
      lipids were identified. This method was used for exploring the changes of lipids
      in drug-resistant tumor cells compared with paired drug-sensitive tumor cells.
      The principal component analysis (PCA) and partial least-squares discriminant
      analysis (PLS-DA) were employed for discovery of the changed lipids. This method,
      characterized by the simplicity and the speediness, demonstrated a new and
      promising approach for lipidomics study. 

PMID- 25568899
TI  - A new sample preparation method for the absolute quantitation of a target
      proteome using (18)O labeling combined with multiple reaction monitoring mass
      spectrometry.
AB  - A key step in the workflow of bottom-up proteomics is the proteolysis of proteins
      into peptides with trypsin. In addition, enzyme-catalytic (18)O labeled peptides
      as internal standards coupled with multiple reaction monitoring mass spectrometry
      (MRM MS) for the absolute quantitation of the target proteome is commonly used
      for its convenient operation and low cost. However, long digestion and labeling
      times, incomplete digestion and (18)O to (16)O back exchange limit its
      application, therefore, we developed a rapid and efficient digestion method based
      on a high ratio of trypsin to protein. In addition, after separation of the
      digested samples using pipette tips packed with reversed-phase packing materials
      in house, the trypsin can be separated, collected and reused at least four times.
      Based on this approach, a novel protein quantification method using (18)O-labeled
      QconCAT peptides as internal standards combined with MRM MS for the absolute
      quantitation of a target proteome is established. Experimental results showed
      that the novel method had high digestion and (18)O labeling efficiencies, and no
      (18)O to (16)O back-exchange occurred. A linear range covering 2 orders of
      magnitude and a limit of quantification (LOQ) as low as 5 fmol were achieved with
      an RSD below 10%. Then, the quantitative method is used for the absolute
      quantitation of drug metabolizing enzymes in human liver microsomes. The results
      are in good agreement with the previously reported data, which demonstrates that
      the novel method can be used for absolute quantitative analyses of target
      proteomes in complex biological samples. 

PMID- 25568900
TI  - Label-free imaging and identification of typical cells of acute myeloid leukaemia
      and myelodysplastic syndrome by Raman microspectroscopy.
AB  - In clinical practice, the diagnosis and classification of acute myeloid leukaemia
      (AML) and myelodysplastic syndrome (MDS) start from the manual examination of
      stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical
      microscope. This step is subjective and scarcely reproducible. Therefore, the
      development of subjective and potentially automatable methods for the recognition
      of typical AML/MDS cells is necessary. Here we have used Raman spectroscopy for
      distinguishing myeloblasts, promyelocytes, abnormal promyelocytes and
      erhytroblasts, which have to be counted for a correct diagnosis and morphological
      classification of AML and MDS. BM samples from patients affected by four
      different AML subtypes, mostly characterized by the presence of the four
      subpopulations selected for this study, were analyzed. First, each cell was
      scanned by acquiring 4096 spectra, thus obtaining Raman images which demonstrate
      an accurate description of morphological features characteristic of each
      subpopulation. Raman imaging coupled with hierarchical cluster analysis permitted
      the automatic discrimination and localization of the nucleus, the cytoplasm,
      myeloperoxidase containing granules and haemoglobin. Second, the averaged Raman
      fingerprint of each cell was analysed by multivariate analysis (principal
      component analysis and linear discriminant analysis) in order to study the
      typical vibrational features of each subpopulation and also for the automatic
      recognition of cells. The leave-one-out cross validation of a Raman-based
      classification model demonstrated the correct classification of myeloblasts,
      promyelocytes (normal/abnormal) and erhytroblasts with an accuracy of 100%.
      Normal and abnormal promyelocytes were distinguished with 95% accuracy. The
      overall classification accuracy considering the four subpopulations was 98%. This
      proof-of-concept study shows that Raman micro-spectroscopy could be a valid
      approach for developing label-free, objective and automatic methods for the
      morphological classification and counting of cells from AML/MDS patients, in
      substitution of the manual examination of BM and PB stained smears. 

PMID- 25568901
TI  - Covalent coupling via dehalogenation on Ni(111) supported boron nitride and
      graphene.
AB  - Polymerization of 1,3,5-tris(4-bromophenyl)benzene via dehalogenation on graphene
      and hexagonal boron nitride is investigated by scanning tunneling microscopy
      experiments and density functional theory calculations. This work reveals how the
      interactions between molecules and graphene or h-BN grown on Ni(111) govern the
      surface-confined synthesis of polymers through C-C coupling. 

PMID- 25568902
TI  - [Deep Brain Stimulation - an effective therapy not only for Parkinson's disease].

PMID- 25568903
TI  - Author reply: To PMID 24800623.

PMID- 25568904
TI  - Author reply: To PMID 24800623.

PMID- 25568905
TI  - Preface. Agrobacterium protocols.

PMID- 25568906
TI  - Transitional cell carcinoma of the renal pelvis on presacral ectopic kidney.

PMID- 25568907
TI  - An embryological diagnosis in the elderly.

PMID- 25568908
TI  - Fascia-sparing intrafascial nerve-sparing robot-assisted radical prostatectomy
      and anatomic vesicourethral anastomosis: point of technique.
AB  - OBJECTIVES: Nerve-sparing radical prostatectomies provide excellent control of
      cancer, but the recovery of continence and sexual function are uncertain. We
      report the operative details and surgical techniques of a robot-assisted radical
      prostatectomy (RARP) experiences for organ confined prostate cancer. METHODS:
      Between the years of 2009 and 2012, 68 patients with clinically localized
      prostate cancer underwent fascia-sparing intrafascial nerve-sparing robot
      assisted radical prostatectomy and anatomic vesicourethral anastomosis. None of
      the patients were incontinent. 48 of them had an IIEF-5 potency score equal or
      greater than 22, without receiving phosphodiesterase-5 inhibitors. Our techniques
      included preservation of the bladder neck, preservation of the endopelvic fascia
      and puboprostatic ligaments, a nerve-sparing intrafascial approach, selective
      suturing of the dorsal venous complex, and anterior and posterior reconstruction.
      We evaluated the patients at the 1st, 3rd, 6th, and 12th postoperative months to
      determine if these techniques are correlated with early recovery of urinary
      continence and potency. RESULTS: The mean operation time was 258.2+/-78.5
      minutes, and the mean estimated blood loss was 111.2+/-22.9 cc during the
      operation. A nerve-sparing procedure was performed bilaterally in 62 (91.2 %)
      cases and unilaterally in 6 (8.8%) cases. The mean drain extraction time was
      2.3+/-0.9 days, and the mean hospital stay was 3.4+/-1.1 days. The catheter was
      removed on postoperative day 9.9+/-0.9. The surgical margin was positive in 10
      (14.7%) patients. The continence rates at 1, 3, 6, and 12 months were 74.2%,
      76.9%, 80.6%, and 95.6%, respectively. During the same period, among the patients
      without ED, the potency rates were 29.4%, 38.2%, 54.1%, and 75%, respectively All
      operations were completed successfully, and there were no major complications.
      CONCLUSIONS: A more comprehensive approach for reporting prostate cancer surgery
      outcomes is needed. Our study findings suggest that fascia-sparing techniques
      positively influence the early recovery of urinary continence. However,
      randomized controlled trials with large samples are needed.

PMID- 25568909
TI  - Refining electrocardiography interpretation criteria in elite athletes:
      redefining the limits of normal.

PMID- 25568910
TI  - Performance enhancing agents and the heart.

PMID- 25568911
TI  - Sudden cardiac death in young competitive athletes.

PMID- 25568912
TI  - Fit teenagers are less likely to have myocardial infarctions in later life.

PMID- 25568913
TI  - Remote ischaemic preconditioning: the missing link between  bench and bedside.

PMID- 25568914
TI  - [Breast cancer detection by ultrasound screening in dense breast tissue].

PMID- 25568915
TI  - [Influence of standardized communication training for oncologists on quality of
      bad news transmission].

PMID- 25568916
TI  - Hopes for the year ahead.

PMID- 25568917
TI  - Data mining in clinical medicine. Preface.

PMID- 25568918
TI  - The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in
      cancer.
AB  - The TYRO3, AXL (also known as UFO) and MERTK (TAM) family of receptor tyrosine
      kinases (RTKs) are aberrantly expressed in multiple haematological and epithelial
      malignancies. Rather than functioning as oncogenic drivers, their induction in
      tumour cells predominately promotes survival, chemoresistance and motility. The
      unique mode of maximal activation of this RTK family requires an extracellular
      lipid-protein complex. For example, the protein ligand, growth arrest-specific
      protein 6 (GAS6), binds to phosphatidylserine (PtdSer) that is externalized on
      apoptotic cell membranes, which activates MERTK on macrophages. This triggers
      engulfment of apoptotic material and subsequent anti-inflammatory macrophage
      polarization. In tumours, autocrine and paracrine ligands and apoptotic cells are
      abundant, which provide a survival signal to the tumour cell and favour an anti
      inflammatory, immunosuppressive microenvironment. Thus, TAM kinase inhibition
      could stimulate antitumour immunity, reduce tumour cell survival, enhance
      chemosensitivity and diminish metastatic potential.

PMID- 25568919
TI  - Hypermutation in human cancer  genomes: footprints and mechanisms.
AB  - A role for somatic mutations in carcinogenesis is well accepted, but the degree
      to which mutation rates influence cancer initiation and development is under
      continuous debate. Recently accumulated genomic data have revealed that thousands
      of tumour samples are riddled by hypermutation, broadening support for the idea
      that many cancers acquire a mutator phenotype. This major expansion of cancer
      mutation data sets has provided unprecedented statistical power for the analysis
      of mutation spectra, which has confirmed several classical sources of mutation in
      cancer, highlighted new prominent mutation sources (such as apolipoprotein B mRNA
      editing enzyme catalytic polypeptide-like (APOBEC) enzymes) and empowered the
      search for cancer drivers. The confluence of cancer mutation genomics and
      mechanistic insight provides great promise for understanding the basic
      development of cancer through mutations.

PMID- 25568921
TI  - Tumour evolution: clonal ancestry in lung cancer.

PMID- 25568922
TI  - Microenvironment: small containers, important cargo.

PMID- 25568923
TI  - Tumour immunology: anticancer drugs copy bugs.

PMID- 25568920
TI  - Aryl hydrocarbon receptor ligands  in cancer: friend and foe.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      that is best known for mediating the toxicity and tumour-promoting properties of
      the carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly referred to as
      'dioxin'. AHR influences the major stages of tumorigenesis - initiation,
      promotion, progression and metastasis - and physiologically relevant AHR ligands
      are often formed during disease states or during heightened innate and adaptive
      immune responses. Interestingly, ligand specificity and affinity vary between
      rodents and humans. Studies of aggressive tumours and tumour cell lines show
      increased levels of AHR and constitutive localization of this receptor in the
      nucleus. This suggests that the AHR is chronically activated in tumours, thus
      facilitating tumour progression. This Review discusses the role of AHR in
      tumorigenesis and the potential for therapeutic modulation of its activity in
      tumours.

PMID- 25568925
TI  - Cancer epigenetics: risk assessment, diagnosis, treatment, and prognosis.
      Preface.

PMID- 25568924
TI  - Geographic divergence of bovine and human Shiga toxin-producing Escherichia coli
      O157:H7 genotypes, New Zealand.
AB  - Shiga toxin-producing Escherichia coli (STEC)O157:H7 is a zoonotic pathogen of
      public health concern worldwide. To compare the local and large-scale geographic
      distributions of genotypes of STEC O157:H7 isolates obtained from various bovine
      and human sources during 2008-2011, we used pulsed-field gel electrophoresis and
      Shiga toxin-encoding bacteriophage insertion (SBI) typing. Using multivariate
      methods, we compared isolates from the North and South Islands of New Zealand
      with isolates from Australia and the United States. The STEC O157:H7 population
      structure differed substantially between the 2 islands and showed evidence of
      finer scale spatial structuring, which is consistent with highly localized
      transmission rather than disseminated foodborne outbreaks. The distribution of
      SBI types differed markedly among isolates from New Zealand, Australia, and the
      United States. Our findings also provide evidence for the historic introduction
      into New Zealand of a subset of globally circulating STEC O157:H7 strains that
      have continued to evolve and be transmitted locally between cattle and humans.

PMID- 25568927
TI  - Hepatitis E virus in young pigs in Finland and characterization of the isolated
      partial genomic sequences of genotype 3 HEV.
AB  - Hepatitis E virus (HEV) infections occur in swine worldwide. The porcine
      infection is usually subclinical, but HEV genotypes 3 and 4 are zoonotic agents
      that cause sporadic, indigenous human cases of hepatitis E. The aims of this
      study were to investigate the occurrence and dynamics of HEV infections in young
      pigs by analyzing a total of 273 fecal samples collected from six farrowing
      farms, to genetically characterize the HEV isolates obtained, and to examine the
      phylogenetic relationships of HEV isolates occurring at different swine farms in
      Finland. Fecal shedding of HEV of individual piglets was followed at two farms
      that were selected from five farms identified as HEV RNA positive. Excretion of
      HEV was detected in 87.5% of the piglets during the survey. Piglets contracted
      primary HEV infection 3-8 weeks after weaning, and at the time they were
      transferred to fattening farms, practically all (96.6%) of the pigs with a sample
      available at this occasion still excreted the virus. According to phylogenetic
      analysis, all HEV isolates obtained belonged to HEV genotype 3, subtype e, and a
      separate, farm-specific isolate originated from 10 of 11 farms examined. The
      results of our study show that HEV infections are highly common in young pigs,
      and HEV RNA-positive pigs enable HEV transmission from farrowing to fattening
      farms, creating a possible risk of infection for pig handlers, and that genetic
      variations in HEVs originating from different farms occur. 

PMID- 25568928
TI  - Oleanane triterpenes from the flowers of Camellia japonica inhibit porcine
      epidemic diarrhea virus (PEDV) replication.
AB  - Porcine epidemic diarrhea virus (PEDV) infections have resulted in a severe
      economic loss in the swine industry in many countries due to no effective
      treatment approach. Fifteen oleanane triterpenes (1-15), including nine new ones
      (1-4 and 10-14), were isolated from the flowers of Camellia japonica, and their
      molecular structures were determined by extensive spectroscopic methods. These
      compounds were evaluated for their antiviral activity against PEDV replication,
      and the structure-activity relationships (SARs) were discussed. Compounds 6, 9,
      11, and 13 showed most potent inhibitory effects on PEDV replication. They were
      found to inhibit PEDV genes encoding GP6 nucleocapsid, GP2 spike, and GP5
      membrane protein synthesis based on RT-PCR data. Western blot analysis also
      demonstrated their inhibitory effects on PEDV GP6 nucleocapsid and GP2 spike
      protein synthesis during viral replication. The present study suggested the
      potential of compounds 6, 9, 11, and 13 as promising scaffolds for treating PEDV
      infection via inhibiting viral replication. 

PMID- 25568926
TI  - The Regulation of Proresolving Lipid Mediator Profiles in Baboon Pneumonia by
      Inhaled Carbon Monoxide.
AB  - Strategies for the treatment of bacterial pneumonia beyond traditional
      antimicrobial therapy have been limited. The recently discovered novel genus of
      lipid mediators, coined "specialized proresolving mediators" (SPMs), which
      orchestrate clearance of recruited leukocytes and restore epithelial barrier
      integrity, have offered new insight into the resolution of inflammation. We
      performed lipid mediator (LM) metabololipidomic profiling and identification of
      LMs on peripheral blood leukocytes and plasma from a baboon model of
      Streptococcus pneumoniae pneumonia. Leukocytes and plasma were isolated from
      whole blood of S. pneumoniae-infected (n = 5-6 per time point) and control,
      uninfected baboons (n = 4 per time point) at 0, 24, 48, and 168 hours. In a
      subset of baboons with pneumonia (n = 3), we administered inhaled carbon monoxide
      (CO) at 48 hours (200-300 ppm for 60-90 min). Unstimulated leukocytes from
      control animals produced a proresolving LM signature with elevated resolvins and
      lipoxins. In contrast, serum-treated, zymosan-stimulated leukocytes and
      leukocytes from baboons with S. pneumoniae pneumonia produced a proinflammatory
      LM signature profile with elevated leukotriene B4 and prostaglandins. Plasma from
      baboons with S. pneumoniae pneumonia also displayed significantly reduced LM-SPM
      levels, including eicosapentaenoic acid-derived E-series resolvins (RvE) and
      lipoxins. CO inhalation increased levels of plasma RvE and lipoxins relative to
      preexposure levels. These results establish the leukocyte and plasma LM profiles
      biosynthesized during S. pneumoniae pneumonia in baboons and provide evidence for
      pneumonia-induced dysregulation of these proresolution programs. Moreover, these
      SPM profiles are partially restored with inhaled low-dose CO and SPM, which may
      shorten the time to pneumonia resolution. 

PMID- 25568931
TI  - Genetic influence on the reduction in bovine embryo lipid content by l-carnitine.
AB  - The decreased rate of pregnancy obtained in cattle using frozen in vitro embryos
      compared with in vivo embryos has been associated with over-accumulation of
      intracellular lipid, which causes cell damage during cryopreservation. It is
      believed that the higher lipid content of blastomeres of bovine embryos produced
      in vitro results in darker-coloured cytoplasm, which could be a consequence of
      impaired mitochondrial function. In this study, l-carnitine was used as a
      treatment to reduce embryonic lipid content by increasing metabolism in cultured
      bovine embryos. We have observed previously that in vivo embryos of different
      dairy breeds collected from cows housed and fed under the same conditions
      differed in lipid content and metabolism. As such, breed effects between Holstein
      and Jersey were also examined in terms of general appearance, lipid composition,
      mitochondrial activity and gene expression. Adding l-carnitine to the embryo
      culture medium reduced the lipid content in both breeds due to increased
      mitochondrial activity. The response to l-carnitine was weaker in Jersey than in
      Holstein embryos. Our results thus show that genetics influence the response of
      bovine embryos to stimulation of mitochondrial metabolism.

PMID- 25568930
TI  - Effects of high CO2 levels on fermentation, peroxidation, and cellular water
      stress in Fragaria vesca stored at low temperature in conditions of unlimited O2.
AB  - To better understand the tolerance of strawberries (Fragaria vesca L.) to high
      CO2 in storage atmospheres, fermentation and cellular damage were investigated.
      Fruits were stored for 3 and 6 days at 0  degrees C in the presence of different
      CO2 levels (0, 20, or 40%) with 20% O2. Changes in pyruvate decarboxylase (PDC)
      and alcohol dehydrogenase (ADH) gene expression and in fermentative metabolites,
      as well as in bound water and malondialdehyde (MDA) concentrations, were
      analyzed. In strawberries stored without added CO2, up-regulation of PDC and ADH
      was not associated with an increase in fermentative metabolites. By contrast,
      moderate ethanol fermentation in fruits exposed to 20% CO2 seems to be essential
      to maintain fruit metabolism, reducing both lipid peroxidation and cellular water
      stress. However, if the CO2 concentration increases (40%), the excess
      acetaldehyde and ethanol produced were closely correlated with a decrease in
      bound water and production of MDA. 

PMID- 25568929
TI  - Six-minute-walk distance and accelerometry predict outcomes in chronic
      obstructive pulmonary disease independent of Global Initiative for Chronic
      Obstructive Lung Disease 2011 Group.
AB  - RATIONALE: The 2011 combined Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) assessment incorporates symptoms, exacerbation history, and
      spirometry in discriminating risk of exacerbations in patients with chronic
      obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and
      accelerometry also have been used to assess disease severity in COPD. The
      association between these measures and the risks of hospitalization and mortality
      in the context of GOLD 2011 is unknown. OBJECTIVES: To describe changes in
      exercise tolerance and physical activity over time in patients with COPD and to
      test the hypothesis that lower baseline 6MWD or accelerometry step count is
      associated with increased risk of COPD-related hospitalization or all-cause
      mortality, independent of GOLD 2011 group. METHODS: Physical function and medical
      outcomes were prospectively assessed in 326 patients with moderate to severe COPD
      in INSPIRE-II, a randomized controlled trial of a coping skills training
      intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or
      accelerometry steps were associated with risk of COPD-related hospitalization or
      all-cause mortality. MEASUREMENTS AND MAIN RESULTS: Physical function declined
      over time in GOLD group D but remained stable in groups A, B, and C. GOLD
      classification was associated with time to death or first COPD-related
      hospitalization. Baseline 6MWD was more strongly associated with time to death or
      first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval,
      0.34, 0.73] per 150 m, P=0.0003) than GOLD 2011 classification. A similar
      relationship was observed for accelerometry steps (hazard ratio, 0.80 [95%
      confidence interval, 0.70, 0.92] per 1,000 steps, P=0.002). CONCLUSIONS: Exercise
      tolerance and daily physical activity are important predictors of hospitalization
      and mortality in COPD, independent of GOLD 2011 classification. Physical function
      may represent a modifiable risk factor that warrants increased attention as a
      target for interventions to improve clinically meaningful outcomes in COPD.

PMID- 25568932
TI  - Stable ferroelectric perovskite structure with giant axial ratio and polarization
      in epitaxial BiFe0.6Ga0.4O3 thin films.
AB  - Ferroelectric perovskites with strongly elongated unit cells (c/a > 1.2) are of
      particular interest for realizing giant polarization induced by significant ionic
      off-center displacements. Here we show that epitaxial BiFe0.6Ga0.4O3 (BFGO) thin
      films exhibit a stable super-tetragonal-like structure with twinning domains
      regardless of film thickness and substrate induced strain, evidenced with high
      resolution X-ray diffractometry (HR-XRD), transmission electron microscopy (TEM)
      and piezoresponse force microscopy (PFM). The origin of the structural stability
      of BFGO is investigated by the first-principles calculation. The ferroelectric
      properties of BFGO are studied by PFM, first-principles calculation and
      macroscopic polarization-electric field (P-E) hysteresis measurement. A giant
      ferroelectric polarization of ~150 MUC/cm(2) is revealed by the first-principles
      calculations and confirmed by experiments. Our studies provide an alternative
      pathway of employing Ga-substitution other than the extensively studied strain
      engineering to stabilize the supertetragonal structure in BiFeO3-based epitaxial
      thin films. 

PMID- 25568933
TI  - Bronsted acid catalyzed monoalkylation of anilines with trichloroacetimidates.
AB  - Trichloroacetimidates are useful alkylating agents for aromatic amines, requiring
      only a catalytic amount of a Bronsted acid to facilitate the reaction.
      Monoalkylation predominates under these conditions. Electron-poor anilines
      provide superior yields, with electron-rich anilines sometimes showing
      competitive Friedel-Crafts alkylation. A single flask protocol with formation of
      the imidate in situ is demonstrated, providing a convenient method for the direct
      substitution of alcohols with anilines. Reaction with a chiral imidate favors a
      mechanism that proceeds through a carbocation intermediate. 

PMID- 25568934
TI  - Tunable Hydrophilic or Amphiphilic Coatings: A "Reactive Layer Stack" Approach.
AB  - Thin films with tunable properties are very interesting for potential
      applications as functional coatings with, for example, anti-icing or improved
      easy-to-clean properties. A novel "reactive layer stack" approach was developed
      to create covalently grafted mono- and multilayers of poly(glycidyl
      methacrylate)/poly(tert-butyl acrylate) diblock copolymers. Because these
      copolymers contain poly(glycidyl methacrylate) blocks they behave as self-cross
      linking materials after creation of acrylic acid functionalities by splitting off
      the tert-butyl units. The ellipsometrically determined coating thickness of the
      resulting hydrophilic multilayers depended linearly on the number of applied
      layers. Amphiphilic films with tunable wettability were prepared using triblock
      terpolymers with an additional poly(methyl methacrylate) block. The mechanism of
      the formation of the (multi)layers was investigated in detail by studying the
      acidolysis of the surface-linked tert-butyl acrylate blocks by infrared
      reflection absorbance spectroscopy, accompanied by surface analysis using atomic
      force microscopy and contact angle measurements. In the case of the amphiphilic
      and switchable terpolymer layers this reaction was very sensitive to the used
      acidic reagent. 

PMID- 25568935
TI  - KRAS mutation analysis by PCR: a comparison of two methods.
AB  - BACKGROUND: KRAS mutation assays are important companion diagnostic tests to
      guide anti-EGFR antibody treatment of metastatic colorectal cancer. Direct
      comparison of newer diagnostic methods with existing methods is an important part
      of validation of any new technique. In this this study, we have compared the
      Therascreen (Qiagen) ARMS assay with Competitive Allele-Specific TaqMan PCR
      (castPCR, Life Technologies) to determine equivalence for KRAS mutation analysis.
      METHODS: DNA was extracted by Maxwell (Promega) from 99 colorectal cancers. The
      ARMS-based Therascreen and a customized castPCR assay were performed according to
      the manufacturer's instructions. All assays were performed on either an Applied
      Biosystems 7500 Fast Dx or a ViiA7 real-time PCR machine (both from Life
      Technologies). The data were collected and discrepant results re-tested with
      newly extracted DNA from the same blocks in both assay types. RESULTS: Of the 99
      tumors included, Therascreen showed 62 tumors to be wild-type (WT) for KRAS,
      while 37 had KRAS mutations on initial testing. CastPCR showed 61 tumors to be
      wild-type (WT) for KRAS, while 38 had KRAS mutations. Thirteen tumors showed BRAF
      mutation in castPCR and in one of these there was also a KRAS mutation. The
      custom castPCR plate included several other KRAS mutations and BRAF V600E, not
      included in Therascreen, explaining the higher number of mutations detected by
      castPCR. Re-testing of discrepant results was required in three tumors, all of
      which then achieved concordance for KRAS. CastPCR assay Ct values were on average
      2 cycles lower than Therascreen. CONCLUSION: There was excellent correlation
      between the two methods. Although castPCR assay shows lower Ct values than
      Therascreen, this is unlikely to be clinically significant.

PMID- 25568936
TI  - Analysis of individual protein regions provides novel insights on cancer
      pharmacogenomics.
AB  - The promise of personalized cancer medicine cannot be fulfilled until we gain
      better understanding of the connections between the genomic makeup of a patient's
      tumor and its response to anticancer drugs. Several datasets that include both
      pharmacologic profiles of cancer cell lines as well as their genomic alterations
      have been recently developed and extensively analyzed. However, most analyses of
      these datasets assume that mutations in a gene will have the same consequences
      regardless of their location. While this assumption might be correct in some
      cases, such analyses may miss subtler, yet still relevant, effects mediated by
      mutations in specific protein regions. Here we study such perturbations by
      separating effects of mutations in different protein functional regions (PFRs),
      including protein domains and intrinsically disordered regions. Using this
      approach, we have been able to identify 171 novel associations between mutations
      in specific PFRs and changes in the activity of 24 drugs that couldn't be
      recovered by traditional gene-centric analyses. Our results demonstrate how
      focusing on individual protein regions can provide novel insights into the
      mechanisms underlying the drug sensitivity of cancer cell lines. Moreover, while
      these new correlations are identified using only data from cancer cell lines, we
      have been able to validate some of our predictions using data from actual cancer
      patients. Our findings highlight how gene-centric experiments (such as systematic
      knock-out or silencing of individual genes) are missing relevant effects mediated
      by perturbations of specific protein regions. All the associations described here
      are available from http://www.cancer3d.org. 

PMID- 25568938
TI  - Characterization of heavy-metal-contaminated sediment by using unsupervised
      multivariate techniques and health risk assessment.
AB  - This study characterized the sediment quality of the severely contaminated Erjen
      River in Taiwan by using multivariate analysis methods-including factor analysis
      (FA), self-organizing maps (SOMs), and positive matrix factorization (PMF)-and
      health risk assessment. The SOMs classified the dataset with similar heavy-metal
      contaminated sediment into five groups. FA extracted three major factors
      traditional electroplating and metal-surface processing factor, nontraditional
      heavy-metal-industry factor, and natural geological factor-which accounted for
      80.8% of the variance. The SOMs and FA revealed the heavy-metal-contaminated
      sediment hotspots in the middle and upper reaches of the major tributary in the
      dry season. The hazardous index value for health risk via ingestion was 0.302.
      PMF further qualified the source apportionment, indicating that traditional
      electroplating and metal-surface-processing industries comprised 47% of the
      health risk posed by heavy-metal-contaminated sediment. Contaminants discharged
      from traditional electroplating and metal-surface-processing industries in the
      middle and upper reaches of the major tributary must be eliminated first to
      improve the sediment quality in Erjen River. The proposed assessment framework
      for heavy-metal-contaminated sediment can be applied to contaminated-sediment
      river sites in other regions. 

PMID- 25568937
TI  - PRDM9 drives evolutionary erosion of hotspots in Mus musculus through haplotype
      specific initiation of meiotic recombination.
AB  - Meiotic recombination generates new genetic variation and assures the proper
      segregation of chromosomes in gametes. PRDM9, a zinc finger protein with histone
      methyltransferase activity, initiates meiotic recombination by binding DNA at
      recombination hotspots and directing the position of DNA double-strand breaks
      (DSB). The DSB repair mechanism suggests that hotspots should eventually self
      destruct, yet genome-wide recombination levels remain constant, a conundrum known
      as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we
      measured activity of the Prdm9Cst allele in two Mus musculus subspecies, M.m.
      castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was
      introduced experimentally. Comparing these two strains, we find that haplotype
      differences at hotspots lead to qualitative and quantitative changes in PRDM9
      binding and activity. Using Mus spretus as an outlier, we found most variants
      affecting PRDM9Cst binding arose and were fixed in M.m. castaneus, suppressing
      hotspot activity. Furthermore, M.m. castaneus*M.m. domesticus F1 hybrids exhibit
      novel hotspots, with large haplotype biases in both PRDM9 binding and chromatin
      modification. These novel hotspots represent sites of historic evolutionary
      erosion that become activated in hybrids due to crosstalk between one parent's
      Prdm9 allele and the opposite parent's chromosome. Together these data support a
      model where haplotype-specific PRDM9 binding directs biased gene conversion at
      hotspots, ultimately leading to hotspot erosion. 

PMID- 25568939
TI  - Assessment of pesticide residues and gene expression in common carp exposed to
      atrazine and chlorpyrifos: Health risk assessments.
AB  - This study assessed the impacts of atrazine (ATR), chlorpyrifos (CPF) and
      combined ATR/CPF exposure on the kidney of common carp (Cyprinus carpio L.). The
      carp were sampled after a 40-d exposure to CPF and ATR, individually or in
      combination, followed by a 40-d recovery to measure the expression levels of heat
      shock proteins genes (HSP60, HSP70 and HSP90) and pesticide residues in the
      kidney tissue. The results revealed that the mRNA and protein levels of HSP60,
      HSP70 and HSP90 were induced in the kidney of common carp by ATR, CPF, and
      ATR/CPF mixture. The accumulated amounts of ATR, CPF, and their metabolites in
      the kidney tissues exhibited dose-dependency. These results exhibited that
      increasing concentration of ATR and CPF in the environment causes considerable
      stress for common carp, suggesting that the expression levels of HSP60, HSP70 and
      HSP90 may act as potential biomarkers for assessing the environmental ATR and CPF
      risk for carp. 

PMID- 25568940
TI  - The electronic circular dichroism of nicotine in aqueous solution: a test case
      for continuum and mixed explicit-continuum solvation approaches.
AB  - In this paper, we extend an integrated QM/MM/polarizable continuum model (PCM)
      method, which combines a fluctuating charge (FQ) approach to the MM polarization
      with the PCM, to describe electronic circular dichroism (ECD) spectra of systems
      in aqueous solution. The main features of the approach are presented, and then
      applications to the UV and ECD spectra of neutral (S)-nicotine in aqueous
      solution are reported. The performance of the QM/FQ/PCM is compared with that of
      the PCM against newly measured UV ECD spectra, which are in agreement with
      previous findings. The inclusion of specific solvation effects via the QM/FQ/PCM
      method leads to an improvement in the calculated spectra compared to the
      experimental findings, though the pure PCM results are still qualitatively
      correct and are a useful tool for the characterization of the states. 

PMID- 25568941
TI  - Ribose 5-phosphate isomerase B knockdown compromises Trypanosoma brucei
      bloodstream form infectivity.
AB  - Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of
      the pentose phosphate pathway, and catalyzes the inter-conversion of D-ribose 5
      phosphate and D-ribulose 5-phosphate. Trypanosomatids, including the agent of
      African sleeping sickness namely Trypanosoma brucei, have a type B ribose-5
      phosphate isomerase. This enzyme is absent from humans, which have a structurally
      unrelated ribose 5-phosphate isomerase type A, and therefore has been proposed as
      an attractive drug target waiting further characterization. In this study,
      Trypanosoma brucei ribose 5-phosphate isomerase B showed in vitro isomerase
      activity. RNAi against this enzyme reduced parasites' in vitro growth, and more
      importantly, bloodstream forms infectivity. Mice infected with induced RNAi
      clones exhibited lower parasitaemia and a prolonged survival compared to control
      mice. Phenotypic reversion was achieved by complementing induced RNAi clones with
      an ectopic copy of Trypanosoma cruzi gene. Our results present the first
      functional characterization of Trypanosoma brucei ribose 5-phosphate isomerase B,
      and show the relevance of an enzyme belonging to the non-oxidative branch of the
      pentose phosphate pathway in the context of Trypanosoma brucei infection. 

PMID- 25568943
TI  - Nicotiana small RNA sequences support a host genome origin of cucumber mosaic
      virus satellite RNA.
AB  - Satellite RNAs (satRNAs) are small noncoding subviral RNA pathogens in plants
      that depend on helper viruses for replication and spread. Despite many decades of
      research, the origin of satRNAs remains unknown. In this study we show that a
      beta-glucuronidase (GUS) transgene fused with a Cucumber mosaic virus (CMV) Y
      satellite RNA (Y-Sat) sequence (35S-GUS:Sat) was transcriptionally repressed in
      N. tabacum in comparison to a 35S-GUS transgene that did not contain the Y-Sat
      sequence. This repression was not due to DNA methylation at the 35S promoter, but
      was associated with specific DNA methylation at the Y-Sat sequence. Both northern
      blot hybridization and small RNA deep sequencing detected 24-nt siRNAs in wild
      type Nicotiana plants with sequence homology to Y-Sat, suggesting that the N.
      tabacum genome contains Y-Sat-like sequences that give rise to 24-nt sRNAs
      capable of guiding RNA-directed DNA methylation (RdDM) to the Y-Sat sequence in
      the 35S-GUS:Sat transgene. Consistent with this, Southern blot hybridization
      detected multiple DNA bands in Nicotiana plants that had sequence homology to Y
      Sat, suggesting that Y-Sat-like sequences exist in the Nicotiana genome as
      repetitive DNA, a DNA feature associated with 24-nt sRNAs. Our results point to a
      host genome origin for CMV satRNAs, and suggest novel approach of using small RNA
      sequences for finding the origin of other satRNAs. 

PMID- 25568942
TI  - Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive
      similarity to T. brucei and multiple independent origins for dyskinetoplasty.
AB  - Two key biological features distinguish Trypanosoma evansi from the T. brucei
      group: independence from the tsetse fly as obligatory vector, and independence
      from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an
      effort to better understand the molecular causes and consequences of these
      differences, we sequenced the genome of an akinetoplastic T. evansi strain from
      China and compared it to the T. b. brucei reference strain. The annotated T.
      evansi genome shows extensive similarity to the reference, with 94.9% of the
      predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi,
      and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or
      greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted
      or not found in this T. evansi strain, suggesting a selective loss of function in
      the absence of the insect life-cycle stage. Surprisingly, orthologous sequences
      were found in T. evansi for all 978 nuclear CDS predicted to represent the
      mitochondrial proteome in T. brucei, although a small number of these may have
      lost functionality. Consistent with previous results, the F1FO-ATP synthase gamma
      subunit was found to have an A281 deletion, which is involved in generation of a
      mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that
      are absent from the reference genome were identified in supplementary de novo
      assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced
      strain belongs to a dominant group of clonal T. evansi strains with worldwide
      distribution that also includes isolates classified as T. equiperdum. At least
      three other types of T. evansi or T. equiperdum have emerged independently.
      Overall, the elucidation of the T. evansi genome sequence reveals extensive
      similarity of T. brucei and supports the contention that T. evansi should be
      classified as a subspecies of T. brucei. 

PMID- 25568945
TI  - Regulating maf1 expression and its expanding biological functions.

PMID- 25568944
TI  - Macrophage-derived human resistin is induced in multiple helminth infections and
      promotes inflammatory monocytes and increased parasite burden.
AB  - Parasitic helminth infections can be associated with lifelong morbidity such as
      immune-mediated organ failure. A better understanding of the host immune response
      to helminths could provide new avenues to promote parasite clearance and/or
      alleviate infection-associated morbidity. Murine resistin-like molecules (RELM)
      exhibit pleiotropic functions following helminth infection including modulating
      the host immune response; however, the relevance of human RELM proteins in
      helminth infection is unknown. To examine the function of human resistin
      (hResistin), we utilized transgenic mice expressing the human resistin gene
      (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis
      (Nb), hResistin expression was significantly upregulated in infected tissue.
      Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb
      induced inflammation characterized by weight loss and increased infiltration of
      inflammatory monocytes in the lung, along with elevated Nb egg burdens and
      delayed parasite expulsion. Genome-wide transcriptional profiling of the infected
      tissue revealed that hResistin promoted expression of proinflammatory cytokines
      and genes downstream of toll-like receptor signaling. Moreover, hResistin
      preferentially bound lung monocytes, and exogenous treatment of mice with
      recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine
      expression. In human studies, increased serum resistin was associated with higher
      parasite load in individuals infected with soil-transmitted helminths or filarial
      nematode Wuchereria bancrofti, and was positively correlated with proinflammatory
      cytokines. Together, these studies identify human resistin as a detrimental
      factor induced by multiple helminth infections, where it promotes proinflammatory
      cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory
      cytokine immune axis may provide new diagnostic or treatment strategies for
      helminth infection and associated immune-mediated pathology. 

PMID- 25568946
TI  - Preferential use of central metabolism in vivo reveals a nutritional basis for
      polymicrobial infection.
AB  - The human genitourinary tract is a common anatomical niche for polymicrobial
      infection and a leading site for the development of bacteremia and sepsis. Most
      uncomplicated, community-acquired urinary tract infections (UTI) are caused by
      Escherichia coli, while another bacterium, Proteus mirabilis, is more often
      associated with complicated UTI. Here, we report that uropathogenic E. coli and
      P. mirabilis have divergent requirements for specific central pathways in vivo
      despite colonizing and occupying the same host environment. Using mutants of
      specific central metabolism enzymes, we determined glycolysis mutants lacking
      pgi, tpiA, pfkA, or pykA all have fitness defects in vivo for P. mirabilis but do
      not affect colonization of E. coli during UTI. Similarly, the oxidative pentose
      phosphate pathway is required only for P. mirabilis in vivo. In contrast,
      gluconeogenesis is required only for E. coli fitness in vivo. The remarkable
      difference in central pathway utilization between E. coli and P. mirabilis during
      experimental UTI was also observed for TCA cycle mutants in sdhB, fumC, and frdA.
      The distinct in vivo requirements between these pathogens suggest E. coli and P.
      mirabilis are not direct competitors within host urinary tract nutritional niche.
      In support of this, we found that co-infection with E. coli and P. mirabilis wild
      type strains enhanced bacterial colonization and persistence of both pathogens
      during UTI. Our results reveal that complementary utilization of central carbon
      metabolism facilitates polymicrobial disease and suggests microbial activity in
      vivo alters the host urinary tract nutritional niche. 

PMID- 25568948
TI  - Breast arterial calcifications: a systematic review and meta-analysis of their
      determinants and their association with cardiovascular events.
AB  - OBJECTIVE: Breast arterial calcifications (BAC), regularly observed at
      mammography, are medial calcifications and as such an expression of
      arteriosclerosis. Our objective was to evaluate and summarize the available
      evidence on the associations of BAC with cardiovascular risk factors and
      cardiovascular risk. METHODS: A systematic literature review and meta-analysis
      were conducted. Embase and PubMed databases were searched. After critical
      appraisal, odds ratios were extracted from studies of moderate or good quality
      that examined risk factors for BAC or associations of BAC with cardiovascular
      disease. Random effects model meta-analyses were used to calculate pooled odds
      ratios and 95% confidence intervals (95%CIs). RESULTS: BAC prevalence is around
      12.7% among women in breast cancer screening programs. Increasing age (pooled OR
      2.98 [95%CI 2.31-3.85] for every 10 years), diabetes (pooled OR: 1.88 [95%CI 1.36
      2.59]) and parity as opposed to nulliparity (pooled OR 3.43 [95%CI 2.23-5.27])
      are associated with higher BAC prevalence. Smoking is associated with lower BAC
      prevalence (pooled OR 0.48 [95%CI 0.39-0.60]). No associations were found with
      hypertension, obesity or dyslipidemia. Although longitudinal studies (n = 3) were
      scarce, BAC appear to be associated with an increased risk of cardiovascular
      disease events (adjusted hazard ratios for coronary heart disease ranging from
      1.32 [95%CI 1.08-1.60] to 1.44 [95%CI1.02-2.05]). CONCLUSION: BAC appear to be
      associated with an increased risk of cardiovascular disease events, while only
      being associated with some of the known cardiovascular risk factors, illustrating
      that medial arterial calcification might contribute to cardiovascular disease
      through a pathway distinct from the intimal atherosclerotic process.

PMID- 25568949
TI  - Weight loss improves fasting flow-mediated vasodilation in adults: a meta
      analysis of intervention studies.
AB  - BACKGROUND: Obesity is associated with vascular endothelial dysfunction. Effects
      of weight loss on endothelial function are however not clear. Therefore, we
      performed a meta-analysis to quantify effects of weight loss on flow-mediated
      vasodilation (FMD) of the brachial artery, a measurement of endothelial function.
      METHODS: Studies with experimental (RCTs) and quasi-experimental designs
      published before June 2014 were identified by a systematic search. Changes in FMD
      were defined as the difference between measurements before and after the study.
      For RCTs, changes were corrected for those in the no-weight loss control group.
      Summary estimates of weighted mean differences (WMDs) in FMD and 95% confidence
      intervals (CIs) were calculated using random-effect meta-analyses. The impact of
      subject characteristics, type of weight-loss treatment, and dietary composition
      on changes in FMD was also investigated. RESULTS: Four RCTs involving 265
      subjects were included. Weight loss increased FMD vs. control by 3.29% (95% CI:
      0.98-5.59%; P = 0.005; mean weight loss: 8.6 kg). A total of 1517 subjects
      participated in 33 studies with 49 relevant study arms. It was estimated that
      each 10 kg decrease in body weight increased fasting FMD by 1.11% (95% CI: 0.47
      1.76%; P = 0.001). Effects were more pronounced when participants had coexisting
      obesity-related morbidities. Also, effects may be larger when subjects received
      low-fat diets or weight-reduction regimens including exercise therapy or weight
      loss medication. CONCLUSION: Weight loss significantly improves fasting FMD in
      adults, which is a risk marker for cardiovascular disease. Effects may depend on
      subject characteristics, type of weight-loss treatment, and dietary composition.

PMID- 25568950
TI  - Cross-sectional and longitudinal associations between serum bilirubin and
      dyslipidemia in a health screening population.
AB  - OBJECTIVE: To investigate cross-sectional and longitudinal associations between
      serum total bilirubin (TB) and dyslipidemia. METHODS: Odds ratios (ORs) of
      prevalent dyslipidemia for TB were calculated in 2113 men and 1265 women.
      Correlation coefficients between baseline TB as well as the change in TB over 5
      years and baseline log triglycerides, baseline HDL cholesterol and the changes in
      log triglycerides and HDL cholesterol over 5 years were calculated. Hazard ratios
      (HRs) of incident hypertriglyceridemia and hypo-HDL cholesterolemia for TB over 5
      years were calculated in 1324 men and 915 women and 1583 men and 884 women,
      respectively. RESULTS: The ORs of prevalent hypertriglyceridemia and hypo-HDL
      cholesterolemia for each one SD increase in TB were 0.83 (p < 0.001) in men and
      0.71 (p = 0.074) in women and 0.64 (p < 0.001) in men and 0.78 (p = 0.089) in
      women, respectively adjusted for age, smoking, and other confounders. The
      baseline TB was significantly correlated with baseline log triglycerides and HDL
      cholesterol both in men and women while the change in TB was significantly
      correlated with the changes in log triglycerides and HDL cholesterol in men and
      the change in HDL cholesterol in women. The HRs of incident hypertriglyceridemia
      and hypo-HDL cholesterolemia for each one SD increase in TB were 0.99 (p = 0.848)
      in men and 0.74 (p = 0.033) in women and 1.08 (p = 0.345) in men and 0.85 (p =
      0.220) in women, respectively adjusted for age, smoking, and other confounders.
      CONCLUSION: Baseline TB was significantly associated with both prevalent
      hypertriglyceridemia and hypo-HDL cholesterolemia in men and with incident
      hypertriglyceridemia in women.

PMID- 25568947
TI  - Variable frequency of plastid RNA editing among ferns and repeated loss of
      uridine-to-cytidine editing from vascular plants.
AB  - The distinct distribution and abundance of C-to-U and U-to-C RNA editing among
      land plants suggest that these two processes originated and evolve independently,
      but the paucity of information from several key lineages limits our understanding
      of their evolution. To examine the evolutionary diversity of RNA editing among
      ferns, we sequenced the plastid transcriptomes from two early diverging species,
      Ophioglossum californicum and Psilotum nudum. Using a relaxed automated approach
      to minimize false negatives combined with manual inspection to eliminate false
      positives, we identified 297 C-to-U and three U-to-C edit sites in the O.
      californicum plastid transcriptome but only 27 C-to-U and no U-to-C edit sites in
      the P. nudum plastid transcriptome. A broader comparison of editing content with
      the leptosporangiate fern Adiantum capillus-veneris and the hornwort Anthoceros
      formosae uncovered large variance in the abundance of plastid editing, indicating
      that the frequency and type of RNA editing is highly labile in ferns. Edit sites
      that increase protein conservation among species are more abundant and more
      efficiently edited than silent and non-conservative sites, suggesting that
      selection maintains functionally important editing. The absence of U-to-C editing
      from P. nudum plastid transcripts and other vascular plants demonstrates that U
      to-C editing loss is a recurrent phenomenon in vascular plant evolution. 

PMID- 25568951
TI  - Inhibition of xanthine oxidase to prevent statin-induced myalgia and
      rhabdomiolysis.
AB  - Although statins remain the cornerstone of lipid-lowering therapy for reducing
      the burden of atherosclerotic vascular disease, their administration has been
      associated with muscle-related adverse effects, including myalgia and
      rhabdomyolysis. Such adverse events are probably due to reduced antioxidant
      defenses associated with fewer intermediate metabolites in the cholesterol
      synthesis pathway. We hypothesize that the concomitant inhibition of xanthine
      oxidase via coadministration of allopurinol with statins could diminish reactive
      oxygen species (ROS)-related muscle damage, which would have in turn have
      positive effects on both the incidence of muscle-related adverse events and
      cardiovascular outcomes. Accordingly, inhibition of xanthine oxidase has been
      previously shown to be effective for reducing biomarkers of muscle damage
      following exercise in professional athletes. Because of the widespread statin
      utilization and increasing trends in their therapeutic use in atherosclerotic
      vascular diseases, the proposed strategy could have important clinical
      implications for reducing statin-induced myalgia and rhabdomyolysis. 

PMID- 25568952
TI  - Effect of fitness on incident diabetes from statin use in primary prevention.
AB  - OBJECTIVE: To assess the effect of cardiorespiratory fitness on the association
      between the initiation of statin therapy and incident diabetes. PATIENTS AND
      METHODS: In a prospective observational study, we studied 6519 generally healthy
      men and 2334 women with two preventive health examinations from December 15, 1998
      through December 18, 2013 which included measurement of fitness levels, statin
      therapy, risk factors for diabetes, and incident diabetes. RESULTS: 93 cases of
      incident diabetes occurred during an average follow-up of 3.0 years. After
      multivariable adjustment, an increased odds of incident diabetes with statin use
      was observed in those patients with impaired fasting glucose at baseline (odds
      ratio [OR]: 2.15, [95% CI:1.26 to 3.67]), but not among individuals with normal
      glucose levels (OR:1.85, [95% CI: 0.76 to 4.52]). Cardiorespiratory fitness
      attenuated but did not eliminate the increased risk of incident diabetes with
      statin use. CONCLUSION: In a population of relatively healthy patients, statin
      use was not associated with incident diabetes in patients with normal fasting
      glucose at baseline. However, it was associated with incident diabetes in those
      patients with impaired fasting glucose at baseline, though this risk was
      substantially reduced by increasing fitness. In addition, increasing
      cardiorespiratory fitness was inversely associated with incident diabetes whether
      or not a patient was treated with a statin.

PMID- 25568953
TI  - Dosimetry of electromagnetic field exposure of an active armlet and its
      electromagnetic interference to the cardiac pacemakers using adult, child and
      infant models.
AB  - Wearable devices have been popularly used with people from different age groups.
      As a consequence, the concerns of their electromagnetic field (EMF) exposure to
      the human body and their electromagnetic interference (EMI) to the implanted
      medical devices have attracted many studies. The aim of this study was to
      evaluate the human exposure to the EMF of an active radiofrequency identification
      (RFID) armlet as well as its EMI to the cardiac pacemaker (CP). Different human
      models from various age groups were applied to assess the result variability. The
      scalar potential finite element method was utilized in the simulation. Local EMF
      exposure and the exposure to the central nerve system tissues were evaluated
      using different metrics. EMI to the CP was assessed in terms of the conducted
      voltage to the CP. The results from all the models revealed that the studied RFID
      armlet would not produce the EMF exposure exceeding the safety limits. The
      calculated interference voltage was highly dependent on the distance between the
      RFID armlet and the CP (i.e. the physical dimension of the individual model). The
      results proposed to evaluate the appropriateness of the current EMI measurement
      protocol for this kind of devices used by the infants. 

PMID- 25568954
TI  - Mapping the Pareto optimal design space for a functionally deimmunized
      biotherapeutic candidate.
AB  - The immunogenicity of biotherapeutics can bottleneck development pipelines and
      poses a barrier to widespread clinical application. As a result, there is a
      growing need for improved deimmunization technologies. We have recently described
      algorithms that simultaneously optimize proteins for both reduced T cell epitope
      content and high-level function. In silico analysis of this dual objective design
      space reveals that there is no single global optimum with respect to protein
      deimmunization. Instead, mutagenic epitope deletion yields a spectrum of designs
      that exhibit tradeoffs between immunogenic potential and molecular function. The
      leading edge of this design space is the Pareto frontier, i.e. the undominated
      variants for which no other single design exhibits better performance in both
      criteria. Here, the Pareto frontier of a therapeutic enzyme has been designed,
      constructed, and evaluated experimentally. Various measures of protein
      performance were found to map a functional sequence space that correlated well
      with computational predictions. These results represent the first systematic and
      rigorous assessment of the functional penalty that must be paid for pursuing
      progressively more deimmunized biotherapeutic candidates. Given this capacity to
      rapidly assess and design for tradeoffs between protein immunogenicity and
      functionality, these algorithms may prove useful in augmenting, accelerating, and
      de-risking experimental deimmunization efforts. 

PMID- 25568957
TI  - Attachment style dimensions are associated with brain activity in response to
      gaze interaction.
AB  - Aim of the present study was to investigate the time course of brain processes
      involved in the visual perception of different gaze interactions in woman-child
      dyads and the association between attachment dimensions and brain activation
      during the presentation of gaze interactions. The hypothesis was that the woman
      avoidance will produce a greater activation of primary somatosensory and limbic
      areas. The attachment styles dimensions avoidant-related will be associated with
      fronto-limbic brain intensity during the convergence of gaze.
      Electroencephalogram (EEG) data were recorded using a 256-channel HydroCel
      Geodesic Sensor Net in 44 female subjects (age: 24 +/- 2 years). Event-related
      potential (ERP) components and standardized low-resolution electromagnetic
      tomography (sLORETA) were analyzed. Participants were administered the attachment
      style questionnaire before EEG task. A lower P350 latency was found in the fronto
      central montage in response to woman avoidance. sLORETA analysis showed a greater
      intensity of limbic and primary somatosensory areas in response to woman
      avoidance compared to the others gaze interactions. In response to convergence
      gaze, the confidence attachment dimension was negatively correlated with the
      intensities of the right temporal and limbic areas, and the relationships as
      secondary attachment dimension were positively correlated with the intensities of
      the bilateral frontal areas and of the left parietal area.

PMID- 25568956
TI  - Sero-prevalence and cross-reactivity of chikungunya virus specific anti-E2EP3
      antibodies in arbovirus-infected patients.
AB  - Chikungunya virus (CHIKV) and clinically-related arboviruses cause large
      epidemics with serious economic and social impact. As clinical symptoms of CHIKV
      infections are similar to several flavivirus infections, good detection methods
      to identify CHIKV infection are desired for improved treatment and clinical
      management. The strength of anti-E2EP3 antibody responses was explored in a
      longitudinal study on 38 CHIKV-infected patients. We compared their anti-E2EP3
      responses with those of patients infected with non-CHIKV alphaviruses, or
      flaviviruses. E2EP3 cross-reactive samples from patients infected with non-CHIKV
      viruses were further analyzed with an in vitro CHIKV neutralization assay. CHIKV
      specific anti-E2EP3 antibody responses were detected in 72% to 100% of patients.
      Serum samples from patients infected with other non-CHIKV alphaviruses were cross
      reactive to E2EP3. Interestingly, some of these antibodies demonstrated clearly
      in vitro CHIKV neutralizing activity. Contrastingly, serum samples from
      flaviviruses-infected patients showed a low level of cross-reactivity against
      E2EP3. Using CHIKV E2EP3 as a serology marker not only allows early detection of
      CHIKV specific antibodies, but would also allow the differentiation between CHIKV
      infections and flavivirus infections with 93% accuracy, thereby allowing precise
      acute febrile diagnosis and improving clinical management in regions newly
      suffering from CHIKV outbreaks including the Americas. 

PMID- 25568955
TI  - Heterologous aggregates promote de novo prion appearance via more than one
      mechanism.
AB  - Prions are self-perpetuating conformational variants of particular proteins. In
      yeast, prions cause heritable phenotypic traits. Most known yeast prions contain
      a glutamine (Q)/asparagine (N)-rich region in their prion domains. [PSI+], the
      prion form of Sup35, appears de novo at dramatically enhanced rates following
      transient overproduction of Sup35 in the presence of [PIN+], the prion form of
      Rnq1. Here, we establish the temporal de novo appearance of Sup35 aggregates
      during such overexpression in relation to other cellular proteins. Fluorescently
      labeled Sup35 initially forms one or a few dots when overexpressed in [PIN+]
      cells. One of the dots is perivacuolar, colocalizes with the aggregated Rnq1 dot
      and grows into peripheral rings/lines, some of which also colocalize with Rnq1.
      Sup35 dots that are not near the vacuole do not always colocalize with Rnq1 and
      disappear by the time rings start to grow. Bimolecular fluorescence
      complementation failed to detect any interaction between Sup35-VN and Rnq1-VC in
      [PSI+][PIN+] cells. In contrast, all Sup35 aggregates, whether newly induced or
      in established [PSI+], completely colocalize with the molecular chaperones
      Hsp104, Sis1, Ssa1 and eukaryotic release factor Sup45. In the absence of [PIN+],
      overexpressed aggregating proteins such as the Q/N-rich Pin4C or the non-Q/N-rich
      Mod5 can also promote the de novo appearance of [PSI+]. Similar to Rnq1,
      overexpressed Pin4C transiently colocalizes with newly appearing Sup35
      aggregates. However, no interaction was detected between Mod5 and Sup35 during
      [PSI+] induction in the absence of [PIN+]. While the colocalization of Sup35 and
      aggregates of Rnq1 or Pin4C are consistent with the model that the heterologous
      aggregates cross-seed the de novo appearance of [PSI+], the lack of interaction
      between Mod5 and Sup35 leaves open the possibility of other mechanisms. We also
      show that Hsp104 is required in the de novo appearance of [PSI+] aggregates in a
      [PIN+]-independent pathway. 

PMID- 25568959
TI  - The BMJ should not take the law into its own hands on competing interests.

PMID- 25568958
TI  - Applied research for better disease prevention and control.

PMID- 25568960
TI  - A vomiting baby.

PMID- 25568961
TI  - Heterointerface engineering of broken-gap InAs/GaSb multilayer structures.
AB  - Broken-gap InAs/GaSb strain balanced multilayer structures were grown by
      molecular beam epitaxy (MBE), and their structural, morphological, and band
      alignment properties were analyzed. Precise shutter sequence during the MBE
      growth process, enable to achieve the strain balanced structure. Cross-sectional
      transmission electron microscopy exhibited sharp heterointerfaces, and the
      lattice line extended from the top GaSb layer to the bottom InAs layer. X-ray
      analysis further confirmed a strain balanced InAs/GaSb multilayer structure. A
      smooth surface morphology with surface roughness of ~0.5 nm was demonstrated. The
      effective barrier height -0.15 eV at the GaSb/InAs heterointerface was determined
      by X-ray photoelectron spectroscopy, and it was further corroborated by
      simulation. These results are important to demonstrate desirable characteristics
      of mixed As/Sb material systems for high-performance and low-power tunnel field
      effect transistor applications. 

PMID- 25568962
TI  - Computational organic chemistry: bridging theory and experiment in establishing
      the mechanisms of chemical reactions.
AB  - Understanding the mechanisms of chemical reactions, especially catalysis, has
      been an important and active area of computational organic chemistry, and close
      collaborations between experimentalists and theorists represent a growing trend.
      This Perspective provides examples of such productive collaborations. The
      understanding of various reaction mechanisms and the insight gained from these
      studies are emphasized. The applications of various experimental techniques in
      elucidation of reaction details as well as the development of various
      computational techniques to meet the demand of emerging synthetic methods, e.g.,
      C-H activation, organocatalysis, and single electron transfer, are presented
      along with some conventional developments of mechanistic aspects. Examples of
      applications are selected to demonstrate the advantages and limitations of these
      techniques. Some challenges in the mechanistic studies and predictions of
      reactions are also analyzed. 

PMID- 25568963
TI  - Study of miniemulsion formulation containing 1-octyl-3-methylimidazolium
      hexafluorophosphate for its application in low-emitting coating products.
AB  - Room temperature ionic liquids (RTILs) are non-volatile organic salts, and few of
      them with low melting point may replace the conventional coalescing agents in
      waterborne coatings, thus preventing volatile organic compounds (VOCs) emission,
      caused by coalescing agents. The formation of waterborne coating containing RTILs
      can be achieved by the encapsulation of RTILs inside latexes via miniemulsion
      polymerization. Achieving a stable miniemulsion is a crucial step for further
      polymerization. In this study, 1-octyl-3-methylimidazolium hexafluorophosphate
      (C8mimPF6) was chosen, and various factors which might affect droplet size and
      its stability, including surfactant type, surfactant concentration, and C8mimPF6
      concentration, were investigated. It was found that the presence of a small
      amount of C8mimPF6 coupled with the surfactant would offer marked effects on the
      droplet size reduction and droplet stability. Such effect may reach its maximum
      from 1 to 5 wt% C8mimPF6. Above the critical concentration, adding more C8mimPF6
      to the oil phase may cause a larger initial droplet size as well as weaken the
      droplet stability. Such observations were consistent with the zeta potential
      measurements for miniemulsions prepared under similar conditions. 

PMID- 25568964
TI  - A North/South collaboration between two national public health institutes--a
      model for global health protection.
AB  - Rapid international spread of emerging infections has increased interest in
      strategic collaborations, as they may be the best way to protect populations.
      Strategic collaborations can build capacity in less-resourced settings. As
      specialised institutions that provide a stable locus of expertise, continuity of
      experience, scientific knowledge, and appropriate human, technical, and financial
      resources, national public health institutes (NPHIs) are well-prepared to tackle
      public health challenges. We describe how a collaboration between the NPHIs of
      England and South Africa built a mutually beneficial professional relationship to
      help implement the WHO International Health Regulations, build capacity for
      health protection, and promote the exchange of information, advice, and
      expertise. We illustrate how this can be achieved in a mutually beneficial way. 

PMID- 25568965
TI  - Electrocatalytic amplification of nanoparticle collisions at electrodes modified
      with polyelectrolyte multilayer films.
AB  - We report electrochemical catalytic amplification of individual collisions
      between ~57 nm diameter Pt nanoparticles (Pt NPs) and 12.5 MUm diameter Au
      ultramicroelectrodes modified with passivating, electrostatically assembled
      polyelectrolyte multilayer (PEM) films prepared by the layer-by-layer deposition
      method. Two key findings are reported. First, despite the thicknesses of the
      insulating PEM films, which range up to 5 nm, electrons are able to tunnel from
      the Pt NPs to the electrode resulting in electrocatalytic N2H4 oxidation at the
      PEM film-solution interface. These single-particle measurements are in accord
      with prior reports showing that the electrochemical activity of passive PEM films
      can be reactivated by adsorption of metallic NPs. Second, it is possible to
      control the frequency of the collisions by manipulating the net electrostatic
      charge present on the outer surface of the PEM thin film. These results, which
      demonstrate that chemistry can be used to control electrocatalytic amplification,
      set the stage for future sensing applications. 

PMID- 25568966
TI  - Two or three doses of human papillomavirus vaccine?

PMID- 25568968
TI  - Cognitive differences in schizophrenia on long-term treatments with clozapine,
      risperidone and typical antipsychotics.
AB  - Cognitive deficits are a core feature of schizophrenia. There is ongoing debate
      on whether cognition is affected by antipsychotic drugs (APDs). This study
      examined the effect of long-term treatment with APDs on cognition in
      schizophrenia. Cognitive function was assessed in 418 patients with schizophrenia
      on long-term treatment with APDs (215 on clozapine, 91 on risperidone and 112 on
      typical APDs) and 159 healthy controls using the Repeatable Battery for the
      Assessment of Neuropsychological Status (RBANS). Schizophrenia symptomatology was
      assessed using the Positive and Negative Syndrome Scale (PANSS). We found that
      cognitive test scores were significantly lower in all patients compared with the
      healthy controls on almost all of the total and subscores of RBANS (all P<0.001),
      except for the visuospatial/constructional index. Individuals taking clozapine
      showed worse immediate and delayed memory performance than those taking typical
      APDs (all P<0.01). Moreover, individuals taking clozapine showed better language
      performance than those taking risperidone (P<0.01). Immediate memory and delayed
      memory were modestly correlated with the types of APDs and the PANSS negative
      scores. Our results show that individuals taking clozapine performed worse in
      immediate and delayed memory than those taking typical APDs, but exemplified
      better language performance than those taking risperidone. 

PMID- 25568969
TI  - The role of adolescent nutrition and physical activity in the prediction of
      verbal intelligence during early adulthood: a genetically informed analysis of
      twin pairs.
AB  - A large body of research has revealed that nutrition and physical activity
      influence brain functioning at various stages of the life course. Nevertheless,
      very few studies have explored whether diet and exercise influence verbal
      intelligence as youth transition from adolescence into young adulthood. Even
      fewer studies have explored the link between these health behaviors and verbal
      intelligence while accounting for genetic and environmental factors that are
      shared between siblings. Employing data from the National Longitudinal Study of
      Adolescent Health, the current study uses a sample of same-sex twin pairs to test
      whether youth who engage in poorer fitness and nutritional practices are
      significantly more likely to exhibit reduced verbal intelligence during young
      adulthood. The results suggests that, independent of the effects of genetic and
      shared environmental factors, a number of nutritional and exercise factors during
      adolescence influence verbal intelligence during adulthood. Limitations are noted
      and suggestions for future research are outlined. 

PMID- 25568967
TI  - Th1-biased immunomodulation and therapeutic potential of Artemisia annua in
      murine visceral leishmaniasis.
AB  - BACKGROUND: In the absence of vaccines and limitations of currently available
      chemotherapy, development of safe and efficacious drugs is urgently needed for
      visceral leishmaniasis (VL) that is fatal, if left untreated. Earlier we reported
      in vitro apoptotic antileishmanial activity of n-hexane fractions of Artemisia
      annua leaves (AAL) and seeds (AAS) against Leishmania donovani. In the present
      study, we investigated the immunostimulatory and therapeutic efficacy of AAL and
      AAS. METHODOLOGY/PRINCIPAL FINDINGS: Ten-weeks post infection, BALB/c mice were
      orally administered AAL and AAS for ten consecutive days. Significant reduction
      in hepatic (86.67% and 89.12%) and splenic (95.45% and 95.84%) parasite burden
      with decrease in spleen weight was observed. AAL and AAS treated mice induced the
      strongest DTH response, as well as three-fold decrease in IgG1 and two-fold
      increase in IgG2a levels, as compared to infected controls. Cytometric bead array
      further affirmed the elicitation of Th1 immune response as indicated by increased
      levels of IFN-gamma, and low levels of Th2 cytokines (IL-4 and IL-10) in serum as
      well as in culture supernatant of lymphocytes from treated mice.
      Lymphoproliferative response, IFN-gamma producing CD4+ and CD8+ T lymphocytes and
      nitrite levels were significantly enhanced upon antigen recall in vitro. The co
      expression of CD80 and CD86 on macrophages was significantly augmented. CD8+ T
      cells exhibited CD62Llow and CD44hi phenotype, signifying induction of
      immunological memory in AAL and AAS treated groups. Serum enzyme markers were in
      the normal range indicating inertness against nephro- and hepato-toxicity.
      CONCLUSIONS/SIGNIFICANCE: Our results establish the two-prong antileishmanial
      efficacy of AAL and AAS for cure against L. donovani that is dependent on both
      the direct leishmanicidal action as well as switching-on of Th1-biased protective
      cell-mediated immunity with generation of memory. AAL and AAS could represent
      adjunct therapies for the treatment of leishmaniasis, either alone or in
      combination with other antileishmanial agents.

PMID- 25568970
TI  - Hyperlipidemia and statins affect neurological outcome in lumbar spine injury.
AB  - The disabling pathophysiologic effects of lipid and neuroprotective effects of
      statins have recently been demonstrated for acute spinal cord injuries in animal
      models. This large scale population-based study aimed to investigate the effect
      hyperlipidemia and the use of statins in patients with lumbar spine injury. The
      National Health Insurance Research Database of Taiwan was used to identify
      patients with lumbar spine injury. A total of 2844 patients were grouped into
      three: no hyperlipidemia, hyperlipidemia using low-dose of statins (<=90 of the
      defined daily dosage (DDD)), and severe hyperlipidemia using high-dose of statins
      (>90 DDD). A Cox multiple regression model was used to compare the incidence
      rates of disability among the three groups. The results showed that patients with
      hyperlipidemia appeared a higher risk of permanent disability (adjusted HR =
      1.38, p = 0.28). In subgroup analysis, patients with severe hyperlipidemia had a
      higher risk of disability (adjusted HR = 3.1, p < 0.004), whereas hyperlipidemia
      using low-dose statins had a similar risk of permanently disability (adjusted HR
      = 0.83, p = 0.661). Hyperlipidemia adversely affected the neurological outcomes
      of lumbar spinal injury. Statins may have the potential to reverse this higher
      risk of disability. However, this beneficiary effect of statins only existed in
      patients using a lower dose (<=90 DDD). 

PMID- 25568971
TI  - Empowering sedentary adults to reduce sedentary behavior and increase physical
      activity levels and energy expenditure: a pilot study.
AB  - OBJECTIVE: The purpose of this study was to assess the effectiveness of a 4-week
      intervention in which an online personal activity monitor (Gruve-TechnologiesTM)
      was used to reduce sedentary behavior among sedentary adults. METHOD: Eighteen,
      sedentary adult volunteers (12 men, six women, mean age 29 +/- 4.0 years) were
      recruited to participate in the study. Time spent in sedentary activities and
      light-, moderate-, and vigorous-intensity physical activity and energy
      expenditure were assessed during waking hours using the monitor and the 7-day
      SLIPA Log at both baseline and post-intervention. RESULTS: A significant decrease
      of 33% (3.1 h/day; p < 0.001) was found between the time spent in sedentary
      activities measured at baseline (9.4 +/- 1.1 h/day) and at the end of the 4-week
      intervention (6.3 +/- 0.8 h/day). Consequent to the changes in sedentary time,
      significant increases were found in the amount of time spent in light- (45% (2.6
      h/day), p < 0.001), moderate- (33% (1 h/day) p < 0.001), vigorous-intensity
      physical activity (39% (0.16 h/day), p < 0.001), and energy expenditure (47%
      (216.7 kcal/day), p < 0.001). CONCLUSION: This monitor contributes to a
      meaningful reduction in time spent in sedentary activities and has a large effect
      on energy expenditure and physical activity patterns.

PMID- 25568972
TI  - Brand cigarillos--a cheap and less harmful alternative to cigarettes? Particulate
      matter emissions suggest otherwise.
AB  - BACKGROUND: Environmental tobacco smoke (ETS)-associated particulate matter (PM)
      constitutes a considerable health risk for passive smokers. It ought to be
      assessed separately from the other known toxic compounds of tobacco smoke. Brand
      specific differences between cigarettes and particularly between cigarettes and
      favorably taxed cigarillos, are of public interest and therefore worth being
      investigated. METHODS: An automatic environmental tobacco smoke emitter (AETSE)
      was developed to generate cigarette and cigarillo smoke in a reliable and
      reproducible way. John Player Special (JPS) Red cigarettes, JPS filter cigarillos
      and 3R4F standard research cigarettes were smoked automatically in a 2.88 m3
      glass chamber according to a standardized protocol until 5 cm from the top were
      burned down. RESULTS: Mean concentrations (Cmean) and area of the curve (AUC) of
      PM2.5 were measured and compared. Cmean PM2.5 were found to be 804 ug/m3 for 3R4F
      reference cigarettes, 1633 ug/m3 for JPS cigarettes, and 1059 ug/m3 for JPS
      filter cigarillos. AUC PM2.5-values are 433,873 ug/m3*s for 3R4F reference
      cigarettes, 534,267 ug/m3*s for JPS Red cigarettes and 782,850 ug/m3*s for JPS
      filter cigarillos. CONCLUSION: Potential brand-specific differences of ETS
      associated PM emissions among brands of cigarettes, and between cigarettes and
      cigarillos of the same brand and size should be investigated and published.
      Information about relative PM-emissions should be printed on the package.

PMID- 25568974
TI  - Critical state of NHS could worsen, leading economist warns.

PMID- 25568973
TI  - Association between temperature change and outpatient visits for respiratory
      tract infections among children in Guangzhou, China.
AB  - The current study examined the association between temperature change and
      clinical visits for childhood respiratory tract infections (RTIs) in Guangzhou,
      China. Outpatient records of clinical visits for pediatric RTIs, which occurred
      from 1 January 2012 to 31 December 2013, were collected from Guangzhou Women and
      Children's Hospital. Records for meteorological variables during the same period
      were obtained from the Guangzhou Meteorological Bureau. Temperature change was
      defined as the difference between the mean temperatures on two consecutive days.
      A distributed lag non-linear model (DLNM) was used to examine the impact of
      temperature change on pediatric outpatient visits for RTIs. A large temperature
      decrease was associated with a significant risk for an RTI, with the effect
      lasting for ~10 days. The maximum effect of a temperature drop (-8.8  degrees C)
      was reached at lag 2~3 days. Children aged 0-2 years, and especially those aged
      <1 year, were particularly vulnerable to the effects of temperature drop. An
      extreme temperature decrease affected the number of patient visits for both upper
      respiratory tract infections (URTIs) and lower respiratory tract infections
      (LRTIs). A temperature change between consecutive days, and particularly an
      extreme temperature decrease, was significantly associated with increased
      pediatric outpatient visits for RTIs in Guangzhou. 

PMID- 25568976
TI  - Characterization of 27 mycotoxin binders and the relation with in vitro
      zearalenone adsorption at a single concentration.
AB  - The aim of this study was to characterize 27 feed additives marketed as mycotoxin
      binders and to screen them for their in vitro zearalenone (ZEN) adsorption.
      Firstly, 27 mycotoxin binders, commercially available in Belgium and The
      Netherlands, were selected and characterized. Characterization was comprised of X
      ray diffraction (XRD) profiling of the mineral content and d-spacing,
      determination of the cation exchange capacity (CEC) and the exchangeable base
      cations, acidity, mineral fraction, relative humidity (RH) and swelling volume.
      Secondly, an in vitro screening experiment was performed to evaluate the
      adsorption of a single concentration of ZEN in a ZEN:binder ratio of 1:20,000.
      The free concentration of ZEN was measured after 4 h of incubation with each of
      the 27 mycotoxin binders at a pH of 2.5, 6.5 and 8.0. A significant correlation
      between the free concentration of ZEN and both the d-spacing and mineral fraction
      of the mycotoxin binders was seen at the three pH levels. A low free
      concentration of ZEN was demonstrated using binders containing mixed-layered
      smectites and binders containing humic acids. 

PMID- 25568977
TI  - Plectasin, first animal toxin-like fungal defensin blocking potassium channels
      through recognizing channel pore region.
AB  - The potassium channels were recently found to be inhibited by animal toxin-like
      human beta-defensin 2 (hBD2), the first defensin blocker of potassium channels.
      Whether there are other defensin blockers from different organisms remains an
      open question. Here, we reported the potassium channel-blocking plectasin, the
      first defensin blocker from a fungus. Based on the similar cysteine-stabilized
      alpha-beta (CSalphabeta) structure between plectasin and scorpion toxins acting
      on potassium channels, we found that plectasin could dose-dependently block Kv1.3
      channel currents through electrophysiological experiments. Besides Kv1.3 channel,
      plectasin could less inhibit Kv1.1, Kv1.2, IKCa, SKCa3, hERG and KCNQ channels at
      the concentration of 1 MUMU. Using mutagenesis and channel activation
      experiments, we found that outer pore region of Kv1.3 channel was the binding
      site of plectasin, which is similar to the interacting site of Kv1.3 channel
      recognized by animal toxin blockers. Together, these findings not only highlight
      the novel function of plectasin as a potassium channel inhibitor, but also imply
      that defensins from different organisms functionally evolve to be a novel kind of
      potassium channel inhibitors. 

PMID- 25568978
TI  - Preparation of squid skin collagen hydrolysate as an antihyaluronidase,
      antityrosinase, and antioxidant agent.
AB  - A collagen was isolated from squid skin, a processing waste product. The
      biofunctional activities of enzymatic squid skin collagen hydrolysates were
      determined to produce a value-added material. Five low-molecular-mass hydrolysate
      fractions, F1 (>30 kD), F2 (10-30 kD), F3 (3-10 kD), F4 (1-3 kD), and F5 (<1 kD),
      were manufactured from its enzymatic hydrolysate by ultrafiltration. Fraction F3
      had the strongest antihyaluronidase inhibitory activity. Gly, Val, and Pro were
      major amino acids in F3, while Met, Tyr, and His were minor ones. The molecular
      mass of F3 was in the range of 3.4 to 10 kD. F3 exhibited copper chelating
      ability in a concentration-dependent manner. The ferrous chelating ability of F3
      was almost 50% at 200 ug/mL. F3 also inhibited tyrosinase activity by 39.65% at 1
      mg/mL. Furthermore, F3 had stronger hydroxyl radical scavenging activity (IC50 =
      149.94 ug/mL) than ascorbic acid (IC50 = 212.94 ug/mL). Therefore, the squid
      collagen hydrolysate can be utilized as a nutraceutical or cosmeceutical agent.

PMID- 25568980
TI  - Young Age as a Predictor of Poor Road Safety Practices of Commercial
      Motorcyclists in Oyo State, Nigeria.
AB  - OBJECTIVE: This study examined the association between young age and poor road
      safety practices of commercial motorcyclists in Oyo state, Nigeria. METHODS: A
      cross-sectional study of 371 commercial motorcyclists selected via a multistage
      sampling technique was conducted. Information on sociodemographic characteristics
      and road safety practices (possession of a valid license, helmet use, number of
      passengers carried per trip, and compliance with 10 selected traffic signs) was
      obtained with the aid of an interviewer-administered questionnaire. Individual
      road safety practice items were scored and a total score was obtained giving
      minimum and maximum obtainable scores of 0 and 35. Respondents with scores <=
      17.5 (i.e., less than or equal to half of the maximum obtainable score of 35)
      were categorized as having poor road safety practices. Descriptive statistics,
      chi-square, and multiple logistic regression tests were conducted. Selected
      sociodemographic and occupation-related factors were controlled for in the
      logistic regression analysis. RESULTS: All respondents were male, 80.1% had been
      riding for commercial purposes for less than 5 years, and 73.0% had other jobs in
      addition to commercial riding. Road safety practices were generally poor; that
      is, 84.4% of commercial riders were categorized as having poor road safety
      practices. Almost all (98.6%) respondents aged < 25 years compared to 84.3% of
      those aged 25 to <35 years and 76.8% of those >=35 years had poor road safety
      practices. This difference was statistically significant. Following logistic
      regression, younger age (<25 years) remained predictive of poor road safety
      practices. Motorcyclists aged < 25 years had about 16 times higher odds of having
      poor road safety practices compared to those aged 35 years and more (odds ratio =
      15.72, 95% confidence interval, 1.82-135.91). CONCLUSION: Most studies conduct
      only bivariate analysis to test the association between age and road practices of
      commercial motorcyclists; however, we investigated the influence of potential
      confounding variables using multivariate analysis. Our findings confirmed young
      age as a predictor of poor road safety practices among our sample of commercial
      motorcyclists and emphasizes the need for road safety programs to target this
      category of riders. The current minimum age for obtaining a rider's license in
      Nigeria is 18 years; our findings suggest that it might be beneficial to increase
      the age at which riders in our study area can obtain a commercial rider's license
      to above 25 years.

PMID- 25568979
TI  - How to match the optimal currently available inhaler device to an individual
      child with asthma or recurrent wheeze.
AB  - Inhaled medications are the cornerstone of treatment in early childhood wheezing
      and paediatric asthma. A match between patient and device and a correct
      inhalation technique are crucial for good asthma control. The aim of this paper
      is to propose an inhaler strategy that will facilitate an inhaler choice most
      likely to benefit different groups of children. The main focus will be on
      pressurised metered dose inhalers and dry powder inhalers. In this paper we will
      discuss (1) practical difficulties with the devices and with inhaled therapy and
      (2) the optimal location for deposition of medicines in the lungs, and (3) we
      will propose a practical and easy way to make the best match between the inhaler
      device and the individual patient. We hope that this paper will contribute to an
      increased likelihood of treatment success and improved adherence to therapy. 

PMID- 25568981
TI  - Single induction dose of etomidate versus other induction agents for endotracheal
      intubation in critically ill patients.
AB  - BACKGROUND: The use of etomidate for emergency airway interventions in critically
      ill patients is very common. In one large registry trial, etomidate was the most
      commonly used agent for this indication. Etomidate is known to suppress adrenal
      gland function, but it remains unclear whether or not this adrenal gland
      dysfunction affects mortality. OBJECTIVES: The primary objective was to assess,
      in populations of critically ill patients, whether a single induction dose of
      etomidate for emergency airway intervention affects mortality.The secondary
      objectives were to address, in populations of critically ill patients, whether a
      single induction dose of etomidate for emergency airway intervention affects
      adrenal gland function, organ dysfunction, or health services utilization (as
      measured by intensive care unit (ICU) length of stay (LOS), duration of
      mechanical ventilation, or vasopressor requirements).We repeated analyses within
      subgroups defined by the aetiologies of critical illness, timing of adrenal gland
      function measurement, and the type of comparator drug used. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE;
      CINAHL; EMBASE; LILACS; International Pharmaceutical Abstracts; Web of Science;
      the Database of Abstracts of Reviews of Effects (DARE); and ISI BIOSIS Citation
      index(SM) on 8 February 2013. We reran the searches in August 2014. We will deal
      with any studies of interest when we update the review.We also searched the
      Scopus database of dissertations and conference proceedings and the US Food and
      Drug Administration Database. We handsearched major emergency medicine, critical
      care, and anaesthesiology journals.We handsearched the conference proceedings of
      major emergency medicine, anaesthesia, and critical care conferences from 1990 to
      current, and performed a grey literature search of the following: Current
      Controlled Trials; National Health Service - The National Research Register;
      ClinicalTrials.gov; NEAR website. SELECTION CRITERIA: We included randomized
      controlled trials in patients undergoing emergency endotracheal intubation for
      critical illness, including but not limited to trauma, stroke, myocardial
      infarction, arrhythmia, septic shock, hypovolaemic or haemorrhagic shock, and
      undifferentiated shock states. We included single (bolus) dose etomidate for
      emergency airway intervention compared to any other rapid-acting intravenous
      bolus single-dose induction agent. DATA COLLECTION AND ANALYSIS: Refinement of
      our initial search results by title review, and then by abstract review was
      carried out by three review authors. Full-text review of potential studies was
      based on their adherence to our inclusion and exclusion criteria. This was
      decided by three independent review authors. We reported the decisions regarding
      inclusion and exclusion in accordance with the PRISMA statement.Electronic
      database searching yielded 1635 potential titles, and our grey literature search
      yielded an additional 31 potential titles. Duplicate titles were filtered leaving
      1395 titles which underwent review of their titles and abstracts by three review
      authors. Sixty seven titles were judged to be relevant to our review, however
      only eight met our inclusion criteria and seven were included in our analysis.
      MAIN RESULTS: We included eight studies in the review and seven in the meta
      analysis. Of those seven studies, only two were judged to be at low risk of bias.
      Overall, no strong evidence exists that etomidate increases mortality in
      critically ill patients when compared to other bolus dose induction agents (odds
      ratio (OR) 1.17; 95% confidence interval (CI) 0.86 to 1.60, 6 studies, 772
      participants, moderate quality evidence). Due to a large number of participants
      lost to follow-up, we performed a post hoc sensitivity analysis. This gave a
      similar result (OR 1.15; 95% CI 0.86 to 1.53). There was evidence that the use of
      etomidate in critically ill patients was associated with a positive
      adrenocorticotropic hormone (ACTH) stimulation test, and this difference was more
      pronounced at between 4 to 6 hours (OR 19.98; 95% CI 3.95 to 101.11) than after
      12 hours (OR 2.37; 95% CI 1.61 to 3.47) post-dosing. Etomidate's use in
      critically ill patients was associated with a small increase in SOFA score,
      indicating a higher risk of multisystem organ failure (mean difference (MD) 0.70;
      95% CI 0.01 to 1.39, 2 studies, 591 participants, high quality evidence), but
      this difference was not clinically meaningful. Etomidate use did not have an
      effect on ICU LOS (MD 1.70 days; 95% CI -2.00 to 5.40, 4 studies, 621
      participants, moderate quality evidence), hospital LOS (MD 2.41 days; 95% CI 
      7.08 to 11.91, 3 studies, 152 participants, moderate quality evidence), duration
      of mechanical ventilation (MD 2.14 days; 95% CI -1.67 to 5.95, 3 studies, 621
      participants, moderate quality evidence), or duration of vasopressor use (MD 1.00
      day; 95% CI -0.53 to 2.53, 1 study, 469 participants). AUTHORS' CONCLUSIONS:
      Although we have not found conclusive evidence that etomidate increases mortality
      or healthcare resource utilization in critically ill patients, it does seem to
      increase the risk of adrenal gland dysfunction and multi-organ system dysfunction
      by a small amount. The clinical significance of this finding is unknown. This
      evidence is judged to be of moderate quality, owing mainly to significant
      attrition bias in some of the smaller studies, and new research may influence the
      outcomes of our review. The applicability of these data may be limited by the
      fact that 42% of the patients in our review were intubated for "being comatose",
      a population less likely to benefit from the haemodynamic stability inherent in
      etomidate use, and less at risk from its potential negative downstream effects of
      adrenal suppression.

PMID- 25568984
TI  - Biological variation: back to basics.

PMID- 25568982
TI  - Differences in copper bioaccumulation and biological responses in three Mytilus
      species.
AB  - Mytilus species are important organisms in marine systems being highly abundant
      and widely distributed along the coast of Europe and worldwide. They are
      typically used in biological effects studies and have a suite of biological
      effects endpoints that are frequently measured and evaluated for stress effects
      in laboratory experiments and field monitoring programmes. Differences in
      bioaccumulation and biological responses of the three Mytilus species following
      exposure to copper (Cu) were investigated. A laboratory controlled exposure study
      was performed with three genetically confirmed Mytilus species; M.
      galloprovincialis, M. edulis and M. trossulus. Chemical bioaccumulation and
      biomarkers were assessed in all three Mytilus species following a 4 day and a 21
      day exposure to waterborne copper concentrations (0, 10, 100 and 500MUg/L).
      Differences in copper bioaccumulation were measured after both 4 and 21 days,
      which suggests some physiological differences between the species. Furthermore,
      differences in response for some of the biological effects endpoints were also
      found to occur following exposure. These differences were discussed in relation
      to either real physiological differences between the species or merely
      confounding factors relating to the species natural habitat and seasonal cycles.
      Overall the study demonstrated that differences in chemical bioaccumulation and
      biomarker responses between the Mytilus spp. occur with potential consequences
      for mussel exposure studies and biological effects monitoring programmes.
      Consequently, the study highlights the importance of identifying the correct
      species when using Mytilus in biological effects studies. 

PMID- 25568983
TI  - Biological variation - reliable data is essential.

PMID- 25568985
TI  - Enrichment and enumeration of circulating tumor cells by efficient depletion of
      leukocyte fractions.

PMID- 25568986
TI  - Microscopic processes ruling the bioavailability of Zn to roots of Euphorbia
      pithyusa L. pioneer plant.
AB  - Euphorbia pithyusa L. was used in a plant growth-promoting assisted field trial
      experiment. To unravel the microscopic processes at the interface, thin slices of
      E. pithyusa roots were investigated by micro-X-ray fluorescence mapping. Roots
      and rhizosphere materials were examined by X-ray absorption spectroscopy at the
      Zn K-edge, X-ray diffraction, and scanning electron microscopy. Results indicate
      some features common to all the investigated samples. (i) In the rhizosphere of
      E. pithyusa, Zn was found to exist in different phases. (ii) Si and Al are mainly
      concentrated in a rim at the epidermis of the roots. (iii) Zn is mostly stored in
      root epidermis and does not appear to be coordinated to organic molecules but
      mainly occurs in mineral phases such as Zn silicates. We interpreted that roots
      of E. pithyusa significantly promote mineral evolution in the rhizosphere.
      Concomitantly, the plant uses Si and Al extracted by soil minerals to build a
      biomineralization rim, which can capture Zn. This Zn silicate biomineralization
      has relevant implications for phytoremediation techniques and for further
      biotechnology development, which can be better designed and developed after
      specific knowledge of molecular processes ruling mineral evolution and
      biomineralization processes has been gained. 

PMID- 25568987
TI  - Maternal source of false-positive fetal sex chromosome aneuploidy in noninvasive
      prenatal testing.
AB  - BACKGROUND: The intent of noninvasive prenatal testing is to screen for fetal
      aneuploidies. The assumption is that overrepresented and underrepresented
      chromosomes are of fetal origin. However, this is not always the case. CASES: We
      report three cases in which maternal sex chromosome aneuploidy (confirmed by
      karyotype), two cases of which were previously unknown, resulted in false
      positive results. In each, results were positive for fetal aneuploidy, but
      neonatal karyotypes confirmed normal karyotype. CONCLUSION: Noninvasive prenatal
      testing assesses the proportion of chromosomes 21, 18, 13, and sex chromosomes in
      maternal circulation. Intrinsic to the analysis is that the underrepresentations
      and overrepresentations are of fetal origin. We present three cases in which this
      assumption is not valid. We suggest that maternal sex chromosome aneuploidy be
      considered when results suggest fetal sex chromosome aneuploidies.

PMID- 25568988
TI  - Simultaneous endometrial aspiration and sonohysterography for the evaluation of
      endometrial pathology in women aged 50 years and older.
AB  - OBJECTIVE: To evaluate the performance of simultaneous endometrial aspiration at
      the time of sonohysterography for screening postmenopausal women at risk for
      endometrial cancer. METHODS: A retrospective cohort study of women older than 50
      years who underwent saline-infusion sonohysterography for the evaluation of their
      endometrium. On completion of imaging, the remaining intracavitary saline and
      endometrial tissue were aspirated through the saline-infusion sonohysterography
      catheter and submitted for pathologic evaluation. Based on the clinical,
      pathologic, and ultrasonographic results, the patients underwent surgical
      treatment with hysteroscopy, hysterectomy, or clinical observation. Follow-up
      results and outcomes were collected using electronic medical records.
      Sensitivity, specificity, and predictive values of saline-infusion
      sonohysterography, endometrial aspiration, and combined approaches for
      endometrial aspiration and sonohysterography were assessed. RESULTS: Six hundred
      three patients underwent endometrial aspiration at the time of sonohysterography.
      Endometrial tissue was present in 567 (94.0%) and outcome data were available for
      540 (89.5%). In 194 (35.9%) patients, final pathology was obtained by surgical
      intervention. The remaining 346 (64.1%) patients were monitored for at least 6
      months. Thirty patients (5.6%) had cancer or endometrial hyperplasia. A
      sequential model, in which endometrial aspiration was done only for positive
      saline-infusion sonohysterography findings, yielded sensitivity of 86.7% (95%
      confidence interval [CI] 69-96%) and specificity of 100% (95% CI 99-100%) for
      detecting endometrial hyperplasia or cancer (area under the curve 0.93).
      Considering proliferative endometrium as abnormal endometrial aspiration reduced
      specificity to 88.3% (95% CI 85-91%, P<.01) without significant increase in
      sensitivity (100%, 95% CI 88-100%, P=.13). CONCLUSION: The high sensitivity and
      specificity of the sequential endometrial aspiration at the time of
      sonohysterography make this approach a useful and reliable screening algorithm
      for detecting endometrial cancer or hyperplasia in postmenopausal women at risk.
      Endometrial aspiration at the time of sonohysterography should be considered as
      an initial one-stop endometrial evaluation in this population.

PMID- 25568989
TI  - Increased cervical cancer risk associated with screening at longer intervals.
AB  - The 2012 national recommendations for cervical cancer screening will produce a
      lower level of cervical cancer protection than previously afforded by annual
      cytology or 3-year cotesting. After a single negative cotest result, the risk of
      cervical cancer is twice as large at 5 years as it is at 3 years. Modeling
      published since the 2012 guidelines were drafted indicates that extending the
      cotesting screening interval from 3 to 5 years at ages 30-64 years will result in
      an additional 1 woman in 369 compliant with screening receiving a cervical cancer
      diagnosis during her lifetime, and an additional 1 in 1,639 dying of cervical
      cancer. The authors believe that a significant number of patients and providers
      would not choose to accept these additional risks if they understood them,
      despite the recognition of potential harms associated with more intensive
      screening. 

PMID- 25568990
TI  - Intimate partner violence and maternal cigarette smoking before and during
      pregnancy.
AB  - OBJECTIVE: To determine the association of intimate partner violence with
      maternal cigarette smoking before and during pregnancy. METHODS: Data were
      obtained for 196,391 U.S. mothers who delivered live neonates from 2004-2008 and
      completed the Pregnancy Risk Assessment Monitoring System survey 2-9 months
      postpartum. Intimate partner violence was defined as being physically hurt by a
      current or expartner in the year before or during pregnancy. Weighted descriptive
      and multivariate analyses were performed. RESULTS: Compared with nonphysically
      abused women, those who experienced physical abuse were 2.1 times more likely to
      smoke before pregnancy (44.0% compared with 21.0%, P<.001) and 2.6 times more
      likely to smoke during pregnancy (29.6% compared with 11.4%, P<.001). Smoking
      prevalence during pregnancy was highest for abused women who were non-Hispanic
      white (42.3% smoked) and lowest for nonabused college graduates (2.2% smoked).
      Smoking rates more than tripled for college graduates in abusive relationships
      (2.2% compared with 7.1%). After adjusting for potential confounding factors,
      abused women were significantly more likely to smoke during pregnancy than
      nonabused women (adjusted odds ratio 1.95, P<.001, 95% confidence interval 1.80
      2.12). CONCLUSION: Women who experienced intimate partner violence had
      significantly higher rates of smoking before pregnancy and were less likely to
      quit during pregnancy than women who did not experience intimate partner
      violence. The American College of Obstetricians and Gynecologists and the U.S.
      Public Services Task Force recommend routine intimate partner violence screening
      with appropriate interventions to prevent violence against women, optimize
      safety, and improve health. Additional and targeted intimate partner violence
      assessment of women who smoke during pregnancy may prove especially beneficial.

PMID- 25568991
TI  - Costs and benefits of opportunistic salpingectomy as an ovarian cancer prevention
      strategy.
AB  - OBJECTIVE: To conduct a cost-effectiveness analysis of opportunistic
      salpingectomy (elective salpingectomy at hysterectomy or instead of tubal
      ligation). METHODS: A Markov Monte Carlo simulation model estimated the costs and
      benefits of opportunistic salpingectomy in a hypothetical cohort of women
      undergoing hysterectomy for benign gynecologic conditions or surgical
      sterilization. The primary outcome measure was the incremental cost-effectiveness
      ratio. Effectiveness was measured in terms of life expectancy gain. Sensitivity
      analyses accounted for uncertainty around various parameters. Monte Carlo
      simulation estimated the number of ovarian cancer cases associated with each
      strategy in the Canadian population. RESULTS: Salpingectomy with hysterectomy was
      less costly ($11,044.32 +/- $1.56) than hysterectomy alone ($11,206.52 +/-
      $29.81) or with bilateral salpingo-oophorectomy ($12,626.84 +/- $13.11) but more
      effective at 21.12 +/- 0.02 years compared with 21.10 +/- 0.03 and 20.94 +/- 0.03
      years, representing average gains of 1 week and 2 months, respectively. For
      surgical sterilization, salpingectomy was more costly ($9,719.52 +/- $3.74) than
      tubal ligation ($9,339.48 +/- $26.74) but more effective at 22.45 +/- 0.02 years
      compared with 22.43 +/- 0.02 years (average gain of 1 week) with an incremental
      cost-effectiveness ratio of $27,278 per year of life gained. Our results were
      stable over a wide range of costs and risk estimates. Monte Carlo simulation
      predicted that salpingectomy would reduce ovarian cancer risk by 38.1% (95%
      confidence interval [CI] 36.5-41.3%) and 29.2% (95% CI 28.0-31.4%) compared with
      hysterectomy alone or tubal ligation, respectively. CONCLUSION: Salpingectomy
      with hysterectomy for benign conditions will reduce ovarian cancer risk at
      acceptable cost and is a cost-effective alternative to tubal ligation for
      sterilization. Opportunistic salpingectomy should be considered for all women
      undergoing these surgical procedures.

PMID- 25568992
TI  - Fetal sex chromosome testing by maternal plasma DNA sequencing: clinical
      laboratory experience and biology.
AB  - OBJECTIVE: To describe the clinical experience with noninvasive prenatal testing
      for fetal sex chromosomes using sequencing of maternal plasma cell-free DNA in a
      commercial laboratory. METHODS: A noninvasive prenatal testing laboratory data
      set was examined for samples in which fetal sex chromosomes were reported.
      Available clinical outcomes were reviewed. RESULTS: Of 18,161 samples with sex
      chromosome results, no sex chromosome aneuploidy was detected in 98.9% and the
      fetal sex was reported as XY (9,236) or XX (8,721). In 4 of 32 cases in which the
      fetal sex was reportedly discordant between noninvasive prenatal testing and
      karyotype or ultrasonogram, a potential biological reason for the discordance
      exists, including two cases of documented co-twin demise, one case of a maternal
      kidney transplant from a male donor, and one case of fetal ambiguous genitalia.
      In the remaining 204 samples (1.1%), one of four sex chromosome aneuploidies
      (monosomy X, XXX, XXY, or XYY) was detected. The frequency of false positive
      results for sex chromosome aneuploidies is a minimum of 0.26% and a maximum of
      1.05%. All but one of the discordant sex chromosome aneuploidy results involved
      the X chromosome. In two putative false-positive XXX cases, maternal XXX was
      confirmed by karyotype. For the false-positive cases, mean maternal age was
      significantly higher in monosomy X (P<.001) and lower in XXX (P=.008).
      CONCLUSION: Noninvasive prenatal testing results for sex chromosome aneuploidy
      can be confounded by maternal or fetal biological phenomena. When a discordant
      noninvasive prenatal testing result is encountered, resolution requires
      additional maternal history, detailed fetal ultrasonography, and determination of
      fetal and possibly maternal karyotypes.

PMID- 25568993
TI  - Assessment of a full dilatation cesarean delivery simulator.
AB  - OBJECTIVE: To assess a full dilatation cesarean delivery simulator and to
      establish expert consensus on the most effective techniques for safe delivery.
      METHODS: Three delivery scenarios with increasing degrees of difficulty were
      tested. Face and content validity were assessed using visual analog scale (VAS)
      scores on how realistic the simulator was and how useful it would be for
      training, respectively. Construct validity was assessed by comparing success at
      delivery and time taken between senior doctors and junior doctors. Expert opinion
      was sought through a questionnaire. RESULTS: The training scenarios were
      undertaken by 30 doctors working in the specialty of obstetrics and gynecology.
      The number of participants able to deliver and the perceived difficulty they
      experienced correlated with the difficulty level of the three scenarios (success:
      scenario 1, 100% [n=30]; scenario 2, 90% [n=27]; and scenario 3, 62% [n=16]
      P<.05; mean VAS: scenario 1, 29/100; scenario 2, 42/100; and scenario 3, 88/100;
      P<.001). Average time to delivery for each scenario was 45 seconds, 43 seconds,
      and 109 seconds, respectively (P<.001). Overall, 87% found the simulator to be
      realistic (median VAS 58/100, interquartile range 40-74) and 93% thought it would
      be useful as a training device (median VAS 80/100, interquartile range 55-97).
      Questionnaires were received from 47 consultants with an average of 18 years of
      experience. High uterine incision and assistance to push the fetal head up
      transvaginally were the only two techniques reported by more than half of the
      respondents. CONCLUSION: This full dilatation cesarean delivery simulator has
      been validated as a training device; we believe it should be used to develop a
      consensus for accepted techniques.

PMID- 25568994
TI  - Patient concerns about human papillomavirus testing and 5-year intervals in
      routine cervical cancer screening.
AB  - OBJECTIVE: To explore attitudes toward new cervical cancer screening options and
      understand factors associated with those beliefs among women in routine
      gynecologic care. METHODS: We used an interviewer-administered survey of 551
      women aged 36-62 years enrolled in the HPV in Perimenopause Study. Poisson
      regression with robust error variance was used to estimate prevalence ratios and
      95% confidence intervals (CIs) to compare women's preferences for cervical cancer
      screening methods and frequency. RESULTS: A majority of women (55.6%, 95% CI 51.4
      59.8%) were aware that screening recommendations had changed, yet 74.1% (95% CI
      70.3-77.7%) still believed women should be screened annually. If recommended by
      their doctor, 68.4% (95% CI 64.4-72.2%) were willing to extend screening to every
      3 years, but only 25.2% (95% CI 21.9-29.2%) would extend screening to 5 years.
      Most women (60.7%, 95% CI 56.5-65.7%) expressed a strong preference for Pap
      testing, and 41.4% (95% CI 37.4-45.6%) expressed at least moderate concern over
      having a human papillomavirus (HPV) test without a Pap test. A desire for more
      frequent care, higher degree of worry and perceived risk, and abnormal screening
      history were all associated with reduced willingness to accept HPV testing and
      longer screening intervals. CONCLUSION: A majority of routinely screened women
      indicated a willingness to adopt a cervical cancer screening strategy of cytology
      alone or Pap-HPV cotesting every 3 years if recommended by their physician.
      However, they remain concerned about HPV testing and extension of screening
      intervals to once every 5 years. Our results suggest continued reticence to
      accepting newer HPV-based screening algorithms among routinely screened women
      older than age 35 years.

PMID- 25568995
TI  - Risk factors for early-occurring and late-occurring incisional hernias after
      primary laparotomy for ovarian cancer.
AB  - OBJECTIVE: To evaluate a cohort of gynecologic oncology patients to discover risk
      factors for early- and late-occurring incisional hernia after midline incision
      for ovarian cancer. METHODS: We collected retrospective data from patients
      undergoing primary laparotomy for ovarian cancer at the University of Wisconsin
      Hospitals and Clinics from 2001 to 2007. Patient characteristics and potential
      risk factors for hernia formation were noted. Physical examination, abdominal
      computerized assisted tomography scans, or both were used to detect hernias 1
      year after surgery (early hernia) and 2 years after surgery (late hernia).
      RESULTS: There were 265 patients available for the 1-year analysis and 189
      patients for the 2-year analysis. Early and late hernia formation occurred in
      9.8% (95% confidence interval [CI] 6.2-12%) and an additional 7.9% (95% CI 4.1
      12%) of patients, respectively. Using multiple logistic regression, poor
      nutritional status (albumin less than 3 g/dL) and suboptimal cytoreductive
      surgery (1 cm or greater residual tumor) were significantly associated with the
      formation of early incisional hernia after midline incision (P<.001 for both).
      Late hernia formation was associated only with age 65 years or older (P=.01).
      CONCLUSION: The formation of early incisional hernias after midline incision is
      associated with poor nutritional status and suboptimal cytoreductive surgery,
      whereas late hernia formation is associated with advanced age.

PMID- 25568996
TI  - Trends in optimal, suboptimal, and questionably appropriate receipt of antenatal
      corticosteroid prophylaxis.
AB  - OBJECTIVE: To conduct a population-based study to assess rates of optimal,
      suboptimal, and questionably appropriate administration of antenatal
      corticosteroid (betamethasone or dexamethasone) use. METHODS: All live births in
      Nova Scotia, Canada, from 1988 to 2012 were included in the study. Temporal
      trends in optimal (proportion of live births at 24-34 weeks of gestation exposed
      to antenatal corticosteroids between 24 hours and 7 days before delivery),
      suboptimal (proportion of live births at 24-34 weeks of gestation exposed to
      antenatal corticosteroids less than 24 hours or more than 7 days before
      delivery), and questionably appropriate exposure to antenatal corticosteroids
      (proportion of live births 35 weeks of gestation or greater exposed to antenatal
      corticosteroids) were quantified using odds ratios (ORs) and 95% confidence
      intervals (CIs). RESULTS: Among 246,459 live births between 1988 and 2012, 2.5%
      received a partial or a full course of antenatal corticosteroids. The rate of
      antenatal corticosteroid exposure for neonates born between 28 and 32 weeks of
      gestation increased from 39.5% in 1988-1992 to 79.3% in 2008-2012, whereas
      exposure for those born at 33-34 weeks of gestation increased from 14.3 to 49.7%.
      Optimal antenatal corticosteroid receipt increased from 10% in 1988 to 23% in
      2012 (OR 2.7, 95% CI 1.6-4.5), suboptimal administration increased from 7 to 34%
      (OR 6.7, 95% CI 3.9-11.6), and questionably appropriate administration increased
      from 0.2% in 1988 to 1.7% in 2012 (OR 7.5, 95% CI 4.9-11.3). Of the women who
      received antenatal corticosteroids in 2012, 52% delivered at 35 weeks of
      gestation or greater. CONCLUSION: Temporal increases in optimal exposure to
      antenatal corticosteroids have been matched by increases in suboptimal and
      questionably appropriate receipt of antenatal corticosteroids, highlighting the
      need for accurate preterm delivery prognostic models.

PMID- 25568997
TI  - Fetal cardiac axis and congenital heart defects in early gestation.
AB  - OBJECTIVE: To investigate the association between cardiac axis and fetal
      congenital heart defects to demonstrate the potential clinical applicability of
      cardiac axis measurement for detection of congenital heart defect in early
      gestation. METHODS: This case-control study was undertaken in three tertiary
      centers with expertise in fetal imaging in early gestation. Fetal cardiac axis
      was evaluated between 11 0/7 and 14 6/7 weeks of gestation in 197 fetuses with
      confirmed congenital heart defects. A control group was selected by matching each
      fetus with a congenital heart defect with two fetuses in the control group with
      similar crown-rump length (+/- 5 mm) and date of study (+/- 2 months). Cardiac
      axis was measured on the four-chamber view as the angle between the line that
      traces the long axis of the heart and the line that bisects the thorax in an
      anteroposterior direction. RESULTS: In the control group, mean cardiac axis was
      44.5 +/- 7.4 degrees . The cardiac axis did not significantly change in early
      pregnancy. In the congenital heart defect group, 25.9% of fetuses had cardiac
      axis measurements within normal limits. In 74.1%, the cardiac axis was abnormal
      including 110 fetuses in the case group with left deviation (cardiac axis >
      97.5th percentile), 19 fetuses in the case group with right deviation (cardiac
      axis < 2.5th percentile), and 17 fetuses in the case group with nonidentifiable
      cardiac axis. The performance of cardiac axis measurement in detection of major
      congenital heart defect was significantly better than enlarged nuchal
      translucency, tricuspid regurgitation, or reversed A-wave in ductus venosus used
      alone or in combination. CONCLUSION: Abnormal cardiac axis is present in two
      thirds of fetuses with congenital heart defect in early gestation. Adding cardiac
      axis assessment to the nuchal translucency measurement is helpful in defining a
      population at risk for fetal congenital heart defect.

PMID- 25568998
TI  - Subspecialty and gender of obstetrics and gynecology faculty in department-based
      leadership roles.
AB  - OBJECTIVE: To characterize the cohort who may become senior leaders in obstetrics
      and gynecology by examining the gender and subspecialty of faculty in academic
      department administrative and educational leadership roles. METHODS: This is an
      observational study conducted through web sites of U.S. obstetrics and gynecology
      residency programs accredited in 2012-2013. RESULTS: In obstetrics and gynecology
      departmental administrative leadership roles, women comprised 20.4% of chairs,
      36.1% of vice chairs, and 29.6% of division directors. Among educational leaders,
      women comprised 31.9% of fellowship directors, 47.3% of residency directors, and
      66.1% of medical student clerkship directors. Chairs were most likely to be
      maternal-fetal medicine faculty (38.2%) followed by specialists in general
      obstetrics and gynecology (21.8%), reproductive endocrinologists (15.6%), and
      gynecologic oncologists (14.7%). Among chairs, 32.9% are male maternal-fetal
      medicine specialists. Family planning had the highest representation of women
      (80.0%) among division directors, whereas reproductive endocrinology and
      infertility had the lowest (15.8%). The largest proportion of women chairs, vice
      chairs, residency program directors, and medical student clerkship directors were
      specialists in general obstetrics and gynecology. CONCLUSION: Women remained
      underrepresented in the departmental leadership roles of chair, vice chair,
      division director, and fellowship director. Representation of women was closer to
      parity among residency program directors, in which women held just under half of
      positions. Nearly one in three department chairs was a male maternal-fetal
      medicine specialist. Compared with subspecialist leaders, specialist leaders in
      general obstetrics and gynecology were more likely to be women.

PMID- 25568999
TI  - Sleep position, fetal growth restriction, and late-pregnancy stillbirth: the
      Sydney stillbirth study.
AB  - OBJECTIVE: To identify potentially modifiable risk factors for late-pregnancy
      stillbirth. METHODS: This was a population-based matched case-control study of
      pregnant women at 32 weeks of gestation or greater booked into tertiary maternity
      hospitals in metropolitan Sydney between January 2006 and December 2011. The case
      group consisted of women with singleton pregnancies with antepartum fetal death
      in utero. Women in the control group were matched for booking hospital and
      expected delivery date with women in the case group. Data collection was
      performed using a semistructured interview and included validated questionnaires
      for specific risk factors. Adjusted odds ratios (ORs) were calculated for a
      priori-specified risk factors using conditional logistic regression. RESULTS:
      There were 103 women in the case group and 192 women in the control group. Mean
      gestation was 36 weeks. Supine sleeping was reported by 10 of 103 (9.7%) of women
      who experienced late-pregnancy stillbirth and by 4 of 192 (2.1%) of women in the
      control group (adjusted OR 6.26, 95% confidence interval [CI] 1.2-34). Women who
      experienced stillbirth were more likely to: have been followed during pregnancy
      for suspected fetal growth restriction, 11.7% compared with 1.6% (adjusted OR
      5.5, 95% CI 1.36-22.5); not be in paid work, 25.2% compared with 9.4% (adjusted
      OR 2.9, 95% CI 1.1-7.6); and to have not received further education beyond high
      school, 41.7% compared with 25.5% (adjusted OR 1.9, 95% CI 1.1-3.5). None of the
      deaths to women who reported supine sleeping were classified as unexplained.
      CONCLUSION: This study suggests that supine sleep position may be an additional
      risk for late-pregnancy stillbirth in an already compromised fetus. The clinical
      management of suspected fetal growth restriction should be investigated further
      as a means of reducing late stillbirth.

PMID- 25569000
TI  - Time interval between endometrial biopsy and surgical staging for type I
      endometrial cancer: association between tumor characteristics and survival
      outcome.
AB  - OBJECTIVE: To examine whether wait time between endometrial biopsy and surgical
      staging correlates with tumor characteristics and affects survival outcomes in
      patients with type I endometrial cancer. METHODS: A retrospective study was
      conducted to examine patients with grade 1 and 2 endometrioid adenocarcinoma
      diagnosed by preoperative endometrial biopsy who subsequently underwent
      hysterectomy-based surgical staging between 2000 and 2013. Patients who received
      neoadjuvant chemotherapy or hormonal treatment were excluded. Time interval and
      grade change between endometrial biopsy and hysterectomy were correlated to
      demographics and survival outcomes. RESULTS: Median wait time was 57 days (range
      1-177 days) among 435 patients. Upgrading of the tumor to grade 3 in the
      hysterectomy specimen was seen in 4.7% of 321 tumors classified as grade 1 and
      18.4% of 114 tumors classified as grade 2 on the endometrial biopsy,
      respectively. Wait time was not associated with grade change (P>.05). Controlling
      for age, ethnicity, body habitus, medical comorbidities, CA 125 level, and stage,
      multivariable analysis revealed that wait time was not associated with survival
      outcomes (5-year overall survival rates, wait time 1-14, 15-42, 43-84, and 85
      days or more; 62.5%, 93.6%, 95.2%, and 100%, respectively, P>.05); however, grade
      1 to 3 on the hysterectomy specimen remained as an independent prognosticator
      associated with decreased survival (5-year overall survival rates, grade 1 to 3
      compared with grade change 1 to 1, 82.1% compared with 98.5%, P=.01). Among grade
      1 preoperative biopsies, grade 1 to 3 was significantly associated with
      nonobesity (P=.039) and advanced stage (P=.019). CONCLUSION: Wait time for
      surgical staging was not associated with decreased survival outcome in patients
      with type I endometrial cancer.

PMID- 25569001
TI  - Unexpected gynecologic malignancy diagnosed after hysterectomy performed for
      benign indications.
AB  - OBJECTIVE: To define the incidence of unexpected gynecologic malignancies among
      women who underwent hysterectomy for benign indications. METHODS: We conducted a
      data analysis of hysterectomy cases from a quality and safety database maintained
      by the Michigan Surgical Quality Collaborative, a statewide group of hospitals
      that voluntarily reports perioperative outcomes. Cases were abstracted from
      January 1, 2013, through December 8, 2013. Benign preoperative surgical
      indications included pelvic mass, family history of cancer, hyperplasia without
      atypia, prolapse, endometriosis, pelvic pain, abnormal uterine bleeding, or
      leiomyomas. Women with a surgical indication of cancer, cervical dysplasia, or
      hyperplasia with atypia were excluded. RESULTS: During the study period, 7,499
      women underwent a hysterectomy and 85.24% (n = 6,360) were performed for benign
      indications. The incidence of unexpected gynecologic malignancy among
      hysterectomies performed for benign indications was 2.7% (n = 172) and included
      ovarian, peritoneal, and fallopian tube cancer (n = 69 [1.08%]), endometrial
      cancer (n = 65 [1.02%]), uterine sarcoma (n = 14 [0.22%]), metastatic cancer (n =
      13 [0.20%]), and cervical cancer (n = 11 [0.17%]). The most common indications
      for hysterectomy were leiomyomas and abnormal uterine bleeding. There was no
      difference in the mean age (46.86 +/- 10.57 compared with 47.0 +/- 10.76 years, P
      = .96) of women with unexpected sarcoma compared with benign disease. Women with
      unexpected sarcoma were more likely to have a history of venous thromboembolism
      and preoperative blood transfusion, but this did not reach statistical
      significance. CONCLUSION: The 2.7% incidence of unexpected gynecologic malignancy
      includes a 0.22% incidence of uterine sarcoma and 1.02% incidence of endometrial
      cancer. No reliable predictors of uterine sarcoma exist and caution is warranted
      in preoperative planning for hysterectomy.

PMID- 25569002
TI  - Early-pregnancy vitamin D deficiency and risk of preterm birth subtypes.
AB  - OBJECTIVE: To estimate the association between maternal 25-hydroxyvitamin D
      concentrations and risk of preterm birth subtypes. METHODS: We performed a case
      cohort study using data and banked samples from patients at a teaching hospital
      in Pittsburgh, Pennsylvania. Eligible participants were women with a prenatal
      aneuploidy screening serum sample at or before 20 weeks of gestation who
      subsequently delivered a singleton, liveborn neonate. Of the 12,861 eligible
      women, we selected 2,327 at random as well as all remaining preterm birth cases
      for a total of 1,126 cases. Serum 25-hydroxyvitamin D was measured using liquid
      chromatography-tandem mass spectrometry. Multivariable log-binomial regression
      models were used to estimate associations between maternal vitamin D status and
      preterm birth at 37 weeks of gestation (separately by spontaneous or indicated)
      and preterm birth at less than 34 weeks of gestation. RESULTS: The incidence of
      preterm birth at less than 37 weeks of gestation was 8.6% overall and 11.3%,
      8.6%, and 7.3% among mothers with serum 25-hydroxyvitamin D less than 50, 50
      74.9, and 75 nmol/L or greater, respectively (P<.01). After adjustment for
      maternal race and ethnicity, prepregnancy body mass index, season, smoking, and
      other confounders, the risk of preterm birth at less than 37 weeks of gestation
      significantly decreased as 25-hydroxyvitamin D increased to approximately 90
      nmol/L and then plateaued (test of nonlinearity P<.01). Results were similar when
      limiting to cases that were medically indicated or occurred spontaneously and
      cases occurring at less than 34 weeks of gestation. CONCLUSION: Our data support
      a protective association maternal vitamin D sufficiency and preterm birth that
      combined with extant epidemiologic data may provide justification for a
      randomized clinical trial of maternal vitamin D replacement or supplementation to
      prevent preterm birth.

PMID- 25569003
TI  - Three-dimensional computed tomography of pelvic masses in Mayer-Rokitansky-Kuster
      Hauser syndrome.
AB  - BACKGROUND: Mayer-Rokitansky-Kuster-Hauser syndrome is a rare congenital anomaly
      characterized by congenital aplasia or hypoplasia of the uterus and vagina. We
      report a case of Mayer-Rokitansky-Kuster-Hauser syndrome with multiple large
      pelvic masses diagnosed by three-dimensional computed tomography (CT)
      angiography. CASE: A 40-year-old woman with Mayer-Rokitansky-Kuster-Hauser
      syndrome presented with an abdominal mass that had grown for 3 months. Magnetic
      resonance imaging (MRI) confirmed several solid masses, and normal bilateral
      ovaries were detected; three-dimensional CT revealed that these tumors were
      supplied from the right ovarian and uterine arteries, suggesting that they arose
      from the uterus. Accordingly, leiomyoma was suspected. Laparoscopic surgery was
      contraindicated, and the patient therefore underwent laparotomy. The masses were
      resected with the bilateral rudimentary uteri and fallopian tubes, and pathologic
      evaluation confirmed leiomyoma. CONCLUSIONS: Combined MRI and three-dimensional
      CT angiography can accurately evaluate the origin and anatomic properties of
      leiomyomas in patients with Mayer-Rokitansky-Kuster-Hauser syndrome.

PMID- 25569004
TI  - Alpha-fetoprotein as a tool to distinguish amniotic fluid from urine, vaginal
      discharge, and semen.
AB  - OBJECTIVE: To estimate whether alpha-fetoprotein (AFP) can be used to distinguish
      amniotic fluid absorbed in sanitary pads from other similarly absorbed substances
      (semen, urine, and normal vaginal discharge). METHODS: A prospective cohort
      study. Urine and amniotic fluid specimens were collected from 52 pregnant women
      admitted for labor. Semen specimens were collected from 17 men undergoing
      infertility evaluation. Alpha-fetoprotein concentrations were measured directly
      from urine, amniotic fluid, and semen and from pads instilled with samples from
      these specimens. Alpha-fetoprotein concentrations were also measured from pads
      absorbed with normal vaginal discharge collected from 27 pregnant women. RESULTS:
      Alpha-fetoprotein levels in amniotic fluid (245.38 +/- 21.03 ng/mL, n = 52) were
      significantly higher than those measured in maternal urine (0.84 +/- 0.17 ng/mL,
      n = 52, P < .001), or semen (1.52 +/- 0.35 ng/mL, n = 17, P < .001). The same
      trend was seen when AFP was extracted from pads: amniotic fluid levels (19.44 +/-
      1.98 ng/mL, n=52) were significantly higher than those of urine (undetectable,
      n=52), semen (undetectable, n = 17), or normal vaginal discharge (0.53 +/- 0.16
      ng/mL, n = 27, P < .001). Receiver operator characteristic curve analysis
      demonstrated 96.2% sensitivity and 100% specificity for distinguishing the
      presence of amniotic fluid from normal vaginal discharge on sanitary pads (cutoff
      3.88 ng/mL, area under the curve 0.99). CONCLUSION: When the diagnosis of rupture
      of membranes is in doubt, AFP levels can assist in differentiating amniotic fluid
      from other bodily fluids. A method that utilizes sanitary pads and an assay for
      AFP quantification may be an accurate and convenient way to confirm the diagnosis
      of rupture of membranes.

PMID- 25569005
TI  - Buprenorphine and naloxone compared with methadone treatment in pregnancy.
AB  - OBJECTIVE: To compare neonatal abstinence syndrome prevalence and characteristics
      among neonates born to women prescribed buprenorphine and naloxone compared with
      methadone during pregnancy. METHODS: Retrospective cohort analysis of mother
      neonate dyads treated with either buprenorphine and naloxone or methadone during
      pregnancy. Primary neonatal outcomes included diagnosis of neonatal abstinence
      syndrome, neonatal abstinence syndrome peak scores, total amount of morphine used
      to treat neonatal abstinence syndrome (mg), and duration of treatment for
      neonatal abstinence syndrome (days). Secondary outcomes included head
      circumference, birth weight, length, preterm birth, neonatal intensive care unit
      admission, Apgar scores, and overall length of hospitalization. RESULTS: From
      January 1, 2011, to November 30, 2013, we identified 62 mother-neonate dyads, 31
      treated with methadone and 31 treated with buprenorphine and naloxone. Sixteen
      neonates (51.6%) in the methadone group were diagnosed with neonatal abstinence
      syndrome compared with eight (25.1%) in the buprenorphine and naloxone group
      (adjusted odds ratio 2.55, 95% confidence interval [CI] 1.31-4.98, P = .01). The
      buprenorphine and naloxone-exposed neonates had lower peak neonatal abstinence
      syndrome scores (9.0 +/- 4.4 compared with 10.7 +/- 3.7, multivariate-adjusted
      mean difference = -2.77, 95% CI -4.99 to -0.56, P = .02) and shorter overall
      hospitalization (5.6 +/- 5.0 compared with 9.8 +/- 7.4 days, multivariate
      adjusted mean difference = -3.90, 95% CI, -7.13 to -0.67, P = .02). We found no
      other differences in primary or secondary outcomes. CONCLUSION: In a cohort of
      pregnant patients treated with either methadone or buprenorphine and naloxone in
      pregnancy, newborns exposed to maternal buprenorphine and naloxone had less
      frequent neonatal abstinence syndrome. Additionally, neonates exposed to
      buprenorphine and naloxone had shorter overall hospitalization lengths.

PMID- 25569006
TI  - Prophylactic use of negative pressure wound therapy after cesarean delivery.
AB  - OBJECTIVE: To evaluate the economic benefit of prophylactic negative pressure
      wound therapy on a closed laparotomy incision after cesarean delivery in
      comparison with standard postoperative dressing. METHODS: We designed a decision
      analytic model from a third-party payer's perspective to determine the cost
      benefit of prophylactic application of negative pressure wound therapy compared
      with standard postoperative dressing on a closed laparotomy incision after
      cesarean delivery. Our primary outcome measure was the expected value of the cost
      per strategy. Baseline probabilities and cost assumptions were derived from
      published literature. We conducted sensitivity analyses using both deterministic
      and probabilistic models. Cost estimates reflect 2014 U.S. dollars. RESULTS:
      Under our baseline parameters, standard postoperative dressing was the preferred
      strategy. Standard postoperative dressing and prophylactic negative pressure
      wound therapy cost $547 and $804 per strategy, respectively. Sensitivity analyses
      showed that prophylactic negative pressure wound therapy can be cost-beneficial
      if it is priced below $192; standard postoperative dressing is the preferred
      strategy among patients with surgical site infection rate of 14% or less. If
      surgical site infection rates are greater than 14%, prophylactic negative
      pressure wound therapy could be cost-beneficial depending on the degree of
      reduction in surgical site infections. At a surgical site infection rate of 30%,
      the rate must be reduced by 15% for negative pressure wound therapy to become the
      preferred strategy. Monte Carlo simulation of 1,000 patients in 1 million trials
      showed that standard postoperative dressing was the preferred cost-beneficial
      strategy with a frequency of 85%. CONCLUSION: Our cost-benefit analysis provides
      economic evidence suggesting that negative pressure wound therapy should not be
      used on closed laparotomy incisions of patients with low risk of postcesarean
      delivery surgical site infections. However, among patients with a high risk of
      surgical site infections, prophylactic negative pressure wound therapy is
      potentially cost-beneficial.

PMID- 25569008
TI  - Appropriate use of antenatal corticosteroid prophylaxis.

PMID- 25569007
TI  - Factors associated with 30-day hospital readmission after hysterectomy.
AB  - OBJECTIVE: To analyze factors associated with 30-day readmission among women who
      underwent hysterectomy for uterine cancer and benign indications. METHODS: We
      used the National Surgical Quality Improvement Project database to perform a
      cohort study of women who underwent hysterectomy from 2011 to 2012. Patients were
      stratified by surgical indication (uterine cancer or benign indications).
      Multivariable logistic regression models were constructed to determine factors
      associated with 30-day readmission. Model fit statistics were used to evaluate
      the importance of demographic factors, preoperative comorbidities, and
      postoperative complications on readmission. RESULTS: The rate of 30-day
      readmission was 6.1% among 4,725 women with uterine cancer and 3.4% after
      hysterectomy for benign gynecologic disease in 36,471 patients. In a series of
      multivariable models, postoperative complications including wound complications,
      infections, and pulmonary emboli and myocardial infarctions were the factors most
      strongly associated with readmission. Compared with women without a complication,
      complications increased the readmission rate from 2.5 to 20.3% for women with
      uterine cancer and from 1.5 to 15.1% for those without cancer. Among women with
      uterine cancer, postoperative complications explained 34.3% of the variance in
      readmission compared with 5.9% for demographic factors and 2.2% for preoperative
      comorbidities. For patients with benign diseases, complications accounted for
      32.1%, preoperative conditions 1.2%, and demographic factors 2.5% of the variance
      in readmission. CONCLUSION: Efforts to reduce readmission should be directed at
      initiatives to reduce complications and improve the care of women who experience
      a complication.

PMID- 25569009
TI  - Use of primary high-risk human papillomavirus testing for cervical cancer
      screening: interim clinical guidance.
AB  - In 2011, the American Cancer Society, the American Society for Colposcopy and
      Cervical Pathology, and the American Society for Clinical Pathology updated
      screening guidelines for the early detection of cervical cancer and its
      precursors. Recommended screening strategies were cytology or cotesting (cytology
      in combination with high-risk human papillomavirus [hrHPV] testing). These
      guidelines also addressed the use of hrHPV testing alone as a primary screening
      approach, which was not recommended for use at that time. There is now a growing
      body of evidence for screening with primary hrHPV testing, including a
      prospective U.S.-based registration study. Thirteen experts, including
      representatives from the Society of Gynecologic Oncology, the American Society
      for Colposcopy and Cervical Pathology, the American College of Obstetricians and
      Gynecologists, the American Cancer Society, the American Society of
      Cytopathology, the College of American Pathologists, and the American Society for
      Clinical Pathology, convened to provide interim guidance for primary hrHPV
      screening. This guidance panel was specifically triggered by an application to
      the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to
      be labeled for the additional indication of primary cervical cancer screening.
      Guidance was based on literature review and review of data from the FDA
      registration study, supplemented by expert opinion. This document aims to provide
      information for health care providers who are interested in primary hrHPV testing
      and an overview of the potential advantages and disadvantages of this strategy
      for screening as well as to highlight areas in need of further investigation. 

PMID- 25569010
TI  - What is new in exercise in pregnancy? Best articles from the past year.
AB  - This month we focus on current research in exercise in pregnancy. Dr. Blanchette
      discusses four 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- 25569011
TI  - Prophylactic negative pressure wound therapy: we need proof before application.

PMID- 25569012
TI  - Identifying a "range of reasonable options" for cervical cancer screening.

PMID- 25569013
TI  - Discordant embryonic aneuploidy testing and prenatal ultrasonography prompting
      androgen insensitivity syndrome diagnosis.
AB  - BACKGROUND: Multimodal prenatal screening for developmental pathology is
      increasingly common. In this case, definitive prenatal diagnosis of androgen
      insensitivity syndrome was diagnosed after discordant results from karyotypes
      determined by embryonic preimplantation genetic screening and antenatal
      ultrasound results. CASE: A 38-year-old woman, gravida 2 para 0010, undergoing in
      vitro fertilization with preimplantation genetic screening transferred one male
      and one female embryo. An anatomic ultrasonogram revealed two fetuses with female
      genitalia. Cell-free fetal DNA analyzed using noninvasive prenatal screening
      demonstrated Y chromosome material, and amniocentesis confirmed one 46,XX and one
      46,XY fetus. Sequencing of the androgen receptor for the 46,XY fetus identified a
      mutation. CONCLUSION: With increased use, discordance among prenatal testing
      modalities such as preimplantation genetic screening, noninvasive prenatal
      screening, and ultrasonography will become more common requiring expert
      navigation to identify true pathology.

PMID- 25569014
TI  - Female sexual dysfunction: focus on low desire.
AB  - Low or absent sexual desire is the most common sexual dysfunction in women, and
      its prevalence peaks during midlife. Its etiology is complex and may include
      biologic, psychologic, and social elements. Major risk factors for its
      development include poor health status, depression, certain medications,
      dissatisfaction with partner relationship, and history of physical abuse, sexual
      abuse, or both. Diagnosis is based on criteria set by the Diagnostic and
      Statistical Manual of Mental Disorders (5th Edition) and requires that a woman
      experience personal distress. Clinical evaluation should include medical history,
      sexual history, and, sometimes, a physical examination. Laboratory data are of
      limited value, except when warranted by history or physical examination.
      Treatment options include nonpharmacologic interventions such as education,
      office-based counseling, and psychotherapy. Although there are no U.S. Food and
      Drug Administration (FDA)-approved treatments for low desire, pharmacologic
      agents have been used off-label for this purpose. Bupropion is an antidepressant
      that has been shown to improve desire in some women with and without depression.
      Systemic estrogen therapy is not recommended in the absence of vasomotor symptoms
      and is not directly associated with desire. However, vaginal estrogen is useful
      in patients presenting with concomitant vaginal atrophy and dyspareunia.
      Ospemifene is a selective estrogen receptor modulator that can be used as an
      alternative to vaginal estrogen. Exogenous testosterone has demonstrated efficacy
      in treating loss of desire in postmenopausal women. However, patients should be
      counseled that it is not FDA-approved for this purpose and there are limited
      published long-term safety data. Several agents for the treatment of low desire
      are currently in development. Gynecologists are in a unique position to address
      concerns about sexual desire in women. 

PMID- 25569015
TI  - Jacobsen syndrome detected by noninvasive prenatal testing.
AB  - BACKGROUND: Noninvasive prenatal testing has a high detection rate of common
      fetal chromosomal aneuploidies. However, detection of additional chromosome
      abnormalities has not been well described or validated. CASE: We report a case of
      Jacobsen syndrome, a congenital disorder involving deletion of chromosome 11q,
      detected by noninvasive prenatal testing at 14 weeks of gestation and confirmed
      on neonatal testing with array chromosomal genomic hybridization. CONCLUSION:
      Noninvasive prenatal testing should be considered when multiple fetal anomalies
      are present and invasive testing is declined. As the clinical application of
      noninvasive prenatal testing continues to evolve, additional submicroscopic
      chromosomal information may be clinically helpful and should be confirmed with
      diagnostic testing until larger studies help further define the screening
      characteristics of noninvasive prenatal testing.

PMID- 25569016
TI  - Lymphatic mapping and ligation for persistent ascites after surgery for
      gynecologic malignancy.
AB  - BACKGROUND: Ascites after lymphatic dissection, usually amenable to conservative
      management, may require surgery. We describe a technique in the context of
      treatment for gynecologic malignancy to localize and ligate lymphatic leaks.
      CASE: The patient was a 37-year-old woman with recurrent ovarian carcinoma, who
      developed recurrent chylous and lymphatic ascites after secondary cytoreduction
      surgery including lymph node resection in multiple basins. Ascites were
      refractory despite paracenteses, dietary modification, and octreotide therapy.
      Sclerotherapy was unsuccessful. Surgical ligation of the lymphatic leak was
      accomplished with injection of isosulfan blue dye into groin nodes to assist with
      localization. CONCLUSION: Select cases of persistent ascites after surgery for
      gynecologic malignancy will require surgery after conservative measures are
      attempted. Awareness of options for management is important for those caring for
      women with gynecologic cancer.

PMID- 25569018
TI  - Authors' reply to Smith, Forsyth, Coffey and Prendergast, and Soskolne.

PMID- 25569019
TI  - Are individuals with disabilities and their families "resilient"? Deconstructing
      and recasting a well-intended concept.
AB  - This article contributes to existing scholarship related to resilience in
      families with members with disabilities by first using a disability studies
      orientation to "unbound" existing definitions of resilience, then by providing
      empirical illustration of this unbounding. Using family as our unit of analysis,
      we present data from 3 families who navigate successes and challenges related to
      disability. Three themes of honoring relationships, family member expertise, and
      standing in one's power emerged. We suggest that more nuanced understandings of
      resilience, which account for fluid, localized perspectives and encompass
      contradictory meanings and processes (e.g., stress and joy), have implications
      for policy and practice. 

PMID- 25569020
TI  - The role of tonsillectomy in the treatment of pediatric autoimmune
      neuropsychiatric disorders associated with streptococcal infections (PANDAS).
AB  - IMPORTANCE: Pediatric autoimmune neuropsychiatric disorders associated with
      streptococcal infections (PANDAS) in children describes neuropsychiatric symptom
      exacerbations that relate temporally to streptococcal infections. Recent case
      reports suggest tonsillectomy may effectively reduce these symptoms; however, no
      consensus treatment guidelines exist. This study examines whether tonsillectomy
      improves neuropsychiatric symptoms in children with PANDAS who have incomplete
      response to antibiotic therapy. OBSERVATIONS: Ten patients met strict diagnostic
      criteria for PANDAS. Comparisons were made between parental reports of symptom
      severity at diagnosis, after antibiotic treatment (in 10 patients), and after
      tonsillectomy (in 9). From a baseline severity score of 10, antibiotics alone
      improved symptoms to a median (interquartile range [IQR]) score of 8 (6.5-10.0)
      (P = .03). Nine children who subsequently underwent tonsillectomy reported
      symptom improvement in comparison with treatment with antibiotics alone,
      including those with no response to antibiotics. Symptom severity improved at all
      periods after tonsillectomy compared with antibiotics alone. The median score
      [IQR] 3 months postoperatively was 3 (0.0-6.5) (P = .01); 6 months
      postoperatively, 3 (0.0-5.0) (P = .02); 1 year postoperatively, 3 (0.0-5.0) (P =
      .02); and 3 years postoperatively, 0.5 (0.0-2.3) (P = .03). Four of the 9 had
      complete resolution after tonsillectomy. CONCLUSIONS AND RELEVANCE: This PANDAS
      cohort whose neuropsychiatric symptoms did not respond sufficiently to
      antibiotics may have gained benefit from tonsillectomy.

PMID- 25569021
TI  - A Combined Experimental and Computational Study on the Stability of Nanofluids
      Containing Metal Organic Frameworks.
AB  - Computational studies on nanofluids composed of metal organic frameworks were
      performed using molecular modeling techniques. Grand Canonical Monte Carlo
      simulations were used to study the adsorption behavior of 1,1,1,3,3
      pentafluoropropane (R-245fa) in a MIL-101 metal organic frameworks at various
      temperatures. To understand the stability of the nanofluid composed of MIL-101
      particles, we performed molecular dynamics simulations to compute potentials of
      mean force between hypothetical MIL-101 fragments terminated with two different
      kinds of modulators in R-245fa and water. Our computed potentials of mean force
      results indicate that the metal organic frameworks particles tend to disperse
      better in water than in R-245fa. The reasons for this difference in dispersion
      were analyzed and are discussed in the paper. Our results agree with experimental
      results indicating that the potential models employed and modeling approaches
      provide good descriptions of molecular interactions and the reliabilities. 

PMID- 25569022
TI  - Rhodium-catalyzed C-H activation of phenacyl ammonium salts assisted by an
      oxidizing C-N bond: a combination of experimental and theoretical studies.
AB  - Rh(III)-catalyzed C-H activation assisted by an oxidizing directing group has
      evolved to a mild and redox-economic strategy for the construction of
      heterocycles. Despite the success, these coupling systems are currently limited
      to cleavage of an oxidizing N-O or N-N bond. Cleavage of an oxidizing C-N bond,
      which allows for complementary carbocycle synthesis, is unprecedented. In this
      article, alpha-ammonium acetophenones with an oxidizing C-N bond have been
      designed as substrates for Rh(III)-catalyzed C-H activation under redox-neutral
      conditions. The coupling with alpha-diazo esters afforded benzocyclopentanones,
      and the coupling with unactivated alkenes such as styrenes and aliphatic olefins
      gave ortho-olefinated acetophenoes. In both systems the reactions proceeded with
      a broad scope, high efficiency, and functional group tolerance. Moreover,
      efficient one-pot coupling of diazo esters has been realized starting from alpha
      bromoacetophenones and triethylamine. The reaction mechanism for the coupling
      with diazo esters has been studied by a combination of experimental and
      theoretical methods. In particular, three distinct mechanistic pathways have been
      scrutinized by DFT studies, which revealed that the C-H activation occurs via a C
      bound enolate-assisted concerted metalation-deprotonation mechanism and is rate
      limiting. In subsequent C-C formation steps, the lowest energy pathway involves
      two rhodium carbene species as key intermediates. 

PMID- 25569023
TI  - On the maturation of megakaryocytes: a review with original observations on human
      in vivo cells emphasizing morphology and ultrastructure.
AB  - Megakaryocytes engage in the synthesis of a variety of molecular and
      macromolecular constituents to build-up characteristic megakaryocyte structure
      and form proplatelets in a series of cells from megakaryocyte precursors to the
      fully matured cell. The process is illustrated in this review by light microscope
      morphology and transmission electron microscopy, which emphasizes new findings in
      human in vivo megakaryocytes, thereby making a contrast with the abundant
      literature on megakaryocytes from experimental animal and human in vitro
      material. Four stages are identified and described, based on the development of
      characteristic structures including alpha-granules, dense granules (dense-core
      granules), the demarcation membrane system (DMS), and proplatelets. The mechanism
      of DMS development is discussed, in terms of hypotheses suggesting origin from
      the plasma membrane, and contributions of membrane from the Golgi apparatus and
      endoplasmic reticulum. The formation of the marginal zone is also discussed,
      which is suggested to result from a circumscription of the peripheral organelle
      free cytoplasmic fringe by peripheral circular cytoskeletal elements such as
      cytoplasmic actin and microtubules. 

PMID- 25569024
TI  - Molecular characterization of carbapenemase production among gram-negative
      bacteria in saudi arabia.
AB  - We characterized the molecular basis of carbapenemase production in carbapenem
      resistant Gram-negative bacteria isolated from hospitalized patients from Saudi
      Arabia in the year 2012. Isolates were collected from across the Kingdom and
      phenotypically tested for carbapenemase production. Polymerase chain reaction
      detection of carbapenemase genes was also performed. Our results indicate that in
      Saudi Arabia, OXA-48 and NDM-1 are the dominant carbapenemases among
      Enterobacteriaceae with low prevalence of VIM. The latter is the most prevalent
      metallo-beta-lactamase in Pseudomonas aeruginosa, whereas oxacillinases, OXA-23
      in particular, are the dominant carbapenemases in Acinetobacter baumannii. No KPC
      or IMP genes were detected. Our study is the first report of OXA-48, NDM-1, and
      VIM-4 enzymes in Enterobacter from the Kingdom. Also it is the first report of
      OXA-72 and NDM-1 in A. baumannii in Saudi Arabia, and the coexistence of blaOXA
      23 and blaNDM-1 genes in this species in the country. Awareness of the role of
      international travel in the spread of carbapenem-resistant determinants in the
      Kingdom, as well as effective infection control interventions in hospitals and
      strict antimicrobial stewardship in healthcare facilities and the community are
      keys to combat the rise of carbapenemase producers in the Kingdom. 

PMID- 25569025
TI  - Negative Predictive Value of Transthoracic Core-Needle Biopsy: A Multicenter
      Study.
AB  - BACKGROUND: Specimens collected by CT scan-guided transthoracic core-needle
      biopsy (TTNB) are frequently used for the diagnosis of lung nodules, but the
      clinical value of negative results has not been sufficiently investigated. We
      sought to determine the negative predictive value (NPV) of TTNB specimens and
      investigate predictive factors of negative results. METHODS: All consecutive
      TTNBs performed in three centers between 2006 and 2012 were included. The medical
      charts of patients with nonmalignant TTNB specimens were reviewed and classified
      as true or false negatives. Binary logistic regression was used for multivariate
      analysis. RESULTS: Overall, findings from 980 TTNB specimens were included.
      Malignant disease was found in 79% (n = 777) of the cases, nonmalignant disease
      in 6% (n = 54), and "negative" results in 15% (n = 149). For the diagnosis of
      malignant disease, NPV was 51%. Estimated sensitivity, specificity, and accuracy
      were 89%, 99%, and 90%, respectively. The complication rate was 34% (life
      threatening complication in 6%). In multivariate analysis, predictive factors for
      a false-negative result were radiologist experience (adjusted OR [AOR], 0.996;
      95% CI, [0.994-0.998]), occurrence of a complication during the procedure (AOR,
      1.958; 95% CI, [1.202-3.187]), and moderate to high maximum standardized uptake
      value on PET scan (AOR, 7.657; 95% CI, [1.737-33.763]). In 24 cases, a second
      TTNB was performed at the same target. The complication rate was 33%, and TTNB
      specimens provided diagnosis in 95% of cases with a 67% NPV. CONCLUSIONS: One
      half of all "negative" TTNB specimen results were falsely negative for malignant
      diagnosis. Findings in tissue collected from a second TTNB at the same target
      provided a final diagnosis in most cases without increasing complication rates.

PMID- 25569026
TI  - Serum levels of vascular endothelial growth factor and related factors after
      intravitreous bevacizumab injection for retinopathy of prematurity.
AB  - IMPORTANCE: Intravitreous injections of bevacizumab (IVB) have been found to be
      effective for the treatment of retinopathy of prematurity (ROP). However, serum
      levels of vascular endothelial growth factor (VEGF) have been found to be
      suppressed for 2 weeks after IVB in patients with ROP. Changes in serum VEGF
      levels after IVB in patients with ROP may be important because VEGF also plays a
      role in the neurodevelopment of newborns. OBJECTIVE: To investigate the
      correlation of levels of VEGF and related growth factors with bevacizumab levels
      in the systemic circulation after IVB in patients with type 1 ROP. DESIGN,
      SETTING, AND PARTICIPANTS: We studied a prospective case series at an
      institutional referral center from December 1, 2011, through February 28, 2013.
      We enrolled patients with type 1 ROP who received IVB. We collected blood samples
      before and for as long as 8 weeks after IVB. The samples were tested for serum
      levels of bevacizumab and growth factors, including VEGF, VEGF receptor 1
      (VEGFR1), VEGFR2, Tie2, erythropoietin, transforming growth factor beta1,
      insulinlike growth factor type 1, angiopoietin 1, angiopoietin 2,
      angiopoietinlike 3, and angiopoietin 4. The serum concentrations of these factors
      were measured using enzyme-linked immunosorbent assays. MAIN OUTCOMES AND
      MEASURES: Serum levels of VEGF, bevacizumab, and the other growth factors before
      and for as long as 8 weeks after IVB. RESULTS: We enrolled 8 patients with type 1
      ROP. Bevacizumab levels were elevated 1 day after IVB in the 3 patients for whom
      measurements were available (mean [SD], 1425 [1010 (95% CI, 0-3934)] ng/mL; P =
      .13) and remained detectable in the serum as long as 8 weeks after IVB (285 ng/mL
      for the 1 patient with a measurement available). Serum VEGF levels were
      suppressed for the same period (mean [SD] level at 1 day after IVB, 379 [226 (95%
      CI, 190-568)] pg/mL for the 3 patients with measurements available; at 8 weeks,
      216 pg/mL for the 1 patient with a measurement available). We found a negative
      correlation between the serum levels of bevacizumab and VEGF in the patients with
      ROP who received IVB (r = -0.43 [95% CI, -0.67 to -0.10]; P = .01). No changes
      were identified in the serum levels of any of the other factors after IVB.
      Bevacizumab may interfere with the actual level of VEGF in the serum, and the
      total VEGF level in the serum cannot be determined when bevacizumab is present.
      Wide CIs were noted in the measurement of these factors, probably owing to the
      small number of patients enrolled in this study. CONCLUSIONS AND RELEVANCE: Serum
      VEGF levels were suppressed for 2 months after IVB in patients with type 1 ROP
      owing to the leakage of bevacizumab into the systemic circulation.

PMID- 25569027
TI  - Synthesis of oxazocenones via gold(I)-catalyzed 8-endo-dig hydroalkoxylation of
      alkynamides.
AB  - Several benzoxazocenones have been found to exhibit novel cellular activities. In
      the present study, we report a gold(I)-catalyzed 8-endo-dig hydroalkoxylation
      reaction of alkynamides to access analogous oxazocenone scaffolds. This
      methodology provided an advanced intermediate, which was elaborated to a des
      benzo analog of a bioactive benzoxazocenone. 

PMID- 25569028
TI  - High-dose barium impaction therapy for the recurrence of colonic diverticular
      bleeding: a randomized controlled trial.
AB  - OBJECTIVE: We compared the clinical efficacy of barium therapy and conservative
      therapy in preventing recurrence in patients with diverticular bleeding.
      BACKGROUND: Previous case reports have indicated that barium impaction therapy
      provides initial hemostasis for diverticular bleeding and prevention against
      rebleeding. METHODS: After spontaneous cessation of bleeding, patients were
      randomly assigned to conservative treatment (n = 27) or high-dose barium
      impaction therapy (n = 27). Patients were followed up for 1 year after enrollment
      of the last patient. The main outcome measure was rebleeding. RESULTS: Median
      follow-up period was 584.5 days. The probability of rebleeding at 30-day, 180
      day, 1-year, and 2-year follow-up in all patients was 3.7%, 14.8%, 28.4%, and
      32.7%, respectively. By group, probability at 1 year was 42.5% in the
      conservative group and 14.8% in the barium group (log-rank test, P = 0.04). After
      adjustment for a history of hypertension, the hazard ratio of rebleeding in the
      barium group was 0.34 (95% confidence interval, 0.12-0.98). No complications or
      laboratory abnormalities due to barium therapy were observed. Compared with the
      conservative group, the barium group had significantly (P < 0.05) fewer
      hospitalizations per patient (1.7 vs 1.2), units of blood transfused (1.9 vs
      0.7), colonoscopies (1.4 times vs 1.1 times), and hospital stay days (15 days vs
      11 days) during the follow-up period. No patients died and none required
      angiographic or surgical procedures in either group. CONCLUSIONS: High-dose
      barium impaction therapy was effective in the long-term prevention of recurrent
      bleeding, and reduced the frequency of rehospitalization and need for blood
      transfusion and colonoscopic examination. ClinicalTrials.gov Identifier, UMIN
      000002832.

PMID- 25569029
TI  - Comparison between clinical registry and medicare claims data on the
      classification of hospital quality of surgical care.
AB  - OBJECTIVE: To compare the classification of hospital statistical outlier status
      as better or worse performance than expected for postoperative complications
      using Medicare claims versus clinical registry data. BACKGROUND: Controversy
      remains as to the most favorable data source for measuring postoperative
      complications for pay-for-performance and public reporting polices. METHODS:
      Patient-level records (2005-2008) were linked between the American College of
      Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and Medicare
      inpatient claims. Hospital statistical outlier status for better or worse
      performance than expected was assessed using each data source for superficial
      surgical site infection (SSI), deep/organ-space SSI, any SSI, urinary tract
      infection, pneumonia, sepsis, deep venous thrombosis, pulmonary embolism, venous
      thromboembolism, and myocardial infarction by developing hierarchical
      multivariable logistic regression models. Kappa statistics and correlation
      coefficients assessed agreement between the data sources. RESULTS: A total of 192
      hospitals with 110,987 surgical patients were included. Agreement on hospital
      rank for complication rates between Medicare claims and ACS-NSQIP was poor-to
      moderate (weighted kappa: 0.18-0.48). Of hospitals identified as statistical
      outliers for better or worse performance by Medicare claims, 26% were also
      identified as outliers by ACS-NSQIP. Of outliers identified by ACS-NSQIP, 16%
      were also identified as outliers by Medicare claims. Agreement between the data
      sources on hospital outlier status classification was uniformly poor (weighted
      kappa: -0.02-0.34). CONCLUSIONS: Despite using the same statistical methodology
      with each data source, classification of hospital outlier status as better or
      worse performance than expected for postoperative complications differed
      substantially between ACS-NSQIP and Medicare claims.

PMID- 25569030
TI  - Remission of type 2 diabetes after Roux-en-Y gastric bypass or sleeve gastrectomy
      is associated with a distinct glycemic profile.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG) have
      been associated with a high remission rate of type 2 diabetes mellitus (T2DM).
      However, whether such remission is associated with full restoration of
      postprandial glucose profile and/or the potentially nonrestored glycemic profile
      is associated with altered beta cell function, and relapse of T2DM over time is
      unknown. METHODS: Cross-sectional studies comparing (1) glucose and
      proinsulin/insulin response to a standardized liquid mixed meal (SLMM) challenge
      (n = 31), (2) glucose response in normal living conditions assessed using
      continuous glucose monitoring (CGM) (n = 16), and prospective observational study
      comparing (3) rates of relapse of T2DM after surgery (n = 232) in subjects with
      remission of T2DM ensuing RYGBP or SG. RESULTS: In RYGB individuals, SLMM
      elicited faster and sharper rise in plasma glucose compared with SG, with 88.2%
      and 42.9% of the study subjects presenting respectively a peak glucose more than
      180 mg/dL (all, P < 0.05). During CGM, average percent time in hyperglycemic and
      hypoglycemic range was larger in RYGBP (respectively, 4.6% and 12.7%) compared
      with SG subjects (respectively, 0.4% and 3.2%; both P < 0.05). However, (1) no
      differences were found in fasting or stimulated proinsulin/insulin ratio, and (2)
      higher rates of T2DM relapse were observed after SG (hazard ratio: 2.339; P =
      0.034). CONCLUSIONS: Remission of T2DM after RYGBP and SG is associated with
      distinct glycemic profiles. However, longer time spent in hyperglycemia and in
      hypoglycemia after RYGBP compared with SG is not associated with persistence of
      altered beta cell function or higher rates of relapse of T2DM over time.

PMID- 25569031
TI  - Bio-desulfurization of biogas using acidic biotrickling filter with dissolved
      oxygen in step feed recirculation.
AB  - Triple stage and single stage biotrickling filters (T-BTF and S-BTF) were
      operated with oxygenated liquid recirculation to enhance bio-desulfurization of
      biogas. Empty bed retention time (EBRT 100-180 s) and liquid recirculation
      velocity (q 2.4-7.1 m/h) were applied. H2S removal and sulfuric acid recovery
      increased with higher EBRT and q. But the highest q at 7.1 m/h induced large
      amount of liquid through the media, causing a reduction in bed porosity in S-BTF
      and H2S removal. Equivalent performance of S-BTF and T-BTF was obtained under the
      lowest loading of 165 gH2S/m(3)/h. In the subsequent continuous operation test,
      it was found that T-BTF could maintain higher H2S elimination capacity and
      removal efficiency at 175.6+/-41.6 gH2S/m(3)/h and 89.0+/-6.8% versus S-BTF at
      159.9+/-42.8 gH2S/m(3)/h and 80.1+/-10.2%, respectively. Finally, the
      relationship between outlet concentration and bed height was modeled. Step
      feeding of oxygenated liquid recirculation in multiple stages clearly
      demonstrated an advantage for sulfide oxidation.

PMID- 25569032
TI  - Bacterial community compositions of coking wastewater treatment plants in steel
      industry revealed by Illumina high-throughput sequencing.
AB  - In this study, Illumina high-throughput sequencing was used to reveal the
      community structures of nine coking wastewater treatment plants (CWWTPs) in China
      for the first time. The sludge systems exhibited a similar community composition
      at each taxonomic level. Compared to previous studies, some of the core genera in
      municipal wastewater treatment plants such as Zoogloea, Prosthecobacter and Gp6
      were detected as minor species. Thiobacillus (20.83%), Comamonas (6.58%), Thauera
      (4.02%), Azoarcus (7.78%) and Rhodoplanes (1.42%) were the dominant genera shared
      by at least six CWWTPs. The percentages of autotrophic ammonia-oxidizing bacteria
      and nitrite-oxidizing bacteria were unexpectedly low, which were verified by both
      real-time PCR and fluorescence in situ hybridization analyses. Hierarchical
      clustering and canonical correspondence analysis indicated that operation mode,
      flow rate and temperature might be the key factors in community formation. This
      study provides new insights into our understanding of microbial community
      compositions and structures of CWWTPs. 

PMID- 25569033
TI  - Combined pretreatment using ozonolysis and ball milling to improve enzymatic
      saccharification of corn straw.
AB  - Two clean pretreatments, ozonolysis (OZ) and planetary ball milling (BM) were
      applied separately and in combination to improve the enzymatic hydrolysis of corn
      straw. Pretreatment of corn straw by OZ and BM alone improved the enzymatic
      hydrolysis significantly, primarily through delignification and decrystallization
      of cellulose, respectively. When combined, OZ-BM and BM-OZ pretreatments made the
      enzymatic hydrolysis more efficient. The glucose and xylose yield of corn straw
      treated with OZ for 90 min followed by BM for 8 min (OZ90-BM8) reached to 407.8
      and 101.9 mg/g-straw, respectively under cellulase loading of 15 FPU/g-straw,
      which was fivefold more than that of untreated straw. Under much lower cellulase
      loading of 1.5 FPU/g-straw, the glucose and xylose yield of treated straw OZ90
      BM8 remained at 416.0 and 108.4 mg/g-straw, respectively, while the yield of
      untreated straw decreased. These findings indicate that the combined OZ-BM can be
      used as a promising pretreatment for corn straw.

PMID- 25569034
TI  - Astaxanthin and Corni Fructus protect against diabetes-induced oxidative stress,
      inflammation, and advanced glycation end product in livers of streptozotocin
      induced diabetic rats.
AB  - This study was conducted to compare the protective effects of astaxanthin (ASX)
      with Corni Fructus (CF) against diabetes-induced pathologies such as oxidative
      stress-induced inflammation and advanced glycation end product (AGE) formation in
      the liver of type 1 diabetic rats. ASX (50 mg/kg body weight/day) or CF (200
      mg/kg body weight/day) was orally administered every day for 18 days to
      streptozotocin (STZ)-induced diabetic rats, and their effects were compared with
      nondiabetic and diabetic control rats. The administration of CF, but not ASX,
      decreased both the elevated serum and hepatic glucose concentration in diabetic
      rats. In diabetic rats, increased levels of AGE, reactive oxygen species, and
      lipid peroxidation were significantly decreased by treatment with both ASX and CF
      in the liver of diabetic rats. STZ treatment markedly augmented the protein
      expressions of AGE, and both ASX and CF efficiently attenuated these increases in
      hepatic protein expressions. In addition, oxidative stress and proinflammatory
      protein expressions were upregulated in the diabetic rats. On the contrary, these
      upregulations of protein expressions were decreased by the administration of ASX
      or CF. These results suggest that the inhibitory effect of ASX on diabetes
      induced hepatic dysfunction could be derived from the blocking of AGE formation
      and further anti-inflammation and that CF exhibited beneficial effects through
      the attenuation of hyperglycemia, and thus the inhibition of AGE formation and
      the inflammatory responses. Therefore, ASX as well as CF may help prevent ongoing
      diabetes-induced hepatic injury.

PMID- 25569035
TI  - Carbon monoxide release properties and molecular structures of
      phenylthiolatomanganese(I) carbonyl complexes of the type [(OC)4Mn(MU-S-aryl)]2.
AB  - Several phenylthiolatomanganese carbonyl complexes of the type [(OC)4Mn(MU-SR)]2
      (R = Ph (), C6H4-4-CH3 (), C6H4-4-CF3 (), C6H4-4-F (), C6H4-4-Cl (), C6H4-4-OMe
      (), C6F5 (), and CH2C6H4-4-Cl ()) have been prepared via the reaction of
      Mn2(CO)10 with diaryldisulfane or via the reaction of [(OC)5MnBr] with
      arylthiols. These complexes lose two carbon monoxide molecules quite easily
      yielding tetranuclear [(OC)3Mn(MU3-SR)]4 (). Derivatives with fluoro-substituted
      aryl groups commonly form mixtures of dinuclear and tetranuclear which can
      quantitatively be converted to by heating of the corresponding reaction mixtures.
      A unique trinuclear structure is found for the mesityl derivative [(OC)4Mn(MU
      SMes)]3 () which is maintained in solution as verified by IR and NMR
      spectroscopy. Traces of an already known dinuclear by-product of the type
      [(OC)3Mn(MU-SC6H3(-4-Me)-2-SC6H4-4-Me)]2 () have been structurally characterized.
      The suitability of [(OC)4Mn(MU-SPh)]2 () as a CO releasing molecule (CORM) for
      the administration of carbon monoxide has been studied. Two CO molecules are
      released upon dissolving in strongly Lewis basic solvents L, yielding
      [(OC)3Mn(L)(MU-SPh)]2, which liberates all the remaining CO molecules upon
      irradiation (photoCORM behavior). 

PMID- 25569037
TI  - Medullary thyroid cancer: an update for surgeons.
AB  - Medullary thyroid carcinoma is uncommon but accounts for approximately 4 to 5 per
      cent of all thyroid cancers. Although most cases are sporadic, close to one
      fourth of cases result from germline mutations in the RET proto-oncogene. These
      mutations are clinically important because they predict the earliest age of
      medullary thyroid cancer diagnosis and clinical aggressiveness, which guide
      individualized management. This review covers the presentation, diagnosis,
      workup, current management, and future directions of the management of medullary
      thyroid carcinoma. Today's chance for cure depends on early and appropriate
      surgical resection. Further investigation of the cellular signaling pathways
      shown to be essential for the growth and spread of medullary thyroid carcinoma
      remains an active field with hope for providing targeted systemic therapy for
      patients with progressive disease. 

PMID- 25569038
TI  - Racial disparities in the use of laparoscopic cholecystectomy still exist!

PMID- 25569039
TI  - Spontaneous mesenteric hematoma associated with recurrent incarcerated inguinal
      hernia.

PMID- 25569036
TI  - Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer
      metastasis through targeting Rap1B.
AB  - Glucocorticoids are widely used in conjunction with chemotherapy for ovarian
      cancer to prevent hypersensitivity reactions. Here we reveal a novel role for
      glucocorticoids in the inhibition of ovarian cancer metastasis. Glucocorticoid
      treatments induce the expression of miR-708, leading to the suppression of Rap1B,
      which result in the reduction of integrin-mediated focal adhesion formation,
      inhibition of ovarian cancer cell migration/invasion and impaired abdominal
      metastasis in an orthotopic xenograft mouse model. Restoring Rap1B expression
      reverts glucocorticoid-miR-708 cascade-mediated suppression of ovarian cancer
      cell invasion and metastasis. Clinically, low miR-708 and high Rap1B are found in
      late-state ovarian tumours, as compared with normal, and patients with high miR
      708 show significantly better survival. Overall, our findings reveal an
      opportunity for glucocorticoids and their downstream mediators, miR-708 or Rap1B,
      as therapeutic modalities against metastatic ovarian epithelial cancer. 

PMID- 25569040
TI  - Does perioperative local cooling improve immediate outcomes after ambulatory open
      inguinal hernia repair?

PMID- 25569041
TI  - An unusual case of obstruction after Roux-en-Y gastric bypass.

PMID- 25569042
TI  - Dr. Mary Edwards Walker: years ahead of her time.

PMID- 25569043
TI  - Tranexamic acid: familiarity and use in the Level II trauma hospital.

PMID- 25569044
TI  - Cecal diverticulitis mimicking cecal carcinoma.

PMID- 25569045
TI  - Ernest Amory Codman and the End-result System.
AB  - Ernest Amory Codman had an early penchant fondness for recording surgical
      complications and analyzing these recordings to determine a surgeon's ability
      along with a hospital's efficiency. This idea and the actions that followed suit
      in his career were not well received by his fellow colleagues. However, Codman's
      influence and spirit remained and helped shape important institutions in American
      medicine such as the The Joint Commission on Accreditation of Healthcare
      Organizations. 

PMID- 25569046
TI  - Transomental prolapse of Meckel's diverticulum.

PMID- 25569047
TI  - Surgeons and their tools: a history of surgical instruments and their innovators.
      Part III: the medical student's best friend-retractors.
AB  - This is the third of five manuscripts reviewing the historical origins of some of
      the more commonly used surgical instruments and takes "time out" to remind
      current surgeons about the surgical pioneers on whose shoulders they now stand
      and whose inventions they now use. 

PMID- 25569048
TI  - Laparoscopic repair of a giant paraesophageal hernia containing pancreas.

PMID- 25569049
TI  - Appendiceal Dieulafoy lesion: an unusual cause of massive lower gastrointestinal
      bleeding.

PMID- 25569050
TI  - The burden of the U.S. crisis in the surgical critical care workforce and
      workflow.
AB  - There will be a 46 per cent shortage of intensivists by 2030. Currently, only 3
      per cent of U.S. critical care is provided by surgeon-intensivists. Measurement
      of the current workload is needed to understand the ramifications of the expected
      shortage of surgeon-intensivists. The purpose of this study is to evaluate the
      self-reported workload of U.S. surgeon-intensivists. Over a 2-month period, a
      voluntary and anonymous survey of the surgery section of the Society of Critical
      Care Medicine was performed using Survey Monkey. Only surgeons were invited to
      participate. We assessed personnel resources and surgeon-intensivists workload in
      the intensive care unit (ICU) and on their postcall day. Two hundred sixty-two
      persons responded. Sixty-nine per cent had administrative responsibilities and 42
      per cent covered bed allocation/transfer center duties while in the ICU. Seventy
      six per cent covered trauma and general surgery call and 72 per cent covered the
      outpatient clinic or had elective surgery cases while responsible for the ICU.
      Only 14 per cent had no other responsibilities. Twenty-one per cent did not round
      with residents and 50 per cent did not round with a fellow. Thirty-six per cent
      did not work with advanced practitioners. The majority of surgeon-intensivists
      have significant responsibilities in addition to providing ICU care. This
      workload should be factored into the expected shortage of surgical intensivists
      relative to the expected increase in critical care demand. 

PMID- 25569051
TI  - Simultaneous stimulation of multiple parasympathetic afferents may have a
      synergistic effect causing severe bradycardia.

PMID- 25569052
TI  - Appendiceal torsion presenting as a right lower quadrant mass.

PMID- 25569053
TI  - Subcutaneous suture can accelerate wound healing of lower midline incision: a
      randomized controlled trial.
AB  - Poor wound healing is one of the most common complications after laparotomy,
      especially in lower abdominal midline incisions. The aims of this trial are to
      assess the value of subcutaneous suture and identify risk factors to prevent poor
      wound healing. From October 2010 to October 2011, a total of 180 patients were
      randomized to the subcutaneous suture group (n = 89) or control group (n = 91)
      after laparotomy with a lower midline incision. Univariate and multivariate
      analyses were performed to determine the predictive significance of variables of
      poor wound healing. Patients' demographics, preoperative laboratory values, and
      operative details were comparable between the two groups. The overall rate of
      poor wound healing was 16.7 per cent (30 of 180). Patients randomized to
      subcutaneous suture group (n = 89) had poor healing in 10.1 per cent (nine of 89)
      and those without suture (n = 91) in 23.1 per cent (21 of 91) (P = 0.020).
      Multivariate logistic regression analysis revealed that American Society of
      Anesthesiologists (ASA) score (3 to 4) (odds ratio [OR], 2.933), subcutaneous
      suture (OR, 0.323), and blood loss (greater than 200 mL) (OR, 5.995) were
      independent risk factors for poor wound healing. Subcutaneous suture can
      effectively accelerate wound healing. Nonsubcutaneous suture, ASA score (3 to 4),
      and blood loss (greater than 200 mL) are independent risk factors for poor would
      healing. 

PMID- 25569054
TI  - Thyroglossal duct carcinoma.

PMID- 25569055
TI  - Abdominal distention and early satiety, pancreaticoduodenectomy for lymphangioma.

PMID- 25569056
TI  - Multidisciplinary approach to an unusual adult presentation of exstrophy
      epispadias complex.

PMID- 25569057
TI  - Usefulness of lung biopsy in pediatric pulmonary conditions.
AB  - Lung biopsy, performed as a diagnostic procedure in children with pulmonary
      disease to guide treatment, may not provide a diagnosis or change therapy. We
      therefore reviewed our experience with the procedure to determine its use. We
      reviewed all children undergoing lung biopsy at two large children's hospitals,
      2001 to 2010. Lesions were categorized as either diffuse or localized based on
      final radiological interpretations. Pathological interpretations and subsequent
      treatment regimens were reviewed for specificity of diagnoses and any changes in
      therapy. Of 99 patients, there were 14 diffuse and 85 localized pulmonary
      lesions. Biopsy confirmed the radiological diagnosis in 29 (29%), 71 per cent
      (70) receiving a new histopathological diagnosis, or a definitive one from a
      range or radiological possibilities, both diffuse (10 of 14) and diffuse lesions
      (60 of 85, both 71%). Forty-five per cent (44 of 99) had sufficient clinical data
      to ascertain treatment before and after biopsy. A significant change in treatment
      occurred in only 16 per cent (seven of 44) without a significant difference
      between diffuse (33% [three of nine]) and localized (11% [four of 35]) lesions (P
      = 0.38). Twenty-five per cent (25 of 99) of patients undergoing lung biopsy died.
      Lung biopsy is performed for conditions with a high mortality rate. The procedure
      yields a definitive diagnosis in the majority of cases but infrequently changes
      therapy. 

PMID- 25569058
TI  - Green urine in the intensive care unit: is this clinically relevant?

PMID- 25569059
TI  - Postpartum transabdominal laparoscopic adrenalectomy for pheochromocytoma
      presenting with abruption and hypertensive emergency.

PMID- 25569060
TI  - Long-term quality-of-life improvement in gastric banding patients from body
      contouring surgery.
AB  - Following my prior study of long-term results after laparoscopic gastric banding
      concerning operative outcome and complications involving the gastric band itself,
      I now focus on long-term quality-of-life improvement in the same study group
      after body-contouring surgery. As determined from our electronic patient data
      system, 72 patients from the former study group subsequently sought body
      contouring surgery at our hospital after successful weight loss. Patients were
      enrolled in a telephone interview and asked about their expectations and body
      image before and after postbariatric aesthetic surgery and how it altered their
      well-being in addition to the weight loss achieved with the gastric band. All
      patients undergoing postbariatric aesthetic surgery felt extremely uneasy with
      the hanging skin resulting from weight reduction. Patients cannot imagine the
      degree of dissatisfaction they will experience from the sagging skin that comes
      with weight loss. Hardly any patient expected fewer scars than he ultimately had
      after body-contouring surgery and reported an extreme improvement in body image.
      Gastric banding should not be performed without informing patients about the need
      for postbariatric body-contouring surgery, because most patients not forewarned
      suffer greatly from their body image after weight loss. 

PMID- 25569061
TI  - Parathyroidectomy improves fracture nonunion in hyperparathyroidism.

PMID- 25569062
TI  - Esophagogastric fistula.

PMID- 25569063
TI  - An argument for routinely performing liver biopsy with bariatric procedures.

PMID- 25569064
TI  - Anastomotic leakage after anterior resection for rectal cancer with mesorectal
      excision: incidence, risk factors, and management.
AB  - We investigated risk factors and prognostic implications of symptomatic
      anastomotic leakage after anterior resection for rectal cancer, and the influence
      of a diverting stoma. Our retrospective review of prospective collected data
      analyzed 475 patients who underwent anterior resection for rectal cancer. Uni-
      and multivariate analysis was made between anastomotic leakage and patient,
      tumor, and treatment variables, either for the overall group (n = 475) and in the
      midlow rectal cancer subgroup (n = 291). Overall rate of symptomatic leakage was
      9 per cent (43 of 475) with no related postoperative mortality. At univariate
      analysis, significant factors for leak were a tumor less than 6 cm from the anal
      verge (13.7 vs 6.6%; P = 0.011) and intraoperative transfusions (16.9 vs 4.3%; P
      = 0.001). Similar results were observed in the midlow rectal cancer subgroup. At
      multivariate analysis, no parameter resulted in being an independent prognostic
      factor for risk of leakage. In patients with a leakage, a temporary enterostomy
      considerably reduced the need for reoperation (12.5 vs 77.8%; P < 0.0001) and the
      risk of a permanent stoma (18.7 vs 28.5%; P = 0.49). The incidence of anastomotic
      failure increases for lower tumors, whereas it is not influenced by radiotherapy.
      Defunctioning enterostomy does not influence the leak rate, but it mitigates
      clinical consequences. 

PMID- 25569065
TI  - Predictors of recurrence in patients diagnosed with ductal carcinoma in situ.
AB  - Although patients diagnosed with ductal carcinoma In Situ (DCIS) enjoy a
      favorable prognosis, recurrence after definitive management does occur in a
      subset of these patients. Factors influencing the development of recurrence
      remain poorly understood. A retrospective chart review of 205 consecutive
      patients who presented to an academic breast center with DCIS from 2000 to 2003
      was conducted under an Institutional Review Board-approved protocol. With a
      median follow-up of 8.5 years, 14 (6.8%) of the 205 patients who presented with
      DCIS between 2000 and 2003 had a recurrence of their DCIS. The median age of all
      patients at the time of diagnosis of their initial DCIS was 55.5 years (range,
      35.8 to 88.9 years). Patients who experienced tumor recurrence were more likely
      to have Grade 3 DCIS on initial diagnosis compared with patients without
      recurrence (72.7 vs 35.4%, P = 0.032). The odds ratio of tumor recurrence for
      high-grade compared with low-grade DCIS was 4.39. Patient age, race, tumor size,
      tumor histologic subtype, or histopathologic features was not associated with
      recurrence. Patients with high-grade DCIS are more likely to recur than patients
      with low-grade DCIS, and this seems to be more predictive of recurrence than
      other clinicopathologic markers. 

PMID- 25569066
TI  - Is cirrhosis a contraindication to laparoscopic cholecystectomy?
AB  - Laparoscopic cholecystectomy is the gold standard treatment for the vast majority
      of patients with symptomatic cholelithiasis. Although cirrhotic patients are
      twice as likely to develop gallstones as compared with noncirrhotic patients,
      cirrhosis has historically been considered a relative, if not absolute,
      contraindication to laparoscopic cholecystectomy. More recently a number of
      authors have reported on the safety of laparoscopic cholecystectomy in cirrhotic
      patients. We reviewed our patients retrospectively and assessed the safety of
      laparoscopic cholecystectomy in cirrhotic patients as compared with noncirrhotics
      at a large liver transplant center. A retrospective longitudinal cohort study was
      conducted of all laparoscopic cholecystectomies performed by our surgical group
      between August 2002 and April 2011. Of 63 patients undergoing laparoscopic
      cholecystectomy, 32 (51%) were cirrhotic. Of the 30 for whom a Child score could
      be calculated, 11 (34%) were Child A, 14 (44%) were Child B, and five (16%) were
      Child C. The morbidity rate was 33 per cent and mortality rate was 2 per cent.
      Length of stay, conversion rates, 30-day readmission rates, and morbidity and
      mortality rates were not significantly different between the cirrhotic and
      noncirrhotic groups. There was a trend toward higher complication rates in Child
      C cirrhotics. Our results indicate that laparoscopic cholecystectomy can be
      performed with acceptable morbidity and mortality in carefully selected cirrhotic
      patients. 

PMID- 25569067
TI  - Total body surface area overestimation at referring institutions in children
      transferred to a burn center.
AB  - Total body surface area (TBSA) burned is a powerful descriptor of burn severity
      and influences the volume of resuscitation required in burn patients. The
      incidence and severity of TBSA overestimation by referring institutions (RIs) in
      children transferred to a burn center (BC) are unclear. The association between
      TBSA overestimation and overresuscitation is unknown as is that between TBSA
      overestimation and outcome. The trauma registry at a BC was queried over 7.25
      years for children presenting with burns. TBSA estimate at RIs and BC, total
      fluid volume given before arrival at a BC, demographic variables, and clinical
      variables were reviewed. Nearly 20 per cent of children arrived from RIs without
      TBSA estimation. Nearly 50 per cent were overestimated by 5 per cent or greater
      TBSA and burn sizes were overestimated by up to 44 per cent TBSA. Average TBSA
      measured at BC was 9.5 +/- 8.3 per cent compared with 15.5 +/- 11.8 per cent as
      measured at RIs (P < 0.0001). Burns between 10 and 19.9 per cent TBSA were
      overestimated most often and by the greatest amounts. There was a statistically
      significant relationship between overestimation of TBSA by 5 per cent or greater
      and overresuscitation by 10 mL/kg or greater (P = 0.02). No patient demographic
      or clinical factors were associated with TBSA overestimation. Education efforts
      aimed at emergency department physicians regarding the importance of always
      calculating TBSA as well as the mechanics of TBSA estimation and calculating
      resuscitation volume are needed. Further studies should evaluate the association
      of TBSA overestimation by RIs with adverse outcomes and complications in the
      burned child. 

PMID- 25569068
TI  - Outcomes of hepatic resection for large hepatocellular carcinoma: special
      reference to postoperative recurrence.
AB  - Safety and efficacy of hepatic resection for large hepatocellular carcinomas
      (HCCs 10 cm or greater in diameter) remain controversial. Surgical results of
      patients with HCCs 10 cm or greater (n = 24) who underwent hepatic resection over
      an 11-year period were compared with those of patients with HCCs less than 10 cm
      (n = 291). There was no significant difference in mortality between the two
      groups (P > 0.99). Overall 5-year survival rate was 44.6 per cent among patients
      with HCCs 10 cm or greater and 70.5 per cent among those with HCCs less than 10
      cm (P = 0.010); however, there was no significant difference in disease-free
      survival rate between the two groups (P = 0.16). Incidence of synchronous intra-
      and extrahepatic recurrence was higher in patients with HCCs 10 cm or greater
      than in those with HCCs less than 10 cm (P = 0.0012). Macrovascular invasion
      alone was an independent risk factor for poor prognosis (hazard ratio [HR],:
      11.1) and recurrence (HR, 6.02) after hepatic resection for HCCs 10 cm or
      greater, which was correlated with synchronous intra- and extrahepatic
      recurrence. Hepatic resection for large HCCs is safe and efficacious. However,
      incidence of synchronous intra- and extrahepatic recurrence is high, especially
      in patients with macrovascular invasion. 

PMID- 25569069
TI  - Doing more: trends in breast cancer surgery, 2005 to 2011.
AB  - An increasing number of women may be choosing mastectomy over breast-conserving
      surgery for breast cancer as well as undergoing more bilateral resection,
      immediate reconstruction, and prophylactic operations. Women who had breast
      cancer operations between 2005 and 2011 were selected from the National Surgical
      Quality Improvement Program database. Annual trends were explored using robust
      Poisson multivariable regression as were predictors for mastectomy versus breast
      conserving surgery. A total of 85,401 women were identified. Mastectomy increased
      from 2005 to 2011, starting at 40 per cent in 2005 and peaking at 51 per cent in
      2008 (P < 0.001). Bilateral resection, immediate reconstruction, and prophylactic
      mastectomy also increased (all P < 0.001). Independent predictors of mastectomy
      included young age, Asian race, invasive cancer (vs carcinoma in situ), bilateral
      resection, axillary dissection, higher American Society of Anesthesiologists
      class, and lower body mass index (all P < 0.001). There was an increase in
      mastectomy, bilateral resection, immediate reconstruction, and prophylactic
      mastectomy from 2005 to 2011. 

PMID- 25569070
TI  - Airway pressures as surrogate estimates of intra-abdominal pressure.
AB  - Intra-abdominal pressure (IAP) measurements are essential to the diagnosis and
      management of patients with intra-abdominal hypertension (IAH) and abdominal
      compartment syndrome (ACS). Peak inspiratory pressure (PIP), plateau pressure
      (Pplat), and mean airway pressure (Paw) are used by some surgeons as surrogate
      estimates of IAP during abdominal closure. Thirty mechanically ventilated
      surgical/trauma patients with risk factors for IAH/ACS underwent simultaneous
      triplicate measurements of PIP, Pplat, Paw, and IAP. PIP, Pplat, and Paw were
      compared with IAP using both coefficient of determination and Bland and Altman
      analysis. The coefficient of determination for each airway pressure in predicting
      change in IAP was: PIP 5 per cent (P = 0.24), Pplat 17 per cent (P = 0.02), and
      Paw 15 per cent (P = 0.03). Bland and Altman analysis identified that marked
      variability exists between airway pressure and IAP measurements: PIP 19.3 +/-
      18.7 mmHg, Pplat 11.1 +/- 13.7 mmHg, and Paw 2.0 +/- 9.8 mmHg. Airway pressures
      do not accurately reflect IAP and cannot be substituted for IAP measurements in
      patients at risk for IAH/ACS.

PMID- 25569072
TI  - Xenogenic (porcine) acellular dermal matrix promotes growth of granulation
      tissues in the wound healing of Fournier gangrene.
AB  - This article investigates the application values of Xenogenic (porcine) acellular
      dermal matrix (XADM) in preparation of a Fournier gangrene wound bed. Thirty-six
      consecutive cases of patients with Fournier gangrene between 2002 and 2012 were
      enrolled in our department of our hospital. The patients were divided into two
      groups according to different methods of wound bed preparation after surgical
      debridement, including the experimental group (17 cases) and the control group
      (19 cases). The wounds in the experimental group were covered with XADM after
      surgical wound debridement, whereas the wounds were cleaned with hydrogen
      peroxide and sodium hypochlorite solution (one time/day) in the control group.
      The wound bed preparation time and hospital stay were then compared in the two
      groups. The wound preparation time was 13.64 +/- 1.46 days and hospitalization
      period was 26.06 +/- 0.83 days in the experimental XADM group. In the control
      group, the wound bed preparation time and hospitalization period were 22.37 +/-
      1.38 and 38.11 +/- 5.60 days, respectively. The results showed statistical
      differences between these two groups. When used in wound debridement after
      Fournier gangrene, XADM protects interecological organizations, promotes the
      growth of granulation tissues, and maximally retains function and morphology of
      the perineum and penis. 

PMID- 25569071
TI  - Management of femoral vessel injuries: a 6-year single-center experience.
AB  - Femoral vessel injuries are a familiar injury treated in busy urban trauma
      centers. The majority of peripheral vascular injuries to the lower extremity
      occur most commonly to the femoral vessels. The increasing incidence of civilian
      violence provides an opportunity to perform a comprehensive review and management
      of these injuries. 

PMID- 25569073
TI  - Real-time cadaveric laparoscopy and laparoscopic video demonstrations in gross
      anatomy: an observation of impact on learning and career choice.
AB  - Medical curricula are continually evolving and increasing clinical relevance.
      Gross anatomy educators have tested innovations to improve the clinical potency
      of anatomic dissection and found that clinical correlations are an effective
      method to accomplish this goal. Recently, surgical educators defined a role for
      laparoscopy in teaching anatomy. We aimed to expand this role by using surgical
      educators to create clinical correlates between gross anatomy and clinical
      surgery. We held supplements to traditional anatomy open dissection for medical
      students, including viewing prerecorded operative footage and live laparoscopic
      dissection performed on cadavers. The main outcome measures were assessed through
      pre- and postsession surveys. Greater than 75 per cent of students found the
      demonstrations highly valuable, and students perceived a significant increase in
      their understanding of abdominopelvic anatomy (P < 0.01). Additionally, 62 per
      cent of students with previous interest in surgery and 10 per cent of students
      without previous interest in surgery reported increased interest in pursuing
      surgical careers. Our demonstrations advance the use of minimally invasive
      surgical technology to teach gross anatomy. Live laparoscopic demonstrations
      augment traditional anatomic instruction by reinforcing the clinical relevance of
      abdominopelvic anatomy. Additionally, laparoscopic demonstrations generate
      interest in surgery that would otherwise be absent in the preclinical years. 

PMID- 25569074
TI  - Current management of gallbladder polyp: should cholecystectomy be recommended
      for polyps smaller than 10 mm?

PMID- 25569075
TI  - All-terrain vehicle accidents in children.

PMID- 25569076
TI  - Timing of angioembolization does not affect patient outcome.

PMID- 25569077
TI  - The acute management of a thoracic aorta gunshot wound and missile embolization
      with endovascular stent grafting and open missile retrieval.

PMID- 25569078
TI  - Immune memory to Sudan virus: comparison between two separate disease outbreaks.
AB  - Recovery from ebolavirus infection in humans is associated with the development
      of both cell-mediated and humoral immune responses. According to recent studies,
      individuals that did not survive infection with ebolaviruses appear to have
      lacked a robust adaptive immune response and the expression of several early
      innate response markers. However, a comprehensive protective immune profile has
      yet to be described. Here, we examine cellular memory immune responses among
      survivors of two separate Ebolavirus outbreaks (EVDs) due to Sudan virus (SUDV)
      infection in Uganda-Gulu 2000-2001 and Kibaale 2012. Freshly collected blood
      samples were stimulated with inactivated SUDV, as well as with recombinant SUDV
      or Ebola virus (EBOV) GP (GP1-649). In addition, ELISA and plaque reduction
      neutralization assays were performed to determine anti-SUDV IgG titers and
      neutralization capacity. Cytokine expression was measured in whole blood cultures
      in response to SUDV and SUDV GP stimulation in both survivor pools, demonstrating
      recall responses that indicate immune memory. Cytokine responses between groups
      were similar but had distinct differences. Neutralizing, SUDV-specific IgG
      activity against irradiated SUDV and SUDV recombinant proteins were detected in
      both survivor cohorts. Furthermore, humoral and cell-mediated crossreactivity to
      EBOV and EBOV recombinant GP1-649 was observed in both cohorts. In conclusion,
      immune responses in both groups of survivors demonstrate persistent recognition
      of relevant antigens, albeit larger cohorts are required in order to reach
      greater statistical significance. The differing cytokine responses between Gulu
      and Kibaale outbreak survivors suggests that each outbreak may not yield
      identical memory responses and promotes the merits of studying the immune
      responses among outbreaks of the same virus. Finally, our demonstration of cross
      reactive immune recognition suggests that there is potential for developing cross
      protective vaccines for ebolaviruses. 

PMID- 25569079
TI  - Posttraumatic stress disorder post Iraq and Afghanistan: prevalence among
      military subgroups.
AB  - A large body of research has been produced in recent years investigating
      posttraumatic stress disorder (PTSD) among military personnel following
      deployment to Iraq and Afghanistan, resulting in apparent differences in PTSD
      prevalence. We compare prevalence estimates for current PTSD between military
      subgroups, providing insight into how groups may be differentially affected by
      deployment. Systematic literature searches using the terms PTSD, stress disorder,
      and acute stress, combined with terms relating to military personnel, identified
      49 relevant papers. Studies with a sample size of less than 100 and studies based
      on data for treatment seeking or injured populations were excluded. Studies were
      categorized according to theatre of deployment (Iraq or Afghanistan), combat and
      noncombat deployed samples, sex, enlistment type (regular or reserve and [or]
      National Guard), and service branch (for example, army, navy, and air force).
      Meta-analysis was used to assess PTSD prevalence across subgroups. There was
      large variability in PTSD prevalence between studies, but, regardless of
      heterogeneity, prevalence rates of PTSD were higher among studies of Iraq
      deployed personnel (12.9%; 95% CI 11.3% to 14.4%), compared with personnel
      deployed to Afghanistan (7.1%; 95% CI 4.6% to 9.6%), combat deployed personnel,
      and personnel serving in the Canadian, US, or UK army or the navy or marines
      (12.4%; 95% CI 10.9% to 13.4%), compared with the other services (4.9%; 95% CI
      1.4% to 8.4%). Contrary to findings from within-study comparisons, we did not
      find a difference in PTSD prevalence for regular active-duty and reserve or
      National Guard personnel. Categorizing studies according to deployment location
      and branch of service identified differences among subgroups that provide further
      support for factors underlying the development of PTSD. 

PMID- 25569080
TI  - Diverse roles of SIRT1 in cancer biology and lipid metabolism.
AB  - SIRT1, an NAD(+)-dependent deacetylase, has been described in the literature as a
      major player in the regulation of cellular stress responses. Its expression has
      been shown to be altered in cancer cells, and it targets both histone and non
      histone proteins for deacetylation and thereby alters metabolic programs in
      response to diverse physiological stress. Interestingly, many of the metabolic
      pathways that are influenced by SIRT1 are also altered in tumor development. Not
      only does SIRT1 have the potential to regulate oncogenic factors, it also
      orchestrates many aspects of metabolism and lipid regulation and recent reports
      are beginning to connect these areas. SIRT1 influences pathways that provide an
      alternative means of deriving energy (such as fatty acid oxidation and
      gluconeogenesis) when a cell encounters nutritive stress, and can therefore lead
      to altered lipid metabolism in various pathophysiological contexts. This review
      helps to show the various connections between SIRT1 and major pathways in
      cellular metabolism and the consequence of SIRT1 deregulation on carcinogenesis
      and lipid metabolism.

PMID- 25569082
TI  - Revealing the supramolecular nature of side-chain terpyridine-functionalized
      polymer networks.
AB  - Nowadays, finely controlling the mechanical properties of polymeric materials is
      possible by incorporating supramolecular motifs into their architecture. In this
      context, the synthesis of a side-chain terpyridine-functionalized poly(2
      (dimethylamino)ethyl methacrylate) is reported via reversible addition
      fragmentation chain transfer polymerization. By addition of transition metal
      ions, concentrated aqueous solutions of this polymer turn into metallo
      supramolecular hydrogels whose dynamic mechanical properties are investigated by
      rotational rheometry. Hence, the possibility for the material to relax mechanical
      constrains via dissociation of transient cross-links is brought into light. In
      addition, the complex phenomena occurring under large oscillatory shear are
      interpreted in the context of transient networks. 

PMID- 25569083
TI  - Elucidating mechanisms of toxicity using phenotypic data from primary human cell
      systems--a chemical biology approach for thrombosis-related side effects.
AB  - Here we describe a chemical biology approach for elucidating potential toxicity
      mechanisms for thrombosis-related side effects. This work takes advantage of a
      large chemical biology data set comprising the effects of known, well
      characterized reference agents on the cell surface levels of tissue factor (TF)
      in a primary human endothelial cell-based model of vascular inflammation, the
      BioMAP(r) 3C system. In previous work with the Environmental Protection Agency
      (EPA) for the ToxCastTM program, aryl hydrocarbon receptor (AhR) agonists and
      estrogen receptor (ER) antagonists were found to share an usual activity, that of
      increasing TF levels in this system. Since human exposure to compounds in both
      chemical classes is associated with increased incidence of thrombosis-related
      side effects, we expanded this analysis with a large number of well-characterized
      reference compounds in order to better understand the underlying mechanisms. As a
      result, mechanisms for increasing (AhR, histamine H1 receptor, histone
      deacetylase or HDAC, hsp90, nuclear factor kappa B or NFkappaB, MEK, oncostatin M
      receptor, Jak kinase, and p38 MAPK) and decreasing (vacuolar ATPase or V-ATPase)
      and mTOR) TF expression levels were uncovered. These data identify the nutrient,
      lipid, bacterial, and hypoxia sensing functions of autophagy as potential key
      regulatory points controlling cell surface TF levels in endothelial cells and
      support the mechanistic hypothesis that these functions are associated with
      thrombosis-related side effects in vivo. 

PMID- 25569084
TI  - Melatonin and female hormone secretion in postmenopausal overweight women.
AB  - Estrogen deficiency is considered to be the main cause of increased appetite and
      increased weight in postmenopausal women. In this period, reduced secretion of
      melatonin (MEL) was also observed. The aim of the study was to evaluate the
      secretion of melatonin, 17-beta estradiol and follicle-stimulating hormone (FSH)
      in relation to body mass index (BMI) in pre- and postmenopausal women. The study
      included 90 women divided into three equal groups: group I (control)-women
      without menstrual disorders, group II-postmenopausal women without change in
      appetite and body weight, group III-postmenopausal women experiencing increased
      appetite and weight gain. In each patient, serum melatonin, 17-beta-estradiol,
      FSH and urine a 6-sulfatoxymelatonin (aMT6s) were determined. Compared to the
      control group, the level of melatonin and estradiol was statistically lower. The
      FSH level was higher than in the groups of postmenopausal women. No significant
      correlation was found in all groups between the level of melatonin and the levels
      of estradiol and FSH. A negative correlation was found between aMT6s excretion
      and BMI, and a positive correlation between the level of FSH and BMI, mainly in
      overweight women. The obtained results indicate a significant effect of melatonin
      deficiency on the process of weight gain in postmenopausal women and justify its
      use in treatment of these disorders. 

PMID- 25569081
TI  - Potential relationship between inadequate response to DNA damage and development
      of myelodysplastic syndrome.
AB  - Hematopoietic stem cells (HSCs) are responsible for the continuous regeneration
      of all types of blood cells, including themselves. To ensure the functional and
      genomic integrity of blood tissue, a network of regulatory pathways tightly
      controls the proliferative status of HSCs. Nevertheless, normal HSC aging is
      associated with a noticeable decline in regenerative potential and possible
      changes in other functions. Myelodysplastic syndrome (MDS) is an age-associated
      hematopoietic malignancy, characterized by abnormal blood cell maturation and a
      high propensity for leukemic transformation. It is furthermore thought to
      originate in a HSC and to be associated with the accrual of multiple genetic and
      epigenetic aberrations. This raises the question whether MDS is, in part, related
      to an inability to adequately cope with DNA damage. Here we discuss the various
      components of the cellular response to DNA damage. For each component, we
      evaluate related studies that may shed light on a potential relationship between
      MDS development and aberrant DNA damage response/repair. 

PMID- 25569085
TI  - Hydrostatic pressure influences HIF-2 alpha expression in chondrocytes.
AB  - Hypoxia-inducible factor (HIF)-2alpha is considered to play a major role in the
      progression of osteoarthritis. Recently, it was reported that pressure amplitude
      influences HIF-2alpha expression in murine endothelial cells. We examined whether
      hydrostatic pressure is involved in expression of HIF-2alpha in articular
      chondrocytes. Chondrocytes were cultured and stimulated by inflammation or
      hydrostatic pressure of 0, 5, 10, or 50 MPa. After stimulation, heat shock
      protein (HSP) 70, HIF-2alpha, nuclear factor kappa B (NF-kappaB), matrix
      metalloproteinase (MMP)-13, MMP-3, and vascular endothelial growth factor (VEGF)
      gene expression were evaluated. The levels of all gene expression were increased
      by inflammatory stress. When chondrocytes were exposed to a hydrostatic pressure
      of 5 MPa, HIF-2alpha, MMP-13, and MMP-3 gene expression increased significantly
      although those of HSP70 and NF-kappaB were not significantly different from the
      control group. In contrast, HIF-2alpha gene expression did not increase under a
      hydrostatic pressure of 50 MPa although HSP70 and NF-kappaB expression increased
      significantly compared to control. We considered that hydrostatic pressure of 5
      MPa could regulate HIF-2alpha independent of NF-kappaB, because the level of HIF
      2alpha gene expression increased significantly without upregulation of NF-kappaB
      expression at 5 MPa. Hydrostatic pressure may influence cartilage degeneration,
      inducing MMP-13 and MMP-3 expression through HIF-2alpha. 

PMID- 25569086
TI  - Hypermethylation of the 16q23.1 tumor suppressor gene ADAMTS18 in clear cell
      renal cell carcinoma.
AB  - To identify tumor suppressor genes (TSGs) silenced by hypermethylation and
      discover new epigenetic biomarkers for early cancer detection. ADAMTS18, located
      at 16q23.1, has been reported to be a critical TSG in multiple primary tumors;
      however, this has not yet been verified in clear cell renal cell carcinoma
      (ccRCC). We explored epigenetic alterations in this gene in ccRCC and analyzed
      possible clinicopathological associations. We examined ADAMTS18 gene expression
      and methylation by semi-quantitative reverse transcription PCR (RT-PCR) and
      methylation-specific polymerase chain reaction (MSP) in 5 ccRCC-derived cell
      lines before and after treatment with 5-aza-2'-deoxycytidine (5-AzaC). MSP was
      further performed for 101 ccRCC primary tumors and 20 adjacent normal tissues.
      Some cell lines and specimens were examined by subsequent bisulfite genomic
      sequencing (BGS) and real-time PCR. Further, we analyzed the relationship between
      the ADAMTS18 gene methylation and clinicopathological features, including short
      term disease-free survival (DFS), in patients with ccRCC. ADAMTS18 down
      regulation and hypermethylation were detected in the ccRCC-derived cell lines
      using RT-PCR and MSP. Treatment with 5-AzaC reversed the hypermethylation of the
      ADAMTS18 gene and restored its expression. Hypermethylation was further detected
      in 44 of 101 (43.6%) primary tumors and 3 of 20 (15.0%) adjacent normal tissues.
      However, a significant difference between both groups was observed (p = 0.02).
      BGS analysis and real-time PCR were subsequently performed to confirm the results
      of RT-PCR and MSP. Furthermore, the methylation status of ADAMTS18 was not
      significantly associated with gender, age, location, tumor diameter, pathological
      stage, nuclear grade or short-term DFS in patients with ccRCC (p > 0.05). The
      ADAMTS18 gene is often down-regulated by hypermethylation in ccRCC-derived cell
      lines and primary tumors, indicating its critical role as a TSG in ccRCC. We
      conclude that ADAMTS18 gene hypermethylation may be involved in the tumorigenesis
      of ccRCC and may serve as a novel biomarker for this disease. 

PMID- 25569088
TI  - Cloud computing-based TagSNP selection algorithm for human genome data.
AB  - Single nucleotide polymorphisms (SNPs) play a fundamental role in human genetic
      variation and are used in medical diagnostics, phylogeny construction, and drug
      design. They provide the highest-resolution genetic fingerprint for identifying
      disease associations and human features. Haplotypes are regions of linked genetic
      variants that are closely spaced on the genome and tend to be inherited together.
      Genetics research has revealed SNPs within certain haplotype blocks that
      introduce few distinct common haplotypes into most of the population. Haplotype
      block structures are used in association-based methods to map disease genes. In
      this paper, we propose an efficient algorithm for identifying haplotype blocks in
      the genome. In chromosomal haplotype data retrieved from the HapMap project
      website, the proposed algorithm identified longer haplotype blocks than an
      existing algorithm. To enhance its performance, we extended the proposed
      algorithm into a parallel algorithm that copies data in parallel via the Hadoop
      MapReduce framework. The proposed MapReduce-paralleled combinatorial algorithm
      performed well on real-world data obtained from the HapMap dataset; the
      improvement in computational efficiency was proportional to the number of
      processors used. 

PMID- 25569090
TI  - Pulicaria glutinosa extract: a toolbox to synthesize highly reduced graphene
      oxide-silver nanocomposites.
AB  - A green, one-step approach for the preparation of graphene/Ag nanocomposites (PE
      HRG-Ag) via simultaneous reduction of both graphene oxide (GRO) and silver ions
      using Pulicaria glutinosa plant extract (PE) as reducing agent is reported. The
      plant extract functionalizes the surfaces of highly reduced graphene oxide (HRG)
      which helps in conjugating the Ag NPs to HRG. Increasing amounts of Ag precursor
      enhanced the density of Ag nanoparticles (NPs) on HRG. The preparation of PE-HRG
      Ag nanocomposite is monitored by using ultraviolet-visible (UV-Vis) spectroscopy,
      powder X-ray diffraction (XRD), and energy dispersive X-ray (EDX). The as
      prepared PE-HRG-Ag nanocomposities display excellent surface-enhanced Raman
      scattering (SERS) activity, and significantly increased the intensities of the
      Raman signal of graphene. 

PMID- 25569089
TI  - Agomelatine beyond borders: current evidences of its efficacy in disorders other
      than major depression.
AB  - Agomelatine, a melatonergic antidepressant with a rapid onset of action, is one
      of the most recent drugs in the antidepressant category. Agomelatine's
      antidepressant actions are attributed to its sleep-promoting and chronobiotic
      actions mediated by MT1 and MT2 receptors present in the suprachiasmatic nucleus,
      as well as to its effects on the blockade of 5-HT2c receptors. Blockade of 5-HT2c
      receptors causes release of both noradrenaline and dopamine at the fronto
      cortical dopaminergic and noradrenergic pathways. The combined actions of
      agomelatine on MT1/MT2 and 5-HT2c receptors facilitate the resynchronization of
      altered circadian rhythms and abnormal sleep patterns. Agomelatine appeared to be
      effective in treating major depression. Moreover, evidence exists that points out
      a possible efficacy of such drug in the treatment of bipolar depression, anxiety
      disorders, alcohol dependence, migraines etc. Thus, the aim of this narrative
      review was to elucidate current evidences on the role of agomelatine in disorders
      other than major depression. 

PMID- 25569087
TI  - Ca2+-dependent regulations and signaling in skeletal muscle: from electro
      mechanical coupling to adaptation.
AB  - Calcium (Ca2+) plays a pivotal role in almost all cellular processes and ensures
      the functionality of an organism. In skeletal muscle fibers, Ca(2+) is critically
      involved in the innervation of skeletal muscle fibers that results in the
      exertion of an action potential along the muscle fiber membrane, the prerequisite
      for skeletal muscle contraction. Furthermore and among others, Ca(2+) regulates
      also intracellular processes, such as myosin-actin cross bridging, protein
      synthesis, protein degradation and fiber type shifting by the control of Ca(2+)
      sensitive proteases and transcription factors, as well as mitochondrial
      adaptations, plasticity and respiration. These data highlight the overwhelming
      significance of Ca(2+) ions for the integrity of skeletal muscle tissue. In this
      review, we address the major functions of Ca(2+) ions in adult muscle but also
      highlight recent findings of critical Ca(2+)-dependent mechanisms essential for
      skeletal muscle-regulation and maintenance.

PMID- 25569091
TI  - Factor XIII B subunit polymorphisms and the risk of coronary artery disease.
AB  - The aim of the case-control study was to explore the effect of coagulation factor
      XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery
      disease, and on FXIII levels. In the study, 687 patients admitted for coronary
      angiography to investigate suspected coronary artery disease and 994 individuals
      representing the Hungarian population were enrolled. The patients were classified
      according to the presence of significant coronary atherosclerosis (CAS) and
      history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg
      and for intron K nt29756 C>G polymorphisms; the latter results in the replacement
      of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism
      did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele
      provided significant protection against CAS and MI in patients with a fibrinogen
      level in the upper tertile. However, this effect prevailed only in the presence
      of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was
      revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII
      levels, and FXIII levels in the lower tertile provided significant protection
      against MI. It is suggested that the protective effect of the combined
      polymorphisms is related to decreased FXIII levels. 

PMID- 25569092
TI  - Excited States and photodebromination of selected polybrominated diphenyl ethers:
      computational and quantitative structure--property relationship studies.
AB  - This paper presents a density functional theory (DFT)/time-dependent DFT (TD-DFT)
      study on the lowest lying singlet and triplet excited states of 20 selected
      polybrominateddiphenyl ether (PBDE) congeners, with the solvation effect included
      in the calculations using the polarized continuum model (PCM). The results
      obtained showed that for most of the brominated diphenyl ether (BDE) congeners,
      the lowest singlet excited state was initiated by the electron transfer from HOMO
      to LUMO, involving a pi-sigma* excitation. In triplet excited states, structure
      of the BDE congeners differed notably from that of the BDE ground states with one
      of the specific C-Br bonds bending off the aromatic plane. In addition, the
      partial least squares regression (PLSR), principal component analysis-multiple
      linear regression analysis (PCA-MLR), and back propagation artificial neural
      network (BP-ANN) approaches were employed for a quantitative structure-property
      relationship (QSPR) study. Based on the previously reported kinetic data for the
      debromination by ultraviolet (UV) and sunlight, obtained QSPR models exhibited a
      reasonable evaluation of the photodebromination reactivity even when the BDE
      congeners had same degree of bromination, albeit different patterns of
      bromination. 

PMID- 25569093
TI  - Trans-splicing improvement by the combined application of antisense strategies.
AB  - Spliceosome-mediated RNA trans-splicing has become an emergent tool for the
      repair of mutated pre-mRNAs in the treatment of genetic diseases. RNA trans
      splicing molecules (RTMs) are designed to induce a specific trans-splicing
      reaction via a binding domain for a respective target pre-mRNA region. A
      previously established reporter-based screening system allows us to analyze the
      impact of various factors on the RTM trans-splicing efficiency in vitro. Using
      this system, we are further able to investigate the potential of antisense RNAs
      (AS RNAs), presuming to improve the trans-splicing efficiency of a selected RTM,
      specific for intron 102 of COL7A1. Mutations in the COL7A1 gene underlie the
      dystrophic subtype of the skin blistering disease epidermolysis bullosa (DEB). We
      have shown that co-transfections of the RTM and a selected AS RNA, interfering
      with competitive splicing elements on a COL7A1-minigene (COL7A1-MG), lead to a
      significant increase of the RNA trans-splicing efficiency. Thereby, accurate
      trans-splicing between the RTM and the COL7A1-MG is represented by the
      restoration of full-length green fluorescent protein GFP on mRNA and protein
      level. This mechanism can be crucial for the improvement of an RTM-mediated
      correction, especially in cases where a high trans-splicing efficiency is
      required. 

PMID- 25569094
TI  - Telomerase reverse transcriptase regulates microRNAs.
AB  - MicroRNAs are small non-coding RNAs that inhibit the translation of target mRNAs.
      In humans, most microRNAs are transcribed by RNA polymerase II as long primary
      transcripts and processed by sequential cleavage of the two RNase III enzymes,
      DROSHA and DICER, into precursor and mature microRNAs, respectively. Although the
      fundamental functions of microRNAs in RNA silencing have been gradually
      uncovered, less is known about the regulatory mechanisms of microRNA expression.
      Here, we report that telomerase reverse transcriptase (TERT) extensively affects
      the expression levels of mature microRNAs. Deep sequencing-based screens of short
      RNA populations revealed that the suppression of TERT resulted in the
      downregulation of microRNAs expressed in THP-1 cells and HeLa cells. Primary and
      precursor microRNA levels were also reduced under the suppression of TERT.
      Similar results were obtained with the suppression of either BRG1 (also called
      SMARCA4) or nucleostemin, which are proteins interacting with TERT and
      functioning beyond telomeres. These results suggest that TERT regulates microRNAs
      at the very early phases in their biogenesis, presumably through non-telomerase
      mechanism(s). 

PMID- 25569096
TI  - Human adipose tissue conditioned media from lean subjects is protective against
      H2O2 induced neurotoxicity in human SH-SY5Y neuronal cells.
AB  - Adipose tissue secretes numerous hormone-like factors, which are known as
      adipokines. Adipokine receptors have been identified in the central nervous
      system but the potential role of adipokine signaling in neuroprotection is
      unclear. The aim of this study is to determine (1) Whether adipokines secreted
      from cultured adipose tissue of lean humans is protective against oxidative
      stress-induced neurotoxicity in human SH-SY5Y neuronal cells; and (2) To explore
      potential signaling pathways involved in these processes. Adipose tissue
      conditioned media (ATCM) from healthy lean subjects completely prevented H2O2
      induced neurotoxicity, while this effect is lost after heating ATCM. ATCM
      activated the phosphorylation of ERK1/2, JNK and Akt at serine 308 in SH-SY5Y
      cells. PD98059 (25 uM), SP600125 (5 uM) and LY29400 (20 uM) partially blocked the
      protective effects of ATCM against H2O2 induced neurotoxicity. Findings
      demonstrate that heat-sensitive factors secreted from human adipose tissue of
      lean subjects are protective against H2O2 induced neurotoxicity and ERK1/2, JNK,
      and PI3K signaling pathways are involved in these processes. In conclusion, this
      study demonstrates preliminary but encouraging data to further support that
      adipose tissue secreted factors from lean human subjects might possess
      neuroprotective properties and unravel the specific roles of ERK1/2, JNK and PI3K
      in these processes. 

PMID- 25569098
TI  - Premature collagen fibril formation, fibroblast-mast cell interactions and mast
      cell-mediated phagocytosis of collagen in keloids.
AB  - Keloids are benign hyper-proliferative growths of fibrous tissue where increased
      fibroblast activity results in abnormal collagen deposition. Excessive
      inflammation is a characteristic feature of keloids, but little is known about
      the underlying ultrastructural features of keloids related to collagen
      processing, fibril and fiber formation, the interaction between fibroblasts and
      associated collagen fibers and mast cells. In this study, the ultrastructure of
      the dermis of keloid patients was evaluated using light and transmission electron
      microscopy techniques. Abnormal intracellular premature collagen fibril formation
      was observed. Phagocytosis of collagen fibrils by mast cells was a common
      ultrastructural feature of keloid tissue as was a close or direct association
      between fibroblasts and mast cells. Based on these findings and recent advances
      in knowledge related to collagen synthesis, fibril formation and processing, we
      hypothesize that keloid formation is primarily due to abnormal collagen synthesis
      where the consequent accumulation of collagen fibers causes increased mast cell
      recruitment and collagen phagocytosis. Subsequent release of mast cell-derived
      mediators then promotes further collagen synthesis. The observation of early
      formation in keloid tissue of premature insoluble collagen fibrils supports
      previous studies that enzymes such as procollagen C-proteinase are important
      early therapeutic targets. 

PMID- 25569095
TI  - Analgesic, anxiolytic and anaesthetic effects of melatonin: new potential uses in
      pediatrics.
AB  - Exogenous melatonin is used in a number of situations, first and foremost in the
      treatment of sleep disorders and jet leg. However, the hypnotic, antinociceptive,
      and anticonvulsant properties of melatonin endow this neurohormone with the
      profile of a drug that modulates effects of anesthetic agents, supporting its
      potential use at different stages during anesthetic procedures, in both adults
      and children. In light of these properties, melatonin has been administered to
      children undergoing diagnostic procedures requiring sedation or general
      anesthesia, such as magnetic resonance imaging, auditory brainstem response tests
      and electroencephalogram. Controversial data support the use of melatonin as
      anxiolytic and antinociceptive agents in pediatric patients undergoing surgery.
      The aim of this review was to evaluate available evidence relating to efficacy
      and safety of melatonin as an analgesic and as a sedative agent in children.
      Melatonin and its analogs may have a role in antinociceptive therapies and as an
      alternative to midazolam in premedication of adults and children, although its
      effectiveness is still controversial and available data are clearly incomplete. 

PMID- 25569097
TI  - Anti-inflammatory and analgesic effects of pyeongwisan on LPS-stimulated murine
      macrophages and mouse models of acetic acid-induced writhing response and xylene
      induced ear edema.
AB  - Pyeongwisan (PW) is an herbal medication used in traditional East Asian medicine
      to treat anorexia, abdominal distension, borborygmus and diarrhea caused by
      gastric catarrh, atony and dilatation. However, its effects on inflammation
      related diseases are unknown. In this study, we investigated the biological
      effects of PW on lipopolysaccharide (LPS)-mediated inflammation in macrophages
      and on local inflammation in vivo. We investigated the biological effects of PW
      on the production of inflammatory mediators, pro-inflammatory cytokines and
      related products as well as the activation of nuclear factor kappa B (NF-kappaB)
      and mitogen-activated protein kinases (MAPKs) in LPS-stimulated macrophages.
      Additionally, we evaluated the analgesic effect on the acetic acid-induced
      writhing response and the inhibitory activity on xylene-induced ear edema in
      mice. PW showed anti-inflammatory effects by inhibiting the production of nitric
      oxide (NO), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and
      interleukin-1beta (IL-1beta). In addition, PW strongly suppressed inducible
      nitric oxide synthase (iNOS), a NO synthesis enzyme, induced heme oxygenase-1 (HO
      1) expression and inhibited NF-kappaB activation and MAPK phosphorylation. Also,
      PW suppressed TNF-alpha, IL-6 and IL-1beta cytokine production in LPS-stimulated
      peritoneal macrophage cells. Furthermore, PW showed an analgesic effect on the
      writhing response and an inhibitory effect on mice ear edema. We demonstrated the
      anti-inflammatory effects and inhibitory mechanism in macrophages as well as
      inhibitory activity of PW in vivo for the first time. Our results suggest the
      potential value of PW as an inflammatory therapeutic agent developed from a
      natural substance. 

PMID- 25569099
TI  - Disrupted autophagy after spinal cord injury is associated with ER stress and
      neuronal cell death.
AB  - Autophagy is a catabolic mechanism facilitating degradation of cytoplasmic
      proteins and organelles in a lysosome-dependent manner. Autophagy flux is
      necessary for normal neuronal homeostasis and its dysfunction contributes to
      neuronal cell death in several neurodegenerative diseases. Elevated autophagy has
      been reported after spinal cord injury (SCI); however, its mechanism, cell type
      specificity and relationship to cell death are unknown. Using a rat model of
      contusive SCI, we observed accumulation of LC3-II-positive autophagosomes
      starting at posttrauma day 1. This was accompanied by a pronounced accumulation
      of autophagy substrate protein p62, indicating that early elevation of autophagy
      markers reflected disrupted autophagosome degradation. Levels of lysosomal
      protease cathepsin D and numbers of cathepsin-D-positive lysosomes were also
      decreased at this time, suggesting that lysosomal damage may contribute to the
      observed defect in autophagy flux. Normalization of p62 levels started by day 7
      after SCI, and was associated with increased cathepsin D levels. At day 1 after
      SCI, accumulation of autophagosomes was pronounced in ventral horn motor neurons
      and dorsal column oligodendrocytes and microglia. In motor neurons, disruption of
      autophagy strongly correlated with evidence of endoplasmic reticulum (ER) stress.
      As autophagy is thought to protect against ER stress, its disruption after SCI
      could contribute to ER-stress-induced neuronal apoptosis. Consistently, motor
      neurons showing disrupted autophagy co-expressed ER-stress-associated initiator
      caspase 12 and cleaved executioner caspase 3. Together, these findings indicate
      that SCI causes lysosomal dysfunction that contributes to autophagy disruption
      and associated ER-stress-induced neuronal apoptosis. 

PMID- 25569100
TI  - Long non-coding RNA CCAT1 promotes gallbladder cancer development via negative
      modulation of miRNA-218-5p.
AB  - Protein-coding genes account for only ~2% of the human genome, whereas the vast
      majority of transcripts are non-coding RNAs (ncRNAs) including long ncRNAs
      (lncRNAs). A growing volume of literature has proposed that lncRNAs are important
      factors in cancer. Colon cancer-associated transcript-1 (CCAT1), an lncRNA, which
      was first identified in colon cancer, was previously shown to promote tumor
      development and be a negative prognostic factor in gastric cancer. However, the
      mechanism through which CCAT1 exerts its oncogenic activity remains largely
      unknown. Recently, a novel regulatory mechanism has been proposed in which RNAs
      can cross-talk with each other via competing shared for microRNAs (miRNAs). The
      proposed competitive endogenous RNAs could mediate the bioavailability of miRNAs
      on their targets, thus imposing another level of posttranscriptional regulation.
      In this study, we demonstrated that CCAT1 was upregulated in gallbladder cancer
      (GBC) tissues. CCAT1 silencing downregulated, whereas CCAT1 overexpression
      enhanced the expression of miRNA-218-5p target gene Bmi1 through competitively
      'spongeing' miRNA-218-5p. Our data revealed that CCAT1 knockdown impaired the
      proliferation and invasiveness of GBC cells, at least in part through affecting
      miRNA-218-5p-mediated regulation of Bmi1. Moreover, CCAT1 transcript level was
      correlated with Bmi1 mRNA level in GBC tissues. Together, these results suggest
      that CCAT1 is a driver of malignancy, which acts in part through 'spongeing'
      miRNA-218-5p. 

PMID- 25569101
TI  - Candidate tumor suppressor B-cell translocation gene 3 impedes neoplastic
      progression by suppression of AKT.
AB  - BTG3 (B-cell translocation gene 3) is a p53 target that also binds and inhibits
      E2F1. Although it connects two major growth-regulatory pathways functionally and
      is downregulated in human cancers, whether and how BTG3 acts as a tumor
      suppressor remain largely uncharacterized. Here we present evidence that BTG3
      binds and suppresses AKT, a kinase frequently deregulated in cancers. BTG3
      ablation results in increased AKT activity that phosphorylates and inhibits
      glycogen synthase kinase 3beta. Consequently, we also observed elevated beta
      catenin/T-cell factor activity, upregulation of mesenchymal markers, and enhanced
      cell migration. Consistent with these findings, BTG3 overexpression suppressed
      tumor growth in mouse xenografts, and was associated with diminished AKT
      phosphorylation and reduced beta-catenin in tissue specimens. Significantly, a
      short BTG3-derived peptide was identified, which recapitulates these effects in
      vitro and in cells. Thus, our study provides mechanistic insights into a
      previously unreported AKT inhibitory pathway downstream of p53. The
      identification of an AKT inhibitory peptide also unveils a new avenue for cancer
      therapeutics development. 

PMID- 25569102
TI  - Primary clear cell renal carcinoma cells display minimal mitochondrial
      respiratory capacity resulting in pronounced sensitivity to glycolytic inhibition
      by 3-Bromopyruvate.
AB  - Changes of cellular metabolism are an integral property of the malignant
      potential of most cancer cells. Already in the 1930s, Otto Warburg observed that
      tumor cells preferably utilize glycolysis and lactate fermentation for energy
      production, rather than the mitochondrial oxidative phosphorylation dominating in
      normal cells, a phenomenon today known as the Warburg effect. Even though many
      tumor types display a high degree of aerobic glycolysis, they still retain the
      activity of other energy-producing metabolic pathways. One exception seems to be
      the clear cell variant of renal cell carcinoma, ccRCC, where the activity of most
      other pathways than that of glycolysis has been shown to be reduced. This makes
      ccRCC a promising candidate for the use of glycolytic inhibitors in treatment of
      the disease. However, few studies have so far addressed this issue. In this
      report, we show a strikingly reduced mitochondrial respiratory capacity of
      primary human ccRCC cells, resulting in enhanced sensitivity to glycolytic
      inhibition by 3-Bromopyruvate (3BrPA). This effect was largely absent in
      established ccRCC cell lines, a finding that highlights the importance of using
      biologically relevant models in the search for new candidate cancer therapies.
      3BrPA markedly reduced ATP production in primary ccRCC cells, followed by cell
      death. Our data suggest that glycolytic inhibitors such as 3BrPA, that has been
      shown to be well tolerated in vivo, should be further analyzed for the possible
      development of selective treatment strategies for patients with ccRCC. 

PMID- 25569103
TI  - Tamoxifen reduces fat mass by boosting reactive oxygen species.
AB  - As the pandemic of obesity is growing, a variety of animal models have been
      generated to study the mechanisms underlying the increased adiposity and
      development of metabolic disorders. Tamoxifen (Tam) is widely used to activate
      Cre recombinase that spatiotemporally controls target gene expression and
      regulates adiposity in laboratory animals. However, a critical question remains
      as to whether Tam itself affects adiposity and possibly confounds the functional
      study of target genes in adipose tissue. Here we administered Tam to Cre-absent
      forkhead box O1 (FoxO1) floxed mice (f-FoxO1) and insulin receptor substrate
      Irs1/Irs2 double floxed mice (df-Irs) and found that Tam induced approximately
      30% reduction (P<0.05) in fat mass with insignificant change in body weight.
      Mechanistically, Tam promoted reactive oxygen species (ROS) production, apoptosis
      and autophagy, which was associated with downregulation of adipogenic regulator
      peroxisome proliferator-activated receptor gamma and dedifferentiation of mature
      adipocytes. However, normalization of ROS potently suppressed Tam-induced
      apoptosis, autophagy and adipocyte dedifferentiation, suggesting that ROS may
      account, at least in part, for the changes. Importantly, Tam-induced ROS
      production and fat mass reduction lasted for 4-5 weeks in the f-FoxO1 and df-Irs
      mice. Our data suggest that Tam reduces fat mass via boosting ROS, thus making a
      recovery period crucial for posttreatment study. 

PMID- 25569106
TI  - Alcohol cross-coupling for the kinetic resolution of diols via oxidative
      esterification.
AB  - We present an organocatalytic C-O-bond cross-coupling strategy to kinetically
      resolve racemic diols with aromatic and aliphatic alcohols, yielding
      enantioenriched esters. This one-pot protocol utilizes an oligopeptide
      multicatalyst, m-CPBA as the oxidant, and N,N'-diisopropylcarbodiimide as the
      activating agent. Racemic acyclic diols as well as trans-cycloalkane-1,2-diols
      were kinetically resolved, achieving high selectivities and good yields for the
      products and recovered diols. 

PMID- 25569104
TI  - Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated
      necroptosis in L929 cells.
AB  - Endoplasmic reticulum (ER) stress-induced cellular dysfunction and death is
      associated with several human diseases. It has been widely reported that ER
      stress kills through activation of the intrinsic mitochondrial apoptotic pathway.
      Here we demonstrate that ER stress can also induce necroptosis, an receptor
      interacting protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like
      protein (MLKL)-dependent form of necrosis. Remarkably, we observed that
      necroptosis induced by various ER stressors in L929 cells is dependent on tumor
      necrosis factor receptor 1 (TNFR1), but occurs independently of autocrine TNF or
      lymphotoxin alpha production. Moreover, we found that repression of either TNFR1,
      RIPK1 or MLKL did not protect the cells from death but instead allowed a switch
      to ER stress-induced apoptosis. Interestingly, while caspase inhibition was
      sufficient to protect TNFR1- or MLKL-deficient cells from death, rescue of the
      RIPK1-deficient cells additionally required RIPK3 depletion, indicating a switch
      back to RIPK3-dependent necroptosis in caspase-inhibited conditions. The finding
      that ER stress also induces necroptosis may open new therapeutic opportunities
      for the treatment of pathologies resulting from unresolved ER stress. 

PMID- 25569108
TI  - Correlates of cardiovascular disease risk scores in women in Riyadh, Kingdom of
      Saudi Arabia.
AB  - Saudi Arabia has a high prevalence of obesity and physical inactivity. We
      measured cardiovascular (CVD) risk scores and determined the factors associated
      with them in women in Riyadh, Saudi Arabia. A cross-sectional study using a self
      administered questionnaire was conducted on 291 women aged >= 30 years.
      Information was collected on socio-demographics and physical health status.
      Anthropometric and blood pressure measurements were taken. Physical activity was
      measured using Kaiser's Physical Activity Survey and Godin's Leisure Time
      Exercise questionnaire. CVD risk scores were calculated using the non-laboratory
      based Framingham Risk (FRS) prediction model for primary care. FRS scores ranged
      from 0.50 to 21.9. A total of 2.7% (n = 8) of women had a high FRS score (>20),
      5.5% (n = 16) had intermediate scores (11-20), and 91.8% (n = 267) of women had
      low scores (<10) CVD risk scores. Multiple linear regression results indicated
      that a one-unit change in physical activity (household/caregiver index),
      strenuous exercise, waist circumference, number of children, television watching,
      and knee pain were significantly associated with -0.20 (p < .01), -0.12 (p =
      .03), 0.19 (p = .001), 0.29 (p < .01), 0.13 (p = .04), and 0.11 (p = .05) unit
      change in CVD risk scores, respectively. Household activities and strenuous
      exercise had a protective role in females in relation to CVD risk. Programs
      recommending physical activity at all levels should be encouraged.

PMID- 25569109
TI  - Separation and analysis of charged isomers of monoclonal immunoglobulin G by
      ceramic hydroxyapatite chromatography.
AB  - Analysis of monoclonal antibody (MAb) heterogeneity caused by posttranslational
      modifications is important for pharmaceutical quality assurance of antibody
      drugs. In this study, by employing small ceramic hydroxyapatite (HAp) particles
      that were self-manufactured to have a 2.5-um diameter, we attempted to separate
      and analyze MAb isomers. The MAb without N-linked oligosaccharides could be
      separated by 2.5-um HAp chromatography as well as MAb with N-linked
      oligosaccharides. Hence, a variety of N-linked oligosaccharides do not appear to
      be involved in the separation mechanism of HAp chromatography. However, there is
      a difference in retention time between MAb with and without N-linked
      oligosaccharides, meaning that the presence of N-glycan could influence the
      retention time of HAp chromatography. Subsequently, the MAb fractions separated
      by 2.5-um HAp chromatography were analyzed by isoelectric focusing, and seven
      isomers of the MAb having different isoelectric points (pI) were identified. The
      MAb isomers were eluted in order of lower pI isomers with sodium phosphate
      buffer, and enzyme-linked immunosorbent assay indicated the immunoreactivity of
      the fraction including the lowest pI isomers to be remarkably reduced. This study
      yielded details of the separation behavior of HAp chromatography owing to 2.5-um
      HAp particles. 

PMID- 25569105
TI  - A tight control of Rif1 by Oct4 and Smad3 is critical for mouse embryonic stem
      cell stability.
AB  - Prolonged culture of embryonic stem cells (ESCs) leads them to adopt embryonal
      carcinoma cell features, creating enormous dangers for their further application.
      The mechanism involved in ESC stability has not, however, been extensively
      studied. We previously reported that SMAD family member 3 (Smad3) has an
      important role in maintaining mouse ESC stability, as depletion of Smad3 results
      in cancer cell-like properties in ESCs and Smad3-/- ESCs are prone to grow large,
      malignant teratomas. To understand how Smad3 contributes to ESC stability, we
      performed microarray analysis to compare the transcriptome of wild-type and Smad3
      /- ESCs. We found that Rif1 (RAP1-associated protein 1), a factor important for
      genomic stability, is significantly upregulated in Smad3-/- ESCs. The expression
      level of Rif1 needs to be tightly controlled in ESCs, as a low level of Rif1 is
      associated with ESC differentiation, but a high level of Rif1 is linked to ESC
      transformation. In ESCs, Oct4 activates Rif1, whereas Smad3 represses its
      expression. Oct4 recruits Smad3 to bind to Rif1 promoter, but Smad3 joining
      facilitates the loading of a polycomb complex that generates a repressive
      epigenetic modification on Rif1 promoter, and thus maintains the expression of
      Rif1 at a proper level in ESCs. Interestingly, Rif1 short hairpin RNA (shRNA)
      transduced Smad3-/- ESCs showed less malignant properties than the control shRNA
      transduced Smad3-/- ESCs, suggesting a critical role of Rif1 in maintaining the
      stability of ESCs during proliferation. 

PMID- 25569110
TI  - Materials chemistry. Composition-matched molecular "solders" for semiconductors.
AB  - We propose a general strategy to synthesize largely unexplored soluble
      chalcogenidometallates of cadmium, lead, and bismuth. These compounds can be used
      as "solders" for semiconductors widely used in photovoltaics and thermoelectrics.
      The addition of solder helped to bond crystal surfaces and link nano- or
      mesoscale particles together. For example, CdSe nanocrystals with Na2Cd2Se3
      solder was used as a soluble precursor for CdSe films with electron mobilities
      exceeding 300 square centimeters per volt-second. CdTe, PbTe, and Bi2Te3 powders
      were molded into various shapes in the presence of a small additive of
      composition-matched chalcogenidometallate or chalcogel, thus opening new design
      spaces for semiconductor technologies. 

PMID- 25569112
TI  - Atmospheric chemistry. Direct kinetic measurement of the reaction of the simplest
      Criegee intermediate with water vapor.
AB  - Carbonyl oxides, or Criegee intermediates, are important transient species formed
      in the reactions of unsaturated hydrocarbons with ozone. Although direct
      detection of Criegee intermediates has recently been realized, the main
      atmospheric sink of Criegee intermediates remains unclear. We report ultraviolet
      absorption spectroscopic measurements of the lifetime of the simplest Criegee
      intermediate, CH2OO, at various relative humidity levels up to 85% at 298 kelvin.
      An extremely fast decay rate of CH2OO was observed at high humidity. The observed
      quadratic dependence of the decay rate on water concentration implied a
      predominant reaction with water dimer. On the basis of the water dimer
      equilibrium constant, the effective rate coefficient of the CH2OO + (H2O)2
      reaction was determined to be 6.5 (+/-0.8) * 10(-12) cubic centimeters per
      second. This work would help modelers to better constrain the atmospheric
      concentrations of CH2OO. 

PMID- 25569111
TI  - Stem cells. m6A mRNA methylation facilitates resolution of naive pluripotency
      toward differentiation.
AB  - Naive and primed pluripotent states retain distinct molecular properties, yet
      limited knowledge exists on how their state transitions are regulated. Here, we
      identify Mettl3, an N(6)-methyladenosine (m(6)A) transferase, as a regulator for
      terminating murine naive pluripotency. Mettl3 knockout preimplantation epiblasts
      and naive embryonic stem cells are depleted for m(6)A in mRNAs, yet are viable.
      However, they fail to adequately terminate their naive state and, subsequently,
      undergo aberrant and restricted lineage priming at the postimplantation stage,
      which leads to early embryonic lethality. m(6)A predominantly and directly
      reduces mRNA stability, including that of key naive pluripotency-promoting
      transcripts. This study highlights a critical role for an mRNA epigenetic
      modification in vivo and identifies regulatory modules that functionally
      influence naive and primed pluripotency in an opposing manner. 

PMID- 25569114
TI  - Phosphorus in manure and sewage sludge more recyclable than in soluble inorganic
      fertilizer.
AB  - Phosphorus (P) flow from deposits through agriculture to waterways leads to
      eutrophication and depletion of P reserves. Therefore, P must be recycled. Low
      and unpredictable plant availability of P in residues is considered to be a
      limiting factor for recycling. We identified the determinants for the plant
      availability of P in agrifood residues. We quantified P in Italian ryegrass
      (Lolium multiflorum) and in field soil fractions with different plant
      availabilities of P as a response to manure and sewage sludge with a range of P
      capture and hygienization treatments. P was more available in manure and in
      sludge, when it was captured biologically or with a moderate iron (Fe)/P (1.6),
      than in NPK. Increasing rate of sludge impaired P recovery and high Fe/P (9.8)
      prevented it. Anaerobic digestion (AD) reduced plant-availability at relevant
      rates. The recovery of P was increased in AD manure via composting and in AD
      sludge via combined acid and oxidizer. P was not available to plants in the
      sludge hygienized with a high calcium/P. Contrary to assumed knowledge, the
      recyclability of P in appropriately treated residues can be better than in NPK.
      The prevention of P sorption in soil by organic substances in fertilizers
      critically enhances the recyclability of P. 

PMID- 25569115
TI  - Evidence for preferential solvation in the cyclohexane/n-butanol binary solvent
      system.
AB  - We report on the rotational diffusion and vibrational population relaxation
      dynamics of the polycyclic aromatic hydrocarbon (PAH) perylene in a series of
      cyclohexane/n-butanol binary solvent systems. The molecular scale heterogeneity
      of this binary system is seen in both types of data. The rotational diffusion
      results show that in neat n-butanol and neat cyclohexane perylene reorients as an
      oblate rotor, but for all binary solvent systems examined this chromophore
      reorients as a prolate rotor. The perylene ring breathing mode is nearly
      degenerate with the n-butanol terminal methyl group rocking mode and vibrational
      population relaxation data for the perylene ring breathing mode reveal a
      substantial decrease in the relaxation time constant with the addition of small
      amounts of n-butanol to cyclohexane. This finding, in concert with the rotational
      diffusion data, indicates that perylene is solvated preferentially by n-butanol
      in cyclohexane/n-butanol binary solvent systems. The implication of this finding
      is that the cyclohexane/n-butanol binary solvent mixture is not homogeneous on
      nanometer length scales. 

PMID- 25569116
TI  - Light-induced extracellular electron transport by the marine raphidophyte
      Chattonella marina.
AB  - There is increasing interest in extracellular electron transfer (EET) from
      organisms to receptors, particularly in anaerobic biofilms at mineral surfaces.
      Less attention has been given to EET by planktonic organisms in oxic environments
      where extracellular electron generation and transport might be expected to be of
      limited consequence. In this study, the EET activity of the photosynthetic marine
      raphidophyte, Chattonella marina, was examined using a mediatorless
      photosynthetic microbial fuel cell with results showing positive light response.
      Electron output by organisms present in cell suspension was substantially higher
      than those present in biofilms at the electrode surface. Indeed, current
      generation under light illumination of the C. marina suspension continued even
      when contact between the organisms and the electrodes was prevented by dialysis
      membrane, suggesting that soluble electron carriers secreted by C. marina were
      facilitating the EET process. Cyclic voltammetry measurements of the cell-free
      exudate showed redox peaks in the range of 0.1-0.5 V (vs Ag/AgCl), confirming
      that redox active species were present in the cell suspension. Facilitation of
      electron transfer from the planktonic organism to the anode by endogenous redox
      active exudates appears to be critical to current generation. The ability of
      these exudates to remain in their reduced state in the presence of oxygen is
      possibly a function of the spin-restricted nature of oxygen-mediated exudate
      oxidation. Quantification of the EET processes operating in this planktonic
      system assists in understanding the means and extent to which C. marina induces
      redox transformations in the external medium with these transformations
      presumably of benefit to the survival of this organism, potentially including
      facilitation of iron uptake and induction of toxicity to other organisms.

PMID- 25569113
TI  - Tenascin-C: Exploitation and collateral damage in cancer management.
AB  - Despite an increasing knowledge about the causes of cancer, this disease is
      difficult to cure and still causes far too high a death rate. Based on advances
      in our understanding of disease pathogenesis, novel treatment concepts, including
      targeting the tumor microenvironment, have been developed and are being combined
      with established treatment regimens such as surgical removal and radiotherapy.
      Yet it is obvious that we need additional strategies to prevent tumor relapse and
      metastasis. Given its exceptional high expression in most cancers with low
      abundance in normal tissues, tenascin-C appears an ideal candidate for tumor
      treatment. Here, we will summarize the current applications of targeting tenascin
      C as a treatment for different tumors, and highlight the potential of this
      therapeutic approach.

PMID- 25569117
TI  - NHS will not pay for drugs that offer little clinical benefit, says cancer fund
      boss.

PMID- 25569119
TI  - Small molecule discoidin domain receptor kinase inhibitors and potential medical
      applications.
AB  - Discoidin domain receptors (DDRs) are members of the transmembrane receptor
      tyrosine kinase (RTK) superfamily which are distinguished from others by the
      presence of a discoidin motif in the extracellular domain and their utilization
      of collagens as internal ligands. Two types of DDRs, DDR1 and DDR2, have been
      identified with distinct expression profiles and ligand specificities. These DDRs
      play important roles in the regulation of fundamental cellular process, such as
      proliferation, survival, differentiation, adhesion, and matrix remodeling. They
      have also been closely linked to a number of human diseases, including various
      fibrotic disorders, atherosclerosis, and cancer. As a consequence, DDRs have been
      considered as novel potential molecular targets for drug discovery and increasing
      efforts are being devoted to the identification of new small molecule inhibitors
      targeting the receptors. In this review, we offer a contemporary overview on the
      discovery of DDRs inhibitors and their potential medical application for the
      treatment of cancer and inflammation related disorders. 

PMID- 25569121
TI  - Effect of culture conditions on the resistance of Pseudomonas aeruginosa biofilms
      to disinfecting agents.
AB  - The relationship between the environmental conditions of biofilm formation and
      resistance to disinfectants was studied. Anti-biofilm assays were performed
      against biofilms grown at 20, 30 and 37 degrees C on stainless steel and
      polycarbonate, over 24 and 48 h. A rise in growth temperature increased the
      resistance of 24 h biofilms to disinfectants containing didecyldimethylammonium
      chloride and decreased it to a disinfectant containing
      alkyldimethylbenzylammonium chloride. The increase in growth temperature coupled
      with an incubation time of 24 h promoted increases in both matrix production and
      the membrane rigidity of sessile cells. An increase in incubation time also
      increased both matrix production and the membrane rigidity of sessile cells. Such
      phenomena resulted in an increased resistance to disinfectants of biofilms grown
      at 20 and 30 degrees C. The resistance of 48 h biofilms to disinfectants
      decreased with an increase in growth temperature despite the increase in matrix
      production and the membrane rigidity of sessile cells.

PMID- 25569118
TI  - Stimulation of Respiratory Motor Output and Ventilation in a Murine Model of
      Pompe Disease by Ampakines.
AB  - Pompe disease results from a mutation in the acid alpha-glucosidase gene leading
      to lysosomal glycogen accumulation. Respiratory insufficiency is common, and the
      current U.S. Food and Drug Administration-approved treatment, enzyme replacement,
      has limited effectiveness. Ampakines are drugs that enhance alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionic acid receptor responses and can increase
      respiratory motor drive. Recent work indicates that respiratory motor drive can
      be blunted in Pompe disease, and thus pharmacologic stimulation of breathing may
      be beneficial. Using a murine Pompe model with the most severe clinical genotype
      (the Gaa(-/-) mouse), our primary objective was to test the hypothesis that
      ampakines can stimulate respiratory motor output and increase ventilation. Our
      second objective was to confirm that neuropathology was present in Pompe mouse
      medullary respiratory control neurons. The impact of ampakine CX717 on breathing
      was determined via phrenic and hypoglossal nerve recordings in anesthetized mice
      and whole-body plethysmography in unanesthetized mice. The medulla was examined
      using standard histological methods coupled with immunochemical markers of
      respiratory control neurons. Ampakine CX717 robustly increased phrenic and
      hypoglossal inspiratory bursting and reduced respiratory cycle variability in
      anesthetized Pompe mice, and it increased inspiratory tidal volume in
      unanesthetized Pompe mice. CX717 did not significantly alter these variables in
      wild-type mice. Medullary respiratory neurons showed extensive histopathology in
      Pompe mice. Ampakines stimulate respiratory neuromotor output and ventilation in
      Pompe mice, and therefore they have potential as an adjunctive therapy in Pompe
      disease. 

PMID- 25569120
TI  - Transparent reporting of a multivariable prediction model for individual
      prognosis or diagnosis (TRIPOD): the TRIPOD statement.
AB  - Prediction models are developed to aid health care providers in estimating the
      probability or risk that a specific disease or condition is present (diagnostic
      models) or that a specific event will occur in the future (prognostic models), to
      inform their decision making. However, the overwhelming evidence shows that the
      quality of reporting of prediction model studies is poor. Only with full and
      clear reporting of information on all aspects of a prediction model can risk of
      bias and potential usefulness of prediction models be adequately assessed. The
      Transparent Reporting of a multivariable prediction model for Individual
      Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for
      the reporting of studies developing, validating, or updating a prediction model,
      whether for diagnostic or prognostic purposes. This article describes how the
      TRIPOD Statement was developed. An extensive list of items based on a review of
      the literature was created, which was reduced after a Web based survey and
      revised during a three day meeting in June 2011 with methodologists, health care
      professionals, and journal editors. The list was refined during several meetings
      of the steering group and in e-mail discussions with the wider group of TRIPOD
      contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed
      essential for transparent reporting of a prediction model study. The TRIPOD
      Statement aims to improve the transparency of the reporting of a prediction model
      study regardless of the study methods used. The TRIPOD Statement is best used in
      conjunction with the TRIPOD explanation and elaboration document. To aid the
      editorial process and readers of prediction model studies, it is recommended that
      authors include a completed checklist in their submission (also available at
      www.tripod-statement.org).To encourage dissemination of the TRIPOD Statement,
      this article is freely accessible on the Annals of Internal Medicine Web site
      (www.annals.org) and will be also published in BJOG, British Journal of Cancer,
      British Journal of Surgery, BMC Medicine, The BMJ, Circulation, Diabetic
      Medicine, European Journal of Clinical Investigation, European Urology, and
      Journal of Clinical Epidemiology. The authors jointly hold the copyright of this
      article. An accompanying explanation and elaboration article is freely available
      only on www.annals.org; Annals of Internal Medicine holds copyright for that
      article. 

PMID- 25569122
TI  - Nontargeted metabolite profiles and sensory properties of strawberry cultivars
      grown both organically and conventionally.
AB  - Strawberry (Fragaria * ananassa Duch.) contains many secondary metabolites
      potentially beneficial for human health, and several of these compounds
      contribute to strawberry sensory properties, as well. In this study, three
      strawberry cultivars grown both conventionally and organically were subjected to
      nontargeted metabolite profiling analysis with LC-qTOF-ESI-MS and to descriptive
      sensory evaluation by a trained panel. Combined metabolome and sensory data (PLS
      model) revealed that 79% variation in the metabolome explained 88% variation in
      the sensory profiles. Flavonoids and condensed and hydrolyzable tannins
      determined the orosensory properties, and fatty acids contributed to the odor
      attributes of strawberry. Overall, the results indicated that the chemical
      composition and sensory quality of strawberries grown in different cultivation
      systems vary mostly according to cultivar. Organic farming practices may enhance
      the accumulation of some plant metabolites in specific strawberry genotypes.
      Careful cultivar selection is a key factor for the improvement of nutritional
      quality and marketing value of organic strawberries. 

PMID- 25569123
TI  - Local and sustained gene delivery in silica-collagen nanocomposites.
AB  - Local delivery of biomolecules from hydrogels is highly challenging because of
      their rapid diffusion and degradation. Gene therapy represents an alternative
      that allows for the prolonged production of proteins by transfected cells. In
      this study, we have developed nanocomposites consisting of DNA-polyethylenimine
      silica nanoparticle complexes coencapsulated with fibroblasts within collagen
      hydrogels. Through the modulation of the particle size and polyethylenimine
      molecular weight, it was possible to achieve "in-gel" transfection permitting the
      sustained production of biomolecules from hydrogels over 1 week. Alternative
      configurations consisting of particle addition to cellularized gels and cell
      culture in the presence of complex-containing hydrogels were also investigated.
      These studies demonstrated that particle encapsulation limits DNA and silica
      dissemination outside the collagen hydrogels. They also show the key role of cell
      proliferation within collagen hydrogels on the transfection efficiency. Such
      nanocomposites therefore constitute promising materials for the development of
      novel gene delivery systems to promote tissue repair. 

PMID- 25569124
TI  - Resveratrol Attenuates Oxidative Stress and Extends Life Span in the Annual Fish
      Nothobranchius guentheri.
AB  - Resveratrol is a natural polyphenol derived mainly from the skin of grapes and
      from red wine. Resveratrol prolongs life span in several invertebrates, but this
      function is not found in mice. Our recently published paper demonstrated that
      resveratrol prolonged longevity of the annual fish Nothobranchius guentheri, a
      promising vertebrate model for anti-aging research. However, the anti-aging
      process by resveratrol remains largely unexplored, and little is known about its
      effects on oxidative stress. In this study, by long-term supplementation of
      resveratrol from sexual maturity onward in the annual fish, we detected
      survivorship and oxidative stress at three different developmental stages in
      vivo. A total of 112 fish were fed with resveratrol in the concentration of 200
      MUg/gram food and 111 fish without resveratrol from 16 weeks of age until to the
      end of their lives. The mean and maximum life spans of the fish treated with
      resveratrol were extended by 17.34% and 17.66%, respectively, compared to the
      fish in control group. The markers of oxidative stress, such as the levels of
      reactive oxygen species (ROS), the activities of anti-oxidant enzymes, and the
      degree of oxidative damage, were detected at 6, 9, and 12 months, respectively.
      The results showed that levels of ROS and oxidative damage increased and
      activities of anti-oxidant enzymes appeared to decrease with age. Resveratrol
      treatment significantly attenuated the increase of ROS and oxidative damage and
      up-regulated the decrease of anti-oxidant enzyme activities induced by aging. Our
      results demonstrated that resveratrol decreased oxidative stress and extended
      life span in this short-lived fish.

PMID- 25569125
TI  - Validity of screening methods for periodontitis using salivary hemoglobin level
      and self-report questionnaires in people with disabilities.
AB  - BACKGROUND: The aim of this study is to evaluate the validity of screening
      methods in predicting periodontitis in people with disabilities using the
      objective salivary hemoglobin level, a subjective self-report questionnaire, and
      a combined model of the two methods with demographic characteristics. METHODS:
      The participants were 195 patients with disabilities aged >18 years who were
      examined using the community periodontal index (CPI), salivary hemoglobin level,
      and answers to 10 self-report questions (n = 192). Multivariable logistic
      regression and receiver operating characteristic (ROC) curve analysis were
      performed to evaluate the validity of the methods and the combined model in
      predicting the prevalence of >=CPI 3 (probing depth [PD] >=4 mm) or CPI 4 (PD >=6
      mm). RESULTS: Overall, 75.9% of the study group (148 of 195) were diagnosed with
      >=CPI 3, and 38.5% of the study group (75 of 195) were diagnosed with CPI 4. The
      areas under the ROC curve (AUCs) of the salivary hemoglobin level were 0.578
      (sensitivity of 41% and specificity of 77%) and 0.662 (sensitivity of 53% and
      specificity of 75%) for predicting the prevalence of >=CPI 3 and CPI 4,
      respectively. Multivariable modeling incorporating four different questions for
      predicting >=CPI 3 or CPI 4 indicated higher AUCs of 0.710 and 0.732,
      respectively, yielding higher sensitivity (55% for >=CPI 3 and 69% for CPI 4)
      than that of salivary hemoglobin level. The most useful prediction models for
      >=CPI 3 or CPI 4 were combined models, which yielded AUCs of 0.773 and 0.807,
      respectively, with sensitivity values of 70% and specificity values >75%.
      CONCLUSION: The salivary hemoglobin level, self-report questionnaire, and the
      combined method demonstrated screening potential that could predict the
      population prevalence of >=CPI 3 or CPI 4.

PMID- 25569127
TI  - Computational methodology study of the optical and thermochemical properties of a
      molecular photoswitch.
AB  - We assess how the utilization of different DFT functionals for obtaining the
      equilibrium geometries and vibrational frequencies affect the description of the
      thermochemistry and subsequent calculation of the optical properties of a
      dihydroazulene-vinylheptafulvene photoswitch. The assessment covers nine popular
      DFT functionals (BLYP, B3LYP, CAM-B3LYP, M06-L, M06, M06-2X, PBE, PBE0, and
      omegaB97X-D) in conjugation with five different Pople style basis sets (6
      31+G(d), 6-31++G(d,p), 6-311+G(d), 6-311++G(d,p), and 6-311++G(3df,3pd)). It is
      identified that only CAM-B3LYP, M06-2X, and PBE0 are able to quantitatively
      describe the correct trends in the thermochemical properties. The subsequent
      calculation of the optical properties using the CAM-B3LYP functional shows that
      there is little difference in whether the CAM-B3LYP, M06-2X, or PBE0 functionals
      have been used to calculate the equilibrium geometries. Utilizing the identified
      functionals, we investigate how the number of electron withdrawing cyano
      substituents influence the thermochemistry and optical properties of the
      molecular photoswitch. 

PMID- 25569129
TI  - Investigation on deterrence effect of legal punishment measures on driving after
      drinking in Chongqing, China.
AB  - OBJECTIVE: Driving after drinking is one of the main causes associated with road
      accidents in China. China has been concerned about this serious problem and
      updated the regulations of road traffic safety law about driving after drinking 3
      times in the last 10 years to deter this offense. The deterrence effect of the
      current punishment measures implemented since January 2013 was studied in this
      article. METHODS: Data applied in the study were collected by questionnaire
      surveys carried out in Chongqing, a city in southwest China. A total of 329
      drivers participated in 3 rounds of the survey and a 5-point scale rating was
      applied in the investigation. RESULTS: There was a slight difference between
      drivers' familiarity of the law regarding driving after drinking in April 2013
      and April 2014. The perceived certainty of being caught for driving after
      drinking was higher in April 2013 than in April 2014 and it had a time-dependent
      decreasing tendency. Our investigations also show that license suspension is the
      most practical and effective measure and penalty points system ranks second. A
      monetary fine appears to be inefficient to achieve the desired effects.
      CONCLUSIONS: The fourth edition of the Road Traffic Safety Law of the People's
      Republic of China, which took effect in January 2013 coinciding with the
      application of random breath testing and intensification of enforcement activity,
      is effective in deterring driving after drinking according to our investigation.
      More measures should be implemented to change the decreasing tendency of
      perceived certainty of being caught for driving after drinking. An increase in
      the monetary fine is suggested.

PMID- 25569130
TI  - Glycosylation of quinone-fused polythiophene for reagentless and label-free
      detection of E. coli.
AB  - In this report, a new polythiophene interface is fabricated containing fused
      quinone moieties which are then glycosylated to form a carbohydrate platform for
      bacterial detection. Very importantly, this interface can be used for label-free
      and reagentless detection, both by electrochemical and Quartz Crystal
      Microbalance (QCM) transducers and by using the direct pili-mannose binding as
      well as Concanavalin A (Con A) mediated lipopolysaccharides (LPS)-mannose
      binding. The conductive polymer's unique collective properties are very sensitive
      to very minor perturbations, which result in significant changes of electrical
      conductivity and providing amplified sensitivity and improved limits of detection
      (i.e., 25 cell/mL for electrochemical sensor and 50 cells/mL for QCM sensor), a
      widened logarithmic range of detection (i.e., 3-7 for pili-mannose binding and 2
      8 for Con A mediated binding), high specificity and selectivity, and an
      extraordinary reliability by a mechanism of internal validation. With these
      analytical performances, the described biosensor is envisaged for being capable
      of differentiating Gram-negative bacterial strain and species, for many important
      applications. 

PMID- 25569128
TI  - Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase
      II randomised clinical trial.
AB  - OBJECTIVE: To determine if it is possible to stabilise the cerebral oxygenation
      of extremely preterm infants monitored by cerebral near infrared spectroscopy
      (NIRS) oximetry. DESIGN: Phase II randomised, single blinded, parallel clinical
      trial. SETTING: Eight tertiary neonatal intensive care units in eight European
      countries. PARTICIPANTS: 166 extremely preterm infants born before 28 weeks of
      gestation: 86 were randomised to cerebral NIRS monitoring and 80 to blinded NIRS
      monitoring. The only exclusion criterion was a decision not to provide life
      support. INTERVENTIONS: Monitoring of cerebral oxygenation using NIRS in
      combination with a dedicated treatment guideline during the first 72 hours of
      life (experimental) compared with blinded NIRS oxygenation monitoring with
      standard care (control). MAIN OUTCOME MEASURES: The primary outcome measure was
      the time spent outside the target range of 55-85% for cerebral oxygenation
      multiplied by the mean absolute deviation, expressed in %hours (burden of hypoxia
      and hyperoxia). One hour with an oxygenation of 50% gives 5%hours of hypoxia.
      Secondary outcomes were all cause mortality at term equivalent age and a brain
      injury score assessed by cerebral ultrasonography. RANDOMISATION: Allocation
      sequence 1:1 with block sizes 4 and 6 in random order concealed for the
      investigators. The allocation was stratified for gestational age (<26 weeks or >=
      26 weeks). BLINDING: Cerebral oxygenation measurements were blinded in the
      control group. All outcome assessors were blinded to group allocation. RESULTS:
      The 86 infants randomised to the NIRS group had a median burden of hypoxia and
      hyperoxia of 36.1%hours (interquartile range 9.2-79.5%hours) compared with 81.3
      (38.5-181.3) %hours in the control group, a reduction of 58% (95% confidence
      interval 35% to 73%, P<0.001). In the experimental group the median burden of
      hypoxia was 16.6 (interquartile range 5.4-68.1) %hours, compared with 53.6 (17.4
      171.3) %hours in the control group (P=0.0012). The median burden of hyperoxia was
      similar between the groups: 1.2 (interquartile range 0.3-9.6) %hours in the
      experimental group compared with 1.1 (0.1-23.4) %hours in the control group
      (P=0.98). We found no statistically significant differences between the two
      groups at term corrected age. No severe adverse reactions were associated with
      the device. CONCLUSIONS: Cerebral oxygenation was stabilised in extremely preterm
      infants using a dedicated treatment guideline in combination with cerebral NIRS
      monitoring.Trial registration ClinicalTrial.gov NCT01590316.

PMID- 25569131
TI  - Effect-based detection of synthetic glucocorticoids in bovine urine.
AB  - Challenges to testing for the illicit use of anabolic substances in meat
      producing animals stem from the production of new synthetic compounds and the
      administration of low-dose cocktails to circumvent detection by the surveillance
      schemes of European Union member states. This work evaluated for the first time
      GR-CALUX, a highly sensitive reporter gene assay, as a screening tool for the
      detection of synthetic glucocorticoids in bovine urine. In order to verify the
      effect of natural corticosteroids on the method, the bioassay was tested first
      using blank urine samples collected at the farm and the slaughterhouse. Next, the
      dose-response curves were measured for the most commonly used synthetic
      glucocorticoids. The bioassay's ability to detect them in spiked and incurred
      samples of bovine urine was then evaluated. Finally, its performance was compared
      against a commercially available ELISA kit ordinarily used in screening
      activities. GR-CALUX performance did not appear to be influenced by physiological
      levels of endogenous corticosteroids in the farm samples, whereas an increase in
      these hormones might invalidate the analysis in samples obtained at the
      slaughterhouse. Using pure compounds, GR-CALUX showed a high sensitivity toward
      the synthetic glucocorticosteroids tested in order of relative potencies:
      flumethasone ? dexamethasone > betamethasone > methylprednisolone > prednisolone.
      As expected, the bioassay failed to detect the prohormone prednisone. The results
      obtained from analysis of the spiked and incurred specimens reproduced those of
      the blank samples and the pure compounds. GR-CALUX is a promising screening tool
      for the detection of illicit treatments in meat-producing bovines. Its ability to
      detect the most commonly used synthetic glucocorticoids was comparable with the
      ELISA test. Importantly, it appeared to be less susceptible to matrix effects
      than ELISA.

PMID- 25569132
TI  - Nur1 dephosphorylation confers positive feedback to mitotic exit phosphatase
      activation in budding yeast.
AB  - Substrate dephosphorylation by the cyclin-dependent kinase (Cdk)-opposing
      phosphatase, Cdc14, is vital for many events during budding yeast mitotic exit.
      Cdc14 is sequestered in the nucleolus through inhibitory binding to Net1, from
      which it is released in anaphase following Net1 phosphorylation. Initial Net1
      phosphorylation depends on Cdk itself, in conjunction with proteins of the Cdc14
      Early Anaphase Release (FEAR) network. Later on, the Mitotic Exit Network (MEN)
      signaling cascade maintains Cdc14 release. An important unresolved question is
      how Cdc14 activity can increase in early anaphase, while Cdk activity, that is
      required for Net1 phosphorylation, decreases and the MEN is not yet active. Here
      we show that the nuclear rim protein Nur1 interacts with Net1 and, in its Cdk
      phosphorylated form, inhibits Cdc14 release. Nur1 is dephosphorylated by Cdc14 in
      early anaphase, relieving the inhibition and promoting further Cdc14 release.
      Nur1 dephosphorylation thus describes a positive feedback loop in Cdc14
      phosphatase activation during mitotic exit, required for faithful chromosome
      segregation and completion of the cell division cycle. 

PMID- 25569135
TI  - Systematic review of sub-microscopic P. vivax infections: prevalence and
      determining factors.
AB  - BACKGROUND: Sub-microscopic (SM) Plasmodium infections represent transmission
      reservoirs that could jeopardise malaria elimination goals. A better
      understanding of the epidemiology of these infections and factors contributing to
      their occurrence will inform effective elimination strategies. While the
      epidemiology of SM P. falciparum infections has been documented, that of SM P.
      vivax infections has not been summarised. The objective of this study is to
      address this deficiency. METHODOLOGY/PRINCIPAL FINDINGS: A systematic search of
      PubMed was conducted, and results of both light microscopy (LM) and polymerase
      chain reaction (PCR)-based diagnostic tests for P. vivax from 44 cross-sectional
      surveys or screening studies of clinical malaria suspects were analysed. Analysis
      revealed that SM P. vivax is prevalent across different geographic areas with
      varying transmission intensities. On average, the prevalence of SM P. vivax in
      cross-sectional surveys was 10.9%, constituting 67.0% of all P. vivax infections
      detected by PCR. The relative proportion of SM P. vivax is significantly higher
      than that of the sympatric P. falciparum in these settings. A positive
      relationship exists between PCR and LM P. vivax prevalence, while there is a
      negative relationship between the proportion of SM P. vivax and the LM prevalence
      for P. vivax. Amongst clinical malaria suspects, however, SM P. vivax was not
      identified. CONCLUSIONS/SIGNIFICANCE: SM P. vivax is prevalent across different
      geographic areas, particularly areas with relatively low transmission intensity.
      Diagnostic tools with sensitivity greater than that of LM are required for
      detecting these infection reservoirs. In contrast, SM P. vivax is not prevalent
      in clinical malaria suspects, supporting the recommended use of quality LM and
      rapid diagnostic tests in clinical case management. These findings enable malaria
      control and elimination programs to estimate the prevalence and proportion of SM
      P. vivax infections in their settings, and develop appropriate elimination
      strategies to tackle SM P. vivax to interrupt transmission.

PMID- 25569137
TI  - Control of five contiguous stereogenic centers in an organocatalytic kinetic
      resolution via Michael/acetalization sequence: synthesis of fully substituted
      tetrahydropyranols.
AB  - An organocatalytic kinetic resolution of racemic secondary nitroallylic alcohols
      via Michael/acetalization sequence to give fully substituted tetrahydropyranols
      is described. The process affords the products with high to excellent
      stereoselectivities (up to 19.9:1.5:1 dr and 98% ee). The highly enantioenriched,
      less reactive (S)-nitroallylic alcohols 3 were isolated with good to high
      chemical yields (30-44%). The synthetic application of the resolved substrate is
      shown toward the synthesis of enantioenriched (+)-(2S,3R)-3-amino-2-hydroxy-4
      phenylbutyric acid. 

PMID- 25569136
TI  - Intravenous versus intra-arterial thrombolysis in ischemic stroke: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Reperfusion following ischemic stroke can be attained by either
      intravenous thrombolysis (IVT) or intra-arterial thrombolysis (IAT). Only a
      limited number of randomized prospective studies have compared the efficacy and
      safety of IVT and IAT. This meta-analysis investigated possible clinical benefits
      of IAT relative to IVT in patients with acute ischemic stroke. METHODS: We
      searched the PubMed, Cochrane, and Google Scholar databases through October 2013
      for manuscripts that describe the findings of randomized controlled or
      prospective studies that evaluated the outcomes of patients with ischemic stroke
      who were treated with IVT or IAT. The clinical outcome measures were score on the
      modified Rankin scale (mRS) and mortality at 90 days. A favorable outcome was
      defined as an mRS score of 0 to 2. RESULTS: For the mRS, the combined odds ratio
      (OR) of 3.28 (95% confidence interval (CI), 1.91 to 5.65, P < 0.001) indicated
      that patients who received IAT had a significantly higher chance for a favorable
      outcome than did those who received IVT. For mortality, the OR indicated that IAT
      therapy significantly reduced the proportion of patients who died within 90 days
      of the procedure (combined OR, 0.40; 95%CI, 0.17 to 0.92; P = 0.032). CONCLUSION:
      This meta-analysis determined that IAT conferred a significantly greater
      probability of achieving a favorable outcome compared with IVT. There was also a
      significant difference in mortality rates between IAT and IVT. The studies
      included in this analysis were small and heterogeneous; therefore, larger
      randomized prospective clinical studies are necessary to further investigate this
      issue.

PMID- 25569139
TI  - Interpreting atomic force microscopy nanoindentation of hierarchical biological
      materials using multi-regime analysis.
AB  - We present a novel Multi-Regime Analysis (MRA) routine for interpreting force
      indentation measurements of soft materials using atomic force microscopy. The MRA
      approach combines both well established and semi-empirical theories of contact
      mechanics within a single framework to deconvolute highly complex and non-linear
      force-indentation curves. The fundamental assumption in the present form of the
      model is that each structural contribution to the mechanical response acts in
      series with other 'mechanical resistors'. This simplification enables
      interpretation of the micromechanical properties of materials with hierarchical
      structures and it allows automated processing of large data sets, which is
      particularly indispensable for biological systems. We validate the algorithm by
      demonstrating for the first time that the elastic modulus of polydimethylsiloxane
      (PDMS) films is accurately predicted from both approach and retraction branches
      of force-indentation curves. For biological systems with complex hierarchical
      structures, we show the unique capability of MRA to map the micromechanics of
      live plant cells, revealing an intricate sequence of mechanical deformations
      resolved with precision that is unattainable using conventional methods of
      analysis. We recommend the routine use of MRA to interpret AFM force-indentation
      measurements for other complex soft materials including mammalian cells, bacteria
      and nanomaterials. 

PMID- 25569138
TI  - Differential reliance on autophagy for protection from HSV encephalitis between
      newborns and adults.
AB  - Newborns are more susceptible to severe disease from infection than adults, with
      maturation of immune responses implicated as a major factor. The type I
      interferon response delays mortality and limits viral replication in adult mice
      in a model of herpes simplex virus (HSV) encephalitis. We found that intact type
      I interferon signaling did not control HSV disease in the neonatal brain.
      However, the multifunctional HSV protein gamma34.5 involved in countering type I
      interferon responses was important for virulence in the brain in both age groups.
      To investigate this observation further, we studied a specific function of
      gamma34.5 which contributes to HSV pathogenesis in the adult brain, inhibition of
      the cellular process of autophagy. Surprisingly, we found that the beclin binding
      domain of gamma34.5 responsible for inhibiting autophagy was dispensable for HSV
      disease in the neonatal brain, as infection of newborns with the deletion mutant
      decreased time to mortality compared to the rescue virus. Additionally, a
      functional beclin binding domain in HSV gamma34.5 did not effectively inhibit
      autophagy in the neonate, unlike in the adult. Type I IFN responses promote
      autophagy in adult, a finding we confirmed in the adult brain after HSV
      infection; however, in the newborn brain we observed that autophagy was activated
      through a type I IFN-independent mechanism. Furthermore, autophagy in the wild
      type neonatal mouse was associated with increased apoptosis in infected regions
      of the brain. Observations in the mouse model were consistent with those in a
      human case of neonatal HSV encephalitis. Our findings reveal age-dependent
      differences in autophagy for protection from HSV encephalitis, indicating
      developmental differences in induction and regulation of this innate defense
      mechanism after HSV infection in the neonatal brain. 

PMID- 25569141
TI  - Pd(II)-catalyzed enantioselective synthesis of P-stereogenic phosphinamides via
      desymmetric C-H arylation.
AB  - We present the enantioselective synthesis of P-stereogenic phosphinamides through
      Pd-catalyzed desymmetric ortho C-H arylation of diarylphosphinamides with boronic
      esters. The method represents the first example of the synthesis of P-stereogenic
      phosphorus compounds via the desymmetric C-H functionalization strategy. The
      reaction proceeded efficiently with a wide array of reaction partners to afford
      the P-stereogenic phosphinamides in up to 74% yield and 98% ee. The efficiency
      was further demonstrated by gram scale syntheses. Moreover, the flexible
      conversion of the P-stereogenic phosphinamides into various types of P
      stereogenic phosphorus derivatives was also elaborated. Thus, the protocol
      provides a novel tool for the efficient and versatile synthesis of P-stereogenic
      compounds. 

PMID- 25569140
TI  - Malassezia infections in humans and animals: pathophysiology, detection, and
      treatment.

PMID- 25569143
TI  - Scalable, chromatography-free synthesis of alkyl-tethered pyrene-based materials.
      Application to first-generation "archipelago model" asphaltene compounds.
AB  - In this paper, we report a highly efficient, scalable approach to the total
      synthesis of conformationally unrestricted, electronically isolated arrays of
      alkyl-tethered polycyclic aromatic chromophores. This new class of modular
      molecules consists of polycyclic aromatic "islands" comprising significant
      structural fragments present in unrefined heavy petroleum, tethered together by
      short saturated alkyl chains, as represented in the "archipelago model" of
      asphaltene structure. The most highly branched archipelago compounds reported
      here share an architecture with first-generation dendrimeric constructs, making
      the convergent, chromatography-free synthesis described herein particularly
      attractive for further extensions in scope and applications to materials
      chemistry. The syntheses are efficient, selective, and readily adaptable to a
      multigram scale, requiring only inexpensive, "earth-abundant" transition-metal
      catalysts for cross-coupling reactions and extraction and fractional
      crystallization for purification. This approach avoids typical limitations in
      cost, scale, and operational practicality. All of the archipelago compounds and
      synthetic intermediates have been fully characterized spectroscopically and
      analytically. The solid-state structure of one archipelago model compound has
      been determined by X-ray crystallography. 

PMID- 25569142
TI  - Modification of graphene/SiO2 interface by UV-irradiation: effect on electrical
      characteristics.
AB  - Graphene is a promising material for next-generation electronic devices. The
      effect of UV-irradiation on the graphene devices, however, has not been fully
      explored yet. Here we investigate the UV-induced change of the field effect
      transistor (FET) characteristics of graphene/SiO2. UV-irradiation in a vacuum
      gives rise to the decrease in carrier mobility and a hysteresis in the transfer
      characteristics. Annealing at 160  degrees C in a vacuum eliminates the
      hysteresis, recovers the mobility partially, and moves the charge neutrality
      point to the negative direction. Corresponding Raman spectra indicated that UV
      irradiation induced D band relating with defects and the annealing at 160 
      degrees C in a vacuum removed the D band. We propose a phenomenological model for
      the UV-irradiated graphene, in which photochemical reaction produces dangling
      bonds and the weak sp(3)-like bonds at the graphene/SiO2 interface, and the
      annealing restores the intrinsic graphene/SiO2 interface by removal of such
      bonds. Our results shed light to the nature of defect formation by UV-light,
      which is important for the practical performance of graphene based electronics. 

PMID- 25569144
TI  - A five-year-old child with a subcutaneous forehead nodule.
AB  - We describe a case of a 5-year-old girl with onchocerciasis. The patient was
      recently adopted from Ethiopia and presented with a firm, raised nodule on the
      midportion of the forehead. Initially, Langerhans cell histiocytosis with bone
      involvement was suspected; however, histopathologic analysis of the excised
      nodule revealed the presence of a young-adult, female Onchocerca volvulus worm.
      This case exemplifies the importance of recognizing the key morphologic
      characteristics of adult O. volvulus worms isolated from pediatric patients in
      nonendemic areas to ensure adroit clinical management. 

PMID- 25569145
TI  - Distinct photoproducts of hydroxylated polybromodiphenyl ethers from different
      photodegradation pathways: a case study of 2'-HO-BDE-68.
AB  - Hydroxylated polyhalodiphenyl ethers (HO-PXDEs) are emerging aquatic pollutants.
      Previous studies have shown that HO-PXDEs can photogenerate dioxins and phenolic
      compounds. However, it is unclear which photochemical pathways are responsible
      for the various photoproducts. This study investigates the direct photolysis and
      photooxidation initiated by (1)O2 and OH that can be formed by
      photosensitization, taking 2'-HO-2,3',4,5'-tetrabromodiphenyl ether (2'-HO-BDE
      68) as a case study. The results show that 1,3,8-tribromodibenzo-p-dioxin can
      only be produced during direct photolysis. By mass spectrum analysis, four
      dihydroxylated polybromodiphenyl ethers, generated from both direct and indirect
      photodegradation were confirmed. Among them, di-HO-tribromodiphenyl ether (di-HO
      TBDE) was the main product generated from direct photohydrolysis. Most probably,
      the di-HO-TBDE is 2',5'-HO-2,3',4-tribromodiphenyl ether, as was suggested by
      density functional theory calculations. Ether bond cleavage is a dominant pathway
      for the direct photolysis and photooxidation reactions leading to 2,4
      dibromophenol as the dominant product. The yields of the products, which are
      irrespective of reaction time and can be employed to compare the ability of
      different HO-PXDEs to photogenerate a given product, were reported. This study
      indicates that for accurate ecological risk assessment of HO-PXDEs, their
      different photodegradation pathways that may lead to different photoproducts
      should be considered. 

PMID- 25569147
TI  - The impact of nocturnal hypertension and nondipping status on left ventricular
      mass: a cohort study.
AB  - OBJECTIVE: Ambulatory blood pressure monitoring provides a unique tool in the
      evaluation of night-time blood pressure (BP), having a critical role in the
      detection of a blunted nocturnal fall and of elevated night-time BP. Both
      nondipping status and nocturnal hypertension are associated with increased
      cardiovascular risk and target organ damage. The aim of our study was to
      investigate the impact of both nondipping status and nocturnal hypertension on
      left ventricular mass (LVM), assessed by means of echocardiography in a
      consecutive cohort of untreated participants. METHODS: A total of 937 individuals
      were assessed by means of ambulatory blood pressure monitoring and
      echocardiography. Participants were divided into dippers and nondippers with or
      without systolic nocturnal hypertension (SNH). SNH was defined as night-time
      systolic blood pressure of 120 mmHg or more, and nondipping status was defined as
      an average reduction in systolic blood pressure at night less than 10% compared
      with the daytime BP. RESULTS: Dippers and nondippers with SNH presented
      significantly higher values of left ventricular mass index compared with dippers
      and nondippers without SNH, respectively. Multiple regression analysis revealed
      that age (beta=0.182, P<0.001), male gender (beta=0.168, P<0.001), body mass
      index (beta=0.080, P=0.011), and nocturnal SBP (beta=0.174, P=0.037) were
      significant and independent determinants of LVM. Nondipping status was not found
      as an independent factor associated with LVM (P=0.136). CONCLUSION: Nocturnal
      hypertension rather than nondipping status seems to be an independent factor
      associated with left ventricular mass index. The concomitant presence of both
      nondipping status and nocturnal hypertension is associated with higher LVM,
      indicating an enhanced cardiovascular risk.

PMID- 25569148
TI  - Identification of constrained cancer driver genes based on mutation timing.
AB  - Cancer drivers are genomic alterations that provide cells containing them with a
      selective advantage over their local competitors, whereas neutral passengers do
      not change the somatic fitness of cells. Cancer-driving mutations are usually
      discriminated from passenger mutations by their higher degree of recurrence in
      tumor samples. However, there is increasing evidence that many additional driver
      mutations may exist that occur at very low frequencies among tumors. This
      observation has prompted alternative methods for driver detection, including
      finding groups of mutually exclusive mutations and incorporating prior biological
      knowledge about gene function or network structure. Dependencies among drivers
      due to epistatic interactions can also result in low mutation frequencies, but
      this effect has been ignored in driver detection so far. Here, we present a new
      computational approach for identifying genomic alterations that occur at low
      frequencies because they depend on other events. Unlike passengers, these
      constrained mutations display punctuated patterns of occurrence in time. We test
      this driver-passenger discrimination approach based on mutation timing in
      extensive simulation studies, and we apply it to cross-sectional copy number
      alteration (CNA) data from ovarian cancer, CNA and single-nucleotide variant
      (SNV) data from breast tumors and SNV data from colorectal cancer. Among the top
      ranked predicted drivers, we find low-frequency genes that have already been
      shown to be involved in carcinogenesis, as well as many new candidate drivers.
      The mutation timing approach is orthogonal and complementary to existing driver
      prediction methods. It will help identifying from cancer genome data the
      alterations that drive tumor progression. 

PMID- 25569146
TI  - Systems level analysis of systemic sclerosis shows a network of immune and
      profibrotic pathways connected with genetic polymorphisms.
AB  - Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by
      skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly
      understood. The SSc intrinsic gene expression subsets (inflammatory,
      fibroproliferative, normal-like, and limited) are observed in multiple clinical
      cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests
      that a patient's subset assignment is stable over 6-12 months. Genetically, SSc
      is multi-factorial with many genetic risk loci for SSc generally and for specific
      clinical manifestations. Here we identify the genes consistently associated with
      the intrinsic subsets across three independent cohorts, show the relationship
      between these genes using a gene-gene interaction network, and place the genetic
      risk loci in the context of the intrinsic subsets. To identify gene expression
      modules common to three independent datasets from three different clinical
      centers, we developed a consensus clustering procedure based on mutual
      information of partitions, an information theory concept, and performed a meta
      analysis of these genome-wide gene expression datasets. We created a gene-gene
      interaction network of the conserved molecular features across the intrinsic
      subsets and analyzed their connections with SSc-associated genetic polymorphisms.
      The network is composed of distinct, but interconnected, components related to
      interferon activation, M2 macrophages, adaptive immunity, extracellular matrix
      remodeling, and cell proliferation. The network shows extensive connections
      between the inflammatory- and fibroproliferative-specific genes. The network also
      shows connections between these subset-specific genes and 30 SSc-associated
      polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and
      several human leukocyte antigen (HLA) genes. Our analyses suggest that the gene
      expression changes underlying the SSc subsets may be long-lived, but
      mechanistically interconnected and related to a patients underlying genetic risk.

PMID- 25569149
TI  - Low frequency of circulating CD8+ T stem cell memory cells in chronic chagasic
      patients with severe forms of the disease.
AB  - BACKGROUND: CD8+ T cells have been shown to play a crucial role in Trypanosoma
      cruzi infection. Memory CD8+ T cells can be categorised based on their distinct
      differentiation stages and functional activities as follows: stem cell memory
      (TSCM), central memory (TCM), transitional memory (TTM), effector memory (TEM)
      and terminal effector (TTE) cells. Currently, the immune mechanisms that control
      T. cruzi in the chronic phase of the infection are unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: To characterise the CD8+ T cell subsets that could be participating in
      the control of T. cruzi infection, in this study, we compared total and T. cruzi
      specific circulating CD8+ T cells with distinctive phenotypic and functional
      features in chronic chagasic patients (CCPs) with different degrees of cardiac
      dysfunction. We observed a decreased frequency of total TSCM along with an
      increased frequency of TTE in CCPs with severe disease. Antigen-specific TSCM
      cells were not detectable in CCPs with severe forms of the disease. A functional
      profile of CD8+ T cell subsets among CCPs revealed a high frequency of
      monofunctional CD8+ T cells in the most severe patients with IFN-gamma+- or TNF
      alpha+-producing cells. CONCLUSIONS/SIGNIFICANCE: These findings suggest that
      CD8+ TSCM cells may be associated with the immune response to T. cruzi and
      outcome of Chagas disease, given that these cells may be involved in repopulating
      the T cell pool that controls infection.

PMID- 25569150
TI  - Health Literacy and Heart Failure: A Systematic Review.
AB  - BACKGROUND: Low health literacy affects millions of Americans, putting those who
      are affected at a disadvantage and at risk for poorer health outcomes. Low health
      literacy can act as a barrier to effective disease self-management; this is
      especially true for chronic diseases such as heart failure (HF) that require
      complicated self-care regimens. PURPOSE: This systematic review examined
      quantitative research literature published between 1999 and 2014 to explore the
      role of health literacy among HF patients. The specific aims of the systematic
      review are to (1) describe the prevalence of low health literacy among HF
      patients, (2) explore the predictors of low health literacy among HF patients,
      and (3) discuss the relationship between health literacy and HF self-care and
      common HF outcomes. METHODS: A systematic search of the following databases was
      conducted, PubMed, CINAHL Plus, Embase, PsycINFO, and Scopus, using relevant
      keywords and clear inclusion and exclusion criteria. CONCLUSIONS: An average of
      39% of HF patients have low health literacy. Age, race/ethnicity, years of
      education, and cognitive function are predictors of health literacy. In addition,
      adequate health literacy is consistently correlated with higher HF knowledge and
      higher salt knowledge. CLINICAL IMPLICATIONS: Considering the prevalence of low
      health literacy among in the HF population, nurses and healthcare professionals
      need to recognize the consequences of low health literacy and adopt strategies
      that could minimize its detrimental effect on the patient's health outcomes.

PMID- 25569151
TI  - Kinetic and structural mechanisms of (5'S)-8,5'-cyclo-2'-deoxyguanosine-induced
      dna replication stalling.
AB  - The (5'S)-8,5'-cyclo-2'-deoxyguanosine (S-cdG) lesion is produced from reactions
      of DNA with hydroxyl radicals generated from ionizing radiation or endogenous
      oxidative metabolisms. An elevated level of S-cdG has been detected in Xeroderma
      pigmentosum, Cockayne syndrome, breast cancer patients, and aged mice. S-dG
      blocks DNA replication and transcription in vitro and in human cells and produces
      mutant replication and transcription products in vitro and in vivo. Major
      cellular protection against S-dG includes nucleotide excision repair and
      translesion DNA synthesis. We used kinetic and crystallographic approaches to
      elucidate the molecular mechanisms of S-cdG-induced DNA replication stalling
      using model B-family Sulfolobus solfataricus P2 DNA polymerase B1 (Dpo1) and Y
      family S. solfataricus P2 DNA polymerase IV (Dpo4). Dpo1 and Dpo4 inefficiently
      bypassed S-cdG with dCTP preferably incorporated and dTTP (for Dpo4) or dATP (for
      Dpo1) misincorporated. Pre-steady-state kinetics and crystallographic data
      mechanistically explained the low-efficiency bypass. For Dpo1, S-cdG attenuated
      Kd,dNTP,app and kpol. For Dpo4, the S-cdG-adducted duplex caused a 6-fold
      decrease in Dpo4:DNA binding affinity and significantly reduced the concentration
      of the productive Dpo4:DNA:dCTP complex. Consistent with the inefficient bypass,
      crystal structures of Dpo4:DNA(S-cdG):dCTP (error-free) and Dpo4:DNA(S-cdG):dTTP
      (error-prone) complexes were catalytically incompetent. In the Dpo4:DNA(S
      cdG):dTTP structure, S-cdG induced a loop structure and caused an unusual 5'
      template base clustering at the active site, providing the first structural
      evidence of the previously suggested template loop structure that can be induced
      by a cyclopurine lesion. Together, our results provided mechanistic insights into
      S-cdG-induced DNA replication stalling. 

PMID- 25569152
TI  - Programmed chemo-enzymatic synthesis of the oligosaccharide component of a
      carbohydrate-based antibacterial vaccine candidate.
AB  - The powerful chemo-enzymatic synthesis of the pentadecasaccharide hapten involved
      in the first synthetic carbohydrate-based vaccine candidate against endemic
      shigellosis is reported. The high yielding site-selective alpha-D-glucosylation
      of a lightly protected disaccharide by an engineered transglucosylase-sucrose
      system gave a trisaccharide, which was chemically elongated by an efficient [5+5]
      process.

PMID- 25569153
TI  - The molecular basis for control of ETEC enterotoxin expression in response to
      environment and host.
AB  - Enterotoxigenic Escherichia coli (ETEC) cause severe diarrhoea in humans and
      neonatal farm animals. Annually, 380,000 human deaths, and multi-million dollar
      losses in the farming industry, can be attributed to ETEC infections. Illness
      results from the action of enterotoxins, which disrupt signalling pathways that
      manage water and electrolyte homeostasis in the mammalian gut. The resulting
      fluid loss is treated by oral rehydration. Hence, aqueous solutions of glucose
      and salt are ingested by the patient. Given the central role of enterotoxins in
      disease, we have characterised the regulatory trigger that controls toxin
      production. We show that, at the molecular level, the trigger is comprised of two
      gene regulatory proteins, CRP and H-NS. Strikingly, this renders toxin expression
      sensitive to both conditions encountered on host cell attachment and the
      components of oral rehydration therapy. For example, enterotoxin expression is
      induced by salt in an H-NS dependent manner. Furthermore, depending on the toxin
      gene, expression is activated or repressed by glucose. The precise sensitivity of
      the regulatory trigger to glucose differs because of variations in the regulatory
      setup for each toxin encoding gene. 

PMID- 25569154
TI  - The transforming growth factor beta signaling pathway is critical for the
      formation of CD4 T follicular helper cells and isotype-switched antibody
      responses in the lung mucosa.
AB  - T follicular helper cells (Tfh) are crucial for the initiation and maintenance of
      germinal center (GC) reactions and high affinity, isotype-switched antibody
      responses. In this study, we demonstrate that direct TGF-beta signaling to CD4 T
      cells is important for the formation of influenza-specific Tfh cells, GC
      reactions, and development of isotype-switched, flu-specific antibody responses.
      Early during infection, TGF-beta signaling suppressed the expression of the high
      affinity IL-2 receptor alpha chain (CD25) on virus-specific CD4 T cells, which
      tempered IL-2 signaling and STAT5 and mammalian target of rapamycin (mTOR)
      activation in Tfh precursor CD4 T cells. Inhibition of mTOR allowed for the
      differentiation of Tfh cells in the absence of TGF-betaR signaling, suggesting
      that TGF-beta insulates Tfh progenitor cells from IL-2-delivered mTOR signals,
      thereby promoting Tfh differentiation during acute viral infection. These
      findings identify a new pathway critical for the generation of Tfh cells and
      humoral responses during respiratory viral infections. 

PMID- 25569155
TI  - Activity and Ca2+ regulate the mobility of TRPV1 channels in the plasma membrane
      of sensory neurons.
AB  - TRPV1 channels are gated by a variety of thermal, chemical, and mechanical
      stimuli. We used optical recording of Ca(2+) influx through TRPV1 to measure
      activity and mobility of single TRPV1 molecules in isolated dorsal root ganglion
      neurons and cell lines. The opening of single TRPV1 channels produced sparklets,
      representing localized regions of elevated Ca(2+). Unlike sparklets reported for
      L-type Ca(2+) channels, TRPV4 channels, and AchR channels, TRPV1 channels
      diffused laterally in the plasma membrane as they gated. Mobility was highly
      variable from channel-to-channel and, to a smaller extent, from cell to cell.
      Most surprisingly, we found that mobility decreased upon channel activation by
      capsaicin, but only in the presence of extracellular Ca(2+). We propose that
      decreased mobility of open TRPV1 could act as a diffusion trap to concentrate
      channels in cell regions with high activity. 

PMID- 25569156
TI  - The majority of transcripts in the squid nervous system are extensively recoded
      by A-to-I RNA editing.
AB  - RNA editing by adenosine deamination alters genetic information from the genomic
      blueprint. When it recodes mRNAs, it gives organisms the option to express
      diverse, functionally distinct, protein isoforms. All eumetazoans, from
      cnidarians to humans, express RNA editing enzymes. However, transcriptome-wide
      screens have only uncovered about 25 transcripts harboring conserved recoding RNA
      editing sites in mammals and several hundred recoding sites in Drosophila. These
      studies on few established models have led to the general assumption that
      recoding by RNA editing is extremely rare. Here we employ a novel bioinformatic
      approach with extensive validation to show that the squid Doryteuthis pealeii
      recodes proteins by RNA editing to an unprecedented extent. We identify 57,108
      recoding sites in the nervous system, affecting the majority of the proteins
      studied. Recoding is tissue-dependent, and enriched in genes with neuronal and
      cytoskeletal functions, suggesting it plays an important role in brain
      physiology. 

PMID- 25569157
TI  - Neuron-wide RNA transport combines with netrin-mediated local translation to
      spatially regulate the synaptic proteome.
AB  - The persistence of experience-dependent changes in brain connectivity requires
      RNA localization and protein synthesis. Previous studies have demonstrated a role
      for local translation in altering the structure and function of synapses during
      synapse formation and experience-dependent synaptic plasticity. In this study, we
      ask whether in addition to promoting local translation, local stimulation also
      triggers directed trafficking of RNAs from nucleus to stimulated synapses.
      Imaging of RNA localization and translation in cultured Aplysia sensory-motor
      neurons revealed that RNAs were delivered throughout the arbor of the sensory
      neuron, but that translation was enriched only at sites of synaptic contact
      and/or synaptic stimulation. Investigation of the mechanisms that trigger local
      translation revealed a role for calcium-dependent retrograde netrin-1/DCC
      receptor signaling. Spatially restricting gene expression by regulating local
      translation rather than by directing the delivery of mRNAs from nucleus to
      stimulated synapses maximizes the readiness of the entire neuronal arbor to
      respond to local cues. 

PMID- 25569159
TI  - Genome-wide identification of CBX2 targets: insights in the human sex development
      network.
AB  - Chromobox homolog 2 (CBX2) is a chromatin modifier that plays an important role
      in sexual development and its disorders (disorders of sex development [DSD]), yet
      the exact rank and function of human CBX2 in this pathway remains unclear. Here,
      we performed large-scale mapping and analysis of in vivo target loci of the
      protein CBX2 in Sertoli-like NT-2D1 cells, using the DNA adenine
      methyltransferase identification technique. We identified close to 1600 direct
      targets for CBX2. Intriguingly, validation of selected candidate genes using qRT
      PCR in cells overexpressing CBX2 or in which CBX2 has been knocked down indicated
      that several CBX2-responsive genes encode proteins that are involved in DSD. We
      further validated these effects on the candidate genes using a mutated CBX2
      causing DSD in human patient. Overall, our findings suggest that CBX2 role in the
      sex development cascade is to stimulate the male pathway and concurrently inhibit
      the female pathway. These data provide fundamental insights into potential
      etiology of DSD. 

PMID- 25569161
TI  - A changing model for developing health products for poverty-related infectious
      diseases.

PMID- 25569160
TI  - Intercellular communication by extracellular vesicles with emphasis on the roles
      of cordocytes in the human brain. An ultrastructural study.
AB  - We describe in this work the presence of extracellular vesicles (EVs) along
      different cell types, especially cordocytes, in various clinical conditions of
      the human brain (atherothrombotic disease, cerebral tumors, hygroma durae matris,
      intracerebral cysts, Moyamoya disease and parenchymatous hematoma) using
      transmission electron microscopy (TEM). EVs, illustrated as exosomes and
      microvesicles, were causally related to cell-to-cell communication, and other
      vital functions of resident cells around the brain parenchyma, either around the
      cortical vessels or into the subarachnoid space and the reticular arachnoid. Our
      direct demonstration by TEM of these information transporters in all locations
      and situations where the cordocytes play coordinating and regulating roles,
      producing and delivering a significant number of EVs to their targets, remains to
      be better documented in future studies. This first study on this topic showed
      clearly that EVs can be important modulators of cell functions with roles in cell
      activation, differentiation, phenotypic change, cancer progression, from
      precursor/stem cells to tumoral phenotypes, because EVs are released en masse
      during key interactions and certain moments. 

PMID- 25569158
TI  - IGSF4 methylation as an independent marker of human papillomavirus-positive
      oropharyngeal squamous cell carcinoma.
AB  - IMPORTANCE: Human papillomavirus (HPV) is a known causative agent for
      oropharyngeal squamous cell carcinoma (OPSCC). Whereas it is becoming more firmly
      established that HPV-positive head and neck squamous cell carcinoma is associated
      with better survival outcomes, believed to be because of better response to
      chemoradiation therapy, the specific mechanisms for these improved survival
      outcomes remain underexplored. OBJECTIVE: To examine the relationship between HPV
      status and promoter methylation in an OPSCC cohort. DESIGN, SETTING, AND
      PARTICIPANTS: Real-time quantitative polymerase chain reaction was used to
      examine oncogenic HPV type 16 in a retrospective cohort of 121 patients with
      primary OPSCC. Aberrant promoter methylation of IGSF4, DAPK1, and ESR1 genes,
      known to be methylated in head and neck squamous cell carcinoma, including OPSCC,
      was examined by means of quantitative methylation-specific polymerase chain
      reaction. INTERVENTIONS: Patients received standard therapy. MAIN OUTCOMES AND
      MEASURES: Univariate associations between HPV and methylation were analyzed using
      Fisher exact tests followed by multivariable logistic regression. Cox
      proportional-hazards regression was used to model the risk of death given age,
      race, sex, HPV status, methylation, stage, smoking, and treatment. RESULTS: In
      univariate logistic regression analyses, HPV-positive status was significantly
      associated with Caucasian race (P = .02), treatment (radiotherapy only, P = .01;
      chemoradiotherapy, P = .007), and IGSF4 methylation (P = .005). The final
      multivariate logistic model, after controlling for patient characteristics (sex,
      age, smoking, race, and treatment) with backward variable selection among genes,
      retained IGSF4 methylation (OR, 4.5 [95% CI, 1.6-12.8]; P = .005), Caucasian race
      (OR, 2.9 [95% CI, 1.0-8.3]; P = .053), treatment (radiotherapy only vs neither:
      OR, 11.62 [95% CI, 2.02-66.82]; P = .02; chemoradiotherapy vs neither: OR, 11.15
      [95% CI, 1.92-64.65]; P = .01), male sex (OR, 4.7 [95% CI, 1.3-17.0]; P = .02),
      and younger age (OR, 0.9 [95% CI, 0.90-1.0]; P = .008) as independent predictors
      of HPV-positive status. Cox regression modeling indicated HPV-negative status,
      age, male sex, smoking, and radiation treatment as independent predictors of
      mortality. CONCLUSIONS AND RELEVANCE: Methylation of IGSF4 is an independent
      predictor of HPV-positive status. DNA methylation in conjunction with HPV
      infection appears to play a role in OPSCC.

PMID- 25569162
TI  - Influence of high-pressure homogenization, ultrasonication, and supercritical
      fluid on free astaxanthin extraction from beta-glucanase-treated Phaffia
      rhodozyma cells.
AB  - In this study astaxanthin production by Phaffia rhodozyma was enhanced by
      chemical mutation using ethyl methane sulfonate. The mutant produces a higher
      amount of astaxanthin than the wild yeast strain. In comparison to supercritical
      fluid technique, high-pressure homogenization is better for extracting
      astaxanthin from yeast cells. Ultrasonication of dimethyl sulfoxide, hexane, and
      acetone-treated cells yielded less astaxanthin than beta-glucanase enzyme-treated
      cells. The combination of ultrasonication with beta-glucanase enzyme is found to
      be the most efficient method of extraction among all the tested physical and
      chemical extraction methods. It gives a maximum yield of 435.71 +/- 6.55 ug free
      astaxanthin per gram of yeast cell mass.

PMID- 25569163
TI  - Caffeic Acid-PLGA Conjugate to Design Protein Drug Delivery Systems Stable to
      Irradiation.
AB  - This work reports the feasibility of caffeic acid grafted PLGA (g-CA-PLGA) to
      design biodegradable sterile microspheres for the delivery of proteins. Ovalbumin
      (OVA) was selected as model compound because of its sensitiveness of gamma
      radiation. The adopted grafting procedure allowed us to obtain a material with
      good free radical scavenging properties, without a significant modification of Mw
      and Tg of the starting PLGA (Mw PLGA = 26.3 +/- 1.3 kDa vs. Mw g-CA-PLGA = 22.8
      +/- 0.7 kDa; Tg PLGA = 47.7 +/- 0.8  degrees C vs. Tg g-CA-PLGA = 47.4 +/- 0.2 
      degrees C). By using a W1/O/W2 technique, g-CA-PLGA improved the encapsulation
      efficiency (EE), suggesting that the presence of caffeic residues improved the
      compatibility between components (EEPLGA = 35.0% +/- 0.7% vs. EEg-CA-PLGA = 95.6%
      +/- 2.7%). Microspheres particle size distribution ranged from 15 to 50 um. The
      zeta-potential values of placebo and loaded microspheres were -25 mV and -15 mV,
      respectively. The irradiation of g-CA-PLGA at the dose of 25 kGy caused a less
      than 1% variation of Mw and the degradation patterns of the non-irradiated and
      irradiated microspheres were superimposable. The OVA content in g-CA-PLGA
      microspheres decreased to a lower extent with respect to PLGA microspheres. These
      results suggest that g-CA-PLGA is a promising biodegradable material to
      microencapsulate biological drugs. 

PMID- 25569165
TI  - New resources for audiologists working with Hispanic patients: Spanish
      translations and cultural training.
AB  - PURPOSE: Hispanics comprise over 16% of the U.S. population (Humes, Jones, &
      Ramirez, 2011). Cultural and language differences may negatively affect services
      audiologists provide to Hispanic patients. The purpose of the current study was
      to assist monolingual English-speaking audiologists working with Spanish-speaking
      Hispanic patients by developing appropriate cultural and language instruction
      materials. METHOD: Test descriptions and instructions for hearing and balance
      tests were developed in English and Spanish. A cultural training module was also
      created. The first draft of these resources was reviewed by nonaudiologists
      (bilingual and Spanish monolingual) and audiologists (bilingual and English
      monolingual). Videos were recorded of the Spanish test instructions read aloud.
      RESULTS: Overall, ratings from audiologists and nonaudiologists indicated the
      translations were easy to understand, and the wording/dialect was appropriate for
      the region. Audiologists generally reported the information was consistent with
      what they use clinically, although variability existed in specific wording used.
      Reviewers rated the cultural training module as easy to understand, relevant to
      Spanish-speaking patients, and relevant to audiologists. The materials were
      revised and edited based on feedback from reviewers. CONCLUSIONS: The current
      study developed materials for monolingual English-speaking audiologists working
      with Spanish-speaking Hispanic patients. The final translations are provided as
      online supplemental materials.

PMID- 25569166
TI  - Epiblepharon-induced head tilt masquerading as torticollis.
AB  - A 10-month-old girl presented for ocular evaluation carrying a provisional
      diagnosis of torticollis. Her family reported that for the past 5 months, she
      consistently tilted her head to the left while twisting her chin toward the right
      shoulder. Her adnexal examination was notable for epiblepharon, with greater
      ciliary-corneal contact in the OS. It was therefore hypothesized that this
      posture was adopted to minimize ocular irritation. Her symptoms resolved
      immediately following a Hotz-Celsus procedure. To the best of the authors'
      knowledge, this is the first report of asymmetric ciliary-corneal contact from
      epiblepharon, resulting in preference for a head position mimicking a
      musculoskeletal abnormality such as torticollis. 

PMID- 25569164
TI  - Pyrethroid-resistance and presence of two knockdown resistance (kdr) mutations,
      F1534C and a novel mutation T1520I, in Indian Aedes aegypti.
AB  - BACKGROUND: Control of Aedes aegypti, the mosquito vector of dengue, chikungunya
      and yellow fever, is a challenging task. Pyrethroid insecticides have emerged as
      a preferred choice for vector control but are threatened by the emergence of
      resistance. The present study reports a focus of pyrethroid resistance and
      presence of two kdr mutations--F1534C and a novel mutation T1520I, in Ae. aegypti
      from Delhi, India. METHODOLOGY/PRINCIPAL FINDINGS: Insecticide susceptibility
      status of adult-female Ae. aegypti against DDT (4%), deltamethrin (0.05%) and
      permethrin (0.75%) was determined using WHO's standard insecticide susceptibility
      kit, which revealed resistance to DDT, deltamethrin and permethrin with corrected
      mortalities of 35%, 72% and 76% respectively. Mosquitoes were screened for the
      presence of kdr mutations including those reported earlier (I1011V/M, V1016G/I,
      F1534C, D1794Y and S989P), which revealed the presence of F1534C and a novel
      mutation T1520I. Highly specific PCR-RFLP assays were developed for genotyping of
      these two mutations. Genotyping using allele specific PCR and new PCR-RFLP assays
      revealed a high frequency of F1534C (0.41-0.79) and low frequency of novel
      mutation T1520I (0.13). The latter was observed to be tightly linked with F1534C
      and possibly serve as a compensatory mutation. A positive association of F1534C
      mutation with DDT and deltamethrin resistance in Ae. aegypti was established.
      However, F1534C-kdr did not show significant protection against permethrin.
      CONCLUSIONS/SIGNIFICANCE: The Aedes aegypti population of Delhi is resistant to
      DDT, deltamethrin and permethrin. Two kdr mutations, F1534C and a novel mutation
      T1520I, were identified in this population. This is the first report of kdr
      mutations being present in the Indian Ae. aegypti population. Highly specific PCR
      RFLP assays were developed for discrimination of alleles at both kdr loci. A
      positive association of F1534C mutation with DDT and deltamethrin resistance was
      confirmed.

PMID- 25569167
TI  - Competing interests in epidemiology.

PMID- 25569169
TI  - Galactose targeted pH-responsive copolymer conjugated with near infrared
      fluorescence probe for imaging of intelligent drug delivery.
AB  - Theranostic polymeric nanomaterials are of special important in cancer treatment.
      Here, novel galactose targeted pH-responsive amphiphilic multiblock copolymer
      conjugated with both drug and near-infrared fluorescence (NIR) probe has been
      designed and prepared by a four-steps process: (1) ring-opening polymerization
      (ROP) of N-carboxy anhydride (NCA) monomers using propargylamine as initiator;
      (2) reversible addition-fragmentation chain transfer (RAFT) polymerization of
      oligo(ethylene glycol) methacrylate (OEGMA) and gal monomer by an azido modified
      RAFT agent; (3) combing the obtained two polymeric segments by click reaction;
      (4) NIR copolymer prodrug was synthesized by chemical linkage of both cyanine dye
      and anticancer drug doxorubicin to the block copolymer via amide bond and
      hydrazone, respectively. The obtained NIRF copolymers were characterized by
      nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), and its
      was measured by means of micelles dynamic light scattering (DLS), field emission
      transmission electron microscopy (FETEM), and UV-vis and fluorescence
      spectrophotometry. The prodrug has strong fluorescence in the near-infrared
      region, and a pH sensitive drug release was confirmed at pH of 5.4 via an in
      vitro drug release experiment. Confocal laser scanning microscopy (CLSM) and flow
      cytometry experiments of the prodrug on both HepG2 and NIH3T3 cells reveal that
      the galactose targeted polymeric prodrug shows a fast and enhanced endocytosis
      due to the specific interaction for HepG2 cells, indicating the as-prepared
      polymer is a candidate for theranosis of liver cancer. 

PMID- 25569171
TI  - Role of noncovalent interactions in vanadium tellurite chain connectivities.
AB  - Structural differences in [V2Te2O10]n(2n-) chain metrics are directly ascribed to
      variations in noncovalent interactions in a series of organically templated
      vanadium tellurites, including [C6H17N3][V2Te2O10].H2O, [C5H16N2][V2Te2O10], and
      [C4H14N2][V2Te2O10]. The noncovalent interaction (NCI) method was used to locate,
      quantify, and visualize intermolecular interactions in [C4H14N2][V2Te2O10] and
      [C5H16N2][V2Te2O10]. Variations in the van der Waals attractions between [1,4
      diaminobutaneH2](2+) and [1,5-diaminopentaneH2](2+) result in divergent packing
      motifs for these cations, which causes a reorganization of N-H...O hydrogen
      bonding and variances in the [V2Te2O10]n(2n-) chain metrics. The application of
      the NCI method to this type of solid-state structure provides a direct method to
      elucidate the structural effects of weak noncovalent interactions. 

PMID- 25569170
TI  - A discrete transition zone organizes the topological and regulatory autonomy of
      the adjacent tfap2c and bmp7 genes.
AB  - Despite the well-documented role of remote enhancers in controlling developmental
      gene expression, the mechanisms that allocate enhancers to genes are poorly
      characterized. Here, we investigate the cis-regulatory organization of the locus
      containing the Tfap2c and Bmp7 genes in vivo, using a series of engineered
      chromosomal rearrangements. While these genes lie adjacent to one another, we
      demonstrate that they are independently regulated by distinct sets of enhancers,
      which in turn define non-overlapping regulatory domains. Chromosome conformation
      capture experiments reveal a corresponding partition of the locus in two distinct
      structural entities, demarcated by a discrete transition zone. The impact of
      engineered chromosomal rearrangements on the topology of the locus and the
      resultant gene expression changes indicate that this transition zone functionally
      organizes the structural partition of the locus, thereby defining enhancer-target
      gene allocation. This partition is, however, not absolute: we show that it allows
      competing interactions across it that may be non-productive for the competing
      gene, but modulate expression of the competed one. Altogether, these data
      highlight the prime role of the topological organization of the genome in long
      distance regulation of gene expression. 

PMID- 25569172
TI  - Century-scale methylome stability in a recently diverged Arabidopsis thaliana
      lineage.
AB  - There has been much excitement about the possibility that exposure to specific
      environments can induce an ecological memory in the form of whole-sale, genome
      wide epigenetic changes that are maintained over many generations. In the model
      plant Arabidopsis thaliana, numerous heritable DNA methylation differences have
      been identified in greenhouse-grown isogenic lines, but it remains unknown how
      natural, highly variable environments affect the rate and spectrum of such
      changes. Here we present detailed methylome analyses in a geographically
      dispersed A. thaliana population that constitutes a collection of near-isogenic
      lines, diverged for at least a century from a common ancestor. Methylome
      variation largely reflected genetic distance, and was in many aspects similar to
      that of lines raised in uniform conditions. Thus, even when plants are grown in
      varying and diverse natural sites, genome-wide epigenetic variation accumulates
      mostly in a clock-like manner, and epigenetic divergence thus parallels the
      pattern of genome-wide DNA sequence divergence. 

PMID- 25569174
TI  - Mechanistic insights into EGFR membrane clustering revealed by super-resolution
      imaging.
AB  - The clustering of membrane receptors such as EGFR is critical for various
      biological processes, for example cell signaling and tumorigenesis. However, the
      mechanism involved remains poorly understood. Here, we used a super resolution
      imaging technique, which has shattered the longstanding resolution barrier of
      light diffraction, to investigate the distribution of membrane EGFR on apical or
      basal surfaces of COS-7 cells and on the surface of suspended COS-7 cells. Our
      data show that more and larger EGFR clusters are detected on the apical surface
      in comparison with those on the basal surface and this difference is not affected
      by the EGFR activation state, whereas suspended COS-7 cells exhibit a moderate
      clustering state and a homogeneous distribution pattern, indicating that the
      external environment surrounding the cell membrane is the decisive factor in the
      EGFR clustering pattern. A dual-color dSTORM image reveals the significant
      colocalization of EGFR and lipid rafts; interestingly MbetaCD treatment leads to
      a dramatic decrease of the amount and size of EGFR clusters on both apical and
      basal surfaces, highlighting a key role of lipid rafts in EGFR cluster formation.
      Altogether, our results illustrate the distribution pattern of EGFR in polarized
      cells and uncover the essential role of lipid rafts in EGFR cluster maintenance. 

PMID- 25569175
TI  - Wearable devices as facilitators, not drivers, of health behavior change.

PMID- 25569173
TI  - The global regulatory architecture of transcription during the Caulobacter cell
      cycle.
AB  - Each Caulobacter cell cycle involves differentiation and an asymmetric cell
      division driven by a cyclical regulatory circuit comprised of four transcription
      factors (TFs) and a DNA methyltransferase. Using a modified global 5' RACE
      protocol, we globally mapped transcription start sites (TSSs) at base-pair
      resolution, measured their transcription levels at multiple times in the cell
      cycle, and identified their transcription factor binding sites. Out of 2726 TSSs,
      586 were shown to be cell cycle-regulated and we identified 529 binding sites for
      the cell cycle master regulators. Twenty-three percent of the cell cycle
      regulated promoters were found to be under the combinatorial control of two or
      more of the global regulators. Previously unknown features of the core cell cycle
      circuit were identified, including 107 antisense TSSs which exhibit cell cycle
      control, and 241 genes with multiple TSSs whose transcription levels often
      exhibited different cell cycle timing. Cumulatively, this study uncovered novel
      new layers of transcriptional regulation mediating the bacterial cell cycle. 

PMID- 25569176
TI  - Enzalutamide for treatment of CRPC: rationale for sequencing and potential
      clinical biomarker for resistance.
AB  - The androgen receptor (AR) is central to the initiation and progression of
      prostate cancer, even after castration. There has been some success in therapies
      targeting AR signaling which have been shown to extend survival in men with
      castration-resistant prostate cancer (CRPC). Enzalutamide is a potent AR
      antagonist that was initially approved in 2012 for men with CRPC who had
      previously failed chemotherapy treatment with docetaxel. Herein, we reviewed 2
      key manuscripts that have recently appeared in the New England Journal of
      Medicine regarding enzalutamide. The PREVAIL Phase 3 trial was designed to
      evaluate enzalutamide before chemotherapy in men with CRPC. The study illustrated
      that 65% of patients receiving enzalutamide had radiographic-progression free
      survival. There was a significant risk reduction of radiographic progression or
      death, compared with the placebo group. The enzalutamide group's median overall
      survival was 32.4 months vs. 30.2 months in the placebo group. 

PMID- 25569178
TI  - Raman spectroscopy and in situ Raman spectroelectrochemistry of isotopically
      engineered graphene systems.
AB  - CONSPECTUS: The special properties of graphene offer immense opportunities for
      applications to many scientific fields, as well as societal needs, beyond our
      present imagination. One of the important features of graphene is the relatively
      simple tunability of its electronic structure, an asset that extends the
      usability of graphene even further beyond present experience. A direct injection
      of charge carriers into the conduction or valence bands, that is, doping,
      represents a viable way of shifting the Fermi level. In particular,
      electrochemical doping should be the method of choice, when higher doping levels
      are desired and when a firm control of experimental conditions is needed. In this
      Account, we focus on the electrochemistry of graphene in combination with in situ
      Raman spectroscopy, that is, in situ Raman spectroelectrochemistry. Such a
      combination of methods is indeed very powerful, since Raman spectroscopy not only
      can readily monitor the changes in the doping level but also can give information
      on eventual stress or disorder in the material. However, when Raman spectroscopy
      is employed, one of its main strengths lies in the utilization of isotope
      engineering during the chemical vapor deposition (CVD) growth of the graphene
      samples. The in situ Raman spectroelectrochemical study of multilayered systems
      with smartly designed isotope compositions in individual layers can provide a
      plethora of knowledge about the mutual interactions (i) between the graphene
      layers themselves, (ii) between graphene layers and their directly adjacent
      environment (e.g., substrate or electrolyte), and (iii) between graphene layers
      and their extended environment, which is separated from the layer by a certain
      number of additional graphene layers. In this Account, we show a few examples of
      such studies, from monolayer to two-layer and three-layer specimens and
      considering both turbostratic and AB interlayer ordering. Furthermore, the
      concept and the method can be extended further beyond the three-layer systems,
      for example, to heterostructures containing other 2-D materials beyond graphene.
      Despite a great deal of important results being unraveled so far through the in
      situ spectroelectrochemistry of graphene based systems, many intriguing
      challenges still lie immediately ahead. For example, apart from the
      aforementioned 2-D heterostructures, a substantial effort should be put into a
      more detailed exploration of misoriented (twisted) bilayer or trilayer graphenes.
      Marching from the oriented, AB-stacked to AA-stacked, bilayers, every single
      angular increment of the twist between the layers creates a new system in terms
      of its electronic properties. Mapping those properties and interlayer
      interactions dependent on the twist angle represents a sizable task, yet the
      reward might be the path toward the realization of various types of advanced
      devices. And last but not least, understanding the electrochemistry of graphene
      paves the way toward a controlled and targeted functionalization of graphene
      through redox reactions, especially when equipped with the possibility of an
      instantaneous monitoring of the thus introduced changes to the electronic
      structure of the system.

PMID- 25569177
TI  - Parent-infant psychotherapy for improving parental and infant mental health.
AB  - BACKGROUND: Parent-infant psychotherapy (PIP) is a dyadic intervention that works
      with parent and infant together, with the aim of improving the parent-infant
      relationship and promoting infant attachment and optimal infant development. PIP
      aims to achieve this by targeting the mother's view of her infant, which may be
      affected by her own experiences, and linking them to her current relationship to
      her child, in order to improve the parent-infant relationship directly.
      OBJECTIVES: 1. To assess the effectiveness of PIP in improving parental and
      infant mental health and the parent-infant relationship.2. To identify the
      programme components that appear to be associated with more effective outcomes
      and factors that modify intervention effectiveness (e.g. programme duration,
      programme focus). SEARCH METHODS: We searched the following electronic databases
      on 13 January 2014: Cochrane Central Register of Controlled Trials (CENTRAL,
      2014, Issue 1), Ovid MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS Citation Index,
      Science Citation Index, ERIC, and Sociological Abstracts. We also searched the
      metaRegister of Controlled Trials, checked reference lists, and contacted study
      authors and other experts. SELECTION CRITERIA: Two review authors assessed study
      eligibility independently. We included randomised controlled trials (RCT) and
      quasi-randomised controlled trials (quasi-RCT) that compared a PIP programme
      directed at parents with infants aged 24 months or less at study entry, with a
      control condition (i.e. waiting-list, no treatment or treatment-as-usual), and
      used at least one standardised measure of parental or infant functioning. We also
      included studies that only used a second treatment group. DATA COLLECTION AND
      ANALYSIS: We adhered to the standard methodological procedures of The Cochrane
      Collaboration. We standardised the treatment effect for each outcome in each
      study by dividing the mean difference (MD) in post-intervention scores between
      the intervention and control groups by the pooled standard deviation. We
      presented standardised mean differences (SMDs) and 95% confidence intervals (CI)
      for continuous data, and risk ratios (RR) for dichotomous data. We undertook meta
      analysis using a random-effects model. MAIN RESULTS: We included eight studies
      comprising 846 randomised participants, of which four studies involved
      comparisons of PIP with control groups only. Four studies involved comparisons
      with another treatment group (i.e. another PIP, video-interaction guidance,
      psychoeducation, counselling or cognitive behavioural therapy (CBT)), two of
      these studies included a control group in addition to an alternative treatment
      group. Samples included women with postpartum depression, anxious or insecure
      attachment, maltreated, and prison populations. We assessed potential bias
      (random sequence generation, allocation concealment, incomplete outcome data,
      selective reporting, blinding of participants and personnel, blinding of outcome
      assessment, and other bias). Four studies were at low risk of bias in four or
      more domains. Four studies were at high risk of bias for allocation concealment,
      and no study blinded participants or personnel to the intervention. Five studies
      did not provide adequate information for assessment of risk of bias in at least
      one domain (rated as unclear).Six studies contributed data to the PIP versus
      control comparisons producing 19 meta-analyses of outcomes measured at post
      intervention or follow-up, or both, for the primary outcomes of parental
      depression (both dichotomous and continuous data); measures of parent-child
      interaction (i.e. maternal sensitivity, child involvement and parent engagement;
      infant attachment category (secure, avoidant, disorganised, resistant);
      attachment change (insecure to secure, stable secure, secure to insecure, stable
      insecure); infant behaviour and secondary outcomes (e.g. infant cognitive
      development). The results favoured neither PIP nor control for incidence of
      parental depression (RR 0.74, 95% CI 0.52 to 1.04, 3 studies, 278 participants,
      low quality evidence) or parent-reported levels of depression (SMD -0.22, 95% CI 
      0.46 to 0.02, 4 studies, 356 participants, low quality evidence). There were
      improvements favouring PIP in the proportion of infants securely attached at post
      intervention (RR 8.93, 95% CI 1.25 to 63.70, 2 studies, 168 participants, very
      low quality evidence); a reduction in the number of infants with an avoidant
      attachment style at post-intervention (RR 0.48, 95% CI 0.24 to 0.95, 2 studies,
      168 participants, low quality evidence); fewer infants with disorganised
      attachment at post-intervention (RR 0.32, 95% CI 0.17 to 0.58, 2 studies, 168
      participants, low quality evidence); and an increase in the proportion of infants
      moving from insecure to secure attachment at post-intervention (RR 11.45, 95% CI
      3.11 to 42.08, 2 studies, 168 participants, low quality evidence). There were no
      differences between PIP and control in any of the meta-analyses for the remaining
      primary outcomes (i.e. adverse effects), or secondary outcomes.Four studies
      contributed data at post-intervention or follow-up to the PIP versus alternative
      treatment analyses producing 15 meta-analyses measuring parent mental health
      (depression); parent-infant interaction (maternal sensitivity); infant attachment
      category (secure, avoidant, resistant, disorganised) and attachment change
      (insecure to secure, stable secure, secure to insecure, stable insecure); infant
      behaviour and infant cognitive development. None of the remaining meta-analyses
      of PIP versus alternative treatment for primary outcomes (i.e. adverse effects),
      or secondary outcomes showed differences in outcome or any adverse changes.We
      used the Grades of Recommendation, Assessment, Development and Evaluation Working
      Group (GRADE) approach to rate the overall quality of the evidence. For all
      comparisons, we rated the evidence as low or very low quality for parental
      depression and secure or disorganised infant attachment. Where we downgraded the
      evidence, it was because there was risk of bias in the study design or execution
      of the trial. The included studies also involved relatively few participants and
      wide CI values (imprecision), and, in some cases, we detected clinical and
      statistical heterogeneity (inconsistency). Lower quality evidence resulted in
      lower confidence in the estimate of effect for those outcomes. AUTHORS'
      CONCLUSIONS: Although the findings of the current review suggest that PIP is a
      promising model in terms of improving infant attachment security in high-risk
      families, there were no significant differences compared with no treatment or
      treatment-as-usual for other parent-based or relationship-based outcomes, and no
      evidence that PIP is more effective than other methods of working with parents
      and infants. Further rigorous research is needed to establish the impact of PIP
      on potentially important mediating factors such as parental mental health,
      reflective functioning, and parent-infant interaction.

PMID- 25569179
TI  - Chabazite: stable cation-exchanger in hyper alkaline concrete pore water.
AB  - To avoid impact on the environment, facilities for permanent disposal of
      hazardous waste adopt multibarrier design schemes. As the primary barrier very
      often consists of cement-based materials, two distinct aspects are essential for
      the selection of suitable complementary barriers: (1) selective sorption of the
      contaminants in the repository and (2) long-term chemical stability in
      hyperalkaline concrete-derived media. A multidisciplinary approach combining
      experimental strategies from environmental chemistry and materials science is
      therefore essential to provide a reliable assessment of potential candidate
      materials. Chabazite is typically synthesized in 1 M KOH solutions but also
      crystallizes in simulated young cement pore water, a pH 13 aqueous solution
      mainly containing K(+) and Na(+) cations. Its formation and stability in this
      medium was evaluated as a function of temperature (60 and 85  degrees C) over a
      timeframe of more than 2 years and was also asessed from a mechanistic point of
      view. Chabazite demonstrates excellent cation-exchange properties in simulated
      young cement pore water. Comparison of its Cs(+) cation exchange properties at pH
      8 and pH 13 unexpectedly demonstrated an increase of the KD with increasing pH.
      The combined results identify chabazite as a valid candidate for inclusion in
      engineered barriers for concrete-based waste disposal. 

PMID- 25569181
TI  - Effects of northbound long-haul international air travel on sleep quantity and
      subjective jet lag and wellness in professional Australian soccer players.
AB  - The current study examined the effects of 10-h northbound air travel across 1
      time zone on sleep quantity, together with subjective jet lag and wellness
      ratings, in 16 male professional Australian football (soccer) players. Player
      wellness was measured throughout the week before (home training week) and the
      week of (away travel week) travel from Australia to Japan for a preseason tour.
      Sleep quantity and subjective jet lag were measured 2 d before (Pre 1 and 2), the
      day of, and for 5 d after travel (Post 1-5). Sleep duration was significantly
      reduced during the night before travel (Pre 1; 4.9 [4.2-5.6] h) and night of
      competition (Post 2; 4.2 [3.7-4.7] h) compared with every other night (P<.01,
      d>0.90). Moreover, compared with the day before travel, subjective jet lag was
      significantly greater for the 5 d after travel (P<.05, d>0.90), and player
      wellness was significantly lower 1 d post-match (Post 3) than at all other time
      points (P<.05, d>0.90). Results from the current study suggest that sleep
      disruption, as a result of an early travel departure time (8 PM) and evening
      match (7:30 PM), and fatigue induced by competition had a greater effect on
      wellness ratings than long-haul air travel with a minimal time-zone change.
      Furthermore, subjective jet lag may have been misinterpreted as fatigue from
      sleep disruption and competition, especially by the less experienced players.
      Therefore, northbound air travel across 1 time zone from Australia to Asia
      appears to have negligible effects on player preparedness for subsequent training
      and competition.

PMID- 25569180
TI  - Tsetse GmmSRPN10 has anti-complement activity and is important for successful
      establishment of trypanosome infections in the fly midgut.
AB  - The complement cascade in mammalian blood can damage the alimentary tract of
      haematophagous arthropods. As such, these animals have evolved their own
      repertoire of complement-inactivating factors, which are inadvertently exploited
      by blood-borne pathogens to escape complement lysis. Unlike the bloodstream
      stages, the procyclic (insect) stage of Trypanosoma brucei is highly susceptible
      to complement killing, which is puzzling considering that a tsetse takes a
      bloodmeal every 2-4 days. In this study, we identified four tsetse (Glossina
      morsitans morsitans) serine protease inhibitors (serpins) from a midgut expressed
      sequence tag (EST) library (GmmSRPN3, GmmSRPN5, GmmSRPN9 and GmmSRPN10) and
      investigated their role in modulating the establishment of a T. brucei infection
      in the midgut. Although not having evolved in a common blood-feeding ancestor,
      all four serpins have an active site sharing remarkable homology with the human
      complement C1-inhibitor serpin, SerpinG1. RNAi knockdown of individual GmmSRPN9
      and GmmSRPN10 genes resulted in a significant decreased rate of infection by
      procyclic form T. brucei. Furthermore, recombinant GmmSRPN10 was both able to
      inhibit the activity of human complement-cascade serine proteases, C1s and Factor
      D, and to protect the in vitro killing of procyclic trypanosomes when incubated
      with complement-activated human serum. Thus, the secretion of serpins, which may
      be part of a bloodmeal complement inactivation system in tsetse, is used by
      procyclic trypanosomes to evade an influx of fresh trypanolytic complement with
      each bloodmeal. This highlights another facet of the complicated relationship
      between T. brucei and its tsetse vector, where the parasite takes advantage of
      tsetse physiology to further its chances of propagation and transmission. 

PMID- 25569182
TI  - Ligand-Independent Activation of Platelet-Derived Growth Factor Receptor beta
      during Human Immunodeficiency Virus-Transactivator of Transcription and Cocaine
      Mediated Smooth Muscle Hyperplasia.
AB  - Our previous study supports an additive effect of cocaine to human
      immunodeficiency virus infection in the development of pulmonary arteriopathy
      through enhancement of proliferation of pulmonary smooth muscle cells (SMCs),
      while also suggesting involvement of platelet-derived growth factor receptor
      (PDGFR) activation in the absence of further increase in PDGF-BB ligand. Redox
      related signaling pathways have been shown to regulate tyrosine kinase receptors
      independent of ligand binding, so we hypothesized that simultaneous treatment of
      SMCs with transactivator of transcription (Tat) and cocaine may be able to
      indirectly activate PDGFR through modulation of reactive oxygen species (ROS)
      without the need for PDGF binding. We found that blocking the binding of ligand
      using suramin or monoclonal IMC-3G3 antibody significantly reduced ligand-induced
      autophosphorylation of Y1009 without affecting ligand-independent
      transphosphorylation of Y934 residue on PDGFRbeta in human pulmonary arterial
      SMCs treated with both cocaine and Tat. Combined treatment of human pulmonary
      arterial SMCs with cocaine and Tat resulted in augmented production of superoxide
      radicals and hydrogen peroxide when compared with either treatment alone.
      Inhibition of this ROS generation prevented cocaine- and Tat-mediated Src
      activation and transphosphorylation of PDGFRbeta at Y934 without any changes in
      phosphorylation of Y1009, in addition to attenuation of smooth muscle
      hyperplasia. Furthermore, pretreatment with an Src inhibitor, PP2, also
      suppressed cocaine- and Tat-mediated enhanced Y934 phosphorylation and smooth
      muscle proliferation. Finally, we report total abrogation of cocaine- and Tat
      mediated synergistic increase in cell proliferation on inhibition of both ligand
      dependent and ROS/Src-mediated ligand-independent phosphorylation of PDGFRbeta. 

PMID- 25569184
TI  - Membrane tension and peripheral protein density mediate membrane shape
      transitions.
AB  - Endocytosis is a ubiquitous eukaryotic membrane budding, vesiculation and
      internalization process fulfilling numerous roles including compensation of
      membrane area increase after bursts of exocytosis. The mechanism of the coupling
      between these two processes to enable homeostasis is not well understood.
      Recently, an ultrafast endocytosis (UFE) pathway was revealed with a speed
      significantly exceeding classical clathrin-mediated endocytosis (CME). Membrane
      tension reduction is a potential mechanism by which endocytosis can be rapidly
      activated at remote sites. Here, we provide experimental evidence for a mechanism
      whereby membrane tension reduction initiates membrane budding and tubulation
      mediated by endocytic proteins, such as endophilin A1. We find that shape
      instabilities occur at well-defined membrane tensions and surface densities of
      endophilin. From our data, we obtain a membrane shape stability diagram that
      shows remarkable consistency with a quantitative model. This model applies to all
      laterally diffusive curvature-coupling proteins and therefore a wide range of
      endocytic proteins. 

PMID- 25569186
TI  - Identification of the minimum peptide from mouse myostatin prodomain for human
      myostatin inhibition.
AB  - Myostatin, an endogenous negative regulator of skeletal muscle mass, is a
      therapeutic target for muscle atrophic disorders. Here, we identified minimum
      peptides 2 and 7 to effectively inhibit myostatin activity, which consist of 24
      and 23 amino acids, respectively, derived from mouse myostatin prodomain. These
      peptides, which had the propensity to form alpha-helix structure, interacted to
      myostatin with KD values of 30-36 nM. Moreover, peptide 2 significantly increased
      muscle mass in Duchenne muscular dystrophy model mice. 

PMID- 25569188
TI  - Medication risk-taking behavior in functional dyspepsia patients.
AB  - OBJECTIVES: No medication is approved for the treatment of functional dyspepsia
      (FD). The risks that patients would be willing to take to cure their FD symptoms
      are unknown. METHODS: FD patients (Rome III criteria) were mailed a questionnaire
      that assessed demographics, medication use, and prior medication adverse events.
      Scales to measure FD severity, quality of life, anxiety, depression,
      impulsiveness, and risk-taking behavior were included. A standard gamble (SG)
      evaluated willingness to take risks associated with a theoretical FD medication.
      Data were analyzed using simple descriptive statistics. RESULTS: One hundred and
      fourteen responses were analyzed (54.5% response rate). The mean age of the
      patients was 49.2 years; 84% were women and 96% were white. The mean duration of
      symptoms was 8.2 years (range 1-38 years). The most bothersome symptom was upper
      abdominal discomfort (25%), followed by upper abdominal pain (22%) and bloating
      (15%). Forty percent of respondents rated their FD symptoms as moderate and 31%
      as mild. Forty-six percent reported a side effect from a prescription medication
      used to treat FD. When asked about a hypothetical medication that could cure
      their FD symptoms, 49% of respondents reported that they would accept a mean
      12.7% risk of sudden death for a 99% chance of cure. CONCLUSIONS: This
      prospective study suggests that FD patients are surprisingly willing to take
      significant risks with a hypothetical medication to cure their symptoms. To
      counsel patients effectively and assist in the development of informed,
      preference-based decisions regarding medication therapy, physicians need to
      elicit and understand FD patients' risk adversity.

PMID- 25569185
TI  - The use of beta2-agonist therapy before hospital attendance for severe asthma
      exacerbations: a post-hoc analysis.
AB  - BACKGROUND: Patterns of inhaled beta2-agonist therapy use during severe asthma
      exacerbations before hospital attendance are poorly understood. AIMS: To assess
      beta2-agonist use prior to hospital attendance. METHODS: We undertook an
      exploratory post hoc analysis of data from a 6-month clinical trial of 303
      patients randomised to combination budesonide/formoterol inhaler according to a
      Single combination inhaler as Maintenance And Reliever Therapy regimen ('SMART')
      or fixed-dose budesonide/formoterol with salbutamol as reliever ('Standard').
      Patterns of beta2-agonist use for 14 days before hospital attendance with a
      severe asthma exacerbation were determined by electronic monitoring of inhaler
      use. RESULTS: There were 22 hospital attendances in 16 patients during the study.
      Seven and nine hospital attendances were eligible for analysis in the SMART and
      Standard groups, respectively. In both regimens, beta2-agonist use increased
      before hospital attendance, with a median (range) maximum daily number of
      actuations of 14 (9 to 63) budesonide/formoterol in SMART and 46 (6 to 95)
      salbutamol in Standard with 4 (0 to 10) budesonide/formoterol actuations on the
      day of maximal salbutamol use. There was delay in obtaining medical review
      despite high beta2-agonist use, in 9/16 patients. Different patterns of use were
      observed, including repeated days of no inhaled corticosteroid despite marked
      salbutamol use, which occurred in 3/9 patients in the Standard group.
      CONCLUSIONS: Delay in obtaining medical review in association with high beta2
      agonist use is common in patients before hospital presentation with severe
      exacerbations of asthma. The SMART regimen reduced nonadherence with inhaled
      corticosteroid therapy during severe exacerbations.

PMID- 25569187
TI  - The Common Chymotrypsinogen C (CTRC) Variant G60G (C.180T) Increases Risk of
      Chronic Pancreatitis But Not Recurrent Acute Pancreatitis in a North American
      Population.
AB  - OBJECTIVES: Recurrent acute pancreatitis (RAP) is a complex inflammatory disorder
      that may progress to fibrosis and other irreversible features recognized as
      chronic pancreatitis (CP). Chymotrypsinogen C (CTRC) protects the pancreas by
      degrading prematurely activated trypsinogen. Rare mutations are associated with
      CP in Europe and Asia. We evaluated the occurrence of CTRC variants in subjects
      with RAP, CP, and controls from the North American Pancreatitis Study II cohort.
      METHODS: CP (n=694), RAP (n=448), and controls (n=1017) of European ancestry were
      evaluated. Subgroup analysis included CFTR and SPINK1 variants, alcohol, and
      smoking. RESULTS: We identified previously reported rare pathogenic CTRC A73T,
      R254W, and K247_R254del variants, intronic variants, and G60G (c.180 C>T;
      rs497078). Compared with controls (minor allele frequency (MAF)=10.8%), c.180T
      was associated with CP (MAF=16.8%, P<0.00001) but not RAP (MAF=11.9% P=NS). Trend
      test indicated co-dominant risk for CP (CT odds ratio (OR)=1.36, 95% confidence
      interval (CI)=1.13-1.64, P=0.0014; TT OR=3.98, 95% CI=2.10-7.56, P<0.0001). The T
      allele was significantly more frequent with concurrent pathogenic CFTR variants
      and/or SPINK1 N34S (combined 22.9% vs. 16.1%, OR 1.92, 95% C.I. 1.26-2.94,
      P=0.0023) and with alcoholic vs. non-alcoholic CP etiologies (20.8% vs. 12.4%,
      OR=1.9, 95% CI=1.30-2.79, P=0.0009). Alcohol and smoking generally occurred
      together, but the frequency of CTRC c.180 T in CP, but not RAP, was higher among
      never drinkers-ever smokers (22.2%) than ever drinker-never smokers (10.8%),
      suggesting that smoking rather than alcohol may be the driving factor in this
      association. CONCLUSIONS: The common CTRC variant c.180T acts as disease modifier
      that promotes progression from RAP to CP, especially in patients with CFTR or
      SPINK1 variants, alcohol, or smoking.

PMID- 25569190
TI  - Lung obstruction among adults aged 40-79: United States, 2007-2012.
AB  - During 2007-2012, 14.7% of U.S. adults aged 40-79 had lung obstruction, with
      almost two-thirds having mild lung obstruction (9.4%) and one-third having
      moderate or worse obstruction (5.3%). A similar percentage of men and women had
      any lung obstruction, a pattern that persisted at each level of severity. There
      were notable differences in lung obstruction by race and Hispanic origin. Overall
      and at both levels of severity, rates of lung obstruction were higher for non
      Hispanic white and non- Hispanic black adults compared with Hispanic adults.
      Overall and at the mild lung obstruction level, the percentage of non-Hispanic
      white adults with lung obstruction was significantly higher than that of non
      Hispanic black adults. Lung obstruction also varied by education level. Adults
      who had attended college had a significantly lower percentage of moderate or
      worse lung obstruction compared with adults with less education. Among adults
      with mild lung obstruction, percentages were similar by education level. More
      than one-half of adults aged 40-79 with lung obstruction reported having at least
      one respiratory symptom. Reporting rates for each symptom and for one or more
      symptoms were all higher for those adults with moderate or worse lung obstruction
      than for those with mild obstruction. Among adults with moderate or worse lung
      obstruction, more than 80% reported having at least one respiratory symptom.

PMID- 25569189
TI  - The inactivation of Staphylococcus aureus biofilms using low-power argon plasma
      in a layer-by-layer approach.
AB  - The direct application of low power argon plasma for the decontamination of pre
      formed Staphylococcus aureus biofilms on various surfaces was examined. Distinct
      chemical/physical properties of reactive species found in argon plasmas generated
      at different wattages all demonstrated very potent but very different anti
      biofilm mechanisms of action. An in-depth analysis of the results showed that:
      (1) the different reactive species produced in each plasma demonstrated specific
      antibacterial and/or anti-biofilm activity; and (2) the commonly associated
      etching effect could be manipulated and even controlled, depending on the
      experimental conditions. Under optimal experimental parameters, bacterial cells
      in S. aureus biofilms were killed (> 99.9%) by plasmas within 10 min of exposure
      and no bacteria nor biofilm regrowth from argon discharge gas treated biofilms
      was observed for 150 h. The decontamination ability of plasmas for the treatment
      of biofilm related contaminations on various materials was confirmed and an
      entirely novel layer-by-layer decontamination approach was designed and examined.

PMID- 25569183
TI  - A genome-wide association study of marginal zone lymphoma shows association to
      the HLA region.
AB  - Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non
      Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127
      controls of European ancestry and identify two independent loci near BTNL2
      (rs9461741, P=3.95 * 10(-15)) and HLA-B (rs2922994, P=2.43 * 10(-9)) in the HLA
      region significantly associated with MZL risk. This is the first evidence that
      genetic variation in the major histocompatibility complex influences MZL
      susceptibility. 

PMID- 25569191
TI  - A new combinatorial method for synthesizing, screening, and discovering
      antifouling surface chemistries.
AB  - A set of diverse monomers were synthesized using combinatorial chemistry and
      tested using our unique high-throughput screening platform. The versatility of
      our platform is exemplified by possible applications in reducing biological
      fouling on ship hulls, filtration membranes, and surgical instruments, to name a
      few. To demonstrate its efficacy, the novel monomers were graft-polymerized onto
      light sensitive poly(ether sulfone) (PES) membranes via atmospheric-pressure
      plasma polymerization. A diverse library was synthesized by reacting a common
      vinyl ester linker with a library of maleimides containing various different
      functional groups. This allowed us to produce a library of many different
      surfaces and graft them all using the same linker chemistry. The modified
      surfaces were then tested and screened for the best antiprotein adsorption
      (nonfouling) properties. Membranes, functionalized with carboxylic acid,
      zwitterionic, and ester groups, had the lowest protein adhesion compared with
      that of an unmodified control PES membrane after a static fouling test. After
      dynamic fouling, these same functionalities as well as a hydroxyl group exhibited
      the highest permeability. These monomers performed better than our best
      previously synthesized amide monomers as well as our best poly(ethylene glycol)
      monomers, which are known to have very high protein resistance. Hansen solubility
      parameters qualitatively predicted which monomers performed best, indicating
      favorable interactions with water molecules. 

PMID- 25569192
TI  - Purification and characterization of a novel lectin from Chinese leek seeds.
AB  - A novel lectin, CLSL, was purified from Chinese leek seeds by ion exchange
      chromatography on SP Sephadex C-25 and gel filtration chromatography on Sephadex
      G50. The lectin had a molecular weight of 23.6 kDa and was composed of two
      identical subunits linked by disulfide bonds, a conclusion based on SDS-PAGE
      under reducing and nonreducing conditions. CLSL was a glycoprotein with a
      carbohydrate content of 3.6%. It exerted potent agglutinating activity against
      rat red blood cells at a concentration of 8.9 MUg/mL. Hemagglutination of rat
      erythrocytes was inhibited by d-fructose, mannitol, and sorbose at the
      concentration of 20 mM. The hemagglutinating activity of CLSL was maintained at
      100  degrees C for 60 min and under acidic pH conditions but was lost at neutral
      and alkaline pH conditions. The hemagglutinating activity was stimulated by
      Ca(2+), Fe(2+), and Cu(2+) but inactivated by Ba(2+) at a concentration of 10 mM.
      Ba(2+)-mediated inactivation of CLSL was caused by CLSL conformational change
      induced by barium ions, according to the results of circular dichroism and
      fluorescence spectroscopy. Deconvolution of the CLSL circular dichroism indicated
      that it was an alpha-helical lectin with alpha-helix and beta-fold contents of
      35.8% and 8.6%, respectively. CLSL could also selectively inhibit cell
      proliferation.

PMID- 25569193
TI  - Spectroscopic study of the melting and reconstruction of sodium bis(2-ethylhexyl)
      sulfosuccinate (AOT) reverse micelles from their frozen states.
AB  - The confinement of water in organic self-assemblies with nanometer-sized pores is
      ubiquitous in nature. Water pools in sodium bis(2-ethylhexyl) sulfosuccinate
      (AOT) reverse micelles have been intensively studied as a representative model of
      such confined water. However, the freezing and melting behavior of such water
      pools is poorly understood owing to their poor structural stability under phase
      transition. In the present work, the melting of iced water pools accompanied by a
      reconstruction of AOT reverse micelles was studied with infrared spectroscopy.
      For all AOT reverse micelles tested (Rw: 1.2-4.4 nm), a characteristic ice-water
      coexistence phase was observed during melting. The results provide experimental
      evidence of the previously proposed core-shell structure of the water pool. For
      larger frozen reverse micelles (Rw>2.3 nm), shifts of the upsilon(OH) bands were
      observed. The spectra of the shifted upsilon(OH) bands were similar to those for
      the melted water pools in the smaller micelles. The mechanism of the
      reconstruction of AOT reverse micelles from their frozen states and the
      corresponding transient changes in the local environments were also discussed.

PMID- 25569194
TI  - Therapeutic effects of systemic vitamin k2 and vitamin d3 on gingival
      inflammation and alveolar bone in rats with experimentally induced periodontitis.
AB  - BACKGROUND: The synergistic effects of vitamin D3 and vitamin K2 on bone loss
      prevention have been reported. This study evaluates the effects of vitamin D3 and
      vitamin K2 supplementation in conjunction with conventional periodontal therapy
      (scaling and root planing [SRP]) on gingival interleukin (IL)-1beta and IL-10,
      serum bone alkaline phosphatase (B-ALP) and tartrate-resistant acid phosphatase
      5b (TRAP-5b), and calcium and alveolar bone levels in rats with experimentally
      induced periodontitis. METHODS: Seventy-two rats were divided into the following
      groups: 1) healthy; 2) periodontitis; 3) SRP; 4) SRP + vitamin D3; 5) SRP +
      vitamin K2; and 6) SRP + vitamins K2 and D3. Periodontitis was induced by
      ligature placement for 7 days, and vitamin K2 (30 mg/kg) and/or vitamin D3 (2
      MUg/kg) were administered for 10 days in the SRP + vitamin D3, SRP + vitamin K2,
      and SRP + vitamins K2 and D3 groups by oral gavage. On day 18, the animals were
      sacrificed, serum B-ALP, TRAP-5b, and calcium levels were measured, gingiva
      specimens were extracted for IL-1beta and IL-10 analysis, and distances between
      the cemento-enamel junction and alveolar bone crest were evaluated. RESULTS:
      Alveolar bone levels in the periodontitis group were significantly greater than
      those in the other five groups. No significant differences were found in gingival
      IL-1beta and IL-10, serum B-ALP and TRAP-5b, and calcium and alveolar bone levels
      between the groups receiving SRP and vitamins and the group receiving SRP alone.
      CONCLUSION: Within the limitations of this study, vitamin D3 and K2 alone or in
      combination did not affect gingival IL-1beta and IL-10, serum B-ALP and TRAP-5b
      levels, or alveolar bone compared with conventional periodontal therapy alone.

PMID- 25569195
TI  - Selective vascular isolation of the liver as part of initial damage control for
      grade 5 liver injuries: Shouldn't we use it more frequently?
AB  - BACKGROUND: Severe liver trauma (grade 4 and 5) carries mortality greater than
      40%. It represents a major surgical challenge in patients with hemodynamic
      instability who require an immediate exploratory laparotomy. Perihepatic packing
      and damage control can sometimes work, but for severe liver injuries, adjunct
      maneuvers might be needed (such as early embolization or hepatic artery
      ligation). During a patient's first operation for severe liver trauma, anatomic
      resection is rarely tolerated. MATERIALS AND METHODS: We managed a 31 year-old
      male with a blunt grade 5 right-lobe liver injury in severe hypovolemic shock.
      RESULTS: As part of the initial damage control operation, concurrently with
      intermittent Pringle maneuver, he underwent intra- and perihepatic packing;
      selective isolation and ligation of the right portal vein, right hepatic artery,
      and right hepatic vein; and repair of the retrohepatic inferior vena cava. Then,
      36h later, the patient underwent a right hepatectomy. CONCLUSION: For patients
      with severe liver injuries, selective vascular isolation and ligation may be
      considered as part of damage control (in addition to intermittent Pringle
      maneuver) and might enable anatomic resection at a later stage.

PMID- 25569196
TI  - Vertebral destruction due to abdominal aortic aneurysm.
AB  - INTRODUCTION: Low back pain is a common cause of medical consultation, and
      usually supposes a non-malignant prognostic. PRESENTATION OF CASE: We report an
      atypical appearance of low back pain associated to shock and pulsatile abdominal
      mass that made us diagnose an abdominal aortic aneurysm as reason of vertebral
      lysis and pain. DISCUSION: Surgical repair of contained AAA should be directed to
      secondary re-rupture prevention, with an approximate survival near to 100% at
      selected patients for elective surgery. Consequently, orthopedic surgery for back
      spine stabilization has to be elective in those cases when vertebral destruction
      is above 30% and clinic is directly related to spine instability. CONCLUSION: We
      should consider AAA as other cause of low back pain and routinely examine the
      abdomen and seek complementary imaging proves when risk factors for AAA are
      present.

PMID- 25569197
TI  - A rare case of tension pneumocephalus after head trauma.
AB  - OBJECTIVES: We present a rare case of tension pneumocephalus (TP) after head
      trauma not involving mask ventilation but based on pathological respiration
      pattern, kussmaul breathing. TP is rare condition and exceptionally rare when
      positive airway pressure has not been applied. In this particular case, the
      vacuum and one-valve intracranial effects causing pneumocephalon were instead
      accentuated by a pathological pattern of respiration due to severe ketoacidosis -
      a condition not previously reported in the literature. METHODS: This is a case
      report showing a rare cause of pneumocephalon caused by patients own respiration.
      We retrospectively reviewed the patients' journal to find the cause of his severe
      pneumocephalon. The patient has not been ventilated and the only cause of TP in
      this case seems to be his own rapid and pathological breathing caused by
      ketoacidosis. CONCLUSION: In the presented case, pathologic deep and rapid
      respiration exerted additional pressure on the dural fistula allowing ambient air
      at a pressure above ICP to drive itself into the intracranial space. The loss of
      CSF from skull base fractures created a void space and relative negative
      pressure, allowing air to bubble in and fill the void.

PMID- 25569198
TI  - Confirmation of 20% error in the (209)Po half-life.
AB  - First results of a half-life measurement of (209)Po show 20% discrepancy with the
      formerly recommended value of 102 (5) years, which was based on a single
      experiment performed in 1956. After one year of measurement, a statistical
      uncertainty on T1/2 of 3.5% has been reached and effects of long-term instability
      are assumed to be less than 5%. The preliminary half-life value obtained in this
      work, 120 (6) years, supports the newly determined value of 125.2 (33) years by
      Colle et al. (2014). The 20% error in the half-life has an impact on numerous
      measurements in which aged (209)Po solutions were used as a tracer. 

PMID- 25569199
TI  - Performance revaluation of a N-type coaxial HPGe detector with front edges
      crystal using MCNPX.
AB  - The MCNPX code was used to determine the efficiency of a N-type HPGe detector
      after two decades of operation. Accounting for the roundedness of the crystal's
      front edges and an inhomogeneous description of the detector's dead layers were
      shown to achieve better agreement between measurements and simulation efficiency
      determination. The calculations were experimentally verified using point sources
      in the energy range from 50keV to 1400keV, and an overall uncertainty less than
      2% was achieved. In order to use the detector for different matrices and
      geometries in radioactivity, the suggested model was validated by changing the
      counting geometry and by using multi-gamma disc sources. The introduced
      simulation approach permitted the revaluation of the performance of an HPGe
      detector in comparison of its initial condition, which is a useful tool for
      precise determination of the thickness of the inhomogeneous dead layer. 

PMID- 25569200
TI  - Set-up of a new TDCR counter at IRA-METAS.
AB  - A triple-to-double coincidence ratio (TDCR) counter was recently constructed at
      IRA-METAS for liquid scintillation based primary activity standardisations. A
      description of its optical chamber, efficiency change tools, photomultiplier
      tubes (PMTs) and electronics is given. This TDCR system was validated by
      measuring several standard solutions of beta emitters including (45)Ca, (14)C,
      (63)Ni and (3)H. The activity concentrations, obtained from these measurements
      and efficiencies computed with a FORTRAN code we developed for symmetric and
      asymmetric PMTs, agree with the certified values within uncertainties. 

PMID- 25569201
TI  - Temperature effect of a radioluminescent nuclear battery based on
      (147)Pm/ZnS:Cu/GaAs.
AB  - A radioluminescent nuclear battery was fabricated and the performance was
      measured and calculated at temperature of 223.15-323.15K. Experimental and
      theoretical results indicate that Jsc minimally decreases with the increase in
      temperature, whereas Voc linearly decreases. Pmax rapidly decreases with
      temperature. The mechanism of temperature effect is discussed using the
      temperature dependency of semiconductor parameters. This study significantly
      guides the selection of batteries' power source under various temperature. The
      nuclear battery may also be used as a long-life temperature transducer. 

PMID- 25569202
TI  - US Republicans will attack individual provisions of health reform law as repeal
      is unlikely.

PMID- 25569203
TI  - The political determinants of health--10 years on.

PMID- 25569205
TI  - N-Pyridineium-2-yl Darrow Red analogue: unique near-infrared lysosome-biomarker
      for the detection of cancer cells.
AB  - The lysosome-targetable OFF-ON type pH sensor that does not emit at pH = 4.0 is
      adopted for the selective detection of cancer cells, and the acidity difference
      of lysosomes in cancer and normal cells is verified. Three pH probes based on
      Darrow Red derivatives were designed and prepared that were demonstrated to be
      lysosome-specific biomarkers with inducible emission at 580-850 nm by the
      comparable in cellular imaging assays using HeLa, KB, and V79 cells. Of these, a
      pyridineium-2-yl Darrow Red analogue with a pKa of 2.4 was found to be a lysosome
      tracker for cancer cells, it is a unique pH sensor for the optical identification
      and distinction of cancer cells from normal cells and has potential application
      as a fluorescent biomaker of cancer cells in in vitro assays. 

PMID- 25569204
TI  - Prescription Drug Misuse and Sexual Behavior Among Young Adults.
AB  - Though research indicates a complex link between substance use and sexual risk
      behavior, there is limited research on the association between sexual risk
      behavior and prescription drug misuse. In light of alarming increases in
      prescription drug misuse and the role of demographic characteristics in sexual
      risk behavior and outcomes, the current study examined demographic differences
      (gender, sexual identity, age, relationship status, parental class background,
      and race/ethnicity) in sexual risk behavior, sexual behavior under the influence
      of prescription drugs, and sexual risk behavior under the influence of
      prescription drugs in a sample of 402 young adults (ages 18 to 29) who misused
      prescription drugs. Nearly half of the sexually active young adult prescription
      drug misusers in this sample reported recent sex under the influence of
      prescription drugs; more than three-quarters reported recent sex without a
      condom; and more than one-third reported recent sex without a condom after using
      prescription drugs. Zero-inflated Poisson regression models indicated that White
      race, younger age, higher parental class, and being a heterosexual man were all
      associated with sexual risk behavior, sex under the influence of prescription
      drugs, and sexual risk under the influence of prescription drugs. Findings have
      implications for the targeting of prevention and intervention efforts. 

PMID- 25569207
TI  - Google, doctors, and the "right to be forgotten".

PMID- 25569206
TI  - Quantifying and monitoring overdiagnosis in cancer screening: a systematic review
      of methods.
AB  - OBJECTIVE: To determine the optimal method for quantifying and monitoring
      overdiagnosis in cancer screening over time. DESIGN: Systematic review of primary
      research studies of any design that quantified overdiagnosis from screening for
      nine types of cancer. We used explicit criteria to critically appraise individual
      studies and assess strength of the body of evidence for each study design (double
      blinded review), and assessed the potential for each study design to accurately
      quantify and monitor overdiagnosis over time. DATA SOURCES: PubMed and Embase up
      to 28 February 2014; hand searching of systematic reviews. ELIGIBILITY CRITERIA
      FOR SELECTING STUDIES: English language studies of any design that quantified
      overdiagnosis for any of nine common cancers (prostate, breast, lung, colorectal,
      melanoma, bladder, renal, thyroid, and uterine); excluded case series, case
      reports, and reviews that only reported results of other studies. RESULTS: 52
      studies met the inclusion criteria. We grouped studies into four methodological
      categories: (1) follow-up of a well designed randomized controlled trial (n=3),
      which has low risk of bias but may not be generalizable and is not suitable for
      monitoring; (2) pathological or imaging studies (n=8), drawing conclusions about
      overdiagnosis by examining biological characteristics of cancers, a simple design
      limited by the uncertain assumption that the measured characteristics are highly
      correlated with disease progression; (3) modeling studies (n=21), which can be
      done in a shorter time frame but require complex mathematical equations
      simulating the natural course of screen detected cancer, the fundamental unknown
      question; and (4) ecological and cohort studies (n=20), which are suitable for
      monitoring over time but are limited by a lack of agreed standards, by variable
      data quality, by inadequate follow-up time, and by the potential for population
      level confounders. Some ecological and cohort studies, however, have addressed
      these potential weaknesses in reasonable ways. CONCLUSIONS: Well conducted
      ecological and cohort studies in multiple settings are the most appropriate
      approach for quantifying and monitoring overdiagnosis in cancer screening
      programs. To support this work, we need internationally agreed standards for
      ecological and cohort studies and a multinational team of unbiased researchers to
      perform ongoing analysis.

PMID- 25569208
TI  - Margaret McCartney: Jeremy Hunt should follow his own advice on emergency care.

PMID- 25569212
TI  - Atomic layer deposition of undoped TiO2 exhibiting p-type conductivity.
AB  - With prominent photocatalytic applications and widespread use in semiconductor
      devices, TiO2 is one of the most popular metal oxides. However, despite its
      popularity, it has yet to achieve its full potential due to a lack of effective
      methods for achieving p-type conductivity. Here, we show that undoped p-type TiO2
      films can be fabricated by atomic layer deposition (ALD) and that their
      electrical properties can be controlled across a wide range using proper
      postprocessing anneals in various ambient environments. Hole mobilities larger
      than 400 cm(2)/(V.s) are accessible superseding the use of extrinsic doping,
      which generally produces orders of magnitude smaller values. Through a
      combination of analyses and experiments, we provide evidence that this behavior
      is primarily due to an excess of oxygen in the films. This discovery enables
      entirely new categories of TiO2 devices and applications, and unlocks the
      potential to improve existing ones. TiO2 homojunction diodes fabricated
      completely by ALD are developed as a demonstration of the utility of these
      techniques and shown to exhibit useful rectifying characteristics even with
      minimal processing refinement. 

PMID- 25569211
TI  - Speech-like rhythm in a voiced and voiceless orangutan call.
AB  - The evolutionary origins of speech remain obscure. Recently, it was proposed that
      speech derived from monkey facial signals which exhibit a speech-like rhythm of
      ~5 open-close lip cycles per second. In monkeys, these signals may also be
      vocalized, offering a plausible evolutionary stepping stone towards speech. Three
      essential predictions remain, however, to be tested to assess this hypothesis'
      validity; (i) Great apes, our closest relatives, should likewise produce 5Hz
      rhythm signals, (ii) speech-like rhythm should involve calls articulatorily
      similar to consonants and vowels given that speech rhythm is the direct product
      of stringing together these two basic elements, and (iii) speech-like rhythm
      should be experience-based. Via cinematic analyses we demonstrate that an ex
      entertainment orangutan produces two calls at a speech-like rhythm, coined
      "clicks" and "faux-speech." Like voiceless consonants, clicks required no vocal
      fold action, but did involve independent manoeuvring over lips and tongue. In
      parallel to vowels, faux-speech showed harmonic and formant modulations, implying
      vocal fold and supralaryngeal action. This rhythm was several times faster than
      orangutan chewing rates, as observed in monkeys and humans. Critically, this
      rhythm was seven-fold faster, and contextually distinct, than any other known
      rhythmic calls described to date in the largest database of the orangutan
      repertoire ever assembled. The first two predictions advanced by this study are
      validated and, based on parsimony and exclusion of potential alternative
      explanations, initial support is given to the third prediction. Irrespectively of
      the putative origins of these calls and underlying mechanisms, our findings
      demonstrate irrevocably that great apes are not respiratorily, articulatorilly,
      or neurologically constrained for the production of consonant- and vowel-like
      calls at speech rhythm. Orangutan clicks and faux-speech confirm the importance
      of rhythmic speech antecedents within the primate lineage, and highlight
      potential articulatory homologies between great ape calls and human consonants
      and vowels. 

PMID- 25569210
TI  - Hyperreactive onchocerciasis is characterized by a combination of Th17-Th2 immune
      responses and reduced regulatory T cells.
AB  - Clinical manifestations in onchocerciasis range from generalized onchocerciasis
      (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease
      pathogenesis is associated with host inflammatory reactions, we investigated
      whether Th17 responses could be related to aggravated pathology in HO. Using flow
      cytometry, filarial-specific cytokine responses and PCR arrays, we compared the
      immune cell profiles, including Th subsets, in individuals presenting the two
      polar forms of infection and endemic normals (EN). In addition to elevated
      frequencies of memory CD4+ T cells, individuals with HO showed accentuated Th17
      and Th2 profiles but decreased CD4+CD25hiFoxp3+ regulatory T cells. These
      profiles included increased IL-17A+, IL-4+, RORC2+ and GATA3+CD4+ T cell
      populations. Flow cytometry data was further confirmed using a PCR array since
      Th17-related genes (IL-17 family members, IL-6, IL-1beta and IL-22) and Th2
      related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO
      individuals. In addition, stronger Onchocerca volvulus-specific Th2 responses,
      especially IL-13, were observed in vitro in hyperreactive individuals when
      compared to GEO or EN groups. This study provides initial evidence that elevated
      frequencies of Th17 and Th2 cells form part of the immune network instigating the
      development of severe onchocerciasis. 

PMID- 25569213
TI  - Pathology of the gallbladder in a child with metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage
      disease caused by deficient activity of arylsulfatase A, leading to an
      accumulation of sulfatide in myelinating cells and progressive central and
      peripheral demyelination. Sulfatide also accumulates in various organs, most
      notably the gallbladder. Gallbladder mucosal hyperplasia with papillomatosis, in
      the setting of abdominal pain and hemobilia, is often demonstrated by sonography.
      We present a histologic and ultrastructural description of these alterations in a
      5-year-old girl with MLD who presented with abdominal pain and feeding
      intolerance. Gross and light microscopic analysis demonstrated diffuse villous
      hyperplasia of the gallbladder mucosa with intraepithelial and intravillous
      macrophage accumulations of metachromatic material. Electron microscopic analysis
      demonstrated this material to comprise numerous membrane-bound inclusions
      composed of concentrically lamellated, dense material. The rarity of descriptions
      of this finding prompted this case report. 

PMID- 25569209
TI  - End of the beginning: elongation and termination features of alternative modes of
      chromosomal replication initiation in bacteria.
AB  - In bacterial cells, bidirectional replication of the circular chromosome is
      initiated from a single origin (oriC) and terminates in an antipodal terminus
      region such that movement of the pair of replication forks is largely
      codirectional with transcription. The terminus region is flanked by discrete Ter
      sequences that act as polar, or direction-dependent, arrest sites for fork
      progression. Alternative oriC-independent modes of replication initiation are
      possible, one of which is constitutive stable DNA replication (cSDR) from
      transcription-associated RNA-DNA hybrids or R-loops. Here, I discuss the
      distinctive attributes of fork progression and termination associated with
      different modes of bacterial replication initiation. Two hypothetical models are
      proposed: that head-on collisions between pairs of replication forks, which are a
      feature of replication termination in all kingdoms of life, provoke bilateral
      fork reversal reactions; and that cSDR is characterized by existence of distinct
      subpopulations in bacterial cultures and a widespread distribution of origins in
      the genome, each with a small firing potential. Since R-loops are known to exist
      in eukaryotic cells and to inflict genome damage in G1 phase, it is possible that
      cSDR-like events promote aberrant replication initiation even in eukaryotes. 

PMID- 25569214
TI  - Direct generation of oxygen-stabilized radicals by H* transfer from transition
      metal hydrides.
AB  - Transition-metal hydrides generate alpha-alkoxy radicals by H* transfer to enol
      ethers. We have measured the rate constant for transfer from CpCr(CO)3H to n
      butyl vinyl ether and have examined the chemistry of radicals generated by such
      transfers. Radicals from appropriate substrates undergo 5-exo cyclization, with
      higher diastereoselectivity than the analogous all-carbon radicals. From such
      radicals it is straightforward to make substituted tetrahydrofurans. 

PMID- 25569215
TI  - Chemo- and stereoselective synthesis of fluorinated enamides from ynamides in
      HF/pyridine: second-generation approach to potent ureas bioisosteres.
AB  - (E)- and (Z)-alpha-fluoroenamides could be easily prepared with high levels of
      chemo- and regioselectivities by hydrofluorination of readily available ynamides
      with HF/pyridine. The scope and limitations of this new process for the
      hydrofluorination of ynamides, as well as the stability of the resulting alpha
      fluoroenamides, have been extensively studied. Theoretical calculations at the
      MP2 and B3LYP levels of theory showed that the resulting fluoroenamides exhibit
      geometrical and electronic properties that partially mirror those of ureas,
      therefore demonstrating that the hydrofluorination of ynamides provides a
      general, straightforward, and user-friendly approach to bioisosteres of ureas,
      potent building blocks for biological studies and medicinal chemistry. 

PMID- 25569217
TI  - Virus-induced NETs--critical component of host defense or pathogenic mediator?

PMID- 25569216
TI  - Early virus-host interactions dictate the course of a persistent infection.
AB  - Many persistent viral infections are characterized by a hypofunctional T cell
      response and the upregulation of negative immune regulators. These events occur
      days after the initiation of infection. However, the very early host-virus
      interactions that determine the establishment of viral persistence remain poorly
      uncharacterized. Here we show that to establish persistence, LCMV must counteract
      an innate anti-viral immune response within eight hours after infection. While
      the virus triggers cytoplasmic RNA sensing pathways soon after infection, LCMV
      counteracts this pathway through a rapid increase in viral titers leading to a
      dysfunctional immune response characterized by a high cytokine and chemokine
      expression profile. This altered immune environment allows for viral replication
      in the splenic white pulp as well as infection of immune cells essential to an
      effective anti-viral immune response. Our findings illustrate how early events
      during infection critically dictate the characteristics of the immune response to
      infection and facilitate either virus control and clearance or persistence. 

PMID- 25569219
TI  - Adverse Events Related to Acupuncture: Development and Testing of a Rating Scale.
AB  - OBJECTIVES: Mild adverse events (AEs) are common with acupuncture, but the
      collection of AEs is generally poor. The objective of this study was to develop
      and test a new instrument for acupuncture-related AEs. MATERIALS AND METHODS:
      After literature review, consultation with experts, and pilot-testing, the
      acupuncture-related AE report form (AcupAE), a 20-item scale on local and
      systemic AEs was tested in 150 adults who were randomized to receive acupuncture,
      minimal acupuncture, and placebo acupuncture. AE was assessed using open-ended
      questioning, followed by the AcupAE after the third, sixth, and ninth treatment.
      RESULTS: The incidence of any AEs per patient, as derived from the AcupAE, was
      42.4% with acupuncture, 42.2% with minimal acupuncture, and 16.7% with placebo
      acupuncture; the respective incidence was 6.8%, 5.1%, and 3.3% with open-ended
      questioning. There was a significant difference in the incidence of any AEs
      between the 3 groups based on the AcupAE, and the incidence rates of any AEs were
      significantly higher when assessed by the AcupAE than by open-ended questioning
      in the acupuncture and minimal acupuncture groups. DISCUSSION: The AcupAE was
      able to detect differences in AE between true, minimal, and simulated
      acupuncture, whereas the open-ended questioning was not sensitive enough. The
      results support the use of AcupAE as an effective instrument for the assessment
      of acupuncture-related AEs. Although the checklist approach can result in
      overreporting and the causality may be unclear for some events, it is the first
      step for collecting standardized information and allowing comparison between
      different acupuncture approaches and patient groups in future studies.

PMID- 25569218
TI  - A Case-controlled Investigation of Pain Experience and Sensory Function in
      Neuronal Ceroid Lipofuscinosis.
AB  - OBJECTIVES: This case-control study explored pain experience and expression among
      individuals with neuronal ceroid lipofuscinosis (NCL) through parental report,
      tactile sensory testing, and infrared thermography (IRT). MATERIALS AND METHODS:
      Participants with NCL (n=8; M=14.8 y) and their unaffected siblings (n=8; M=23.5
      y) were characterized in terms of pain response to a brief tactile sensory test
      (light touch, Von Frey monofilament). During sensory testing, behavioral
      expression was measured using the Battens Observational Pain Scale and infrared
      thermography (IRT) was used to quantify changes in skin/eye temperature. RESULTS:
      Children with NCL experienced pain frequently and from multiple sources that
      negatively impacted their lives. Children with NCL were reactive to the sensory
      testing as indexed by significant increased IRT temperature change (P<0.001).
      Across combined sensory conditions, individuals with NCL were significantly more
      reactive (Battens Observational Pain Scale total score) to sensory testing
      compared with siblings (P<0.05). Similarly, IRT difference scores between sensory
      conditions revealed a significant increase in temperature for individuals with
      NCL compared with siblings (P<0.001). DISCUSSION: Ongoing reported pain was a
      problem for the children with NCL in this sample. Increased pain expression
      during the repeated Von Frey filament suggests that the pathophysiology of the
      ongoing pain may be centrally mediated.

PMID- 25569221
TI  - A RESTful API for accessing microbial community data for MG-RAST.
AB  - Metagenomic sequencing has produced significant amounts of data in recent years.
      For example, as of summer 2013, MG-RAST has been used to annotate over 110,000
      data sets totaling over 43 Terabases. With metagenomic sequencing finding even
      wider adoption in the scientific community, the existing web-based analysis tools
      and infrastructure in MG-RAST provide limited capability for data retrieval and
      analysis, such as comparative analysis between multiple data sets. Moreover,
      although the system provides many analysis tools, it is not comprehensive. By
      opening MG-RAST up via a web services API (application programmers interface) we
      have greatly expanded access to MG-RAST data, as well as provided a mechanism for
      the use of third-party analysis tools with MG-RAST data. This RESTful API makes
      all data and data objects created by the MG-RAST pipeline accessible as JSON
      objects. As part of the DOE Systems Biology Knowledgebase project (KBase,
      http://kbase.us) we have implemented a web services API for MG-RAST. This API
      complements the existing MG-RAST web interface and constitutes the basis of
      KBase's microbial community capabilities. In addition, the API exposes a
      comprehensive collection of data to programmers. This API, which uses a RESTful
      (Representational State Transfer) implementation, is compatible with most
      programming environments and should be easy to use for end users and third
      parties. It provides comprehensive access to sequence data, quality control
      results, annotations, and many other data types. Where feasible, we have used
      standards to expose data and metadata. Code examples are provided in a number of
      languages both to show the versatility of the API and to provide a starting point
      for users. We present an API that exposes the data in MG-RAST for consumption by
      our users, greatly enhancing the utility of the MG-RAST service. 

PMID- 25569222
TI  - A novel one-pot method for the synthesis of substituted furopyridines: iodine
      mediated oxidation of enaminones by tandem metal-free cyclization.
AB  - A novel iodine-mediated oxidative tandem cyclization reaction of simple
      enaminones has been developed for the synthesis of substituted furopyridines
      through C-C/C-N/C-O bond formation in a one-pot procedure. Substituted
      furopyridines are obtained in moderate to good yield. In addition, I- and Br
      substituted furopyridines have been successfully produced by the electrophilic
      substitution of N-iodo- or N-bromosuccinimide. 

PMID- 25569220
TI  - A Cross-sectional Examination of Vitamin D, Obesity, and Measures of Pain and
      Function in Middle-aged and Older Adults With Knee Osteoarthritis.
AB  - OBJECTIVES: The prevalence of knee osteoarthritis (OA) is increasing with the
      aging population and is exacerbated by the growing numbers of obese older adults.
      Low levels of vitamin D, measured by serum 25-hydroxyvitamin D (25(OH)D), in
      older adults and obese individuals are correlated with several negative health
      conditions, including chronic pain. This cross-sectional study sought to examine
      the interactive influence of 25(OH)D levels and obesity on knee OA pain and
      functional performance measures. METHODS: The sample consisted of 256 (63%
      female) racially diverse (55% black/African Americans) middle-aged and older
      adults (mean age 56.8 y). Blood was collected for analysis of 25(OH)D by high
      performance liquid chromatography. Participants provided self-report regarding
      knee OA pain and underwent a lower extremity functional performance test.
      RESULTS: Results demonstrated that obesity was associated with lower levels of
      25(OH)D. Participants with adequate 25(OH)D levels reported significantly less
      knee OA pain compared with participants with deficient or insufficient levels,
      regardless of obesity status. Furthermore, there was a significant interaction
      between obesity and 25(OH)D levels for lower extremity functional performance,
      such that obese individuals with adequate 25(OH)D levels demonstrated better
      performance than those obese participants with deficient or insufficient 25(OH)D
      levels. DISCUSSION: The mechanisms by which adequate 25(OH)D levels are
      associated with pain severity and improved function have not been completely
      elucidated. It may be that the pleiotropic role of biologically active 25(OH)D
      influences pain and pain processing through peripheral and central mechanisms.
      Alternatively, higher levels of pain may lead to reduced outdoor activity, which
      may contribute to both obesity and decreased vitamin D. Thus, investigating
      vitamin D status in obese and nonobese individuals with knee OA warrants further
      study.

PMID- 25569223
TI  - Blood gene signature for early hepatocellular carcinoma detection in patients
      with chronic hepatitis B.
AB  - PURPOSE: Up to 25% of chronic hepatitis B (CHB) patients eventually develop
      hepatocellular carcinoma (HCC), a disease with poor prognosis unless detected
      early. This study identifies a blood-based RNA biomarker panel for early HCC
      detection in CHB. MATERIALS AND METHODS: A genome-wide RNA expression study was
      performed using RNA extracted from blood samples from Malaysian patients (matched
      HCC, CHB, controls). Genes differentiating HCC from controls were selected for
      further testing using quantitative real-time polymerase chain reaction. Finally,
      a 6-gene biomarker panel was identified and characterized using a training set
      (cohort I = 126), and tested against 2 test sets (cohort II = 222; cohort III =
      174). The total number of samples used for each group is: HCC + CHB = 143, CHB =
      211, control = 168. RESULTS: Our gene panel displays a consistent trend
      distinguishing HCC from controls in our test sets, with an area under receiver
      operating characteristic curve of 0.9 in cohort III. Our independent test set
      (cohort III) showed that the gene panel had a sensitivity of 70% with a
      specificity of 92%. The biomarker profile for HCC was consistently detected in a
      small subgroup of CHB patients, thus potentially predicting early, preclinical
      cases of cancer that should be screened more intensively. CONCLUSION: The
      biomarkers identified in this study can be used as the basis of a blood-based
      test for the detection of early HCC in CHB.

PMID- 25569224
TI  - Endoscopic ultrasound in the evaluation of chronic upper abdominal pain of
      unknown etiology: a retrospective chart review examining the efficacy of EUS in
      determining a new diagnosis.
AB  - GOALS: To explore the utility of endoscopic ultrasound (EUS) in the evaluation of
      chronic upper abdominal pain (UAP) of undetermined etiology. BACKGROUND: Chronic
      UAP is a common problem with a challenging diagnosis and management. The role of
      EUS in the diagnosis of UAP may minimize additional testing; however, few studies
      describe the percentage of new diagnoses yielded in these patients. STUDY: We
      conducted a retrospective analysis by reviewing electronic medical records at
      Scott and White Memorial Hospital, Texas A&M Health Sciences Center for patients
      with abdominal pain for >= 12 months not explained by previous workup referred
      for EUS for chronic UAP from January 1, 1998 through October 1, 2007. Patients
      with previous EUS in past 12 months were excluded from the study. Patient
      demographic data and imaging performed 6 months before and 24 months after EUS
      were reviewed and results documented. RESULTS: EUS was successful at diagnosing a
      new clinical etiology of chronic UAP in 33 patients (8.89%) with previous workup
      that was unrevealing for a definitive diagnosis. The most frequent diagnoses
      included pancreaticobiliary tree abnormalities, chronic pancreatitis, and fatty
      liver disease. CONCLUSIONS: Our results support the fact that the majority of
      patients UAP with prior imaging will have no identifiable organic etiology found
      on EUS to explain their pain; however, we suggest that EUS be considered in
      patients with suspected pancreatic or biliary pathology.

PMID- 25569226
TI  - Water-processable laponite/polyaniline/graphene oxide nanocomposites for energy
      applications.
AB  - Graphene-polyaniline (GP) nanocomposites have demonstrated remarkable ability as
      supercapacitive materials and are typically synthesized via chemical reduction of
      graphene oxide/polyaniline (GOP) precursors. We report the formation of novel
      nanomaterials combining GOP nanocomposites with Laponite nanodisks. Host-guest
      interactions within GOP systems were studied with and without Laponite
      nanoparticle templating agents. Incorporating Laponite clay into the composite
      synthesis enhances aqueous dispersibility as well as facilitates the casting of
      homogeneous films. Structural and morphological characterization confirmed porous
      heterointerfaces and control of polymer and nanoclay loading. These results may
      enable the development of flexible supercapacitive and solar nanocomposites with
      improved device utility, water dispersibility, and film processability. We
      demonstrate that these films can be easily cast and that the composites maintain
      their electrical transport properties. 

PMID- 25569225
TI  - Redox state of flavin adenine dinucleotide drives substrate binding and product
      release in Escherichia coli succinate dehydrogenase.
AB  - The Complex II family of enzymes, comprising respiratory succinate dehydrogenases
      and fumarate reductases, catalyzes reversible interconversion of succinate and
      fumarate. In contrast to the covalent flavin adenine dinucleotide (FAD) cofactor
      assembled in these enzymes, soluble fumarate reductases (e.g., those from
      Shewanella frigidimarina) that assemble a noncovalent FAD cannot catalyze
      succinate oxidation but retain the ability to reduce fumarate. In this study, an
      SdhA-H45A variant that eliminates the site of the 8alpha-N3-histidyl covalent
      linkage between the protein and FAD was examined. Variants SdhA-R286A/K/Y and 
      H242A/Y that target residues thought to be important for substrate binding and
      catalysis were also studied. The variants SdhA-H45A and -R286A/K/Y resulted in
      the assembly of a noncovalent FAD cofactor, which led to a significant decrease (
      87 mV or more) in its reduction potential. The variant enzymes were studied by
      electron paramagnetic resonance spectroscopy following stand-alone reduction and
      potentiometric titrations. The "free" and "occupied" states of the active site
      were linked to the reduced and oxidized states of FAD, respectively. Our data
      allow for a proposed model of succinate oxidation that is consistent with tunnel
      diode effects observed in the succinate dehydrogenase enzyme and a preference for
      fumarate reduction catalysis in fumarate reductase homologues that assemble a
      noncovalent FAD. 

PMID- 25569227
TI  - Brain network adaptability across task states.
AB  - Activity in the human brain moves between diverse functional states to meet the
      demands of our dynamic environment, but fundamental principles guiding these
      transitions remain poorly understood. Here, we capitalize on recent advances in
      network science to analyze patterns of functional interactions between brain
      regions. We use dynamic network representations to probe the landscape of brain
      reconfigurations that accompany task performance both within and between four
      cognitive states: a task-free resting state, an attention-demanding state, and
      two memory-demanding states. Using the formalism of hypergraphs, we identify the
      presence of groups of functional interactions that fluctuate coherently in
      strength over time both within (task-specific) and across (task-general) brain
      states. In contrast to prior emphases on the complexity of many dyadic (region-to
      region) relationships, these results demonstrate that brain adaptability can be
      described by common processes that drive the dynamic integration of cognitive
      systems. Moreover, our results establish the hypergraph as an effective measure
      for understanding functional brain dynamics, which may also prove useful in
      examining cross-task, cross-age, and cross-cohort functional change. 

PMID- 25569228
TI  - Host-seeking behavior and dispersal of Triatoma infestans, a vector of Chagas
      disease, under semi-field conditions.
AB  - Chagas disease affects millions of people in Latin America. The control of this
      vector-borne disease focuses on halting transmission by reducing or eliminating
      insect vector populations. Most transmission of Trypanosoma cruzi, the causative
      agent of Chagas disease, involves insects living within or very close to
      households and feeding mostly on domestic animals. As animal hosts can be
      intermittently present it is important to understand how host availability can
      modify transmission risk to humans and to characterize the host-seeking dispersal
      of triatomine vectors on a very fine scale. We used a semi-field system with
      motion-detection cameras to characterize the dispersal of Triatoma infestans, and
      compare the behavior of vector populations in the constant presence of hosts
      (guinea pigs), and after the removal of the hosts. The emigration rate - net
      insect population decline in original refuge - following host removal was on
      average 19.7% of insects per 10 days compared to 10.2% in constant host
      populations (p = 0.029). However, dispersal of T. infestans occurred in both
      directions, towards and away from the initial location of the hosts. The majority
      of insects that moved towards the original location of guinea pigs remained there
      for 4 weeks. Oviposition and mortality were observed and analyzed in the context
      of insect dispersal, but only mortality was higher in the group where animal
      hosts were removed (p-value <0.01). We discuss different survival strategies
      associated with the observed behavior and its implications for vector control.
      Removing domestic animals in infested areas increases vector dispersal from the
      first day of host removal. The implications of these patterns of vector dispersal
      in a field setting are not yet known but could result in movement towards human
      rooms. 

PMID- 25569230
TI  - Shaping the research agenda.

PMID- 25569231
TI  - Neck mass with progressive shortness of breath. Riedel sclerosing thyroiditis.

PMID- 25569229
TI  - mir-233 modulates the unfolded protein response in C. elegans during Pseudomonas
      aeruginosa infection.
AB  - The unfolded protein response (UPR), which is activated by perturbations of the
      endoplasmic reticulum homeostasis, has been shown to play an important role in
      innate immunity and inflammation. However, little is known about the molecular
      mechanisms underlying activation of the UPR during immune responses. Using small
      RNA deep sequencing and reverse genetic analysis, we show that the microRNA mir
      233 is required for activation of the UPR in Caenorhabditis elegans exposed to
      Pseudomonas aeruginosa PA14. P. aeruginosa infection up-regulates the expression
      of mir-233 in a p38 MAPK-dependent manner. Quantitative proteomic analysis
      identifies SCA-1, a C. elegans homologue of the sarco/endoplasmic reticulum Ca2+
      ATPase, as a target of mir-233. During P. aeruginosa PA14 infection, mir-233
      represses the protein levels of SCA-1, which in turn leads to activation of the
      UPR. Whereas mir-233 mutants are more sensitive to P. aeruginosa infection,
      knockdown of sca-1 leads to enhanced resistance to the killing by P. aeruginosa.
      Our study indicates that microRNA-dependent pathways may have an impact on innate
      immunity by activating the UPR. 

PMID- 25569232
TI  - Strengthening research capacity--TDR's evolving experience in low- and middle
      income countries.

PMID- 25569233
TI  - The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway.
AB  - Human BCL7 gene family consists of BCL7A, BCL7B, and BCL7C. A number of clinical
      studies have reported that BCL7 family is involved in cancer incidence,
      progression, and development. Among them, BCL7B, located on chromosome 7q11.23,
      is one of the deleted genes in patients with Williams-Beuren syndrome. Although
      several studies have suggested that malignant diseases occurring in patients with
      Williams-Beuren syndrome are associated with aberrations in BCL7B, little is
      known regarding the function of this gene at the cellular level. In this study,
      we focused on bcl-7, which is the only homolog of BCL7 gene family in
      Caenorhabditis elegans, and analyzed bcl-7 deletion mutants. As a result, we
      found that bcl-7 is required for the asymmetric differentiation of epithelial
      seam cells, which have self-renewal properties as stem cells and divide
      asymmetrically through the WNT pathway. Distal tip cell development, which is
      regulated by the WNT pathway in Caenorhabditis elegans, was also affected in bcl
      7-knockout mutants. Interestingly, bcl-7 mutants exhibited nuclear enlargement,
      reminiscent of the anaplastic features of malignant cells. Furthermore, in
      KATOIII human gastric cancer cells, BCL7B knockdown induced nuclear enlargement,
      promoted the multinuclei phenotype and suppressed cell death. In addition, this
      study showed that BCL7B negatively regulates the Wnt-signaling pathway and
      positively regulates the apoptotic pathway. Taken together, our data indicate
      that BCL7B/BCL-7 has some roles in maintaining the structure of nuclei and is
      involved in the modulation of multiple pathways, including Wnt and apoptosis.
      This study may implicate a risk of malignancies with BCL7B-deficiency, such as
      Williams-Beuren syndrome. 

PMID- 25569236
TI  - Reasons to be cautious about competing interests.

PMID- 25569234
TI  - Integrative analysis of DNA methylation and gene expression data identifies EPAS1
      as a key regulator of COPD.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a complex disease. Genetic,
      epigenetic, and environmental factors are known to contribute to COPD risk and
      disease progression. Therefore we developed a systematic approach to identify key
      regulators of COPD that integrates genome-wide DNA methylation, gene expression,
      and phenotype data in lung tissue from COPD and control samples. Our integrative
      analysis identified 126 key regulators of COPD. We identified EPAS1 as the only
      key regulator whose downstream genes significantly overlapped with multiple genes
      sets associated with COPD disease severity. EPAS1 is distinct in comparison with
      other key regulators in terms of methylation profile and downstream target genes.
      Genes predicted to be regulated by EPAS1 were enriched for biological processes
      including signaling, cell communications, and system development. We confirmed
      that EPAS1 protein levels are lower in human COPD lung tissue compared to non
      disease controls and that Epas1 gene expression is reduced in mice chronically
      exposed to cigarette smoke. As EPAS1 downstream genes were significantly enriched
      for hypoxia responsive genes in endothelial cells, we tested EPAS1 function in
      human endothelial cells. EPAS1 knockdown by siRNA in endothelial cells impacted
      genes that significantly overlapped with EPAS1 downstream genes in lung tissue
      including hypoxia responsive genes, and genes associated with emphysema severity.
      Our first integrative analysis of genome-wide DNA methylation and gene expression
      profiles illustrates that not only does DNA methylation play a 'causal' role in
      the molecular pathophysiology of COPD, but it can be leveraged to directly
      identify novel key mediators of this pathophysiology. 

PMID- 25569237
TI  - Characterization of RNA-Like Oligomers from Lipid-Assisted Nonenzymatic
      Synthesis: Implications for Origin of Informational Molecules on Early Earth.
AB  - Prebiotic polymerization had to be a nonenzymatic, chemically driven process.
      These processes would have been particularly favored in scenarios which push
      reaction regimes far from equilibrium. Dehydration-rehydration (DH-RH) cycles are
      one such regime thought to have been prevalent on prebiotic Earth in niches like
      volcanic geothermal pools. The present study defines the optimum DH-RH reaction
      conditions for lipid-assisted polymerization of nucleotides. The resultant
      products were characterized to understand their chemical makeup. Primarily, our
      study demonstrates that the resultant RNA-like oligomers have abasic sites, which
      means these oligomers lack information-carrying capability because of losing most
      of their bases during the reaction process. This results from low pH and high
      temperature conditions, which, importantly, also allows the formation of sugar
      phosphate oligomers when ribose 5'-monophosphates are used as the starting
      monomers instead. Formation of such oligomers would have permitted sampling of a
      large variety of bases on a preformed polymer backbone, resulting in "prebiotic
      phosphodiester polymers" prior to the emergence of modern RNA-like molecules.
      This suggests that primitive genetic polymers could have utilized bases that
      conferred greater N-glycosyl bond stability, a feature crucial for information
      propagation in low pH and high temperature regimes of early Earth. 

PMID- 25569235
TI  - Insight in genome-wide association of metabolite quantitative traits by exome
      sequence analyses.
AB  - Metabolite quantitative traits carry great promise for epidemiological studies,
      and their genetic background has been addressed using Genome-Wide Association
      Studies (GWAS). Thus far, the role of less common variants has not been
      exhaustively studied. Here, we set out a GWAS for metabolite quantitative traits
      in serum, followed by exome sequence analysis to zoom in on putative causal
      variants in the associated genes. 1H Nuclear Magnetic Resonance (1H-NMR)
      spectroscopy experiments yielded successful quantification of 42 unique
      metabolites in 2,482 individuals from The Erasmus Rucphen Family (ERF) study.
      Heritability of metabolites were estimated by SOLAR. GWAS was performed by linear
      mixed models, using HapMap imputations. Based on physical vicinity and pathway
      analyses, candidate genes were screened for coding region variation using exome
      sequence data. Heritability estimates for metabolites ranged between 10% and 52%.
      GWAS replicated three known loci in the metabolome wide significance: CPS1 with
      glycine (P-value  = 1.27*10-32), PRODH with proline (P-value  = 1.11*10-19),
      SLC16A9 with carnitine level (P-value  = 4.81*10-14) and uncovered a novel
      association between DMGDH and dimethyl-glycine (P-value  = 1.65*10-19) level. In
      addition, we found three novel, suggestively significant loci: TNP1 with pyruvate
      (P-value  = 1.26*10-8), KCNJ16 with 3-hydroxybutyrate (P-value  = 1.65*10-8) and
      2p12 locus with valine (P-value  = 3.49*10-8). Exome sequence analysis identified
      potentially causal coding and regulatory variants located in the genes CPS1,
      KCNJ2 and PRODH, and revealed allelic heterogeneity for CPS1 and PRODH. Combined
      GWAS and exome analyses of metabolites detected by high-resolution 1H-NMR is a
      robust approach to uncover metabolite quantitative trait loci (mQTL), and the
      likely causative variants in these loci. It is anticipated that insight in the
      genetics of intermediate phenotypes will provide additional insight into the
      genetics of complex traits. 

PMID- 25569238
TI  - Pilin Processing Follows a Different Temporal Route than That of Archaellins in
      Methanococcus maripaludis.
AB  - Methanococcus maripaludis has two different surface appendages: type IV-like pili
      and archaella. Both structures are believed to be assembled using a bacterial
      type IV pilus mechanism. Each structure is composed of multiple subunits, either
      pilins or archaellins. Both pilins and archaellins are made initially as
      preproteins with type IV pilin-like signal peptides, which must be removed by a
      prepilin peptidase-like enzyme. This enzyme is FlaK for archaellins and EppA for
      pilins. In addition, both pilins and archaellins are modified with N-linked
      glycans. The archaellins possess an N-linked tetrasaccharide while the pilins
      have a pentasaccharide which consists of the archaellin tetrasaccharide but with
      an additional sugar, an unidentified hexose, attached to the linking sugar. In
      this report, we show that archaellins can be processed by FlaK in the absence of
      N-glycosylation and N-glycosylation can occur on archaellins that still retain
      their signal peptides. In contrast, pilins are not glycosylated unless they have
      been acted on by EppA to have the signal peptide removed. However, EppA can still
      remove signal peptides from non-glycosylated pilins. These findings indicate that
      there is a difference in the order of the posttranslational modifications of
      pilins and archaellins even though both are type IV pilin-like proteins. 

PMID- 25569239
TI  - Sucrose in cyanobacteria: from a salt-response molecule to play a key role in
      nitrogen fixation.
AB  - In the biosphere, sucrose is mainly synthesized in oxygenic photosynthetic
      organisms, such as cyanobacteria, green algae and land plants, as part of the
      carbon dioxide assimilation pathway. Even though its central position in the
      functional biology of plants is well documented, much less is known about the
      role of sucrose in cyanobacteria. In those prokaryotes, sucrose accumulation has
      been associated with salt acclimation, and considered as a compatible solute in
      low-salt tolerant strains. In the last years, functional characterizations of
      sucrose metabolizing enzymes, metabolic control analysis, cellular localization
      of gene expressions, and reverse genetic experiments have revealed that sucrose
      metabolism is crucial in the diazotrophic growth of heterocystic strains, and
      besides, that it can be connected to glycogen synthesis. This article briefly
      summarizes the current state of knowledge of sucrose physiological functions in
      modern cyanobacteria and how they might have evolved taking into account the
      phylogenetic analyses of sucrose enzymes. 

PMID- 25569241
TI  - The complex association of metabolic syndrome and its components with computed
      tomography-determined emphysema index.
AB  - BACKGROUND: Recent reports have suggested the association between emphysema and
      cardiovascular disease (CVD); however, there are few reports regarding
      association of emphysema severity with metabolic syndrome and its components
      representing CVD risk factors. METHODS: A retrospective cross-sectional study was
      performed in 2814 adult male subjects over age 40 who visited the Health
      Promotion Center in Samsung Medical Center for a health checkup program. RESULTS:
      We classified patients according to the quintiles of forced expiratory volume in
      1 sec (FEV1) and emphysema index (EI). FEV1 percentage predicted values (% pred)
      was inversely associated with prevalence of metabolic syndrome and most of its
      components, such as abdominal obesity, hypertension, fasting hyperglycemia, and
      low high-density lipoprotein cholesterol. Although there was no association
      between prevalence of metabolic syndrome and EI, hypertension was positively
      associated with EI (P<0.001) and high triglycerides (TGs) were inversely
      associated with EI (P=0.021). These associations persisted after adjustment of
      other variables (P<0.001 in hypertension and P=0.039 in high TGs). CONCLUSION:
      The computed tomography-determined EI has a complex association with components
      of metabolic syndrome that is associated with increased prevalence of
      hypertension but decreased prevalence of high TGs, whereas FEV1 (% pred) has an
      inverse association with metabolic syndrome and most of its components with
      consistent direction.

PMID- 25569240
TI  - Identification of human semiochemicals attractive to the major vectors of
      onchocerciasis.
AB  - BACKGROUND: Entomological indicators are considered key metrics to document the
      interruption of transmission of Onchocerca volvulus, the etiological agent of
      human onchocerciasis. Human landing collection is the standard employed for
      collection of the vectors for this parasite. Recent studies reported the
      development of traps that have the potential for replacing humans for
      surveillance of O. volvulus in the vector population. However, the key chemical
      components of human odor that are attractive to vector black flies have not been
      identified. METHODOLOGY/PRINCIPAL FINDINGS: Human sweat compounds were analyzed
      using GC-MS analysis and compounds common to three individuals identified. These
      common compounds, with others previously identified as attractive to other
      hematophagous arthropods were evaluated for their ability to stimulate and
      attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato)
      and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y
      tube binary choice assay. Medium chain length carboxylic acids and aldehydes were
      neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by
      short chain aliphatic alcohols and aldehydes. Both species were attracted to
      ammonium bicarbonate and acetophenone. The compounds were shown to be attractive
      to the relevant vector species in field studies, when incorporated into a
      formulation that permitted a continuous release of the compound over time and
      used in concert with previously developed trap platforms.
      CONCLUSIONS/SIGNIFICANCE: The identification of compounds attractive to the major
      vectors of O. volvulus will permit the development of optimized traps. Such traps
      may replace the use of human vector collectors for monitoring the effectiveness
      of onchocerciasis elimination programs and could find use as a contributing
      component in an integrated vector control/drug program aimed at eliminating river
      blindness in Africa.

PMID- 25569243
TI  - Improving diabetes care: six simple suggestions.

PMID- 25569242
TI  - Adolescent outcomes of children with early speech sound disorders with and
      without language impairment.
AB  - PURPOSE: In this study, the authors determined adolescent speech, language, and
      literacy outcomes of individuals with histories of early childhood speech sound
      disorders (SSD) with and without comorbid language impairment (LI) and examined
      factors associated with these outcomes. METHOD: This study used a prospective
      longitudinal design. Participants with SSD (n = 170), enrolled at early childhood
      (4-6 years) were followed at adolescence (11-18 years) and were compared to
      individuals with no histories of speech or language impairment (no SSD; n = 146)
      on measures of speech, language, and literacy. Comparisons were made between
      adolescents with early childhood histories of no SSD, SSD only, and SSD plus LI
      as well as between adolescents with no SSD, resolved SSD, and persistent SSD.
      RESULTS: Individuals with early childhood SSD with comorbid LI had poorer
      outcomes than those with histories of SSD only or no SSD. Poorer language and
      literacy outcomes in adolescence were associated with multiple factors, including
      persistent speech sound problems, lower nonverbal intelligence, and lower
      socioeconomic status. Adolescents with persistent SSD had higher rates of
      comorbid LI and reading disability than the no SSD and resolved SSD groups.
      CONCLUSION: Risk factors for language and literacy problems in adolescence
      include an early history of LI, persistent SSD, lower nonverbal cognitive
      ability, and social disadvantage.

PMID- 25569244
TI  - A method for efficient expression of Pseudomonas aeruginosa alginate lyase in
      Pichia pastoris.
AB  - As an eco-friendly biocatalyst for alginate hydrolysis, bacteria-derived alginate
      lyase (AlgL) has been widely used in research and industries to produce
      oligosaccharides. However, the cost of AlgL enzyme production remains high due to
      the low expression and difficulty in purification from bacterial cells. In this
      study we report an effective method to overexpress the Pseudomonas aeruginosa
      AlgL (paAlgL) enzyme in Pichia pastoris. Fused with a secretory peptide, the
      recombinant paAlgL was expressed extracellularly and purified from the culture
      supernatant through a simple process. The purified recombinant enzyme is highly
      specific for alginate sodium with a maximal activity of 2,440 U/mg. The enzymatic
      activity remained stable below 45 degrees C and at pH between 4 and 10. The
      recombinant paAlgL was inhibited by Zn(2+), Cu(2+), and Fe(2+) and promoted by
      Co(2+) and Ca(2+). Interestingly, we also found that the recombinant paAlgL
      significantly enhanced the antimicrobial activity of antibiotics ampicillin and
      kanamycin against Pseudomonas aeruginosa. Our results introduce a method for
      efficient AlgL production, the characterization, and a new feature of the
      recombinant paAlgL as an enhancer of antibiotics against Pseudomonas aeruginosa.

PMID- 25569245
TI  - "By the way doctor, I've booked an African safari after my next chemo".

PMID- 25569247
TI  - US cancer mortality continues to fall.

PMID- 25569246
TI  - Gene therapy of c-myc suppressor FUSE-binding protein-interacting repressor by
      Sendai virus delivery prevents tracheal stenosis.
AB  - Acquired tracheal stenosis remains a challenging problem for otolaryngologists.
      The objective of this study was to determine whether the Sendai virus (SeV)
      mediated c-myc suppressor, a far upstream element (FUSE)-binding protein (FBP)
      interacting repressor (FIR), modulates wound healing of the airway mucosa, and
      whether it prevents tracheal stenosis in an animal model of induced mucosal
      injury. A fusion gene-deleted, non-transmissible SeV vector encoding FIR (FIR
      SeV/DeltaF) was prepared. Rats with scraped airway mucosae were administered FIR
      SeV/DeltaF through the tracheostoma. The pathological changes in the airway
      mucosa and in the tracheal lumen were assessed five days after scraping.
      Untreated animals showed hyperplasia of the airway epithelium and a thickened
      submucosal layer with extensive fibrosis, angiogenesis, and collagen deposition
      causing lumen stenosis. By contrast, the administration of FIR-SeV/DeltaF
      decreased the degree of tracheal stenosis (P < 0.05) and improved the survival
      rate (P < 0.05). Immunohistochemical staining showed that c-Myc expression was
      downregulated in the tracheal basal cells of the FIR-SeV/DeltaF-treated animals,
      suggesting that c-myc was suppressed by FIR-SeV/DeltaF in the regenerating airway
      epithelium of the injured tracheal mucosa. The airway-targeted gene therapy of
      the c-myc suppressor FIR, using a recombinant SeV vector, prevented tracheal
      stenosis in a rat model of airway mucosal injury. 

PMID- 25569248
TI  - Burden of disease measured by disability-adjusted life years and a disease
      forecasting time series model of scrub typhus in Laiwu, China.
AB  - BACKGROUND: Laiwu District is recognized as a hyper-endemic region for scrub
      typhus in Shandong Province, but the seriousness of this problem has been
      neglected in public health circles. METHODOLOGY/PRINCIPAL FINDINGS: A disability
      adjusted life years (DALYs) approach was adopted to measure the burden of scrub
      typhus in Laiwu, China during the period 2006 to 2012. A multiple seasonal
      autoregressive integrated moving average model (SARIMA) was used to identify the
      most suitable forecasting model for scrub typhus in Laiwu. Results showed that
      the disease burden of scrub typhus is increasing yearly in Laiwu, and which is
      higher in females than males. For both females and males, DALY rates were highest
      for the 60-69 age group. Of all the SARIMA models tested, the
      SARIMA(2,1,0)(0,1,0)12 model was the best fit for scrub typhus cases in Laiwu.
      Human infections occurred mainly in autumn with peaks in October.
      CONCLUSIONS/SIGNIFICANCE: Females, especially those of 60 to 69 years of age,
      were at highest risk of developing scrub typhus in Laiwu, China. The SARIMA
      (2,1,0)(0,1,0)12 model was the best fit forecasting model for scrub typhus in
      Laiwu, China. These data are useful for developing public health education and
      intervention programs to reduce disease.

PMID- 25569249
TI  - Should doctors encourage patients to record consultations?

PMID- 25569251
TI  - What have we learned from 40 years of supporting research and capacity building?

PMID- 25569250
TI  - Parasite biomass-related inflammation, endothelial activation, microvascular
      dysfunction and disease severity in vivax malaria.
AB  - Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly
      understood. In contrast to P. falciparum, circulating vivax parasitemia is low,
      with minimal apparent sequestration in endothelium-lined microvasculature, and
      pathogenesis thought unrelated to parasite biomass. However, the relationships
      between vivax disease-severity and total parasite biomass, endothelial autocrine
      activation and microvascular dysfunction are unknown. We measured circulating
      parasitemia and markers of total parasite biomass (plasma parasite lactate
      dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n =
      53) vivax malaria, and examined relationships with disease-severity, endothelial
      activation, and microvascular function. Healthy controls and adults with non
      severe and severe falciparum malaria were enrolled for comparison. Median
      peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold
      higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p =
      0.015, respectively), suggesting that, as in falciparum malaria, peripheral P.
      vivax parasitemia underestimates total parasite biomass, particularly in severe
      disease. P. vivax schizonts were under-represented in peripheral blood. Severe
      vivax malaria was associated with increased angiopoietin-2 and impaired
      microvascular reactivity. Peripheral vivax parasitemia correlated with
      endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin),
      whereas markers of total vivax biomass correlated only with systemic inflammation
      (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in
      proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease
      severity, and associated with impaired microvascular reactivity in severe
      disease. Impaired microvascular reactivity correlated with lactate in severe
      vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur,
      with the hidden biomass greatest in severe disease and capable of mediating
      systemic inflammatory pathology. The lack of association between total parasite
      biomass and endothelial activation is consistent with accumulation in parts of
      the circulation devoid of endothelium. Endothelial activation, associated with
      circulating parasites, and systemic inflammation may contribute to pathology in
      vivax malaria, with microvascular dysfunction likely contributing to impaired
      tissue perfusion. 

PMID- 25569252
TI  - Cost-effectiveness of antivenoms for snakebite envenoming in Nigeria.
AB  - BACKGROUND: Snakebite envenoming is a major public health problem throughout the
      rural tropics. Antivenom is effective in reducing mortality and remains the
      mainstay of therapy. This study aimed to determine the cost-effectiveness of
      using effective antivenoms for Snakebite envenoming in Nigeria. METHODOLOGY:
      Economic analysis was conducted from a public healthcare system perspective.
      Estimates of model inputs were obtained from the literature. Incremental Cost
      Effectiveness Ratios (ICERs) were quantified as deaths and Disability-Adjusted
      Life-Years (DALY) averted from antivenom therapy. A decision analytic model was
      developed and analyzed with the following model base-case parameter estimates:
      type of snakes causing bites, antivenom effectiveness to prevent death, untreated
      mortality, risk of Early Adverse Reactions (EAR), mortality risk from EAR, mean
      age at bite and remaining life expectancy, and disability risk (amputation). End
      user costs applied included: costs of diagnosing and monitoring envenoming,
      antivenom drug cost, supportive care, shipping/freezing antivenom, transportation
      to-and-from hospital and feeding costs while on admission, management of
      antivenom EAR and free alternative snakebite care for ineffective antivenom.
      PRINCIPAL FINDINGS: We calculated a cost/death averted of ($2330.16) and
      cost/DALY averted of $99.61 discounted and $56.88 undiscounted. Varying antivenom
      effectiveness through the 95% confidence interval from 55% to 86% yield a
      cost/DALY averted of $137.02 to $86.61 respectively. Similarly, varying the
      prevalence of envenoming caused by carpet viper from 0% to 96% yield a cost/DALY
      averted of $254.18 to $78.25 respectively. More effective antivenoms and carpet
      viper envenoming rather than non-carpet viper envenoming were associated with
      lower cost/DALY averted. CONCLUSIONS/SIGNIFICANCE: Treatment of snakebite
      envenoming in Nigeria is cost-effective with a cost/death averted of $2330.16 and
      cost/DALY averted of $99.61 discounted, lower than the country's gross domestic
      product per capita of $1555 (2013). Expanding access to effective antivenoms to
      larger segments of the Nigerian population should be a considered a priority.

PMID- 25569253
TI  - Sumoylation influences DNA break repair partly by increasing the solubility of a
      conserved end resection protein.
AB  - Protein modifications regulate both DNA repair levels and pathway choice. How
      each modification achieves regulatory effects and how different modifications
      collaborate with each other are important questions to be answered. Here, we show
      that sumoylation regulates double-strand break repair partly by modifying the end
      resection factor Sae2. This modification is conserved from yeast to humans, and
      is induced by DNA damage. We mapped the sumoylation site of Sae2 to a single
      lysine in its self-association domain. Abolishing Sae2 sumoylation by mutating
      this lysine to arginine impaired Sae2 function in the processing and repair of
      multiple types of DNA breaks. We found that Sae2 sumoylation occurs independently
      of its phosphorylation, and the two modifications act in synergy to increase
      soluble forms of Sae2. We also provide evidence that sumoylation of the Sae2
      binding nuclease, the Mre11-Rad50-Xrs2 complex, further increases end resection.
      These findings reveal a novel role for sumoylation in DNA repair by regulating
      the solubility of an end resection factor. They also show that collaboration
      between different modifications and among multiple substrates leads to a stronger
      biological effect. 

PMID- 25569254
TI  - ASAR15, A cis-acting locus that controls chromosome-wide replication timing and
      stability of human chromosome 15.
AB  - DNA replication initiates at multiple sites along each mammalian chromosome at
      different times during each S phase, following a temporal replication program. We
      have used a Cre/loxP-based strategy to identify cis-acting elements that control
      this replication-timing program on individual human chromosomes. In this report,
      we show that rearrangements at a complex locus at chromosome 15q24.3 result in
      delayed replication and structural instability of human chromosome 15.
      Characterization of this locus identified long, RNA transcripts that are retained
      in the nucleus and form a "cloud" on one homolog of chromosome 15. We also found
      that this locus displays asynchronous replication that is coordinated with other
      random monoallelic genes on chromosome 15. We have named this locus ASynchronous
      replication and Autosomal RNA on chromosome 15, or ASAR15. Previously, we found
      that disruption of the ASAR6 lincRNA gene results in delayed replication, delayed
      mitotic condensation and structural instability of human chromosome 6. Previous
      studies in the mouse found that deletion of the Xist gene, from the X chromosome
      in adult somatic cells, results in a delayed replication and instability
      phenotype that is indistinguishable from the phenotype caused by disruption of
      either ASAR6 or ASAR15. In addition, delayed replication and chromosome
      instability were detected following structural rearrangement of many different
      human or mouse chromosomes. These observations suggest that all mammalian
      chromosomes contain similar cis-acting loci. Thus, under this scenario, all
      mammalian chromosomes contain four distinct types of essential cis-acting
      elements: origins, telomeres, centromeres and "inactivation/stability centers",
      all functioning to promote proper replication, segregation and structural
      stability of each chromosome. 

PMID- 25569255
TI  - The genetic and mechanistic basis for variation in gene regulation.
AB  - It is now well established that noncoding regulatory variants play a central role
      in the genetics of common diseases and in evolution. However, until recently, we
      have known little about the mechanisms by which most regulatory variants act. For
      instance, what types of functional elements in DNA, RNA, or proteins are most
      often affected by regulatory variants? Which stages of gene regulation are
      typically altered? How can we predict which variants are most likely to impact
      regulation in a given cell type? Recent studies, in many cases using quantitative
      trait loci (QTL)-mapping approaches in cell lines or tissue samples, have
      provided us with considerable insight into the properties of genetic loci that
      have regulatory roles. Such studies have uncovered novel biochemical regulatory
      interactions and led to the identification of previously unrecognized regulatory
      mechanisms. We have learned that genetic variation is often directly associated
      with variation in regulatory activities (namely, we can map regulatory QTLs, not
      just expression QTLs [eQTLs]), and we have taken the first steps towards
      understanding the causal order of regulatory events (for example, the role of
      pioneer transcription factors). Yet, in most cases, we still do not know how to
      interpret overlapping combinations of regulatory interactions, and we are still
      far from being able to predict how variation in regulatory mechanisms is
      propagated through a chain of interactions to eventually result in changes in
      gene expression profiles. 

PMID- 25569257
TI  - 150 years of the mass action law.
AB  - This year we celebrate the 150th anniversary of the law of mass action. This law
      is often assumed to have been "there" forever, but it has its own history,
      background, and a definite starting point. The law has had an impact on
      chemistry, biochemistry, biomathematics, and systems biology that is difficult to
      overestimate. It is easily recognized that it is the direct basis for
      computational enzyme kinetics, ecological systems models, and models for the
      spread of diseases. The article reviews the explicit and implicit role of the law
      of mass action in systems biology and reveals how the original, more general
      formulation of the law emerged one hundred years later ab initio as a very
      general, canonical representation of biological processes. 

PMID- 25569256
TI  - Elevated mutation rate during meiosis in Saccharomyces cerevisiae.
AB  - Mutations accumulate during all stages of growth, but only germ line mutations
      contribute to evolution. While meiosis contributes to evolution by reassortment
      of parental alleles, we show here that the process itself is inherently
      mutagenic. We have previously shown that the DNA synthesis associated with repair
      of a double-strand break is about 1000-fold less accurate than S-phase synthesis.
      Since the process of meiosis involves many programmed DSBs, we reasoned that this
      repair might also be mutagenic. Indeed, in the early 1960's Magni and Von Borstel
      observed elevated reversion of recessive alleles during meiosis, and found that
      the revertants were more likely to be associated with a crossover than non
      revertants, a process that they called "the meiotic effect." Here we use a
      forward mutation reporter (CAN1 HIS3) placed at either a meiotic recombination
      coldspot or hotspot near the MAT locus on Chromosome III. We find that the
      increased mutation rate at CAN1 (6 to 21 -fold) correlates with the underlying
      recombination rate at the locus. Importantly, we show that the elevated mutation
      rate is fully dependent upon Spo11, the protein that introduces the meiosis
      specific DSBs. To examine associated recombination we selected for random spores
      with or without a mutation in CAN1. We find that the mutations isolated this way
      show an increased association with recombination (crossovers, loss of crossover
      interference and/or increased gene conversion tracts). Polzeta appears to
      contribute about half of the mutations induced during meiosis, but is not the
      only source of mutations for the meiotic effect. We see no difference in either
      the spectrum or distribution of mutations between mitosis and meiosis. The
      correlation of hotspots with elevated mutagenesis provides a mechanism for
      organisms to control evolution rates in a gene specific manner. 

PMID- 25569259
TI  - Paul McMaster: At times a real pain.

PMID- 25569258
TI  - In silico repositioning-chemogenomics strategy identifies new drugs with
      potential activity against multiple life stages of Schistosoma mansoni.
AB  - Morbidity and mortality caused by schistosomiasis are serious public health
      problems in developing countries. Because praziquantel is the only drug in
      therapeutic use, the risk of drug resistance is a concern. In the search for new
      schistosomicidal drugs, we performed a target-based chemogenomics screen of a
      dataset of 2,114 proteins to identify drugs that are approved for clinical use in
      humans that may be active against multiple life stages of Schistosoma mansoni.
      Each of these proteins was treated as a potential drug target, and its amino acid
      sequence was used to interrogate three databases: Therapeutic Target Database
      (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using
      a combination of approaches, including pairwise alignment, conservation state of
      functional regions and chemical space analysis. To validate our strategy, several
      drugs previously shown to be active against Schistosoma species were correctly
      predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were
      also able to identify 115 drugs that have not yet been experimentally tested
      against schistosomes and that require further assessment. Some examples are
      aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and
      cinnarizine. In conclusion, we have developed a systematic and focused computer
      aided approach to propose approved drugs that may warrant testing and/or serve as
      lead compounds for the design of new drugs against schistosomes. 

PMID- 25569260
TI  - A mutation in caspase-9 decreases the expression of BAFFR and ICOS in patients
      with immunodeficiency and lymphoproliferation.
AB  - Lymphocyte apoptosis is mainly induced by either death receptor-dependent
      activation of caspase-8 or mitochondria-dependent activation of caspase-9.
      Mutations in caspase-8 lead to autoimmunity/lymphoproliferation and
      immunodeficiency. This work describes a heterozygous H237P mutation in caspase-9
      that can lead to similar disorders. H237P mutation was detected in two patients:
      Pt1 with autoimmunity/lymphoproliferation, severe hypogammaglobulinemia and Pt2
      with mild hypogammaglobulinemia and Burkitt lymphoma. Their lymphocytes displayed
      defective caspase-9 activity and decreased apoptotic and activation responses.
      Transfection experiments showed that mutant caspase-9 display defective enzyme
      and proapoptotic activities and a dominant-negative effect on wild-type caspase
      9. Ex vivo analysis of the patients' lymphocytes and in vitro transfection
      experiments showed that the expression of mutant caspase-9 correlated with a
      downregulation of BAFFR (B-cell-activating factor belonging to the TNF family
      (BAFF) receptor) in B cells and ICOS (inducible T-cell costimulator) in T cells.
      Both patients carried a second inherited heterozygous mutation missing in the
      relatives carrying H237P: Pt1 in the transmembrane activator and CAML interactor
      (TACI) gene (S144X) and Pt2 in the perforin (PRF1) gene (N252S). Both mutations
      have been previously associated with immunodeficiencies in homozygosis or
      compound heterozygosis. Taken together, these data suggest that caspase-9
      mutations may predispose to immunodeficiency by cooperating with other genetic
      factors, possibly by downregulating the expression of BAFFR and ICOS. 

PMID- 25569261
TI  - The genetic basis for susceptibility to Rift Valley fever disease in MBT/Pas
      mice.
AB  - The large variation in individual response to infection with Rift Valley fever
      virus (RVFV) suggests that host genetic determinants play a role in determining
      virus-induced disease outcomes. These genetic factors are still unknown. The
      systemic inoculation of mice with RVFV reproduces major pathological features of
      severe human disease, notably the hepatitis and encephalitis. A genome scan
      performed on 546 (BALB/c * MBT) F2 progeny identified three quantitative trait
      loci (QTLs), denoted Rvfs-1 to Rvfs-3, that were associated with disease
      susceptibility in MBT/Pas mice. Non-parametric interval-mapping revealed one
      significant and two suggestive linkages with survival time on chromosomes 2 (Rvfs
      1), 5 (Rvfs-3) and 11 (Rvfs-2) with respective logarithm of odds (LOD) scores of
      4.58, 2.95 and 2.99. The two-part model, combining survival time and
      survival/death, identified one significant linkage to Rvfs-2 and one suggestive
      linkage to Rvfs-1 with respective LOD scores of 5.12 and 4.55. Under a multiple
      model, with additive effects and sex as a covariate, the three QTLs explained
      8.3% of the phenotypic variance. Sex had the strongest influence on
      susceptibility. The contribution of Rvfs-1, Rvfs-2 and Rvfs-3 to survival time of
      RVFV-infected mice was further confirmed in congenic mice. 

PMID- 25569262
TI  - Association of complement receptor 2 polymorphisms with innate resistance to HIV
      1 infection.
AB  - HIV-1 induces activation of complement through the classical and lectin pathways.
      However, the virus incorporates several membrane-bound or soluble regulators of
      complement activation (RCA) that inactivate complement. HIV-1 can also use the
      complement receptors (CRs) for complement-mediated antibody-dependent enhancement
      of infection (C-ADE). We hypothesize that hypofunctional polymorphisms in RCA or
      CRs may protect from HIV-1 infection. For this purpose, 139 SNPs located in 19
      RCA and CRs genes were genotyped in a population of 201 Spanish HIV-1-exposed
      seronegative individuals (HESN) and 250 HIV-1-infected patients. Two SNPs were
      associated with infection susceptibility, rs1567190 in CR2 (odds ratio (OR) =
      2.27, P = 1 * 10(-4)) and rs2842704 in C4BPA (OR = 2.11, P = 2 * 10(-4)). To
      replicate this finding, we analyzed a cohort of Italian, sexually HESN
      individuals. Although not significant (P = 0.25, OR = 1.57), similar genotypic
      proportions were obtained for the CR2 marker rs1567190. The results of the two
      association analyses were combined through a random effect meta-analysis, with a
      significant P-value of 2.6 x 10(-5) (OR = 2.07). Furthermore, we found that the
      protective CR2 genotype is correlated with lower levels CR2 mRNA as well as
      differences in the ratio of the long and short CR2 isoforms.

PMID- 25569264
TI  - KMT1E-mediated chromatin modifications at the FcgammaRIIb promoter regulate
      thymocyte development.
AB  - This work examines the role the lysine methyltransferase KMT1E (Setdb1) in
      thymocyte development. We have developed and described a T cell-specific
      conditional knockout of Setdb1. A partial block was seen at the double-positive
      to single-positive transition, causing reduced numbers of single-positive T cells
      in the thymus and periphery. Knockout thymocytes had reduced numbers of CD69(+)
      and T-cell receptor TCRbeta(+) cells and increased numbers of apoptotic cells in
      the double-positive compartment, suggesting an alteration in the selection
      process. Transcriptional profiling of thymocytes revealed that Setdb1 deletion
      derepresses expression of FcgammaRIIb, the inhibitory Fc receptor. We demonstrate
      that a KMT1E-containing complex directly interacts with the FcgammaRIIb promoter
      and that histone H3 at lysine 9 tri-methylation at this promoter is dependent on
      Setdb1 expression. Derepression of FcgammaRIIb causes exacerbated signaling
      through the TCR complex, with specifically increased phosphorylation of ZAP70,
      affecting selection. This work identifies KMT1E as a novel repressor of
      FcgammaRIIb and identifies an underappreciated role of FcgammaRIIb in fine tuning
      thymocyte development. 

PMID- 25569263
TI  - The cumulative effects of known susceptibility variants to predict primary
      biliary cirrhosis risk.
AB  - Multiple genetic variants influence the risk for development of primary biliary
      cirrhosis (PBC). To explore the cumulative effects of known susceptibility loci
      on risk, we utilized a weighted genetic risk score (wGRS) to evaluate whether
      genetic information can predict susceptibility. The wGRS was created using 26
      known susceptibility loci and investigated in 1840 UK PBC and 5164 controls. Our
      data indicate that the wGRS was significantly different between PBC and controls
      (P=1.61E-142). Moreover, we assessed predictive performance of wGRS on disease
      status by calculating the area under the receiver operator characteristic curve.
      The area under curve for the purely genetic model was 0.72 and for gender plus
      genetic model was 0.82, with confidence limits substantially above random
      predictions. The risk of PBC using logistic regression was estimated after
      dividing individuals into quartiles. Individuals in the highest disclosed risk
      group demonstrated a substantially increased risk for PBC compared with the
      lowest risk group (odds ratio: 9.3, P=1.91E-084). Finally, we validated our
      findings in an analysis of an Italian PBC cohort. Our data suggested that the
      wGRS, utilizing genetic variants, was significantly associated with increased
      risk for PBC with consistent discriminant ability. Our study is a first step
      toward risk prediction for PBC. 

PMID- 25569265
TI  - The higher frequency of IgA deficiency among Swedish twins is not explained by
      HLA haplotypes.
AB  - Serum immunoglobulin A (IgA) concentrations were determined in 12 600 adult
      Swedish twins, applying a high-throughput reverse-phase protein microarray
      technique. The prevalence of IgA deficiency (IgAD) was found to be 1:241 in
      monozygotic (MZ) twins and 1:198 in dizygotic (DZ) twins. Hence, the prevalence
      in twins is markedly elevated as compared with the normal Swedish adult
      population (1:600). The twins did not show a difference in the frequency of HLA
      haplotypes in comparison with almost 40 000 healthy Swedish controls. As
      expected, the risk-conveying HLA alleles A*01, B*08 and DRB1*01 were
      overrepresented among the IgAD twins and were also associated with significantly
      lower mean serum IgA concentrations in the twin cohort. In contrast,
      significantly higher mean IgA concentrations were found among individuals
      carrying the protective HLA alleles B*07 and DRB1*15. Exome sequencing data from
      two MZ twin pairs discordant for the deficiency showed no differences between the
      siblings. Model fitting analyses derived a heritability of 35% and indicate that
      genetic influences are modestly important for IgAD. The probandwise concordance
      rates for IgAD were found to be 31% for MZ and 13% for DZ twins. 

PMID- 25569267
TI  - A rare case of mixed gonadal dysgenesis with mosaicism 45, X/46, X, +mar.
AB  - INTRODUCTION: We present a rare patient case with mixed gonadal dysgenesis as a
      disorder of sex development (DSD) and a new pattern of chromosome in the
      karyotype, 45, X/46, X, +mar(Y). PRESENTATION OF CASE: A ten-year-old boy, raised
      in a nursery center, presented with ambiguous genitalia. Two cell lines, (45, X)
      and [46,X, +mar(Y)] were observed utilizing cytogenetic investigation including
      fluorescence in situ hybridization (FISH) which were carried out on his
      peripheral lymphocytes. A significantly higher percentage (75%) of Y-containing
      cells was observed in the blood, which could be considered the major reason why
      the case did not have distinct ambiguous genitalia. A further explorative
      laparoscopic procedure was performed, during which orchiectomy was performed, and
      remnants of Mullerian duct were excised. DISCUSSION: A complete and sufficiently
      careful medical evaluation and genetics counseling of neonates is highly
      recommended in order to avoid any delayed insufficient diagnostic, conservative,
      and therapeutic care in children living with guardians rather than their
      biological parents. Both molecular and cytogenetic studies are recommended in
      some DSDs to help early diagnosis of the disease, which is important for further
      essential surgical approaches. CONCLUSION: Cytogenetic studies followed by a
      laparoscopic exploratory and surgical survey are helpful tools for unraveling the
      mosaicism involving sex chromosomes and the complicated process in mixed gonadal
      dysgenesis patients.

PMID- 25569269
TI  - Analysis of residual thrombotic burden after thrombus aspiration in acute ST
      elevation myocardial infarction: An optical coherence tomographic evaluation.

PMID- 25569266
TI  - Genetic association of CD247 (CD3zeta) with SLE in a large-scale multiethnic
      study.
AB  - A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the
      downregulation and replacement of the CD3zeta chain that alters T-cell receptor
      signaling. However, genetic associations with SLE in the human CD247 locus that
      encodes CD3zeta are not well established and require replication in independent
      cohorts. Our aim was therefore to examine, localize and validate CD247-SLE
      association in a large multiethnic population. We typed 44 contiguous CD247
      single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls
      from four ethnically distinct populations. The strongest associations were found
      in the Asian population (11 SNPs in intron 1, 4.99 * 10(-4) < P < 4.15 * 10(-2)),
      where we further identified a five-marker haplotype (rs12141731-rs2949655
      rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 * 10(-5)) that exceeded
      the most associated single SNP rs858554 (minor allele frequency in controls =
      13%; P = 4.99 * 10(-4), odds ratio = 1.32) in significance. Imputation and
      subsequent association analysis showed evidence of association (P < 0.05) at 27
      additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive
      genetic model adjusted for population proportions, showed five SNPs with
      significant P-values (1.40 * 10(-3) < P< 3.97 * 10(-2)), with one (rs704848)
      remaining significant after Bonferroni correction (P(meta) = 2.66 * 10(-2)). Our
      study independently confirms and extends the association of SLE with CD247, which
      is shared by various autoimmune disorders and supports a common T-cell-mediated
      mechanism.

PMID- 25569270
TI  - Cost-effectiveness analysis of alternative screening and treatment strategies for
      heterozygous familial hypercholesterolemia in the United States.
AB  - BACKGROUND/OBJECTIVES: Familial hypercholesterolemia (FH) is a genetic disorder
      that leads to premature heart disease or stroke if untreated. Statins are
      effective for individuals with FH but less than 20% of actual cases are diagnosed
      in the US and many people are not adherent to treatment. Using new knowledge
      regarding mutations responsible for FH, some European countries have developed
      genetic FH screening strategies, many of which have been shown to be cost
      effective. This study evaluates the cost-effectiveness of genetic screening and
      lipid-based screening with statin adherence measures compared to lipid-based
      screening alone in the US. METHODS: A decision tree was used to estimate disease
      detection with the three screening strategies, while a Markov model was used to
      model disease progression until death, quality-adjusted life years (QALYs) and
      costs from a US societal perspective. RESULTS: The results showed that Genetic
      Screening cost $15,594 for 18.29 QALYs per person and Lipid Screening with
      adherence measures cost $16,385 for 18.77 QALYs compared with $10,396 for 18.28
      QALYs for Lipid Screening alone. The incremental cost-effectiveness ratio (ICER)
      of Genetic Screening versus Lipid Screening was $519,813/QALY and that of Lipid
      Screening with adherence measures versus Lipid Screening alone was $12,223/QALY.
      At a US willingness-to-pay threshold of $150,000/QALY Genetic Screening is not
      cost-effective compared with Lipid Screening. Sensitivity analyses showed that
      results were robust to reasonable variations in model parameters. CONCLUSIONS:
      Although genetic screening is currently not a cost-effective option in the US,
      health outcomes for FH individuals could benefit from adherence measures
      encouraging statin use.

PMID- 25569268
TI  - Flow damping due to stochastization of the magnetic field.
AB  - The driving and damping mechanism of plasma flow is an important issue because
      flow shear has a significant impact on turbulence in a plasma, which determines
      the transport in the magnetized plasma. Here we report clear evidence of the flow
      damping due to stochastization of the magnetic field. Abrupt damping of the
      toroidal flow associated with a transition from a nested magnetic flux surface to
      a stochastic magnetic field is observed when the magnetic shear at the rational
      surface decreases to 0.5 in the large helical device. This flow damping and
      resulting profile flattening are much stronger than expected from the Rechester
      Rosenbluth model. The toroidal flow shear shows a linear decay, while the ion
      temperature gradient shows an exponential decay. This observation suggests that
      the flow damping is due to the change in the non-diffusive term of momentum
      transport. 

PMID- 25569271
TI  - Impact of renin-angiotensin system inhibitors on mortality and major
      cardiovascular endpoints in hypertension: A number-needed-to-treat analysis.
AB  - OBJECTIVE: To assess the effectiveness of renin-angiotensin aldosterone system
      (RAAS) inhibitors to prevent all-cause and cardiovascular death, myocardial
      infarction and stroke in hypertensive patients considering the number needed to
      treat (NNT). METHODS: Data from a meta-analysis of 18 prospective, randomized,
      controlled morbidity-mortality trials (68 343 RAAS inhibitor; 84 543 control)
      were used to calculate NNTs for the prevention of all-cause and cardiovascular
      mortality, myocardial infarction, and stroke. RESULTS: Angiotensin-converting
      enzyme (ACE) inhibitors were used in 7 trials and angiotensin receptor blockers
      (ARBs) in 11 trials. Mean follow-up was 4.3years. The annual incidence rate of
      all-cause mortality was 0.0233 in patients randomized to RAAS inhibitors versus
      0.0252 in controls (hazard ratio 0.95, 95% confidence interval 0.91 to 0.99). The
      corresponding median NNT to prevent one death was 113 (2.5-97.5th percentile, 85
      to 168) in favor of RAAS inhibitors, which was driven by ACE inhibitors (NNT 67,
      2.5-97.5th percentile, 53 to 92) rather than ARBs (NNT 335, 2.5-97.5th
      percentile, -4341 to 5076). Results for cardiovascular mortality (NNT 116 for ACE
      inhibitors and 409 for ARBs, respectively) and myocardial infarction (NNT 80 and
      338, respectively) also appeared to be driven by ACE inhibitors. We found a lower
      NNT for stroke in favor of ARB (NNT 337 and 131, respectively) although this
      difference was statistically non-significant. CONCLUSION: Among hypertensive
      patients, ACE inhibitors but not ARBs, substantially reduce all-cause and
      cardiovascular mortality and myocardial infarction.

PMID- 25569273
TI  - Mature Driver Laws and State Predictors of Motor Vehicle Crash Fatality Rates
      Among the Elderly: A Cross-sectional Ecological Study.
AB  - OBJECTIVE: State-level data have indicated that motor vehicle crash (MVC)
      fatality rates among the elderly vary widely across states. To date, the majority
      of states have implemented mature driver laws, which often require more frequent
      license renewals, in-person renewal, and vision testing for drivers above a
      certain age. We sought to evaluate the impact of mature driver laws on states'
      MVC fatality rates among the elderly while examining other state-level
      determinants of MVC-related deaths. METHODS: We performed a cross-sectional
      ecological study and modeled state MVC fatality rates for the population over age
      65 as a function of state transportation policies and demographic, health system,
      population health, travel, and climate characteristics using a general linear
      model. Principal component analysis was used to reduce dimensionality of the data
      and overcome multicollinearity of state predictor variables. RESULTS: Higher
      average temperature, higher gas prices, and a greater number of emergency
      medicine physicians to population size were significantly associated with lower
      MVC fatality rates. Positive predictors of MVC fatality rates were percentage of
      population overweight or obese and percentage with college degree over the age of
      65. Having any restriction on elderly drivers was associated with a higher MVC
      fatality rate and no individual component of mature driver laws (shortened
      renewal cycle, in-person renewal, and vision testing) was significantly
      associated with lower fatality MVC rates for adults over 65. CONCLUSIONS: Mature
      driver laws are not associated with lower state MVC fatality rates among the
      elderly.

PMID- 25569272
TI  - Improving the diagnosis of LV non-compaction with cardiac magnetic resonance
      imaging.
AB  - BACKGROUND: Current diagnostic criteria for left ventricular non-compaction
      (LVNC) poorly correlate with clinical outcomes. We aimed to develop a cardiac
      magnetic resonance (CMR) based semi-automated technique for quantification of non
      compacted (NC) and compacted (C) masses and to ascertain their relationships to
      global and regional LV function. METHODS: We analysed CMR data from 30 adults
      with isolated LVNC and 20 controls. NC and C masses were measured using relative
      signal intensities of myocardium and blood pool. Global and regional LVNC masses
      was calculated and correlated with both global and regional LV systolic function
      as well as occurrence of arrhythmia. RESULTS: LVNC patients had significantly
      higher end-systolic (ES) and end-diastolic (ED) NC:C ratios compared to controls
      (ES 0.21 [SD 0.09] vs. 0.12 [SD 0.02], p<0.001; ED 0.39 [SD 0.08] vs. 0.26 [SD
      0.05], p<0.001). NC:C ratios correlated inversely with global ejection fraction,
      with a stronger correlation in ES vs. ED (r=-0.58, p<0.001 vs. r=-0.30, p=0.03).
      ES basal, mid and apical NC:C ratios also showed a significant inverse
      correlation with global LV ejection fraction (ES basal r=-0.29, p=0.04; mid
      ventricular r=-0.50, p<0.001 and apical r=-0.71, p<0.001). Upon ROC testing, an
      ES NC:C ratio of 0.16 had a sensitivity of 70% and a specificity of 95% for
      detection of significant LVNC. Patients with sustained ventricular tachycardia
      had a significantly higher ES NC:C ratio (0.31 [SD 0.18] vs. 0.20 [SD 0.06],
      p=0.02). CONCLUSIONS: The NC:C ratio derived from relative signal intensities of
      myocardium and blood pool improves the ability to detect clinically relevant NC
      compared to previous CMR techniques.

PMID- 25569274
TI  - Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12
      supplemented yogurt in healthy adults on antibiotics: a phase I safety study.
AB  - Probiotics are live microorganisms that, when administered in sufficient doses,
      provide health benefits on the host. The United States Food and Drug
      Administration (FDA) requires phase I safety studies for probiotics when the
      intended use of the product is as a drug. The purpose of the study was to
      determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain
      BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of
      adults who were prescribed a 10-day course of antibiotics for a respiratory
      infection. Secondary aims were to assess the ability of BB-12 to affect the
      expression of whole blood immune markers associated with cell activation and
      inflammatory response. A phase I, double-blinded, randomized controlled study was
      conducted in compliance with FDA guidelines for an Investigational New Drug
      (IND). Forty participants were randomly assigned to consume 4 ounces of either BB
      12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The
      primary outcome was to assess safety and tolerability, assessed by the number of
      reported adverse events. A total of 165 non-serious adverse events were reported,
      with no differences between the control and BB-12 groups. When compared to the
      control group, B lactis fecal levels were modestly higher in the BB-12
      supplemented group. In a small subset of patients, changes in whole blood
      expression of genes associated with regulation and activation of immune cells
      were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe
      and well tolerated when consumed by healthy adults concurrently taking
      antibiotics. This study will form the basis for future randomized clinical trials
      investigating the potential immunomodulatory effects of BB-12-supplemented yogurt
      in a variety of disease states. 

PMID- 25569275
TI  - Environmental drivers of the spatiotemporal dynamics of respiratory syncytial
      virus in the United States.
AB  - Epidemics of respiratory syncytial virus (RSV) are known to occur in wintertime
      in temperate countries including the United States, but there is a limited
      understanding of the importance of climatic drivers in determining the
      seasonality of RSV. In the United States, RSV activity is highly spatially
      structured, with seasonal peaks beginning in Florida in November through December
      and ending in the upper Midwest in February-March, and prolonged disease activity
      in the southeastern US. Using data on both age-specific hospitalizations and
      laboratory reports of RSV in the US, and employing a combination of statistical
      and mechanistic epidemic modeling, we examined the association between
      environmental variables and state-specific measures of RSV seasonality.
      Temperature, vapor pressure, precipitation, and potential evapotranspiration
      (PET) were significantly associated with the timing of RSV activity across states
      in univariate exploratory analyses. The amplitude and timing of seasonality in
      the transmission rate was significantly correlated with seasonal fluctuations in
      PET, and negatively correlated with mean vapor pressure, minimum temperature, and
      precipitation. States with low mean vapor pressure and the largest seasonal
      variation in PET tended to experience biennial patterns of RSV activity, with
      alternating years of "early-big" and "late-small" epidemics. Our model for the
      transmission dynamics of RSV was able to replicate these biennial transitions at
      higher amplitudes of seasonality in the transmission rate. This successfully
      connects environmental drivers to the epidemic dynamics of RSV; however, it does
      not fully explain why RSV activity begins in Florida, one of the warmest states,
      when RSV is a winter-seasonal pathogen. Understanding and predicting the
      seasonality of RSV is essential in determining the optimal timing of
      immunoprophylaxis. 

PMID- 25569276
TI  - Protein interactome of muscle invasive bladder cancer.
AB  - Muscle invasive bladder carcinoma is a complex, multifactorial disease caused by
      disruptions and alterations of several molecular pathways that result in
      heterogeneous phenotypes and variable disease outcome. Combining this disparate
      knowledge may offer insights for deciphering relevant molecular processes
      regarding targeted therapeutic approaches guided by molecular signatures allowing
      improved phenotype profiling. The aim of the study is to characterize muscle
      invasive bladder carcinoma on a molecular level by incorporating scientific
      literature screening and signatures from omics profiling. Public domain omics
      signatures together with molecular features associated with muscle invasive
      bladder cancer were derived from literature mining to provide 286 unique protein
      coding genes. These were integrated in a protein-interaction network to obtain a
      molecular functional map of the phenotype. This feature map educated on three
      novel disease-associated pathways with plausible involvement in bladder cancer,
      namely Regulation of actin cytoskeleton, Neurotrophin signalling pathway and
      Endocytosis. Systematic integration approaches allow to study the molecular
      context of individual features reported as associated with a clinical phenotype
      and could potentially help to improve the molecular mechanistic description of
      the disorder. 

PMID- 25569277
TI  - Expression and clinical significance of ghrelin in endometrial hyperplasia and
      carcinoma of Egyptian patients.
AB  - Endometrial carcinoma ranks the seventh most common malignant tumor worldwide.
      The distinction between atypical endometrial hyperplasia (AEH) and endometrial
      carcinoma, especially the well-differentiated grade, is particularly difficult
      with overlapping distinguishing criteria and small biopsy. Ghrelin is 28 amino
      acid peptide that is synthesized by gastric mucosa and is expressed in a variety
      of normal and tumor tissues. In endometrial tissue, it is expressed during the
      menstrual cycle, involved in the uterine development and cyclic growth. Data
      regarding role of Ghrelin in endometrial carcinoma are contradictory. In the
      present study, immunohistochemical expression of Ghrelin was evaluated in 55
      endometrioid carcinoma cases, as well as 26 endometrial hyperplasia cases. The
      relationship between Ghrelin expression and clinicopathologic features of
      endometrioid carcinoma was studied as well. Ghrelin loss or reduced expression
      was significantly related to endometrioid carcinoma, especially the well
      differentiated type, compared with AEH and EIN (p = 0.000 and 0.006,
      respectively). Ghrelin loss was also related to poorly differentiated histologic
      grades of endometrioid carcinoma (p = 0.04). Ghrelin loss is helpful in
      differentiation between AEH and EIN from endometrioid adenocarcinoma, especially
      the well-differentiated grade. It could be also related to poor differentiation.

PMID- 25569279
TI  - Six doctors are charged with taking kickbacks for sending patients to Chicago
      hospital for no reason.

PMID- 25569278
TI  - Reduction of urogenital schistosomiasis with an integrated control project in
      Sudan.
AB  - PURPOSE: Schistosomiasis remains a major public health concern in Sudan,
      particularly Schistosoma haematobium infection. This study presents the disease
      reduction outcomes of an integrated control program for schistosomiasis in Al
      Jabalain locality of White Nile State, Sudan from 2009 through 2011. METHODS: The
      total population of the project sites was 482,902, and the major target group for
      intervention among them was 78,615 primary school students. For the cross
      sectional study of the prevalence, urine and stool specimens were examined using
      the urine sedimentation method and the Kato cellophane thick smear method,
      respectively. To assess the impacts of health education for students and a
      drinking water supply facility at Al Hidaib village, questionnaire survey was
      done. RESULTS: The overall prevalence for S. haematobium and S. mansoni at
      baseline was 28.5% and 0.4%, respectively. At follow-up survey after 6-9 months
      post-treatment, the prevalence of S. haematobium infection was reduced to 13.5%
      (95% CI = 0.331-0.462). A higher reduction in prevalence was observed among
      girls, those with moderately infected status (around 20%), and residents in rural
      areas, than among boys, those with high prevalence (>40%), and residents in urban
      areas. After health education, increased awareness about schistosomiasis was
      checked by questionnaire survey. Also, a drinking water facility was constructed
      at Al Hidaib village, where infection rate was reduced more compared to that in a
      neighboring village within the same unit. However, we found no significant change
      in the prevalence of S. mansoni infection between baseline and follow-up survey
      (95% CI = 0.933-6.891). CONCLUSIONS: At the end of the project, the prevalence of
      S. haematobium infection was reduced by more than 50% in comparison with the
      baseline rate. Approximately 200,000 subjects had received either praziquantel
      therapy, health education, or supply of clean water. To consolidate the
      achievements of this project, the integrated intervention should be adapted
      continuously.

PMID- 25569280
TI  - Should children be evacuated during times of war?

PMID- 25569281
TI  - Exercise for osteoarthritis of the knee.
AB  - BACKGROUND: Knee osteoarthritis (OA) is a major public health issue because it
      causes chronic pain, reduces physical function and diminishes quality of life.
      Ageing of the population and increased global prevalence of obesity are
      anticipated to dramatically increase the prevalence of knee OA and its associated
      impairments. No cure for knee OA is known, but exercise therapy is among the
      dominant non-pharmacological interventions recommended by international
      guidelines. OBJECTIVES: To determine whether land-based therapeutic exercise is
      beneficial for people with knee OA in terms of reduced joint pain or improved
      physical function and quality of life. SEARCH METHODS: Five electronic databases
      were searched, up until May 2013. SELECTION CRITERIA: All randomised controlled
      trials (RCTs) randomly assigning individuals and comparing groups treated with
      some form of land-based therapeutic exercise (as opposed to exercise conducted in
      the water) with a non-exercise group or a non-treatment control group. DATA
      COLLECTION AND ANALYSIS: Three teams of two review authors independently
      extracted data, assessed risk of bias for each study and assessed the quality of
      the body of evidence for each outcome using the GRADE (Grades of Recommendation,
      Assessment, Development and Evaluation) approach. We conducted analyses on
      continuous outcomes (pain, physical function and quality of life) immediately
      after treatment and on dichotomous outcomes (proportion of study withdrawals) at
      the end of the study; we also conducted analyses on the sustained effects of
      exercise on pain and function (two to six months, and longer than six months).
      MAIN RESULTS: In total, we extracted data from 54 studies. Overall, 19 (20%)
      studies reported adequate random sequence generation and allocation concealment
      and adequately accounted for incomplete outcome data; we considered these studies
      to have an overall low risk of bias. Studies were largely free from selection
      bias, but research results may be vulnerable to performance and detection bias,
      as only four of the RCTs reported blinding of participants to treatment
      allocation, and, although most RCTs reported blinded outcome assessment, pain,
      physical function and quality of life were participant self-reported.High-quality
      evidence from 44 trials (3537 participants) indicates that exercise reduced pain
      (standardised mean difference (SMD) -0.49, 95% confidence interval (CI) -0.39 to 
      0.59) immediately after treatment. Pain was estimated at 44 points on a 0 to 100
      point scale (0 indicated no pain) in the control group; exercise reduced pain by
      an equivalent of 12 points (95% CI 10 to 15 points). Moderate-quality evidence
      from 44 trials (3913 participants) showed that exercise improved physical
      function (SMD -0.52, 95% CI -0.39 to -0.64) immediately after treatment. Physical
      function was estimated at 38 points on a 0 to 100-point scale (0 indicated no
      loss of physical function) in the control group; exercise improved physical
      function by an equivalent of 10 points (95% CI 8 to 13 points). High-quality
      evidence from 13 studies (1073 participants) revealed that exercise improved
      quality of life (SMD 0.28, 95% CI 0.15 to 0.40) immediately after treatment.
      Quality of life was estimated at 43 points on a 0 to 100-point scale (100
      indicated best quality of life) in the control group; exercise improved quality
      of life by an equivalent of 4 points (95% CI 2 to 5 points).High-quality evidence
      from 45 studies (4607 participants) showed a comparable likelihood of withdrawal
      from exercise allocation (event rate 14%) compared with the control group (event
      rate 15%), and this difference was not significant: odds ratio (OR) 0.93 (95% CI
      0.75 to 1.15). Eight studies reported adverse events, all of which were related
      to increased knee or low back pain attributed to the exercise intervention
      provided. No study reported a serious adverse event.In addition, 12 included
      studies provided two to six-month post-treatment sustainability data on 1468
      participants for knee pain and on 1279 (10 studies) participants for physical
      function. These studies indicated sustainability of treatment effect for pain
      (SMD -0.24, 95% CI -0.35 to -0.14), with an equivalent reduction of 6 (3 to 9)
      points on 0 to 100-point scale, and of physical function (SMD -0.15 95% CI -0.26
      to -0.04), with an equivalent improvement of 3 (1 to 5) points on 0 to 100-point
      scale.Marked variability was noted across included studies among participants
      recruited, symptom duration, exercise interventions assessed and important
      aspects of study methodology. Individually delivered programmes tended to result
      in greater reductions in pain and improvements in physical function, compared to
      class-based exercise programmes or home-based programmes; however between-study
      heterogeneity was marked within the individually provided treatment delivery
      subgroup. AUTHORS' CONCLUSIONS: High-quality evidence indicates that land-based
      therapeutic exercise provides short-term benefit that is sustained for at least
      two to six months after cessation of formal treatment in terms of reduced knee
      pain, and moderate-quality evidence shows improvement in physical function among
      people with knee OA. The magnitude of the treatment effect would be considered
      moderate (immediate) to small (two to six months) but comparable with estimates
      reported for non-steroidal anti-inflammatory drugs. Confidence intervals around
      demonstrated pooled results for pain reduction and improvement in physical
      function do not exclude a minimal clinically important treatment effect. Since
      the participants in most trials were aware of their treatment, this may have
      contributed to their improvement. Despite the lack of blinding we did not
      downgrade the quality of evidence for risk of performance or detection bias. This
      reflects our belief that further research in this area is unlikely to change the
      findings of our review.

PMID- 25569282
TI  - The importance of pathogen load.

PMID- 25569284
TI  - Simultaneous quantification of simvastatin and excipients in liposomes using near
      infrared spectroscopy and chemometry.
AB  - This work describes the development and validation of a near infrared (NIR)
      spectroscopy method coupled with an appropriate multivariate calibration
      algorithm for the simultaneous quantification of encapsulated drug, simvastatin
      (SIM) and excipients, L-alpha-phosphatidylcholine (LPC) and cholesterol (CHO) in
      liposomes. The development of calibration models for each compound was based on a
      D-optimal experimental design consisting of 63 standard mixtures containing LPC,
      CHO and SIM in chloroform. For each compound, different spectral pretreatment
      methods were applied in association with selected spectral regions. Partial least
      square regression (PLS) was performed using OPUS 6.5 software. Calibration set
      and cross-validation was carried out in order to select the best model to be used
      further. Straight line subtraction (SLS) was the best pre-treatment method for
      each compound, although the selected spectral regions were different. The method
      developed for each compound was validated in terms of linearity, trueness,
      precision and accuracy. Finally, the method has been successfully used for
      simultaneous quantification of SIM and excipients in liposomes. The encapsulation
      efficiency of SIM determined by this method was similar with that obtained by the
      use of reference HPLC method.

PMID- 25569283
TI  - Activation of parallel fiber feedback by spatially diffuse stimuli reduces signal
      and noise correlations via independent mechanisms in a cerebellum-like structure.
AB  - Correlations between the activities of neighboring neurons are observed
      ubiquitously across systems and species and are dynamically regulated by several
      factors such as the stimulus' spatiotemporal extent as well as by the brain's
      internal state. Using the electrosensory system of gymnotiform weakly electric
      fish, we recorded the activities of pyramidal cell pairs within the
      electrosensory lateral line lobe (ELL) under spatially localized and diffuse
      stimulation. We found that both signal and noise correlations were markedly
      reduced (>40%) under the latter stimulation. Through a network model
      incorporating key anatomical features of the ELL, we reveal how activation of
      diffuse parallel fiber feedback from granule cells by spatially diffuse
      stimulation can explain both the reduction in signal as well as the reduction in
      noise correlations seen experimentally through independent mechanisms. First, we
      show that burst-timing dependent plasticity, which leads to a negative image of
      the stimulus and thereby reduces single neuron responses, decreases signal but
      not noise correlations. Second, we show trial-to-trial variability in the
      responses of single granule cells to sensory input reduces noise but not signal
      correlations. Thus, our model predicts that the same feedback pathway can
      simultaneously reduce both signal and noise correlations through independent
      mechanisms. To test this prediction experimentally, we pharmacologically
      inactivated parallel fiber feedback onto ELL pyramidal cells. In agreement with
      modeling predictions, we found that inactivation increased both signal and noise
      correlations but that there was no significant relationship between magnitude of
      the increase in signal correlations and the magnitude of the increase in noise
      correlations. The mechanisms reported in this study are expected to be generally
      applicable to the cerebellum as well as other cerebellum-like structures. We
      further discuss the implications of such decorrelation on the neural coding
      strategies used by the electrosensory and by other systems to process natural
      stimuli. 

PMID- 25569285
TI  - High-performance liquid chromatography-tandem mass spectrometry method for the
      determination of perampanel, a novel alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor antagonist in human plasma.
AB  - Perampanel (Fycompa((r))) is a novel alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor antagonist registered for the adjunctive
      treatment of patients (>=12 years) with refractory partial onset seizures. In
      order to support clinical trials, as well as therapeutic drug monitoring, a
      sensitive bioanalytical method for the determination of perampanel concentrations
      in human plasma was established and validated using liquid chromatography with
      tandem mass spectrometry. Perampanel and an internal standard were extracted from
      human plasma (100 MUL) by liquid extraction using methyl t-butyl ether, then
      evaporated and reconstituted. The chromatographic separation was conducted on a
      C8 column with isocratic elution at a flow rate of 0.2 mL/min. The established
      method showed linearity in the range 0.25-200 ng/mL with correlation coefficients
      of >0.99 that could be extended 10-fold as validated by dilution integrity
      analyses. No significant endogenous peaks were detected in the elution of
      analytes in blank human plasma and no significant matrix effect was observed. The
      intra- and inter-batch reproducibility analyses demonstrated accuracy and
      precision within the acceptance criteria. To check the impact of anti-epileptic
      drugs on the perampanel assay, accuracy, precision, and specificity were assessed
      in the presence of 14 anti-epileptic drugs. No anti-epileptic drugs at clinically
      relevant levels showed a significant impact on the perampanel assay.

PMID- 25569286
TI  - Emerging field of metabolomics: big promise for cancer biomarker identification
      and drug discovery.
AB  - Most cancers are lethal and metabolic alterations are considered a hallmark of
      this deadly disease. Genomics and proteomics have contributed vastly to
      understand cancer biology. Still there are missing links as downstream to them
      molecular divergence occurs. Metabolomics, the omic science that furnishes a
      dynamic portrait of metabolic profile is expected to bridge these gaps and boost
      cancer research. Metabolites being the end products are more stable than mRNAs or
      proteins. Previous studies have shown the efficacy of metabolomics in identifying
      biomarkers associated with diagnosis, prognosis and treatment of cancer.
      Metabolites are highly informative about the functional status of the biological
      system, owing to their proximity to organismal phenotypes. Scores of publications
      have reported about high-throughput data generation by cutting-edge analytic
      platforms (mass spectrometry and nuclear magnetic resonance). Further
      sophisticated statistical softwares (chemometrics) have enabled meaningful
      information extraction from the metabolomic data. Metabolomics studies have
      demonstrated the perturbation in glycolysis, tricarboxylic acid cycle, choline
      and fatty acid metabolism as traits of cancer cells. This review discusses the
      latest progress in this field, the future trends and the deficiencies to be
      surmounted for optimally implementation in oncology. The authors scoured through
      the most recent, high-impact papers archived in Pubmed, ScienceDirect, Wiley and
      Springer databases to compile this review to pique the interest of researchers
      towards cancer metabolomics. 

PMID- 25569287
TI  - Simultaneous determination of six triterpenic acids in some Chinese medicinal
      herbs using ultrasound-assisted dispersive liquid-liquid microextraction and high
      performance liquid chromatography with fluorescence detection.
AB  - A novel analytical method was developed for simultaneous determination of six
      triterpenic acids using ultrasound-assisted dispersive liquid-liquid
      microextraction (UA-DLLME) follow by high-performance liquid chromatography
      (HPLC) with fluorescence detection. Six triterpenic acids (ursolic acid,
      oleanolic acid, betulinic acid, maslinic acid, betulonic acid and corosolic acid)
      were extracted by UA-DLLME using chloroform and acetone as the extraction and
      disperser solvents, respectively. After the extraction and nitrogen flushing, the
      extracts were rapidly derivatized with 2-(12,13-dihydro-7H-dibenzo[a,g]carbazol-7
      yl)ethyl4-methylbenzenesulfonate. The main experimental parameters affecting
      extraction efficiency and derivatization yield were investigated and optimized by
      response surface methodology (RSM) combined with Box-Behnken design (BBD). The
      limits of detection (LODs) and the limits of quantification (LOQs) were in the
      range of 0.95-1.36 ng mL(-1) and 3.17-4.55 ng mL(-1), respectively. Under the
      optimum conditions, the method has been successfully applied for the analysis of
      triterpenic acids in six different traditional Chinese medicinal herbs.

PMID- 25569289
TI  - Most known fossil fuel reserves must remain unused to meet climate change
      targets.

PMID- 25569288
TI  - Protective efficacy of centralized and polyvalent envelope immunogens in an
      attenuated equine lentivirus vaccine.
AB  - Lentiviral Envelope (Env) antigenic variation and related immune evasion present
      major hurdles to effective vaccine development. Centralized Env immunogens that
      minimize the genetic distance between vaccine proteins and circulating viral
      isolates are an area of increasing study in HIV vaccinology. To date, the
      efficacy of centralized immunogens has not been evaluated in the context of an
      animal model that could provide both immunogenicity and protective efficacy data.
      We previously reported on a live-attenuated (attenuated) equine infectious anemia
      (EIAV) virus vaccine, which provides 100% protection from disease after virulent,
      homologous, virus challenge. Further, protective efficacy demonstrated a
      significant, inverse, linear relationship between EIAV Env divergence and
      protection from disease when vaccinates were challenged with viral strains of
      increasing Env divergence from the vaccine strain Env. Here, we sought to
      comprehensively examine the protective efficacy of centralized immunogens in our
      attenuated vaccine platform. We developed, constructed, and extensively tested a
      consensus Env, which in a virulent proviral backbone generated a fully
      replication-competent pathogenic virus, and compared this consensus Env to an
      ancestral Env in our attenuated proviral backbone. A polyvalent attenuated
      vaccine was established for comparison to the centralized vaccines. Additionally,
      an engineered quasispecies challenge model was created for rigorous assessment of
      protective efficacy. Twenty-four EIAV-naive animals were vaccinated and
      challenged along with six-control animals six months post-second inoculation. Pre
      challenge data indicated the consensus Env was more broadly immunogenic than the
      Env of the other attenuated vaccines. However, challenge data demonstrated a
      significant increase in protective efficacy of the polyvalent vaccine. These
      findings reveal, for the first time, a consensus Env immunogen that generated a
      fully-functional, replication-competent lentivirus, which when experimentally
      evaluated, demonstrated broader immunogenicity that does not equate to higher
      protective efficacy. 

PMID- 25569291
TI  - Growth of wafer-scale MoS2 monolayer by magnetron sputtering.
AB  - The two-dimensional layer of molybdenum disulfide (MoS2) exhibits promising
      prospects in the applications of optoelectronics and valleytronics. Herein, we
      report a successful new process for synthesizing wafer-scale MoS2 atomic layers
      on diverse substrates via magnetron sputtering. Spectroscopic and microscopic
      results reveal that these synthesized MoS2 layers are highly homogeneous and
      crystallized; moreover, uniform monolayers at wafer scale can be achieved. Raman
      and photoluminescence spectroscopy indicate comparable optical qualities of these
      as-grown MoS2 with other methods. The transistors composed of the MoS2 film
      exhibit p-type performance with an on/off current ratio of ~10(3) and hole
      mobility of up to ~12.2 cm(2) V(-1) s(-1). The strategy reported herein paves new
      ways towards the large scale growth of various two-dimensional semiconductors
      with the feasibility of controllable doping to realize desired p- or n-type
      devices. 

PMID- 25569290
TI  - Mycobacterium africanum is associated with patient ethnicity in Ghana.
AB  - Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex
      (MTBC) and an important cause of human tuberculosis in West Africa that is rarely
      observed elsewhere. Here we genotyped 613 MTBC clinical isolates from Ghana, and
      searched for associations between the different phylogenetic lineages of MTBC and
      patient variables. We found that 17.1% (105/613) of the MTBC isolates belonged to
      M. africanum, with the remaining belonging to M. tuberculosis sensu stricto. No
      M. bovis was identified in this sample. M. africanum was significantly more
      common in tuberculosis patients belonging to the Ewe ethnic group (adjusted odds
      ratio: 3.02; 95% confidence interval: 1.67-5.47, p<0.001). Stratifying our
      analysis by the two phylogenetic lineages of M. africanum (i.e. MTBC Lineages 5
      and 6) revealed that this association was mainly driven by Lineage 5 (also known
      as M. africanum West Africa 1). Our findings suggest interactions between the
      genetic diversity of MTBC and human diversity, and offer a possible explanation
      for the geographical restriction of M. africanum to parts of West Africa. 

PMID- 25569292
TI  - Development of a PCR-Based Method for Detection of Delphinium Species in Poisoned
      Cattle.
AB  - Toxic plants such as Delphinium spp. (i.e., larkspur) are a significant cause of
      livestock losses worldwide. Correctly determining the causative agent responsible
      for the death of an animal, whether by disease, poisonous plant, or other means,
      is critical in developing strategies to prevent future losses. The objective of
      this study was to develop an alternative diagnostic tool to microscopy and
      analytical chemistry to determine whether a particular poisonous plant was
      ingested. Polymerase chain reaction (PCR) is a tool that may allow detection of
      the genetic material from a specific plant within a complex matrix such as rumen
      contents. A pair of oligonucleotide primers specific to Delphinium spp. (i.e.,
      larkspur) was developed; using these primers, a PCR product was detected in
      samples from an in vivo, in vitro, and in vivo/in vitro coupled digestion of
      Delphinium occidentale. Lastly, larkspur was detected in a matrix of ruminal
      material where the amount of larkspur was far less than what one would expect to
      find in the rumen contents of a poisoned animal. The PCR-based technique holds
      promise to diagnose larkspur and perhaps other toxic plant caused losses.

PMID- 25569293
TI  - The connection between seasonal allergies, food allergies, and rhinosinusitis:
      what is the evidence?
AB  - PURPOSE OF REVIEW: Rhinosinusitis affects an estimated one in seven adults in the
      United States. Otolaryngologists are intimately involved in the care of patients
      with rhinosinusitis and other upper airway inflammatory conditions through
      procedures such as endoscopic sinus surgery and, therefore, would benefit from a
      deeper understanding of the associated comorbidities and their management. Recent
      evidence has suggested several connections between the underlying disease of
      rhinosinusitis, seasonal allergies, and food allergies. The authors of the
      present review seek to provide a focused analysis of the recent literature with
      respect to epidemiology, pathophysiology, and treatment options concerning these
      conditions. RECENT FINDINGS: Evidence has connected the function of filaggrin, a
      skin barrier protein, with the pathogenesis of allergic rhinosinusitis and food
      allergy. Additionally, decreased levels of regulatory B cells and T cells are
      associated with and play a role in atopic disease. Overlapping treatment
      modalities between these conditions suggest similar conclusions. SUMMARY: Future
      research into the role of the skin barrier, regulatory immune cell functioning,
      transforming growth factor-beta, and other cytokine signaling, and treatment
      options such as omalizumab and azelastine is likely to have profound impact on
      clinicians' management of patients with these disorders and their comorbidities.

PMID- 25569294
TI  - An algorithmic approach to the evaluation and treatment of olfactory disorders.
AB  - PURPOSE OF REVIEW: To review the current evidence in diagnosing olfactory
      disorders and suggest an algorithmic approach to patients with relevant
      complaints. RECENT FINDINGS: New literature suggests that the incidence of
      olfactory loss increases with age. Age-associated olfactory loss is often
      multifactorial and requires careful history and physical exam. Psychophysical
      tests have a role in screening patients at risk for Parkinson's and Alzheimer's
      disease, but there is lack of evidence regarding timing and patient selection.
      Prediction of olfactory improvement in patients with chronic rhinosinusitis (CRS)
      is difficult with variable results from different studies. Olfactory training is
      suggested to be an emerging modality in patients with postinfectious olfactory
      loss. SUMMARY: There is no standard treatment for olfactory loss. Each patient
      must be approached individually based on the suspected cause. Patients with CRS
      may require medical management and surgical treatment for alleviation of their
      olfactory dysfunction.

PMID- 25569295
TI  - The role of antibiotics in endoscopic sinus surgery.
AB  - PURPOSE OF REVIEW: To review and discuss recent literature regarding the use of
      antibiotics in relation to endoscopic sinus surgery (ESS), including
      perioperative antibiotics, postoperative antibiotics, and antibiotic usage in the
      setting of postoperative packing. RECENT FINDINGS: Perioperative antibiotics are
      not recommended by the American Society of Health-System Pharmacists. The
      necessity of antibiotics following ESS is a heavily debated topic. Most studies
      show little to no improvement in outcomes. Significant improvement in quality-of
      life outcomes and endoscopic scoring appears limited to the early postoperative
      period using conventional postoperative antibiotics. Prolonged macrolide therapy
      may improve long-term outcomes. There is no convincing evidence to show the need
      for antibiotics in the setting of postoperative packing. SUMMARY: The available
      evidence regarding antibiotic use in relation to ESS overall fails to demonstrate
      routine benefit; however, the studies have various limitations. Overall, future,
      well designed, large-scale prospective studies would be beneficial to direct
      appropriate antibiotic use, whether systemic or topical, in relation to ESS.

PMID- 25569296
TI  - Gliomatosis cerebri having a poor performance status without recurrence after
      radiotherapy: a single institutional experience.
AB  - OBJECTIVE: Radiotherapy (RT) has been advocated for gliomatosis cerebri (GC) to
      delay tumor progression. However, patients with GC may experience poor
      performance status without recurrence after RT. Herein, we reviewed the responses
      of patients with GC treated with RT. MATERIALS AND METHODS: Seventeen patients
      with diffuse radiologic infiltration of more than two cerebral lobes and
      diagnosed as having grade II (N=12) or III (N=5) glioma were treated with a mean
      radiation dose of 51.8 Gy (range, 42-59.4 Gy). The mean radiation volume to a
      mean marginal dose of 42.8 Gy (range, 36-45 Gy) was 693.4 cc (range, 316.5-1279.6
      cc), which was 45.3% of the mean whole brain volume. We reviewed the clinical
      prognostic factors related to progression-free survival (PFS) and overall
      survival (OS) in all patients and described characteristics of patients with poor
      performance (Eastern Cooperative Oncology Group performance scale 3-4) without
      recurrence. RESULTS: In all patients, the median PFS was 12.3 months, and
      oligodendroglial pathology (p=0.002) and non-enhanced tumor (p=0.002) were
      associated with an improved PFS. The median OS was 39.3 months, and young age and
      adjuvant chemotherapy were associated with improved OS (p=0.022 and 0.002,
      respectively). Based on multivariate analysis, adjuvant chemotherapy was
      significantly associated with a longer OS (p=0.012; hazard ratio=0.099; 95% CI,
      0.016-0.596). Five patients (29.4%) showed poor performance without recurrence.
      The median age of these 5 patients was 65 years (range, 60-75 years). The mean
      radiation volume to a mean marginal dose of 41 Gy (range, 36-45 Gy) was 539.9 cc
      (range, 255.5-983.1 cc). The pathologic diagnosis was grade II glioma in 2
      patients and grade III in 3 patients. The median OS was 10.0 months (range, 8.2
      45.9 months). CONCLUSIONS: Some GC patients, especially the elderly, might have a
      poor performance status without recurrence after RT of a larger radiation field.

PMID- 25569298
TI  - Cigarette smoking and lung obstruction among adults aged 40-79: United States,
      2007-2012.
AB  - During 2007-2012, about 46% of U.S. adults aged 40-79 with lung obstruction
      currently smoked cigarettes. This was more than double the smoking rate for those
      without lung obstruction (19.8%). In the United States, a greater percentage of
      men (20.5%) than women (15.3%) were current cigarette smokers in 2013. Some
      studies have suggested that women are more susceptible than men to the effects of
      tobacco smoke. Since 2000, the number of women dying from COPD has exceeded the
      number of men dying from the disease. In the present report, a similar percentage
      of men and women overall, and at each level of lung obstruction severity,
      currently smoked cigarettes. Notable differences were seen in smoking rates by
      race and Hispanic origin. Among adults aged 40-79 with mild lung obstruction, a
      significantly greater percentage of non-Hispanic black adults currently smoked
      cigarettes compared with the two other race and Hispanic origin groups. With
      moderate or worse lung obstruction, however, a significantly greater percentage
      of non-Hispanic white adults currently smoked cigarettes compared with those in
      the other race and Hispanic origin groups. Smoking rates among those with lung
      obstruction also varied by education, with progressively higher rates of smoking
      among those with decreasing levels of education. This inverse relationship
      between smoking and education level is consistent across all severity levels of
      lung obstruction. Smoking tobacco can increase respiratory symptoms, loss of lung
      function, and the progression of COPD. The data presented here show that during
      2007-2012, almost one-half of U.S. adults aged 40-79 with lung obstruction
      currently smoked cigarettes.

PMID- 25569297
TI  - Spontaneous regression of neuro-ophthalmological sarcoidosis.

PMID- 25569300
TI  - Cation exchange properties of zeolites in hyper alkaline aqueous media.
AB  - Construction of multibarrier concrete based waste disposal sites and management
      of alkaline mine drainage water requires cation exchangers combining excellent
      sorption properties with a high stability and predictable performance in hyper
      alkaline media. Though highly selective organic cation exchange resins have been
      developed for most pollutants, they can serve as a growth medium for bacterial
      proliferation, impairing their long-term stability and introducing unpredictable
      parameters into the evolution of the system. Zeolites represent a family of
      inorganic cation exchangers, which naturally occur in hyper alkaline conditions
      and cannot serve as an electron donor or carbon source for microbial
      proliferation. Despite their successful application as industrial cation
      exchangers under near neutral conditions, their performance in hyper alkaline,
      saline water remains highly undocumented. Using Cs(+) as a benchmark element,
      this study aims to assess the long-term cation exchange performance of zeolites
      in concrete derived aqueous solutions. Comparison of their exchange properties in
      alkaline media with data obtained in near neutral solutions demonstrated that the
      cation exchange selectivity remains unaffected by the increased hydroxyl
      concentration; the cation exchange capacity did however show an unexpected
      increase in hyper alkaline media. 

PMID- 25569299
TI  - Aptamer-based detection of disease biomarkers in mouse models for chagas drug
      discovery.
AB  - Drug discovery initiatives, aimed at Chagas treatment, have been hampered by the
      lack of standardized drug screening protocols and the absence of simple pre
      clinical assays to evaluate treatment efficacy in animal models. In this study,
      we used a simple Enzyme Linked Aptamer (ELA) assay to detect T. cruzi biomarker
      in blood and validate murine drug discovery models of Chagas disease. In two mice
      models, Apt-29 ELA assay demonstrated that biomarker levels were significantly
      higher in the infected group compared to the control group, and upon Benznidazole
      treatment, their levels reduced. However, biomarker levels in the infected
      treated group did not reduce to those seen in the non-infected treated group,
      with 100% of the mice above the assay cutoff, suggesting that parasitemia was
      reduced but cure was not achieved. The ELA assay was capable of detecting
      circulating biomarkers in mice infected with various strains of T. cruzi
      parasites. Our results showed that the ELA assay could detect residual
      parasitemia in treated mice by providing an overall picture of the infection in
      the host. They suggest that the ELA assay can be used in drug discovery
      applications to assess treatment efficacy in-vivo. 

PMID- 25569302
TI  - Dielectric constant of liquids confined in the extended nanospace measured by a
      streaming potential method.
AB  - Understanding liquid structure and the electrical properties of liquids confined
      in extended nanospaces (10-1000 nm) is important for nanofluidics and
      nanochemistry. To understand these liquid properties requires determination of
      the dielectric constant of liquids confined in extended nanospaces. A novel
      dielectric constant measurement method has thus been developed for extended
      nanospaces using a streaming potential method. We focused on the nonsteady-state
      streaming potential in extended nanospaces and successfully measured the
      dielectric constant of liquids within them without the use of probe molecules.
      The dielectric constant of water was determined to be significantly reduced by
      about 3 times compared to that of the bulk. This result contributes key
      information toward further understanding of the chemistry and fluidics in
      extended nanospaces. 

PMID- 25569301
TI  - Defect structure analysis of heterointerface between Pt and CeOx promoter on Pt
      electro-catalyst.
AB  - Pt-CeOx/C (1.5 <= x <= 2) electro-catalyst is one of the most promising cathode
      materials for use in polymer membrane electrolyte fuel cells. To clarify the
      microstructure of Pt-CeOx heterointerface, we prepared Pt-loaded CeOx thin film
      on conductive SrTiO3 single crystal substrate by using a stepwise process of
      pulse laser deposition method for the preparation of epitaxial growth CeOx film
      followed by an impregnation method which loaded the Pt particles on the CeOx
      film. The electrochemistry observed for the Pt-loaded CeOx thin film on the
      conductive single crystal substrate was examined by using cyclic voltammetry in
      0.5 M H2SO4 aqueous solution, and a cross-sectional image of the aforementioned
      Pt-CeOx thin film electrode was observed using a transmission electron
      microscope. The electrochemistry observed for Pt-CeOx thin film electrode clearly
      showed the promotion effect of CeOx. Also, the microanalysis indicated that
      unique, large clusters that consisted of C-type rare-earth-like structures were
      formed in the Pt-CeOx interface by a strong interaction between Pt and CeOx. The
      present combination analysis of the electrochemistry, microanalysis, and
      atomistic simulation indicates that the large clusters (i.e., 12 (PtCe''-Vo(**))
      + 2 (PtCe''-2Vo(**)-2CeCe')) that were formed into the Pt-CeOx interface promoted
      the charge transfer between Pt surface and CeOx, suggesting that the oxygen
      reduction reaction activity on Pt can be maximized by fabrication of C-type rare
      earth-like structure that consists of the aforementioned large clusters in the Pt
      CeOx interfaces. 

PMID- 25569303
TI  - Geographic expansion of the invasive mosquito Aedes albopictus across Panama-
      implications for control of dengue and Chikungunya viruses.

PMID- 25569304
TI  - Facile fabrication of a silver dendrite-integrated chip for surface-enhanced
      Raman scattering.
AB  - A facile approach to fabricating a surface-enhanced Raman scattering (SERS)
      active chip by integrating silver dendrites with copper substrate through a one
      step process was explored. The structures of dendrites were synthesized and
      controlled by an AgNO3/PVP aqueous system, and the fabrication parameters amount
      of AgNO3/PVP and reaction time were systematically investigated. The optimized
      silver dendrites, closely aggregated on the surface of the copper chip, exhibited
      high SERS activity for detecting rhodamine 6G at a concentration as low as 3.2 *
      10(-11) M. Meanwhile, the prepared SERS-active chip displayed a high thermal
      stability and good reproducibility. Moreover, the potential application for
      analysis of polycyclic aromatic hydrocarbons was demonstrated by detection of
      fluoranthene at a low concentration of 4.5 * 10(-10) M. This SERS-active chip
      prepared by the convenient and high-yield method would be a promising means for
      rapid detection under field conditions. 

PMID- 25569307
TI  - Ionically cross-linked poly(allylamine) as a stimulus-responsive underwater
      adhesive: ionic strength and pH effects.
AB  - Gel-like coacervates that adhere to both hydrophilic and hydrophobic substrates
      under water have recently been prepared by ionically cross-linking
      poly(allylamine) (PAH) with pyrophosphate (PPi) and tripolyphosphate (TPP). Among
      the many advantages of these underwater adhesives (which include their simple
      preparation and low cost) is their ability to dissolve on demand when exposed to
      high or low pH. To further analyze their stimulus-responsive properties, we have
      investigated the pH and ionic strength effects on the formation, rheology and
      adhesion of PAH/PPi and PAH/TPP complexes. The ionic cross-linker concentrations
      needed to form these adhesives decreased with increasing pH and ionic strength
      (although the complexes ceased to form when the parent solution pH exceeded ca.
      8.5; i.e., the effective pKa of PAH). Once formed, their ionic cross-links were
      most stable (as inferred from their relaxation times) at near-neutral or slightly
      alkaline pH values (of roughly 6.5-9) and at low ionic strengths. The decrease in
      ionic cross-link stability within complexes prepared at other pH values and at
      elevated (150-300 mM) NaCl concentrations diminished both the strength and
      longevity of adhesion (although, under most conditions tested, the short-term
      tensile adhesion strengths remained above 10(5) Pa). Additionally, the
      sensitivity of PAH/PPi and PAH/TPP complexes to ionic strength was demonstrated
      as a potential route to injectable adhesive design (where spontaneous adhesive
      formation was triggered via injection of low-viscosity, colloidal PAH/TPP
      dispersions into phosphate buffered saline). Thus, while the sensitivity of
      ionically cross-linked PAH networks to pH and ionic strength can weaken their
      adhesion, it can also impart them with additional functionality, such as
      minimally invasive, injectable delivery, and ability to form and dissolve their
      bonds on demand. 

PMID- 25569306
TI  - Co-infection alters population dynamics of infectious disease.
AB  - Co-infections by multiple pathogen strains are common in the wild. Theory
      predicts co-infections to have major consequences for both within- and between
      host disease dynamics, but data are currently scarce. Here, using common garden
      populations of Plantago lanceolata infected by two strains of the pathogen
      Podosphaera plantaginis, either singly or under co-infection, we find the highest
      disease prevalence in co-infected treatments both at the host genotype and
      population levels. A spore-trapping experiment demonstrates that co-infected
      hosts shed more transmission propagules than singly infected hosts, thereby
      explaining the observed change in epidemiological dynamics. Our experimental
      findings are confirmed in natural pathogen populations-more devastating epidemics
      were measured in populations with higher levels of co-infection. Jointly, our
      results confirm the predictions made by theoretical and experimental studies for
      the potential of co-infection to alter disease dynamics across a large host
      pathogen metapopulation. 

PMID- 25569305
TI  - Functional interplay between the 53BP1-ortholog Rad9 and the Mre11 complex
      regulates resection, end-tethering and repair of a double-strand break.
AB  - The Mre11-Rad50-Xrs2 nuclease complex, together with Sae2, initiates the 5'-to-3'
      resection of Double-Strand DNA Breaks (DSBs). Extended 3' single stranded DNA
      filaments can be exposed from a DSB through the redundant activities of the Exo1
      nuclease and the Dna2 nuclease with the Sgs1 helicase. In the absence of Sae2,
      Mre11 binding to a DSB is prolonged, the two DNA ends cannot be kept tethered,
      and the DSB is not efficiently repaired. Here we show that deletion of the yeast
      53BP1-ortholog RAD9 reduces Mre11 binding to a DSB, leading to Rad52 recruitment
      and efficient DSB end-tethering, through an Sgs1-dependent mechanism. As a
      consequence, deletion of RAD9 restores DSB repair either in absence of Sae2 or in
      presence of a nuclease defective MRX complex. We propose that, in cells lacking
      Sae2, Rad9/53BP1 contributes to keep Mre11 bound to a persistent DSB, protecting
      it from extensive DNA end resection, which may lead to potentially deleterious
      DNA deletions and genome rearrangements. 

PMID- 25569308
TI  - A high-throughput screen reveals new small-molecule activators and inhibitors of
      pantothenate kinases.
AB  - Pantothenate kinase (PanK) is a regulatory enzyme that controls coenzyme A (CoA)
      biosynthesis. The association of PanK with neurodegeneration and diabetes
      suggests that chemical modifiers of PanK activity may be useful therapeutics. We
      performed a high throughput screen of >520000 compounds from the St. Jude
      compound library and identified new potent PanK inhibitors and activators with
      chemically tractable scaffolds. The HTS identified PanK inhibitors exemplified by
      the detailed characterization of a tricyclic compound (7) and a preliminary SAR.
      Biophysical studies reveal that the PanK inhibitor acts by binding to the ATP
      enzyme complex. 

PMID- 25569311
TI  - A painful red eye.

PMID- 25569312
TI  - An adolescent with a swollen nerve.

PMID- 25569313
TI  - Angioid streaks in association with sickle thalassemia trait.

PMID- 25569314
TI  - Optic nerve pit and associated macular detachment.

PMID- 25569315
TI  - Trans-synaptic degeneration of lateral geniculate nuclei following remote loss of
      right eye.

PMID- 25569317
TI  - Posterior nodular scleritis.

PMID- 25569316
TI  - Congenital cataract.

PMID- 25569318
TI  - Retinopathy of prematurity evolution after laser treatment: Retcam findings.

PMID- 25569319
TI  - A 360 degrees  giant retinal tear in Stickler syndrome.

PMID- 25569320
TI  - Prominent Mittendorf spot.

PMID- 25569321
TI  - Making the Middle Count: Three Tools to Improve Throughput for a Better Patient
      Experience.
AB  - This article discusses three ways in which dramatic improvements in middle flow,
      or examination-to-disposition time, can be driven by emergency department (ED)
      nursing leadership. By operationalizing a "results pending" area, low-acuity
      patients who are unlikely to be admitted can await diagnostic results or be
      actively monitored by a dedicated nurse, ED rooms and beds may be reserved for
      higher acuity patients. Monthly operational stakeholder meetings can provide a
      consistent opportunity to track, monitor, and improve flow while also celebrating
      successes and identifying needed performance improvements based on objective
      metrics for shared goals. Internal customer rounding is a process that serves as
      effective follow-up from the stakeholder meeting to ensure aligned behaviors to
      meet identified goals. Frequency of rounding is identified during the stakeholder
      meeting. By using these three tools, ED stakeholders can effectively focus on
      solutions instead of barriers to improving middle flow.This is an open-access
      article distributed under the terms of the Creative Commons Attribution
      NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and
      share the work provided it is properly cited. The work cannot be changed in any
      way or used commercially.

PMID- 25569322
TI  - Increase in the expression of inducible nitric oxide synthase on exposure to
      bisphenol A: a possible cause for decline in steroidogenesis in male mice.
AB  - Bisphenol A (BPA) is a well-known plasticizer and xenoestrogen that is
      responsible for many acquired reproductive difficulties, especially in men.
      Despite the prevalence of BPA in society, the mechanism behind reproductive
      deficits remains elusive. The present study investigates the mode of BPA's action
      by evaluating its effect on the expression of inducible nitric oxide synthase
      (iNOS) and steriodogenic acute regulatoryprotein (StAR) in male mice testis.
      Swiss albino mice were treated with a range BPA concentrations of 0.5, 50 and
      100MUg/kg body weight/day intraperitoneally for 60 days. Several markers of
      oxidative stress and male fertility were investigated. Nitrite levels,
      malondialdehyde levels and testicular injury scores were elevated whereas the
      sperm count, serum testosterone levels and catalase activity were reduced in the
      BPA groups. Mechanistically, an increase in iNOS expression was observed in the
      testis whereas the expression of the StAR was down regulated in the BPA treated
      mouse. These results suggest that BPA induces oxidative stress by altering the
      expression of iNOS, which consequently leads to the down regulation of StAR
      expression in the testis of male mouse. 

PMID- 25569323
TI  - Effect of Khat on apoptosis and related gene Smac/DIABLO expression in the
      cerebral cortex of rats following transient focal ischemia.
AB  - BACKGROUND: The leaves of the Khat shrub contain the major alkaloid compounds
      (cathinone) and cathine. These compounds can induce apoptosis and exacerbate the
      acute cerebral infarction, but the underlying mechanism is poorly understood. The
      present study aimed to investigate the effects of Khat treatment on the
      expression and cellular localization of Smac/Diablo (second mitochondrial
      activator of caspase) in the cortex of ischemic rat brain. METHODS: Adult male
      Sprague-Dawley rats were administered Khat (3g/kg) twice daily for 4 weeks, then
      underwent left middle cerebral artery occlusion (MCAO) for 2h and reperfusion for
      3, 6 and 12h, respectively. The infarction area was evaluated with 2,3,5
      triphenyltetrazolium chloride (TTC) staining. Apoptosis was assessed by terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL).
      Smac/DIABLO expression levels in experimental and control groups were examined by
      immunohistochemistry and Western blot. RESULTS: Khat significantly exacerbates
      the neurological damage compared with control (p<0.05). In addition, Khat
      treatment significantly increased the number of TUNEL-positive cells 3h (p<0.01)
      and 12h (p<0.05) after reperfusion. Ischemia/reperfusion enhanced the release of
      Smac/DIABLO from the mitochondria to the cytosol after reperfusion. Such release
      of Smac/DIABLO was elevated after the rats were pretreated with Khat.
      CONCLUSIONS: Our results indicate that Khat treatment can induce apoptosis
      through enhancing the release of Smac/DIABLO from the mitochondria to the cytosol
      after transient focal ischemia which may be an important mechanism of Khat
      neurotoxicity. Therefore, Khat chewing should be avoided by people who have
      cerebrovascular problems.

PMID- 25569325
TI  - Electrochemical preparation and characterization of polypyrrole/stainless steel
      electrodes decorated with gold nanoparticles.
AB  - The electrosynthesis and characterization of polypyrrole(PPy)/stainless steel
      electrodes decorated with gold nanoparticles and the performance of the composite
      electrode for sensing applications is described. PPy films were grown in
      potassium perchlorate and sodium salicylate solutions under comparable
      electropolymerization conditions. Polymer films prepared in the presence of
      perchlorate ions exhibited worm-like structures, whereas columnar structures were
      obtained in salicylate-containing solutions. Voltammetric response of PPy films
      prepared in salicylate solutions was more reversible. PPy films were decorated
      with gold nanoparticles obtained by a double step potentiostatic
      electrodeposition routine that allowed fine control of deposit characteristics.
      Analysis of deposits was performed by means of SEM and confocal Raman
      spectroscopy. The electrocatalytic activity of the Au/PPy electrodes was assessed
      for the electro-oxidation of hydrazine and hydroxylamine. Results showed a
      successful optimization of the route of synthesis that rendered nanocomposite
      electrode materials with promising applications in electrochemical sensing. 

PMID- 25569324
TI  - Cardiometabolic risk factor response to a lifestyle intervention: a randomized
      trial.
AB  - BACKGROUND: Strategies to increase adherence to national dietary and physical
      activity (PA) guidelines to improve the health in regions such as the Lower
      Mississippi Delta (LMD) of the United States are needed. Here we explore the
      cardiometabolic responses to an education and behavior change intervention among
      overweight and obese adults that adapted the 2010 Dietary Guidelines (DG), with
      and without a PA component. METHODS: White and African American overweight and
      obese adults were randomized to a DG group (n=61) or a DG+PA group (n=60). Both
      groups received a 12-week dietary education and behavior change intervention, and
      the DG+PA group also received a PA education and behavior change intervention
      with a pedometer. Changes in individual risk factors (blood pressure, fasting
      glucose, triglycerides, high-density lipoprotein cholesterol, and low-density
      lipoprotein cholesterol) and a continuous cardiometabolic risk score were
      determined. General linear models compared mean changes between groups, adjusting
      for covariates. RESULTS: No main effect of intervention group was found in
      completers (n=99) and those who engaged with >=80% of the intervention (n=83) for
      individual risk factors or the continuous risk score. Pooling both groups, those
      with higher baseline risk factor values realized greater improvements in
      individual risk factors. CONCLUSIONS: Adapting DG did not produce any
      cardiometabolic benefits, even with a PA component. Although the sample was
      ostensibly healthy, they were all overweight to mildly obese (body mass index of
      25-34.9 kg/m(2)) and participants with higher baseline risk factor values showed
      more improvements. Adherence to longer-term behavior change may elicit changes in
      risk profile, so this should be explored.

PMID- 25569328
TI  - Potential effect of the presence of gray crescent on analysis of optic disc and
      retinal nerve fiber layer defects.

PMID- 25569326
TI  - An intracellular transcriptomic atlas of the giant coenocyte Caulerpa taxifolia.
AB  - Convergent morphologies have arisen in plants multiple times. In non-vascular and
      vascular land plants, convergent morphology in the form of roots, stems, and
      leaves arose. The morphology of some green algae includes an anchoring holdfast,
      stipe, and leaf-like fronds. Such morphology occurs in the absence of
      multicellularity in the siphonous algae, which are single cells. Morphogenesis is
      separate from cellular division in the land plants, which although are
      multicellular, have been argued to exhibit properties similar to single celled
      organisms. Within the single, macroscopic cell of a siphonous alga, how are
      transcripts partitioned, and what can this tell us about the development of
      similar convergent structures in land plants? Here, we present a de novo
      assembled, intracellular transcriptomic atlas for the giant coenocyte Caulerpa
      taxifolia. Transcripts show a global, basal-apical pattern of distribution from
      the holdfast to the frond apex in which transcript identities roughly follow the
      flow of genetic information in the cell, transcription-to-translation. The
      analysis of the intersection of transcriptomic atlases of a land plant and
      Caulerpa suggests the recurrent recruitment of transcript accumulation patterns
      to organs over large evolutionary distances. Our results not only provide an
      intracellular atlas of transcript localization, but also demonstrate the
      contribution of transcript partitioning to morphology, independent from
      multicellularity, in plants. 

PMID- 25569329
TI  - Potential environmental factors that influence the nitrogen concentration and
      delta(15)N values in the moss Hypnum cupressiforme collected inside and outside
      canopy drip lines.
AB  - Samples of the moss Hypnum cupressiforme were collected at 103 locations in
      forests of Slovenia. At each location, samples were taken at two types of sites:
      under tree canopies and in adjacent forest openings. The results show that the
      moss collected in the forest openings reflects the surrounding land-use
      characteristics and, consequently, the main N emission sources. For moss sampled
      under canopies, the characteristics of the forest at the moss-sampling locations
      are more important than the main emission sources outside the forest. A
      regression model was used to provide the nitrogen (N) concentration in moss from
      the forest openings in relation to the N concentration in moss under canopies and
      other environmental variables. The spatial distribution of the locations of the N
      concentrations and delta(15)N values in moss collected in the forest openings and
      under the canopies in relation to main N deposition sources is discussed. 

PMID- 25569330
TI  - Vibrational spectroscopic image analysis of biological material using
      multivariate curve resolution-alternating least squares (MCR-ALS).
AB  - Raman and Fourier transform IR (FTIR) microspectroscopic images of biological
      material (tissue sections) contain detailed information about their chemical
      composition. The challenge lies in identifying changes in chemical composition,
      as well as locating and assigning these changes to different conditions
      (pathology, anatomy, environmental or genetic factors). Multivariate data
      analysis techniques are ideal for decrypting such information from the data. This
      protocol provides a user-friendly pipeline and graphical user interface (GUI) for
      data pre-processing and unmixing of pixel spectra into their contributing pure
      components by multivariate curve resolution-alternating least squares (MCR-ALS)
      analysis. The analysis considers the full spectral profile in order to identify
      the chemical compounds and to visualize their distribution across the sample to
      categorize chemically distinct areas. Results are rapidly achieved (usually <30
      60 min per image), and they are easy to interpret and evaluate both in terms of
      chemistry and biology, making the method generally more powerful than principal
      component analysis (PCA) or heat maps of single-band intensities. In addition,
      chemical and biological evaluation of the results by means of reference matching
      and segmentation maps (based on k-means clustering) is possible. 

PMID- 25569331
TI  - Synthesis and use of an asymmetric transfer hydrogenation catalyst based on
      iron(II) for the synthesis of enantioenriched alcohols and amines.
AB  - The catalytic hydrogenation of prochiral ketones and imines is an advantageous
      approach to the synthesis of enantioenriched alcohols and amines, respectively,
      which are two classes of compounds that are highly prized in pharmaceutical,
      fragrance and flavoring chemistry. This hydrogenation reaction is generally
      carried out using ruthenium-based catalysts. Our group has developed an
      alternative synthetic route that is based on the environmentally friendlier iron
      based catalysis. This protocol describes the three-part synthesis of trans
      [amine(imine)diphosphine]chlorocarbonyliron(II) tetrafluoroborate templated by
      iron salts and starting from commercially available chemicals, which provides the
      precatalyst for the efficient asymmetric transfer hydrogenation of ketones and
      imines. The use of the enantiopure (S,S) catalyst to reduce prochiral ketones to
      the (R)-alcohol in good to excellent yields and enantioenrichment is also
      detailed, as well as the reduction to the amine in very high yield and
      enantiopurity of imines substituted at the nitrogen with the N
      (diphenylphosphinoyl) group (-P(O)Ph2). Although the best ruthenium catalysts
      provide alcohols in higher enantiomeric excess (ee) than the iron complex
      catalyst used in this protocol, they do so on much longer time scales or at
      higher catalyst loadings. This protocol can be completed in 2 weeks. 

PMID- 25569333
TI  - Suitability of polystyrene as a functional barrier layer in coloured food contact
      materials.
AB  - Functional barriers in food contact materials (FCMs) are used to prevent or
      reduce migration from inner layers in multilayer structures to food. The
      effectiveness of functional barrier layers was investigated in coloured
      polystyrene (PS) bowls due to their intended condition of use with hot liquids
      such as soups or stew. Migration experiments were performed over a 10-day period
      using USFDA-recommended food simulants (10% ethanol, 50% ethanol, corn oil and
      Miglyol) along with several other food oils. At the end of the 10 days, solvent
      dyes had migrated from the PS bowls at 12, 1 and 31,000 ng cm(-)(2) into coconut
      oil, palm kernel oil and Miglyol respectively, and in coconut oil and Miglyol the
      colour change was visible to the human eye. Scanning electron microscope (SEM)
      images revealed that the functional barrier was no longer intact for the bowls
      exposed to coconut oil, palm kernel oil, Miglyol, 10% ethanol, 50% ethanol and
      goat's milk. Additional tests showed that 1-dodecanol, a lauryl alcohol derived
      from palm kernel oil and coconut oil, was present in the PS bowls at an average
      concentration of 11 mg kg(-1). This compound is likely to have been used as a
      dispersing agent for the solvent dye and aided the migration of the solvent dye
      from the PS bowl into the food simulant. The solvent dye was not found in the 10%
      ethanol, 50% ethanol and goat's milk food simulants above their respective limits
      of detection, which is likely to be due to its insolubility in aqueous solutions.
      A disrupted barrier layer is of concern because if there are unregulated
      materials in the inner layers of the laminate, they may migrate to food, and
      therefore be considered unapproved food additives resulting in the food being
      deemed adulterated under the Federal Food Drug and Cosmetic Act.

PMID- 25569334
TI  - Quantitative analysis in capillary electrophoresis: transformation of raw
      electropherograms into continuous distributions.
AB  - Quantitative analysis in capillary electrophoresis based on time-scale
      electropherograms generally uses time-corrected peak areas to account for the
      differences in apparent velocities between solutes. However, it could be
      convenient and much more relevant to change the time-scale electropherograms into
      mass relative distribution of the effective mobility or any other characteristic
      parameter (molar mass, chemical composition, charge density, ...). In this study,
      the theoretical background required to perform the variable change on the
      electropherogram was developed with an emphasis on the fact that both x and y
      axes should be changed when the time scale electropherograms are modified to get
      the distributions. Applications to the characterization of polymers and
      copolymers by different modes of capillary electrophoresis (CE) are presented,
      including the molar mass distribution of poly-L-lysine oligomers by capillary gel
      electrophoresis (CGE), molar mass distribution of end-charged poly-l-alanine by
      free solution CE, molar mass distribution of evenly charged polyelectrolytes by
      CGE, and charge density distribution of variously charged polyelectrolytes by
      free solution CE.

PMID- 25569332
TI  - Imaging liver biology in vivo using conventional confocal microscopy.
AB  - Imaging of live animals using intravital microscopy (IVM) has provided a
      substantial advance in our understanding of cell biology. Here we describe how to
      adapt a conventional, relatively low-cost laser-scanning microscope to operate as
      a versatile imaging station. We present the surgical procedures needed to perform
      liver confocal IVM in mice, thereby allowing one to image different cells in
      their native environment, including hepatocytes, endothelial cells and
      leukocytes, as well as to analyze their morphology and function under
      physiological or pathological conditions. In addition, we propose a plethora of
      working doses of antibodies and probes to stain multiple cells and molecules
      simultaneously in vivo. Considering the central role of the liver in metabolism
      and immunity and the growing interest in the relationship between immune and
      parenchymal cells, this protocol, in which 20 min of preparation yields up to 4 h
      of imaging, provides useful insights for various research fields. In addition,
      the protocol can be easily adapted to investigate adipose tissue, mesentery,
      intestines, spleen and virtually any abdominal organ. 

PMID- 25569336
TI  - Intravenous fluid therapy in adult inpatients.

PMID- 25569335
TI  - What makes a protein sequence a prion?
AB  - Typical amyloid diseases such as Alzheimer's and Parkinson's were thought to
      exclusively result from de novo aggregation, but recently it was shown that
      amyloids formed in one cell can cross-seed aggregation in other cells, following
      a prion-like mechanism. Despite the large experimental effort devoted to
      understanding the phenomenon of prion transmissibility, it is still poorly
      understood how this property is encoded in the primary sequence. In many cases,
      prion structural conversion is driven by the presence of relatively large
      glutamine/asparagine (Q/N) enriched segments. Several studies suggest that it is
      the amino acid composition of these regions rather than their specific sequence
      that accounts for their priogenicity. However, our analysis indicates that it is
      instead the presence and potency of specific short amyloid-prone sequences that
      occur within intrinsically disordered Q/N-rich regions that determine their prion
      behaviour, modulated by the structural and compositional context. This provides a
      basis for the accurate identification and evaluation of prion candidate sequences
      in proteomes in the context of a unified framework for amyloid formation and
      prion propagation. 

PMID- 25569337
TI  - Development and application of a quantitative multiplexed small GTPase activity
      assay using targeted proteomics.
AB  - Small GTPases are a family of key signaling molecules that are ubiquitously
      expressed in various types of cells. Their activity is often analyzed by western
      blot, which is limited by its multiplexing capability, the quality of isoform
      specific antibodies, and the accuracy of quantification. To overcome these
      issues, a quantitative multiplexed small GTPase activity assay has been
      developed. Using four different binding domains, this assay allows the binding of
      up to 12 active small GTPase isoforms simultaneously in a single experiment. To
      accurately quantify the closely related small GTPase isoforms, a targeted
      proteomic approach, i.e., selected/multiple reaction monitoring, was developed,
      and its functionality and reproducibility were validated. This assay was
      successfully applied to human platelets and revealed time-resolved coactivation
      of multiple small GTPase isoforms in response to agonists and differential
      activation of these isoforms in response to inhibitor treatment. This widely
      applicable approach can be used for signaling pathway studies and inhibitor
      screening in many cellular systems. 

PMID- 25569338
TI  - Intranasal vaccination with leishmanial antigens protects golden hamsters
      (Mesocricetus auratus) against Leishmania (Viannia) Braziliensis infection.
AB  - BACKGROUND: Previous results have shown that oral and intranasal administration
      of particulate Leishmania (Leishmania) amazonensis antigens (LaAg) partially
      protects mice against L. amazonensis infection. However, vaccination studies on
      species of the subgenus Viannia, the main causative agent of cutaneous and
      mucosal leishmaniasis in the Americas, have been hampered by the lack of easy-to
      handle bio-models that accurately mimic the human disease. Recently, we
      demonstrated that the golden hamster is an appropriate model for studying the
      immunopathogenesis of cutaneous leishmaniasis caused by L. (Viannia)
      braziliensis. Using the golden hamster model, our current study investigated
      whether the protective effect of intranasal immunisation with LaAg can be
      extended to L. braziliensis infection. METHODOLOGY/PRINCIPAL FINDINGS: Golden
      hamsters vaccinated with either two intranasal (IN) doses of LaAg (10 ug) or two
      intramuscular doses of LaAg (20 ug) were challenged 2 weeks post-vaccination with
      L. braziliensis. The results showed that IN immunisation with LaAg significantly
      reduced lesion growth and parasitic load as well as serum IgG and IgG2 levels. At
      the experimental endpoint on day 114 post-infection, IN-immunised hamsters that
      were considered protected expressed IFN-gamma and IL10 mRNA levels that returned
      to uninfected skin levels. In contrast to the nasal route, intramuscular (IM)
      immunisation failed to provide protection. CONCLUSIONS/SIGNIFICANCE: These
      results demonstrate for the first time that the nasal route of immunisation can
      induce cross protection against L. braziliensis infection.

PMID- 25569340
TI  - Reduction of assaultive behavior following anger treatment of forensic hospital
      patients with intellectual disabilities.
AB  - Anger is related to violence prior to hospitalization, during hospitalization,
      and after discharge. Meta-analyses have established treatment efficacy in
      reducing anger, but few studies have addressed whether reduced anger leads to
      lowered aggressive behavior. This study concerns individually-delivered anger
      treatment, specialized for offenders with intellectual disabilities, delivered
      twice weekly for 18 sessions to 50 forensic hospital patients. Assessments
      involved patient self-report of anger, staff ratings of anger and aggression, and
      case records of assaultive incidents. Physical assault data were obtained from
      records 12 months pre-treatment and 12 months post-treatment. Significant
      reductions in assaults following treatment were found by GEE analyses,
      controlling for age, gender, length of stay, IQ, and pre-hospital violence.
      Following treatment, physical attacks reduced by more than half, dropping from
      approximately 3.5 attacks per patient 6 months prior to treatment, versus
      approximately 1 attack per patient in the 6-12 month interval post-treatment. In
      hierarchical regressions, controlling for IQ, reduction in physical assaults was
      associated with pre-to post-treatment change in anger level. These findings
      buttress the efficacy of anger treatment for patients having histories of
      violence and have significance for patient mental health, hospital staff well
      being, therapeutic milieu, hospital management, and service delivery costs. 

PMID- 25569339
TI  - Imagery enhancements increase the effectiveness of cognitive behavioural group
      therapy for social anxiety disorder: a benchmarking study.
AB  - Emerging evidence suggests that imagery-based techniques may enhance the
      effectiveness of traditional verbal-linguistic cognitive interventions for
      emotional disorders. This study extends an earlier pilot study by reporting
      outcomes from a naturalistic trial of an imagery-enhanced cognitive behavioural
      group therapy (IE-CBGT, n = 53) protocol for social anxiety disorder (SAD), and
      comparing outcomes to historical controls who completed a predominantly verbally
      based group protocol (n = 129). Patients were consecutive referrals from health
      professionals to a community clinic specialising in anxiety and mood disorders.
      Both treatments involved 12, two-hour group sessions plus a one-month follow-up.
      Analyses evaluated treatment adherence, predictors of dropout, treatment effect
      sizes, reliable and clinically significant change, and whether self-reported
      tendencies to use imagery in everyday life and imagery ability predicted symptom
      change. IE-CBGT patients were substantially more likely to complete treatment
      than controls (91% vs. 65%). Effect sizes were very large for both treatments,
      but were significantly larger for IE-CBGT. A higher proportion of the IE-CBGT
      patients achieved reliable change, and better imagery ability was associated with
      larger symptom change. Outcomes compared very favourably to published group and
      individual treatments for SAD, suggesting that IE-CBGT may be a particularly
      effective and efficient mode of treatment delivery. 

PMID- 25569341
TI  - Linking the VPS35 and EIF4G1 pathways in Parkinson's disease.
AB  - Elucidating the underlying pathogenic pathways in Parkinson's disease will be
      critical for targeted drug development. In this issue of Neuron, Dhungel et al.
      (2015) utilize a yeast model to establish a link between VPS35 and EIF4G1 in
      alpha-synuclein-related neurodegeneration. 

PMID- 25569342
TI  - New neurons don't talk back.
AB  - GABAergic interneurons enforce highly sparse activity patterns in principal
      neurons of the dentate gyrus. In this issue of Neuron, Temprana et al. (2015)
      show that immature adult-born neurons largely function independently of
      inhibitory feedback circuits, neither receiving nor generating feedback
      inhibition.

PMID- 25569343
TI  - On the brink: a new synaptic vesicle release model at the calyx of held.
AB  - How vesicle calcium sensors interact with calcium channels at synapses affects
      neurotransmitter release dynamics. In this issue of Neuron, Nakamura et al.
      (2015) propose that synaptic vesicles are tightly coupled around the perimeter of
      a voltage-gated calcium channel cluster. 

PMID- 25569344
TI  - CA2: it's about time-and episodes.
AB  - In this issue of Neuron, Mankin et al. (2015) show that CA2, an oft-neglected
      hippocampal subregion, has place representations that change from one episode to
      the next, even as the spatial environment does not. This finding may help explain
      how time is encoded in episodic memories. 

PMID- 25569345
TI  - Prediction as a humanitarian and pragmatic contribution from human cognitive
      neuroscience.
AB  - Neuroimaging has greatly enhanced the cognitive neuroscience understanding of the
      human brain and its variation across individuals (neurodiversity) in both health
      and disease. Such progress has not yet, however, propelled changes in educational
      or medical practices that improve people's lives. We review neuroimaging findings
      in which initial brain measures (neuromarkers) are correlated with or predict
      future education, learning, and performance in children and adults; criminality;
      health-related behaviors; and responses to pharmacological or behavioral
      treatments. Neuromarkers often provide better predictions (neuroprognosis), alone
      or in combination with other measures, than traditional behavioral measures. With
      further advances in study designs and analyses, neuromarkers may offer
      opportunities to personalize educational and clinical practices that lead to
      better outcomes for people. 

PMID- 25569347
TI  - Cell lineage analysis in human brain using endogenous retroelements.
AB  - Somatic mutations occur during brain development and are increasingly implicated
      as a cause of neurogenetic disease. However, the patterns in which somatic
      mutations distribute in the human brain are unknown. We used high-coverage whole
      genome sequencing of single neurons from a normal individual to identify
      spontaneous somatic mutations as clonal marks to track cell lineages in human
      brain. Somatic mutation analyses in >30 locations throughout the nervous system
      identified multiple lineages and sublineages of cells marked by different LINE-1
      (L1) retrotransposition events and subsequent mutation of poly-A microsatellites
      within L1. One clone contained thousands of cells limited to the left middle
      frontal gyrus, whereas a second distinct clone contained millions of cells
      distributed over the entire left hemisphere. These patterns mirror known somatic
      mutation disorders of brain development and suggest that focally distributed
      mutations are also prevalent in normal brains. Single-cell analysis of somatic
      mutation enables tracing of cell lineage clones in human brain. 

PMID- 25569346
TI  - Genomic perspectives of transcriptional regulation in forebrain development.
AB  - The forebrain is the seat of higher-order brain functions, and many human
      neuropsychiatric disorders are due to genetic defects affecting forebrain
      development, making it imperative to understand the underlying genetic circuitry.
      Recent progress now makes it possible to begin fully elucidating the genomic
      regulatory mechanisms that control forebrain gene expression. Herein, we discuss
      the current knowledge of how transcription factors drive gene expression programs
      through their interactions with cis-acting genomic elements, such as enhancers;
      how analyses of chromatin and DNA modifications provide insights into gene
      expression states; and how these approaches yield insights into the evolution of
      the human brain. 

PMID- 25569348
TI  - Protein arginine methyltransferase 6 enhances polyglutamine-expanded androgen
      receptor function and toxicity in spinal and bulbar muscular atrophy.
AB  - Polyglutamine expansion in androgen receptor (AR) is responsible for spinobulbar
      muscular atrophy (SBMA) that leads to selective loss of lower motor neurons.
      Using SBMA as a model, we explored the relationship between protein
      structure/function and neurodegeneration in polyglutamine diseases. We show here
      that protein arginine methyltransferase 6 (PRMT6) is a specific co-activator of
      normal and mutant AR and that the interaction of PRMT6 with AR is significantly
      enhanced in the AR mutant. AR and PRMT6 interaction occurs through the PRMT6
      steroid receptor interaction motif, LXXLL, and the AR activating function 2
      surface. AR transactivation requires PRMT6 catalytic activity and involves
      methylation of arginine residues at Akt consensus site motifs, which is mutually
      exclusive with serine phosphorylation by Akt. The enhanced interaction of PRMT6
      and mutant AR leads to neurodegeneration in cell and fly models of SBMA. These
      findings demonstrate a direct role of arginine methylation in polyglutamine
      disease pathogenesis. 

PMID- 25569350
TI  - Hippocampal CA2 activity patterns change over time to a larger extent than
      between spatial contexts.
AB  - The hippocampal CA2 subregion has a different anatomical connectivity pattern
      within the entorhino-hippocampal circuit than either the CA1 or CA3 subregion.
      Yet major differences in the neuronal activity patterns of CA2 compared with the
      other CA subregions have not been reported. We show that standard spatial and
      temporal firing patterns of individual hippocampal principal neurons in behaving
      rats, such as place fields, theta modulation, and phase precession, are also
      present in CA2, but that the CA2 subregion differs substantially from the other
      CA subregions in its population coding. CA2 ensembles do not show a persistent
      code for space or for differences in context. Rather, CA2 activity patterns
      become progressively dissimilar over time periods of hours to days. The weak
      coding for a particular context is consistent with recent behavioral evidence
      that CA2 circuits preferentially support social, emotional, and temporal rather
      than spatial aspects of memory. 

PMID- 25569349
TI  - Rapid dispersion of SynGAP from synaptic spines triggers AMPA receptor insertion
      and spine enlargement during LTP.
AB  - SynGAP is a Ras-GTPase activating protein highly enriched at excitatory synapses
      in the brain. Previous studies have shown that CaMKII and the RAS-ERK pathway are
      critical for several forms of synaptic plasticity including LTP. NMDA receptor
      dependent calcium influx has been shown to regulate the RAS-ERK pathway and
      downstream events that result in AMPA receptor synaptic accumulation, spine
      enlargement, and synaptic strengthening during LTP. However, the cellular
      mechanisms whereby calcium influx and CaMKII control Ras activity remain elusive.
      Using live-imaging techniques, we have found that SynGAP is rapidly dispersed
      from spines upon LTP induction in hippocampal neurons, and this dispersion
      depends on phosphorylation of SynGAP by CaMKII. Moreover, the degree of acute
      dispersion predicts the maintenance of spine enlargement. Thus, the synaptic
      dispersion of SynGAP by CaMKII phosphorylation during LTP represents a key
      signaling component that transduces CaMKII activity to small G protein-mediated
      spine enlargement, AMPA receptor synaptic incorporation, and synaptic
      potentiation. 

PMID- 25569351
TI  - Functionally defined white matter reveals segregated pathways in human ventral
      temporal cortex associated with category-specific processing.
AB  - It is unknown if the white-matter properties associated with specific visual
      networks selectively affect category-specific processing. In a novel protocol we
      combined measurements of white-matter structure, functional selectivity, and
      behavior in the same subjects. We find two parallel white-matter pathways along
      the ventral temporal lobe connecting to either face-selective or place-selective
      regions. Diffusion properties of portions of these tracts adjacent to face- and
      place-selective regions of ventral temporal cortex correlate with behavioral
      performance for face or place processing, respectively. Strikingly, adults with
      developmental prosopagnosia (face blindness) express an atypical structure
      behavior relationship near face-selective cortex, suggesting that white-matter
      atypicalities in this region may have behavioral consequences. These data suggest
      that examining the interplay between cortical function, anatomical connectivity,
      and visual behavior is integral to understanding functional networks and their
      role in producing visual abilities and deficits.

PMID- 25569353
TI  - Endocrine disrupting chemicals in the atmosphere: Their effects on humans and
      wildlife.
AB  - Endocrine disrupting chemicals (EDCs) are exogenous agents that interfere or
      disrupt the normal synthesis, secretion, transportation, binding and metabolism
      of natural hormones; eventually dysregulating homeostatic mechanisms,
      reproduction and development. They are emitted into the atmosphere during
      anthropogenic activities and physicochemical reactions in nature. Inhalation of
      these EDCs as particulate and gaseous vapors triggers their interaction with
      endocrine glands and exerts agonist or antagonists actions at hormone receptors.
      The endocrine disruption at nanogram levels of EDC's has gained concern in the
      last decade, due to infertility among men and women, early puberty, obesity,
      diabetes and cancer. Thus, the review explores the literature that addresses the
      major occurring EDCs in the atmosphere including phthalates, polychlorinated
      biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), brominated flame
      retardants (BFRs), dioxins, alkylphenols (APs) and perfluorinated chemicals
      (PFCs). Sources, fate, half-life, mechanism, measured concentrations in air,
      bioaccumulation in tissues, laboratory exposures correlating to toxicological
      effects of these EDCs in humans and wildlife are discussed. 

PMID- 25569352
TI  - Rh-Catalyzed decarbonylative coupling with alkynes via C-C activation of isatins.
AB  - Herein we report a [5 + 2 - 1] transformation though catalytic decarbonylative
      coupling between isatins and alkynes, which provides a unique way to synthesize 2
      quinolinone derivatives. A broad range of alkynes can be coupled efficiently with
      high regioselectivity. This reaction is proposed to go through C-C activation of
      isatins, followed by decarbonylation and alkyne insertion. Directing group (DG)
      plays a critical role in this transformation. Assisted by the DG, the C-C
      cleavage of isatins occurs at room temperature. 

PMID- 25569354
TI  - Effects of active versus passive recovery in sprint cross-country skiing.
AB  - PURPOSE: To investigate the effects of an active and a passive recovery protocol
      on physiological responses and performance between 2 heats in sprint cross
      country skiing. METHODS: Ten elite male skiers (22+/-3 y, 184+/-4 cm, 79+/-7 kg)
      undertook 2 experimental test sessions that both consisted of 2 heats with 25 min
      between start of the first and second heats. The heats were conducted as an 800-m
      time trial (6 degrees , >3.5 m/s, ~205 s) and included measurements of oxygen
      uptake (VO2) and accumulated oxygen deficit. The active recovery trial involved 2
      min standing/walking, 16 min jogging (58%+/-5% of VO2peak), and 3 min
      standing/walking. The passive recovery trial involved 15 min sitting, 3 min
      walk/jog (~30% of VO2peak), and 3 min standing/walking. Blood lactate
      concentration and heart rate were monitored throughout the recovery periods.
      RESULTS: The increased 800-m time between heat 1 and heat 2 was trivial after
      active recovery (effect size [ES]=0.1, P=.64) and small after passive recovery
      (ES=0.4, P=.14). The 1.2%+/-2.1% (mean+/-90% CL) difference between protocols was
      not significant (ES=0.3, P=.3). In heat 2, peak and average VO2 was increased
      after the active recovery protocol. CONCLUSIONS: Neither passive recovery nor
      running at ~58% of VO2peak between 2 heats changed performance significantly.

PMID- 25569356
TI  - Lung CD200 Receptor Activation Abrogates Airway Hyperresponsiveness in
      Experimental Asthma.
AB  - In allergic asthma, homeostatic pathways are dysregulated, which leads to an
      immune response toward normally innocuous antigens. The CD200-CD200 receptor
      pathway is a central regulator of inflammation, and CD200 expression was recently
      found to be down-regulated in circulating leukocytes of patients with asthma.
      Given the antiinflammatory properties of CD200, we investigated whether local
      delivery of recombinant CD200 (rCD200) could reinstate lung homeostasis in an
      experimental model of asthma. Brown Norway rats were sensitized with ovalbumin
      (OVA) and alum. rCD200 was intratracheally administered 24 hours before OVA
      challenge, and airway responsiveness to methacholine was measured 24 hours after
      the allergen challenge. Inflammation was also assessed by measuring cell
      recruitment and cytokine levels in bronchoalveolar lavages, as well as lung and
      draining lymph node accumulation of dendritic cells (DCs) and T cells. In
      sensitized rats, rCD200 abolished airway hyperresponsiveness, whereas the sham
      treatment had no effect. In addition, rCD200 strongly reduced OVA-induced lung
      accumulation of myeloid DCs, CD4(+) T cells, and T helper type 2 cells. This was
      associated with a strong reduction of OVA-induced IL-13 level and with an
      increase of IL-10 in supernatants of bronchoalveolar lavages. Lung eosinophilia
      and draining lymph node accumulation of myeloid DCs and T cells were not affected
      by rCD200. Overall, these data reveal that rCD200 can inhibit airway
      hyperresponsiveness in a model of asthma by a multistep mechanism associated with
      local alterations of the T cell response and the cytokine milieu. 

PMID- 25569355
TI  - A re-examination of the selection of the sensory organ precursor of the bristle
      sensilla of Drosophila melanogaster.
AB  - The bristle sensillum of the imago of Drosophila is made of four cells that arise
      from a sensory organ precursor cell (SOP). This SOP is selected within proneural
      clusters (PNC) through a mechanism that involves Notch signalling. PNCs are
      defined through the expression domains of the proneural genes, whose activities
      enables cells to become SOPs. They encode tissue specific bHLH proteins that form
      functional heterodimers with the bHLH protein Daughterless (Da). In the
      prevailing lateral inhibition model for SOP selection, a transcriptional feedback
      loop that involves the Notch pathway amplifies small differences of proneural
      activity between cells of the PNC. As a result only one or two cells accumulate
      sufficient proneural activity to adopt the SOP fate. Most of the experiments that
      sustained the prevailing lateral inhibition model were performed a decade ago. We
      here re-examined the selection process using recently available reagents. Our
      data suggest a different picture of SOP selection. They indicate that a band-like
      region of proneural activity exists. In this proneural band the activity of the
      Notch pathway is required in combination with Emc to define the PNCs. We found a
      sub-group in the PNCs from which a pre-selected SOP arises. Our data indicate
      that most imaginal disc cells are able to adopt a proneural state from which they
      can progress to become SOPs. They further show that bristle formation can occur
      in the absence of the proneural genes if the function of emc is abolished. These
      results suggest that the tissue specific proneural proteins of Drosophila have a
      similar function as in the vertebrates, which is to determine the time of
      emergence and position of the SOP and to stabilise the proneural state. 

PMID- 25569357
TI  - Developmental regulation of the Tetrahymena thermophila origin recognition
      complex.
AB  - The Tetrahymena thermophila DNA replication machinery faces unique demands due to
      the compartmentalization of two functionally distinct nuclei within a single
      cytoplasm, and complex developmental program. Here we present evidence for
      programmed changes in ORC and MCM abundance that are not consistent with
      conventional models for DNA replication. As a starting point, we show that ORC
      dosage is critical during the vegetative cell cycle and development. A moderate
      reduction in Orc1p induces genome instability in the diploid micronucleus,
      aberrant division of the polyploid macronucleus, and failure to generate a robust
      intra-S phase checkpoint response. In contrast to yeast ORC2 mutants, replication
      initiation is unaffected; instead, replication forks elongation is perturbed, as
      Mcm6p levels decline in parallel with Orc1p. Experimentally induced down
      regulation of ORC and MCMs also impairs endoreplication and gene amplification,
      consistent with essential roles during development. Unexpectedly Orc1p and Mcm6p
      levels fluctuate dramatically in developing wild type conjugants, increasing for
      early cycles of conventional micronuclear DNA replication and macronuclear
      anlagen replication (endoreplication phase I, rDNA gene amplification). This
      increase does not reflect the DNA replication load, as much less DNA is
      synthesized during this developmental window compared to vegetative S phase.
      Furthermore, although Orc1p levels transiently increase prior to endoreplication
      phase II, Orc1p and Mcm6p levels decline when the replication load increases and
      unconventional DNA replication intermediates are produced. We propose that
      replication initiation is re-programmed to meet different requirements or
      challenges during the successive stages of Tetrahymena development. 

PMID- 25569359
TI  - Visualizing cellular imaging data using PhenoPlot.
AB  - Visualization is essential for data interpretation, hypothesis formulation and
      communication of results. However, there is a paucity of visualization methods
      for image-derived data sets generated by high-content analysis in which complex
      cellular phenotypes are described as high-dimensional vectors of features. Here
      we present a visualization tool, PhenoPlot, which represents quantitative high
      content imaging data as easily interpretable glyphs, and we illustrate how
      PhenoPlot can be used to improve the exploration and interpretation of complex
      breast cancer cell phenotypes. 

PMID- 25569358
TI  - Preferential targeting of disseminated liver tumors using a recombinant adeno
      associated viral vector.
AB  - A novel selectively targeting gene delivery approach has been developed for
      advanced hepatocellular carcinoma (HCC), a leading cause of cancer mortality
      whose prognosis remains poor. We combine the strong liver tropism of serotype-8
      capsid-pseudotyped adeno-associated viral vectors (AAV8) with a liver-specific
      promoter (HLP) and microRNA-122a (miR-122a)-mediated posttranscriptional
      regulation. Systemic administration of our AAV8 construct resulted in
      preferential transduction of the liver and encouragingly of HCC at heterotopic
      sites, a finding that could be exploited to target disseminated disease. Tumor
      selectivity was enhanced by inclusion of miR-122a-binding sequences (ssAAV8-HLP
      TK-122aT4) in the expression cassette, resulting in abrogation of transgene
      expression in normal murine liver but not in HCC. Systemic administration of our
      tumor-selective vector encoding herpes simplex virus-thymidine kinase (TK)
      suicide gene resulted in a sevenfold reduction in HCC growth in a syngeneic
      murine model without toxicity. In summary, we have developed a systemically
      deliverable gene transfer approach that enables high-level expression of
      therapeutic genes in HCC but not normal tissues, thus improving the prospects of
      safe and effective treatment for advanced HCC. 

PMID- 25569360
TI  - Characteristics of PVDF Membranes Irradiated by Electron Beam.
AB  - Polyvinylidene fluoride (PVDF) membranes were exposed vertically to a high energy
      electron beam (EB) in air, at room temperature. The chemical changes were
      examined by Fourier Transform Infrared Spectroscopy (FTIR). The surface
      morphologies were studied by Scanning Electron Microscopy (SEM) and showed some
      changes in the pore size. Thermogravimetric (TGA) analysis represented an
      increase in the thermal stability of PVDF due to irradiation. Electron
      paramagnetic resonance (EPR) showed the presence of free radicals in the
      irradiated PVDF. The effect of EB irradiation on the electrical properties of the
      membranes was analyzed in order to determine the dielectric constant, and an
      increase in the dielectric constant was found on increasing the dose. The surface
      hydrophilicity of the modified membrane was characterized by water contact angle
      measurement. The contact angle decreased compared to the original angle,
      indicating an improvement of surface hydrophilicity. Filtration results also
      showed that the pure water flux (PWF) of the modified membrane was lower than
      that of the unirradiated membrane. 

PMID- 25569362
TI  - Hyperventilation-induced nystagmus in patients with vestibular schwannoma.
AB  - MAIN OBJECTIVE: To determine the utility of the hyperventilation test (HVT) in
      the diagnosis of vestibular schwannoma (VS). STUDY DESIGN: A retrospective
      analysis of hyperventilation-induced nystagmus (HVIN) in 45 patients with
      unilateral VS. SETTING: A tertiary referral center. PATIENTS: Forty-five patients
      with VS; 30 patients with chronic vestibular neuritis; 20 healthy subjects with
      normal hearing and without symptoms or a history of vertigo, migraine, or
      neurological diseases (control group). INTERVENTIONS: Audiological and vestibular
      examination; "side-stream" measurement of end-tidal CO2 pressure (P(EtCO2)) to
      standardize the procedure; magnetic resonance imaging (MRI) centered on the
      cerebellopontine angle. MAIN OUTCOME MEASURES: An analysis of HVIN, its patterns,
      and its appearance threshold via the measurement of P(EtCO2) correlations with
      the tumor size. RESULTS: HVIN was observed in 40 of 45 cases (88.9%) in the
      schwannoma group and in 12 of 30 cases (40%) in the chronic vestibular neuritis
      group; HVIN was not observed in the control group (0/20 cases) (p < 0.001). In
      the schwannoma group, HVIN was evoked at a mean P(EtCO2) value of 16.5 +/- 1.15
      mm Hg. The hypofunctional labyrinth was identified with high sensibility and
      specificity through caloric test, head shaking test, and head thrust test. The
      excitatory pattern, which included HVIN with slow phases that beat toward the
      hypofunctional side, and the paretic pattern, which included HVIN with slow
      phases that beat toward the hypofunctional side, were not significantly
      associated with VS size (19.04 +/- 10.56 mm for the excitatory pattern and 19.06
      +/- 11.01 mm for the paretic pattern). The difference in the VS size in HVIN+
      (19.05 +/- 10.60 mm) and HVIN- (8.40 +/- 2.19 mm) cases was significant (p =
      0.009). CONCLUSIONS: A 60-second hyperventilation event causes metabolic changes
      in the vestibular system and reveals a latent vestibular asymmetry. The presence
      of an excitatory pattern is the major criterion that suggests VS in patients with
      signs of unilateral vestibular deficit.

PMID- 25569361
TI  - Identification of target proteins involved in cochlear otosclerosis.
AB  - HYPOTHESIS: Investigation of differential protein expression will provide clues
      to pathophysiology in otosclerosis. BACKGROUND: Otosclerosis is a bone remodeling
      disorder limited to the endochondral layer of the otic capsule within the
      temporal bone. Some authors have suggested an inflammatory etiology for
      otosclerosis resulting from persistent measles virus infection involving the otic
      capsule. Despite numerous genetic studies, implication of candidate genes in the
      otosclerotic process remains elusive. We employed liquid chromatography-mass
      spectrometry (LC-MS) analysis on formalin-fixed celloidin-embedded temporal bone
      tissues for postmortem investigation of otosclerosis. METHODS: Proteomic analysis
      was performed using human temporal bones from a patient with severe otosclerosis
      and a control temporal bone. Sections were dissected under microscopy to remove
      otosclerotic lesions and normal otic capsule for proteomic analysis. Tandem 2D
      chromatography mass spectrometry was employed. Data analysis and peptide matching
      to FASTA human databases was done using SEQUEST and proteome discoverer software.
      RESULTS: TGFbeta1 was identified in otosclerosis but not in the normal control
      temporal bone specimen. Aside from TGFbeta1, many proteins and predicted cDNA
      encoded proteins were observed, with implications in cell death and/or
      proliferation pathways, suggesting a possible role in otosclerotic bone
      remodeling. Immunostaining using TGFbeta1 monoclonal revealed marked staining of
      the spongiotic otosclerotic lesions. CONCLUSIONS: Mechanisms involved in cochlear
      extension of otosclerosis are still unclear, but the implication of TGFbeta1 is
      supported by the present proteomic data and immunostaining results. The
      established role of TGFbeta1 in the chondrogenesis process supports the theory of
      a reaction targeting the globulae interossei within the otic capsule.

PMID- 25569363
TI  - Evaluation of Bone Conduction Implant Stability and Soft Tissue Status in
      Children in Relation to Age, Bone Thickness, and Sound Processor Loading Time.
AB  - OBJECTIVE: To measure the stability, as determined by implant stability quotient
      (ISQ) values, of bone conduction implants placed using FAST (one-stage) surgery
      in children to look for the differences between various ages and indications. To
      monitor the status of the peri-implant soft tissue using the classification
      proposed by Holgers et al. STUDY DESIGN: It was a prospective, open, multicenter
      study performed in two investigation centers. PATIENTS: Twenty-two subjects under
      18 years of age implanted with the Cochlear BIA300 and BIA400 types of devices at
      the ENT Departments of Children's Hospitals in Bydgoszcz and Lodz in Poland.
      INTERVENTION(S): Implantation and use of the bone conduction implant system. The
      implants were placed unilaterally or bilaterally according to a one-stage
      surgical procedure as per normal practice at the hospitals. Loading time was
      adjusted to individual patient, and it was based on the assessment of implant
      stability and status of the soft tissue. MAIN OUTCOME MEASURE(S): The attention
      was given to the differences in the ISQ values obtained during the subsequent
      visits in the various age and indication groups. Resonance frequency analysis was
      performed as per the routine follow-up schedule at the hospital. RESULTS: Age at
      the time of implantation on average was 9.8 years (min. 5.2 yr; max. 16 yr). On
      average, ISQ value on each of the study observations in this group equaled to
      59.17 (median, 58.79). Seventh to tenth day post-surgery seemed to be a sensitive
      period as the lowest ISQ values (on average: 56.38 ISQ) were recorded for these
      dates. On average, implant was loaded 7.5 weeks after surgery in the study group
      (min. 2 wk, max. 14 wk). In none of the subjects the significant decrease of the
      implant stability values after sound processor loading was observed.
      Statistically significant correlation rate (p < 0.05) showed that the thicker the
      bone the higher the obtained ISQ value on each of the visits. It was also
      confirmed that the younger the implanted child, the higher the skin reactions
      grade at the 2 to 4 weeks post-sound processor fitting. There was no correlation
      observed between the time of the sound processor fitting and the skin reactions
      status.

PMID- 25569364
TI  - Preserved low-frequency hearing following 20-mm cochlear implantation.
AB  - OBJECTIVE: To determine the preservation of pure tone thresholds for a series of
      cochlear implant patients who underwent atraumatic round window insertion with a
      new thin 22-mm electrode to a 20-mm depth. STUDY DESIGN: Retrospective, within
      subject repeated measures design. SETTING: Tertiary care hospital. PATIENTS: Nine
      sequential cochlear implant patients with functional preoperative acoustic
      hearing (defined as low-frequency pure tone average thresholds <=90 dB).
      INTERVENTION: Therapeutic. MAIN OUTCOME MEASURE: Pure tone thresholds after
      cochlear implantation. RESULTS: Low-frequency hearing preservation was achieved
      in all cases. Less than 10 dB average change was seen for low-frequency pure tone
      average measures (125, 250, 500, and 1,000 Hz) at 6 and 12 months following
      cochlear implantation. CONCLUSIONS: Atraumatic round window insertion with a thin
      22-mm electrode to a 20-mm depth results in dramatically high levels of acoustic
      hearing preservation among CI patients.

PMID- 25569365
TI  - Outcomes of cochlear implantation in adults with asymmetric hearing loss.
AB  - OBJECTIVE: To analyze speech recognition outcomes in adult cochlear implant
      recipients who have asymmetric sensorineural hearing loss between the two ears.
      STUDY DESIGN: Retrospective cohort study of 35 adults with asymmetric hearing
      loss. Preoperative unaided pure-tone averages (PTA), and pre- and post-op (6 and
      12 mo) aided Consonant Nucleus Consonant (CNC) words and sentence recognition
      scores were obtained for ears in isolation (opposite ear plugged). Patients were
      categorized according to the PTA of the implanted and contralateral ears as (a)
      moderate-severe, (b) moderate-profound, and (c) severe-profound. SETTING: A
      single tertiary care center. PATIENTS: Adults with asymmetric PTA implanted
      unilaterally at our institution. INTERVENTION: Cochlear implantation with devices
      approved by the U.S. Food and Drug Administration. MAIN OUTCOME MEASURE(S): Post
      implantation word, phoneme, and sentence recognition in the cochlear implant
      alone testing condition. RESULTS: Patients who were implanted in the worse
      hearing ear (n = 21) performed significantly better on CNC words and phonemes at
      6 and 12 months than patients who were implanted in the better-hearing ear (n =
      14). Patients with the worse ear implanted also obtained 6 to 12% higher sentence
      recognition scores than the group received an implant in their better ear,
      although this difference is not statistically significant (p = 0.06 at 6 mo; p =
      0.1 at 12 mo). CONCLUSION: Patients with asymmetrical hearing loss who were
      implanted in the worse-hearing ear achieved 15% greater CNC word scores and 6 to
      12% greater sentence scores than patients implanted in the better-hearing ear in
      the first year after surgery. Our results provide further support for clinicians
      to use caution if considering implanting the better-hearing ear in patients with
      asymmetric hearing loss.

PMID- 25569366
TI  - Does electrocautery damage cochlear implants?
AB  - OBJECTIVES: 1) Evaluate the effects of monopolar cautery on cochlear implant
      devices. 2) Determine whether voltage fluctuations within the cochlear implant
      adversely affect the cochlear implant devices STUDY DESIGN: Two Med-El cochlear
      implants modified to record voltage difference from the apical and proximal
      electrodes were implanted into an unembalmed, fresh cadaver. Cautery was applied
      to the ipsilateral pectoralis major muscle and ipsilateral temporalis muscle at
      bipolar, monopolar coagulation, and monopolar cut settings of 50 W. The intensity
      in each modality setting was increased by increments of 10 W to a maximum of 100
      W. Integrity testing was performed before, during, and after each cautery
      setting. Voltage fluctuations were measured during cautery, and maximal voltage
      changes for each setting were noted. After explantation, devices were returned to
      the manufacturer for in-depth failure analysis to evaluate for any damage to the
      devices. SETTING: Tertiary medical center. SUBJECTS: Cadaveric study. METHODS:
      Basic science laboratory. RESULTS: No change in impedance or integrity testing
      occurred at any cautery setting when applied to either to pectoralis major or
      temporalis. The maximum voltage change was 22 V. Comprehensive device analysis
      showed no evidence of device damage from the study. CONCLUSIONS: The cochlear
      implant devices had no evidence of electrical damage by monopolar cautery, even
      up to levels of 100 W in the temporalis muscle. The maximum voltage change was 22
      V, likely resulting from protecting diodes within the implant. Additional study
      is necessary, but more flexible recommendations regarding electrosurgery in
      cochlear implant recipients should be considered.

PMID- 25569367
TI  - Distribution of melanocytes in the human cochlea.

PMID- 25569368
TI  - Study of the feasible size of a bone conduction implant transducer in the
      temporal bone.
AB  - HYPOTHESIS: The aim was to assess the temporal bone volume to determine the
      suitable size and position of a bone conduction implant (BCI) transducer.
      BACKGROUND: A BCI transducer needs to be sufficiently small to fit in the mastoid
      portion of the temporal bone for a majority of patients. The anatomical geometry
      limits both the dimension of an implanted transducer and its positions in the
      temporal bone to provide a safe and simple surgery. METHODS: Computed tomography
      (CT) scans of temporal bones from 22 subjects were virtually reconstructed. With
      an algorithm in MATLAB, the maximum transducer diameter as function of the
      maximum transducer depth in the temporal bone, and the most suitable position
      were calculated in all subjects. RESULTS: An implanted transducer diameter of 16
      mm inserted at a depth of 4 mm statistically fitted 95% of the subjects. If
      changing the transducer diameter to 12 mm, a depth of 6 mm would fit in 95% of
      the subjects. The most suitable position was found to be around 20 mm behind the
      ear canal. CONCLUSION: The present BCI transducer casing, used in ongoing
      clinical trials, was designed from the results in this study, demonstrating that
      the present BCI transducer casing (largest diameter [diagonal]: 15.5 mm, height:
      6.4 mm) will statistically fit more than 95% of the subjects. Hence, the present
      BCI transducer is concluded to be sufficiently small to fit most normal-sized
      temporal bones and should be placed approximately 20 mm behind the ear canal.

PMID- 25569370
TI  - Middle ear and mastoid obliteration for cochlear implant in adults: indications
      and anatomical results.
AB  - AIM OF THE STUDY: To review indications, anatomical results, and complications of
      cochlear implant (CI) surgery in adults for which middle ear and mastoid
      obliterations were performed. PATIENTS AND METHODS: Thirty cases (26 patients, 4
      bilaterally implanted) of 837 CI surgeries (3.5%) performed between January 2009
      and December 2013 have been included in this retrospective study. The mean follow
      up was 21 +/- 18 months (mean +/- SD, range 3-58). There were 11 males and 15
      females. The mean age was 59 +/- 19 years (range 35-82). All surgeries were
      performed with a single-stage technique including a canal wall down mastoidectomy
      with external auditory canal closure and mastoid obliteration with fat. A
      postoperative CT scan was performed in all cases. RESULTS: Etiologies of hearing
      loss were mainly chronic otitis with or without cholesteatoma in 24 cases. Other
      etiologies were meningitis with cochlear ossification in one case, progressive
      hearing loss in two cases, enlarged vestibular aqueduct in one case, temporal
      bone fracture with CSF leak in one case, and congenital aural atresia in one
      case. Four of those 30 cases were revision CI surgery for electrode array
      misplacement (one case with cochlear ossification) or extrusion from an open
      cavity (one case) and recurrent cholesteatomas (two cases). All surgeries were
      uneventful and performed in a single stage. The electrode array was inserted in
      the basal turn (29 cases) or in the middle turn (one case) of the cochlea. No
      complications were observed. Two cases of postoperative abdominal hematoma were
      drained under local anesthesia. A major failure of the CI device occurred 5
      months after surgery. CONCLUSION: CI with mastoid and middle ear obliteration is
      a safe and effective technique for selected cases of cochlear implantation.
      Mastoid obliteration prevents from recurrent disease and lowering the facial
      ridge allows more space to manage extensive cochlear ossification or
      malformation.

PMID- 25569369
TI  - Association between saccular function and gait speed: data from the Baltimore
      Longitudinal Study of Aging.
AB  - OBJECTIVE: To investigate whether otolith function (saccular and utricular) is
      associated with walking performance. STUDY DESIGN: Cross-sectional analysis of
      observational data collected in the Baltimore Longitudinal Study of Aging.
      SETTING: National Institute on Aging Intramural Research Program Clinical
      Research Unit at Harbor Hospital, Baltimore, Maryland. PATIENTS: Community
      dwelling participants. INTERVENTION(S): Cervical and ocular vestibular evoked
      myogenic potentials (VEMPs) were used to assess saccular and utricular function,
      respectively. MAIN OUTCOME MEASURE(S): Cervical and ocular VEMP latency and
      amplitude responses and usual, rapid, and narrow (20 cm) gait speed assessed over
      a 6-m course. RESULTS: In 314 participants (mean age, 73.1 yr; range, 26-96 yr),
      cervical VEMP amplitude mediated the association between age and gait speed
      particularly narrow walk speed-in both men and women. Cervical VEMP latency had
      an independent association with gait speed in age-, height-, and weight-adjusted
      analyses, although the direction of the association differed by sex. Greater
      cervical VEMP latency was associated with slower usual, rapid, and narrow gait
      speed in women but faster rapid gait speed in men. Neither the amplitude nor
      latency of ocular VEMP was associated with gait speed in men or women.
      CONCLUSION: These findings suggest that age-related slowing of gait speed is in
      part mediated by the decreased magnitude of saccular response associated with
      age. The sex-related differential association between saccular response latency
      and gait speed requires further study.

PMID- 25569371
TI  - Retained dental needle migration across the skull base to the cochlea presenting
      as hearing loss.
AB  - OBJECTIVES: Long-term retained foreign bodies in the human body have been
      reported across many specialties, but relatively few exist in the ENT literature.
      PATIENTS: We present a case report of a patient with a broken dental needle
      fragment in the posterior oral cavity with subsequent migration to the cochlea
      over the course of 4 years, eventually leading to hearing loss. CT scan and
      middle ear exploration demonstrated a 4-cm metallic fragment abutting the base of
      the cochlea, immediately adjacent to the internal carotid artery. INTERVENTIONS:
      The needle segment was removed through an endaural approach without complication.
      RESULTS: Postoperatively, the patient had improvements in PTA and speech
      discrimination, as well as the resolution of chronic otalgia and jaw pain.
      Imaging, audiologic results, and surgical details and pictures are presented
      herein. CONCLUSION: To our knowledge, based on a thorough PubMed and Google
      Scholar search, there are no reports of such a foreign body migration from the
      oral cavity to the skull base.

PMID- 25569372
TI  - Surfactant-free Pd nanoparticles immobilized to a metal-organic framework with
      size- and location-dependent catalytic selectivity.
AB  - Surfactant-free Pd nanoparticles, immobilized to a metal-organic framework (MIL
      101), have been used for the first time as highly active and durable catalysts in
      water for biomass refining (hydrodeoxygenation of vanillin, a typical compound of
      lignin) with metal nanoparticle size- and location-dependent catalytic activity
      and selectivity. 

PMID- 25569373
TI  - High expression level of antioxidants and pharmaceutical bioactivities of
      endophytic fungus Chaetomium globosum JN711454.
AB  - In order to maximize antioxidant activity of pharmaceutical bioactive endophytic
      fungus Chaetomium globosum JN711454 during fermentation process, designed
      fermentation experiments of culture media for three levels of eight culture
      factors were performed using a Taguchi orthogonal array (OA) design with layout
      L18 (2(1) * 3(7)). The agitation and the potato extract were the most significant
      affecting factors, and their interaction contributed significantly to fungus
      activity. The production of antioxidants was more favorable for static condition
      with 25 g potato extract/100 m. The remaining factors had no strong impact when
      considered individually. The validation of statistically optimized medium
      indicated the improvement of antioxidant activity to a level of twofold with
      approximately overall 40% enhancement in activity. The extract of optimized
      medium was investigated for various pharmaceutical bioactivities; it revealed a
      moderate antimicrobial activity, strong anticancer activity against HepG-2,
      UACC62 cell lines, an antiviral activity against HSV-2 virus, and strong
      inhibitory activity to butyrylcholinesterase enzyme, one of the neurohydrolase
      enzymes that play a major role in development of Alzheimer's disease. As a result
      of applying statistical fermentation designs, the optimized conditions of
      endophytic fungus C. globosum JN711454 developed a cost-effective production
      medium by using inexpensive commercial potato extracts statically, which can
      lower the energy requirement and could become an efficient, economic, and viable
      fermentation process for production of pharmaceutical secondary metabolites.

PMID- 25569374
TI  - Hepatocarcinoma cell-derived hepatoma-derived growth factor (HDGF) induces
      regulatory T cells.
AB  - BACKGROUND AND AIMS: It is suggested that regulatory immune cells play a critical
      role in cancer cell growth by facilitating cancer cells to escape from the immune
      surveillance. The generation of the immune regulatory cells in cancer has not
      been fully understood yet. This study aims to investigate the role of the
      hepatoma-derived growth factor (HDGF) in the generation of regulatory T cells
      (Treg). METHODS: CCL-9.1 cells (A mouse hepatoma cell line), were cultured. The
      expression of HDGF in CCL-9.1 cells was assessed by quantitative RT-PCR and
      Western blotting. The generation of Foxp3(+) T cells was assessed by cell culture
      and flow cytometry. The immune suppressor function of the Foxp3(+) T cells on
      CD8(+) T cell activities was assessed by the carboxyfluorescein succinimidyl
      ester (CFSE)-dilution assay and enzyme-linked immunosorbent assay. RESULTS: The
      results showed that exposure to PolyIC markedly increased the expression of HDGF
      in CCL-9.1 cells. Coculture of CCL-9.1 cells and CD4(+) CD25(-) T cells in the
      presence of PolyIC generated the Forkhead box protein (Foxp)3(+) T cells. The
      exposure to HDGF increased the expression of Foxp3 and decreased the expression
      of GATA3 in CD4(+) T cells. After activation, the Foxp3(+) T cells suppressed the
      CD8(+) T cell proliferation and the release of the cytotoxic cytokines.
      CONCLUSIONS: Liver cancer cell-derived HDGF can induce Foxp3(+) T cells; the
      latter has the immune suppressor functions on CD8(+) T cell activities.

PMID- 25569375
TI  - Serum IL-6, IL-10, and TNFalpha levels in pediatric sickle cell disease patients
      during vasoocclusive crisis and steady state condition.
AB  - Vaso-occlusive crisis (VOC) is a significant complication of sickle cell disease
      (SCD), and altered production of pro-inflammatory and anti-inflammatory molecules
      contributed to its pathogenesis. In view of the association of chronic
      inflammation with VOC onset, and given the capacity of interleukin (IL)-10 as
      anti-inflammatory, and IL-6, and TNFalpha as pro-inflammatory cytokines, we
      tested the association of altered IL-10, IL-6, and TNFalpha secretion with VOC
      pathogenesis and its severity. Study subjects comprised 147 SCD patients with
      active VOC (VOC Group), and 63 pain-free SCD patients for at least 9 months
      before blood collection (Steady-state Group). Serum cytokine concentrations were
      determined by ELISA. IL-10 levels were significantly reduced, while IL-6 levels
      were increased in VOC compared to Steady-state groups; serum TNFalpha levels were
      comparable between both groups. There was enrichment of low IL-10, but high IL-6
      and TNFalpha quartiles in VOC Group, which translated into increased VOC risk. In
      contrast, high IL-10, but low IL-6 and TNFalpha quartiles were seen in Steady
      state Group. Correlation analysis demonstrated significant association between
      reduced IL-10 levels and the frequency, type, severity, and duration of VOC and
      requirement for hydroxyurea treatment, while IL-6 correlated with duration of VOC
      episodes. Our data support strong association of reduced IL-10 and increased IL-6
      levels with VOC, and their modulation of VOC-related parameters.

PMID- 25569377
TI  - Multiple biopsies improve cervical cancer detection in colposcopy.

PMID- 25569376
TI  - Invariant natural killer T cells generated from human adult hematopoietic stem
      progenitor cells are poly-functional.
AB  - Invariant natural killer T (iNKT) cells constitute an important subset of T cells
      that can both directly and indirectly mediate anti-tumor immunity. However,
      cancer patients have a reduction in both iNKT cell number and function, and these
      deficits limit the potential clinical application of iNKT cells for cancer
      therapy. To overcome the problem of limited iNKT cell numbers, we investigated
      whether iNKT cells can be generated in vitro from bone marrow-derived adult
      hematopoietic stem-progenitor cells (HSPC). Our data demonstrate that co-culture
      of HSPC with OP9-DL1 stromal cells, results in a functional CD3(+) T cell
      population. These T cells can be further differentiated into iNKT cells by
      secondary culture with CD1d-Ig-based artificial antigen-presenting cells (aAPC).
      Importantly, these in vitro-generated iNKT cells are functional, as demonstrated
      by their ability to proliferate and secrete IFN-gamma and GM-CSF following
      stimulation. 

PMID- 25569379
TI  - HIF-1alpha and VEGF: Immunohistochemical Profile and Possible Function in Human
      Aortic Valve Stenosis.
AB  - Calcific aortic stenosis (CAS) is the most common valvular disease in Western
      countries. Histological findings in patients with CAS extremely resemble those of
      atherosclerosis and include accumulation and modification of lipoproteins,
      inflammation, extracellular matrix remodeling, and calcification. Angiogenesis is
      another prominent feature of CAS; however, there is only a limited amount of data
      available regarding the mechanisms behind the pathological neovascularization of
      a structure that is originally avascular. The present study aims to identify the
      molecular basis that regulates blood vessel growth in stenotic aortic valves,
      focusing on the role of HIF-1alpha and VEGF pathway. A total of 19 native
      degenerating aortic valves obtained at valve replacement surgery have been
      processed for Western blot, immunohistochemical, morphometric, and
      ultrastructural analyses. First, we have demonstrated the adverse ECM remodeling
      and the significant thickening of the leaflet also showing that HIF-1alpha and
      VEGF are significantly upregulated in the stenotic valves, are locally produced
      and colocalize with angiogenesis and areas of calcification. Next, we have
      characterized, for the first time to the best of our knowledge, the morphological
      features of the neovasculature evidencing the presence of intact blood vessels in
      close proximity to the mineralized zones. These results suggest that the complex
      structural remodeling of the matrix might reduce oxygen availability in the valve
      cusp contributing to the stabilization of HIF-1alpha that in turn induces a
      metabolic adaptation through the upregulation of VEGF and the formation of new
      blood vessels not only to overcome the hypoxic state but also to sustain the
      calcification process. 

PMID- 25569380
TI  - The cranial vault configuration is an integral part of the practice of
      craniofacial surgery.

PMID- 25569378
TI  - The distinct functions of CENP-C and CENP-T/W in centromere propagation and
      function in Xenopus egg extracts.
AB  - The centromere is the chromosomal region in which the kinetochore is assembled to
      orchestrate chromosome segregation. It is defined by the presence of a histone H3
      variant called Centromere Protein A (CENP-A) or CenH3. Propagation of centromere
      identity entails deposition of new CENP-A upon exit from mitosis in vertebrate
      cells. A group of 16 proteins that co-immunoprecipitate with CENP-A, the
      Constitutive Centromere Associated Network or CCAN, contribute to kinetochore
      assembly and function. For most of them it is still unclear how and when they are
      recruited to centromeres and whether they have a role in CENP-A deposition.
      Taking advantage of the Xenopus egg cell-free system, we have addressed these
      issues for CCAN proteins CENP-C, CENP-T and CENP-W. CENP-C recruitment occurs as
      soon as sperm DNA, containing CENP-A, is added to the egg extract, and continues
      after de novo incorporation of CENP-A in early interphase. In contrast,
      centromeric recruitment of CENP-T occurs in late interphase and precedes that of
      CENP-W, which occurs in mitosis. Unlike CENP-C, CENP-T and CENP-W do not
      participate in CENP-A deposition. However, like CENP-C, they play a major role in
      kinetochore assembly. Depletion of CENP-C results in reduced amount of CENP-T at
      centromeres, an effect more prominent in mitosis than in interphase. In spite of
      this, kinetochores can still be assembled under this condition although the
      recruitment of Ndc80 and Mis12 is decreased. Our results support the existence of
      2 pathways for kinetochore assembly directed by CENP-C and CENP-T/W, which can be
      reconstituted in Xenopus egg extracts. 

PMID- 25569381
TI  - Expanding the phenotypic expression of Sonic Hedgehog mutations beyond
      holoprosencephaly.

PMID- 25569382
TI  - Ethical considerations for surgeons.

PMID- 25569384
TI  - Long-term morphological outcomes in nonsyndromic sagittal craniosynostosis: a
      comparison of 2 techniques.
AB  - Correction of scaphocephaly is one of the principle goals of surgery in sagittal
      craniosynostosis. Reported relapse in head shape after surgery and continued head
      growth into late adolescence underscores the need for long-term outcomes to be
      considered when comparing between different surgical approaches in this
      condition; yet there are relatively few reports of results to 5 years and beyond
      in the literature. Therefore, a retrospective review was performed of the
      anthropometric data of 224 patients with sagittal craniosynostosis who underwent
      primary surgery between 1994 and 2012. During this period, patients underwent
      either a modified strip craniectomy (MSC) or calvarial remodeling (CR) procedure.
      Sixty-two patients were treated by MSC and followed up for a mean of 44 months.
      One hundred sixty-two patients had CR, with follow-up for a mean of 45 months.
      Overall, 90 patients were seen up to 5 years, and 47 patients to 9 years or more
      after surgery. The cephalic index (CI) of MSC-treated patients improved from a
      mean of 67.0 to 72.7, with 31% achieving a CI greater than 75 at one year.
      Calvarial remodeling was significantly more effective at correcting the
      scaphocephalic deformity. Patients treated with CR improved from a mean CI of
      66.7 to 76.1. Sixty-two percent of the patients achieved a CI greater than 75. In
      both groups, outcomes were stable throughout follow-up with no significant
      relapse up to 14 years after surgery. 

PMID- 25569383
TI  - Management of craniofacial chondroid tumors.
AB  - BACKGROUND: Craniofacial chondroid tumors (CFCTs) constitute less than 1% of all
      intracranial mass lesions. No protocol for evaluation and management of CFCTs is
      developed at the moment. MATERIALS AND METHODS: We analyzed 51 patients with
      CFCTs operated on in Burdenko Neurosurgical Institute from 1980 until 2012, which
      included chondroma (15), chondroblastoma (3), chondromyxoid fibroma (11), and
      chondrosarcoma (22). Age varied from 2 to 76 years (mean, 40 y); the series
      included 23 women and 28 men. All tumors were divided into 4 groups: midline
      unilateral (8),midline bilateral (21), anterolateral (19), and lateral (3). This
      division was based on differences in surgical approaches (P = 0.009). RESULTS:
      All patients underwent surgical treatment. Complete removal was achieved in 20;
      subtotal, in 21; and partial, in 10. Two patients died, and early complications
      were observed in 10 cases. Early outcomes correlated with the benign nature of
      the tumors (P = 0.002). Follow-up data were available in 22 patients. Fifteen of
      51 patients were reoperated on because of recurrence (a total of 43 reoperations
      were performed). The mean recurrence-free period was 45 months. In 3 patients,
      the tumor metastasized, and malignant transformation was observed in 3 cases.
      Sixteen patients received postoperative radiation therapy. Delayed sequelae
      occurred in 5 observations, and 5 patients died during long-term follow-up. Three
      year survival in benign and malignant tumors was 87.5% and 55.6%, respectively,
      and 5-year survival was 83.3% and 40.0%, respectively. CONCLUSION: Surgical
      resection is the mainstay in treatment of both benign and malignant craniofacial
      tumors, and adjuvant radiation therapy is mandatory in malignant lesions;
      however, it should be avoided in benign lesions.

PMID- 25569385
TI  - Systematic review of interventions for minimizing perioperative blood transfusion
      for surgery for craniosynostosis.
AB  - BACKGROUND: Surgery for craniosynostosis is associated with the potential for
      significant blood loss. Multiple technologies have been introduced to reduce the
      volume of blood transfused. These are preoperative autologous donation;
      preoperative erythropoietin; intraoperative cell salvage (CS); acute normovolemic
      hemodilution; antifibrinolytic drugs such as tranexamic acid, epsilon
      aminocaproic acid, and aprotinin; fibrin sealants or fibrin glue; and
      postoperative drain reinfusion. METHODS: All comparative studies with a treatment
      group and a control group were considered. There was a range of different study
      types from randomized controlled trials to case series with historic controls.
      These were intervention versus no intervention or a comparison of 2
      interventions. Studies were identified by searching Cochrane CENTRAL, MEDLINE,
      and EMBASE; manufacturer's Web sites; and bibliographies of relevant published
      articles. The primary outcome measures were the number of allogeneic blood donor
      exposures, the volume of allogeneic blood transfused, and the postoperative
      hemoglobin or hematocrit levels. RESULTS: A total of 696 studies were identified.
      After removal of duplicates and after exclusion criteria were applied, there were
      18 studies to be included. Fourteen were case series with controls and 4 were
      randomized controlled trials. CONCLUSIONS: The production of high-quality
      evidence on the interventions to minimize blood loss and transfusion in children
      undergoing surgery for craniosynostosis is difficult. Most of the literature is
      nonrandomized and noncomparative. Several areas remain unaddressed.
      Erythropoietin and tranexamic acid are comparatively well studied; CS, acute
      normovolemic hemodilution, and aprotinin are less so. There is only 1 comparative
      study on the use of fibrin glue and drain reinfusion, with no studies on
      preoperative autologous donation and [Latin Small Letter Open E]-aminocaproic
      acid. Tranexamic acid is clinically effective in reducing allogeneic blood
      transfusion. There is some evidence that CS and erythropoietin may be clinically
      effective. None of the interventions studied are shown to be cost-effective
      because of lack of evidence.

PMID- 25569386
TI  - Aesthetic occiput augmentation using methylmethacrylate.
AB  - Cranioplasty for only aesthetic reasons has not been commonly performed to date.
      However, recently there has been a new focus by the public on a more
      aesthetically pleasing head shape with frequent patient requests for purely
      aesthetic contouring of the occiput, an important definer of cosmetic head shape.
      For example, in Asia, where the normal cranial shape is mesocephalic or
      brachycephalic and often with a planar occiput, requests for its aesthetic
      correction are increasingly common. Accordingly, the author developed a minimally
      invasive occiput augmentation using methylmethacrylate. In this study, the
      indications for aesthetic occiput contouring were planar occiput, left-right
      asymmetric occiput, and grooved occiput. Under local anesthesia, soft
      methylmethacrylate is subperiosteally inserted through a small incision (about 5
      cm length), manually and precisely contoured in situ through the scalp to the
      desired occipital shape. All is performed as an outpatient procedure, and a quick
      recovery is the case. Between March 2007 and October 2013, 959 patients received
      such aesthetic occiput augmentation. The mean follow-up period was 49 months
      (range, 3-84 months). Nearly all patients were satisfied with the outcome, and
      complications were very rare. Only 5 patients (0.5%) needed additional corrective
      procedures. The author has concluded that aesthetic occiput augmentation using
      methylmethacrylate yields consistent, predictable, and satisfactory results.
      Additional long-term follow-up is required for a final conclusion, however. 

PMID- 25569387
TI  - Long-term follow-up study of radial forearm free flap reconstruction after
      hemiglossectomy.
AB  - Previous studies on postoperative long-term results in patients who underwent
      reconstructive free flap transfer following hemiglossectomy had some issues,
      including the heterogeneity of the patient population and the observation period.
      The present study aimed to evaluate changes of reconstructed tongues in patients
      who underwent radial forearm free flap (RFFF) after hemiglossectomy with long
      term follow-up. We enrolled 23 patients who underwent RFFF after hemiglossectomy
      with a postoperative follow-up of 5 years or more. Postoperative status (eating,
      speech, sensation function) was assessed by concise medical inquiries.
      Morphological changes of flaps were evaluated by reviewing clinical photographs.
      Hemiglossectomy involving the base of the tongue was performed in 4 cases (17.4%)
      and was limited to the mobile tongue in 19 cases (82.6%). The mean follow-up was
      85.4 months (range, 60-122 months). All patients experienced gradually improved
      postoperative status. The most significant improvement was found between 1 and 5
      years after surgery (P = 0.007), but not between 1 and 3 years (P = 0.075) or
      between 3 and 5 years (P = 0.530). In almost all of the flaps, there were few
      morphological changes throughout the follow-up period. Postoperative status in
      patients who underwent reconstructive RFFF following hemiglossectomy improved
      sequentially. 

PMID- 25569388
TI  - Estimation of eighth costal cartilage in surgical timing of microtia
      reconstruction.
AB  - There is controversy over the optimal timing of microtia reconstruction. The
      eighth costal cartilage, which is used to shape the helix framework, can be one
      of the key factors determining surgical timing of microtia reconstruction.
      Nevertheless, it is difficult to predict the length of the eighth costal
      cartilage preoperatively. The aim of the present study was to suggest clinical
      predictors of the length of the eighth cartilage by assessing the correlation
      between the actual length of the eighth cartilage and preoperative measurements
      of the cartilage length using three-dimensional rib-cage computed tomography (3D
      rib-cage CT). A retrospective analysis was performed on a total of 97 patients
      who underwent preoperative 3D rib-cage CT and auricular reconstruction using a
      rib cartilage graft between January 2010 and February 2013. The length of the
      eighth costal cartilage on 3D rib-cage CT was measured preoperatively, and the
      length of the harvested eighth rib cartilage was measured intraoperatively. We
      analyzed the association between the preoperative and intraoperative measured
      length of the eighth rib, with patient age, height, weight, and body mass index.
      Preoperative measurement using 3D rib-cage CT showed a high correlation with
      actual cartilage length. Height and weight correlated more strongly with length
      than with age. This study describes the usefulness of 3D rib-cage CT for
      preoperative measurement of the length of the eighth costal cartilage. The
      measurement of the eighth rib cartilage on 3D rib-cage CT could be a useful aid
      for reconstructive surgeons in planning microtia reconstruction. 

PMID- 25569389
TI  - Uncinatotomy: performing endoscopic sinus surgery without an uncinectomy.
AB  - BACKGROUND: The results of endoscopic sinus surgery performed for chronic
      rhinosinusitis are controversial. For a better surgical outcome, different
      surgical techniques involving an uncinectomy as the primary step of the operation
      have been proposed. The surgery should resolve the pathophysiologic problems
      caused by the disease and preserve the normal anatomy and physiology. We
      developed a technique to remove the pathology localized to isolated maxillary and
      anterior ethmoid cells, without excising the uncinate process. The infundibular
      area was exposed with medialization of the uncinate with a bipedicle flap
      prepared 1.5 cm from the insertion of the uncinate to the nasal wall, and then
      the sinus pathology was removed. At the end of the surgery, the uncinate was
      returned to its original position. METHODS: We performed this new technique to 3
      patients and evaluated postoperative results. RESULTS: Primary disease was
      eradicated, and no complication was noted. CONCLUSIONS: With this technique, it
      is possible to perform all steps of sinus surgery without excising any anatomic
      structure.

PMID- 25569390
TI  - Ophthalmic findings in children with nonsyndromic craniosynostosis treated by
      expansion cranioplasty.
AB  - The ocular and systemic abnormalities of nonsyndromic craniosynostosis are often
      considered to be less severe than those of syndromic craniosynostosis and are
      less well described. The purpose of this article was to describe the frequency
      and nature of ophthalmic abnormalities in children treated for nonsyndromic
      craniosynostosis by expansion cranioplasty. A retrospective review identified 88
      consecutive children with nonsyndromic craniosynostosis who underwent expansion
      cranioplasty with distraction osteogenesis. Assessment of presence and type of
      strabismus, refractive error, and amblyopia before and 6 months after surgery was
      recorded. Children with a mean age of 24.4 months were treated for nonsyndromic
      craniosynostosis (27 with coronal and 61 with sagittal and/or lambdoid). One
      fourth of the patients had a fixation preference. Significant refractive errors
      were found in 45 (51%) of the 88 patients: hyperopia in 27%, myopia in 5%, and
      astigmatism in 35%. Anisometropia was present in 20%. Of the 85 patients who
      completed orthoptic examination, 48 (56%) had strabismus: exodeviation in 26%,
      esodeviation in 14%, and vertical deviation in 5%. Fourteen patients (16%) had
      abnormal head posture. Significant refractive error and strabismus were more
      likely to occur in cases with coronal synostosis. The procedures used for cranial
      vault expansion improved the abnormal head posture but did not affect the
      refractive error or ocular misalignment. Of children with nonsyndromic
      craniosynostosis who need neurosurgical correction, more than half were found to
      have significant refractive error and strabismus. Our findings support the
      importance of ophthalmic evaluation in these children. 

PMID- 25569391
TI  - Complications in 54 frontofacial distraction procedures in patients with
      syndromic craniosynostosis.
AB  - Patients with syndromic craniosynostosis manifest midfacial hypoplasia often
      treated by midfacial advancement. Benefits of midfacial advancement by
      distraction osteogenesis have been well studied; little is known about the
      perioperative morbidity of these procedures, specifically relating to device
      selection. This study compares the perioperative complications between semiburied
      and halo-type distraction osteogenesis of the midface. A retrospective review
      was performed on all patients with syndromic craniosynostosis who underwent
      midface distraction with semiburied- or halo-type external distractors.
      Demographic information and operative/postoperative course were reviewed.
      Complications were categorized as hardware-related, infectious, and either as
      major (requiring additional intervention) or minor (requiring medication only).
      Chi-squared and Fisher exact test were used to compare variables.From 1999 to
      2012, a total of 54 patients underwent midface distraction osteogenesis,
      including 23 patients with Apert syndrome, 19 patients with Crouzon syndrome, 10
      patients with Pfeiffer syndrome, and 2 patients with other craniofacial
      syndromes. Thirty-three patients underwent a total of 34 subcranial Le Fort III
      distraction procedures and 21 underwent 21 monobloc distraction procedures. The
      mean age during surgery was 8.0 (range, 4.0-17.7) years, whereas the mean time
      between distractor placement and removal was 102.9 days. Thirty procedures were
      performed with external halo-type distractors (18 Le Fort III and 12 monobloc
      distractions), whereas 25 were performed with buried midface distractors (16 Le
      Fort III and 9 monobloc distractions). There were no significant differences in
      diagnoses or interventions between the distraction devices. Of the 19 distractor
      related complications, there were a total of 10 (18.2%) in the halo group
      including 5 (9.1%) requiring separate operative intervention as well as 9 (16.4%)
      in the buried distractor group including 6 (10.1%) requiring separate operative
      intervention. Major infections were more common in the buried distractor group (n
      = 8) compared with the halo distractor group (n = 3) (P = 0.048). There were 4
      (7.3%) patients in the halo group who had malposition or transcranial pin
      migration related to postoperative positioning or falls and required operative
      repositioning. Frontofacial distraction is an important technique in patients
      with syndromic craniosynostosis. Higher rates of halo displacement requiring
      surgery are offset with lower rates of infections compared with buried
      distractors. 

PMID- 25569392
TI  - Analysis of morbidity and mortality in patients undergoing skull base
      reconstruction.
AB  - The relative rarity of skull base tumors has limited surgeons' ability to report
      on morbidity and mortality in a large and nationwide patient series. We aimed to
      assess the impact of reconstructive procedures on patients undergoing skull base
      surgery and to determine whether 30-day postoperative morbidity and mortality
      varied between patients who underwent reconstruction and those who did not. We
      performed a retrospective analysis using American College of Surgeons National
      Surgical Quality Improvement Program 2005 to 2012 databases. Chi-squared tests
      were used for categorical variables and t-tests were used for continuous
      variables. Multiple logistic regression analysis predicted the influence of
      preoperative and operative variables on complications. A total of 479 patients
      were included in our study; 199 patients received concurrent reconstruction.
      There was no statistically significant difference in wound complication,
      morbidity, length of total hospital stay, and mortality between the 2 groups. The
      reconstruction cohort showed significantly longer operative times (416.45
      [207.585] versus 319.99 [222.813] min, P = 0.001) and higher return to the
      operating room rate (13.6% versus 6.1%, P = 0.005). Reconstruction using pedicled
      flaps was associated with increased odds of wound complications (odds ratio,
      4.937; P = 0.023), and microsurgical reconstruction was associated with return to
      the operating room (odds ratio, 2.212; P = 0.015). According to logistic
      regression, dyspnea, diabetes mellitus, functional status, and tumor involving
      the central nervous system were associated with complications. This study is the
      first comprehensive analysis of reconstruction after skull base surgery.
      Additional measures involved in flap reconstruction are associated with an
      increase in operation time and return to the operating room rate but not with
      complications, morbidity, or mortality. 

PMID- 25569393
TI  - Deformational plagiocephaly and craniosynostosis: trends in diagnosis and
      treatment after the "back to sleep" campaign.
AB  - BACKGROUND: In 1992, the American Academy of Pediatrics discouraged prone
      sleeping positions because of its association with sudden infant death syndrome.
      After this was an increased incidence of deformational plagiocephaly (DP).
      METHODS: A retrospective review was completed for patients with DP and
      craniosynostosis seen by plastic surgeons at a tertiary medical center during a
      19-year period. Two groups of patients were evaluated before (1988-1995) and
      after (1996-2007) implementation of the "Back to Sleep" campaign. RESULTS: Of the
      5169 patients, those with craniosynostosis (n = 279) had a mean age at initial
      evaluation before and after 1996 of 12.4 versus 5.6 months (P = 0.0008). There
      was a trend of decreasing age at initial evaluation and first surgery after 1996.
      For patients with DP (n = 4890), the mean age at initial evaluation before and
      after 1996 was 11.5 versus 6.0 months (P = 0.10). There was a trend of decreasing
      age at initial evaluation and DP correction after 1996. The majority of patients
      had right-sided DP (50.2%), followed by left-sided (24.7%) and bilateral (18.9%).
      There was no significant difference in DP correction rate (67% versus 87%) or the
      mean age that DP was corrected (12.8 versus 11.8 mo) before and after 1996.
      Compared with 1996 to 1999, there was a 214% and 390% increase in DP referrals
      from 2000 to 2003 and 2004 to 2007. For craniosynostosis, there was a 27% and
      129% increase in referrals. CONCLUSIONS: The increasing incidence of DP since the
      Back to Sleep campaign is concerning, but a positive outcome is that patients are
      being referred and treated at a younger age.

PMID- 25569394
TI  - Impact of torticollis associated with plagiocephaly on infants' motor
      development.
AB  - OBJECTIVE: This study investigated whether torticollis (congenital or acquired)
      in infants with plagiocephaly affects the achievement of specific gross motor
      milestones. METHODS: A total of 175 infants affected by plagiocephaly with or
      without torticollis were recruited and included in this prospective trial.
      Anthropometric and clinical variables were recorded at baseline. The infants were
      included in a physiotherapy treatment program, and they were monthly assessed
      until hospital discharge. RESULTS: Significant differences (P < 0.05) were
      observed in the achievement of rolling over, crawling, and standing skills
      depending on the specific profile (plagiocephaly and plagiocephaly with
      congenital or acquired torticollis). After adjusting for the severity of the
      plagiocephaly and the age at referral, the torticollis was significantly (P <
      0.05) associated with crawling and standing skills. CONCLUSIONS: The findings
      suggest that the presence or absence of congenital or acquired torticollis is an
      important factor that affects gross motor development in infants with
      plagiocephaly.

PMID- 25569395
TI  - In vitro comparison of the effect of different slice thicknesses on the accuracy
      of linear measurements on cone beam computed tomography images in implant sites.
AB  - BACKGROUND AND AIMS: Use of dental implants in edentulous patients has become a
      common treatment modality. Treatment of such implants requires radiographic
      evaluation, and in most cases, several different imaging techniques are necessary
      to evaluate the height, width, and structure of the bone at the implant site. In
      the current study, an attempt was made to evaluate the accuracy of measurements
      on cone beam computed tomography (CBCT) images with different slice thicknesses
      so that accurate data can be collected for proper clinical applications.
      MATERIALS AND METHODS: In the present in vitro study, 11 human dry mandibles were
      used. The width and height of bone at the central, canine, and molar teeth areas
      were measured on the left and right sides by using digital calipers (as gold
      standard) and on CBCT images with 0.5-, 1-, 2-, 3-, 5-, and 10-mm slice
      thicknesses. Data were analyzed with SPSS 16, using paired t-test, Tukey test,
      and inter class correlation. RESULTS: Data were collected by evaluation of 11
      skulls and 63 samples on the whole. There were no significant differences in bone
      width in any area (P > 0.05). There were significant differences in bone height
      in the central and molar teeth areas (P = 0.02). The measurements were not
      significant only at 4-mm slice thickness option and 5-mm slice thickness option
      for height compared with the gold standard (P = 0.513 and 0.173, respectively).
      The results did not show any significant differences between the observers (P =
      0.329). CONCLUSION: The highest measurement accuracy of CBCT software program was
      observed at 4-mm slices for bone width and 5-mm slice thickness for bone height.

PMID- 25569396
TI  - Effects of open and endoscopic surgery on skull growth and calvarial vault
      volumes in sagittal synostosis.
AB  - BACKGROUND: There have been conflicting reports on how sagittal synostosis
      affects cranial vault volume (CVV) and which surgical approach best normalizes
      skull volume. In this study, we compared CVV and cranial index (CI) of children
      with sagittal synostosis (before and after surgery) with those of control
      subjects. We also compared the effect of repair type on surgical outcome.
      METHODS: Computed tomography scans of 32 children with sagittal synostosis and 61
      age- and sex-matched control subjects were evaluated using previously validated
      segmentation software for CVV and CI. Sixteen cases underwent open surgery, and
      16 underwent endoscopic surgery. Twenty-seven cases had both preoperative and
      postoperative scans. RESULTS: Age of subjects at computed tomography scan ranged
      from 1 to 9 months preoperatively and 15 to 25 months postoperatively. Mean age
      difference between cases and matched control subjects was 5 days. The mean CVV of
      cases preoperatively was nonsignificantly (17 mL) smaller than that of control
      subjects (P = 0.51). The mean CVV of postoperative children was nonsignificantly
      (24 mL) larger than that of control subjects (P = 0.51). Adjusting for age and
      sex, there was no significant difference in CVV between open and endoscopic cases
      postoperatively (beta = 48 mL, P = 0.31). The mean CI increased 12% in both
      groups. There was no significant difference in mean postoperative CI (P = 0.18)
      between the 2 groups. CONCLUSIONS: Preoperatively, children with sagittal
      synostosis have no significant difference in CVV compared with control subjects.
      Type of surgery does not seem to affect CI and CVV 1 year postoperatively. Both
      open and endoscopic procedures result in CVVs similar to control subjects.

PMID- 25569397
TI  - Awful face of the war-impacted smoke bomb capsule in the face and systemic
      toxicity: reports from the conflict in Syria.
AB  - In this study, a rare kind of injury due to smoke bomb capsule impaction to
      midface and under the cranial base is presented, and maneuvers to reduce
      mortality are discussed. Three male patients were presented with impacted smoke
      bomb capsules into the midface and under the cranial base structures. Midface
      structures, anterior cranial base, and, in 2 patients, unilateral eye were
      severely damaged. Two patients died after the initial emergency operations
      because their lung disease progressed to acute respiratory distress syndrome. One
      of the patients lived, and soft tissue reconstruction was achieved by using
      temporal transposition and cheek advancement skin flaps with split-thickness skin
      graft from donor site. However, craniofacial destruction is important in these
      patients; a multidisciplinary approach is needed for the treatment of direct
      smoke bomb injuries because the patients experienced chemical burn and acute
      trauma. The timing of maxillofacial reconstruction is also a question in these
      specific patients.

PMID- 25569399
TI  - Rotation technique of reduction malar plasty.
AB  - The 2 most common complications of reduction malarplasty are nonunion or malunion
      and cheek drooping. Because masseter muscle is attached from zygomatic process of
      the maxilla to inferior two thirds of the zygomatic arch, rigid fixation and
      intimate bone contact without creating a gap are crucial for reduction
      malarplasty.Mesial-clockwise rotation of the zygomaticomaxillary complex can
      produce intimate bone contact and facilitates reduction malarplasty. 

PMID- 25569398
TI  - Does perioperative steroid use improve clinical outcomes in open repair of
      craniosynostosis?
AB  - BACKGROUND: The benefits of routine perioperative steroid use to decrease facial
      edema, ecchymosis, pain, and reduced length of hospitalization have been reported
      for many procedures. The role of perioperative steroids after open
      craniosynostosis surgery remains understudied. The purpose of our study was to
      assess the safety and efficacy of perioperative steroid administration in open
      repair of craniosynostosis based on current published clinical evidence. METHODS:
      A systematic review of PubMed, EMBASE, ClinicalTrials.gov, and the Cochrane
      library databases using inclusion and exclusion criteria was performed for
      articles that studied the efficacy of perioperative steroid use in
      craniosynostosis patients receiving open cranial repair surgery. RESULTS: Our
      review yielded 149 unique citations. One hundred thirty-nine titles were excluded
      based on predefined criteria. Ten abstracts and 4 articles (n = 14) qualified for
      full-text screening. Two additional relevant articles were identified using
      references. Three observational studies were eligible for data abstraction. A
      Cohen kappa coefficient score of 0.88 demonstrated high interrater agreement
      throughout the screening process. Clinical benefits in this specific population
      observed were improved control of postoperative edema, earlier time to eye
      opening, and reduced length of hospital stay. The timing, method, and technique
      of steroid administration varied between studies. CONCLUSIONS: The reviewed
      literature supports a clinical benefit following administration of perioperative
      steroids for open repair surgery of craniosynostosis. However, the current level
      of evidence on safety and efficacy remains limited in rigor and volume. Further
      randomized trials are necessary prior to recommending routine steroid use in our
      study population. CLINICAL QUESTION/LEVEL OF EVIDENCE: therapeutic, level III.

PMID- 25569400
TI  - Where to fix in rejuvenation surgeries?: tensile strength of the periosteum.
AB  - The aim of this study is to elucidate the tensile strength of the periosteum
      relating to facial rejuvenation surgeries.Twelve hemifaces of 6 formalin-fixed
      Korean adult cadavers were used. Two horizontal incision lines were made 3 cm
      above the supraorbital rim and 1 cm below the infraorbital rim. Another 2
      vertical incisions were on the medial orbital rim and 2 cm lateral to the lateral
      orbital rim. Elevated flaps were turned over, and the undersurfaces of the
      periosteum were exposed. A silk string was passed below the periosteum with a 3
      mm bite and wound. A 3-cm loop was made, and this was pulled away using the
      tensiometer. The breaking strength was measured.The breaking strengths of the
      periosteum were different according to the location (P = 0.000, analysis of
      variation). The strongest point was 2 cm above the supraorbital rim at the medial
      one third of the orbit (14.05 [2.50] N) followed by 1 cm above the
      frontozygomatic suture (13.35 [4.70] N). The weakest point was the infraorbital
      rim at the lateral one third of the orbit (6.93 [3.76] N) followed by the lateral
      orbital rim at the level of the lateral canthus (7.60 [3.49] N). Breaking
      strengths of the periosteum of the medial side (11.44 [3.83] N) were
      significantly greater (P = 0.021, t-test) than the lateral side (9.32 [3.76] N).
      In the supraorbital area, the breaking strengths of the periosteum of the upper
      points (12.91 [3.00] N) were significantly greater (P = 0.000, t-test) than the
      lower points (9.36 [2.76] N).The results of this study can be of use when
      choosing a fixation point in rejuvenation surgeries. 

PMID- 25569401
TI  - The functional and histopathologic change in the levator palpebrae superioris and
      Muller muscle after subconjunctival injection of triamcinolone acetonide.
AB  - AIMS: The aim of this study was to evaluate the functional and histopathologic
      changes in the levator palpebrae superioris and Muller muscles after
      subconjunctival injection of triamcinolone acetonide (TA) in rabbits. METHODS:
      Twenty-four white New Zealand rabbits were divided into 2 groups. In group A, a
      subconjunctival injection of 0.5 mL TA (40 mg/mL) was administered to the right
      eye, whereas a normal saline injection of the same volume was administered to the
      left eye. In group B, the same procedures were done with a 1.0-mL injection of TA
      or normal saline into each eyelid. Follow-up was done to evaluate the
      histopathologic changes in the levator and Muller muscles, changes in the mean
      transectional area of Muller muscle, and changes in upper-lid height (marginal
      reflex distance 1) at 1, 2, 4, and 6 weeks after injection. Western blot analyses
      were used to determine the levels of myosin light chain phosphorylation and alpha
      smooth muscle actin, which are related to the contractility of Muller muscle.
      RESULTS: No specific changes in marginal reflex distance 1 were noted in either
      group A or B. No significant histopathologic changes were found in the levator
      muscles. However, significant thinning of Muller muscle were found, and myosin
      light chain phosphorylation and alpha-smooth muscle actin levels were decreased.
      This was consistent with the histologic changes of Muller muscle observed in
      rabbits that received a TA injection. These changes were reversible and
      influenced by the volume of the injection. CONCLUSIONS: Subconjunctival injection
      of TA into the upper eyelids appears to be temporally influential on both the
      functional and histopathologic changes of Muller muscle in rabbits. This may be
      explained by the effect of improvement in lid retraction regardless of the
      minimal specific change observed in the levator muscle.

PMID- 25569402
TI  - The effects of nonvascularized versus vascularized bone grafting on calvarial
      defect healing.
AB  - It remains unknown whether bone graft vascularity influences calvarial healing.
      The purposes of this study were (1) to develop a model to study nonvascularized
      and vascularized calvarial grafts as well as (2) to compare effects of bone graft
      vascularity on calvarial healing. Bilateral calvarial defects were created in 26
      Wistar rats. The defects were left empty within 1 parietal region. On the
      contralateral side, the defects were partially closed with native parietal bone
      (control group, n = 6), nonvascularized (N-V, n = 10), or vascularized bone
      grafts (VAS, n = 10). The vascularized grafts were supplied by perforating dural
      arterioles. Bone mineralization and healing patterns from serial microcomputed
      tomographic scans were compared within and across the groups using parametric and
      nonparametric tests. Differences in bone mineral content across sides were
      significant between the groups at weeks 6 (P = 0.016) and 12 (P = 0.025). Bone
      formation was greater within both the control and VAS groups versus the N-V group
      at weeks 6 and 12 (P < 0.05). Healing patterns differed between the groups (P <
      0.05), progressing through islands of new bone formation within the control and
      VAS groups while limited to defect margins on the N-V graft side. In conclusion,
      a bilateral calvarial defect model was established to study bone graft
      vascularity. Bone quantity and healing patterns differed in the presence of the
      nonvascularized versus vascularized grafts. Although the calvarial defect model
      is often applied within the plastic surgery literature to study bone substitutes,
      greater understanding of basic mechanisms influencing calvarial healing is first
      needed to avoid confounding results. 

PMID- 25569403
TI  - Late treatment of ocular globe displacement to the maxillary sinus after an
      orbital floor fracture.

PMID- 25569404
TI  - Existence of and predisposing factors for implant periapical lesions.

PMID- 25569405
TI  - Advanced Marjolin ulcer of the scalp with skull.

PMID- 25569406
TI  - Izogenic cartilage transfer in rhinoplasty procedure.
AB  - Cartilage is commonly grafted during primary and secondary rhinoplasties as a
      means of addressing both functional and esthetic issues. Generally, such grafts
      are taken from the nasal septum, but auricular conchae or ribs may serve as donor
      sites if needed. However, the latter often entail considerable morbidity and
      graft mismatch. To circumvent these drawbacks, use of implants or processed
      cartilage (allogenic or xenogenic in origin) has been proposed. Herein, the
      isogenic transfer of nasal septal cartilage between identical twins is reported. 

PMID- 25569407
TI  - Management of a transcranial abscess secondary to interleukin-1 receptor
      associated kinase 4 deficiency.
AB  - Interleukin-1 receptor associated kinase 4 (IRAK-4) deficiency is a primary
      immunodeficiency that predisposes to opportunistic pyogenic infections in
      affected patients. The presentation can be variable, and the microbiological and
      immunologic management of this condition has been documented; however, the
      atypical nature of its presentation calls for a different approach in its
      surgical management. This is the first reported case of transcranial progression
      of a soft tissue abscess in a patient with IRAK-4 deficiency, with an emphasis on
      a multidisciplinary approach to treat infection at an extremely vulnerable
      anatomic site. 

PMID- 25569408
TI  - Comparison of different administration of ketamine and intravenous tramadol
      hydrochloride for postoperative pain relief and sedation after pediatric
      tonsillectomy.
AB  - OBJECTIVES: Tonsillectomy is the oldest and most frequently performed surgical
      procedure practiced by ear, nose, and throat physicians. In this study, our aim
      was to compare the analgesic effects of peritonsillar, rectal, as well as
      intravenous infiltration of ketamine and intravenous tramadol hydrochloride
      infiltration for postoperative pain relief and sedation after tonsillectomy in
      children. MATERIALS AND METHODS: This randomized controlled study evaluated the
      effects of peritonsillar, intravenous, and rectal infiltration of ketamine in
      children undergoing adenotonsillectomy. One hundred twenty children who were
      categorized under American Society of Anesthesiologists classes I to II were
      randomized to 4 groups of 30 members each. Group 1 received intravenous (IV)
      ketamine (0.5 mg/kg), group 2 received rectal ketamine (0.5 mg/kg), group 3
      received local peritonsillar ketamine (2 mg/kg), and the control group received
      IV tramadol hydrochloride infiltration (2 mg/kg). Children's Hospital of Eastern
      Ontario Pain Scale scores and Wilson sedation scale were recorded at minutes 1,
      15, 30, 60 as well as hours 2, 12, and 24 postoperatively. The patients were
      interviewed on the day after the surgery to assess the postoperative pain and
      sedation. RESULTS: All the routes of infiltration of ketamine were as effective
      as those of tramadol hydrochloride (P > 0.05). A statistically significant
      difference was observed between IV infiltrations and all groups during the
      assessments at hours 6 and 24. The analgesic efficacy of IV ketamine was found
      especially higher at hours 6 and 24 (P(6) = 0.045, P(24) = 0.011). CONCLUSIONS:
      Perioperative, low-dose IV, rectal, or peritonsillar ketamine infiltration
      provides efficient pain relief without any adverse effects in children who would
      undergo adenotonsillectomy.

PMID- 25569409
TI  - Endoscopic removal of giant intranasal schwannoma.
AB  - Schwannoma is a benign neoplasm originating from schwann cells of the peripheral
      nerve sheath. Although nearly half of all schwannomas involve the head and neck
      region, nasal and paranasal sinus presentations are very rare in the literature.
      We present a case of nasal schwannoma originating from the right nasal cavity. A
      59-year-old man presented with complaints of progressive right nasal obstruction
      and headache. Endoscopic examinations revealed a mass that filled the right
      middle meatus. At first glance, it was not like polyp tissue. Endoscopic sinus
      surgery was performed under general anesthesia, and the mass was completely
      removed. 

PMID- 25569410
TI  - Metastatic follicular thyroid carcinoma masquerading as olfactory neuroblastoma:
      with skull-base, cranium, paranasal sinus, lung, and diffuse bone metastases.
AB  - Skull-base metastasis is rarely reported in thyroid carcinoma. We are presenting
      an unusual interesting case mimicking metastatic renal cell carcinoma with
      intense clear cell morphology, the thyroid origin of which was detected via
      positron emission tomography/computerized tomography scan proposed by the
      oncology council, while we were monitoring the subject with the initial diagnosis
      of paranasal sinus tumor. A mass was detected in the left nasal cavity in the
      endoscopic examination of the 68-year-old female patient referred by the
      ophthalmology clinic with the preliminary diagnosis of retro-orbital tumor upon
      being admitted with proptosis. A soft tissue lesion at a size of 68 * 39 * 53 mm
      located intracranially was detected by the brain computerized tomography. The
      biopsy taken and the immunohistochemical results were not satisfactory. Intense
      fluorodeoxyglucose involvement was observed in both lobes of the thyroid gland at
      positron emission tomography/computerized tomography taken with the
      recommendation of the council. Moreover, hypermetabolic nodules were seen in both
      lung parenchyma areas, whereas intense hypermetabolic lytic lesions were observed
      in the skeletal system. Thyroglobulin and thyroid transcription factor 1 stains
      displayed a strong staining on paraffin block. On the basis of these
      characteristics, the case was regarded as compatible metastatic follicular
      thyroid carcinoma, with skull-base, cranial, retro-orbital, paranasal sinus,
      lung, and bone metastases. This case showed us that multidisciplinary work and
      assessment of the oncology council play a highly critical role in making the
      diagnosis and guiding the treatment. 

PMID- 25569411
TI  - Branchiootorenal and branchiooculofacial syndrome.
AB  - INTRODUCTION: Branchiootorenal syndrome (BOR) is an autosomal dominant disorder.
      One of very similar syndromes is branchiooculofacial syndrome (BOF), with
      incomplete penetrance and variable expression. The overlap between BOR syndrome
      and BOF syndrome includes external ear abnormalities with hearing loss, lachrymal
      duct obstruction, branchial cleft remnants, and renal or urethral defects. The
      relationship between these 2 syndromes is still unclear. CASE OUTLINE: We present
      2 patients with these rare syndromes: a girl who has fulfilled the diagnostic
      criteria for BOR syndrome and a boy who has more than fulfilled the criteria for
      BOF syndrome. The diagnosis of BOF syndrome was performed only on the basis of
      clinical findings, without genetic confirmation. CONCLUSIONS: Differential
      diagnosis between these similar syndromes with phenotypic variation is delicate
      especially without genetic examinations.

PMID- 25569412
TI  - Neonatal mandibular distraction in a patient with Treacher Collins syndrome.
AB  - The purpose of this study was to analyze a case of mandibular distraction in a
      case of Treacher Collins syndrome. Mandibular distraction is an adequate surgical
      treatment of patients with Pierre Robin sequence and represents an alternative to
      tracheostomy. In severe hypoplastic cases or when three-dimensional vector
      control or gonial angle control is necessary, extraoral bidirectional or
      multidirectional devices have an advantage over intraoral devices. The anchorage
      obtained with transfixing Kirschner wires fixed in the mandibular distal segment
      and symphysis is crucial in neonates for the stability of the devices. Moreover,
      with the use of a second pin for each bone segment, the extraoral devices allow
      to modify the vector orientation and consequently the shape of the newly formed
      mandible. 

PMID- 25569413
TI  - Skin tension related to tension reduction sutures.
AB  - The aim of this study was to compare the skin tension of several
      fascial/subcutaneous tensile reduction sutures. Six upper limbs and 8 lower limbs
      of 4 fresh cadavers were used. At the deltoid area (10 cm below the palpable
      acromion) and lateral thigh (midpoint from the palpable greater trochanter to the
      lateral border of the patella), and within a 3 * 6-cm fusiform area of skin,
      subcutaneous tissue defects were created. At the midpoint of the defect, a no. 5
      silk suture was passed through the dermis at a 5-mm margin of the defect, and the
      defect was approximated. The initial tension to approximate the margins was
      measured using a tensiometer.The tension needed to approximate skin without any
      tension reduction suture (S) was 6.5 +/- 4.6 N (Newton). The tensions needed to
      approximate superficial fascia (SF) and deep fascia (DF) were 7.8 +/- 3.4 N and
      10.3 +/- 5.1 N, respectively. The tension needed to approximate the skin after
      approximating the SF was 4.1 +/- 3.4 N. The tension needed to approximate the
      skin after approximating the DF was 4.9 +/- 4.0 N. The tension reduction effect
      of approximating the SF was 38.8 +/- 16.4% (2.4 +/- 1.5 N, P = 0.000 [ANOVA,
      Scheffe]). The tension reduction effect of approximating the DF was 25.2% +/-
      21.9% (1.5 +/- 1.4 N, P = 0.001 [ANOVA, Scheffe]). The reason for this is thought
      to be that the SF is located closely to the skin unlike the DF. The results of
      this study might be a basis for tension reduction sutures. 

PMID- 25569414
TI  - Iatrogenic arteriovenous fistula of the superficial temporal artery after
      reduction malarplasty.
AB  - A 34-year-old woman who had a history of undergoing reduction malarplasty at a
      local clinic about 1 year ago developed gradually increasing pulsatile tinnitus
      in the right preauricular area since the last 6 months. On physical examination,
      there were an approximately 1 * 0.5-cm nontender, soft, pulsatile mass with a
      palpable thrill and a continuous machinery-like buzzing sound in synchrony with
      the heartbeat. She had a fine scar near the mass, which was supposed to be a
      postoperative scar of reduction malarplasty. A three-dimensional computed
      tomographic angiogram revealed a direct arteriovenous fistula between the
      superficial temporal artery and superficial temporal vein in the right
      preauricular area. The arteriovenous fistula was embolized using Tornado coils.
      After coiling, the thrill and disturbing tinnitus disappeared immediately, and
      postembolization angiography confirmed obliteration of the arteriovenous shunt.
      This is the first case of an arteriovenous fistula of the superficial temporal
      artery after reduction malarplasty, and it indicates that arteriovenous fistula
      can occur as a delayed complication of reduction malarplasty. 

PMID- 25569415
TI  - Recurrent ptosis in a patient with blepharochalasis: clinical and histopathologic
      findings.
AB  - A 37-year-old woman presented with right upper eyelid blepharochalasis with
      ptosis. Right upper eyelid edema had occurred 2 to 3 times per year by 30 years
      old, although the frequency decreased with age. The edema occurred spontaneously
      and resolved within 1 to 2 days. She underwent a right levator tucking surgery at
      22 years old, and the ptosis recurred 2 years postoperatively. She again
      underwent ptosis surgery with skin excision at 37 years old. The intraoperative
      findings showed a thin levator aponeurosis. The white line was therefore advanced
      to the upper tarsal edge, resulting in an appropriate height and curvature. Three
      months later, the patient's eyelid height was 1.5 mm higher with a little
      temporal peaking. The levator aponeurosis was histopathologically shown to
      contain many capillaries. The increased vascularity of the levator aponeurosis
      may contribute to recurrent bouts of edema resulting in stretching and
      disinsertion of the aponeurosis. 

PMID- 25569417
TI  - Robotic excision of a huge parathyroid adenoma via a retroauricular approach.
AB  - Primary hyperparathyroidism results from the overproduction of parathyroid
      hormone by 1 or more autonomously hyperfunctioning parathyroid glands and often
      causes hypercalcemia. Once this condition has been diagnosed, the treatment of
      choice is surgical removal. There have been many attempts to remove the
      hyperfunctioning gland with minimally invasive surgical techniques, with cure
      rates comparable with those of conventional techniques. On the basis of our
      initial surgical experiences of robotic thyroidectomy and other head and neck
      surgeries via a retroauricular (RA) approach, we have recently successfully
      performed robotic excision of a huge parathyroid tumor via an RA approach on a 44
      year-old woman who had been diagnosed with a parathyroid adenoma. It is the first
      to describe in detail the successful completion of a robotic parathyroidectomy
      via an RA approach. 

PMID- 25569416
TI  - Immediate reconstruction of the maxillary sinus after resection of preoperatively
      misdiagnosed unicystic ameloblastoma with an ectopic third molar.
AB  - We report a case of unicystic ameloblastoma associated with an ectopic third
      molar in the right maxillary sinus, which was misdiagnosed as a dentigerous cyst
      on preoperative small incisional biopsy. Surgical enucleation of the cystic
      lesion was performed under general anesthesia with immediate reconstruction of
      the maxillary sinus using titanium mesh plate. The patient's postoperative
      recovery was uneventful, and there was no evidence of tumor recurrence during the
      7-month follow-up period. 

PMID- 25569418
TI  - Asymptomatic intradiploic epidermoid cyst eroding frontal bone in a patient with
      craniosynostosis.
AB  - Epidermoid cyst located in cranium is uncommon and usually diagnosed with a
      growing mass leading to symptoms. Asymptomatic intradiploic epidermoid cyst has
      not been reported yet. In this study, incidental diagnosis of asymptomatic cyst
      and potential impact of that cyst on surgical planning of a patient with
      craniosynostosis are presented. 

PMID- 25569419
TI  - Completion of nonreducible Le Fort fractures by Le Fort I osteotomy: sometimes an
      inevitable choice to avoid postoperative malocclusion.
AB  - The aim of this study was to prospectively evaluate the use of a simultaneous Le
      Fort I osteotomy for completion of nonreducible Le Fort fractures. We analyzed
      the clinical and radiological data of 44 patients with Le Fort fractures, 9 of
      whom presented with a nonreducible type. Seven patients with an incomplete Le
      Fort I fracture had a contralateral Le Fort I osteotomy, and 2 patients with an
      incomplete Le Fort III fracture had a true bilateral Le Fort I-type osteotomy. We
      recorded age and sex, mechanism of injury, level of Le Fort fracture, concomitant
      mandibular fractures, concomitant maxillomandibular fixation (MMF) and its
      duration, surgical approach, status of healing, and complications. Follow-ups
      were at 1 week and 1, 3, 6, and 12 months.All patients recovered their normal
      pretrauma occlusion without the need for postoperative elastic guidance, except
      for 1 patient who required light class III traction elastics for 3 weeks to
      achieve the correct occlusion. None of the patients presented with intraoperative
      or postoperative complications.The present study has demonstrated that completion
      of nonreducible Le Fort fractures by Le Fort I osteotomy results in a high rate
      of success. 

PMID- 25569420
TI  - Orbital trapdoor fracture: can it occur also in adults?
AB  - We describe here a peculiar case of a 30-year-old woman presenting with an
      orbital trapdoor fracture. Preoperative and postoperative magnetic resonance
      images are provided to explain the mechanism of the injury. 

PMID- 25569422
TI  - Computed tomography image guidance for more accurate repair of anterior table
      frontal sinus fractures.
AB  - BACKGROUND: Anterior table frontal sinus fractures accompanied by nasofrontal
      duct injury require surgical correction. Extracranial approaches for anterior
      table osteotomies have traditionally used plain radiograph templates or a "cut-as
      you-go" technique. We compared these methods with a newer technique utilizing
      computed tomography (CT)-guided imaging. METHODS: Data of patients with acute,
      traumatic anterior table frontal sinus fractures and nasofrontal duct injury
      between 2009 and 2013 were reviewed (n = 29). Treatment groups compared were as
      follows: (1) CT image guidance, (2) plain radiograph template, and (3) cut-as-you
      go. Frontal sinus obliteration was performed in all cases. Demographics,
      operative times, length of stay, complications, and osteotomy accuracy were
      recorded. RESULTS: Similar demographics, concomitant injuries, operative times,
      and length of stay among groups were noted. No patients in the CT-guided group
      had perioperative complications including intraoperative injury of the dura,
      cerebrum, or orbital structures. In the plain radiograph template group, 25% of
      patients had inadvertent dural exposure, and 12.5% required take-back to the
      operating room for cranial bone graft donor site hematoma. In the cut-as-you-go
      group, 11% required hardware removal for exposure. There were no cases of
      cerebrospinal fluid leak, meningitis, or mucocele in any group (follow-up, 29.2
      months). The CT image guidance group had the most accuracy of the osteotomies
      (95%) compared with plain radiograph template (85%) and the cut-as-you-go group
      (72.5%). CONCLUSIONS: A new technique using CT image guidance for traumatic
      frontal sinus fractures repair offers more accurate osteotomy and elevation of
      the anterior table without increased operative times or untoward sequelae.

PMID- 25569421
TI  - Cranial base deviation in hemifacial microsomia by craniometric analysis.
AB  - Although facial asymmetry in hemifacial microsomia (HFM) is well documented in
      the literature, no studies have concentrated on the morphology of the cranial
      base. This study aimed to evaluate the endocranial morphology in patients with
      HFM. Consecutive patients with unilateral HFM treated at a craniofacial center
      from 2000 to 2012 were included. The patients were grouped according to severity
      on the basis of the Kaban-Pruzansky classification: mild (0-1), moderate (2a),
      and severe (2b-3). Skull base angulation and transverse craniometric measures
      were recorded and then compared with those of age-matched controls. A total of 30
      patients (14 males, 16 females) averaging 7.5 years of age (range, 1.1-15.7 y)
      were included. Four patients were classified as mild; 12, as moderate; and 14, as
      severe. The mean cranial base angle was found to be between 179 and 181 degrees
      with no significant difference between the severity groups (P = 0.57). The mean
      cranial base angle did not differ significantly in the patients compared with the
      controls(179.6 vs 180.0; P = 0.51) No significant differences between the
      affected and unaffected sides in the patients were found in distances from the
      midline to hypoglossal canal, internal acoustic meatus, lateral carotid canal,
      medial carotid canal, foramen ovale, and rotundum. There were no significant
      differences in transverse measurements between the severity classes using the
      same landmarks (P = 0.46, P = 0.30, P = 0.40, P = 0.25, P = 0.57, and P = 0.76,
      respectively). The cranial base axis is not deviated in the patients with HFM
      compared with the age-matched controls, and there exists little difference in
      endocranial morphologic measurements with increasing severity of HFM. These data
      are interesting, given the role of the cranial base in facial growth and the
      varying hypotheses regarding the mechanism of disease in HFM.

PMID- 25569423
TI  - Congenital maxillomandibular syngnathia: a new management technique using
      distraction techniques.
AB  - Complex zygomaticomandibular syngnathia is an extremely rare condition with an
      unknown etiology. The main goal of the surgery is to release the ankylosis,
      establish good functioning mandible, and prevent reankylosis, if possible. In our
      case, we offer a new solution to have an adequate oral opening and to prevent
      reankylosis. After the release of bony syngnathia, we placed a distractor between
      mandibular segment and maxillozygomatic complex. To our best knowledge, this is
      the only syngnathia case in the literature treated using distraction techniques.
      There is a major improvement in the patient's status. Distraction may broaden our
      horizons in this rare and difficult-to-treat deformity. 

PMID- 25569424
TI  - Posterior cranial vault distraction in the treatment of shunt-induced
      craniosynostosis.
AB  - Cerebrospinal fluid shunt placement is the most common surgical intervention for
      hydrocephalus. In rare cases, cerebrospinal fluid shunting has been associated
      with the development of secondary craniosynostosis. Posterior cranial vault
      distraction osteogenesis is an emerging technique used for the treatment of
      craniosynostosis. Posterior vault distraction allows greater intracranial volume
      expansion than do techniques that address the anterior cranium. We present a
      patient with shunt-induced multisuture craniosynostosis with delayed
      presentation. She was effectively treated with posterior cranial vault
      distraction and preservation of her ventriculoperitoneal shunt. This unique case
      demonstrates the safety and utility of this procedure for complex craniocerebral
      disproportion. 

PMID- 25569425
TI  - Endoscopic marsupialization of frontoethmoid mucocele with underlying
      craniofacial fibrous dysplasia.
AB  - Fibrous dysplasia (FD) is a benign progressive fibro-osseous lesion that is
      rarely associated with mucocele formation. This complication most probably
      results from the involvement and subsequent occlusion of the recesses of the
      sinuses by the dysplastic process. The frontoethmoid mucocele associated with FD
      represents a rare pathology, but it is important to consider this in the
      differential diagnosis of patients with proptosis, visual disturbance, and bony
      fronto-orbital swellings. Here, we describe the first case of frontoethmoid
      mucocele with underlying craniofacial FD, which was successfully treated by wide
      marsupialization via the transnasal endoscopic approach. 

PMID- 25569426
TI  - The hybrid approach for reconstruction of severely destructed lower eyelids:
      combination of skin grafting, temporary tarsorrhaphy, and autologous fat grafting
      for cicatricial ectropion after injection of commercial grade silicone.
AB  - BACKGROUND: Although silicone injections for permanent soft tissue augmentation
      were popular in the past, their use has become unduly controversial because of
      severe complications, mainly caused by injection of illegal silicones by
      unlicensed practitioners. The delicate local anatomy of the lower eyelid region
      makes this region particularly susceptible for complications after silicone
      augmentation including local inflammation, tissue retraction, and consecutive
      cicatricial ectropion leading to lagophthalmus and ocular surface irritation.
      CLINICAL REPORT: This is a case of a 47-year-old patient demonstrating severe
      lower eyelid destruction with consecutive ectropion after injection of commercial
      grade silicone in Thailand 5 years prior, leading to chronic granulomatous
      infections requiring multiple surgical interventions.Our hybrid approach included
      radical debridement with complete elimination of silicone residues, lateral
      canthopexy, reconstruction of the entire lower eyelid esthetic unit using a
      supraclavicular full-thickness skin graft, and temporary tarsorrhaphy followed by
      2 sessions of autologous fat graft injections.Although many previous publications
      mainly focus on individual aspects of lower eyelid reconstruction, we describe a
      staged reconstructive approach for correction of severely destructed lower eyelid
      defects with consecutive lower eyelid ectropion. CONCLUSIONS: The hybrid approach
      presented here has proven to be a viable surgical strategy for lower eyelid
      reconstruction, with esthetically appealing results.

PMID- 25569429
TI  - Real enough: using virtual public speaking environments to evoke feelings and
      behaviors targeted in stuttering assessment and treatment.
AB  - PURPOSE: Virtual reality environments (VREs) are computer-generated, 3
      dimensional worlds that allow users to experience situations similar to those
      encountered in the real world. The purpose of this study was to investigate VREs
      for potential use in assessing and treating persons who stutter (PWS) by
      determining the extent to which PWS's affective, behavioral, and cognitive
      measures in a VRE correlate with those same measures in a similar live
      environment. METHOD: Ten PWS delivered speeches-first to a live audience and, on
      another day, to 2 virtual audiences (neutral and challenging audiences).
      Participants completed standard tests of communication apprehension and
      confidence prior to each condition, and frequency of stuttering was measured
      during each speech. RESULTS: Correlational analyses revealed significant,
      positive correlations between virtual and live conditions for affective and
      cognitive measures as well as for frequency of stuttering. CONCLUSIONS: These
      findings suggest that virtual public speaking environments engender affective,
      behavioral, and cognitive reactions in PWS that correspond to those experienced
      in the real world. Therefore, the authentic, safe, and controlled environments
      provided by VREs may be useful for stuttering assessment and treatment.

PMID- 25569430
TI  - Using Enforcement and Adjudication Data to Assess the Impact of a Primary Safety
      Belt Law.
AB  - BACKGROUND: Identification of effective implementation strategies for motor
      vehicle injury prevention law is an important priority for research in public
      health law and policy. Extensive literature in related fields demonstrates the
      relationship between enforcement activities and achievement of safety objectives.
      PURPOSE: We conducted this study to determine the role of enforcement and
      adjudication in the implementation of a primary safety belt law, including the
      level and sustainability of safety belt-related conviction rates, using newly
      available data from the state judicial administrative authority. A secondary goal
      was to assess the contribution of the administrative data set to the analysis of
      the primary safety belt law. METHODS: The analysis used an interrupted time
      series design to evaluate the longitudinal effect of the primary safety belt law
      implementation in 2007 on safety belt infractions and convictions in Kentucky,
      2003-2012. Segmented regression analysis was used to estimate changes in the
      level and trend of safety belt nonuse conviction rate after the full
      implementation of the law, while controlling for the baseline level and trend.
      The association between the safety belt-related conviction rates and other
      expected outcomes of the law's implementation was studied. RESULTS: Safety belt
      citations doubled and convictions nearly tripled during the decade studied, most
      dramatically in the first year. Increases were sustained throughout the study
      period. There was a strong positive linear association between the safety belt
      nonuse conviction rate and the observed safety belt use in the state, as well as
      a strong negative association between the safety belt nonuse conviction rate and
      the number of nonrestrained motor vehicle crash fatalities. DISCUSSION: Our
      analysis demonstrates that Kentucky's public safety and judicial systems took the
      new law seriously and enforced it effectively and that the increased level of
      enforcement persisted for at least 5 years after implementation. We also find
      that data from judicial system administrative agency reports make an important
      contribution to public policy analysis. In the face of persistent antiregulatory
      forces and public-sector budget cuts, it is critically important to document the
      relationship between enforcement activities and the achievement of legislative
      goals.

PMID- 25569428
TI  - Cinnamon ameliorates experimental allergic encephalomyelitis in mice via
      regulatory T cells: implications for multiple sclerosis therapy.
AB  - Upregulation and/or maintenance of regulatory T cells (Tregs) during an
      autoimmune insult may have therapeutic efficacy in autoimmune diseases. Although
      several immunomodulatory drugs and molecules are available, most present
      significant side effects over long-term use. Cinnamon is a commonly used natural
      spice and flavoring material used for centuries throughout the world. Here, we
      have explored a novel use of cinnamon powder in protecting Tregs and treating the
      disease process of experimental allergic encephalomyelitis (EAE), an animal model
      of MS. Oral feeding of cinnamon (Cinnamonum verum) powder suppresses clinical
      symptoms of relapsing-remitting EAE in female PLP-TCR transgenic mice and
      adoptive transfer mouse model. Cinnamon also inhibited clinical symptoms of
      chronic EAE in male C57/BL6 mice. Dose-dependent study shows that cinnamon powder
      at a dose of 50 mg/kg body wt/d or higher significantly suppresses clinical
      symptoms of EAE in mice. Accordingly, oral administration of cinnamon also
      inhibited perivascular cuffing, maintained the integrity of blood-brain barrier
      and blood-spinal cord barrier, suppressed inflammation, normalized the expression
      of myelin genes, and blocked demyelination in the central nervous system of EAE
      mice. Interestingly, cinnamon treatment upregulated Tregs via reduction of nitric
      oxide production. Furthermore, we demonstrate that blocking of Tregs by
      neutralizing antibodies against CD25 abrogates cinnamon-mediated protection of
      EAE. Taken together, our results suggest that oral administration of cinnamon
      powder may be beneficial in MS patients and that no other existing anti-MS
      therapies could be so economical and trouble-free as this approach. 

PMID- 25569427
TI  - A new family of secreted toxins in pathogenic Neisseria species.
AB  - The genus Neisseria includes both commensal and pathogenic species which are
      genetically closely related. However, only meningococcus and gonococcus are
      important human pathogens. Very few toxins are known to be secreted by pathogenic
      Neisseria species. Recently, toxins secreted via type V secretion system and
      belonging to the widespread family of contact-dependent inhibition (CDI) toxins
      have been described in numerous species including meningococcus. In this study,
      we analyzed loci containing the maf genes in N. meningitidis and N. gonorrhoeae
      and proposed a novel uniform nomenclature for maf genomic islands (MGIs). We
      demonstrated that mafB genes encode secreted polymorphic toxins and that genes
      immediately downstream of mafB encode a specific immunity protein (MafI). We
      focused on a MafB toxin found in meningococcal strain NEM8013 and characterized
      its EndoU ribonuclease activity. maf genes represent 2% of the genome of
      pathogenic Neisseria, and are virtually absent from non-pathogenic species, thus
      arguing for an important biological role. Indeed, we showed that overexpression
      of one of the four MafB toxins of strain NEM8013 provides an advantage in
      competition assays, suggesting a role of maf loci in niche adaptation. 

PMID- 25569431
TI  - A compassionate complaint about hospital care made a difference.

PMID- 25569432
TI  - Improving serodiagnosis of human and canine leishmaniasis with recombinant
      Leishmania braziliensis cathepsin l-like protein and a synthetic peptide
      containing its linear B-cell epitope.
AB  - BACKGROUND: The early and correct diagnosis of human leishmaniasis is essential
      for disease treatment. Another important step in the control of visceral
      leishmaniasis is the identification of infected dogs, which are the main domestic
      reservoir of L. infantum. Recombinant proteins and synthetic peptides based on
      Leishmania genes have emerged as valuable targets for serodiagnosis due to their
      increased sensitivity, specificity and potential for standardization. Cathepsin L
      like genes are surface antigens that are secreted by amastigotes and have little
      similarity to host proteins, factors that enable this protein as a good target
      for serodiagnosis of the leishmaniasis. METHODOLOGY/PRINCIPAL FINDINGS: We mapped
      a linear B-cell epitope within the Cathepsin L-like protein from L. braziliensis.
      A synthetic peptide containing the epitope and the recombinant protein was
      evaluated for serodiagnosis of human tegumentary and visceral leishmaniasis, as
      well as canine visceral leishmaniasis. CONCLUSIONS/SIGNIFICANCE: The recombinant
      protein performed best for human tegumentary and canine visceral leishmaniasis,
      with 96.30% and 89.33% accuracy, respectively. The synthetic peptide was the best
      to discriminate human visceral leishmaniasis, with 97.14% specificity, 94.55%
      sensitivity and 96.00% accuracy. Comparison with T. cruzi-infected humans and
      dogs suggests that the identified epitope is specific to Leishmania parasites,
      which minimizes the likelihood of cross-reactions.

PMID- 25569433
TI  - Assessment of incidental findings in 232 whole-exome sequences from the Baylor
      Hopkins Center for Mendelian Genomics.
AB  - PURPOSE: In March 2013 the American College of Medical Genetics and Genomics
      published a list of 56 genes with the recommendation that pathogenic and likely
      pathogenic variants detected incidentally by clinical sequencing be reported to
      patients. As an initial step in determining the practical consequences of this
      recommendation in the research setting, we searched for variants in these genes
      in 232 whole-exome sequences from the Baylor-Hopkins Center for Mendelian
      Genomics. METHODS: We identified rare, nonsynonymous, and splicing single
      nucleotide variants and insertions/deletions and assessed variant classification
      using the Human Gene Mutation, Emory, and ClinVar databases. We analyzed the
      burden of mutation in each of the 56 genes and determined which variants should
      be reported to patients. RESULTS: Our filtering resulted in 249 distinct
      variants, with a mean of 1.69 variants per individual. Half of these were novel
      missense mutations not classified by any of the three reference databases. Of 101
      variants listed in the Human Gene Mutation Database, 48 were also in ClinVar and
      3 were also in Emory; half of these shared variants were classified discordantly
      between databases. Some genes consistently had greater variation than others. In
      total, 0.86% of individuals had a reportable incidental variant. CONCLUSION:
      These observations demonstrate some current challenges of assessing phenotypic
      consequences of incidental variants for counseling patients.

PMID- 25569434
TI  - Economic evaluation of genetic screening for Lynch syndrome in Germany.
AB  - PURPOSE: Lynch syndrome (LS) screening among patients with newly diagnosed
      colorectal cancer can decrease mortality in their affected first-degree
      relatives. In Germany, it is not yet clinical practice and the cost-effectiveness
      of different testing strategies is unknown. METHODS: We developed a decision
      analytic model to analyze the cost-effectiveness of LS screening from the
      perspective of the German Statutory Health Insurance system. A total of 22
      testing strategies considering family-history assessment, analysis of tumor
      samples (i.e., immunohistochemistry (IHC), microsatellite instability, and BRAF
      mutation testing) and genetic sequencing were analyzed. Life-years gained in
      relatives by closed-meshed colonoscopy and aspirin prophylaxis were estimated by
      Markov models. Uncertainty was assessed deterministically and probabilistically.
      RESULTS: On average, detected mutation carriers gained 0.52 life-years
      (undiscounted: 1.34) by increased prevention. Most strategies were dominated,
      with three exceptions: family assessment by the Bethesda criteria followed by IHC
      and BRAF testing and genetic sequencing; IHC and BRAF testing and genetic
      sequencing; and direct sequencing of all index patients. Their incremental cost
      effectiveness was [euro ]77,268, [euro ]253,258, and [euro ]4,188,036 per life
      year gained, respectively. CONCLUSION: The results were less favorable than those
      of previous models. Chemoprevention appears to provide comparably low additional
      benefit and improves cost-effectiveness only slightly.

PMID- 25569435
TI  - Practical guidelines for managing adults with 22q11.2 deletion syndrome.
AB  - 22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome
      in humans, estimated to affect up to 1 in 2,000 live births. Major features of
      this multisystem condition include congenital anomalies, developmental delay, and
      an array of early- and later-onset medical and psychiatric disorders. Advances in
      pediatric care ensure a growing population of adults with 22q11.2DS. Informed by
      an international panel of multidisciplinary experts and a comprehensive review of
      the existing literature concerning adults, we present the first set of guidelines
      focused on managing the neuropsychiatric, endocrine, cardiovascular,
      reproductive, psychosocial, genetic counseling, and other issues that are the
      focus of attention in adults with 22q11.2DS. We propose practical strategies for
      the recognition, evaluation, surveillance, and management of the associated
      morbidities.Genet Med 17 8, 599-609. 

PMID- 25569436
TI  - Identifying gene disruptions in novel balanced de novo constitutional
      translocations in childhood cancer patients by whole-genome sequencing.
AB  - PURPOSE: We applied whole-genome sequencing (WGS) to children diagnosed with
      neoplasms and found to carry apparently balanced constitutional translocations to
      discover novel genic disruptions. METHODS: We applied the structural variation
      (SV) calling programs CREST, BreakDancer, SV-STAT, and CGAP-CNV, and we developed
      an annotative filtering strategy to achieve nucleotide resolution at the
      translocations. RESULTS: We identified the breakpoints for t(6;12)(p21.1;q24.31),
      disrupting HNF1A in a patient diagnosed with hepatic adenomas and maturity-onset
      diabetes of the young (MODY). Translocation as the disruptive event of HNF1A, a
      gene known to be involved in MODY3, has not been previously reported. In a
      subject with Hodgkin lymphoma and subsequent low-grade glioma, we identified
      t(5;18)(q35.1;q21.2), disrupting both SLIT3 and DCC, genes previously implicated
      in both glioma and lymphoma. CONCLUSION: These examples suggest that implementing
      clinical WGS in the diagnostic workup of patients with novel but apparently
      balanced translocations may reveal unanticipated disruption of disease-associated
      genes and aid in prediction of the clinical phenotype.

PMID- 25569437
TI  - Identification of false-negative mutations missed by next-generation sequencing
      in retinitis pigmentosa patients: a complementary approach to clinical genetic
      diagnostic testing.
AB  - PURPOSE: Retinitis pigmentosa (RP) is a major cause of heritable human blindness
      with extreme genetic heterogeneity. A large number of causative genes have been
      defined by next-generation sequencing (NGS). However, due to technical
      limitations, determining the existence of uncovered or low-depth regions is a
      fundamental challenge in analyzing NGS data. Therefore, undetected mutations may
      exist in genomic regions less effectively covered by NGS. METHODS: To address
      this problem, we tested a complementary approach for identifying previously
      undetected mutations in NGS data sets. The strategy consisted of coverage-based
      analysis and additional target screening of low-depth regions. Fifty RP patients
      were analyzed, and none of the mutations found had previously been identified by
      NGS. RESULTS: Coverage-based analysis indicated that, because of a highly
      repetitive sequence, the RPGR open reading frame (ORF)15 was located in an
      uncovered or low-depth region. Through additional screening of ORF15, we
      identified pathogenic mutations in 14% (7/50) of patients, including four novel
      mutations first described herein. CONCLUSION: In brief, we support the need for a
      complementary approach to identify mutations undetected by NGS, underscoring the
      power and significance of combining coverage-based analysis with additional
      target screening of low-depth regions in improving diagnosis of genetic diseases.
      In addition to its usefulness in RP, this approach is likely applicable to other
      Mendelian diseases.

PMID- 25569438
TI  - Maternal cell-free DNA-based screening for fetal microdeletion and the importance
      of careful diagnostic follow-up.
AB  - BACKGROUND: Noninvasive prenatal screening (NIPS) by next-generation sequencing
      of cell-free DNA (cfDNA) in maternal plasma is used to screen for common
      aneuploidies such as trisomy 21 in high risk pregnancies. NIPS can identify fetal
      genomic microdeletions; however, sensitivity and specificity have not been
      systematically evaluated. Commercial companies have begun to offer expanded
      panels including screening for common microdeletion syndromes such as 22q11.2
      deletion (DiGeorge syndrome) without reporting the genomic coordinates or whether
      the deletion is maternal or fetal. Here we describe a phenotypically normal
      mother and fetus who tested positive for atypical 22q deletion via maternal
      plasma cfDNA testing. METHODS: We performed cfDNA sequencing on saved maternal
      plasma obtained at 11 weeks of gestation from a phenotypically normal woman with
      a singleton pregnancy whose earlier screening at a commercial laboratory was
      reported to be positive for a 22q11.2 microdeletion. Fluorescence in situ
      hybridization and chromosomal microarray diagnostic genetic tests were done
      postnatally. CONCLUSION: NIPS detected a 22q microdeletion that, upon diagnostic
      workup, did not include the DiGeorge critical region. Diagnostic prenatal or
      postnatal testing with chromosomal microarray and appropriate parental studies to
      determine precise genomic coordinates and inheritance should follow a positive
      microdeletion NIPS result.

PMID- 25569439
TI  - A preliminary investigation of genetic counselors' information needs when
      receiving a variant of uncertain significance result: a mixed methods study.
AB  - PURPOSE: The aim of this study was to explore genetic counselors' information
      preferences on reports of variant of uncertain significance (VUS) results from
      cancer genetic testing. METHODS: This mixed methods report (quantitative and
      qualitative approaches) utilized a survey of genetic counselors containing closed
      and open-ended questions to explore genetic counselors' information needs and
      perceptions of the industry's current information sharing practices. Descriptive
      statistics were calculated for responses to the closed-ended questions, and
      thematic analysis guided the interpretation of the open-ended questions. RESULTS:
      Of the 267 participants (28.6% response rate), the majority indicated a perceived
      lack of information on VUS laboratory reports, were concerned about the perceived
      practice of withholding information, and stated the information they wanted to
      see. Although most did not indicate how additional information would be used,
      some reported they would provide information directly to patients, and others
      reported that the information would be used to contextualize the VUS result when
      counseling patients. CONCLUSION: This analysis identified information that
      genetic counselors believe is needed in VUS reports, indicating what they believe
      are best practices in lieu of guidelines for laboratories currently providing
      genetic testing services. Future studies should explore how genetic counselors
      use additional information contained in VUS reports.Genet Med 17 9, 739-746.

PMID- 25569442
TI  - The Impact of Dietary Interventions on the Symptoms of Inflammatory Bowel
      Disease: A Systematic Review.
AB  - Diet may be a successful part of the treatment plan for improving outcome in
      patients with inflammatory bowel disease (IBD). This study aimed to
      systematically review all published clinical trials evaluating the effects of a
      regular diet on symptoms of IBD. Three medical databases were searched for
      clinical trials evaluating an intervention that involved dietary manipulation
      using a regular diet on adults with IBD whose symptoms were objectively measured
      before and after the intervention. The most common types of regular diet
      interventions that we observed in the literature fell into the following three
      categories: low residue/low fiber diets, exclusion diets, or other specific
      diets. Of all included studies, the few that were of higher quality and that
      observed a statistically significant improvement in symptoms in the diet group
      compared to the control group fell under the exclusion diet group or the other
      specific diet group. We were able to identify several high quality clinical
      trials evaluating dietary manipulations on symptoms of IBD. Exclusion diets and
      the low FODMAP diet are two areas identified in this review that show promise for
      having therapeutic benefits for patients with IBD. 

PMID- 25569440
TI  - Small-scale high-throughput sequencing-based identification of new therapeutic
      tools in cystic fibrosis.
AB  - PURPOSE: Although 97-99% of CFTR mutations have been identified, great efforts
      must be made to detect yet-unidentified mutations. METHODS: We developed a small
      scale next-generation sequencing approach for reliably and quickly scanning the
      entire gene, including noncoding regions, to identify new mutations. We applied
      this approach to 18 samples from patients suffering from cystic fibrosis (CF) in
      whom only one mutation had hitherto been identified. RESULTS: Using an in-house
      bioinformatics pipeline, we could rapidly identify a second disease-causing CFTR
      mutation for 16 of 18 samples. Of them, c.1680-883A>G was found in three
      unrelated CF patients. Analysis of minigenes and patients' transcripts showed
      that this mutation results in aberrantly spliced transcripts because of the
      inclusion of a pseudoexon. It is located only three base pairs from the c.1680
      886A>G mutation (1811+1.6kbA>G), the fourth most frequent mutation in
      southwestern Europe. We next tested the effect of antisense oligonucleotides
      targeting splice sites on these two mutations on pseudoexon skipping.
      Oligonucleotide transfection resulted in the restoration of the full-length, in
      frame CFTR transcript, demonstrating the effect of antisense oligonucleotide
      induced pseudoexon skipping in CF. CONCLUSION: Our data confirm the importance of
      analyzing noncoding regions to find unidentified mutations, which is essential to
      designing targeted therapeutic approaches.

PMID- 25569441
TI  - Implications of polygenic risk-stratified screening for prostate cancer on
      overdiagnosis.
AB  - PURPOSE: This study aimed to quantify the probability of overdiagnosis of
      prostate cancer by polygenic risk. METHODS: We calculated the polygenic risk
      score based on 66 known prostate cancer susceptibility variants for 17,012 men
      aged 50-69 years (9,404 men identified with prostate cancer and 7,608 with no
      cancer) derived from three UK-based ongoing studies. We derived the probabilities
      of overdiagnosis by quartiles of polygenic risk considering that the observed
      prevalence of screen-detected prostate cancer is a combination of underlying
      incidence, mean sojourn time (MST), test sensitivity, and overdiagnosis. RESULTS:
      Polygenic risk quartiles 1 to 4 comprised 9, 18, 25, and 48% of the cases,
      respectively. For a prostate-specific antigen test sensitivity of 80% and MST of
      9 years, 43, 30, 25, and 19% of the prevalent screen-detected cancers in
      quartiles 1 to 4, respectively, were likely to be overdiagnosed cancers.
      Overdiagnosis decreased with increasing polygenic risk, with 56% decrease between
      the lowest and the highest polygenic risk quartiles. CONCLUSION: Targeting
      screening to men at higher polygenic risk could reduce the problem of
      overdiagnosis and lead to a better benefit-to-harm balance in screening for
      prostate cancer.

PMID- 25569443
TI  - Public health insurance and disparate eligibility of spouses: The Medicare
      eligibility gap.
AB  - I exploit the age-based eligibility structure of Medicare and the age gap between
      spouses to examine the impact of Medicare eligibility of an older spouse on the
      insurance coverage of younger, Medicare-ineligible spouses. Using a regression
      discontinuity framework, I find that Medicare eligibility of an older spouse can
      crowd-out the health insurance coverage of a younger spouse. Medicare eligibility
      of older wives increases the likelihood that younger husbands are uninsured.
      Younger wives are less likely to be covered through an employer-based plan and
      more likely to have non-group coverage after an older husband turns 65. 

PMID- 25569445
TI  - Orientation selectivity in inhibition-dominated networks of spiking neurons:
      effect of single neuron properties and network dynamics.
AB  - The neuronal mechanisms underlying the emergence of orientation selectivity in
      the primary visual cortex of mammals are still elusive. In rodents, visual
      neurons show highly selective responses to oriented stimuli, but neighboring
      neurons do not necessarily have similar preferences. Instead of a smooth map, one
      observes a salt-and-pepper organization of orientation selectivity. Modeling
      studies have recently confirmed that balanced random networks are indeed capable
      of amplifying weakly tuned inputs and generating highly selective output
      responses, even in absence of feature-selective recurrent connectivity. Here we
      seek to elucidate the neuronal mechanisms underlying this phenomenon by resorting
      to networks of integrate-and-fire neurons, which are amenable to analytic
      treatment. Specifically, in networks of perfect integrate-and-fire neurons, we
      observe that highly selective and contrast invariant output responses emerge,
      very similar to networks of leaky integrate-and-fire neurons. We then demonstrate
      that a theory based on mean firing rates and the detailed network topology
      predicts the output responses, and explains the mechanisms underlying the
      suppression of the common-mode, amplification of modulation, and contrast
      invariance. Increasing inhibition dominance in our networks makes the rectifying
      nonlinearity more prominent, which in turn adds some distortions to the otherwise
      essentially linear prediction. An extension of the linear theory can account for
      all the distortions, enabling us to compute the exact shape of every individual
      tuning curve in our networks. We show that this simple form of nonlinearity adds
      two important properties to orientation selectivity in the network, namely
      sharpening of tuning curves and extra suppression of the modulation. The theory
      can be further extended to account for the nonlinearity of the leaky model by
      replacing the rectifier by the appropriate smooth input-output transfer function.
      These results are robust and do not depend on the state of network dynamics, and
      hold equally well for mean-driven and fluctuation-driven regimes of activity. 

PMID- 25569446
TI  - Heck cyclization strategy for preparation of erythrinan alkaloids: asymmetric
      synthesis of unnatural (-)-erysotramidine from L-tartaric acid.
AB  - With an imide derived from L-tartaric acid as the starting material, ent
      erysotramidine was synthesized for the first time. The synthesis features the use
      of the enantiopure synthon, prepared in a set of highly stereoselective
      reactions, including N-acyliminium cyclization, dihydrofuranyl ring formation via
      silver-catalyzed intramolecular alcohol addition to acetylene, and vinyl ether
      catalytic hydrogen reduction. The crucial step of the synthesis, assembly of ring
      A, was achieved by using Heck cyclization of (Z)-iodoolefin.

PMID- 25569448
TI  - Blockade of the Ras/Raf/ERK and Ras/PI3K/Akt Pathways by Monacolin K Reduces the
      Expression of GLO1 and Induces Apoptosis in U937 Cells.
AB  - Monacolin K, a hydrolytic product of icaritin, is the major active component in
      the traditional fermented Monascus purpureus. Monacolin K inhibits the
      proliferation of acute myeloid leukemia (AML), but underlying mechanisms remain
      to be identified. The present study demonstrates that monacolin K inhibits the
      proliferation of human AML cell line U937 in a dose-dependent manner.
      Importantly, morphological, DNA fragmentation, and image cytometry analyses
      indicated that monacolin K induced U937 cell apoptosis. Monacolin K could
      inactivate Ras translocation from cytosol to cell membrane. Monacolin K could
      also reduce the Ras-dependent phosphorylation of ERK and Akt, and the subsequent
      translocation of nuclear factor kappa B (NF-kappaB) from cytosol to nucleus in
      U937 cells. The underlying mechanisms of apoptotic activity of monacolin K were
      associated with inhibition of the Ras/Raf/ERK and Ras/PI3K/Akt signals and down
      regulation of HMG-CoA reductase and glyoxalase 1. On the basis of results
      obtained using specific inhibitors U0126, LY294002, and JSH-23, the
      Ras/Raf/ERK/NF-kappaB/GLO1 and Ras/Akt/NF-kappaB/GLO1 pathways were proposed for
      the apoptotic effect of monacolin K in U937 cells.

PMID- 25569447
TI  - Evaluation of sunlight induced structural changes and their effect on the
      photocatalytic activity of V2O5 for the degradation of phenols.
AB  - Despite knowing the fact that vanadium pentoxide is slightly soluble in aqueous
      medium, its photocatalytic activity was evaluated for the degradation of phenol
      and its derivatives (2-hydroxyphenol, 2-chlorophenol, 2-aminophenol and 2
      nitrophenol) in natural sunlight exposure. The prime objective of the study was
      to differentiate between the homogeneous and heterogeneous photocatalysis
      incurred by dissolved and undissolved V2O5 in natural sunlight exposure. V2O5 was
      synthesized by chemical precipitation procedure using Triton X-100 as morphology
      mediator and characterized by DRS, PLS, Raman, FESEM and XRD. A lower solubility
      of ~ 5% per 100ml of water at 23  degrees C was observed after calcination at 600
      degrees C. The study revealed no contribution of the dissolved V2O5 in the
      photocatalytic process. In sunlight exposure, V2O5 powder exhibited substantial
      activity for the degradation, however, a low mineralization of phenolic
      substrates was observed. The initial low activity of V2O5 followed by a sharp
      increase both in degradation and mineralization in complete spectrum sunlight
      exposure, was further investigated that revealed the decrease in the bandgap and
      the reduction in the particle size with the interaction of UV photons (<420 nm)
      as this effect was not observable in the exposure of visible region of sunlight.
      The role of the chemically different substituents attached to an aromatic ring at
      2-positions and the secondary interaction of released ions during the degradation
      process with the reactive oxygen species (ROS) was also explored.

PMID- 25569449
TI  - Waits for emergency care are worst for 10 years, figures show.

PMID- 25569450
TI  - Fusobacterium nucleatum: an emerging bug in colorectal tumorigenesis.
AB  - The human intestinal microbiota is a plethora of diverse microbial species,
      wherein certain bacteria considered as driver bacteria with procarcinogenic
      features contribute directly toward colonic epithelium cell damage to initiate
      colorectal carcinogenesis. However, some bacteria, in particular Fusobacterium
      nucleatum, which is otherwise a normal resident of the oral microflora and a
      relatively poor colonizer of the healthy gut, have also been considered to play a
      role in the development of colorectal cancer. Many studies have reported that F.
      nucleatum is associated with colorectal adenomas and advanced-stage colorectal
      cancer, but its precise role in the early stages of colorectal tumorigenesis is
      poorly understood. Here, we review some of the important features of F.
      nucleatum, its association with inflammatory bowel disease, modulation of the
      tumor-immune microenvironment, and E-cadherin/beta-catenin signaling. 

PMID- 25569451
TI  - The relationship between education level and mammographic density.
AB  - To further understand the factors that contribute to interindividual variation in
      mammographic density, we evaluated the relationship between education level and
      each component of the mammographic density measures. Study participants included
      535 women between 40 and 65 years of age who received a mammogram for a
      population-based twin and family study. Mammographic density was measured from
      digital mammograms using a computer-assisted thresholding method. To avoid
      negative confounding by obesity level, we calculated BMI-adjusted mammographic
      measures. Thereafter, each of the mammographic density measures was t-transformed
      using its mean value and SD for each age strata. The level of education was
      chosen as a marker representing socioeconomic status at the individual level. A
      linear mixed model considering familial correlations was used for analyses. In
      the unadjusted analysis for all women, the BMI-adjusted nondense area gradually
      decreased with an increase in education level (P for trend=0.017). This
      association persisted after adjusting for menstrual and reproductive factors.
      When we repeated the analysis according to menopausal status, an inverse
      association between education level and nondense area was evident in
      premenopausal women, whereas the inverse association attenuated to a
      statistically insignificant level after adjusting for menstrual and reproductive
      factors in postmenopausal women. Absolute dense area and percentage dense area
      were not associated with education level. The significant association between
      nondense area and education level after eliminating the effect of age and BMI
      suggests that socioeconomic factors may have an influential role in determining
      the amount of fat tissue in the breast. 

PMID- 25569452
TI  - Maternal and birth anthropometric characteristics in relation to the risk of
      childhood lymphomas: a Swedish nationwide cohort study.
AB  - This Swedish nationwide cohort study aims to examine the role of maternal
      characteristics (maternal age, education, smoking, BMI, diabetes, and
      preeclampsia) and multiple intrauterine growth measures on the risk of childhood
      lymphomas. A total of 3 444 136 singleton live births registered in the Swedish
      Medical Birth Register were analyzed, among whom there were 515 incident non
      Hodgkin lymphoma (NHL) cases and 169 Hodgkin lymphoma (HL) cases aged 0-14 years
      at diagnosis (1973-2007) identified through linkage with the Swedish Cancer
      Register. Proportional hazards models were used to estimate the hazard ratio (HR)
      and 95% confidence intervals (95% CI) of NHL and HL. Male sex (HR=2.00, 95% CI:
      1.66-2.41), older maternal age (HR=1.03, 95% CI: 1.00-1.06, per 1-year increase),
      and large for gestational age compared with appropriate for gestational age (AGA)
      birth weight (HR=1.83, 95% CI: 1.20-2.79) were correlated with the risk of NHL;
      of note, in subanalysis by sex, the latter association was confined to girls
      (HR=3.37, 95% CI: 1.90-5.97, Pinteraction by sex=0.008). The risk of childhood HL
      overall was more evident among boys (HR=2.03, 95% CI: 1.46-2.81), whereas indices
      of accelerated fetal growth were not convincingly associated with the risk of HL.
      Apart from the established association with sex, the findings point to
      accelerated intrauterine growth as a risk factor for childhood NHL that may
      differ by sex. Given the rarity of this condition at birth, however, further
      studies with more elaborate indices are needed to conclude on its association
      with rare diseases such as HL. 

PMID- 25569453
TI  - Photoluminescent graphene quantum dots for in vivo imaging of apoptotic cells.
AB  - Apoptosis (programmed cell death) is linked to many incurable neurodegenerative,
      cardiovascular and cancer causing diseases. Numerous methods have been developed
      for imaging apoptotic cells in vitro; however, there are few methods available
      for imaging apoptotic cells in live animals (in vivo). Here we report a novel
      method utilizing the unique photoluminescence properties of plant leaf-derived
      graphene quantum dots (GQDs) modified with annexin V antibody (AbA5) to form
      (AbA5)-modified GQDs (AbA5-GQDs) enabling us to label apoptotic cells in live
      zebrafish (Danio rerio). The key is that zebrafish shows bright red
      photoluminescence in the presence of apoptotic cells. The toxicity of the GQDs
      has also been investigated with the GQDs exhibiting high biocompatibility as they
      were excreted from the zebrafish's body without affecting its growth
      significantly at a concentration lower than 2 mg mL(-1) over a period of 4 to 72
      hour post fertilization. The GQDs have further been used to image human breast
      adenocarcinoma cell line (MCF-7 cells), human cervical cancer cell line (HeLa
      cells), and normal human mammary epithelial cell line (MCF-10A). These results
      are indispensable to further the advance of graphene-based nanomaterials for
      biomedical applications. 

PMID- 25569444
TI  - Transmitted virus fitness and host T cell responses collectively define divergent
      infection outcomes in two HIV-1 recipients.
AB  - Control of virus replication in HIV-1 infection is critical to delaying disease
      progression. While cellular immune responses are a key determinant of control,
      relatively little is known about the contribution of the infecting virus to this
      process. To gain insight into this interplay between virus and host in viral
      control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A
      transmission pairs in which female recipients sharing three HLA class I alleles
      exhibited contrasting clinical outcomes: R880F controlled virus replication while
      R463F experienced high viral loads and rapid disease progression. Near full
      length single genome amplification defined the infecting transmitted/founder
      (T/F) virus proteome and subsequent sequence evolution over the first year of
      infection for both acutely infected recipients. T/F virus replicative capacities
      were compared in vitro, while the development of the earliest cellular immune
      response was defined using autologous virus sequence-based peptides. The R880F
      T/F virus replicated significantly slower in vitro than that transmitted to
      R463F. While neutralizing antibody responses were similar in both subjects,
      during acute infection R880F mounted a broad T cell response, the most dominant
      components of which targeted epitopes from which escape was limited. In contrast,
      the primary HIV-specific T cell response in R463F was focused on just two
      epitopes, one of which rapidly escaped. This comprehensive study highlights both
      the importance of the contribution of the lower replication capacity of the
      transmitted/founder virus and an associated induction of a broad primary HIV
      specific T cell response, which was not undermined by rapid epitope escape, to
      long-term viral control in HIV-1 infection. It underscores the importance of the
      earliest CD8 T cell response targeting regions of the virus proteome that cannot
      mutate without a high fitness cost, further emphasizing the need for vaccines
      that elicit a breadth of T cell responses to conserved viral epitopes. 

PMID- 25569454
TI  - Baculoviruses and nucleosome management.
AB  - Negatively-supercoiled-ds DNA molecules, including the genomes of baculoviruses,
      spontaneously wrap around cores of histones to form nucleosomes when present
      within eukaryotic nuclei. Hence, nucleosome management should be essential for
      baculovirus genome replication and temporal regulation of transcription, but this
      has not been documented. Nucleosome mobilization is the dominion of ATP-dependent
      chromatin-remodeling complexes. SWI/SNF and INO80, two of the best-studied
      complexes, as well as chromatin modifier TIP60, all contain actin as a subunit.
      Retrospective analysis of results of AcMNPV time course experiments wherein actin
      polymerization was blocked by cytochalasin D drug treatment implicate actin
      containing chromatin modifying complexes in decatenating baculovirus genomes,
      shutting down host transcription, and regulating late and very late phases of
      viral transcription. Moreover, virus-mediated nuclear localization of actin early
      during infection may contribute to nucleosome management. 

PMID- 25569456
TI  - Characterization of an H9N2 avian influenza virus from a Fringilla montifringilla
      brambling in northern China.
AB  - Avian H9N2 influenza viruses circulating in domestic poultry populations are
      occasionally transmitted to humans. We report the genomic characterization of an
      H9N2 avian influenza virus (A/Brambling/Beijing/16/2012) first isolated from a
      healthy Fringilla montifringilla brambling in northern China in 2012.
      Phylogenetic analyses revealed that this H9N2 virus belongs to the BJ/94-like
      sublineage. This virus had a low pathogenicity for chickens and was able to
      replicate at a low level in mouse lung tissue. Transmission studies in ferrets
      showed that this H9N2 strain shed high levels of the virus in nasal and throat
      swabs. In vitro receptor binding assays, the virus bound only to alpha-2,6
      linkage receptors and not to the avian-type alpha-2,3 linkage receptors,
      suggesting that H9N2 influenza viruses present potential public health risks.
      Therefore, attention should be paid to H9N2 influenza viruses and the close
      surveillance of H9N2 viruses in poultry. 

PMID- 25569457
TI  - Three-dimensional visualization of the Autographa californica multiple
      nucleopolyhedrovirus occlusion-derived virion envelopment process gives new clues
      as to its mechanism.
AB  - Baculoviruses produce two virion phenotypes, occlusion-derived virion (ODV) and
      budded virion (BV). ODV envelopment occurs in the nucleus. Morphogenesis of the
      ODV has been studied extensively; however, the mechanisms underlying microvesicle
      formation and ODV envelopment in nuclei remain unclear. In this study, we used
      electron tomography (ET) together with the conventional electron microscopy to
      study the envelopment of Autographa californica multiple nucleopolyhedrovirus
      (AcMNPV) ODV. Our results demonstrate that not only the inner but also the outer
      nuclear membrane can invaginate and vesiculate into microvesicles and that
      intranuclear microvesicles are the direct source of the ODV membrane. Five main
      events in the ODV envelopment process are summarized, from which we propose a
      model to explain this process. 

PMID- 25569458
TI  - National health and nutrition examination survey: sample design, 2011-2014.
AB  - Background Data collection for the National Health and Nutrition Examination
      Survey (NHANES) consists of a household screener, an interview, and a physical
      examination. The screener primarily determines whether any household members are
      eligible for the interview and examination. Eligibility is established using
      preset selection probabilities for the desired demographic subdomains. After an
      eligible sample person is selected, the interview collects person-level
      demographic, health, and nutrition information, as well as information about the
      household. The examination includes physical measurements, tests such as hearing
      and dental examinations, and the collection of blood and urine specimens for
      laboratory testing. Objectives This report provides some background on the NHANES
      program, beginning with the first survey cycle in the 1970s and highlighting
      significant changes since its inception. The report then describes the broad
      design specifications for the 2011-2014 survey cycle, including survey
      objectives, domain and precision specifications, and operational requirements
      unique to NHANES. The report also describes details of the survey design,
      including the calculation of sampling rates and sample selection methods.
      Documentation of survey content, data collection procedures, estimation methods,
      and methods to assess nonsampling errors are reported elsewhere. 

PMID- 25569459
TI  - Integrated microfluidic capillary electrophoresis-electrospray ionization devices
      with online MS detection for the separation and characterization of intact
      monoclonal antibody variants.
AB  - Here, we demonstrate an integrated microfluidic capillary electrophoresis
      electrospray ionization (CE-ESI) device for the separation of intact monoclonal
      antibody charge variants with online mass spectrometric (MS) identification. The
      need for dynamic coating and zwitterionic background electrolyte (BGE) additives
      has been eliminated by utilizing surface chemistry within the device channels to
      control analyte adsorption and electroosmotic flow (EOF) while maintaining
      separation efficiency. The effectiveness of this strategy was illustrated with
      the separation of charge variants of Infliximab. Three major species
      corresponding to C-terminal lysine variants were separated with an average
      resolution of 0.80 and identified by mass difference. In addition to the lysine
      variants, masses were determined for minor acidic and basic species. The
      separation of these variants prior to MS analysis facilitated the identification
      of glycosylation patterns for each of the variants. The general applicability of
      this method was demonstrated by analyzing two additional monoclonal antibody
      species: an IgG2 antibody and an IgG1 antibody conjugate. The IgG2 proved to have
      similar modifications to Infliximab with lower relative abundances of the lysine
      variants. Analysis of the IgG1 drug conjugate further exemplified the advantages
      of MS detection; differences in the extent of antibody conjugation were
      detectable despite limited CE resolution. The CE-ESI-MS methodology described
      here is a rapid and generic strategy for the separation of intact mAb charge
      variants and facilitates the identification of variants through MS detection. 

PMID- 25569455
TI  - Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1
      p30(II) accessory protein and the induction of oncogenic cellular transformation
      by p30(II)/c-MYC.
AB  - The human T-cell leukemia retrovirus type-1 (HTLV-1) p30(II) protein is a
      multifunctional latency-maintenance factor that negatively regulates viral gene
      expression and deregulates host signaling pathways involved in aberrant T-cell
      growth and proliferation. We have previously demonstrated that p30(II) interacts
      with the c-MYC oncoprotein and enhances c-MYC-dependent transcriptional and
      oncogenic functions. However, the molecular and biochemical events that mediate
      the cooperation between p30(II) and c-MYC remain to be completely understood.
      Herein we demonstrate that p30(II) induces lysine-acetylation of the c-MYC
      oncoprotein. Acetylation-defective c-MYC Lys->Arg substitution mutants are
      impaired for oncogenic transformation with p30(II) in c-myc(-/-) HO15.19
      fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further
      demonstrate that p30(II) is present in c-MYC-containing nucleoprotein complexes
      in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30(II) inhibits apoptosis
      in proliferating cells expressing c-MYC under conditions of genotoxic stress.
      These findings suggest that c-MYC-acetylation is required for the cooperation
      between p30(II)/c-MYC which could promote proviral replication and contribute to
      HTLV-1-induced carcinogenesis. 

PMID- 25569460
TI  - Novel route of toxicant exposure in an ancient extant vertebrate: nickel uptake
      by hagfish skin and the modifying effects of slime.
AB  - Utilizing an in vitro technique, the skin of Pacific hagfish (Eptatretus stouti)
      was shown to take up nickel from the water via a high affinity, low capacity
      transport pathway. Uptake was biphasic, with saturation occurring at low nickel
      exposure concentrations, superseded by linear, diffusive uptake at levels greater
      than 50 MUM. In vivo exposures showed that nickel accumulated mainly in the gill,
      heart, and brain, representing a tissue distribution distinct from that found in
      teleosts. Slime on the epidermal surface was shown to significantly reduce the
      uptake of low concentrations (10 MUM) of the metals zinc and nickel, but slime
      had no effect on organic nutrient (the amino acid l-alanine) absorption. At a
      higher metal exposure concentration (1 mM), slime was no longer protective,
      indicating saturation of metal-binding sites. This is the first study to show
      that metals can be taken up by the integument of hagfish. The ability of the skin
      to act as a transport epithelium may be of particular importance for a burrowing,
      benthic scavenger, such as hagfish, which are likely to be exposed to relatively
      enriched levels of metal toxicants through their habitat and lifestyle, and this
      may have consequences for human health through hagfish consumption. 

PMID- 25569461
TI  - Impact of surfactants on the crystallization of aqueous suspensions of celecoxib
      amorphous solid dispersion spray dried particles.
AB  - Amorphous solid dispersions are frequently prepared by spray drying. It is
      important that the resultant spray dried particles do not crystallize during
      formulation, storage, and upon administration. The goal of the current study was
      to evaluate the impact of surfactants on the crystallization of celecoxib
      amorphous solid dispersions (ASD), suspended in aqueous media. Solid dispersions
      of celecoxib with hydroxypropylmethylcellulose acetate succinate were
      manufactured by spray drying, and aqueous suspensions were prepared by adding the
      particles to acidified media containing various surfactants. Nucleation induction
      times were evaluated for celecoxib in the presence and absence of surfactants.
      The impact of the surfactants on drug and polymer leaching from the solid
      dispersion particles was also evaluated. Sodium dodecyl sulfate and Polysorbate
      80 were found to promote crystallization from the ASD suspensions, while other
      surfactants including sodium taurocholate and Triton X100 were found to inhibit
      crystallization. The promotion or inhibition of crystallization was found to be
      related to the impact of the surfactant on the nucleation behavior of celecoxib,
      as well as the tendency to promote leaching of the drug from the ASD particle
      into the suspending medium. It was concluded that surfactant choice is critical
      to avoid failure of amorphous solid dispersions through crystallization of the
      drug. 

PMID- 25569462
TI  - Detection of hazardous gas using multidemensional porous iron oxide nanorods
      decorated carbon nanoparticles.
AB  - Multidimensional porous iron oxide (Fe2O3) nanorods-decorated carbon
      nanoparticles (MPFCNPs) were fabricated using a dual-nozzle electrospray, thermal
      stirring, and heat treatment. Polypyrrole (PPy) NPs with FeOOH nanorods were
      synthesized by electrospraying Fe(3+) ions, which were adsorbed on the PPy NP
      surface; the adsorbed Fe(3+) ions reacted with NaOH to create FeOOH nuclei, and
      then followed thermal stirring grow nanorods without aggregation. MPFCNPs were
      fabricated through heat treatment, with the porous structure created in the Fe2O3
      nanorods by hydroxyl group decomposition. The size of the MPFCNPs and the length
      of the porous Fe2O3 nanorods were controlled by the PPy NP template and
      concentration of initiator solution, respectively. The MPFCNPs were then utilized
      as a chemical sensor transducer for NO2 gas detection at room temperature. The
      response of the MFPCNP sensor was highly sensitive, displaying a minimum
      detectable level of 1 ppm; this detection level is lower than that of organic
      inorganic hybrid sensors. Moreover, sensitivity also improved with decreasing the
      diameter of MPFCNPs and increasing Fe2O3 nanorod length. The enhanced sensitivity
      was attributed to the larger surface area presented by the particle size and the
      porous structure. 

PMID- 25569463
TI  - [ENT surgery in anticoagulate patients].
AB  - BACKGROUND: In elective ENT surgery, one frequently sees -patients on oral
      anticoagulants and platelet inhibitors. While continuation of these therapies
      increases the risk of bleeding complications, indiscriminate discontinuation can
      have severe thromboembolic consequences. Furthermore, the number of 
      anticoagulants and platelet inhibitors in use has increased. The ENT-specialist
      is regulary confronted with the question of continuation, discontinuation, or
      bridging of this therapy. METHODS: Review of the available literature on bleeding
      complications associated with ENT interventions performed with and without
      anticoagulants. Overview of the indications for anticoagulants and the different
      mechansims of action and properties of the different agents. Development of
      protocols for risk stratification and for perioperative management. CONCLUSIONS:
      Patients on oral anticoagulants and platelet inhibitors have significant
      morbidity and mortality not only due to the underlying diseases, but also due to
      the perioperative management of these therapies. Perioperative management should
      be based on well-established treatment guidelines or, in high-risk patients, on
      multidisciplinary consultation. Even though the recommendations here are evidence
      based and cover a multitude of clinical contingencies, they cannot replace
      clinical decision making, which must consider the specific characteristics and
      circumstances of the patient, the planned intervention, and the surgical
      environment.

PMID- 25569464
TI  - [Deafness, blindness, ataxia].

PMID- 25569465
TI  - [From the expert's office: When is a hearing loss in the high tone range with
      coexisting hearing loss in all frequencies consequence of professional noise
      exposure? Frequent false evaluation of consultants, consulting physicians and
      professional unions].

PMID- 25569466
TI  - [Somnology - what is of importance for the ENT-specialist? An overview on the
      current guidelines in sleep medicine].
AB  - The somnology occupies a firm place in medical care of the ENT physician. The S3
      guideline "non-restorative sleep/sleep" defines the standards in diagnosis and
      therapy. Among the sleep-disordered breathing obstructive sleep apnea syndrome is
      the most common sleep breathing disorder among those aged 30-60 years. The
      diagnostics is based on a stepwise approach by ambulatory polygraphy and
      subsequent inpatient polysomnography. Depending on the focus degree of OSA and
      symptoms of the patient various treatment options surgical and conservative for
      the ENT specialist are available today. The superior form of therapy for all
      severities of OSA remains the non-invasive nocturnal airway pressure (CPAP).
      Detailed knowledge of sleep medicine is essential for differential diagnosis and
      the correct treatment decision. An interdisciplinary collaboration with a
      neurologist, pediatrician or pulmonologist should be included in more complex
      cases. 

PMID- 25569467
TI  - [Preoperative checklist - 2].

PMID- 25569468
TI  - Doctors increasingly practise "defensive" medicine for fear of litigation, says
      regulator.

PMID- 25569469
TI  - Methodology of electrical impedance tomography-derived measures of regional lung
      ventilation.

PMID- 25569470
TI  - Early inpatient rehabilitation admission and stroke patient outcomes.
AB  - OBJECTIVE: The aim of this study was to examine the associations of onset days,
      time from stroke onset to inpatient rehabilitation facility (IRF) admission, and
      patient outcomes (FIM gain, discharge destination, and IRF length of stay), using
      nationally representative data. DESIGN: A secondary data analysis was conducted
      on a random sample of stroke patients discharged from IRFs in the United States
      between 2009 and 2011, including mildly (n = 649), moderately (n = 2185), and
      severely (n = 2390) impaired patients. RESULTS: The study sample had a median of
      onset days of 5.5, with an interquartile range of 4-9. With the use of 15-365
      days as reference, the severely impaired patients had a higher cognition gain (P
      < 0.01) and were more likely to be discharged to the community (odds ratio, 1.45;
      95% confidence interval, 1.12-1.87) when admitted within 7 days, a greater motor
      gain when admitted within 14 days (P < 0.01), and a lower risk for acute hospital
      transfer when admitted 3-7 days (odds ratio, 0.62; 95% confidence interval, 0.43
      0.90). The moderately impaired patients had a greater motor gain when admitted
      within 7 days (P < 0.01). Early IRF admission was also associated with a shorter
      length of stay. CONCLUSIONS: Earlier IRF admission was beneficial among severely
      and moderately impaired patients. IRF admission within 7 days is recommended for
      stroke patients who achieved medical stability.

PMID- 25569471
TI  - Mendel, molecular biology, and apolipoprotein C-III: a heady combination.

PMID- 25569472
TI  - Aerosol-assisted chemical vapor deposition of tungsten oxide films and nanorods
      from oxo tungsten(VI) fluoroalkoxide precursors.
AB  - Aerosol-assisted chemical vapor deposition (AACVD) of WOx was demonstrated using
      the oxo tungsten(VI) fluoroalkoxide single-source precursors, WO[OCCH3(CF3)2]4
      and WO[OC(CH3)2CF3]4. Substoichiometric amorphous tungsten oxide thin films were
      grown on indium tin oxide (ITO) substrates in nitrogen at low deposition
      temperature (100-250  degrees C). At growth temperatures above 300  degrees C,
      the W18O49 monoclinic crystalline phase was observed. The surface morphology and
      roughness, visible light transmittance, electrical conductivity, and work
      function of the tungsten oxide materials are reported. The solvent and carrier
      gas minimally affected surface morphology and composition at low deposition
      temperature; however, material crystallinity varied with solvent choice at higher
      temperatures. The work function of the tungsten oxide thin films grown between
      150 and 250  degrees C was determined to be in the range 5.0 to 5.7 eV, according
      to ultraviolet photoelectron spectroscopy (UPS). 

PMID- 25569473
TI  - Does MAP2 have a role in predicting the development of anti-NMDAR encephalitis
      associated with benign ovarian teratoma? A report of six new pediatric cases.
AB  - Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a potentially
      fatal neurologic syndrome in which patients present with a spectrum of central
      nervous system deficits. Sixty percent of the cases can be attributed to the
      presence of tumors, most often ovarian teratomas. This report examines 6
      pediatric patients who presented with neurologic deficits associated with the
      presence of such tumors. These cases illustrate a perplexing phenomenon, where
      benign teratomas could have a possible association with anti-NMDAR encephalitis.
      The purpose of this study was to compare the histology and immunohistochemistry
      of tumors associated with this syndrome to ovarian teratomas found in patients
      presenting with no neurologic symptoms. After obtaining institutional review
      board approval, 57 cases of ovarian teratomas were identified at our institution
      over 12 years. Six patients were identified with anti-NMDAR encephalitis. A panel
      of immunostains, including S100, GFAP, MAP2, and NeuN was applied to patients'
      tumor sections as well as the 6 controls from age-matched patients. No
      qualitative histologic or immunohistochemical differences were seen between the
      study cases and control group. Because no qualitative differences were identified
      between the study cases and the control group, testing of paired serum and
      cerebrospinal fluid remains the best method for diagnosis of anti-NMDAR
      encephalitis. Tumor banking with molecular analysis of ovarian teratomas,
      including whole-genome sequencing and comparative genomic hybridization between
      ovarian tissue saved from patients with and without anti-NMDAR encephalitis, is
      necessary to fully understand the etiopathogenesis of anti-NMDAR encephalitis. 

PMID- 25569474
TI  - Modelling the effects of seasonality and socioeconomic impact on the transmission
      of rift valley Fever virus.
AB  - Rift Valley fever (RVF) is an important mosquito-borne viral zoonosis in Africa
      and the Middle East that causes human deaths and significant economic losses due
      to huge incidences of death and abortion among infected livestock. Outbreaks of
      RVF are sporadic and associated with both seasonal and socioeconomic effects.
      Here we propose an almost periodic three-patch model to investigate the
      transmission dynamics of RVF virus (RVFV) among ruminants with spatial movements.
      Our findings indicate that, in Northeastern Africa, human activities, including
      those associated with the Eid al Adha feast, along with a combination of climatic
      factors such as rainfall level and hydrological variations, contribute to the
      transmission and dispersal of the disease pathogen. Moreover, sporadic outbreaks
      may occur when the two events occur together: 1) abundant livestock are recruited
      into areas at risk from RVF due to the demand for the religious festival and 2)
      abundant numbers of mosquitoes emerge. These two factors have been shown to have
      impacts on the severity of RVF outbreaks. Our numerical results present the
      transmission dynamics of the disease pathogen over both short and long periods of
      time, particularly during the festival time. Further, we investigate the impact
      on patterns of disease outbreaks in each patch brought by festival- and seasonal
      driven factors, such as the number of livestock imported daily, the animal
      transportation speed from patch to patch, and the death rate induced by
      ceremonial sacrifices. In addition, our simulations show that when the time for
      festival preparation starts earlier than usual, the risk of massive disease
      outbreaks rises, particularly in patch 3 (the place where the religious ceremony
      will be held). 

PMID- 25569475
TI  - Peptidases compartmentalized to the Ascaris suum intestinal lumen and apical
      intestinal membrane.
AB  - The nematode intestine is a tissue of interest for developing new methods of
      therapy and control of parasitic nematodes. However, biological details of
      intestinal cell functions remain obscure, as do the proteins and molecular
      functions located on the apical intestinal membrane (AIM), and within the
      intestinal lumen (IL) of nematodes. Accordingly, methods were developed to gain a
      comprehensive identification of peptidases that function in the intestinal tract
      of adult female Ascaris suum. Peptidase activity was detected in multiple
      fractions of the A. suum intestine under pH conditions ranging from 5.0 to 8.0.
      Peptidase class inhibitors were used to characterize these activities. The
      fractions included whole lysates, membrane enriched fractions, and physiological-
      and 4 molar urea-perfusates of the intestinal lumen. Concanavalin A (ConA) was
      confirmed to bind to the AIM, and intestinal proteins affinity isolated on ConA
      beads were compared to proteins from membrane and perfusate fractions by mass
      spectrometry. Twenty-nine predicted peptidases were identified including
      aspartic, cysteine, and serine peptidases, and an unexpectedly high number (16)
      of metallopeptidases. Many of these proteins co-localized to multiple fractions,
      providing independent support for localization to specific intestinal
      compartments, including the IL and AIM. This unique perfusion model produced the
      most comprehensive view of likely digestive peptidases that function in these
      intestinal compartments of A. suum, or any nematode. This model offers a means to
      directly determine functions of these proteins in the A. suum intestine and, more
      generally, deduce the wide array functions that exist in these cellular
      compartments of the nematode intestine. 

PMID- 25569476
TI  - Crystal structure, spectroscopic and theoretical studies on two Schiff base
      compounds of 2,6-dichlorobenzylidene-2,4-dichloroaniline and 2,4
      dichlorobenzylidene-2,4-dichloroaniline.
AB  - The crystal structures of two Schiff base compounds, 2,6-dichlorobenzylidene-2,4
      dichloroaniline (1) and 2,4-dichlorobenzylidene-2,4-dichloroaniline (2) have been
      determined from single-crystal X-ray diffraction and characterized by FT-IR and
      (1)H NMR spectroscopy. The electronic structures of compounds 1 and 2 in the gas
      phase were computed by the density functional theory (DFT) method. The obtained
      theoretical results were supported by the crystallographic data. In addition,
      theoretical configurations of the title compounds were relaxed and studied in
      terms of the combined analysis of HOMO-LUMO energy gap, total density of states
      (DOS), molecular electrostatic potential (MEP), NMR spectra and harmonic
      vibrational frequencies. 

PMID- 25569477
TI  - Premium intraocular lens effect on the immediate sequential cataract surgery
      physician perspective cost-analysis model.

PMID- 25569480
TI  - Nutrition and the microbiome 2015.
AB  - Carlo Agostoni, MD, and Kwang Sik Kim, MD, are the Guest Editors for this annual
      review issue on Nutrition and the Microbiome. Dr Agostoni is a Professor of
      Pediatrics at the Department of Clinical Sciences and Community Health,
      University of Milan, within the Fondazione IRCCS Ca Granda Ospedale Maggiore
      Policlinico, Milan. Dr Kim is Professor of Pediatrics and Molecular Microbiology
      and Immunology, Johns Hopkins University School of Medicine and Bloomberg School
      of Public Health; and Director, Division of Pediatric Infectious Diseases, Johns
      Hopkins Children's Center, Baltimore, MD. 

PMID- 25569481
TI  - Long-term effects of 3-month telemetric blood pressure intervention in patients
      with inadequately treated arterial hypertension.
AB  - BACKGROUND AND AIM: We have shown that better blood pressure (BP) control can be
      achieved by using 3-month telemetric BP measurement (TBPM) in comparison with a
      standard-care control group (C-G). The present analysis should clarify if this
      will also lead to a better middle- and long-term BP control. SUBJECTS AND
      METHODS: Fifty-seven patients finished the main study. After the 3 months no TBPM
      was performed. For 40 patients, 18 from the TBPM group (TBPM-G) and 22 from the C
      G, we obtained ambulant BP measurements (ABPMs) with a mean follow-up of 20
      months. Seventeen patients were lost to follow-up. BP target values were defined
      as ABPM <=130/80 or <=125/75 mm Hg with diabetes or renal failure. RESULTS: At
      the end of the follow-up, the systolic BP was 121.2+/-11.2 mm Hg in TBPM-G and
      130.7+/-10.4 mm Hg in C-G, and the diastolic BP was 72.8+/-10.9 versus 77.0+/-7.1
      mm Hg, respectively. Fifty-six percent in TBPM-G versus 40% in C-G (p=0.024) had
      a controlled BP as defined by ABPM criteria. CONCLUSIONS: TBPM helps achieve BP
      target values in patients with previously inadequately treated arterial
      hypertension, and the benefit is sustained. Beyond its immediate application, in
      comparison with standard treatment, TBPM allows for a better BP adjustment in the
      long term as well.

PMID- 25569479
TI  - Phosphorylation of Elp1 by Hrr25 is required for elongator-dependent tRNA
      modification in yeast.
AB  - Elongator is a conserved protein complex comprising six different polypeptides
      that has been ascribed a wide range of functions, but which is now known to be
      required for modification of uridine residues in the wobble position of a subset
      of tRNAs in yeast, plants, worms and mammals. In previous work, we showed that
      Elongator's largest subunit (Elp1; also known as Iki3) was phosphorylated and
      implicated the yeast casein kinase I Hrr25 in Elongator function. Here we report
      identification of nine in vivo phosphorylation sites within Elp1 and show that
      four of these, clustered close to the Elp1 C-terminus and adjacent to a region
      that binds tRNA, are important for Elongator's tRNA modification function. Hrr25
      protein kinase directly modifies Elp1 on two sites (Ser-1198 and Ser-1202) and
      through analyzing non-phosphorylatable (alanine) and acidic, phosphomimic
      substitutions at Ser-1198, Ser-1202 and Ser-1209, we provide evidence that
      phosphorylation plays a positive role in the tRNA modification function of
      Elongator and may regulate the interaction of Elongator both with its accessory
      protein Kti12 and with Hrr25 kinase. 

PMID- 25569484
TI  - Real-time observation of nonclassical protein crystallization kinetics.
AB  - We present a real-time study of protein crystallization of bovine beta
      lactoglobulin in the presence of CdCl(2) using small-angle X-ray scattering and
      optical microscopy. From observing the crystallization kinetics, we propose the
      following multistep crystallization mechanism that is consistent with our data.
      In the first step, an intermediate phase is formed, followed by the nucleation of
      crystals within the intermediate phase. During this period, the number of
      crystals increases with time, but the crystal growth is slowed down by the
      surrounding dense intermediate phase due to the low mobility. In the next step,
      the intermediate phase is consumed by nucleation and slow growth, and the
      crystals are exposed to the dilute phase. In this stage, the number of crystals
      becomes nearly constant, whereas the crystals grow rapidly due to access to the
      free protein molecules in the dilute phase. This real-time study not only
      provides evidence for a two-step nucleation process for protein crystallization
      but also elucidates the role and the structural signature of the metastable
      intermediate phase in this process.

PMID- 25569483
TI  - Investigation of immunomodulatory properties of human Wharton's Jelly-derived
      mesenchymal stem cells after lentiviral transduction.
AB  - Human Wharton's Jelly-derived Mesenchymal Stem Cells (hWJ-MSCs) are considered as
      an alternative for bone-marrow-derived MSCs. These cells have immunosuppressive
      properties. It was unclear whether the WJ-MSCs would sustain their
      immunomodulatory characteristics after lentiviral transduction or not. In this
      study, we evaluated immunomodulatory properties of WJ-MSCs after lentiviral
      transduction. HWJ-MSCs were transduced with lentiviral particles. Expression of
      transduced and un-transduced hWJ-MSCs surface molecules and secretion of IL-10,
      HGF, VEGF and TGF-beta was analyzed. Cell proliferation and frequency of
      CD4(+)CD25(+) CD127(low/neg) Foxp3(+) T regulatory cells was measured. There was
      no difference between the surface markers and secretion of IL-10, HGF, VEGF and
      TGF-beta in transduced and un-transduced hWJ-MSCs. Both cells inhibited the
      proliferation of PHA stimulated PBMCs, and improved the frequency of T regulatory
      cells. These findings suggest that lentiviral transduction does not alter the
      immunomodulatory function of hWJ-MSCs. However, lentiviral transduction may have
      a wide range of applications in gene therapy. 

PMID- 25569482
TI  - Origins of context-dependent gene repression by capicua.
AB  - Receptor Tyrosine Kinase (RTK) signaling pathways induce multiple biological
      responses, often by regulating the expression of downstream genes. The HMG-box
      protein Capicua (Cic) is a transcriptional repressor that is downregulated in
      response to RTK signaling, thereby enabling RTK-dependent induction of Cic
      targets. In both Drosophila and mammals, Cic is expressed as two isoforms, long
      (Cic-L) and short (Cic-S), whose functional significance and mechanism of action
      are not well understood. Here we show that Drosophila Cic relies on the Groucho
      (Gro) corepressor during its function in the early embryo, but not during other
      stages of development. This Gro-dependent mechanism requires a short peptide
      motif, unique to Cic-S and designated N2, which is distinct from other previously
      defined Gro-interacting motifs and functions as an autonomous, transferable
      repressor element. Unexpectedly, our data indicate that the N2 motif is an
      evolutionary innovation that originated within dipteran insects, as the Cic-S
      isoform evolved from an ancestral Cic-L-type form. Accordingly, the Cic-L isoform
      lacking the N2 motif is completely inactive in early Drosophila embryos,
      indicating that the N2 motif endowed Cic-S with a novel Gro-dependent activity
      that is obligatory at this stage. We suggest that Cic-S and Gro coregulatory
      functions have facilitated the evolution of the complex transcriptional network
      regulated by Torso RTK signaling in modern fly embryos. Notably, our results also
      imply that mammalian Cic proteins are unlikely to act via Gro and that their Cic
      S isoform must have evolved independently of fly Cic-S. Thus, Cic proteins employ
      distinct repressor mechanisms that are associated with discrete structural
      changes in the evolutionary history of this protein family. 

PMID- 25569485
TI  - JADA and Elsevier--a new relationship for a new media world.

PMID- 25569486
TI  - Providing clarity on evidence-based prophylactic guidelines for prosthetic joint
      infections.

PMID- 25569487
TI  - Obesity and dental care.

PMID- 25569488
TI  - Nerve injuries.

PMID- 25569489
TI  - Authors' response.

PMID- 25569490
TI  - Author's response.

PMID- 25569491
TI  - Jaw pain.

PMID- 25569493
TI  - The use of prophylactic antibiotics prior to dental procedures in patients with
      prosthetic joints: Evidence-based clinical practice guideline for dental
      practitioners--a report of the American Dental Association Council on Scientific
      Affairs.
AB  - BACKGROUND: A panel of experts (the 2014 Panel) convened by the American Dental
      Association Council on Scientific Affairs developed an evidence-based clinical
      practice guideline (CPG) on the use of prophylactic antibiotics in patients with
      prosthetic joints who are undergoing dental procedures. This CPG is intended to
      clarify the "Prevention of Orthopaedic Implant Infection in Patients Undergoing
      Dental Procedures: Evidence-based Guideline and Evidence Report," which was
      developed and published by the American Academy of Orthopaedic Surgeons and the
      American Dental Association (the 2012 Panel). TYPES OF STUDIES REVIEWED: The 2014
      Panel based the current CPG on literature search results and direct evidence
      contained in the comprehensive systematic review published by the 2012 Panel, as
      well as the results from an updated literature search. The 2014 Panel identified
      4 case-control studies. RESULTS: The 2014 Panel judged that the current best
      evidence failed to demonstrate an association between dental procedures and
      prosthetic joint infection (PJI). The 2014 Panel also presented information about
      antibiotic resistance, adverse drug reactions, and costs associated with
      prescribing antibiotics for PJI prophylaxis. PRACTICAL IMPLICATIONS AND
      CONCLUSIONS: The 2014 Panel made the following clinical recommendation: In
      general, for patients with prosthetic joint implants, prophylactic antibiotics
      are not recommended prior to dental procedures to prevent prosthetic joint
      infection. The practitioner and patient should consider possible clinical
      circumstances that may suggest the presence of a significant medical risk in
      providing dental care without antibiotic prophylaxis, as well as the known risks
      of frequent or widespread antibiotic use. As part of the evidence-based approach
      to care, this clinical recommendation should be integrated with the
      practitioner's professional judgment and the patient's needs and preferences.

PMID- 25569494
TI  - Oral health knowledge among elderly patients.
AB  - BACKGROUND: The purpose of this study was to determine the level of oral health
      knowledge among patients 65 years or older to identify areas in which knowledge
      gaps exist. METHODS: The authors administered the Comprehensive Measure of Oral
      Health Knowledge questionnaire to patients 65 years or older at a university
      based dental clinic and examined associations between oral health knowledge
      scores and participants' demographic and dental characteristics. RESULTS: Most
      participants were familiar with basic dental disease prevention and treatment;
      however, many participants were unfamiliar with concepts pertaining to
      periodontal disease, oral cancer, and children's oral health. CONCLUSIONS:
      Advocates for geriatric oral health should educate elderly populations about the
      risk factors associated with periodontal disease and oral cancer, especially as
      they become more at risk of experiencing these diseases. PRACTICAL IMPLICATIONS:
      Educational messages aimed at both routine and nonroutine users of dental care
      should be developed on the basis of universal health literacy principles to
      facilitate understanding among elderly adults, who have varying literacy levels.

PMID- 25569495
TI  - Comparison of suction device with saliva ejector for aerosol and spatter
      reduction during ultrasonic scaling.
AB  - BACKGROUND: Aerosols and spatter are concerns in health care owing to their
      potential adverse health effects. The Isolite illuminated isolation system
      (Isolite Systems) and a saliva ejector were compared for aerosol and spatter
      reduction during and after ultrasonic scaling. METHODS: Fifty participants were
      randomized to control (n = 25, saliva ejector) or test (n = 25, Isolite) groups
      and received a prophylaxis with an ultrasonic scaler. Aerosols were collected in
      a petri dish containing transport media, dispersed, and plated to anaerobic blood
      agar to determine colony-forming units (CFUs). The authors analyzed the data
      using a t test. RESULTS: No significant difference occurred between groups in
      aerosol and spatter reduction (P = .25). Mean (standard deviation) of log10 CFUs
      per milliliter collected during ultrasonic scaling in the control and test groups
      were 3.61 (0.95) and 3.30 (0.88), respectively. All samples contained alpha
      hemolytic streptococci, and many samples contained strictly oral anaerobes.
      CONCLUSIONS: A significant amount of contamination occurred during ultrasonic
      scaling in both groups, as indicated by high numbers of CFUs and the
      identification of strictly oral anaerobes in all plates. PRACTICAL IMPLICATIONS:
      Neither device reduced aerosols and spatter effectively, and there was no
      significant difference in reduction between the 2 devices. Additional measures
      should be taken with these devices to reduce the likelihood of disease
      transmission.

PMID- 25569496
TI  - The relationship between altruistic attitudes and dentists' Medicaid
      participation.
AB  - BACKGROUND: The authors investigated the role of private practitioners in the
      dental safety net, including the provision of care for Medicaid enrollees and
      attitudinal factors that affect participation. METHODS: In 2013, the authors sent
      a mixed-mode survey to all general dentists in Iowa assessing their current
      Medicaid participation and factors affecting participation, including attitudinal
      statements about altruism, the Medicaid program, and the government's role in
      providing access to dental care. RESULTS: Fifty-six percent of responding
      dentists accepted new Medicaid-enrolled patients; dentists living in
      nonmetropolitan areas were significantly more likely to accept Medicaid than were
      those in metropolitan areas. Results from a logistic regression model
      demonstrated that participating dentists scored significantly higher in
      altruistic attitudes and perceived problems with Medicaid as less important.
      CONCLUSIONS: Dentists who accepted Medicaid-enrolled patients had significantly
      more positive attitudes about Medicaid administration and altruistic attitudes in
      general. Investigators in future studies should examine how these attitudes are
      shaped by educational and professional experiences. PRACTICAL IMPLICATIONS:
      Dentists' perceptions about Medicaid potentially are modifiable by changing
      program policies in ways to improve access for vulnerable populations, including
      new Medicaid enrollees.

PMID- 25569497
TI  - A practical approach to evidence-based dentistry: III: how to appraise and use an
      article about therapy.
AB  - BACKGROUND AND OVERVIEW: Dental practitioners spend most of their time
      administering treatments. To ensure that their clinical decisions are informed by
      the best available evidence, dental practitioners need to be skilled in
      critically appraising studies addressing therapy issues. Randomized controlled
      trials offer the optimal study design to inform decisions regarding therapy. The
      critical appraisal of randomized controlled trials involves assessing the risk of
      bias, results, and applicability. In this article, the authors present these
      concepts and provide guidance for this type of appraisal. PRACTICAL IMPLICATIONS:
      Dentists who wish to inform their clinical decisions regarding therapy and
      prevention questions can use these guidelines to decide what type of studies to
      search, define the specific question of interest to search efficiently for these
      studies, and critically appraise an article about therapy or prevention.

PMID- 25569498
TI  - Protecting your practice.
AB  - BACKGROUND AND OVERVIEW: Dentists have much invested in their practices. They
      need to protect their practices from fraud and noncompliance. The author provides
      practical suggestions for how to significantly reduce the risk of fraud and theft
      in the practice without disrupting day-to-day operations. CONCLUSIONS: By
      adhering to nonintrusive policy and procedure changes, dental practice owners can
      reduce inherent risks of fraud and theft, while increasing financial and human
      resource knowledge regarding their practice. PRACTICAL IMPLICATIONS: Practice
      owners with the appropriate policies and procedures benefit from significantly
      lower risk of loss from fraud and theft. Furthermore, they have a better
      understanding of their practice's finances and human resources.

PMID- 25569499
TI  - Impact of fee increases on dental utilization rates for children living in
      Connecticut and enrolled in Medicaid.
AB  - BACKGROUND: In 2008, Connecticut's Medicaid program administration increased
      children's dental fees to match approximately the 70th percentile of what the
      market fees were for dental care in 2005. These Medicaid program changes occurred
      at the same time as a national economic recession, which took place from 2007
      through 2009. METHODS: The authors obtained Medicaid eligibility, claims, and
      provider data before and after the fee increase, in 2006 and 2009 through 2012,
      respectively. Their analysis examined changes in utilization rates, service mix,
      expenditures, and dentists' participation. The authors qualitatively assessed the
      general impact of the recession on utilization rate changes. RESULTS: The
      Medicaid fee increase, program improvements, and the recession resulted in a
      dramatic increase in utilization rates. For children continuously enrolled in
      Medicaid, utilization rates increased from 45.9% in 2006 to 71.6% in 2012. Rates
      increased across sex, race, ethnicity, and geographic areas. These increased
      utilization rates eliminated the disparities in access to dental services between
      children with private insurance and children receiving Medicaid benefits.
      Children enrolled in Medicaid now have utilization rates that are similar to or
      higher than privately insured children. Expenditures increased $62 million; this
      represents less than 1% of 2012 State Medicaid expenditures. Dentist
      participation increased by 72%. These results suggest that dentists will
      participate in the Medicaid program if adequately compensated, and low-income
      families will seek dental services. CONCLUSION: The Medicaid fee increase,
      program improvements, and the recession had a dramatic impact on reducing
      disparities in children's access to dental care in Connecticut. PRACTICAL
      IMPLICATIONS: One solution to the substantial disparities in access to dental
      care is to increase Medicaid fees to competitive levels.

PMID- 25569500
TI  - Nomenclature, characteristics, and dietary intakes of sugars.
AB  - BACKGROUND AND OVERVIEW: The World Health Organization has recommended a
      reduction in free sugars intake throughout one's life span to decrease the burden
      of noncommunicable diseases, including caries and obesity. The author defines
      sugars' nomenclature, describes sugars' roles in food, and identifies current
      sugars intake. CONCLUSIONS: The oral health care practitioner can identify added
      sugars intake and provide guidance to patients to decrease their intake of added
      sugars while improving nutrient intake and reducing caries risk. PRACTICAL
      IMPLICATIONS: Intake of added sugars increases the burden of chronic diseases in
      the United States. The oral health care practitioner is in a position to provide
      dietary guidance to patients to reduce both oral and systemic diseases.

PMID- 25569502
TI  - Peri-implant marginal bone loss is minimal after 5 years of function.

PMID- 25569503
TI  - Dealing with good intentions that go bad.

PMID- 25569505
TI  - Epidemiology of cholera in the Philippines.
AB  - BACKGROUND: Despite being a cholera-endemic country, data on cholera in the
      Philippines remain sparse. Knowing the areas where cholera is known to occur and
      the factors that lead to its occurrence will assist in planning preventive
      measures and disaster mitigation. METHODS: Using sentinel surveillance data,
      PubMed and ProMED searches covering information from 2008-2013 and event-based
      surveillance reports from 2010-2013, we assessed the epidemiology of cholera in
      the Philippines. Using spatial log regression, we assessed the role of water,
      sanitation and population density on the incidence of cholera. RESULTS AND
      DISCUSSION: We identified 12 articles from ProMED and none from PubMed that
      reported on cholera in the Philippines from 2008 to 2013. Data from ProMed and
      surveillance revealed 42,071 suspected and confirmed cholera cases reported from
      2008 to 2013, among which only 5,006 were confirmed. 38 (47%) of 81 provinces and
      metropolitan regions reported at least one confirmed case of cholera and 32 (40%)
      reported at least one suspected case. The overall case fatality ratio in sentinel
      sites was 0.62%, but was 2% in outbreaks. All age groups were affected. Using
      both confirmed and suspected cholera cases, the average annual incidence in 2010
      2013 was 9.1 per 100,000 population. Poor access to improved sanitation was
      consistently associated with higher cholera incidence. Paradoxically, access to
      improved water sources was associated with higher cholera incidence using both
      suspected and confirmed cholera data sources. This finding may have been due to
      the breakdown in the infrastructure and non-chlorination of water supplies,
      emphasizing the need to maintain public water systems. CONCLUSION: Our findings
      confirm that cholera affects a large proportion of the provinces in the country.
      Identifying areas most at risk for cholera will support the development and
      implementation of policies to minimize the morbidity and mortality due to this
      disease.

PMID- 25569506
TI  - Effect of traditional and resisted sprint training in highly trained female team
      handball players.
AB  - Fast acceleration is an important performance factor in handball. In addition to
      traditional sprint training (TST), resisted-sprint training (RST) is a method
      often used to improve acceleration. However, studies on RST show conflicting
      results, and underlying mechanisms have not been studied. PURPOSE: To compare the
      effects of RST, by sled towing, against TST on sprint performance and muscle
      architecture. METHODS: Participants (n=18) were assigned to either RST or TST and
      completed 2 training sessions of RST or TST per week (10 wk), in addition to
      their normal team training. Sprint tests (10 and 30 m) and measurements of muscle
      architecture were performed pre- and posttraining. RESULTS: Beneficial effects
      were found in the 30-m-sprint test for both groups (mean; +/-90% CL: TST=-0.31;
      +/-0.19 s, RST=-0.16; +/-0.13 s), with unclear differences between the groups.
      Only TST had a beneficial effect on 10-m time (-0.04; +/-0.04 s), with a likely
      difference between the 2 groups (85%, ES=0.60). Both groups had a decrease in
      pennation angle (-6.0; +/-3.3% for TST and -2.8; +/-2.0% for RST), which had a
      nearly perfect correlation with percentage change in 10-m-sprint performance
      (r=.92). A small increase in fascicle length (5.3; +/-3.9% and 4.0; +/-2.1% for
      TST and RST, respectively) was found, with unclear differences between groups.
      DISCUSSION: TST appears to be more effective than RST in enhancing 10-m-sprint
      time. Both groups showed similar effects in 30-m-sprint time. A similar, yet
      small, effect of sprint training on muscle architecture was observed in both
      groups.

PMID- 25569504
TI  - Novel inhibitors induce large conformational changes of GAB1 pleckstrin homology
      domain and kill breast cancer cells.
AB  - The Grb2-associated binding protein 1 (GAB1) integrates signals from different
      signaling pathways and is over-expressed in many cancers, therefore representing
      a new therapeutic target. In the present study, we aim to target the pleckstrin
      homology (PH) domain of GAB1 for cancer treatment. Using homology models we
      derived, high-throughput virtual screening of five million compounds resulted in
      five hits which exhibited strong binding affinities to GAB1 PH domain. Our
      prediction of ligand binding affinities is also in agreement with the
      experimental KD values. Furthermore, molecular dynamics studies showed that GAB1
      PH domain underwent large conformational changes upon ligand binding. Moreover,
      these hits inhibited the phosphorylation of GAB1 and demonstrated potent, tumor
      specific cytotoxicity against MDA-MB-231 and T47D breast cancer cell lines. This
      effort represents the discovery of first-in-class GAB1 PH domain inhibitors with
      potential for targeted breast cancer therapy and provides novel insights into
      structure-based approaches to targeting this protein. 

PMID- 25569507
TI  - Kinematic study of ozurdex injection in balanced salt solution: modeling the
      behavior of an injectable drug delivery device in vitrectomized eyes.
AB  - PURPOSE: To analyze the kinematics of a dexamethasone intravitreal implant,
      Ozurdex, after its injection in a balanced salt solution (BSS) at different
      release angles to simulate its movement in BSS/aqueous-filled eyes. METHODS:
      Eighteen Ozurdex implants were injected into a BSS-filled box at different
      release angles (15 degrees , 30 degrees , 45 degrees ), using 6 implants/group.
      The movement of injected implants was recorded by a high-speed video camera. Each
      implant's trajectory was graphically demonstrated by plotting over time. By using
      a distance-time function graph, the implant's velocity and normalized energy were
      calculated. RESULTS: The high-speed video revealed that implants injected at 15
      degrees  followed a more horizontal trajectory compared to those injected from 30
      degrees  and 45 degrees , respectively. The implant injected at 15 degrees  also
      achieved the highest mean initial velocity and mean initial normalized energy.
      The implant velocity from each injection angle decreased exponentially over time
      and reached nearly zero at 0.1 s. An injection of the implant at a flatter angle
      was also associated with higher mean retinal impact normalized energy.
      CONCLUSIONS: An implant injected at a flatter angle tends to travel farther in
      the horizontal plane and has more initial velocity, which theoretically generates
      higher initial normalized energy and retinal impact normalized energy. The
      accidental injection at a flatter angle, which results in shortening of the
      effective travel distance, may carry the potential risk of direct retinal injury
      from the injected implant. The amount of energy necessary to cause direct retinal
      injury, and whether this would be clinically significant, requires further study.

PMID- 25569508
TI  - Are LGBT populations at a higher risk for suicidal behaviors in Australia?
      Research findings and implications.
AB  - The aim of this article is to review the Australian literature about suicidality
      in minority sexual identity and/or behavior groups in order to determine the
      evidence base for their reported higher vulnerability to suicidal behaviors than
      heterosexual and non-transgendered individuals in the Australian context, as well
      as to identify the factors that are predictive of suicidal behaviors in these
      groups in Australia. A literature search for all available years (until the end
      of 2012) was conducted using the databases Scopus, Medline, and Proquest for
      articles published in English in peer-reviewed academic journals. All peer
      reviewed publications that provided empirical evidence for prevalence and
      predictive factors of suicidal behaviors among LGBT individuals (or a subset
      thereof) in Australia were included. Reference lists were also scrutinized to
      identify "gray" literature for inclusion. The results revealed that there is only
      limited research from Australia. Nevertheless, although no population-based
      studies have been published, research indicates that sexual minorities are indeed
      at a higher risk for suicidal behaviors. In order to further the understanding of
      suicidal behaviors and potential prevention among LGBT groups in the Australia,
      further research is needed, particularly on fatal suicidal behaviors. 

PMID- 25569511
TI  - Correlating hydrogen oxidation and evolution activity on platinum at different pH
      with measured hydrogen binding energy.
AB  - The hydrogen oxidation/evolution reactions are two of the most fundamental
      reactions in distributed renewable electrochemical energy conversion and storage
      systems. The identification of the reaction descriptor is therefore of critical
      importance for the rational catalyst design and development. Here we report the
      correlation between hydrogen oxidation/evolution activity and experimentally
      measured hydrogen binding energy for polycrystalline platinum examined in several
      buffer solutions in a wide range of electrolyte pH from 0 to 13. The hydrogen
      oxidation/evolution activity obtained using the rotating disk electrode method is
      found to decrease with the pH, while the hydrogen binding energy, obtained from
      cyclic voltammograms, linearly increases with the pH. Correlating the hydrogen
      oxidation/evolution activity to the hydrogen binding energy renders a monotonic
      decreasing hydrogen oxidation/evolution activity with the hydrogen binding
      energy, strongly supporting the hypothesis that hydrogen binding energy is the
      sole reaction descriptor for the hydrogen oxidation/evolution activity on
      monometallic platinum. 

PMID- 25569510
TI  - Genetic Deletion of beta-Arrestin-2 and the Mitigation of Established Airway
      Hyperresponsiveness in a Murine Asthma Model.
AB  - beta-Arrestin-2 (betaarr2) is a ubiquitously expressed cytosolic protein that
      terminates G protein-coupled receptor signaling and transduces G protein
      independent signaling. We previously showed that mice lacking betaarr2 do not
      develop an asthma phenotype when sensitized to, and challenged with, allergens.
      The current study evaluates if an established asthma phenotype can be mitigated
      by deletion of betaarr2 using an inducible Cre recombinase. We sensitized and
      challenged mice to ovalbumin (OVA) and demonstrated that on Day (d) 24 the
      allergic asthma phenotype was apparent in uninduced betaarr2 and wild-type (WT)
      mice. In a second group of OVA-treated mice, tamoxifen was injected on d24 to d28
      to activate Cre recombinase, and OVA aerosol challenge was continued through d44.
      The asthma phenotype was assessed using lung mechanics measurements,
      bronchoalveolar lavage cell analysis, and histological assessment of mucin and
      airway inflammation. Compared with their respective saline-treated controls, OVA
      treated WT mice and mice expressing the inducible Cre recombinase displayed a
      significant asthma phenotype at d45. Whereas tamoxifen treatment had no
      significant effect on the asthma phenotype in WT mice, it inhibited betaarr2
      expression and caused a significant reduction in airway hyper-responsiveness
      (AHR) in Cre-inducible mice. These findings suggest that betaarr2 is actively
      required for perpetuation of the AHR component of the allergic asthma phenotype.
      Our finding that betaarr2 participates in the perpetuation of AHR in an asthma
      model means that targeting betaarr2 may provide immediate and potentially long
      term relief from daily asthma symptoms due to AHR irrespective of inflammation. 

PMID- 25569512
TI  - Insights into animal and plant lectins with antimicrobial activities.
AB  - Lectins are multivalent proteins with the ability to recognize and bind diverse
      carbohydrate structures. The glyco -binding and diverse molecular structures
      observed in these protein classes make them a large and heterogeneous group with
      a wide range of biological activities in microorganisms, animals and plants.
      Lectins from plants and animals are commonly used in direct defense against
      pathogens and in immune regulation. This review focuses on sources of animal and
      plant lectins, describing their functional classification and tridimensional
      structures, relating these properties with biotechnological purposes, including
      antimicrobial activities. In summary, this work focuses on structural-functional
      elucidation of diverse lectin groups, shedding some light on host-pathogen
      interactions; it also examines their emergence as biotechnological tools through
      gene manipulation and development of new drugs. 

PMID- 25569513
TI  - Phenolic composition from different loquat (Eriobotrya japonica Lindl.) cultivars
      grown in China and their antioxidant properties.
AB  - China is one of the most important centers of diversity for Eriobotrya japonica
      Lindl. in the world. In this study, seven loquat cultivars grown in China were
      evaluated for their phenolic compounds and antioxidant activity. Eleven phenolic
      compounds, i.e., 3-p-coumaroylquinincacid (3-p-CoQA), 5-caffeoylquinic acid (5
      CQA), 4-caffeoylquinic acid (4-CQA), 3-caffeoylquinic acid (3-CQA), 5
      feruloylquinic acid (5-FQA), quercetin-3-O-galactoside (Q-3-Gal), quercetin-3-O
      glucoside (Q-3-Glu), quercetin-3-O-rhamnoside (Q-3-Rha), kaempferol-3-O
      galactoside (K-3-Gal), kaempferol-3-O-rhamnoside (K-3-Rha), and kaempferol-3-O
      glucoside (K-3-Glu) were identified and quantified in the peel and pulp of the
      cultivars tested. 3-CQA and 5-CQA were the predominant components in both fruit
      parts. 2,2-Diphenyl-1-picrylhydrazyl radicals (DPPH), 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonate (ABTS), and ferric reducing antioxidant power
      (FRAP) assays were used for the antioxidant evaluation. Results showed that peel
      extracts had higher antioxidant activities than their pulp counterparts in all
      the cultivars tested, which was correlated with their higher total phenolic
      contents. The antioxidant potency composite (APC) index showed obvious variations
      ranging from 64.15 to 100 in the peel and from 59.49 to 97.95 in the pulp of
      different cultivars, where "Dahongpao" (DHP) and "Luoyangqing" (LYQ) had the
      highest APC index in the peel and pulp, respectively. Overall, loquat cultivars
      rich in hydroxycinnamic acids (HCAs) such as 3-p-CoQA, 5-CQA, 4-CQA, 3-CQA and 5
      FQA showed relatively higher antioxidant activities, and may be excellent sources
      of phytochemicals and natural antioxidants. 

PMID- 25569514
TI  - Decreasing pH results in a reduction of anthocyanin coprecipitation during cold
      stabilization of purple grape juice.
AB  - Anthocyanin pigments in grape juice can coprecipitate with potassium bitartrate
      (KHT) crystals during cold stabilization, but factors that reduce these
      adsorptive losses are not well understood. We hypothesized that coprecipitation
      on a % w/w basis should be decreased at lower pH. In initial experiments, model
      juice solutions containing an anthocyanin monoglucoside extract and varying pH
      values were subjected to cold-storage to induce KHT crystallization, and
      anthocyanins in the resulting precipitant were characterized by HPLC. The pH of
      the model juice was directly correlated with the % w/w concentration of
      anthocyanins in the KHT crystals, with a maximum observed at pH 3.40 (0.20% w/w)
      and a minimum at pH 2.35 (0.01% w/w). A pH dependency was also observed for
      anthocyanin-KHT coprecipitation in purple Concord grape juice, although the
      effect was smaller. Coprecipitation was significantly greater for anthocyanin
      monoglucosides and acylated anthocyanins as compared to anthocyanin diglucosides
      at pH > 3.05, but coprecipitation of mono- and acylated forms declined more
      sharply at lower pH values. 

PMID- 25569515
TI  - Halofuginone - the multifaceted molecule.
AB  - Halofuginone is an analog of febrifugine-an alkaloid originally isolated from the
      plant Dichroa febrifuga. During recent years, halofuginone has attracted much
      attention because of its wide range of beneficial biological activities, which
      encompass malaria, cancer, and fibrosis-related and autoimmune diseases. At
      present two modes of halofuginone actions have been described: (1) Inhibition of
      Smad3 phosphorylation downstream of the TGFbeta signaling pathway results in
      inhibition of fibroblasts-to-myofibroblasts transition and fibrosis. (2)
      Inhibition of prolyl-tRNA synthetase (ProRS) activity in the blood stage of
      malaria and inhibition of Th17 cell differentiation thereby inhibiting
      inflammation and the autoimmune reaction by activation of the amino acid
      starvation and integrated stress responses. This review deals with the history
      and origin of this natural product, its synthesis, its known modes of action, and
      it's various biological activities in pre-clinical animal models and in humans. 

PMID- 25569516
TI  - Preparation, cell compatibility and degradability of collagen-modified
      poly(lactic acid).
AB  - Poly(lactic acid) (PLA) was modified using collagen through a grafting method to
      improve its biocompatibility and degradability. The carboxylic group at the open
      end of PLA was transferred into the reactive acylchlorided group by a reaction
      with phosphorus pentachloride. Then, collagen-modified PLA (collagen-PLA) was
      prepared by the reaction between the reactive acylchlorided group and
      amino/hydroxyl groups on collagen. Subsequently, the structure of collagen-PLA
      was confirmed by Fourier transform infrared spectroscopy, fluorescein
      isothiocyanate-labeled fluorescence spectroscopy, X-ray photoelectron
      spectroscopy, and DSC analyses. Finally, some properties of collagen-PLA, such as
      hydrophilicity, cell compatibility and degradability were characterized. Results
      showed that collagen had been grafted onto the PLA with 5% graft ratio. Water
      contact angle and water absorption behavior tests indicated that the
      hydrophilicity of collagen-PLA was significantly higher than that of PLA. The
      cell compatibility of collagen-PLA with mouse embryonic fibroblasts (3T3) was
      also significantly better than PLA in terms of cell morphology and cell
      proliferation, and the degradability of PLA was also improved after introducing
      collagen. Results suggested that collagen-PLA was a promising candidate for
      biomedical applications. 

PMID- 25569517
TI  - Plasmin regulation through allosteric, sulfated, small molecules.
AB  - Plasmin, a key serine protease, plays a major role in clot lysis and
      extracellular matrix remodeling. Heparin, a natural polydisperse sulfated
      glycosaminoglycan, is known to allosterically modulate plasmin activity. No small
      allosteric inhibitor of plasmin has been discovered to date. We screened an in
      house library of 55 sulfated, small glycosaminoglycan mimetics based on nine
      distinct scaffolds and varying number and positions of sulfate groups to discover
      several promising hits. Of these, a pentasulfated flavonoid-quinazolinone dimer
      32 was found to be the most potent sulfated small inhibitor of plasmin (IC50 = 45
      MUM, efficacy = 100%). Michaelis-Menten kinetic studies revealed an allosteric
      inhibition of plasmin by these inhibitors. Studies also indicated that the most
      potent inhibitors are selective for plasmin over thrombin and factor Xa, two
      serine proteases in coagulation cascade. Interestingly, different inhibitors
      exhibited different levels of efficacy (40%-100%), an observation alluding to the
      unique advantage offered by an allosteric process. Overall, our work presents the
      first small, synthetic allosteric plasmin inhibitors for further rational design.

PMID- 25569519
TI  - Molecules after 20 years-looking back and looking forward.

PMID- 25569518
TI  - Optimization of astilbin extraction from the rhizome of Smilax glabra, and
      evaluation of its anti-inflammatory effect and probable underlying mechanism in
      lipopolysaccharide-induced RAW264.7 macrophages.
AB  - Astilbin, a dihydroflavonol derivative found in many food and medicine plants,
      exhibited multiple pharmacological functions. In the present study, the ethanol
      extraction of astilbin from the rhizome of smilax glabra Roxb was optimized by
      response surface methodology (RSM) using Box-Behnken design. Results indicated
      that the obtained experimental data was well fitted to a second-order polynomial
      equation by using multiple regression analysis, and the optimal extraction
      conditions were identified as an extraction time of 40 min, ethanol concentration
      of 60%, temperature of 73.63  degrees C, and liquid-solid ratio of 29.89 mL/g for
      the highest predicted yield of astilbin (15.05 mg/g), which was confirmed through
      validation experiments. In addition, the anti-inflammatory efficiency of astilbin
      was evaluated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed
      that astilbin, at non-cytotoxicity concentrations, significantly suppressed the
      production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), as
      well as the mRNA expression of inducible nitric oxide synthase (iNOS) and TNF
      alpha in LPS-induced RAW 264.7 cells, but did not affect interleukin-6 (IL-6)
      release or its mRNA expression. These effects may be related to its up-regulation
      of the phosphorylation of p65, extracellular signal-regulated kinases 1/2
      (ERK1/2) and c-Jun N-terminal kinase (JNK). 

PMID- 25569520
TI  - Lectins with anti-HIV activity: a review.
AB  - Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins,
      actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins
      and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include
      Artocarpus heterophyllus (jacalin) lectin, concanavalin A, Galanthus nivalis
      (snowdrop) agglutinin-related lectins, Musa acuminata (banana) lectin, Myrianthus
      holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin.
      The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin,
      Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are
      cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin
      is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include
      Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea
      worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus). The anti
      HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti
      HIV mechanisms are discussed. 

PMID- 25569521
TI  - A synergistic, balanced antioxidant cocktail, protects aging rats from insulin
      resistance and absence of meal-induced insulin sensitization (AMIS) syndrome.
AB  - A series of in vivo and in vitro studies using animal and human models in the
      past 15 years have demonstrated that approximately 55% (~66% in humans) of the
      glucose disposal effect of an i.v. injection of insulin in the fed state is
      dependent on the action of a second hormone, hepatic insulin sensitizing
      substance (HISS), which is released from the liver and stimulates glucose uptake
      in muscle, heart and kidneys. Sensitization of the insulin response by a meal
      through release of HISS is called meal-induced insulin sensitization (MIS).
      Absence of HISS action results in postprandial hyperglycemia, hyperinsulinemia,
      hyperlipidemia, adiposity, increased free radical stress and a cluster of
      progressive metabolic and cardiovascular dysfunctions referred to as the AMIS
      (absence of meal-induced insulin sensitization) syndrome. Reduced HISS release
      accounts for the insulin resistance that occurs with aging and is made worse by
      physical inactivity and diets high in sucrose or fat. This brief review provides
      an update of major metabolic disturbances associated with aging due to reduction
      of HISS release, and the protection against these pathological changes in aging
      animals using a balanced synergistic antioxidant cocktail SAMEC (S
      adenosylmethionine, vitamins E and C). The synergy amongst the components is
      consistent with the known benefits of antioxidants supplied by a mixed diet and
      acting through diverse mechanisms. Using only three constituents, SAMEC appears
      suitable as an antioxidant specifically targeting the AMIS syndrome. 

PMID- 25569523
TI  - Enhanced phenylpyruvic acid production with Proteus vulgaris in fed-batch and
      continuous fermentation.
AB  - Phenylpyruvic acid is a deaminated form of phenylalanine and is used in various
      areas such as development of cheese and wine flavors, diagnosis of
      phenylketonuria, and to decrease excessive nitrogen accumulation in the manure of
      farm animals. However, reported phenylpyruvic acid fermentation studies in the
      literature have been usually performed at shake-flask scale with low production.
      In this study, phenylpyruvic acid production was evaluated in bench-top
      bioreactors by conducting fed-batch and continuous fermentation for the first
      time. As a result, maximum phenylpyruvic acid concentrations increased from 1350
      mg/L (batch fermentation) to 2958 mg/L utilizing fed-batch fermentation.
      Furthermore, phenylpyruvic acid productivity was increased from 48 mg/L/hr (batch
      fermentation) to 104 and 259 mg/L/hr by conducting fed-batch and continuous
      fermentation, respectively. Overall, this study demonstrated that fed-batch and
      continuous fermentation significantly improved phenylpyruvic acid production in
      bench-scale bioreactor production.

PMID- 25569522
TI  - Salvianolic acid Y: a new protector of PC12 cells against hydrogen peroxide
      induced injury from Salvia officinalis.
AB  - Salvianolic acid Y (TSL 1), a new phenolic acid with the same planar structure as
      salvianolic acid B, was isolated from Salvia officinalis. The structural
      elucidation and stereochemistry determination were achieved by spectroscopic and
      chemical methods, including 1D, 2D-NMR (1H-1H COSY, HMQC and HMBC) and circular
      dichroism (CD) experiments. The biosynthesis pathway of salvianolic acid B and
      salvianolic acid Y (TSL 1) was proposed based on structural analysis. The
      protection of PC12 cells from injury induced by H2O2 was assessed in vitro using
      a cell viability assay. Salvianolic acid Y (TSL 1) protected cells from injury by
      54.2%, which was significantly higher than salvianolic acid B (35.2%). 

PMID- 25569525
TI  - Point of view.

PMID- 25569524
TI  - Long-term outcomes of lumbar spinal stenosis: eight-year results of the Spine
      Patient Outcomes Research Trial (SPORT).
AB  - STUDY DESIGN: Randomized trial with a concurrent observational cohort study.
      OBJECTIVE: To compare 8-year outcomes of surgery with nonoperative care for
      symptomatic lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: Surgery for
      spinal stenosis has been shown to be more effective than nonoperative treatment
      during 4 years, but longer-term data are less clear. METHODS: Surgical candidates
      from 13 centers in 11 US states with at least 12 weeks of symptoms and
      confirmatory imaging were enrolled in a randomized cohort or observational
      cohort. Treatment was standard, decompressive laminectomy versus standard
      nonoperative care. Primary outcomes were SF-36 (MOS 36-Item Short-Form Health
      Survey) Bodily Pain and Physical Function scales and the modified Oswestry
      Disability Index assessed at 6 weeks, 3 months, 6 months, and yearly up to 8
      years. RESULTS: Data were obtained for 55% of participants in the randomized
      group and 52% of participants in the observational group at the 8-year follow-up.
      Intent-to-treat analyses showed no differences between randomized cohorts;
      however, 70% of those randomized to surgery and 52% of those randomized to
      nonoperative had undergone surgery by 8 years. As-treated analyses in the
      randomized group showed that the early benefit for surgery out to 4 years
      converged over time, with no significant treatment effect of surgery seen in
      years 6 to 8 for any of the primary outcomes. In contrast, the observational
      group showed a stable advantage for surgery in all outcomes between years 5 and
      8. Patients who were lost to follow-up were older, less well-educated, sicker,
      and had worse outcomes during the first 2 years in both surgical and nonoperative
      arms. CONCLUSION: Patients with symptomatic spinal stenosis show diminishing
      benefits of surgery in as-treated analyses of the randomized group between 4 and
      8 years, whereas outcomes in the observational group remained stable. Loss to
      follow-up of patients with worse early outcomes in both treatment groups could
      lead to overestimates of long-term outcomes but likely not bias treatment effect
      estimates.

PMID- 25569526
TI  - Enhanced expression of neurotrophic factors in the injured spinal cord through
      vaccination with myelin basic protein-derived peptide pulsed dendritic cells.
AB  - STUDY DESIGN: Vaccination of spinal cord injury (SCI) mice with myelin basic
      protein-derived peptide (A91) pulsed dendritic cells (DC) to enhance brain
      derived neurotrophic factor and neurotrophin-3 (NT-3) expression in injured
      spinal cord. OBJECTIVE: To investigate the effect of A91-pulsed DC (A91-DC) on
      expression of neurotrophic factor in injured spinal cord. SUMMARY OF BACKGROUND
      DATA: SCI leads to progressive secondary tissue degeneration, and no satisfactory
      treatment is currently available. Accumulating evidence indicates that
      administration of neurotrophic factors to injured spinal cord is partially
      successful at promoting nerve tissue repair. However, most of strategy can cause
      secondary injury and limiting their wide clinical application. METHODS:
      Proliferation of T cells and the capability of CD4 T cells to secret neurotrophic
      factors were first measured in vitro to demonstrate the stimulus action of the
      A91-DC. In SCI mice model, enzyme-linked immunosorbent assay and
      immunofluorescence was employed to investigate the brain-derived neurotrophic
      factor and NT-3 expression in injured spinal cord. Furthermore, the
      neuroprotective effect of A91-DC in injured spinal cord was examined through
      histology measurement. RESULTS: In this study, we demonstrated that A91-DC
      promoted the capability of T cells to secret neurotrophic factors and in the
      subacute phase of SCI. Moreover, vaccination with A91-DC enhanced the expression
      level of brain-derived neurotrophic factor and NT-3 and exerted neuroprotective
      effect in injured spinal cord. CONCLUSION: The findings of study demonstrate that
      the therapeutic strategy of vaccination A91-DC is a potential minimally invasive
      approach that could provide strong neurotrophic factor support after SCI.

PMID- 25569527
TI  - Pre- and postoperative spinopelvic sagittal balance in adolescent patients with
      lenke type 5 idiopathic scoliosis.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the preoperative
      spinopelvic sagittal alignment in Lenke 5 patients with adolescent idiopathic
      scoliosis (AIS), and analyze how it alters after posterior correction. SUMMARY OF
      BACKGROUND DATA: The structural thoracolumbar or lumbar curve may change the
      local sagittal alignment thereby altering the sagittal balance in Lenke 5
      patients with AIS. However, few studies have evaluated the spinopelvic sagittal
      alignment before and after the surgery in these patients. METHODS: Forty-eight
      Lenke 5 patients with AIS who underwent posterior correction and fusion were
      included in this study. Preoperative and postoperative radiographs were reviewed
      measuring both the coronal and sagittal parameters. Three pelvic sagittal states
      (anteverted, normal, or retroverted) were evaluated according to the magnitude
      relationship of individual pelvic tilt with pelvic incidence (PI). Both the
      coronal and sagittal parameters between different pelvic sagittal states were
      compared. The alterations of these parameters by surgery would also be analyzed.
      RESULTS: The mean follow-up was 1.8 years. Preoperatively, the mean PI was 44.3
      degrees  with a pelvic tilt of 4.1 degrees . There was 48% patients showing the
      anteverted pelvis, whereas the remaining 52% showing normal. The patients with
      anteverted pelvis showed a smaller PI and more distal lower end vertebra than
      normal pelvis ones. Logistic regression analysis revealed PI (odds ratio [OR] =
      0.62, P = 0.024) and lower end vertebra (OR = 2.1, P = 0.037) were significantly
      associated with the risk of developing anteverted pelvis. The pelvic tilt was
      significantly increased and 61% of patients with preoperative anteverted pelvis
      had recovered. Logistic regression analysis revealed PI (OR = 0.7, P = 0.034) and
      lower instrumented vertebra (OR = 6.5, P = 0.002) were significantly associated
      with the risk of postoperative uncovered of anteverted pelvis. CONCLUSION:
      Anteverted pelvis appears in almost half of Lenke 5 patients with AIS, especially
      in who have smaller PI or distal lower end vertebra. The abnormal pelvic sagittal
      state will be generally corrected by posterior correction surgery except for
      patients with a PI less than 39 degrees  or a lower instrumented vertebra that
      extends to L5.

PMID- 25569528
TI  - Risk factors for surgical site infections after pediatric spine operations.
AB  - STUDY DESIGN: Matched case-control study. OBJECTIVE: To identify modifiable risk
      factors for surgical site infections (SSIs) after pediatric spinal fusion.
      SUMMARY OF BACKGROUND DATA: The number of SSIs after pediatric spinal fusions
      increased. METHODS: Between July 2001 and July 2010, 22 of 598 pediatric patients
      who underwent spinal fusion at a university hospital acquired SSIs. Each patient
      with an SSI was matched with 2 controls by procedure date. Bivariable and
      multivariable analyses were used to identify risk factors for SSIs and outcomes
      of SSIs. RESULTS: Gram-negative organisms caused more than 50% of the SSIs. By
      multivariable analysis, neuromuscular scoliosis (odds ratio [OR] = 20.8; 95%
      confidence interval [CI], 3.1-889.5; P < 0.0001) and weight-for-age at the 95th
      percentile or higher (OR = 8.6; 95% CI, 1.2-124.9; P = 0.02) were preoperative
      factors associated with SSIs. Blood loss (OR = 1.0; 95% CI, 1.0-1.0; P = 0.039)
      and allografts and allografts in combination with other grafts were operative
      risk factors for SSIs. The final overall risk model for SSIs was weight-for-age
      at the 95th percentile or higher (OR = 4.0; 95% CI, 1.4-infinity; P = 0.037),
      American Society of Anesthesiologists score 3 or more (OR = 3.8; 95% CI, 1.6
      infinity; P = 0.01), and prolonged operation duration (OR = 1.0/min increase; 95%
      CI, 1.0-1.0; P = 0.004). SSIs were associated with 2.8 days of additional
      postoperative length of stay (P = 0.02). Neuromuscular scoliosis was the only
      factor significantly associated with hospital readmission (OR = 23.6; 95% CI, 3.8
      147.3; P = 0.0007). CONCLUSION: Our results suggest that pediatric patients
      undergoing spinal fusion might benefit from antimicrobial prophylaxis that covers
      gram-negative organisms. Surgical duration, graft implantation, and blood loss
      are potentially modifiable operative risk factors. Neuromuscular scoliosis, high
      weight-for-age, and American Society of Anesthesiologists scores 3 or more may
      help surgical teams identify patients at high risk for SSI.

PMID- 25569529
TI  - Reducing radiation exposure during kyphoplasty with the use of a remote control
      injection system: a prospective study.
AB  - STUDY DESIGN: A prospective study. OBJECTIVE: To compare surgeons' radiation
      exposure during kyphoplasty with and without the use of a remote control
      injection system. SUMMARY OF BACKGROUND DATA: Distance from radiation sources is
      a critical factor for reducing radiation exposure during spine surgery. A newly
      designed device was used to minimize operators' radiation exposure during
      kyphoplasty. METHODS: Forty-four patients admitted for single-level osteoporotic
      vertebral compression fracture were randomly divided into 2 groups (groups A and
      B) and treated with kyphoplasty. The remote control injection system was used
      only in group B. The radiation doses to the surgeon's eyes, thyroid, chest, and
      right wrist were recorded with 4 unprotected radiometers simultaneously.
      Operation time, fluoroscopic time, cement amount, patient-reported pre- and
      postoperative visual analogue scale scores for pain, and complications were
      recorded. RESULTS: For group A, the radiation doses at the eyes, thyroid, and
      right wrist were 1.132 +/- 0.104 mSv, 0.647 +/- 0.049 mSv, 0.578 +/- 0.056 mSv,
      and 1.877 +/- 0.214 mSv, respectively; for Group B, these doses were 0.257 +/-
      0.067 mSv, 0.201 +/- 0.049 mSv, 0.145 +/- 0.033 mSv, and 0.353 +/- 0.046 mSv,
      respectively (P < 0.05). Comparisons of the radiation doses the chief surgeon and
      the resident surgeon received showed that the resident surgeon received more
      radiation during group A procedures; during group B procedures, the surgeons
      received similar doses. The proportion of average fluoroscopic time devoted to
      the bone cement injection step for groups A and B was 64% and 63%, respectively,
      and the average proportion of the radiation doses that were received during the
      bone cement injection step was 66% for group A and 36% for group B. Compared with
      the preoperative visual analogue scale score, the postoperative visual analogue
      scale score was significantly reduced in both groups. CONCLUSION: During
      kyphoplasty, the use of the remote control injection system can significantly
      reduce surgeons' radiation exposure without affecting the efficiency of
      procedures.

PMID- 25569533
TI  - Construction of cellulose based ZnO nanocomposite films with antibacterial
      properties through one-step coagulation.
AB  - Cellulose based ZnO nanocomposite (RCZ) films were prepared from cellulose
      carbamate-NaOH/ZnO solutions through one-step coagulation in Na2SO4 aqueous
      solutions. The structure and properties of RCZ films were characterized using
      XRD, FTIR, XPS, SEM, TEM, TG, tensile testing, and antibacterial activity tests.
      The content of ZnO in RCZ films was obtained in the range of 2.7-15.1 wt %. ZnO
      nanoparticles with a hexagonal wurtzite structure agglomerated into large
      particles, which firmly embedded in the cellulose matrix. RCZ films displayed
      good mechanical properties and high thermal stability. Moreover, the films
      exhibited excellent UV-blocking properties and antibacterial activities against
      Staphylococcus aureus and Escherichia coli. A dramatic reduction in viable
      bacteria was observed within 3 h of exposure, while all of the bacteria were
      killed within 6 h. This work provided a novel and simple pathway for the
      preparation of regenerated cellulose films with ZnO nanoparticles for application
      as functional biomaterials. 

PMID- 25569534
TI  - Ultrastructural Changes of Caudate Nucleus in Mice Chronically Treated with
      Manganese.
AB  - Manganese (Mn) is able to cross the blood-brain barrier and induces functional
      and structural alterations during the intoxication by this metal. Therefore, the
      effects of chronic administration of Mn in the caudate nucleus of mice were
      evaluated by electron microscopy. Male albino mice were injected
      intraperitoneally with MnCl2 (5 mg/kg/d) 5 d per week during 9 weeks. The control
      group received only 0.9% of NaCl solution. The caudate nuclei were extracted and
      subsequently processed to be observed on a conventional transmission electron
      microscope at 2, 4, 6, and 9 weeks after treatment. A high percentage of
      vacuolated and swollen mitochondria were found throughout all the analyzed
      periods. Myelin disarrangement and ultrastructural alterations related to edema
      were observed increased in Mn-treated mice at week 9. Granular degeneration of
      myelin at week 9 accompanied with deposition of electron dense granules in the
      neuropil was also observed. Edema in neuropil and glial cells was detected from
      week 2 to week 9 accompanied by swollen mitochondria. Neuronal bodies, synaptic
      terminals, and perivascular cells were found swollen. Decreased electron density
      in postsynaptic areas and decreased and dispersed synaptic vesicles in
      presynaptic areas were noted in Mn-treated animals. Some neurons from Mn-treated
      mice showed cisternae dilation of the Golgi apparatus. These results suggest that
      Mn-treatment produces structural alterations in the caudate nucleus that could be
      responsible for some of the neurotoxic effects of this metal. 

PMID- 25569531
TI  - A regulatory hierarchy controls the dynamic transcriptional response to extreme
      oxidative stress in archaea.
AB  - Networks of interacting transcription factors are central to the regulation of
      cellular responses to abiotic stress. Although the architecture of many such
      networks has been mapped, their dynamic function remains unclear. Here we address
      this challenge in archaea, microorganisms possessing transcription factors that
      resemble those of both eukaryotes and bacteria. Using genome-wide DNA binding
      location analysis integrated with gene expression and cell physiological data, we
      demonstrate that a bacterial-type transcription factor (TF), called RosR, and
      five TFIIB proteins, homologs of eukaryotic TFs, combinatorially regulate over
      100 target genes important for the response to extremely high levels of peroxide.
      These genes include 20 other transcription factors and oxidative damage repair
      genes. RosR promoter occupancy is surprisingly dynamic, with the pattern of
      target gene expression during the transition from rapid growth to stress
      correlating strongly with the pattern of dynamic binding. We conclude that a
      hierarchical regulatory network orchestrated by TFs of hybrid lineage enables
      dynamic response and survival under extreme stress in archaea. This raises
      questions regarding the evolutionary trajectory of gene networks in response to
      stress. 

PMID- 25569535
TI  - Lymphangioma of the foot mimicking melanoma: an uncommon case of a Chinese boy.
AB  - Lymphangioma in the extremities is rare, and mostly caused by obstruction of the
      lymphatic circulation. Remote hemorrhage may lead to the presentation of
      melanotic moles on the surface of the tumor, leading clinicians to confuse this
      benign lesion with a malignant tumor, such as melanoma. We present the case of a
      Chinese boy with a mass in the foot mimicking melanoma, who was eventually
      diagnosed with lymphangioma following a thorough diagnostic workup. Complete
      resection resulted in a curative outcome. 

PMID- 25569532
TI  - Interactions of chromatin context, binding site sequence content, and sequence
      evolution in stress-induced p53 occupancy and transactivation.
AB  - Cellular stresses activate the tumor suppressor p53 protein leading to selective
      binding to DNA response elements (REs) and gene transactivation from a large pool
      of potential p53 REs (p53REs). To elucidate how p53RE sequences and local
      chromatin context interact to affect p53 binding and gene transactivation, we
      mapped genome-wide binding localizations of p53 and H3K4me3 in untreated and
      doxorubicin (DXR)-treated human lymphoblastoid cells. We examined the
      relationships among p53 occupancy, gene expression, H3K4me3, chromatin
      accessibility (DNase 1 hypersensitivity, DHS), ENCODE chromatin states, p53RE
      sequence, and evolutionary conservation. We observed that the inducible
      expression of p53-regulated genes was associated with the steady-state chromatin
      status of the cell. Most highly inducible p53-regulated genes were suppressed at
      baseline and marked by repressive histone modifications or displayed CTCF
      binding. Comparison of p53RE sequences residing in different chromatin contexts
      demonstrated that weaker p53REs resided in open promoters, while stronger p53REs
      were located within enhancers and repressed chromatin. p53 occupancy was strongly
      correlated with similarity of the target DNA sequences to the p53RE consensus,
      but surprisingly, inversely correlated with pre-existing nucleosome accessibility
      (DHS) and evolutionary conservation at the p53RE. Occupancy by p53 of REs that
      overlapped transposable element (TE) repeats was significantly higher (p<10-7)
      and correlated with stronger p53RE sequences (p<10-110) relative to nonTE
      associated p53REs, particularly for MLT1H, LTR10B, and Mer61 TEs. However,
      binding at these elements was generally not associated with transactivation of
      adjacent genes. Occupied p53REs located in L2-like TEs were unique in displaying
      highly negative PhyloP scores (predicted fast-evolving) and being associated with
      altered H3K4me3 and DHS levels. These results underscore the systematic
      interaction between chromatin status and p53RE context in the induced
      transactivation response. This p53 regulated response appears to have been tuned
      via evolutionary processes that may have led to repression and/or utilization of
      p53REs originating from primate-specific transposon elements. 

PMID- 25569536
TI  - Postoperative pain and the use of ultrasound-guided regional analgesia in
      pediatric supracondylar humerus fractures.
AB  - A total of 230 children undergoing closed reduction and percutaneous pinning of
      supracondylar humerus fractures were analyzed retrospectively. Severe pain (score
      >= 7/10) was reported in 10% of general anesthesia-only patients in the
      postanesthesia care unit and in 28% of the 130 admitted patients. The 36 patients
      who received ultrasound-guided regional analgesia+general anesthesia had
      decreased intraoperative opioid consumption and postanesthesia care unit pain
      scores. After admission, pain scores and opioid consumption did not differ
      between fracture and anesthesia types. No patient developed compartment syndrome.
      Severe pain is frequent after closed reduction and percutaneous pinning of
      supracondylar humerus fractures. Further study of ultrasound-guided regional
      analgesia is needed.

PMID- 25569537
TI  - High recurrence of instability in adolescents playing contact sports after
      arthroscopic shoulder stabilization.
AB  - Sixty-one shoulders in 57 adolescents underwent primary arthroscopic shoulder
      stabilization for labral tears sustained during contact sports (all Stanmore type
      1). Mean follow-up was 22 months, mean age 16.8 (13-18) years. Postoperatively,
      the median subjective improvement was 90%, median VAS pain was 0 and mean Oxford
      Instability Score was 26.8. Sixty-one per cent returned to preinjury sporting
      level. A higher than expected proportion reported recurrent dislocation, with 15%
      followed up for 1 year and 31% for 4 years. Of these 11 requiring further
      surgery, 90% of redislocations occurred while playing rugby. Sex, type of sport,
      hyperlaxity and tear morphology were not significantly related to recurrence.
      Adolescents are at high risk for recurrence following arthroscopic stabilization.
      Patients should be counselled for the higher recurrence rate and consideration
      should be made for other aetiological factors such as returning to contact sports
      and joint hyperlaxity. 

PMID- 25569538
TI  - Re-defining Technical Reports.

PMID- 25569539
TI  - Startups tout commercially 3D-printed tissue for drug screening.

PMID- 25569540
TI  - A sense of immunity: scientists are detailing the immune system as never before.

PMID- 25569542
TI  - Biting back: vaccine efforts redoubled as rabies deadline looms.

PMID- 25569543
TI  - Aging platelets stimulate TPO production.

PMID- 25569544
TI  - Human CD4(+) T cells spontaneously detect somatic mutations in cancer cells.

PMID- 25569545
TI  - Regulation of glucose homeostasis using radiogenetics and magnetogenetics in
      mice.

PMID- 25569546
TI  - Notch signaling maintains T cell memories.

PMID- 25569547
TI  - Reliability and validity of the computerized Revised Token Test: comparison of
      reading and listening versions in persons with and without aphasia.
AB  - PURPOSE: This study assessed the reliability and validity of intermodality
      associations and differences in persons with aphasia (PWA) and healthy controls
      (HC) on a computerized listening and 3 reading versions of the Revised Token Test
      (RTT; McNeil & Prescott, 1978). METHOD: Thirty PWA and 30 HC completed the test
      versions, including a complete replication. Reading versions varied according to
      stimulus presentation method: (a) full-sentence presentation, (b) self-paced word
      by-word full-sentence construction, and (c) self-paced word-by-word presentation
      with each word removed with the onset of the next word. Participants also
      received tests of aphasia and reading severity. RESULTS: The listening version
      produced higher overall mean scores than each of the reading versions.
      Differences were small and within 1 standard error of measurement of each
      version. Overall score test-retest reliability among versions for PWA ranged from
      r=.89 to r=.97. Correlations between the listening and reading versions ranged
      from r=.79 to r=.85. All versions correlated highly with aphasia and reading
      severity. Correlations were generally low for the HC due to restricted
      variability. Factor analysis yielded a 2-factor solution for PWA and a single
      factor for HC. CONCLUSIONS: Intermodality differences were small, and all 4
      versions were reliable, concurrently valid, and sensitive to similar linguistic
      processing difficulties in PWA.

PMID- 25569548
TI  - Adding radiotherapy to hormone treatment improves survival in older men with
      prostate cancer.

PMID- 25569549
TI  - Finite element model prediction of pulmonary contusion in vehicle-to-vehicle
      simulations of real-world crashes.
AB  - OBJECTIVE: Pulmonary contusion (PC) is a common chest injury following motor
      vehicle crash (MVC). Because this injury has an inflammatory component, studying
      PC in living subjects is essential. Medical and vehicle data from the Crash
      Injury Research and Engineering Network (CIREN) database were utilized to examine
      pulmonary contusion in case occupants with known crash parameters. METHOD: The
      selected CIREN cases were simulated with vehicle finite element models (FEMs)
      with the Total HUman Model for Safety (THUMS) version 4 as the occupant. To match
      the CIREN crash parameters, vehicle simulations were iteratively improved to
      optimize maximum crush location and depth. Fifteen cases were successfully
      modeled with the simulated maximum crush matching the CIREN crush to within 10%.
      Following the simulations, stress and strain metrics for the elements within the
      lungs were calculated. These injury metrics were compared to patient imaging data
      to determine the best finite element predictor of pulmonary contusion. RESULTS:
      When the thresholds were evaluated using volumetric criteria, first principal
      strain was the metric with the least variation in the FEM prediction of PC.
      CONCLUSIONS: A preliminary threshold for maximum crush was calculated to predict
      a clinically significant volume of pulmonary contusion.

PMID- 25569553
TI  - Response to Dalal et al.

PMID- 25569554
TI  - ERRATUM: Comprehensive CFTR gene analysis of the French cystic fibrosis screened
      newborn cohort: implications for diagnosis, genetic counseling, and mutation
      specific therapy.

PMID- 25569550
TI  - Evaluation of the loop mediated isothermal DNA amplification (LAMP) kit for
      malaria diagnosis in P. vivax endemic settings of Colombia.
AB  - BACKGROUND: Most commonly used malaria diagnostic tests, including microscopy and
      antigen-detecting rapid tests, cannot reliably detect low-density infections
      which are frequent in low transmission settings. Molecular methods such as
      polymerase chain reaction (PCR) are highly sensitive but remain too laborious for
      field deployment. In this study, the applicability of a malaria diagnosis kit
      based on loop-mediated isothermal amplification (mLAMP) was assessed in malaria
      endemic areas of Colombia with Plasmodium vivax predominance.
      METHODOLOGY/PRINCIPAL FINDINGS: First, a passive case detection (PCD) study on
      278 febrile patients recruited in Tierralta (department of Cordoba) was conducted
      to assess the diagnostic performance of the mLAMP method. Second, an active case
      detection (ACD) study on 980 volunteers was conducted in 10 sentinel sites with
      different epidemiological profiles. Whole blood samples were processed for
      microscopic and mLAMP diagnosis. Additionally RT-PCR and nested RT-PCR were used
      as reference tests. In the PCD study, P. falciparum accounted for 23.9% and P.
      vivax for 76.1% of the infections and no cases of mixed-infections were
      identified. Microscopy sensitivity for P. falciparum and P. vivax were 100% and
      86.1%, respectively. mLAMP sensitivity for P. falciparum and P. vivax was 100%
      and 91.4%, respectively. In the ACD study, mLAMP detected 65 times more cases
      than microscopy. A high proportion (98.0%) of the infections detected by mLAMP
      was from volunteers without symptoms. CONCLUSIONS/SIGNIFICANCE: mLAMP sensitivity
      and specificity were comparable to RT-PCR. LAMP was significantly superior to
      microscopy and in P. vivax low-endemicity settings and under minimum
      infrastructure conditions, it displayed sensitivity and specificity similar to
      that of single-well RT-PCR for detection of both P. falciparum and P. vivax
      infections. Here, the dramatically increased detection of asymptomatic malaria
      infections by mLAMP demonstrates the usefulness of this new tool for diagnosis,
      surveillance, and screening in elimination strategies.

PMID- 25569555
TI  - CORRIGENDUM: A clinical appraisal of different Z-score equations for aortic root
      assessment in the diagnostic evaluation of Marfan syndrome.

PMID- 25569556
TI  - Different infectivity of HIV-1 strains is linked to number of envelope trimers
      required for entry.
AB  - HIV-1 enters target cells by virtue of envelope glycoprotein trimers that are
      incorporated at low density in the viral membrane. How many trimers are required
      to interact with target cell receptors to mediate virus entry, the HIV entry
      stoichiometry, still awaits clarification. Here, we provide estimates of the HIV
      entry stoichiometry utilizing a combined approach of experimental analyses and
      mathematical modeling. We demonstrate that divergent HIV strains differ in their
      stoichiometry of entry and require between 1 to 7 trimers, with most strains
      depending on 2 to 3 trimers to complete infection. Envelope modifications that
      perturb trimer structure lead to an increase in the entry stoichiometry, as did
      naturally occurring antibody or entry inhibitor escape mutations. Highlighting
      the physiological relevance of our findings, a high entry stoichiometry
      correlated with low virus infectivity and slow virus entry kinetics. The entry
      stoichiometry therefore directly influences HIV transmission, as trimer number
      requirements will dictate the infectivity of virus populations and efficacy of
      neutralizing antibodies. Thereby our results render consideration of
      stoichiometric concepts relevant for developing antibody-based vaccines and
      therapeutics against HIV. 

PMID- 25569557
TI  - A Review of Potential Marine-derived Hypotensive and Anti-obesity Peptides.
AB  - Bioactive peptides are food derived components, usually consisting of 3-20 amino
      acids, which are inactive when incorporated within their parent protein. Once
      liberated by enzymatic or chemical hydrolysis, during food processing and
      gastrointestinal transit, they can potentially provide an array of health
      benefits to the human body. Owing to an unprecedented increase in the worldwide
      incidence of obesity and hypertension, medical researchers are focusing on the
      hypotensive and anti-obesity properties of nutritionally derived bioactive
      peptides. The role of the renin-angiotensin system has long been established in
      the aetiology of metabolic diseases and hypertension. Targeting the renin
      angiotensin system by inhibiting the activity of angiotensin-converting enzyme
      (ACE) and preventing the formation of angiotensin II can be a potential
      therapeutic approach to the treatment of hypertension and obesity. Fish-derived
      proteins and peptides can potentially be excellent sources of bioactive
      components, mainly as a source of ACE inhibitors. However, increased use of
      marine sources, poses an unsustainable burden on particular fish stocks, so, the
      underutilized fish species and by-products can be exploited for this purpose.
      This paper provides an overview of the techniques involved in the production,
      isolation, purification, and characterization of bioactive peptides from marine
      sources, as well as the evaluation of the ACE inhibitory (ACE-I) activity and
      bioavailability.

PMID- 25569559
TI  - Unprecedented one-pot chemocontrolled entry to thioxoimidazolidinones and
      aminoimidazolones: synthesis of kinase inhibitor leucettamine B.
AB  - A novel and highly chemoselective protocol for the construction of
      thioxoimidazolidinone and aminoimidazolone frameworks was explored, and the
      influence of the reaction conditions on product formation was studied to
      establish two distinct approaches for their selective formation. In this one-pot
      reaction, ambient temperature generally resulted in the formation of
      thioxoimidazolidinones, whereas microwave irradiation provided aminoimidazolones
      exclusively. An attempt to elucidate the observed chemoselectivity is described,
      and the products were confirmed by X-ray studies. One-pot synthesis toward
      Leucettamine B, a marine alkaloid, was achieved on the basis of this protocol. 

PMID- 25569560
TI  - Increasing number of cancer survivors is putting pressure on NHS, says charity.

PMID- 25569558
TI  - Application of clinico-radiologic-pathologic diagnosis of diffuse parenchymal
      lung diseases in children in China.
AB  - Diffuse parenchymal lung diseases in children (chDPLD) or interstitial lung
      diseases in children (chILD) represent a heterogeneous group of respiratory
      disorders that are mostly chronic and associated with high morbidity and
      mortality. However, the incidence of chDPLD is so low that most pediatricians
      lack sufficient knowledge of chDPLD, especially in China. Based on the clinico
      radiologic-pathologic (CRP) diagnosis, we tried to describe (1) the
      characteristics of chDPLD and (2) the ratio of each constituent of chDPLD in
      China. Data were evaluated, including clinical, radiographic, and pathologic
      results from lung biopsies. We collected 25 cases of chDPLD, 18 boys and 7 girls
      with a median age of 6.0 years, from 16 hospitals in China. The most common
      manifestations included cough (n = 24), dyspnea (n = 21), and fever (n = 4).
      There were three cases of exposure-related interstitial lung disease (ILD), three
      cases of systemic disease-associated ILD, nineteen cases of alveolar structure
      disorder-associated ILD, and no cases of ILD specific to infancy. Non-specific
      interstitial pneumonia (n = 9) was the two largest groups. CONCLUSION: Non
      specific interstitial pneumonia is the main categories of chDPLD in China. Lung
      biopsy is always a crucial step in the final diagnosis. However, clinical and
      imaging studies should be carefully evaluated for their value in indicating a
      specific chDPLD.

PMID- 25569561
TI  - More dominant shear flow effect assisted by added carbon nanotubes on
      crystallization kinetics of isotactic polypropylene in nanocomposites.
AB  - More dominant shear flow effect with different shear rates and shear time with
      assistance of added carbon nanotubes (CNTs) of low amounts on the crystallization
      kinetics of isotactic polypropylene (iPP) in CNT/iPP nanocomposites was
      investigated by applying differential scanning calorimetry (DSC), polarized
      optical microscopy (POM), and rheometer. CNTs were chemically modified to improve
      the dispersity in the iPP matrix. CNT/iPP nanocomposites with different CNT
      contents were prepared by solution blending method. The crystallization kinetics
      for CNT/iPP nanocomposites under the quiescent condition studied by DSC indicates
      that the addition of CNTs of low amounts significantly accelerates
      crystallization of iPP due to heterogeneous nucleating effect of CNTs, whereas a
      saturation effect exists at above a critical CNT content. The shear-induced
      crystallization behaviors for CNT/iPP nanocomposites studied by POM and rheometry
      demonstrate the continuously accelerated crystallization kinetics with assistance
      from added CNTs, with increasing CNT content, shear rate, and shear time, without
      any saturation effect. The changes of nucleation density for CNT/iPP
      nanocomposites under different shear conditions can be quantified by using a
      space-filling modeling from the rheological measurements, and the results
      illustrate that the combined effects of added CNTs and shear flow on the
      acceleration of crystallization kinetics are not additive, but synergetic. The
      mechanisms for the synergetic effect of added CNTs and shear flow are provided. 

PMID- 25569563
TI  - Photoredox catalysts: synthesis of the bipyrazine ligand.
AB  - The bipyrazine ligand is often employed in photoredox catalysts in order to
      increase the excited state oxidation potential of the catalyst. However,
      literature syntheses of the ligand are cumbersome and typically lead to low
      yields. This hampers use of the desired catalysts. We report here an efficient
      copper based synthesis of the bipyrazine ligand that affords the product in 65
      76% yield on a multigram scale. 

PMID- 25569562
TI  - Metabolic responses to Orientia tsutsugamushi infection in a mouse model.
AB  - Tsutsugamushi disease is an infectious disease transmitted to humans through the
      bite of the Orientia tsutsugamushi-infected chigger mite; however, host-pathogen
      interactions and the precise mechanisms of damage in O. tsutsugamushi infections
      have not been fully elucidated. Here, we analyzed the global metabolic effects of
      O. tsutsugamushi infection on the host using 1H-NMR and UPLC-Q-TOF mass
      spectroscopy coupled with multivariate statistical analysis. In addition, the
      effect of O. tsutsugamushi infection on metabolite concentrations over time was
      analyzed by two-way ANOVAs. Orthogonal partial least squares-discriminant
      analysis (OPLS-DA) showed distinct metabolic patterns between control and O.
      tsutsugamushi-infected mice in liver, spleen, and serum samples. O. tsutsugamushi
      infection caused decreased energy production and deficiencies in both
      remethylation sources and glutathione. In addition, O. tsutsugamushi infection
      accelerated uncommon energy production pathways (i.e., excess fatty acid and
      protein oxidation) in host body. Infection resulted in an enlarged spleen with
      distinct phospholipid and amino acid characteristics. This study suggests that
      metabolite profiling of multiple organ tissues and serum could provide insight
      into global metabolic changes and mechanisms of pathology in O. tsutsugamushi
      infected hosts. 

PMID- 25569564
TI  - A novel soybean (Glycine max) gene encoding a family 3 beta-glucosidase has high
      isoflavone 7-O-glucoside-hydrolyzing activity in transgenic rice.
AB  - A previous study demonstrated that purified Glycine max beta-glucosidase (GmBGL)
      could hydrolyze glucosyl isoflavone to the aglyconic form. This study reports the
      cloning and functional characterization of a soybean cDNA encoding the beta
      glucosidase. GmBGL was isolated by use of a purified soybean N-terminal amino
      acid sequence and conserved sequences of beta-glucosidase genes from other
      plants. Sequence analysis of GmBGL revealed an open reading frame of 1884 bp
      encoding a polypeptide of 627 amino acids with a calculated molecular mass of 69
      kDa. Phylogenetic analysis classified the GmBGL into the glycosyl hydrolase 3
      family. In soybean, the GmBGL transcript was predominantly accumulated in roots
      and leaves. To examine the enzymatic activity and substrate specificity, GmBGL
      was ectopically expressed in transgenic rice. Purified GmBGL protein from
      transgenic rice could catalyze the hydrolysis of genistin and daidzin to produce
      genistein and daidzein, respectively, which confirmed GmBGL as a functional beta
      glucosidase with isoflavone glucoside-hydrolyzing activity. This paper reveals
      that GmBGL is a key enzyme in transforming glucosyl isoflavones to aglycones in
      soybean, which may help in genetic manipulation of aglycone-rich soybean seeds. 

PMID- 25569565
TI  - Enabling the (3 + 2) cycloaddition reaction in assembling newer anti-tubercular
      lead acting through the inhibition of the gyrase ATPase domain: lead optimization
      and structure activity profiling.
AB  - DNA gyrase, the sole type II topoisomerase present in Mycobacterium tuberculosis,
      is absent in humans and is a well validated target for anti-tubercular drug
      discovery. In this study, a moderately active inhibitor of Mycobacterium
      tuberculosis GyrB, the pharmaceutically unexploited domain of DNA gyrase, was
      reengineered using a combination of molecular docking and medicinal chemistry
      strategies to obtain a lead series displaying considerable in vitro enzyme
      efficacy and bacterial kill against the Mycobacterium tuberculosis H37Rv strain.
      Biophysical investigations using differential scanning fluorimetry experiments re
      ascertained the affinity of these molecules towards the GyrB domain. Furthermore,
      the molecules were completely devoid of hERG toxicity up to 30 MUM, as evaluated
      in a zebra fish model with a good selectivity index, and from a pharmaceutical
      point of view, turned out as potential candidates against TB. 

PMID- 25569566
TI  - Value of Adjusted Blood Requirement Index in determining failure to control bleed
      in patients with variceal bleeding.
AB  - INTRODUCTION: Variceal bleeding is a serious complication in patients with
      cirrhosis. Among the criteria that were proposed in Baveno conferences, the
      Adjusted Blood Requirement Index (ABRI) has not been validated prospectively in
      clinical practice. We therefore aim to evaluate the measurement of ABRI as a
      marker of failure to control bleeding and to evaluate the consistency of ABRI in
      relation to other criteria of failure to control variceal bleeding. PATIENTS AND
      METHODS: All patients with variceal bleeding who presented to Aga Khan University
      Hospital from January 2010 to December 2012 who were administered transfusion of
      packed red blood cells were included after obtaining informed consent. All
      patients were managed as per the standard protocol with intravenous terlipressin
      along with band ligation and injection of cyanoacrylate in cases of esophageal
      and fundal varices, respectively. Hemoglobin and hematocrit were measured every 6
      h for 48 h and then every 12 h until 5 days of index bleed in each patient.
      Packed cells were transfused if hemoglobin decreased below 8 g/dl. The number of
      blood units transfused, change in hemoglobin values, and ABRI were calculated
      after each unit of blood transfusion till 120 h. In patients in whom bleed could
      not be controlled, an ABRI value of 0.75 or more was compared with other Baveno
      IV-based parameters that define failure to control variceal bleeding. RESULTS:
      During the study period, 137 eligible patients with variceal bleed were admitted.
      The mean age of the patients was 52+/-12 years. The majority of patients (50.4%)
      were in Child-Pugh class B, followed by 38% in Child-Pugh class C. According to
      the Baveno IV criteria, overall failure to control acute variceal bleeding
      occurred in 52 (37.9%) patients. Excluding ABRI, failure to control bleeding was
      found in 22/137 (16%) patients, whereas ABRI-based criteria showed that in 34/137
      (24.8%) patients, bleeding could not be controlled. There were only four (2.9%)
      patients with variceal bleeding in whom ABRI and other additional Baveno IV-based
      criteria for failure to control bleeding were present. When ABRI was compared
      with other criteria for failure to control bleeding, it showed a sensitivity and
      specificity of 19 and 25%, respectively. CONCLUSION: This study showed that ABRI
      is not a useful additional tool to define failure to control bleeding after
      variceal hemorrhage in cirrhotic patients.

PMID- 25569567
TI  - Sarcopenia in liver cirrhosis: the role of computed tomography scan for the
      assessment of muscle mass compared with dual-energy X-ray absorptiometry and
      anthropometry.
AB  - BACKGROUND: Sarcopenia evaluated by computed tomography (CT) scan at the lumbar
      site has been identified as a risk factor for morbidity and mortality in
      cirrhosis. AIM: The aim of this study was to compare the measurement of muscle
      mass through CT scan, considered the gold standard, with other reliable
      techniques to evaluate the rate of agreement between different available methods
      for the assessment of muscle mass in cirrhosis. The correlation between
      measurements of muscle mass and of muscle strength was also investigated.
      PATIENTS AND METHODS: Adult patients eligible for liver transplantation were
      studied. Lumbar skeletal muscle cross-sectional area was measured by CT and
      muscle depletion was defined using previously published cut-offs. Mid-arm muscle
      circumference was calculated following anthropometric measures. The Fat-Free Mass
      Index and the Appendicular Skeletal Muscle Index were calculated using dual
      energy X-ray absorptiometry. Muscle strength was evaluated using the Hand Grip
      test. RESULTS: Fifty-nine patients with cirrhosis were included. Sarcopenia was
      diagnosed in 76% of the patients according to CT evaluation. A significant
      reduction in Fat-Free Mass Index and Appendicular Skeletal Muscle Index was
      observed in 42-52% of the patients, whereas 52% showed a mid-arm muscle
      circumference less than 10th percentile. Skeletal muscle mass evaluation through
      CT was only weakly correlated with dual-energy X-ray absorptiometry and
      anthropometry evaluation. No correlation was observed between CT measurement of
      muscle mass and Hand Grip test. CONCLUSION: CT scan can identify the highest
      percentage of sarcopenia in cirrhosis and no other techniques are actually
      available as a replacement. Future efforts should focus on approaches for
      assessing both skeletal muscle mass and function to provide a better evaluation
      of sarcopenia in cirrhotic patients.

PMID- 25569569
TI  - Therapeutic drug monitoring of infliximab in inflammatory bowel disease patients
      in a teaching hospital setting: results of a prospective cohort study.
AB  - OBJECTIVE: Therapeutic drug monitoring (TDM) of infliximab (IFX) is not routinely
      implemented in our clinical practice. We therefore carried out a prospective
      cohort study measuring IFX trough levels in our total inflammatory bowel disease
      (IBD) population in relation to remission. METHODS: Patient demographics, and
      medication and clinical history were collected from the electronic hospital
      information system. Blood was drawn at one time point for the determination of
      IFX trough levels and antibodies to IFX (ATI). Disease activity indices [Crohn's
      disease activity index (CDAI) and the Truelove-Witts disease activity index
      (TWDAI) for Crohn's disease and ulcerative colitis, respectively] and quality-of
      life scores (Visual Analog Scale) were obtained. RESULTS: We included 107
      patients. IFX levels varied from less than 0.02 to 21.9 MUg/ml. The median IFX
      level was 2.8 MUg/ml [interquartile range (IQR) 1.37-5.13]. The IFX level was
      associated significantly with remission (P=0.007). The median IFX level was 3.9
      MUg/ml (IQR 1.9-6.53) in patients in remission and 2.1 MUg/ml in patients with
      active disease (IQR 0.77-4.38) (P=0.074). Receiver operating charecteristic curve
      analysis indicated a cutoff value of 2.18 MUg/ml for CD and 6.26 MUg/ml for UC.
      Eleven patients (10.3%) had developed ATI. The appearance of ATI was associated
      with the disappearance of IFX [relative risk: 2.2 (95% confidence interval: 1.368
      3.610) P<0.0001], but not with relapse. The presence of ATI induced more infusion
      reactions [relative risk: 11.7 (95% confidence interval: 2.74-49.60) P<0.001].
      CONCLUSION: TDM of IFX in IBD outpatients in a teaching hospital setting showed
      large interindividual differences in IFX trough levels. Despite this, we still
      found a significant association between remission and IFX trough levels. We
      determined cutoff values for both IBD modalities. IFX trough levels were not
      detectable in a significant proportion of IBD patients; TDM is indicated to
      identify this group of patients.

PMID- 25569568
TI  - A 'cocoon immunization strategy' among patients with inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: A 'cocoon strategy' is defined as the strategy of protecting
      vulnerable patients from infectious diseases by vaccinating those in close
      contact with them. In our study, we evaluate the vaccination status among
      children living with patients with inflammatory bowel disease (IBD) to determine
      the realization of the cocoon strategy and to identify characteristics associated
      with pediatric vaccine refusal. PATIENTS AND METHODS: A self-completed survey was
      conducted on 136 hospitalized patients with IBD. The survey comprised questions
      about household child vaccination coverage, the reasons for vaccine refusal, and
      the history of infectious diseases among the patients. RESULTS: Fifty-six
      patients reported living with children. Forty percent of children were vaccinated
      with at least one of the recommended vaccines. Most frequently, children received
      pneumococcal (26%) and rotaviruses (22%) vaccines. The most common reason for
      nonimmunization was patients' opinion that immunizations are not necessary for
      them (52%). There was a statistically significant association between the
      nonreimbursed vaccines coverage and the educational level of the patients
      (P<0.0001). Despite the fact that 28% of the patients could not definitively
      recall varicella infection, none of them and none of the children in their
      household had been vaccinated against chickenpox. CONCLUSION: The use of
      nonmandatory vaccines recommended in family members of patients with IBD is
      insufficient. Further vaccine promotion and education of patients as well as
      their healthcare providers is required. A particular concern is associated with
      the pneumococcal, influenza, rotaviruses, and varicella infections. Nonimmunized
      and varicella-zoster virus-seronegative patients should be vaccinated, and in
      case of immunosuppression, vaccination of children in the household is required.

PMID- 25569570
TI  - Trimodal imaging endoscopy reduces the risk of synchronous gastric neoplasia.
AB  - BACKGROUND AND AIM: The accurate detection of synchronous neoplasia is important
      to reduce the risk of recurrence after endoscopic resection. Trimodal imaging
      endoscopy (TMIE) was developed for this purpose. Our aim was to compare the
      effects of TMIE and white-light imaging endoscopy (WLIE) in gastric neoplasia
      detection. PATIENTS AND METHODS: Six hundred and seventy-eight patients with
      gastric dysplasia or cancer initially treated by endoscopic resection and who
      underwent follow-up endoscopy were analyzed retrospectively. Gastric neoplasia
      detected within 1 year of endoscopic resection was defined as synchronous
      disease. WLIE or TMIE was used to detect another gastric neoplasia before
      endoscopic resection. RESULTS: Synchronous gastric neoplasia was observed in 41
      patients (6%), and occurred more frequently after the resection of carcinoma than
      dysplasia (8.5 vs. 4.6%, P=0.04). TMIE significantly reduced the frequency of
      synchronous gastric lesions than WLIE (2.3 vs. 9.3%, P<0.01). TMIE was more
      effective than WLIE in reducing the risk of missing a synchronous gastric lesion
      after adjusting for lesion multiplicity, experience, and resected lesion
      pathology (hazard ratio, 0.32; 95% confidence interval, 0.108-0.762). CONCLUSION:
      The risk of missing synchronous gastric neoplasia is higher after endoscopic
      resection for gastric cancer than dysplasia, but is reduced by TMIE. TMIE before
      endoscopic treatment can be useful in decreasing the risk of synchronous gastric
      neoplasia.

PMID- 25569571
TI  - Outcomes of initial medical compared with surgical strategies in the management
      of intra-abdominal abscesses in patients with Crohn's disease: a meta-analysis.
AB  - BACKGROUND: Several studies have also evaluated the efficacy of initial medical
      management compared with initial surgical management strategies with regard to
      abscess resolution with variable results. OBJECTIVE: The aim of this study is to
      evaluate the efficacy of initial medical management compared with surgical
      management of Crohn's disease (CD)-related intra-abdominal abscesses. DATA
      SOURCES: A comprehensive search of multiple databases (MEDLINE/PubMed, Cochrane
      databases, CINAHL, Scopus, and Google Scholar) was performed in August 2014.
      STUDY SELECTION: All studies on adults comparing initial surgical versus medical
      approaches to treat CD-related abscesses were included. MAIN OUTCOMES MEASURED:
      The durability of abscess resolution and rate of stoma creation between the
      groups undergoing initial surgical versus medical approaches were compared.
      RESULTS: The pooled analysis of the nine studies including a total 603 patients
      showed an overall rate of abscess resolution were 56.6% in the medical group
      compared with 80.7% in the surgical group. There was over three-fold higher
      chance of achieving abscess resolution when an initial surgical strategy was used
      at the time of abscess diagnosis compared with the medical strategy (odds ratio
      3.44, 95% confidence interval: 1.80, 6.58, P<0.001). The number needed to treat
      using the initial surgical approach to prevent a recurrent abscess was four
      patients. LIMITATIONS: All included studies were retrospective case series with
      potential clinical confounders not fully accounted in the analysis. CONCLUSION:
      Initial surgical management appears to be superior to medical management in
      patients with CD-related intra-abdominal abscesses. Though all the included
      studies in this meta-analysis were retrospective, this meta-analysis is likely
      the strongest level of evidence with regard to the management of CD-related
      abscesses, given that a randomized-control trial may not be feasible given the
      low rate of abscess development in CD.

PMID- 25569573
TI  - Newborns in England are screened for four extra genetic conditions.

PMID- 25569575
TI  - Polybrominated diphenyl ethers in surface soils near the Changwengluozha Glacier
      of Central Tibetan Plateau, China.
AB  - Forty-two congeners of polybrominated diphenyl ethers (PBDEs) were detected for
      each of 27 surface-soil samples collected at an area near the Changwengluozha
      Glacier in the Central Tibetan Plateau (CTP), a remote background area at
      altitude from 5080 to 5217 m. The total concentrations of BDEs in soils ranged
      from 15.3 to 248.0 ng/kg, which were found to be positively correlated with the
      clay contents in the soil. In addition to adsorption, the clay was found to serve
      as a catalyst for the debromination of PBDEs in soils. Three pieces of evidence
      confirmed that the clay was significantly correlated with the debrominating
      transformation from the higher brominated congeners to the less brominated
      congeners. The transforming rate was found to be increased 3.5% with a 10%
      increase in clays. Debromination is an important way for highly brominated
      congeners to transform into lighter brominated congeners that are more toxic.
      This study first provided the direct field evidences for clays contributing to
      the debromination of PBDEs, and elucidated the importance of it in PBDEs'
      environmental fate.

PMID- 25569574
TI  - Environmental waters and blaNDM-1 in Belgrade, Serbia: endemicity questioned.
AB  - New Delhi metallo-beta-lactamase-1 (NDM-1) will soon become the most commonly
      isolated and distributed metallo-beta-lactamase worldwide due to its rapid
      international dissemination and its ability to be expressed by numerous Gram
      negative pathogens. NDM-positive bacteria pose a significant public health threat
      in the Indian subcontinent and the Balkans, which have been designated as endemic
      regions. Our study was focused on urban rivers, a lake and springheads as a
      potential source of NDM-1-producing strains in Serbia, but also as a source of
      other metallo-beta-lactamases and extended-spectrum beta-lactamase (ESBL)
      producing bacteria. A total of 69 beta-lactam resistant isolates, belonging to 12
      bacterial genera, were collected from 8 out of 10 different locations in
      Belgrade, of which the most were from a popular recreational site, Ada Ciganlija
      Lake. Phenotypic tests revealed 7 (10.14%) ESBL-producing isolates and 39
      (56.52%) isolates resistant to imipenem, of which 32 were positive for metallo
      beta-lactamase (MBL) production. PCR and sequencing revealed the presence of
      genetic determinants for SHV (3 isolates), DHA-1 (1 isolate) and CMY-2 (1
      isolate) beta-lactamases. However, we did not detect any NDM-1-producing strains
      (previously described cases of NDM-1 from Serbia were limited to Belgrade), so we
      propose that Serbian NDM-1 is in fact a transplant and a nosocomial, rather than
      an environmental, issue and that Serbia is not an endemic region for NDM-1. 

PMID- 25569576
TI  - Environmental risk assessment of the Moroccan Atlantic continental shelf: the
      role of the industrial and urban area.
AB  - The present research presents the first large-scale analysis of heavy metal
      assessment in the Moroccan Atlantic shelf. This work provides scientific basis
      for future studies on environmental research and fills the gap in knowledge on
      the worldwide continental platforms. Metal distributions identified three
      different zones, mainly influenced by industrial and urban sewer (northern
      areas), agriculture runoffs (central zone), and estuarine discharges (southern
      areas), respectively. In the north part of the shelf, metal enrichments are
      observed near industrial and urban sewer mouths (Casablanca and Mohammedia
      cities). In the south and central areas, the probable absence of human impact on
      sediments is attributed to effective trapping in the estuary (Oum Er Rbia) and
      coastal zones, as well as dilution with less contaminated sediments and shelf
      sediments and removal with fine fractions due to estuary discharges. 

PMID- 25569572
TI  - Well-ordered trimeric HIV-1 subtype B and C soluble spike mimetics generated by
      negative selection display native-like properties.
AB  - The structure of BG505 gp140 SOSIP, a soluble mimic of the native HIV-1 envelope
      glycoprotein (Env), marks the beginning of new era in Env structure-based
      immunogen design. Displaying a well-ordered quaternary structure, these subtype A
      derived trimers display an excellent antigenic profile, discriminating
      recognition by broadly neutralizing antibodies (bNAbs) from non-broadly
      neutralizing antibodies (non-bNAbs), and provide a solid Env-based immunogenic
      platform starting point. Even with this important advance, obtaining homogeneous
      well-ordered soluble SOSIP trimers derived from other subtypes remains
      challenging. Here, we report the "rescue" of homogeneous well-ordered subtype B
      and C SOSIP trimers from a heterogeneous Env mixture using CD4 binding site
      directed (CD4bs) non-bNAbs in a negative-selection purification process. These
      non-bNAbs recognize the primary receptor CD4bs only on disordered trimers but not
      on the native Env spike or well-ordered soluble trimers due to steric hindrance.
      Following negative selection to remove disordered oligomers, we demonstrated
      recovery of well-ordered, homogeneous trimers by electron microscopy (EM). We
      obtained 3D EM reconstructions of unliganded trimers, as well as in complex with
      sCD4, a panel of CD4bs-directed bNAbs, and the cleavage-dependent, trimer
      specific bNAb, PGT151. Using bio-layer light interferometry (BLI) we demonstrated
      that the well-ordered trimers were efficiently recognized by bNAbs and poorly
      recognized by non-bNAbs, representing soluble mimics of the native viral spike.
      Biophysical characterization was consistent with the thermostability of a
      homogeneous species that could be further stabilized by specific bNAbs. This
      study revealed that Env trimers generate different frequencies of well-ordered
      versus disordered aberrant trimers even when they are genetically identical. By
      negatively selecting the native-like well-ordered trimers, we establish a new
      means to obtain soluble Env mimetics derived from subtypes B and C for expanded
      use as candidate vaccine immunogens. 

PMID- 25569577
TI  - Levels of polychlorinated dibenzodioxins and polychlorinated dibenzofurans in
      breast milk samples from three dioxin-contaminated hotspots of Vietnam.
AB  - We determined polychlorinated dibenzodioxin (PCDD) and polychlorinated
      dibenzofuran (PCDF) levels in breast milk of 143 primiparae living around the
      three most dioxin-contaminated areas of Vietnam. The women sampled lived in the
      vicinity of former U.S. air bases at Bien Hoa (n=51), Phu Cat (n=23), and Da Nang
      (n=69), which are known as dioxin hotspots. Breast milk samples from Bien Hoa
      City, where residents live very close to the air base, showed high levels of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with 18% of the samples containing >5
      pgTCDD/g lipid. However, Phu Cat residents lived far from the air base and their
      samples showed lower TCDD levels, with none containing >5 pgTCDD/g lipid. In Da
      Nang, TCDD levels in mothers from Thanh Khe (close to the air base, n=43) were
      significantly higher than those in mothers from Son Tra (far from the air base,
      n=26), but not other PCDD and PCDF (PCDD/F) congeners. Although TCDD levels in
      Bien Hoa were the highest among these hotspots, levels of other PCDD/F congeners
      as well as the geometric mean concentration of total PCDD/F level in Bien Hoa
      (9.3 pg toxic equivalents [TEQ]/g lipid) were significantly lower than the level
      observed in Phu Cat (14.1 pgTEQ/g lipid), Thanh Khe (14.3 pgTEQ/g lipid), and Son
      Tra (13.9 pgTEQ/g lipid). Our findings indicated that residents living close to
      former U.S. air bases were exposed to elevated levels of TCDD, but not of other
      PCDD/F congeners.

PMID- 25569578
TI  - Assessing element distribution and speciation in a stream at abandoned Pb-Zn
      mining site by combining classical, in-situ DGT and modelling approaches.
AB  - The distribution and speciation of elements along a stream subjected to
      neutralised acid mine drainage (NAMD) effluent waters (Matra Mountain, Hungary;
      Toka stream) were studied by a multi-methodological approach: dissolved and
      particulate fractions of elements were determined by HR-ICPMS, whereas speciation
      was carried out by DGT, supported by speciation modelling performed by Visual
      MINTEQ. Before the NAMD discharge, the Toka is considered as a pristine stream,
      with averages of dissolved concentrations of elements lower than world averages.
      A considerable increase of element concentrations caused by effluent water inflow
      is followed by a sharp or gradual concentration decrease. A large difference
      between total and dissolved concentrations was found for Fe, Al, Pb, Cu, Zn and
      As in effluent water and at the first downstream site, with high correlation
      factors between elements in particulate fraction, indicating their common
      behaviour, governed by the formation of ferri(hydr)oxides (co)precipitates. In
      situ speciation by the DGT technique revealed that Zn, Cd, Ni, Co, Mn and U were
      predominantly present as a labile, potentially bioavailable fraction (>90%). The
      formation of strong complexes with dissolved organic matter (DOM) resulted in a
      relatively low DGT-labile concentration of Cu (42%), while low DGT-labile
      concentrations of Fe (5%) and Pb (12%) were presumably caused by their existence
      in colloidal (particulate) fraction which is not accessible to DGT. Except for Fe
      and Pb, a very good agreement between DGT-labile concentrations and those
      predicted by the applied speciation model was obtained, with an average
      correlation factor of 0.96. This study showed that the in-situ DGT technique in
      combination with model-predicted speciation and classical analysis of samples
      could provide a reasonable set of data for the assessment of the water quality
      status (WQS), as well as for the more general study of overall behaviour of the
      elements in natural waters subjected to high element loads. 

PMID- 25569579
TI  - Pharmaceuticals' sorptions relative to properties of thirteen different soils.
AB  - Transport of human and veterinary pharmaceuticals in soils and consequent ground
      water contamination are influenced by many factors, including compound sorption
      on soil particles. Here we evaluate the sorption isotherms for 7 pharmaceuticals
      on 13 soils, described by Freundlich equations, and assess the impact of soil
      properties on various pharmaceuticals' sorption on soils. Sorption of ionizable
      pharmaceuticals was, in many cases, highly affected by soil pH. The sorption
      coefficient of sulfamethoxazole was negatively correlated to soil pH, and thus
      positively related to hydrolytic acidity and exchangeable acidity. Sorption
      coefficients for clindamycin and clarithromycin were positively related to soil
      pH and thus negatively related to hydrolytic acidity and exchangeable acidity,
      and positively related to base cation saturation. The sorption coefficients for
      the remaining pharmaceuticals (trimethoprim, metoprolol, atenolol, and
      carbamazepine) were also positively correlated with the base cation saturation
      and cation exchange capacity. Positive correlations between sorption coefficients
      and clay content were found for clindamycin, clarithromycin, atenolol, and
      metoprolol. Positive correlations between sorption coefficients and organic
      carbon content were obtained for trimethoprim and carbamazepine. Pedotransfer
      rules for predicting sorption coefficients of various pharmaceuticals included
      hydrolytic acidity (sulfamethoxazole), organic carbon content (trimethoprimand
      carbamazepine), base cation saturation (atenolol and metoprolol), exchangeable
      acidity and clay content (clindamycin), and soil active pH and clay content
      (clarithromycin). Pedotransfer rules, predicting the Freundlich sorption
      coefficients, could be applied for prediction of pharmaceutical mobility in soils
      with similar soil properties. Predicted sorption coefficients together with
      pharmaceutical half-lives and other imputes (e.g., soil-hydraulic, geological,
      hydro-geological, climatic) may be used for assessing potential ground-water
      contamination. 

PMID- 25569580
TI  - Desertification, salinization, and biotic homogenization in a dryland river
      ecosystem.
AB  - This study determined long-term changes in fish assemblages, river discharge,
      salinity, and local precipitation, and examined hydrological drivers of biotic
      homogenization in a dryland river ecosystem, the Trans-Pecos region of the Rio
      Grande/Rio Bravo del Norte (USA/Mexico). Historical (1977-1989) and current (2010
      2011) fish assemblages were analyzed by rarefaction analysis (species richness),
      nonmetric multidimensional scaling (composition/variability), multiresponse
      permutation procedures (composition), and paired t-test (variability). Trends in
      hydrological conditions (1970s-2010s) were examined by Kendall tau and quantile
      regression, and associations between streamflow and specific conductance
      (salinity) by generalized linear models. Since the 1970s, species richness and
      variability of fish assemblages decreased in the Rio Grande below the confluence
      with the Rio Conchos (Mexico), a major tributary, but not above it. There was
      increased representation of lower-flow/higher-salinity tolerant species, thus
      making fish communities below the confluence taxonomically and functionally more
      homogeneous to those above it. Unlike findings elsewhere, this biotic
      homogenization was due primarily to changes in the relative abundances of native
      species. While Rio Conchos discharge was>2-fold higher than Rio Grande discharge
      above their confluence, Rio Conchos discharge decreased during the study period
      causing Rio Grande discharge below the confluence to also decrease. Rio Conchos
      salinity is lower than Rio Grande salinity above their confluence and, as Rio
      Conchos discharge decreased, it caused Rio Grande salinity below the confluence
      to increase (reduced dilution). Trends in discharge did not correspond to trends
      in precipitation except at extreme-high (90th quantile) levels. In conclusion,
      decreasing discharge from the Rio Conchos has led to decreasing flow and
      increasing salinity in the Rio Grande below the confluence. This spatially uneven
      desertification and salinization of the Rio Grande has in turn led to a region
      wide homogenization of hydrological conditions and of taxonomic and functional
      attributes of fish assemblages. 

PMID- 25569582
TI  - Frequencies of heavy metal resistance are associated with land cover type in the
      Upper Mississippi River.
AB  - Taxonomic compositions of freshwater bacterial communities have been well
      characterized via metagenomic and amplicon-based approaches, especially next
      generation sequencing. However, functional diversity of these communities remains
      less well-studied. Various anthropogenic sources are known to impact the
      bacterial community composition in freshwater riverine systems and potentially
      alter functional diversity. In this study, high-throughput functional screening
      of large (~10,000 clones) fosmid libraries representing communities in the Upper
      Mississippi River revealed low frequencies of resistance to heavy metals in the
      following order: Mn2+>Cr3+>Zn2+>Cd2+>Hg2+. No resistance to Cu2+ was detected.
      Significant, but weak, correlations were observed between resistance frequencies
      of Cd and Cr with developed land cover (r2=0.08, P=0.016 and r=0.07, P=0.037,
      respectively). While discriminant function analyses further supported these
      associations, redundancy analysis further indicated associations with forested
      land cover and greater resistance to Hg and Zn. Nutrient and metal ion
      concentrations and abundances of bacterial orders were poorly correlated with
      heavy metal resistance, except for an association of Pseudomonadales abundance
      and resistance to Hg and Zn. Taken together, results of this study suggest that
      allochthonous bacteria contributed from specific land cover types influence the
      patterns of metal resistance throughout this river.

PMID- 25569583
TI  - Label-free DNA sensing platform with low-voltage electrolyte-gated transistors.
AB  - We report a method to measure DNA hybridization potentiometrically in a manner
      conducive to portable or hand-held biosensors. An electrolyte-gated transistor
      (EGT) based on poly(3-hexylthiophene) (P3HT) and an ion-gel serves as a
      transducer for surface hybridization of DNA. The key aspect of the design is the
      use of a floating-gate electrode functionalized with ssDNA whose potential is
      determined by both capacitive coupling with a primary, addressable gate electrode
      and the presence of adsorbed molecules. When DNA is hybridized at the floating
      gate, it offsets the primary gate voltage felt by the P3HT semiconductor; the
      offset is directly measurable and quantitatively related to the number density of
      dsDNA molecules. The presented sensing strategy can be readily adapted to other
      biomolecules of interest and integrated into a microfluidic system for field
      applications of biosensors. 

PMID- 25569581
TI  - Risk of DDT residue in maize consumed by infants as complementary diet in
      southwest Ethiopia.
AB  - Infants in Ethiopia are consuming food items such as maize as a complementary
      diet. However, this may expose infants to toxic contaminants like DDT. Maize
      samples were collected from the households visited during a consumption survey
      and from markets in Jimma zone, southwestern Ethiopia. The residues of total DDT
      and its metabolites were analyzed using the Quick, Easy, Cheap, Effective, Rugged
      and Safe (QuEChERS) method combined with dispersive solid phase extraction
      cleanup (d-SPE). Deterministic and probabilistic methods of analysis were applied
      to determine the consumer exposure of infants to total DDT. The results from the
      exposure assessment were compared with the health based guidance value in this
      case the provisional tolerable daily intake (PTDI). All maize samples (n=127)
      were contaminated by DDT, with a mean concentration of 1.770 mg/kg, which was far
      above the maximum residue limit (MRL). The mean and 97.5 percentile (P 97.5)
      estimated daily intake of total DDT for consumers were respectively 0.011 and
      0.309 mg/kg bw/day for deterministic and 0.011 and 0.083 mg/kg bw/day for
      probabilistic exposure assessment. For total infant population (consumers and non
      consumers), the 97.5 percentile estimated daily intake were 0.265 and 0.032 mg/kg
      bw/day from the deterministic and probabilistic exposure assessments,
      respectively. Health risk estimation revealed that, the mean and 97.5 percentile
      for consumers, and 97.5 percentile estimated daily intake of total DDT for total
      population were above the PTDI. Therefore, in Ethiopia, the use of maize as
      complementary food for infants may pose a health risk due to DDT residue.

PMID- 25569584
TI  - National Health and Nutrition Examination Survey: National Youth Fitness Survey
      Estimation Procedures, 2012.
AB  - BACKGROUND: The National Health and Nutrition Examination Survey's (NHANES)
      National Youth Fitness Survey (NNYFS) was conducted in 2012 by the Centers for
      Disease Control and Prevention's National Center for Health Statistics (NCHS).
      NNYFS collected data on physical activity and fitness levels to evaluate the
      health and fitness of children aged 3-15 in the United States. The survey
      comprised three levels of data collection: a household screening interview (or
      screener), an in-home personal interview, and a physical examination. The
      screener's primary objective was to determine whether any children in the
      household were eligible for the interview and examination. Eligibility was
      determined by preset selection probabilities for desired sex-age subdomains.
      After selection, the in-home personal interview collected demographic, health,
      physical activity, and nutrition information about the child as well as
      information about the household. The examination included physical measurements
      and fitness tests. OBJECTIVES: This report provides background on the NNYFS
      program and summarizes the survey's sample design specifications. The report
      presents NNYFS estimation procedures, including the methods used to calculate
      survey weights for the full sample as well as a combined NHANES/NNYFS sample for
      2012 (accessible only through the NCHS Research Data Center). The report also
      describes appropriate variance estimation methods. Documentation of the sample
      selection methods, survey content, data collection procedures, and methods to
      assess nonsampling errors are reported elsewhere.

PMID- 25569585
TI  - Advancements and challenges in computational biology.

PMID- 25569586
TI  - Crystallization of bifonazole and acetaminophen within the matrix of
      semicrystalline, PEO-PPO-PEO triblock copolymers.
AB  - The morphology and microstructure of crystalline drug/polymer solid dispersions
      could influence their physical stability and dissolution performance. In this
      study, the drug crystallization mechanism within PEG, PPG, and poloxamer matrix
      was investigated, and the resultant microstructure of various solid dispersions
      of acetaminophen (ACM) and bifonazole (BFZ) in the aforementioned polymers was
      characterized by differential scanning calorimetry (DSC), polarized optical
      microscopy (POM), and wide/small-angle X-ray diffraction (WAXD/SAXS). With a
      stronger molecular interaction with the PEG segments, ACM decreased the
      crystallization onset temperature and crystallinity of PEG and poloxamers much
      more than BFZ. The stronger molecular interaction and better miscibility between
      ACM and PEG also induced a more defective lamellar structure in the ACM solid
      dispersions compared with that in the BFZ systems, as revealed by DSC and SAXS
      investigation. Observed under polarized optical microscopy, PEG, PPG, and
      poloxamer could all significantly improve the crystallization rate of ACM and
      BFZ, because of the largely reduced Tg of the solid dispersions by these low Tg
      polymers. Moreover, when the drug loading was below 60%, crystallization of BFZ
      in PEG or poloxamer occurred preferably along the radial direction of PEG
      spherulite, rather than the perpendicular direction, which was attributed to the
      geometric restriction of well-ordered polymer lamellar structure in the BFZ solid
      dispersions. Similar phenomena were not observed in the ACM solid dispersions
      regardless of the drug loading, presumably because ACM could diffuse freely
      across the perpendicular direction of the PEG spherulite, through the well
      connected interlamellar or interfibrillar spaces produced by the defective PEG
      lamellar structure. The different drug-polymer interaction also caused a
      difference in the microstructure of polymer crystal, as well as a difference in
      drug distribution within the polymer matrix, which then synergistically
      facilitated a "confined crystallization" process to reduce the drug crystallite
      size below 100 nm. 

PMID- 25569587
TI  - Salinity from space unlocks satellite-based assessment of ocean acidification.

PMID- 25569588
TI  - Engineering adhesion to thermoresponsive substrates: effect of polymer
      composition on liquid-liquid-solid wetting.
AB  - Adhesion control in liquid-liquid-solid systems represents a challenge for
      applications ranging from self-cleaning to biocompatibility of engineered
      materials. By using responsive polymer chemistry and molecular self-assembly,
      adhesion at solid/liquid interfaces can be achieved and modulated by external
      stimuli. Here, we utilize thermosensitive polymeric materials based on random
      copolymers of di(ethylene glycol) methyl ether methacrylate (x = MEO2MA) and
      oligo(ethylene glycol) methyl ether methacrylate (y = OEGMA), that is, P(MEO2MAx
      co-OEGMAy), to investigate the role of hydrophobicity on the phenomenon of
      adhesion. The copolymer ratio (x/y) dictates macromolecular changes enabling
      control of the hydrophilic-to-lipophilic balance (HBL) of the polymer brushes
      through external triggers such as ionic strength and temperature. We discuss the
      HBL of the thermobrushes in terms of the surface energy of the substrate by
      measuring the contact angle at water-decane-P(MEO2MAx-co-OEGMAy) brush contact
      line as a function of polymer composition and temperature. Solid supported
      polyelectrolyte layers grafted with P(MEO2MAx-co-OEGMAy) display a transition in
      the wettability that is related to the lower critical solution temperature of the
      polymer brushes. Using experimental observation of the hydrophilic to hydrophobic
      transition by the contact angle, we extract the underlying energetics associated
      with liquid-liquid-solid adhesion as a function of the copolymer ratio. The
      change in cellular attachment on P(MEO2MAx-co-OEGMAy) substrates of variable
      (x/y) composition demonstrates the subtle role of compositional tuning on the
      ability to control liquid-liquid-solid adhesion in biological applications. 

PMID- 25569589
TI  - [Interview - Munich Institute impresses with "brace test"].

PMID- 25569590
TI  - [Motivator, supervisor, calming influence].

PMID- 25569592
TI  - [Dear readers].

PMID- 25569591
TI  - [Conservative therapy for metatarsal 5 basis fractures - retrospective and
      prospective analysis].
AB  - BACKGROUND: Approximately 30 % of all bone injuries are foot metatarsal
      fractures. Metatarsal V basis fractures occur most frequently. The classification
      is done into the tuberosity avulsion fractures, Jones fractures and stress
      fractures of the proximal diaphysis. The treatments of non-displaced fractures
      are generally conservative. The indication for surgical treatment depends on the
      load and the associated refracture rate. There are different types of treatment
      of these fractures. We present a possible approach to conservative treatments and
      show how different therapies affect healing of metatarsal V basis fractures and
      social reintegration of patients. METHODS: A retrospective study consisted of 68
      patients analysed during a 9-year period, whereas for a prospective analysis 18
      patients were included for a period of 3 years. The treatment was performed using
      either a splint, closed bandage of the ankle or special Gottinger Anklesplint
      bandage, with immediate pain-oriented full load in all groups. The subjective and
      objective treatment results were analysed accoding the Gottinger Phillips score.
      RESULTS: In retrospect, the fracture consolidation was observed after 8.1 weeks
      full load-bearing was achieved after 6.3 weeks on average. In the prospective
      analysis, the osseous consolidation occurred after 6.2 weeks, and the full load
      was applied after 1.7 weeks. After 10 weeks the treatment with the Anklesplint
      bandage was assessed with 105 points of a maximum 110 points of the Phillips
      score. The Anklesplint bandage was also the cheapest option in the cost
      comparison. CONCLUSION: Using the immobilisation of the metatarsal supination
      with the Anklesplint bandage the metatarsal V basis fractures can heal in a
      regular way. The functional outcome is better in comparison to the that with
      other treatments and it is a cost-effective treatment.

PMID- 25569593
TI  - Executive function and psychosocial adjustment in healthy children and
      adolescents: A latent variable modelling investigation.
AB  - The objective of this study was to establish latent executive function (EF) and
      psychosocial adjustment factor structure, to examine associations between EF and
      psychosocial adjustment, and to explore potential development differences in EF
      psychosocial adjustment associations in healthy children and adolescents. Using
      data from the multisite National Institutes of Health (NIH) magnetic resonance
      imaging (MRI) Study of Normal Brain Development, the current investigation
      examined latent associations between theoretically and empirically derived EF
      factors and emotional and behavioral adjustment measures in a large, nationally
      representative sample of children and adolescents (7-18 years old; N = 352).
      Confirmatory factor analysis (CFA) was the primary method of data analysis. CFA
      results revealed that, in the whole sample, the proposed five-factor model
      (Working Memory, Shifting, Verbal Fluency, Externalizing, and Internalizing)
      provided a close fit to the data, chi(2)(66) = 114.48, p < .001; RMSEA = .046;
      NNFI = .973; CFI = .980. Significant negative associations were demonstrated
      between Externalizing and both Working Memory and Verbal Fluency (p < .01)
      factors. A series of increasingly restrictive tests led to the rejection of the
      hypothesis of invariance, thereby precluding formal statistical examination of
      age-related differences in latent EF-psychosocial adjustment associations.
      Findings indicate that childhood EF skills are best conceptualized as a
      constellation of interconnected yet distinguishable cognitive self-regulatory
      skills. Individual differences in certain domains of EF track meaningfully and in
      expected directions with emotional and behavioral adjustment indices.
      Externalizing behaviors, in particular, are associated with latent Working Memory
      and Verbal Fluency factors.

PMID- 25569594
TI  - Non-leukodepleted red blood cell transfusion in sepsis patients: beyond
      oxygenation, is there a risk of inflammation?

PMID- 25569595
TI  - Diagnosis and Treatment of Cerebral Salt Wasting Syndrome With Cryptococcal
      Meningitis in HIV Patient.
AB  - Hyponatremia is one of the most common electrolyte imbalances in HIV patients.
      The differential diagnosis may include hypovolemic hyponatremia, syndrome of
      inappropriate antidiuretic hormone secretion (SIADH), and adrenal insufficiency.
      Here, we describe a case of hyponatremia secondary to cerebral salt wasting
      syndrome (CSWS) in an HIV patient with cryptococcal meningitis. A 52-year-old man
      with a history of diabetes and HIV was admitted for headache and found to have
      cryptococcal meningitis. He was also found to have asymptomatic hyponatremia. He
      had signs of hypovolemia, such as orthostatic hypotension, dry mucosa, decreased
      skin turgor, hemoconcentration, contraction alkalosis, and high BUN/Cr ratio. The
      laboratory findings revealed sodium of 125 mmol/L, potassium of 5.5 mmol/L, urine
      osmolality of 522 mOsm/kg, urine sodium of 162 mmol/L, and urine chloride of 162
      mmol/L. We started normal saline for hypovolemia, each 1 L prior and after
      amphotericin therapy. However, hypovolemia did not improve significantly despite
      IV fluid. Cosyntropin stimulation test was negative, and renin level was 0.25
      ng.mL.h, with the aldosterone level of <1 ng/dL, the serum brain natriuretic
      peptide of 15 pg/mL, and serum uric acid of 2.8 mg/dL. The diagnosis of CSWS was
      suspected, fludrocortisone was tried, and hypovolemia and hyponatremia improved.
      Cryptococcal meningitis in HIV patients can present with CSWS, and the
      distinction between CSWS and SIADH is important because the treatment for CSWS is
      different than that of SIADH. Both share a similar clinical picture except that
      CSWS presents with constant hypovolemia despite volume replacement. Salt tablets,
      normal saline, or fludrocortisone can be used for treatment. 

PMID- 25569596
TI  - Aortic Atherosclerosis: A Common Source of Cerebral Emboli, Often Overlooked!
AB  - Aortic atherosclerotic plaques are usually seen in males older than 55 years who
      are known to have risk factors of atherosclerosis. Recent large series of
      consecutive stroke patients reported that the prevalence of aortic atheromatous
      plaques in patients with stroke is about 21%-27%, which is in the same magnitude
      when compared with the prevalence of carotid disease (10%-13%) and atrial
      fibrillation (18%-30%). Atheromatous plaques are composed of a lipid pool, a
      fibrous cap, smooth muscle cells, and mononuclear cell infiltration with
      calcification. Aortic plaques can cause embolization to brain, extremities, or
      visceral organs. Atheroembolization can occur spontaneously or as a result of
      manipulation during cardiac or vascular surgery. Only few cases of cerebral
      embolization from an aortic plaque in the absence of any manipulation have been
      described. Although few atherosclerotic plaques can be visualized on the
      aortogram, transesophageal echocardiogram remains a preferred modality for
      diagnosis in such cases. We present a case of cerebral embolism arising from a
      mobile noncalcified complex aortic arch plaque diagnosed on a transesophageal
      echocardiogram and review the literature on its diagnosis, clinical implications,
      and management. 

PMID- 25569597
TI  - Sirolimus Versus Tacrolimus as Primary Immunosuppressant After Renal
      Transplantation: A Meta-Analysis and Economics Evaluation.
AB  - Sirolimus and tacrolimus are the major immunosuppressants for renal
      transplantation. Several studies have compared these 2 drugs, but the outcomes
      were not consistent. The aim of this study was to evaluate the efficacy, safety,
      and pharmacoeconomics of sirolimus and tacrolimus in the treatment of renal
      transplantation and provide evidence for the selection of essential drugs. Trials
      were identified through a computerized literature search of PubMed, EMBASE,
      Cochrane controlled trials register, Cochrane Renal Group Specialized Register of
      randomized controlled trials, and Chinese Biomedical database. Two independent
      reviewers assessed trials for eligibility and quality and then extracted data.
      Data were extracted for patient and graft mortality, acute rejection (AR), and
      adverse events. Dichotomous outcomes were reported as relative risk with 95%
      confidence intervals. A decision tree model was populated with data from a
      literature review and used to estimate costs and QALYs gained and incremental
      cost-effectiveness. Altogether, 1189 patients from 8 randomized controlled trials
      were included. The results of our analysis were that tacrolimus reduced the risks
      after renal transplantation of AR and patient withdrawn. Nevertheless, tacrolimus
      increased the risk of infection. Pharmacoeconomic analysis showed that tacrolimus
      represented a more cost-effective treatment than does cyclosporine for the
      prevention of adverse events after renal transplant. Tacrolimus is an effective
      and safe immunosuppressive agent, and it may be more cost-effective than
      cyclosporine for the primary prevention of AR in renal transplant recipients.
      However, it should be noted that such superiority was reversal when the cost of
      sirolimus and tacrolimus changed.

PMID- 25569598
TI  - Sequential Therapy or Standard Triple Therapy for Helicobacter pylori Infection:
      An Updated Systematic Review.
AB  - The effectiveness of standard triple therapy (STT) for the eradication of
      Helicobacter pylori has decreased recently. Sequential therapy (SQT) is a new
      regimen proposed to address this problem. The aim of this study was to compare
      the efficacy of SQT versus STT for H. pylori eradication. We searched The
      Cochrane Library, MEDLINE, Web of Science, and EMBASE databases up to July 2014.
      The risk ratios (RRs) of eradication rate were pooled, with a 95% confidence
      interval (CI). Thirty-six randomized clinical trials including a total of 10,316
      patients met the inclusion criteria. The RR for eradication of H. pylori with SQT
      compared with STT was 1.14 (95% CI: 1.09-1.17), the eradication rates were 84.1%
      and 75.1%, respectively. There was significant heterogeneity between trial
      results (I = 73%; P < 0.00001). Subgroup analyses showed that SQT was superior to
      both 7- and 10-day STT, but not significantly better than 14-day STT. This
      superiority existed when patients were treated with either metronidazole or
      tinidazole. Patients with single clarithromycin-resistant strain showed a greater
      benefit of SQT over STT (eradication rates 80.9% vs. 40.7%), RR = 1.98 (95% CI:
      1.33-2.94). There was no significant difference between groups in terms of the
      risk of adverse effects. In conclusion, SQT is more efficacious than STT (7 days
      and 10 days) in the eradication of HP, but the pooled rate seemed suboptimal.
      Further research is needed to develop more effective therapeutic approaches.
      Surveillance of resistance rates should be performed to guide treatment. 

PMID- 25569599
TI  - In situ carbon-coated yolk-shell V2O3 microspheres for lithium-ion batteries.
AB  - Metal oxide-based materials with yolk-shell morphology have been intensively
      investigated as important anodes for Li-ion batteries due to their large ion
      storage ability, high safety, and excellent cycling stability. In this work, in
      situ carbon-coated yolk-shell V2O3 microspheres were synthesized via a template
      free polyol solvothermal method. The growth of yolk-shell microspheres underwent
      coordination and polymerization, followed by an inside-out Ostwald-ripening
      process and further calcination in N2 atmosphere. The thin amorphous carbon
      layers coating on the microspheres' surface came from polyol frameworks which
      could protect V2O3 during the charge-discharge process and led to a better
      stability in Li-ion batteries. The in situ carbon-coated yolk-shell V2O3
      microspheres showed a capacity of 437.5 mAh.g(-1) after 100 cycles at a current
      density of 0.1 A.g(-1), which was 92.6% of its initial capability (472.5 mAh.g(
      1)). They were regarded as excellent electrode materials for lithium-ion
      batteries and exhibit good electrochemistry performance and stability. 

PMID- 25569600
TI  - Serum galactomannan screening for diagnosis of invasive pulmonary aspergillosis
      in children after stem cell transplantation or with high-risk leukemia.
AB  - Both transplanted and leukemia patients are at high risk (HR) for invasive
      pulmonary aspergillosis (IPA). Methods for rapid diagnosis are crucial. Our
      objective was to investigate the impact of serial serum galactomannan assay (GMA)
      screening on IPA diagnosis in children. Between January 2010 and December 2011,
      all children following stem cell transplantation (SCT) or with HR leukemia were
      prospectively included. Serum samples for GMA were taken once-twice weekly.
      Results >.5 were considered positive. Patients suspected of having IPA were
      stratified as possible, probable, and definite. Forty-six children (median age, 8
      years) were included, 38 after SCT (32 allogeneic), 8 with HR leukemia. A total
      of 510 samples were taken; screening period was 1-6 months for 34 patients. GMA
      was negative in 28 patients, all but one without suspicion of IPA. Eighteen
      patients had positive GMA: while four (22%) were upgraded to probable IPA,
      fourteen (78%) were considered as false positives (FP), some associated with
      piperacillin-tazobactam treatment. GMA sensitivity and specificity were 0.8 and
      0.66, respectively; positive- and negative-predictive values (PPV, NPV) were 0.22
      and 0.96, respectively. GMA may have a role in evaluating HR children for IPA.
      Both NPV and FP rates are high. The cost benefit of early detection versus over
      diagnosis should be further studied.

PMID- 25569602
TI  - A case of bilateral, multiple, symmetric, concentric ring-shaped opacities in the
      cornea.

PMID- 25569604
TI  - Heparin induced thrombocytopenia.

PMID- 25569603
TI  - Usability and reliability of a remotely administered adult autism assessment, the
      autism diagnostic observation schedule (ADOS) module 4.
AB  - INTRODUCTION: The Autism Diagnostic Observation Schedule (ADOS) Module 4 is an
      autism assessment designed for verbally fluent adolescents and adults. Because of
      a shortage of available clinical expertise, it can be difficult for adults to
      receive a proper autism spectrum disorder (ASD) diagnostic assessment. A
      potential option to address this shortage is remote assessment. The objective of
      this study was to examine the feasibility, usability, and reliability of
      administering the ADOS Module 4 remotely using the Versatile and Integrated
      System for Telerehabilitation (VISYTER). MATERIALS AND METHODS: VISYTER consists
      of computer stations at the client site and clinician site for video
      communication and a Web portal for managing and coordinating the assessment
      process. Twenty-three adults with an ASD diagnosis participated in a within
      subject crossover design study in which both a remote ADOS and a face-to-face
      ADOS were administered. After completing the remote ADOS, participants completed
      a satisfaction survey. RESULTS: Participant satisfaction with the remote ADOS
      delivery system was high. The kappa value was greater than 0.61 on 21 of 31 ADOS
      items. There was substantial agreement on ADOS classification (i.e., diagnosis)
      between assessments delivered face-to-face versus assessments delivered remotely
      (interclass coefficient=0.92). Non-agreement may have been due to outside factors
      or practice effect despite a washout period. CONCLUSIONS: The results of this
      study demonstrate that an autism assessment designed to be delivered face to face
      can be administered remotely using an integrated Web-based system with high
      levels of usability and reliability.

PMID- 25569601
TI  - Discrimination of closely related species in tintinnid ciliates: new insights on
      crypticity and polymorphism in the genus Helicostomella.
AB  - This study focuses on the utility of molecular markers for the discrimination of
      closely related species in tintinnid ciliates. We analyzed the ecologically
      important genus Helicostomella by sequencing part of the large-subunit rDNA (LSU
      rDNA) and the 5.8S rDNA combined with the internally transcribed spacer regions 1
      and 2 (5.8S rDNA-ITS) from forty-five individuals collected in NW and SW Atlantic
      waters and after culturing. Although all described Helicostomella species
      represent a continuum of morphologies, forms with shorter or longer loricae would
      correspond to different species according to previous molecular data. Here we
      observed that long forms show both crypticity (i.e. two almost identical long
      forms with different DNA sequences) and polymorphism (i.e. some long forms
      develop significantly shorter loricae after culturing). Reviewing all available
      tintinnid sequences, we found that 1) three Helicostomella clusters are
      consistent with different species from a molecular perspective, although these
      clusters are neither clearly differentiated by their loricae nor unambiguously
      linked to described species, 2) Helicostomella is closely related (probably to
      the family or genus level) to four "Tintinnopsis-like" morphospecies, and 3) if
      considered separately, neither LSU rDNA nor 5.8S rDNA-ITS completely discriminate
      closely related species, thus supporting the use of multi-gene barcodes for
      tintinnids. 

PMID- 25569605
TI  - Role of water in stabilizing ferricyanide trianion and ion-induced effects to the
      hydrogen-bonding water network at long distance.
AB  - Structures and reactivities of gaseous Fe(CN)(6)(3-)(H(2)O)n were investigated
      using infrared photodissociation (IRPD) kinetics, spectroscopy, and computational
      chemistry in order to gain insights into how water stabilizes highly charged
      anions. Fe(CN)(6)(3-)(H(2)O)(8) is the smallest hydrated cluster produced by
      electrospray ionization, and blackbody infrared dissociation of this ion results
      in loss of an electron and formation of smaller dianion clusters. Fe(CN)(6)(3
      )(H(2)O)(7) is produced by the higher activation conditions of IRPD, and this ion
      dissociates both by loss of an electron and by loss of a water molecule.
      Comparisons of IRPD spectra to those of computed low-energy structures for
      Fe(CN)(6)(3-)(H(2)O)(8) indicate that water molecules either form two hydrogen
      bonds to the trianion or form one hydrogen bond to the ion and one to another
      water molecule. Magic numbers are observed for Fe(CN)(6)(3-)(H(2)O)n for n
      between 58 and 60, and the IRPD spectrum of the n = 60 cluster shows stronger
      water molecule hydrogen-bonding than that of the n = 61 cluster, consistent with
      the significantly higher stability of the former. Remarkably, neither cluster has
      a band corresponding to a free O-H stretch, and this band is not observed for
      clusters until n >= 70, indicating that this trianion significantly affects the
      hydrogen-bonding network of water molecules well beyond the second and even third
      solvation shells. These results provide new insights into the role of water in
      stabilizing high-valency anions and how these ions can pattern the structure of
      water even at long distances.

PMID- 25569607
TI  - Tactile warning signals for in-vehicle systems.
AB  - The last few years have seen growing interest in the design of tactile warning
      signals to direct driver attention to potentially dangerous road situations (e.g.
      an impending crash) so that they can initiate an avoidance maneuver in a timely
      manner. In this review, we highlight the potential uses of such warning signals
      for future collision warning systems and compare them with more traditional
      visual and auditory warnings. Basic tactile warning signals are capable of
      promoting driver alertness, which has been demonstrated to be beneficial for
      forward collision avoidance (when compared to a no warning baseline condition).
      However, beyond their basic alerting function, directional tactile warning
      signals are now increasingly being utilized to shift the attention of the driver
      toward locations of interest, and thus to further facilitate their speeded
      responses to potential collision events. Currently, many researchers are focusing
      their efforts on the development of meaningful (iconic) tactile warning signals.
      For instance, dynamic tactile warnings (varying in their intensity and/or
      location) can potentially be used to convey meaningful information to drivers.
      Finally, we highlight the future research that will be needed in order to explore
      how to present multiple directional warnings using dynamic tactile cues, thus
      forming an integrated collision avoidance system for future in-vehicle use. 

PMID- 25569606
TI  - Invasive Salmonella Typhimurium ST313 with naturally attenuated flagellin elicits
      reduced inflammation and replicates within macrophages.
AB  - Invasive non-typhoidal Salmonella (iNTS) are an important cause of septicemia in
      children under the age of five years in sub-Saharan Africa. A novel genotype of
      Salmonella enterica subsp. enterica serovar Typhimurium (multi-locus sequence
      type [ST] 313) circulating in this geographic region is genetically different to
      from S. Typhimurium ST19 strains that are common throughout the rest of the
      world. S. Typhimurium ST313 strains have acquired pseudogenes and genetic
      deletions and appear to be evolving to become more like the typhoidal serovars S.
      Typhi and S. Paratyphi A. Epidemiological and clinical data show that S.
      Typhimurium ST313 strains are clinically associated with invasive systemic
      disease (bacteremia, septicemia, meningitis) rather than with gastroenteritis.
      The current work summarizes investigations of the broad hypothesis that S.
      Typhimurium ST313 isolates from Mali, West Africa, will behave differently from
      ST19 isolates in various in vitro assays. Here, we show that strains of the ST313
      genotype are phagocytosed more efficiently and are highly resistant to killing by
      macrophage cell lines and primary mouse and human macrophages compared to ST19
      strains. S. Typhimurium ST313 strains survived and replicated within different
      macrophages. Infection of macrophages with S. Typhimurium ST19 strains resulted
      in increased apoptosis and higher production of proinflammatory cytokines, as
      measured by gene expression and protein production, compared to S. Typhimurium
      ST313 strains. This difference in proinflammatory cytokine production and cell
      death between S. Typhimurium ST19 and ST313 strains could be explained, in part,
      by an increased production of flagellin by ST19 strains. These observations
      provide further evidence that S. Typhimurium ST313 strains are phenotypically
      different to ST19 strains and instead share similar pathogenic characteristics
      with typhoidal Salmonella serovars. 

PMID- 25569608
TI  - Vector research addressing country control needs.

PMID- 25569609
TI  - The impact of pecuniary and non-pecuniary incentives for attracting young doctors
      to rural general practice.
AB  - Shortages of GPs in rural areas constitute a profound health policy issue
      worldwide. The evidence for the effectiveness of various incentives schemes,
      which can be specifically implemented to boost recruitment to rural general
      practice, is generally considered to be poor. This paper investigates young
      doctors' preferences for key job attributes in general practice (GP),
      particularly concerning location and income, using a discrete choice experiment
      (DCE). The subjects were all final year medical students and interns in Norway (N
      = 1562), of which 831 (53%) agreed to participate in the DCE. Data was collected
      in November-December 2010. Policy simulations were conducted to assess the
      potential impact of various initiatives that can be used to attract young doctors
      to rural areas. Most interestingly, the simulations highlight the need to
      consider joint policy programs containing several incentives if the policies are
      to have a sufficient impact on the motivation and likelihood to work in rural
      areas. Furthermore, we find that increased income seem to have less impact as
      compared to improvements in the non-pecuniary attributes. Our results should be
      of interest to policy makers in countries with publicly financed GP systems that
      may struggle with the recruitment of GPs in rural areas.

PMID- 25569610
TI  - Incentives for breastfeeding and for smoking cessation in pregnancy: an
      exploration of types and meanings.
AB  - Financial or tangible incentives are a strategy for improving health behaviours.
      The mechanisms of action of incentives are complex and debated. Using a
      multidisciplinary integrated mixed methods study, with service-user collaboration
      throughout, we developed a typology of incentives and their meanings for
      initiating and sustaining smoking cessation in pregnancy and breastfeeding. The
      ultimate aim was to inform incentive intervention design by providing insights
      into incentive acceptability and mechanisms of action. Systematic evidence
      syntheses of incentive intervention studies for smoking cessation in pregnancy or
      breastfeeding identified incentive characteristics, which were developed into
      initial categories. Little published qualitative data on user perspectives and
      acceptability was available. Qualitative interviews and focus groups conducted in
      three UK regions with a diverse socio-demographic sample of 88 women and
      significant others from the target population, 53 service providers, 24
      experts/decision makers, and conference attendees identified new potential
      incentives and providers, with and without experience of incentives. Identified
      incentives (published and emergent) were classified into eight categories: cash
      and shopping vouchers, maternal wellbeing, baby and pregnancy-related, behaviour
      related, health-related, general utility, awards and certificates, and
      experiences. A typology was refined iteratively through concurrent data
      collection and thematic analysis to explore participants' understandings of
      'incentives' and to compare and contrast meanings across types. Our typology can
      be understood in three dimensions: the degree of restriction, the extent to which
      each is hedonic and/or utilitarian, and whether each has solely monetary value
      versus monetary with added social value. The layers of autonomy, meanings and the
      social value of incentive types influence their acceptability and interact with
      structural, social, and personal factors. Dimensions of incentive meaning that go
      beyond the simple incentive description should inform incentive programme design
      and are likely to influence outcomes. 

PMID- 25569611
TI  - Elimination of influences of the ACTN3 R577X variant on oxygen uptake by
      endurance training in healthy individuals.
AB  - AIM: To study the relationship between the ACTN3 R577X polymorphism and oxygen
      uptake (VO2) before and after exercise training. METHODS: Police recruits (N=206,
      25+/-4 y) with RR (n=75), RX (n=97), and XX (n=33) genotypes were selected. After
      baseline measures, they underwent 18 wk of running endurance training. Peak VO2
      was obtained by cardiopulmonary exercise testing. RESULTS: Baseline body weight
      was not different among genotypes. At baseline, XX individuals displayed higher
      VO2 at anaerobic threshold, respiratory compensation point, and exercise peak
      than did RR individuals (P<.003). Endurance training significantly increased VO2
      at anaerobic threshold, respiratory compensation point, and exercise peak
      (P<2*10(-6)), but the differences between XX and RR were no longer observed. Only
      relative peak VO2 exercise remained higher in XX than in RR genotype (P=.04). In
      contrast, the increase in relative peak VO2 was greater in RR than in XX
      individuals (12% vs 6%; P=.02). CONCLUSION: ACTN3 R577X polymorphism is
      associated with VO2. XX individuals have greater aerobic capacity. Endurance
      training eliminates differences in peak VO2 between XX and RR individuals. These
      findings suggest a ceiling-effect phenomenon, and, perhaps, trained individuals
      may not constitute an adequate population to explain associations between
      phenotypic variability and gene variations.

PMID- 25569613
TI  - Development of the combat distress scale of the Combat Experiences Questionnaire
      (CEQ).
AB  - BACKGROUND: Military combat exposure can be perceived as a great threat to the
      integrity of soldiers. However, no available assessment tools evaluate the degree
      of emotional distress that results from the exposure to various combat scenarios.
      This paper presents the second independent section of the Combat Exposure
      Questionnaire, the Combat Distress Scale (CEQ B). This questionnaire assesses
      Veterans' subjective emotional distress that is due to objective and typical
      military combat scenarios during war. METHODS: A sample of 708 Portuguese
      Overseas War Veterans participated. The scale structure of the CEQ B was analyzed
      with a Rasch Model, and the internal consistency and convergent validity of the
      scale were studied. The temporal reliability was calculated in a subgroup of 112
      participants. Two samples of war Veterans with and without war-related Post
      Traumatic Stress Disorder (N=40 and N=47, respectively) were used to explore the
      scale's discriminant validity. RESULTS: Overall, the CEQ B showed an acceptable
      fit to the data, excellent internal consistency, high temporal stability,
      adequate convergent validity and suitable discriminant validity. LIMITATIONS:
      This study used a population of male war Veterans that did not equally represent
      genders or the full adult age span, which may hinder the generalization of the
      results. CONCLUSION: The findings indicated that the CEQ B is valid, reliable and
      supported by convergent and discriminant data. This lends confidence in the use
      of the measure as an assessment of the subjective emotional distress resulting
      from exposure to military combat scenarios in clinical and research settings.

PMID- 25569612
TI  - Trajectories of depressive symptoms during the transition to young adulthood: the
      role of chronic illness.
AB  - BACKGROUND: Little is known about the natural course of depressive symptoms among
      youth with chronic illness during their transition from adolescence to young
      adulthood. METHODS: A representative epidemiological sample of 2825 youth aged 10
      11 years from the National Longitudinal Survey of Children and Youth were
      followed until 24-25 years of age. Presence of chronic illness was measured using
      self-report and symptoms of depression were assessed using the Center for
      Epidemiological Studies Depression Scale. Multilevel modeling was used to
      investigate trajectories of depressive symptoms, adjusting for family environment
      and sociodemographic characteristics during the transition to young adulthood.
      RESULTS: Trajectories showed cubic change over time - increasing from early to
      mid-adolescence, decreasing to early young adulthood, increasing again to late
      young adulthood. Youth with chronic illness (n=753) had significantly less
      favorable trajectories and significantly higher proportions of clinically
      relevant depressive symptoms over time compared to their peers without chronic
      illness (n=2072). LIMITATIONS: This study is limited by selective attrition, self
      reported chronic illness and no assessment of illness severity, and mediating
      effects of family environment factors could not be examined. CONCLUSIONS:
      Findings support the diathesis-stress model; chronic illness negatively
      influenced depressive symptoms trajectories, such that youth with chronic illness
      had higher depression scores and less favorable trajectories over time. The
      health and school system are uniquely positioned to support youth with chronic
      illness navigate this developmental period in an effort to prevent declines in
      mental health.

PMID- 25569614
TI  - RecFOR is not required for pneumococcal transformation but together with XerS for
      resolution of chromosome dimers frequently formed in the process.
AB  - Homologous recombination (HR) is required for both genome maintenance and
      generation of diversity in eukaryotes and prokaryotes. This process initiates
      from single-stranded (ss) DNA and is driven by a universal recombinase, which
      promotes strand exchange between homologous sequences. The bacterial recombinase,
      RecA, is loaded onto ssDNA by recombinase loaders, RecBCD and RecFOR for genome
      maintenance. DprA was recently proposed as a third loader dedicated to genetic
      transformation. Here we assessed the role of RecFOR in transformation of the
      human pathogen Streptococcus pneumoniae. We firstly established that RecFOR
      proteins are not required for plasmid transformation, strongly suggesting that
      DprA ensures annealing of plasmid single-strands internalized in the process. We
      then observed no reduction in chromosomal transformation using a PCR fragment as
      donor, contrasting with the 10,000-fold drop in dprA- cells and demonstrating
      that RecFOR play no role in transformation. However, a ~1.45-fold drop in
      transformation was observed with total chromosomal DNA in recFOR mutants. To
      account for this limited deficit, we hypothesized that transformation with
      chromosomal DNA stimulated unexpectedly high frequency (>30% of cells) formation
      of chromosome dimers as an intermediate in the generation of tandem duplications,
      and that RecFOR were crucial for dimer resolution. We validated this hypothesis,
      showing that the site-specific recombinase XerS was also crucial for dimer
      resolution. An even higher frequency of dimer formation (>80% of cells) was
      promoted by interspecies transformation with Streptococcus mitis chromosomal DNA,
      which contains numerous inversions compared to pneumococcal chromosome, each
      potentially promoting dimerization. In the absence of RecFOR and XerS, dimers
      persist, as confirmed by DAPI staining, and can limit the efficiency of
      transformation, since resulting in loss of transformant chromosome. These
      findings strengthen the view that different HR machineries exist for genome
      maintenance and transformation in pneumococci. These observations presumably
      apply to most naturally transformable species. 

PMID- 25569616
TI  - Inviting the breach: confronting homophobia in the name of social justice.
AB  - In 2008 California was divided over Proposition 8, a measure designed to prohibit
      same-sex marriage. In this article, we focus on a university classroom setting to
      explore how discussions about Proposition 8 and homophobia led to what Turner
      (1986) termed a social drama. Drawing on student personal narratives as they
      moved through the stages of social drama, we provide a poignant example of the
      conflict that may erupt when homophobia and heteronormativity are part of the
      curriculum. After documenting the social drama, we offer pedagogical strategies
      and note the strategic ways Christian, hegemonic discourse is utilized during
      discussions about homophobia. 

PMID- 25569615
TI  - A computational framework for 3D mechanical modeling of plant morphogenesis with
      cellular resolution.
AB  - The link between genetic regulation and the definition of form and size during
      morphogenesis remains largely an open question in both plant and animal biology.
      This is partially due to the complexity of the process, involving extensive
      molecular networks, multiple feedbacks between different scales of organization
      and physical forces operating at multiple levels. Here we present a conceptual
      and modeling framework aimed at generating an integrated understanding of
      morphogenesis in plants. This framework is based on the biophysical properties of
      plant cells, which are under high internal turgor pressure, and are prevented
      from bursting because of the presence of a rigid cell wall. To control cell
      growth, the underlying molecular networks must interfere locally with the elastic
      and/or plastic extensibility of this cell wall. We present a model in the form of
      a three dimensional (3D) virtual tissue, where growth depends on the local
      modulation of wall mechanical properties and turgor pressure. The model shows how
      forces generated by turgor-pressure can act both cell autonomously and non-cell
      autonomously to drive growth in different directions. We use simulations to
      explore lateral organ formation at the shoot apical meristem. Although different
      scenarios lead to similar shape changes, they are not equivalent and lead to
      different, testable predictions regarding the mechanical and geometrical
      properties of the growing lateral organs. Using flower development as an example,
      we further show how a limited number of gene activities can explain the complex
      shape changes that accompany organ outgrowth. 

PMID- 25569618
TI  - Resistin-Like Molecule alpha in Allergen-Induced Pulmonary Vascular Remodeling.
AB  - Resistin-like molecule alpha (RELMalpha) has mitogenic, angiogenic,
      vasoconstrictive, and chemokine-like properties and is highly relevant in lung
      pathology. Here, we used RELMalpha knockout (Retnla(-/-)) mice to investigate the
      role of RELMalpha in pulmonary vascular remodeling after intermittent ovalbumin
      (OVA) challenge. We compared saline- and OVA-exposed wild-type (WT) mice and
      found that OVA induced significant increases in right ventricular systolic
      pressure, cardiac hypertrophy, pulmonary vascular remodeling of intra-alveolar
      arteries, goblet cell hyperplasia in airway epithelium, and intensive lung
      inflammation, especially perivascular inflammation. Genetic ablation of Retnla
      prevented the OVA-induced increase in pulmonary pressure and cardiac hypertrophy
      seen in WT mice. Histological analysis showed that Retnla(-/-) mice exhibited
      less vessel muscularization, less perivascular inflammation, reduced medial
      thickness of intra-alveolar vessels, and fewer goblet cells in upper airway
      epithelium (250-600 MUm) than did WT animals after OVA challenge. Gene expression
      profiles showed that genes associated with vascular remodeling, including those
      related to muscle protein, contractile fibers, and actin cytoskeleton, were
      expressed at a lower level in OVA-challenged Retnla(-/-) mice than in similarly
      treated WT mice. In addition, bronchoalveolar lavage from OVA-challenged Retnla(
      /-) mice had lower levels of cytokines, such as IL-1beta, -1 receptor antagonist,
      and -16, chemokine (C-X-C motif) ligand 1, -2, -9, -10, and -13, monocyte
      chemoattractant protein-1, macrophage colony-stimulating factor, TIMP
      metallopeptidase inhibitor-1, and triggering receptor expressed on myeloid cells
      1, than did that from WT mice when analyzed by cytokine array dot blots. Retnla
      knockout inhibited the OVA-induced T helper 17 response but not the T helper 2
      response. Altogether, our results suggest that RELMalpha is involved in immune
      response-induced pulmonary vascular remodeling and the associated increase in
      inflammation typically observed after OVA challenge. 

PMID- 25569621
TI  - Drug-Induced Acute Urinary Retention #287.

PMID- 25569619
TI  - The yeast La related protein Slf1p is a key activator of translation during the
      oxidative stress response.
AB  - The mechanisms by which RNA-binding proteins control the translation of subsets
      of mRNAs are not yet clear. Slf1p and Sro9p are atypical-La motif containing
      proteins which are members of a superfamily of RNA-binding proteins conserved in
      eukaryotes. RIP-Seq analysis of these two yeast proteins identified overlapping
      and distinct sets of mRNA targets, including highly translated mRNAs such as
      those encoding ribosomal proteins. In paralell, transcriptome analysis of
      slf1Delta and sro9Delta mutant strains indicated altered gene expression in
      similar functional classes of mRNAs following loss of each factor. The loss of
      SLF1 had a greater impact on the transcriptome, and in particular, revealed
      changes in genes involved in the oxidative stress response. slf1Delta cells are
      more sensitive to oxidants and RIP-Seq analysis of oxidatively stressed cells
      enriched Slf1p targets encoding antioxidants and other proteins required for
      oxidant tolerance. To quantify these effects at the protein level, we used label
      free mass spectrometry to compare the proteomes of wild-type and slf1Delta
      strains following oxidative stress. This analysis identified several proteins
      which are normally induced in response to hydrogen peroxide, but where this
      increase is attenuated in the slf1Delta mutant. Importantly, a significant number
      of the mRNAs encoding these targets were also identified as Slf1p-mRNA targets.
      We show that Slf1p remains associated with the few translating ribosomes
      following hydrogen peroxide stress and that Slf1p co-immunoprecipitates ribosomes
      and members of the eIF4E/eIF4G/Pab1p 'closed loop' complex suggesting that Slf1p
      interacts with actively translated mRNAs following stress. Finally, mutational
      analysis of SLF1 revealed a novel ribosome interacting domain in Slf1p,
      independent of its RNA binding La-motif. Together, our results indicate that
      Slf1p mediates a translational response to oxidative stress via mRNA-specific
      translational control. 

PMID- 25569620
TI  - Maturation of the HIV-1 core by a non-diffusional phase transition.
AB  - The formation of the HIV-1 core is the final step in the viral maturation
      pathway, resulting in the formation of infectious virus. Most current models for
      HIV-1 core formation suggest that, upon proteolytic cleavage from the immature
      Gag, capsid (CA) dissociates into the viral interior before reforming into the
      core. Here we present evidence for an alternate view of core formation by taking
      advantage of our serendipitous observation of large membrane-enclosed structures
      in HIV-1 supernatants from infected cells. Cryo-electron tomographic studies show
      that these structures, which contain ordered arrays of what is likely the
      membrane-associated matrix protein, contain multiple cores that can be captured
      at different stages of maturation. Our studies suggest that HIV maturation
      involves a non-diffusional phase transition in which the detaching layer of the
      cleaved CA lattice is gradually converted into a roll that ultimately forms the
      surface of the mature conical core. 

PMID- 25569622
TI  - Nutritional interventions in head and neck cancer patients undergoing
      chemoradiotherapy: a narrative review.
AB  - The present review aimed to define the role of nutritional interventions in the
      prevention and treatment of malnutrition in HNC patients undergoing CRT as well
      as their impact on CRT-related toxicity and survival. Head and neck cancer
      patients are frequently malnourished at the time of diagnosis and prior to the
      beginning of treatment. In addition, chemo-radiotherapy (CRT) causes or
      exacerbates symptoms, such as alteration or loss of taste, mucositis, xerostomia,
      fatigue, nausea and vomiting, with consequent worsening of malnutrition.
      Nutritional counseling (NC) and oral nutritional supplements (ONS) should be used
      to increase dietary intake and to prevent therapy-associated weight loss and
      interruption of radiation therapy. If obstructing cancer and/or mucositis
      interfere with swallowing, enteral nutrition should be delivered by tube.
      However, it seems that there is not sufficient evidence to determine the optimal
      method of enteral feeding. Prophylactic feeding through nasogastric tube or
      percutaneous gastrostomy to prevent weight loss, reduce dehydration and
      hospitalizations, and avoid treatment breaks has become relatively common.
      Compared to reactive feeding (patients are supported with oral nutritional
      supplements and when it is impossible to maintain nutritional requirements
      enteral feeding via a NGT or PEG is started), prophylactic feeding does not offer
      advantages in terms of nutritional outcomes, interruptions of radiotherapy and
      survival. Overall, it seems that further adequate prospective, randomized studies
      are needed to define the better nutritional intervention in head and neck cancer
      patients undergoing chemoradiotherapy. 

PMID- 25569623
TI  - Effects of black adzuki bean (Vigna angularis) extract on proliferation and
      differentiation of 3T3-L1 preadipocytes into mature adipocytes.
AB  - The aim of this work was to investigate the effects of black adzuki bean (BAB)
      extract on adipocytes, and to elucidate the cellular mechanisms. In order to
      examine the proliferation of preadipocytes and differentiating adipocytes, cell
      viability and DNA content were measured over a period of time. Lipid accumulation
      during cell differentiation and the molecular mechanisms underlying the effects
      of BAB on the transcriptional factors involved, with their anti-adipogenic
      effects, were also identified. We observed that BAB exhibits anti-adipogenic
      effects through the inhibition of proliferation, thereby lowering mRNA expression
      of C/EBPbeta and suppressing adipogenesis during the early stage of
      differentiation. This, in turn, resulted in a reduction of TG accumulation in a
      dose- and time-dependent manner. Treating the cells with BAB not only suppressed
      the adipogenesis-associated key transcription factors PPARgamma and C/EBPalpha
      but also significantly decreased the mRNA expression of GLUT4, FABP4, LPL and
      adiponectin. The expression of lipolytic genes like ATGL and HSL were higher in
      the treatment group than in the control. Overall, the black adzuki bean extract
      demonstrated an anti-adipogenic property, which makes it a potential dietary
      supplement for attenuation of obesity. 

PMID- 25569624
TI  - Milk consumption following exercise reduces subsequent energy intake in female
      recreational exercisers.
AB  - The aim of this study was to evaluate the effects of skimmed milk as a recovery
      drink following moderate-vigorous cycling exercise on subsequent appetite and
      energy intake in healthy, female recreational exercisers. Utilising a randomised
      cross-over design, nine female recreational exercisers (19.7 +/- 1.3 years)
      completed a VO2peak test followed by two main exercise trials. The main trials
      were conducted following a standardised breakfast. Following 30 min of moderate
      vigorous exercise (65% VO2peak), either 600 mL of skimmed milk or 600 mL of
      orange drink (475 mL orange juice from concentrate, 125 mL water), which were
      isoenergetic (0.88 MJ), were ingested, followed 60 min later with an ad libitum
      pasta meal. Absolute energy intake was reduced 25.2% +/- 16.6% after consuming
      milk compared to the orange drink (2.39 +/- 0.70 vs. 3.20 +/- 0.84 MJ,
      respectively; p = 0.001). Relative energy intake (in relation to the energy
      content of the recovery drinks and energy expenditure) was significantly lower
      after milk consumption compared to the orange drink (1.49 +/- 0.72 vs. 2.33 +/-
      0.90 MJ, respectively; p = 0.005). There were no differences in AUC (* 1 h)
      subjective appetite parameters (hunger, fullness and desire to eat) between
      trials. The consumption of skimmed milk following 30 min of moderate-vigorous
      cycling exercise reduces subsequent energy intake in female recreational
      exercisers.

PMID- 25569625
TI  - Curcumin inhibits gastric inflammation induced by Helicobacter pylori infection
      in a mouse model.
AB  - Helicobacter pylori (H. pylori) infection triggers a sequence of gastric
      alterations starting with an inflammation of the gastric mucosa that, in some
      cases, evolves to gastric cancer. Efficient vaccination has not been achieved,
      thus it is essential to find alternative therapies, particularly in the
      nutritional field. The current study evaluated whether curcumin could attenuate
      inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight
      C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected
      mice were used as controls. H. pylori infection in live mice was followed-up
      using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time
      polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed
      in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These
      mice showed an up-regulation of the expression of inflammatory cytokines and
      chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time
      points. Treatment with curcumin decreased the expression of all these mediators.
      No inflammation was observed by histology in this group. Curcumin treatment
      exerted a significant anti-inflammatory effect in H. pylori-infected mucosa,
      pointing to the promising role of a nutritional approach in the prevention of H.
      pylori induced deleterious inflammation while the eradication or prevention of
      colonization by effective vaccine is not available. 

PMID- 25569626
TI  - Molecular targets of naturopathy in cancer research: bridge to modern medicine.
AB  - The relevance of naturopathy (defined as the practice of medicine for the
      treatment of human diseases with natural agents) in human cancer is beginning to
      be appreciated, as documented by renewed interest in nutraceutical research, the
      natural anticancer agents of dietary origin. Because of their pleiotropic effects
      and the ability to modulate multiple signaling pathways, which is a good
      attribute of natural agents, nutraceuticals have frequently been demonstrated to
      re-sensitize drug-resistant cancers. The effectiveness of nutraceuticals can be
      further enhanced if the tools for the relative assessment of their molecular
      targets are readily available. Such information can be critical for determining
      their most effective uses. Here, we discuss the anticancer potential of
      nutraceuticals and the associated challenges that have interfered with their
      translational potential as a naturopathic approach for the management of cancers.
      In the years to come, an efficient screening and assessment of molecular targets
      will be the key to make rapid progress in the area of drug design and discovery,
      especially focusing on evidence-based development of naturopathy for the
      treatment of human malignancies. 

PMID- 25569627
TI  - Obesity promotes alterations in iron recycling.
AB  - Hepcidin is a key hormone that induces the degradation of ferroportin (FPN), a
      protein that exports iron from reticuloendothelial macrophages and enterocytes.
      The aim of the present study was to experimentally evaluate if the obesity
      induced by a high-fat diet (HFD) modifies the expression of FPN in macrophages
      and enterocytes, thus altering the iron bioavailability. In order to directly
      examine changes associated with iron metabolism in vivo, C57BL/6J mice were fed
      either a control or a HFD. Serum leptin levels were evaluated. The hepcidin,
      divalent metal transporter-1 (DMT1), FPN and ferritin genes were analyzed by real
      time polymerase chain reaction. The amount of iron present in both the liver and
      spleen was determined by flame atomic absorption spectrometry. Ferroportin
      localization within reticuloendothelial macrophages was observed by
      immunofluorescence microscopy. Obese animals were found to exhibit increased
      hepcidin gene expression, while iron accumulated in the spleen and liver. They
      also exhibited changes in the sublocation of splenic cellular FPN and a reduction
      in the FPN expression in the liver and the spleen, while no changes were observed
      in enterocytes. Possible explanations for the increased hepcidin expression
      observed in HFD animals may include: increased leptin levels, the liver iron
      accumulation or endoplasmic reticulum (ER) stress. Together, the results
      indicated that obesity promotes changes in iron bioavailability, since it altered
      the iron recycling function. 

PMID- 25569629
TI  - Purification of anti-bromelain antibodies by affinity precipitation using pNIPAm
      linked bromelain.
AB  - Affinity precipitation has emerged as a very useful technique for the
      purification of proteins. Here it has been employed for the purification of anti
      bromelain antibodies from rabbit serum. A system has been developed for
      reversibly binding and thermoprecipitating antibodies. Anti-bromelain antibodies
      were raised in rabbit by immunizing it with bromelain. Poly-N-isopropylacrylamide
      (pNIPAm)-bromelain conjugate was prepared and incubated with rabbit serum. After
      that the temperature was raised for thermal precipitation of the polymer.
      Antibodies were then eluted from the complex by incubating it with a small volume
      of buffer, pH 3.0. This method is very effective in concentrating the antibodies.
      Purity and specificity of the antibodies were checked by gel electrophoresis and
      enzyme-linked immunosorbent assay (ELISA), respectively. The study of the effect
      of pH and temperature on the binding of the antibodies to the conjugate showed
      that the optimum binding occurred at pH 8.0 and 25 degrees C.The polymer enzyme
      conjugate was further used for another cycle.

PMID- 25569628
TI  - Fast and accurate resonance assignment of small-to-large proteins by combining
      automated and manual approaches.
AB  - The process of resonance assignment is fundamental to most NMR studies of protein
      structure and dynamics. Unfortunately, the manual assignment of residues is
      tedious and time-consuming, and can represent a significant bottleneck for
      further characterization. Furthermore, while automated approaches have been
      developed, they are often limited in their accuracy, particularly for larger
      proteins. Here, we address this by introducing the software COMPASS, which, by
      combining automated resonance assignment with manual intervention, is able to
      achieve accuracy approaching that from manual assignments at greatly accelerated
      speeds. Moreover, by including the option to compensate for isotope shift effects
      in deuterated proteins, COMPASS is far more accurate for larger proteins than
      existing automated methods. COMPASS is an open-source project licensed under GNU
      General Public License and is available for download from
      http://www.liu.se/forskning/foass/tidigare-foass/patrik-lundstrom/software?l=en.
      Source code and binaries for Linux, Mac OS X and Microsoft Windows are available.

PMID- 25569632
TI  - Working miracles for the NHS.

PMID- 25569630
TI  - Type 3 secretion system cluster 3 is a critical virulence determinant for lung
      specific melioidosis.
AB  - Burkholderia pseudomallei, the bacterial agent of melioidosis, causes disease
      through inhalation of infectious particles, and is classified as a Tier 1 Select
      Agent. Optical diagnostic imaging has demonstrated that murine respiratory
      disease models are subject to significant upper respiratory tract (URT)
      colonization. Because human melioidosis is not associated with URT colonization
      as a prominent presentation, we hypothesized that lung-specific delivery of B.
      pseudomallei may enhance our ability to study respiratory melioidosis in mice. We
      compared intranasal and intubation-mediated intratracheal (IMIT) instillation of
      bacteria and found that the absence of URT colonization correlates with an
      increased bacterial pneumonia and systemic disease progression. Comparison of the
      LD50 of luminescent B. pseudomallei strain, JW280, in intranasal and IMIT
      challenges of albino C57BL/6J mice identified a significant decrease in the LD50
      using IMIT. We subsequently examined the LD50 of both capsular polysaccharide and
      Type 3 Secretion System cluster 3 (T3SS3) mutants by IMIT challenge of mice and
      found that the capsule mutant was attenuated 6.8 fold, while the T3SS3 mutant was
      attenuated 290 fold, demonstrating that T3SS3 is critical to respiratory
      melioidosis. Our previously reported intranasal challenge studies, which involve
      significant URT colonization, did not identify a dissemination defect for capsule
      mutants; however, we now report that capsule mutants exhibit significantly
      reduced dissemination from the lung following lung-specific instillation,
      suggesting that capsule mutants are competent to spread from the URT, but not the
      lung. We also report that a T3SS3 mutant is defective for dissemination following
      lung-specific delivery, and also exhibits in vivo growth defects in the lung.
      These findings highlight the T3SS3 as a critical virulence system for respiratory
      melioidosis, not only in the lung, but also for subsequent spread beyond the lung
      using a model system uniquely capable to characterize the fate of lung-delivered
      pathogen. 

PMID- 25569631
TI  - Multi-synergetic ZnO platform for high performance cancer therapy.
AB  - ZnO platforms were evaluated for designing a high-performance anticancer drug
      (daunorubicin) carrier. Hollow structured ZnO, compared with nanorods, acts as a
      multi-purpose entity by serving as smart carriers and exhibiting synergetic
      photodynamic cytotoxic effects, which are ascribed to their high-specific surface
      area, hollow interior, pH-responsiveness and inherent photodynamism. 

PMID- 25569633
TI  - Substrate-induced phase of a [1]benzothieno[3,2-b]benzothiophene derivative and
      phase evolution by aging and solvent vapor annealing.
AB  - Substrate-induced phases (SIPs) are polymorphic phases that are found in thin
      films of a material and are different from the single crystal or "bulk" structure
      of a material. In this work, we investigate the presence of a SIP in the family
      of [1]benzothieno[3,2-b]benzothiophene (BTBT) organic semiconductors and the
      effect of aging and solvent vapor annealing on the film structure. Through
      extensive X-ray structural investigations of spin coated films, we find a SIP
      with a significantly different structure to that found in single crystals of the
      same material forms; the SIP has a herringbone motif while single crystals
      display layered pi-pi stacking. Over time, the structure of the film is found to
      slowly convert to the single crystal structure. Solvent vapor annealing initiates
      the same structural evolution process but at a greatly increased rate, and near
      complete conversion can be achieved in a short period of time. As properties such
      as charge transport capability are determined by the molecular structure, this
      work highlights the importance of understanding and controlling the structure of
      organic semiconductor films and presents a simple method to control the film
      structure by solvent vapor annealing. 

PMID- 25569635
TI  - Eosinophil-Specific Granules in Tumor Cell Cytoplasm: Unusual Ultrastructural
      Findings in a Case of Diffuse-Type Gastric Carcinoma.
AB  - A case of desmoplastic variant of diffuse-type gastric carcinoma in a 72-year-old
      woman is reported. Microscopic findings included poorly cohesive tumor cells,
      resembling mononuclear inflammatory cells, prominent diffuse desmoplasia, and
      tumor-associated tissue eosinophilia. Electron microscopy confirmed the
      undifferentiated phenotype of tumor cells and disclosed activated eosinophils in
      the tumor stroma. Eosinophil-specific granules were found either free in the
      tumor stroma or within the cytoplasm of some tumor cells. Electron microscopy
      provided also circumstantial evidence of phagocytosis of apoptotic eosinophils by
      tumor cells. Extracellular, membrane-bound, eosinophil-specific granules have
      been long recognized in tissues associated with eosinophilia, including allergic
      diseases, inflammatory responses to helminths, and in stroma of some neoplasms.
      Our ultrastructural study now extends these findings and provides additional
      morphological evidence of eosinophil-specific granules within the cytoplasm of
      gastric carcinoma cells. 

PMID- 25569634
TI  - Feasibility and effectiveness of an asthma/COPD service for primary care: a cross
      sectional baseline description and longitudinal results.
AB  - BACKGROUND: In 2007, an Asthma/chronic obstructive pulmonary disease (COPD) (AC)
      service was implemented in the North of the Netherlands to support General
      Practitioners (GPs) by providing advice from pulmonologists on a systematic
      basis. AIMS: To evaluate the feasibility and effectiveness of this service on
      patient-related outcomes. METHODS: We report baseline data on 11,401 patients and
      follow-up data from 2,556 patients. GPs can refer all patients with possible
      obstructive airway disease (OAD) to the service, which is conducted by the local
      laboratory. Patients are assessed in the laboratory using questionnaires and
      spirometry. Pulmonologists inspect the data through the internet and send the GP
      diagnosis and management advice. RESULTS: A total of 11,401 patients were
      assessed by the service, covering almost 60% of all adult patients with projected
      asthma or COPD in the area. In all, 46% (n = 5,268) of the patients were
      diagnosed with asthma, 18% (n = 2,019) with COPD and 7% (n = 788) with the
      overlap syndrome. A total of 740 (7%) patients were followed up after 3 months
      because the GP advised them to change medication. In this group, the proportion
      of unstable COPD patients (Clinical COPD Questionnaire (CCQ) ? 1) decreased from
      63% (n = 92) at baseline to 49% (n = 72). The proportion of patients with
      uncontrolled asthma (Asthma Control Questionnaire (ACQ) ? 1.5) decreased from 41%
      (n = 204) to 23% (n = 115). In all, 938 (8%) patients were followed up after 12
      months. From these patients, the proportion of unstable COPD patients (CCQ ? 1)
      decreased from 47% (n = 115) to 44% (n = 107). The proportion of patients with
      uncontrolled asthma (ACQ?1.5) decreased from 16% (n = 95) to 14% (n = 85).
      CONCLUSION: The AC service assessed a considerable proportion of patients with
      OAD in the area, improved patients' outcomes, and is considered to be feasible
      and effective.

PMID- 25569636
TI  - In Memoriam: Joseph Ka Hoi Wong, MD, FRCSC (1954-2014).

PMID- 25569638
TI  - Differential MIR-21 expression in plasma from mesenteric versus peripheral veins:
      an observational study of disease-free survival in surgically resected colon
      cancer patients.
AB  - Findings on the role of plasma miR-21 expression in colorectal cancer are
      contradictory. Before reaching a peripheral vein (PV), microRNAs released by the
      tumor are dispersed throughout the body. We hypothesized that blood drawn from
      the mesenteric vein (MV) near the site of the primary tumor could provide more
      homogeneous information than blood drawn from the PV.We have analyzed miR-21
      expression in matched samples of tumor tissue, normal tissue, MV plasma, and PV
      plasma in 57 surgically resected patients with colon cancer and correlated our
      findings with clinical characteristics and disease-free survival (DFS).miR-21
      expression was higher in MV than PV plasma (P = 0.014) and in tumor than in
      normal tissue (P < 0.001). Patients with high levels of miR-21 in MV plasma had
      shorter DFS (P = 0.05) than those with low levels, and those with high levels in
      both MV and PV plasma had shorter DFS than all other patients (P = 0.01).Our
      findings suggest that the primary tumor in colon cancer releases high
      concentrations of miR-21 in the MV but that these concentrations are later
      diluted in the circulatory system. MV expression of miR-21 may be a stronger
      prognostic marker than PV expression. 

PMID- 25569637
TI  - Metastatic tumors of the penis: a report of 8 cases and review of the literature.
AB  - The purpose of this study was to report the clinical characteristics, treatments,
      and outcomes of secondary penile cancers and review the literature of this rare
      condition.The records of 8 patients with metastatic penile cancer treated at our
      hospital from 2006 to 2013 were analyzed. A search of medical databases was
      conducted.Patient symptoms included penile mass (n = 7, 5 had concomitant pain)
      and acute urine retention (n = 1). The primary cancers included bladder, lung,
      gastric, liver, and prostate malignancies and 1 case of pulmonary epithelioid
      hemangioendothelioma. The longest time from diagnosis of the primary cancer to
      metastatic penile cancer was 16 years and the shortest was 7 months. Six patients
      were treated with phallectomy, 1 with resection of the mass, and 1 with only a
      biopsy because of advanced metastatic disease. Five patients are deceased at the
      time of this report, and the longest and shortest survival times (from the
      diagnosis of primary cancer to the death) were 16 years and 9 months,
      respectively. The literature review identified 17 cases reported since 2011,
      bringing the total number of reported cases to 480. Genitourinary cancer,
      primarily bladder and prostate, account for approximately 70 of the primary
      cancer sites and gastrointestinal cancers account for approximately 21%.
      Approximately half of the patients had died of their disease within 1 year of the
      diagnosis of penile metastasis.The prognosis of metastatic penile cancer is poor.
      Most primary cancers are in the urologic or gastrointestinal systems. Surgery and
      adjunctive therapy may improve symptoms, but fail to prolong survival. 

PMID- 25569639
TI  - Recursive partitioning analysis of lymph node ratio in breast cancer patients.
AB  - Lymph node ratio (LNR) is a powerful prognostic factor for breast cancer. We
      conducted a recursive partitioning analysis (RPA) of the LNR to identify the
      prognostic risk groups in breast cancer patients. Records of newly diagnosed
      breast cancer patients between 2002 and 2006 were searched in the Taiwan Cancer
      Database. The end of follow-up was December 31, 2009. We excluded patients with
      distant metastases, inflammatory breast cancer, survival <1 month, no mastectomy,
      or missing lymph node status. Primary outcome was 5-year overall survival (OS).
      For univariate significant predictors, RPA were used to determine the risk
      groups. Among the 11,349 eligible patients, we identified 4 prognostic factors
      (including LNR) for survival, resulting in 8 terminal nodes. The LNR cutoffs were
      0.038, 0.259, and 0.738, which divided LNR into 4 categories: very low (LNR <=
      0.038), low (0.038 < LNR <= 0.259), moderate (0.259 < LNR <= 0.738), and high
      (0.738 < LNR). Then, 4 risk groups were determined as follows: Class 1 (very low
      risk, 8,265 patients), Class 2 (low risk, 1,901 patients), Class 3 (moderate
      risk, 274 patients), and Class 4 (high risk, 900 patients). The 5-year OS for
      Class 1, 2, 3, and 4 were 93.2%, 83.1%, 72.3%, and 56.9%, respectively (P<
      0.001). The hazard ratio of death was 2.70, 4.52, and 8.59 (95% confidence
      interval 2.32-3.13, 3.49-5.86, and 7.48-9.88, respectively) times for Class 2, 3,
      and 4 compared with Class 1 (P < 0.001). In conclusion, we identified the optimal
      cutoff LNR values based on RPA and determined the related risk groups, which
      successfully predict 5-year OS in breast cancer patients. 

PMID- 25569642
TI  - Relationship between developmental dislocation of the hip in infant and
      acetabular dysplasia at skeletal maturity.
AB  - Previous reports demonstrated 8-60% patients treated for developmental
      dislocation of hip (DDH) in infancy have residual acetabular dysplasia (AD) at
      skeletal maturity. AD patients reportedly exhibit abnormal morphology of the
      pelvis, high rates of comorbid spinal congenital anomalies and high bone mineral
      density. These physical findings suggest that AD patients have genetic
      background. We examined the percentage of AD patients with hip pain at skeletal
      maturity having a history of DDH in infancy and the correlation between the
      severity of AD at skeletal maturity and history of DDH treatment to investigate
      the relationship between AD and DDH.A total of 245 patients were radiographically
      examined for any history of DDH treatment in infancy. The study included 226
      women and 19 men with a mean age at examination of 40.7 years (range 17-59
      years).Eighty-eight patients (36%) had a history of DDH treatment (DDH group) and
      the remaining 157 patients (64%) had no history of DDH treatment (non-DDH group).
      The average age was lower and acetabular angle was larger in the DDH group. There
      was a significant increasing trend of the percentage of DDH patients associated
      with the severity of AD classified with CE, acetabular angle, and acetabular roof
      angle.Our data suggest that there are several AD patients without a history of
      DDH in Japan, and AD in patients without a history of DDH has different
      characteristics from AD in patients with a history of DDH. 

PMID- 25569641
TI  - Comprehensive description of clinical characteristics of a large systemic lupus
      erythematosus cohort from the Spanish Rheumatology Society Lupus Registry
      (RELESSER) with emphasis on complete versus incomplete lupus differences.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
      multiple organ involvement and pronounced racial and ethnic heterogeneity. The
      aims of the present work were (1) to describe the cumulative clinical
      characteristics of those patients included in the Spanish Rheumatology Society
      SLE Registry (RELESSER), focusing on the differences between patients who
      fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria
      (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient
      characteristics with those documented in other multicentric SLE
      registries.RELESSER is a multicenter hospital-based registry, with a collection
      of data from a large, representative sample of adult patients with SLE (1997 ACR
      criteria) seen at Spanish rheumatology departments. The registry includes
      demographic data, comprehensive descriptions of clinical manifestations, as well
      as information about disease activity and severity, cumulative damage,
      comorbidities, treatments and mortality, using variables with highly standardized
      definitions.A total of 4.024 SLE patients (91% with >=4 ACR criteria) were
      included. Ninety percent were women with a mean age at diagnosis of 35.4 years
      and a median duration of disease of 11.0 years. As expected, most SLE
      manifestations were more frequent in SLE patients than in iSLE ones and every one
      of the ACR criteria was also associated with SLE condition; this was particularly
      true of malar rash, oral ulcers and renal disorder. The analysis-adjusted by
      gender, age at diagnosis, and disease duration-revealed that higher disease
      activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95%
      CI: 1.08-1.20 (P < 0.001); 1.29; 95% CI: 1.15-1.44 (P < 0.001); and 2.10; 95% CI:
      1.83-2.42 (P < 0.001), respectively]. These results support the hypothesis that
      iSLE behaves as a relative stable and mild disease. SLE patients from the
      RELESSER register do not appear to differ substantially from other Caucasian
      populations and although activity [median SELENA-SLEDA: 2 (IQ: 0-4)], damage
      [median SLICC/ACR/DI: 1 (IQ: 0-2)], and severity [median KATZ index: 2 (IQ: 1-3)]
      scores were low, 1 of every 4 deaths was due to SLE activity.RELESSER represents
      the largest European SLE registry established to date, providing comprehensive,
      reliable and updated information on SLE in the southern European population. 

PMID- 25569640
TI  - Bisphenol A and hormone-associated cancers: current progress and perspectives.
AB  - Bisphenol A (BPA), a carbon-based synthetic compound, exhibits hormone-like
      properties and is present ubiquitously in the environment and in human tissues
      due to its widespread use and biological accumulation. BPA can mimic estrogen to
      interact with estrogen receptors alpha and beta, leading to changes in cell
      proliferation, apoptosis, or migration and thereby, contributing to cancer
      development and progression. At the genetic level, BPA has been shown to be
      involved in multiple oncogenic signaling pathways, such as the STAT3, MAPK, and
      PI3K/AKT pathways. Moreover, BPA may also interact with other steroid receptors
      (such as androgen receptor) and plays a role in prostate cancer development. This
      review summarizes the current literature regarding human exposure to BPA, the
      endocrine-disrupting effects of BPA, and the role of BPA in hormone-associated
      cancers of the breast, ovary, and prostate. 

PMID- 25569643
TI  - Biomechanical evaluation of interfragmentary compression at tibia plateau
      fractures in vitro using different fixation techniques: a CONSORT-compliant
      article.
AB  - Reliable osteosynthesis of intraarticular fractures depends on lasting
      interfragmentary compression. Its amount differs in the applied fixation method.
      The interfragmentary compression of cancellous and cortical lag screws and angle
      stable locking plates was quantified in an osteoporotic and non-osteoporotic
      synthetic human bone model.A split fracture of the lateral tibia plateau (AO/OTA
      type 41-B1.1) was mimicked by an osteotomy in right adult synthetic human tibiae
      with hard or soft cancellous bone. Specimens were fixed with either two 6.5 mm
      cancellous, four 3.5 mm cortical lag screws, or 3.5 mm LCP proximal lateral tibia
      plate preliminary compresed by a reduction clamp (n = 5 per group). A pressure
      sensor film was used to register the interfragmentary compression. One-way
      analysis of variance (ANOVA) with Bonferroni post hoc correction was performed
      for statistical analysis (p < 0.05).Interfragmentary compression under reduction
      clamp was 0.59 +/- 0.12 MPa in the non-osteoporotic and 0.55 +/- 0.14 MPa in the
      osteoporotic group. The locking plate itself maintained the compression in non
      osteoporotic (0.53 +/- 0.11 MPa) and osteoporotic bone (0.50 +/- 0.14 MPa). Four
      3.5 mm cortical lag screws provided a compression of 1.69 +/- 0.65 MPa in non
      osteoporotic bone, being not significantly different to the osteoporotic bone
      group (1.43 +/- 0.47 MPa, P = 1.0). Two 6.5 mm cancellous lag screws showed a
      significantly higher compression in non-osteoporotic (2.1 +/- 0.59 MPa) compared
      to osteoporotic (0.77 +/- 0.21 MPa, P < 0.01) bone.Angle stable locking plates
      maintained the compression preliminarily applied by a reduction clamp. Two 6.5 mm
      cancellous lag screws are especially suited for non-osteoporotic bone, whereas
      four 3.5 mm cortical screws exhibited comparable compression in both bone
      qualities. 

PMID- 25569644
TI  - Association between the XRCC6 polymorphisms and cancer risks: a systematic review
      and meta-analysis.
AB  - A number of studies have been carried out to investigate the association of X-ray
      repair complementing defective repair in Chinese hamster cells 6 (XRCC6)
      polymorphisms and cancer risks, and the results remained inconsistent and
      inconclusive.To assess the effect of XRCC6 polymorphisms on cancer
      susceptibility, we conducted a meta-analysis, up to May 23rd 2014, 6267 cases
      with different types of tumor and 7536 controls from 20 published case-control
      studies. Summary odds ratios and corresponding 95% confidence intervals for XRCC6
      polymorphism and cancer risk were estimated using fixed- or random-effects models
      when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic
      test, and the sources of heterogeneity were explored by subgroup analyses,
      logistic meta-regression analyses and Galbraith plot. Publication bias was
      evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also
      performed.The rs2267437 polymorphism was associated with a significant increase
      in risks of overall cancers, breast cancer, renal cell carcinoma and
      hepatocellular carcinoma, and it could increase the cancer risk in Asian
      population; the rs5751129 polymorphism could increase the cancer risk in overall
      cancers; the rs132770 polymorphism was associated with the increased renal cell
      carcinoma risk; furthermore, the rs132793 polymorphism could decrease breast
      cancer risk and increase risks in "other cancers".Overall, the results provided
      evidences that the single nucleotide polymorphisms in XRCC6 promoter region might
      play different roles in various cancers, indicating different cancers have
      different tumorigenesis mechanisms. Our studies may perhaps supplement for the
      disease monitoring of cancers in the future, and additional studies to determine
      the exact molecular mechanism might provide us with interventions to protect the
      susceptible subgroups. 

PMID- 25569645
TI  - Markers of cardiac dysfunction in cognitive impairment and dementia.
AB  - Markers of cardiac dysfunction such as amino terminal pro-brain natriuretic
      peptide (NTpro-BNP) and high sensitivity cardiac troponin T (hs-cTnT) may be
      associated with dementia. However, limited data exist on their association with
      either pre-dementia stages, that is, cognitive impairment no dementia (CIND), or
      the burden of cerebrovascular diseases (CeVD).We therefore, examined the
      association of these biomarkers of cardiac dysfunction with CeVD in both CIND and
      dementia.A case-control study, with cases recruited from memory clinics and
      controls from memory clinics and community. All subjects underwent collection of
      blood samples, neuropsychological assessment, and neuroimaging. Subjects were
      classified as CIND and dementia based on clinical criteria whilst significant
      CeVD was defined as the presence of cortical infarcts and/or more than 2 lacunes
      and/or confluent white matter lesions in two regions of brain on Age-Related
      White Matter Changes Scale.We included a total of 35 controls (mean age: 65.9
      years), 78 CIND (mean age: 70.2 years) and 80 cases with dementia (mean age: 75.6
      years). Plasma concentrations of hs-cTnT were associated significantly with CeVD
      in both CIND (odds ratios [OR]: 9.05; 95% confidence interval [CI]: 1.64-49.79)
      and dementia (OR: 16.89; 95%CI: 2.02-142.67). In addition, NTpro-BNP was
      associated with dementia with CeVD (OR: 7.74; 95%CI: 1.23-48.58). These
      associations were independent of other vascular risk factors.In this study, we
      showed that plasma NTproBNP and hs-cTnT are associated with dementia and CIND,
      only when accompanied by presence of CeVD. 

PMID- 25569646
TI  - Emergency department visits related to cirrhosis: a retrospective study of the
      nationwide emergency department sample 2006 to 2011.
AB  - There is scant literature about cirrhosis and its associated complications in a
      non-hospitalized population.To study the epidemiology of cirrhosis-associated
      Emergency Department visits in the US.Estimates were calculated in patients' >=18
      years using the Nationwide Emergency Department Sample.The number of visits
      associated with an International Classification of Diseases-9 diagnosis code of
      cirrhosis increased non-significantly from 23.81/10,000 population (2006) to
      23.9/10,000 population (2011; P = 0.05). A majority of these patients (75.30%)
      underwent hospital admission, the greatest risk factor for this was the presence
      of >=3 comorbidities (adjusted odds ratio 30.8; 95% Confidence Interval 30.4
      31.2). Infection was the most frequent concurrent complicating diagnosis
      associated with cirrhosis (20.1%). There was a decreased incidence in most of the
      complicating conditions except for hepatorenal syndrome and spontaneous bacterial
      peritonitis.Our results indicate a stable trend for cirrhosis-associated
      Emergency Department visits from 2006 to 2011. Further studies are required to
      investigate the increased incidence of spontaneous bacterial peritonitis and
      hepatorenal renal syndrome in the cirrhotic population. 

PMID- 25569647
TI  - A new real-time method for detecting the effect of fentanyl using the
      preoperative pressure pain threshold and Narcotrend index: a randomized study in
      female surgery patients.
AB  - Individual variability in the effects of opioid analgesics such as fentanyl
      remains a major challenge for tailored pharmacological treatment including
      postoperative analgesia. This study aimed to establish a new real-time method for
      detecting the effects of fentanyl and their individual differences in the
      preoperative period, using the pressure pain threshold (PPT) and Narcotrend index
      (NTI) test.Eighty women undergoing elective surgery under general anesthesia were
      enrolled in this randomized, double-blinded, placebo-controlled study to receive
      either intravenous fentanyl (Group F) or saline (Group S). Before (T1) and 5 (T2)
      and 10 min (T3) after intravenous injection, the PPT, NTI, respiratory rate,
      heart rate, blood pressure, and pulse oxygen saturation were measured. The
      initial time at which the Narcotrend index showed a decline was also recorded.In
      total, 40 patients in Group S and 38 patients in Group F were included in the
      final analysis. At 5 min and 10 min after intravenous fentanyl administration,
      the analgesic effect was determined by measuring the PPT, which was significantly
      increased (P < 0.001), and the sedative effect was detected using the NTI, which
      was significantly decreased (P < 0.001). The distribution of percentage changes
      of the PPT and NTI showed individual differences. At T2 and T3, the absolute
      changes in NTI and PPT were positively correlated (r = 0.444 at T2, P = 0.005; r
      = 0.332 at T3, P = 0.042).Through the PPT and NTI, it was feasible to easily
      detect the effects of fentanyl and their individual differences in real time
      before induction of anesthesia in the operation room. This method could
      potentially be applied to preoperatively determine patients' sensitivity to
      fentanyl. 

PMID- 25569648
TI  - Cord blood PRF1 methylation patterns and risk of lower respiratory tract
      infections in infants: findings from the Ulm Birth Cohort.
AB  - Lower respiratory tract infections (LRTIs) are a major cause of morbidity in
      children. DNA methylation provides a mechanism for transmitting environmental
      effects on the genome, but its potential role in LRTIs is not well studied. We
      investigated the methylation pattern of an enhancer region of the immune effector
      gene perforin-1 (PRF1), which encodes a cytolytic molecule of cytotoxic T
      lymphocytes (CTLs) and natural killer cells (NK), in cord blood DNA of children
      recruited in a German birth cohort in association with LRTIs in the first year of
      life.Pyrosequencing was used to determine the methylation levels of target
      cytosine-phosphate-guanines (CpGs) in a 2-stage case-control design. Cases were
      identified as children who developed >=2 episodes of physician-recorded LRTIs
      during the first year of life and controls as children who had none. Discovery (n
      = 87) and replication (n = 90) sets were arranged in trios of 1 case and 2
      controls matched for sex and season of birth.Logistic regression analysis
      revealed higher levels of methylation at a CpG that corresponds to a signal
      transducer and activator of transcription 5 (STAT5) responsive enhancer in the
      discovery (odds ratio [OR] per 1% methylation difference 1.24, 95% confidence
      interval [CI] 1.03-1.50) and replication (OR per 1% methylation difference 1.25,
      95% CI 1.04-1.50) sets. Adjustment for having siblings <5 years old in the
      discovery and replication sets produced ORs of 1.19 (95% CI 0.98-1.45) and 1.25
      (95% CI 1.04-1.50), respectively. Adjustment for gestational age in the
      replication set had no influence on the results. Methylation levels at adjacent
      CpGs varied with maternal age, smoking, education, and having siblings <5 years
      old.Our data support an association between cord blood PRF1 enhancer methylation
      patterns and subsequent risk of LRTIs in infants. Methylation levels at specific
      CpGs of the PRF1 enhancer varied according to maternal and family environmental
      factors suggesting a role for DNA methylation in mediating environmental
      influences on gene function. 

PMID- 25569649
TI  - Laparoscopic peritoneal lavage: a definitive treatment for diverticular
      peritonitis or a "bridge" to elective laparoscopic sigmoidectomy?: a systematic
      review.
AB  - To this day, the treatment of generalized peritonitis secondary to diverticular
      perforation is still controversial. Recently, in patients with acute sigmoid
      diverticulitis, laparoscopic lavage and drainage has gained a wide interest as an
      alternative to resection. Based on this backdrop, we decided to perform a
      systematic review of the literature to evaluate the safety, feasibility, and
      efficacy of peritoneal lavage in perforated diverticular disease.A bibliographic
      search was performed in PubMed for case series and comparative studies published
      between January 1992 and February 2014 describing laparoscopic peritoneal lavage
      in patients with perforated diverticulitis.A total of 19 articles consisting of
      10 cohort studies, 8 case series, and 1 controlled clinical trial met the
      inclusion criteria and were reviewed. In total these studies analyzed data from
      871 patients. The mean follow-up time ranged from 1.5 to 96 months when reported.
      In 11 studies, the success rate of laparoscopic peritoneal lavage, defined as
      patients alive without surgical treatment for a recurrent episode of
      diverticulitis, was 24.3%. In patients with Hinchey stage III diverticulitis, the
      incidence of laparotomy conversion was 1%, whereas in patients with stage IV it
      was 45%. The 30-day postoperative mortality rate was 2.9%. The 30-day
      postoperative reintervention rate was 4.9%, whereas 2% of patients required a
      percutaneous drainage. Readmission rate after the first hospitalization for
      recurrent diverticulitis was 6%. Most patients who were readmitted (69%) required
      redo surgery. A 2-stage laparoscopic intervention was performed in 18.3% of
      patients.Laparoscopic peritoneal lavage should be considered an effective and
      safe option for the treatment of patients with sigmoid diverticulitis with
      Hinchey stage III peritonitis; it can also be consider as a "bridge" surgical
      step combined with a delayed and elective laparoscopic sigmoidectomy in order to
      avoid a Hartmann procedure. This minimally invasive staged approach should be
      considered for patients without systemic toxicity and in centers experienced in
      minimally invasive surgery techniques. Further evidence is needed, and the
      ongoing RCTs will better define the role of the laparoscopic peritoneal
      lavage/drainage in the treatment of patients with complicated diverticulitis. 

PMID- 25569650
TI  - A cross-sectional observational study of pneumococcal carriage in children, their
      parents, and older adults following the introduction of the 7-valent pneumococcal
      conjugate vaccine.
AB  - Using nasopharyngeal carriage as a marker of vaccine impact, pneumococcal
      colonization and its relation to invasive disease were examined in children,
      their parents, and older adults in the United Kingdom following introduction of 7
      valent pneumococcal conjugate vaccine (PCV7) and prior to 13-valent pneumococcal
      conjugate vaccine (PCV13).A cross-sectional observational study was conducted,
      collecting nasopharyngeal swabs from children aged 25 to 55 months who had
      previously received 3 doses of PCV7, their parents, and adults aged >=65 years.
      Pneumococcal serotyping was conducted according to World Health Organization
      guidelines with nontypeable isolates further analyzed by molecular serotyping. A
      national invasive disease surveillance program was conducted throughout the
      corresponding period.Pneumococcus was isolated from 47% of children, 9% of
      parents, and 2.2% of older adults. For these groups, the percentage of serotypes
      covered by PCV7 were 1.5%, 0.0%, and 15.4%, with a further 20.1%, 44.4%, and 7.7%
      coverage added by those in PCV13. In each group, the percentage of disease due to
      serotypes covered by PCV7 were 1.0%, 7.4% and 5.1% with a further 65.3%, 42.1%,
      and 61.4% attributed to those in PCV13.The prevalence of carriage is the highest
      in children, with direct vaccine impact exemplified by low carriage and disease
      prevalence of PCV7 serotypes in vaccinated children, whereas the indirect effects
      of herd protection are implied by similar observations in unvaccinated parents
      and older adults. 

PMID- 25569651
TI  - Increased risk of deep vein thrombosis and pulmonary thromboembolism in patients
      with organophosphate intoxication: a nationwide prospective cohort study.
AB  - Organophosphate (OP) poisoning is a critical cause of morbidity and mortality
      worldwide. We conducted a nationwide longitudinal cohort study to investigate the
      development of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE)
      among patients admitted with OP intoxication.We identified patients with OP
      intoxication by using the Taiwan National Health Insurance Research Database and
      enrolled 9223 patients who were hospitalized for OP intoxication between 2000 and
      2011. OP intoxication was diagnosed based on a clinical assessment and serum
      acetylcholinesterase levels at the time of hospital admission. Each patient in
      the OP intoxication cohort was randomly frequency matched with 4 patients without
      OP intoxication based on their age, sex, and index year (36,892 patients as
      control cohort), and all patients were observed from the index date until the
      appearance of a DVT or a PTE event, or until December 31, 2011. We analyzed the
      risks of DVT and PTE by using Cox proportional hazards regression models that
      included the demographic variables of sex, age, and comorbidities (eg,
      hypertension, diabetes, cerebral vascular disease, heart failure, all cancer
      types, and lower leg fracture or surgery).The results revealed a significantly
      increased risk of developing DVT among patients with OP poisoning (adjusted
      hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.03-2.34) but not PTE
      (adjusted HR = 1.44; 95% CI = 0.83-2.52). Among the patients without
      comorbidities, the OP poisoning patients compared with controls had a higher
      adjusted HR of 2.12 (95% CI = 1.21-3.71) for DVT.The results of this nationwide
      cohort study indicate that the risk of developing DVT is markedly higher in
      patients with OP intoxication compared with that of the general population. 

PMID- 25569652
TI  - Qigong for hypertension: a systematic review.
AB  - The purpose of this review was to evaluate the efficacy and safety of qigong for
      hypertension.A systematic literature search was performed in 7 databases from
      their respective inceptions until April 2014, including the Cochrane Library,
      EMBASE, PubMed, Chinese Scientific Journal Database, Chinese Biomedical
      Literature Database, Wanfang database, and Chinese National Knowledge
      Infrastructure. Randomized controlled trials of qigong as either monotherapy or
      adjunctive therapy with antihypertensive drugs versus no intervention, exercise,
      or antihypertensive drugs for hypertension were identified. The risk of bias was
      assessed using the tool described in Cochrane Handbook for Systematic Review of
      Interventions, version 5.1.0.Twenty trials containing 2349 hypertensive patients
      were included in the meta-analysis. The risk of bias was generally high. Compared
      with no intervention, qigong significantly reduced systolic blood pressure (SBP)
      (weighted mean difference [WMD] = -17.40 mm Hg, 95% confidence interval [CI] 
      21.06 to -13.74, P < 0.00001) and diastolic blood pressure (DBP) (WMD = -10.15 mm
      Hg, 95% CI -13.99 to -6.30, P < 0.00001). Qigong was inferior to exercise in
      decreasing SBP (WMD = 6.51 mm Hg, 95% CI 2.81 to 10.21, P = 0.0006), but no
      significant difference between the effects of qigong and exercise on DBP (WMD =
      0.67 mm Hg, 95% CI -1.39 to 2.73, P = 0.52) was identified. Compared with
      antihypertensive drugs, qigong produced a clinically meaningful but not
      statistically significant reduction in SBP (WMD = -7.91 mm Hg, 95% CI -16.81 to
      1.00, P = 0.08), but appeared to be more effective in lowering DBP (WMD = -6.08
      mm Hg, 95% CI -9.58 to -2.58, P = 0.0007). Qigong plus antihypertensive drugs
      significantly lowered both SBP (WMD = -11.99 mm Hg, 95% CI -15.59 to -8.39, P <
      0.00001) and DBP (WMD = -5.28 mm Hg, 95% CI, -8.13 to -2.42, P = 0.0003) compared
      with antihypertensive drugs alone. No serious adverse events were reported.The
      meta-analysis suggests that qigong is an effective therapy for hypertension.
      However, more rigorously designed randomized controlled trials with long-term
      follow-up focusing on hard clinical outcomes are required to confirm the results.

PMID- 25569653
TI  - Preoperative factors predicting intraoperative blood loss in female patients with
      adolescent idiopathic scoliosis.
AB  - In this article, a retrospective analysis of 161 female patients with adolescent
      idiopathic scoliosis (AIS) is performed who underwent posterior correction and
      fusion using all-pedicle screw instrument.The aim of this article is to find out
      preoperative factors that influence intraoperative blood loss (IOBL) in female
      patients with AIS.The IOBL in posterior correction and fusion surgery for
      patients with idiopathic scoliosis greatly varies. The variables affecting the
      IOBL also greatly vary among different studies.Medical records of all female
      patients with AIS who underwent posterior correction and fusion operations using
      the all-pedicle screw system in our hospital from January 2012 to January 2014
      were reviewed. Patients with irregular menstruation, who underwent osteotomy, and
      using coagulants were excluded. Preoperative clinical data, including patient
      age, height, weight, Risser sign, day after last menstruation, major curve Cobb
      angle, fulcrum-bending Cobb angle, curve flexibility index, sagittal thoracic
      Cobb angle, sagittal lumbar Cobb angle, albumin, hemoglobin, platelet, activated
      partial thromboplastic time (APTT), prothrombin time, thrombin time, fibrinogen,
      fusion level, menstrual phase, and blood type, were collected. Data were further
      analyzed using multiple linear regression with forward elimination.A total of 161
      patients were included in this study. The mean IOBL was 933.98 +/- 158.10 mL (500
      2000 mL). Forward selection showed that fulcrum-bending Cobb angle, fusion level,
      Risser sign, APTT, fibrinogen, and menstrual phase were the preoperative factors
      that influenced the IOBL in female patients with AIS. Equation of IOBL was built
      by multiple linear regression: IOBL = -966.228 + 54.738 Risser sign + 18.910
      fulcrum-bending Cobb angle + 114.737 fibrinogen + 21.386 APTT - 71.312 team 2 -
      177.985 team 3 - 165.082 team 4 + 53.470 fusion level. R = 0.782.Operation for
      patients with AIS was featured by large IOBL. Large fulcrum-bending Cobb angle,
      the number of level fused, higher Risser sign, high APTT, high preoperative blood
      fibrinogen concentration, and premenstrual phase predicted higher IOBL. 

PMID- 25569654
TI  - Sedation and analgesia with fentanyl and etomidate for intrathecal injection in
      childhood leukemia patients.
AB  - In this study, we tried to find a safe as well as fast effective treatment for
      sedation and analgesia for intrathecal injection in childhood leukemia patients,
      relieving treatment difficulties and pain, increasing the success rate of single
      intrathecal injection.The patients were divided into the experimental group
      (fentanyl combined with etomidate) and the control group (lidocaine only)
      randomly. The experimental group was given fentanyl 1 to 2 MUg/kg intravenously
      first, then etomidate 0.1 to 0.3 mg/kg intravenously after the pipe washed. The
      patients younger than 1.5 years or who did not achieve satisfied sedative and
      analgesic situation received an additional time of etomidate (0.1-0.3 mg/kg). The
      patients were given oxygen at the rate of 4-5 L/min during the whole operation,
      and the finger pulse oximeter was used simultaneously to detect the changes in
      heart rate (HR) and blood oxygen saturation (SpO2). The doctors who performed the
      procedures assessed the quality of sedation and analgesia.In the experimental
      group, the patients' HR increased slightly after given fentanyl combined with
      etomidate. The patients' SpO2 was stable. Most patients achieved a good sedative
      and analgesic state within 1 to 2 minutes, and no case of respiration depression
      or cardiac arrhythmias occurred during the whole operation. The wake-up time was
      55.42 +/- 20.62 min. In the control group, the patients were not very cooperative
      during the intrathecal injection, which made the procedures very difficult.During
      intrathecal injection, pain obviously reduced and the success rate of single
      lumbar puncture increased. It is safe and effective to apply fentanyl combined
      with etomidate for sedation and analgesia. 

PMID- 25569656
TI  - Hepatocellular carcinoma with bile duct tumor thrombus: a clinicopathological
      analysis of factors predictive of recurrence and outcome after surgery.
AB  - Although hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is a
      rare entity, most patients experience tumor recurrence even after curative
      resection and the prognosis remains dismal. This study aimed to analyze the
      clinicopathological risk factors for recurrence and poor outcome after surgical
      treatment of HCC with BDTT.Clinicopathological data of 37 patients with HCC and
      BDTT who underwent surgical treatment from July 2005 to June 2012 at the authors'
      hospital were reviewed retrospectively. Prognostic factors and potential risk
      factors for recurrence were assessed by Cox proportional hazard model and binary
      logistic regression model, respectively.Among the 37 patients, anatomical and
      nonanatomical liver resection was performed in 26 and 11 patients, respectively.
      The resection was considered curative in 19 patients and palliative in 18
      patients. Also, 21 cases had tumor recurrence after operation and 7 cases of them
      were reoperated. Multivariate binary logistic regression model revealed that
      surgical curability was the only independent risk factor associated with
      postoperative tumor recurrence (P = 0.034). In addition, postoperative overall
      survival rates at 1, 2, and 3 years were 64.2%, 38.9%, and 24.3%, respectively.
      Cox multivariate analysis indicated that surgical curability and tumor recurrence
      were independent prognostic factors for both overall survival and recurrence-free
      survival (P < 0.05).Although patients with HCC and BDTT had a relatively high
      rate of early recurrence after surgery, relatively favorable long-term outcome
      after curative hepatic resection could be achieved. Therefore, extensive and
      curative surgical treatment should be recommended when complete resection can be
      achieved and liver functional reserve is satisfactory. 

PMID- 25569657
TI  - Extraosseous benign notochordal cell tumor originating in the lung: a case
      report.
AB  - Benign notochordal cell tumors (BNCTs) are tumors originating in the axial
      skeleton, where chordomas occur. Although very rare, some cases of extraosseous
      chordoma, such as in the soft tissue and lungs, have been reported. We report a
      case of a primary tumor showing the notochordal characteristics of BNCTs within
      the axial skeleton.An asymptomatic 57-year-old woman presented with an abnormal
      shadow on her chest radiograph; chest computed tomography revealed a well-defined
      round nodule. The resected sample tissue contained a jelly-like small nodule.
      Histologically, it was identified as a BNCT, based on minimal nuclear atypia,
      extremely low mitotic activity within the tumor cells lying in a sheet-like
      arrangement, and focal immunopositivity for brachyury.This is the third case
      report of BNCT originating in the lungs; BNCTs are considered asymptomatic tumors
      that are identified by using highly developed chest imaging technology; however,
      our findings also suggest that these notochordal tumors may potentially originate
      from extraosseous sites that lack ideal precursor cells. Our case suggests that
      notochordal tumors can arise from organs that are unrelated to known notochordal
      development. 

PMID- 25569655
TI  - Cerebral venous thrombosis in paroxysmal nocturnal hemoglobinuria: a series of 15
      cases and review of the literature.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of
      hematopoietic stem cells characterized by hemolytic anemia, marrow failure, and a
      high incidence of life-threatening venous thrombosis. Cerebral venous system is
      the second most frequent location of thrombosis after hepatic veins. However,
      data about PNH-related cerebral venous thrombosis (CVT) are very scarce because
      of the rarity of both the disorders.We report a French study about PNH patients
      with CVT. Patients were recruited retrospectively, from the Societe Francaise
      d'Hematologie (SFH) registry of 465 patients with PNH; the Lariboisiere registry
      of 399 patients with CVT; and a direct contact with 26 French Hematology Units.
      We review cases reported since 1938 in the English and French language
      literature. We then compared patients of our series with cases from the
      literature, with non-PNH-related CVT cases from Lariboisiere registry, and with
      PNH patients without CVT from SFH registry.Fifteen patients were included between
      1990 and 2012. Most patients were women (12/15) and half of them presented
      associated hormonal venous thrombosis risk factors. Three patients had
      concomitant hepatic vein thrombosis. CVT was the first manifestation of PNH in 4
      patients. No major difference in CVT characteristics was found compared with non
      PNH-related CVT cases, except for a younger age at diagnosis in PNH patients (P <
      0.001). All patients were treated with anticoagulation therapy. One death
      occurred in acute stage. All surviving patients were independent 1 year after.
      Median survival time was 9 years. Recurrent thrombosis rate was 50% at 6 years,
      occurring in patients that did not have bone marrow transplantation or eculizumab
      therapy. Cases of death were mainly related to hepatic vein thrombosis.Prognosis
      of CVT was good in our series. However, these patients have a poor long-term
      prognosis due to PNH disease by itself. PNH treatment should be proposed as soon
      as possible to avoid recurrent thrombosis. Besides, inaugural CVT events
      encourage investigating PNH in case of cytopenia, hemolysis, abdominal veins
      thrombosis, or aplastic anemia history associated with the neurological
      complication. 

PMID- 25569658
TI  - Extreme values of hemoglobin a1c are associated with increased risks of chronic
      obstructive pulmonary disease in patients with type 2 diabetes: a competing risk
      analysis in national cohort of Taiwan diabetes study.
AB  - The purpose of this study was to evaluate the relationship between glycated
      hemoglobin (HbA1c) and chronic obstructive pulmonary disease (COPD) in patients
      with type 2 diabetes.We conducted a retrospective cohort study involving 45,753
      patients with type 2 diabetes, who participated in the National Diabetes Case
      Management Program in Taiwan. HbA1c at baseline and COPD events over the
      subsequent years were analyzed.After multivariate adjustment, the COPD risk
      increased among patients with HbA1c levels <6.0%, compared with that in patients
      with HbA1c levels ranging from 6.0% to 7.0% (hazard ratio: 1.19, 95% confidence
      interval (CI): 1.06-1.34). Similarly, high HbA1c levels (>=10%) were
      independently associated with COPD (1.19, 95% CI: 1.06-1.32). A U-shaped
      relationship was observed between HbA1c levels and COPD incidence.HbA1c levels
      lower than 6.0% and higher than 10% are associated with an increased risk of COPD
      in patients with type 2 diabetes. These findings suggest that meeting the
      recommended HbA1c targets might reduce the risk of COPD, but care should be taken
      not to pose risks to this population. 

PMID- 25569659
TI  - Environmental NO2 level is associated with 2-year mortality in patients
      undergoing peritoneal dialysis.
AB  - An ongoing issue related to global urbanization is the association of air
      pollution with increased incidences of morbidity and mortality. However, no in
      depth study has investigated this issue focusing on peritoneal dialysis (PD)
      patients. Therefore, this study assessed the effects of traffic-related air
      pollutants and other important mortality-associated factors on 2-year mortality
      in PD patients.A total of 160 PD patients were recruited in this 2-year
      retrospective observational study. Differences in air quality were analyzed with
      respect to the patients' living areas. The PD patients were categorized into 2
      groups according to high (n = 65) and low (n = 95) nitrogen dioxide (NO2)
      exposure. Demographic, hematological, nutritional, inflammatory, biochemical, air
      pollutants, and dialysis-related data were analyzed. Univariate and multivariate
      Cox regression analyses were used for 2-year mortality analysis.A total of 160 PD
      patients (38 men and 122 women) were enrolled. Fourteen patients (8.8%) died
      within 2 years; among them, the causes of death were infection (n = 10),
      malignancy (n = 1), and cardiovascular events (n = 3). Among the 10 patients who
      died from infection, 5, 4, and 1 died from pneumonia, PD-related peritonitis, and
      sepsis of unknown origin, respectively. All patients who died from pneumonia were
      living in high environmental NO2 exposure areas. Multivariate Cox regression
      analysis showed that age (hazard ratio [HR] 1.073, 95% confidence interval [CI]
      [1.013-1.137]; P = 0.017), white blood cell count (HR 1.41, 95% CI [1.116-1.781];
      P = 0.004), log normalized protein nitrogen appearance (HR 0.0001, 95% CI [0
      0.073]; P = 0.005), high cardiothoracic ratio (HR 14.28, 95% CI [1.778-114.706];
      P = 0.012), and high environmental NO2 exposure (HR 3.776, 95% CI [1.143-12.47];
      P = 0.029) were significantly associated with 2-year mortality.PD patients with
      high environmental NO2 exposure had a higher 2-year mortality rate than those
      with low exposure. Therefore, air pollution may be associated with 2-year
      mortality in such patients. 

PMID- 25569660
TI  - Association between early Helicobacter pylori eradication and a lower risk of
      recurrent complicated peptic ulcers in end-stage renal disease patients.
AB  - End-stage renal disease (ESRD) patients exhibit an increased incidence of peptic
      ulcer disease. Helicobacter pylori plays a central role in the development of
      peptic ulcers. The effect of early H pylori eradication on the recurrence of
      complicated peptic ulcer disease in ESRD patients remains unclear. The aim of the
      present study was to explore whether early H pylori eradication therapy in ESRD
      patients can reduce the risk of recurrent complicated peptic ulcers.We conducted
      a population-based cohort study and recruited patients with ESRD who had
      developed peptic ulcers. We categorized patients into early (time lag ?120 days
      after peptic ulcer diagnosis) and late H pylori eradication therapy groups. The
      Cox proportional hazards model was used. The endpoint was based on
      hospitalization for complicated recurrent peptic ulcers.The early and late H
      pylori eradication therapy groups consisted of 2406 and 1356 ESRD patients,
      respectively, in a time lag of 120 days. After adjusting for possible
      confounders, the early eradication group exhibited a lower rate of complicated
      recurrent peptic ulcer disease (hazard ratio [HR] = 0.76, 95% confidence interval
      [CI] = 0.64-0.91, P = 0.003) in a time lag of ?120 days, but a similar rate of
      complicated recurrent peptic ulcer disease in time lags of ?1 year (HR = 0.97,
      95% CI 0.79-1.19, P = 0.758) and 2 years (HR = 1.11, 95% CI 0.86-1.44, P = 0.433)
      compared with the late eradication group.We recommend administering H pylori
      eradication within 120 days after peptic ulcer diagnosis to H pylori infected
      ESRD patients who have developed peptic ulcers. 

PMID- 25569661
TI  - Dosimetric comparative study of 3 different postoperative radiotherapy techniques
      (3D-CRT, IMRT, and RapidArc) for II-III stage rectal cancer.
AB  - Postoperative radiotherapy is critical for reducing local relapse for advanced
      rectal carcinoma but has many side effects. Our study compared the dose
      distribution of target volumes, protection of normal organs at risk (OAR), and
      monitor unit (MU) for 3 radiotherapy techniques (3-dimensional conformal
      radiation therapy [3D-CRT], intensity-modulated radiation therapy [IMRT], and
      RapidArc (Varian Medical Systems, Inc., Palo Alto, CA, USA)). The results
      advocate for the clinical application of RapidArc technique in the future.Thirty
      postoperative patients with rectal cancer were enrolled. The 3 radiotherapy plans
      mentioned above were designed for each patient. The target volume coverage
      indicators included average dose, conformity index (CI), and homogeneity index
      (HI) of planning tumor volume (PTV). OAR included the bladder, small intestine,
      colon, and bilateral proximal femurs. The 30 patients were divided into 3 groups
      (10 cases in each group) for postoperative radiotherapy with the 3D-CRT, IMRT, or
      RapidArc technique, respectively.Both the IMRT and RapidArc plans have a
      significantly higher average PTV dose and better CI and HI (P < 0.01) than 3D
      CRT. IMRT and RapidArc result in significantly lower doses of irradiation for all
      the OAR examined. Both the IMRT and RapidArc plans have a significantly lower V40
      of the bladder, small intestine, and colon than 3D-CRT (P < 0.01). The IMRT and
      RapidArc plans can also reduce the maximum dose (Dmax) for the left proximal
      femur, V30, and V40 of bilateral proximal femurs compared with 3D-CRT (P < 0.01).
      Compared with IMRT, RapidArc can further reduce the Dmax of the small intestine,
      the Dmax and V30 of the bilateral proximal femurs, and the V40 of the right
      proximal femur (P < 0.01). RapidArc reduces MU remarkably compared with IMRT (P <
      0.01). Regarding acute side effects, IMRT and RapidArc can greatly reduce the
      incidence of grade 3 radiation-induced cystitis and grade 2 enteritis.Both IMRT
      and RapidArc are better than 3D-CRT regarding PTV coverage and OAR protection.
      Furthermore, RapidArc is superior to IMRT regarding protection of the small
      intestine and bilateral proximal femurs and requires a reduced treatment time.
      RapidArc could be widely applied for postoperative radiotherapy for patients with
      IotaIota-IotaIotaIota stage rectal cancer. 

PMID- 25569662
TI  - Effect of endoscopic submucosal dissection for superficial esophageal neoplasms
      and risk factors for postoperative stricture.
AB  - Endoscopic submucosal dissection (ESD) enables wider tumor resection compared
      with endoscopic mucosal resection and en bloc resection of superficial esophageal
      neoplasms. However, ESD may cause difficult-to-treat stricture of the esophagus,
      and therefore, prediction of and measures against postoperative esophageal
      stricture are critical. The aim of this study was to evaluate the effect of ESD
      on superficial esophageal neoplasms and identify risk factors associated with
      esophageal stricture after ESD.This study included 165 lesions in 120 patients
      with superficial esophageal neoplasms, including cancer and neoplasia, who
      underwent ESD from 2009 to 2013.The complete resection rate of superficial
      esophageal neoplasms by ESD was 90.9%. After ESD, 22 subjects (18.3%) had
      symptomatic esophageal stricture, 12 (10.0%) had aspiration pneumonia of grade 2,
      and 7 (5.8%) had mediastinal emphysema of grade 2. Comparison of the 22 subjects
      with stricture with the 98 subjects without stricture showed significant
      differences in the rate of resection of >75% of the esophageal circumference,
      rate of whole circumference resection, and the required time for resection. The
      tumor size and the size of the resected tissue sample also differed between the 2
      groups. The groups did not differ in age, sex, alcohol intake, and smoking;
      location, macroscopic, and histological tumor findings; chest pain; or use of
      anticoagulants for comorbidities. In multivariate analysis, tumor size and whole
      circumference resection were independent risk factors for stricture. Furthermore,
      in 45 subjects with resection of >75% of the esophageal circumference, whole
      resection of the esophagus was the only independent risk factor for
      stricture.This study suggests that ESD has a strong therapeutic effect on
      superficial esophageal neoplasms; however, a greater extent of resection of the
      esophagus increases the risk of postoperative esophageal stricture. Preventive
      measures against development of postoperative stricture require further study. 

PMID- 25569663
TI  - Endoscopic versus open resection for small gastric gastrointestinal stromal
      tumors: safety and outcomes.
AB  - Endoscopic resection has been performed to treat small gastric neoplasms.
      However, this technique for small gastric gastrointestinal stromal tumors (GISTs)
      remains controversial. This study aims to compare the safety and surgical
      outcomes of endoscopic versus open resection of small gastric GISTs.The medical
      records of 54 consecutive gastric GISTs patients with tumor size of <=2 cm, who
      were surgically treated with endoscopic resection (endoscopic group) or open
      surgery (laparotomy group) in a single institution from March 2010 to June 2014,
      were retrospectively analyzed. The clinical and tumor characteristics, surgical
      safety, and tumor-related outcomes were evaluated.Of 54 patients, 32 and 22
      patients underwent endoscopic resection and laparotomy, respectively. Patients
      who underwent endoscopic resection yielded a significantly shorter hospital stay
      compared with patients who underwent laparotomy (P < 0.001). Compared with
      patients in the endoscopic group, patients in the laparotomy group had more
      intraoperative blood loss (P < 0.001), had longer nasogastric tube retention (P <
      0.001), and required longer operative time (P < 0.001). More laparotomy patients
      required postoperative analgesic drugs than those in the endoscopic group (n = 9
      vs 4; P = 0.016). Gastric perforation occurred in 1 case during operation in the
      endoscopic group. Patients who underwent these 2 procedures did not differ with
      respect to tumor size (P = 0.168), perioperative transfusion (P = 1.000),
      reoperation (P = 1.000), early satiety (P = 0.560), and postoperative bleeding (P
      = 1.000). With a median follow-up time of 34.5 months, 1 high-risk patient in
      each group experienced tumor recurrence/metastasis postoperatively.The endoscopic
      procedure allows safe resection with good surgical outcomes for small gastric
      GISTs compared with laparotomy. Moreover, larger randomized controlled trials are
      warranted to confirm endoscopic application for small gastric GISTs. 

PMID- 25569664
TI  - Gastrointestinal bleeding and anticoagulant or antiplatelet drugs: systematic
      search for clinical practice guidelines.
AB  - Gastrointestinal (GI) bleeding is a frequently encountered and very serious
      problem in emergency room patients who are currently being treated with
      anticoagulant or antiplatelet medications. There is, however, a lack of clinical
      practice guidelines about how to respond to these situations. The goal of this
      study was to find published articles that contain specific information about how
      to safely adjust anticoagulant and antiplatelet therapy when GI bleeding
      occurs.The investigators initiated a global search on the PubMed and Google
      websites for published information about GI bleeding in the presence of
      anticoagulant or antiplatelet therapy. After eliminating duplicate entries, the
      medical articles that remained were screened to narrow the sets of articles to
      those that met specific criteria. Articles that most closely matched study
      criteria were analyzed in detail and compared to determine how many actual
      guidelines exist and are useful.We could provide only minimal information about
      appropriate therapeutic strategies because no articles provided sufficient
      specific advice about how to respond to situations involving acute GI bleeding
      and concurrent use of anticoagulant or antiplatelet drugs. Only 4 articles
      provided enough detail to be of any use in an emergency situation.Clinical
      practice guidelines and also clinical trials for GI hemorrhaging should be
      expanded to state in which situations the use of anticoagulant or antiplatelet
      drugs should be suspended and the medications should later be resumed, and they
      should state the level of risk for any particular action. 

PMID- 25569665
TI  - Long-term survival following pancreatectomy and s-1 chemotherapy for pancreatic
      acinar cell carcinoma with peritoneal dissemination: a case report and literature
      review.
AB  - Current case is the third report of S-1 chemotherapy against acinar cell
      carcinoma (ACC) of pancreas, and our patient has achieved the longest reported
      recurrence-free survival, longer than 6 years, despite the presence of
      disseminated nodules at laparotomy.A 77-year-old man presented with abdominal
      discomfort. Computed tomography showed a low-density tumor in the pancreas tail
      and the patient was referred for surgery. A 3-cm sized pancreatic tumor, with
      localized disseminated nodules, was detected on laparotomy. Distal pancreatectomy
      with concomitant resection of disseminated nodules was performed, and
      histopathological examination revealed an ACC. Oral S-1 chemotherapy was
      administered postsurgery, and the patient showed no sign of recurrence during 73
      months of follow-up. This is the first report of long-term survivor of pancreatic
      ACC with peritoneal dissemination, following pancreatectomy and S-1
      chemotherapy.Current case suggests a beneficial effect of S-1 chemotherapy in
      cases of ACC. 

PMID- 25569666
TI  - Systematic review with network meta-analysis: adjuvant chemotherapy for resected
      colorectal liver metastases.
AB  - There are 5 major adjuvant chemotherapies (ACTs) for hepatic metastases for
      colorectal cancer; however, the optimal treatment regimen remains inconclusive.
      Here, we aim to compare these therapies in terms of patient survival rate,
      intrahepatic recurrence rate, and adverse events.Different databases were
      searched for controlled trials up to June 30, 2014. The pooled hazards ratios for
      death and odds ratios (ORs) for intrahepatic recurrence and adverse events were
      estimated. A mean ranking and the probability of optimal therapeutic regime was
      obtained for each treatment analyzed in the network meta-analysis.Eleven eligible
      articles were included. Systemic chemotherapy (SCT) was ranked the most
      efficacious intervention among ACTs in both 1-year and 5-year survival; however,
      no statistical difference could be determined. Combination of bevacizumab (BEV)
      and hepatic arterial infusion (HAI) plus SCT was the most effective in preventing
      intrahepatic recurrence when compared with HAI alone (OR 1.21, 95% confidence
      interval [CI] 0.01-131.12), SCT (OR 2.37, 95% CI 0.03-234.16), HAI plus SCT (OR
      0.97, 95% CI 0.03-35.30), SCT plus irinotecan (OR 1.01, 95% CI 0.00-278.14) and
      observation alone (OR 0.83, 95% CI 0.01-59.53). BEV and HAI plus SCT provided the
      least survival benefit after both 1 and 5 years compared with remaining
      therapies, and also was ranked the regiment with the least favorable adverse
      event profile among ACTs.SCT may be the most efficacious intervention, however,
      the potential benefit should be carefully considered with the regime's associated
      toxicities. Combination of BEV and HAI plus SCT was effective in preventing
      intrahepatic relapse but was associated with the highest risk for adverse events
      in patients with resected hepatic metastases for colorectal cancer. 

PMID- 25569667
TI  - Cyclosporine for the treatment of HLTV-1-induced HAM/TSP: an experience from a
      case report.
AB  - HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) remains a
      challenging disease. Treatment options are scarce, and their safety and efficacy
      are currently a matter of concern.We present a case report describing our
      experience using cyclosporine in a patient with early HAM/TSP who started with a
      gait disturbance at Vall d'Hebron University Hospital (Barcelona) from August
      2012 to October 2013. After 62 weeks of treatment, clinical improvement was
      observed and proviral load diminished. No safety concerns were
      observed.Cyclosporine seems to be effective in new-onset HAM/TSP or in chronic
      HAM/TSP that develops a relapse. However, the duration and safety profile of this
      steroid-sparing therapy remain unknown and should be further investigated. 

PMID- 25569668
TI  - Exposure of drugs for hypertension, diabetes, and autoimmune disease during
      pregnancy and perinatal outcomes: an investigation of the regulator in Japan.
AB  - Assessment of perinatal effects of drug exposure during pregnancy after approval
      is an important issue for regulatory agencies. The study aimed to explore
      associations between perinatal outcomes and maternal exposure to drugs for
      chronic diseases, including hypertension, diabetes, and autoimmune disease.We
      reviewed 521 cases of adverse reactions due to drug exposure during pregnancy who
      were reported to the Pharmaceuticals and Medical Devices Agency, a regulatory
      authority in Japan. The primary outcomes were fetal and neonatal death and
      malformation of infants. Associations between perinatal outcomes and exposure to
      each drug category for hypertension, diabetes, and autoimmune disease were
      evaluated using logistic regression analysis.Of the 521 cases (maternal age: 15
      47 years; mean 32.3 +/- 5.5), fetal and neonatal deaths were reported in 159
      cases (130 miscarriage; 12 stillbirth; 4, neonatal death; and 13 abortion due to
      medical reasons), and malformations of infants were observed in 124 cases. In
      contrast to the trend of association between diabetes with or without medication
      and fetal and neonatal death (odds ratio [OR], 0.49; 95% confidence interval
      [CI], 0.17-1.36), exposure to oral antidiabetics tended to be associated with
      fetal and neonatal death (OR, 4.86; 95% CI, 0.81-29.2). Malformation tended to be
      correlated with exposure to angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers (OR, 2.98; 95% CI, 0.76-11.7). This association
      showed trends opposite to that of the association with hypertension itself (OR,
      0.42; 95% CI, 0.18-1.02) or overall antihypertensives (OR, 0.42; 95% CI, 0.15
      1.13). Occurrence of multiple malformations was associated with exposure to
      biologics (OR, 8.46; 95% CI, 1.40-51.1), whereas there was no significant
      association between multiple malformations and autoimmune disease with or without
      medication (OR 1.07; 95% CI, 0.37-3.06).These findings suggest that drugs of
      different categories may have undesirable effects when used during pregnancy.
      However, the regulatory database was not originally designed to evaluate the
      causal associations between drug exposure and adverse drug reactions. The
      limitations of spontaneous reporting systems should be carefully taken into
      account. Further studies are needed to elucidate the effects of individual drugs
      in each category on perinatal outcomes. 

PMID- 25569669
TI  - Long-term pegylated interferon-alpha-2a treatment for chronic hepatitis C in an
      elderly renal transplant recipient: case report and literature review.
AB  - Combination treatment of pegylated interferon (PEG-IFN) plus ribavirin for renal
      transplant recipients (RTRs) with hepatitis C virus (HCV) infection remains
      controversial, as it has been associated with a high risk of rejection, resulting
      in graft loss and a reduction in patient survival.We present a special case of an
      elderly RTR who experienced treatment of HCV infection 8 years after renal
      transplant. There was no rejection episode during or after PEG-IFN treatment. The
      patient first received a 24-week therapy and a further 60-week course due to
      relapse. Cessation of both courses corresponded to an achieved end-of-treatment
      response. However, HCV infection reappeared shortly after cessation of the 60
      week treatment period.This case highlights the safety of PEG-IFN therapy for
      elderly RTR and the potential importance of combination pretreatment for patients
      undergoing renal transplantation. 

PMID- 25569671
TI  - Energetic contributions from the cation and anion to the stability of carbon
      dioxide dissolved in imidazolium-based ionic liquids.
AB  - Cation and anion effects were investigated in the energetics of CO2 solvation in
      room-temperature ionic liquids. The solvation free energy in 1-n-butyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide ([C4mim][NTf2]) was
      calculated with three types of force fields by molecular dynamics simulations
      combined with the energy-representation (ER) method, and the interaction
      responsible for the CO2 stability was examined in terms of the average sum of the
      solute-solvent interaction energy and its electrostatic and van der Waals
      components. A key role of the van der Waals component was found for the cation
      contribution, and the electrostatic component was seen to be minor in the anion
      contribution. The solvation free energy of CO2 was also investigated in ionic
      liquids of the form 1-n-alkyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([Cnmim][NTf2]) with varying alkyl-chain
      lengths of n = 4, 6, 8, and 12 by the ER method. The free energy was found to
      depend weakly on n, in agreement with experiments, and the cation and anion
      contributions and the electrostatic and van der Waals interaction components
      acted similarly at all values of n examined. The alkyl-chain length was found not
      to affect the local structure around CO2 strongly, and its effect on the
      interaction energy with CO2 appeared mainly through the bulk density. 

PMID- 25569670
TI  - Genetic mapping of MAPK-mediated complex traits Across S. cerevisiae.
AB  - Signaling pathways enable cells to sense and respond to their environment. Many
      cellular signaling strategies are conserved from fungi to humans, yet their
      activity and phenotypic consequences can vary extensively among individuals
      within a species. A systematic assessment of the impact of naturally occurring
      genetic variation on signaling pathways remains to be conducted. In S.
      cerevisiae, both response and resistance to stressors that activate signaling
      pathways differ between diverse isolates. Here, we present a quantitative trait
      locus (QTL) mapping approach that enables us to identify genetic variants
      underlying such phenotypic differences across the genetic and phenotypic
      diversity of S. cerevisiae. Using a Round-robin cross between twelve diverse
      strains, we identified QTL that influence phenotypes critically dependent on MAPK
      signaling cascades. Genetic variants under these QTL fall within MAPK signaling
      networks themselves as well as other interconnected signaling pathways. Finally,
      we demonstrate how the mapping results from multiple strain background can be
      leveraged to narrow the search space of causal genetic variants. 

PMID- 25569673
TI  - A nanostructured conductive hydrogels-based biosensor platform for human
      metabolite detection.
AB  - The development of a scalable, low-cost, and versatile biosensor platform for the
      sensitive and rapid detection of human metabolites is of great interest for
      healthcare, pharmaceuticals, and medical science. On the basis of hierarchically
      nanostructured conducting polymer hydrogels, we designed a flexible biosensor
      platform that can detect various human metabolites, such as uric acid,
      cholesterol, and triglycerides. Owing to the unique features of conducting
      polymer hydrogels, such as high permeability to biosubstrates and rapid electron
      transfer, our biosensors demonstrate excellent sensing performance with a wide
      linear range (uric acid, 0.07-1 mM; cholesterol, 0.3-9 mM, and triglycerides, 0.2
      5 mM), high sensitivity, low sensing limit, and rapid response time (~3 s). Given
      the facile and scalable processability of hydrogels, the proposed conductive
      hydrogels-based biosensor platform shows great promise as a low-cost sensor kit
      for healthcare monitoring, clinical diagnostics, and biomedical devices. 

PMID- 25569672
TI  - Transcriptional control of an essential ribozyme in Drosophila reveals an ancient
      evolutionary divide in animals.
AB  - Ribonuclease P (RNase P) is an essential enzyme required for 5'-maturation of
      tRNA. While an RNA-free, protein-based form of RNase P exists in eukaryotes, the
      ribonucleoprotein (RNP) form is found in all domains of life. The catalytic
      component of the RNP is an RNA known as RNase P RNA (RPR). Eukaryotic RPR genes
      are typically transcribed by RNA polymerase III (pol III). Here we showed that
      the RPR gene in Drosophila, which is annotated in the intron of a pol II
      transcribed protein-coding gene, lacks signals for transcription by pol III.
      Using reporter gene constructs that include the RPR-coding intron from
      Drosophila, we found that the intron contains all the sequences necessary for
      production of mature RPR but is dependent on the promoter of the recipient gene
      for expression. We also demonstrated that the intron-coded RPR copurifies with
      RNase P and is required for its activity. Analysis of RPR genes in various animal
      genomes revealed a striking divide in the animal kingdom that separates insects
      and crustaceans into a single group in which RPR genes lack signals for
      independent transcription and are embedded in different protein-coding genes. Our
      findings provide evidence for a genetic event that occurred approximately 500
      million years ago in the arthropod lineage, which switched the control of the
      transcription of RPR from pol III to pol II. 

PMID- 25569675
TI  - A (99m)Tc-labeled misonidazole analogue: step toward a (99m)Tc-alternative to
      [18F]fluromisonidazole for detecting tumor hypoxia.
AB  - The PET radiopharmaceutical [(18)F]Fluromisonidazole ([(18)F]FMISO) is presently
      the agent of choice for the clinical imaging of tumor hypoxia. Considering the
      logistic advantages of (99m)Tc and wider availability of SPECT machines, a
      (99m)Tc-radiopharmaceutical for this purpose constitutes an attractive choice. In
      the work presented here, a misonidazole analogue was radiolabeled with
      (99m)Tc(CO)3 core and the complex was evaluated in Swiss mice bearing
      fibrosarcoma tumor. The results obtained are compared with the biodistribution of
      [(18)F]FMISO carried out in the same tumor-bearing animal model. Misonidazole
      (99m)Tc(CO)3 complex showed significant uptake and retention in tumor. Notably,
      the rate of clearance of misonidazole complex from the tumor was slower than that
      of [(18)F]FMISO. The maximum tumor/muscle ratio obtained with misonidazole
      (99m)Tc(CO)3 complex was significantly higher than that of [(18)F]FMISO. The
      study constitutes a positive step toward the development of a (99m)Tc-analogue of
      [(18)F]FMISO. 

PMID- 25569676
TI  - Former paediatrician thought he was "bomb proof" against sex charges, court
      hears.

PMID- 25569674
TI  - Effectiveness of routine BCG vaccination on buruli ulcer disease: a case-control
      study in the Democratic Republic of Congo, Ghana and Togo.
AB  - BACKGROUND: The only available vaccine that could be potentially beneficial
      against mycobacterial diseases contains live attenuated bovine tuberculosis
      bacillus (Mycobacterium bovis) also called Bacillus Calmette-Guerin (BCG). Even
      though the BCG vaccine is still widely used, results on its effectiveness in
      preventing mycobacterial diseases are partially contradictory, especially
      regarding Buruli Ulcer Disease (BUD). The aim of this case-control study is to
      evaluate the possible protective effect of BCG vaccination on BUD. METHODOLOGY:
      The present study was performed in three different countries and sites where BUD
      is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010
      through 2013. The large study population was comprised of 401 cases with
      laboratory confirmed BUD and 826 controls, mostly family members or neighbors.
      PRINCIPAL FINDINGS: After stratification by the three countries, two sexes and
      four age groups, no significant correlation was found between the presence of BCG
      scar and BUD status of individuals. Multivariate analysis has shown that the
      independent variables country (p = 0.31), sex (p = 0.24), age (p = 0.96), and
      presence of a BCG scar (p = 0.07) did not significantly influence the development
      of BUD category I or category II/III. Furthermore, the status of BCG vaccination
      was also not significantly related to duration of BUD or time to healing of
      lesions. CONCLUSIONS: In our study, we did not observe significant evidence of a
      protective effect of routine BCG vaccination on the risk of developing either BUD
      or severe forms of BUD. Since accurate data on BCG strains used in these three
      countries were not available, no final conclusion can be drawn on the
      effectiveness of BCG strain in protecting against BUD. As has been suggested for
      tuberculosis and leprosy, well-designed prospective studies on different existing
      BCG vaccine strains are needed also for BUD.

PMID- 25569677
TI  - General Motor Vehicle Drivers' Knowledge and Practices Regarding Drink Driving in
      Yinchuan and Guangzhou, China.
AB  - OBJECTIVE: Drink driving contributes to significant levels of injury and economic
      loss in China but is not well researched. This study examined knowledge, drink
      driving practices, and alcohol misuse problems among general drivers in Yinchuan.
      The objectives were to gain a better understanding of drink driving in Yinchuan,
      identify areas that need to be addressed, and compare the results with a similar
      study in Guangzhou. METHODS: This was a cross-sectional study with a survey
      designed to collect information on participants' demographic characteristics and
      their knowledge and practices in relation to drinking and driving. The survey was
      composed of questions on knowledge and practices in relation to drink driving and
      was administered to a convenience sample of 406 drivers. Alcohol misuse problems
      were assessed by using the Alcohol Use Disorders Identification Test (AUDIT).
      RESULTS: Males accounted for the main proportion of drivers sampled from the
      general population ("general drivers"). A majority of general drivers in both
      cities knew that drunk driving had become a criminal offense in 2011; however,
      knowledge of 2 legal blood alcohol concentration (BAC) limits was quite low.
      Fewer drivers in Yinchuan (22.6%) than in Guangzhou (27.9) reported having been
      stopped by police conducting breath alcohol testing at least once in the last 12
      months. The mean AUDIT score in Yinchuan (M = 8.2) was higher than that in
      Guangzhou (M = 7.4), and the proportion of Yinchuan drivers with medium or higher
      alcohol misuse problems (31.2%) was correspondingly higher than in Guangzhou
      (23.1%). In Yinchuan, males had a significantly higher AUDIT score than females
      (t = 3.454, P <.001), similar to Guangzhou. Multiple regression analyses were
      conducted on potential predictors of the AUDIT score (age, gender, monthly
      income, education level, years licensed, and age started drinking). There were
      significant individual contributions of gender (beta = 0.173, P =.09) and age at
      which drinking started (beta = 0.141, P =.033), but the overall model for
      Yinchuan was not significant, unlike Guangzhou. CONCLUSIONS: The results show
      that there are shortfalls in knowledge of the legislation and how to comply with
      it and deficiencies in police enforcement. In addition, there was evidence of
      drink driving and drink riding at high levels in both cities. Recommendations are
      made to address these issues.

PMID- 25569679
TI  - Effect of premedication regimen on infant pain and stress response to
      endotracheal intubation.
AB  - OBJECTIVE: (1) Evaluate the effect of different medications on pain and stress in
      neonates during nonemergent endotracheal intubation; (2) determine whether
      gestational age affects medication use; (3) determine whether better sedation
      results in a decrease in the number of attempts and/or total time for the
      procedure. STUDY DESIGN: Prospective observational study. Infant responses were
      measured using a clinical pain scale and blood glucose, a biochemical marker of
      acute stress. RESULT: A total of 166 infants were included, with adjusted
      gestational ages 24 to 44 weeks at the time of procedure. Premedication regimens
      included no medication ('none,' 27%), morphine (19%), morphine+midazolam (11%),
      fentanyl (14%), fentanyl+midazolam (19%) and midazolam alone (10%).
      Fentanyl+midazolam resulted in lower pain scores and less increase in blood
      glucose (both P<0.0001). No other regimen was different from 'none'. The most
      immature infants were less likely to receive premedication (P=0.023), although
      their pain scores and blood glucose responses were similar to more mature
      infants. None of the medication regimens reduced the total procedure time
      (P=0.55) or the number of attempts (P=0.145). CONCLUSION: Only fentanyl+midazolam
      significantly attenuated both the clinical pain score and the increase in blood
      glucose. Less mature infants had responses similar to those of more mature
      infants, but were less likely to receive premedication. None of the regimens
      decreased the time or number of attempts required for successful intubation.

PMID- 25569680
TI  - Labor induction utilizing the Foley balloon: a randomized trial comparing
      standard placement versus immediate removal.
AB  - OBJECTIVE: To compare time to delivery between two induction procedures. The
      Foley balloon is a mechanical method for cervical ripening. However, the device
      may also result in endogenous prostaglandin release following separation of the
      chorionic membrane and decidua. Prolonged Foley placement may therefore be
      unnecessary for successful labor induction. METHOD: Randomized controlled trial
      of labor induction at LAC+USC Medical Center between 2010 and 2013. Subjects were
      assigned to either (a) standard placement of the Foley balloon or (b) Foley
      balloon insufflation and immediate removal. Oxytocin was administered to all
      subjects not in active labor after 12 h. Delivery information and neonatal
      outcomes were documented and all patients were followed for 6 weeks for adverse
      events. RESULT: A total of 79 women were included in the analysis (37 standard
      and 42 immediate). Induction time was 8.6 h longer in the immediate removal group
      (23.5 vs 32.1, P=0.002), but the difference in delivery within 24 h did not meet
      the statistical significance (46.0 vs 28.6%, P=0.11). Similar rates of cesarean
      delivery, epidural use and abnormal APGAR scores were observed. After controlling
      for number of vaginal exams and duration of rupture, a decreased risk of
      infection was observed in the immediate removal group (odds ratio=0.08, 95%
      confidence interval=0.007 to 0.93, P=0.04). Further, when the analysis was
      stratified by parity, differences in induction time only persisted in nulliparous
      women. CONCLUSION: Immediate removal of the Foley balloon may lead to longer
      overall induction time, but a lower risk of infection. Parous women may be
      particularly good candidates for this type of induction.

PMID- 25569681
TI  - Volume guarantee pressure support ventilation in extremely preterm infants and
      neurodevelopmental outcome at 18 months.
AB  - OBJECTIVE: Compared with pressure-controlled ventilation (PCV), volume-targeted
      ventilation is associated with decreased neonatal complications, including the
      combined outcome of death or bronchopulmonary dysplasia. However, little is known
      about its effect on neurodevelopmental outcome. We evaluated the hypothesis that
      as compared with PCV, volume-targeted ventilation reduces the risk of the
      combined outcome of neurodevelopmental impairment or death in very low birth
      weight infants. STUDY DESIGN: We studied a cohort of extremely preterm infants
      managed with either volume guarantee pressure support ventilation (VGPSV; n=135)
      or PCV (n=135). Infants were evaluated at 18 months adjusted age with a
      standardized neurological examination and the Bayley Scales of Infant and Toddler
      Development-third edition. Logistic regression models were used to evaluate the
      association of ventilation mode and neurodevelopmental outcome. RESULT: Rates of
      pulmonary interstitial emphysema (odds ratio 0.6; 95% confidence limits: 0.4,
      0.8), hypotension (odds ratio: 0.7; 95% confidence limits: 0.5, 0.9) and
      mortality (odds ratio 0.45; 95% confidence limits: 0.22, 0.9) were lower among
      infants treated with VGPSV. The infants in the VGPSV group had a significantly
      shorter duration on mechanical ventilation compared with infants in the PCV group
      (log-rank test P<0.01). Seventy percent (155/221) of survivors were evaluated at
      18 months adjusted age. A trend towards benefit for the combined outcome of death
      or neurodevelopmental impairment was seen in the VGPSV group but did not reach
      statistical significance (odds ratio: 0.59; 95% confidence limits: 0.32, 1.08).
      CONCLUSION: VGPSV was associated with a decreased risk of short-term
      complications but not long-term developmental impairment in this modest-sized
      cohort.

PMID- 25569678
TI  - Viral activation of MK2-hsp27-p115RhoGEF-RhoA signaling axis causes cytoskeletal
      rearrangements, p-body disruption and ARE-mRNA stabilization.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious cause of several
      AIDS-related cancers, including the endothelial cell (EC) neoplasm Kaposi's
      sarcoma (KS). KSHV-infected ECs secrete abundant host-derived pro-inflammatory
      molecules and angiogenic factors that contribute to tumorigenesis. The precise
      contributions of viral gene products to this secretory phenotype remain to be
      elucidated, but there is emerging evidence for post-transcriptional regulation.
      The Kaposin B (KapB) protein is thought to contribute to the secretory phenotype
      in infected cells by binding and activating the stress-responsive kinase MK2,
      thereby selectively blocking decay of AU-rich mRNAs (ARE-mRNAs) encoding pro
      inflammatory cytokines and angiogenic factors. Processing bodies (PBs) are
      cytoplasmic ribonucleoprotein foci in which ARE-mRNAs normally undergo rapid 5'
      to 3' decay. Here, we demonstrate that PB dispersion is a feature of latent KSHV
      infection, which is dependent on kaposin protein expression. KapB is sufficient
      to disperse PBs, and KapB-mediated ARE-mRNA stabilization could be partially
      reversed by treatments that restore PBs. Using a combination of genetic and
      chemical approaches we provide evidence that KapB-mediated PB dispersion is
      dependent on activation of a non-canonical Rho-GTPase signaling axis involving
      MK2, hsp27, p115RhoGEF and RhoA. PB dispersion in latently infected cells is
      likewise dependent on p115RhoGEF. In addition to PB dispersion, KapB-mediated
      RhoA activation in primary ECs caused actin stress fiber formation, increased
      cell motility and angiogenesis; these effects were dependent on the activity of
      the RhoA substrate kinases ROCK1/2. By contrast, KapB-mediated PB dispersion
      occurred in a ROCK1/2-independent manner. Taken together, these observations
      position KapB as a key contributor to viral reprogramming of ECs, capable of
      eliciting many of the phenotypes characteristic of KS tumor cells, and strongly
      contributing to the post-transcriptional control of EC gene expression and
      secretion. 

PMID- 25569683
TI  - Nurse with Ebola virus remains in critical condition.

PMID- 25569682
TI  - Production of siderophores increases resistance to fusaric acid in Pseudomonas
      protegens Pf-5.
AB  - Fusaric acid is produced by pathogenic fungi of the genus Fusarium, and is toxic
      to plants and rhizobacteria. Many fluorescent pseudomonads can prevent wilt
      diseases caused by these fungi. This study was undertaken to evaluate the effect
      of fusaric acid on P. protegens Pf-5 and elucidate the mechanisms that enable the
      bacterium to survive in the presence of the mycotoxin. The results confirm that
      fusaric acid negatively affects growth and motility of P. protegens. Moreover, a
      notable increase in secretion of the siderophore pyoverdine was observed when P.
      protegens was grown in the presence of fusaric acid. Concomitantly, levels of
      enzymes involved in the biosynthesis of pyoverdine and enantio-pyochelin, the
      second siderophore encoded by P. protegens, increased markedly. Moreover, while
      similar levels of resistance to fusaric acid were observed for P. protegens
      mutants unable to synthesize either pyoverdine or enanto-pyochelin and the wild
      type strain, a double mutant unable to synthesize both kinds of siderophores
      showed a dramatically reduced resistance to this compound. This reduced
      resistance was not observed when this mutant was grown under conditions of iron
      excess. Spectrophotometric titrations revealed that fusaric acid binds not only
      Fe2+ and Fe3+, but also Zn2+, Mn2+ and Cu2+, with high affinity. Our results
      demonstrate that iron sequestration accounts at least in part for the deleterious
      effect of the mycotoxin on P. protegens. 

PMID- 25569686
TI  - Combining nanosecond and millisecond time scale techniques: determination of
      thermodynamic and kinetic data of primary alkyl amine cation radicals.
AB  - Primary alkyl amines are one of the most commonly used and effective reagents in
      CO2 capture. Most of the amines used for CO2 capture are recycled, but a minor
      portion of the amines are degraded after one electron oxidation process, leading
      to highly toxic substances. The combination of the complementary information
      obtained from photoinduced electron transfer (flash photolysis) and heterogeneous
      electron transfer (electrochemistry) appears to be very attractive to fully
      characterize the electron transfer reaction mechanism of reactive species in
      general, as well as for determining important thermodynamic properties, such as
      standard potentials (E degrees ) or pKa values. It is particularly difficult to
      determine these crucial data accurately in the cases of alkyl primary amines.
      Hence, in this manuscript we focus on the establishment of the several alkyl
      primary amines oxidation mechanism in organic aprotic solvents. In order to
      achieve this, this work combines information provided by flash photolysis
      (nanosecond), cyclic voltammetry (millisecond), and digital simulation (nanomile
      second). Moreover, the accuracy of the E degrees  values calculated using the
      nanosecond equilibrium method allows not only revising them, but also estimating
      new important thermodynamic data concerning the bond dissociation energies (BDEs)
      of ammonium cations (N(+)-H) and of the amine cation radicals (alpha-C-H), as
      well as their corresponding pKa values. 

PMID- 25569685
TI  - Novel recombinant multiepitope proteins for the diagnosis of asymptomatic
      leishmania infantum-infected dogs.
AB  - BACKGROUND: Visceral leishmaniasis is the most severe form of leishmaniasis.
      Worldwide, approximately 20% of zoonotic human visceral leishmaniasis is caused
      by Leishmania infantum, also known as Leishmania chagasi in Latin America.
      Current diagnostic methods are not accurate enough to identify Leishmania
      infected animals and may compromise the effectiveness of disease control.
      Therefore, we aimed to produce and test two recombinant multiepitope proteins as
      a means to improve and increase accuracy in the diagnosis of canine visceral
      leishmaniasis (CVL). METHODOLOGY/PRINCIPAL FINDINGS: Ten antigenic peptides were
      identified by CVL ELISA in previous work. In the current proposal, the coding
      sequences of these ten peptides were assembled into a synthetic gene.
      Furthermore, other twenty peptides were selected from work by our group where
      good B and T cell epitopes were mapped. The coding sequences of these peptides
      were also assembled into a synthetic gene. Both genes have been cloned and
      expressed in Escherichia coli, producing two multiepitope recombinant proteins,
      PQ10 and PQ20. These antigens have been used in CVL ELISA and were able to
      identify asymptomatic dogs (80%) more effectively than EIE-LVC kit, produced by
      Bio-Manguinhos (0%) and DPP kit (10%). Moreover, our recombinant proteins
      presented an early detection (before PCR) of infected dogs, with positivities
      ranging from 23% to 65%, depending on the phase of infection in which sera were
      acquired. CONCLUSIONS/SIGNIFICANCE: Our study shows that ELISA using the
      multiepitope proteins PQ10 and PQ20 has great potential in early CVL diagnosis.
      The use of these proteins in other methodologies, such as immunochromatographic
      tests, could be beneficial mainly for the detection of asymptomatic dogs.

PMID- 25569688
TI  - Libel law reform: a new era of free speech in science?

PMID- 25569684
TI  - Identification of HNRNPK as regulator of hepatitis C virus particle production.
AB  - Hepatitis C virus (HCV) is a major cause of chronic liver disease affecting
      around 130 million people worldwide. While great progress has been made to define
      the principle steps of the viral life cycle, detailed knowledge how HCV interacts
      with its host cells is still limited. To overcome this limitation we conducted a
      comprehensive whole-virus RNA interference-based screen and identified 40 host
      dependency and 16 host restriction factors involved in HCV entry/replication or
      assembly/release. Of these factors, heterogeneous nuclear ribonucleoprotein K
      (HNRNPK) was found to suppress HCV particle production without affecting viral
      RNA replication. This suppression of virus production was specific to HCV,
      independent from assembly competence and genotype, and not found with the related
      Dengue virus. By using a knock-down rescue approach we identified the domains
      within HNRNPK required for suppression of HCV particle production. Importantly,
      HNRNPK was found to interact specifically with HCV RNA and this interaction was
      impaired by mutations that also reduced the ability to suppress HCV particle
      production. Finally, we found that in HCV-infected cells, subcellular
      distribution of HNRNPK was altered; the protein was recruited to sites in close
      proximity of lipid droplets and colocalized with core protein as well as HCV plus
      strand RNA, which was not the case with HNRNPK variants unable to suppress HCV
      virion formation. These results suggest that HNRNPK might determine efficiency of
      HCV particle production by limiting the availability of viral RNA for
      incorporation into virions. This study adds a new function to HNRNPK that acts as
      central hub in the replication cycle of multiple other viruses. 

PMID- 25569690
TI  - Solid-supported cross-metathesis and a formal alkane metathesis for the
      generation of biologically relevant molecules.
AB  - Solid-phase synthetic strategies toward the generation of libraries of
      biologically relevant molecules were developed using olefin cross-metathesis as a
      key step. It is remarkably the formal alkane metathesis based on a one-pot,
      microwave-assisted, ruthenium-catalyzed cross-metathesis and reduction to obtain
      Csp3-Csp3 linkages.

PMID- 25569687
TI  - Genetic variation in the nuclear and organellar genomes modulates stochastic
      variation in the metabolome, growth, and defense.
AB  - Recent studies are starting to show that genetic control over stochastic
      variation is a key evolutionary solution of single celled organisms in the face
      of unpredictable environments. This has been expanded to show that genetic
      variation can alter stochastic variation in transcriptional processes within
      multi-cellular eukaryotes. However, little is known about how genetic diversity
      can control stochastic variation within more non-cell autonomous phenotypes.
      Using an Arabidopsis reciprocal RIL population, we showed that there is
      significant genetic diversity influencing stochastic variation in the plant
      metabolome, defense chemistry, and growth. This genetic diversity included loci
      specific for the stochastic variation of each phenotypic class that did not
      affect the other phenotypic classes or the average phenotype. This suggests that
      the organism's networks are established so that noise can exist in one phenotypic
      level like metabolism and not permeate up or down to different phenotypic levels.
      Further, the genomic variation within the plastid and mitochondria also had
      significant effects on the stochastic variation of all phenotypic classes. The
      genetic influence over stochastic variation within the metabolome was highly
      metabolite specific, with neighboring metabolites in the same metabolic pathway
      frequently showing different levels of noise. As expected from bet-hedging
      theory, there was more genetic diversity and a wider range of stochastic
      variation for defense chemistry than found for primary metabolism. Thus, it is
      possible to begin dissecting the stochastic variation of whole organismal
      phenotypes in multi-cellular organisms. Further, there are loci that modulate
      stochastic variation at different phenotypic levels. Finding the identity of
      these genes will be key to developing complete models linking genotype to
      phenotype. 

PMID- 25569689
TI  - Copper-catalyzed C(sp3)-OH cleavage with concomitant C-C coupling: synthesis of 3
      substituted isoindolinones.
AB  - Copper(II) trifluoromethanesulfonate (Cu(OTf)2) efficiently catalyzes the C-C
      coupling of 3-hydoxyisoindolinones with a variety of aryl-, heteroaryl-, and
      alkenylboronic acids to furnish C(3) aryl-, heteroaryl-, and alkenyl-substituted
      isoindolinones. The coupling reactions work smoothly in 1,2-dicholoroethane (DCE)
      reflux, to effect both inter- and intramolecular versions. This is the first
      report on C(sp(3))-OH cleavage with concomitant C-C coupling. The photolabile 2
      nitrobenzyl protecting group is most appropriate for promotion of the coupling
      reaction and for deprotection. The tetracyclic ring motif of the alkaloid
      neuvamine was prepared by applying the newly developed copper-catalyzed C-C
      coupling. 

PMID- 25569691
TI  - High throughput absorbance spectra of cancerous cells: a microscopic
      investigation of spectral artifacts.
AB  - FTIR spectroscopy was recently demonstrated to be a useful tool to obtain a
      unique fingerprint of the effects of several anticancer drugs on cells in
      culture. While FTIR spectroscopy appears to have a definite potential to sort
      anticancer drugs on the basis of the metabolic modifications they induced, the
      present challenge is to evaluate the drug-induced spectral changes in cancer
      cells on a larger scale. The coupling of FTIR spectroscopy with a high throughput
      screening extension could become a useful method to generate drug classifications
      based on their "modes of action". Practically, the robustness of this approach is
      jeopardized by the variability that can appear from one cell smear to the next.
      When a few cells are scattered on the support, strong scattering effects are
      observed and locally dense cell aggregates could result in non-linearity of the
      signal. A microscopic study using infrared imaging demonstrates that the mean HTS
      (96-well High Throughput Spectroscopy) spectra recorded on 96 well ZnSe plates
      are the averages of contributions characterized by a wide absorbance distribution
      and by Mie scattering effects which significantly vary from point to point.
      Spectrum quality is at its best at the highest cell concentrations, i.e. from 300
      000 to 400 000 cells per well, which present the best S/N and a relatively
      smaller Mie scattering effect. When the breast cancer cell line MDA-MB-231 was
      treated with four different polyphenols, spectra showed quite similar variations
      with respect to control spectra, with more intense variations for the quercetin
      and EGCG compared to resveratrol and capsaicin. Correction of the spectra with
      the RMieS algorithm improved their clustering according to the polyphenolic
      treatment. 

PMID- 25569692
TI  - Public healthcare systems should not pay for private profit.

PMID- 25569693
TI  - Response inhibition difficulties in preterm children aged 9-12 years: Relations
      with emotion and behavior.
AB  - Previous studies with children have demonstrated inhibition difficulties
      associated with prematurity, but the question of potentially catching up with a
      delay in inhibition processes before adolescence still remains. Moreover, preterm
      adolescents are more at risk than their term-born peers for presenting behavioral
      problems such as emotional difficulties and attention deficit/hyperactivity
      disorder. In addition to examining response inhibition, this study addressed, for
      the first time, the impact of an emotional context on response inhibition
      abilities and its relation to behavioral problems in late school-aged preterm
      children. Fifty-eight preterm children aged 9-12 years were compared with 61
      controls on two versions of a stop-signal task, the Delay Frustration Task, and
      the Strengths and Difficulties Questionnaire. Results showed general difficulties
      in inhibiting a response, rather than a specific impact of emotional context in
      preterm children. Compared with controls, these children exhibited more and
      longer button presses in a delay situation, as well as faster go reaction times
      associated with lower probability of inhibition in the stop-signal tasks. These
      difficulties reflected impulsivity and were associated with higher
      hyperactivity/inattention and conduct problems. Additionally, intrauterine growth
      restriction was found to be an additional perinatal risk factor for
      hyperactivity/inattention symptoms. These findings suggest that remaining
      inhibition difficulties in the preterm population at preadolescence could reveal
      increasing behavioral issues.

PMID- 25569694
TI  - Parental weight status and offspring cardiovascular disease risks: a cross
      sectional study of Chinese children.
AB  - INTRODUCTION: Prevalence of childhood obesity in China is increasing, and
      parental weight is a risk factor for the development of obesity in children. We
      examined the relationship of parental body weight status with risk of offspring
      cardiovascular disease (CVD) in Chinese children. METHOD: We conducted a cross
      sectional study in Wuhan, China, during May and June 2010. Parental body mass
      index (BMI) was calculated according to self-reported height and weight.
      Offspring CVD risk factors, including BMI, waist circumference, blood pressure,
      fasting glucose, triglycerides, high-density lipoprotein (HDL) cholesterol, low
      density lipoprotein (LDL) cholesterol, cardiorespiratory fitness (CRF), and
      metabolic risk score (MRS), were assessed through anthropometric measures, blood
      samples, and a CRF test. Multiple linear regression and analysis of covariance
      were used to examine the effects of maternal and paternal weight status on
      offspring CVD risks. RESULTS: A total of 580 Chinese children (339 boys and 241
      girls, mean [standard deviation] age, 9.6 [0.7] years) participated in the study.
      Maternal BMI was significantly associated with offspring elevated BMI (beta =
      0.134, P = .002), waist circumference (beta = 0.253, P = .04), and decreased CRF
      (beta = -0.134, P = .01). Paternal BMI was significantly associated with elevated
      offspring BMI (beta = 0.161, P < .001), waist circumference (beta = 0.404, P <
      .001), triglycerides (beta = 0.017, P = .03), MRS (beta = 0.084, P = .03), and
      decreased CRF (beta = -0.174, P < .001). BMI (P < .001), waist circumference (P <
      .001), and MRS (P < .05) were positively associated with additional
      overweight/obese parents, whereas CRF was negatively associated (P < .001).
      CONCLUSION: Parental weight status was significantly associated with increased
      risk of CVD in their children, and the association was stronger for paternal
      weight status.

PMID- 25569696
TI  - Exploring better links between clinics and communities to improve population
      health.

PMID- 25569695
TI  - Factors associated with daily consumption of sugar-sweetened beverages among
      adult patients at four federally qualified health centers, Bronx, New York, 2013.
AB  - INTRODUCTION: Consumption of sugar-sweetened beverages (SSBs) is associated with
      cardiovascular disease risk factors. This study examined the relationships
      between SSB consumption and demographic, health behavior, health service, and
      health condition characteristics of adult patients of a network of federally
      qualified health centers (FQHCs) in a low-income, urban setting. METHODS:
      Validated, standardized self-reported health behavior questions were incorporated
      into the electronic health record (EHR) and asked of patients yearly, at 4 FQHCs.
      We conducted cross-sectional analysis of EHR data collected in 2013 from 12,214
      adult patients by using logistic regression. RESULTS: Forty percent of adult
      patients consumed 1 or more SSBs daily. The adjusted odds ratios indicated that
      patients who consumed more than 1 SSB daily were more likely to be aged 18 to 29
      years versus age 70 or older, current smokers versus never smoking, eating no
      servings of fruits and/or vegetables daily or 1 to 4 servings daily versus 5 or
      more servings daily, and not walking or biking more than 10 blocks in the past 30
      days. Patients consuming 1 or more servings of SSBs daily were less likely to
      speak Spanish than English, be women than men, be diagnosed with type 2 diabetes
      versus no diabetes, and be diagnosed with hypertension versus no hypertension.
      CONCLUSION: SSB consumption differed by certain demographic characteristics,
      health behaviors, and health conditions. Recording SSB intake and other health
      behaviors data in the EHR could help clinicians in identifying and counseling
      patients to promote health behavior changes. Future studies should investigate
      how EHR data on patient health behavior can be used to improve the health of
      patients and communities.

PMID- 25569697
TI  - Is Sympathetic Chain Clipping for Hyperhidrosis a Reversible Procedure?

PMID- 25569698
TI  - Aortic Arch Reconstruction in Neonates with Biventricular Morphology: Increased
      Risk for Development of Recoarctation by Use of Autologous Pericardium.
AB  - BACKGROUND: The aim of this study was to analyze risk factors promoting
      development of recoarctation (Re-CoA) in neonates who survived aortic arch repair
      from an anterior approach. METHODS: Fifty consecutive neonates with biventricular
      morphology and ductal-dependent lower body perfusion who were discharged home
      following aortic arch repair with cardiopulmonary bypass between 2000 and 2012
      were retrospectively reviewed. Arch anatomy was either interruption (n = 10) or
      hypoplasia with coarctation (n = 40). Aortic arch reconstruction was performed by
      using patch material (bovine pericardium, n = 30, homograft, n = 10, or
      glutaraldehyde-treated autologous pericardium, n = 7), and three patients
      underwent direct end-to-side anastomosis. Antegrade cerebral and continuous
      myocardial perfusion was performed in 39 and 21 patients, respectively. Kaplan
      Meier freedom from Re-CoA was calculated. Morphologic and perioperative data
      indicating increased risk of Re-CoA by univariate analysis were included in
      multivariate Cox regression analysis. RESULTS: Mean follow-up was 5.3 +/- 4.1
      years. Re-CoA occurred in 13 patients and was treated successfully by balloon
      dilatation (n = 6) or surgery (n = 7). Freedom from Re-CoA after 1 and 5 years
      was 83 +/- 5 and 79 +/- 6%, respectively. Two patients died early after surgical
      repair of Re-CoA. The use of autologous pericardium for aortic arch augmentation
      was the only independent risk factor for development of Re-CoA (hazard ratio: 4.3
      [95% confidence interval: 1.2-16.1]; p = 0.028). CONCLUSION: Re-CoA following
      neonatal aortic arch surgery can be treated by balloon dilatation or surgery, if
      adequate. In this study, the risk for development of Re-CoA was independently
      increased by the use of autologous pericardium during initial arch repair.

PMID- 25569699
TI  - Outcome after surgery for acute aortic dissection type A in the elderly: a single
      center experience.
AB  - OBJECTIVES: Despite improvements in surgical and perfusion techniques, surgery
      for acute aortic dissection type A (AADA) remains associated with high mortality
      rates. The aim of this study was to evaluate outcome after surgery for AADA in
      elderly in comparison with the outcome in younger patients. METHODS: Between
      January 2004 and December 2012, 204 patients underwent operation for AADA. Of
      these, 65 patients were aged 70 years and older (elderly group; range, 70-85
      years) and 139 were younger than 70 years (younger group; range, 18-69 years).
      RESULTS: No significant differences were detected between the groups with regard
      to preoperative risk factors on admission. Significantly more number of elderly
      patients than younger underwent supracoronary replacement of the ascending aorta
      (93.8% versus 80.6%, p = 0.013). In comparison to the elderly patients, younger
      patients more frequently received complex surgery (Bentall and David operation).
      The mean extracorporeal circulation time (183 +/- 62 minutes versus 158 +/- 3
      minutes; p = 0.003) and the mean aortic cross-clamp time (100 +/- 45 minute
      versus 82 +/- 30 minute; p = 0.006) were significantly higher for younger
      patients. No significant differences in postoperative complications and major
      morbidity were observed. The operative mortality (elderly group 4.6% versus
      younger group 1.4%; p = 0.33) and 30-day mortality (elderly group 18.5% versus
      younger group 8.6%; p = 0.06) were without statistical significance between the
      groups. CONCLUSION: Surgery for AADA in the elderly resulted in acceptable
      mortality. Satisfactory outcomes should encourage the offering of surgery in
      these patients.

PMID- 25569700
TI  - German Heart Report 2013.
AB  - OBJECTIVES: The 25th German Heart Report provides a comprehensive analysis of
      morbidity and mortality in patients with selected heart diseases as well as
      services and care in cardiology and cardiac surgery in Germany during the period
      2011-2012. It is the result of a multidisciplinary collaboration between the
      German Heart Foundation, the German Cardiac Society, the German Society for
      Thoracic and Cardiovascular Surgery, and the German Society of Pediatric
      Cardiology and is based on data from different sources. In addition, trends of
      the period from 1995 to 2012 are presented. RESULTS: The trends in morbidity due
      to cardiac diseases in 2010 and previous years continued in 2011. Compared with
      data from 1995 to 2010, one can observe: . a slight decrease in ischemic heart
      disease in every age group.. . a distinct increase in valve diseases,
      predominantly at age >75 years.. . an increase in arrhythmias from the age of 45
      years on.. . an increase in cardiac failure, especially beyond the age of 75
      years.. Compared with data from 2009, the mortality rates in 2011 differ
      somewhat; there is: . a decrease in heart failure and coronary heart disease.. .
      no change in arrhythmias.. . a distinct increase in valvular heart diseases.. .
      an additional, small decrease in congenital heart defects.. These data are in
      agreement with findings from other Western countries. Coronary heart disease, the
      most frequent cardiac disease, has continuously decreased in frequency and
      mortality since 2000. The underlying reasons are discussed. CONCLUSION: This
      report is an important resource for all parties of the healthcare system
      regarding heart disease conditions and their treatment in Germany.

PMID- 25569701
TI  - Potential effect of the presence of gray crescent on analysis of optic disc and
      retinal nerve fiber layer defects-reply.

PMID- 25569702
TI  - Prevalent polymorphism in thyroid hormone-activating enzyme leaves a genetic
      fingerprint that underlies associated clinical syndromes.
AB  - CONTEXT: A common polymorphism in the gene encoding the activating deiodinase
      (Thr92Ala-D2) is known to be associated with quality of life in millions of
      patients with hypothyroidism and with several organ-specific conditions. This
      polymorphism results in a single amino acid change within the D2 molecule where
      its susceptibility to ubiquitination and proteasomal degradation is regulated.
      OBJECTIVE: To define the molecular mechanisms underlying associated conditions in
      carriers of the Thr92Ala-D2 polymorphism. DESIGN, SETTING, PATIENTS: Microarray
      analyses of 19 postmortem human cerebral cortex samples were performed to
      establish a foundation for molecular studies via a cell model of HEK-293 cells
      stably expressing Thr92 or Ala92 D2. RESULTS: The cerebral cortex of Thr92Ala-D2
      carriers exhibits a transcriptional fingerprint that includes sets of genes
      involved in CNS diseases, ubiquitin, mitochondrial dysfunction (chromosomal genes
      encoding mitochondrial proteins), inflammation, apoptosis, DNA repair, and growth
      factor signaling. Similar findings were made in Ala92-D2-expressing HEK-293 cells
      and in both cases there was no evidence that thyroid hormone signaling was
      affected ie, the expression level of T3-responsive genes was unchanged, but that
      several other genes were differentially regulated. The combined microarray
      analyses (brain/cells) led to the development of an 81-gene classifier that
      correctly predicts the genotype of homozygous brain samples. In contrast to Thr92
      D2, Ala92-D2 exhibits longer half-life and was consistently found in the Golgi. A
      number of Golgi-related genes were down-regulated in Ala92-D2-expressing cells,
      but were normalized after 24-h-treatment with the antioxidant N-acetylecysteine.
      CONCLUSIONS: Ala92-D2 accumulates in the Golgi, where its presence and/or ensuing
      oxidative stress disrupts basic cellular functions and increases pre-apoptosis.
      These findings are reminiscent to disease mechanisms observed in other
      neurodegenerative disorders such as Huntington's disease, and could contribute to
      the unresolved neurocognitive symptoms of affected carriers.

PMID- 25569703
TI  - Complete remission with sunitinib in a poor-risk patient with metastatic renal
      cell carcinoma: the fine balance between toxicity and efficacy.
AB  - Sunitinib represents a reasonable therapeutic option for first-line treatment of
      poor-risk metastatic renal cell carcinoma and the treatment should aim at the
      delicate balance between managing side effects to improve the toxicity profile
      and patient compliance to treatment while maintaining anticancer efficacy.
      Achievement of a complete response, although rare, is possible, even in poor-risk
      patients. Treatment discontinuation represents a viable alternative for both
      tumour biology and patients' quality of life. To date, no molecular markers have
      been identified with prognostic and/or predictive value for guiding therapeutic
      decisions. Further research should aim at gaining in-depth knowledge of renal
      cell carcinoma biology for a tailored personalized therapy. We report a case of
      poor-risk metastatic renal cell carcinoma, with Von Hippel-Lindau loss of
      function, which achieved and maintained a complete remission after first-line
      therapy with sunitinib by using a reduced dosage and a modified schedule of
      treatment. 

PMID- 25569705
TI  - A combination of 2D similarity search, pharmacophore, and molecular docking
      techniques for the identification of vascular endothelial growth factor receptor
      2 inhibitors.
AB  - The human vascular endothelial growth factor receptor-2 (VEGFR-2) has been an
      attractive target for the inhibition of angiogenesis. In the current study, we
      used a hybrid protocol of virtual screening methods to retrieve new VEGFR-2
      inhibitors from the Zinc-Specs Database (441 574 compounds). The hybrid protocol
      included the initial screening of candidates by comparing the 2D similarity to
      five reported top active inhibitors of 13 VEGFR-2 X-ray crystallography
      structures, followed by the pharmacophore modeling of virtual screening on the
      basis of receptor-ligand interactions and further narrowing by LibDOCK to obtain
      the final hits. Two compounds (AN-919/41439526 and AK-968/40939851) with a high
      libscore were selected as the final hits for a subsequent cell cytotoxicity
      study. The two compounds screened exerted significant inhibitory effects on the
      proliferation of cancer cells (U87 and MCF-7). The results indicated that the
      hybrid procedure is an effective approach for screening specific receptor
      inhibitors. 

PMID- 25569704
TI  - Safety of spinal radiotherapy in metastatic cancer patients receiving bevacizumab
      therapy: a bi-institutional case series.
AB  - We retrospectively assessed the outcome of patients receiving emergency spinal
      radiation therapy (RT) concurrently with bevacizumab. Clinical records of 18
      consecutive patients receiving emergency spinal RT for symptomatic vertebral
      metastases during the course of bevacizumab-based therapy were examined. Patients
      were receiving biweekly bevacizumab combined with paclitaxel (n=17) or with
      docetaxel/carboplatin (n=1) or as a single agent (n=1) for advanced metastatic
      carcinoma. RT was delivered at doses of 30 Gy in 10 fractions (n=8), 20 Gy in
      five fractions (n=9) or 18 Gy in nine fractions (n=1). In 10 patients (56%),
      irradiation field encompassed the thoracic vertebrae. The median time interval
      between the bevacizumab infusion and the RT course was 1.5 days (0-8 days). The
      median follow-up was 8.3 months (2 days-42 months). A clinical benefit of RT was
      reported in 13 patients (72%), including four patients with complete pain relief.
      Two of the three patients with neurological impairment at the time of RT
      experienced a partial improvement in their symptoms. No pain recrudescence was
      reported within the irradiated field after RT completion. All toxicities were
      mild to moderate, with no acute toxicity reported in 13 patients (72%). No RT
      disruption was necessary because of acute toxicity. No delayed toxicity was
      reported within RT fields among 11 patients with at least 6 months of follow-up.
      Spinal RT during the course of bevacizumab-based therapy was not associated with
      the occurrence of unexpected adverse effects. This suggests that emergency RT
      should not be contraindicated in these patients, provided that doses and
      treatment volumes are defined carefully. 

PMID- 25569706
TI  - Antiangiogenesis as the novel mechanism for justicidin A in the anticancer effect
      on human bladder cancer.
AB  - Justicidin A (JA) is one of the methanol extracts of Justicia procumbens and was
      reported to induce apoptosis and inhibit the proliferation of human colon cancer
      cells. Using bladder cancer as a paradigm, this study was designed to identify
      the novel molecular basis underlying the antiangiogenic activities of JA and its
      potential in cancer therapy. Human bladder cancer cell lines (TSGH8301 and RT4)
      and immortalized uroepithelial cell lines (E6 and E7) were chosen to investigate
      the efficacy of JA in cell proliferation, apoptosis, and angiogenesis in vitro.
      The biological effects of JA treatment in vivo were examined using a xenograft
      tumor model in SCID mice. JA showed a dose-dependent and time-dependent
      inhibition of cell proliferation on TSGH8301 cancer cells, with IC50 values
      determined to be 0.44 MUmol/l. Of interest, TSGH8301 cancer cells were more
      sensitive to JA than E7 immortalized uroepithelial cells, especially at lower
      concentrations. We further showed that JA inhibited the autocrine production of
      angiogenic factors and matrix-degrading enzymes in vitro and microvessel density
      in SCID mice in vivo (P< 0.01). Both differential cytotoxicity and angiogenesis
      inhibition of JA were confirmed by SCID mice experiments. Together, JA showed
      antiangiogenesis in vitro and in vivo through pleiotropic positive and negative
      regulators of angiogenesis molecules. The current investigation supports the
      potential of JA as an alternative chemoprevention agent for human bladder cancer.

PMID- 25569708
TI  - Improved memory for reward cues following acute buprenorphine administration in
      humans.
AB  - In rodents, there is abundant evidence for the involvement of the opioid system
      in the processing of reward cues, but this system has remained understudied in
      humans. In humans, the happy facial expression is a pivotal reward cue. Happy
      facial expressions activate the brain's reward system and are disregarded by
      subjects scoring high on depressive mood who are low in reward drive. We
      investigated whether a single 0.2mg administration of the mixed mu-opioid
      agonist/kappa-antagonist, buprenorphine, would influence short-term memory for
      happy, angry or fearful expressions relative to neutral faces. Healthy human
      subjects (n38) participated in a randomized placebo-controlled within-subject
      design, and performed an emotional face relocation task after administration of
      buprenorphine and placebo. We show that, compared to placebo, buprenorphine
      administration results in a significant improvement of memory for happy faces.
      Our data demonstrate that acute manipulation of the opioid system by
      buprenorphine increases short-term memory for social reward cues. 

PMID- 25569709
TI  - Transformation of oligomers of lipidated peptide induced by change in pH.
AB  - Oligomerization of lipidated peptides is of general scientific interest and is
      important in biomedical and pharmaceutical applications. We investigated the
      solution properties of a lipidated peptide, Liraglutide, which is one of the
      glucagon-like peptide-1 (GLP-1) agonists used for the treatment of type II
      diabetes. Liraglutide can serve as a model system for studying biophysical and
      biochemical properties of micelle-like self-assemblies of the lipidated peptides.
      Here, we report a transformation induced in Liraglutide oligomers by changing pH
      in the vicinity of pH 7. This fully reversible transformation is characterized by
      changes in the size and aggregation number of the oligomer and an associated
      change in the secondary structure of the constituent peptides. This
      transformation has quite slow kinetics: the equilibrium is reached in a course of
      several days. Interestingly, while the transformation is induced by changing pH,
      its kinetics is essentially independent of the final pH. We interpreted these
      findings using a model in which desorption of the monomer from the oligomer is
      the rate-limiting step in the transformation, and we determined the rate constant
      of the monomer desorption. 

PMID- 25569707
TI  - Using modelling to disentangle the relative contributions of zoonotic and
      anthroponotic transmission: the case of lassa fever.
AB  - BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the
      majority of new human pathogens. Following zoonotic transmission, the pathogen
      may already have, or may acquire, the ability to transmit from human to human.
      With infections such as Lassa fever (LF), an often fatal, rodent-borne,
      hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to
      human, human-to-human and even human-to-rodent transmission patterns are
      possible. Indeed, large hospital-related outbreaks have been reported. Estimating
      the proportion of transmission due to human-to-human routes and related patterns
      (e.g. existence of super-spreaders), in these scenarios is challenging, but
      essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      make use of an innovative modeling approach to analyze data from published
      outbreaks and the number of LF hospitalized patients to Kenema Government
      Hospital in Sierra Leone to estimate the likely contribution of human-to-human
      transmission. The analyses show that almost [Formula: see text] of the cases at
      KGH are secondary cases arising from human-to-human transmission. However, we
      found much of this transmission is associated with a disproportionally large
      impact of a few individuals ('super-spreaders'), as we found only [Formula: see
      text] of human cases result in an effective reproduction number (i.e. the average
      number of secondary cases per infectious case) [Formula: see text], with a
      maximum value up to [Formula: see text]. CONCLUSIONS/SIGNIFICANCE: This work
      explains the discrepancy between the sizes of reported LF outbreaks and a
      clinical perception that human-to-human transmission is low. Future assessment of
      risks of LF and infection control guidelines should take into account the
      potentially large impact of super-spreaders in human-to-human transmission. Our
      work highlights several neglected topics in LF research, the occurrence and
      nature of super-spreading events and aspects of social behavior in transmission
      and detection.

PMID- 25569710
TI  - Influencing feelings of cancer risk: direct and moderator effects of affectively
      laden phrases in risk communication.
AB  - Evidence is accumulating for the importance of feelings of risk in explaining
      cancer preventive behaviors, but best practices for influencing these feelings
      are limited. This study investigated the direct and moderational influence of
      affectively laden phrases in cancer risk messages. Two experimental studies were
      conducted in relation to different cancer-related behaviors--sunbed use (n = 112)
      and red meat consumption (n = 447)--among student and nonstudent samples.
      Participants were randomly assigned to one of two conditions: (a) a cognitive
      message using cognitively laden phrases or (b) an affective message using
      affectively laden phrases. The results revealed that affective phrases did not
      directly influence feelings of risk in both studies. Evidence for a moderational
      influence was found in Study 2, suggesting that affective information
      strengthened the relation between feelings of risk and intention (i.e.,
      participants relied more on their feelings in the decision-making process after
      exposure to affective information). These findings suggest that solely using
      affective phrases in risk communication may not be sufficient to directly
      influence feelings of risk and other methods need to be explored in future
      research. Moreover, research is needed to replicate our preliminary indications
      for a moderational influence of affective phrases to advance theory and practice.

PMID- 25569711
TI  - NBD-based fluorescent chemosensor for the selective quantification of copper and
      sulfide in an aqueous solution and living cells.
AB  - Chemosensors play important roles in cation and anion recognition in biological,
      industrial, and environmental processes. Although many efforts have been made to
      develop artificial fluorescent receptors for Cu(2+) and S(2-), their applications
      in the detection in bulk solutions are limited. In this work, we report a novel
      fluorescence chemosensor (NL) based on the 7-nitrobenz-2-oxa-1,3-diazole (NBD)
      fluorophore for the quantification of Cu(2+) and S(2-) in single intact cells. NL
      specifically binds to Cu(2+) in the presence of other competing cations, and
      evident changes in UV-vis and fluorescence spectra in HEPES buffer are noticed.
      Based on the displacement approach, the selective sense S(2-) with the in situ
      generated NL-Cu(2+) ensemble gives a remarkable recovery of fluorescence and UV
      vis absorption spectra. The detection limits of NL for Cu(2+) and NL-Cu(2+) for
      S(2-) were estimated to be 1.6 nM and 0.17 MUM, respectively. NL and the
      resultant complex NL-Cu(2+) exhibit low cytotoxicity and cell-membrane
      permeability, which makes them capable of Cu(2+) and S(2-) imaging and
      quantification in living MDA-MB-231 cells.

PMID- 25569714
TI  - Effect of covalent modification of graphene nanosheets on the electrical property
      and electromagnetic interference shielding performance of a water-borne
      polyurethane composite.
AB  - Flexible and lightweight graphene nanosheet (GN)/waterborne polyurethane (WPU)
      composites which exhibit high electrical conductivity and electromagnetic
      shielding performance were prepared. Covalently modifying GNs with aminoethyl
      methacrylate (AEMA; AEMA-GNs) through free radical polymerization effectively
      inhibited the restacking and aggregation of the GNs because of the -NH3(+)
      functional groups grafted on the AEMA-GNs. Moreover, the AEMA-GNs exhibited high
      compatibility with a WPU matrix with grafted sulfonated functional groups because
      of the electrostatic attraction, which caused the AEMA-GNs to homogeneously
      disperse in the WPU matrix. This homogeneous distribution enabled the GNs to form
      electrically conductive networks. Furthermore, AEMA-GNs with different amounts of
      AEMA segments were introduced into the WPU matrix, and the effects of the surface
      chemistry of the GNs on the electrical conductivity and EMI shielding performance
      of composites were investigated. AEMA-GN/WPU composites with a GN loading of 5
      vol % exhibited remarkable electrical conductivity (approximately 43.64 S/m) and
      EMI shielding effectiveness (38 dB) over the frequency of 8.2 to 12.4 GHz. 

PMID- 25569712
TI  - From bright ideas to tools: the case of malaria.

PMID- 25569713
TI  - Technological aspects of delivering cryotherapy for prostate cancer.
AB  - Since the era of prostate specific antigen (PSA) testing, there has been a stage
      and grade migration seen with prostate cancer along with a reduction in
      mortality. Subsequently, concerns have been raised about the over treatment of
      patients following the diagnosis of localized prostate cancers. Cryotherapy, in
      which extremely low temperatures induce cell death via multiple mechanisms, has
      seen a drastic improvement in its technology since the 1800s. Such advances have
      improved oncological outcomes while reducing complication rates. Furthermore,
      technological advances have allowed the development of focal cryotherapy which
      aims to reduce morbidity associated with more radical whole-gland therapies.
      There is growing evidence that focal cryotherapy provides good oncological and
      morbidity rates when compared with traditional radical/whole-gland therapies. 

PMID- 25569715
TI  - Photoluminescence quenching and charge transfer in artificial heterostacks of
      monolayer transition metal dichalcogenides and few-layer black phosphorus.
AB  - Transition metal dichalcogenides monolayers and black phosphorus thin crystals
      are emerging two-dimensional materials that demonstrated extraordinary
      optoelectronic properties. Exotic properties and physics may arise when atomic
      layers of different materials are stacked together to form van der Waals solids.
      Understanding the important interlayer couplings in such heterostructures could
      provide avenues for control and creation of characteristics in these artificial
      stacks. Here we systematically investigate the optical and optoelectronic
      properties of artificial stacks of molybdenum disulfide, tungsten disulfide, and
      black phosphorus atomic layers. An anomalous photoluminescence quenching was
      observed in tungsten disulfide-molybdenum disulfide stacks. This was attributed
      to a direct to indirect band gap transition of tungsten disulfide in such stacks
      while molybdenum disulfide maintains its monolayer properties by first-principles
      calculations. On the other hand, due to the strong build-in electric fields in
      tungsten disulfide-black phosphorus or molybdenum disulfide-black phosphorus
      stacks, the excitons can be efficiently splitted despite both the component
      layers having a direct band gap in these stacks. We further examine
      optoelectronic properties of tungsten disulfide-molybdenum disulfide artificial
      stacks and demonstrate their great potentials in future optoelectronic
      applications. 

PMID- 25569717
TI  - Editorial: promoting equity in health: what role for courts?
AB  - One of the most significant transformations to occur in the landscape of
      struggles for health justice since this journal was originally launched relates
      to the increasing judicialization of health-related rights, and economic, social,
      and cultural rights (ESC rights) more broadly. Indeed, the articles in this issue
      go far toward debunking outdated conceptions about health rights as merely
      "programmatic rights," which are not justiciable. Over the last 20 years, and
      increasingly in the last decade, we have seen that health and related rights are
      in fact being enforced by courts around the world, from South America to South
      Asia, Eastern Europe to East Africa. And increasingly, even in low-income
      countries, important demands for health-related entitlements are being framed in
      terms of legally enforceable claims. 

PMID- 25569716
TI  - Conversion of the LIMA1 tumour suppressor into an oncogenic LMO-like protein by
      API2-MALT1 in MALT lymphoma.
AB  - MALT1 is the only known paracaspase and is a critical mediator of B- and T-cell
      receptor signalling. The function of the MALT1 gene is subverted by oncogenic
      chimeric fusions arising from the recurrent t(11;18)(q21;q21) aberration, which
      is the most frequent translocation in mucosa-associated lymphoid tissue (MALT)
      lymphoma. API2-MALT1-positive MALT lymphomas manifest antibiotic resistance and
      aggressive clinical behaviour with poor clinical outcome. However, the mechanisms
      underlying API2-MALT1-induced MALT lymphomagenesis are not fully understood. Here
      we show that API2-MALT1 induces paracaspase-mediated cleavage of the tumour
      suppressor protein LIMA1. LIMA1 binding by API2-MALT1 is API2 dependent and
      proteolytic cleavage is dependent on MALT1 paracaspase activity. Intriguingly,
      API2-MALT1-mediated proteolysis generates a LIM domain-only (LMO)-containing
      fragment with oncogenic properties in vitro and in vivo. Importantly, primary
      MALT lymphomas harbouring the API2-MALT1 fusion uniquely demonstrate LIMA1
      cleavage fragments. Our studies reveal a novel paracaspase-mediated oncogenic
      gain-of-function mechanism in the pathogenesis of MALT lymphoma. 

PMID- 25569718
TI  - In memoriam: Giulia Tamayo, 1958-2014.

PMID- 25569719
TI  - Four strategic pathways for the realization of the right to health through civil
      society actions: challenges and practical lessons learned in the Egyptian
      context.
AB  - This article examines four distinctly different, yet fully complementary,
      strategic pathways adopted by the Egyptian Initiative for Personal Rights (EIPR),
      an Egyptian independent human rights organization, in its practical efforts to
      protect and guarantee the realization of the right to health to all Egyptians. It
      reflects upon practical experiences, covering strategic options that include
      proposing new legislation to policy makers, participatory formulation of new laws
      from the ground up, public advocacy, coalition building, and litigation. It also
      examines several factors that affect the decision on which strategic pathway to
      follow. It reflects on the politico-economic settings, the presence of political
      will, the scope and extent of impacted stakeholders and the degree of complexity
      of the cause in question. 

PMID- 25569720
TI  - Litigating reproductive health rights in the Inter-American System: what does a
      winning case look like?
AB  - Remedies and reparation measures emerging from the Inter-American System of Human
      Rights in reproductive health cases have consistently highlighted the need to
      develop, and subsequently implement, non-repetition remedies that protect,
      promote, and fulfill women's reproductive health rights. Litigation outcomes that
      determine there have been violations of reproductive rights are regarded as a
      "win" for health rights litigation, but when implementation fails, is a "win"
      still a win? There has been considerable success in litigating reproductive
      health rights cases, yet the Inter-American Commission on Human Rights and the
      Inter-American Court of Human Rights are not adequately equipped to follow up on
      cases after they have been won. Successful and sustainable implementation of
      reproductive health rights law requires incorporation of non-repetition remedies
      in the form of legislation, education, and training that seeks to remodel
      existing social and cultural practices that hinder women's enjoyment of their
      reproductive rights. In order for a reproductive health rights case to ultimately
      be a "winner," case recommendations and decisions emerging from the Commission
      and Court must incorporate perspectives from members of civil society, with the
      ultimate goal being to develop measurable remedies that address underlying
      obstacles to domestic implementation. 

PMID- 25569721
TI  - Health rights in the balance: the case against perinatal shackling of women
      behind bars.
AB  - Rationalized for decades on security grounds, perinatal shackling entails the
      application of handcuffs, leg irons, and/or waist shackles to the incarcerated
      woman prior to, during, and after labor and delivery. During labor and delivery
      proper, perinatal shackling may entail chaining women to the hospital bed by the
      ankle, wrist, or both. Medically untenable, legally challenged, and ever
      controversial, perinatal shackling remains the standard of practice in most US
      states despite sustained two-decades-long efforts by health rights legal
      advocates, human rights organizations, and medical professionals. Herein we
      review the current statutory, regulatory, legal, and medical framework
      undergirding the use of restraints on pregnant inmates and explore potential
      avenues of redress and relief to this challenge. We also recognize the courage of
      the women whose stories are being told. If history is any guide, the collective
      thrust of domestic and international law, attendant litigation, dedicated
      advocacy, and strength of argument bode well for continued progress toward
      restraint-free pregnancies in correctional settings. 

PMID- 25569722
TI  - Sex workers, unite! (Litigating for sex workers' freedom of association in
      Russia).
AB  - The existing legal framework in Russia makes sex work and related activities
      punishable offenses, leaving sex workers stigmatized, vulnerable to violence, and
      disproportionally affected by HIV and other sexually transmitted infections. In
      2013, the Ministry of Justice, supported by the courts, refused registration and
      official recognition to the first all-Russia association of sex workers,
      referring to the fact that sex work is under administrative and criminal punitive
      bans and therefore the right of association for sex workers is unjustified. In
      light of international human rights standards, in particular the jurisprudence of
      the European Court of Human Rights, we examine in this paper whether the overall
      punitive legal ban on sex work in Russia is discriminatory. The government's
      positive obligations concerning discrimination against sex workers whose
      activities are consensual and between adults, and whose working conditions leave
      them among society's most vulnerable, should outweigh their punitive laws and
      policies around sex work. The scope of legal criminalization is narrow: it should
      apply only in exceptional cases where it is clearly justified. 

PMID- 25569723
TI  - Sanitation rights, public law litigation, and inequality: a case study from
      Brazil.
AB  - Public law litigation has been used in many places to advance human rights
      related to health. In Brazil, such lawsuits usually request that the government
      pay for pharmaceuticals to individuals. But could litigation play a role in
      shaping public health policies to benefit communities? To explore this question,
      this paper focuses on lawsuits involving determinants of health, namely water and
      sanitation public policies. This paper discusses the results of an empirical
      study of 258 Brazilian court orders, issued in a 10-year period, that address
      requests for sewage collection and treatment. The data show that the Brazilian
      judiciary is willing to improve access to sanitation services. However,
      litigation has addressed fewer than 177 out of the 2,495 Brazilian municipalities
      that lack both sewage collection and treatment systems, and lawsuits are
      concentrated in the richer cities, not in the poorest ones. This paper suggests
      that public law litigation can be used to foster public health policies similar
      to the way in which structural reform litigation and the experimentalism approach
      between courts and defendants have influenced public policies and achieved
      institutional reform in schools and prisons. However, greater effort is needed to
      target initiatives that would reach the most disenfranchised communities. 

PMID- 25569724
TI  - Health rights litigation and access to medicines: priority classification of
      successful cases from Costa Rica's constitutional chamber of the Supreme Court.
AB  - Although Costa Rica has no explicit constitutional right to health, its
      constitutional chamber of the Supreme Court (Sala IV) has become increasingly
      central to the resolution of many health care decisions. Some argue that courts'
      decisions about individuals' access to very expensive medications could upset the
      country's medical priorities and harm the state's general health care provision
      capacity. This article assesses whether health rights litigation concerning the
      right to medications leads to more fairness in access to medications in Costa
      Rica. We review randomly selected access to medicines cases successfully claimed
      at the Sala IV in 2008 and classify them into four priority groups using standard
      priority-setting criteria. We find that 2.7% of the successful cases fall into
      priority group I (highest priority), 27% in group II, 48.6% in group III, and
      21.6% in group IV (experimental treatment). Our analysis reveals a majority of
      successful health rights litigation for medications results in court-mandated
      provision of new, expensive drugs, many with only marginal benefits. More than
      70% of the successful cases evaluated concerned medications judged to be of low
      priority. Based on these cases, we cannot conclude that litigation leads to more
      fairness in access to medications. 

PMID- 25569725
TI  - Litigating the right to health: what can we learn from a comparative law and
      health care systems approach.
AB  - This article presents research demonstrating that the right to health plays
      different roles in different types of health systems. In high-income countries
      with tax-funded health systems, we usually encounter a lack of an enforceable
      right to heath. In contrast, rights play a more significant role in social health
      insurance/managed competition systems (which are present in a mixture of high
      income and middle-income countries). There is concern, for example in Colombia,
      that a high volume of rights litigation can challenge the very sustainability of
      a public health care system and distort resources away from those most in need.
      Finally, in middle-income countries with big gaps between a poor public health
      system and a rich private one, we are more likely to find an express
      constitutional right to health care (or one is inferred from, for example, the
      right to life). In some of these countries, constitutional rights were included
      as part of the transition to democracy and an attempt to address huge inequities
      within society. Here the scale of health inequities suggests that courts need to
      be bolder in their interpretation of health care rights. We conclude that in
      adjudicating health rights, courts should scrutinize decision-making through the
      lens of health equity and equality to better achieve the inherent values of
      health human rights. 

PMID- 25569726
TI  - Striking a balance: conscientious objection and reproductive health care from the
      Colombian perspective.
AB  - Conscientious Objection or conscientious refusal (CO) in access to reproductive
      health care is at the center of current legal debates worldwide. In countries
      such as the US and the UK, constitutional dilemmas surrounding CO in the context
      of reproductive health services reveal inadequate policy frameworks for balancing
      CO rights with women's rights to access contraception and abortion. The Colombian
      Constitutional Court's holistic jurisprudence regarding CO standards has applied
      international human rights norms so as to not only protect women's reproductive
      rights as fundamental rights, but to also introduce clear limits for the exercise
      of CO in health care settings. This paper reviews Latin American lines of
      regulation in Argentina, Uruguay, and Mexico City to argue that the Colombian
      Court's jurisprudence offers a strong guidance for future comprehensive policy
      approaches that aim to effectively balance tensions between CO and women's
      reproductive rights. 

PMID- 25569727
TI  - Health rights litigation pushes for accountability in clinical trials in India.
AB  - In 2009, around 24,000 girls in India were enrolled in a human papilloma virus
      (HPV) vaccination program that was later reviewed to investigate allegations of
      informed consent irregularities and inadequate monitoring. If the allegations are
      found to be correct, the clinical trial will have violated core human rights,
      including the right to health. Unfortunately, such irregularities are not unheard
      of in trials that are outsourced and off-shored. Those in charge of such clinical
      trials are, however, rarely held accountable before a court of law. As an example
      of health rights litigation, this article highlights proceedings before the
      Indian Supreme Court ("the Court"), which addresses the lack of protection of
      trial subjects. The Court already urged the Indian Government to advance the
      regulatory framework on clinical trials. However, full enforcement of relevant
      standards should not only address the role of state agencies, but also include
      private organizations conducting clinical trials and pharmaceutical companies
      that benefit from the results. An amicus curiae intervention in the ongoing
      Indian proceedings calls on the Supreme Court to clarify these standards and
      order European and American companies to comply. 

PMID- 25569729
TI  - Electrochemical and structural effects of in situ Li2O extraction from Li2MnO3
      for Li-Ion batteries.
AB  - Li2MnO3 is an attractive cathode material due to its low cost, nontoxicity and
      potentially high capacity. However, its electrochemical inactivity, its poor
      electronic conductivity, and uncertainty about its underlying mechanism have
      limited its development. In this work, an in situ technique for extraction of Li
      and O during deposition of the thin film cathode is developed to investigate
      structural and electrochemical effects in a controlled fashion. MnO2 has been
      observed in samples with severe O and Li deficiency (capacity of 115 mAh g(-1)),
      while Li2MnO3 cathodes with slight excess of O and Li (capacity of 225 mAh g(-1))
      can be synthesized by tuning growth conditions appropriately. Formation of a MnO2
      phase, especially in Li and O deficient structures, could be a possible reason
      for irreversible capacity loss in Li2MnO3 related materials. Further
      investigation into stoichiometric and microstructure variations enabled by this
      technique allows rapid investigation of Li2MnO3 as well as other Li-rich
      composites. 

PMID- 25569728
TI  - Right to health encompasses right to access essential generic medicines:
      challenging the 2008 Anti-Counterfeit Act in Kenya.
AB  - To what extent has the right to access generic HIV medication been implemented in
      Kenya for the 1.6 million people living with HIV? How does this relate to the
      right to health under international and national law? This paper examines a
      constitutional challenge brought to the High Court of Kenya in 2009 (the "Anti
      Counterfeit Case") against the Anti-Counterfeit Act of 2008, which the
      petitioners, all of whom were living with HIV, argued would affect their ability
      to access affordable and generic antiretroviral medication. They argued that this
      would amount to a violation of their right to life, dignity, and health. This
      case is particularly interesting because the new Kenyan Constitution came into
      force in 2010, after the case had been filed, and specifically provided for the
      right to health for all of Kenya's citizens, as well as giving direct effect to
      all international laws ratified by the Kenyan government. This paper follows the
      Anti-Counterfeit Case, which includes amendments filed by the petitioners
      following the new constitutional changes, the arguments by the different parties
      in the case, and the inappropriateness of counterfeit laws as measures to control
      substandard and falsified medicine. The case has resulted in the suspension of
      significant parts of the Anti-Counterfeit Act that would pose a challenge to
      parallel importation, and to the court issuing a directive that the sections be
      amended. The judgment is examined in detail, as are the broader implications of
      this case for other countries in Eastern Africa. 

PMID- 25569730
TI  - Efficient 11C-carbonylation of isolated aryl palladium complexes for PET:
      application to challenging radiopharmaceutical synthesis.
AB  - We describe the successful implementation of palladium-aryl oxidative addition
      complexes as stoichiometric reagents in carbonylation reactions with (11)CO to
      produce structurally challenging, pharmaceutically relevant compounds. This
      method enables the first (11)C-carbonyl labeling of an approved PET tracer,
      [(11)C]raclopride, for the dopamine D2/D3 receptor by carbonylation with
      excellent radiochemical purity and yield. Two other molecules, [(11)C]olaparib
      and [(11)C]JNJ 31020028, were efficiently labeled in this manner. The technique
      distinguishes itself from existing methods by the markedly improved purity
      profiles of the tracer molecules produced and provides access to complex
      structures in synthetically useful yields, hereby offering a viable alternative
      to other (11)C-labeling strategies. 

PMID- 25569731
TI  - Characterization and potential environmental implications of select Cu-based
      fungicides and bactericides employed in U.S. markets.
AB  - This exploratory study aimed to examine the extent and mineral speciation of
      nanosized Cu in two fungicide products (A and B) available in the U.S. markets.
      Electron microcopy results demonstrated the presence of spherical and
      polydisperse <100 nm Cu particles in product B. Other elements (e.g., Pb, Na, Ca,
      and S) were found in both products. Mineral speciation analysis indicated the
      dominance of spertiniite followed by cornetite and then malachite in product A.
      In product B, spertiniite and tenorite were the dominant Cu species followed by
      cornetite and malachite. Tenorite in product B (~30%, <450 nm) has the potential
      for stronger toxicological impacts relative to those of other Cu minerals in the
      tested products. For both products, the particle hydrodynamic diameter was
      impacted by changes in environmental parameters (pH, ionic strength, and
      background electrolyte) in Milli-Q water and humic acid suspensions. However, a
      minimal impact was observed in polyvinylpyrrolidone suspensions. The findings are
      critically important for estimating the fate and transport of Cu particles in
      different environmental scenarios as well as allowing a more accurate assessment
      of their risk that is largely impacted by chemical speciation and size.

PMID- 25569732
TI  - Body image dissatisfaction: clinical features, and psychosocial disability in
      inflammatory bowel disease.
AB  - BACKGROUND: Body image refers to a person's sense of their physical appearance
      and body function. A negative body image self-evaluation may result in
      psychosocial dysfunction. Crohn's disease and ulcerative colitis are associated
      with disabling features, and body image dissatisfaction is a concern for many
      patients with inflammatory bowel disease (IBD). However, no study has assessed
      body image and its comorbidities in patients with IBD using validated
      instruments. Our aim was to explore body image dissatisfaction in patients with
      IBD and assess its relationship with biological and psychosocial variables.
      METHODS: We studied 330 patients (median age, 36 yr; range, 18-83; 169 men) using
      quantitative and qualitative methods. Patients completed a self-administered
      questionnaire that included a modified Hopwood Body Image Scale, the Cash Body
      Image Disturbance Questionnaire, and other validated instruments. Clinical and
      disease activity data were also collected. RESULTS: Body image dissatisfaction
      was associated with disease activity (P < 0.001) and steroid treatment (P = 0.03)
      but not with immunotherapy (P = 0.57) or biological (P = 0.55) therapy. Body
      image dissatisfaction was also associated with low levels of general (P < 0.001)
      and IBD-specific (P < 0.001) quality of life, self-esteem (P < 0.001), and sexual
      satisfaction (P < 0.001), and with high levels of anxiety (P < 0.001) and
      depression (P < 0.001). Qualitative analysis indicated that patients were
      concerned about both physical and psychosocial consequences of body image
      dissatisfaction, including steroid side effects and impaired work and social
      activities. CONCLUSIONS: Body image dissatisfaction is common in patients with
      IBD, relates to specific clinical variables and is associated with significant
      psychological dysfunction. Its measurement is warranted as part of a
      comprehensive patient-centered IBD assessment.

PMID- 25569733
TI  - Risk for colorectal neoplasia in patients with inflammatory bowel disease and
      mucosa indefinite for dysplasia.
AB  - BACKGROUND: The management of colonic epithelial changes indefinite for dysplasia
      (IND) in patients with inflammatory bowel disease (IBD) remains controversial
      because of a paucity of published outcome data. METHODS: We analyzed data from 93
      patients with IBD who were IND and 52 IBD patients without dysplasia (controls)
      from the Department of Anatomic Pathology database at the Cleveland Clinic from
      1989 to 2004. Pathology reports, histologic slides, clinical features, and
      outcomes were reviewed. RESULTS: Twenty-two patients (23.7%) had surgical
      resections within 6 months of the IND assignment; of these, 6 had dysplasia
      (27.3%; 1 low-grade dysplasia and 5 high-grade dysplasia [HGD]). The remaining 71
      patients received regular colonoscopy examinations for a mean period of 98.6
      months; 18 patients developed dysplasia or carcinoma (25.2%; 10 low-grade
      dysplasia, 5 HGD, and 3 colorectal cancer). There was a mean interval of 53.9
      months between an IND assignment and identification of dysplasia or carcinoma.
      Histology review of 59 cases revealed 3.2 cases per 100 person-years for
      neoplasia (low-grade dysplasia, HGD, or colorectal cancer) and 1.5 cases per 100
      person-years for advanced neoplasia (HGD or colorectal cancer); these values were
      higher than those for controls (1.9 cases per 100 person-years for neoplasia and
      0.7 cases per 100 person-years for advance neoplasia; P = 0.1 and P = 0.2,
      respectively, for IND versus controls). Patients aged more than 44 years when
      they were found to be IND were more likely than younger patients to develop
      neoplasia (hazard ratio, 6.7; P = 0.01). CONCLUSIONS: Patients with IBD and IND
      are at significant risk for colorectal dysplasia and cancer. These patients
      should be closely followed.

PMID- 25569734
TI  - Saccharomyces cerevisiae CNCM I-3856 prevents colitis induced by AIEC bacteria in
      the transgenic mouse model mimicking Crohn's disease.
AB  - BACKGROUND: Adherent-invasive Escherichia coli (AIEC), which colonize the ileal
      mucosa of patients with Crohn's disease (CD), are able to adhere to and invade
      intestinal epithelial cells. Overexpression of the glycoprotein CEACAM6 on host
      cells favors AIEC attachment and inflammation. We investigated the ability of
      Saccharomyces cerevisiae CNCM I-3856 to inhibit AIEC adhesion and to reduce
      colitis. METHODS: Adhesion experiments were performed on T84 cells and on
      enterocytes from patients with CD with AIEC LF82 in the presence of S.
      cerevisiae. Colonization and symptoms of colitis were assessed in LF82-infected
      transgenic CEABAC10 mice treated with live S. cerevisiae or S. cerevisiae
      derivatives. Proinflammatory cytokines were quantified by enzyme linked
      immunosorbent assay. Intestinal permeability was assessed by measuring the 4 kDa
      dextran-FITC flux in the serum. RESULTS: S. cerevisiae strongly inhibited LF82
      adhesion to T84 cells and to the brush border of CD enterocytes. Yeasts decreased
      LF82 colonization and colitis in CEABAC10 mice and restored barrier function
      through prevention of the LF82-induced expression of pore-forming tight junction
      claudin-2 at the plasma membrane of intestinal epithelial cells. These effects
      were accompanied by a decrease in proinflammatory cytokines IL-6, IL-1beta, and
      KC release by the gut mucosa. Yeast derivatives exerted similar effects on LF82
      colonization and colitis demonstrating that yeast viability was not essential to
      exert beneficial effects. CONCLUSIONS: S. cerevisiae yeasts reduce colitis
      induced by AIEC bacteria in CEACAM6-expressing mice. Such a probiotic strategy
      could be envisaged in a subgroup of patients with CD abnormally expressing
      CEACAM6 at the ileal mucosa and therefore susceptible to being colonized by AIEC
      bacteria.

PMID- 25569735
TI  - Health-related quality of life in inflammatory bowel disease in a European-wide
      population-based cohort 10 years after diagnosis.
AB  - BACKGROUND: Chronic inflammatory bowel disease (IBD) negatively affects the
      patient's health-related quality of life (HRQoL). Only a few population-based
      studies have compared the HRQoL of patients with the background population. The
      aim of this study was to evaluate the HRQoL in a European cohort of patients with
      ulcerative colitis and Crohn's disease 10 years after diagnosis (European
      Collaborative study group of Inflammatory Bowel Disease) compared with the
      national background population in each country and to assess possible country
      specific differences. METHODS: Patients with IBD from 7 European countries were
      invited to a follow-up visit 10 years after their diagnosis of IBD. We assessed
      their clinical and demographic data, including the generic HRQoL questionnaire
      short form health survey-36. Countrywise comparison with the background
      population was performed with z-scores using the Cohen's effect size index.
      RESULTS: Seven hundred sixty-nine patients were eligible for the study. We
      registered statistically significant and clinically relevant decreases in the
      short form health survey-36 dimensional scores in patients with symptoms at the
      time of follow-up and for patients reporting sick leave during the previous year
      or having received disablement pension. In the Netherlands and Norway, there was
      a moderate difference between the patients with IBD and the background population
      for the general health dimension. CONCLUSIONS: Overall, the HRQoL was not reduced
      in the IBD cohort compared with the background populations. However, in addition
      to older age and female gender, current symptoms at follow-up, disablement
      pension, and sick leave during the previous year were significantly associated
      with a reduced HRQoL in patients with IBD.

PMID- 25569736
TI  - Body image dissatisfaction in patients with inflammatory bowel disease.
AB  - BACKGROUND: Despite the fact that the inflammatory bowel diseases (IBD) and their
      treatments may affect physical appearance, the effect of IBD on body image is
      poorly understood. The aims of this study were to determine whether body image
      dissatisfaction (BID) changes over time in patients with IBD and to examine the
      demographic and disease-related variables associated with decreased body image.
      METHODS: Adults aged 18 and above in the Ocean State Crohn's and Colitis Area
      Registry with at least 2 years of follow-up were eligible for this study. All
      patients were enrolled within 6 months of IBD diagnosis and followed
      prospectively. BID was assessed using a modified version of the Adapted
      Satisfaction With Appearance questionnaire. Total Adapted Satisfaction With
      Appearance scores and 2 subscores were calculated. To assess for changes over
      time, general linear models for correlated data were used for continuous
      outcomes, and generalized estimating equations were used for discrete outcomes.
      RESULTS: Two hundred seventy-four patients were studied. BID was found to be
      stable over time among men and women with IBD despite overall improvements in
      disease activity. No differences were found in BID according to IBD subtype.
      Female gender, greater disease activity, higher symptom burden, longer duration
      of steroid use, dermatologic and musculoskeletal manifestations of IBD, and
      ileocolonic disease location among patients with Crohn's disease were associated
      with greater BID. Greater BID was associated with lower health-related quality of
      life. CONCLUSIONS: BID remains stable in an incident cohort of IBD despite
      improved disease activity and is associated with lower health-related quality of
      life.

PMID- 25569737
TI  - Antibodies to infliximab are associated with lower infliximab levels and
      increased likelihood of surgery in pediatric IBD.
AB  - BACKGROUND: Adult studies suggest antibodies to infliximab (ATI) correlate with
      loss of response in inflammatory bowel disease but pediatric data are limited.
      METHODS: We conducted a cross-sectional study of trough infliximab levels and ATI
      in 134 pediatric and young adult patients receiving infliximab. At the time serum
      was obtained demographics, disease phenotype, duration of infliximab therapy, use
      of combination therapy (methotrexate or 6-mercaptopurine with infliximab), and
      surgery were recorded. RESULTS: Assays were performed on 134 subjects currently
      receiving infliximab (85 male; mean age, 17.3 +/- 4.3 years; 114 Crohn's disease
      and 20 ulcerative colitis). Infliximab use ranged from 12 days to 12 years:
      median 2.0 (interquartile range [1.1-4.3]) years. Twenty-seven of 134 (20%)
      patients had ATI >=5 U/mL. Of patients with ATI >=5 U/mL, 59% had infliximab
      levels <5 MUg/mL, compared with 14% of patients with ATI <5 U/mL (P < 0.001). Ten
      (7%) patients (9 Crohn's disease, 1 ulcerative colitis) underwent bowel
      resections after beginning infliximab infusions. Sixty percent who underwent
      surgery had ATI >=12 U/mL; in contrast, only 8% of patients who did not undergo
      surgery had ATI >=12 U/mL (P = 0.01). At the time of serum sampling, 50 (37%)
      patients were receiving combination therapy, compared with 84 (63%) on infliximab
      alone. Combination therapy at the time of serum sampling did not correlate with
      either increase infliximab levels or lower ATI compared with infliximab
      monotherapy. However, prior immunomodulator use was associated with lower
      antibody levels (P = 0.007). CONCLUSIONS: ATI correlates with reduction in
      infliximab level and a higher risk of surgery in patients with inflammatory bowel
      disease.

PMID- 25569738
TI  - Self-reported disability in patients with inflammatory bowel disease largely
      determined by disease activity and illness perceptions.
AB  - BACKGROUND: The inflammatory bowel disease (IBD) disability index has recently
      been introduced to measure patients' physical, psychological, familial, and
      social limitations associated with IBD. We assessed factors related to self
      reported disability and the relationship between disability and direct health
      care costs. METHODS: A large cohort of patients with Crohn's disease (CD) and
      ulcerative colitis (UC) was prospectively followed for 2 years by 3 monthly web
      based questionnaires. At 2 years, patients completed the IBD disability index,
      with lower score indicating more disability. Linear regression analysis was used
      to examine the impact of demographics, clinical characteristics, and illness
      perceptions on self-reported disability. Trends in direct health care costs
      across the disability severity groups minimal, mild, moderate, and severe, were
      tested. RESULTS: A total of 554 patients with CD and 424 patients with UC
      completed the IBD disability index (response rate, 45%). Both clinical
      characteristics and illness perceptions significantly contributed to self
      reported disability (45%-47%, P = 0.000 and 8%-12%, P = 0.000, respectively).
      Patients with CD scored lower on the self-reported IBD disability index than
      patients with UC (0.255 versus 3.890, P < 0.000), indicating more disability in
      patients with CD. Factors independently associated with higher self-reported
      disability rates were increased disease activity, illness identity (higher number
      of symptoms attributed to IBD), and stronger emotional response. Disease duration
      and disease phenotype were not associated with self-reported disability. Direct
      health care costs increased with the worsening of self-reported disability (P =
      0.000). CONCLUSIONS: More disability was reported by patients with CD than by UC.
      Self-reported disability in IBD was mainly determined by clinical disease
      activity and illness perceptions but not by disease duration or disease
      phenotype.

PMID- 25569739
TI  - Fecal calprotectin for evaluating postoperative recurrence of Crohn's disease: a
      meta-analysis of prospective studies.
AB  - BACKGROUND: Fecal calprotectin (FC) levels have been extensively reported to
      correlate with clinical and endoscopic activities in Crohn's disease (CD);
      however, the utility of FC levels in the postoperative setting remains to be
      determined. Using meta-analysis, we aimed to evaluate the utility of FC as a
      noninvasive marker of recurrence in patients with CD who had undergone previous
      surgical resection. METHODS: An electronic search using keywords related to CD
      and FC was performed in multiple electronic resources from 1966 to March 2014.
      The extracted data were pooled using a hierarchical summary receiver operating
      curve model. RESULTS: Ten articles met the inclusion criteria, and methodological
      quality was determined in detail for each study. The 10 studies presented FC
      levels in 613 postoperative CD patients. The pooled sensitivity and specificity
      values for assessing suspected endoscopic recurrence were 0.82 (95% confidence
      interval (CI), 0.73-0.89, 8 studies, n = 391) and 0.61 (95% CI, 0.51-0.71),
      respectively. The overall positive and negative likelihood ratios were 2.11 (95%
      CI, 1.68-2.66) and 0.29 (95% CI, 0.197-0.44), respectively. The pooled
      sensitivity and specificity values for evaluating clinical relapse were 0.59 (95%
      CI, 0.47-0.71; 3 studies, n = 183) and 0.88 (95% CI, 0.80-0.93), respectively.
      The overall positive and negative likelihood ratios were 5.10 and 0.47,
      respectively. CONCLUSIONS: As a simple and noninvasive marker, FC is useful in
      evaluating recurrence of postoperative patients with CD.

PMID- 25569740
TI  - Impact of timing and duration of thiopurine treatment on first perianal surgery
      in Crohn's disease: UK population-based study (1995-2009).
AB  - BACKGROUND: The impact of thiopurine (TP) use on perianal surgery is uncertain.
      Our aim was to determine trends in perianal surgery and the impact of timing and
      duration of TPs on the risk of first perianal surgery. METHODS: We identified a
      population-based cohort of incident cases of Crohn's disease between 1995 and
      2009. We used Kaplan-Meier analysis to determine trends in TP usage and first
      perianal surgery by era of diagnosis: era 1 (1995-2002) and era 2 (2003-2009). We
      quantified the impact of duration and timing of TPs on the risk of perianal
      surgery using a Cox regression model. RESULTS: We identified a cohort of 5235
      incident cases of Crohn's disease. The 5-year cumulative probability of first
      perianal surgery decreased from 2.7% to 1.7% between era 1 and era 2,
      respectively (P = 0.03). TP use for greater than 18 months was associated with a
      40% risk reduction for first perianal surgery (hazard ratio: 0.60, 95% confidence
      interval: 0.39-0.95) and 49% if TPs were used for 2 years or more (hazard ratio:
      0.51, 95% confidence interval: 0.32-0.99). There was no demonstrable additional
      benefit from early TP use within the first year after diagnosis (hazard ratio:
      0.85, 95% confidence interval: 0.52-1.40, P = 0.53). CONCLUSIONS: Over the past
      15 years, TP use has increased by 50%, whereas perianal surgery rates have
      decreased by 37% among UK population with Crohn's disease. Sustained use for 18
      months was associated with a reduced risk of perianal surgery by almost a half in
      the first 5 years after diagnosis.

PMID- 25569741
TI  - Characterization of expression quantitative trait loci in the human colon.
AB  - BACKGROUND: Many genetic risk loci have been identified for inflammatory bowel
      disease and colorectal cancer; however, identifying the causal genes for each
      association signal remains a challenge. Expression quantitative trait loci (eQTL)
      studies have identified common variants that induce differential gene expression
      and eQTLs can be cross-referenced with disease association signals for gene
      prioritization. However, the genetics of gene expression are highly tissue
      specific, and further eQTL datasets from primary tissues are needed. METHODS: We
      have conducted an eQTL discovery study using tissue extracted endoscopically from
      the terminal ileum and 4 colonic locations of non-inflamed bowel from 65 controls
      and patients with quiescent inflammatory bowel disease. A genome-wide cis-eQTL
      analysis was performed on >3,600,000 variants and 13,558 expressed probes.
      RESULTS: We identified 1312 independent eQTLs associated with the differential
      expression of 1222 genes in rectal mucosa. One hundred seventy-one, 211, 168, and
      102 independent eQTLs were identified in the sigmoid, descending colon, ascending
      colon, and terminal ileum, respectively. Twenty-six percent of genes with rectal
      eQTLs were novel and unique compared with 7 published eQTL datasets. Rectal eQTLs
      were significantly enriched for genes expressed in the colon. Examining 163
      inflammatory bowel disease risk loci identified 11 tag single-nucleotide
      polymorphisms that were rectal eQTLs. A colorectal cancer locus at 11q23
      contained a rectal eQTL for COLCA2, a protein implicated in colon cancer
      pathogenesis. CONCLUSIONS: This study defines a catalog of ileal and colonic
      eQTLs. Our data reaffirm the tissue specificity of eQTLs and support the notion
      that identification of functional variants in relevant tissue can be effective in
      fine-mapping genetic risk loci.

PMID- 25569742
TI  - Piroxicam treatment augments bone abnormalities in interleukin-10 knockout mice.
AB  - BACKGROUND: Osteoporosis and fractures are common complications of inflammatory
      bowel disease. The pathogenesis is multifactorial and has been partly attributed
      to intestinal inflammation. The aim of this study was to evaluate bone status and
      assess the association between bone loss and gut inflammation in an experimental
      colitis model. METHODS: Colitis was induced in interleukin-10 knockout mice (PAC
      IL-10 k.o.) by peroral administration of piroxicam for 12 days. The degree of
      colitis was assessed by clinical, macroscopic, and microscopic evaluation.
      Trabecular and cortical bone microarchitecture of tibia were determined using
      micro-computed tomography. Moreover, the serum levels of bone formation and bone
      resorption biomarkers were measured, and inflammatory protein profiling was
      performed on colons. RESULTS: PAC IL-10 k.o. mice developed severe colitis,
      characterized by hyperplasia and focal transmural inflammation, which was
      consistent with Crohn's disease-like pathology. The gut inflammation was
      accompanied by a 14% and 12% reduction in trabecular thickness relative to
      piroxicam-treated wild type and untreated wild type mice, respectively (P <
      0.001). The trabecular bone structure was also changed in PAC IL-10 k.o. mice,
      whereas no differences in cortical bone geometry were observed. The trabecular
      thickness was inversely correlated with serum levels of CTX (r = -0.93, P =
      0.006). Moreover, numerous inflammatory mediators, including RANKL and
      osteoprotegerin, were significantly increased in the colon of PAC IL-10 k.o.
      mice. CONCLUSIONS: PAC IL-10 k.o. mice develop bone loss and changed trabecular
      structure, as a result of increased bone resorption. Thus, the PAC IL-10 k.o.
      model could be a useful experimental model in preclinical research of
      inflammatory bowel disease-associated bone loss.

PMID- 25569743
TI  - Overexpression of PAK1 promotes cell survival in inflammatory bowel diseases and
      colitis-associated cancer.
AB  - BACKGROUND: Chronic gut inflammation predisposes to the development of colorectal
      cancer and increased mortality. Use of mesalamine (5-ASA) in the treatment of
      ulcerative colitis modulates the risk of neoplastic progression. p21 activated
      kinase 1 (PAK1) mediates 5-ASA activity by orchestrating MAPK signaling, Wnt-beta
      catenin pathway, and cell adhesion; all implicated in the colon carcinogenesis.
      We evaluated the role of PAK1 in IBD and in colitis-associated cancer (CAC).
      METHODS AND RESULTS: PAK1 expression was scored by immunohistochemistry in human
      samples from IBD, CAC, and in normal mucosa. Compared with controls, a higher
      PAK1 expression was detected in IBD which further increased in CAC. The
      consequence of PAK1 overexpression was investigated using normal diploid colon
      epithelial cells (HCEC-1CT), which showed higher proliferation and decreased
      apoptosis on overexpression of PAK1. Analysis of IBD and CAC samples showed
      activation of AKT (p-AKT). However, mTOR pathway was activated in IBD but not in
      CAC. Treatment of cells with specific inhibitors (PD98059/LY294002/rapamycin) of
      growth signaling pathways (MEK/PI3K/mTOR) demonstrated that in HCEC-1CT, PAK1
      expression is regulated by MEK, PI3K, and mTOR. In colorectal cancer cell lines,
      PAK1, and beta-catenin expression correlated and inhibition of PAK1 and addition
      of 5-ASA elicited similar molecular affects by reducing ERK and AKT activation.
      Moreover, 5-ASA disrupted PAK1 interaction and colocalization with beta-catenin.
      CONCLUSIONS: Our data indicate that (1) PAK1 is upregulated in IBD and CAC (2)
      PAK1 overexpression is associated with activation of PI3K-AKT/mTOR prosurvival
      pathways in IBD.

PMID- 25569744
TI  - Calcified parenchymal central nervous system cysticercosis and clinical outcomes
      in epilepsy.
AB  - OBJECTIVE: This study aimed to compare clinical outcomes including seizure
      frequency and psychiatric symptoms between patients with epilepsy with
      neuroimaging evidence of past brain parenchymal neurocysticercosis infection,
      patients with other structural brain lesions, and patients without structural
      neuroimaging abnormalities. MATERIAL AND METHODS: The study included
      retrospective cross-sectional analysis of all patients treated for epilepsy in a
      community-based adult neurology clinic during a three-month period. RESULTS: A
      total of 160 patients were included in the analysis, including 63 with
      neuroimaging findings consistent with past parenchymal neurocysticercosis
      infection, 55 with structurally normal brain neuroimaging studies, and 42 with
      other structural brain lesions. No significant differences were detected between
      groups for either seizure freedom (46.03%, 50.91%, and 47.62%, respectively;
      p=0.944) or mean seizure frequency per month (mean=2.50, S.D.=8.1; mean=4.83,
      S.D.=17.64; mean=8.55, S.D.=27.31, respectively; p=0.267). Self-reported
      depressive symptoms were more prevalent in those with parenchymal
      neurocysticercosis than in the other groups (p=0.003). No significant differences
      were detected for prevalence of self-reported anxiety or psychotic symptoms.
      CONCLUSIONS: Calcified parenchymal neurocysticercosis results in refractory
      epilepsy about as often as other structural brain lesions. Depressive symptoms
      may be more common among those with epilepsy and calcified parenchymal
      neurocysticercosis; consequently, screening for depression may be indicated in
      this population.

PMID- 25569745
TI  - Quality of life in psychogenic nonepileptic seizures and epilepsy: the role of
      somatization and alexithymia.
AB  - It is clear that many individuals with psychogenic nonepileptic seizures (PNESs)
      often present with poorer quality of life compared with those with epileptic
      seizures (ESs). However, the mechanisms linking seizure diagnosis to quality-of
      life outcomes are much less clear. Alexithymia and somatization are emotional
      markers of psychological functioning that may explain these differences in
      quality of life. In the current study, patients from an epilepsy monitoring unit
      with vEEG-confirmed diagnosis of PNESs or ESs were compared on measures of
      alexithymia, somatization, quality of life, and a variety of demographic and
      medical variables. Two models using alexithymia and somatization individually as
      mediators of the relations between diagnosis and quality of life were tested.
      Results indicated that patients with PNESs had significantly poorer quality of
      life compared with those with ESs. Alexithymia was associated with poor quality
      of life in both groups but did not differentiate between diagnostic groups.
      Further, alexithymia did not mediate the relationship between diagnosis and
      quality of life. Somatization was associated with poor quality of life, and
      patients with PNESs reported greater somatization compared with patients with
      ESs. Somatization also significantly mediated the relationship between diagnosis
      and quality of life. In conclusion, somatization may be one mechanism affecting
      poor quality of life among patients with PNESs compared with ESs and should be a
      target of comprehensive treatments for PNESs. Alexithymia proved to be an
      important factor impacting quality of life in both groups and should also be
      targeted in treatment for patients with PNESs and patients with ESs. 

PMID- 25569746
TI  - A novel inherited SCN1A mutation associated with different neuropsychological
      phenotypes: is there a common core deficit?
AB  - We report a three-generation, clinically heterogeneous family in which we
      identify a novel inherited splicing mutation of the SCN1A gene. Thirteen subjects
      were submitted to genetic analysis, clinical and instrumental examination, and
      neuropsychological assessment. In eight subjects, a heterozygous c.2946+5G>A
      donor splice site alteration in the SCN1A gene was found. Half of them had never
      had a seizure and showed normal EEG and cognitive profile, whereas the other half
      had a history of seizures and variable neuropsychological impairments ranging
      from moderate cognitive disabilities to mild visual-motor impairments. Different
      clinical phenotypes were identified, including generalized epilepsy with febrile
      seizure plus (GEFS+), Dravet syndrome, and partial epilepsy with febrile seizure
      plus (PEFS+). Remarkable clinical heterogeneity can be found among family members
      carrying the same SCN1A gene mutation. Variable involvement of visual-motor
      abilities might represent a neuropsychological feature which needs to be further
      explored in other familial cases. 

PMID- 25569747
TI  - An ecological framework for sexual minority women's health: factors associated
      with greater body mass.
AB  - In recent years, many studies have focused on the body of sexual minority women,
      particularly emphasizing their larger size. These studies rarely offer
      theoretically based explanations for the increased weight, nor study the
      potential consequences (or lack thereof) of being heavier. This article provides
      a brief overview of the multitude of factors that might cause or contribute to
      larger size of sexual minority women, using an ecological framework that
      elucidates upstream social determinants of health as well as individual risk
      factors. This model is infused with a minority stress model, which hypothesizes
      excess strain resulting from the stigma associated with oppressed minority
      identities such as woman, lesbian, bisexual, woman of color, and others. We argue
      that lack of attention to the upstream social determinants of health may result
      in individual-level victim blaming and interventions that do not address the root
      causes of minority stress or increased weight. 

PMID- 25569748
TI  - A new z-axis resonant micro-accelerometer based on electrostatic stiffness.
AB  - Presented in the paper is the design, the simulation, the fabrication and the
      experiment of a new z-axis resonant accelerometer based on the electrostatic
      stiffness. The new z-axis resonant micro-accelerometer, which consists of a
      torsional accelerometer and two plane resonators, decouples the sensing movement
      of the accelerometer from the oscillation of the plane resonators by
      electrostatic stiffness, which will improve the performance. The new structure
      and the sensitive theory of the acceleration are illuminated, and the equation of
      the scale factor is deduced under ideal conditions firstly. The Ansys simulation
      is implemented to verify the basic principle of the torsional accelerometer and
      the plane resonator individually. The structure simulation results prove that the
      effective frequency of the torsional accelerometer and the plane resonator are
      0.66 kHz and 13.3 kHz, respectively. Then, the new structure is fabricated by the
      standard three-mask deep dry silicon on glass (DDSOG) process and encapsulated by
      parallel seam welding. Finally, the detecting and control circuits are designed
      to achieve the closed-loop self-oscillation, to trace the natural frequency of
      resonator and to measure the system frequency. Experimental results show that the
      new z-axis resonant accelerometer has a scale factor of 31.65 Hz/g, a bias
      stability of 727 ug and a dynamic range of over 10 g, which proves that the new z
      axis resonant micro-accelerometer is practicable. 

PMID- 25569749
TI  - Direct fusion of geostationary meteorological satellite visible and infrared
      images based on thermal physical properties.
AB  - This study investigated a novel method of fusing visible (VIS) and infrared (IR)
      images with the major objective of obtaining higher-resolution IR images. Most
      existing image fusion methods focus only on visual performance and many fail to
      consider the thermal physical properties of the IR images, leading to spectral
      distortion in the fused image. In this study, we use the IR thermal physical
      property to correct the VIS image directly. Specifically, the Stefan-Boltzmann
      Law is used as a strong constraint to modulate the VIS image, such that the fused
      result shows a similar level of regional thermal energy as the original IR image,
      while preserving the high-resolution structural features from the VIS image. This
      method is an improvement over our previous study, which required VIS-IR multi
      wavelet fusion before the same correction method was applied. The results of
      experiments show that applying this correction to the VIS image directly without
      multi-resolution analysis (MRA) processing achieves similar results, but is
      considerably more computationally efficient, thereby providing a new perspective
      on VIS and IR image fusion. 

PMID- 25569750
TI  - Fusion of WiFi, smartphone sensors and landmarks using the Kalman filter for
      indoor localization.
AB  - Location-based services (LBS) have attracted a great deal of attention recently.
      Outdoor localization can be solved by the GPS technique, but how to accurately
      and efficiently localize pedestrians in indoor environments is still a
      challenging problem. Recent techniques based on WiFi or pedestrian dead reckoning
      (PDR) have several limiting problems, such as the variation of WiFi signals and
      the drift of PDR. An auxiliary tool for indoor localization is landmarks, which
      can be easily identified based on specific sensor patterns in the environment,
      and this will be exploited in our proposed approach. In this work, we propose a
      sensor fusion framework for combining WiFi, PDR and landmarks. Since the whole
      system is running on a smartphone, which is resource limited, we formulate the
      sensor fusion problem in a linear perspective, then a Kalman filter is applied
      instead of a particle filter, which is widely used in the literature.
      Furthermore, novel techniques to enhance the accuracy of individual approaches
      are adopted. In the experiments, an Android app is developed for real-time indoor
      localization and navigation. A comparison has been made between our proposed
      approach and individual approaches. The results show significant improvement
      using our proposed framework. Our proposed system can provide an average
      localization accuracy of 1 m. 

PMID- 25569751
TI  - Modeling and development of INS-aided PLLs in a GNSS/INS deeply-coupled hardware
      prototype for dynamic applications.
AB  - A GNSS/INS deeply-coupled system can improve the satellite signals tracking
      performance by INS aiding tracking loops under dynamics. However, there was no
      literature available on the complete modeling of the INS branch in the INS-aided
      tracking loop, which caused the lack of a theoretical tool to guide the
      selections of inertial sensors, parameter optimization and quantitative analysis
      of INS-aided PLLs. This paper makes an effort on the INS branch in modeling and
      parameter optimization of phase-locked loops (PLLs) based on the scalar-based
      GNSS/INS deeply-coupled system. It establishes the transfer function between all
      known error sources and the PLL tracking error, which can be used to
      quantitatively evaluate the candidate inertial measurement unit (IMU) affecting
      the carrier phase tracking error. Based on that, a steady-state error model is
      proposed to design INS-aided PLLs and to analyze their tracking performance.
      Based on the modeling and error analysis, an integrated deeply-coupled hardware
      prototype is developed, with the optimization of the aiding information. Finally,
      the performance of the INS-aided PLLs designed based on the proposed steady-state
      error model is evaluated through the simulation and road tests of the hardware
      prototype. 

PMID- 25569753
TI  - Application of remote sensors in mapping rice area and forecasting its
      production: a review.
AB  - Rice is one of the staple foods for more than three billion people worldwide.
      Rice paddies accounted for approximately 11.5% of the World's arable land area
      during 2012. Rice provided ~19% of the global dietary energy in recent times and
      its annual average consumption per capita was ~65 kg during 2010-2011. Therefore,
      rice area mapping and forecasting its production is important for food security,
      where demands often exceed production due to an ever increasing population.
      Timely and accurate estimation of rice areas and forecasting its production can
      provide invaluable information for governments, planners, and decision makers in
      formulating policies in regard to import/export in the event of shortfall and/or
      surplus. The aim of this paper was to review the applicability of the remote
      sensing-based imagery for rice area mapping and forecasting its production.
      Recent advances on the resolutions (i.e., spectral, spatial, radiometric, and
      temporal) and availability of remote sensing imagery have allowed us timely
      collection of information on the growth and development stages of the rice crop.
      For elaborative understanding of the application of remote sensing sensors,
      following issues were described: the rice area mapping and forecasting its
      production using optical and microwave imagery, synergy between remote sensing
      based methods and other developments, and their implications as an operational
      one. The overview of the studies to date indicated that remote sensing-based
      methods using optical and microwave imagery found to be encouraging. However,
      there were having some limitations, such as: (i) optical remote sensing imagery
      had relatively low spatial resolution led to inaccurate estimation of rice areas;
      and (ii) radar imagery would suffer from speckles, which potentially would
      degrade the quality of the images; and also the brightness of the backscatters
      were sensitive to the interacting surface. In addition, most of the methods used
      in forecasting rice yield were empirical in nature, so thus it would require
      further calibration and validation prior to implement over other geographical
      locations. 

PMID- 25569752
TI  - Creating diversified response profiles from a single quenchometric sensor element
      by using phase-resolved luminescence.
AB  - We report a new strategy for generating a continuum of response profiles from a
      single luminescence-based sensor element by using phase-resolved detection. This
      strategy yields reliable responses that depend in a predictable manner on changes
      in the luminescent reporter lifetime in the presence of the target analyte, the
      excitation modulation frequency, and the detector (lock-in amplifier) phase
      angle. In the traditional steady-state mode, the sensor that we evaluate exhibits
      a linear, positive going response to changes in the target analyte concentration.
      Under phase-resolved conditions the analyte-dependent response profiles: (i) can
      become highly non-linear; (ii) yield negative going responses; (iii) can be
      biphasic; and (iv) can exhibit super sensitivity (e.g., sensitivities up to 300
      fold greater in comparison to steady-state conditions). 

PMID- 25569754
TI  - Automatic laser glare suppression in electro-optical sensors.
AB  - Progress in laser technology has led to very compact but nevertheless powerful
      laser sources. In the visible and near infrared spectral region, lasers of any
      wavelength can be purchased. Continuous wave laser sources pose an especially
      serious threat to the human eye and electro-optical sensors due to their high
      proliferation and easy availability. The manifold of available wavelengths cannot
      be covered by conventional safety measures like absorption or interference
      filters. We present a protection concept for electro-optical sensors to suppress
      dazzling in the visible spectral region. The key element of the concept is the
      use of a digital micromirror device (DMD) in combination with wavelength
      multiplexing. This approach allows selective spectral filtering in defined
      regions of interest in the scene. The system offers the possibility of automatic
      attenuation of dazzling laser radiation. 

PMID- 25569755
TI  - Weighted geometric dilution of precision calculations with matrix multiplication.
AB  - To enhance the performance of location estimation in wireless positioning
      systems, the geometric dilution of precision (GDOP) is widely used as a criterion
      for selecting measurement units. Since GDOP represents the geometric effect on
      the relationship between measurement error and positioning determination error,
      the smallest GDOP of the measurement unit subset is usually chosen for
      positioning. The conventional GDOP calculation using matrix inversion method
      requires many operations. Because more and more measurement units can be chosen
      nowadays, an efficient calculation should be designed to decrease the complexity.
      Since the performance of each measurement unit is different, the weighted GDOP
      (WGDOP), instead of GDOP, is used to select the measurement units to improve the
      accuracy of location. To calculate WGDOP effectively and efficiently, the closed
      form solution for WGDOP calculation is proposed when more than four measurements
      are available. In this paper, an efficient WGDOP calculation method applying
      matrix multiplication that is easy for hardware implementation is proposed. In
      addition, the proposed method can be used when more than exactly four
      measurements are available. Even when using all-in-view method for positioning,
      the proposed method still can reduce the computational overhead. The proposed
      WGDOP methods with less computation are compatible with global positioning system
      (GPS), wireless sensor networks (WSN) and cellular communication systems. 

PMID- 25569756
TI  - Characterization of piezoresistive PEDOT:PSS pressure sensors with inter
      digitated and cross-point electrode structures.
AB  - The piezoresistive characteristics of poly(3,4
      ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) pressure sensors with
      inter-digitated (IDE) and cross-point electrode (CPE) structures have been
      investigated. A small variation of the resistance of the pressure sensors with
      IDE without bottom indium-tin-oxide (b-ITO) film and with CPE structures was
      observed owing to the single carrier-conducting pathway. For the IDE pressure
      sensors with b-ITO, the piezoresistive characteristics at low and high pressure
      were similar to those of the pressure sensors with IDE without b-ITO and with CPE
      structures, respectively, leading to increased piezoresistive pressure
      sensitivity as the PEDOT:PSS film thickness decreased. A maximum sensitivity of
      more than 42 kOmega/Pa was achieved. When the normal pressure was applied, the
      increased number of conducting points or the reduced distance between the PEDOT
      oligomers within the PEDOT:PSS film resulted in a decrease of the resistance. The
      piezoresistive pressure sensors with a single carrier-conducting pathway, i.e.,
      IDE without b-ITO and CPE structures, exhibited a small relaxation time and a
      superior reversible operation, which can be advantageous for fast piezoresistive
      response applications. 

PMID- 25569757
TI  - A multi-channel, flex-rigid ECoG microelectrode array for visual cortical
      interfacing.
AB  - High-density electrocortical (ECoG) microelectrode arrays are promising signal
      acquisition platforms for brain-computer interfaces envisioned, e.g., as high
      performance communication solutions for paralyzed persons. We propose a multi
      channel microelectrode array capable of recording ECoG field potentials with high
      spatial resolution. The proposed array is of a 150 mm2 total recording area; it
      has 124 circular electrodes (100, 300 and 500 um in diameter) situated on the
      edges of concentric hexagons (min. 0.8 mm interdistance) and a skull-facing
      reference electrode (2.5 mm2 surface area). The array is processed as a free
      standing device to enable monolithic integration of a rigid interposer, designed
      for soldering of fine-pitch SMD-connectors on a minimal assembly area.
      Electrochemical characterization revealed distinct impedance spectral bands for
      the 100, 300 and 500 um-type electrodes, and for the array's own reference.
      Epidural recordings from the primary visual cortex (V1) of an awake Rhesus
      macaque showed natural electrophysiological signals and clear responses to
      standard visual stimulation. The ECoG electrodes of larger surface area recorded
      signals with greater spectral power in the gamma band, while the skull-facing
      reference electrode provided higher average gamma power spectral density
      (gammaPSD) than the common average referencing technique. 

PMID- 25569760
TI  - Fast image restoration for spatially varying defocus blur of imaging sensor.
AB  - This paper presents a fast adaptive image restoration method for removing
      spatially varying out-of-focus blur of a general imaging sensor. After estimating
      the parameters of space-variant point-spread-function (PSF) using the derivative
      in each uniformly blurred region, the proposed method performs spatially adaptive
      image restoration by selecting the optimal restoration filter according to the
      estimated blur parameters. Each restoration filter is implemented in the form of
      a combination of multiple FIR filters, which guarantees the fast image
      restoration without the need of iterative or recursive processing. Experimental
      results show that the proposed method outperforms existing space-invariant
      restoration methods in the sense of both objective and subjective performance
      measures. The proposed algorithm can be employed to a wide area of image
      restoration applications, such as mobile imaging devices, robot vision, and
      satellite image processing. 

PMID- 25569758
TI  - Hyper, a hydrogen peroxide sensor, indicates the sensitivity of the Arabidopsis
      root elongation zone to aluminum treatment.
AB  - Emerging evidence indicates that some reactive oxygen species (ROS), such as the
      superoxide anion radical and hydrogen peroxide (H2O2), are central regulators of
      plant responses to biotic and abiotic stresses. Thus, the cellular levels of ROS
      are thought to be tightly regulated by an efficient and elaborate pro- and
      antioxidant system that modulates the production and scavenging of ROS. Until
      recently, studies of ROS in plant cells have been limited to biochemical assays
      and the use of fluorescent probes; however, the irreversible oxidation of these
      fluorescent probes makes it impossible to visualize dynamic changes in ROS
      levels. In this work, we describe the use of Hyper, a recently developed live
      cell probe for H2O2 measurements in living cells, to monitor oxidative stress in
      Arabidopsis roots subjected to aluminum treatment. Hyper consists of a circularly
      permuted YFP (cpYFP) inserted into the regulatory domain of the Escherichia coli
      hydrogen peroxide-binding protein (OxyR), and is a H2O2-specific ratiometric, and
      therefore quantitative, probe that can be expressed in plant and animal cells.
      Now we demonstrate that H2O2 levels drop sharply in the elongation zone of roots
      treated with aluminum. This response could contribute to root growth arrest and
      provides evidence that H2O2 is involved in early Al sensing. 

PMID- 25569759
TI  - Carbon fiber ultramicrodic electrode electrodeposited with over-oxidized
      polypyrrole for amperometric detection of vesicular exocytosis from
      pheochromocytoma cell.
AB  - Vesicular exocytosis is ubiquitous, but it is difficult to detect within the
      cells' communication mechanism. For this purpose, a 2 um ultramicrodic carbon
      fiber electrode was fabricated in this work based on electrodeposition with over
      oxidized polypyrrole nanoparticle (PPyox-CFE), which was applied successfully for
      real-time monitoring of quantal exocytosis from individual pheochromocytoma
      (PC12) cells. PPyox-CFE was evaluated by dopamine (DA) solutions through cyclic
      voltammetry and amperometry electrochemical methods, and results revealed that
      PPyox-CFE improved the detection limit of DA. In particular, the sensitivity of
      DA was improved to 24.55 uA.uM(-1).um(-2) using the PPyox-CFE. The ultramicrodic
      electrode combined with the patch-clamp system was used to detect vesicular
      exocytosis of DA from individual PC12 cells with 60 mM K+ stimulation. A total of
      287 spikes released from 7 PC12 cells were statistically analyzed. The current
      amplitude (Imax) and the released charge (Q) of the amperometric spikes from the
      DA release by a stimulated PC12 cell is 45.1 +/- 12.5 pA and 0.18 +/- 0.04 pC,
      respectively. Furthermore, on average ~562,000 molecules were released in each
      vesicular exocytosis. PPyox-CFE, with its capability of detecting vesicular
      exocytosis, has potential application in neuron communication research.

PMID- 25569761
TI  - Electronic-nose applications for fruit identification, ripeness and quality
      grading.
AB  - Fruits produce a wide range of volatile organic compounds that impart their
      characteristically distinct aromas and contribute to unique flavor
      characteristics. Fruit aroma and flavor characteristics are of key importance in
      determining consumer acceptance in commercial fruit markets based on individual
      preference. Fruit producers, suppliers and retailers traditionally utilize and
      rely on human testers or panels to evaluate fruit quality and aroma characters
      for assessing fruit salability in fresh markets. We explore the current and
      potential utilization of electronic-nose devices (with specialized sensor
      arrays), instruments that are very effective in discriminating complex mixtures
      of fruit volatiles, as new effective tools for more efficient fruit aroma
      analyses to replace conventional expensive methods used in fruit aroma
      assessments. We review the chemical nature of fruit volatiles during all stages
      of the agro-fruit production process, describe some of the more important
      applications that electronic nose (e-nose) technologies have provided for fruit
      aroma characterizations, and summarize recent research providing e-nose data on
      the effectiveness of these specialized gas-sensing instruments for fruit
      identifications, cultivar discriminations, ripeness assessments and fruit grading
      for assuring fruit quality in commercial markets. 

PMID- 25569762
TI  - The "5Rs of Reorganization": A Case Report on Service Delivery Reorganization
      within a Pediatric Rehabilitation Organization.
AB  - AIMS: Pediatric rehabilitation centers constantly reorganize services to
      accommodate changes in funding, client needs, evidence-based practices,
      accountability requirements, theoretical models, and values. However, there are
      few service delivery models or descriptions of how organizations plan for change
      to guide organizations through this complex task. METHODS: This case report
      presents the "5Rs of Reorganization," a novel process for planning service
      delivery reorganization projects in pediatric rehabilitation centers. The 5Rs
      include: 1. Recognize the need for change, 2. Reallocate resources for project
      management, 3. Review the reality of clients, service delivery, and the
      community, 4. Reconstruct reality, and 5. Report results. RESULTS: The
      implementation and outcomes of the "5Rs of Reorganization" process are described
      for one pediatric rehabilitation center to illustrate how use of this process led
      to effective service delivery reorganization planning. The resulting multi
      component customized service delivery plan reflects high levels of stakeholder
      involvement. CONCLUSIONS: Principles of project management can be applied to
      support service delivery reorganization planning within pediatric rehabilitation
      centers using the "5Rs of Reorganization." Strong communication throughout the
      planning phase is key to developing and sharing a plan for service delivery
      reorganization. Communication can be supported through use of the 5R process.

PMID- 25569764
TI  - The smarter, the stronger: intelligence level correlates with brain resilience to
      systematic insults.
AB  - Neuroimaging evidences posit human intelligence as tightly coupled with several
      structural and functional brain properties, also suggesting its potential
      protective role against aging and neurodegenerative conditions. However, whether
      higher order cognition might in fact lead to a more resilient brain has not been
      quantitatively demonstrated yet. Here we document a relationship between
      individual intelligence quotient (IQ) and brain resilience to targeted and random
      attacks, as measured through resting-state fMRI graph-theoretical analysis in 102
      healthy individuals. In this modeling context, enhanced brain robustness to
      targeted attacks (TA) in individuals with higher IQ is supported by an increased
      distributed processing capacity despite the systematic loss of the most important
      node(s) of the system. Moreover, brain resilience in individuals with higher IQ
      is supported by a set of neocortical regions mainly belonging to language and
      memory processing network(s), whereas regions related to emotional processing are
      mostly responsible for lower IQ individuals. Results suggest intelligence level
      among the predictors of post-lesional or neurodegenerative recovery, also
      promoting the evolutionary role of higher order cognition, and simultaneously
      suggesting a new framework for brain stimulation interventions aimed at
      counteract brain deterioration over time. 

PMID- 25569767
TI  - Why Interdisciplinary Teams Ten Years Later?

PMID- 25569763
TI  - Ventromedial prefrontal cortex damage alters resting blood flow to the bed
      nucleus of stria terminalis.
AB  - The ventromedial prefrontal cortex (vmPFC) plays a key role in modulating
      emotional responses, yet the precise neural mechanisms underlying this function
      remain unclear. vmPFC interacts with a number of subcortical structures involved
      in affective processing, including the amygdala, hypothalamus, periaqueductal
      gray, ventral striatum, and bed nucleus of stria terminalis (BNST). While a
      previous study of non-human primates shows that vmPFC lesions reduce BNST
      activity and anxious behavior, no such causal evidence exists in humans. In this
      study, we used a novel application of magnetic resonance imaging (MRI) in
      neurosurgical patients with focal, bilateral vmPFC damage to determine whether
      vmPFC is indeed critical for modulating BNST function in humans. Relative to
      neurologically healthy subjects, who exhibited robust rest-state functional
      connectivity between vmPFC and BNST, the vmPFC lesion patients had significantly
      lower resting-state perfusion of the right BNST. No such perfusion differences
      were observed for the amygdala, striatum, hypothalamus, or periaqueductal gray.
      This study thus provides unique data on the relationship between vmPFC and BNST,
      suggesting that vmPFC serves to promote BNST activity in humans. This finding is
      relevant for neural circuitry models of mood and anxiety disorders. 

PMID- 25569768
TI  - Production of biobutanol from acid-pretreated corncob using Clostridium
      beijerinckii TISTR 1461: Process optimization studies.
AB  - Corncob is a potential feedstock in Thailand that can be used for fermentable
      sugar production through dilute sulfuric acid pretreatment and enzymatic
      hydrolysis. To recover high amounts of monomeric sugars from corncob, the
      sulfuric pretreatment conditions were optimized by using response surface
      methodology with three independent variables: sulfuric acid concentration,
      temperature, and time. The highest response of total sugars, 48.84 g/L, was found
      at 122.78 degrees C, 4.65 min, and 2.82% (v/v) H2SO4. With these conditions,
      total sugars from the confirmation experiment were 46.29 g/L, with 5.51% error
      from the predicted value. The hydrolysate was used as a substrate for acetone
      butanol-ethanol fermentation to evaluate its potential for microbial growth. The
      simultaneous saccharification and fermentation (SSF) showed that C. beijerinckii
      TISTR 1461 can generate acetone-butanol-ethanol products at 11.64 g/L (5.29 g/L
      acetone, 6.26 g/L butanol, and 0.09 g/L ethanol) instantly using sugars from the
      hydrolysed corncob with Novozymes 50013 cellulase enzyme without an overliming
      process.

PMID- 25569769
TI  - Six people in US die each day from alcohol poisoning, CDC reports.

PMID- 25569765
TI  - Primary adherence to controller medications for asthma is poor.
AB  - RATIONALE: Few previous studies have evaluated primary adherence (whether a new
      prescription is filled within 30 d) to controller medications in individuals with
      persistent asthma. OBJECTIVE: To compare adherence to the major controller
      medication regimens for asthma. METHODS: This was a retrospective cohort study of
      enrollees from five large health plans. We used electronic medical data on
      patients of all ages with asthma who had experienced an asthma-related
      exacerbation in the prior 12 months. We studied adherence measures including
      proportion of days covered and primary adherence (first prescription filled
      within 30 d). MEASUREMENTS AND MAIN RESULTS: Our population included 69,652
      subjects who had probable persistent asthma and were prescribed inhaled
      corticosteroids (ICSs), leukotriene antagonists (LTRAs), or ICS/long-acting beta
      agonists (ICS/LABAs). The mean age was 37 years and 58% were female. We found
      that 14-20% of subjects who were prescribed controller medicines for the first
      time did not fill their prescriptions. The mean proportion of days covered was
      19% for ICS, 30% for LTRA, and 25% for ICS/LABA over 12 months. Using
      multivariate logistic regression, subjects prescribed LTRA were less likely to be
      primary adherent than subjects prescribed ICS (odds ratio, 0.82; 95% confidence
      interval, 0.74-0.92) or ICS/LABA (odds ratio, 0.88; 95% confidence interval, 0.80
      0.97). Black and Latino patients were less likely to fill the prescription
      compared with white patients. CONCLUSIONS: Adherence to controller medications
      for asthma is poor. In this insured population, primary adherence to ICSs was
      better than to LTRAs and ICS/LABAs. Adherence as measured by proportion of days
      covered was better for LTRAs and ICS/LABAs than for ICSs.

PMID- 25569770
TI  - Nature of aryl-tyrosine interactions contribute to beta-hairpin scaffold
      stability: NMR evidence for alternate ring geometry.
AB  - The specific contribution of the acidic-aromatic beta-sheet favouring amino acid
      tyrosine to the stability of short octapeptide beta-hairpin structures is
      presented here. Solution NMR analysis in near-apolar environments suggests the
      energetically favourable mode of interaction to be T-shaped face-to-edge (FtE)
      and that a Trp-Tyr interacting pair is the most stabilizing. Alternate aryl
      geometries also exist in solution, which readily equilibrate between a preferred
      pi...pi conformation to an aromatic-amide conformation, without any change in the
      backbone structure. While the phenolic ring is readily accommodated at the "edge"
      of FtE aryl interactions, it exhibits an overall lowered contribution to scaffold
      stability in the "face" orientation. Such differential tyrosine interactions are
      key to its dual nature in proteins.

PMID- 25569771
TI  - House dust mites induce proliferation of severe asthmatic smooth muscle cells via
      an epithelium-dependent pathway.
AB  - RATIONALE: Asthma is a frequent airway disease, and asthma control determinants
      have been associated with indoor allergen sensitization. The most frequent
      allergens are house dust mites (HDM), which act in vivo on the bronchial
      epithelial layer. Severe asthma has also been associated with bronchial
      remodeling and more specifically with increased mass of bronchial smooth muscle
      (BSM). However, the relationship between HDM stimulation of the bronchial
      epithelial layer and BSM remodeling is unknown. OBJECTIVES: To evaluate whether
      epithelial stimulation with HDM induces BSM cell proliferation in subjects with
      severe asthma. METHODS: A total of 22 subjects with severe asthma and 27 subjects
      with no asthma were recruited. We have developed an in vitro culture model
      combining an epithelium layer in air-liquid interface (ALI) interacting with BSM.
      We assessed BSM proliferation using BrdU incorporation. We explored the role of
      epithelium-derived mediators using reverse-transcriptase polymerase chain
      reaction (RT-PCR) and ELISA in vitro and in vivo. Finally, leukotrienes receptor
      expression was assessed in vitro by flow cytometry and RT-PCR and ex vivo by
      laser microdissection and RT-PCR. MEASUREMENTS AND MAIN RESULTS: We found that
      epithelial stimulation by HDM selectively increased the proliferation of
      asthmatic BSM cells and not that of nonasthmatic cells. The mechanism involved
      epithelial protease-activated receptor-2-dependent production of leukotrienes C4
      associated with an overexpression of leukotrienes receptor CysLTR1 by asthmatic
      BSM cells in vitro and ex vivo. CONCLUSIONS: This work demonstrates the selective
      role of HDM on BSM remodeling in patients with severe asthma and points out
      different therapeutic targets at epithelial and smooth muscle levels.

PMID- 25569772
TI  - Modulation of elementary calcium release mediates a transition from puffs to
      waves in an IP3R cluster model.
AB  - The oscillating concentration of intracellular calcium is one of the most
      important examples for collective dynamics in cell biology. Localized releases of
      calcium through clusters of inositol 1,4,5-trisphosphate receptor channels
      constitute elementary signals called calcium puffs. Coupling by diffusing calcium
      leads to global releases and waves, but the exact mechanism of inter-cluster
      coupling and triggering of waves is unknown. To elucidate the relation of puffs
      and waves, we here model a cluster of IP3R channels using a gating scheme with
      variable non-equilibrium IP3 binding. Hybrid stochastic and deterministic
      simulations show that puffs are not stereotyped events of constant duration but
      are sensitive to stimulation strength and residual calcium. For increasing IP3
      concentration, the release events become modulated at a timescale of minutes,
      with repetitive wave-like releases interspersed with several puffs. This
      modulation is consistent with experimental observations we present, including
      refractoriness and increase of puff frequency during the inter-wave interval. Our
      results suggest that waves are established by a random but time-modulated
      appearance of sustained release events, which have a high potential to trigger
      and synchronize activity throughout the cell. 

PMID- 25569773
TI  - Protein poly(ADP-ribosyl)ation regulates arabidopsis immune gene expression and
      defense responses.
AB  - Perception of microbe-associated molecular patterns (MAMPs) elicits
      transcriptional reprogramming in hosts and activates defense to pathogen attacks.
      The molecular mechanisms underlying plant pattern-triggered immunity remain
      elusive. A genetic screen identified Arabidopsis poly(ADP-ribose) glycohydrolase
      1 (atparg1) mutant with elevated immune gene expression upon multiple MAMP and
      pathogen treatments. Poly(ADP-ribose) glycohydrolase (PARG) is predicted to
      remove poly(ADP-ribose) polymers on acceptor proteins modified by poly(ADP
      ribose) polymerases (PARPs) with three PARPs and two PARGs in Arabidopsis genome.
      AtPARP1 and AtPARP2 possess poly(ADP-ribose) polymerase activity, and the
      activity of AtPARP2 was enhanced by MAMP treatment. AtPARG1, but not AtPARG2,
      carries glycohydrolase activity in vivo and in vitro. Importantly, mutation
      (G450R) in atparg1 blocks its activity and the corresponding residue is highly
      conserved and essential for human HsPARG activity. Consistently, mutant
      atparp1atparp2 plants exhibited compromised immune gene activation and enhanced
      susceptibility to pathogen infections. Our study indicates that protein poly(ADP
      ribosyl)ation plays critical roles in plant immune gene expression and defense to
      pathogen attacks. 

PMID- 25569774
TI  - An AP endonuclease functions in active DNA demethylation and gene imprinting in
      Arabidopsis [corrected].
AB  - Active DNA demethylation in plants occurs through base excision repair, beginning
      with removal of methylated cytosine by the ROS1/DME subfamily of 5-methylcytosine
      DNA glycosylases. Active DNA demethylation in animals requires the DNA
      glycosylase TDG or MBD4, which functions after oxidation or deamination of 5
      methylcytosine, respectively. However, little is known about the steps following
      DNA glycosylase action in the active DNA demethylation pathways in plants and
      animals. We show here that the Arabidopsis APE1L protein has
      apurinic/apyrimidinic endonuclease activities and functions downstream of ROS1
      and DME. APE1L and ROS1 interact in vitro and co-localize in vivo. Whole genome
      bisulfite sequencing of ape1l mutant plants revealed widespread alterations in
      DNA methylation. We show that the ape1l/zdp double mutant displays embryonic
      lethality. Notably, the ape1l+/-zdp-/- mutant shows a maternal-effect lethality
      phenotype. APE1L and the DNA phosphatase ZDP are required for FWA and MEA gene
      imprinting in the endosperm and are important for seed development. Thus, APE1L
      is a new component of the active DNA demethylation pathway and, together with
      ZDP, regulates gene imprinting in Arabidopsis. 

PMID- 25569775
TI  - Buruli ulcer in South Western Nigeria: a retrospective cohort study of patients
      treated in Benin.
AB  - Nigeria is known to be endemic to Buruli ulcer, but epidemiological data are
      remarkably rare. Here, we present a large cohort of 127 PCR-confirmed M. ulcerans
      infection patients coming from Nigeria and treated in a neighbouring country,
      Benin. Severe lesions and delay of consultation are factors that should encourage
      establishment of a treatment centre in South Western Nigeria. 

PMID- 25569777
TI  - Detection of vulnerable atherosclerosis plaques with a dual-modal single-photon
      emission computed tomography/magnetic resonance imaging probe targeting apoptotic
      macrophages.
AB  - Atherosclerosis (AS), especially the vulnerable AS plaque rupture-induced acute
      obstructive vascular disease, is a leading cause of death. Accordingly, there is
      a need for an effective method to draw accurate predictions about AS progression
      and plaque vulnerability. Herein we report on an approach to constructing a
      hybrid nanoparticle system using a single-photon-emission computed tomography
      (SPECT)/magnetic resonance imaging (MRI) multimodal probe, aiming for a
      comprehensive evaluation of AS progression by achieving high sensitivity along
      with high resolution. Ultrasmall superparamagnetic iron oxide (USPIO) was covered
      by aminated poly(ethylene glycol) (PEG) and carboxylated PEG simultaneously and
      then functionalized with diethylenetriaminepentacetate acid for (99m)Tc
      coordination and subsequently Annexin V for targeting apoptotic macrophages
      abundant in vulnerable plaques. The in vivo accumulations of imaging probe
      reflected by SPECT and MRI were consistent and accurate in highlighting lesions.
      Intense radioactive signals detected by SPECT facilitated focus recognization and
      quantification, while USPIO-based T2-weighted MRI improved the focal localization
      and volumetry of AS plaques. For subsequent ex vivo planar images, targeting
      effects were further confirmed by immunohistochemistry, including CD-68 and TUNEL
      staining; meanwhile, the degree of concentration was proven to be statistically
      correlated with the Oil Red O staining results. In conclusion, these results
      indicated that the Annexin V-modified hybrid nanoparticle system specifically
      targeted the vulnerable AS plaques containing apoptotic macrophages and could be
      of great value in the invasively accurate detection of vulnerable plaques. 

PMID- 25569778
TI  - Delivering chaplaincy services to veterans at increased risk of suicide.
AB  - The present study quantitatively examines the delivery of chaplaincy services to
      Veterans at increased risk of suicide as well as how chaplains collaborate with
      other healthcare providers. An on-line survey was distributed to the nationwide
      network of U.S. Department of Veterans Affairs chaplains, yielding a response
      rate of 11.91% (N = 118). Most chaplains reported some form of training in
      suicide prevention, approximately half were involved in safety planning, and the
      majority reported not engaging in firearm safety counseling. Chaplaincy services
      were usually delivered through in-person, group, and phone consultations.
      Respondents were generally satisfied with their collaboration with other
      healthcare providers, most often collaborating with psychologists, social
      workers, and counselors. As a descriptive study, the findings serve to inform the
      delivery of chaplaincy services to at-risk Veterans. Recommendations include
      expanding service delivery options, developing competency in safety planning and
      counseling, as well as increasing institutional awareness of chaplaincy services.

PMID- 25569776
TI  - The thalidomide-binding domain of cereblon defines the CULT domain family and is
      a new member of the beta-tent fold.
AB  - Despite having caused one of the greatest medical catastrophies of the last
      century through its teratogenic side-effects, thalidomide continues to be an
      important agent in the treatment of leprosy and cancer. The protein cereblon,
      which forms an E3 ubiquitin ligase compex together with damaged DNA-binding
      protein 1 (DDB1) and cullin 4A, has been recently indentified as a primary target
      of thalidomide and its C-terminal part as responsible for binding thalidomide
      within a domain carrying several invariant cysteine and tryptophan residues. This
      domain, which we name CULT (cereblon domain of unknown activity, binding cellular
      ligands and thalidomide), is also found in a family of secreted proteins from
      animals and in a family of bacterial proteins occurring primarily in delta
      proteobacteria. Its nearest relatives are yippee, a highly conserved eukaryotic
      protein of unknown function, and Mis18, a protein involved in the priming of
      centromeres for recruitment of CENP-A. Searches for distant homologs point to an
      evolutionary relationship of CULT, yippee, and Mis18 to proteins sharing a common
      fold, which consists of two four-stranded beta-meanders packing at a roughly
      right angle and coordinating a zinc ion at their apex. A beta-hairpin inserted
      into the first beta-meander extends across the bottom of the structure towards
      the C-terminal edge of the second beta-meander, with which it forms a cradle
      shaped binding site that is topologically conserved in all members of this fold.
      We name this the beta-tent fold for the striking arrangement of its constituent
      beta-sheets. The fold has internal pseudosymmetry, raising the possibility that
      it arose by duplication of a subdomain-sized fragment. 

PMID- 25569779
TI  - Relationship between chaplain visits and patient satisfaction.
AB  - This prospective study investigated the relationship between chaplain visits and
      patient satisfaction, as measured by Hospital Consumer Assessment of Healthcare
      Providers and Systems (HCAHPS) and Press Ganey surveys from 8,978 patients who
      had been discharged from a tertiary care hospital. Controlling for patients' age,
      gender, race, ethnicity, language, education, faith, general health status, and
      medical conditions, chaplain visits increased the willingness of patients to
      recommend the hospital, as measured by both the HCAHPS survey (regression
      coefficient = 0.07, p < .05) and the Press Ganey survey (0.11, p < .01). On the
      Press Ganey survey, patients visited by chaplains were also more likely to
      endorse that staff met their spiritual needs (0.27, p < .001) and their emotional
      needs (0.10, p < .05). In terms of overall patient satisfaction, patients visited
      by a chaplain were more satisfied on both the Press Ganey survey (0.11, p < .01)
      and on the HCAHPS survey (0.17, p < .05). Chaplains' integration into the
      healthcare team improves patients' satisfaction with their hospital stay.

PMID- 25569781
TI  - Measures of central tendency in chaplaincy, health care, and related research.
AB  - The three measures of central tendency are discussed in this article: the mode,
      the median, and the mean. These measures of central tendency describe data in
      different and important ways, in relation to the level of measurement (nominal,
      ordinal, interval, or ratio) used to obtain the data. The results of published
      research studies, thought experiments, and graphs of frequency and percentage
      distributions of data are used as examples to demonstrate and explain the
      similarities and differences among these summary measures of data. The examples
      include the application of nominal, ordinal, interval, and ratios scales to
      measure pain, anxiety, chaplaincy services, religious behaviors, and treatment
      related preferences, and their respective measures of central tendency. Examples
      of unimodal and bimodal distributions, and differences in the relative locations
      of the median and mean in symmetrical and skewed distributions are also presented
      and discussed. 

PMID- 25569780
TI  - "A remarkable experience of god, shaping us as a family": parents' use of faith
      following child's rare disease diagnosis.
AB  - A child's chronic illness can lead parents to utilize different types of coping,
      including religious beliefs and practices. Previous studies have generally
      focused on life-shortening diagnoses. The present study explored parental use of
      faith when the diagnosis was not life-shortening, using grounded-theory
      qualitative methodology. Data were collected using semi-structured telephone
      interviews with N = 12 parents of children diagnosed with Neuroendocrine
      Hyperplasia of Infancy (NEHI); approximately 50% of the diagnosed population in
      the United States at the time of the interview. Participants used faith to cope
      and make meaning in five ways: parents believed NEHI happened for a reason;
      beliefs provided resilience; parents were sustained by faith communities; beliefs
      affected parents' behavior; and beliefs developed over time. The results suggest
      that chaplains develop means for universal screening for spiritual struggle;
      educating congregational clergy how to support families in which a child has a
      chronic illness; and assisting parents construct meaning of their experience.

PMID- 25569782
TI  - A neural network for learning the meaning of objects and words from a featural
      representation.
AB  - The present work investigates how complex semantics can be extracted from the
      statistics of input features, using an attractor neural network. The study is
      focused on how feature dominance and feature distinctiveness can be naturally
      coded using Hebbian training, and how similarity among objects can be managed.
      The model includes a lexical network (which represents word-forms) and a semantic
      network composed of several areas: each area is topologically organized
      (similarity) and codes for a different feature. Synapses in the model are created
      using Hebb rules with different values for pre-synaptic and post-synaptic
      thresholds, producing patterns of asymmetrical synapses. This work uses a simple
      taxonomy of schematic objects (i.e., a vector of features), with shared features
      (to realize categories) and distinctive features (to have individual members)
      with different frequency of occurrence. The trained network can solve simple
      object recognition tasks and object naming tasks by maintaining a distinction
      between categories and their members, and providing a different role for dominant
      features vs. marginal features. Marginal features are not evoked in memory when
      thinking of objects, but they facilitate the reconstruction of objects when
      provided as input. Finally, the topological organization of features allows the
      recognition of objects with some modified features. 

PMID- 25569783
TI  - Methodological quality of meta-analyses on treatments for chronic obstructive
      pulmonary disease: a cross-sectional study using the AMSTAR (Assessing the
      Methodological Quality of Systematic Reviews) tool.
AB  - BACKGROUND: Meta-analysis (MA) of randomised trials is considered to be one of
      the best approaches for summarising high-quality evidence on the efficacy and
      safety of treatments. However, methodological flaws in MAs can reduce the
      validity of conclusions, subsequently impairing the quality of decision making.
      AIMS: To assess the methodological quality of MAs on COPD treatments. METHODS: A
      cross-sectional study on MAs of COPD trials. MAs published during 2000-2013 were
      sampled from the Cochrane Database of Systematic Reviews and Database of
      Abstracts of Reviews of Effect. Methodological quality was assessed using the
      validated AMSTAR (Assessing the Methodological Quality of Systematic Reviews)
      tool. RESULTS: Seventy-nine MAs were sampled. Only 18% considered the scientific
      quality of primary studies when formulating conclusions and 49% used appropriate
      meta-analytic methods to combine findings. The problems were particularly acute
      among MAs on pharmacological treatments. In 48% of MAs the authors did not report
      conflict of interest. Fifty-eight percent reported harmful effects of treatment.
      Publication bias was not assessed in 65% of MAs, and only 10% had searched non
      English databases. CONCLUSIONS: The methodological quality of the included MAs
      was disappointing. Consideration of scientific quality when formulating
      conclusions should be made explicit. Future MAs should improve on reporting
      conflict of interest and harm, assessment of publication bias, prevention of
      language bias and use of appropriate meta-analytic methods.

PMID- 25569784
TI  - Are large hepatocellular carcinomas still a contraindication for laparoscopic
      liver resection?
AB  - BACKGROUND: Although laparoscopic liver resection has been gradually adopted as
      an attractive option, it is still not indicated for large hepatocellular
      carcinoma (HCC). The aim of this study is to assess the feasibility of
      laparoscopic liver resection for large HCCs. SUBJECTS AND METHODS: A
      retrospective comparative study between 20 patients with HCC >= 5 cm and 103
      patients with HCC <5 cm who underwent laparoscopic liver resection for
      hepatocellular carcinoma from September 2003 until December 2011 at Seoul
      National University Bundang Hospital was performed. RESULTS: In total, 95 men and
      28 women with a mean age of 56.92 +/- 11.28 years were enrolled in this study.
      There were no significant differences in preoperative patient demographics and
      tumor characteristics between the two groups. A major operation was performed
      more frequently in the large tumor group than in the small tumor group. On the
      other hand, intraoperative and postoperative outcomes, the rate of conversion,
      mean operative time, mean blood loss, and mean postoperative hospital stay showed
      no significant difference between the two groups. Also, there was no significant
      difference in rate of morbidity and mortality between the two groups. During a
      median follow-up of 37 months (range, 3-99 months), there was no significant
      difference in disease-free survival and overall survival. CONCLUSIONS:
      Laparoscopic liver resection for an HCC that is larger than 5 cm can be an
      optional treatment in selective cases.

PMID- 25569785
TI  - Use of intraoperative computed tomography for maxillofacial reconstructive
      surgery.
AB  - IMPORTANCE: Intraoperative computed tomography (CT) provides surgeons with real
      time feedback during maxillofacial trauma and reconstructive surgery, which can
      affect intraoperative decision making. OBJECTIVES: To evaluate the time needed to
      perform intraoperative CT scans during maxillofacial surgery, determine any trend
      toward shorter total scan times as experience is gained with the technique, and
      identify the characteristics of cases that required intraoperative revision based
      on the results of intraoperative CT scanning. DESIGN, SETTING, AND PARTICIPANTS:
      A retrospective review was completed for all maxillofacial reconstruction
      procedures that used intraoperative CT between January 1, 2012, and March 31,
      2014. INTERVENTIONS: Patients were cared for by the routine practice pattern of
      the authors. Intraoperative CT scans were obtained for all patients. MAIN
      OUTCOMES AND MEASURES: Time needed for intraoperative CT scan was measured and
      trends were analyzed. Covariates included age, sex, complexity of fracture,
      procedure type, total scan time, surgeon, and need for intraoperative revision
      based on intraoperative CT findings. RESULTS: Thirty-eight cases were identified,
      including 30 males (79%) and 8 females (21%). The mean (SE) age was 37.4 (16.0)
      years (range, 7-75 years). Cases were defined as routine (18 [47%]) or complex
      (20 [53%]). Isolated orbital fractures were the most common fracture (23 [61%])
      in both the routine (14 [78%]) and complex (9 [45%]) cases. The mean (SE) total
      scan time was 14.5 (4.9) minutes (range, 6-27 minutes) and did not differ based
      on complexity (P = .34). Intraoperative revisions were performed in 9 patients
      (24%) and were more common in complex (n = 8) than routine (n = 1) cases (P =
      .004). There was no reduction in total scan time during the study period (P =
      .22). The mean (SE) scan time for the most experienced surgeon was 3.78 (1.53)
      minutes shorter than for the other surgeons as a group (P = .02). CONCLUSIONS AND
      RELEVANCE: Current intraoperative CT scanning techniques are rapid, averaging
      14.5 minutes per case. No decrease in total scan time was noted during the study;
      however, the surgeon most experienced with the CT software had the shortest total
      scan times. Intraoperative revisions were most common in complex cases. We
      recommend surgeons consider the use of intraoperative CT imaging for
      maxillofacial reconstruction, particularly in complex procedures. LEVEL OF
      EVIDENCE: NA.

PMID- 25569786
TI  - Transition-metal-free synthesis of phenanthridinones from biaryl-2-oxamic acid
      under radical conditions.
AB  - Na2S2O8-promoted decarboxylative cyclization of biaryl-2-oxamic acid for
      phenanthridinones has been developed. This work illustrates the first example of
      intramolecular decarboxylative amidation of unactivated arene under transition
      metal-free conditions. Additionally, this approach provides an efficient and
      economical method to access biologically interesting phenanthridinones, an
      important structure motif in many natural products. 

PMID- 25569787
TI  - Energy propagation and network energetic coupling in proteins.
AB  - Understanding how allosteric proteins respond to changes in their environment is
      a major goal of current biological research. We show that these responses can be
      quantified by analyzing protein energy networks using a method recently developed
      in our group. On the basis of this method, we introduce here a quantity named
      energetic coupling, which we show is able to discriminate allosterically active
      mutants of the lactose repressor (LacI) protein, and of the catabolite activator
      protein (CAP), a dynamically driven allosteric protein. Our method assumes that
      allostery and signal transmission can be more accurately described as efficient
      energy propagation, and not as the more widely used atomic motion correlations.
      We demonstrate the validity of this assumption by performing energy-propagation
      simulations. Finally, we present results from energy-propagation simulations
      performed on folded and fully extended conformations of the postsynaptic density
      protein 95 (PSD-95). They show that the protein backbone provides a more
      efficient route for energy transfer, when compared to secondary or tertiary
      contacts. On the basis of this, we propose energy propagation through the
      backbone as a possible explanation for the observation that intrinsically
      disordered proteins can efficiently transmit signals while lacking a well-defined
      tertiary structure. 

PMID- 25569789
TI  - The combination of random mutagenesis and sequencing highlight the role of
      unexpected genes in an intractable organism.

PMID- 25569788
TI  - Transposable elements contribute to activation of maize genes in response to
      abiotic stress.
AB  - Transposable elements (TEs) account for a large portion of the genome in many
      eukaryotic species. Despite their reputation as "junk" DNA or genomic parasites
      deleterious for the host, TEs have complex interactions with host genes and the
      potential to contribute to regulatory variation in gene expression. It has been
      hypothesized that TEs and genes they insert near may be transcriptionally
      activated in response to stress conditions. The maize genome, with many different
      types of TEs interspersed with genes, provides an ideal system to study the
      genome-wide influence of TEs on gene regulation. To analyze the magnitude of the
      TE effect on gene expression response to environmental changes, we profiled gene
      and TE transcript levels in maize seedlings exposed to a number of abiotic
      stresses. Many genes exhibit up- or down-regulation in response to these stress
      conditions. The analysis of TE families inserted within upstream regions of up
      regulated genes revealed that between four and nine different TE families are
      associated with up-regulated gene expression in each of these stress conditions,
      affecting up to 20% of the genes up-regulated in response to abiotic stress, and
      as many as 33% of genes that are only expressed in response to stress. Expression
      of many of these same TE families also responds to the same stress conditions.
      The analysis of the stress-induced transcripts and proximity of the transposon to
      the gene suggests that these TEs may provide local enhancer activities that
      stimulate stress-responsive gene expression. Our data on allelic variation for
      insertions of several of these TEs show strong correlation between the presence
      of TE insertions and stress-responsive up-regulation of gene expression. Our
      findings suggest that TEs provide an important source of allelic regulatory
      variation in gene response to abiotic stress in maize. 

PMID- 25569790
TI  - Transcriptional regulation of the neuropeptide VGF by the neuron-restrictive
      silencer factor/neuron-restrictive silencer element.
AB  - The neurotrophin-inducible gene VGF plays an important role in the maintenance of
      organismal energy balance and in the mediation of hippocampal synaptic activity.
      The regulatory mechanism of VGF transcription is not fully understood. The neuron
      restrictive silencer factor (NRSF) binds with the neuron-restrictive silencer
      element (NRSE), thereby suppressing the transcription of NRSE-containing genes.
      In this study, we show that the NRSE sequence of the VGF gene critically
      regulates the repression of VGF expression in NMB cells. Sequence analysis also
      establishes the presence of two putative NRSEs (NRSE-1 and NRSE-2) in the
      promoter region of the VGF gene. In reporter gene experiments, a more than eight
      fold increase in the promoter activity was observed when both NRSE-1 and NRSE-2
      were deleted. Deletion of NRSE-2 alone did not affect the promoter activity, thus
      indicating that NRSE-1 could be solely responsible for the repression of VGF gene
      expression. Mutations in the NRSE-1 sequence increased promoter activity.
      However, no change in activity was observed when NRSE-1 was coexpressed with
      dominant-negative NRSF, thereby suggesting that endogenous NRSF interacts with
      NRSE-1. Binding of NRSF to NRSE in a sequence-specific manner was confirmed with
      chromatin immunoprecipitation assays, respectively. Furthermore, the
      overexpressed NRSF in PC12 cells significantly suppressed the VGF gene expression
      by interacting with the NRSE located in the VGF promoter region. Our results
      indicate that NRSF plays an important role as a repressor of VGF gene regulation
      in NMB cells through a mechanism that is dependent on VGF-NRSE. 

PMID- 25569791
TI  - Reward positivity is elicited by monetary reward in the absence of response
      choice.
AB  - The neural response to positive and negative feedback differs in their event
      related potentials. Most often this difference is interpreted as the result of a
      negative voltage deflection after negative feedback. This deflection has been
      referred to as the feedback-related negativity component. The reinforcement
      learning model of the feedback-related negativity establishes that this component
      reflects an error monitoring process aimed to increase behavior adjustment
      progressively. However, a recent proposal suggests that the difference observed
      is actually due to a positivity reflecting the rewarding value of positive
      feedbacks - that is, the reward positivity component (RewP). From this it follows
      that RewP could be found even in the absence of any action-monitoring processes.
      We tested this prediction by means of an experiment in which visual target
      stimuli were intermixed with nontarget stimuli. Three types of targets signaled
      money gains, money losses, or the absence of either money gain or money loss,
      respectively. No motor response was required. Event-related potential analyses
      showed a central positivity in a 270-370 ms time window that was elicited by
      target stimuli signaling money gains, as compared with both stimuli signaling
      losses and no-gain/no-loss neutral stimuli. This is the first evidence to show
      that RewP is obtained when stimuli with rewarding values are passively perceived.

PMID- 25569792
TI  - Conflict monitoring and adjustment in the task-switching paradigm under different
      memory load conditions: an ERP/sLORETA analysis.
AB  - The aim of the present study was to examine electrophysiological and behavioral
      changes caused by different memory loads in a task-switching paradigm. A total of
      31 healthy individuals were subjected to a task, in which the stimulus-response
      reversal paradigm was combined with the task-switching paradigm. The event
      related potentials were recorded and the N2 component, an index of conflict
      processing, was measured. In addition, the neural sources of N2 were further
      analyzed by standardized low-resolution brain electromagnetic tomography. The
      event-related potential results showed that high memory load triggered a higher
      N2 mean amplitude. Moreover, the standardized low-resolution brain
      electromagnetic tomography data showed that high memory load caused an increase
      in current densities at the anterior cingulate cortex and the prefrontal cortex
      in the task-switching paradigm. In summary, our findings provide
      electrophysiological evidence to interpret possible influences of memory loads on
      conflict monitoring and modulation during the task switching. These results imply
      that the working memory load overrules the influence of task-switching
      performance on the intensification of cognitive control. 

PMID- 25569793
TI  - An event-related potential study of visual rhyming effects in native and non
      native English speakers.
AB  - English monolinguals and highly proficient, but first language (L1)-dominant,
      Spanish-English and Chinese-English bilinguals made rhyme judgments of visually
      presented English word pairs while behavioral and EEG measures were being
      recorded. Two types of conditions were considered: rhyming and nonrhyming pairs
      that were orthographically dissimilar (e.g. white-fight, child-cough) and those
      that were orthographically similar (e.g. right-fight, dough-cough). Both native
      and non-native English speakers were faster and more accurate in responding to
      nonrhyming than rhyming targets under orthographically dissimilar conditions,
      although the response times of Chinese-English bilinguals differed from those of
      the other groups. All groups were slower and less accurate in responding to
      nonrhyming targets under orthographically similar conditions, with the response
      times and accuracy rates of Spanish-English bilinguals differing from those of
      the other groups. All participant groups showed more negative N450 mean
      amplitudes to nonrhyming compared with rhyming targets, regardless of
      orthographic similarity, and this rhyming effect did not differ across groups
      under the orthographically similar conditions. However, under orthographically
      dissimilar conditions, the rhyming effect was less robust in non-native speakers,
      being modulated by English proficiency. 

PMID- 25569795
TI  - Delayed hyperoxic ventilation attenuates oxygen-induced free radical accumulation
      during early reperfusion after global brain ischemia.
AB  - To compare the effect of immediate and delayed administration of oxygen on the
      accumulation of free radicals in ischemia-reperfusion animal models. Thirty-two
      adult male Mongolian gerbils with microdialysis probes implanted in the right
      hippocampal CA1 were divided randomly into four groups (eight each). One group
      was sham-operated (Sham group) whereas the other three groups were subjected to
      10 min bilateral carotid artery occlusion (BCAO). BCAO-treated animals were then
      subjected to the following: (a) immediate 30% O2 (near normoxia, NO group), (b)
      immediate 100% O2 (hyperoxia, HO group), and (c) 30% O2 for 60 min, followed by
      100% O2 for 60 min (delayed hyperoxia, DHO group). Hippocampal accumulation of
      hydroxyl radicals (*OH) during reperfusion was estimated by measuring 2,3
      dihydroxybenzoic acid (DHBA) and 2,5-DHBA in microdialysis perfusate. Hippocampi
      were removed 2 h after perfusion to measure malondialdehyde, pyruvate
      dehydrogenase activity, indices of lipid peroxidation, and cellular respiration.
      At 24 h after BCAO, the histology of hippocampi was analyzed to rate the injury.
      Immediately after the onset of reperfusion, all groups showed markedly elevated
      DHBA, which returned to baseline over 1-2 h. Compared with the NO group, the HO
      group showed significantly higher peak DHBA and slower recovery. In contrast, the
      DHO group was not significantly different from the NO group in terms of the DHBA
      level. DHO animals also showed significantly lower hippocampal malondialdehyde
      accumulation and higher pyruvate dehydrogenase activity at 2 h after reperfusion
      versus the HO group. Histology analysis also showed animals in the DHO group with
      ameliorated injury compared with the HO group. Hydroxyl radical accumulation was
      more sensitive to O2 during early reperfusion. Delayed hyperoxia may re-establish
      oxidative metabolism while minimizing oxidative stress after CA. 

PMID- 25569794
TI  - Effect of cerebellar transcranial magnetic stimulation on soleus Ia presynaptic
      and reciprocal inhibition.
AB  - Previously, we reported that cerebellar transcranial magnetic stimulation (C-TMS)
      facilitates spinal motoneuronal excitability in resting humans. In this study, we
      aimed to characterize the descending pathway that is responsible for the C-TMS
      associated cerebellar spinal facilitation. We evaluated the effect of C-TMS on
      ipsilateral soleus Ia presynaptic inhibition (PSI) and reciprocal inhibition (RI)
      because the vestibulospinal and reticulospinal tracts project from the cerebellum
      to mediate spinal motoneurons via interneurons associated with PSI. PSI and RI
      were measured with a soleus H-reflex test following operant conditioning using
      electrical stimulation of the common peroneal nerve. C-TMS was delivered before
      test tibial nerve stimulation with conditioning-test interstimulus intervals of
      110 ms. C-TMS did not generate motor-evoked potentials, and it did not increase
      electromyography activity in the ipsilateral soleus muscle, indicating that C-TMS
      does not directly activate the corticospinal tract and motoneurons. However, C
      TMS facilitated the ipsilateral soleus H-reflex and reduced the amount of soleus
      Ia PSI, but not RI. These findings indicate that C-TMS may facilitate the
      excitability of the spinal motoneuron pool via the vestibulospinal or
      reticulospinal tracts associated with PSI. Cerebellar spinal facilitation may be
      useful for assessing the functional connectivity of the cerebellum and vestibular
      nuclei or reticular formation. 

PMID- 25569797
TI  - Parameters of photosynthetic energy partitioning.
AB  - Almost every laboratory dealing with plant physiology, photosynthesis research,
      remote sensing, and plant phenotyping possesses a fluorometer to measure a kind
      of chlorophyll (Chl) fluorescence induction (FLI). When the slow Chl FLI is
      measured with addition of saturating pulses and far-red illumination, the so
      called quenching analysis followed by the so-called relaxation analysis in
      darkness can be realized. These measurements then serve for evaluation of the so
      called energy partitioning, that is, calculation of quantum yields of
      photochemical and of different types of non-photochemical processes. Several
      theories have been suggested for photosynthetic energy partitioning. The current
      work aims to summarize all the existing theories, namely their equations for the
      quantum yields, their meaning and their assumptions. In the framework of these
      theories it is also found here that the well-known NPQ parameter ( [Formula: see
      text] ; Bilger and Bjorkman, 1990) equals the ratio of the quantum yield of
      regulatory light-induced non-photochemical quenching to the quantum yield of
      constitutive non-regulatory non-photochemical quenching (PhiNPQ/Phif,D). A
      similar relationship is also found here for the PQ parameter (PhiP/Phif,D). 

PMID- 25569796
TI  - Neurological abnormalities in full-term asphyxiated newborns and salivary S100B
      testing: the "Cooperative Multitask against Brain Injury of Neonates" (CoMBINe)
      international study.
AB  - BACKGROUND: Perinatal asphyxia (PA) is a leading cause of mortality and morbidity
      in newborns: its prognosis depends both on the severity of the asphyxia and on
      the immediate resuscitation to restore oxygen supply and blood circulation.
      Therefore, we investigated whether measurement of S100B, a consolidated marker of
      brain injury, in salivary fluid of PA newborns may constitute a useful tool for
      the early detection of asphyxia-related brain injury. METHODS: We conducted a
      cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48
      suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels
      measurement longitudinally after birth; routine laboratory variables,
      neurological patterns, cerebral ultrasound and, magnetic resonance imaging were
      performed. The primary end-point was the presence of neurological abnormalities
      at 12-months after birth. RESULTS: S100B salivary levels were significantly
      (P<0.001) higher in newborns with PA than in normal infants. When asphyxiated
      infants were subdivided according to a good (Group A; n = 15) or poor (Group B; n
      = 33) neurological outcome at 12-months, S100B was significantly higher at all
      monitoring time-points in Group B than in Group A or controls (P<0.001, for all).
      A cut-off >3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100%)
      and a specificity of 100% (CI5-95%: 98.6%-100%) as a single marker for predicting
      the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000;
      CI5-95%: 0.987-1.0). CONCLUSIONS: S100B protein measurement in saliva, soon after
      birth, is a useful tool to identify which asphyxiated infants are at risk of
      neurological sequelae.

PMID- 25569798
TI  - High-risk driving attitudes and everyday driving violations of car and racing
      enthusiasts in Ontario, Canada.
AB  - OBJECTIVE: Attitudes and individual difference variables of car and racing
      enthusiasts regarding high-risk behaviors of street racing and stunt driving have
      recently been investigated. Positive attitudes toward high-risk driving,
      personality variables such as driver thrill seeking, and other self-reported
      risky driving acts were associated with these behaviors. However, probable
      relationships among high-risk driving tendencies, everyday driving behaviors, and
      negative road safety outcomes have remained largely unexamined. This study aimed
      to investigate the associations among car and racing enthusiasts' high-risk
      driving attitudes, self-reported everyday driving violations (i.e., ordinary and
      aggressive violations), and self-reported negative outcomes (i.e., collisions and
      driving offense citations). METHOD: A web-based survey was conducted with members
      and visitors of car club and racing websites in Ontario, Canada. Data were
      obtained from 366 participants. The questionnaire included 4 attitude measures
      (1) attitudes toward new penalties for Ontario's Street Racers, Stunt and
      Aggressive Drivers Legislation; (2) attitudes toward new offenses of stunt
      driving under the same legislation; (3) general attitudes toward street racing
      and stunt driving; (4) comparison of street racing with other risky driving
      behaviors-self-reported driving violations (i.e., ordinary and aggressive
      violations); self-reported collisions and offense citations; and background and
      driving questions (e.g., age, driving frequency). RESULTS: Results revealed that
      attitudes toward stunt driving offenses negatively and general attitudes toward
      street racing and stunt driving positively predicted ordinary violations, which,
      in turn, predicted offense citations. Moreover, general attitudes toward street
      racing and stunt driving positively predicted aggressive violations, which, in
      turn, predicted offense citations. CONCLUSION: The findings indicate that
      positive high-risk driving attitudes may be transferring to driving violations in
      everyday traffic, which mediates driving offense citations.

PMID- 25569800
TI  - Quinine-derived thiourea and squaramide catalyzed conjugate addition of alpha
      nitrophosphonates to enones: asymmetric synthesis of quaternary alpha
      aminophosphonates.
AB  - Conjugate addition of alpha-nitrophosphonates to enones was carried out in the
      presence of two sets of organocatalysts, viz. a quinine-thiourea and a quinine
      squaramide. The quinine-thiourea provided the products possessing an alpha
      quaternary chiral center in high enantioselectivities only in the case of
      electron rich enones. On the other hand, the quinine-squaramide was more
      efficient in that a wide variety of electron rich and electron poor enones
      underwent Michael addition of nitrophosphonates to afford the quaternary alpha
      nitrophosphonates in excellent yields and enantioselectivities. The hydrogen
      bonding donor ability of the bifunctional catalyst, as shown in the proposed
      transition states, appears primarily responsible for the observed selectivity.
      However, a favorable pi-stacking between the aryl groups of thiourea/squaramide
      and aryl vinyl ketone also appeared favorable. The reaction was amenable to scale
      up, and the enantioenriched quaternary alpha-nitrophosphonates could be easily
      transformed to synthetically and biologically useful quaternary alpha
      aminophosphonates and other multifunctional molecules. 

PMID- 25569799
TI  - Uropathogenic Escherichia coli superinfection enhances the severity of mouse
      bladder infection.
AB  - Urinary tract infections (UTIs) afflict over 9 million women in America every
      year, often necessitating long-term prophylactic antibiotics. One risk factor for
      UTI is frequent sexual intercourse, which dramatically increases the risk of UTI.
      The mechanism behind this increased risk is unknown; however, bacteriuria
      increases immediately after sexual intercourse episodes, suggesting that physical
      manipulation introduces periurethral flora into the urinary tract. In this paper,
      we investigated whether superinfection (repeat introduction of bacteria) resulted
      in increased risk of severe UTI, manifesting as persistent bacteriuria, high
      titer bladder bacterial burdens and chronic inflammation, an outcome referred to
      as chronic cystitis. Chronic cystitis represents unchecked luminal bacterial
      replication and is defined histologically by urothelial hyperplasia and
      submucosal lymphoid aggregates, a histological pattern similar to that seen in
      humans suffering chronic UTI. C57BL/6J mice are resistant to chronic cystitis
      after a single infection; however, they developed persistent bacteriuria and
      chronic cystitis when superinfected 24 hours apart. Elevated levels of
      interleukin-6 (IL-6), keratinocyte cytokine (KC/CXCL1), and granulocyte colony
      stimulating factor (G-CSF) in the serum of C57BL/6J mice prior to the second
      infection predicted the development of chronic cystitis. These same cytokines
      have been found to precede chronic cystitis in singly infected C3H/HeN mice.
      Furthermore, inoculating C3H/HeN mice twice within a six-hour period doubled the
      proportion of mice that developed chronic cystitis. Intracellular bacterial
      replication, regulated hemolysin (HlyA) expression, and caspase 1/11 activation
      were essential for this increase. Microarrays conducted at four weeks post
      inoculation in both mouse strains revealed upregulation of IL-1 and antimicrobial
      peptides during chronic cystitis. These data suggest a mechanism by which caspase
      1/11 activation and IL-1 secretion could predispose certain women to recurrent
      UTI after frequent intercourse, a predisposition predictable by several serum
      biomarkers in two murine models. 

PMID- 25569801
TI  - Rapid ultrasonic isothermal amplification of DNA with multiplexed melting
      analysis - applications in the clinical diagnosis of sexually transmitted
      diseases.
AB  - We describe a nucleic acid testing (NAT) platform for infectious disease
      diagnostics at the point-of-care, using surface acoustic waves (SAW) to perform a
      multiplexed loop-mediated isothermal amplification (LAMP) test for sexually
      transmitted diseases. The ultrasonic actuation not only enables faster NAT
      reactions but also provides a route towards integrating low-cost, low-power
      molecular diagnostics into disposable sensors. 

PMID- 25569802
TI  - Blockade of Multidrug Resistance-Associated Proteins Aggravates Acute
      Pancreatitis and Blunts Atrial Natriuretic Factor's Beneficial Effect in Rats:
      Role of MRP4 (ABCC4).
AB  - We previously reported that atrial natriuretic factor (ANF) stimulates secretin
      evoked cAMP efflux through multidrug resistance-associated protein 4 (MRP4) in
      the exocrine pancreas. Here we sought to establish in vivo whether this mechanism
      was involved in acute pancreatitis onset in the rat. Rats pretreated with or
      without probenecid (MRPs general inhibitor) were infused with secretin alone or
      with ANF. A set of these animals were given repetitive cerulein injections to
      induce acute pancreatitis. Plasma amylase and intrapancreatic trypsin activities
      were measured and histological examination of the pancreas performed. Secretin
      alone activated trypsinogen but induced no pancreatic histological changes.
      Blockade by probenecid in secretin-treated rats increased trypsin and also
      induced vacuolization, a hallmark of acute pancreatitis. ANF prevented the
      secretin response but in the absence of probenecid. In rats with acute
      pancreatitis, pretreatment with secretin aggravated the disease, but ANF
      prevented secretin-induced changes. Blockade of MRPs in rats with acute
      pancreatitis induced trypsinogen activation and larger cytoplasmic vacuoles as
      well as larger areas of necrosis and edema that were aggravated by secretin but
      not prevented by ANF. The temporal resolution of intracellular cAMP levels seems
      critical in the onset of acute pancreatitis, since secretin-evoked cAMP in a
      context of MRP inhibition makes the pancreas prone to injury in normal rats and
      aggravates the onset of acute pancreatitis. Present findings support a protective
      role for ANF mediated by cAMP extrusion through MRP4 and further suggest that the
      regulation of MRP4 by ANF would be relevant to maintain pancreatic acinar cell
      homeostasis. 

PMID- 25569803
TI  - Oncogenic Role of the Ec Peptide of the IGF-1Ec Isoform in Prostate Cancer.
AB  - IGF-1 is one of the key molecules in cancer biology; however, little is known
      about the role of the preferential expression of the premature IGF-1 isoforms in
      prostate cancer. We have examined the role of the cleaved COO- terminal peptide
      (PEc) of the third IGF-1 isoform, IGF-1Ec, in prostate cancer. Our evidence
      suggests that endogenously produced PEc induces cellular proliferation in the
      human prostate cancer cells (PC-3) in vitro and in vivo, by activating the ERK1/2
      pathway in an autocrine/paracrine manner. PEc overexpressing cells and tumors
      presented evidence of epithelial to mesenchymal transition, whereas the
      orthotopic injection of PEc-overexpressing, normal prostate epithelium cells
      (HPrEC) in SCID mice was associated with increased metastatic rate. In humans,
      the IGF-1Ec expression was detected in prostate cancer biopsies, where its
      expression correlates with tumor stage. Our data describes the action of PEc in
      prostate cancer biology and defines its potential role in tumor growth,
      progression and metastasis. 

PMID- 25569804
TI  - Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating
      Mitochondrial Function and Biogenesis.
AB  - Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its
      clinical application is limited because of its dose-dependent cardiotoxicity.
      DOX's cardiotoxicity involves increased oxidative/nitrative stress, impaired
      mitochondrial function in cardiomyocytes/endothelial cells and cell death.
      Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well
      tolerated in humans, with antioxidant, antiinflammatory and recently discovered
      antitumor properties. We aimed to explore the effects of CBD in a well
      established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy
      was characterized by increased myocardial injury (elevated serum creatine kinase
      and lactate dehydrogenase levels), myocardial oxidative and nitrative stress
      (decreased total glutathione content and glutathione peroxidase 1 activity,
      increased lipid peroxidation, 3-nitrotyrosine formation and expression of
      inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and
      poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline
      in ejection fraction and left ventricular fractional shortening). DOX also
      impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy
      number, mRNA expression of peroxisome proliferator-activated receptor gamma
      coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen
      related receptor alpha), reduced mitochondrial function (attenuated complex I and
      II activities) and decreased myocardial expression of uncoupling protein 2 and 3
      and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly
      improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell
      death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function
      and biogenesis. These data suggest that CBD may represent a novel
      cardioprotective strategy against DOX-induced cardiotoxicity, and the above
      described effects on mitochondrial function and biogenesis may contribute to its
      beneficial properties described in numerous other models of tissue injury. 

PMID- 25569805
TI  - Loss of Allograft Inflammatory Factor-1 Ameliorates Experimental Autoimmune
      Encephalomyelitis by Limiting Encephalitogenic CD4 T-Cell Expansion.
AB  - Experimental autoimmune encephalomyelitis (EAE), an animal model of human
      multiple sclerosis (MS), is mediated by myelin-specific autoreactive T cells that
      cause inflammation and demyelination in the central nervous system (CNS), with
      significant contributions from activated microglia and macrophages. The molecular
      bases for expansion and activation of these cells, plus trafficking to the CNS
      for peripheral cells, are not fully understood. Allograft inflammatory factor-1
      (Aif-1) (also known as ionized Ca(2+) binding adapter-1 [Iba-1]) is induced in
      leukocytes in MS and EAE; here we provide the first assessment of Aif-1 function
      in this setting. After myelin oligodendrocyte glycoprotein peptide (MOG35-55)
      immunization, Aif-1-deficient mice were less likely than controls to develop EAE
      and had less CNS leukocyte infiltration and demyelination; their spinal cords
      contained fewer CD4 T cells and microglia and more CD8 T cells. These mice also
      showed significantly less splenic CD4 T-cell expansion and activation, plus
      decreased proinflammatory cytokine expression. These findings identify Aif-1 as a
      potent molecule that promotes expansion and activation of CD4 T cells, plus
      elaboration of a proinflammatory cytokine milieu, in MOG35-55-induced EAE and as
      a potential therapeutic target in MS. 

PMID- 25569807
TI  - Government must produce "credible evidence" to support seven day working, BMA
      says.

PMID- 25569806
TI  - A genetic strategy for probing the functional diversity of magnetosome formation.
AB  - Model genetic systems are invaluable, but limit us to understanding only a few
      organisms in detail, missing the variations in biological processes that are
      performed by related organisms. One such diverse process is the formation of
      magnetosome organelles by magnetotactic bacteria. Studies of model magnetotactic
      alpha-proteobacteria have demonstrated that magnetosomes are cubo-octahedral
      magnetite crystals that are synthesized within pre-existing membrane compartments
      derived from the inner membrane and orchestrated by a specific set of genes
      encoded within a genomic island. However, this model cannot explain all
      magnetosome formation, which is phenotypically and genetically diverse. For
      example, Desulfovibrio magneticus RS-1, a delta-proteobacterium for which we lack
      genetic tools, produces tooth-shaped magnetite crystals that may or may not be
      encased by a membrane with a magnetosome gene island that diverges significantly
      from those of the alpha-proteobacteria. To probe the functional diversity of
      magnetosome formation, we used modern sequencing technology to identify hits in
      RS-1 mutated with UV or chemical mutagens. We isolated and characterized mutant
      alleles of 10 magnetosome genes in RS-1, 7 of which are not found in the alpha
      proteobacterial models. These findings have implications for our understanding of
      magnetosome formation in general and demonstrate the feasibility of applying a
      modern genetic approach to an organism for which classic genetic tools are not
      available.

PMID- 25569809
TI  - Next generation of cardiovascular studies: transcriptional responses of the human
      myocardium during cardiac surgery.

PMID- 25569808
TI  - Association between progressive retinal nerve fiber layer loss and longitudinal
      change in quality of life in glaucoma.
AB  - IMPORTANCE: Evaluation of structural optic nerve damage is a fundamental part of
      diagnosis and management of glaucoma. However, the relationship between
      structural measurements and disability associated with the disease is not well
      characterized. Quantification of this relationship may help validate structural
      measurements as markers directly relevant to quality of life. OBJECTIVE: To
      evaluate the relationship between rates of retinal nerve fiber layer (RNFL) loss
      and longitudinal changes in quality of life in glaucoma. DESIGN, SETTING, AND
      PARTICIPANTS: Observational cohort study including 260 eyes of 130 patients with
      glaucoma followed up for a mean (SD) of 3.5 (0.7) years. All patients had
      repeatable visual field defects on standard automated perimetry (SAP) at
      baseline. The 25-item National Eye Institute Visual Function Questionnaire (NEI
      VFQ-25) was performed annually, and spectral-domain optical coherence tomography
      and SAP were performed at 6-month intervals. A joint model was used to
      investigate the association between change in NEI VFQ-25 Rasch-calibrated scores
      and change in RNFL thickness, adjusting for confounding socioeconomic and
      clinical variables. MAIN OUTCOMES AND MEASURES: Association between change in
      binocular RNFL thickness (RNFL thickness in the better eye at each point) and
      change in NEI VFQ-25 scores. RESULTS: Progressive binocular RNFL thickness loss
      was associated with worsening of NEI VFQ-25 scores over time. In a multivariable
      model adjusting for baseline disease severity and the rate of change in binocular
      SAP sensitivity, each 1-MUm-per-year loss of RNFL thickness was associated with a
      decrease of 1.3 units (95% CI, 1.02-1.56) per year in NEI VFQ-25 scores (P <
      .001). After adjusting for the contribution from SAP, 26% (95% CI, 12%-39%) of
      the variability of change in NEI VFQ-25 scores was associated uniquely with
      change in binocular RNFL thickness. The P value remained less than .001 after
      adjusting for potential confounding factors. CONCLUSIONS AND RELEVANCE:
      Progressive binocular RNFL thickness loss was associated with longitudinal loss
      in quality of life, even after adjustment for progressive visual field loss.
      These findings suggest that rates of binocular RNFL change are valid markers for
      the degree of neural loss in glaucoma with significant relationship to glaucoma
      associated disability.

PMID- 25569810
TI  - A randomized controlled trial of adaptive support ventilation mode to wean
      patients after fast-track cardiac valvular surgery.
AB  - BACKGROUND: Adaptive support ventilation can speed weaning after coronary artery
      surgery compared with protocolized weaning using other modes. There are no data
      to support this mode of weaning after cardiac valvular surgery. Furthermore,
      control group weaning times have been long, suggesting that the results may
      reflect control group protocols that delay weaning rather than a real advantage
      of adaptive support ventilation. METHODS: Randomized (computer-generated sequence
      and sealed opaque envelopes), parallel-arm, unblinded trial of adaptive support
      ventilation versus physician-directed weaning after adult fast-track cardiac
      valvular surgery. The primary outcome was duration of mechanical ventilation.
      Patients aged 18 to 80 yr without significant renal, liver, or lung disease or
      severe impairment of left ventricular function undergoing uncomplicated elective
      valve surgery were eligible. Care was standardized, except postoperative
      ventilation. In the adaptive support ventilation group, target minute ventilation
      and inspired oxygen concentration were adjusted according to blood gases. A
      spontaneous breathing trial was carried out when the total inspiratory pressure
      of 15 cm H2O or less with positive end-expiratory pressure of 5 cm H2O. In the
      control group, the duty physician made all ventilatory decisions. RESULTS: Median
      duration of ventilation was statistically significantly shorter (P = 0.013) in
      the adaptive support ventilation group (205 [141 to 295] min, n = 30) than that
      in controls (342 [214 to 491] min, n = 31). Manual ventilator changes and alarms
      were less common in the adaptive support ventilation group, and arterial blood
      gas estimations were more common. CONCLUSION: Adaptive support ventilation
      reduces ventilation time by more than 2 h in patients who have undergone fast
      track cardiac valvular surgery while reducing the number of manual ventilator
      changes and alarms.

PMID- 25569811
TI  - pi(+)-pi interactions between (hetero)aromatic amine cations and the graphitic
      surfaces of pyrogenic carbonaceous materials.
AB  - Many organic compounds of environmental concern contain amine groups that are
      positively charged at environmental pH. Here we present evidence that
      (hetero)aromatic amine cations can act as pi acceptors in forming pi(+)-pi
      electron donor-acceptor (EDA) interactions with the pi electron-rich,
      polyaromatic surface of pyrogenic carbonaceous materials (PCMs) (i.e., biochar,
      black carbon, and graphene). The pi(+)-pi EDA interactions combine a cation-pi
      force with a pi-pi EDA force resulting from charge polarization of the ring's
      quadrupole. Adsorption on a biochar and reference adsorbent graphite was
      conducted of triazine herbicides, substituted anilines, heterocyclic aromatic
      amines, and other amines whose charge is insulated from the aromatic ring. When
      normalized for the hydrophobic effect, the adsorption increased with decreasing
      pH as the amines became ionized, even on graphite that had no significant fixed
      or variable charge. The cationic pi acceptor (quinolinium ion) was competitively
      displaced more effectively by the pi acceptor 2,4-dinitrobenzene than by the pi
      donor naphthalene. The maximum electrostatic potential of organocations computed
      with density functional theory was found to be a strong predictor of the pi(+)-pi
      EDA interaction. The pi(+)-pi EDA interaction was disfavored by electropositive
      alkyl substituents and by charge delocalization into additional rings. Amines
      whose charge was insulated from the ring fell far out of the correlation (more
      positive free energy of adsorption). Identifying and characterizing this novel
      pi(+)-pi EDA interaction on PCMs will help in predicting the fate of
      organocations in both natural and engineered systems.

PMID- 25569812
TI  - Triggered exchange of anionic for neutral guests inside a cationic coordination
      cage.
AB  - Molecular encapsulation processes under the control of an external trigger play a
      major role in biological signal transduction processes and enzyme catalysis.
      Here, we present an artificial mimic of a controllable host system that forms via
      self-assembly from a simple bis-monodentate ligand and Pd(II) cations. The
      resulting interpenetrated double cage features three consecutive pockets which
      initially contain one tetrafluoroborate anion, each. Activation of this host
      system with two halide anions triggers a conformational change that renders the
      central pocket susceptible to the uptake of small neutral guest molecules.
      Thereby, the pentacationic cage expels the central anion and replaces it with a
      neutral molecule to give a hexacationic species. The cage structures prior and
      after the halide triggered binding of benzene were examined by X-ray
      crystallography, ESI MS, and NMR techniques. The kinetics and thermodynamics of
      the encapsulation of benzene, cyclohexane, and norbornadiene are compared. 

PMID- 25569814
TI  - Mesoscale assemblies of iron oxide nanocubes as heat mediators and image contrast
      agents.
AB  - Iron oxide nanocubes (IONCs) represent one of the most promising iron-based
      nanoparticles for both magnetic resonance image (MRI) and magnetically mediated
      hyperthermia (MMH). Here, we have set a protocol to control the aggregation of
      magnetically interacting IONCs within a polymeric matrix in a so-called magnetic
      nanobead (MNB) having mesoscale size (200 nm). By the comparison with individual
      coated nanocubes, we elucidate the effect of the aggregation on the specific
      adsorption rates (SAR) and on the T1 and T2 relaxation times. We found that while
      SAR values decrease as IONCs are aggregated into MNBs but still keeping
      significant SAR values (200 W/g at 300 kHz), relaxation times show very
      interesting properties with outstanding values of r2/r1 ratio for the MNBs with
      respect to single IONCs. 

PMID- 25569815
TI  - Comparison of Warner-Bratzler shear force values between round and square cross
      section cores from cooked beef and pork Longissimus muscle.
AB  - This study was conducted to investigate the effect of core sampling on Warner
      Bratzler shear force evaluations of beef and pork loins (Longissimus thoracis et
      lumborum muscles) and to determine the relationship between them. Steaks of 2.54
      cm from beef and pork loins were cooked and five round cross-section cores and
      five square cross-section cores of each steak were taken for shear force
      evaluation. Core sampling influenced both beef and pork shear force values with
      higher (P<0.05) average values and standard deviations for square cross-section
      cores. There was a strong and linear relationship (P<0.01) between round and
      square cross-section cores for beef (R(2)=0.78), pork (R(2)=0.70) and for
      beef+pork (R(2)=0.82) samples. These results indicate that it is feasible to use
      square cross-section cores in Warner-Bratzler shear force protocol as an
      alternative and potential method to standardize sampling for shear force
      measurements.

PMID- 25569813
TI  - Proanthocyanidin-rich date seed extract protects against chemically induced
      hepatorenal toxicity.
AB  - A hydroacetone extract was prepared from seeds of Phoenix dactylifera L. var.
      Khalas, which is an industrial by-product of date processing. The
      proanthocyanidin nature of the extract (coded as DTX) was characterized by
      phytochemical and nuclear magnetic resonance (NMR) analyses. The total
      phenol/proanthocyanidin content and antioxidant activity of DTX were estimated by
      Folin-Ciocalteu, vanillin-sulfuric acid, and 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      assays, respectively. The hepatorenal protective activity of DTX was evaluated
      using CCl4-induced toxicity model in rats, in comparison with silymarin (SYL).
      Results of the histopathological examination and measurements of various
      hepatorenal serum indices and tissue biochemical markers demonstrated that DTX
      displayed marked protective potential against CCl4-induced liver and kidney
      injury at 100 mg/kg/rat. Relative to the control CCl4-intoxicated group,
      pretreatment with DTX significantly (P<.001) suppressed the elevated serum levels
      of alanine aminotransferase and aspartate aminotransferase (ALT and AST),
      alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total cholesterol
      (TC), low-density lipoprotein cholesterol (LDL-C), bilirubin, creatinine, and
      calcium, whereas it significantly (P<.001) increased the diminished serum levels
      of high-density lipoprotein cholesterol (HDL-C) and total protein (TP). Moreover,
      DTX significantly decreased malondialdehyde (MDA) formation and increased TP
      synthesis in hepatorenal tissues compared with the intoxicated control. The
      improvement in biochemical parameters by DTX was observed in a dose-dependent
      manner and confirmed by restoration of normal histological features. The acute
      toxicity test of DTX in rats revealed safety of the extract. This study reveals
      that DTX enhances the recovery from xenobiotics-induced toxicity initiated by
      free radicals. 

PMID- 25569816
TI  - Management of bilateral malignant ovarian germ cell tumors: a MITO-9
      retrospective study.
AB  - OBJECTIVES: Bilaterality is rare in malignant ovarian germ cell tumors (MOGTs).
      The bilateral ovarian involvement represents a critical issue when diagnosed in
      young women desiring to preserve fertility. The aim of this study was to evaluate
      clinical characteristic and management of patients bilateral MOGTs. METHODS:
      Patients affected by bilateral MOGT and treated at MITO group centers were
      reviewed. RESULTS: In 145 patients with MOGTs, 5.5% were bilateral. Three
      patients were affected by dysgerminoma (associated with bilateral gonadoblastoma
      in 1), 2 by immature teratoma, 2 by mixed germ cell tumors, and 1 by embryonal
      carcinoma. International Federation of Gynecology and Obstetrics stage was 3 IB,
      1 IC, 3 IIIC, and 1 IV. Three patients received radical surgery, and the patient
      with dysgerminoma associated with gonadoblastoma received bilateral adnexectomy.
      Four patients received fertility-sparing surgery; 2 patients received unilateral
      salpingo-oophorectomy and contralateral cystectomy; in 2 patients, the ovaries
      were completely transformed in neoplastic tissue; suspecting a contralateral
      dysgerminoma histology, a unilateral salpingo-oophorectomy and contralateral
      biopsy were performed, and the contralateral neoplastic ovary was left
      unresected. Six patients received adjuvant chemotherapy. Seven patients are
      disease free after a median follow-up of 54 months. The patient affected by
      embryonal carcinoma died of disease. Two patients resumed menstruation, and one
      had a pregnancy. A compromised ovarian function was found in 2 patients, and they
      were addressed to oocyte cryopreservation. CONCLUSIONS: Bilateral MOGTs have a
      good prognosis. In dysgerminoma histology, residual disease could be left to
      spare fertility. An oncological and reproductive function follow-up is
      recommended.

PMID- 25569817
TI  - Efficacy of raloxifene hydrochloride for the prevention of health care problems
      in patients who undergo surgery for endometrial cancer: a multicenter randomized
      clinical trial.
AB  - OBJECTIVE: Removal of the ovaries is common during surgery for endometrial
      cancer. However, because loss of the ovaries can cause several health problems in
      patients, strategies for the prevention of such problems need to be established.
      Hence, we decided to conduct a multicenter randomized clinical trial to assess
      the effect of raloxifene on bone mineral density (BMD), bone metabolism, and the
      lipid profile of patients who had undergone surgery for patients with endometrial
      cancer. MATERIALS AND METHODS: Patients with endometrial cancer were enrolled
      after treatment. The participants were randomized into 2 groups: group 1 included
      39 women who received alfacalcidol (1 MUg/d) alone and group 2 included 37 women
      who received alfacalcidol and the test drug, raloxifene hydrochloride, at a dose
      of 60 mg/d. The BMD of lumbar spine and femoral neck, serum bone markers, as well
      as lipid profile parameters were evaluated at enrollment as well as 6, 12, and 24
      months after the enrollment. The primary efficacy end point was the percentage
      change from baseline to 24 months in lumbar spine (L2-L4) and femoral neck BMD.
      RESULTS: Sixty-four women completed the 24-month study. At 24 months, the lumbar
      and femoral neck BMDs were significantly increased in group 2 compared with group
      1 (3.5% vs -0.8% and 2.3% vs -2.8%, respectively). In group 2, low-density
      lipoprotein-cholesterol levels were significantly reduced by 13.6% and serum N
      terminal telopeptide of type I collagen as well as bone-specific alkaline
      phosphatase values were significantly reduced by 16.7% and 25.7%, respectively.
      The patients who received adjuvant therapy for endometrial cancer showed a
      significantly higher response to raloxifene (5.8% vs 1.9%). Recurrence was
      detected in 2 (2.6%) patients in group 1. No severe adverse events were noted in
      any patient during the study period. CONCLUSIONS: Raloxifene exerts positive
      effects on BMD, bone metabolism, and lipid profile parameters and could provide
      an improved therapeutic option for patients with endometrial cancer.

PMID- 25569818
TI  - Measuring homonegativity: psychometric analysis of Herek's attitudes toward
      lesbians and gay men scale (ATLG) in Colombia, South America.
AB  - The empirical study of negative attitudes toward gay and lesbian people
      (homonegativity) is a way to understand the reason for its prevalence. The aim of
      this study was to examine the psychometric properties of a Spanish version of the
      Attitudes Toward Lesbians and gay men scale (ATLG). A total of 359 undergraduate
      students were recruited from two different cities in Colombia, South America.
      Participants' attitudes toward gays and lesbian people were assessed using the
      ATLG Scale and the Homophobia Scale; anxiety was measured using a short version
      of the Zung Self-Rating Anxiety Scale. Internal consistency analyses have shown
      that the ATLG Scale is a reliable measure of homonegativity in a Colombian
      sample. In addition, principal components analyses, as well as convergent and
      divergent validity analyses have confirmed that the ATLG Scale is a valid and
      reliable measure of homonegativity in the Colombian context and support its use
      as a research instrument.

PMID- 25569819
TI  - Carboxyl-peptide plane stacking is important for stabilization of buried E305 of
      Trichoderma reesei Cel5A.
AB  - Hydrogen bonds or salt bridges are usually formed to stabilize the buried
      ionizable residues. However, such interactions do not exist for two buried
      residues D271 and E305 of Trichoderma reesei Cel5A, an endoglucanase. Mutating
      D271 to alanine or leucine improves the enzyme thermostability quantified by the
      temperature T50 due to the elimination of the desolvation penalty of the aspartic
      acid. However, the same mutations for E305 decrease the enzyme thermostability.
      Free energy calculations based on the molecular dynamics simulation predict the
      thermostability of D271A, D271L, and E305A (compared to WT) in line with the
      experimental observation but overestimate the thermostability of E305L. Quantum
      mechanical calculations suggest that the carboxyl-peptide plane stacking
      interactions occurring to E305 but not D271 are important for the carboxyl group
      stabilization. For the protonated carboxyl group, the interaction energy can be
      as much as about -4 kcal/mol for parallel stacking and about -7 kcal/mol for T
      shaped stacking. For the deprotonated carboxyl group, the largest interaction
      energies for parallel stacking and T-shaped stacking are comparable, about -7
      kcal/mol. The solvation effect generally weakens the interaction, especially for
      the charged system. A search of the carboxyl-peptide plane stacking in the PDB
      databank indicates that parallel stacking but not T-shaped stacking is quite
      common, and the most probable distance between the two stacking fragments is
      close to the value predicted by the QM calculations. This work highlights the
      potential role of carboxyl amide pi-pi stacking in the stabilization of aspartic
      acid and glutamic acid in proteins. 

PMID- 25569820
TI  - Metallomics and NMR-based metabolomics of Chlorella sp. reveal the synergistic
      role of copper and cadmium in multi-metal toxicity and oxidative stress.
AB  - Industrial wastewaters often contain high levels of metal mixtures, in which
      metal mixtures may have synergistic or antagonistic effects on aquatic organisms.
      A combination of metallomics and nuclear magnetic resonance spectroscopy (NMR)
      based metabolomics was employed to understand the consequences of multi-metal
      systems (Cu, Cd, Pb) on freshwater microalgae. Morphological characterization,
      cell viability and chlorophyll a determination of metal-spiked Chlorella sp.
      suggested synergistic effects of Cu and Cd on growth inhibition and toxicity.
      While Pb has no apparent effect on Chlorella sp. metabolome, a substantial
      decrease of sucrose, amino acid content and glycerophospholipid precursors in Cu
      spiked microalgae revealed Cu-induced oxidative stress. Addition of Cd to Cu
      spiked cultures induced more drastic metabolic perturbations, hence we confirmed
      that Cu and Cd synergistically influenced photosynthesis inhibition, oxidative
      stress and membrane degradation. Total elemental analysis revealed a significant
      decrease in K, and an increase in Na, Mg, Zn and Mn concentrations in Cu-spiked
      cultures. This indicated that Cu is more toxic to Chlorella sp. as compared to Cd
      or Pb, and the combination of Cu and Cd has a strong synergistic effect on
      Chlorella sp. oxidative stress induction. Oxidative stress is confirmed by liquid
      chromatography tandem mass spectrometry analysis, which demonstrated a drastic
      decrease in the GSH/GSSG ratio solely in Cu-spiked cultures. Interestingly, we
      observed Cu-facilitated Cd and Pb bioconcentration in Chlorella sp. The absence
      of phytochelatins and an increment of extracellular polymeric substances (EPS)
      yields in Cu-spiked cultures suggested that the mode of bioconcentration of Cd
      and Pb is through adsorption of free metals onto the algal EPS rather than
      intracellular chelation to phytochelatins. 

PMID- 25569821
TI  - Generation of spin currents by surface plasmon resonance.
AB  - Surface plasmons, free-electron collective oscillations in metallic
      nanostructures, provide abundant routes to manipulate light-electron interactions
      that can localize light energy and alter electromagnetic field distributions at
      subwavelength scales. The research field of plasmonics thus integrates nano
      photonics with electronics. In contrast, electronics is also entering a new era
      of spintronics, where spin currents play a central role in driving devices.
      However, plasmonics and spin-current physics have so far been developed
      independently. Here we report the generation of spin currents by surface plasmon
      resonance. Using Au nanoparticles embedded in Pt/BiY(2)Fe(5)O(12) bilayer films,
      we show that, when the Au nanoparticles fulfill the surface-plasmon-resonance
      conditions, spin currents are generated across the Pt/BiY(2)Fe(5)O(12) interface.
      This spin-current generation cannot be explained by conventional heating effects,
      requiring us to introduce nonequilibrium magnons excited by surface-plasmon
      induced evanescent electromagnetic fields in BiY(2)Fe(5)O(12). This plasmonic
      spin pumping integrates surface plasmons with spin-current physics, opening the
      door to plasmonic spintronics.

PMID- 25569822
TI  - Regionally-varying combustion sources of the January 2013 severe haze events over
      eastern China.
AB  - Thick haze plagued northeastern China in January 2013, strongly affecting both
      regional climate and human respiratory health. Here, we present dual carbon
      isotope constrained (Delta(14)C and delta(13)C) source apportionment for
      combustion-derived black carbon aerosol (BC) for three key hotspot regions
      (megacities): North China Plain (NCP, Beijing), the Yangtze River Delta (YRD,
      Shanghai), and the Pearl River Delta (PRD, Guangzhou) for January 2013. BC, here
      quantified as elemental carbon (EC), is one of the most health-detrimental
      components of PM2.5 and a strong climate warming agent. The results show that
      these severe haze events were equally affected (~ 30%) by biomass combustion in
      all three regions, whereas the sources of the dominant fossil fuel component was
      dramatically different between north and south. In the NCP region, coal
      combustion accounted for 66% (46-74%, 95% C.I.) of the EC, whereas, in the YRD
      and PRD regions, liquid fossil fuel combustion (e.g., traffic) stood for 46% (18
      66%) and 58% (38-68%), respectively. Taken together, these findings suggest the
      need for a regionally-specific description of BC sources in climate models and
      regionally-tailored mitigation to combat severe air pollution events in East
      Asia.

PMID- 25569824
TI  - Nanopore-based assay for detection of methylation in double-stranded DNA
      fragments.
AB  - DNA methylation is an epigenetic modification of DNA in which methyl groups are
      added at the 5-carbon position of cytosine. Aberrant DNA methylation, which has
      been associated with carcinogenesis, can be assessed in various biological fluids
      and potentially can be used as markers for detection of cancer. Analytically
      sensitive and specific assays for methylation targeting low-abundance and
      fragmented DNA are needed for optimal clinical diagnosis and prognosis. We
      present a nanopore-based direct methylation detection assay that circumvents
      bisulfite conversion and polymerase chain reaction amplification. Building on our
      prior work, we used methyl-binding proteins (MBPs), which selectively label the
      methylated DNA. The nanopore-based assay selectively detects methylated DNA/MBP
      complexes through a 19 nm nanopore with significantly deeper and prolonged
      nanopore ionic current blocking, while unmethylated DNA molecules were not
      detectable due to their smaller diameter. Discrimination of hypermethylated and
      unmethylated DNA on 90, 60, and 30 bp DNA fragments was demonstrated using sub-10
      nm nanopores. Hypermethylated DNA fragments fully bound with MBPs are
      differentiated from unmethylated DNA at 2.1- to 6.5-fold current blockades and
      4.5- to 23.3-fold transport durations. Furthermore, these nanopore assays can
      detect the CpG dyad in DNA fragments and could someday profile the position of
      methylated CpG sites on DNA fragments. 

PMID- 25569823
TI  - Simulating the complex cell design of Trypanosoma brucei and its motility.
AB  - The flagellate Trypanosoma brucei, which causes the sleeping sickness when
      infecting a mammalian host, goes through an intricate life cycle. It has a rather
      complex propulsion mechanism and swims in diverse microenvironments. These
      continuously exert selective pressure, to which the trypanosome adjusts with its
      architecture and behavior. As a result, the trypanosome assumes a diversity of
      complex morphotypes during its life cycle. However, although cell biology has
      detailed form and function of most of them, experimental data on the dynamic
      behavior and development of most morphotypes is lacking. Here we show that
      simulation science can predict intermediate cell designs by conducting specific
      and controlled modifications of an accurate, nature-inspired cell model, which we
      developed using information from live cell analyses. The cell models account for
      several important characteristics of the real trypanosomal morphotypes, such as
      the geometry and elastic properties of the cell body, and their swimming
      mechanism using an eukaryotic flagellum. We introduce an elastic network model
      for the cell body, including bending rigidity and simulate swimming in a fluid
      environment, using the mesoscale simulation technique called multi-particle
      collision dynamics. The in silico trypanosome of the bloodstream form displays
      the characteristic in vivo rotational and translational motility pattern that is
      crucial for survival and virulence in the vertebrate host. Moreover, our model
      accurately simulates the trypanosome's tumbling and backward motion. We show that
      the distinctive course of the attached flagellum around the cell body is one
      important aspect to produce the observed swimming behavior in a viscous fluid,
      and also required to reach the maximal swimming velocity. Changing details of the
      flagellar attachment generates less efficient swimmers. We also simulate
      different morphotypes that occur during the parasite's development in the tsetse
      fly, and predict a flagellar course we have not been able to measure in
      experiments so far. 

PMID- 25569825
TI  - [Effect of the summer Olympic Games on Hungarian suicide rates].
AB  - In our study, we set out to investigate whether there is a significant
      relationship between the count (raw rate) of suicides committed and the summer
      Olympic Games in such an achievement-oriented society like the Hungarian one,
      where summer Olympic Games receive extremely considerable attention. For our
      study, we examined the suicide cases occurring over 15706 days between 1 January
      1970 and 31 December 2012 (43 years), separately for each gender. Because of the
      age-specific characteristics of suicide, the effect of the Olympic Games was
      analysed for the middle-aged (30-60 year-old) and the elderly (over 60 year-old)
      generations, as well as for the whole gender specific population. The role of the
      summer Olympic Games was examined with the help of time series intervention
      analysis after the cyclical and seasonal components have been removed. Based on
      our results, the effect of the Olympic Games is significant for the middle-aged
      (30-60 year-old) population. Neither in the older male, nor in any of the female
      age groups could a relationship between suicide and this sports event be
      detected. In summary, the Olympic Games seem to decrease the rate of suicide
      among middle-aged men slightly but significantly. In the interpretation of our
      results we emphasise the importance of the complex approach of suicidal behavior.

PMID- 25569826
TI  - [A clinical method for the investigation of spirituality].
AB  - The purpose of the Religion Psychology Department of the National Institute of
      Psychiatry and Neurology, Budapest, was to provide hospital care and cure for
      psychiatric patients belonging to different religions and spiritual movements.
      Modern psychiatric treatment integrates the three main dimensions of psychiatry:
      the biological, the sociotherapeutic and the psychotherapeutic. To this we have
      added a fourth field involving the spiritual life. The department was organized
      by therapeutic community principles. At the beginning our work was made almost
      impossible by an extreme confusion of worldviews and theological concepts which
      hindered clients' communication with each other as well as the work of
      sociotherapy and psychotherapy. Thus it became unavoidable to elaborate a common
      language and value system. This task was accomplished by searching for common
      denominators. We traced back most problems to two main factors. The first had to
      do with the essence of humanness, with the main driving force of the human
      personality. The second related to the final value system by which human actions
      are judged. We located the first factor in the human aspiration for development
      in both the inner and outer life and in the need for community. In our department
      mutual help, the promotion of development and usefulness for the community came
      to be regarded the standards of behavior. We used these standards as coordinates
      in our discussions. These made possible the work of psychotherapy as well as life
      in the therapeutic community.

PMID- 25569827
TI  - [Conduct symptoms and emotional decision making in non-clinical adolescents].
AB  - BACKGROUND: In adults with antisocial personality disorder, literature data
      indicate alterations in emotional decision making and in the working of the
      prefrontal cortex. Similar alterations were described in adolescents with
      psychopathic traits, however, a dimensional link was not established between
      behavioral variables and variables associated with decision making. The aim of
      the present study was to describe the relationship between externalizing symptoms
      and emotional decision making in non-clinical adolescents. METHODS: Originally
      57, 7th-10th grade students between 13-16 years participated in the study after
      informed consent, but the data of 4 adolescents were not used because of
      incomplete data-set (N=53; 24 girls and 29 boys; age=14.7 +/- 1.0 years, mean +/-
      SD). The parent version of the Strengths and Difficulties Questionnaire (SDQ) was
      used to assess behavioral problems. The Iowa Gambling Task (IGT) performance and
      Raven IQ measures were also assessed. RESULTS: The number of summarized risky
      choices was positively correlated with Conduct Problems Scale of SDQ (r=0.31,
      p<0.05). While the number of risky choices was not correlated with conduct
      problems in the first 20 selections (r=0.11, p=n.s.), a marked positive
      correlation was present in the above measures in the last 20 selections (r=0.28,
      p<0.05). The number of risky choices did not depend on Raven IQ, age, and other
      behavioral scales of SDQ. CONCLUSIONS: Even subthreshold conduct symptoms are
      associated with altered emotional decision making in adolescents, what might be
      important in the development of antisocial behavior.

PMID- 25569828
TI  - [Regular physical activity and mental health. The role of exercise in the
      prevention of, and intervention in depressive disorders].
AB  - In our review we examine the relationship between physical activity and mental
      health; especially we determine the effectiveness of exercise in the prevention
      and treatment of depression. Over the past two decades the literature in the area
      of physical activity and mental health has been growing. However it seems that
      the findings and evidences not being utilized by mental health agencies and
      health practitioners. Depression is the most common disorder in the world,
      generally has a higher prevalence among women. In our study we overview and
      demonstrate that the exercise is a powerful intervention for prevention and
      treatment not only in non-clinical but also in clinical levels of depression. In
      sub-clinical levels of depression the meta-analytic findings and population
      surveys suggest that the exercise is associated with a significant moderate
      reduction of depression in different groups by gender and age; as well as a
      physically active lifestyle associates with lower levels of depression. In
      clinical levels of depression the physical activity is an effective tool in the
      prevention, studies support an association between higher levels of physical
      activity and lower levels of depression. In the treatment of clinical depression
      the randomized-controlled trials suggest the clear positive effects of exercise.
      This effect is similar to psychotherapeutic interventions and it was appeared
      under relatively short time (4-8 weeks). The exercise is one of the most
      important preventive health-related behaviors. Our review suggests a protective
      effect from activity on the development of clinical levels of depression and
      depressive symptoms. In addition the randomized controlled trials support a
      causal connection between exercise and reduction of depression. In sum the
      reviewed studies clearly support the antidepressant effect of exercise.

PMID- 25569829
TI  - Everyday functions and needs of individuals with disability: a reliability and
      validity study based on the principles of the ICF.
AB  - INTRODUCTION: The goal of this study was to develop and validate a questionnaire
      to measure everyday functions of individuals with disability based on the
      principles of the International Classification of Functioning, Disability, and
      Health (ICF). METHODS: Participants consisted of 1116 individuals. The final
      sample was representative for the following criteria: disability, gender, age,
      and residence. The questionnaire consisted of 4 sections. In addition to general
      and demographic questions, we developed 258 statements about everyday functioning
      based on the items from the ICF. RESULTS: The Cronbach alphas showed adequate
      internal reliability for the different scales: range of Cronbach alphas on the
      main sample: .624 to .904; range of Cronbach alphas on the test-retest sample:
      .627 to .921. Correlations with validating scales were typically high.
      Individuals with disability showed lower mean scores in each area compared to
      controls but the profiles of the different groups with disability varied across
      areas. The data also showed that physical status by itself does not determine
      everyday functioning. Several participants across groups showed that despite
      severe physical disability, one may exhibit high values of everyday functioning
      and well-being. CONCLUSION: Our questionnaire is a valid and reliable method to
      measure everyday functioning in individuals with different disabilities. The
      various versions of the questionnaire (computerized, paper-pencil, easy to
      understand) ensure that everyone's functioning and well-being can be assessed.

PMID- 25569830
TI  - [Quality of life of newly diagnosed, treatment naive children and adolescents
      with attention-deficit hyperactivity disorder].
AB  - INTRODUCTION: Attention-deficit hyperactivity disorder (ADHD) is one of the most
      prevalent childhood psychiatric disorder, it affects around 3-12% of the
      children. ADHD is associated with numerous social and emotional impairments.
      Quality of life (QoL) studies of children with ADHD established low QoL in the
      most cases. Our aim was to examine QoL of children with ADHD according to the
      following aspects: age, children's self-report and parentproxy report, and we
      also would like to compare them with healthy control group along several
      dimensions of QoL. METHODS: The clinical group consist of a treatmant naive group
      of children with ADHD, who were just diagnosed in the Vadaskert Hospital. The
      healthy control group consist of children from elementary schools. The children
      of control group do not have ADHD and do not stand under psychological or
      psychiatrical treatment. In our study we applied Mini International
      Neuropsychiatric Interview Kid and Intervertat Lebensqualitat Kindern und
      Jugendlichen questionare. RESULTS: Compared children with ADHD to healthy control
      group they have significantly lower QoL at many areas (school, peer realtions,
      generally) due their self report. By parent's proxy report children with ADHD
      have lower QoL according to all of the QoL domains. Parents of children with ADHD
      reported significantly lower QoL for their children in the most areas (school,
      family, peer realtion, mental state, generally) then the affected children.
      Adolescent with ADHD have lower QoL in 3 domains (school, peer relations,
      generally) than children with ADHD, while children with ADHD have lower QoL in
      one dimension (being alone) compared with adolescents with ADHD. CONCLUSION:
      Based on our results children with ADHD compared to healthy control group have
      lower QoL in many dimensions and there are age-related differences in the
      assessment of QoL. Additionally, our study draw the attention to the differences
      of QoL assessment between children and parents.

PMID- 25569831
TI  - [Psychological perspectives of abortion care -- when, what and how can
      psychotherapeutic assistance help during pregnancy termination].
AB  - Research data on the psychological consequences of induced abortion show that
      almost 20 per cent of women are affected by related, long term psychological
      complications such as anxiety disorders, depression and PTSD. The aim of this
      review is to summarise support possibilities which are significant to prevent
      recurrent abortions and psychiatric problems following surgical interventions.
      Besides acute crisis management, the primary tasks of psychological interventions
      must also include screening women at high risk of later psychological problems
      and recurring abortions, supporting bereavement work when experience of loss
      emerges; as well as professional psychotherapeutic assistance in cases of
      complicated grief. 

PMID- 25569832
TI  - [Psychometric properties of the Hungarian version of the Codependence
      Questionnaire].
AB  - The purpose of this study is to assess the internal consistency of the subscales
      of the Hungarian Version of the Codependent Questionnaire (CdQ, Roehling &
      Gaumond, 1996). Thus, a reliable measurement of codependency for professionals
      become available in Hungary. The Hungarian Version of the Codependent
      Questionnaire enables professionals to identify codependent individuals. METHODS:
      Our sample (N=137) was recruited from the general population and from self-help
      groups (82 individuals); and patients with borderline personality disorder (55
      individuals) were recruited as clinical control group. The reliability of the
      questionnaire was assessed by Cronbach's alfa and principal component analysis.
      In addition, in order to investigate the latent structure, factors analyses and
      hierarchical cluster analysis were used. RESULTS: Based on our results, the
      Cronbach's alfa values of the subscales of 'control', 'reliability' and
      'intimacy' indicate appropriate reliability, however, the subscale of
      'enmeshment' indicates poor reliability. The originally assumed factor structure
      is not supported by the results of the statistical analyses. The subscales are
      not separate from each other, which is also indicated by the correlations of the
      total scores of the subscales. CONCLUSION: The reliability of the Hungarian
      Version of the Codependent Questionnaire is nearly identical to the original
      data, except for one subscale ('enmeshment subscale'). Based on these results the
      Hungarian Version of the Codependent Questionnaire is considered to be reliable.
      Besides the Hungarian adaptation, the strength of this study is the investigation
      of a clinical sample. The use of the questionnaire is recommended without the
      subscale of 'enmeshment' and further 5 items, and it is suggested to use as one
      scale.

PMID- 25569833
TI  - Correlation Between Histomorphometric and Micro-computed Tomography Analysis of
      Periapical Lesions in Mice Model.
AB  - Periapical lesions are processes mediated from bacterial invasion on the pulp
      tissue, which results in inflammatory process and bone resorption. Animal models
      have been used for the study of cell interactions and inflammatory responses
      involved in periapical lesion. The use of different methods for morphometric
      evaluation of this lesion has been reported. However, due to the limitation of 2D
      methods, computerized microtomography (uCT) has been indicated. Therefore, the
      aim of this study was to evaluate the correlation between the histomorphometric
      measures of periapical lesions and the uCT analysis obtained in an animal
      experimental model. Briefly, the periapical lesions were induced by pulp exposal
      and after the experimental periods (7, 21 and 42 days) the mice were euthanized.
      The mandibles were evaluated under the uCT scanning and then were subjected to
      the routine histologic procedures, stained with hematoxilin and eosin. The
      periapical lesions were measured by the specific softwares of each technique. A
      weak correlation among the histomorphometric measurement and the 2D uCT analysis
      (r(2)= .204) and between the histomorphometric measurement and the 3D uCT
      analysis (r(2)= .237) was observed. A strong correlation between the 2D and 3D
      uCT analysis (r(2)= .867) was observed. Thereby, it can be concluded that the uCT
      is a method that allows a precise volumetric scanning and represents an important
      tool for morphometric evaluation.

PMID- 25569834
TI  - Palladium-catalyzed oxidative deacetonative coupling of 4-aryl-2-methyl-3-butyn-2
      ols with H-phosphonates.
AB  - An efficient and generally applicable protocol for palladium-catalyzed oxidative
      deacetonative coupling of 4-aryl-2-methyl-3-butyn-2-ols with dialkyl H
      phosphonates has been developed. This methodology provides a new and practical
      route to alkynylphosphonates using the inexpensive 4-aryl-2-methyl-3-butyn-2-ols
      as the alkyne sources. This reaction could also be performed with aryl bromides,
      2-methyl-3-butyne-2-ol and dialkyl H-phosphonates using the cheap 2-methyl-3
      butyne-2-ol as an alkyne source. 

PMID- 25569836
TI  - Enhanced tolerance to stretch-induced performance degradation of stretchable MnO2
      based supercapacitors.
AB  - The performance of many stretchable electronics, such as energy storage devices
      and strain sensors, is highly limited by the structural breakdown arising from
      the stretch imposed. In this article, we focus on a detailed study on materials
      matching between functional materials and their conductive substrate, as well as
      enhancement of the tolerance to stretch-induced performance degradation of
      stretchable supercapacitors, which are essential for the design of a stretchable
      device. It is revealed that, being widely utilized as the electrode material of
      the stretchable supercapacitor, metal oxides such as MnO2 nanosheets have serious
      strain-induced performance degradation due to their rigid structure. In
      comparison, with conducting polymers like a polypyrrole (PPy) film as the
      electrochemically active material, the performance of stretchable supercapacitors
      can be well preserved under strain. Therefore, a smart design is to combine PPy
      with MnO2 nanosheets to achieve enhanced tolerance to strain-induced performance
      degradation of MnO2-based supercapacitors, which is realized by fabricating an
      electrode of PPy-penetrated MnO2 nanosheets. The composite electrodes exhibit a
      remarkable enhanced tolerance to strain-induced performance degradation with well
      preserved performance over 93% under strain. The detailed morphology and
      electrochemical impedance variations are investigated for the mechanism analyses.
      Our work presents a systematic investigation on the selection and matching of
      electrode materials for stretchable supercapacitors to achieve high performance
      and great tolerance to strain, which may guide the selection of functional
      materials and their substrate materials for the next-generation of stretchable
      electronics. 

PMID- 25569837
TI  - Millisecond laser ablation of molybdenum target in reactive gas toward MoS2
      fullerene-like nanoparticles with thermally stable photoresponse.
AB  - As a promising material for photoelectrical application, MoS2 has attracted
      extensive attention on its facile synthesis and unique properties. Herein, we
      explored a novel strategy of laser ablation to synthesize MoS2 fullerene-like
      nanoparticles (FL-NPs) with stable photoresponse under high temperature.
      Specifically, we employed a millisecond pulsed laser to ablate the molybdenum
      target in dimethyl trisulfide gas, and as a result, the molybdenum nanodroplets
      were ejected from the target and interacted with the highly reactive ambient gas
      to produce MoS2 FL-NPs. In contrast, the laser ablation in liquid could only
      produce core-shell nanoparticles. The crucial factors for controlling final
      nanostructures were found to be laser intensity, cooling rate, and gas
      reactivity. Finally, the MoS2 FL-NPs were assembled into a simple photoresponse
      device which exhibited excellent thermal stability, indicating their great
      potentialities for high-temperature photoelectrical applications. 

PMID- 25569838
TI  - High incidence is not high exposure: what proportion of prevention trial
      participants are exposed to HIV?
AB  - OBJECTIVE: Randomized clinical trials of HIV prevention in high-risk populations
      of women often assume that all participants have similar exposure to HIV.
      However, a substantial fraction of women enrolled in the trial may have no or low
      exposure to HIV. Our objective was to estimate the proportion of women exposed to
      HIV throughout a hypothetical high-risk study population. METHODS: A stochastic
      individual-based model was developed to simulate the sexual behavior and the risk
      of HIV acquisition for a cohort of sexually active HIV-uninfected women in high
      HIV prevalence settings. Key behavior and epidemic assumptions in the model were
      based on published studies on HIV transmission in South Africa. The prevalence of
      exposure, defined as the proportion of women who have sex with HIV-infected
      partner, and HIV incidence were evaluated. RESULTS: Our model projects that in
      communities with HIV incidence rate of 1 per 100 person years, only 5-6% of women
      are exposed to HIV annually while in communities with an HIV incidence of 5 per
      100 person years 20-25% of women are exposed to HIV. Approximately 70% of the new
      infections are acquired from partners with asymptomatic HIV. CONCLUSIONS:
      Mathematical models suggest that a high proportion of women enrolled in HIV
      prevention trials may be unexposed to HIV even when incidence rates are high. The
      relationship between HIV exposure and other risk factors should be carefully
      analyzed when future clinical trials are planned.

PMID- 25569842
TI  - Corrigendum.

PMID- 25569840
TI  - Persistent and transient Listeria monocytogenes strains from retail deli
      environments vary in their ability to adhere and form biofilms and rarely have
      inlA premature stop codons.
AB  - Based on recent risk assessments, up to 83% of listeriosis cases from deli meat
      in the United States are predicted to be from ready-to-eat deli meats
      contaminated during processing at retail grocery stores. Listeria monocytogenes
      is known to use sanitizer tolerance and biofilm formation to survive, but
      interplay of these mechanisms along with virulence potential and persistence
      mechanisms specific to deli environments had yet to be elucidated. In this study,
      442 isolates from food and nonfood contact surfaces in 30 retail delis over 9
      months were tested for inlA premature stop codons (PMSCs); inlA encodes InlA,
      which is necessary to cause listeriosis. A total of 96 isolates, composed of 23
      persistent and 73 transient strains, were tested for adhesion and biofilm-forming
      ability and sanitizer tolerance. Only 10/442 isolates had inlA PMSCs (p<0.001).
      Strains with PMSCs were not persistent, even in delis with other persistent
      strains. Most (7/10) PMSC-containing isolates were collected from food contact
      surfaces (p<0.001); 6/10 PMSC-containing isolates were found in moderate
      prevalence delis (p<0.05). Persistent strains had enhanced adhesion on day 1 of a
      5-day adhesion-biofilm formation assay. However, there was no significant
      difference in sanitizer tolerance between persistent and transient strains.
      Results suggest that foods contaminated with persistent L. monocytogenes strains
      from the retail environment are (1) likely to have wild-type virulence potential
      and (2) may persist due to increased adhesion and biofilm formation capacity
      rather than sanitizer tolerance, thus posing a significant public health risk. 

PMID- 25569839
TI  - Guidelines for monitoring autophagy in Caenorhabditis elegans.
AB  - The cellular recycling process of autophagy has been extensively characterized
      with standard assays in yeast and mammalian cell lines. In multicellular
      organisms, numerous external and internal factors differentially affect autophagy
      activity in specific cell types throughout the stages of organismal ontogeny,
      adding complexity to the analysis of autophagy in these metazoans. Here we
      summarize currently available assays for monitoring the autophagic process in the
      nematode C. elegans. A combination of measuring levels of the lipidated Atg8
      ortholog LGG-1, degradation of well-characterized autophagic substrates such as
      germline P granule components and the SQSTM1/p62 ortholog SQST-1, expression of
      autophagic genes and electron microscopy analysis of autophagic structures are
      presently the most informative, yet steady-state, approaches available to assess
      autophagy levels in C. elegans. We also review how altered autophagy activity
      affects a variety of biological processes in C. elegans such as L1 survival under
      starvation conditions, dauer formation, aging, and cell death, as well as
      neuronal cell specification. Taken together, C. elegans is emerging as a powerful
      model organism to monitor autophagy while evaluating important physiological
      roles for autophagy in key developmental events as well as during adulthood. 

PMID- 25569843
TI  - Delta-aminolevulinic acid dehydratase (deltaALAD) activity in four free-living
      bird species exposed to different levels of lead under natural conditions.
AB  - The purposes of this study were: (1) to determine the deltaALAD activity and
      deltaALAD ratio in blood of four free-living bird species (Griffon vulture, Eagle
      owl, Slender-billed gull and Audouin's gull); (2) and to investigate the
      correlations between deltaALAD activity/ratio and Pb concentrations in blood
      samples. A decrease was observed in deltaALAD activity in Griffon vultures and
      Eagle owls exposed to Pb. In addition, negative relationships were found between
      deltaALAD ratio or deltaALAD activity and Log blood Pb levels in Griffon vultures
      and Eagle owls, and these relationships were stronger in areas with the highest
      Pb exposure. We provide equations that may be helpful to estimate deltaALAD
      activity and deltaALAD ratio using blood Pb concentrations. Regarding gull
      species, deltaALAD activity found in the present study may be considered the
      normal activity in Slender-billed gull and Audouin's gull species, since very low
      blood Pb concentrations and no correlations were found in these species. Although
      both deltaALAD activity and deltaALAD ratio are sensitive biomarkers of Pb
      exposure and effect in birds, the use of deltaALAD ratio may improve the results.
      Besides, this study provides blood threshold concentrations at which Pb bears
      effects on deltaALAD enzyme (5ug/dl in Eagle owl; 8ug/dl in Griffon vulture; and
      probably >2ug/dl in Slender-billed gull and Audouin's gull). Our findings show
      that Eagle owl seems to be more sensitive to deltaALAD enzymatic inhibition by Pb
      than Griffon vultures. Eagle owls and Griffon vultures exhibited up to 79% and
      94% decrease in deltaALAD activity when blood Pb concentrations exceeded 19 and
      30ug/dl, respectively. Regarding the effects related with deltaALAD inhibition,
      significant negative correlations were found between deltaALAD activity and
      hematocrit in Eagle owls and Griffon vultures, which may be related to
      compensatory response associated with a decrease in deltaALAD activity. In
      addition, an effect on creatine kinase activity and total proteins in plasma was
      found in Griffon vultures. The significant negative correlations found between
      deltaALAD activity and tGSH in Griffon vulture, and between deltaALAD activity
      and Log CAT activity in Eagle owls, may be related to a protective response of
      antioxidant system against reactive oxygen species (ROS). The negative
      relationship found between deltaALAD activity and TBARS levels in Griffon vulture
      is probably related to an induction of lipid peroxidation by ROS that may be
      generated by deltaALA accumulation when deltaALAD activity is depressed.
      deltaALAD activity and deltaALAD ratio in blood are suggested as important
      nondestructive biomarkers for Pb exposure and effect for future biomonitoring
      studies in Griffon vulture and Eagle owl. Further studies are recommended to
      provide new data on Pb concentrations at which deltaALAD activity is affected in
      different wild bird species and to elucidate why different species tolerate Pb in
      different ways. 

PMID- 25569841
TI  - Long term mental health outcomes of Finnish children evacuated to Swedish
      families during the second world war and their non-evacuated siblings: cohort
      study.
AB  - OBJECTIVES: To compare the risks of admission to hospital for any type of
      psychiatric disorder and for four specific psychiatric disorders among adults who
      as children were evacuated to Swedish foster families during the second world war
      and their non-evacuated siblings, and to evaluate whether these risks differ
      between the sexes. DESIGN: Cohort study. SETTING: National child evacuation
      scheme in Finland during the second world war. PARTICIPANTS: Children born in
      Finland between 1933 and 1944 who were later included in a 10% sample of the 1950
      Finnish census ascertained in 1997 (n = 45,463; women: n = 22,021; men: n =
      23,442). Evacuees in the sample were identified from war time government records.
      MAIN OUTCOME MEASURE: Adults admitted to hospital for psychiatric disorders
      recorded between 1971 and 2011 in the Finnish hospital discharge register.
      METHODS: We used Cox proportional hazards models to estimate the association
      between evacuation to temporary foster care in Sweden during the second world war
      and admission to hospital for a psychiatric disorder between ages 38 and 78
      years. Fixed effects methods were employed to control for all unobserved social
      and genetic characteristics shared among siblings. RESULTS: Among men and women
      combined, the risk of admission to hospital for a psychiatric disorder did not
      differ between Finnish adults evacuated to Swedish foster families and their non
      evacuated siblings (hazard ratio 0.89, 95% confidence interval 0.64 to 1.26).
      Evidence suggested a lower risk of admission for any mental disorder (0.67, 0.44
      to 1.03) among evacuated men, whereas for women there was no association between
      evacuation and the overall risk of admission for a psychiatric disorder (1.21,
      0.80 to 1.83). When admissions for individual psychiatric disorders were
      analyzed, evacuated girls were significantly more likely than their non-evacuated
      sisters to be admitted to hospital for a mood disorder as an adult (2.19, 1.10 to
      4.33). CONCLUSIONS: The Finnish evacuation policy was not associated with an
      increased overall risk of admission to hospital for a psychiatric disorder in
      adulthood among former evacuees. In fact, evacuation was associated with a
      marginally reduced risk of admission for any psychiatric disorder among men.
      Among women who had been evacuated, however, the risk of being admitted to
      hospital for a mood disorder was increased.

PMID- 25569844
TI  - Bioaccumulation of organohalogenated compounds in sharks and rays from the
      southeastern USA.
AB  - Organohalogenated compounds are widespread in the marine environment and can be a
      serious threat to organisms in all levels of aquatic food webs, including
      elasmobranch species. Information about the concentrations of POPs (persistent
      organic pollutants) and of MeO-PBDEs (methoxylated polybrominated diphenyl
      ethers) in elasmobranchs is scarce and potential toxic effects are poorly
      understood. The aims of the present study were therefore to investigate the
      occurrence of multiple POP classes (PCBs, PBDEs, DDXs, HCB, CHLs) and of MeO
      PBDEs in various elasmobranch species from different trophic levels in estuarine
      and marine waters of the southeastern United States. Overall, levels and patterns
      of PCBs, PBDEs, DDXs, HCB, CHLs and of MeO-PBDEs varied according to the species,
      maturity stage, gender and habitat type. The lowest levels of POPs were found in
      Atlantic stingrays and the highest levels were found in bull sharks. As both
      species are respectively near the bottom and at top of the trophic web, with
      juvenile bull sharks frequently feeding on Atlantic stingrays, these findings
      further suggest a bioaccumulation and biomagnification process with trophic
      position. MeO-PBDEs were not detected in Atlantic stingrays, but were found in
      all shark species. HCB was not found in Atlantic stingrays, bonnetheads or lemon
      sharks, but was detected in the majority of bull sharks examined. Comparison with
      previous studies suggests that Atlantic stingrays may be experiencing toxic
      effects of PCBs and DDXs on their immune system. However, the effect of these
      compounds on the health of shark species remains unclear. 

PMID- 25569845
TI  - Trends in sepsis and infection sources in the United States. A population-based
      study.
AB  - RATIONALE: Stakeholders seek to monitor processes and outcomes of care among
      patients with sepsis, but use of administrative data for sepsis surveillance is
      controversial. Prior studies using only principal diagnoses from claims data have
      shown a trend of rising sepsis incidence with falling infection incidence,
      implying that administrative data are inaccurate for sepsis surveillance.
      OBJECTIVES: Because a sepsis diagnosis often modifies an infection site
      diagnosis, we sought to investigate trends in sepsis and infection using both
      principal and secondary diagnoses in administrative data. METHODS: This was a
      retrospective cohort study. We used data from the Nationwide Inpatient Sample
      years 2003 to 2009 to identify age-standardized, population-based trends in
      sepsis and infection using all available diagnosis codes. Infection sites were
      defined as bacteremia, pneumonia, urinary tract, skin/soft tissue, and
      gastrointestinal; codes for septicemia, sepsis, severe sepsis, and septic shock
      were used to identify "sepsis." We identified patients with infection and
      mechanical ventilation to estimate incidence of severe sepsis without requiring
      specific claims for sepsis or acute organ failure. MEASUREMENTS AND MAIN RESULTS:
      We identified 53.9 million adult infection hospitalizations during the years 2003
      to 2009; average age was 63 years, 61% of patients were women, and 70% reported
      white race, 14% black, and 11% Hispanic ethnicity. Incidence of hospitalizations
      with an infection claim increased from 3,147/100,000 U.S. residents in 2003 to
      3,480/100,000 in 2009 (11% increase), whereas hospitalizations with sepsis claims
      increased from 359/100,000 to 535/100,000 residents during the same time frame
      (49% increase); P = 0.009 between infection and sepsis trends. The proportion of
      infection hospitalizations with a sepsis claim increased from 7.5% in 2003 to
      11.5% in 2009 (54% increase). The incidence of hospitalizations with both an
      infection and mechanical ventilation claim during 2003 was 173/100,000 as
      compared with 251/100,000 in 2009 (45% increase); P = 0.76 compared with sepsis
      trends. CONCLUSIONS: Sepsis claims are increasing at a greater rate than
      infection claims but are not inversely related. Trends in sepsis are similar to
      trends in infection cases requiring mechanical ventilation. Further studies
      should seek to identify the optimal algorithms to identify sepsis within
      administrative data and explore potential mechanisms for the increasing incidence
      of infection and sepsis in the United States.

PMID- 25569846
TI  - Interactive effects of ultraviolet-B radiation and pesticide exposure on DNA
      photo-adduct accumulation and expression of DNA damage and repair genes in
      Xenopus laevis embryos.
AB  - Pesticide use and ultraviolet-B (UVB) radiation have both been suggested to
      adversely affect amphibians; however, little is known about their interactive
      effects. One potential adverse interaction could involve pesticide-induced
      dysregulation of DNA repair pathways, resulting in greater numbers of DNA photo
      adducts from UVB exposure. In the present study, we investigated the interactive
      effects of UVB radiation and two common pesticides (endosulfan and alpha
      cypermethrin) on induction of DNA photo-adducts and expression of DNA damage and
      repair related genes in African clawed frog (Xenopus laevis) embryos. We examined
      13 genes that are, collectively, involved in stress defense, cell cycle arrest,
      nucleotide excision repair (NER), base excision repair, mismatch repair, DNA
      repair regulation, and apoptosis. We exposed X. laevis embryos to 0, 25, and 50
      MUg/L endosulfan or 0, 2.5, and 5.0 MUg/L alpha-cypermethrin for 96 h, with
      environmentally relevant exposures of UVB radiation during the last 7 h of the 96
      h exposure. We measured the amount of cyclobutane pyrimidine dimers (CPDs) and
      mRNA abundance of the 13 genes among treatments including control, pesticide
      only, UVB only, and UVB and pesticide co-exposures. Each of the co-exposure
      scenarios resulted in elevated CPD levels compared to UVB exposure alone,
      suggesting an inhibitory effect of endosulfan and alpha-cypermethrin on CPD
      repair. This is attributed to results indicating that alpha-cypermethrin and
      endosulfan reduced mRNA abundance of XPA and HR23B, respectively, to levels that
      may affect the initial recognition of DNA lesions. In contrast, both pesticides
      increased transcript abundance of CSA and MUTL. In addition, mRNA abundance of
      HSP70 and GADD45alpha were increased by endosulfan and mRNA abundance of XPG was
      increased by alpha-cypermethrin. XPC, HR23B, XPG, and GADD45alpha exhibited
      elevated mRNA concentrations whereas there was a reduction in MUTL transcript
      concentrations in UVB-alone treatments. It appeared that even though expression
      of XPC and CSA were induced by exposure to UVB or pesticides, XPA was the
      limiting factor in the NER pathway. Our results suggest that pesticides may
      increase the accumulation of UVB-induced DNA photo-adducts and one likely
      mechanism is the alteration of critical NER gene expression. The present study
      provides important implications for evaluating the combined risks of pesticide
      usage and potentially increasing UVB radiation in aquatic ecosystems.

PMID- 25569847
TI  - Expression and immunohistochemical localization of the cytochrome P450 isoform
      356A1 (CYP356A1) in oyster Crassostrea gigas.
AB  - Cytochrome P450 family (CYP) is a group of proteins virtually found in all living
      organisms. The main role of most CYPs is to metabolize endo and xenobiotics. Most
      of the studies on CYP have been carried out in mammals and other vertebrates,
      however recently a growing interest has been devoted to the identification of CYP
      isoforms in invertebrates. A gene belonging to the CYP sub-family, CYP356A1, was
      identified in sanitary sewage-exposed Pacific oysters, Crassostrea gigas. Through
      heterologous expression, we produced CYP356A1 purified protein and raised a mouse
      polyclonal antibody. Dot blot tests showed that oysters exposed in situ for 14
      days to untreated urban effluent discharges had significantly higher levels of
      CYP356A1 in digestive gland. Using immunohistochemical techniques we observed
      that the lining epithelial cells of mantle, stomach and intestine showed a strong
      CYP356A1 staining, but the mucus and secretory cells were negative. Digestive
      diverticulum parenchyma and gills lining cells showed strong CYP356A1 reaction,
      while the filamentary rod (connective tissue) was negative. Free cells, as
      hemocytes and brown cells also showed CYP356A1 immunoreactions indicating the
      presence of biotransformation activity in these cells. Male germ cells at early
      stages expressed CYP356A1 but not sperm mature cells, suggesting that this
      protein could be involved in the male gonadal development. This study shows the
      use of a specific antibody to a mollusk CYP isoform and that this protein is
      inducible in oysters environmentally exposed to urban sewage effluents. 

PMID- 25569849
TI  - Asthma attacks: how can we reduce the risks?

PMID- 25569848
TI  - Membrane contact sites, gateways for lipid homeostasis.
AB  - Maintaining the proper lipid composition of cellular membranes is critical for
      numerous cellular processes but mechanisms of membrane lipid homeostasis are not
      well understood. There is growing evidence that membrane contact sites (MCSs),
      regions where two organelles come in close proximity to one another, play major
      roles in the regulation of intracellular lipid composition and distribution. MCSs
      are thought to mediate the exchange of lipids and signals between organelles. In
      this review, we discuss how lipid exchange occurs at MCSs and evidence for roles
      of MCSs in regulating lipid synthesis and degradation. We also discuss how
      networks of organelles connected by MCSs may modulate cellular lipid homeostasis
      and help determine organelle lipid composition. 

PMID- 25569850
TI  - Bayesian history matching of complex infectious disease models using emulation: a
      tutorial and a case study on HIV in Uganda.
AB  - Advances in scientific computing have allowed the development of complex models
      that are being routinely applied to problems in disease epidemiology, public
      health and decision making. The utility of these models depends in part on how
      well they can reproduce empirical data. However, fitting such models to real
      world data is greatly hindered both by large numbers of input and output
      parameters, and by long run times, such that many modelling studies lack a formal
      calibration methodology. We present a novel method that has the potential to
      improve the calibration of complex infectious disease models (hereafter called
      simulators). We present this in the form of a tutorial and a case study where we
      history match a dynamic, event-driven, individual-based stochastic HIV simulator,
      using extensive demographic, behavioural and epidemiological data available from
      Uganda. The tutorial describes history matching and emulation. History matching
      is an iterative procedure that reduces the simulator's input space by identifying
      and discarding areas that are unlikely to provide a good match to the empirical
      data. History matching relies on the computational efficiency of a Bayesian
      representation of the simulator, known as an emulator. Emulators mimic the
      simulator's behaviour, but are often several orders of magnitude faster to
      evaluate. In the case study, we use a 22 input simulator, fitting its 18 outputs
      simultaneously. After 9 iterations of history matching, a non-implausible region
      of the simulator input space was identified that was 10(11) times smaller than
      the original input space. Simulator evaluations made within this region were
      found to have a 65% probability of fitting all 18 outputs. History matching and
      emulation are useful additions to the toolbox of infectious disease modellers.
      Further research is required to explicitly address the stochastic nature of the
      simulator as well as to account for correlations between outputs.

PMID- 25569852
TI  - A phytotoxic active substance in the decomposing litter of the fern Gleichenia
      japonica.
AB  - The fern Gleichenia japonica often dominates plant communities by forming large
      monospecific stands throughout the temperate to tropical Asia. The objective of
      this study was the investigation of allelopathic property and substances of the
      decomposing litter of the fern to evaluate the possible involvement of its
      allelopathy in the domination. An aqueous methanol extract of G. japonica litter
      inhibited the growth of garden cress (Lepidium sativum), lettuce (Lactuca
      sativa), barnyard grass (Echinochloa crus-galli), and ryegrass (Lolium
      multiflorum). This result suggests that G. japonica litter contains growth
      inhibitory substances. The extract was purified by chromatography while
      monitoring the inhibitory activity, and a growth inhibitory substance was
      isolated. The chemical structure of the substance was determined by spectral data
      to be a novel compound, 13-O-beta-fucopyranosyl-3beta-hydroxymanool. This
      compound inhibited root and shoot growth of garden cress and barnyard grass at
      concentrations ranging from 89.7 to 271 MUM for 50% inhibition. In addition, the
      compound had potent growth inhibitory activity with the soil taken from near the
      colony. The concentration of the compound in soil under a pure colony of G.
      japonica was 790 MUM, suggesting that the compound may contribute to the
      establishment of monocultural stands by this fern.

PMID- 25569853
TI  - Protein Precipitation Behavior of Condensed Tannins from Lotus pedunculatus and
      Trifolium repens with Different Mean Degrees of Polymerization.
AB  - The precipitation of bovine serum albumin (BSA), lysozyme (LYS), and alfalfa leaf
      protein (ALF) by two large- and two medium-sized condensed tannin (CT) fractions
      of similar flavan-3-ol subunit composition is described. CT fractions isolated
      from white clover flowers and big trefoil leaves exhibited high-purity profiles
      by 1D/2D NMR and purities >90% (determined by thiolysis). At pH 6.5, large CTs
      with a mean degree of polymerization (mDP) of ~18 exhibited similar protein
      precipitation behaviors and were significantly more effective than medium CTs
      (mDP ~9). Medium CTs exhibited similar capacities to precipitate ALF or BSA, but
      showed small but significant differences in their capacity to precipitate LYS.
      All CTs precipitated ALF more effectively than BSA or LYS. Aggregation of CT
      protein complexes likely aided precipitation of ALF and BSA, but not LYS. This
      study, one of the first to use CTs of confirmed high purity, demonstrates that
      the mDP of CTs influences protein precipitation efficacy.

PMID- 25569854
TI  - Surface modification of sulfur electrodes by chemically anchored cross-linked
      polymer coating for lithium-sulfur batteries.
AB  - Lithium-sulfur batteries suffer from severe self-discharge due to polysulfide
      dissolution into electrolytes. In this work, a chemically anchored polymer-coated
      (CAPC) sulfur electrode was prepared, through chemical bonding by coordinated Cu
      ions and cross-linking, to improve cyclability for Li/S batteries. This electrode
      retained specific capacities greater than 665 mAh g(-1) at high current density
      of 3.35 A g(-1) (2C rate) after 100 cycles with an excellent Coulombic efficiency
      of 100%. 

PMID- 25569851
TI  - Notch Activation of Ca(2+) Signaling in the Development of Hypoxic Pulmonary
      Vasoconstriction and Pulmonary Hypertension.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is an important physiological response
      that optimizes the ventilation/perfusion ratio. Chronic hypoxia causes vascular
      remodeling, which is central to the pathogenesis of hypoxia-induced pulmonary
      hypertension (HPH). We have previously shown that Notch3 is up-regulated in HPH
      and that activation of Notch signaling enhances store-operated Ca(2+) entry
      (SOCE), an important mechanism that contributes to pulmonary arterial smooth
      muscle cell (PASMC) proliferation and contraction. Here, we investigate the role
      of Notch signaling in HPV and hypoxia-induced enhancement of SOCE. We examined
      SOCE in human PASMCs exposed to hypoxia and pulmonary arterial pressure in mice
      using the isolated perfused/ventilated lung method. Wild-type and canonical
      transient receptor potential (TRPC) 6(-/-) mice were exposed to chronic hypoxia
      to induce HPH. Inhibition of Notch signaling with a gamma-secretase inhibitor
      attenuates hypoxia-enhanced SOCE in PASMCs and hypoxia-induced increase in
      pulmonary arterial pressure. Our results demonstrate that hypoxia activates Notch
      signaling and up-regulates TRPC6 channels. Additionally, treatment with a Notch
      ligand can mimic hypoxic responses. Finally, inhibition of TRPC6, either
      pharmacologically or genetically, attenuates HPV, hypoxia-enhanced SOCE, and the
      development of HPH. These results demonstrate that hypoxia-induced activation of
      Notch signaling mediates HPV and the development of HPH via functional activation
      and up-regulation of TRPC6 channels. Understanding the molecular mechanisms that
      regulate cytosolic free Ca(2+) concentration and PASMC proliferation is critical
      to elucidation of the pathogenesis of HPH. Targeting Notch regulation of TRPC6
      will be beneficial in the development of novel therapies for pulmonary
      hypertension associated with hypoxia. 

PMID- 25569855
TI  - Diabetes care entering 2015: ineffective ranting.

PMID- 25569856
TI  - The Relationship of the Fibrinogen Cleavage Biomarker Aalpha-Val360 With Disease
      Severity and Activity in alpha1-Antitrypsin Deficiency.
AB  - BACKGROUND: New markers of COPD and emphysema disease activity are urgently
      required since current measures of disease severity do not reflect the total
      disease burden nor predict disease progression. A recently described in vivo
      marker of neutrophil elastase activity (Aalpha-Val360) may be an effective marker
      of COPD and emphysema disease activity, and the current study explores its use in
      patients with alpha1-antitrypsin deficiency (AATD) across the disease severity
      spectrum with particular interest in whether it can be used as an early predictor
      of the need for intervention. METHODS: Cross-sectional and longitudinal
      relationships between Aalpha-Val360 and full lung-function tests, CT scan
      densitometry, and other biomarkers were explored in this study of a registry of
      untreated patients with PiZZ AATD. RESULTS: The Aalpha-Val360 related cross
      sectionally to physiologic, radiologic, and symptomatic markers of disease
      severity though not disease progression. Similar cross-sectional relationships
      were observed in subjects with mild physiologic abnormalities; however, in this
      subgroup, baseline Aalpha-Val360 concentration did relate to subsequent disease
      progression. CONCLUSIONS: In cross-sectional studies, Aalpha-Val360 reflects
      disease severity in AATD and may be a useful marker of disease activity in
      patients with early disease in whom therapeutic intervention may be indicated.

PMID- 25569857
TI  - Benthic assemblages on artificial reefs in the northwestern Adriatic Sea: does
      structure type and age matter?
AB  - The use of artificial reefs is on the rise worldwide. While their fish
      aggregating effects are well known, the epibenthic assemblages have been poorly
      investigated. Two types of artificial reefs (pyramids of concrete slabs and
      bundles of concrete tubes) have been deployed out of the Po River Delta in 2006
      and 2010. The epibenthic assemblages were investigated in 2009 and 2012. Benthic
      assemblages on both structure typologies were dominated by species tolerating
      high sedimentation rates. Dissimilarities were found among assemblages with
      different ages, and, in less extend, between reef typologies. Colonisation by
      Mytilus galloprovincialis and other major space occupiers did not follow a clear
      succession pattern and was not affected by reef typology. Species colonisation
      was likely driven by variability in environmental conditions and recruitment
      processes rather than by reef typology. This study suggests that environmental
      features of the deployment sites should be carefully considered in planning and
      designing artificial reefs, especially in eutrophic and turbid coastal waters,
      exposed to high river loads. 

PMID- 25569860
TI  - Properties of sparse penalties on inferring gene regulatory networks from time
      course gene expression data.
AB  - Genes regulate each other and form a gene regulatory network (GRN) to realise
      biological functions. Elucidating GRN from experimental data remains a
      challenging problem in systems biology. Numerous techniques have been developed
      and sparse linear regression methods become a promising approach to infer
      accurate GRNs. However, most linear methods are either based on steady-state gene
      expression data or their statistical properties are not analysed. Here, two
      sparse penalties, adaptive least absolute shrinkage and selection operator and
      smoothly clipped absolute deviation, are proposed to infer GRNs from time-course
      gene expression data based on an auto-regressive model and their Oracle
      properties are proved under mild conditions. The effectiveness of those methods
      is demonstrated by applications to in silico and real biological data. 

PMID- 25569859
TI  - Fundamental limitation of the instantaneous approximation in fold-change
      detection models.
AB  - The phenomenon of fold-change detection, or scale-invariance, is exhibited by a
      variety of sensory systems, in both bacterial and eukaryotic signalling pathways.
      It has been often remarked in the systems biology literature that certain systems
      whose output variables respond at a faster time scale than internal components
      give rise to an approximate scale-invariant behaviour, allowing approximate fold
      change detection in stimuli. This study establishes a fundamental limitation of
      such a mechanism, showing that there is a minimal fold-change detection error
      that cannot be overcome, no matter how large the separation of time scales is. To
      illustrate this theoretically predicted limitation, the authors discuss two
      common biomolecular network motifs, an incoherent feedforward loop and a feedback
      system, as well as a published model of the chemotaxis signalling pathway of
      Dictyostelium discoideum. 

PMID- 25569861
TI  - Evolutionary dynamics of morphological stability in a long-term experiment with
      Escherichia coli.
AB  - To investigate the questions in morphological evolution, some biologists seek to
      carry out evolution experiments owing to the incompleteness and uncontrollability
      of the fossil record and natural populations. To quantitatively analyse the
      morphology (cell size) evolution observed from a long-term experiment with
      Escherichia coli, the authors present three mathematical approximations to the
      Wright-Fisher model of the morphological evolution. They firstly use a
      deterministic approximation, which fails to predict evolutionary dynamics of cell
      size and proves the importance of stochasticity in large populations. Then, they
      develop a stochastic approximation and derive an analytic expression for the
      anticipated waiting time to reach the stability of cell size. The results show
      that the calculation of this waiting time is in good agreement with the
      experimental data and that the selective advantage plays a prominent role in cell
      size evolution, with mutation rate and population size having less impact.
      Finally, they employ a multistep process to approximate the Wright-Fisher model
      of cell size evolution and acquire an analytical formula for the median waiting
      time until the stability of cell size. This median time supports the idea that
      the selective advantage is the dominant force for the morphological evolution in
      the long-term experiment. 

PMID- 25569858
TI  - Will Lipidation of ApoA1 through Interaction with ABCA1 at the Intestinal Level
      Affect the Protective Functions of HDL?
AB  - The relationship between levels of high-density lipoprotein cholesterol (HDL-C)
      and cardiovascular (CV) risk is well recognized; however, in recent years, large
      scale phase III studies with HDL-C-raising or -mimicking agents have failed to
      demonstrate a clinical benefit on CV outcomes associated with raising HDL-C,
      casting doubt on the "HDL hypothesis." This article reviews potential reasons for
      the observed negative findings with these pharmaceutical compounds, focusing on
      the paucity of translational models and relevant biomarkers related to HDL
      metabolism that may have confounded understanding of in vivo mechanisms. A unique
      function of HDL is its ability to interact with the ATP-binding cassette
      transporter (ABC) A1 via apolipoprotein (Apo) A1. Only recently, studies have
      shown that this process may be involved in the intestinal uptake of dietary
      sterols and antioxidants (vitamin E, lutein and zeaxanthin) at the basolateral
      surface of enterocytes. This parameter should be assessed for HDL-raising drugs
      in addition to the more documented reverse cholesterol transport (RCT) from
      peripheral tissues to the liver. Indeed, a single mechanism involving the same
      interaction between ApoA1 and ABCA1 may encompass two HDL functions previously
      considered as separate: antioxidant through the intestinal uptake of antioxidants
      and RCT through cholesterol efflux from loaded cells such as macrophages. 

PMID- 25569862
TI  - Multi-scale approach for simulating time-delay biochemical reaction systems.
AB  - This study presents a multi-scale approach for simulating time-delay biochemical
      reaction systems when there are wide ranges of molecular numbers. The authors
      construct a new efficient approach based on partitioning into slow and fast
      subsets in conjunction with predictor-corrector methods. This multi-scale
      approach is shown to be much more efficient than existing methods such as the
      delay stochastic simulation algorithm and the modified next reaction method.
      Numerical testing on several important problems in systems biology confirms the
      accuracy and computational efficiency of this approach. 

PMID- 25569863
TI  - Open access notice for the paper 'Anomalous diffusion and multi fractional
      Brownian motion: simulating molecular crowding and physical obstacles in systems
      biology'.

PMID- 25569864
TI  - Nortriptyline for neuropathic pain in adults.
AB  - BACKGROUND: Antidepressants are widely used to treat chronic neuropathic pain
      (pain due to nerve damage), usually in doses below those at which they exert
      antidepressant effects. An earlier review that included all antidepressants for
      neuropathic pain is being replaced by new reviews of individual drugs examining
      individual neuropathic pain conditions.Nortriptyline is a tricyclic
      antidepressant that is occasionally used for treating neuropathic pain, and is
      recommended in European, UK, and USA guidelines. OBJECTIVES: To assess the
      analgesic efficacy and associated adverse events of nortriptyline for chronic
      neuropathic pain in adults. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from inception to 7
      January 2015, and the reference lists of retrieved papers and other reviews. We
      also searched two clinical trials databases for ongoing or unpublished studies.
      SELECTION CRITERIA: We included randomised, double-blind studies of at least two
      weeks' duration comparing nortriptyline with placebo or another active treatment
      in chronic neuropathic pain. Participants were adults aged 18 years and over. We
      included only full journal publication articles and clinical trial summaries.
      DATA COLLECTION AND ANALYSIS: Two review authors independently extracted efficacy
      and adverse event data, and examined issues of study quality. We considered the
      evidence using three tiers. First tier evidence derived from data meeting current
      best standards and subject to minimal risk of bias (outcome equivalent to
      substantial pain intensity reduction, intention-to-treat analysis without
      imputation for dropouts; at least 200 participants in the comparison, 8 to 12
      weeks' duration, parallel design); second tier evidence from data that failed to
      meet one or more of these criteria and were considered at some risk of bias but
      with adequate numbers in the comparison; and third tier evidence from data
      involving small numbers of participants that was considered very likely to be
      biased or used outcomes of limited clinical utility, or both.We planned to
      calculate risk ratio (RR) and numbers needed to treat for an additional
      beneficial outcome (NNT) and harmful outcome (NNH) using standard methods
      expected by The Cochrane Collaboration. MAIN RESULTS: We included six studies
      treating 310 participants (mean or median age 49 to 64 years) with various
      neuropathic pain conditions. Five studies used a cross-over design, and one used
      a parallel-group design; 272 participants were randomised to treatment with
      nortriptyline, 145 to placebo, 94 to gabapentin, 56 to gabapentin plus
      nortriptyline, 55 to morphine, 55 to morphine plus nortriptyline, 39 to
      chlorimipramine, and 33 to amitriptyline. Treatment periods lasted from three to
      eight weeks. All studies had one or more sources of potential major bias.No study
      provided first or second tier evidence for any outcome. Only one study reported
      our primary outcome of people with at least 50% reduction in pain. There was no
      indication that either nortriptyline or gabapentin was more effective in
      postherpetic neuralgia (very low quality evidence). Two studies reported the
      number of people with at least moderate pain relief, and one reported the number
      who were satisfied with their pain relief and had tolerable adverse effects. We
      considered these outcomes to be equivalent to our other primary outcome of
      Patient Global Impression of Change (PGIC) much or very much improved.We could
      not pool data, but third tier evidence in individual studies indicated similar
      efficacy to other active interventions (gabapentin, morphine, chlorimipramine,
      and amitriptyline), and to placebo in the conditions studied (very low quality
      evidence). Adverse event reporting was inconsistent and fragmented. More
      participants reported adverse events with nortriptyline than with placebo,
      similar numbers with nortriptyline and other antidepressants (amitriptyline and
      chlorimipramine) and gabapentin, and slightly more with morphine (very low
      quality evidence). No study reported any serious adverse events or deaths.
      AUTHORS' CONCLUSIONS: We found little evidence to support the use of
      nortriptyline to treat the neuropathic pain conditions included in this review.
      There were no studies in the treatment of trigeminal neuralgia. The studies were
      methodologically flawed, largely due to small size, and potentially subject to
      major bias. The results of this review do not support the use of nortriptyline as
      a first line treatment. Effective medicines with much greater supportive evidence
      are available, such as duloxetine and pregabalin.

PMID- 25569865
TI  - Quantitative assessment of thyroid-to-background ratio improves the interobserver
      reliability of technetium-99m sestamibi thyroid scintigraphy for investigation of
      amiodarone-induced thyrotoxicosis.
AB  - BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) is caused by excessive
      hormone synthesis and release (AIT I), a destructive thyroiditis (AIT II), or a
      combination of both (AIT Ind). Although no gold-standard diagnostic test is
      available, technetium-99m sestamibi thyroid scintigraphy (99mTc-STS) has been
      previously reported to be an accurate tool for differentiating subtypes with
      important therapeutic implications. However, the information to guide reporting
      of 99mTc-STS is qualitative and highly subjective. This study aims to compare the
      interobserver reliability of 99mTc-STS before and after the use of quantitative
      thyroid-to-background ratios (TBRs) displayed on a time-activity curve for
      differentiation of AIT subtypes. METHODS: A retrospective audit of Nuclear
      Medicine Departments at Royal Melbourne Hospital (Parkville, Victoria, Australia)
      and Cabrini Hospital (Malvern, Victoria, Australia) identified 15 consecutive
      99mTc-STS studies performed for AIT. Four nuclear medicine physicians reported
      the studies according to previously established criteria (series 1). Quantitative
      TBR and estimated 'normal' range TBR were subsequently provided before the
      studies were reordered and reported again (series 2). Interobserver reliability
      was calculated using Fleiss' kappa statistic for each assessment. RESULTS: The
      overall percentage of agreement (PoA) and kappa statistics for use of
      conventional 99mTc-STS for diagnosis of AIT improved from 47 to 80% and from 0.30
      to 0.67 following the use of quantitative TBR displayed on a time-activity curve
      with reference to a normal population. Interobserver reliability improved
      substantially under all diagnostic comparisons, particularly for differentiation
      of either AIT I (PoA 80% to 94%, kappa: 0.48 to 0.84) or AIT Ind (PoA 47% to 82%,
      kappa: -0.05 to 0.51) from other types of AIT. CONCLUSION: Use of quantitative
      TBR improves the interobserver reliability of reporting 99mTc-STS for
      investigation of different types of AIT. There is 'almost perfect' agreement upon
      differentiation of AIT I from AIT II and AIT Ind, with important implications for
      rationalizing the use of corticosteroid therapy. Prospective identification of
      AIT Ind is improved from 'poor' to a 'moderate' level of agreement to facilitate
      rational use of combination therapy at diagnosis.

PMID- 25569866
TI  - Early gated SPECT adenosine myocardial perfusion imaging may influence the
      therapeutic management of patients with coronary artery disease.
AB  - AIM: The aim of the study was to investigate whether myocardial perfusion imaging
      at 15 min after injection (T15) is more accurate in detecting coronary artery
      disease than that at 45 min (T45). PATIENTS AND METHODS: Two-day stress/rest
      99mTc-tetrofosmin gated SPECT was performed at T15 and T45 in 50 patients.
      Coronary angiography was considered when poststress and resting images were
      discordant. Tracer washout rates were calculated for the myocardium, liver, and
      subdiaphragmatic region. Perfusion sum difference scores were derived using QPS
      software. RESULTS: T15 and T45 were discordant in 18/50 (36%) patients. In 16/18
      patients (89%) discordant deficits were more apparent at T15. A total of 13/16
      patients underwent coronary angiography, of whom 12 had coronary artery disease.
      Poststress, but not resting, left ventricular ejection fraction was lower at T15
      (P=0.02). Sum difference scores were higher at T15 [2.2 (1.9)] than at T45 [1.6
      (1.7); P<0.05]. Tracer washout rates from the liver [46 (13.3)%] and
      subdiaphragmatic region [36 (21.3)%] were significant (P<0.0001), but there was
      no change in myocardial activity. CONCLUSION: T15 detected more abnormalities
      than did T45. The reduction in left ventricular ejection fraction after stress
      may result from adenosine-induced poststunning at T15. Accordingly, the T15
      protocol may be useful in the assessment of hibernating myocardium. Contrasting
      myocardial and hepatic washout rates may be attributable to differential ABC
      transporter expression.

PMID- 25569867
TI  - Wrinkles.
AB  - INTRODUCTION: Skin disorders associated with photodamage from ultraviolet light
      include wrinkles, hyperpigmentation, tactile roughness, and telangiectasia, and
      are more common in people with white skin compared with other skin types.
      Wrinkles are also associated with ageing, hormonal status, smoking, and
      intercurrent disease. METHODS AND OUTCOMES: We conducted a systematic review and
      aimed to answer the following clinical question: What are the effects of
      treatments for skin wrinkles? We searched: Medline, Embase, The Cochrane Library,
      and other important databases up to February 2014 (Clinical Evidence reviews are
      updated periodically; please check our website for the most up-to-date version of
      this review). We included harms alerts from relevant organisations such as the US
      Food and Drug Administration (FDA) and the UK Medicines and Healthcare products
      Regulatory Agency (MHRA). RESULTS: We found 33 studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions:
      botulinum toxin injection (e.g., botulinum toxin type A and type B), carbon
      dioxide laser, chemical peel (including alpha and beta hydroxyl acids),
      dermabrasion, isotretinoin, tazarotene, tretinoin, and variable pulse erbium:YAG
      laser.

PMID- 25569868
TI  - Steroids and fluorouracil for keloids and hypertrophic scars.

PMID- 25569870
TI  - Visible assay for glycosylase based on intrinsic catalytic ability of
      graphene/gold nanoparticles hybrids.
AB  - A sensitive, rapid and label-free assay for colorimetric detection of human 8
      hydroxyguanine glycosylase (hOGG1) was proposed based on the tunable catalytic
      ability of graphene/gold nanoparticles (graphene/Au-NPs) hybrids and the terminal
      protection of hOGG1. In presence of H2O2, the hybrids were capable of catalyzing
      the oxidation of color developing reagent, causing a concomitant change in color.
      Due to the excellent controllability, the capacity could be inhibited by
      adsorption of ssDNA onto the hybrids sheets and recovered when the adsorbed ssDNA
      was digested by exonuclease. The terminal protection of hOGG1 could irreversibly
      interrupt the digestion of the captured ssDNA (containing the oxidative damage
      site) by the exonuclease, thus preventing the catalytic ability of graphene/Au
      NPs from being recovered. The original color change which related to the
      concentration of the protected ssDNA facilitated quantitative detection of hOGGl
      activity. Compared with conventional methods for hOGG1 detection, the presented
      assay without any labeling process greatly simplified the operation steps and
      reduced the analysis time. This approach performed a linear response for hOGG1
      activity from 0.02 to 0.11 U/MUL with a detection limit of 0.0016 U/MUL, and
      realized the quantification of hOGG1 activity in real cell lines.

PMID- 25569871
TI  - Label-free electrochemical detection of prostate-specific antigen based on
      nucleic acid aptamer.
AB  - We report a label-free aptasensor to make direct detection of prostate specific
      antigen (PSA, a biomarker of prostate cancer) using a quinone-containing
      conducting copolymer acting as redox transducer and grafting matrix for
      immobilization of the short aptamer strands. It is shown that capture of PSA
      generates a current decrease (signal-off) measured by Square Wave Voltammetry.
      This current decrease is specific for PSA above a limit of quantification in the
      ng mL(-1) range. The change in current is used to determine the PSA-aptamer
      dissociation constant K(D), of ca. 2.6 nM. To consolidate the proof of concept, a
      heterogeneous competitive exchange with a complementary DNA strand which breaks
      PSA-aptamer interactions is studied. This double-check followed by a current
      increase provides full assurance of a perfectly specific recognition.

PMID- 25569869
TI  - Regulating exocytosis of nanoparticles via host-guest chemistry.
AB  - Prolonged retention of internalized nanoparticulate systems inside cells improves
      their efficacy in imaging, drug delivery, and theranostic applications.
      Especially, regulating exocytosis of the nanoparticles is a key factor in the
      fabrication of effective nanocarriers for chemotherapeutic treatments but
      orthogonal control of exocytosis in the cellular environment is a major
      challenge. Herein, we present the first example of regulating exocytosis of gold
      nanoparticles (AuNPs), a model drug carrier, by using a simple host-guest
      supramolecular system. AuNPs featuring quaternary amine head groups were
      internalized into the cells through endocytosis. Subsequent in situ treatment of
      a complementary cucurbit[7]uril (CB[7]) to the amine head groups resulted in the
      AuNP-CB[7] complexation inside cells, rendering particle assembly. This
      complexation induced larger particle assemblies that remained sequestered in the
      endosomes, inhibiting exocytosis of the particles without any observed
      cytotoxicity. 

PMID- 25569872
TI  - Rapid and label-free amplification and detection assay for genotyping of cancer
      biomarker.
AB  - As understanding of the molecular pathways that drive malignancy in human cancer
      improves, personalized genotype-based therapy in combination with the predictive
      biomarker for the efficacy of targeted therapy is becoming more popular in cancer
      management. Sanger sequencing, that has been the gold standard for mutation
      analysis in cancer since the 1970s, suffers from low sensitivity, complexity, and
      time-consuming and labor-intensive procedure. Although several PCR based
      molecular testing methods are being emerged, there is no universal assay
      available for genotyping of cancer biomarkers. Here we present a rapid, simple
      and sensitive assay for the detection of epidermal growth factor receptor (EGFR)
      mutation in non-small cell lung cancers (NSCLCs). The assay employs a novel
      double mis-matched primer (DMP) set to improve the detection ability of
      isothermal solid-phase amplification/detection (ISAD) based on silicon microring
      biosensor. We show that the EGFR-DMP can detect EGFR gene mutations within 20 min
      in a label-free and real-time manner. The EGFR-DMP was able to detect a mutation
      in a sample containing only 1% of the mutant cells in a mixture of wild-type
      cells. Furthermore, to validate the proposed assay for potential applications in
      clinical diagnostics, we examined paraffin-embedded tissue samples from 10 NSCLC
      patients for the presence of EGFR mutations by performing EGFR-DMP and direct
      sequencing. The EGFR-DMP assay was able to rapidly detect the mutation, with high
      sensitivity and specificity. The EGFR-DMP assay offers a robust and sensitive
      approach for the rapid identification of the EGFR mutation. The high sensitivity
      and specificity and rapidity of this approach may make it useful for predicting
      the clinical response to targeted EGFR TKIs as a companion diagnostic.

PMID- 25569873
TI  - Upconversion nanoparticle-based fluorescence resonance energy transfer assay for
      organophosphorus pesticides.
AB  - This paper reports a novel nanosensor for organophosphorus pesticides based on
      the fluorescence resonance energy transfer (FRET) between NaYF4:Yb,Er
      upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs). The detection
      mechanism is based on the facts that AuNPs quench the fluorescence of UCNPs and
      organophosphorus pesticides (OPs) inhibit the activity of acetylcholinesterase
      (AChE) which catalyzes the hydrolysis of acetylthiocholine (ATC) into
      thiocholine. Under the optimized conditions, the logarithm of the pesticides
      concentration was proportional to the inhibition efficiency. The detection limits
      of parathion-methyl, monocrotophos and dimethoate reached 0.67, 23, and 67 ng/L,
      respectively. Meanwhile, the biosensor shows good sensitivity, stability, and
      could be successfully applied to detection of OPs in real food samples,
      suggesting the biosensor has potentially extensive application clinic diagnoses
      assays.

PMID- 25569874
TI  - Au@Ag nanorods based electrochemical immunoassay for immunoglobulin G with signal
      enhancement using carbon nanofibers-polyamidoamine dendrimer nanocomposite.
AB  - Au@Ag nanorods (Au@AgNRs) was utilized to construct a novel sandwich-type
      electrochemical immunosensor for the detection of immunoglobulin G (IgG). The
      sensor was prepared by immoblizing capture antibodies on the amine-terminated
      nanocomposite of carbon nanofibers-polyamidoamine dendrimer (CNFs-PAMAM), whilst
      the trace tag was prepared by loading anti-human IgG on Au@AgNRs. The "built-in"
      Ag layer on Au nanorods was characterized by UV-vis extinction spectra,
      transmission electron microscopy and energy dispersive spectroscopy. The results
      of cyclic voltammetry indicated that modifying CNFs-PAMAM nanocomposite on glassy
      carbon electrode enabled 177 times of peak current increase of Ag in the
      bimetallic nanorods. The peak current was quantitatively related with the
      concentration of the target protein IgG via the formation of immunocomplex. After
      the parameter optimization, the oxidative peak current of silver was proportional
      to the concentration of IgG in a wide linear range of six orders of magnitude
      with a low detection limit of 0.5 fg mL(-1). Besides, this sensor showed
      acceptable reproducibility and stability, and thus the strategy reported here has
      great promise for extension to the other disease biomarkers.

PMID- 25569875
TI  - Poly (9-(2-diallylaminoethyl)adenine HCl-co-sulfur dioxide) deposited on silica
      nanoparticles constructs hierarchically ordered nanocapsules: curcumin conjugated
      nanocapsules as a novel strategy to amplify guanine selectivity among
      nucleobases.
AB  - Poly (9-(2-diallylaminoethyl)adenine HCl-co-sulfur dioxide) (Poly A) deposited on
      silica nanoparticles self-assembles to form hierarchically ordered nanocapsules.
      These nanocapsules can be conjugated with curcumin. The curcumin-conjugated
      nanocapsules are found to be spherical in size and their size ranges between 200
      and 600 nm. We found that curcumin conjugated with silica nanoparticles
      marginally shows a selectivity (~20%) for guanine over adenine, cytosine, thymine
      and uracil, but this selectivity is extraordinarily amplified to more than 500%
      in curcumin-conjugated nanocapsules prepared from the above procedure. FT-IR
      spectra along with lifetime measurements suggest that specific interaction
      between adenine moieties of Poly A nanocapsules and thymine/uracil does not
      affect the fluorescence of poly A nanocapsules. Thus, the sensitivity and
      selectivity for guanine estimation is due to hydrophobic interactions, which are
      assisted by the low water solubility of guanine as compared to the other
      nucleobases. The present method illustrates a wider linear dynamic range in the
      higher concentration range as compared to the reported methods. Finally, the
      degradation study proves that stability of curcumin is improved dramatically in
      such nanocapsules demonstrating that nanotechnology could be a viable method to
      improve selectivity of specific analyte and robustness of probe molecule during
      fluorescence based bio-sensing.

PMID- 25569876
TI  - Imaging of nucleolar RNA in living cells using a highly photostable deep-red
      fluorescent probe.
AB  - A new crescent-shape fluorescent probe (named here as CP) that selectively stains
      RNA in nucleoli of living cells is prepared. CP shows a deep-red emission (658
      nm) and a large Stokes shift because of the introduction of rigid-conjugated
      coumarin moiety into the molecular structure. Cell imaging experiments indicate
      that CP can rapidly stain nucleoli in living cells by binding with nucleolar RNA,
      showing performance superior to commercially available nucleoli dye SYTO
      RNASelect in terms of high photostability and selectivity. More significantly,
      these excellent properties together with low cytotoxicity enable CP to monitor
      nucleolar RNA changes during mitosis, and after treating with anti-cancer drugs
      cisplatin, actinomycin D and alpha-amanitin. Thus, CP could be a potential tool
      for real-time, long-term visualization of the dynamic changes for nucleolar RNA
      and evaluation of the therapeutic effect for anti-cancer drugs that targeted RNA
      polymerase I (Pol I).

PMID- 25569877
TI  - Electrochemistry and electrochemiluminescence from a redox-active metal-organic
      framework.
AB  - The marriage of metal-organic frameworks (MOFs) and electrochemiluminescence
      (ECL) can combine their merits together. Designing ECL-active MOF with a high
      electron transfer capacity and high stability is critical for ECL emission. Here
      we reported the ECL from a redox-active MOF prepared from {Ru[4,4'-(HO2C)2
      bpy]2bpy}(2+) and Zn(2+); a property of MOFs has not been reported previously.
      The MOF structure is independent of its charge and is therefore stable
      electrochemically. The redox-activity and well-ordered porous structure of the
      MOF were confirmed by its electrochemical properties and ECL emission. The high
      ECL emission indicated the ease of electron transfer between the MOF and co
      reactants. Furthermore, the MOF exhibited permselectivity, charge selectivity,
      and catalytic selectivity along with a stable and concentration-dependent ECL
      emission toward co-reactants. ECL mechanism was proposed based on the results.
      The detection and recovery of cocaine in the serum sample was used to validate
      the feasibility of MOF- based ECL system. The information obtained in this study
      provides a better understanding of the redox properties of MOFs and their
      potential electrochemical applications. 

PMID- 25569878
TI  - Simultaneous detection of hydrogen peroxide and glucose in human serum with
      upconversion luminescence.
AB  - In this paper, a green upconversion photoluminescence (UCPL) system for the
      highly sensitive and selective detection of H2O2 and glucose in human sera was
      developed by utilizing the excellent optical properties of NaYF4:Yb(3+)/Er(3+)
      upconversion nanoparticles (UCNPs). In the presence of H2O2, the colorless
      3,3',5,5'-tetramethylbenzidine (TMB) was oxidized into blue oxidized TMB (oxTMB)
      by assistance of horseradish peroxidase (HRP). And the green UCPL of UCNPs was
      quenched by the oxTMB linearly over the range of 100 nM-4.0 MUM with a low limit
      of detection (LOD) of 45.0 nM for H2O2. Based on the transformation of glucose
      into H2O2 by means of glucose oxidase, the TMB-UCNPs-HRP system was further
      exploited for the highly sensitive detection of glucose in the range of 0.1-5.0
      MUM with a LOD of 64.0 nM in human sera independent of preconcentration and
      purification. The results are in good agreement with the clinical data,
      suggesting that this UCPL nanosensor is highly practical.

PMID- 25569879
TI  - Integrated centrifugal reverse transcriptase loop-mediated isothermal
      amplification microdevice for influenza A virus detection.
AB  - An integrated reverse transcriptase loop-mediated isothermal amplification (RT
      LAMP) microdevice which consists of microbead-assisted RNA purification and RT
      LAMP with real-time monitoring by a miniaturized optical detector was
      demonstrated. The integrated RT-LAMP microdevice includes four reservoirs for a
      viral RNA sample (purified influenza A viral RNA or lysates), a washing solution
      (70% ethanol), an elution solution (RNase-free water), and an RT-LAMP cocktail,
      and two chambers (a waste chamber and an RT-LAMP reaction chamber). The separate
      reservoirs for a washing solution, an elution solution, and an RT-LAMP cocktail
      were designed with capillary valves for stable storage. Three influenza A virus
      strains (A/H1N1, A/H3N2, and A/H5N1) were used for RNA templates, and RT-LAMP
      primer sets were designed to detect hemagglutinin (HA) and conserved M gene.
      Sequential sample flow to the microbeads for RNA purification was achieved by
      centrifugal force with optimization of capillary valves and a siphon channel.
      Furthermore, the purified RNA solution was successfully isolated from the waste
      solution by changing the rotational direction, and combined with the RT-LAMP
      cocktail in the RT-LAMP reaction chamber for target gene amplification. Total
      process from the sample injection to the result was completed in 47 min.
      Influenza A H1N1 virus was confirmed on the integrated RT-LAMP microdevice even
      with 10 copies of viral RNAs, which revealed 10-fold higher sensitivity than that
      of a conventional RT-PCR. Subtyping and specificity test of influenza A H1N1
      viral lysates were also performed and clinical samples were successfully
      genotyped to confirm influenza A virus on our proposed integrated microdevice.

PMID- 25569880
TI  - The minimal clinically important difference of the Control of Allergic Rhinitis
      and Asthma Test (CARAT): cross-cultural validation and relation with pollen
      counts.
AB  - BACKGROUND: The Control of Allergic Rhinitis and Asthma Test (CARAT) monitors
      control of asthma and allergic rhinitis. AIMS: To determine the CARAT's minimal
      clinically important difference (MCID) and to evaluate the psychometric
      properties of the Dutch CARAT. METHODS: CARAT was applied in three measurements
      at 1-month intervals. Patients diagnosed with asthma and/or rhinitis were
      approached. MCID was evaluated using Global Rating of Change (GRC) and standard
      error of measurement (s.e.m.). Cronbach's alpha was used to evaluate internal
      consistency. Spearman's correlation coefficients were calculated between CARAT,
      the Asthma Control Questionnaire (ACQ5) and the Visual Analog Scale (VAS) on
      airway symptoms to determine construct and longitudinal validity. Test-retest
      reliability was evaluated with intra-class correlation coefficient (ICC). Changes
      in pollen counts were compared with delta CARAT and ACQ5 scores. RESULTS: A total
      of 92 patients were included. The MCID of the CARAT was 3.50 based on GRC scores;
      the s.e.m. was 2.83. Cronbach's alpha was 0.82. Correlation coefficients between
      CARAT and ACQ5 and VAS questions ranged from 0.64 to 0.76 (P < 0.01).
      Longitudinally, correlation coefficients between delta CARAT scores and delta
      ACQ5 and VAS scores ranged from 0.41 to 0.67 (P < 0.01). Test-retest reliability
      showed an ICC of 0.81 (P < 0.01) and 0.80 (P < 0.01). Correlations with pollen
      counts were higher for CARAT than for ACQ5. CONCLUSIONS: This is the first
      investigation of the MCID of the CARAT. The CARAT uses a whole-point scale, which
      suggests that the MCID is 4 points. The CARAT is a valid and reliable tool that
      is also applicable in the Dutch population.

PMID- 25569881
TI  - Using support vector machines to identify protein phosphorylation sites in
      viruses.
AB  - Phosphorylation of viral proteins plays important roles in enhancing replication
      and inhibition of normal host-cell functions. Given its importance in biology, a
      unique opportunity has arisen to identify viral protein phosphorylation sites.
      However, experimental methods for identifying phosphorylation sites are resource
      intensive. Hence, there is significant interest in developing computational
      methods for reliable prediction of viral phosphorylation sites from amino acid
      sequences. In this study, a new method based on support vector machine is
      proposed to identify protein phosphorylation sites in viruses. We apply an
      encoding scheme based on attribute grouping and position weight amino acid
      composition to extract physicochemical properties and sequence information of
      viral proteins around phosphorylation sites. By 10-fold cross-validation, the
      prediction accuracies for phosphoserine, phosphothreonine and phosphotyrosine
      with window size of 23 are 88.8%, 95.2% and 97.1%, respectively. Furthermore,
      compared with the existing methods of Musite and MDD-clustered HMMs, the high
      sensitivity and accuracy of our presented method demonstrate the predictive
      effectiveness of the identified phosphorylation sites for viral proteins. 

PMID- 25569882
TI  - Unsupervised discrimination of motor unit action potentials using spectrograms.
AB  - Single motor unit activity study is a major research interest because changes of
      MUAP morphology, MU activation, and MU recruitment provide the most informative
      part in diagnosis and treatment of neuromuscular disorders. Intramuscular
      recordings often provide a more than one motor unit activities, thus MUAP
      discrimination is a crucial task to study single unit activities. Most neurology
      laboratories worldwide still need specialists who spend hours to classify MUAPs.
      In this study, we present a new real-time unsupervised method for MUAP
      discrimination. After automatically detect MUAPs, we extract features of
      spectrogram images from the wavelet coefficients of MUAPs. Unlike benchmark
      methods, we do not calculate Euclidean distances which assumes a spherical
      distribution of data. Instead, we measure correlation between spectrogram images.
      Then MUAPs are automatically discriminated without any prior knowledge of the
      number of clusters as in previous works. MUAP were detected on a real data set
      with a precision PPV of 94% (tolerance of 2 ms). We obtained a similar result in
      MUAP classification to the reference. The difference in percentages of MU
      proportions between our method and the reference were 3% for MU1, 0.4% for MU2,
      and 12% for MU3. In contrast, F1-score for MU3 reached the highest level at 91%
      (PPV at the highest of 96.64% as well). 

PMID- 25569883
TI  - Motion discrimination technique by EMG signals using hyper-sphere model.
AB  - This study developed a method of discriminating real-time motion from
      electromyogram (EMG) signals. We previously proposed a real-time motion
      discrimination method using hyper-sphere models that discriminated five motions
      (open, grasp, pinching, wrist extension, and wrist flexion) above 90% and quickly
      learned EMG signals. Our method prevents elbow motions from interfering with hand
      motion discrimination. However, we presume in our method that feature quantities
      do not change with time. Discrimination accuracy might deteriorate over time.
      Additionally, our method only discriminated three motions (open, grasp, pinching)
      for finger motions. This paper proposes the effectiveness of our method for
      changing feature quantities caused by time variation and a real-time motion
      discrimination method using new hyper-sphere models for four finger motions
      (open, grasp, pinching, and 2-5th finger flexion). We carried out two experiments
      and verified the effectiveness of our method for changing feature quantities and
      four finger motions discrimination using the new hyper-sphere models. 

PMID- 25569884
TI  - Human motion segmentation by data point classification.
AB  - Contemporary physiotherapy and rehabilitation practice uses subjective measures
      for motion evaluation and requires time-consuming supervision. Algorithms that
      can accurately segment patient movement would provide valuable data for progress
      tracking and on-line patient feedback. In this paper, we propose a two-class
      classifier approach to label each data point in the patient movement data as
      either a segment point or a non-segment point. The proposed technique was applied
      to 20 healthy subjects performing lower body rehabilitation exercises, and
      achieves a segmentation accuracy of 82%. 

PMID- 25569885
TI  - Boosting training for myoelectric pattern recognition using Mixed-LDA.
AB  - Pattern recognition based myoelectric prostheses (MP) need a training procedure
      for calibrating the classifier. Due to the non-stationarity inhered in surface
      electromyography (sEMG) signals, the system should be retrained day by day in
      long-term use of MP. To boost the training procedure in later periods, we propose
      a method, namely Mixed-LDA, which computes the parameters of LDA through
      combining the model estimated on the incoming training samples of the current day
      with the prior models available from earlier days. An experiment ranged for 10
      days on 5 subjects was carried out to simulate the long-term use of MP. Results
      show that the Mixed-LDA is significantly better than the baseline method (LDA)
      when few samples are used as training set in the new (current) day. For instance,
      in the task including 13 hand and wrist motions, the average classification rate
      of the Mixed-LDA is 88.74% when the number of training samples is 104 (LDA:
      79.32%). This implies that the approach has the potential to improve the
      usability of MP based on pattern recognition by reducing the training time. 

PMID- 25569886
TI  - Using surface electromyography (SEMG) to classify low back pain based on lifting
      capacity evaluation with principal component analysis neural network method.
AB  - Low back pain (LBP) is a leading cause of disability. The population with low
      back pain is continuously growing in the recent years. This study tries to
      distinguish LBP patients with healthy subjects by using the objective surface
      electromyography (SEMG) as a quantitative score for clinical evaluations. There
      are 26 healthy and 26 low back pain subjects who involved in this research. They
      lifted different weights by static and dynamic lifting process. Multiple features
      are extracted from the raw SEMG data, including energy and frequency indexes.
      Moreover, false discovery rate (FDR) omitted the false positive features. Then, a
      principal component analysis neural network (PCANN) was used for classifications.
      The results showed the features with different loadings (including 30%, and 50%
      loading) on lifting which can be used for distinguishing healthy and back pain
      subjects. By using PCANN method, more than 80% accuracies are achieved when
      different lifting weights were applied. Moreover, it is correlated between some
      EMG features and clinical scales, on exertion, fatigue, and pain. This technology
      can be potentially used for the future researches as a computer-aid diagnosis
      tool of LBP evaluation. 

PMID- 25569887
TI  - Comparison between wire and wireless EEG acquisition systems based on SSVEP in an
      Independent-BCI.
AB  - This paper presents a comparison between two different technologies of
      acquisition systems (BrainNet36 and Emotiv Epoc) for an Independent-BCI based on
      Steady-State Visual Evoked Potential (SSVEP). Two stimuli separated by a viewing
      angle <; 1 degrees  were used. Multivariate Synchronization Index (MSI) technique
      was used as feature extractor and five subjects participated in the experiments.
      The class is obtained through a criterion of maxima. The left and right flicker
      stimuli were modulated at frequencies of 8.0 and 13.0 Hz, respectively.
      Acquisition via BrainNet system showed better results, obtaining the highest
      value for accuracy (100%) and the highest ITR (35.18 bits/min). This Independent
      BCI is based on covert attention. 

PMID- 25569888
TI  - Multi-class ERP-based BCI data analysis using a discriminant space self
      organizing map.
AB  - Emotional or non-emotional image stimulus is recently applied to event-related
      potential (ERP) based brain computer interfaces (BCI). Though the classification
      performance is over 80% in a single trial, a discrimination between those ERPs
      has not been considered. In this research we tried to clarify the
      discriminability of four-class ERP-based BCI target data elicited by desk, seal,
      spider images and letter intensifications. A conventional self organizing map
      (SOM) and newly proposed discriminant space SOM (ds-SOM) were applied, then the
      discriminabilites were visualized. We also classify all pairs of those ERPs by
      stepwise linear discriminant analysis (SWLDA) and verify the visualization of
      discriminabilities. As a result, the ds-SOM showed understandable visualization
      of the data with a shorter computational time than the traditional SOM. We also
      confirmed the clear boundary between the letter cluster and the other clusters.
      The result was coherent with the classification performances by SWLDA. The method
      might be helpful not only for developing a new BCI paradigm, but also for the big
      data analysis. 

PMID- 25569889
TI  - The effect of window size and lead time on pre-impact fall detection accuracy
      using support vector machine analysis of waist mounted inertial sensor data.
AB  - Falls are a major cause of death and morbidity in older adults. In recent years
      many researchers have examined the role of wearable inertial sensors
      (accelerometers and/or gyroscopes) to automatically detect falls. The primary
      goal of such fall monitors is to alert care providers of the fall event, who can
      then commence earlier treatment. Although such fall detection systems may reduce
      time until the arrival of medical assistance, they cannot help to prevent or
      reduce the severity of traumatic injury caused by the fall. In the current study,
      we extend the application of wearable inertial sensors beyond post-impact fall
      detection, by developing and evaluating the accuracy of a sensor system for
      detecting falls prior to the fall impact. We used support vector machine (SVM)
      analysis to classify 7 fall and 8 non-fall events. In particular, we focused on
      the effect of data window size and lead time on the accuracy of our pre-impact
      fall detection system using signals from a single waist sensor. We found that our
      system was able to detect fall events at between 0.0625-0.1875 s prior to the
      impact with at least 95% sensitivity and at least 90% specificity for window
      sizes between 0.125-1 s. 

PMID- 25569890
TI  - Noise tolerant QRS detection using template matching with short-term
      autocorrelation.
AB  - This paper describes a robust method for heart beat detection from noisy
      electrocardiogram (ECG) signals. Generally, the QRS-complex of heart beat is
      extracted from the ECG using a threshold. However, in a noisy condition such a
      mobile and wearable bio-signal monitoring system, noise increases the incidence
      of misdetection and false detection of QRS-complex. To prevent incorrect
      detection, we introduce a novel template matching algorithm. The template
      waveform can be generated autonomously using a short-term autocorrelation method,
      which leverages the similarity of QRS-complex waveforms. Simulation results show
      the proposed method achieves state-of-the-art noise tolerance of heart beat
      detection. 

PMID- 25569891
TI  - Long and short term QT-RR interval co-variability in type 2 diabetes.
AB  - This paper examines the long and short term co-variability of QT and RR intervals
      for diabetic patients to explore if the QT-RR co-variability could yield a noble
      index for the stratification of clinical severity of the disease. Twenty four
      hour Holter ECG recordings are made for 19 type 2 diabetic (T2DM) patients and 25
      normal subjects. RR and QT intervals are extracted from ECG signals sampled at
      200 Hz and their co-variability has been examined. To see the long term QT-RR co
      variability, correlation coefficients and mutual entropies between QT and RR
      intervals have been estimated for original beat to beat intervals and smoothed
      median interval series of successive one hundred beats. Mutual entropy for both
      beat-to-beat and smoothed median QT and RR interval series showed statistically
      significant differences between T2DM and control subjects whereas differences in
      correlation coefficients showed significant difference only for beat-to-beat
      intervals. Mutual entropy between both beat-to-beat and smoothed median QT-RR
      interval sequences showed the equally well separation between T2DM patients and
      control subjects: Mutual entropy and serial correlation coefficients for beat to
      beat intervals are respectively 1.42 +/- 0.33 (bits), 0.856 +/- 0.055 for control
      and 0.752 +/- 0.23 (bits), 0.756 +/- 0.10 for T2DM patients. Scatter diagram
      between RR and QT intervals show apparent nonlinearity which validate this
      result. Short term QT-RR co-variability has been examined by spline smoothed QTc
      series and sporadic changes have been observed for the control subjects whereas
      no such changes are found in diabetic patients. This new phenomenon could be a
      mean for the clinical characterization of diabetes. 

PMID- 25569892
TI  - Subband higher-order statistics and cross-correlation for heartbeat type
      recognition based on two-lead electrocardiogram.
AB  - Regular electrocardiogram beat classification system usually based on single lead
      ECG signal. This study designated to add a second lead of ECG signal to the
      system and apply higher-order statistics and inter-lead cross-correlation
      features to study the influence of the second lead to the recognition rates and
      noise-tolerance of the classifier. Discrete wavelet transformation is employed to
      decompose the ECG signals into different subband components and higher order
      statistics is recruited to characterize the ECG signals as an attempt to elevate
      the accuracy and noise-resistibility of heartbeat discrimination. A feed-forward
      back-propagation neural network (FFBNN) is employed as classifier. When compared
      with the system that uses only one lead, the second lead raises the recognition
      rate from 97.74% to 98.25%. We also study the ability of the two-lead system in
      resisting different levels of white Gaussian noise. More than 97.8% accuracy can
      be retained with the two-lead system even when the SNR decreases to 10 dB. 

PMID- 25569893
TI  - A three class treatment of the FHR classification problem using latent class
      analysis labeling.
AB  - Electronic Fetal Monitoring in the form of cardiotocography is routinely used for
      fetal assessment both during pregnancy and delivery. However its interpretation
      requires a high level of expertise and even then the assessment is somewhat
      subjective as it has been proven by the high inter and intra-observer
      variability. Therefore the scientific community seeks for more objective methods
      for its interpretation. Along this path, presented work proposes a classification
      approach, which is based on a latent class analysis method that attempts to
      produce more objective labeling of the training cases, a step which is vital in a
      classification problem. The method is combined with a simple logistic regression
      approach under two different schemes: a standard multi-class classification
      formulation and an ordinal classification one. The results are promising
      suggesting that more effort should be put in this proposed approach. 

PMID- 25569894
TI  - Automatic detection of overnight deep sleep based on heart rate variability: a
      preliminary study.
AB  - This preliminary study investigated the use of cardiac information or more
      specifically, heart rate variability (HRV), for automatic deep sleep detection
      throughout the night. The HRV data can be derived from cardiac signals, which
      were obtained from polysomnography (PSG) recordings. In total 42 features were
      extracted from the HRV data of 15 single-night PSG recordings (from 15 healthy
      subjects) for each 30-s epoch, used to perform epoch-by-epoch classification of
      deep sleep and non-deep sleep (including wake state and all the other sleep
      stages except deep sleep). To reduce variation of cardiac physiology between
      subjects, we normalized each feature per subject using a simple Z-score
      normalization method by subtracting the mean and dividing by the standard
      deviation of the feature values. A correlation-based feature selection (CFS)
      method was employed to select informative features as well as removing feature
      redundancy and a linear discriminant (LD) classifier was applied for deep and non
      deep sleep classification. Results show that the use of Z-score normalization can
      significantly improve the classification performance. A Cohen's Kappa coefficient
      of 0.42 and an overall accuracy of 81.3% based on a leave-one-subject-out cross
      validation were achieved. 

PMID- 25569895
TI  - Developing an atrial activity-based algorithm for detection of atrial
      fibrillation.
AB  - In this study we propose a novel atrial activity-based method for atrial
      fibrillation (AF) identification that detects the absence of normal sinus rhythm
      (SR) P-waves from the surface ECG. The proposed algorithm extracts nine features
      from P-waves during SR and develops a statistical model to describe the
      distribution of the features. The Expectation-Maximization algorithm is applied
      to a training set to create a multivariate Gaussian Mixture Model (GMM) of the
      feature space. This model is used to identify P-wave absence (PWA) and, in turn,
      AF. An optional post-processing stage, which takes a majority vote of successive
      outputs, is applied to improve classier performance. The algorithm was tested on
      20 records in the MIT-BIH Atrial Fibrillation Database. Classification combining
      seven beats showed a sensitivity of 99.28%, a specificity of 90.21%. The
      presented algorithm has a classification performance comparable to current
      Heartrate-based algorithms yet is rate-independent and capable of making an AF
      determination in a few beats. 

PMID- 25569896
TI  - Fuzzy entropy based motion artifact detection and pulse rate estimation for
      fingertip photoplethysmography.
AB  - The paper presents a fingertip photoplethysmography (PPG) based technique to
      estimate the pulse rate of the subject. The PPG signal obtained from a pulse
      oximeter is used for the analysis. The input samples are corrupted with motion
      artifacts due to minor motion of the subjects. Entropy measure of the input
      samples is used to detect the motion artifacts and estimate the pulse rate. A
      three step methodology is adapted to identify and classify signal peaks as true
      systolic peaks or artifact. CapnoBase database and CSL Benchmark database are
      used to analyze the technique and pulse rate estimation was performed with
      positive predictive value and sensitivity figures of 99.84% and 99.32%
      respectively for CapnoBase and 98.83% and 98.84% for CSL database respectively. 

PMID- 25569897
TI  - Preliminary study for localizing c, d and e waves in photoplethysmogram signals.
AB  - An efficient and robust method based on two moving-average filters followed by a
      dynamic event-duration threshold was developed to locate c, d and e waves in the
      acceleration photoplethysmogram (APG) signals. This investigation was the first
      of its kind to locate c, d and e waves in subjects measured at rest and after
      exercise. The method detects c, d and e in arrhythmia APG signals that suffer
      from: 1) non-stationary effects and 2) low signal-to-noise ratios. The
      performance of the proposed method was tested on 27 records collected in normal
      and heat-stressed conditions, resulting in a 99.95% sensitivity and 98.35%
      positive predictivity. 

PMID- 25569898
TI  - Determination of locations on a tactile sensor suitable for respiration and
      heartbeat measurement of a person on a bed.
AB  - Sleep monitoring systems that can be used in daily life for the assessment of
      personal health and early detection of diseases are needed. To this end, we are
      developing a system for unconstrained measurement of the lying posture,
      respiration and heartbeat of a person on a soft rubber-based tactile sensor
      sheet. The respiration and heartbeat signals can be detected from only particular
      locations on the tactile sensor, and the locations depend on the lying location
      and posture of the measured person. In this paper, we describe how to determine
      the measurement locations on the sensor. We also report a realtime program that
      detects the respiration rate and the heart rate by using this method. 

PMID- 25569899
TI  - Classification of healthy subjects and patients with pulmonary emphysema using
      continuous respiratory sounds.
AB  - In this paper, we propose a new method for classifying patients with pulmonary
      emphysema and healthy subjects using lung sounds. Using conventional
      classification methods, every boundary between inspiratory and expiratory phases
      in successive respiratory sounds are detected manually prior to automatic
      classification. However, manual segmentation must be performed accurately and has
      therefore created significant obstacles in achieving automatic classification. In
      our proposed method, adequate boundaries are detected automatically in the
      classification process, based on the criterion of maximizing the difference
      between the acoustic likelihoods for a candidate with abnormal respiration and
      one with normal respiration. The proposed method achieved a classification rate
      of 83.9% between healthy subjects and patients. The reported rate was 1.3%
      greater than the rate achieved using the conventional method, which required
      manual phase-wise segmentation. Furthermore, the resulting rate was 2.2% higher
      than the rate obtained by the classification in which a lung sound sample was
      divided into phases of equal duration, indicating the effectiveness of the
      proposed method. 

PMID- 25569900
TI  - Evaluation of lower limb vein biomechanical properties and the effects of
      compression stockings, with an instrumented ultrasound probe.
AB  - We present a new approach for the evaluation of the biomechanical properties of
      lower limb veins based on the simultaneous measurements of the vein cross
      sectional area with B-mode ultrasound imaging and of the force exerted on the
      skin by the ultrasound probe. Ongoing clinical trials allowed us to identify a
      behavioral model of lower limb veins without and with compression stockings. 

PMID- 25569901
TI  - Power index of the inspiratory flow signal as a predictor of weaning in intensive
      care units.
AB  - Disconnection from mechanical ventilation, called the weaning process, is an
      additional difficulty in the management of patients in intensive care units
      (ICU). Unnecessary delays in the discontinuation process and a weaning trial that
      is undertaken too early are undesirable. In this study, we propose an extubation
      index based on the power of the respiratory flow signal (Pi). A total of 132
      patients on weaning trials were studied: 94 patients with successful trials
      (group S) and 38 patients who failed to maintain spontaneous breathing and were
      reconnected (group F). The respiratory flow signals were processed considering
      the following three stages: a) zero crossing detection of the inspiratory phase,
      b) inflection point detection of the flow curve during the inspiratory phase, and
      c) calculation of the signal power on the time instant indicated by the
      inflection point. The zero crossing detection was performed using an algorithm
      based on thresholds. The inflection points were marked considering the zero
      crossing of the second derivative. Finally, the inspiratory power was calculated
      from the energy contained over the finite time interval (between the instant of
      zero crossing and the inflection point). The performance of this parameter was
      evaluated using the following classifiers: logistic regression, linear
      discriminant analysis, the classification and regression tree, Naive Bayes, and
      the support vector machine. The best results were obtained using the Bayesian
      classifier, which had an accuracy, sensitivity and specificity of 87%, 90% and
      81% respectively. 

PMID- 25569902
TI  - An adapting system for heartbeat classification minimising user input.
AB  - An adaptive system for the processing of the electrocardiogram (ECG) for the
      classification of heartbeats into beat classes that seeks to minimize the
      required input from the user is presented. A first set of beat annotations is
      produced by the system by processing an incoming recording with a global
      classifier. The beat annotations are then ranked by a confidence measure
      calculated from the posterior probabilities estimates associated with each beat
      classification. An expert then validates and if necessary corrects a fraction of
      the least confident beats of the recording. The system then adapts by first
      training a local-classifier using the newly annotated beats and combines this
      with the global-classifier to produce an adapted classification system. The
      adapted system is then used to update beat annotations. Our results show that we
      can achieve a significant boost in classification performance of the system by
      using a small number of beats for adaptation. 

PMID- 25569903
TI  - A bio-inspired spatial patterning circuit.
AB  - Lateral Inhibition (LI) is a widely conserved patterning mechanism in biological
      systems across species. Distinct from better-known Turing patterns, LI depend on
      cell-cell contact rather than diffusion. We built an in silico genetic circuit
      model to analyze the dynamic properties of LI. The model revealed that LI
      amplifies differences between neighboring cells to push them into opposite
      states, hence forming stable 2-D patterns. Inspired by this insight, we designed
      and implemented an electronic circuit that recapitulates LI patterning dynamics.
      This biomimetic system serve as a physical model to elucidate the design
      principle of generating robust patterning through spatial feedback, regardless of
      the underlying devices being biological or electrical. 

PMID- 25569904
TI  - Adaptive technique for P and T wave delineation in electrocardiogram signals.
AB  - The T and P waves of electrocardiogram signals are excellent indicators in the
      analysis and interpretation of cardiac arrhythmia. As such, the need to address
      and develop an accurate delineation technique for the detection of these waves is
      necessary. In this paper, we present a novel robust and adaptive T and P wave
      delineation method for real-time analysis and nonstandard ECG morphologies. The
      proposed method is based on ECG signal filtering, value estimation of different
      fiducial points, applying backward and forward search windows as well as adaptive
      thresholds. Simulations and evaluations prove the accuracy of the proposed
      technique in comparison to those proposed techniques in the literature. The mean
      error for the T peak, T offset, P peak and P offset values are found to be 9.8,
      2.3, 7.3 and 3.5 milliseconds, respectively, based on the Physionet QT database,
      rendering our algorithm as an excellent candidate for ECG signal analysis. 

PMID- 25569905
TI  - QRS detection by lifting scheme constructing multi-resolution morphological
      decomposition.
AB  - QRS complex detecting algorithm is core of ECG auto-diagnosis method and deeply
      influences cardiac cycle division for signal compression. However, ECG signals
      collected by noninvasive surface electrodes areusually mixed with several kinds
      of interference, and its waveform variation is the main reason for the hard
      realization of ECG processing. This paper proposes a QRS complex detecting
      algorithm based on multi-resolution mathematical morphological decomposition.
      This algorithm possesses superiorities in R peak detection of both mathematical
      morphological method and multi-resolution decomposition. Moreover, a lifting
      constructing method with Maximizationupdating operator is adopted to further
      improve the algorithm performance. And an efficient R peak search-back algorithm
      is employed to reduce the false positives (FP) and false negatives (FN). The
      proposed algorithm provides a good performance applying to MIT-BIH Arrhythmia
      Database, and achieves over 99% detection rate, sensitivity and positive
      predictivity, respectively, and calculation burden is low. Therefore, the
      proposed method is appropriate for portable medical devices in Telemedicine
      system. 

PMID- 25569906
TI  - Fast clustering algorithm for large ECG data sets based on CS theory in
      combination with PCA and K-NN methods.
AB  - Long-term recording of Electrocardiogram (ECG) signals plays an important role in
      health care systems for diagnostic and treatment purposes of heart diseases.
      Clustering and classification of collecting data are essential parts for
      detecting concealed information of P-QRS-T waves in the long-term ECG recording.
      Currently used algorithms do have their share of drawbacks: 1) clustering and
      classification cannot be done in real time; 2) they suffer from huge energy
      consumption and load of sampling. These drawbacks motivated us in developing
      novel optimized clustering algorithm which could easily scan large ECG datasets
      for establishing low power long-term ECG recording. In this paper, we present an
      advanced K-means clustering algorithm based on Compressed Sensing (CS) theory as
      a random sampling procedure. Then, two dimensionality reduction methods:
      Principal Component Analysis (PCA) and Linear Correlation Coefficient (LCC)
      followed by sorting the data using the K-Nearest Neighbours (K-NN) and
      Probabilistic Neural Network (PNN) classifiers are applied to the proposed
      algorithm. We show our algorithm based on PCA features in combination with K-NN
      classifier shows better performance than other methods. The proposed algorithm
      outperforms existing algorithms by increasing 11% classification accuracy. In
      addition, the proposed algorithm illustrates classification accuracy for K-NN and
      PNN classifiers, and a Receiver Operating Characteristics (ROC) area of 99.98%,
      99.83%, and 99.75% respectively. 

PMID- 25569907
TI  - An analytical model for regular respiratory signal.
AB  - In disaster rescue, breathing motion detection is an important approach to
      searching survivors trapped under debris. Detection of breathing motion is
      realized by detecting the respiratory signal acquired by the sensing system. In
      this paper, modeling the regular respiratory signal is studied. Firstly, a
      preliminary model is built based on power of absolute value of cosine function.
      Then, this preliminary model is improved in terms of some practical
      considerations, such as the DC-component of the respiratory signal often is
      removed by signal processing, and a phase uncertainty occurs due to the data
      acquisition. Finally, an analytical harmonic-based random respiratory signal
      model is derived, which can be used as the signal model in the future research
      about breathing motion detection. 

PMID- 25569908
TI  - A model for generating Surface EMG signal of m. Tibialis Anterior.
AB  - A model that simulates surface electromyogram (sEMG) signal of m. Tibialis
      Anterior has been developed and tested. This has a firing rate equation that is
      based on experimental findings. It also has a recruitment threshold that is based
      on observed statistical distribution. Importantly, it has considered both, slow
      and fast type which has been distinguished based on their conduction velocity.
      This model has assumed that the deeper unipennate half of the muscle does not
      contribute significantly to the potential induced on the surface of the muscle
      and has approximated the muscle to have parallel structure. The model was
      validated by comparing the simulated and the experimental sEMG signal recordings.
      Experiments were conducted on eight subjects who performed isometric dorsiflexion
      at 10, 20, 30, 50, 75, and 100% maximal voluntary contraction. Normalized root
      mean square and median frequency of the experimental and simulated EMG signal
      were computed and the slopes of the linearity with the force were statistically
      analyzed. The gradients were found to be similar (p>0.05) for both experimental
      and simulated sEMG signal, validating the proposed model. 

PMID- 25569909
TI  - Verification of the muscle fatigue detection capability of a unipolar-leads
      system using a surface electromyogram model.
AB  - In this study, the muscle fatigue detection capability of bipolar and unipolar
      lead systems used for surface electromyogram measurement was verified by
      simulation. The constructed model simplified the isometric contraction of the
      biceps brachii. There were two simulation experiments: 1) the addition and
      deletion of white noise and 2) the addition and deletion of hum noise. The
      pattern result of simulation 1) suggested the possibility that the muscle fatigue
      detection capability of a unipolar-leads system was high. The pattern 2) result
      showed the unipolar-leads system had a small influence of filtering, and
      suggested that the mixing of hum noise could be disregarded. 

PMID- 25569910
TI  - Optimal autoregressive orders for myopathic electromyograms.
AB  - This paper aims to describe the optimal autoregressive order of varying-length
      electromyograms for myopathic subjects. Epochs of electromyography signals are
      modeled as outputs of autoregressive systems, for orders varying from 1 to 100.
      The optimal order to represent each epoch is chosen by the minimum description
      length criterion. Probability density functions are fitted to the histograms of
      the optimal orders. The lognormal function provides the best fitting, and its
      mean value varies linearly with the epoch length. 

PMID- 25569911
TI  - A novel stimulation for multi-class SSVEP-based brain-computer interface using
      patterns of time-varying frequencies.
AB  - Steady-state visual evoked potential (SSVEP) has become one of the most widely
      employed modalities in online brain computer interface (BCI) because of its high
      signal-to-noise ratio. However, due to the limitations of brain physiology and
      the refresh rate of the display devices, the available stimulation frequencies
      that evoke strong SSVEPs are generally limited for practical applications. In
      this paper, we introduce a novel stimulation method using patterns of time
      varying frequencies that can increase the number of visual stimuli with a fixed
      number of stimulation frequencies for use in multi-class SSVEP-based BCI systems.
      We then propose a probabilistic framework and investigate three approaches to
      detect different patterns of time-varying frequencies. The results confirmed that
      our proposed stimulation is a promising method for multi-class SSVEP-based BCI
      tasks. Our pattern detection approaches improved the detection performance
      significantly by extracting higher quality discriminative information from the
      input signal. 

PMID- 25569912
TI  - Normalizing videos of anterior eye segment surgeries.
AB  - Anterior eye segment surgeries are usually video-recorded. If we are able to
      efficiently analyze surgical videos in real-time, new decision support tools will
      emerge. The main anatomical landmarks in these videos are the pupil boundaries
      and the limbus, but segmenting them is challenging due to the variety of colors
      and textures in the pupil, the iris, the sclera and the lids. In this paper, we
      present a solution to reliably normalize the center and the scale in videos,
      without explicitly segmenting these landmarks. First, a robust solution to track
      the pupil center is presented: it uses the fact that the pupil boundaries, the
      limbus and the sclera / lid interface are concentric. Second, a solution to
      estimate the zoom level is presented: it relies on the illumination pattern
      reflected on the cornea. The proposed solution was assessed in a dataset of 186
      real-live cataract surgery videos. The distance between the true and estimated
      pupil centers was equal to 8.0 +/- 6.9% of the limbus radius. The correlation
      between the estimated zoom level and the true limbus size in images was high: R =
      0.834. 

PMID- 25569913
TI  - Improved automated optic cup segmentation based on detection of blood vessel
      bends in retinal fundus images.
AB  - Glaucoma is a leading cause of permanent blindness. Retinal imaging is useful for
      early detection of glaucoma. In order to evaluate the presence of glaucoma,
      ophthalmologists may determine the cup and disc areas and diagnose glaucoma using
      a vertical optic cup-to-disc (C/D) ratio and a rim-to-disc (R/D) ratio.
      Previously we proposed a method to determine cup edge by analyzing a vertical
      profile of pixel values, but this method provided a cup edge smaller than that of
      an ophthalmologist. This paper describes an improved method using the locations
      of the blood vessel bends. The blood vessels were detected by a concentration
      feature determined from the density gradient. The blood vessel bends were
      detected by tracking the blood vessels from the disc edge to the primary cup
      edge, which was determined by our previous method. Lastly, the vertical C/D ratio
      and the R/D ratio were calculated. Using forty-four images, including 32 glaucoma
      images, the AUCs of both the vertical C/D ratio and R/D ratio by this proposed
      method were 0.966 and 0.936, respectively. 

PMID- 25569914
TI  - Detection of exudates in fundus images using a Markovian segmentation model.
AB  - Diabetic retinopathy (DR) is one of the most common causing of vision loss in
      developed countries. In early stage of DR, some signs like exudates appear in the
      retinal images. An automatic screening system must be capable to detect these
      signs properly so that the treatment of the patients may begin in time. The
      appearance of exudates shows a rich variety regarding their shape and size making
      automatic detection more challenging. We propose a way for the automatic
      segmentation of exudates consisting of a candidate extraction step followed by
      exact contour detection and region-wise classification. More specifically, we
      extract possible exudate candidates using grayscale morphology and their proper
      shape is determined by a Markovian segmentation model considering edge
      information. Finally, we label the candidates as true or false ones by an
      optimally adjusted SVM classifier. For testing purposes, we considered the
      publicly available database DiaretDB1, where the proposed method outperformed
      several state-of-the-art exudate detectors. 

PMID- 25569915
TI  - Optic disc and macula detection in fundus images by means of template matching.
AB  - Various methods for detecting optic disc and macula in fundus images have been
      developed. Our aim is to propose a fairly easy method for detecting both features
      jointly. This is achieved by first correcting in homogenous luminosity using a
      polynomial approximation of the background of the images. Secondly, the use of
      the cross-correlation in the frequency domain between the images and a steerable
      template which contains both structures. The 38 photographs used in this work
      belong to a local database of patients suffering diabetic retinopathy along its
      four severity stages. Our results showed 100% optic disc centers located within
      the OD area and 90% macula centers located within the MC area. 

PMID- 25569917
TI  - Automatic retinal vessel classification using a Least Square-Support Vector
      Machine in VAMPIRE.
AB  - It is important to classify retinal blood vessels into arterioles and venules for
      computerised analysis of the vasculature and to aid discovery of disease
      biomarkers. For instance, zone B is the standardised region of a retinal image
      utilised for the measurement of the arteriole to venule width ratio (AVR), a
      parameter indicative of microvascular health and systemic disease. We introduce a
      Least Square-Support Vector Machine (LS-SVM) classifier for the first time (to
      the best of our knowledge) to label automatically arterioles and venules. We use
      only 4 image features and consider vessels inside zone B (802 vessels from 70
      fundus camera images) and in an extended zone (1,207 vessels, 70 fundus camera
      images). We achieve an accuracy of 94.88% and 93.96% in zone B and the extended
      zone, respectively, with a training set of 10 images and a testing set of 60
      images. With a smaller training set of only 5 images and the same testing set we
      achieve an accuracy of 94.16% and 93.95%, respectively. This experiment was
      repeated five times by randomly choosing 10 and 5 images for the training set.
      Mean classification accuracy are close to the above mentioned result. We conclude
      that the performance of our system is very promising and outperforms most
      recently reported systems. Our approach requires smaller training data sets
      compared to others but still results in a similar or higher classification rate. 

PMID- 25569916
TI  - Weighted ensemble based automatic detection of exudates in fundus photographs.
AB  - Diabetic retinopathy (DR) is a visual complication of diabetes, which has become
      one of the leading causes of preventable blindness in the world. Exudate
      detection is an important problem in automatic screening systems for detection of
      diabetic retinopathy using color fundus photographs. In this paper, we present a
      method for detection of exudates in color fundus photographs, which combines
      several preprocessing and candidate extraction algorithms to increase the exudate
      detection accuracy. The first stage of the method consists of an ensemble of
      several exudate candidate extraction algorithms. In the learning phase, simulated
      annealing is used to determine weights for combining the results of the ensemble
      candidate extraction algorithms. The second stage of the method uses a machine
      learning-based classification for detection of exudate regions. The experimental
      validation was performed using the DRiDB color fundus image set. The validation
      has demonstrated that the proposed method achieved higher accuracy in comparison
      to state-of-the art methods. 

PMID- 25569918
TI  - Automatic Diabetic Retinopathy detection using BossaNova representation.
AB  - The biomedical community has shown a continued interest in automated detection of
      Diabetic Retinopathy (DR), with new imaging techniques, evolving diagnostic
      criteria, and advancing computing methods. Existing state of the art for
      detecting DR-related lesions tends to emphasize different, specific approaches
      for each type of lesion. However, recent research has aimed at general frameworks
      adaptable for large classes of lesions. In this paper, we follow this latter
      trend by exploring a very flexible framework, based upon two-tiered feature
      extraction (low-level and mid-level) from images and Support Vector Machines. The
      main contribution of this work is the evaluation of BossaNova, a recent and
      powerful mid-level image characterization technique, which we contrast with
      previous art based upon classical Bag of Visual Words (BoVW). The new technique
      using BossaNova achieves a detection performance (measured by area under the
      curve - AUC) of 96.4% for hard exudates, and 93.5% for red lesions using a cross
      dataset training/testing protocol. 

PMID- 25569919
TI  - Unsupervised recognition of retinal vascular junction points.
AB  - Landmark points in retinal images can be used to create a graph representation to
      understand and to diagnose not only different pathologies of the eye, but also a
      variety of more general diseases. Aim of this paper is the description of a non
      supervised methodology to distinguish between bifurcations and crossings of the
      retinal vessels, which can be used in differentiating between arteries and veins.
      A thinned representation of the binarized image, is used to identify pixels with
      three or more neighbors. Junction points are classified into bifurcations or
      crossovers according to their geometrical and topological properties. The
      proposed approach is successfully compared with the state-of-the-art methods with
      the benchmarks DRIVE and STARE. The recall, precision and F-score average
      detection values are 91.5%, 88.8% and 89.8% respectively. 

PMID- 25569920
TI  - Estimating maximal measurable performance for automated decision systems from the
      characteristics of the reference standard. application to diabetic retinopathy
      screening.
AB  - We investigate the maximal performance that can be measured for automated binary
      decision systems in terms of area under the ROC curve (AUC), against a reference
      standard provided by human readers. The goal is to determine the required
      characteristics of the reference standard to assess and compare automated
      decision systems with a given degree of confidence, or, to determine what degree
      of confidence can be obtained given the characteristics of the reference
      standard. We modeled the expected value of the AUC that can be measured for a
      perfect decision system, given a reference standard provided either by a single
      human reader or by multiple human readers (consensus, majority vote). The
      proposed model was applied to diabetic retinopathy screening in a dataset of 874
      eye fundus examinations graded by three readers. The expected value of the AUC
      for a perfect decision system was estimated at 0.956 against a single human
      reader, and 0.990 against a 'majority wins' vote of three human readers. The Iowa
      detection program has reached the maximal performance measurable by a single
      human reader (0.929, CI: [0.897-0.962]) and is close to the maximal performance
      measurable by a 'majority wins' vote (0.955, CI: [0.939-0.972]). 

PMID- 25569921
TI  - Geometric corner extraction in retinal fundus images.
AB  - This paper presents a novel approach of finding corner features between retinal
      fundus images. Such images are relatively textureless and comprising uneven
      shades which render state-of-the-art approaches e.g., SIFT to be ineffective.
      Many of the detected features have low repeatability (<; 10%), especially when
      the viewing angle difference in the corresponding images is large. Our approach
      is based on the finding of blood vessels using a robust line fitting algorithm,
      and locating corner features based on the bends and intersections between the
      blood vessels. These corner features have proven to be superior to the state-of
      the-art feature extraction methods (i.e. SIFT, SURF, Harris, Good Features To
      Track (GFTT) and FAST) with regard to repeatability and stability in our
      experiment. Overall in average, the approach has close to 10% more repeatable
      detected features than the second best in two corresponding retinal images in the
      experiment. 

PMID- 25569922
TI  - Automatic retinal interest evaluation system (ARIES).
AB  - In recent years, there has been increasing interest in the use of automatic
      computer-based systems for the detection of eye diseases such as glaucoma, age
      related macular degeneration and diabetic retinopathy. However, in practice,
      retinal image quality is a big concern as automatic systems without consideration
      of degraded image quality will likely generate unreliable results. In this paper,
      an automatic retinal image quality assessment system (ARIES) is introduced to
      assess both image quality of the whole image and focal regions of interest. ARIES
      achieves 99.54% accuracy in distinguishing fundus images from other types of
      images through a retinal image identification step in a dataset of 35342 images.
      The system employs high level image quality measures (HIQM) to perform image
      quality assessment, and achieves areas under curve (AUCs) of 0.958 and 0.987 for
      whole image and optic disk region respectively in a testing dataset of 370
      images. ARIES acts as a form of automatic quality control which ensures good
      quality images are used for processing, and can also be used to alert operators
      of poor quality images at the time of acquisition. 

PMID- 25569923
TI  - Automated detection of choroid boundary and vessels in optical coherence
      tomography images.
AB  - Structural changes in the choroid, a layer located between the retina and sclera,
      could indicate various vision impairments. Consequently, ophthalmologists inspect
      optical coherence tomography (OCT) scans of the posterior section of the eye
      towards making diagnosis. With a view to assist diagnosis, we propose an
      automated technique for segmentation of the choroid layer. Specifically, we
      detect the upper and lower boundaries of the choroid using structural similarity
      and adaptive Hessian analysis. Subsequently, we detect choroid vessels within
      those boundaries using a level set method. Experimental results are presented
      using spectral domain (SD) OCT images. 

PMID- 25569924
TI  - Development of an electro-optically tuned optical coherence tomography system for
      imaging dental lesions.
AB  - A conventional optical coherence tomography (OCT) system was set up in-house to
      image early dental caries, identify gap formation in the bonding interface for
      restoration and secondary caries. Two-dimensional images of tooth samples was
      obtained and dental defect were identified. A novel electro-optic tuning system
      is proposed in order to improve scanning speed and to perform noiseless imaging.
      Preliminary studies were conducted with two crystals namely, LiNbO3 (Lithium
      Niobate) and KTP (Potassium Titanyl Phosphate) using a SLED source for OCT system
      and the simulated and experimental results were found to be qualitatively
      similar. The tuning range for LiNbO3 and KTP was found to be in the order of few
      micrometers whereas KTN (Potassium Tantalate Niobate) using the quadratic electro
      optic effect is expected to show scanning range of tens of micrometers. KTN based
      hybrid scanning for dental caries imaging is also planned. 

PMID- 25569925
TI  - Automatic atherosclerotic heart disease detection in intracoronary optical
      coherence tomography images.
AB  - Intracoronary optical coherence tomography (OCT) is a new invasive imaging system
      which produces high-resolution images of coronary arteries. Preliminary data
      suggests that the atherosclerotic disease can be detected from the intracoronary
      OCT images. However, manual assessment of the intracoronary OCT images is time
      consuming and subjective. In this work, we present an automatic atherosclerotic
      disease detection system on intracoronary OCT images. In the system, a
      preprocessing scheme is first applied to remove speckle noise and artifacts
      caused by catheter. Intensity, Histograms of Oriented Gradients (HOG), and Local
      Binary Patterns (LBP) are then extracted to represent the OCT image. Finally a
      linear SVM classifier is employed to detect the unhealthy subject. Four-fold
      cross-validation process is conducted to evaluate the proposed system; and a
      dataset with 200 images from healthy subjects and 200 images from unhealthy
      subjects is built to evaluate the system. The mean accuracy is 0.90 and standard
      deviation is 0.0427, which indicates that the proposed system is accurate and
      stable. 

PMID- 25569926
TI  - Automatic lumen contour detection in intravascular OCT images using Otsu
      binarization and intensity curve.
AB  - This paper proposes an automatic method for the detection of lumen contours in
      intravascular OCT images with guide wire shadow artifacts. This algorithm is
      divided into five main procedures: pre-processing, an Otsu binarization approach,
      an intensity curve approach, a lumen contour position correction, and image
      reconstruction and contour extraction. The 30 IVOCT images from six anonymous
      patients were used to verify this method and we obtained 99.2% sensitivity and
      99.7% specificity with this algorithm. 

PMID- 25569928
TI  - Speckle reduction in optical coherence tomography by matrix completion using
      bilateral random projection.
AB  - Speckle noise is problematic in optical coherence tomography (OCT) and often
      obscures the structure details. In this paper, we propose a new method to reduce
      speckle noise from multiply scanned OCT slices. The proposed method registers the
      OCT scans using a global alignment followed by a local alignment based on global
      and local motion estimation. Then low rank matrix completion using bilateral
      random projection is utilized to estimate the noise and recover the clean image.
      Experimental results show that the proposed method archives average contrast to
      noise ratio 14.90, better than 13.78 by the state-of-the-art method used in
      current OCT machines. The technology can be embedded into current OCT machines to
      enhance the image quality. 

PMID- 25569927
TI  - Optical coherence tomography imaging of cardiac trabeculae.
AB  - An integrated instrument is being developed to study live cardiac trabeculae,
      which is capable of stimulating the muscle under controlled conditions while
      measuring the heat production, force, and sarcomere length distribution. To
      improve the accuracy of estimation of stress, strain, and volumetric heat
      production, the geometry of the muscle must be known. A spectral domain optical
      coherence tomography system (SD-OCT) has been constructed and calibrated to image
      the trabecula mounted inside the instrument. This system was mounted above the
      muscle chamber and a series of equally-spaced cross-sectional images were
      obtained. These were processed using a workflow developed to extract cross
      sectional area and volume. The initial results have demonstrated the feasibility
      of using OCT to capture the overall geometry of cardiac trabecula mounted in the
      instrument. Further work will be directed to improve the image quality for larger
      samples and apply meshing algorithms to the acquired data. 

PMID- 25569929
TI  - Imaging of the 3D dynamics of flagellar beating in human sperm.
AB  - The study of the mechanical and environmental factors that regulate a fundamental
      event such as fertilization have been subject of multiple studies. Nevertheless,
      the microscopical size of the spermatozoa and the high beating frequency of their
      flagella (up to 20 Hz) impose a series of technological challenges for the study
      of the mechanical factors implicated. Traditionally, due to the inherent
      characteristics of the rapid sperm movement, and to the technological limitations
      of microscopes (optical or confocal) to follow in three dimensions (3D) their
      movement, the analysis of their dynamics has been studied in two dimensions, when
      the head is confined to a surface. Flagella propel sperm and while their head can
      be confined to a surface, flagellar movement is not restricted to 2D, always
      displaying 3D components. In this work, we present a highly novel and useful tool
      to analyze sperm flagella dynamics in 3D. The basis of the method is a 100 Hz
      oscillating objective mounted on a bright field optical microscope covering a 16
      microns depth space at a rate of ~ 5000 images per second. The best flagellum
      focused subregions were associated to their respective Z real 3D position.
      Unprecedented graphical results making evident the 3D movement of the flagella
      are shown in this work and supplemental material illustrating a 3D animation
      using the obtained experimental results is also included. 

PMID- 25569930
TI  - Comparison of normalization algorithms for cross-batch color segmentation of
      histopathological images.
AB  - Automated processing of digital histopathology slides has the potential to
      streamline patient care and provide new tools for cancer classification and
      grading. Before automatic analysis is possible, quality control procedures are
      applied to ensure that each image can be read consistently. One important quality
      control step is color normalization of the slide image, which adjusts for color
      variances (batch-effects) caused by differences in stain preparation and image
      acquisition equipment. Color batch-effects affect color-based features and reduce
      the performance of supervised color segmentation algorithms on images acquired
      separately. To identify an optimal normalization technique for histopathological
      color segmentation applications, five color normalization algorithms were
      compared in this study using 204 images from four image batches. Among the
      normalization methods, two global color normalization methods normalized colors
      from all stain simultaneously and three stain color normalization methods
      normalized colors from individual stains extracted using color deconvolution.
      Stain color normalization methods performed significantly better than global
      color normalization methods in 11 of 12 cross-batch experiments (p<;0.05).
      Specifically, the stain color normalization method using k-means clustering was
      found to be the best choice because of high stain segmentation accuracy and low
      computational complexity. 

PMID- 25569931
TI  - A non-linear iterative method for multi-layer DOT sub-surface imaging system.
AB  - Diffuse Optical Tomography (DOT) has become an emerging non-invasive technology,
      and has been widely used in clinical diagnosis. Functional near-infrared (FNIR)
      is one of the important applications of DOT. However, FNIR is used to reconstruct
      two-dimensional (2D) images for the sake of good spatial and temporal resolution.
      In this paper we propose a multiple-input and multiple-output (MIMO) based data
      extraction algorithm method in order to increase the spatial and temporal
      resolution. The non-linear iterative method is used to reconstruct better
      resolution images layer by layer. In terms of theory, the simulation results and
      original images are nearly identical. The proposed reconstruction method performs
      good spatial resolution, and has a depth resolutions capacity of three layers. 

PMID- 25569932
TI  - Three-dimensional vascular smooth muscle orientation as quantitatively assessed
      by multiphoton microscopy: mouse carotid arteries do show a helix.
AB  - Smooth muscle cells (SMCs) play a pivotal role in regulating vascular tone in
      arteries, and are therefore an essential part of constitutive models of the
      artery wall. In the present study, we developed a method to quantify in 3D the
      orientation of SMCs in the intact artery wall. We stained cell nuclei in excised
      mouse carotid arteries mounted between micropipettes and imaged these in 3D using
      two-photon laser scanning microscopy. A clustering method was used to identify
      individual nuclei. Orientations of these nuclei (as a representative of the SMC
      orientations) were found by calculating the inertia matrix eigenvectors.
      Subsequently, SMC locations and orientations were converted to cylindrical and
      spherical coordinate systems, respectively. We found SMCs to be arranged in two
      distinct layers. For each of these layers, SMC orientations were described by a
      Bingham distribution. Distributions showed a statistically significant helical
      and transversal angular component in both inner and outer layers. In conclusion,
      this study demonstrates that SMC orientation can be quantified in 3D, and shows a
      distinct helical as well as transversal orientation. The acquired distribution
      data are essential to improve current constitutive models of the artery wall, by
      describing physiological SMC orientation and dispersion. 

PMID- 25569933
TI  - A projection selection method to improve image quality in optical projection
      tomography.
AB  - Optical projection tomography (OPT) is a very important imaging tool for a
      mesoscopic-scale. It can provide three dimensional (3D) transmission and emission
      imaging. However, high-resolution OPT is limited in depth of field (DOF) due to a
      high numerical aperture, which causes a poor performance of OPT in imaging large
      samples. Moreover, it is difficult to tune the focus plane (FP) to a fixed
      position where OPT always has the best image quality in different directions. To
      address these problems, we developed a projection selection method to improve DOF
      in OPT. In each direction, our method automatically selects the best projection
      from several projections with different FP. Then, we use a series of selected
      projections for 3D reconstruction. The experimental results demonstrate that our
      method can improve the image quality comparing to a fixed FP. Moreover, our
      method is flexible to be used in other OPT setups by adding a linear stage. 

PMID- 25569935
TI  - An improved method for velocity estimation of red blood cell in microcirculation.
AB  - This paper presents a coarse-to-fine combined method for dealing with large
      displacement situations caused by low speed of frame rate in microscopic video
      sequences. Motion image estimation method utilizes the modified block matching
      method based on image warping to perform a wide range of changes in the amount of
      search comparison, and then using the optical flow method to fine adjustment
      pixel by pixel, to complete the overall precision of the estimation. In the
      evaluation experiment, we have compared both current optical flow and proposed
      method by testing them with simulated vessel images, the results of the
      estimation is quite accurate. 

PMID- 25569934
TI  - Automatic detection of microdots in the stromal layer of corneal images.
AB  - Microdots are bright, 1-2um features of the cornea. It has not been proven what
      these dots represent, but they are thought to be remnants of apoptotic cell
      death, such as lipofuscin granules. Their presence has been shown to correlate
      with corneal aging and extended contact use, both of which are linked to oxygen
      deprivation in the cornea. Confocal images of the stroma show these microdots
      mixed with larger keratocyte cells. This paper presents a method for detecting
      microdots using a two-step filtering scheme that separates the keratocyte cells
      and the microdots. Keratocyte cell locations are then used to eliminate falsely
      detected microdots. Results are compared to ground truth based on a grading scale
      from 0-5. Two graders were given a set of 50 images to grade using a GUI that
      included sample images for each of the six grades. The two graders had a
      correlation of .88 with each other. The algorithm had a correlation of .88 with
      the average of graders and .85 with each of the graders individually. 

PMID- 25569937
TI  - An efficient steganography method for hiding patient confidential information.
AB  - This paper deals with the important issue of security and confidentiality of
      patient information when exchanging or storing medical images. Steganography has
      recently been viewed as an alternative or complement to cryptography, as existing
      cryptographic systems are not perfect due to their vulnerability to certain types
      of attack. We propose in this paper a new steganography algorithm for hiding
      patient confidential information. It utilizes Pixel Value Differencing (PVD) to
      identify contrast regions in the image and a Hamming code that embeds 3 secret
      message bits into 4 bits of the cover image. In order to preserve the content of
      the region of interest (ROI), the embedding is only performed using the Region of
      Non-Interest (RONI). 

PMID- 25569936
TI  - Hyperspectroscopic imager for baby fibers.
AB  - Hyperspectral imaging system for diagnosing digestive diseases was newly
      developed in order to obtain information on pathology beyond morphology of
      lesions. In order to guide light reflected from a lesion, a baby fiber, which can
      be inserted in a forceps channel of the electronic endoscope, was also developed.
      The performance of the system was evaluated by animal experiment. Obtained
      hyperspectral data were found to have sufficient quality endurable to practical
      use. Harmful phenomena to a living body were not observed within the experiment.
      It was considered from the animal experiment that the present system could be
      practically used for humans. 

PMID- 25569938
TI  - Comparative study on shear wave speed estimation algorithms in ARFI for improving
      its reliability.
AB  - Quantitatively assessing the tissue stiffness with acoustic radiation force
      impulse (ARFI) method has proved its worth in clinical trials. Much attention has
      been focused on the research of the displacement estimation algorithm in ARFI.
      However, the subsequent shear wave speed estimation part can also affect the
      accuracy and reliability of the results. In this study, several algorithms for
      shear wave speed estimation were designed and compared using the ultrasound radio
      frequency data collected from a self-developed ARFI system. These RT based
      algorithms were classified as two types: the transformation being performed on
      the time-location displacement matrix or on the time-depth displacement matrix.
      The algorithms in Type I attempt to find the best trajectory of the shear wave
      propagation in one depth, while those in Type II try to directly find the time
      points when the wavefront passed each lateral location in the whole depth range.
      Experiments were performed on soft tissue mimicking phantom and ex vivo pork
      tissue sample. The reliability of repeated measurements and the computation time
      of these algorithms were compared to find the most stable and time-saving one for
      ARFI. The results can give us inspiration on how to design a better algorithm for
      shear wave speed estimation and help to improve the measurement reliability of
      ARFI. 

PMID- 25569939
TI  - Scanning-mode 2D acoustic radiation force impulse (s2D-ARFI) imaging based on GPU
      acceleration.
AB  - Acoustic radiation force impulse (ARFI) technique is a quantitative method for
      tissue stiffness assessment. It has been proved to be less operator dependent
      than the quasi-static elastography, and has more simple hardware architecture
      than the supersonic shearwave imaging (SSI) technique, which make it easier to be
      miniaturized for some special clinical applications. However, unlike the SSI,
      ARFI cannot provide real-time 2D images of tissue stiffness distribution mainly
      due to its data-intensive and time-consuming algorithms. In this study, the
      algorithms of ARFI were modified and improved to fit for the parallel computation
      on graphics processing unit (GPU), and the quasi-real-time scanning-mode 2D ARFI
      images (s2D-ARFI) were implemented on a self-developed compact system. High ratio
      of the time consumptions between the algorithms using CPU and using GPU has been
      verified, and it was also proved that there was no distinct difference between
      the stiffness images obtained by these two methods. The s2D-ARFI provides us an
      additional choice for quantitatively imaging the tissue stiffness, and has a
      potential to be miniaturized and used in the emergency treatments in field first
      aid and the donor evaluation for organ transplantation. 

PMID- 25569940
TI  - Cervical attenuation as a measure of preterm delivery: impact of different region
      of interest sizes.
AB  - One to five transvaginal ultrasound scans were taken of 63 women to estimate the
      microstructural changes in cervix using ultrasonic attenuation. Spectral log
      difference algorithm showed a clear decrease in attenuation as the time to
      delivery comes closer. The decrease in attenuation occurs earlier in preterm
      birth compared to full term birth which can be used as a predictor for preterm
      birth. Attenuation estimate did not improve as the ROI size increased. 

PMID- 25569941
TI  - Anisotropic diffusion filter based edge enhancement for the segmentation of
      carotid intima-media layer in ultrasound images using variational level set
      method without re-initialisation.
AB  - In this work an attempt has been made to enhance the edges and segment the
      boundary of intima-media layer of Common Carotid Artery (CCA) using anisotropic
      diffusion filter and level set method. Ultrasound B mode longitudinal images of
      normal and abnormal images of common carotid arteries are used in this study. The
      images are subjected to anisotropic diffusion filter to generate edge map. This
      edge map is used as a stopping boundary in variational level set method without
      re-initialisation to segment the intima-media layer. Geometric features are
      extracted from this layer and analyzed statistically. Results show that
      anisotropic diffusion filtering is able to extract the edges in both normal and
      abnormal images. The obtained edge maps are found to have high contrast and sharp
      edges. The edge based variational level set method is able to segment the intima
      media layer precisely from common carotid artery. The extracted geometrical
      features such as major axis and extent are found to be statistically significant
      in differentiating normal and abnormal images. Thus this study seems to be
      clinically useful in diagnosis of cardiovascular disease. 

PMID- 25569942
TI  - A setup for the assessment of the effect of tubular confinement on the acoustic
      response of microbubbles.
AB  - Ultrasound contrast agents are gas filled microbubbles which produced enhanced
      echoes in ultrasound imaging thus allowing the acquisition of detailed
      information on the path of blood. It is theoretically known that the size of a
      vessel affects the behavior of a microbubble, which could potentially be used to
      discriminate different sized vessels. This information would be useful in the
      monitoring of neovascularization in tumor growth or treatment. However, currently
      it is not possible to identify the vessel diameter by any means of signal
      processing of microbubble echoes. In order to assess microbubble behavior when
      confined in tubes we compared the acoustic backscatter from biSphereTM
      microbubbles both free in water and flowing in 200 MUm diameter tubes that are
      similar in size to arterioles. Experimental systems that allow the interrogation
      of individual microbubbles were designed and modified to allow investigation of
      both free microbubbles and those in tubes. Unprocessed single microbubble RF data
      were collected, allowing the calculation of both the fundamental and second
      harmonic components of the backscattered signal. Microbubbles confined in tubes
      had lower amplitude response compared to unconfined microbubbles. On consecutive
      insonations of the same microbubble, free microbubbles produced echoes above
      noise more often than confined microbubbles. This setup may be used to
      investigate microbubble behavior in a range of smaller tubes with diameters
      similar to capillaries thus enabling signal processing design for vessel
      differentiation. 

PMID- 25569943
TI  - Relation of arterial stiffness and axial motion of the carotid artery wall - a
      pilot study to test our motion tracking algorithm in practice.
AB  - Recently researchers have shown growing interest in axial motion of common
      carotid artery wall. The amplitude of the axial motion of the wall has been
      initially linked to arterial stiffness and the direction of the axial stretch has
      been noted to vary, although not highlighted in the studies. In this study, an
      enhanced block matching algorithm, developed in our earlier study, was used to
      measure 2D-motion of the human carotid artery wall. A total of 19 healthy
      subjects were imaged and divided into two groups based on whether their axial
      motion of intima-media in left common carotid artery was primarily oriented along
      or against the direction of the blood flow. Statistically significant differences
      in two independent indices of arterial stiffness, as well as in the size of the
      artery, were found between the groups, suggesting that retrograde motion of
      intima-media is associated with smaller carotid arteries and is a possible sign
      of arterial stiffness. 

PMID- 25569944
TI  - Ultrasound imaging and semi-automatic analysis of active muscle features in
      electrical stimulation by optical flow.
AB  - Ultrasound imaging is an effective way to measure the muscle activity in
      electrical stimulation studies. However, it is a time consuming task to manually
      measure pennation angle and muscle thickness, which are the benchmark features to
      analyze muscle activity from the ultrasound imaging. In previous studies, the
      muscle features were measured by calculating optical flow of the pennation angle
      by using only fibers of a muscle from the ultrasound, without carefully
      considering moving muscle edges during active and passive contraction. Therefore,
      this study aimed to measure the pennation angle and muscle thickness by using the
      edges and fibers of a muscle in a quantitative way in a semi-automatic optical
      flow based approach. The results of the semi-automatic analysis were compared to
      that of manual measurement. Through the comparison, it is clear that the proposed
      algorithm could achieve higher accuracy in tracking the thickness and pennation
      angle for a sequence of ultrasound images. 

PMID- 25569945
TI  - A multi-feature classification approach to detect sleep apnea in an ultrasonic
      upper airway occlusion detector system.
AB  - Obstructive Sleep Apnea (OSA) is the most common form of sleep disorder
      breathing. It is estimated that this insidious disease affects 15% of the US
      adult population. Current procedure of diagnosing OSA requires polysomnography
      (NPSG) conducted in accredited sleep laboratories and the data getting scored by
      certified sleep technicians, a costly process that is not readily available in
      all areas. Ultrasonic techniques are increasingly used in the area of medical
      diagnosis and treatments due to their safety and economic costs. This paper
      investigates a feasibility study of a multi-channel ultrasonic OSA detection
      system. The approach utilizes wavelet-based as well as temporal and spectral
      features extracted from multiple ultrasound waves transmitted through patient's
      neck during sleep. Using NPSG data as gold standard, the proposed classifier
      makes a preliminary decision on the data sequence by labeling epochs as normal or
      apneic. A Finite State Machine (FSM) is employed to update the classified labels
      for a more robust detection. Experimental results on three sleep disordered
      patients suggest that it may be feasible to consider the proposed approach for an
      ultrasound based detection system. 

PMID- 25569946
TI  - Novel method for detection of Sleep Apnoea using respiration signals.
AB  - Polysomnography (PSG) studies are considered the "gold standard" for the
      diagnosis of Sleep Apnoea (SA). Identifying cessations of breathing from long
      lasting PSG recordings manually is a labour-intensive and time-consuming task for
      sleep specialist, associated with inter-scorer variability. In this study a
      simplified, semi-automatic, three-channel method for detection of SA patients is
      proposed in order to increase analysis reliability and diagnostic accuracy in the
      clinic. The method is based on characteristic features, such as respiration
      stoppages pr. hour and the total number of oxygen desaturations > 3%, extracted
      from the thorax and abdomen respiration effort belts, and the oxyhemoglobin
      saturation (SaO2), fed to an Elastic Net classifier and validated according to
      American Academy of Sleep Medicine (AASM) using the patients' AHI value. The
      method was applied to 109 patient recordings and resulted in a very high SA
      classification with accuracy of 97.9%. The proposed method reduce the time spent
      on manual analysis of respiration stoppages and the inter- and intra-scorer
      variability, and may serve as an alternative screening method for SA. 

PMID- 25569947
TI  - Automated analysis of respiratory behavior for the prediction of apnea in infants
      following general anesthesia.
AB  - Infants recovering from general anesthesia are at risk of postoperative apnea
      (POA), a potentially life threatening event. There is no accurate way to identify
      which infants will experience POA, and thus all infants with postmenstrual age <;
      60 weeks are monitored for apnea in hospital postoperatively. Using a
      comprehensive, automated analysis of the postoperative breathing patterns, we
      identified the occurrence of respiratory pauses in 24 infants at age risk for
      POA. We determined the POA category for each infant by using K-medoids to cluster
      the duration of the longest respiratory pause. Two clusters were identified,
      corresponding to APNEA and NO-APNEA, with a threshold of 14.6 s, a value
      consistent with the clinically accepted threshold of 15 s. K-medoids derived POA
      labels were used to evaluate the predictive ability of demographic and anesthetic
      management variables. Weight and the intraoperative doses of atropine, propofol,
      and opioids discriminated between the APNEA and NO-APNEA groups. A linear
      Gaussian discriminant analysis classifier provided a very good classification
      with a probability of detection PD = 0.73 and a probability of false alarm PFA =
      0.22. This approach provides a promising tool for the systematic, objective study
      of infants at risk of POA. 

PMID- 25569948
TI  - Modelling fluid accumulation in the neck using simple baseline fluid metrics:
      implications for sleep apnea.
AB  - Obstructive sleep apnea (OSA) is a common respiratory disorder among adults.
      Recently we have shown that sedentary lifestyle causes an increase in diurnal leg
      fluid volume (LFV), which can shift into the neck at night when lying down to
      sleep and increase OSA severity. The purpose of this work was to investigate
      various metrics that represent baseline fluid retention in the legs and examine
      their correlation with neck fluid volume (NFV) and to develop a robust model for
      predicting fluid accumulation in the neck. In 13 healthy awake non-obese men, LFV
      and NFV were recorded continuously and simultaneously while standing for 5
      minutes and then lying supine for 90 minutes. Simple regression was used to
      examine correlations between baseline LFV, baseline neck circumference (NC) and
      change in LFV with the outcome variables: change in NC (DeltaNC) and in NFV
      (DeltaNFV90) after lying supine for 90 minutes. An exhaustive grid search was
      implemented to find combinations of input variables which best modeled outcomes.
      We found strong positive correlations between baseline LFV (supine and standing)
      and DeltaNFV90. Models developed for predicting DeltaNFV90 included baseline
      standing LFV, baseline NC combined with change in LFV after lying supine for 90
      minutes. These correlations and the developed models suggest that a greater
      baseline LFV might contribute to increased fluid accumulation in the neck. These
      results give more evidence that sedentary lifestyle might play a role in the
      pathogenesis of OSA by increasing the baseline LFV. The best models for
      predicting DeltaNC include baseline LFV and NC; they improved accuracies of
      estimating DeltaNC over individual predictors, suggesting that a combination of
      baseline fluid metrics is a good predictor of the change in NC while lying
      supine. Future work is aimed at adding additional baseline demographic features
      to improve model accuracy and eventually use it as a screening tool to predict
      severity of OSA prior to sleep. 

PMID- 25569950
TI  - Characterization of movements during restless sleep in children: a pilot study.
AB  - Actigraphy is effective at monitoring circadian rhythms, but often misidentifies
      periods of restless sleep (defined here as sleep periods with movement) as wake,
      and periods of quiet wake as sleep. This limitation restricts the effectiveness
      of actigraphy for investigating sleep disorders. Our objective in this study was
      to investigate a time-frequency representation of movement during sleep and wake
      which could ultimately aid in improving classification performance by reducing
      false wake detections. As a pilot study, we investigate the characteristics of
      manually labelled movements from six patients (aged 6-12 years, 3 male) during
      sleep and wake using the over complete discrete wavelet decomposition. The
      difference between the median wavelet coefficients were analyzed for 30 movement
      segments from six movement categories during sleep and wake. We found that, in
      general, the temporal location of high energy coefficients and the energy of the
      high frequency bands differed between movements during sleep and wake. This
      indicates that we are able to differentiate movement during sleep and wake with a
      time-frequency representation. This representation may improve the sleep and wake
      classification performance by identifying movements specific to sleep and wake.
      This will likely improve the poor specificity inherent in conventional
      actigraphy. 

PMID- 25569949
TI  - Effect of apnea duration on apnea induced variations in cerebral blood flow
      velocity and arterial blood pressure.
AB  - Obstructive Sleep Apnea (OSA), defined by shallow breaths or complete cessation
      of breathing for more than 10s, is a significant contributing factor for the
      developments of hypertension, myocardial infarction, stroke and
      neuropsychological impairments. In this study, we have investigated the relation
      between apnea duration and apnea induced variations in cerebral blood flow
      velocity (CBFV) concomitant with blood pressure changes in 9 sleep apnea subjects
      (8 male and 1 female; Age: 46.0+/-11.6 years; BMI: 34.5+/-7.8 kg/m(2); AHI:
      81.6+/-41). As apnea duration increased from 10s to greater than 30s, the mean
      percentage rise in CBFV increased from 22% to 42% for amplitude and 22% to 33%
      for area respectively. For blood pressure, the values increased from 14% to 26%
      for amplitude and 14% to 23% for area respectively. The results suggest that the
      apnea duration has a measurable effect on the degree of rise in both cerebral
      blood flow velocity and arterial blood pressure during apnea episodes (p=0.0002).

PMID- 25569951
TI  - An autoregulation unit for enabling adaptive control of sensorized left
      ventricular assist device.
AB  - This paper describes an integrated system for facing heart failures (HF) in an
      innovative way. Existing left ventricular assist devices (LVAD or VAD) are
      usually devoted to blood pumping without the possibility to adapt the speed to
      patient conditions during everyday activities. This is essentially due to the
      lack of sensorization, bulkiness, and the need of relying on device-specific
      controllers with reduced computing ability for the existing ventricular assist
      systems. In this work, an innovative integrated and portable device, the ARU, is
      presented for enhancing VADs applicability as a long-term solution to HF. The ARU
      is an universal device able to fulfill with the needs of sensorized VADs in terms
      of data storing, continuous monitoring, autoregulation and adaptation to patient
      condition changes during daily activities. The ARU is able to wirelessly
      interface wearable devices for offering additional monitoring features from
      remote. The ARU functionalities on bench have been tested by the interfacing with
      a sensorized VAD platform in order to prove the feasibility of the approach.
      Experiments of local and remote VAD speed changes and autoregulation algorithms
      have been successfully tested showing response time of 1 s. 

PMID- 25569953
TI  - Safety considerations for wireless delivery of continuous power to implanted
      medical devices.
AB  - Wireless power systems for use with implants are referred to as transcutaneous
      energy transmission systems (TETS) and consist of an implanted secondary coil and
      an external primary coil along with supporting electronics. A TETS system could
      be used to power ventricular assist systems and eliminate driveline infections.
      There are both direct and indirect safety concerns that must be addressed when
      continuously transferring power through the skin. Direct safety concerns include
      thermal tissue damage caused by exposure to the electromagnetic fields, coil
      heating effects, and potential unwanted nerve stimulation. Indirect concerns are
      those caused by potential interference of the TETS system with other implanted
      devices. Wireless power systems are trending towards higher frequency operation.
      Understanding the limits for safe operation of a TETS system across a range of
      frequencies is important. A low frequency and a high frequency implementation are
      simulated to demonstrate the impact of this trend for a VAD application. 

PMID- 25569952
TI  - Experimental integration of Autoregulation Unit for left ventricular assist
      devices in a cardiovascular hybrid simulator.
AB  - In this paper, an Autoregulation Unit (ARU) for left ventricular sensorized
      assist devices (LVAD) has been used with a cardiovascular hybrid simulator
      mimicking physiological and pathological patient conditions. The functionalities
      of the ARU have been demonstrating for the successful receiving and visualization
      of system parameters, sending of commands for LVAD speed changes, and enabling of
      the autonomous flow control algorithm. Experiments of speed changes and
      autoregulation are reported, showing the feasibility of the approach for both
      local and remote control of a LVAD. 

PMID- 25569954
TI  - Application of a search algorithm using stochastic behaviors to autonomous
      control of a ventricular assist device.
AB  - A ventricular assist device (VAD) is a device with mechanical pumps implanted
      adjacent to the patient's native heart to support the blood flow. Mechanical
      circulatory support using VADs has been an essential therapeutic tool for
      patients with severe heart failure waiting for a heart transplant in clinical
      site. Adaptive control of VADs that automatically adjust the pump output with
      changes in a patient state is one of the important approaches for enhanced
      therapeutic efficacy, prevention of complications and quality of life
      improvement. However adaptively controlling a VAD in the realistic situation
      would be difficult because it is necessary to model the whole including the VAD
      and the cardiovascular dynamics. To solve this problem, we propose an application
      of attractor selection algorithm using stochastic behavior to a VAD control
      system. In this study, we sought to investigate whether this proposed method can
      be used to adaptively control of a VAD in the simple case of a continuous flow
      VAD. The flow rate control algorithm was constructed on the basis of a
      stochastically searching algorithm as one example of application. The validity of
      the constructed control algorithm was examined in a mock circuit. As a result, in
      response to a low-flow state with the different causes, the flow rate of the pump
      reached a target value with self adaptive behavior without designing the detailed
      control rule based on the experience or the model of the control target. 

PMID- 25569955
TI  - In-vitro evaluation of physiological controller response of rotary blood pumps to
      changes in patient state.
AB  - Rotary blood pumps (RBPs) have a low sensitivity to preload changes when run at
      constant speed, which can lead to harmful ventricular suction events. Therefore a
      control mechanism is needed to adjust RBP speed in response to patient demand,
      but an appropriate response time for physiological control strategies to these
      changes in patient demand has not been determined. This paper aims to evaluate
      the response of a simulated healthy heart with those of different RBP control
      techniques during exercise simulations and a Valsalva manoeuver. A mock
      circulation loop was used to simulate the response of a healthy heart to these
      changes in patient state. The generated data was compared with a simulated RBP
      (VentrAssist) supported left heart failure condition. A range of control
      techniques including constant speed, proportional integral (PI) (active control)
      and a compliant inflow cannula (passive control) were used to achieve restored
      haemodynamics and evaluate controller response time. Controllers that responded
      faster (active control) or slower (active control and constant speed mode) than
      the native heart's response led to ventricular suction. Active control systems
      can respond both faster or slower than the heart depending on the controller
      gains. A control system that responded similar to the native heart was able to
      prevent ventricular suction. This study concluded that a physiological control
      system should mimic the response of the native heart to changes in patient state
      in order to prevent ventricular suction. 

PMID- 25569956
TI  - Specifying informative experiment stimulation conditions for resolving dynamical
      uncertainty in biological systems.
AB  - A computationally efficient model-based design of experiments (MBDOE) strategy is
      developed to plan an optimal experiment by specifying the experimental
      stimulation magnitudes and measurement points. The strategy is extended from
      previous work which optimized the experimental design over a space of measurable
      species and time points. We include system inputs (stimulation conditions) in the
      experiment design search to investigate if the addition of perturbations enhances
      the ability of the MBDOE method to resolve uncertainties in system dynamics. The
      MBDOE problem is made computationally tractable by using a sparse-grid
      approximation of the model output dynamics, pre-specifying the time points at
      which the input or experimental perturbations can be applied, and creating
      scenario trees to explore the endogenous uncertainty. Consecutive scenario trees
      are used to determine the best input magnitudes and select the optimal associated
      measurement species and time points. We demonstrate the effectiveness of this
      strategy on a T-Cell Receptor (TCR) signaling pathway model. 

PMID- 25569957
TI  - A novel extreme learning machine for hypoglycemia detection.
AB  - Hypoglycemia is a common side-effect of insulin therapy for patients with type 1
      diabetes mellitus (T1DM) and is the major limiting factor to maintain tight
      glycemic control. The deficiency in glucose counter-regulation may even lead to
      severe hypoglycaemia. It is always threatening to the well-being of patients with
      T1DM since more severe hypoglycemia leads to seizures or loss of consciousness
      and the possible development of permanent brain dysfunction under certain
      circumstances. Thus, an accurate early detection on hypoglycemia is an important
      research topic. With the use of new emerging technology, an extreme learning
      machine (ELM) based hypoglycemia detection system is developed to recognize the
      presence of hypoglycemic episodes. From a clinical study of 16 children with
      T1DM, natural occurrence of nocturnal hypoglycemic episodes are associated with
      increased heart rates (p <; 0.06) and increased corrected QT intervals (p <;
      0.001). The overall data were organized into a training set with 8 patients (320
      data points) and a testing set with 8 patients (269 data points). By using the
      ELM trained feed-forward neural network (ELM-FFNN), the testing sensitivity (true
      positive) and specificity (true negative) for detection of hypoglycemia is 78 and
      60% respectability. 

PMID- 25569958
TI  - A method for modeling oxygen diffusion in an agent-based model with application
      to host-pathogen infection.
AB  - This paper describes a method for incorporating a diffusion field modeling oxygen
      usage and dispersion in a multi-scale model of Mycobacterium tuberculosis (Mtb)
      infection mediated granuloma formation. We implemented this method over a
      floating-point field to model oxygen dynamics in host tissue during chronic phase
      response and Mtb persistence. The method avoids the requirement of satisfying the
      Courant-Friedrichs-Lewy (CFL) condition, which is necessary in implementing the
      explicit version of the finite-difference method, but imposes an impractical
      bound on the time step. Instead, diffusion is modeled by a matrix-based, steady
      state approximate solution to the diffusion equation. Presented in figure 1 is
      the evolution of the diffusion profiles of a containment granuloma over time. 

PMID- 25569959
TI  - A full-wave phase aberration correction method for transcranial high-intensity
      focused ultrasound brain therapies.
AB  - Transcranial high-intensity focused ultrasound has recently been used to
      noninvasively treat several types of brain disorders. However, due to the large
      differences in acoustic properties of skulls and the surrounding soft tissue, it
      can be a challenge to adequately focus an ultrasonic beam through the skull. We
      present a novel, fast, full-wave method of correcting the aberrations caused by
      the skull by phasing the elements of a phased-array transducer to create
      constructive interference at the target. Because the method is full-wave, it also
      allows for trajectory planning by determining the phases required for multiple
      target points with negligible additional computational costs. Experimental
      hydrophone scans with an ex vivo skull sample using a 256-element 1-MHz
      transducer show an improvement of 6.2% in peak pressure at the focus and a
      reduction of side-lobe pressure by a factor of 2.31. Additionally, mispositioning
      of the peak pressure from the intended treatment location is reduced from 2.3 to
      0.5 mm. 

PMID- 25569960
TI  - Using metabolomic and transportomic modeling and machine learning to identify
      putative novel therapeutic targets for antibiotic resistant Pseudomonad
      infections.
AB  - Hospital acquired infections sicken or kill tens of thousands of patients every
      year. These infections are difficult to treat due to a growing prevalence of
      resistance to many antibiotics. Among these hospital acquired infections,
      bacteria of the genus Pseudomonas are among the most common opportunistic
      pathogens. Computational methods for predicting potential novel antimicrobial
      therapies for hospital acquired Pseudomonad infections, as well as other hospital
      acquired infectious pathogens, are desperately needed. Using data generated from
      sequenced Pseudomonad genomes and metabolomic and transportomic computational
      approaches developed in our laboratory, we present a support vector machine
      learning method for identifying the most predictive molecular mechanisms that
      distinguish pathogenic from non-pathogenic Pseudomonads. Predictions were highly
      accurate, yielding F-scores between 0.84 and 0.98 in leave one out cross
      validations. These mechanisms are high-value targets for the development of new
      antimicrobial therapies. 

PMID- 25569961
TI  - Supervised method for construction of microRNA-mRNA networks: application in
      cardiac tissue aging dataset.
AB  - MicroRNAs play an important role in regulation of gene expression, but still
      detection of their targets remains a challenge. In this work we present a
      supervised regulatory network inference method with aim to identify potential
      target genes (mRNAs) of microRNAs. Briefly, the proposed method exploiting mRNA
      and microRNA expression trains Random Forests on known interactions and
      subsequently it is able to predict novel ones. In parallel, we incorporate
      different available data sources, such as Gene Ontology and ProteinProtein
      Interactions, to deliver biologically consistent results. Application in both
      benchmark data and an experiment studying aging showed robust performance. 

PMID- 25569962
TI  - Biologically-motivated system identification: application to microbial growth
      modeling.
AB  - This paper presents a new method for identification of system models that are
      linear in parametric structure, but arbitrarily nonlinear in signal operations.
      The strategy blends traditional system identification methods with three modeling
      strategies that are not commonly employed in signal processing: linear-time
      invariant-in-parameters models, set-based parameter identification, and
      evolutionary selection of the model structure. This paper reports recent advances
      in the theoretical foundation of the methods, then focuses on the operation and
      performance of the approach, particularly the evolutionary model determination.
      The method is applied to the modeling of microbial growth by Monod Kinetics. 

PMID- 25569963
TI  - A fast sequence assembly method based on compressed data structures.
AB  - Assembling a large genome using next generation sequencing reads requires large
      computer memory and a long execution time. To reduce these requirements, a memory
      and time efficient assembler is presented from applying FM-index in JR-Assembler,
      called FMJ-Assembler, where FM stand for FMR-index derived from the FM-index and
      BWT and J for jumping extension. The FMJ-Assembler uses expanded FM-index and BWT
      to compress data of reads to save memory and jumping extension method make it
      faster in CPU time. An extensive comparison of the FMJ-Assembler with current
      assemblers shows that the FMJ-Assembler achieves a better or comparable overall
      assembly quality and requires lower memory use and less CPU time. All these
      advantages of the FMJ-Assembler indicate that the FMJ-Assembler will be an
      efficient assembly method in next generation sequencing technology. 

PMID- 25569965
TI  - Modeling collective & intelligent decision making of multi-cellular populations.
AB  - In the presence of unpredictable disturbances and uncertainties, cells
      intelligently achieve their goals by sharing information via cell-cell
      communication and making collective decisions, which are more reliable compared
      to individual decisions. Inspired by adaptive sensor network algorithms studied
      in communication engineering, we propose that a multi-cellular adaptive network
      can convert unreliable decisions by individual cells into a more reliable cell
      population decision. It is demonstrated using the effector T helper (a type of
      immune cell) population, which plays a critical role in initiating immune
      reactions in response to invading foreign agents (e.g., viruses, bacteria, etc.).
      While each individual cell follows a simple adaptation rule, it is the combined
      coordination among multiple cells that leads to the manifestation of "self
      organizing" decision making via cell-cell communication. 

PMID- 25569964
TI  - Analysis of the HIV eradication phenomenon at the early stage of infection with
      an extracellular deterministic model.
AB  - We investigate the phenomenon of HIV eradication at the early stage of the
      infection and evaluate the chance of the eradication with a mathematical model.
      We employ an extracellular deterministic model of the HIV infection dynamics and
      modify the model to include the pharmacokinetics and pharmacodynamics of
      antiretroviral HIV drugs. In addition we consider clinical experiments for the
      prevention of HIV infection using pre-exposure chemoprophylaxis treatment.
      Exploiting the mathematical model we implement the experiment numerically. The
      study in this paper is supported by the clinical results and provides a
      theoretical explanation for the results. The result suggests that the protocol of
      the experiment eradicates the virus in HIV infected patients. 

PMID- 25569966
TI  - Latent force models for describing transcriptional regulation processes in the
      embryo development problem for the Drosophila melanogaster.
AB  - In the embryo development problem for the Drosophila melanogaster, a set of
      molecules known as mor-phogens are responsible for the embryo segmentation. These
      morphogens are encoded by different genes, including the GAP genes, maternal
      coordination genes and pair-rule genes. One of the maternal coordination genes
      encodes the Bicoid morphogen, which is the responsible for the development of the
      Drosophila embryo at the anterior part and for the control and regulation of the
      GAP genes in segmentation of the early development of the Drosophila
      melanogaster. The work presented in this document, reports a methodology that
      tends to integrate mechanistic and data driven based models, aiming at making
      inference over the mRNA Bicoid from gene expression data at the protein level for
      the Bicoid morphogen. The fundamental contribution of this work is the
      description of the concentration gradient of the Bicoid morphogen in the
      continuous spatio-temporal domain as well as the output regression (gene
      expression at protein level) using a Gaussian process described by a
      mechanistically inspired covariance function. Regression results and metrics
      computed for the Bicoid protein expression both in the temporal and spatial
      domains, showed outstanding performance with respect to reported experiments from
      previous studies. In this paper, a correlation coefficient of r = 0.9758 against
      a correlation coefficient of r = 0.9086 is being reported, as well as a SMSE of
      0.0303+/-0.1512 against a SMSE of 0.1106+/-0.5090 and finally reporting a MSLL of
      -1.7036 +/- 1.3472 against -1.0151+/-1.7669. 

PMID- 25569967
TI  - Polynomial Chaos decomposition applied to stochastic dosimetry: study of the
      influence of the magnetic field orientation on the pregnant woman exposure at 50
      Hz.
AB  - Polynomial Chaos (PC) is a decomposition method used to build a meta-model, which
      approximates the unknown response of a model. In this paper the PC method is
      applied to the stochastic dosimetry to assess the variability of human exposure
      due to the change of the orientation of the B-field vector respect to the human
      body. In detail, the analysis of the pregnant woman exposure at 7 months of
      gestational age is carried out, to build-up a statistical meta-model of the
      induced electric field for each fetal tissue and in the fetal whole-body by means
      of the PC expansion as a function of the B-field orientation, considering a
      uniform exposure at 50 Hz. 

PMID- 25569968
TI  - Hands-free interface for surgical procedures based on foot movement patterns.
AB  - A hands-free interface has been developed to allow a single surgeon to control a
      locally operated forceps manipulating robot. It is based on the use of a pressure
      sensor sheet placed on the floor to measure temporal changes in the center of
      gravity of the operator's foot, in addition to the applied force. Pattern
      recognition was carried out during trials with endoscope specialists and students
      for six different types of foot movements. The specialist patterns were then used
      to develop an interface for controlling a robot with five degrees of freedom.
      Using this control interface, it was found that the robot could successfully
      handle a model organ during simulated surgery. 

PMID- 25569970
TI  - Effect of the thickness and nonlinear elasticity of tissue on the success of
      surgical stapling for laparoscopic liver resection.
AB  - Recently, the range of applications of surgical staplers has been extended to
      include laparoscopic liver resection because manipulation of a surgical stapler
      is very simple. Revealing the causes of stapling failure and suggesting a method
      to solve stapling failure are important for safe laparoscopic liver resection.
      Surgeons say that tissues make stapling more likely to fail if they are thick and
      brittle. However, the combinatorial effect of the thickness and stiffness of
      tissues on the success of surgical stapling for laparoscopic liver resection has
      not been investigated. Therefore, the objective of the present study was to
      investigate the effect of tissue thickness and tissue stiffness on the success
      rate (SR) of surgical stapling. From ex vivo stapling experimental results using
      pig livers, it is suggested that the effect of tissue thickness is greater than
      the effect of tissue stiffness on the SR of stapling. If tissue thickness is 5
      mm, the SR of stapling is high regardless of the magnitude of the tissue
      stiffness parameter. However, if tissue thickness is >10 mm, the SR of stapling
      has a relationship with nonlinear viscoelastic parameters. Therefore, the SR of
      stapling could be predicted from tissue thickness and nonlinear elastic
      parameters. 

PMID- 25569969
TI  - A 3D virtual reality simulator for training of minimally invasive surgery.
AB  - For the last decade, remarkable progress has been made in the field of
      cardiovascular disease treatment. However, these complex medical procedures
      require a combination of rich experience and technical skills. In this paper, a
      3D virtual reality simulator for core skills training in minimally invasive
      surgery is presented. The system can generate realistic 3D vascular models
      segmented from patient datasets, including a beating heart, and provide a real
      time computation of force and force feedback module for surgical simulation.
      Instruments, such as a catheter or guide wire, are represented by a multi-body
      mass-spring model. In addition, a realistic user interface with multiple windows
      and real-time 3D views are developed. Moreover, the simulator is also provided
      with a human-machine interaction module that gives doctors the sense of touch
      during the surgery training, enables them to control the motion of a virtual
      catheter/guide wire inside a complex vascular model. Experimental results show
      that the simulator is suitable for minimally invasive surgery training. 

PMID- 25569971
TI  - Development of a coordinated controller for robot-assisted shape memory alloy
      actuated needle for prostate brachytherapy.
AB  - This paper deals with the development of a coordinated control system for a robot
      and robot-driven shape memory alloy (SMA) actuated needle to follow a curvilinear
      path for percutaneous intervention. The robot driving the needle is considered as
      the outer loop and the non-linear SMA actuated flexible needle system forms the
      inner loop. The two feedback control loops are coordinated in such a way that the
      robot drives the needle considering the needle's actual deflection so that the
      needle tip reaches the target location with an acceptable accuracy. Simulation
      results are presented to verify the efficacy of the controller for tracking the
      overall desired trajectory which includes the combined trajectory of the robot
      and the needle. 

PMID- 25569972
TI  - Scaled position-force tracking for wireless teleoperation of miniaturized
      surgical robotic system.
AB  - Miniaturized surgical robotic system presents promising trend for reducing
      invasiveness during operation. However, cables used for power and communication
      may affect its performance. In this paper we chose Zigbee wireless communication
      as a means to replace communication cables for miniaturized surgical robot.
      Nevertheless, time delay caused by wireless communication presents a new
      challenge to performance and stability of the teleoperation system. We proposed a
      bilateral wireless teleoperation architecture taking into consideration of the
      effect of position-force scaling between operator and slave. Optimal position
      force tracking performance is obtained and the overall system is shown to be
      passive with a simple condition on the scaling factors satisfied. Simulation
      studies verify the efficiency of the proposed scaled wireless teleoperation
      scheme. 

PMID- 25569973
TI  - Modeling and control of tissue compression and temperature for automation in
      robot-assisted surgery.
AB  - Robotic surgery is being used widely due to its various benefits that includes
      reduced patient trauma and increased dexterity and ergonomics for the operating
      surgeon. Making the whole or part of the surgical procedure autonomous increases
      patient safety and will enable the robotic surgery platform to be used in
      telesurgery. In this work, an Electrosurgery procedure that involves tissue
      compression and application of heat such as the coaptic vessel closure has been
      automated. A MIMO nonlinear model characterizing the tissue stiffness and
      conductance under compression was feedback linearized and tuned PID controllers
      were used to control the system to achieve both the displacement and temperature
      constraints. A reference input for both the constraints were chosen as a ramp and
      hold trajectory which reflect the real constraints that exist in an actual
      surgical procedure. Our simulations showed that the controllers successfully
      tracked the reference trajectories with minimal deviation and in finite time
      horizon. The MIMO system with controllers developed in this work can be used to
      drive a surgical robot autonomously and perform electrosurgical procedures such
      as coaptic vessel closures. 

PMID- 25569974
TI  - Design and development of miniature parallel robot for eye surgery.
AB  - A five degree-of-freedom (DOF) miniature parallel robot has been developed to
      precisely and safely remove the thin internal limiting membrane in the eye ground
      during vitreoretinal surgery. A simulator has been developed to determine the
      design parameters of this robot. The developed robot's size is 85 mm * 100 mm *
      240 mm, and its weight is 770 g. This robot incorporates an emergency instrument
      retraction function to quickly remove the instrument from the eye in case of
      sudden intraoperative complications such as bleeding. Experiments were conducted
      to evaluate the robot's performance in the master-slave configuration, and the
      results demonstrated that it had a tracing accuracy of 40.0 MUm. 

PMID- 25569975
TI  - System characterization of a novel haptic interface for natural orifice
      translumenal endoscopic surgery simulation.
AB  - Natural orifice translumenal endoscopic surgery (NOTES) is a minimally invasive
      procedure, which utilizes the body's natural orifices to gain access to the
      peritoneal cavity. The VTEST((c)) is a virtual reality NOTES simulator developed
      at the CeMSIM at RPI to train surgeons in NOTES. A novel 2 DOF decoupled haptic
      device was designed and built for this simulator. The haptic device can render
      5.62 N and 190.05 N-mm of continuous force and torque respectively. In this work
      we have evaluated the haptic interface and developed a model to accurately
      describe the system behavior, to further incorporate into an impedance type
      controller for realistic haptic rendering in the VTEST((c)). 

PMID- 25569976
TI  - Path planning for robot-assisted active flexible needle using improved Rapidly
      Exploring Random trees.
AB  - In robot-assisted needle-based medical procedures, path planning for a flexible
      needle is challenging with regard to time consumption and searching robustness
      for the solution due to the nonholonomic motion of the needle tip and the
      presence of anatomic obstacles and sensitive organs in the intended needle path.
      We propose a novel and fast path planning algorithm for a robot-assisted active
      flexible needle. The algorithm is based on Rapidly-Exploring Random Trees
      combined with reachability-guided strategy and greedy heuristic strategy. Linear
      segments are taken into consideration to the paths, and insertion orientations
      are relaxed by the introduction of the linear segments. The proposed algorithm
      yields superior results as compared to the commonly used algorithm in terms of
      computational speed, form of path and robustness of searching ability, which
      potentially can make it suitable for the real-time intraoperative planning for
      clinical procedures. 

PMID- 25569977
TI  - Development of a small sucker manipulator for underwater surgery support.
AB  - WaFLES (Water-Filled LaparoEndoscopic Surgery) is an operative method suggested
      by Igarashi et al., which has several advantages, such as, preventing the drying
      of inner organs, and being able to use ultrasound devices for real time
      monitoring. However, grasping of inner organs with usual forceps for move and
      incision purpose is difficult. Therefore our ultimate goal is to develop a small
      sucker manipulator for WaFLES support. Experiments were conducted to explore
      suitable suction cups for underwater application, and suitable structure (cup-to
      cup distance, elasticity of binding material, layouts of multiple cups) for a
      multiple-cup assembly, in terms of adsorption force and tolerance to sideslip.
      Experiment results showed that 1) the shape of each single suction cup for the
      underwater application was identified; 2) the structure of the multiple-cup
      assembly affects the adsorption force and tolerance to sideslip. 

PMID- 25569978
TI  - Contactless operating table control based on 3D image processing.
AB  - Interaction with mobile consumer devices leads to a higher acceptance and
      affinity of persons to natural user interfaces and perceptional interaction
      possibilities. New interaction modalities become accessible and are capable to
      improve human machine interaction even in complex and high risk environments,
      like the operation room. Here, manifold medical disciplines cause a great variety
      of procedures and thus staff and equipment. One universal challenge is to meet
      the sterility requirements, for which common contact-afflicted remote interfaces
      always pose a potential risk causing a hazard for the process. The proposed
      operating table control system overcomes this process risk and thus improves the
      system usability significantly. The 3D sensor system, the Microsoft Kinect,
      captures the motion of the user, allowing a touchless manipulation of an
      operating table. Three gestures enable the user to select, activate and
      manipulate all segments of the motorised system in a safe and intuitive way. The
      gesture dynamics are synchronised with the table movement. In a usability study,
      15 participants evaluated the system with a system usability score by Broke of
      79. This states a high potential for implementation and acceptance in
      interventional environments. In the near future, even processes with higher risks
      could be controlled with the proposed interface, while interfaces become safer
      and more direct. 

PMID- 25569979
TI  - Design of a high-density multi-channel electrode for multi-structure parallel
      recordings in rodents.
AB  - In neurophysiology, investigating brain connectivity within and between different
      brain structures is of fundamental importance for understanding nervous system
      function and its relation to behavior. Yet, parallel recordings in multiple brain
      structures is highly challenging, especially in rodents, which are most commonly
      employed in neurophysiological research but rather small in size. In this study,
      the design and manufacturing of a high-density multi-channel electrode for
      chronic, multi-structure parallel recordings in rats is presented and exemplified
      with functional neuronal recordings from 128 recording channels, placed
      bilaterally in eight different brain structures, in an awake, freely moving
      animal. 

PMID- 25569980
TI  - Body machine interfaces for neuromotor rehabilitation: a case study.
AB  - High-level spinal cord injury (SCI) survivors face every day two related
      problems: recovering motor skills and regaining functional independence. Body
      machine interfaces (BoMIs) empower people with sever motor disabilities with the
      ability to control an external device, but they also offer the opportunity to
      focus concurrently on achieving rehabilitative goals. In this study we developed
      a portable, and low-cost BoMI that addresses both problems. The BoMI remaps the
      user's residual upper body mobility to the two coordinates of a cursor on a
      computer monitor. By controlling the cursor, the user can perform functional
      tasks, such as entering text and playing games. This framework also allows the
      mapping between the body and the cursor space to be modified, gradually
      challenging the user to exercise more impaired movements. With this approach, we
      were able to change the behavior of our SCI subject, who initially used almost
      exclusively his less impaired degrees of freedom - on the left side - for
      controlling the BoMI. At the end of the few practice sessions he had restored
      symmetry between left and right side of the body, with an increase of mobility
      and strength of all the degrees of freedom involved in the control of the
      interface. This is the first proof of concept that our BoMI can be used to
      control assistive devices and reach specific rehabilitative goals simultaneously.

PMID- 25569981
TI  - Voltage-sensitive dye imaging of the visual cortices responding to electrical
      pulses at different intervals in mice in vivo.
AB  - Properties of the neural responses to electrical stimulus pulses delivered at
      various inter-pulse intervals were examined in the visual cortices of mice in
      vivo, with utilizing the voltage-sensitive dye imaging technique. Our
      experimental results provided the relationships between the inter-pulse intervals
      and the stimulus-evoked transient depolarizations, which may offer insight into
      the design of effective and efficient stimulation for cortical visual prostheses.

PMID- 25569982
TI  - Modeling transcranial electric stimulation in mouse: a high resolution finite
      element study.
AB  - Mouse models are widely used in studies of various forms of transcranial electric
      stimulation (TES). However, there is limited knowledge of the electric field
      distribution induced by TES in mice, and computational models to estimate this
      distribution are lacking. This study examines the electric field and current
      density distribution in the mouse brain induced by TES. We created a high
      resolution finite element mouse model incorporating ear clip electrodes commonly
      used in mouse TES to study, for example, electroconvulsive therapy (ECT). The
      electric field strength and current density induced by an ear clip electrode
      configuration were computed in the anatomically realistic, inhomogenous mouse
      model. The results show that the median electric field strength induced in the
      brain at 1 mA of stimulus current is 5.57 V/m, and the strongest field of 20.19
      V/m was observed in the cerebellum. Therefore, to match the median electric field
      in human ECT at 800 mA current, the electrode current in mouse should be set to
      approximately 15 mA. However, the location of the strongest electric field in
      posterior brain regions in the mouse does not model well human ECT which targets
      more frontal regions. Therefore, the ear clip electrode configuration may not be
      a good model of human ECT. Using high-resolution realistic models for simulating
      TES in mice may guide the establishment of appropriate stimulation parameters for
      future in vivo studies. 

PMID- 25569983
TI  - Stimulation strength and focality of electroconvulsive therapy and magnetic
      seizure therapy in a realistic head model.
AB  - This study examines the characteristics of the electric field (E-field) induced
      in the brain by electroconvulsive therapy (ECT) and magnetic seizure therapy
      (MST). The electric field induced by five ECT electrode configurations
      (bilateral, bifrontal, right unilateral, focal electrically administered seizure
      therapy, and frontomedial) as well as an MST coil configuration (circular) was
      computed in an anatomically realistic finite element model of the human head. We
      computed the maps of the electric field strength relative to an estimated neural
      activation threshold, and used them to evaluate the stimulation strength and
      focality of the various ECT and MST paradigms. The results show that the median
      ECT stimulation strength in the brain is 3-11 times higher than that for MST, and
      that the stimulated brain volume is substantially higher with ECT (47-100%) than
      with MST (21%). Our study provides insight into the observed reduction of
      cognitive side effects in MST compared to ECT, and supports arguments for
      lowering ECT current amplitude as a means of curbing its side effects. 

PMID- 25569984
TI  - Time-varying pulse trains limit retinal desensitization caused by continuous
      electrical stimulation.
AB  - An epiretinal prosthesis aims to restore functional vision in patients suffering
      from retinal degeneration caused by diseases such as Retinitis Pigmentosa (RP)
      and Age-Related Macular Degeneration (AMD). These diseases result in the loss of
      photoreceptors but bipolar, amacrine and ganglion cells survive at high rates and
      can be electrically activate to produce the sensation of light. Continuous
      application of biphasic stimulus pulses results in desensitization of the retina.
      In humans, this manifests as decreased brightness and increased stimulus
      thresholds. This study presents an in vivo model of retinal desensitization
      caused by continuous electrical stimulation and describes a novel stimulation
      pattern that limit desensitization. 

PMID- 25569985
TI  - Morphological and electrochemical properties of an explanted PtIr electrode array
      after 15 months in vivo.
AB  - We investigated the morphological and electrochemical properties of an explanted
      laser-machined 32 channel electrocorticogram (ECoG) electrode array made of
      platinum-iridium and silicone rubber. It was connected to a wireless brain
      computer interface (BCI) and implanted in a sheep for more than 15 months.
      Recordings and stimulations of cortical activity were conducted over the whole
      period on a regularly basis. Currently, this is the longest in vivo study for
      this type of ECoG electrode array. Results were compared with an unused electrode
      array of same dimensions, material and production method. Visual inspections
      revealed no significant material alterations, despite organic residuals which
      could be easily removed though. Electrochemical impedance measurements also
      attested proper long-term stability of magnitude and phase, the difference
      between explanted electrode contacts and those of the unused array were found
      negligible. 

PMID- 25569986
TI  - Decellular biological scaffold polymerized with PEDOT for improving peripheral
      nerve interface charge transfer.
AB  - Regenerative peripheral nerve interfaces (RPNIs) are for signal transfer between
      peripheral nerves inside the body to controllers for motorized prosthetics
      external to the body. Within the residual limb of an amputee, surgical
      construction of a RPNI connects a remaining peripheral nerve and spare muscle.
      Nerve signals become concentrated within the RPNI. Currently metal electrodes
      implanted on the RPNI muscle transfer signals but scarring around metal
      electrodes progressively diminishes charge transfer. Engineered materials may
      benefit RPNI signal transfer across the neural interface if they lower the power
      and charge density of the biologically meaningful signals. Poly3,4
      ethylenedioxythiophene (PEDOT) is known to mediate ionic potentials allowing
      excitation across a critical nerve gap. We hypothesize that the capacity of an
      interface material to conduct electron mediated current is significantly
      increased by polymerized coating of PEDOT. SIS was either used plain or after
      PEDOT coating by electrochemical polymerization. Muscle forces are a direct
      representation of stimulating current distribution within an RPNI. In situ muscle
      forces were measured for the same muscle by electrically stimulating: a) the
      muscle's innervating nerve, b) directly on the muscle, c) on plain SIS laid on
      the muscle, and d) on SIS polymerized with PEDOT laid on the muscle. Electro
      chemically coating PEDOT on SIS resulted in a thin, flexible material. PEDOT
      coated SIS distributed electrical stimulation more efficiently than SIS alone.
      Conductive polymer containing biological material allowed ionic signal
      distribution within the RPNI like muscle at lower charge density. 

PMID- 25569987
TI  - Wireless simultaneous stimulation-and-recording device to train cortical circuits
      in somatosensory cortex.
AB  - We describe for the first time the design, implementation, and testing of a
      telemetry controlled simultaneous stimulation and recording device (SRD) to
      deliver chronic intercortical microstimulation (ICMS) to physiologically
      identified sites in rat somatosensory cortex (SI) and test hypotheses that
      chronic ICMS strengthens interhemispheric pathways and leads to functional
      reorganization in the enhanced cortex. The SRD is a custom embedded device that
      uses the Cypress Semiconductor's programmable system on a chip (PSoC) that is
      remotely controlled via Bluetooth. The SRC can record single or multiunit
      responses from any two of 12 available inputs at 1-15 ksps per channel and
      simultaneously deliver stimulus pulses (0-255 MUA; 10 V compliance) to two user
      selectable electrodes using monophasic, biphasic, or pseudophasic stimulation
      waveforms (duration: 0-5 ms, inter-phase interval: 0-5 ms, frequency: 0.1-5 s,
      delay: 0-10 ms). The SRD was bench tested and validated in vivo in a rat animal
      model. 

PMID- 25569988
TI  - KDI: a wireless power-efficient modular platform for pre-clinical evaluation of
      implantable neural recording designs.
AB  - This paper presents a power-efficient modular wireless platform which has been
      designed for prototyping and pre-clinical evaluations of neural recording
      implants. This Kit for Designing Implants (KDI) is separated in function specific
      modules of 34*34mm which can be assembled as needed. Five modules have been
      designed and optimized for ultra-low power consumption and a protective casing
      has been designed for pre-clinical trials. Two different wireless modules have
      been compared and the KDI performances have been evaluated in terms of
      modularity, wireless throughput and power consumption. 

PMID- 25569989
TI  - Device for the implantation of neural electrode arrays.
AB  - Electrode arrays used in neural recording and stimulation applications must be
      implanted carefully to minimize damage to the underlying tissue. A device has
      been designed to improve a surgeon's control over implantation parameters
      including depth, insertion velocity, and insertion force. The device has been
      designed to operate without contacting tissue and to respond to tissue movements
      in real time during insertion. This device uses an electrical motor to drive
      electrode arrays into tissue and allows for the monitoring of and response to
      electrode depth during insertion. A prototype device has been constructed and
      tests have been performed to determine the velocity and force characteristics of
      the motor when inside the device housing. Future versions of the device will use
      a custom-designed motor with longer linear travel, which will allow the insertion
      device to be held farther from tissue while still ensuring proper array
      insertion. 

PMID- 25569990
TI  - Suitability of SU-8, EpoClad and EpoCore for flexible waveguides on implantable
      neural probes.
AB  - In neuroscience optogenetics was established as common research method. However,
      the devices used for opto-genetical stimulation, so called optrodes, are often
      made of stiff materials which lead to cell damage. We investigated the
      suitability of the epoxy based polymers SU-8, EpoClad and EpoCore for the
      fabrication of bendable thin-film waveguides. With the integration of such
      waveguides into neural electrodes flexible optrodes could be realized which would
      allow simultaneous stimulation at different sites. Three different waveguide
      types were fabricated with SU-8 and EpoClad as cladding and EpoCore as core
      materials. The optical losses were measured from 12.9 dB (SU-8 and air cladding)
      over 14.4 dB (SU-8 cladding) to 22.4 dB (EpoClad cladding). Aging in air at 23 
      degrees C for a time period of 80 days led to a continuous increase of the
      losses, which seemed to adapt to an upper limit of over 20 dB. Samples aged in
      saline solution at 37  degrees C showed a faster increase in the first 20 days,
      but a similar upper limit. 

PMID- 25569991
TI  - Accelerated-stress reliability evaluation for an encapsulated wireless cortical
      stimulator.
AB  - In preparing a wireless cortical stimulator for use in the Intracortical Visual
      Prosthesis (ICVP) project at the Illinois Institute of Technology (IIT), an
      accelerated environmental stress test is being performed on prototype stimulator
      modules. Stimulator devices, containing a custom application specific integrated
      circuit (ASIC), and encapsulated with PDMS, were soaked in an autoclave chamber
      at 121 degrees C and 100% relative humidity for more than 2200 hours with and
      without power supplied to the ASIC. Experimental results showed no physical
      degradation of the stimulator devices after soaking. Reverse telemetry that
      measures the stimulator internal power supply, recorded periodically over the
      entire test time, verified that the devices were electrically functioning, as
      designed, without deterioration. Taking into consideration other standard
      reliability test environments, the accelerated moisture resistance-biased
      autoclave testing duration of 2200 hours, as conducted in this study, overwhelms
      other less-severe test conditions and demonstrates long term stability of the
      proposed vision prosthesis device with proven thermo-mechanical and electrical
      robustness. 

PMID- 25569992
TI  - Diffusion-bonded electrodes for chronic neural stimulation.
AB  - We report a novel method to fabricate chronic neural interfaces with the intent
      to combine the reliability and lifetime of bulk metal electrodes, with the
      miniaturization and mechanical flexibility of thin-film polymer microelectrode
      arrays. 10 MUm thick platinum discs were laser cut from a foil into the shape of
      individual electrodes, and coated with gold on the backside. The discs were
      bonded to a microelectrode array with gold bond pads via gold-gold inter
      diffusion using a flipchip bonder. Electrode bonding and adhesion was
      characterized using mechanical shear testing and electrical testing. Electrode
      performance was characterized in vitro using electrochemical impedance
      spectroscopy and cyclic voltammetry. Biphasic electrical pulsing experiments were
      conducted on the bonded electrodes to study degradation of the electrode; the
      preliminary results show that the electrodes can withstand at least 4,900 million
      pulses with no adverse electrochemical or visual degradation. Overall, this is a
      promising new method for fabricating chronic neural electrodes for stimulation or
      recording that combines the reliability of commercial bulk electrodes with the
      miniaturization and versatility of microfabricated technologies. 

PMID- 25569993
TI  - An implantable, miniaturized SU-8 optical probe for optogenetics-based deep brain
      stimulation.
AB  - This paper reports a method of making optical probes for optogenetics-based deep
      brain optical stimulation using SU-8, which effectively increases light coupling
      efficiency, has excellent mechanical stiffness, and reduces fabrication
      complexity. By mounting microscale LEDs (MULEDs) at the tip of a SU-8 probe and
      directly inserting the light source into deep brain regions, attenuation caused
      by light transmission in wave-guided structures such as optical fibers or
      optrodes can be minimized. Compared to silicon neural probes, SU-8 is more
      biocompatible and flexible, which can reduce brain damage. Parylene-C
      encapsulation can potentially improve the long-term biocompatibility and
      reliability of the device for chronic implantation. The functionality has been
      proven by clearly light-induced neural activity. 

PMID- 25569994
TI  - Simultaneous high-definition transcranial direct current stimulation of the motor
      cortex and motor imagery.
AB  - Transcranial direct current stimulation (tDCS) has been used to affect the
      excitability of neurons within the cerebral cortex. Improvements in motor
      learning have been found in multiple studies when tDCS was applied to the motor
      cortex during or before task learning is performed. The application of tDCS to
      motor imagery, a cognitive task showing activation in similar areas to motor
      execution, has resulted in differing effects based on the amplitude and duration
      of stimulation. We utilize high definition tDCS, a more spatially localized
      version of tDCS, to investigate the effect of anodal stimulation on human motor
      imagery performance. In parallel, we model this stimulation using a finite
      element model to calculate stimulation area and electrical field amplitude within
      the brain in the motor cortex and non-stimulated frontal and parietal regions.
      Overall, we found a delayed increase in resting baseline power 30 minutes post
      stimulation in both the right and left sensorimotor cortices which resulted in an
      increase in event-related desynchronization. 

PMID- 25569995
TI  - Applying Time-sharing technique in a multimodal compact low-power CMOS neurochip
      for simultaneous neurochemical and action potential recording.
AB  - Brain is an electrochemical system and recent studies suggest simultaneous
      measurement of interrelated brain's electrical and neurochemical activity may
      lead to better understanding of brain function in addition to developing optimal
      neural prosthetics. By exploiting opamp Time-sharing technique to minimized power
      dissipation and silicon area, we have fabricated a power efficient implantable
      CMOS microsystem for simultaneous measurement of Action Potential (AP) and
      neurotransmitter concentration. Both AP-recording and neurotransmitter sensing
      subsystems share a single 653 nW amplifier which senses picoscale to microscale
      current that corresponds to micromolar neurotransmitter concentration and
      microscale AP voltage. This microsystem is fabricated in CMOS 0.18 MUm technology
      and tested using recorded signals from dorsal premotor cortex (PMd) area of a
      macaque monkey in our lab. 

PMID- 25569996
TI  - Dynamic spike threshold and nonlinear dendritic computation for coincidence
      detection in neuromorphic circuits.
AB  - We present an electronic cortical neuron incorporating dynamic spike threshold
      and active dendritic properties. The circuit is simulated using a carbon nanotube
      field-effect transistor SPICE model. We demonstrate that our neuron has lower
      spike threshold for coincident synaptic inputs; however when the synaptic inputs
      are not in synchrony, it requires larger depolarization to evoke the neuron to
      fire. We also demonstrate that a dendritic spike is key to precisely-timed input
      output transformation, produces reliable firing and results in more resilience to
      input jitter within an individual neuron. 

PMID- 25569997
TI  - The effect of site placement within silicon microelectrodes on the long-term
      electrophysiological recordings.
AB  - Intracortical microelectrodes can be used to treat various neurological disorders
      given their capabilities to interface with single or multiple populations of
      neurons. However, most of these penetrating devices have been reported to fail
      over time, within weeks to months, putatively due to the foreign body response
      (FBR) which persistently aggravates the surrounding brain tissues. A number of
      studies have confirmed that various electrode properties, such as size, shape,
      and surface area, may play a role in the biological responses to the
      microelectrode. Further experimental data is needed to determine the effect of
      these properties on the FBR and the recording performance. In this paper, we
      evaluate the effect of site placement using Michigan arrays with sites on the
      center, edge, and tip of the shank. The results show that there is significant
      performance variance between the center, edge, and tip sites. 

PMID- 25569998
TI  - Effects of carbon nanotube and conducting polymer coated microelectrodes on
      single-unit recordings in vitro.
AB  - Neuronal networks cultured on microelectrode arrays (MEAs) have been utilized as
      biosensors that can detect all or nothing extracellular action potentials, or
      spikes. Coating the microelectrodes with carbon nanotubes (CNTs), either pristine
      or conjugated with a conductive polymer, has been previously reported to improve
      extracellular recordings presumably via reduction in microelectrode impedance.
      The goal of this work was to examine the basis of such improvement in vitro.
      Every other microelectrode of in vitro MEAs was electrochemically modified with
      either conducting polymer, poly-3,4-ethylenedioxythiophene (PEDOT) or a blend of
      CNT and PEDOT. Mouse cortical tissue was dissociated and cultured on the MEAs to
      form functional neuronal networks. The performance of the modified and unmodified
      microelectrodes was evaluated by activity measures such as spike rate, spike
      amplitude, burst duration and burst rate. We observed that the yield, defined as
      percentage of microelectrodes with neuronal activity, was significantly higher by
      55% for modified microelectrodes compared to the unmodified sites. However, the
      spike rate and burst parameters were similar for modified and unmodified
      microelectrodes suggesting that neuronal networks were not physiologically
      altered by presence of PEDOT or PEDOT-CNT. Our observations from
      immunocytochemistry indicated that neuronal cells were more abundant in proximity
      to modified microelectrodes. 

PMID- 25569999
TI  - Bio-impedance characterization technique with implantable neural stimulator using
      biphasic current stimulus.
AB  - Knowledge of the bio-impedance and its equivalent circuit model at the electrode
      electrolyte/tissue interface is important in the application of functional
      electrical stimulation. Impedance can be used as a merit to evaluate the
      proximity between electrodes and targeted tissues. Understanding the equivalent
      circuit parameters of the electrode can further be leveraged to set a safe
      boundary for stimulus parameters in order not to exceed the water window of
      electrodes. In this paper, we present an impedance characterization technique and
      implement a proof-of-concept system using an implantable neural stimulator and an
      off-the-shelf microcontroller. The proposed technique yields the parameters of
      the equivalent circuit of an electrode through large signal analysis by injecting
      a single low-intensity biphasic current stimulus with deliberately inserted inter
      pulse delay and by acquiring the transient electrode voltage at three well
      specified timings. Using low-intensity stimulus allows the derivation of
      electrode double layer capacitance since capacitive charge-injection dominates
      when electrode overpotential is small. Insertion of the inter-pulse delay creates
      a controlled discharge time to estimate the Faradic resistance. The proposed
      method has been validated by measuring the impedance of a) an emulated Randles
      cells made of discrete circuit components and b) a custom-made platinum electrode
      array in-vitro, and comparing estimated parameters with the results derived from
      an impedance analyzer. The proposed technique can be integrated into implantable
      or commercial neural stimulator system at low extra power consumption, low extra
      hardware cost, and light computation. 

PMID- 25570000
TI  - Fabrication and electrochemical comparison of SIROF-AIROF-EIROF microelectrodes
      for neural interfaces.
AB  - Iridium oxide has been widely used in neural recording and stimulation due to its
      good stability and large charge storage capacity (CSC). In general, the iridium
      oxide film used in the electrophysiological application can be grouped into three
      principal classifications: sputtering iridium oxide film (SIROF), activated
      iridium oxide film (AIROF) and electrodeposited iridium oxide film (EIROF).
      Although these kinds of iridium oxide all can remarkably reduce the impedance and
      increase the CSC of the microelectrode, they also exhibit markedly differences in
      electrochemical performances. After activation, the CSC of EIROF is 68.20
      mC/cm(2), which is 88.7 % larger than that of the SIROF and 67.6 % larger than
      that of the AIROF. The impedance at 1 kHz of the three kinds of iridium oxide
      microelectrode is around 4000 ohm, it is acceptable for the neural interface
      application. The phase at 1 kHz of the AIROF microelectrode is the largest which
      is -6.1 degree, about 22.6 % of the SIROF and 44.5 % of the EIROF. 

PMID- 25570001
TI  - Printable and transparent micro-electrocorticography (MUECoG) for optogenetic
      applications.
AB  - Micro-electrocorticography (MUECoG) displays advantages over traditional invasive
      methods. The MUECoG electrode can record neural activity with high spatial
      temporal resolution and it can reduce implantation side effects (e.g. vascular
      and local-neuronal damage, tissue encapsulation, infection). In this study, we
      propose a printable transparent MUECoG electrode for optogenetic applications by
      using ultrasonic microfluid printing technique. The device is based on poly(3,4
      ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) as a conductive
      polymer, polydimethylsiloxane (PDMS) as an insulating polymer and poly(chloro
      para-xylylene) (Parylene-C) as the device substrate. We focus on ultrasonic
      microfluid printing due to its low production cost, excellent material handling
      capability, and its customizable film thickness (down to 5-20 microns). The
      ultrasonic fluid-printed MUECoG displays high spatial resolution and records
      simulated signal (0-200 Hz sine wave) effectively with low electrode impedance
      (50-200 kOhms@1kHz). The MUECoG also shows good biocompatibility suitable for
      customizable chronic implants. This new neural interfacing device could be
      combined with optogenetics and Brain-Computer Interface (BCI) applications for a
      possible future use in neurological disease diagnosis and rehabilitations. 

PMID- 25570002
TI  - Towards a miniaturized brain-machine-spinal cord interface (BMSI) for restoration
      of function after spinal cord injury.
AB  - Nearly 6 million people in the United States are currently living with paralysis
      in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized
      closed-loop neural interfaces have the potential for restoring function and
      mobility lost to debilitating neural injuries such as SCI by leveraging recent
      advancements in bioelectronics and a better understanding of the processes that
      underlie functional and anatomical reorganization in an injured nervous system.
      This paper describes our current progress towards developing a miniaturized brain
      machine-spinal cord interface (BMSI) that is envisioned to convert in real time
      the neural command signals recorded from the brain to electrical stimuli
      delivered to the spinal cord below the injury level. Specifically, the paper
      reports on a corticospinal interface integrated circuit (IC) as a core building
      block for such a BMSI that is capable of low-noise recording of extracellular
      neural spikes from the cerebral cortex as well as muscle activation using
      intraspinal microstimulation (ISMS) in a rat with contusion injury to the
      thoracic spinal cord. The paper further presents results from a neurobiological
      study conducted in both normal and SCI rats to investigate the effect of various
      ISMS parameters on movement thresholds in the rat hindlimb. Coupled with proper
      signal-processing algorithms in the future for the transformation between the
      cortically recorded data and ISMS parameters, such a BMSI has the potential to
      facilitate functional recovery after an SCI by re-establishing corticospinal
      communication channels lost due to the injury. 

PMID- 25570003
TI  - Augmented reality system for freehand guide of magnetic endovascular devices.
AB  - Magnetic guide of endovascular devices or magnetized therapeutic microparticles
      to the specific target in the arterial tree is increasingly studied, since it
      could improve treatment efficacy and reduce side effects. Most proposed systems
      use external permanent magnets attached to robotic manipulators or magnetic
      resonance imaging (MRI) systems to guide internal carriers to the region of
      treatment. We aim to simplify this type of procedures, avoiding or reducing the
      need of robotic arms and MRI systems in the surgical scenario. On account of this
      we investigated the use of a wearable stereoscopic video see-through augmented
      reality system to show the hidden vessel to the surgeon; in this way, the surgeon
      is able to freely move the external magnet, following the showed path, to lead
      the endovascular magnetic device towards the desired position. In this
      preliminary study, we investigated the feasibility of such an approach trying to
      guide a magnetic capsule inside a vascular mannequin. The high rate of success
      and the positive evaluation provided by the operators represent a good starting
      point for further developments of the system. 

PMID- 25570004
TI  - Three-dimensional reconstruction and surface extraction of lower limbs as
      visualization methodologies of ecchymosis.
AB  - This paper presents a computational system for three-dimensional reconstruction
      and surface extraction of the human lower limb as a new methodology of
      visualizing images of multifaceted ecchymosis on the lower limbs. Through
      standardization of image acquisition by a mechanical system, an algorithm was
      developed for three-dimensional and surface reconstruction based on the
      extraction of depth from silhouettes. In order to validate this work, a three
      dimensional model of the human lower limb was used inside a virtual environment.
      At this environment the mechanical procedure of image acquisition was simulated,
      resulting in 100 images which was later submitted to all algorithms developed. It
      was observed that the systems for three-dimensional reconstruction and surface
      extraction of the object were able to generate a new visualization method of the
      lesion. The results allow us to conclude that the developed systems provided
      adequate three-dimensional and two-dimensional visualization of the surface of
      the simulated model. Despite the lack of experiments with real ecchymoses, the
      systems developed in this work show great potential to be included in the
      standard methods for the visualization of ecchymoses. 

PMID- 25570005
TI  - A PC-based laparoscopic surgery skills training and assessment system.
AB  - The purpose of this study is to build a cost-effective and easy-to-popularize
      laparoscopic training system based on improving traditional training box. The
      system has the capability of objective skills assessment and the function of
      automatic recording of training process and results, as well as 3-dimensional
      coordinate tracking of instruments. The results of pilot experiment in
      laparoscopic-assisted grip skill assessment had been shown the system can assess
      the different grip ability level between the senior surgeons and junior
      residents. Regarding to the evaluation of training effectiveness, five subjects
      without laparoscopic surgery experiences were asked to perform grip training for
      five days to observe their training curves. According to the experimental
      results, the total time taken for subject 1 to subject 5 are improved by 54.9%,
      52.0%, 60.6%, 23.3%, and 63.5% separately. 

PMID- 25570006
TI  - BRAIN initiative: transcranial magnetic stimulation automation and calibration.
AB  - In this paper, we introduced an automated TMS system with robot control and
      optical sensor combined with neuronavigation software. By using the robot, the
      TMS coil can be accurately positioned over any preselected brain region. The
      neuronavigation system provides an accurate positioning of a magnetic coil in
      order to induce a specific cortical excitation. An infrared optical measurement
      device is also used in order to detect and compensate for head movements of the
      patient. This procedure was simulated using a PC based robotic simulation
      program. The proposed automated robot system is integrated with TMS numerical
      solver and allows users to actually see the depth, location, and shape of the
      induced eddy current on the computer monitor. 

PMID- 25570007
TI  - Artificial muscles for a novel simulator in minimally invasive spine surgery.
AB  - Vertebroplasty and kyphoplasty are commonly used minimally invasive methods to
      treat vertebral compression fractures. Novice surgeons gather surgical skills in
      different ways, mainly by "learning by doing" or training on models, specimens or
      simulators. Currently, a new training modality, an augmented reality simulator
      for minimally invasive spine surgeries, is going to be developed. An important
      step in investigating this simulator is the accurate establishment of artificial
      tissues. Especially vertebrae and muscles, reproducing a comparable haptical
      feedback during tool insertion, are necessary. Two artificial tissues were
      developed to imitate natural muscle tissue. The axial insertion force was used as
      validation parameter. It appropriates the mechanical properties of artificial and
      natural muscles. Validation was performed on insertion measurement data from
      fifteen artificial muscle tissues compared to human muscles measurement data.
      Based on the resulting forces during needle insertion into human muscles, a
      suitable material composition for manufacturing artificial muscles was found. 

PMID- 25570008
TI  - Simulation-based optimization of a near-infrared spectroscopic subcutaneous fat
      thickness measuring device.
AB  - Using Monte Carlo simulations we optimized the wavelength and source-detector
      distance (SDD) of a reflectance-based spectroscopic device used for measuring
      subcutaneous fat thickness. As the optical properties of muscle, fat and dermis
      are wavelength dependent, it is necessary to choose a wavelength that is highly
      sensitive to fat but insensitive to water and melanin. The SDD is important since
      it determines average photon penetration depth. With a tissue optics plug-in for
      the GEANT4/GAMOS system and published ex vivo tissue optical properties we were
      able to predict the behavior of different device configurations when used with
      varying thicknesses of fat, melanin concentrations or hydration levels. Our
      results indicate that the ideal wavelengths for fat measurement are 630-650 nm
      with an SDD of 2.6-29 cm. We also examined the potential of using near infrared
      (NIR) spectroscopy to determine tissue hydration levels, but concluded that this
      wavelength range was not ideal. 

PMID- 25570009
TI  - The effect of profound dehydration on electrical impedance of mouseskeletal
      muscle.
AB  - To determine if electrical impedance myography (EIM) technique can still be used
      safely to monitor muscle in cases of severe dehydration, we measured the
      electrical impedance at 1 kHz-1 MHz (37 frequencies) of n=8 wild type mice during
      48 h of fluid deprivation and compared to the results of n=8 mice that were
      provided with water ad libitum. Based on the relative change in the R0 (8%
      p=0.59) parameter from the Cole impedance model, there is a nonsignificant change
      in regard to the muscle extracellular fluid when compared to the relative change
      of body weight and body water loss (19.6% p<;0.0001 and 26.1% p<;0.0001
      respectively). The negligible changes of the phase at 50 kHz (1% p=0.88) confirm
      both the muscle fibers structural integrity and viability remained intact for
      that period of time. Accordingly, EIM can still be used to determine the status
      of muscle even during profound dehydration. 

PMID- 25570010
TI  - Development of Automatic Manipulation Device for Acupuncture (AMDA).
AB  - Needle lifting and thrusting manipulation is one of common skills in acupuncture.
      However, there exists artificial error in frequency and amplitude due to
      individual difference when performing lifting and thrusting during acupuncture.
      For providing stable and quantified effects and higher frequency when doing
      lifting and thrusting manipulation, a well controlled device is needed. The aim
      of this article is to report the preliminary results of the development of Auto
      Manipulation Device for Acupuncture (AMDA) and characterization of its functional
      parameters. A tissue-simulating Agar gel phantom with 4.8%, 5.2%, and 5.4%
      concentrations was prepared and used for characterization of the AMDA. Tests of
      the linearity, reliability and safety of the AMDA were implemented with
      conditions of different drive voltages, frequencies, and simulated tissues. Our
      preliminary results have demonstrated the developed AMDA its plausibility in the
      clinical application of acupuncture. 

PMID- 25570011
TI  - Target coverage and selectivity in field steering brain stimulation.
AB  - Deep Brain Stimulation (DBS) is an established treatment in Parkinson's Disease.
      The target area is defined based on the state and brain anatomy of the patient.
      The stimulation delivered via state-of-the-art DBS leads that are currently in
      clinical use is difficult to individualize to the patient particularities.
      Furthermore, the electric field generated by such a lead has a limited
      selectivity, resulting in stimulation of areas adjacent to the target and thus
      causing undesirable side effects. The goal of this study is, using actual
      clinical data, to compare in silico the stimulation performance of a symmetrical
      generic lead to a more versatile and adaptable one allowing, in particular, for
      asymmetric stimulation. The fraction of the volume of activated tissue in the
      target area and the fraction of the stimulation field that spreads beyond it are
      computed for a clinical data set of patients in order to quantify the lead
      performance. The obtained results suggest that using more versatile DBS leads
      might reduce the stimulation area beyond the target and thus lessen side effects
      for the same achieved therapeutical effect. 

PMID- 25570012
TI  - Influence of Vagus Nerve Stimulation parameters on chronotropism and inotropism
      in heart failure.
AB  - Vagus Nerve Stimulation (VNS) has been shown to be useful in heart failure
      patients, including antiarrhythmic effects, improvement of cardiac function and
      reduction of the mortality. However, the optimal configuration of VNS can be a
      difficult task, since there are several adjustable parameters, such as current
      amplitude (mA), pulse width (ms), burst frequency (Hz), number of pulses and, in
      the case of cardiac-triggered VNS, the delay (ms) between the R-wave and the
      beginning of the stimulation. The objective of this paper is to analyse the
      effect of these parameters, and their interaction, on the chronotropic and
      inotropic responses to vagal stimulation. 306 VNS sequences were tested on 12
      sheep with induced heart failure. Autonomic markers of the chronotropic (changes
      in RR interval) and inotropic (changes in dP/dtmax) effects were extracted from
      the observed data. In order to analyse the influence of stimulation parameters on
      these markers, a sensitivity analysis method was applied. Results illustrate the
      strong interaction between the delay and the others parameters. The number of
      pulses, the current and the frequency seem to be particularly influent on
      chronotropism and inotropism although the effect of the frequency is highly non
      linear or it depends on other parameters. 

PMID- 25570013
TI  - Efficacy of cathodal transcranial direct current stimulation in drug-resistant
      epilepsy: a proof of principle.
AB  - It has been proved that Transcranial DCS (tDCS) can modulate cortical
      excitability, enhancing or decreasing, respectively by anodal or cathodal
      polarity. The short-term and lasting alterations induced by tDCS are strictly
      related to the charge density, duration of stimulation and the depth of neuron
      below the skull. Epilepsy represents a pathophysiological model of unbalanced
      relation between cortical excitation and inhibition. In this line, tDCS can be
      exploited to counterbalance the neuronal hyper-excitation through electric neural
      modulation. This paper aims at providing the efficacy of cathodal tDCS in
      reducing seizures' frequency in drug-resistant focal epilepsy. The study was
      single blind and sham-controlled with an observation period of one month during
      which the patients or the caregivers provided a detailed seizures' calendar
      (frequency as n degrees /week; basal, post sham and post tDCS). Patients received
      sham or real tDCS treatment on the 8th and 22th days. Two patients affected by
      focal resistant epilepsy were enrolled. They both underwent a consistent
      reduction of the seizures'frequency: about 70 % for Patient 1 and about 50% for
      Patient 2. This study represents the proof that cathodal tDCS may be efficient in
      reducing seizures'frequency in focal resistant epilepsy. 

PMID- 25570014
TI  - ABrIL - Advanced Brain Imaging Lab : a cloud based computation environment for
      cooperative neuroimaging projects.
AB  - Neuroscience is an increasingly multidisciplinary and highly cooperative field
      where neuroimaging plays an important role. Neuroimaging rapid evolution is
      demanding for a growing number of computing resources and skills that need to be
      put in place at every lab. Typically each group tries to setup their own servers
      and workstations to support their neuroimaging needs, having to learn from
      Operating System management to specific neuroscience software tools details
      before any results can be obtained from each setup. This setup and learning
      process is replicated in every lab, even if a strong collaboration among several
      groups is going on. In this paper we present a new cloud service model - Brain
      Imaging Application as a Service (BiAaaS) - and one of its implementation -
      Advanced Brain Imaging Lab (ABrIL) - in the form of an ubiquitous virtual desktop
      remote infrastructure that offers a set of neuroimaging computational services in
      an interactive neuroscientist-friendly graphical user interface (GUI). This
      remote desktop has been used for several multi-institution cooperative projects
      with different neuroscience objectives that already achieved important results,
      such as the contribution to a high impact paper published in the January issue of
      the Neuroimage journal. The ABrIL system has shown its applicability in several
      neuroscience projects with a relatively low-cost, promoting truly collaborative
      actions and speeding up project results and their clinical applicability. 

PMID- 25570015
TI  - Optimization of multiple coils immersed in a conducting liquid for half
      hemisphere or whole-brain deep transcranial magnetic stimulation: a simulation
      study.
AB  - Transcranial magnetic stimulation (TMS) was proposed in 1985. Nevertheless, its
      wider use in the treatment of several neurologic diseases has been hindered by
      its inability to stimulate deep-brain regions. This is mainly due to the physical
      limiting effect arising from the presence of surface discontinuities,
      particularly between the scalp and air. Here, we present the optimization of a
      system of large multiple coils for whole-brain and half-hemisphere deep TMS,
      termed orthogonal configuration. COMSOL((r))-based simulations show that the
      system is capable of reaching the very center of a spherical brain phantom with
      58% induction relative to surface maximum. Such penetration capability surpasses
      to the best of our knowledge that of existing state of the art TMS systems. This
      induction capability strongly relies on the immersion of the stimulating coils
      and part of the head of the patient in a conducting liquid (e.g. simple saline
      solution). We show the impact of the presence of this surrounding conducting
      liquid by comparing the performance of our system with and without such liquid.
      In addition, we also compare the performance of the proposed coil with that of a
      circular coil, a figure-eight coil, and the H-coil. Finally, in addition to its
      whole-brain stimulation capability (e.g. potentially useful for prophylaxis of
      epileptic patients) the system is also able to stimulate mainly one brain
      hemisphere, which may be useful in stroke rehabilitation, among other
      applications. 

PMID- 25570016
TI  - Different layer thickness influences of a 50MHz intravascular ultrasound
      transducer.
AB  - In order to design a 50MHz intravascular ultrasound (IVUS) transducer with good
      pulse-echo responses, in this paper, a finite element model (FEM) was built to
      simulate the transducer acoustic performances with different layer thicknesses.
      According to comparisons of the acoustic fields and the admittance curves, the
      optimum thickness parameters are gained. And then, an IVUS PZT transducer with
      controlled layer thicknesses was fabricated and tested. The results of pulse-echo
      response tests shown this transducer with the optimum parameters had very good
      performance. The central frequency is 45.5MHz and its bandwidth was about 50%
      which are suitable for intravascular imaging. 

PMID- 25570018
TI  - Design of micromachined self-focusing piezoelectric composite ultrasound
      transducer.
AB  - Based on the Fresnel half-wave band interference, a micromachined self-focusing
      piezoelectric composite ultrasound transducer was proposed in this paper. The
      theoretical analysis was deduced based on the concept of constructive
      interference of acoustic waves and electromechanical response of piezoelectric
      composites. The calculated and simulation results showed that it combined the
      advantages of composite transducer and plate self-focusing transducer, and can
      achieve high electromechanical coupling coefficient, low acoustic impedance, high
      intensity, short focal length and micro size. Because it was based on the micro
      electromechanical systems, the fabrication process was accurate and controllable,
      which made it have good potential for interventional ultrasound imaging, cellular
      microstructure imaging, skin cancer detection and industrial nondestructive
      testing applications. 

PMID- 25570017
TI  - Lower body reaction testing using ultrasonic motion capture.
AB  - This paper presents a lower body reaction test that utilizes a new portable ultra
      sound based motion capture system (MobiFit) combined with a synchronized visual
      stimulus. This novel system was tested first for criterion validity and agreement
      against a gold standard laboratory based optical motion capture system (CODA). It
      was subsequently tested in the field during Gaelic football (GAA) team gym
      sessions with 35 subjects to demonstrate its utility and versatility. The lower
      body reaction test itself is novel in that it can be applied to a gross motor
      task. During testing, participants had sensors attached to their lower limbs and
      trunk. The speed of movement for each sensor was monitored at 500Hz using the
      Mobifit motion capture system, and reaction time was measured as the elapsed time
      from the appearance of a green indicator on the screen to a sensor reaching a set
      threshold velocity as the participant raised the corresponding leg. Pearson's
      correlation coefficient tested criterion validity against the CODA system and
      Intra class correlation coefficients and Bland-Altman plots assessed agreement of
      velocity measures obtained from the MobiFit and CODA systems. Results indicate
      that the MobiFit system is an accurate device to assess lower body reaction time
      and has advantage over standard laboratory measures in terms of portability and
      ease of set-up. 

PMID- 25570019
TI  - Human Factors Engineering and testing for a wearable, long duration ultrasound
      system self-applied by an end user.
AB  - One of the major challenges in the design of a new class of medical device is
      ensuring that the device will have a safe and effective user interface for the
      intended users. Human Factors Engineering addresses these concerns through direct
      study of how a user interacts with newly designed devices with unique features.
      In this study, a novel long duration, low intensity therapeutic ultrasound device
      is tested by 20 end users representative of the intended user population. Over
      90% of users were able to operate the device successfully. The therapeutic
      ultrasound device was found to be reasonably safe and effective for the intended
      users, uses, and use environments. 

PMID- 25570020
TI  - Ultrasonic modeling and hydrophone measurements of dual divergent transducers for
      wearable therapeutic ultrasound device.
AB  - This paper models and experimentally measures the acoustic interference from two
      low intensity 3MHz continuous ultrasound transducers of the sam(r) wearable
      ultrasound device. Resulting data show that placement configuration, which
      dictates interference depth, and frequency phase variation are the main factors
      to acoustic pressure distribution. Mathematical analysis reveals that the
      acoustic pressure distribution from continuous ultrasound is modulated by near
      field variations at shallow tissue depths. This observation is useful in the
      application of sam(r) and in the further research of its therapeutic benefits. 

PMID- 25570021
TI  - Wearable depression monitoring system with heart-rate variability.
AB  - A wearable depression monitoring system is proposed with an application-specific
      system-on-chip (SoC) solution. The SoC is designed to accelerate the filtering
      and feature extraction of heart-rate variability (HRV) from the electrocardiogram
      (ECG). Thanks to the SoC solution and planar-fashionable circuit board (P-FCB),
      the monitoring system becomes a low-power wearable system. Its dimension is 14cm
      * 7cm with 5mm thickness covering the chest band for convenient usage. In
      addition, with 3.7V 500mAh battery, its lifetime is at least 10 hours. For user's
      convenience, the system is interfacing to smart phones through Bluetooth
      communication. With the features of the HRV and Beck depression inventory (BDI),
      the smart phone application trains and classifies the user's depression scale
      with 71% of accuracy. 

PMID- 25570022
TI  - An ambulatory sensor-based system for quantification of nighttime micturition for
      accurate nocturia assessment.
AB  - Nocturia is a widespread condition where patients need to micturate frequently
      during the nighttime. In order to define treatment and measure therapeutic
      success in nocturia, questionnaires are traditionally used for ambulatory
      assessment. However, questionnaires were reported to suffer from compliance,
      embarrassment and subjective bias. An automatic sensor-based system for
      quantification of nighttime micturition for accurate nocturia assessment would
      not suffer from these disadvantages, and its development was therefore the
      purpose of this study. We defined a sensor-based system for ambulatory use,
      consisting of a sensor watch and a room occupancy sensor. Using this system, we
      so far collected data from 6 participants and 82 nights in an ongoing study. We
      report the details of the system, as well as the data analysis. The system is
      very accurate, with an average misdetection rate of 0.32 and a mean absolute
      deviation of 3.8 % when comparing the average number of nighttime micturitions.
      This novel sensor-based nighttime micturition quantification system has the
      potential to be used as an objective ambulatory assessment tool for nocturia
      diagnosis and treatment. 

PMID- 25570023
TI  - A low-power fall detection algorithm based on triaxial acceleration and
      barometric pressure.
AB  - This paper proposes a low-power fall detection algorithm based on triaxial
      accelerometry and barometric pressure signals. The algorithm dynamically adjusts
      the sampling rate of an accelerometer and manages data transmission between
      sensors and a controller to reduce power consumption. The results of simulation
      show that the sensitivity and specificity of the proposed fall detection
      algorithm are both above 96% when applied to a previously collected dataset
      comprising 20 young actors performing a combination of simulated falls and
      activities of daily living. This level of performance can be achieved despite a
      10.9% reduction in power consumption. 

PMID- 25570024
TI  - Assessing the challenges of a pulse wave velocity based blood pressure
      measurement in surgical patients.
AB  - Development of a continuous noninvasive blood pressure (cNIBP) monitor that is
      unobtrusive to patients is an attractive alternative to the cuff based
      measurements performed on medical-surgical floors in the hospital. Pulse wave
      velocity (PWV) provides a means to continuously monitor blood pressure in these
      patients. However, a PWV based cNIBP monitor faces a number of challenges in
      order to accurately measure blood pressure. In our study, we investigated some of
      the challenges faced by a body-worn cNIBP monitor (i.e. ViSi Mobile) on data
      collected on patients undergoing surgery. Results indicated that 1) pulse arrival
      time (PAT) values from ViSi Mobile were well correlated with PAT values obtained
      from an invasive reference; 2) the reciprocal of the PAT measurements were
      linearly correlated with blood pressure but the calibration curve was altered by
      administration of certain vasoactive substances; and 3) there are deterministic
      correlations between systolic pressure, diastolic pressure and the corresponding
      mean arterial pressure over a wide range of blood pressure values. 

PMID- 25570025
TI  - Plantar pressure cartography reconstruction from 3 sensors.
AB  - Foot problem diagnosis is often made by using pressure mapping systems,
      unfortunately located and used in the laboratories. In the context of e-health
      and telemedicine for home monitoring of patients having foot problems, our focus
      is to present an acceptable system for daily use. We developed an ambulatory
      instrumented insole using 3 pressures sensors to visualize plantar pressure
      cartographies. We show that a standard insole with fixed sensor position could be
      used for different foot sizes. The results show an average error measured at each
      pixel of 0.01 daN, with a standard deviation of 0.005 daN. 

PMID- 25570026
TI  - Improved activity recognition via Kalman smoothing and multiclass linear
      discriminant analysis.
AB  - Improving activity recognition, with special focus on fall-detection, is the
      subject of this study. We show that Kalman smoothed in-painting of missing pose
      information and task-specific dimensionality reduction of activity feature
      vectors leads to significantly improved activity classification performance. We
      illustrate our findings by applying common classification algorithms to
      dimensionally reduced feature vectors, and compare our accuracy to previous work.
      In part two we investigate our methods on a small subset of the data, in order to
      ascertain what accuracy performance is achievable with the smallest amount of
      information available. 

PMID- 25570027
TI  - Monitoring activities of daily living based on wearable wireless body sensor
      network.
AB  - With recent advances in microprocessor chip technology, wireless communication,
      and biomedical engineering it is possible to develop miniaturized ubiquitous
      health monitoring devices that are capable of recording physiological and
      movement signals during daily life activities. The aim of the research is to
      implement and test the prototype of health monitoring system. The system consists
      of the body central unit with Bluetooth module and wearable sensors: the custom
      designed ECG sensor, the temperature sensor, the skin humidity sensor and
      accelerometers placed on the human body or integrated with clothes and a network
      gateway to forward data to a remote medical server. The system includes custom
      designed transmission protocol and remote web-based graphical user interface for
      remote real time data analysis. Experimental results for a group of humans who
      performed various activities (eg. working, running, etc.) showed maximum 5%
      absolute error compared to certified medical devices. The results are promising
      and indicate that developed wireless wearable monitoring system faces challenges
      of multi-sensor human health monitoring during performing daily activities and
      opens new opportunities in developing novel healthcare services. 

PMID- 25570028
TI  - A new smart fall-down detector for senior healthcare system using inertial
      microsensors.
AB  - A new smart fall-down detector for senior healthcare system using inertial
      microsensors and Wi-Fi technology has been designed, prototyped and characterized
      in this work. The detector can reduce the risk of severe injury or death caused
      by falling down with minimum false alarm rate. The different patterns of motion
      are sensed by a set of inertial sensors composed of a tri-axial accelerometer and
      a tri-axial gyroscope. The signals of motion are sampled and processed by a
      microcontroller with integrated algorithms. The smart algorithm integrated with
      machine learning can be customized according to different habits of different
      seniors to reduce false alarms. The fall-down signal is transmitted through Wi-Fi
      to the client via Internet. 

PMID- 25570029
TI  - Non-contact measurement of respiratory function and deduction of tidal volume.
AB  - This paper further the investigation of Doppler radar feasibility in measuring
      the flow in and out due to inhalation and exhalation under different conditions
      of breathing activities. Three different experiment conditions were designed to
      investigate the feasibility and consistency of Doppler radar which includes the
      combination of the states of normal breathing, deep breathing and apnoea state
      were demonstrated. The obtained Doppler radar signals were correlated and
      compared with the gold standard medical device, spirometer, yielding a good
      correlations between both devices. We also demonstrated the calibration of the
      Doppler radar signal can be performed in a simple manner in order to have a good
      agreements with the spirometer readings. The measurement of the flow in and out
      during the breathing activities can be measured accurately under different
      dynamics of breathing as long as the calibration is performed correctly. 

PMID- 25570030
TI  - Non-contact multi-radar smart probing of body orientation based on micro-Doppler
      signatures.
AB  - Micro-Doppler signatures carry useful information about body movements and have
      been widely applied to different applications such as human activity recognition
      and gait analysis. In this paper, micro-Doppler signatures are used to identify
      body orientation. Four AC-coupled continuous-wave (CW) smart radar sensors were
      used to form a multiple-radar network to carry out the experiments in this paper.
      162 tests were performed in total. The experiment results showed a 100% accuracy
      in recognizing eight body orientations, i.e., facing north, northeast, east,
      southeast, south, southwest, west, and northwest. 

PMID- 25570031
TI  - A method of ECG template extraction for biometrics applications.
AB  - ECG has attracted widespread attention as one of the most important non-invasive
      physiological signals in healthcare-system related biometrics for its
      characteristics like ease-of-monitoring, individual uniqueness as well as
      important clinical value. This study proposes a method of dynamic threshold
      setting to extract the most stable ECG waveform as the template for the
      consequent ECG identification process. With the proposed method, the accuracy of
      ECG biometrics using the dynamic time wraping for difference measures has been
      significantly improved. Analysis results with the self-built electrocardiogram
      database show that the deployment of the proposed method was able to reduce the
      half total error rate of the ECG biometric system from 3.35% to 1.45%. Its
      average running time on the platform of android mobile terminal was around 0.06
      seconds, and thus demonstrates acceptable real-time performance. 

PMID- 25570032
TI  - Mixed-signal VLSI independent component analyzer for hearing aid applications.
AB  - We present a mixed-signal architecture for implementation of independent
      component analysis designed for the task of blind source separation of acoustic
      sources interfacing miniature microphone array. The matrix-vector multiplication
      is implemented through integration of switched current sources controlled by the
      pulse-width modulated signals. The proposed architecture implementing 3*3 static
      ICA in 0.5MUm CMOS technology occupies chip area of 0.49 mm(2) with the power
      consumption of 80MUW at 5 V supply voltage. 

PMID- 25570033
TI  - Eye-tracking capabilities of low-cost EOG system.
AB  - This paper presents the design and implementation of a low-cost eye tracking
      system that allows measuring the rotational angle of the eye and gaze direction
      in healthy individuals. The system consists of an EOG circuit with simple
      components that acquire both horizontal and vertical eye movement through regular
      all-purpose contact electrodes. Then the data are analyzed and translated into
      corresponding angle values representing the eye rotation angle in both
      orientations. Results show that horizontal angle measurements are much more
      accurate than vertical measurements. A discussion regarding the performance and
      possible improvements is presented. 

PMID- 25570034
TI  - A portable heat flux sensor.
AB  - Nowadays monitoring physiological signals in real situations is essential to get
      the best diagnosis on patients. In this study we focus on the heat flux generated
      by the human body. We are developing a portable heat flux sensor using specific
      thermal materials. 

PMID- 25570035
TI  - Development of wearable sensors for tailored patient wound care.
AB  - In recent years a specialist interest has developed worldwide in advanced wound
      management for difficult to heal chronic wounds. Further progress in advanced
      wound management will require an improvement in personalized medicine for the
      patient and in particular an improvement in the availability of diagnostic tests
      and parameters that fulfil clinical need in wound management decisions. However,
      without easy to use sensors for nurses and carers these potentially important
      near-patient diagnostic parameters will not enter clinical diagnostics. This
      study focuses on a number of metrics for wound condition and wound healing: wound
      fluid pH, wound moisture, and wound matrix metalloproteinases (MMP) enzyme
      activity. To observe these important markers state of the art sensors have been
      developed that are based on inexpensive sensing technologies that can be
      integrated within wound dressings. These sensors will enable the wound healing
      markers to be studied and profiled in clinics which will further enhance the
      understanding of these markers and their relationship in the complex healing
      process involved in chronic wound healing. 

PMID- 25570036
TI  - A piezoelectric energy-harvesting shoe system for podiatric sensing.
AB  - This paper provides an energy-harvesting, shoe-mounted system for medical sensing
      using piezoelectric transducers for generating power. The electronics are
      integrated inside a conventional consumer shoe, measuring the pressure of the
      wearer's foot exerted on the sole at six locations. The electronics are
      completely powered by the harvested energy from walking or running, generating 10
      20 MUJ of energy per step that is then consumed by capturing and storing the
      force sensor data. The overall shoe system demonstrates that wearable sensor
      electronics can be adequately powered through piezoelectric energy-harvesting. 

PMID- 25570037
TI  - Feasibility of energy harvesting techniques for wearable medical devices.
AB  - Wearable devices are arguably one of the most rapidly growing technologies in the
      computing and health care industry. These systems provide improved means of
      monitoring health status of humans in real-time. In order to cope with continuous
      sensing and transmission of biological and health status data, it is desirable to
      move towards energy autonomous systems that can charge batteries using passive,
      ambient energy. This not only ensures uninterrupted data capturing, but could
      also eliminate the need to frequently remove, replace, and recharge batteries. To
      this end, energy harvesting is a promising area that can lead to extremely power
      efficient portable medical devices. This paper presents an experimental prototype
      to study the feasibility of harvesting two energy sources, solar and
      thermoelectric energy, in the context of wearable devices. Preliminary results
      show that such devices can be powered by transducing ambient energy that
      constantly surrounds us. 

PMID- 25570038
TI  - Implanted electronic siren to alarm for bladder full with urine.
AB  - A Device to detect for the bladder which is full with urine is designed. The
      device can measure bladder pressure. The pressure signals are processed. When the
      pressure exceeds 40cm water column, Pressure signal exceeds a fixed voltage. At
      the same time, Oscillator sends a signal and the signal transmits to the body
      surface. The receiver accepts the oscillating signal. Then, the alarm alerts.
      Liquid pressure sensor is used to measure bladder pressure. Signal transmits
      through a pig bladder to pigskin to verify the feasibility of the program. 

PMID- 25570039
TI  - A simple microbial fuel cell model for improvement of biomedical device powering
      times.
AB  - This study describes a Matlab based Microbial Fuel Cell (MFC) model for a
      suspended microbial population, in the anode chamber for the use of the MFC in
      powering biomedical devices. The model contains three main sections including
      microbial growth, microbial chemical uptake and secretion and electrochemical
      modeling. The microbial growth portion is based on a Continuously Stirred Tank
      Reactor (CSTR) model for the microbial growth with substrate and electron
      acceptors. Microbial stoichiometry is used to determine chemical concentrations
      and their rates of change and transfer within the MFC. These parameters are then
      used in the electrochemical modeling for calculating current, voltage and power.
      The model was tested for typically exhibited MFC characteristics including
      increased electrode distances and surface areas, overpotentials and operating
      temperatures. Implantable biomedical devices require long term powering which is
      the main objective for MFCs. Towards this end, our model was tested with
      different initial substrate and electron acceptor concentrations, revealing a
      four-fold increase in concentrations decreased the power output time by 50%.
      Additionally, the model also predicts that for a 35.7% decrease in specific
      growth rate, a 50% increase in power longevity is possible. 

PMID- 25570040
TI  - Miniaturizing RFID for magnamosis.
AB  - Anastomosis is a common surgical procedure using staples or sutures in an open or
      laparoscopic surgery. A more effective and much less invasive alternative is to
      apply the mechanical pressure on the tissue over a few days [1]. Since the
      pressure is produced by the attractive force between two permanent magnets, the
      procedure is called magnamosis[1]. To ensure the two magnets are perfectly
      aligned during the surgery, a miniaturized batteryless Radio Frequency
      IDentification (RFID) tag is developed to wirelessly telemeter the status of a
      pressure sensitive mechanical switch. Using the multi-layer circular spiral coil
      design, the diameter of the RFID tag is shrunk to 10, 15, 19 and 27 mm to support
      the magnamosis for children as well as adults. With the impedance matching
      network, the operating distance of these four RFID tags are longer than 10 cm in
      a 20 * 22 cm(2) area, even when the tag's normal direction is 45 degrees  off the
      antenna's normal direction. Measurement results also indicate that there is no
      noticeable degradation on the operating distance when the tag is immersed in
      saline or placed next to the rare-earth magnet. The miniaturized RFID tag
      presented in this paper is able to support the magnamosis and other medical
      applications that require the miniaturized RFID tag. 

PMID- 25570041
TI  - A 65nm CMOS low-power MedRadio-band integer-N cascaded phase-locked loop for
      implantable medical systems.
AB  - This paper presents a low-power MedRadio-band integer-N phase-locked Loop (PLL)
      system which is composed of two charge-pump PLLs cascade connected. The PLL
      provides the operation clock and local carrier signals for an implantable medical
      electronic system. In addition, to avoid the off-chip crystal oscillator, the
      13.56 MHz Industrial, Scientific and Medical (ISM) band signal from the wireless
      power transmission system is adopted as the input reference signal for the PLL.
      Ring-based voltage controlled oscillators (VCOs) with current control units are
      adopted to reduce chip area and power dissipation. The proposed cascaded PLL
      system is designed and implemented in TSMC 65-nm CMOS technology. The measured
      jitter for 216.96 MHz signal is 12.23 ps and the phase noise is -65.9 dBc/Hz at
      100 kHz frequency offset under 402.926 MHz carrier frequency. The measured power
      dissipations are 66 MUW in the first PLL and 195 MUW in the whole system under 1
      V supply voltage. The chip area is 0.1088 mm(2) and no off-chip component is
      required which is suitable for the integration of the implantable medical
      electronic system. 

PMID- 25570042
TI  - Physiological constraints for an intraocular inductive distance sensor.
AB  - In this paper the design restrictions of an inductive sensor for an intraocular
      lens with focus control on the basis of a marker implanted in the ciliary muscle
      of the eye are discussed in the framework of anatomical and physiological
      influences and constraints: limitations on the marker size, influences of tissue
      conduction and effects of off-axis implantation of the marker with respect to the
      coil. 

PMID- 25570043
TI  - On the robustness of EMG features for pattern recognition based myoelectric
      control: a multi-dataset comparison.
AB  - The selection of optimal features has long been a subject of debate for pattern
      recognition based myoelectric control. Studies have compared many features, but
      have typically used small or constrained data sets. Herein, the performance of
      various features is evaluated using data from six previously reported data sets.
      The number of channels, the contraction dynamics (dynamic vs static), and
      classifier type all yielded significant interactions (p<;0.05) with the feature
      set. When using 8 channels, the addition of the tested features produced no
      improvement over a standard time domain (TD) feature set alone (p>0.05). When
      using fewer channels, however, autoregressive, Cepstral coefficients, Willison
      amplitude and sample entropy features all provided significant improvement during
      dynamic contractions (p<;0.05). The simple Willison amplitude is highlighted,
      showing that it can provide significant improvement when used as a replacement
      for any one of the standard TD features. 

PMID- 25570044
TI  - Maximizing information transfer rates in an SSVEP-based BCI using individualized
      Bayesian probability measures.
AB  - Successful brain-computer interfaces (BCIs) swiftly and accurately communicate
      the user's intention to a computer. Typically, information transfer rate (ITR) is
      used to measure the performance of a BCI. We propose a multi-step process to
      speed up detection and classification of the user's intent and maximize ITR.
      Users randomly looked at 4 frequency options on the interface in two sessions,
      one without and one with performance feedback. Analysis was performed off-line. A
      ratio of the canonical correlation analysis (CCA) coefficients was used to
      construct a Bayesian probability model and a thresholding method for the ratio of
      the posterior probability of the target frequency over maximal posterior
      probability of non-target frequencies was used as classification criteria.
      Moreover, the probability thresholds were optimized for each frequency, subject
      to maximizing the ITR. We achieved a maximum ITR of 39.82 bit/min. Although the
      performance feedback did not improve the overall ITR, it did improve the accuracy
      measure. Possible applications in the medical industry are discussed. 

PMID- 25570045
TI  - Extending mode switching to multiple degrees of freedom in hand prosthesis
      control is not efficient.
AB  - In recent years, many sophisticated control strategies for multifunctional
      dexterous hand prostheses have been developed. It was indeed assumed that control
      mechanisms based on switching between degrees of freedom, which are in use since
      the 1960's, could not be extended to efficient control of more than two degrees
      of freedom. However, quantitative proof for this assumption has not been shown.
      In this study, we adopted the mode switching paradigm available in commercial
      prostheses for two degree of freedom control and we extended it for the control
      of seven functions (3.5 degrees of freedom) in a modern robotic hand. We compared
      the controllability of this scaled version of the standard method to a state of
      the art pattern recognition based control in an applied online study. The aim was
      to quantify whether multi-functional prosthetic control with mode switching
      outperformed pattern recognition in the control of a real prosthetic hand for
      daily life activities online. Although in simple grasp-release tasks the
      conventional method performed best, tasks requiring more complex control of
      multiple degrees of freedom required a more intuitive control method, such as
      pattern recognition, for achieving high performance. 

PMID- 25570046
TI  - A characterization of the effect of limb position on EMG features to guide the
      development of effective prosthetic control schemes.
AB  - Electromyogram (EMG) pattern recognition has long been used for the control of
      upper limb prostheses. More recently, it has been shown that variability induced
      during functional use, such as changes in limb position and dynamic contractions,
      can have a substantial impact on the robustness of EMG pattern recognition. This
      work further investigates the reasons for pattern recognition performance
      degradation due to the limb position variation. The main focus is on the impact
      of limb position variation on features of the EMG, as measured using separability
      and repeatability metrics. The results show that when the limb is moved to a
      position different from the one in which the classifier is trained, both the
      separability and repeatability of the data decrease. It is shown how two
      previously proposed classification methods, multiple position training and dual
      stage classification, resolve the position effect problem to some extent through
      increasing either separability or repeatability but not both. A hybrid
      classification method which exhibits a compromise between separability and
      repeatability is proposed in this work. It is shown that, when tested with the
      limb in 16 different positions, this method increases classification accuracy
      from an average of 70% (single position training) to 89% (hybrid approach). This
      hybrid method significantly (p<;0.05) outperforms multiple position training (an
      average of 86%) and dual-stage classification (an average of 85%). 

PMID- 25570047
TI  - A reduced rank approach for covariance matrix estimation in EEG signal
      classification.
AB  - Common Spatial Pattern (CSP) methods are widely used to extract the brain
      activity for brain machine interfacing (BMI) based on electroencephalogram (EEG).
      For each mental task, CSP methods estimate a covariance matrix of EEG signals and
      adopt the uniform average of the sample covariance matrices over trials. However,
      the uniform average is sensitive to outliers caused by e.g. unrelated brain
      activity. In this paper, we propose an improvement of the estimated covariance
      matrix utilized in CSP methods by reducing the influence of the outliers as well
      as guaranteeing positive definiteness. More precisely, our estimation is the
      projection of the uniform average onto the intersection of two convex sets: the
      first set is a special reduced dimensional subspace which alleviates the
      influence of the outliers; the second is the positive definite cone. A numerical
      experiment supports the effectiveness of the proposed technique. 

PMID- 25570048
TI  - Selection of effective EEG channels in brain computer interfaces based on
      inconsistencies of classifiers.
AB  - This paper proposed a novel method to select the effective Electroencephalography
      (EEG) channels for the motor imagery tasks based on the inconsistencies from
      multiple classifiers. The inconsistency criterion for channel selection was
      designed based on the fluctuation of the classification accuracies among
      different classifiers when the noisy channels were included. These noisy channels
      were then identified and removed till a required number of channels was selected
      or a predefined classification accuracy with reference to baseline was obtained.
      Experiments conducted on a data set of 13 healthy subjects performing hand
      grasping and idle revealed that the EEG channels from the motor area were most
      frequently selected. Furthermore, the mean increases of 4.07%, 3.10% and 1.77% of
      the averaged accuracies in comparison with the four existing channel selection
      methods were achieved for the non-feedback, feedback and calibration sessions,
      respectively, by selecting as low as seven channels. These results further
      validated the effectiveness of our proposed method. 

PMID- 25570049
TI  - A stochastic modelling framework for the reconstruction of cardiovascular
      signals.
AB  - This paper presents a common stochastic modelling framework for physiological
      signals which allows patient simulation following a synthesis-by-analysis
      approach. Within this framework, we propose a general model-based methodology
      able to reconstruct missing or artifacted signal intervals in cardiovascular
      monitoring applications. The proposed model consists of independent stages which
      provide high flexibility to incorporate signals of different nature in terms of
      shape, cross-correlation and variability. The reconstruction methodology is based
      on model sampling and selection based on a wide range of boundary conditions,
      which include prior information. Results on real data show how the proposed
      methodology fits the particular approaches presented so far for electrocardiogram
      (ECG) reconstruction and how a simple extension within the framework can
      significantly improve their performance. 

PMID- 25570050
TI  - Generalized Linear Models of home activity for automatic detection of mild
      cognitive impairment in older adults.
AB  - With a globally aging population, the burden of care of cognitively impaired
      older adults is becoming increasingly concerning. Instances of Alzheimer's
      disease and other forms of dementia are becoming ever more frequent. Earlier
      detection of cognitive impairment offers significant benefits, but remains
      difficult to do in practice. In this paper, we develop statistical models of the
      behavior of older adults within their homes using sensor data in order to detect
      the early onset of cognitive decline. Specifically, we use inhomogenous Poisson
      processes to model the presence of subjects within different rooms throughout the
      day in the home using unobtrusive sensing technologies. We compare the
      distributions learned from cognitively intact and impaired subjects using
      information theoretic tools and observe statistical differences between the two
      populations which we believe can be used to help detect the onset of cognitive
      decline. 

PMID- 25570051
TI  - Computational study of the influence of callus porosity on ultrasound propagation
      in healing bones.
AB  - In the process of fracture healing, several phases of recovery are observed as
      the mechanical stability, continuity and normal load carrying capacity are
      gradually restored. The ultrasonic monitoring and discrimination of different
      healing stages is a complex process due to the significant microstructure and
      porous nature of osseous and callus tissues. In this study, we investigate the
      influence of the callus pores' size and concentration on ultrasound propagation
      in a long bone at a late healing stage. Different excitation frequencies are
      applied in the range of 300 kHz-1 MHz. A 2D geometry is developed and axial
      transmission calculations are performed based on a Finite Element Method. The
      velocity of the first arriving signal (FAS) and the propagation of guided waves
      are used as the estimated parameters. It was shown that the FAS velocity can
      reflect callus porosity changes, while the propagation of guided waves is
      sensitive to pores' distribution for higher frequencies. 

PMID- 25570052
TI  - Transient brain activity explains the spectral content of steady-state visual
      evoked potentials.
AB  - Steady-state visual evoked potentials (SSVEPs) are widely used in the design of
      brain-computer interfaces (BCIs). A lot of effort has therefore been devoted to
      find a fast and reliable way to detect SSVEPs. We study the link between
      transient and steady-state VEPs and show that it is possible to predict the
      spectral content of a subject's SSVEPs by simulating trains of transient VEPs.
      This could lead to a better understanding of evoked potentials as well as to
      better performances of SSVEP-based BCIs, by providing a tool to improve SSVEP
      detection algorithms. 

PMID- 25570053
TI  - Effects of the series length on Lempel-Ziv Complexity during sleep.
AB  - Lempel-Ziv Complexity (LZC) has been demonstrated to be a powerful complexity
      measure in several biomedical applications. During sleep, it is still not clear
      how many samples are required to ensure robustness of its estimate when computed
      on beat-to-beat interval series (RR). The aims of this study were: i) evaluation
      of the number of necessary samples in different sleep stages for a reliable
      estimation of LZC; ii) evaluation of the LZC when considering inter-subject
      variability; and iii) comparison between LZC and Sample Entropy (SampEn). Both
      synthetic and real data were employed. In particular, synthetic RR signals were
      generated by means of AR models fitted on real data. The minimum number of
      samples required by LZC for having no changes in its average value, for both NREM
      and REM sleep periods, was 10(4) (p<;0.01) when using a binary quantization.
      However, LZC can be computed with N >1000 when a tolerance of 5% is considered
      satisfying. The influence of the inter-subject variability on the LZC was first
      assessed on model generated data confirming what found (>10(4); p<;0.01) for both
      NREM and REM stage. However, on real data, without differentiate between sleep
      stages, the minimum number of samples required was 1.8*10(4). The linear
      correlation between LZC and SampEn was computed on a synthetic dataset. We
      obtained a correlation higher than 0.75 (p<;0.01) when considering sleep stages
      separately, and higher than 0.90 (p<;0.01) when stages were not differentiated.
      Summarizing, we suggest to use LZC with the binary quantization and at least 1000
      samples when a variation smaller than 5% is considered satisfying, or at least
      10(4) for maximal accuracy. The use of more than 2 levels of quantization is not
      recommended. 

PMID- 25570054
TI  - Medically relevant criteria used in EEG compression for improved post-compression
      seizure detection.
AB  - Biomedical signals aid in the diagnosis of different disorders and abnormalities.
      When targeting lossy compression of such signals, the medically relevant
      information that lies within the data should maintain its accuracy and thus its
      reliability. In fact, signal models that are inspired by the biophysical
      properties of the signals at hand allow for a compression that preserves more
      naturally the clinically significant features of these signals. In this paper, we
      illustrate this through the example of EEG signals; more specifically, we analyze
      three specific lossy EEG compression schemes. These schemes are based on signal
      models that have different degrees of reliance on signal production and
      physiological characteristics of EEG. The resilience of these schemes is
      illustrated through the performance of seizure detection post compression. 

PMID- 25570055
TI  - Analysis of magnetoencephalography recordings from Alzheimer's disease patients
      using embedding entropies.
AB  - The aim of this study was to examine the magnetoencephalography (MEG) background
      activity in Alzheimer's disease (AD) using three embedding entropies: approximate
      entropy (ApEn), sample entropy (SampEn), and fuzzy entropy (FuzzyEn). These three
      methods measure the time series regularity. Five minutes of recording were
      acquired with a 148-channel whole-head magnetometer from 36 AD patients and 24
      elderly control subjects. Our results showed that MEG activity was more regular
      in AD patients than in controls. Additionally, FuzzyEn revealed statistically
      significant differences between the two groups (p <; 0.01, Bonferroni-corrected
      Mann-Whitney U-test), while ApEn and SampEn did not. The better discriminating
      results of FuzzyEn in comparison with the other entropy algorithms suggest that
      it is more efficient for the characterization of MEG activity in AD. 

PMID- 25570056
TI  - Stochastic coupled oscillator model of EEG for Alzheimer's disease.
AB  - Coupled nonlinear oscillator models of EEG signals during resting eyes-closed and
      eyes-open conditions are presented based on Duffing-van der Pol oscillator
      dynamics. The frequency and information entropy contents of the output of the
      nonlinear model and the actual EEG signal is matched through an optimization
      algorithm. The framework is used to model and compare EEG signals recorded from
      Alzheimer's disease (AD) patients and age-matched healthy controls (CTL)
      subjects. The results show that 1) the generated model signal can capture the
      frequency and information entropy contents of the EEG signal with very similar
      power spectral distribution and non-periodic time history; 2) the EEG and the
      generated signal from the eyes-closed model are alpha band dominant for CTL
      subjects and theta band dominant for AD patients; and 3) statistically distinct
      models represent the EEG signals from AD patients and CTL subject during resting
      eyes-closed condition. 

PMID- 25570057
TI  - Effect of resistive inspiratory and expiratory loading on cardio-respiratory
      interaction in healthy subjects.
AB  - Resistive loading affects the breathing pattern and causes an increase in
      negative intrathoracic pressure. The aim of this paper was to study the influence
      inspiratory and expiratory loading on cardio-respiratory interaction. We recorded
      electrocardiogram (ECG) and respiratory inductance plethysmogram (RIP) in 11
      healthy male subjects under normal and resistive loading conditions. The R-R time
      series were extracted from the ECG and respiratory phases were calculated from
      the ribcage and abdominal RIP using the Hilbert transform. Both the series were
      transformed into ternary symbol vectors based on the changes between two
      successive R-R intervals or respiratory phases, respectively. Subsequently, words
      of length '3 digits' were formed and the correspondence between words of the two
      series was determined to quantify cardio-respiratory interaction. Adding
      inspiratory and expiratory resistive loads resulted in an increase in inspiratory
      and expiatory time, respectively. Furthermore, we observed a significant increase
      in cardio-respiratory interaction during inspiratory resistive loading as
      compared to expiratory resistive loading (ribcage: 22.1+/-7.2 vs. 12.5+/-4.3 %,
      p<;0.0001; abdomen: 18.8+/-8.5 vs. 12.1+/-3.1 %, p<;0.05, respectively). Further
      studies may aid in better understanding the underlying physiological mechanisms
      and management of patients with breathing disorders. 

PMID- 25570058
TI  - Implementing spiking neuron model and spike-timing-dependent plasticity with
      generalized Laguerre-Volterra models.
AB  - To perform large-scale simulations of the brain or build biologically-inspired
      cognitive architectures, it is essential to have a succinct and flexible model of
      spiking neurons. The model should be able to capture the nonlinear dynamical
      properties of various types of neurons and the nonstationary properties such as
      the spike-timing-dependent plasticity (STDP). In this paper, we propose a
      generalized Laguerre-Volterra modeling approach for such a task. Due to its built
      in nonlinear dynamical terms, the generalized Laguerre-Volterra model (GLVM) can
      capture various biological processes/mechanisms. Using Laguerre expansion of
      Volterra kernel technique, the model is fully represented with a small set of
      coefficients. The calculation of the model variables can be expressed recursively
      based on only the current and the one-step-before values and thus can be
      performed efficiently. In addition, we show that, using the same methodology,
      STDP can be implemented as a specific form of second-order Volterra kernel
      describing the causal relationship between pairs of input-output spikes and the
      changes of the feedforward kernels in the GLVMs. 

PMID- 25570059
TI  - High correlation of double Debye model parameters in skin cancer detection.
AB  - The double Debye model can be used to capture the dielectric response of human
      skin in terahertz regime due to high water content in the tissue. The increased
      water proportion is widely considered as a biomarker of carcinogenesis, which
      gives rise of using this model in skin cancer detection. Therefore, the goal of
      this paper is to provide a specific analysis of the double Debye parameters in
      terms of non-melanoma skin cancer classification. Pearson correlation is applied
      to investigate the sensitivity of these parameters and their combinations to the
      variation in tumor percentage of skin samples. The most sensitive parameters are
      then assessed by using the receiver operating characteristic (ROC) plot to
      confirm their potential of classifying tumor from normal skin. Our positive
      outcomes support further steps to clinical application of terahertz imaging in
      skin cancer delineation. 

PMID- 25570060
TI  - Assessing skin blood flow dynamics in older adults using a modified sample
      entropy approach.
AB  - The aging process may result in attenuated microvascular reactivity in response
      to environmental stimuli, which can be evaluated by analyzing skin blood flow
      (SBF) signals. Among various methods for analyzing physiological signals, sample
      entropy (SE) is commonly used to quantify the degree of regularity of time
      series. However, we found that for temporally correlated data, SE value depends
      on the sampling rate. When data are oversampled, SE may give misleading results.
      To address this problem, we propose to modify the definition of SE by using time
      lagged vectors in the calculation of the conditional probability that any two
      vectors of successive data points are within a tolerance r for m points remain
      within the tolerance at the next point. The lag could be chosen as the first
      minimum of the auto mutual information function. We tested the performance of
      modified SE using simulated signals and SBF data. The results showed that
      modified SE is able to quantify the degree of regularity of the signals
      regardless of sampling rate. Using this approach, we observed a more regular
      behavior of blood flow oscillations (BFO) during local heating-induced maximal
      vasodilation period compared to the baseline in young and older adults and a more
      regular behavior of BFO in older adults compared to young adults. These results
      suggest that modified SE may be useful in the study of SBF dynamics. 

PMID- 25570061
TI  - Detecting volumetric changes in fMRI connectivity networks in schizophrenia
      patients.
AB  - There is a growing interest in identifying neuroimaging-based biomarkers for
      schizophrenia. Previous studies have shown both functional and structural brain
      abnormalities in schizophrenia patients. One main category of these findings
      consists of volumetric abnormalities in brain structure in different cortical and
      subcortical structures in patients' brain. However there has been little work
      investigating changes in the brain's functional volumes. Nor has there been work
      studying differences in brain networks as opposed to single regions. In this
      study, we investigated the volumes of functional networks as potential
      biomarkers. Independent component analysis was used to decompose fMRI images into
      maximally independent spatial maps and corresponding time-courses. Volume of
      functional networks was computed from subject-specific back reconstructed spatial
      maps. The results show that different nodes of the default-mode network exhibit
      volumetric abnormalities in schizophrenia patients. Interestingly these networks
      are larger in patients compared to controls. 

PMID- 25570062
TI  - Using functional MRI alone for localization in focal epilepsy.
AB  - In the present study, we developed a method for the purpose of localizing
      epilepsy related hemodynamic foci for patients suffering intractable focal
      epilepsy using resting state fMRI alone. We studied two groups of subjects: five
      patients with intractable focal epilepsy, and ten healthy volunteers performing
      motor tasks. Spatial independent component analysis (ICA) was performed on the
      fMRI alone data and a set of independent component (IC) selection criteria was
      developed to identify epilepsy related ICs. The method was then evaluated in the
      healthy group with motor tasks. In all five surgery patients, there was at least
      one identified IC concordant with surgical resection. In the motor task study of
      healthy subjects, our method revealed components with concordant spatial and
      temporal features as expected from the unilateral motor tasks. These results
      suggest the lateralization and localization value of fMRI alone in presurgical
      evaluation for patients with intractable unilateral focal epilepsy. The proposed
      method is noninvasive in nature and easy to implement. It has the potential to be
      incorporated in current presurgical workup for the diagnosis of intractable focal
      epilepsy patients. 

PMID- 25570063
TI  - SOM and MCODE methods of defining functional clusters in MRI of the brain.
AB  - Recent advances in analysis of fMRI have established the existence of functional
      sub-networks in the human brain that are active during the performance of visual,
      motor, language, and other tasks. We describe two computational methods of
      delineating functional sub-networks that are active when an individual performs
      an approach-avoidance paradigm. The paradigm consisted of presentation of images
      of pleasant and unpleasant faces that were shown to nine volunteers for 10
      seconds after a preceding rest period of 50 seconds during which a green computer
      screen was displayed. The subjects were instructed to squeeze a ball with their
      right hand if they judged the face to be unpleasant, in which case the unpleasant
      face would disappear. An fMRI BOLD activation was created and used as input for
      two different kinds of clustering method: The MCODE algorithm based on graph
      theoretical analysis and a Conscious Self-Organizing Map (CSOM). Clustering
      obtained with both methods was based on the temporal variations of the fMRI BOLD
      signal activity. Both methods identified distinct regions in the brain which were
      separated by long-range connections. The MCODE algorithm was supplied with time
      courses for activated voxels when performing the paradigm, while the CSOM
      clustering used all voxels in the brain. Both yielded similar clusters for
      activated voxels. The combination of MCODE and CSOM presents a new approach in
      identifying functional subunits in the human brain and warrants further
      investigation into the subject. 

PMID- 25570064
TI  - A DTI study to probe tumor microstructure and its connection with hypoxia.
AB  - Solid tumors have chaotic organization of blood vessels, disruptive nerve paths
      and muscle fibers that result in a hostile and heterogeneous microenvironment.
      These tumor regions are often hypoxic and resistant to radiation therapy. The
      knowledge of partial pressure of oxygen concentration (pO2), in conjunction with
      the information about tissue organization, can predict tissue health and may
      eventually be used in combination with intensity-modulated radiation therapy
      (IMRT) for targeted destruction of radiation-resistant areas, while sparing
      healthy tissues. Diffusion tensor imaging (DTI) based parameter fractional
      anisotropy (FA) can be used to assess organization of tissue microstructure,
      whereas the pO2 can be measured using electron paramagnetic resonance oxygen
      imaging (EPROI). This study is our first step to connect these two important
      physiological parameters. We calculated FA in fixed fibrosarcoma (FSa) grown in
      hind leg of nude mice (n = 6) using preclinical 9.4 T MRI. The FA in tumor region
      (0.34 +/- 0.014) was found to be lower when compared to normal surrounding region
      (0.36 +/- 0.013). We hypothesized that the change in FA is directly correlated
      with the change in oxygen concentration in tumor. We present preliminary in vivo
      results showing a positive correlation (R = 0.85, p = 0.017) between the FA and
      pO2 values acquired for MCa4 tumor (n = 1) using DTI and EPROI. 

PMID- 25570065
TI  - Assessment of white matter microstructure in stroke patients using NODDI.
AB  - Diffusion weighted imaging (DWI) is widely used to study changes in white matter
      following stroke. In various studies employing diffusion tensor imaging (DTI) and
      high angular resolution diffusion imaging (HARDI) modalities, it has been shown
      that fractional anisotropy (FA), mean diffusivity (MD), and generalized FA (GFA)
      can be used as measures of white matter tract integrity in stroke patients.
      However, these measures may be non-specific, as they do not directly delineate
      changes in tissue microstructure. Multi-compartment models overcome this
      limitation by modeling DWI data using a set of indices that are directly related
      to white matter microstructure. One of these models which is gaining popularity,
      is neurite orientation dispersion and density imaging (NODDI). This model uses
      conventional single or multi-shell HARDI data to describe fiber orientation
      dispersion as well as densities of different tissue types in the imaging voxel.
      In this paper, we apply for the first time the NODDI model to 4-shell HARDI
      stroke data. By computing NODDI indices over the entire brain in two stroke
      patients, and comparing tissue regions in ipsilesional and contralesional
      hemispheres, we demonstrate that NODDI modeling provides specific information on
      tissue microstructural changes. We also introduce an information theoretic
      analysis framework to investigate the non-local effects of stroke in the white
      matter. Our initial results suggest that the NODDI indices might be more specific
      markers of white matter reorganization following stroke than other measures
      previously used in studies of stroke recovery. 

PMID- 25570067
TI  - Automated face extraction and normalization of 3D Mesh Data.
AB  - 3D stereophotography is rapidly being adopted by medical researchers for analysis
      of facial forms and features. An essential step for many applications using 3D
      face data is to first crop the head and face from the raw images. The goal of
      this paper is to develop a reliable automatic methodology for extracting the face
      from raw data with texture acquired from a stereo imaging system, based on the
      medical researchers' specific requirements. We present an automated process,
      including eye and nose estimation, face detection, Procrustes analysis and final
      noise removal to crop out the faces and normalize them. The proposed method shows
      very reliable results on several datasets, including a normal adult dataset and a
      very challenging dataset consisting of infants with cleft lip and palate. 

PMID- 25570066
TI  - Diffusion tensor MRI phantom exhibits anomalous diffusion.
AB  - This paper reports diffusion weighted MRI measurements of cyclohexane in a novel
      diffusion tensor MRI phantom composed of hollow coaxial electrospun fibers
      (average diameter 10.2 MUm). Recent studies of the phantom demonstrated its
      potential as a calibration standard at low b values (less than 1000
      s/mm<;sup>2<;/sup>) for mean diffusivity and fractional anisotropy. In this
      paper, we extend the characterization of cyclohexane diffusion in this
      heterogeneous, anisotropic material to high b values (up to 5000
      s/mm<;sup>2<;/sup>), where the apparent diffusive motion of the cyclohexane
      exhibits anomalous behavior (i.e., the molecular mean squared displacement
      increases with time raised to the fractional power 2alpha/beta). Diffusion tensor
      MRI was performed at 9.4 T using an Agilent imaging scanner and the data fit to a
      fractional order Mittag-Leffler (generalized exponential) decay model. Diffusion
      along the fibers was found to be Gaussian (2alpha/beta=l), while diffusion across
      the fibers was sub-diffusive (2alpha/beta<;l). Fiber tract reconstruction of the
      data was consistent with scanning electron micrograph images of the material.
      These studies suggest that this phantom material may be used to calibrate MR
      systems in both the normal (Gaussian) and anomalous diffusion regimes. 

PMID- 25570068
TI  - Ensemble learning for the detection of facial dysmorphology.
AB  - Down syndrome is the most common chromosomal condition that presents
      characteristic facial morphology and texture patterns. The early detection of
      Down syndrome through an automatic, non-invasive and simple way is desirable and
      critical to provide the best health management to newborns. In this study, we
      propose such a computer-aided diagnosis system for Down syndrome from photography
      based on facial analysis with ensemble learning. First, geometric and texture
      facial features are extracted based on automatically located facial landmarks,
      followed by feature fusion and selection. Then multiple classifiers (i.e. support
      vector machines, random forests and linear discriminant analysis) are adopted to
      identify patients with Down syndrome. An accurate and reliable decision is
      finally achieved by optimally combining the outputs of these individual
      classifiers via ensemble learning that captures both the shared and complementary
      information from different classifiers. The best performance was achieved by
      using the median ensemble rule with 0.967 accuracy, 0.977 precision and 0.933
      recall. 

PMID- 25570069
TI  - Quantification of skull deformity for craniofacial research.
AB  - Craniosynostosis, a disorder in which one or more fibrous joints of the skull
      fuse prematurely, causes skull malformation and may be associated with increased
      intracranial pressure and developmental delays. In order to perform medical
      research studies that relate phenotypic abnormalities to outcomes such as
      cognitive ability or results of surgery, biomedical researchers need an automated
      methodology for quantifying the degree of abnormality of the disorder. This paper
      addresses that need by proposing a set of features derived from CT scans of the
      skull that can be used for this purpose. A thorough set of experiments is used to
      evaluate the features as compared to two human craniofacial experts in a ranking
      evaluation. 

PMID- 25570070
TI  - Using the Kinect to detect potentially harmful hand postures in pianists.
AB  - Pianists who practice hours per day may have a risk for developing playing
      related musculoskeletal injuries if they do not play with proper hand alignment.
      In order to detect the harmful, misaligned hand postures (such as wrist flexion
      and extension, knuckle collapse, and ulnar and radial deviation) and analyze the
      injury risk, a motion capture system was developed using the Microsoft Kinect
      depth camera. Data were captured on professional pianists and student pianists
      from the School of Music, University of Missouri. Features extracted from the 3D
      point clouds reconstructed from the Kinect depth images are used for hand posture
      evaluation. Results are included for different hand postures of participating
      pianists. 

PMID- 25570071
TI  - Bodypart localization for pressure ulcer prevention.
AB  - Pressure ulcers, commonly called bedsores, are defined as injuries to the skin
      and underlying tissue resulting from prolonged pressure usually on bony areas of
      the body, such as heels and hips. In order to alleviate pressure accumulation at
      high-risk regions, the current practice in clinics requires caregivers to
      reposition their patients every two hours. This relies on the engagement of
      nursing services and places large burdens on the caregivers. In this study, a
      bedsore monitoring method using Pictorial Structure models is introduced to
      localize pressure distributions of the body. A pilot study including 12 subjects
      reveals that the proposed method enables reliable localization of bodyparts with
      89.8% accuracy in common lying postures. 

PMID- 25570072
TI  - Detecting human falls with 3-axis accelerometer and depth sensor.
AB  - Previous work demonstrated that Kinect sensor can be very useful for fall
      detection. In this work we present a novel approach to fall detection that allows
      us to achieve reliable fall detection in larger areas through person detection
      and tracking in dense depth map sequences acquired by an active pan-tilt 3D
      camera. We demonstrate that both high sensitivity and specificity can be obtained
      using dense depth images acquired by a ceiling mounted Kinect and executing the
      proposed algorithms for lying pose detection and motion analysis. The person is
      extracted using depth region growing and person detection. 

PMID- 25570073
TI  - Microfluidic devices for rapid and sensitive identification of organisms.
AB  - Microfluidic devices for rapid and highly sensitive detection of living organisms
      were developed for two applications. First, a zebrafish embryo genotyping system
      was developed and shown to be able to genotype embryos in the first 48 hours of
      the embryos life without damaging the embryos in any apparent way. Second, a
      highly sensitive bacteria detection platform has been developed for the rapid
      detection of pathogens. The system relies on a magnetic bead extraction followed
      by secondary bead attachment. The secondary beads are barcoded with DNA sequences
      highly enriched for Gs. The guanine molecules generate an electrochemical
      response after they are released from the secondary beads and detected at a
      sensing location downstream from the beads. The amplification with the efficient
      washing procedures leads to a limit of detection of 3 CFU in 100 mL of water. 

PMID- 25570074
TI  - A journey of trains of droplets in droplet-based microfluidic devices.
AB  - In this paper, we propose a microfluidic platform toseparate magnetic particles
      with a constant volumetric flow condition. In order to realize this architecture,
      three main functions for a droplet manipulation based system are integrated into
      a single device: synchronization of droplets by matching a location of droplets;
      lateral electro-coalescence; and magnetic particle manipulation. For an optimized
      condition of this device, a droplet generation was controlled by varying a
      droplet size at a fixed flow rate ratio 0.86. The electro-coalescence efficiency
      and maximum throughput are investigated at a given flow rate condition. 

PMID- 25570075
TI  - Complex micropatterning of proteins within microfluidic channels.
AB  - Microfluidic channels containing protein micropatterned surfaces are useful in
      many bioanalytical and biological applications. In this study, we developed a new
      method to integrate microfluidics and protein micropatterning by attaching
      poly(dimethylsiloxane) (PDMS) microfluidic channels to bio-friendly photoresist
      films via poly(dopamine) (PDA) adhesive. A bio-friendly photoresist poly(2,2
      dimethoxy nitrobenzyl methacrylate-r-methyl methacrylate-r-poly(ethylene glycol)
      methacrylate) (PDMP) was synthesized and used. By performing microscope
      projection photolithography (MPP) to the PDMP thin films within PDMS
      microchannels, complex micropatterns of proteins were successfully generated
      within microfluidic channels. 

PMID- 25570076
TI  - MECs: building blocks for custom microfluidic diagnostics in the developing
      world.
AB  - Microfluidic diagnostics for use in the developing world face a number of unique
      challenges. Doctors and nurses in developing countries are best suited to
      addresses these challenges, but they lack the resources and training needed to
      develop their own microfluidic diagnostics. To address this need, we are
      developing a system of Multifluidic Evolutionary Components or MECs, "building
      blocks" that can be snapped together by healthcare providers in resource-limited
      settings to build custom diagnostic instruments. MECs operate on multiple scales
      of fluid volumes (from nanoliters to milliliters) and include not only fluidic
      but also optical, mechanical, and electronic functions. In this work we share
      several prototype MECs and use them to build a demonstration instrument capable
      of measuring the pH of a sample. 

PMID- 25570077
TI  - Clinical overview of the need for technologies for around-the-clock monitoring of
      the health status of severely disabled autistic children.
AB  - Despite the growing incidence and costs of autism, little has been done to apply
      technology advancements to the challenges faced by autistic individuals. The
      recent introduction of digital data collection to track the progress of treatment
      interventions has been an important contribution, but there are many other
      opportunities for technology to facilitate the development of autistic children
      and to assist the clinical staff who work with them. The realization of wearable
      devices to identify and track behaviors would significantly reduce the manual
      input of data into digital devices, and wireless physiological monitoring has the
      potential to provide predictors of unwanted behaviors. The development of such
      tools would change the intervention paradigms that currently exist. 

PMID- 25570078
TI  - Combining psychological and engineering approaches to utilizing social robots
      with children with autism.
AB  - It is estimated that Autism Spectrum Disorder (ASD) affects 1 in 68 children.
      Early identification of an ASD is exceedingly important to the introduction of an
      intervention. We are developing a robot-assisted approach that will serve as an
      improved diagnostic and early intervention tool for children with autism. The
      robot, named PABI(r) (Penguin for Autism Behavioral Interventions), is a compact
      humanoid robot taking on an expressive cartoon-like embodiment. The robot is
      affordable, durable, and portable so that it can be used in various settings
      including schools, clinics, and the home. Thus enabling significantly enhanced
      and more readily available diagnosis and continuation of care. Through facial
      expressions, body motion, verbal cues, stereo vision-based tracking, and a tablet
      computer, the robot is capable of interacting meaningfully with an autistic
      child. Initial implementations of the robot, as part of a comprehensive treatment
      model (CTM), include Applied Behavioral Analysis (ABA) therapy where the child
      interacts with a tablet computer wirelessly interfaced with the robot. At the
      same time, the robot makes meaningful expressions and utterances and uses stereo
      cameras in eyes to track the child, maintain eye contact, and collect data such
      as affect and gaze direction for charting of progress. In this paper we present
      the clinical justification, anticipated usage with corresponding requirements,
      prototype development of the robotic system, and demonstration of a sample
      application for robot-assisted ABA therapy. 

PMID- 25570079
TI  - A paraeducator glove for counting disabled-child behaviors that incorporates a
      Bluetooth Low Energy wireless link to a smart phone.
AB  - Behavior tracking with severely disabled children can be a challenge, since
      dealing directly with a child's behavior is more immediately pressing than the
      need to record an event for tracking purposes. By the time a paraeducator
      ('para') is able to break away and record events, behavior counts can be
      forgotten. This paper presents a paraeducator glove design that can help to track
      behaviors with minimal distraction by allowing a paraeducator to touch their
      thumb to one of their other four fingers, where each finger represents a
      different behavior. Count data are packaged by a microcontroller board on the
      glove and then sent wirelessly to a smart phone via a Bluetooth Low Energy (BLE)
      link. A customized BLE profile was designed for this application to promote real
      time recording. These data can be forwarded to a database for further analysis.
      This para glove design addresses basic needs of a wearable device that employs
      BLE, including local data collection, BLE data transmission, and remote data
      recording. More functional sensors can be added to this platform to support other
      wearable scenarios. 

PMID- 25570080
TI  - Sensors and instrumentation for unobtrusive sleep quality assessment in autistic
      children.
AB  - Little is understood about the sleep quality of children with autism and other
      developmental disabilities. Conventional sensors and instrumentation for
      objective sleep quality assessment, such as those used in polysomnography, are
      highly obtrusive and not well-suited to this patient population. This paper
      presents a set of sensors and instrumentation for unobtrusive measurement of
      physiological and behavioral parameters indicative of sleep quality.
      Specifically, load cells, an electromechanical film, and thermocouples are used
      to measure respiratory rate, pulse rate, and physical activity of a subject lying
      on a bed. The sensor suite is being developed to monitor sleep quality of
      children at Heartspring, a residential and educational facility in Wichita, KS
      that serves children with severe developmental disabilities. These technologies
      have the potential to provide objective sleep quality assessment for children in
      their home environment. 

PMID- 25570081
TI  - A hybrid dynamic Bayesian network approach for modelling temporal associations of
      gene expressions for hypertension diagnosis.
AB  - Computational and machine learning techniques have been applied in identifying
      biomarkers and constructing predictive models for diagnosis of hypertension.
      Strategies such as improved classification rules based on decision trees have
      been proposed. Other techniques such as Fuzzy Expert Systems (FES) and Neuro
      Fuzzy Systems (NFS) have recently been applied. However, these methods lack the
      ability to detect temporal relationships among biomarker genes that will aid
      better understanding of the mechanism of hypertension disease. In this paper we
      apply a proposed two-stage bio-network construction approach that combines the
      power and computational efficiency of classification methods with the well
      established predictive ability of Dynamic Bayesian Network. We demonstrate our
      method using the analysis of male young-onset hypertension microarray dataset.
      Four key genes were identified by the Least Angle Shrinkage and Selection
      Operator (LASSO) and three Support Vector Machine Recursive Feature Elimination
      (SVM-RFE) methods. Results show that cell regulation FOXQ1 may inhibit the
      expression of focusyltransferase-6 (FUT6) and that ABCG1 ATP-binding cassette sub
      family G may also play inhibitory role against NR2E3 nuclear receptor sub-family
      2 and CGB2 Chromatin Gonadotrophin. 

PMID- 25570082
TI  - Prediction of protein allergenicity based on signal-processing bioinformatics
      approach.
AB  - Current bioinformatics tools accomplish high accuracies in classifying allergenic
      protein sequences with high homology and generally perform poorly with low
      homology protein sequences. Although some homologous regions explained
      Immunoglobulin E (IgE) cross-reactivity in groups of allergens, no universal
      molecular structure could be associated with allergenicity. In addition, studies
      have showed that cross-reactivity is not directly linked to the homology between
      protein sequences. Therefore, a new homology independent method needs to be
      developed to determine if a protein is an allergen or not. The aim of this study
      is therefore to differentiate sets of allergenic and non-allergenic proteins
      using a signal-processing based bioinformatics approach. In this paper, a new
      method was proposed for characterisation and classification of allergenic protein
      sequences. For this method hydrophobicity amino acid index was used to encode
      proteins to numerical sequences and Discrete Fourier Transform to extract
      features for each protein. Finally, a classifier was constructed based on Support
      Vector Machines. In order to demonstrate the applicability of the proposed method
      857 allergen and 1000 non-allergen proteins were collected from UniProt online
      database. The results obtained from the proposed method yielded: MCC: 0.752 +/-
      0.007, Specificity: 0.912 +/- 0.005, Sensitivity: 0.835 +/- 0.008 and Total
      Accuracy: 87.65% +/- 0.004.

PMID- 25570083
TI  - Hybrid imbalanced data classifier models for computational discovery of
      antibiotic drug targets.
AB  - Identification of drug candidates is an important but also difficult process.
      Given drug resistance bacteria that we face, this process has become more
      important to identify protein candidates that demonstrate antibacterial activity.
      The aim of this study is therefore to develop a bioinformatics approach that is
      more capable of identifying a small but effective set of proteins that are
      expected to show antibacterial activity, subsequently to be used as antibiotic
      drug targets. As this is regarded as an imbalanced data classification problem
      due to smaller number of antibiotic drugs available, a hybrid classification
      model was developed and applied to the identification of antibiotic drugs. The
      model was developed by taking into account of various statistical models leading
      to the development of six different hybrid models. The best model has reached the
      accuracy of as high as 50% compared to earlier study with the accuracy of less
      than 1% as far as the proportion of the candidates identified and actual
      antibiotics in the candidate list is concerned.

PMID- 25570084
TI  - Construction of protein dendrograms based on amino acid indices and Discrete
      Fourier Transform.
AB  - From the literature, existing methods use pairwise percent identity to identify
      the percentage of similarity between two protein sequences, in order to create a
      dendrogram. As this is a parametric method of measuring the similarities between
      proteins, and different parameter may yield different results, this method does
      not guarantee that the global optimal similarity values will be found. As protein
      dendrogram construction is used in other areas, such as multiple protein sequence
      alignments, it is very important that the most related protein sequences to be
      identified and align first. Furthermore, by using the pairwise percent identity
      of the protein sequences to construct the dendrograms, the physical
      characteristics of protein sequences and amino acids are not considered. In this
      paper, a new method was proposed for constructing protein sequence dendrograms.
      For this method, Discrete Fourier Transform, was used to construct the distance
      matrix in combination with the multiple amino acid indices that were used to
      encode protein sequences into numerical sequences. In order to show the
      applicability and robustness of the proposed method, a case study was presented
      by using nine Cluster of Differentiation 4 protein sequences extracted from the
      UniProt online database.

PMID- 25570085
TI  - Symmetrical directional dual-tree complex wavelet packet transform.
AB  - In this study, a symmetrical directional complex discrete wavelet packet
      transform, which can be applied directly to the quadrature format signals and has
      the ability of mapping directional information during decomposition stage, is
      proposed. With the proposed symmetrical directional complex wavelet packet
      transform, traditional symmetrical phasing filter technique, which is used for
      quadrature signal to directional signal conversion, is eliminated and the
      computational complexity of whole process is reduced. The performance of proposed
      method is examined in detail using real quadrature embolic signals. 

PMID- 25570086
TI  - Uncertainty quantification of the optimal stimulation area in an electro
      stimulative hip revision system.
AB  - Electro-stimulative hip revision systems accelerate the bone growth around the
      implant and are capable of reducing the number of side effects such as aseptic
      implant loosening. A computational model was developed to determine the optimal
      electrode arrangement for such a system, which is currently under development.
      The optimization process depends on the electrical properties of bone material
      and the used bone substitute, which are subject to uncertainty in literature and
      its production process, respectively. To quantify the influence of these
      uncertain parameters on the optimal stimulation ratio (OSR), the computationally
      effective non-intrusive polynomial chaos technique was applied. The results
      indicate that the conductivity of bone substitute is most sensitive to the OSR,
      while its uncertainty was comparatively small compared to that of the uncertain
      parameters.

PMID- 25570087
TI  - Modeling muscle's nonlinear viscoelastic dynamics.
AB  - Muscle's contractile properties are complicated by its viscoelastic properties.
      Failure of early viscoelastic muscle models led to Hill's force-velocity relation
      embodied as the contractile element. Adopting a particular force-velocity
      relation to describe muscle is neither easy, nor unique [1]. Time-varying
      elastance based models of the left ventricle have been popular since the idea was
      presented in 1969 [2]. This paper investigates adoption of the time-varying
      elastance concept to describe the viscoelastic properties of muscle. It will be
      shown that a time-varying elastance must be extended to a time, length, and
      velocity dependent elastance. Results show how a generalized force generator
      description of muscle [3] may be used to realistically model muscle's
      viscoelasticity.

PMID- 25570088
TI  - Supine to upright lung mechanics: do changes in lung shape influence lung tissue
      deformation?
AB  - In this study we analyze lung shape change between the upright and supine
      postures and the effect of this shape change on the deformation of lung tissue
      under gravity. We use supine computed tomography images along with upright
      tomosynthesis images obtained on the same day to show that there is significant
      diaphragmatic movement between postures. Using a continuum model of lung tissue
      deformation under gravity we show that the shape changes due to this
      diaphragmatic movement could result in different lung tissue expansion patterns
      between supine and upright lungs. This is an essential consideration when
      interpreting imaging data acquired in different postures or translating data
      acquired in supine imaging to upright function.

PMID- 25570089
TI  - Simulation of a computational winding filament model with an exponential spring
      to represent titin.
AB  - The goal of developing high fidelity simulation of muscle force is of
      considerable interest for the biomedical community. Traditionally Hill models
      have been incorporated. However, feasible scope of the Hill model is inherently
      limited, especially in light of the growing relevance of muscle history
      dependence. History dependence is considered to be significant for motor control
      and stability. Attempts have been made to augment the Hill model to emulate
      history dependence. The titin winding filament model best elucidates history
      dependence of muscle force including force enhancement. The recent version of the
      titin winding filament model accounts for the functionality of titin through a
      pulley linked with the contractile element and a linear spring to represent the
      elastic properties of titin. A new and more realistic amendment to the winding
      filament model is incorporation of an exponential spring to characterize the
      elastic properties of titin. A sensitivity study as a function of the titin
      exponential spring constant is presented. Overall the amalgamation of the titin
      exponential spring to the winding filament model improves the respective force
      enhancement characteristics with a relatively more optimal exponential spring
      constant that provides a maximal averaged coefficient of determination.

PMID- 25570090
TI  - Coupling effect on thermal comfort in a typical cubicle-based office with
      personalized floor diffuser control.
AB  - A typical office layout with cubicles, in which occupants have their own control
      of the micro-environment by adjusting supply air flow rate of the floor diffuser,
      is numerically investigated for the impact of the discrepancy in personal thermal
      sensation preference on thermal comfort. The comparison among different scenarios
      indicates that whether the local thermal comfort is significantly affected by the
      neighboring cubicle (coupling effect) depends on whether the doorway is closed or
      not whereas the "openness", of upper space has no influence on such coupling
      effect but observably on the thermal comfort. The effect of thermoregulation is
      also presented and compared with conventional constant heat flux assumption for
      the occupants. 

PMID- 25570091
TI  - A finite element model of flatfoot (Pes Planus) for improving surgical plan.
AB  - Flatfoot is a foot condition caused by the collapse of the medial arch of the
      foot, and it can result in problems such as severe pain, swelling, abnormal gait,
      and difficulty walking. Despite being a very common foot deformity, flatfoot is
      one of the least understood orthopaedic problems, and the opinions regarding its
      optimal treatment vary widely. In this paper, an FE model of a flatfoot is
      proposed that is based on CT measurements. Surface meshes of the bones and soft
      tissue were generated from CT images and then simplified to reduce the node
      density. A total of 62 ligaments, 9 tendons, and the plantar fascia were modeled
      manually. Volume meshes of the different components were generated and combined
      to form the completed flatfoot model. A dynamic FE formulation was derived, and a
      balanced standing simulation was performed. The model was validated by comparing
      stress distribution results from the simulation to experimental data.

PMID- 25570092
TI  - Elastic mesh braided worm robot for locomotive endoscopy.
AB  - This paper presents a new design of worm robot whose body is constructed using a
      novel crimped elastic mesh braid inspired by the earthworm. The proposed worm
      robot is intended for inspection within the human body via natural orifices. The
      design and fabrication procedure of the worm robot are given in the paper. The
      imitation of peristalsis, used by natural worms, is used to control the worm
      robot for the purpose of producing motion while causing minimal trauma to
      biological tissue. The forward locomotive function of the worm robot has been
      tested on both a flat surface and in a rubber tube. It is shown that the worm
      robot is capable of propagating forwards for both test conditions in a form
      similar to the earthworm. The test results indicate the proposed worm robot
      design has promising application for natural tube inspection, like the colon and
      the esophagus. 

PMID- 25570093
TI  - Needle geometry, target migration and substrate interactions in high resolution.
AB  - Recent investigations considering flexible, steer-able needles for minimally
      invasive surgery have shown the significance of needle shape in determining the
      needle-tissue interactions leading to the access of targets. Digital Image
      Correlation has enabled internal deformation and strain caused by needle
      insertions to be seen in a soft tissue phantom at high resolution for the first
      time. Here, the impact of tip design on strains and displacements of material
      around the insertion axis is presented using Digital Image Correlation in a
      stable, plane-strain configuration. Insight into the shape of needles to minimise
      tissue trauma and generate interactions that would enable optimal steering
      conditions is provided. Needle tips with an included bevel angle up to 40 degrees
      result in asymmetric displacement of the surrounding tissue phantom. Increasing
      the included tip angle to 60 degrees  results in more predictable displacement
      and strains that may enhance steering forces with little negative impact on the
      phantom.

PMID- 25570094
TI  - Rate dependency during needle insertions with a biologically inspired steering
      system: an experimental study.
AB  - Percutaneous intervention is a common Minimally Invasive (MI) surgical procedure
      for the treatment of various disorders. It generally involves the insertion of
      slender needles deep within tissue, as lesions can be several centimetres below
      skin level. Consequently, deviations might occur which need to be accounted for
      and corrected by steering the needle tip during the insertion process. Needle
      steering systems, however, are necessarily disruptive to the substrate, with the
      potential to cause larger migrations of deep-seated targets, as well as
      potentially increasing the extent of tissue trauma at the needle interface, when
      compared to straight needles. This study aims to investigate different insertion
      modalities for a biologically inspired multi-segment needle, which is able to
      steer along three-dimensional trajectories by exploiting a quasi-linear
      relationship between the relative displacement of the needle segments and the
      curvature magnitude and direction plane at the tip. We demonstrate that different
      segment insertion speeds do not affect this relationship during experiments in
      gelatine, and thus a new steering approach is proposed to steer the needle into
      the substrate which substantially improves upon the manoeuvrability (i.e. the
      rate of change of steering angle) of the needle.

PMID- 25570095
TI  - RICA: a reliable and image configurable arena for cyborg bumblebee based on CAN
      bus.
AB  - In this paper, we designed a reliable and image configurable flight arena, RICA,
      for developing cyborg bumblebees. To meet the spatial and temporal requirements
      of bumblebees, the Controller Area Network (CAN) bus is adopted to interconnect
      the LED display modules to ensure the reliability and real-time performance of
      the arena system. Easily-configurable interfaces on a desktop computer
      implemented by python scripts are provided to transmit the visual patterns to the
      LED distributor online and configure RICA dynamically. The new arena system will
      be a power tool to investigate the quantitative relationship between the visual
      inputs and induced flight behaviors and also will be helpful to the visual-motor
      research in other related fields.

PMID- 25570096
TI  - Pressure distribution-based texture sensing by using a simple artificial
      mastication system.
AB  - This paper proposes a novel texture sensing method for nursing-care gel by using
      an artificial mastication system, in which not only mechanical characteristics
      but also geometrical ones are objectively and quantitatively evaluated. When
      human masticates gel food, she or he perceives the changes of the shape and
      contact force simultaneously. Based on the impressions, they evaluate the
      texture. For reproducing such a procedure, the pressure distribution of gel is
      measured in the simple artificial mastication, and the information associated to
      both the geometrical and mechanical characteristics is simultaneously acquired.
      The relationship between the value of sensory evaluation (i.e. impression human
      perceives), and the pressure distribution data is numerically modeled by applying
      the image texture analysis. Experimental results show that the proposed method
      succeeds in estimating the values of sensory evaluation of nine kinds of gel with
      the coefficient of determination greater than 0.93.

PMID- 25570097
TI  - Theoretical analysis of magnetically propelled microrobots in the cardiovascular
      system.
AB  - The field of medical microrobotics is rapidly progressing; however, it is
      particularly challenging to control microrobots inside blood vessels. In this
      paper, the magnetic propulsion of a microrobot in pulsating flow is investigated.
      Regarding this task, the advantages of a reduced blood flow velocity are
      examined. The required magnetic field gradient in relation to the size of the
      microrobot is theoretically analyzed and compared to that for propulsion during
      reduced blood flow velocity. Quantitative and qualitative advantages together
      with the practical challenges are discussed. 

PMID- 25570098
TI  - Design and clinical feasibility of personal wearable monitor for measurement of
      activity and environmental exposure.
AB  - Human exposure to specific environmental factors (e.g. air quality, lighting, and
      sound) is known to play an important role in the pathogenesis of many chronic
      diseases (e.g. asthma) and mental health disorders (e.g. anxiety). However,
      conventional fixed environmental monitoring stations are sparsely located and,
      despite environmental models, cannot adequately assess individual exposure
      levels. New forms of low-cost portable monitors have begun to emerge that enable
      the collection of higher spatial density "crowd sourced" data; however, the first
      generation of these low-cost environmental monitors have generally not been
      suitable for clinical environmental health studies due to practical challenges
      such as calibration, reproducibility, form factor, and battery life. In this
      paper, we present a wearable environmental monitor that overcomes these
      challenges and can be used in clinical studies The new device, called "Eco-Mini,"
      can be used without a smart phone and is capable of locally sampling and
      recording a variety of environmental parameters (Ozone, Sulfur Dioxide, Volatile
      Organic Compounds, humidity, temperature, ambient light color balance, and sound
      level) as well as individual activity (3-axis accelerometer) and location (GPS).
      In this paper, we also report findings and discuss lessons learned from a
      feasibility study conducted for one week with pediatric patients as part of an
      ongoing asthma research study.

PMID- 25570100
TI  - On-demand wireless infusion rate control in an implantable micropump for patient
      tailored treatment of chronic conditions.
AB  - Wireless infusion rate control and programmability for an implantable, low power,
      electrochemical micropump is presented. Flow rate control was achieved through
      adjustment of the wiper position of a current potentiometer in the wireless
      receiver (0.6-3.2 mA output current with a resolution of 0.2 mA per step). An off
      the-shelf Bluetooth module and Basic Stamp microcontroller kit was used to
      initiate amplitude-shift keying (ASK) modulation of the inductive power signal.
      Accurate flow control of two model regimens was achieved on benchtop. Wireless
      transmission (power transfer and control) was not affected by simulated tissue
      material placed between the transmitter and receiver.

PMID- 25570099
TI  - A wireless implantable switched-capacitor based optogenetic stimulating system.
AB  - This paper presents a power-efficient implantable optogenetic interface using a
      wireless switched-capacitor based stimulating (SCS) system. The SCS efficiently
      charges storage capacitors directly from an inductive link and periodically
      discharges them into an array of micro-LEDs, providing high instantaneous power
      without affecting wireless link and system supply voltage. A custom-designed
      computer interface in LabVIEW environment wirelessly controls stimulation
      parameters through the inductive link, and an optrode array enables simultaneous
      neural recording along with optical stimulation. The 4-channel SCS system
      prototype has been implemented in a 0.35-MUm CMOS process and combined with the
      optrode array. In vivo experiments involving light-induced local field potentials
      verified the efficacy of the SCS system. An implantable version of the SCS system
      with flexible hermetic sealing is under development for chronic experiments.

PMID- 25570101
TI  - Real-time implementation of cochlear implant speech processing pipeline on
      smartphones.
AB  - This paper presents the real-time implementation of an adaptive speech processing
      pipeline for cochlear implants on the smartphone platform. The pipeline is
      capable of real-time classification of background noise environment and automated
      tuning of a noise suppression component based upon the detected background noise
      environment. This pipeline was previously implemented on the FDA-approved PDA
      platform for cochlear implant studies. The paper discusses the steps taken to
      achieve the real-time implementation of the pipeline on the smartphone platform.
      In addition, it includes the real-time timing as well as the noise suppression
      results when the entire pipeline was run on the smartphone platform. 

PMID- 25570102
TI  - Currents induced by fast movements inside the MRI room may cause inhibition in an
      implanted pacemaker.
AB  - The static magnetic field generated by MRI systems is highly non-homogenous and
      rapidly decreases when moving away from the bore of the scanner. Consequently,
      the movement around the MRI scanner is equivalent to an exposure to a time
      varying magnetic field at very low frequency (few Hz). If people with an
      implanted pacemaker (PM) enter the MRI room, fast movements may thus induce
      voltages on the loop formed by the PM lead, with the potential to modify the
      correct behavior of the stimulator. In this study, we performed in-vitro
      measurements on a human-shaped phantom, equipped with an implantable PM and with
      a current sensor, able to monitor the activity of the PM while moving the phantom
      in the MRI room. Fast rotational movements in close proximity of the bore of the
      scanner caused the inappropriate inhibition of the PM, programmed in VVI
      modality, maximum sensitivity, unipolar sensing and pacing. The inhibition
      occurred for a variation of the magnetic field of about 3 T/s. These findings
      demonstrate that great care must be paid when extending PM MRI compatibility from
      patients to healthcare personnel, since the safety procedures and the MRI
      conditional PM programming (e.g. asynchronous stimulation or bipolar sensing)
      used for patients cannot be applied.

PMID- 25570103
TI  - Feasibility of pulse presence and pulse strength assessment during head-up tilt
      table testing using an accelerometer located at the carotid artery.
AB  - Neurally mediated syncope (NMS) is a disorder of the autonomic regulation of
      postural tone, which is characterized by hypotension and/or bradycardia,
      resulting in cerebral hypo-perfusion and finally in a sudden loss of
      consciousness. Prediction of an impending NMS requires detection of pulse
      presence to derive heart rate (HR) as well as to assess the pulse strength (PS)
      related to systolic blood pressure (SBP) preferably from a single body location
      only. This paper analyses the basic feasibility of using a single accelerometer
      positioned above the common carotid artery to assess pulse strength and pulse
      rate towards NMS prediction. A physical model has been investigated to gain
      insights into expected signal morphologies and potential feature candidates vs.
      hemodynamic parameters such as SBP, pulse pressure (PP) and PR relevant for NMS
      detection. Model results are compared with first measurements obtained in a head
      up tilt table test (HUTT) from a patient during impending syncope. We show that
      an accelerometer positioned at the carotid artery is a potential approach
      offering a valuable tool in syncope management.

PMID- 25570104
TI  - Autonomous mobile platform for enhanced situational awareness in Mass Casualty
      Incidents.
AB  - To enhance the efficiency of the search and rescue process of a Mass Casualty
      Incident, we introduce a low cost autonomous mobile platform. The mobile platform
      motion is controlled by an Android Smartphone mounted on a robot. The pictures
      and video captured by the Smartphone camera can significantly enhance the
      situational awareness of the incident commander leading to a more efficient
      search and rescue process. Moreover, the active RFID readers mounted on the
      mobile platform can improve the localization accuracy of victims in the disaster
      site in areas where the paramedics are not present, reducing the triage and
      evacuation time.

PMID- 25570105
TI  - Automatic generation of indoor navigation instructions for blind users using a
      user-centric graph.
AB  - The complexity and diversity of indoor environments brings significant challenges
      to automatic generation of navigation instructions for blind and visually
      impaired users. Unlike generation of navigation instructions for robots, we need
      to take into account the blind users wayfinding ability. In this paper we
      introduce a user-centric graph based solution for cane users that takes into
      account the blind users cognitive ability as well as the user's mobility
      patterns. We introduce the principles of generating the graph and the algorithm
      used to automatically generate the navigation instructions using this graph. We
      successfully tested the efficiency of the instruction generation algorithm, the
      correctness of the generated paths, and the quality of the navigation
      instructions. Blindfolded sighted users were successful in navigating through a
      three-story building. 

PMID- 25570106
TI  - Smartphone-based evaluation of parkinsonian hand tremor: quantitative
      measurements vs clinical assessment scores.
AB  - With an ever-growing number of technologically advanced methods for the diagnosis
      and quantification of movement disorders, comes the need to assess their accuracy
      and see how they match up with widely used standard clinical assessment tools.
      This work compares quantitative measurements of hand tremor in twenty-three
      Parkinson's disease patients, with their clinical scores in the hand tremor
      components of the Unified Parkinson's Disease Rating Scale (UPDRS), which is
      considered the "gold standard" in the clinical assessment of the disease. Our
      measurements were obtained using a smartphone-based platform, which processes the
      phone's accelerometer and gyroscope signals to detect and measure hand tremor.
      The signal metrics used were mainly based on the magnitude of the acceleration
      and the rotation rate vectors of the device. Our results suggest relatively
      strong correlation (r>0.7 and p<;0.01) between the patients' UPDRS hand tremor
      scores and the signal metrics applied to the measured signals.

PMID- 25570107
TI  - A WBAN based cableless ECG acquisition system.
AB  - A Wireless Body Area Network (WBAN) based 3-lead cableless electrocardiography
      (ECG) acquisition system is described. To enable truly cableless ECG monitoring,
      a new ECG measurement configuration and method that acquires ECG signals at
      individual lead locations referenced to a localized ground is proposed. The
      synthesized ECG signals are evaluated against the standard wired 3-lead
      configuration on the same test subject. Average Pearson correlation coefficients
      of 0.82, 0.95 and 0.86 have been achieved for Lead I, II and III signals
      respectively, demonstrating a high degree of similarity in the synthesized
      signals. Measurements are obtained via a custom wireless network platform
      utilizing a TDMA-based MAC protocol supporting the star topology and a
      proprietary front-end ECG acquisition system. 

PMID- 25570109
TI  - Energy-efficient adaptive modulation in wireless communication for implanted
      medical devices.
AB  - In contrast to conventional wireless communication which takes place over the
      air, Radio Frequency (RF) communication through the human body poses unique
      challenges. Studies on RF propagation through human body indicate that the
      heterogeneous body tissues with different dielectric properties constitute a
      complicated and lossy environment for signal propagation. This environment also
      varies with different implant positions, individuals, body shapes and postures.
      As a result, there is a large variation in the path loss value of the in-body
      communication channel. In this paper, we first examine the energy efficiency of
      different digital modulation schemes in a basic wireless implant system. We point
      out that using a fixed type of modulation does not help to achieve the best
      energy efficiency in the implant system that has varying channel conditions. We
      then propose an adaptive communication system model which is suitable for
      wireless medical implant. Simulations results show that adopting adaptive
      modulation can provide a considerable amount of energy saving.

PMID- 25570108
TI  - Measuring in-home walking speed using wall-mounted RF transceiver arrays.
AB  - In this paper we present a new method for passively measuring walking speed using
      a small array of radio transceivers positioned on the walls of a hallway within a
      home. As a person walks between a radio transmitter and a receiver, the received
      signal strength (RSS) detected by the receiver changes in a repeatable pattern
      that may be used to estimate walking speed without the need for the person to
      wear any monitoring device. The transceivers are arranged as an array of 4 with a
      known distance between the array elements. Walking past the first pair of
      transceivers will cause a peak followed by a second peak when the person passes
      the second pair of transceivers. The time difference between these peaks is used
      to estimate walking speed directly. We further show that it is possible to
      estimate the walking speed by correlating the shape of the signal using a single
      pair of transceivers positioned across from each other in a hallway or doorframe.
      RMSE performance was less than 15 cm/s using a 2-element array, and less than 8
      cm/s using a 4-element array relative to a gait mat used for ground truth.

PMID- 25570110
TI  - Automatic detection and classification of artifacts in single-channel EEG.
AB  - Ambulatory EEG monitoring can provide medical doctors important diagnostic
      information, without hospitalizing the patient. These recordings are however more
      exposed to noise and artifacts compared to clinically recorded EEG. An automatic
      artifact detection and classification algorithm for single-channel EEG is
      proposed to help identifying these artifacts. Features are extracted from the EEG
      signal and wavelet subbands. Subsequently a selection algorithm is applied in
      order to identify the best discriminating features. A non-linear support vector
      machine is used to discriminate among different artifact classes using the
      selected features. Single-channel (Fp1-F7) EEG recordings are obtained from
      experiments with 12 healthy subjects performing artifact inducing movements. The
      dataset was used to construct and validate the model. Both subject-specific and
      generic implementation, are investigated. The detection algorithm yield an
      average sensitivity and specificity above 95% for both the subject-specific and
      generic models. The classification algorithm show a mean accuracy of 78 and 64%
      for the subject-specific and generic model, respectively. The classification
      model was additionally validated on a reference dataset with similar results.

PMID- 25570111
TI  - Artefact detection in neonatal EEG.
AB  - Artefact detection is an important component of any automated EEG analysis. It is
      of particular importance in analyses such as sleep state detection and EEG
      grading where there is no null state. We propose a general artefact detection
      system (GADS) based on the analysis of the neonatal EEG. This system aims to
      detect both major and minor artefacts (a distinction based primarily on
      amplitude). As a result, a two-stage system was constructed based on 14 features
      extracted from EEG epochs at multiple time scales: [2, 4, 16, 32]s. These
      features were combined in a support vector machine (SVM) in order to determine
      the presence of absence of artefact. The performance of the GADS was estimated
      using a leave-one-out cross-validation applied to a database of hour long
      recordings from 51 neonates. The median AUC was 1.00 (IQR: 0.95-1.00) for the
      detection of major artefacts and 0.89 (IQR: 0.83-0.95) for the detection of minor
      artefacts.

PMID- 25570112
TI  - Comparison of sleep-wake classification using electroencephalogram and wrist-worn
      multi-modal sensor data.
AB  - This paper presents the comparison of sleep-wake classification using
      electroencephalogram (EEG) and multi-modal data from a wrist wearable sensor. We
      collected physiological data while participants were in bed: EEG, skin
      conductance (SC), skin temperature (ST), and acceleration (ACC) data, from 15
      college students, computed the features and compared the intra-/inter-subject
      classification results. As results, EEG features showed 83% while features from a
      wrist wearable sensor showed 74% and the combination of ACC and ST played more
      important roles in sleep/wake classification. 

PMID- 25570113
TI  - Distance-informed metric learning for Alzheimer's disease staging.
AB  - Identifying intermediate biomarkers of Alzheimer's disease (AD) is of great
      importance for diagnosis and prognosis of the disease. In this study, we develop
      a new AD staging method to classify patients into Normal Controls (NC), Mild
      Cognitive Impairment (MCI), and AD groups. Our solution employs a novel metric
      learning technique that improves classification rates through the guidance of
      some weak supervisory information in AD progression. More specifically, those
      information are in the form of pairwise constraints that specify the relative
      Mini Mental State Examination (MMSE) score disparity of two subjects, depending
      on whether they are in the same group or not. With the imposed constraints, the
      common knowledge that MCI generally sits in between of NC and AD can be
      integrated into the classification distance metric. Subjects from the Alzheimer's
      Disease Neuroimaging Initiative cohort (ADNI; 56 AD, 104 MCI, 161 controls) were
      used to demonstrate the improvements made comparing with two state-of-the-art
      metric learning solutions: large margin nearest neighbors (LMNN) and relevant
      component analysis (RCA).

PMID- 25570114
TI  - Using type-2 fuzzy logic systems for spike detection in the hypoxic ischemic EEG
      of the preterm fetal sheep.
AB  - Perinatal hypoxia is a major cause of brain injury in preterm babies. Thus, neuro
      protective treatments play a pivotal role during the first 6-8 hours post hypoxic
      ischemic insult. However, at present it is not possible to determine which
      infants are suffering from hypoxic ischemia. Recent investigations suggest that
      there are high frequency micro-scale transients exist in the first 6-8 hours of a
      hypoxic ischemic EEG which could be utilized as the useful benchmarks for the
      prediction of hypoxia. Type-2 Fuzzy Logic Systems (Type-2 FLS) have the
      capability to handle inherent uncertainties in nonlinear signals. This paper
      describes the application of a Type-2 FLS to detect spikes in the preterm fetal
      sheep electroencephalogram (EEG) after asphyxia in utero. The Type-2 FLS
      differentiates each detected event in terms of its spikiness and specifies the
      potential events based on their degree of similarity to an EEG expert definition
      of a standard spike. An adaptive thresholding method has been employed in order
      to increase the spike detection ability of the purposed system. The sensitivity
      and selectivity verify enhanced performance of the Type-2 FLS for spike detection
      in fetal sheep EEG signals with a 98.1% and 93.7% respectively which are
      significantly improved in comparison to our previous methods.

PMID- 25570115
TI  - Detection of tonic epileptic seizures based on surface electromyography.
AB  - The purpose of this project was to design an algorithm for detection of tonic
      seizures based on surface electromyography signals from the deltoids. A
      successful algorithm has a future prospect of being implemented in a wearable
      device as part of an alarm system. This has already been done for generalized
      tonic-clonic seizures, and the hypothesis was that some of the same
      characteristics could be found for tonic seizures. The signals were pre-processed
      by a high-pass filter to remove low frequency noise such as movement artifacts.
      Several different features were investigated, including kurtosis, median
      frequency, zero crossing rate and approximate entropy. These features were used
      as input in the random forest classifier to decide if a data segment was from a
      seizure or not. The goal was to develop a generic algorithm for all tonic
      seizures, but better results were achieved when certain parameters were adapted
      specifically for each patient. With patient specific parameters the algorithm
      obtained a sensitivity of 100% for four of six patients with false detection
      rates between 0.08 and 7.90 per hour.

PMID- 25570116
TI  - Brain dynamics based automated epileptic seizure detection.
AB  - We developed and tested a seizure detection algorithm based on two measures of
      nonlinear and linear dynamics, that is, the adaptive short-term maximum Lyapunov
      exponent (ASTLmax) and the adaptive Teager energy (ATE). The algorithm was tested
      on long-term (0.5-11.7 days) continuous EEG recordings from five patients (3 with
      intracranial and 2 with scalp EEG) with a total of 56 seizures, producing a mean
      sensitivity of 91% and mean specificity of 0.14 false positives per hour. The
      developed seizure detection algorithm is data-adaptive, training-free, and
      patient-independent.

PMID- 25570117
TI  - Sparse representation of MER signals for localizing the Subthalamic Nucleus in
      Parkinson's disease surgery.
AB  - Deep brain stimulation (DBS) of Subthalamic Nucleus (STN) is the best method for
      treating advanced Parkinson's disease (PD), leading to striking improvements in
      motor function and quality of life of PD patients. During DBS, online analysis of
      microelectrode recording (MER) signals is a powerful tool to locate the STN.
      Therapeutic outcomes depend of a precise positioning of a stimulator device in
      the target area. In this paper, we show how a sparse representation of MER
      signals allows to extract discriminant features, improving the accuracy in
      identification of STN. We apply three techniques for over-complete representation
      of signals: Method of Frames (MOF), Best Orthogonal Basis (BOB) and Basis Pursuit
      (BP). All the techniques are compared to classical methods for signal processing
      like Wavelet Transform (WT), and a more sophisticated method known as adaptive
      Wavelet with lifting schemes (AW-LS). We apply each processing method in two real
      databases and we evaluate its performance with simple supervised classifiers.
      Classification outcomes for MOF, BOB and BP clearly outperform WT and AW-LF in
      all classifiers for both databases, reaching accuracy values over 98%.

PMID- 25570118
TI  - "Super e-noses": Multi-layer perceptron classification of volatile odorants from
      the firing rates of cross-species olfactory receptor arrays.
AB  - Current electronic noses, or e-noses, that employ insect odorant receptors (Ors)
      as their sensory front end are potentially limited by the fact that the Ors come
      from a single species. In addition, a realistic e-nose also demands low numbers
      of Ors at its sensory front end due to the difficulties of receptor/sensor
      integration and functionalisation. In this work, we report the first
      investigations of a 'Super E-Nose' that incorporates Ors from both the model
      organism Drosophila melanogaster fruit fly (DmOr) and the mosquito, Anopheles
      gambiae (AgOr). Furthermore, we report how an Artificial Neural Network (ANN), in
      the form of a hybrid double hidden layer Multi-Layer Perceptron (MLP), can be
      used to determine the optimal Ors that provide the best prediction performance in
      the classification of unknown odorants into their respective chemical class. Our
      findings demonstrate how 3-Or arrays consisting of DmOr only, AgOr only, or cross
      species DmOr-AgOr combinations correctly classified all unknown odorants of the
      validation set. In addition, we report that all 3-Or combinations perform equally
      well as the complete 74 DmOr-AgOr array. Thus, the results of this work support
      further investigation into cross-species 'Super E-noses' coupled with hybrid MLPs
      for the classification of unknown odorants.

PMID- 25570119
TI  - A smartphone approach for the 2 and 6-minute walk test.
AB  - The 2 and 6-minute walk tests (2-6MWT) are used by rehabilitation professionals
      as a measure of exercise capacity. Our research has produced a new 2-6MWT
      BlackBerry smartphone application (app) that can be used to run the 2-6MWT and
      also provide new information about how the person moves during the test. The
      smartphone is worn on a belt at the lower back to record phone sensor data while
      walking. This data is used to identify foot strikes, calculate the total distance
      walked and step timing, and analyze pelvis accelerations. Information on
      symmetry, walking changes over time, and poor walking patterns is not available
      from a typical 2-6MWT and could help with clinical decision-making. The 2-6MWT
      app was evaluated in a pilot test using data from five able-bodied participants.
      Foot strike time was within 0.07 seconds when compared to gold standard video
      recordings. The total distance calculated by the app was within 1m of the
      measured distance. 

PMID- 25570121
TI  - Application of head flexion detection for enhancing eye gaze direction
      classification.
AB  - Extensive research has been conducted on the tracking and detection of the eye
      gaze and head movement detection as these aspects of technology can be applied as
      alternative approaches for various interfacing devices. This paper proposes
      enhancements to the classification of the eye gaze direction. Viola Jones face
      detector is applied to first declare the region of the eye. Circular Hough
      Transform is then used to detect the iris location. Support Vector Machine (SVM)
      is applied to classify the eye gaze direction. Accuracy of the system is enhanced
      by calculating the flexion angle of the head through the utilization of a
      microcontroller and flex sensors. In case of rotated face images, the face can be
      rotated back to zero degrees through the flexion angle calculation. This is while
      Viola Jones face detector is limited to face images with very little or no
      rotation angle. Accuracy is initiated by enhancing the effectiveness of the
      system in the overall procedure of classifying the direction of the eye gaze.
      Therefore, the head direction is a main determinant in enhancing the control
      method. Different control signals are enhanced by the eye gaze direction
      classification and the head direction detection.

PMID- 25570120
TI  - Calibration-free gaze tracking for automatic measurement of visual acuity in
      human infants.
AB  - Most existing vision-based methods for gaze tracking need a tedious calibration
      process. In this process, subjects are required to fixate on a specific point or
      several specific points in space. However, it is hard to cooperate, especially
      for children and human infants. In this paper, a new calibration-free gaze
      tracking system and method is presented for automatic measurement of visual
      acuity in human infants. As far as I know, it is the first time to apply the
      vision-based gaze tracking in the measurement of visual acuity. Firstly, a
      polynomial of pupil center-cornea reflections (PCCR) vector is presented to be
      used as the gaze feature. Then, Gaussian mixture models (GMM) is employed for
      gaze behavior classification, which is trained offline using labeled data from
      subjects with healthy eyes. Experimental results on several subjects show that
      the proposed method is accurate, robust and sufficient for the application of
      measurement of visual acuity in human infants.

PMID- 25570122
TI  - Multiple-output support vector machine regression with feature selection for
      arousal/valence space emotion assessment.
AB  - Human emotion recognition (HER) allows the assessment of an affective state of a
      subject. Until recently, such emotional states were described in terms of
      discrete emotions, like happiness or contempt. In order to cover a high range of
      emotions, researchers in the field have introduced different dimensional spaces
      for emotion description that allow the characterization of affective states in
      terms of several variables or dimensions that measure distinct aspects of the
      emotion. One of the most common of such dimensional spaces is the bidimensional
      Arousal/Valence space. To the best of our knowledge, all HER systems so far have
      modelled independently, the dimensions in these dimensional spaces. In this
      paper, we study the effect of modelling the output dimensions simultaneously and
      show experimentally the advantages in modeling them in this way. We consider a
      multimodal approach by including features from the Electroencephalogram and a few
      physiological signals. For modelling the multiple outputs, we employ a multiple
      output regressor based on support vector machines. We also include an stage of
      feature selection that is developed within an embedded approach known as
      Recursive Feature Elimination (RFE), proposed initially for SVM. The results show
      that several features can be eliminated using the multiple output support vector
      regressor with RFE without affecting the performance of the regressor. From the
      analysis of the features selected in smaller subsets via RFE, it can be observed
      that the signals that are more informative into the arousal and valence space
      discrimination are the EEG, Electrooculogram/Electromiogram (EOG/EMG) and the
      Galvanic Skin Response (GSR).

PMID- 25570123
TI  - EEG-based emotion recognition with manifold regularized extreme learning machine.
AB  - EEG signals, which can record the electrical activity along the scalp, provide
      researchers a reliable channel for investigating human emotional states. In this
      paper, a new algorithm, manifold regularized extreme learning machine (MRELM), is
      proposed for recognizing human emotional states (positive, neutral and negative)
      from EEG data, which were previously evoked by watching different types of movie
      clips. The MRELM can simultaneously consider the geometrical structure and
      discriminative information in EEG data. Using differential entropy features
      across whole five frequency bands, the average accuracy of MRELM is 81.01%, which
      is better than those obtained by GELM (80.25%) and SVM (76.62%). The accuracies
      obtained from high frequency band features (beta, gamma) are obviously superior
      to those of low frequency band features, which shows beta and gamma bands are
      more relevant to emotional states transition. Moreover, experiments are conducted
      to further evaluate the efficacy of MRELM, where the training and test sets are
      from different sessions. The results demonstrate that the proposed MRELM is a
      competitive model for EEG-based emotion recognition.

PMID- 25570124
TI  - A comparative analysis of functional connectivity data in resting and task
      related conditions of the brain for disease signature of OCD.
AB  - Obsessive Compulsive Disorder (OCD) is a frequent, chronic disorder producing
      intrusive thoughts which results in repetitive behaviors. It is thought that this
      psychological disorder occurs due to abnormal functional connectivity in certain
      regions of the brain called Default Mode Network (DMN) mainly. Recently,
      functional MRI (FMRI) studies were performed in order to compare the differences
      in brain activity between patients with OCD and healthy individuals through
      different conditions of the brain. Our previous study on extraction of disease
      signature for OCD that is determining the features for discrimination of OCD
      patients from healthy individuals based on their resting-sate functional
      connectivity (rs-FC) data had given encouraging results. In the present study,
      functional data extracted from FMRI images of subjects under imagination task
      (maintaining an image in mind, im-FC) is considered. The aim of this study is to
      compare classification results achieved from both resting and task-related
      (imagination) conditions. This research has shown quite interesting and promising
      results using the same classification (SVM) method.

PMID- 25570126
TI  - Whole brain EEG synchronization likelihood modulated by long term evolution
      electromagnetic fields exposure.
AB  - In this paper, we aimed to investigate the possible interactions between human
      brain and radiofrequency electromagnetic fields (EMF) with electroencephalogram
      (EEG) technique. Unlike the previous studies which mainly focused on EMF effect
      on local brain activities, we attempted to evaluate whether the EMF emitted from
      Long Term Evolution (LTE) devices can modulate the functional connectivity of
      brain electrical activities. Ten subjects were recruited to participate in a
      crossover, double-blind exposure experiment which included two sessions (real and
      sham exposure). In each session, LTE EMF exposure (power on or off) lasted for 30
      min and the EEG signals were collected with 32 channels throughout the
      experiment. Then we applied the synchronization likelihood method to quantify the
      neural synchronization over the whole brain in different frequency bands and in
      different EEG record periods. Our results illustrated that the short-term LTE EMF
      exposure would modulate the synchronization patterns of EEG activation across the
      whole brain. 

PMID- 25570125
TI  - Cluster-based analysis for characterizing dynamic functional connectivity.
AB  - Different regions in the resting brain exhibit non-stationary functional
      connectivity (FC) over time. In this paper, a simple and efficient framework of
      clustering the variability in FC of a rat's brain at rest is proposed. This
      clustering process reveals areas that are always connected with a chosen region,
      called seed voxel, along with the areas exhibiting variability in the FC. This
      addresses an issue common to most dynamic FC analysis techniques, which is the
      assumption that the spatial extent of a given network remains constant over time.
      We increase the voxel size and reduce the spatial resolution to analyze variable
      FC of the whole resting brain. We hypothesize that the adjacent voxels in resting
      state functional magnetic resonance imaging (rsfMRI), just as in task-based fMRI,
      exhibit similar intensities, so they can be averaged to obtain larger voxels
      without any significant loss of information. Sliding window correlation is used
      to compute variable patterns of the rat's whole brain FC with the seed voxel in
      the sensorimotor cortex. These patterns are grouped based on their spatial
      similarities using binary transformed feature vectors in k-means clustering, not
      only revealing the variable and nonvariable portions of FC in the resting brain
      but also detecting the extent of the variability of these patterns.

PMID- 25570127
TI  - Differences in hemispherical thalamo-cortical causality analysis during resting
      state fMRI.
AB  - Thalamus is a very important part of the human brain. It has been reported to act
      as a relay for the messaging taking place between the cortical and sub-cortical
      regions of the brain. In the present study, we analyze the functional network
      between both hemispheres of the brain with the focus on thalamus. We used
      conditional Granger causality (CGC) and time-resolved partial directed coherence
      (tPDC) to investigate the functional connectivity. Results of CGC analysis
      revealed the asymmetry between connection strengths of the bilateral thalamus.
      Upon testing the functional connectivity of the default-mode network (DMN) at low
      frequency fluctuations (LFF) and comparing coherence vectors using Spearman's
      rank correlation, we found that thalamus is a better source for the signals
      directed towards the contralateral regions of the brain, however, when thalamus
      acts as sink, it is a better sink for signals generated from ipsilateral regions
      of the brain.

PMID- 25570128
TI  - A multi sensing method for robust measurement of physiological parameters in
      wearable devices.
AB  - The monitoring of physiological parameters such as heart rate, ventilatory rate,
      or oxygen saturation is a commonly used practice in the medical field. Many
      clinical solutions exist, based on the use of specific sensors, dedicated for
      bedside patient's vital functions monitoring at hospital. But the implementation
      of such sensors in ambulatory situations is rendered extremely difficult because
      of many artifacts induced by the movements of the subject that make the measures
      unusable. We have designed an original method for robust measurement of
      physiological parameters dedicated for wearable devices. The method is based on a
      multi sensing technique using, at least, two sensors of different nature or
      placed at different sites, for each parameter. In order to illustrate this
      method, we have developed a headset device including two heart rate (HR) sensors
      and two ventilatory rate (VR) sensors. This device has been evaluated on 6
      healthy volunteers during exercises. This test showed the physiological values of
      HR and VR from the headset device stability and efficiency.

PMID- 25570129
TI  - Quantitative assessment of synchronization during atrial fibrillation based on a
      novel index.
AB  - Atrial Fibrillation (AF), a chaotic rhythm classically considered with random
      electrical activity, is now demonstrated to show a certain degree of organization
      and synchronization. Rather than those traditional indices which always focus on
      the pairwise properties of adjacent signals, a new synchronization index-S
      estimator-is introduced in this paper to quantify the synchronization level for
      all the signals in a selected area. By evaluating a complement of the entropy of
      the normalized eigenvalues of the corresponding correlation matrix, S estimator
      is designed to be proportional to the amount of synchronization. 400 episodes of
      64-channel epicardial signals acquired from four living mongrels were studied
      under normal sinus rhythm (SN) and AF. The results showed that there were
      significant decreases of S estimator for both anterior left atrium and anterior
      right atrium with the rhythm changing from SN to AF. After dividing the research
      area into eight subparts, S estimator is also capable to demonstrate the
      different synchronization level for each subpart and revealed the
      electrophysiology individual difference among four experimental subjects. In
      conclusion, S estimator succeeds in estimating the synchronization degree for
      multi-channel signals in a selected area, with no limits to the number of the
      signals to be analyzed. It can help us to distinguish the region with a high
      synchronization level during AF, which would be helpful to the clinical AF
      treatment and enhance our understanding of underlying mechanisms of AF.

PMID- 25570130
TI  - EEG-based brain connectivity analysis of states of unawareness.
AB  - This work investigates phase synchrony as a neuro-marker for the identification
      of two brain states: coma and quasi-brain-death. Scalp electroencephalography
      (EEG) data of 34 patients were recorded in an intensive care unit (ICU), with 17
      recordings for patients in a coma state, and 17 recordings for patients in a
      quasi-brain-death state. Phase synchrony was used for feature extraction from EEG
      recording by comparing the phase value between pairs of electrodes using an
      entropy based measure. In particular, we performed phase synchrony analysis in
      five standard frequency bands and provide visualization of the phase synchronies
      in matrices. The effectiveness of the phase synchrony features in each of the
      frequency bands are evaluated with statistical analysis. Results suggest phase
      synchrony for coma patients has a significant increase in the theta / alpha band
      compared to quasi-brain-death patients. Hence, we propose phase synchrony as a
      candidate for the identification of consciousness states between coma and quasi
      brain-death. 

PMID- 25570131
TI  - An adaptive phase-locking insight to unravel mRNAs synchrony from microarray
      experiments.
AB  - A bulk mRNA expression time course can slow or advance modulating in phase the
      averaged expression of each gene within the cell-cycle. This is also a
      synchronism induced at the cycle start to recognize periodic genes. Consistent
      with the above, a novel adaptive phase-locking insight into microarray experiment
      is provided. The budding-yeast expression of the major role in the cell-division
      cycle could be clustered in phase by a new amplitude noise immune approach which
      compares well to meta-analysis of the web Cyclebase and to previous results in
      the field. The new approach to timing elucidation seems to be well matched to
      cellular phenomena and might be promising as the most accurate ever applied in
      Fourier context. 

PMID- 25570132
TI  - Linear and non-linear interdependence of EEG and HRV frequency bands in human
      sleep.
AB  - The characterisation of functional interdependencies of the autonomic nervous
      system (ANS) stands an evergrowing interest to unveil electroencephalographic
      (EEG) and Heart Rate Variability (HRV) interactions. This paper presents a
      biosignal processing approach as a supportive computational resource in the
      estimation of sleep dynamics. The application of linear, non-linear methods and
      statistical tests upon 10 overnight polysomnographic (PSG) recordings, allowed
      the computation of wavelet coherence and phase locking values, in order to
      identify discerning features amongst the clinical healthy subjects. Our findings
      showed that neuronal oscillations theta, alpha and sigma interact with cardiac
      power bands at mid-to-high rank of coherence and phase locking, particularly
      during NREM sleep stages.

PMID- 25570133
TI  - Detection of change points in phase data: a Bayesian analysis of habituation
      processes.
AB  - Given a time series of data points, as obtained in biosignal monitoring, the
      change point problem poses the question of identifying times of sudden variations
      in the parameters of the underlying data distribution. We propose a method for
      extracting a discrete set of change points from directional data. Our method is
      based on a combination of the Bayesian change point model (CPM) and the Viterbi
      algorithm. We apply our method to the instantaneous phase information of single
      trial auditory event-related potentials (ERPs) in a long term habituation
      paradigm. We have seen in previous studies that the phase information enters a
      phase-locked mode with respect to the repetition of a stimulus in the state of
      focused attention. With adaptation to an insignificant stimulus, attention tends
      to trail away (long-term habituation), characterized by changes in the phase
      signature, becoming more diffuse across trials. We demonstrate that the proposed
      method is suitable for detecting the effects of long-term habituation on phase
      information in our experimental setting.

PMID- 25570134
TI  - Does machine-mediated interaction induce inter-brain synchrony?--A hyperscanning
      study.
AB  - We present a study in which participants were trained in several sessions to
      control a (comparatively simple) robot via an EEG-/motor imagery-based Brain
      Computer Interface (BCI). In the final (experiment) session pairs of participants
      were formed and each participant controlled one of two robots in a shared space.
      EEG data was recorded synchronously from both participants. We performed a joint
      data analysis on the datasets and found increases of phase-locking in MU- and
      theta-band. One such phase-locking effect appears to be time-locked to the start
      of the robotic action.

PMID- 25570135
TI  - Homology and topology based metrics for evaluating cortical parcellations
      generated using diffusion MRI.
AB  - When using diffusion MRI for segmenting the cerebral cortex, the modality of
      information used and workflow procedural factors can have significant effects on
      the resulting parcellation. There is as yet no consensus on best practice
      processing protocols, and no ground truth is available in vivo. Converging
      indirect evidence has been used to compare parcellation outcomes, including: (1)
      comparison of cortical parcellations based on different modalities; (2)
      reproducibility across independent acquisitions; (3) consistency across modality
      or subject; and (4) the extent to which the segmented regions are functionally
      distinct based on task or rsfMRI data. To these we add an additional strategy
      wherein parcellation results are assessed based on known organizational
      principles of the brain, specifically inter-hemispheric homology and topology,
      thereby permitting assessment of results per subject independently of another
      imaging modality or acquisition. We propose these measures to guide improvements
      in acquisition, reconstruction, and/or clustering approaches during the process
      of diffusion MRI parcellation.

PMID- 25570136
TI  - Brain functional networks extraction based on fMRI artifact removal: Single
      subject and group approaches.
AB  - Independent component analysis (ICA) has been widely applied to identify brain
      functional networks from multiple-subject fMRI. However, the best approach to
      handle artifacts is not yet clear. In this work, we study and compare two ICA
      approaches for artifact removal using simulations and real fMRI data. The first
      approach, recommended by the human connectome project, performs ICA on individual
      data to remove artifacts, and then applies group ICA on the cleaned data from all
      subjects. We refer to this approach as Individual ICA artifact Removal Plus Group
      ICA (TRPG). A second approach, Group Information Guided ICA (GIG-ICA), performs
      ICA on group data, and then removes the artifact group independent components
      (ICs), followed by individual subject ICA using the remaining group ICs as
      spatial references. Experiments demonstrate that GIG-ICA is more accurate in
      estimation of sources and time courses, more robust to data quality and quantity,
      and more reliable for identifying networks than IRPG.

PMID- 25570137
TI  - Manifold learning based registration algorithms applied to multimodal images.
AB  - Manifold learning algorithms are proposed to be used in image processing based on
      their ability in preserving data structures while reducing the dimension and the
      exposure of data structure in lower dimension. Multi-modal images have the same
      structure and can be registered together as monomodal images if only structural
      information is shown. As a result, manifold learning is able to transform multi
      modal images to mono-modal ones and subsequently do the registration using mono
      modal methods. Based on this application, in this paper novel similarity measures
      are proposed for multi-modal images in which Laplacian eigenmaps are employed as
      manifold learning algorithm and are tested against rigid registration of PET/MR
      images. Results show the feasibility of using manifold learning as a way of
      calculating the similarity between multimodal images.

PMID- 25570139
TI  - Canonical cerebellar graph wavelets and their application to FMRI activation
      mapping.
AB  - Wavelet-based statistical parametric mapping (WSPM) is an extension of the
      classical approach in fMRI activation mapping that combines wavelet processing
      with voxel-wise statistical testing. We recently showed how WSPM, using graph
      wavelets tailored to the full gray-matter (GM) structure of each individual's
      brain, can improve brain activity detection compared to using the classical
      wavelets that are only suited for the Euclidian grid. However, in order to
      perform analysis on a subject-invariant graph, canonical graph wavelets should be
      designed in normalized brain space. We here introduce an approach to define a
      fixed template graph of the cerebellum, an essential component of the brain,
      using the SUIT cerebellar template. We construct a corresponding set of canonical
      cerebellar graph wavelets, and adopt them in the analysis of both synthetic and
      real data. Compared to classical SPM, WSPM using cerebellar graph wavelets shows
      superior type-I error control, an empirical higher sensitivity on real data, as
      well as the potential to capture subtle patterns of cerebellar activity.

PMID- 25570138
TI  - Integration of sparse Bayesian learning and random subspace for fMRI Multivariate
      Pattern Analysis.
AB  - Multivariate Pattern Analysis (MVPA) is frequently used to decode cognitive
      states from brain activities in fMRI study. Due to the discrepancy between sample
      and feature size, MVPA methods are suffered from the overfitting problem. This
      paper addresses this issue by introducing sparse modelling along with its
      advanced decoding method, Compressive Sensing (CS). As brain voxels have highly
      correlated in spatial domain, the prerequisite of CS methods are not well
      satisfied. We therefore propose a novel MVPA method to integrate linear Sparse
      Bayesian Learning (i.e. Bayesian Compressive Sensing) with random subspace
      method. Benefiting from the random subspace method, spatial correlation and
      feature-to-sample ratio are largely reduced. The experimental results from a real
      fMRI dataset demonstrate that our method has distinct prediction power compared
      to three other popular MVPA methods, and the detected relevant voxels are located
      in informative brain areas. 

PMID- 25570140
TI  - Detection of Alzheimer disease in MR images using structure tensor.
AB  - Alzheimer's disease (AD) is the most common progressive neurodegenerative
      disorder. Therefore, early detection and evaluation of prognosis of AD is an
      important issue in contemporary brain research. Magnetic Resonance Imaging (MRI)
      provides valuable diagnostic information about AD. In this work, brain tissue is
      extracted using phase-based level set method. Structure tensor analysis is used
      to visualize and quantify structural features of the brain from MRI. Further,
      quantitative measures are derived to classify different stages of AD. Normal and
      AD subjects were classified up to an accuracy of 88% using these features. It is
      observed that structural changes in brain can be characterized using this
      technique and therefore can be helpful in tracking the progression of AD and aid
      in classification between normal and AD subjects. 

PMID- 25570143
TI  - Localization of deep brain stimulation electrodes via metal artifacts in CT
      images.
AB  - In Deep Brain Stimulation (DBS), the location of implanted electrodes in the
      brain has direct influence on the therapeutic effect of the treatment. This work
      deals with estimating the position of the implanted DBS electrodes from the
      images registered by X-ray Computed Tomography (CT) scanners. A technique named
      junction method that takes advantage of the streak artifacts created by the metal
      parts of the electrodes in CT images is proposed for this purpose. To start with,
      the brain image is extracted by defining a brain mask. Next, the edges are
      intensified by applying a Gaussian convolution operator followed by a measure of
      the second derivative of the image along all directions in the image plane.
      Criteria of adjacency and length are applied to the lines detected by the Hough
      transform to distinguish between tracks of streak artifacts and the brain
      structure. At some points, straight lines are distorted by noise. To handle this
      issue, all lines that fit same line equation are merged. The horizontal line
      connecting the two DBS electrodes (one in each cerebral hemisphere) is called
      electrode line. To specify the electrodes position, intersections of the
      electrode line with every other line are marked. Finally, to obtain the vertical
      position estimate, the above algorithm is applied to the image stack. 

PMID- 25570142
TI  - Multivariate analysis of structural MRI and PET (FDG and 18F-AV-45) for
      Alzheimer's disease and its prodromal stages.
AB  - A multivariate analysis method, orthogonal partial least squares to latent
      structures (OPLS), was used to discriminate Alzheimer's disease (AD), early and
      late mild cognitive impairment (EMCI and LMCI) from cognitively normal control
      (CN) using MRI and PET measures. FreeSurfer 5.1 generated 271 MRI features
      including 49 subcortical volumes, 68 cortical volumes, 68 cortical thicknesses,
      70 surface areas and 16 hippocampus subfields. Subjects with all aforementioned
      MRI measures passing quality control and valid Fludeoxyglucose (18F) (FDG) and
      Florbetapir (18F) PET scans were selected from ADNI database, resulting in a
      total of 524 participants (137 CN, 214 EMCI, 103 LMCI and 70 AD) for the study.
      Altogether 286 features including 15 significant PET uptake features (7 for FDG
      and 8 for AV-45) were utilized for OPLS analysis. Predictive power was evaluated
      by Q2(Y), a quantifier of the statistical significance for class separation. The
      results show that MRI features (Q2(Y) =0.645), and PET features (Q2(Y) = 0.636)
      has comparable predictive power in separating AD from CN, and MRI features are
      better predictor of LMCI (Q2(Y) = 0.282) than PET (Q2(Y) = 0.294). Combination of
      PET and MRI has the most predictive power for LMCI and AD with Q2(Y) of 0.294 and
      0.721, respectively. While for EMCI, cortical thickness was found to be the best
      predictor with a Q2(Y) of 0.108, suggesting cortical thickness may be the first
      structural change ahead of others and should be prioritized in prediction of very
      mild cognitive impairment.

PMID- 25570141
TI  - Support Vector Machine with nonlinear-kernel optimization for lateralization of
      epileptogenic hippocampus in MR images.
AB  - Surgical treatment is suggested for seizure control in medically intractable
      epilepsy patients. Detailed pre-surgical evaluation and lateralization using
      Magnetic Resonance Images (MRI) is expected to result in a successful surgical
      outcome. In this study, an optimized pattern recognition approach is proposed for
      lateralization of mesial Temporal Lobe Epilepsy (mTLE) patients using asymmetry
      of imaging indices of hippocampus. T1-weighted and Fluid-Attenuated Inversion
      Recovery (FLAIR) images of 76 symptomatic mTLE patients are considered. First,
      hippocampus is segmented using automatic and manual segmentation methods; then,
      volumetric and intensity features are extracted from the MR images. A nonlinear
      Support Vector Machine (SVM) with optimized Gaussian Radial Basis Function (GRBF)
      kernel is used to classify the imaging features. Using leave-one-out cross
      validation, this method results in a correct lateralization rate of 82%, a
      probability of detection for the left side of 0.90 (with false alarm probability
      of 0.04) and a probability of detection for the right side of 0.69 (with zero
      false alarm probability). The lateralization results are compared to linear SVM,
      multi-layer perceptron Artificial Neural Network (ANN), and volumetry and FLAIR
      asymmetry analysis. This lateralization method is suggested for pre-surgical
      evaluation using MRI before surgical treatment in mTLE patients. It achieves a
      more correct lateralization rate and fewer false positives. 

PMID- 25570144
TI  - Hybrid intensity- and phase-based optical flow tracking of tagged MRI.
AB  - Accurate tracking of the myocardium tissues in tagged Magnetic Resonance Images
      (MRI) is essential for evaluating the cardiac function. Current tracking methods
      utilize either the image intensity or the image phase as landmarks that can be
      tracked. In either case, the performance is vulnerable to the image quality and
      the fading of the tag lines. In this work, we propose a hybrid optical flow
      tracking method that combines both the intensity and the phase features of the
      image. The method is validated using numerical cardiac phantom as well as real
      MRI data experiments. Both experiments showed that the proposed method
      outperforms current intensity-based optical flow tracking and the phase-based
      HARP method with maximum error of 1 pixel at extreme conditions of tag fading.

PMID- 25570145
TI  - Automated fetal cardiac valve movement detection for modified myocardial
      performance index calculation.
AB  - The Modified Myocardial Performance Index (Mod-MPI) is becoming an important
      index in fetal cardiac function evaluation. However, the current method for Mod
      MPI calculation can be time-consuming and demonstrates poor inter-operator
      repeatability. This paper presents an automated method for detecting the opening
      and closing events of fetal cardiac valves with the aim of automating the Mod-MPI
      calculation. Fifty-four Doppler ultrasound images, showing blood inflow and
      outflow for the left ventricle, are analyzed to attempt to automatically detect
      the timings of a total of 905 opening and closing events for both aortic and
      mitral valves. Timings are found according to the morphological characteristics
      of waveforms as well as intensity information of images. The proposed method can
      detect the four valve movement events with high sensitivity (95.60-98.64%) and
      precision (96.85-100.00%). Results are verified by comparison with manual
      annotation of same images from an expert.

PMID- 25570146
TI  - The effects of long chain polyunsaturated fatty acids on local activation
      properties in dogs vulnerable to atrial fibrillation.
AB  - Marine derived long chain polyunsaturated fatty acids (PUFAs) were found to have
      benefits in reducing inducibility and maintenance of atrial fibrillation (AF) in
      a dog model. This study was conducted to evaluate the effect of PUFAs on local
      atrial electrical conduction properties acquired via a multi-electrode plaque
      sutured to the posterior wall of the left atrium of the heart in these dogs.
      Eleven dogs underwent simultaneous atrioventricular pacing (SAVP) for 2 weeks,
      and were organized into 2 groups: 5 dogs received no PUFAs (SAVP-PLACEBO), 6 dogs
      received Eicosapentaenoic or Docosahexaenoic acid derived from fish oils (SAVP
      PUFA), where PUFAs were given for 21 days, starting 1 week prior to pacing and
      during the 2 week pacing period. Three features were extracted, which were the
      average conduction velocity, average intra atrial conduction time, and total
      activation time. The PUFA group had a faster average conduction velocity (0.82+/
      0.19 m/s) than the PLACEBO group (0.47+/-0.21 m/s, P=0.02). Using the average
      conduction velocity feature, classification was performed with a linear
      classifier and leave-one-out method. In the SAVP-PLACEBO group, 60% of the dogs
      were correctly classified, and 66% of the dogs were correctly classified in SAVP
      PUFA group, leading to an overall classification accuracy of 63.5%. 

PMID- 25570147
TI  - Quantitative measurement of coronary artery stenosis in CCTA images using a 2D
      parametric intensity model.
AB  - In this paper, we propose an approach based on 2D vessel model to segment the
      vessel lumen in three-dimensional coronary computed tomographic angiography
      (CCTA) images. The 2D parametric intensity model is introduced first to simulate
      the intensity distribution of vessel lumen with different size in the
      longitudinal images. Then the Levenberg-Marquardt method is applied to fit the
      model within a series of region-of interests defined in the longitudinal image.
      The estimated parameters of the model are employed to define the boundary points
      of vessel lumen. The detected boundary points of vessel lumen in six longitudinal
      images are transformed to the cross-sectional planes in order to calculate the
      degree of stenosis according to the luminal areas. Our proposed method was
      evaluated in ten CCTA images with ten reported non-calcified stenosis. The degree
      of each stenosis was computed according to the luminal area and compared with the
      standard reference given by radiologists. Experimental results show that our
      method can estimate the degree of stenosis with a high accuracy.

PMID- 25570148
TI  - A novel approach to quantification of real and artifactual components of current
      density imaging for phantom and live heart.
AB  - Spatial distribution of injected current in a subject could be calculated and
      visualized through current density imaging (CDI). Calculated CDI paths however
      have a limited degree of accuracy due to both avoidable methodological errors and
      inevitable limitations dictated by MR imaging constraints. The source and impact
      of these limitations are scrutinized in this paper. Quantification of such
      limitations is an essential step prior to passing any judgment about the results
      especially in biomedical applications. An innovative technique along with metrics
      for evaluation of range of errors using baseline and phase cycle MR images is
      proposed in this work. The presented approach is helpful in pinpointing the local
      artifacts (areas for which CDI results are suspect), evaluation of global noises
      and artifacts and assessment of the effect of approximation algorithms on real
      and artifactual components. We will demonstrate how this error/reliability
      evaluation is applicable to interpretation of CDI results and in this framework,
      report the CDI results for an artificial phantom and a live pig heart in
      Langendorff setup. It is contended here that using this method, the inevitable
      trade-off between details and approximations of CDI components could be monitored
      which provides a great opportunity for robust interpretation of results. The
      proposed approach could be extended, adapted and used for statistical analysis of
      similar methods which aim at mapping current and impedance based on magnetic flux
      images obtained through MRI. 

PMID- 25570149
TI  - Fully automated assessment of left ventricular volumes and mass from cardiac
      magnetic resonance images.
AB  - Quantification of left ventricular (LV) size and function from cardiac magnetic
      resonance (CMR) images requires manual tracing of LV borders on multiple 2D
      slices, which is subjective, tedious and time-consuming experience. This paper
      presents a fully automated method for endocardial and epicardial boundaries
      detection for the assessment of LV volumes, ejection fraction (EF) and mass from
      CMR images. The segmentation procedure is based on a combined level set approach
      initialized by an automatically detected point inside the LV cavity. To validate
      the proposed technique, myocardial boundaries were manually traced on end
      diastolic (ED) and end-systolic (ES) frames by an experienced cardiologist. Bland
      Altman analysis and linear regression were used to validate LV volumes, EF and
      mass and similarity metrics were applied to assess the agreement between manually
      and automatically detected contours. We found minimal biases and narrow limits of
      agreement for LV volumes, EF and mass; Dice coefficient, Jaccard index and
      Hausdorff distance evaluated for 2D ED and ES endocardial and epicardial
      boundaries showed adequate overlapping. The proposed technique allows fast and
      accurate assessment of LV volumes, EF and mass as a basis for accurate
      quantification of LV size and function, and myocardial scar from CMR images.

PMID- 25570150
TI  - Non-local total variation based low-dose Computed Tomography denoising.
AB  - Radiation dose of X-ray Computed Tomography (CT) imaging has raised a worldwide
      health concern. Therefore, low-dose CT imaging has been of a huge interest in the
      last decade. However, lowering the radiation dose degrades the image quality by
      increasing the noise level, which may reduce the diagnostic performance of the
      images. As a result, image denoising is one of the fundamental tasks in low-dose
      CT imaging. One of the state of art denoising methods, which has been
      successfully used in this area, is Total Variation (TV) denoising. Nevertheless,
      if the parameters of the TV denoising are not optimally adjusted or the algorithm
      is not stopped in an appropriate point, some of the small structures will be
      removed by this method. Here, we provide a solution to this problem by proposing
      a modified nonlocal TV method, called probabilistic NLTV (PNLTV). Denoising
      performance of PNLTV is improved by using better weights and an appropriate
      stopping criterion based on statistics of image wavelet coefficients. Non
      locality allows the algorithm to preserve the image texture, which combined with
      the proposed stopping criterion enables PNLTV to keep fine details unchanged.

PMID- 25570151
TI  - CIDI-lung-seg: a single-click annotation tool for automatic delineation of lungs
      from CT scans.
AB  - Accurate and fast extraction of lung volumes from computed tomography (CT) scans
      remains in a great demand in the clinical environment because the available
      methods fail to provide a generic solution due to wide anatomical variations of
      lungs and existence of pathologies. Manual annotation, current gold standard, is
      time consuming and often subject to human bias. On the other hand, current state
      of-the-art fully automated lung segmentation methods fail to make their way into
      the clinical practice due to their inability to efficiently incorporate human
      input for handling misclassifications and praxis. This paper presents a lung
      annotation tool for CT images that is interactive, efficient, and robust. The
      proposed annotation tool produces an "as accurate as possible" initial annotation
      based on the fuzzy-connectedness image segmentation, followed by efficient manual
      fixation of the initial extraction if deemed necessary by the practitioner. To
      provide maximum flexibility to the users, our annotation tool is supported in
      three major operating systems (Windows, Linux, and the Mac OS X). The
      quantitative results comparing our free software with commercially available lung
      segmentation tools show higher degree of consistency and precision of our
      software with a considerable potential to enhance the performance of routine
      clinical tasks.

PMID- 25570152
TI  - Using Bayesian surprise to detect calcifications in mammogram images.
AB  - Breast Cancer is still a serious health threat to women, both physically and
      psychologically. Fortunately, treatments involving complete breast removal are
      rarely needed today, as better treatment options are available. Mammography can
      show changes in the breast up to two years before a physician can feel them.
      Computer-aided detection and diagnosis is considered to be one of the most
      promising approaches that may improve the efficiency of mammography. Furthermore,
      there is a strong correlation between the presence of calcifications and the
      occurrence of breast cancer. In this paper we present a new technique to detect
      calcifications in mammogram images. The main objective is to support radiologists
      with automatic detection methods applied to medical images. Motivated by the fact
      that calcifications, when compared to the rest of the image, exhibit irregular
      characteristics, a technique based on Bayesian surprise is used. Tests were
      performed using INBreast, a recent fully annotated database, composed of full
      field digital mammograms. Comparison both with a recently proposed state of the
      art method and other common image techniques showed the superiority of our
      method. False positives are, however, still an issue and further studies focused
      on their reduction while maintaining a high sensitivity are planned. 

PMID- 25570153
TI  - Stature of caucasian elderly estimated by scapula length from chest X-ray.
AB  - Stature is an important biological characteristic considered in the clinical
      activities. Height (h)is frequently hard to measure in the elderly population or
      in people with skeletal deformities and vertebral fractures. Furthermore it
      represents also a key point in forensic evaluations. Our aim was to provide an
      equation in order to predict human height based on the Longitudinal Scapular
      Diameter(LSD) measured through a Chest X-ray (CX) in an elderly Italian
      population. We enrolled 60 patients (age > 65 years) who underwent a standard CX.
      An average LSD was obtained on the basis of the measurements of left and right
      scapula. Stature was measured in standard conditions by a calibrated stadiometer
      in all patients. A linear predictive model was employed to estimate stature by
      LSD. The predictive equation for stature estimation [cm] from LSD [cm] was:
      h=2.969*LSD+116.7. The linear regression was significant (p <; 0.01) and the
      correlation coefficient was 0.75. In order to assess the performance of the
      proposed model, we compared our results with the values obtained in the same
      population with a largely employed approach, i.e., the Chumlea's method.
      Considering the whole population, the mean error using LSD equation was 4.4 cm vs
      4.6 cm from Chumlea's. The proposed linear relationship between human height and
      LSD measured by CX can be considered valid in elderly patients, showing
      comparable results to the Chumlea's method.

PMID- 25570154
TI  - Methodology for micro-CT data inflation using intravascular ultrasound images.
AB  - In this paper, a framework for the inflation of micro-CT data using intravascular
      ultrasound (IVUS) images, is presented. The proposed methodology consists of four
      steps. In the first step a centerline is extracted from the micro-CT images. In
      the second step the micro CT images are segmented automatically using the k-means
      algorithm. In the third step IVUS- micro-CT images are co-registered based on
      fiducial markers selected manually by the experts. Finally, the images are
      inflated by applying a transformation method on each image. The transformation
      method is based on the IVUS and micro-CT contour difference. The proposed
      methodology for inflating micro-CT images could increase the reliability of
      correct plaque labeling process as well to enhance the accuracy of the produced
      training dataset from the micro-CT images.

PMID- 25570155
TI  - Material classification of multi-energy CT images using multiple discriminant
      analysis.
AB  - Energy resolved photon-counting detectors could achieve more than one spectral
      measurement. The goal of this study is to investigate, with experiment, the
      ability to decompose five materials using energy discriminating detectors and
      multiple discriminant analysis (MDA). A small field-of-view multi-energy CT
      system was built. Linear attenuation coefficient was considered as features of
      multiple energy CT. MDA was used to decompose five materials with six
      measurements of the energy dependent linear attenuation coefficients. The results
      of the experimental study showed that a CT system based on CdTe detectors with
      MDA can be used to decompose five materials.

PMID- 25570156
TI  - Predicting temperature increase through local SAR estimation by B1 mapping: a
      phantom validation at 7T.
AB  - It has been shown that Electrical Properties d(EPs) of biological tissues can be
      derived from MR-based B1 measurement. A strong appeal for these 'Electrical
      Property Tomography' (EPT) methods is to estimate real-time and subject-specific
      local specific absorption rate (SAR) induced by RF transmission. In order to
      investigate the feasibility of EPT-based local SAR estimation, following
      previously proposed EPT protocols, induced local SAR has been firstly estimated
      under one B1 shim setting for a heating sequence at 7T; whereas with the same
      acquired B1 information, induced local SAR under a different B1 shim setting has
      been further predicted. Both of the SAR results have been compared to measured
      temperature changes using MRI Thermometry based on the proton chemical shift. 

PMID- 25570158
TI  - Realization of magnetic resonance current density imaging at 3 tesla.
AB  - Magnetic Resonance Current Density Imaging (MRCDI) is an imaging modality, which
      reconstructs electrical current density distribution inside a material by using
      Magnetic Resonance Imaging (MRI) techniques. In this study, a current source with
      maximum current injection capability of 224.7mA, under 1kOmega resistive load is
      used. Experiments are performed with a 2D uniform phantom, in which a current
      steering insulator is inserted. Magnetic flux density distributions are measured,
      and current density images are reconstructed. The reconstructed images are in
      agreement with the reconstructions obtained with simulated measurements.

PMID- 25570157
TI  - Investigating the utility of in vivo bio-impedance spectroscopy for the
      assessment of post-ischemic myocardial tissue.
AB  - Increased myocardial structural heterogeneity in response to ischemic injury
      following myocardial infarction (MI) is purported as the mechanism of ventricular
      arrhythmogenesis. Current modalities for in vivo assessment of structural
      heterogeneity for identification of arrhythmogenic substrate are limited due to
      the complex nature of the structural microenvironment post-MI. We investigated
      the utility of in vivo bio-impedance spectroscopy (BIS) in a large post-infarct
      animal model for differentiation between normal and infarcted tissue. We also
      investigated the quantitative effects of adipose and collagen on BIS assessment
      of myocardium. The results indicate that the degree of myocardial injury
      following chronic post-infarction remodeling could be reliably quantified
      (performed in triplicates) using BIS. Furthermore, the presence of
      intramyocardial adipose tissue that develops in conjunction with collagen within
      the infarct zone had a greater and significant influence on BIS then collagen
      tissue alone. These preliminary results indicate a potential role of BIS for
      quantitative assessment and characterization of complex arrhythmogenic substrates
      in ischemic cardiomyopathy.

PMID- 25570159
TI  - Breast tissue phantoms to assist compression study for cancer detection using
      microwave radiometry.
AB  - Microwave radiometry is a passive imaging modality proposed for breast cancer
      detection without the need for ionizing radiation. Detection of breast tumor
      using radiometry is challenging as the intensity of thermal radiation received by
      the antenna is influenced by tumor stage, location, physiological conditions and
      the imaging setup. The controllable parameters for setting up a good imaging
      modality for early detection of breast cancer are ambient temperature (Ta),
      convection cooling of tissue surface (h), and tissue compression (c). Amongst
      these parameters tissue compression plays an important role since reducing the
      breast thickness increases visibility. In this work, fabrication of hydrogel
      breast tissue phantoms with varying concentrations of polyvinyl alcohol (PVAL) is
      carried out to mimic breast fat and glandular tissue properties for compression
      study. The phantoms were subjected to compression to investigate the mechanical
      properties for varying PVAL concentrations. A 3D numerical model was developed
      for phantom tissue compression simulations. Simulated tissue compression results
      were compared with phantom measurements for model validation.

PMID- 25570160
TI  - Dipolar estimates of the cortical map.
AB  - Various methods based on anatomical or mathematical models have been developed to
      estimate cortical potentials. Among them, the most popular are the surface
      Laplacians (SL) and the Electrical Source Imaging (ESI) approaches. In this
      paper, we develop an informed method named dipolar cortical mapping (DCM), aiming
      to find a balance between ESI methods based on anatomical models and methods
      without strong anatomical priors, such as surface Laplacians. Our method only
      uses easily available information on the electrode position and is based on a
      physiologically parametrized family of interpolating functions. Simulation
      results show that DCM competes with previously proposed surface Laplacians and
      with the model based Minimum Norm Estimates (MNE) computed with a Boundary
      Element Model (BEM). 

PMID- 25570161
TI  - Simulation study for a new magnetic induction tomography coil system with weakly
      perturbing in conducting background.
AB  - Biomedical magnetic induction tomography (MIT) aims to reconstruct the passive
      electrical properties within biological tissues, especially the electrical
      conductivity. A weak perturbation inside a conducting object is put in the
      improved MIT coil system which uses the two-arm Archimedean spiral coil as the
      excitation coil and the circular coil as the receiver coil. The forward problem
      for this model is calculated by three-dimension electromagnetic simulation
      experiments. Under the different simulation conditions, the phase shift of
      voltage induced in the receiver coil is compared with that for the common model
      using the circular coil as the excitation and receiver coil. The results show
      that the sensitivity to the improved model is much higher than that to the common
      model except for the case that the perturbation appears in y-axis, which
      effectively confirms the previous conclusions and indicates that the improved
      coil system has the potential advantage for MIT image reconstruction. 

PMID- 25570162
TI  - Breast cancer detection using high-density flexible electrode arrays and
      electrical impedance tomography.
AB  - While mammography remains the gold standard for breast cancer screening,
      additional adjunctive tools for early detection of breast cancer are needed
      especially for young women, women with dense breast tissue and those at increased
      risk due to genetic factors. These patient populations, along with those
      populations for whom mammography is not readily available, require alternative
      technologies capable of effectively detecting breast cancer. One such adjunctive
      modality for breast cancer detection is Electrical Impedance Tomography (EIT). It
      is a non-invasive technique that measures tissue conductivity by injecting a
      small current through a surface electrode while measuring electrode voltage(s).
      The surface measurements are then used to reconstruct a conductivity mapping of
      the tissue. The difference in conductivities between healthy tissue and that of
      carcinoma enable EIT to detect cancer. Electrical Impedance Tomography does not
      subject the patient to ionizing radiation, and offers significant potential for
      detecting very small tumors in early stages of development at a low cost. While
      prior systems have demonstrated success using EIT for breast cancer detection,
      the resolution of the reconstructed image was limited by the spatial resolution
      of the sensing electrode array. Here, we report the use of higher density (3mm
      spacing) flexible micro-electrode arrays to obtain tissue impedance maps.
      Accurate EIT reconstruction is highly dependent on the spatial resolution and
      fidelity of the surface measurements. High-density, flexible arrays that conform
      to the breast surface can offer great potential in reconstructing higher
      resolution conductivity maps than have been previously achieved.

PMID- 25570163
TI  - Real-time 3D electrical impedance imaging for ventilation and perfusion of the
      lung in lateral decubitus position.
AB  - We report a prototype Electrical Impedance Imaging System. It is able to detect
      the gravity-induced changes in the distributions of perfusion and ventilation in
      the lung between supine and lateral decubitus positions. Impedance data were
      collected on healthy volunteer subjects and 3D reconstructed images were produced
      in real-time, 20 frames per second on site, without using averaging or a contrast
      agent. Imaging data also can be reconstructed offline for further analysis.

PMID- 25570164
TI  - J-based Magnetic Resonance Conductivity Tensor Imaging (MRCTI) at 3 T.
AB  - In this study, current density (J) - based Magnetic Resonance Conductivity Tensor
      Imaging (MRCTI) reconstruction algorithms namely, the Anisotropic Equipotential
      Projection (AEPP), the Anisotropic J-Substitution (AJS) and the Anisotropic
      Hybrid J-Substitution (AHJS) algorithms are implemented to reconstruct
      conductivity tensor images of a physical phantom using a 3T magnetic resonance
      imaging system. 10mA current pulses are injected in synchrony with a conventional
      spin-echo pulse sequence. Furthermore, a new J-based hybrid algorithm namely, the
      Anisotropic Hybrid Equipotential Projection (AHEPP) is proposed. In addition,
      reconstruction performances of the four algorithms are evaluated.

PMID- 25570165
TI  - Induced current magnetic resonance electrical impedance tomography with z
      gradient coil.
AB  - Magnetic Resonance Electrical Impedance Tomography (MREIT) is a medical imaging
      method that provides images of electrical conductivity at low frequencies (0-1
      kHz). In MREIT, electrical current is applied to the body via surface electrodes
      and corresponding magnetic flux density is measured by means of Magnetic
      Resonance (MR) phase imaging techniques. By utilizing the magnetic flux density
      measurements and surface potential measurements images of true conductivity
      distribution can be reconstructed. In order to overcome difficulties regarding
      current application via surface electrodes, Induced Current MREIT (ICMREIT) have
      been proposed in the past. In ICMREIT, electrical currents and corresponding
      magnetic flux density are generated in the object through electromagnetic
      induction by means of externally placed coils driven with time varying currents.
      In this study, use of z-gradient, z-Helmholtz, and circular coil configurations
      in ICMREIT are proposed and investigated. Finite Element Method (FEM) is used to
      solve the forward problem of ICMREIT. Consequently, excitation performances and
      clinical applicability of different coil configurations are analyzed.

PMID- 25570166
TI  - Influence of the stereo-EEG sensors setup and of the averaging on the dipole
      localization problem.
AB  - While scalp EEG/MEG source imaging have been extensively studied in the last two
      decades, the case of source localization from invasive measurements has resulted
      in few works to date. Yet there is a lot to gain from stereo
      electroencephalographic (SEEG) recordings, providing high signal to noise ratio
      measurements of the explored brain structures. The SEEG setup consists in multi
      contact electrodes inserted in the brain volume, each containing a dozen of
      collinear measuring contacts. This particular setup raises the question of the
      conditioning of the inverse problem. In recent works, we have evaluated the
      feasibility to localize a single dominant equivalent dipole facing different
      sensors and noise configurations. We deepen here the analysis by evaluating the
      influence of the chosen subset of sensors and of the number of averaged time
      samples on the accuracy of the localization. We conduct experiments on simulated
      data as well as on real epileptic spikes, illustrating the trade off to be made
      between these two factors.

PMID- 25570167
TI  - Pathway-based expression profile for breast cancer diagnoses.
AB  - Microarray experiments have made possible to identify breast cancer marker gene
      signatures. However, gene expression-based signatures present limitations because
      they do not consider metabolic role of the genes and are affected by genetic
      heterogeneity across patient cohorts. Considering the activity of entire pathways
      rather than the expression levels of individual genes can be a way to exceed
      these limits. We evaluated and compared five methods of pathway-level aggregation
      of gene expression data. Our results confirmed the important role of pathway
      expression profile in breast cancer diagnostic classification (accuracy >90%).
      However, although assessed on a limited number of samples and datasets, this
      study shows that using dissimilarity representation among patients does not
      improve the classification of pathway-based expression profiles.

PMID- 25570168
TI  - A comparison between direct and indirect measurements of neurotransmitter vesicle
      release dynamics: a computational study.
AB  - Presynaptic vesicular release of neurotransmitters is a stochastic process
      involving complex mechanisms triggered by an elevation of calcium concentration.
      The mechanisms behind neurotransmitters release play a critical role in synaptic
      function and plasticity. Understanding its properties, both in term of its
      dynamics and its underlying mechanisms, may therefore help further our
      understanding of synaptic plasticity. However, measuring vesicle release dynamics
      is experimentally challenging. One experimental protocol used to determine the
      dynamic properties of vesicle release is to measure postsynaptic current.
      However, this method inherently not only captures properties of the release
      itself, but also the contributions from the postsynaptic receptors. Here we
      propose to use a synapse simulation platform known as EONS/RHENOMS to capture the
      functional properties of vesicle release, separate from the dynamics known to be
      associated with postsynaptic receptors, and compare the results with those
      determined experimentally. We find that despite attempts to reduce interference
      of postsynaptic dynamics, the receptor channel properties, particularly
      desensitization, may influence the overall measured results significantly. Re
      estimating release rate by taking into account the contributions of postsynaptic
      receptors may give further insight into release dynamics and further our overall
      understanding on synaptic plasticity.

PMID- 25570169
TI  - In silico Kinetic Model of iNOS expression in macrophages.
AB  - Macrophages are a key component in the host innate response and are major
      contributors to the proinflammatory response against pathogens. One of the key
      players in the proinflammatory response is induced nitric oxide synthase (iNOS),
      an enzyme that provides the nitric oxide needed by phagocytic cells to create
      reactive nitrogen species, which are highly damaging to intracellular pathogens.
      To model the macrophage intracellular mechanism of iNOS gene expression, we use a
      systems biology approach to capture the dynamics of the iNOS gene expression
      system stimulated by bacterial lipopolysaccharide (LPS) and IFN-gamma. Our
      simulation results agree with in vitro assays of iNOS gene expression and provide
      a platform for further investigating the potential impact of LPS and IFN-gamma
      variations on macrophage effector function.

PMID- 25570170
TI  - Homo-oligomerization of transmembrane alpha-domain of integrin.
AB  - Integrins contribute to form focal adhesions complex. Therefore, simulation of
      integrin interactions can be helpful in clarifying the mechanism of focal
      adhesion formation. Interactions of integrins can also initiate signal
      transduction in the focal adhesions. Since integrins contain alpha and beta
      subunits that are separated in an active state, studying both subunits separately
      is crucial, since, in the active state of integrins, the distance between these
      subunits is long enough that they do not influence one another significantly.
      Thus, this study aims to investigate the tendency of alpha subunits of integrins
      to form homodimers. All simulations were carried out via MARTINI coarse grain
      (CG) molecular dynamics technique. alpha subunits were placed in 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer at a distance of 5 nm,
      and they were allowed to diffuse in the lipid bilayer. All simulations showed
      that alpha subunits have a tendency to form stable dimers. 

PMID- 25570172
TI  - Synthesis of optimal control of complex biological pathways enabled by global
      sensitivity analysis.
AB  - The past few years have witnessed growth in the number of system biological
      models corresponding to several different pathways and have shed light on
      biological processes governing vital functions such as signal transduction, cell
      proliferation and cell-apoptosis. Among several challenges in modeling and
      verification, significant efforts have been made in system identification
      including model parameter estimation and key component identification. In a
      practical or experimental setting, the effects of various control strategies, are
      usually associated with costs including enzyme consumption or the desired levels
      of output transcription. In this work we address the problem of designing an
      optimal control law via a combination of computational tools such as sensitivity
      analysis, Pontryagin maximum principle and steepest descent technique. We find
      that, in the presence of limitation of enzyme concentration level control,
      optimal control law can be developed only by choosing enzyme with dominant effect
      on dynamical behavior of biological pathway. In this work, we study JAK/STAT
      signal transduction pathway, and by simulation analysis, we investigate the
      effectiveness of Sobol values in developing optimal control law. 

PMID- 25570173
TI  - Platform for the study of virtual task-oriented motion and its evaluation by EEG
      and EMG biopotentials.
AB  - This paper presents a platform to study the relationship between upper limb
      kinematic and biopotential measurements. The platform comprises of a haptic
      joystick, biopotential acquisition systems and 3D rendered virtual tasks that
      require user interaction. The haptic joystick, named TeeR, reproduces the
      pronation-supination and flexion-extension movements of the human arm, which are
      directly mapped to a 2D graphic display. The biopotential acquisition system is
      able to record electroencephalography (EEG) and electromyography (EMG) signals
      and synchronize them with kinematic data obtained from the Tee-R. The 3D virtual
      tasks are designed to obtain performance measurements from the user interaction.
      We include an example that depicts the possibilities of application for the study
      of event-related (de)synchronization (ERD/ERS) based on EEG during motor tasks. 

PMID- 25570171
TI  - Roles of regulated internalization in the polarization of cell surface receptors.
AB  - Cell polarization, the generation of cellular asymmetries, is a fundamental
      biological process. Polarity of different molecules can arise through several
      mechanisms. Among these, internalization has been shown to play an important role
      in the polarization of cell surface receptors. The internalization of cell
      surface receptors can be upregulated upon ligand binding. Additional regulatory
      mechanism can downregulate the internalization process. Here we describe a
      general model, which incorporates these two opposing processes, to study the role
      of internalization in the establishment of cell polarity. We find that the
      competition between these two processes is sufficient to induce receptor
      polarization. Our results show that regulated internalization provides additional
      regulation on polarization as well. In addition, we discuss applications of our
      model to the yeast system, which shows the capability and potential of the model.

PMID- 25570175
TI  - Design of a portable hydraulic ankle-foot orthosis.
AB  - Small-scale hydraulics is ideal for powered human assistive devices including
      powered ankle foot orthoses because a large torque can be generated with an
      actuator that is small and light. A portable hydraulic ankle foot orthosis has
      been designed and is undergoing preliminary prototyping and engineering bench
      test evaluation. The device provides 90 Nm of ankle torque and has an operating
      pressure of 138 bar (2,000 psi). The battery-operated hydraulic power supply
      weighs about 3 kg and is worn at the waist. The ankle component weighs about 1.2
      Kg and connects to the power supply with two hoses. Performance simulation and
      preliminary bench testing suggests that the device could be useful in certain
      rehabilitation applications. 

PMID- 25570174
TI  - Multisensory interface for 5D stem cell image volumes.
AB  - Biological imaging of live cell and tissue using 3D microscopy is able to capture
      time-lapse image sequences showing multiple molecular markers labeling different
      biological structures simultaneously. In order to analyze this complex multi
      dimensional image sequence data, there is a need for automated quantitative
      algorithms, and for methods to visualize and interact with both the data and the
      analytical results. Traditional computational human input devices such as the
      keyboard and mouse are no longer adequate for complex tasks such as manipulating
      and navigating 3+ dimensional volumes. In this paper, we have developed a new
      interaction system for interfacing with big data sets using the human visual
      system together with touch, force and audio feedback. This system includes real
      time dynamic 3D visualization, haptic interaction via exoskeletal glove, and
      tonal auditory components that seamlessly create an immersive environment for
      efficient qualitative analysis. 

PMID- 25570176
TI  - Position versus force control: using the 2-DOF robotic ankle trainer to assess
      ankle's motor control.
AB  - An estimated of 2,000,000 acute ankle sprains occur annually in the United
      States. Furthermore, ankle disabilities are caused by neurological impairments
      such as traumatic brain injury, cerebral palsy and stroke. The virtually
      interfaced robotic ankle and balance trainer (vi-RABT) was introduced as a cost
      effective platform-based rehabilitation robot to improve overall ankle/balance
      strength, mobility and control. The system is equipped with 2 degrees of freedom
      (2-DOF) controlled actuation along with complete means of angle and torque
      measurement mechanisms. Vi-RABT was used to assess ankle strength, flexibility
      and motor control in healthy human subjects, while playing interactive virtual
      reality games on the screen. The results suggest that in the task with 2-DOF,
      subjects have better control over ankle's position vs. force.

PMID- 25570177
TI  - An advanced control strategy of an electrical--powered hospital bed.
AB  - This paper develops a multivariable control technique for low-level control of an
      intelligent hospital bed. First, multivariable hospital bed models, nominal,
      upper bounded and lower bounded models, are obtained via an experimental
      identification procedure. Based on the obtained nominal model, the triangular
      diagonal dominance (TDD) decoupling technique is applied to reduce a complex
      multivariable system into a series of scalar systems. For each scalar system, an
      online adaptive control strategy is then developed to cope with system
      uncertainties. Compared to the conventional control method, real-time
      experimental results showed that our proposed multivariable control technique
      achieved better performance. Experimental results also confirmed that desirable
      system performance was guaranteed under system uncertainty conditions. 

PMID- 25570178
TI  - Task-oriented robot-assisted stroke therapy of paretic limb improves control in a
      unilateral and bilateral functional drink task: a case study.
AB  - The purpose of this paper is to evaluate the functional, temporal and spatial
      effect of a unilateral task-oriented, robot-assisted training on unilateral and
      bilateral task performance of a drinking task using a real object. Two chronic
      stroke survivors experienced task-oriented robot assisted therapy, in which the
      paretic arm was trained using reaching and grasping tasks over 4 weeks. Both
      subjects experienced improvement in motor control as measured by Fugl-Meyer. The
      paretic arm was evaluated using movement smoothness (MS) and time to completion
      (TCT) measures before and after therapy. From the results, we found that the
      unilateral robotassisted training improved paretic arm control in the unilateral
      and the bilateral drink task. However, the influence of the non-paretic movement
      on the temporal and spatial paretic arm control was evident both pre and post
      therapy suggesting inter-limb coupling aids in the transfer of unilateral
      improvements in motor control to improvements in bilateral motor control. 

PMID- 25570179
TI  - Monocular camera and IMU integration for indoor position estimation.
AB  - This paper presents a monocular camera (MC) and inertial measurement unit (IMU)
      integrated approach for indoor position estimation. Unlike the traditional
      estimation methods, we fix the monocular camera downward to the floor and collect
      successive frames where textures are orderly distributed and feature points
      robustly detected, rather than using forward oriented camera in sampling unknown
      and disordered scenes with pre-determined frame rate and auto-focus metric scale.
      Meanwhile, camera adopts the constant metric scale and adaptive frame rate
      determined by IMU data. Furthermore, the corresponding distinctive image feature
      point matching approaches are employed for visual localizing, i.e., optical flow
      for fast motion mode; Canny Edge Detector & Harris Feature Point Detector & Sift
      Descriptor for slow motion mode. For superfast motion and abrupt rotation where
      images from camera are blurred and unusable, the Extended Kalman Filter is
      exploited to estimate IMU outputs and to derive the corresponding trajectory.
      Experimental results validate that our proposed method is effective and accurate
      in indoor positioning. Since our system is computationally efficient and in
      compact size, it's well suited for visually impaired people indoor navigation and
      wheelchaired people indoor localization. 

PMID- 25570180
TI  - Assessment of walking speed by a goniometer-based method.
AB  - A quantitative gait analysis is essential to evaluate the kinematic, kinetic and
      electromyographic gait patterns. These patterns are strongly related to the
      individual spatio-temporal parameters that characterize each subject. In
      particular, gait speed is one of the most important spatio-temporal gait
      parameters: it influences kinematic, kinetic parameters, and muscle activity too.
      The aim of the present study is to propose a new method to assess stride speed
      using only 1-degree-of-freedom electrogoniometers positioned on hip and knee
      joints. The model validation is performed comparing the model results with those
      automatically obtained from another gait analysis system: GAITRite. The results
      underline the model reliability. These results show that essential spatio
      temporal gait parameters, and in particular the speed of each stride, can be
      determined during normal walking using only two 1-dof electrogoniometers. The
      method is easy-to-use and does not interfere with regular walking patterns. 

PMID- 25570181
TI  - An objective index to estimate the survival rate of primary blast lung injury.
AB  - To supply proper treatments to the primary blast lung injury (PBLI) patients, it
      is important to estimate the severity of the primary blast lung injury in
      accordance with the blast conditions. In this study, a blast-induced mechanical
      parameter (first principal stress) of lung was calculated using a finite element
      thorax model and the correlation between the survival rate of the subjects with
      blast-induced lung damage and an objective index that was related to the first
      principal stress of the lung model. This study propose the objective index for
      the estimation of the degree of PBLI. The results have a potential clinical
      application to improve the efficacy of treatment for blast injury patients. 

PMID- 25570182
TI  - Assessing neuromuscular mechanisms in human-exoskeleton interaction.
AB  - In this study, we propose to evaluate a 7 DOF exoskeleton in terms of motion
      control. Using criteria from the human motor control literature, inverse
      optimization was performed to assess an industrial screwing movement. The results
      of our study show that the hybrid composition of the free arm movement was
      accurately determined. At contrary, when wearing the exoskeleton, which produces
      an arbitrary determined torque compensation, the motion is different from the
      naturally adopted one. This study is part of the evaluation and comprehension of
      the complex neuromuscular mechanism resulting in wearing an exoskeleton several
      hours per day for industrial tasks assistance. 

PMID- 25570183
TI  - Changes of Achilles tendon properties via 12-week PNF based robotic
      rehabilitation of ankle joints with spasticity and/or contracture.
AB  - Ankle joint with spasticity and/or contracture can severely affect mobility and
      independence of stroke survivors. Due to that, the Achilles tendon(AT) is
      affected. In this paper, we aim to study changes of AT properties via
      proprioceptive neuromuscular facilitation (PNF) treatment. A robotic ankle-foot
      rehabilitation system has been proposed, which consists of a robotic ankle-foot
      platform and a graphic user interface. In this pilot study, two post-stroke
      patients participated and carried out a 12-week PNF treatment with the robotic
      system. The treatment is evaluated quantitatively in AT properties. The
      evaluation shows that after the PNF treatment, the average decrease of AT length
      is 4.1 mm (6.5%) and the recovery ratio is 30.4%, while the thickness has no
      change. The results indicate that the PNF based robotic rehabilitation for ankle
      joints with spasticity and/or contracture is effective to improve the ankle
      spasticity/contracture.

PMID- 25570184
TI  - Proposal of bioinstrumentation using flex sensor for amputated upper limb.
AB  - We previously proposed a new bioinstrumentation using the shape deformation of
      the amputated upper limbs without using the myoelectricity generated on the skin
      of the upper limbs. However many electronic parts were required owing to a bridge
      circuit and multi-amplifier circuits so as to amplify a tiny voltage of strain
      gages. Moreover, the surplus heat might occur by the overcurrent owing to low
      resistance value of strain gages. Therefore, in this study, we apply a flex
      sensor to this system instead of strain gages to solve the above problems.

PMID- 25570185
TI  - CLINATEC(r) BCI platform based on the ECoG-recording implant WIMAGINE(r) and the
      innovative signal-processing: preclinical results.
AB  - The goal of the CLINATEC(r) Brain Computer Interface (BCI) Project is to improve
      tetraplegic subjects' quality of life by allowing them to interact with their
      environment through the control of effectors, such as an exoskeleton. The BCI
      platform is based on a wireless 64-channel ElectroCorticoGram (ECoG) recording
      implant WIMAGINE(r), designed for long-term clinical application, and a BCI
      software environment associated to a 4-limb exoskeleton EMY (Enhancing MobilitY).
      Innovative ECoG signal decoding algorithms will allow the control of the
      exoskeleton by the subject's brain activity. Currently, the whole BCI platform
      was tested in real-time in preclinical experiments carried out in nonhuman
      primates. In these experiments, the exoskeleton arm was controlled by means of
      the decoded neuronal activity.

PMID- 25570186
TI  - Optimizing visual-to-auditory delay for multimodal BCI speller.
AB  - Multimodal spellers combining visual and auditory stimulation have recently
      gained more attention in ERP-based Brain-Computer Interfaces (BCIs). Most studies
      found an improved efficiency compared to unimodal paradigms while few have
      explored the effect of the visual-to-auditory delays on the spelling performance.
      Here, we study five conditions with different visual-to-auditory delays, in order
      to find the paradigm that provides the best overall BCI performance. We compared
      the temporal and spatial binary classification accuracy as well as the grand
      averaged classification accuracies over repetitions. Results show that long
      delays may cause better performance in early time intervals corresponding to
      negative ERP components, but better overall performance is achieved with short
      visual-to-auditory delays. 

PMID- 25570187
TI  - Low cost implementation of a Motor Imagery experiment with BCI system and its use
      in neurorehabilitation.
AB  - The application of rehabilitation programs based on videogames with brain
      computer interfaces (BCI) allows to provide feedback to the user with the
      expectation of stimulate the brain plasticity that will restore the motor
      control. The use of specific mental strategies such as Motor Imagery (MI) in
      neuroscientific experiments with BCI systems often requires the acquisition of
      sophisticated interfaces and specialized software for execution, which usually
      have a high implementation costs. We present a combination of low-cost hardware
      and open-source software for the implementation of videogame based on virtual
      reality with MI and its potential use as neurotherapy for stroke patients. Three
      machine learning algorithms for the BCI signals classification are shown: LDA
      (Linear Discriminant Analysis) and two Support Vector Machines (SVM) in order to
      determine which task of MI is being performed by the user in a particular moment
      of the experiment. All classification algorithms was evaluated in 8 healthy
      subjects, the average accuracy of the best classifier was 96.7%, which shows that
      it is possible to carry out serious neuroscientific experiments with MI using low
      cost BCI systems and achieve comparable accuracies with more sophisticated and
      expensive devices.

PMID- 25570188
TI  - Comparison of steady-state visual and somatosensory evoked potentials for brain
      computer interface control.
AB  - Many proposed EEG-based brain-computer interfaces (BCIs) make use of visual
      stimuli to elicit steady-state visual evoked potentials (SSVEP), the frequency of
      which can be mapped to a computer input. However, such a control scheme can be
      ineffective if a user has no motor control over their eyes and cannot direct
      their gaze towards a flashing stimulus to generate such a signal. Tactile-based
      methods, such as somatosensory steady-state evoked potentials (SSSEP), are a
      potentially attractive alternative in these scenarios. Here, we compare the
      neural signals elicited by SSSEP to those elicited by SSVEP in naive BCI users
      towards evaluating the feasibility of SSSEP-based control of an EEG BCI.

PMID- 25570189
TI  - Brain-computer interface driven functional electrical stimulation system for
      overground walking in spinal cord injury participant.
AB  - The current treatment for ambulation after spinal cord injury (SCI) is to
      substitute the lost behavior with a wheelchair; however, this can result in many
      co-morbidities. Thus, novel solutions for the restoration of walking, such as
      brain-computer interfaces (BCI) and functional electrical stimulation (FES)
      devices, have been sought. This study reports on the first electroencephalogram
      (EEG) based BCI-FES system for overground walking, and its performance assessment
      in an individual with paraplegia due to SCI. The results revealed that the
      participant was able to purposefully operate the system continuously in real
      time. If tested in a larger population of SCI individuals, this system may pave
      the way for the restoration of overground walking after SCI.

PMID- 25570190
TI  - Electrocorticogram encoding of upper extremity movement duration.
AB  - Electrocorticogram (ECoG) is a promising long-term signal acquisition platform
      for brain-computer interface (BCI) systems such as upper extremity prostheses.
      Several studies have demonstrated decoding of arm and finger trajectories from
      ECoG high-gamma band (80-160 Hz) signals. In this study, we systematically vary
      the velocity of three elementary movement types (pincer grasp, elbow and shoulder
      flexion/extension) to test whether the high-gamma band encodes for the entirety
      of the movements, or merely the movement onset. To this end, linear regression
      models were created for the durations and amplitudes of high-gamma power bursts
      and velocity deflections. One subject with 8*8 high-density ECoG grid (4 mm
      center-to-center electrode spacing) participated in the experiment. The results
      of the regression models indicated that the power burst durations varied directly
      with the movement durations (e.g. R(2)=0.71 and slope=1.0 s/s for elbow). The
      persistence of power bursts for the duration of the movement suggests that the
      primary motor cortex (M1) is likely active for the entire duration of a movement,
      instead of providing a marker for the movement onset. On the other hand, the
      amplitudes were less co-varied. Furthermore, the electrodes of maximum R(2)
      conformed to somatotopic arrangement of the brain. Also, electrodes responsible
      for flexion and extension movements could be resolved on the high-density grid.
      In summary, these findings suggest that M1 may be directly responsible for
      activating the individual muscle motor units, and future BCI may be able to
      utilize them for better control of prostheses.

PMID- 25570191
TI  - Brain-controlled functional electrical stimulation for lower-limb motor recovery
      in stroke survivors.
AB  - Despite the prevalence of stroke-induced gait impairment due to foot drop,
      current rehabilitative practices to improve gait function are limited, and
      orthoses can be uncomfortable and do not provide long-lasting benefits.
      Therefore, novel modalities that may facilitate lasting neurological and
      functional improvements, such as brain-computer interfaces (BCIs), have been
      explored. In this article, we assess the feasibility of BCI-controlled functional
      electrical stimulation (FES) as a novel physiotherapy for post-stroke foot drop.
      Three chronic stroke survivors with foot drop received three, 1-hour sessions of
      therapy during 1 week. All subjects were able to purposefully operate the BCI-FES
      system in real time. Furthermore, the salient electroencephalographic (EEG)
      features used for classification by the data-driven methodology were determined
      to be physiologically relevant. Over the course of this short therapy, the
      subjects' dorsiflexion active range of motion (AROM) improved by 3 degrees , 4
      degrees , and 8 degrees , respectively. These results indicate that chronic
      stroke survivors can operate the BCI-FES system, and that BCI-FES intervention
      may promote functional improvements.

PMID- 25570192
TI  - Computationally efficient feature denoising filter and selection of optimal
      features for noise insensitive spike sorting.
AB  - Feature extraction is a critical step in real-time spike sorting after a spike is
      detected. Features should be informative and noise insensitive for high
      classification accuracy. This paper describes a new feature extraction method
      that utilizes a feature denoising filter to improve noise immunity while
      preserving spike information. Six features were extracted from filtered spikes,
      including a newly developed feature, and a separability index was applied to
      select optimal features. Using a set of the three highest-performing features,
      which includes the new feature, this method can achieve spike classification
      error as low as 5% for the worst case noise level of 0.2. The computational
      complexity is only 11% of principle component analysis method and it only costs
      nine registers per channel.

PMID- 25570193
TI  - Influence of mental fatigue on P300 and SSVEP during virtual wheelchair
      navigation.
AB  - The aim of this paper is to investigate the influence of mental fatigue on
      Positive 300 (P300) and Steady State Visual Evoked Potentials (SSVEP) during
      virtual wheelchair navigation. For this purpose, experimental protocols were
      setup in order to induce mental fatigue, P300 and SSVEP. Next, the correlation
      between mental fatigue and P300/SSVEP parameters were investigated. At the end,
      the best correlated features from both modalities were used as inputs for three
      classification techniques. Depending on the subject samples (healthy vs palsy),
      The best overall classification rate reached 80% for P300 modality. The results
      of this investigation constitute the first steps towards an anticipatory system
      that can assist the wheelchair driver during navigation, depending on his mental
      fatigue level. 

PMID- 25570194
TI  - Subject-oriented training for motor imagery brain-computer interfaces.
AB  - Successful operation of motor imagery (MI)-based brain-computer interfaces (BCI)
      requires mutual adaptation between the human subject and the BCI. Traditional
      training methods, as well as more recent ones based on co-adaptation, have mainly
      focused on the machine-learning aspects of BCI training. This work presents a
      novel co-adaptive training protocol shifting the focus on subject-related
      performances and the optimal accommodation of the interactions between the two
      learning agents of the BCI loop. Preliminary results with 8 able-bodied
      individuals demonstrate that the proposed method has been able to bring 3 naive
      users into control of a MI BCI within a few runs and to improve the BCI
      performances of 3 experienced BCI users by an average of 0.36 bits/sec.

PMID- 25570195
TI  - Classification of finger pairs from one hand based on spectral features in human
      EEG.
AB  - Individual finger movements are well-articulated movements of fine body parts,
      the successful decoding of which can provide extra degrees of freedom to drive
      brain computer interface (BCI) applications. Past studies present some unique
      features revealed from spectral principal component analysis (PCA) on
      electrophysiological data recorded in both the surface of the brain
      (electrocorticography, ECoG) and the scalp (electroencephalography, EEG). These
      features contain discriminable information about fine individual finger movements
      from one hand. However, the efficacy of these spectral features has not been well
      investigated under the application of various classifiers. In the present study,
      we set out to investigate the topic using noninvasive human EEG. Several
      classifiers were chosen to explore their capability in capturing the spectral PC
      features to decode individual finger movements pairwisely from one hand using
      noninvasive EEG, aiming to investigate the efficacy of these spectral features in
      a decoding task.

PMID- 25570196
TI  - A new descriptor of neuroelectrical activity during BCI-assisted motor imagery
      based training in stroke patients.
AB  - In BCI applications for stroke rehabilitation, BCI systems are used with the aim
      of providing patients with an instrument that is capable of monitoring and
      reinforcing EEG patterns generated by motor imagery (MI). In this study we
      proposed an offline analysis on data acquired from stroke patients subjected to a
      BCI-assisted MI training in order to define an index for the evaluation of MI-BCI
      training session which is independent from the settings adopted for the online
      control and which is able to describe the properties of neuroelectrical
      activations across sessions. Results suggest that such index can be adopted to
      sort the trails within a session according to the adherence to the task. 

PMID- 25570197
TI  - Modulation effect of transcranial direct current stimulation on phase
      synchronization in motor imagery brain-computer interface.
AB  - Transcranial direct current stimulation (tDCS) has been demonstrated that it can
      enhance the cortex excitability and modulate the event-related desynchronization
      (ERD) in motor imagery (MI). Phase synchronization is an important signature in
      the brain that reflects the neural interaction and integration, which has been
      adopted as an important EEG pattern for Brian-Computer Interface (BCI) control.
      In this study, we designed an experiment paradigm and investigated whether the
      tDCS can modulate the phase synchronization between the primary motor cortex (M1)
      and the supplementary motor area (SMA) in MI. Ten healthy subjects were selected
      and separated into two groups randomly. They performed the left and right hand MI
      task in two successive sessions. According to the different groups, anodal or
      sham stimulation were administrated to the right side of the M1. The phase
      locking value (PLV), which is a reliable measurement of phase synchronization in
      MI, was calculated. The pre and post-stimulation normalized PLV in the left hand
      MI task were compared. The result manifests that the normalized PLV of the entire
      subjects in anodal stimulation group increases after the stimulation, which shows
      a statistically significant difference (paired t-test p = 0.0371, n = 5). Our
      study reveals that the tDCS can impact the neural coupling between different
      brain regions and modulate phase synchronization in MI. Moreover, intervention of
      phase synchronization by tDCS might contribute to the rehabilitation of people
      with motor disorder and neurological disorders.

PMID- 25570198
TI  - Energy efficient acquisition and reconstruction of EEG signals.
AB  - In Wireless Body Area Networks (WBAN) the energy consumption is dominated by
      sensing and communication. Previous Compressed Sensing (CS) based solutions to
      EEG tele-monitoring over WBAN's could only reduce the communication cost. In this
      work, we propose a matrix completion based formulation that can also reduce the
      energy consumption for sensing. We test our method with state-of-the-art CS based
      techniques and find that the reconstruction accuracy from our method is
      significantly better and that too at considerably less energy consumption. Our
      method is also tested for post-reconstruction signal classification where it
      outperforms previous CS based techniques. At the heart of the system is an Analog
      to Information Converter (AIC) implemented in 65nm CMOS technology. The
      pseudorandom clock generator enables random under-sampling and subsequent
      conversion by the 12-bit Successive Approximation Register Analog to Digital
      Converter (SAR ADC). AIC achieves a sample rate of 0.5 KS/s, an ENOB 9.54 bits,
      and consumes 108 nW from 1 V power supply.

PMID- 25570199
TI  - Decoding of Chinese phoneme clusters using ECoG.
AB  - A finite set of phonetic units is used in human speech, but how our brain
      recognizes these units from speech streams is still largely unknown. The
      revealing of this neural mechanism may lead to the development of new types of
      speech brain computer interfaces (BCI) and computer speech recognition systems.
      In this study, we used electrocorticography (ECoG) signal from human cortex to
      decode phonetic units during the perception of continuous speech. By exploring
      the wavelet time-frequency features, we identified ECoG electrodes that have
      selective response to specific Chinese phonemes. Gamma and high-gamma power of
      these electrodes were further combined to separate sets of phonemes into
      clusters. The clustered organization largely coincided with phonological
      categories defined by the place of articulation and manner of articulation. These
      findings were incorporated into a decoding framework of Chinese phonemes
      clusters. Using support vector machine (SVM) classifier, we achieved consistent
      accuracies higher than chance level across five patients discriminating specific
      phonetic clusters, which suggests a promising direction of implementing a speech
      BCI.

PMID- 25570200
TI  - Single-trial classification of neural responses evoked in rapid serial visual
      presentation: effects of stimulus onset asynchrony and stimulus repetition.
AB  - Rapid serial visual presentation (RSVP) tasks, in which participants are
      presented with a continuous sequence of images in one location, have been used in
      combination with electroencephalography (EEG) in a variety of Brain-Machine
      Interface (BMI) applications. The RSVP task is advantageous because it can be
      performed at a high temporal rate. The rate of the RSVP sequence is controlled by
      the stimulus onset asynchrony (SOA) between subsequent stimuli. When used within
      the context of a BMI, an RSVP task with short SOA could increase the information
      throughput of the system while also allowing for stimulus repetitions. However,
      reducing the SOA also increases the perceptual degradation caused by presenting
      two stimuli in close succession, and it decreases the target-to-target interval
      (TTI), which can increase the cognitive demands of the task. These negative
      consequences of decreasing the SOA could affect on the EEG signal measured in the
      task and degrade the performance of the BMI. Here we systematically investigate
      the effects of SOA and stimulus repetition (r) on single-trial target detection
      in an RSVP task. Ten healthy volunteers participated in an RSVP task in four
      conditions that varied in SOA and repetitions (SOA=500 ms, r=1; SOA=250 ms, r=2;
      SOA=166 ms, r=3; and SOA=100 ms, r=5) while processing time across conditions was
      controlled. There were two key results: First, when controlling for the number of
      repetitions, single-trial performance increases when the SOA decreases. Second,
      when the repetitions were combined, the best performance (AUC=0.967) was obtained
      with the shortest SOA (100 ms). These results suggest that shortening the SOA in
      an RSVP task has the benefit of increasing the performance relative to longer
      SOAs, and it also allows a higher number of repetitions of the stimuli in a
      limited amount of time.

PMID- 25570201
TI  - Write, read and answer emails with a dry 'n' wireless brain-computer interface
      system.
AB  - Brain-computer interface (BCI) users can control very complex applications such
      as multimedia players or even web browsers. Therefore, different biosignal
      acquisition systems are available to noninvasively measure the electrical
      activity of the brain, the electroencephalogram (EEG). To make BCIs more
      practical, hardware and software are nowadays designed more user centered and
      user friendly. In this paper we evaluated one of the latest innovations in the
      area of BCI: A wireless EEG amplifier with dry electrode technology combined with
      a web browser which enables BCI users to use standard webmail. With this system
      ten volunteers performed a daily life task: Write, read and answer an email.
      Experimental results of this study demonstrate the power of the introduced BCI
      system.

PMID- 25570202
TI  - Investigation into machine learning algorithms as applied to motor cortex signals
      for classification of movement stages.
AB  - Neuroinformatics has recently emerged as a powerful field for the statistical
      analysis of neural data. This study uses machine learning techniques to analyze
      neural spiking activities within a population of neurons with the aim of finding
      spiking patterns associated with different stages of movement. Neural data was
      recorded during many experimental trials of a cat performing a skilled reach and
      withdrawal task. Using Weka and the LibSVM classifier, movement stages of the
      skilled task were identified with a high degree of certainty achieving an area
      under-curve (AUC) of the Receiver Operating Characteristic of between 0.900 and
      0.997 for the combined data set. Through feature selection, the identification of
      significant neurons has been made easier. Given this encouraging classification
      performance, the extension to automatic classification and updating of control
      models for use with neural prostheses will enable regular adjustments capable of
      compensating for neural changes.

PMID- 25570203
TI  - In vivo evaluation of a MUECoG array for chronic stimulation.
AB  - Advancements in neural interfaces capable of neural stimulation have shown that
      neural implants may potentially target the central nervous system to treat
      neurological disorders. Unfortunately, many of the current technologies used to
      stimulate and record from the brain do not suffice for this purpose; those that
      provide a sufficient channel density, which is required for interfacing and
      chronic functionality in vivo, fail quickly, while others that last for an
      extended period of time in vivo are limited in recording and stimulation
      capabilities. Of the current methodologies available, electrocorticography (ECoG)
      based implants show promise for providing both high channel density interfaces as
      well as chronic functionality after implantation. This study evaluates the
      performance of a MUECoG for the purpose of chronic stimulation. 

PMID- 25570205
TI  - An intelligent wheelchair based on automated navigation and BCI techniques.
AB  - In this paper, we propose an intelligent wheelchair system that relies on a brain
      computer interface (BCI) and automatic navigation. When in operation, candidate
      destinations and waypoints are automatically generated on the basis of the
      current environment. Then, the user selects a destination using a P300-based BCI.
      Finally, the navigation system plans a path and navigates the wheelchair to the
      determined destination. While the wheelchair is in motion, the user can issue a
      stop command with the BCI. Using our system, the mental burden of the user can be
      alleviated to a large degree. Furthermore, our system can adapt to changes in the
      environment. The experimental results demonstrated the effectiveness of our
      system.

PMID- 25570206
TI  - Predicting hand orientation in reach-to-grasp tasks using neural activities from
      primary motor cortex.
AB  - Hand orientation is an important control parameter during reach-to-grasp task. In
      this paper, we presented a study for predicting hand orientation of non-human
      primate by decoding neural activities from primary motor cortex (M1). A non-human
      primate subject was guided to do reaching and grasping tasks meanwhile neural
      activities were acquired by chronically implanted microelectrode arrays. A
      Support Vector Machines (SVMs) classifier has been trained for predicting three
      different hand orientations using these M1 neural activities. Different number of
      neurons were selected and analyzed; the classifying accuracy was 94.1% with 2
      neurons and was 100% with 8 neurons. Data from highly event related neuron units
      contribute a lot to the accuracy of hand orientation prediction. These results
      indicate that three different hand orientations can be predicted accurately and
      effectively before the actual movements occurring with a small number of related
      neurons in M1.

PMID- 25570204
TI  - Local field potentials mitigate decline in motor decoding performance caused by
      loss of spiking units.
AB  - The technology underlying brain computer interfaces has recently undergone rapid
      development, though a variety of issues remain that are currently preventing it
      from becoming a viable clinical assistive tool. Though decoding of motor output
      has been shown to be particularly effective when using spikes, these decoders
      tend to degrade with the loss of subsets of these signals. One potential solution
      to this problem is to include features derived from LFP signals in the decoder to
      mitigate these negative effects. We explored this solution and found that the
      decline in decoding performance that accompanies spiking unit dropout was
      significantly reduced when LFP power features were included in the decoder.
      Additionally, high frequency LFP features in the 100-170 Hz band were more
      effective than low frequency LFP features in the 2-4 Hz band at protecting the
      decoder from a dropoff in performance. LFP power appears to be an effective
      signal to improve the robustness of spiking unit decoders. Future studies will
      explore online classification and performance improvements in chronic implants by
      the proposed method.

PMID- 25570207
TI  - Discriminative channel addition and reduction for filter bank common spatial
      pattern in motor imagery BCI.
AB  - An electroencephalography (EEG)-based Motor Imagery Brain-Computer Interface (MI
      BCI) requires a long setup time if a large number of channels is used, and EEG
      from noisy or irrelevant channels may adversely affect the classification
      performance. To address this issue, this paper proposed 2 approaches to
      systematically select discriminative channels for EEG-based MI-BCI. The proposed
      Discriminative Channel Addition (DCA) approach and the Discriminative Channel
      Reduction (DCR) approach selects subject-specific discriminative channels by
      iteratively adding or removing channels based on the cross-validation
      classification accuracies obtained using the Filter Bank Common Spatial Pattern
      algorithm. The performances of the proposed approaches were evaluated on the BCI
      Competition IV Dataset 2a. The results on 2-class and 4-class MI data showed that
      DCA, which iteratively adds channels, selected 13~14 channels that consistently
      yielded better cross-validation accuracies on the training data and session-to
      session transfer accuracies on the evaluation data compared to the use of a full
      22-channel setup. Hence, this results in a reduced channel setup that could
      improve the classification accuracy of the MI-BCI after removing less
      discriminative channels.

PMID- 25570208
TI  - Discriminating hand gesture motor imagery tasks using cortical current density
      estimation.
AB  - Current EEG based brain computer interface (BCI) systems have achieved successful
      control in up to 3 dimensions; however the current paradigm may be unnatural for
      many rehabilitative and recreational applications. Therefore there is a great
      need to find motor imagination (MI) tasks that are realistic for output device
      control. In this paper we present our results on classifying hand gesture MI
      tasks, including right hand flexion, extension, supination and pronation using a
      novel EEG inverse imaging approach. By using both temporal and spatial
      specificity in the source domain we were able to separate MI tasks with up to 95%
      accuracy for binary classification of any two tasks compared to a maximum of only
      79% in the sensor domain.

PMID- 25570209
TI  - Decoding of attentional selection in a cocktail party environment from single
      trial EEG is robust to task.
AB  - Recently it has been shown to be possible to ascertain the target of a subject's
      attention in a cocktail party environment from single-trial (~60 s)
      electroencephalography (EEG) data. Specifically, this was shown in the context of
      a dichotic listening paradigm where subjects were cued to attend to a story in
      one ear while ignoring a different story in the other and were required to answer
      questions on both stories. This paradigm resulted in a high decoding accuracy
      that correlated with task performance across subjects. Here, we extend this
      finding by showing that the ability to accurately decode attentional selection in
      a dichotic speech paradigm is robust to the particular attention task at hand.
      Subjects attended to one of two dichotically presented stories under four task
      conditions. These conditions required subjects to 1) answer questions on the
      content of both stories, 2) detect irregular frequency fluctuations in the voice
      of the attended speaker 3) answer questions on both stories and detect frequency
      fluctuations in the attended story, and 4) detect target words in the attended
      story. All four tasks led to high decoding accuracy (~89%). These results offer
      new possibilities for creating user-friendly brain computer interfaces (BCIs).

PMID- 25570210
TI  - Enhancing accuracy of mental fatigue classification using advanced computational
      intelligence in an electroencephalography system.
AB  - A system using electroencephalography (EEG) signals could enhance the detection
      of mental fatigue while driving a vehicle. This paper examines the classification
      between fatigue and alert states using an autoregressive (AR) model-based power
      spectral density (PSD) as the features extraction method and fuzzy particle swarm
      optimization with cross mutated of artificial neural network (FPSOCM-ANN) as the
      classification method. Using 32-EEG channels, results indicated an improved
      overall specificity from 76.99% to 82.02%, an improved sensitivity from 74.92 to
      78.99% and an improved accuracy from 75.95% to 80.51% when compared to previous
      studies. The classification using fewer EEG channels, with eleven frontal sites
      resulted in 77.52% for specificity, 73.78% for sensitivity and 75.65% accuracy
      being achieved. For ergonomic reasons, the configuration with fewer EEG channels
      will enhance capacity to monitor fatigue as there is less set-up time required. 

PMID- 25570211
TI  - Towards a gaze-independent hybrid-BCI based on SSVEPs, alpha-band modulations and
      the P300.
AB  - In recent years it has been shown to be possible to create a Brain Computer
      Interface (BCI) using non-invasive electroencephalographic (EEG) measurements of
      covert visual spatial attention. For example, that both Steady-State Visual
      Evoked Potentials (SSVEP) and parieto-occipital alpha band activity have been
      shown to be sensitive to covert attention and this has been exploited to provide
      simple communication control without the need for any physical movement. In this
      study, potential improvements in the speed and accuracy of such a BCI are
      investigated by exploring the possibility of incorporating a P300 task into an
      SSVEP covert attention paradigm. Should this be possible it would pave the way
      for a gaze-independent hybrid BCI based on three somewhat independent EEG
      signals. Within a well-established SSVEP-based attention paradigm we show that it
      is possible to make a binary classification of covert attention using just the
      P300 with an average accuracy of 71% across three subjects. We also validate
      previously published research by showing robust attention effects on the SSVEP
      and alpha band activity within this paradigm. In future work, it is hoped that by
      integrating the three signals into a hybrid BCI a significant improvement in
      performance will be forthcoming leading to an easily usable real time
      communication device for patients with severe disabilities such as Locked-In
      Syndrome (LIS).

PMID- 25570212
TI  - Temporal changes of beta rhythms and rotation-related negativity reflect switches
      in motor imagery.
AB  - While motor imagery has been known as a powerful tool for neuro-rehabilitation in
      stroke patients, whether this technique is also effective for other brain
      disorders is unclear. For instance, patients with Parkinson's disease or
      attention-deficit hyperactivity disorder who are impaired at real motor switching
      may benefit therapeutically from training that consists of switching their
      imagined motor movements, and eventually recover from the dysfunction. However,
      despite its importance little is known about exactly how switching mental images
      of one's actions is processed in the brain. Therefore, we set out to clarify this
      issue by measuring brain activity reflected in electroencephalograms as subjects
      switched an imagined hand rotation from one hand to the other during a motor
      imagery task. By comparing electroencephalogram signals from repeated mental
      imaging of hand movements, we found a switch-specific decrease in the beta-band
      activity in parietal and frontal regions around 0.6 s after stimulus
      presentation. Further, we found rotation-related negativity in the parietal
      cortex at the same time as the decreased beta-band power. These results suggest
      that the parietal area is dynamically involved in the switching of imagined hand
      motion, and that frontal areas may have an important role in inhibiting mental
      imagery of the deselected hand's motion.

PMID- 25570213
TI  - Towards an enhanced ERP speller based on the visual processing of face
      familiarity.
AB  - In this study, a novel P300 based brain-computer interface (BCI) system using
      random set presentation pattern and employing the effect of face familiarity has
      been proposed and developed. While the effect of face familiarity is widely
      studied in the cognitive neurosciences, it has so far not been addressed for the
      purpose of BCI. We compare P300-based BCI performances of a conventional row
      column (RC)-based paradigm with our novel approach. Our experimental results
      indicate stronger deflections of the ERPs in response to face stimuli and thereby
      improving P300-based spelling performance. This leads to a significant reduction
      of stimulus sequences required for correct character classification. These
      findings demonstrate a promising new approach for improving the speed and thus
      fluency of BCI-enhanced communication with the widely used P300-based BCI setup.

PMID- 25570214
TI  - Differences in motor cortical representations of kinematic variables between
      action observation and action execution and implications for brain-machine
      interfaces.
AB  - Observing an action being performed and executing the same action cause similar
      patterns of neural activity to emerge in the primary motor cortex (MI). Previous
      work has shown that the neural activity evoked during action observation (AO) is
      informative as to both the kinematics and muscle activation patterns of the
      action being performed, although the neural activity recorded during action
      observation contains less information than the activity recorded during action
      execution (AE). In this study, we extend these results by comparing the
      representation of different kinematic variables in MI single /multi unit activity
      between AO and AE conditions in three rhesus macaques. We show that the
      representation of acceleration decreases more significantly than that of position
      and velocity in AO (population decoding performance for acceleration decreases
      more steeply, and fewer neurons in AO encode acceleration significantly as
      compared to AE). We discuss the relevance of these results to brain-machine
      interfaces that make use of neural activity during AO to initialize a mapping
      function between neural activity and motor commands.

PMID- 25570215
TI  - Towards an architecture of a hybrid BCI based on SSVEP-BCI and passive-BCI.
AB  - Recent decades have seen BCI applications as a novel and promising new channel of
      communication, control and entertainment for disabled and healthy people.
      However, BCI technology can be prone to errors due to the basic emotional state
      of the user: the performance of reactive and active BCIs decrease when user
      becomes stressed or bored, for example. Passive-BCI is a recent approach that
      fuses BCI technology with cognitive monitoring, providing valuable information
      about the user's intentions, the situational interpretations and mainly the
      emotional state. In this work, an architecture composed by passive-BCI co-working
      with SSVEP-BCI is proposed, with the aim of improving the performance of the
      reactive-BCI. The possibility of adjusting recognition characteristics of SSVEP
      BCIs using a passive-BCI output is evaluated. In this sense, two ways to recover
      the accuracy of SSVEP are presented in this paper: 1) Adjusting of Amplitude of
      the SSVEP and 2) Adjusting of Frequency of the SSVEP response. The results are
      promising, because accuracy of SSVEP-BCI can be recovered in the case that it was
      reduced by the BCI user's emotional state.

PMID- 25570216
TI  - An empiric weight computation for record linkage using linearly combined fields'
      similarity scores.
AB  - Record linkage is the task of identifying which records from one or more data
      sources refer to the same entity. Many record linkage methods were introduced and
      applied over the last decades. In general, the principle is to compare a range of
      available identifier fields in record pairs among different data sources, in
      order to make a linkage decision. The Fellegi-Sunter probabilistic record linkage
      (PRL-FS) is one of the most commonly used methods. To obtain a better
      performance, Winkler proposed an enhanced PRL-FS method (PRL-W) that takes into
      account field similarity, but its implementation requires the estimation of much
      more parameters which complicates the task. Consequently, we propose to develop a
      method that contains the best features in the PRL-FS and the PRL-W methods:
      simplicity of parameters estimation and consideration of fields' similarities. We
      hypothesize that our record linkage method outperforms the PRL-FS, and can
      achieve a similar performance of the PRL-W. This paper presents briefly the PRL
      FS and PRL-W methods, and describes in details how to combine fields' similarity
      scores to create a novel record pair weight. Simulated data sets were used to
      assess and to compare these three methods regarding their ability to reduce the
      rates of false matches and false non-matches.

PMID- 25570217
TI  - Comparative performance investigation of DICOM C-STORE and DICOM HTTP-based
      requests.
AB  - Increasingly, physicians have to access clinical images distributed over multiple
      healthcare organizations. To this end, two DICOM protocols may be used: a regular
      DICOM C-STORE transaction or an HTTP-based DICOM request such as WADO or STOW. A
      major problem of the DICOM C-STORE transaction is that it is inefficient to
      transfer DICOM data sets that consist of thousands of DICOM objects (such as
      functional MRI data set) because of the large number of negotiations involved in
      the transfer. We compare the performances of C-STORE transactions with the STOW
      HTTP-based protocol, and show that the STOW protocol can divide the transfer time
      by about 50 when compared to a DICOM C-STORE transaction for studies that
      consists of thousands of DICOM objects.

PMID- 25570218
TI  - Electronic health records for cardiovascular medicine.
AB  - Nowadays, many cardiology health care centers and hospitals adopt new
      technologies to improve interaction with their patients. The Electronic Health
      Records (EHR) offer health care centers and institutions the possibility to
      improve the management of their patients' health data. Currently, many physicians
      are using EHRs to improve health care quality and efficiency. A large number of
      companies have emerged to provide hospitals with the opportunity to adopt EHRs
      within a health care platform proposing different functionalities and services
      which achieve certain certification criteria. This paper identifies the current
      list of certified EHRs for cardiovascular medicine and assesses the
      specifications of the EHRs selected. The result of this paper may assist EHR
      seekers for cardiovascular medicine in their tasks.

PMID- 25570219
TI  - The study on a real-time remote monitoring system for Parkinson's disease
      patients with deep brain stimulators.
AB  - The Deep Brain Stimulation (DBS) has become a well-accepted treatment for
      Parkinson's disease patients around the world. However, postoperative care of the
      stimulators usually puts a heavy burden on the patients' families, especially in
      China. To solve the problem, this study developed a real-time remote monitoring
      system for deep brain stimulators. Based on Internet technologies, the system
      offers remote adjustment service so that in vivo stimulators could be programmed
      at patients' home by clinic caregivers. We tested the system on an experimental
      condition and the results have proved that this early exploration of remote
      monitoring deep brain stimulators was successful.

PMID- 25570220
TI  - Healthcare information exchange system based on a hybrid central/federated model.
AB  - The quality of care can be significantly enhanced and healthcare cost can be
      substantially reduced if healthcare providers can have access to patient records
      that are scattered among several paper and electronic based systems. Major
      challenges of Healthcare Information Exchange result from patient's medical
      records being kept in several healthcare provider offices, clinics and hospitals
      in different formats. There are two major problems with healthcare information
      retrieval. The first problem is lack of visibility and knowledge as to where
      patient's medical records reside. The second problem is lack of access to
      information and also incompatibility of data formats. A considerable coverage of
      Electronic Information Exchange among Electronic Health Record (EHR) systems
      remains to be implemented despite extensive standardization efforts toward
      providing solutions. The adoption pace of available standards and solutions has
      been slow with the exception of some public/government entities. This paper
      describes a comprehensive and practical solution based on a distributed system
      with independent subsystems that control and manage processes and data flow of
      information exchange. The Registrar Subsystem creates a directory of healthcare
      providers and patients. The Security Subsystem provides authentication and
      authorization services across all subsystems. The Locators address patient and
      medical location lookup. The Agents act on behalf of healthcare providers to
      communicate with other subsystems. The Mediators facilitate information
      retrieval. The Solution comprises of three levels of participation that allows
      healthcare providers to join the system easily by starting from basic semi-manual
      information exchange level and then migrating to a fully electronic and automated
      information exchange. The Solution is modeled based on variety of standards and
      protocols used in Internet and other application fields as well as healthcare
      specific standards and proposals.

PMID- 25570222
TI  - Home area network for optimizing telehealth services--empirical simulation
      analysis.
AB  - Telehealth applications such as Video-over-IP and remote sensor monitoring are
      rapidly growing in utilisation and it has now expanded to the patient's homes.
      These Telehealth applications are, however highly delay sensitive and require
      high quality (and bandwidth priority) in order to provide satisfactory
      performances. However, at the patient's home area network (HAN) environment,
      typically there is no Internet traffic management system which highly affects the
      quality of these applications. As HAN expands its capacity by adding new devices
      in its network, the need for a network management system become urgent and
      necessary. In this study, we propose an infrastructure based method to improve
      Telehealth application quality by managing the quality and distribution of the
      Internet traffic among the connected devices in a HAN environment. We setup a HAN
      environment using existing devices readily available at home and tested the
      setting with typical Telehealth application needs that includes Video-over-IP,
      VoIP, data and other multimedia traffic. Our simulation results showed that our
      method is capable of providing better services. Our method indicated that it can
      provide ~11% lesser packet-loss under 12Mbps background traffic, while increasing
      10% of the CPU load for Traffic management.

PMID- 25570221
TI  - Design of an interactive medical guideline application for community health
      workers.
AB  - Clinical guidelines, such as the Integrated Management of Childhood Illness
      (IMCI), are used worldwide to support community health workers in the assessment
      of severely ill children. These guidelines are distributed in paper form,
      complicating their use at the point-of-care. We have developed a framework for
      building advanced clinical guideline applications for the Android mobile phone
      OS. The framework transfers clinical guidelines into a flexible and interactive
      electronic format using an XML interpreter. The resulting application supports
      intuitive navigation of guidelines while assessing the patient, easy integration
      of patient management tools, and logging of performed assessments and treatments.
      The novel approach transforms clinical guidelines from a mere paper dictionary
      into a working tool that integrates into the daily workflow of community health
      workers and simplifies their task at the care and administrative levels.

PMID- 25570223
TI  - Interoperability of wearable cuffless BP measuring devices.
AB  - While a traditional cuff-based Blood Pressure (BP) measuring device can only take
      a snap shot of BP, real-time and continuous measurement of BP without an
      occluding cuff is preferred which usually use the pulse transit time (PTT) in
      combination with other physiological parameters to estimate or track BP over a
      certain period of time after an initial calibration. This article discusses some
      perspectives of interoperability of wearable medical devices, based on IEEE P1708
      draft standard that focuses on the objective performance evaluation of wearable
      cuffless BP measuring devices. The ISO/IEEE 11073 family of standards, supporting
      the plug-and play feature, is intended to enable medical devices to interconnect
      and interoperate with other medical devices and with computerized healthcare
      information systems in a manner suitable for the clinical environment. In this
      paper, the possible adoption of ISO/IEEE 11073 for the interoperability of
      wearable cuffless BP devices is proposed. In the consideration of the difference
      of the continuous and cuffless BP measuring methods from the conventional ones,
      the existing device specialization standards of ISO/IEEE 11073 cannot be directly
      followed when designing the cuffless BP device. Specifically, this paper
      discusses how the domain information model (DIM), in which vital sign information
      is abstracted as objects, is used to structure the information about the device
      and that generated from the device. Though attention should also be paid to adopt
      the communication standards for other parts for the communication system,
      applying communication standards that enable plug-and-play feature allows
      achieving the interoperability of different cuffless BP measuring devices with
      possible different configurations.

PMID- 25570224
TI  - A teledentistry system for the second opinion.
AB  - In this paper we present a Teledentistry system aimed to the Second Opinion task.
      It make use of a particular camera called intra-oral camera, also called dental
      camera, in order to perform the photo shooting and real-time video of the inner
      part of the mouth. The pictures acquired by the Operator with such a device are
      sent to the Oral Medicine Expert (OME) by means of a current File Transfer
      Protocol (FTP) service and the real-time video is channeled into a video
      streaming thanks to the VideoLan client/server (VLC) application. It is composed
      by a HTML5 web-pages generated by PHP and allows to perform the Second Opinion
      both when Operator and OME are logged and when one of them is offline. 

PMID- 25570225
TI  - Remote, real-time monitoring and analysis of vital signs of neonatal graduate
      infants.
AB  - This paper presents a system for the remote monitoring of a newborn infant's
      physiological data outside the Neonatal Intensive Care Unit. By providing a
      simple means for parents to enable monitoring, and physicians a simple mobile
      application to monitor live and historical physiological information, this system
      provides the insight once only possible in an Intensive Care Unit. The system
      utilizes a variety of connectivity means such as Wi-Fi and 3G to facilitate the
      communication between a multitude of industry standard vital sign monitor and a
      remote server. A system trial monitoring an infant to simulate neonatal graduate
      monitoring has determined the system was able to successfully transmit 99.99% of
      data generated from the vital sign monitor.

PMID- 25570226
TI  - An interoperable pillbox system for smart medication adherence.
AB  - We have designed and fabricated an interoperable system for medication adherence.
      The system is composed of a pillbox that wirelessly communicates with a computer
      application and a custom-made wristband. The system receives the information of
      taking specific medication from the user or caregiver, reminds the user to take
      the medication, monitors the user's hand gesture during the medication intake and
      monitors the compartments of the pillbox for refilling purpose. The performance
      of the developed system was examined in various bench-top scenarios. The system
      has the potential to improve the existing systems by reminding the user to take
      the medication through the wristband, automatically collecting user's hand
      gestures during the medication intake, and providing detailed information about
      the exisexistencetence of medication in the compartments of the pillbox.

PMID- 25570227
TI  - Magnetically guided micro-droplet using biological magnetic material for smart
      drug delivery system.
AB  - Biodegradable polymer droplet containing magnetosome demonstrates active
      propulsion by magnetic field. Magnetosome is extracted from magnetotactic
      bacteria, AMB-1. Mixture of magnetosome and sodium alginate composes into droplet
      using the microfluidic device applied Plateau-Rayleigh instability principle. The
      magnetosome-contained droplet selects its route at the bifurcate microchannels by
      magnetic field. This shows tissue targeting potential of the proposed drug
      delivery system.

PMID- 25570228
TI  - Geometric decoupling of a mouse array coil using a dual plane pair design with
      crisscrossed return paths and custom mounting fixture.
AB  - An element design for receive array coils that decouples from the transmit coil
      without external active detuning is presented for magnetic resonance imaging
      (MRI) of mice. The array element uses a crisscrossed geometry on the return paths
      to reduce the current induced by the transmit coil. Without the need for an
      external active detune network, the proposed method simplifies the construction
      of MRI coil systems and also mitigates problems in space-limited MRI
      applications. In addition, an adaptable scissor-jack-like fixture is presented
      that allows the receive array to move parallel to the transmit coil to maintain
      the decoupling condition while maintaining close contact with varying sizes of
      mice. 

PMID- 25570229
TI  - A low pull-in SU-8 based Capacitive Micromachined Ultrasonic Transducer for
      medical imaging applications.
AB  - In this paper we present a thorough analysis of a low pull-in voltage Capacitive
      Micromachined Ultrasonic Transducer (CMUT) using SU-8 as the membrane material.
      It is designed to operate at 1 MHz frequency that has a wide range of
      applications including the imaging of deeper organs. We also propose a simple
      state-of-the-art fabrication methodology for the same. As compared to the
      standard Silicon Nitride CMUTs, the proposed structure gives the same
      electromechanical coupling coefficient with lower membrane dimensions and low
      pull-in voltage which in turn results in reduced area and power consumption.
      Moreover the proposed fabrication methodology is a low temperature process which
      makes it CMOS compatible.

PMID- 25570230
TI  - Dielectrophoresis-based classification of cells using multi-target multiple
      hypothesis tracking.
AB  - In this paper we present a novel methodology for classifying cells by using a
      combination of dielectrophoresis, image tracking and classification algorithms.
      We use dielectrophoresis to induce unique motion patterns in cells of interest.
      Motion is extracted via multi-target multiple-hypothesis tracking. Trajectories
      are then used to classify cells based on a generalized likelihood ratio test. We
      present results of a simulation study and of our prototype tracking the
      dielectrophoretic velocities of cells. 

PMID- 25570231
TI  - Modeling the magnetic disturbance of pulsatile blood flow in a static magnetic
      field.
AB  - Non-invasive continuous monitoring of blood flow may be particularly valuable for
      early detection of different anomalies such as hypovolemia and internal bleeding.
      Recent studies have demonstrated the potential clinical benefits of photo
      plethysmography in detecting hypovolemia before the onset of cardiovascular
      decompensation. The magnetic sensing method bears advantages of size, weight, and
      cost along with less stringent body placement rules. In this work, a detailed
      three-dimensional mathematical model for the acquisition of the ventricular
      response using the disturbance created by magnetized blood undergoing a
      stationary permanent magnet is presented. The proposed model accounts for the
      different magnetic properties of the blood such as the relaxation time and the
      magnetic saturation. The blood flow is simulated by means of Navier-Stocks
      equations with pulsatile inlet pressure. The blood is assumed to be in the
      deoxygenated state and has a diamagnetic properties. Moreover, a moving mesh
      technique is implemented in the Finite-Element model to represent the idle and
      the moving states of the blood which provides the capability to model the
      magnetized blood as a moving magnet. The simulated magnetic field at different
      sensor locations is found to be in good agreement with experimental observations
      from the literature. The presented model can provide basis for understanding the
      magnetic modulated blood signal as well as the practical constraints that might
      be encountered in the design of such devices. 

PMID- 25570232
TI  - Tongue-Supported Human-Computer Interaction systems: a review.
AB  - The tongue can substitute human sensory systems and has been used as a medium of
      input to help impaired patients communicate with the world. Innovative techniques
      have been employed to realize tongue movement, sense its position and exploit
      tongue dexterity, in order to achieve Tongue Supported Human Computer Interaction
      (TSHCI). This paper examines various approaches of using tongue dexterousness in
      TSHCI systems and introduces two infrared signal supported minimally-invasive
      TSHCI systems developed at Curtin University. Methods of sensing tongue movement
      and position are especially discussed and depending on the employed methods,
      TSHCI systems are categorized as either invasive or minimally-invasive. A set of
      system usability criteria is proposed to help build more effective TSHCI systems
      in future.

PMID- 25570233
TI  - Development of a miniaturized bioreactor for neural culture and axon stretch
      growth.
AB  - In this paper, a miniaturized bioreactor for accelerating nerve growth is
      developed to investigate potentially bi-directional peripheral neural interface
      based on tissue engineering. The bioreactor consisting of two parallel chambers
      that are extended to conduct controlled trials for optimized neuronal culture.
      The chamber is used to improve the micro-environment of in vitro nerve
      regeneration in a CO2 incubator, whereas the process of axon stretch growth is
      performed by a computer controlled micro-motion system comprised of a linear
      motion table and a micro-stepper motor. This apparatus produces axon stretch
      growth by taking l MUm step every 1 minute over 1000 iterations for 1mm
      elongation growth per day. Results show that axons from neonatal DRG explants are
      grown with unidirectional polarity with a robust regeneration over 5 days in the
      culture chamber, whereas micro-displacement measurement indicates a satisfactory
      accuracy and repeatability for the implementation of computer-controlled ASG.

PMID- 25570234
TI  - A frequency-sensing readout using piezoelectric sensors for sensing of
      physiological signals.
AB  - Together with a charge or voltage amplifier, piezoelectric sensors are commonly
      used to pick up physiological vibrations from the body. As an alternative to
      chopper or auto-zero amplifiers, frequency sensing is known in literature to
      provide advantages of noise immunity, interfacing to digital readout systems as
      well as tunable range of sensing. A frequency-sensing readout circuit for sensing
      low voltage signals from piezoelectric sensors is successfully developed and
      tested in this work. The output voltage of a piezoelectric sensor is fed to a
      varactor, which is part of an Colpitts LC oscillator. The oscillation frequency
      is converted into a voltage using a phase locked loop. The circuit is compared to
      a reference design in terms of linearity, noise and transfer function. The
      readout has a input-referred noise voltage of 2.24MUV/?Hz and consumes 15 mA at
      5V supply. Arterial pulse wave signals and the cardiac vibrations from the chest
      are measured from one subject to show the proof of concept of the proposed
      readout. The results of this work are intended to contribute towards alternative
      low noise analog front end designs for piezoelectric sensors.

PMID- 25570235
TI  - Investigation of electrical stimulus on chitosan film based DDS.
AB  - Controlled drug release is crucial for targeted implant smart drug delivery
      system (DDS). In this work a chitosan film loaded with green food coloring is
      fabricated to demonstrate the concepts of drug release using electrical stimulus.
      A simulation model is also developed to explain the physical phenomena of this
      drug release using finite element method (FEM). It is found that drug delivery is
      increased with applied electric field to the electrodes on chitosan film. The AC
      electrokinetic force generated from electrical excitation is a factor influencing
      this phenomenon. Several controlled and stimuli experiments are conducted with
      different electric fields and frequencies. The spectral absorbance of treated
      solution after the experiment is measured using a spectrophotometer to quantify
      the dye release. It is verified statistically with 99% level of significance that
      the amount of dye release has increased with applied electric field. Thus this
      work has shown that application of electric field can be a potential candidate
      for controlled DDS using chitosan film.

PMID- 25570236
TI  - Tissue strands as "bioink" for scale-up organ printing.
AB  - Organ printing, takes tissue spheroids as building blocks together with additive
      manufacturing technique to engineer tissue or organ replacement parts. Although a
      wide array of cell aggregation techniques has been investigated, and gained
      noticeable success, the application of tissue spheroids for scale-up tissue
      fabrication is still worth investigation. In this paper, we introduce a new micro
      fabrication technique to create tissue strands at the scale of 500-700MUm as a
      "bioink" for future robotic tissue printing. Printable alginate micro-conduits
      are used as semi-permeable capsules for tissue strand fabrication. Mouse
      insulinoma beta TC3 cell tissue strands were formed upon 4 days post fabrication
      with reasonable mechanical strength, high cell viability close to 90%, and tissue
      specific markers expression. Fusion was readily observed between strands when
      placing them together as early as 24h. Also, tissue strands were deposited with
      human umbilical vein smooth muscle cells (HUVSMCs) vascular conduits together to
      fabricated miniature pancreatic tissue analog. Our study provided a novel
      technique using tissue strands as "bioink" for scale-up bioprinting of tissues or
      organs.

PMID- 25570237
TI  - Phantom materials mimicking the optical properties in the near infrared range for
      non-invasive fetal pulse oximetry.
AB  - An optical phantom of the maternal abdomen during pregnancy is an appropriate
      test environment to evaluate a non-invasive system for fetal pulse oximetry. To
      recreate the optical properties of maternal tissue, fetal tissue and blood
      suitable substitutes are required. For this purpose, phantom materials are used,
      which consist of transparent silicone or water as host material. Cosmetic powder
      and India ink are investigated as absorbing materials, whereas titanium dioxide
      particles are examined as scattering medium. Transmittance and reflectance
      measurements of the samples were performed in the spectral range from 600 nm to
      900 nm using integrating sphere technique. The scattering and absorption
      coefficients and the anisotropy factor were determined using Kubelka-Munk theory.
      The results were used to compute the required mixture ratios of the respective
      components to replicate the optical properties of maternal tissue, fetal tissue
      and blood, and corresponding samples were produced. Their optical properties were
      investigated in the same manner as mentioned above. The results conform to the
      values of various types of tissues and blood given in the scientific literature.

PMID- 25570238
TI  - Tracheal activity recognition based on acoustic signals.
AB  - Tracheal activity recognition can play an important role in continuous health
      monitoring for wearable systems and facilitate the advancement of personalized
      healthcare. Neck-worn systems provide access to a unique set of health-related
      data that other wearable devices simply cannot obtain. Activities including
      breathing, chewing, clearing the throat, coughing, swallowing, speech and even
      heartbeat can be recorded from around the neck. In this paper, we explore
      tracheal activity recognition using a combination of promising acoustic features
      from related work and apply simplistic classifiers including K-NN and Naive
      Bayes. For wearable systems in which low power consumption is of primary concern,
      we show that with a sub-optimal sampling rate of 16 kHz, we have achieved average
      classification results in the range of 86.6% to 87.4% using 1-NN, 3-NN, 5-NN and
      Naive Bayes. All classifiers obtained the highest recognition rate in the range
      of 97.2% to 99.4% for speech classification. This is promising to mitigate
      privacy concerns associated with wearable systems interfering with the user's
      conversations.

PMID- 25570239
TI  - Hardware-efficient robust biometric identification from 0.58 second template and
      12 features of limb (Lead I) ECG signal using logistic regression classifier.
AB  - The electrocardiogram (ECG), widely known as a cardiac diagnostic signal, has
      recently been proposed for biometric identification of individuals; however
      reliability and reproducibility are of research interest. In this paper, we
      propose a template matching technique with 12 features using logistic regression
      classifier that achieved high reliability and identification accuracy. Non
      invasive ECG signals were captured using our custom-built ambulatory EEG/ECG
      embedded device (NeuroMonitor). ECG data were collected from healthy subjects
      (10), between 25-35 years, for 10 seconds per trial. The number of trials from
      each subject was 10. From each trial, only 0.58 seconds of Lead I ECG data were
      used as template. Hardware-efficient fiducial point detection technique was
      implemented for feature extraction. To obtain repeated random sub-sampling
      validation, data were randomly separated into training and testing sets at a
      ratio of 80:20. Test data were used to find the classification accuracy. ECG
      template data with 12 extracted features provided the best performance in terms
      of accuracy (up to 100%) and processing complexity (computation time of 1.2ms).
      This work shows that a single limb (Lead I) ECG can robustly identify an
      individual quickly and reliably with minimal contact and data processing using
      the proposed algorithm.

PMID- 25570240
TI  - On computation of calcium cycling anomalies in cardiomyocytes data.
AB  - Induced pluripotent stem cell (iPSC) lines derived from skin fibroblasts of
      patients suffering from cardiac disorders were differentiated to cardiomyocytes
      and used to generate a data set of Ca(2+) transients of 136 recordings. The
      objective was to separate normal signals for later medical research from abnormal
      signals. We constructed a signal analysis procedure to detect peaks representing
      calcium cycling in signals and another procedure to classify them into either
      normal or abnormal peaks. Using machine learning methods we classified signals
      into normal or abnormal signals on the basis of peak findings in them. We
      compared classification results obtained to those made visually by an expert
      biotechnologist who assessed the signals independent of the computer method.
      Classification accuracies of around 85% indicated high congruence between two
      modes denoting the high capability and usefulness of computer based processing
      for the present data.

PMID- 25570241
TI  - Real-time arrhythmia classification for large databases.
AB  - In this paper we introduce a coarse-to-fine arrhythmia classification technique
      that can be used for efficient processing of large Electrocardiogram (ECG)
      records. This technique reduces time-complexity of arrhythmia classification by
      reducing size of the beats as well as by quantizing the number of beats using
      Multi-Section Vector Quantization (MSVQ) without compromising on the accuracy of
      the classification. The proposed solution is tested on MIT-BIH arrhythmia
      database. This work achieves a highest computational speed-up factor of 2.2:1 in
      comparison with standard arrhythmia classification technique with marginal loss
      (<;1%) in classification accuracy. The clinical application of this technique
      enhances physician's throughput by factor of 2x while processing large ECG
      records from Holter system. 

PMID- 25570242
TI  - Fetal movement detection based on QRS amplitude variations in abdominal ECG
      recordings.
AB  - Evaluation of fetal motility can give insight in fetal health, as a strong
      decrease can be seen as a precursor to fetal death. Typically, the assessment of
      fetal health by fetal movement detection relies on the maternal perception of
      fetal activity. The percentage of detected movements is strongly subject
      dependent and with undivided attention of the mother varies between 37% to 88%.
      Various methods to assist in fetal movement detection exist based on a wide
      spectrum of measurement techniques. However, these are typically unsuitable for
      ambulatory or long-term observation. In this paper, a novel method for fetal
      motion detection is presented based on amplitude and shape changes in the
      abdominally recorded fetal ECG. The proposed method has a sensitivity and
      specificity of 0.67 and 0.90, respectively, outperforming alternative fetal ECG
      based methods from the literature.

PMID- 25570243
TI  - Computation of resting state networks from fMRI through a measure of phase
      synchrony.
AB  - Resting-state fMRI (rs-fMRI) studies of the human brain have demonstrated that
      low-frequency fluctuations can define functionally relevant resting state
      networks (RSNs). The majority of these methods rely on Pearson's correlation for
      quantifying the functional connectivity between the time series from different
      regions. However, it is well-known that correlation is limited to quantifying
      only linear relationships between the time series and assumes stationarity of the
      underlying processes. Many empirical studies indicate nonstationarity of the BOLD
      signals. In this paper, we adapt a measure of time-varying phase synchrony to
      quantify the functional connectivity and modify it to distinguish between
      synchronization and desynchronization. The proposed measure is compared to the
      conventional Pearson's correlation method for rs-fMRI analyses on two subjects
      (six scans per subject) in terms of their reproducibility.

PMID- 25570244
TI  - Diagnosis of Ocular Myasthenia Gravis by means of tracking eye parameters.
AB  - Ptosis of the eyelids is a common condition with a myriad of causes. Its
      management depends on the underlying cause, which can be challenging to diagnose
      in some cases. Current diagnosis methods include serum antibodies, tensilon test,
      and electromyography (EMG). Each has its own set of limitations such as
      invasiveness and lack of sensitivity. To overcome these limitations, we have
      developed a Portable Realtime Infrared Lids, Iris and Blink (PRILIB) monitoring
      system, with a long-term goal to improve clinical diagnosis of ptosis. In this
      paper, we present the algorithms to detect and analyze eye parameters and report
      experimental results. From experiments conducted on normal volunteers and
      myasthenic patients, we found 1. Partial blinks happen when Ocular Myasthenia
      Gravis (OMG) patients are tired or engaged in an activity; 2. Blink rate is
      significantly higher for OMG patients due to failure to blink fully; 3. There are
      noticeably more fluctuations of palpebral aperture of OMG patients due to rising
      and falling of the eyelid height. These experimental findings suggest new
      diagnostic features for OMG patients and have implications for disease
      management. 

PMID- 25570245
TI  - Directional dual-tree rational-dilation complex wavelet transform.
AB  - Dyadic discrete wavelet transform (DWT) has been used successfully in processing
      signals having non-oscillatory transient behaviour. However, due to the low Q
      factor property of their wavelet atoms, the dyadic DWT is less effective in
      processing oscillatory signals such as embolic signals (ESs). ESs are extracted
      from quadrature Doppler signals, which are the output of Doppler ultrasound
      systems. In order to process ESs, firstly, a pre-processing operation known as
      phase filtering for obtaining directional signals from quadrature Doppler signals
      must be employed. Only then, wavelet based methods can be applied to these
      directional signals for further analysis. In this study, a directional dual-tree
      rational-dilation complex wavelet transform, which can be applied directly to
      quadrature signals and has the ability of extracting directional information
      during analysis, is introduced.

PMID- 25570246
TI  - Entropy-based multichannel measure of stationarity for characterization of motor
      imagery patterns.
AB  - We propose a novel approach for measuring the stationarity level of multichannel
      time-series. This measure is based on stationarity definition over time-varying
      spectra and aims to quantify the relationship between local (single-channel
      dynamics) and global (multichannel dynamics) stationarity. With the purpose of
      separate among several motor/imagery tasks, we asssume that movement imagination
      implies an increase on the EEG variability, consequently, as discriminant
      features, we first compute the non-stationary components of input signals, and we
      further obtain its stationary level throughout the proposed measure. To assess
      the separability level of the proposed features, we employ the t-student test.
      Obtained results evidence that our measure is able to accurately detect brain
      areas projected on the scalp where motor tasks are performed. 

PMID- 25570247
TI  - Robust features for detection of crackles: an exploratory study.
AB  - Crackles are adventitious and explosive respiratory sounds that can be classified
      as fine or coarse. These sounds are usually associated with cardiopulmonary
      diseases such as the chronic obstructive pulmonary disease. In this work seven
      different features were tested with the objective to identify the best subset of
      features that allows a robust detection of coarse crackles. Some of the features
      used in this study are new, namely those based on the local entropy, on the
      Teager energy and on the residual fit of a Generalized Autoregressive Conditional
      Heteroskedasticity process. The best features as a function of the number of
      features used in classification were identified having into account the Matthews
      correlation coefficient. The best individual feature was based on the local
      entropy. A significant improvement in the performance was obtained by using the
      feature based on local entropy and the feature based on the wavelet packed
      stationary transform - no stationary transform. The addition of more features
      only allows a smaller improvement.

PMID- 25570248
TI  - A quasi-local method for instantaneous frequency estimation with application to
      structural magnetic resonance images.
AB  - Spatially-varying signal content can be effectively modeled using amplitude
      modulation-frequency modulation (AM-FM) representations. The AM-FM representation
      allow us to extract instantaneous amplitude (IA) and instantaneous frequency (IF)
      components that can be used to measure non-stationary content in biomedical
      images and videos. This paper introduces a new method for estimating the IA and
      the IF based on a quasi-local method (QLM). We provide an extensive comparison of
      AM-FM demodulation approaches based on QLM and a quasi-eigenfunction
      approximation method using three different filter-banks: (i) a separable,
      equiripple design, (ii) a Gabor filter bank, and (iii) a directional filter bank
      approach based on the Contourlet transform. The results document that the use of
      the new QLM method with an equiripple filter bank design gave the best IF
      magnitude estimates for a synthetic image. The new QLM method is then applied to
      a multi-site schizophrenia dataset (N=307). The dataset included structure
      magnetic resonance images from healthy controls and patients diagnosed with
      schizophrenia. The IF magnitude is shown to be less sensitive to variations
      across sites as opposed to the standard use of SMRI images that suffered from
      significant dependency on the scanner configurations on different collection
      sites. Furthermore, the regions of interest identified through the use of the IF
      magnitude are in agreement with previous studies. 

PMID- 25570249
TI  - Simultaneous acquisition of high-rate early, middle, and late auditory evoked
      potentials.
AB  - Auditory evoked potentials (AEPs) are typically acquired at rates that facilitate
      their study as segregated by epochs relative to stimulus onset: early (ABR, 1.5
      15 ms), middle (MLR, 15-60 ms), and late (LAEP, >=60 ms) potentials. In
      particular, late AEPs are often acquired with stimulus repetition rates between
      0.1 Hz and 1 Hz, and are bandpass filtered to contain information only within 1
      30 Hz. These low repetition rates, filtering and low SNRs eliminate much of the
      potential contributions of the early and middle-latency responses in AEP
      recordings. This study aims to demonstrate a method for acquiring whole-AEP
      responses at higher stimulus repetition rates of 0.5 Hz to 10 Hz, by utilizing
      the Continuous Loop Averaging Deconvolution (CLAD) method, increasing the
      bandwidth of the recordings to 1-300 Hz to include early components, and using
      short-duration chirps to increase synchronous firing of the cochlear and auditory
      pathway neurons. Such a method may facilitate diagnostic or functional assessment
      of single AEP recordings for detection, identification, or evaluation of early,
      middle and late components of auditory responses. 

PMID- 25570250
TI  - Identification of the vestibulo-ocular reflex dynamics.
AB  - The vestibulo-ocular reflex (VOR) plays an important role in our daily activities
      by enabling us to fixate on objects during head movements. Modeling and
      identification of the VOR improves our insight into the system behavior and helps
      in diagnosing various disorders. However, the switching nature of eye movements,
      including the VOR, makes the dynamic analysis challenging. In this work we are
      using integration of subspace and prediction error methods to analyze VOR
      dynamics. The performance of the method is evaluated using simulation studies and
      experimental data.

PMID- 25570251
TI  - Detection of breathing sounds during sleep using non-contact audio recordings.
AB  - Evaluation of respiratory activity during sleep is essential in order to reliably
      diagnose sleep disorder breathing (SDB); a condition associated with serious
      cardio-vascular morbidity and mortality. In the current study, we developed and
      validated a robust automatic breathing-sounds (i.e. inspiratory and expiratory
      sounds) detection system of audio signals acquired during sleep. Random forest
      classifier was trained and tested using inspiratory/expiratory/noise events
      (episodes), acquired from 84 subjects consecutively and prospectively referred to
      SDB diagnosis in sleep laboratory and in at-home environment. More than 560,000
      events were analyzed, including a variety of recording devices and different
      environments. The system's overall accuracy rate is 88.8%, with accuracy rate of
      91.2% and 83.6% in in-laboratory and at-home environments respectively, when
      classifying between inspiratory, expiratory, and noise classes. Here, we provide
      evidence that breathing-sounds can be reliably detected using non-contact audio
      technology in at-home environment. The proposed approach may improve our
      understanding of respiratory activity during sleep. This in return, will improve
      early SDB diagnosis and treatment.

PMID- 25570252
TI  - Adaptive hybrid brain-computer interaction: ask a trainer for assistance!
AB  - In applying mental imagery brain-computer interfaces (BCIs) to end users,
      training is a key part for novice users to get control. In general learning
      situations, it is an established concept that a trainer assists a trainee to
      improve his/her aptitude in certain skills. In this work, we want to evaluate
      whether we can apply this concept in the context of event-related
      desynchronization (ERD) based, adaptive, hybrid BCIs. Hence, in a first session
      we merged the features of a high aptitude BCI user, a trainer, and a novice user,
      the trainee, in a closed-loop BCI feedback task and automatically adapted the
      classifier over time. In a second session the trainees operated the system
      unassisted. Twelve healthy participants ran through this protocol. Along with the
      trainer, the trainees achieved a very high overall peak accuracy of 95.3 %. In
      the second session, where users operated the BCI unassisted, they still achieved
      a high overall peak accuracy of 83.6%. Ten of twelve first time BCI users
      successfully achieved significantly better than chance accuracy. Concluding, we
      can say that this trainer-trainee approach is very promising. Future research
      should investigate, whether this approach is superior to conventional training
      approaches. This trainer-trainee concept could have potential for future
      application of BCIs to end users.

PMID- 25570253
TI  - Automatic lung tidal volumes estimation from tracheal sounds.
AB  - This paper presents a method to automatically estimate lung tidal volumes from
      the acoustic signals generated in the respiratory track. The signal is measured
      with an acoustic based sensor placed in the suprasternal notch. The method does
      not require any previous knowledge or modelling of the individual respiratory
      track, and relies on just one calibration parameter. The proposed algorithm is
      tested on 316 respiratory phases obtained from 4 volunteers. The subjects were
      simultaneously wearing a Wright respirometer which was used as a gold standard
      for comparison. Agreement between the two methods was assessed with Bland-Altman
      techniques. The results show the potential the technique has, integrated with a
      small acoustic sensor, for less-intrusive and even remote and/or continuous
      monitoring of lung tidal volumes. 

PMID- 25570254
TI  - Analysis of spontaneous MEG activity in mild cognitive impairment and Alzheimer's
      disease using Jensen's divergence.
AB  - The aim of this study was to analyze the changes that mild cognitive impairment
      (MCI) and Alzheimer's disease (AD) elicit in brain dynamics. For this task, the
      spontaneous magnetoencephalographic (MEG) activity from 36 AD patients, 18 MCI
      subjects and 24 healthy controls was analyzed. A disequilibrium measure, Jensen's
      divergence, was used to estimate the irregularity of neural dynamics. Results
      revealed that AD patients displayed significant changes (p<;0.05) in the patterns
      of irregularity in comparison with MCI subjects and healthy controls. Slight
      differences between MCI subjects and elderly controls were also found. Our
      results suggest that AD progression is accompanied by region-specific patterns of
      abnormalities in the neural activity.

PMID- 25570255
TI  - Automatic detection of the anterior and posterior commissures on MRI scans using
      regression forests.
AB  - Identification of the anterior and posterior commissure is crucial in
      stereotactic and functional neurosurgery, human brain mapping, and medical image
      processing. We present a learning-based algorithm to automatically and rapidly
      localize these landmarks using random forests regression. Given a point in the
      image, we extract a set of multi-scale long-range textural features, and
      associate a probability for this point to be the landmark. We build random
      forests models to learn the relationship between the value of these features and
      the probability of a point to be a landmark point. Three-stage coarse-to-fine
      models are trained for AC and PC separately using down-sampled by 4, down-sampled
      by 2, and the original images. Testing is performed in a hierarchical approach to
      first obtain a rough estimation at the coarse level and then fine-tune the
      landmark position. We extensively evaluate our method in a leave-one-out fashion
      using a large dataset of 100 T1-weighted images. We also compare our method to
      the state-of-art AC/PC detection methods including an atlas-based approach with
      six well-established nonrigid registration algorithms and a publicly available
      implementation of a model-based approach. Our method results in an overall error
      of 0.84+/-0.41mm for AC, 0.83+/-0.36mm for PC and a maximum error of 2.04mm; it
      performs significantly better than the model-based AC/PC detection method we
      compare it to and better than three of the nonrigid registration methods. It is
      much faster than nonrigid registration methods.

PMID- 25570256
TI  - Automatic tracking of intraoperative brain surface displacements in brain tumor
      surgery.
AB  - In brain tumor surgery, soft-tissue deformation, known as brain shift, introduces
      inaccuracies in the application of the preoperative surgical plan and impedes the
      advancement of image-guided surgical (IGS) systems. Considerable progress in
      using patient-specific biomechanical models to update the preoperative images
      intraoperatively has been made. These model-update methods rely on accurate
      intraoperative 3D brain surface displacements. In this work, we investigate and
      develop a fully automatic method to compute these 3D displacements for lengthy
      (~15 minutes) stereo-pair video sequences acquired during neurosurgery. The first
      part of the method finds homologous points temporally in the video and the second
      part computes the nonrigid transformation between these homologous points. Our
      results, based on parts of 2 clinical cases, show that this speedy and promising
      method can robustly provide 3D brain surface measurements for use with model
      based updating frameworks.

PMID- 25570257
TI  - Identification of patterns of gray matter abnormalities in schizophrenia using
      source-based morphometry and bagging.
AB  - Despite its reliable diagnosis, schizophrenia lacks an objective diagnostic test
      or a validated biomarker, which prevents a better understanding of this disorder.
      Structural magnetic resonance imaging (sMRI) has been vastly explored to find
      consistent abnormality patterns of gray matter concentration (GMC) in
      schizophrenia, yet we are far from having reached conclusive evidence. This paper
      presents a machine learning approach based on resampling techniques to find brain
      regions with consistent patterns of GMC differences between healthy controls and
      schizophrenia patients, these regions being detected by means of source-based
      morphometry. This work uses multi-site data from the Mind Clinical Imaging
      Consortium, which is composed of sMRI data from 124 controls and 110 patients.
      Our method achieves a better classification rate than other algorithms and
      detects regions with GMC differences between both groups that are consistent with
      several findings on the literature. In addition, the results obtained on data
      from multiple sites suggest that it may be possible to replicate these results on
      other datasets.

PMID- 25570258
TI  - Exploring difference and overlap between schizophrenia, schizoaffective and
      bipolar disorders using resting-state brain functional networks.
AB  - Schizophrenia, schizoaffective and bipolar disorders share some common symptoms.
      However, the biomarkers underlying those disorders remain unclear. In fact, there
      is still controversy about the schizoaffective disorder with respect to its
      validity of independent category and its relationship with schizophrenia and
      bipolar disorders. In this paper, based on brain functional networks extracted
      from resting-state fMRI using a recently proposed group information guided ICA
      (GIG-ICA) method, we explore the biomarkers for discriminating healthy controls,
      schizophrenia patients, bipolar patients, and patients with two symptom defined
      subsets of schizoaffective disorder, and then investigate the relationship
      between different groups. The results demonstrate that the discriminating regions
      mainly including frontal, parietal, precuneus, cingulate, supplementary motor,
      cerebellar, insular and supramarginal cortices perform well in distinguishing the
      different diagnostic groups. The results also suggest that schizoaffective
      disorder may be an independent disorder, although its subtype characterized by
      depressive episodes shares more similarity with schizophrenia.

PMID- 25570259
TI  - Towards automatic MRI volumetry for treatment selection in acute ischemic stroke
      patients.
AB  - In many tertiary clinical care centers, decision-making and treatment selection
      for acute ischemic stroke is based on magnetic resonance imaging (MRI). The
      "mismatch" concept aims to segregate the infarct core from potentially
      salvageable hypo-perfused tissue, the so-called penumbra that is determined from
      a combination of different MRI modalities. Recent studies have challenged the
      current concept of tissue at risk stratification targeted to identify the best
      treatment options for every individual patient. Here, we propose a novel, more
      elaborate image analysis approach that is based on supervised classification
      methods to automatically segment and predict the extent of the tissue
      compartments of interest (healthy, infarct, penumbra regions). The output of the
      algorithm is a label image including quantitative volumetric information about
      each tissue compartment. The approach has been evaluated on an image dataset of
      10 stroke patients and it compared favorably to currently available tools.

PMID- 25570260
TI  - A method for assessing nonlinear growth in the fetal cortex.
AB  - The cerebral cortex is folded into gyri and sulci in the brains of higher
      mammals. Quantitative study of the process by which the cortex folds during brain
      development is critical to a complete understanding of normal brain development
      and neuro-developmental disorders. In this work, we propose a new method by which
      to localise nonlinearities in the cortical folding process, and thereby identify
      regions of differential growth across the cortex. Our method is based on
      spherical harmonic (SPHARM) representation of the cortical surface. Linearity is
      assessed by comparison of each SPHARM reconstructed surface with an artificial
      surface constructed using a linear combination of SPHARM coefficients from data
      at adjoining developmental time points. The resultant quantification of cortical
      folding development is easy to interpret, and the method has low computational
      cost. We demonstrate application to a set of experimental MRI data of fetal sheep
      brains, across key developmental timepoints as the cortex first folds during
      development. 

PMID- 25570262
TI  - Undersampled dynamic magnetic resonance imaging using kernel principal component
      analysis.
AB  - Compressed sensing (CS) is a promising approach to accelerate dynamic magnetic
      resonance imaging (MRI). Most existing CS methods employ linear sparsifying
      transforms. The recent developments in non-linear or kernel-based sparse
      representations have been shown to outperform the linear transforms. In this
      paper, we present an iterative non-linear CS dynamic MRI reconstruction framework
      that uses the kernel principal component analysis (KPCA) to exploit the
      sparseness of the dynamic image sequence in the feature space. Specifically, we
      apply KPCA to represent the temporal profiles of each spatial location and
      reconstruct the images through a modified pre-image problem. The underlying
      optimization algorithm is based on variable splitting and fixed-point iteration
      method. Simulation results show that the proposed method outperforms conventional
      CS method in terms of aliasing artifact reduction and kinetic information
      preservation.

PMID- 25570261
TI  - Self-navigated low-rank MRI for MPIO-labeled immune cell imaging of the heart.
AB  - Super-paramagnetic iron oxide (SPIO) particles can magnetically label immune
      cells in circulation; the accumulation of labeled cells can then be detected by
      magnetic resonance imaging (MRI). This has enormous potential for imaging
      inflammatory responses in the heart, but it has been difficult to do in vivo
      using conventional free-breathing, ungated cardiac imaging. Subspace imaging with
      temporal navigation and sparse sampling of (k, t)-space has previously been used
      to accelerate several cardiac imaging applications, conventionally alternating
      between acquiring navigator data and sparse data every other TR. Here we describe
      a more efficient self-navigated pulse sequence to acquire both navigator and
      sparse (k, t)-space data in the space of a single TR, doubling imaging speed to
      approach 100 frames per second (fps). We show the feasibility of using the
      resulting method to assess myocardial inflammation in a pre-clinical rodent
      ischemic reperfusion injury (IRI) model using micron-sized paramagnetic iron
      oxide (MPIO) particles to label immune cells in situ.

PMID- 25570263
TI  - R(*)2 mapping for robust brain function detection in the presence of magnetic
      field inhomogeneity.
AB  - T(*)2 mapping or R(*)2 mapping for brain function offers advantages such as
      providing quantitative measurements independent of the MRI acquisition parameters
      (e.g. echo time TE). However, magnetic field susceptibility in the human brain
      can prevent an accurate estimation of R(*)2, which in turn impacts the ability to
      study brain function. The present work investigates the effects of in-plane
      magnetic susceptibility-induced magnetic field gradients on R(*)2 decay. An
      iterative method is developed for R(*)2 estimation with an increased robustness
      to field inhomogeneity. The new method is further tested in a visual fMRI
      experiment with and without magnetic field gradients and its performance is
      compared to a standard BOLD fMRI and a BOLD fMRI based on echo summation. Reduced
      sensitivity in fMRI to in-plane magnetic gradients is obtained with the present
      methodology. 

PMID- 25570264
TI  - Imaging and localizing interventional devices by susceptibility mapping using
      MRI.
AB  - MRI has been used for imaging interventional procedures with devices such as
      brachytherapy seeds, biopsy needles, markers, and stents. However, the high
      susceptibility of these devices leads to signal loss and distortion in the MRI
      images. Previously, we proposed a method to generate positive contrast of the
      brachytherapy seeds using a regularized L1 minimization algorithm. In this paper,
      we further developed and tested the method to image larger interventional devices
      based on susceptibility mapping. Computer simulations and experiments were
      performed using phantoms made of platinum wires and titanium needles. The results
      show that the proposed method provide positive contrast images of devices,
      therefore improves the visualization and localization of the devices.

PMID- 25570266
TI  - Exploiting similarity in adjacent slices for compressed sensing MRI.
AB  - Due to fundamental characteristics of MRI that limit scan speedup, sub-sampling
      techniques such as compressed sensing (CS) have been developed for rapid MRI.
      Current CS MRI approaches utilize sparsity of the image in the wavelet or other
      transform domains to speed-up acquisition. Another drawback of MRI is its poor
      signal-to-noise ratio (SNR), which is proportional to the image slice thickness.
      In this paper, we use the difference between adjacent slices as the sparse domain
      for CS MRI. We propose to acquire thick MRI slices and to reconstruct the thin
      slices from the thick slices' data, utilizing the similarity between adjacent
      thin slices. The acquisition of thick slices, instead of thin ones, improves the
      total SNR of the reconstructed image. Experimental results show that the image
      reconstruction quality of the proposed method outperforms existing CS MRI methods
      using the same number of measurements.

PMID- 25570265
TI  - Accelerated MRI using iterative non-local shrinkage.
AB  - We introduce a fast iterative non-local shrinkage algorithm to recover MRI data
      from undersampled Fourier measurements. This approach is enabled by the
      reformulation of current non-local schemes as an alternating algorithm to
      minimize a global criterion. The proposed algorithm alternates between a non
      local shrinkage step and a quadratic subproblem. The resulting algorithm is
      observed to be considerably faster than current alternating non-local algorithms.
      We use efficient continuation strategies to minimize local minima issues. The
      comparisons of the proposed scheme with state-of-the-art regularization schemes
      show a considerable reduction in alias artifacts and preservation of edges.

PMID- 25570267
TI  - Toward on-chip functional neuronal networks: computational study on the effect of
      synaptic connectivity on neural activity.
AB  - This paper presents a new unified computational-experimental approach to study
      the role of the synaptic activity on the activity of neurons in the small
      neuronal networks (NNs). In a neuronal tissue/organ, this question is
      investigated with higher complexities by recording action potentials from
      population of neurons in order to find the relationship between connectivity and
      the recorded activities. In this approach, we study the dynamics of very small
      cortical neuronal networks, which can be experimentally synthesized on chip with
      constrained connectivity. Multi-compartmental Hodgkin-Huxley model is used in
      NEURON software to reproduce cells by extracting the experimental data from the
      synthesized NNs. We thereafter demonstrate how the type of synaptic activity
      affects the network response to specific spike train using the simulation
      results. 

PMID- 25570268
TI  - Development and calibration of a microfluidic biofilm growth cell with flow
      templating and multi-modal characterization.
AB  - We report the development of a microfluidic flow-templating platform with multi
      modal characterization for studies of biofilms and their precursor materials. A
      key feature is a special three inlet flow-template compartment, which confines
      and controls the location of biofilm growth against a template wall.
      Characterization compartments include Raman imaging to study the localization of
      the nutrient solutions, optical microscopy to quantify biofilm biomass and
      localization, and cyclic voltammetry for flow velocity measurements. Each
      compartment is tested and then utilized to make preliminary measurements. 

PMID- 25570269
TI  - CMOS-based high-speed nanopore recording: signals and systems.
AB  - This paper considers the potential of CMOS-based nanopore measurement systems for
      high-speed molecular recording and DNA sequencing in particular. As such it
      approximates the signal fidelity limitations of a CMOS-based nanopore readout
      channel and discusses the means by which throughput could be increased through
      the use of a parallel CMOS readout system.

PMID- 25570270
TI  - Systematic analysis of microfluidic probe design and operation.
AB  - Microfluidic probes are an emerging tool used in a wide range of applications
      including surface biopatterning, immunohistology, and cell migration studies.
      They control flow above a surface by simultaneously injecting and aspirating
      fluids from a pen-like structure positioned a few tens of microns above a
      surface. Rather than confining flows inside microchannels they rely on
      recirculating flow patterns between the probe tip and the substrate to create a
      hydrodynamic flow confinement (HFC) zone in which reagents can be locally
      delivered to the surface. In this paper, we provide a theoretical model,
      supported by numerical simulations and experimental data, describing the extent
      of the HFC as a function of the two most important probe operation parameters,
      the ratio of aspiration to injection flow rate, and the distance between probe
      apertures. Two types of probes are studied: two-aperture microfluidic probes
      (MFPs) and microfluidic quadrupoles (MQs). In both cases, the model yields very
      accurate results and suggests a simple underlying theory based on 2D potential
      flows to understand probe operation. We further highlight how the model can be
      used to precisely control the probe's "brush stroke" while in surface patterning
      mode. The understanding of probe operation made possible through the provided
      analytical model should lay the bases for computer-controlled probe calibration
      and operation. 

PMID- 25570271
TI  - Poly(3,4-ethylenedioxythiophene)/graphene oxide composite coating for electrode
      tissue interface.
AB  - Owing to interacting with the living tissue directly, the electrode-tissue
      interface largely determines the performance of the whole bioelectronics devices.
      The miniaturization of biomedical electronic components requires interface
      materials to possess properties including excellent electrical performance, good
      biocompatibility and compatibility with microelectronic fabrication process.
      Considering the unique characteristics and wide applications in biomedical domain
      of conducting polymer and graphene, composite film consists of poly(3,4
      ethylenedioxythiophene) (PEDOT) and graphene oxide (GO) is proposed as electrode
      tissue interface in this work. The facilely electrochemically synthesized
      PEDOT/GO coating on microelectrodes shows low impedance, high charge storage
      capacity and good biocompatibility to act as electrode-tissue interface. As a
      result, the composite film is a potential biomaterial as electrode-tissue
      interface for tissue engineering and further implantable electrophysiological
      devices. 

PMID- 25570272
TI  - Intermittent vagal nerve stimulation alters the electrophysiological properties
      of atrium in the myocardial infarction rat model.
AB  - Intermittent vagal nerve stimulation (VNS) has emerged as a potential therapy to
      treat cardiovascular diseases by delivering electrical stimulation to the vagus
      nerves. The purpose of this study was to investigate the electrophysiological
      changes in the atrium resulting from long-term intermittent VNS therapy in the
      chronic myocardial infarction (MI) rat model. MI was induced via left anterior
      descending coronary artery (LAD) ligation in male Sprague-Dawley rats, randomized
      into two groups: MI (implanted with nonfunctional VNS stimulators) and MI-VNS
      (implanted with functional VNS stimulators and received chronic intermittent VNS
      treatment) groups. Further, a sham group was used as control in which MI was not
      performed and received nonfunctional VNS stimulators. At 12 weeks, optical
      mapping of right atrium (RA) of sinus rhythm was performed. Our results
      demonstrated that chronic MI changed the electrical properties of the atrium
      action potentials and resulted in reduced action potential duration at 50%
      (APD50) and 80% (APD80) repolarization. Chronic right cervical VNS restored the
      APD back to healthy heart APD values. Additionally, APD heterogeneity index
      increased as a result of the chronic MI. Chronic VNS was not found to alter this
      increase. By calculating PR intervals from weekly ECG recordings of anaesthetized
      rats, we demonstrated that chronic MI and intermittent VNS did not affect the AV
      conduction time from the atria to the ventricles. From our study, we conclude the
      MI decreased the APD and increased APD spatial dispersion. VNS increased the APD
      back to healthy normal values but did change the APD spatial dispersion and the
      electrical conduction in the RA.

PMID- 25570273
TI  - Fractionated electrograms and rotors detection in chronic atrial fibrillation
      using model-based clustering.
AB  - The identification of atrial fibrillation (AF) substrates is needed to improve
      ablation therapy guided by electrograms, although mechanisms that sustain AF are
      not fully understood. Detection of complex fractionated atrial electrograms
      (CFAE) is used for this purpose. Nonetheless, efficacy of this method is
      inadequate in the case of chronic AF. Recent hypothesis proposes the rotors as
      fibrillatory substrate. Novel approaches seek to relate CFAE with rotor;
      nevertheless, such methods are not able to identify the associated substrate.
      Furthermore, the patterns that characterize CFAE generated by rotors remain
      unknown. Thus, tracking of rotors is an unsolved issue. In this paper, we propose
      a non-supervised method to find patterns associated with fibrillatory substrates
      in chronic AF. We extracted two features based on local activation wave detection
      and one feature based on non-linear dynamics. Gaussian mixture model-based
      clustering was used to discriminate CFAE patterns. Resulting clusters are
      visualized in an electroanatomic map. We assessed the proposed method in a real
      database labeled according to the level of fractionation and in a simulated
      episode of chronic AF in which a rotor was detected. Our results indicate that
      the method proposed can separate different levels of fractionation in CFAE, and
      provide evidence that clustering can be used to locate the vortex of the rotors.
      Provided approach can support ablation therapy procedures by means of CFAE
      patterns discrimination.

PMID- 25570274
TI  - An automated algorithm for determining conduction velocity, wavefront direction
      and origin of focal cardiac arrhythmias using a multipolar catheter.
AB  - Determining locations of focal arrhythmia sources and quantifying myocardial
      conduction velocity (CV) are two major challenges in clinical catheter ablation
      cases. CV, wave-front direction and focal source location can be estimated from
      multipolar catheter data, but currently available methods are time-consuming,
      limited to specific electrode configurations, and can be inaccurate. We developed
      automated algorithms to rapidly identify CV from multipolar catheter data with
      any arrangement of electrodes, whilst providing estimates of wavefront direction
      and focal source position, which can guide the catheter towards a focal
      arrhythmic source. We validated our methods using simulations on realistic human
      left atrial geometry. We subsequently applied them to clinically-acquired
      intracardiac electrogram data, where CV and wavefront direction were accurately
      determined in all cases, whilst focal source locations were correctly identified
      in 2/3 cases. Our novel automated algorithms can potentially be used to guide
      ablation of focal arrhythmias in real-time in cardiac catheter laboratories. 

PMID- 25570275
TI  - Role of atrial tissue substrate and electrical activation pattern in
      fractionation of atrial electrograms: a computational study.
AB  - Complex fractionated atrial electrograms (CFAEs) are often used as a clinical
      marker for re-entrant drivers of atrial fibrillation. However, outcomes of
      clinical ablation procedures based on CFAEs are controversial and the mechanistic
      links between fractionation, re-entrant activity and the characteristics of the
      atrial substrate are not completely understood. We explore such links by
      simulating electrograms arising from both normal and re-entrant electrical
      activity in atrial tissue models. 2D and 3D tissue geometries with a range of
      conditions for intracellular coupling and myofiber orientation fields were
      studied. Electrograms were fractionated in the presence of complex atrial fiber
      fields and in 3D irregular geometries, due to far-field excitations. The
      complexity of the local electrical activity was not a strong determinant of the
      degree of fractionation. These results suggest that electrogram fractionation is
      more strongly linked to atrial substrate characteristics (including tissue
      geometry, fiber orientation and degree of intercelullar coupling) than to the
      electrical activation pattern sustaining atrial fibrillation. 

PMID- 25570276
TI  - A software platform for the comparative analysis of electroanatomic and imaging
      data including conduction velocity mapping.
AB  - Electroanatomic mapping systems collect increasingly large quantities of
      spatially-distributed electrical data which may be potentially further
      scrutinized post-operatively to expose mechanistic properties which sustain and
      perpetuate atrial fibrillation. We describe a modular software platform,
      developed to post-process and rapidly analyse data exported from electroanatomic
      mapping systems using a range of existing and novel algorithms. Imaging data
      highlighting regions of scar can also be overlaid for comparison. In particular,
      we describe the conduction velocity (CV) mapping algorithm used to highlight
      wavefront behaviour. CV was found to be particularly sensitive to the spatial
      distribution of the triangulation points and corresponding activation times. A
      set of geometric conditions were devised for selecting suitable triangulations of
      the electrogram set for generating CV maps. 

PMID- 25570277
TI  - Feature selection for discrimination of fractionation levels in atrial
      electrograms.
AB  - Radiofrequency catheter ablation of atrial fibrillation (AF) guided by complex
      fractionated atrial electrograms (CFAE) is associated with a high AF termination
      rate in paroxysmal AF, but not in persistent. CFAE does not always identify
      favorable sites for persistent AF ablation. Studies suggest that only high
      fractionation level should be used as a target site for ablation. Nonetheless,
      there are not a standardized criterion to defined fractionation levels.
      Therefore, a better characterization of the signal is required providing a set of
      more powerful features that should be extracted from CFAE. Due to the apparent
      difference among fractionation classes in terms of their stochastic variability,
      we test time-domain and time-frequency based feature extraction approaches. Also,
      we carried out the symmetrical uncertainty-based feature selection to determine
      the most relevant features which improve discrimination of fractionation levels.
      Obtained results on a tested real electrogram database show that most relevant
      features in time-domain are related with time intervals and not with amplitudes.
      Nonetheless, time-frequency features obtained more information from the signal
      and this representation is likely a better suitable discriminating approach,
      particularly to detect high fractionated electrograms with a sensitivity and
      specificity of 83.0% and 93.6%, respectively. 

PMID- 25570278
TI  - The dynamic effect of muscle activation on knee stiffness.
AB  - Adapting limb mechanics in a task and environment dependent manner is one
      component of human motor control. Joint mechanics have been extensively studied
      under static postural conditions, but less so under time-varying movement
      conditions. The limited studies that have investigated joint mechanics during
      movement, have found a drop in joint stiffness during movement, however the
      source of this decrease in stiffness remains unknown. Here in this paper we
      investigate whether time-varying muscle activation, which occurs during
      volitional movement, can lead to the drop in stiffness seen during movement. We
      found that under time-varying isometric conditions stiffness dropped when
      subjects transitioned from extension to flexion and vice-versa, a phenomenon that
      could not be explained by simply superimposing extension and flexion
      contractions. These findings suggest that dynamics of muscle activation may be
      responsible for the complex pattern of stiffness changes seen during simple
      movements. Furthermore, these results imply that EMG-based estimates of
      stiffness, which work well for steady-state postural conditions, will need to be
      augmented to account for the highly non-linear relationship between muscle
      activation and stiffness before they can also be used to estimate stiffness
      during dynamic contractions. 

PMID- 25570279
TI  - Identification of ankle joint stiffness during passive movements--a subspace
      linear parameter varying approach.
AB  - This paper describes a novel method for the identification of time-varying ankle
      joint dynamic stiffness during large passive movements. The method estimates a
      linear parameter varying parallel-cascade (LPV-PC) model of joint stiffness
      consisting of two pathways: (a) an LPV impulse response function (IRF) for
      intrinsic mechanics and (b) an LPV Hammerstein cascade with time-varying static
      nonlinearity and a time-invariant linear dynamics for the reflex pathway. A
      subspace identification technique is used to estimate a statespace representation
      of the reflex stiffness dynamics. Then, an orthogonal projection decouples
      intrinsic from reflex response and subsequently identifies an LPV-IRF model of
      intrinsic stiffness. Finally, an LPV model of the reflex static nonlinearity is
      estimated using an iterative, separable least squares method. The LPV method was
      validated using experimental data from two healthy subjects where the ankle was
      moved passively by an actuator through its range of motion first without and then
      with perturbations. The identification results demonstrated that (a) the dynamic
      response of the intrinsic pathway changes systematically with joint position; and
      (b) the static nonlinearity of the reflex pathway resembles a half-wave rectifier
      whose threshold decreases and gain increases as ankle is moved to dorsiflexed
      position. 

PMID- 25570280
TI  - Knee stiffness estimation in physiological gait.
AB  - During physiological gait, humans continuously modulate their knee stiffness,
      depending on the demands of the activity and the terrain. A similar functionality
      could be provided by modern actuators in transfemoral prosthesis. However,
      quantitative data on how knee stiffness is modulated during physiological gait is
      still missing. This is likely due to the experimental difficulties associated
      with identifying knee stiffness by applying perturbations during gait. It is our
      goal to quantify such stiffness modulation during gait without the need to apply
      perturbations. Therefore, we have recently presented an approach to quantify knee
      stiffness from kinematic, kinetic and electromyographic (EMG) measurements, and
      have validated it in isometric conditions. The goal of this paper is to extend
      this approach to non-isometric conditions by combining inverse dynamics and EMG
      measurements, and to quantify physiological stiffness modulation in the example
      of level-ground walking. We show that stiffness varies substantially throughout a
      gait cycle, with a stiffness of around 100 Nm/rad during swing phase, and a peak
      of 450 Nm/rad in stance phase. These quantitative results may be beneficial for
      design and control of transfemoral prostheses and orthoses that aim to restore
      physiological function. 

PMID- 25570281
TI  - Design and characterization of a biologically inspired quasi-passive prosthetic
      ankle-foot.
AB  - By design, commonly worn energy storage and release (ESR) prosthetic feet cannot
      provide biologically realistic ankle joint torque and angle profiles during
      walking. Additionally, their anthropomorphic, cantilever architecture causes
      their mechanical stiffness to decrease throughout the stance phase of walking,
      opposing the known trend of the biological ankle. In this study, the design of a
      quasi-passive pneumatic ankle-foot prosthesis is detailed that is able to
      replicate the biological ankle's torque and angle profiles during walking. The
      prosthetic ankle is comprised of a pneumatic piston, bending spring and solenoid
      valve. The mechanical properties of the pneumatic ankle prosthesis are
      characterized using a materials testing machine and the properties are compared
      to those from a common, passive ESR prosthetic foot. The characterization spanned
      a range of ankle equilibrium pressures and testing locations beneath the foot,
      analogous to the location of center of pressure within the stance phase of
      walking. The pneumatic ankle prosthesis was shown to provide biologically
      appropriate trends and magnitudes of torque, angle and stiffness behavior, when
      compared to the passive ESR prosthetic foot. Future work will focus on the
      development of a control system for the quasi-passive device and clinical testing
      of the pneumatic ankle to demonstrate efficacy.

PMID- 25570282
TI  - Simulation of a powered ankle prosthesis with dynamic joint alignment.
AB  - This paper presents simulations of a new type of powered ankle prosthesis
      designed to dynamically align the tibia with the ground reaction force (GRF)
      vector during peak loading. The functional goal is to reduce the moment
      transferred through the socket to the soft tissue of the residual limb. The
      forward dynamics simulation results show a reduction in socket moment and the
      impact on the pelvis and affected-side knee. This work supports further research
      on transtibial prosthetic designs that are not limited to mimicking
      physiologically normal joint motions to optimize lower limb amputee gait. 

PMID- 25570283
TI  - Effects of functional range of knee extension for transfemoral prosthesis on
      stair ascent motion.
AB  - We previously proposed a passive mechanism as the link knee joint unit (LKJ) for
      a transfemoral prosthesis for stair ascent. The prototype allowed the
      experimental subjects to ascend stairs without the use of a handrail. In the
      present study, we modified the LKJ unit and developed further two designs of the
      LKJ unit. One has full knee extension function during the prosthetic stance phase
      (condition 1). The other design mechanically trades off the functional range of
      knee extension against stability of the LKJ unit (condition 3). In the stair
      ascent experiment with six able-bodied subjects, all subjects succeeded in
      ascending stairs with the three LKJ conditions without the use of a handrail. No
      difference was found in joint angels and joint moments of the intact and
      prosthetic legs among all LKJ conditions. However, subjective assessment for ease
      of LKJ extension during stair ascent showed that the participants felt easier to
      extend the LKJ unit in the condition 1 and 2 than the condition 3. It is
      suggested that the condition 1 or 2 is appropriate for prosthesis users who can
      ascend stairs with the LKJ unit. For prosthesis users who are not familiar with
      the LKJ unit, the condition 3 would be useful to learn how to use it. 

PMID- 25570284
TI  - Low-power hardware implementation of movement decoding for brain computer
      interface with reduced-resolution discrete cosine transform.
AB  - This paper describes a low-power hardware implementation for movement decoding of
      brain computer interface. Our proposed hardware design is facilitated by two
      novel ideas: (i) an efficient feature extraction method based on reduced
      resolution discrete cosine transform (DCT), and (ii) a new hardware architecture
      of dual look-up table to perform discrete cosine transform without explicit
      multiplication. The proposed hardware implementation has been validated for
      movement decoding of electrocorticography (ECoG) signal by using a Xilinx FPGA
      Zynq-7000 board. It achieves more than 56* energy reduction over a reference
      design using band-pass filters for feature extraction. 

PMID- 25570285
TI  - Generalizability of EMG decoding using local field potentials.
AB  - Motor cortical local field potentials (LFPs) have been successfully used to
      decode both kinematics and kinetics of arm movement. For future clinically viable
      prostheses, however, brain activity decoders will have to generalize well under a
      wide spectrum of behavioral conditions. This property has not yet been
      demonstrated clearly. Here, we provide evidence for the first time, that an LFP
      based electromyogram (EMG) decoder can generalize reasonably well across two
      different types of behavior. We implanted intracortical microelectrode arrays in
      the primary motor (M1) and ventral pre-motor (PMv) cortices of a rhesus macaque,
      and recorded LFP and EMG activity from arm and hand muscles of the contralateral
      forelimb during a two-dimensional (2-D) centre-out isometric wrist torque task
      (TT), and during free reach and grasp behavior (FB). Selected temporal and
      spectral features of the LFP signals were used to train EMG decoders using data
      from both types of behavior separately. We assessed the decoding performance for
      both within- and across-task cases. The average achieved generalization score was
      65 +/- 20%, while in many cases individual scores reached 100%. 

PMID- 25570286
TI  - Evaluation of different spelling layouts for SSVEP based BCIs.
AB  - Brain-computer interface (BCI) systems enable humans to communicate with their
      environment by directly using brain signals. This way, body movement is not
      explicitly required for communication making this technology especially useful
      for people with limited mobility. In this study, the system performance and well
      being of 38 subjects are investigated using two different layouts of graphical
      user interfaces (GUI) presented on a computer screen. A steady state visual
      evoked potential (SSVEP) based BCI speller is used. Furthermore, three different
      predefined stimulus frequency sets are tested. Results show that the system works
      best for 55 % of the test subjects using visual stimuli in the range of 8.57 Hz
      15 Hz. The majority of subjects (71 %), prefers the graphical user interface
      layout called Layout 2. Main advantage of this layout is that each desired letter
      or symbol can be selected with only two commands in contrast to Layout 1, where
      usually more than two commands are needed to select a desired object. 

PMID- 25570287
TI  - An adaptive brain-machine interface algorithm for control of burst suppression in
      medical coma.
AB  - Burst suppression is an electroencephalogram (EEG) indicator of profound brain
      inactivation in which bursts of electrical activity alternate with periods of
      isoelectricity termed suppression. Specified time-varying levels of burst
      suppression are targeted in medical coma, a drug-induced brain state used for
      example to treat uncontrollable seizures. A brain-machine interface (BMI) that
      observes the EEG could automate the control of drug infusion rate to track a
      desired target burst suppression trajectory. Such a BMI needs to use models of
      drug dynamics and burst suppression observations, whose parameters could change
      with the burst suppression level and the environment over time. Currently, these
      parameters are fit prior to real-time control, requiring a separate system
      identification session. Moreover, this approach cannot track parameter variations
      over time. In addition, small variations in drug infusion rate may be desired at
      steady state. Here we develop a novel adaptive algorithm for robust control of
      medical coma in face of unknown and time-varying system parameters. We design an
      adaptive recursive Bayesian estimator to jointly estimate drug concentrations and
      system parameters in real time. We construct a controller using the linear
      quadratic-regulator strategy that explicitly penalizes large infusion rate
      variations at steady state and uses the estimates as feedback to generate robust
      control. Using simulations, we show that the adaptive algorithm achieves precise
      control of time-varying target levels of burst suppression even when model
      parameters are initialized randomly, and reduces the infusion rate variation at
      steady state. 

PMID- 25570288
TI  - Long-term decoding of arm movement using Spatial Distribution of Neural Patterns.
AB  - Day to day variability and non-stationarity caused by changes in subject
      motivation, learning and behavior pose a challenge in using local field
      potentials (LFP) for practical Brain Computer Interfaces. Pattern recognition
      algorithms require that the features possess little to no variation from the
      training to test data. As such models developed on one day fail to represent the
      characteristics on the other day. This paper provides a solution in the form of
      adaptive spatial features. We propose an algorithm to capture the local spatial
      variability of LFP patterns and provide accurate long-term decoding. This
      algorithm achieved more than 95% decoding of eight movement directions two weeks
      after its initial training. 

PMID- 25570289
TI  - Upper-limb muscular electrical stimulation driven by EEG-based detections of the
      intentions to move: a proposed intervention for patients with stroke.
AB  - This study proposes an intervention for stroke patients in which electrical
      stimulation of muscles in the affected arm is supplied when movement intention is
      detected from the electroencephalographic signal. The detection relies on the
      combined analysis of two movement related cortical patterns: the event-related
      desynchronization and the bereitschaftspotential. Results with two healthy
      subjects and three chronic stroke patients show that reliable EEG-based
      estimations of the movement onsets can be generated (on average, 66.9 +/- 26.4 %
      of the movements are detected with 0.42 +/- 0.17 false activations per minute)
      which in turn give rise to electrical stimuli providing sensory feedback tightly
      associated to the movement planning (average detection latency of the onsets of
      the movements was 54.4 +/- 287.9 ms). 

PMID- 25570291
TI  - A wearable wireless platform for visually stimulating small flying insects.
AB  - Linking neurons and muscles to their roles in behavior requires not only the
      ability to measure their response during unrestrained movement but also the
      ability to stimulate them and observe the behavioral results. Current wireless
      stimulation technologies can be carried by rodent-sized animals and very large
      insects. However, the mass and volume of these devices make them impractical for
      studying smaller animals like insects. Here we present a battery-powered
      electronics platform suitable to be carried on a flying locust (2.7 g). The
      device has an IR-based (infrared) receiver, can deliver optical or electrical
      stimulation, occupies a volume of 0.1 cm(3), and weighs ~280 mg. We show the
      device is capable of powering two white SMD light emitting diodes (LEDs) for ~4
      min and can be recharged in ~20 min. We demonstrate that our system shows no
      crosstalk with an IR-based Vicon tracking system. The entire package is made from
      commercial off-the-shelf components and requires no microfabrication. 

PMID- 25570290
TI  - Playing checkers with your mind: an interactive multiplayer hardware game
      platform for brain-computer interfaces.
AB  - In this paper we describe a multiplayer brain-computer interface (BCI) based on
      the classic game of checkers using steady-state visually evoked potentials
      (SSVEPs). Previous research in BCI gaming focuses mainly on the production of
      software-based games using a computer screen--few hardware-based BCI games using
      a physical board have been developed. Hardware-based games can present a unique
      set of challenges when compared to software-based games. Depending on where the
      user is sitting, some stimuli might be farther away from the player, at a steeper
      viewing angle, conflated with competing stimuli, or occluded by physical
      barriers. In our game, we light squares on a checkerboard with flickering LEDs to
      elicit SSVEP responses in the subjects. When a subject attends to a particular
      square, the resulting SSVEPs are classified and a robot arm moves the selected
      piece. In a set of pilot experiments we investigated the ability of two subjects
      to use the SSVEP-based hardware game platform, and assessed how interstimulus
      distance, interstimulus angle, distance between target stimulus and subject,
      number of competing stimuli, and visual occlusions of the stimuli influence
      classification accuracy.

PMID- 25570292
TI  - Rewards-driven control of robot arm by decoding EEG signals.
AB  - Decoding the user intention from non-invasive EEG signals is a challenging
      problem. In this paper, we study the feasibility of predicting the goal for
      controlling the robot arm in self-paced reaching movements, i.e., spontaneous
      movements that do not require an external cue. Our proposed system continuously
      estimates the goal throughout a trial starting before the movement onset by
      online classification and generates optimal trajectories for driving the robot
      arm to the estimated goal. Experiments using EEG signals of one healthy subject
      (right arm) yield smooth reaching movements of the simulated 7 degrees of freedom
      KUKA robot arm in planar center-out reaching task with approximately 80% accuracy
      of reaching the actual goal. 

PMID- 25570294
TI  - A visual motion detecting module for dragonfly-controlled robots.
AB  - When imitating biological sensors, we have not completely understood the early
      processing of the input to reproduce artificially. Building hybrid systems with
      both artificial and real biological components is a promising solution. For
      example, when a dragonfly is used as a living sensor, the early processing of
      visual information is performed fully in the brain of the dragonfly. The only
      significant remaining tasks are recording and processing neural signals in
      software and/or hardware. Based on existing works which focused on recording
      neural signals, this paper proposes a software application of neural information
      processing to design a visual processing module for dragonfly hybrid bio-robots.
      After a neural signal is recorded in real-time, the action potentials can be
      detected and matched with predefined templates to detect when and which
      descending neurons fire. The output of the proposed system will be used to
      control other parts of the robot platform. 

PMID- 25570293
TI  - Volitional control of ankle plantar flexion in a powered transtibial prosthesis
      during stair-ambulation.
AB  - Although great advances have been made in the design and control of lower
      extremity prostheses, walking on different terrains, such as ramps or stairs, and
      transitioning between these terrains remains a major challenge for the field. In
      order to generalize biomimetic behaviour of active lower-limb prostheses top-down
      volitional control is required but has until recently been deemed unfeasible due
      to the difficulties involved in acquiring an adequate electromyographic (EMG)
      signal. In this study, we hypothesize that a transtibial amputee can extend the
      functionality of a hybrid controller, designed for level ground walking, to stair
      ascent and descent by volitionally modulating powered plantar-flexion of the
      prosthesis. We here present data illustrating that the participant is able to
      reproduce ankle push-off behaviour of the intrinsic controller during stair
      ascent as well as prevent inadvertent push-off during stair descent. Our findings
      suggest that EMG signal from the residual limb muscles can be used to transition
      between level-ground walking and stair ascent/descent within a single step and
      significantly improve prosthesis performance during stair-ambulation. 

PMID- 25570295
TI  - Towards fenceless boundaries for solar powered insect biobots.
AB  - Demonstration of remote navigation with instrumented insects, such as the
      Madagascar Hissing Cockroach, Gromphadorhina portentosa, has enabled the concept
      of biobotic agents for search and rescue missions and environmental monitoring
      applications. The biobots can form the nodes of a mobile sensor network to be
      established, for example, in unknown and dynamic environments after natural
      disasters to pinpoint surviving victims. We demonstrate here, for the first time,
      the concept of an invisible fence for insect biobots with an ultimate goal of
      keeping insect biobots within a certain distance of each other or a base station
      to ensure a reliable wireless network. For extended mission durations, this
      fenceless boundary would also be used to guide insects towards light sources for
      autonomous solar charging of their on-board batteries. 

PMID- 25570296
TI  - Novel wearable EMG sensors based on nanowire technology.
AB  - Wearable electrodes made of silver nanowires (AgNWs) have demonstrated great
      potential for sensing a variety of physical and physiological signals. This paper
      aimed to study the feasibility of AgNWs electrodes for measuring surface
      electromyographic (sEMG) signals. One human subject was recruited and instructed
      to perform wrist extension repetitively or to produce no movement in the
      experiment. sEMG signals were collected from the right extensor digitorum
      communis of the human subject by an AgNWs electrode and a commercially available
      Ag/AgCl wet sEMG electrode, separately. The quality of recorded sEMG in time and
      frequency domains was compared between the two types of electrodes. The results
      showed that the sEMG signals recorded by the AgNW electrode were comparable with
      that by the Ag/AgCl electrode. Since the dry AgNWs electrodes are flexible,
      wearable, and potentially robust for daily use, novel AgNW-based EMG electrodes
      are promising for many biomedical applications, such as myoelectric control of
      artificial limbs. 

PMID- 25570297
TI  - Implementation of a microfluidic conductivity sensor -- a potential sweat
      electrolyte sensing system for dehydration detection.
AB  - As dehydration continues to plague performance athletes and soldiers, the need
      for improved dehydration detection is clear. We propose the use of a
      conductometric sensor as the foundation of a sweat-sensing patch to address this
      need. The conductometric sensor evaluates the conductivity of solutions with
      varying sodium concentrations. A lithographic process was used to fabricate a
      Polydimethylsiloxane (PDMS) microfluidic channel through which solution was
      flowed. The ionization of the solution that occurs when a voltage is applied
      results in an effective resistance across the channel. The measured resistance
      therefore, reflects the ionization of the solution and the corresponding sodium
      concentration. The potential application of the conductometric sensor in a sweat
      sensing patch requires compatibility with a microcontroller and Bluetooth module.
      Thus, a circuit interface was created. A voltage divider was utilized to convert
      the output resistance of the sensor to a voltage that could be input into a
      microcontroller. An AC voltage signal with a frequency of 10 kHz was used as the
      source voltage of the voltage divider to minimize the faradaic impedance and the
      double layer effect of the ionized solution. Tests have revealed that the
      conductometric is capable of precisely measuring the conductivity of a sodium
      solution. The conductometric sensor will be applied to a sweat sensing patch
      through future work involving studying the link between sodium concentration in
      sweat and an individual's dehydration level, developing a sweat-collection
      method, and developing a method of consideration for the other ions contained in
      sweat. 

PMID- 25570298
TI  - Neonatal heartbeat annunciator for use in the developing world.
AB  - The majority of neonatal deaths occur in the developing countries. In many cases,
      unresponsive infants at birth are alive although birth attendants think they are
      dead and do not attempt to resuscitate them. In order to address this problem,
      training for birth attendant skills for resuscitation and having a device to
      determine the newborn heartbeat are necessary. In this project, a neonatal
      heartbeat annunciator has been designed and undergone preliminary evaluation. The
      device is quickly attached and uses electrodes to pick up the ECG signal from the
      infant's chest. Following electronic processing, the heartbeat is indicated as a
      flash of LED light and the sound of a high-frequency buzzer. It is hoped that
      this device will encourage birth attendants to attempt to resuscitate
      unresponsive babies and help to reduce neonatal mortality. 

PMID- 25570299
TI  - A method for quantitative assessment of artifacts in EEG, and an empirical study
      of artifacts.
AB  - Wearable EEG systems for continuous brain monitoring is an emergent technology
      that involves significant technical challenges. Some of these are related to the
      fact that these systems operate in conditions that are far less controllable with
      respect to interference and artifacts than is the case for conventional systems.
      Quantitative assessment of artifacts provides a mean for optimization with
      respect to electrode technology, electrode location, electronic instrumentation
      and system design. To this end, we propose an artifact assessment method and
      evaluate it over an empirical study of 3 subjects and 5 different types of
      artifacts. The study showed consistent results across subjects and artifacts. 

PMID- 25570300
TI  - Performance evaluation of carbon black based electrodes for underwater ECG
      monitoring.
AB  - Underwater electrocardiogram (ECG) monitoring currently uses Ag/AgCl electrodes
      and requires sealing of the electrodes to avoid water intrusion, but this
      procedure is time consuming and often results in severe irritations or even
      tearing of the skin. To alleviate these problems, our research team developed
      hydrophobic electrodes comprised of a mixture of carbon black powder (CB) and
      polydimethylsiloxane (PDMS) that provide all morphological waveforms without
      distortion of an ECG signal for dry and water-immersed conditions. Performance
      comparison of CB/PDMS electrodes to adhesive Ag/AgCl hydrogel electrodes was
      carried out in three different scenarios which included recordings from a dry
      surface, water immersion, and post-water immersion conditions. CB/PDMS electrodes
      were able to acquire ECG signals highly correlated with those from adhesive
      Ag/AgCl electrodes during all conditions. Statistical reduction in ECG amplitude
      (p<0.05) was only found during the immersed condition with CB/PDMS electrodes
      when compared to Ag/AgCl electrodes sealed with their waterproof adhesive tape.
      Besides this reduction readability of the recordings was not obscured and all
      morphological waveforms of the ECG signal were discernible. The advantages of our
      CB/PDMS electrodes are that they are reusable, can be fabricated economically,
      and most importantly, high-fidelity underwater ECG signals can be acquired
      without relying on the heavy use of waterproof sealing.

PMID- 25570301
TI  - A multi-pair electrode based impedance sensing biopsy needle for tissue
      discrimination during biopsy process.
AB  - We demonstrate the biopsy needle integrated with multi-pair electrode based
      impedance sensing device for biological tissue discrimination. The impedance
      sensing biopsy needle has several pairs of electrodes which enable the selective
      tissue analysis during biopsy process. In order to verify the usefulness of the
      device, we demonstrate the conductance measurement of various saline solutions
      and the real-time conductance monitoring of soft elastomeric materials during the
      needle insertion. Finally, the tissue discrimination of porcine meat tissues
      during the needle insertion was successfully carried out. 

PMID- 25570302
TI  - A multi-band environment-adaptive approach to noise suppression for cochlear
      implants.
AB  - This paper presents an improved environment-adaptive noise suppression solution
      for the cochlear implants speech processing pipeline. This improvement is
      achieved by using a multi-band data-driven approach in place of a previously
      developed single-band data-driven approach. Seven commonly encountered noisy
      environments of street, car, restaurant, mall, bus, pub and train are considered
      to quantify the improvement. The results obtained indicate about 10% improvement
      in speech quality measures. 

PMID- 25570303
TI  - Feedback stimulation strategy: control of retinal ganglion cells activation.
AB  - It is possible to cause a sensation of light in patients who have lost
      photoreceptors due to degenerative eye diseases by targeting surviving neurons
      with electrical stimulation by means of visual prosthetic devices. All
      stimulation strategies in currently used visual prostheses are open-loop, that
      is, the stimulation parameters do not depend on the level of activation of
      neurons surrounding stimulating electrodes. In this paper, we investigate a
      closed-loop stimulation strategy using computer simulations of previously
      constrained models of ON and OFF retinal ganglion cells. Using a proportional
      integral-type controller we show that it is possible to control activation level
      of both types of retinal ganglion cells. We also demonstrate that the controller
      tuned for a particular combination of synaptic currents continues to work during
      retina degeneration when excitatory currents are reduced by 20%. 

PMID- 25570304
TI  - Efficacy of electrical stimulation of retinal ganglion cells with temporal
      patterns resembling light-evoked spike trains.
AB  - People with degenerative retinal diseases such as retinitis pigmentosa lose most
      of their photoreceptors but retain a significant proportion (~30%) of their
      retinal ganglion cells (RGCs). Microelectronic retinal prostheses aim to bypass
      the lost photoreceptors and restore vision by directly stimulating the surviving
      RGCs. Here we investigate the extent to which electrical stimulation of RGCs can
      evoke neural spike trains with statistics resembling those of normal visually
      evoked responses. Whole-cell patch clamp recordings were made from individual cat
      RGCs in vitro. We first recorded the responses of each cell to short sequences of
      visual stimulation. These responses were converted to trains of electrical
      stimulation that we then presented to the same cell via an epiretinal stimulating
      electrode. We then quantified the efficacy of the electrical stimuli and the
      latency of the evoked spikes. In all cases, spikes were evoked with sub
      millisecond latency (0.55 ms, median, ON cells, n = 8; 0.75 ms, median, OFF
      cells, n = 6) and efficacy ranged from 0.4-1.0 (0.79, median, ON cells; 0.97,
      median, OFF cells). These data demonstrate that meaningful spike trains,
      resembling normal responses of RGCs to visual stimulation, can be reliably evoked
      by epiretinal prostheses. 

PMID- 25570305
TI  - Pulse count modulation based biphasic current stimulator for retinal prosthesis
      and in vitro experiment using rd1 mouse.
AB  - For a retinal prosthesis, retinal nerve cells are electrically stimulated by
      current pulses. Typically, the amplitude of the current pulses is modulated to
      control the amount of injected charges. However, a high spatial resolution can be
      difficult to achieve with this amplitude modulation method, because the neural
      response spreads more widely as the amplitude of the current pulses is increased.
      In this paper, a biphasic current stimulator integrated circuit (IC) using a new
      modulation method called, the pulse count modulation, is proposed. In the pulse
      count modulation method, the amplitude and the width of the current pulses are
      fixed, and the amount of injected charges is controlled by the number of applied
      current pulses in a base period. The proposed stimulator IC is fabricated by a
      0.35 MUm bipolar-CMOS-DMOS (BCDMOS) technology. The operation and performance of
      the stimulator IC are evaluated in an in vitro experiment environment with rd 1
      mice. It is shown that a higher spatial resolution can be achieved compared with
      the amplitude modulation method. 

PMID- 25570306
TI  - A cortical integrate-and-fire neural network model for blind decoding of visual
      prosthetic stimulation.
AB  - We present a computational model of the optic pathway which has been adapted to
      simulate cortical responses to visual-prosthetic stimulation. This model
      reproduces the statistically observed distributions of spikes for cortical
      recordings of sham and maximum-intensity stimuli, while simultaneously generating
      cellular receptive fields consistent with those observed using traditional visual
      neuroscience methods. By inverting this model to generate candidate phosphenes
      which could generate the responses observed to novel stimulation strategies, we
      hope to aid the development of said strategies in-vivo before being deployed in
      clinical settings. 

PMID- 25570307
TI  - Simulated prosthetic vision: improving text accessibility with retinal
      prostheses.
AB  - Image processing can improve significantly the every-day life of blind people
      wearing current and upcoming retinal prostheses relying on an external camera. We
      propose to use a real-time text localization algorithm to improve text
      accessibility. An augmented text-specific rendering based on automatic text
      localization has been developed. It has been evaluated in comparison to the
      classical rendering through a Simulated Prosthetic Vision (SPV) experiment with
      16 subjects. Subjects were able to detect text in natural scenes much faster and
      further with the augmented rendering compared to the control rendering. Our
      results show that current and next generation of low resolution retinal
      prostheses may benefit from real-time text detection algorithms. 

PMID- 25570308
TI  - Application of dynamical analyses of heart rate to rhythm classification and
      prognosis.
AB  - We have developed numerical approaches to dynamical analysis of heart rates,
      measured as interbeat or RR, intervals, based on entropy and fluctuation analyses
      in a large data base of consecutive Holter monitor recordings. In Part I, we
      present a RR interval-based classifier that distinguishes normal sinus rhythm
      (NSR), atrial fibrillation (AF) and sinus rhythm with ectopy with an accuracy of
      99%, 81% and 77%respectively, using 10-minute segments. In Part II, we present 2
      year mortality estimation based on the entropy calculations. The major finding is
      that normal dynamics identify a very low risk group. Taken together, these
      results point to automated analysis of heart rate time series with important
      clinical applications. 

PMID- 25570309
TI  - Validation of two novel monitoring devices to measure physical activity in
      healthy women.
AB  - Measurement of physical activity is increasingly important in health research. We
      sought to determine the accuracy and sensitivity to non-exercise activity of
      three activity monitors worn simultaneously by healthy adult women participating
      in a structured activity protocol. Ten normal-weight women wore the Intelligent
      Device for Energy Expenditure and Activity (IDEEA), the SmartShoe, and the
      SenseWear Armband, during activities that included standing, sitting still,
      sitting and fidgeting, lying down, and walking at varying speeds. Percentage of
      time postures correctly identified was determined for the IDEEA and the
      SmartShoe, and activity counts collected from all three devices were compared.
      Posture was detected with high accuracy by both the IDEEA and the SmartShoe
      (97.4% and 94.2% accuracy, respectively). The SmartShoe showed superior
      sensitivity to movement while seated ("fidgeting") compared with the IDEEA
      (p=0.004 and 0.049 difference between postures, respectively); all three devices
      distinguished between fast and slow walking. Data support the ability of the
      IDEEA and the SmartShoe to recognize basic postures in healthy normal-weight
      women, as well as to detect fidgeting within the seated position. 

PMID- 25570310
TI  - Characterization of wheelchair maneuvers based on noisy inertial sensor data: a
      preliminary study.
AB  - A wheelchair user's activity and mobility level is an important indicator of
      his/her quality of life and health status. To assess the activity and mobility
      level, wheelchair maneuvering data must be captured and analyzed. Recently, the
      inertial sensors, such as accelerometers, have been used to collect wheelchair
      maneuvering data. However, these sensors are sensitive to noises, which can lead
      to inaccurate analysis results. In this study, we analyzed the characteristics of
      wheelchair maneuvering data and developed a novel machine-learning algorithm,
      which could classify wheelchair maneuvering data into a series of wheelchair
      maneuvers. The use of machine-learning techniques empowers our approach to
      tolerate noises by capturing the patterns of wheelchair maneuvers. Experimental
      results showed that the proposed algorithm could accurately classify wheelchair
      maneuvers into eight classes, i.e., stationary, linear acceleration/deceleration,
      linear constant speed, left/right turns, and left/right spot turns. The fine
      grained analysis on wheelchair maneuvering data can depict a more comprehensive
      picture of wheelchair users' activity and mobility levels, and enable the
      quantitative analysis of their quality of life and health status. 

PMID- 25570311
TI  - Improving rehabilitation exercise performance through visual guidance.
AB  - In current physical rehabilitation protocols, patients typically perform
      exercises without feedback or guidance following the initial demonstrations from
      the physiotherapist. This paper proposes a system providing continuous visual
      feedback and guidance to patients to improve quality of motion performance and
      adherence to instructions. The system consists of body-worn inertial measurement
      units which continuously measure the patient's pose. The measured pose is
      overlaid with the instructed motion on a visual display shown to the user during
      exercise performance. Two user studies were conducted with healthy participants
      to evaluate the usability of the visual guidance tool. Motion data was collected
      by the inertial measurement sensors and used to evaluate quality of motion,
      comparing user performance with and without visual feedback and with or without
      exercise guidance. The quantitative and qualitative results of the studies
      confirm that performing the exercises with the visual guidance tool promotes more
      consistent exercise performance and proper technique. 

PMID- 25570312
TI  - A study on the use of PPG in quantifying circulatory disruptions.
AB  - We explore the use of photoplethysmography to monitor and detect changes in
      arterial and venous circulation for potential use in surgical flap monitoring.
      The typical disruptions in circulation that are seen in a flap are emulated by
      occlusion tests conducted in controlled settings. Arterial and venous occlusions
      are performed on a limited number of subjects, and associated changes in the PPG
      signals captured at the specific region of interest are analysed. A set of
      parameters that can be used to distinguish between arterial and venous occlusions
      are identified and quantified. These parameters may be used to detect thrombosis
      and differentiate between an arterial and a venous thrombosis in free flaps
      during postoperative monitoring after reconstructive surgery. 

PMID- 25570313
TI  - A multi-parameters fusion model for non-invasive detection of intracranial
      pressure.
AB  - On the basis of discussing the limitation of a single intracranial pressure non
      invasive detection method in clinical application, the feasibility of the
      measurement and analysis model is investigated based on multi-parameters organic
      integration facing to intracranial pressure non-invasive measurement. Then the
      sensitivity analysis for the relation between the detected parameters and the
      change of intracranial pressure will be done. Finally, a synthesized non-invasive
      evaluation frame for intracranial pressure measurement with disease-adaptive
      model choice will be realized. By this way, a new idea is provided for the
      realization of the non-invasive measurement of intracranial pressure and its
      clinical application, which will be of significance for improving the clinical
      feasibility and monitoring accuracy of intracranial pressure non-invasive
      measuring methods. 

PMID- 25570314
TI  - A framework for harmonizing sensor data to support embedded health assessment.
AB  - The use of in-home and mobile sensing is likely to be a key component of future
      care and has recently been studied by many research groups world-wide.
      Researchers have shown that embedded sensors can be used for health assessment
      such as early illness detection and the management of chronic health conditions.
      However, research collaboration and data sharing have been hampered by disparate
      sets of sensors and data collection methods. To date, there have been no studies
      to investigate common measures that can be used across multiple sites with
      different types of sensors, which would facilitate large scale studies and reuse
      of existing datasets. In this paper, we propose a framework for harmonizing
      heterogeneous sensor data through an intermediate layer, the Conceptual Sensor,
      which maps physical measures to clinical space. Examples are included for sleep
      quality and ambulatory physical function. 

PMID- 25570315
TI  - Activity of Daily Living assessment through wireless sensor data.
AB  - Activity of Daily Living has become a clinical de facto instrument to assess
      daily functional status of older people living independently at home. Almost all
      ADLs scales are based on subjective assessment of clinical staff and self
      reported responses of the elderly person. A great deal of variability in ADL
      assessment is likely due to the different cultural beliefs, language and
      education, and over-assessment of personal capability to potentially avoid
      negative consequences. This paper proposes automatic and objective ADLs
      assessment as key component of a technology platform that supports older people
      to live independently in their home, called Smarter Safer Homes. The objective
      ADL assessment is achieved through communicating data from simple non-intrusive,
      wireless sensors placed in a home environment. Pilot sensor data sets were
      collected over six months from nine independent living homes of participants aged
      70+ year. The application of a clustering based, unsupervised learning method on
      these data sets demonstrates the potential to automatically detect five domains
      of activity contributing to functional independence. Furthermore, the method
      provides features that support elderlys self-monitoring of daily activities more
      regularly, that could provide the potential for timely and early intervention
      from family and carers. 

PMID- 25570316
TI  - Pilot evaluation of an unobtrusive system to detect falls at nighttime.
AB  - Research shows that older people (aged 65 years and over) suffer many
      unintentional indoor falls which often lead to severe injuries. As a result of an
      increasingly aged population in developed countries, a sizable portion of
      healthcare funding is consumed in the treatment of fall-related injuries and
      associated long-term care. Detecting falls soon after they occur can be
      potentially live saving. In addition, early treatment of fall-related injuries
      can reduce treatment costs by minimizing health deterioration resulting from long
      periods spent incapacitated on the floor after a fall (a scenario known as a
      'long lie') and decreasing the number of hospital bed-days required. In this
      study, a previously proposed unobtrusive nighttime fall detection system based on
      wireless passive infrared sensors and furniture load sensors is evaluated in a
      pilot study involving three older subjects, monitored for a combined total of 174
      days. No falls occurred during the study. The system reported a false alarm rate
      of 0.53 falls per day, which is comparable with similar unobtrusive and wearable
      sensor fall detection solutions. 

PMID- 25570317
TI  - Ambient intelligence might support increased longevity.
AB  - Several technologies entered our homes to change our lives. First electricity
      brought light and comfort, now communication technologies are transforming our
      living place into a connected place allowing new services to be invented,
      comfort, security, wellness and health services. The ICTs in homes can now help
      prolonge our longevity. 

PMID- 25570318
TI  - Use of a consumer market activity monitoring and feedback device improves
      exercise capacity and activity levels in COPD.
AB  - COPD is associated with a gradual decline in physical activity, which itself
      contributes to a worsening of the underlying condition. Strategies that improve
      physical activity levels are critical to halt this cycle. Wearable sensor based
      activity monitoring and persuasive feedback might offer a potential solution.
      However it is not clear just how much intervention might be needed in this regard
      - i.e. whether programmes need to be tailored specifically for the target
      clinical population or whether more simple activity monitoring and feedback
      solutions, such as that offered in consumer market devices, might be sufficient.
      This research was carried out to investigate the impact of 4 weeks of using an
      off the shelf consumer market activity monitoring and feedback application on
      measures of physical activity, exercise capacity, and health related quality of
      life in a population of 10 Stage I and II COPD patients. Results demonstrate a
      significant and positive effect on exercise capacity (measured using a 6-minute
      walk test) and activity levels (measured in terms of average number of steps per
      hour) yet no impact on health related quality of life (St Georges Respiratory
      Disease Questionnaire). 

PMID- 25570319
TI  - Preliminary study of unobtrusive monitoring to increase safety in daily living.
AB  - An unobtrusive system for monitoring the activities of daily living was developed
      to improve safety and quality of life. The system was used to monitor walking and
      safety while bathing. To monitor waking, a matrix array of pyro-electric sensors
      was installed on the ceiling; to prevent drowning, an accelerometer was installed
      in the bathtub. The matrix of pyro-electric sensors estimated the walking speed
      at home and the accelerometer detected the respiratory rate (RR) and apnea. This
      system might be effective for promoting health in the home. 

PMID- 25570320
TI  - Latent topic discovery of clinical concepts from hospital discharge summaries of
      a heterogeneous patient cohort.
AB  - Patients in critical care often exhibit complex disease patterns. A fundamental
      challenge in clinical research is to identify clinical features that may be
      characteristic of adverse patient outcomes. In this work, we propose a data
      driven approach for phenotype discovery of patients in critical care. We used
      Hierarchical Dirichlet Process (HDP) as a non-parametric topic modeling technique
      to automatically discover the latent "topic" structure of diseases, symptoms, and
      findings documented in hospital discharge summaries. We show that the latent
      topic structure can be used to reveal phenotypic patterns of diseases and
      symptoms shared across subgroups of a patient cohort, and may contain prognostic
      value in stratifying patients' post hospital discharge mortality risks. Using
      discharge summaries of a large patient cohort from the MIMIC II database, we
      evaluate the clinical utility of the discovered topic structure in identifying
      patients who are at high risk of mortality within one year post hospital
      discharge. We demonstrate that the learned topic structure has statistically
      significant associations with mortality post hospital discharge, and may provide
      valuable insights in defining new feature sets for predicting patient outcomes. 

PMID- 25570321
TI  - Remote health monitoring: predicting outcome success based on contextual features
      for cardiovascular disease.
AB  - Current studies have produced a plethora of remote health monitoring (RHM)
      systems designed to enhance the care of patients with chronic diseases. Many RHM
      systems are designed to improve patient risk factors for cardiovascular disease,
      including physiological parameters such as body mass index (BMI) and waist
      circumference, and lipid profiles such as low density lipoprotein (LDL) and high
      density lipoprotein (HDL). There are several patient characteristics that could
      be determining factors for a patient's RHM outcome success, but these
      characteristics have been largely unidentified. In this paper, we analyze results
      from an RHM system deployed in a six month Women's Heart Health study of 90
      patients, and apply advanced feature selection and machine learning algorithms to
      identify patients' key baseline contextual features and build effective
      prediction models that help determine RHM outcome success. We introduce Wanda
      CVD, a smartphone-based RHM system designed to help participants with
      cardiovascular disease risk factors by motivating participants through wireless
      coaching using feedback and prompts as social support. We analyze key contextual
      features that secure positive patient outcomes in both physiological parameters
      and lipid profiles. Results from the Women's Heart Health study show that health
      threat of heart disease, quality of life, family history, stress factors, social
      support, and anxiety at baseline all help predict patient RHM outcome success. 

PMID- 25570322
TI  - Classification of cycling exercise status using short-term heart rate
      variability.
AB  - Introduction of effective home-based exercise programs in older adults and people
      with chronic conditions requires implementation of appropriate safeguards to
      prevent possible side effects of strenuous exercise. In each exercise program the
      following exercise modes can be generally recognized: rest, main exercise, and
      exercise recovery. However, approaches for automated identification of these
      exercise modes have not been studied systematically. The primary purpose of this
      study was (1) to assess whether time-domain HRV parameters differ depending on
      exercise mode; (2) to identify optimal set of time-domain parameters for
      automated classification of exercise mode and build a classification model. Using
      discriminant analysis, two HRV parameters (RRtri and MeanRR) were identified
      which yielded 80% classification success in identifying correct exercise mode by
      applying generated discriminant functions. 

PMID- 25570323
TI  - Analyzing center of pressure progression during bed exits.
AB  - This paper presents a new approach for analyzing center of pressure (COP)
      progression using pressure data collected from a pressure-sensitive array placed
      under the bed mattress. Pressure data were collected from a young female
      participant who was healthy and an older 78 year old female participant who had a
      history of falls. Information relevant to movement direction, time, path
      trajectory, magnitude and frequency was presented in three dimensional plots and
      color differentiated displays. When tested on data collected from an older
      participant who experienced a fall, this method of analyzing COP was able to
      illustrate distinct differences in bed exit patterns used pre and post fall
      episode. This analysis approach shows the potential to detect changes in bed exit
      patterns indicative of a critical health event. Future applications include home
      monitoring to assist with early intervention in the event of bed mobility
      decline. 

PMID- 25570324
TI  - Risk prediction for heart failure incidence within 1-year using clinical and
      laboratory factors.
AB  - Validated risk scores for heart failure incidence are still lacking, especially
      for short-term prediction. In this paper we aim at developing a 1-year risk
      prediction model for heart failure (HF) incidence using both clinical risk
      factors and laboratory variables. The public MIMIC II clinical database is
      studied. Two multivariable Cox models are built to assess the 1-year risk of HF,
      one with conventional clinical risk factors only, another combined with
      laboratory parameters, including serum creatinine (SCR), blood urea nitrogen
      (BUN), glucose, prothrombin time (PT), activated partial thromboplstin time
      (APTT) and total bilirubin (TBIL). The discrimination performances of the
      different models are internally validated at last with bootstrapping. In addition
      to known risk factors, more clinical and laboratory indices, including pulmonary
      circulation diseases, peripheral vascular disease, chronic pulmonary disease,
      hypothyroidism, electrolyte and fluid disorders, BUN and APTT are identified to
      be independent predictors of heart failure incidence. Moreover, we found that the
      long-term risk factor, hypertension, has opposite effect on short-term risk. The
      C-statistics of 0.712 with internal validation has demonstrated the effectiveness
      of the prediction model combined clinical and laboratory factors. 

PMID- 25570325
TI  - Discrimination ability and reproducibility of a new index reflecting autonomic
      nervous function based on pulsatile amplitude of photoplethysmography.
AB  - A new physiological index (MU(PA)) is proposed to represent the autonomic nervous
      system (ANS) function. The index MU(PA) is defined as the natural logarithm of
      the ratio between two different frequency components of the pulsatile amplitude
      of the photoplethysmogram (PPG) signal. The discrimination ability and the
      reproducibility of MU(PA) have been compared with other traditional ANS indices.
      In the experiment, the electrocardiogram, the PPG and continuous blood pressure
      were measured in 59 healthy young subjects (age 25.7 +/- 6.3) and 86 healthy
      elderly subjects (age 70.2 +/- 4.1) at rest. The discrimination ability and the
      reproducibility were evaluated by Cohen's d between young and elderly groups and
      by the interclass correlation coefficient, respectively. The results showed that
      the elderly subjects were significantly (p<;0.001) lower than young subjects in
      MU(PA) and a few traditional indices introduced to be compared with MU(PA).
      Therefore, it suggests that MU(PA) is associated with the decrease in the ANS
      function accompanied by aging. Moreover, it showed that the discrimination
      ability and the reproducibility of the proposed index are comparable or larger
      than those of traditional indices. The proposed index based on the PPG signal
      will be applied to tele-healthcare systems for monitoring people's health in
      daily life in combination with the ratio of the standard deviation of the R-R
      intervals to their average value (CVRR).

PMID- 25570326
TI  - Biomedical Engineering curriculum at UAM-I: a critical review.
AB  - The Biomedical Engineering (BME) curriculum at Universidad Autonoma Metropolitana
      (UAM) has undergone at least four major transformations since the founding of the
      BME undergraduate program in 1974. This work is a critical assessment of the
      curriculum from the point of view of its results as derived from an analysis of,
      among other resources, institutional databases on students, graduates and their
      academic performance. The results of the evaluation can help us define admission
      policies as well as reasonable limits on the maximum duration of undergraduate
      studies. Other results linked to the faculty composition and the social
      environment can be used to define a methodology for the evaluation of teaching
      and the implementation of mentoring and tutoring programs. Changes resulting from
      this evaluation may be the only way to assure and maintain leadership and
      recognition from the BME community. 

PMID- 25570327
TI  - Bioelectricity-AQA, one of the first MOOC courses in engineering.
AB  - Bioelectricity-AQA was one of the first massively open online courses in
      engineering, having been given the first time via Coursera starting in September,
      2012. This report provides some detail on its background, presentation,
      enrollment, and lessons learned. 

PMID- 25570329
TI  - Fuzzy Cognitive Map scenario-based medical decision support systems for
      education.
AB  - Soft Computing (SC) techniques are based on exploiting human knowledge and
      experience and they are extremely useful to model any complex decision making
      procedure. Thus, they have a key role in the development of Medical Decision
      Support Systems (MDSS). The soft computing methodology of Fuzzy Cognitive Maps
      has successfully been used to represent human reasoning and to infer conclusions
      and decisions in a human-like way and thus, FCM-MDSSs have been developed. Such
      systems are able to assist in critical decision-making, support diagnosis
      procedures and consult medical professionals. Here a new methodology is
      introduced to expand the utilization of FCM-MDSS for learning and educational
      purposes using a scenario-based learning (SBL) approach. This is particularly
      important in medical education since it allows future medical professionals to
      safely explore extensive "what-if" scenarios in case studies and prepare for
      dealing with critical adverse events. 

PMID- 25570328
TI  - Learning ultrasound gesture database: building and application to musculoskeletal
      ultrasound exams.
AB  - Our aim is to develop a frame work for virtually learning the ultrasound exams.
      In this paper we address the method used to build the image database required for
      this frame work. The used materiel and the proposed methodology are presented and
      explained. The realized prototype has been used to build the database of
      ultrasound images. 

PMID- 25570330
TI  - STEM promotion through museum exhibits on cardiac monitoring & cardiac rhythm
      management.
AB  - Formal education in science, technology, engineering and math (STEM) does not
      successfully engage all of the students who have potential to become skilled in
      STEM activities and careers. Museum exhibits may be able to reach and engage a
      broader range of the public. STEM Exhibits that are both understandable and
      capture the imagination of viewers may contribute toward increased interest in
      STEM activities. One such topic for such an exhibit could be cardiac pacemakers
      and cardioverter defibrillators that sustain life. Although museums have existed
      for centuries, the available types of exhibit designs has dramatically increased
      in recent decades due to innovations in technology. Science and technology
      museums have especially taken advantage of the progression of exhibit design to
      developed new ways to communicate to their viewers. These novel presentation
      tools allow museums to more effectively convey to and engage viewers. This paper
      examines the techniques employed by museums in exhibits and considers the
      practices of several museums with exhibits related to cardiac monitoring (CM) and
      cardiac rhythm management (CRM). 

PMID- 25570331
TI  - The community FabLab platform: applications and implications in biomedical
      engineering.
AB  - Skill development in science, technology, engineering and math (STEM) education
      present one of the most formidable challenges of modern society. The Community
      FabLab platform presents a viable solution. Each FabLab contains a suite of
      modern computer numerical control (CNC) equipment, electronics and computing
      hardware and design, programming, computer aided design (CAD) and computer aided
      machining (CAM) software. FabLabs are community and educational resources and
      open to the public. Development of STEM based workforce skills such as digital
      fabrication and advanced manufacturing can be enhanced using this platform.
      Particularly notable is the potential of the FabLab platform in STEM education.
      The active learning environment engages and supports a diversity of learners,
      while the iterative learning that is supported by the FabLab rapid prototyping
      platform facilitates depth of understanding, creativity, innovation and mastery.
      The product and project based learning that occurs in FabLabs develops in the
      student a personal sense of accomplishment, self-awareness, command of the
      material and technology. This helps build the interest and confidence necessary
      to excel in STEM and throughout life. Finally the introduction and use of
      relevant technologies at every stage of the education process ensures technical
      familiarity and a broad knowledge base needed for work in STEM based fields.
      Biomedical engineering education strives to cultivate broad technical adeptness,
      creativity, interdisciplinary thought, and an ability to form deep conceptual
      understanding of complex systems. The FabLab platform is well designed to enhance
      biomedical engineering education. 

PMID- 25570332
TI  - Automatic gesture analysis using constant affine velocity.
AB  - Hand human gesture recognition has been an important research topic widely
      studied around the world, as this field offers the ability to identify,
      recognize, and analyze human gestures in order to control devices or to interact
      with computer interfaces. In particular, in medical training, this approach is an
      important tool that can be used to obtain an objective evaluation of a procedure
      performance. In this paper, some obstetrical gestures, acquired by a forceps,
      were studied with the hypothesis that, as the scribbling and drawing movements,
      they obey the one-sixth power law, an empirical relationship which connects path
      curvature, torsion, and euclidean velocity. Our results show that obstetrical
      gestures have a constant affine velocity, which is different for each type of
      gesture and based on this idea this quantity is proposed as an appropriate
      classification feature in the hand human gesture recognition field. 

PMID- 25570333
TI  - Chair rise transfer detection and analysis using a pendant sensor: an algorithm
      for fall risk assessment in older people.
AB  - Falls result in substantial disability, morbidity, and mortality among older
      people. Early detection of fall risks and timely intervention can prevent falls
      and injuries due to falls. Simple field tests, such as repeated chair rise, are
      used in clinical assessment of fall risks in older people. Development of on-body
      sensors introduces potential beneficial alternatives for traditional clinical
      methods. In this article, we present a pendant sensor based chair rise detection
      and analysis algorithm for fall risk assessment in older people. The recall and
      the precision of the transfer detection were 85% and 87% in standard protocol,
      and 61% and 89% in daily life activities. Estimation errors of chair rise
      performance indicators: duration, maximum acceleration, peak power and maximum
      jerk were tested in over 800 transfers. Median estimation error in transfer peak
      power ranged from 1.9% to 4.6% in various tests. Among all the performance
      indicators, maximum acceleration had the lowest median estimation error of 0% and
      duration had the highest median estimation error of 24% over all tests. The
      developed algorithm might be feasible for continuous fall risk assessment in
      older people. 

PMID- 25570334
TI  - Classification of salivary based NS1 from Raman Spectroscopy with support vector
      machine.
AB  - Non-Structural Protein 1 (NS1) antigen has been recognized as a biomarker for
      diagnosis of flavivirus viral infections at early stage. Surface Enhanced Raman
      Spectroscopy (SERS) is an optical technique capable of detecting up to a single
      molecule. Our previous work has established the Raman fingerprint of NS1 with
      gold as substrate. Our current study aims to classify NS1 infected saliva samples
      from healthy samples, a first ever attempt. Saliva samples from healthy subjects,
      NS1 protein and NS1-saliva mixture samples were analyzed using SERS. The SERS
      spectra were then pre-processed prior to classification with support vector
      machine (SVM). NS1-saliva mixture at concentration of 10ppm, 50ppm and 100ppm
      were examined. Performance of SVM classifier with linear, polynomial and radial
      basis function (RBF) kernels were compared, in term of accuracy, sensitivity, and
      specificity. From the results, it can be concluded that SVM classifier is able to
      classify the samples into NS1 infected samples and normal saliva samples. Of the
      three kernels, performance in using polynomial and RBF kernel is found surpassing
      the linear kernel. The best performance is attained with RBF kernel with accuracy
      of [97.1% 93.4% 81.5%] for 100ppm, 50ppm and 10ppm respectively. 

PMID- 25570335
TI  - Characterizing touch using pressure data and auto regressive models.
AB  - Palpation plays a critical role in medical physical exams. Despite the wide range
      of exams, there are several reproducible and subconscious sets of maneuvers that
      are common to examination by palpation. Previous studies by our group
      demonstrated the use of manikins and pressure sensors for measuring and
      quantifying how physicians palpate during different physical exams. In this study
      we develop mathematical models that describe some of these common maneuvers.
      Dynamic pressure data was measured using a simplified testbed and different
      autoregressive models were used to describe the motion of interest. The
      frequency, direction and type of motion used were identified from the models. We
      believe these models can a provide better understanding of how humans explore
      objects in general and more specifically give insights to understand medical
      physical exams. 

PMID- 25570336
TI  - Cloud-scale genomic signals processing classification analysis for gene
      expression microarray data.
AB  - As microarray data available to scientists continues to increase in size and
      complexity, it has become overwhelmingly important to find multiple ways to bring
      inference though analysis of DNA/mRNA sequence data that is useful to scientists.
      Though there have been many attempts to elucidate the issue of bringing forth
      biological inference by means of wavelet preprocessing and classification, there
      has not been a research effort that focuses on a cloud-scale classification
      analysis of microarray data using Wavelet thresholding in a Cloud environment to
      identify significantly expressed features. This paper proposes a novel
      methodology that uses Wavelet based Denoising to initialize a threshold for
      determination of significantly expressed genes for classification. Additionally,
      this research was implemented and encompassed within cloud-based distributed
      processing environment. The utilization of Cloud computing and Wavelet
      thresholding was used for the classification 14 tumor classes from the Global
      Cancer Map (GCM). The results proved to be more accurate than using a predefined
      p-value for differential expression classification. This novel methodology
      analyzed Wavelet based threshold features of gene expression in a Cloud
      environment, furthermore classifying the expression of samples by analyzing gene
      patterns, which inform us of biological processes. Moreover, enabling researchers
      to face the present and forthcoming challenges that may arise in the analysis of
      data in functional genomics of large microarray datasets. 

PMID- 25570337
TI  - Spatial filter adaptation based on the divergence framework for motor imagery EEG
      classification.
AB  - To address the nonstationarity issue in EEG-based brain computer interface (BCI),
      the computational model trained using the training data needs to adapt to the
      data from the test sessions. In this paper, we propose a novel adaptation
      approach based on the divergence framework. Cross-session changes can be taken
      into consideration by searching the discriminative subspaces for test data on the
      manifold of orthogonal matrices in a semi-supervised manner. Subsequently, the
      feature space becomes more consistent across sessions and classifiers performance
      can be enhanced. Experimental results show that the proposed adaptation method
      yields improvements in classification performance. 

PMID- 25570338
TI  - Separate estimation of long- and short-term systolic blood pressure variability
      from photoplethysmograph.
AB  - This paper proposed a method to monitor systolic blood pressure (BP) variability
      without using a cuff during the daytime. In this method, BP variability of long
      term and short-term were separated and estimated respectively from features of
      phoplethysmograph (PPG) through the use of a frequency filter. Then, total
      variability was obtained from the combination of long-term and short-term. BP by
      using a cuff (ground truth) and PPG of nine healthy young subjects were measured
      during the daytime; then BP variability was estimated from PPG to verify the
      validity of our method. As a result, the correlation coefficients between
      measured BP variability and estimated BP variability was improved from r = 0.35
      in previous method to r = 0.41 in proposed method. In particular, the estimation
      results in short-term BP variability showed good accuracy (r = 0.67). This method
      of estimating BP variability has the potential to be a simple and continuous BP
      monitoring system during the daytime. 

PMID- 25570339
TI  - Scoring consensus of multiple ECG annotators by optimal sequence alignment.
AB  - Development of ECG delineation algorithms has been an area of intense research in
      the field of computational cardiology for the past few decades. However, devising
      evaluation techniques for scoring and/or merging the results of such algorithms,
      both in the presence or absence of gold standards, still remains as a challenge.
      This is mainly due to existence of missed or erroneous determination of fiducial
      points in the results of different annotation algorithms. The discrepancy between
      different annotators increases when the reference signal includes arrhythmias or
      significant noise and its morphology deviates from a clean ECG signal. In this
      work, we propose a new approach to evaluate and compare the results of different
      annotators under such conditions. Specifically, we use sequence alignment
      techniques similar to those used in bioinformatics for the alignment of gene
      sequences. Our approach is based on dynamic programming where adequate mismatch
      penalties, depending on the type of the fiducial point and the underlying signal,
      are defined to optimally align the annotation sequences. We also discuss how to
      extend the algorithm for more than two sequences by using suitable data
      structures to align multiple annotation sequences with each other. Once the
      sequences are aligned, different heuristics are devised to evaluate the
      performance against a gold standard annotation, or to merge the results of
      multiple annotations when no gold standard exists. 

PMID- 25570340
TI  - Statistical and nonlinear analysis of oximetry from respiratory polygraphy to
      assist in the diagnosis of Sleep Apnea in children.
AB  - Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) is a sleep related breathing
      disorder that has important consequences in the health and development of infants
      and young children. To enhance the early detection of OSAHS, we propose a
      methodology based on automated analysis of nocturnal blood oxygen saturation
      (SpO(2)) from respiratory polygraphy (RP) at home. A database composed of 50
      SpO(2) recordings was analyzed. Three signal processing stages were carried out:
      (i) feature extraction, where statistical features and nonlinear measures were
      computed and combined with conventional oximetric indexes, (ii) feature selection
      using genetic algorithms (GAs), and (iii) feature classification through logistic
      regression (LR). Leave-one-out cross-validation (loo-cv) was applied to assess
      diagnostic performance. The proposed method reached 80.8% sensitivity, 79.2%
      specificity, 80.0% accuracy and 0.93 area under the ROC curve (AROC), which
      improved the performance of single conventional indexes. Our results suggest that
      automated analysis of SpO(2) recordings from at-home RP provides essential and
      complementary information to assist in OSAHS diagnosis in children.

PMID- 25570341
TI  - ECG reconstruction based on the injection of a multi-frequency signal in
      capacitive measurement systems.
AB  - Many healthcare and lifestyle applications could benefit from capacitive
      measurement systems for unobtrusive ECG monitoring. However, a key technical
      challenge remains: the susceptibility of such systems to motion artifacts and
      common-mode interferences. With this in mind, we developed a novel method to
      reduce various types of artifacts present in capacitive ECG measurement systems.
      The objective is to perform ECG reconstruction and channel balancing in an
      automated and continuous manner. The proposed method consists of a) modeling the
      measurement system; b) specifically parameterizing the reconstruction equation;
      and c) adaptively estimating the parameters. A multi-frequency injection signal
      serves to estimate and track the variations of the different parameters of the
      reconstruction equation. A preliminary investigation on the validity of the
      method has been performed in both simulation and lab environment: the method
      shows benefits in terms of common-mode interference and motion artifact
      reduction, resulting in improved R-peak detection. 

PMID- 25570342
TI  - Multivariate analysis based on linear and non-linear FHR parameters for the
      identification of IUGR fetuses.
AB  - Fetal Heart Rate (FHR) monitoring represents a powerful tool for checking the
      arousal of pathological fetal conditions during pregnancy. This paper proposes a
      multivariate approach for the discrimination of Normal and Intra Uterine Growth
      Restricted (IUGR) fetuses based on a small set of parameters computed on the FHR
      signal. We collected FHR recordings in a population of 120 fetuses (60 normals
      and 60 IUGRs) at approximately the same gestational week through a standard CTG
      non-stress test. A set of 8 linear and non-linear indices were selected and
      computed on each recording, on the basis of their "stand-alone" discriminative
      properties, demonstrated in previous studies. By using the Orange(r) data mining
      suite we checked various multivariate discrimination models. The results show
      that a Logistic Regression performed on a limited set of only 4 parameters can
      reach 92.5% accuracy in the correct identification of fetuses, with 93%
      sensitivity and 91.5% specificity. 

PMID- 25570343
TI  - Improved signal quality indication for photoplethysmographic signals
      incorporating motion artifact detection.
AB  - Wearable monitoring systems have gained tremendous popularity in the health-care
      industry, opening new possibilities in diagnostic routines and medical
      treatments. Numerous hardware systems have been presented since, which allow for
      continuous acquisition of various biosignals like the ECG, PPG, EMG or EEG and
      which are suited for ambulatory settings. Unfortunately, these flexible systems
      are liable to motion artifacts and especially photoplethysmographic signals are
      seriously distorted when the patient is not at rest. A lot of work has been done
      to reduce artifacts and noise, ranging from simple filtering methods to very
      complex statistical approaches. With regard to the PPG, certain quality indices
      have been proposed to evaluate the signal conditions. As movements are the
      primary source of signal disturbances, the relation between the output of a
      signal quality estimator and acceleration data captured directly on the PPG
      sensor is focused in this work. It will be shown that typical motions can be
      detected on-line, thereby providing additional information which will
      significantly improve signal quality assessments. 

PMID- 25570344
TI  - Comparison of feature and classifier algorithms for online automatic sleep
      staging based on a single EEG signal.
AB  - Automatic sleep staging on an online basis has recently emerged as a research
      topic motivated by fundamental sleep research. The aim of this paper is to find
      optimal signal processing methods and machine learning algorithms to achieve
      online sleep staging on the basis of a single EEG signal. The classification
      performance obtained using six different EEG signals and various signal
      processing feature sets is compared using the kappa statistic which has very
      recently become popular in sleep staging research. A variable duration of the EEG
      segment (or epoch) to decide on the sleep stage is also analyzed. Spectral
      domain, time-domain, linear, and nonlinear features are compared in terms of
      performance and two types of machine learning approaches (random forests and
      support vector machines) are assessed. We have determined that frontal EEG
      signals, with spectral linear features, epoch durations between 18 and 30
      seconds, and a random forest classifier lead to optimal classification
      performance while ensuring real-time online operation. 

PMID- 25570345
TI  - Automated detection and correction of eye blink and muscular artefacts in EEG
      signal for analysis of Autism Spectrum Disorder.
AB  - Autism Spectrum Disorder (ASD) is a neural development disorder affecting the
      information processing capability of the brain by altering how nerve cells and
      their synapses interconnect and organize. Electroencephalograph or EEG signals
      records the electrical activity of the brain from the scalp which can be utilized
      to identify and investigate the brain wave pattern which are specific to
      individuals with ASD. Therefore, the analysis of ASD can be done by scrutinizing
      the specific bands (Theta, Mu and Beta) of the EEG signal. However, EEG signals
      are mainly contaminated by Ocular (Eye-blink) and Myogenic artefacts which pose
      problems in EEG interpretation. In this paper an automated real-time method for
      detection and removal of Ocular and Myogenic artefacts for multichannel EEG
      signal is proposed which would enhance the diagnostic accuracy. The proposed
      methodology has been validated against 20 subjects from Caltech, Physionet,
      Swartz Center for Computational Neuroscience and the computed average correlation
      and regression are 0.7574 and 0.6992 respectively. 

PMID- 25570346
TI  - A multi-dimensional Hidden Markov Model approach to automated identification of
      fetal cardiac valve motion.
AB  - Fetal cardiac assessment techniques are aimed to identify fetuses at risk of
      intrauterine compromise or death. Evaluation of the electromechanical coupling as
      a fundamental part of the fetal heart physiology, provides valuable information
      about the fetal wellbeing during pregnancy. It is based on the opening and
      closing time of the cardiac valves and the onset of the QRS complex of the fetal
      electrocardiogram (fECG). The focus of this paper is on the automated
      identification of the fetal cardiac valve opening and closing from Doppler
      Ultrasound signal and fECG as a reference. To this aim a novel combination of
      Emprical Mode Decomposition (EMD) and multi-dimensional Hidden Markov Models (MD
      HMM) was employed which provided beat-to-beat estimation of cardiac valve event
      timings with improved precision (82.9%) compared to the one dimensional HMM
      (77.4%) and hybrid HMM-Support Vector Machine (SVM) (79.8%) approaches. 

PMID- 25570347
TI  - Modeling quasi-periodic signals by a non-parametric model: application on fetal
      ECG extraction.
AB  - Quasi-periodic signals can be modeled by their second order statistics as
      Gaussian process. This work presents a non-parametric method to model such
      signals. ECG, as a quasi-periodic signal, can also be modeled by such method
      which can help to extract the fetal ECG from the maternal ECG signal, using a
      single source abdominal channel. The prior information on the signal shape, and
      on the maternal and fetal RR interval, helps to better estimate the parameters
      while applying the Bayesian principles. The values of the parameters of the
      method, among which the R-peak instants, are accurately estimated using the
      Metropolis-Hastings algorithm. This estimation provides very precise values for
      the R-peaks, so that they can be located even between the existing time samples. 

PMID- 25570348
TI  - Superiority of high frequency hypoxic ischemic EEG signals of fetal sheep for
      sharp wave detection using Wavelet-Type 2 Fuzzy classifiers.
AB  - There is approximately a 6-8 hour window that exists from when a hypoxic-ischemic
      insult occurs, in utero, before significant irreversible brain injury occurs in
      new born infants. The focus of our work is to determine through the
      electroencephalogram (EEG) if such a hypoxic-ischemic insult has occurred such
      that neuro-protective treatment can be sought within this period. At present,
      there are no defined biomarkers in the EEG that are currently being used to help
      classify if a hypoxic ischemia insult has occurred. However, micro-scale
      transients in the form of spikes, sharps and slow waves exists that could provide
      precursory information whether a hypoxic-ischemic insult has occurred or not. In
      our previous studies we have successfully automatically identified spikes with
      high sensitivity and selectivity in the conventional 64Hz sampled EEG. This paper
      details the significant advantage that can be obtained in using high frequency
      1024Hz sampled EEG for sharp wave detection over the typically employed 64Hz
      sampled EEG. This advantage is amplified when a combination of wavelet Type-2
      Fuzzy Logic System (WT-Type-2-FLS) classifiers are used to identify the sharp
      wave transients. By applying WT-Type-2-FLS to the 1024Hz EEG record and to the
      same down-sampled 64Hz EEG record we demonstrate, how the sharp wave transients
      detection increases significantly for high resolution 1024Hz EEG over 64Hz EEG.
      The WT-Type-2-FLS algorithm performance was assessed over 3 standardised time
      periods within the first 8 hours, post occlusion of a fetal sheep, in utero.
      1024Hz EEG results demonstrate the algorithm detected sharps with overall
      performance rates of 85%, 92%, and 87% in the Early/Mid and Late-latent phases of
      injury, respectively as compared to 25%, 55% and 31% in the 64Hz EEG. These
      results demonstrate the power of Wavelet Type-2 Fuzzy Logic System at detecting
      sharp waves in 1024Hz EEG and suggest that there should be a movement toward
      recording high frequency EEG for analysis of hypoxic ischemic micro-scale
      transients that does not occur at present. 

PMID- 25570349
TI  - Automated prediction of the apnea-hypopnea index using a wireless patch sensor.
AB  - Polysomnography (PSG) is the gold standard that manually quantifies the apnea
      hypopnea index (AHI) to assess the severity of sleep apnea syndrome (SAS). This
      study presents an algorithm that automatically estimates the AHI value using a
      disposable HealthPatch(TM) sensor. Volunteers (n=53, AHI: 0.1-85.8) participated
      in an overnight PSG study with patch sensors attached to their chest at three
      specified locations and data were wirelessly acquired. Features were computed for
      150-second epochs of patch sensor data using analyses of heart rate variability,
      respiratory signals, posture and movements. Linear Support Vector Machine
      classifier was trained to detect the presence/absence of apnea/hypopnea events
      for each epoch. The number of epochs identified with events was subsequently
      mapped to AHI values using quadratic regression analysis. The classifier and
      regression models were optimized to minimize the mean-square error of AHI based
      on leave-one-out cross-validation. Comparison of predicted and reference AHI
      values resulted in linear correlation coefficients of 0.87, 0.88 and 0.92 for the
      three locations, respectively. The predicted AHI values were subsequently used to
      classify the control-to-mild apnea group (AHI<;15) and moderate-to-severe apnea
      (AHI>=15) with an accuracy (95% confidence intervals) of 89.4% (77.4-95.4%),
      85.0% (70.9-92.9%), and 82.9% (67.3-91.9%) for the three locations, respectively.
      Overnight physiological monitoring using a wireless patch sensor provides an
      accurate estimate of AHI. 

PMID- 25570350
TI  - Efficient PET-CT image retrieval using graphs embedded into a vector space.
AB  - Combined positron emission tomography and computed tomography (PET-CT) produces
      functional data (from PET) in relation to anatomical context (from CT) and it has
      made a major contribution to improved cancer diagnosis, tumour localisation, and
      staging. The ability to retrieve PET-CT images from large archives has potential
      applications in diagnosis, education, and research. PET-CT image retrieval
      requires the consideration of modality-specific 3D image features and spatial
      contextual relationships between features in both modalities. Graph-based
      retrieval methods have recently been applied to represent contextual
      relationships during PET-CT image retrieval. However, accurate methods are
      computationally complex, often requiring offline processing, and are unable to
      retrieve images at interactive rates. In this paper, we propose a method for PET
      CT image retrieval using a vector space embedding of graph descriptors. Our
      method defines the vector space in terms of the distance between a graph
      representing a PET-CT image and a set of fixed-sized prototype graphs; each
      vector component measures the dissimilarity of the graph and a prototype. Our
      evaluation shows that our method is significantly faster (~800* speedup, p <;
      0.05) than retrieval using the graph-edit distance while maintaining comparable
      precision (5% difference, p > 0.05). 

PMID- 25570351
TI  - A framework using multimodal imaging for longitudinal monitoring of patients in
      neuro-oncology. Application to a SPECT/MRI study.
AB  - This paper proposes a framework to assess the potential value of 99mTc Sestamibi
      SPECT in addition to Gadolinium-enhanced MRI for the monitoring of patients with
      high grade gliomas under antiangiogenic treatment. It includes: 1) multimodal and
      monomodal high precision registration steps achieved thanks to a registration
      strategy which selects the best method among several ones for each dataset, 2)
      tumor segmentation steps dedicated to each modality and 3) a tumor comparison
      step which consists in the computation of some global (volume, intensity) and
      local (matching and mismatching) quantitative indices to analyze the tumor using
      different imaging modalities and at different times during the treatment. Each
      step is checked via 2D and 3D visualization. This framework was applied to a
      database of fifteen patients. For all patients, except one, the tumor volumes
      decrease globally and locally. Furthermore, a high correlation (r=0.77) was
      observed between MRI and Sestamibi tumor volumes. Finally, local indices show
      some possible mismatches between MRI Gadolinium uptake and Sestamibi uptake,
      which need to be further investigated. 

PMID- 25570352
TI  - QAV-PET: Quantitative Analysis and Visualization of PET images.
AB  - Open source software advances research and allows for more application specific
      tuning in a very feasible and efficient manner. Chief among the open source
      platforms is the MATLAB programming environment which is very commonly used in
      research settings especially in the field of medical imaging. Although many
      scientists use MATLAB for analysis, there remains a significant lack of open
      source software platforms which allow for both the analysis and visualization of
      pathological regions within fused multi-modal medical images. There is a clear
      need for a MATLAB based software which allows for anatomical (i.e. CT or MRI) and
      functional (i.e. PET) joint visualization and quantification in an intuitive and
      efficient way. In particular, this software should focus on PET imaging which is
      being more widely used for small animal studies. We present here the structure,
      features, and potential applications of an open source software for the
      Quantitative Analysis and Visualization of PET Images (QAV-PET). 

PMID- 25570353
TI  - Classification of thresholded regions based on selective use of PET, CT and PET
      CT image features.
AB  - Fluorodeoxyglucose positron emission tomography - computed tomography (FDG PET
      CT) is the preferred image modality for lymphoma diagnosis. Sites of disease
      generally appear as foci of increased FDG uptake. Thresholding methods are often
      applied to robustly separate these regions. However, its main limitation is that
      it also includes sites of FDG excretion and physiological FDG uptake regions,
      which we define as FEPU - sites of FEPU include the bladder, renal, papillae,
      ureters, brain, heart and brown fat. FEPU can make image interpretation
      problematic. The ability to identify and label FEPU sites and separate them from
      abnormal regions is an important process that could improve image interpretation.
      We propose a new method to automatically separate and label FEPU sites from the
      thresholded PET images. Our method is based on the selective use of features
      extracted from data types comprising of PET, CT and PET-CT. Our FEPU
      classification of 43 clinical lymphoma patient studies revealed higher accuracy
      when compared to non-selective image features. 

PMID- 25570354
TI  - Low dose PET reconstruction with total variation regularization.
AB  - Low dose positron emission tomography(PET) reconstruction remains a challenging
      issue for statistical PET reconstruction methods due to the low SNR of data. Due
      to the ill-conditioning of image reconstruction, proper prior knowledge should be
      incorporated to constrain the reconstruction. Since PET images are piecewise
      smoothing, we propose the total variational (TV) minimization based algorithm for
      low dose PET imaging. The fundamental power of this strategy rests with the edge
      locations of important image features tend to be preserved thanks to TV
      regularization. In addition, a new computational method have been employed with
      improved computational speed and robustness. Experimental results on Monte Carlo
      simulations demonstrate its superior performance. 

PMID- 25570355
TI  - Exploitation of realistic computational anthropomorphic phantoms for the
      optimization of nuclear imaging acquisition and processing protocols.
AB  - Monte Carlo (MC) simulations play a crucial role in nuclear medical imaging since
      they can provide the ground truth for clinical acquisitions, by integrating and
      quantifing all physical parameters that affect image quality. The last decade a
      number of realistic computational anthropomorphic models have been developed to
      serve imaging, as well as other biomedical engineering applications. The
      combination of MC techniques with realistic computational phantoms can provide a
      powerful tool for pre and post processing in imaging, data analysis and
      dosimetry. This work aims to create a global database for simulated Single Photon
      Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) exams
      and the methodology, as well as the first elements are presented. Simulations are
      performed using the well validated GATE opensource toolkit, standard
      anthropomorphic phantoms and activity distribution of various
      radiopharmaceuticals, derived from literature. The resulting images, projections
      and sinograms of each study are provided in the database and can be further
      exploited to evaluate processing and reconstruction algorithms. Patient studies
      using different characteristics are included in the database and different
      computational phantoms were tested for the same acquisitions. These include the
      XCAT, Zubal and the Virtual Family, which some of which are used for the first
      time in nuclear imaging. The created database will be freely available and our
      current work is towards its extension by simulating additional clinical
      pathologies. 

PMID- 25570356
TI  - An automated dental caries detection and scoring system for optical images of
      tooth occlusal surface.
AB  - Dental caries are one of the most prevalent chronic diseases. The management of
      dental caries demands detection of carious lesions at early stages. This study
      aims to design an automated system to detect and score caries lesions based on
      optical images of the occlusal tooth surface according to the International
      Caries Detection and Assessment System (ICDAS) guidelines. The system detects the
      tooth boundaries and irregular regions, and extracts 77 features from each image.
      These features include statistical measures of color space, grayscale image, as
      well as Wavelet Transform and Fourier Transform based features. Used in this
      study were 88 occlusal surface photographs of extracted teeth examined and scored
      by ICDAS experts. Seven ICDAS codes which show the different stages in caries
      development were collapsed into three classes: score 0, scores 1 and 2, and
      scores 3 to 6. The system shows accuracy of 86.3%, specificity of 91.7%, and
      sensitivity of 83.0% in ten-fold cross validation in classification of the tooth
      images. While the system needs further improvement and validation using larger
      datasets, it presents promising potential for clinical diagnostics with high
      accuracy and minimal cost. This is a notable advantage over existing systems
      requiring expensive imaging and external hardware. 

PMID- 25570357
TI  - Occlusal caries detection using random walker algorithm: a graph approach.
AB  - The aim of this work is to present a modification of the Random Walker algorithm
      for the segmentation of occlusal caries from photographic color images. The
      modification improves the detection and time execution performance of the
      classical Random Walker algorithm and also deals with the limitations and
      difficulties that the specific type of images impose to the algorithm. The
      proposed modification consists of eight steps: 1) definition of the seed points,
      2) conversion of the image to gray scale, 3) application of watershed
      transformation, 4) computation of the centroid of each region, 5) construction of
      the graph, 6) application of the Random Walker algorithm, 7) smoothing and
      extraction of the perimeter of the regions of interest and 8) overlay of the
      results. The algorithm was evaluated using a set of 96 images where 339 areas of
      interest were manually segmented by an expert. The obtained segmentation accuracy
      is 93%. 

PMID- 25570358
TI  - Evaluation of performance metrics for histopathological image classifier
      optimization.
AB  - Clinical decision support systems use image processing and machine learning
      methods to objectively predict cancer in histopathological images. Integral to
      the development of machine learning classifiers is the ability to generalize from
      training data to unseen future data. A classification model's ability to
      accurately predict class label for new unseen data is measured by performance
      metrics, which also informs the classifier model selection process. Based on our
      research, commonly used metrics in literature (such as accuracy, ROC curve) do
      not accurately reflect the trained model's robustness. To the best of our
      knowledge, no research has been conducted to quantitatively compare performance
      metrics in the context of cancer prediction in histopathological images. In this
      paper, we evaluate various performance metrics and show that the Lift metric has
      the highest correlation between internal and external validation sets of a nested
      cross validation pipeline (R(2) = 0.57). Thus, we demonstrate that the Lift
      metric best generalizes classifier performance among the 23 metrics that were
      evaluated. Using the lift metric, we develop a classifier with a
      misclassification rate of 0.25 (4-class classifier) for data that the model was
      not trained on (external validation). 

PMID- 25570359
TI  - A feature selection based framework for histology image classification using
      global and local heterogeneity quantification.
AB  - Biopsy remains the gold standard for the diagnosis of chronic liver diseases.
      However, the concordance between readers is subject to variability causing an
      increasing need of objective tissue description methods. A complete framework has
      been implemented to analyze histological images from any kind of tissue. Based on
      the feature selection approach, it computes the most relevant subset of
      descriptors in terms of classification from a wide initial list of local and
      global descriptors. In comparison with equivalent methods, this implementation is
      able to find lists of descriptors which are significantly shorter for an
      equivalent accuracy and furthermore it enables the classification of slides using
      combinations of global and local measurements. The results have pointed that it
      could reach an accuracy of 82.8% in a human liver fibrosis grading approach by
      selecting 6 descriptors from an initial set of 258 global and local descriptors. 

PMID- 25570360
TI  - Longitudinal FDG-PET features for the classification of Alzheimer's disease.
AB  - The majority of existing computer-aided diagnosis (CAD) schemes for Alzheimer's
      disease (AD) rely on the analysis of biomarkers at a single time-point, ignoring
      the progressive nature of the disorder. Recently, a method was proposed by Gray
      et al. [1] for the multi-region analysis of longitudinal fluorodeoxyglucose
      positron emission tomography (FDG-PET) images which reported classification
      improvements by using regional signal intensities combined with regional change
      over a 12 month period. In this paper we extend the approach proposed in [1] to
      the analysis of the entire brain pattern. Compared to [1], our method uses voxel
      wise differences and avoids segmentation of the images into regions of interest.
      For our study, FDG-PET scans at the baseline and at 12-month follow-up of
      cognitively normal (CN), mild cognitive impairment (MCI) and AD subjects were
      retrieved from the Alzheimer's disease neuroimaging initiative (ADNI) database.
      For both AD and MCI identification, the best classification results were achieved
      by combining cross-sectional and longitudinal information rather than using only
      the cross-sectional data. Furthermore, the longitudinal voxel-based analysis
      outperformed multi-region analysis. 

PMID- 25570361
TI  - Atrophy analysis of corpus callosum in Alzheimer brain MR images using
      anisotropic diffusion filtering and level sets.
AB  - In this work, an attempt has been made to analyze the atrophy of Corpus Callosum
      (CC) in Alzheimer brain magnetic resonance images using anisotropic diffusion
      filtering and modified distance regularized level set method. Anisotropic
      diffusion filtering is used as preprocessing to obtain the edge map. The modified
      distance regularized level set method is employed to segment CC using this edge
      map. Geometric features are extracted from the segmented CC and are analyzed.
      Results show that anisotropic diffusion filtering is able to extract the edge map
      with high contrast and continuous boundaries. Modified distance regularized level
      set method could perform the segmentation of CC in both normal and Alzheimer
      images. The extracted geometric features such as minor axis, Euler number and
      solidity are able to demarcate the Alzheimer subjects from the control normals.
      As atrophy of CC is closely associated with the pathology, this study seems to be
      clinically useful. 

PMID- 25570362
TI  - Is there opportunity for automated decision-support and closed-loop control in
      ICU patients receiving vasopressor infusion?
AB  - Vasopressors are administered to critically ill patients suffering from a body
      wide reduction in blood circulation. In theory, if the vasopressor infusion is
      either too high or too low, it could be harmful to the patient. In a
      retrospective analysis, we investigated the degree to which today's intensive
      care unit (ICU) patients receive appropriate vasopressor therapy, in terms of how
      often the mean arterial pressure (MAP) was kept within a normative range. Using
      the MIMIC II database, we studied patients with minute-by-minute MAP data,
      sourced from the bedside monitor, who were receiving vasopressor therapy. For
      each record, we identified MAP samples that were out-of-range, i.e., MAP <; 60
      mmHg or MAP > 100 mmHg, and grouped these into out-of-range episodes. Each out-of
      range episode was categorized as either transient (<; 15 min) or sustained (>= 15
      min). Out of the 224 ICU stays, we identified 152 ICU stays (68% of ICU stays)
      with at least one sustained MAP out-of-range episode. In that subset, MAP was
      frequently out-of-range (out-of-range 18.4% of the time) due to a combination of
      sustained episodes of hypotension and hypertension. Compared with all ICU stays,
      those stays with sustained out-of-range events did not demonstrate an increased
      MAP variability per hour. It is possible that the out-of-range events resulted
      from insufficient dose-adjustment. Technologies that might continuously optimize
      vasopressor dosing throughout the patient's stay and thereby minimize these
      abnormal cardiovascular states may be worthy of further study. 

PMID- 25570363
TI  - Magnetic plethysmograph transducers for local blood pulse wave velocity
      measurement.
AB  - We present the design of magnetic plethysmograph (MPG) transducers for detection
      of blood pulse waveform and evaluation of local pulse wave velocity (PWV), for
      potential use in cuffless blood pressure (BP) monitoring. The sensors utilize a
      Hall effect magnetic field sensor to capture the blood pulse waveform. A strap
      based design is performed to enable reliable capture of large number of cardiac
      cycles with relative ease. The ability of the transducer to consistently detect
      the blood pulse is verified by in-vivo trials on few volunteers. A duality of
      such transducers is utilized to capture the local PWV at the carotid artery. The
      pulse transit time (PTT) between the two detected pulse waveforms, measured along
      a small section of the carotid artery, was evaluated using automated algorithms
      to ensure consistency of measurements. The correlation between the measured
      values of local PWV and BP was also investigated. The developed transducers
      provide a reliable, easy modality for detecting pulse waveform on superficial
      arteries. Such transducers, used for measurement of local PWV, could potentially
      be utilized for cuffless, continuous evaluation of BP at various superficial
      arterial sites. 

PMID- 25570364
TI  - An improved method for detection of carotid walls in ARTSENS.
AB  - We have been developing a fully automated ultrasound based imageless system to
      facilitate mass screening of patients for future risk of cardiovascular diseases.
      The device shall enable a general medical practitioner to non-invasively measure
      the local arterial stiffness of common carotid artery (CCA) and has been
      acronymed ARTerial Stiffness Evaluation for Non-invasive Screening (ARTSENSTM).
      Complete automation of the system requires providing assistance in placement of
      probe over the CCA location and automatic identification of approximate location
      of proximal wall (PW) and distal wall (DW) of the CCA. In this paper we propose a
      method based on temporal motion of PW and DW over successive A-Mode frames to
      locate the CCA. We evaluated the performance of the algorithm with data obtained
      from CCA of 30 subjects. It could correctly identify the CCA in more than 70 % of
      trials. We also propose a method for preprocessing the frames by using the
      transmitted pulse wavelet. This improved the detection rate significantly. False
      positives were always less than 6% of total detections. 

PMID- 25570365
TI  - Model-based oscillometric blood pressure measurement: preliminary validation in
      humans.
AB  - We conceived new oscillometric blood pressure (BP) estimation methods based on
      physical modeling. The crux of these methods is to simultaneously estimate the
      arterial stiffness and BP of the patient from a standard oscillometric waveform.
      Hence, in contrast to previous methods, the BP estimation is specific to the
      patient at the time of measurement and is robust against arterial stiffening. We
      conducted initial testing of one of the methods against invasive reference
      brachial BP measurements in eight cardiac catheterization patients before and
      after nitroglycerin infusions. The method achieved systolic, diastolic and mean
      BP root-mean-squared-errors of 7.2, 7.6 and 6.7 mmHg. These errors were, on
      average, 40% lower than an existing high-end method. 

PMID- 25570366
TI  - Investigation of Pulse Transit Times utilizing multisite reflectance
      photoplethysmography under conditions of artificially induced peripheral
      vasoconstriction.
AB  - Pulse Transit Time (PTT) is the time it takes for an arterial pulsation to travel
      from the heart to a peripheral site. In recent times, PTT has been advocated as a
      marker for assessing increased vascular resistance. However, the reliability of
      PTT as a marker for cardiovascular risks and its inverse relation to beat-to-beat
      blood pressure is still being investigated. In order to validate the technique as
      a reliable marker of vascular resistance, PTT measurements were made using
      photoplethysmographic (PPG) signals obtained from multiple measurement sites in
      12 healthy volunteers undergoing right hand immersion in ice water for 30 secs.
      PTT measurements were made from the ear canal (EC), the left (LIF) and right
      index fingers (RIF) using custom made photoplethysmographic probes. Activation of
      the sympathetic nervous system during the ice water immersion caused an increase
      in vascular resistance, which is associated with an increase in mean arterial
      pressure and a decrease in PTT in all measurement sites. However, the change in
      PTT was much larger in the RIF when compared to the LIF and the EC. This
      demonstrates the cerebral flow autoregulation and the profound peripheral
      vasoconstriction seen in the right hand. After the ice immersion period, the mean
      PTT measured from the EC returned to baseline, whereas the LIF PTT exceeded
      baseline values. This is due to the local vasodilation resulted from the
      activation of a thermoregulation mechanism. 

PMID- 25570367
TI  - Numerical assessment of the stiffness index.
AB  - Elevated systemic vascular stiffness is associated with increased risk of
      cardiovascular disease. It has been suggested that the time difference between
      the two characteristic peaks of the digital volume pulse (DVP) measured at the
      finger using photoplethysmography is related to the stiffness of the arterial
      tree, and inversely proportional to the stiffness index (SI). However, the
      precise physical meaning of the SI and its relation to aortic pulse wave velocity
      (aPWV) is yet to be ascertained. In this study we investigated numerically the
      effect of changes in arterial wall stiffness, peripheral resistances, peripheral
      compliances or peripheral wave reflections on the SI and aPWV. The SI was
      calculated from the digital area waveform simulated using a nonlinear one
      dimensional model of pulse wave propagation in a 75-artery network, which
      includes the larger arteries of the hand. Our results show that aPWV is affected
      by changes in aortic stiffness, but the SI is primarily affected by changes in
      the stiffness of all conduit vessels. Thus, the SI is not a direct substitute for
      aPWV. Moreover, our results suggest that peripheral reflections in the upper body
      delay the time of arrival of the first peak in the DVP. The second peak is
      predominantly caused by the impedance mismatch within the 75 arterial segments,
      rather than by peripheral reflections. 

PMID- 25570368
TI  - Chronic sensory-motor activity in behaving animals using regenerative multi
      electrode interfaces.
AB  - Regenerative peripheral nerve interfaces have been proposed as viable
      alternatives for the natural control and feel of robotic prosthetic limbs. We
      have developed a Regenerative Multi-electrode Interface (REMI) that guides re
      growing axons through an electrode array deployed in the lumen of a nerve guide.
      While acute studies have shown the use of the REMI in the rat sciatic nerve, the
      quality of chronic signal recording has not been reported. Here we show that
      implantation of this interface in the sciatic nerve is stable with high quality
      recordings up to 120 days and failures mainly attributable to abiotic factors
      related to pedestal detachment and wire breakage. We further tested the
      interfacing of REMI with fascicles of the sciatic nerve that primarily innervate
      muscles (tibial) and skin (sural). When implanted into the tibial nerve, bursting
      activity was observed synchronous to stepping. However, implantation of REMI into
      the sural nerve failed due to its small size. While fascicles smaller than 300
      MUm are a challenge for regenerative interfacing, we show that a modified REMI
      can be used in an insertion mode to record sensory signals from skin. In summary,
      the REMI represents an effective tool for recording firing patterns of specific
      axon types during voluntary movement, which may be used to improve the motor
      control and sensory feedback in closed loop control systems for robotic
      prosthesis. 

PMID- 25570369
TI  - Using multiple high-count electrode arrays in human median and ulnar nerves to
      restore sensorimotor function after previous transradial amputation of the hand.
AB  - Peripheral nerve interfaces that can record from and stimulate large numbers of
      different nerve fibers selectively and independently may help restore intuitive
      and effective motor and sensory function after hand amputation. To this end, and
      extending previous work in two subjects, two 100-electrode Utah Slanted Electrode
      Arrays (USEAs) were implanted for four weeks in the residual ulnar and median
      nerves of a 50-year-old male whose left, dominant hand had been amputated 21
      years previously. Subsequent experiments involved 1) recording from USEAs for
      real-time control of a virtual prosthetic hand; 2) stimulation to evoke
      somatosensory percepts; and 3) closed-loop sensorimotor control. Overall, partial
      motor control and sensation were achieved using USEAs. 1) Isolated action
      potentials recorded from nerve motor fibers, although sparse at these distal
      implant sites, were activated during fictive movements of the phantom hand.
      Unlike in our previous two subjects, electromyographic (EMG) activity contributed
      to most online recordings and decodes, but was reduced in offline analyses using
      common average referencing. Online and offline Kalman-filter decodes of
      thresholded neural or EMG spikes independently controlled different digits of the
      virtual hand with one or two degrees of freedom. 2) Microstimulation through
      individual electrodes of the two USEAs evoked up to 106 different percepts,
      covering much of the phantom hand. The subject discriminated among five perceived
      stimulus locations, and between two somatosensory submodalities at a single
      location. 3) USEA-evoked percepts, mimicking contact with either a near or distal
      virtual target, were used to terminate movements of the virtual hand controlled
      with USEA recordings comprised wholly or mostly of EMG. These results further
      indicate that USEAs can help restore sensory and motor function after hand loss. 

PMID- 25570370
TI  - A novel Microchannel Electrode Array: towards bioelectronic medical interfacing
      of small peripheral nerves.
AB  - Bioelectronic medicine is an emerging field that relies on electrical signals to
      modulate complex neuronal circuits, particularly in the peripheral nervous
      system, as an alternative to drug-enabled therapeutics. Small autonomic nerves
      are one of the targets in this field, however, interfacing peripheral nerves
      smaller than 300 MUm remains a challenge. Here we report the development of a
      Microchannel Electrode Array (DCEA) capable of interfacing nerve fascicles as
      small as 50-300MUm. The current MUCEA records and stimulates from 28 channels and
      is designed for easy implantation and removal, bearing promise to enable neural
      interfacing in BM. 

PMID- 25570371
TI  - A chronic window imaging device for the investigation of in vivo peripheral
      nerves.
AB  - Chronic imaging of the peripheral nervous system with contemporary techniques
      requires repetitive surgical procedures to reopen an area of interest in order to
      see underlying biological processes over time. The recurrence of surgical
      openings on an animal increases trauma, stress, and risk of infection. Such
      effects can greatly lessen the physiological relevance of any data recorded in
      this manner. In order to bypass repetitive surgery, a Peripheral Nerve Window
      (PNW) device has been created for chronic in vivo imaging purposes. Intravital
      imaging window devices have been used previously to image parts of the rodent
      model such as the brain, spinal cord, and mammary tissue, but currently have not
      been used in the peripheral nervous system because of lack of bone anchoring and
      access to deep nerve tissue. We demonstrate a novel surgical technique in a rat
      which transposes the sciatic nerve above the surrounding muscle tissue allowing
      the PNW access to an 8mm section of the nerve. Subsequent days of observation
      revealed increased vasculature development primarily around the nerve, showing
      that this preparation can be used to image nerve tissue and surrounding
      vasculature for up to one week post-implantation. 

PMID- 25570372
TI  - Electrically stimulated signals from a long-term Regenerative Peripheral Nerve
      Interface.
AB  - Despite modern technological advances, the most widely available prostheses
      provide little functional recovery beyond basic grasping. Although sophisticated
      upper extremity prostheses are available, optimal prosthetic interfaces which
      give patients high-fidelity control of these artificial limbs are limited. We
      have developed a novel Regenerative Peripheral Nerve Interface (RPNI), which
      consists of a unit of free muscle that has been neurotized by a transected
      peripheral nerve. In conjunction with a biocompatible electrode on the muscle
      surface, the RPNI facilitates signal transduction from a residual peripheral
      nerve to a neuroprosthetic limb. The purpose of this study was to explore signal
      quality and reliability in an RPNI following an extended period of implantation.
      Following a 14-month maturation period, electromyographic signal generation was
      evaluated via electrical stimulation of the innervating nerve. The long-term RPNI
      was viable and healthy, as demonstrated by evoked compound muscle action
      potentials as well as histological tissue analysis. Signals exceeding 4 mV were
      successfully acquired and amplitudes were consistent across multiple repetitions
      of applied stimuli. There were no evident signs of muscle denervation,
      significant scar tissue, or muscle necrosis. This study provides further evidence
      that after a maturation period exceeding 1 year, reliable and consistent signals
      can still be acquired from an RPNI. 

PMID- 25570373
TI  - NGF-loaded PLGA microparticles for advanced multifunctional regenerative
      electrodes.
AB  - Nerve guide conduits are currently the elective device for peripheral nerve
      reconstruction applications, as nerve autograft often is hampered by procedure
      invasiveness and limited nerve availability. Many technological improvements have
      been approached to enhance nerve regeneration driven by these devices, whose main
      drawbacks are often disordered sprouting and ineffective axon guidance. Among the
      adopted solutions to overcome these problems, embedding of extracellular matrix
      (ECM) proteins and neurotrophic factors (NF) in nerve conduits has been a
      promising one. Using free NFs, however suffers from different drawbacks mainly
      due to diffusion, degradation and local concentration boosting. As part of a
      wider EU-funded program for next gen regenerative electrodes, we developed NGF
      loaded PLGA microparticles to use them immersed in a gel biomatrix that is being
      embedded in nerve conduits before implant, and allow for timed-controlled
      delivery instead of an initial concentration boost. Here we report the
      technological steps for the synthesis and initial testing with mouse dorsal root
      ganglia (DRG) explants, towards their full integration with a complex three
      dimensional biomatrix into next-gen regeneration electrodes. 

PMID- 25570374
TI  - A review of past and future near-infrared spectroscopy brain computer interface
      research at the PRISM lab.
AB  - Single-trial classification of near-infrared spectroscopy (NIRS) signals for
      brain-computer interface (BCI) applications has recently gained much attention.
      This paper reviews research in this area conducted at the PRISM lab (University
      of Toronto) to date, as well as directions for future work. Thus far, research
      has included classification of hemodynamic changes induced by the performance of
      various mental tasks in both offline and online settings, as well as offline
      classification of cortical changes evoked by different affective states. The
      majority of NIRS-BCI work has only involved able-bodied individuals. However,
      preliminary work involving individuals from target BCI-user populations is also
      underway. In addition to further testing with users with severe disabilities,
      ongoing and future research will focus on enhancing classification accuracies,
      communication speed and user experience. 

PMID- 25570375
TI  - Evaluating a four-class motor-imagery-based optical brain-computer interface.
AB  - This work investigates the potential of a four-class motor-imagery-based brain
      computer interface (BCI) using functional near-infrared spectroscopy (fNIRS).
      Four motor imagery tasks (right hand, left hand, right foot, and left foot
      tapping) were executed while motor cortex activity was recorded via fNIRS.
      Preliminary results from three participants suggest that this could be a viable
      BCI interface, with two subjects achieving 50% accuracy. fNIRS is a noninvasive,
      safe, portable, and affordable optical brain imaging technique used to monitor
      cortical hemodynamic changes. Because of its portability and ease of use, fNIRS
      is amenable to deployment in more natural settings. Electroencephalography (EEG)
      and functional magnetic resonance imaging (fMRI) BCIs have already been used with
      up to four motor-imagery-based commands. While fNIRS-based BCIs are relatively
      new, success with EEG and fMRI systems, as well as signal characteristics similar
      to fMRI and complementary to EEG, suggest that fNIRS could serve to build or
      augment future BCIs. 

PMID- 25570376
TI  - Single trial classification of fNIRS-based brain-computer interface mental
      arithmetic data: a comparison between different classifiers.
AB  - Functional near infrared spectroscopy (fNIRS) is an emerging technique for the in
      vivo assessment of functional activity of the cerebral cortex as well as in the
      field of brain-computer-interface (BCI) research. A common challenge for the
      utilization of fNIRS for BCIs is a stable and reliable single trial
      classification of the recorded spatio-temporal hemodynamic patterns. Many
      different classification methods are available, but up to now, not more than two
      different classifiers were evaluated and compared on one data set. In this work,
      we overcome this issue by comparing five different classification methods on
      mental arithmetic fNIRS data: linear discriminant analysis (LDA), quadratic
      discriminant analysis (QDA), support vector machines (SVM), analytic shrinkage
      regularized LDA (sLDA), and analytic shrinkage regularized QDA (sQDA). Depending
      on the used method and feature type (oxy-Hb or deoxy-Hb), achieved classification
      results vary between 56.1 % (deoxy-Hb/QDA) and 86.6% (oxy-Hb/SVM). We
      demonstrated that regularized classifiers perform significantly better than non
      regularized ones. Considering simplicity and computational effort, we recommend
      the use of sLDA for fNIRS-based BCIs. 

PMID- 25570377
TI  - Single-trial classification of NIRS data from prefrontal cortex during working
      memory tasks.
AB  - This study presents single-trial classification performance on high density Near
      Infrared Spectroscopy (NIRS) data collected from the prefrontal cortex of 11
      healthy subjects while performing working memory tasks and idle condition. The
      NIRS data collected comprised a total of 40 trials of n-back tasks for 2
      difficulty levels: n=1 for easy and n=3 for hard. The single-trial classification
      was performed on features extracted using common average reference spatial
      filtering and single-trial baseline reference. The single-trial classification
      was performed using 5*5-fold cross-validations on the NIRS data collected by
      using mutual information-based feature selection and the support vector machine
      classifier. The results yielded average accuracies of 72.7%, 68.0% and 84.0% in
      classifying hard versus easy tasks, easy versus idle tasks and hard versus idle
      tasks respectively. Hence the results demonstrated a potential feasibility of
      using high density NIRS-based BCI for assessing working memory load. 

PMID- 25570378
TI  - Combining feature extraction and classification for fNIRS BCIs by regularized
      least squares optimization.
AB  - In this paper, we show that multiple operations of the typical pattern
      recognition chain of an fNIRS-based BCI, including feature extraction and
      classification, can be unified by solving a convex optimization problem. We
      formulate a regularized least squares problem that learns a single affine
      transformation of raw HbO(2) and HbR signals. We show that this transformation
      can achieve competitive results in an fNIRS BCI classification task, as it
      significantly improves recognition of different levels of workload over
      previously published results on a publicly available n-back data set.
      Furthermore, we visualize the learned models and analyze their spatio-temporal
      characteristics.

PMID- 25570379
TI  - A smart homecage system with 3D tracking for long-term behavioral experiments.
AB  - A wirelessly-powered homecage system, called the EnerCage-HC, that is equipped
      with multi-coil wireless power transfer, closed-loop power control, optical
      behavioral tracking, and a graphic user interface (GUI) is presented for long
      term electrophysiology experiments. The EnerCage-HC system can wirelessly power a
      mobile unit attached to a small animal subject and also track its behavior in
      real-time as it is housed inside a standard homecage. The EnerCage-HC system is
      equipped with one central and four overlapping slanted wire-wound coils (WWCs)
      with optimal geometries to form 3-and 4-coil power transmission links while
      operating at 13.56 MHz. Utilizing multi-coil links increases the power transfer
      efficiency (PTE) compared to conventional 2-coil links and also reduces the
      number of power amplifiers (PAs) to only one, which significantly reduces the
      system complexity, cost, and dissipated heat. A Microsoft Kinect installed 90 cm
      above the homecage localizes the animal position and orientation with 1.6 cm
      accuracy. An in vivo experiment was conducted on a freely behaving rat by
      continuously delivering 24 mW to the mobile unit for > 7 hours inside a standard
      homecage. 

PMID- 25570380
TI  - Electrochemical biochip for applications to wireless and batteryless monitoring
      of free-moving mice.
AB  - A multi-sensing platform for applications in wireless and batteryless monitoring
      of free-moving small animals is presented in this paper. The proposed platform
      hosts six sensors: four biosensors for sensing of both disease biomarkers and
      therapeutic compounds, and two further sensors (T and pH) for biosensor
      calibration. Electrodeposition of Multi-Walled Carbon Nanotubes (MWCNTs) and the
      subsequent function-alization with proper enzymes is used to assure sensitivity
      and specificity in electrochemical biosensing. The realized sensors are
      demonstrated to be capable of measuring several parameters: lactate with a
      sensitivity of 77+/-26 MUA/mM. cm(2) and a limit of detection (LOD) of 4+/-1 MUM;
      glucose with a sensitivity of 63+/-15 MUA/mM. cm(2) and a LOD of 8+/-2 MUM;
      Etoposide (a well known anti-cancer agent) with a sensitivity of 0.15+/-0.04
      mA/mM. cm(2) and a LOD of 4+/-1 MUM; Open Circuit Potential (OCP) measurements
      are used on a Pt/IrOx junction to sense pH with a sensitivity of around -75+/
      5mV/pH; while a Pt resistive thermal device is used to measure physiological
      temperature-range with an average sensitivity of 0.108+/-0.001 kOmega/ degrees C.

PMID- 25570381
TI  - Towards a wireless optical stimulation system for long term in-vivo experiments.
AB  - This paper presents our recent progresses towards the development of a wirelessly
      powered head mountable optical stimulator for enabling long-term optogenetic
      experiments with small freely moving transgenic models. The proposed system
      includes a wireless power transmission chamber with uniform power distribution in
      3D and a wireless head mountable optical stimulator prototype with power
      recovery. The wireless power link, which includes the inductive chamber and power
      recovery circuits, is robust against subject movements in all directions, and
      against angular misalignment. Such link provides uniform power distribution
      without the need for a closed-loop control system, and can localize the
      transmitted power towards the receiver, without using additional detection and
      control circuitry compared to other systems. Additionally, the chamber is
      equipped with a camera for capturing the animal motion and behavior after
      applying optical stimulation patterns. A low-power microcontroller unit is
      embedded with the stimulator prototype to generate arbitrary light stimulation
      patterns. Measurement results show that the inductive chamber can continuously
      deliver 70 mW to the stimulator prototype with a power efficiency of 59%. 

PMID- 25570382
TI  - Remote powering platform for implantable sensor systems at 2.45 GHz.
AB  - Far-field remotely powered sensor systems enable long distance operation for low
      power sensor systems. In this work, we demonstrate a remote powering platform
      with a miniaturized antenna and remote powering base station operating at 2.45
      GHz. The rectenna, which is the energy receiving and conversion element of the
      sensor system, is designed and measured. The measurements for the tag are
      performed within 15 cm distance from the remote powering base station. The
      realized gain of the tag antenna is measured as -3.3 dB, which is 0.5 dB close to
      the simulations, where simulated realized gain is -2.8 dB. 

PMID- 25570383
TI  - Ultra-high-density in-vivo neural probes.
AB  - The past decade has witnessed an explosive growth in our ability to observe and
      measure brain activity. Among different functional brain imaging techniques, the
      electrical measurement of neural activity using neural probes provides highest
      temporal resolution. Yet, the electrode density and the observability of
      currently available neural probe technologies fall short of the density of
      neurons in the brain by several orders of magnitude. This paper presents
      opportunities for neural probes to utilize advances in CMOS technology for
      increasing electrode density and observability of neural activity, while
      minimizing the tissue damage. The authors present opportunities for neural probes
      to adapt advanced CMOS technologies and discuss challenges in terms of
      maintaining the signal integrity and implementing data communication. 

PMID- 25570384
TI  - Real-time processing of fast-scan cyclic voltammetry (FSCV) data using a field
      programmable gate array (FPGA).
AB  - This paper reports the hardware implementation of a digital signal processing
      (DSP) unit for real-time processing of data obtained by fast-scan cyclic
      voltammetry (FSCV) at a carbon-fiber microelectrode (CFM), an electrochemical
      transduction technique for high-resolution monitoring of brain neurochemistry.
      Implemented on a field-programmable gate array (FPGA), the DSP unit comprises a
      decimation filter and an embedded processor to process the oversampled FSCV data
      and obtain in real time a temporal profile of concentration variation along with
      a chemical signature to identify the target neurotransmitter. Interfaced with an
      integrated, FSCV-sensing front-end, the DSP unit can successfully process FSCV
      data obtained by bolus injection of dopamine in a flow cell as well as
      electrically evoked, transient dopamine release in the dorsal striatum of an
      anesthetized rat. 

PMID- 25570385
TI  - Haptic fMRI: accurately estimating neural responses in motor, pre-motor, and
      somatosensory cortex during complex motor tasks.
AB  - Haptics combined with functional magnetic resonance imaging (Haptic fMRI) can non
      invasively study how the human brain coordinates movement during complex
      manipulation tasks, yet avoiding associated fMRI artifacts remains a challenge.
      Here, we demonstrate confound-free neural activation measurements using Haptic
      fMRI for an unconstrained three degree-of-freedom motor task that involves
      planning, reaching, and visually guided trajectory tracking. Our haptic interface
      tracked subjects' hand motions, velocities, and accelerations (sample-rate,
      350Hz), and provided continuous realtime visual feedback. During fMRI
      acquisition, we achieved uniform response latencies (reaching, 0.7-1.1s;
      tracking, 0.4-0.65s); minimized hand jitter (<;8mm); and ensured reliable motion
      trajectories (tracking, <;7mm root-mean-square error). In addition, our protocol
      decorrelated head motion from both hand speed (r=-0.03) and acceleration (r=
      0.025), which reliably produced low head motion levels (<;0.4mm/s between scan
      volumes) and a low fMRI temporal noise-to-signal ratio (<;1%) across thirty-five
      scan runs. Our results address the primary outstanding Haptic fMRI confounds:
      motion induced low spatial-frequency magnetic field changes, which correlate
      neural activation across cortex; unreliable motions and response latencies, which
      reduce statistical power; and task-correlated head motion, which causes spurious
      fMRI activation. Haptic fMRI can thus reliably elicit and localize heterogeneous
      neural activation for different tasks in motor (movement), pre-motor (planning),
      and somatosensory (limb displacement) cortex, demonstrating that it is feasible
      to use the technique to study how the brain achieves three dimensional motor
      control. 

PMID- 25570386
TI  - Haptic fMRI: using classification to quantify task-correlated noise during goal
      directed reaching motions.
AB  - Neuroimaging artifacts in haptic functional magnetic resonance imaging (Haptic
      fMRI) experiments have the potential to induce spurious fMRI activation where
      there is none, or to make neural activation measurements appear correlated across
      brain regions when they are actually not. Here, we demonstrate that performing
      three-dimensional goal-directed reaching motions while operating Haptic fMRI
      Interface (HFI) does not create confounding motion artifacts. To test for
      artifacts, we simultaneously scanned a subject's brain with a customized soft
      phantom placed a few centimeters away from the subject's left motor cortex. The
      phantom captured task-related motion and haptic noise, but did not contain
      associated neural activation measurements. We quantified the task-related
      information present in fMRI measurements taken from the brain and the phantom by
      using a linear max-margin classifier to predict whether raw time series data
      could differentiate between motion planning or reaching. fMRI measurements in the
      phantom were uninformative (2sigma, 45-73%; chance=50%), while those in primary
      motor, visual, and somatosensory cortex accurately classified task-conditions
      (2sigma, 90-96%). We also localized artifacts due to the haptic interface alone
      by scanning a stand-alone fBIRN phantom, while an operator performed haptic tasks
      outside the scanner's bore with the interface at the same location. The stand
      alone phantom had lower temporal noise and had similar mean classification but a
      tighter distribution (bootstrap Gaussian fit) than the brain phantom. Our results
      suggest that any fMRI measurement artifacts for Haptic fMRI reaching experiments
      are dominated by actual neural responses. 

PMID- 25570388
TI  - Multiple-Input/Single-Output identification of the dynamic relation between EMG
      and torque at the human ankle during isometric contractions.
AB  - Generation of torque around a joint usually involves the activation of several
      agonist muscles and may also involve the co-activation of antagonist muscles.
      Therefore, a valid model for the dynamic relation between surface EMG (an
      indirect measured of the muscle's neural input) and the torque should take the
      form of a Multiple-Input/Single-Output (MISO) system to account for the
      contributions of the different muscles. This paper presents a new method to
      accurately estimate the dynamic EMG/Torque relation when multiple muscles are
      active simultaneously. Using our method we found that flexor and extensor muscles
      at the ankle have different dynamic properties. 

PMID- 25570387
TI  - Mapping stiffness perception in the brain with an fMRI-compatible particle
      jamming haptic interface.
AB  - We demonstrate reliable neural responses to changes in haptic stiffness
      perception using a functional magnetic resonance imaging (fMRI) compatible
      particle-jamming haptic interface. Our haptic interface consists of a silicone
      tactile surface whose stiffness we can control by modulating air-pressure in a
      sub-surface pouch of coarsely ground particles. The particles jam together as the
      pressure decreases, which stiffens the surface. During fMRI acquisition, subjects
      performed a constant probing task, which involved continuous contact between the
      index fingertip and the interface and rhythmic increases and decreases in
      fingertip force (1.6 Hz) to probe stiffness. Without notifying subjects, we
      randomly switched the interface's stiffness (switch time, 300-500 ms) from soft
      (200 N/m) to hard (1400 N/m). Our experiment design's constant motor activity and
      cutaneous tactile sensation helped disassociate neural activation for both from
      stiffness perception, which helped localized it to a narrow region in
      somatosensory cortex near the supra-marginal gyrus. Testing different models of
      neural activation, we found that assuming indepedent stiffness-change responses
      at both soft-hard and hard-soft transitions provides the best explanation for
      observed fMRI measurements (three subjects; nine four-minute scan runs each).
      Furthermore, we found that neural activation related to stiffness-change and
      absolute stiffness can be localized to adjacent but disparate anatomical
      locations. We also show that classical finger-tapping experiments activate a
      swath of cortex and are not suitable for localizing stiffness perception. Our
      results demonstrate that decorrelating motor and sensory neural activation is
      essential for characterizing somatosensory cortex, and establish particle-jamming
      haptics as an attractive low-cost method for fMRI experiments. 

PMID- 25570389
TI  - Design of a knee joint mechanism that adapts to individual physiology.
AB  - This paper describes the design of a new knee joint mechanism, called the
      Adaptive Coupling Joint (ACJ). The new mechanism has an adaptive trajectory of
      the center of rotations (COR) that automatically matches those of the attached
      biological joint. The detailed design is presented as well as characterization
      results of the ACJ. Conventional exoskeleton and assistive devices usually
      consider limb joints as a one to three degrees of freedom (DOFs) joint
      synthesized by multiple one-DOF hinge joints in a single plane. However, the
      biological joints are complex and usually rotate with respect to a changing COR.
      As a result, the mismatch between limb joint motion and mechanical interface
      motion can lead to forces that cause undesired ligament and muscle length changes
      and internal mechanical changes. These undesired changes contribute to
      discomfort, as well as to the slippage and sluggish interaction between humans
      and devices. It is shown that the ACJ can transmit planetary torques from either
      active or passive devices to the limbs without altering the normal biological
      joint motion. 

PMID- 25570390
TI  - A new design for the BirthSIM simulator to improve realism.
AB  - This paper presents a new design of the BirthSIM simulator. Its goal is to help
      obstetricians and midwives to train and improve their skills during childbirth
      delivery. The new version of the BirthSIM is more actuated than the previous
      version in order to be more biofidelic and cover various scenarios. The direct
      and inverse geometric models of the haptic interface are presented. The working
      space reached by the fetal head is computed and validates the proposed design
      which allows to reproduce all fetal head trajectories inside the pelvis. The
      novelty is illustrated by an example which presents a simulated trajectory
      stemmed from a sacrum shape measure. The inverse geometric model allows to
      compute the actuators displacements and thus to validate the chosen components. 

PMID- 25570391
TI  - Protein-protein binding detection with nanoparticle photonic crystal enhanced
      microscopy (NP-PCEM).
AB  - We demonstrate a novel microscopy-based biosensing approach that utilizes a
      photonic crystal (PC) surface to detect protein-protein binding with the
      functionalized nanoparticles as tags. This imaging approach utilizes the
      measurement of localized shifts in the resonant wavelength and resonant
      reflection magnitude from the PC biosensor in the presence of individual
      nanoparticles. Moreover, it substantially increases the sensitivity of the
      imaging approach through tunable localized surface plasmon resonant frequency of
      the nanoparticle matching with the resonance of the PC biosensor. Experimental
      demonstrations of photonic crystal enhanced microscopy (PCEM) imaging with single
      nanoparticle resolution are supported by Finite-Difference Time-Domain (FDTD)
      computer simulations. The ability to detect the surface adsorption of individual
      nanoparticles as tags offers a route to single molecule biosensing with photonic
      crystal biosensor in the future. 

PMID- 25570392
TI  - Detection of protein-small molecule binding using a self-referencing external
      cavity laser biosensor.
AB  - High throughput screening of protein-small molecule binding interactions using
      label-free optical biosensors is challenging, as the detected signals are often
      similar in magnitude to experimental noise. Here, we describe a novel self
      referencing external cavity laser (ECL) biosensor approach that achieves high
      resolution and high sensitivity, while eliminating thermal noise with sub
      picometer wavelength accuracy. Using the self-referencing ECL biosensor, we
      demonstrate detection of binding between small molecules and a variety of
      immobilized protein targets with binding affinities or inhibition constants in
      the sub-nanomolar to low micromolar range. The demonstrated ability to perform
      detection in the presence of several interfering compounds opens the potential
      for increasing the throughput of the approach. As an example application, we
      performed a "needle-in-the-haystack" screen for inhibitors against carbonic
      anhydrase isozyme II (CA II), in which known inhibitors are clearly
      differentiated from inactive molecules within a compound library. 

PMID- 25570393
TI  - Optical analysis of lithium carbonate: towards the development of a portable
      lithium blood level analyzer for bipolar disorder patients.
AB  - Lithium medication is the gold standard of treatment in Bipolar Disorder
      patients, preventing and reducing mood swings and suicidality. However, despite
      its effectiveness, it is a potentially hazardous drug requiring regular
      monitoring of blood levels to ensure toxic levels are not reached. This paper
      describes the first steps towards developing a new portable device that can be
      used by Bipolar Disorder patients to facilitate the analysis of lithium blood
      levels at home. Solutions of lithium carbonate have been optically fingerprinted
      using a high-end spectrophotometer. Preliminary measurements indicate that while
      the visible to near infrared region of the absorption spectra fall heavily within
      the water band, measurements in the Ultraviolet region show a strong distinction
      between different lithium concentrations. The optical spectra of Lithium in the
      220 nm to 230 nm region demonstrated the ability to differentiate between
      concentrations representing those found in patients. 

PMID- 25570394
TI  - Dynamic modeling of the hydrogel molecular filter in a metamaterial biosensing
      system for glucose concentration estimation.
AB  - We present a novel concept for ophthalmic glucose sensing using a biosensing
      system that consists of plasmonic dipole metamaterial covered by a layer of
      functionalized hydrogel. The metamaterial together with the hydrogel can be
      integrated into a contact lens. This optical sensor changes its properties such
      as reflectivity upon the ambient glucose concentration, which allows in situ
      measurements in the eye. The functionalization of the sensor with hydrogel allows
      for a glucose-specific detection, providing both selectivity and sensitivity. As
      a result of the presented work we derive a dynamic model of the hydrogel that can
      be used for further simulation studies. 

PMID- 25570395
TI  - Fabrication of flexible microlens array through vapor-induced room temperature
      dewetting on plasma treated Parylene-C.
AB  - Microlens arrays have been widely used as an essential component in many optical
      systems. The conventional fabrication techniques, such as ink-jet printing,
      photoresist thermal reflow, grayscale photolithography, and LIGA process have
      some drawbacks in aspects of process complexity and high fabrication cost. This
      paper presents a low-temperature, rapid and cost-effective method to successfully
      generate SU-8 microlens arrays on biocompatible Parylene-C surfaces. Vapor
      induced SU-8 dewetting has been achieved on chemically modified Parylene-C
      surfaces that were selectively pre-treated with O(2) or SF(6) plasma. By this
      technique, the SU-8 droplets are self-organized onto desired positions to form a
      microlens array. This method is also suitable for production of microlens array
      on curved surfaces. The progress of dewetting has been studied by both experiment
      and simulation.

PMID- 25570396
TI  - Implantable pulse oximetry on subcutaneous tissue.
AB  - Blood oxygen saturation is one of the most prominent measurement parameters in
      daily clinical routine. However up to now, it is not possible to continuously
      monitor this parameter reliably in mobile patients. High-risk patients suffering
      from cardiovascular diseases could benefit from long-term monitoring of blood
      oxygen saturation. In this paper, we present a minimally invasive, implantable
      patient monitor which is capable of monitoring vital signs. The capability of
      this multimodal sensor to subcutaneously determine blood pressure, pulse and ECG
      has been demonstrated earlier. This paper focuses on monitoring of blood oxygen
      saturation. Even though the signal amplitudes are much weaker than for standard
      extracorporeal measurements, photoplethysmographic signals were recorded with
      high quality in vivo directly on subcutaneous muscle tissue. For the first time,
      it has been shown that blood oxygen saturation can be measured with an
      implantable, but extravascular sensor. The sensor was implanted for two weeks in
      a sheep and did not cause any complications. This opens new perspectives for home
      monitoring of patients with cardiovascular diseases. 

PMID- 25570397
TI  - Modular organization of reaching and grasping movements investigated using EEG
      microstates.
AB  - How movements are generated and controlled by the central nervous system (CNS) is
      still not well understood. In this work, we tested the hypothesis of a modular
      organization of the brain activity during the execution of voluntary movements.
      In particular, we extracted meta-stable topographies as a measure for global
      brain state, so-called microstates, from electroencephalography (EEG) data during
      pure planar reaching movements as well as reaching and grasping of different
      objects, and we compared them with those extracted during resting-state. The
      results showed the emergence of specific EEG microstates related to movement
      execution. Our results provide evidence about the benefits of EEG microstate
      analysis for motor control studies and their importance to better understand
      brain reorganization in neurological pathologies. 

PMID- 25570398
TI  - Cortical activation of passive hand movement using Haptic Knob: a preliminary
      multi-channel fNIRS study.
AB  - Several functional neuroimaging studies had been performed to explore the
      sensorimotor function for motor imagery and passive movement, but there is scanty
      work that investigated the cortical activation pattern for passive movement using
      functional Near-Infrared Spectroscopy (fNIRS). This study investigated the
      cortical activation pattern from fNIRS data of 8 healthy subjects performing
      motor imagery and passive movement tasks using a Haptic Knob robot. Group
      averaged contrasts were defined as motor imagery versus idle and passive movement
      versus idle. The cortical activations for motor imagery appeared on the
      contralateral sensorimotor area, whereas the cortical activations for passive
      movement appeared on both contralateral and ipsilateral sensorimotor area. This
      result suggests that the performance of passive movement has a wider cortical
      activation compared to the performance of motor imagery. 

PMID- 25570399
TI  - Development of an MR-compatible configurable brush stimulation device.
AB  - In order to evaluate sensory disturbance, a subjective method is performed, so
      that the evaluation result is influenced by subjective factors. fMRI is used for
      observing brain activity objectively. Therefore the brain response to a
      stimulation measured by fMRI could become a useful identification tool for the
      objective evaluation of the sensory disturbance. The purpose of this study is to
      develop an MR-compatible sensory stimulation device capable of providing brush
      stimulation to several positions with separate modules, and to confirm the
      feasibility of the device by a basic operation experiment and an fMRI experiment.
      The developed device consists of both an MR-compatible stimulator placed inside
      the MRI room, a tube-rod mechanism and a driver placed outside the MRI room. The
      tube-rod mechanism is adopted for power transmission from the driver to the
      stimulator. Also, in order to provide the stimulation to several positions in the
      limited space, the device consists of the stimulation module and the positioning
      module that moves the stimulation module. For the basic operation experiment, we
      measure a variation of the automated and manual brush stimulation period. For the
      fMRI experiment, the brush stimulation is provided to the middle fingertip and
      the palm of a subject in a trial using the developed device. As a result, the
      standard deviations of the automated brush stimulation period is less than 7.0
      ms. This result was smaller than that of the manual stimulation period. Also, the
      brush stimulation to the fingertip and the palm activated the somatosensory areas
      respectively. In conclusion, we confirmed the feasibility of the developed device
      through the experiments. 

PMID- 25570400
TI  - Moving Average Convergence Divergence filter preprocessing for real-time event
      related peak activity onset detection : application to fNIRS signals.
AB  - Real-time solutions for noise reduction and signal processing represent a central
      challenge for the development of Brain Computer Interfaces (BCI). In this paper,
      we introduce the Moving Average Convergence Divergence (MACD) filter, a tunable
      digital passband filter for online noise reduction and onset detection without
      preliminary learning phase, used in economic markets analysis. MACD performance
      was tested and benchmarked with other filters using data collected with
      functional Near Infrared Spectoscopy (fNIRS) during a digit sequence memorization
      task. This filter has a good performance on filtering and real-time peak activity
      onset detection, compared to other techniques. Therefore, MACD could be
      implemented for efficient BCI design using fNIRS. 

PMID- 25570401
TI  - User-driven control increases cortical activity during treadmill walking: an EEG
      study.
AB  - Treadmills provide a safe and efficient method for gait rehabilitation but
      treadmill based training paradigms have not been shown to create superior results
      when compared with traditional physical therapy methods such as overground
      training. One explanation for this may be that walking at a constant, fixed speed
      requires little mental engagement from the user, which has been postulated as a
      key factor in the success of motor learning. To increase mental engagement, we
      developed a user-driven treadmill control scheme. In this paper we use
      electroencephalography (EEG) to compare cortical activity during user-driven
      (active) walking with activity on a normal (passive) treadmill in nine healthy
      subjects. We used independent component analysis (ICA) to isolate brain activity
      from artifactual components. We fit equivalent dipole sources to each brain
      component and clustered these across subjects. Our analysis revealed that
      relative to the passive treadmill, active walking resulted in statistically
      significant decreases in spectral power, i.e. desynchronization, in the anterior
      cingulate, sensorimotor cortices, and posterior parietal lobe of the cortex.
      These results indicate that user-driven treadmills more fully engage the motor
      cortex and therefore could facilitate better training outcomes than a traditional
      treadmill. 

PMID- 25570402
TI  - Decoding of intentional actions from scalp electroencephalography (EEG) in freely
      behaving infants.
AB  - The mirror neuron system (MNS) in humans is thought to enable an individual's
      understanding of the meaning of actions performed by others and the potential
      imitation and learning of those actions. In humans, electroencephalographic (EEG)
      changes in sensorimotor a-band at central electrodes, which desynchronizes both
      during execution and observation of goal-directed actions (i.e., MU suppression),
      have been considered an analog to MNS function. However, methodological and
      developmental issues, as well as the nature of generalized MU suppression to
      imagined, observed, and performed actions, have yet to provide a mechanistic
      relationship between EEG MU-rhythm and MNS function, and the extent to which EEG
      can be used to infer intent during MNS tasks remains unknown. In this study we
      present a novel methodology using active EEG and inertial sensors to record brain
      activity and behavioral actions from freely-behaving infants during exploration,
      imitation, attentive rest, pointing, reaching and grasping, and interaction with
      an actor. We used 5-band (1-4Hz) EEG as input to a dimensionality reduction
      algorithm (locality-preserving Fisher's discriminant analysis, LFDA) followed by
      a neural classifier (Gaussian mixture models, GMMs) to decode the each MNS task
      performed by freely-behaving 6-24 month old infants during interaction with an
      adult actor. Here, we present results from a 20-month male infant to illustrate
      our approach and show the feasibility of EEG-based classification of freely
      occurring MNS behaviors displayed by an infant. These results, which provide an
      alternative to the MU-rhythm theory of MNS function, indicate the informative
      nature of EEG in relation to intentionality (goal) for MNS tasks which may
      support action-understanding and thus bear implications for advancing the
      understanding of MNS function. 

PMID- 25570403
TI  - A non-contact vision-based system for respiratory rate estimation.
AB  - A non-contact vision-based system is presented for continuous respiratory rate
      monitoring. The system identifies feature points in a video feed and tracks them
      over time. Two methods are presented for comparison - a method which uses
      principal component analysis (PCA) and a simple averaging approach. These methods
      condense the feature point trajectories into a compact set of representative
      signals. The signal which most closely resembles an expected respiratory trace is
      selected based on spectral analysis. System performance is assessed by comparing
      the estimated respiratory rate to the rate determined via inductance
      plethysmogram. The system was evaluated on 5 participants in 4 simulated sleep
      scenarios. Accuracies of within 1 breath/minute were achieved for more than 97%
      of the recorded time in all scenarios. The proposed system is accurate, cost
      effective, and simple, making it a suitable candidate for at-home installation. 

PMID- 25570404
TI  - Design, development and experimental validation of a non-invasive device for
      recording respiratory events during bottle feeding.
AB  - In newborns, a poor coordination between sucking, swallowing and breathing may
      undermine the effectiveness of oral feeding and signal immaturity of Central
      Nervous System. The aim of this work is to develop and validate a non-invasive
      device for recording respiratory events of newborns during bottle feeding. The
      proposed device working principle is based on the convective heat exchanged
      between two hot bodies and the infants' breathing. The sensing elements are
      inserted into a duct and the gas exchanged by infants is conveyed into this duct
      thanks to an ad hoc designed system to be mounted on a commercial feeding bottle.
      Two sets of experiments have been carried out in order to investigate the
      discrimination threshold of the device and characterize the sensor response at
      oscillating flows. The effect of distance and tilt between nostrils and device,
      and the breathing frequency, have been investigated simulating nostrils and
      neonatal respiratory pattern. The device has a discrimination threshold lower
      than 0.5 L/min at both 10 degrees  and 20 degrees  of tilt. Distance for these
      two settings does not affect the threshold in the investigated range (10-20 mm).
      Moreover, the device is able to detect breathing events, and to discriminate the
      onset of expiratory phase, during a neonatal respiratory task delivered by a lung
      simulator. The results foster the successful application of this device to the
      assessment of the temporal breathing pattern of newborns during bottle feeding
      with a non-invasive approach. 

PMID- 25570406
TI  - A transistors-based, bidirectional flowmeter for neonatal ventilation: design and
      experimental characterization.
AB  - A bidirectional, low cost flowmeter for neonatal artificial ventilation, suitable
      for application in mono-patient breathing circuits, is described here. The
      sensing element consists of two nominally identical bipolar junction transistors
      employed as hot bodies. The sensor working principle is based on the convective
      heat transfer between the transistors, heated by Joule phenomenon, and the colder
      hitting fluid which represents the measurand. The proposed design allows the
      sensor to discriminate flow direction. Static calibration has been carried out in
      a range of flowrate values (from -8 L.min(-1) up to +8 L L.min(-1)) covering the
      ones employed in neonatal ventilation, at different pipe diameters (ie., 10 mm
      and 30 mm) and collector currents (i.e., 500 mA, 300 mA, and 100 mA) in order to
      assess the influence of these two parameters on sensor's response. Results show
      that the configuration with a pipe diameter of 10 mm at the highest collector
      current guarantees the highest sensitivity (i.e., 763 mV/Lmin1 at low flowrate +/
      1 L-min(-1)) and ensures the minimum dead space (2 mL vs 18 mL for 30 mm of
      diameter). On the other hand, the 30 mm pipe diameter allows extending the range
      of measurement (up to +/-6 L-min 1 vs +/-3.5 L. min(-1) at 10 mm), and improving
      both the discrimination threshold (<;0.1 L.min-(1)) and the symmetry of response.
      These characteristics together with the low dead space and low cost foster its
      application to neonatal ventilation. 

PMID- 25570405
TI  - Instrumentation for the detection and interruption of apnea episodes for
      premature newborn.
AB  - Apnea of prematurity is very frequent in premature newborns (PNB). If the apnea
      episode is not interrupted in time, it can cause several damages to the newborn's
      central nervous system. In this paper, we introduce a novel technology for
      detecting apnea of prematurity episodes, based on cardiac pulse frequency (PF)
      and arterial oxygen saturation (SpO2) simultaneously, and using vibrotactile
      stimulation to interrupt such episodes. The thresholds of the newborns' PF and
      SpO2 had been established to identify the apnea episode automatically through the
      proposed system: for babies <= 35 weeks gestation, PF is <= 100 bpm and SpO2 <=
      80%; for babies > 35 weeks gestation, PF is <= 80 bpm and SpO2 <= 80%. The system
      used vibrotactile stimuli at 250 Hz for 4 s. To manage the system that activates
      the vibratory device automatically and registers those parameters, a program had
      been developed. It registers apnea occurrence, period of manual stimulation and
      vibratory stimulation duration. This technique was tested on 4 PNB. It was
      observed 10 apnea episodes and the device was successful in the detection of all
      of them. The vibrotactile stimulation was capable of promoting the return of
      respiratory movements in 9 of the 10 detected events of apnea and seemed to be a
      promising means of handling them. 

PMID- 25570407
TI  - Measurement of condensed water mass during mechanical ventilation with heated
      wire humidifiers: experiments with and without pre-warming.
AB  - Heated wire humidifiers (HWHs) are employed in mechanical ventilation with the
      objective of heating and humidifying the gases delivered to the mechanical
      ventilator. They use a control based on the adjustment of gas temperature at the
      chamber outlet. The condensation occurring within the breathing circuit is one of
      the most important concerns related to this control strategy. In the present
      study we focused on the measurement of the condensation amount within the
      breathing circuit during the employment of a commercial HWH (MR850, Fisher &
      Paykel). The measurement of the condensed vapor mass, performed during 7 h of
      ventilation, provides more objective information than the visual-based scale used
      in literature. Moreover, two solutions were proposed to minimize the condensation
      in the breathing circuit tract downward the heated chamber: i) a flexible
      insulating pipe was used to cover the mentioned breathing circuit tract, and ii)
      the air delivered by ventilator was heated before it passes through the chamber
      at different inlet temperature Ti obtained by employing pre-warming. To assess
      the improvement obtained by these two solutions, experiments have been carried
      out with and without their employment at two minute volumes. Results show that:
      i) insulation and pre-warming allows minimizing the condensation (e.g., at 8
      L.min(-1) the mass of condensation after 7 h of ventilation decreases from 9.3 g
      to 2.5 g by using insulation and T(i)=27  degrees C); ii) the condensation mass
      decreases with T(i) (e.g., at 8 L.min(-1) the mass condensation was 2.5 g at
      T(i)= 27  degrees C and 1.1 g at T(i)= 30  degrees C); and iii) the amount of
      condensation linearly increases with time of ventilation.

PMID- 25570408
TI  - A novel mainstream capnometer system for polysomnography integrated with
      measurement of nasal pressure and thermal airflow.
AB  - Capnometry is a method to measure carbon dioxide (CO(2)) in exhaled gas and its
      use during polysomnography (PSG) for diagnostic of sleep apnea-hypopnea syndrome
      is expanding. However, some problems exist for using capnometer in combination
      with other respiratory monitoring devices because capnometry requires additional
      sampling cannula or airway adapter attached to patients. To resolve these
      problems, we developed a novel mainstream capnometer system for PSG, which is
      designed to integrate multiple devices for measuring respiratory parameters. This
      system may provide comfortable and stable PSG including capnometry. We evaluated
      the basic performance of this system using a spontaneous breathing model. The
      result indicates that this newly developed system works adequately in PSG and
      moreover has superior characteristics of capnography signal and measurement
      stability against displacement of sensors, compared to conventional devices.

PMID- 25570409
TI  - Optimal voice coil actuators for needle-free jet injection.
AB  - We present a scaling model for electrically-actuated needle free jet injectors,
      establishing the relationship between injection volume and motor size. Using an
      analytical electromagnetic model for the motor, we derive an optimal motor
      design, and show that this design is approximately scale-invariant. To illustrate
      the utility of this model, we then describe the design of a motor for use with
      300 MUL disposable injection ampoules with a mass of just 300 g, including a
      light-weight support structure. Experimental verification of the motor
      performance shows close agreement to model predictions, with a peak force of 1000
      N/kg and a 150 m/s water jet delivered.

PMID- 25570410
TI  - An active brace for controlled transdermal drug delivery for adjustable physical
      therapy.
AB  - This study presents an active brace which is a cost efficient precision
      controlled advanced therapy medicinal product for time and rate controlled
      transdermal drug delivery (TDD) through the use of drug containing nanoparticles
      and electronics. The active brace is designed to adjust the pressure at the
      contact area where the medication is applied. The drug is contained in the
      nanoparticles produced and takes effect when the nanoparticles burst under
      pressure. The brace is designed to be compact and wearable which can be
      preprogrammed by a specialist to continue treatment sessions outside the medical
      facilities providing convenience and comfort to the patient. 

PMID- 25570411
TI  - Mechanism for measurement of flow rate of cerebrospinal fluid in hydrocephalus
      shunts.
AB  - The measurement of the flow rate of cerebrospinal fluid (CSF) or existence of CSF
      flow inside the shunt tube after shunt implant have been reported as tedious
      process for both patients and doctors; this paper outlines a potential in vitro
      flow rate measurement method for CSF in the hydrocephalus shunt. The use of
      implantable titanium elements in the shunt has been proposed to allow for an
      accurate temperature measurement along the shunt for prediction of CSF flow rate.
      The CSF flow velocity can be deduced by decoupling the thermal transfer in the
      measured differential time at a pair of measurement spots of the titanium
      elements. Finite element analyses on the fluidic and thermal behaviors of the
      shunt system have been conducted. Preliminary bench-top measurements on a
      simulated system have been carried out. The measured flow rates, ranging from 0.5
      mm/sec to 1.0 mm/sec, which is clinically practical, demonstrate good agreements
      with the simulation results. 

PMID- 25570412
TI  - Control of a thin catheter bending at bifurcation points in artificial blood
      vessel by using acoustic radiation force.
AB  - In this paper, control of a thin catheter bending by using acoustic radiation
      force was carried out to develop precise and noninvasive surgery in small blood
      vessel. First, it was elucidated that the acting force to a thin catheter made
      from perfluoroalkoxy (PFA) copolymer could be obtained from the cantilever
      equation in the effective range, where the displacement of the catheter divided
      by the cube of the length of the catheter was less than 1.0*10(-5) mm(-2). Next,
      under the above cantilever theory, acoustic radiation force acting to the
      catheter was measured in the condition of the continuous ultrasound radiation.
      Furthermore, it was observed that the force depended on the ultrasound frequency.
      We confirmed that the force was obtained in the practical condition by the
      experiment and controlled it bending in artificial blood vessel including
      multiple bifurcations. It was suggested that the therapy using thin catheter and
      ultrasound is fully promising. 

PMID- 25570413
TI  - A programmable point-of-care device for external CSF drainage and monitoring.
AB  - This paper presents a prototype of a programmable cerebrospinal fluid (CSF)
      external drainage system that can accurately measure the dispensed fluid volume.
      It is based on using a miniature spectrophotometer to collect color data to
      inform drain rate and pressure monitoring. The prototype was machined with 1 MUm
      dimensional accuracy. The current device can reliably monitor the total
      accumulated fluid volume, the drain rate, the programmed pressure, and the
      pressure read from the sensor. Device requirements, fabrication processes, and
      preliminary results with an experimental set-up are also presented. 

PMID- 25570414
TI  - Systematic diagnosis of prostate cancer using an optical biopsy needle adjunct
      with fluorescence spectroscopy.
AB  - Transrectal ultrasound guided prostate biopsies often fail to diagnose prostate
      cancer with 90% of cores reported as benign. Thus, it is desirable to target
      prostate cancer lesions while reducing the sampling of benign tissue. The
      concentrations of natural fluorophores in prostate tissue fluctuate with disease
      states. Hence, fluorescence spectroscopy could be used to quantify these
      fluctuations to identify prostate cancer. An optical biopsy needle with a light
      sensitive optical probe at the tip of the inner needle was developed to take
      prostate biopsies after measuring tissue fluorescence with a laboratory
      fluorometer. The optical probe consists of eight 100 MUm fibers for tissue
      excitation and a single 200 MUm fiber to capture fluorescence spectra. Random
      biopsy cores were taken from 20 surgically excised prostates after measuring
      fluorescence spectra of tissue between 295-550nm for several excitations between
      280-350nm. Each biopsy core was histopathologically classified and correlated
      with corresponding spectra. Prostate biopsies were grouped into benign or
      malignant based on the histological findings. Out of 187 biopsy cores, 109 were
      benign and 78 were malignant. Partial least square analysis of tissue spectra was
      performed to identify diagnostically significant principal components as
      potential classifiers. A linear support vector machine and leave-one-out cross
      validation method was employed for tissue classification. Study results show 86%
      sensitivity, 87% specificity, 90% negative predictive value, and 83% positive
      predictive value for benign versus malignant prostate tissue classification. This
      study demonstrates potential clinical applications of fluorescence spectroscopy
      guided optical biopsy needle for prostate cancer diagnosis with the consequent
      improvement of patient care. 

PMID- 25570415
TI  - Development of Android apps for cognitive assessment of dementia and delirium.
AB  - The next generation of medical technology applications for hand-held portable
      platforms will provide a core change in performance and sophistication,
      transforming the way health care professionals interact with patients. This
      advance is particularly apparent in the delivery of cognitive patient
      assessments, where smartphones and tablet computers are being used to assess
      complex neurological conditions to provide objective, accurate and reproducible
      test results. This paper reports on two such applications (apps) that have been
      developed to assist healthcare professionals with the detection and diagnosis of
      dementia and delirium. 

PMID- 25570416
TI  - Smart watch RSSI localization and refinement for behavioral classification using
      laser-SLAM for mapping and fingerprinting.
AB  - As a first step toward building a smart home behavioral monitoring system capable
      of classifying a wide variety of human behavior, a wireless sensor network (WSN)
      system is presented for RSSI localization. The low-cost, non-intrusive system
      uses a smart watch worn by the user to broadcast data to the WSN, where the
      strength of the radio signal is evaluated at each WSN node to localize the user.
      A method is presented that uses simultaneous localization and mapping (SLAM) for
      system calibration, providing automated fingerprinting associating the radio
      signal strength patterns to the user's location within the living space. To
      improve the accuracy of localization, a novel refinement technique is introduced
      that takes into account typical movement patterns of people within their homes.
      Experimental results demonstrate that the system is capable of providing accurate
      localization results in a typical living space. 

PMID- 25570417
TI  - A smartphone based ophthalmoscope.
AB  - A low-cost alternative to the direct ophthalmoscope, a simple optical adapter for
      a smartphone, is described. It can overcome many of the technical challenges of
      fundoscopy, providing a high-resolution view of the retina through an un-dilated
      pupil. This can be used in locations with limited diagnostic resources to detect
      conditions such as glaucomatous optic neuropathy. Comparison of optic nerve
      images from commercial retinal screening cameras with the smartphone adapter
      demonstrates strong evidence for no difference in performance in glaucomatous
      disc grading (p=0.98, paired student t test, n=300). 

PMID- 25570418
TI  - Smart phone monitoring of second heart sound split.
AB  - Heart Auscultation (listening to heart sounds) is the basic element of cardiac
      diagnosis. The interpretation of these sounds is a difficult skill to acquire. In
      this work we have developed an application to detect, monitor, and analyze the
      split in second heart sound (S2) using a smart phone. The application records the
      heartbeat using a stethoscope connected to the smart phone. The audio signal is
      converted into the frequency domain using Fast Fourier Transform to detect the
      first and second heart sounds (S1 and S2). S2 is extracted and fed into the
      Discrete Wavelet Transform (DWT) and then to Continuous Wavelet Transform (CWT)
      to detect the Aortic (A2) and the Pulmonic (P2) components, which are used to
      calculate the split in S2. With our application, users can continuously monitor
      their second heart sound irrespective of ages and check for a split in their
      hearts with a low-cost, easily available equipment. 

PMID- 25570419
TI  - Assessment of visual impairment in stroke survivors.
AB  - A novel, tablet-based application (app) has been developed to act as a screening
      tool for visual impairment in stroke survivors; The Stroke Vision app. The app
      includes assessments for visual acuity, visual fields and visuospatial neglect,
      as well as novel tools for the education of patients, carers and staff. The app
      has been devised by experts in the field to address two important deficiencies;
      firstly a set of visual assessment tools to support and improve evaluation and
      rehabilitation of visual impairments in stroke survivors, and secondly to provide
      education for staff and information to carers about their relatives visual
      disabilities. 

PMID- 25570421
TI  - Power spectrum of the rectified EMG: influence of motor unit action potential
      shapes.
AB  - The rectification of EMG signals is a preprocessing method widely used for
      inferring neural connectivity by coherence analysis. The assumption for the use
      of this non-linear operator is that it enhances the neural information in the
      signal, i.e. the motor unit spike trains. However, because of non-linearity, it
      is difficult to predict the effect of rectification on the EMG power spectrum. In
      this study, we analyze the influence of the motor unit action potential
      properties on spectral content of the rectified EMG. The results show that
      changes in the action potential waveforms have a strong influence on the
      rectified EMG power spectrum, with an effect on estimated coherence functions.
      Knowledge on the properties of action potentials may be necessary for properly
      comparing the rectified EMG power spectrum across conditions. 

PMID- 25570420
TI  - New mobile technologies and visual acuity.
AB  - Mobile devices have shown promise in visual assessment. Traditional acuity
      measurement involves retro-illuminated charts or card-based modalities. Mobile
      platforms bring potential to improve on both portability and objectivity. The
      present research activity relates to design and validation of a novel tablet
      based infant acuity test. Early results in an adult cohort, with various levels
      of artificially degraded vision, suggest improved test-retest reliability
      compared with current standards for infant acuity. Future pragmatic trials will
      assess the value of this emerging technology in pediatric visual screening. 

PMID- 25570422
TI  - Spectral analysis of resting state magnetoencephalogram activity in patients with
      bipolar disorder.
AB  - We analyzed the frequency spectrum of magnetoencephalogram (MEG) background
      activity in 16 bipolar disorder (BD) patients and 24 age-matched healthy control.
      Median frequency (MF), spectral entropy (SpEn), and relative power in delta
      (RPdelta), theta (RPtheta), alpha (RPalpha), beta (RPbeta), and gamma (RPgamma)
      bands were computed for all 148 MEG channels. Significant differences between the
      two groups were found in the average level of MF, RPdelta, and RPtheta in the
      posterior region of the scalp. Moreover, the MF, SpEn, RPdelta, and RPbeta values
      of BD patients had a different dependence on age as compared with the results of
      control subjects, which may suggest that BD affects how the brain activity
      develops with age. We conclude that the spectral analysis of the background MEG
      in BD patients may give insights into how this condition affects the brain
      activity. 

PMID- 25570423
TI  - Evaluation of Laplacian diaphragm electromyographic recording in a dynamic
      inspiratory maneuver.
AB  - The analysis of the electromyographic signal of the diaphragm muscle (EMGdi) can
      provide important information for evaluating the respiratory muscular function.
      The EMGdi can be recorded using surface Ag/AgCl disc electrodes in monopolar or
      bipolar configuration. However, these non-invasive EMGdi recordings are usually
      contaminated by the electrocardiographic (ECG) signal. EMGdi signal can also be
      noninvasively recorded using concentric ring electrodes in bipolar configuration
      (CRE) that estimate Laplacian surface potential. Laplacian recordings increase
      spatial resolution and attenuate distant bioelectric interferences, such as the
      ECG. Thus, the objective of this work is to compare and to evaluate CRE and
      traditional bipolar EMGdi recordings in a healthy subject during a dynamic
      inspiratory maneuver with incremental inspiratory loads. In the conducted study,
      it was calculated the cumulative percentage of power spectrum of EMGdi recordings
      to determine the signal bandwidth, and the power ratio between the EMGdi signal
      segments with and without cardiac activity. The results of this study suggest
      that EMGdi acquired with CRE electrodes is less affected by the ECG interference,
      achieves a wider bandwidth and a higher power ratio between segments without
      cardiac activity and with cardiac activity. 

PMID- 25570424
TI  - Surface electromyogram-based detection of muscle fatigue during cyclic dynamic
      contraction under blood flow restriction.
AB  - Surface electromyogram (SEMG) measurements employing a bipolar configuration are
      generally used to evaluate muscle fatigue. However, the changes in the SEMGs
      accompanying fatigue cannot be detected in some cases. We evaluated the
      differences in the detection of muscle fatigue during isometric and dynamic
      contraction between monopolar and bipolar configurations for measuring SEMGs. The
      results illustrated that the monopolar configuration is well suited for detecting
      waves slowed by muscle fatigue. In this study, the effectiveness of the monopolar
      configuration during dynamic contraction under blood flow restriction was
      verified. Our findings suggested that the monopolar configuration can detect
      changes in muscle fatigue with greater sensitivity than the bipolar configuration
      even under blood flow restriction. 

PMID- 25570425
TI  - Evaluation of HD-sEMG Probability Density Function deformations in ramp exercise.
AB  - The aim of the present study is to propose a subject-specific screening approach
      of High Density surface EMG (HD-sEMG) Probability Density Function (PDF) shape
      evolution in experimental conditions following a ramp exercise from 0% to 50% of
      the Maximum Voluntary Contraction (MVC) during 25 seconds of isometric
      contractions of the Biceps Brachii from six healthy subjects. This method uses
      High Order Statistics (HOS), namely the kurtosis and the skewness for PDF shape
      screening examined on selectively positioned Laplacian sEMG channels obtained on
      an 8*8 HD-sEMG grid. For each subject, the position of the Laplacian channels was
      chosen based on the level of muscle activation obtained from the Signal to Noise
      Ratio (SNR) matrix computed for the 64 sEMG signals of the grid in order to
      obtain independent Laplacian configurations localized in areas with high SNRs
      indicating high muscle activation. Afterwards, we used the Principal Component
      Analysis (PCA) to obtain the principal trend of the kurtosis and the skewness
      computed from the selected Laplacian signals according to force level variation.
      The obtained results show a globally common increasing HOS trend according to
      force increase from 0% to 50% MVC for all the subjects regardless of the
      anatomical, instrumental and physiological variability that usually strongly
      influences these trends. 

PMID- 25570426
TI  - Robust functional statistics applied to Probability Density Function shape
      screening of sEMG data.
AB  - Recent studies pointed out possible shape modifications of the Probability
      Density Function (PDF) of surface electromyographical (sEMG) data according to
      several contexts like fatigue and muscle force increase. Following this idea,
      criteria have been proposed to monitor these shape modifications mainly using
      High Order Statistics (HOS) parameters like skewness and kurtosis. In
      experimental conditions, these parameters are confronted with small sample size
      in the estimation process. This small sample size induces errors in the estimated
      HOS parameters restraining real-time and precise sEMG PDF shape monitoring.
      Recently, a functional formalism, the Core Shape Model (CSM), has been used to
      analyse shape modifications of PDF curves. In this work, taking inspiration from
      CSM method, robust functional statistics are proposed to emulate both skewness
      and kurtosis behaviors. These functional statistics combine both kernel density
      estimation and PDF shape distances to evaluate shape modifications even in
      presence of small sample size. Then, the proposed statistics are tested, using
      Monte Carlo simulations, on both normal and Log-normal PDFs that mimic observed
      sEMG PDF shape behavior during muscle contraction. According to the obtained
      results, the functional statistics seem to be more robust than HOS parameters to
      small sample size effect and more accurate in sEMG PDF shape screening
      applications. 

PMID- 25570427
TI  - Impact of head modeling and sensor types in localizing human gamma-band
      oscillations.
AB  - An effective mechanism in neuronal communication is oscillatory neuronal
      synchronization. The neuronal gamma-band (30-100 Hz) synchronization is
      associated with attention which is induced by a certain visual stimuli. Numerous
      studies have shown that the gamma-band activity is observed in the visual cortex.
      However, impact of different head modeling techniques and sensor types to
      localize gamma-band activity have not yet been reported. To do this, the brain
      activity was recorded using 306 magnetoencephalography (MEG) sensors, consisting
      of 102 magnetometers and 102 pairs of planar gradiometers (one measuring the
      derivative of the magnetic field along the latitude and the other along the
      longitude), and the data were analyzed with respect to time, frequency, and
      location of the strongest response. The spherical head models with a single-shell
      and overlapping spheres (local sphere) have been used as a forward model for
      calculating the external magnetic fields generated from the gamma-band activity.
      For each sensor type, the subject-specific frequency range of the gamma-band
      activity was obtained from the spectral analysis. The identified frequency range
      of interest with the highest gamma-band activity is then localized using a
      spatial-filtering technique known as dynamic imaging of coherent sources (DICS).
      The source analysis for all the subjects revealed that the gradiometer sensors
      which measure the derivative along the longitude, showed sources close to the
      visual cortex (cuneus) as compared to the other gradiometer sensors which measure
      the derivative along the latitude. However, using the magnetometer sensors, it
      was not possible to localize the sources in the region of interest. When
      comparing the two head models, the local-sphere model helps in localizing the
      source more focally as compared to the single-shell head model. 

PMID- 25570428
TI  - Automated Sleep Spindle detection using novel EEG features and mixture models.
AB  - Research in automated Sleep Spindle detection has been highly explored in the
      past few years. Although a number of automated techniques were developed, many of
      them were based on using fixed parameters or thresholds which do not consider
      subject specific differences. In this research study, we introduce a novel method
      of sleep spindle detection using Gaussian Mixture Models with no fixed parameters
      or thresholds. The algorithm was tested on an online public spindles database
      consisting of six 30 minute sleep excerpts extracted from whole night recordings
      of 6 subjects. The results obtained were better when compared with other methods.
      We obtained an overall sensitivity of 74.9% at a 28% False Positive proportion. 

PMID- 25570429
TI  - Optimizing dynamical similarity index extraction window for seizure detection.
AB  - This paper addresses an optimization problem in choosing optimum window length
      for feature extraction in automatic seizure detection. The processing window
      length plays an important role in reducing the false positive and false negative
      rates and decreasing required processing time for seizure detection. This study
      presents an approach for selecting the optimum window length toward the
      extraction of dynamical similarity index (DSI) feature. Then, the optimal window
      value in DSI extraction was used to detect seizure onset automatically. The
      algorithm was applied to electroencephalogram (EEG) signals from European
      Epilepsy Database. Although the main purpose of this study was not the seizure
      detection and mainly focuses on proposing an approach for finding an optimum
      window length for feature extraction towards the early seizure detection, the
      results showed that the proposed method achieves 83.99% of sensitivity in seizure
      detection. The low false positive rate per hour (FPR/h) was also significant due
      to continuous EEG analysis. The method showed fast computation speed which
      promises a potential for the real time applications. The proposed method for the
      window optimization in feature extraction of DSI can be implemented for other
      features to further improve the performance of seizure detection. 

PMID- 25570430
TI  - Quantitative assessments of arousal by analyzing microsaccade rates and pupil
      fluctuations prior to slow eye movements.
AB  - It is well known that a decline of arousal level causes of poor performance of
      movements or judgments. Our previous study indicates that microsaccade (MS) rates
      and pupil fluctuations change before slow eye movements (SEMs) (Honda et al.
      2013). However, SEM detection of this study was obscure and insufficient. In this
      study, we propose a new SEM detection method and analyze MS rates and pupil
      fluctuations while subjects maintain their gaze on a target. We modified Shin et
      al.'s method, which is optimized for EOG (electrooculography) signals, to extract
      the period of sustaining SEMs using a general eye tracker. After SEM detection,
      we analyzed MS rates and pupil fluctuations prior to the initiation of SEMs. As a
      result, we were able to detect SEMs more precisely than in our previous study.
      Moreover, the results of eye movements and pupil fluctuations analyses show that
      gradual rise of MS rate and longitudinal miosis are observed prior to the
      initiation of SEMs, which is consistent with our previous study. These findings
      suggest that monitoring eye movements and pupil fluctuations may evaluate the
      arousal level more precisely. Further, we found that these tendencies become more
      significant when they are restricted to the initial SEMs. 

PMID- 25570431
TI  - Signal quality quantification and waveform reconstruction of arterial blood
      pressure recordings.
AB  - Arterial blood pressure (ABP) is an important vital sign of the cardiovascular
      system. As with other physiological signals, its measurement can be corrupted by
      different sources of noise, interference, and artifact. Here, we present an
      algorithm for the quantification of signal quality and for the reconstruction of
      the ABP waveform in noise-corrupted segments of the measurement. The algorithm
      quantifies the quality of the ABP signal on a beat-by-beat basis by computing the
      normalized mean of successive differences of the ABP amplitude over each beat. In
      segments of poor signal quality, the ABP wavelets are then reconstructed on the
      basis of the expected cycle duration and envelope information derived from
      neighboring ABP wavelet segments. The algorithm was tested on two datasets of ABP
      waveform signals containing both invasive radial artery ABP and noninvasive ABP
      waveforms. Our results show that the approach is efficient in identifying the
      noisy segments (accuracy, sensitivity and specificity over 95%) and reliable in
      reconstructing beats that were artificially corrupted. 

PMID- 25570432
TI  - Macro-motion detection using ultra-wideband impulse radar.
AB  - Radar has the advantage of being able to detect hidden individuals, which can be
      used in homeland security, disaster rescue, and healthcare monitoring-related
      applications. Human macro-motion detection using ultra-wideband impulse radar is
      studied in this paper. First, a frequency domain analysis is carried out to show
      that the macro-motion yields a bandpass signal in slow-time. Second, the FTFW
      (fast-time frequency windowing), which has the advantage of avoiding the
      measuring range reduction, and the HLF (high-pass linear-phase filter), which can
      preserve the motion signal effectively, are proposed to preprocess the radar
      echo. Last, a threshold decision method, based on the energy detector structure,
      is presented. 

PMID- 25570433
TI  - Spectrum-averaged Harmonic Path (SHAPA) algorithm for non-contact vital sign
      monitoring with ultra-wideband (UWB) radar.
AB  - We introduce the Spectrum-averaged Harmonic Path (SHAPA) algorithm for estimation
      of heart rate (HR) and respiration rate (RR) with Impulse Radio Ultrawideband (IR
      UWB) radar. Periodic movement of human torso caused by respiration and heart beat
      induces fundamental frequencies and their harmonics at the respiration and heart
      rates. IR-UWB enables capture of these spectral components and frequency domain
      processing enables a low cost implementation. Most existing methods of
      identifying the fundamental component either in frequency or time domain to
      estimate the HR and/or RR lead to significant error if the fundamental is
      distorted or cancelled by interference. The SHAPA algorithm (1) takes advantage
      of the HR harmonics, where there is less interference, and (2) exploits the
      information in previous spectra to achieve more reliable and robust estimation of
      the fundamental frequency in the spectrum under consideration. Example
      experimental results for HR estimation demonstrate how our algorithm eliminates
      errors caused by interference and produces 16% to 60% more valid estimates. 

PMID- 25570434
TI  - Estimation of body temperature rhythm based on heart activity parameters in daily
      life.
AB  - Body temperature contains valuable health related information such as circadian
      rhythm and menstruation cycle. Also, it was discovered from previous studies that
      body temperature rhythm in daily life is related with sleep disorders and
      cognitive performances. However, monitoring body temperature with existing
      devices during daily life is not easy because they are invasive, intrusive, or
      expensive. Therefore, the technology which can accurately and nonintrusively
      monitor body temperature is required. In this study, we developed body
      temperature estimation model based on heart rate and heart rate variability
      parameters. Although this work was inspired by previous research, we originally
      identified that the model can be applied to body temperature monitoring in daily
      life. Also, we could find out that normalized Mean heart rate (nMHR) and
      frequency domain parameters of heart rate variability showed better performance
      than other parameters. Although we should validate the model with more number of
      subjects and consider additional algorithms to decrease the accumulated
      estimation error, we could verify the usefulness of this approach. Through this
      study, we expect that we would be able to monitor core body temperature and
      circadian rhythm from simple heart rate monitor. Then, we can obtain various
      health related information derived from daily body temperature rhythm. 

PMID- 25570435
TI  - Relation between heart beat fluctuations and cyclic alternating pattern during
      sleep in insomnia patients.
AB  - Insomnia is a condition that affects the nervous and muscular system. Thirty
      percent of the population between 18 and 60 years suffers from insomnia. The
      effects of this disorder involve problems such as poor school or job performance
      and traffic accidents. In addition, patients with insomnia present changes in the
      cardiac function during sleep. Furthermore, the structure of
      electroencephalographic A-phases, which builds up the Cyclic Alternating Pattern
      during sleep, is related to the insomnia events. Therefore, the relationship
      between these brain activations (A-phases) and the autonomic nervous system would
      be of interest, revealing the interplay of central and autonomic activity during
      insomnia. With this goal, a study of the relationship between A-phases and heart
      rate fluctuations is presented. Polysomnography recording of five healthy
      subjects, five sleep misperception patients and five patients with
      psychophysiological insomnia were used in the study. Detrended Fluctuation
      Analysis (DFA) was used in order to evaluate the heart rate dynamics and this was
      correlated with the number of A-phases. The results suggest that pathological
      patients present changes in the dynamics of the heart rate. This is reflected in
      the modification of A-phases dynamics, which seems to modify of heart rate
      dynamics. 

PMID- 25570436
TI  - On separability of A-phases during the cyclic alternating pattern.
AB  - A statistical analysis of the separability of EEG A-phases, with respect to basal
      activity, is presented in this study. A-phases are short central events that
      build up the Cyclic Alternating Pattern (CAP) during sleep. The CAP is a brain
      phenomenon which is thought to be related to the construction, destruction and
      instability of sleep stages dynamics. From the EEG signals, segments obtained
      around the onset and offset of the A-phases were used to evaluate the
      separability between A-phases and basal sleep stage oscillations. In addition, a
      classifier was trained to separate the different A-phase types (A1, A2 and A3).
      Temporal, energy and complexity measures were used as descriptors for the
      classifier. The results show a percentage of separation between onset and
      preceding basal oscillations higher than 85 % for all A-phases types. For Offset
      separation from following baseline, the accuracy is higher than 80 % but
      specificity is around 75%. Concerning to A-phase type separation, A1-phase and A3
      phase are well separated with accuracy higher than 80, while A1 and A2-phases
      show a separation lower than 50%. These results encourage the design of automatic
      classifiers for Onset detection and for separating among A-phases type A1 and A3.
      On the other hand, the A-phase Offsets present a smooth transition towards the
      basal sleep stage oscillations, and A2-phases are very similar to A1-phases,
      suggesting that a high uncertainty may exist during CAP annotation. 

PMID- 25570437
TI  - Oxygen saturation resolution influences regularity measurements.
AB  - The measurement of regularity in the oxygen saturation (SpO(2)) signal has been
      suggested for use in identifying subjects with sleep disordered breathing (SDB).
      Previous work has shown that children with SDB have lower SpO(2) regularity than
      subjects without SDB (NonSDB). Regularity was measured using non-linear methods
      like approximate entropy (ApEn), sample entropy (SamEn) and Lempel-Ziv (LZ)
      complexity. Different manufacturer's pulse oximeters provide SpO(2) at various
      resolutions and the effect of this resolution difference on SpO(2) regularity,
      has not been studied. To investigate this effect, we used the SpO(2) signal of
      children with and without SDB, recorded from the Phone Oximeter (0.1% resolution)
      and the same SpO(2) signal rounded to the nearest integer (artificial 1%
      resolution). To further validate the effect of rounding, we also used the SpO(2)
      signal (1% resolution) recorded simultaneously from polysomnography (PSG), as a
      control signal. We estimated SpO(2) regularity by computing the ApEn, SamEn and
      LZ complexity, using a 5-min sliding window and showed that different resolutions
      provided significantly different results. The regularity calculated using 0.1%
      SpO(2) resolution provided no significant differences between SDB and NonSDB.
      However, the artificial 1% resolution SpO(2) provided significant differences
      between SDB and NonSDB, showing a more random SpO(2) pattern (lower SpO(2)
      regularity) in SDB children, as suggested in the past. Similar results were
      obtained with the SpO(2) recorded from PSG (1% resolution), which further
      validated that this SpO(2) regularity change was due to the rounding effect.
      Therefore, the SpO(2) resolution has a great influence in regularity measurements
      like ApEn, SamEn and LZ complexity that should be considered when studying the
      SpO(2) pattern in children with SDB.

PMID- 25570438
TI  - Investigating foetal heart rate asymmetry.
AB  - In this study, we have investigated how the asymmetry of beat-to-beat foetal
      heart rate variability (fHRV) changes during development after 35 weeks and
      before 32 weeks of gestation. Noninvasive foetal electrocardiogram (fECG) signals
      from 78 pregnant women at the gestational age from 16 to 41 weeks with normal
      single pregnancies were analysed. Heart rate asymmetry (HRA) index that measures
      time asymmetry of RR interval time-series signal was used to understand the
      dynamics of fHRV. Results indicate that foetal HRA measured by Guzik's Index (GI)
      and Porta's Index (PI) changes after 35 weeks gestation compared to foetus before
      32 weeks of gestation. It might be due to significant amount of maturation of the
      autonomic nervous system done after 35 and could potentially help identify the
      pathological autonomic nervous system development. 

PMID- 25570439
TI  - Automatic sleep onset detection using single EEG sensor.
AB  - Sleep has been shown to be imperative for the health and well-being of an
      individual. To design intelligent sleep management tools, such as the music
      induce sleep-aid device, automatic detection of sleep onset is critical. In this
      work, we propose a simple yet accurate method for sleep onset prediction, which
      merely relies on Electroencephalogram (EEG) signal acquired from a single frontal
      electrode in a wireless headband. The proposed method first extracts energy power
      ratio of theta (4-8Hz) and alpha (8-12Hz) bands along a 3-second shifting window,
      then calculates the slow wave of each frequency band along the time domain. The
      resulting slow waves are then fed to a rule-based engine for sleep onset
      detection. To evaluate the effectiveness of the approach, polysomnographic (PSG)
      and headband EEG signals were obtained from 20 healthy adults, each of which
      underwent 2 sessions of sleep events. In total, data from 40 sleep events were
      collected. Each recording was then analyzed offline by a PSG technologist via
      visual observation of PSG waveforms, who annotated sleep stages N1 and N2 by
      using the American Academy of Sleep Medicine (AASM) scoring rules. Using this as
      the gold standard, our approach achieved a 87.5% accuracy for sleep onset
      detection. The result is better or at least comparable to the other state of the
      art methods which use either multi-or single- channel based data. The approach
      has laid down the foundations for our future work on developing intelligent sleep
      aid devices. 

PMID- 25570440
TI  - P and T wave detection on multichannel ECG using FRI.
AB  - This paper proposes a new method for detecting P and T waves in multilead ECG
      based on the Finite Rate of Innovation(FRI) technique [8]. A simple QRS detection
      scheme will be presented followed by a novel P and T wave detection algorithm.
      The novelty here is the modelling of the P and T wave using a Gaussian kernel.
      Using a 2D wavelet decomposition, the approximation coefficients are windowed
      based on the QRS locations. The FRI method is then used to identify the Gaussian
      distribution present in the window which will in turn provide the locations of
      the P and T wave. This method was tested on more than an hour of clean and noisy
      data and shows good performance in the noisy case. 

PMID- 25570441
TI  - Computationally efficient QRS detection analysis based on dual-slope method.
AB  - This paper presents a computationally efficient QRS detection algorithm for
      wearable electrocardiogram (ECG) applications based on dual-slope analysis. In
      general, ECG signals of arrhythmias are pseudo-periodic and contaminated with
      noises like the patient's contraction muscles, respiration, 60 Hz interference
      and other types which impede correct QRS detection. To resolve this problem, in
      this paper, a technique is presented which is based on two slopes on both sides
      of a peak in ECG signal. Based on these slopes, a variable measuring steepness is
      developed and R peaks are detected. The algorithm was evaluated against MIT/BIH
      arrhythmia database and achieved 99.38% detection rate. This method was compared
      with one of the recently developed dual-slope based QRS detection methods. The
      results showed that the proposed method has 12.48 times faster runtime than the
      old method. 

PMID- 25570442
TI  - Ambulatory estimation of human circadian phase using models of varying complexity
      based on non-invasive signal modalities.
AB  - In this work, we introduce a number of models for human circadian phase
      estimation in ambulatory conditions using various sensor modalities. Machine
      learning techniques have been applied to ambulatory recordings of wrist
      actigraphy, light exposure, electrocardiograms (ECG), and distal and proximal
      skin temperature to develop ARMAX models capturing the main signal dependencies
      on circadian phase and evaluating them versus melatonin onset times. The most
      accurate models extracted heart rate variability features from an ECG coupled
      with wrist activity information to produce phase estimations with prediction
      errors of ~30 minutes. Replacing the ECG features with skin temperature from the
      upper leg led to a slight degradation, while less accurate results, in the order
      of 1 hour, were obtained from wrist activity and light measurements. The trade
      off between highest precision and least obtrusive configuration is discussed for
      applications to sleep and mood disorders caused by a misalignment of the internal
      phase with the external solar and social times. 

PMID- 25570443
TI  - ECG-derived respirations based on phase-space reconstruction of single-lead ECG:
      validations over various physical activities based on parallel recordings of ECG,
      respiration, and body accelerations.
AB  - ECG derived respiration (EDR) provides a comfortable measurement of respiration
      and is recently applied to sleep studies. Nevertheless, the mechanic disturbances
      due to postural changes or other physical activity during long-term recording is
      less investigated. In the present study, ECG, impedance-based respiration, and
      body accelerations were parallel recorded during a series of scheduled postures
      in 8 healthy subjects and during 24 hours in one subject. In addition, a novel
      EDR method based on phase space reconstruction of single-lead ECG is also
      proposed. The area under major portrait radius (MPR) curve is employed to
      quantify the deviation of phase-space loop which is related to respiration.
      Coherence analysis between the EDR and the impedance-based respiration
      demonstrated that the MPR-based EDR had better performance than using R peak or
      QRS area as the EDR feature in the scheduled postures. 

PMID- 25570445
TI  - Electrodermal activity processing: a convex optimization approach.
AB  - This paper reports on a novel model based on convex optimization methods for the
      analysis of the skin conductance (SC) as response of the electrodermal activity
      (EDA) to affective stimuli. Starting from previous assessed methodological
      approaches, this new model proposes a decomposition of SC into tonic and phasic
      components through the solution of a convex optimization problem. Previous
      knowledge about the physiology of the EDA is accounted for by means of an
      appropriate choice of constraints and regularizers. In order to test the
      effectiveness of the new approach, an experimental session in which 9 healthy
      subjects were stimulated using affective pictures gathered from the IAPS database
      was designed and carried out. The experimental session included series of
      negative-valence high-arousal images and series of neutral images, with an inter
      stimulus interval of about 2 seconds for both neutral and high arousal pictures.
      Next, a statistical analysis was performed on a set of features extracted from
      the phasic driver and the tonic signal estimated by the model. Results showed
      that the phasic driver extracted from the model was able to strongly distinguish
      arousal sessions from neutral ones. Conversely, no significant difference was
      found for the tonic components. This experimental findings are consistent with
      the literature and confirm that the phasic component is strictly related to
      changes in the sympathetic activity of the autonomic nervous system. Although
      preliminary, these results are very encouraging and future work will progress to
      further validate the model through specific and controlled experiments. 

PMID- 25570444
TI  - BioWatch - a wrist watch based signal acquisition system for physiological
      signals including blood pressure.
AB  - A wrist watch based system, which can measure electrocardiogram (ECG) and
      photoplethysmogram (PPG), is presented in this work. By using both ECG and PPG we
      also measure pulse transit time (PTT), which studies show to correlate well with
      blood pressure (BP). The system is also capable of monitoring heart rate using
      either ECG or PPG and can monitor blood oxygenation by easily replacing the PPG
      sensors with a different set. In this work, we investigate methods to train a
      fitting function to convert a PTT measurement to its corresponding systolic BP.
      We also validate measurements on different postures and show the value of
      calibrating the device for each posture. This system, called BioWatch, can
      potentially facilitate continuous and ubiquitous monitoring of ECG, PPG, heart
      rate, blood oxygenation and BP. 

PMID- 25570446
TI  - Automatic heart sound segmentation and murmur detection in pediatric
      phonocardiograms.
AB  - The digital analysis of heart sounds has revealed itself as an evolving field of
      study. In recent years, numerous approaches to create decision support systems
      were attempted. This paper proposes two novel algorithms: one for the
      segmentation of heart sounds into heart cycles and another for detecting heart
      murmurs. The segmentation algorithm, based on the autocorrelation function to
      find the periodic components of the PCG signal had a sensitivity and positive
      predictive value of 89.2% and 98.6%, respectively. The murmur detection algorithm
      is based on features collected from different domains and was evaluated in two
      ways: a random division between train and test set and a division according to
      patients. The first returned sensitivity and specificity of 98.42% and 97.21%
      respectively for a minimum error of 2.19%. The second division had a far worse
      performance with a minimum error of 33.65%. The operating point was chosen at
      sensitivity 69.67% and a specificity 46.91% for a total error of 38.90% by
      varying the percentage of segments classified as murmurs needed for a positive
      murmur classification. 

PMID- 25570447
TI  - Exploring the spectral information of airflow recordings to help in pediatric
      Obstructive Sleep Apnea-Hypopnea Syndrome diagnosis.
AB  - This work aims at studying the usefulness of the spectral information contained
      in airflow (AF) recordings in the context of Obstructive Sleep Apnea-Hypopnea
      Syndrome (OSAHS) in children. To achieve this goal, we defined two spectral bands
      of interest related to the occurrence of apneas and hypopneas. We characterized
      these bands by extracting six common spectral features from each one. Two out of
      the 12 features reached higher diagnostic ability than the 3% oxygen desaturation
      index (ODI3), a clinical parameter commonly used as screener for OSAHS.
      Additionally, the stepwise logistic regression (SLR) feature-selection algorithm
      showed that the information contained in the two bands was complementary, both
      between them and with ODI3. Finally, the logistic regression method involving
      spectral features from the two bands, as well as ODI3, achieved high diagnostic
      performance after a bootstrap validation procedure (84.6+/-9.6 sensitivity,
      87.2+/-9.1 specificity, 85.8+/-5.2 accuracy, and 0.969+/-0.03 area under ROC
      curve). These results suggest that the spectral information from AF is helpful to
      detect OSAHS in children. 

PMID- 25570448
TI  - Similarities of arterial collagen pressure-diameter relationship in ovine femoral
      arteries and PLLA vascular grafts.
AB  - INTRODUCTION: In-vivo implanted vascular grafts fail due to the mechanical
      mismatch between the native vessel and the implant. The biomechanical
      characterization of native vessels provides valuable information towards the
      development of synthetic grafts. MATERIALS AND METHODS: Five samples of
      electrospun nanofibrous poly(L-lactic acid)(PLLA) tubular structures were
      subjected to physiological pulsating pressure using an experimental setup. Four
      ovine femoral arteries were also tested in the experimental setup under the same
      conditions. Instantaneous diameter and pressure signals were obtained using gold
      standard techniques, in order to estimate the dynamic pressure-strain elastic
      modulus (E(Pepsilon)) of both native vessels and grafts. RESULTS: Synthetic
      grafts showed a significant increase of E(Pepsilon) (10.57+/-0.97 to 17.63+/-2.61
      10(6) dyn/cm(2)) when pressure was increased from a range of 50-90 mmHg (elastin
      response range) to a range of 100-130 mmHg (collagen-response range).
      Furthermore, femoral arteries also exhibited a significant increase of EPepsilon
      (1.66+/-0.30 to 15.76+/-4.78 10(6) dyn/cm(2)) with the same pressure variation,
      showing that both native vessels and synthetic grafts have a similar behavior in
      the collagen-acting range. CONCLUSION: The mechanical behavior of PLLA vascular
      grafts was characterized In vitro. However, the procedure can be easily
      extrapolated to In vivo experiences in conscious and chronically instrumented
      animals.

PMID- 25570449
TI  - Development of a system for the automatic detection of air embolism using a
      precordial Doppler.
AB  - Venous air embolism (VAE) is the air bubble accumulation in the right side of the
      heart. Changes in Doppler heart sound (DHS) are characteristic of VAE, and the
      anesthesiologist has to pay attention to this event continuously, which may not
      always be possible. This work aims to study different features of the heart sound
      through a precordial Doppler, that may provide useful information on VAE
      episodes. A clinical protocol was designed, and DHS was collected at baseline and
      following infusions of saline with 4 distinct volumes (1ml, 5ml, 8ml and 10ml),
      and two infusion rates (slow and fast), given by central and peripheric
      catheters. Signal was pre-processed, the envelope of each signal was extracted,
      and five features were implemented and evaluated: frequency corresponding to 95%
      of Welch periodogram power (f95), frequency corresponding to 50% of Welch
      periodogram power (f50), frequency corresponding to maximum power spectral
      density (fm), entropy (E), and frequency corresponding to maximum energy of a
      wavelet transform (freqwav). Relation between extracted features and saline
      infusions were studied and compared to baseline values. A Graphical User
      Interface (GUI) with a database of Doppler heart sounds and annotations was also
      developed. Although features present a high variability between patients, E
      presents a better performance showing an increase in response to saline
      injections (in 75% injections), followed by f95 (62%), fm (56.3%), freqwav
      (37.5%) and f50 (0%). 

PMID- 25570450
TI  - Online tracking of the lower body joint angles using IMUs for gait
      rehabilitation.
AB  - An important field in physiotherapy is the rehabilitation of gait. A continuous
      assessment and progress tracking of a patient's ability to walk is of clinical
      interest. Unfortunately the tools available to the therapists are very time
      consuming and subjective. Non-intrusive, small, wearable, wireless sensors can be
      worn by the patients and provide inertial measurements to estimate the pose of
      the lower body during walking. For this purpose, we propose two different
      kinematic models of the human lower body. We use an Extended Kalman Filter to
      estimate the joint angles and show that a variety of sensors, such as
      accelerometers, gyroscopes, and motion capture markers, can be used and fused
      together to aid the joint angle estimate. The algorithm is validated on gait data
      collected from healthy participants. 

PMID- 25570451
TI  - Correlation between muscular and nerve signals responsible for hand grasping in
      non-human primates.
AB  - Neuroprosthetic devices that interface with the nervous system to restore
      functional motor activity offer a viable alternative to nerve regeneration,
      especially in proximal nerve injuries like brachial plexus injuries where muscle
      atrophy may set in before nerve re-innervation occurs. Prior studies have used
      control signals from muscle or cortical activity. However, nerve signals are
      preferred in many cases since they permit more natural and precise control when
      compared to muscle activity, and can be accessed with much lower risk than
      cortical activity. Identification of nerve signals that control the appropriate
      muscles is essential for the development of such a 'bionic link'. Here we examine
      the correlation between muscle and nerve signals responsible for hand grasping in
      the M. fascicularis. Simultaneous recordings were performed using a 4-channel
      thin-film longitudinal intra-fascicular electrode (tf-LIFE) and 9 bipolar
      endomysial muscle electrodes while the animal performed grasping movements. We
      were able to identify a high degree of correlation (r > 0.6) between nerve
      signals from the median nerve and movement-dependent muscle activity from the
      flexor muscles of the forearm, with a delay that corresponded to 25 m/s nerve
      conduction velocity. The phase of the flexion could be identified using a wavelet
      approximation of the ENG. This result confirms this approach for a future
      neuroprosthetic device for the treatment of peripheral nerve injuries.

PMID- 25570452
TI  - Physiological responses to error amplification in a robotic reaching adaptation
      task.
AB  - Analysis of physiological responses provides an objective measure of a person's
      affective state and has been proposed as a way to evaluate motivation and
      engagement of therapy clients during robot-assisted therapy regimens. This paper
      presents the analysis of three physiological responses to different levels of
      error amplification in a robotic reaching task to understand the feasibility of
      using physiological signals in order to modify therapy exercises to achieve
      higher participant attentiveness. In a pilot study with 22 healthy participants,
      we analyzed skin conductance, skin temperature, and respiration signals, with two
      main goals: 1) to compare physiological parameters between baseline (rest) and
      error-amplified reaching motion periods; and 2) to compare physiological
      parameters between reaching motion periods with different levels of error
      amplification. Results show that features extracted from skin conductance and
      respiration signals show significant differences between different error
      amplification levels. Features extracted from the skin temperature signal are not
      as reliable as measures of skin conductance and respiration, however they can
      provide supplementary information. 

PMID- 25570453
TI  - Cell categories and K-nearest neighbor algorithm based decoding of primary motor
      cortical activity during reach-to-grasp task.
AB  - Neural decoding is a procedure to acquire intended movement information from
      neural activity and generate movement commands to control external devices such
      as intelligent prostheses. In this study, monkey Astra was trained to accomplish
      a 3-D reach-to-grasp task, and we recorded neural signals from its primary motor
      cortex (M1) during the task. The task-related cells were divided into four
      classes based on their correlation with two movement parameters: movement
      direction and orientation. We adopted the simple k-nearest neighbor (KNN)
      algorithm as the classifier, and chose cells from appropriate cell classes for
      movement parameter decoding. Cell classification was shown improving decoding
      accuracy with relatively less cells, even during movement planning stage (CRT).
      High decoding accuracy before movement actually performed is of great
      significance for intelligent prostheses control, and provides evidence that M1 is
      more than accepting ready-made movement commands but also participating in
      movement planning. We also found that population of task-related cells in M1 had
      a preference for specific direction and orientation, and this preference was more
      significant when it came to population of direction-related cells and orientation
      related cells. 

PMID- 25570454
TI  - Ultrasound signal quality parameterization for image-free evaluation of arterial
      stiffness.
AB  - We are in process of developing an image-free, single element ultrasound system
      for automated evaluation of arterial stiffness, we call it ARTSENS. The lack of a
      guiding image for arterial visualization necessitates intelligent analysis of
      ultrasound radio frequency (RF) echo signals to obtain reliable measurements. In
      this paper, we propose a novel algorithm to parameterize the echo signal received
      from the common carotid artery (CCA) to improve accuracy and reliability of
      arterial stiffness measurement. The echo signal quality is parameterized using
      features such as sharpness of arterial wall and energy ratio. A signal quality
      score is calculated by integrating the results from each feature. This score is
      used to triage the set of available echo signals recorded from each subject and
      select the best signal for computation of stiffness values. The performance of
      signal quality algorithm is tested using a database of carotid artery echo
      signals recorded from 28 human volunteers. It was observed that both the accuracy
      and reliability of the stiffness measurements were improved after triaging using
      the signal quality parameterization algorithm. 

PMID- 25570455
TI  - Upper limb functional assessment of children with cerebral palsy using a sorting
      box.
AB  - We investigated the use of a sorting box to obtain a quantitative assessment of
      upper limb motor function in children with cerebral palsy. In our study, children
      with and without cerebral palsy placed and removed geometrical objects of a
      sorting-box while their wrist position was monitored by a camera-based, motion
      tracking system. We analyzed three different smoothness metrics (logarithmic
      dimensionless jerk, spectral arc-length and number of peaks) together with time
      to task completion. Our results suggest that smoothness metrics are an effective
      tool to distinguish between impaired and non-impaired subjects, as well as to
      quantify differences between the affected and less-affected sides in children
      with hemiparetic cerebral palsy. 

PMID- 25570456
TI  - Identification of intestinal pacemaker frequency through time-frequency ridge
      analysis of surface EEnG.
AB  - The non-invasive monitoring of the frequency of intestinal pacemaker activity
      (slow wave, SW) has an important diagnostic value. However the presence of noise,
      physiological interferences and spurious peaks of the spectral estimators can
      yield to misidentification of SW frequency when using conventional dominant
      frequency detection method. In this paper, two methods of ridge extraction from
      the time-frequency distribution of human surface electroenterogram (EEnG) are
      proposed for the identification and tracking of SW frequency in 13 recording
      sessions of 120 minutes in 13 healthy volunteers. The minimum average distance
      method, that includes of information of previous and subsequent windows of
      analysis, yields the best results in terms of providing ridges that are longer,
      with less interruptions and with more stable frequency values which better suit
      the ubiquity and rhythmicity characteristics of the intestinal SW. This technique
      permits to reduce misinterpretations of intestinal SW frequency which can be of
      great importance in diagnostic applications of EEnG. 

PMID- 25570458
TI  - Comparative reliability analysis of publicly available software packages for
      automatic intracranial volume estimation.
AB  - Intracranial volume is an important measure in brain research often used as a
      correction factor in inter subject studies. The current study investigates the
      resulting outcome in terms of the type of software used for automatically
      estimating ICV measure. Five groups of 70 subjects are considered, including
      adult controls (AC) (n=11), adult with dementia (AD) (n=11), pediatric controls
      (PC) (n=18) and two groups of pediatric epilepsy subjects (PE1.5 and PE3) (n=30)
      using 1.5 T and 3T scanners, respectively. Reference measurements were calculated
      for each subject by manually tracing intracranial cavity without sub-sampling.
      Four publicly available software packages (AFNI, Freesurfer, FSL, and SPM) were
      examined in their ability to automatically estimate ICV across the five groups.
      Linear regression analyses suggest that reference measurement discrepancy could
      be explained best by SPM [R(2)= 0.67;p <; 0.01] for the AC group, Freesurfer
      [R(2) = 0.46; p = 0.02] for the AD group, AFNI [R(2)=0.97;p<; 0.01] for the PC
      group and FSL [R(2) = 0.6; p = 0.1] for the PE1.5 and [R(2) = 0.6; p <; 0.01] for
      PE3 groups. The study demonstrates that the choice of the automated software for
      ICV estimation is dependent on the population under consideration and whether the
      software used is atlas-based or not. 

PMID- 25570457
TI  - Basic characteristics of implantable flexible pressure sensor for wireless
      readout using MRI.
AB  - Measuring the local pressure in blood vessels is valuable in the postoperative
      monitoring of aneurysms. However, implanting a conventional pressure sensor
      equipped with power and signal cables causes difficulties during the operative
      procedure and carries a risk of infection after the implantation. In this study,
      we developed a wireless, implantable, and flexible pressure sensor. A magnetic
      resonance imaging (MRI) system reads out the sensor output. The proposed wireless
      sensor is based on an LC resonant circuit with a spiral coil and a pressure
      sensitive capacitor. The pressure-dependence of the capacitance affects the
      magnetic field produced by the spiral coil, changing the magnetization of the
      nearby sample that can be observed as a signal variation by MRI. We fabricated a
      prototype sensor using a capacitor with a silicone elastomer as the dielectric
      and a spiral coil made of gold. The maximum change in the capacitance was 8%
      under an external pressure of 20 kPa. A change in the thickness of the dielectric
      elastomer caused the capacitance to change, resulting in a signal variation
      detectable by MRI. 

PMID- 25570459
TI  - Functional validation of an implantable medical dosing device by MRI at 3T.
AB  - Sustained release of a small molecule from a prototype implantable drug delivery
      device was monitored via MRI in an ex vivo tissue phantom over a period of two
      days. T1 mapping was used as a method to quantify analyte concentration.
      Continuous, controlled release was observed. The MRI methodology was thus found
      to be appropriate for device validation and quality assurance/control. 

PMID- 25570460
TI  - Fast detection & modelling of the real osteoarthritic holes in the human knee
      with contour interpolated radial basis functions.
AB  - In this article, we propose a novel method for the fast 3D reconstruction of real
      osteoarthritic (OA) holes in a human femoral cartilage. Initially, semi-automated
      Region-Based Segmentation (region-growing) and Bounding Box techniques are used
      to extract femoral cartilage slices from MRI scans of the knee. OA holes were
      detected and filled automatically by our contour interpolation/RBF (CI-RBF)
      method and 3D models of both the femoral cartilage and OA holes were
      reconstructed separately. The method was then applied to a single human knee and
      results proved it fast, reliable and accurate for reconstructing a 3D model of
      the femoral cartilage from MRI images with an extremely low root mean square
      error of 1.67% in the estimated volume of the automatically filled to the
      manually filled femoral cartilage slices. As per authors' knowledge this is the
      first time real OA hole has automatically been identified and filled. 

PMID- 25570461
TI  - Effects of densely sampled dipole field on quantitative susceptibility mapping.
AB  - We present a method of resolving a fine structure in a magnetic susceptibility
      map, which cannot be distinguished by the conventional method, by using a densely
      sampled dipole field and by expanding a magnetic field perturbation map. We
      investigate effects of a sampling density of the dipole field on the spatial
      resolution and on obtained susceptibility values. When the sampling density is
      increased, a shape of an otherwise undistinguishable fine structure recovers
      gradually in an obtained susceptibility map. Furthermore, a peak susceptibility
      value of the fine structure is slowly getting closer to the correct values. 

PMID- 25570462
TI  - Kidney stone imaging with 3D ultra-short echo time (UTE) magnetic resonance
      imaging. A phantom study.
AB  - Computed tomography (CT) is the current gold standard for imaging kidney stones,
      albeit at the cost of radiation exposure. Conventional magnetic resonance imaging
      (MRI) sequences are insensitive to detecting the stones because of their
      appearance as a signal void. With the development of 2D ultra-short echo-time
      (UTE) MRI sequences, it becomes possible to image kidney stones in vitro. In this
      work, we optimize and implement a modified 3D UTE MRI sequence for imaging kidney
      stones embedded in agarose phantoms mimicking the kidney tissue and in urine
      phantoms at 3.0T. The proposed technique is capable of imaging the stones with
      high spatial resolution in a short scan time. 

PMID- 25570463
TI  - Ultra-high field birdcage coils: a comparison study at 14.1T.
AB  - An essential feature of magnetic resonance (MR) probes for magnetic resonance
      imaging and spectroscopy is the ability to generate uniform B(1)(+) excitation in
      a volume of interest. When the magnetic field strength is increased, leading to
      an increase in resonance frequency, the constraints on the MR probes size, the
      sample size and the associated radiation losses caused by conductor elements are
      higher. In this study we simulate, test and construct two birdcage coils for
      imaging rodents operated at 14.1 T. Bench experiments and imaging tests show that
      at 14.1 T dielectric resonance effect is the dominant factor accounting for
      B(1)(+) field inhomogeneity but remained achievable for imaging rodent brains.

PMID- 25570464
TI  - In vivo assessment of nervous fiber distribution in the intervertebral disc.
AB  - This present study aims to assess in vivo the nervous fibers distribution in the
      intervertebral disc using diffusion tensor imaging technique. Five healthy
      subjects participated into the data acquisition. Fiber extraction and tracking
      algorithms were used. The number of fibers in L4/5 disc ranges from 314 to 679
      and the mean fiber length L4/5 in disc ranges from 8.22 +/- 2.36 mm to 11.24 +/-
      5.17 mm. This study showed the feasibility of using diffusion tensor imaging
      technique to detect and assess the nervous fibers in the intervertebral discs.
      This could be of great clinical interest for the study of the correlations
      between these useful characteristics with pain levels on the low back pain
      patients. 

PMID- 25570465
TI  - A high throughput and efficient visualization method for diffusion tensor imaging
      of human brain white matter employing diffusion-map space.
AB  - Diffusion tensor imaging (DTI) possesses high dimension and complex structure, so
      that detecting available pattern information and its analysis based on
      conventional linear statistics and classification methods become inefficient. In
      order to facilitate classification, segmentation, compression or visualization of
      the data, dimension reduction is far-reaching. There have been many approaches
      proposed for this purpose, which mostly rely on complex low dimensional manifold
      embedding of the high-dimensional space. Dimension reduction is commonly
      applicable through linear algorithms, such as principal component analysis and
      multi-dimensional scaling; however, they are not able to deal with complex and
      high dimensional data. In this light, nonlinear algorithms with the capability to
      preserve the distance of high dimensional data have been developed. The purpose
      of this paper is to propose a new method for meaningful visualization of brain
      white matter using diffusion tensor data to map the 6-dimensional tensor to a
      three dimensional space employing Markov random walk and diffusion distance
      algorithms, leading to a new distance-preserving map for the DTI data with lower
      dimension and higher throughput information. 

PMID- 25570466
TI  - Optimized methodology for neonatal diffusion tensor imaging processing and study
      specific template construction.
AB  - Diffusion tensor imaging (DTI) has been widely used to study cerebral white
      matter microstructure in vivo. There is a plethora of open source tools available
      to perform pre-processing, analysis and template or atlas construction, however
      very few have been optimized for use with neonatal DTI data. Here we present a
      fully automated modular pipeline optimized for neonatal DTI data and the
      construction of study-specific tensor templates. We compare our methodology to an
      existing one. It is anticipated that the construction of population or study
      specific templates will facilitate better group comparisons of neonatal
      populations both in health and disease. 

PMID- 25570467
TI  - Interactive segmentation of white-matter fibers using a multi-subject atlas.
AB  - We present a fast algorithm for automatic segmentation of white matter fibers
      from tractography datasets based on a multi-subject bundle atlas. We describe a
      sequential version of the algorithm that runs on a desktop computer CPU, as well
      as a highly parallel version that uses a Graphics Processing Unit (GPU) as an
      accelerator. Our sequential implementation runs 270 times faster than a
      C++/Python implementation of a previous algorithm based on the same segmentation
      method, and 21 times faster than a highly optimized C version of the same
      previous algorithm. Our parallelized implementation exploits the multiple
      computation units and memory hierarchy of the GPU to further speed up the
      algorithm by a factor of 30 with respect to our sequential code. As a result, the
      time to segment a subject dataset of 800,000 fibers is reduced from more than 2.5
      hours in the Python/C++ code, to less than one second in the GPU version. 

PMID- 25570468
TI  - A preliminary study of DTI Fingerprinting on stroke analysis.
AB  - DTI (Diffusion Tensor Imaging) is a well-known MRI (Magnetic Resonance Imaging)
      technique which provides useful structural information about human brain.
      However, the quantitative measurement to physiological variation of subtypes of
      ischemic stroke is not available. An automatically quantitative method for DTI
      analysis will enhance the DTI application in clinics. In this study, we proposed
      a DTI Fingerprinting technology to quantitatively analyze white matter tissue,
      which was applied in stroke classification. The TBSS (Tract Based Spatial
      Statistics) method was employed to generate mask automatically. To evaluate the
      clustering performance of the automatic method, lesion ROI (Region of Interest)
      is manually drawn on the DWI images as a reference. The results from the DTI
      Fingerprinting were compared with those obtained from the reference ROIs. It
      indicates that the DTI Fingerprinting could identify different states of ischemic
      stroke and has promising potential to provide a more comprehensive measure of the
      DTI data. Further development should be carried out to improve DTI Fingerprinting
      technology in clinics. 

PMID- 25570469
TI  - Computer-aided detection of brain metastases using a three-dimensional template
      based matching algorithm.
AB  - The purpose of this work was to develop an algorithm for detecting brain
      metastases in magnetic resonance imaging (MRI), emphasizing the reduction of
      false positives. Firstly, three-dimensional templates were cross-correlated with
      the brain volume. Afterwards, each lesion candidate was segmented in the three
      orthogonal views as a previous step to remove elongated structures such as blood
      vessels. In a database containing 19 patients and 62 brain metastases, detection
      algorithm showed a sensitivity of 93.55%. After applying the method for false
      positive reduction, encouraging results were obtained: false positive rate per
      slice decreased from 0.64 to 0.15 and only one metastasis was removed, leading to
      a sensitivity of 91.94%. 

PMID- 25570470
TI  - The causal interaction within attention networks and emotion network: a fMRI
      study.
AB  - fMRI studies have suggested that there are two different attention networks: the
      dorsal attention network (DAN) and the ventral attention network (VAN). The
      emotion network has also been discovered by some researches. The dorsal attention
      network controls goal-oriented top-down deployment of attention; the ventral
      attention network controls stimulus-driven bottom-up deployment of attention; the
      emotion network will feed back the stimulus especially fearful expressions from
      the environment. The interaction within these networks has been noticed but few
      studies have been carried out. The purpose of this study is to explore the
      interaction within these networks. The regions of interest were acquired by using
      the GLM analysis after which the granger causality among these ROIs was
      calculated. Connections among ROIs were considered as causal when their
      respective granger causality value is greater than the mean value of all granger
      causalities. According to the results, there is interaction within the three
      networks, which suggested that the ventral attention network may distract the
      dorsal attention network and that the emotion network may influence both
      attention networks. 

PMID- 25570471
TI  - Classification of phosphorus magnetic resonance spectroscopic imaging of brain
      tumors using support vector machine and logistic regression at 3T.
AB  - This study aims classification of phosphorus magnetic resonance spectroscopic
      imaging ((31)P-MRSI) data of human brain tumors using machine-learning
      algorithms. The metabolite peak intensities and ratios were estimated for brain
      tumor and healthy (31)P MR spectra acquired at 3T. The spectra were classified
      based on metabolite characteristics using logistic regression and support vector
      machine. This study showed that machine learning could be successfully applied
      for classification of (31)P-MR spectra of brain tumors. Future studies will
      measure the performance of classification algorithms for (31)P-MRSI of brain
      tumors in a larger patient cohort. 

PMID- 25570472
TI  - On the characterization of single-event related brain activity from functional
      Magnetic Resonance Imaging (fMRI) measurements.
AB  - We propose an efficient numerical technique for calibrating the mathematical
      model that describes the single-event related brain response when fMRI
      measurements are given. This method employs a regularized Newton technique in
      conjunction with a Kalman filtering procedure. We have applied this method to
      estimate the biophysiological parameters of the Balloon model that describes the
      hemodynamic brain responses. Illustrative results obtained with both synthetic
      and real fMRI measurements are presented. 

PMID- 25570473
TI  - A variable splitting based algorithm for fast multi-coil blind compressed sensing
      MRI reconstruction.
AB  - Recent work on blind compressed sensing (BCS) has shown that exploiting sparsity
      in dictionaries that are learnt directly from the data at hand can outperform
      compressed sensing (CS) that uses fixed dictionaries. A challenge with BCS
      however is the large computational complexity during its optimization, which
      limits its practical use in several MRI applications. In this paper, we propose a
      novel optimization algorithm that utilize variable splitting strategies to
      significantly improve the convergence speed of the BCS optimization. The
      splitting allows us to efficiently decouple the sparse coefficient, and
      dictionary update steps from the data fidelity term, resulting in subproblems
      that take closed form analytical solutions, which otherwise require slower
      iterative conjugate gradient algorithms. Through experiments on multi coil
      parametric MRI data, we demonstrate the superior performance of BCS over
      conventional CS schemes, while achieving convergence speed up factors of over 10
      fold over the previously proposed implementation of the BCS algorithm. 

PMID- 25570474
TI  - Accelerated pharmacokinetic map determination for dynamic contrast enhanced MRI
      using frequency-domain based Tofts model.
AB  - Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) is widely used in
      the diagnosis of cancer and is also a promising tool for monitoring tumor
      response to treatment. The Tofts model has become a standard for the analysis of
      DCE-MRI. The process of curve fitting employed in the Tofts equation to obtain
      the pharmacokinetic (PK) parameters is time-consuming for high resolution scans.
      Current work demonstrates a frequency-domain approach applied to the standard
      Tofts equation to speed-up the process of curve-fitting in order to obtain the
      pharmacokinetic parameters. The results obtained show that using the frequency
      domain approach, the process of curve fitting is computationally more efficient
      compared to the time-domain approach. 

PMID- 25570475
TI  - Highly accelerated dynamic contrast-enhanced MRI with temporal constrained
      reconstruction.
AB  - For DCE MRI applications, the images of adjacent time frames are often similar,
      especially when motion is minimal, in which case temporal TV is a reasonable
      regularization term. Temporal constraint reconstruction (TCR) has been developed
      to reconstruct dynamic images from undersampled k-t space data based on such
      prior information. However, the convergence speed of the algorithm highly depends
      on the initialization method. In this study, we study initialization using a
      composite high resolution image based on a jigsaw sampling pattern during pre
      contrast frames. The proposed initialization method converges much faster than a
      conventional initialization method using low resolution images, especially at
      high reduction factors. In vivo breast imaging experiments were carried out to
      evaluate the performance of the proposed method. Experiments show the new
      initialization method allows TCR to achieve a high reduction factor up to 40
      without compromising much of the spatial or temporal resolution. The
      reconstruction errors are much lower than those using the low resolution
      initialization when the same number of measurements is used. 

PMID- 25570476
TI  - Accelerating the reconstruction of magnetic resonance imaging by three
      dimensional dual-dictionary learning using CUDA.
AB  - An effective way to improve the data acquisition speed of magnetic resonance
      imaging (MRI) is using under-sampled k-space data, and dictionary learning method
      can be used to maintain the reconstruction quality. Three-dimensional dictionary
      trains the atoms in dictionary in the form of blocks, which can utilize the
      spatial correlation among slices. Dual-dictionary learning method includes a low
      resolution dictionary and a high-resolution dictionary, for sparse coding and
      image updating respectively. However, the amount of data is huge for three
      dimensional reconstruction, especially when the number of slices is large. Thus,
      the procedure is time-consuming. In this paper, we first utilize the NVIDIA
      Corporation's compute unified device architecture (CUDA) programming model to
      design the parallel algorithms on graphics processing unit (GPU) to accelerate
      the reconstruction procedure. The main optimizations operate in the dictionary
      learning algorithm and the image updating part, such as the orthogonal matching
      pursuit (OMP) algorithm and the k-singular value decomposition (K-SVD) algorithm.
      Then we develop another version of CUDA code with algorithmic optimization.
      Experimental results show that more than 324 times of speedup is achieved
      compared with the CPU-only codes when the number of MRI slices is 24. 

PMID- 25570477
TI  - User-guided compressed sensing for magnetic resonance angiography.
AB  - Compressed sensing (CS) magnetic resonance imaging (MRI) enables the
      reconstruction of MRI images with fewer samples in k-space. One requirement is
      that the acquired image has a sparse representation in a known transform domain.
      MR angiograms are already sparse in the image domain. They can be further
      sparsified through finite-differences. Therefore, it is a natural application for
      CS-MRI. However, low-contrast vessels are likely to disappear at high
      undersampling ratios, since the commonly used L(1) reconstruction tends to
      underestimate the magnitude of the transformed sparse coefficients. These
      vessels, however, are likely to be clinically important for medical diagnosis. To
      avoid the fading of low-contrast vessels, we propose a user-guided CS MRI that is
      able to mitigate the reduction of vessel contrast within a region of interest
      (ROI). Simulations show that these low-contrast vessels can be well maintained
      via our method which results in higher local quality compared to conventional CS.

PMID- 25570478
TI  - Magnetic resonance image enhancement by reducing receptors' effective size and
      enabling multiple channel acquisition.
AB  - Magnetic resonance imaging is empowered by parallel reading, which reduces
      acquisition time dramatically. The time saved by parallelization can be used to
      increase image quality or to enable specialized scanning protocols in clinical
      and research environments. In small animals, the sizing constraints render the
      use of multi-channeled approaches even more necessary, as they help to improve
      the typically low spatial resolution and lesser signal-to-noise ratio; however,
      the use of multiple channels also generates mutual induction (MI) effects that
      impairs imaging creation. Here, we created coils and used the shared capacitor
      technique to diminish first degree MI effects and pre-amplifiers to deal with
      higher order MI-related image deterioration. The constructed devices are tested
      by imaging phantoms that contain identical solutions; thus, creating the
      conditions for several statistical comparisons. We confirm that the shared
      capacitor strategy can recover the receptor capacity in compounded coils when
      working at the dimensions imposed by small animal imaging. Additionally, we
      demonstrate that the use of pre-amplifiers does not significantly reduce the
      quality of the images. Moreover, in light of our results, the two MI-avoiding
      techniques can be used together, therefore establishing the practical feasibility
      of flexible array coils populated with multiple loops for small animal imaging. 

PMID- 25570479
TI  - Efficient compressed sensing SENSE parallel MRI reconstruction with joint
      sparsity promotion and mutual incoherence enhancement.
AB  - Magnetic resonance imaging (MRI) is considered a key modality for the future as
      it offers several advantages, including the use of non-ionizing radiation and
      having no known side effects on the human body, and has recently begun to serve
      as a key component of multi-modal neuroimaging. However, two major intrinsic
      problems exist: slow acquisition and intrusive acoustic noise. Parallel MRI
      (pMRI) techniques accelerate acquisition by reducing the duration and coverage of
      conventional gradient encoding. The under-sampled k-space data is detected with
      several receiver coils surrounding the object, using distinct spatial encoding
      information for each coil element to reconstruct the image. However, this
      scanning remains slow compared to typical clinical imaging (e.g. X-ray CT).
      Compressed Sensing (CS), a sampling theory based on random sub-sampling, has
      potential to further reduce the sampling used in pMRI, accelerating acquisition
      further. In this work, we propose a new CS SENSE pMRI reconstruction model
      promoting joint sparsity across channels and enhancing mutual incoherence to
      improve reconstruction accuracy from limited k-space data. For fast image
      reconstruction and fair comparisons, all reconstructions are computed with split
      Bregman and variable splitting techniques. Numerical results show that, with the
      introduced methods, reconstruction performance can be crucially improved with
      limited amount of k-space data. 

PMID- 25570480
TI  - Application of Region of Interest Compressed Sensing to accelerate magnetic
      resonance angiography.
AB  - Magnetic Resonance Angiography (MRA) is a group of techniques based on Magnetic
      Resonance Imaging (MRI) to image blood vessels. Compressed Sensing (CS) is a
      mathematical framework to reconstruct MR images from sparse data to minimize the
      data acquisition time. Image sparsity is the key in CS to reconstruct MR images.
      CS technique allows reconstruction from significantly fewer k-space samples as
      compared to full k-space acquisition, which results in reduced MRI data
      acquisition time. The images resulting from MRA are sparse in native
      representation, hence yielding themselves well to CS. Recently our group has
      proposed a novel CS method called Region of Interest Compressed Sensing (ROICS)
      as a part of Region of Interest (ROI) weighted CS. This work aims at the
      implementation of ROICS for the first time on MRA data to reduce MR data
      acquisition time. It has been demonstrated qualitatively and quantitatively that
      ROICS outperforms CS at higher acceleration factors. ROICS technique has been
      applied to 3D angiograms of the brain data acquired at 1.5T. It helps to reduce
      the MRA data acquisition time and improves the visualization of arteries. ROICS
      technique has been applied on 4 brain angiogram data sets at different
      acceleration factors from 2* to 10*. Reconstructed images show ROICS technique
      performs better than conventional CS technique and is quantified by the
      comparative Signal to Noise Ratio (SNR) in the ROI. 

PMID- 25570481
TI  - Improved image reconstruction for subspace-based spectroscopic imaging using non
      quadratic regularization.
AB  - A new MR spectroscopic imaging method, called SPICE (SPectroscopic Imaging by
      exploiting spatiospectral CorrElation), has been recently proposed to enable high
      resolution metabolic imaging with good SNR. A key problem within the SPICE
      framework is image reconstruction from a very noisy and sparsely sampled dataset.
      This paper addresses this problem by integrating the low-rank model used in SPICE
      reconstruction with a non-quadratic regularization. An efficient primal-dual
      based algorithm is described to solve the associated optimization problem. The
      proposed method has been validated using both simulation and phantom studies and
      is expected to enhance the unprecedented capability of SPICE for high-resolution
      metabolic imaging. 

PMID- 25570482
TI  - On verification of splines based intraoperative reconstruction of cardiac
      anatomy: model research.
AB  - Three-dimensional (3D) endocardium visualization plays an extremely important
      role in localization and ablation of target areas and can improve the cure rate
      in computer-aided cardiac surgery. In this paper, we discuss how to reconstruct
      and update the corresponding endocardium surface model quickly and accurately
      based on the sparse point cloud that is collected dynamically on the left atrial
      intima. Firstly, we construct a specific mesh model, and then collect spatial
      points, and carried out the mesh grid approximation based on Thin Plate Splines
      (TPS) intra-operatively, finally, we obtained an approximate target shape after
      Taubin-based smooth. Experiments on four left atriums' (LA) CT Angiographies
      (CTA) demonstrated that the reconstructed surfaces can well fit to the target
      shape, the distance error of surface between the reconstructed and targets can
      meet clinical requirements, and the deformation time can also meet the need of
      real-time update. The results showed that our proposed method is robust, fast and
      flexible to implement. 

PMID- 25570483
TI  - Endoscopic stereo reconstruction: a comparative study.
AB  - Advances in robotic surgery especially in minimally-invasive surgery (MIS) has
      increased the need for translating computer-vision algorithms in endoscopic
      imagery to support surgical decisions. While methods for stereo reconstruction
      have been extensively investigated for man-made environments, such an extensive
      and detailed study on the pros and cons of stereo reconstruction for endoscopic
      images. In this paper, we extensively compare several state-of-the-art methods on
      both simulated as well as real endoscopic images over controlled in-lab and
      phantom models observed by a daVinci stereo endoscope. The advantages and
      disadvantages of each compared method over the major steps of a stereo
      reconstruction pipeline are discussed and supported by exhaustive experiments and
      discussions. 

PMID- 25570484
TI  - Registration based super-resolution reconstruction for lung 4D-CT.
AB  - Lung 4D-CT plays an important role in lung cancer radiotherapy for tumor
      localization and treatment planning. In lung 4D-CT data, the resolution in the
      slice direction is often much lower than the in-plane resolution. For multi-plane
      display, isotropic resolution is necessary, but the commonly used interpolation
      operation will blur the images. In this paper, we present a registration based
      method for super resolution enhancement of the 4D-CT multi-plane images. Our
      working premise is that the low-resolution images of different phases at the
      corresponding position can be regarded as input "frames" to reconstruct high
      resolution images. First, we employ the Demons registration algorithm to estimate
      the motion field between different "frames". Then, the projections onto convex
      sets (POCS) approach is employed to reconstruction high-resolution lung images.
      We show that our method can get clearer lung images and enhance image structure,
      compared with the cubic spline interpolation and back projection method. 

PMID- 25570485
TI  - Design of an intra-operative imaging system for the cochlear implant.
AB  - Research has shown that closer proximity of a cochlear implant electrode array to
      the inner modiolar wall can improve hearing performance in a recipient. It is
      understood that developing a real-time intra-operative imaging technique would
      bring the surgeon visual feedback that can correlate with tactile resistances
      during electrode insertion, reducing various risks of insertion traumas, while
      guiding the electrode for optimal placement. This paper presents the design of a
      3-dimensional magnetic imaging system which provides a means for real-time
      imaging by reconstructing uniform segments of the electrode array's contours. In
      addition, the theoretical error of this reconstruction method is evaluated to
      select an optimal number of sensors within the electrode design. The theoretical
      error of the reconstruction method is evaluated for 7 to 22 inductive sensors
      within the electrode design. For 16 or more sensors, the error is improves to
      less than 0.5%. A working prototype was confirmed on a 10:1 scale with orthogonal
      Helmholtz coils at 85-115 kHz.

PMID- 25570486
TI  - An improved YEF-DCT based compression algorithm for video capsule endoscopy.
AB  - Video capsule endoscopy is a non-invasive technique to receive images of
      intestine for medical diagnostics. The main design challenges of endoscopy
      capsule are accruing and transmitting acceptable quality images by utilizing as
      less hardware and battery power as possible. In order to save wireless
      transmission power and bandwidth, an efficient image compression algorithm needs
      to be implemented inside the endoscopy electronic capsule. In this paper, an
      integer discrete-cosine-transform (DCT) based algorithm is presented that works
      on a low-complexity color-space specially designed for wireless capsule endoscopy
      application. First of all, thousands of human endoscopic images and video frames
      have been analyzed to identify special intestinal features present in those
      frames. Then a color space, referred as YEF, is used. The YEF converter is
      lossless and takes only a few adders and shift operation to implement. A low-cost
      quantization scheme with variable chroma sub-sampling options is also implemented
      to achieve higher compression. Comparing with the existing works, the proposed
      transform coding based compressor performs strongly with an average compression
      ratio of 85% and a high image quality index, peak-signal-to-noise ratio (PSNR) of
      52 dB. 

PMID- 25570487
TI  - A novel optimized parallelization strategy to accelerate microwave tomography for
      breast cancer screening.
AB  - Microwave tomography has been proven to successfully reconstruct the dielectric
      profile of a human breast when used in breast imaging applications, thereby
      providing an alternative to other imaging modalities. However, the method suffers
      from high computational requirements which restrict its use in practical imaging
      systems. This paper presents a novel parallelization strategy to accelerate
      microwave tomography for reconstruction of the dielectric properties of the human
      breast. A Time Domain algorithm using this parallelization strategy has been
      validated and benchmarked against an optimized sequential implementation on a
      conventional high-end desktop Central Processing Unit (CPU), and a comparison of
      throughput is presented in this paper. The gain in computational throughput is
      shown to be significantly higher compared with the sequential implementation,
      ranging from a factor of 26 to 58, on imaging grid sizes of up to 25 cm square at
      1 mm resolution.

PMID- 25570488
TI  - Human eyeball model reconstruction and quantitative analysis.
AB  - Determining shape of the eyeball is important to diagnose eyeball disease like
      myopia. In this paper, we present an automatic approach to precisely reconstruct
      three dimensional geometric shape of eyeball from MR Images. The model
      development pipeline involved image segmentation, registration, B-Spline surface
      fitting and subdivision surface fitting, neither of which required manual
      interaction. From the high resolution resultant models, geometric characteristics
      of the eyeball can be accurately quantified and analyzed. In addition to the
      eight metrics commonly used by existing studies, we proposed two novel metrics,
      Gaussian Curvature Analysis and Sphere Distance Deviation, to quantify the cornea
      shape and the whole eyeball surface respectively. The experiment results showed
      that the reconstructed eyeball models accurately represent the complex morphology
      of the eye. The ten metrics parameterize the eyeball among different subjects,
      which can potentially be used for eye disease diagnosis. 

PMID- 25570489
TI  - Effects of genetic variation on the dynamics of neurodegeneration in Alzheimer's
      disease.
AB  - Although many genetic markers are identified as being associated with Alzheimer's
      disease (AD), not much is known about their association with the structural
      changes that happen as the disease progresses. In this study, we investigate the
      genetic etiology of neurodegeneration in AD by associating genetic markers with
      atrophy profiles obtained using patient data from the Alzheimer's Disease
      Neuroimaging Initiative (ADNI) cohort. The atrophy profiles were quantified using
      a linear least-squares regression model over the span of patient enrollment, and
      used as imaging features throughout the analysis. A subset of the imaging
      features were selected for genetic association based on their ability to
      discriminate between healthy individuals and AD patients in a Support Vector
      Machines (SVM) classifier. Each imaging feature was associated with single
      nucleotide polymorphisms (SNPs) using a linear model that included age and
      cognitive impairment scores as covariates to correct for normal disease
      progression. After false discovery rate correction, we observed 53 significant
      associations between SNPs and our imaging features, including associations of
      ventricular enlargement with SNPs on estrogen receptor 1 (ESR1) and sortilin
      related VPS10 domain containing receptor 1 (SORCS1), hippocampal atrophy with
      SNPs on ESR1, and cerebral atrophy with SNPs on transferrin (TF) and amyloid beta
      precursor protein (APP). This study provides important insights into genetic
      predictors of specific types of neurodegeneration that could potentially be used
      to improve the efficacy of treatment strategies for the disease and allow the
      development of personalized treatment plans based on each patient's unique
      genetic profile. 

PMID- 25570490
TI  - Altered small-world anatomical networks in Apolipoprotein-E4 (ApoE4) carriers
      using MRI.
AB  - Apolipoprotein E (ApoE) gene and primarily its allele e4 have been identified as
      a risk factor for Alzheimer's disease (AD). The prevalence of the gene in 25-30%
      in the population makes it essential to estimate its role in neuroregulation and
      its impact on distributed brain networks. In this study, we provide computational
      neuroanatomy based interpretation of large-scale and small-world cortical
      networks in cognitive normal (CN) subjects with differing Apolipoprotein-E4
      (ApoE4) gene expression. We estimated large-scale anatomical networks from
      cortical thickness measurements derived from magnetic resonance imaging in 147 CN
      subjects explored in relation to ApoE4 genotype (e4+ carriers (n=41) versus e4-
      non-carriers (n=106)). Brain networks were constructed by thresholding cortical
      thickness correlation matrices of 68 bilateral regions of the brain analyzed
      using well-established graph theoretical approaches. Compared to ApoE4 non
      carriers, carriers showed increased interregional correlation coefficients in
      regions like precentral, superior frontal and inferior temporal regions.
      Interestingly most of the altered connections were intra-hemispheric limited
      primarily to the right hemisphere. Furthermore, ApoE4 carriers demonstrated
      abnormal small-world architecture in the cortical networks with increased
      clustering coefficient and path lengths as compared to non-carrier, suggesting a
      less optimal topological organization. Additionally non-carriers demonstrated
      higher betweenness in regions such as middle temporal, para-hippocampal gyrus,
      posterior cingulate and insula of the default mode network (DMN), also seen in
      subjects with AD and mild cognitive impairment (MCI). The results suggest that
      the complex morphological cortical connectivity patterns are altered in ApoE4
      carriers as compared to non-carriers, providing evidence for disruption of
      integrity in large-scale anatomical brain networks. 

PMID- 25570491
TI  - Screening for pre-diabetes using support vector machine model.
AB  - The global prevalence of diabetes is rapidly increasing. Studies support
      screening and interventions for pre-diabetes, which results in serious
      complications and diabetes. This study aimed at developing an intelligence-based
      screening model for pre-diabetes that could assist with decreasing the prevalence
      of diabetes through early identification and subsequent interventions. Data from
      the Korean National Health and Nutrition Examination Survey (KNHANES) were used,
      excluding subjects with diabetes. The KNHANES 2010 data (n = 4,685) were used for
      training and internal validation, while data from KNHANES 2011 (n = 4,566) were
      used for external validation. We developed a model to screen for pre-diabetes
      using support vector machine (SVM), and performed a systematic evaluation of the
      SVM model using internal and external validation. We compared the performance of
      the SVM model with that of a screening score model based on logistic regression
      analysis for pre-diabetes that had been developed previously. Backward
      elimination logistic regression resulted in associations between pre-diabetes and
      age, sex, waist circumference, body mass index, alcohol intake, family history of
      diabetes, and hypertension. The areas under the curves (AUCs) for the SVM model
      in the internal and external datasets were 0.761 and 0.731, respectively, while
      the AUCs for the screening score model were 0.734 and 0.712, respectively. The
      SVM model developed in this study performed better than the screening score model
      that had been developed previously and may be more effective for pre-diabetes
      screening. 

PMID- 25570492
TI  - Item response analysis of Alzheimer's Disease Assessment Scale.
AB  - Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) suffers from
      low sensitivity in detecting changes in Alzheimer's disease progression in
      clinical trials of disease-modifying treatments. A comprehensive psychometric
      analysis of the items in ADAS-cog assessment can help in identifying and
      improving the insensitive items. Item response theory provides a suitable
      framework for investigating the ADAS-cog items; however, it requires prior
      information on the underlying latent construct for reliable analysis. In this
      study, we perform an exploratory item response analysis to investigate the latent
      construct underlying the relationships between the ADAS-cog item responses. The
      results indicate that the underlying latent construct of ADAS-cog is
      multidimensional in nature with the latent factors measuring cognitive declines
      in several domains (such as memory, praxis, and language domains). 

PMID- 25570493
TI  - Development of a diffusion-based mathematical model for predicting chemotherapy
      effects.
AB  - Mathematical modeling of drug transport can complement current experimental and
      clinical investigations to understand drug resistance mechanisms, which
      eventually will help to develop patient-specific chemotherapy treatments. In this
      paper, we present a general time- and space-dependent mathematical model based on
      diffusion theory for predicting chemotherapy outcome. This model has two
      important parameters: the blood volume fraction and radius of blood vessels
      divided by drug diffusion penetration length. Model analysis finds that a larger
      ratio of the radius of blood vessel to diffusion penetration length resulted in
      to a larger fraction of tumor killed, thereby leading to a better treatment
      outcome. Clinical translation of the model can help quantify and predict the
      optimal dosage size and frequency of chemotherapy for individual patients. 

PMID- 25570494
TI  - A multi-tissue segmentation of the human head for detailed computational models.
AB  - This paper describes the creation of an anatomically detailed high resolution
      model of the human head based on the Visible Human Female data from the National
      Library of Medicine archives. Automatic and semi-automatic segmentation
      algorithms were applied over the 3 image volumes - CT, MRI and anatomical cryo
      sections of the cadaver - to label a total of 23 tissues. The results were
      combined to create a labeled volume of the head with voxel dimensions of
      0.33*0.33*0.33 mm. The individual label matrices and their corresponding surface
      meshes are made available to be used freely. The detailed blood vessel network
      and ocular tissues will be of interest in computational modelling and simulation
      studies.

PMID- 25570495
TI  - A smart pressure-sensitive insole that reminds you to walk correctly: an orthotic
      less treatment for over pronation.
AB  - We equipped an insole with a force sensor that can detect in real time when a
      foot over pronates. When such behavior is detected, we warn the user so they can
      correct their posture by using their own muscles. The effectiveness of this novel
      way to correct over pronation posture is evaluated over a two-week period. The
      use of vibrotactile feedback reduces over pronation by 30% to 50% during the
      first week. The natural benefits of the proposed method vs. use of passive
      orthotics are also presented. 

PMID- 25570496
TI  - Minimum jerk swing control allows variable cadence in powered transfemoral
      prostheses.
AB  - We present a novel swing phase controller for powered transfemoral prostheses
      based on minimum jerk theory. The proposed controller allows physiologically
      appropriate swing movement at any walking speed, regardless of the stance
      controller action. Preliminary validation in a transfemoral amputee subject
      demonstrates that the proposed controller provides physiological swing timing,
      without speed-or patient-specific tuning. 

PMID- 25570497
TI  - Development of multichannel soft tactile sensors having fingerprint structure.
AB  - It is possible to accurately recognize the shape of an object or to grip it by
      setting soft tactile sensors on a robot's hands. We studied a multichannel soft
      tactile sensor as an artificial hand and evaluated the pressure's response
      performance from several directions and the slipping and sliding responses. The
      tactile sensor consisted of multiple pneumatic sensors and a soft cap with a
      fingerprint structure that was made of silicone gum and was separated from
      multiple spaces. Evaluation tests showed that the multiple soft tactile sensors
      estimate both an object's contact force and its contact location. Our tactile
      sensor also measured the object's roughness by the slide on surface texture. 

PMID- 25570498
TI  - Designing and testing a hybrid lightweight shoulder prosthesis.
AB  - Lightweight prostheses are preferred in terms of usability in daily living.
      However, this is not a property easy to realize, especially for shoulder
      prostheses. High portability, multiple degrees of freedom (DOFs) with an
      appropriate ROM (range of motion), sufficient end-effector power, and suitable
      viscoelasticity for the safe use in daily living, usually result in a heavy
      weight. In this paper, a hybrid shoulder prosthesis that combined servo motors
      and pneumatic elastic actuators, with a weight distribution scheme, was designed
      to meet the requirements. The prosthetic system was preliminarily tested by
      comparing its ADL (activities of daily living) motion data with that of an intact
      arm. The experiment results showed that the shoulder prosthesis could reproduce
      the motion of an intact arm, thus demonstrate its usability in daily living. 

PMID- 25570500
TI  - Assessment of gait direction changes during straight-ahead walking in healthy
      elderly and Huntington disease patients using a shank worn MIMU.
AB  - The aim of this study was to propose and comparatively evaluate four methods for
      assessing stride-by-stride changes of direction of progression, during straight
      walking using measurements of a magnetic and inertial unit placed above the
      malleolus. The four methods were evaluated by comparing their estimate of the
      gait changes of direction of progression with that obtained from an instrumented
      gait mat used as a gold standard. The methods were applied to the data obtained
      from the gait of both healthy subjects and patients with Huntington Disease, the
      latter characterized by a jerky swing phase. The results showed that the errors
      associated to the best estimates of the gait direction changes were about 10% of
      its range of variability for the healthy subjects and increased to about 30% for
      the patients, both walking at comfortable speed when the range of variability is
      the largest. Additional testing on gait at various radius of curvature should be
      carried out to fully validate the MIMU-based estimates. 

PMID- 25570499
TI  - Contributions of knee swing initiation and ankle plantar flexion to the walking
      mechanics of amputees using a powered prosthesis.
AB  - Recently developed powered prostheses are capable of producing near-physiological
      joint torque at the knee and/or ankle joints. Based on previous studies of
      biological joint impedance and the mechanics of able-bodied gait, an impedance
      based controller has been developed for a powered knee and ankle prosthesis that
      integrates knee swing initiation and powered plantar flexion in late stance with
      increasing ankle stiffness throughout stance. In this study, five prosthesis
      configuration conditions were tested to investigate the individual contributions
      of each sub-strategy to the overall walking mechanics of four unilateral
      transfemoral amputees as they completed a clinical 10-m walk test using a powered
      knee and ankle prosthesis. The baseline condition featured constant ankle
      stiffness and no swing initiation or powered plantar flexion. The four remaining
      conditions featured knee swing initiation alone (SI) or in combination with
      powered plantar flexion (SI+PF), increasing ankle stiffness (SI+IK), or both
      (SI+PF+IK). Self-selected walking speed did not significantly change between
      conditions, although subjects tended to walk the slowest in the baseline
      condition compared to conditions with swing initiation. The addition of powered
      plantar flexion resulted in significantly higher ankle power generation in late
      stance irrespective of ankle stiffness. The inclusion of swing initiation
      resulted in a significantly more flexed knee at toe off and a significantly
      higher average extensor knee torque following toe off. Identifying individual
      contributions of intrinsic control strategies to prosthesis biomechanics could
      help inform the refinement of impedance-based prosthesis controllers and simplify
      future designs of prostheses and lower-limb assistive devices alike. 

PMID- 25570501
TI  - Motion based markerless gait analysis using standard events of gait and ensemble
      Kalman filtering.
AB  - We present a novel approach to gait analysis using ensemble Kalman filtering
      which permits markerless determination of segmental movement. We use image flow
      analysis to reliably compute temporal and kinematic measures including the
      translational velocity of the torso and rotational velocities of the lower leg
      segments. Detecting the instances where velocity changes direction also
      determines the standard events of a gait cycle (double-support, toe-off, mid
      swing and heel-strike). In order to determine the kinematics of lower limbs, we
      model the synergies between the lower limb motions (thigh-shank, shank-foot) by
      building a nonlinear dynamical system using CMUs 3D motion capture database. This
      information is fed into the ensemble Kalman Filter framework to estimate the
      unobserved limb (upper leg and foot) motion from the measured lower leg
      rotational velocity. Our approach does not require calibrated cameras or special
      markers to capture movement. We have tested our method on different gait
      sequences collected from the sagttal plane and presented the estimated kinematics
      overlaid on the original image frames. We have also validated our approach by
      manually labeling the videos and comparing our results against them.

PMID- 25570502
TI  - Hierarchical task ordering for time reduction on KINARM assessment protocol.
AB  - Advances in robotic technologies offer objective, highly reliable tools for
      assessment of brain function following stroke. KINARM is an exoskeleton device
      that uses a number of behavioral tasks to objectively quantify sensorimotor,
      proprioceptive and cognitive brain function. As more tasks are developed to more
      broadly assess different aspects of behavior using the robot, different
      strategies are required to reduce the overall assessment time. The present study
      investigates how non-linear hierarchical ordering theory can be applied to
      determine the ordering on a set of four tasks on the KINARM exoskeleton robot.
      Evaluation is based on task discretization, which determines whether an
      individual passes or fails a certain task on the robot. Results of the study
      suggest an ordering which determines the results of success or failure on a
      sensorimotor task for the unaffected arm of stroke survivors based on the
      assessment results of a ball drop object-hit task with 97% confidence. This can
      be used to reduce the assessment time by over eight minutes for a subgroup of
      stroke survivors compared to the current KINARM assessment protocol. 

PMID- 25570503
TI  - Quantitative evaluation of unrestrained human gait on change in walking velocity.
AB  - In human gait motion analysis, which is one useful method for efficient physical
      rehabilitation to define various quantitative evaluation indices, ground reaction
      force, joint angle and joint loads are measured during gait. To obtain these data
      as unrestrained gait measurement, a novel gait motion analysis system using
      mobile force plates and attitude sensors has been developed. On the other hand, a
      human maintains a high correlation among the motion of all joints during gait.
      The analysis of the correlation in the recorded joint motion extracts a few
      simultaneously activating segmental coordination patterns, and the structure of
      the intersegmental coordination is attracting attention to an expected
      relationship with a control strategy. However, when the evaluation method using
      singular value decomposition has been applied to joint angles of the lower limb
      as representative kinematic parameters, joint moments related to the rotational
      motion of the joints have not yet been considered. In this paper, joint moments
      as kinetic parameters applied on the lower limb during gait of a normal subject
      and a trans-femoral amputee are analyzed under change in walking velocity by the
      wearable gait motion analysis system, and the effectiveness for quantitatively
      evaluate the rotational motion pattern in the joints of the lower limb by using
      joint moments is validated. 

PMID- 25570504
TI  - Evaluation of upper extremity movement characteristics during standardized
      pediatric functional assessment with a Kinect(r)-based markerless motion analysis
      system.
AB  - A recently developed and evaluated upper extremity (UE) markerless motion
      analysis system based on the Microsoft(r) Kinect(r) has potential for improving
      functional assessment of patients with hemiplegic cerebral palsy. 12 typically
      developing adolescents ages 12-17 were evaluated using both the Kinect-based
      system and the Shriners Hospitals for Children Upper Extremity Evaluation
      (SHUEE), a validated measure of UE motion. The study established population means
      of UE kinematic parameters for each activity. Statistical correlation analysis
      was used to identify key kinematic metrics used to develop automatic scoring
      algorithms. The Kinect motion analysis platform is technically sound and can be
      applied to standardized task-based UE evaluation while providing enhanced
      sensitivity in clinical analysis and automation through scoring algorithms. 

PMID- 25570505
TI  - Linear and nonlinear subspace analysis of hand movements during grasping.
AB  - This study investigated nonlinear patterns of coordination, or synergies,
      underlying whole-hand grasping kinematics. Prior research has shed considerable
      light on roles played by such coordinated degrees-of-freedom (DOF), illuminating
      how motor control is facilitated by structural and functional specializations in
      the brain, peripheral nervous system, and musculoskeletal system. However,
      existing analyses suppose that the patterns of coordination can be captured by
      means of linear analyses, as linear combinations of nominally independent DOF. In
      contrast, hand kinematics is itself highly nonlinear in nature. To address this
      discrepancy, we sought to to determine whether nonlinear synergies might serve to
      more accurately and efficiently explain human grasping kinematics than is
      possible with linear analyses. We analyzed motion capture data acquired from the
      hands of individuals as they grasped an array of common objects, using four of
      the most widely used linear and nonlinear dimensionality reduction algorithms. We
      compared the results using a recently developed algorithm-agnostic quality
      measure, which enabled us to assess the quality of the dimensional reductions
      that resulted by assessing the extent to which local neighborhood information in
      the data was preserved. Although qualitative inspection of this data suggested
      that nonlinear correlations between kinematic variables were present, we found
      that linear modeling, in the form of Principle Components Analysis, could perform
      better than any of the nonlinear techniques we applied. 

PMID- 25570506
TI  - Development of MRI-powered modular robotic system.
AB  - This study proposes a novel robotic system controlled by the magnetic forces
      generated from Magnetic Resonance Imaging (MRI) scanner. In the proposed system,
      ferromagnetic particles are used to actuate the device, while all other parts are
      made of nonmagnetic materials. The possible range of motion for the particles is
      investigated by using the common sequence which is usually available for MR
      imaging. We then designed a mechanism that extends the observed pendular motion
      to rotational movement. By using the designed mechanism, we realized a MRI
      powered multiaxial robotic system. The potential application of this system
      covers the automation for under MRI inspections such as esthesiometry and needle
      biopsy. In this paper, we described the fundamental principle of the MRI-powered
      robotic system and also report on the performance evaluation of the robotic
      system. 

PMID- 25570507
TI  - Towards a multi-level neural architecture that unifies self-intended and imitated
      arm reaching performance.
AB  - Dexterous arm reaching movements are a critical feature that allow human
      interactions with tools, the environment, and socially with others. Thus the
      development of a neural architecture providing unified mechanisms for actual,
      mental, observed and imitated actions could enhance robot performance, enhance
      human-robot social interactions, and inform specific human brain processes. Here
      we present a model, including a fronto-parietal network that implements
      sensorimotor transformations (inverse kinematics, workspace visuo-spatial
      rotations), for self-intended and imitation performance. Our findings revealed
      that this neural model can perform accurate and robust 3D actual/mental arm
      reaching while reproducing human-like kinematics. Also, using visuo-spatial
      remapping, the neural model can imitate arm reaching independently of a
      demonstrator-imitator viewpoint. This work is a first step towards providing the
      basis of a future neural architecture for combining cognitive and sensorimotor
      processing levels that will allow for multi-level mental simulation when
      executing actual, mental, observed, and imitated actions for dexterous arm
      movements. 

PMID- 25570508
TI  - Open-source, low-cost, compliant, modular, underactuated fingers: towards
      affordable prostheses for partial hand amputations.
AB  - In this paper we present a series of design directions for the development of
      affordable, compliant, modular, underactuated robot fingers, that can be used as
      prostheses by amputees that suffer from various partial hand amputations (index
      to pinky fingers are considered). Our design is based on parametric models that
      have been derived from hand anthropometry studies. Various interfaces have been
      considered in order to control the prosthesis, depending on the type and level of
      amputation. More precisely: 1) An Electromyography (EMG) based interface is used
      to control the robot fingers employing the EMG signals of the human forearm
      muscles 2) A flex sensors based interface is used to record the motion of the
      intact finger/fingers and predict the motion of the prosthesis implementing a
      synergistic behavior in an efficient manner, 3) A body powered interface is used
      for those that want to achieve even lower cost, with robust intuitive operation.
      Following the proposed design directions, an amputee will be able to replicate
      our fingers and develop personalized, affordable, light-weight but yet efficient
      prostheses. 

PMID- 25570509
TI  - Promise of using surface EMG signals to volitionally control ankle joint position
      for powered transtibial prostheses.
AB  - Improving the intuitiveness of the interaction between human and machine is an
      important issue for powered lower-limb prosthesis control. In this research, we
      aimed to evaluate the potential of using surface electromyography (EMG) signals
      measured from transtibial amputees' residual muscles to directly control the
      position of prosthetic ankle. In this research, one transtibial amputee subject
      and five able-bodied subjects were recruited. They were asked to control a
      virtual ankle to reach different target positions. The amputee subject finished
      these tasks in an average time of 1.29 seconds for different target positions
      with the residual limb, which was comparable with that using the amputee's sound
      limb and those with able-bodied subjects' dominant legs. Due to human's strong
      adaptability, the amputee subject was able to adapt to the control model trained
      one day before or trained in a posture which was different from that during
      performing control tasks. These results validate the promise of using surface EMG
      signals to volitionally control powered transtibial prostheses. 

PMID- 25570510
TI  - Using wavelet analysis to reveal the muscle functional recovery following nerve
      reinnervation in a rat model.
AB  - Targeted muscle reinnervation (TMR) technique has been successful in many
      amputees for providing sufficient electromyography (EMG) signal to control
      advanced prosthetics. However, it seems to lack further understanding of the
      recovery progress of muscle functions after targeted muscle reinneveration
      surgery. In this study, a rat TMR model was developed to investigate
      intramuscular EMG activity changes after reinnervation. Using the discrete
      wavelet decomposition and average rectified algorithm, the recorded EMG showed a
      gradual improvement in the reinnervated muscle within four weeks. Future work
      will be performed to further assess the efficiency of reinnveration therapy after
      the surgery. 

PMID- 25570511
TI  - Motor cortical decoding performance depends on controlled system order.
AB  - Recent advances in intracortical brain-machine interfaces (BMIs) for position
      control have leveraged state estimators to decode intended movements from
      cortical activity. We revisit the underlying assumptions behind the use of Kalman
      filters in this context, focusing on the fact that identified cortical coding
      models capture closed-loop task dynamics. We show that closed-loop models can be
      partitioned, exposing feedback policies of the brain which are separate from
      interface and task dynamics. Changing task dynamics may cause the brain to change
      its control policy, and consequently the closed-loop dynamics. This may degrade
      performance of decoders upon switching from manual tasks to velocity-controlled
      BMI-mediated tasks. We provide experimental results showing that for the same
      manual cursor task, changing system order affects neural coding of movement. In
      one experimental condition force determines position directly, and in the other
      force determines cursor velocity. From this we draw an analogy to subjects
      transitioning from manual reaching tasks to velocity-controlled BMI tasks. We
      conclude with suggested principles for improving BMI decoder performance,
      including matching the controlled system order between manual and brain control,
      and identifying the brain's controller dynamics rather than complete closed-loop
      dynamics.

PMID- 25570512
TI  - A semi-active hybrid neuroprosthesis for restoring lower limb function in
      paraplegics.
AB  - Through the application of functional electrical stimulation (FES) individuals
      with paraplegia can regain lost walking function. However, due to the rapid onset
      of muscle fatigue, the walking duration obtained with an FES-based
      neuroprosthesis is often relatively short. The rapid muscle fatigue can be
      compensated for by using a hybrid system that uses both FES and an active
      orthosis. In this paper, we demonstrate the initial testing of a semi-active
      hybrid walking neuroprosthesis. The semi-active hybrid orthosis (SEAHO) supports
      a user during the stance phase and standing while the electric motors attached to
      the hip section of the orthosis are used to generate hip flexion/extension. FES
      in SEAHO is mainly used to actuate knee flexion/extension and plantar flexion of
      the foot. SEAHO is controlled by a finite state machine that uses a recently
      developed nonlinear controller for position tracking control of the hip motors
      and cues from the hip angle to actuate FES and other components. 

PMID- 25570513
TI  - Intelligent algorithm tuning PID method of function electrical stimulation using
      knee joint angle.
AB  - Functional electrical stimulation (FES) could restore motor functions for
      individuals with spinal cord injury (SCI). By applying electric current pulses,
      FES system could produce muscle contractions, generate joint torques, and thus,
      achieve joint movements automatically. Since the muscle system is highly
      nonlinear and time-varying, feedback control is quite necessary for precision
      control of the preset action. In the present study, we applied two methods
      (Proportional Integral Derivative (PID) controller based on Back Propagation (BP)
      neural network and that based on Genetic Algorithm (GA)), to control the knee
      joint angle for the FES system, while the traditional Ziegler-Nichols method was
      used in the control group for comparison. They were tested using a muscle model
      of the quadriceps. The results showed that intelligent algorithm tuning PID
      controller displayed superior performance than classic Ziegler-Nichols method
      with constant parameters. More particularly, PID controller tuned by BP neural
      network was superior on controlling precision to make the feedback signal track
      the desired trajectory whose error was less than 1.2 degrees +/-0.16 degrees ,
      while GA-PID controller, seeking the optimal parameters from multipoint
      simultaneity, resulted in shortened delay in the response. Both strategies showed
      promise in application of intelligent algorithm tuning PID methods in FES system.

PMID- 25570514
TI  - Using thin-film piezoelectret to detect tactile and slip signals for restoring
      sensation of prosthetic hands.
AB  - Most of the currently available prosthetic hands do not have a proper sensation
      of touching and slipping. Thus it is not easy for arm amputees to grasp objects
      properly only with an assistance of visual feedback. In this pilot work, a sensor
      based on thin-film piezoelectret was used to detect the possible tactile and slip
      information of a prosthetic hand. The piezoelectret sensor is flexible and is
      able to be bended, and therefore it could be properly mounted on the surface of
      prosthetic finger. Our preliminary results demonstrated that both the tactile and
      slip information could be acquired with the same sensor unit. For a grasp without
      slippage, the tactile signal was usually a single large peak, whereas the slip
      signal was a series of vibrations in a small range. Thus these two types of
      signals could be easily separated based on their different characteristics. This
      study suggested that by using thin-film piezoelectret sensor, a primary control
      with involuntary feedback might be achieved for the present prosthetic hands.
      More studies would be required on the detailed signal processing and control
      strategy for the restoration of sensation function in prosthetic hands. 

PMID- 25570515
TI  - Effects of non-training movements on the performance of motion classification in
      electromyography pattern recognition.
AB  - In electromyography pattern-recognition-based control of a multifunctional
      prosthesis, it would be inevitable for the users to unintentionally perform some
      classes of movements that are excluded from the training motion classes of a
      classifier, which might decay the performance of a trained classifier. It remains
      unknown how these untrained movements, designated as non-target movements (NTMs)
      in the study, would affect the performance of a trained classifier in the control
      of multifunctional prostheses. The goal of the current study was to evaluate the
      effects of NTMs on the performance of movement classification. Five classes of
      target movements (TMs) and four classes of NTMs were considered in this pilot
      study. A classifier based on a linear discriminant analysis (LDA) was trained
      with the electromyography (EMG) signals from the five TMs and the effects of the
      four NTMs were examined by feeding the EMG signals of the four NTMs to the
      trained classifier. Our results showed that these NTMs were classified into one
      or more classes of the TMs, which would cause the unexpected movements of
      prostheses. A method to reduce the effects of NTMs has been proposed in the study
      and our results showed that the averaged classification accuracies of the
      corrected classifiers were above 99% for the healthy subjects. 

PMID- 25570516
TI  - Magnetic stimulation of mammalian peripheral nerves in vivo: an alternative to
      functional electrical stimulation.
AB  - Functional electrical stimulation is the current gold standard for stimulating
      neuronal interfaces for functional neuromuscular and cortical applications, but
      it is not without its drawbacks. One such fault is the need to have direct
      electrical contact with the nerve tissue, and any side effects this causes.
      Functional magnetic stimulation, which works though electromagnetic induction,
      does not require electrical contact and may be a viable alternative to functional
      electrical stimulation. We are investigating the capabilities of magnetic
      stimulation with centimeter scale (< 2.5 cm) coils in feline and rodent sciatic
      nerves in vivo. We have shown that magnetic stimulation can consistently produce
      the same levels of neuromuscular activation as electrical stimulation.
      Additionally, the position of the coil relative to the nerve influences
      neuromuscular activation, suggesting the possibility of selective muscle
      activation.

PMID- 25570518
TI  - Preliminary design of an energy storing orthosis for providing gait to people
      with spinal cord injury.
AB  - A new design is proposed for an energy storing orthosis (ESO) that restores
      walking to people with spinal cord injury by combining functional electrical
      stimulation of the quadriceps muscle with a mechanical brace that uses elastic
      elements to store and transfer energy between hip and knee joints. The new ESO is
      a variation of a previous design and uses constant force springs for energy
      storage. Based on the detailed design and on dynamic simulations, the concept has
      demonstrated preliminary technical feasibility. 

PMID- 25570517
TI  - Towards better understanding and reducing the effect of limb position on
      myoelectric upper-limb prostheses.
AB  - Myoelectric control of prosthetic devices tend to rely on classification schemes
      of extracted features of EMG data. Those features however, may be sensitive to
      arm position resulting in decreased performance in real-world applications. The
      effect of varying limb position in a pattern recognition system have been
      illustrated by documenting the change in classification accuracy as the user
      achieves particular limb configurations. We continue to investigate this limb
      position effect by observing its impact on classification accuracy as well as
      through an analysis of how each extracted feature of the raw EMG varies in each
      position. Finally, LDA classification schemes are applied both to demonstrate the
      effect varying limb position has on classification accuracy and to increase
      classification accuracy without the use of additional hardware or sensors such as
      accelerometers as has been done in the past. It is shown that high classification
      accuracy can be achieved by (1) training an LDA classifier with data from many
      positions, as well as (2) by utilizing an extra position LDA classifier which can
      weigh the grasp classifiers appropriately. The classification accuracies achieved
      by these methods approached that of a model relying on a perfect knowledge of arm
      position. 

PMID- 25570519
TI  - Wayfinding with simulated prosthetic vision: performance comparison with regular
      and structure-enhanced renderings.
AB  - In this study, we used a simulation of upcoming low-resolution visual
      neuroprostheses to evaluate the benefit of embedded computer vision techniques in
      a wayfinding task. We showed that augmenting the classical phosphene rendering
      with the basic structure of the environment - displaying the ground plane with a
      different level of brightness - increased both wayfinding performance and
      cognitive mapping. In spite of the low resolution of current and upcoming visual
      implants, the improvement of these cognitive functions may already be possible
      with embedded artificial vision algorithms. 

PMID- 25570522
TI  - Towards photorealistic and immersive virtual-reality environments for simulated
      prosthetic vision: integrating recent breakthroughs in consumer hardware and
      software.
AB  - Simulated prosthetic vision (SPV) in normally sighted subjects is an established
      way of investigating the prospective efficacy of visual prosthesis designs in
      visually guided tasks such as mobility. To perform meaningful SPV mobility
      studies in computer-based environments, a credible representation of both the
      virtual scene to navigate and the experienced artificial vision has to be
      established. It is therefore prudent to make optimal use of existing hardware and
      software solutions when establishing a testing framework. The authors aimed at
      improving the realism and immersion of SPV by integrating state-of-the-art yet
      low-cost consumer technology. The feasibility of body motion tracking to control
      movement in photo-realistic virtual environments was evaluated in a pilot study.
      Five subjects were recruited and performed an obstacle avoidance and wayfinding
      task using either keyboard and mouse, gamepad or Kinect motion tracking. Walking
      speed and collisions were analyzed as basic measures for task performance. Kinect
      motion tracking resulted in lower performance as compared to classical input
      methods, yet results were more uniform across vision conditions. The chosen
      framework was successfully applied in a basic virtual task and is suited to
      realistically simulate real-world scenes under SPV in mobility research.
      Classical input peripherals remain a feasible and effective way of controlling
      the virtual movement. Motion tracking, despite its limitations and early state of
      implementation, is intuitive and can eliminate between-subject differences due to
      familiarity to established input methods. 

PMID- 25570520
TI  - Assessing vibrotactile feedback strategies by controlling a cursor with unstable
      dynamics.
AB  - Brain computer interface (BCI) control predominately uses visual feedback. Real
      arm movements, however, are controlled under a diversity of feedback mechanisms.
      The lack of additional BCI feedback modalities forces users to maintain visual
      contact while performing tasks. Such stringent requirements result in poor BCI
      control during tasks that inherently lack visual feedback, such as grasping, or
      when visual attention is diverted. Using a modified version of the Critical
      Tracking Task which we call the Critical Stability Task (CST), we tested the
      ability of 9 human subjects to control an unstable system using either free arm
      movements or pinch force. The subjects were provided either visual feedback,
      'proportional' vibrotactile feedback, or 'on-off' vibrotactile feedback about the
      state of the unstable system. We increased the difficulty of the control task by
      making the virtual system more unstable. We judged the effectiveness of a
      particular form of feedback as the maximal instability the system could reach
      before the subject lost control of it. We found three main results. First,
      subjects can use solely vibrotactile feedback to control an unstable system,
      although control was better using visual feedback. Second, 'proportional'
      vibrotactile feedback provided slightly better control than 'on-off' vibrotactile
      feedback. Third, there was large intra-subject variability in terms of the most
      effective input and feedback methods. This highlights the need to tailor the
      input and feedback methods to the subject when a high degree of control is
      desired. Our new task can provide a complement to traditional center-out
      paradigms to help boost the real-world relevance of BCI research in the lab.

PMID- 25570521
TI  - Biomimetic stimulation of rat retinal ganglion cells with the neurotransmitter
      glutamate.
AB  - Millions of people worldwide face partial or total vision loss due to inherited
      photoreceptor degenerative diseases, which currently have no cure. Retinal
      prostheses have been developed to restore vision by electrically stimulating
      surviving retinal neurons, but have low spatial resolution and nonselectively
      stimulate retinal ganglion cell (RGC) axons along with somata. We propose a
      biomimetic solution: using the neurotransmitter glutamate to chemically stimulate
      RGCs to avoid the disadvantages of electrical stimulation. Our results
      demonstrate that glutamate stimulation has a spatial resolution comparable to
      current-generation electrical prostheses, can stimulate RGC somata without
      stimulating axons, and can produce spatially differential responses in RGC
      subtypes. These results highlight the benefits of a neurotransmitter-based
      retinal prosthesis over current-generation electrical prostheses. 

PMID- 25570523
TI  - Electronically induced contrast enhancement in whisker S1 cortical response
      fields.
AB  - The ability of an organism to specifically attend to relevant sensory information
      during learning and subsequent performance of a task is highly dependent on the
      release of the neurotransmitter Acetylcholine (ACh). Electrophysiological studies
      have shown that pairing endogenous ACh with specific visual or auditory stimuli
      induces long lasting enhancements of subsequent cortical responses to the
      previously paired stimulus. In this study we present data suggesting that similar
      effects can be elicited in the rat whisker sensory system. Specifically, we show
      that pairing whisker deflection with electrical stimulation of the magnocellular
      basal nucleus (BN: a natural source of cortical ACh) causes an increase in the
      center-surround contrast of the treated whisker's cortical response field (CRF).
      Meanwhile, deflections of whiskers distant from the treated whisker show overall
      increased response magnitudes, but non-significant changes in contrast between
      principle vs. surround barrel responses. Control trials, in which BN stimulation
      was not paired with whisker deflection, showed similar lack of contrast
      enhancement. These results indicate that BN stimulation, paired with incoming
      whisker information, selectively increases the paired whisker's CRF center
      surround contrast, while unpaired BN stimulation causes a more general increases
      in S1 responsiveness, without contrast modulation. Enhanced control over whisker
      sensory pathway attentional mechanisms has the potential to facilitate a more
      effective transfer of desired information to the animal's neural processing
      circuitry, thereby allowing experimental evaluation of more complex behavior and
      cognition than was previously possible. 

PMID- 25570524
TI  - Towards closed-loop deep brain stimulation: decision tree-based essential tremor
      patient's state classifier and tremor reappearance predictor.
AB  - Deep Brain Stimulation (DBS) is a surgical procedure to treat some progressive
      neurological movement disorders, such as Essential Tremor (ET), in an advanced
      stage. Current FDA-approved DBS systems operate open-loop, i.e., their parameters
      are unchanged over time. This work develops a Decision Tree (DT) based algorithm
      that, by using non-invasively measured surface EMG and accelerometer signals as
      inputs during DBS-OFF periods, classifies the ET patient's state and then
      predicts when tremor is about to reappear, at which point DBS is turned ON again
      for a fixed amount of time. The proposed algorithm achieves an overall accuracy
      of 93.3% and sensitivity of 97.4%, along with 2.9% false alarm rate. Also, the
      ratio between predicted tremor delay and the actual detected tremor delay is
      about 0.93, indicating that tremor prediction is very close to the instant where
      tremor actually reappeared. 

PMID- 25570525
TI  - On modeling the neuronal activity in movement disorder patients by using the
      Ornstein Uhlenbeck process.
AB  - Mathematical models of the neuronal activity in the affected brain regions of
      Essential Tremor (ET) and Parkinson's Disease (PD) patients could shed light into
      the underlying pathophysiology of these diseases, which in turn could help
      develop personalized treatments including adaptive Deep Brain Stimulation (DBS).
      In this paper, we use an Ornstein Uhlenbeck Process (OUP) to model the neuronal
      spiking activity recorded from the brain of ET and PD patients during DBS
      stereotactic surgery. The parameters of the OUP are estimated based on Inter
      Spike Interval (ISI) measurements, i.e., the time interval between two
      consecutive neuronal firings, by means of the Fortet Integral Equation (FIE). The
      OUP model parameters identified with the FIE method (OUP-FIE) are then used to
      simulate the ISI distribution resulting from the OUP. Other widely used neuronal
      activity models, such as the Poisson Process (PP), the Brownian Motion (BM), and
      the OUP whose parameters are extracted by matching the first two moments of the
      ISI (OUP-MOM), are also considered. To quantify how close the simulated ISI
      distribution is to the measured ISI distribution, the Integral Square Error (ISE)
      criterion is adopted. Amongst all considered stochastic processes, the ISI
      distribution generated by the OUP-FIE method is shown to produce the least ISE.
      Finally, a directional Wilcoxon signed rank test is used to show statistically
      significant reduction in the ISE value obtained from the OUP-FIE compared to the
      other stochastic processes. 

PMID- 25570526
TI  - Research on brain induced effect by extremely low frequency pulsed magnetic
      stimulation.
AB  - In order to evaluate the influence of extremely low frequency pulsed magnetic
      fields (ELF PMF) on human brain, we conducted the magnetic stimulation
      experiments (1 Hz, 10 mT, 20 min), and analyzed the changes of spontaneous EEG
      activity from 10 subjects. Compared with sham exposure group, the EEG power of
      theta band (3.5-7.5 Hz) and lower-alpha band (7.5-10 Hz) from the stimulation
      group increased significantly after magnetic stimulation. By analyzing the
      latency period and amplitude of P300 in auditory oddball task, we found that the
      latency period extended and the amplitude decreased. We suggested that these
      results might be explained via event-related synchronization induced by magnetic
      stimulation. 

PMID- 25570527
TI  - A latent force model for describing electric propagation in deep brain
      stimulation: a simulation study.
AB  - Deep brain stimulation (DBS) is a neurosurgical method used to treat symptoms of
      movement disorders by implanting electrodes in deep brain areas. Often, the DBS
      modeling approaches found in the literature assume a quasi-static approximation,
      and discard any dynamic behavior. Nevertheless, in a real DBS system the stimulus
      corresponds to a wave that changes as a function of time. It is clear that DBS
      demands an approach that takes into account the time-varying behavior of the
      input stimulus. In this work, we present a novel latent force model for
      describing the dynamic electric propagation occurred during DBS. The performance
      of the proposed model was studied by simulations under different conditions. The
      results show that our approach is able to take into account the time variations
      of the source and the produced field. Moreover, by restricting our model it is
      possible to obtain solutions for electrostatic formulations, here experimental
      results were compared with the finite element method. Additionally, our approach
      allows a solution to the inverse problem, which is a valuable clinical
      application allowing the appropriate tuning of the DBS device by the expert
      physician. 

PMID- 25570528
TI  - Localization of subthalamic nucleus borders using macroelectrode local field
      potential recordings.
AB  - Deep brain stimulation of the subthalamic nucleus (STN) is a highly effective
      treatment for motor symptoms of Parkinson's disease. However, precise
      intraoperative localization of STN remains a procedural challenge. In the present
      study, local field potentials (LFPs) were recorded from DBS macroelectrodes
      during trajectory to STN, in six patients. The frequency-vs-depth map of LFP
      activity was extracted and further analyzed within different sub-bands, to
      investigate whether LFP activity can be used for STN border identification. STN
      borders identified by LFPs were compared to border predictions by the
      neurosurgeon, based on microelectrode-derived, single-unit recordings (MER-SUA).
      The results demonstrate difference between MER-SUA and macroelectrode LFP
      recording with respect to the dorsal STN border of -1.00 +/-0.84 mm and -0.42 +/
      1.07 mm in the beta and gamma frequency bands, respectively. For these sub-bands,
      RMS of these distances was found to be 1.26 mm and 1.06 mm, respectively.
      Analysis of other sub-bands did not allow for distinguishing the caudal border of
      STN. In conclusion, macroelectrode-derived LFP recordings may provide an
      alternative approach to MER-SUA, for localizing the target STN borders during DBS
      surgery. 

PMID- 25570529
TI  - Beamforming approaches for untethered, ultrasonic neural dust motes for cortical
      recording: a simulation study.
AB  - In this paper, we examine the use of beamforming techniques to interrogate a
      multitude of neural implants in a distributed, ultrasound-based intra-cortical
      recording platform known as Neural Dust. We propose a general framework to
      analyze system design tradeoffs in the ultrasonic beamformer that extracts neural
      signals from modulated ultrasound waves that are backscattered by free-floating
      neural dust (ND) motes. Simulations indicate that high-resolution linearly
      constrained minimum variance beamforming sufficiently suppresses interference
      from unselected ND motes and can be incorporated into the ND-based cortical
      recording system.

PMID- 25570530
TI  - Logistic-weighted regression improves decoding of finger flexion from
      electrocorticographic signals.
AB  - One of the most interesting applications of brain computer interfaces (BCIs) is
      movement prediction. With the development of invasive recording techniques and
      decoding algorithms in the past ten years, many single neuron-based and
      electrocorticography (ECoG)-based studies have been able to decode trajectories
      of limb movements. As the output variables are continuous in these studies, a
      regression model is commonly used. However, the decoding of limb movements is not
      a pure regression problem, because the trajectories can be apparently classified
      into a motion state and a resting state, which result in a binary property
      overlooked by previous studies. In this paper, we propose an algorithm called
      logistic-weighted regression to make use of the property, and apply the algorithm
      to a BCI system decoding flexion of human fingers from ECoG signals. Our results
      show that the application of logistic-weighted regression improves decoding
      performance compared to the application of linear regression or pace regression.
      The proposed algorithm is also immensely valuable in the other BCIs decoding
      continuous movements. 

PMID- 25570531
TI  - Short-wavelength near infrared stimulation of the inner ear hair cells.
AB  - To explore whether the short wavelength near infrared laser can stimulate the
      functional hair cells, pulsed laser with wavelength of 808-nm was used to
      stimulate guinea pigs cochlea. Compound action potential (CAP) and auditory
      brainstem responses (ABR) were recorded during the experiments. We successfully
      recorded photomechanical responses from normal hearing animals and demonstrated
      the responses were not induced by optical acoustic events. Furthermore, we
      studied the effect of different stimulation parameters on neural response. The
      results show that cochlear activation can be modulated with different optical
      parameters. 

PMID- 25570532
TI  - Real time algorithms for sharp wave ripple detection.
AB  - Neural activity during sharp wave ripples (SWR), short bursts of co-ordinated
      oscillatory activity in the CA1 region of the rodent hippocampus, is implicated
      in a variety of memory functions from consolidation to recall. Detection of these
      events in an algorithmic framework, has thus far relied on simple thresholding
      techniques with heuristically derived parameters. This study is an investigation
      into testing and improving the current methods for detection of SWR events in
      neural recordings. We propose and profile methods to reduce latency in ripple
      detection. Proposed algorithms are tested on simulated ripple data. The findings
      show that simple realtime algorithms can improve upon existing power thresholding
      methods and can detect ripple activity with latencies in the range of 10-20 ms. 

PMID- 25570533
TI  - Optimal EEG feature selection from average distance between events and non
      events.
AB  - Biosignal classification systems often have to deal with extraneous features,
      highly imbalanced datasets, and a low SNR. A robust feature selection/reduction
      method is a crucial step in this process. Sets of artificial data were generated
      to test a prototype EEG-based microsleep detection system, consisting of a
      combination of EEG and 2-s bursts of 15-Hz sinusoids of varied signal-to-noise
      ratios (SNRs) ranging from 16 to 0.03. The balance between events and non-events
      was varied between evenly balanced and highly imbalanced (e.g., events occurring
      only 2% of the time). Features were spectral estimates of various EEG bands
      (e.g., alpha band power) or ratios between them. A total of 34 features for each
      of the 16 channels yielded a total of 544 features. Five minutes of EEG from a
      total of eight subjects were used in the generation of the artificial data.
      Several feature reduction and classifier structures were investigated. Taking
      only a single feature corresponding to the maximum of average distance between
      events and non-events (ADEN) on unbalanced data yielded a phi correlation of 0.94
      on the mock data with an SNR of 0.3, compared with a phi coefficient of 0.00 for
      principal component analysis (PCA). ADEN consistently outperformed alternative
      system configurations, independent of the classifier utilized. While ADEN's high
      performance may be due to the nature of the artificial dataset, this simulation
      has demonstrated strong potential compared to other feature selection/reduction
      methods. 

PMID- 25570534
TI  - Fibre-selective discrimination of physiological ENG using velocity selective
      recording: report on pilot rat experiments.
AB  - This paper presents results from a pilot experiment in which the technique of
      velocity selective recording (VSR) was used to identify naturally occurring
      electroneurogram (ENG) signals within the intact nerve of a rat. Signals were
      acquired using a set of electrodes placed along the length of the nerve, formed
      from simple wire hooks. This basic form of recording has already been applied in
      vivo to the analysis of electrically excited compound action potentials (CAPs) in
      both pig and frog, however, this method has never before been used to identify
      naturally occurring neural signals. Results in this paper highlight challenges
      which must be overcome in order for the transition to be made from electrically
      evoked potentials to naturally occurring signals. 

PMID- 25570535
TI  - An integrated power, area and noise efficient AFE for large scale multichannel
      neural recording systems.
AB  - A wideband, low-power, low-noise and area-efficient analog front-end (AFE) for
      acquiring neural signals is described. The AFE builds upon existing architectures
      but uses block-wise optimization to achieve superior performance when used in a
      multichannel system with scalable channel count. The AFE is also the first of its
      kind to enable acquisition from extended neural bandwidths greater than 10 kHz.
      The AFE is designed in 65 nm CMOS technology and consumes 11.3 MUW of power while
      occupying 0.06 mm(2) per channel and delivering an NEF of 2.92. 

PMID- 25570536
TI  - Objective assessment of listening effort in the oscillatory EEG: comparison of
      different hearing aid configurations.
AB  - An objective estimate of listening effort could support the hearing aid fitting
      procedure. Most of the digital hearing aids have already hearing aid settings
      which are supposed to reduce the listening effort, but the effects of these
      settings on the individual's listening effort remain unclear. In this study, we
      propose an objective estimate of listening effort using electroencephalographic
      data. The new method is based on the phase distribution of the ongoing
      oscillatory EEG activity. We hypothesize that for a non-effortful listening
      environment the phase is rather uniformly distributed on the unit circle than for
      a demanding condition. To prove if the phase is uniformly distributed around the
      unit circle, the Rayleigh Test was applied to the phase of the EEG. This method
      was tested in 14 hearing impaired subjects (moderate hearing loss, 65.64 +/-7.93
      yrs, 7 female). The tested hearing aid settings were a directional microphone
      combined with a noise reduction algorithm in a medium and a strong setting, the
      noise reduction setting turned off as well as a setting using omnidirectional
      microphones. Noise embedded sentences (Oldenburg Sentence Test, OlSa) were used
      as test materials. The task of the subject was to repeat each sentence. The
      results indicate that the objective estimate of listening effort maps the
      subjectively rated effort and for a listening situation like the presented one,
      the strong setting of the directional microphone requires the smallest effort. 

PMID- 25570537
TI  - Unsupervised learning of electrocorticography motifs with binary descriptors of
      wavelet features and hierarchical clustering.
AB  - We describe a novel method for data mining spectro-spatiotemporal network motifs
      from electrocorticographic (ECoG) data. The method utilizes wavelet feature
      extraction from ECoG data, generation of compact binary vectors from these
      features, and binary vector hierarchical clustering. The potential utility of
      this method in the discovery of recurring neural patterns is demonstrated in an
      example showing clustering of ictal and post-ictal gamma activity patterns. The
      method allows for the efficient and scalable retrieval and clustering of neural
      motifs occurring in massive amounts of neural data, such as in prolonged EEG/ECoG
      recordings and in brain computer interfaces. 

PMID- 25570538
TI  - Comparative analysis of cognitive tasks for modeling mental workload with
      electroencephalogram.
AB  - Previous electroencephalogram (EEG) studies have shown that cognitive workload
      can be estimated by using several types of cognitive tasks. In this study, we
      attempted to characterize cognitive tasks that have been used to manipulate
      workload for generating classification models. We carried out a comparative
      analysis between two representative types of working memory tasks: the n-back
      task and the mental arithmetic task. Based on experiments with 7 healthy subjects
      using Emotiv EPOC, we compared the consistency, robustness, and efficiency of
      each task in determining cognitive workload in a short training session. The
      mental arithmetic task seems consistent and robust in manipulating clearly
      separable high and low levels of cognitive workload with less training. In
      addition, the mental arithmetic task shows consistency despite repeated usage
      over time and without notable task adaptation in users. The current study
      successfully quantifies the quality and efficiency of cognitive workload modeling
      depending on the type and configuration of training tasks. 

PMID- 25570539
TI  - A study of predicting movement intentions in various spatial reaching tasks from
      M1 neural activities.
AB  - Understanding how M1 neurons innervate flexible coordinated upper limb reaching
      and grasping is important for BMI systems that attempt to reproduce the same
      actions. In this paper, we presented a study for exploring M1 neuronal activities
      while a non-human primate subject was guided to finish different visual cued
      spatial reaching and grasping tasks. By applying various configurations of target
      objects in the experiment paradigm, we can make thorough investigations on how
      neural ensemble activities represented subjects' intentions in different task
      related time stages when target objects' properties, including shape, position,
      orientation, varied. Extracted neuron units were categorized according to their
      event related attributes. The prediction of subjects' movement intentions was
      completed with a support vector machine (SVM) based method and a simulated on
      line test was performed to illustrate the validation of the proposed method. The
      results showed that, by M1 neural ensemble spike train signals, correct
      prediction of subject's intentions can be generated in certain time intervals
      before the movements were actually executed. 

PMID- 25570540
TI  - A comparison of alerting strategies for hemorrhage identification during
      prehospital emergency transport.
AB  - Early and accurate identification of physiological abnormalities is one feature
      of intelligent decision support. The ideal analytic strategy for identifying
      pathological states would be highly sensitive and highly specific, with minimal
      latency. In the field of manufacturing, there are well-established analytic
      strategies for statistical process control, whereby aberrancies in a
      manufacturing process are detected by monitoring and analyzing the process
      output. These include simple thresholding, the sequential probability ratio test
      (SPRT), risk-adjusted SPRT, and the cumulative sum method. In this report, we
      applied these strategies to continuously monitored prehospital vital-sign data
      from trauma patients during their helicopter transport to level I trauma centers,
      seeking to determine whether one strategy would be superior. We found that
      different configurations of each alerting strategy yielded widely different
      performances in terms of sensitivity, specificity, and average time to alert.
      Yet, comparing the different investigational analytic strategies, we observed
      substantial overlap among their different configurations, without any one
      analytic strategy yielding distinctly superior performance. In conclusion,
      performance did not depend as much on the specific analytic strategy as much as
      the configuration of each strategy. This implies that any analytic strategy must
      be carefully configured to yield the optimal performance (i.e., the optimal
      balance between sensitivity, specificity, and latency) for a specific use case.
      Conversely, this also implies that an alerting strategy optimized for one use
      case (e.g., long prehospital transport times) may not necessarily yield
      performance data that are optimized for another clinical application (e.g., short
      prehospital transport times, intensive care units, etc.). 

PMID- 25570542
TI  - A platform for real-time acquisition and analysis of physiological data in
      hospital emergency departments.
AB  - An opportunity exists for automated clinical decision support, in which raw
      source data from a conventional physiological monitoring system are continuously
      streamed to an independent analysis platform. Such a system would enable a wider
      range of functionality than offered by the source monitoring system. Although
      vendor solutions for this purpose are emerging, we developed our own system in
      order to control the expense and to permit forensic analysis of the internal core
      functionality of the system. In this report, we describe a platform that can
      provide decision support for trauma patients in an Emergency Department (ED).
      System evaluation spanned 39 days, and included a total of 2200 patient session
      hrs of real-time monitoring. We highlight the technical issues that we
      confronted, including protection of the core monitoring network, the real-time
      communication of electronic medical data, and the reliability of the real-time
      analysis. Detailing these nuanced technical issues may be valuable to other
      software developers or for those interested in investing in a vendor solution for
      similar functionality. 

PMID- 25570541
TI  - Intelligent remote health monitoring using evident-based DSS for automated
      assistance.
AB  - The shift from common diagnosis practices to continuous monitoring based on body
      sensors has transformed healthcare from hospital-centric to patient-centric.
      Continuous monitoring generates huge and continuous amount of data revealing
      changing insights. Existing approaches to analyze streams of data in order to
      produce validated decisions relied mostly on static learning and analytics
      techniques. In this paper, we propose an incremental learning and adaptive
      analytics scheme relying on evident data and rule-based Decision Support System
      (DSS). The later continuously enriches its knowledge base with incremental
      learning information impacting the decision and proposing up-to-date
      recommendations. Some intelligent features augmented the monitoring scheme with
      data pre-processing and cleansing support, which helped empowering data analytics
      efficiency. Generated assistances are viewable to users on their mobile devices
      and to physician via a portal. We evaluate our incremental learning and analytics
      scheme using seven well-known learning techniques. The set of experimental
      scenarios of continuous heart rate and ECG monitoring demonstrated that the
      incremental learning combined with rule-based DSS afforded high classification
      accuracy, evidenced decision, and validated assistance. 

PMID- 25570543
TI  - Mobile DIORAMA-II: infrastructure less information collection system for mass
      casualty incidents.
AB  - In this paper we introduce DIORAMA-II system that provides real time information
      collection in mass casualty incidents. Using a mobile platform that includes
      active RFID tags and readers as well as Smartphones, the system can determine the
      location of victims and responders. The system provides user friendly multi
      dimensional user interfaces as well as collaboration tools between the responders
      and the incident commander. We conducted two simulated mass casualty incidents
      with 50 victims each and professional responders. DIORAMA-II significantly
      reduces the evacuation time by up to 43% when compared to paper based triage
      systems. All responders that participated in all trials were very satisfied. They
      felt in control of the incident and mentioned that the system significantly
      reduced their stress level during the incident. They all mentioned that they
      would use the system in an actual incident. 

PMID- 25570544
TI  - Smartphone application for classification of motor impairment severity in
      Parkinson's disease.
AB  - Advanced hardware components embedded in modern smartphones have the potential to
      serve as widely available medical diagnostic devices, particularly when used in
      conjunction with custom software and tested algorithms. The goal of the present
      pilot study was to develop a smartphone application that could quantify the
      severity of Parkinson's disease (PD) motor symptoms, and in particular,
      bradykinesia. We developed an iPhone application that collected kinematic data
      from a small cohort of PD patients during guided movement tasks and extracted
      quantitative features using signal processing techniques. These features were
      used in a classification model trained to differentiate between overall motor
      impairment of greater and lesser severity using standard clinical scores provided
      by a trained neurologist. Using a support vector machine classifier, a
      classification accuracy of 0.945 was achieved under 6-fold cross validation, and
      several features were shown to be highly discriminatory between more severe and
      less severe motor impairment by area under the receiver operating characteristic
      curve (AUC > 0.85). Accurate classification for discriminating between more
      severe and less severe bradykinesia was not achieved with these methods. We
      discuss future directions of this work and suggest that this platform is a first
      step toward development of a smartphone application that has the potential to
      provide clinicians with a method for monitoring patients between clinical
      appointments. 

PMID- 25570545
TI  - Comparison of real-time classification systems for arrhythmia detection on
      Android-based mobile devices.
AB  - The electrocardiogram (ECG) is a key diagnostic tool in heart disease and may
      serve to detect ischemia, arrhythmias, and other conditions. Automatic, low cost
      monitoring of the ECG signal could be used to provide instantaneous analysis in
      case of symptoms and may trigger the presentation to the emergency department.
      Currently, since mobile devices (smartphones, tablets) are an integral part of
      daily life, they could form an ideal basis for automatic and low cost monitoring
      solution of the ECG signal. In this work, we aim for a realtime classification
      system for arrhythmia detection that is able to run on Android-based mobile
      devices. Our analysis is based on 70% of the MIT-BIH Arrhythmia and on 70% of the
      MIT-BIH Supraventricular Arrhythmia databases. The remaining 30% are reserved for
      the final evaluation. We detected the R-peaks with a QRS detection algorithm and
      based on the detected R-peaks, we calculated 16 features (statistical, heartbeat,
      and template-based). With these features and four different feature subsets we
      trained 8 classifiers using the Embedded Classification Software Toolbox (ECST)
      and compared the computational costs for each classification decision and the
      memory demand for each classifier. We conclude that the C4.5 classifier is best
      for our two-class classification problem (distinction of normal and abnormal
      heartbeats) with an accuracy of 91.6%. This classifier still needs a detailed
      feature selection evaluation. Our next steps are implementing the C4.5 classifier
      for Android-based mobile devices and evaluating the final system using the
      remaining 30% of the two used databases. 

PMID- 25570546
TI  - Sensor-based activity recognition using extended belief rule-based inference
      methodology.
AB  - The recently developed extended belief rule-based inference methodology (RIMER+)
      recognizes the need of modeling different types of information and uncertainty
      that usually coexist in real environments. A home setting with sensors located in
      different rooms and on different appliances can be considered as a particularly
      relevant example of such an environment, which brings a range of challenges for
      sensor-based activity recognition. Although RIMER+ has been designed as a generic
      decision model that could be applied in a wide range of situations, this paper
      discusses how this methodology can be adapted to recognize human activities using
      binary sensors within smart environments. The evaluation of RIMER+ against other
      state-of-the-art classifiers in terms of accuracy, efficiency and applicability
      was found to be significantly relevant, specially in situations of input data
      incompleteness, and it demonstrates the potential of this methodology and
      underpins the basis to develop further research on the topic. 

PMID- 25570547
TI  - Closing the loop from continuous M-health monitoring to fuzzy logic-based
      optimized recommendations.
AB  - Continuous sensing of health metrics might generate a massive amount of data.
      Generating clinically validated recommendations, out of these data, to patients
      under monitoring is of prime importance to protect them from risk of falling into
      severe health degradation. Physicians also can be supported with automated
      recommendations that gain from historical data and increasing learning cycles. In
      this paper, we propose a Fuzzy Expert System that relies on data collected from
      continuous monitoring. The monitoring scheme implements preprocessing of data for
      better data analytics. However, data analytics implements the loopback feature in
      order to constantly improve fuzzy rules, knowledge base, and generated
      recommendations. Both techniques reduced data quantity, improved data quality and
      proposed recommendations. We evaluate our solution through a series of
      experiments and the results we have obtained proved that our fuzzy expert system
      combined with the intelligent monitoring and analytic techniques provide a high
      accuracy of collected data and valid advices. 

PMID- 25570548
TI  - Predicting postoperative acute respiratory failure in critical care using nursing
      notes and physiological signals.
AB  - Postoperative Acute Respiratory Failure (ARF) is a serious complication in
      critical care affecting patient morbidity and mortality. In this paper we
      investigate a novel approach to predicting ARF in critically ill patients. We
      study the use of two disparate sources of information - semi-structured text
      contained in nursing notes and investigative reports that are regularly recorded
      and the respiration rate, a physiological signal that is continuously monitored
      during a patient's ICU stay. Unlike previous works that retrospectively analyze
      complications, we exclude discharge summaries from our analysis envisaging a real
      time system that predicts ARF during the ICU stay. Our experiments, on more than
      800 patient records from the MIMIC II database, demonstrate that text sources
      within the ICU contain strong signals for distinguishing between patients who are
      at risk for ARF from those who are not at risk. These results suggest that large
      scale systems using both structured and unstructured data recorded in critical
      care can be effectively used to predict complications, which in turn can lead to
      preemptive care with potentially improved outcomes, mortality rates and decreased
      length of stay and cost.

PMID- 25570549
TI  - Predicting number of hospitalization days based on health insurance claims data
      using bagged regression trees.
AB  - Healthcare administrators worldwide are striving to both lower the cost of care
      whilst improving the quality of care given. Therefore, better clinical and
      administrative decision making is needed to improve these issues. Anticipating
      outcomes such as number of hospitalization days could contribute to addressing
      this problem. In this paper, a method was developed, using large-scale health
      insurance claims data, to predict the number of hospitalization days in a
      population. We utilized a regression decision tree algorithm, along with
      insurance claim data from 300,000 individuals over three years, to provide
      predictions of number of days in hospital in the third year, based on medical
      admissions and claims data from the first two years. Our method performs well in
      the general population. For the population aged 65 years and over, the predictive
      model significantly improves predictions over a baseline method (predicting a
      constant number of days for each patient), and achieved a specificity of 70.20%
      and sensitivity of 75.69% in classifying these subjects into two categories of
      'no hospitalization' and 'at least one day in hospital'.

PMID- 25570551
TI  - A study of activity and body posture with the PiiX mobile body-adherent device.
AB  - Remote monitoring of in-home activity and body posture provides useful
      physiological parameters for understanding patient status and for making clinical
      judgment in patients living with heart failure. The Corventis PiiX is a mobile
      chest-adherent device that provides continuously recorded accelerometer data from
      patients in an in-home setting. In particular, a 3-axis accelerometer enables
      quantification of full body activity and body posture changes. In this paper, the
      prevalence of sedentary activity with subject age, the population-wide
      distribution of upright body posture and resting body posture, and a diagnostic
      for reduced activity levels and resting body posture is presented with
      retrospective analysis on a large nonrandomized dataset. 

PMID- 25570550
TI  - Identifying and extracting patient smoking status information from clinical
      narrative texts in Spanish.
AB  - In this work we present a system to identify and extract patient's smoking status
      from clinical narrative text in Spanish. The clinical narrative text was
      processed using natural language processing techniques, and annotated by four
      people with a biomedical background. The dataset used for classification had
      2,465 documents, each one annotated with one of the four smoking status
      categories. We used two feature representations: single word token and bigrams.
      The classification problem was divided in two levels. First recognizing between
      smoker (S) and non-smoker (NS); second recognizing between current smoker (CS)
      and past smoker (PS). For each feature representation and classification level,
      we used two classifiers: Support Vector Machines (SVM) and Bayesian Networks
      (BN). We split our dataset as follows: a training set containing 66% of the
      available documents that was used to build classifiers and a test set containing
      the remaining 34% of the documents that was used to test and evaluate the model.
      Our results show that SVM together with the bigram representation performed
      better in both classification levels. For S vs NS classification level
      performance measures were: ACC=85%, Precision=85%, and Recall=90%. For CS vs PS
      classification level performance measures were: ACC=87%, Precision=91%, and
      Recall=94%. 

PMID- 25570552
TI  - Flexing bed stock: a hospital capacity management case study.
AB  - As hospitals struggle to meet rising demand for their services, efficient
      capacity management is critical to the success of their efforts. A popular
      strategy employed by hospitals to meet the variability in demand for their
      services is to 'flex' their capacity, i.e. to vary the number of available
      staffed beds to suit demand on a regular basis. This study uses data from a large
      tertiary hospital in South Australia to analyze the efficacy of their flexing
      protocols and the impact of flexing capacity on overcrowding. We also analyze the
      impact of variation in occupancy on patient flow parameters and compare this to
      previous studies conducted on similar sized Australian hospitals that do not flex
      capacity. Our findings reveal that flexing capacity helps the hospital spend less
      time over critical occupancy levels, and that the hospital does not show the
      signs of performance decline exhibited by hospitals that do not flex capacity.
      Areas for improvements in the flexing protocol and possible strategies are also
      identified. The findings support the use of flexing capacity as an efficient
      protocol and will serve as a useful guide for services seeking to improve
      existing capacity management protocols.

PMID- 25570553
TI  - A temporal interestingness measure for drug interaction signal detection in post
      marketing surveillance.
AB  - Drug-drug interactions (DDIs) can result in serious consequences, including
      death. Existing methods for identifying potential DDIs in post-marketing
      surveillance primarily rely on the FDA's (Food and Drug Administration)
      spontaneous reporting system. However, this system suffers from severe
      underreporting, which makes it difficult to timely collect enough valid cases for
      statistical analysis. In this paper, we study how to signal potential DDIs using
      patient electronic health data. Specifically, we focus on discovery of potential
      DDIs by analyzing the temporal relationships between the concurrent use of two
      drugs of interest and the occurrences of various symptoms using novel temporal
      association mining techniques we developed. A new interestingness measure called
      functional temporal interest was proposed to assess the degrees of temporal
      association between two drugs of interest and each symptom. The measure was
      employed to screen potential DDIs from 21,405 electronic patient cases retrieved
      from the Veterans Affairs Medical Center in Detroit, Michigan. The preliminary
      results indicate the usefulness of our method in finding potential DDIs for
      further analysis (e.g., epidemiology study) and investigation (e.g., case review)
      by drug safety professionals. 

PMID- 25570554
TI  - Personalization algorithms applied to cardiovascular disease risk assessment.
AB  - Cardiovascular disease (CVD) is the major cause of death in the world. Clinical
      guidelines recommend the use of risk assessment tools (scores) to identify the
      CVD risk of each patient as the correct stratification of patients may
      significantly contribute to the optimization of the health care strategies. This
      work further explores the personalization of CVD risk assessment, supported on
      the evidence that a specific CVD risk assessment tool may have good performance
      within a given group of patients and might perform poorly within other groups.
      Two main personalization methods based on the proper creation of groups of
      patients are presented: i) clustering patients approach; ii) similarity measures
      approach. These two methodologies were validated in a Portuguese population (460
      Acute Coronary Syndrome with non-ST segment elevation (ACS-NSTEMI) patients). The
      similarity measures approach had the best performance, achieving maximum values
      of sensitivity, specificity and geometric mean of, respectively, 77.7%, 63.2%,
      69.7%. These values represent an enhancement in relation to the best performance
      obtained with current CVD risk assessment tools applied in clinical practice
      (78.5%, 53.2%, 64.4%). 

PMID- 25570555
TI  - Comparison of arrhythmia prevalence in NUVANT Mobile Cardiac Telemetry System
      patients in the US and India.
AB  - The Corventis NUVANTTM Mobile Cardiac Telemetry System provides continuous
      monitoring of symptomatic and asymptomatic cardiac abnormalities to help
      physicians diagnose and treat non-lethal cardiac arrhythmias. Analysis of a
      sample of 2231 US and 1053 Indian NUVANT patients has revealed interesting
      statistics on the prevalence of various cardiac arrhythmias in the patient
      populations of the two nations. The population is non-randomized and consists of
      US patients where often a traditional Holter Monitor study was negative and self
      pay Indian patients. Mean age was 61.3 for the US and 57.8 for India with 57% of
      US patients and 32% of India patients being female. Presentation of specific
      arrhythmia types was similar across populations with the exception of atrial
      fibrillation and flutter being more prevalent in the older US population as well
      as increased prevalence of symptomatic atrial and ventricular ectopic rhythms in
      all patients and SVT for female patients in India. Utilization as defined by the
      number of patient triggers was 50% higher for Indian patients. 

PMID- 25570556
TI  - Precise prediction for managing chronic disease readmissions.
AB  - Potentially preventable hospital readmissions have a crippling effect on the
      health of chronic disease patients and on healthcare funding and resource
      utilization. While several prediction models have been proposed to help identify
      and manage high risk patients, most offer only moderate predictive power and
      discriminative ability. We develop and validate several models that utilize
      cohort population and clinical data and are capable of precisely identifying
      chronic disease patients with a high risk of rehospitalization within 30 days.
      Cross validation and receiver operating characteristic curve analysis are used to
      examine the predictive power of the models. The developed models offer high
      precision and discrimination and outperform current state of the art models.
      Delivering between 73% and 79% sensitivity at 93% specificity, the models offer
      excellent candidate prediction algorithms for the battle against the burden of
      chronic disease on the public health system. 

PMID- 25570557
TI  - A new on-line electrocardiographic records database and computer routines for
      data analysis.
AB  - Gathering experimental data to test computer methods developed during a research
      is a hard work. Nowadays, some databases have been stored online that can be
      freely downloaded, however there is not a wide range of databases yet and not all
      pathologies are covered. Researchers with low resources are in need of more data
      they can consult for free. To cope with this we present an on-line portal
      containing a compilation of ECG databases recorded over the last two decades for
      research purposes. The first version of this portal contains four databases of
      ECG records: ischemic cardiopathy (72 patients, 3-lead ECG each), ischemic
      preconditioning (20 patients, 3-lead ECG each), diabetes (51 patients, 8-lead ECG
      each) and metabolic syndrome (25 subjects, 12-lead ECG each). In addition, one
      computer program and three routines are provided in order to correctly read the
      signals, and two digital filters along with two ECG waves detectors are provided
      for further processing. This portal will be constantly growing, other ECG
      databases and signal processing software will be uploaded. With this project, we
      give the scientific community a resource to avoid hours of data collection and to
      develop free software. 

PMID- 25570558
TI  - Developing pressure sensitive adhesive electrodes: preliminary results.
AB  - A mixture of carbon black powder, polar organo salt and a pressure sensitive
      adhesive (PSA) has shown to be able to collect skin bio potentials. Such PSA
      electrodes do not dehydrate even after a prolonged period of storage, which leads
      to a theoretically infinite shelf life. The PSA electrodes need to be
      electrically activated through electrophoresis. ECG data were simultaneously
      collected with PSA and Ag-AgCl electrodes from 5 healthy subjects. ECG morphology
      was almost identical for both media. Hence, given that PSA electrodes have an
      infinite shelf-life, potentially with less cost associated with their
      fabrication, and have ECG signal dynamics nearly identical to those of Ag-AgCl,
      the new electrodes provide an attractive alternative for ECG measurements. 

PMID- 25570559
TI  - An on-chip system to monitor the pH of cell culture media.
AB  - We presents an ion sensitive field effect transistor to measure the pH of the
      cell culture media of human mammary adenocarcinoma (SKBR3). We use a drift
      mitigation technique that cycles the transistor to reset the drift in the system.
      We use to technique in the system to demonstrate an integrated system to monitor
      the pH continuously. As a part of the system a pulse width modulation circuit is
      designed in a 0.5 MUm CMOS process which cycles the vertical electric field of
      the ion sensitive field effect transistor to reset the threshold voltage drift.
      We demonstrate the viability of a complete integrated system implementing our
      drift mitigation technique to monitor cultured cells. The integration is
      important in this application to allow for autonomous operation inside an
      incubator during cell culture. 

PMID- 25570560
TI  - A programmable acoustic stimuli and auditory evoked potential measurement system
      for objective tinnitus diagnosis research.
AB  - This paper presents the development of a single platform that records auditory
      evoked potential synchronized to specific acoustic stimuli of the gap prepulse
      inhibition method for objective tinnitus diagnosis research. The developed system
      enables to program various parameters of the generated acoustic stimuli.
      Moreover, only by simple filter modification, the developed system provides high
      flexibility to record not only short latency auditory brainstem response but also
      late latency auditory cortical response. The adaptive weighted averaging
      algorithm to minimize the time required for the experiment is also introduced.
      The results show that the proposed algorithm can reduce the number of the
      averaging repetitions to 70% compared with conventional ensemble averaging
      method. 

PMID- 25570561
TI  - Multimodal physiological sensor for motion artefact rejection.
AB  - This work introduces a novel physiological sensor, which combines electrical and
      mechanical modalities in a co-located arrangement, to reject motion-induced
      artefacts. The mechanically sensitive element consists of an electret condenser
      microphone containing a light diaphragm, allowing it to detect local mechanical
      displacements and disregard large-scale whole body movements. The electrically
      sensitive element comprises a highly flexible membrane, conductive on one side
      and insulating on the other. It covers the sound hole of the microphone, thereby
      forming an isolated pocket of air between the membrane and the diaphragm. The co
      located arrangement of the modalities allows the microphone to sense mechanical
      disturbances directly through the electrode, thus providing an accurate proxy to
      artefacts caused by relative motion between the skin and the electrode. This
      proxy is used to reject such artefacts in the electrical physiological signals,
      enabling enhanced recording quality in wearable health applications. 

PMID- 25570562
TI  - Development of a diagnostic device to detect different Pseudomonas aeruginosa
      phenotypes in medically relevant contexts.
AB  - Pseudomonas aeruginosa, widely present in the environment, is well known for its
      ability to cause infection in immune compromised individuals. For example, P.
      aeruginosa is the leading cause of morbidity and mortality in patients with
      cystic fibrosis (CF). Here, we describe how Electrochemical Impedance
      Spectroscopy (EIS) can be used to detect the presence of four different strains
      of P. aeruginosa. Using a low cost, screen printed carbon electrode significant
      changes can be seen in impedance data in the presence of P. aeruginosa after 24
      hours. Furthermore, through the use of a normalization technique whereby the
      phase angle of the impedance (a commonly used parameter) is divided by a starting
      measurement, it is possible to identify differences between a non-mucoid and
      mucoid strain of P. aeruginosa. Sensors based upon the techniques described here
      could be used in a number of healthcare scenarios, where there is a need for low
      cost, real time detection of P. aeruginosa, such as CF. 

PMID- 25570563
TI  - "Sonocytometry" - novel diagnostic method of ultrasonic differentiation of cells
      in blood flow.
AB  - Novel diagnostic method named "sonocytometry", in which streaming blood cell is
      diagnosed by the reflection of high frequency ultrasound from the cell, is
      proposed. In the present study, the differentiation of the particle size is
      performed as a basic study on sonocytometry. Ultrasonic backscatter signal from
      either 80 or 100 MUm diameter polystyrene particles was measured by an ultrasonic
      transducer with the central frequency of 30 MHz. The spectrum of the reflected
      signal showed different characteristics according to the particle diameter.
      Theoretical value of backscatter was calculated by Faran-Hickling model and the
      correlation coefficient of measured and theoretical value by varying the
      spherical diameter showed the local maximum value at either 80 or 100 MUm
      diameter. The principle was also validated on the streaming particles in a flow
      channel. The method successfully classified the particle size. Sonocytometry
      would be clinically applied for diagnosis of malaria or leukemia. 

PMID- 25570564
TI  - High throughput single-ion-channel array microsystem with CMOS instrumentation.
AB  - Ion channels play critical roles in transporting chemical species into and out of
      cells. Ion channels are also targets for drug discovery and new receptor-based
      analytical technologies. To better understand ion channel structure and function,
      a high throughput membrane protein characterization microsystem is being
      developed. This microsystem integrates a 1024-element array of planar bilayer
      lipid membrane (pBLM) chambers with microfluidics and embedded CMOS
      electrochemical instrumentation circuits. This paper introduces the CMOS
      instrumentation circuits that support readout of 1024 pBLM elements in parallel
      and provide current pixel amplifiers within each cell for local amplification of
      the weak ion channel response currents. 

PMID- 25570565
TI  - Viscosity effect on the Brownian relaxation based detection for immunoassay
      applications.
AB  - Magnetic nanoparticles (MNPs) coated with Protein-G have been a model system to
      be used in different antibodies binding study. It is highly desirable to use a
      substrate-free biosensing system to detect antibodies binding in real-time. In
      this paper, we developed and applied a MNPs and search-coils integrated detection
      system, which is not only sensitive to the hydrodynamic volume of MNPs but also
      sensitive to the environment of MNPs, such as viscosity and temperature of the
      solution. We demonstrated that the viscosity effect influenced the amplitudes and
      phases of the 3rd (fH+/-2fL) and 5th (fH+/-4fL) harmonics for the mixed frequency
      testing scheme. The binding between antibodies and Protein-G on MNPs increased
      hydrodynamic volume of particles, as a result, it also changed the amplitudes and
      phases of harmonics, which are the object signals we need to analyze. We
      demonstrated that the viscosity of antibody solution is lower than that of MNP
      solution, and the antibody binding effect could be shielded by the viscosity
      effect to certain extent. 

PMID- 25570566
TI  - Voltage compensation based calibration measurement of 3D-acceleration transducer
      in fall detection system for the elderly.
AB  - The fall detection algorithm, which can recognize the fall of human body by
      collecting the acceleration signals in different directions of the body, is an
      important part of fall detection system for the elderly. The system, however, may
      have errors during analyzing the acceleration signal, due to that the coordinate
      system of the transducer does not coincide with the one of human motion.
      Furthermore, voltage variation of the battery also influences the accuracy of the
      acceleration signal. Therefore, in this paper, a fall detection system based on
      the 3D-acceleration transducer MMA7260 is designed, which can calibrate the
      acceleration data through compensation of voltage and transformation of
      coordinates. Experiments illustrated that the proposed method can accurately
      transform the collected data from the coordinate system of the transducer to that
      of the human motion, and can recognize various postural changes in the course of
      the motion of human body. 

PMID- 25570567
TI  - A flagellum based study of semiconductor nanofabrication through magnetotaxis.
AB  - Magnetospirillum magneticum (AMB-1), which belong to alpha-protobacterium are
      gram-negative, single-celled prokaryotic organisms consisting of a lash-like
      cellular appendage called flagella. These filamentous structures are made up of a
      protein called flagellin that in turn consist of four sub-domains, two inner
      domains (D0, D1) made up of alpha-helices and two outer domains (D2, D3) made up
      of beta sheets. It is wrapped in a helical fashion around the longitudinal
      filament with the outermost sub-domain (D3) exposed to the surrounding
      environment. This study focuses on the interaction of the D3 with semiconducting
      as well as metallic single-walled carbon nanotubes (m-SWNT) and in turn presents
      the interactive forces between the SWNT and D3 from the perspective of size and
      type of SWNT. It is found that the SWNT interacts the most with glycine and
      threonine residues of flagellin both electrostatically as well as through van der
      waals. Further, the viability of magnetotactic bacteria Magnetospirillum
      magneticum (AMB-1) in the presence of SWNT is experimentally investigated and it
      is found that magnetotaxis in AMB-1 is preserved without any toxic effects due to
      SWNT. It is proposed that AMB-1 can be used as an efficient carrier of carbon
      nanotubes through its flagellum for semiconductor nanofabrication tasks. 

PMID- 25570568
TI  - Characterization of a nanoscale S-layer protein based template for biomolecular
      patterning.
AB  - Well organized template for biomolecular conjugation is the foundation for
      biosensing. Most of the current devices are fabricated using lithographic
      patterning processes and self-assembly monolayer (SAM) methods. However, the
      research toward developing a sub-10 nm patterned, self-regenerated template on
      various types of substrates is limited, mainly due to the limited functional
      groups of the building material. Bacterial surface layer proteins (S-layer
      proteins) can self-assemble into ordered lattice with regular pore sizes of 2-8
      nm on different material supports and interfaces. The ordered structure can
      regenerate after extreme variations of solvent conditions. In this work, we
      developed a nanoscale biomolecular template based on S-layer proteins on gold
      surface for fabrication of sensing layer in biosensors. S-layer proteins were
      isolated from Bacillus cereus, Lysinibacillus sphaericus and Geobacillus
      stearothermophilus. Protein concentrations were measured by Bradford assay. The
      protein purities were verified by SDS-PAGE, showing molecular weights ranging
      from 97-135 kDa. The hydrophilicity of the substrate surface was measured after
      surface treatments of protein recrystallization. Atomic force microscopic (AFM)
      measurement was performed on substrate surface, indicating a successful
      immobilization of a monolayer of S-layer protein with 8-9 nm height on gold
      surface. The template can be applied on various material supports and acts as a
      self-regenerated sensing layer of biosensors in the future. 

PMID- 25570569
TI  - Individual cortical connectivity changes after stroke: a resampling approach to
      enable statistical assessment at single-subject level.
AB  - One of the main limitations commonly encountered when dealing with the estimation
      of brain connectivity is the difficulty to perform a statistical assessment of
      significant changes in brain networks at a single-subject level. This is mainly
      due to the lack of information about the distribution of the connectivity
      estimators at different conditions. While group analysis is commonly adopted to
      perform a statistical comparison between conditions, it may impose major
      limitations when dealing with the heterogeneity expressed by a given clinical
      condition in patients. This holds true particularly for stroke when seeking for
      quantitative measurements of the efficacy of any rehabilitative intervention
      promoting recovery of function. The need is then evident of an assessment which
      may account for individual pathological network configuration associated with
      different level of patients' response to treatment; such network configuration is
      highly related to the effect that a given brain lesion has on neural networks. In
      this study we propose a resampling-based approach to the assessment of
      statistically significant changes in cortical connectivity networks at a single
      subject level. First, we provide the results of a simulation study testing the
      performances of the proposed approach under different conditions. Then, to show
      the sensitivity of the method, we describe its application to
      electroencephalographic (EEG) data recorded from two post-stroke patients who
      showed different clinical recovery after a rehabilitative intervention. 

PMID- 25570570
TI  - Identification of brain networks using time-varying spatial constraints of neural
      activity reconstruction.
AB  - Electroencephalographic (EEG) data give a direct non-invasive measurement of
      neural brain activity. Nevertheless, the common assumption about EEG stationarity
      (time-invariant process) is a strong limitation for understanding real behavior
      of underlying neural networks. Here, we propose an approach for finding networks
      of brain regions connected by functional associations (functional connectivity)
      that vary along the time. To this end, we compute a set of a priori spatial
      dictionaries that represent brain areas with similar temporal stochastic
      dynamics, and then, we model relationship between areas as a time-varying
      process. We test our approach in both simulated and real EEG data where results
      show that inherent interpretability provided by the time-varying process can be
      useful to describe underlying neural networks. 

PMID- 25570571
TI  - A method for functional network connectivity using distance correlation.
AB  - In this paper, we present a novel approach for functional network connectivity in
      fMRI resting activity using distance correlation. The proposed method accounts
      for nonlinear relationships between the resting state networks and can be used
      for both single subject and group level analyses. We showed that the new strategy
      improves the capacity of characterization of pathological populations, such as,
      patients with disorder of consciousness, when compared to related approaches. 

PMID- 25570572
TI  - Impact of multivariate Granger causality analyses with embedded dimension
      reduction on network modules.
AB  - High dimensional functional MRI data in combination with a low temporal
      resolution imposes computational limits on classical Granger Causality analyses
      with respect to a large-scale representations of functional interactions in the
      brain. To overcome these limitations and exploit information inherent in
      resulting brain connectivity networks at the large scale, we propose a
      multivariate Granger Causality approach with embedded dimension reduction. Using
      this approach, we computed binary connectivity networks from resting state fMRI
      images and analyzed them with respect to network module structure, which might be
      linked to distinct brain regions with an increased density of particular
      interaction patterns as compared to inter-module regions. As a proof of concept,
      we show that the modular structure of these large-scale connectivity networks can
      be recovered. These results are promising since further analysis of large-scale
      brain network partitions into modules might prove valuable for understanding and
      tracing changes in brain connectivity at a more detailed resolution level than
      before. 

PMID- 25570573
TI  - Using static and dynamic canonical correlation coefficients as quantitative EEG
      markers for Alzheimer's disease severity.
AB  - We analyzed the relation between Alzheimer's disease (AD) severity as measured by
      Mini-Mental State Examination (MMSE) scores and quantitative
      electroencephalographic (qEEG) markers that were derived from canonical
      correlation analysis. This allowed an investigation of EEG synchrony between
      groups of EEG channels. In this study, we applied the data from 79 participants
      in the multi-centric cohort study PRODEM-Austria with probable AD. Following a
      homogeneous protocol, the EEG was recorded both in resting state and during a
      cognitive task. A quadratic regression model was used to describe the relation
      between MMSE and the qEEG synchrony markers. This relation was most significant
      in the delta and theta frequency bands in resting state, and between left
      hemispheric central, temporal and parietal channel groups during the cognitive
      task. Here, the MMSE explained up to 40% of the qEEG marker's variation. QEEG
      markers showed an ambiguous trend, i.e. an increase of EEG synchrony in the
      initial stage of AD (MMSE>20) and a decrease in later stages. This effect could
      be caused by compensatory brain mechanisms. We conclude that the proposed qEEG
      markers are closely related to AD severity. Despite the ambiguous trend and the
      resulting diagnostic ambiguity, the qEEG markers could provide aid in the
      diagnostics of early-stage AD.

PMID- 25570574
TI  - Periodicity in functional brain networks: application to scalp EEG from epilepsy
      patients.
AB  - Seizure detection and prediction studies using scalp- or intracranial-EEG
      measurements often focus on short-length recordings around the occurrence of the
      seizure, normally ranging between several seconds and up to a few minutes before
      and after the event. The underlying assumption in these studies is the presence
      of a relatively constant EEG activity in the interictal period, that is
      presumably interrupted by the occurrence of a seizure, at the time the seizure
      starts or slightly earlier. In this study, we put this assumption under test, by
      examining long-duration scalp EEG recordings, ranging between 22 and 72 hours, of
      five patients with epilepsy. For each patient, we construct functional brain
      networks, by calculating correlations between the scalp electrodes, and examine
      how these networks vary in time. The results suggest not only that the network
      varies over time, but it does so in a periodic fashion, with periods ranging
      between 11 and 25 hours. 

PMID- 25570575
TI  - Multiscale wavelet p-leader based heart rate variability analysis for survival
      probability assessment in CHF patients.
AB  - A priori discrimination of high mortality risk amongst congestive heart failure
      patients constitutes an important clinical stake in cardiology and involves
      challenging analyses of the temporal dynamics of heart rate variability (HRV).
      The present contribution investigates the potential of a new multifractal
      formalism, constructed on wavelet p-leader coefficients, to help discrimination
      between survivor and non survivor patients. The formalism, applied to a high
      quality database of 108 patients collected in a Japanese hospital, enables to
      assess the existence of multifractal properties amongst congestive heart failure
      patients and to reveal significant differences in the multiscale properties of
      HRV between survivor and non survivor patients, for scales ranging from
      approximately 60 to 250 beats. 

PMID- 25570576
TI  - Nearest-neighbor based wavelet entropy rate measures for intrapartum fetal heart
      rate variability.
AB  - The interpretation and analysis of intrapartum fetal heart rate (FHR), enabling
      early detection of fetal acidosis, remains a challenging signal processing task.
      The ability of entropy rate measures, amongst other tools, to characterize
      temporal dynamics of FHR variability and to discriminate non-healthy fetuses has
      already been massively investigated. The present contribution aims first at
      illustrating that a k-nearest neighbor procedure yields estimates for entropy
      rates that are robust and well-suited to FHR variability (compared to the more
      commonly used correlation-integral algorithm). Second, it investigates how
      entropy rates measured on multiresolution wavelet and approximation coefficients
      permit to improve classification performance. To that end, a supervised learning
      procedure is used, that selects the time scales at which entropy rates contribute
      to discrimination. Significant conclusions are obtained from a high quality scalp
      electrode database of nearly two thousands subjects collected in a French public
      university hospital. 

PMID- 25570577
TI  - Reliability of spectral analysis of fetal heart rate variability.
AB  - Spectral analysis of fetal heart rate variability could provide information on
      fetal wellbeing. Unfortunately, fetal heart rate recordings are often
      contaminated by artifacts. Correction of these artifacts affects the outcome of
      spectral analysis, but it is currently unclear what level of artifact correction
      facilitates reliable spectral analysis. In this study, a method is presented that
      estimates the error in spectral powers due to artifact correction, based on the
      properties of the Continuous Wavelet Transformation. The results show that it is
      possible to estimate the error in spectral powers. The information about this
      error makes it possible for clinicians to assess the reliability of spectral
      analysis of fetal heart rate recordings that are contaminated by artifacts. 

PMID- 25570578
TI  - Signal processing techniques for atrial fibrillation source detection.
AB  - In clinical practice, Atrial Fibrillation (AF) is the most common and critical
      cardiac arrhythmia encountered. The treatment that can ensure permanent AF
      removal is catheter ablation, where cardiologists destroy the affected cardiac
      muscle cells with RF or Laser. In this procedure it is necessary to know exactly
      from which part of the heart AF triggers are originated. Various signal
      processing algorithms provide a strong tool to track AF sources. This study
      proposes, signal processing techniques that can be exploited for
      characterization, analysis and source detection of AF signals. These algorithms
      are implemented on Electrocardiogram (ECG) and intracardiac signals which contain
      important information that allows the analysis of anatomic and physiologic
      aspects of the whole cardiac muscle. 

PMID- 25570579
TI  - Multi-modal causality analysis of eyes-open and eyes-closed data from
      simultaneously recorded EEG and MEG.
AB  - Owing to the recent advances in multi-modal data analysis, the aim of the present
      study was to analyze the functional network of the brain which remained the same
      during the eyes-open (EO) and eyes-closed (EC) resting task. The simultaneously
      recorded electroencephalogram (EEG) and magnetoencephalogram (MEG) were used for
      this study, recorded from five distinct cortical regions of the brain. We focused
      on the 'alpha' functional network, corresponding to the individual peak frequency
      in the alpha band. The total data set of 120 seconds was divided into three
      segments of 18 seconds each, taken from start, middle, and end of the recording.
      This segmentation allowed us to analyze the evolution of the underlying
      functional network. The method of time-resolved partial directed coherence (tPDC)
      was used to assess the causality. This method allowed us to focus on the
      individual peak frequency in the 'alpha' band (7-13 Hz). Because of the
      significantly higher power in the recorded EEG in comparison to MEG, at the
      individual peak frequency of the alpha band, results rely only on EEG. The MEG
      was used only for comparison. Our results show that different regions of the
      brain start to 'disconnect' from one another over the course of time. The driving
      signals, along with the feedback signals between different cortical regions start
      to recede over time. This shows that, with the course of rest, brain regions
      reduce communication with each another.

PMID- 25570580
TI  - Robustness of time frequency distribution based features for automated neonatal
      EEG seizure detection.
AB  - In this paper we examined the robustness of a feature-set based on time-frequency
      distributions (TFDs) for neonatal EEG seizure detection. This feature-set was
      originally proposed in literature for neonatal seizure detection using a support
      vector machine (SVM). We tested the performance of this feature-set with a
      smoothed Wigner-Ville distribution and modified B distribution as the underlying
      TFDs. The seizure detection system using time-frequency signal and image
      processing features from the TFD of the EEG signal using modified B distribution
      was able to achieve a median receiver operator characteristic area of 0.96 (IQR
      0.91-0.98) tested on a large clinical dataset of 826 h of EEG data from 18 full
      term newborns with 1389 seizures. The mean AUC was 0.93. 

PMID- 25570581
TI  - A fast SPAD-based small animal imager for early-photon diffuse optical
      tomography.
AB  - Photon scatter is the dominant light transport process in biological tissue and
      is well understood to degrade imaging performance in near-infrared diffuse
      optical tomography. Measurement of photons arriving at early times following a
      short laser pulse is considered to be an effective method to improve this
      limitation, i.e. by systematically selecting photons that have experienced fewer
      scattering events. Previously, we tested the performance of single photon
      avalanche photodiode (SPAD) in measurement of early transmitted photons through
      diffusive media and showed that it outperformed photo-multiplier tube (PMT)
      systems in similar configurations, principally due to its faster temporal
      response. In this paper, we extended this work and developed a fast SPAD-based
      time-resolved diffuse optical tomography system. As a first validation of the
      instrument, we scanned an optical phantom with multiple absorbing inclusions and
      measured full time-resolved data at 3240 scan points per axial slice. We
      performed image reconstruction with very early-arriving photon data and showed
      significant improvements compared to time-integrated data. Extension of this work
      to mice in vivo and measurement of time-resolved fluorescence data is the subject
      of ongoing research. 

PMID- 25570582
TI  - Scaling up multiphoton neural scanning: the SSA algorithm.
AB  - In order to reverse-engineer the information processing capabilities of the
      cortical circuit, we need to densely sample neural circuit; it may be necessary
      to sample the activity of thousands of neurons simultaneously. Frame scanning
      techniques do not scale well in this regard, due to the time "wasted" scanning
      extracellular space. For scanners in which inertia can be neglected, path length
      minimization strategies enable large populations to be imaged at relatively high
      sampling rates. However, in a standard multiphoton microscope, the scanners
      responsible for beam deflection are inertial, indicating that an optimal solution
      should take rotor and mirror momentum into account. We therefore characterized
      the galvanometric scanners of a commercial multiphoton microscope, in order to
      develop and validate a MATLAB model of microscope scanning dynamics. We tested
      the model by simulating scan paths across pseudo-randomly positioned neuronal
      populations of differing neuronal density and field of view. This model motivated
      the development of a novel scanning algorithm, Adaptive Spiral Scanning (SSA), in
      which the radius of a circular trajectory is constantly updated such that it
      follows a spiral trajectory scanning all the cells. Due to the kinematic
      efficiency of near-circular trajectories, this algorithm achieves higher sampling
      rates than shortest path approaches, while retaining a relatively efficient
      coverage fraction in comparison to raster or resonance based frame-scanning
      approaches. 

PMID- 25570583
TI  - A sputum smear microscopy image database for automatic bacilli detection in
      conventional microscopy.
AB  - In this work, we present an image database for automatic bacilli detection in
      sputum smear microscopy. The database comprises two parts. The first one, called
      the autofocus database, contains 1200 images with resolution of 2816 * 2112
      pixels. This database was obtained from 12 slides, with 10 fields per slide. Each
      stack is composed of 10 images, with the fifth image in focus. The second one,
      called the segmentation and classification database, contains 120 images with
      resolution of 2816*2112 pixels. This database was obtained from 12 slices, with
      10 fields per slice. In both databases, the images were acquired from fields of
      slides stained with the standard Kinyoun method. In both databases, accordingly
      to the background content, the images were classified as belonging to high
      background content or low background content. In all 120 images of segmentation
      and classification database, the identified objects were enclosed within a
      geometric shape by a trained technician. A true bacillus was enclosed in a
      circle. An agglomerated bacillus was enclosed by a rectangle and a doubtful
      bacillus (the image focus or geometry does not allow a clear identification of
      the object) was enclosed by a polygon. These marked objects could be used as a
      gold standard to calculate the accuracy, sensitivity and specificity of bacilli
      recognition. 

PMID- 25570584
TI  - Early artery blood flow is more prognostic in rodent model of middle cerebral
      artery occlusion.
AB  - Middle cerebral artery occlusion (MCAO) by intraluminal suture is one of the most
      commonly used stroke models. Our previous study has indicated that the
      intraoperative cerebral blood flow (CBF) immediately after the stroke is
      prognostic for long-term permanent injury. The area of more than 50% CBF drop at
      the first minute after the stroke was found significantly correlated with the
      lesion size at 24 hours after the stroke. In order to compare the prognostic of
      different vessels, in this study, we further analyzed the correlation between the
      CBF levels in major artery, vein and the capillary bed and the lesion volume at
      24 hours respectively. The results show that ipsilesional artery blood flow is of
      more prognostic value in MCAO lesion than the CBF in veins and capillaries. 

PMID- 25570585
TI  - Noninvasive determination of absorption and reduced scattering coefficients of
      adult heads by time-resolved reflectance measurements for functional near infra
      red spectroscopy.
AB  - Absorption and reduced scattering coefficients (MU(a) and MU'(s)) of adult heads
      have been noninvasively determined by time-resolved reflectance measurements. The
      finite difference time domain (FDTD) analysis was used to calculate time-resolved
      reflectance from realistic adult head models with brain grooves containing a non
      scattering layer. In vivo time-resolved reflectances of human heads were measured
      by a system composed of a time-correlated single photon counter and a diode
      laser. By minimizing the objective functions that compare theoretical and
      experimental time resolved reflectances, MU(a) and MU'(s) of brain were
      determined. It became clear that time-resolved measurements have enough
      sensitivity to determine both MU(a) and MU'(s) for superficial tissues, gray
      matter and white matter, except MU(s) for white matter.

PMID- 25570586
TI  - Simultaneous optical mapping system of endocardial and epicardial excitation.
AB  - The cardiac excitation propagation during arrhythmia shows a three-dimensional
      complex excitation behavior. Numerous optical measurements of the propagation and
      action potentials of the cardiac muscles have been made to elucidate the detailed
      arrhythmia phenomenon. The conventional optical measurement system mainly
      observes the action potential signal of the epicardium, and the endocardial
      signal measurement without incising the heart is difficult. In addition, an
      incised heart no longer exhibits the natural excitation behavior. Therefore, we
      constructed a simultaneous measurement system that integrates the conventional
      epicardial measurement system and the endocardial measurement system by using an
      endoscope for an intact heart. Then, we proposed a line-laser registration method
      that can match correspondence between the epicardial and endocardial images for a
      short period. We demonstrated that this registration method has a sub-millimeter
      accuracy. Subsequently, we succeeded in simultaneous optical measurement of the
      excitation propagation of the epicardium and endocardium of the right heart wall
      by using an isolated rabbit heart. 

PMID- 25570587
TI  - Three dimensional shear wave elastographic reconstruction of ablations.
AB  - This paper presents an algorithm for three dimensional (3D) reconstruction of
      tumor ablations using ultrasound electrode vibration elastography. Shear wave
      velocity, which is used as a surrogate for tissue stiffness, is estimated by
      perturbing the ablation needle and tracking frame-to-frame displacements using
      radiofrequency ultrasound echo data. This process is repeated over many imaging
      planes that share a common axis of intersection collinear with needle. A 3D
      volume is reconstructed by solving an optimization problem which smoothly
      approximates shear wave velocities on a stack of transverse planes. The mean
      shear wave velocity estimates obtained in the phantom experiments are within 20%
      of those measured using a commercial shear wave imaging system. 

PMID- 25570588
TI  - Stochastic piecewise linear function fitting with application to ultrasound shear
      wave imaging.
AB  - Piecewise linear function fitting is ubiquitous in many signal processing
      applications. Inspired by an application to shear wave velocity imaging in
      ultrasound elastography, this paper presents a discrete state-space Markov model
      for noisy piecewise linear data and also proposes a tractable algorithm for
      maximum a posteriori estimation of the slope of each segment in the piecewise
      linear function. The number and locations of breaks is handled indirectly by the
      stochastics of the Markov model. In the ultrasound shear wave imaging
      application, these slope values have concrete physical interpretation as being
      the reciprocal of the shear wave velocities in the imaged medium. Data acquired
      on an ellipsoidal inclusion phantom shows that this algorithm can provide good
      contrast of around 6 dB and contrast to noise ratio of 25 dB between the stiff
      inclusion and surrounding soft background. The phantom validation study also
      shows that this algorithm can be used to preserve sharp boundary details, which
      would otherwise be blurred out if a sliding window least squares filter is
      applied. 

PMID- 25570589
TI  - Improved mass detection in 3D automated breast ultrasound using region based
      features and multi-view information.
AB  - Breast cancer is one of the leading causes of cancer death for women. Early
      detection of breast cancer is crucial for reducing mortality rates and improving
      prognosis of patients. Recently, 3D automated breast ultrasound (ABUS) has gained
      increasing attentions for reducing subjectivity, operator-dependence, and
      providing 3D context of the whole breast. In this work, we propose a breast mass
      detection algorithm improving voxel-based detection results by incorporating 3D
      region-based features and multi-view information in 3D ABUS images. Based on the
      candidate mass regions produced by voxel-based method, our proposed approach
      further improves the detection results with three major steps: 1) 3D mass
      segmentation in geodesic active contours framework with edge points obtained from
      directional searching; 2) region-based single-view and multi-view feature
      extraction; 3) support vector machine (SVM) classification to discriminate
      candidate regions as breast masses or normal background tissues. 22 patients
      including 51 3D ABUS volumes with 44 breast masses were used for evaluation. The
      proposed approach reached sensitivities of 95%, 90%, and 70% with averaged 4.3,
      3.8, and 1.6 false positives per volume, respectively. The results also indicate
      that the multi-view information plays an important role in false positive
      reduction in 3D breast mass detection. 

PMID- 25570590
TI  - A hybrid method towards automated nipple detection in 3D breast ultrasound
      images.
AB  - In clinical work-up of breast cancer, nipple position is an important marker to
      locate lesions. Moreover, it serves as an effective landmark to register a 3D
      automated breast ultrasound (ABUS) images to other imaging modalities, e.g., X
      ray mammography, tomosynthesis or magnetic resonance imaging (MRI). However, the
      presence of speckle noises caused by the interference waves and variant imaging
      directions poses challenges to automatically identify nipple positions. In this
      work, a hybrid fully automatic method to detect nipple positions in ABUS images
      is presented. The method extends the multi-scale Laplacian-based method that we
      proposed previously, by integrating a specially designed Hessian-based method to
      locate the shadow area beneath the nipple and areola. Subsequently, the
      likelihood maps of nipple positions generated by both methods are combined to
      build a joint-likelihood map, where the final nipple position is extracted. To
      validate the efficiency and robustness, the extended hybrid method was tested on
      926 ABUS images, resulting in a distance error of 7.08+/-10.96 mm (mean+/
      standard deviation). 

PMID- 25570591
TI  - Data acquisition system for harmonic motion microwave Doppler imaging.
AB  - Harmonic Motion Microwave Doppler Imaging (HMMDI) is a hybrid method proposed for
      breast tumor detection, which images the coupled dielectric and elastic
      properties of the tissue. In this paper, the performance of a data acquisition
      system for HMMDI method is evaluated on breast phantom materials. A breast fat
      phantom including fibro-glandular and tumor phantom regions is produced. The
      phantom is excited using a focused ultrasound probe and a microwave transmitter.
      The received microwave signal level is measured on three different points inside
      the phantom (fat, fibro-glandular, and tumor regions). The experimental results
      using the designed homodyne receiver proved the effectiveness of the proposed
      setup. In tumor phantom region, the signal level decreased about 3 dB compared to
      the signal level obtained from the fibro-glandular phantom area, whereas this
      signal was about 4 dB higher than the received signal from the fat phantom. 

PMID- 25570592
TI  - Effects of key parameters on the accuracy and precision of local pulse wave
      velocity measurement by ultrasound imaging.
AB  - Quantification of arterial stiffness, such as pulse wave velocity (PWV), is
      increasingly used in the risk assessment of cardiovascular disease. Pulse wave
      imaging (PWI) is an emerging ultrasound-based technique to noninvasively measure
      the local PWV, instead of the global PWV as in conventional methods. In PWI,
      several key parameters, including the frame rate, number of scan lines, image
      width and PWV, play an important but still unclear role in the accuracy and
      precision of PWV measurement. In this study, computer simulations were performed
      to investigate the fundamental effects of these parameters on the PWV estimation.
      By applying different time delays on the pre-obtained pulse waveform based on
      specific PWI parameters, the pulse wave propagation along the artery was
      simulated and the ultrasound RF signals were generated from a convolutional image
      formation model. The PWI technique was applied to calculate the PWV at different
      values of key parameters. The performance is evaluated by measuring the bias,
      standard deviation (SD) and coefficient of determination (R(2)) of the estimated
      PWVs. The results show that PWVs can be correctly measured when the frame rate is
      higher than a certain value, below which the estimated PWVs become inaccurate.
      The SD decreases while R(2) increases with number of scan lines and image width,
      indicating a better performance of the PWV estimation with a larger number of
      scan lines and image width. A higher value of PWV is found to deteriorate the PWV
      estimation. The quantitative effects of the key parameters obtained from this
      study may provide important guidelines for optimization of PWI parameters in
      vivo. 

PMID- 25570593
TI  - Atlas based AAM and SVM model for fully automatic MRI prostate segmentation.
AB  - Automatic prostate segmentation in MR images is a challenging task due to inter
      patient prostate shape and texture variability, and the lack of a clear prostate
      boundary. We propose a supervised learning framework that combines the atlas
      based AAM and SVM model to achieve a relatively high segmentation result of the
      prostate boundary. The performance of the segmentation is evaluated with cross
      validation on 40 MR image datasets, yielding an average segmentation accuracy
      near 90%. 

PMID- 25570594
TI  - Prostate boundary segment extraction using cascaded shape regression and optimal
      surface detection.
AB  - In this paper, we proposed a new method (CSR+OSD) for the extraction of irregular
      open prostate boundaries in noisy extracorporeal ultrasound image. First,
      cascaded shape regression (CSR) is used to locate the position of prostate
      boundary in the images. In CSR, a sequence of random fern predictors are trained
      in a boosted regression manner, using shape-indexed features to achieve
      invariance against position variations of prostate boundaries. Afterwards, we
      adopt optimal surface detection (OSD) to refine the prostate boundary segments
      across 3D sections globally and efficiently. The proposed method is tested on 162
      ECUS images acquired from 8 patients with benign prostate hyperplasia. The method
      yields a Root Mean Square Distance of 2.11+/-1.72 mm and a Mean Absolute Distance
      of 1.61+/-1.26 mm, which are lower than those of JFilament, an open active
      contour algorithm and Chan-Vese region based level set model, respectively. 

PMID- 25570595
TI  - Shape-based kidney detection and segmentation in three-dimensional abdominal
      ultrasound images.
AB  - Due to recent technical advancements of three-dimensional ultrasound imaging
      systems, applications of this imaging modality have been expanding from the fetal
      imaging to cardiac- and abdominal-diagnosis. Among all internal organs,
      diagnosing the kidney has a paramount importance for rapid bedside treatment of
      trauma and kidney stone patients using ultrasound images. Although three
      dimensional ultrasound provides higher level of structural information of
      kidneys, manual kidney diagnosis using three-dimensional ultrasound images
      requires a highly trained medical staff, due to the extensive visual complexity
      which three-dimensional images contain. Therefore, computer aided automated
      kidney diagnosis becomes very essential. Due to the challenging problems of
      ultrasound images, such as speckle noise and inhomogeneous intensity profile,
      kidney segmentation in three-dimensional ultrasound images has not been
      sufficiently investigated by researchers. In this paper, we first propose a new
      automated kidney detection approach using three-dimensional Morison's pouch
      ultrasound images. Then, we proposed a shape-based method to segment the detected
      kidneys. A preprocessing step is utilized to overcome the ultrasound challenges.
      Based on a set of 14 ultrasound volumes, we have evaluated the detection rate of
      our proposed kidney detection approach which is 92.86%. For kidney segmentation,
      we compared our proposed method with an existing approach, and the performed
      statistical analysis strongly validates the superiority of our proposed method
      with p = 0.000032. 

PMID- 25570596
TI  - Kernel-based atlas image selection for brain tissue segmentation.
AB  - We propose a new Kernel-based Atlas Image Selection computed in the Embedding
      Representation space (termed KAISER) aiming to support labeling of brain tissue
      on 3D magnetic resonance (MR) images. KAISER approach provides efficient feature
      extraction from MR volumes based on an introduced inter-slice kernel (ISK). Thus,
      using the ISK matrix eigendecomposition, the inherent structure of data
      distribution is accentuated through estimation of low dimensional compact space
      where every pair-wise image similarity can be better measured. We compare our
      proposal against the whole-population atlas, randomly and demographically
      selected multiatlas approaches in a four-tissue image labeling task. Obtained
      results show that the KAISER approach outperforms other alternative techniques
      (98% Dice index similarity against 94%), while exhibiting better repeatability. 

PMID- 25570597
TI  - Efficient ribcage segmentation from CT scans using shape features.
AB  - Rib cage structure and morphology is important for anatomical analysis of chest
      CT scans. A fundamental challenge in rib cage extraction is varying intensity
      levels and connection with adjacent bone structures including shoulder blade and
      sternum. In this study, we present a fully automated 3-D algorithm to segment the
      rib cage by detection and separation of other bone structures. The proposed
      approach consists of four steps. First, all high-intensity bone structures are
      segmented. Second, multi-scale Hessian analysis is performed to capture plateness
      and vesselness information. Third, with the plate/vessel features, bone
      structures other than rib cage are detected. Last, the detected bones are
      separated from rib cage with iterative relative fuzzy connectedness method. The
      algorithm was evaluated using 400 human CT scans and 100 small animal images with
      various resolution. The results suggested that the percent accuracy of rib cage
      extraction is over 95% with the proposed algorithm. 

PMID- 25570598
TI  - A deep learning based framework for accurate segmentation of cervical cytoplasm
      and nuclei.
AB  - In this paper, a superpixel and convolution neural network (CNN) based
      segmentation method is proposed for cervical cancer cell segmentation. Since the
      background and cytoplasm contrast is not relatively obvious, cytoplasm
      segmentation is first performed. Deep learning based on CNN is explored for
      region of interest detection. A coarse-to-fine nucleus segmentation for cervical
      cancer cell segmentation and further refinement is also developed. Experimental
      results show that an accuracy of 94.50% is achieved for nucleus region detection
      and a precision of 0.9143+/-0.0202 and a recall of 0.8726+/-0.0008 are achieved
      for nucleus cell segmentation. Furthermore, our comparative analysis also shows
      that the proposed method outperforms the related methods. 

PMID- 25570599
TI  - Career imperative. Is it legal? Is it ethical?
AB  - This paper gives sample ethical case vignettes and discussions that will be
      presented at the 36th Annual International Conference of the IEEE Engineering in
      Medicine and Biology Society (EMBC'14) special session of the Ethics and
      Professional Responsibility Committee. The session includes additional cases with
      audience participation and panel discussions. 

PMID- 25570600
TI  - A CMI (cell metabolic indicator)-based controller for achieving high growth rate
      Escherichia coli cultures.
AB  - A large fraction of biopharmaceuticals are produced in Escherichia coli, where
      each new product and strain currently requires a high degree of growth
      characterization in benchtop and industrial bioreactors to achieve economical
      production protocols. The capability to use a standard set of sensors to
      characterize a system quickly without the need to conduct numerous experiments to
      determine stable growth rate for the strain would significantly decrease
      development time. This paper presents a cell metabolic indicator (CMI) which
      provides better insight into the E. coli metabolism than a growth rate value. The
      CMI is the ratio of the oxygen uptake rate (OUR) of the culture and the base
      addition rate (BAR) required to keep pH at a desired setpoint. The OUR and BAR
      are measured using a off-gas sensor and pH probe, respectively, and thus the CMI
      can be computed online. Experimental results demonstrate the relationship between
      CMI and the different cell metabolic states. A previously published model is
      augmented with acid production dynamics, allowing for comparison of the CMI-based
      controller with an open-loop controller in simulation. The CMI-based controller
      required little a priori knowledge about the E. coli strain in order to achieve a
      high growth rate. Since many different types of cells exhibit similar behaviors,
      the CMI concept can be extended to mammalian and stem cells. 

PMID- 25570601
TI  - Nanograting structure promotes lamellipodia-based cell collective migration and
      wound healing.
AB  - Wound healing is a dynamic and complex process of replacing missing or dead cell
      structures and tissue layers. The aim of this research is to discover
      biocompatible materials and drugs that can promote cell migration in the wound
      area and thus enhance desirable wound healing effects. In this paper, we report
      that PDMS nanogratings could accelerate the migration of epithelial cells along
      the grating axis, and the addition of Imatinib could further increase the
      epithelial cell wound healing speed to 1.6 times the speed of control cells. We
      also demonstrate that this migration is mediated by lamellipodia protrusion, and
      is Rac1-GTPase activity dependent. Lastly, we discuss the potential application
      and prospect of different nanostructured biomaterials for wound healing studies. 

PMID- 25570602
TI  - Halloysite nanotube-based drug delivery system for treating osteosarcoma.
AB  - Our previous studies have shown that halloysite nanotubes (HNTs) can be doped
      with a variety of bioactive agents (antibiotics, growth factors,
      chemotherapeutics) and the agents can be released in a sustained manner. In this
      study, anti-tumor drugs were loaded into HNTs and tested for their ability to
      inhibit/kill osteosarcoma cells. Results demonstrate that drugs released from the
      HNTs can inhibit proliferation or induce apoptosis in the osteosarcoma cells
      showing the potential application of doped HNTs as an anti-cancer drug delivery
      system. 

PMID- 25570603
TI  - Agent-based modeling of osteogenic differentiation of mesenchymal stem cells in
      porous biomaterials.
AB  - Mesenchymal stem cells (MSC) have shown promise in tissue engineering
      applications due to their potential for differentiating into mesenchymal tissues
      such as osteocytes, chondrocytes, and adipocytes and releasing proteins to
      promote tissue regeneration. One application involves seeding MSCs in biomaterial
      scaffolds to promote osteogenesis in the repair of bone defects following
      implantation. However, predicting in vivo survival and differentiation of MSCs in
      biomaterials is challenging. Rapid and stable vascularization of scaffolds is
      required to supply nutrients and oxygen that MSCs need to survive as well as to
      go through osteogenic differentiation. The objective of this study is to develop
      an agent-based model and simulator that can be used to investigate the effects of
      using gradient growth factors on survival and differentiation of MSCs seeded in
      scaffolds. An agent-based model is developed to simulate the MSC behavior. The
      effect of vascular endothelial growth factor (VEGF) and bone morphogenic protein
      2 (BMP-2) on both survival and osteogenic differentiation is studied. Results
      showed that the survival ratio of MSCs can be enhanced by increasing VEGF
      concentration. BMP-2 caused a slight increase on survival ratio. Osteogenesis
      strongly depends on the VEGF concentration as well because of its effect on
      vascularization. BMP-2 increased the osteogenic differentiation of MSCs. 

PMID- 25570604
TI  - Increased hydrostatic pressure enhances motility of lung cancer cells.
AB  - Interstitial fluid pressures within most solid tumors are significantly higher
      than that in the surrounding normal tissues. Therefore, cancer cells must
      proliferate and migrate under the influence of elevated hydrostatic pressure
      while a tumor grows. In this study, we developed a pressurized cell culture
      device and investigated the influence of hydrostatic pressure on the migration
      speeds of lung cancer cells (CL1-5 and A549). The migration speeds of lung cancer
      cells were increased by 50-60% under a 20 mmHg hydrostatic pressure. We also
      observed that the expressions of aquaporin in CL1-5 and A549 cells were increased
      under the hydrostatic pressure. Our preliminary results indicate that increased
      hydrostatic pressure plays an important role in tumor metastasis. 

PMID- 25570605
TI  - Study of interactions between cells and microbubbles in high speed centrifugation
      field for biomolecule delivery.
AB  - Biomolecule delivery has a very wide range of applications in biology and
      medicine. In this study, a microbubble based delivery method was developed. In a
      high centrifugation field, cells deform and collide with microbubbles to induce
      intracellular pathways on cell membranes. As a result, biomaterials can then
      easily enter cells. Experimental results show that this delivery method can
      achieve high delivery efficiency. Simulation results showed that cells with more
      deformed structure experienced higher strain on cell membranes than cells with
      less deformed structure. The models can help explain how centrifugation affects
      cell membrane permeability. By controlling cell morphology and its mechanical
      properties, high biomolecule delivery efficiency can be achieved. 

PMID- 25570607
TI  - Assessment of baroreflex sensitivity by continuous noninvasive monitoring of
      peripheral and central aortic pressure.
AB  - Noninvasive assessment of baroreceptor sensitivity (BRS) facilitates clinical
      investigation of autonomic function. The spontaneous sequence method estimates
      BRS using the continuous measurement of arterial pressure in the finger. Since
      the baroreceptors are centrally located (aortic arch, carotid arteries), this
      study assessed the use of a continuous aortic pressure signal derived from the
      peripheral pressure pulse to compute the BRS from changes in systolic pressure
      (SBP) and pulse interval (PI). BRS computed from central aortic (cBRS) and
      peripheral pressure (pBRS) was calculated in 12 healthy subjects (25-62 years, 7
      females). The difference between pBRS and cBRS was calculated for four levels of
      pulse lags between changes in SBP and PI. For each lag and for the pooled data
      for all lags, cBRS was significantly correlated with pBRS (r(2)=0.82). The within
      subject difference ranged from -41.2% to 59.2%. This difference was not related
      to age, gender of hemodynamic parameters (systolic or diastolic pressure, heart
      rate, aortic pulse wave velocity). However 18.2% of the variance was due to the
      difference in the number of spontaneous pulse sequences used to determine values
      of cBRS and pBRS. The differences between pBRS and cBRS are in the range of
      values of BRS as those found, in other studies, to discriminate between patient
      groups with different levels of autonomic function. Findings of this study
      suggest that, given the heart rate dependent amplification of the arterial
      pressure pulse between the central aorta and the peripheral limbs, BRS determined
      from central aortic pressure derived from the peripheral pulse may provide an
      improved method for noninvasive assessment of baroreceptor function. 

PMID- 25570606
TI  - Estimating the baroreflex and respiratory modulation of peripheral vascular
      resistance.
AB  - The peripheral vascular resistance (RPV) control is known to be largely
      sympathetically-mediated; thus assessment of the RPV control would allow us to
      infer valuable information regarding sympathetic nervous activity. The linear and
      2nd-order nonlinear minimal models were used to capture the influences of blood
      pressure (baroreflex) and respiration (respiratory-coupling) on fluctuations of
      RPV. To validate the minimal models, they were applied on the "data" generated by
      the simulation model developed in our previous study. This study demonstrated
      that the linear minimal model was able to recover the "true" (simulated) kernels.
      The nonlinear model was able to detect the increase in nonlinearity in the
      system. The system gains derived from the estimated kernels showed strong
      relationship with the simulation gains, suggesting that the system gains could be
      employed as potential biomarkers of autonomic function. These results also showed
      that the nonlinear model had sufficient sensitivity to detect the difference in
      autonomic reactivity between subjects with mild and severe metabolic syndrome and
      obstructive sleep apnea syndrome exposed to orthostatic stress. 

PMID- 25570608
TI  - Field stimulation of the carotid baroreceptor complex does not compromise
      baroreceptor function in spontaneously hypertensive rats.
AB  - Field stimulation of the carotid baroreceptors has been successfully used to
      induce a long-term reduction in blood pressure. However, baroreceptor stimulation
      may interfere with or compromise the beneficial short-term blood pressure
      regulation function of the baroreceptors. This study aims to quantify the
      baroreceptor function before and during acute, unilateral field stimulation of
      the carotid baroreceptors. Spontaneously Hypertensive Rats (n=7) were
      anaesthetised and instrumented to measure heart rate and mean arterial pressure
      (MAP), aortic pulse wave velocity (a surrogate measure of arterial stiffness),
      abdominal aortic flow and renal artery flow. A custom made field stimulation
      device was fitted to the left common carotid artery. Baroreceptor function was
      measured by quantifying heart rate response to MAP change induced by bolus
      injection of phenylephrine. Field stimulation of the baroreceptors reduced heart
      rate by 20 bpm (p=0.003) with MAP reduction of 18 mmHg (p=0.008). Maximal
      barorecep-tor gain without stimulation was -1.20+/-0.41 bpm/mmHg and during
      stimulation -1.41+/-0.52 bpm/mmHg (p=0.59). The MAP at which maximal gain
      occurred also did not change (152+/-11, 160+/-9 mmHg respectively, p=0.22). This
      study indicates that unilateral field stimulation of the carotid baroreceptor
      complex, while causing a sustained reduction of arterial pressure, does not alter
      acute baroreceptor function peak gain. 

PMID- 25570609
TI  - Temporal trends of neuro-autonomic complexity during severe episodes of bipolar
      disorders.
AB  - Bipolar disorder is a chronic psychiatric condition during which patients
      experience mood swings among depression, hypomania or mania, mixed state
      (depression-hypomania) and euthymia, i.e., good affective balance. Nowadays, an
      objective characterization of the temporal trends of the disease as a response to
      the pharmacological treatment through physiological signatures, especially during
      severe episodes, is still missing. In this study we show interesting findings
      relating neuro-autonomic complexity to severe pathological mood states. More
      specifically, we studied Sample Entropy (SampEn) measures on Heart Rate
      Variability series gathered from four bipolar patients recruited within the frame
      of the European project PSYCHE. Patients were monitored through long term ECG
      recordings from the first hospital admission until clinical remission, i.e., the
      euthymic state. We observed that a mood transition from mixed-state to euthymia
      passing through depression can be characterized by increased SampEn values, i.e.
      as the patient is going to recover, SampEn increases. These results are in
      agreement with the current literature reporting on the complexity dynamics of the
      cardiovascular system and can provide a promising and viable clinical decision
      support to objectify the diagnosis and improve the management of psychiatric
      disorders. 

PMID- 25570610
TI  - A novel multi-parametric algorithm for faint prediction integrating indices of
      cardiac inotropy and vascular tone.
AB  - Neurally medicated syncope (NMS) patients suffer from sudden loss of
      consciousness, which is associated with a high rate of falls and hospitalization.
      NMS negatively impacts a subject's quality of life and is a growing cost issue
      for the healthcare systems in particular since mainly elderly are at risk of NMS
      in our aging societies. In the present paper we present an algorithm for
      prediction of NMS, which is based on the analysis of the electrocardiogram (ECG)
      and photoplethysmogram (PPG) signals. Several parameters extracted from ECG and
      PPG, which have been associated in previous works with reflectory mechanisms
      underlying NMS, were combined in a single algorithm to detect impending syncope.
      The proposed algorithm was validated in 43 subjects using a 3-way data split
      scheme and achieved the following performance: sensitivity (SE) - 100%;
      specificity (SP) - 92%; positive predictive value (PPV) - 85%; false positive
      rate per hour (FPRh) - 0.146h(-1) and; average prediction time (aPTime) -
      217.58s. 

PMID- 25570611
TI  - Remote measurement of cognitive stress via heart rate variability.
AB  - Remote detection of cognitive load has many powerful applications, such as
      measuring stress in the workplace. Cognitive tasks have an impact on breathing
      and heart rate variability (HRV). We show that changes in physiological
      parameters during cognitive stress can be captured remotely (at a distance of 3m)
      using a digital camera. A study (n=10) was conducted with participants at rest
      and under cognitive stress. A novel five band digital camera was used to capture
      videos of the face of the participant. Significantly higher normalized low
      frequency HRV components and breathing rates were measured in the stress
      condition when compared to the rest condition. Heart rates were not significantly
      different between the two conditions. We built a person-independent classifier to
      predict cognitive stress based on the remotely detected physiological parameters
      (heart rate, breathing rate and heart rate variability). The accuracy of the
      model was 85% (35% greater than chance). 

PMID- 25570612
TI  - Automated health alerts from Kinect-based in-home gait measurements.
AB  - A method for automatically generating alerts to clinicians in response to changes
      in in-home gait parameters is investigated. Kinect-based gait measurement systems
      were installed in apartments in a senior living facility. The systems
      continuously monitored the walking speed, stride time, and stride length of
      apartment residents. A framework for modeling uncertainty in the residents' gait
      parameter estimates, which is critical for robust change detection, is developed;
      along with an algorithm for detecting changes that may be clinically relevant.
      Three retrospective case studies, of individuals who had their gait monitored for
      periods ranging from 12 to 29 months, are presented to illustrate use of the
      alert method. Evidence suggests that clinicians could be alerted to health
      changes at an early stage, while they are still small and interventions may be
      most successful. Additional potential uses are also discussed. 

PMID- 25570613
TI  - The use of inertial sensors for the classification of rehabilitation exercises.
AB  - The benefits of exercise in rehabilitation after orthopaedic surgery or following
      a musculoskeletal injury has been widely established. Within a hospital or
      clinical environment, adherence levels to rehabilitation exercise programs are
      high due to the supervision of the patient during the rehabilitation process.
      However, adherence levels drop significantly when patients are asked to perform
      the program at home. This paper describes the use of simple inertial sensors for
      the purpose of developing a biofeedback system to monitor adherence to
      rehabilitation programs. The results show that a single sensor can accurately
      distinguish between seven commonly prescribed rehabilitation exercises with
      accuracies between 93% and 95%. Results also show that the use of multiple sensor
      units does not significantly improve results therefore suggesting that a single
      sensor unit can be used as an input to an exercise biofeedback system. 

PMID- 25570614
TI  - Using a pilot study to establish experimental methods for inexpensive
      instrumented insoles used in dynamic skiing analysis.
AB  - Loss of balance leads to increased likelihood of falling for human locomotion.
      Determining the likelihood of falling for skiing locomotion is challenging
      because, unlike walking, normal locomotion is not clearly defined. One of the
      first learned styles of skiing is wedge style (WS). WS affords relatively easier
      balancing and speed control due to a wide base of support and greater resistance
      to forward movement, respectively. As skiers become more familiar with WS, their
      sensory, cognition, and actuation improve and they are able to apply more
      advanced styles, namely parallel style (PS), which requires refined balance. This
      paper studies the effects of WS and PS, on a single subject pilot study, and how
      they effect the likelihood of falling. A traditional laboratory setting was not
      suitable because of extreme difficulty and expense required to mimic the
      environment. Specially designed instrumented insoles were used to capture force
      data in a mountain environment. 

PMID- 25570615
TI  - Wearable static posturography solution using a novel pressure sensor sole.
AB  - Static posturography is an important measurement in the diagnostic workup for
      patients with postural instability. New wearable sensor technologies enable
      researchers to use in-shoe pressure soles in the home environment and outdoor
      applications. In this study a newly developed in-shoe pressure sole was used for
      calculating the sway path and 95% confidence ellipse area as the standard
      parameters of typical static posturography. Insole posturography was validated on
      24 subjects by a state of the art pressure plate assessment during three static
      posturography conditions (eyes open, eyes closed and barefoot). The adaptive low
      pass filtered data resulted in an overall correlation of 0.63 to 0.78 for the
      sway path and 0.66 to 0.79 for the 95% confidence ellipse area. Individual
      correlations of up to 0.97 for the sway path and 0.99 for the 95% confidence
      ellipse area could be obtained. Future applications could utilize the mobile
      advantage of in-shoe pressure soles and measure static and dynamic posturography
      in clinical and home environments.

PMID- 25570616
TI  - Quantitative assessment of multiple sclerosis using inertial sensors and the TUG
      test.
AB  - Multiple sclerosis (MS) is a progressive neurological disorder affecting between
      2 and 2.5 million people globally. Tests of mobility form part of clinical
      assessments of MS. Quantitative assessment of mobility using inertial sensors has
      the potential to provide objective, longitudinal monitoring of disease
      progression in patients with MS. The mobility of 21 patients (aged 25-59 years, 8
      M, 13 F), diagnosed with relapsing-remitting MS was assessed using the Timed up
      and Go (TUG) test, while patients wore shank-mounted inertial sensors. This
      exploratory, cross-sectional study aimed to examine the reliability of
      quantitative measures derived from inertial sensors during the TUG test, in
      patients with MS. Furthermore, we aimed to determine if disease status (as
      measured by the Multiple Sclerosis Impact Scale (MSIS-29) and the Expanded
      Disability Status Score (EDSS)) can be predicted by assessment using a TUG test
      and inertial sensors. Reliability analysis showed that 32 of 52 inertial sensors
      parameters obtained during the TUG showed excellent intrasession reliability,
      while 11 of 52 showed moderate reliability. Using the inertial sensors
      parameters, regression models of the EDSS and MSIS-29 scales were derived using
      the elastic net procedure. Using cross validation, an elastic net regularized
      regression model of MSIS yielded a mean square error (MSE) of 334.6 with 25
      degrees of freedom (DoF). Similarly, an elastic net regularized regression model
      of EDSS yielded a cross-validated MSE of 1.5 with 6 DoF. Results suggest that
      inertial sensor parameters derived from MS patients while completing the TUG test
      are reliable and may have utility in assessing disease state as measured using
      EDSS and MSIS. 

PMID- 25570617
TI  - Does external walking environment affect gait patterns?
AB  - The objective of this work is to develop an understanding of the relationship
      between mobility metrics obtained outside of the clinic or laboratory and the
      context of the external environment. Ten subjects walked with an inertial sensor
      on each shank and a wearable camera around their neck. They were taken on a
      thirty minute walk in which they mobilized over the following conditions; normal
      path, busy hallway, rough ground, blind folded and on a hill. Stride time, stride
      time variability, stance time and peak shank rotation rate during swing were
      calculated using previously published algorithms. Stride time was significantly
      different between several of the conditions. Technological advances mean that
      gait variables can now be captured as patients go about their daily lives. The
      results of this study show that the external environment has a significant impact
      on the quality of gait metrics. Thus, context of external walking environment is
      an important consideration when analyzing ambulatory gait metrics from the
      unsupervised home and community setting. 

PMID- 25570618
TI  - Detection of variations in cognitive workload using multi-modality physiological
      sensors and a large margin unbiased regression machine.
AB  - Physiological sensor based workload estimation technology provides a real-time
      means for assessing cognitive workload and has a broad range of applications in
      cognitive ergonomics, mental health monitoring, etc. In this paper we report a
      study on detecting changes in workload using multi-modality physiological sensors
      and a novel feature extraction and classification algorithm. We conducted a
      cognitive workload experiment involving multiple subjects and collected an
      extensive data set of EEG, ECG and GSR signals. We show that the GSR signal is
      consistent with the variations of cognitive workload in 75% of the samples. To
      explore cardiac patterns in ECG that are potentially correlated with the
      cognitive workload process, we computed various heart-rate-variability features.
      To extract neuronal activity patterns in EEG related to cognitive workload, we
      introduced a filter bank common spatial pattern filtering technique. As there can
      be large variations in e.g. individual responses to the cognitive workload, we
      propose a large margin unbiased recursive feature extraction and regression
      method. Our leave-one-subject-out cross validation test shows that, using the
      proposed method, EEG can provide significantly better prediction of the cognitive
      workload variation than ECG, with 87.5% vs 62.5% in accuracy rate. 

PMID- 25570619
TI  - ERP signal estimation from single trial EEG.
AB  - Non-invasive EEG recordings are subject to effects such as surface conduction,
      resulting in very low signal to noise ratio (SNR). The conventional approach of
      using signal averaging to improve the SNR cannot be used for single trial EEG
      estimation. As such, this paper proposes a beamforming based technique that can
      be used to improve the signal quality from a signal trial EEG measurement.
      Results on experimental data show that the proposed technique can successfully
      isolate the signal of interest from background processes. 

PMID- 25570620
TI  - Cognitive workload estimation due to vague visual stimuli using saccadic eye
      movements.
AB  - Visual perception is affected by the quality of stimulus. In this paper, we
      investigate the rise in cognitive workload of an individual performing visual
      task due to vague visual stimuli. We make use of normalized average peak saccadic
      velocity to estimate the cognitive workload. Results obtained from 16 human
      subjects show that the mean of peak saccadic velocity increases with workload
      indicating that faster saccades are required to obtain information as the
      workload increases. This technique should find application in assessment of
      vigilance and cognitive performance in many demanding professional, industrial
      and transportation situation. 

PMID- 25570621
TI  - Joint optimization of algorithmic suites for EEG analysis.
AB  - Electroencephalogram (EEG) data analysis algorithms consist of multiple
      processing steps each with a number of free parameters. A joint optimization
      methodology can be used as a wrapper to fine-tune these parameters for the
      patient or application. This approach is inspired by deep learning neural network
      models, but differs because the processing layers for EEG are heterogeneous with
      different approaches used for processing space and time. Nonetheless, we treat
      the processing stages as a neural network and apply backpropagation to jointly
      optimize the parameters. This approach outperforms previous results on the BCI
      Competition II - dataset IV; additionally, it outperforms the common spatial
      patterns (CSP) algorithm on the BCI Competition III dataset IV. In addition, the
      optimized parameters in the architecture are still interpretable. 

PMID- 25570622
TI  - Towards a multimodal bioelectrical framework for the online mental workload
      evaluation.
AB  - In this study, a framework able to classify online different levels of mental
      workload induced during a simulated flight by using the combination of the
      Electroencephalogram (EEG) and the Heart Rate (HR) biosignals has been proposed.
      Ten healthy subjects were involved in the experimental protocol, performing the
      NASA - Multi Attribute Task Battery (MATB) over three different difficulty levels
      in order to simulate three classic showcases in a flight scene (cruise flight
      phase, flight level maintaining, and emergencies). The analyses showed that the
      proposed system is able to estimate online the mental workload of the subjects
      over the three different conditions reaching a high discriminability (p<.05). In
      addition, it has been found that the classification parameters remained stable
      within a week, without recalibrating the system with new parameters.

PMID- 25570623
TI  - A neurophysiological training evaluation metric for air traffic management.
AB  - The aim of this work was to analyze the possibility to apply a neuroelectrical
      cognitive metrics for the evaluation of the training level of subjects during the
      learning of a task employed by Air Traffic Controllers (ATCos). In particular,
      the Electroencephalogram (EEG), the Electrocardiogram (ECG) and the
      Electrooculogram (EOG) signals were gathered from a group of students during the
      execution of an Air Traffic Management (ATM) task, proposed at three different
      levels of difficulty. The neuroelectrical results were compared with the
      subjective perception of the task difficulty obtained by the NASA-TLX
      questionnaires. From these analyses, we suggest that the integration of
      information derived from the power spectral density (PSD) of the EEG signals, the
      heart rate (HR) and the eye-blink rate (EBR) return important quantitative
      information about the training level of the subjects. In particular, by focusing
      the analysis on the direct and inverse correlation of the frontal PSD theta (4-7
      (Hz)) and HR, and of the parietal PSD alpha (10-12 (Hz)) and EBR, respectively,
      with the degree of mental and emotive engagement, it is possible to obtain useful
      information about the training improvement across the training sessions. 

PMID- 25570624
TI  - Towards kinematic modeling of a multi-DOF tendon driven robotic catheter.
AB  - This paper presents a recent study on kinematic modeling of a remote-controlled
      active catheter. The tip steering motion of the catheter is actuated in a tendon
      driven manner. Two antagonistic groups of tendon actuation realize the distal tip
      deflecting with two-degree-of-freedom (2-DOF) allowing it to reach a considerable
      large spatial workspace without catheter shaft rotation. However, when modeling
      such bending deformation, the sequential rotation approach is easily misapplied.
      We address this problem and introduce a novel and unified modeling methodology
      based on the concept of simultaneous rotation and the use of Rodrigues' rotation
      formula. An accurate model is created for robotic catheters and also can be
      generalized to common multi-tendon-driven continuum manipulators. It is essential
      in achieving accurate control and improving autonomous execution of command
      tracking tasks. 

PMID- 25570625
TI  - Simulation of motor current waveform as an index for aortic valve open-close
      condition during ventricular support.
AB  - Monitoring of aortic valve (AV) opening and closure during heart pump support by
      a left ventricular assist device (LVAD) is crucial in preventing adverse events
      such as thrombus formation near the AV. In preventing adverse events such as
      thrombus formation near the AV. In this paper, simulations of LVAD motor current
      waveform were undertaken to evaluate its suitability for ascertaining aortic
      valve status. A two-dimensional fluid-structure interaction finite-element model
      is presented to predict AV closure during LVAD outflow, useful in the development
      of a pump speed controller. 

PMID- 25570626
TI  - Numerical investigation of the electrical current effect on the fibrous tissue
      growth around biomaterials.
AB  - The objective of this study is to assess numerically the effect of applying
      electrical current on the fibrous tissue growth around polyethylene disk-shaped
      implants while subcutaneously placed inside 60 day old male Han-Wistar rats. This
      problem can be formulated as a design problem where the goal is to determine the
      parameters of a partial differential operator to achieve a desired effect. These
      electrical current parameters are computed using a regularized iterative method.
      The obtained results reveal that employing an appropriate electrical current
      profile can reduce the fibrous tissue concentration around the considered implant
      by up to 80%. This preliminary study tends to demonstrate the effectiveness of
      this novel and non-invasive approach to shield the implant from intolerable
      levels of fibrous tissue growth, which consequently expands the lifespan and
      functionality of implanted devices, as well as avoids costly and traumatic
      surgical procedures. 

PMID- 25570627
TI  - A multi-scale feedback control system model for wound healing electrical
      activity: therapeutic device/protocol implications.
AB  - Regulation, growth and healing in biological systems involve many interconnected
      and interdependent processes that include chemical and electrical mechanisms of
      action. Unfortunately, the significant contributions that electrical events
      provide are often overlooked; resulting in a poor transfer of knowledge from
      science, to engineering and finally to therapy. Wound site electrical processes
      can influence cell migration, fluid transport, cellular signaling events, gene
      expression, cell differentiation and cell proliferation; affecting both form and
      function at the cell, tissue and organ levels. Wound healing, and its
      interrelationships with transport, regeneration, and growth, cannot be understood
      or therapeutically assisted unless both chemical and electrical activities
      associated with the healing process are addressed. 

PMID- 25570628
TI  - Neutron activation processes simulation in an Elekta medical linear accelerator
      head.
AB  - Monte Carlo estimation of the giant-dipole-resonance (GRN) photoneutrons inside
      the Elekta Precise LINAC head (emitting a 15 MV photon beam) were performed using
      the MCNP6 (general-purpose Monte Carlo N-Particle code, version 6). Each
      component of LINAC head geometry and materials were modelled in detail using the
      given manufacturer information. Primary photons generate photoneutrons and its
      transport across the treatment head was simulated, including the (n, gamma)
      reactions which undergo activation products. The MCNP6 was used to develop a
      method for quantifying the activation of accelerator components. The approach
      described in this paper is useful in quantifying the origin and the amount of
      nuclear activation. 

PMID- 25570629
TI  - Multiobjective optimization-based design of wearable electrocardiogram monitoring
      systems.
AB  - Nowadays, the use of Wearable User Interfaces has been extensively growing in
      medical monitoring applications. However, production and manufacture of
      prototypes without automation tools may lead to non viable results since it is
      often common to find an optimization problem where several variables are in
      conflict with each other. Thus, it is necessary to design a strategy for
      balancing the variables and constraints, systematizing the design in order to
      reduce the risks that are present when it is exclusively guided by the intuition
      of the developer. This paper proposes a framework for designing wearable ECG
      monitoring systems using multi-objective optimization. The main contributions of
      this work are the model to automate the design process, including a mathematical
      expression relating the principal variables that make up the criteria of
      functionality and wearability. We also introduce a novel yardstick for deciding
      the location of electrodes, based on reducing interference from ECG by maximizing
      the electrode-skin contact. 

PMID- 25570630
TI  - Latent state-space models for neural decoding.
AB  - Ensembles of single-neurons in motor cortex can show strong low-dimensional
      collective dynamics. In this study, we explore an approach where neural decoding
      is applied to estimated low-dimensional dynamics instead of to the full recorded
      neuronal population. A latent state-space model (SSM) approach is used to
      estimate the low-dimensional neural dynamics from the measured spiking activity
      in population of neurons. A second state-space model representation is then used
      to decode kinematics, via a Kalman filter, from the estimated low-dimensional
      dynamics. The latent SSM-based decoding approach is illustrated on neuronal
      activity recorded from primary motor cortex in a monkey performing naturalistic 3
      D reach and grasp movements. Our analysis show that 3-D reach decoding
      performance based on estimated low-dimensional dynamics is comparable to the
      decoding performance based on the full recorded neuronal population. 

PMID- 25570631
TI  - Enhancing detection of steady-state visual evoked potentials using individual
      training data.
AB  - Although the performance of steady-state visual evoked potential (SSVEP)-based
      brain-computer interfaces (BCIs) has improved gradually in the past decades, it
      still does not meet the requirement of a high communication speed in many
      applications. A major challenge is the interference of spontaneous background EEG
      activities in discriminating SSVEPs. An SSVEP BCI using frequency coding
      typically does not have a calibration procedure since the frequency of SSVEPs can
      be recognized by power spectrum density analysis (PSDA). However, the detection
      rate can be deteriorated by the spontaneous EEG activities within the same
      frequency range because phase information of SSVEPs is ignored in frequency
      detection. To address this problem, this study proposed to incorporate individual
      SSVEP training data into canonical correlation analysis (CCA) to improve the
      frequency detection of SSVEPs. An eight-class SSVEP dataset recorded from 10
      subjects in a simulated online BCI experiment was used for performance
      evaluation. Compared to the standard CCA method, the proposed method obtained
      significantly improved detection accuracy (95.2% vs. 88.4%, p<0.05) and
      information transfer rates (ITR) (104.6 bits/min vs. 89.1 bits/min, p<0.05). The
      results suggest that the employment of individual SSVEP training data can
      significantly improve the detection rate and thereby facilitate the
      implementation of a high-speed BCI.

PMID- 25570632
TI  - Hybrid decoding of both spikes and low-frequency local field potentials for brain
      machine interfaces.
AB  - The best-performing brain-machine interfaces (BMIs) to date decode movement
      intention from intracortically recorded spikes, but these signals may be lost
      over time. A way to increase the useful lifespan of BMIs is to make more
      comprehensive use of available neural signals. Recent studies have demonstrated
      that the local field potential (LFP), a potentially more robust signal, can also
      be used to control a BMI. However, LFP-driven performance has fallen short of the
      best spikes-driven performance. Here we report a biomimetic BMI driven by low
      frequency LFP that enabled a rhesus monkey to acquire and hold randomly placed
      targets with 99% success rate. Although LFP-driven performance was still worse
      than when decoding spikes, to the best of our knowledge this represents the
      highest-performing LFP-based BMI. We also demonstrate a new hybrid BMI that
      decodes cursor velocity using both spikes and LFP. This hybrid decoder improved
      performance over spikes-only decoding. Our results suggest that LFP can
      complement spikes when spikes are available or provide an alternative control
      signal if spikes are absent. 

PMID- 25570633
TI  - Relationship between microelectrode array impedance and chronic recording quality
      of single units and local field potentials.
AB  - Practical application of intracortical microelectrode technology is currently
      hindered by the inability to reliably record neuronal signals chronically. The
      precise mechanism of device failure is still under debate, but most likely
      includes some combination of tissue reaction, mechanical failure, and chronic
      material degradation. Impedance is a measure of the ease with which current flows
      through a working electrode under a driving voltage. Impedance has been
      hypothesized to provide information about an electrode's surrounding tissue
      reaction as well as chronic insulation degradation. In this study, we
      investigated the relationship between an electrode's impedance and its chronic
      recording performance as measured by the number of isolatable single units and
      the quality of local field potential recordings. Two 64-channel electrode arrays
      implanted in separate monkeys were assessed. We found no simple relationship
      between impedance and recording quality that held for both animals across all
      time periods. This suggests that future investigations on the topic should adopt
      a more fine-grained within-day and within-animal analysis. We also found new
      evidence from local field potential spatial correlation supporting the theory
      that insulation degradation is an important contributor to electrode failure. 

PMID- 25570634
TI  - On the asynchronously continuous control of mobile robot movement by motor
      cortical spiking activity.
AB  - This paper presents an asynchronously intracortical brain-computer interface
      (BCI) which allows the subject to continuously drive a mobile robot. This system
      has a great implication for disabled patients to move around. By carefully
      designing a multiclass support vector machine (SVM), the subject's self-paced
      instantaneous movement intents are continuously decoded to control the mobile
      robot. In particular, we studied the stability of the neural representation of
      the movement directions. Experimental results on the nonhuman primate showed that
      the overt movement directions were stably represented in ensemble of recorded
      units, and our SVM classifier could successfully decode such movements
      continuously along the desired movement path. However, the neural representation
      of the stop state for the self-paced control was not stably represented and could
      drift. 

PMID- 25570635
TI  - Enhancing unsupervised canonical correlation analysis-based frequency detection
      of SSVEPs by incorporating background EEG.
AB  - Steady-state visual evoked potential (SSVEP)-based brain-computer interfaces
      (BCIs) have potential to provide a fast communication channel between human brain
      and external devices. In SSVEP-based BCIs, Canonical Correlation Analysis (CCA)
      has been widely used to detect frequency-coded SSVEPs due to its high efficiency
      and robustness. However, the detectability of SSVEPs differs among frequencies
      due to a power-law distribution of the power spectra of spontaneous
      electroencephalogram (EEG) signals. This study proposed a new method based on the
      fact that changes of canonical correlation coefficients for SSVEPs and background
      EEG signals follow the same trend along frequency. The proposed method defined a
      normalized canonical correlation coefficient, the ratio of the canonical
      correlation coefficient for SSVEPs to the mean of the canonical correlation
      coefficients for background EEG signals, to enhance the frequency detection of
      SSVEPs. An SSVEP dataset from 13 subjects was used for comparing classification
      performance between the proposed method and the standard CCA method.
      Classification accuracy and simulated information transfer rates (ITR) suggest
      that, in an unsupervised way, the proposed method could considerably improve the
      frequency detection accuracy of SSVEPs with little computational effort. 

PMID- 25570636
TI  - Test of a customized compliant ankle rehabilitation device in unpowered mode.
AB  - Presented is the design, implementation, and initial gait testing of a
      lightweight, compliant robotic device for ankle rehabilitation. Many patients
      with neuromuscular disorders suffer deficits in sensorimotor control of the ankle
      joint, leading to an abnormal walking pattern. Robotic devices have been used to
      assist ankle rehabilitation. However, these devices are usually heavy and rigid,
      which can deviate a natural gait pattern. To address these issues, our team has
      developed a light weight, compliant ankle robotic device actuated by artificial
      pneumatic muscles. A total of 3 healthy subjects were recruited to test whether
      the mechanical structure of the device deviates gait. We used a 3-dimensional
      (3D) motion analysis system to record and analyze subjects' ankle kinematics
      during gait while walking barefoot and while wearing the device unpowered. The
      preliminary results suggest that the device caused some, but minimal changes in
      ankle kinematics during gait. The changes were mainly caused by the device's
      rigid footplate, used to support the foot and connect to the pneumatic muscles.
      The preliminary results will be used for future improvement of the device. 

PMID- 25570637
TI  - Preliminary investigation of effects of a quasi-passive knee exoskeleton on gait
      energetics.
AB  - In this paper, we explain that the human knee behavior in the weight acceptance
      phase of gait (first ~40% of gait cycle) resembles that of a linear torsional
      spring. This led us to study the effects of the assistance provided by a pair of
      quasi-passive knee exoskeletons, which implement springs in parallel with the
      knee joints in the weight acceptance phase. Using the exoskeletons in a series of
      experiments on seven participants, we found that the exoskeleton mildly but non
      significantly reduces the metabolic power of walking. We also found that the
      metabolic power of walking is significantly correlated with both the positive
      rate of moment generation and positive mechanical power of the lower extremity
      joints. This suggests that augmenting exoskeletons can aim to reduce both the
      muscle force and work generation to reduce the metabolic cost of walking.

PMID- 25570638
TI  - Autonomous exoskeleton reduces metabolic cost of walking.
AB  - We developed an autonomous powered leg exoskeleton capable of providing large
      amounts of positive mechanical power to the wearer during powered plantarflexion
      phase of walking. The autonomous exoskeleton consisted of a winch actuator fasted
      to the shin which pulled on fiberglass struts attached to a boot. The fiberglass
      struts formed a rigid extension of the foot when the proximal end of the strut
      was pulled in forward by the winch actuator. This lightweight, geometric
      transmission allowed the electric winch actuator to efficiently produce
      biological levels of power at the ankle joint. The exoskeleton was powered and
      controlled by lithium polymer batteries and motor controller worn around the
      waist. Preliminary testing on two subjects walking at 1.4 m/s resulted in the
      exoskeleton reducing the metabolic cost of walking by 6-11% as compared to not
      wearing the device. The exoskeleton provided a peak mechanical power of over 180
      W at each ankle (mean standard +/- deviation) and an average positive mechanical
      power of 27 +/- 1 W total to both ankles, while electrically using 75-89 W of
      electricity. The batteries (800 g) used in this experiment are estimated to be
      capable of providing this level of assistance for up to 7 km of walking. 

PMID- 25570639
TI  - A modular low-clearance wrist orthosis for improving wrist motion in children
      with cerebral palsy.
AB  - Children with Cerebral Palsy (CP) often exhibit impairments in the coordination
      of the grip and lift phases of arm movements that directly impact their ability
      to perform activities of daily living (ADLs). The application of assistive
      robotic therapy to children with spastic hemiplegic CP has shown that augmented
      movement training can lead to improved functional outcomes and improved arm
      kinematics. Assistive robotic therapy of the wrist has been shown to help improve
      motor skills in stroke patients, but the devices employed are often large and
      obtrusive, focusing on a repeated motion rather than a task-based itinerary.
      Here, we propose a lightweight low clearance wrist orthosis for use in children
      with Cerebral Palsy that actuates pronation/supination and flexion/extension of
      the wrist. 

PMID- 25570641
TI  - Development of an assist controller with robot suit HAL for hemiplegic patients
      using motion data on the unaffected side.
AB  - Among several characteristics seen in gait of hemiplegic patients after stroke,
      symmetry is known to be an indicator of the degree of impairment of walking
      ability. This paper proposes a control method for a wearable type lower limb
      motion assist robot to realize spontaneous symmetric gait for these individuals.
      This control method stores the motion of the unaffected limb during swing and
      then provides motion support on the affected limb during the subsequent swing
      using the stored pattern to realize symmetric gait based on spontaneous limb
      swing. This method is implemented on the robot suit HAL (Hybrid Assistive Limbs).
      Clinical tests were conducted in order to assess the feasibility of the control
      method. Our case study involved participation of one chronic stroke patient who
      was not able to flex his right knee. As a result, the walking support for
      hemiplegic leg provided by the HAL improved the subject's gait symmetry. The
      feasibility study showed promising basis for the future clinical study. 

PMID- 25570640
TI  - Muscular activity when walking in a non-anthropomorphic wearable robot.
AB  - Wearable robots should be designed not to alter human physiological motion.
      Perturbations introduced by a robot can be quantified by measuring EMG activity.
      This paper presents tests on the LENAR, an intrinsically back-drivable non
      anthropomorphic lower limb wearable robot designed to provide hip and knee
      flexion/extension assistance. In previous works the robot was demonstrated to
      exhibit low mechanical impedance and to introduce minor alterations to human
      kinematic patterns during walking. In this paper muscular activity is assessed,
      demonstrating small alterations in the EMG patterns during the interaction with
      the robot, in both unpowered and assistive mode. 

PMID- 25570643
TI  - Passive reach and grasp with functional electrical stimulation and robotic arm
      support.
AB  - Rehabilitation of arm and hand function is crucial to increase functional
      independence of stroke subjects. Here, we investigate the technical feasibility
      of an integrated training system combining robotics and functional electrical
      stimulation (FES) to support reach and grasp during functional manipulation of
      objects. To support grasp and release, FES controlled the thumb and fingers using
      Model Predictive Control (MPC), while a novel 3D robotic manipulator provided
      reach support. The system's performance was assessed in both stroke and
      blindfolded healthy subjects, where the subject's passive arm and hand made
      functional reach, grasp, move and release movements while manipulating objects.
      The success rate of complete grasp, move and release tasks with different objects
      ranged from 33% to 87% in healthy subjects. In severe chronic stroke subjects
      especially the hand opening had a low success rate (<25%) and no complete
      movements could be made. We demonstrated that our developed integrated training
      system can move the passive arm and hand for functional pick and place movements.
      In the current setup, the positioning accuracy of the robot with respect to the
      object position was critical for the overall performance. The use of a higher
      virtual stiffness and including feedback of object position in the robot control
      would likely improve the relative position accuracy. The system has potential for
      post-stroke rehabilitation, where support could be reduced based on patient
      performance which is needed to aid motor relearning of reach, grasp and release.

PMID- 25570642
TI  - Low-power polling mode of the next-generation IMES2 implantable wireless EMG
      sensor.
AB  - The IMES1 Implantable MyoElectric Sensor device is currently in human clinical
      trials led by the Alfred Mann Foundation. The IMES is implanted in a residual
      limb and is powered wirelessly using a magnetic field. EMG signals resulting from
      the amputee's voluntary movement are amplified and transmitted wirelessly by the
      IMES to an external controller which controls movement of an external motorized
      prosthesis. Development of the IMES technology is on-going, producing the next
      generation IMES2. Among various improvements, a new feature of the IMES2 is a low
      power polling mode. In this low-power mode, the IMES2 power consumption can be
      dramatically reduced when the limb is inactive through the use of a polled
      sampling. With the onset of EMG activity, the IMES2 system can switch to the
      normal higher sample rate to allow the acquisition of high-fidelity EMG data for
      prosthesis control. 

PMID- 25570644
TI  - A strategy for labeling data for the neural adaptation of a powered lower limb
      prosthesis.
AB  - Pattern recognition algorithms that use EMG signals have been proposed to help
      control powered lower limb prostheses. These algorithms do not automatically
      compensate for disturbances in EMG signals, resulting in deterioration of
      algorithm accuracies. Supervised adaptive pattern recognition algorithms can
      solve this problem, but require correct labeling of new data. Information from
      embedded mechanical sensors can be compared to the characteristic gait profiles
      of the different modes to identify the mode of the user's most recent stride and
      provide a label for new data. The purpose of this study was to develop a gait
      pattern estimator (GPE) that could automatically make such a comparison. The GPE
      output was used to supervise an adaptive EMG-based pattern recognition algorithm.
      Our results indicate that using GPE-based adaptation helped prevent
      classification errors that would otherwise occur between experimental sessions.
      The GPE could accurately label new data with a low error rate of approx. 2%. The
      low error rate of the GPE was reflected in the accuracy of an adapted pattern
      recognition algorithm. The error rate of the adapted algorithm that was
      supervised by the GPE was not significantly different from one that used perfect
      supervision. 

PMID- 25570645
TI  - Delineating the effects of anodal transcranial direct current stimulation on
      myoelectric control based on slow cortical potentials.
AB  - Active cortical participation in rehabilitation procedures may be facilitated by
      modulating neuromuscular electrical stimulation (NMES) with electromyogram (EMG)
      and electroencephalogram (EEG) derived biopotentials, that represent simultaneous
      volitional effort. Here, the ability of the nervous system to respond to
      intrinsic or extrinsic stimuli by reorganizing its structure, function, and
      connections is called neuroplasticity. Neuroplasticity is involved in post-stroke
      functional disturbances, but also in rehabilitation. Beneficial neuroplastic
      changes may be facilitated with an adjuvant treatment with non-invasive brain
      stimulation (NIBS). This paper presents the results from a motor cortex anodal
      tDCS-EEG/EMG study in healthy volunteers. We investigated slow cortical
      potentials (SCP) during self-initiated movements. In this preliminary study, we
      found that anodal tDCS increased baseline-normalized post-tDCS mean power in the
      Theta band (4-8 Hz) of resting state EEG (60.71% vs. 8.36%; p<0.01), and
      decreased the slope of post-tDCS SCP from motor task-related EEG (-6.43 au/sec
      vs. -4.86 au/sec; p=0.021) when compared to sham tDCS. These preliminary results
      are discussed based on an accumulator model for spontaneous neural activity which
      postulates that a decision threshold applied to auto-correlated noise-in this
      case the output of a leaky stochastic accumulator-can account for the specific
      shape of the SCP prior to movement. We postulate that the anodal tDCS facilitated
      change in the slope of SCP may be related to the reaction times during a cued
      movement task since our prior work showed that anodal tDCS decreases the delay in
      initiation of muscle contraction and increases the delay in termination of muscle
      activity.

PMID- 25570646
TI  - Functional electrical stimulation based on a pelvis support robot for gait
      rehabilitation of hemiplegic patients after stroke.
AB  - More and more stroke survivors are suffering from physical motor impairments.
      Current therapeutic interventions have various limits to the efficient recovery
      of normal motor function of the lower limbs. Therefore, we propose a novel gait
      rehabilitation system for hemiplegic patients after stroke. It integrates
      functional electrical stimulation (FES) with a pelvis-supporting robotic system.
      A corresponding relationship between the gait phase and the active lateral
      movement of the pelvis is first constructed from experiments on simulated
      hemiplegic patients. By estimating the gait phase from the lateral motion of the
      pelvis based on this relationship, the timing of FES sent to the muscles of the
      lower limbs can be automatically determined during a gait cycle. After
      experiments on simulated hemiplegic stroke survivors with the FES control
      algorithm, the proposed algorithm and the gait rehabilitation system are verified
      to be feasible and promising. 

PMID- 25570647
TI  - A scalable FPGA-based cerebellum for passage-of-time representation.
AB  - The cerebellum plays a critical role for sensorimotor control and learning.
      However dysmertria or delays in movements' onsets consequent to damages in
      cerebellum cannot be cured completely at the moment. To foster a potential cure
      based on neuroprosthetic technology, we present a frame-based Network-on-Chip
      (NoC) hardware architecture for implementing a bio-realistic cerebellum model
      with 100,000 neurons, which has been used for studying timing control or passage
      of-time (POT) encoding mediated by the cerebellum. The results demonstrate that
      our implementation can reproduce the POT functionality properly. The
      computational speed can achieve to 25.6 ms for simulating 1 sec real world
      activities. Furthermore, we show a hardware electronic setup and illustrate how
      the silicon cerebellum can be adapted as a potential neuroprosthetic platform for
      future biological or clinical applications. 

PMID- 25570648
TI  - Tissue thickness estimation for high precision head-tracking using a
      galvanometric laser scanner - a case study.
AB  - Marker-less optical head-tracking constitutes a comfortable alternative with no
      exposure to radiation for realtime monitoring in radiation therapy. Supporting
      information such as tissue thickness has the potential to improve spatial
      tracking accuracy. Here we study how accurate tissue thickness can be estimated
      from the near-infrared (NIR) backscatter obtained from laser scans. In a case
      study, optical data was recorded with a galvanometric laser scanner from three
      subjects. A tissue ground truth from MRI was robustly matched via customized bite
      blocks. We show that Gaussian Processes accurately model the relationship between
      NIR features and tissue thickness. They were able to predict the tissue thickness
      with less than 0.5 mm root mean square error. Individual scaling factors for all
      features and an additional incident angle feature had positive effects on this
      performance. 

PMID- 25570650
TI  - Detection of urinary tract infections on lab-on-chip device by measuring photons
      emitted from ATP bioluminescence.
AB  - A microfluidic Lab-on-chip (LOC) platform for in vitro detecting Urinary Tract
      Infections (UTI) for clinical diagnostic applications has been built. Based on
      one commercial adenosine 5'-triphosphate (ATP) assay kit, one chip designed
      before was applied to detect UTI with the help of photomultiplier tube (PMT) and
      quantitative determination was made by measuring the photons of light emitted in
      the bioluminescent reaction of ATP with the enzyme luciferase. The chip had been
      tested and materials had been well prepared before testing the PMT detecting
      system. The data from PMT were visualized by the LabviewTM, appearing good
      linearity between voltage values and the concentration of the ATP ranging from
      2*10(-12) M to 2*10(-8) M. Fresh urine sample with different amounts of
      Escherichia coli had been measured by the system, appearing good linearity trend
      between the voltage values and number of the E.coli. This study successfully
      expressed the concept of measuring ATP directly in the urine to quickly and
      accurately detect UTI on a microfluidic chip. 

PMID- 25570649
TI  - An integrated evaluation for the performance of clinical engineering department.
AB  - Performance benchmarking have become a very important component in all successful
      organizations nowadays that must be used by Clinical Engineering Department (CED)
      in hospitals. Many researchers identified essential mainstream performance
      indicators needed to improve the CED's performance. These studies revealed
      mainstream performance indicators that use the database of a CED to evaluate its
      performance. In this work, we believe that those indicators are insufficient for
      hospitals. Additional important indicators should be included to improve the
      evaluation accuracy. Therefore, we added new indicators: technical/maintenance
      indicators, economic indicators, intrinsic criticality indicators, basic hospital
      indicators, equipment acquisition, and safety indicators. Data is collected from
      10 hospitals that cover different types of healthcare organizations. We developed
      a software tool that analyses collected data to provide a score for each CED
      under evaluation. Our results indicate that there is an average gap of 67%
      between the CEDs' performance and the ideal target. The reasons for the
      noncompliance are discussed in order to improve performance of CEDs under
      evaluation.

PMID- 25570651
TI  - A novel device to preserve intestinal tissue ex-vivo by cold peristaltic
      perfusion.
AB  - In the past two decades, much advancement has been made in the area of organ
      procurement and preservation for the transplant of kidneys, livers, and lungs.
      However, small intestine preservation remains unchanged. We propose a new
      preservation system for intestinal grafts that has the potential to increase the
      viability of the organ during transport. When experimented with porcine
      intestine, our device resulted in superior tissue quality than tissue in standard
      of care. 

PMID- 25570652
TI  - Towards a fluoroscopic cancer screening capsule for the small intestine.
AB  - Efficient microcancer detection in the small intestine can be realised by
      infrared fluorescence endoscopy (IRFE). The affected areas can be visualised
      through that technique in conjunction with an infrared fluorescent-labeling
      contrast agent, which is selectively uptaken by cancerous cells. In this paper we
      present a screening capsule prototype that is able to measure IR fluorescence
      levels emitted by fluorophore indocyanine green (ICG) of different
      concentrations. The mixed-signal system presented has small area footprint, and
      very little power requirements. In-vitro experiments have shown that the system
      is able to detect and discriminate low concentrations of ICG in the micromolar
      region, which is required to detect early cancer in the small intestine.

PMID- 25570654
TI  - Characterization of simple wireless neurostimulators and sensors.
AB  - A single diode with a wireless power source and electrodes can act as an
      implantable stimulator or sensor. We have built such devices using RF and
      ultrasound power coupling. These simple devices could drastically reduce the
      size, weight, and cost of implants for applications where efficiency is not
      critical. However, a shortcoming has been a lack of control: any movement of the
      external power source would change the power coupling, thereby changing the
      stimulation current or modulating the sensor response. To correct for changes in
      power and signal coupling, we propose to use harmonic signals from the device.
      The diode acts as a frequency multiplier, and the harmonics it emits contain
      information about the drive level and bias. A simplified model suggests that
      estimation of power, electrode bias, and electrode resistance is possible from
      information contained in radiated harmonics even in the presence of significant
      noise. We also built a simple RF-powered stimulator with an onboard voltage
      limiter. 

PMID- 25570653
TI  - Parkinson's disease assessment based on gait analysis using an innovative RGB-D
      camera system.
AB  - Movement-related diseases, such as Parkinson's disease (PD), progressively affect
      the motor function, many times leading to severe motor impairment and dramatic
      loss of the patients' quality of life. Human motion analysis techniques can be
      very useful to support clinical assessment of this type of diseases. In this
      contribution, we present a RGB-D camera (Microsoft Kinect) system and its
      evaluation for PD assessment. Based on skeleton data extracted from the gait of
      three PD patients treated with deep brain stimulation and three control subjects,
      several gait parameters were computed and analyzed, with the aim of
      discriminating between non-PD and PD subjects, as well as between two PD states
      (stimulator ON and OFF). We verified that among the several quantitative gait
      parameters, the variance of the center shoulder velocity presented the highest
      discriminative power to distinguish between non-PD, PD ON and PD OFF states (p =
      0.004). Furthermore, we have shown that our low-cost portable system can be
      easily mounted in any hospital environment for evaluating patients' gait. These
      results demonstrate the potential of using a RGB-D camera as a PD assessment
      tool. 

PMID- 25570655
TI  - A dual slope charge sampling analog front-end for a wireless neural recording
      system.
AB  - This paper presents a novel dual slope charge sampling (DSCS) analog front-end
      (AFE) architecture, which amplifies neural signals by taking advantage of the
      charge sampling concept for analog signal conditioning, such as amplification and
      filtering. The presented DSCS-AFE achieves amplification, filtering, and sampling
      in a simultaneous fashion, while consuming very small amount of power. The output
      of the DSCS-AFE produces a pulse width modulated (PWM) signal that is
      proportional to the input voltage amplitude. A circular shift register (CSR)
      utilizes time division multiplexing (TDM) of the PWM pulses to create a pseudo
      digital TDM-PWM signal that can feed a wireless transmitter. The 8-channel system
      on-a-chip was fabricated in a 0.35-MUm CMOS process, occupying 2.4 * 2.1 mm(2)
      and consuming 255 MUW from a 1.8V supply. Measured input-referred noise for the
      entire system, including the FPGA in order to recover PWM signal is 6.50 MUV(rms)
      in the 288 Hz~10 kHz range. For each channel, sampling rate is 31.25 kHz, and
      power consumption is 31.8 MUW.

PMID- 25570656
TI  - A low-cost, open-source, wireless electrophysiology system.
AB  - Many experiments in neuroscience require or would benefit tremendously from a
      wireless neural recording system. However, commercially available wireless
      systems are expensive, have moderate to high noise and are often not
      customizable. Academic wireless systems present impressive capabilities, but are
      not available for other labs to use. To overcome these limitations, we have
      developed an ultra-low noise 8 channel wireless electrophysiological data
      acquisition system using standard, commercially available components. The system
      is capable of recording many types of neurological signals, including EEG, ECoG,
      LFP and unit activity. With a diameter of just 25 mm and height of 9 mm,
      including a CR2032 Lithium coin cell battery, it is designed to fit into a small
      recording chamber while minimizing the overall implant height (Fig. 1 and 3).
      Using widely available parts we were able to keep the material cost of our system
      under $100 dollars. The complete design, including schematic, PCB layout, bill of
      materials and source code, will be released through an open source license,
      allowing other labs to modify the design to fit their needs. We have also
      developed a driver to acquire data using the BCI2000 software system. Feedback
      from the community will allow us to improve the design and create a more useful
      neuroscience research tool.

PMID- 25570657
TI  - Solar powered wrist worn acquisition system for continuous photoplethysmogram
      monitoring.
AB  - We present a solar-powered, wireless, wrist-worn platform for continuous
      monitoring of physiological and environmental parameters during the activities of
      daily life. In this study, we demonstrate the capability to produce
      photoplethysmogram (PPG) signals using this platform. To adhere to a low power
      budget for solar-powering, a 574 nm green light source is used where the PPG from
      the radial artery would be obtained with minimal signal conditioning. The system
      incorporates two monocrystalline solar cells to charge the onboard 20 mAh lithium
      polymer battery. Bluetooth Low Energy (BLE) is used to tether the device to a
      smartphone that makes the phone an access point to a dedicated server for long
      term continuous storage of data. Two power management schemes have been proposed
      depending on the availability of solar energy. In low light situations, if the
      battery is low, the device obtains a 5-second PPG waveform every minute to
      consume an average power of 0.57 mW. In scenarios where the battery is at a
      sustainable voltage, the device is set to enter its normal 30 Hz acquisition
      mode, consuming around 13.7 mW. We also present our efforts towards improving the
      charge storage capacity of our on-board super-capacitor.

PMID- 25570658
TI  - Modeling the effects of biological tissue on RF propagation from a wrist-worn
      device.
AB  - Many wireless devices in common use today are worn either on or in close
      proximity to the body. Among them are a growing number of wrist-mounted devices
      designed for applications such as activity or vital-signs monitoring, typically
      using Bluetooth technology to communicate with external devices. Here, we use a
      tissue-mimicking phantom material in conjunction with anechoic chamber and
      network analyzer testing to investigate how antenna propagation patterns in one
      such device are influenced by the electrical properties of the human wrist. A
      microstrip antenna module is mounted onto phantom material of various geometries,
      and the resulting voltage standing wave ratio (VSWR), input impedance, and
      azimuth radiation pattern are recorded in both free space and real-world
      environments. The results of this study demonstrate how the high permittivity
      values of human tissue (epsilon(r) ~ 16) affect the design parameters of
      microstrip antennas. A simulation environment using Sonnet EM software was used
      to further analyze the high dielectric effects of biological tissue on RF
      propagation.

PMID- 25570659
TI  - Single chip interrogation system for a smart shoe wireless transponder.
AB  - The objective of this paper is to design a wireless transponder for antenna-based
      sensors that can be used to simultaneously measure shear and pressure forces for
      diabetic foot diagnosis. The transponder will be placed on the top surface of a
      shoe and consists of sensor antennas and an identification system that transmits
      information to a receiver by modulating the signal reflected by the antennas
      sensor in the insole. The identification system includes an energy harvester, a
      crystal oscillator and a passive mixer. A single chip interrogation circuit has
      been designed in IBM130 nm CMOS technology to reduce size. The identification
      system including bond pads has a size of 1.2 mm * 0.8 mm.

PMID- 25570660
TI  - Decision support for stroke rehabilitation therapy via describable attribute
      based decision trees.
AB  - This paper proposes a computational framework for movement quality assessment
      using a decision tree model that can potentially assist a physical therapist in a
      telerehabilitation context. Using a dataset of key kinematic attributes collected
      from eight stroke survivors, we demonstrate that the framework can be reliably
      used for movement quality assessment of a reach-to-grasp cone task, an activity
      commonly used in upper extremity stroke rehabilitation therapy. The proposed
      framework is capable of providing movement quality scores that are highly
      correlated to the ratings provided by therapists, who used a custom rating rubric
      created by rehabilitation experts. Our hypothesis is that a decision tree model
      could be easily utilized by therapists as a potential assistive tool, especially
      in evaluating movement quality on a large-scale dataset collected during
      unsupervised rehabilitation (e.g., training at the home), thereby reducing the
      time and cost of rehabilitation treatment.

PMID- 25570661
TI  - Physiological trajectory of patients pre and post ICU discharge.
AB  - The intensive care unit (ICU) admits the most severely ill patients, and the goal
      of the unit can be interpreted as stabilizing patient physiology. Once these
      patients are discharged from the ICU to a step-down ward, they continue to have
      their vital signs monitored by nursing staff. Early detection of physiological
      deterioration has been highlighted as a key step to reduce ICU readmission and
      improve patient outcomes. Vital signs were collected for a dataset of 98 patients
      admitted to an ICU and who survived to hospital discharge after their stay on a
      step-down ward. A model of physiological normality was developed using data from
      the day of hospital discharge, and patients were retrospectively evaluated
      throughout their stay using this model. We show that the physiology of patients
      being cared for in the ICU improves very rapidly in the three days prior to
      discharge, and furthermore, that this recovery continues during their stay on the
      ward, albeit at a slower rate. 

PMID- 25570662
TI  - Personalized alerts for patients with COPD using pulse oximetry and symptom
      scores.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a progressive chronic disease,
      predicted to become the third leading cause of death by 2030. COPD patients are
      at risk of sudden and acute worsening of symptoms, reducing the patient's quality
      of life and leading to hospitalization. We present the results of a pilot study
      with 18 COPD patients using an m-Health system, based on a tablet computer and
      pulse oximeter, for a period of six months. For prioritizing patients for
      clinical review, a data-driven approach has been developed which generates
      personalized alerts using the electronic symptom diary, pulse rate, blood oxygen
      saturation, and respiratory rate derived from oximetry data. This work examines
      the advantages of multivariate novelty detection over univariate approaches and
      shows the benefit of including respiratory rate as a predictor. 

PMID- 25570663
TI  - Telemonitoring in heart failure patients with clinical decision support to
      optimize medication doses based on guidelines.
AB  - The European Society of Cardiology guidelines for heart failure management are
      based on strong evidence that adherence to optimal medication is beneficial for
      heart failure patients. Telemonitoring with integrated clinical decision support
      enables physicians to adapt medication dose based on up to date vital parameters
      and reduces the number of hospital visits needed solely for up-titration of heart
      failure medication. Although keeping track of weight and blood pressure changes
      is recommended during unstable phases, e.g. post-discharge and during up
      titration of medication, guidelines are rather vague regarding telehealth
      aspects. In this paper, we focus on the evaluation of a clinical decision support
      system for adaption of heart failure medication and for detecting early
      deteriorations through monitoring of blood pressure, heart rate and weight
      changes. This clinical decision support system is currently used in INTENSE-HF, a
      large scale telemonitoring trial with heart failure patients. The aim of this
      paper was to apply the decision support algorithm to an existing telemonitoring
      dataset, to assess the ability of the decision support concept to adhere to the
      guidelines and to discuss its limitations and potential improvements. 

PMID- 25570664
TI  - A dynamic Bayesian network approach for time-specific survival probability
      prediction in patients after ventricular assist device implantation.
AB  - In this work we present a decision support tool for the calculation of time
      dependent survival probability for patients after ventricular assist device
      implantation. Two different models have been developed, a short term one which
      predicts survival for the first three months and a long term one that predicts
      survival for one year after implantation. In order to model the time dependencies
      between the different time slices of the problem, a dynamic Bayesian network
      (DBN) approach has been employed. DBNs order to capture the temporal events of
      the patient disease and the temporal data availability. High accuracy results
      have been reported for both models. The short and long term DBNs reached an
      accuracy of 96.97% and 93.55% respectively. 

PMID- 25570665
TI  - Disease state fingerprint for fall risk assessment.
AB  - Fall prevention is an important and complex multifactorial challenge, since one
      third of people over 65 years old fall at least once every year. A novel
      application of Disease State Fingerprint (DSF) algorithm is presented for
      holistic visualization of fall risk factors and identifying persons with falls
      history or decreased level of physical functioning based on fall risk assessment
      data. The algorithm is tested with data from 42 older adults, that went through a
      comprehensive fall risk assessment. Within the study population the Activities
      specific Balance Confidence (ABC) scale score, Berg Balance Scale (BBS) score and
      the number of drugs in use were the three most relevant variables, that differed
      between the fallers and non-fallers. This study showed that the DSF visualization
      is beneficial in inspection of an individual's significant fall risk factors,
      since people have problems in different areas and one single assessment scale is
      not enough to expose all the people at risk. 

PMID- 25570666
TI  - WELCOME - innovative integrated care platform using wearable sensing and smart
      cloud computing for COPD patients with comorbidities.
AB  - We propose WELCOME, an innovative integrated care platform using wearable sensors
      and smart cloud computing for Chronic Obstructive Pulmonary Disease (COPD)
      patients with co-morbidities. WELCOME aims to bring about a change in the
      reactive nature of the management of chronic diseases and its comorbidities, in
      particular through the development of a patient centred and proactive approach to
      COPD management. The aim of WELCOME is to support healthcare services to give
      early detection of complications (potentially reducing hospitalisations) and the
      prevention and mitigation of comorbidities (Heart Failure, Diabetes, Anxiety and
      Depression). The system incorporates patient hub, where it interacts with the
      patient via a light vest including a large number of non-invasive chest sensors
      for monitoring various relevant parameters. In addition, interactive applications
      to monitor and manage diabetes, anxiety and lifestyle issues will be provided to
      the patient. Informal carers will also be supported in dealing with their
      patients. On the other hand, welcome smart cloud platform is the heart of the
      proposed system where all the medical records and the monitoring data are managed
      and processed via the decision support system. Healthcare professionals will be
      able to securely access the WELCOME applications to monitor and manage the
      patient's conditions and respond to alerts on personalized level. 

PMID- 25570667
TI  - Metabolic rate monitoring and weight reduction/management.
AB  - Engineering research may provide tools to the individual as well as to the public
      in general, to effectively monitor wellness and health patterns, such as
      metabolic rate and weight control. Ketone bodies and acetone gas emissions in
      exhaled breath and skin, in particular, may be used as biomarkers of fatty acid
      metabolism and may be used in diet control. Two types of technologies, resistive
      chemosensors and chemomechanical actuators are outlined here as examples of such
      tools currently under development and of great promise. 

PMID- 25570668
TI  - Sensors and systems for obesity care and research.
AB  - Obesity and overweight decrease the quality and length of life and increases
      healthcare costs. Dramatic increase of obesity, particularly childhood obesity,
      in developed countries requires efficient methods and systems for obesity
      research and monitoring of users. New generation of smart sensors and ubiquitous
      monitoring systems provide unprecedented opportunities to assess real-life
      environments, mobility, physical activity, and physiological responses. In this
      paper we present current trends in sensing, social networks, and systems
      integration. New monitoring and intervention technologies create new
      opportunities for remote patient monitoring and intervention. 

PMID- 25570669
TI  - Decoding underlying brain activities in time and frequency domains through
      complex independent component analysis of EEG signals.
AB  - Brain activities are often investigated through Electroencephalographic (EEG)
      data analysis using time-domain Independent Component Analysis (ICA).
      Nevertheless, the instantaneous mixing model of ICA cannot properly describe
      spatio-temporal dynamics, such as those related to traveling waves of neural
      activity. In this work, we exploit the application of the Complex ICA (cICA) to
      describe the underlying brain activities in time and frequency domain. In
      particular, we show how to effectively extract the most significant time
      frequency structure of cortical activity in order to solve a compelling EEG-based
      pattern classification problem. The crucial step of independent component
      selection among frequencies is performed using an objective computational method
      based on template matching techniques with physiologically-plausible activations.
      Experimental results are obtained using on-line EEG data from the BCI Competition
      2003 and are expressed in terms of confusion matrix after leave-one-out
      validation procedure. A comparative analysis between ICA and cICA models reveals
      that cICA estimation gives powerful information and allows to achieve a higher
      classification accuracy with respect to instantaneous ICA. 

PMID- 25570670
TI  - A novel approach for baseline correction in 1H-MRS signals based on ensemble
      empirical mode decomposition.
AB  - Proton magnetic resonance spectroscopy ((1)H-MRS) is a non-invasive diagnostic
      tool for measuring biochemical changes in the human body. Acquired (1)H-MRS
      signals may be corrupted due to a wideband baseline signal generated by
      macromolecules. Recently, several methods have been developed for the correction
      of such baseline signals, however most of them are not able to estimate baseline
      in complex overlapped signal. In this study, a novel automatic baseline
      correction method is proposed for (1)H-MRS spectra based on ensemble empirical
      mode decomposition (EEMD). This investigation was applied on both the simulated
      data and the in-vivo (1)H-MRS of human brain signals. Results justify the
      efficiency of the proposed method to remove the baseline from (1)H-MRS signals. 

PMID- 25570672
TI  - Respiratory rate detection by empirical mode decomposition method applied to
      diaphragm mechanomyographic signals.
AB  - Non-invasive evaluation of respiratory activity is an area of increasing research
      interest, resulting in the appearance of new monitoring techniques, ones of these
      being based on the analysis of the diaphragm mechanomyographic (MMGdi) signal.
      The MMGdi signal can be decomposed into two parts: (1) a high frequency activity
      corresponding to lateral vibration of respiratory muscles, and (2) a low
      frequency activity related to excursion of the thoracic cage. The purpose of this
      study was to apply the empirical mode decomposition (EMD) method to obtain the
      low frequency of MMGdi signal and selecting the intrinsic mode functions related
      to the respiratory movement. With this intention, MMGdi signals were acquired
      from a healthy subject, during an incremental load respiratory test, by means of
      two capacitive accelerometers located at left and right sides of rib cage.
      Subsequently, both signals were combined to obtain a new signal which contains
      the contribution of both sides of thoracic cage. Respiratory rate (RR) measured
      from the mechanical activity (RR(MMG)) was compared with that measured from
      inspiratory pressure signal (RR(P)). Results showed a Pearson's correlation
      coefficient (r = 0.87) and a good agreement (mean bias = -0.21 with lower and
      upper limits of -2.33 and 1.89 breaths per minute, respectively) between RR(MMG)
      and RR(P) measurements. In conclusion, this study suggests that RR can be
      estimated using EMD for extracting respiratory movement from low mechanical
      activity, during an inspiratory test protocol.

PMID- 25570671
TI  - Assessing in vitro cytotoxicity of cell micromotion by Hilbert-Huang transform.
AB  - Electric cell-substrate impedance sensing (ECIS) is a powerful instrument for
      quantifying cell behavior in tissue culture. As cells attach and spread on the
      sensing electrode, they restrict the current flow and hence cause the increase of
      electrical impedance. Furthermore, cell motion may reveal itself as electrical
      fluctuations, which are always associated with living cells and continue even
      when the cells become fully confluent. The impedance fluctuation is attributed to
      incessant changes in the size of the cell-substrate space as cells persistently
      rearrange their cell-substrate adhesion sites. The magnitude of this sort of
      vertical motion detected by ECIS is of the order of nanometers and referred to as
      micromotion. In this study, Hilbert-Huang Transform was used as a micromotion
      analysis tool to distinguish the in vitro cytotoxicity of human umbilical vein
      endothelial cells (HUVECs) exposed to low levels of cytochalasin B. Hilbert-Huang
      Transform consists of two procedures: the empirical mode decomposition (EMD) and
      the Hilbert Transform. The measured impedance fluctuations due to cell
      micromotion were decomposed into several intrinsic mode functions (IMFs) by EMD,
      and then these IMFs were transferred to instantaneous frequencies by Hilbert
      Transform. Both amplitude and phase of instantaneous frequencies were expressed
      as a time-frequency spectrum, called Hilbert spectrum, which displayed different
      distribution pattern in response to different cytochalasin B concentration. The
      total instantaneous energy (IE) of each IMF was also calculated to quantify the
      spectral difference. In addition to the observation of a dose-dependent
      relationship, the IE value of the first IMF at 0.1 MUM decreased to about 48% of
      the control value and significantly distinguished the cytotoxic effect of 0.1 MUM
      of cytochalasin B (P<0.05).

PMID- 25570673
TI  - Signed-gradient adaptive step size LMS algorithm for biomedical applications.
AB  - Gradient adaptive step size adaptive filters have been widely used to adapt
      different biomedical application environments and obtain useful life signals from
      serious ambient noise and interferences. In order to further improve the signal
      to-noise ratio (SNR) of the life signals, this paper presents a class of signed
      gradient adaptive step size least mean square (LMS) adaptive filters. The
      proposed algorithms introduce a sign function to replace the gradient of squared
      error in the step size updating process of the gradient adaptive step size LMS
      adaptive filters. The performance of both gradient and signed-gradient algorithms
      with dual adaptive filters is compared by extracting heartbeat signals from
      ambient noise in stethoscopes. Simulation results demonstrate that though the
      signed-gradient adaptive step size LMS algorithm converges at a slower rate at
      the early stage of iteration, it has a smaller mean squared error (MSE) at the
      stage of convergence, thus achieves a higher SNR. 

PMID- 25570674
TI  - Adaptive thresholding with inverted triangular area for real-time detection of
      the heart rate from photoplethysmogram traces on a smartphone.
AB  - Photoplethysmogram (PPG) signals acquired by smartphone cameras are weaker than
      those acquired by dedicated pulse oximeters. Furthermore, the signals have lower
      sampling rates, have notches in the waveform and are more severely affected by
      baseline drift, leading to specific morphological characteristics. This paper
      introduces a new feature, the inverted triangular area, to address these specific
      characteristics. The new feature enables real-time adaptive waveform detection
      using an algorithm of linear time complexity. It can also recognize notches in
      the waveform and it is inherently robust to baseline drift. An implementation of
      the algorithm on Android is available for free download. We collected data from
      24 volunteers and compared our algorithm in peak detection with two competing
      algorithms designed for PPG signals, Incremental-Merge Segmentation (IMS) and
      Adaptive Thresholding (ADT). A sensitivity of 98.0% and a positive predictive
      value of 98.8% were obtained, which were 7.7% higher than the IMS algorithm in
      sensitivity, and 8.3% higher than the ADT algorithm in positive predictive value.
      The experimental results confirmed the applicability of the proposed method.

PMID- 25570675
TI  - Cancellation of motion artifact induced by exercise for PPG-based heart rate
      sensing.
AB  - Heart rate (HR) sensing during exercise is essential for medical, healthcare and
      sport physiological purposes. Photo-Plethysmo-Graphy (PPG) is a simple and non
      invasive technique for HR sensing, but it is highly sensitive to motion artifact.
      This paper proposes a cancellation technique of motion artifact in PPG-based HR
      sensing for a man during exercise. The canceller is equipped with two sensors;
      one is a normal PPG sensor where an LED/Photo-Detector (PD) contacts the skin to
      detect Blood Volume Pulse (BVP) (+motion artifact) and the other is a motion
      artifact sensor where an LED/PD does not contact the skin to detect only motion
      artifact. Experimental results show that the proposed technique, which is
      implemented in adaptive algorithms, can sense HR correctly by cancelling motion
      artifact induced by exercises such as running and jumping. 

PMID- 25570676
TI  - Parallel feedback active noise control of MRI acoustic noise with signal
      decomposition using hybrid RLS-NLMS adaptive algorithms.
AB  - This paper presents a cost-effective adaptive feedback Active Noise Control
      (FANC) method for controlling functional Magnetic Resonance Imaging (fMRI)
      acoustic noise by decomposing it into dominant periodic components and residual
      random components. Periodicity of fMRI acoustic noise is exploited by using
      linear prediction (LP) filtering to achieve signal decomposition. A hybrid
      combination of adaptive filters-Recursive Least Squares (RLS) and Normalized
      Least Mean Squares (NLMS) are then used to effectively control each component
      separately. Performance of the proposed FANC system is analyzed and Noise
      attenuation levels (NAL) up to 32.27 dB obtained by simulation are presented
      which confirm the effectiveness of the proposed FANC method.

PMID- 25570677
TI  - Conceptual model of arterial tree based on solitons by compartments.
AB  - Models define a simplification of reality, which help to understand function. The
      arterial system has been modeled in many ways: lumped models, tube models and
      anatomically based distributed models. In this work, arterial segments were
      modeled as thin nonlinear elastic tubes filled with an incompressible fluid,
      whose governing dynamics were denoted by the Korteweg and DeVries equation. In
      order characterize the pressure pulse propagation, a discrete multi-segmented
      conduit was proposed. Arterial wall mechanical parameters were obtained from
      existing literature and assigned to each individual segment. The numerical model
      was developed starting in the aortic arch, and ending at the femoral artery. The
      main idea of this article was to perform a computational simulation of pressure
      wave propagation, considered as a solitons combination, along several segments of
      the arterial tree. 

PMID- 25570678
TI  - Intrinsic dimensionality of extracellular action potentials.
AB  - Linear approaches to low-dimensional feature extraction may not be appropriate
      when statistical data are generated by a nonlinear interaction of parameters.
      Equally inadequate are linear methods for determining the dimension of the
      feature space. This article estimates the intrinsic dimension of extracellular
      action potentials (EAPs), which can be viewed as the minimum number of
      nonlinearly interacting parameters sufficient to describe the data. When combined
      with nonlinear feature extraction methods, this information may lead to a more
      faithful, low-dimensional EAP representation. These points are demonstrated using
      EAPs recorded experimentally by a multisensor electrode. 

PMID- 25570679
TI  - Artificial neural network prediction of specific VOCs and blended VOCs for
      various concentrations from the olfactory receptor firing rates of Drosophila
      melanogaster.
AB  - In our previous work, we have investigated the classification of odorants based
      on their chemical classes only, e.g. Alcohol, Terpene or Ester, using Artificial
      Neural Networks (ANN) as the signal processing backend of an insect olfactory
      electronic nose, or e-nose. However, potential applications of e-noses in the
      food and beverage industry which include the assessment of a fruit's ripeness,
      quality of wines or identifying bacterial contamination in products, demand the
      ability to predict beyond chemical class and to identify exact chemicals, known
      as specific Volatile Organic Compounds (VOCs) and blends of chemical that present
      themselves as aromas, known as blended VOCs (BVOCs). In this work, we demonstrate
      for the first time how it is possible to predict such VOCs and also BVOCs at
      varying concentration levels. We achieve this goal by using ANNs in the form of
      hybrid Multi-Layer Perceptrons (MLPs), to analyze the firing rate responses of
      the model organism Drosophila melanogaster's odorant receptors (DmOrs), in order
      to predict the specific VOCs and BVOCs. We report for the raw and noise injected
      data how the highest MLP prediction for specific VOCs occurred at a 10(-4)mol.dm(
      3) concentration in which all the VOC validation vectors were identified and at a
      concentration of 10(-2)mol.dm(-3) for BVOCs in which 8/9 or 88.9% were
      identified. The results demonstrate for the first time the power of using MLPs
      and insect odorant receptors (Ors) to predict specific VOCs and BVOCs. 

PMID- 25570680
TI  - Arrhythmia detection in single-lead ECG by combining beat and rhythm-level
      information.
AB  - In this paper, we propose a method for detecting arrhythmia in single-lead
      electro-cardiogram (ECG) signal. By applying a sequence of pre-processing steps
      (filtering, baseline correction), beat classification and rhythm identification,
      six different beat-types and four abnormal rhythms are detected. Beat
      classification uses fast Fourier transform (FFT) as the feature and a support
      vector machine (SVM) classifier. Subsequently rhythm identification uses a
      deterministic finite state machine to detect abnormal rhythms. We evaluate the
      performance of our technique on the MIT-BIH database, to obtain 97% beat
      classification accuracy and perfect rhythm identification result. 

PMID- 25570681
TI  - Amplitude normalization applied to an artificial neural network-based automatic
      sleep spindle detection system.
AB  - Sleep spindles are significant rhythmic transients present in the sleep
      electroencephalogram (EEG) of non-rapid eye movement (NREM) sleep. Automatic
      sleep spindle detection techniques are sought for the automation of sleep staging
      and the detailed study of sleep spindle patterns, of possible physiological
      significance. A deficiency of many of the available automatic detection
      techniques is their reliance on the amplitude level of the recorded EEG voltage
      values. In the present work, an automatic sleep spindle detection system that has
      been previously proposed, using a Multi-Layer Perceptron (MLP) Artificial Neural
      Network (ANN), was evaluated using a voltage amplitude normalization procedure,
      with the aim of making the performance of the ANN independent of the absolute
      voltage level of the individual subjects' recordings. The application of the
      normalization procedure led to a reduction in the false positive rate (FPR) as
      well as in the sensitivity. When the ANN was trained on a combination of data
      from healthy subjects, the reduction of FPR was from 42.6% to 19%, while the
      sensitivity of the ANN was kept at acceptable levels, i.e., 73.4% for the
      normalized procedure vs 84.6% for the non-normalized procedure. 

PMID- 25570682
TI  - Exploring embedding matrices and the entropy gradient for the segmentation of
      heart sounds in real noisy environments.
AB  - In this paper we explore a novel feature for the segmentation of heart sounds:
      the entropy gradient. We are motivated by the fact that auscultations in real
      environments are highly contaminated by noise and results reinforce our
      suspicions that the entropy gradient is not only robust to such noise but
      maintains a high sensitivity to the S1 and S2 components of the signal. Our whole
      approach consists of three stages, out of which the last two are novel
      contributions to this field. The first stage consists of typical pre-processing
      and wavelet reconstruction to obtain the Shannon energy envelogram. On the second
      stage we use an embedding matrix to track the dynamics of the system, which is
      formed by delay vectors with higher dimension than the corresponding attractor.
      On the third stage, we use the eigenvalues and eigenvectors of the embedding
      matrix to estimate the entropy of the envelogram. Finite differences are used to
      estimate entropy gradients, in which standard peak picking approaches are used
      for heart sound segmentation. Experiments are performed on a public dataset of
      pediatric auscultations obtained in real environments and results show the
      promising potential of this novel feature for such noisy scenarios. 

PMID- 25570683
TI  - Dynamic tension EMG to characterize the effects of DBS treatment of advanced
      Parkinson's disease.
AB  - Deep brain stimulation (DBS) is an effective treatment method for motor symptoms
      of advanced Parkinson's disease. DBS-electrode is implanted to subthalamic
      nucleus to give precisely allocated electrical stimuli to brain. The optimal
      stimulus type has to be adjusted individually. Disease severity, main symptoms
      and biological factors play a role in correctly setting up the device. Currently
      there are no objective methods to assess the efficacy of DBS, hence the
      adjustment is based solely on clinical assessment. In optimal case an objectively
      measurable feature would point the right settings of DBS. Surface
      electromyographic and kinematic measurements have been used in Parkinson's
      disease research. As Parkinson's disease symptoms are known to change the EMG
      signal properties, these methods could be helpful aid in the clinical adjustment
      of DBS. In this study, 13 patients with advanced Parkinson's disease who received
      DBS treatment were measured. The patients were measured with seven different
      settings of the DBS in clinical range including changes in stimulation amplitude,
      frequency and pulse width. The EMG analysis was based on parameters that
      characterize EMG signal morphology. Correlation dimension and recurrence rate
      made the most significant difference in relation to optimal settings. In
      conclusion, EMG analysis is able to detect differences between the DBS setups,
      and can help in finding the correct parameters. 

PMID- 25570684
TI  - Non-linear HRV indices under autonomic nervous system blockade.
AB  - Heart rate variability (HRV) has been studied as a non-invasive technique to
      characterize the autonomic nervous system (ANS) regulation of the heart. Non
      linear methods based on chaos theory have been used during the last decades as
      markers for risk stratification. However, interpretation of these nonlinear
      methods in terms of sympathetic and parasympathetic activity is not fully
      established. In this work we study linear and non-linear HRV indices during ANS
      blockades in order to assess their relation with sympathetic and parasympathetic
      activities. Power spectral content in low frequency (0.04-0.15 Hz) and high
      frequency (0.15-0.4 Hz) bands of HRV, as well as correlation dimension, sample
      and approximate entropies were computed in a database of subjects during single
      and dual ANS blockade with atropine and/or propranolol. Parasympathetic blockade
      caused a significant decrease in the low and high frequency power of HRV, as well
      as in correlation dimension and sample and approximate entropies. Sympathetic
      blockade caused a significant increase in approximate entropy. Sympathetic
      activation due to postural change from supine to standing caused a significant
      decrease in all the investigated non-linear indices and a significant increase in
      the normalized power in the low frequency band. The other investigated linear
      indices did not show significant changes. Results suggest that parasympathetic
      activity has a direct relation with sample and approximate entropies.

PMID- 25570685
TI  - Novel feature extraction method based on weight difference of weighted network
      for epileptic seizure detection.
AB  - The extraction method of classification feature is primary and core problem in
      all epileptic EEG detection algorithms, since it can seriously affect the
      performance of the detection algorithm. In this paper, a novel epileptic EEG
      feature extraction method based on the statistical parameter of weighted complex
      network is proposed. The EEG signal is first transformed into weighted network
      and the weight differences of all the nodes in the network are analyzed. Then the
      sum of top quintile weight differences is extracted as the classification
      feature. At last, the extracted feature is applied to classify the epileptic EEG
      dataset. Experimental results show that the single feature classification based
      on the extracted feature obtains higher classification accuracy up to 94.75%,
      which indicates that the extracted feature can distinguish the ictal EEG from
      interictal EEG and has great potentiality of real-time epileptic seizures
      detection. 

PMID- 25570687
TI  - Cross-correlation based MUECoG waveform tracking.
AB  - Clinical electrodes for epileptic seizure monitoring traditionally require a
      tradeoff between coverage area and spatial resolution. However, with multiplexed,
      flexible array devices, high spatial resolution is possible over large surface
      areas. This high resolution data, recorded from 360 electrodes or more, is
      difficult to review manually for subtle patterns. Here we develop innovative
      methods for visualizing micro-electrocorticography (MUECoG) datasets. The data
      contains seizure and non-seizure dynamics that can be used to better understand
      how seizures begin, progress, and end. Novel visualization techniques allow the
      researcher to better understand the data by arranging it in accessible ways. This
      paper presents tools to visualize a seizure waveform's velocity and location over
      a given window of time. 

PMID- 25570686
TI  - Surface EMG parameters in schizophrenia patients.
AB  - The aim of the study was to compare a variety of surface EMG (sEMG) parameters in
      several groups of schizophrenia (SZ, n=69) patients and healthy controls (n=44).
      We computed spectral, mutual information (MI) based and recurrence quantification
      analysis (RQA) parameters of sEMG. The major finding is that sEMG of the controls
      had higher values of the MI-based parameter, mean and median spectrum
      frequencies, and lower values of most of RQA parameters. It means higher content
      of recurrent fragments in sEMG of SZ patients. We suggest that the differences
      might be caused by either denervation/renervation process of single muscle fibers
      in SZ patients and/or by increased motor unit synchronization induced by
      antipsychotic therapy. 

PMID- 25570689
TI  - Comparison study of seizure detection using stationary and nonstationary methods.
AB  - We present an accurate seizure detection algorithm, and make a detailed
      comparison of two frequency analysis methods: a widely used stationary method -
      Fast Fourier Transform (FFT) and a relatively new nonstationary method - Hilbert
      Huang Transform (HHT). Two public databases and one our own database were tested.
      The results show that our algorithm has very high accuracy compared with the
      state-of-the-art. More interestingly, it shows that the nonstationary method HHT
      offers better performance than the stationary method FFT in seizure detection.
      Therefore we propose that we should pay attention to the nonstationarity of EEG
      signal, since the "stationary assumption" may introduce some inaccuracy. 

PMID- 25570688
TI  - The mixing rate of the arterial blood pressure waveform Markov chain is
      correlated with shock index during hemorrhage in anesthetized swine.
AB  - Identifying the need for interventions during hemorrhage is complicated due to
      physiological compensation mechanisms that can stabilize vital signs until a
      significant amount of blood loss. Physiological systems providing compensation
      during hemorrhage affect the arterial blood pressure waveform through changes in
      dynamics and waveform morphology. We investigated the use of Markov chain
      analysis of the arterial blood pressure waveform to monitor physiological systems
      changes during hemorrhage. Continuous arterial blood pressure recordings were
      made on anesthetized swine (N=7) during a 5 min baseline period and during a slow
      hemorrhage (10 ml/kg over 30 min). Markov chain analysis was applied to 20 sec
      arterial blood pressure waveform segments with a sliding window. 20 ranges of
      arterial blood pressure were defined as states and empirical transition
      probability matrices were determined for each 20 sec segment. The mixing rate
      (2(nd) largest eigenvalue of the transition probability matrix) was determined
      for all segments. A change in the mixing rate from baseline estimates was
      identified during hemorrhage for each animal (median time of 13 min, ~10%
      estimated blood volume, with minimum and maximum times of 2 and 33 min,
      respectively). The mixing rate was found to have an inverse correlation with
      shock index for all 7 animals (median correlation coefficient of -0.95 with
      minimum and maximum of -0.98 and -0.58, respectively). The Markov chain mixing
      rate of arterial blood pressure recordings is a novel potential biomarker for
      monitoring and understanding physiological systems during hemorrhage. 

PMID- 25570690
TI  - Analysis of progression of fatigue conditions in biceps brachii muscles using
      surface electromyography signals and complexity based features.
AB  - Muscle fatigue is a neuromuscular condition where muscle performance decreases
      due to sustained or intense contraction. It is experienced by both normal and
      abnormal subjects. In this work, an attempt has been made to analyze the
      progression of muscle fatigue in biceps brachii muscles using surface
      electromyography (sEMG) signals. The sEMG signals are recorded from fifty healthy
      volunteers during dynamic contractions under well defined protocol. The acquired
      signals are preprocessed and segmented in to six equal parts for further
      analysis. The features, such as activity, mobility, complexity, sample entropy
      and spectral entropy are extracted from all six zones. The results are found
      showing that the extracted features except complexity feature have significant
      variations in differentiating non-fatigue and fatigue zone respectively. Thus, it
      appears that, these features are useful in automated analysis of various
      neuromuscular activities in normal and pathological conditions. 

PMID- 25570691
TI  - Motion artifact reduction in PPG signals from face: face tracking & stochastic
      state space modeling approach.
AB  - The Photoplethymography(PPG) is generally measured on a finger or an ear using
      contact sensors. The recent several studies using non-contact sensor such as CCD
      camera and web-cam to measure PPG have been introduced. However the motion
      artifact issue is also emerging in non-contact camera sensing similar to contact
      type one because it is sensitive to artifacts generated by subject's head and
      body motion. In this paper, the two sequential approaches for a motion artifact
      reduction algorithm are presented; the one is a face tracking method that detects
      and tracks the skin region of face which is containing PPG signals, the other is
      the reduction method of motion artifact due to various head & face movement such
      as roll, yaw, pitch, translation and scale. Results of the proposed KF are
      compared to these of the FIR band pass filter(BPF). 

PMID- 25570692
TI  - Identification of ankle joint stiffness from short segments of data: application
      to passive dynamics during movement.
AB  - This paper presents a state-space (subspace) method for identification of
      parallel-cascade joint stiffness from short segments of data. It provides
      unbiased estimates of stiffness by accounting for the contributions of initial
      conditions of each segment. The method is important in situations where it is not
      possible to acquire a long stationary data due to switching or time-varying
      behavior. The power of the method was demonstrated by using it to efficiently
      characterize ankle joint stiffness through the joint's range of motion. 

PMID- 25570693
TI  - Assessing instantaneous energy in the EEG: a non-negative, frequency-weighted
      energy operator.
AB  - Signal processing measures of instantaneous energy typically include only
      amplitude information. But measures that include both amplitude and frequency do
      better at assessing the energy required by the system to generate the signal,
      making them more sensitive measures to include in electroencephalogram (EEG)
      analysis. The Teager-Kaiser operator is a frequency-weighted measure that is
      frequently used in EEG analysis, although the operator is poorly defined in terms
      of common signal processing concepts. We propose an alternative frequency
      weighted energy measure that uses the envelope of the derivative of the signal.
      This simple envelope- derivative operator has the advantage of being nonnegative,
      which when applied to a detection application in newborn EEG improves performance
      over the Teager-Kaiser operator: without post-processing filters, area-under the
      receiver-operating characteristic curve (AUC) is 0.57 for the Teager-Kaiser
      operator and 0.80 for the envelope-derivative operator. The envelope-derivative
      operator also satisfies important properties, similar to the Teager-Kaiser
      operator, such as tracking instantaneous amplitude and frequency. 

PMID- 25570694
TI  - Muscle artifacts in single trial EEG data distinguish patients with Parkinson's
      disease from healthy individuals.
AB  - Parkinson's disease (PD) is known to lead to marked alterations in cortical-basal
      ganglia activity that may be amenable to serve as a biomarker for PD diagnosis.
      Using non-linear delay differential equations (DDE) for classification of PD
      patients on and off dopaminergic therapy (PD-on, PD-off, respectively) from
      healthy age-matched controls (CO), we show that 1 second of quasi-resting state
      clean and raw electroencephalogram (EEG) data can be used to classify CO from PD
      on/off based on the area under the receiver operating characteristic curve
      (AROC). Raw EEG is shown to classify more robustly (AROC=0.59-0.86) than clean
      EEG data (AROC=0.57-0.72). Decomposition of the raw data into stereotypical and
      non-stereotypical artifacts provides evidence that increased classification of
      raw EEG time series originates from muscle artifacts. Thus, non-linear feature
      extraction and classification of raw EEG data in a low dimensional feature space
      is a potential biomarker for Parkinson's disease. 

PMID- 25570695
TI  - An optimized ultrasound digital beamformer with dynamic focusing implemented on
      FPGA.
AB  - We present a resource-optimized dynamic digital beamformer for an ultrasound
      system based on a field-programmable gate array (FPGA). A comprehensive 64
      channel receive beamformer with full dynamic focusing is embedded in the Altera
      Arria V FPGA chip. To improve spatial and contrast resolution, full dynamic
      beamforming is implemented by a novel method with resource optimization. This was
      conceived using the implementation of the delay summation through a bulk (coarse)
      delay and fractional (fine) delay. The sampling frequency is 40 MHz and the
      beamformer includes a 240 MHz polyphase filter that enhances the temporal
      resolution of the system while relaxing the Analog-to-Digital converter (ADC)
      bandwidth requirement. The results indicate that our 64-channel dynamic
      beamformer architecture is amenable for a low power FPGA-based implementation in
      a portable ultrasound system. 

PMID- 25570696
TI  - Correlation mapping for visualizing propagation of pulsatile CSF motion in
      intracranial space based on magnetic resonance phase contrast velocity images:
      preliminary results.
AB  - Correlation time mapping based on magnetic resonance (MR) velocimetry has been
      applied to pulsatile cerebrospinal fluid (CSF) motion to visualize the pressure
      transmission between CSF at different locations and/or between CSF and arterial
      blood flow. Healthy volunteer experiments demonstrated that the technique
      exhibited transmitting pulsatile CSF motion from CSF space in the vicinity of
      blood vessels with short delay and relatively high correlation coefficients.
      Patient and healthy volunteer experiments indicated that the properties of CSF
      motion were different from the healthy volunteers. Resultant images in healthy
      volunteers implied that there were slight individual difference in the CSF
      driving source locations. Clinical interpretation for these preliminary results
      is required to apply the present technique for classifying status of
      hydrocephalus. 

PMID- 25570697
TI  - 3D imaging of microbial biofilms: integration of synchrotron imaging and an
      interactive visualization interface.
AB  - Understanding the structure of microbial biofilms and other complex microbial
      communities is now possible through x-ray microtomography imaging. Feature
      detection and image processing for this type of data focuses on efficiently
      identifying and segmenting biofilm biomass in the datasets. These datasets are
      very large and segmentation often requires manual interventions due to low
      contrast between objects and high noise levels. New software is required for the
      effectual interpretation and analysis of such data. This work specifies the
      evolution and ability to analyze and visualize high resolution x-ray
      microtomography datasets. Major functionalities include read/write with multiple
      popular file formats, down-sampling large datasets to generate quick-views on low
      power computers, image processing, and generating high quality output images and
      videos. These capabilities have been wrapped into a new interactive software
      toolkit, BiofilmViewer. A major focus of our work is to facilitate data transfer
      and to utilize the capabilities of existing powerful visualization and analytical
      tools including MATLAB, ImageJ, Paraview, Chimera, Vaa3D, Cell Profiler, Icy,
      BioImageXD, and Drishti. 

PMID- 25570698
TI  - GPU based multi-histogram volume navigation for virtual bronchoscopy.
AB  - An interactive navigation system for virtual bronchoscopy is presented, which is
      based solely on GPU based high performance multi-histogram volume rendering. 

PMID- 25570699
TI  - Brain activation inhomogeneity highlighted by the Isotropic Anomalous Diffusion
      filter.
AB  - The visual appealing nature of the now popular BOLD fMRI may give the false
      impression of extreme simplicity, as if the the functional maps could be
      generated with the press of a single button. However, one can only get plausible
      maps after long and cautious processing, considering that time and noise come
      into play during acquisition. One of the most popular ways to account for noise
      and individual variability in fMRI is the use of a Gaussian spatial filter.
      Although very robust, this filter may introduce excessive blurring, given the
      strong dependence of results on the central voxel value. Here, we propose the use
      of the Isotropic Anomalous Diffusion (IAD) approach, aiming to reduce excessive
      homogeneity while retaining the natural variability of signal across brain space.
      We found differences between Gaussian and IAD filters in two parameters gathered
      from Independent Component maps (ICA), identified on brain areas responsible for
      auditory processing during rest. Analysis of data gathered from 7 control
      subjects shows that the IAD filter rendered more localized active areas and
      higher contrast-to-noise ratios, when compared to equivalent Gaussian filtered
      data (Student t-test, p<0.05). The results seem promising, since the anomalous
      filter performs satisfactorily in filtering noise with less distortion of
      individual localized brain responses.

PMID- 25570700
TI  - Evaluating perceptual maps of asymmetries for gait symmetry quantification and
      pathology detection.
AB  - The gait movement is a complex and essential process of the human activity. Yet,
      many types of diseases (neurological, muscular, orthopedic, etc.) can be
      diagnosed from the gait analysis. This paper introduces a novel method to quickly
      visualize the different body parts related to an (temporally shift-invariant)
      asymmetric movement in the human gait of a patient for daily clinical usage. The
      goal is to provide a cheap and easy-to-use method that measures the gait
      asymmetry and display results in a perceptual and intuitive way. This method
      relies on an affordable consumer depth sensor, the Kinect, which is very suitable
      for small room and fast diagnostic, since it is easy to setup and marker-less. 

PMID- 25570701
TI  - Estimating blur at the brain gray-white matter boundary for FCD detection in MRI.
AB  - Focal cortical dysplasia (FCD) is a frequent cause of epilepsy and can be
      detected using brain magnetic resonance imaging (MRI). One important MRI feature
      of FCD lesions is the blurring of the gray-white matter boundary (GWB),
      previously modelled by the gradient strength. However, in the absence of
      additional FCD descriptors, current gradient-based methods may yield false
      positives. Moreover, they do not explicitly quantify the level of blur which
      prevents from using them directly in the process of automated FCD detection. To
      improve the detection of FCD lesions displaying blur, we develop a novel
      algorithm called iterating local searches on neighborhood (ILSN). The novelty is
      that it measures the width of the blurry region rather than the gradient
      strength. The performance of our method is compared with the gradient magnitude
      method using precision and recall measures. The experimental results, tested on
      MRI data of 8 real FCD patients, indicate that our method has higher ability to
      correctly identify the FCD blurring than the gradient method. 

PMID- 25570702
TI  - Low-dose computed tomography image denoising based on joint wavelet and sparse
      representation.
AB  - Image denoising and signal enhancement are the most challenging issues in low
      dose computed tomography (CT) imaging. Sparse representational methods have shown
      initial promise for these applications. In this work we present a wavelet based
      sparse representation denoising technique utilizing dictionary learning and
      clustering. By using wavelets we extract the most suitable features in the images
      to obtain accurate dictionary atoms for the denoising algorithm. To achieve
      improved results we also lower the number of clusters which reduces computational
      complexity. In addition, a single image noise level estimation is developed to
      update the cluster centers in higher PSNRs. Our results along with the
      computational efficiency of the proposed algorithm clearly demonstrates the
      improvement of the proposed algorithm over other clustering based sparse
      representation (CSR) and K-SVD methods. 

PMID- 25570703
TI  - Robust estimation for class averaging in cryo-EM Single Particle Reconstruction.
AB  - Single Particle Reconstruction (SPR) for Cryogenic Electron Microscopy (cryo-EM)
      aligns and averages the images extracted from micrographs to improve the Signal
      to-Noise ratio (SNR). Outliers compromise the fidelity of the averaging. We
      propose a robust cross-correlation-like w-estimator for combating the effect of
      outliers on the average images in cryo-EM. The estimator accounts for the natural
      variation of signal contrast among the images and eliminates the need for a
      threshold for outlier rejection. We show that the influence function of our
      estimator is asymptotically bounded. Evaluations of the estimator on simulated
      and real cryo-EM images show good performance in the presence of outliers. 

PMID- 25570704
TI  - Objective measurement of erythema in psoriasis using digital color photography
      with color calibration.
AB  - Traditional metrics for evaluating the severity of psoriasis are highly
      subjective, which complicates efforts to identify effective treatments in
      clinical trials. We propose a method for the objective measurement of the
      psoriasis severity parameter of erythema (redness). This procedure is
      standardized for different camera systems and lighting environments through the
      usage of a color card with predetermined color values in order to calibrate the
      images. Quantitative measures based on the digital color images are shown to
      correlate well with subjective assessment of psoriasis severity collected using a
      standard numerical scale by a panel of dermatologists. Additionally, the color
      calibration process is shown to improve results. 

PMID- 25570705
TI  - Wireless Micro-Ball endoscopic image enhancement using histogram information.
AB  - Wireless endoscopy systems is a new innovative method widely used for
      gastrointestinal tract examination in recent decade. Wireless Micro-Ball
      endoscopy system with multiple image sensors is the newest proposed method which
      can make a full view image of the gastrointestinal tract. But still the quality
      of images from this new wireless endoscopy system is not satisfactory. It's hard
      for doctors and specialist to easily examine and interpret the captured images.
      The image features also are not distinct enough to be used for further
      processing. So as to enhance these low-contrast endoscopic images a new image
      enhancement method based on the endoscopic images features and color distribution
      is proposed in this work. The enhancement method is performed on three main steps
      namely color space transformation, edge preserving mask formation, and histogram
      information correction. The luminance component of CIE Lab, YCbCr, and HSV color
      space is enhanced in this method and then two other components added finally to
      form an enhanced color image. The experimental result clearly show the robustness
      of the method. 

PMID- 25570706
TI  - A new registration algorithm for estimating and discriminating average shapes of
      sets of corneal topographies.
AB  - In this study we present a method to build 3D corneal atlases of different
      populations using a registration step based on inter-surface volume minimization.
      First the construction method is presented. It is based on a global factor
      computation in order to minimize the volume between several surfaces. Then the
      significance of the choice of the matching step is shown with the comparison of
      two atlases expected to be nearly identical: male vs. female corneas. Finally two
      atlases are presented and compared, for two different populations: right myopic
      and hyperopic eyes. Our study demonstrates that the matching step is crucial to
      correctly compare two surfaces, and shows two clinical applications of this
      method. 

PMID- 25570707
TI  - Two-dimensional sample entropy analysis of rat sural nerve aging.
AB  - Entropy analysis of images are usually performed using Shannon entropy, which
      calculates the probability of occurrency of each gray level on the image.
      However, not only the pixel gray level but also the spatial distribution of
      pixels might be important for image analysis. On the other hand, sample entropy
      (SampEn) is an important tool for estimation of irregularity in time series,
      which calculates the probability of pattern occurrence within the series.
      Therefore, we propose here an extension of SampEn to a two-dimensional case,
      namely SampEn2D, as an entropy method for extracting features from images that
      accounts for the spatial distribution of pixels. SampEn2D was applied to
      histological segments of sural nerve obtained from young (30 days) and elderly
      (720 days) rats. Morphometric indexes, such as the total number of myelinated
      fibers and the average myelinated fibers area and perimeter were also calculated.
      Results show that SampEn2D can extract useful information from histological nerve
      images, classifying elderly rat image as more regular than young rat. As SampEn2D
      is related to irregularity/unpredictability, we can conclude that the proposed
      method is complementary to morphometric indexes. Further studies are being built
      to validate SampEn2D. 

PMID- 25570708
TI  - Physiological characterization of skin lesion using non-linear random forest
      regression model.
AB  - The current diagnostic technique for melanoma solely relies on the surface level
      of skin and under-skin information is neglected. Since physiological features of
      skin such as melanin are closely related to development of melanoma, the non
      linear physiological feature extraction model based on random forest regression
      is proposed. The proposed model characterizes the concentration of eumelanin and
      pheomelanin from standard camera images or dermoscopic images, which are
      conventionally used for diagnosis of melanoma. For the validation, the phantom
      study and the separability test using clinical images were conducted and compared
      against the state-of-the art non-linear and linear feature extraction models. The
      results showed that the proposed model outperformed other comparing models in
      phantom and clinical experiments. Promising results show that the quantitative
      characterization of skin features, which is provided by the proposed method, can
      allow dermatologists and clinicians to make a more accurate and improved
      diagnosis of melanoma. 

PMID- 25570710
TI  - Multiparametric MRI prostate cancer analysis via a hybrid morphological-textural
      model.
AB  - Multiparametric MRI has shown considerable promise as a diagnostic tool for
      prostate cancer grading. Diffusion-weighted MRI (DWI) has shown particularly
      strong potential for improving the delineation between cancerous and healthy
      tissue in the prostate gland. Current automated diagnostic methods using
      multiparametric MRI, however, tend to either use low-level features, which are
      difficult to interpret by radiologists and clinicians, or use highly subjective
      heuristic methods. We propose a novel strategy comprising a tumor candidate
      identification scheme and a hybrid textural-morphological feature model for
      delineating between cancerous and non-cancerous tumor candidates in the prostate
      gland via multiparametric MRI. Experimental results using clinical
      multiparametric MRI datasets show that the proposed strategy has strong potential
      as a diagnostic tool to aid radiologists and clinicians identify and detect
      prostate cancer more efficiently and effectively. 

PMID- 25570709
TI  - Fully automated localization of multiple pelvic bone structures on MRI.
AB  - In this paper, we present a fully automated localization method for multiple
      pelvic bone structures on magnetic resonance images (MRI). Pelvic bone structures
      are currently identified manually on MRI to identify reference points for
      measurement and evaluation of pelvic organ prolapse (POP). Given that this is a
      time-consuming and subjective procedure, there is a need to localize pelvic bone
      structures without any user interaction. However, bone structures are not easily
      differentiable from soft tissue on MRI as their pixel intensities tend to be very
      similar. In this research, we present a model that automatically identifies the
      bounding boxes of the bone structures on MRI using support vector machines (SVM)
      based classification and non-linear regression model that captures global and
      local information. Based on the relative locations of pelvic bones and organs,
      and local information such as texture features, the model identifies the location
      of the pelvic bone structures by establishing the association between their
      locations. Results show that the proposed method is able to locate the bone
      structures of interest accurately. The pubic bone, sacral promontory, and coccyx
      were correctly detected (DSI > 0.75) in 92%, 90%, and 88% of the testing images.
      This research aims to enable accurate, consistent and fully automated
      identification of pelvic bone structures on MRI to facilitate and improve the
      diagnosis of female pelvic organ prolapse. 

PMID- 25570711
TI  - Investigating local spatially-enhanced structural and textural descriptors for
      classification of iPSC colony images.
AB  - Induced pluripotent stem cells (iPSC) can be derived from fully differentiated
      cells of adult individuals and used to obtain any other cell type of the human
      body. This implies numerous prospective applications of iPSCs in regenerative
      medicine and drug development. In order to obtain valid cell culture, a quality
      control process must be applied to identify and discard abnormal iPSC colonies.
      Computer vision systems that analyze visual characteristics of iPSC colony health
      can be especially useful in automating and improving the quality control process.
      In this paper, we present an ongoing research that aims at the development of
      local spatially-enhanced descriptors for classification of iPSC colony images.
      For this, local oriented edges and local binary patterns are extracted from the
      detected colony regions and used to represent structural and textural properties
      of the colonies, respectively. We preliminary tested the proposed descriptors in
      classifying iPSCs colonies according to the degree of colony abnormality. The
      tests showed promising results for both, detection of iPSC colony borders and
      colony classification. 

PMID- 25570712
TI  - Sparse kernel entropy component analysis for dimensionality reduction of
      neuroimaging data.
AB  - The neuroimaging data typically has extremely high dimensions. Therefore,
      dimensionality reduction is commonly used to extract discriminative features.
      Kernel entropy component analysis (KECA) is a newly developed data transformation
      method, where the key idea is to preserve the most estimated Renyi entropy of the
      input space data set via a kernel-based estimator. Despite its good performance,
      KECA still suffers from the problem of low computational efficiency for large
      scale data. In this paper, we proposed a sparse KECA (SKECA) algorithm with the
      recursive divide-and-conquer based solution, and then applied it to perform
      dimensionality reduction of neuroimaging data for classification of the
      Alzheimer's disease (AD). We compared the SKECA with KECA, principal component
      analysis (PCA), kernel PCA (KPCA) and sparse KPCA. The experimental results
      indicate that the proposed SKECA has most superior performance to all other
      algorithms when extracting discriminative features from neuroimaging data for AD
      classification. 

PMID- 25570713
TI  - On generating cell exemplars for detection of mitotic cells in breast cancer
      histopathology images.
AB  - Mitotic activity is one of the main criteria that pathologists use to decide the
      grade of the cancer. Computerised mitotic cell detection promises to bring
      efficiency and accuracy into the grading process. However, detection and
      classification of mitotic cells in breast cancer histopathology images is a
      challenging task because of the large intra-class variation in the visual
      appearance of mitotic cells in various stages of cell division life cycle. In
      this paper, we test the hypothesis that cells in histopathology images can be
      effectively represented using cell exemplars derived from sub-images of various
      kinds of cells in an image for the purposes of mitotic cell classification. We
      compare three methods for generating exemplar cells. The methods have been
      evaluated in terms of classification performance on the MITOS dataset. The
      experimental results demonstrate that eigencells combined with support vector
      machines produce reasonably high detection accuracy among all the methods.

PMID- 25570714
TI  - Morphological and textural analysis of centroblasts in low-thickness sliced
      tissue biopsies of follicular lymphoma.
AB  - This paper presents a new method for discriminating centroblast (CB) from non
      centroblast cells in microscopic images acquired from tissue biopsies of
      follicular lymphoma. In the proposed method tissue sections are sliced at a low
      thickness level, around 1-1.5 MUm, which provides a more detailed depiction of
      the nuclei and other textural information of cells usually not distinguishable in
      thicker specimens, such as 4-5 MUm, that have been used in the past by other
      researchers. To identify CBs, a morphological and textural analysis is applied in
      order to extract various features related to their nuclei, nucleoli and
      cytoplasm. The generated feature vector is then used as input in a two-class SVM
      classifier with epsilon-Support Vector Regression and radial basis kernel
      function. Experimental results with an annotated dataset consisting of 300 images
      of centroblasts and non-centroblasts, derived from high-power field images of
      follicular lymphoma stained with Hematoxylin and Eosin, have shown the great
      potential of the proposed method with an average detection rate of 97.44%.

PMID- 25570715
TI  - Multi-classification of cell deformation based on object alignment and run length
      statistic.
AB  - Cellular morphology is widely applied in digital pathology and is essential for
      improving our understanding of the basic physiological processes of organisms.
      One of the main issues of application is to develop efficient methods for cell
      deformation measurement. We propose an innovative indirect approach to analyze
      dynamic cell morphology in image sequences. The proposed approach considers both
      the cellular shape change and cytoplasm variation, and takes each frame in the
      image sequence into account. The cell deformation is measured by the minimum
      energy function of object alignment, which is invariant to object pose. Then an
      indirect analysis strategy is employed to overcome the limitation of gradual
      deformation by run length statistic. We demonstrate the power of the proposed
      approach with one application: multi-classification of cell deformation.
      Experimental results show that the proposed method is sensitive to the morphology
      variation and performs better than standard shape representation methods. 

PMID- 25570716
TI  - Development and preliminary evaluation of an Android based heart rate variability
      biofeedback system.
AB  - The reduced Heart Rate Variability (HRV) is believed to be associated with
      several diseases such as congestive heart failure, diabetes and chronic kidney
      diseases (CKD). In these cases, HRV biofeedback may be a potential intervention
      method to increase HRV which in turn is beneficial to these patients. In this
      work, a real-time Android biofeedback application based on a Bluetooth enabled
      ECG and thoracic electrical bioimpedance (respiration) measurement device has
      been developed. The system performance and usability have been evaluated in a
      brief study with eight healthy volunteers. The result demonstrates real-time
      performance of system and positive effects of biofeedback training session by
      increased HRV and reduced heart rate. Further development of the application and
      training protocol is ongoing to investigate duration of training session to find
      an optimum length and interval of biofeedback sessions to use in potential
      interventions. 

PMID- 25570717
TI  - Classification of acute stress using linear and non-linear heart rate variability
      analysis derived from sternal ECG.
AB  - Chronic stress detection is an important factor in predicting and reducing the
      risk of cardiovascular disease. This work is a pilot study with a focus on
      developing a method for detecting short-term psychophysiological changes through
      heart rate variability (HRV) features. The purpose of this pilot study is to
      establish and to gain insight on a set of features that could be used to detect
      psychophysiological changes that occur during chronic stress. This study elicited
      four different types of arousal by images, sounds, mental tasks and rest, and
      classified them using linear and non-linear HRV features from electrocardiograms
      (ECG) acquired by the wireless wearable ePatch(r) recorder. The highest
      recognition rates were acquired for the neutral stage (90%), the acute stress
      stage (80%) and the baseline stage (80%) by sample entropy, detrended fluctuation
      analysis and normalized high frequency features. Standardizing non-linear HRV
      features for each subject was found to be an important factor for the improvement
      of the classification results. 

PMID- 25570718
TI  - On heart rate regulation in cycle-ergometer exercise.
AB  - In this paper, we have focused on the issue of regulating the human heart rate
      (HR) to a predefined reference trajectory, especially for cycle-ergometer
      exercise used for training or rehabilitation. As measuring HR is relatively easy
      compared to exercise intensity, it has been used in the wide range of training
      programs. The aim of this paper is to develop a non-model-based control strategy
      using proportional, integral and derivative (PID) controller/relay controller to
      regulate the HR to track a desired trajectory. In the case of using PID
      controller, the controller output signal is interpreted as a voice or auditory
      command, referred to as biofeedback, which can be heard by the exercising subject
      as a part of the control-loop. Alternatively, the relay controller output signals
      can be converted to some special words which can be recognised by the exerciser.
      However, in both cases, to effectively communicate to the user a change in
      exercise intensity, the timing of this feedback signal relative to the positions
      of the pedals becomes quite critical. A feedback signal delivered when the pedals
      are not in a suitable position to efficiently exert force may be ineffective and
      may lead to a cognitive disengagement of the user form the feedback controller.
      In this paper we examine the need and the consequence of synchronising the
      delivery of the feedback signal with an optimal and user specific placement of
      the pedal. 

PMID- 25570719
TI  - Sternal pulse rate variability compared with heart rate variability on healthy
      subjects.
AB  - The heart rate variability (HRV) is a commonly used method to quantify the
      sympathetic and the parasympathetic modulation of the heart rate. HRV is mainly
      conducted on electrocardiograms (ECG). However, the use of photo-plethysmography
      (PPG) as a marker of the autonomic tone is emerging. In this study we
      investigated the feasibility of deriving pulse rate variability (PRV) using PPG
      signals recorded by a reflectance PPG sensor attached to the chest bone (sternum)
      and comparing it to HRV. The recordings were conducted on 9 healthy subjects
      being in a relaxed supine position and under forced respiration, where the
      subjects were asked to breathe following a visual scale with a rate of 27
      breaths/min. HRV parameters such as the mean intervals (meanNN), the standard
      deviation of intervals (SDNN), the root mean square of difference of successive
      intervals (RMSSD), and the proportion of intervals differing more than 50 ms
      (pNN50) were calculated from the R peak-to-R peak (R-R) and pulse-to-pulse (P-P)
      intervals. In the frequency domain the low and high frequency ratio of the power
      spectral density (LF/HF) was also computed. The Pearson correlation coefficient
      showed significant correlation for all the parameters (r > 0.95 with p < 0.001)
      and the Bland-Altmann analysis showed close agreement between the two methods for
      all the parameters during resting and forced respiration condition. Thus, PRV
      analysis using sternal PPG can be an alternative to HRV analysis on healthy
      subjects at.

PMID- 25570720
TI  - The matching of sinus arrhythmia to respiration: are trauma patients without
      serious injury comparable to healthy laboratory subjects?
AB  - We sought to better understand the physiology underlying the metrics of heart
      rate variability (HRV) in trauma patients without serious injury, compared to
      healthy laboratory controls. In trauma patients without serious injury (110
      subjects, 470 2-min data segments), we studied the correlation between sinus
      arrhythmia (SA) rate, heart rate (HR), and respiratory rate (RR). Most segments
      with 2.4 < HR/RR < 4.8 exhibited SA-RR matching, whereas rate matching was absent
      in 81% of the segments with HR/RR < 2.4 and in 86% of the segments with HR/RR >
      4.8. The findings were comparable, in some cases remarkably so, to previous
      reports from healthy laboratory subjects. The presence (or absence) of SA-RR
      matching, when SA is largely controlled by respiration, can be anticipated in
      this trauma population. This work provides a valuable step towards the definition
      of patterns of HRV found in trauma patients with and without life-threatening
      injury.

PMID- 25570721
TI  - Gender differences in cardiovascular and cardiorespiratory coupling in healthy
      subjects during head-up tilt test by Joint Symbolic Dynamics.
AB  - Gender related-differences in the autonomic regulation of the cardiovascular and
      cardiorespiratory systems have been studied mainly by hemodynamic responses
      during different physical stressors. In this study, the influence of gender on
      the autonomic response to an orthostatic challenge was investigated by obtaining
      the cardiovascular and cardiorespiratory coupling using the nonlinear technique
      known as joint symbolic dynamics (JSD) representation. This study includes 24
      healthy young subjects. Males (N=12) and age-matched females (N=12) were enrolled
      in a head-up tilt (HUT) test, breathing normally, including 5 minutes of supine
      position (baseline) and 25-40 minutes of 70 degrees  orthostatic phase. The
      cardiovascular and cardiorespiratory couplings were obtained at baseline, early
      and middle orthostatic phases. Although in baseline there were some gender
      differences, parameters from JSD showed highly significant (p=0.0004) differences
      in specific cardiovascular coupling patterns in the early tilt phase.
      Furthermore, JSD analysis revealed that in males, due to increased sympathetic
      activity, exist a lower degree of cardiovascular coupling accompanied with an
      increased occurrence of tachycardic patterns. On the other hand, the
      cardiorespiratory coupling revealed only very few slightly significant
      differences in all three phases. 

PMID- 25570722
TI  - The impact of cervical manipulation on heart rate variability.
AB  - Heart Rate variability (HRV) is the inter-beat variability in heart rate and is
      moderated by the balance of sympathetic and parasympathetic divisions of the
      autonomic nervous system. Electrocardiography (ECG) can be utilized to obtain Low
      frequency (LF) to high frequency (HF) ratios that represent sympathetic to
      parasympathetic response, respectively and these ratios may be increased in
      people with chronic pain. Spinal manipulation is often used to manage
      musculoskeletal disorders such as neck pain. This study assesses the influence of
      cervical manipulation on HRV using LF/HF ratio. Ten subjects without neck pain
      formed the control condition and passive head movement (PHM) condition during
      which their head was flexed, extended and rotated. Ten subjects with subclinical
      neck pain underwent the same conditions. A separate session was performed for an
      actual manipulation. LabChartTM software was utilized to collect and analyze five
      minute pre and post R-R intervals. Repeated measures of ANOVA demonstrated
      significant interaction effect on HRV (F (1, 18) = 6.841, p = 0.018) following
      manipulation vs. PHM. Subsequent analysis showed a significant decrease in the
      ratio during manipulation condition (p = 0.0316), that was not seen in any other
      conditions, suggesting a significant autonomic nervous system alteration. This
      study may lead to new techniques to assess the effectiveness of various treatment
      interventions.

PMID- 25570723
TI  - Estimation of respiratory impedance at low frequencies during spontaneous
      breathing using the forced oscillation technique.
AB  - The forced oscillation technique (FOT) is a non-invasive method to measure the
      respiratory impedance Z, defined as the complex ratio of transrespiratory
      pressure P to the airflow at the airway opening Q as a function of frequency. FOT
      determines Z by superimposing small amplitude pressure oscillations on the normal
      breathing and measuring the resulting air flow. In this work a new approach for
      the analysis of the respiratory impedance Z at low frequencies (0.1-5 Hz) during
      spontaneous breathing is presented. When the respiratory impedance is measured in
      frequency ranges that overlap with the frequency of spontaneous breathing (0.1-1
      Hz), the measured air flow will contain both the breathing of the patient and the
      response of the respiratory impedance to the pressure oscillations. A nonlinear
      estimator is developed which is able to separate the breathing signal from the
      respiratory response in order to obtain the respiratory impedance. The estimated
      results are used to obtain accurate estimates of airway and tissue components of
      a constant phase model. 

PMID- 25570724
TI  - Basic study on the most relaxing respiration period in children to aid the
      development of a respiration-leading stuffed toy.
AB  - Following natural disasters, accidents, and shocking incidents, some children
      experience post-traumatic stress disorder (PTSD). The respiration control method,
      which relaxes the body and mind, may efficiently prevent PTSD. Therefore, we
      developed a stuffed toy that leads children's respiration using the up-and-down
      movement of the abdomen to help them relax. We investigated the most appropriate
      respiration period for children's relaxation. Data from studies on heart rate
      variability (HRV) biofeedback training suggest that breathing at the respiration
      period at which HRV is the highest is effective for improving chronic diseases.
      Therefore, we measured the relationship between the respiration period and
      physiological indices, including HRV. The participants were 10 children aged 5-12
      years. HRV was the highest at a 10-12-s respiration period in all 10 children.
      However, the most suitable respiration period for smooth breathing and relaxation
      was different from that at which HRV is the highest. Therefore, the most relaxing
      respiration periods for children need to be determined by indices other than HRV.

PMID- 25570725
TI  - Evaluation of the use of frequency response in the diagnosis of pleural effusion
      on a phantom model of the human lungs.
AB  - Pleural effusion is one of the most widespread respiratory diseases in the world.
      Current diagnostic techniques include a combination of medical history and x-ray
      or CT scan imaging of the chest. However, these techniques are expensive and
      impractical in resource limited settings. We propose a new method based on sound
      transmission into the respiratory system through the chest wall. To evaluate this
      technique, a sine sweep signal with a frequency range between 100 Hz and 1000 Hz
      was transmitted into a phantom model of the human lungs capable of simulating
      healthy and effused conditions. The frequency response of the model under both
      conditions was computed and compared to evaluate the diagnostic performance of
      the new method. The results indicate that there is a significant difference
      between the frequency response of healthy and effused lungs, which suggests that
      the new technique may be suitable for the clinical diagnosis of pleural effusion.

PMID- 25570726
TI  - Analysis of the breathing pattern in elderly patients using the Hurst exponent
      applied to the respiratory flow signal.
AB  - Due to the increasing elderly population and the extensive number of
      comorbidities that affect them, studies are required to determine future
      increments in admission to emergency departments. Some of these studies could
      focus on the relation between chronic diseases and breathing pattern in elderly
      patients. Variations in the fractal properties of respiratory signals can be
      associated with several diseases. To determine the relationship between these
      variations and breathing patterns, and to quantify the fractal properties of
      respiratory flow signals, we estimated the Hurst exponent (H). Detrended
      fluctuation analysis (DFA) and discrete wavelet transform-based estimation (DWTE)
      methods were applied. The estimation methods were analyzed using simulated data
      series generated by fractional Gaussian noise. 43 elderly patients (19 patients
      with a non-periodic breathing pattern - nPB, and 24 patients with a periodic
      breathing pattern - PB) were studied. The results were evaluated according to the
      length of data and the number of averaged data series used to obtain a good
      estimation. The DWTE method estimated the respiratory flow signals better than
      the DFA method, and obtained Hurst values clustered by group. We found
      significant differences in the H exponent (p = 0.002) between PB and nPB
      patients, which showed different behavior in the fractal properties. 

PMID- 25570727
TI  - Correcting hypothalamic-pituitary-adrenal axis dysfunction using observer-based
      explicit nonlinear model predictive control.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is critical in maintaining
      homeostasis under physical and psychological stress by modulating cortisol levels
      in the body. Dysregulation of cortisol levels is linked to numerous stress
      related disorders. In this paper, an automated treatment methodology is proposed,
      employing a variant of nonlinear model predictive control (NMPC), called explicit
      MPC (EMPC). The controller is informed by an unknown input observer (UIO), which
      estimates various hormonal levels in the HPA axis system in conjunction with the
      magnitude of the stress applied on the body, based on measured concentrations of
      adreno-corticotropic hormones (ACTH). The proposed closed-loop control strategy
      is tested on multiple in silico patients and the effectiveness of the controller
      performance is demonstrated. 

PMID- 25570728
TI  - Classification of serous ovarian tumors based on microarray data using
      multicategory support vector machines.
AB  - Ovarian cancer, the most fatal of reproductive cancers, is the fifth leading
      cause of death in women in the United States. Serous borderline ovarian tumors
      (SBOTs) are considered to be earlier or less malignant forms of serous ovarian
      carcinomas (SOCs). SBOTs are asymptomatic and progression to advanced stages is
      common. Using DNA microarray technology, we designed multicategory classification
      models to discriminate ovarian cancer subclasses. To develop multicategory
      classification models with optimal parameters and features, we systematically
      evaluated three machine learning algorithms and three feature selection methods
      using five-fold cross validation and a grid search. The study included 22
      subjects with normal ovarian surface epithelial cells, 12 with SBOTs, and 79 with
      SOCs according to microarray data with 54,675 probe sets obtained from the
      National Center for Biotechnology Information gene expression omnibus repository.
      Application of the optimal model of support vector machines one-versus-rest with
      signal-to-noise as a feature selection method gave an accuracy of 97.3%, relative
      classifier information of 0.916, and a kappa index of 0.941. In addition, 5
      features, including the expression of putative biomarkers SNTN and AOX1, were
      selected to differentiate between normal, SBOT, and SOC groups. An accurate
      diagnosis of ovarian tumor subclasses by application of multicategory machine
      learning would be cost-effective and simple to perform, and would ensure more
      effective subclass-targeted therapy. 

PMID- 25570730
TI  - An early respiratory distress detection method with Markov models.
AB  - A method for early detection of respiratory distress in hospitalized patients
      which is based on a multi-parametric analysis of respiration rate (RR) and pulse
      oximetry (SpO2) data trends to ascertain patterns of patient instability
      pertaining to respiratory distress is described. Current practices of triggering
      caregiver alerts are based on simple numeric threshold breaches of SpO2. The
      pathophysiological patterns of respiratory distress leading to in-hospital deaths
      are much more complex to be detected by numeric thresholds. Our pattern detection
      algorithm is based on a Markov model framework based on multi-parameter
      pathophysiological patterns of respiratory distress, and triggers in a timely
      manner and prior to the violation of SpO2 85-90% threshold, providing additional
      lead time to attempt to reverse the deteriorating state of the patient. We
      present the performance of the algorithm on MIMIC II dataset resulting in true
      positive rate of 92% and false positive rate of 6%. 

PMID- 25570729
TI  - Identifying homogenous subgroups for individual patient meta-analysis based on
      Rough Set Theory.
AB  - Failure to detect and manage heterogeneity between clinical trials included in
      meta-analysis may lead to misinterpretation of summary effect estimates. This may
      ultimately compromise the validity of the results of the meta-analysis.
      Typically, when heterogeneity between trials is detected, researchers use
      sensitivity or subgroup analysis to manage it. However, both methods fail to
      explain why heterogeneity existed in the first place. Here we propose a novel
      methodology that relies on Rough Set Theory (RST) to detect, explain, and manage
      the sources of heterogeneity applicable to meta-analysis performed on individual
      patient data (IPD). The method exploits the RST relations of discernibility and
      indiscernibility to create homogeneous groups of patients. We applied our
      methodology on a dataset of 1,111 patients enrolled in 9 randomized controlled
      trials studying the effect of two transplantation procedures in the management of
      hematologic malignancies. Our method was able to create three subgroups of
      patients with remarkably low statistical heterogeneity values (16.8%, 0% and 0%
      respectively). The proposed methodology has the potential to automatize and
      standardize the process of detecting and managing heterogeneity in IPD meta
      analysis. Future work involves investigating the applications of the proposed
      methodology in analyzing treatment effects in patients belonging to different
      risk groups, which will ultimately assist in personalized healthcare decision
      making. 

PMID- 25570731
TI  - Mathematical models for absorption and efficacy of ovarian cancer treatments.
AB  - The creation of personal and individualized anti-cancer treatments has been a
      major goal in the progression of cancer discovery as evident by the continuous
      research efforts in genetics and population based PK/PD studies. In this paper we
      use our clinical decision support tool, called ChemoDSS, to evaluate the
      effectiveness of three treatments recommended by the NCCN guidelines for ovarian
      cancer using pre-clinical data from the literature. In particular, we analyze the
      treatments of PC (i.e., Paclitaxel and Cispaltin), DC (i.e., Docetaxel and
      Carboplatin), and PBC (i.e., Paclitaxel, Bevacizumab, and Carboplatin). Our in
      silico analysis of the ovarian cancer treatments shows that PC was the most
      effective regimen for treating ovarian cancer compared to DC and PBC, which is
      consistent with literature findings. We demonstrate that we can successfully
      evaluate the effectiveness of the selected ovarian cancer treatment regimens
      using ChemoDSS. 

PMID- 25570732
TI  - Deformable image tracking of the parotid gland for adaptive radiotherapy
      application.
AB  - Radiation therapy is a type of cancer treatment using radiation at different
      times defined as treatment sessions, distributed over different weeks. In each
      session, we have to determine and define the optimal treatment parameters for the
      patient. The aim of Adaptive Radiotherapy Treatment (ART) is to identify any
      change of initial parameters during the treatment course and modify the treatment
      plan for the purpose of maintaining optimal treatment objectives. In order to
      track the deformable image of biological organ such as the parotid gland, a 3D
      reconstruction is needed. 10 patients were scanned at the medical center of Oscar
      Lambret (Lille, France) using CT scan as imaging modality. The contours of the
      acquired images were extracted manually by the expert. Relaxed bi-cubic Bezier
      spline surface has been used in our study for the purpose of automatically
      reconstruction of the biological organ. Once the reconstruction is accomplished,
      the volume of the parotid gland at each session of treatment has been calculated
      for each patient. The obtained results show a decreasing of the volume of the
      parotid from one week to other one and a shifting of the detected center of
      gravity. These variations should be used to build a predictive model for adaptive
      robotized radiotherapy. 

PMID- 25570733
TI  - Biomarkers from biosimulations: Transcriptome-To-ReactomeTM Technology for
      individualized medicine.
AB  - We validated a model of the TGF-beta signaling pathway using reactions from
      Reactome. Using a patentpending technique, gene expression profiles from
      individual patients are used to determine model parameters. Gene expression
      profiles from 45 women, normal, or benign tumor and malignant breast cancer were
      used as training and validating sets for assessing clinical sensitivity and
      specificity. Biomarkers were identified from the biosimulation results using
      sensitivity analyses and derivative properties from the model. A membrane
      signaling marker had sensitivity of 80% and specificity of 60%; while a nuclear
      transcription factor marker had sensitivity of 80% and specificity of 90% to
      predict malignancy. Use of Fagan's nomogram increased probability from 7.5% for
      positive mammogram to 39% with positive results of the biosimulation for the
      nuclear marker. Our technology will allow researchers to identify and develop
      biomarkers and assist clinicians in diagnostic and treatment decision making. 

PMID- 25570734
TI  - Hemodynamic-impact-based prioritization of ventricular tachycardia alarms.
AB  - Ventricular tachycardia (V-tach) is a very serious condition that occurs when the
      ventricles are driven at high rates. The abnormal excitation pathways make
      ventricular contraction less synchronous resulting in less effective filling and
      emptying of the left ventricles. However, almost half of the V-tach alarms
      declared through processing of patterns observed in electrocardiography are not
      clinically actionable. The focus of this study is to provide guidance on
      determining whether a technically-correct V-tach alarm is clinically-actionable
      by determining its "hemodynamic impact". A supervisory learning approach based on
      conditional inference trees to determine the hemodynamic impact of a V-tach alarm
      based on extracted features is described. According to preliminary results on a
      subset of Multiparameter intelligent monitoring in intensive care II (MIMIC-II)
      database, true positive rate of more than 90% can be achieved. 

PMID- 25570735
TI  - Multicategory classification of 11 neuromuscular diseases based on microarray
      data using support vector machine.
AB  - We applied multicategory machine learning methods to classify 11 neuromuscular
      disease groups and one control group based on microarray data. To develop
      multicategory classification models with optimal parameters and features, we
      performed a systematic evaluation of three machine learning algorithms and four
      feature selection methods using three-fold cross validation and a grid search.
      This study included 114 subjects of 11 neuromuscular diseases and 31 subjects of
      a control group using microarray data with 22,283 probe sets from the National
      Center for Biotechnology Information (NCBI). We obtained an accuracy of 100%,
      relative classifier information (RCI) of 1.0, and a kappa index of 1.0 by
      applying the models of support vector machines one-versus-one (SVM-OVO), SVM one
      versus-rest (OVR), and directed acyclic graph SVM (DAGSVM), using the ratio of
      genes between categories to within-category sums of squares (BW) feature
      selection method. Each of these three models selected only four features to
      categorize the 12 groups, resulting in a time-saving and cost-effective strategy
      for diagnosing neuromuscular diseases. In addition, a gene symbol, SPP1 was
      selected as the top-ranked gene by the BW method. We confirmed relationships
      between the gene (SPP1) and Duchenne muscular dystrophy (DMD) from a previous
      study. With our models as clinically helpful tools, neuromuscular diseases could
      be classified quickly using a computer, thereby giving a time-saving, cost
      effective, and accurate diagnosis. 

PMID- 25570736
TI  - Prediction of mortality from respiratory distress among long-term mechanically
      ventilated patients.
AB  - With the advent of inexpensive storage, pervasive networking, and wireless
      devices, it is now possible to store a large proportion of the medical data that
      is collected in the intensive care unit (ICU). These data sets can be used as
      valuable resources for developing and validating predictive analytics. In this
      report, we focus on the problem of prediction of mortality from respiratory
      distress among long-term mechanically ventilated patients using data from the
      publicly-available MIMIC-II database. Rather than only reporting p-values for
      univariate or multivariate regression, as in previous work, we seek to generate
      sparsest possible model that will predict mortality. We find that the presence of
      severe sepsis is highly associated with mortality. We also find that variables
      related to respiration rate have more predictive accuracy than variables related
      to oxygenation status. Ultimately, we have developed a model which predicts
      mortality from respiratory distress in the ICU with a cross-validated area-under
      the-curve (AUC) of approximately 0.74. Four methodologies are utilized for model
      dimensionality-reduction: univariate logistic regression, multivariate logistic
      regression, decision trees, and penalized logistic regression. 

PMID- 25570737
TI  - Prototype early warning system for heart disease detection using Android
      Application.
AB  - Heart Disease affects approximately 70 million people worldwide where most people
      do not even know the symptoms. This research examines the prototype of early
      warning system for heart disease by android application. It aims to facilitate
      users to early detect heart disease which can be used independently. To build the
      application in android phone, variable centered intelligence rule system (VCIRS)
      as decision makers and pulse sensor - Arduino as heart rate detector were applied
      in this study. Moreover, in Arduino, the heart rate will become an input for
      symptoms in Android Application. The output of this system is the conclusion
      statement of users diagnosed with either coronary heart disease, hypertension
      heart disease, rheumatic heart disease or do not get any kind of heart disease.
      The result of diagnosis followed by analysis of the value of usage variable rate
      (VUR) rule usage rate (RUR) and node usage rate (NUR) that shows the value of the
      rule that will increase when the symptoms frequently appear. This application was
      compared with the medical analysis from 35 cases of heart disease and it showed
      concordance between diagnosis from android application and expert diagnosis of
      the doctors. 

PMID- 25570738
TI  - Development of a system for telemonitoring of respiration parameters for patients
      with Obstructive Sleep Apnea.
AB  - Obstructive Sleep Apnea is a chronic sleep disorder affecting a large number of
      the global population. Telemonitoring has been successfully evaluated as an
      alternative method to traditional care. This paper identifies drawbacks of the
      current telemonitoring approaches and presents a universal wireless system for
      continuous monitoring of basic respiration parameters. The proposed system
      monitors four parameters, namely respiratory flow, airway pressure, Carbon
      Dioxide (CO2) and Oxygen (O2) gas concentrations. Data are wirelessly transmitted
      to a computer which acts as a web server. The system will allow remote evaluation
      of home ventilation support efficiency and the application of custom algorithms
      for decision support and respiration event detection. 

PMID- 25570739
TI  - Development of UV-ionization based trace differential mobility sensor for acetone
      and hexane.
AB  - Clinical studies in recent times confirm feasibility of using trace
      concentrations of volatile organic compounds (VOC) in human exhale air as
      potential bio-markers for a variety of disease states. A Differential Mobility
      Sensor (DMS) with dual ultra-violet (UV) photo-ionization source is proposed and
      demonstrated for measurement of trace amounts of VOC gases in human exhale air.
      Experimental work performed with the DMS using high frequency asymmetrical
      waveform field for detection of trace concentrations of acetone and hexane with a
      few carrier gases including air, CO2 and O2 is discussed. The detection limit as
      estimated for Signal to Noise Ratio (SNR) of 3 is of the order of sub ppm levels
      for acetone and hexane. Experimental studies clearly demonstrate selective
      sensing of a gas in a mixture of gases by applying appropriate compensation
      field. Preliminary study on sensing of acetone in human breath shows good a
      correlation with blood glucose measurements. 

PMID- 25570740
TI  - An alternating pressure sequence proposal for an air-cell cushion for preventing
      pressure ulcers.
AB  - The distribution and release of pressure on ischial regions are two important
      parameters for evaluating the effectiveness of a cushion; especially the release
      of pressure over time on ischial tuberosities, which is significant for
      preventing pressure ulcers. The aim of this work is to evaluate the effect on
      interface pressure through the application of a proposed alternating pressure
      sequence for an air-cell cushion. Six healthy volunteers were asked to sit on the
      air cell cushion, in static and alternating modes, as well as on a typical foam
      cushion for 12 minutes. Interface pressure was monitored with a matrix sensor
      system. Interface pressure values on ischial tuberosities, user contact area and
      pressure distribution were analyzed. Results showed that IP on IT tends to
      increase in both foam and static cushions, while in alternating cushion IP on IT
      tends to decrease. User contact area was significantly larger in alternating
      cushion than in static or foam cushions. Moreover, there is a better pressure re
      distribution with alternating cushion than with the other cushions. The goal of
      the alternating sequence is to redistribute pressure and stimulate the ischial
      regions in order to promote blood flow and prevent pressure occurring in
      wheelchair users. 

PMID- 25570741
TI  - A multifactorial falls risk prediction model for hospitalized older adults.
AB  - Ageing population worldwide has grown fast with more cases of chronic illnesses
      and co-morbidity, involving higher healthcare costs. Falls are one of the leading
      causes of unintentional injury-related deaths in older adults. The aim of this
      study was to develop a robust multifactorial model toward the falls risk
      prediction. The proposed model employs real-time vital signs, motion data, falls
      history and muscle strength. Moreover, it identifies high-risk individuals for
      the development falls in their activity of daily living (ADL). The falls risk
      prediction model has been tested at a controlled-environment in hospital with 30
      patients and compared with the results from the Morse fall scale. The simulated
      results show the proposed algorithm achieved an accuracy of 98%, sensitivity of
      96% and specificity of 100% among a total of 80 intentional falls and 40 ADLs.
      The ultimate aim of this study is to extend the application to elderly home care
      and monitoring. 

PMID- 25570742
TI  - New roles & responsibilities of hospital biomedical engineering.
AB  - Over the last decade the changing healthcare environment has required hospitals
      and specifically Biomedical Engineering to critically evaluate, optimize and
      adapt their operations. The focus is now on new technologies, changes to the
      environment of care, support requirements and financial constraints. Memorial
      Sloan Kettering Cancer Center (MSKCC), an NIH-designated comprehensive cancer
      center, has been transitioning to an increasing outpatient care environment. This
      transition is driving an increase in-patient acuity coupled with the need for
      added urgency of support and response time. New technologies, regulatory
      requirements and financial constraints have impacted operating budgets and in
      some cases, resulted in a reduction in staffing. Specific initiatives, such as
      the Joint Commission's National Patient Safety Goals, requirements for an
      electronic medical record, meaningful use and ICD10 have caused institutions to
      reevaluate their operations and processes including requiring Biomedical
      Engineering to manage new technologies, integrations and changes in the
      electromagnetic environment, while optimizing operational workflow and resource
      utilization. This paper addresses the new and expanding responsibilities and
      approach of Biomedical Engineering organizations, specifically at MSKCC. It is
      suggested that our experience may be a template for other organizations facing
      similar problems. Increasing support is necessary for Medical Software - Medical
      Device Data Systems in the evolving wireless environment, including RTLS and
      RFID. It will be necessary to evaluate the potential impact on the growing
      electromagnetic environment, on connectivity resulting in the need for dynamic
      and interactive testing and the growing demand to establish new and needed
      operational synergies with Information Technology operations and other
      operational groups within the institution, such as nursing, facilities
      management, central supply, and the user departments. 

PMID- 25570743
TI  - Automatic measurement of physical mobility in Get-Up-and-Go Test using Kinect
      sensor.
AB  - Get-Up-and-Go Test is commonly used for assessing the physical mobility of the
      elderly by physicians. This paper presents a method for automatic analysis and
      classification of human gait in the Get-Up-and-Go Test using a Microsoft Kinect
      sensor. Two types of features are automatically extracted from the human skeleton
      data provided by the Kinect sensor. The first type of feature is related to the
      human gait (e.g., number of steps, step duration, and turning duration); whereas
      the other one describes the anatomical configuration (e.g., knee angles, leg
      angle, and distance between elbows). These features characterize the degree of
      human physical mobility. State-of-the-art machine learning algorithms (i.e. Bag
      of Words and Support Vector Machines) are used to classify the severity of gaits
      in 12 subjects with ages ranging between 65 and 90 enrolled in a pilot study. Our
      experimental results show that these features can discriminate between patients
      who have a high risk for falling and patients with a lower fall risk. 

PMID- 25570744
TI  - A wearable system for measuring limb movements and balance control abilities
      based on a modular and low-cost inertial unit.
AB  - Monitoring balance and movement has proven useful in many applications ranging
      from fall risk assessment, to quantifying exercise, studying people habits and
      monitoring the elderly. Here we present a versatile, wearable instrument capable
      of providing objective measurements of limb movements for the assessment of motor
      and balance control abilities. The proposed device allows measuring linear
      accelerations, angular velocities and heading either online, through wireless
      connection to a computer, or for long-term monitoring, thanks to its local
      storage abilities. One or more body parts may be simultaneously monitored in a
      single or multiple sensors configuration. 

PMID- 25570745
TI  - Affordable, automatic quantitative fall risk assessment based on clinical balance
      scales and Kinect data.
AB  - The problem of a correct fall risk assessment is becoming more and more critical
      with the ageing of the population. In spite of the available approaches allowing
      a quantitative analysis of the human movement control system's performance, the
      clinical assessment and diagnostic approach to fall risk assessment still relies
      mostly on non-quantitative exams, such as clinical scales. This work documents
      our current effort to develop a novel method to assess balance control abilities
      through a system implementing an automatic evaluation of exercises drawn from
      balance assessment scales. Our aim is to overcome the classical limits
      characterizing these scales i.e. limited granularity and inter-/intra-examiner
      reliability, to obtain objective scores and more detailed information allowing to
      predict fall risk. We used Microsoft Kinect to record subjects' movements while
      performing challenging exercises drawn from clinical balance scales. We then
      computed a set of parameters quantifying the execution of the exercises and fed
      them to a supervised classifier to perform a classification based on the clinical
      score. We obtained a good accuracy (~82%) and especially a high sensitivity
      (~83%). 

PMID- 25570746
TI  - Hospital-based expert model for health technology procurement planning in
      hospitals.
AB  - Although in the last years technology innovation in healthcare brought big
      improvements in care level and patient quality of life, hospital complexity and
      management cost became higher. For this reason, necessity of planning for medical
      equipment procurement within hospitals is getting more and more important in
      order to sustainable provide appropriate technology for both routine activity and
      innovative procedures. In order to support hospital decision makers for
      technology procurement planning, an expert model was designed as reported in the
      following paper. It combines the most widely used approaches for technology
      evaluation by taking into consideration Health Technology Assessment (HTA) and
      Medical Equipment Replacement Model (MERM). The designing phases include a first
      definition of prioritization algorithms, then the weighting process through
      experts' interviews and a final step for the model validation that included both
      statistical testing and comparison with real decisions. In conclusion, the
      designed model was able to provide a semi-automated tool that through the use of
      multidisciplinary information is able to prioritize different requests of
      technology acquisition in hospitals. Validation outcomes improved the model
      accuracy and created different "user profiles" according to the specific needs of
      decision makers. 

PMID- 25570747
TI  - A pilot study of a plantar sensory evaluation system for early screening of
      diabetic neuropathy in a weight-bearing position.
AB  - The purpose of this study is to develop smart equipment to quantify plantar
      tactile sensibility for the early diagnosis and tracking of peripheral neuropathy
      caused by diabetes mellitus. In this paper, we offer a new testing system that is
      composed of a plantar tactile stimulation platform with a small moving contactor
      to stretch the skin tangentially, a response switch for each tactile stimulus, a
      motor control box, and a personal computer (PC) for psychophysical data
      processing. This quantitative sensory testing system has detailed measurements
      available and is easy to use compared with the conventional testing devices, such
      as von Frey monofilaments, pin-prick testing devices, and current perception
      threshold testers. When using our testing system in a weight-bearing position, we
      observed that the plantar tactile thresholds for the tangential stretching
      stimulus on the plantar surface of the foot ranged from approximately 10 um to 30
      um for healthy subjects. However, the threshold for a subject with diabetes was
      nearly three times higher than that for healthy subjects. The significant
      difference between these values suggests that the plantar sensory evaluation
      system using the lateral skin stretch stimulation can be used for early
      diagnosis, for the accurate staging of diabetic neuropathy, and for evaluating
      its progression noninvasively in a clinic and at home. 

PMID- 25570748
TI  - The effect of powered prosthesis control signals on trial-by-trial adaptation to
      visual perturbations.
AB  - Powered prostheses have the potential to restore abilities lost to amputation;
      however, many users report dissatisfaction with the control of their devices. The
      high variability of the EMG signals used to control powered devices likely
      burdens amputees with high movement uncertainty. In able-bodied subjects
      uncertainty affects adaptation, control, and feedback processing, which are often
      modeled using Bayesian statistics. Understanding the role of uncertainty for
      amputees might thus be important for the design and control of prosthetic
      devices. Here we quantified the role of uncertainty using a visual trial-by-trial
      adaptation approach. We compared adaptation behavior with two control interfaces
      meant to mimic able-bodied and prosthesis control: torque control and EMG
      control. In both control interfaces, adaptation rate decreased with high feedback
      uncertainty and increased with high mean error. However, we did observe different
      patterns of learning as the experiment progressed. For torque control, subjects
      improved and consequently adapted slower as the experiment progressed, while no
      such improvements were made for EMG control. Thus, EMG control resulted in
      overall adaptation behavior that supports Bayesian models, but with altered
      learning patterns and higher errors. These findings encourage further studies of
      adaptation with powered prostheses. A better understanding of the factors that
      alter learning patterns and errors will help design prosthesis control systems
      that optimize learning and performance for the prosthesis user. 

PMID- 25570749
TI  - Robot-assisted motor training: assistance decreases exploration during
      reinforcement learning.
AB  - Reinforcement learning (RL) is a form of motor learning that robotic therapy
      devices could potentially manipulate to promote neurorehabilitation. We developed
      a system that requires trainees to use RL to learn a predefined target movement.
      The system provides higher rewards for movements that are more similar to the
      target movement. We also developed a novel algorithm that rewards trainees of
      different abilities with comparable reward sizes. This algorithm measures a
      trainee's performance relative to their best performance, rather than relative to
      an absolute target performance, to determine reward. We hypothesized this
      algorithm would permit subjects who cannot normally achieve high reward levels to
      do so while still learning. In an experiment with 21 unimpaired human subjects,
      we found that all subjects quickly learned to make a first target movement with
      and without the reward equalization. However, artificially increasing reward
      decreased the subjects' tendency to engage in exploration and therefore slowed
      learning, particularly when we changed the target movement. An anti-slacking
      watchdog algorithm further slowed learning. These results suggest that robotic
      algorithms that assist trainees in achieving rewards or in preventing slacking
      might, over time, discourage the exploration needed for reinforcement learning. 

PMID- 25570750
TI  - Alteration in cardiovascular and postural control relationship in non-fainting
      elderly individuals.
AB  - It is known that standing induces orthostatic stress on the cardiovascular
      system. Our previous works have presented that the postural control during
      standing and cardiovascular changes are related to each other in the health young
      individuals. However, it remains to be checked if such a relationship is present
      in the elderly individuals as well. The present study conducted experiments
      similar to our previous studies and collected data for the muscle activation in
      lower leg muscles along with blood pressure during a passive stand test.
      Application of wavelet transform coherence method provided time frequency
      distribution of the coherence between the two signals. High coherence
      (>threshold) was observed between the two signals suggesting a strong
      relationship. Additionally, a frequency dependent behavior was observed between
      the two signals. The results from this study present strong evidence that there
      is a change in the relationship between the two signals with aging. 

PMID- 25570751
TI  - Enhancing practical multifunctional myoelectric applications through implicit
      motor control training systems.
AB  - Despite holding promise for advances in prostheses and robot teleoperation,
      myoelectric controlled interfaces have had limited impact in commercial
      applications. Simultaneous multifunctional controls are desired, but often lead
      to frustration by users who cannot easily control the devices using state-of-the
      art control schemes. This paper proposes and validates the use of implicit motor
      control training systems (IM-CTS) to achieve practical implementations of
      multifunctional myoelectric applications. Subjects implicitly develop muscle
      synergies needed to control a robotic application through an analogous visual
      interface without the associated physical constraints which may hinder learning.
      The learning then naturally transfers to perceived intuitive and robust control
      of the robotic device. The efficacy of the method is tested by comparing
      performance between two groups learning controls implicitly via the visual
      interface and explicitly via the robotic interface, respectively. The groups
      achieved comparable performance when performing tasks with the robotic device a
      week later. Moreover, the initial performance of the experimental group was
      significantly better than the control group achieved after up to 75 minutes of
      training. These findings support the use of IMCTS to achieve practical
      multifunctional control of a wide range of myoelectric applications without
      limiting them to intuitive mappings nor anthropomorphic devices. 

PMID- 25570752
TI  - Locomotor training through a 3D cable-driven robotic system for walking function
      in children with cerebral palsy: a pilot study.
AB  - Locomotor training using treadmill has been shown to elicit significant
      improvements in locomotor ability for some children with cerebral palsy (CP), the
      functional gains are relatively small and it requires greater involvement from a
      physical therapist. Current robotic gait training systems are effective in
      reducing the strenuous work of a physical therapist during locomotor training,
      but are less effective in improving locomotor function in some children with CP
      due to the limitations of the systems. Thus, a 3D cable-driven robotic gait
      training system was developed and tested in five children with CP through a 6
      week of long-term gait training. Results indicated that both overground walking
      speed and 6 minute walking distance improved after robot assisted treadmill
      training through the cable-driven robotic system, and partially retained at 8
      weeks after the end of training. Results from this pilot study indicated that it
      seems feasible to conduct locomotor training in children with CP through the 3D
      cable-driven robotic system. 

PMID- 25570753
TI  - Electrophysiological and behavioral measures of visuo-motor learning for
      application in movement disorders.
AB  - Dystonia is the third most common movement disorder worldwide and drastically
      reduces the quality of life of those who are affected. Despite its prevalence,
      very little is known about the underlying pathology of the disorder. Recent
      literature has suggested that abnormal processing in the superior colliculus (SC)
      may play a role in Dystonia. The SC is known to be an important hub in the neural
      network that is used when learning a novel movement and therefore we would
      postulate that a disorder of SC should result in abnormal movement learning. Here
      9 participants completed learning and non-learning movement tasks while
      behavioural and electrophysiological data were acquired. The results of this
      study show that there is a significant relationship between the behavioural and
      electrophysiological data (R(2) = 0.19, F(1, 46) =10.88, p < 0.002) during the
      learning task but not in the non-learning task (p > 0.05). The developed paradigm
      is ideally suited for probing the underlying pathology of Dystonia via movement
      learning.

PMID- 25570754
TI  - Estimation of continuous multi-DOF finger joint kinematics from surface EMG using
      a multi-output Gaussian Process.
AB  - Surface electromyographic (EMG) signals have often been used in estimating upper
      and lower limb dynamics and kinematics for the purpose of controlling robotic
      devices such as robot prosthesis and finger exoskeletons. However, in estimating
      multiple and a high number of degrees-of-freedom (DOF) kinematics from EMG,
      output DOFs are usually estimated independently. In this study, we estimate
      finger joint kinematics from EMG signals using a multi-output convolved Gaussian
      Process (Multi-output Full GP) that considers dependencies between outputs. We
      show that estimation of finger joints from muscle activation inputs can be
      improved by using a regression model that considers inherent coupling or
      correlation within the hand and finger joints. We also provide a comparison of
      estimation performance between different regression methods, such as Artificial
      Neural Networks (ANN) which is used by many of the related studies. We show that
      using a multi-output GP gives improved estimation compared to multi-output ANN
      and even dedicated or independent regression models. 

PMID- 25570755
TI  - Statistics of inter-spike intervals as a routine measure of accuracy in automatic
      decomposition of surface electromyogram.
AB  - Automated motor unit (MU) decomposition algorithms of surface electromyogram
      (EMG) have been developed recently. However, a routine estimate of the
      decomposition accuracy is still lacking. The objective of this preliminary study
      was to examine the statistics of the inter-spike intervals (ISIs) of the
      identified MUs as a measure of the decomposition accuracy, such that the ISI
      analysis can be used as a routine procedure to assess the accuracy of the surface
      identified MU spike timings. A surface EMG recording and decomposition system was
      used to record EMG signals and extract single MU activities from the first dorsal
      interosseous muscle of three healthy individuals. The estimated ISI statistics
      were cross-validated with decomposed MUs from simultaneous intramuscular EMG
      recordings. Our preliminary results reveal that the distribution of the ISIs,
      specifically the deviation from the Gaussian distribution as represented by
      secondary peaks at the short or long ISIs, can provide information regarding the
      spurious errors and missed firing errors in the decomposition. In addition, the
      variability (coefficient of variation) of the ISIs also correlated inversely with
      the decomposition accuracy. These findings show that the ISI statistics can be
      used to assess the spike timing accuracy of the identified MUs from surface EMG
      decomposition algorithms. 

PMID- 25570756
TI  - Classification of hand movements in amputated subjects by sEMG and
      accelerometers.
AB  - Numerous recent studies have aimed to improve myoelectric control of prostheses.
      However, the majority of these studies is characterized by two problems that
      could be easily fulfilled with recent resources supplied by the scientific
      literature. First, the majority of these studies use only intact subjects, with
      the unproved assumption that the results apply equally to amputees. Second,
      usually only electromyography data are used, despite other sensors (e.g.,
      accelerometers) being easy to include into a real life prosthesis control system.
      In this paper we analyze the mentioned problems by the classification of 40 hand
      movements in 5 amputated and 40 intact subjects, using both sEMG and
      accelerometry data and applying several different state of the art methods. The
      datasets come from the NinaPro database, which supplies publicly available sEMG
      data to develop and test machine learning algorithms for prosthetics. The number
      of subjects can seem small at first sight, but it is not considering the
      literature of the field (which has to face the difficulty of recruiting trans
      radial hand amputated subjects). Our results indicate that the maximum average
      classification accuracy for amputated subjects is 61.14%, which is just 15.86%
      less than intact subjects, and they show that intact subjects results can be used
      as proxy measure for amputated subjects. Finally, our comparison shows that
      accelerometry as a modality is less affected by amputation than electromyography,
      suggesting that real life prosthetics performance may easily be improved by
      inclusion of accelerometers. 

PMID- 25570757
TI  - Synergy analysis as a tool to design and assess an effective stroke
      rehabilitation.
AB  - The poor rehabilitation success rate, including the cases of ineffective and
      detrimental adaptations, make stroke a leading cause of disability. Thus, it is
      essential to recognize the mechanisms driving healthy motor recovery to improve
      such rate. Stroke alters the Synergy Architecture (SA), the modular muscle
      control system. So SA analysis may constitute a powerful tool to design and
      assess rehabilitation procedures. However, current impairment scales do not
      consider the patient's neuromuscular state. To gain insights into this
      hypothesis, we recorded multiple myoelectric signals from upper-limb muscles, in
      healthy subjects, while executing a set of common rehabilitation exercises. We
      found that SA reveals optimized motor control strategies and the positive effects
      of the use of visual feedback (VF) on motor control. Furthermore we demonstrate
      that the right and left arm's SA share the basic structure within the same
      subject, so we propose using the unaffected limb's SA as a reference motion
      pattern to be reached through rehabilitation. 

PMID- 25570758
TI  - Effects of very short pauses on electromyographic variables measured during
      fatiguing isometric contractions.
AB  - 15 healthy men (26.6 +/- 4.6 years old, weight of 70.7 +/- 8.6 kg, and height of
      1.750 +/- 0.072 m) performed three 30-seconds isometric contractions at 60% MVC,
      with two 10-seconds resting intervals between them. The goal was to study the
      effect of the resting intervals on the variables that are most commonly used to
      analyze surface electromyographic (S-EMG) signals (conduction velocity [CV], root
      mean square [RMS], average rectified value [ARV], mean power frequency [MNF], and
      median power frequency [MDF]). For the first 30-second contraction, the S-EMG
      variables behaved exactly like described in the literature. However, after the
      first and second pauses, the CV variable ceased to behave like in the literature.
      In the first contraction, the conduction velocity had a statistically significant
      decreasing trend, in the second contraction, it had a statistically non
      significant positive trend, and, in the third contraction, a statistically
      significant positive trend. These results suggest that short pauses between
      isometric constant-force contractions lead to changes in the recruiting
      strategies of the muscles involved in the contraction. The causes of these
      changes are not yet clear, and further work is needed in order to understand this
      effect. 

PMID- 25570759
TI  - Internal muscle activity imaging from multi-channel surface EMG recordings: a
      validation study.
AB  - The developed muscle activity imaging approach (MAI) was validated with surface
      EMG and intramuscular EMG signals simultaneously acquired from the biceps of a
      healthy male subject. 128 unipolar channels were employed for surface EMG
      measurement and one bipolar channel was employed for simultaneous intramuscular
      EMG measurement for the validation purpose. Ultrasound scans were also
      specifically performed to localize the location of the wire electrode inserted
      into the biceps. The surface EMG measurements, after noise filtering and signal
      decomposition, were used to reconstruct the internal muscle activities for the
      biceps by using the MAI approach. The locations of the reconstructed muscle
      activities were compared against the location of the wire electrode in the biceps
      identified from ultrasound images. Results demonstrate the feasibility and
      validity of the MAI approach in imaging internal muscle activities from multi
      channel surface EMG recordings. 

PMID- 25570760
TI  - Age-related differentiation of sensorimotor control strategies during pursuit and
      compensatory tracking.
AB  - Motor control deficits during aging have been well-documented. Various causes of
      neuromotor decline, including both peripheral and central neurological deficits,
      have been hypothesized. Here, we use a model of closed-loop sensorimotor control
      to examine the functional causes of motor control deficits during aging. We
      recruited 14 subjects aged 19-61 years old to participate in a study in which
      they performed single-joint compensatory and pursuit tracking tasks with their
      dominant hand. We found that visual response delay and visual noise increased
      with age, while reliance on visual feedback, especially during compensatory
      tracking decreased. Increases in visual noise were also positively correlated
      with increases in movement error during a reach and hold task. The results
      suggest an increase in noise within the visuomotor control system may contribute
      to the decline in motor performance during early aging. 

PMID- 25570761
TI  - Can transcranial direct current stimulation enhance performance of myoelectric
      control for multifunctional prosthesis?
AB  - Pattern recognition based myoelectric control has been studied by many
      researchers. However, the classification accuracy was pretty low for amputees
      towards multifunctional prosthesis control in practice. In this work, a novel
      method of transcranial direct current stimulation (tDCS) which can modulate brain
      activity was used to enhance performance for myoelectric prosthesis control. The
      pilot study was conducted on three able-bodied subjects and one transradial
      amputee. Surface electromyography (EMG) signals were acquired from both arms when
      performing eleven hand and wrist motions in pre-tDCS and post-tDCS sessions. Time
      domain (TD) features and linear discriminant analysis (LDA) classifier were
      adopted to process EMG. For the non-dominant hand of the healthy subjects, active
      anodal tDCS of the contralateral primary motor cortex was able to significantly
      improve average classification accuracy by 3.82% (p <; 0.05), while sham tDCS
      could not have such effect (p > 0.05). For amputated (phantom) hand of the
      amputee, active anodal tDCS was able to significantly improve average
      classification accuracy by 12.56%, while sham tDCS could not have such effect.
      For the dominant hand and intact hand, the average classification accuracies were
      stable and not significantly improved using either active tDCS or sham tDCS. The
      results show that tDCS is a powerful noninvasive method to modulate brain
      function and enhance EMG classification performance especially for the amputated
      hand towards multifunctional prosthesis control. The method proposed has a huge
      potential to promote EMG pattern recognition based control scheme to clinical
      application. 

PMID- 25570762
TI  - Changes of HD-sEMG maps of the upper limb during isometric endurance
      contractions.
AB  - Recent research in the field of surface EMG recorded with 2D electrode arrays
      have shown muscle adaptations as reflected on the spatial activation of motor
      units in response to pain, direction of movement or fatigue. The purpose of this
      study was to evaluate time- changes in the activation maps of upper limb muscles
      during endurance tasks associated with the degrees of freedom at the elbow joint.
      Preliminary results show time-variations in the distribution of intensity, that
      is, in the spatial recruitment of motor units, and that such changes may be
      dependent on the type of task. 

PMID- 25570763
TI  - Optimizing pattern recognition-based control for partial-hand prosthesis
      application.
AB  - Partial-hand amputees often retain good residual wrist motion, which is essential
      for functional activities involving use of the hand. Thus, a crucial design
      criterion for a myoelectric, partial-hand prosthesis control scheme is that it
      allows the user to retain residual wrist motion. Pattern recognition (PR) of
      electromyographic (EMG) signals is a well-studied method of controlling
      myoelectric prostheses. However, wrist motion degrades a PR system's ability to
      correctly predict hand-grasp patterns. We studied the effects of (1) window
      length and number of hand-grasps, (2) static and dynamic wrist motion, and (3)
      EMG muscle source on the ability of a PR-based control scheme to classify
      functional hand-grasp patterns. Our results show that training PR classifiers
      with both extrinsic and intrinsic muscle EMG yields a lower error rate than
      training with either group by itself (p<0.001); and that training in only
      variable wrist positions, with only dynamic wrist movements, or with both
      variable wrist positions and movements results in lower error rates than training
      in only the neutral wrist position (p<0.001). Finally, our results show that both
      an increase in window length and a decrease in the number of grasps available to
      the classifier significantly decrease classification error (p<0.001). These
      results remained consistent whether the classifier selected or maintained a hand
      grasp.

PMID- 25570764
TI  - Application of wavelet packet transform on myoelectric pattern recognition for
      upper limb rehabilitation after stroke.
AB  - Myoelectric pattern recognition applied to high-density surface electromyographic
      (sEMG) recordings from paretic muscles has been proven to identify various
      movement intents of stroke survivors, thus facilitating the design of
      myoelectrically controlled robotic systems for recovery of upper-limb dexterity.
      Aiming at effectively decoding neural control information under the condition of
      neurological injury following stroke, this paper further investigates the
      application of wavelet packet transform (WPT) on myoelectric feature extraction
      to identify 20 functional movements performed by the paretic upper limb of 4
      chronic stroke subjects. The WPT was used to decompose the original sEMG signals
      via a tree of subspaces, where optimal ones were selected in term of the
      classification efficacy. The energies in the selected subspaces were calculated
      as optimal wavelet packet features, which were finally fed into a linear
      discriminant classifier. The WPT-based myoelectric feature extraction approach
      achieved accuracies above 94% for all subjects in a user-specific condition,
      demonstrating its potential applications in upper limb rehabilitation after
      stroke. 

PMID- 25570765
TI  - Tongue motor training support system.
AB  - In this paper, we introduce a new tongue-training system that can be used for
      improvement of the tongue's range of motion and muscle strength after dysphagia.
      The training process is organized in game-like manner. Initially, we analyzed
      surface electromyography (EMG) signals of the suprahyoid muscles of five subjects
      during tongue-training motions. This test revealed that four types tongue
      training motions and a swallowing motion could be classified with 93.5% accuracy.
      Recognized EMG signals during tongue motions were designed to allow control of a
      mouse cursor via intentional tongue motions. Results demonstrated that simple PC
      games could be played by tongue motions, achieving in this way efficient,
      enjoyable and pleasant tongue training. Using the proposed method, dysphagia
      patients can choose games that suit their preferences and/or state of mind. It is
      expected that the proposed system will be an efficient tool for long-term tongue
      motor training and maintaining patients' motivation. 

PMID- 25570766
TI  - Joint force estimation using time-varying SEMG feature in fatiguing contraction.
AB  - Many studies have estimated joint force using surface electromyography (SEMG),
      however, the time-variant characteristic of SEMG is not considered. The change of
      SEMG amplitude is one of manifestations of muscle fatigue. This study proposes a
      force estimation method using SEMG in fatiguing contraction. The SEMG amplitude
      is used to determine the signal states by k-means clustering method. According to
      the signal state changes, the corresponding gain is used to estimate the force.
      The target contraction is an isometric abduction of an index finger in static and
      dynamic force conditions for 5 healthy subjects. The estimation performance was
      evaluated by percentage of root mean squared error (RMSE). The RMSE for the
      proposed method is 2.5 +/- 1.0% under static condition and 8.8 +/- 1.2% under
      dynamic condition. The accuracy using a constant gain calculated at initial time
      was used to compare with the proposed method. The RMSE are 8.9 +/- 2.2% under
      static condition and 10.1 +/- 2.4% under dynamic condition. The proposed method
      had better performance in both conditions.

PMID- 25570767
TI  - Muscle synergy analysis for similar upper limb motion tasks.
AB  - Muscle synergy is considered as a vector specifying a pattern of relative muscle
      activation. The goal of this paper is to explore whether there exists
      similarities between muscle synergies in similar upper limb motion tasks. One
      center-out-center reaching task and two path movement tasks with regard to the
      elbow and shoulder joints were designed, and seven healthy adults were recruited
      in this study. Surface electromyographic (sEMG) signals were recorded from 10
      upper arm and shoulder muscles, and muscle synergies were extracted using
      nonnegative matrix factorization algorithm. Although there existed individual
      differences among subjects, experimental results showed that the structures of
      muscle synergies extracted from these three similar tasks were similar on the
      ground of the values of Pearson's correlation coefficient was greater than 0.85.
      Through this finding, the neuromuscular control strategies of upper limb in
      similar tasks could be explained clearly, which also provided significant
      evidence to support the hypothesis of muscle synergies. 

PMID- 25570768
TI  - Haptic proprioception in a virtual locomotor task.
AB  - Normal gait needs both proprioceptive and visual feedback to the nervous system
      to effectively control the rhythmicity of motor movement. Current preprogrammed
      exoskeletons provide only visual feedback with no user control over the foot
      trajectory. We propose an intuitive controller where hand trajectories are mapped
      to control contralateral foot movement. Our study shows that proprioceptive
      feedback provided to the users hand in addition to visual feedback result in
      better control during virtual ambulation than visual feedback alone. Hand
      trajectories resembled normal foot trajectories when both proprioceptive and
      visual feedback was present. Our study concludes that haptic feedback is
      essential for both temporal and spatial aspects of motor control in rhythmic
      movements. 

PMID- 25570769
TI  - Using fuzzy logic in psychophysical experiments to separate hits, false positives
      and guesses in posturally perturbed standing subjects.
AB  - In a 2-Alternative Forced Choice Interval task (2AFCi), a standing subject is
      required to press a button once or twice to signal in which of two 4 s sequential
      intervals that (s)he thought that a short <= 16 mm postural perturbation had
      occurred. The perturbation might or might not result in transient changes of the
      subject's Anterior-Posterior Center of Pressure (APCOP) or in other measures.
      This paper used fuzzy inference to explore whether the correctness of a subject's
      stimulus detection can be gleaned from analyzing changes in one of more metrics
      related to changes in the APCOP. Also, distinguishing guesses from correct
      responses is a critical issue in any psychophysical detection paradigm.
      Biomechanical and psychophysical data are used to design a prediction model based
      on fuzzy inference that is able to discriminate correct responses from guesses.

PMID- 25570771
TI  - Brain-computer interface using P300 and virtual reality: a gaming approach for
      treating ADHD.
AB  - This paper presents a novel brain-computer interface (BCI) system aiming at the
      rehabilitation of attention-deficit/hyperactive disorder in children. It uses the
      P300 potential in a series of feedback games to improve the subjects' attention.
      We applied a support vector machine (SVM) using temporal and template-based
      features to detect these P300 responses. In an experimental setup using five
      subjects, an average error below 30% was achieved. To make it more challenging
      the BCI system has been embedded inside an immersive 3D virtual reality (VR)
      classroom with simulated distractions, which was created by combining a low-cost
      infrared camera and an "off-axis perspective projection" algorithm. This system
      is intended for kids by operating with four electrodes, as well as a non
      intrusive VR setting. With the promising results, and considering the simplicity
      of the scheme, we hope to encourage future studies to adapt the techniques
      presented in this study. 

PMID- 25570770
TI  - Usability testing of gaming and social media applications for stroke and cerebral
      palsy upper limb rehabilitation.
AB  - As part of the FEATHERS (Functional Engagement in Assisted Therapy Through
      Exercise Robotics) project, two motion tracking and one social networking
      applications were developed for upper limb rehabilitation of stroke survivors and
      teenagers with cerebral palsy. The project aims to improve the engagement of
      clients during therapy by using video games and a social media platform. The
      applications allow users to control a cursor on a personal computer through
      bimanual motions, and to interact with their peers and therapists through the
      social media. The tracking applications use either a Microsoft Kinect or a
      PlayStation Eye camera, and the social media application was developed on
      Facebook. This paper presents a usability testing of these applications that was
      conducted with therapists from two rehabilitation clinics. The "Cognitive
      Walkthrough" and "Think Aloud" methods were used. The objectives of the study
      were to investigate the ease of use and potential issues or improvements of the
      applications, as well as the factors that facilitate and impede the adoption of
      technology in current rehabilitation programs. 

PMID- 25570772
TI  - Correlation of reaching and grasping kinematics and clinical measures of upper
      extremity function in persons with stroke related hemiplegia.
AB  - Timed measures of standardized functional tasks are commonly used to measure
      treatment effects in persons with upper extremity (UE) paresis due to stroke. The
      effectiveness of their ability to measure motor recovery has come into question
      because of their inability to distinguish between motor recovery and
      compensations. This paper presents three linear regression models generated from
      twelve kinematic measures collected during the performance of a two phase
      reach/grasp and transport /release activity as performed by 21 persons with upper
      extremity hemiparesis due to chronic stroke. One of these models demonstrated a
      statistically significant correlation with the subjects' scores on the Wolf Motor
      Function Test (WMFT), a battery of fifteen standardized upper extremity
      functional activities. The second and third models demonstrated a statistically
      significant correlation with the subjects' WMFT change scores elicited by a two
      week intensive upper extremity motor rehabilitation intervention. The high
      correlation suggests that models of kinematic measurements can be used to predict
      neurologic improvement and the effectiveness of treatment. 

PMID- 25570773
TI  - A novel upper limb rehabilitation system with self-driven virtual arm illusion.
AB  - This paper proposes a novel upper extremity rehabilitation system with virtual
      arm illusion. It aims for fast recovery from lost functions of the upper limb as
      a result of stroke to provide a novel rehabilitation system for paralyzed
      patients. The system is integrated with a number of technologies that include
      Augmented Reality (AR) technology to develop game like exercise, computer vision
      technology to create the illusion scene, 3D modeling and model simulation, and
      signal processing to detect user intention via EMG signal. The effectiveness of
      the developed system has evaluated via usability study and questionnaires which
      is represented by graphical and analytical methods. The evaluation provides with
      positive results and this indicates the developed system has potential as an
      effective rehabilitation system for upper limb impairment. 

PMID- 25570774
TI  - Feedback control of biomimetic exotendon device for hand rehabilitation in
      stroke.
AB  - Many hand exoskeleton devices have recently been developed for hand
      rehabilitation of stroke survivors, but most hand exoskeletons focused on
      implementing joint movement driven by individual actuator located at the finger
      joints rather than considering function of hand muscle-tendons and their
      coordination. In order to achieve hand rehabilitation targeted on restoration of
      specific muscle-tendon functions, a biomimetic hand exotendon device (BiomHED)
      was introduced recently. This paper introduces a ring-type design of exotendon
      device for easier donning and the design of a feedback control system for
      controlling posture of the finger. Technical details of the feedback sensor and
      controller with preliminary experimental results are presented. 

PMID- 25570775
TI  - A novel BCI-controlled pneumatic glove system for home-based neurorehabilitation.
AB  - Commercially available devices for Brain-Computer Interface (BCI)-controlled
      robotic stroke rehabilitation are prohibitively expensive for many researchers
      who are interested in the topic and physicians who would utilize such a device.
      Additionally, they are cumbersome and require a technician to operate, increasing
      the inaccessibility of such devices for home-based robotic stroke rehabilitation
      therapy. Presented here is the design, implementation and test of an inexpensive,
      portable and adaptable BCI-controlled hand therapy device. The system utilizes a
      soft, flexible, pneumatic glove which can be used to deflect the subject's wrist
      and fingers. Operation is provided by a custom-designed pneumatic circuit. Air
      flow is controlled by an embedded system, which receives serial port instruction
      from a PC running real-time BCI software. System tests demonstrate that glove
      control can be successfully driven by a real-time BCI. A system such as the one
      described here may be used to explore closed loop neurofeedback rehabilitation in
      stroke relatively inexpensively and potentially in home environments. 

PMID- 25570776
TI  - Classification of gait quality for biofeedback to improve heel-to-toe gait.
AB  - A feature of healthy gait is a clearly defined heel strike upon initial contact
      of the foot with the ground. However, a common consequence of ageing is
      deterioration of the heel first nature of gait towards a shuffling gait (flat
      foot at contact). Physiotherapy can be effective in correcting this but is costly
      and labour intensive. Gait rehabilitation could be accelerated with home
      exercise, guided by a biofeedback device that distinguishes between heel first
      and shuffling gait. This paper describes an algorithm that distinguishes between
      heel-to-toe gait and shuffling gait on the basis of angular velocity of the foot,
      using an inertial measurement unit. Measurements were made of normal and abnormal
      gait and used to develop an algorithm that distinguishes between good and bad
      steps. Results demonstrate very good algorithm performance, with a classification
      accuracy at the accuracy-optimal threshold of 92.7% when compared with
      physiotherapist labels. The sensitivity and specificity at this threshold are
      84.4% and 97.5% respectively. These performance metrics suggest that this
      algorithm is usable in a biofeedback device. 

PMID- 25570777
TI  - Assessment of neurofeedback training by means of motor imagery based-BCI for
      cognitive rehabilitation.
AB  - The age-related impairment is an increasing problem due to the aging suffered by
      the population, especially in developed countries. It is usual to use
      electroencephalogram (EEG)-based Brain Computer Interface (BCI) systems by means
      of the signal in order to assist and to improve the quality of life of people
      with disabilities. However, a parallel research line addresses the problem by the
      use of BCI systems as a way to train cognitive areas to achieve a deceleration of
      cognitive impairment or even an improvement. In this regard, a neurofeedback
      training (NFT) tool using motor imagery-based BCI, was developed. Training
      consists on imagery motor exercises combined with memory and logical relation
      tasks. In order to assess the effectiveness of the application 40 subjects, older
      than 59 years old, took part in this study. Our NFT application was tested by 20
      subjects and their scores of a neuropsychological test were compared with the
      remaining 20 subjects who did not perform the NFT. Results show a significant
      improvement of three cognitive features after performing the NFT: visual
      perception, expressive speech, and immediate memory. Therefore, evidences show
      that the performance of a NFT tool based on motor imagery tasks could be a
      positive activity for slow down the aging effects. 

PMID- 25570778
TI  - Toward an affordable and user-friendly visual motion capture system.
AB  - The present study aims at designing and evaluating a low-cost, simple and
      portable system for arm joint angle estimation during grasping-like motions. The
      system is based on a single RGB-D camera and three customized markers. The
      automatically detected and tracked marker positions were used as inputs to an
      offline inverse kinematic process based on bio-mechanical constraints to reduce
      noise effect and handle marker occlusion. The method was validated on 4 subjects
      with different motions. The joint angles were estimated both with the proposed
      low-cost system and, a stereophotogrammetric system. Comparative analysis shows
      good accuracy with high correlation coefficient (r= 0.92) and low average RMS
      error (3.8 deg). 

PMID- 25570779
TI  - A technological approach to studying motor planning ability in children at high
      risk for ASD.
AB  - In this work we propose a new method to study the development of motor planning
      abilities in children and, in particular, in children at high risk for ASD.
      Although several modified motor signs have been found in children with ASD, no
      specific markers enabling the early assessment of risk have been found yet. In
      this work, we discuss the problem posed by objective and quantitative behavioral
      analysis in non-structured environment. After an initial description of the main
      constraints imposed by the ecological approach, a technological and
      methodological solution to these issues is presented. Preliminary results on 12
      children are reported and briefly discussed. 

PMID- 25570780
TI  - A smartphone mediated portable intelligent medicine case for medication
      management support.
AB  - We developed an epoch-making portable intelligent medicine case for recipients
      who take medicine every day. The medicine case consists of a recipient's
      smartphone and a mirror-embedded pill organizer. The smartphone captures
      medicines in the storage compartments of the organizer by using its built-in
      camera. The positions and shapes of mirrors were optimized in order that the
      smartphone can confirm the whole spaces. The medicine case calculates changes
      caused by medications and approximates them by quadratic curves. If a fitted
      curve in a space was convex downward, the medicine case judged that there are
      medicines in the space. 

PMID- 25570781
TI  - Sharing Vital Signs between mobile phone applications.
AB  - We propose a communication library, ShareVitalSigns, for the standardized
      exchange of vital sign information between health applications running on mobile
      platforms. The library allows an application to request one or multiple vital
      signs from independent measurement applications on the Android OS. Compatible
      measurement applications are automatically detected and can be launched from
      within the requesting application, simplifying the work flow for the user and
      reducing typing errors. Data is shared between applications using intents, a
      passive data structure available on Android OS. The library is accompanied by a
      test application which serves as a demonstrator. The secure exchange of vital
      sign information using a standardized library like ShareVitalSigns will
      facilitate the integration of measurement applications into diagnostic and other
      high level health monitoring applications and reduce errors due to manual entry
      of information.

PMID- 25570782
TI  - The potential of m-health systems for diabetes management in post conflict
      regions a case study from Iraq.
AB  - The recent developments of m-health technologies particularly in the developing
      world are increasing sharply due to the importance and accelerated adoption of
      these technologies in the developing countries. However, there are few if any
      studies on the effectiveness of mobile health in post conflict regions especially
      in the Middle East region. In this paper we describe the design, implementation
      and clinical outcomes of a feasibility study on mobile diabetes management in
      Basra, Southern Iraq as an exemplar for the effectiveness of mobile health
      technologies for improved healthcare delivery in similar post conflict regions.
      The key clinical outcome of this study indicated the lowering of HbA1C levels in
      the mobile health group indicating the potential of deploying such technologies
      in these regions where health resources are limited and challenging. 

PMID- 25570783
TI  - Implementation of a smartphone as a wireless gyroscope application for the
      quantification of reflex response.
AB  - The patellar tendon reflex constitutes a fundamental aspect of the conventional
      neurological evaluation. Dysfunctional characteristics of the reflex response can
      augment the diagnostic acuity of a clinician for subsequent referral to more
      advanced medical resources. The capacity to quantify the reflex response while
      alleviating the growing strain on specialized medical resources is a topic of
      interest. The quantification of the tendon reflex response has been successfully
      demonstrated with considerable accuracy and consistency through using a potential
      energy impact pendulum attached to a reflex hammer for evoking the tendon reflex
      with a smartphone, such as an iPhone, application representing a wireless
      accelerometer platform to quantify reflex response. Another sensor integrated
      into the smartphone, such as an iPhone, is the gyroscope, which measures rate of
      angular rotation. A smartphone application enables wireless transmission through
      Internet connectivity of the gyroscope signal recording of the reflex response as
      an email attachment. The smartphone wireless gyroscope application demonstrates
      considerable accuracy and consistency for the quantification of the tendon reflex
      response. 

PMID- 25570784
TI  - Seamless personal health information system in cloud computing.
AB  - Noncontact ECG measurement has gained popularity these days due to its
      noninvasive and conveniences to be applied on daily life. This approach does not
      require any direct contact between patient's skin and sensor for physiological
      signal measurement. The noncontact ECG measurement is integrated with mobile
      healthcare system for health status monitoring. Mobile phone acts as the personal
      health information system displaying health status and body mass index (BMI)
      tracking. Besides that, it plays an important role being the medical guidance
      providing medical knowledge database including symptom checker and health fitness
      guidance. At the same time, the system also features some unique medical
      functions that cater to the living demand of the patients or users, including
      regular medication reminders, alert alarm, medical guidance, appointment
      scheduling. Lastly, we demonstrate mobile healthcare system with web application
      for extended uses, thus health data are clouded into web server system and web
      database storage. This allows remote health status monitoring easily and so forth
      it promotes a cost effective personal healthcare system. 

PMID- 25570785
TI  - PERCEPT-II: smartphone based indoor navigation system for the blind.
AB  - In this paper we introduce PERCEPT-II, a low cost and user friendly indoor
      navigation system for blind and visually impaired users. Using an Android
      Smartphone that runs PERCEPT-II application with accessibility features, the
      blind user obtains navigation instructions to the chosen destination when
      touching specific landmarks tagged with Near Field Communication tags. The system
      was deployed and tested in a large building at the University of Massachusetts at
      Amherst. 

PMID- 25570786
TI  - SUPAR: Smartphone as a ubiquitous physical activity recognizer for u-healthcare
      services.
AB  - Current generation smartphone can be seen as one of the most ubiquitous device
      for physical activity recognition. In this paper we proposed a physical activity
      recognizer to provide u-healthcare services in a cost effective manner by
      utilizing cloud computing infrastructure. Our model is comprised on embedded
      triaxial accelerometer of the smartphone to sense the body movements and a cloud
      server to store and process the sensory data for numerous kind of services. We
      compute the time and frequency domain features over the raw signals and evaluate
      different machine learning algorithms to identify an accurate activity
      recognition model for four kinds of physical activities (i.e., walking, running,
      cycling and hopping). During our experiments we found Support Vector Machine
      (SVM) algorithm outperforms for the aforementioned physical activities as
      compared to its counterparts. Furthermore, we also explain how smartphone
      application and cloud server communicate with each other. 

PMID- 25570787
TI  - Evaluation of wearable consumer heart rate monitors based on photopletysmography.
AB  - Wearable monitoring of heart rate (HR) during physical activity and exercising
      allows real time control of exercise intensity and training effect. Recently,
      technologies based on pulse plethysmography (PPG) have become available for
      personal health management for consumers. However, the accuracy of these monitors
      is poorly known which limits their application. In this study, we evaluated
      accuracy of two PPG based (wrist i.e. Mio Alpha vs forearm i.e. Schosche Rhythm)
      commercially available HR monitors during exercise. 21 healthy volunteers (15
      male and 6 female) completed an exercise protocol which included sitting, lying,
      walking, running, cycling, and some daily activities involving hand movements. HR
      estimation was compared against values from the reference electrocardiogram (ECG)
      signal. The heart rate estimation reliability scores for <;5% accuracy against
      reference were following: mio Alpha 77,83% and Scosche Rhytm 76,29%. The
      estimated results indicate that performance of devices depends on various
      parameters, including specified activity, sensor type and device placement. 

PMID- 25570788
TI  - Implementation of a smartphone for evaluating gait characteristics of a trans
      tibial prosthesis.
AB  - Smartphone applications have been demonstrated for their capacity to measure gait
      in functionally autonomous environments beyond the limitations of a traditional
      gait laboratory. A software application enables the iPhone to function as a
      wireless accelerometer platform. The recorded acceleration of gait can be
      transmitted wirelessly as an email attachment through Internet connectivity. The
      objective of the research was to demonstrate the capacity of the smartphone to
      quantify gait features of a trans-tibial prosthesis. The iPhone a standard
      smartphone was mounted to the carbon fiber blade of the prosthesis through an
      adapter developed by a 3D printer. The application demonstrated considerable
      accuracy and reliability for the quantification of gait characteristics. 

PMID- 25570789
TI  - Targeted and anonymized smartphone-based public health interventions in a
      participatory sensing system.
AB  - Public health interventions comprising information dissemination to affect
      behavioral adjustment have long been a significant component of public health
      campaigns. However, there has been limited development of public health
      intervention systems to make use of advances in mobile computing and
      telecommunications technologies. Such developments pose significant challenges to
      privacy and security where potentially sensitive data may be collected. In our
      previous work we identified and demonstrated the feasibility of using mobile
      devices as anonymous public health data collection devices as part of a Health
      Participatory Sensing Network (HPSN). An advanced capability of these networks
      extended in this paper would be the ability to distribute, apply, report on and
      analyze the usage and effectiveness of targeted public health interventions in an
      anonymous way. In this paper we describe such a platform, its place in the HPSN
      and demonstrate its feasibility through an implementation. 

PMID- 25570790
TI  - iBEST: intelligent Balance assessment and Stability Training system using
      smartphone.
AB  - Patients with postural instability could lead to falls and injuries while walking
      due to balance disorders. So those patients need regular balance training and
      evaluation to improve and examine balance deficiencies. But many do not notice
      such balance issues; resulting lack of timely preventive measures. This shows the
      needs of affordable and accessible solution for balance training and assessment.
      So iBEST (intelligent Balance assessment and Stability Training) is proposed
      enabling to train and assess balance conveniently anywhere anytime. Moreover,
      therapists can remotely evaluate and manage their recovery progress. These
      benefits can be realized leveraging sensors from smartphone, cloud-based data
      analytics and web applications. iBEST employs sensorised automated balance
      assessment in digitizing Berg Balance Scale (BBS) clinical risk assessment tool.
      The initial feasibility study showed average accuracy of 90.22% using smartphone
      in classifying the specified BBS test items. 

PMID- 25570791
TI  - Preliminary study for the personal handheld device based snoring detection in
      ordinary sleep situation.
AB  - Snoring is one of the representative phenomena of the sleep disorder and
      detection of snoring is quite important for improving quality of daily human
      life. The purpose of this research is to define the noises of the ordinary sleep
      situation and to find its characteristics as a preliminary research of snoring
      detection. Differently from previous snoring researches, we use a built-in sound
      recording system of Smartphone for practical use in ordinary sleep condition, and
      recording was carried out in a general private bedroom. Especially, we designed
      the experimental protocol, including the various noises could be frequently
      occurred during sleep such as cough, music, talking, alarm, door open/close, fan,
      radio and footstep to make closer to the actual sleep circumstance. The sound
      data set was recorded during actual sleep from 10 normal subjects. Totally 44
      snoring data set and 75-noise dataset is acquired and analyzed. 

PMID- 25570792
TI  - A single vs. multi-sensor approach to enhanced detection of smartphone placement.
AB  - In this paper, the authors evaluate the ability to detect on-body device
      placement of smartphones. A feasibility study is undertaken with N=5 participants
      to identify nine key locations, including in the hand, thigh and backpack, using
      a multitude of commonly available smartphone sensors. Sensors examined include
      the accelerometer, magnetometer, gyroscope, pressure and light sensors. Each
      sensor is examined independently, to identify the potential contributions it can
      offer, before a fused approach, using all sensors is adopted. A total of 139
      features are generated from these sensors, and used to train five machine
      learning algorithms, i.e. C4.5, CART, Naive Bayes, Multilayer Perceptrons, and
      Support Vector Machines. Ten-fold cross validation is used to validate these
      models, achieving classification results as high as 99%. 

PMID- 25570793
TI  - Non-invasive blood glucose monitor based on spectroscopy using a smartphone.
AB  - Development of a novel method for non-invasive measurement of blood glucose
      concentration using smartphone is discussed. Our research work has three major
      contributions to society and science. First, we modified and extended the Beer
      Lambert's law in physics to accommodate for multiple wavelengths. This extension
      can aid researchers who wish to perform optical spectroscopy. Second, we
      successfully developed a creative and non-invasive way for diabetic patients to
      measure glucose levels via a smartphone. Researchers and chemists can now use
      their smartphones to determine the absorbance and, therefore, concentration of a
      chemical. Third, we created an inexpensive way to perform optical spectroscopy by
      using a smartphone. Monitoring blood glucose using a smartphone application that
      simply uses equipment already available on smartphones will improve the lives of
      diabetic patients who can continuously check their blood glucose levels while
      avoiding the current inconvenient, unhygienic, and costly invasive glucose
      meters. 

PMID- 25570794
TI  - Interactive telemedicine solution based on a secure mHealth application.
AB  - In dynamic healthcare environments, caregivers and patients are constantly
      moving. To increase the healthcare quality when it is necessary, caregivers need
      the ability to reach each other and securely access medical information and
      services from wherever they happened to be. This paper presents an Interactive
      Telemedicine Solution (ITS) to facilitate and automate the communication within a
      healthcare facility via Voice over Internet Protocol (VOIP), regular mobile
      phones, and Wi-Fi connectivity. Our system has the capability to exchange/provide
      securely healthcare information/services across geographic barriers through 3G/4G
      wireless communication network. Our system assumes the availability of an
      Electronic Health Record (EHR) system locally in the healthcare organization
      and/or on the cloud network such as a nation-wide EHR system. This paper
      demonstrate the potential of our system to provide effectively and securely
      remote healthcare solution. 

PMID- 25570795
TI  - Distributed feedback laser for biosensing applications.
AB  - We present an organic semiconductor distributed feedback laser biosensor and
      demonstrate its sensing capabilities. Optimization of the gain layer thickness to
      maximize the response to refractive index changes and bulk sensing results are
      shown. Desthiobiotin-avidin sensing assay results are also presented and the
      potential to perform multiple, repeated sensing measurements is demonstrated. 

PMID- 25570796
TI  - Design of a single-fiber, wavelength-resolved system for monitoring deep tissue
      oxygenation.
AB  - We propose a single-fiber, zero source-detector separation system with wavelength
      resolved detection for measuring oxygen saturation in deep brain structures. The
      system consists of a white light emitting diode (LED) source, optics to couple
      light into a 240-MUm-diameter fiber, a beam splitter to separate the collected
      from the delivered photons and a spectrometer for detection. Depth resolution is
      achieved by inserting the fiber, comparable in size to microelectrodes used for
      electrophysiology, into the tissue of interest. Since most of the diffuse
      reflected light travels through a small volume at the tip of the fiber, this
      arrangement allows efficient collection of signal. Fresnel reflections are
      minimized using polarizers. Monte Carlo simulations across 400-1000 nm indicate
      that ~0.5% of the incident light can be collected and effectively interrogate a
      ~0.02 mm(3) volume at the fiber tip. System design, characterization data and
      phantom experiments using an absorptive dye in scattering media are presented.
      The simple nature of the instrumentation can potentially lead to a miniaturized
      system capable of detecting oxygen saturation in deep brain structures in freely
      moving animals. 

PMID- 25570797
TI  - A continuum body force sensor designed for flexible surgical robotics devices.
AB  - This paper presents a novel three-axis force sensor based on optical photo
      interrupters and integrated with the robot arm STIFF-FLOP (STIFFness controllable
      Flexible and Learnable Manipulator for Surgical Operations) to measure external
      interacting forces and torques. The ring-shape bio-compatible sensor presented
      here embeds the distributed actuation and sensing system of the STIFF-FLOP
      manipulator and is applicable to the geometry of its structure as well to the
      structure of any other similar soft robotic manipulator. Design and calibration
      procedures of the device are introduced: experimental results allow defining a
      stiffness sensor matrix for real-time estimation of force and torque components
      and confirm the usefulness of the proposed optical sensing approach. 

PMID- 25570798
TI  - Miniaturization of photoacoustic cell for smart endoscope to improve sensitivity.
AB  - Ultrathin endoscopes, such as transnasal endo-scopes, have been developed to
      alleviate discomfort during diagnosis and therapy. However, their application to
      optional diagnostics is limited since many optional diagnostic instruments are
      designed to fit through larger side channels. The aim of this study was to
      develop a smart endoscope that can obtain various diagnoses based on
      photoacoustic spectroscopy. The photoacoustic process comprises complex energy
      conversions involving optical, thermal, and elastic processes. This work focused
      on the scaling potential of photoacoustic sensors. Photoacoustic sensors with two
      different volumes were developed, and the amplitudes and frequency responses of
      the photoacoustic signals for silicone rubbers with six different Young's moduli
      were investigated. The results showed that photoacoustic signals can be enhanced
      by reducing the volumes of the sensors. Embedding a miniaturized photoacoustic
      sensor in an endoscope was confirmed to improve the sensitivity. 

PMID- 25570799
TI  - A portable multi-channel wireless NIRS device for muscle activity real-time
      monitoring.
AB  - Near-infrared spectroscopy (NIRS) is a relative new technology in monitoring
      muscle oxygenation and hemo-dynamics. This paper presents a portable multi
      channel wireless NIRS device for real-time monitoring of muscle activity. The
      NIRS sensor is designed miniaturized and modularized, to make multi-site
      monitoring convenient. Wireless communication is applied to data transmission
      avoiding of cumbersome wires and the whole system is highly integrated. Special
      care is taken to eliminate motion artifact when designing the NIRS sensor and
      attaching it to human skin. Besides, the system is designed with high sampling
      rate so as to monitor rapid oxygenation changes during muscle activities. Dark
      noise and long-term drift tests have been carried out, and the result indicates
      the device has a good performance of accuracy and stability. In vivo experiments
      including arterial occlusion and isometric voluntary forearm muscle contraction
      were performed, demonstrating the system has the ability to monitor muscle
      oxygenation parameters effectively even in exercise. 

PMID- 25570800
TI  - Effectiveness of the DreamSkin(r) garment on relieving symptoms of
      eczema/dermatitis using electrical and spectroscopic methods: A case study.
AB  - Eczema is a common skin inflammatory disorder particularly among children. The
      treatment of which usually consists of the application of emollients and
      moisturisers to maintain skin moisture and to reduce the risk of inflammation,
      infection and exacerbative factors. Recently, DreamSkin(r) Health Limited has
      developed a unique polymer treatment for eczema. The polymer has been applied to
      medical grade silk clothing as a means of delivering the therapeutic benefits to
      the sufferers' skin. They claim that the polymer reduces the loss of moisture
      caused by evaporation from damaged skin; acts as a barrier against external
      irritants and helps to restore the skin's natural temperature management process.
      The aim of this study was to assess the products effectiveness at providing
      symptomatic relief for a volunteer with confirmed eczema and atopic dermatitis
      over a period of 14 days. Both skin capacitance and NIR spectra were collected
      during the course of the study, using the Corneometer(r) CM 825 and a
      spectrophotometer equipped with a customized reflectance probe for measurements
      in the Near Infrared region. The treated area showed visibly improved skin and
      overall results from both techniques showed a noticeable increase in skin water
      content after 14 days, peaking on the 7th day. However, slight differences were
      observed in the 7 magnitude of increase between the two instruments. Future work
      will focus on expanding this study to include more cases as well as performing
      statistical analysis to build upon our previous work in the area of skin
      hydration determinations using Near Infrared Spectroscopy.

PMID- 25570801
TI  - Tracking gaze while walking on a treadmill: spatial accuracy and limits of use of
      a stationary remote eye-tracker.
AB  - Inaccurate visual sampling and foot placement may lead to unsafe walking. Virtual
      environments, challenging obstacle negotiation, may be used to investigate the
      relationship between the point of gaze and stepping accuracy. A measurement of
      the point of gaze during walking can be obtained using a remote eye-tracker. The
      assessment of its performance and limits of applicability is essential to define
      the areas of interest in a virtual environment and to collect information for the
      analysis of the visual strategy. The current study aims at characterizing a gaze
      eye-tracker in static and dynamic conditions. Three different conditions were
      analyzed: a) looking at a single stimulus during selected head movements b)
      looking at multiple stimuli distributed on the screen from different distances,
      c) looking at multiple stimuli distributed on the screen while walking. The eye
      tracker was able to measure the point of gaze during the head motion along medio
      lateral and vertical directions consistently with the device specifications,
      while the tracking during the head motion along the anterior-posterior direction
      resulted to be lower than the device specifications. During head rotation around
      the vertical direction, the error of the point of gaze was lower than 23 mm. The
      best accuracy (10 mm) was achieved, consistently to the device specifications, in
      the static condition performed at 650 mm from the eye-tracker, while point of
      gaze data were lost while getting closer to the eye-tracker. In general, the
      accuracy and precision of the point of gaze did not show to be related to the
      stimulus position. During fast walking (1.1 m/s), the eye-tracker did not lose
      any data, since the head range of motion was always within the ranges of
      trackability. The values of accuracy and precision during walking were similar to
      those resulting from static conditions. These values will be considered in the
      definition of the size and shape of the areas of interest in the virtual
      environment. 

PMID- 25570802
TI  - A self-powered 2-dimensional motion detection chip.
AB  - We demonstrate a self-powered chip to detect motion which enables constant, non
      invasive monitoring. The chip was implemented in a standard 0.18 MUm CMOS
      process. A P-N junction photodiode array was fabricated in the chip to detect
      when light is blocked by the movement of a hand or finger. The interface circuit
      detects the change between the shadowing and the exposure to determine the
      specific movement. This entire chip operates without any off-chip power supply
      and provides digitized outputs including 1 bit direction output and an 8 bits
      output indicative of the velocity in two dimensions. 

PMID- 25570803
TI  - Investigating skin barrier function utilizing reflectance NIR spectroscopy.
AB  - Near Infrared Spectroscopy is seen as a potentially valuable technique for skin
      analysis, and has been employed by many previous studies to measure skin
      hydration, since it is competent of providing information regarding various
      functional groups including OH, CH and NH bands. The aim of this study was to
      investigate the capability of further utilizing this method by attempting to
      analyze skin barrier function as well as water content, through the evaluation of
      skin water uptake on two test sites, one untreated, and another treated with a
      high lipid moisturizer for a period of 7 days. Reflectance NIRS measurements were
      supported by capacitance readings obtained using the Corneometer(r) CM 825.
      Baseline recordings taken on the first day following treatment showed that more
      differences were observed between the treated and untreated sites in the regions
      belonging to, or are influenced by CH and NH groups rather than purely on the
      water bands. On the hand, moisture levels measured after placing a wet patch on
      the skin remained nearly equal for both sites but second derivative spectra
      showed that a clear contrast existed between absorbance heights at the water
      bands of the treated and untreated, suggesting that moisturizer use could have
      limited water uptake to a more superficial layer of the skin, whereas for the
      untreated site, the opposite would have been true and water was able to penetrate
      deeper. Overall, results here suggest that NIR spectroscopy can possibly provide
      valuable information not only on skin water contents but perhaps on other skin
      parameters such as barrier function. 

PMID- 25570804
TI  - A pilot spectroscopy study on time-varying bioimpedance during electrically
      induced muscle contraction.
AB  - Alterations in the health of muscles can be evaluated through the use of
      electrical impedance myography (EIM). To date, however, nearly all work has
      relied upon single-frequency/spectroscopy stepped-sine measurements of static
      muscle (contracted or relaxed). In this work, we assessed the temporal
      alterations in the impedance spectrum (1 kHz to 1 MHz) behavior of gastrocnemius
      during the active process of muscle contraction. The approach is based on the
      multisine impedance spectroscopy technique. The gastrocnemii of a wild type mouse
      was measured during electrically-induced muscle contraction via direct current
      stimulation of the sciatic nerve. The processes of contraction and relaxation
      were clearly identified in the time-frequency impedance spectrum likely
      corresponding to an increase muscle fiber diameter. The technique of dynamic
      multisine EIM has the potential of providing useful insights into contractile
      mechanisms of muscle in health and disease. 

PMID- 25570805
TI  - Localized BIA identifies structural and pathophysiological changes in soft tissue
      after post-traumatic injuries in soccer players.
AB  - Localized bioimpedance (BIA) was measured with a single frequency phase-sensitive
      analyzer at 50 kHz in three post-traumatic types of injuries on four professional
      soccer players: (1) myositis ossificans, (2) intramuscular seroma and (3)
      trochanteric (hip) bursitis. Normal reference value (no injury) was obtained from
      the contra lateral not injured limb at a mirror-like location of the injury. The
      relative variations resistance (R) and reactance (Xc) at the time of injury was
      confronted with the not injured values. Relative variations between acute
      measurements and post medication ones on intramuscular seroma and bursitis have
      been computed. In intramuscular seroma and trochanteric bursitis we have obtained
      a percent of change between injury data and after medical intervention. On
      myositis ossificans, localized BIA showed a 7-8 % decrease in Xc whereas the
      percent of change of R was negligible (1 %). These percent of changes are in
      concordance with histological evidence. In the case of a presence of seroma or
      the lower thigh and trochanteric bursitis, the soft tissue cavity accumulates
      fluid. Post-injury localized BIA, relative with respect to non-injured side,
      confirmed sizeable soft tissue destruction evidenced by 50 % decrease of Xc and
      24-31 % decrease of R due to interstitial fluid accumulation. Once the seroma and
      the blood in the bursitis was removed the localized the immediate post-injury BIA
      parameters increased as follows: a) intramuscular seroma + 10 % on R and + 74 %
      of Xc; b) trochanteric bursitis + 20 % of R and +24 % of Xc. Localized BIA other
      than classifying soft tissue injuries, can be useful to understand the
      pathophysiology and structural impairments of other kind of injuries and to
      understand their behavior. 

PMID- 25570806
TI  - Measurement of signal use and vehicle turns as indication of driver cognition.
AB  - This paper uses data analytics to provide a method for the measurement of a key
      driving task, turn signal usage as a measure of an automatic over-learned
      cognitive function drivers. The paper augments previously reported more complex
      executive function cognition measures by proposing an algorithm that analyzes
      dashboard video to detect turn indicator use with 100% accuracy without any false
      positives. The paper proposes two algorithms that determine the actual turns made
      on a trip. The first through analysis of GPS location traces for the vehicle,
      locating 73% of the turns made with a very low false positive rate of 3%. A
      second algorithm uses GIS tools to retroactively create turn by turn directions.
      Fusion of GIS and GPS information raises performance to 77%. The paper presents
      the algorithm required to measure signal use for actual turns by realigning the
      0.2Hz GPS data, 30fps video and GIS turn events. The result is a measure that can
      be tracked over time and changes in the driver's performance can result in alerts
      to the driver, caregivers or clinicians as indication of cognitive change. A lack
      of decline can also be shared as reassurance. 

PMID- 25570807
TI  - Evaluation of lower leg swelling using EMG measured with voltage divider.
AB  - The purpose of this study is to evaluate the lower leg swelling using EMG
      measured with our new voltage divider technology, by which the internal impedance
      of lower leg can be estimated. The amplitude of EMG measured without voltage
      divider was compared to it with voltage divider. Eleven healthy subjects (24.3+/
      5.1 y.o.) participated in this study. Six female (swelling group) were asked to
      work at desk for six hours, and five male (control group) were asked to work a
      regular day. The internal impedance was calculated and calf circumference was
      measured before and after desk work. Results show that internal impedance in
      swelling group significantly decreased with increase in calf circumference, and
      our new evaluation method was proved to be effective for the evaluation of lower
      leg swelling. 

PMID- 25570808
TI  - Characterizing contact impedance, signal quality and robustness as a function of
      the cardinality and arrangement of fingers on dry contact EEG electrodes.
AB  - Continuous monitoring of patients' electroencephalography (EEG) outside of
      clinical settings will be valuable for detecting the onset of medical conditions
      such as epilepsy, as well as for enabling patients with physically disabling
      conditions like amyotrophic lateral sclerosis (ALS) to communicate using a brain
      computer interface (BCI). This requires the development of a wearable dry-contact
      EEG system that takes into account not only the signal quality but also the
      robustness of the system for everyday use. To this end, we investigate whether
      certain designs of dry electrodes lend themselves to better characteristics
      overall with respect to these factors. Five different metallic finger-based dry
      electrodes were designed and scalp electrode impedance was used to compare them
      under varying capping conditions, followed by an evaluation of how well they
      captured steady state visually evoked potentials (SSVEP). Our findings indicate
      that configurations with a relatively low density of fingers can more effectively
      penetrate through hair on the scalp and are more robust to varying conditions.
      This was confirmed to be a statistically significant observation through a one
      sided paired t-test that resulted in a p-value <; 0.004. 

PMID- 25570809
TI  - Optimising the Windkessel model for cardiac output monitoring during changes in
      vascular tone.
AB  - Algorithms for estimating cardiac output (CO) from the arterial blood pressure
      wave have been observed to be inaccurate during changes in vascular tone. Many
      such algorithms are based on the Windkessel model of the circulation. We
      investigated the optimal analytical approaches and assumptions that make up each
      algorithm during changes in vascular tone. Several analytical approaches and
      assumptions were evaluated on data from 15 critically ill patients by comparison
      with thermodilution measurements. We found that the most accurate algorithms
      assumed a constant compliance for the duration of the beat. They produced a
      percentage error of +/-31% by maintaining the compliance and outflow terms in the
      Windkessel model. For any algorithm, the following assumptions gave highest
      accuracy: (i) outflow pressure into the microcirculation is zero; (ii) end of
      systole is identified using the second derivative of pressure. None of the tested
      algorithms reached the clinically acceptable accuracy of +/-30%. 

PMID- 25570810
TI  - Audio signal analysis in combination with noncontact bio-motion data to
      successfully monitor snoring.
AB  - This paper proposes a novel algorithm for automatic detection of snoring in sleep
      by combining non-contact bio-motion data with audio data. The audio data is
      captured using low end Android Smartphones in a non-clinical environment to mimic
      a possible user-friendly commercial product for sleep audio monitoring. However
      snore detection becomes a more challenging problem as the recorded signal has
      lower quality compared to those recorded in clinical environment. To have an
      accurate classification of snore/non-snore, we first compare a range of commonly
      used features extracted from the audio signal to find the best subject
      independent features. Thereafter, bio-motion data is used to further improve the
      classification accuracy by identifying episodes which contain high amounts of
      body movements. High body movement indicates that the subject is turning,
      coughing or leaving the bed; during these instances snoring does not occur. The
      proposed algorithm is evaluated using the data recorded over 25 sessions from 7
      healthy subjects who are suspected to be regular snorers. Our experimental
      results showed that the best subject-independent features for snore/non-snore
      classification are the energy of frequency band 3150-3650 Hz, zero crossing rate
      and 1st predictor coefficient of linear predictive coding. The proposed features
      yielded an average classification accuracy of 84.35%. The introduction of bio
      motion data significantly improved the results by an average of 5.87% (p<;0.01).
      This work is the first study that successfully used bio-motion data to improve
      the accuracy of snore/non-snore classification. 

PMID- 25570811
TI  - Device and method to determine perineal artery occlusion during road bicycling.
AB  - Greater than 60 million American men who ride bicycles are at risk of developing
      erectile dysfunction. One possible reason is occlusion of the perineal arteries.
      Researchers relied on indirect methods and stationary models to study this
      problem. We developed a novel system to quantify occlusion among bicycle riders
      during a road bike ride. Our verification and validation activities show that
      this system can be safely used on human subjects to measure perineal artery
      occlusion. The method described in this paper provides a valuable tool to the
      researchers to study or to develop new solutions that alleviate this problem. The
      outcomes of these efforts will help millions of cyclists worldwide. 

PMID- 25570812
TI  - Validation of a closed-loop sensory stimulation technique for selective sleep
      restriction in mice.
AB  - Experimental manipulation of sleep in rodents is an important tool for analyzing
      the mechanisms of sleep and related disorders in humans. Sleep restriction
      systems have relied in the past on manual sensory stimulation and recently on
      more sophisticated automated means of delivering the same. The ability to monitor
      and track behavior through the electroencephalogram (EEG) and other modalities
      provides the opportunity to implement more selective sleep restriction that is
      targeted at particular stages of sleep with flexible control over their amount,
      duration, and timing. In this paper we characterize the performance of a novel
      tactile stimulation system operating in closed-loop to interrupt rapid eye
      movement (REM) sleep in mice when it is detected in real time from the EEG. Acute
      experiments in four wild-type mice over six hours showed that a reduction of over
      50% of REM sleep was feasible without affecting non-REM (NREM) sleep. The animals
      remained responsive to the stimulus over the six hour duration of the experiment.

PMID- 25570813
TI  - Flexible sixteen monopole antenna array for microwave breast cancer detection.
AB  - Radar based microwave imaging (MI) has been widely studied for breast cancer
      detection in recent times. Sensing dielectric property differences of tissues
      over a wide frequency band has been made possible by ultra-wideband (UWB)
      techniques. In this paper, a flexible, compact monopole antenna on a 100 MUm
      Kapton polyimide is designed, using a high frequency structure simulator (HFSS),
      to be in contact with biological breast tissues over the 2-5GHz frequency range.
      The antenna parameters are optimized to obtain a good impedance match over the
      required frequency range. The designed antenna size is 18mm * 18mm. Further, a
      flexible conformal 4*4 ultra-wideband antenna array, in a format similar to that
      of a bra, was developed for a radar-based breast cancer detection system. 

PMID- 25570814
TI  - Video-based early cerebral palsy prediction using motion segmentation.
AB  - Analysing distinct motion patterns that occur during infancy can be a way through
      early prediction of cerebral palsy. This analysis can only be performed by well
      trained expert clinicians, and hence can not be widespread, specially in poor
      countries. In order to decrease the need for experts, computer-based methods can
      be applied. If individual motions of different body parts are available, these
      methods could achieve more accurate results with better clinical insight. Thus
      far, motion capture systems or the like were needed in order to provide such
      data. However, these systems not only need laboratory and experts to set up the
      experiment, but they could be intrusive for the infant's motions. In this paper
      we build up our prediction method on a solution based on a single video camera,
      that is far less intrusive and a lot cheaper. First, the motions of different
      body parts are separated, then, motion features are extracted and used to
      classify infants to healthy or affected. Our experimental results show that
      visually obtained motion data allows cerebral palsy detection as accurate as
      state-of-the-art electromagnetic sensor data. 

PMID- 25570815
TI  - Unsupervised spike sorting based on discriminative subspace learning.
AB  - Spike sorting is a fundamental preprocessing step for many neuroscience studies
      which rely on the analysis of spike trains. In this paper, we present two
      unsupervised spike sorting algorithms based on discriminative subspace learning.
      The first algorithm simultaneously learns the discriminative feature subspace and
      performs clustering. It uses histogram of features in the most discriminative
      projection to detect the number of neurons. The second algorithm performs
      hierarchical divisive clustering that learns a discriminative 1-dimensional
      subspace for clustering in each level of the hierarchy until achieving almost
      unimodal distribution in the subspace. The algorithms are tested on synthetic and
      in-vivo data, and are compared against two widely used spike sorting methods. The
      comparative results demonstrate that our spike sorting methods can achieve
      substantially higher accuracy in lower dimensional feature space, and they are
      highly robust to noise. Moreover, they provide significantly better cluster
      separability in the learned subspace than in the subspace obtained by principal
      component analysis or wavelet transform. 

PMID- 25570816
TI  - Detection of epileptic seizures from single lead ECG by means of phase rectified
      signal averaging.
AB  - Epileptic seizures have a clear effect on the regulatory mechanisms of the
      autonomic nervous system, especially on the cardiac and respiratory controls.
      Changes in heart rate and respiration are well known to occur around the onset of
      the seizure. This paper studies the ECG signals recorded from patients suffering
      from epilepsy, whose ages ranged from 3 to 48 years. Both focal and generalized
      seizures are considered. Changes in cardiorespiratory control and coupling, are
      assessed using phase rectified signal averaging (PRSA), which is a technique that
      finds quasi-periodicities in noisy and non-stationary signals. A positive
      predictive value (PPV) of 86.21% with sensitivity of 100% was obtained for focal
      seizures, and a PPV of 84.3% with 93.1% sensitivity for generalized seizures.

PMID- 25570817
TI  - Single trial behavioral task classification using subthalamic nucleus local field
      potential signals.
AB  - Deep Brain Stimulation (DBS) has been a successful technique for alleviating
      Parkinson's disease (PD) symptoms especially for whom drug therapy is no longer
      efficient. Existing DBS therapy is open-loop, providing a time invariant
      stimulation pulse train that is not customized to the patient's current
      behavioral task. By customizing this pulse train to the patient's current task
      the side effects may be suppressed. This paper introduces a method for single
      trial recognition of the patient's current task using the local field potential
      (LFP) signals. This method utilizes wavelet coefficients as features and support
      vector machine (SVM) as the classifier for recognition of a selection of
      behaviors: speech, motor, and random. The proposed method is 82.4% accurate for
      the binary classification and 73.2% for classifying three tasks. These algorithms
      will be applied in a closed loop feedback control system to optimize DBS
      parameters to the patient's real time behavioral goals. 

PMID- 25570818
TI  - Discrimination of fixations and smooth pursuit movements in high-speed eye
      tracking data.
AB  - A novel three-stage algorithm for detection of fixations and smooth pursuit
      movements in high-speed eye-tracking data is proposed. In the first stage, a
      segmentation based on the directionality of the data is performed. In the second
      stage, four spatial features are computed from the data in each segment. Finally,
      data are classified into fixations and smooth pursuit movements based on a
      combination of the spatial features and the properties of neighboring segments.
      The algorithm is evaluated under the assumption that the intersaccadic intervals
      represent fixations in data recorded when viewing images, and mainly smooth
      pursuit movements in data recorded when viewing moving dots. The results show
      that the algorithm is able to detect 94.3% of the fixations for image stimuli,
      compared to a previous algorithm with 80.4% detected fixations. For moving dot
      stimuli the proposed algorithm detects 86.7% smooth pursuit movements compared to
      68.0% for the previous algorithm. 

PMID- 25570819
TI  - Single trial P300 detection in children using expert knowledge and SOM.
AB  - Preliminary results of an automatic system for single trial P300 visual evoked
      potential events detection are presented. For each single trial P300, several
      candidate events were generated, and then filtered, using 3 wave features. The
      surviving candidate events were fed into a SOM-based classifier. A context filter
      was applied before the final output. No stationary condition of the P300 is
      involved in the algorithms. Recordings of 27 assessment sessions, each with 120
      trials, were visually inspected by experts to identify and mark the P300 events,
      which was accomplished in about one third of the trials. The dataset was divided
      in training (18) and testing (9) subsets. The system identifies the initial and
      end times of the P300; it obtained a sensitivity of 53.9%, a specificity of 64.0%
      and an accuracy of 61.2% in the testing dataset. 

PMID- 25570820
TI  - Characterization of the autonomic system during the cyclic alternating pattern of
      sleep.
AB  - Evaluation of the RR variability was carried out during the Cyclic Alternating
      Pattern (CAP) in sleep. CAP is a central phenomenon formed by short events called
      A-phases that break basal electroencephalogram (EEG) oscillations of the sleep
      stages. A-phases are classified in three types (A1, A2 and A3) based on the EEG
      desynchronization during A-phase. However, the relation of A-phases with other
      systems, such as cardiovascular system, is unclear and a deep analysis is
      required. For the study, six patients with Nocturnal Front Lobe Epilepsy (NFLE)
      and other six healthy controls patients underwent whole night polysomnographic
      recordings with CAP and hypnogram annotations. Amplitude reduction and time delay
      of the RR intervals minimum with respect to A-phases onset were computed. In
      addition, the same process was computed over randomly chosen RR interval segments
      during the NREM sleep for further comparison. The results suggest that the onset
      of the A-phases is correlated with a significative increase of the heart rate
      that peaks at around 4s after the Aphase onset, independently of the A-phase
      subtype. 

PMID- 25570821
TI  - Comparison of methods for determining pulse arrival time from Doppler and
      photoplethysmography signals.
AB  - The aim of this study was to compare three foot-finding methods applied to
      ultrasound Doppler and photoplethysmographic (PPG) signals: maximum 1st
      derivative, maximum 2nd derivative and an 'intersecting tangents' method. The
      pulse arrival times of each method were compared. Also the precision of each
      method was evaluated by comparing instantaneous cardiac periods derived using
      each method from simultaneous Doppler and PPG with a reference measurement: the R
      R interval calculated from a simultaneously recorded ECG. The results show that
      the maximum 1st derivative method produced significantly larger pulse arrival
      times than the other two methods. The intersecting tangents method produced
      greatest precision for cardiac periods compared with ECG than maximum 1st or 2nd
      derivatives for both Doppler (r(2) = 0.975) and PPG (r(2) = 0.987) signals.

PMID- 25570822
TI  - Estimation of bilateral asynchrony between diaphragm mechanomyographic signals in
      patients with chronic obstructive pulmonary disease.
AB  - The aim of the present study was to measure bilateral asynchrony in patients
      suffering from Chronic Obstructive Pulmonary Disease (COPD) performing an
      incremental inspiratory load protocol. Bilateral asynchrony was estimated by the
      comparison of respiratory movements derived from diaphragm mechanomyographic
      (MMGdi) signals, acquired by means of capacitive accelerometers placed on left
      and right sides of the rib cage. Three methods were considered for asynchrony
      evaluation: Lissajous figure, Hilbert transform and Motto's algorithm. Bilateral
      asynchrony showed an increase at 20, 40 and 60% (values of normalized inspiratory
      pressure by their maximum value reached in the last inspiratory load) while the
      very severe group showed an increase at 20, 40, 80, and 100 % during the
      protocol. These increments in the phase's shift can be due to an increase of the
      inspiratory load along the protocol, and also as a consequence of distress and
      fatigue. In summary, this work evidenced the capability to estimate bilateral
      asynchrony in COPD patients. These preliminary results also showed that the use
      of capacitive accelerometers can be a suitable sensor for recording of
      respiratory movement and evaluation of asynchrony in COPD patients.

PMID- 25570823
TI  - Towards continuous monitoring of pulse rate in neonatal intensive care unit with
      a webcam.
AB  - We describe a novel method to monitor pulse rate (PR) on a continuous basis of
      patients in a neonatal intensive care unit (NICU) using videos taken from a high
      definition (HD) webcam. We describe algorithms that determine PR from
      videoplethysmographic (VPG) signals extracted from multiple regions of interest
      (ROI) simultaneously available within the field of view of the camera where
      cardiac signal is registered. We detect motion from video images and compensate
      for motion artifacts from each ROI. Preliminary clinical results are presented on
      8 neonates each with 30 minutes of uninterrupted video. Comparisons to hospital
      equipment indicate that the proposed technology can meet medical industry
      standards and give improved patient comfort and ease of use for practitioners
      when instrumented with proper hardware. 

PMID- 25570824
TI  - Respiratory rate estimation from the oscillometric waveform obtained from a non
      invasive cuff-based blood pressure device.
AB  - The presence of respiratory activity in the electrocardiogram (ECG), the pulse
      oximeter's photoplethysmo-graphic and continuous arterial blood pressure signals
      is a well-documented phenomenon. In this paper, we demonstrate that such
      information is also present in the oscillometric signal acquired from automatic
      non-invasive blood pressure monitors, and may be used to estimate the vital sign
      respiratory rate (RR). We propose a novel method that combines the information
      from the two respiratory-induced variations (frequency and amplitude) via
      frequency analysis to both estimate RR and eliminate estimations considered to be
      unreliable because of poor signal quality. The method was evaluated using data
      acquired from 40 subjects containing ECG, respiration and blood pressure
      waveforms, the latter acquired using an in-house built blood pressure device that
      is able to connect to a mobile phone. Results demonstrated a good RR estimation
      accuracy of our method when compared to the reference values extracted from the
      reference respiration waveforms (mean absolute error of 2.69 breaths/min), which
      is comparable to existing methods in the literature that extract RR from other
      physiological signals. The proposed method has been implemented in Java on the
      Android device for use in an mHealth platform. 

PMID- 25570825
TI  - Computing network-based features from physiological time series: application to
      sepsis detection.
AB  - Sepsis is a systemic deleterious host response to infection. It is a major
      healthcare problem that affects millions of patients every year in the intensive
      care units (ICUs) worldwide. Despite the fact that ICU patients are heavily
      instrumented with physiological sensors, early sepsis detection remains
      challenging, perhaps because clinicians identify sepsis by using static scores
      derived from bed-side measurements individually, i.e., without systematically
      accounting for potential interactions between these signals and their dynamics.
      In this study, we apply network-based data analysis to take into account
      interactions between bed-side physiological time series (PTS) data collected in
      ICU patients, and we investigate features to distinguish between sepsis and non
      sepsis conditions. We treated each PTS source as a node on a graph and we
      retrieved the graph connectivity matrix over time by tracking the correlation
      between each pair of sources' signals over consecutive time windows. Then, for
      each connectivity matrix, we computed the eigenvalue decomposition. We found
      that, even though raw PTS measurements may have indistinguishable distributions
      in non-sepsis and early sepsis states, the median /I of the eigenvalues computed
      from the same data is statistically different (p <; 0.001) in the two states and
      the evolution of /I may reflect the disease progression. Although preliminary,
      these findings suggest that network-based features computed from continuous PTS
      data may be useful for early sepsis detection. 

PMID- 25570826
TI  - Classification of finger extension and flexion of EMG and Cyberglove data with
      modified ICA weight matrix.
AB  - This paper reports the classification of finger flexion and extension of surface
      Electromyography (EMG) and Cyberglove data using the modified Independent
      Component Analysis (ICA) weight matrix. The finger flexion and extension data are
      processed through Principal Component Analysis (PCA), and next separated using
      modified ICA for each individual with customized weight matrix. The extension and
      flexion features of sEMG and Cyberglove (extracted from modified ICA) were
      classified using Linear Discriminant Analysis (LDA) with near 90% classification
      accuracy. The applications of this study include Human Computer Interface (HCI),
      virtual reality and neural prosthetics. 

PMID- 25570827
TI  - Low complexity underdetermined blind source separation system architecture for
      emerging remote healthcare applications.
AB  - In this paper, we have proposed a low complexity architecture for the Under
      determined Blind Source Separation (UBSS) algorithm targeting remote healthcare
      applications. UBSS algorithm, departing from the typical BSS convention-equal
      number of the sources and sensors present, which is of tremendous interest in the
      field of Biomedical signal processing especially for remote health care
      applications. Since such applications are constrained by the on-chip area and
      power consumption limitation due to the battery backup, a low complexity
      architecture needs to be formulated. In this paper, firstly we have introduced
      UBSS architecture, followed by the identification of the most computationally
      intensive module N-point Discrete Hilbert Transform (DHT) and finally proposed a
      low complexity DHT architecture design to make the entire UBSS architecture
      suitable for such resource constrained applications. The proposed DHT
      architecture implementation and experimental comparison results show that the
      proposed design saves 50.28%, 48.40% and 46.27% on-chip area and 53.25%, 48.01%
      and 45.95% power consumption when compared to the state of the art method for N =
      32, 64 and 128 respectively. Furthermore the proposed DHT architecture works for
      N = 2m point, but the state of art architecture works for N = 4m point, where m
      is an integer. 

PMID- 25570828
TI  - Higher dimensional analysis shows reduced dynamism of time-varying network
      connectivity in schizophrenia patients.
AB  - Assessments of functional connectivity between brain networks is a fixture of
      resting state fMRI research. Until very recently most of this work proceeded from
      an assumption of stationarity in resting state network connectivity. In the last
      few years however, interest in moving beyond this simplifying assumption has
      grown considerably. Applying group temporal independent component analysis (tICA)
      to a set of time-varying functional network connectivity (FNC) matrices derived
      from a large multi-site fMRI dataset (N=314; 163 healthy, 151 schizophrenia
      patients), we obtain a set of five basic correlation patterns (component spatial
      maps (SMs)) from which observed FNCs can be expressed as mutually independent
      linear combinations, i.e., the coefficient on each SM in the linear combination
      is maximally independent of the others. We study dynamic properties of network
      connectivity as they are reflected in this five-dimensional space, and report
      stark differences in connectivity dynamics between schizophrenia patients and
      healthy controls. We also find that the most important global differences in FNC
      dynamism between patient and control groups are replicated when the same
      dynamical analysis is performed on sets of correlation patterns obtained from
      either PCA or spatial ICA, giving us additional confidence in the results. 

PMID- 25570829
TI  - Validating the effect of muscle artifact suppression in localizing focal
      epilepsy.
AB  - Source localization of an epileptic seizure is becoming an important diagnostic
      tool in pre-surgical evaluation of epileptic patients. However, for localizing
      the epileptogenic zone precisely, the epileptic activity needs to be isolated
      from other activities that are not related to the epileptic source. In this
      study, we aim at an investigation of the effect of muscle artifact suppression by
      using a low-pass filter (LPF), independent component analysis (ICA), and a
      combination of ICA-LPF prior to source localization in focal epilepsy. These
      techniques were applied on the EEG data obtained from a left-temporal lobe
      epileptic patient by artificially contaminating the isolated spike interval,
      present in the four left-temporal electrodes, with a muscle artifact. The results
      show that the muscle artifact was fully suppressed. Applying the dipole and
      current-density reconstruction (CDR) source-analysis algorithms on the filtered
      data, we were able to identify the location of the epileptogenic zone similar to
      that of the original undistorted data. 

PMID- 25570830
TI  - Online recursive independent component analysis for real-time source separation
      of high-density EEG.
AB  - Online Independent Component Analysis (ICA) algorithms have recently seen
      increasing development and application across a range of fields, including
      communications, biosignal processing, and brain-computer interfaces. However,
      prior work in this domain has primarily focused on algorithmic proofs of
      convergence, with application limited to small 'toy' examples or to relatively
      low channel density EEG datasets. Furthermore, there is limited availability of
      computationally efficient online ICA implementations, suitable for real-time
      application. This study describes an optimized online recursive ICA algorithm
      (ORICA), with online recursive least squares (RLS) whitening, for blind source
      separation of high-density EEG data. It is implemented as an online-capable
      plugin within the open-source BCILAB (EEGLAB) framework. We further derive and
      evaluate a block-update modification to the ORICA learning rule. We demonstrate
      the algorithm's suitability for accurate and efficient source identification in
      high density (64-channel) realistically-simulated EEG data, as well as real 61
      channel EEG data recorded by a dry and wearable EEG system in a cognitive
      experiment. 

PMID- 25570831
TI  - An efficient ASIC implementation of 16-channel on-line recursive ICA processor
      for real-time EEG system.
AB  - This is a proposal for an efficient very-large-scale integration (VLSI) design,
      16-channel on-line recursive independent component analysis (ORICA) processor
      ASIC for real-time EEG system, implemented with TSMC 40 nm CMOS technology. ORICA
      is appropriate to be used in real-time EEG system to separate artifacts because
      of its highly efficient and real-time process features. The proposed ORICA
      processor is composed of an ORICA processing unit and a singular value
      decomposition (SVD) processing unit. Compared with previous work [1], this
      proposed ORICA processor has enhanced effectiveness and reduced hardware
      complexity by utilizing a deeper pipeline architecture, shared arithmetic
      processing unit, and shared registers. The 16-channel random signals which
      contain 8-channel super-Gaussian and 8-channel sub-Gaussian components are used
      to analyze the dependence of the source components, and the average correlation
      coefficient is 0.95452 between the original source signals and extracted ORICA
      signals. Finally, the proposed ORICA processor ASIC is implemented with TSMC 40
      nm CMOS technology, and it consumes 15.72 mW at 100 MHz operating frequency. 

PMID- 25570832
TI  - Automatic selection of epileptic independent fMRI components.
AB  - EEG-correlated fMRI analysis has proven to be useful in localizing regions of
      BOLD activation related to epileptic activity. However, as EEG does not always
      provide reliable information, purely fMRI-based data-driven techniques are
      invaluable. Recently, we have shown that independent component analysis (ICA) can
      extract sources related to the epileptic network even in such EEG-negative cases
      [1]. Moreover, these sources were shown to be informative with respect to the
      seizure onset zone (SOZ). In order to utilize this concept in clinical practice
      in a prospective manner, this work aims at developing an automatic technique for
      selecting the epileptic sources. The proposed approach applies a cascade of two
      classifiers. In the first step artifact related sources are discarded. In the
      second step the sources are characterized by four discriminative features and
      epileptic sources are selected from among other BOLD-related components. Our
      technique reaches a promising 77% specificity and provides concordant sources
      with the EEG-correlated fMRI activation maps or with the SOZ in 71% of the cases.

PMID- 25570833
TI  - Comparison of JADE and canonical correlation analysis for ECG de-noising.
AB  - This paper explores differences between two methods for blind source separation
      within frame of ECG de-noising. First method is joint approximate diagonalization
      of eigenmatrices, which is based on estimation of fourth order cross-cummulant
      tensor and its diagonalization. Second one is the statistical method known as
      canonical correlation analysis, which is based on estimation of correlation
      matrices between two multidimensional variables. Both methods were used within
      method, which combines the blind source separation algorithm with decision tree.
      The evaluation was made on large database of 382 long-term ECG signals and the
      results were examined. Biggest difference was found in results of 50 Hz power
      line interference where the CCA algorithm completely failed. Thus main power of
      CCA lies in estimation of unstructured noise within ECG. JADE algorithm has
      larger computational complexity thus the CCA perfomed faster when estimating the
      components.

PMID- 25570834
TI  - ICA-based reduction of electromyogenic artifacts in EEG data: comparison with and
      without EMG data.
AB  - Analysis of electroencephalography (EEG) recorded during movement is often
      aggravated or even completely hindered by electromyogenic artifacts. This is
      caused by the overlapping frequencies of brain and myogenic activity and the
      higher amplitude of the myogenic signals. One commonly employed computational
      technique to reduce these types of artifacts is Independent Component Analysis
      (ICA). ICA estimates statistically independent components (ICs) that, when
      linearly combined, closely match the input (sensor) data. Removing the ICs that
      represent artifact sources and re-mixing the sources returns the input data with
      reduced noise activity. ICs of real-world data are usually not perfectly
      separated, actual sources, but a mixture of these sources. Adding additional
      input signals, predominantly generated by a single IC that is already part of the
      original sensor data, should increase that IC's separability. We conducted this
      study to evaluate this concept for ICA-based electromyogenic artifact reduction
      in EEG using EMG signals as additional inputs. To acquire the appropriate data we
      worked with nine human volunteers. The EEG and EMG were recorded while the study
      volunteers performed seven exercises designed to produce a wide range of
      representative myogenic artifacts. To evaluate the effect of the EMG signals we
      estimated the sources of each dataset once with and once without the EMG data.
      The ICs were automatically classified as either 'myogenic' or 'non-myogenic'. We
      removed the former before back projection. Afterwards we calculated an objective
      measure to quantify the artifact reduction and assess the effect of including EMG
      signals. Our study showed that the ICA-based reduction of electromyogenic
      artifacts can be improved by including the EMG data of artifact-inducing muscles.
      This approach could prove beneficial for locomotor disorder research, brain
      computer interfaces, neurofeedback, and most other areas where brain activity
      during movement has to be analyzed. 

PMID- 25570835
TI  - Noninvasive in vivo imaging of oxygen metabolic rate in the retina.
AB  - Precise and noninvasive measurement of retinal oxygen metabolic rate is important
      for retinal pathological investigations as well as retinal disease detection,
      which has not been achieved until recently. Here, we quantified retinal oxygen
      metabolic rate in rats by combining photoacoustic ophthalmoscopy with spectral
      domain-optical coherence tomography. We employed multi-wavelength photoacoustic
      ophthalmoscopy for oxygen saturation measurement and applied dual-ring scanning
      Doppler spectral domain-optical coherence tomography to image retinal blood flow.
      With retinal oxygen saturation and blood flow being measured, we determined the
      retinal oxygen metabolic rate in a typical rat to be 373.41 +/- 88.04 ng/minute. 

PMID- 25570836
TI  - A hierarchical framework for estimating neuroretinal rim area using 3D spectral
      domain optical coherence tomography (SD-OCT) optic nerve head (ONH) images of
      healthy and glaucoma eyes.
AB  - Glaucoma is a chronic neurodegenerative disease characterized by loss of retinal
      ganglion cells, resulting in distinctive changes in the optic nerve head (ONH)
      and retinal nerve fiber layer (RNFL). Important advances in technology for non
      invasive imaging of the eye have been made providing quantitative tools to
      measure structural changes in ONH topography, a crucial step in diagnosing and
      monitoring glaucoma. 3D spectral domain optical coherence tomography (SD-OCT), an
      optical imaging technique, has been commonly used to discriminate glaucomatous
      from healthy subjects. In this paper, we present a new approach for locating the
      Bruch's membrane opening BMO and then estimating the optic disc size and rim area
      of 3D Spectralis SD-OCT images. To deal with the overlapping of the Bruch's
      membrane BM layer and the border tissue of Elschnig due to the poor image
      resolution, we propose the use of image deconvolution approach to separate these
      layers. To estimate the optic disc size and rim area, we propose the use of a new
      regression method based on the artificial neural network principal component
      analysis (ANN-PCA), which allows us to model irregularity in the BMO estimation
      due to scan shifts and/or poor image quality. The diagnostic accuracy of rim
      area, and rim to disc area ratio is compared to the diagnostic accuracy of global
      RNFL thickness measurements provided by two commercially available SD-OCT devices
      using receiver operating characteristic curve analyses. 

PMID- 25570837
TI  - An automated 3D registration method for optical coherence tomography volumes.
AB  - Optical coherence tomography (OCT) is able to provide high resolution volumetric
      data for biological tissues. However, the field of view (FOV) of OCT is sometimes
      smaller than the field of interest, which limits the clinical application of OCT.
      One way to overcome the drawback is to stitch multiple 3D volumes. In this paper,
      we propose a novel method to register multiple overlapped volumetric OCT data
      into a single volume. The relative positions of overlapped volumes were estimated
      on en face plane and at depth. On en face plane, scale invariant feature
      transform (SIFT) was implemented to extract the keypoints in each volume. Based
      on the invariant features, volumes were paired through keypoint matching. Then,
      we formulated the relationship between paired offsets and absolute positions as a
      linear model and estimated the centroid of each volume using least square method.
      Moreover, we calibrated the depth displacement in each paired volume and aligned
      the z coordinates of volumes globally. The algorithm was validated through
      stitching multiple volumetric OCT datasets of human cervix tissue and of swine
      heart. The experimental results demonstrated that our method is capable of
      visualizing biological samples over a wider FOV, which enhances the investigation
      of tissue structure such as fiber orientation. 

PMID- 25570838
TI  - Adaptive-optics optical coherence tomography processing using a graphics
      processing unit.
AB  - Graphics processing units are increasingly being used for scientific computing
      for their powerful parallel processing abilities, and moderate price compared to
      super computers and computing grids. In this paper we have used a general purpose
      graphics processing unit to process adaptive-optics optical coherence tomography
      (AOOCT) images in real time. Increasing the processing speed of AOOCT is an
      essential step in moving the super high resolution technology closer to clinical
      viability. 

PMID- 25570839
TI  - Measuring absolute microvascular blood flow in cortex using visible-light optical
      coherence tomography.
AB  - Understanding regulating mechanisms of cerebral blood flow (CBF) is important for
      clinical diagnosis and biomedical researches. We demonstrate here that phase
      sensitive Doppler optical coherence tomography is able to measure absolute CBF in
      mouse visual cortex in vivo when working in the visible-light spectral range.
      Both temporal and spatial profile of regional CBF variations can be resolved. We
      further assessed the accuracy of our method by in vitro experiments, which showed
      great consistency between the measured values and controlled ones. Finally, we
      enhanced the contrast of blood vessels to generate an angiogram showing great
      details of mouse cortical microvasculature. 

PMID- 25570840
TI  - Angle closure glaucoma detection using fractal dimension index on SS-OCT images.
AB  - Optical coherence tomography (OCT) is a high resolution, rapid and non-invasive
      screening tool for angle closure glaucoma. In this paper, we propose a new
      strategy for automatic and landmark invariant quantification of the anterior
      chamber angle of the eye using swept source optical coherence tomography (SS-OCT)
      images. Seven hundred and eight swept source optical coherence tomography SS-OCT
      images from 148 patients with average age of (59.48 +/- 8.97) were analyzed in
      this study. The angle structure is measured by fractal dimension (FD) analysis to
      quantify the complexity or changes of angle recess. We evaluated the FD index
      with biometric parameters for classification of open angle and angle closure
      glaucoma. The proposed fractal dimension index gives a better representation of
      the angle configuration for capturing the nature of the angle dynamics involved
      in different forms of open and closed angle glaucoma (average FD (standard
      deviation): 1.944 (0.045) for open and 1.894 (0.043) for closed angle). It showed
      that the proposed approach has promising potential to become a computer aided
      diagnostic tool for angle closure glaucoma (ACG) disease. 

PMID- 25570841
TI  - Combination of FMRI-SMRI-EEG data improves discrimination of schizophrenia
      patients by ensemble feature selection.
AB  - Multimodal brain imaging data fusion is a scientifically interesting and
      clinically important topic; however, there is relatively little work on N-way
      data fusion. In this paper, we applied multi-set canonical correlation analysis
      (MCCA) to combine data of resting state fMRI, EEG and sMRI, in order to elucidate
      the abnormalities that underlie schizophrenia patients and also covary across
      multiple modalities. We also tested whether the identified group-discriminative
      components can be used for feature selection in group classification. MCCA is
      demonstrated to be an effective feature selection technique, especially in
      multimodal fusion. We also proposed an ensemble feature selection scheme by
      combining two sample t-test, MCCA and support vector machine with recursive
      feature elimination (SVM-RFE), resulting in optimal group-discriminating features
      for each modality. Finally, we compared the classifying power between two groups
      based on the above selected features via 7 modality-combinations. Results show
      that the fMRI-sMRI-EEG combination derives the best classification accuracy in
      training (91%) and predication rate (100%) in testing data, validating the
      effectiveness and advantages of multimodal fusion in discriminating
      schizophrenia. 

PMID- 25570842
TI  - Anisotropic anomalous diffusion filtering applied to relaxation time estimation
      in magnetic resonance imaging.
AB  - Relaxometry mapping is a quantitative modality in magnetic resonance imaging
      (MRI) widely used in neuroscience studies. Despite its relevance and utility,
      voxel measurement of relaxation time in relaxometry MRI is compromised by noise
      that is inherent to MRI modality and acquisition hardware. In order to enhance
      signal to noise ratio (SNR) and quality of relaxometry mapping we propose
      application of anisotropic anomalous diffusion (AAD) filter that is consistent
      with inhomogeneous complex media. Here we evaluated AAD filter in comparison to
      two usual spatial filters: Gaussian and non local means (NLM) filters applied to
      real and simulated T2 relaxometry image sequences. The results demonstrate that
      AAD filter is comparatively more efficient in noise reducing and maintaining the
      image structural edges. AAD shows to be a robust and reliable spatial filter for
      brain image relaxometry. 

PMID- 25570843
TI  - Tensor-product kernel-based representation encoding joint MRI view similarity.
AB  - To support 3D magnetic resonance image (MRI) analysis, a marginal image
      similarity (MIS) matrix holding MR inter-slice relationship along every axis view
      (Axial, Coronal, and Sagittal) can be estimated. However, mutual inference from
      MIS view information poses a difficult task since relationships between axes are
      nonlinear. To overcome this issue, we introduce a Tensor-Product Kernel-based
      Representation (TKR) that allows encoding brain structure patterns due to patient
      differences, gathering all MIS matrices into a single joint image similarity
      framework. The TKR training strategy is carried out into a low dimensional
      projected space to get less influence of voxel-derived noise. Obtained results
      for classifying the considered patient categories (gender and age) on real MRI
      database shows that the proposed TKR training approach outperforms the
      conventional voxel-wise sum of squared differences. The proposed approach may be
      useful to support MRI clustering and similarity inference tasks, which are
      required on template-based image segmentation and atlas construction. 

PMID- 25570844
TI  - Multi dose computed tomography image fusion based on hybrid sparse methodology.
AB  - With the increasing utilization of X-ray Computed Tomography (CT) in medical
      diagnosis, obtaining higher quality image with lower exposure to radiation has
      become a highly challenging task in image processing. In this paper, a novel
      sparse fusion algorithm is proposed to address the problem of lower Signal to
      Noise Ratio (SNR) in low dose CT images. Initial fused image is obtained by
      combining low dose and medium dose images in sparse domain, utilizing the Dual
      Tree Complex Wavelet Transform (DTCWT) dictionary which is trained by high dose
      image. And then, the strongly focused image is obtained by determining the pixels
      of source images which have high similarity with the pixels of the initial fused
      image. Final denoised image is obtained by fusing strongly focused image and
      decomposed sparse vectors of source images, thereby preserving the edges and
      other critical information needed for diagnosis. This paper demonstrates the
      effectiveness of the proposed algorithm both quantitatively and qualitatively. 

PMID- 25570845
TI  - Image enhancement and space-variant color reproduction method for endoscopic
      images using adaptive sigmoid function.
AB  - This paper presents an image enhancement and space-variant color reproduction
      method based on adaptive sigmoid function for endoscopic image. At first, using
      YCBCR conversion matrix, the color image is separated into luminance and
      chrominance components. The adaptive sigmoid function with two controlling
      parameters is applied on the uniformly distributed luminance pixels. The space
      variant color reproduction generates new chrominance components by transferring
      and modifying old chrominance based on texture information. Finally, new
      luminance and chrominance components are converted into RGB color image. The
      proposed method highlights some of the tissue and vascular characteristics as
      well as pit patterns in lesion and polyp. The performance of the proposed scheme
      is compared with other related methods in terms of image quality, focus value,
      efficiency of color reproduction and statistic of visual representation. 

PMID- 25570846
TI  - Speckle reduction by phase-based weighted least squares.
AB  - Although ultrasonography has been widely used in clinical applications, the
      doctor suffers great difficulties in diagnosis due to the artifacts of ultrasound
      images, especially the speckle noise. This paper proposes a novel framework for
      speckle reduction by using a phase-based weighted least squares optimization. The
      proposed approach can effectively smooth out speckle noise while preserving the
      features in the image, e.g., edges with different contrasts. To this end, we
      first employ a local phase-based measure, which is theoretically intensity
      invariant, to extract the edge map from the input image. The edge map is then
      incorporated into the weighted least squares framework to supervise the
      optimization during despeckling, so that low contrast edges can be retained while
      the noise has been greatly removed. Experimental results in synthetic and
      clinical ultrasound images demonstrate that our approach performs better than
      state-of-the-art methods. 

PMID- 25570847
TI  - Reduction of water diffusion coefficient with increased engineered cartilage
      matrix growth observed using MRI.
AB  - Non-destructive monitoring of tissue-engineered cartilage growth is needed to
      optimize growth conditions, but extracting quantitative biomarkers of
      extracellular matrix development remains a technical challenge. MRI provides a
      non-invasive way to obtain a three dimensional map of growing tissue where the
      image contrast is based on tissue water relaxation times and the apparent
      diffusion coefficient (ADC). In this study, bovine chondrocytes were seeded in
      alginate beads (0, 1, 2, and 4 million cells/ml) and the ADC was measured weekly
      using diffusion-weighted MRI at 14.1 T over a one-month incubation period. Two
      groups of tissue-engineering constructs were created: one with ascorbic acid
      (vitamin C) added as a vitamin cofactor to increase collagen synthesis, and
      another with no added ascorbic acid. When normalized to the control beads without
      chondrocytes, the ADC was found to monotonically fall with incubation time
      (decreasing by up to 40% at 4 weeks), and with the administration of vitamin C.
      These results reflect the expected development of the extracellular matrix in the
      tissue-engineered constructs. We conclude that the normalized ADC is a potential
      biomarker for characterizing engineered cartilage tissue growth. 

PMID- 25570848
TI  - Osteoinductive calcium phosphate clay nanoparticle bone cements (CPCs) with
      enhanced mechanical properties.
AB  - Calcium phosphate cements (CPCs) with osteoconductive properties are limited in
      their applications because of their poor mechanical properties. This study
      investigated the additive effect of Dexamethasone-doped Halloysite Nanotubes
      (HNTs on the mechanical properties of CPCs. HNTs are nanosized tubes with alumino
      silicate composition. Physico-chemical properties, cytocompatability and cellular
      functionality of the nanocomposites were assayed. Results suggest that these
      nanoenhanced composites have a huge potential to broaden the applications of
      CPCs.

PMID- 25570849
TI  - Design and evaluation of a nanoenhanced anti-infective calcium phosphate bone
      cements.
AB  - Post-operative complications due to infections are the most common problems that
      occur following dental and orthopedic implant surgeries and bone repair
      procedures. Preventing post-surgical infections is therefore a critical need that
      current polymethylmethacrylate (PMMA) bone cement fail to address. Calcium
      phosphate cements (CPCs) are unique in their ability to crystallize calcium and
      phosphate salts into hydroxyapatite (HA) and hence is naturally osteoconductive.
      Due to its low mechanical strength its use in implant fixation and bone repair is
      limited to non-load bearing applications. The present work describes a new and
      novel antibiotic-doped clay nanotube CPC composite with enhanced mechanical
      properties as well as sustained release properties. 

PMID- 25570850
TI  - A potential translational approach for bone tissue engineering through
      endochondral ossification.
AB  - Bone defect repair is a significant clinical challenge in orthopedic surgery.
      Despite tremendous efforts, the majority of the current bone tissue engineering
      strategies depend on bone formation via intramembranous ossification (IO), which
      often results in poor vascularization and limited-area bone regeneration.
      Recently, there has been increasing interest in exploring bone regeneration
      through a cartilage-mediated process similar to endochondral ossification (EO).
      This method is advantageous because long bones are originally developed through
      EO and moreover, vascularization is an inherent step of this process. Therefore,
      it may be possible to effectively employ the EO method for the repair and
      regeneration of large and segmental bone defects. Although a number of studies
      have demonstrated engineered bone formation through EO, there are no approaches
      aiming for their clinical translation. In this study, we propose a strategy
      modeled after the U.S. Food and Drug Administration (FDA) approved autologus
      chondrocyte implantation (ACI) procedure. In its implementation, we concentrated
      human bone marrow aspirate via a minimally manipulated process and demonstrated
      the potential of human bone marrow derived cells for in vitro pre-cartilage
      template formation and bone regeneration in vivo.

PMID- 25570851
TI  - Magnetic resonance spectroscopy and imaging can differentiate between engineered
      bone and engineered cartilage.
AB  - In the situation when both cartilage and its underlying bone are damaged,
      osteochondral tissue engineering is being developed to provide a solution. In
      such cases, the ability to non-invasively monitor and differentiate the
      development of both cartilage and bone tissues is important. Nuclear magnetic
      resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) have been
      widely used to non-invasively assess tissue-engineered cartilage and tissue
      engineered bone. The purpose of this work is to assess differences in MR
      properties of tissue-engineered bone and tissue-engineered cartilage generated
      from the same cell-plus-scaffold combination at the early stage of tissue growth.
      We developed cartilage and bone tissue constructs by seeding human marrow stromal
      cells (HMSCs, 2 million/ml) in 1:1 collagen/chitosan gel for four weeks. The
      chondrogenic or osteogenic differentiation of cells was directed with the aid of
      a culture medium containing chondrogenic or osteogenic growth factors,
      respectively. The proton and sodium NMR and waterproton T1, T2 and diffusion MRI
      experiments were performed on these constructs and the control collagen/chitosan
      gel using a 9.4 T ((1)H freq. = 400 MHz) and a 11.7 T ((1)H freq. = 500 MHz) NMR
      spectrometers. In all cases, the development of bone and cartilage was found to
      be clearly distinguishable using NMR and MRI. We conclude that MRS and MRI are
      powerful tools to assess growing osteochondral tissue regeneration. 

PMID- 25570852
TI  - True MRI assessment of stem cell chondrogenesis in a tissue engineered matrix.
AB  - Developing a non-invasive method to monitor the growth of tissue-engineered
      cartilage is of utmost importance for tracking the progress and predicting the
      success or failure of tissue-engineering approaches. Magnetic Resonance Imaging
      (MRI) is a leading non-invasive technique suitable for follow-through in
      preclinical and clinical stages. As complex tissue-engineering approaches are
      being developed for cartilage tissue engineering, it is important to develop
      strategies for true non-invasive MRI monitoring that can take into account
      contributions of the scaffold, cells and extracellular matrix (ECM) using MR
      parameters. In the current study, we present the preliminary MRI assessment of
      chondrogenic differentiation of human bone marrow derived stem cells seeded onto
      a specially designed osteochondral matrix system. We performed water relaxation
      times (T1 and T2) MRI measurements at 7, 14 and 28 days after cell seeding. The
      MRI experiments were performed for the tissue-engineered cartilage as well as for
      acellular scaffolds. We identified that the contribution of the scaffold is the
      dominant contribution in MR parameters of engineered cartilage and that it
      hinders observation of the tissue growth. An attempt is made to filter out this
      contribution, for the first time, in order to make a true observation of tissue
      growth using MRI. 

PMID- 25570854
TI  - Combining image processing and modeling to generate traces of beta-strands from
      cryo-EM density images of beta-barrels.
AB  - Electron cryo-microscopy (Cryo-EM) technique produces 3-dimensional (3D) density
      images of proteins. When resolution of the images is not high enough to resolve
      the molecular details, it is challenging for image processing methods to enhance
      the molecular features. beta-barrel is a particular structure feature that is
      formed by multiple beta-strands in a barrel shape. There is no existing method to
      derive beta-strands from the 3D image of a beta-barrel at medium resolutions. We
      propose a new method, StrandRoller, to generate a small set of possible beta
      traces from the density images at medium resolutions of 5-10A. StrandRoller has
      been tested using eleven beta-barrel images simulated to 10A resolution and one
      image isolated from the experimentally derived cryo-EM density image at 6.7A
      resolution. StrandRoller was able to detect 81.84% of the beta-strands with an
      overall 1.5A 2-way distance between the detected and the observed beta-traces, if
      the best of fifteen detections is considered. Our results suggest that it is
      possible to derive a small set of possible beta-traces from the beta-barrel cryo
      EM image at medium resolutions even when no separation of the beta-strands is
      visible in the images. 

PMID- 25570853
TI  - BSSV: Bayesian based somatic structural variation identification with whole
      genome DNA-seq data.
AB  - High coverage whole genome DNA-sequencing enables identification of somatic
      structural variation (SSV) more evident in paired tumor and normal samples.
      Recent studies show that simultaneous analysis of paired samples provides a
      better resolution of SSV detection than subtracting shared SVs. However,
      available tools can neither identify all types of SSVs nor provide any rank
      information regarding their somatic features. In this paper, we have developed a
      Bayesian framework, by integrating read alignment information from both tumor and
      normal samples, called BSSV, to calculate the significance of each SSV. Tested by
      simulated data, the precision of BSSV is comparable to that of available tools
      and the false negative rate is significantly lowered. We have also applied this
      approach to The Cancer Genome Atlas breast cancer data for SSV detection. Many
      known breast cancer specific mutated genes like RAD51, BRIP1, ER, PGR and PTPRD
      have been successfully identified. 

PMID- 25570856
TI  - Structure of collagen-glycosaminoglycan matrix and the influence to its integrity
      and stability.
AB  - Glycosaminoglycan (GAG) is a chain-like disaccharide that is linked to
      polypeptide core to connect two collagen fibrils/fibers and provide the
      intermolecular force in Collagen-GAG matrix (C-G matrix). Thus, the distribution
      of GAG in C-G matrix contributes to the integrity and mechanical properties of
      the matrix and related tissue. This paper analyzes the transverse isotropic
      distribution of GAG in C-G matrix. The angle of GAGs related to collagen fibrils
      is used as parameters to qualify the GAGs isotropic characteristic in both 3D and
      2D rendering. Statistical results included that over one third of GAGs were
      perpendicular directed to collagen fibril with symmetrical distribution for both
      3D matrix and 2D plane cross through collagen fibrils. The three factors tested
      in this paper: collagen radius, collagen distribution, and GAGs density, were not
      statistically significant for the strength of Collagen-GAG matrix in 3D
      rendering. However in 2D rendering, a significant factor found was the radius of
      collagen in matrix for the GAGs directed to orthogonal plane of Collagen-GAG
      matrix. Between two cross-section selected from Collagen-GAG matrix model, the
      plane cross through collagen fibrils was symmetrically distributed but the total
      percentage of perpendicular directed GAG was deducted by decreasing collagen
      radius. There were some symmetry features of GAGs angle distribution in selected
      2D plane that passed through space between collagen fibrils, but most models
      showed multiple peaks in GAGs angle distribution. With less GAGs directed to
      perpendicular of collagen fibril, strength in collagen cross-section weakened.
      Collagen distribution was also a factor that influences GAGs angle distribution
      in 2D rendering. True hexagonal collagen packaging is reported in this paper to
      have less strength at collagen cross-section compared to quasi-hexagonal collagen
      arrangement. In this work focus is on GAGs matrix within the collagen and its
      relevance to anisotropy. 

PMID- 25570855
TI  - Computational predictions of structures of multichromosomes of budding yeast.
AB  - Knowledge of the global architecture of the cell nucleus and the spatial
      organization of genome is critical for understanding gene expression and nuclear
      function. Single-cell imaging techniques provide a wealth of information on the
      spatial organization of chromosomes. Computational tools for modelling chromosome
      structure have broad implications in studying the effect of cell nucleus on
      higher-order genome organization. Here we describe a multichromosome constrained
      self-avoiding chromatin model for studying ensembles of genome structural models
      of budding yeast nucleus. We successfully generated a large number of model
      genomes of yeast with appropriate chromatin fiber diameter, persistence length,
      and excluded volume under spatial confinement. By incorporating details of the
      constraints from single-cell imaging studies, our method can model the budding
      yeast genome realistically. The model developed here provides a general
      computational framework for studying the overall architecture of budding yeast
      genome. 

PMID- 25570857
TI  - Context-aware semi-supervised motif detection approach.
AB  - Motif detection has raised as an important task in bioinformatics. Recently, the
      discovery of motifs that are localized relative to a certain biological area has
      become an important task in many applications. For example, it is used to
      discover regulatory sequences beside the transcription start site and the
      neighborhood of known transcription factor binding sites [1]. Therefore, the idea
      of context aware motif detection approach is needed. Moreover, there is an
      interest to use both labeled and unlabeled sets to enhance the motif detection
      approaches. In this paper, three novel context aware semi-supervised motif
      detection approaches are proposed, which are self-learning, context aware and co
      training context aware systems. In self-learning motif Hidden Markov Model (HMM)
      is enhanced independently using unlabeled sets. While in co-training, three
      different models are trained based on three different views which are pre-motif
      sequences, motif sequences and post-motif sequences. Moreover, our co-training
      context aware system is suitable for parallelization to enhance its execution
      time. The approaches were evaluated using human motif sequences and the results
      show that co-training context aware system has achieved the best results. The
      results also show that our approach outperforms other related works in [1], [2]
      and [3]. 

PMID- 25570858
TI  - Multi-level gene/MiRNA feature selection using deep belief nets and active
      learning.
AB  - Selecting the most discriminative genes/miRNAs has been raised as an important
      task in bioinformatics to enhance disease classifiers and to mitigate the
      dimensionality curse problem. Original feature selection methods choose
      genes/miRNAs based on their individual features regardless of how they perform
      together. Considering group features instead of individual ones provides a better
      view for selecting the most informative genes/miRNAs. Recently, deep learning has
      proven its ability in representing the data in multiple levels of abstraction,
      allowing for better discrimination between different classes. However, the idea
      of using deep learning for feature selection is not widely used in the
      bioinformatics field yet. In this paper, a novel multi-level feature selection
      approach named MLFS is proposed for selecting genes/miRNAs based on expression
      profiles. The approach is based on both deep and active learning. Moreover, an
      extension to use the technique for miRNAs is presented by considering the
      biological relation between miRNAs and genes. Experimental results show that the
      approach was able to outperform classical feature selection methods in
      hepatocellular carcinoma (HCC) by 9%, lung cancer by 6% and breast cancer by
      around 10% in F1-measure. Results also show the enhancement in F1-measure of our
      approach over recently related work in [1] and [2]. 

PMID- 25570859
TI  - BER performance of implant-to-air high-speed UWB data communications for neural
      recording systems.
AB  - Implant-to-air ultra-wideband communication systems are interesting for neural
      recording systems due to their low power consumption and high data-rates. In this
      paper we investigate the performance of an implant-to-air wireless link using a
      realistic model of the biological channel for neural recording systems. We
      propose an optimized fifth-derivative Gaussian pulse as a transmitted waveform
      for different modulations: binary phase shift keying (BPSK), on-off keying (OOK)
      and differential phase shift keying (DPSK). Monitoring of neural responses with
      high resolution in the brain requires a high data rate link as the number of
      electrodes is increased. Each electrode needs a data rate around 800 kb/s to
      support its neural channel. As we target more than 512 electrodes, we require a
      data link higher than 400 Mbps. 

PMID- 25570860
TI  - Capacity of UWB wireless channel for neural recording systems.
AB  - Ultra wide-band (UWB) short-range communication systems are valuable in medical
      technology, particularly for implanted devices, due to their low-power
      consumption, low cost, small size and high data rates. Monitoring of neural
      responses in the brain requires high data rate if we target a system supporting a
      large number of sensors. In this work, we are interested in the evaluation of the
      capacity of the ultra wide-band (UWB) channel that we could exploit using a
      realistic model of the biological channel. The channel characteristics are
      examined under two scenarios that are related to TX antenna placements. Using
      optimal power spectrum allocation (OPSA) at the transmitter side, we have
      computed this capacity by taking into account the fading characteristics of the
      channel. The results show the pertinence of the optimal power spectrum allocation
      for this type of channel. An improvement by a factor of 2 to 3 over a uniform
      power spectrum allocation (UPSA) when the SNR <; 0 dB was obtained. When the SNR
      is > 40 dB, both approaches give similar results. Antennas placement is examined
      under two scenarios having contrasting power constraints. 

PMID- 25570861
TI  - Multichannel wireless ECoG array ASIC devices.
AB  - Surgical resection of epileptogenic foci is often a beneficial treatment for
      patients suffering debilitating seizures arising from intractable epilepsy [1],
      [2], [3]. Electrodes placed subdurally on the surface of the brain in the form of
      an ECoG array is one of the multiple methods for localizing epileptogenic zones
      for the purpose of defining the region for surgical resection. Currently,
      transcutaneous wires from ECoG grids limit the duration of time that implanted
      grids can be used for diagnosis. A wireless ECoG recording and stimulation system
      may be a solution to extend the diagnostic period. To avoid the transcutaneous
      connections, a 64-channel wireless silicon recording/stimulating ASIC was
      developed as the electronic component of a wireless ECoG array that uses SIROF
      electrodes on a polyimide substrate[4]. Here we describe two new ASIC devices
      that have been developed and tested as part of the on-going wireless ECoG system
      design. 

PMID- 25570862
TI  - Towards addressable wireless microstimulators based on electronic rectification
      of epidermically applied currents.
AB  - Electrical stimulation has been explored to restore the capabilities of the
      nervous system in paralysis patients. This area of research and of clinical
      practice, known as Functional Electrical Stimulation, would greatly benefit from
      further miniaturization of implantable stimulators. To that end, we recently
      proposed and demonstrated an innovative electrical stimulation method in which
      implanted microstimulators operate as rectifiers of bursts of innocuous high
      frequency current supplied by skin electrodes, thus generating low frequency
      currents capable of stimulating excitable tissues. A diode could suffice in some
      applications but, in order to broaden the method's clinical applicability, we
      envision rectifiers with advanced capabilities such as current control and
      addressability. We plan flexible thread-like implants (diameters < 300 MUm)
      containing ASICs. As an intermediate stage, we are developing macroscopic
      implants (diameters ~ 2 mm) made of off-the-shelf components. Here we present a
      circuit which responds to commands modulated within the high frequency bursts and
      which is able to deliver charge-balanced currents. We show that a number of these
      circuits can perform independent stimulation of segments of an anesthetized
      earthworm following commands from a computer.

PMID- 25570863
TI  - Modular assembly concept for 3D neural probe prototypes offering high freedom of
      design and alignment precision.
AB  - The new assembly technology developed in this research provides a means to extend
      planar intracortical neural probes with one-dimensional (1D) and two-dimensional
      (2D) electrode arrangements into complex three-dimensional (3D) neural probes.
      The approach is based on novel silicon stacking modules realized using
      microsystems technologies. With these microcomponents, 3D probes can be assembled
      flexibly and tailored to the demands of neuroscientific experiments. The
      manufacturing process of the stacking modules provides the possibility to adjust
      the electrode spacing in the stacking direction with micrometer precision. The
      assembly method is demonstrated with 32-channel systems comprising 7-mm-long and
      50-MUm-thin neural probes. The angular alignment between the neural probes and
      their stacking modules after assembly as well as the vertical electrode pitch
      were determined to be about 1 degrees  and 353+/-15 MUm, respectively. 

PMID- 25570864
TI  - A polymer-metal two step sealing concept for hermetic neural implant packages.
AB  - In this paper, we introduce a technique for double-sealed ceramic packages for
      the long-term protection of implanted electronics against body fluids. A
      sequential sealing procedure consisting of a first step, during which the package
      is sealed with epoxy, protecting the implant electronics from aggressive flux
      fumes. These result from the application of the actual moisture barrier which is
      a metal seal applied in a second step by soft soldering. Epoxy sealing is carried
      out in helium atmosphere for later fine leak testing. The solder seal is applied
      on the laboratory bench. After the first sealing step, a satisfactory barrier for
      moisture is already achieved with values for helium leakage of usually LHe =
      6.10(-8) mbar 1 s(-1). After solder sealing, a very low leakage rate of LHe <=
      1.10(-12) mbar 1 s(-1) was found, which was the lower detection limit of the
      measurement setup, suggesting excellent hermeticity and hence moisture barrier.
      Presuming an implant package volume of V >= 0.5 cm(3), the time to reach a
      critical humidity of p = 5000 ppm H2O inside the package will be longer than any
      anticipated average life of human patients. 

PMID- 25570865
TI  - An integrated neuro-robotic interface for stroke rehabilitation using the NASA X1
      powered lower limb exoskeleton.
AB  - Stroke remains a leading cause of disability, limiting independent ambulation in
      survivors, and consequently affecting quality of life (QOL). Recent technological
      advances in neural interfacing with robotic rehabilitation devices are promising
      in the context of gait rehabilitation. Here, the X1, NASA's powered robotic lower
      limb exoskeleton, is introduced as a potential diagnostic, assistive, and
      therapeutic tool for stroke rehabilitation. Additionally, the feasibility of
      decoding lower limb joint kinematics and kinetics during walking with the X1 from
      scalp electroencephalographic (EEG) signals--the first step towards the
      development of a brain-machine interface (BMI) system to the X1 exoskeleton--is
      demonstrated.

PMID- 25570866
TI  - Observation-based training for neuroprosthetic control of grasping by amputees.
AB  - Current brain-machine interfaces (BMIs) allow upper limb amputees to position
      robotic arms with a high degree of accuracy, but lack the ability to control hand
      pre-shaping for grasping different objects. We have previously shown that low
      frequency (0.1-1 Hz) time domain cortical activity recorded at the scalp via
      electroencephalography (EEG) encodes information about grasp pre-shaping. To
      transfer this technology to clinical populations such as amputees, the challenge
      lies in constructing BMI models in the absence of overt training hand movements.
      Here we show that it is possible to train BMI models using observed grasping
      movements performed by a robotic hand attached to amputees' residual limb. Three
      transradial amputees controlled the grasping motion of an attached robotic hand
      via their EEG, following the action-observation training phase. Over multiple
      sessions, subjects successfully grasped the presented object (a bottle or a
      credit card) in 53+/-16 % of trials, demonstrating the validity of the BMI
      models. Importantly, the validation of the BMI model was through closed-loop
      performance, which demonstrates generalization of the model to unseen data. These
      results suggest 'mirror neuron system' properties captured by delta band EEG that
      allows neural representation for action observation to be used for action control
      in an EEG-based BMI system. 

PMID- 25570868
TI  - Brain connectivity in continuous error tasks.
AB  - Error-related potentials (ErrP) have been recently incorporated in brain-machine
      interfaces (BMIs) due to its ability to adapt and correct both the output of the
      BMI or the behavior of the machine. Most of these applications rely on
      synchronous tasks with different user's evaluations associated to correct and
      wrong events. Asynchronous detection during the continuous evaluation of the
      task, however, has to cope with background noise and an increased number of
      misdetections common in event-related potential detection. This paper studies a
      different characteristic that may carry additional information to be exploited by
      asynchronous ErrP detectors: brain connectivity coherence patterns appearing
      while the user monitors the continuous operation of a device. The results
      obtained with five subject revealed the presence of an error potential in an
      asynchronous reaching task an showed an increase in the coherency within the
      theta band. 

PMID- 25570867
TI  - Hybrid frequency and phase coding for a high-speed SSVEP-based BCI speller.
AB  - Steady-state visual evoked potential (SSVEP)-based brain-computer interfaces
      (BCIs) have potential to realize high-speed communication between the human brain
      and the external environment. Recently, multiple access (MA) methods in
      telecommunications have been introduced into the system design of BCIs and showed
      their potential in improving BCI performance. This study investigated the
      feasibility of hybrid frequency and phase coding methods in multi-target SSVEP
      based BCIs. Specifically, this study compared two hybrid target-coding
      strategies: (1) mixed frequency and phase coding, and (2) joint frequency and
      phase coding. In a simulated online BCI experiment using a 40-target BCI speller,
      BCI performance for both coding approaches were tested with a group of six
      subjects. At a spelling speed of 40 characters per minute (1.5 seconds per
      character), both approaches obtained high information transfer rates (ITR) (mixed
      coding: 172.37+/-28.67 bits/min, joint coding: 170.94+/-28.32 bits/min) across
      subjects. There was no statistically significant difference between the two
      approaches (p>0.05). These results suggest that the hybrid frequency and phase
      coding methods are highly efficient for multi-target coding in SSVEP BCIs with a
      large number of classes, providing a practical solution to implement a high-speed
      BCI speller. 

PMID- 25570869
TI  - Neural distance amplification of lexical tone in human auditory cortex.
AB  - In tonal languages, like Chinese, lexical tone serves as a key feature to provide
      contrast in word meaning. Behavior studies suggest that Mandarin Chinese tone is
      categorically perceived. However, the neural mechanism underlying Mandarin tone
      perception is still poorly understood. In this study, an Oddball paradigm was
      designed by selecting two standard-deviant stimulus pairs with same physical
      distance but different category labels, among the synthesized tones with
      continuously varying pitch contours. Using electrocorticography (ECoG) recording
      over human auditory cortex, high temporal and spatial resolution cortical neural
      signals were used for the first time to investigate the cortical processing of
      lexical tone. Here, we found different neural responses to the two standard
      deviant tone pairs, and the difference increased from low to high level along the
      hierarchy of human auditory cortex. In the two dimensional neural space, cross
      category neural distance of lexical tones is selectively amplified on those high
      level electrodes. These findings support a hierarchical and categorical model of
      Mandarin tone perception, and favor the using of high-level electrodes for a
      better performance of lexical tone discrimination in speech brain computer
      interface. 

PMID- 25570870
TI  - Visually stimulated brain-computer interfaces compete with eye tracking
      interfaces when using small targets.
AB  - Visually stimulated brain-computer interfacing detects which target on a screen a
      user is gazing at; however, this is also accomplished by tracking gaze points
      with a camera. These two approaches have been independently investigated and
      sometimes doubts about BCI with visual stimuli are raised in terms of usability
      compared to eye tracking interfaces (ETI). This paper answers this question by
      investigating information transfer rates (ITR) and recognition accuracies of BCI
      and ETI having a similar interface design, where subjects were asked to gaze at
      one of four targets on a screen. Experimental results revealed that BCI is
      comparable in ITR to ETI and had better performance for relatively small targets
      on the screen. 

PMID- 25570871
TI  - Lower-limb multi-joint stiffness of knee and ankle.
AB  - Lower-limb multi-joint (knee and ankle) stiffness may play an important role in
      functional activities such as walking, and may be significantly altered post
      stroke. Thus, determination of lower-limb multi joint stiffness matrix is
      important for better understanding of gait and of pathological changes post
      stroke. In this study, using novel dynamics decomposition, the knee and ankle
      joint stiffness matrix including cross-coupled stiffness terms between the two
      joints were determined and reported ever first. The determined stiffness matrix
      may be useful for gait studies, and can be served as a baseline for studying
      pathophysiological changes post stroke. 

PMID- 25570872
TI  - Orthopaedic applications of a validated force-based biomechanical model of the
      index finger.
AB  - An anatomically realistic biomechanical model of the index finger was created
      using a force-based approach in order to predict the isometric fingertip force or
      dynamic movement based on the forces of 7 index finger musculotendons. The model
      was validated for static forces through comparison with experimental results from
      5 cadaver specimens. The model reliably simulated the isometric fingertip force
      produced by loading individual tendons. The average error in fingertip force
      direction was less than 2 degrees  and the average error in magnitude was less
      than 10% across finger postures for each muscle. Subsequent employment of the
      model to examine force transmission from the long flexors revealed a strong
      dependence of joint contact force on finger posture for a given tendon load. This
      may have ramifications for osteoarthritis as high joint contact forces are
      thought to contribute to the disease. 

PMID- 25570873
TI  - A survey of phase variable candidates of human locomotion.
AB  - Studies show that the human nervous system is able to parameterize gait cycle
      phase using sensory feedback. In the field of bipedal robots, the concept of a
      phase variable has been successfully used to mimic this behavior by
      parameterizing the gait cycle in a time-independent manner. This approach has
      been applied to control a powered transfemoral prosthetic leg, but the proposed
      phase variable was limited to the stance period of the prosthesis only. In order
      to achieve a more robust controller, we attempt to find a new phase variable that
      fully parameterizes the gait cycle of a prosthetic leg. The angle with respect to
      a global reference frame at the hip is able to monotonically parameterize both
      the stance and swing periods of the gait cycle. This survey looks at multiple
      phase variable candidates involving the hip angle with respect to a global
      reference frame across multiple tasks including level-ground walking, running,
      and stair negotiation. In particular, we propose a novel phase variable candidate
      that monotonically parameterizes the whole gait cycle across all tasks, and does
      so particularly well across level-ground walking. In addition to furthering the
      design of robust robotic prosthetic leg controllers, this survey could help
      neuroscientists and physicians study human locomotion across tasks from a time
      independent perspective. 

PMID- 25570874
TI  - An in-vivo lateral ankle ligament strain behavior assessment technique for
      potential use in robot-assisted therapy.
AB  - Ankle sprains are very common, especially in sports activities. Accurate
      assessment of ankle ligament strain behavior is crucial in understanding ankle
      function and optimizing ankle rehabilitation programs. This study proposed an in
      vivo lateral ankle ligament strain assessment technique for potential use in
      robot-assisted therapy. It consists of two phases: real-time identification of
      ankle joint and subtalar joint orientations and simulation of lateral ankle
      ligament strain behavior. A healthy participant conducted robot-assisted
      rehabilitation exercises and the results compared to a kinematic model. The model
      was found to be realistic, leading to the conclusion that this method may be
      appropriate for determining lateral ankle ligament strain in robot-assisted
      therapy. 

PMID- 25570875
TI  - Analysis of shear wave propagation derived from MR elastography in 3D thigh
      skeletal muscle using subject specific finite element model.
AB  - The purpose of this study was to develop a subject specific finite element model
      derived from MRI images to numerically analyze the MRE (magnetic resonance
      elastography) shear wave propagation within skeletal thigh muscles. A sagittal T2
      CUBE MRI sequence was performed on the 20-cm thigh segment of a healthy male
      subject. Skin, adipose tissue, femoral bone and 11 muscles were manually
      segmented in order to have 3D smoothed solid and meshed models. These tissues
      were modeled with different constitutive laws. A transient modal dynamics
      analysis was applied to simulate the shear wave propagation within the thigh
      tissues. The effects of MRE experimental parameters (frequency, force) and the
      muscle material properties (shear modulus: C10) were analyzed through the
      simulated shear wave displacement within the vastus medialis muscle. The results
      showed a plausible range of frequencies (from 90Hz to 120 Hz), which could be
      used for MRE muscle protocol. The wave amplitude increased with the level of the
      force, revealing the importance of the boundary condition. Moreover, different
      shear displacement patterns were obtained as a function of the muscle mechanical
      properties. The present study is the first to analyze the shear wave propagation
      in skeletal muscles using a 3D subject specific finite element model. This study
      could be of great value to assist the experimenters in the set-up of MRE
      protocols. 

PMID- 25570876
TI  - A simulation study of marrow fat effect on bone biomechanics.
AB  - Bone marrow was assumed to be negligible on the aspect of bone mechanical
      behavior, where bone mass and bone mineral density were most studied. As a
      result, if the bone marrow, especially the marrow fat, plays a role in the bone
      mechanical properties is unknown yet. Marrow fat content was found increased in
      osteoporotic bone. However, the relationship between such change of bone marrow
      and bone strength is not clear yet. This study was proposed to investigate the
      effect of marrow fat on the bone biomechanical performance by computer
      simulations. A finite element model was established based on trabecular structure
      extracted from quantitative CT at L3 vertebrae. Simulations were conducted on the
      models with and without marrow fat under the same condition, respectively. The
      results showed that the cancellous bone with marrow fat had a 7.56%~18.81% higher
      maximum stress in trabeculae. Further, trabeculae with higher Young's modulus
      tend to sustain a higher maximum compressive stress when considering the marrow
      fat. As a conclusion, the marrow fat has effect on bone biomechanics, which
      cannot be ignored. Such effect in osteoporosis should be further investigated in
      deep. 

PMID- 25570877
TI  - Non-invasive method to detect the changes of glucose concentration in whole blood
      using photometric technique.
AB  - A non-invasive method is developed to monitor rapid changes in blood glucose
      levels in diabetic patients. The system depends on an optical cell built with a
      LED that emits light of wavelength 535nm, which is a peak absorbance of
      hemoglobin. As the glucose concentration in blood decreases, its osmolarity also
      decreases and the Red Blood Cells (RBCs) swell and decrease the path length
      absorption coefficient. Decreasing absorption coefficient increases the
      transmission of light through the whole blood. The system was tested with a
      constructed optical cell that held whole blood in a capillary tube. As expected
      the light transmitted to the photodiode increases with decreasing glucose
      concentration. The average response time of the system was between 30-40 seconds.

PMID- 25570878
TI  - System-level design of an RFID sweat electrolyte sensor patch.
AB  - Wearable digital health devices are dominantly found in rigid form factors such
      as bracelets and pucks. An adhesive RFID sensor bandage (patch) is reported,
      which can be made completely intimate with human skin, a distinct advantage for
      chronological monitoring of biomarkers in sweat. In this demonstration, a
      commercial RFID chip is adapted with minimum components to allow potentiometric
      sensing of mM ionic solutes in sweat, and surface temperature, as read by an
      Android smart-phone app (in-vitro tests). 

PMID- 25570879
TI  - Development and initial testing of a novel slime mould biosensor.
AB  - A plurality of whole cell biosensors have been developed using many different
      cell types. Biosensors incorporate biomolecular components or whole cells to
      facilitate specific analyte interaction; research documented here presents a
      novel whole cell biosensor based on the slime mould Physarum polycephalum (PP).
      The electrical response of PP when exposed to multiple chemicals are measured and
      quantified in terms of amplitude and frequency response. The PP biosensor is
      capable of detecting the tested chemicals and individually identifying a large
      number in terms of a specific shift in either oscillation frequency or amplitude.
      However, it does exhibit a sensitivity to environmental changes such as light
      level and temperature which may interfere with the detection of the target
      analyte but could also be used for wider sensing applications. It is proposed
      that this novel biosensor is capable of detecting many organic chemicals beyond
      those presented in this work and that the biosensor may be used for environmental
      monitoring and toxicity evaluation. 

PMID- 25570880
TI  - Evaluation of a novel tracking system in a breathing lung model.
AB  - We present the evaluation of an electromagnetic position tracking system for use
      with virtual bronchoscopy systems. Our system utilises a planar magnetic coil
      array and commercially available search coil sensors. Experimental results show
      the EM tracking accuracy to be in the range of 11.5mm, which is comparable to
      both commercial and research systems. The use of a bench-top breathing lung model
      is used to verify system operation in the in vitro setting. A novel fiducial-free
      registration method is implemented to reduce errors resulting from inaccurate
      landmark identification commonly associated with point-based registration. After
      registration, there is good agreement between the measured position of the sensor
      probe during endoscopic navigation and the lung airways as visualised in a 3D
      model of the phantom. 

PMID- 25570881
TI  - Non-invasive electrohysterogram recording using flexible concentric ring
      electrode.
AB  - Non-invasive electrohysterogram (EHG) recording could provide valuable
      information about uterine dynamics. Bipolar EHG has usually been performed using
      monopolar disposable electrodes. Recently concentric ring electrodes have been
      used for EHG recordings so as to acquire more localized electrical activity which
      may be helpful for deducing uterine contraction efficiency. Nevertheless
      concentric ring electrodes have commonly been implemented in rigid substrates.
      Therefore they do not adapt to the body surface curvature which may cause
      discomfort for patients and a poor contact between electrode and skin. The aim of
      this paper is to examine the feasibility of picking up EHG signals (BC-EHG) using
      a new flexible tripolar concentric ring (TCR) electrode placed on the abdominal
      surface, and to compare it with the conventional bipolar recordings. For this
      purpose, a total of 7 recording sessions were carried out in 7 pregnant women.
      Each recording implied simultaneous acquisition of one bipolar EHG signal and of
      two bipolar concentric EHG (BC-EHG) signals using the flexible TCR electrode.
      Then a set of temporal and spectral parameters was computed from both bipolar EHG
      and BC-EHG bursts. Experimental results show no noticeable difference in duration
      and in dominant frequency in Fast Wave High frequency range. Nonetheless, the low
      frequency content (0.1-0.2 Hz) of BC-EHG records is smaller than that of bipolar
      record. These results suggest that the new flexible TCR electrode permits to pick
      up uterine electrical activity and may provide additional information for
      deducing uterine efficiency. 

PMID- 25570882
TI  - Evolution of the complex permittivity of biological tissue at microwaves ranges:
      correlation study with burn depth.
AB  - The evolution of the muscle tissue's complex permittivity represents a growing
      interest in terms of characterization in medicine and biology. The influence of a
      burned part on the permittivity is not very developed. In this work, an
      estimation of the complex permittivity of biological tissues is performed as a
      function of the depth of burn tissues. The sensor, an open-ended coaxial probe,
      is placed directly against each sample. The evolution of the complex permittivity
      is studied for two measurements conditions (in the air and in a physiological
      solution). A correlation study is attempted with the depth of burn tissue. 

PMID- 25570883
TI  - Human balance responses to perturbations in the horizontal plane.
AB  - Human balance strategies during standing have been studied extensively. Most of
      these studies rely on perturbations to the feet, for example by moving platforms
      or treadmills, and focus on the sagittal plane. Less research has been done on
      reactions to perturbations to the upper body, and the direction dependence of
      stabilizing strategies is still an open question. Here, we describe an experiment
      where we apply horizontal static pulling forces to the upper body of standing
      human subjects in different directions by means of an overhead robotic device,
      the FLOAT. Based on a simplified mechanical model, we propose the normalized
      displacement of the center of pressure, the DeltaCoPn, as a measure of the
      selected balance strategy. We find that existing neuromechanical models do not
      fully explain responses to these static horizontal forces, because they predict
      too much CoP movement. Further, we found a tendency to particularly reduce CoP
      movement in anterior-posterior direction, indicating that reconfiguration of the
      body may play a larger role in this direction. 

PMID- 25570884
TI  - Modulation of ankle stiffness during postural sway.
AB  - Ankle stiffness is a nonlinear, time-varying system which contributes to the
      control of human upright stance. This study sought to examine the nature of the
      contribution of stiffness to postural control by determining how intrinsic and
      reflex stiffnesses varied with sway. Subjects were instructed to stand quietly on
      a bilateral electro-hydraulic actuator while perturbations were applied about the
      ankle. Subjects performed three types of trials: normal stance, forward lean, and
      backward lean. Position, torque, and EMGs from the tibialis anterior and triceps
      surae were recorded. Background torque, intrinsic stiffness and reflex stiffness
      were calculated for each perturbation. Intrinsic and reflex stiffnesses were
      heavily modulated by postural sway. Moreover, they were modulated in a
      complimentary manner; intrinsic stiffness was lowest when reflex gain was
      highest, and vice versa. These findings suggest that intrinsic stiffness is
      modulated simultaneously with reflex stiffness to optimize the control of
      balance. 

PMID- 25570885
TI  - Detecting neuropathy using measures of motor unit activation extracted from
      standard concentric needle electromyographic signals.
AB  - OBJECTIVE: Motor unit loss associated with neuropathic disorders affects motor
      unit activation. Quantitative electromyographic (EMG) features of motor unit
      activation estimated from the sequences of motor unit potentials (MUPs) created
      by concurrently active motor units can support the detection of neuropathic
      disorders. Interpretation of most motor unit activation feature values are,
      however, confounded by uncertainty regarding the level of muscle activation
      during EMG signal detection. A set of new features circumventing these
      limitations are proposed, and their utility in detecting neuropathy is
      investigated using simulated and clinical EMG signals. METHODS: The firing
      sequence of a motor neuron was simulated using a compartmentalized Hodgkin-Huxley
      based model. A pool of motor neurons was modelled such that each motor neuron was
      subjected to a common level of activation. The detection of the firing sequence
      of a motor neuron using a clinically detected EMG signal was simulated using a
      model of muscle anatomy combined with a model representing muscle fiber
      electrophysiology and the voltage detection properties of a concentric needle
      electrode. SIGNIFICANCE: Findings are based on simulated EMG data representing 30
      normal and 30 neuropathic muscles as well as clinical EMG data collected from the
      tibialis anterior muscle of 48 control subjects and 30 subjects with neuropathic
      disorders. These results demonstrate the possibility of detecting neuropathy
      using motor unit recruitment and mean firing rate feature values estimated from
      standard concentric needle detected EMG signals.

PMID- 25570886
TI  - Locomotion mode identification for lower limbs using neuromuscular and joint
      kinematic signals.
AB  - Recent development in lower limb prosthetics has seen an emergence of powered
      prosthesis that have the capability to operate in different locomotion modes.
      However, these devices cannot transition seamlessly between modes such as level
      walking, stair ascent and descent and up slope and down slope walking. They
      require some form of user input that defines the human intent. The purpose of
      this study was to develop a locomotion mode detection system and evaluate its
      performance for different sensor configurations and to study the effect of
      locomotion mode detection with and without electromyography (EMG) signals while
      using kinematic data from hip joint of non-dominant/impaired limb and an
      accelerometer. Data was collected from four able bodied subjects that completed
      two circuits that contained standing, level-walking, ramp ascent and descent and
      stair ascent and descent. By using only the kinematic data from the hip joint and
      accelerometer data the system was able to identify the transitions, stance and
      swing phases with similar performance as compared to using only EMG and
      accelerometer data. However, significant improvement in classification error was
      observed when EMG, kinematic and accelerometer data were used together to
      identify the locomotion modes. The higher recognition rates when using the
      kinematic data along with EMG shows that the joint kinematics could be beneficial
      in intent recognition systems of locomotion modes. 

PMID- 25570887
TI  - Effect of arm dominance on long-latency stabilizing reflex gain during posture.
AB  - Handedness has been proposed as a laterality of motor control specialization: the
      dominant limb specializes in controlling limb trajectory using feed-forward
      mechanisms, while the non-dominant limb is specialized for position control,
      reliant largely upon feedback mechanisms. Experimental motor control research has
      tended to use the dominant arm, which could bias our understanding of control
      toward dominant-sided mechanisms. To determine if this is the case for our work
      on rapid motor responses, we here investigate the effect of laterality on long
      latency reflexes, which are a rapid feedback response to perturbations of limb
      posture. Our results confirm previous work showing that environmental
      instabilities increase long-latency reflex gain, but we did not observe any
      difference between the dominant and non-dominant arm. Both arms displayed similar
      reflex responses during a stabilizing postural task, despite the proposed
      advantage of the non-dominant side for position feedback control. This suggests
      that the lateralized specialization of motor control is confined to different
      cortical pathways than those involved in this reflex response. 

PMID- 25570888
TI  - Modular control of movement and posture by the corticospinal alpha-gamma motor
      systems.
AB  - It is widely assumed that neural control of movement is carried out by the a
      motor system sufficiently. The role of the gamma motor system in movement and
      posture has not been adequately addressed in motor control studies. Here, we
      propose a modular control model for movement and posture based on propriospinal
      neuronal (PN) network and spinal alpha-gamma motor system. In the modular control
      model, the a and gamma motor commands are divided into static and dynamic
      functions. The static commands are specified by the higher center of brain for
      posture control, and the dynamic commands for movement generation, respectively.
      Centrally planned kinematics based on the minimal jerk criterion is conveyed to
      the periphery via the gamma motor system, while centrally programmed bi-phasic
      burst pattern of muscle activation is relayed to a pair of antagonistic muscles
      through the a motor system via the PN. Results of simulation showed that elbow
      kinematics and biceps and triceps activations displayed the similar kinematic and
      EMG features of fast reaching movement in human. This suggests a hypothesis that
      the alpha-gamma motor systems can achieve modular control of movement and posture
      in parallel. 

PMID- 25570889
TI  - An assistive controller for a lower-limb exoskeleton for rehabilitation after
      stroke, and preliminary assessment thereof.
AB  - This paper describes a novel controller, intended for use in a lower-limb
      exoskeleton, to aid gait rehabilitation in patients with hemiparesis after
      stroke. The controller makes use of gravity compensation, feedforward movement
      assistance, and reinforcement of isometric joint torques to achieve assistance
      without dictating the spatiotemporal nature of joint movement. The patient is
      allowed to self-select walking speed and is able to make trajectory adaptations
      to maintain balance without interference from the controller. The governing
      equations and the finite state machine which comprise the system are described
      herein. The control architecture was implemented in a lower-limb exoskeleton and
      a preliminary experimental assessment was conducted in which a patient with
      hemiparesis resulting from stroke walked with assistance from the exoskeleton.
      The patient exhibited improvements in fast gait speed, step length asymmetry, and
      stride length in each session, as measured before and after exoskeleton training,
      presumably as a result of using the exoskeleton. 

PMID- 25570890
TI  - The variable relationship between arm and hand use: a rationale for using finger
      magnetometry to complement wrist accelerometry when measuring daily use of the
      upper extremity.
AB  - Wrist-worn accelerometers are becoming more prevalent as a means to assess use of
      the impaired upper extremity in daily life after stroke. However, wrist
      accelerometry does not measure joint movements of the hand, which are integral to
      functional use of the upper extremity. In this study, we used a custom-built, non
      obtrusive device called the manumeter to measure both arm use (via wrist
      accelerometry) and hand use (via finger magnetometry) of a group of unimpaired
      subjects while they performed twelve motor tasks at three intensities. We also
      gave the devices to four stroke subjects and asked them to wear them for six
      hours a day for one month. From the in-lab testing we found that arm use was a
      strong predictor of hand use for individual tasks, but that the slope of the
      relationship varied by up to a factor of ~12 depending on the task being
      performed. Consistent with this, in the daily use data collected from stroke
      subjects we found a broad spread in the relationship between arm and hand use.
      These results suggest that analyzing the spread of the relationship between daily
      hand and arm use will give more insight into upper extremity recovery than wrist
      accelerometry or finger magnetometry alone, because the spread reflects the
      nature of the daily tasks performed as well as the amount of upper extremity use.

PMID- 25570891
TI  - Development of a clinician worn device for the evaluation of abnormal muscle
      tone.
AB  - Neurological disorders such as cerebral palsy commonly result in abnormal muscle
      hyperactivity that negatively effects functional use of the affected limbs.
      Individuals with cerebral palsy often present with a mix of spasticity and
      dystonia, and it can be difficult to distinguish between the effects of these
      types of abnormal tone. Different types of abnormal tone respond differently to
      treatments such as deep brain stimulation and baclofen. Conventional clinical
      evaluation techniques provide minimal information for distinguishing abnormal
      tone characteristics and changes from treatment. Devices that quantify abnormal
      tone characteristics can help distinguish between the effects of different types
      of abnormal muscle tone, and help to quantify treatment effects. This paper
      discusses the development and initial evaluation of MyoSense(TM), a clinician
      worn device for the quantification and differentiation of abnormal muscle tone.
      MyoSense evaluates the orientation, speed, and force during clinician
      manipulation of the affected limbs with a protocol that is similar to
      conventional practice for evaluating abnormal tone. Evaluation of the MyoSense
      device, using a mechanical apparatus to simulate abnormal muscle tone, showed
      good resolution of abnormal tone characteristics. Using a procedure directly
      modeled after conventional clinical evaluation of abnormal tone, MyoSense data
      showed good correlation with simulated profiles, 0.8 for spasticity and 0.93 for
      hypertonia. Evaluation of average change across different limb manipulation
      speeds, to mitigate acceleration and mechanical effects, resulted in MyoSense
      data correlations to simulated profiles of 0.99 for spasticity, spasticity with a
      catch, and dystonia. Overall these results show promise for future clinical
      evaluation of the MyoSense device. 

PMID- 25570892
TI  - An open and configurable embedded system for EMG pattern recognition
      implementation for artificial arms.
AB  - Pattern recognition (PR) based on electromyographic (EMG) signals has been
      developed for multifunctional artificial arms for decades. However, assessment of
      EMG PR control for daily prosthesis use is still limited. One of the major
      barriers is the lack of a portable and configurable embedded system to implement
      the EMG PR control. This paper aimed to design an open and configurable embedded
      system for EMG PR implementation so that researchers can easily modify and
      optimize the control algorithms upon our designed platform and test the EMG PR
      control outside of the lab environments. The open platform was built on an open
      source embedded Linux Operating System running a high-performance Gumstix board.
      Both the hardware and software system framework were openly designed. The system
      was highly flexible in terms of number of inputs/outputs and calibration
      interfaces used. Such flexibility enabled easy integration of our embedded system
      with different types of commercialized or prototypic artificial arms. Thus far,
      our system was portable for take-home use. Additionally, compared with previously
      reported embedded systems for EMG PR implementation, our system demonstrated
      improved processing efficiency and high system precision. Our long-term goals are
      (1) to develop a wearable and practical EMG PR-based control for multifunctional
      artificial arms, and (2) to quantify the benefits of EMG PR-based control over
      conventional myoelectric prosthesis control in a home setting. 

PMID- 25570893
TI  - Daily-life monitoring of stroke survivors motor performance: the INTERACTION
      sensing system.
AB  - The objective of the INTERACTION Eu project is to develop and validate an
      unobtrusive and modular system for monitoring daily life activities, physical
      interactions with the environment and for training upper and lower extremity
      motor function in stroke subjects. This paper describes the development and
      preliminary testing of the project sensing platform made of sensing shirt,
      trousers, gloves and shoes. Modular prototypes were designed and built
      considering the minimal set of inertial, force and textile sensors that may
      enable an efficient monitoring of stroke patients. The single sensing elements
      are described and the results of their preliminary lab-level testing are
      reported. 

PMID- 25570894
TI  - Cooperation of electrically stimulated muscle and pneumatic muscle to realize
      RUPERT bi-directional motion for grasping.
AB  - Robot-assisted rehabilitation is an active area of research to meet the demand of
      repetitive therapy in stroke rehabilitation. Robotic upper-extremity repetitive
      trainer (RUPERT) with its unidirectional pneumatic muscle actuation (PMA) can be
      used by most stroke patients that have difficulty moving in one direction because
      of a weak agonist or hyperactive antagonist. In this research, to broaden the
      usage of RUPERT, we not only add grasping functionality to the rehabilitation
      robot with the help of surface Functional Electrical Stimulation (FES) but also
      realize the robot joint bi-directional motion by using a PMA in cooperation with
      surface FES evoked paralyzed muscle force. This integrative rehabilitation
      strategy is explored for training patients to practice coordinated reaching and
      grasping functions. The effectiveness of this FES electrically evoked bio
      actuator way is verified through a method that separates the mixed electromyogram
      (MEMG) into the electrically evoked electromyogram (EEMG) and voluntary
      electromyogram (VEMG). This is a promising approach to alleviate the size and
      mechanical complexity of the robot, thereby the cost of the joint bi-directional
      actuator rehabilitation robot by means of their own characteristics of stroke
      subjects. 

PMID- 25570895
TI  - Spatial patterns of high-frequency oscillations in the rat cerebellar cortex.
AB  - Rhythmic signals in the brain have always intrigued neuroscientists and the
      cerebellum is not an exception. Cerebellar high-frequency oscillations have been
      explored over many decades, but underlying mechanisms have remained unclear. In
      this study, we have recorded spontaneous and evoked potentials from the
      cerebellar surface with chronically implanted, multi-electrode arrays. Evoked and
      spontaneous signals during behavior showed highly synchronized oscillations at
      ~150 Hz. Furthermore, this rhythmic activity displayed directional preference on
      the cerebellar surface. This preliminary study demonstrates the presence of
      highly synchronized cerebellar oscillations in high-frequency band that emerge
      episodically in anesthetized animals by sensory stimulation as well as during
      face cleaning in awake animals. 

PMID- 25570896
TI  - An enhancement to velocity selective discrimination of neural recordings:
      extraction of neuronal firing rates.
AB  - This paper describes improvements to the theory of velocity selective recording
      (VSR) of neural signals. Action potentials are classified and differentiated
      based on their conduction velocities which can be calculated from concurrent
      neural recordings taking at different locations on a nerve. Existing work has
      focussed primarily on electrically evoked compound action potentials (CAPs) where
      only a single evoked response per velocity is recorded. This paper extends the
      theory of VSR to naturally occurring neural signals recorded from rat and
      attempts to identify the level of activity (firing rates) within particular
      velocity ranges. 

PMID- 25570897
TI  - Improving single-trial detection of event-related potentials through artificial
      deformed signals.
AB  - To propose a reliable and robust Brain-Computer Interface (BCI), efficient
      machine learning and signal processing methods have to be used. However, it is
      often necessary to have a sufficient number of labeled brain responses to create
      a model. A large database that would represent all of the possible variabilities
      of the signal is not always possible to obtain, because calibration sessions have
      to be short. In the case of BCIs based on the detection of event-related
      potentials (ERPs), we propose to tackle this problem by including additional
      deformed patterns in the training database to increase the number of labeled
      brain responses. The creation of the additional deformed patterns is based on two
      approaches: (i) smooth deformation fields, and (ii) right and left shifted
      signals. The evaluation is performed with data from 10 healthy subjects
      participating in a P300 speller experiment. The results show that small shifts of
      the signal allow a better estimation of both spatial filters, and a linear
      classifier. The best performance, AUC=0.828 +/- 0.061, is obtained by combining
      the smooth deformation fields and the shifts, after spatial filtering, compared
      to AUC=0.543 +/- 0.025, without additional deformed patterns. The results support
      the conclusion that adding signals with small deformations can significantly
      improve the performance of single-trial detection when the amount of training
      data is limited. 

PMID- 25570898
TI  - Prediction of freezing of gait using analysis of brain effective connectivity.
AB  - Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD), in
      which patients experience sudden difficulties in starting or continuing
      locomotion. It is described by patients as the sensation that their feet are
      suddenly glued to the ground. This, disturbs their balance, and hence often leads
      to falls. In this study, directed transfer function (DTF) and partial directed
      coherence (PDC) were used to calculate the effective connectivity of neural
      networks, as the input features for systems that can detect FOG based on a
      Multilayer Perceptron Neural Network, as well as means for assessing the causal
      relationships in neurophysiological neural networks during FOG episodes. The
      sensitivity, specificity and accuracy obtained in subject dependent analysis were
      82%, 77%, and 78%, respectively. This is a significant improvement compared to
      previously used methods for detecting FOG, bringing this detection system one
      step closer to a final version that can be used by the patients to improve their
      symptoms. 

PMID- 25570899
TI  - Tactile afferents encode grip safety before slip for different frictions.
AB  - Adjustments to frictional forces are crucial to maintain a safe grip during
      precision object handling in both humans and robotic manipulators. The aim of
      this work was to investigate whether a population of human tactile afferents can
      provide information about the current tangential/normal force ratio expressed as
      the percentage of the critical load capacity - the tangential/normal force ratio
      at which the object would slip. A smooth stimulation surface was tested on the
      fingertip under three frictional conditions, with a 4 N normal force and a
      tangential force generated by motion in the ulnar or distal direction at a fixed
      speed. During stimulation, the responses of 29 afferents (12 SA-I, 2 SA-II, 12 FA
      I, 3 FA-II) were recorded. A multiple regression model was trained and tested
      using cross-validation to estimate the percentage of the critical load capacity
      in real-time as the tangential force increased. The features for the model were
      the number of spikes from each afferent in windows of fixed length (50, 100 or
      200 ms) around points spanning the range from 50% to 100% of the critical load
      capacity, in 5% increments. The mean regression estimate error was less than 1%
      of the critical load capacity with a standard deviation between 5% and 10%. A
      larger number of afferents is expected to improve the estimate error. This work
      is important for understanding human dexterous manipulation and inspiring
      improvements in robotic grippers and prostheses. 

PMID- 25570901
TI  - NFC based provisioning of instructional videos to assist with instrumental
      activities of daily living.
AB  - Existing assistive living and prompting based solutions have adopted a relatively
      complex approach to supporting individuals. These solutions have involved sensor
      based monitoring, activity recognition and assistance provisioning. Traditionally
      they have suffered from a number of issues rooted in scalability and performance
      levels associated with the activity recognition process. This paper introduces a
      simplistic approach to assistive living within a user's residence through the use
      of NFC tags and smart devices. The core concept of this approach is presented and
      is subsequently placed within the context of related work. A description of the
      architecture is provided and results following technical evaluation of the first
      system prototype are discussed. 

PMID- 25570900
TI  - Detecting movement intent from scalp EEG in a novel upper limb robotic
      rehabilitation system for stroke.
AB  - Stroke can be a source of significant upper extremity dysfunction and affect the
      quality of life (QoL) in survivors. In this context, novel rehabilitation
      approaches employing robotic rehabilitation devices combined with brain-machine
      interfaces can greatly help in expediting functional recovery in these
      individuals by actively engaging the user during therapy. However, optimal
      training conditions and parameters for these novel therapeutic systems are still
      unknown. Here, we present preliminary findings demonstrating successful movement
      intent detection from scalp electroencephalography (EEG) during robotic
      rehabilitation using the MAHI Exo-II in an individual with hemiparesis following
      stroke. These findings have strong clinical implications for the development of
      closed-loop brain-machine interfaces to robotic rehabilitation systems. 

PMID- 25570902
TI  - Home-based Senior Fitness Test measurement system using collaborative inertial
      and depth sensors.
AB  - This paper presents a home-based Senior Fitness Test (SFT) measurement system by
      using an inertial sensor and a depth camera in a collaborative way. The depth
      camera is used to monitor the correct pose of a subject for a fitness test and
      any deviation from the correct pose while the inertial sensor is used to measure
      the number of a fitness test action performed by the subject within the time
      duration specified by the fitness protocol. The results indicate that this
      collaborative approach leads to high success rates in providing the SFT
      measurements under realistic conditions. 

PMID- 25570903
TI  - An investigation into the usability of the STAR training and re-skilling website
      for carers of persons with dementia.
AB  - Due to the successes in medical science people are now beginning to live much
      longer. With this brings increased problems associated with ageing, with one
      exemplar being dementia. Persons with dementia require care with activities of
      daily living, for example, with washing, dressing and eating. This requires
      additional care, which is usually provided by family and friends who assume the
      role of informal carers. Provision of care by informal carers brings irreversible
      changes to their lives that can lead to depression and feelings of loneliness. In
      part, these changes are linked with carers having insufficient understanding and
      training with dementia. The EU funded STAR project created an web portal that
      aims to provide the necessary online training that carers need, however, the
      usability of such a provision warrants investigation. This paper presents the
      findings of a usability test conducted on five carers of people with dementia
      while using the STAR Training Website. For the 21 usability issues identified,
      the paper outlines proposed solutions. 

PMID- 25570904
TI  - The creation of simulated activity datasets using a graphical intelligent
      environment simulation tool.
AB  - The availability of datasets capturing the performance of activities of daily
      living is limited by difficulties associated with the collection of such data.
      Software solutions can mitigate these limitations, providing researchers with the
      ability to rapidly generate simulated data. This paper describes the use of IE
      Sim to create a simulated intelligent environment within which activities of
      daily living can be performed using a virtual avatar. IE Sim has been
      demonstrated to facilitate the generation of datasets capturing normal activity
      performance in addition to overlapping activities and abnormal activities such as
      hazardous scenarios. 

PMID- 25570905
TI  - An open platform to support home healthcare services using interactive TV.
AB  - This paper presents an open platform to support the development and deployment of
      healthcare services at home using the TV as the main gateway. Unlike previous
      systems based on proprietary and closed solutions, our proposal is completely
      open allowing the easy integration of new services or the integration with
      external platforms. This is possible thanks to the use of a PC-based Set Top Box
      called Home Theater Personal (HTPC) that can be easily connected to the TV and
      Internet. This solution is not tight to particular Software and Hardware
      providers. It allows an easy integration of different telemedicine devices
      through Bluetooth and USB standard protocols. Additionally, any software
      developer/provider can include new services and healthcare modules through a
      simple to use add/on platform. 

PMID- 25570906
TI  - Context predictor based sparse sensing technique and smart transmission
      architecture for IoT enabled remote health monitoring applications.
AB  - In hyperconnectivity scenario, managing the amount of data acquired from sensors
      in the Body Area Networks (BANs) is one of the major issues. In this paper we
      propose an on-chip context predictor based sparse sensing technology with smart
      transmission architecture which makes use of confidence interval calculation from
      the features that present in the data, thereby achieving statistical guarantee.
      The proposed architecture uses intelligent sparse sensing, which eradicates the
      collection of redundant data, thereby reducing the amount of data generated. For
      the performance analysis, we considered ECG data acquisition and transmission
      system. The proposed architecture when applied on the data collected from 10
      patients reduces the duty cycle of the sensing unit to 27.99%, by achieving an
      energy saving of 72% and the mean deviation of sampled data from the original
      data is 2%. 

PMID- 25570907
TI  - A transdisciplinary approach to wearables, big data and quality of life.
AB  - Today, the term "wearable" goes beyond the traditional definition of clothing; it
      refers to an accessory that enables personalized mobile information processing.
      We define the concept of wearables, present their attributes and discuss their
      role at the core of an ecosystem for harnessing big data. We discuss the concept
      of a meta-wearable and propose a transdisciplinary approach to transform the
      field and enhance the quality of life for everyone. 

PMID- 25570908
TI  - The social comfort of wearable technology and gestural interaction.
AB  - The "wearability" of wearable technology addresses the factors that affect the
      degree of comfort the wearer experiences while wearing a device, including
      physical, psychological, and social aspects. While the physical and psychological
      aspects of wearing technology have been investigated since early in the
      development of the field of wearable computing, the social aspects of wearability
      have been less fully-explored. As wearable technology becomes increasingly common
      on the commercial market, social wearability is becoming an ever-more-important
      variable contributing to the success or failure of new products. Here we present
      an analysis of social aspects of wearability within the context of the greater
      understanding of wearability in wearable technology, and focus on selected
      theoretical frameworks for understanding how wearable products are perceived and
      evaluated in a social context. Qualitative results from a study of social
      acceptability of on-body interactions are presented as a case study of social
      wearability. 

PMID- 25570909
TI  - Posture and activity recognition and energy expenditure prediction in a wearable
      platform.
AB  - The use of wearable sensors coupled with the processing power of mobile phones
      may be an attractive way to provide real-time feedback about physical activity
      and energy expenditure (EE). Here we describe use of a shoe-based wearable sensor
      system (SmartShoe) with a mobile phone for real-time prediction and display of
      time spent in various postures/physical activities and the resulting EE. To deal
      with processing power and memory limitations of the phone, we introduce new
      algorithms that require substantially less computational power. The algorithms
      were validated using data from 15 subjects who performed up to 15 different
      activities of daily living during a four-hour stay in a room calorimeter. Use of
      Multinomial Logistic Discrimination (MLD) for posture and activity classification
      resulted in an accuracy comparable to that of Support Vector Machines (SVM) (90%
      vs. 95%-98%) while reducing the running time by a factor of 190 and reducing the
      memory requirement by a factor of 104. Per minute EE estimation using activity
      specific models resulted in an accurate EE prediction (RMSE of 0.53 METs vs. RMSE
      of 0.69 METs using previously reported SVM-branched models). These results
      demonstrate successful implementation of real-time physical activity monitoring
      and EE prediction system on a wearable platform. 

PMID- 25570910
TI  - Automatic identification of solid-phase medication intake using wireless wearable
      accelerometers.
AB  - We have proposed a novel solution to a fundamental problem encountered in
      implementing non-ingestion based medical adherence monitoring systems, namely,
      how to reliably identify pill medication intake. We show how wireless wearable
      devices with tri-axial accelerometer can be used to detect and classify hand
      gestures of users during solid-phase medication intake. Two devices were worn on
      the wrists of each user. Users were asked to perform two activities in the way
      that is natural and most comfortable to them: (1) taking empty gelatin capsules
      with water, and (2) drinking water and wiping mouth. 25 users participated in
      this study. The signals obtained from the devices were filtered and the patterns
      were identified using dynamic time warping algorithm. Using hand gesture signals,
      we achieved 84.17 percent true positive rate and 13.33 percent false alarm rate,
      thus demonstrating that the hand gestures could be used to effectively identify
      pill taking activity. 

PMID- 25570911
TI  - Comparative study of T-amplitude features for fitness monitoring using the
      ePatch(r) ECG recorder.
AB  - This study investigates ECG features, focusing on T-wave amplitude, from a
      wearable ECG device as a potential method for fitness monitoring in exercise
      rehabilitation. An automatic T-peak detection algorithm is presented that uses
      local baseline detection to overcome baseline drift without the need for
      preprocessing, and offers adequate performance on data recorded in noisy
      environments. The algorithm is applied to 24 hour data recordings from two
      subject groups with different physical activity histories. Results indicate that,
      while mean heart rate (HR) differs most significantly between the groups, T
      amplitude features could be useful depending on the disparities in fitness level,
      and require further investigation on an individual basis. 

PMID- 25570912
TI  - High performance flexible electronics for biomedical devices.
AB  - Plastic electronics is soft, deformable and lightweight and it is suitable for
      the realization of devices which can form an intimate interface with the body, be
      implanted or integrated into textile for wearable and biomedical applications.
      Here, we present flexible electronics based on amorphous oxide semiconductors (a
      IGZO) whose performance can achieve MHz frequency even when bent around hair. We
      developed an assembly technique to integrate complex electronic functionalities
      into textile while preserving the softness of the garment. All this and further
      developments can open up new opportunities in health monitoring, biotechnology
      and telemedicine. 

PMID- 25570913
TI  - A functional test for the detection of infusion lines extravasation.
AB  - Extravasation during intravenous (IV) infusion is a common secondary effect with
      potentially serious clinical consequences. The correct positioning of the needle
      in the vein may be difficult to confirm when no blood return is observed. In this
      paper, a novel method is proposed for the detection of extravasation during
      infusion therapy. A small volume of a sodium bicarbonate solution is
      administrated IV and, following its consecutive dissociation, an excess of carbon
      dioxide (CO2) is rapidly exhaled by the lungs. The analysis of the exhaled CO2
      signal by a pattern recognition algorithm enables the robust detection of the CO2
      excess release, thereby confirming the absence of extravasation. Initial results
      are presented for the application of the method on a group of 89 oncology
      patients. 

PMID- 25570914
TI  - Feature extraction with stacked autoencoders for epileptic seizure detection.
AB  - Scalp electroencephalogram (EEG), a recording of the brain's electrical activity,
      has been used to diagnose and detect epileptic seizures for a long time. However,
      most researchers have implemented seizure detectors by manually hand-engineering
      features from observed EEG data, and used them in seizure detection, which might
      not scale well to new patterns of seizures. In this paper, we investigate the
      possibility of utilising unsupervised feature learning, the recent development of
      deep learning, to automatically learn features from raw, unlabelled EEG data that
      are representative enough to be used in seizure detection. We develop patient
      specific seizure detectors by using stacked autoencoders and logistic
      classifiers. A two-step training consisting of the greedy layer-wise and the
      global fine-tuning was used to train our detectors. The evaluation was performed
      by using labelled dataset from the CHB-MIT database, and the results showed that
      all of the test seizures were detected with a mean latency of 3.36 seconds, and a
      low false detection rate. 

PMID- 25570915
TI  - A balanced sleep/wakefulness classification method based on actigraphic data in
      adolescents.
AB  - Several research groups have developed automated sleep-wakefulness classifiers
      for night wrist actigraphic (ACT) data. These classifiers tend to be unbalanced,
      with a tendency to overestimate the detection of sleep, at the expense of poorer
      detection of wakefulness. The reason for this is that the measure of success in
      previous works was the maximization of the overall accuracy, disregarding the
      balance between sensitivity and specificity. The databases were usually sleep
      recordings, hence the over-representation of sleep samples. In this work an
      Artificial Neural Network (ANN), sleep-wakefulness classifier is presented. ACT
      data was collected every minute. An 11-min moving window was used as observing
      frame for data analysis, as applied in previous sleep ACT studies. However, our
      feature set adds new variables such as the time of the day, the median and the
      median absolute deviation. Sleep and Wakefulness data were balanced to improve
      the system training. A comparison with previous studies can still be done, by
      choosing the point in the ROC curve associated with the corresponding data
      balance. Our results are compared with a polysomnogram-based hypnogram as golden
      standard, rendering an accuracy of 92.8%, a sensitivity of 97.6% and a
      specificity of 73.4%. Geometric mean between sensitivity and specificity is
      84.9%. 

PMID- 25570916
TI  - Swarm-wavelet based extreme learning machine for finger movement classification
      on transradial amputees.
AB  - The use of a small number of surface electromyography (EMG) channels on the
      transradial amputee in a myoelectric controller is a big challenge. This paper
      proposes a pattern recognition system using an extreme learning machine (ELM)
      optimized by particle swarm optimization (PSO). PSO is mutated by wavelet
      function to avoid trapped in a local minima. The proposed system is used to
      classify eleven imagined finger motions on five amputees by using only two EMG
      channels. The optimal performance of wavelet-PSO was compared to a grid-search
      method and standard PSO. The experimental results show that the proposed system
      is the most accurate classifier among other tested classifiers. It could classify
      11 finger motions with the average accuracy of about 94 % across five amputees. 

PMID- 25570917
TI  - Hand gesture recognition based on surface electromyography.
AB  - Human hands are the most dexterous of human limbs and hand gestures play an
      important role in non-verbal communication. Underlying electromyograms associated
      with hand gestures provide a wealth of information based on which varying hand
      gestures can be recognized. This paper develops an inter-individual hand gesture
      recognition model based on Hidden Markov models that receives surface
      electromyography (sEMG) signals as inputs and predicts a corresponding hand
      gesture. The developed recognition model is tested with a dataset of 10 various
      hand gestures performed by 25 subjects in a leave-one-subject-out cross
      validation and an inter-individual recognition rate of 79% was achieved. The
      promising recognition rate demonstrates the efficacy of the proposed approach for
      discriminating between gesture-specific sEMG signals and could inform the design
      of sEMG-controlled prostheses and assistive devices. 

PMID- 25570918
TI  - Pattern learning with deep neural networks in EMG-based speech recognition.
AB  - We report on classification of phones and phonetic features from facial
      electromyographic (EMG) data, within the context of our EMG-based Silent Speech
      interface. In this paper we show that a Deep Neural Network can be used to
      perform this classification task, yielding a significant improvement over
      conventional Gaussian Mixture models. Our central contribution is the
      visualization of patterns which are learned by the neural network. With
      increasing network depth, these patterns represent more and more intricate
      electromyographic activity. 

PMID- 25570919
TI  - Real-time prediction of respiratory motion traces for radiotherapy with ensemble
      learning.
AB  - In this paper, we introduce a hybrid method for prediction of respiratory motion
      to overcome the inherent delay in robotic radiosurgery while treating lung
      tumors. The hybrid method adopts least squares support vector machine (LS-SVM)
      based ensemble learning approach to exploit the relative advantages of the
      individual methods local circular motion (LCM) with extended Kalman filter (EKF)
      and autoregressive moving average (ARMA) model with fading memory Kalman filter
      (FMKF). The efficiency the proposed hybrid approach was assessed with the real
      respiratory motion traces of 31 patients while treating with CyberKnife(TM).
      Results show that the proposed hybrid method improves the prediction accuracy by
      approximately 10% for prediction horizons of 460 ms compared to the existing
      methods. 

PMID- 25570921
TI  - ECG-EMG separation by using enhanced non-negative matrix factorization.
AB  - We present a novel approach to single-channel ECG-EMG signal separation by means
      of enhanced non-negative matrix factorization (NMF). The approach is based on a
      linear decomposition of the input signal spectrogram in two non-negative
      components, which represent the ECG and EMG spectrogram estimates. As ECG and EMG
      have different time-frequency (TF) patterns, the decomposition is enhanced by
      reshaping the input mixture spectrogram in order to emphasize a sparse ECG over a
      noisy-like EMG. Moreover, initialization of the classical NMF algorithm with
      accurately designed ECG and EMG structures further increases its separation
      performance. The comparative study suggests that the proposed method outperforms
      two reference methods for both synthetic and real signal mixture scenarios. 

PMID- 25570920
TI  - Differences in the cerebral hemodynamics regulation mechanisms of premature
      infants with intra-ventricular hemorrhage assessed by means of phase rectified
      signal averaging.
AB  - Cerebral hemodynamics regulation consists of several mechanisms that try to keep
      brain homeostasis. In premature infants, due to the immaturity of their cerebral
      vascular bed, these mechanisms might be impaired exposing their brain to damage.
      The status of the cerebral regulation mechanism is classically assessed by
      measuring the coupling between some systemic variables, such as Mean arterial
      blood pressure (MABP) and concentration of blood gases, with surrogate
      measurements for cerebral blood flow, such as brain tissue oxygenation (rScO2)
      measured by means of Near-infrared Spectroscopy. We hypothesized that the coupled
      dynamics between systemic variables and rScO2 is different in premature infants
      that suffered from brain damage than in those with a favorable clinical outcome.
      Therefore, we explore the use of phase rectified signal averaging (PRSA) and bi
      variate PRSA (BPRSA) in order to identify these differences. We found that the
      coupled dynamics between changes in MABP and cerebral oxygenation was different
      in premature infants that suffered III-IV grade intra-ventricular haemorrhage
      (IVH), when compared to control subjects. 

PMID- 25570922
TI  - A novel outlier detection method for identifying torque-related transient
      patterns of in vivo muscle behavior.
AB  - This paper proposed a novel outlier detection method, named l1-regularized
      outlier isolation and regression (LOIRE), to examine torque-related transient
      patterns of in vivo muscle behavior from multimodal signals, including
      electromyography (EMG), mechanomyography (MMG) and ultrasonography (US), during
      isometric muscle contraction. Eight subjects performed isometric ramp contraction
      of knee up to 90% of the maximal voluntary contraction, and EMG, MMG and US were
      simultaneously recorded from the rectus femoris muscle. Five features, including
      two root mean square amplitudes from EMG and MMG, muscle cross sectional area,
      muscle thickness and width from US were extracted. Then, local polynomial
      regression was used to obtain the signal-to-torque relationships and their
      derivatives. By assuming the signal-to-torque functions are basically quadratic,
      the LOIRE method is applied to identify transient torque-related patterns of EMG,
      MMG and US features as outliers of the linear derivative-to-torque functions. The
      results show that the LOIRE method can effectively reveal transient patterns in
      the signal-to-torque relationships (for example, sudden changes around 20% MVC
      can be observed from all features), providing important information about in vivo
      muscle behavior. 

PMID- 25570923
TI  - Characterization of ultradian and circadian rhythms of core body temperature
      based on wavelet analysis.
AB  - This study was motivated by the needs of precise characterization for the
      ultradian and circadian rhythmicity of human core body temperature (CBT). The CBT
      data, two-whole-days' data of two female bed-ridden old aged suffering from
      cerebral infarction sequelae, was detrended to eliminate the long-term components
      with periods longer than two days and normalized at first. It was then analyzed
      by the stationary wavelets transform (SWT) to get the time-frequency information.
      In the step of SWT, symlet 6 was used, and the approximation waveforms in the
      5th, 6th and 7th levels were used to reveal the targeted rhythmicity. The results
      of the SWT show that SWT can faithfully reveal the time-frequency information of
      feature elements (peaks and troughs) of waveforms and rhythmicity can be
      characterized by analyzing temporal information of feature elements. 

PMID- 25570924
TI  - Detection of Obstructive sleep apnea in awake subjects by exploiting body posture
      effects on the speech signal.
AB  - Obstructive sleep apnea (OSA) is a common sleep disorder. OSA is associated with
      several anatomical and functional abnormalities of the upper airway. It was shown
      that these abnormalities in the upper airway are also likely to be the reason for
      increased rate of apneic events in the supine position. Functional and structural
      changes in the vocal tract can affect the acoustic properties of speech. We
      hypothesize that acoustic properties of speech that are affected by body position
      may aid in distinguishing between OSA and non-OSA patients. We aimed to explore
      the possibility to differentiate OSA and non-OSA patients by analyzing the
      acoustic properties of their speech signal in upright sitting and supine
      positions. 35 awake patients were recorded while pronouncing sustained vowels in
      the upright sitting and supine positions. Using linear discriminant analysis
      (LDA) classifier, accuracy of 84.6%, sensitivity of 92.7%, and specificity of
      80.0% were achieved. This study provides the proof of concept that it is possible
      to screen for OSA by analyzing and comparing speech properties acquired in
      upright sitting vs. supine positions. An acoustic-based screening system during
      wakefulness may address the growing needs for a reliable OSA screening tool;
      further studies are needed to support these findings. 

PMID- 25570925
TI  - Breathing sounds spectral and higher order statistics changes from wakefulness to
      sleep in apneic and non-apneic people.
AB  - Breathing sounds analysis conveys valuable information in relation to obstructive
      sleep apnea (OSA) during both sleep and wakefulness. In this study, we
      investigated whether the breathings sounds spectral and higher order statistics
      characteristics (HOS) change from wakefulness to sleep, and more importantly
      whether this change is associated with severity of OSA. Tracheal breathing sounds
      of 6 individuals with severe OSA and 6 non-OSA individuals during wakefulness and
      stage 2 of sleep, both in supine position, were used in this study. The sounds
      were recorded simultaneously with full overnight polysomnography (PSG)
      assessment. First, the sounds of 5 noise-free breathing cycles were extracted and
      sequestered into inspiratory and expiratory phase segments manually for each
      study subject. After normalizing each sound segment to its energy, spectral and
      HOS features were calculated. Several features including the median bispectral
      frequency (MBF), spectral bandwidth (BW) and bispectrum Harmonic Mean (HM) were
      found to change statistically significantly from wakefulness to sleep mostly in
      severe OSA group but not as much in non-OSA group. The most prominent and
      consistent change between the two groups of OSA and non-OSA was observed in MBF;
      it changed from wakefulness to sleep in the two groups in an opposite manner;
      this observation is congruent with the hypothesis that the upper airway in OSA
      population has an increased non-homogeneity. 

PMID- 25570926
TI  - Identification of Obstructive Sleep Apnea patients from tracheal breath sound
      analysis during wakefulness in polysomnographic studies.
AB  - Obstructive Sleep Apnea (OSA) is currently diagnosed by a full nocturnal
      polysomnography (PSG), a very expensive and time-consuming method. In previous
      studies we were able to distinguish patients with OSA through formant frequencies
      of breath sound during sleep. In this study we aimed at identifying OSA patients
      from breath sound analysis during wakefulness. The respiratory sound was acquired
      by a tracheal microphone simultaneously to PSG recordings. We selected several
      cycles of consecutive inspiration and exhalation episodes in 10 mild-moderate
      (AHI<;30) and 13 severe (AHI>=30) OSA patients during their wake state before
      getting asleep. Each episode's formant frequencies were estimated by linear
      predictive coding. We studied several formant features, as well as their
      variability, in consecutive inspiration and exhalation episodes. In most subjects
      formant frequencies were similar during inspiration and exhalation. Formant
      features in some specific frequency band were significantly different in mild OSA
      as compared to severe OSA patients, and showed a decreasing correlation with OSA
      severity. These formant characteristics, in combination with some anthropometric
      measures, allowed the classification of OSA subjects between mild-moderate and
      severe groups with sensitivity (specificity) up to 88.9% (84.6%) and accuracy up
      to 86.4%. In conclusion, the information provided by formant frequencies of
      tracheal breath sound recorded during wakefulness may allow identifying subjects
      with severe OSA. 

PMID- 25570927
TI  - A novel expert classifier approach to pre-screening obstructive sleep apnea
      during wakefulness.
AB  - Obstructive sleep apnea (OSA) is a widespread disorder that is cumbersome to
      diagnose using the goldstandard, overnight polysomnography (PSG). This paper
      highlights further development of our Awake-OSA method for predicting whether
      someone has severe sleep apnea using breath sounds recorded during wakefulness.
      We propose the use of an expert classification approach that consists of
      individual majority-voting classifiers. Each classifier is trained to distinguish
      one class of subject from all other classes. The outcomes of these classifiers
      are, in turn, combined using a truth matrix to determine the final outcome. Using
      the breath sound features of 249 subjects, the classifiers attempted to classify
      180 subjects as either non-OSA (AHI less than 5) or severe-OSA (AHI greater than
      30). 79% and 75% of OSA and non-OSA subjects, respectively, could be classified.
      Of those classified, the resultant testing sensitivity and specificity were found
      to be 78% and 86%, respectively. The consistency of the testing to training
      accuracies indicates the robustness and generalizability of using multiple expert
      classifiers on the dataset. This technique has the potential to be used in a
      doctor's office to rapidly and cheaply pre-screen for OSA, so that physicians may
      be better able to determine which patients are in need of overnight PSG. 

PMID- 25570928
TI  - Axonal transport velocity estimation from kymographs based on curvilinear feature
      extraction and spline fitting.
AB  - Axonal transport velocities are obtained from spatio-temporal maps called
      kymographs developed from time-lapse confocal microscopy movies of neurons. The
      kymographs of axonal transport of C.elegans worms are much noisier due to in vivo
      nature of imaging. Existing methodologies for velocity measurement include
      laborious manual delineation of axonal movement ridges on the kymographs and
      thereby determining particle velocities from the slopes of ridges marked. Manual
      kymograph analysis is not only time consuming but also prone to human errors in
      marking the ridges. An automated algorithm to extract all the ridges and
      determine the velocities without significant manual efforts is highly preferred.
      Not many methods are currently available for such biological studies. We present
      an almost automated method based on information fusion using LDA classifier,
      morphological image processing and spline fitting for determining axonal
      transport velocities. Experimental analysis of 50 kymographs shows considerable
      reduction of 89% in time taken with manual intervention of 10.83%. Comparitive
      study with the results of two of the previous literatures shows that our
      algorithm performs better. 

PMID- 25570929
TI  - BiofilmQuant: a computer-assisted tool for dental biofilm quantification.
AB  - Dental biofilm is the deposition of microbial material over a tooth substratum.
      Several methods have recently been reported in the literature for biofilm
      quantification; however, at best they provide a barely automated solution
      requiring significant input needed from the human expert. On the contrary, state
      of-the-art automatic biofilm methods fail to make their way into clinical
      practice because of the lack of effective mechanism to incorporate human input to
      handle praxis or misclassified regions. Manual delineation, the current gold
      standard, is time consuming and subject to expert bias. In this paper, we
      introduce a new semi-automated software tool, BiofilmQuant, for dental biofilm
      quantification in quantitative light-induced fluorescence (QLF) images. The
      software uses a robust statistical modeling approach to automatically segment the
      QLF image into three classes (background, biofilm, and tooth substratum) based on
      the training data. This initial segmentation has shown a high degree of
      consistency and precision on more than 200 test QLF dental scans. Further, the
      proposed software provides the clinicians full control to fix any misclassified
      areas using a single click. In addition, BiofilmQuant also provides a complete
      solution for the longitudinal quantitative analysis of biofilm of the full set of
      teeth, providing greater ease of usability. 

PMID- 25570930
TI  - Analysis of HEp-2 images using MD-LBP and MAD-bagging.
AB  - Indirect immunofluorescence imaging is employed to identify antinuclear
      antibodies in HEp-2 cells which founds the basis for diagnosing autoimmune
      diseases and other important pathological conditions involving the immune system.
      Six categories of HEp-2 cells are generally considered, namely homogeneous, fine
      speckled, coarse speckled, nucleolar, cyto-plasmic, and centromere cells.
      Typically, this categorisation is performed manually by an expert and is hence
      both time consuming and subjective. In this paper, we present a method for
      automatically classifiying HEp-2 cells using texture information in conjunction
      with a suitable classification system. In particular, we extract multidimensional
      local binary pattern (MD-LBP) texture features to characterise the cell area.
      These then form the input for a classification stage, for which we employ a
      margin distribution based bagging pruning (MAD-Bagging) classifier ensemble. We
      evaluate our algorithm on the ICPR 2012 HEp-2 contest benchmark dataset, and
      demonstrate it to give excellent performance, superior to all algorithms that
      were entered in the competition. 

PMID- 25570931
TI  - Microscopic imaging of electrical current distribution at the electrode
      electrolyte interface.
AB  - A method to directly visualize electrical current distribution at the electrode
      electrolyte interface of a biopotential electrode is presented in this paper. A
      voltage-responsive florescent material is first coated on the surface of a
      bioelectrode. Then, an electric potential is used to activate the release of the
      florescent material while a camera acquires images at the electrode-electrolyte
      interface. This imaging method allows observation of microscopic electrical
      current distribution at the active area of the electrode, providing a new tool to
      optimize bioelectrode design. Our computational and experimental data demonstrate
      the feasibility of the florescent imaging method. 

PMID- 25570932
TI  - Toward lower contrast computer vision in vivo flow cytometry.
AB  - There are many applications in biomedical research where detection and
      enumeration of circulating cells (CCs) is important. Existing techniques involve
      drawing and enriching blood samples and analyzing them ex vivo. More recently,
      small animal "in vivo flow cytometry" (IVFC) techniques have been developed,
      where fluorescently-labeled cells flowing through small arterioles (ear, retina)
      are detected and counted. We recently developed a new high-sensitivity IVFC
      technique termed "Computer Vision(CV)-IVFC". Here, large circulating blood
      volumes were monitored in the ears of mice with a wide-field video-rate near
      infrared (NIR) fluorescent camera. Cells were labeled with a membrane dye and
      were detected and tracked in noisy image sequences. This technique allowed
      enumeration of CCs in vivo with overall sensitivity better than 10 cells/mL.
      However, an ongoing area of interest in our lab is optimization of the system for
      lower-contrast imaging conditions, e.g. when CCs are weakly labeled, or in the
      case higher background autofluorescence with visible dyes. To this end, we
      developed a new optical flow phantom model to control autofluorescence intensity
      and physical structure to better mimic conditions observed in mice. We acquired
      image sequences from a series of phantoms with varying levels of contrast and
      analyzed the distribution of pixel intensities, and showed that we could generate
      similar conditions to those in vivo. We characterized the performance of our CV
      IVFC algorithm in these phantoms with respect to sensitivity and false-alarm
      rates. Use of this phantom model in optimization of the instrument and algorithm
      under lower-contrast conditions is the subject of ongoing work in our lab. 

PMID- 25570933
TI  - Cell penetrating peptide mediated quantum dot delivery and release in live
      mammalian cells.
AB  - Quantum dots (QDs) are semiconductor nanocrystals whose unique fluorescence
      properties make them desirable biological imaging probes. However, reliable and
      efficient cellular delivery of QDs remains technically challenging. To address
      this problem, we developed a cell penetrating peptide (CPP) based approach that
      delivers QDs into mammalian cells with high reproducibility and efficiency and
      minimal cytotoxicity. To understand the delivery mechanism, we analyzed related
      cell uptake pathways. We followed internalization and endosomal release of CPP
      conjugated QDs (CPP-QDs) and found that although endocytosis (micropinocytosis)
      was the predominant pathway, some CPP-QDs were internalized through direct
      permeation of the plasma membrane. Internalized QDs could be released from
      endosomes to the cytoplasm if conjugated with an endosomolytic peptide (HA2), but
      most of released particles either were re-captured by lysosomes or aggregated in
      the cytoplasm. Together, our results provide insights into mechanisms of CPP
      mediated cellular delivery of quantum dots for intracellular imaging as well as
      therapeutic applications. 

PMID- 25570934
TI  - Techniques and applications of dynamic contrast enhanced magnetic resonance
      imaging in cancer.
AB  - We first discuss several key technical issues associated with quantitative
      dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), and then provide
      examples of DCE-MRI in oncology. In particular, we examine the importance of both
      active and passive delivery of the contrast agent to the tissue under
      investigation, and repeatability/reproducibility in DCE-MRI studies. We then
      discuss examples of how DCE-MRI can assist in assessing and predicting
      therapeutic response in the neoadjuvant setting. 

PMID- 25570935
TI  - Contrast dispersion imaging for cancer localization.
AB  - Cancer growth is associated with angiogenic processes in many types of cancer.
      Several imaging strategies have therefore been developed that target angiogenesis
      as a marker for cancer localization. To this end, intravascular and extravascular
      tissue perfusion is typically assessed by dynamic contrast enhanced (DCE)
      ultrasound (US) and MRI. All the proposed strategies, however, overlook important
      changes in the microvascular architecture that result from angiogenic processes.
      To overcome these limitations, we have recently introduced a new imaging strategy
      that analyzes the intravascular dispersion kinetics of contrast agents spreading
      through the microvasculature. Contrast dispersion is mainly determined by
      microvascular multi-path trajectories, reflecting the underlying microvascular
      architecture. This paper reviews the results obtained for prostate cancer
      localization by US and MRI dispersion imaging, also presenting the latest new
      developments and future perspectives. 

PMID- 25570936
TI  - Closed-form solution of the convolution integral in the magnetic resonance
      dispersion model for quantitative assessment of angiogenesis.
AB  - Prostate cancer (PCa) diagnosis and treatment is still limited due to the lack of
      reliable imaging methods for cancer localization. Based on the fundamental role
      played by angiogenesis in cancer growth and development, several dynamic contrast
      enhanced (DCE) imaging methods have been developed to probe tumor angiogenic
      vasculature. In DCE magnetic resonance imaging (MRI), pharmacokinetic modeling
      allows estimating quantitative parameters related to the physiology underlying
      tumor angiogenesis. In particular, novel magnetic resonance dispersion imaging
      (MRDI) enables quantitative assessment of the microvascular architecture and
      leakage, by describing the intravascular dispersion kinetics of an extravascular
      contrast agent with a dispersion model. According to this model, the tissue
      contrast concentration at each voxel is given by the convolution between the
      intravascular concentration, described as a Brownian motion process according to
      the convective-dispersion equation, with the interstitium impulse response,
      represented by a mono-exponential decay, and describing the contrast leakage in
      the extravascular space. In this work, an improved formulation of the MRDI method
      is obtained by providing an analytical solution for the convolution integral
      present in the dispersion model. The performance of the proposed method was
      evaluated by means of dedicated simulations in terms of estimation accuracy,
      precision, and computation time. Moreover, a preliminary clinical validation was
      carried out in five patients with proven PCa. The proposed method allows for a
      reduction by about 40% of computation time without any significant change in
      estimation accuracy and precision, and in the clinical performance. 

PMID- 25570937
TI  - Blind deconvolution in dynamic contrast-enhanced MRI and ultrasound.
AB  - This paper is focused on quantitative perfusion analysis using MRI and
      ultrasound. In both MRI and ultrasound, most approaches allow estimation of rate
      constants (Ktrans, kep for MRI) and indices (AUC, TTP) that are only related to
      the physiological perfusion parameters of a tissue (e.g. blood flow, vessel
      permeability) but do not allow their absolute quantification. Recent methods for
      quantification of these physiological perfusion parameters are shortly reviewed.
      The main problem of these methods is estimation of the arterial input function
      (AIF). This paper summarizes and extends the current blind-deconvolution
      approaches to AIF estimation. The feasibility of these methods is shown on a
      small preclinical study using both MRI and ultrasound. 

PMID- 25570938
TI  - The ovine corpus luteum angiogenesis model: a tool for developing imaging
      technology.
AB  - Robust tools for the quantitation of perfusion are not fully developed using
      contrast enhanced ultrasound (CEUS). The ovine corpus luteum (CL) is a transient
      gland in the ovary that is formed to produce the hormone progesterone essential
      for maintenance of pregnancy. Importantly, it has a dense microvascular network
      with predictable and well-regulated angiogenic mechanisms. In a number of
      different experiments it was shown that this property may be used to investigate
      and refine imaging methodology. Using a Philips iU22 ultrasound scanner (Philips
      Medical Systems Corp, Seattle, WA) in contrast imaging mode it was shown that a
      highly controlled experiment may produce high levels of reproducibility in the
      transit of contrast with standard uncertainty below 10%. Also, compartmental
      kinetics models were tested. The use of prostaglandin F2alpha promotes an intense
      anti-angiogenesis, allowing monitoring with CEUS prior to and following the
      demise of the CL microvasculature within 24 hours. Finally, the robust angiogenic
      property of the CL during the oestrous cycle allows further refinement of CEUS in
      vivo. In conclusion, the CL offers an attractive changing vascular bed for
      assessing existing and developing new clinically relevant perfusion imaging
      methodology. 

PMID- 25570939
TI  - The implementation of acoustic angiography for microvascular and angiogenesis
      imaging.
AB  - Recently, it has been demonstrated that through the use of contrast agents and
      multi-frequency transducer technology, high resolution and high signal to noise
      ultrasound images can be obtained which illustrate microvascular structure in
      unprecedented detail for an ultrasound modality. The enabling technology is
      ultrasound transducers which are fabricated with elements which can excite
      microbubble contrast agents near resonance and detect their broadband harmonics
      at a much higher bandwidth (several times the fundamental frequency). The
      resulting images contain very little background from tissue scattering and thus
      provide high contrast, and can have a resolution on the order of 130 microns with
      an appropriate high frequency receiving element. Because microbubbles are
      strictly an intravascular agent, this approach enables visualization of
      microvascular morphology with unique clarity, providing insight into angiogenesis
      associated with tumor development. 

PMID- 25570940
TI  - Effect of isoflurane on somatosensory evoked potentials in a rat model.
AB  - Somatosensory evoked potentials (SEPs) are widely used in the clinic as well as
      research to study the functional integrity of the different parts of sensory
      pathways. However, most general anesthetics, such as isoflurane, are known to
      suppress SEPs, which might affect the interpretation of the signals. In animal
      studies, the usage of anesthetics during SEP measurements is inevitable due to
      which detailed effect of these drugs on the recordings should be known. In this
      paper, the effect of isoflurane on SEPs was studied in a rat model. Both time and
      frequency properties of the cortical recordings generated by stimulating the
      tibial nerve of rat's hindlimb were investigated at three different isoflurane
      levels. While the anesthetic agent is shown to generally suppress the amplitude
      of the SEP, the effect was found to be nonlinear influencing more substantially
      the latter part of waveform. This finding will potentially help us in future work
      aiming at separating the effects of anesthetics on SEP from those due to injury
      in the ascending neural pathways. 

PMID- 25570941
TI  - Altered cortical causality after remifentanil administration in healthy
      volunteers: a novel approach for pharmaco-EEG.
AB  - Alterations in cortical causality information flow induced by remifentanil
      infusion in healthy volunteers was investigated in a placebo-controlled double
      blind cross-over study. For each of the 21 enrolled male subjects, 2.5 minutes of
      resting electroencephalography (EEG) data were collected before and after
      infusion of remifentanil and placebo. Additionally, to assess cognitive function
      and analgesic effect, continuous reaction time (CRT) and bone pressure and heat
      pain were assessed, respectively. The causality information was extracted from
      the EEG by phase slope index (PSI). Among the features being reproducible between
      the two baseline recordings, several PSI features were altered by remifentanil
      administration in comparison to placebo. Furthermore, several of the PSI features
      altered by remifentanil were correlated to changes in both CRT and pain scores.
      The results indicate that remifentanil administration influence the information
      flow between several brain areas. Hence, the EEG causality approach offers the
      potential to assist in deciphering the cortical effects of remifentanil
      administration. 

PMID- 25570942
TI  - Changes of symptom and EEG in mal de debarquement syndrome patients after
      repetitive transcranial magnetic stimulation over bilateral prefrontal cortex: a
      pilot study.
AB  - Mal de debarquement syndrome (MdDS) is a chronic disorder of imbalance
      characterized by a feeling of rocking and swaying. The medical treatment for MdDS
      is still limited. Motivated by our previous pilot study that demonstrates the
      promising clinical efficacy of repetitive transcranial stimulation (rTMS) in MdDS
      patients, a novel rTMS paradigm, i.e., 1 Hz stimulation over ipsilateral dorsal
      lateral prefrontal cortex (DLPFC) with respect to the dominant hand followed by
      10 Hz stimulation over contralateral DLPFC, was proposed and conducted in MdDS in
      the present study. To evaluate the potential efficacy, we examined the changes
      before and after rTMS in both subjective reported symptom using visual analogue
      scale (VAS) and direct brain activity in resting state electroencephalography
      (rsEEG). To disentangle activity from distinct brain substrates and/or local
      networks in rsEEG signals, a group-wise independent component analysis was
      employed and the corresponding spectral power changes were examined in the
      identified components. In general, reduction in rocking sensation was reported in
      five of ten subjects (with dramatic reductions (changes > 30) in three subjects)
      after rTMS using the present paradigm, while no changes and slight increases in
      rocking sensation were reported in the remaining subjects. In rsEEG, significant
      elevated spectral powers in low frequency bands (i.e., theta and alpha) over
      broad areas of occipital, parietal, motor, and prefrontal cortices were induced
      by rTMS, reflecting the enhancement of cortical inhibition over these areas.
      Meanwhile, the significant correlations between changes in rsEEG and VAS scores
      were detected in the high frequency bands (i.e., high alpha and beta) over
      posterior parietal and left visual areas, reflecting the suppression of spatial
      information processing. Therefore, the present findings demonstrate the promising
      clinical efficacy of a new rTMS paradigm for MdDS, and suggest its merit for
      further studies in more patients. 

PMID- 25570943
TI  - Interaction between EEG and drug concentration to predict response to noxious
      stimulation during sedation-analgesia: effect of the A118G genetic polymorphism.
AB  - The level of sedation in patients undergoing medical procedures is affected by
      the interaction between the effect of the anesthetic and analgesic agents and the
      pain stimuli. The presence of the A118G single nucleotide polymorphism (SNP) in
      the OPRM1 gene affects the requirements of opioids for patients undergoing
      sedation-analgesia. The purpose of this work is to evaluate the influence of the
      SNP A118G in OPRM1 on EEG measures for the prediction of the response to pain
      stimulation during endoscopy procedure. The proposed measures were based on power
      spectral density and auto-mutual information function. It was found that the
      statistical performances of the EEG measures improved when the presence of the
      SNP was taken into account (prediction probability Pk>0.9). 

PMID- 25570944
TI  - Posture-dependent changes in corticomotor excitability of the biceps after spinal
      cord injury and tendon transfer.
AB  - Following tendon transfer of the biceps to triceps after cervical spinal cord
      injuries (SCI), individuals must learn to activate the transferred biceps muscle
      to extend the elbow. Corticomotor excitability of the transferred biceps may play
      a role in post-operative elbow extension strength. In this study, we evaluated
      whether corticomotor excitability of the transferred biceps is related to an
      individuals' ability to extend the elbow, and whether posture and muscle length
      affects corticomotor excitability after SCI and tendon transfer similarly to the
      nonimpaired biceps. Corticomotor excitability was assessed in twelve nonimpaired
      arms and six arms of individuals with SCI and biceps-to-triceps transfer using
      transcranial magnetic stimulation (TMS) delivered at rest. Maximum isometric
      elbow extensor moments were recorded in transferred arms and the fiber length of
      the transferred biceps was estimated using a musculoskeletal model. Across the
      SCI subjects, corticomotor excitability of the transferred biceps increased with
      elbow extension strength. Thus, rehabilitation to increase excitability may
      enhance strength. Excitability of the transferred biceps was not related to fiber
      length suggesting that similar to nonimpaired subjects, posture-dependent changes
      in biceps excitability are primarily centrally modulated after SCI. All
      nonimpaired biceps were most excitable in a posture in the horizontal plane with
      the forearm fully supinated. The proportion of transferred biceps in which
      excitability was highest in this posture differed from the nonimpaired group.
      Therefore, rehabilitation after tendon transfer may be most beneficial if
      training postures are tailored to account for changes in biceps excitability. 

PMID- 25570945
TI  - Modelling of deep transcranial magnetic stimulation: different coil
      configurations.
AB  - This paper provides a characterization of the induced electric field
      distributions in the brain of a realistic human model due to 16 different coil
      configurations. We used the scalar potential finite element method to calculate
      the induced electric field distributions differentiating the brain structures,
      e.g. cortex, white matter, cerebellum, thalamus, hypothalamus, hippocampus, pons
      and midbrain. We found that, despite the presence of a depth-focality tradeoff,
      some configurations are able to reach subcortical white matter tracts at
      effective electric field level. 

PMID- 25570946
TI  - Heterogeneous postsurgical data analytics for predictive modeling of mortality
      risks in intensive care units.
AB  - The rapid advancements of biomedical instrumentation and healthcare technology
      have resulted in data-rich environments in hospitals. However, the meaningful
      information extracted from rich datasets is limited. There is a dire need to go
      beyond current medical practices, and develop data-driven methods and tools that
      will enable and help (i) the handling of big data, (ii) the extraction of data
      driven knowledge, (iii) the exploitation of acquired knowledge for optimizing
      clinical decisions. This present study focuses on the prediction of mortality
      rates in Intensive Care Units (ICU) using patient-specific healthcare recordings.
      It is worth mentioning that postsurgical monitoring in ICU leads to massive
      datasets with unique properties, e.g., variable heterogeneity, patient
      heterogeneity, and time asyncronization. To cope with the challenges in ICU
      datasets, we developed the postsurgical decision support system with a series of
      analytical tools, including data categorization, data pre-processing, feature
      extraction, feature selection, and predictive modeling. Experimental results show
      that the proposed data-driven methodology outperforms traditional approaches and
      yields better results based on the evaluation of real-world ICU data from 4000
      subjects in the database. This research shows great potentials for the use of
      data-driven analytics to improve the quality of healthcare services. 

PMID- 25570947
TI  - Parallel computing simulation of electrical excitation and conduction in the 3D
      human heart.
AB  - A correctly beating heart is important to ensure adequate circulation of blood
      throughout the body. Normal heart rhythm is produced by the orchestrated
      conduction of electrical signals throughout the heart. Cardiac electrical
      activity is the resulted function of a series of complex biochemical-mechanical
      reactions, which involves transportation and bio-distribution of ionic flows
      through a variety of biological ion channels. Cardiac arrhythmias are caused by
      the direct alteration of ion channel activity that results in changes in the AP
      waveform. In this work, we developed a whole-heart simulation model with the use
      of massive parallel computing with GPGPU and OpenGL. The simulation algorithm was
      implemented under several different versions for the purpose of comparisons,
      including one conventional CPU version and two GPU versions based on Nvidia CUDA
      platform. OpenGL was utilized for the visualization / interaction platform
      because it is open source, light weight and universally supported by various
      operating systems. The experimental results show that the GPU-based simulation
      outperforms the conventional CPU-based approach and significantly improves the
      speed of simulation. By adopting modern computer architecture, this present
      investigation enables real-time simulation and visualization of electrical
      excitation and conduction in the large and complicated 3D geometry of a real
      world human heart. 

PMID- 25570948
TI  - Effects of macroscopic heterogeneity on propagation in a computationally
      inexpensive 2D model of the heart.
AB  - We have developed a computationally inexpensive, two-dimensional, bidomain model
      of the heart to demonstrate the effect of tissue heterogeneity on propagation of
      cardiac impulses generated by the sino-atrial node (SAN). The geometry consists
      of a thin sheet of cardiac tissue with designated areas that represent the SAN
      and atria. The SAN auto-generates continuous impulses that result in waves of
      normal propagation throughout the tissue. On the introduction of heterogeneous
      patches with low tissue conductivities, the rhythm of the waveform becomes
      irregular. The study suggests that simplified and computationally inexpensive
      models can be insightful tools to better understand the mechanisms that cause
      atrial fibrillation (AF) and hence more effective treatment methods. 

PMID- 25570949
TI  - Electrophysiological properties under heart failure conditions in a human
      ventricular cell: a modeling study.
AB  - Heart failure (HF) is one of the major diseases across the world. During HF the
      electrophysiology of the failing heart is remodeled, which renders the heart more
      susceptible to ventricular arrhythmias. In this study, we quantitatively analyze
      the effects of electrophysiological remodeling of the major currents of human
      ventricular myocytes on the dynamics of the failing heart. We develop a HF model
      using a modified version of a recently published model of the human ventricular
      action potential, the O'Hara-Virag-Varro-Rudy (OVVR) model. The proposed HF model
      incorporates recently available HF clinical data. It can reproduce most of the
      action potential (AP) properties of failing myocytes, including action potential
      duration (APD), amplitude (APA), notch (APN), plateau (APP), resting membrane
      potential (RMP), and maximum upstroke velocity (dV/dtmax). In addition, the model
      reproduces the behavior of the [Na+], concentration and [Ca(2)+]i dynamics.
      Moreover, the HF model exhibits alternans with a fast pacing frequency and can
      induce early afterdepolarizations (EADs). Additionally, blocking the late sodium
      current shortens the APD and suppresses EADs, in agreement with experimental
      findings. The dynamics of the proposed model are assessed through investigating
      the rate dependence of the AP and the dynamics of the major currents. The steady
      state (S-S) and S1-S2 restitution curves along with accommodation to an abrupt
      change in cycle length were evaluated. Our study should help to elucidate the
      roles of alterations in electrophysiological properties during HF. Also, this HF
      cellular model could be used to study HF in a realistic geometry and could be
      embedded into a model of HF electromechanics to investigate electrical and
      mechanical properties simultaneously during HF. 

PMID- 25570950
TI  - A theoretical analysis of the electrogastrogram (EGG).
AB  - In this study, a boundary element model was developed to investigate the
      relationship between the gastric electrical activity, also known as slow waves,
      and the electrogastrogram (EGG). A dipole was calculated to represent the
      equivalent net activity of gastric slow waves. The dipole was then placed in an
      anatomically-realistic torso model to simulate EGG. The torso model was
      constructed from a laser-scanned geometry of an adult male torso phantom with 190
      electrode sites equally distributed around the torso so that simulated EGG could
      be directly compared between the physical model and the mathematical model. The
      results were analyzed using the Fast Fourier Transforms (FFT), spatial
      distribution of EGG potential and a resultant EGG based on a 3-lead
      configuration. The FFT results showed both the dipole and EGG contained identical
      dominant frequency component of 3 cycles per minute (cpm), with this result
      matching known physiological phenomenon. The -3 dB point of the EGG was 110 mm
      from the region directly above the dipole source. Finally, the results indicated
      that electrode coupling could theoretically be used in a similar fashion to ECG
      coupling to gain greater understanding of how EGG correlate to gastric slow
      waves. 

PMID- 25570951
TI  - Parameters analysis of FitzHugh-Nagumo model for a reliable simulation.
AB  - Derived from the pioneer ionic Hodgkin-Huxley model and due to its simplicity and
      richness from a point view of nonlinear dynamics, the FitzHugh-Nagumo model (FHN)
      is one of the most successful simplified neuron / cardiac cell model. There exist
      many variations of the original FHN model. Though these FHN type models help to
      enrich the dynamics of the FHN model, the parameters used in these models are
      often in biased conditions. The related results would be questionable. So, in
      this study, the aim is to find the parameter thresholds for one of the commonly
      used FHN model in order to provide a better simulation environment. The results
      showed at first that inappropriate time step and integration tolerance in
      numerical solution of FHN model can give some biased results which would make
      some publications questionable. Then the thresholds of parameters alpha, gamma
      and epsilon are presented. alpha controls the global dynamics of FHN. alpha > 0,
      the cell is in refractory mode; alpha <; 0, the cell is excitable. epsilon
      controls the main morphology of the action potential generated and has a relation
      with the period (P = 3.065 * alphaalpha,gamma(-0.8275)+ 4.397). To show
      oscillations of relaxation with FHN, epsilon should be smaller than 0.0085. 7
      influences barely action potential, it showed linear relationship with the period
      and duration of action potential. Even though alpha <; 0.1, epsilon <; 0.0085,
      there is no definite threshold for gamma, smaller values are recommended. 

PMID- 25570952
TI  - Upper extremity biomechanics of children with spinal cord injury during
      wheelchair mobility.
AB  - While much work is being done evaluating the upper extremity joint dynamics of
      adult manual wheelchair propulsion, limited work has examined the pediatric
      population of manual wheelchair users. Our group used a custom pediatric
      biomechanical model to characterize the upper extremity joint dynamics of 12
      children and adolescents with spinal cord injury (SCI) during wheelchair
      propulsion. Results show that loading appears to agree with that of adult manual
      wheelchair users, with the highest loading primarily seen at the glenohumeral
      joint. This is concerning due to the increased time of wheelchair use in the
      pediatric population and the impact of this loading during developmental years.
      This research may assist clinicians with improved mobility assessment methods,
      wheelchair prescription, training, and long-term care of children with
      orthopaedic disabilities. 

PMID- 25570953
TI  - Non-invasive assessment of soft-tissue artefacts in hip joint kinematics using
      motion capture data and ultrasound depth measurements.
AB  - In human movement analysis, the hip joint centre can be estimated using a
      functional method based on the relative motion of the femur to the pelvis
      measured using reflective markers attached to the skin surface by an optical
      motion capture system. The principal source of errors in estimating the hip joint
      centre location using functional methods is soft tissue artefacts due to the
      relative motion between the markers and bone; one of the main objectives in human
      movement analysis is the assessment of soft tissue artefact. Various studies have
      described the movement of soft tissue artefact and compensated for it invasively;
      examples include: intra-cortical pins, external fixators, percutaneous skeletal
      trackers, and Roentgen photogrammetry. The goal of this study is to present a non
      invasive method to assess soft tissue artefact using optical motion capture data
      and tissue thickness from ultrasound measurements during flexion and abduction
      (both with the knee extended) of the hip joint. Results showed that the skin
      marker displacements caused by the artefact are non-linear and larger in areas
      closer to the hip joint. It was also found that the marker displacements are
      dependent on the movement type and relatively larger in abduction movement. 

PMID- 25570954
TI  - Biomechanical evaluation of pedicle screw loosening mechanism using synthetic
      bone surrogate of various densities.
AB  - Pedicle screw fixation is a well-established procedure for various spinal
      disorders. However, pedicle screws failures are still reported. Therefore, there
      is a need for a greater understanding of the pedicle screw failure mechanism.
      This experimental study investigates the biomechanical stability of pedicle
      screws using a synthetic bone surrogate with a special focus on the screw
      loosening mechanism. Pedicle screws have been inserted in thirty six polyurethane
      foam blocks of three different densities. In half of the specimens from each
      density group, pedicle screws were submitted to cyclic bending (toggling) before
      pullout. The rest of specimens were solely loaded in axial pullout. The peak
      pullout force and stiffness were determined from load-displacement curve of each
      specimen. Statistical analyses were performed to investigate on the effect of
      toggling and bone surrogate density on the pedicle screw's pullout force. The
      results suggest that the pullout force and stiffness were significantly affected
      by toggling and density. Higher pullout forces resulted from higher grades of
      density. The proposed method allowed investigating the pedicle screw loosening
      mechanism. However, conducing further experimental tests on animal or cadaveric
      vertebrae are needed to confirm these findings. 

PMID- 25570955
TI  - Estimation of pedicle screw fixation strength from probe indentation force and
      screw insertion torque: a biomechanical study on bone surrogates of various
      densities.
AB  - Posterior pedicle screw fixation is commonly used for patients with spinal
      disorders. However, failure of fixation is reported in many cases and surgeons
      have only little information. The objective of this study was to assess the
      correlation between the probe indentation force, screw insertion torque and the
      pullout force using bone surrogates of different densities. The indentation force
      and insertion torque were measured using a custom made test bench during screw
      insertion into polyurethane foam blocks. The two variables were significantly
      correlated to pullout force and to density. A high correlation was also found
      between indentation force and the peak insertion torque. The proposed methods for
      measuring indentation force and screw insertion torque were reproducible. This
      study suggests that the peak screw insertion torque and the indentation force can
      predict the screw fixation strength in synthetic bone models. Additional tests
      should be performed on animal and human specimens to confirm and to translate
      these findings to clinical applications. 

PMID- 25570957
TI  - Development of three-dimensional motion measuring device for the human ankle
      joint by using parallel link mechanism.
AB  - This paper presents a novel ankle motion measuring device that can measure three
      dimensional motions without a motion capture system (MCS). We adapted a parallel
      link mechanism for the device using six wire-type displacement sensors to measure
      the ankle joint motions in six degrees of freedom (six-DOF). We define the
      motions of a foot plate which is attached to a foot sole as ankle joint motions.
      A posture of the foot plate, i.e., the three-dimensional position (x, y, z) and
      rotation angle (theta, Phi, psi), is numerically calculated by solving the
      forward kinematics of the developed device. We conducted performance verification
      experiments of the developed device by comparing these results with those of the
      MCS. The experimental results show that the maximum root mean square error of the
      three-dimensional position and rotation angle measured by the developed device
      are 2.6 mm and 1.5 degrees , respectively. This measuring performance of the
      developed device indicates that the ankle motion measuring device is accurate and
      valid. Moreover, this device enables physical therapists to easily measure ankle
      motions with an accuracy as high as that of an MCS. 

PMID- 25570956
TI  - Thumb carpometacarpal joint congruence during functional tasks and thumb range-of
      motion activities.
AB  - Joint incongruity is often cited as a possible etiological factor for the high
      incidence of thumb carpometacarpal (CMC) joint osteoarthritis (OA) in older
      women. There is evidence suggesting that biomechanics plays a role in CMC OA
      progression, but little is known about how CMC joint congruence, specifically,
      differs among different cohorts. The purpose of this in vivo study was to
      determine if CMC joint congruence differs with sex, age, and early stage OA for
      different thumb positions. Using CT data from 155 subjects and a congruence
      metric that is based on both articular morphology and joint posture, we did not
      find any differences in CMC joint congruence with sex or age group, but found
      that patients in the early stages of OA exhibit lower congruence than healthy
      subjects of the same age group. 

PMID- 25570959
TI  - Multifunction myoelectric control using multi-dimensional dynamic time warping.
AB  - Myoelectric control can be used for a variety of applications including powered
      protheses and different human computer interface systems. The aim of this study
      is to investigate the formulation of myoelectric control as a multi-class
      distance-based classification of multidimensional sequences. More specifically,
      we investigate (1) estimation of multi-muscle activation sequences from multi
      channel electromyographic signals in an online manner, and (2) classification
      using a distance metric based on multi-dimensional dynamic time warping. Subject
      specific results across 5 subjects executing 10 different hand movements showed
      an accuracy of 95% using offline extracted trajectories and an accuracy of 84%
      using online extracted trajectories. 

PMID- 25570958
TI  - Natural control capabilities of robotic hands by hand amputated subjects.
AB  - People with transradial hand amputations who own a myoelectric prosthesis
      currently have some control capabilities via sEMG. However, the control systems
      are still limited and not natural. The Ninapro project is aiming at helping the
      scientific community to overcome these limits through the creation of publicly
      available electromyography data sources to develop and test machine learning
      algorithms. In this paper we describe the movement classification results gained
      from three subjects with an homogeneous level of amputation, and we compare them
      with the results of 40 intact subjects. The number of considered subjects can
      seem small at first sight, but it is not considering the literature of the field
      (which has to face the difficulty of recruiting trans-radial hand amputated
      subjects). The classification is performed with four different classifiers and
      the obtained balanced classification rates are up to 58.6% on 50 movements, which
      is an excellent result compared to the current literature. Successively, for each
      subject we find a subset of up to 9 highly independent movements, (defined as
      movements that can be distinguished with more than 90% accuracy), which is a
      deeply innovative step in literature. The natural control of a robotic hand in so
      many movements could lead to an immediate progress in robotic hand prosthetics
      and it could deeply change the quality of life of amputated subjects. 

PMID- 25570960
TI  - Covariate shift adaptation in EMG pattern recognition for prosthetic device
      control.
AB  - Ensuring robustness of myocontrol algorithms for prosthetic devices is an
      important challenge. Robustness needs to be maintained under nonstationarities,
      e.g. due to electrode shifts after donning and doffing, sweating, additional
      weight or varying arm positions. Such nonstationary behavior changes the signal
      distributions - a scenario often referred to as covariate shift. This
      circumstance causes a significant decrease in classification accuracy in daily
      life applications. Re-training is possible but it is time consuming since it
      requires a large number of trials. In this paper, we propose to adapt the EMG
      classifier by a small calibration set only, which is able to capture the relevant
      aspects of the nonstationarities, but requires re-training data of only very
      short duration. We tested this strategy on signals acquired across 5 days in able
      bodied individuals. The results showed that an estimator that shrinks the
      training model parameters towards the calibration set parameters significantly
      increased the classifier performance across different testing days. Even when
      using only one trial per class as re-training data for each day, the
      classification accuracy remained > 92% over five days. These results indicate
      that the proposed methodology can be a practical means for improving robustness
      in pattern recognition methods for myocontrol. 

PMID- 25570961
TI  - Discrete vs. continuous surface electromyographic interface control.
AB  - Over 50% of the 273,000 individuals with spinal cord injuries in the US have
      cervical injuries and are therefore unable to operate a keyboard and mouse with
      their hands. In this experiment, we compared two systems using surface
      electromyography (sEMG) recorded from facial muscles to control an onscreen
      keyboard. Both systems used five sEMG sensors to capture muscle activity during
      five distinct facial gestures that then mapped to five cursor commands: move
      left, move right, move up, move down, and click. One system used a discrete
      movement and feedback algorithm, in which the user would make one quick facial
      gesture, causing a corresponding discrete movement to an adjacent button. The
      other system was continuously updated and allowed the user to move in any 360(o)
      direction smoothly. Information transfer rates (ITRs) in bits per minute were
      high for both systems. Users of the continuous system showed significantly higher
      ITRs (average of 68.5; p <; 0.02) compared to users of the discrete system
      (average of 54.3 bits/min). 

PMID- 25570962
TI  - Posture muscle relationship with cardiovascular changes under orthostatic
      challenge.
AB  - Lower leg muscles are known to be activated during standing. On the other hand,
      standing is known to induce orthostatic stress. Our recent work presented that
      the posture control and cardiovascular systems are related to each other.
      However, the relationship of the individual muscle activation with blood pressure
      changes is not fully understood. The present preliminary study conducted
      experiments to collect data for muscle activation (EMG) and blood pressure (BP)
      changes during quiet standing. High coherence (>threshold) values observed
      between the EMG and BP signals suggest a strong relationship between the two.
      Additionally, the results of the study suggest a compensatory relationship of
      different lower leg muscles with blood pressure changes during quiet standing. 

PMID- 25570964
TI  - Control of finger forces during fast, slow and moderate rotational hand
      movements.
AB  - The goal of this study was to investigate the effect of speed on patterns of grip
      forces during twisting movement involving forearm supination against a torsional
      load (combined elastic and inertial load). For slow and moderate speed rotations,
      the grip force increased linearly with load torque. However, for fast rotations
      in which the contribution of the inertia to load torque was significantly greater
      than slower movements, the grip force-load torque relationship could be segmented
      into two phases: a linear ascending phase corresponding to the acceleration part
      of the movement followed by a plateau during deceleration. That is, during the
      acceleration phase, the grip force accurately tracked the combined elastic and
      inertial load. However, the coupling between grip force and load torque was not
      consistent during the deceleration phase of the movement. In addition, as speed
      increased, both the position and the force profiles became smoother. No
      differences in the baseline grip force, safety margin to secure the grasp during
      hold phase or the overall change in grip force were observed across different
      speeds. 

PMID- 25570963
TI  - Quantification of muscle-derived signal interference during monopolar needle
      electromyography of a peripheral nerve interface in the rat hind limb.
AB  - High-fidelity signal acquisition is critical for the fundamental control of a
      neuroprosthesis. Our group has developed a bio-artificial interface consisting of
      a muscle graft neurotized by a severed nerve in a rat hind limb model. This
      regenerative peripheral nerve interface (RPNI) permits nerve signal transmission,
      amplification, and detection via in situ electromyography (EMG). Our study
      examined the magnitude of signal interference from simultaneously contracting
      muscles adjacent to our muscle of interest. In eighteen F344 rats, the extensor
      digitorum longus (EDL) muscle was used to fabricate simulated RPNI constructs of
      various sizes in which the neurovascular pedicle was preserved, obviating the
      need for reinnervation or revascularization. After 3 weeks of recovery, in situ
      EMG testing was performed using electrical stimulation of the common peroneal
      nerve. A recording needle was placed in the EDL muscle with a reference/ground
      electrode in the contralateral toe webspace, comprising a monopolar recording
      configuration. The superficial peroneal nerve was transected to further isolate
      stimulation of the anterior compartment. Recordings from the EDL were performed
      before and after excision of the tibialis anterior (TA) and extensor hallucis
      longus (EHL) muscles. After TA/EHL excision, EDL compound muscle action potential
      (CMAP) peak-to-peak amplitudes were significantly lower by an average of 7.4+/
      5.6(SD) mV, or 32+/-18%, (paired t(17)=-5.7, p<;0.0001). A significant positive
      linear correlation was seen between CMAP amplitude and EDL mass both before
      TA/EHL excision (r=0.68, n=18, p<;0.01) and after TA/EHL excision (r=0.79, n=18,
      p<;0.0001). EDL mass did not correlate with differences in CMAP amplitude or area
      caused by TA/EHL excision. Monopolar needle EMG recordings from the EDL muscle
      are significantly, but predictively, contaminated by concomitant muscular
      contractions in the anterior compartment of the rat hind limb. Further
      investigation of strategies to reduce this signal interference, including
      electrode choice or configuration, use of bioelectrical insulators, and filtering
      methods, is warranted to promote high-fidelity signal acquisition for prosthetic
      control. 

PMID- 25570966
TI  - Reciprocal inhibition becomes facilitation after spinal cord injury: clinical
      application of a system identification approach.
AB  - Alteration in spinal inputs from descending pathways following spinal cord injury
      (SCI) affects different mechanisms including reciprocal Ia inhibition. However,
      whether there is a consistent pattern of change in reciprocal inhibition
      following SCI is uncertain. Typical attempts to evaluate reciprocal inhibition
      have been restricted to electrophysiological measurements, which may have limited
      translation to function. Our objective was to address the uncertainty regarding
      changes in reciprocal inhibition after SCI by quantitatively evaluating
      reciprocal inhibition of ankle extensors from ankle flexors using our novel, more
      functionally relevant system identification approach. To evaluate reciprocal
      inhibition using the system identification technique, a series of small-amplitude
      PseudoRandom Binary Sequence (PRBS) perturbations were applied to the ankle when
      subjects contracted their dorsiflexors. Depression of reflex stiffness with
      tibialis anterior (TA) activation was evaluated as reciprocal inhibition. Our
      results showed that reflex stiffness decreased continuously as dorsiflexor torque
      increased in the healthy control subjects whereas it remained almost unchanged in
      the SCI subjects, indicating the absence of reciprocal inhibition in patients.
      This pattern was consistent with the results obtained from electrophysiological
      measures in a exploratory control experiment revealing depression of the control
      H-reflex but no change to the SCI H-reflex. These findings suggest that our
      system identification mechanical technique is a reliable and valid approach for
      evaluating reciprocal inhibition. Furthermore, our results demonstrate that
      reciprocal inhibition can diminish or change to reciprocal facilitation after
      SCI, which in turn can result in reflex hyperexcitability and unwanted activity
      of ankle extensors triggered by TA activity. This suggests that reciprocal
      facilitation may play a major role in pathophysiology of spasticity and impaired
      function. 

PMID- 25570965
TI  - High frequency activity correlates of robust movement in humans.
AB  - The neural circuitry underlying fast robust human motor control is not well
      understood. In this study we record neural activity from multiple stereotactic
      encephalograph (SEEG) depth electrodes in a human subject while he/she performs a
      center-out reaching task holding a robotic manipulandum that occasionally
      introduces an interfering force field. Collecting neural data from humans during
      motor tasks is rare, and SEEG provides an unusual opportunity to examine neural
      correlates of movement at a millisecond time scale in multiple brain regions.
      Time-frequency analysis shows that high frequency activity (50-150 Hz) increases
      significantly in the left precuneus and left hippocampus when the subject is
      compensating for a perturbation to their movement. These increases in activity
      occur with different durations indicating differing roles in the motor control
      process. 

PMID- 25570967
TI  - Causal analysis of cortical networks involved in reaching to spatial targets.
AB  - The planning of goal-directed movement towards targets in different parts of
      space is an important function of the brain. Such visuo-motor planning and
      execution is known to involve multiple brain regions, including visual, parietal,
      and frontal cortices. To understand how these brain regions work together to both
      plan and execute goal-directed movement, it is essential to describe the dynamic
      causal interactions among them. Here we model causal interactions of distributed
      cortical source activity derived from non-invasively recorded EEG, using a
      combination of ICA, minimum-norm distributed source localization (cLORETA), and
      dynamical modeling within the Source Information Flow Toolbox (SIFT). We
      differentiate network causal connectivity of reach planning and execution, by
      comparing the causal network in a speeded reaching task with that for a control
      task not requiring goal-directed movement. Analysis of a pilot dataset (n=5)
      shows the utility of this technique and reveals increased connectivity between
      visual, motor and frontal brain regions during reach planning, together with
      decreased cross-hemisphere visual coupling during planning and execution,
      possibly related to task demands. 

PMID- 25570968
TI  - Estimation of intrinsic joint impedance using quasi-static passive and dynamic
      methods in individuals with and without Cerebral Palsy.
AB  - Modeling the passive behavior of the knee in subjects with spasticity involves
      the applied external torques (e.g. gravitational torque), the intrinsic moments
      due to tissue properties, as well as active, neurally defined moments resulting
      from the hypersensitivity of reflexes introduced by disability. In order to
      provide estimates of the necessary intrinsic terms in the equation of motion, the
      push-pull and Wartenberg Pendulum Knee Drop (PKD) tests were administered. Four
      subjects without disability and two subjects with Cerebral Palsy (CP) were
      evaluated for their active and intrinsic knee stiffness parameters. Separation of
      these two terms requires an additional stiffness term be added to the traditional
      equation of motion. This holds true for subjects with and without neurological
      disability. Very interestingly, the optimized non-disabled PKD produced lumped
      stiffness (K) that is similar to the push-pull passive stiffness (KI) for both
      populations. On the other hand the optimized K value in the PKD test for subjects
      with disability was approximately 19 times larger than the KI value found
      graphically from the push-pull test. This leads us to the conclusion that we can
      partition our lumped K as the sum of a neurally generated stiffness (Ka) and KI
      to complete the trajectory model. Therefore, this study shows that spasticity is
      a velocity dependent, that would not appear in disabled individuals unless the
      examined limb has a non-zero velocity. 

PMID- 25570969
TI  - Human-human physical interaction in the joint control of an underactuated virtual
      object.
AB  - Human-human physical interaction has proven to be advantageous especially in
      contexts with high coordination requirements. But under which conditions can
      haptic communication bring to performance benefits in a challenging cooperative
      environment? In this work we investigate which are the dynamics that intervene
      when two subjects are required to switch from a bimanual to a dyadic
      configuration in order to solve a complex reaching and stabilization task of a
      virtual tool in the presence of an unstable dynamics. Results show that dyadic
      cooperation can improve the performance respect to the individual condition,
      while minimizing the effort. However, in the joint task, when the stiffness of
      the system becomes harder to manipulate the feedback delays appear to be critical
      in determining the maximum achievable level of performance. 

PMID- 25570970
TI  - An integrated passive-flow microfluidic biosensor with organic photodiodes for
      ultra-sensitive pathogen detection in water.
AB  - This work reports on integrated passive-flow optical microfluidic devices to
      detect waterborne pathogens in the field. Ring-shaped organic photodiodes were
      integrated to a capillary-induced flow microfluidic channel for monitoring
      chemiluminescent sandwich immunoassays enhanced by gold nanoparticles. The
      integrated device yielded a resolution of 4*10(4) cells/mL for the detection of
      Legionella pneumophila, which represented a 25-fold improvement over
      chemiluminescence detection devices employing no gold-nanoparticle enhancement.
      This work demonstrates the feasibility of a low-cost but highly sensitive lab-on
      a-chip device amenable for point-of-use applications. 

PMID- 25570971
TI  - Fabrication and characterization of a microfluidic module for chemical gradient
      generation utilizing passive pumping.
AB  - We introduce a micro-biochemical administration module (MUBAM) for generating
      chemical gradients for use in axonal guidance studies. The device is designed to
      be simple to use, require minimal packaging, and be operated using only a
      pipette. A passive pumping mechanism is utilized to pump liquid through a SU-8
      microchannel and then the micropore on the Parylene cap of the microchannel. The
      achievable flow rate delivery through the micropore was characterized and
      manipulated by varying the drop volumes used to passively drive fluid flow into
      the device. Biochemicals controllably delivered using this module can be combined
      with neuronal cell cultures to form chemical gradients for axonal guidance
      studies. 

PMID- 25570972
TI  - Measurement and analysis of internal stress distributions created in gelatin
      simulated-brain tissue by a pulsed laser-induced liquid jet.
AB  - Transsphenoidal surgery is currently employed to treat complex lesions beyond the
      sella turcica; however, the procedure can be limited by difficulties encountered
      in dealing with small blood vessels, deep and narrow working spaces, and awkward
      working angles. To overcome these problems, we have developed a pulsed laser
      induced liquid jet system that can dissect tumor tissue while preserving fine
      blood vessels within deep and narrow working spaces. We have previously evaluated
      the utility and safety of this procedure. However, the effects of the pulsejet
      after being injected into the brain are not yet well understood. Especially, the
      behavior of the stress distribution created by the jet is important because it
      has recently been reported that high acoustic pressures can affect the brain. In
      this study, we measured internal stress distributions in a gelatin simulated
      brain using photoelasticity experiments. We used a high-speed camera with an
      image sensor on which an array of micropolarizers was attached to measure the
      stresses and the shear wave created when the pulsejet enters the simulated brain.

PMID- 25570973
TI  - Design and analysis of a low actuation voltage electrowetting-on-dielectric
      microvalve for drug delivery applications.
AB  - This paper presents a low actuation voltage microvalve with optimized insulating
      layers that manipulates a conducting ferro-fluid droplet by the principle of
      electrowetting-on-dielectric (EWOD). The proposed EWOD microvalve contains an
      array of chromium (Cr) electrodes on the soda-lime glass substrate, covered by
      both dielectric and hydrophobic layers. Various dielectric layers including Su-8
      2002, Polyvinylidenefluoride (PVDF) and Cyanoethyl pullulan (CEP), and thin (50
      nm) hydrophobic Teflon and Cytonix are used to analyze the EWOD microvalves at
      different voltages. The Finite Element Method (FEM) based software, Coventorware
      is used to carry out the simulation analysis. It is observed that the EWOD
      microvalve having a CEP dielectric layer with dielectric constant of about 20 and
      thickness of 1 MUm, and a Cytonix hydrophobic layer with thickness of 50 nm
      operated the conducting ferro-fluid droplet at the actuation voltage as low as
      7.8 V. 

PMID- 25570974
TI  - MWCNTs-like protection layer formation on bacterial cellulose bundles as a
      potential material for suspended resonator.
AB  - Suspended carbon naotubes (CNTs) resonator is a sensitive detector for chemical
      and biological applications. Small sizes of CNTs can enhance sensitivity, but
      increase complexity for fabrication. In order to overcome the challenges, a novel
      technique has been developed to produce a long, sensitive and high tensile
      strength carbon nanotubes (CNT) coated bacterial cellulose (BC) bundle. This
      study demonstrates the use of ultrasonication to perform carboxyl functionalized
      multi-walled carbon nanotubes (MWCNTs-COOH) self-assembling on the surface of BC
      bundles (BC/MWCNTs) via hydrogen bonds. Ultrasonication can disrupt dense
      cellulose network and produce the long BC/MWCNTs bundles ranging from 30 to 100
      MUm. Raman spectroscopy shows a drop at peak of hydroxyl (-OH, 3700 m(-1)) and
      carbonyl (C=O, 1600 cm(-1)). This indicates the formation of the continuous
      MWCNTs-like protection layer on BC surface. Electrical properties of the
      BC/MWCNTs bundles showed linearity from -6 V to +6 V. Composites with BC treated
      by higher ultrasonic powers, 100 W, show higher conductivity comparing to 80 W.
      Sensitivity from 10(-7) to 10(-9) A of long BC/MWCNTs composite bundles is
      reported in this paper. This technique may be competitive to the current state of
      carbon nanotubes resonator. 

PMID- 25570975
TI  - Separation and capture of circulating tumor cells from whole blood using a bypass
      integrated microfluidic trap array.
AB  - We report on a microfluidic trap array that separates and captures circulating
      tumor cells (CTCs) from whole blood. The device is a series array of microfluidic
      branches that utilizes the difference in flow rates between the bypass channel
      and the trap channel to allow CTCs in whole blood to be separated and trapped.
      Once a trap has captured a cell with diameter larger than the narrow trap outlet,
      additional cells arriving at the branch would flow towards the bypass channel due
      to its lower flow resistance. Results demonstrated that it was possible to
      capture CTCs from the whole blood of a mouse with full-blown metastasis. With
      further developments, the bypass integrated microfluidic trap array could become
      a useful tool for the early prognosis of cancer metastasis. 

PMID- 25570976
TI  - SpikeGUI: software for rapid interictal discharge annotation via template
      matching and online machine learning.
AB  - Detection of interictal discharges is a key element of interpreting EEGs during
      the diagnosis and management of epilepsy. Because interpretation of clinical EEG
      data is time-intensive and reliant on experts who are in short supply, there is a
      great need for automated spike detectors. However, attempts to develop general
      purpose spike detectors have so far been severely limited by a lack of expert
      annotated data. Huge databases of interictal discharges are therefore in great
      demand for the development of general-purpose detectors. Detailed manual
      annotation of interictal discharges is time consuming, which severely limits the
      willingness of experts to participate. To address such problems, a graphical user
      interface "SpikeGUI" was developed in our work for the purposes of EEG viewing
      and rapid interictal discharge annotation. "SpikeGUI" substantially speeds up the
      task of annotating interictal discharges using a custom-built algorithm based on
      a combination of template matching and online machine learning techniques. While
      the algorithm is currently tailored to annotation of interictal epileptiform
      discharges, it can easily be generalized to other waveforms and signal types. 

PMID- 25570977
TI  - Automated localization of the seizure focus using interictal intracranial EEG.
AB  - Up to 30% of epileptic patients have seizures poorly controlled with anti
      epileptic drugs alone. Surgical therapy might be beneficial to patients who
      respond poorly to drug treatments. It is therefore crucial to accurately localize
      the seizure focus. Neurologists rely heavily on seizures to determine the focus.
      The invasive recordings usually continue for days or weeks, which is costly and
      entails significant risk for the patients. In this paper, techniques are
      developed to localize the seizure focus using brief interictal intracranial EEG
      (iEEG). A supervised learning paradigm is utilized making use of features
      extracted from interictal iEEG on multiple referential montages. Analysis of 14
      epileptic patients (implanted with depth electrodes) shows that iEEG features
      such as slowing, ripples, spikes, and local synchrony measures are strongly
      correlated to the seizure focus. These procedures may allow reliable localization
      of the seizure focus from brief interictal iEEG, which in turn may lead to
      shorter hospitalizations. 

PMID- 25570978
TI  - Seizure detection using wavelet decomposition of the prediction error signal from
      a single channel of intra-cranial EEG.
AB  - This paper presents a novel patient-specific algorithm for detection of seizures
      in epileptic patients from a single-channel intra-cranial electroencephaolograph
      (iEEG) recording. Instead of extracting features from the EEG signal, first the
      EEG signal is filtered by a prediction error filter (PEF) to compute a prediction
      error signal. A two-level wavelet decomposition of the prediction error signal
      leads to two detail signals and one approximate signal. Eight features are
      extracted every one second using a 2-second window with a 50% overlap. These
      features are input to two different types of classifiers: a linear support vector
      machine (SVM) classifier and an AdaBoost classifier. The algorithm is tested
      using the intra-cranial EEG (iEEG) from the Freiburg database. It is shown that
      the proposed algorithm can achieve a sensitivity of 95.0% and an average false
      positive rate (FPR) of 0.124 per hour, using the linear SVM classifier. The
      AdaBoost classifier achieves a sensitivity of 98.75% and an average FPR of 0.075
      per hour. These results are obtained with leave-one-out cross-validation. In
      addition, for 13 out of 18 patients, the AdaBoost classifier requires only one
      feature, while it requires 4 features for the remaining 5 patients. 

PMID- 25570979
TI  - Robust and low complexity algorithms for seizure detection.
AB  - This paper presents two low complexity and yet robust methods for automated
      seizure detection using a set of 2 intracranial Electroencephalogram (iEEG)
      recordings. Most current seizure detection methods suffer from high number of
      false alarms, even when designed to be subject-specific. In this study, the
      ratios of power between pairs of frequency bands are used as features to detect
      epileptic seizures. For comparison, these features are calculated from monopolar
      and bipolar iEEG recordings. Optimal thresholds are individually determined and
      used for each feature. Alarms are generated when the measure passes the
      threshold. The detector was applied to long-term continuous invasive recordings
      from 5 patients with refractory partial epilepsy, containing 54 seizures in 780
      hours. On average, the results revealed 88.9% sensitivity, a very low false
      detection rate of 0.041 per hour (h(-1)) and detection latency of 9.4 seconds. 

PMID- 25570980
TI  - Neonatal EEG audification for seizure detection.
AB  - Technologies for automated detection of neonatal seizures are gradually moving
      towards cot-side implementation. The aim of this paper is to present an
      alternative way to visualize the output of a neonatal seizure detection
      algorithm. For this purpose audified neonatal EEG is considered. The EEG is
      audified with the aid of the neonatal seizure detection algorithm which selects
      the representative channels for stereo audio image and controls the signal gain.
      A survey on the usefulness and accuracy of the presented audification method has
      been performed. The results of the audification method compare favourably to that
      of using amplitude integrated EEG for detection of neonatal seizures. 

PMID- 25570981
TI  - Gamma (30-80Hz) bicoherence distinguishes seizures in the human epileptic brain.
AB  - We have applied wavelet bicoherence (BIC) analysis to human iEEG data to
      characterize non-linear frequency interactions in the human epileptic brain.
      Bicoherence changes were most prominent in the gamma (30-80 Hz) frequency band,
      and allowed for the differentiation between seizure and non-seizure states in all
      patients studied (n=3). While gamma band BIC values increased during seizure
      activity, this trend was only observed in a select number of electrode(s) located
      on the implanted patient subdural grids. Several studies have suggested that fast
      frequencies may play a role in the process of seizure genesis. While the small
      patient numbers limit the significance of our study, our results highlight the
      bicoherence of the gamma frequency band (30-80 Hz) as an ictal identifier, and
      suggest an active role of this fast frequency during seizures. 

PMID- 25570983
TI  - The sternum as an electrical shield.
AB  - INTRODUCTION: The TASER((r)) conducted electrical weapon (CEW) delivers
      electrical pulses that can temporarily incapacitate subjects. We analyzed the
      distribution of TASER CEW currents in tissues posterior to the sternum to
      understand the likelihood of triggering cardiac arrhythmias. We also assessed the
      electrical 'shielding' effects of the sternum. METHODS AND RESULTS: Finite
      element modeling (FEM) was used to approximate the current density and electric
      field strength in tissues around the sternum. We analyzed 2 CEW dart deployment
      scenarios: (a) both darts over the anterior aspect of the sternum; and (b) a CEW
      dart anterior to the sternum and the other over the abdomen. In both scenarios,
      the sternum provided significant attenuation of CEW currents. Particularly, both
      FEMs predicted that the residual electrical current or charge from CEWs would be
      insufficient to cause either cardiac capture or induction of ventricular
      fibrillation at locations where cardiac tissue would reside relative to the
      posterior aspect of the sternum. CONCLUSION: The sternum offers significant
      'shielding' effect and protects the tissues posterior to it against effects of
      electrical current flow from anteriorly-placed CEW electrodes.

PMID- 25570982
TI  - A percutaneously implantable fetal pacemaker.
AB  - A miniaturized, self-contained pacemaker that could be implanted with a minimally
      invasive technique would dramatically improve the survival rate for fetuses that
      develop hydrops fetalis as a result of congenital heart block. We are currently
      validating a device that we developed to address this bradyarrhythmia.
      Preclinical studies in a fetal sheep model are underway to demonstrate that the
      device can be implanted via a minimally invasive approach, can mechanically
      withstand the harsh bodily environment, can induce effective contractions of the
      heart muscle with an adequate safety factor, and can successfully operate for the
      required device lifetime of three months using the previously-developed closed
      loop transcutaneous recharging system. 

PMID- 25570984
TI  - Transthoracic cardiac stimulation thresholds for short pulses.
AB  - INTRODUCTION: The most common cause of death due to electric shock is ventricular
      fibrillation (VF). This work reviews applicable results from the literature and
      provides an estimation model for the risk of VF with short-duration pulses.
      METHODS AND RESULTS: For 1 ms pulses, the predicted current and charge thresholds
      required for successful transthoracic cardiac stimulation were 1.12 A and 1.12
      mC, respectively. For pulses of 0.1 ms durations, the transthoracic current and
      charge thresholds predicted by the model are 10.9 A and 1.09 mC, respectively.
      CONCLUSION: In humans, the charge required for single-response cardiac capture
      using transthoracic electrodes and 0.1 ms pulses is at least 0.5 mC. The
      transthoracic charge required to trigger repetitive ventricular responses in
      humans is at least several times higher than that for single responses. Hence, in
      adult humans, the transthoracic charge threshold required to induce repetitive
      ventricular responses, tachycardia, or fibrillation, with 0.1 ms pulses is
      expected to be significantly greater than 1 mC.

PMID- 25570986
TI  - Application of Laser Doppler Vibrometery for human heart auscultation.
AB  - In this study the potential of a Laser Doppler Vibrometer (LDV) was tested as a
      non-contact sensor for the classification of heart sounds. Of the twenty
      participants recorded using the LDV, five presented with Aortic Stenosis (AS),
      three were healthy and twelve presented with other pathologies. The recorded
      heart sounds were denoised and segmented using a combination of the
      Electrocardiogram (ECG) data and the complexity of the signal. Frequency domain
      features were extracted from the segmented heart sound cycles and used to train a
      K-nearest neighbor classifier. Due to the small number of participants, the
      classifier could not be trained to differentiate between normal and abnormal
      participants, but could successfully distinguish between participants who
      presented with AS and those who did not. A sensitivity of 80 % and a specificity
      of 100 % were achieved a test dataset. 

PMID- 25570985
TI  - Neural network approach for non-invasive detection of hyperglycemia using
      electrocardiographic signals.
AB  - Hyperglycemia or high blood glucose (sugar) level is a common dangerous
      complication among patients with Type 1 diabetes mellitus (T1DM). Hyperglycemia
      can cause serious health problems if left untreated such as heart disease,
      stroke, vision and nerve problems. Based on the electrocardiographic (ECG)
      parameters, we have identified hyperglycemic and normoglycemic states in T1DM
      patients. In this study, a classification unit is introduced with the approach of
      feed forward multi-layer neural network to detect the presences of
      hyperglycemic/normoglycemic episodes using ECG parameters as inputs. A practical
      experiment using the real T1DM patients' data sets collected from Department of
      Health, Government of Western Australia is studied. Experimental results show
      that proposed ECG parameters contributed significantly to the good performance of
      hyperglycemia detections in term of sensitivity, specificity and geometric mean
      (70.59%, 65.38%, and 67.94%, respectively). From these results, it is proved that
      hyperglycemic events in T1DM can be detected non-invasively and effectively by
      using ECG signals and ANN approach. 

PMID- 25570987
TI  - Investigation of the biological effects of artificial perfusion using rat
      extracorporeal circulation model.
AB  - Extracorporeal circulation (ECC) is indispensable for cardiac surgery. Since
      difficulty in clinical research keeps the knowledge insufficient, it is desirable
      to have a miniature ECC system for small animals. We aimed to establish a
      miniature ECC system and apply the system to the rat for investigating
      biochemical changes. The ECC system consisted of a membranous oxygenator
      (polypropylene, 0.03 m(2)), tubing line (polyvinyl chloride) and roller pump.
      Priming volume of this system is only 15 ml. Rats were divided into the SHAM
      group and the ECC group. ECC pump flow was initiated and maintained at 70
      ml/kg/min. We measured the serum cytokine levels of tumor necrosis factor-a,
      interleukin (IL)-6, and IL-10, and biochemical markers (lactate dehydrogenase,
      aspartate aminotransferase and alanine aminotransferase) before, 60, and 120 min
      after the initiation of ECC. In addition, we measured the wet-to-dry weight (W/D)
      ratio of the left lung tissues. During ECC, blood pressure and Hb were maintained
      around 80 mmHg and 10g/dl, the serum cytokine levels and biochemical markers were
      significantly elevated in the ECC group compared with the SHAM group. The W/D
      ratio increased significantly more in the ECC group compared with that in the
      SHAM group. These data suggest that ECC promotes organ damages and systemic
      inflammatory response. This rat ECC model is considered to be equivalent to the
      already established human ECC and useful for studying the mechanism of
      pathophysiological changes during artificial perfusion. 

PMID- 25570988
TI  - USign--a security enhanced electronic consent model.
AB  - Electronic consent becomes increasingly popular in the healthcare sector given
      the many benefits it provides. However, security concerns, e.g., how to verify
      the identity of a person who is remotely accessing the electronic consent system
      in a secure and user-friendly manner, also arise along with the popularity of
      electronic consent. Unfortunately, existing electronic consent systems do not pay
      sufficient attention to those issues. They mainly rely on conventional password
      based authentication to verify the identity of an electronic consent user, which
      is far from being sufficient given that identity theft threat is real and
      significant in reality. In this paper, we present a security enhanced electronic
      consent model called USign. USign enhances the identity protection and
      authentication for electronic consent systems by leveraging handwritten
      signatures everyone is familiar with and mobile computing technologies that are
      becoming ubiquitous. We developed a prototype of USign and conducted preliminary
      evaluation on accuracy and usability of signature verification. Our experimental
      results show the feasibility of the proposed model. 

PMID- 25570989
TI  - Ontology-guided distortion control for robust-lossless database watermarking:
      application to inpatient hospital stay records.
AB  - In this paper, we propose a new semantic distortion control method for database
      watermarking. It is based on the identification of the semantic links that exist
      in-between attribute's values in tuples by means of an ontology. Such a database
      distortion control provides the capability for any watermarking scheme to avoid
      incoherent records and consequently ensures: i) the normal interpretation of
      watermarked data, i.e. introducing a watermark semantically imperceptible; ii)
      prevent the identification by an attacker of watermarked tuples. The solution we
      present herein successfully combines this semantic distortion control method with
      a robust lossless watermarking scheme. Experimental results conducted on a
      medical database of more than one half million of inpatient hospital stay records
      also show a non-negligible gain of performance in terms of robustness and
      database distortion. 

PMID- 25570990
TI  - Combination of watermarking and joint watermarking-decryption for reliability
      control and traceability of medical images.
AB  - In this paper, we propose a novel crypto-watermarking system for the purpose of
      verifying the reliability of images and tracing them, i.e. identifying the person
      at the origin of an illegal distribution. This system couples a common
      watermarking method, based on Quantization Index Modulation (QIM), and a joint
      watermarking-decryption (JWD) approach. At the emitter side, it allows the
      insertion of a watermark as a proof of reliability of the image before sending it
      encrypted; at the reception, another watermark, a proof of traceability, is
      embedded during the decryption process. The scheme we propose makes interoperate
      such a combination of watermarking approaches taking into account risks of
      interferences between embedded watermarks, allowing the access to both
      reliability and traceability proofs. Experimental results confirm the efficiency
      of our system, and demonstrate it can be used to identify the physician at the
      origin of a disclosure even if the image has been modified. 

PMID- 25570991
TI  - Evaluation of the performance of open-source RDBMS and triplestores for storing
      medical data over a web service.
AB  - An integral part of a system that manages medical data is the persistent storage
      engine. For almost twenty five years Relational Database Management
      Systems(RDBMS) were considered the obvious decision, yet today new technologies
      have emerged that require our attention as possible alternatives. Triplestores
      store information in terms of RDF triples without necessarily binding to a
      specific predefined structural model. In this paper we present an attempt to
      compare the performance of Apache JENA-Fuseki and the Virtuoso Universal Server 6
      triplestores with that of MySQL 5.6 RDBMS for storing and retrieving medical
      information that it is communicated as RDF/XML ontology instances over a RESTful
      web service. The results show that the performance, calculated as average time of
      storing and retrieving instances, is significantly better using Virtuoso Server
      while MySQL performed better than Fuseki. 

PMID- 25570992
TI  - A novel trust evaluation method for Ubiquitous Healthcare based on cloud
      computational theory.
AB  - The notion of trust is considered to be the cornerstone on patient-psychiatrist
      relationship. Thus, a trustfully background is fundamental requirement for
      provision of effective Ubiquitous Healthcare (UH) service. In this paper, the
      issue of Trust Evaluation of UH Providers when register UH environment is
      addressed. For that purpose a novel trust evaluation method is proposed, based on
      cloud theory, exploiting User Profile attributes. This theory mimics human
      thinking, regarding trust evaluation and captures fuzziness and randomness of
      this uncertain reasoning. Two case studies are investigated through simulation in
      MATLAB software, in order to verify the effectiveness of this novel method. 

PMID- 25570993
TI  - Facilitating medical information search using Google Glass connected to a content
      based medical image retrieval system.
AB  - Wearable computing devices are starting to change the way users interact with
      computers and the Internet. Among them, Google Glass includes a small screen
      located in front of the right eye, a camera filming in front of the user and a
      small computing unit. Google Glass has the advantage to provide online services
      while allowing the user to perform tasks with his/her hands. These augmented
      glasses uncover many useful applications, also in the medical domain. For
      example, Google Glass can easily provide video conference between medical doctors
      to discuss a live case. Using these glasses can also facilitate medical
      information search by allowing the access of a large amount of annotated medical
      cases during a consultation in a non-disruptive fashion for medical staff. In
      this paper, we developed a Google Glass application able to take a photo and send
      it to a medical image retrieval system along with keywords in order to retrieve
      similar cases. As a preliminary assessment of the usability of the application,
      we tested the application under three conditions (images of the skin; printed CT
      scans and MRI images; and CT and MRI images acquired directly from an LCD screen)
      to explore whether using Google Glass affects the accuracy of the results
      returned by the medical image retrieval system. The preliminary results show that
      despite minor problems due to the relative stability of the Google Glass, images
      can be sent to and processed by the medical image retrieval system and similar
      images are returned to the user, potentially helping in the decision making
      process. 

PMID- 25570994
TI  - A novel web-based depth video rewind approach toward fall preventive
      interventions in hospitals.
AB  - The purpose of this study was to implement a web based application to provide the
      ability to rewind and review depth videos captured in hospital rooms to
      investigate the event chains that led to patient's fall at a specific time. In
      this research, Kinect depth images are being used to capture shadow-like images
      of the patient and their room to resolve concerns about patients' privacy. As a
      result of our previous research, a fall detection system has been developed and
      installed in hospital rooms, and fall alarms are generated if any falls are
      detected by the system. Then nurses will go through the stored depth videos to
      investigate for possible injury as well as the reasons and events that may have
      caused the patient's fall to prevent future occurrences. This paper proposes a
      novel web application to ease the process of search and reviewing the videos by
      means of new visualization techniques to highlight video frames that contain
      potential risk of fall based on our previous research. 

PMID- 25570995
TI  - A gait analysis method based on a depth camera for fall prevention.
AB  - This paper proposes a markerless system whose purpose is to help preventing falls
      of elderly people at home. To track human movements, the Microsoft Kinect camera
      is used which allows to acquire at the same time a RGB image and a depth image.
      Several articles show that the analysis of some gait parameters could allow fall
      risk assessment. We developed a system which extracts three gait parameters (the
      length and the duration of steps and the speed of the gait) by tracking the
      center of mass of the person. To check the validity of our system, the accuracy
      of the gait parameters obtained with the camera is evaluated. In an experiment,
      eleven subjects walked on an actimetric carpet, perpendicularly to the camera
      which filmed the scene. The three gait parameters obtained by the carpet are
      compared with those of the camera. In this study, four situations were tested to
      evaluate the robustness of our model. The subjects walked normally, making small
      steps, wearing a skirt and in front of the camera. The results showed that the
      system is accurate when there is one camera fixed perpendicularly. Thus we
      believe that the presented method is accurate enough to be used in real fall
      prevention applications. 

PMID- 25570996
TI  - Proposal of a Kinect(TM)-based system for gait assessment and rehabilitation in
      Parkinson's disease.
AB  - It has been proved that audio and visual cueing can improve the motor performance
      of Parkinson's disease patients. Specially, gait can benefit from repetitive
      sessions of exercises using cues. Nevertheless, these effects are not permanent
      and fade away with time, in that sense, home game systems can be an excellent
      platform for patients to perform daily exercises, as well as to coach and guide
      them in a smarter way. Within this work a method to track the walking movement is
      proposed based on the signals coming from the Kinect sensor of Microsoft. At the
      same time, different setups have been tested in order to study the feasibility of
      using this sensor to build a game platform for gait rehabilitation for
      Parkinson's disease patients. 

PMID- 25570997
TI  - A theoretical study on the placement of microphone arrays for improving the
      localization accuracy of a fall.
AB  - Falling is a common health problem for elderly. To address the problem, we are
      currently developing an acoustic fall detection system, FADE, which automatically
      detects a fall and reports to the caregiver. Of great importance of the fall
      detection system is a low false alarm rate that can be achieved by knowing where
      the acoustic signal comes from. The previous work showed the sound source
      localization can be determined by using an 8-microphone circular array, but the
      accuracy varies when placing the array at different positions. To further improve
      the localization accuracy, a second array can be added. In this paper we
      investigate the variations of localization accuracy of a fall signal when one or
      two arrays are placed at different positions in a room. The accuracy is evaluated
      by the Cramer-Rao Lower Bound (CRLB). The CRLB aids the determination of the best
      theoretical placement of one or two arrays in a room for locating the sound
      source. 

PMID- 25570998
TI  - A comparison of cross-sectional and prospective algorithms for falls risk
      assessment.
AB  - Falls are the most common cause of injury and hospitalization and one of the
      principal causes of death and disability in older adults worldwide. Accurate
      identification of patients at risk of falls could lead to timely medical
      intervention, reducing the incidence of falls related injuries along with
      associated costs. The current best practice for studies of falls and falls risk
      recommends the use of prospective follow-up data. However, the majority of
      studies reporting sensor based methods for assessment of falls risk employ cross
      sectional falls data (falls history). The purpose of this study was to compare
      the performance of sensor based falls risk assessment algorithms derived from
      cross-sectional (N=909) and prospective (N=259) datasets in terms of false
      positive rate. The utility of any classification algorithm is clearly limited by
      a high false positive rate. An estimate of the false positive rate for both cross
      sectional and prospective algorithms was determined using an inertial sensor data
      set of 611 TUG tests from 55 healthy control subjects, with no history of falls.
      We aimed to determine which falls risk assessment algorithm is more effective at
      classifying falls risk in healthy control subjects. The cross-sectional algorithm
      correctly classified 94.11% of tests, while the prospective algorithm, correctly
      classified 79.38% of tests. Results suggest that sensor based falls risk
      assessment algorithms generated using cross-sectional falls data, may be more
      effective than those generated using prospective data in classifying healthy
      controls and reducing associated false positives. 

PMID- 25570999
TI  - Validation of an accelerometer-based fall prediction model.
AB  - Falls are a common and serious problem faced by older populations. There is a
      growing interest in estimating the risk of falling for older people using body
      worn sensors and simple movement tasks, allowing appropriate fall prevention
      programs to be administered in a timely manner to the high risk population. This
      study investigated the capability and validity of using a waist-mounted triaxial
      accelerometer (TA) and a directed routine (DR) that includes three movement tasks
      to discriminate between fallers and non-fallers and between multiple fallers and
      non-multiple fallers. Data were collected from 98 subjects who were stratified
      into two separate groups, one for model training and the other for model
      validation. Logistic regression models were constructed using the TA features
      from the entire DR and from each single DR task, and were validated using unseen
      data. The best models were obtained using features from the alternate step test
      to classify between fallers and non-fallers with kappa = 0.34-0.41, sensitivity =
      68%-71% and specificity = 63%-73%. However, the overall validation performances
      were poor. The study emphasizes the importance of independent validation in fall
      prediction studies. 

PMID- 25571000
TI  - Ionic channel changes in glaucomatous retinal ganglion cells: multicompartment
      modeling.
AB  - This research takes a step towards discovering underlying ionic channel changes
      in the glaucomatous ganglion cells. Glaucoma is characterized by a gradual death
      of retinal ganglion cells. In this paper, we propose a hypothesis that the ionic
      channel concentrations change during the progression of glaucoma. We use computer
      simulation of a multi-compartment morphologically correct model of a mouse
      retinal ganglion cell to verify our hypothesis. Using published experimental
      data, we alter the morphology of healthy ganglion cells to replicate glaucomatous
      cells. Our results suggest that in glaucomatous cell, the sodium channel
      concentration decreases in the soma by 30% and by 60% in the dendrites, calcium
      channel concentration decreases by 10% in all compartments, and leak channel
      concentration increases by 40% in the soma and by 100% in the dendrites. 

PMID- 25571001
TI  - Laguerre-Volterra model and architecture for MIMO system identification and
      output prediction.
AB  - A generalized mathematical model is proposed for behaviors prediction of
      biological causal systems with multiple inputs and multiple outputs (MIMO). The
      system properties are represented by a set of model parameters, which can be
      derived with random input stimuli probing it. The system calculates predicted
      outputs based on the estimated parameters and its novel inputs. An efficient
      hardware architecture is established for this mathematical model and its
      circuitry has been implemented using the field-programmable gate arrays (FPGAs).
      This architecture is scalable and its functionality has been validated by using
      experimental data gathered from real-world measurement. 

PMID- 25571002
TI  - A mixed effects model framework for the assessment of nonlinear interactions in
      event-related potentials (ERPs) elicited by identical successive stimuli.
AB  - The recording of brain event-related potentials (ERPs) is a widely used technique
      to investigate the neural basis of sensory perception and cognitive processing in
      humans. A commonly used assumption, when dealing with potentially overlapping
      ERPs elicited by successive stimuli with interstimulus interval (ISI) smaller
      than the latency of the ERPs, is that their interaction is linear. These overlaps
      are usually dealt by using averaged waveforms, mostly to enhance the signal-to
      noise ratio (SNR) and performing algebraic waveform subtractions. In this paper,
      we examine the hypothesis of linear interactions by providing a statistical
      framework that examines the presence of nonlinear additive effects between
      overlapping ERPs elicited by successive stimuli with short ISIs. The statistical
      analysis is designed for single trial rather than averaged waveforms. The results
      suggest that there are no nonlinear additive effects due to the time overlap per
      se but that, for the range of ISIs examined, the second ERP is modulated by the
      presence of the first stimulus irrespective of whether there is time overlap or
      not. In other words, two ERPs that overlap in time can still be written as an
      addition of two ERPs, with the second ERP being different to the first. The
      modulation effect on the second ERP by the first stimulus varies for different
      ISIs. 

PMID- 25571003
TI  - Towards robust HD EMG pattern recognition: reducing electrode displacement effect
      using structural similarity.
AB  - Even small changes of electrode recording sites after training a classifier
      heavily influence robustness and usability of traditional pattern recognition
      based myoelectric control schemes. This effect occurs during donning and doffing
      of the prosthesis or when changing the arm position and generally leads to a
      significant decrease of classification accuracy. On the other hand, image
      representations taken from high density electromyographic (EMG) signals offer
      high spatial resolution and only seem to change slightly during electrode shift,
      preserving most structural information. In this paper, we present a simple one
      against-one nearest neighbor classifier based on the Structural Similarity Index
      (SSIM). SSIM quantifies visual similarity of two images based on decomposition
      into three components: luminance, contrast and structure. Our experimental
      results indicate that an SSIM-based classifier can outperform an LDA-based
      classifier using structural information taken from high density EMG signals
      during simulated electrode shift. 

PMID- 25571004
TI  - Brain source localization in the presence of leadfield perturbations.
AB  - This paper studies the performance of the recently developed G-MUSIC algorithm as
      applied to the problem of brain source localization. G-MUSIC is a form of
      weighted MUSIC that performs better in scenarios where only limited sample
      support is available. Two transfer function based calibration algorithms are also
      developed to estimate the location of neural activity in the brain accurately
      when the measured leadfield is perturbed. The localization performance of G-MUSIC
      is compared to traditional MUSIC and quantified in terms of the localization
      error. Simulations suggest that G-MUSIC can offer significantly improved
      localization accuracy over conventional MUSIC. 

PMID- 25571005
TI  - Adaptation of five indirect insulin sensitivity evaluation methods to three
      populations: metabolic syndrome, athletic and normal subjects.
AB  - Insulin sensitivity is determined using direct or indirect methods. Indirect
      methods are less invasive than direct methods, but have lower accuracy. The
      accuracy is set through the Spearman's rank correlation coefficient between the
      indirect method and a direct method. Since the set of parameters of each indirect
      method has been set empirically, different values of insulin sensitivity have
      been reported when they are applied on different populations. In this paper, five
      indirect methods (Avignon, HOMA-IR, QUICKI, Raynaud, and Matsuda) used to
      determine insulin sensitivity were adapted to three different populations:
      athletics, metabolic syndrome and normal subjects. The parameters of each method
      were varied in a range of values until the optimal value that gives the best
      correlation coefficient with a gold standard was obtained. Results show that the
      adaptation procedure led to an improved correlation coefficient. Additionally,
      the method of Matsuda was the most accurate, followed by the method of Avignon.
      We have confirmed that each indirect method needs a different set of parameters
      when it is applied to a specific population in order to obtain an accurate value
      of insulin sensitivity. 

PMID- 25571007
TI  - Using Lorenz plot and Cardiac Sympathetic Index of heart rate variability for
      detecting seizures for patients with epilepsy.
AB  - Tachycardia is often seen during epileptic seizures, but it also occurs during
      physical exercise. In order to assess whether focal epileptic seizures can be
      detected by short term moving window Heart Rate Variability (HRV) analysis, we
      modified the geometric HRV method, Lorenz plot, to consist of only 30, 50 or 100
      R-R intervals per analyzed window. From each window we calculated the
      longitudinal (L) and transverse (T) variability of Lorenz plot to retrieve the
      Cardiac Sympathetic Index (CSI) as (L/T) and "Modified CSI" (described in
      methods), and compared the maximum during the patient's epileptic seizures with
      that during the patient's own exercise and non-seizure sessions as control. All
      five analyzed patients had complex partial seizures (CPS) originating in the
      temporal lobe (11 seizures) during their 1-5 days long term video-EEG monitoring.
      All CPS with electroencephalographic correlation were selected for the HRV
      analysis. The CSI and Modified CSI were correspondently calculated after each
      heart beat depicting the prior 30, 50 and 100 R-R intervals at the time. CSI (30,
      50 and 100) and Modified CSI (100) showed a higher maximum peak during seizures
      than exercise/non-seizure (121-296%) for 4 of the 5 patients within 4 seconds
      before till 60 seconds after seizure onset time even though exercise maximum HR
      exceeded that of the seizures. The results indicate a detectable, sudden and
      inordinate shift towards sympathetic overdrive in the sympathovagal balance of
      the autonomic nervous system just around seizure-onset for certain patients. This
      new modified moving window Lorenz plot method seems promising way of constructing
      a portable ECG-based epilepsy alarm for certain patients with epilepsy who needs
      aid during seizure. 

PMID- 25571006
TI  - Model of human breathing reflected signal received by PN-UWB radar.
AB  - Human detection is an integral component of civilian and military rescue
      operations, military surveillance and combat operations. Human detection can be
      achieved through monitoring of vital signs. In this article, a mathematical model
      of human breathing reflected signal received in PN-UWB radar is proposed. Unlike
      earlier published works, both chest and abdomen movements are considered for
      modeling the radar return signal along with the contributions of fundamental
      breathing frequency and its harmonics. Analyses of recorded reflected signals
      from three subjects in different postures and at different ranges from the radar
      indicate that ratios of the amplitudes of the harmonics contain information about
      posture and posture change. 

PMID- 25571008
TI  - Estimating blood pressure using Windkessel model on Photoplethysmogram.
AB  - Simple and non-invasive methods to estimate vital signs are very important for
      preventive healthcare. In this paper, we present a methodology to estimate Blood
      Pressure (BP) using Photoplethysmography (PPG). Instead of directly relating
      systolic and diastolic BP values with PPG features, our proposed methodology
      initially maps PPG features with some person specific intermediate latent
      parameters and later derives BP values from them. The 2-Element Windkessel model
      has been considered in the current context to estimate total peripheral
      resistance and arterial compliance of a person using PPG features, followed by
      linear regression for simulating arterial blood pressure. Experimental results,
      performed on a standard hospital dataset yielded absolute errors of 0.78+/-13.1
      mmHg and 0.59 +/- 10.23 mmHg for systolic and diastolic BP values respectively.
      Results also indicate that the methodology is more robust than the standard
      methodologies that directly estimate BP values from PPG signal. 

PMID- 25571009
TI  - Low-cost EEG-based sleep detection.
AB  - A real-time stage 1 sleep detection system using a low-cost single dry-sensor EEG
      headset is described. This device issues an auditory warning at the onset of
      stage 1 sleep using the "NeuroSky Mindset," an inexpensive commercial
      entertainment-based headset. The EEG signal is filtered into low/high alpha and
      low/high beta frequency bands which are analyzed to indicate the onset of sleep.
      Preliminary results indicate an 81% effective rate of detecting sleep with all
      failures being false positives of sleep onset. This device was able to predict
      and respond to the onset of drowsiness preceding stage 1 sleep allowing for
      earlier warnings with the result of fewer sleep-related accidents. 

PMID- 25571010
TI  - Analysis of EEG to quantify depth of anesthesia using Hidden Markov Model.
AB  - Real-time quantification of the patient's consciousness level during anesthesia
      is an important issue to avoid intraoperative awareness and post-operative side
      effects. A depth-of-anesthesia (DoA) monitoring method called Bispectral Index
      (BIS) is generally used for this purpose. However, BIS is known to be inaccurate
      at the transitory state, and also shows a critical time delay in quantifying the
      patient's consciousness level. This paper introduces a novel method to reduce the
      response time in the quantification process. This thesis develops a new index
      called HDoA by analyzing EEG using Hidden Markov Model. The proposed approach is
      composed by two steps, training and testing. In the training step, two HMM,
      awakened and anesthetized model are learned based on each training set. In the
      testing step, by evaluating the probability of producing the testing EEG from two
      models respectively, the index HDoA is derived. Since the evaluation of DoA using
      HMM is training based method, it have better performance with more training
      process. Experiments show that HDoA has a high correlation with BIS at a steady
      state, and outperforms BIS in two ways: (1) shorter delay time in transition
      state, and (2) higher Fisher Score. The validity of HDoA has been tested by 8
      real clinical data. 

PMID- 25571011
TI  - Sleep stage classification with cross frequency coupling.
AB  - Sleep is a key requirement for an individual's health, though currently the
      options to study sleep rely largely on manual visual classification methods. In
      this paper we propose a new scheme for automated offline classification based
      upon cross-frequency-coupling (CFC) and compare it to the traditional band power
      estimation and the more recent preferential frequency band information
      estimation. All three approaches allowed sleep stage classification and provided
      whole-night visualization of sleep stages. Surprisingly, the simple average power
      in band classification achieved better overall performance than either the
      preferential frequency band information estimation or the CFC approach. However,
      combined classification with both average power and CFC features showed improved
      classification over either approach used singly. 

PMID- 25571012
TI  - Short time effect of Delta oscillation under microcurrent transcutaneous
      electrical nerve stimulation at ST36.
AB  - This paper was to study the short time effect of Delta brain oscillation under
      microcurrent transcutaneous electrical nerve stimulation (MTENS) at ST36
      (Zusanli). The 64-channal electroencephalograph (EEG) signals from 12 healthy
      volunteers were recorded including baseline stage, during stimulation and after
      stimulation. Autoregressive (AR) Burg method was used to estimate the power
      spectrum. Then power variation rate (PVR) was calculated to quantify the effects
      compared with the baseline in Delta band. The results showed that MTENS at ST36
      on right side led to increased Delta band power in left frontal. 

PMID- 25571013
TI  - Effects of single cycle binaural beat duration on auditory evoked potentials.
AB  - Binaural beat (BB) illusions are experienced as continuous central pulsations
      when two sounds with slightly different frequencies are delivered to each ear. It
      has been shown that steady-state auditory evoked potentials (AEPs) to BBs can be
      captured and investigated. The authors recently developed a new method of evoking
      transient AEPs to binaural beats using frequency modulated stimuli. This
      methodology was able to create single BBs in predetermined intervals with varying
      carrier frequencies. This study examines the effects of the BB duration and the
      frequency modulating component of the stimulus on the binaural beats and their
      evoked potentials. Normal hearing subjects were tested with a set of four
      durations (25, 50, 100, and 200 ms) with two stimulation configurations, binaural
      dichotic (binaural beats) and diotic (frequency modulation). The results obtained
      from the study showed that out of the given durations, the 100 ms beat, was
      capable of evoking the largest amplitude responses. The frequency modulation
      effect showed a decrease in peak amplitudes with increasing beat duration until
      their complete disappearance at 200 ms. Even though, at 200 ms, the frequency
      modulation effects were not present, the binaural beats were still perceived and
      captured as evoked potentials. 

PMID- 25571014
TI  - ERP and Adaptive Autoregressive identification with spectral power decomposition
      to study rapid auditory processing in infants.
AB  - The ability to process rapidly-occurring auditory stimuli plays an important role
      in the mechanisms of language acquisition. For this reason, the research
      community has begun to investigate infant auditory processing, particularly using
      the Event Related Potentials (ERP) technique. In this paper we approach this
      issue by means of time domain and time-frequency domain analysis. For the latter,
      we propose the use of Adaptive Autoregressive (AAR) identification with spectral
      power decomposition. Results show EEG delta-theta oscillation enhancement related
      to the processing of acoustic frequency and duration changes, suggesting that, as
      expected, power modulation encodes rapid auditory processing (RAP) in infants and
      that the time-frequency analysis method proposed is able to identify this
      modulation. 

PMID- 25571015
TI  - Changes in music tempo entrain movement related brain activity.
AB  - The neural mechanisms of music listening and appreciation are not yet completely
      understood. Based on the apparent relationship between the beats per minute
      (tempo) of music and the desire to move (for example feet tapping) induced while
      listening to that music it is hypothesised that musical tempo may evoke movement
      related activity in the brain. Participants are instructed to listen, without
      moving, to a large range of musical pieces spanning a range of styles and tempos
      during an electroencephalogram (EEG) experiment. Event-related desynchronisation
      (ERD) in the EEG is observed to correlate significantly with the variance of the
      tempo of the musical stimuli. This suggests that the dynamics of the beat of the
      music may induce movement related brain activity in the motor cortex.
      Furthermore, significant correlations are observed between EEG activity in the
      alpha band over the motor cortex and the bandpower of the music in the same
      frequency band over time. This relationship is observed to correlate with the
      strength of the ERD, suggesting entrainment of motor cortical activity relates to
      increased ERD strength. 

PMID- 25571016
TI  - Single trial detection of hand poses in human ECoG using CSP based feature
      extraction.
AB  - Decoding brain activity of corresponding highlevel tasks may lead to an
      independent and intuitively controlled Brain-Computer Interface (BCI). Most of
      today's BCI research focuses on analyzing the electroencephalogram (EEG) which
      provides only limited spatial and temporal resolution. Derived
      electrocorticographic (ECoG) signals allow the investigation of spatially highly
      focused task-related activation within the high-gamma frequency band, making the
      discrimination of individual finger movements or complex grasping tasks possible.
      Common spatial patterns (CSP) are commonly used for BCI systems and provide a
      powerful tool for feature optimization and dimensionality reduction. This work
      focused on the discrimination of (i) three complex hand movements, as well as
      (ii) hand movement and idle state. Two subjects S1 and S2 performed single
      'open', 'peace' and 'fist' hand poses in multiple trials. Signals in the high
      gamma frequency range between 100 and 500 Hz were spatially filtered based on a
      CSP algorithm for (i) and (ii). Additionally, a manual feature selection approach
      was tested for (i). A multi-class linear discriminant analysis (LDA) showed for
      (i) an error rate of 13.89 % / 7.22 % and 18.42 % / 1.17 % for S1 and S2 using
      manually / CSP selected features, where for (ii) a two class LDA lead to a
      classification error of 13.39 % and 2.33 % for S1 and S2, respectively. 

PMID- 25571017
TI  - Characterization of HFOs in short and long duration discharges recorded from in
      vivo MeCP2-deficient mice.
AB  - Mutations in the X-linked gene encoding methyl CpG-binding protein 2 (MeCP2) have
      been linked to a neurodevelopmental disorder known as Rett syndrome. The disorder
      is associated with a number of symptoms, of which epileptic seizures are common.
      In this study we examined the presence of high frequency oscillations (HFOs) and
      their interactions with low frequency oscillations (LFOs) during epileptiform
      like discharges using intracranial electroencephalogram (iEEG) recordings from
      male and female Mecp2-deficient mice. The study compared differences in mean HFO
      power levels normalized to baseline along with LFO-HFO modulation observed in
      short and long duration discharges. Short duration discharges, common to both
      male and female Mecp2-deficient mice, showed a decrease in mean HFO power levels
      compared to baseline levels. During the short duration discharges the theta (7-9
      Hz) LFOs were found to modulate fast ripple (350-500 Hz) HFOs predominantly in
      the female Mecp2-deficient mice. Long duration discharges, predominantly observed
      in male Mecp2-deficient mice, were found to have elevated mean power levels in
      the ripple (80-200 Hz) and fast ripple (350-500 Hz) frequency ranges when
      compared to baseline. During the long duration discharges a lower frequency range
      theta LFO (4-6 Hz) modulated both the ripple (80-200 Hz) and fast ripple (350-500
      Hz) HFOs. These findings suggest that the long duration discharges observed in
      male Mecp2-deficient mice share biomarkers indicative of seizure-like activity. 

PMID- 25571018
TI  - Spectral envelope and periodic component in classification trees for pathological
      voice diagnostic.
AB  - This work investigates the effectiveness of features from the spectral envelope
      such as the frequency and bandwidth of the first peak obtained from a 30(th)
      order Linear Predictive Coefficients (LPC) to identify pathological voices. Other
      spectral features are also investigated and tested to improve the recognition
      rate. The value of the Relative Power of the Periodic Component is combined with
      spectral features, to diagnose pathological voices. Healthy voices and five vocal
      folds pathologies are tested. Decision Tree classifiers are used to evaluate
      which features have pathological voice information. Based on those results a
      simple Decision Tree was implemented and 94% of all the subjects in the database
      are correctly diagnosed. 

PMID- 25571019
TI  - An acoustic method to automatically detect pressurized metered dose inhaler
      actuations.
AB  - Chronic respiratory diseases such as asthma and chronic obstructive pulmonary
      disease (COPD) affect over 400 million people and are incurable. The pressurized
      metered dose inhaler (pMDI) has been the most popular inhaler device in inhaled
      therapy in recent times. However the pMDIs require good coordination between
      inhaling and actuating the inhaler to deliver the aerosolized drug most
      effectively. Poor coordination can greatly reduce the amount of drug delivered to
      a patient and therefore reducing the control of respiratory disease symptoms.
      Acoustic methods have been recently employed to monitor inhaler technique quite
      effectively. This study employs a noninvasive acoustic method to detect actuation
      sounds in a portable monitoring device. A total of 158 actuation sounds were
      obtained from a group of healthy subjects (n=5) and subjects suffering from
      respiratory diseases (n=15). The developed algorithm generated an overall
      accuracy of 99.7% demonstrating that this method may have clinical potential to
      monitor pMDI actuation coordination. The informative feedback from this method
      may also be employed in clinical training to highlight patient actuation
      technique. 

PMID- 25571020
TI  - Acceleration trajectory analysis in remote gait monitoring.
AB  - The study demonstrates part of an ambient assisted living system developed for
      the remote care of the elderly. Described methods and experiments involve
      acceleration-based trajectories analysis that yields a feature vector to be
      subjected to an expert system able to create an individual patient's model by
      learning high-level features of her/his motion. At this stage we have implemented
      a footstep detector that permits each foot movement to be analyzed separately and
      described in terms of predefined features. By mounting the sensors at five
      various locations on the subjects body, we have indicated areas that feature a
      high sensitivity to the measurement of abnormal step incidents. Our experiments
      demonstrate also features able to distinguish abnormal patient motion. 

PMID- 25571021
TI  - Physiology-based diagnosis algorithm for arteriovenous fistula stenosis
      detection.
AB  - In this paper, a diagnosis algorithm for arteriovenous fistula (AVF) stenosis is
      developed based on auscultatory features, signal processing, and machine
      learning. The AVF sound signals are recorded by electronic stethoscopes at pre
      defined positions before and after percutaneous transluminal angioplasty (PTA)
      treatment. Several new signal features of stenosis are identified and quantified,
      and the physiological explanations for these features are provided. Utilizing
      support vector machine method, an average of 90% two-fold cross-validation hit
      rate can be obtained, with angiography as the gold standard. This offers a non
      invasive easy-to-use diagnostic method for medical staff or even patients
      themselves for early detection of AVF stenosis. 

PMID- 25571022
TI  - Self-adaptive fall-detection apparatus embedded in glasses.
AB  - Fall injury is already a major problem in elderly health care. This work develops
      a self-adaptive fall-detection apparatus which is embedded in glasses for users
      easily to put on. The proposed system adopts a 9-axis sensing module of a
      triaxial magnetometer, accelerometer and gyroscope. First, the magnetometer is to
      filter out some normal events like head rotating, based on variations of rotation
      angles which are modeled by the Gaussian mixture model. Second, the sensed
      signals from a triaxial accelerometer are computed to obtain differential
      acceleration values at three directions, which are integrated and then compared
      with a threshold. Here, the threshold is determined by the Gaussian mixture model
      and optimized thresholding technique. Our system can update an adequate threshold
      on the fly. Third, when a fall occurs, its direction is identified using an
      accelerometer and a gyroscope. The experimental results reveal that the proposed
      system achieves accuracy rate of 92.1%, a specificity of 98.7%, and a sensitivity
      of 81.7%. As compared to the conventional fall-detection systems, the proposed
      system not only shows fairly good performance but also provides convenient,
      comfortable and non-intrusive wearing. Therefore, the system proposed herein can
      be widely spread in various head-mounted devices for health care applications. 

PMID- 25571023
TI  - Multiscale feature based analysis of surface EMG signals under fatigue and non
      fatigue conditions.
AB  - In this work, an attempt has been made to differentiate sEMG signals under muscle
      fatigue and non-fatigue conditions using multiscale features. Signals are
      recorded from biceps brachii muscle of 50 normal adults during repetitive dynamic
      contractions. After prescribed preprocessing, each signal is divided into six
      segments out of which first and last segments are considered in this analysis.
      Multiscale RMS (MSRMS) and Multiscale Permutation Entropy (MSPE) are computed for
      each subject in the time scales ranging from 1 to 50. The median values of the
      MSRMS and MSPE are calculated for further analysis. The results show an increase
      in amplitude for sEMG signals under fatigue condition. MSRMS values are found to
      be significantly higher in fatigue. An approximately constant difference in MSRMS
      value between fatigue and non-fatigue condition is observed over the entire time
      scale with a negative slope. Further, the median of MSRMS values for each subject
      is able to distinguish fatigue and non-fatigue conditions. Similar analysis on
      MSPE showed significant difference between fatigue and non-fatigue cases and
      lower values of MSPE is observed in fatigue. It is also observed that the median
      value of MSRMS and MSPE are able to distinguish these conditions. t-test for
      MSRMS, MSPE and their median value show high statistical significance. It appears
      that this method of analysis can be used for clinical evaluation of muscles. 

PMID- 25571024
TI  - Using Empirical Mode Decomposition with Spatio-Temporal dynamics to classify
      single-trial Motor Imagery in BCI.
AB  - This paper introduces a new signal processing method called Spatio-Temporal
      Multivariate Empirical Mode Decomposition (ST-MEMD). It is a new variation of
      Empirical Mode Decomposition (EMD) that takes spatial and temporal information
      into account simultaneously rather than processing each signal source in
      isolation. The original and new methods were tested on single-trial
      electroencephalogram data with a two-class problem, in this case data using the
      Motor Imagery paradigm in brain-computer interfacing. However, whilst ST-MEMD
      retained the increase in sensitivity and specificity from adding spatial data,
      the new temporal data made no meaningful difference in terms of performance. 

PMID- 25571025
TI  - Local self similar descriptors: comparison and application to gastroenterology
      images.
AB  - Local descriptors coupled with robust methods for learning visual dictionaries
      have been a pivotal tool in computer vision. Although the identification of
      similar patterns is commonly conducted on some stage of the bag-of-words
      framework, a prior assessment of spatial local similarities can be indicative of
      specific objects, and thus improved recognition rates. In this work we delve a
      function of similarity for enhancing the discriminative power of local
      constrained SIFT descriptors. Motivated by gastrointestinal images where
      diagnosis through endoscopy plays a decisive role in cancer detection and
      resulting prognosis, visual cues in these early stages are slim and of difficult
      perception. In order to capture these patterns we propose a self-similarity
      approach (based on a neighbourhood analysis of SIFT descriptors) to assess local
      variances through a weight function. Based on extensive simulations our approach
      achieved a performance of 88%: 3% higher than the standard SIFT, 10% higher than
      Haar wavelet and 13% higher than LBPs. 

PMID- 25571026
TI  - The influence of the analysis technique on estimating liver iron overload using
      magnetic resonance imaging T2* quantification.
AB  - Iron toxicity is the major cause of tissue damage in patients with iron overload.
      Iron deposits mainly in the liver, where its concentration closely correlates
      with whole body iron overload. Different techniques have been proposed for
      estimating iron content, with liver biopsy being the gold standard despite its
      invasiveness and influence by sampling error. Recently, magnetic resonance
      imaging (MRI) has been established as an effective technique for evaluating iron
      overload by measuring T2(*) in the liver. However, various factors associated
      with the adopted analysis technique, mainly the exponential fitting model and
      signal averaging method, affect the resulting measurements. In this study, we
      evaluate the influences of these factors on T2(*) measurement in numerical
      phantom, calibrated phantoms, and nine patients with different degrees of iron
      overload. The results show different performances among the fitting models and
      signal averaging methods, which are affected by SNR, image quality and signal
      homogeneity inside the selected ROI for analysis. 

PMID- 25571027
TI  - Automatic image analysis of multicellular apoptosis process.
AB  - Apoptotic programmed cell death (PCD) is a common and fundamental aspect of
      developmental maturation. Image processing techniques have been developed to
      detect apoptosis at the single-cell level in a single still image, while an
      efficient algorithm to automatically analyze the temporal progression of
      apoptosis in a large population of cells is unavailable. In this work, we have
      developed an ImageJ-based program that can quantitatively analyze time-lapse
      microscopy movies of live tissues undergoing apoptosis with a fluorescent
      cellular marker, and subsequently extract the temporospatial pattern of
      multicellular response. The protocol is applied to characterize apoptosis of
      Drosophila wing epithelium cells at eclosion. Using natural anatomic structures
      as reference, we identify dynamic patterns in the progression of apoptosis within
      the wing tissue, which not only confirms the previously observed collective cell
      behavior from a quantitative perspective for the first time, but also reveals a
      plausible role played by the anatomic structures in Drosophila apoptosis. 

PMID- 25571028
TI  - Automated surgical step recognition in normalized cataract surgery videos.
AB  - Huge amounts of surgical data are recorded during video-monitored surgery.
      Content-based video retrieval systems intent to reuse those data for computer
      aided surgery. In this paper, we focus on real-time recognition of cataract
      surgery steps: the goal is to retrieve from a database surgery videos that were
      recorded during the same surgery step. The proposed system relies on motion
      features for video characterization. Motion features are usually impacted by eye
      motion or zoom level variations, which are not necessarily relevant for surgery
      step recognition. Those problems certainly limit the performance of the retrieval
      system. We therefore propose to refine motion feature extraction by applying pre
      processing steps based on a novel pupil center and scale tracking method. Those
      pre-processing steps are evaluated for two different motion features. In this
      paper, a similarity measure adapted from Piciarelli's video surveillance system
      is evaluated for the first time in a surgery dataset. This similarity measure
      provides good results and for both motion features, the proposed preprocessing
      steps improved the retrieval performance of the system significantly. 

PMID- 25571030
TI  - A hybrid feature-based segmentation and classification system for the computer
      aided self-diagnosis of otitis media.
AB  - We propose a novel hybrid otitis media (OM) computer aided detection (CAD)
      system, designed to aid in the self-diagnosis of various forms of OM. OM is a
      prevalent disease in both children and adults. Our system is able to
      differentiate normal ear from acute otitis media (AOM), otitis media with
      effusion (OME) and the multi-categories of chronic otitis media including
      perforation, retraction, cholesteatoma, etc. We propose a modified double active
      contour segmentation method designed for use with otoscope images, and enabled to
      handle user acquired data. To describe the visual symptoms (e.g., red, bulging,
      effusion, perforation, retraction, etc.) of otitis media accurately, we extract
      color, geometric and texture features by grid color moment, Gabor filter, local
      binary pattern and histogram of oriented gradients. A powerful classification
      structure based on Adaboost is used to select the most useful features and build
      a strong classifier. Our system achieves classification accuracy as high as
      88.06% and is suitable for real use. In addition, some interesting observations
      about OM otoscope images are also discussed. 

PMID- 25571029
TI  - A novel approach to malignant-benign classification of pulmonary nodules by using
      ensemble learning classifiers.
AB  - Computer-aided detection systems can help radiologists to detect pulmonary
      nodules at an early stage. In this paper, a novel Computer-Aided Diagnosis system
      (CAD) is proposed for the classification of pulmonary nodules as malignant and
      benign. The proposed CAD system using ensemble learning classifiers, provides an
      important support to radiologists at the diagnosis process of the disease,
      achieves high classification performance. The proposed approach with bagging
      classifier results in 94.7 %, 90.0 % and 77.8 % classification sensitivities for
      benign, malignant and undetermined classes (89.5 % accuracy), respectively. 

PMID- 25571031
TI  - Feature extraction and classification for ultrasound images of lumbar spine with
      support vector machine.
AB  - In this paper, we proposed a feature extraction and machine learning method for
      the classification of ultrasound images obtained from lumbar spine of pregnant
      patients in the transverse plane. A group of features, including matching values
      and positions, appearance of black pixels within predefined windows along the
      midline, are extracted from the ultrasound images using template matching and
      midline detection. Support vector machine (SVM) with Gaussian kernel is utilized
      to classify the bone images and interspinous images with optimal separation
      hyperplane. The SVM is trained with 800 images from 20 pregnant subjects and
      tested with 640 images from a separate set of 16 pregnant patients. A high
      success rate (97.25% on training set and 95.00% on test set) is achieved with the
      proposed method. The trained SVM model is further tested on 36 videos collected
      from 36 pregnant subjects and successfully identified the proper needle insertion
      site (interspinous region) on all of the cases. Therefore, the proposed method is
      able to identify the ultrasound images of lumbar spine in an automatic manner, so
      as to facilitate the anesthetists' work to identify the needle insertion point
      precisely and effectively. 

PMID- 25571032
TI  - Classifying bed inclination using pressure images.
AB  - Pressure ulcer is one of the most prevalent problems for bed-bound patients in
      hospitals and nursing homes. Pressure ulcers are painful for patients and costly
      for healthcare systems. Accurate in-bed posture analysis can significantly help
      in preventing pressure ulcers. Specifically, bed inclination (back angle) is a
      factor contributing to pressure ulcer development. In this paper, an efficient
      methodology is proposed to classify bed inclination. Our approach uses pressure
      values collected from a commercial pressure mat system. Then, by applying a
      number of image processing and machine learning techniques, the approximate
      degree of bed is estimated and classified. The proposed algorithm was tested on
      15 subjects with various sizes and weights. The experimental results indicate
      that our method predicts bed inclination in three classes with 80.3% average
      accuracy. 

PMID- 25571033
TI  - Development and validation of a fully automated system for detection and
      diagnosis of mammographic lesions.
AB  - We present a comprehensive and fully automated system for computer-aided
      detection and diagnosis of masses in mammograms. Novel methods for detection
      include: selection of suspicious focal areas based on analysis of the gradient
      vector field, rejection of oriented components of breast tissue using
      multidirectional Gabor filtering, and use of differential features for rejection
      of false positives (FPs) via clustering of the surrounding fibroglandular tissue.
      The diagnosis step is based on extraction of contour-independent features for
      characterization of lesions as benign or malignant from automatically detected
      circular and annular regions. A new unified 3D free-response receiver operating
      characteristic framework is introduced for global analysis of two binary
      categorization problems in cascade. In total, 3,080 suspicious focal areas were
      extracted from a set of 156 full-field digital mammograms, including 26 malignant
      tumors, 120 benign lesions, and 18 normal mammograms. The proposed system
      detected and diagnosed malignant tumors with a sensitivity of 0.96, 0.92, and
      0.88 at, respectively, 1.83, 0.46, and 0.45 FPs/image, with two stages of
      stepwise logistic regression for selection of features, a cascade of Fisher
      linear discriminant analysis and an artificial neural network with radial basis
      functions, and leave-one-patient-out cross-validation. 

PMID- 25571034
TI  - Automatic grading of placental maturity based on LIOP and fisher vector.
AB  - Currently, the evaluation of placental maturity has mainly focused on subjective
      measure, which highly depends on the observation and experiences of the
      clinicians and not reliable. This paper proposes a new method for grading
      placenta maturity in B-mod ultrasound (US) images automatically based on local
      intensity order pattern (LIOP) and fisher vector (FV). After extracting invariant
      LIOP feature from the affine covariant region, the feature is encoded by FV to
      improve the classification accuracy and reduce the processing time. Experimental
      results show the effectiveness of the proposed method with an accuracy of 0.9375,
      a sensitivity of 0.9804 and a specificity of 0.9375 for the placental maturity
      grading. Moreover, experimental results demonstrate that the LIOP feature
      outperforms the traditional SIFT feature for grading. 

PMID- 25571035
TI  - Random feature subspace ensemble based Extreme Learning Machine for liver tumor
      detection and segmentation.
AB  - This paper presents a new approach to detect and segment liver tumors. The
      detection and segmentation of liver tumors can be formulized as novelty detection
      or two-class classification problem. Each voxel is characterized by a rich
      feature vector, and a classifier using random feature subspace ensemble is
      trained to classify the voxels. Since Extreme Learning Machine (ELM) has
      advantages of very fast learning speed and good generalization ability, it is
      chosen to be the base classifier in the ensemble. Besides, majority voting is
      incorporated for fusion of classification results from the ensemble of base
      classifiers. In order to further increase testing accuracy, ELM autoencoder is
      implemented as a pre-training step. In automatic liver tumor detection, ELM is
      trained as a one-class classifier with only healthy liver samples, and the
      performance is compared with two-class ELM. In liver tumor segmentation, a semi
      automatic approach is adopted by selecting samples in 3D space to train the
      classifier. The proposed method is tested and evaluated on a group of patients'
      CT data and experiment show promising results. 

PMID- 25571036
TI  - An iterated Laplacian based semi-supervised dimensionality reduction for
      classification of breast cancer on ultrasound images.
AB  - The dimensionality reduction is an important step in ultrasound image based
      computer-aided diagnosis (CAD) for breast cancer. A newly proposed l2,1
      regularized correntropy algorithm for robust feature selection (CRFS) has
      achieved good performance for noise corrupted data. Therefore, it has the
      potential to reduce the dimensions of ultrasound image features. However, in
      clinical practice, the collection of labeled instances is usually expensive and
      time costing, while it is relatively easy to acquire the unlabeled or
      undetermined instances. Therefore, the semi-supervised learning is very suitable
      for clinical CAD. The iterated Laplacian regularization (Iter-LR) is a new
      regularization method, which has been proved to outperform the traditional graph
      Laplacian regularization in semi-supervised classification and ranking. In this
      study, to augment the classification accuracy of the breast ultrasound CAD based
      on texture feature, we propose an Iter-LR-based semi-supervised CRFS (Iter-LR
      CRFS) algorithm, and then apply it to reduce the feature dimensions of ultrasound
      images for breast CAD. We compared the Iter-LR-CRFS with LR-CRFS, original
      supervised CRFS, and principal component analysis. The experimental results
      indicate that the proposed Iter-LR-CRFS significantly outperforms all other
      algorithms. 

PMID- 25571037
TI  - An automatic bleeding detection scheme in wireless capsule endoscopy based on
      histogram of an RGB-indexed image.
AB  - Wireless capsule endoscopy (WCE) is one of the most effective technologies to
      diagnose gastrointestinal (GI) diseases, such as bleeding in GI tract. Because of
      long duration of WCE video containing large number images, it is a burden for
      clinician to detect diseases in real time. In this paper, an automatic bleeding
      image detection method is proposed utilizing construction of an index image
      incorporating certain level of information from each plane of RGB color space.
      Distinguishable color texture feature is developed from index image by histogram.
      Support vector machine (SVM) classifier is employed to detect bleeding and non
      bleeding images from WCE videos. From extensive experimentation on real time WCE
      video recordings, it is found that the proposed method can accurately detect
      bleeding images with high sensitivity and specificity. 

PMID- 25571038
TI  - Adaptation and evaluation of the multiple organs OSD for T2 MRI prostate
      segmentation.
AB  - This paper deals with the adaptation, the tuning and the evaluation of the
      multiple organs Optimal Surface Detection (OSD) algorithm for the T2 MRI prostate
      segmentation. This algorithm is initialized by first surface approximations of
      the prostate (obtained after a model adjustment), the bladder (obtained
      automatically) and the rectum (interactive geometrical model). These three organs
      are then segmented together in a multiple organs OSD scheme which proposes a
      competition between the gray level characteristics and some topological and
      anatomical information of these three organs. This method has been evaluated on
      the MICCAI Grand Challenge: Prostate MR Image Segmentation (PROMISE) 2012
      training dataset. 

PMID- 25571039
TI  - FPGA design for dual-spectrum Visual Scene Preparation in retinal prosthesis.
AB  - A method of Visual Scene Preparation for the patients suffering Retinitis
      Pigmentosa is implemented in hardware for the first time. The scene is captured
      with two cameras, one visible spectrum and one infra-red, in order to distinguish
      between the live and non-live objects. The live objects are subsequently
      emphasized in the output image, thus helping a patient to see the most
      significant detail with the healthy part of the retina. The implementation uses
      Verilog language and FPGA platform. A system prototype is analyzed and compared
      to MATLAB results. 

PMID- 25571040
TI  - Automatic segmentation of leg bones by using active contours.
AB  - In this paper, we present a new active contours model to segment human leg bones
      in computed tomography images that is based on a variable-weighted combination of
      local and global intensity. This model can split an object surrounded by both
      weak and strong boundaries, and also distinguish very adjacent objects with those
      boundaries. The ability of this model is required for segmentation in medical
      images, e.g., human leg bones, which are usually composed of highly inhomogeneous
      objects and where the distances among organs are very close. We developed an
      evolution equation of a level set function whose zero level set represents a
      contour. An initial contour is automatically obtained by applying a histogram
      based multiphase segmentation method. We experimented with computed tomography
      images from three patients, and demonstrate the efficiency of the proposed method
      in experimental results. 

PMID- 25571041
TI  - Abdominal wall extraction using constrained deformable model and abdominal
      context.
AB  - Information about abdominal wall can be used for many applications from organ
      segmentation, registration, and surgical simulation. The challenges exist in
      abdominal wall extraction due to its varieties in shapes, connection to the
      internal organs and anterior layer edge formed between the muscle and
      fascia/fatty layer, which may distract the shape model. In this paper we present
      an approach to the posterior abdominal wall extraction using the shape model and
      other abdominal context, particularly with the rib-spine bone information and the
      wall image features. The shape model is constructed based on the training
      abdominal walls that are delineated manually. After bone information being
      extracted, the wall shape deforms from the prior shape model using the snake,
      which is constrained by the bone context and guided by the processed image energy
      map with the aim of removing distracted image features of anterior abdominal wall
      and the outer region from the original map. Meanwhile, an overall convex shape is
      maintained by limiting the angles of the contour points. The proposed approach is
      tested on abdominal CT data which provides encouraging results. 

PMID- 25571042
TI  - Segmentation of renal parenchymal area from ultrasound images using level set
      evolution.
AB  - This paper presents a framework for segmentation of renal parenchymal area from
      ultrasound images based on a 2-step level set method. We used distance
      regularized level set evolution method to partition the kidney boundary, followed
      by region-scalable fitting energy minimization method to segment the kidney
      collecting system, and determined renal parenchymal area by subtracting the area
      of the collecting system from the gross kidney area. The proposed method
      demonstrated excellent validity and low inter-observer variability. 

PMID- 25571043
TI  - Statistical validation of automatic methods for hippocampus segmentation in MR
      images of epileptic patients.
AB  - Hippocampus segmentation is a key step in the evaluation of mesial Temporal Lobe
      Epilepsy (mTLE) by MR images. Several automated segmentation methods have been
      introduced for medical image segmentation. Because of multiple edges, missing
      boundaries, and shape changing along its longitudinal axis, manual outlining
      still remains the benchmark for hippocampus segmentation, which however, is
      impractical for large datasets due to time constraints. In this study, four
      automatic methods, namely FreeSurfer, Hammer, Automatic Brain Structure
      Segmentation (ABSS), and LocalInfo segmentation, are evaluated to find the most
      accurate and applicable method that resembles the bench-mark of hippocampus.
      Results from these four methods are compared against those obtained using manual
      segmentation for T1-weighted images of 157 symptomatic mTLE patients. For
      performance evaluation of automatic segmentation, Dice coefficient, Hausdorff
      distance, Precision, and Root Mean Square (RMS) distance are extracted and
      compared. Among these four automated methods, ABSS generates the most accurate
      results and the reproducibility is more similar to expert manual outlining by
      statistical validation. By considering p-value<;0.05, the results of performance
      measurement for ABSS reveal that, Dice is 4%, 13%, and 17% higher, Hausdorff is
      23%, 87%, and 70% lower, precision is 5%, -5%, and 12% higher, and RMS is 19%,
      62%, and 65% lower compared to LocalInfo, FreeSurfer, and Hammer, respectively. 

PMID- 25571044
TI  - An extension Gaussian mixture model for brain MRI segmentation.
AB  - The segmentation of brain magnetic resonance (MR) images into gray matter (GM),
      white matter (WM) and cerebrospinal fluid (CSF) has been an intensive studied
      area in the medical image analysis community. The Gaussian mixture model (GMM) is
      one of the most commonly used model to represent the intensity of different
      tissue types. However, as a histogram-based model, the spatial relationship
      between pixels is discarded in the GMM, making it sensitive to noise. Herein we
      present a new framework which aims to incorporate spatial information into the
      standard GMM, where each pixel is assigned its individual prior by leveraging its
      neighborhood information. Expectation maximization (EM) is modified to estimate
      the parameters of the proposed method. The method is validated on both synthetic
      and real brain MR images, showing its effectiveness in the segmentation task. 

PMID- 25571045
TI  - 3D+t brain MRI segmentation using robust 4D Hidden Markov Chain.
AB  - In recent years many automatic methods have been developed to help physicians
      diagnose brain disorders, but the problem remains complex. In this paper we
      propose a method to segment brain structures on two 3D multi-modal MR images
      taken at different times (longitudinal acquisition). A bias field correction is
      performed with an adaptation of the Hidden Markov Chain (HMC) allowing us to take
      into account the temporal correlation in addition to spatial neighbourhood
      information. To improve the robustness of the segmentation of the principal brain
      structures and to detect Multiple Sclerosis Lesions as outliers the Trimmed
      Likelihood Estimator (TLE) is used during the process. The method is validated on
      3D+t brain MR images. 

PMID- 25571046
TI  - A novel level set method for segmentation of left and right ventricles from
      cardiac MR images.
AB  - In this paper, we propose a novel level set method for segmentation of cardiac
      left and right ventricles based on the distance regularized level set evolution
      (DRLSE) framework [7] and the distance regularized two-layer level set (DR2LS)
      model [17]. First, DRLSE is applied to obtain a preliminary segmentation of left
      and right ventricles, which is then used to initialize the endocardial contour,
      which is represented by the zero level contour of the level set function in our
      method. Then, the epi-cardial contour is represented by a different level contour
      of the same level set function. These two level sets are optimized by an energy
      minimization process to best fit the true endocardium and epicardium. In order to
      ensure smoothly varying distance between the two level contours, we introduce a
      distance regularization constraint in the energy function. With the region
      scalable fitting (RSF) energy [8] as the data term, our method is able to deal
      with intensity inhomogeneities in the images, which is a main source of
      difficulty in image segmentation. Our method has been tested on cardiac MR images
      with promising results.

PMID- 25571047
TI  - Left ventricle segmentation by dynamic shape constrained random walks.
AB  - Accurate and robust extraction of the left ventricle (LV) cavity is a key step
      for quantitative analysis of cardiac functions. In this study, we propose an
      improved LV cavity segmentation method that incorporates a dynamic shape
      constraint into the weighting function of the random walks algorithm. The method
      involves an iterative process that updates an intermediate result to the desired
      solution. The shape constraint restricts the solution space of the segmentation
      result, such that the robustness of the algorithm is increased to handle
      misleading information that emanates from noise, weak boundaries, and clutter.
      Our experiments on real cardiac magnetic resonance images demonstrate that the
      proposed method obtains better segmentation performance than standard method. 

PMID- 25571048
TI  - A semi-automated image segmentation approach for computational fluid dynamics
      studies of aortic dissection.
AB  - Computational studies of aortic hemodynamics require accurate and reproducible
      segmentation of the aortic tree from whole body, contrast enhanced CT images.
      Three methods were vetted for segmentation. A semi-automated approach that
      utilizes denoising, the extended maxima transform, and a minimal amount of manual
      segmentation was adopted. 

PMID- 25571049
TI  - Adaptive automatic segmentation of Leishmaniasis parasite in Indirect
      Immunofluorescence images.
AB  - This paper describes the first steps for the automation of the serum titration
      process. In fact, this process requires an Indirect Immunofluorescence (IIF)
      diagnosis automation. We deal with the initial phase that represents the
      fluorescence images segmentation. Our approach consists of three principle
      stages: (1) a color based segmentation which aims at extracting the fluorescent
      foreground based on k-means clustering, (2) the segmentation of the fluorescent
      clustered image, and (3) a region-based feature segmentation, intended to remove
      the fluorescent noisy regions and to locate fluorescent parasites. We evaluated
      the proposed method on 40 IIF images. Experimental results show that such a
      method provides reliable and robust automatic segmentation of fluorescent
      Promastigote parasite. 

PMID- 25571050
TI  - Multi-focus image fusion using epifluorescence microscopy for robust vascular
      segmentation.
AB  - Automatic segmentation of three-dimensional mi-crovascular structures is needed
      for quantifying morphological changes to blood vessels during development,
      disease and treatment processes. Single focus two-dimensional epifluorescent
      imagery lead to unsatisfactory segmentations due to multiple out of focus vessel
      regions that have blurred edge structures and lack of detail. Additional
      segmentation challenges include varying contrast levels due to diffusivity of the
      lectin stain, leakage out of vessels and fine morphological vessel structure. We
      propose an approach for vessel segmentation that combines multi-focus image
      fusion with robust adaptive filtering. The robust adaptive filtering scheme
      handles noise without destroying small structures, while multi-focus image fusion
      considerably improves segmentation quality by deblurring out-of-focus regions
      through incorporating 3D structure information from multiple focus steps.
      Experiments using epifluorescence images of mice dura mater show an average of
      30.4% improvement compared to single focus microvasculature segmentation. 

PMID- 25571051
TI  - SVM-MRF segmentation of colorectal NBI endoscopic images.
AB  - In this paper we investigate a method for segmentation of colorectal Narrow Band
      Imaging (NBI) endoscopic images with Support Vector Machine (SVM) and Markov
      Random Field (MRF). SVM classifiers recognize each square patch of an NBI image
      and output posterior probabilities that represent how likely the given patch
      falls into a certain label. To prevent the spatial inconsistency between adjacent
      patches and encourage segmented regions to have smoother shapes, MRF is
      introduced by using the posterior outputs of SVMs as a unary term of MRF energy
      function. Segmentation results of 1191 NBI images are evaluated in experiments in
      which SVMs were trained with 480 trimmed NBI images and the MRF energy was
      minimized by an alpha - beta swap Graph Cut. 

PMID- 25571052
TI  - Longitudinal in-vivo volumetry study for porcine liver regeneration from CT data.
AB  - The use of hepatic-like cloned cord lining epithelial cells (CLEC) to enhance
      liver regeneration has been proposed, but has not been properly investigated in a
      large animal study. The paper presents a system developed for the longitudinal in
      vivo volumetry study on porcine liver regeneration from computed tomography (CT)
      data. In this system, a rough 3D liver volume is firstly automatically segmented
      by a 3D mesh deformation-based method. Then a refinement step to eliminate the
      segmentation error is carried out by a 3D post-editing tool, followed by mesh
      volume conversion and volume calculation. This system was applied in a pilot
      study, which was composed of 4/4 pigs in the Experimental/Control Groups, to
      measure liver volumes over pre- to post-operative time course. Experimental
      results suggest that (1) the developed system can perform CT-based porcine liver
      volumetry efficiently, and (2) the infusion of CLEC to liver remnant may
      potentially enhance the liver regeneration. 

PMID- 25571053
TI  - Segmentation and artifact removal in microwave-induced thermoacoustic imaging.
AB  - Microwave-induced thermoacoustic (TA) imaging combines the soft-tissue dielectric
      contrast of microwave excitation with the resolution of ultrasound for the goal
      of a safe, high resolution, and possibly portable imaging technique. However, the
      hybrid nature of this method introduces new image-reconstruction challenges in
      enabling sufficient accuracy and segmentation. In this paper, we propose a
      segmentation technique based on the polarity characteristic of TA signals. A
      wavelet analysis based method is proposed to identify reflection artifacts as
      well. The time-frequency feature of the signal is used to assist differentiating
      artifacts. Ex vivo verification with experimental data is also provided. 

PMID- 25571054
TI  - Video surveillance of epilepsy patients using color image processing.
AB  - This paper introduces a method for tracking patients under video surveillance
      based on a color marker system. The patients are not restricted in their
      movements, which requires a tracking system that can overcome non-ideal scenes
      e.g. occlusions, very fast movements, lighting issues and other moving objects.
      The suggested marker system consists of twelve unique markers that are located at
      each joint. By using a color marker system, each marker (if visible) can be found
      in every frame disregarding the possibility that it was occluded in the previous
      frame, compared to other tracking systems. 

PMID- 25571055
TI  - A novel genome-wide polyadenylation sites recognition system based on condition
      random field.
AB  - Polyadenylation including the cleavage of pre-mRNA and addition of a stretch of
      adenosines to the 3'-end is an essential step of pre-mRNA processing in
      eukayotes. The known regulatory role of polyadenylation in mRNA localization,
      stability, and translation and the emerging link between poly(A) and disease
      states underline the necessary to fully characterize polyadenylation sites.
      Several artificial intelligence methods have been proposed for poly(A) sites
      recognition. However, these methods are suitable to small subsets of genome
      sequences. It is necessary to propose a method for genome-wide recognition of
      poly(A) sites. Recent efforts have found a lot of poly(A) related factors on DNA
      level. Here, we proposed a novel genome-wide poly(A) recognition method based on
      the Condition Random Field (CRF) by integrating multiple features. Compared with
      the polya_svm (the most accurate program for prediction of poly(A) sites till
      date), our method had a higher performance with the area under ROC curve(0.8621
      versus 0.6796). The result suggests that our method is an effective method in
      genome wide poly(A) sites recognition. 

PMID- 25571057
TI  - Exploring regulatory elements in low-methylated regions for gene expression
      prediction.
AB  - Recent studies on methylomes have indicated that low-methylated regions (LMRs)
      are related to potential active distal regulatory regions. To further investigate
      the potential relation between LMRs and gene expression regulation, we propose a
      penalized logistic regression model to predict gene expression directional change
      based on computationally analyzed transcription factor binding sites in LMRs that
      are distinctive between two cell types. We evaluated this approach using the
      whole genome bisulphite sequencing and RNA-seq data of two cell types: adipose
      derived stem cells and iPSCs of adipose-derived stem cells. For Differentially
      Expressed (DE) genes with LMRs in their intergenic and/or genebody regions, our
      model obtained a 10-fold cross-validated AUC value of 0.88 for prediction of
      expression directional change. For DE genes with only LMRs in intergenic regions
      the corresponding AUC value is 0.84. 

PMID- 25571058
TI  - A model-based approach to transcription regulatory network reconstruction from
      time-course gene expression data.
AB  - Time-course gene expression profiling provides valuable data on dynamic behavior
      of cellular responses to external stimulation. Investigation of transcription
      factors (TFs) that regulate co-expressed genes in a dynamic process can reveal
      insights on the underlying molecular mechanisms. As the ChIP-seq technology is
      only suitable for a fraction of TFs in mammalian organisms, the computational
      identification of relevant TFs remains to be critical. We propose a regression
      based model to infer the functional binding sites of TFs from time-course gene
      expression profiles. Our approach incorporates an association strength for each
      potential TF and target gene pair based on computational analysis of binding
      sites in promoter sequences of co-expressed genes. Our model further uses the
      Lasso-penalized technique to search for the most informative TF-target pairs. The
      application of our method to a gene expression study on E2-induced apoptosis in a
      variant of MCF-7 cells revealed that the findings are biologically meaningful. 

PMID- 25571059
TI  - Comparison of clustering pipelines for the analysis of mass spectrometry imaging
      data.
AB  - Mass spectrometry imaging (MSI) is valuable for biomedical applications because
      it links molecular and morphological information. However, MSI datasets can be
      very large, and analyzing them to identify important biological patterns is a
      challenging computational problem. Many types of unsupervised analysis have been
      applied to MSI data, and in particular, clustering has recently gained attention
      for this application. In this paper, we present an exploratory study of the
      performance of different analysis pipelines using k-means and fuzzy k-means
      clustering. The results indicate the effects of different pre-processing and
      parameter selections on identifying biologically relevant patterns in MSI data. 

PMID- 25571056
TI  - A metabolic signature of colon cancer initiating cells.
AB  - Colon cancer initiating cells (CCICs) are more tumorigenic and metastatic than
      the majority of colorectal cancer (CRC) cells. CCICs have also been associated
      with stem cell-like properties. However, there is a lack of system-level
      understanding of what mechanisms distinguish CCICs from common CRC cells. We
      compared the transcriptomes of CD133+ CCICs and CD133- CRC cells from multiple
      sources, which identified a distinct metabolic signature for CD133(high) CCICs.
      High-resolution unbiased metabolomics was then performed to validate this CCIC
      metabolic signature. Specifically, levels of enzymes and metabolites involved in
      glycolysis, the citric acid (TCA) cycle, and cysteine and methionine metabolism
      are altered in CCICs. Analyses of the alterations further suggest an epigenetic
      link. This metabolic signature provides mechanistic insights into CCIC phenotypes
      and may serve as potential biomarkers and therapeutic targets for future CRC
      treatment. 

PMID- 25571060
TI  - Detecting vocalizations of individual monkeys in social groups.
AB  - Vocalization is an important clue in recognizing monkeys' behaviors. Previous
      studies have shown that the frequencies, the types and the lengths of
      vocalizations reveal significant information about social interactions in a group
      of monkeys. In this work, we describe a corpus of monkey vocalizations, recorded
      from Oregon National Primate Research Center with the goal of developing
      automatic methods for recognizing social behaviors of individuals in groups. The
      constraints of the problem necessitated using tiny low-power recorders, mounted
      on their collars. The recordings from each monkeys' recorder nonetheless contains
      vocalizations from not only the monkey wearing the recorder but also its spatial
      neighbors. The devices recorded vocalizations for two consecutive days, 12 hours
      each day, from each monkey in the group. Like in sensor networks, low power
      recorders are unreliable and have sample loss over long durations. Furthermore,
      the recordings contain high-levels of background noise, including clanging of
      metal collars against cages and conversations of caretakers. These practical
      issues poses an interesting challenge in processing the recordings. In this
      paper, we investigate our automated approaches to process the data efficiently,
      detect the vocalizations and align the recordings from the same sessions. 

PMID- 25571061
TI  - Novel prediction of anticancer drug chemosensitivity in cancer cell lines:
      evidence of moderation by microRNA expressions.
AB  - The objectives of this study are (1) to develop a novel "moderation" model of
      drug chemosensitivity and (2) to investigate if miRNA expression moderates the
      relationship between gene expression and drug chemosensitivity, specifically for
      HSP90 inhibitors applied to human cancer cell lines. A moderation model
      integrating the interaction between miRNA and gene expressions was developed to
      examine if miRNA expression affects the strength of the relationship between gene
      expression and chemosensitivity. Comprehensive datasets on miRNA expressions,
      gene expressions, and drug chemosensitivities were obtained from National Cancer
      Institute's NCI-60 cell lines including nine different cancer types. A workflow
      including steps of selecting genes, miRNAs, and compounds, correlating gene
      expression with chemosensitivity, and performing multivariate analysis was
      utilized to test the proposed model. The proposed moderation model identified 12
      significantly-moderating miRNAs: miR-15b*, miR-16-2*, miR-9, miR-126*, miR-129*,
      miR-138, miR-519e*, miR-624*, miR-26b, miR-30e*, miR-32, and miR-196a, as well as
      two genes ERCC2 and SF3B1 which affect chemosensitivities of Tanespimycin and
      Alvespimycin - both HSP90 inhibitors. A bootstrap resampling of 2,500 times
      validates the significance of all 12 identified miRNAs. The results confirm that
      certain miRNA and gene expressions interact to produce an effect on drug
      response. The lack of correlation between miRNA and gene expression themselves
      suggests that miRNA transmits its effect through translation inhibition/control
      rather than mRNA degradation. The results suggest that miRNAs could serve not
      only as prognostic biomarkers for cancer treatment outcome but also as
      interventional agents to modulate desired chemosensitivity. 

PMID- 25571062
TI  - Conduction block in novel cardiomyocyte electrical conduction line by
      photosensitization reaction.
AB  - We developed a novel cardiomyocyte electrical conduction line. We studied
      electrical conduction block by extra-cellular photosensitization reaction with
      this conduction line to study electrical blockade by the photosensitization
      reaction in vitro. 

PMID- 25571063
TI  - A smartphone based cardiac coherence biofeedback system.
AB  - Cardiac coherence biofeedback training consist on slowing one's breathing to 0.1
      Hz in order to simulate the baroreflex sensitivity and increase the respiratory
      sinus arrhythmia efficiency. Several studies have shown that these breathing
      exercises can constitute an efficient therapy in many clinical contexts like
      cardiovascular diseases, asthma, fibromyalgia or post-traumatic stress. Such a
      non-intrusive therapeutic solution needs to be performed on an 8 to 10 weeks
      period. Even if some heart rate variability based solutions exist, they presented
      some mobility constrain rendering these cardiac / respiratory control
      technologies more difficult to perform on a daily used. In this paper, we present
      a new simplified smartphone based solution allowing people to process efficient
      cardiac coherence biofeedback exercises. Based on photo-plethysmographic imaging
      through the smartphone camera, this sensor-less technology allows controlling
      cardiac coherence biofeedback exercises through a simplified heart rate
      variability algorithm. 

PMID- 25571064
TI  - Hemodynamic monitor for rapid, cost-effective assessment of peripheral vascular
      function.
AB  - Peripheral vascular diseases affect hundreds of millions of people worldwide and
      are often symptomless and undiagnosed. Early diagnosis is crucial for effective
      treatment and reducing personal and economic costs, particularly where early
      treatment is geared towards preventing lower extremity amputation. New diagnostic
      tools are needed to enable this earlier intervention. We have developed a new low
      cost, easy to use, non-invasive hemodynamic monitor, HeMo, to address this large
      and growing problem. Using a novel combination of impedance tomography and
      electrical volumetric measurements we can calculate real-time changes in
      peripheral blood volume. We believe that this work will lead to the availability
      of a fast, easy to use and cost-effective vascular assessment tool, dramatically
      shortening the time to diagnosis and subsequently intervention, dramatically
      improving the prognosis of affected patients. 

PMID- 25571065
TI  - Image-free evaluation of carotid artery stiffness using ARTSENS: a repeatability
      study.
AB  - Evaluation of arterial stiffness is significant in early detection and vascular
      diagnosis. We have developed and validated an image free system called ARTSENS
      for evaluation of carotid artery stiffness. In this paper, we present a detailed
      study on the repeatability of arterial stiffness measurements performed using
      ARTSENS. The study protocol was designed to emulate typical constraints
      encountered in field usage of ARTSENS as a screening tool. The intra operator
      variability (repeatability) of ARTSENS was verified by in-vivo measurements on 18
      subjects. Inter operator variability (reproducibility) was also studied. The
      ability of the instrument to give reliable measurements in both sitting and
      supine posture of the subject was verified. Further, the variation of arterial
      stiffness measurements over different times of the day was investigated to verify
      the ability of the instrument to give a practically usable stable measure of
      stiffness. The repeatability and reproducibility of ARTSENS measurements was
      found to be comparable to those provided by state of art image-based systems.
      Stiffness measurements provided by ARTSENS were found to be stable over a day
      indicating utility of the instrument in providing a quick and reliable measure of
      carotid artery stiffness. 

PMID- 25571066
TI  - Investigation of visually induced motion sickness in dynamic 3D contents based on
      subjective judgment, heart rate variability, and depth gaze behavior.
AB  - Visually induced motion sickness (VIMS) is an important safety issue in
      stereoscopic 3D technology. Accompanying subjective judgment of VIMS with
      objective measurement is useful to identify not only biomedical effects of
      dynamic 3D contents, but also provoking scenes that induce VIMS, duration of
      VIMS, and user behavior during VIMS. Heart rate variability and depth gaze
      behavior are appropriate physiological indicators for such objective observation.
      However, there is no information about relationship between subjective judgment
      of VIMS, heart rate variability, and depth gaze behavior. In this paper, we
      present a novel investigation of VIMS based on simulator sickness questionnaire
      (SSQ), electrocardiography (ECG), and 3D gaze tracking. Statistical analysis on
      SSQ data shows that nausea and disorientation symptoms increase as amount of
      dynamic motions increases (nausea: p<;0.005; disorientation: p<;0.05). To reduce
      VIMS, SSQ and ECG data suggest that user should perform voluntary gaze fixation
      at one point when experiencing vertical motion (up or down) and horizontal motion
      (turn left and right) in dynamic 3D contents. Observation of 3D gaze tracking
      data reveals that users who experienced VIMS tended to have unstable depth gaze
      than ones who did not experience VIMS. 

PMID- 25571067
TI  - Pattern classification of time plane features of ECG wave from cell-phone
      photography for machine aided cardiac disease diagnosis.
AB  - This article reports a robust technique for extracting time plane features of
      Electrocardiogram (ECG) from digital images of ECG paper strips. We concluded
      this article reporting performance evaluation of the system developed for machine
      aided cardiac disease detection. Mostly paper based ECG recordings are used in
      developing countries and digital photographs of different leads could easily be
      taken and sent with a mediocre cellular phone set. Apart from extracting the
      features, the proposed system detects cardiac axis deviation and diagnose if Left
      or Right Bundle Branch Blockage (LBBB or RBBB) is present while fed with the
      digital photographs of different leads of ECG strips. Preprocessing of the low
      resolution images involves background grid line noise removal, adaptive image
      binarization by Sauvola's method and Bresenham's line joining algorithm to link
      the ECG signature, if broken. Pattern extraction mainly delineate the time plane
      features like P wave, QRS complex and T wave using water reservoir based pattern
      recognition techniques and Discrete Wavelet Transform (DWT). Cardiac axis
      deviation detection is done by checking the overall voltage levels of QRS
      complexes of lead I, II and III. Having the knowledge of cardiac axis completes
      the requirements to comment on the cardiac blockage like Left or Right Bundle
      Branch Blockage (LBBB or RBBB). Thus, the proposed algorithm is primarily
      developed for machine aided diagnosis of LBBB or RBBB from the digital
      photographs of ECG paper strips. 

PMID- 25571068
TI  - Design an easy-to-use infection screening system for non-contact monitoring of
      vital-signs to prevent the spread of pandemic diseases.
AB  - The outbreak of infectious diseases such as influenza, dengue fever, and severe
      acute respiratory syndrome (SARS) are threatening the global health. Especially,
      developing countries in the South-East Asia region have been at serious risk.
      Rapid and highly reliable screening of infection is urgently needed during the
      epidemic season at mass gathering places, such as airport quarantine facilities,
      public health centers, and hospital outpatients units, etc. To meet this need,
      our research group is currently developing a multiple vital-signs based infection
      screening system that can perform human medical inspections within 15 seconds.
      This system remotely monitors facial temperature, heart and respiration rates
      using a thermopile array and a 24-GHz microwave radar, respectively. In this
      work, we redesigned our previous system to make a higher performance with a user
      friendly interface. Moreover, the system newly included a multivariable logistic
      regression model (MLRM) to determine the possibility of infection. We tested the
      system on 34 seasonal influenza patients and 35 normal control subjects at the
      Japan Self-Defense Forces Central Hospital. The sensitivity and specificity of
      the screening system using the MLRM were 85.3% and 88.6%, respectively. 

PMID- 25571070
TI  - An ocular compression device for reduction of elevated post anesthetic
      intraocular pressure.
AB  - Rise in Intra Ocular Pressure (IOP), after administration of regional ophthalmic
      anesthesia for surgery, is a commonly observed clinical phenomenon. Rise in IOP
      increases risk of retinal ischemia and leads to surgical complications. The
      current clinical practice for reduction of IOP, after delivery of local
      anesthesia, is manually administered digital compression. The highly subjective
      nature of manual compression, results in unknown duration and magnitude of the
      pressure applied, thus limiting the clinical effectiveness of the procedure. The
      work presented here addresses the need for a device that delivers all the
      benefits of digital compression, while eliminating the uncertainty and risks
      involved. Design, development and clinical validation of an air pressure based
      compression device have been presented in this paper. This device makes the
      compression procedure safe and reliable by quantifying all compression parameters
      applied and considering safety limits for individual subjects. 

PMID- 25571069
TI  - Synthetic optimization of air turbine for dental handpieces.
AB  - A synthetic optimization of Pelton air turbine in dental handpieces concerning
      the power output, compressed air consumption and rotation speed in the mean time
      is implemented by employing a standard design procedure and variable limitation
      from practical dentistry. The Pareto optimal solution sets acquired by using the
      Normalized Normal Constraint method are mainly comprised of two piecewise
      continuous parts. On the Pareto frontier, the supply air stagnation pressure
      stalls at the lower boundary of the design space, the rotation speed is a
      constant value within the recommended range from literature, the blade tip
      clearance insensitive to while the nozzle radius increases with power output and
      mass flow rate of compressed air to which the residual geometric dimensions are
      showing an opposite trend within their respective "pieces" compared to the nozzle
      radius. 

PMID- 25571071
TI  - Development and validation of a tactile sensitivity scale for peripheral
      neuropathy screening.
AB  - One of the difficult of the hands peripheral neuropathy screening uncertainty is
      that the current diagnosis is based not on assessments obtained by accurate and
      repeatable devices, but mostly on the clinical examination. So, in this paper the
      authors present a tactile pins-array scale determined with well-defined
      parameters assessed by non-invasive DITA device (Dynamic Investigation Test-rig
      on hAptics). This high resolution scale permits to screen the gradual tactile
      sensory deficit of patients affected by neuropathic diseases. The work has
      started with an experiment on healthy subjects penalizing their bare finger
      tactile sensitivity with five different pins-arrays. So, a pins-array scale
      divided in six levels (grouped in three ranges: low, uncertain and normal tactile
      sensitivity) was created. The scale was validated with a pilot study on six
      subjects affected by neuropathic disease. Results show an important role of the
      scale, supporting the clinical screening and reducing the uncertainty. 

PMID- 25571072
TI  - Dual patch antenna sensor for pneumothorax diagnosis: sensitivity and performance
      study.
AB  - Pneumothorax may cause serious health problems and often death if medical and
      surgical treatment is delayed. The absence of reliable, safe, portable and easy
      to-use equipment in the ambulance is the primary clinical motivation of this
      work. We investigate pneumothorax diagnostic performance and sensitivity of a
      dual patch antenna system (sensor). The operation frequency range is set to 1-4
      GHz. Parametric study is conducted using simplified rectangular tissue numerical
      models. Variation of S12 parameter, related to frequency, is compared in order to
      distinguish healthy and pneumothorax cases, reaching a difference of 20.1 dB, at
      1.87 GHz. MRI-based anatomic models are also modified in order to simulate
      pneumothorax incident, in realistic clinical case. The best performance
      configuration scenario is applied onto the modified anatomic models, revealing
      satisfactory sensor performance (7.1 dB, at 2.3 GHz). Sensor diagnostic ability
      reaches 1 cm of air thickness. The paper concludes with proposed design
      specifications for thorax experimental phantom. 

PMID- 25571073
TI  - Detection of diabetic foot hyperthermia by infrared imaging.
AB  - In diabetic foot, the occurrence of an ulcer is often associated with
      hyperthermia. Hyperthermia is defined as a temperature greater than 2.2 degrees C
      in a given region of one of the foot compared to the temperature of the same
      region of the contralateral foot. Unfortunately, hyperthermia is not yet assessed
      in current diabetic foot therapy. In this paper, we propose an easy way to detect
      a possible hyperthermia by using an infrared camera. A specific acquisition
      protocol of the thermal images is proposed. A dedicated image analysis is
      developed: it is composed of a contour detection of the 2 feet using the Chan and
      Vese active contour method associated to the ICP rigid registration technique.
      Among 85 type II diabetes persons recruited in the Dos de Mayo hospital in Lima,
      Peru, 9 individuals show significant hyperthermia. It is expected that the new
      possibility of detecting hyperthermia in hospitals or in diabetic health centers
      which is now available, thanks to the proposed method, will help in reducing foot
      ulcer occurrence for diabetic persons.

PMID- 25571074
TI  - Postprandial blood glucose control in type 1 diabetes for carbohydrates with
      varying glycemic index foods.
AB  - Treatment of type 1 diabetes consists of maintaining postprandial normoglycemia
      using the correct prandial insulin dose according to food intake. Nonetheless, it
      is hardly achieved in practice, which results in several diabetes-related
      complications. In this study we present a feedforward plus feedback blood glucose
      control system that considers the glycemic index of foods. It consists of a
      preprandial insulin bolus whose optimal bolus dose and timing are stated as a
      minimization problem, which is followed by a postprandial closed-loop control
      based on model predictive control. Simulation results show that, for a
      representative carbohydrate intake of 50 g, the present control system is able to
      maintain postprandial glycemia below 140 mg/dL while preventing postprandial
      hypoglycemia as well. 

PMID- 25571075
TI  - Reducing risk of closed loop control of blood glucose in artificial pancreas
      using fractional calculus.
AB  - Healthcare costs in the US are among the highest in the world. Chronic diseases
      such as diabetes significantly contribute to these extensive costs. Despite
      technological advances to improve sensing and actuation devices, we still lack a
      coherent theory that facilitates the design and optimization of efficient and
      robust medical cyber-physical systems for managing chronic diseases. In this
      paper, we propose a mathematical model for capturing the complex dynamics of
      blood glucose time series (e.g., time dependent and fractal behavior) observed in
      real world measurements via fractional calculus concepts. Building upon our time
      dependent fractal model, we propose a novel model predictive controller for an
      artificial pancreas that regulates insulin injection. We verify the accuracy of
      our controller by comparing it to conventional non-fractal models using real
      world measurements and show how the nonlinear optimal controller based on fractal
      calculus concepts is superior to non-fractal controllers in terms of average risk
      index and prediction accuracy. 

PMID- 25571077
TI  - Computation of reduced energy input current stimuli for neuron phase models.
AB  - A regularly spiking neuron can be studied using a phase model. The effect of an
      input stimulus current on the phase time derivative is captured by a phase
      response curve. This paper adapts a technique that was previously applied to
      conductance-based models to discover optimal input stimulus currents for phase
      models. First, the neuron phase response theta(t) due to an input stimulus
      current i(t) is computed using a phase model. The resulting theta(t) is taken to
      be a reference phase r(t). Second, an optimal input stimulus current i(*)(t) is
      computed to minimize a weighted sum of the square-integral 'energy' of i(*)(t)
      and the tracking error between the reference phase r(t) and the phase response
      due to i(*)(t). The balance between the conflicting requirements of energy and
      tracking error minimization is controlled by a single parameter. The generated
      optimal current i(*)t) is then compared to the input current i(t) which was used
      to generate the reference phase r(t). This technique was applied to two neuron
      phase models; in each case, the current i(*)(t) generates a phase response
      similar to the reference phase r(t), and the optimal current i(*)(t) has a lower
      'energy' than the square-integral of i(t). For constant i(t), the optimal current
      i(*)(t) need not be constant in time. In fact, i(*)(t) is large (possibly even
      larger than i(t)) for regions where the phase response curve indicates a stronger
      sensitivity to the input stimulus current, and smaller in regions of reduced
      sensitivity. 

PMID- 25571076
TI  - Multi-model data fusion to improve an early warning system for hypo
      /hyperglycemic events.
AB  - Correct predictions of future blood glucose levels in individuals with Type 1
      Diabetes (T1D) can be used to provide early warning of upcoming hypo
      /hyperglycemic events and thus to improve the patient's safety. To increase
      prediction accuracy and efficiency, various approaches have been proposed which
      combine multiple predictors to produce superior results compared to single
      predictors. Three methods for model fusion are presented and comparatively
      assessed. Data from 23 T1D subjects under sensor-augmented pump (SAP) therapy
      were used in two adaptive data-driven models (an autoregressive model with output
      correction - cARX, and a recurrent neural network - RNN). Data fusion techniques
      based on i) Dempster-Shafer Evidential Theory (DST), ii) Genetic Algorithms (GA),
      and iii) Genetic Programming (GP) were used to merge the complimentary
      performances of the prediction models. The fused output is used in a warning
      algorithm to issue alarms of upcoming hypo-/hyperglycemic events. The fusion
      schemes showed improved performance with lower root mean square errors, lower
      time lags, and higher correlation. In the warning algorithm, median daily false
      alarms (DFA) of 0.25%, and 100% correct alarms (CA) were obtained for both event
      types. The detection times (DT) before occurrence of events were 13.0 and 12.1
      min respectively for hypo-/hyperglycemic events. Compared to the cARX and RNN
      models, and a linear fusion of the two, the proposed fusion schemes represents a
      significant improvement. 

PMID- 25571078
TI  - A mean field model for neural-metabolic homeostatic coupling in burst
      suppression.
AB  - Burst suppression is an inactivated brain state in which the electroencephalogram
      is characterized by intermittent periods of isoelectric quiescence. Recent
      modeling studies have suggested an important role for brain metabolic processes
      in governing the very slow time scales that underlie the duration of bursts and
      suppressions. In these models, a reduction in metabolism leads to substrate
      depletion and consequent suppression of action potential firing. Such a mechanism
      accounts for the appearance of burst suppression when metabolism is directly down
      regulated. However, in many cases such as general anesthesia, metabolic down
      regulation occurs in part as a homeostatic consequence of reduced neuronal
      activity. Here, we develop a mean-field model for neuronal activity with
      metabolic homeostatic mechanisms. We show that with such mechanisms, a simple
      reduction in neuronal activity due, for example, to increased neuronal
      inhibition, will give rise to bistability due to a bifurcation in the combined
      neuronal and metabolic dynamics. The model reconciles a purely metabolic
      mechanism for burst suppression with one that includes important dynamical
      feedback from the neuronal activity itself. The resulting fast-slow dynamical
      description forms a useful model for further development of novel methods for
      managing burst suppression clinically. 

PMID- 25571079
TI  - Electrical stimulation of neural tissue modeled as a cellular composite: point
      source electrode in an isotropic tissue.
AB  - Standard volume conductor models of neural electrical stimulation assume that the
      electrical properties of the tissue are well described by a conductivity that is
      smooth and homogeneous at a microscopic scale. However, neural tissue is composed
      of tightly packed cells whose membranes have markedly different electrical
      properties to either the intra- or extracellular space. Consequently, the
      electrical properties of tissue are highly heterogeneous at the microscopic
      scale: a fact not accounted for in standard volume conductor models. Here we
      apply a recently developed framework for volume conductor models that accounts
      for the cellular composition of tissue. We consider the case of a point source
      electrode in tissue comprised of neural fibers crossing each other equally in all
      directions. We derive the tissue admittivity (that replaces the standard tissue
      conductivity) from single cell properties, and then calculate the extracellular
      potential. Our findings indicate that the cellular composition of tissue affects
      the spatiotemporal profile of the extracellular potential. In particular, the
      full solution asymptotically approaches a near-field limit close to the electrode
      and a far-field limit far from the electrode. The near-field and far-field
      approximations are solutions to standard volume conductor models, but differ from
      each other by nearly an order or magnitude. Consequently the full solution is
      expected to provide a more accurate estimate of electrical potentials over the
      full range of electrode-neurite separations. 

PMID- 25571080
TI  - A systems identification approach to estimating the connectivity in a neuronal
      population model.
AB  - Mapping the brain and its complex networked structure has been one of the most
      researched topics in the last decade and continues to be the path towards
      understanding brain diseases. In this paper we present a new approach to
      estimating the connectivity between neurons in a network model. We use systems
      identification techniques for nonlinear dynamic models to compute the synaptic
      connections from other pre-synaptic neurons in the population. We are able to
      show accurate estimation even in the presence of model error and inaccurate
      assumption of post-synaptic potential dynamics. This allows to compute the
      connectivity matrix of the network using a very small time window of membrane
      potential data of the individual neurons. The specificity and sensitivity
      measures for randomly generated networks are reported. 

PMID- 25571081
TI  - Braincubator: an incubation system to extend brain slice lifespan for use in
      neurophysiology.
AB  - In vitro brain slice preparations are instrumental in developing our
      understanding of the nervous system. However, the current lifespan of an acute
      brain slice is limited to approximately 6-12 hours. This reduces potential
      experimentation time and leads to considerable waste of neural tissue. We have
      designed, developed and tested a novel incubation system capable of extending the
      lifespan of these brain slices. This is done by controlling the temperature and
      pH of the artificial cerebral spinal fluid in which the slices are incubated
      while continuously passing the fluid through a UVC filtration system. This system
      is capable of maintaining extremely low bacterial levels and significantly
      extending the brain slice lifespan to at least 24 hours. Brain slice viability
      was validated through electrophysiological recordings as well as live/dead cell
      assays. 

PMID- 25571082
TI  - Consideration of the functional relationship between cortex and motor periphery
      improves offline decoding performance.
AB  - Decoding neural activity to control prosthetic devices or computer interfaces is
      a promising avenue for rehabilitating individuals with amputation or severe
      spinal cord injury. In most cases, however, the local functionality of the neural
      tissue is not considered when designing a decoding algorithm. One way to
      characterize the functional specificity of a local region of motor cortex, and
      its output effects, is to use intracortical microstimulation. In this study, we
      examined how the results of an ICMS experiment relate to the performance of
      various offline decoders. We found evidence that units from electrodes with
      stimulation effects decode kinematics better than units from electrodes without
      stimulation effects. 

PMID- 25571083
TI  - Ultra-long term stability of single units using chronically implanted
      multielectrode arrays.
AB  - Recordings from chronically implanted multielectrode arrays have become prevalent
      in both neuroscience and neural engineering experiments. To date, however, the
      extent to which populations of single-units remain stable over long periods of
      time has not been well characterized. In this study, neural activity was recorded
      from a Utah multielectrode array implanted in the primary motor cortex of a
      rhesus macaque during 18 recording sessions spanning nine months. We found that
      67% of the units were stable through the first 15 days, 31% of units were stable
      through 47 days, 21% of units were stable through 106 days, and 8% of units were
      stable over 9 months. Thus not only were units stable over a timescale of several
      months, but units stable over 2 months were more likely to remain stable in the
      next 2 months. 

PMID- 25571084
TI  - Recording place cells from multiple sub-regions of the rat hippocampus with a
      customized micro-electrode array.
AB  - The hippocampus is a subcortical structure which is involved in memory function.
      There is a considerable amount of evidence available which indicates that the
      hippocampal system is necessary for effective spatial learning in rodents and
      short-term topographical memory in human. Recordings of neural activities from
      the hippocampus of behaving animals can help us to understand how spatial
      information is encoded and processed by the hippocampus. In this work, we
      designed a triple-region microelectrode array (MEA) which took into concern the
      anatomical structures of the rat hippocampus. The array was composed of 16
      stainless steel wires which were arranged into three groups that differed in
      length. Each group targeted one subregion of the hippocampus. The array was
      chronically implanted into the rat hippocampus through craniotomy. Neural
      activities were monitored both during the implantation and after recovery. The
      triple-region MEA was capable of recording unitary activities from multiple
      subregions of the rat hippocampus and the spatial distribution of firing rates
      were analyzed while the animal freely explored in the environment. 

PMID- 25571085
TI  - Effects of astrocytic mechanisms on neuronal hyperexcitability.
AB  - While originally astrocytes have been thought to only act as support to neurons,
      recent studies have implicated them in multiple active roles, including the
      ability to moderate or alter neuronal firing patterns and to possibly be involved
      in both the prevention and propagation of epileptic seizures. In this study we
      propose a new model to incorporate pyramidal cells and interneurons (a common
      neural circuit in CA3 hippocampal slices) as well as a model of astrocyte. As
      both potassium and calcium ions have been shown to potentially affect neuronal
      hyperexcitability, the astrocytic model has both mechanisms--the clearance of
      potassium through potassium channels (such as KIR, KDR and sodium-potassium
      pump), and the influence of astrocyte in the synapse (forming the tripartite
      synapse with calcium-glutamate interactions). Preliminary findings of the model
      results show that when potassium conductances in the astrocyte are decreased, it
      results in the accumulation of extracellular potassium, leading to both
      spontaneous discharges and depolarization block, while the alteration of normal
      calcium response in the astrocyte can lead to just hyperexcitable conditions
      without the depolarization block.

PMID- 25571086
TI  - An in silico approach for pre-surgical evaluation of an epileptic cortex.
AB  - Clinical evidence indicates that a third of patients with epilepsy are refractory
      to anti-epileptic drug treatment. For some of these patients better seizure
      control can be achieved by surgical treatment in which the seizure focus is
      localised and resected while avoiding injury to crucial cortical tissues. In this
      paper, non-seizure (interictal) epoch of electrographic recording was used to
      calculate the functional synchrony between different cortical regions. This
      synchrony measure was then used as the connectivity parameter in a computational
      model of transitions to a seizure like state. The seizure focus was localised
      using this model and the surgical intervention procedure was simulated. It was
      shown that the in silico removal of a subset of seizure focus can decrease the
      likelihood of a seizure in the model. The in silico results were also compared
      with the clinical outcomes and a convincing agreement was shown for five out of
      six patients; sixth being a counter-example. These methods may aid in the
      identification of the seizure onset zone using the interictal electrographic
      data. Moreover, it may facilitate neurosurgeons to investigate alternative
      cortical tissues to operate on if the seizure focus cannot be operated. 

PMID- 25571087
TI  - Oscillations in human orbitofrontal cortex during even chance gambling.
AB  - Evaluating value and risk as well as comparing expected and actual outcomes is
      the crux of decision making and reinforcement based learning. In this study, we
      record from stereotactic electroencephalograph depth electrodes in a human
      subject in numerous areas in the brain. We focus on the lateral and medial
      orbitofrontal cortex while they perform a gambling task involving betting on a
      high card. Preliminary time-frequency analysis shows modulations in the 5-15 Hz
      band that is well synced to the different events of the task. These oscillations
      increase in both high betting scenarios as well as in losing scenarios though
      their effects cannot be decoupled. However, the activity between lateral and
      medial orbitofrontal cortex is a lot more homogenous than previously seen.
      Additionally, the timing of some of these oscillations occurs before even a
      response in the visual cortex. This evidence hints that these areas encode priors
      that influence our decision in future statistically ambiguous scenarios.

PMID- 25571088
TI  - Evaluation and comparison of effective connectivity during simple and compound
      limb motor imagery.
AB  - Motor imagery (MI) has been demonstrated beneficial in motor rehabilitation in
      patients with movement disorders. In contrast with simple limb motor imagery,
      less work was reported about the effective connectivity networks of compound limb
      motor imagery which involves several parts of limbs. This work aimed to
      investigate the differences of information flow patterns between simple limb
      motor imagery and compound limb motor imagery. Ten subjects participated in the
      experiment involving three tasks of simple limb motor imagery (left hand, right
      hand, feet) and three tasks of compound limb motor imagery (both hands, left hand
      combined with right foot, right hand combined with left foot). The causal
      interactions among different neural regions were evaluated by Short-time Directed
      Transfer Function (SDTF). Quite different from the networks of simple limb motor
      imagery, more effective interactions overlying larger brain regions were observed
      during compound limb motor imagery. These results imply that there exist
      significant differences in the patterns of EEG activity flow between simple limb
      motor imagery and compound limb motor imagery, which present more complex
      networks and could be utilized in motor rehabilitation for more benefit in
      patients with movement disorders. 

PMID- 25571089
TI  - Investigating the neural basis of cooperative joint action. An EEG hyperscanning
      study.
AB  - The aim of the present study is to investigate the neurophysiological basis of
      the cognitive functions underlying the execution of joint actions, by means of
      the recent technique called hyperscanning. Neuroelectrical hyperscanning is based
      on the simultaneous recording of brain activity from multiple subjects and
      includes the analysis of the functional relation between the brain activity of
      all the interacting individuals. We recorded simultaneous high density
      electroencephalography (hdEEG) from 16 pairs of subjects involved in a
      computerized joint action paradigm, with controlled levels of cooperation.
      Results of cortical connectivity analysis returned significant differences, in
      terms of inter-brain functional causal links, between the condition of
      cooperative joint action and a condition in which the subjects were told they
      were interacting with a PC, while actually interacting with another human
      subject. Such differences, described by selected brain connectivity indices,
      point toward an integration between the two subjects' brain activity in the
      cooperative condition, with respect to control conditions. 

PMID- 25571090
TI  - Investigation of P300 response characteristics through human color vision-based
      visual stimulation.
AB  - In this study, we propose visual stimulation based on the primary colors (red,
      green, and blue) in order to investigate the characteristics of the P300
      response. Eleven healthy volunteers participated in our experiment, and their
      brain signals were recorded by electroencephalography (EEG). Using two basic
      measures referred to as 'on-peak' and 'off-peak' for comparison of the P300
      response among the participants, we found that the P300 response varies depending
      on the color of the stimulus. The results of this investigation are expected to
      contribute to various existing and future EEG-based applications. 

PMID- 25571091
TI  - Three-layer-isotropic skull conductivity representation in the EEG forward
      problem using spherical head models.
AB  - We study the influence of different conductivity models within the framework of
      electroencephalogram (EEG) source localization on the white matter and skull
      areas. Particularly, we investigate five different spherical models having either
      isotropic or anisotropic conductivity for both considered areas. To this end, the
      anisotropic finite difference reciprocity method is used for solving the EEG
      forward problem. We evaluate a model of a numeric skull conductivity in terms of
      the minimum dipole localization/orientation error. As a result, both considered
      models of the skull reach the lowest dipole localization error (less than 6 mm),
      namely: i) single anisotropic layer and ii) three isotropic layers (hard
      bone/spongy bone/hard bone). Additionally, two different electrode configurations
      (10-20 and 10-10 systems) are tested showing that the error decreases almost as
      much as twice for the latter one though the computational burden significantly
      increases.

PMID- 25571092
TI  - Processing movement related cortical potentials in EEG signals for identification
      of slow and fast movements.
AB  - The extraction of intended kinetic information from an EEG signal can have
      several applications related to the rehabilitation for subjects with various
      neurological disorders. However, the task is mainly constrained by the low signal
      to-noise ratio for the EEG signals. It is well known that the cortical activity
      takes place at a very low frequency since it is characterized by the dropping of
      movement related cortical potential (MRCP) across the sampled EEG signal. The
      strong variations in the MRCP is indicative of the noise due to various sources.
      The aim of this work is to remove this noise from the EEG signals using empirical
      mode decomposition, which decomposes a signal into harmonics (intrinsic mode
      functions--IMF) of various frequencies. The IMFs pertaining to small frequencies
      are later used for features extraction where we extract the spatial and spectral
      features from the selected IMFs. The features are later used for classification
      using support vector machines (SVM). Our experiments show superior results to the
      benchmark method for the underlying dataset that has been used in this research.

PMID- 25571094
TI  - Fractional dynamical model for neurovascular coupling.
AB  - The neurovascular coupling is a key mechanism linking the neural activity to the
      hemodynamic behavior. Modeling of this coupling is very important to understand
      the brain function but it is at the same time very complex due to the complexity
      of the involved phenomena. Many studies have reported a time delay between the
      neural activity and the cerebral blood flow, which has been described by adding a
      delay parameter in some of the existing models. An alternative approach is
      proposed in this paper, where a fractional system is used to model the
      neurovascular coupling. Thanks to its nonlocal property, a fractional derivative
      is suitable for modeling the phenomena with delay. The proposed model is coupled
      with the first version of the well-known balloon model, which relates the
      cerebral blood flow to the Blood Oxygen Level Dependent (BOLD) signal measured
      using functional Magnetic Resonance Imaging (fMRI). Through some numerical
      simulations, the properties of the fractional model are explained and some
      preliminary comparisons to a real BOLD data set are provided. 

PMID- 25571095
TI  - Influence of anisotropic white matter modeling on EEG source localization.
AB  - We study the influence of the anisotropic white matter within the
      ElectroEncephaloGraphy source localization problem. To this end, we consider
      three cases of the anisotropic white matter modeled in two concrete cases: by
      fixed or variable ratio. We extract information about highly anisotropic areas of
      the white matter from real Diffusion Weighted Imaging data. To validate the
      compared anisotropic models, we introduce the localization dipole and orientation
      errors. Obtained results show that the white matter model with a fixed
      anisotropic ratio leads to values of dipole localization error close to 1cm and
      may be enough in those cases avoiding localized analysis of neural brain
      activity. In contrast, modeling based on the anisotropic variable rate assumption
      becomes important in tasks regarding analysis and localization of deep sources
      neighboring the white matter tissue. 

PMID- 25571093
TI  - Dual logic and dual neural basis for reciprocal social interaction in eye
      contact.
AB  - Dyadic brain interactions during eye contact engage multiple processes and
      recruit multiple networks. To fully characterize these concurrent activities,
      it's essential to establish the neural basis for reciprocal social interaction.
      So far most approaches in this pursuit suffered from the limitations in either
      insufficient dyadic test instruments or entwined reciprocal and non-reciprocal
      cerebral responses. To address these two challenges, this study not only employed
      a dual-head coil to directly acquire dyadic fMRI data, but also developed a dual
      logic to deductively untwine the reciprocal social interactive state and non
      reciprocal affective state in cerebral responses. As results, a data-driven
      neural basis for visual reciprocal interaction is derived, which mainly consists
      of imitation-empathy network and mentalizing network to facilitate the exogenous
      and endogenous dual processes. Applications of the neural basis in extracting
      dyadic network synchronizations are exemplified. In addition, the dual logic
      formulated emergence of the endogenous process and predicted the default-mode
      network. 

PMID- 25571096
TI  - Pattern discrimination of neuroelectric waveforms evoked by synchronized visuo
      motor integration.
AB  - Today, there is a significant demand for fast, accurate, and automated methods
      for the discrimination of latent patterns in neuroelectric waveforms. One of the
      main challenges is the development of efficient feature extraction tools to
      utilize the rich spatio-temporal information inherent in large scale human
      electrocortical activity. In this paper, our aim is to isolate the most suitable
      feature extraction method for accurate classification of EEG data related to
      distinct modes of sensorimotor integration. Our results demonstrate that with
      some user-dependent input for feature space constraint, a simple classification
      framework can be developed to accurately distinguish between brain electrical
      activity patterns during two distinct conditions. 

PMID- 25571097
TI  - Using Dynamic Bayesian Networks for modeling EEG topographic sequences.
AB  - In this work we present a methodology for modeling the trajectory of EEG
      topography over time, using Dynamic Bayesian Networks (DBNs). Based on the
      microstate model we are using DBNs to model the evolution of the EEG topography.
      Analysis of the microstate model is being usually limited in the wide band signal
      or an isolated band. We are using Coupled Hidden Markov Models (CHMM) and a two
      level influence model in order to model the temporal evolution and the coupling
      of the topography states in three bands, delta, theta and alpha. We are applying
      this methodology for the classification of target and non-target single trial
      from a visual detection task. The results indicate that taking under
      consideration the interaction among the different bands improves the
      classification of single trials. 

PMID- 25571098
TI  - Simultaneous blind separation and clustering of coactivated EEG/MEG sources for
      analyzing spontaneous brain activity.
AB  - Analysis of the dynamics (non-stationarity) of functional connectivity patterns
      has recently received a lot of attention in the neuroimaging community. Most
      analysis has been using functional magnetic resonance imaging (fMRI), partly due
      to the inherent technical complexity of the electro- or magnetoencephalography
      (EEG/MEG) signals, but EEG/MEG holds great promise in analyzing fast changes in
      connectivity. Here, we propose a method for dynamic connectivity analysis of
      EEG/MEG, combining blind source separation with dynamic connectivity analysis in
      a single probabilistic model. Blind source separation is extremely useful for
      interpretation of the connectivity changes, and also enables rejection of
      artifacts. Dynamic connectivity analysis is performed by clustering the
      coactivation patterns of separated sources by modeling their variances.
      Experiments on resting-state EEG show that the obtained clusters correlate with
      physiologically meaningful quantities. 

PMID- 25571099
TI  - Localized cortical dipole imaging using a small number of electrodes based on
      independent component analysis.
AB  - The spatial resolution of scalp potential mapping is limited because of low
      conductivity of a skull. Cortical dipole layer imaging has been proposed as a
      method to visualize brain electrical activity with high spatial resolution.
      According to this method, about 100 electrodes were required to measure whole
      brain electrical activity. In the present study, we investigated simplified
      cortical dipole imaging with a small number of electrodes. The density of
      electrodes and the spatial resolution are in a trade-off relation. Thus, the
      number of electrodes was reduced by limiting the visualization region of
      interest, without lowering the density of electrodes. Moreover, independent
      component analysis was applied to the multiple signal sources to extract an
      attention signal from the other signals and noise. In simulation, even if the
      number of electrodes was reduced to 25, the obtained results were almost
      equivalent to the case with whole brain electrodes. The proposed method was
      applied to human experimental data of movement-related potential. We confirmed
      that the proposed method provided high resolution cortical dipole imaging with
      localized distribution. 

PMID- 25571100
TI  - Motor task-based differences in brain networks: preliminary results.
AB  - This study examined characteristics of the brain networks related to upper limb
      grasp movements. EEG signal of 4 patients with chronic stroke were analyzed
      during different motor tasks. We compared the brain networks involved in the
      Active and Motor Imagery tasks by using the centrality and small-worldness (SW).
      There was a statistically significant difference between the centralities of two
      motor tasks in motor cortices of affected hemisphere in the high beta band (21-30
      Hz). For SW, the Active task also decreased in the high beta band in contrast
      with the MI task. In this paper, we could support evidence that brain networks
      may different under the conditions of different motor tasks in both frequency and
      temporal domain. 

PMID- 25571101
TI  - Predicting occurrence of errors during a Go/No-Go task from EEG signals using
      Support Vector Machine.
AB  - Human error often becomes a serious problem in dairy life. Recent studies have
      shown that failures of attention and motor errors can be captured before they
      actually occur in the alpha, theta, and beta-band powers of electroencephalograms
      (EEGs), suggesting the possibility that errors in motor responses can be
      predicted. The goal of this study was to use single-trial offline classification
      to examine how accurately EEG signals recorded before motor responses can predict
      subsequent errors. Ten subjects performed a Go/No-Go task, and the accuracy of
      error classification by a Support Vector Machine (SVM) was investigated 1000 ms
      before presenting the Go/No-Go cue. The resulting mean classification accuracy
      was 62%, and strong increases and decreases in activities associated with errors
      were observed in occipital and frontal alpha-band powers. This result suggests
      the possibility that future errors can be predicted using EEG. 

PMID- 25571102
TI  - Mental rotation process for mirrored and identical stimuli: a beta-band ERD
      study.
AB  - This study investigated mental rotation for identical stimuli and mirrored
      stimuli by both behavior response and event-related desynchronization (ERD) of
      EEG signals. Results showed that subjects had longer response time for mirrored
      stimuli than identical stimuli. Beta-band desynchronization appeared in whole
      brain with the parietal-occipital dominance. The ERD in beta band recovered
      slowly in an angular order after 450-600 ms of stimulus onset except the sharp
      rebound in the case of identical stimuli with rotation at 0  degrees . This
      temporal difference of beta ERD between the identical and the mirrored stimuli at
      0 degrees  rotation and the ERD topographic difference in left fronto-parietal
      regions, together with the behavior difference, may imply an extra flip process
      in mirrored condition. 

PMID- 25571103
TI  - Design of an fMRI-compatible optical touch stripe based on frustrated total
      internal reflection.
AB  - Previously we developed a low-cost, multi-configurable handheld response system,
      using a reflective-type intensity modulated fiber-optic sensor (FOS) to
      accurately gather participants' behavioral responses during functional magnetic
      resonance imaging (fMRI). Inspired by the popularity and omnipresence of the
      fingertip-based touch sensing user interface devices, in this paper we present
      the design of a prototype fMRI-compatible optical touch stripe (OTS) as an
      alternative configuration. The prototype device takes advantage of a proven
      frustrated total internal reflection (FTIR) technique. By using a custom-built
      wedge-shaped optically transparent acrylic prism as an optical waveguide, and a
      plano-concave lens to provide the required light beam profile, the position of a
      fingertip touching the surface of the wedge prism can be determined from the
      deflected light beams that become trapped within the prism by total internal
      reflection. To achieve maximum sensitivity, the optical design of the wedge prism
      and lens were optimized through a series of light beam simulations using WinLens
      3D Basic software suite. Furthermore, OTS performance and MRI-compatibility were
      assessed on a 3.0 Tesla MRI scanner running echo planar imaging (EPI) sequences.
      The results show that the OTS can detect a touch signal at high spatial
      resolution (about 0.5 cm), and is well suited for use within the MRI environment
      with average time-variant signal-to-noise ratio (tSNR) loss < 3%.

PMID- 25571104
TI  - Assessing the privacy policies in mobile personal health records.
AB  - The huge increase in the number and use of smartphones and tablets has led health
      service providers to take an interest in mHealth. Popular mobile app markets like
      Apple App Store or Google Play contain thousands of health applications. Although
      mobile personal health records (mPHRs) have a number of benefits, important
      challenges appear in the form of adoption barriers. Security and privacy have
      been identified as part of these barriers and should be addressed. This paper
      analyzes and assesses a total of 24 free mPHRs for Android and iOS.
      Characteristics regarding privacy and security were extracted from the HIPAA. The
      results show important differences in both the mPHRs and the characteristics
      analyzed. A questionnaire containing six questions concerning privacy policies
      was defined. Our questionnaire may assist developers and stakeholders to evaluate
      the security and privacy of their mPHRs. 

PMID- 25571105
TI  - Validity of association rules extracted by healthcare-data-mining.
AB  - A personal healthcare system used with cloud computing has been developed. It
      enables a daily time-series of personal health and lifestyle data to be stored in
      the cloud through mobile devices. The cloud automatically extracts personally
      useful information, such as rules and patterns concerning the user's lifestyle
      and health condition embedded in their personal big data, by using healthcare
      data-mining. This study has verified that the extracted rules on the basis of a
      daily time-series data stored during a half- year by volunteer users of this
      system are valid.

PMID- 25571106
TI  - Unobtrusive monitoring of ECG-derived features during daily smartphone use.
AB  - Heart rate variability (HRV) is known to be one of the representative ECG-derived
      features that are useful for diverse pervasive healthcare applications. The
      advancement in daily physiological monitoring technology is enabling monitoring
      of HRV in people's everyday lives. In this study, we evaluate the feasibility of
      measuring ECG-derived features such as HRV, only using the smartphone-integrated
      ECG sensors system named Sinabro. We conducted the evaluation with 13 subjects in
      five predetermined smartphone use cases. The result shows the potential that the
      smartphone-based sensing system can support daily monitoring of ECG-derived
      features; The average errors of HRV over all participants ranged from 1.65% to
      5.83% (SD: 2.54~10.87) for five use cases. Also, all of individual HRV parameters
      showed less than 5% of average errors for the three reliable cases. 

PMID- 25571107
TI  - A real time study of the human equilibrium using an instrumented insole with 3
      pressure sensors.
AB  - The present work deals with the study of the human equilibrium using an
      ambulatory e-health system. One of the point on which we focus is the fall risk,
      when losing equilibrium control. A specific postural learning model is presented,
      and an ambulatory instrumented insole is developed using 3 pressures sensors per
      foot, in order to determine the real-time displacement and the velocity of the
      centre of pressure (CoP). The increase of these parameters signals a loss of
      physiological sensation, usually of vision or of the inner ear. The results are
      compared to those obtained from classical more complex systems. 

PMID- 25571108
TI  - Analysis of actigraph parameters for relapse prediction in bipolar disorder: a
      feasibility study.
AB  - The paper presents a framework for early identification of prodromal syndromes od
      mania or depression in bipolar disorder. The framework may mitigate relapses and
      improve patient functioning. The methodology consists of long-term actigraphy
      monitoring and simplified self-assessment tool to determine manic or depression
      events. Eight patients were involved in the feasibility study, spanning period of
      150 months, resulting in 17 relapses and 3 hospitalizations in total. We
      concluded that the most promising parameter extracted from actigraphy recording
      is a circadian rhythm's interdaily stability. Using developed trend analysis
      applied on interdaily stability parameter, we achieved sensitivity and
      specificity about 65, resp. 68. We hypothesized that this performance is both
      mainly due to missing values in data and due to small amount of relapses. 

PMID- 25571109
TI  - Physical activity recognition based on rotated acceleration data using quaternion
      in sedentary behavior: a preliminary study.
AB  - This paper suggests a physical activity assessment method based on quaternion. To
      reduce user inconvenience, we measured the activity using a mobile device which
      is not put on fixed position. Recognized results were verified with various
      machine learning algorithms, such as neural network (multilayer perceptron),
      decision tree (J48), SVM (support vector machine) and naive bayes classifier. All
      algorithms have shown over 97% accuracy including decision tree (J48), which
      recognized the activity with 98.35% accuracy. As a result, physical activity
      assessment method based on rotated acceleration using quaternion can classify
      sedentary behavior with more accuracy without considering devices' position and
      orientation. 

PMID- 25571110
TI  - Comparative assessment of sleep quality estimates using home monitoring
      technology.
AB  - Poor sleep quality is associated with chronic diseases, weight increase and
      cognitive dysfunction. Home monitoring solutions offer the possibility of
      offering tailored sleep coaching interventions. There are several new
      commercially available devices for tracking sleep, and although they have been
      tested in sleep laboratories, little is known about the errors associated with
      the use in the home. To address this issue we performed a study in which we
      compared the sleep monitoring data from two commercially available systems:
      Fitbit One and Beddit Pro. We studied 23 subjects using both systems over a week
      each and analyzed the degree of agreement for different aspects of sleep. The
      results suggest the need for individual-tailoring of the estimation process. Not
      only do these models address improved accuracy of sleep quality estimates, but
      they also provide a framework for the representation and harmonization for
      monitoring data across studies. 

PMID- 25571111
TI  - A medication adherence monitoring system for pill bottles based on a wearable
      inertial sensor.
AB  - This paper presents a medication adherence monitoring system for pill bottles
      based on a wearable inertial sensor. Signal templates corresponding to the two
      actions of twist-cap and hand-to-mouth are created using a camera-assisted
      training phase. The act of pill intake is then identified by performing a moving
      window dynamic time warping in real-time between signal templates and the signals
      acquired by the wearable inertial sensor. The outcomes of the experimentations
      carried out indicate that the developed medical adherence monitoring system
      identifies the act of pill intake with a high degree of accuracy. 

PMID- 25571112
TI  - Single-phase dielectrophoretic and electrorotation studies using three
      dimensional electrodes for cell characterization.
AB  - A novel electrokinetic approach using single-phase electrorotation for the label
      free manipulation and characterization of biological cells is presented. A single
      shell model was used to theoretically design and develop an experimental strategy
      for biological particle characterization. As a study model, electro-rotation of
      glutathione agarose (GA) beads was studied using three-dimensional spatially
      oriented micro-needle setup. Effect of electrical parameters (i) voltage: from 0
      10 Vpp and (ii) frequency: 0-100 MHz was evaluated on a heterogeneous mixture of
      GA beads (35-150 microns). The relationship of the electrical parameters to
      rotational frequency of the beads was studied. This paper demonstrates a simple
      and easy to implement prototype for electrokinetic characterization of particles
      with translational potential for biological cells.

PMID- 25571113
TI  - Calibration of a 3D endoscopic system based on active stereo method for shape
      measurement of biological tissues and specimen.
AB  - For endoscopic medical treatment, measuring the size and shape of the lesion,
      such as a tumor, is important for the improvement of diagnostic accuracy. We are
      developing a system to measure the shapes and sizes of living tissue by active
      stereo method using a normal endoscope on which a micro pattern projector is
      attached. In order to perform 3D reconstruction, estimating the intrinsic and
      extrinsic parameters of the endoscopic camera and the pattern projector is
      required. Particularly, calibration of the pattern projector is difficult. In
      this paper, we propose a simultaneous estimation method of both intrinsic and
      extrinsic parameters of the pattern projector. This simplifies the calibration
      procedure required in practical scenes. Furthermore, we have developed an
      efficient user interface to intuitively operate the calibration and
      reconstruction procedures. Using the developed system, we measured the shape of
      an internal tissue of the soft palate of a human and a biological specimen. 

PMID- 25571114
TI  - Modelling and design of a capacitive touch sensor for urinary tract infection
      detection at the point-of-care.
AB  - Due to great use of touchscreens in mobile telephones and other electronic
      devices, there has been great evolution in this technology. Its wide
      applicability makes the touch sensor technology suitable for detection of
      specific components in urine, responsible for urinary tract infection (UTI).
      Integration of a touch sensor in a disposable probe tip to be used in UTI
      detection represents a powerful tool to develop new point-of-care testing (POCT)
      devices. The simplified structure of an electrodes array touch screen was
      simulated using the software COMSOL Multiphysics to prove that capacitive based
      touch screens can be used for detection of UTI. Besides we assumed presence of
      E.coli, one of the major causes of UTI urine. Results show that global
      capacitance increases if an E.coli sphere is present near the active electrodes,
      remaining approximately constant when further apart electrodes are excited. The
      output simulated voltage varies according to the capacitance value, decreasing
      when the capacitance is increased. 

PMID- 25571115
TI  - Three-dimensional super-wideband micro-antenna for high-resolution millimeter
      wave medical imaging.
AB  - This paper reports on a novel super-wideband micro-hemispherical antenna with
      application in millimeter-wave medical imaging. The antenna is composed of a
      hemispherical shell suspended above a substrate and can be fabricated using a
      fabrication technology originally developed for micron-scale electromechanical
      resonators. The antenna exhibits a wide fractional bandwidth of more than 80%
      (from 64 GHz to 150 GHz) and a high gain of 8.6 dBi at its center frequency.
      Radiation parameters of the antenna are characterized and the effect of its super
      wideband behavior on pulsed millimeter-wave imaging is demonstrated. Finally, a
      preliminary array configuration composed of two antennas placed side-by-side in
      the vicinity of a skin-mimicking target is evaluated and the ability to fully
      detect the target has been demonstrated. 

PMID- 25571116
TI  - Analysis of dual-task elderly gait using wearable plantar-pressure insoles and
      accelerometer.
AB  - Dual-task gait allows assessment of impaired executive function and mobility
      control in older individuals, which are risk factors of falls. This study
      investigated gait changes in older individuals due to the addition of a cognitive
      load, using wearable pressure-sensing insole and tri-axial accelerometer
      measures. These wearable sensors can be applied at the point-of-care. Eleven
      elderly (65 years or older) individuals walked 7.62 m with and without a verbal
      fluency cognitive load task while wearing FScan 3000E pressure-sensing insoles in
      both shoes and a Gulf Coast X16-1C tri-axial accelerometer at the pelvis. Plantar
      pressure derived parameters included center of force (CoF) path and temporal
      measures. Acceleration derived measures were descriptive statistics, Fast Fourier
      Transform quartile, ratio of even-to-odd harmonics, and maximum Lyapunov
      exponent. Stride time, stance time, and swing time all significantly increased
      during dual-task compared to single-task walking. Minimum, mean, and median CoF
      stance velocity; cadence; and vertical, anterior-posterior, and medial-lateral
      harmonic ratio all significantly decreased during dual-task walking. Wearable
      plantar pressure-sensing insole and lower back accelerometer derived-measures can
      identify gait differences between single-task and dual-task walking in older
      individuals and could be used in point-of-care environments to assess for
      deficits in executive function and mobility impairments. 

PMID- 25571117
TI  - A novel biphasic-current-pulse calibration technique for electrical neural
      stimulation.
AB  - One of the major challenge in neural prosthetic device design is to ensure charge
      balanced stimulation. This paper presents a new calibration technique to minimize
      the mismatch between anodic and cathodic current amplitudes. The proposed circuit
      mainly consists of a digital and an analog calibration, where a successive
      approximation register (SAR) logic and a comparator are used in digital
      calibration while a source follower is adopted in analog calibration. With a 0.18
      MUm high voltage CMOS process, the simulation shows that the maximum current
      mismatch is 45 nA (<0.05%).

PMID- 25571118
TI  - A multichannel current stimulator chip for spatiotemporal pattern stimulation of
      neural tissues.
AB  - We developed a prototype very-large-scale integration chip of a multichannel
      current stimulator for stimulating neural tissues by utilizing 0.25 MUm high
      voltage complementary metal-oxide-semiconductor technology. Our designed chip has
      20 output channels that are driven by five current buffers arranged in parallel;
      each buffer controls four output channels in time-sharing mode. The amplitude of
      a stimulation pulse can be controlled within a range of approximately +/-100
      MUA/phase in each output channel. The stimulus parameters, e.g., amplitude and
      duration, are controlled separately for each channel by digital codes stored in
      built-in registers. Combinations of anode and cathode electrodes to pass the
      current can be changed online. We integrated our stimulator chip with a
      multielectrode array and studied the neuronal responses to multichannel current
      stimulations with various temporal patterns in mouse brain slices. 

PMID- 25571119
TI  - System-in-package solution for a low-power active electrode module.
AB  - This paper presents the design of system in package for a low-power active
      electrode module. The main aim of this research is to provide a low-cost, high
      density, and high-quality module, exploiting the features of a System-in-Package
      (SiP) solution. To the best knowledge of the authors, this is the first time that
      SiP technology has been used in the development of a modular active electrode.
      Two SiPs have been designed and one of them has been fabricated and tested. The
      dimensions of the latter are 7*7*1 mm and it was designed taking in account the
      necessity of soldering it by hand. On the contrary, the other package dimensions
      are 4.5*4.5*1 mm and it was designed for fully exploiting the latest technologies
      available to authors. The SiPs have been designed to be reused in different
      electrocardiogram (ECG) systems and are easy to solder using ball grids arrays
      (BGA) and land grids arrays (LGA) as second level interconnection; both these
      features allow to reduce the time to market of the supra-system including the
      module. The active electrode presents a bandwidth which ranges from 7.9 mHz to
      300 Hz and it has a mid-band gain which can be set to a maximum value of 40 dB.
      The fabricated SiP has been tested on a printed circuit board (PCB), with an
      input signal generated by a Dimetek iBUSS-P biomedical signal simulator showing a
      satisfying functioning of the SiP.

PMID- 25571120
TI  - Analytical model for real time, noninvasive estimation of blood glucose level.
AB  - The paper presents an analytical model to estimate blood glucose level from
      measurements made non-invasively and in real time by an antenna strapped to a
      patient's wrist. Some promising success has been shown by the RIT ETA Lab
      research group that an antenna's resonant frequency can track, in real time,
      changes in glucose concentration. Based on an in-vitro study of blood samples of
      diabetic patients, the paper presents a modified Cole-Cole model that
      incorporates a factor to represent the change in glucose level. A calibration
      technique using the input impedance technique is discussed and the results show a
      good estimation as compared to the glucose meter readings. An alternate
      calibration methodology has been developed that is based on the shift in the
      antenna resonant frequency using an equivalent circuit model containing a shunt
      capacitor to represent the shift in resonant frequency with changing glucose
      levels. Work under progress is the optimization of the technique with a larger
      sample of patients. 

PMID- 25571121
TI  - Evaluating the use of line length for automatic sleep spindle detection.
AB  - Sleep spindles are transient waveforms observed on the electroencephalogram (EEG)
      during the N2 stage of sleep. In this paper we evaluate the use of line length,
      an efficient and low-complexity time domain feature, for automatic detection of
      sleep spindles. We use this feature with a simple algorithm to detect spindles
      achieving sensitivity of 83.6% and specificity of 87.9%. We also present a
      comparison of these results with other spindle detection methods evaluated on the
      same dataset. Further, we implemented the algorithm on a MSP430 microcontroller
      achieving a power consumption of 56.7 MUW. The overall detection performance,
      combined with the low power consumption show that line length could be a useful
      feature for detecting sleep spindles in wearable and resource-constrained
      systems. 

PMID- 25571122
TI  - Naive scoring of human sleep based on a hidden Markov model of the
      electroencephalogram.
AB  - Clinical sleep scoring involves tedious visual review of overnight polysomnograms
      by a human expert. Many attempts have been made to automate the process by
      training computer algorithms such as support vector machines and hidden Markov
      models (HMMs) to replicate human scoring. Such supervised classifiers are
      typically trained on scored data and then validated on scored out-of-sample data.
      Here we describe a methodology based on HMMs for scoring an overnight sleep
      recording without the benefit of a trained initial model. The number of states in
      the data is not known a priori and is optimized using a Bayes information
      criterion. When tested on a 22-subject database, this unsupervised classifier
      agreed well with human scores (mean of Cohen's kappa > 0.7). The HMM also
      outperformed other unsupervised classifiers (Gaussian mixture models, k-means,
      and linkage trees), that are capable of naive classification but do not model
      dynamics, by a significant margin (p < 0.05).

PMID- 25571123
TI  - Performance analysis of a Principal Component Analysis ensemble classifier for
      Emotiv headset P300 spellers.
AB  - The current trend to use Brain-Computer Interfaces (BCIs) with mobile devices
      mandates the development of efficient EEG data processing methods. In this paper,
      we demonstrate the performance of a Principal Component Analysis (PCA) ensemble
      classifier for P300-based spellers. We recorded EEG data from multiple subjects
      using the Emotiv neuroheadset in the context of a classical oddball P300 speller
      paradigm. We compare the performance of the proposed ensemble classifier to the
      performance of traditional feature extraction and classifier methods. Our results
      demonstrate the capability of the PCA ensemble classifier to classify P300 data
      recorded using the Emotiv neuroheadset with an average accuracy of 86.29% on
      cross-validation data. In addition, offline testing of the recorded data reveals
      an average classification accuracy of 73.3% that is significantly higher than
      that achieved using traditional methods. Finally, we demonstrate the effect of
      the parameters of the P300 speller paradigm on the performance of the method. 

PMID- 25571124
TI  - Classification of borderline personality disorder based on spectral power of
      resting-state fMRI.
AB  - Borderline personality disorder (BPD) is a serious mental illness that can cause
      significant suffering and carries a risk of suicide. Assigning an accurate
      diagnosis is critical to guide treatment. Currently, the diagnosis of BPD is made
      exclusively through the use of clinical assessment; no objective test is
      available to assist with its diagnosis. Thus, it is highly desirable to explore
      quantitative biomarkers to better characterize this illness. In this study, we
      extract spectral power features from the power spectral density and cross
      spectral density of resting-state fMRI data, covering 20 brain regions and 5
      frequency bands. Machine learning approaches are employed to select the most
      discriminating features to identify BPD. Following a leave-one-out cross
      validation procedure, the proposed approach achieves 93.55% accuracy (100%
      specificity and 90.48% sensitivity) in classifying 21 BPD patients from 10
      healthy controls based on the top ranked features. The most discriminating
      features are selected from the 0.1~0.15 Hz frequency band, and are located at the
      left medial orbitofrontal cortex, the left thalamus, and the right rostral
      anterior cingulate cortex. The high classification accuracy indicates the
      discriminating power of the spectral power features in BPD identification. The
      proposed machine learning approach may be used as an objective test to assist
      clinical diagnosis of BPD.

PMID- 25571125
TI  - Multimodal emotion recognition using EEG and eye tracking data.
AB  - This paper presents a new emotion recognition method which combines
      electroencephalograph (EEG) signals and pupillary response collected from eye
      tracker. We select 15 emotional film clips of 3 categories (positive, neutral and
      negative). The EEG signals and eye tracking data of five participants are
      recorded, simultaneously, while watching these videos. We extract emotion
      relevant features from EEG signals and eye tracing data of 12 experiments and
      build a fusion model to improve the performance of emotion recognition. The best
      average accuracies based on EEG signals and eye tracking data are 71.77% and
      58.90%, respectively. We also achieve average accuracies of 73.59% and 72.98% for
      feature level fusion strategy and decision level fusion strategy, respectively.
      These results show that both feature level fusion and decision level fusion
      combining EEG signals and eye tracking data can improve the performance of
      emotion recognition model. 

PMID- 25571126
TI  - Recommendations for performance assessment of automatic sleep staging algorithms.
AB  - A number of automatic sleep scoring algorithms have been published in the last
      few years. These can potentially help save time and reduce costs in sleep
      monitoring. However, the use of both R&K and AASM classification, different
      databases and varying performance metrics makes it extremely difficult to compare
      these algorithms. In this paper, we describe some readily available
      polysomnography databases and propose a set of recommendations and performance
      metrics to promote uniform testing and direct comparison of different algorithms.
      We use two different polysomnography databases with a simple sleep staging
      algorithm to demonstrate the usage of all recommendations and presentation of
      performance results. We also illustrate how seemingly similar results using two
      different databases can have contrasting accuracies in different sleep stages.
      Finally, we show how selection of different training and test subjects from the
      same database can alter the final performance results. 

PMID- 25571127
TI  - Adaptive coherent averaging for real-time electrocardiogram enhancement.
AB  - This paper presents an adaptive coherent averaging structure capable of removing
      broad-band interference from the electrocardiogram (ECG) while preserving the
      morphological features of the signal. The proposed structure improves the signal
      to-noise ratio (SNR) of the adaptive line enhancer (ALE) while maintaining
      robustness to quasi-periodic signals. The least mean-square (LMS) and recursive
      least-square (RLS) adaptive algorithms are implemented. Analysis and comparison
      of the results is provided, leading to an optimized hybrid implementation. The
      cascade nature of the proposed structure is both scalable and suitable for
      implementation in real-time hardware. 

PMID- 25571128
TI  - Bounded-observation Kalman filtering of correlation in multivariate neural
      recordings.
AB  - A persistent question in multivariate neural signal processing is how best to
      characterize the statistical association between brain regions known as
      functional connectivity. Of the many metrics available for determining such
      association, the standard Pearson correlation coefficient (i.e., the zero-lag
      cross-correlation) remains widely used, particularly in neuroimaging. Generally,
      the cross-correlation is computed over an entire trial or recording session, with
      the assumption of within-trial stationarity. Increasingly, however, the length
      and complexity of neural data requires characterizing transient effects and/or
      non-stationarity in the temporal evolution of the correlation. That is, to
      estimate dynamics in the association between brain regions. Here, we present a
      simple, data-driven Kalman filter-based approach to tracking correlation
      dynamics. The filter explicitly accounts for the bounded nature of correlation
      measurements through the inclusion of a Fisher transform in the measurement
      equation. An output linearization facilitates a straightforward implementation of
      the standard recursive filter equations, including admittance of covariance
      identification via an autoregressive least squares method. We demonstrate the
      efficacy and utility of the approach in an example of multivariate neural
      functional magnetic resonance imaging data. 

PMID- 25571129
TI  - Automatic selection of optimal Savitzky-Golay filter parameters for Coronary Wave
      Intensity Analysis.
AB  - Coronary Wave Intensity Analysis (cWIA) is a technique capable of separating the
      effects of proximal arterial haemodynamics from cardiac mechanics. The cWIA
      ability to establish a mechanistic link between coronary haemodynamics
      measurements and the underlying pathophysiology has been widely demonstrated.
      Moreover, the prognostic value of a cWIA-derived metric has been recently proved.
      However, the clinical application of cWIA has been hindered due to the strong
      dependence on the practitioners, mainly ascribable to the cWIA-derived indices
      sensitivity to the pre-processing parameters. Specifically, as recently
      demonstrated, the cWIA-derived metrics are strongly sensitive to the Savitzky
      Golay (S-G) filter, typically used to smooth the acquired traces. This is mainly
      due to the inability of the S-G filter to deal with the different timescale
      features present in the measured waveforms. Therefore, we propose to apply an
      adaptive S-G algorithm that automatically selects pointwise the optimal filter
      parameters. The newly proposed algorithm accuracy is assessed against a cWIA gold
      standard, provided by a newly developed in-silico cWIA modelling framework, when
      physiological noise is added to the simulated traces. The adaptive S-G algorithm,
      when used to automatically select the polynomial degree of the S-G filter,
      provides satisfactory results with <= 10% error for all the metrics through all
      the levels of noise tested. Therefore, the newly proposed method makes cWIA fully
      automatic and independent from the practitioners, opening the possibility to
      multi-centre trials. 

PMID- 25571131
TI  - The impact of head movements on EEG and contact impedance: an adaptive filtering
      solution for motion artifact reduction.
AB  - Designing and developing a comfortable and convenient EEG system for daily usage
      that can provide reliable and robust EEG signal, encompasses a number of
      challenges. Among them, the most ambitious is the reduction of artifacts due to
      body movements. This paper studies the effect of head movement artifacts on the
      EEG signal and on the dry electrode-tissue impedance (ETI), monitored
      continuously using the imec's wireless EEG headset. We have shown that motion
      artifacts have huge impact on the EEG spectral content in the frequency range
      lower than 20 Hz. Coherence and spectral analysis revealed that ETI is not
      capable of describing disturbances at very low frequencies (below 2 Hz).
      Therefore, we devised a motion artifact reduction (MAR) method that uses a
      combination of a band-pass filtering and multi-channel adaptive filtering (AF),
      suitable for real-time MAR. This method was capable of substantially reducing
      artifacts produced by head movements.

PMID- 25571130
TI  - Multi-kinect skeleton fusion for physical rehabilitation monitoring.
AB  - Kinect has been increasingly applied in rehabilitation as a motion capture
      device. However, the inherent limitations significantly hinder its further
      development in this important area. Although a number of Kinect fusion approaches
      have been proposed, only a few of them was actually considered for
      rehabilitation. In this paper, we propose to fuse information from multiple
      Kinects to achieve this. Given the specific scenario of users suffering from
      limited range of movements, we propose to calibrate depth cameras in multiple
      Kinects with 3D positions of joints on a human body rather than in a checkerboard
      pattern, so that patients are able to calibrate Kinects without extra support.
      Kalman filter is applied for skeleton-wise Kinect fusion since skeleton data (3D
      positions of joints) and its derivatives are preferred by physiotherapists to
      evaluate the exercise performance of patients. Various preliminary experiments
      were conducted to illustrate the accuracy of proposed calibration and fusion
      approach by comparing with a commercial Vicon system(r), confirming the practical
      use of the system in rehabilitation exercise monitoring. 

PMID- 25571132
TI  - Continuous motion decoding from EMG using independent component analysis and
      adaptive model training.
AB  - Surface Electromyography (EMG) is popularly used to decode human motion intention
      for robot movement control. Traditional motion decoding method uses pattern
      recognition to provide binary control command which can only move the robot as
      predefined limited patterns. In this work, we proposed a motion decoding method
      which can accurately estimate 3-dimensional (3-D) continuous upper limb motion
      only from multi-channel EMG signals. In order to prevent the muscle activities
      from motion artifacts and muscle crosstalk which especially obviously exist in
      upper limb motion, the independent component analysis (ICA) was applied to
      extract the independent source EMG signals. The motion data was also transferred
      from 4-manifold to 2-manifold by the principle component analysis (PCA). A hidden
      Markov model (HMM) was proposed to decode the motion from the EMG signals after
      the model trained by an adaptive model identification process. Experimental data
      were used to train the decoding model and validate the motion decoding
      performance. By comparing the decoded motion with the measured motion, it is
      found that the proposed motion decoding strategy was feasible to decode 3-D
      continuous motion from EMG signals. 

PMID- 25571133
TI  - The effect of acute coronary perfusion change on cardiac function measured by
      Shear Wave Elasticity Imaging.
AB  - The possibility of measuring cardiac function noninvasively has generated wide
      interest in elastography imaging techniques. Shear Wave Elasticity Imaging (SWEI)
      is an ultrasound-based elastography technique used to measure stiffness of
      tissues. While this technique has been studied extensively in static homogenous
      tissues such as liver, breast or prostate, there is still a significant need to
      study its capabilities to measure cardiac stiffness and function. In this
      research, we have studied the potential of SWEI to evaluate the coronary
      perfusion pressure effect on systolic and diastolic stiffness referred to as
      elastance and compliance of the heart. Five isolated rabbit hearts were used in
      this study in a Langendorff preparation. SWEI measurements of stiffness were
      recorded in two steps. In the first step, coronary perfusion was set to normal
      and then was reduced to half-normal. After 40 minutes of half-normal perfusion,
      it was returned to normal perfusion for the second step. SWEI velocity decreased
      from 6.003 m/s to 4.713 m/s in systole and from 1.948 m/s to 1.507 m/s in
      diastole in the first step. During the second step raising the perfusion to
      normal, SWEI stiffness showed an increase from 3.760 m/s to 5.468 m/s in systole
      and from 1.678 m/s to 2.156 m/s during diastole. Our results show that SWEI
      measurements of stiffness can characterize the cross talk between coronary
      perfusion and cardiac stiffness and also has the potential to measure compliance
      and elastance of the heart in systole and diastole. 

PMID- 25571135
TI  - Toward a reduced-wire readout system for ultrasound imaging.
AB  - We present a system-on-a-chip (SoC) for use in high-frequency capacitive
      micromachined ultrasonic transducer (CMUT) imaging systems. This SoC consists of
      trans-impedance amplifiers (TIA), delay locked loop (DLL) based clock multiplier,
      quadrature sampler, and pulse width modulator (PWM). The SoC down converts RF
      echo signal to baseband by quadrature sampling which facilitates modulation. To
      send data through a 1.6 m wire in the catheter which has limited bandwidth and is
      vulnerable to noise, the SoC creates a pseudo-digital PWM signal which can be
      used for back telemetry or wireless readout of the RF data. In this
      implementation, using a 0.35-MUm std. CMOS process, the TIA and single-to
      differential (STD) converter had 45 MHz bandwidth, the quadrature sampler had
      10.1 dB conversion gain, and the PWM had 5-bit ENoB. Preliminary results verified
      front-end functionality, and the power consumption of a TIA, STD, quadrature
      sampler, PWM, and clock multiplier was 26 mW from a 3 V supply. 

PMID- 25571134
TI  - Automatic dissociation between microvasculature and larger vessels for ultrasound
      contrast imaging.
AB  - Microvasculature density (MVD) provides an established biomarker for the
      prognosis of numerous diseases associated with abnormal microvascular networks.
      The accurate, robust and timely assessment of MVD changes facilitates disease
      detection, treatment monitoring and patient stratification. Nevertheless, the
      current gold standard (PET) for MVD quantification is not used in clinical
      practice due to its high costs and potential health hazards. Contrast Enhanced
      Ultrasound (CEUS) imaging can provide an attractive alternative. However, the
      limited dissociation between larger vessels and microvasculature in the imaged
      tissues limits the accuracy and robustness of CEUS. This study proposed a novel,
      and fully automatic technique that dissociates larger vessels from
      microvasculature in CEUS imaged tissues. The ovine Corpus Luteum (CL) was used as
      an in vivo model for the development and assessment of the proposed technique. 

PMID- 25571136
TI  - Stabilization technique for real-time high-resolution vascular ultrasound using
      frequency domain interferometry.
AB  - We have proposed an ultrasound imaging method based on frequency domain
      interferometry (FDI) with an adaptive beamforming technique to depict real-time
      high-resolution images of human carotid artery. Our previous study has
      investigated the performance of the proposed imaging method under an ideal
      condition with a high signal-to-noise ratio (SNR). In the present study, we
      propose a technique that has the potential to improve accuracy in estimating echo
      intensity using the FDI imaging method. We investigated the performance of the
      proposed technique in a simulation study that two flat interfaces were located at
      depths of 15.0 and 15.2 mm and white noise was added. Because the -6 dB bandwidth
      of the signal used in this simulation study is 2.6 MHz, the conventional B-mode
      imaging method failed to depict the two interfaces. Both the conventional and
      proposed FDI imaging methods succeeded to depict the two interfaces when the SNR
      ranged from 15 to 30 dB. However, the average error of the estimated echo
      intensity at the interfaces using the conventional FDI imaging method ranged from
      7.2 to 10.5 dB. In contrast, that using the FDI imaging method with the proposed
      technique ranged from 2.0 to 2.2 dB. The present study demonstrates the potential
      of the FDI imaging method in depicting robust and high-range-resolution
      ultrasound images of arterial wall, indicating the possibility to improve the
      diagnosis of atherosclerosis in early stages. 

PMID- 25571137
TI  - Automatic carotid centerline extraction from three-dimensional ultrasound Doppler
      images.
AB  - Vessel lumen centerline extraction is an important issue for the intra-operative
      guidance of endovascular instruments; furthermore, vessel centerline is often
      used as a reference position in many hemodynamic studies, especially in carotid
      arteries. In this work we propose an innovative method for the extraction of
      carotid vessels centerline from three-dimensional Color Doppler ultrasound
      images. The method was tested on carotid Color Doppler images of eighteen healthy
      subjects and validated by calculating the Euclidean distances between the
      centerlines detected by the algorithm and those manually annotated by two experts
      in the corresponding original US volumes. The results show that the proposed
      approach can accurately estimate the actual centerline with an average error of
      1.08 +/- 0.54 mm. Furthermore, the method is completely automatic and therefore
      suitable for the aforementioned purposes. 

PMID- 25571138
TI  - Two-dimensional blood flow vectors obtained with bidirectional Doppler
      ultrasound.
AB  - Precise measurement of blood flow is important because blood flow closely
      correlates formation of thrombus and atherosclerotic plaque. Among clinically
      applied modalities for blood flow measurement, color Doppler ultrasound shows two
      dimensional (2D) distribution of one-dimensional blood flow component along the
      ultrasound beam. In the present study, 2D blood flow vector is obtained with high
      temporal and bidirectional Doppler ultrasound technique. Linear array probe with
      the central frequency of 7.5 MHz and an ultrasound data acquisition system with
      128 transmit and 128 receive channels were equipped. Frame rate of 5 kHz was
      achieved by parallel receive beam forming with a wide transmitted wave. The flow
      velocity was measured from two different angles by beam steering. The interval of
      two measurements was 0.8 msec and it was considered as almost one moment to
      obtain 2D blood flow vector. B-mode image and 2D blood flow vector of the
      pulsatile flow in a carotid artery model showed small vortex at the bifurcation
      area. The method was also applied for visualization of in vivo blood flow vector
      in human carotid arteries. 2D blood flow measurement may predict the risk area of
      thrombus and plaque formation induced by abnormal blood flow. 

PMID- 25571139
TI  - Pressure mapping from flow imaging: enhancing computation of the viscous term
      through velocity reconstruction in near-wall regions.
AB  - Although being small compared to inertial acceleration, viscous component of the
      pressure gradient has recently emerged as a potential biomarker for aortic
      disease conditions including aortic valve stenosis. However, as it involves the
      computation of second order derivatives and viscous dissipation is locally higher
      in the near-wall region of the larger vessels, where the lowest local signal-to
      noise ratios are encountered, the estimation process from medical image velocity
      data through mathematical models is highly challenging. We propose a fully
      automatic framework to recover the laminar viscous pressure gradient through
      reconstruction of the velocity vector field in the aortic boundary region. An in
      silico study is conducted and the pressure drop is computed solving a Poisson
      problem on pressure using both a reconstructed and non-reconstructed velocity
      profile near the vessel walls, showing a global improvement of performance with
      the enhanced method. 

PMID- 25571140
TI  - Estimating dense cardiac 3D motion using sparse 2D tagged MRI cross-sections.
AB  - In this work, we describe a new method, an extension of the Large Deformation
      Diffeomorphic Metric Mapping to estimate three-dimensional deformation of tagged
      Magnetic Resonance Imaging Data. Our approach relies on performing non-rigid
      registration of tag planes that were constructed from set of initial reference
      short axis tag grids to a set of deformed tag curves. We validated our algorithm
      using in-vivo tagged images of normal mice. The mapping allows us to compute root
      mean square distance error between simulated tag curves in a set of long axis
      image planes and the acquired tag curves in the same plane. Average RMS error was
      0.31 +/- 0.36(SD) mm, which is approximately 2.5 voxels, indicating good matching
      accuracy. 

PMID- 25571141
TI  - Pixel-wise absolute pressures in the aortic arch from 3D MRI velocity data and
      carotid artery applanation tonometry.
AB  - A pixel-wise method for absolute and local aortic pressures estimation using 3D
      velocities in MRI and carotid pressure curves to set-up reference pressure values
      is presented. This method is based on the Navier-Stokes equation and a fast
      iterative algorithm. Its reliability was demonstrated: 1) in a synthetic phantom
      by comparison against simplified Bernoulli equation applied at peak velocities,
      and 2) in a healthy subject and a patient with aortic coarctation, in which
      absolute pressure distribution within the aortic arch was consistent with
      established physiopathological knowledge. Such local absolute aortic pressures
      may be useful in the understanding of hemodynamic changes secondary to
      cardiovascular alterations. Also, their addition to the already available indices
      of risk of aortic complications such as dilatation and dissection definition may
      prove of major clinical usefulness. 

PMID- 25571142
TI  - Unconstrained l1-regularized minimization with interpolated transformations for
      heart motion compensation.
AB  - Motion compensation constitutes a challenging issue in minimally invasive beating
      heart surgery. Since the zone to be repaired has a dynamic behaviour, precision
      and surgeon's dexterity decrease. In order to solve this problem, various
      proposals have been presented using l2-norm. However, as they present some
      limitations in terms of robustness and efficiency, motion compensation is still
      considered an open problem. In this work, a solution based on the class of l1
      Regularized Optimization is proposed. It has been selected due to its
      mathematical properties and practical benefits. In particular, deformation is
      characterized by cubic B-splines since they offer an excellent balance between
      computational cost and accuracy. Moreover, due to the non-differentiability of
      the functional, the logarithmic barrier function is used for generating a
      standard optimization problem. Results have provided a very good tradeoff between
      accuracy and efficiency, indicating the potential of the proposed approach and
      proving its stability even under complex deformations. 

PMID- 25571143
TI  - Left ventricular regional shape dynamics analysis by three-dimensional cardiac
      magnetic resonance imaging associated with left ventricular function in first
      time myocardial infarction patients.
AB  - Geometric remodelling of the left ventricle (LV) following myocardial infarction
      reflects on the geometric characteristics directly. This study focuses on a
      potential index based on curvedness. Nine consecutive normal volunteers and
      thirty consecutive myocardial infarction patients underwent MRI scan (twenty
      seven patients had follow-up scan). Short-axis cine images of all cases were
      delineated. Three dimensional LV models were reconstructed and restored for
      possible motion distortion. The curvedness values were computed over 16-segments
      nomenclature. The curvedness signal for each segment over twenty-two time frames
      were fitted using a second order Fourier Series. Fourier coefficients were
      extracted and unsupervised learning was conducted between normal and patient
      data. An accuracy of 89% and adjusted Rand Index of 0.5374 suggest that these
      Fourier Series and curvedness based features can be an useful index for prognosis
      and diagnosis in clinical practice. 

PMID- 25571144
TI  - Automatic synthesis of cine viability MRI images for evaluation of coronary heart
      disease.
AB  - Coronary heart disease (CHD) is the leading cause of death worldwide. Cardiac
      magnetic resonance imaging (MRI) is a valuable imaging modality, as it can
      noninvasively provide information about myocardial function, viability, and
      morphology. Viability delayed-enhancement (DE) images are acquired at a single
      timeframe while myocardial functional (tagged) images are acquired as a cine loop
      of timeframes throughout the cardiac cycle. In this work, we propose a method for
      estimating DE images at all timeframes in the cardiac cycle without additional
      scan time to show both viability and functional information in the same image.
      The method is based on generating a dense motion field of the heart from the
      acquired tagged images, and then applying the extracted field to the acquired DE
      image. The developed technique is accurate in generating cine DE images and
      providing simultaneous information about myocardial viability and wall motion for
      comprehensive patient evaluation and optimal treatment selection. 

PMID- 25571145
TI  - 3D CT to 2D low dose single-plane fluoroscopy registration algorithm for in-vivo
      knee motion analysis.
AB  - A limitation to accurate automatic tracking of knee motion is the noise and
      blurring present in low dose X-ray fluoroscopy images. For more accurate
      tracking, this noise should be reduced while preserving anatomical structures
      such as bone. Noise in low dose X-ray images is generated from different sources,
      however quantum noise is by far the most dominant. In this paper we present an
      accurate multi-modal image registration algorithm which successfully registers 3D
      CT to 2D single plane low dose noisy and blurred fluoroscopy images that are
      captured for healthy knees. The proposed algorithm uses a new registration
      framework including a filtering method to reduce the noise and blurring effect in
      fluoroscopy images. Our experimental results show that the extra pre-filtering
      step included in the proposed approach maintains higher accuracy and
      repeatability for in vivo knee joint motion analysis. 

PMID- 25571146
TI  - Does malpositioning of the arm influence radiographic range of motion
      measurement?
AB  - PURPOSE: Radiographic range of motion measurement of the elbow has been shown to
      be both precise and reliable. For this method to be used routinely in research
      studies, it is important to describe its limits regarding: (1) rotation of the
      arm from the perfect lateral position and (2) the length of humerus and ulna
      visible on the radiograph. MATERIAL AND METHODS: A 3D bone reconstruction was
      performed from an upper limb CT scan. Planar radiographs were simulated for
      rotations of the elbow within a range of +/-30o from the perfect lateral
      position. The field of view was modified, ranging from five visible centimeters
      of diaphysis on the radiograph to full visibility of the upper limb. RESULTS: The
      disparity was less than 2.5 degrees  (mean=0.68 degrees , SD=0.43 degrees ) when
      the flexed arm was rotated between -30.0 degrees  (external rotation, ER) and +
      18.0 degrees  (internal rotation, IR). When considering the extended arm,
      measured angles differed by less than 2.5 degrees  (mean=0.79 degrees , SD=0.57
      degrees ) within a range of -15.0 degrees  (ER) to +30.0 degrees  (IR). When a
      minimum of 12 cm of humerus and ulna, from the capitellum, were visible on the
      radiograph measured angles varied very slightly (mean disparity of 0.71 degrees ,
      SD= 0.71 degrees ). Finally a qualitative description of the appearance of the
      radiographs was included to help surgeons estimate acceptable degrees of
      rotation. CONCLUSION: Range of motion (ROM) measurement shows consistent results,
      despite 15 to 30 degrees of internal or external rotation. The middle third of
      the humeral and ulnar diaphyses should be visible on the radiographs to ensure
      the validity of measurement. Radiographic ROM measurement is still recommended
      over the goniometer for research purposes because of its high reliability and
      precision. Moreover, malpositioning of the elbow should not jeopardize results
      since it will most likely be an angle measurement variation of less than 2.5
      degrees .

PMID- 25571147
TI  - Estimation of liver iron concentration by dual energy CT images: influence of X
      ray energy on sensitivity.
AB  - In hemochromatosis an abnormal accumulation of iron is present in parenchymal
      organs and especially in liver. Among the several techniques employed to diagnose
      the iron overload, magnetic resonance imaging (MRI) and Computed Tomography (CT)
      are the most promising non-invasive ones. MRI is largely used but shows
      limitation including an overestimation of iron and inability to quantify iron at
      very high concentrations. Therefore, some research groups are focusing on the
      estimation of iron concentration by CT images. Single X-ray CTs are not able to
      accurately perform this task in case of the presence of confounding factors
      (e.g., fat). A potential solution to overcome this concern is the employment of
      Dual-Energy CT (DECT). The aim of this work is to investigate influence of the
      kVp and mAs on CT number sensitivity to iron concentration. A phantom with test
      tubes filled with homogenized porcine liver at different iron concentrations, has
      been scanned with DECT at different mAs. The images have been analyzed using an
      ad-hoc developed algorithm which allows minimizing the influence of air bubbles
      present in the homogenized. Data show that the sensitivity is strongly influenced
      by kVp (its value almost halves from 80 kVp to 140 kVp; e.g. 0.41 g.MUmol(-1) and
      0.19 g.MUmol(-1) at 80 kVp/120 mAs and 140 kVp/60 mAs respectively), on the other
      hand the influence of mAs value is negligible. 

PMID- 25571148
TI  - Characterization of myocardial iron overload by dual-energy computed tomography
      compared to T2* MRI. A phantom study.
AB  - Iron toxicity plays a key role in tissue damage in patients with iron overload,
      with induced heart failure being the main cause of death. T2*-weighted magnetic
      resonance imaging (MRI) has been established for evaluating myocardial iron
      overload with strong correlation with biopsy. The recently introduced dual-energy
      computed tomography (DECT) has the potential for evaluating iron overload without
      energy-dependent CT attenuation or tissue fat effects. This study investigates
      the performance of DECT for evaluating myocardial iron overload (based on images
      acquired at four different diagnostic imaging energies of 80, 100, 120, and 140
      kVp) and compare the results to MRI T2* measurements based on DECT and MRI
      experiments on phantoms with calibrated iron concentrations. DECT showed high
      accuracy for evaluating iron overload compared to MRI T2* imaging, which might
      help in patient staging based on the degree of iron overload and independent of
      the implemented imaging energy. 

PMID- 25571149
TI  - Radiation dose reduction in CBCT imaging using K-edge filtering and energy
      weighting.
AB  - This paper presents K-edge filtering and energy weighting methods which enhance
      the contrast with less radiation does. Usually, energy weighting methods are used
      with photon-counting detector based CT for each energy bin data obtained to
      enhance the quality of image. However, we used these methods combine with K-edge
      filtering in energy-integrating detector. Using K-edge filtering, different
      energy bin data for energy weighting methods were obtained, and then energy
      weighting factors were calculated to enhance the contrast of image. We report an
      evaluation of the contrast-to-noise ratio (CNR) of reconstructed image with and
      without these two methods. This evaluation was proceeded with two phantoms; one
      is the phantom created personally, and the other is Sendentexct IQ dental CBCT
      (SENDENTEXCT, EU). As for the phantom created personally, the CNR of images
      reconstructed with these methods were increased than CNR of standard images. It
      was seen that 31% to 81% in each energy weighting method for optimizing each
      material (cortical bone, inner bone, soft tissue, iodine (18.5 g/l), iodine (37
      g/l)). In conclusion, we can enhance the contrast of CT images with less
      radiation dose using K-edge filtering and energy weighting method. 

PMID- 25571150
TI  - Non-convex compressed sensing CT reconstruction based on tensor discrete Fourier
      slice theorem.
AB  - X-ray computed tomography (CT) scanners provide clinical value through high
      resolution and fast imaging. However, achievement of higher signal-to-noise
      ratios generally requires emission of more X-rays, resulting in greater dose
      delivered to the body of the patient. This is of concern, as higher dose leads to
      greater risk of cancer, particularly for those exposed at a younger age.
      Therefore, it is desirable to achieve comparable scan quality while limiting X
      ray dose. One means to achieve this compound goal is the use of compressed
      sensing (CS). A novel framework is presented to combine CS theory with X-ray CT.
      According to the tensor discrete Fourier slice theorem, the 1-D DFT of discrete
      Radon transform data is exactly mapped on a Cartesian 2-D DFT grid. The
      nonuniform random density sampling of Fourier coefficients is made feasible by
      uniformly sampling projection angles at random. Application of the non-convex CS
      model further reduces the sufficient number of measurements by enhancing
      sparsity. The numerical results show that, with limited projection data, the non
      convex CS model significantly improves reconstruction performance over the convex
      model. 

PMID- 25571151
TI  - Academic program models for undergraduate biomedical engineering.
AB  - There is a proliferation of medical devices across the globe for the diagnosis
      and therapy of diseases. Biomedical engineering (BME) plays a significant role in
      healthcare and advancing medical technologies thus creating a substantial demand
      for biomedical engineers at undergraduate and graduate levels. There has been a
      surge in undergraduate programs due to increasing demands from the biomedical
      industries to cover many of their segments from bench to bedside. With the
      requirement of multidisciplinary training within allottable duration, it is
      indeed a challenge to design a comprehensive standardized undergraduate BME
      program to suit the needs of educators across the globe. This paper's objective
      is to describe three major models of undergraduate BME programs and their
      curricular requirements, with relevant recommendations to be applicable in
      institutions of higher education located in varied resource settings. Model 1 is
      based on programs to be offered in large research-intensive universities with
      multiple focus areas. The focus areas depend on the institution's research
      expertise and training mission. Model 2 has basic segments similar to those of
      Model 1, but the focus areas are limited due to resource constraints. In this
      model, co-op/internship in hospitals or medical companies is included which
      prepares the graduates for the work place. In Model 3, students are trained to
      earn an Associate Degree in the initial two years and they are trained for two
      more years to be BME's or BME Technologists. This model is well suited for the
      resource-poor countries. All three models must be designed to meet applicable
      accreditation requirements. The challenges in designing undergraduate BME
      programs include manpower, facility and funding resource requirements and time
      constraints. Each academic institution has to carefully analyze its short term
      and long term requirements. In conclusion, three models for BME programs are
      described based on large universities, colleges, and community colleges. Model 1
      is suitable for research-intensive universities. Models 2 and 3 can be
      successfully implemented in higher education institutions with low and limited
      resources with appropriate guidance and support from international organizations.
      The models will continually evolve mainly to meet the industry needs. 

PMID- 25571152
TI  - Biomedical engineering education--status and perspectives.
AB  - Biomedical Engineering programs are present at a large number of universities all
      over the world with an increasing trend. New generations of biomedical engineers
      have to face the challenges of health care systems round the world which need a
      large number of professionals not only to support the present technology in the
      health care system but to develop new devices and services. Health care
      stakeholders would like to have innovative solutions directed towards solving
      problems of the world growing incidence of chronic disease and ageing population.
      These new solutions have to meet the requirements for continuous monitoring,
      support or care outside clinical settlements. Presence of these needs can be
      tracked through data from the Labor Organization in the U.S. showing that
      biomedical engineering jobs have the largest growth at the engineering labor
      market with expected 72% growth rate in the period from 2008-2018. In European
      Union the number of patents (i.e. innovation) is the highest in the category of
      biomedical technology. Biomedical engineering curricula have to adopt to the new
      needs and for expectations of the future. In this paper we want to give an
      overview of engineering professions in related to engineering in medicine and
      biology and the current status of BME education in some regions, as a base for
      further discussions. 

PMID- 25571153
TI  - Education of biomedical engineering in Taiwan.
AB  - Biomedical Engineers (BME) play an important role in medical and healthcare
      society. Well educational programs are important to support the healthcare
      systems including hospitals, long term care organizations, manufacture industries
      of medical devices/instrumentations/systems, and sales/services companies of
      medical devices/instrumentations/system. In past 30 more years, biomedical
      engineering society has accumulated thousands people hold a biomedical
      engineering degree, and work as a biomedical engineer in Taiwan. Most of BME
      students can be trained in biomedical engineering departments with at least one
      of specialties in bioelectronics, bio-information, biomaterials or biomechanics.
      Students are required to have internship trainings in related institutions out of
      campus for 320 hours before graduating. Almost all the biomedical engineering
      departments are certified by IEET (Institute of Engineering Education Taiwan),
      and met the IEET requirement in which required mathematics and fundamental
      engineering courses. For BMEs after graduation, Taiwanese Society of Biomedical
      Engineering (TSBME) provides many continue-learning programs and certificates for
      all members who expect to hold the certification as a professional credit in his
      working place. In current status, many engineering departments in university are
      continuously asked to provide joint programs with BME department to train much
      better quality students. BME is one of growing fields in Taiwan. 

PMID- 25571154
TI  - First experience with a new biomedical engineering program in Slovenia
      established following the TEMPUS IV CRH-BME joint project guidelines.
AB  - A new study program of biomedical engineering was recently established at Faculty
      of Electrical Engineering, University of Ljubljana, Slovenia. It is based on the
      long-lasting tradition of education in the field of BME at the host institution
      and is built on the BME areas in which the research groups of the Faculty of
      Electrical Engineering have been traditionally successful. The program was
      prepared in accordance with the recommendations of the TEMPUS IV CRH-BME Project
      consortium. 

PMID- 25571155
TI  - Using biomedical engineering and "hidden capital" to provide educational outreach
      to disadvantaged populations.
AB  - A hands-on learning module called "Science of the Slam" is created that taps into
      the passions and interests of an under-represented group in the fields of
      Science, Technology, Engineering and Mathematics (STEM). This is achieved by
      examining the use of the scientific method to quantify the biomechanics of
      basketball players who are good at performing the slam dunk. Students already
      have an intrinsic understanding of the biomechanics of basketball however this
      "hidden capital" has never translated into the underlying STEM concepts. The
      effectiveness of the program is rooted in the exploitation of "hidden capital"
      within the field of athletics to inform and enhance athletic performance. This
      translation of STEM concepts to athletic performance provides a context and a
      motivation for students to study the STEM fields who are traditionally disengaged
      from the classic engineering outreach programs. "Science of the Slam" has the
      potential to serve as a framework for other researchers to engage under
      represented groups in novel ways by tapping into shared interests between the
      researcher and disadvantaged populations. 

PMID- 25571156
TI  - Extended student quality improvement programs of Xiamen University.
AB  - This paper describes the recent educational activities and programs organized by
      the IEEE Engineering in Medicine and Biology Society (EMBS) Xiamen University
      Student Club. The educational programs covered the undergraduate student
      mentoring program, seminar series, the top-quality course project, and student
      scientific projects and contests. These activities have successfully cultivated
      our students strong interests in the field of biomedical engineering, and also
      trained our students the skills of solving real-world problems and experience of
      teamwork collaborations. Our initiatives provide a good example of well-organized
      education practice for IEEE EMBS student organizations. 

PMID- 25571157
TI  - Virtual firm in biomedical education: a very successful experience.
AB  - In May 2006, the Institut Superieur d'Ingenieurs de Franche-Comte (ISIFC)
      launched its own virtual firm, which was named Biotika(r) by students. Virtual
      means that this company has no real legal status. It is a pedagogic model;
      however, the situation scenario for the ISIFC student engineers is real. They are
      currently working in real conditions on the development of new medical devices
      and on the modernization of medical products. The need for these innovative
      medical devices was identified by the students during their second-year (6 weeks)
      internship in hospitals. Biotika(r) is open between March and December every
      year. The students are "recruited" following an imitation job interview and each
      is then entrusted with a mission (engineer, project manager etc.) in one of the
      company's four departments: Research & Design, Quality-regulatory affairs,
      Clinical investigations, and Public relations-marketing. The personnel of
      Biotika(r) work on the development of innovative medical devices and/or the
      preparation of CE or FDA certification for 2 days per week. Since its launch,
      Biotika(r) has developed eight products and obtained many grants and prizes from
      French research and governmental organizations. It is also certified ISO 13485.

PMID- 25571158
TI  - Wearable ballistocardiography: preliminary methods for mapping surface vibration
      measurements to whole body forces.
AB  - The recent resurgence of ballistocardiogram (BCG) measurement and interpretation
      technologies has led to a wide range of powerful tools available for
      unobtrusively assessing mechanical aspects of cardiovascular health at home.
      Researchers have demonstrated a multitude of modern BCG measurement modalities,
      including beds, chairs, weighing scales, and wearable approaches. However, many
      modalities produce significant variations in the morphology of the measured BCG,
      creating confusion in the analysis and interpretation of the signals. This paper
      creates a framework for comparing wearable BCG measurements to whole body
      measurements--such as taken with a weighing scale system--to eventually allow the
      same analysis and interpretation tools that have been developed for whole body
      systems to be applied in the future to wearable systems. To the best of our
      knowledge, it represents the first attempt to morphologically compare vertical
      acceleration recordings measured on different locations on the torso to whole
      body displacements measured by BCG instrumentation.

PMID- 25571159
TI  - Evaluation of ensemble averaging methods in 3D ballistocardiography.
AB  - Ballistocardiography (BCG) is a non-invasive technique which measures the
      acceleration of a body induced by cardiovascular activity, namely the force
      exerted by the beating heart. Measuring a BCG in a gravity-free environment
      provides ideal conditions where the subject is completely decoupled from its
      environment. Furthermore, because gravity constrains the motion in two
      dimensions, the non-negligible accelerations taking place in the third dimension
      are lost. In every experimental situation, the measured BCG signal contains
      artifacts pertaining to different causes. One of them is the undesirable
      involuntary movements of the subject. Ensemble averaging (EA) tackles the issue
      of constructing a typical one cardiac cycle BCG signal which best represents a
      longer recording. The present work compares state-of-the-art EA methods and
      proposes two novel techniques, one taking into account the ECG sub-intervals and
      the other one based on Dynamic Time Warping. The effects of lung volume are also
      assessed. 

PMID- 25571160
TI  - Standing ballistocardiography measurements in microgravity.
AB  - The performance and practicality of a scale-based ballistocardiogram (BCG) system
      for hemodynamic monitoring of astronauts on extended space missions was
      demonstrated. The system consists of a modified electronic weighing scale fitted
      with foot bindings to mechanically couple the subject to the scale. This system
      was tested on a recent series of parabolic flights in which scale-based and
      accelerometry-based free-floating BCG of 10 subjects was measured in
      microgravity. The signal-to-noise ratio (SNR) of the scale-based BCG was, on
      average, a factor of 2.1 (6.3 dB) higher than the free-floating method,
      suggesting that the tethered scale approach might be more robust in terms of
      signal quality. Additionally, this approach enables practical BCG-based
      hemodynamic monitoring in fractional-g environments, and on small space vehicles
      such as NASA's upcoming Orion capsule. The scale-based results in microgravity
      were also compared to ground measurements (1 g), where there was an average 38.7
      ms RJ interval reduction from ground to microgravity environments that is
      consistent across 9 of 10 subjects. This phenomenon is likely due to the
      transient increase in venous return, and consequent decrease in pre-ejection
      period, experienced during the microgravity time intervals.

PMID- 25571161
TI  - Ballistocardiography for nonintrusive sleep structure estimation.
AB  - Based on the its nonintrusive characteristics, ballistocardiography(BCG) has
      applied in the estimation of sleep structure without attaching any sensors to the
      subject's body. Loadcell or polyvinylidenefluoride (PVDF) film sensors are
      installed on the mattress for the monitoring of BCG. BCG peak was detected and
      heart rate variability parameters are derived. Parameters representing sleep
      structure and quality are estimated using these parameters. Sleep efficiency,
      four stages of sleep structure and sleep onset latency are estimated and results
      are compared with the results derived from polysomnographic recording.

PMID- 25571162
TI  - Tracking clinical status for heart failure patients using ballistocardiography
      and electrocardiography signal features.
AB  - Heart failure (HF) is an escalating public health problem, with few effective
      methods for home monitoring. In HF management, the important clinical factors to
      monitor include symptoms, fluid status, cardiac output, and blood pressure--based
      on these factors, inotrope and diuretic dosages are adjusted day-by-day to
      control the disorder and improve the patient's status towards a successful
      discharge. Previously, the ballistocardiogram (BCG) measured on a weighing scale
      has been shown to be capable of detecting changes in cardiac output and
      contractility for healthy subjects. In this study, we investigated whether the
      BCG and electrocardiogram (ECG) signals measured on a wireless modified scale
      could accurately track the clinical status of HF patients during their hospital
      stay. Using logistic regression, we found that the root-mean-square (RMS) power
      of the BCG provided a good fit for clinical status, as determined based on
      clinical measurements and symptoms, for the 85 patient days studied from 10
      patients (p < 0.01). These results provide a promising foundation for future
      studies aimed at using the BCG/ECG scale at home to track HF patient status
      remotely.

PMID- 25571164
TI  - Phase and magnitude spatiotemporal dynamics of beta oscillation in
      electrocorticography (ECoG) in the monkey motor cortex at the onset of 3D
      reaching movements.
AB  - beta oscillations in local field potentials, electro-corticography (ECoG), and
      electroencephalograms (EEG) are ubiquitous in the motor cortex of monkeys and
      humans. However due to their lack of contributions, compared to other frequency
      ranges, to decode effector kinematics especially in ECoG signals, spatiotemporal
      dynamics of ECoG beta oscillations has not been examined despite the larger areas
      that ECoG arrays can cover than standard intracortical multielectrode arrays.
      Here, we used ECoG grids to cover large areas of motor cortex and some
      somatosensory cortex in monkeys while they performed an unconstrained reaching
      and a lever pulling task at two force levels in three dimensional space. We
      showed that under the pulling task beta power increased around movement onset.
      However, the beta phases were locked around the movement onsets and their peak
      timings were spatially aligned in the motor cortex. These results may indicate
      that spatiotemporal dynamics of beta oscillation conveys task relevant
      information and that ECoG arrays will be useful to study larger spatiotemporal
      patterns in the motor cortex, or any cortical areas in general, than
      intracortical multielectrode arrays. 

PMID- 25571165
TI  - Instantaneous interactions between brain sites can distinguish movement from rest
      but are relatively poor at resolving different movement types.
AB  - Classification of finger movements from brain signals is an important problem in
      emerging neural prosthetics research. Current techniques have focused primarily
      on aggregating data from different brain sites independently, without regard to
      the interaction between different brain sites. We performed a very simple
      experiment classifying finger movements during electrocorticographic recording
      from motor cortex. Unlike previous experiments of this type, we examined whether
      the most-simple type of instantaneous interactions between brain regions could
      improve classification. We focused on two simple, but salient markers: phase
      coherence of the 12-20 Hz beta range, and simple correlation in broadband
      spectral change. We compared behavioral classification using these interactions
      with simple amplitude changes in beta and broadband magnitude. We found that
      inter-electrode phase coherence and cross-correlation, were relatively poor at
      distinguishing between finger movements, and only mediocre at identifying
      null/rest periods. 

PMID- 25571163
TI  - Multi-modal decoding: longitudinal coherency changes between spike trains, local
      field potentials and electrocorticogram signals.
AB  - Neural information degeneracy in chronic implants due to signal instabilities
      affects optimal performance of brain-machine interfaces (BMIs). Spike-decoders
      are more vulnerable compared to those using LFPs and ECoG signals. In order for
      BMIs to perform reliably across years, decoders should be able to use neural
      information contained in various signal modalities. Hence, it is important to
      identify information redundancy among signal types. In this work, spikes, LFPs
      and ECoGs were recorded simultaneously from motor cortex of a rhesus monkey,
      while the animal was learning to control a multi-DOF robot with a spike-decoder.
      As the behavioral performance increased, the linear association among the signal
      types increased. Coherency of these signals increased in specific frequency bands
      as learning occurred. These results suggest the possibility of substituting the
      information lost in one modality by another. 

PMID- 25571166
TI  - Patient-specific contour-fitting sheet electrodes for electrocorticographic brain
      machine interfaces.
AB  - Non-invasive localization of certain brain functions may be mapped on a
      millimeter level. However, the inter-electrode spacing of common clinical brain
      surface electrodes still remains around 10 mm, and some electrodes fail to
      measure cortical activity due to unconformable plain electrode sheets. Here, we
      present details on development of implantable electrodes for attaining higher
      quality electrocorticographic signals for use in functional brain mapping and
      brain-machine interfaces. We produced personalized sheet electrodes after the
      creation of individualized molds using a 3D-printer. We created arrays to fit the
      surface curvature of the brain and inside the central sulcus, with inter
      electrode distances of 2.5 mm. Rat experiments undertaken indicated no long term
      toxicity. We were also able to custom design, rapidly manufacture, safely implant
      and confirm the efficacy of personalized electrodes, including the capability to
      attain meaningful high gamma-band information in an amyotrophic lateral sclerosis
      patient. This sheet electrode may contribute to the higher performance of BMI's. 

PMID- 25571167
TI  - Super multi-channel recording systems with UWB wireless transmitter for BMI.
AB  - In order to realize a low-invasive and high accuracy Brain-Machine Interface
      (BMI) system for clinical applications, a super multi-channel recording system
      was developed in which 4096 channels of Electrocorticogram (ECoG) signal can be
      amplified and transmitted to outside the body by using an Ultra Wide Band (UWB)
      wireless system. Also, a high density, flexible electrode array made by using a
      Parylene-C substrate was developed that is composed of units of 32-ch recording
      arrays. We have succeeded in an evaluation test of UWB wireless transmitting
      using a body phantom system. 

PMID- 25571168
TI  - Neuroprosthetic limb control with electrocorticography: approaches and
      challenges.
AB  - Advanced upper limb prosthetics, such as the Johns Hopkins Applied Physics Lab
      Modular Prosthetic Limb (MPL), are now available for research and preliminary
      clinical applications. Research attention has shifted to developing means of
      controlling these prostheses. Penetrating microelectrode arrays are often used in
      animal and human models to decode action potentials for cortical control. These
      arrays may suffer signal loss over the long-term and therefore should not be the
      only implant type investigated for chronic BMI use. Electrocorticographic (ECoG)
      signals from electrodes on the cortical surface may provide more stable long-term
      recordings. Several studies have demonstrated ECoG's potential for decoding
      cortical activity. As a result, clinical studies are investigating ECoG encoding
      of limb movement, as well as its use for interfacing with and controlling
      advanced prosthetic arms. This overview presents the technical state of the art
      in the use of ECoG in controlling prostheses. Technical limitations of the
      current approach and future directions are also presented. 

PMID- 25571169
TI  - Models for predicting stage in head and neck squamous cell carcinoma using
      proteomic data.
AB  - Head and neck squamous cell carcinoma (HNSCC) that is detected at an advanced
      stage is associated with much worse patient outcomes than if detected at early
      stages. This study uses reverse phase protein array (RPPA) data to build
      predictive models that discriminate between early and advanced stage HNSCC.
      Individual and ensemble binary classifiers, using filter-based and wrapper-based
      feature selection, are used to build several models which achieve moderate MCC
      and AUC values. This study identifies informative protein feature sets which may
      contribute to an increased understanding of the molecular basis of HNSCC. 

PMID- 25571170
TI  - Modeling order-disorder transition in Low-Density Lipoprotein.
AB  - Low Density Lipoproteins (LDL) undergo a reversible order-disorder thermal
      transition close to biological temperature due to cooperative melting of the
      cholesteryl esters (CE) in the core of the LDL particle. We have noticed that
      chain-chain interactions between CE molecules are responsible for the stability
      of the ordered smectic phase; thus, we formulated a simple "coarse-grained" two
      state model to describe the melting process. In this model only nearest neighbor
      interactions are allowed. On the basis of these assumptions we performed
      Metropolis Monte Carlo (MC) simulation in order to obtain the heat capacity
      curve. The resulting profile reveals well-known features of the systems with a
      finite size. 

PMID- 25571171
TI  - The effects of cell asynchrony on time-series data: an analysis on gene
      expression level of Plasmodium falciparum.
AB  - To investigate the intraerythrocytic cycle of Plasmodium falciparum, time-series
      gene expression data are measured of infected red blood cells. However, the
      observed data is blurred due to cell asynchrony during experiments. In this
      paper, the effects of cell asynchrony are investigated by conducting numerical
      experiments. The simulation results suggest that cell asynchrony has varying
      effects on different intrinsic expression patterns. Specifically, the intrinsic
      patterns with high expression around the late life stage are more likely to be
      affected by cell asynchrony. It is also investigated how the effects of cell
      asynchrony are influenced by the experimental conditions. Certain parameters are
      identified that have a strong effects on cell asynchrony, and these parameters
      should be measured during biological experiments in order to deblur time-series
      gene expression data. 

PMID- 25571172
TI  - Exact computation of probability landscape of stochastic networks of Single Input
      and Coupled Toggle Switch Modules.
AB  - Gene regulatory networks depict the interactions between genes, proteins, and
      other components of the cell. These interactions often are stochastic that can
      influence behavior of the cells. Discrete Chemical Master Equation (dCME)
      provides a general framework for understanding the stochastic nature of these
      networks. However solving dCME is challenging due to the enormous state space,
      one effective approach is to study the behavior of individual modules of the
      stochastic network. Here we used the finite buffer dCME method and directly
      calculated the exact steady state probability landscape for the two stochastic
      networks of Single Input and Coupled Toggle Switch Modules. The first example is
      a switch network consisting of three genes, and the second example is a double
      switching network consisting of four coupled genes. Our results show complex
      switching behavior of these networks can be quantified. 

PMID- 25571173
TI  - Investigation of factors affecting RNA-seq gene expression calls.
AB  - RNA-seq enables quantification of the human transcriptome. Estimation of gene
      expression is a fundamental issue in the analysis of RNA-seq data. However, there
      is an inherent ambiguity in distinguishing between genes with very low expression
      and experimental or transcriptional noise. We conducted an exploratory
      investigation of some factors that may affect gene expression calls. We observed
      that the distribution of reads that map to exonic, intronic, and intergenic
      regions are distinct. These distributions may provide useful insights into the
      behavior of gene expression noise. Moreover, we observed that these distributions
      are qualitatively similar between two sequence mapping algorithms. Finally, we
      examined the relationship between gene length and gene expression calls, and
      observed that they are correlated. This preliminary investigation is important
      for RNA-seq gene expression analysis because it may lead to more effective
      algorithms for distinguishing between true gene expression and experimental or
      transcriptional noise. 

PMID- 25571174
TI  - State machine modeling of MAPK signaling pathways.
AB  - Mitogen activated protein kinase (MAPK) signaling pathways are frequently
      deregulated in human cancers with potential involvement in most if not all
      cellular processes leading to tumorigenesis. Mathematical/computational models of
      MAPK signaling are indispensable to the study of pathway deregulation dynamics
      and their nonlinear effects on cell fate and carcinogenesis. A finite state
      machine model of MAPK cellular signaling is explored as an alternative to
      differential equations-based models of kinetics. The proposed approach is applied
      to the Ras-Extracellular signal-regulated kinase (Ras-ERK) pathway which includes
      the frequently mutated Ras and RAF proteins in many types of carcinomas. 

PMID- 25571175
TI  - Chronic, percutaneous connector for electrical recording and stimulation with
      microelectrode arrays.
AB  - The translation of advances in neural stimulation and recording research into
      clinical practice hinges on the ability to perform chronic experiments in awake
      and behaving animal models. Advances in microelectrode array technology, most
      notably flexible polymer arrays, have significantly improved reliability of the
      neural interface. However, electrical connector technology has lagged and is
      prone to failure from non-biocompatibility, large size, contamination, corrosion,
      and difficulty of use. We present a novel chronic, percutaneous electrical
      connector system that is suitable for neural stimulation and recording. This
      system features biocompatible materials, low connect and disconnect forces,
      passive alignment, and a protective cap during non-use. We have successfully
      designed, assembled, and tested in vitro both a 16-channel system and a high
      density 64-channel system. Custom, polyimide, 16-channel, microelectrode arrays
      were electrically assembled with the connector system and tested using cyclic
      voltammetry and electrochemical impedance spectroscopy. This connector system is
      versatile and can be used with a variety of microelectrode array technologies for
      chronic studies. 

PMID- 25571176
TI  - Fabrication and characterization of a high-resolution neural probe for
      stereoelectroencephalography and single neuron recording.
AB  - This paper reports on the design, fabrication, and characterization of neural
      probes for stereoelectroencephalography (SEEG). The probe specifically targets
      focal epilepsy as key application. However, probes of this type can also be used
      for the diagnosis and treatment of other neural dysfunctions such as Parkinson's
      disease or tremor, typically requiring deep brain probes. The probe fabrication,
      of which most processes are parallel batch processes, relies on a novel
      fabrication concept for rolling and gluing thin film polyimide sheets with
      integrated electrodes into permanent cylindrical shapes with diameters down to
      800 MUm. The SEEG probes, comprise several macro-electrodes designed to record
      local field potentials, and micro-electrodes positioned in-between, dedicated to
      monitoring single unit activity, with a total channel count of 32, despite the
      small diameter. While platinum micro-electrodes with a diameter of 35 MUm have
      impedances of about 255 kOmega at 1 kHz, impedance values down to about 1.5
      kOmega have been measured for the macro-electrodes. The devices have shown good
      compatibility with magnetic resonance imaging in a 9.4 T magnet, enabling the
      precise post-operative probe localization within the brain. 

PMID- 25571177
TI  - Equivalency between emulated disc electrodes and conventional disc electrode
      human electroencephalography.
AB  - We have previously shown that tripolar concentric ring electrode (TCRE) Laplacian
      electroencephalography (tEEG) has significantly better signal-to-noise ratio,
      spatial resolution, and mutual information than disc electrode
      electroencephalography (EEG). This paper compares the EEG signals acquired
      simultaneously from the outer ring of the TCRE (oTCRE), shorting all three
      elements of the TCRE (sTCRE) and disc electrode (disc) concurrently from nearly
      the same location on the human scalp. We calculated the average correlation for
      the time series between each pair of signals and average coherence over the pass
      band frequencies between all pairs of signals as well. All the correlations and
      coherences were above 0.99. The results suggest that the oTCRE can be used to
      record EEG concurrently with tEEG from the same sensor at the same location. 

PMID- 25571178
TI  - Miniaturized tool for optogenetics based on an LED and an optical fiber
      interfaced by a silicon housing.
AB  - This paper reports on the design, simulation, fabrication and characterization of
      a tool for optogenetic experiments based on a light emitting diode (LED). A
      minimized silicon (Si) interface houses the LED and aligns it to an optical
      fiber. With a Si housing size of 550*500*380 MUm(3) and an electrical
      interconnection of the LED by a highly flexible polyimide (PI) ribbon cable is
      the system very variable. PI cables and Si housings are fabricated using
      established microsystem technologies. A 270*220*50 MUm(3) bare LED chip is flip
      chip-bonded onto the PI cable. The Si housing is adhesively attached to the PI
      cable, thereby hosting the LED in a recess. An opposite recess guides the optical
      fiber with a diameter of 125 MUm. An aperture in-between restricts the emitted
      LED light to the fiber core. The optical fiber is adhesively fixed into the Si
      housing recess. An optical output intensity at the fiber end facet of 1.71
      mW/mm(2) was achieved at a duty cycle of 10 % and a driving current of 30 mA. 

PMID- 25571179
TI  - A low-cost, multiplexed electrophysiology system for chronic MUECoG recordings in
      rodents.
AB  - Micro-Electrocorticography (MUECoG) offers a minimally invasive, high resolution
      interface with large areas of cortex. However, large arrays of electrodes with
      many contacts that are individually wired to external recording systems are
      cumbersome and make chronic recording in freely behaving small animals
      challenging. Multiplexed headstages overcome this limitation by combining the
      signals from many electrodes to a smaller number of connections directly on the
      animal's head. Commercially available multiplexed headstages provide high
      performance integrated amplification, multiplexing and analog to digital
      conversion. However, the cost of these systems can be prohibitive for small labs
      or for experiments that require a large number of animals to be continuously
      recorded at the same time. Here we have developed a multiplexed 60-channel
      headstage amplifier optimized to chronically record electrophysiological signals
      from high-density MUECoG electrode arrays. A single, ultraflexible (2 mm
      thickness) microHDMI cable provided the data interface. Using low cost
      components, we have reduced the cost of the multiplexed headstage to ~$125.
      Paired with a custom interface printed circuit board (PCB) and a general purpose
      data acquisition system (M-series DAQ, National Instruments), an inexpensive and
      customizable electrophysiology system is assembled. Open source LabVIEW software
      that we have previously released controlled the system. It can also be used with
      other open source neural data acquisition packages. Combined, we have presented a
      scalable, low-cost platform for high-channel count electrophysiology.

PMID- 25571180
TI  - An 8-channel neural spike processing IC with unsupervised closed-loop control
      based on spiking probability estimation.
AB  - This paper presents a neural spike processing IC for simultaneous spike
      detection, alignment, and transmission on 8 recording channels with unsupervised
      closed-loop control. In this work, spikes are detected according to online
      estimated spiking probability maps, which reliably predict the possibility of
      spike occurrence. The closed-loop control has been made possible by estimating
      firing rates based on alignment results and turning on/off channels individually
      and automatically. The 8-channel neural spike processing IC, implemented in a
      0.13 MUm CMOS process, has a varied power dissipation from 36 MUW to 54.4 MUW per
      channel at a voltage supply of 1.2 V. The chip also achieves a 380* data rate
      reduction for the testing in vivo data, allowing easy integration with wireless
      data transmission modules. 

PMID- 25571181
TI  - Challenges in wearable personal health monitoring systems.
AB  - Wearable sensors give the users convenience in daily health monitoring, though
      several challenges in such sensor systems should be overcome. This paper
      discusses the challenges in wearable health monitoring sensors and solutions for
      multi-modal and multi-functional wrist-worn devices based on novel circuit design
      techniques to reject DC offset. This paper also presents a novel sophisticated
      algorithm to reject motion artifacts. The system has the capability to
      simultaneously acquire several biomedical signals (i.e. electrocardiogram, PPG,
      and body-electrode impedance). The system can also help patients who want to
      monitor their psychological signals to mitigate health risks. 

PMID- 25571182
TI  - Three-dimensional, flexible graphene bioelectronics.
AB  - We report 3-dimensional (3D) graphene-based biosensors fabricated via 3D transfer
      of monolithic graphene-graphite structures. This mechanically flexible all-carbon
      structure is a prospective candidate for intimate 3D interfacing with biological
      systems. Monolithic graphene-graphite structures were synthesized using low
      pressure chemical vapor deposition (LPCVD) process relying on the
      heterostructured metal catalyst layers. Nonplanar substrates and wet-transfer
      method were used with a thin Au film as a transfer layer to achieve the 3D
      graphene structure. Instead of the typical wet-etching method, vapor-phase
      etching was performed to minimize the delamination of the graphene while removing
      the transfer layer. We believe that the monolithic graphene-graphite synthesis
      combined with the conformal 3D transfer will pave the way for the 3D conformal
      sensing capability as well as the intracellular recording of living cells in the
      future. 

PMID- 25571183
TI  - Bioelectric interfaces for the peripheral nervous system.
AB  - The peripheral nervous system (PNS) is an attractive target for those developing
      neural interfaces as an access point to the information flow coursing within our
      bodies. A successful neural interface could not only offer the means to
      understand basic neurophysiological mechanisms, such as how the body accomplishes
      complex coordinated control of multi degree of freedom body segments, but also
      could serve as the means of delivering treatment or therapies to restore
      physiological functions lost due to injury or disease. Our work in the
      development of such a neural interface focuses upon multi-microelectrode devices
      that are placed within the body of the nerve fascicle; mulit-channel intra
      fascicular devices called the thin-film Longitudinal Intra-Fascicular Electrode
      (tfLIFE) and the Transversely Implanted Multi-Electrode (TIME). These structures
      provide high resolution access to the PNS and have demonstrated promise in animal
      work as well as in preliminary sub-acute work in human volunteers. However, work
      remains to improve upon their longevity and biocompatibility before full
      translation to clinical work can occur.

PMID- 25571184
TI  - Metallic glass nanofibers in future hydrogel-based scaffolds.
AB  - Electrically conductive reinforced hydrogels offer a wide range of applications
      as three-dimensional scaffolds in tissue engineering. We report electrical and
      mechanical characterization of methacrylated gelatin (GelMA) hydrogel, containing
      palladium-based metallic glass nanofibers (MGNF). Also we show that the fibers
      are biocompatible and C2C12 myoblasts in particular, planted into the hybrid
      hydrogel, tend to attach to and elongate along the fibers. The MGNFs in this work
      were created by gas atomization. Ravel of fibers were embedded in the GelMA
      prepolymer in two different concentrations (0.5 and 1.0 mg/ml), and then the
      ensemble was cured under UV light, forming the hybrid hydrogel. The conductivity
      of the hybrid hydrogel was proportional to the fiber concentration. 

PMID- 25571185
TI  - Modeling and simulation of crossing magnetic nanoparticles through blood brain
      barrier (BBB).
AB  - Crossing the Blood Brain Barrier (BBB), despite its tight junctions, is of the
      great importance in a plethora of medical applications. As a result, this work is
      dedicated to molecular dynamics (MD) simulation of crossing through the BBB
      particularly under the effect of magnetic force. For this purpose, two cases of a
      coated gold nanocparticle with insulin and uncoated gold nanoparticle have been
      considered; there, the dominant governing parameters in each case are changed to
      identify the optimized condition for crossing nanoparticles. These parameters are
      of biological (ligand-receptor binding affinity), biophysical (membrane surface
      receptor density ratio and non-specific interaction parameter) or geometrical
      (size of components) origin. The most important part of this study is MD
      simulation of nanoparticles under the effect of magnetic field and the result
      shows that for crossing through BBB what force profile must be provided by the
      magnetic field. 

PMID- 25571186
TI  - A low-power current-reuse dual-band analog front-end for multi-channel neural
      signal recording.
AB  - Thoroughly studying the brain activity of freely moving subjects requires
      miniature data acquisition systems to measure and wirelessly transmit neural
      signals in real time. In this application, it is mandatory to simultaneously
      record the bioelectrical activity of a large number of neurons to gain a better
      knowledge of brain functions. However, due to limitations in transferring the
      entire raw data to a remote base station, employing dedicated data reduction
      techniques to extract the relevant part of neural signals is critical to decrease
      the amount of data to transfer. In this work, we present a new dual-band neural
      amplifier to separate the neuronal spike signals (SPK) and the local field
      potential (LFP) simultaneously in the analog domain, immediately after the pre
      amplification stage. By separating these two bands right after the pre
      amplification stage, it is possible to process LFP and SPK separately. As a
      result, the required dynamic range of the entire channel, which is determined by
      the signal-to-noise ratio of the SPK signal of larger bandwidth, can be relaxed.
      In this design, a new current-reuse low-power low-noise amplifier and a new dual
      band filter that separates SPK and LFP while saving capacitors and pseudo
      resistors. A four-channel dual-band (SPK, LFP) analog front-end capable of
      simultaneously separating SPK and LFP is implemented in a TSMC 0.18 MUm
      technology. Simulation results present a total power consumption per channel of
      3.1 MUw for an input referred noise of 3.28 MUV and a NEF for 2.07. The cutoff
      frequency of the LFP band is fc=280 Hz, and fL=725 Hz and fL=11.2 KHz for SPK,
      with 36 dB gain for LFP band 46 dB gain for SPK band. 

PMID- 25571187
TI  - Home-based tele-assisted robotic rehabilitation of joint impairments in children
      with cerebral palsy.
AB  - A portable rehabilitation robot incorporating intelligent stretching, robot
      guided voluntary movement training with motivating games and tele-rehabilitation
      was developed to provide convenient and cost-effective rehabilitation to children
      with cerebral palsy (CP) and extend rehabilitation care beyond hospital.
      Clinicians interact with the patients remotely for periodic evaluations and
      updated guidance. The tele-assisted stretching and active movement training was
      done over 6-week 18 sessions on the impaired ankle of 23 children with CP in
      their home setting. Treatment effectiveness was evaluated using biomechanical
      measures and clinical outcome measures. After the tele-assisted home robotic
      rehabilitation intervention, there were significant increases in the ankle
      passive and active range of motion, muscle strength, a decrease in spasticity,
      and increases in balance and selective control assessment of lower-extremity. 

PMID- 25571188
TI  - Feasibility of a bimanual, lever-driven wheelchair for people with severe arm
      impairment after stroke.
AB  - Individuals with severe arm impairment after stroke are thought to be unable to
      use a manual wheelchair in the conventional bimanual fashion, because they cannot
      grip and push the pushrim with their impaired hand. Instead, they are often
      taught to propel a wheelchair with their good arm and leg, a compensatory
      strategy that encourages disuse and may cause asymmetric tone. Here, we show that
      four stroke survivors (9, 27 50 and 16 months post stroke) with severe arm
      impairment (upper extremity Fugl Meyer scores of 21, 17, 16 and 15 of 66
      respectively) were able to propel themselves overground during ten, 3.3 meter
      movement trials, using a specially designed lever-driven wheelchair adapted with
      a splint and elastic bands. Their average speed on the tenth trial was about 0.1
      m/sec. These results suggest that individuals with stroke could use bimanual
      wheelchair propulsion for mobility, both avoiding the problems associated with
      good-arm/good-leg propulsion and increasing the number of daily arm movements
      they achieve, which may improve arm movement recovery. 

PMID- 25571190
TI  - Mobile robotic assistive balance trainer - an intelligent compliant and adaptive
      robotic balance assistant for daily living.
AB  - Balance control probably has the greatest impact on independence in activities of
      daily living (ADL), because it is a fundamental motor skill and prerequisite to
      the maintenance of a myriad of postures and mobile activities. We propose a new
      rehabilitation therapy to administer standing and mobile balance control
      training, enabled by a Mobile Robotic Assistive Balance Trainer (MRABT). The
      targeted group for this initial work is post stroke patients, although it can be
      extended to subjects with other neurological insults in the future. The proposed
      system consists of a mobile base and a parallel robotic arm which provides
      support to the patient at the hip. The compliant robotic arm with intelligent
      control algorithm will only provide support and assistance to the patient when
      the center of mass of the body deviates beyond the predefined safety boundary,
      mimicking the helping hands of a parent when a toddler learns to walk. In this
      paper, we present our initial work in the design and kinematic analysis of the
      system. 

PMID- 25571189
TI  - Reduction of stroke assessment time for visually guided reaching task on KINARM
      exoskeleton robot.
AB  - Robotic technologies provide objective, highly reliable tools for assessment of
      brain function following stroke. KINARM is an exoskeleton device that quantifies
      sensorimotor brain function using a visually guided reaching task among many
      other behavioral tasks. As further tasks are developed to more broadly assess
      different aspects of behavior using the robot, techniques and approaches are
      required to reduce the time it takes to complete each task. The present study
      investigates how the value of robot-measured parameters changes under alternative
      schemes that significantly reduce assessment time compared to the current
      assessment protocol for the visually guided reaching task. Results of the study
      are validated by addressing an important diagnostic question using an SVM
      classifier, showing that the alternative schemes provide nearly identical
      performance in terms of classification sensitivity, specificity and accuracy. 

PMID- 25571191
TI  - Optimizing learning of a locomotor task: amplifying errors as needed.
AB  - Research on motor learning has emphasized that errors drive motor adaptation.
      Thereby, several researchers have proposed robotic training strategies that
      amplify movement errors rather than decrease them. In this study, the effect of
      different robotic training strategies that amplify errors on learning a complex
      locomotor task was investigated. The experiment was conducted with a one degree
      of freedom robotic stepper (MARCOS). Subjects were requested to actively
      coordinate their legs in a desired gait-like pattern in order to track a
      Lissajous figure presented on a visual display. Learning with three different
      training strategies was evaluated: (i) No perturbation: the robot follows the
      subjects' movement without applying any perturbation, (ii) Error amplification:
      existing errors were amplified with repulsive forces proportional to errors,
      (iii) Noise disturbance: errors were evoked with a randomly-varying force
      disturbance. Results showed that training without perturbations was especially
      suitable for a subset of initially less-skilled subjects, while error
      amplification seemed to benefit more skilled subjects. Training with error
      amplification, however, limited transfer of learning. Random disturbing forces
      benefited learning and promoted transfer in all subjects, probably because it
      increased attention. These results suggest that learning a locomotor task can be
      optimized when errors are randomly evoked or amplified based on subjects' initial
      skill level. 

PMID- 25571192
TI  - Measurement of rehabilitation in thumb MP joint subluxation due to rheumatoid
      arthritis.
AB  - As treatment for subluxation due to rheumatoid arthritis (RA), rehabilitation by
      hand therapy is one option, but the number of therapist is not sufficient.
      Therefore, a device for rehabilitation of thumb metacarpophalangeal (MP) joint
      subluxation has been developed. To improve the device, it is necessary to measure
      in close proximity to the actual rehabilitation. Therefore, the authors tried to
      measure two kinds of rehabilitation by using motion capture and a contact force
      sensor. To measure rehabilitation movements, three markers were attached to the
      metacarpal bone, six markers were attached to each side of the interphalangeal
      (IP) joint, MP joint and proximal phalanx of the right thumb of the subjects, and
      a finger model was created by these markers. Further, three markers were placed
      on the left index of the therapist, and force direction was calculated by these
      markers. Measurement was conducted on healthy subjects, Rehabilitation was
      performed by the person who is not a therapist, but received the guidance of the
      doctor who is coauthor. As a result, the authors could measure rehabilitation by
      hand therapy, force, point of action and displacement. The results suggest that
      rehabilitation with traction twice as efficient as that without traction.
      Furthermore, it was found that rehabilitation is possible with calculated force,
      and the force is reproducible by the actuator in the device. 

PMID- 25571193
TI  - FEM numerical model analysis of magnetic nanoparticle tumor heating experiments.
AB  - Iron oxide nanoparticles are currently under investigation as heating agents for
      hyperthermic treatment of tumors. Major determinants of effective heating include
      the biodistribution of magnetic materials, the minimum iron oxide loading
      required to achieve adequate heating, and practically achievable magnetic field
      strengths. These are inter-related criteria that ultimately determine the
      practicability of this approach to tumor treatment. Currently, we lack
      fundamental engineering design criteria that can be used in treatment planning
      and assessment. Coupling numerical models to experimental studies illuminate the
      underlying physical processes and can separate physical processes to determine
      their relative importance. Further, adding thermal damage and cell death process
      to the models provides valuable perspective on the likelihood of successful
      treatment. FEM numerical models were applied to increase the understanding of a
      carefully calibrated series of experiments in mouse mammary carcinoma. The
      numerical models results indicate that tumor loadings equivalent to approximately
      1 mg of Fe3O4 per gram of tumor tissue are required to achieve adequate heating
      in magnetic field strengths of 34 kA/m (rms) at 160 kHz. Further, the models
      indicate that direct intratumoral injection of the nanoparticles results in
      between 1 and 20% uptake in the tissues. 

PMID- 25571194
TI  - Immediate response and cytotoxicity effect on myocardial cells by extracellular
      photosensitization reaction varying irradiance.
AB  - We investigated the extracellular photosensitization effect on myocardial cells
      using talaporfin sodium at various irradiance measuring cell lethality dependence
      on talaporfin sodium concentration and immediate response of intracellular Ca(2+)
      as a fundamental study of the application for tachyarrhythmia treatment. The
      myocardial cell lethality was measured 2 h after the photosensitization reaction
      by WST assay varying the irradiance from 0.12 to 0.66 W/cm(2). The intracellular
      Ca(2+) of myocardial cell was observed during and until 10 min after the
      extracellular photosensitization reaction using fluo-4 AM and a confocal
      microscope varying the irradiance. The linear increasing behavior of the
      myocardial cell lethality with talaporfin sodium concentration was similarly
      obtained in the case of 0.12 and 0.29 W/cm(2) in irradiance. The
      photocytotoxicity was not obtained in the case of 0.46 and 0.66 W/cm(2) in
      irradiance. The time response of necrosis occurrence after the beginning of the
      extracellular photosensitization reaction was decreased with the irradiance
      increasing. We prospect that it may be caused by oxygen depletion in our in vitro
      system using 96 well plate since the irradiance and talaporfin sodium
      concentration were higher comparing the in vitro conditions of the general PDT
      for cancer. 

PMID- 25571195
TI  - A compact microwave patch applicator for hyperthermia treatment of cancer.
AB  - Design and development of a compact microstrip C-type patch applicator for
      hyperthermia treatment of cancer is presented. The patch antenna is optimized for
      resonance at 434 MHz, return loss (S11) better than -15dB and co-polarized
      electric field in tissue. Effect of water bolus thickness on power delivery is
      studied for improved power coupling. Numerical simulations for antenna design
      optimization carried out using EM simulation software, Ansys HFSS((r)), USA were
      experimentally verified. The effective field coverage for the optimized patch
      antenna and experimental results indicate that the compact antenna resonates at
      ISM frequency 434 MHz with better than -15 dB power coupling. 

PMID- 25571196
TI  - Modeling of lung's electrical impedance using fractional calculus for analysis of
      heat generation during RF-ablation.
AB  - Recently, Radio Frequency Ablation (RFA) is becoming a popular therapy for
      various cancers such as liver, breast, or lung cancer. RFA is one kinds of
      thermal therapy. However, it has been often reported about excessive ablation or
      non-ablation due to difficult control of ablation energy. In order to solve these
      difficulties, we have been proposed robotized RF-ablation system for precise
      cancer treatment. We have been tried to control heat energy by control of
      electromagnetic-wave frequency. In this paper, we reported about relation among
      electrical impedance of lung, lung's internal air volumes, and heat energy by use
      of electromagnetic-wave. In case of RFA for lung cancer, heat energy depends on
      electrical impedance and lung's internal air volumes. Electrical impedance has
      the dependence of electromagnetic-wave frequency and the dependence of lung's
      internal air volumes. Therefore, firstly we considered about fractional calculus
      model between lung's internal air volumes and electrical impedance. Secondly, we
      measured electric impedance frequency characteristic of lung with change of
      lung's internal air volumes. The measured and modeled results showed that use of
      fractional calculus realized high accurate model for electrical impedance of
      lung. And, from the results of numerical analysis of heat energy, it is supposed
      that control of electromagnetic-wave frequency has a small effectiveness for lung
      tissue ablation even if lung includes abundant air. 

PMID- 25571197
TI  - Magnetic induction of electroporation: numerical analysis and technical
      limitations.
AB  - Electric fields delivered across biological cells can cause structural and
      functional changes to the cell membrane, such as electroporation. An important
      application of electroporation is in the permeabilization of skin cells.
      Currently these cells are electroporated with contact electrodes. In this study
      we explore the feasibility of using electromagnetic induction for non-contact
      electroporation of skin cells, and the effect of various design parameters on the
      process. We derived a simple analytical solution that lends itself to a
      systematic study of design parameters and verified the solution with a numeric
      solution of the Maxwell equations using finite elements. A short feasibility
      study of the system implementation is done, concluding that there are
      technological limitations that must be met in the future in order to build such a
      device. 

PMID- 25571198
TI  - Estimation of anisotropy coefficient and total attenuation of swine liver at 850
      nm based on a goniometric technique: influence of sample thickness.
AB  - Estimation of optical properties of biologic tissue is crucial for theoretical
      modeling of laser treatments in medicine. Tissue highly absorbs and scatters the
      light between 650 nm and 1300 nm, where the laser provides therapeutic effects.
      Among other properties, the characteristic of biological tissues to scatter the
      light traveling trough, is described by the anisotropy coefficient (g). The
      relationship between g and the distribution of the scattered light at different
      angles is described by Henyey-Greenstein phase function. The measurement of
      angular distribution of scattered light is performed by the goniometric
      technique. This paper describes the estimation of g and attenuation coefficient,
      MUt, of swine liver at 850 nm, performed by an ad hoc designed goniometric-based
      system, where a spectrometer measures intensities of scattered light at fixed
      angles (0 degrees , 30 degrees , 45 degrees , 60, 120 degrees , 135 degrees  and
      150 degrees ). Both one-term and two-term Henyey-Greenstein phase function have
      been employed to estimate anisotropy coefficient for forward (gfs) and backward
      scattering (gbs). Measurements are performed on samples of two thicknesses (60 um
      and 30 urn) to investigate the influence of this factor on g, and repeated 6
      times for each thickness. The estimated values of gfs were 0.947 and 0.951 for
      thickness of 60 MUm and 30 MUm, respectively; the estimations of gfs were -0.498
      and -0.270 for thickness of 60 MUm and 30 MUm, respectively. Moreover, MUt of
      liver has been estimated (i.e., 90+/-20 cm(1)), through Lambert-Beer equation.
      The comparison of our results with data reported in literature encourages the use
      of the ad hoc designed tool for performing experiments on other tissue, and at
      other wavelengths. 

PMID- 25571199
TI  - Assessment of the contralesional corticospinal tract in early-onset pediatric
      hemiplegia: Preliminary findings.
AB  - While pediatric hemiplegia results from a unilateral lesion, the immature state
      of the brain at the time of injury increases the likelihood of observing changes
      in the non-lesioned hemisphere as well. The purpose of this preliminary study was
      to use diffusion tensor imaging to evaluate the contralesional corticospinal
      tracts in individuals with early-onset pediatric hemiplegia. Twelve individuals
      with pediatric hemiplegia and ten age-matched controls underwent diffusion tensor
      imaging (DTI). Corticospinal projections were reconstructed using probabilistic
      tractography for both the lesioned and contralesional side in pediatric
      hemiplegia as well as the dominant and non-dominant sides in control subjects.
      The contralesional tract was found to have decreased white matter integrity
      relative to control subjects. Compared to controls, the contralesional tract also
      showed increased tract volume. The increase in volume suggests the presence of
      ipsilateral corticospinal projections from the contralesional hemisphere that are
      maintained during development to control the paretic extremities. Decreases in
      integrity may be explained by diffuse damage or incomplete maturation. The
      findings of this study support the notion of bilateral motor involvement in
      pediatric hemiplegia, and the need to address bilateral neural changes as well as
      motor deficits in this population. 

PMID- 25571200
TI  - High-density surface EMG decomposition allows for recording of motor unit
      discharge from proximal and distal flexion synergy muscles simultaneously in
      individuals with stroke.
AB  - Analysis of motor unit discharge can provide insight into the neural control of
      movement in healthy and pathological states, but it is typically completed in one
      muscle at a time. For some research investigations, it would be advantageous to
      study motor unit discharge from multiple muscles simultaneously. One such example
      is investigation of the flexion synergy, an abnormal muscle co-activation pattern
      in post-stroke individuals in which activation of shoulder abductors is
      involuntarily coupled with that of elbow and finger flexors. However, limitations
      in available technology have hindered the ability to efficiently extract motor
      unit discharge from multiple muscles simultaneously. In this study, we propose
      the use of high-density surface EMG decomposition from proximal and distal
      flexion synergy muscles (deltoid, biceps, wrist/finger flexors) in combination
      with an isometric joint torque recording device in individuals with chronic
      stroke. This innovative approach provides the ability to efficiently analyze both
      motor units and joint torques that have been simultaneously recorded from the
      shoulder, elbow, and fingers. In preliminary experiments, 3 stroke and 5 control
      participants generated shoulder abduction, elbow flexion, and finger flexion
      torques at 10, 20, 30 and 40% of maximum torque. Motor unit spike trains could be
      extracted from all muscles at each torque level. Mean motor unit firing rates
      were significantly lower in the stroke group than in the control group for all
      three muscles. Within the stroke group, wrist/finger flexor motor units had the
      lowest coefficient of variation. Additionally, modulation of mean firing rates
      across torque levels was significantly impaired in all three paretic muscles. The
      implications of these findings and overall impact of this approach are discussed.

PMID- 25571201
TI  - Objective quantification of upper extremity motor functions in Unified
      Parkinson's Disease Rating Scale Test.
AB  - Two tri-axial accelerometers were placed on the wrists (one on each hand) of the
      patients with Parkinson's disease (PD) and a non-PD control group. Subjects were
      asked to perform three of the upper extremity motor function tasks from the
      Unified Parkinson's Disease Rating Scale (UPDRS) test. The tasks were: 1) finger
      tapping, 2) opening and closing of palms, and 3) pronation-supination movements
      of the forearms. The inertia signals were wirelessly received and stored on a
      computer for further off-line analysis. Various features such as range, standard
      deviation, entropy, time to accomplish the task, and maximum frequency present in
      the signal were extracted and compared. The results showed that among the studied
      population, "standard deviation", "range", "entropy", "time" and "max frequency"
      are the best to worst features, respectively, to distinguish between the non-PD
      and PD subjects. Furthermore, using the mentioned features, it is more probable
      to distinguish between the non-PD and PD subjects from tasks 2 and 3 as opposed
      to task 1. 

PMID- 25571202
TI  - The arm motion detection (AMD) test.
AB  - Stroke can lead to sensory deficits that impair functional control of arm
      movements. Here we describe a simple test of arm motion detection (AMD) that
      provides an objective, quantitative measure of movement perception related
      proprioceptive capabilities in the arm. Seven stroke survivors and thirteen
      neurologically intact control subjects performed the AMD test. In a series of ten
      trials that took less than 15 minutes to complete, participants used a two-button
      user interface to adjust the magnitude of hand displacements produced by a
      horizontal planar robot until the motions were just perceptible (i.e. on the
      threshold of detection). The standard deviation of movement detection threshold
      was plotted against the mean and a normative range was determined from the data
      collected with control subjects. Within this normative space, subjects with and
      without intact proprioception could be discriminated on a ratio scale that is
      meaningful for ongoing studies of degraded motor function. Thus, the AMD test
      provides a relatively fast, objective and quantitative measure of upper extremity
      proprioception of limb movement (i.e. kinesthesia). 

PMID- 25571203
TI  - Quantitative assessment of post-concussion syndrome following mild traumatic
      brain injury using robotic technology.
AB  - Post-Concussion Syndrome (PCS) is a common sequelae of mild Traumatic Brain
      Injury (mTBI). Currently, there is no reliable test to determine which patients
      will develop PCS following an mTBI. As a result, clinicians are challenged to
      identify patients at high risk for subsequent PCS. Hence, there is a need to
      develop an objective test that can guide clinical risk stratification and predict
      the likelihood of PCS at the initial point of care in an Emergency Department
      (ED). This paper presents the results of robotic-assisted neurologic testing
      completed on mTBI patients in the ED and its ability to predict PCS at 3 weeks
      post-injury. Preliminary results show that abnormal proprioception, as measured
      using robotic testing is associated with higher risk of developing PCS following
      mTBI. In this pilot study, proprioceptive measures obtained through robotic
      testing had a 77% specificity (95CI: 46%-94%) and a 64% sensitivity (95CI: 41%
      82%). 

PMID- 25571204
TI  - Submovements during reaching movements after stroke.
AB  - Neurological deficits after cerebrovascular accidents very frequently disrupt the
      kinematics of voluntary movements with the consequent impact in daily life
      activities. Robotic methodologies enable the quantitative characterization of
      specific control deficits needed to understand the basis of functional
      impairments and to design effective rehabilitation therapies. In a group of right
      handed chronic stroke survivors (SS) with right side hemiparesis, intact
      proprioception, and differing levels of motor impairment, we used a robotic
      manipulandum to study right arm function during discrete point-to-point reaching
      movements and reciprocal out-and-back movements to visual targets. We compared
      these movements with those of neurologically intact individuals (NI). We analyzed
      the presence of secondary submovements in the initial (i.e. outward) trajectory
      portion of the two tasks and found that the SS with severe impairment (FM < 30)
      presented arm submovements that differed notably not only from NI but also from
      those of SS with moderate arm impairment (FM 30-50). Therefore the results of
      this pilot study suggest that in SS arm kinematics vary significantly across
      differing levels of motor impairment. Our results support the development of
      rehabilitation therapies carefully tailored to each individual stroke survivor.

PMID- 25571205
TI  - Investigation of photoplethysmography and near infrared spectroscopy for the
      assessment of tissue blood perfusion.
AB  - Pulse Oximetry (PO) and Near Infrared Spectroscopy (NIRS) are among the most
      widely adopted optical techniques for the assessment of tissue perfusion. PO
      estimates arterial oxygen saturation (SpO2) by exploiting light attenuations due
      to pulsatile arterial blood (AC) and constant absorbers (DC) at two different
      wavelengths. NIRS processes the attenuations of at least two wavelengths to
      calculate concentrations of Deoxygenated ([HHb]), Oxygenated ([HbO2]), Total
      Haemoglobin ([tHb]) and Tissue Oxygenation Index (TOI). In this work we present
      the development and evaluation of a reflectance PPG probe and processing system
      for the assessment of tissue perfusion. The system adopts both Pulse Oximetry and
      NIRS principles to calculate SpO2, [HHb], and [HbO2] and [tHb]. The system has
      been evaluated on the forearm of 10 healthy volunteers during cuff-induced
      vascular occlusions. The presented system was able to estimate SpO2, [HHb],
      [HbO2] and [tHb], showing good agreement with state-of-the-art NIRS and
      conventional PO. 

PMID- 25571206
TI  - Heart rate estimation from FBG sensors using cepstrum analysis and sensor fusion.
AB  - This paper presents a method of estimating heart rate from arrays of fiber Bragg
      grating (FBG) sensors embedded in a mat. A cepstral domain signal analysis
      technique is proposed to characterize Ballistocardiogram (BCG) signals. With this
      technique, the average heart beat intervals can be estimated by detecting the
      dominant peaks in the cepstrum, and the signals of multiple sensors can be fused
      together to obtain higher signal to noise ratio than each individual sensor.
      Experiments were conducted with 10 human subjects lying on 2 different postures
      on a bed. The estimated heart rate from BCG was compared with heart rate ground
      truth from ECG, and the mean error of estimation obtained is below 1 beat per
      minute (BPM). The results show that the proposed fusion method can achieve
      promising heart rate measurement accuracy and robustness against various sensor
      contact conditions. 

PMID- 25571207
TI  - Alveolar air volatile organic compound extractor for clinical breath sampling.
AB  - Alveolar air Volatile Organic Compound (VOC) extractor is a handheld breath
      sampling device for clinical breath analysis. The device consists two main
      components: (1) An alveolar air separator, (2) A VOC extractor. The alveolar air
      separator splits exhaled air based on total exhaled air volume directing alveolar
      air towards the VOC extractor and dead space air to into an exhaust channel. The
      VOC extractor collects the VOCs from alveolar air into a modified Sold Phase
      Micro Extraction (SPME) filament. Feasibility of using the SPME filament to
      collect a quantifiable breath sample directly from exhaled breath is
      experimentally validated. Exhaled breath acetone is quantified using alveolar air
      VOC extractor and a GC/MS system. 

PMID- 25571208
TI  - Toward using alpha and theta brain waves to quantify programmer expertise.
AB  - Empirical studies of programming language learnability and usability have thus
      far depended on indirect measures of human cognitive performance, attempting to
      capture what is at its essence a purely cognitive exercise through various
      indicators of comprehension, such as the correctness of coding tasks or the time
      spent working out the meaning of code and producing acceptable solutions.
      Understanding program comprehension is essential to understanding the inherent
      complexity of programming languages, and ultimately, having a measure of mental
      effort based on direct observation of the brain at work will illuminate the
      nature of the work of programming. We provide evidence of direct observation of
      the cognitive effort associated with programming tasks, through a carefully
      constructed empirical study using a cross-section of undergraduate computer
      science students and an inexpensive, off-the-shelf brain-computer interface
      device. This study presents a link between expertise and programming language
      comprehension, draws conclusions about the observed indicators of cognitive
      effort using recent cognitive theories, and proposes directions for future work
      that is now possible. 

PMID- 25571209
TI  - Monitoring respiration and cardiac activity during sleep using microbend fiber
      sensor: A clinical study and new algorithm.
AB  - We report results from a clinical trial for monitoring respiration and cardiac
      activity of patients during sleep using microbend fiber sensor. This sensor is
      used to acquire respiratory and heart beat information. We have collected
      reference data from standard Polysomnography and data from microbend fiber sensor
      on 22 patients. A new algorithm is developed to calculate breathing rate and
      heart rate simultaneously. The Bland-Altman analysis demonstrates the
      measurements have good accuracy for monitoring purposes compared with the
      standard Polysomnography. An accuracy of 1.06bpm for breathing rate and 3.32bpm
      for heart rate has been validated for 30s averaging time although there were
      significant signal distortions under sleep conditions. 

PMID- 25571210
TI  - Application of wireless inertial measurement units and EMG sensors for studying
      deglutition - Preliminary results.
AB  - Different types of sensors are being used to study deglutition and mastication.
      These often suffer from problems related to portability, cost, reliability,
      comfort etc. that make it difficult to use for long term studies. An inertial
      measurement based sensor seems a good fit in this application; however its use
      has not been explored much for the specific application of deglutition research.
      In this paper, we present a system comprised of an IMU and EMG sensor that are
      integrated together as a single system. With a preliminary experiment, we
      determine that the system can be used for measuring the head-neck posture during
      swallowing in addition to other parameters during the swallowing phase. The EMG
      sensor may not always be a reliable source of physiological data especially for
      small clustered muscles like the ones responsible for swallowing. In this case,
      we explore the possibility of using gyroscopic data for the recognition of
      deglutition events. 

PMID- 25571211
TI  - Toward seamless wearable sensing: Automatic on-body sensor localization for
      physical activity monitoring.
AB  - Mobile wearable sensors have demonstrated great potential in a broad range of
      applications in healthcare and wellness. These technologies are known for their
      potential to revolutionize the way next generation medical services are supplied
      and consumed by providing more effective interventions, improving health
      outcomes, and substantially reducing healthcare costs. Despite these potentials,
      utilization of these sensor devices is currently limited to lab settings and in
      highly controlled clinical trials. A major obstacle in widespread utilization of
      these systems is that the sensors need to be used in predefined locations on the
      body in order to provide accurate outcomes such as type of physical activity
      performed by the user. This has reduced users' willingness to utilize such
      technologies. In this paper, we propose a novel signal processing approach that
      leverages feature selection algorithms for accurate and automatic localization of
      wearable sensors. Our results based on real data collected using wearable motion
      sensors demonstrate that the proposed approach can perform sensor localization
      with 98.4% accuracy which is 30.7% more accurate than an approach without a
      feature selection mechanism. Furthermore, utilizing our node localization
      algorithm aids the activity recognition algorithm to achieve 98.8% accuracy (an
      increase from 33.6% for the system without node localization). 

PMID- 25571212
TI  - A smartphone application to evaluate technology adoption and usage in persons
      with dementia.
AB  - Dementia affects a proportionally large number of the older population,
      presenting a set of symptoms that cause cognitive decline and negatively affect
      quality of life. Technology offers an assistive role for some of these symptoms,
      specifically in addressing forgetfulness. Current works have explored the
      benefits of reminding technology, which whilst useful is only effective for those
      who adopt the technology. Therefore it is of merit to establish the individual
      parameters that characterize an adopter and non-adopter, to better target future
      interventions and their deployment. To aid the collection of this data a
      smartphone app was developed for persons with dementia. It has been designed as
      both a reminder application to help those with dementia accommodate their
      forgetfulness and a data collection tool to log usage and compliance with
      reminders. The app has been evaluated by a pre-pilot cohort (n=9) and was found
      to have a mean reminder acknowledgement of 73.09%. 

PMID- 25571213
TI  - An integrated model for cognitive behavioural therapy for mobile diabetes self
      management system.
AB  - There is increasing clinical evidence that behavioural change theories can help
      diabetic patients with their diabetic management in providing better education
      and a healthy lifestyle. In recent years, Cognitive Behavioural Therapy (CBT) has
      been increasingly used as a key psychological method for studies of behavioural
      changes for diabetes patients. However, to date, there is no extensive study that
      addresses the challenges and opportunities on applying CBT models within the
      mobile diabetes management cycle of care. In this paper, we present a review of
      the current status of CBT in diabetes management and propose a model for the
      implementation of CBT Therapy into a mobile diabetes management system by using
      smart mobile phone technologies. 

PMID- 25571214
TI  - Respiratory rate assessment from photoplethysmographic imaging.
AB  - We present a study investigating the suitability of a respiratory rate estimation
      algorithm applied to photoplethysmographic imaging on a mobile phone. The
      algorithm consists of a cascade of previously developed signal processing methods
      to detect features and extract respiratory induced variations in
      photoplethysmogram signals to estimate respiratory rate. With custom-built
      software on an Android phone (Camera Oximeter), contact photoplethysmographic
      imaging videos were recorded using the integrated camera from 19 healthy adults
      breathing spontaneously at respiratory rates between 6 and 40 breaths/min.
      Capnometry was simultaneously recorded to obtain reference respiratory rates. Two
      hundred and ninety-eight Camera Oximeter recordings were available for analysis.
      The algorithm detected 22 recordings with poor photoplethysmogram quality and 46
      recordings with insufficient respiratory information. Of the 232 remaining
      recordings, a root mean square error of 5.9 breaths/min and a median absolute
      error of 2.3 breaths/min was obtained. The study showed that it is feasible to
      estimate respiratory rates by placing a finger on a mobile phone camera, but that
      it becomes increasingly challenging at respiratory rates higher than 20
      breaths/min. 

PMID- 25571215
TI  - Peak misdetection in heart-beat-based security: Characterization and tolerance.
AB  - The Inter-Pulse-Interval (IPI) of heart beats has previously been suggested for
      security in mobile health (mHealth) applications. In IPI-based security, secure
      communication is facilitated through a security key derived from the time
      difference between heart beats. However, there currently exists no work which
      considers the effect on security of imperfect heart-beat (peak) detection. This
      is a crucial aspect of IPI-based security and likely to happen in a real system.
      In this paper, we evaluate the effects of peak misdetection on the security
      performance of IPI-based security. It is shown that even with a high peak
      detection rate between 99.9% and 99.0%, a significant drop in security
      performance may be observed (between -70% and -303%) compared to having perfect
      peak detection. We show that authenticating using smaller keys yields both
      stronger keys as well as potentially faster authentication in case of imperfect
      heart beat detection. Finally, we present an algorithm which tolerates the effect
      of a single misdetected peak and increases the security performance by up to
      155%. 

PMID- 25571216
TI  - Detection of hypertensive retinopathy using vessel measurements and textural
      features.
AB  - Features that indicate hypertensive retinopathy have been well described in the
      medical literature. This paper presents a new system to automatically classify
      subjects with hypertensive retinopathy (HR) using digital color fundus images.
      Our method consists of the following steps: 1) normalization and enhancement of
      the image; 2) determination of regions of interest based on automatic location of
      the optic disc; 3) segmentation of the retinal vasculature and measurement of
      vessel width and tortuosity; 4) extraction of color features; 5) classification
      of vessel segments as arteries or veins; 6) calculation of artery-vein ratios
      using the six widest (major) vessels for each category; 7) calculation of mean
      red intensity and saturation values for all arteries; 8) calculation of amplitude
      modulation frequency-modulation (AM-FM) features for entire image; and 9)
      classification of features into HR and non-HR using linear regression. This
      approach was tested on 74 digital color fundus photographs taken with TOPCON and
      CANON retinal cameras using leave-one out cross validation. An area under the ROC
      curve (AUC) of 0.84 was achieved with sensitivity and specificity of 90% and 67%,
      respectively. 

PMID- 25571217
TI  - Assessment of vessel tortuosity in retinal images of preterm infants.
AB  - Diagnosis of plus disease is crucial for timely treatment and management of
      retinopathy of prematurity. An indicator of the presence of plus disease is an
      increase in the tortuosity of blood vessels in the retina. In this work, we
      propose a new angle-variation-based measure for quantification of tortuosity in
      retinal fundus images of preterm infants. The methods include the use of Gabor
      filters to detect vessels as well as to obtain their orientation at each pixel.
      Morphological image processing methods are used to obtain a skeleton image of the
      vessels for measurement of tortuosity. Out of 11 vessel segments, marked by an
      expert ophthalmologist as showing high levels of tortuosity due to plus disease,
      all were correctly identified using the proposed methods. 

PMID- 25571219
TI  - Local patch reconstruction framework for optic cup localization in glaucoma
      detection.
AB  - Optic cup localization/segmentation has attracted much attention from medical
      imaging researchers, since it is the primary image component clinically used for
      identifying glaucoma, which is a leading cause of blindness. In this work, we
      present an optic cup localization framework based on local patch reconstruction,
      motivated by the great success achieved by reconstruction approaches in many
      computer vision applications recently. Two types of local patches, i.e. grids and
      superpixels are used to show the variety, generalization ability and robustness
      of the proposed framework. Tested on the ORIGA clinical dataset, which comprises
      of 325 fundus images from a population-based study, both implementations under
      the proposed frameworks achieved higher accuracy than the state-of-the-art
      techniques. 

PMID- 25571218
TI  - An experimental assessment of five indices of retinal vessel tortuosity with the
      RET-TORT public dataset.
AB  - We compare the performance of five indices of retinal vessel tortuosity against
      sampling rates of vessel centerlines. We consider distance measure, tortuosity
      density, two curvature-based measures, and a recently introduced slope-chain
      coding for general curves, never before assessed comparatively with retinal
      vessels. To enable replication of our results, we use the public dataset for
      retinal tortuosity, RET-TORT. We find that (1) the tortuosity density index
      offers good performance overall, but is not always the best performer; (2)
      curvature-based methods are the best if high-frequency resampling is possible,
      but (3) are the most sensitive to variations of the number of samples; (4) slope
      chain coding performs best at low sampling rates, but the length of the linear
      elements must be chosen carefully. In general, performance may vary considerably
      with resampling, suggesting that the choice of a tortuosity index for clinical
      inference requires attention to numerical details, and ideally standardization
      thereof.

PMID- 25571220
TI  - A fully-automatic fast segmentation of the sub-basal layer nerves in corneal
      images.
AB  - Corneal nerves changes have been linked to damage caused by surgical
      interventions or prolonged contact lens wear. Furthermore nerve tortuosity has
      been shown to correlate with the severity of diabetic neuropathy. For these
      reasons there has been an increasing interest on the analysis of these
      structures. In this work we propose a novel, robust, and fast fully automatic
      algorithm capable of tracing the sub-basal plexus nerves from human corneal
      confocal images. We resort to logGabor filters and support vector machines to
      trace the corneal nerves. The proposed algorithm traced most of the corneal
      nerves correctly (sensitivity of 0.88 +/- 0.06 and false discovery rate of 0.08
      +/- 0.06). The displayed performance is comparable to a human grader. We believe
      that the achieved processing time (0.661 +/- 0.07 s) and tracing quality are
      major advantages for the daily clinical practice. 

PMID- 25571221
TI  - Automatic montaging of corneal sub-basal nerve images for the composition of a
      wide-range mosaic.
AB  - We present and discuss a computerized system able to provide a wide-range mosaic
      of the sub-basal nerve layer of central cornea, built from several images
      acquired in-vivo with confocal microscopy. The montage is performed by a fast,
      reliable and fully automatic computerized system that does not require any
      expedient or manual adjustment during the acquisition process. The resulting
      mosaic provides a large high quality image, which should significantly aid
      clinicians in evaluating and assessing in a more reliable way the pathologic
      signs of interest. 

PMID- 25571222
TI  - Continuous wavelet application for the assessment of neural potential interaction
      during time discrimination task.
AB  - The aim of the paper is to assess the interaction of the neural potentials during
      a time discrimination psychoacoustic task. Ten subjects participated in the
      experiment and were asked about the equality of two acoustic pulses: one
      reference of 500ms and one trial that varied from 420ms to 620ms. During the
      experimental procedure, Electroencephalogram (EEG) and Event Related Potential
      (ERP) signals were recorded. The analysis combines results from Continuous
      Wavelet signal processing and subjects responses which were analyzed based on
      psychoacoustic theory. The Wavelet Coherence metric index is employed to assess
      the interaction of neural potentials. The results indicate the points at which
      the duration of the trial pulse is equal to 560ms and 460ms as the minimum and
      maximum of the Wavelet Coherence metric index, respectively. This observation is
      valid in most electrodes, for all basic EEG rhythms, revealing in parallel the
      differentiation of the gamma rhythm, in relation to the others. These maximum and
      minimum values are correlated to the Just Noticeable Difference (JND) in pulses
      duration, calculated by the psychoacoustic analysis. 

PMID- 25571223
TI  - Neural potentials disorder during differential psychoacoustic experiment
      evaluated by discrete wavelet analysis.
AB  - The aim of the paper is the assessment of neural potentials disorder during a
      differential sensitivity psychoacoustic procedure. Ten volunteers were asked to
      compare the duration of two acoustic pulses: one reference with stable duration
      of 500 ms and one trial which varied from 420 ms to 620 ms. During the
      discrimination task, Electroencephalogram (EEG) and Event Related Potential (ERP)
      signals were recorded. The mean Relative Wavelet Energy (mRWE) and the normalized
      Shannon Wavelet Entropy (nSWE) are computed based on the Discrete Wavelet
      analysis. The results are correlated to the data derived by the psychoacoustic
      analysis on the volunteers responses. In most of the electrodes, when the
      duration of the trial pulse is 460 ms and 560 ms, there is an increase and a
      decrease in nSWE value, respectively, which is determined mostly by the mRWE in
      delta rhythm. These extrema are correlated to the Just Noticeable Difference
      (JND) in pulses duration, calculated by psychoacoustic analysis. The dominance of
      delta rhythm during the whole auditory experiment is noteworthy. The lowest
      values of nSWE are noted in temporal lobe. 

PMID- 25571224
TI  - On the effect of subliminal priming on subjective perception of images: a machine
      learning approach.
AB  - The research presented in this article investigates the influence of subliminal
      prime words on peoples' judgment about images, through electroencephalograms
      (EEGs). In this cross domain priming paradigm, the participants are asked to rate
      how much they like the stimulus images, on a 7-point Likert scale, after being
      subliminally exposed to masked lexical prime words, with EEG recorded
      simultaneously. Statistical analysis tools are used to analyze the effect of
      priming on behavior, and machine learning techniques to infer the primes from
      EEGs. The experiment reveals strong effects of subliminal priming on the
      participants' explicit rating of images. The subjective judgment affected by the
      priming makes visible change in event-related potentials (ERPs); results show
      larger ERP amplitude for the negative primes compared with positive and neutral
      primes. In addition, Support Vector Machine (SVM) based classifiers are proposed
      to infer the prime types from the average ERPs, which yields a classification
      rate of 70%. 

PMID- 25571225
TI  - A high frequency steady-state visually evoked potential based brain computer
      interface using consumer-grade EEG headset.
AB  - This work evaluates a possibility of creating a high-frequency, SSVEP-based brain
      computer interface using a low cost EEG recording hardware - an Emotiv EEG Neuro
      headset. Both above aspects are crucial to enable deploying the BCI technology in
      the consumer market. High frequencies can be used to create a non-tiring and more
      pleasant interface. Commercial EEG systems, as the Emotiv EEG, although
      demonstrating large underperformance, are much more affordable than standard,
      clinical-grade EEG amplifiers. A system classifying between two stimuli and rest
      is designed and tested in two experiments: on five and ten subject respectively.
      First, the accuracy of the system is compared for frequencies in lower range
      (17Hz, 19Hz, 23Hz, 25Hz) and higher range (31Hz, 33Hz, 37Hz, 40Hz). The mean
      online accuracy is 80%+/-15% for the former and 67%+/-12% for the latter. Second,
      a more thorough investigation is done by evaluating the system for frequencies
      within a set of 35Hz-40Hz. Although the mean accuracy, 64% +/- 22%, is relatively
      low, most of the users were able to achieve satisfying accuracy, with the mean
      reaching 82%+/-5%, which would allow for an efficient, and yet pleasant, usage of
      the BCI system. In each case a user dependent approach is applied, with a
      calibration session lasting about five minutes. EEG feature extraction is done
      using common spatial pattern (CSP) filtering, canonical correlation analysis
      (CCA), and linear discrimination analysis (LDA). 

PMID- 25571226
TI  - Information flow and coherence of EEG during awake, meditation and drowsiness.
AB  - A comparison of coupling (information flow) and coherence (connectedness) of the
      brain regions between human awake, meditation and drowsiness states was carried
      out in this study. The Directed Transfer Function (DTF) method was used to
      estimate the coupling or brain's flow of information between different regions
      during each condition. Welch and Minimum Variance Distortionless Response (MVDR)
      methods were utilised to estimate the coherence between brain areas. Analysis was
      conducted using the EEG data of 30 subjects (10 awake, 10 drowsiness and 10
      meditating) with 6 EEG electrodes. The EEG data was recorded for each subject
      during 5 minutes baseline and 15 minutes of three specific conditions (awake,
      meditation or drowsiness). Statistical analysis was carried out which consisted
      of the Kruskal-Wallis (KW) non-parametric analysis of variance followed by post
      hoc tests with Bonferroni alpha-correction. The results of this study revealed
      that a change in external awareness led to substantial differences in the
      spectral profile of the brain's information flow as well as it's connectedness. 

PMID- 25571227
TI  - Detection of K-complexes based on the wavelet transform.
AB  - Sleep scoring needs computational assistance to reduce execution time and to
      assure high quality. In this pilot study a semi-automatic K-Complex detection
      algorithm was developed using wavelet transformation to identify pseudo-K
      Complexes and various feature thresholds to reject false positives. The algorithm
      was trained and tested on sleep EEG from two databases to enhance its general
      applicability. When testing on data from subjects from the DREAMS(c) database, a
      mean true positive rate of 74 % and a positive predictive value of 65 % were
      achieved. After adjusting a few thresholds to adapt to the second database, the
      Danish Center for Sleep Medicine, a similar performance was achieved. The
      algorithm performs at the level of the State of the Art and surpasses the inter
      rater agreement rate. 

PMID- 25571228
TI  - Resting state and task-related brain dynamics supporting insight.
AB  - Problems can be solved in a variety of ways. One might systematically evaluate a
      known space of possible solutions until the right one is found. Alternatively, it
      may prove necessary to enlarge or restructure the expected problem space - so
      called "thinking outside the box." This approach can yield an experience of
      unexpected insight or feeling of Aha!. Current challenges to understanding this
      phenomenon from a neurocognitive perspective include the vast diversity of
      problem domains and time scales for solutions. Whereas the subjective suddenness
      of an "Aha!" moment may lead to the impression that insight must be precipitated
      by a set of discrete, short-lived neural events, this report outlines research
      revealing that even before a problem is presented, scalp-recorded measures of
      resting or baseline brain states are linked with future performance and
      likelihood of experiencing insight during the search for a solution.
      Additionally, this study also shows that compared to more systematic problem
      solving approaches, insight is accompanied by differences in cortical and likely
      cognitive engagement that are detectable throughout much of the problem solving
      phase, rather than being confined to a distinct interval immediately preceding
      the dawn of a solution. These findings are important for the development of
      therapies targeting problem solving and reasoning skills, such as those used in
      cognitive training interventions to mitigate the effects of cognitive decline. 

PMID- 25571229
TI  - Adaptive BCI based on software agents.
AB  - The selection of features is generally the most difficult field to model in BCIs.
      Therefore, time and effort are invested in individual feature selection prior to
      data set training. Another great difficulty regarding the model of the BCI
      topology is the brain signal variability between users. How should this topology
      be in order to implement a system that can be used by large number of users with
      an optimal set of features? The proposal presented in this paper allows for
      obtaining feature reduction and classifier selection based on software agents.
      The software agents contain Genetic Algorithms (GA) and a cost function. GA used
      entropy and mutual information to choose the number of features. For the
      classifier selection a cost function was defined. Success rate and Cohen's Kappa
      coefficient are used as parameters to evaluate the classifiers performance. The
      obtained results allow finding a topology represented as a neural model for an
      adaptive BCI, where the number of the channels, features and the classifier are
      interrelated. The minimal subset of features and the optimal classifier were
      obtained with the adaptive BCI. Only three EEG channels were needed to obtain a
      success rate of 93% for the BCI competition III data set IVa. 

PMID- 25571230
TI  - SSVEP-modulation by covert and overt attention: Novel features for BCI in
      attention neuro-rehabilitation.
AB  - In this pilot study the effect of attention (covert and overt) on the signal
      detection and classification of steady-state visual-evoked potential (SSVEP) were
      investigated. Using the SSVEP-based paradigm, data were acquired from 4 subjects
      using 3 scalp electroencephalography (EEG) electrodes located on the visual area.
      Subjects were instructed to perform the attention task in which they attended
      covertly or overtly to either of the stimuli flickering with different
      frequencies (6, 7, 8 and 9Hz). We observed a decrease in signal power in covert
      compared to the overt attention. However, there was a consistent pattern in
      covert attention causing an increase in the power of the 2(nd) harmonic of the
      attended frequency. Encouraging results of this preliminary study indicates that
      it can be adapted and implemented in the brain-computer interface (BCI) system
      which could potentially be used as a neuro-rehabilitation tool for individuals
      with attention deficit. 

PMID- 25571231
TI  - Transforming artifact to signal: A wavelet-based algorithm for quantifying
      neonatal movement.
AB  - In neonatal research, physiological signals are often degraded by an artifact
      generated by movement of the infant. Portions of these movement embedded signals
      are commonly excluded in the analysis of the relevant physiological signal.
      However, movement may be a significant marker of physiological development of the
      infant. Here we present results from a wavelet-based algorithm that quantifies
      neonatal movement, using recordings from the pulse plethysmograph. We suggest
      that movement-induced artifactual signal can yield important physiological
      information regarding neonatal physiology. 

PMID- 25571232
TI  - A novel method for the automatic segmentation of activity data from a wrist worn
      device: Preliminary results.
AB  - Activity monitoring is used in a number of fields in order to assess the physical
      activity of the user. Applications include health and well-being, rehabilitation
      and enhancing independent living. Data are often gathered from multiple
      accelerometers and analysis focuses on multi-parametric classification. For
      longer term monitoring this is unsuitable and it is desirable to develop a method
      for the precise analysis of activity data with respect to time. This paper
      presents the initial results of a novel approach to this problem which is capable
      of segmenting activity data collected from a single accelerometer recording
      naturalized activity. 

PMID- 25571233
TI  - Time-frequency visualization of alcohol withdrawal tremors.
AB  - In this paper, we propose a signal processing method of assessing the severity
      tremors caused by alcohol withdrawal (AW) syndrome. We have developed an iOS
      application to calculate the Clinical Institute Withdrawal Assessment (CIWA)
      score which captures iPod movements using the built-in accelerometer in order to
      reliably estimate the tremor severity component of the score. We report on the
      characteristics of AW tremor, the accuracy of electronic assessment of tremor
      compared to expert clinician assessment, and the potential for using signal
      processing assessment to differentiate factitious from real tremor in patients
      seen in the emergency department, as well as in nurses mimicking a tremor. Our
      preliminary results are based on 84 recordings from 61 subjects (49 patients, 12
      nurses). In general we found a linear relationship between energy measured by the
      accelerometer (in the 4.4-10 Hz range) and the expert rating of tremor severity.
      Additionally, we demonstrate that 75% of the recordings from patients with actual
      AW syndrome had a mean peak frequency higher than 7 Hz whereas only 17% of the
      nurses' factitious tremors were above 7 Hz, suggesting that tremor above 7 Hz
      could be a potential discriminator of real versus factitious tremors. 

PMID- 25571234
TI  - Deconvolution of high rate flicker electroretinograms.
AB  - Flicker electroretinograms are steady-state electroretinograms (ERGs) generated
      by high rate flash stimuli that produce overlapping periodic responses. When a
      flash stimulus is delivered at low rates, a transient response named flash ERG
      (FERG) representing the activation of neural structures within the outer retina
      is obtained. Although FERGs and flicker ERGs are used in the diagnosis of many
      retinal diseases, their waveform relationships have not been investigated in
      detail. This study examines this relationship by extracting transient FERGs from
      specially generated quasi steady-state flicker and ERGs at stimulation rates
      above 10 Hz and similarly generated conventional flicker ERGs. The ability to
      extract the transient FERG responses by deconvolving flicker responses to
      temporally jittered stimuli at high rates is investigated at varying rates. FERGs
      were obtained from seven normal subjects stimulated with LED-based displays,
      delivering steady-state and low jittered quasi steady-state responses at five
      rates (10, 15, 32, 50, 68 Hz). The deconvolution method enabled a successful
      extraction of "per stimulus" unit transient ERG responses for all high
      stimulation rates. The deconvolved FERGs were used successfully to synthesize
      flicker ERGs obtained at the same high stimulation rates. 

PMID- 25571235
TI  - Analysis of cochlear implant artifact removal techniques using the continuous
      wavelet transform.
AB  - When patients with cochlear implants (CI) undergo cortical auditory evoked
      potential (CAEP) tests to evaluate their hearing, a large electrical artifact
      introduced by the CI obscures the relevant information in the signal. Several
      methods have been developed for the purpose of removing the CI artifact; however,
      there is no gold standard (i.e., patient's auditory response before the CI) to
      assess the effectiveness of these methods in terms of successful removal of
      artifact. To address this crucial shortcoming, we employ time-frequency (TF)
      signal representation (i.e., continuous wavelet transform (CWT)) to evaluate the
      effectiveness of two recent CI removal techniques, known as the subtraction and
      polynomial methods. Our results show that polynomial method consistently
      outperforms the subtraction method in the presence of tone stimulus. These
      results also indicate a possible CWT-based method for removing the CI artifact
      from a speech stimuli response, which the subtraction and polynomial methods
      cannot do. 

PMID- 25571236
TI  - Spike detection and sorting using PARAFAC2 method.
AB  - In this contribution we introduce the Parallel Factor 2 (PARAFAC2) analysis as a
      novel method for the simultaneous detection and classification of neural action
      potentials. In order to measure these action potentials (spike signals), stem
      cell derived neuronal cells are cultivated on the surface of a Micro Electrode
      Array (MEA). Here, the neuronal cells produce ion currents, which can be measured
      as extracellular electric potentials. Whenever a cell or a group of cells
      produces ion currents, either spontaneously or evoked by a stimulus, a spike
      signal can be measured by the electrodes of the MEA. Stimulated cells produce
      spikes and groups of spikes (bursts) which propagate in space over the MEA. In
      the recorded data, different source types (e.g., cells which respond directly to
      external stimuli and cells which are triggered by other neural cells) are
      characterized by different spike shapes. The proposed PARAFAC2 method is able to
      separate these spike shapes (sources) in time, frequency and space (channels)
      enabling an improved performance in noisy scenarios. Furthermore, PARAFAC2 allows
      for a causality analysis on the measured spike signals (i.e. the identification
      of different signal paths). Thereby, the PARAFAC2 decomposition is able to
      exploit the multi-dimensional structure of the MEA data. 

PMID- 25571237
TI  - Pediatric heart sound segmentation using hidden Markov model.
AB  - Recent advances in technology have enabled automatic cardiac auscultation using
      digital stethoscopes. This in turn creates the need for development of algorithms
      capable of automatic segmentation of heart sounds. Pediatric heart sound
      segmentation is a challenging task due to various confounding factors including
      the significant influence of respiration on children's heart sounds. The current
      work investigates the application of homomorphic filtering and Hidden Markov
      Model for the purpose of segmenting pediatric heart sounds. The efficacy of the
      proposed method is evaluated on the publicly available Pascal Challenge dataset
      and its performance is compared with those of three other existing methods. The
      results show that our proposed method achieves an accuracy of 92.4%+/-1.1% and
      93.5%+/-1.1% in identifying the first and second heart sound components,
      respectively, and is superior to three other existing methods in terms of
      accuracy or computational complexity. 

PMID- 25571238
TI  - Noninvasive blood pressure and the second heart sound analysis.
AB  - Heart sound characteristics are linked to blood pressure, and its interpretation
      is important for detection of cardiovascular disease. In this study, heart
      sounds' auscultation, acquired from children patients (27 patients, 10.2+/-3.9
      years, 35.7+/-20.8 kg, 132.3+/-25.5 cm), were automatically segmented to extract
      the two main components: the first sound (S1) and the second sound (S2).
      Following, a set of time, frequency, and wavelet based features, were extracted
      from the S2, and analyzed in relation to the noninvasive cuff-based measures of
      blood pressure (mean blood pressure of 78+/-8.8 mmHg). A multivariate regression
      analysis was performed for each S2 feature set to determine which features better
      related to the blood pressure measurements. The best results, in the leave-one
      out evaluation, were obtained using the frequency features set, with a MAE of
      6.08 mmHg, a MAPE of 7.85%, and a ME of 0.31 mmHg, in the estimation of the mean
      blood pressure. 

PMID- 25571239
TI  - Developing time-frequency features for prediction of the recurrence of atrial
      fibrillation after electrical cardioversion therapy.
AB  - External electrical cardioversion has been used as a therapeutic option to
      terminate atrial fibrillation (AF) and restore sinus rhythm (SR). However,
      identifying patients who would benefit from this therapy is still an active area
      of research. In this study, we develop new time-frequency features to
      characterize the atrial activity (AA) and to predict the success of electrical
      cardioversion therapy by identifying the AF patients who will maintain SR in the
      long term. New features are extracted from the surface AA using a matching
      pursuit (MP) decomposition with various combinations of wavelet families. The
      performance of the features is validated using a dataset of AF patients who
      underwent electrical cardioversion therapy. Results indicate that the developed
      features are significantly (p-value <; 0.05) correlated with SR maintenance which
      suggests that the MP decomposition captures detailed morphological information of
      AA that may potentially be used to guide the therapy of AF patients. 

PMID- 25571240
TI  - Ambulatory pain evaluation based on heart rate variability analysis: Application
      to physical therapy.
AB  - Pain assessment is critical for efficient pain management. Clinicians usually use
      self-report or behavioral pain scales. In practice, the choice of the most
      adaptive scale depends on several parameters like the clinical context, the
      patient consciousness or its age, but all evaluation scales are known to be more
      or less subjective and to present high inter and intra individual variability.
      Recently, several innovative medical devices have been developed in order to
      provide to the clinicians a physiological measure of pain. These technologies are
      mainly used for the continuous monitoring of patients in intensive care or during
      surgery. As an example, we have developed a heart rate variability analysis based
      technology for analgesia/nociception monitoring in patients undergoing surgery
      under general anesthesia. Even if this technology is now used in other clinical
      settings, the resulting device presents some mobility constraints. In this paper,
      we describe the adaptation of this technology to the ambulatory pain evaluation
      and its clinical validation in the particular context of physical therapy. In the
      frame of this validation, we showed the device usability and efficiency for pain
      evaluation during physical therapy sessions. 

PMID- 25571241
TI  - Learning a cost function for microscope image segmentation.
AB  - Quantitative analysis of microscopy images is increasingly important in clinical
      researchers' efforts to unravel the cellular and molecular determinants of
      disease, and for pathological analysis of tissue samples. Yet, manual
      segmentation and measurement of cells or other features in images remains the
      norm in many fields. We report on a new system that aims for robust and accurate
      semi-automated analysis of microscope images. A user interactively outlines one
      or more examples of a target object in a training image. We then learn a cost
      function for detecting more objects of the same type, either in the same or
      different images. The cost function is incorporated into an active contour model,
      which can efficiently determine optimal boundaries by dynamic programming. We
      validate our approach and compare it to some standard alternatives on three
      different types of microscopic images: light microscopy of blood cells, light
      microscopy of muscle tissue sections, and electron microscopy cross-sections of
      axons and their myelin sheaths. 

PMID- 25571242
TI  - Segmentation of occluded hematopoietic stem cells from tracking.
AB  - Image sequences of live proliferating cells often contain visual ambiguities that
      are difficult even for human domain experts to resolve. Here we present a new
      approach to analyzing image sequences that capture the development of clones of
      hematopoietic stem cells (HSCs) from live cell time lapse microscopy. The HSCs
      cannot survive long term imaging unless they are cultured together with a
      secondary cell type, OP9 stromal cells. The HSCs frequently disappear under the
      OP9 cell layer, making segmentation difficult or impossible from a single image
      frame, even for a human domain expert. We have developed a new approach to the
      segmentation of HSCs that captures these occluded cells. Starting with an a
      priori segmentation that uses a Monte Carlo technique to estimate the number of
      cells in a clump of touching cells, we proceed to track and lineage the image
      data. Following user validation of the lineage information, an a posteriori
      resegmentation step utilizing tracking results delineates the HSCs occluded by
      the OP9 layer. Resegmentation has been applied to 3031 occluded segmentations
      from 77 tracks, correctly recovering over 84% of the occluded segmentations. 

PMID- 25571243
TI  - A fully automated method for spinal canal detection in computed tomography
      images.
AB  - This work presents a new automated method for spinal canal detection in Computed
      Tomography (CT) images. It uses both 2D and 3D information and the algorithm
      extracts the spinal canal automatically. The procedure can be divided into three
      main steps. Firstly, a thresholding and a set of morphological operations were
      applied. Secondly, 3D connectivity analysis was defined to extract the objects
      forming part of the spinal canal. Finally, the centroid of each slice
      constituting the spinal canal object was computed. Furthermore, interpolation and
      extrapolation of data were performed, if required. The method was applied on two
      different groups, each one coming from different acquisition systems. A total of
      25 patients and 8704 images were used. An experienced radiologist evaluated the
      method qualitatively supporting the utility of it, as all extracted points fell
      into the spinal canal. Therefore, our method was able to reduce the workload and
      detect spinal canal objectively. We expect to carry out a quantitative evaluation
      in our future research. The qualitative outcome of this work suggests promising
      results. 

PMID- 25571244
TI  - Fully automatic spinal canal segmentation for radiation therapy using a gradient
      vector flow-based method on computed tomography images: A preliminary study.
AB  - Nowadays, radiotherapy is one of the key techniques for localized cancer
      treatment. Accurate identification of target volume (TV) and organs at risk (OAR)
      is a crucial step to therapy success. Spinal cord is one of the most
      radiosensitive OAR and its localization tends to be an observer-dependent and
      time-consuming task. Hence, numerous studies have aimed to carry out the
      contouring automatically. In CT images, there is a lack of contrast between soft
      tissues, making more challenge the delineation. That is the reason why the
      majority of researches have focused on spinal canal segmentation rather than
      spinal cord. In this work, we propose a fully automated method for spinal canal
      segmentation using a Gradient Vector Flow-based (GVF) algorithm. An experienced
      radiologist performed the manual segmentation, generating the ground truth. The
      method was evaluated on three different patients using the Dice coefficient,
      obtaining the following results: 79.50%, 83.77%, and 81.88%, respectively.
      Outcome reveals that more research has to be performed to improve the accuracy of
      the method. 

PMID- 25571245
TI  - Segmentation and reconstruction of cerebral vessels from 3D rotational
      angiography for AVM embolization planning.
AB  - Diagnosis and computer-guided therapy of cerebral Arterio-Venous Malformations
      (AVM) require an accurate understanding of the cerebral vascular network both
      from structural and biomechanical point of view. We propose to obtain such
      information by analyzing three Dimensional Rotational Angiography (3DRA) images.
      In this paper, we describe a two-step process allowing 1) the 3D automatic
      segmentation of cerebral vessels from 3DRA images using a region-growing based
      algorithm and 2) the reconstruction of the segmented vessels using the 3D
      constrained Delaunay Triangulation method. The proposed algorithm was
      successfully applied to reconstruct cerebral blood vessels from ten datasets of
      3DRA images. This software allows the neuroradiologist to separately analyze
      cerebral vessels for pre-operative interventions planning and therapeutic
      decision making. 

PMID- 25571246
TI  - Segmentation of densely populated cell nuclei from confocal image stacks using 3D
      non-parametric shape priors.
AB  - An approach to jointly estimate 3D shapes and poses of stained nuclei from
      confocal microscopy images, using statistical prior information, is presented.
      Extracting nuclei boundaries from our experimental images of cell migration is
      challenging due to clustered nuclei and variations in their shapes. This issue is
      formulated as a maximum a posteriori estimation problem. By incorporating
      statistical prior models of 3D nuclei shapes into level set functions, the active
      contour evolutions applied on the images is constrained. A 3D alignment algorithm
      is developed to build the training databases and to match contours obtained from
      the images to them. To address the issue of aligning the model over multiple
      clustered nuclei, a watershed-like technique is used to detect and separate
      clustered regions prior to active contour evolution. Our method is tested on
      confocal images of endothelial cells in microfluidic devices, compared with
      existing approaches. 

PMID- 25571247
TI  - Semi-automatic Fisher-Tippett guided active contour for lumbar multifidus muscle
      segmentation.
AB  - Rehabilitative Ultrasound Imaging or diagnostic ultrasound is used to measure
      geometric properties of the lumbar multifidus muscle to infer muscle strength or
      degeneration for back pain therapy. For this purpose, a novel semi-automatic
      approach (FTS: Fisher-Tippett Segmentation) based upon the Decoupled Active
      Contour is proposed to reliably and quickly segment the lumbar multifidus muscle
      in diagnostic ultrasound. To overcome speckle or hardly visible region boundaries
      in ultrasound images, we first propose a novel external energy functional to
      explicitly consider the underlying Fisher-Tippett distribution of ultrasound
      data. We then introduce a user-guided Hidden Markov Model trellis formation for
      improved segmentation of weakly-defined regions. Extensive experiments have shown
      that our approach not only improves the segmentation performance when compared to
      existing methods, but also does not rely on sub-specialized knowledge for
      segmentation. 

PMID- 25571248
TI  - Automated consensus contour building for prostate MRI.
AB  - Inter-observer variability is the lack of agreement among clinicians in
      contouring a given organ or tumour in a medical image. The variability in medical
      image contouring is a source of uncertainty in radiation treatment planning.
      Consensus contour of a given case, which was proposed to reduce the variability,
      is generated by combining the manually generated contours of several clinicians.
      However, having access to several clinicians (e.g., radiation oncologists) to
      generate a consensus contour for one patient is costly. This paper presents an
      algorithm that automatically generates a consensus contour for a given case using
      the atlases of different clinicians. The algorithm was applied to prostate MR
      images of 15 patients manually contoured by 5 clinicians. The automatic consensus
      contours were compared to manual consensus contours where a median Dice
      similarity coefficient (DSC) of 88% was achieved. 

PMID- 25571250
TI  - A curvelet-based morphological segmentation of abdominal CT images.
AB  - This paper presents a segmentation methodology of abdominal axial CT images. The
      aim of the study is to determine the location of mesenteric area from the axial
      images so the organs enclosed within can be localized precisely for diagnostic
      purposes. The challenge confronted here is that there is no a certain
      deterministic shape of abdominal organs. The methodology implemented here
      utilizes a curvelets stage followed by morphological image processing to achieve
      a contour emphasized segmentation from the gestalts of surrounding organs. This
      paper gives a detailed analysis of approach taken with the problems faced and a
      brief comparison wrt to other wavelet approaches. 

PMID- 25571249
TI  - Automatic kidney segmentation in CT images based on multi-atlas image
      registration.
AB  - Kidney segmentation is an important step for computer-aided diagnosis or
      treatment in urology. In this paper, we present an automatic method based on
      multi-atlas image registration for kidney segmentation. The method mainly relies
      on a two-step framework to obtain coarse-to-fine segmentation results. In the
      first step, down-sampled patient image is registered with a set of low-resolution
      atlas images. A coarse kidney segmentation result is generated to locate the left
      and right kidneys. In the second step, the left and right kidneys are cropped
      from original images and aligned with another set of high-resolution atlas images
      to obtain the final results respectively. Segmentation results from 14 CT
      angiographic (CTA) images show that our proposed method can segment the kidneys
      with a high accuracy. The average Dice similarity coefficient and surface-to
      surface distance between segmentation results and reference standard are 0.952
      and 0.913mm. Furthermore, the kidney segmentation in CT urography (CTU) and CTA
      images of 12 patients were performed to show the feasibility of our method in CTU
      images. 

PMID- 25571251
TI  - Efficient epidermis segmentation for whole slide skin histopathological images.
AB  - In order to develop a computer-aided diagnosis system for histopathological skin
      cancer diagnosis, segmentation of the epidermis area is the very first and
      crucial step. An improved computer-aided epidermis segmentation technique for the
      whole slide skin histopathological image is proposed in this paper. The proposed
      technique first obtains an initial segmentation result with the help of global
      thresholding and shape analysis. A template matching method, with adaptive
      template intensity value, is then applied. Finally, a threshold is calculated
      based on the probability density function of the processed image after template
      matching. The threshold is then used to obtain the final segmentation result.
      Experimental results show that the proposed technique overcomes the limitation of
      the existing technique and provides a superior performance with sensitivity at
      97.99%, and precision at 96.00%. 

PMID- 25571252
TI  - Multi-modal image registration using structural features.
AB  - Multi-modal image registration has been a challenging task in medical images
      because of the complex intensity relationship between images to be aligned.
      Registration methods often rely on the statistical intensity relationship between
      the images which suffers from problems such as statistical insufficiency. The
      proposed registration method works based on extracting structural features by
      utilizing the complex phase and gradient-based information. By employing
      structural relationships between different modalities instead of complex
      similarity measures, the multi-modal registration problem is converted into a
      mono-modal one. Therefore, conventional mono-modal similarity measures can be
      utilized to evaluate the registration results. This new registration paradigm has
      been tested on magnetic resonance (MR) brain images of different modes. The
      method has been evaluated based on target registration error (TRE) to determine
      alignment accuracy. Quantitative results demonstrate that the proposed method is
      capable of achieving comparable registration accuracy compared to the
      conventional mutual information. 

PMID- 25571253
TI  - A novel tamper detection-recovery and watermarking system for medical image
      authentication and EPR hiding.
AB  - Recently, the literature has witnessed an increasing interest in the study of
      medical image watermarking and recovery techniques. In this article, a novel
      image tamper localization and recovery technique for medical image authentication
      is proposed. The sparse coding of the Electronic Patient Record (EPR) and the
      reshaped region of Interest (ROI) is embedded in the transform domain of the
      Region of Non-Interest (RONI). The first part of the sparse coded watermark is
      use for saving the patient information along with the image, whereas the second
      part is used for authentication purpose. When the watermarked image is tampered
      during transmission between hospitals and medical clinics, the embedded sparse
      coded ROI can be extracted to recover the tampered image. The experimental
      results demonstrate the efficiency of the proposed technique in term of tamper
      correction capability, robustness to attacks, and imperceptibility. 

PMID- 25571254
TI  - Estimation of brain internal structures by deforming brain atlas using finite
      element method.
AB  - This paper presents a method for estimating the internal structures of a patient
      brain by deforming a standard brain atlas. Conventional deformation methods need
      several landmarks from the brain surface contour to fit the atlas to the patient
      brain shape. However, since the number and shapes of small sulci on the brain
      surface are different from each other, the determination of the accurate
      correspondence between small sulcus is difficult for experienced neurosurgeons.
      Moreover, the relationship between the surface shape and internal structure of
      the brain is unclear. Therefore, even if the deformed atlas is fitted to the
      patient brain shape exactly, the use of the deformed atlas does not always
      guarantee the reliable estimation of the internal structure of the patient brain.
      To solve these problems, we propose a new method for estimate the internal
      structure of a patient brain by the finite element method (FEM). In the
      deformation, our method select the landmarks from the contours of both the brain
      surface and the detectable internal structures from MR images. 

PMID- 25571255
TI  - A hybrid method for non-rigid registration of intra-operative ultrasound images
      with pre-operative MR images.
AB  - In recent years intra-operative ultrasound images have been used for many
      procedures in neurosurgery. The registration of intra-operative ultrasound images
      with preoperative magnetic resonance images is still a challenging problem. In
      this study a new hybrid method based on residual complexity is proposed for this
      problem. A new two stages method based on the matching echogenic structures such
      as sulci is achieved by optimizing the residual complexity (RC) value with
      quantized coefficients between the ultrasound image and the probabilistic map of
      MR image. The proposed method is a compromise between feature-based and intensity
      based approaches. The evaluation is performed on both a brain phantom and patient
      data set. The results of the phantom data set confirmed that the proposed method
      outperforms the accuracy of conventional RC by 39%. Also the mean of fiducial
      registration errors reached to 1.45, 1.94 mm when the method was applied on
      phantom and clinical data set, respectively. This hybrid method based on RC
      enables non-rigid multimodal image registration in a computational time
      compatible with clinical use as well as being accurate. 

PMID- 25571256
TI  - A shape based rotation invariant method for ultrasound-MR image registration: A
      phantom study.
AB  - In this work, a new shape based method to improve the accuracy of Brain
      Ultrasound-MRI image registration is proposed. The method is based on modified
      Shape Context (SC) descriptor in combination with CPD algorithm. An extensive
      experiment was carried out to evaluate the robustness of this method against
      different initialization conditions. As the results prove, the overall
      performance of the proposed algorithm outperforms both SC and CPD methods. In
      order to have control over the registration procedure, we simulated the
      deformations, missing points and outliers according to our Phantom MRI images. 

PMID- 25571257
TI  - Virtual navigator automatic registration technology in abdominal application.
AB  - Real-time Ultrasound (US) image fusion with a pre-acquired second imaging dataset
      - Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and/or CT/PET - has
      become widely used in recent years for both diagnosis and image-guided
      interventional procedures. Liver and kidneys are the main focused anatomical
      districts, related to abdominal application. There are still nowadays some
      drawbacks, regarding the adoption of the fusion imaging technique in everyday
      practice especially regarding its ease of use and the time needed in order to
      obtain a precise real-time fusion between US and the second imaging modality. The
      present work is a preliminary study on the feasibility and practical use of an
      Automatic registration algorithm for CT-US real-time fusion imaging. Data
      obtained by tests performed on a Doppler phantom, for the assessment of the
      precision of the registration procedure and in-vivo Automatic registration tests,
      are presented. 

PMID- 25571258
TI  - Automatic registration of pre- and intraoperative data for long bones in
      minimally invasive surgery.
AB  - The Minimally Invasive Procedures (MIP) in orthopedics have grown rapidly
      worldwide, as clinical results indicate that patients who undergo MIP typically
      experience minimized blood loss, smaller incision and shorter hospital stays. For
      most MIP, a preoperative 3D model of the patient anatomy is usually generated in
      order to plan the surgery. The challenge in MIP consists in finding the
      correspondence between the preoperative model and the actual position of the
      patient in the operating room, also known as image-to-patient registration. This
      paper proposes a real-time solution based on ultrasound (US) images: the patient
      anatomy is scanned by an US probe. Then, the segmentation and the extraction of
      bone contours from US images result in a 3D point cloud. The Poisson surface
      reconstruction method provides a 3D surface from 2D US data which will be
      registered with the preoperative model (CT volume) using the principal axes of
      inertia and the Iterative Closest Point robust (ICPr) algorithm. We present
      quantitative and qualitative results on both phantom and clinical data and show a
      mean registration accuracy of 0.66 mm for clinical radius scan. The promising
      registration results show the possible use of the proposed registration algorithm
      in clinical procedures. 

PMID- 25571259
TI  - Fusion of structural and functional cardiac magnetic resonance imaging data for
      studying ventricular fibrillation.
AB  - Magnetic Resonance Imaging (MRI) techniques such as Current Density Imaging (CDI)
      and Diffusion Tensor Imaging (DTI) provide a complementing set of imaging data
      that can describe both the functional and structural states of biological
      tissues. This paper presents a Joint Independent Component Analysis (jICA) based
      fusion approach which can be utilized to fuse CDI and DTI data to quantify the
      differences between two cardiac states: Ventricular Fibrillation (VF) and
      Asystolic/Normal (AS/NM). Such an approach could lead to a better insight on the
      mechanism of VF. Fusing CDI and DTI data from 8 data sets from 6 beating porcine
      hearts, in effect, detects the differences between two cardiac states,
      qualitatively and quantitatively. This initial study demonstrates the
      applicability of MRI-based imaging techniques and jICA-based fusion approach in
      studying cardiac arrhythmias. 

PMID- 25571260
TI  - 3D thermal medical image visualization tool: Integration between MRI and
      thermographic images.
AB  - Three-dimensional medical image reconstruction using different images modalities
      require registration techniques that are, in general, based on the stacking of 2D
      MRI/CT images slices. In this way, the integration of two different imaging
      modalities: anatomical (MRI/CT) and physiological information (infrared image),
      to generate a 3D thermal model, is a new methodology still under development.
      This paper presents a 3D THERMO interface that provides flexibility for the 3D
      visualization: it incorporates the DICOM parameters; different color scale
      palettes at the final 3D model; 3D visualization at different planes of sections;
      and a filtering option that provides better image visualization. To summarize,
      the 3D thermographc medical image visualization provides a realistic and precise
      medical tool. The merging of two different imaging modalities allows better
      quality and more fidelity, especially for medical applications in which the
      temperature changes are clinically significant. 

PMID- 25571261
TI  - Development of a specific tracer for metabolic imaging of alveolar
      echinococcosis: A preclinical study.
AB  - Positron emission tomography (PET)-computed tomography (CT) using [18F]
      fluorodeoxyglucose (FDG) (FDG-PET/CT) is a valuable method for initial staging
      and follow up of patients with alveolar echinococcosis (AE). However, the cells
      responsible for FDG uptake have not been clearly identified. The main goal of our
      study was to evaluate the uptake of PET tracers by the cells involved in the host
      parasite reaction around AE lesions as the first step to develop a specific PET
      tracer that would allow direct assessment of parasite viability in AE. Candidate
      molecules ([18F]-fluorotyrosine (FET), [18F]-fluorothymidine (FLT), and [18F]
      fluorometylcholine (FMC), were compared to FDG by in vitro studies on human
      leukocytes and parasite vesicles. Our results confirmed that FDG was mainly
      consumed by immune cells and showed that FLT was the best candidate tracer for
      parasite metabolism. Indeed, parasite cells exhibited high uptake of FLT. We also
      performed PET/CT scans in mice infected intraperitoneally with E. multilocularis
      metacestodes. PET images showed no FDG or FLT uptake in parasitic lesions. This
      preliminary study assessed the metabolic activity of human leukocytes and AE
      cells using radiolabeling. Future studies could develop a specific PET tracer for
      AE lesions to improve lesion detection and echinococcosis treatment in patients.
      Our results demonstrated that a new animal model is needed for preclinical PET
      imaging to better mimic human hepatic and/or periparasitic metabolism. 

PMID- 25571262
TI  - Measurement of motion detection of wireless capsule endoscope inside large
      intestine.
AB  - Wireless Capsule Endoscope (WCE) provides a noninvasive way to inspect the entire
      Gastrointestinal (GI) tract, including large intestine, where intestinal diseases
      most likely occur. As a critical component of capsule endoscopic examination,
      physicians need to know the precise position of the endoscopic capsule in order
      to identify the position of detected intestinal diseases. Knowing how the capsule
      moves inside the large intestine would greatly complement the existing wireless
      localization systems by providing the motion information. Since the most recently
      released WCE can take up to 6 frames per second, it's possible to estimate the
      movement of the capsule by processing the successive image sequence. In this
      paper, a computer vision based approach without utilizing any external device is
      proposed to estimate the motion of WCE inside the large intestine. The proposed
      approach estimate the displacement and rotation of the capsule by calculating
      entropy and mutual information between frames using Fibonacci method. The
      obtained results of this approach show its stability and better performance over
      other existing approaches of motion measurements. Meanwhile, findings of this
      paper lay a foundation for motion pattern of WCEs inside the large intestine,
      which will benefit other medical applications. 

PMID- 25571264
TI  - Support vector regression based multivariate lesion-symptom mapping.
AB  - A novel multivariate lesion-symptom mapping (LSM) methodology was developed in
      this study. Lesion analysis is a classic model for studying brain functions.
      Using lesion data, focal brain-behavior associations have been widely assessed
      using the massive voxel-based lesion symptom mapping (VLSM) method. Assessing
      each voxel independently, VLSM suffers from low sensitivity after correcting for
      the enormous number of comparisons. It is also incapable for assessing a
      spatially distributed association pattern though the brain-behavior associations
      generally involve a collection of functionally related voxels. To solve these two
      outstanding problems, we carried out the first multivariate lesion symptom
      mapping (MLSM) in this study using support vector regression (SVR). In the so
      dubbed SVR-LSM, the symptom relation to the entire lesion map rather than each
      isolated voxel is modeled using a non-linear function, so the inter-voxel
      correlations are intrinsically considered, resulting in a potentially more
      sensitive way to examine lesion-symptom relationships. Evaluations using
      synthetic data and real data showed that SVR-LSM gained a much better performance
      (in terms of sensitivity and specificity) for detecting brain-behavior relations
      than VLSM. While the method was designed for lesion analysis, extending it to
      neuroimaging data will be straightforward. 

PMID- 25571265
TI  - Anisotropic analysis of trabecular architecture in human femur bone radiographs
      using quaternion wavelet transforms.
AB  - In this work, anisotropy of compressive and tensile strength regions of femur
      trabecular bone are analysed using quaternion wavelet transforms. The normal and
      abnormal femur trabecular bone radiographic images are considered for this study.
      The sub-anatomic regions, which include compressive and tensile regions, are
      delineated using pre-processing procedures. These delineated regions are
      subjected to quaternion wavelet transforms and statistical parameters are derived
      from the transformed images. These parameters are correlated with apparent
      porosity, which is derived from the strength regions. Further, anisotropy is also
      calculated from the transformed images and is analyzed. Results show that the
      anisotropy values derived from second and third phase components of quaternion
      wavelet transform are found to be distinct for normal and abnormal samples with
      high statistical significance for both compressive and tensile regions. These
      investigations demonstrate that architectural anisotropy derived from QWT
      analysis is able to differentiate normal and abnormal samples. 

PMID- 25571263
TI  - Lateralization of temporal lobe epilepsy by imaging-based response-driven
      multinomial multivariate models.
AB  - We have developed response-driven multinomial models, based on multivariate
      imaging features, to lateralize the epileptogenicity in temporal lobe epilepsy
      (TLE) patients. To this end, volumetrics and statistical quantities of FLAIR
      intensity and normalized ictal-interictal SPECT intensity on left and right
      hippocampi were extracted from preoperative images of forty-five retrospective
      TLE patients with surgical outcome of Engel class l. Using multinomial logistic
      function regression, the parameters of various univariate and multivariate models
      were estimated. Among univariate response models, the response model with SPECT
      attributes and response model with mean FLAIR attributes achieved the lowest fit
      deviance (65.1+/-0.2 and 65.5+/-0.3, respectively). They resulted in the highest
      probability of detection (0.82) and lowest probability of false alarm (0.02) for
      the epileptogenic side. The multivariate response model with incorporating all
      volumetrics, mean and standard deviation FLAIR, and SPECT attributes achieved a
      significantly lower fit deviance than other response models (11.9+/-0.1, p <;
      0.001). It reached probability of detection of 1 with no false alarms. We were
      able to correctly lateralize the fifteen TLE patients who had undergone phase II
      intracranial monitoring. Therefore, the phase II intracranial monitoring might
      have been avoided for this set of patients. Based on this lateralization response
      model, the side of epileptogenicity was also detected for all thirty patients who
      had preceded to resection with only phase I of EEG monitoring. In conclusion, the
      proposed multinomial multivariate response-driven model for lateralization of
      epileptogenicity in TLE patients can help in decision-making prior to surgical
      resection and may reduce the need for implantation of intracranial monitoring
      electrodes. 

PMID- 25571267
TI  - Local sparse component analysis for blind source separation: an application to
      resting state FMRI.
AB  - We propose a new Blind Source Separation technique for whole-brain activity
      estimation that best profits from FMRI's intrinsic spatial sparsity. The Local
      Sparse Component Analysis (LSCA) combines wavelet analysis, group-separable
      regularizers, contiguity-constrained clusterization and principal components
      analysis (PCA) into a unique spatial sparse representation of FMRI images towards
      efficient dimensionality reduction without sacrificing physiological
      characteristics by avoiding artificial stochastic model constraints. The LSCA
      outperforms classical PCA source reconstruction for artificial data sets over
      many noise levels. A real FMRI data illustration reveals resting-state activities
      in regions hard to observe, such as thalamus and basal ganglia, because of their
      small spatial scale. 

PMID- 25571266
TI  - BOLD effect on calf muscle groups in elderly females with different bone mineral
      density.
AB  - This study examined the BOLD effect on calf muscles in elderly subjects with
      different bone mineral density. The purpose was to investigate the oxygenation
      characteristics in different calf muscle groups for the elderly females and
      compare the muscle oxygenation among groups with different bone mineral density.
      Temporary vascular occlusion was induced with air-cuff compression of the thigh
      and BOLD-MRI data curve was fitted to derive quantitative parameters. Three
      muscle groups, gastrocnemius muscle (lateral head), soleus muscle, and tibialis
      anterior muscle, were investigated individually. Quantitative CT measurement was
      conducted on each subject, based on which subjects were classified into normal,
      osteopenia, and osteoporosis groups. The BOLD signal in soleus muscle showed the
      lowest minimum ischemic value during ischemia and the steepest slope during
      hyperemia. As soleus muscle is mainly composed by slow-twitch oxidative muscle
      fibers, current results may be due to a higher vascular bed density and better
      endothelial function in such muscle. By t-test, the half-life of the BOLD signal
      decay during ischemia in both gastrocnemius and soleus muscles was significantly
      prolonged in osteoporosis group, indicating a degenerated muscular oxygen
      metabolic capacity in osteoporotic patients. 

PMID- 25571268
TI  - A video-based speed estimation technique for localizing the wireless capsule
      endoscope inside gastrointestinal tract.
AB  - Wireless Capsule Endoscopy (WCE) is progressively emerging as one of the most
      popular non-invasive imaging tools for gastrointestinal (GI) tract inspection. As
      a critical component of capsule endoscopic examination, physicians need to know
      the precise position of the endoscopic capsule in order to identify the position
      of intestinal disease. For the WCE, the position of the capsule is defined as the
      linear distance it is away from certain fixed anatomical landmarks. In order to
      measure the distance the capsule has traveled, a precise knowledge of how fast
      the capsule moves is urgently needed. In this paper, we present a novel computer
      vision based speed estimation technique that is able to extract the speed of the
      endoscopic capsule by analyzing the displacements between consecutive frames. The
      proposed approach is validated using a virtual testbed as well as the real
      endoscopic images. Results show that the proposed method is able to precisely
      estimate the speed of the endoscopic capsule with 93% accuracy on average, which
      enhances the localization accuracy of the WCE to less than 2.49 cm. 

PMID- 25571269
TI  - Characterization and quantification of curvature using independent coordinates
      method in the human left ventricle by magnetic resonance imaging to identify the
      morphology subtype of hypertrophy cardiomyopathy.
AB  - The patterns of ventricular hypertrophy are critical determinants of blood flow
      and function, but are variable. Therefore, it is clinically relevant to assess
      the hypertrophic shape patterns to better characterize and identify the
      morphological subtypes. We proposed and developed an independent coordinates
      method (ICM) to quantify the regional shape of the left ventricle in terms of
      curvature. 19 normal subjects and 5 HCM (hypertrophic cardiomyopathy) patients
      with different morphological subtype (i.e., septal hypertrophy, mid-ventricular
      hypertrophy, reverse curvature septum hypertrophy and sigmoid septum hypertrophy)
      were recruited and underwent magnetic resonance scans. The curvature along the
      endocardial and epicardial surface was computed using ICM method and was compared
      in HCM patients against normal subjects. The results showed that curvature plots
      are variable in different morphological subtype. The curvature pattern
      demonstrated the utilities in delineating different subtype. In conclusion, ICM
      method to quantify regional curvature of the left ventricle from magnetic
      resonance imaging are feasible in normal subjects and those with hypertrophy
      cardiomyopathy, which may serve as a novel approach to depict local shape of the
      left ventricle and to assess the morphological subtype in clinical practice.

PMID- 25571270
TI  - Finite element analysis of stent implantation in a three-dimensional
      reconstructed arterial segment.
AB  - Endovascular stent deployment is a mechanical procedure used to rehabilitate a
      diseased arterial segment by restoring blood flow in occluded regions. The
      success or failure of the stent implantation depends on the stent device and the
      deployment technique. The optimal stent deployment can be predicted by
      investigating the factors that influence this minimally invasive procedure. In
      this study, we propose a methodology which evaluates the alterations in the
      arterial environment caused by stent deployment. A finite element model of a
      reconstructed right coronary artery with a stenosis was created based on
      anatomical information provided by intravascular ultrasound and angiography. The
      model was used to consider placement and performance after intervention with a
      commercially available Leader Plus stent. The performance of the stent, within
      this patient-specific arterial segment is presented, as well as the induced
      arterial deformation and straightening. The arterial stress distribution is
      analyzed with respect to possible regions of arterial injury. Our approach can be
      used to optimize stent deployment and to provide cardiologists with a valuable
      tool to visually select the position and deploy stents in patient-specific
      reconstructed arterial segments, thereby enabling new methods for optimal
      cardiovascular stent positioning. 

PMID- 25571272
TI  - A phantom with pulsating artificial vessels for non-invasive fetal pulse
      oximetry.
AB  - Arterial oxygen saturation of the fetus is an important parameter for monitoring
      its physical condition. During labor and delivery the transabdominal non-invasive
      fetal pulse oximetry could minimize the risk for mother and fetus, compared to
      other existing invasive examination methods. In this contribution, we developed a
      physical-like phantom to investigate new sensor circuits and algorithms of a non
      invasive diagnostic method for fetal pulse oximetry. Hence, the developed
      artificial vascular system consists of two independent tube systems representing
      the maternal and fetal vessel system. The arterial blood pressure is reproduced
      with a pre-pressure and an artificial vascular system. Each pulse wave can be
      reproduced, by digital control of a proportional valve, adjustable viscoelastic
      elements, and resistances. The measurements are performed by pressure
      transducers, optical sensor units, and a coplanar capacitive sensor. Transmission
      and reflection measurements have shown that the fetal and maternal pulse waves
      can be reproduced qualitatively. The measured light represents the transabdominal
      modulated signal on an abdomen of a pregnant woman. 

PMID- 25571271
TI  - Estimation of ultrasound strain indices in carotid plaque and correlation to
      cognitive dysfunction.
AB  - Carotid plaque prone to release emboli may be predicted by increased strain
      variations within plaque due to arterial pulsation over a cardiac cycle. Non
      invasive ultrasound strain imaging may therefore be a viable surrogate to
      determine the risk of embolic stroke and possible cognitive impairment.
      Ultrasound strain imaging was performed on 24 human subjects with significant
      plaque, who also underwent standardized cognitive assessment (Repeatable Battery
      for the Assessment of Neuropsychological Status (RBANS)) prior to a carotid
      endarterectomy (CEA) procedure. Radiofrequency signals were acquired using a
      Siemens Antares with a VFX 13-5 linear array transducer. Plaque regions were
      segmented by a radiologist at end-diastole using the Medical Imaging Interaction
      Toolkit. A hierarchical block-matching motion tracking algorithm was utilized to
      estimate the cumulated axial, lateral, and shear strains within the imaging
      plane. The maximum strain indices of the plaque, defined as mean accumulated
      strain over a small region of interest in the plaque with large deformations,
      were obtained. All the strain indices were then correlated with RBANS Total
      score. Overall cognitive performance was negatively associated with maximum axial
      and lateral strains respectively. The results demonstrate a direct relationship
      between the maximum axial and lateral strain indices in carotid plaque and
      cognitive impairment. 

PMID- 25571273
TI  - Variation of radial pulse wave contour influenced by contact pressure.
AB  - In this paper, the radial pulse waveforms of the same subjects under various
      contact pressures were measured. Then, the feature points of the pulse wave
      contours were extracted and the physical parameters were calculated corresponding
      to different contact pressures. The various trends of parameters, including
      peripheral augmentation index, peripheral subendocardial viability ratio, and
      peripheral resistance, influenced by contact pressures were analyzed. By
      comparing the variation trend between different subject groups, it is notable
      that there exists a significant difference between the parameters of young
      healthy people and elder patients (P<0.01). Moreover, the peripheral augmentation
      index, SEVR and the peripheral resistance descend with increased contact
      pressure, because of the variation of pulse wave contour.

PMID- 25571274
TI  - Automatic quality classification of entire electrocardiographic recordings
      obtained with a novel patch type recorder.
AB  - Recently, new patch type electrocardiogram (ECG) recorders have reached the
      market. These new devices possess a number of advantages compared to the
      traditional Holter recorders. This forms the basis of questions related to
      benefits and drawbacks of different ambulatory ECG recording techniques. One of
      the important questions is the ability to obtain high clinical quality of the
      recordings during the entire monitoring period. It is thus desirable to be able
      to obtain an automatic estimate of the global quality of entire ECG recordings.
      The purpose of this pilot study is therefore to design an algorithm for automatic
      classification of entire ECG recordings into the groups "noisy" and "clean"
      recordings. This novel algorithm is based on three features and a simple Bayes
      classifier. The algorithm was tested on 40 ECG recordings in a five-fold cross
      validation scheme and it obtained an average accuracy of 90% on the test data. 

PMID- 25571275
TI  - Assessing the hemodynamic influence between multiple lesions in a realistic right
      coronary artery segment: A computational study.
AB  - Coronary artery disease is the primary cause of morbidity and mortality
      worldwide. Therefore, detailed assessment of lesions in the coronary vasculature
      is critical in current clinical practice. Fractional flow reserve (FFR) has been
      proven as an efficient method for assessing the hemodynamic severity of a
      coronary stenosis. However, functional assessment of a coronary segment with
      multiple stenoses (>= 2) remains complex for guiding the strategy of percutaneous
      coronary intervention due to the hemodynamic interplay between adjacent stenoses.
      In this work, we created four 3-dimensional (3D) arterial models that derive from
      a healthy patient-specific right coronary artery segment. The initial healthy
      model was reconstructed using fusion of intravascular ultrasound (IVUS) and
      biplane angiographic patient data. The healthy 3D model presented a measured FFR
      value of 0.96 (pressure-wire) and a simulated FFR value of 0.98. We then created
      diseased models with two artificial sequential stenoses of 90% lumen area
      reduction or with the proximal and distal stenosis separately. We calculated the
      FFR value for each case: 0.65 for the case with the two stenoses, 0.73 for the
      case with the distal stenosis and 0.90 for the case with the proximal stenosis.
      This leads to the conclusion that although both stenoses had the same degree of
      lumen area stenosis, there was a large difference in hemodynamic severity,
      thereby indicating that angiographic lumen assessment by itself is often not
      adequate for accurate assessment of coronary lesions.

PMID- 25571276
TI  - An augmented reality framework for optimization of computer assisted navigation
      in endovascular surgery.
AB  - Endovascular surgery is performed by placing a catheter through blood vessels.
      Due to the fragility of arteries and the difficulty in controlling a long elastic
      wire to reach the target region, training plays an extremely important role in
      helping a surgeon acquire the required complex skills. Virtual reality simulators
      and augmented reality systems have proven to be effective in minimally invasive
      surgical training. These systems, however, often employ pre-captured or computer
      generated medical images. We have developed an augmented reality system for
      ultrasound-guided endovascular surgical training, where real ultrasound images
      captured during the procedure are registered with a pre-scanned phantom model to
      give the operator a realistic experience. Our goal is to extend the planning and
      training environment to deliver a system for computer assisted remote
      endovascular surgery where the navigation of a catheter can be controlled through
      a robotic device based on the guidance provided by an endovascular surgeon. 

PMID- 25571277
TI  - Numerical model of total artificial heart hemodynamics and the effect of its size
      on stress accumulation.
AB  - The total artificial heart (TAH) is a bi-ventricular mechanical circulatory
      support device that replaces the heart in patients with end-stage congestive
      heart failure. The device acts as blood pump via pneumatic activation of
      diaphragms altering the volume of the ventricular chambers. Flow in and out of
      the ventricles is controlled by mechanical heart valves. The aim of this study is
      to evaluate the flow regime in the TAH and to estimate the thrombogenic potential
      during systole. Toward that goal, three numerical models of TAHs of differing
      sizes, that include the deforming diaphragm and the blood flow from the left
      chamber to the aorta, are introduced. A multiphase model with injection of
      platelet particles is employed to calculate their trajectories. The shear stress
      accumulation in the three models are calculated along the platelets trajectories
      and their probability density functions, which represent the 'thrombogenic
      footprint' of the device are compared. The calculated flow regime successfully
      captures the mitral regurgitation and the flows that open and close the aortic
      valve during systole. Physiological velocity magnitudes are found in all three
      models, with higher velocities and increased stress accumulation predicted for
      smaller devices. 

PMID- 25571278
TI  - Mechanical heart valve cavitation in patients with bileaflet valves.
AB  - Today, the quality of mechanical heart valves is quite high, and implantation has
      become a routine clinical procedure with a low operative mortality (< 5%).
      However, patients still face the risks of blood cell damage, thromboembolic
      events, and material failure of the prosthetic device. One mechanism found to be
      a possible contributor to these adverse effects is cavitation. In vitro,
      cavitation has been directly demonstrated by visualization and indirectly in vivo
      by registering of high frequency pressure fluctuations (HFPF). Tilting disc
      valves are thought of having higher cavitation potential than bileaflet valves
      due to higher closing velocities. However, the thromboembolic potential seems to
      be the same. Further studies are therefore needed to investigate the cavitation
      potential of bileaflet valves in vivo. The post processing of HFPF have shown
      difficulties when applied on bileaflet vavles due to asynchronous closure of the
      two leaflets. The aim of this study was therefore to isolate the pressure
      signature from each leaflet closure and perform cavitation analyses on each
      component. Six patients were included in the study (St. Jude Medical (n=3) and
      CarboMedics (n=3); all aortic bileaflet mechanical heart valves). HFPFs were
      recorded intraoperatively through a hydrophone at the aortic root. The pressure
      signature relating to the first and second leaflet closure was isolated and
      cavitation parameters were calculated (RMS after 50 kHz highpass filtering and
      signal energy). Data were averaged over 30 heart cycles. For all patients both
      the RMS value and signal energy of the second leaflet closure were higher than
      for the first leaflet closure. This indicates that the second leaflet closure is
      most prone to cause cavitation. Therefore, quantifying cavitation based on the
      HFPF related to the second leaflet closure may suggest that the cavitation
      potential for bileaflet valves in vivo may be higher than previous studies have
      suggested.

PMID- 25571279
TI  - Pulsatile operation of the BiVACOR TAH - Motor design, control and hemodynamics.
AB  - Although there is limited consensus about the strict requirement to deliver
      pulsatile perfusion to the human circulatory system, speed modulation of rotary
      blood pumps is an approach that may capture the benefits of both positive
      displacement and continuous flow blood pumps. In the current stage of development
      of the BiVACOR Total Artificial Heart emphasis is placed on providing pulsatile
      outflow from the pump. Multiple pulsatile speed profiles have been applied in
      preliminary in-vivo operation in order to assess the capability of the TAH to
      recreate a physiologic pulse. This paper provides an overview about recent
      research towards pulsatile BiVACOR operation with special emphasis on motor and
      control requirements and developments. 

PMID- 25571280
TI  - Inducing valvular regurgitation in mice via thermal ablation of cardiac valves.
AB  - This study presents early data in the development of a novel mouse model of heart
      failure utilizing thermal ablation on cardiac valves to induce valvular
      regurgitation. Thermal ablation of the valve was achieved through the application
      of radiofrequency (RF) electrical current. The objective was to apply enough
      energy to induce valve stiffening and retraction, which was hypothesized to
      produce valve insufficiency and blood regurgitation in vivo. Preliminary studies
      were performed to develop a workable energy delivery catheter that could be
      inserted through the carotid artery to the aortic valve. Catheter position
      between the aortic valve leaflets was verified by echocardiography. Valve
      function was evaluated before and after the thermal insult using Doppler
      measurements near the valve inflow and outflow, and early results demonstrate
      that the energy delivery catheter could successfully induce acute valve
      insufficiency. Further study is needed to refine the catheter to provide greater
      control over the degree of thermal damage and resulting changes in cardiac
      physiology. 

PMID- 25571281
TI  - A mock circulatory loop for designing and evaluating total artificial hearts.
AB  - A mock circulatory loop was constructed to facilitate total artificial heart
      development. The loop includes many novel features such as a pressure-regulated
      tank to simulate exercise conditions, controllable systemic and pulmonary
      vascular resistance to create left-right flow imbalances as seen in postural
      change and breathing, and a left atrial suction valve. Dual HeartMate II pumps
      and the BiVACOR(r) rotary total artificial heart were used to generate pressure
      and flow data characterizing the flow loop. 

PMID- 25571282
TI  - Dynamic blood flow and wall shear stress in pulmonary hypertensive disease.
AB  - This study provides new model of pulsatile flow in the pulmonary circulation in
      health and pulmonary hypertensive disease. Structural vascular remodeling typical
      of pulmonary hypertensive disease was implemented in the model by progressively
      altering the mechanical properties of the arterial geometry and progressively
      increasing the inlet pulse pressure (PP). The transmission of PP throughout the
      tree was shown to increase in advanced stages of disease, creating the potential
      for a 'vicious-cycle' of damage to vasculature. Wall shear stress (WSS) was shown
      to be highest in the terminal arteries of the model and increased significantly
      with disease. A further trend observed in WSS results was that high WSS values
      began to 'climb' the arterial tree towards the proximal vessels as disease
      progressed. This suggests a link between WSS and distal remodeling in pulmonary
      hypertensive disease, which initiates in the small muscular arteries and
      arterioles and spreads into larger arteries as the disease progresses. 

PMID- 25571283
TI  - Modeling of milk flow in mammary ducts in lactating human female breast.
AB  - A transient laminar Newtonian three-dimensional CFD simulation has been studied
      for milk flow in a phantom model of the 6-generations human lactating breast
      branching system. Milk is extracted by the cyclic pattern of suction from the
      alveoli through the duct and to the nipple. The real negative (suction) pressure
      data are applied as an outlet boundary condition in nipple. In this study, the
      commercial CFD code (Fluent Inc., 2004) is employed for the numerical solution of
      the milk flow. The milk intake flow rate from simulation is compared to the real
      clinical data from published paper. The results are in good agreement. It is
      believed that the methodology of the lactating human breast branching modeling
      proposed here can provide potential guidelines for further clinical and research
      application. 

PMID- 25571284
TI  - A MUm-resolution heterogeneous tissue model for the magnetic stimulation of
      multifascicular sciatic nerve.
AB  - Efficacy of magnetic stimulation of the central or peripheral nervous system
      depends on the spatial and temporal distribution of the induced electric field
      generated by the magnetic coil. Therefore, accurate estimation of the induced
      electric field is crucial to the design and optimization of magnetic coils,
      particularly as the coil dimensions are reduced. In this work, we developed a
      numerical model of a multifascicular sciatic nerve to study the effect of tissue
      heterogeneity on the induced electric field. Using a multi-resolution electric
      field solver, we can resolve feature sizes as small as 1MUm, allowing inclusion
      of the nerve membrane and the myelination layer. Preliminary results indicate
      that fascicle distribution and axons' proximity to each other significantly
      affect the magnitude and distribution of the induced electric field as compared
      to traditional homogeneous tissue models for field simulation. 

PMID- 25571285
TI  - A mathematical model of bipolar radiofrequency-induced thermofusion.
AB  - Bipolar radiofrequency-induced thermofusion has become a widely accepted method
      successfully used in open and particularly in minimally-invasive surgery for the
      sealing of blood vessels and tissue of up to several millimeters diameter.
      Despite its wide-spread application, the thermofusion process itself is not well
      understood on a quantitative and dynamic level, and manufacturers largely rely on
      trial-and-error methods to improve existing instruments. To predict the effect of
      alternative generator control strategies and to allow for a more systematic
      approach to improve thermofusion instruments, a mathematical model of the
      thermofusion process is developed. The system equations describe the spatial and
      temporal evolution of the tissue temperature due to Joule heating and heat
      transfer, and the loss of tissue water due to vaporization. The resulting effects
      on the tissue properties, most importantly the electrical resistivity, heat
      capacity and thermal conductivity, are considered as well. Experimental results
      indicate that the extent of the lateral thermal damage is directly affected by
      Joule heating of the lateral tissue. The experimental findings are supported by
      simulation results using the proposed mathematical model of thermofusion. 

PMID- 25571286
TI  - Mathematical analysis of mammary ducts in lactating human breast.
AB  - This work studies a simple model for milk transport through lactating human
      breast ducts, and describes mathematically the mass transfer from alveolar sacs
      through the mammary ducts to the nipple. In this model both the phenomena of
      diffusion in the sacs and conventional flow in ducts have been considered. The
      ensuing analysis reveals that there is an optimal range of bifurcation numbers
      leading to the easiest milk flow based on the minimum flow resistance. This model
      formulates certain difficult-to-measure values like diameter of the alveolar
      sacs, and the total length of the milk path as a function of easy-to-measure
      properties such as milk fluid properties and macroscopic measurements of the
      breast. Alveolar dimensions from breast tissues of six lactating women are
      measured and reported in this paper. The theoretically calculated alveoli
      diameters for optimum milk flow (as a function of bifurcation numbers) show
      excellent match with our biological data on alveolar dimensions. Also, the
      mathematical model indicates that for minimum milk flow resistance the glandular
      tissue must be within a short distance from the base of the nipple, an
      observation that matches well with the latest anatomical and physiological
      research. 

PMID- 25571287
TI  - Modeling prediction of a generalized habituation deficit in decompensated
      tinnitus sufferers.
AB  - The pathologic auditory sensation in decompensated tinnitus patients is
      accompanied by the inability to habituate even temporary to this sound. This
      disability might originate from simultaneous activation of brain areas for the
      appraisal of the stimulus valence as, e.g., the limbic system. This coactivation
      of limbic areas is likely to modulate the degree and persistence of selective
      attention assigned to the tinnitus stream, which in turn could also explain
      interindividual differences in tinnitus loudness perception. Preliminary studies
      demonstrate that the amount of allocated attention and the habituation deficit
      can be mapped to changes in auditory late evoked responses (ALRs). Utilizing a
      numerical model for the simulation of ALRs we were able to predict a general
      habituation behavior in two patient groups with different degrees of tinnitus
      severity. Evaluating the instantaneous phase of simulated and measured ALRs by
      its von Mises concentration parameter, we verify a habituation deficit relative
      to the degree of decompensation and thus provide additional support for our
      neurofunctional model of limbic influences on neural processing of sensory
      information. 

PMID- 25571288
TI  - In silico simulations of experimental protocols for cardiac modeling.
AB  - A mathematical model of the AP involves the sum of different transmembrane ionic
      currents and the balance of intracellular ionic concentrations. To each ionic
      current corresponds an equation involving several effects. There are a number of
      model parameters that must be identified using specific experimental protocols in
      which the effects are considered as independent. However, when the model
      complexity grows, the interaction between effects becomes increasingly important.
      Therefore, model parameters identified considering the different effects as
      independent might be misleading. In this work, a novel methodology consisting in
      performing in silico simulations of the experimental protocol and then comparing
      experimental and simulated outcomes is proposed for parameter model
      identification and validation. The potential of the methodology is demonstrated
      by validating voltage-dependent L-type calcium current (ICaL) inactivation in
      recently proposed human ventricular AP models with different formulations. Our
      results show large differences between ICaL inactivation as calculated from the
      model equation and ICaL inactivation from the in silico simulations due to the
      interaction between effects and/or to the experimental protocol. Our results
      suggest that, when proposing any new model formulation, consistency between such
      formulation and the corresponding experimental data that is aimed at being
      reproduced needs to be first verified considering all involved factors. 

PMID- 25571289
TI  - A pharmacokinetic model of lopinavir in combination with ritonavir in human.
AB  - Ritonavir-boosted lopinavir (LPV/r) has been recommended as an alternative
      regimen for HIV-naive patients who cannot tolerate nevirapine (NVP) and/or
      efavirenz (EFV). Although combinations of ritonavir and lopinavir have shown
      higher plasma concentration level of LPV in clinical settings, dosage adjustment
      is still required to maintain an adequate therapeutic efficacy and reduce side
      effects. A compartmental pharmacokinetic (PK) model of LPV/r was developed,
      including a mechanistic description of competitive inhibition. Systematic
      simulations were performed and predicted plasma drug concentration levels were
      compared with those from the literature. In particular, the simulated and
      experimental area under the curve (AUC) based on oral dosing were 76.10 MUMol/L,
      and 76.25 MUMol/L, respectively Results from the mathematical model support the
      hypothesis that the mechanism of LPV/r interaction is due to the competitive
      inhibition of CYP3A4 in the liver by ritonavir, resulting in an increasing LPV
      plasma concentration levels. The simulated plasma concentration-time courses were
      consistent with those from the literature with the goodness of fit (R(2)) of
      0.9025 (0.8269-0.9862 95%CI). 

PMID- 25571290
TI  - A pharmacokinetic drug-drug interaction model of simvastatin and clarithromycin
      in humans.
AB  - BACKGROUND: Simvastatin is a HMG-CoA reductase Inhibitor and a substrate of
      CYP3A4. Clarithromycin is a commonly used macrolide antibiotics and a potent
      inhibitor of CYP3A4. When co-administered with simvastatin, clarithromycin can
      significantly increase simvastatin plasma concentration levels, thereby, increase
      the risk of rhabdomyolysis. At present, pharmacokinetic data of the interaction
      between both drugs are available. However, they are being used for semi
      quantitative application only, not for quantitative prediction. We aimed to
      develop a mathematical model describing a drug-drug interaction between
      simvastatin and clarithromycin in humans. METHODS: Selected pharmacokinetic
      interaction study was obtained from PubMed search. Concentration-time course data
      were subsequently extracted and used for model development. Compartmental
      pharmacokinetic interaction model was developed using Advanced Continuous
      Simulating Language Extreme (ACSLX), a FORTRAN language-based computer program.
      RESULTS: The drug-drug interaction between simvastatin and clarithromycin was
      modeled simultaneously with a parent-metabolite model for clarithromycin and a
      one-compartment model for simvastatin linked to its active form, simvastatin
      hydroxy acid. The simulated simvastatin concentrations obtained from the final
      model displayed satisfactory goodness of fit to the data from the literature.
      CONCLUSION: Our model could successfully describe concentration-time course of
      simvastatin-clarithromycin interaction. The resulting interaction model can be
      able to use for further development of a quantitative model predicting
      rhabdomyolysis occurrence in patients concurrently receiving simvastatin and
      clarithromycin.

PMID- 25571291
TI  - Antibody-based molecular communication for targeted drug delivery systems.
AB  - Antibody-based drug delivery systems (ADDS) are established as the most promising
      therapeutic methods for the treatment of human cancers and other diseases. ADDS
      are composed of small molecules (antibodies) that selectively bind to receptors
      (antigens) expressed by the diseased cells. In this paper, the Molecular
      Communication (MC) paradigm, where the delivery of molecules is abstracted as the
      delivery of information, is extended to be applied to the design and engineering
      of ADDS. The authors have previously developed a straightforward framework for
      the modeling of Particulate Drug Delivery Systems (PDDS) using nano-sized
      molecules. Here, the specificities of antibody molecules are taken into account
      to provide an analytical model of ADDS transport. The inputs of the MC model of
      PDDS are the geometric properties of the antibodies and the topology of the blood
      vessels where they are propagated. Numerical results show that the analytical MC
      model is in good agreement with finite-element simulations, and that the
      anisotropy is an important factor influencing ADDS. 

PMID- 25571292
TI  - A pharmacokinetic drug-drug interaction model of simvastatin and verapamil in
      humans.
AB  - BACKGROUND: Verapamil is a calcium channel blocker commonly used in treatments of
      hypertension. Verapamil and its active metabolite, norverapamil, are known to be
      CYP3A4 inhibitors. Co-administration of verapamil with CYP3A4 substrates can
      alter the pharmacokinetics of the substrates. Simvastatin, a commonly used HMG
      CoA reductase inhibitor for the treatment of hypercholesterolemia is extensively
      metabolized by CYP3A4. Therefore, concomitant use of simvastatin and verapamil
      can increase simvastatin plasma concentration levels, resulting in a higher risk
      of rhabdomyolysis, a serious adverse drug reaction. Even though, pharmacokinetic
      data regarding the interaction between both drugs have been published, their use
      is limited to semiquantitative applications. Therefore, we aimed to develop a
      mathematical model describing drug-drug interaction between simvastatin and
      verapamil in humans. METHODS: Eligible pharmacokinetic interaction study between
      simvastatin and verapamil in humans was selected from PubMed database. The
      concentration-time courses from this study were digitally extracted and used for
      model development. RESULTS: The drug-drug interaction between simvastatin and
      verapamil was modeled simultaneously with a two compartment model for verapamil
      with its active metabolite, norverapamil and a one compartment model for
      simvastatin with its active form, simvastatin hydroxy acid. The effects of
      verapamil and norverapamil on pharmacokinetics of simvastatin and its active
      form, simvastatin hydroxy acid were described by Michaelis-Menten equation.
      Simulated simvastatin and simvastatin hydroxy acid concentrations obtained from
      the final model produced a good fit to the dataset from a literature. The final
      model adequately describes pharmacokinetic interaction between simvastatin and
      verapamil which can be helpful in prediction of rhabdomyolysis in patients with
      concurrent use of these drugs.

PMID- 25571293
TI  - Pharmacokinetic modeling of simvastatin, nelfinavir and their interaction in
      humans.
AB  - BACKGROUND: Simvastatin, a commonly used HMG-CoA reductase inhibitor, is
      extensively metabolized by CYP3A4. Therefore, co-administration of simvastatin
      and CYP3A4 inhibitor can affect simvastatin pharmacokinetics. Nelfinavir, a
      protease inhibitor, and its major metabolite (M8) are known to be potent CYP3A4
      inhibitors. When simvastatin and nelfinavir are co-administered, simvastatin
      pharmacokinetics is significantly altered and may result in an increased risk of
      rhabdomyolysis. OBJECTIVE: To develop a mathematical model describing a drug-drug
      interaction between simvastatin and nelfinavir in humans. METHODS: Eligible
      pharmacokinetic studies were selected from Pubmed database and concentration time
      course data were digitally extracted and used for model development.
      Compartmental pharmacokinetic models for simvastatin and nelfinavir were
      developed separately. A drug-drug interaction model of simvastatin and nelfinavir
      was subsequently developed using the prior information. Finally, the final drug
      drug interaction modeled was validated against observed simvastatin
      concentrations. RESULTS: Three compartmental pharmacokinetic models were
      successfully developed. Simvastatin pharmacokinetics was best described by a one
      compartment model for simvastatin linked to its active form, simvastatin hydroxy
      acid. Nelfinavir pharmacokinetics could be adequately described by a one
      compartment parent-metabolite model. Our final drug-drug interaction model
      predicted an increase in simvastatin exposure which is in line with clinical
      observations linking the simvastatin-nelfinavir combination to an increased risk
      of rhabdomyolysis. CONCLUSION: Simvastatin-nelfinavir pharmacokinetic interaction
      can be explained by our final model. This model framework will be useful in
      further advanced developing other mechanism based drug-drug interaction model
      used to predict the risk of rhabdomyolysis occurrence in patients prescribed
      simvastatin and nelfinavir concurrently.

PMID- 25571294
TI  - Heart rate variability as an indicator for morphine pharmacokinetics and
      pharmacodynamics in critically ill newborn infants.
AB  - Morphine is the commonest drug used for analgesia in newborn infants. It is a
      natural opioid that acts as an agonist at the mu and kappa receptors, which are
      receptors for analgesia and sedation. Morphine pharmacokinetics and
      pharmacodynamics (PKPD) for the newborn infant population are not well
      understood. The objective of this study is to use morphine PKPD parameters to
      estimate morphine plasma concentrations to be correlated with heart rate
      variability in the neonatal population. 

PMID- 25571295
TI  - Real-time dangling objects sensing: A preliminary design of mobile headset
      ancillary device for visual impaired.
AB  - Blinds and severe visual impairments can utilize tactile sticks to assist their
      walking. However, they cannot fully understand the dangling objects in front of
      their walking routes. This research proposed a mobile real-time dangling objects
      sensing (RDOS) prototype, which is located on the cap to sense any front barrier.
      This device utilized cheap ultrasonic sensor to act as another complement eye for
      blinds to understand the front dangling objects. Meanwhile, the RDOS device can
      dynamically adjust the sensor's front angle that is depended on the user's body
      height and promote the sensing accuracy. Meanwhile, two major required
      algorithms, height-angle measurement and ultrasonic sensor alignment, are
      proposed with this prototype. The research team also integrated the RDOS device
      prototype with mobile Android devices by communicating with Bluetooth to record
      the walking route. 

PMID- 25571296
TI  - Estimation of the patient monitor alarm rate for a quantitative analysis of new
      alarm settings.
AB  - In many critical care units, default patient monitor alarm settings are not fine
      tuned to the vital signs of the patient population. As a consequence there are
      many alarms. A large fraction of the alarms are not clinically actionable, thus
      contributing to alarm fatigue. Recent attention to this phenomenon has resulted
      in attempts in many institutions to decrease the overall alarm load of clinicians
      by altering the trigger thresholds for monitored parameters. Typically, new alarm
      settings are defined based on clinical knowledge and patient population norms and
      tried empirically on new patients without quantitative knowledge about the
      potential impact of these new settings. We introduce alarm regeneration as a
      method to estimate the alarm rate of new alarm settings using recorded patient
      monitor data. This method enables evaluation of several alarm setting scenarios
      prior to using these settings in the clinical setting. An expression for the
      alarm rate variance is derived for the calculation of statistical confidence
      intervals on the results. 

PMID- 25571297
TI  - An MR-compatible force sensor based on FBG technology for biomedical application.
AB  - Fiber Bragg Grating (FBG) technology is very attractive to develop sensors for
      the measurement of thermal and mechanical parameters in biological applications,
      particularly in presence of electromagnetic interferences. This work presents the
      design, working principle and experimental characterization of a force sensor
      based on two FBGs, with the feature of being compatible with Magnetic Resonance.
      Two prototypes based on different designs are considered and characterized: 1)
      the fiber with the FBGs is encapsulated in a polydimethylsiloxane (PDMS) sheet;
      2) the fiber with the FBGs is free without the employment of any polymeric layer.
      Results show that the prototype which adopts the polymeric sheet has a wider
      range of measurement (4200 mN vs 250 mN) and good linearity; although it has
      lower sensitivity (~0.1 nm-N(1) vs 7 nm-N(1)). The sensor without polymeric layer
      is also characterized by employing a differential configuration which allows
      neglecting the influence of temperature. This solution improves the linearity of
      the sensor, on the other hand the sensitivity decreases. The resulting good
      metrological properties of the prototypes here tested make them attractive for
      the intended application and in general for force measurement during biomedical
      applications in presence of electromagnetic interferences. 

PMID- 25571298
TI  - A reconfigurable parallel acceleration platform for evaluation of permutation
      entropy.
AB  - In recent years, permutation entropy is widely used to characterize the
      complexity of EEG time series and can be applied to predict the onset of serious
      brain diseases, such as the epileptic seizure. In many practical situations, the
      number of EEG time series that need to be analyzed simultaneously is very large,
      so the computation of the permutation entropy is time-consuming and should be
      accelerated so that the real-time analysis is possible. Noting that mathematical
      operations can be sped up effectively with hardware implementation, we design a
      parallel FPGA platform consisting of 128 reconfigurable pipelines, which are used
      to calculate the permutation entropy for a single EEG time series. When the
      platform works at 150MHz and the embedding dimension is 5, an average speedup of
      5553 for different window sizes is achieved compared with C codes running on a
      3GHz Intel(R) Core(TM) i5-2320 CPU. Meanwhile, the hardware cost is very low. 

PMID- 25571299
TI  - Quantifying saccades while walking: validity of a novel velocity-based algorithm
      for mobile eye tracking.
AB  - We validate a novel algorithm to detect saccades from raw data obtained during
      walking from a mobile infra-red eye-tracking device. The algorithm was based on a
      velocity threshold detection method, which excluded artefacts such as blinks and
      flickers using specific criteria. Mobile infra-red eye-tracking was performed
      with a group of healthy older adults (n=5) and Parkinson's disease (n=5)
      subjects. Saccades determined from raw eye tracker data obtained during walking
      using the algorithm were compared to a ground truth dataset defined as frame-by
      frame visual inspection of raw eye-tracking videos. 100 trials from 10 subjects
      were analyzed and compared. The algorithm was highly reliable when compared to
      the ground truth (ICC(2,1) = 0.94), with an overall correct saccade detection
      percentage of 85%. This provides a simple yet robust algorithm for the analysis
      of mobile eye-tracking data. 

PMID- 25571300
TI  - A passive quantitative measurement of airway resistance using depth data.
AB  - The Respiratory Syncytial Virus (RSV) is the most common cause of serious lower
      respiratory tract infections in infants and young children. RSV often causes
      increased airway resistance, clinically detected as wheezing by chest
      auscultation. In this disease, expiratory flows are significantly reduced due to
      the high resistance in patient's airway passages. A quantitative method for
      measuring resistance can have a great benefit to diagnosis and management of
      children with RSV infections as well as with other lung diseases. Airway
      resistance is defined as the lung pressure divided by the airflow. In this paper,
      we propose a method to quantify resistance through a simple, non-contact
      measurement of chest volume that can act as a surrogate measure of the lung
      pressure and volumetric airflow. We used depth data collected by a Microsoft
      Kinect camera for the measurement of the lung volume over time. In our
      experimentation, breathing through a number of plastic straws induced different
      airway resistances. For a standard spirometry test, our volume/flow estimation
      using Kinect showed strong correlation with the flow data collected by a
      commercially-available spirometer (five subjects, each performing 20 breathing
      trials, correlation coefficient = 0.88, with 95% confidence interval). As the
      number of straws decreased, emulating a higher airway obstruction, our algorithm
      was sufficient to distinguish between several levels of airway resistance. 

PMID- 25571301
TI  - A wrist-worn biosensor system for assessment of neurological status.
AB  - EEG based monitoring for the purpose of assessing a patient's neurological status
      is conspicuous and uncomfortable at best. We are analyzing a set of physiological
      signals that may be monitored comfortably by a wrist worn device. We have found
      that these signals and machine based classification allows us to accurately
      discriminate among four stress states of individuals. Further, we have found a
      clear change in these signals during the 70 minutes preceding a single convulsive
      epileptic seizure. Our classification accuracy on all data has been greater than
      90% to date. 

PMID- 25571302
TI  - An automatized system for the assessment of nutritive sucking behavior in
      infants: a preliminary analysis on term neonates.
AB  - Nutritive Sucking (NS) is a highly organized process that can reflect infants'
      maturation during the early post-natal period. The assessment of NS may provide a
      sensitive means of evaluating early motor skills and their development. Thus, a
      reliable tool for assessing sucking behavior may benefit diagnostics and
      treatment of newborns since the first days of life. The aim of this work is to
      propose an automatized system to measure sucking ability and calculate a set of
      objective and quantitative indices for its assessment. We focused on the analysis
      of the Intraoral Pressure (IP) generated by infants while feeding: an ad-hoc
      designed software application was developed to analyze the signal obtained by a
      pressure transducer connected with a catheter placed through a standard bottle
      teat into the oral cavity during feeding. Automatic algorithms for suck and burst
      identification and for their characterization are described. We carried out a
      preliminary test of the system, analyzing data from two healthy term newborns,
      tested twice over time (1-2 days old and 6-10 weeks later). We calculated a set
      of different sucking parameters (e.g. sucking amplitude, frequency and area), and
      proposed some indices, that are typically used for the assessment of motor
      control, in order to assess the smoothness of IP. Results encourage further
      investigation of the proposed system for monitoring the development of early
      sucking skills. 

PMID- 25571303
TI  - Real-time processing of electromyograms in an automated hand-forearm ergometer
      data collection and analysis system.
AB  - An automated hand-forearm ergometer with realtime data analysis would be a
      helpful tool to evaluate muscle fatigue mid-experiment, offering insights into
      changes in electromyogram parameters that can be used to track fatigue in the
      hand and forearm musculature. This work presents real-time additions to a custom,
      automated hand-forearm ergometer that will perform mid-experiment signal
      processing and help to identify fatigue onset and predict task failure. 

PMID- 25571304
TI  - Motion monitoring in palliative care using unobtrusive bed sensors.
AB  - Palliative care needs are growing with the aging population. Ambient sensors
      offer patients comfortable and discreet point-of-care monitoring. In this study,
      two palliative care participants were monitored in a sensorized bed. Motion
      monitoring by a two-tier gross and fine movement detector provided accurate
      detection and classification of movement, compared to annotations by an observer.
      However, ascribing the motion to the patient rather than caregivers or visitors
      would require supplemental sensors. Motion was indicative of pain, with 13% of
      time spent moving while in pain versus 3% while not noted as in pain. 

PMID- 25571305
TI  - Parkinson's disease detection using olfactory loss and REM sleep disorder
      features.
AB  - In Parkinson's disease, there exists a prodromal or a premotor phase
      characterized by symptoms like olfactory loss and sleep disorders, which may last
      for years or even decades before the onset of motor clinical symptoms. Diagnostic
      tools based on machine learning using these features can be very useful as they
      have the potential in early diagnosis of the disease. In the paper, we use
      olfactory loss feature from 40-item University of Pennsylvania Smell
      Identification Test (UPSIT) and Sleep behavior disorder feature from Rapid eye
      movement sleep Behavior Disorder Screening Questionnaire (RBDSQ), obtained from
      the Parkinson's Progression Marker's Initiative (PPMI) database, to develop
      automated diagnostic models using Support Vector Machine (SVM) and classification
      tree methods. The advantage of using UPSIT and RBDSQ is that they are quick,
      cheap, and can be self-administered. Results show that the models performed with
      high accuracy and sensitivity, and that they have the potential to aid in early
      diagnosis of Parkinson's disease. 

PMID- 25571306
TI  - An evaluation of exhaled flow measuring mouthpieces for breath sampling devices.
AB  - A study is conducted to determine the dimensions of an exhaled flow measuring
      mouthpiece for a breath-sampling device that requires breathing for an extended
      period of time. Fleisch, Pitot and Venturi type differential pressure based flow
      measuring mouthpieces of various dimensions are evaluated. Inner diameters (IDs)
      of the cylinder shaped Fleisch, Pitot and Venturi mouthpieces are varied from 5mm
      to 25mm. Based on the study, we conclude IDs ranging from 8.75mm to 12.5mm for
      Fleisch type, IDs ranging from 10mm to 12.5mm for Pitot type and ID of 10mm for
      Venturi type are the most suitable dimensions for a breath sampling device. 

PMID- 25571307
TI  - A stretchable and flexible system for skin-mounted measurement of motion tracking
      and physiological signals.
AB  - In this paper, we present a stretchable wearable system capable of i) measuring
      multiple physiological parameters and ii) transmitting data via radio frequency
      to a smart phone. The electrical architecture consists of ultra thin sensors (<;
      20 MUm thick) and a conformal network of associated active and passive
      electronics in a mesh-like geometry that can mechanically couple with the
      curvilinear surfaces of the human body. Spring-like metal interconnects between
      individual chips on board the device allow the system to accommodate strains
      approaching ~30% A representative example of a smart patch that measures movement
      and electromyography (EMG) signals highlights the utility of this new class of
      medical skin-mounted system in monitoring a broad range of neuromuscular and
      cardiovascular diseases. 

PMID- 25571308
TI  - High density wireless EEG prototype: Design and evaluation against reference
      equipment.
AB  - A high density wireless electroencephalographic (EEG) platform has been designed.
      It is able to record up to 64 EEG channels with electrode to tissue impedance
      (ETI) monitoring. The analog front-end is based on two kinds of low power ASICs
      implementing the active electrodes and the amplifier. A power efficient
      compression algorithm enables the use of continuous wireless transmission of data
      through Bluetooth for real-time monitoring with an overall power consumption of
      about 350 mW. EEG acquisitions on five subjects (one healthy subject and four
      patients suffering from epilepsy) have been recorded in parallel with a reference
      system commonly used in clinical practice and data of the wireless prototype and
      reference system have been processed with an automatic tool for seizure detection
      and localization. The false alarm rates (0.1-0.5 events per hour) are comparable
      between the two system and wireless prototype also detected the seizure correctly
      and allowed its localization. 

PMID- 25571309
TI  - Data sample size needed for prediction of movement distributions.
AB  - Human movement ability should be described not only by its typical behavior, but
      also by the wide variation in capabilities. This would mean that subjects that
      are encouraged to move throughout their workspace but otherwise free to move any
      way they like might reveal their unique movement tendencies. In this study, we
      investigate how much information (data) is needed to reliably construct a
      movement distribution that predicts an individual's movement tendencies. We
      analyzed the distributions of position, velocity and acceleration data derived
      during self-directed motor exploration by stroke survivors (n=10 from a previous
      study) and healthy individuals (n=5). We examined whether these simple kinematic
      variables differed in terms of the amount of data required. We found a trend of
      decreasing time needed for characterization with the order of kinematic variable,
      for position, velocity, and acceleration, respectively. In addition, we
      investigated whether data requirements differ between stroke survivors and
      healthy. Our results suggest that healthy individuals may require more data
      samples (time for characterization), though the trend was only significant for
      position data. Our results provide an important step towards using statistical
      distributions to describe movement tendencies. Our findings could serve as more
      comprehensive tools to track recovery in or design more focused training
      intervention in neurorehabiliation applications. 

PMID- 25571310
TI  - Pilot study on quantitative assessment of muscle imbalance: differences of muscle
      synergies, equilibrium-point trajectories, and endpoint stiffness in normal and
      pathological upper-limb movements.
AB  - This paper proposes a novel method for assessment of muscle imbalance based on
      muscle synergy hypothesis and equilibrium point (EP) hypothesis of motor control.
      We explain in detail the method for extracting muscle synergies under the concept
      of agonist-antagonist (AA) muscle pairs and for estimating EP trajectories and
      endpoint stiffness of human upper limbs in a horizontal plane using an
      electromyogram. The results of applying this method to the reaching movement of
      one normal subject and one hemiplegic subject suggest that (1) muscle synergies
      (the balance among coactivation of AA muscle pairs), particularly the synergies
      that contributes to the angular directional kinematics of EP and the limb
      stiffness, are quite different between the normal subject and the hemiplegic
      subject; (2) the concomitant EP trajectory is also different between the normal
      and hemiplegic subjects, corresponding to the difference of muscle synergies; and
      (3) the endpoint (hand) stiffness ellipse of the hemiplegic subject becomes more
      elongated and orientation of the major axis rotates clockwise more than that of
      the normal subject. The level of motor impairment would be expected to be
      assessed from a comparison of these differences of muscle synergies, EP
      trajectories, and endpoint stiffness among normal and pathological subjects using
      the method. 

PMID- 25571311
TI  - Sensorimotor cortex reorganization in subacute and chronic stroke: A
      neuronavigated TMS study.
AB  - The integrity of the corticospinal system is an important biomarker for recovery
      from stroke. However, mapping the topography of the corticospinal system in
      subacute stroke is not trivial and how it changes over the course of recovery is
      poorly understood. We intend to use a transcranial magnetic stimulation (TMS)
      based mapping approach to quantify the topographic landscape of corticospinal
      activation in the ipsi- and contralesional sensorimotor cortices in the subacute
      and chronic phase of stroke. Mapping was conducted before (PRE) and after (POST),
      intervention in 10 chronic subjects and 8 subacute subjects. Reorganization was
      quantified in a unique way by dissociating reorganization attributed to changes
      in the expanse (area) of the sensorimotor territory, from that attributed to
      changes in the robustness of the activation (amplitude). In doing so, we observed
      differences in reorganization in the subacute and chronic stages indicating that
      recovery in different stages may not be guided by similar neurophysiological
      mechanisms of neuroplasticity. 

PMID- 25571312
TI  - A testbed to explore the optimal electrical stimulation parameters for
      suppressing inter-ictal spikes in human hippocampal slices.
AB  - New interventions using neuromodulatory devices such as vagus nerve stimulation,
      deep brain stimulation and responsive neurostimulation are available or under
      study for the treatment of refractory epilepsy. Since the actual mechanisms of
      the onset and termination of the seizure are still unclear, most researchers or
      clinicians determine the optimal stimulation parameters through trial-and-error
      procedures. It is necessary to further explore what types of electrical
      stimulation parameters (these may include stimulation frequency, amplitude,
      duration, interval pattern, and location) constitute a set of optimal stimulation
      paradigms to suppress seizures. In a previous study, we developed an in vitro
      epilepsy model using hippocampal slices from patients suffering from mesial
      temporal lobe epilepsy. Using a planar multi-electrode array system, inter-ictal
      activity from human hippocampal slices was consistently recorded. In this study,
      we have further transferred this in vitro seizure model to a testbed for
      exploring the possible neurostimulation paradigms to inhibit inter-ictal spikes.
      The methodology used to collect the electrophysiological data, the approach to
      apply different electrical stimulation parameters to the slices are provided in
      this paper. The results show that this experimental testbed will provide a
      platform for testing the optimal stimulation parameters of seizure cessation. We
      expect this testbed will expedite the process for identifying the most effective
      parameters, and may ultimately be used to guide programming of new stimulating
      paradigms for neuromodulatory devices. 

PMID- 25571313
TI  - Early detection of human focal seizures based on cortical multiunit activity.
AB  - Approximately 50 million people in the world suffer from epileptic seizures.
      Reliable early seizure detection could bring significantly beneficial therapeutic
      alternatives. In recent decades, most approaches have relied on scalp EEG and
      intracranial EEG signals, but practical early detection for closed-loop seizure
      control remains challenging. In this study, we present preliminary analyses of an
      early detection approach based on intracortical neuronal multiunit activity (MUA)
      recorded from a 96-microelectrode array (MEA). The approach consists of (1) MUA
      detection from broadband field potentials recorded at 30 kHz by the MEA; (2) MUA
      feature extraction; (3) cost-sensitive support vector machine classification of
      ictal and interictal samples; and (4) Kalman-filtering postprocessing. MUA was
      here defined as the number of threshold crossing (spike counts) applied to the
      300 Hz-6 kHz bandpass filtered local field potentials in 0.1 sec time windows.
      MUA features explored in this study included the mean, variance, and Fano-factor,
      computed across the MEA channels. In addition, we used the leading eigenvalues of
      MUA spatial and temporal correlation matrices computed in 1-sec moving time
      windows. We assessed the seizure detection approach on out-of-sample data from
      one-participant recordings with six seizure events and 4.73-hour interictal data.
      The proposed MUA-based detection approach yielded a 100% sensitivity (6/6) and no
      false positives, and a latency of 4.17 +/- 2.27 sec (mean +/- SD) with respect to
      ECoG-identified seizure onsets. These preliminary results indicate intracortical
      MUA may be a useful signal for early detection of human epileptic seizures. 

PMID- 25571314
TI  - Unstable periodic orbits in human epileptic hippocampal slices.
AB  - Inter-ictal activity is studied in hippocampal slices resected from patients with
      epilepsy using local field potential recording. Inter-ictal activity in the
      dentate gyrus (DG) is induced by high-potassium (8 mM), low-magnesium (0.25 mM)
      aCSF with additional 100 MUM 4-aminopyridine(4-AP). The dynamics of the inter
      ictal activity is investigated by developing the first return map with inter
      pulse intervals. Unstable periodic orbits (UPOs) are detected in the hippocampal
      slice at the DG area according to both the topological recurrence method and the
      periodic orbit transform method. Surrogate analysis suggests the presence of UPOs
      in hippocampal slices from patients with epilepsy. This finding also suggests
      that inter-ictal activity is a chaotic system and will allow us to apply chaos
      control techniques to manipulate inter-ictal activity. 

PMID- 25571315
TI  - Constraints imposed by the lower extremity extensor synergy in chronic
      hemiparetic stroke: Preliminary findings.
AB  - In the present manuscript we implemented the MultiLEIT, a lower extremity
      isometric torque measurement device to quantify spontaneous joint torque coupling
      during maximal torque generation in the paretic leg of in chronic hemiparetic
      stroke. We quantified extension/adduction coupling (coincident with the clinical
      extension synergy) during the generation of hip extension and ankle
      plantarflexion maximum voluntary torques. Subjects were then instructed to
      generate torques outside the synergy by combining hip extension+ hip abduction or
      ankle plantarflexion + hip abduction. During the hip dual task, the paretic hip
      torques were significantly different from those measured in the non-paretic and
      control leg (F = 22.9719, p = 0) and resulted in the inability to generate
      torques outside the extensor synergy patters. During the dual ankle/ hip task,
      the paretic extremity generated significantly smaller hip abduction torques
      compared to controls and to the non-paretic extremity (F = 15.861, p = 0). During
      this task the paretic extremity was capable of neutralizing the spontaneous
      adduction torque and generate a net albeit small abduction torque. Results may
      indicate an increased descending drive from brain stem pathways, particularly
      during hip extension, responsible for constraints in generating hip abduction
      torques after stroke. 

PMID- 25571316
TI  - Increased shoulder abduction loads decreases volitional finger extension in
      individuals with chronic stroke: Preliminary findings.
AB  - The ability to open the paretic hand is greatly affected after a stroke. The loss
      of especially finger extension has been previously reported during isolated
      finger movements. However, activities of daily life require the combination of
      reaching and grasping which will require shoulder abduction. Shoulder abductor
      activity will result in concurrent elbow, wrist and finger flexion which is also
      referred to as the flexion synergy. Therefore as part of this study the effect of
      of shoulder abduction (SABD) loading on volitional finger extension in
      individuals with chronic stroke is investigated. We expect to observe that
      shoulder abduction loading will further decrease the already impaired volitional
      finger extension in individuals with chronic stroke. A total of four moderately
      impaired individuals with chronic stroke and three age-matched able-bodied
      subjects participated in this study. Finger extension was recorded during hand
      open while subjects kept their arm extended at the end of a reach. The
      preliminary data showed that the maximal volitional finger extension was
      significantly decreased by increasing the SABD loads in individuals with chronic
      stroke, but not in age-matched able-bodied subjects. 

PMID- 25571317
TI  - Computing network-based features from intracranial EEG time series data:
      Application to seizure focus localization.
AB  - The surgical resection of the epileptogenic zone (EZ) is the only effective
      treatment for many drug-resistant epilepsy (DRE) patients, but the pre-surgical
      identification of the EZ is challenging. This study investigates whether the EZ
      exhibits a computationally identifiable signature during seizures. In particular,
      we compute statistics of the brain network from intracranial EEG (iEEG)
      recordings and track the evolution of network connectivity before, during, and
      after seizures. We define each node in the network as an electrode and weight
      each edge connecting a pair of nodes by the gamma band cross power of the
      corresponding iEEG signals. The eigenvector centrality (EVC) of each node is
      tracked over two seizures per patient and the electrodes are ranked according to
      the corresponding EVC value. We hypothesize that electrodes covering the EZ have
      a signature EVC rank evolution during seizure that differs from electrodes
      outside the EZ. We tested this hypothesis on multi-channel iEEG recordings from 2
      DRE patients who had successful surgery (i.e., seizures were under control with
      or without medications) and 1 patient who had unsuccessful surgery. In the
      successful cases, we assumed that the resected region contained the EZ and found
      that the EVC rank evolution of the electrodes within the resected region had a
      distinct "arc" signature, i.e., the EZ ranks first rose together shortly after
      seizure onset and then fell later during seizure. 

PMID- 25571319
TI  - Evaluation of the performance of an experimental somnolence quantification system
      in terms of reaction times and lapses.
AB  - Somnolence is known to be a major cause of various types of accidents, and ocular
      parameters are recognized to be reliable physiological indicators of somnolence.
      We have thus developed an experimental somnolence quantification system that uses
      images of the eye and that produces a level of somnolence on a continuous
      numerical scale. The aim of this paper is to show that the level of somnolence
      produced by our system is well related to the level of performance of subjects
      accomplishing three reaction-time tests in different sleep conditions. Twenty
      seven subjects participated in the study and images of their right eye were
      continuously recorded during the tests. Levels of somnolence, reaction times
      (RTs), and percentages of lapses were computed for each minute of test. Results
      show that the values of these three parameters increase significantly with sleep
      deprivation. We determined the best threshold on our scale of somnolence to
      predict lapses, and we also shown that correlations exist with some of the ocular
      parameters. Our somnolence quantification system has thus significant potential
      to predict performance decrements of subjects accomplishing a task. 

PMID- 25571318
TI  - Smart adaptable system for older adults' Daily Life Activities Management - The
      ABLE platform.
AB  - In this paper we propose a system (ABLE) that will act as the main platform for a
      number of low-cost, mature technologies that will be integrated in order to
      create a dynamically adaptive Daily Life Activities Management environment in
      order to facilitate the everyday life of senior (but not exclusively) citizens at
      home. While the main target group of ABLE's users is the ageing population its
      use can be extended to all people that are vulnerable or atypical in body,
      intellect or emotions and are categorized by society as disabled. The classes of
      assistive products that are well defined in the international standard, ISO9999
      such as assistive products for personal medical treatment, personal care and
      protection, communication, information and reaction and for personal mobility,
      will be easily incorporated in our proposed platform. Furthermore, our platform
      could integrate and implement the above classes under several service models that
      will be analyzed further. 

PMID- 25571320
TI  - Mechanomyography energy decreases during muscular fatigue in paraplegics.
AB  - The present work investigated the response of triaxial MMG signals acquired from
      the rectus femoris muscle of spinal cord injured volunteers during fatigue
      protocol electrically evoked. A custom functional electrical stimulator voltage
      controlled was configured as: pulse frequency set to 1 kHz (20% duty cycle) and
      burst (modulating) frequency set to 70 Hz (20% active period). The triaxial MMG
      signal of rectus femoris muscle was processed with third-order 5-50 Hz bandpass
      Butterworth filter and the values were normalized. A load cell was used to
      register the force. The stimulator output voltage was increased until the maximal
      electrically-evoked extension (MEEE) of knee joint. After the load cell
      placement, the stimuli magnitude required to reach the MEEE was applied and
      registered by the load cell as muscular force-100% response. Stimuli intensity
      was increased until and during the control to keep the force in force-100%. Four
      instants with force functional electrical stimulation (FES)-controlled were
      selected between force-100% and slope down to force-30%. The MMG energy decreased
      with FES application due neuromuscular fatigue in paraplegic subjects. X-axis
      between instant I (1 +/- 0) and instant IV (0.74 +/- 0.27), and the same tendency
      was found to Y-axis between instant II (1.14 +/- 0.44) and instant IV (0.91 +/-
      0.3).

PMID- 25571321
TI  - A preliminary study on evaluation of circumduction movement during gait with
      wireless inertial sensors.
AB  - Recently, inertial sensors have been used to measure human movements for the
      purpose of rehabilitation. In evaluation of motor function for rehabilitation,
      reference data measured from healthy subjects with inertial sensors is needed. In
      addition, since lower limbs perform 3-dimensional movements during gait, it is
      needed to analyze 3-dimensional gait movements. The plot of 3-dimensional vector
      locus can be useful to understand 3-dimensional movements. The purposes of this
      paper were to show usefulness of the vector locus in understanding circumduction
      during gait, and to test an evaluation parameter for 3-dimensional movements
      during walking as reference data. Gait of 12 healthy subjects were measured, and
      then vector loci were plotted in the 3-dimensional space. Shape of the vector
      locus was evaluated by the width of each component as one of the reference data.
      It was suggested that the vector loci plotted in 3-dimensioinal space or those
      projected on horizontal plane were useful to understand circumduction during
      gait. It was also suggested that the width of vector locus was useful to evaluate
      differences of movement between subjects. 

PMID- 25571322
TI  - An indirect method to estimate the force output of triceps surae muscle.
AB  - Estimation of force output generated by human muscle is an essential routine of
      clinical rehabilitation assessment, and could provide considerable insight into
      rehabilitation, motor control and robotics. Indirect methods for the estimation
      of force output could be helpful when a bulky and expensive dynamometer is not on
      hand. Electromyography has been used in previous studies to quantify it in the
      literature. However, the force output is a summation of the motor unit action
      potentials, and thus the contributions and performances of superficial and deep
      lying muscles could hardly be separated from each other. In this preliminary
      study, we applied ultrasonography (US) to explore the feasibility of estimating
      triceps surae force output during isometric plantar flexion with spatial
      resolution from superficial to deeper muscles. The local deformations of US
      images are extracted to represent the morphological changes during force
      generation. It was found US could be utilized to decently (coefficient of
      determination at 0.875 +/- 0.051 and normalized root mean square error 0.160 +/-
      0.035) estimate the force output and the measured force by a dynamometer. 

PMID- 25571323
TI  - Quantification of human movement for assessment in automated exercise coaching.
AB  - Quantification of human movement is a challenge in many areas, ranging from
      physical therapy to robotics. We quantify of human movement for the purpose of
      providing automated exercise coaching in the home. We developed a model-based
      assessment and inference process that combines biomechanical constraints with
      movement assessment based on the Microsoft Kinect camera. To illustrate the
      approach, we quantify the performance of a simple squatting exercise using two
      model-based metrics that are related to strength and endurance, and provide an
      estimate of the strength and energy-expenditure of each exercise session. We look
      at data for 5 subjects, and show that for some subjects the metrics indicate a
      trend consistent with improved exercise performance. 

PMID- 25571324
TI  - An approach to measure wheelchair stability. Concept and benefits.
AB  - Wheelchair stability is dependent on user's body characteristics that can shift
      significantly the original center of mass in the cases of limb amputation, severe
      skeletal deformities or obesity. The center of gravity may change with the
      installation of additional devices such as oxygen cylinders or ventilators on the
      wheelchair. Therefore, quantitative evaluation and prediction of the behavior of
      the user-wheelchair system in a variety of static and dynamic situations is
      essential for user's safety and for the optimal tuning of the human-wheelchair
      system. In this paper we discuss an approach for wheelchair stability assessment
      that only requires two inclinations and weight measurements. We also discuss the
      algorithm associated to the procedure based on the use of the reaction forces in
      the contact points of the wheels measured by the load cells. Further, the paper
      includes an analysis of the influence of the errors in measurement of the input
      parameters on the output results and demonstrates that the proposed approach
      possesses high accuracy. The advantage of the proposed approach is the use of a
      reliable procedure based on three simple steps and five weight measurements with
      four independent load scales which may lead to the design of an affordable and
      accurate measurement system. 

PMID- 25571325
TI  - Slacking in the context of agent-based assessment in virtual rehabilitation
      systems.
AB  - Efforts are already underway to develop technology-derived solutions which
      automate aspects of conventional therapy. Ideally we would like to develop a
      human-like virtual therapist, in an attempt to enhance automated rehabilitation
      particularly in the home setting. One interesting skill of the experienced human
      therapist that we would like to model is the ability to recognize and manage
      behavior patterns known to decrease the effectiveness of rehabilitation. A
      particularly compelling example of such behavior is described in the context of
      robot-assisted therapy, where it has been demonstrated that "assist-as-needed"
      strategies may impact negatively on rehabilitation outcomes due to an intrinsic
      property of the human motor systems that encourages "slacking" as a form of
      energy optimization. In this work we endeavor to explore and extend this concept
      by giving it context in the standard therapist-patient interaction setting. We
      developed an apparatus which can measure and quantify grip strength and an agent
      based virtual therapist that can assess performance and offer simple natural
      language feedback in real time. We then conducted a series of experiments with
      healthy subjects in which the mapping between performance and feedback valence is
      altered. Our results demonstrate that subject performance is dependent on the
      feedback rules and that in particular, excessively positive feedback yields
      performance dynamics analogous to those observed in slacking studies. These
      preliminary results have implications for the design of virtual therapist
      systems. 

PMID- 25571326
TI  - Surface electromyographic control of speech synthesis.
AB  - Individuals with very high spinal cord injuries (e.g. C1-C3) may be ventilator
      dependent and therefore unable to support speech breathing. However, their facial
      musculature is intact, given that these muscles are innervated by cranial nerves.
      We developed a system using surface electromyography (sEMG) recorded from facial
      muscles to control a phonemic interface and voice synthesizer and tested the
      system in healthy individuals. Users were able to use five facial gestures to
      control an onscreen cursor and the phonemic interface. Users had mean information
      transfer rates (ITRs) of 59.5 bits/min when calculating ITRs using the number of
      phonemes selected. To compare with orthographic systems, ITRs were also
      calculated using the equivalent number of letters required to spell the selected
      word. With this calculation, users had a mean ITR of 70.1. Results are promising
      for further development and testing in individuals with high spinal cord
      injuries. 

PMID- 25571327
TI  - Designing auditory cues for Parkinson's disease gait rehabilitation.
AB  - Recent works have proved that Parkinson's disease (PD) patients can be largely
      benefit by performing rehabilitation exercises based on audio cueing and music
      therapy. Specially, gait can benefit from repetitive sessions of exercises using
      auditory cues. Nevertheless, all the experiments are based on the use of a
      metronome as auditory stimuli. Within this work, Human-Computer Interaction
      methodologies have been used to design new cues that could benefit the long-term
      engagement of PD patients in these repetitive routines. The study has been also
      extended to commercial music and musical pieces by analyzing features and
      characteristics that could benefit the engagement of PD patients to
      rehabilitation tasks. 

PMID- 25571328
TI  - EEG-based event detection using optimized echo state networks with leaky
      integrator neurons.
AB  - This study investigates the classification ability of linear and nonlinear
      classifiers on biological signals using the electroencephalogram (EEG) and
      examines the impact of architectural changes within the classifier in order to
      enhance the classification. Consequently, artificial events were used to validate
      a prototype EEG-based microsleep detection system based around an echo state
      network (ESN) and a linear discriminant analysis (LDA) classifier. The artificial
      events comprised infrequent 2-s long bursts of 15 Hz sinusoids superimposed on
      prerecorded 16-channel EEG data which provided a means of determining and
      optimizing the accuracy of overall classifier on 'gold standard' events. The
      performance of this system was tested on different signal-to-noise amplitude
      ratios (SNRs) ranging from 16 down to 0.03. Results from several feature
      selection/reduction and pattern classification modules indicated that training
      the classifier using a leaky-integrator neuron ESN structure yielded highest
      classification accuracy. For datasets with a low SNR of 0.3, training the leaky
      neuron ESN using only those features which directly correspond to the underlying
      event, resulted in a phi correlation of 0.92 compared to 0.37 that employed
      principal component analysis (PCA). On the same datasets, other classifiers such
      as LDA and simple ESNs using PCA performed weakly with a correlation of 0.05 and
      0 respectively. These results suggest that ESNs with leaky neuron architectures
      have superior pattern recognition properties. This, in turn, may reflect their
      superior ability to exploit differences in state dynamics and, hence, provide
      superior temporal characteristics in learning. 

PMID- 25571329
TI  - Brain biomarkers based assessment of cognitive workload in pilots under various
      task demands.
AB  - Cognitive workload is an important element of cognitive-motor performance such as
      that exhibited during the piloting of an aircraft. Namely, an increase in task
      demands on the pilot can elevate cognitive information processing and, thus, the
      risk of human error. As such, there is a need to develop methods that reliably
      assess mental workload in pilots within operational settings. The present study
      contributes to this research goal by identifying physiological and brain
      biomarkers of cognitive workload and attentional reserve during a simulated
      aircraft piloting task under three progressive levels of challenge. A newly
      developed experimental method was employed by which electroencephalography (EEG)
      was acquired via a dry (i.e., gel-free sensors) system using few scalp sites.
      Self-reported responses to surveys and piloting performance indicators were
      analyzed. The findings revealed that as the challenge (task demands) increased,
      the perceived mental load increased, attentional reserve was attenuated, and task
      performance decreased. Such an increase in task demands was also reflected by
      changes in heart rate variability (HRV), as well as in the amplitude of the P300
      component of event-related potentials to auditory probes, and in the spectral
      power of specific EEG frequency bands. This work provides a first step towards a
      long-term goal to develop a composite system of biomarkers for real-time
      cognitive workload assessment and state assessment of pilots in operational
      settings. 

PMID- 25571330
TI  - Effects of contraction path and velocity on the coordination of hand muscles
      during a three-digit force production task.
AB  - Though many studies indicated that the behavior of single muscle was different
      between contraction and relaxation, the effect of contraction history profile on
      multiple muscles has not been investigated. In this study, we analyzed the
      influence of contraction history on the coordination patterns of hand muscles
      during a three-digit force production task. The effects of the contraction and
      relaxation paths with two contraction velocities (5% and 10% maximum voluntary
      contraction per second) were investigated. The results showed that the force
      independent characteristic of muscle coordination patterns still held regardless
      of the contraction history profiles. In addition, the effect of contraction path
      was more significant than that of velocity. The study provides a potential way to
      overcome the impact of contraction disturbance for improving the robustness of
      the human-machine interface (HMI) based on electromyographic (EMG) pattern
      recognition. 

PMID- 25571331
TI  - A simple calibration for upper limb motion tracking and reconstruction.
AB  - This paper extends the work of inertial sensor based upper limb motion tracking
      by introducing a simple calibration method to automatically construct a global
      reference frame and estimate arm length. The method has effectively eliminated
      the requirement of manually aligning the sensors' local reference frames when
      multiple sensors are used to track the movements of the individual arm segments.
      The capacity of arm length estimation also makes it possible to reconstruct
      position trajectories of the elbow and the wrist joints in a reference frame with
      the shoulder joint as the origin. Verification of the algorithm has been done by
      comparing the estimated arm length with the Kinect captured pseudo ground truth.
      Effectiveness of the algorithm can be observed by visualizing the reconstructed
      position trajectories of the arm joints. 

PMID- 25571332
TI  - Variability in responsiveness to interventions in people with spinal cord injury:
      Do some respond better than others?
AB  - Spinal cord injury (SCI) results in significant impairments in function and ankle
      joint spasticity is a common secondary complication. Various interventions have
      been trialed to improve function and reduce spasticity after SCI, with variable
      results. We investigated the effects of a pharmacological (an anti-spastic
      medication - tizanidine) and a physical intervention (robotic-assisted locomotor
      training - Lokomat) on function in people with incomplete SCI over 4-week of
      training. The outcome measures were walking speed, endurance and mobility.
      Subjects were randomized into one of three groups; no intervention (control),
      Lokomat (Lok) and tizanidine (Tiz). To account for variability, we used growth
      mixture modelling (GMM) to class subjects based on their recovery patterns. GMM
      identified two classes of recovery: high and low function. Significant
      improvements were seen in walking speed and mobility in high and low functioning
      subjects in the Lok group, and in walking endurance in high functioning subjects
      in the Tiz group. However, changes with training were clinically important only
      for approximately 10% of subjects, who achieved a minimal important difference
      (MID) in functional outcomes as a result of the training. We used mixed model
      ANOVAs to compare the group effects. Improvements with training were seen in both
      classes, however no differences between interventions were found. The GMM had
      classed all subjects that achieved the MID as high functioning. GMM can be used
      to successfully class subjects; however larger subject numbers and longer
      interventions are required to fully utilize this technique. Our results
      demonstrate that both interventions have potential to improve walking capacity,
      but more intense training for a longer period may need to achieve MID. 

PMID- 25571333
TI  - Judging hardness of an object from the sounds of tapping created by a white cane.
AB  - The white cane plays a vital role in the independent mobility support of the
      visually impaired. Allowing the recognition of target attributes through the
      contact of a white cane is an important function. We have conducted research to
      obtain fundamental knowledge concerning the exploration methods used to perceive
      the hardness of an object through contact with a white cane. This research has
      allowed us to examine methods that enhance accuracy in the perception of objects
      as well as the materials and structures of a white cane. Previous research
      suggest considering the roles of both auditory and tactile information from the
      white cane in determining objects' hardness is necessary. This experimental study
      examined the ability of people to perceive the hardness of an object solely
      through the tapping sounds of a white cane (i.e., auditory information) using a
      method of magnitude estimation. Two types of sounds were used to estimate
      hardness: 1) the playback of recorded tapping sounds and 2) the sounds produced
      on-site by tapping. Three types of handgrips were used to create different sounds
      of tapping on an object with a cane. The participants of this experiment were
      five sighted university students wearing eye masks and two totally blind students
      who walk independently with a white cane. The results showed that both sighted
      university students and totally blind participants were able to accurately judge
      the hardness of an object solely by using auditory information from a white cane.
      For the blind participants, different handgrips significantly influenced the
      accuracy of their estimation of an object's hardness. 

PMID- 25571334
TI  - Using S-transform in EEG analysis for measuring an alert versus mental fatigue
      state.
AB  - This paper presents research that investigated the effects of mental fatigue on
      brain activity using electroencephalogram (EEG) signals. Since EEG signals are
      considered to be non-stationary, time-frequency analysis has frequently been used
      for analysis. The S-transform is a time-frequency analysis method and is used in
      this paper to analyze EEG signals during alert and fatigue states during a
      driving simulator task. Repeated-measure MANOVA results show significant
      differences between alert and fatigue states within the alpha (8-13Hz) frequency
      band. The two sites demonstrating the greatest increases in alpha activity during
      fatigue were the Cz and P4 sites. The results show that S-transform analysis can
      be used to distinguish between alert and fatigue states in the EEG and also
      supports the use of the S-transform for EEG analysis. 

PMID- 25571335
TI  - A non-ZUPT gait reconstruction method for ankle sensors.
AB  - Monitoring lower body motion, especially gait pattern, using low cost Inertial
      Measurement Units on a daily basis is becoming critically important for the
      diagnosis and rehabilitation of neurological diseases. The current state of the
      art algorithm is to double integrate motion acceleration and compensate
      cumulative errors by resetting velocity signals to zero at the stance-phase of
      each stride. However, this method is only applicable for foot-mounted sensors.
      For the medically more preferable ankle-mounted position, the assumption of this
      zero-velocity-update (ZUPT) method does not hold. In this paper, a new non-ZUPT
      method is proposed. We estimated the true velocity during stance-phase, and reset
      velocity to the estimated value instead of zero. 10 subjects were recruited for
      40-meter-level flat floor walking. The stride length estimation error was reduced
      to 3.58% from 13.22% on average comparing to the conventional ZUPT method on an
      ankle-mounted sensor. Validity of this method is further supported by stairs
      walking of 4 more subjects. 

PMID- 25571336
TI  - Severity of spine malalignment on center of pressure progression during level
      walking in subjects with adolescent idiopathic scoliosis.
AB  - Center of pressure (CoP) progression during level walking in subjects with
      Adolescents Idiopathic Scoliosis (AIS) was measured. Participants were divided
      into three groups according to scoliosis severity. CoP progression among groups
      was compared quantitatively and qualitatively. The results showed that scoliosis
      severity affects CoP progression significantly in the hind-foot and forefoot
      areas. This result indicated that spine alignment might affect the control of
      heel, ankle and toe rockers in the ankle-foot complex. The effects of scoliosis
      severity is mainly on the CoP of right foot plantar surface, indicating
      asymmetrical influence of IS on bilateral lower limb coordination during walking.
      These results might contribute to musculoskeletal complains over the apparatus
      within trunk-foot in the later lives of this population. 

PMID- 25571337
TI  - Within trial validation and reliability of a single tri-axial accelerometer for
      gait assessment.
AB  - Gait is a sensitive biomarker of decline in both cognitive and physical function.
      Therefore, the collection of gait data is an important feature of clinical
      assessments. Accelerometer-based body worn sensors are quickly becoming the
      preferred tool for assessing gait because they are small, useable in a wide
      variety of settings, offer more continuous spatio-temporal analysis and are
      inexpensive when compared with traditional gait assessment methodologies. The
      purpose of this study was to determine the validity and within test reliability
      of a low cost body worn movement sensor with associated algorithms to assess gait
      in a large group of older and younger healthy adults. We collected gait data over
      intermittent walks on an instrumented walkway for a within trial validation and
      also used the same accelerometer derived gait data for a within test reliability
      analysis. ICCs for validation and reliability were >0.756 and >0.965,
      respectively. 

PMID- 25571338
TI  - Classifying and predicting endurance outcomes of alpha2-adrenergic agonist
      intervention in spinal cord injury.
AB  - Spinal cord injury (SCI) is a traumatic condition that can lead to both
      functional and neuromuscular impairments. Spasticity in the muscles surrounding
      the ankle joint caused by hypertonia is often reported as a complication. We
      investigated whether a pharmacological intervention using Tizanidine, an anti
      spastic medication acting as an alpha2-adrenergic agonist, could lead to
      improvements in walking endurance. We placed subjects on a 4-week program and
      measured the change in clinical measures of walking speed, endurance, and
      mobility. We used growth mixture modeling (GMM) to class subjects into groups
      based on recovery patterns. Two classes of recovery were found by GMM: high and
      low functioning. Radom coefficient regression (RCR) was then used to identify
      significant changes over time. Statistically significant improvements in walking
      endurance were shown for the high functioning group. However, a small number of
      subjects in the high functioning group showed improvement greater than the
      smallest real difference (SRD), which indicates a clinical significance as well.
      We also investigated the extent to which these recovery patterns can be predicted
      using baseline measures. Baseline walking endurance was found to be a robust
      predictor of recovery in walking endurance. Subjects that began the intervention
      with already higher endurance showed a greater chance of improvement in endurance
      over time. This information could potentially be used as a fast and reliable
      assessment tool for clinicians to predict which patient can benefit the most from
      this intervention prior to prescribing the medication, and thus optimizing cost
      and resources. Our findings demonstrate that these techniques can be used to
      characterize and predict the progress of changes to functional impairments due to
      various types of intervention. 

PMID- 25571339
TI  - Detection of patient's bed statuses in 3D using a Microsoft Kinect.
AB  - Patients spend the vast majority of their hospital stay in an unmonitored bed
      where various mobility factors can impact patient safety and quality.
      Specifically, bed positioning and a patient's related mobility in that bed can
      have a profound impact on risks such as pneumonias, blood clots, bed ulcers and
      falls. This issue has been exacerbated as the nurse-per-bed (NPB) ratio has
      decreased in recent years. To help assess these risks, it is critical to monitor
      a hospital bed's positional status (BPS). Two bed positional statuses, bed height
      (BH) and bed chair angle (BCA), are of critical interests for bed monitoring. In
      this paper, we develop a bed positional status detection system using a single
      Microsoft Kinect. Experimental results show that we are able to achieve 94.5% and
      93.0% overall accuracy of the estimated BCA and BH in a simulated patient's room
      environment. 

PMID- 25571340
TI  - Monitoring patients in hospital beds using unobtrusive depth sensors.
AB  - We present an approach for patient activity recognition in hospital rooms using
      depth data collected using a Kinect sensor. Depth sensors such as the Kinect
      ensure that activity segmentation is possible during day time as well as night
      while addressing the privacy concerns of patients. It also provides a technique
      to remotely monitor patients in a non-intrusive manner. An existing fall
      detection algorithm is currently generating fall alerts in several rooms in the
      University of Missouri Hospital (MUH). In this paper we describe a technique to
      reduce false alerts such as pillows falling off the bed or equipment movement. We
      do so by detecting the presence of the patient in the bed for the times when the
      fall alert is generated. We test our algorithm on 96 hours obtained in two
      hospital rooms from MUH. 

PMID- 25571341
TI  - The design and evaluation of an activity monitoring user interface for people
      with stroke.
AB  - Usability is an important topic in the field of telerehabilitation research.
      Older users with disabilities in particular, present age-related and disability
      related challenges that should be accommodated for in the design of a user
      interface for a telerehabilitation system. This paper describes the design,
      implementation, and assessment of a telerehabilitation system user interface that
      tries to maximize usability for an elderly user who has experienced a stroke. An
      Internet-connected Nintendo((r)) WiiTM gaming system is selected as a hardware
      platform, and a server and website are implemented to process and display the
      feedback information. The usability of the interface is assessed with a trial
      consisting of 18 subjects: 10 healthy Doctor of Physical Therapy students and 8
      people with a stroke. Results show similar levels of usability and high
      satisfaction with the gaming system interface from both groups of subjects. 

PMID- 25571342
TI  - Detecting daily routines of older adults using sensor time series clustering.
AB  - The aim of this paper is to develop an algorithm to identify deviations in
      patterns of day-to-day activities of older adults to generate alerts to the
      healthcare providers for timely interventions. Daily routines, such as bathroom
      visits, can be monitored by automated in-home sensor systems. We present a novel
      approach that finds periodicity in sensor time series data using clustering
      approach. For this study, we used data set from TigerPlace, a retirement
      community in Columbia, MO, where apartments are equipped with a network of
      motion, pressure and depth sensors. A retrospective multiple case study (N=3)
      design was used to quantify bathroom visits as parts of the older adult's daily
      routine, over a 10-day period. The distribution of duration, number, and average
      time between sensor hits was used to define the confidence level for routine
      visit extraction. Then, a hierarchical clustering was applied to extract periodic
      patterns. The performance of the proposed method was evaluated through
      experimental results. 

PMID- 25571343
TI  - Fall detection for elderly using anatomical-plane-based representation.
AB  - Falls are a common cause of injuries and traumas for elderly and could be life
      threatening. Delivering a prompt medical support after a fall is essential to
      prevent lasting injuries. Therefore, effective fall detection could provide
      urgent support and dramatically reduce the risk of such mishaps. In this paper,
      we propose a hierarchical classification framework based on a novel anatomical
      plane-based representation for elderly fall detection. The framework obtains
      human skeletal joints, using Microsoft Kinect sensors, and transforms them to a
      human representation. The representation is then utilized to classify the sensor
      input sequences and provide a semantic meaning of different human activities.
      Evaluation results of the proposed framework, using real case scenarios,
      demonstrate the efficacy of the framework in providing a feasible approach
      towards accurately detecting elderly falls. 

PMID- 25571344
TI  - Validation of the kinect for gait analysis using the GAITRite walkway.
AB  - Accurate, non-intrusive and straightforward techniques for gait quality analysis
      can provide important information concerning the fall risk of a person. For this
      purpose an algorithm was developed which can measure step length and step time
      using the Kinect depth image. The validity of the measured step length and time
      is determined using the GAITRite walkway as a ground truth. The results of this
      validation confirm that the Kinect is well-suited for determining general
      parameters of a walking sequence (a Spearmans Correlation Coefficient (SCC) of
      0.94 for average step length and 0.75 for average step time per walk), but we
      furthermore show that determining accurate results for single steps is more
      difficult (SCC of 0.74 for step length and 0.43 for step time for each step),
      making it harder to measure more complex gait parameters such as e.g. gait
      symmetry. 

PMID- 25571345
TI  - A middleware for intelligent environments in ambient assisted living.
AB  - The increasing elderly population is changing the demography of many countries,
      becoming a major issue for society. As a direct consequence of this demographic
      phenomenon, allied to technological developments and pressure to reduce
      healthcare costs, new healthcare technologies for proactive health and elder care
      is needed. However, interoperability issues among different levels of available
      technologies restricts a wider deployment among intermediate and end-users. This
      work presents a service-oriented middleware that was developed to provide access
      to the functionality offered by virtually any existing device, or application, in
      a residential setting, in a transparent and intuitive form. The proposed
      middleware abstracts the communication technologies involved, allowing to
      seemingly integrate different communication protocols, making possible the
      distributed cooperation of devices that were built as stand-alone products. As a
      test case, an application was built with the middleware to monitor blood pressure
      and electromyography signal using typical health devices. 

PMID- 25571346
TI  - A knowledge-driven approach to predicting technology adoption among Persons with
      Dementia.
AB  - As the demographics of many countries shift towards an ageing population it is
      predicted that the prevalence of diseases affecting cognitive capabilities will
      continually increase. One approach to enabling individuals with cognitive decline
      to remain in their own homes is through the use of cognitive prosthetics such as
      reminding technology. However, the benefit of such technologies is intuitively
      predicated upon their successful adoption and subsequent use. Within this paper
      we present a knowledge-based feature set which may be utilized to predict
      technology adoption amongst Persons with Dementia (PwD). The chosen feature set
      is readily obtainable during a clinical visit, is based upon real data and
      grounded in established research. We present results demonstrating 86% accuracy
      in successfully predicting adopters/non-adopters amongst PwD. 

PMID- 25571347
TI  - A sensor and video based ontology for activity recognition in smart environments.
AB  - Activity recognition is used in a wide range of applications including healthcare
      and security. In a smart environment activity recognition can be used to monitor
      and support the activities of a user. There have been a range of methods used in
      activity recognition including sensor-based approaches, vision-based approaches
      and ontological approaches. This paper presents a novel approach to activity
      recognition in a smart home environment which combines sensor and video data
      through an ontological framework. The ontology describes the relationships and
      interactions between activities, the user, objects, sensors and video data. 

PMID- 25571348
TI  - Stress-oriented driver assistance system for electric vehicles.
AB  - Stress is physiological and physical reaction that appears in highly demanding
      situations and affects human's perception and reaction capability. Occurrence of
      stress events within highly dynamic road environment could lead to life
      threatening situation. With the perspective of safety and comfort driving
      provision to anxious drivers, in this paper a stress-oriented Driver Assistance
      System (DAS) is proposed. The DAS deployed on Electric Vehicle. This novel DAS
      customizes driving command signal in respect to road context, when stress is
      detected. The effectiveness of this novel DAS is verified by simulation in
      MATLAB/SIMULINK environment. 

PMID- 25571349
TI  - An automatic fall detection framework using data fusion of Doppler radar and
      motion sensor network.
AB  - This paper describes the ongoing work of detecting falls in independent living
      senior apartments. We have developed a fall detection system with Doppler radar
      sensor and implemented ceiling radar in real senior apartments. However, the
      detection accuracy on real world data is affected by false alarms inherent in the
      real living environment, such as motions from visitors. To solve this issue, this
      paper proposes an improved framework by fusing the Doppler radar sensor result
      with a motion sensor network. As a result, performance is significantly improved
      after the data fusion by discarding the false alarms generated by visitors. The
      improvement of this new method is tested on one week of continuous data from an
      actual elderly person who frequently falls while living in her senior home. 

PMID- 25571350
TI  - A low complexity on-chip ECG data compression methodology targeting remote health
      care applications.
AB  - In this paper, we propose a novel low complexity on-chip ECG data compression
      methodology targeting remote health-care applications. This is to the best of our
      knowledge the first attempt for on-chip reliable data compression. The proposed
      methodology has been implemented targeting Application Specific Integrated
      Circuit platform at 1 MHz at Vdd 1.62 V for UMC 130 nm technology library with 16
      bits system word-length. Furthermore the proposed methodology results in a
      faithful reconstruction which has been validated using MIT-BIH PTB-DB as well as
      our institute's health repository IITH-DB. On an average about 90% compression is
      achieved with more than 83% R(2) statistics, 98% Cross Correlation and about 99%
      Regression between the original and the reconstructed data signifying the
      diagnostic accuracy. Subsequently the proposed methodology is capable of storing
      approximately 47 hrs of data in the same on-chip memory when compared to that of
      5 hours of continuous data in the state of the art which would lead to enhanced
      diagnosis and prognosis in remote health-care. 

PMID- 25571351
TI  - Integration of smartphones and webcam for the measure of spatio-temporal gait
      parameters.
AB  - A very low cost prototype has been made for the spatial and temporal analysis of
      human movement using an integrated system of last generation smartphones and a
      highdefinition webcam, controlled by a laptop. The system can be used to analyze
      mainly planar motions in non-structured environments. In this paper, the
      accelerometer signal as captured by the 3D sensor embedded in one smartphone, and
      the position of colored markers derived by the webcam frames, are used for the
      computation of spatial-temporal parameters of gait. Accuracy of results is
      compared with that obtainable by a gold-standard instrumentation. The system is
      characterized by a very low cost and by a very high level of automation. It has
      been thought to be used by non-expert users in ambulatory settings. 

PMID- 25571352
TI  - Wireless behind-the-ear EEG recording device with wireless interface to a mobile
      device (iPhone/iPod touch).
AB  - EEG remains the mainstay test for the diagnosis and treatment of patients with
      epilepsy. Unfortunately, ambulatory EEG systems are far from ideal for patients
      that have infrequent seizures. The systems only last up to 3 days and if a
      seizure is not captured during the recordings, the doctor cannot give a definite
      diagnosis of the patient's condition. The ambulatory systems also suffers from
      being too bulky and posing some constraints on the patient, such as not being
      able to shower during the recordings. This paper presents a novel behind-the-ear
      EEG recording device that uses an iPhone or iPod Touch to continuously upload the
      patient's data to a secure server. This device not only gives the doctors access
      to the EEG data in real time but it can be easily removed and re-applied by the
      patient at any time, thus reducing the interference with quality of life. 

PMID- 25571353
TI  - Antenna and coil design for wireless signal detection and charging of embedded
      power active contact lens.
AB  - This paper presents a screen printed 2.4 GHz antenna and induction charging coil
      for an active contact lens with a single large pixel user display and on-board
      3.8 V 5 uAh rechargeable battery. The antenna traces are printed using silver
      conductive paste on a 25 um polyethylene terephthalate (PET) substrate. The
      incoming signal from the antenna feeds into an IC that amplifies and rectifies
      the signal. The coil provides wireless energy transfer to inductively charge a
      thin film battery [1] located on the contact lens. The printed antenna achieved a
      S11 of -4 dB at 2.4 GHz and a gain of -13 dB. 

PMID- 25571354
TI  - A wearable wireless ultrasonic sensor network for human arm motion tracking.
AB  - This paper introduces a novel method for arm flexion/extension angles measurement
      using wireless ultrasonic sensor network. The approach uses unscented Kalman
      filter and D-H kinematical chain model to retrieve the joint angles. This method
      was experimentally validated by calculating the 2-dimensional wrist displacements
      from one mobile, placed on the point of subject's wrist, and four anchors. The
      performance of the proposed ultrasonic motion analysis system was bench-marked by
      commercial camera motion capture system. The experimental results demonstrate
      that a favorable performance of the proposed system in the estimation of upper
      limb motion. The proposed system is wireless, easy to wear, to use and much
      cheaper than current camera system. Thus, it has the potential to become a new
      and useful tool for routine clinical assessment of human motion. 

PMID- 25571355
TI  - Very long-term ECG monitoring patch with improved functionality and wearability.
AB  - Heart activity monitoring is an important task for prevention and treatment of
      cardiovascular diseases. However, development of long-term, wearable electrodes
      remains an open issue. In fact, adhesion ability and energy consumption while
      preserving aesthetics is one of the major concerns to implement a minimally
      invasive monitoring system that measures and transmits electrocardiographic
      signals (ECG) during long-term periods of time. Based on the concepts of
      functionality, wearability, and resources, we develop a new long-term ECG
      monitoring system under the wear-and-forget principle. We also propose a system
      model of the electrode-skin interface that performs real-time measurements with a
      minimally invasive effect when compared with another competitive and implantable
      systems. As a result, testing of designed prototype shows that the developed very
      long-term ECG monitoring patch improves energy consumption and adhesion time up
      to 40 days. 

PMID- 25571356
TI  - Gait as a biomarker? Accelerometers reveal that reduced movement quality while
      walking is associated with Parkinson's disease, ageing and fall risk.
AB  - Humans are living longer but morbidity has also increased; threatening to create
      a serious global burden. Our approach is to monitor gait for early warning signs
      of morbidity. Here we present highlights from a series of experiments into gait
      as a potential biomarker for Parkinson's disease (PD), ageing and fall risk.
      Using body-worn accelerometers, we developed several novel camera-less methods to
      analyze head and pelvis movements while walking. Signal processing algorithms
      were developed to extract gait parameters that represented the principal
      components of vigor, head jerk, lateral harmonic stability, and oscillation
      range. The new gait parameters were compared to accidental falls, mental state
      and co-morbidities. We observed: 1) People with PD had significantly larger and
      uncontrolled anterioposterior (AP) oscillations of the head; 2) Older people
      walked with more lateral head jerk; and, 3) the combination of vigorous and
      harmonically stable gait was demonstrated by non-fallers. Our findings agree with
      research from other groups; changes in human gait reflect changes to well-being.
      We observed; different aspects of gait reflected different functional outcomes.
      The new gait parameters therefore may be complementary to existing methods and
      may have potential as biomarkers for specific disorders. However, further
      research is required to validate our observations, and establish clinical
      utility. 

PMID- 25571357
TI  - Objective evaluation of body displacements during activities using the wearable
      inertial system ActimedARM.
AB  - This paper presents an algorithm for the objective assessment of the motion of a
      body during health-evaluation physical tests using our inertial sensor, namely
      the ActimedARM. With the orientation quaternions provided by the sensor and
      integrating twice the calibrated acceleration measurements, we are able to
      compute the displacement of the sensor worn by a patient. To validate our data we
      have made measurements with both our sensor and a reference optical system. The
      displacement curves provided by our algorithm were correlated to the gold
      standard system with a mean rate of 94.96%. 

PMID- 25571358
TI  - Multimodal flexible sensor for healthcare systems.
AB  - This paper describes potential applications of our previously developed fabric
      sensor into wearable healthcare or nursing systems based on its sensing
      modalities. This sensor is knitted from tension-sensitive electro-conductive
      yarns; whose structure has an elastic core, wound around by two separated tension
      sensitive electro-conductive threads. This makes the sensor inherently flexible
      and stretchable, allowing it to conform to any complicated surface. We have
      equipped the sensor with three modalities, including proximity that allows the
      sensor to estimate a distance from the sensor to human hand and activates a light
      touch sensing, which could initiate comfortable and friendly interfaces in order
      to reduce burden of patients/disable people during interactions with healthcare
      devices; tactile perception that can measures contact force or applied load,
      especially realize slippage acting on the sensor surface, which is promising to
      be embedded into wearable devices or smart carpets; and tensile that can quantify
      a volume's contraction/expansion, which can be employed to monitoring muscles
      activity and so on. 

PMID- 25571360
TI  - A study of position independent algorithms for phone-based gait frequency
      detection.
AB  - Estimating gait frequency is an important component in the detection and
      diagnosis of various medical conditions. Smartphone-based kinematic sensors offer
      a window of opportunity in free-living gait frequency estimation. The main issue
      with smartphone-based gait frequency estimation algorithms is how to adjust for
      variations in orientation and location of the phone on the human body. While
      numerous algorithms have been implemented to account for these differences,
      little work has been done in comparing these algorithms. In this study, we
      compare various position independent algorithms to determine which are more
      suited to robust gait frequency estimation. Using sensor data collected from
      volunteers walking with a smartphone, we examine the effect of using three
      different time series with the magnitude, weighted sum, and closest vertical
      component algorithms described in the paper. We also test two different methods
      of extracting step frequency: time domain peak counting and spectral analysis.
      The results show that the choice of time series does not significantly affect the
      accuracy of frequency measurements. Furthermore, both time domain and spectral
      approaches show comparable results. However, time domain approaches are sensitive
      to false-positives while spectral approaches require a minimum set of repetitive
      measurements. Our study suggests a hybrid approach where both time-domain and
      spectral approaches be used together to complement each other's shortcomings. 

PMID- 25571359
TI  - Miniature antenna for sensor network on human head.
AB  - This paper proposes a novel miniaturized antenna for sensor network with focus on
      placement on human head. The antenna is within the volume of 3.5*3.5*1.5 mm(3).
      It provides directive gain in the direction outward the body. 

PMID- 25571361
TI  - Bayesian-based localization of wireless capsule endoscope using received signal
      strength.
AB  - In wireless body area sensor networking (WBASN) applications such as
      gastrointestinal (GI) tract monitoring using wireless video capsule endoscopy
      (WCE), the performance of out-of-body wireless link propagating through different
      body media (i.e. blood, fat, muscle and bone) is still under investigation. Most
      of the localization algorithms are vulnerable to the variations of path-loss
      coefficient resulting in unreliable location estimation. In this paper, we
      propose a novel robust probabilistic Bayesian-based approach using received
      signal-strength (RSS) measurements that accounts for Rayleigh fading, variable
      path-loss exponent and uncertainty in location information received from the
      neighboring nodes and anchors. The results of this study showed that the
      localization root mean square error of our Bayesian-based method was 1.6 mm which
      was very close to the optimum Cramer-Rao lower bound (CRLB) and significantly
      smaller than that of other existing localization approaches (i.e. classical MDS
      (64.2mm), dwMDS (32.2mm), MLE (36.3mm) and POCS (2.3mm)). 

PMID- 25571362
TI  - Multiple subject analysis of functional brain network communities through co
      regularized spectral clustering.
AB  - In recent years, the human brain has been characterized as a complex network
      composed of segregated modules linked by short path lengths. In order to
      understand the organization of the network, it is important to determine these
      modules underlying the functional brain networks. However, the study of these
      modules is confounded by the fact that most neurophysiological studies consist of
      data collected from multiple subjects. Typically, this problem is addressed by
      either averaging the data across subjects which omits the variability across
      subjects or using consensus clustering methods which treats all subjects equally
      irrespective of outliers in the data. In this paper, we adapt a recently
      introduced co-regularized multiview spectral clustering approach to address these
      problems. The proposed framework is applied to EEG data collected during a study
      of error-related negativity (ERN) to better understand the functional networks
      involved in cognitive control and to compare between the network structure
      between error and correct responses. 

PMID- 25571363
TI  - A supervised multi-sensor matched filter for the detection of extracellular
      action potentials.
AB  - Multi-sensor extracellular recording takes advantage of several electrode
      channels to record from multiple neurons at the same time. However, the resulting
      low signal-to-noise ratio (SNR) combined with biological noise makes signal
      detection, the first step of any neurophysiological data analysis, difficult. A
      matched filter was therefore designed to better detect extracellular action
      potentials (EAPs) from multi-sensor extracellular recordings. The detector was
      tested on tetrode data from a locust antennal lobe and assessed against three
      trained analysts. 25 EAPs and noise samples were selected manually from the data
      and used for training. To reduce complexity, the filter assumed that the
      underlying noise in the data was spatially white. The detector performed with an
      average TP and FP rate of 84.62% and 16.63% respectively. This high level of
      performance indicates the algorithm is suitable for widespread use. 

PMID- 25571364
TI  - A low-power, time-division-multiplexed vector matrix-multiplier for a vestibular
      prosthesis.
AB  - A custom analog vector matrix multiplier (VMM) for a vestibular prosthesis is
      reported. The VMM functions to reduce misalignment between implanted angular rate
      sensors and associated peripheral sense organs and precompensate for spurious
      electrical stimulation of vestibular neurons. Operating in the CMOS subthreshold
      region, the VMM performs a 3-by-3 vector matrix multiplication of rate sensor
      outputs, magnitude <; +/-250 mV, and bandwidth <; 1.25 kHz. To reduce
      susceptibility to device mismatches, time-division-multiplexed multiplication is
      employed requiring 727 MUs for a complete operation cycle. Fabricated with TSMC
      0.35 MUm CMOS technology, the footprint is 1523 MUm * 1548 MUm and consumes 5.37
      MUW of power. 

PMID- 25571365
TI  - A graph theoretic approach to dynamic functional connectivity tracking and
      network state identification.
AB  - With the advances in neuroimaging technology, it is now possible to measure human
      brain activity with increasing temporal and spatial resolution. This vast amount
      of spatio-temporal data requires the development of computational methods capable
      of building an integrated picture of the functional networks for a better
      understanding of the healthy and diseased brain [1]. Although the construction of
      these networks from neuroimaging data is well-established [2], current approaches
      are limited to the characterization of the global topology of static networks
      where the links between different brain regions represent average connectivity
      over a long time period [3], [2]. Recent studies suggest that human cognition
      arises from the rapid formation and dissociation of synchronized neural activity
      on short time scales in the order of milliseconds [4]. There is a strong need for
      new electroencephalogram (EEG)-based analytic frameworks for monitoring dynamic
      functional network activity. In this paper, we propose a graph theoretic approach
      for tracking the changing topology of functional connectivity networks across
      time. First, we introduce an event detection algorithm based on node level
      feature extraction and principal components analysis of time-dependent node
      correlation matrices. Then, we propose a k-means based clustering approach to
      characterize each time interval with the most common connectivity states.
      Finally, the proposed methodology is applied to the study of the dynamics of
      functional connectivity networks during error-related negativity (ERN). 

PMID- 25571366
TI  - Directionality in cardiovascular variability interactions during head-down tilt
      test.
AB  - A nonlinear model-free Granger causality approach was exploited to quantify the
      strength of the causal relation along cardiac baroreflex and cardiopulmonary
      pathway from spontaneous cardiovascular variabilities during head-down tilt
      (HDT). The analysis was completed through the assessment of traditional time and
      frequency domain parameters and cardiac baroreflex sensitivity. We found that,
      while respiratory sinus arrhythmia augmented, the power of the systolic arterial
      pressure variability in the low frequency band (i.e. from 0.04 to 0.15 Hz)
      decreased and cardiac baroreflex sensitivity increased, the strength of the
      causal relation along cardiac baroreflex and cardiopulmonary pathway remained
      constant. We conclude that, despite cardiopulmonary stimulation and sympathetic
      inhibition induced by HDT, neither cardiac baroreflex nor cardiopulmonary pathway
      took prevalence in governing heart period changes during HDT. 

PMID- 25571367
TI  - Three-dimensional segmented poincare plot analysis - A new approach of
      cardiovascular and cardiorespiratory regulation analysis.
AB  - Hypertensive pregnancy disorders affect 6 to 8 percent of all pregnancies which
      can cause severe complications for the mother and the fetus. The aim of this
      study was to develop a new method suitable for a three dimensional coupling
      analysis. Therefore, the three-dimensional segmented Poincare plot analysis
      (SPPA3) is introduced that represents the Poincare analysis based on a cubic box
      model representation. The box representing the three dimensional phase space is
      (based on the SPPA method) subdivided into 12*12*12 equal cubelets according to
      the predefined range of signals and all single probabilities of occurring points
      in a specific cubelet related to the total number of points are calculated. From
      10 healthy non-pregnant women, 66 healthy pregnant women and 56 hypertensive
      pregnant women suffering from chronic hypertension, gestational hypertension and
      preeclampsia, 30 minutes of beat-to-beat intervals (BBI), noninvasive blood
      pressure and respiration (RESP) were continuously recorded and analyzed.
      Couplings between the different signals were analyzed. The ability of SPPA3 for a
      screening could be confirmed by multivariate discriminant analysis
      differentiating between all pregnant woman and preeclampsia (index
      BBI3_SBP9_RESP6/ BBI8_SBP11_RESP4 leads to an area under the ROC curve of
      AUC=91.2%). In conclusion, SPPA3 could be a useful method for enhanced risk
      stratification in pregnant women. 

PMID- 25571368
TI  - Symbolic dynamics of respiratory cycle related sleep EEG in children with sleep
      disordered breathing.
AB  - Childhood sleep disordered breathing (SDB) is characterized by an increased work
      of breathing, restless night sleep and excessive daytime sleepiness and has been
      associated with cognitive impairment, behavioral disturbances and early
      cardiovascular changes. Compared to normal controls, children with SDB have
      elevated arousal thresholds and their sleep EEG may elicit cortical activation
      associated with arousals but often too subtle to be visually scored. The aim of
      this study was to assess EEG complexity throughout the respiratory cycle based on
      symbolic dynamics in children with SDB (n=40) and matched healthy controls. EEG
      amplitude values were symbolized based on the quartiles of their distribution and
      words of length 3 were formed and classed into 4 types based on their patterns.
      Children with SDB showed less complex EEG dynamics in non-REM sleep that was
      unrelated to the respiratory phase. In REM sleep normal children showed a
      respiratory phase-related reduction in EEG variability during the expiratory
      phase compared to inspiration, which was not apparent in children with SDB. In
      conclusion, respiratory cycle related EEG dynamics are altered in children with
      SDB during REM sleep and indicate changes in cortical activity. 

PMID- 25571369
TI  - Investigating cardiac and respiratory determinants of heart rate variability in
      an information-theoretic framework.
AB  - This study was aimed at comparing two alternative information-theoretic
      approaches for the combined analysis of heart rate variability (HRV) and
      respiration variability (RV). The approaches decompose the predictive information
      about HRV in two terms, quantifying respectively the information stored into HRV
      and that transferred to HRV from RV. Storage and transfer were assessed by the
      popular self entropy (SE) and transfer entropy (TE) measures, as well as by the
      alternative conditional SE (cSE) and cross entropy (CE) measures. The comparison
      was performed at a theoretical level, computing the exact values of the four
      measures for simulated cardiorespiratory dynamics, and on real data, estimating
      the measures from RV and HRV time series taken from healthy subjects during head
      up tilt and paced breathing protocols. Both analyses suggested that, for the
      study of cardiorespiratory interactions which are mostly unidirectional from RV
      to HRV, the decomposition evidencing cSE and CE is more suitable to describe
      respiratory sinus arrhythmia and its modifications related to changes in
      cardiorespiratory interactions. 

PMID- 25571370
TI  - Assessing the convolutedness of multivariate physiological time series.
AB  - A feature of time-series variability that may reveal underlying complex dynamics
      is the degree of "convolutedness". For multivariate series of m components,
      convolutedness can be defined as the propensity of the trail of the time-series
      samples to fill the m-dimensional space. This work proposes different
      convolutedness indices and compare them on synthesized and real physiological
      signals. The indices are based on length L and planar extension d of the trail in
      m dimensions. The classical ones are: the L/d ratio, and the Mandelbrot's fractal
      dimension (FD) of a curve: FDM =log(L)/log(d). In this work we also consider a
      correction of the Katz's estimator of FDM, i.e., FDKC =log(N)/(log(N)+log(d/L)),
      with N the number of samples; and FDMC, an estimator of FDM based on FDKC
      calculated over a shorter running window Nw<;N appropriately selected to reduce
      estimation bias. Synthesized fractional Brownian motions indicated that all the
      indices increase with FD, but differ for other aspects, namely the dependence on
      N; the capacity to estimate FD; or to distinguish between true bivariate and
      degenerate bivariate time series. Application on real multivariate recordings of
      muscular activity before and after exercise-induced fatigue suggests that these
      indices can be profitably used to identify complex changes in the dynamics of
      physiological signals. 

PMID- 25571371
TI  - Multivariate nonstationary modeling of cerebral hemodynamics.
AB  - We extracted adaptive univariate and multivariate dynamic models of cerebral
      hemodynamics during resting and hypercapnic conditions using a Recursive Least
      Squares estimation scheme with multiple adaptive forgetting factors. The time
      dependent relationship between mean arterial blood pressure (MABP), end-tidal CO2
      tension (PETCO2) and middle cerebral artery blood flow velocity (CBFV) was
      assessed using Laguerre - Volterra models with time varying coefficients. The
      results suggest that the addition of PETCO2 as a second input yields more
      accurate and less nonstationary estimates, indicating that unobservable
      physiological variables are important in the context of nonstationary systems
      modeling, and particularly for assessing cerebral hemodynamics and
      autoregulation. 

PMID- 25571372
TI  - Near-optimal keypoint sampling for fast pathological lung segmentation.
AB  - Accurate delineation of pathological lungs from computed tomography (CT) images
      remains mostly unsolved because available methods fail to provide a reliable
      generic solution due to high variability of abnormality appearance. Local
      descriptor-based classification methods have shown to work well in annotating
      pathologies; however, these methods are usually computationally intensive which
      restricts their widespread use in real-time or near-real-time clinical
      applications. In this paper, we present a novel approach for fast, accurate,
      reliable segmentation of pathological lungs from CT scans by combining region
      based segmentation method with local-descriptor classification that is performed
      on an optimized sampling grid. Our method works in two stages; during stage one,
      we adapted the fuzzy connectedness (FC) image segmentation algorithm to perform
      initial lung parenchyma extraction. In the second stage, texture-based local
      descriptors are utilized to segment abnormal imaging patterns using a near
      optimal keypoint analysis by employing centroid of supervoxel as grid points. The
      quantitative results show that our pathological lung segmentation method is fast,
      robust, and improves on current standards and has potential to enhance the
      performance of routine clinical tasks. 

PMID- 25571373
TI  - Accurate and efficient separation of left and right lungs from 3D CT scans: A
      generic hysteresis approach.
AB  - Separation of left and right lungs from binary segmentation is often necessary
      for quantitative image-based pulmonary disease evaluation. In this article, we
      present a new fully automated approach for accurate, robust, and efficient lung
      separation using 3-D CT scans. Our method follows a hysteresis setting that
      utilizes information from both lung regions and background gaps. First, original
      segmentation is separated by subtracting the gaps between left and right lungs,
      which are enhanced with Hessian filtering. Second, the 2-D separation manifold in
      3-D image space is estimated based on the distance information from the two
      subsets. Finally, the separation manifold is projected back to the original
      segmentation in order to produce the separated lungs through optimization for
      addressing minor local variations. An evaluation on over 400 human and 100 small
      animal 3-D CT images with various abnormalities is performed. The proposed scheme
      successfully separated all connections on the candidate CT images. Using
      hysteresis mechanism, each phase is performed robustly and 3-D information is
      utilized to achieve a generic, efficient, and accurate solution. 

PMID- 25571374
TI  - Classification of interstitial lung disease patterns using local DCT features and
      random forest.
AB  - Over the last decade, a plethora of computer-aided diagnosis (CAD) systems have
      been proposed aiming to improve the accuracy of the physicians in the diagnosis
      of interstitial lung diseases (ILD). In this study, we propose a scheme for the
      classification of HRCT image patches with ILD abnormalities as a basic component
      towards the quantification of the various ILD patterns in the lung. The feature
      extraction method relies on local spectral analysis using a DCT-based filter
      bank. After convolving the image with the filter bank, q-quantiles are computed
      for describing the distribution of local frequencies that characterize image
      texture. Then, the gray-level histogram values of the original image are added
      forming the final feature vector. The classification of the already described
      patches is done by a random forest (RF) classifier. The experimental results
      prove the superior performance and efficiency of the proposed approach compared
      against the state-of-the-art. 

PMID- 25571375
TI  - Repeat validation of a method to measure in vivo three dimensional hip kinematics
      using computed tomography and fluoroscopy.
AB  - Total hip arthroplasty or THA is a surgical procedure for the relief of
      significant disabling pain caused by osteoarthritis or hip fracture. Knowledge of
      the 3D kinematics of the hip during specific functional activities is important
      for THA component design. In this paper we compare kinematic measurements
      obtained by a new 2D-3D registration algorithm with measurements provided by the
      gold standard roentgen stereo analysis (RSA). The study validates a promising
      method for investigating the kinematics of some pathologies, which involves
      fitting three dimensional patient specific 3D CT scans to dynamic fluoroscopic
      images of the hip during functional activities. This is the first study in which
      single plane fluoroscopy has been used for kinematic measurements of natural hip
      bones. The main focus of the study is on the out-of-plane translation and
      rotation movements which are difficult to measure precisely using a single plane
      approach. From our experimental results we found that the precision of our
      proposed approach compares favourably with that of the most recent dual plane
      fluoroscopy approach. 

PMID- 25571376
TI  - Computational assessment of stereoscopic viewing a sequence of stereo pairs of
      breast tomosynthesis projection images.
AB  - Digital breast tomosynthesis (DBT) is a 3D imaging technology in which an x-ray
      fan beam rotates around the breast, producing a series of projection images. The
      imaging geometry of DBT lends itself naturally to stereo viewing because a stereo
      pair can be easily formed by two projection images with a reasonable separation
      angle. Stereo viewing may reveal the 3D structures of breasts thus has the
      potential to increase the sensitivity and specificity of breast imaging. In this
      study, we conduct a simulation study that mimics the detection of breast lesions
      on stereoscopic viewing of DBT projections. The presentation approach we
      investigate here is one in which the reader is presented with a sequence of
      stereo pairs from a rotating point of view. We render voxel datasets that contain
      random 3D power-law noise to model normal breast tissues with different breast
      densities. A 3D Gaussian signal is inserted to some of the datasets to model the
      presence of a breast lesion. Sequences of stereo pairs of projection images are
      generated for each voxel dataset by varying the projection angles of the two
      views. The diagnostic performance, in terms of the accuracy of binary decisions
      on the presence of the simulated lesions, is evaluated with a numerical model
      observer. 

PMID- 25571377
TI  - 3D digital breast tomosynthesis image reconstruction using anisotropic total
      variation minimization.
AB  - This paper presents a compressed sensing based reconstruction method for 3D
      digital breast tomosynthesis (DBT) imaging. Algebraic reconstruction technique
      (ART) has been in use in DBT imaging by minimizing the isotropic total variation
      (TV) of the reconstructed image. The resolution in DBT differs in sagittal and
      axial directions which should be encountered during the TV minimization. In this
      study we develop a 3D anisotropic TV (ATV) minimization by considering the
      different resolutions in different directions. A customized 3D Shepp-logan
      phantom was generated to mimic a real DBT image by considering the overlapping
      tissue and directional resolution issues. Results of the ART, ART+3D TV and
      ART+3D ATV are compared using structural similarity (SSIM) diagram. 

PMID- 25571378
TI  - Gradient-based magnetic resonance electrical properties imaging of brain tissues.
AB  - Electrical properties tomography (EPT) holds promise for noninvasively mapping at
      high spatial resolution the electrical conductivity and permittivity of
      biological tissues in vivo using a magnetic resonance imaging (MRI) scanner. In
      the present study, we have developed a novel gradient-based EPT approach with
      greatly improved tissue boundary reconstruction and largely elevated robustness
      against measurement noise compared to existing techniques. Using a 7 Tesla MRI
      system, we report, for the first time, high-quality in vivo human brain
      electrical property images with refined structural details, which can potentially
      merit clinical diagnosis (such as cancer detection) and high-field MRI
      applications (quantification of local specific absorption rate) in the future. 

PMID- 25571379
TI  - 2D Magnetic resonance electrical property tomography based on B1(-) field
      mapping.
AB  - Magnetic Resonance Electrical Property Tomography (MREPT) is a method to
      visualize electrical conductivity and permittivity distributions in the object.
      Traditional MREPT relies on either the radio frequency (RF) transmit field
      (B(+)1) mapping, or using a transmit/receive RF coil, to compute tissue's
      electrical conductivity and permittivity. This paper introduces an alternative
      approach based on the reconstructed receive field (B(-)1) By solving a system of
      homogeneous equations consisting of the signal ratios from multi-channel receive
      coils, the receive field distribution with both magnitude and phase can be
      computed. Similar to (B(+)1) based MREPT method, the conductivity and
      permittivity in the imaging object can be calculated from the (B(-)1) field. We
      demonstrated the feasibility to image electrical property contrasts through
      computer simulated studies and phantom experiments. Although this study focuses
      on the 2D reconstruction, the presented method can be extended to full 3D. This
      method can be applied to regular MR imaging collected with multi-channel receive
      coils, and therefore, tissue anomaly based on electrical properties can
      potentially be revealed with a higher imaging quality, providing useful
      information for clinical diagnosis. 

PMID- 25571380
TI  - Real-time 3D electrical impedance imaging for ventilation monitoring of the lung:
      Pilot study.
AB  - We report an Electrical Impedance Tomography device capable of detecting gravity
      induced regional ventilation changes in real-time without averaging or using a
      contrast medium. Changes in lung ventilation are demonstrated in right and left
      lateral decubitus position and compared to those seen in an upright and supine
      normal subject. 

PMID- 25571381
TI  - Electrical impedance tomography for assessing ventilation/perfusion mismatch for
      pulmonary embolism detection without interruptions in respiration.
AB  - Recent studies have shown high correlation between pulmonary perfusion mapping
      with impedance contrast enhanced Electrical Impedance Tomography (EIT) and
      standard perfusion imaging methods such as Computed Tomography (CT) and Single
      Photon Emission Computerized Tomography (SPECT). EIT has many advantages over
      standard imaging methods as it is highly portable and non-invasive. Contrast
      enhanced EIT uses hypertonic saline bolus instead of nephrotoxic contrast medium
      that are utilized by CT and nuclear Ventilation/Perfusion (V/Q) scans. However,
      current implementation of contrast enhanced EIT requires induction of an apnea
      period for perfusion measurement, rendering it disadvantageous compared with
      current gold standard imaging modalities. In the present paper, we propose the
      use of a wavelet denoising algorithm to separate perfusion signal from
      ventilation signal such that no interruption in patient's ventilation would be
      required. Furthermore, right lung to left lung perfusion ratio and ventilation
      ratio are proposed to assess the mismatch between ventilation and perfusion for
      detection of Pulmonary Embolism (PE). The proposed methodology was validated on
      an ovine model (n=3, 83.7+/-7.7 kg) with artificially induced PE in the right
      lung. The results showed a difference in right lung to left lung perfusion ratio
      between baseline and diseased states in all cases with all paired t-tests between
      baseline and PE yielding p <; 0.01, while the right lung to left lung ventilation
      ratio remained unchanged in two out of three experiments. Statistics were pooled
      from multiple repetitions of measurements per experiment. 

PMID- 25571382
TI  - Harmonic Motion Microwave Doppler Imaging method for breast tumor detection.
AB  - Harmonic Motion Microwave Doppler Imaging (HMMDI) method is recently proposed as
      a non-invasive hybrid breast imaging technique for tumor detection. The acquired
      data depend on acoustic, elastic and electromagnetic properties of the tissue.
      The potential of the method is analyzed with simulation studies and phantom
      experiments. In this paper, the results of these studies are summarized. It is
      shown that HMMDI method has a potential to detect malignancies inside fibro
      glandular tissue. 

PMID- 25571383
TI  - Modular architecture of a multi-frequency electrical impedance tomography system:
      design and implementation.
AB  - Electrical impedance tomography (EIT) provides means of imaging the electrical
      properties distribution of biological tissues and fluids while impedance
      spectroscopy (IS) allows measuring their frequency response in a more global way.
      Both require precise and well-integrated instrumentation. In this work, we
      propose a modular architecture of a multi-frequency EIT (MfEIT) system which has
      capabilities in implementing both IS and MfEIT. First, IS performance is assessed
      in vivo using a cuff electrode implanted around the rodent cervical vagus nerve.
      Second, MfEIT performance is evaluated in vitro based on saline phantom
      experiments. Overall system allows addressing a wide range of applications and
      proves effective both in vitro and in vivo. 

PMID- 25571384
TI  - Seismocardiography-based detection of cardiac quiescence for cardiac computed
      tomography angiography.
AB  - As a measure of chest wall acceleration caused by cardiac motion, the
      seismocardiogram (SCG) has the potential to supplement the electrocardiogram
      (ECG) to more accurately trigger cardiac computed tomography angiography (CTA)
      data acquisition during periods of cardiac quiescence. The SCG was used to
      identify the systolic and diastolic quiescent periods of the cardiac cycle on a
      beat-by-beat basis and from composite velocity signals for nine healthy subjects.
      The cardiac velocity transmitted to the chest wall was calculated using a Kalman
      filter. The average systolic and diastolic quiescent periods were centered at 30%
      and 76%, respectively. Inter- and intra-subject variability of the quiescent
      phases with respect to the ECG was observed, suggesting that the ECG may be a
      suboptimal modality for predicting cardiac quiescence. 

PMID- 25571385
TI  - Three dimensional Ballistocardiogram and Seismocardiogram: what do they have in
      common?
AB  - 3D-body accelerations, i.e. Ballistocardiograms (BCG) and Seismocardiograms
      (SCG), ECG and Impedance-cardiograms (ICG) were recorded on healthy volunteers
      participating to the European Space Agency (ESA) 59th parabolic flight campaign.
      In the present paper we document the similarities and differences that can be
      seen in the seismo- and ballisto-cardiogram signals in different positions
      (standing and supine) under normal gravity condition as well as during the
      weightlessness phases (0G) of a parabolic flight. Our results demonstrate that
      SCG and BCG both present a similar three dimensional (3D) nature, with components
      of the BCG having lower frequency content than the SCG. The recordings performed
      in the 0G environment are the one with the smoothest shape and largest maximum
      magnitude of the Force vector. The differences seen between SCG and BCG stress
      further the importance for the need of using different nomenclature for the
      identification of peaks in both signals.

PMID- 25571386
TI  - Wearable seismocardiography for the beat-to-beat assessment of cardiac intervals
      during sleep.
AB  - Seismocardiogram (SCG) can be detected during sleep by a textile-based wearable
      system. This pilot study preliminarily explores the feasibility of a beat-to-beat
      estimation of cardiac mechanical features (RR interval, RRI, Pre-Ejection Period,
      PEP, Isovolumic Contraction Time, ICT, Left Ventricular Ejection Time, LVET,
      Isovolumic Relaxation Time, IRT) from the joint ECG and SCG assessment during
      sleep. The analysis of two 30-min sleep data segments from one healthy subject,
      indicated that 1) respiration largely influence the dynamics of most of the
      parameters; 2) variability of cardiac intervals is only marginally influenced by
      the RRI variability; 3) appreciable spectral power at frequencies <= 0.1 is only
      observed in the RRI spectrum and not in the spectra of the other indexes; 4) IRT
      has a broadband variability, that is clearly different from the dynamics of the
      other indexes. These findings represent the very first description of the beat-to
      beat variability of cardiac mechanical indexes. Further investigations on a
      larger population are in progress to confirm the present results.

PMID- 25571387
TI  - Preliminary results on quantification of Seismocardiogram morphological changes,
      using principal component analysis.
AB  - A methodology, based on principal component analysis, is proposed to quantify
      beat to beat Seismocardiogram changes. The proposed method was tested over a
      population of 94 subjects including 35 ischemic heart disease patients. The
      results showed that there was an insignificant overlap between the diseased and
      the healthy populations in the number of principal components (NPC) and that
      further development of this method might yield a classification index for
      myocardial abnormalities. In addition such an index has potential utility in
      patient monitoring. 

PMID- 25571388
TI  - The unique characteristics of ON and OFF retinal ganglion cells: a modeling
      study.
AB  - Retinal ganglion cells (RGCs) demonstrate a large range of variation in their
      ionic channel properties and morphologies. These cell-specific properties are
      responsible for the unique way they process synaptic inputs. A cell-specific
      modeling approach allows us to examine the functional significance of regional
      membrane channel expression and cell morphology. ON and OFF RGC models based on
      accurate biophysics and realistic representation of morphologies were used to
      study the contribution of different ion channel properties and spatial structure
      of neurons to RGC electrical activity. Using this approach, morphologically
      complex retinal neurons such as amacrine cells or RGCs can be modelled and their
      interactions and processing can be better understood. 

PMID- 25571390
TI  - On the analysis of using 3-coil wireless power transfer system in retinal
      prosthesis.
AB  - Designing a wireless power transmission system(WPTS) using inductive coupling has
      been investigated extensively in the last decade. Depending on the different
      configurations of the coupling system, there have been various designing methods
      to optimise the power transmission efficiency based on the tuning circuitry,
      quality factor optimisation and geometrical configuration. Recently, a 3-coil
      WPTS was introduced in retinal prosthesis to overcome the low power transferring
      efficiency due to low coupling coefficient. Here we present a method to analyse
      this 3-coil WPTS using the S-parameters to directly obtain maximum achievable
      power transferring efficiency. Through electromagnetic simulation, we brought a
      question on the condition of improvement using 3-coil WPTS in powering retinal
      prosthesis. 

PMID- 25571389
TI  - A multi-scale computational model for the study of retinal prosthetic
      stimulation.
AB  - An implantable retinal prosthesis has been developed to restore vision to
      patients who have been blinded by degenerative diseases that destroy
      photoreceptors. By electrically stimulating the surviving retinal cells, the
      damaged photoreceptors may be bypassed and limited vision can be restored. While
      this has been shown to restore partial vision, the understanding of how cells
      react to this systematic electrical stimulation is largely unknown. Better
      predictive models and a deeper understanding of neural responses to electrical
      stimulation is necessary for designing a successful prosthesis. In this work, a
      computational model of an epi-retinal implant was built and simulated, spanning
      multiple spatial scales, including a large-scale model of the retina and implant
      electronics, as well as underlying neuronal networks. 

PMID- 25571391
TI  - Selective activation of ON and OFF retinal ganglion cells to high-frequency
      electrical stimulation: a computational modeling study.
AB  - In this study, ON and OFF retinal ganglion cell (RGC) models based on accurate
      biophysics and realistic representations of cell morphologies were used to
      understand how these cells selectively respond to high-frequency electrical
      stimulation (HFS). With optimized model parameters and the incorporation of
      detailed cell morphologies, these two models were able to closely replicate
      experimental ON and OFF RGC responses to epiretinal electrical stimulation. This
      modeling approach can be used to design electrical stimulus profiles capable of
      cell-specific activation, and is broadly applicable for the development of
      sophisticated stimulation strategies for visual prostheses. 

PMID- 25571392
TI  - Benefit of spatial filtering for visual perception with a subretinal implant.
AB  - Subretinal implants have proven to be capable of restoring vision to patients
      suffering from hereditary retinal degeneration diseases like retinitis pigmentosa
      and cone-rod dystrophy. Although they already provide basic visual perception,
      there is still much room for improvement in this field. Effects like electric
      field interference limit the visual acuity and may be the cause of the perceived
      vision to be blurred. This influence could be reduced by means of highpass
      spatial filtering. In this paper, based on the available reports about the visual
      perception parameters from the patients using the alpha-IMS subretinal implant, a
      model for the blurring effect of the patients retina is proposed. On this basis,
      highpass filters are suggested which will compensate the obscuring effect of the
      stimulator device plus retina system to some extent. 

PMID- 25571393
TI  - Reproducing retinal rod bipolar cell light response by mathematical model
      including neurotransmitter receptors.
AB  - Detailed mathematical model of retinal cells is useful for the quantitative
      understanding of the subcellular processes of the visual system. Retinal bipolar
      cells receive information from photoreceptor cells, horizontal cells and amacrine
      cells, thus it can be considered as information integration system. Despite its
      importance, bipolar cell model including inputs and outputs has not been
      proposed. In this paper, we propose a rod bipolar cell model which can reproduce
      voltage response of light. The model includes TRPM1 channel which receives signal
      from photoreceptor cells, GABA channel which receives signal from surrounding
      amacrine cells, and cell body model which is based on the model proposed by
      Ishihara et al. The model was evaluated with several light signals, where
      experimentally obtained photoreceptor cell responses were used as TRPM1 channel
      input. Resulting bipolar cell membrane potential showed good agreement with the
      reported experimental results. 

PMID- 25571394
TI  - A body machine interface based on inertial sensors.
AB  - Spinal cord injury (SCI) survivors generally retain residual motor and sensory
      functions, which provide them with the means to control assistive devices. A body
      machine interface (BoMI) establishes a mapping from these residual body movements
      to control commands for an external device. In this study, we designed a BoMI to
      smooth the way for operating computers, powered wheelchairs and other assistive
      technologies after cervical spinal cord injuries. The interface design included a
      comprehensive training paradigm with a range of diverse functional activities to
      enhance motor learning and retention. Two groups of SCI survivors and healthy
      control subjects participated in the study. The results indicate the
      effectiveness of the developed system as an alternative pathway for individuals
      with motor disabilities to control assistive devices while engaging in functional
      motor activity. 

PMID- 25571395
TI  - The response of L5 pyramidal neurons of the PFC to magnetic stimulation from a
      micro-coil.
AB  - Magnetic stimulation of the nervous system, e.g. transcranial magnetic
      stimulation (TMS), has been used both to unravel basic structure and function of
      the nervous system as well as to treat neurological diseases, i.e. clinical
      depression. Despite progress in both areas, ongoing advancements have been
      limited by a lack of understanding of the mechanism by which magnetic stimulation
      alters neural activity. Here, we report responses of cortical neurons to magnetic
      stimulation arising from a sub-millimeter coil. Cell attached patch clamp was
      used to record neural activity of layer 5/6 pyramidal neurons of the prefrontal
      cortex (PFC) in the in vitro mouse brain slice preparation. The fields arising
      from the small coil were quite different from those arising during clinical TMS
      but nevertheless allowed the responses of cortical neurons to magnetic
      stimulation to be probed. For example, the focal nature of induced fields allowed
      the sensitivity of different regions within targeted pyramidal neurons, e.g.
      apical dendrite, soma and axon hillock, to be compared. We found that PFC
      pyramidal neurons were not sensitive to single pulses of stimulation regardless
      of coil location. However, regions of the apical dendrite and proximal axon were
      both sensitive to repetitive stimulation as long as the orientation of the
      induced electric field was aligned with the long axis of the neuron. These
      results suggest that neurons of the PFC are sensitive to weak magnetic fields and
      further, that this type of approach may be useful for unraveling some of the
      mechanisms underlying TMS. 

PMID- 25571396
TI  - Approximating transcranial magnetic stimulation with electric stimulation in
      mouse: a simulation study.
AB  - Rodent models are valuable for preclinical examination of novel therapeutic
      techniques, including transcranial magnetic stimulation (TMS). However,
      comparison of TMS effects in rodents and humans is confounded by inaccurate
      scaling of the spatial extent of the induced electric field in rodents. The
      electric field is substantially less focal in rodent models of TMS due to the
      technical restrictions of making very small coils that can handle the currents
      required for TMS. We examine the electric field distributions generated by
      various electrode configurations of electric stimulation in an inhomogeneous high
      resolution finite element mouse model, and show that the electric field
      distributions produced by human TMS can be approximated by electric stimulation
      in mouse. Based on these results and the limits of magnetic stimulation in mice,
      we argue that the most practical and accurate way to model focal TMS in mice is
      electric stimulation through either cortical surface electrodes or electrodes
      implanted halfway through the mouse cranium. This approach could allow much more
      accurate approximation of the human TMS electric field focality and strength than
      that offered by TMS in mouse, enabling, for example, focal targeting of specific
      cortical regions, which is common in human TMS paradigms. 

PMID- 25571397
TI  - A 1024-channel 6 mW/mm2 optical stimulator for in-vitro neuroscience experiments.
AB  - Recent optical stimulation technologies allow improved selectivity and have been
      widely used in neuroscience research. This paper presents an optical stimulator
      based on high power LEDs. It has 1024 channels and can produce flexible
      stimulation patterns in each frame, refreshed at above 20 Hz. To increase the
      light intensity, each LED has an optical package that directs the light into a
      small angle. To ensure the light of each LED can reach the lens, the LEDs have
      been specially placed and oriented to the lens. With these efforts, the achieved
      power efficiency (defined as the mount of LED light power passing through the
      lens divided by the LED total power consumption) is 5 * 10(-5). In our current
      prototype, an individual LED unit can source 60 mW electrical power, where the
      induced irradiance on neural tissues is 6 mW/mm(2) integrating from 460 nm to 480
      nm. The light spot is tunable in size from 18 MUm to 40 MUm with an extra 5-10
      MUm separation for isolating two adjacent spots. Through both bench-top
      measurement and finite element simulation, we found the cross channel
      interference is below 10%. A customized software interface has been developed to
      control and program the stimulator operation.

PMID- 25571398
TI  - Chronic transcranial focal stimulation from tripolar concentric ring electrodes
      does not disrupt memory formation in rats.
AB  - Non-invasive electrical brain stimulation has shown potential utility as a
      treatment for seizures in epilepsy patients. Transcranial focal stimulation (TFS)
      via tripolar concentric ring electrodes (TCREs) has been effective in reducing
      seizure severity in acute rodent models, but it has yet to be determined whether
      or not it will serve as a viable long-term treatment strategy. Prior experiments
      indicate that a single dose of TFS via TCRE does not impact short- or long-term
      memory formation. The present study investigated if five daily doses of TFS via a
      TCRE on the scalp affected the memory. The spontaneous object recognition (SOR)
      test was used to evaluate the memory. Sham and TFS-treated groups were evaluated
      and both showed comparable levels of preference for novel objects, indicating
      successful memory formation. More work on repeated dosage strategies is important
      for establishing the safety and efficacy of TFS as a putative treatment. 

PMID- 25571399
TI  - Optical stimulation of primary motor cortex with 980nm infrared neural
      stimulation.
AB  - To explore the penetration depth with short-wavelength infrared light, 980 nm
      pulse infrared light was used to stimulate the primary motor cortex of rat. The
      heating model was created to simulate the temperature distribution for 1875 nm
      and 980 nm infrared neural stimulation. Post-stimulus time histogram was used to
      observe the neural response induced by Infrared neural stimulation on primary
      motor cortex. The model predicted the penetration depth of 980 nm was deep into
      1.2 mm. Cortical neural located between 500 MUm to 1000 MUm were successfully
      activated by 980 nm INS. The preliminary results suggested that, 980 nm pulse INS
      could serve as a candidate for deep tissue stimulation.

PMID- 25571400
TI  - A new paradigm for treatment of glaucoma.
AB  - Glaucoma is the leading irreversible cause of blindness in the world. We are
      developing a new image-guidance system to deliver a neuroprotective drug in a
      controlled release nanosponge. The system consists of a magnetically tracked
      image-guidance system, the nanosponge material and the drug. We have
      characterized the performance of each aspect in phantoms, animals and ex-vivo
      human tissue. 

PMID- 25571401
TI  - 3D ultrasound imaging in image-guided intervention.
AB  - Ultrasound imaging is used extensively in diagnosis and image-guidance for
      interventions of human diseases. However, conventional 2D ultrasound suffers from
      limitations since it can only provide 2D images of 3-dimensional structures in
      the body. Thus, measurement of organ size is variable, and guidance of
      interventions is limited, as the physician is required to mentally reconstruct
      the 3-dimensional anatomy using 2D views. Over the past 20 years, a number of 3
      dimensional ultrasound imaging approaches have been developed. We have developed
      an approach that is based on a mechanical mechanism to move any conventional
      ultrasound transducer while 2D images are collected rapidly and reconstructed
      into a 3D image. In this presentation, 3D ultrasound imaging approaches will be
      described for use in image-guided interventions. 

PMID- 25571402
TI  - A parallel wire robot for epicardial interventions.
AB  - This paper describes the design and preliminary testing of a planar parallel wire
      robot that adheres to the surface of the beating heart and provides a stable
      platform for minimally invasive epicardial therapies. The device is deployed
      through a small subxiphoid skin incision and attaches to the heart using suction.
      This methodology obviates mechanical stabilization and lung deflation, which are
      typically required during minimally invasive beating-heart surgery. The prototype
      design involves three vacuum chambers connected by two flexible arms. The
      chambers adhere to the epicardium, forming the vertices of a triangular base
      structure. Three cables connect a movable end-effector head to the three bases;
      the cables then pass out of the body to external actuators. The surgical tool
      moves within the triangular workspace to perform injections, ablation, or other
      tasks on the beating heart. Tests in vitro and in vivo were conducted to
      demonstrate the capabilities of the system. Tests in vivo successfully
      demonstrated the ability to deploy through a subxiphoid incision, adhere to the
      surface of the beating heart, move the surgical tool head within the robot's
      workspace, and perform injections into the myocardium. 

PMID- 25571403
TI  - Design and development of a mobile image overlay system for needle interventions.
AB  - Previously, a static and adjustable image overlay systems were proposed for
      aiding needle interventions. The system was either fixed to a scanner or mounted
      over a large articulated counterbalanced arm. Certain drawbacks associated with
      these systems limited the clinical translation. In order to minimize these
      limitations, we present the mobile image overlay system with the objective of
      reduced system weight, smaller dimension, and increased tracking accuracy. The
      design study includes optimal workspace definition, selection of display device,
      mirror, and laser source. The laser plane alignment, phantom design, image
      overlay plane calibration, and system accuracy validation methods are discussed.
      The virtual image is generated by a tablet device and projected into the patient
      by using a beamsplitter mirror. The viewbox weight (1.0 kg) was reduced by 8.2
      times and image overlay plane tracking precision (0.21 mm, STD = 0.05) was
      improved by 5 times compared to previous system. The automatic self-calibration
      of the image overlay plane was achieved in two simple steps and can be done away
      from patient table. The fiducial registration error of the physical phantom to
      scanned image volume registration was 1.35 mm (STD = 0.11). The reduced system
      weight and increased accuracy of optical tracking should enable the system to be
      hand held by the physician and explore the image volume over the patient for
      needle interventions.

PMID- 25571404
TI  - Injection-depth-locking axial motion guided handheld micro-injector using CP
      SSOCT.
AB  - This paper presents a handheld micro-injector system using common-path swept
      source optical coherence tomography (CP-SSOCT) as a distal sensor with highly
      accurate injection-depth-locking. To achieve real-time, highly precise, and
      intuitive freehand control, the system used graphics processing unit (GPU) to
      process the oversampled OCT signal with high throughput and a smart customized
      motion monitoring control algorithm. A performance evaluation was conducted with
      60-insertions and fluorescein dye injection tests to show how accurately the
      system can guide the needle and lock to the target depth. The evaluation tests
      show our system can guide the injection needle into the desired depth with 4.12
      um average deviation error while injecting 50 nl of fluorescein dye.

PMID- 25571405
TI  - A stereotaxic image-guided surgical robotic system for depth electrode insertion.
AB  - This article constructs a surgical robotic system for the stereotactic insertion
      of the depth electrodes for stereoelectroencephalogram (SEEG). The purpose is to
      increase the efficiency of the stereotactic insertion of the electrodes. The
      registration method of this system is based on the noninvasive fiducial markers.
      After registration, the robotic system can locate all the preplanned electrode
      trajectories automatically. The validation of this proposed system has been
      performed by testing the time consumption of the system workflow and measuring
      the positioning accuracy on phantoms. From the result, we conclude that this
      surgical robotic system can assist surgeons in performing the stereotactic
      insertion of the depth electrodes accurately and efficiently. 

PMID- 25571406
TI  - Human pluripotent stem cell tools for cardiac optogenetics.
AB  - It is likely that arrhythmias should be avoided for therapies based on human
      pluripotent stem cell (hPSC)-derived cardiomyocytes (CM) to be effective. Towards
      achieving this goal, we introduced light-activated channelrhodopsin-2 (ChR2), a
      cation channel activated with 480 nm light, into human embryonic stem cells
      (hESC). By using in vitro approaches, hESC-CM are able to be activated with
      light. ChR2 is stably transduced into undifferentiated hESC via a lentiviral
      vector. Via directed differentiation, hESC(ChR2)-CM are produced and subjected to
      optical stimulation. hESC(ChR2)-CM respond to traditional electrical stimulation
      and produce similar contractility features as their wild-type counterparts but
      only hESC(ChR2)-CM can be activated by optical stimulation. Here it is shown that
      a light sensitive protein can enable in vitro optical control of hESC-CM and that
      this activation occurs optimally above specific light stimulation intensity and
      pulse width thresholds. For future therapy, in vivo optical stimulation along
      with optical inhibition could allow for acute synchronization of implanted hPSC
      CM with patient cardiac rhythms. 

PMID- 25571407
TI  - Applications of microfluidics for studying growth mechanisms of tip growing
      pollen tubes.
AB  - Pollen tube, the fastest tip growing plant cell, plays essential role in life
      cycle of flowering plants. It is extremely sensitive to external cues and this
      makes it as a suitable cellular model for characterizing the cell response to the
      influence of various signals involved in cellular growth metabolism. For in-vitro
      study of pollen tube growth, it is essential to provide an environment the mimics
      the internal microenvironment of pollen tube in flower. In this context,
      microfluidic platforms take advantage of miniaturization for handling small
      volume of liquids, providing a closed environment for in-vitro single cell
      analysis, and characterization of cell response to external cues. These platforms
      have shown their ability for high-throughput cellular analysis with increased
      accuracy of experiments, and reduced cost and experimental times. Here, we review
      the recent applications of microfluidic devices for investigating several aspects
      of biology of pollen tube elongation. 

PMID- 25571408
TI  - Cytotoxicity of synthesized Iron Oxide nanoparticles: toward novel biomarkers of
      colon cancer.
AB  - In this paper we present the preliminary results of a novel biological analysis
      platform for early colon cancer detection using magnetic separation of magnetized
      markers. The platform consists of a microfluidic structure integrated with
      biosensors. Super-Paramagnetic Iron Oxide nanoparticles (SPIO-NPs) were
      functionalized with purified DNA Aptamer and their synthesis is described. In
      this paper, we also present the physicochemical results of the synthesized
      SPIO/Au-NPs characterized by TEM and XRD. Toxicity of our synthesized biomarkers
      on HCT116 cell line is discussed. Based on our findings, a concentration of
      1mg/ml of our biomarkers added to 5 * 105 cells per well has no effect the
      viability of the human cells even after 24 hours. 

PMID- 25571409
TI  - Dynamic response of axonal microtubules under suddenly applied end forces.
AB  - Axon is a filament in neuronal system and axonal microtubules are bundles in
      axons. In axons, microtubules are coated with microtubule-associated protein tau,
      a natively unfolded profuse filamentous protein in the central nervous system.
      These proteins are responsible for the cross-linked structure of the axonal
      microtubule bundles. Through complimentary dimerization with other tau proteins,
      bridges are formed to nearby microtubules to create bundles. The transverse
      reinforcement of microtubules by cross-linking to the cytoskeleton has been shown
      to enhance their ability to bear compressive loads. Though microtubules are
      conventionally regarded as bearing compressive loads, in certain circumstances
      such as in traumatic stretch injury, they are placed in tension. We employ
      Standard Linear Solid, a viscoelastic model, to computationally simulate
      microtubules. This study investigates the dynamic response of two dimensional
      axonal microtubules under suddenly applied end forces. We obtain the results for
      steady state behavior of axonal microtubule for different forces. 

PMID- 25571410
TI  - Thermal effect of dielectrophoresis manipulation on cerebrospinal fluid.
AB  - This paper introduces an investigation on the thermal effects of
      dielectrophoresis on cerebrospinal fluid (CSF). It highlights the temperature
      propagation in CSF according to applied voltage and generated electrical field in
      a limited area of the brain. Through the described study, the temperature
      increase is considerable in the close surrounding area of electrodes where
      applied voltage goes up to 20 V(rms) in order to generate dielectrophoretic
      forces for CSF sampling. Matlab simulations detailed in this work are based on
      the assumption that the propagation of temperature in CSF is linear. The
      objective of this research is to study the thermal side effects of direct
      measurements and manipulations of neurotransmitters in the brain versus in
      channel measurement of neurotransmitter concentration. Indeed, according to
      simulation results, if the temperature in the top of electrodes is 46.85  degrees
      C then it will decrease only to 45.35  degrees C at 1 mm away from electrode
      surface.

PMID- 25571411
TI  - A real-time adaptive oxygen transfer rate estimator for metabolism tracking in
      Escherichia coli cultures.
AB  - Oxygen transfer rate (OTR) is the most significant signal for aerobic bioprocess
      control, since most microbic metabolic activity relies on oxygen consumption.
      However, accurate estimation of OTR is challenging due to the difficulty of
      determining uncertain oxygen transfer parameters and system dynamics. This paper
      presents an adaptive estimator, which incorporates exhaust gas, stir speed and
      dissolved oxygen measurements, to predict the real-time OTR. The design of this
      estimator takes into account the headspace dilution effect, off-gas sensor
      dynamics and uncertain oxygen transfer parameters. Through simulation the
      estimated real-time OTR is shown to accurately track quick changes of oxygen
      demand in the culture. Thus, it can be applied to a variety of controls and
      estimation purposes, such as determining when the culture is in oxidative or
      overflow metabolism. 

PMID- 25571412
TI  - Functional assessment of the Vanderbilt Multigrasp myoelectric hand: a continuing
      case study.
AB  - This paper presents a case study involving the functional assessment of the
      Vanderbilt Multigrasp (VMG) hand prosthesis on a single transradial amputee
      subject. In particular, a transradial amputee subject performed the Southampton
      Hand Assessment Procedure (SHAP) using the hand prosthesis and multigrasp
      myoelectric controller in a series of experimental sessions occurring over a
      multi-week time span. The subject's index of function (IoF) improved with each
      session, although essentially plateaued after the fourth session, resulting in a
      IoF score of 87, which compares favorably to SHAP scores published in previous
      studies. 

PMID- 25571413
TI  - Recovery strategy identification throughout swing phase using kinematic data from
      the tripped leg.
AB  - Falls are a large concern for individuals with lower limb amputations. Advanced
      powered prosthetic devices have the potential to quickly intervene after
      perturbations and help avoid a fall, but active balance recovery mechanisms have
      yet to be implemented. We investigated the feasibility of a realtime pattern
      recognition system for identification of trip recovery strategies. We tripped
      able-bodied subjects multiple times throughout swing phase and investigated the
      classification of walking, elevating and lowering strategies. Linear discriminant
      analysis was used throughout swing phase to classify kinematic data from the
      tripped leg. Window parameters that maximized classification accuracy were chosen
      from lengths of 50 to 200 ms and increments of 10 to 50 ms. We compared the
      performance of a single- and a two-stage (trip detection followed by strategy
      identification) classifier architecture. Optimal window length varied by
      classification stage, and window increment did not affect accuracy. The two-stage
      architecture performed significantly better overall, achieving a 92% median
      (range 88%-96%) accuracy across subjects compared to 88% (84%-96%) with the
      single-stage architecture. Most of the errors occurred immediately after the
      trip, with accuracies plateauing within 100 ms. Our results suggest that
      algorithms using data that can be measured from sensors embedded in robotic
      assistive devices could be used to trigger active balance restoring strategies
      following trips throughout swing phase. 

PMID- 25571414
TI  - A walking controller for a powered ankle prosthesis.
AB  - This paper describes a walking controller implemented on a powered ankle
      prosthesis prototype and assessed by a below-knee amputee subject on a treadmill
      at three speeds. The walking controller is a finite state machine which emulates
      a series of passive impedance functions at the joint in order to reproduce the
      behavior of a healthy joint. The assessments performed demonstrate the ability of
      the powered prosthesis prototype and walking controller to reproduce essential
      biomechanical aspects (i.e. joint angle, torque, and power profiles) of the
      healthy joint, especially relative to a passive prosthesis. 

PMID- 25571415
TI  - Estimation of crank angle for cycling with a powered prosthesis.
AB  - In order for a prosthesis to restore power generation during cycling, it must
      supply torque in a manner that is coordinated with the motion of the bicycle
      crank. This paper outlines an algorithm for the real time estimation of the
      angular position of a bicycle crankshaft using only measurements internal to an
      intelligent knee and ankle prosthesis. The algorithm assumes that the
      rider/prosthesis/bicycle system can be modeled as a four-bar mechanism. Assuming
      that a prosthesis can generate two independent angular measurements of the
      mechanism (in this case the knee angle and the absolute orientation of the
      shank), Freudenstein's equation can be used to synthesize the mechanism
      continuously. A recursive least-squares algorithm is implemented to estimate the
      Freudenstein coefficients, and the resulting link lengths are used to reformulate
      the equation in terms of input-output relationships mapping both measured angles
      to the crank angle. Using two independent measurements allows the algorithm to
      uniquely determine the crank angle from multi-valued functions. In order to
      validate the algorithm, a bicycle was mounted on a trainer and configured with
      the prosthesis using an artificial hip joint attached to the seat post. Motion
      capture was used to monitor the mechanism for forward and backward pedaling and
      the results are compared to the output of the presented algorithm. Once the
      parameters have converged, the algorithm is shown to predict the crank angle
      within 15 degrees  of the externally measured value throughout the entire crank
      cycle during forward rotation. 

PMID- 25571416
TI  - A miniaturised actuation system embedded in an instrumented knee implant for
      postoperative ligament imbalance correction.
AB  - During Total Knee Arthroplasty surgery, the orthopaedic surgeon has to set up
      proper balance conditions for the two lateral ligaments of the knee. Such
      ligament tensioning procedure is performed manually and mainly depends on the
      surgeon's experience. Unfortunately, inaccuracies are unavoidable and may give
      rise to serious postoperative complications. In the worst-case scenario, the only
      solution to this problem is represented by revision surgery. In order to cope
      with this problem, this work proposes a novel instrumented tibial component able
      to detect knee imbalance conditions in the postoperative period. A miniaturised
      actuation system embedded in the tibial baseplate allows to restore optimal
      balance conditions without resorting to revision surgery. 

PMID- 25571417
TI  - A novel design method of anthropomorphic prosthetic hands for reproducing human
      hand grasping.
AB  - Because hand is often used for grasping, developing a design of prosthetic hands,
      particularly light and compact underactuated anthropomorphic transradial
      prostheses for reproducing human hand complex grasping is crucial for upper-limb
      amputees. Obviously, the less the number of actuators is, the worse the
      anthropomorphic motion capability of the prosthetic hands will be. This paper
      aims to design a transmission mechanism with few motors actuating fingers which
      could serve the relatively accurate grasp movement of a human hand and has the
      potential to be embedded in a palm including the motors. We start with
      establishing an index for evaluating the anthropomorphic motion capability of a
      prosthetic hand. Based on the optimization of this index, we determine the number
      of actuators in fingers and the transmission relationship between the actuators
      and the metacarpophalangeal(MCP) joints. Then, a new design method to
      mechanically implement the transmission relationship based on a novel
      decomposition of transmission matrix is proposed in this paper. Utilizing this
      method, we obtained the final mechanical structure of a new prosthetic hand. 

PMID- 25571418
TI  - Neural markers for immediate performance accuracy in a Stroop color-word matching
      task: an event-related potentials analysis.
AB  - The present study examined the neural markers measured in event-related
      potentials (ERPs) for immediate performance accuracy during a cognitive task with
      less conflict, i.e., a Stroop color-word matching task, in which participants
      were required to judge the congruency of two feature dimensions of a stimulus. In
      an effort to make ERP components more specific to distinct underlying neural
      substrates, recorded EEG signals were firstly dissolved into multiple independent
      components (ICs) using independent component analysis (ICA). Thereafter,
      individual ICs with prominent sensory- or cognitive-related ERP components were
      selected to separately reconstruct scalp EEG signals at representative channels,
      from which ERP waveforms were built, respectively. Statistical comparisons on
      amplitudes of stimulus-locked ERP components, i.e., prefrontal P2 and N2,
      parietal P3, bilateral occipital P1 and N1, revealed significant reduced P3
      amplitude in error trials than in correct trials. In addition, significant
      evident ERN was also observed in error trials but not in correct trials.
      Considering the temporal locus of semantic conflict in the present task, we
      concluded that reduced P3 amplitude in error trials reflect impaired resolving
      process of semantic conflict, which further lead to a performance error in the
      Stroop color-word matching task. 

PMID- 25571419
TI  - The effects of perceiving color in living environment on QEEG, oxygen saturation,
      pulse rate, and emotion regulation in humans.
AB  - Light and color have been shown to have substantial physical, psychological and
      sociological effects on humans. Hence, an investigation on the effect of changes
      in light and color to the biological signals is a challenging problem. Five
      participants were measured the oxygen saturation (SpO2), pulse rate, and
      quantitative electroencephalogram (QEEG) in six colors (white, blue, green,
      yellow, red and black) of living environment for 5 minutes per color. Then all
      participants were asked to answer the emotional questionnaire of BRUMS and color
      performance for each color environment. The results showed brain activity of high
      beta wave (25-30 Hz) that associated with alertness, agitation, mental activity,
      and general activation of mind and body functions (at frontal lobes and temporal
      lobes) in red and yellow colored rooms were higher than blue, green, white and
      black colored rooms, respectively. It also had the relationship with the
      psychological effect (BRUMS). The amplitude asymmetry of beta wave (12-25 Hz) was
      highly attenuated in warm color (red and yellow colored rooms), moderately
      attenuated in cool color (green and blue colored room) and little attenuated in
      white and black colored rooms. The BRUMS showed that red and yellow yielded
      significant effect on anger (F = 4.966, p = 0.002) and confusion (F=3.853,
      p=0.008). Red and green color yielded high effect on vigor. Green color did not
      affect the depression. Blue color yielded moderate effect on confusion, tension
      and fatigue. White and black colors yielded low effect on any mood, but black
      color had no effect on vigor. In addition, we cannot observe any significant
      changes of pulse rate and blood oxygen saturation in each color. The results can
      possibly be used as the recommendation to design the room for either normal
      people or patients.

PMID- 25571420
TI  - Functional range of movement of the hand: declination angles to reachable space.
AB  - The measurement of the range of hand joint movement is an essential part of
      clinical practice and rehabilitation. Current methods use three finger joint
      declination angles of the metacarpophalangeal, proximal interphalangeal and
      distal interphalangeal joints. In this paper we propose an alternate form of
      measurement for the finger movement. Using the notion of reachable space instead
      of declination angles has significant advantages. Firstly, it provides a visual
      and quantifiable method that therapists, insurance companies and patients can
      easily use to understand the functional capabilities of the hand. Secondly, it
      eliminates the redundant declination angle constraints. Finally, reachable space,
      defined by a set of reachable fingertip positions, can be measured and
      constructed by using a modern camera such as Creative Senz3D or built-in hand
      gesture sensors such as the Leap Motion Controller. Use of cameras or optical
      type sensors for this purpose have considerable benefits such as eliminating and
      minimal involvement of therapist errors, non-contact measurement in addition to
      valuable time saving for the clinician. A comparison between using declination
      angles and reachable space were made based on Hume's experiment on functional
      range of movement to prove the efficiency of this new approach. 

PMID- 25571421
TI  - A comparison of methods to detect postural transitions using a single tri-axial
      accelerometer.
AB  - Two algorithms for evaluating postural transitions (PTs) in cohorts of 40 healthy
      younger and 40 older adults are described and evaluated. The time of sit-to-stand
      (SiSt) and stand-to-sit (StSi) transitions and their duration were measured with
      two tri-axial accelerometers, one on the chest and one on the lower back. Each
      algorithm was optimized for these sensor placements. The first algorithm for
      sensor placement on the chest used a scalar product and vertical velocity
      estimates. The second algorithm for sensor placement on the lower back used a
      vector magnitude and a discrete wavelet transform. Both algorithms performed
      excellently in PT classification for younger and older adults (>86%). However,
      the chest based sensor and algorithm were better for estimating transition
      duration (TD) with ICCs to video analysis ranging from 0.678 to 0.969. 

PMID- 25571422
TI  - Evaluation of the workload and drowsiness during car driving by using high
      resolution EEG activity and neurophysiologic indices.
AB  - Sleep deprivation and/or a high workload situation can adversely affect driving
      performance, decreasing a driver's capacity to respond effectively in dangerous
      situations. In this context, to provide useful feedback and alert signals in real
      time to the drivers physiological and brain activities have been increasingly
      investigated in literature. In this study, we analyze the increase of cerebral
      workload and the insurgence of drowsiness during car driving in a simulated
      environment by using high resolution electroencephalographic techniques (EEG) as
      well as neurophysiologic variables such as heart rate (HR) and eye blinks rate
      (EBR). The simulated drive tasks were modulated with five levels of increasing
      difficulty. A workload index was then generated by using the EEG signals and the
      related HR and EBR signals. Results suggest that the derived workload index is
      sensitive to the mental efforts of the driver during the different drive tasks
      performed. Such workload index was based on the estimation the variation of EEG
      power spectra in the theta band over prefrontal cortical areas and the variation
      of the EEG power spectra over the parietal cortical areas in alpha band. In
      addition, results suggested as HR increases during the execution of the difficult
      driving tasks while instead it decreases at the insurgence of the drowsiness.
      Finally, the results obtained showed as the EBR variable increases of its values
      when the insurgence of drowsiness in the driver occurs. The proposed workload
      index could be then used in a near future to assess on-line the mental state of
      the driver during a drive task. 

PMID- 25571423
TI  - Topological changes of the effective connectivity during the working memory
      training.
AB  - Working memory (WM) refers to the retention of information over a short period of
      time. Accumulated evidence showed that training WM would lead to beneficial
      effects in untrained tasks, which could be attributed to the strengthening of the
      functional connections between brain regions through repeated training task. In
      this proof of concept investigation, we applied a graph theoretical approach to
      analyze the early changes of functional connectivity from two subjects undergoing
      a spatial n-back WM training task for three continuous days. A significant
      decreased clustering coefficient and normalized shortest path length was
      revealed, suggesting a reduced local efficiency with an increased global
      efficiency after WM training. Our findings thereby provide insightful
      implications for understanding the mechanisms of brain dynamics in cognitive
      training. 

PMID- 25571424
TI  - Modeling dermatome selectivity of single-and multiple-current source spinal cord
      stimulation systems.
AB  - A recently published computational modeling study of spinal cord stimulation
      (SCS) predicted that a multiple current source (MCS) system could generate a
      greater number of central points of stimulation in the dorsal column (DC) than a
      single current source (1 CS) system. However, the clinical relevance of this
      finding has not been established. The objective of this work was to compare the
      dermatomal zone selectivity of MCS and 1 CS systems. A finite element method
      (FEM) model was built with a representation of the spinal cord anatomy and a 2 *
      8 paddle electrode array. Using a contact configuration with two aligned
      tripoles, the FEM model was used to solve for DC field potentials across
      incremental changes in current between the two cathodes, modeling the MCS and 1
      CS systems. The activation regions within the DC were determined by coupling the
      FEM output to a biophysical nerve fiber model, and coverage was mapped to
      dermatomal zones. Results showed marginal differences in activated dermatomal
      zones between 1 CS and MCS systems. This indicates that a MCS system may not
      provide incremental therapeutic benefit as suggested in prior analysis.

PMID- 25571425
TI  - BRAIN initiative: fast and parallel solver for real-time monitoring of the eddy
      current in the brain for TMS applications.
AB  - This paper introduce a fast and efficient solver for simulating the induced
      (eddy) current distribution in the brain during transcranial magnetic stimulation
      procedure. This solver has been integrated with MRI and neuronavigation software
      to accurately model the electromagnetic field and show eddy current in the head
      almost in real-time. To examine the performance of the proposed technique, we
      used a 3D anatomically accurate MRI model of the 25 year old female subject. 

PMID- 25571426
TI  - Computational modeling analysis of a spinal cord stimulation paddle lead reveals
      broad, gapless dermatomal coverage.
AB  - Spinal cord stimulation (SCS) is an effective therapy for treating chronic pain.
      The St. Jude Medical PENTA(TM) paddle lead features a 4 * 5 contact array for
      achieving broad, selective coverage of dorsal column (DC) fibers. The objective
      of this work was to evaluate DC activation regions that correspond to dermatomal
      coverage with use of the PENTA lead in conjunction with a lateral sweep
      programming algorithm. We used a two-stage computational model, including a
      finite element method model of field potentials in the spinal cord during
      stimulation, coupled to a biophysical cable model of mammalian, myelinated nerve
      fibers to determine fiber activation within the DC. We found that across contact
      configurations used clinically in the sweep algorithm, the activation region
      shifted smoothly between left and right DC, and could achieve gapless medio
      lateral coverage in dermatomal fiber tract zones. Increasing stimulation
      amplitude between the DC threshold and discomfort threshold led to a greater area
      of activation and number of dermatomal zones covered on the left and/or right DC,
      including L1-2 zones corresponding to dermatomes of the lower back. This work
      demonstrates that the flexibility in contact selection offered by the PENTA lead
      may enable patient-specific tailoring of SCS.

PMID- 25571427
TI  - A computational model for bipolar deep brain stimulation of the subthalamic
      nucleus.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to
      reduce some of the symptoms of advanced, levodopa-responsive Parkinson's disease
      that are not adequately controlled with medication. However, the precise
      mechanism of the therapeutic action of DBS is still unclear. Stimulation-induced
      side effects are not uncommon and require electrical "dose" adjustments.
      Quantitative methods are needed to fully characterize the electric field in the
      deep brain region that surrounds the electrodes in order to help with adjustments
      and maximize the efficacy of the device. Herein we report a magnetic resonance
      imaging (MRI)-based head model proposed for analysis of fields generated by deep
      brain stimulation (DBS). The model was derived from multimodal image data at
      0.5mm isotropic spatial resolution and distinguishes 142 anatomical structures,
      including the basal ganglia and 38 nuclei of the thalamus. Six bipolar electrode
      configurations (1-2, 1-3, 1-4, 2-3, 2-4, 3-4) were modeled in order to assess the
      effects of the inter-electrode distance of the electric field. Increasing the
      distance between the electrodes results in an attenuated stimulation, with up to
      25% reduction in electric field amplitude delivered (2-3 vs. 1-4). The map of the
      deep brain structures provided a highly precise anatomical detail which is useful
      for the quantitative assessment of current spread around the electrode and a
      better evaluation of the stimulation setting for the treatment optimization. 

PMID- 25571428
TI  - On-off closed-loop control of vagus nerve stimulation for the adaptation of heart
      rate.
AB  - Vagus nerve stimulation (VNS) is a potential therapeutic approach in a number of
      clinical applications. Although VNS is commonly delivered in an open-loop
      approach, it is now recognized that closed-loop approaches may be necessary to
      optimize the therapy and minimize side effects of neuro-stimulation devices. In
      this paper, we describe a prototype system for real-time control of the
      instantaneous heart rate, working synchronously with the heart period. As a first
      step, an on-off control method has been integrated. The system is evaluated on
      one sheep with induced heart failure, showing the interest of the proposed
      approach. 

PMID- 25571429
TI  - Health care sensor--based systems for point of care monitoring and diagnostic
      applications: a brief survey.
AB  - Continuous, real-time remote monitoring through medical point--of--care (POC)
      systems appears to draw the interest of the scientific community for healthcare
      monitoring and diagnostic applications the last decades. Towards this direction a
      significant merit has been due to the advancements in several scientific fields.
      Portable, wearable and implantable apparatus may contribute to the betterment of
      today's healthcare system which suffers from fundamental hindrances. The number
      and heterogeneity of such devices and systems regarding both software and
      hardware components, i.e sensors, antennas, acquisition circuits, as well as the
      medical applications that are designed for, is impressive. Objective of the
      current study is to present the major technological advancements that are
      considered to be the driving forces in the design of such systems, to briefly
      state the new aspects they can deliver in healthcare and finally, the
      identification, categorization and a first level evaluation of them.

PMID- 25571430
TI  - A cascaded two-step Kalman filter for estimation of human body segment
      orientation using MEMS-IMU.
AB  - Orientation of human body segments is an important quantity in many biomechanical
      analyses. To get robust and drift-free 3-D orientation, raw data from miniature
      body worn MEMS-based inertial measurement units (IMU) should be blended in a
      Kalman filter. Aiming at less computational cost, this work presents a novel
      cascaded two-step Kalman filter orientation estimation algorithm. Tilt angles are
      estimated in the first step of the proposed cascaded Kalman filter. The estimated
      tilt angles are passed to the second step of the filter for yaw angle
      calculation. The orientation results are benchmarked against the ones from a
      highly accurate tactical grade IMU. Experimental results reveal that the proposed
      algorithm provides robust orientation estimation in both kinematically and
      magnetically disturbed conditions. 

PMID- 25571431
TI  - Wearable blood flowmeter appcessory with low-power laser Doppler signal
      processing for daily-life healthcare monitoring.
AB  - A new appcessory for monitoring peripheral blood flow in daily life consists of a
      wearable laser Doppler sensor device and a cooperating smart phone application.
      Bluetooth Low Energy connects them wirelessly. The sensor device features
      ultralight weight of 15 g and an intermittent signal processing technique that
      reduces power consumption to only 7 mW at measurement intervals of 0.1 s. These
      features enable more than 24-h continuous monitoring of peripheral blood flow in
      daily life, which can provide valuable vital-sign information for healthcare
      services. 

PMID- 25571432
TI  - Novel wireless-communicating textiles made from multi-material and minimally
      invasive fibers.
AB  - The ability to integrate multiple materials into miniaturized fiber structures
      enables the realization of novel biomedical textile devices with higher-level
      functionalities and minimally-invasive attributes. In this work, we present novel
      textile fabrics integrating unobtrusive multi-material fibers that communicate
      through 2.4 GHz wireless networks with excellent signal quality. The conductor
      elements of the textiles are embedded within the fibers themselves, providing
      electrical and chemical shielding against the environment, while preserving the
      mechanical and cosmetic properties of the garments. These multi-material fibers
      combine insulating and conducting materials into a well-defined geometry, and
      represent a cost-effective and minimally-invasive approach to sensor fabrics and
      bio-sensing textiles connected in real time to mobile communications
      infrastructures, suitable for a variety of health and life science applications. 

PMID- 25571433
TI  - Ambulatory measurement of foot kinematics using wearable ultrasonic sensors.
AB  - In this paper, an ultrasonic-based system for foot parameters measurement has
      been proposed and investigated. An extended Kalman filtering-based methodology
      has been developed to extract foot parameters including step length, stride
      length and cycle time from horizontal displacement during walking. The system
      comprises of one ultrasonic transmitter (mobile) and four ultrasonic receivers
      (anchors) with fixed known positions. A Radio Frequency (RF) module is used in
      our system not only to provide synchronization clock between the mobile and
      anchors, but also to transmit collected data wirelessly to reduce the wires used.
      To evaluate the performance of the proposed system, the 2-dimensional foot
      displacement and the foot parameters were measured and validated against the
      reference camera motion capture system. These experiment results demonstrate the
      capability of the proposed system being used as a gait analysis tool for
      rehabilitation and other medical applications. 

PMID- 25571434
TI  - Measurement of high-resolution mechanical contraction of cardiac muscle by
      induced eddy current.
AB  - There are many types of devices which help to manage a personal health conditions
      such as heartbeat chest belt, pedometer and smart watch. And the most common
      device has the relationship with heart rate or ECG data. However, users have to
      attach some electrode or fasten the belt on the bare skin to measure bio-signal
      information. Therefore, most of people want more convenient and short-ready-time
      and no-need to attach electrode. In this paper, we proposed the high-resolution
      measuring system of mechanical activity of cardiac muscle and thereby measure
      heartbeat. The principle of the proposed measuring method is that the alternating
      current generate alternating magnetic field around coil. This primary magnetic
      field induces eddy current which makes magnetic field against primary coil in the
      nearby objects. To measure high-resolution changes of the induced secondary
      magnetic fields, we used digital Phase-locked loop(PLL) circuit which provides
      more high-resolution traces of frequency changes than the previous studies based
      on digital frequency counter method. As a result of our preliminary experiment,
      peak-peak intervals of the proposed method showed high correlation with R-R
      intervals of clinical ECG signals(r=0.9249). Also, from signal traces of the
      proposed method, we might make a conjecture that the contraction of atrium or
      ventricle is reflected by changing conductivity of cardiac muscle which is
      beating ceaselessly. 

PMID- 25571435
TI  - DocBot: a novel clinical decision support algorithm.
AB  - DocBot is a web-based clinical decision support system (CDSS) that uses patient
      interaction and electronic health record analytics to assist medical
      practitioners with decision making. It consists of two distinct HTML interfaces:
      a preclinical form wherein a patient inputs symptomatic and demographic
      information, and an interface wherein a medical practitioner views patient
      information and analysis. DocBot comprises an improved software architecture that
      uses patient information, electronic health records, and etiologically relevant
      binary decision questions (stored in a knowledgebase) to provide medical
      practitioners with information including, but not limited to medical assessments,
      treatment plans, and specialist referrals. 

PMID- 25571436
TI  - Foot-mounted inertial measurement unit for activity classification.
AB  - This paper proposes a classification technique for daily base activity
      recognition for human monitoring during physical therapy in home. The proposed
      method estimates the foot motion using single inertial measurement unit, then
      segments the motion into steps classify them by template-matching as walking,
      stairs up or stairs down steps. The results show a high accuracy of activity
      recognition. Unlike previous works which are limited to activity recognition, the
      proposed approach is more qualitative by providing similarity index of any
      activity to its desired template which can be used to assess subjects
      improvement. 

PMID- 25571437
TI  - Characterization of the respiratory and heart beat signal from an air pressure
      based ballistocardiographic setup.
AB  - Off-body detection of respiratory and cardiac activity presents an enormous
      opportunity for general health, stress and sleep quality monitoring. The
      presented setup detects the mechanical activity of both heart and lungs by
      measuring pressure difference fluctuations between two air volumes underneath the
      chest area of the subject. The registered signals were characterized over four
      different sleep postures, three different base air pressures within the air
      volumes and three different mattress top layer materials. Highest signal strength
      was detected in prone posture for both the respiratory and heart beat signal.
      Respiratory signal strength was the lowest in supine posture, while heart beat
      signal strength was lowest for right lateral. Heart beat cycle variability was
      highest in prone and lowest in supine posture. Increasing the base air pressure
      caused a reduction in signal amplitude for both the respiratory and the heart
      beat signal. A visco-elastic poly-urethane foam top layer had significantly
      higher respiration amplitude compared to high resilient poly-urethane foam and
      latex foam. For the heart beat signal, differences between the top layers were
      small. The authors conclude that, while the influence of the mattress top layer
      material is small, the base air pressure can be tuned for optimal mechanical
      transmission from heart and lungs towards the registration setup. 

PMID- 25571438
TI  - Portable tongue-supported human computer interaction system design and
      implementation.
AB  - Tongue supported human-computer interaction (TSHCI) systems can help critically
      ill patients interact with both computers and people. These systems can be
      particularly useful for patients suffering injuries above C7 on their spinal
      vertebrae. Despite recent successes in their application, several limitations
      restrict performance of existing TSHCI systems and discourage their use in real
      life situations. This paper proposes a low-cost, less-intrusive, portable and
      easy to use design for implementing a TSHCI system. Two applications of the
      proposed system are reported. Design considerations and performance of the
      proposed system are also presented. 

PMID- 25571439
TI  - Empowering patients to perform physical therapy at home.
AB  - In this paper we address the problem of patient adherence to physical therapy
      using a sensor-enabled virtual reality gaming interface that motivates users to
      complete their exercises while collecting quantitative data. The system also
      allows the therapist to monitor and interact with patients remotely providing
      reinforcing feedback and support with the CollaboRhythm care delivery platform.
      The data collected with this system enables the therapist and the patient to make
      informed decisions about patient treatment and exercise regimens based on the
      patient progress. The system is capable of supporting a wide array of
      rehabilitation scenarios with remote collaboration. A knee replacement scenario
      was tested with an experimental protocol involving 16 healthy participants. The
      results show both quantitatively and qualitatively that patients can learn
      intuitively to perform their physical therapy exercises on a remote environment
      without further human intervention. 

PMID- 25571440
TI  - Proposal of a novel remote command and control configuration extension for
      interoperable Personal Health Devices (PHD) based on ISO/IEEE11073 standard.
AB  - New use cases to extend the interoperability standard ISO/IEEE11073 (X73) were
      found during the development of recent specializations. These use cases expose
      the need of remote command and control extensions to allow managers to configure
      agents through the standard. This paper presents a proposal for an extension of
      remote control and configuration service able to standardize a general procedure
      within the newest branch of this standard called X73 for Personal Health Devices
      (X73PHD). In order to develop a service for remote control, several approaches
      have been studied and discussed in the Personal Health Device Working Group (PHD
      WG). The final solution is defined following the PHD-WG guidelines and integrated
      with the Optimized Exchange Protocol (X73-20601) and device specializations (X73
      104xx). Previous works such as the classic command and control and the extended
      services packages from X73-10201 and X73-20301, respectively, have also been
      taken into account. 

PMID- 25571441
TI  - Statistical pattern analysis of blood vessel features on retina images and its
      application to blood vessel mapping algorithms.
AB  - Computer based modeling and analysis of blood vessel (BV) networks is essential
      for automated detection and tracking of anomalies and structural changes in
      retina images. Among many published techniques for automated BV mapping, optimal
      selection of thresholds to delineate BV pixels from their background pixels
      remains an open problem. In this paper we propose a novel representation of a BV
      pixel feature, daisy graph, using rotational contrast transform (RCT), and two
      feature descriptors energy E(p) and symmetry difference S(p) of the daisy graph.
      Non-BV pixels are separated from BV and boundary pixels based on E(p). Fitness of
      the lognormal distribution to S(p) of BV pixels with negative E(p) has been
      tested extensively for images in the STARE and DRIVE databases. Based on
      statistical pattern analysis in the feature space, we propose a fast self
      calibrated BV mapping algorithm which achieve comparable and statistically sound
      performance as contemporary solutions.

PMID- 25571442
TI  - Comprehensive automatic assessment of retinal vascular abnormalities for computer
      assisted retinopathy grading.
AB  - One of the most important signs of systemic disease that presents on the retina
      is vascular abnormalities such as in hypertensive retinopathy. Manual analysis of
      fundus images by human readers is qualitative and lacks in accuracy, consistency
      and repeatability. Present semi-automatic methods for vascular evaluation are
      reported to increase accuracy and reduce reader variability, but require
      extensive reader interaction; thus limiting the software-aided efficiency.
      Automation thus holds a twofold promise. First, decrease variability while
      increasing accuracy, and second, increasing the efficiency. In this paper we
      propose fully automated software as a second reader system for comprehensive
      assessment of retinal vasculature; which aids the readers in the quantitative
      characterization of vessel abnormalities in fundus images. This system provides
      the reader with objective measures of vascular morphology such as tortuosity,
      branching angles, as well as highlights of areas with abnormalities such as
      artery-venous nicking, copper and silver wiring, and retinal emboli; in order for
      the reader to make a final screening decision. To test the efficacy of our
      system, we evaluated the change in performance of a newly certified retinal
      reader when grading a set of 40 color fundus images with and without the
      assistance of the software. The results demonstrated an improvement in reader's
      performance with the software assistance, in terms of accuracy of detection of
      vessel abnormalities, determination of retinopathy, and reading time. This system
      enables the reader in making computer-assisted vasculature assessment with high
      accuracy and consistency, at a reduced reading time. 

PMID- 25571443
TI  - An effective automated system for grading severity of retinal arteriovenous
      nicking in colour retinal images.
AB  - Retinal arteriovenous (AV) nicking is a precursor for hypertension, stroke and
      other cardiovascular diseases. In this paper, an effective method is proposed for
      the analysis of retinal venular widths to automatically classify the severity
      level of AV nicking. We use combination of intensity and edge information of the
      vein to compute its widths. The widths at various sections of the vein near the
      crossover point are then utilized to train a random forest classifier to classify
      the severity of AV nicking. We analyzed 47 color retinal images obtained from two
      population based studies for quantitative evaluation of the proposed method. We
      compare the detection accuracy of our method with a recently published four class
      AV nicking classification method. Our proposed method shows 64.51% classification
      accuracy in-contrast to the reported classification accuracy of 49.46% by the
      state of the art method. 

PMID- 25571444
TI  - RetinaCAD, a system for the assessment of retinal vascular changes.
AB  - This paper introduces RetinaCAD, a system, for the fast, reliable and automatic
      measurement of the Central Retinal Arteriolar Equivalent (CRAE), the Central
      Retinal Venular Equivalent (CRVE), and the Arteriolar-to-Venular Ratio (AVR)
      values, as well as several geometrical features of the retinal vasculature.
      RetinaCAD identifies important landmarks in the retina, such as the blood vessels
      and optic disc, and performs artery/vein classification and vessel width
      measurement. The estimation of the CRAE, CRVE and AVR values on 480 images from
      120 subjects has shown a significant correlation between right and left eyes and
      also between images of same eye acquired with different camera fields of view.
      AVR estimation in retinal images of 54 subjects showed the lowest values in
      people with diabetes or high blood pressure thus demonstrating the potential of
      the system as a CAD tool for early detection and follow-up of diabetes,
      hypertension or cardiovascular pathologies. 

PMID- 25571445
TI  - Super resolution for fundoscopy based on 3D image registration.
AB  - An approach to the generation of super-resolution (SR) images from fundoscopy
      images is proposed that is based on the 3D registration of the original
      fundoscopy images. The proposed approach utilizes a simple 3D registration method
      to enable the application of conventional SR techniques which, otherwise, employ
      2D image registration. Qualitative and quantitative comparative evaluation shows
      that the obtained results improve image definition and alleviate noise. 

PMID- 25571446
TI  - High-accuracy measurement of rotational eye movement by tracking of blood vessel
      images.
AB  - This study focuses on a technique for measuring the angle of rotational eye
      movement by tracking the conjunctival blood vessel ends of sclera, instead of
      grayscale iris patterns used in the existing techniques. It is because the blood
      vessel images of sclera have high grayscale contrasts. This technique especially
      recognizes the contour of the iris to detect the target conjunctival blood vessel
      end and use the degree of similarity by means of template matching to select
      automatically the blood vessel end to be tracked. The search region is limited by
      template matching to achieve low processing cost and high accuracy and resolution
      even when the background light varies. 

PMID- 25571447
TI  - Post-processing for spectral coherence of magnetoencephalogram background
      activity: application to Alzheimer's disease.
AB  - Estimating the connectivity between magnetoencephalogram (MEG) signals provides
      an excellent opportunity to analyze whole brain functional integration across a
      spectrum of conditions from health to disease. For this purpose, spectral
      coherence has been used widely as an easy-to-interpret metric of signal coupling.
      However, a number of systematic effects may influence the estimations of spectral
      coherence and subsequent inferences about brain activity. In this pilot study, we
      focus on the potentially confounding effects of the field spread and the on-going
      dynamic temporal variability inherent in the signals. We propose two simple post
      processing approaches to account for these: 1) a jack-knife procedure to account
      for the variance in the estimation of spectral coherence; and 2) a detrending
      technique to reduce its dependence on sensor proximity. We illustrate the effect
      of these techniques in the estimation of MEG spectral coherence in the alpha band
      for 36 patients with Alzheimer's disease and 26 control subjects. 

PMID- 25571448
TI  - Determination of seizure propagation across microdomains using spectral measures
      of causality.
AB  - The use of microelectrode arrays to measure electrical activity from the surface
      of the brain is increasingly being investigated as a means to improve seizure
      focus localization. In this work, we determine seizure propagation across
      microdomains sampled by such microelectrode arrays and compare the results using
      two widely used frequency domain measures of causality, namely the partial
      directed coherence and the directed direct transfer function. We show that these
      two measures produce very similar propagation patterns for simulated
      microelectrode activity over a relatively smaller number of channels. However as
      the number of channels increases, partial directed coherence produces better
      estimates of the actual propagation pattern. Additionally, we apply these two
      measures to determine seizure propagation over microelectrode arrays measured
      from a patient undergoing intracranial monitoring for seizure focus localization
      and find very similar patterns which also agree with a threshold based
      reconstruction during seizure onset. 

PMID- 25571449
TI  - Information dynamics in cardiorespiratory analyses: application to controlled
      breathing.
AB  - Voluntary adjustment of the breathing pattern is widely used to deal with stress
      related conditions. In this study, effects of slow and fast breathing with a low
      and high inspiratory to expiratory time on heart rate variability (HRV) are
      evaluated by means of information dynamics. Information transfer is quantified
      both as the traditional transfer entropy as well as the cross entropy, where the
      latter does not condition on the past of HRV, thereby taking the highly
      unidirectional relation between respiration and heart rate into account. The
      results show that the cross entropy is more suited to quantify cardiorespiratory
      information transfer as this measure increases during slow breathing, indicating
      the increased cardiorespiratory coupling and suggesting the shift towards vagal
      activation during slow breathing. Additionally we found that controlled
      breathing, either slow or fast, results as well in an increase in
      cardiorespiratory coupling, compared to spontaneous breathing, which demonstrates
      the beneficial effects of instructed breathing. 

PMID- 25571450
TI  - Investigating statistical differences in connectivity patterns properties at
      single subject level: a new resampling approach.
AB  - Methods based on the multivariate autoregressive (MVAR) approach are commonly
      used for effective connectivity estimation as they allow to include all available
      sources into a unique model. To ensure high levels of accuracy for high model
      dimensions, all the observations are used to provide a unique estimation of the
      model, and thus of the network and its properties. The unavailability of a
      distribution of connectivity values for a single experimental condition prevents
      to perform statistical comparisons between different conditions at a single
      subject level. This is a major limitation, especially when dealing with the
      heterogeneity of clinical conditions presented by patients. In the present paper
      we proposed a novel approach to the construction of a distribution of
      connectivity in a single subject case. The proposed approach is based on small
      perturbations of the networks properties and allows to assess significant changes
      in brain connectivity indexes derived from graph theory. Its feasibility and
      applicability were investigated by means of a simulation study and an application
      to real EEG data. 

PMID- 25571451
TI  - Directed neural connectivity changes in robot-assisted gait training: a partial
      Granger causality analysis.
AB  - Now-a-days robotic exoskeletons are often used to help in gait training of stroke
      patients. However, such robotic systems have so far yielded only mixed results in
      benefiting the clinical population. Therefore, there is a need to investigate how
      gait learning and de-learning get characterised in brain signals and thus
      determine neural substrate to focus attention on, possibly, through an
      appropriate brain-computer interface (BCI). To this end, this paper reports the
      analysis of EEG data acquired from six healthy individuals undergoing robot
      assisted gait training of a new gait pattern. Time-domain partial Granger
      causality (PGC) method was applied to estimate directed neural connectivity among
      relevant brain regions. To validate the results, a power spectral density (PSD)
      analysis was also performed. Results showed a strong causal interaction between
      lateral motor cortical areas. A frontoparietal connection was found in all robot
      assisted training sessions. Following training, a causal "top-down" cognitive
      control was evidenced, which may indicate plasticity in the connectivity in the
      respective brain regions. 

PMID- 25571452
TI  - Coherent source and connectivity analysis on simultaneously measured EEG and MEG
      data during isometric contraction.
AB  - The most well-known non-invasive electric and magnetic field measurement
      modalities are the electroencephalography (EEG) and magnetoencephalography (MEG).
      The first aim of the study was to implement the recently developed realistic head
      model which uses an integrative approach for both the modalities. The second aim
      of this study was to find the network of coherent sources and the modes of
      interactions within this network during isometric contraction (ISC) at (15-30 Hz)
      in healthy subjects. The third aim was to test the effective connectivity
      revealed by both the modalities analyzing them separately and combined. The Welch
      periodogram method was used to estimate the coherence spectrum between the EEG
      and the electromyography (EMG) signals followed by the realistic head modelling
      and source analysis method dynamic imaging of coherent sources (DICS) to find the
      network of coherent sources at the individual peak frequency within the beta band
      in healthy subjects. The last step was to identify the effective connectivity
      between the identified sources using the renormalized partial directed coherence
      method. The cortical and sub-cortical network comprised of the primary sensory
      motor cortex (PSMC), secondary motor area (SMA), and the cerebellum (C). The
      cortical and sub-cortical network responsible for the isometric contraction was
      similar in both the modalities when analysing them separately and combined. The
      SNR was not significantly different between the two modalities separately and
      combined. However, the coherence values were significantly higher in the combined
      modality in comparison to each of the modality separately. The effective
      connectivity analysis revealed plausible additional connections in the combined
      modality analysis. 

PMID- 25571453
TI  - Tracking instantaneous entropy in heartbeat dynamics through inhomogeneous point
      process nonlinear models.
AB  - Measures of entropy have been proved as powerful quantifiers of complex nonlinear
      systems, particularly when applied to stochastic series of heartbeat dynamics.
      Despite the remarkable achievements obtained through standard definitions of
      approximate and sample entropy, a time-varying definition of entropy
      characterizing the physiological dynamics at each moment in time is still
      missing. To this extent, we propose two novel measures of entropy based on the
      inho-mogeneous point-process theory. The RR interval series is modeled through
      probability density functions (pdfs) which characterize and predict the time
      until the next event occurs as a function of the past history. Laguerre
      expansions of the Wiener-Volterra autoregressive terms account for the long-term
      nonlinear information. As the proposed measures of entropy are instantaneously
      defined through such probability functions, the proposed indices are able to
      provide instantaneous tracking of autonomic nervous system complexity. Of note,
      the distance between the time-varying phase-space vectors is calculated through
      the Kolmogorov-Smirnov distance of two pdfs. Experimental results, obtained from
      the analysis of RR interval series extracted from ten healthy subjects during
      stand-up tasks, suggest that the proposed entropy indices provide instantaneous
      tracking of the heartbeat complexity, also allowing for the definition of
      complexity variability indices. 

PMID- 25571454
TI  - Low dimensional manifold embedding for scattering coefficients of intrapartum
      fetale heart rate variability.
AB  - Intrapartum fetal surveillance for early detection of fetal acidosis in clinical
      practice focuses on reducing neonatal morbidity via early detection. It is the
      subject of on going research studies attempting notably to improve detection
      performance by reducing false positive rate. In that context, the present
      contribution tailors to fetal heart rate variability analysis a graph-based
      dimensionality reduction procedure performed on scattering coefficients. Applied
      to a high quality and well-documented database constituted by obstetricians from
      a French academic hospital, the low dimensional embedding enables to distinguish
      between the temporal dynamics of healthy and acidotic fetuses, as well as to
      achieve satisfactory detection performance detection compared to those obtained
      by the clinical-benchmark FIGO criteria. 

PMID- 25571455
TI  - Advantages of signal-adaptive approaches for the nonlinear, time-variant analysis
      of heart rate variability of children with temporal lobe epilepsy.
AB  - Major aim of our study is to demonstrate that signal-adaptive approaches improve
      the nonlinear and time-variant analysis of heart rate variability (HRV) of
      children with temporal lobe epilepsy (TLE). Nonlinear HRV analyses are frequently
      applied in epileptic patients. As HRV is characterized by components with
      oscillatory properties frequency-selective methods are in the focus, whereby
      application of nonlinear analysis to linear filtered signals seems to be
      doubtful. Signal-adaptive methods that preserve nonlinear properties and utilize
      only the signal data for an automatic computation of the result could benefit to
      nonlinear analysis of HRV. Combinations of (1) the signal-adaptive Matched Gabor
      Transform with time-variant nonlinear bispectral analysis and of (2) signal
      adaptive Empirical Mode Decomposition methods with time-variant nonlinear
      stability analysis are investigated with regard to their application in the
      analysis of specific HRV components (respiratory sinus arrhythmia and Mayer wave
      associated low-frequency HRV components) of 18 children with TLE. Changes of
      timing and coordination of both HRV components during preictal, ictal and
      postictal periods occur which can be better quantified by advanced signal
      adaptive methods. Both approaches contribute with specific importance to the
      analysis. 

PMID- 25571457
TI  - Simultaneous Greedy Analysis Pursuit for compressive sensing of multi-channel ECG
      signals.
AB  - This paper addresses compressive sensing for multi-channel ECG. Compared to the
      traditional sparse signal recovery approach which decomposes the signal into the
      product of a dictionary and a sparse vector, the recently developed cosparse
      approach exploits sparsity of the product of an analysis matrix and the original
      signal. We apply the cosparse Greedy Analysis Pursuit (GAP) algorithm for
      compressive sensing of ECG signals. Moreover, to reduce processing time,
      classical signal-channel GAP is generalized to the multi-channel GAP algorithm,
      which simultaneously reconstructs multiple signals with similar support.
      Numerical experiments show that the proposed method outperforms the classical
      sparse multi-channel greedy algorithms in terms of accuracy and the single
      channel cosparse approach in terms of processing speed. 

PMID- 25571456
TI  - Assessing complexity of heart rate variability in people with spinal cord injury
      using local scale exponents.
AB  - Detrended fluctuation analysis (DFA) has been widely used to study dynamics of
      heart rate variability (HRV), which provides a quantitative parameter, the
      scaling exponent a, to represent the correlation properties of RR interval
      series. However, it has been demonstrated that HRV exhibits complex behavior that
      cannot be fully described by a single exponent. This study aimed to investigate
      whether local scale exponent alpha(t) with t being the time scale can reveal new
      features of HRV that cannot be reflected by DFA coefficients. To accurately
      estimate alpha(t), we developed an approach for correcting a(t) at small scales
      and verified the approach using simulated signals. We studied HRV in 12 subjects
      with spinal cord injury and 14 able-bodied controls during sitting and prone
      postures. The results showed that alpha(t) provides complementary views of HRV,
      suggesting that it may be used to evaluate the effects of SCI-induced autonomic
      damage on HRV. 

PMID- 25571458
TI  - Multi-parametric heart rate analysis in premature babies exposed to sudden infant
      death syndrome.
AB  - Severe premature babies present a risk profile higher than the normal population.
      Reasons are related to the incomplete development of physiological systems that
      support baby's life. Heart Rate Variability (HRV) analysis can help the
      identification of distress conditions as it is sensitive to Autonomic Nervous
      System (ANS) behavior. This paper presents results obtained in 35 babies with
      severe prematurity, in quiet and active sleep and in prone and supine position.
      HRV was analyzed in time and frequency domain and with nonlinear parameters. The
      novelty of this approach lies in the combined use of parameters generally adopted
      in fetal monitoring and "adult" indices. Results show that most parameters
      succeed in classifying different experimental conditions. This is very promising
      as our final objective is to identify a set of parameters that could be the basis
      for a risk classifier to improve the care path of premature population. 

PMID- 25571459
TI  - Comparison of a priori calibration models for respiratory inductance
      plethysmography during running.
AB  - Respiratory inductive plethysmography (RIP) has been introduced as an alternative
      for measuring ventilation by means of body surface displacement (diameter changes
      in rib cage and abdomen). Using a posteriori calibration, it has been shown that
      RIP may provide accurate measurements for ventilatory tidal volume under exercise
      conditions. Methods for a priori calibration would facilitate the application of
      RIP. Currently, to the best knowledge of the authors, none of the existing
      ambulant procedures for RIP calibration can be used a priori for valid subsequent
      measurements of ventilatory volume under exercise conditions. The purpose of this
      study is to develop and validate a priori calibration algorithms for ambulant
      application of RIP data recorded in running exercise. We calculated Volume Motion
      Coefficients (VMCs) using seven different models on resting data and compared the
      root mean squared error (RMSE) of each model applied on running data. Least
      squares approximation (LSQ) without offset of a two-degree-of-freedom model
      achieved the lowest RMSE value. In this work, we showed that a priori calibration
      of RIP exercise data is possible using VMCs calculated from 5 min resting phase
      where RIP and flowmeter measurements were performed simultaneously. The results
      demonstrate that RIP has the potential for usage in ambulant applications. 

PMID- 25571460
TI  - A new Mercer sigmoid kernel for clinical data classification.
AB  - In classification with Support Vector Machines, only Mercer kernels, i.e. valid
      kernels, such as the Gaussian RBF kernel, are widely accepted and thus suitable
      for clinical data. Practitioners would also like to use the sigmoid kernel, a non
      Mercer kernel, but its range of validity is difficult to determine, and even
      within range its validity is in dispute. Despite these shortcomings the sigmoid
      kernel is used by some, and two kernels in the literature attempt to emulate and
      improve upon it. We propose the first Mercer sigmoid kernel, that is therefore
      trustworthy for the classification of clinical data. We show the similarity
      between the Mercer sigmoid kernel and the sigmoid kernel and, in the process,
      identify a normalization technique that improves the classification accuracy of
      the latter. The Mercer sigmoid kernel achieves the best mean accuracy on three
      clinical data sets, detecting melanoma in skin lesions better than the most
      popular kernels; while with non-clinical data sets it has no significant
      difference in median accuracy as compared with the Gaussian RBF kernel. It
      consistently classifies some points correctly that the Gaussian RBF kernel does
      not and vice versa. 

PMID- 25571461
TI  - Automatic stress-relieving music recommendation system based on
      photoplethysmography-derived heart rate variability analysis.
AB  - This paper presents an automatic stress-relieving music recommendation system
      (ASMRS) for individual music listeners. The ASMRS uses a portable, wireless
      photoplethysmography module with a finger-type sensor, and a program that
      translates heartbeat signals from the sensor to the stress index. The
      sympathovagal balance index (SVI) was calculated from heart rate variability to
      assess the user's stress levels while listening to music. Twenty-two healthy
      volunteers participated in the experiment. The results have shown that the
      participants' SVI values are highly correlated with their prespecified music
      preferences. The sensitivity and specificity of the favorable music
      classification also improved as the number of music repetitions increased to 20
      times. Based on the SVI values, the system automatically recommends favorable
      music lists to relieve stress for individuals. 

PMID- 25571462
TI  - Blood glucose prediction by breath analysis system with feature selection and
      model fusion.
AB  - It has been shown that the concentration of acetone in breath is correlated with
      the subject's blood glucose level (BGL). Therefore, noninvasive BGL monitoring of
      diabetics can be achieved by the analysis of components in breath. In this paper,
      a breath analysis device with 10 gas sensors is designed to measure breath
      samples. Transient features are extracted from the signals of the sensors.
      Sequential forward selection is applied on the features to find the most
      informative ones. In order to reduce the interference brought by the inter
      subject variance of breath acetone, global and local BGL prediction models are
      built and fused. The two models are based on different training strategies and
      have different advantages. Experiments were conducted using 203 breath samples
      from 36 diabetic subjects. Results show that the accuracy of the proposed feature
      is better than other similar features and the model fusion strategy is effective.
      The mean absolute error and mean relative absolute error of the system are 2.07
      mmol/L and 20.69%, respectively. 

PMID- 25571463
TI  - Foot gait time series estimation based on support vector machine.
AB  - A new algorithm for the estimation of stride interval time series from foot gait
      signals is proposed. The algorithm is based on the detection of beginning of heel
      strikes in the signal by using the support vector machine. Morphological
      operations are used to enhance the accuracy of detection. By taking backward
      differences of the detected beginning of heel strikes, stride interval time
      series is estimated. Simulation results are presented which shows that the
      proposed algorithm yields fairly accurate estimation of stride interval time
      series where estimation error for mean and standard deviation of the time series
      is of the order of 10(-4). 

PMID- 25571464
TI  - Gesture recognition for smart home applications using portable radar sensors.
AB  - In this article, we consider the design of a human gesture recognition system
      based on pattern recognition of signatures from a portable smart radar sensor.
      Powered by AAA batteries, the smart radar sensor operates in the 2.4 GHz
      industrial, scientific and medical (ISM) band. We analyzed the feature space
      using principle components and application-specific time and frequency domain
      features extracted from radar signals for two different sets of gestures. We
      illustrate that a nearest neighbor based classifier can achieve greater than 95%
      accuracy for multi class classification using 10 fold cross validation when
      features are extracted based on magnitude differences and Doppler shifts as
      compared to features extracted through orthogonal transformations. The reported
      results illustrate the potential of intelligent radars integrated with a pattern
      recognition system for high accuracy smart home and health monitoring purposes. 

PMID- 25571465
TI  - Correlating 2D histological slice with 3D MRI image volume using smart phone as
      an interactive tool for muscle study.
AB  - In muscle dystrophy studies, registration of histological image with MRI image
      volume enables cross validation of MRI biomarkers using pathological result.
      However, correlation of 2D histology slice with 3D MRI volume is technically
      challenging due to the potentially non-orthogonal slice plane and incomplete or
      distorted histological slice. This paper presents an efficient method to directly
      perform the 2D-3D registration. The method is unique in that it uses smart phone
      as a navigation tool for initial alignment followed by an overlap invariant
      mutual information-based refinement. Experimental results using animal muscle
      samples images from a 3T MRI and HE stained histological images show that the
      proposed method is capable of aligning the histological slice with an oblique
      slice in MR volume. 

PMID- 25571466
TI  - Field-inhomogeneity-corrected low-rank filtering of magnetic resonance
      spectroscopic imaging data.
AB  - Low signal-to-noise ratio has been a major problem in magnetic resonance
      spectroscopic imaging (MRSI). A low-rank approximation based denoising method has
      been recently proposed to address this problem by exploiting the partial
      separability properties of MRSI data. However, field inhomogeneity, an
      unavoidable complication in practice, can violate the partial separability
      assumption and thus degrade the denoising performance of the low-rank filtering
      method. This paper presents a field-inhomogeneity-corrected low-rank filtering
      method to achieve more robust denoising of practical MRSI data. In vivo
      experiment results have been used to demonstrate the effectiveness of the
      proposed method. 

PMID- 25571467
TI  - A unified machine learning method for task-related and resting state fMRI data
      analysis.
AB  - Functional magnetic resonance imaging (fMRI) aims to localize task-related brain
      activation or resting-state functional connectivity. Most existing fMRI data
      analysis techniques rely on fixed thresholds to identify active voxels under a
      task condition or functionally connected voxels in the resting state. Due to fMRI
      non-stationarity, a fixed threshold cannot adapt to intra- and inter-subject
      variation and provide a reliable mapping of brain function. In this work, a
      machine learning method is proposed for a unified analysis of both task-related
      and resting state fMRI data. Specifically, the mapping of brain function in a
      task condition or resting state is formulated as an outlier detection process.
      Support vector machines are used to provide an initial mapping and refine mapping
      results. The method does not require a fixed threshold for the final decision,
      and can adapt to fMRI non-stationarity. The proposed method was evaluated using
      experimental data acquired from multiple human subjects. The results indicate
      that the proposed method can provide reliable mapping of brain function, and is
      applicable to various quantitative fMRI studies. 

PMID- 25571468
TI  - Normalized left ventricular workload using phase-contrast magnetic resonance
      imaging in patients with aortic stenosis.
AB  - Aortic stenosis (AS) severity contributes to the left ventricle (LV)
      deterioration due to the aortic valve narrowing and the alteration of systemic
      hemodynamic load. This load increment may also increase the LV stroke work (SW)
      which represent the required energy to deliver the blood at ejection. In this
      study, SW was derived from in-vivo cardiovascular magnetic resonance (CMR)
      velocity measurements (n=57) using a lumped-parametric model. Furthermore,
      normalized SW (N-SW) was evaluated as AS severity parameter. SW differentiated
      from normal flow (>35 mL/m(2)) and low flow (<35 mL/m(2)) states (p<0.05). N-SW
      showed a good association with valve effective orifice area (EOA, r=-0.5,
      p<0.001) and valvulo-arterial impedance (ZVA, r=0.65, p<0.001). A severity
      threshold for N-SW (1.5 cJ/mL) was found using an EOA=1 cm(2) as AS severity
      marker. CMR-derived SW and N-SW may be useful to the assessment and grading of AS
      patients.

PMID- 25571469
TI  - Enhancing the convex analysis of mixtures technique for estimating DCE-MRI
      pharmacokinetic parameters.
AB  - Dynamic-contrast enhanced magnetic resonance imaging (DCE-MRI) is a useful
      noninvasive tool for monitoring tumor angiogenesis and assessing therapeutic
      response. One major problem that prevents an accurate estimation of
      pharmacokinetic parameters is partial-volume effect (PVE). A multi-tissue
      compartmental modeling (CM) technique supported by convex analysis of mixtures
      (CAM) is used to overcome the PVE by clustering pixels and constructing a simplex
      whose vertices are of a single compartment type. CAM uses the identified pure
      volume pixels to estimate the kinetics of the tissues under investigation. This
      paper reports an enhanced version of CAM-CM to identify pure-volume pixels more
      accurately. This includes the consideration of the neighborhood effect on each
      pixel and the use of a barycentric coordinate system to identify more pure-volume
      pixels and to test those identified by CAM. The enhanced CAM achieved root mean
      square error (RMSE) of 0.00348 +/- 0.000019, lower than the RMSE of 0.05409 +/-
      0.00496 achieved by CAM. 

PMID- 25571470
TI  - Total variation based edge enhancement for level set segmentation and asymmetry
      analysis in breast thermograms.
AB  - In this work, an attempt has been made to perform asymmetry analysis in breast
      thermograms using non-linear total variation diffusion filter and reaction
      diffusion based level set method. Breast images used in this study are obtained
      from online database of the project PROENG. Initially the images are subjected to
      total variation (TV) diffusion filter to generate the edge map. Reaction
      diffusion based level set method is employed to segment the breast tissues using
      TV edge map as stopping boundary function. Asymmetry analysis is performed on the
      segmented breast tissues using wavelet based structural texture features. The
      results show that nonlinear total variation based reaction diffusion level set
      method could efficiently segment the breast tissues. This method yields high
      correlation between the segmented output and the ground truth than the
      conventional level set. Structural texture features extracted from the wavelet
      coefficients are found to be significant in demarcating normal and abnormal
      tissues. Hence, it appears that the asymmetry analysis on segmented breast
      tissues extracted using total variation edge map can be used efficiently to
      identify the pathological conditions of breast thermograms. 

PMID- 25571471
TI  - Diagnosis of prostatic carcinoma on multiparametric magnetic resonance imaging
      using shearlet transform.
AB  - This paper presents a method to diagnose prostate cancer on multiparametric
      magnetic resonance imaging (Mp-MRI) using the shearlet transform. The objective
      is classification of benign and malignant regions on transverse relaxation time
      weighted (T2W), dynamic contrast enhanced (DCE), and apparent diffusion
      coefficient (ADC) images. Compared with conventional wavelet filters, shearlet
      has inherent directional sensitivity, which makes it suitable for characterizing
      small contours of cancer cells. By applying a multi-scale decomposition, the
      shearlet transform captures visual information provided by edges detected at
      different orientations and multiple scales in each region of interest (ROI) of
      the images. ROIs are represented by histograms of shearlet coefficients (HSC) and
      then used as features in Support Vector Machines (SVM) to classify ROIs as benign
      or malignant. Experimental results show that our method can recognize carcinoma
      in T2W, DCE, and ADC with overall sensitivity of 92%, 100%, and 89%,
      respectively. Hence, application of shearlet transform may further increase
      utility of Mp-MRI for prostate cancer diagnosis. 

PMID- 25571472
TI  - Semantic interpretation of robust imaging features for Fuhrman grading of renal
      carcinoma.
AB  - Pattern recognition in tissue biopsy images can assist in clinical diagnosis and
      identify relevant image characteristics linked with various biological
      characteristics. Although previous work suggests several informative imaging
      features for pattern recognition, there exists a semantic gap between
      characteristics of these features and pathologists' interpretation of
      histopathological images. To address this challenge, we develop a clinical
      decision support system for automated Fuhrman grading of renal carcinoma biopsy
      images. We extract 1316 color, shape, texture and topology features and develop
      one vs. all models for four Fuhrman grades. Our models are highly accurate with
      90.4% accuracy in a four-class prediction. Predictivity analysis suggests good
      generalization of the model development methodology through robustness to dataset
      sampling in cross-validation. We provide a semantic interpretation for the
      imaging features used in these models by linking features to pathologists'
      grading criteria. Our study identifies novel imaging features that are
      semantically linked to Fuhrman grading criteria. 

PMID- 25571473
TI  - Tumor segmentation with multi-modality image in Conditional Random Field
      framework with logistic regression models.
AB  - We have developed a semi-automatic method for multi-modality image segmentation
      aimed at reducing the manual process time via machine learning while preserving
      human guidance. Rather than reliance on heuristics, human oversight and expert
      training from images is incorporated into logistic regression models. The latter
      serve to estimate the probability of tissue class assignment for each voxel as
      well as the probability of tissue boundary occurring between neighboring voxels
      given the multi-modal image intensities. The regression models provide parameters
      for a Conditional Random Field (CRF) framework that defines an energy function
      with the regional and boundary probabilistic terms. Using this CRF, a max
      flow/min-cut algorithm is used to segment other slices in the 3D image set
      automatically with options of addition user input. We apply this approach to
      segment visible tumors in multi-modal medical volumetric images. 

PMID- 25571474
TI  - Enhanced classification of malignant melanoma lesions via the integration of
      physiological features from dermatological photographs.
AB  - Traditional methods for early detection of melanoma rely upon a dermatologist to
      visually assess a skin lesion using the ABCDE (Asymmetry, Border irregularity,
      Color variegation, Diameter, Evolution) criteria before confirmation can be done
      through biopsy by a pathologist. However, this visual assessment strategy taken
      by dermatologists is hampered by clinician subjectivity and suffers from low
      sensitivity. Computer-aided diagnostic methods based on dermatological
      photographs are being developed to aid in the melanoma diagnosis process, but
      most of these methods rely only on superficial, topographic features that can be
      limiting in characterizing melanoma. In this work, a hybrid feature model is
      introduced for characterizing skin lesions that combines low-level and high-level
      features, and augments them with a set of physiological features extracted from
      dermatological photographs using a nearest-neighbor nonlinear model to improve
      classification performance. The physiological features extracted from the lesion
      for the proposed hybrid feature model include those based on: i) eumelanin
      concentrations, ii) pheomelanin concentrations, and iii) blood oxygen saturation.
      The proposed hybrid feature model was evaluated on 206 dermatological photographs
      of skin lesions (119 confirmed melanoma cases, 87 confirmed non-melanoma cases)
      using a cross validation scheme. The experimental results show that the proposed
      hybrid feature model, with integrated physiological features, provided improved
      sensitivity, specificity, precision and accuracy for the purpose of melanoma
      classification. 

PMID- 25571476
TI  - Hierarchical and binary spatial descriptors for lung nodule image retrieval.
AB  - With the increasing amount of image data available for cancer staging and
      diagnosis, it is clear that content-based image retrieval techniques are becoming
      more important to assist physicians in making diagnoses and tracking disease.
      Domain-specific feature descriptors have been previously shown to be effective in
      the retrieval of lung tumors. This work proposes a method to improve the rotation
      invariance of the hierarchical spatial descriptor, as well as presents a new
      binary descriptor for the retrieval of lung nodule images. The descriptors were
      evaluated on the ELCAP public access database, exhibiting good performance
      overall. 

PMID- 25571475
TI  - Determination of border irregularity in dermoscopic color images of pigmented
      skin lesions.
AB  - Malignant melanoma, which is the most dangerous type of skin cancer, is commonly
      diagnosed in all people, regardless of age, gender, or race. In the last several
      years an increasing melanoma incidence and mortality rate has been observed
      worldwide. In this research we present a new approach to the detection and
      classification of border irregularity, one of the major parameter in a widely
      used diagnostic algorithm ABCD rule of dermoscopy. Accurate assessment of
      irregular borders is clinically important due to a significantly different
      occurrence in benign and malignant skin lesions. In this paper we describe a
      complex algorithm containing following steps: image enhancement, lesion
      segmentation, border irregularity detection as well as classification. The
      algorithm has been tested on 300 dermoscopic images and achieved a detection of
      79% and classification accuracy of 90%. Compared to state-of-the-art, we obtain
      improved classification accuracy. 

PMID- 25571478
TI  - Simultaneous stimulation and recording of cardiac depolarization enabled by high
      frequency stimulation.
AB  - High-frequency stimulation techniques have been recently proposed for the pacing
      and control of excitability of cardiac tissues. This paper introduces a system
      designed specifically for such stimulation, and demonstrates the unique ability
      to record depolarization events on the same electrode used for stimulation,
      during the stimulus. Experimental results with HL-1 cardiomyocytes are presented,
      highlighting key concepts enabled by this system, such as direct strength
      duration relationship measurement and beat-to-beat stimulation threshold
      monitoring following pacing onset or pharmacological modulation. 

PMID- 25571479
TI  - Assessing real-time RR-QT frequency-domain measures of coupling and causality
      through inhomogeneous point-process bivariate models.
AB  - Ventricular repolarization instability is known to be related to arrhythmogenesis
      and increased risk of sudden cardiac death. These repolarization dynamics are
      linked to the distance between T-wave and Q-wave occurrences (QT) on the ECG, and
      they are coupled with R-wave to R-wave interval variability (RRV). Several
      efforts have been dedicated to the analysis of QT-RR interactions in order to
      provide both a quantification of the coupling and estimates of intrinsic
      repolarization dynamics. However, a methodology able to quantify dynamic changes
      in repolarization variability unrelated to RRV dynamics is still needed. In this
      study, we propose a bivariate model embedded within a multiple inhomogeneous
      point-process framework to obtain time-varying tracking of (causal) interactions
      between QT variability (QTV), a marker of repolarization variability, and RRV.
      Data from 15 healthy subjects undergoing a tilt table test were analyzed. Our
      results demonstrate that the model effectively captures the time-varying mutual
      QTV-RRV interactions. The analysis of time-varying coherence confirms that head
      up tilt is associated with a decrease in linear QTV-RRV coupling, while time
      varying directed coherence shows that intrinsic QTV becomes more prominent during
      head-up tilt.

PMID- 25571477
TI  - A structural framework for interpretation of four-electrode microimpedance
      spectra in cardiac tissue.
AB  - Renewed interest in the four-electrode method for identification of passive
      electrical properties in cardiac tissue has been sparked by a recognition that
      measurements made with sensors in close proximity are frequency dependent.
      Therefore, resolution of four-electrode microimpedance spectra (4EMS) may provide
      an opportunity for routine identification of passive electrical properties for
      the interstitial and intracellular compartments using only interstitial access.
      The present study documents a structural framework in which the tissue
      resistivity (rhot) and reactivity (xt) that comprise spectra are computed using
      interstitial and intracellular microimpedance distributions that account for
      differences in compartment size, anisotropic electrical properties in each
      compartment and electrode separations. We used this framework to consider 4EMS
      development with relatively wide (d=1 mm) and fine (d=250 MUm) electrode
      separations and sensors oriented along myocyte axes, across myocyte axes and
      intermediate between those axes. 

PMID- 25571480
TI  - ETD: an extended time delay algorithm for ventricular fibrillation detection.
AB  - Ventricular fibrillation (VF) is the most serious type of heart attack which
      requires quick detection and first aid to improve patients' survival rates. To be
      most effective in using wearable devices for VF detection, it is vital that the
      detection algorithms be accurate, robust, reliable and computationally efficient.
      Previous studies and our experiments both indicate that the time-delay (TD)
      algorithm has a high reliability for separating sinus rhythm (SR) from VF and is
      resistant to variable factors, such as window size and filtering method. However,
      it fails to detect some VF cases. In this paper, we propose an extended time
      delay (ETD) algorithm for VF detection and conduct experiments comparing the
      performance of ETD against five good VF detection algorithms, including TD, using
      the popular Creighton University (CU) database. Our study shows that (1) TD and
      ETD outperform the other four algorithms considered and (2) with the same
      sensitivity setting, ETD improves upon TD in three other quality measures for up
      to 7.64% and in terms of aggregate accuracy, the ETD algorithm shows an
      improvement of 2.6% of the area under curve (AUC) compared to TD. 

PMID- 25571481
TI  - Limitations of animal electrical cardiac safety models.
AB  - INTRODUCTION: Human electrical safety standards are based almost exclusively on
      animal studies and there is an unjustified assumption that ventricular
      fibrillation (VF) thresholds in animals are the same as those in humans. METHODS
      AND RESULTS: We analyzed differences between animals and humans in cardiac
      stimulation. A broad literature survey revealed that swine are a fragile
      electrophysiologic research species and have a dense intramural Purkinje fiber
      network, which is not found in some other species, including humans. Anesthesia
      agents have to be chosen carefully as swine are prone to malignant hyperthermia.
      Cardiac stimulation thresholds depend on weight and capture rates. Thus, the
      animal weight has to be representative of the weight of human subjects. Studies
      have shown significant ECG differences between humans and other species,
      including swine and canine. At least one study suggested that rabbit hearts tend
      to develop VF in a manner more similar to that seen in humans. CONCLUSION: Animal
      studies can play a role in conservatively evaluating cardiac safety. However,
      while still abiding by the precautionary principle, animal study design has to
      take into account the significant anatomical and electrophysiological differences
      between humans and other mammals. Data from multiple animal models may offer
      broader perspectives. If attempts are made to extrapolate animal results to
      humans then appropriate numerical correction factors should be applied, such as
      some of those discussed in this article.

PMID- 25571482
TI  - ICD lead failure detection through high frequency impedance.
AB  - Abrasion-induced insulation breach is a common failure mode of silicone-body,
      transvenous, implantable cardioverter defibrillator leads. It is caused either by
      external compression or internal motion of conducting cables. The present method
      of monitoring lead integrity measures low frequency conductor impedance. It
      cannot detect insulation failures until both the silicone lead body and inner
      fluoropolymer insulation have been breached completely, exposing conductors
      directly to blood or tissue. Thus the first clinical presentation may be either
      failure to deliver a life-saving shock or painful, inappropriate shocks in normal
      rhythm. We present a new method for identifying lead failure based on high
      frequency impedance measurements. This method was evaluated in 3D electromagnetic
      simulation and bench testing to identify insulation defects in the St. Jude
      Medical Riata(r) lead, which is prone to insulation breach. 

PMID- 25571483
TI  - High-performance brain-machine interface enabled by an adaptive optimal feedback
      controlled point process decoder.
AB  - Brain-machine interface (BMI) performance has been improved using Kalman filters
      (KF) combined with closed-loop decoder adaptation (CLDA). CLDA fits the decoder
      parameters during closed-loop BMI operation based on the neural activity and
      inferred user velocity intention. These advances have resulted in the recent
      ReFIT-KF and SmoothBatch-KF decoders. Here we demonstrate high-performance and
      robust BMI control using a novel closed-loop BMI architecture termed adaptive
      optimal feedback-controlled (OFC) point process filter (PPF). Adaptive OFC-PPF
      allows subjects to issue neural commands and receive feedback with every spike
      event and hence at a faster rate than the KF. Moreover, it adapts the decoder
      parameters with every spike event in contrast to current CLDA techniques that do
      so on the time-scale of minutes. Finally, unlike current methods that rotate the
      decoded velocity vector, adaptive OFC-PPF constructs an infinite-horizon OFC
      model of the brain to infer velocity intention during adaptation. Preliminary
      data collected in a monkey suggests that adaptive OFC-PPF improves BMI control.
      OFC-PPF outperformed SmoothBatch-KF in a self-paced center-out movement task with
      8 targets. This improvement was due to both the PPF's increased rate of control
      and feedback compared with the KF, and to the OFC model suggesting that the OFC
      better approximates the user's strategy. Also, the spike-by-spike adaptation
      resulted in faster performance convergence compared to current techniques. Thus
      adaptive OFC-PPF enabled proficient BMI control in this monkey. 

PMID- 25571484
TI  - Addressing low frequency movement artifacts in EEG signal recorded during center
      out reaching tasks.
AB  - The successful application of noninvasive brain-computer interfaces (BCI) to
      neurological rehabilitation requires examination of low frequency movement
      artifacts and development of accurate new methods for their correction. To this
      end, this study applies an adaptive trend extraction method to
      electroencephalogram (EEG) signals recorded during active and passive center-out
      reaching tasks. Distinct patterns are discovered, which correlate to arm
      kinematics, but are shown to be largely artifactual in nature. Notably, these
      patterns are found to be similar to features currently used for discrimination of
      movement direction, indicating a necessity for caution and precise signal
      processing methods when utilizing low frequency content of EEG signals in such
      applications. 

PMID- 25571485
TI  - Subject-to-subject adaptation to reduce calibration time in motor imagery-based
      brain-computer interface.
AB  - In order to enhance the usability of a motor imagery-based brain-computer
      interface (BCI), it is highly desirable to reduce the calibration time. Due to
      inter-subject variability, typically a new subject has to undergo a 20-30 minutes
      calibration session to collect sufficient data for training a BCI model based on
      his/her brain patterns. This paper proposes a new subject-to-subject adaptation
      algorithm to reliably reduce the calibration time of a new subject to only 3-4
      minutes. To reduce the calibration time, unlike several past studies, the
      proposed algorithm does not require a large pool of historic sessions. In the
      proposed algorithm, using only a few trials from the new subject, first, the new
      subject's data is adapted to each available historic session separately. This is
      done by a linear transformation minimizing the distribution difference between
      the two groups of EEG data. Thereafter, among the available historic sessions,
      the one matched the most to the new subject's adapted data is selected as the
      calibration session. Consequently, the previously trained model based on the
      selected historic session is entirely used for the classification of the new
      subject's data after adaptation. The proposed algorithm is evaluated on a
      publicly available dataset with 9 subjects. For each subject, the calibration
      session is selected only from the calibration sessions of the eight other
      subjects. The experimental results showed that our proposed algorithm not only
      reduced the calibration time by 85%, but also performed on average only 1.7% less
      accurate than the subject-dependent calibration results. 

PMID- 25571486
TI  - Object discrimination using optimized multi-frequency auditory cross-modal haptic
      feedback.
AB  - As the field of brain-machine interfaces and neuro-prosthetics continues to grow,
      there is a high need for sensor and actuation mechanisms that can provide haptic
      feedback to the user. Current technologies employ expensive, invasive and often
      inefficient force feedback methods, resulting in an unrealistic solution for
      individuals who rely on these devices. This paper responds through the
      development, integration and analysis of a novel feedback architecture where
      haptic information during the neural control of a prosthetic hand is perceived
      through multi-frequency auditory signals. Through representing force magnitude
      with volume and force location with frequency, the feedback architecture can
      translate the haptic experiences of a robotic end effector into the alternative
      sensory modality of sound. Previous research with the proposed cross-modal
      feedback method confirmed its learnability, so the current work aimed to
      investigate which frequency map (i.e. frequency-specific locations on the hand)
      is optimal in helping users distinguish between hand-held objects and tasks
      associated with them. After short use with the cross-modal feedback during the
      electromyographic (EMG) control of a prosthetic hand, testing results show that
      users are able to use audial feedback alone to discriminate between everyday
      objects. While users showed adaptation to three different frequency maps, the
      simplest map containing only two frequencies was found to be the most useful in
      discriminating between objects. This outcome provides support for the feasibility
      and practicality of the cross-modal feedback method during the neural control of
      prosthetics. 

PMID- 25571487
TI  - Classification of hand movement direction based on EEG high-gamma activity.
AB  - The Electroencephalogram (EEG) is a non-invasive technique used in the medical
      field to record and analyze brain activity. In particular, Brain Machine
      Interfaces (BMI) create this bridge between brain signals and the external world
      through prosthesis, visual interfaces and other physical devices. This paper
      investigates the relation between particular hand movement directions while using
      a BMI and the EEG recordings during such movement. The Common Spatial Pattern
      method (CSP) over the high-gamma frequency band is utilized in order to
      discriminate opposite hand movement directions. The experiment is performed with
      three subjects and the average classification accuracy is obtained for two
      different cases. 

PMID- 25571488
TI  - Decoding the non-stationary neuron spike trains by dual Monte Carlo point process
      estimation in motor Brain Machine Interfaces.
AB  - Decoding algorithm in motor Brain Machine Interfaces translates the neural
      signals to movement parameters. They usually assume the connection between the
      neural firings and movements to be stationary, which is not true according to the
      recent studies that observe the time-varying neuron tuning property. This
      property results from the neural plasticity and motor learning etc., which leads
      to the degeneration of the decoding performance when the model is fixed. To track
      the non-stationary neuron tuning during decoding, we propose a dual model
      approach based on Monte Carlo point process filtering method that enables the
      estimation also on the dynamic tuning parameters. When applied on both simulated
      neural signal and in vivo BMI data, the proposed adaptive method performs better
      than the one with static tuning parameters, which raises a promising way to
      design a long-term-performing model for Brain Machine Interfaces decoder. 

PMID- 25571490
TI  - Control of the coupled motion of a 6 DoF robotic arm and a continuum manipulator
      for the treatment of pelvis osteolysis.
AB  - The paper addresses the coupled motion of a 6 degree of freedom robot and a snake
      like dexterous manipulator (SDM) designed for the treatment of bone defects
      behind the implant during total hip arthroplasty revision surgery. We have
      formulated the problem as a weighted, multi-objective constraint, linear
      optimization. A remote center of motion (RCM) acts as a virtual constraint for
      the robot. The coupled robot kinematics does not assume piecewise-constant
      curvature for the SDM. We have evaluated our method by simulating the coupled
      system inside a potential lesion area. 

PMID- 25571489
TI  - Endoscopic add-on stiffness probe for real-time soft surface characterisation in
      MIS.
AB  - This paper explores a novel stiffness sensor which is mounted on the tip of a
      laparoscopic camera. The proposed device is able to compute stiffness when
      interacting with soft surfaces. The sensor can be used in Minimally Invasive
      Surgery, for instance, to localise tumor tissue which commonly has a higher
      stiffness when compared to healthy tissue. The purely mechanical sensor structure
      utilizes the functionality of an endoscopic camera to the maximum by visually
      analyzing the behavior of trackers within the field of view. Two pairs of spheres
      (used as easily identifiable features in the camera images) are connected to two
      springs with known but different spring constants. Four individual indenters
      attached to the spheres are used to palpate the surface. During palpation, the
      spheres move linearly towards the objective lens (i.e. the distance between lens
      and spheres is changing) resulting in variations of their diameters in the camera
      images. Relating the measured diameters to the different spring constants, a
      developed mathematical model is able to determine the surface stiffness in real
      time. Tests were performed using a surgical endoscope to palpate silicon phantoms
      presenting different stiffness. Results show that the accuracy of the sensing
      system developed increases with the softness of the examined tissue. 

PMID- 25571491
TI  - A force-controlled robotic micromanipulation system for mechanotransduction
      studies of Drosophila larvae.
AB  - This paper presents an automated robotic micromanipulation system capable of
      force-controlled mechanical stimulation and fluorescence imaging of Drosophila
      larvae, for mechanotransduction studies of Drosophila neural circuitry. An
      elastomeric microdevice is developed for efficient immobilization of an array of
      larvae for subsequent force-controlled touching. A microelectromechanical systems
      (MEMS) based force sensor is integrated into the system for closed-loop force
      control of larva touching at a resolution of 50 MUN. Two microrobots are
      coordinately servoed using orchestrated position and force control laws for
      automatic operations. The system performs simultaneous force-controlled larva
      touching and fluorescence imaging at a speed of 4 larvae per minute, with a
      success rate of 92.5%. This robotic system will greatly facilitate the dissection
      of mechanotransduction mechanisms of Drosophila larvae at both the molecular and
      cellular levels. 

PMID- 25571492
TI  - Hyper- and viscoelastic modeling of needle and brain tissue interaction.
AB  - Deep needle insertion into brain is important for both diagnostic and therapeutic
      clinical interventions. We have developed an automated system for robotically
      steering flexible needles within the brain to improve targeting accuracy. In this
      work, we have developed a finite element needle-tissue interaction model that
      allows for the investigation of safe parameters for needle steering. The tissue
      model implemented contains both hyperelastic and viscoelastic properties to
      simulate the instantaneous and time-dependent responses of brain tissue. Several
      needle models were developed with varying parameters to study the effects of the
      parameters on tissue stress, strain and strain rate during needle insertion and
      rotation. The parameters varied include needle radius, bevel angle, bevel tip
      fillet radius, insertion speed, and rotation speed. The results will guide the
      design of safe needle tips and control systems for intracerebral needle steering.

PMID- 25571493
TI  - Electromagnetic tracking performance analysis and optimization.
AB  - PURPOSE: The purpose of this study is to evaluate the uncertainties of an
      electromagnetic (EM) tracking system and to improve both the trueness and the
      precision of the EM tracker. METHODS: For evaluating errors, we introduce an
      optical (OP) tracking system and consider its measurement as "ground truth". In
      the experiment, static data sets and dynamic profiles are collected in both
      relatively less-metallic environments. Static data sets are for error modeling,
      and dynamic ones are for testing. To improve the trueness and precision of the EM
      tracker, tracker calibration based on polynomial fitting and smooth filters, such
      as the Kalman filter, the moving average filter and the local regression filter,
      are deployed. RESULTS: From the experimental data analysis, as the distance
      between the transmitter and the sensor of the EM tracking system increases, the
      trueness and precision tend to decrease. The system's trueness and jitter errors
      can be modeled as the 3(rd) order polynomial error equations. After minimizing
      the positional error and applying smoothing filters, the mean value of error
      reduction is 36.9%. CONCLUSION: Our method can effectively reduce both positional
      systematic error and jitter error caused by EM field distortion. The method is
      successfully applied to calibrate an EM tracked surgical cautery tool.

PMID- 25571494
TI  - Dominant component in muscle fatigue induced hand tremor during laparoscopic
      surgical manipulation.
AB  - Accuracy of laparoscopic surgery gets affected by the hand tremor of the
      surgeons. Though cognitive load is inevitable in such activity which promotes
      tremor, muscle fatigue induced tremor is significant among the most important
      sources of tremor. Characteristic of fatigue induced hand tremor and its dominant
      directional properties are reported in this work. For a fixed laparoscopic tool
      grip with temporally synchronized predefined task protocols, characteristics of
      fatigue induced tremors have been studied. Dominant component of tremor was found
      to be in the sagittal plane in case of both static and dynamic tasks. In order to
      relate it with the muscle fatigue level, spectral properties of surface
      electromyography (SEMG) were also investigated simultaneously. A study of
      transient effect on tool positioning was also included, which conjointly
      advocates the other experimental results on fatigue induced hand tremor as well. 

PMID- 25571495
TI  - Implanted electrodes for multi-month EEG.
AB  - An implanted electroencephalogram (EEG) recorder would help diagnose infrequent
      seizure-like events. A proof-of-concept study quantified the electrical
      characteristics of the electrodes planned for the proposed recorder. The
      electrodes were implanted in an ovine model for eight weeks. Electrode impedance
      was less than 800 Ohms throughout the study. A frequency-domain determination of
      sedation performed similarly for surface versus implanted electrodes throughout
      the study. The time-domain correlation between an implanted electrode and a
      surface electrode was almost as high as between two surface electrodes (0.86
      versus 0.92). EEG-certified clinicians judged that the implanted electrode
      quality was adequate to excellent and that the implanted electrodes provided the
      same clinical information as surface electrodes except for a noticeable amplitude
      difference. No significant issues were found that would stop development of the
      EEG recorder. 

PMID- 25571496
TI  - Optimal position of the transmitter coil for wireless power transfer to the
      implantable device.
AB  - The maximum deliverable power through inductive link to the implantable device is
      limited by the tissue exposure to the electromagnetic field radiation. By moving
      away the transmitter coil from the body, the maximum deliverable power is
      increased as the magnitude of the electrical field at the interface with the body
      is kept constant. We demonstrate that the optimal distance between the
      transmitter coil and the body is on the order of 1 cm when the current of the
      transmitter coil is limited to 1 A. We also confirm that the conditions on the
      optimal frequency of the power transmission and the topology of the transmission
      coil remain the same as if the coil was directly adjacent to the body. 

PMID- 25571497
TI  - A closed-loop inductive power control system for an instrumented strain sensing
      tibial implant.
AB  - Inductively-powered implantable biomedical devices are widely used nowadays,
      however the power variations due to the coil misalignment can significantly
      affect the device performance. A closed-loop power control system is proposed in
      this paper, which is implemented in a Subject-Carried Implant Monitoring
      Inductive Telemetric Ambulatory Reader (SCIMITAR) for remote strain data
      acquisition from an instrumented ovine tibia implant. The output power of the
      energizer is adaptively adjusted via a feedback circuitry connected the
      demodulator with the power energizer. Lab results showed that feedback suppressed
      variations in induced power caused by coil misalignment and extended the
      functional range of the device in axial and planar directions. 

PMID- 25571498
TI  - A 700mV low power low noise implantable neural recording system design.
AB  - A low power, low noise implantable neural recording interface for use in a Radio
      Frequency Identification (RFID) is presented in this paper. A two stage neural
      amplifier and 8 bit Pipelined Analog to Digital Converter (ADC) are integrated in
      this system. The optimized number of amplifier stages demonstrates the minimum
      power and area consumption; The ADC utilizes a novel offset cancellation
      technique robust to device leakage to reduce the input offset voltage. The neural
      amplifier and ADC both utilize 700mV power supply. The midband gain of neural
      amplifier is 58.4dB with a 3dB bandwidth from 0.71 to 8.26 kHz. Measured input
      referred noise and total power consumption are 20.7MUVrms and 1.90 respectively.
      The ADC achieves 8 bit accuracy at 16Ksps with an input voltage of +/-400mV.
      Combined simulation and measurement results demonstrate the neural recording
      interface's suitability for in situ neutral activity recording. 

PMID- 25571499
TI  - Characterization of ionic permeability and water vapor transmission rate of
      polymers used for implantable electronics.
AB  - Biocompatible polymers used as encapsulation and packaging materials for
      implantable electronic devices have to comply with numerous requirements.
      Especially their barrier properties against water molecules and ions are of
      particular interest regarding the reliability of the encapsulation as well as
      functional integrity of the electronic components since water and ions on the
      circuit board may evoke corrosion, leakage current and finally the failure of the
      device. This paper describes a measurement setup to investigate the ionic
      permeability under in vitro conditions of polymeric membranes manufactured from
      various biocompatible polymers. Ionic permeability and water vapor transmission
      rate representing the barrier properties of these membranes were investigated.
      First results were obtained for polyimide, silicone, polyether ether ketone and
      polyamide, whereas polyimide evinced the best properties. 

PMID- 25571500
TI  - Method for estimation of structural composition of skin layers based on light
      propagation simulation for liposuction applications.
AB  - Skin surface irregularity is the most common side effect after liposuction. To
      reduce this, it is necessary to devise a systematic method to provide structural
      composition details of skin layers, such as fat thickness and fat boundary tilt
      angle, for the plastic surgeon. Several commercial portable devices are available
      to measure skin layer information, working on the principle of a near-infrared
      technique using the light penetration properties of tissue in optical windows.
      However, these can only measure general fat thickness and not the structural
      compositions of skin layers with irregularities. Therefore, our goal in this
      paper is to propose a method to estimate the structural compositions of skin
      layers by analyzing and validating the relationship between light distribution
      and structural composition from simulation data based on specific structural
      conditions. 

PMID- 25571501
TI  - Instability detector of a fragile neural network: application to seizure
      detection in epilepsy.
AB  - It has recently been proposed that the epileptic cortex is fragile in the sense
      that seizures manifest through small perturbations in the synaptic connections
      that render the entire cortical network unstable. Therefore, one method for
      detecting seizures is to detect when the neuronal network has gone unstable. This
      is important for implementing a closed-loop therapy to suppress seizures. In this
      paper, we consider a widely used nonlinear stochastic model of a neuronal
      network, and assume that spiking dynamics during non-seizure periods correspond
      to certain synaptic connections that render its fixed point stable. We then apply
      a minimum energy perturbation theory we recently developed for networks to
      determine the changes in the most fragile node's synaptic connections that make
      the same fixed point unstable (our model during seizure). Then a detector is
      designed as follows. First a 2-state HMM is constructed (stable=state 1 and
      unstable=state 2) with fixed state transition probabilities, where the output
      observation is the firing rate of the most fragile node in the network. The
      output density functions are assumed to be Gaussian with parameters computed
      using maximum likelihood estimation on data generated from the nonlinear network
      model in each state. Then, to detect a transition from stable to unstable,
      spiking activity is simulated in all nodes from the nonlinear model. The detector
      first measures the firing rate of the fragile node, and computes the derivative
      of the cumulative likelihood ratio of the observed firing rate from the HMM's
      output distributions. When the derivative exceeds a certain threshold, a
      transition to the unstable state is detected. Various thresholds were tested when
      firing rate was computed by averaging over a different number of windows of
      different lengths. High performance was achieved and a tradeoff was found between
      the accuracy of the detector and the detection delay. 

PMID- 25571502
TI  - Generalizing performance limitations of relay neurons: application to Parkinson's
      disease.
AB  - Relay cells are prevalent throughout sensory systems and receive two types of
      inputs: driving and modulating. The driving input contains receptive field
      properties that must be transmitted while the modulating input alters the
      specifics of transmission. Relay reliability of a relay cell is defined as the
      fraction of pulses in the driving input that generate action potentials at the
      neuron's output, and is in general a complicated function of the driving input,
      the modulating input and the cell's properties. In a recent study, we computed
      analytic bounds on the reliability of relay neurons for a class of Poisson
      driving inputs and sinusoidal modulating inputs. Here, we generalize our analysis
      and compute bounds on the relay reliability for any modulating input.
      Furthermore, we show that if the modulating input is generated by a colored
      Gaussian process, closed form expressions for bounds on relay reliability can be
      derived. We applied our analysis to investigate relay reliability of thalamic
      cells in health and in Parkinson's disease (PD). It is hypothesized that in
      health, neurons in the motor thalamus relay information only when needed and this
      capability is compromised in PD due to exaggerated beta-band oscillations in the
      modulating input from the basal ganglia (BG). To test this hypothesis, we used
      modulating and driving inputs simulated from a detailed computational model of
      the cortico-BG-thalamo-cortical motor loop and computed our theoretical bounds in
      both PD and healthy conditions. Our bounds match well with our empirically
      computed reliability and show that the relay reliability is larger in the healthy
      condition across the population of thalamic neurons. Furthermore, we show that
      the increase in power in the beta-band of the modulating input (output of BG) is
      causally related with the decrease in relay reliability in the PD condition. 

PMID- 25571503
TI  - Dynamic steering of in vitro cortical neurons using field stimulation.
AB  - Neurological disorders are often characterized by abnormal neuronal activity. In
      the case of epilepsy, this can manifest itself in the form of uncontrolled
      synchronous activity often in the form of bursting. Pattern steering is the
      ability to apply stimulation to a network that effectively changes its dynamical
      firing pattern. In an epileptic network, the stimulation would be used to move
      the seizing network from its abnormal state to a normal state. This idea is
      explored here in cultured networks of cortical neurons plated on microelectrode
      arrays. Stimulation was applied to the bath resulting in an electric field
      generated throughout the network. This field was verified as sub-threshold in
      strength using a finite element model simulation. Stimulated networks showed a
      significant suppression in the number of bursts and increase in the interburst
      interval as compared to control networks. This observed burst suppression
      suggests that the sub-threshold stimulating field moved networks from a state of
      high frequency bursting to a state of low frequency bursting. 

PMID- 25571504
TI  - Implementation of the excitatory entorhinal-dentate-CA3 topography in a large
      scale computational model of the rat hippocampus.
AB  - The topography, or the anatomical connectivity, of the excitatory entorhinal
      dentate-CA3 circuit of the rat hippocampus has been implemented for a large
      scale, biologically realistic, computational model of the rat hippocampus. The
      implementation thus far covers only the excitatory synapses for the principal
      neurons in the hippocampal subregions. Starting from layer II of the entorhinal
      cortex, the projection of their perforant path axons has been mapped across the
      full extent of the dentate gyrus as well as to the CA3. The mossy fiber axon
      trajectories from the dentate granule cells to the CA3 pyramidal cells have been
      derived, incorporating the transverse route the fibers take through the CA3c and
      CA3b and the septo-temporal turn in the CA3a. The extensive arborization of the
      CA3 pyramidal axons have been modeled using 2-D, skewed Gaussian distributions
      which have been parametrized to exhibit the differences that exist among the
      CA3a, CA3b, and CA3c auto-associational projections. Using the limited samples
      available from the literature, key parameters for each projection have been
      interpolated as a function of transverse and/or septo-temporal position in order
      to create a more complete representation of the topography. 

PMID- 25571505
TI  - Generalized Volterra kernel model identification of spike-timing-dependent
      plasticity from simulated spiking activity.
AB  - This paper presents a methodology to estimate a learning rule that governs
      activity-dependent plasticity from behaviorally recorded spiking events. To
      demonstrate this framework, we simulate a probabilistic spiking neuron with spike
      timing-dependent plasticity (STDP) and estimate all model parameters from the
      simulated spiking data. In the neuron model, output spiking activity is generated
      by the combination of noise, feedback from the output, and an input-feedforward
      component whose magnitude is modulated by synaptic weight. The synaptic weight is
      calculated with STDP with the following features: (1) weight change based on the
      relative timing of input-output spike pairs, (2) prolonged plasticity induction,
      and (3) considerations for system stability. Estimation of all model parameters
      is achieved iteratively by formulating the model as a generalized linear model
      with Volterra kernels and basis function expansion. Successful estimation of all
      model parameters in this study demonstrates the feasibility of this approach for
      in-vivo experimental studies. Furthermore, the consideration of system stability
      and prolonged plasticity induction enhances the ability to capture how STDP
      affects a neural population's signal transformation properties over a realistic
      time course. Plasticity characterization with this estimation method could yield
      insights into functional implications of STDP and be incorporated into a cortical
      prosthesis. 

PMID- 25571506
TI  - Maximizing relaxation time in oscillator networks with implications for
      neurostimulation.
AB  - High frequency deep brain stimulation (HF-DBS) is a pervasive clinical
      neurostimulation paradigm in which rapid (> 100Hz) pulses of electrical current
      are invasively delivered to the brain. Here, we use dynamical systems analysis to
      provide hypotheses regarding the frequency-specificity of the therapeutic effects
      of HF-DBS. Using phase oscillator-based models, we study the relaxation time of a
      synchronized network following impulsive stimulation. In particular, by
      approximating a standard DBS pulse by a finite-energy (Dirac) delta function, we
      show the existence of a minimum bound on the frequency of stimulation necessary
      to keep the network in a desynchronized regime. If, as evidence suggests,
      pathological synchronization is central to the pathology in DBS-responsive
      disorders, then the analysis gives conceptual insight into why lower frequency
      and/or randomized stimulation therapy is less effective, and provides a way to
      study alternative design strategies. 

PMID- 25571507
TI  - Design, fabrication, and testing of a novel end-to-end vascular coupling system.
AB  - Microvascular anastomosis is common and necessary during reconstructive and free
      tissue transfer surgeries. Traditional hand suturing techniques are time
      consuming, subject to human error, and require complex instruments. Prior
      attempts including staples, ring-pin devices, cuffing devices, and clips were
      either more cumbersome, were unable to maintain a tight seal, or did not work for
      both arteries and veins. To provide a more efficient and reliable vessel
      anastomosis, a pin-free vascular coupling system that can be used for both
      arteries and veins was designed and manufactured. A set of corresponding
      instruments were developed to facilitate the anastomosis process. Both bench
      testing and ex vivo testing were performed to evaluate the operating abilities of
      the vascular coupling system. Preliminary studies were performed on cadaver pigs.

PMID- 25571508
TI  - Touchfree medical interfaces.
AB  - Real-time control of visual display systems via mid-air hand gestures offers many
      advantages over traditional interaction modalities. In medicine, for example, it
      allows a practitioner to adjust display values, e.g. contrast or zoom, on a
      medical visualization interface without the need to re-sterilize the interface.
      However, when users are holding a small tool (such as a pen, surgical needle, or
      computer stylus) the need to constantly put the tool down in order to make hand
      gesture interactions is not ideal. This work presents a novel interface that
      automatically adjusts for gesturing with hands and hand-held tools to precisely
      control medical displays. The novelty of our interface is that it uses a single
      set of gestures designed to be equally effective for fingers and hand-held tools
      without using markers. This type of interface was previously not feasible with
      low-resolution depth sensors such as Kinect, but is now achieved by using the
      recently released Leap Motion controller. Our interface is validated through a
      user study on a group of people given the task of adjusting parameters on a
      medical image. 

PMID- 25571509
TI  - Breast monitoring via time-domain microwave radar: early clinical trial study.
AB  - This work describes early results from our firststage clinical trial involving
      the monitoring of healthy volunteers with our time-domain microwave breast
      screening system. The system is composed of a 16-sensor multistatic array that
      records the electromagnetic energy scattered off of the breast tissue. All
      measurements are performed in the timedomain. We present here the system setup,
      patient-interface considerations, volunteer criteria and initial results from
      breast monitoring. 

PMID- 25571510
TI  - Monolithic superelastic rods with variable flexural stiffness for spinal fusion:
      simplified finite element analysis of an instrumented spine segment.
AB  - Rigid instrumentations have been widely used for spinal fusion but they come with
      complications, such as adjacent disc degeneration. Dynamic instrumentations have
      been tested but their efficiency (stabilization capability) and reliability
      (mechanical integrity of the implant) have yet to be proven. A monolithic Ti-Ni
      spinal rod with variable flexural stiffness is proposed to reduce the risks
      associated with spinal fusion while maintaining adequate stabilization. This
      publication presents a simplified numerical model capable of evaluating the
      eventual benefits of a Ti-Ni spinal rod with variable flexural stiffness.
      METHODS: A simplified instrumented spine segment model composed of six vertebrae
      and five discs has been developed. Two types of spinal rods were evaluated:
      Classic Ti instrumentation and Ti-Ni rods with variable stiffness. Both
      instrumentations were tested using two anchor configurations: pedicle screws only
      or a screws-cable combination. FINDINGS AND DISCUSSION: The all-screws
      configuration does not allow much motion with either classic Ti or variable Ti-Ni
      rods. The combination of a Ti rod with screws-cable anchoring allows more motion
      and, therefore, lower adjacent disk pressure, but puts extremely high stresses on
      the rod and anchors. The combination of the variable Ti-Ni rod and screws-cable
      anchoring leads to a significant decrease in adjacent disk pressure, without
      increasing stresses and pullout forces in the spinal instrumentation.

PMID- 25571511
TI  - Performance evaluation of low cost microfluidic chips made using a digital craft
      cutter for point of care applications in nucleic acid tests.
AB  - A point of care (POC) diagnostic system development for nucleic acid testing
      (NAT) for developing countries faces several challenges and barriers among which
      affordability is a very critical one [1,4]. Hence a study was made to evaluate
      the effectiveness of microfluidic chips made from a digital craft cutter to be
      used as a disposable cartridge. Low cost materials like double sided tapes,
      transparent sheets and connectors were used to realize the microfluidic chip [2].
      An in-house IVD sample preparation kit for nucleic acid extraction was used as a
      representative assay. Modifications were made to the assay workflow considering
      the feature sizes, design and volume of the microfluidic chip made from the paper
      cutter and other POC system requirements like turnaround time (TAT). The workflow
      was optimized by reducing overall TAT from 50min to 15min, sample volume from 150
      MUL to 12.5 MUL and reduced reagent volumes. The method was also optimized to
      work at an isothermal condition. The results showed good correlation and yield in
      terms of both quality and quantity when compared to results obtained from the
      established baseline protocol. Thus microfluidic chips made using a digital craft
      cutter can very well be a low cost alternative to manufacture disposable chips
      for POC applications in nucleic acid tests. 

PMID- 25571512
TI  - Grasp and force based taxonomy of split-hook prosthetic terminal devices.
AB  - In this paper, we analyze the use of the body-powered split-hook prosthetic
      terminal device, which is the most commonly used upper-limb prosthesis. We
      developed two taxonomies of split-hook use, one on grasp shape and one on force
      exertion, illustrating the functional capabilities and use cases of the device.
      Video captured from an amputee using a body-powered split-hook during a number of
      common activities was used to lend weight to the completeness of the
      classifications. These taxonomies serve to establish a common language and means
      of comparing the types of grasps achievable by simple terminal devices to those
      of advanced myoelectric terminal devices or even human hands. The first taxonomy
      categorizes the grasp type based on the contacts with the environment while the
      second is categorized by the method and limitation of force exertion. We discuss
      the difference between grasps capable of holding objects compared to those that
      are capable of acquiring objects and the importance of non-prehensile uses of the
      split-hook. The classification schemes lay the groundwork for further detailed
      study of split-hook use, and the discussion of the use cases described may help
      guide terminal device developers to create improved prostheses. 

PMID- 25571513
TI  - Distance bounded energy detecting ultra-wideband impulse radio secure protocol.
AB  - We present a demonstration of a novel protocol for secure transmissions on a
      Ultra-wideband impulse radio that includes distance bounding. Distance bounding
      requires radios to be within a certain radius to communicate. This new protocol
      can be used in body area networks for medical devices where security is
      imperative. Many current wireless medical devices were not designed with security
      as a priority including devices that can be life threatening if controlled by a
      hacker. This protocol provides multiple levels of security including encryption
      and a distance bounding test to prevent long distance attacks. 

PMID- 25571514
TI  - Development and usability of a personalized sensor-based system for pervasive
      healthcare.
AB  - Although a plethora of remote health monitoring systems have been proposed for
      chronic conditions, the challenge posed by the changing patient needs and the
      requirement for personalization in health monitoring to move beyond proprietary,
      difficult to extend, and unsustainable solutions still pertains. In this
      direction, we describe a mobile health system based on a smartphone,
      portable/wearable sensors for measuring the patient's physiological parameters,
      and back-end platforms for the health professionals to monitor the patient
      condition and configure monitoring plans in an individualized manner. A prototype
      system was developed based on a Service-oriented Architecture and integrating
      commercially available sensing devices. An experimental study has been conducted
      with 53 patients in order to investigate the usability of the proposed system.
      The patients were able to perform the majority of the target tasks successfully
      (Success Rate = 77%), while the perceived usability using the System Usability
      Scale (SUS) was found to be above average (SUS score = 73%), indicating that the
      patients overall perceived the system as both easy to use and useful. 

PMID- 25571515
TI  - Task independent identification of sensor location on upper limb from orientation
      data.
AB  - In this paper we describe a novel method for sensor placement identification, and
      demonstrate the effectiveness of this method on an upper limb neuroprothesis for
      tremor suppression under a variety of tasks. Our objective is to facilitate long
      term tremor monitoring; tremor is the most prevalent movement disorder. Two
      assumptions are made: 1) movement and tremor demonstrate an additive effect
      further down the kinematic chain; 2) most applications have chained or fixed
      sensor locations. These assumptions justify obtaining absolute location through
      identifying relative location and thus to allow us to simplify the classification
      algorithm. Seventeen tasks were performed by patients suffering from essential
      tremor or Parkinson's disease. Ten features were found that resulted in 98.30%
      average accuracy (min: 92.31%; max: 100%) for the best configuration,
      irrespective of the task being performed. The method presented here is an
      important step towards more user-friendly and context-aware neuroprostheses for
      tremor suppression and monitoring, and facilitates the use of wearable sensors by
      non-trained personnel. 

PMID- 25571516
TI  - Highly wearable galvanic skin response sensor using flexible and conductive
      polymer foam.
AB  - Owing to advancements in daily physiological monitoring technology, diverse
      healthcare applications have emerged recently. The monitoring of skin conductance
      responses has extensive feasibility to support healthcare applications such as
      detecting emotion changes. In this study, we proposed a highly wearable and
      reliable galvanic skin response (GSR) sensor that measures the signals from the
      back of the user. To enhance its wearability and usability, we employed flexible
      conductive foam as the sensing material and designed it to be easily attachable
      to (and detachable from) a wide variety of clothes. We evaluated the sensing
      reliability of the proposed sensor by comparing its signal with a reference GSR.
      The average correlation between the two signals was 0.768; this is sufficiently
      high to validate the feasibility of the proposed sensor for reliable GSR sensing
      on the back. 

PMID- 25571517
TI  - Co-variation of depressive mood and spontaneous physical activity evaluated by
      ecological momentary assessment in major depressive disorder.
AB  - The objective evaluation of depressive mood is thought to be useful for the
      diagnosis and treatment of depressive disorders. Thus, we investigated
      psychobehavioral correlates, particularly the statistical associations between
      momentary depressive mood and behavioral dynamics measured objectively, in
      patients with major depressive disorder (MDD). Patients with MDD (n = 14) wore a
      watch-type computer device and rated their momentary symptoms using ecological
      momentary assessment. Spontaneous physical activity in daily life, referred to as
      locomotor activity, was also continuously measured by an activity monitor built
      into the device. A multilevel modeling approach was used to model the
      associations between changes in depressive mood scores and the local statistics
      of locomotor activity simultaneously measured. The statistical model constructed
      indicated that worsening of depressive mood was associated with increased
      intermittency of locomotor activity, as characterized by a lower mean and higher
      skewness. Our findings suggest the presence of associations between momentary
      depressive mood and behavioral dynamics in patients with depression, which may
      lead to the continuous monitoring of the pathological states of MDD. 

PMID- 25571518
TI  - Basis selection for maximally independent EEG sources.
AB  - We suggest a solution to the following problem: "Given multichannel linear source
      mixture data Y, and an overcomplete dictionary, A, of source projections, ai, how
      can we construct a complete basis, A0, by selecting columns from A such that the
      sources X = A0(-1)Y are as statistically independent as possible from each
      other?". While conventional independent component analysis (ICA) methods learn
      the mixing matrix A0 from scratch given Y, we restrict ourselves to selecting
      basis vectors from a known overcomplete dictionary. We develop two methods based
      on modifications of the maximum likelihood equivalent of the Infomax approach and
      the reconstruction-ICA (RICA) algorithm. We show that on realistic synthetic
      electroencephalographic (EEG) data our algorithms can find the true sources in
      the case of a highly coherent dictionary while requiring relatively fewer data
      points compared to other algorithms. On real EEG data, our algorithms obtain
      higher mutual information reduction.

PMID- 25571519
TI  - Sparse Principal Component Analysis for the parsimonious description of glucose
      variability in diabetes.
AB  - Abnormal glucose variability (GV) is considered to be a risk factor for the
      development of diabetes complications. For its quantification from continuous
      glucose monitoring (CGM) data, tens of different indices have been proposed in
      the literature, but the information carried by them is highly redundant. In the
      present work, the Sparse Principal Component Analysis (SPCA) technique is used to
      select, from a wide pool of GV metrics, a smaller subset of indices that
      preserves the majority of the total original variance, providing a parsimonious
      but still comprehensive description of GV. In detail, SPCA is applied to a set of
      25 literature GV indices evaluated on CGM time-series collected in 17 type 1
      (T1D) and 13 type 2 (T2D) diabetic subjects. Results show that the 10 GV indices
      selected by SPCA preserve more than the 75% of the variance of the original set
      of 25 indices, both in T1D and T2D. Moreover, 6 indices of the parsimonious set
      are shared by T1D and T2D. 

PMID- 25571520
TI  - Modeling heart beat dynamics and fMRI signals during carotid stimulation by neck
      suction.
AB  - Central autonomic control on the cardiovascular system has been widely
      investigated in the last decades. More recently, with the advent of brain imaging
      techniques, considerable effort is being spent on defining the role of specific
      brain areas, and their dynamic network, acting on autonomic efferents. A way to
      assess autonomic modulation is offered by carotid stimulation. In this work, we
      propose a methodology to investigate autonomic control in carotid stimulation
      experiments using heartbeat series in combination with fMRI imaging. We modeled
      cardiovascular signals using the point process model, and processed fMRI data in
      order to estimate independent components of correlated information. Using cross
      correlation and surrogate analysis, we assessed the responsiveness of subjects to
      neck suction stimuli and identified stimulus-related fMRI independent components.

PMID- 25571521
TI  - Three-way parallel independent component analysis for imaging genetics using
      multi-objective optimization.
AB  - In the biomedical field, current technology allows for the collection of multiple
      data modalities from the same subject. In consequence, there is an increasing
      interest for methods to analyze multi-modal data sets. Methods based on
      independent component analysis have proven to be effective in jointly analyzing
      multiple modalities, including brain imaging and genetic data. This paper
      describes a new algorithm, three-way parallel independent component analysis
      (3pICA), for jointly identifying genomic loci associated with brain function and
      structure. The proposed algorithm relies on the use of multi-objective
      optimization methods to identify correlations among the modalities and maximally
      independent sources within modality. We test the robustness of the proposed
      approach by varying the effect size, cross-modality correlation, noise level, and
      dimensionality of the data. Simulation results suggest that 3p-ICA is robust to
      data with SNR levels from 0 to 10 dB and effect-sizes from 0 to 3, while
      presenting its best performance with high cross-modality correlations, and more
      than one subject per 1,000 variables. In an experimental study with 112 human
      subjects, the method identified links between a genetic component (pointing to
      brain function and mental disorder associated genes, including PPP3CC, KCNQ5, and
      CYP7B1), a functional component related to signal decreases in the default mode
      network during the task, and a brain structure component indicating increases of
      gray matter in brain regions of the default mode region. Although such findings
      need further replication, the simulation and in-vivo results validate the three
      way parallel ICA algorithm presented here as a useful tool in biomedical data
      decomposition applications. 

PMID- 25571522
TI  - Kmeans-ICA based automatic method for ocular artifacts removal in a motorimagery
      classification.
AB  - Electroencephalogram (EEG) recordings aroused as inputs of a motor imagery based
      BCI system. Eye blinks contaminate the spectral frequency of the EEG signals.
      Independent Component Analysis (ICA) has been already proved for removing these
      artifacts whose frequency band overlap with the EEG of interest. However, already
      ICA developed methods, use a reference lead such as the ElectroOculoGram (EOG) to
      identify the ocular artifact components. In this study, artifactual components
      were identified using an adaptive thresholding by means of Kmeans clustering. The
      denoised EEG signals have been fed into a feature extraction algorithm extracting
      the band power, the coherence and the phase locking value and inserted into a
      linear discriminant analysis classifier for a motor imagery classification. 

PMID- 25571523
TI  - Parallel ICA with multiple references: a semi-blind multivariate approach.
AB  - High data dimensionality poses a major challenge for imaging genomic studies. To
      address this issue, a semi-blind multivariate approach, parallel independent
      component analysis with multiple references (pICA-MR), is proposed. pICA-MR
      extracts imaging and genetic components in parallel and enhances inter-modality
      correlations. Prior knowledge is incorporated to emphasize genetic factors with
      specific attributes. Particularly, pICA-MR can investigate multiple genetic
      references to explore functional interactions among genes. Simulations
      demonstrate robust performances with Euclidean distance employed as a metric for
      reference similarity, where components pointed by the same references are
      reliably identified and the detection power is significantly improved compared to
      blind methods. 

PMID- 25571524
TI  - Maximal-radius multiscale entropy of cardiovascular variability: a promising
      biomarker of pathological mood states in bipolar disorders.
AB  - Complexity measures from Multiscale Entropy (MSE) analysis of cardiovascular
      variability may provide potential biomarkers of pathological mental states such
      as major depression. To this extent, in this study we investigate whether
      complexity of Heart Rate Variability (HRV) is also affected in mental disorders
      such as bipolar disorders (BD). As part of the European project PSYCHE, eight BD
      patients experiencing multiple pathological mood states among depression,
      hypomania, and euthymia (i.e., good affective balance) underwent long-term night
      recordings through a comfortable sensing t-shirt with integrated fabric
      electrodes and sensors. Standard radius, i.e., 20% of the HRV standard deviation,
      and a maximal-radius choice for the sample entropy estimation were compared along
      with a further multiscale Renyi Entropy analysis. We found that, despite the
      inter-subject variability, the maximal-radius MSE analysis is able to discern the
      considered pathological mental states of BD. As the current clinical practice in
      diagnosing BD is only based on verbal interviews and scores from specific
      questionnaires, these findings provide evidence on the possibility of using
      heartbeat complexity as the basis of novel clinical biomarkers of mental
      disorders. 

PMID- 25571525
TI  - Principal component analysis of heart rate variability data in assessing cardiac
      autonomic neuropathy.
AB  - Heart rate variability (HRV) is recognized to carry early diagnostic value
      regarding cardiac autonomic neuropathy (CAN). A number of different HRV analysis
      algorithms have been proposed for the assessment of CAN, each of them providing
      partly differing information about HRV time series. Instead of confining to a
      limited set of HRV features, a multi-dimensional approach incorporating a
      multitude of HRV parameters could be an optimal way of assessing the changes in
      HRV related to CAN. In this paper, principal component analysis (PCA) is used for
      analysing multi-dimensional HRV data of 11 patients with definite CAN and 71
      subjects without CAN. Using the two most significant principal components,
      patients with CAN were separated from subjects without CAN with 87% accuracy. 

PMID- 25571526
TI  - Filtering approach based on empirical mode decomposition improves the assessment
      of short scale complexity in long QT syndrome type 1 population.
AB  - This study assesses the complexity of heart period (HP) and QT variability series
      through sample entropy (SampEn) in long QT syndrome type 1 individuals. In order
      to improve signal-to-noise ratio SampEn was evaluated over the original series
      (SampEn0) and over the residual computed by subtracting the first oscillatory
      mode identified by empirical mode decomposition (SampEn(EMD1R)). HP and QT
      interval were continuously extracted during daytime (2:00-6:00 PM) from 24 hour
      Holter recordings in 14 non mutation carriers (NMCs) and 34 mutation carriers
      (MCs) subdivided in 11 asymptomatic (ASYMP) and 23 symptomatic (SYMP). Both NMCs
      and MCs belonged to the same family line. While SampEn0 did not show differences
      among the three groups, Samp(EnEMD1R) assessed over the QT series significantly
      decreased in ASYMP subjects. SampEn(EMD1R) identified a possible factor (i.e. the
      lower short scale QT complexity) that might contribute to the different risk
      profile of the ASYMP group.

PMID- 25571527
TI  - Visualization methods for assisting detection of cardiovascular neuropathy.
AB  - Visualization models can assist in understanding the complex pattern of disease,
      where the signs may be buried in complex data. In this work we propose a new
      method for visualization of data derived from Heart Rate Variability (HRV)
      analysis, to indicate whether a person has developed, or is developing, signs of
      definite Cardiac Autonomic Neuropathy (CAN). Here, the visualizations are
      compared with actual data recorded from people attending a diabetes clinic with
      and without definite CAN. Indications from the new visualization technique are
      compared to the results of established diagnostic measures using the Ewing
      battery of tests. We find the proposed method to offer useful insights into this
      disease, as rather than relying upon a binary yes/no decision, it offers a
      comprehensive picture of the complexity of this disease. 

PMID- 25571528
TI  - Effect of gender and diabetes on major depressive disorder using heart rate
      asymmetry.
AB  - In this study, we have investigated how heart rate asymmetry (HRA) changes in
      major depressive disorder (MDD) subjects with comorbid diabetes as well as in
      male and female. Depression score was determined based on PHQ-9 questionnaire and
      from 135 subjects 70 subjects were selected with 1000 or more RR intervals. Heart
      rate asymmetry is a Poincare plot based nonlinear technique to analyze the
      asymmetry using RR interval time-series signal. Three commonly used HRA indices
      Guzik's index (GI), Porta's index (PI) and Ehlers' index (EI) were used to
      understand the changes in HRA in MDD. Results indicate significantly (p<;0.05)
      different GI and EI values between 'Dep' and 'NonDep' subgroups in 'Combined'
      group. All three HRA indices are found significantly different in presence of
      depression in female subjects. These results provide better understanding about
      changes in HRA in MDD and HRA indices could be a plausible nonlinear HRV feature
      for differentiating Depression 'Dep' from NonDepression 'NonDep' group - i)
      without comorbid diabetes; ii) in Female subjects.

PMID- 25571529
TI  - Relationship between heart rate variability and angiotensinogen gene polymorphism
      in diabetic and control individuals.
AB  - Heart Rate Variability (HRV) is extensively used to investigate general Autonomic
      Nervous System (ANS) function and is affected by many factors including age,
      gender, pathology such as diabetes and genetic polymorphisms. One of these
      genetic polymorphisms is the Angiotensin Converting Enzyme (ACE) polymorphism
      corresponding to insertion (I) or deletion (D) of a 287-base pair sequence of DNA
      in intron 16 of the ACE gene (rs4340). Some studies have addressed the
      relationship between HRV and D/D, I/D and I/I ACE polymorphism while others
      combined I/D and I/I ACE groups. In this study HRV is determined for diabetic and
      control individuals with different ACE polymorphism considering either separate
      or combined I/D and I/I genotypes. Linear time domain parameters, entropy, low
      frequency and total power of HRV were found to be significantly different between
      diabetic and control individuals with combined I/I and I/D ACE polymorphism,
      while only entropy was different for diabetic and control subjects with D/D ACE
      genotype. Separate analysis of I/I and I/D genotypes was preferred for a thorough
      investigation of HRV and ACE polymorphism, as the combined analysis masked some
      differences in HRV parameters such as Poincare plot between ACE polymorphisms and
      diabetes status. Furthermore, a separate analysis demonstrated that most of the
      significant differences for HRV were between the diabetic group with I/I genotype
      and I/D and D/D groups. 

PMID- 25571530
TI  - Tissue specific arterial spin labeling fMRI: a superior method for imaging
      cerebral blood flow in aging and disease.
AB  - Cerebral blood flow (CBF) is a physiological correlate of brain function and
      metabolism and as such an essential parameter for investigating how aging and
      disease affect the brain. Arterial spin labeling (ASL) is an fMRI method that
      provides absolute measurement of CBF non-invasively and with higher spatial
      resolution than non-MRI methods. However, application of ASL in older populations
      is hampered by partial volume effects (PVE) and tissue dependent changes in CBF.
      We have developed a tissue-specific ASL method (ts-ASL) that provides 'flow
      density' measures by quantifying CBF for each tissue separately and independently
      of tissue content. Using simulated functional and structural images, we
      investigated the effects of brain atrophy and random noise on the SNR of GM CBF
      measured with conventional and ts-ASL. Results showed that: (1) For all noise
      levels, the SNR of ts-ASL was higher. For example, for a random Gaussian noise
      with standard deviation sigma = 4, the SNR of GM CBF obtained with ts-ASL was ~3
      times higher than the SNR of the conventional method. (2) In contrast to
      conventional ASL, which was substantially affected by brain atrophy, ts-ASL was
      virtually independent of it. (3) The sensitivity of ts-ASL for detecting focal
      changes in CBF (DeltaCBF) in the presence of atrophy and noise was also higher
      compared to the conventional method. In hippocampus, for 15% atrophy and Gaussian
      noise with sigma = 4, conventional and ts-ASL retrieved 73% and 90% of the
      modeled DeltaCBF, respectively. Taken together, these results indicate that ts
      ASL may be better suited for measuring CBF in the presence of atrophy and random
      noise, both of which are expected to increase with aging and disease. 

PMID- 25571531
TI  - Accurate classification of schizophrenia patients based on novel resting-state
      fMRI features.
AB  - There is a growing interest in automatic classification of mental disorders such
      as schizophrenia based on neuroimaging data. Most previous studies considered
      structural MRI, diffusion tensor imaging and task-based fMRI for this purpose.
      However, resting-state fMRI data has not been used much to evaluate
      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. In this study, we extract two types of
      features from resting-state fMRI data: functional network connectivity features
      that capture internetwork connectivity patterns and autoconnectivity features
      capturing temporal connectivity of each brain network. Autoconnectivity is a
      novel concept we have recently proposed. We used minimum redundancy maximum
      relevancy to select features. Classification results using support vector machine
      shows that combining these two types of features can improve the classification
      on a large resting fMRI dataset consisting of 195 patients with schizophrenia and
      175 healthy controls. We achieved the accuracy of 85% which is very promising. 

PMID- 25571532
TI  - Diffeomorphic registration with self-adaptive spatial regularization for the
      segmentation of non-human primate brains.
AB  - Cerebral aging has been linked to structural and functional changes in the brain
      throughout life. Here, we study the marmoset, a small non-human primate, in order
      to get insights into the mechanisms of brain aging in normal and pathological
      conditions. Imaging the brain of small animals with techniques such as MRI,
      quickly becomes a challenging task when compared with human brain imaging. Very
      often, a simple pre-processing step such as brain extraction cannot be achieved
      with classical tools. In this paper, we propose a diffeomorphic registration
      algorithm, which makes use of learned constraints to propagate the manual
      segmentation of a marmoset brain template to other MR images of marmoset brains.
      The main methological contribution of our paper is to explore a new strategy to
      automatically tune the spatial regularization of the deformations. Results show
      that we obtain a robust segmentation of the brain, even for images with a low
      contrast. 

PMID- 25571533
TI  - Validation of computational fluid dynamics methods with anatomically exact, 3D
      printed MRI phantoms and 4D pcMRI.
AB  - A new concept of rapid 3D prototyping was implemented using cost-effective 3D
      printing for creating anatomically correct replica of cerebral aneurysms. With a
      dedicated flow loop set-up in a full body human MRI scanner, flow measurements
      were performed using 4D phase contrast magnetic resonance imaging to visualize
      and quantify intra-aneurysmal flow patterns. Ultrashort TE sequences were
      employed to obtain high-resolution 3D image data to visualize the lumen inside
      the plastic replica. In-vitro results were compared with retrospectively obtained
      in-vivo data and results from computational fluid dynamics simulations (CFD).
      Rapid prototyping of anatomically realistic 3D models may have future impact in
      treatment planning, design of image acquisition methods for MRI and angiographic
      systems and for the design and testing of advanced image post-processing
      technologies. 

PMID- 25571534
TI  - An MRI-compatible, ultra-thin, flexible stimulator array for functional
      neuroimaging by direct stimulation of the rat brain.
AB  - We developed an MRI-compatible, ultra-thin, flexible stimulator array for the rat
      brain and performed functional MRI (fMRI) acquisition during direct electrical
      stimulation of the brain. This technique measured brain activity evoked by direct
      stimulation of the motor and the somatosensory cortex. In order to avoid MR
      signal loss due to interferences with the main static field and RF field in the
      MRI system, the stimulator array was made from a non-magnetic gold electrode of
      100-nm thickness on a 2-um-thick parylene substrate. By using this stimulator
      array, MR images without signal loss around conducting electrode pads were
      acquired, and fMRI acquisition during concurrent electrical stimulation of the
      cerebral cortex was achieved. Neuronal activity propagated to distant brain areas
      from the stimulated motor cortex. Positive blood oxygenation level dependent
      (BOLD) signals were observed with direct stimulation of the motor cortex, while
      negative BOLD signals were observed with direct stimulation of the somatosensory
      cortex. Interestingly, the pattern of brain activity evoked by direct stimulation
      of the somatosensory cortex was different from that evoked by electrical
      stimulation of the forepaw. 

PMID- 25571535
TI  - Amplitude of low frequency fluctuation in primary open angle glaucoma: a resting
      state fMRI study.
AB  - Primary open angle glaucoma (POAG) is a kind of progressive neuropathy with no
      clear cause. In the present fMRI study, a data-driven approach was employed to
      map the alteration of regional spontaneous activity in POAG patients by measuring
      the amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level
      dependent (BOLD) signal. Twenty one POAG patients and 22 age and gender matched
      healthy subjects participated in this study. We found that the abnormal ALFF
      values in the POAG patients compared with healthy controls were not only detected
      in the visual regions but also across the whole brain. We also found the
      correlations between ALFF values and the POAG stages for POAG patients. We
      concluded that the abnormality of spontaneous brain activity in patients with
      POAG existed in visual cortex as well as in distal brain regions associated with
      sensation, motion, emotion and psychology. And the abnormal spontaneous neural
      activity in different brain regions could be better detected by specific
      frequency bands. These findings might contribute to a better understanding of the
      pathophysiology of POAG. 

PMID- 25571536
TI  - Enhanced visualization of pulmonary perfusion in 4D dual energy CT images.
AB  - Pulmonary embolism (PE) affects up to 600,000 patients and contributes to at
      least 100,000 deaths every year in the United States alone. Diagnosis of PE can
      be difficult as most symptoms are unspecific. Computed Tomography (CT)
      angiography is the reference for diagnosing PE. CT angiography produces grayscale
      images with darker areas representing any mass filling defects, making the
      analysis of the images difficult. This article demonstrates a method using the
      combination of energy levels in Dual Energy CT images to highlight the presence
      of PE in the lung. The results show that pairing different energy levels from 40
      to 140 keV can increase the contrast between well perfused areas and
      underperfused areas of the lung. In addition, the visualization used in the
      current study complies with the window/level settings usually employed by
      radiologists. 

PMID- 25571537
TI  - Opacity-driven volume clipping for slice of interest (SOI) visualisation of multi
      modality PET-CT volumes.
AB  - Multi-modality positron emission tomography and computed tomography (PET-CT)
      imaging depicts biological and physiological functions (from PET) within a higher
      resolution anatomical reference frame (from CT). The need to efficiently
      assimilate the information from these co-aligned volumes simultaneously has
      resulted in 3D visualisation methods that depict e.g., slice of interest (SOI)
      from PET combined with direct volume rendering (DVR) of CT. However because DVR
      renders the whole volume, regions of interests (ROIs) such as tumours that are
      embedded within the volume may be occluded from view. Volume clipping is
      typically used to remove occluding structures by 'cutting away' parts of the
      volume; this involves tedious trail-and-error tweaking of the clipping attempts
      until a satisfied visualisation is made, thus restricting its application. Hence,
      we propose a new automated opacity-driven volume clipping method for PET-CT using
      DVR-SOI visualisation. Our method dynamically calculates the volume clipping
      depth by considering the opacity information of the CT voxels in front of the PET
      SOI, thereby ensuring that only the relevant anatomical information from the CT
      is visualised while not impairing the visibility of the PET SOI. We outline the
      improvements of our method when compared to conventional 2D and traditional DVR
      SOI visualisations. 

PMID- 25571538
TI  - Skeleton-based abdominal aorta registration technique.
AB  - Vascular diseases are the most challenging health problems in developed
      countries. The vascular segmentation as well as registration techniques are the
      topics of past and ongoing research activities. In this work we target an
      abdominal aorta registration technique. The developed methodology is useful in
      the assessment of abdominal aortic aneurysm treatment by visualizing the
      correspondence between pre- and postoperative Computed Tomography (CT) data. The
      presented approach makes it possible to match all voxels belonging to the aorta
      from different CT series. It is based on aorta lumen segmentation and graph
      matching method. To segment the lumen area a hybrid level-set active contour
      approach is used. The matching step is performed based on a path similarity
      skeleton graph matching procedure. The registration results have been tested on
      the database of 8 patients, for which two different contrast-enhanced CT series
      were acquired. All registration results achieved with our system and verified by
      an expert prove the efficiency of the approach and encourage to further develop
      this method. 

PMID- 25571539
TI  - Mesh optimization of vessel surface model for computer-aided simulation of
      percutaneous coronary intervention.
AB  - Percutaneous coronary intervention is the gold standard to coronary diseases in
      the past decades due to much less trauma and quick recovery. However, due to the
      traits of minimal invasiveness, clinicians have to defeat the difficulties in eye
      hand coordination during the procedure, which also makes it a non-trivial task in
      the catheterization lab. The computer-aided surgical simulation is designed to
      provide a reliable tool for the early stage of the training of the procedure. In
      this simulation system, the surface model of the vessels contribute the major
      part in the virtual anatomic environment. On the other hand, heavy interactions
      between the virtual surgical tools and the model surface occur during the
      training. In order to achieve acceptable performances, the patient-specific
      vessel surface model needs further process to adapt to this situation. We
      proposed in this paper an approach to optimize the meshes that consist the
      surface model with its application in consideration. The connectivity of the
      surface model is firstly checked. Next a smooth processing is applied without
      modifying the geometry of the largest-connected surface. Then the quantities of
      the polygons consisting the model surface are eliminated both dramatically and
      appropriately. The resultant surface model is applied in the validation test
      interacting with the virtual guidewire. 

PMID- 25571540
TI  - Accurate estimation of the myocardium global function from reduced magnetic
      resonance image acquisitions.
AB  - Evaluating the heart global function from magnetic resonance images is based on
      estimating a number of functional parameters such as the left ventricular (LV)
      volume, LV mass, ejection fraction, and stroke volume. Estimating these
      parameters requires accurate calculation of the volumes enclosed by the inner and
      outer surfaces of the LV chamber at the max contraction and relaxation states of
      the heart. Currently, this is achieved through acquisition and segmentation of a
      large number of short-axis (SAX) views of the LV, which is time-consuming and
      expensive. Reducing the number of acquisitions results in undersampling the LV
      surfaces and hence increases the calculation errors. In this work, we describe
      and evaluate a method for estimating the cardiac parameters from a small number
      of image acquisitions that includes one long-axis (LAX) view of the LV. In this
      method, the LAX contour is used to swipe the SAX contours to fill in the missed
      LV surface between the SAX slices. Results on 25 patients and CT phantoms shows
      that, given the same number of slices, the proposed method is superior to other
      methods. 

PMID- 25571541
TI  - 3D reconstruction of neurons in electron microscopy images.
AB  - With the prevalence of brain-related diseases like Alzheimer in an increasing
      ageing population, Connectomics, the study of connections between neurons of the
      human brain, has emerged as a novel and challenging research topic. Accurate and
      fully automatic algorithms are needed to deal with the increasing amount of data
      from the brain images. This paper presents an automatic 3D neuron reconstruction
      technique where neurons within each slice image are first segmented and then
      linked across multiple slices within the publicly available Electron Microscopy
      dataset (SNEMI3D). First, random Forest classifier is adapted on top of
      superpixels for the neuron segmentation within each slice image. The maximum
      overlap between two consecutive images is then calculated for neuron linking,
      where the adjacency matrix of two different labeling of the segments is used to
      distinguish neuron merging and splitting. Experiments over the SNEMI3D dataset
      show that the proposed technique is efficient and accurate. 

PMID- 25571542
TI  - Prediction of skin ages by means of multi-spectral light sources.
AB  - Assessment of skin aging is a complex biological process that depends on various
      internal and external factors but has become important due to personalized skin
      health and cosmetic treatments. Although there are a small number of attempts to
      assess the skin aging, they identify only one of the previously classified skin
      aging groups. The methods used to achieve it are also based generally on highly
      expensive measurement devices. This work therefore proposes novel low-cost skin
      aging assessment apparatus by using light back-scatter intensity level of Red,
      Blue, Green and Infrared bands. This is further enhanced by using a machine
      learning method to accurately predict actual skin age. The proposed method
      appears to be highly capable of capturing multi-layer cellular changes exhibited
      by the biological skin aging process and predicting skin ages with a root-mean
      square error of as low as 0.160 by using only four features based on the four
      multi-spectral light sources. This assessment kit seems to be the first of its
      kind, which is expected to bring great benefit to both personalized skin
      healthcare and cosmetic sectors. 

PMID- 25571543
TI  - Wavelet denoising and reconstruction of a microneedle embedded in human skin ex
      vivo using terahertz pulsed reflectance.
AB  - Biological tissue can show promising features in the terahertz region of the
      electro-magnetic spectrum but face the problem that the signal to noise ratio can
      be poor due to the low energy output from the measurement instrument coupled with
      the high absorbance of water in biological tissue. Wavelet denoising and
      reconstruction are known to be suitable digital signal processing filters for
      reflected terahertz energy when appropriate thresholds, scales and mother
      wavelets are chosen. In this article, we therefore describe a Wavelet transform
      based method for denoising reflections of THz energy from ex-vivo human skin with
      an embedded microneedle. The wavelet reconstruction was then successfully used to
      identify the microneedle from the reflected waveform. This technique is
      potentially useful to enhance in-depth analysis and visualisation of underlying
      skin layers, lesions and penetration depth for targeted drug delivery. 

PMID- 25571544
TI  - Total dermoscopy score calculation using quantitative measurements in digital
      dermoscopy.
AB  - The main contributions of this paper are an automated approach for applying the
      ABCDE rules in a digital dermoscopy platform with fixed settings and a new
      registration method specially designed for aligning and comparing follow-up
      digital dermoscopy images in order to evaluate the evolution over time parameter
      E. Experimental evaluations of the registration method are reported for image
      pairs acquired during follow-up examinations. 

PMID- 25571545
TI  - A cascade classifier for diagnosis of melanoma in clinical images.
AB  - Computer aided diagnosis of medical images can help physicians in better
      detecting and early diagnosis of many symptoms and therefore reducing the
      mortality rate. Realization of an efficient mobile device for semi-automatic
      diagnosis of melanoma would greatly enhance the applicability of medical image
      classification scheme and make it useful in clinical contexts. In this paper,
      interactive object recognition methodology is adopted for border segmentation of
      clinical skin lesion images. In addition, performance of five classifiers, KNN,
      Naive Bayes, multi-layer perceptron, random forest and SVM are compared based on
      color and texture features for discriminating melanoma from benign nevus. The
      results show that a sensitivity of 82.6% and specificity of 83% can be achieved
      using a single SVM classifier. However, a better classification performance was
      achieved using a proposed cascade classifier with the sensitivity of 83.06% and
      specificity of 90.05% when performing ten-fold cross validation. 

PMID- 25571546
TI  - Early melanoma diagnosis with mobile imaging.
AB  - We research a mobile imaging system for early diagnosis of melanoma. Different
      from previous work, we focus on smartphone-captured images, and propose a
      detection system that runs entirely on the smartphone. Smartphone-captured images
      taken under loosely-controlled conditions introduce new challenges for melanoma
      detection, while processing performed on the smartphone is subject to computation
      and memory constraints. To address these challenges, we propose to localize the
      skin lesion by combining fast skin detection and fusion of two fast segmentation
      results. We propose new features to capture color variation and border
      irregularity which are useful for smartphone-captured images. We also propose a
      new feature selection criterion to select a small set of good features used in
      the final lightweight system. Our evaluation confirms the effectiveness of
      proposed algorithms and features. In addition, we present our system prototype
      which computes selected visual features from a user-captured skin lesion image,
      and analyzes them to estimate the likelihood of malignance, all on an off-the
      shelf smartphone. 

PMID- 25571547
TI  - Detecting melanoma in dermoscopy images using scale adaptive local binary
      patterns.
AB  - Recent advances in the area of computer vision has led to the development of
      various assisted diagnostics systems for the detection of melanoma in the
      patients. Texture and color are considered as two fundamental visual
      characteristics which are vital for the detection of melanoma. This paper
      proposes the use of a combination of texture and color features for the
      classification of dermoscopy images. The texture features consist of a variation
      of local binary pattern (LBP) in which the strength of the LBPs is used to
      extract scale adaptive patterns at each pixel, followed by the construction of a
      histogram. For color feature extraction, we used standard HSV histograms. The
      extracted features are concatenated to form a feature vector for an image,
      followed by classification using support vector machines. Experiments show that
      the proposed feature set exhibits good classification performance comparing
      favorably to other state-of-the-art alternatives. 

PMID- 25571548
TI  - Emax monitoring by aortic pressure waveform analysis.
AB  - Emax- the maximal left ventricular elastance- is perhaps the best available
      scalar index of contractility. However, the conventional method for its
      measurement involves obtaining multiple ventricular pressure-volume loops at
      different loading conditions and is thus impractical. We previously proposed a
      more practical technique for tracking Emax from just a single beat of an aortic
      pressure waveform based on a lumped parameter model of the left ventricle and
      arteries. Here, we tested the technique against the conventional Emax measurement
      method in animals during inotropic interventions. Our results show that the
      estimated Emax changes corresponded fairly well to the reference changes, with a
      correlation coefficient of 0.793. With further development and testing, the
      technique could ultimately permit continuous and less invasive monitoring of
      Emax. 

PMID- 25571549
TI  - A framework for quantification of regional cardiac fibrosis from serial sections
      using 3D whole slide imaging.
AB  - Pathological cardiac fibrosis is important in predisposing the heart to
      arrhythmia and mechanical failure. The regional distribution of fibrosis is often
      described qualitatively and quantitatively in histological studies of animal
      hearts after staining collagen with specific colored stains. Currently this
      description is often piecemeal, as it lacks rigorous spatial registration,
      matching and methodological standardization between animals and between study
      groups. We propose a strategy for the quantification of regional fibrosis using
      the American Heart Association (AHA) cardiac segmentation model. We quantify
      fibrosis after whole heart 3D histological reconstruction in one normal rat heart
      and in one rat heart in right heart failure induced by monocrotaline. We then
      assess the minimum spaced histological sampling which allows for accurate
      assessment of regional fibrosis. We show that using every section of a set of 5
      MUm serial sections quantifies regional right ventricular fibrosis, with highly
      significant (p <; 0.001) differences between heart failure and control hearts. We
      show that the absolute error of collagen quantification is low when sections are
      taken spaced by up to 100 MUm (error 5.7+/-5.8%). Likewise, absolute error
      associated with sectioning starting position is low for sections spaced up to 100
      MUm (error 13.3+/-17.2%). Above 100 MUm section spacing quantification error is
      large (tending to 50%) and error associated with sectioning starting position is
      large (tending to 60%). 

PMID- 25571551
TI  - Model based non-invasive estimation of PV loop from echocardiography.
AB  - We introduce a model-based approach for the non-invasive estimation of patient
      specific, left ventricular PV loops. A lumped parameter circulation model is
      used, composed of the pulmonary venous circulation, left atrium, left ventricle
      and the systemic circulation. A fully automated parameter estimation framework is
      introduced for model personalization, composed of two sequential steps: first, a
      series of parameters are computed directly, and, next, a fully automatic
      optimization-based calibration method is employed to iteratively estimate the
      values of the remaining parameters. The proposed methodology is first evaluated
      for three healthy volunteers: a perfect agreement is obtained between the
      computed quantities and the clinical measurements. Additionally, for an initial
      validation of the methodology, we computed the PV loop for a patient with mild
      aortic valve regurgitation and compared the results against the invasively
      determined quantities: there is a close agreement between the time-varying LV and
      aortic pressures, time-varying LV volumes, and PV loops. 

PMID- 25571550
TI  - Graph-cuts based reconstructing patient specific right ventricle: first human
      study.
AB  - Right ventricular (RV) function is increasingly recognized to play an important
      role in the clinical status and long-term outcome in patients with congenital
      heart disease as well as ischemic cardiomyopathy with left ventricular
      dysfunction. However, quantification of RV characteristics and function are still
      challenging due to its complex morphology and its thin wall with coarse
      trabeculations. To assess RV functions quantitatively, establishing the patient
      specific model from medical images is a prerequisite task. This study aims to
      develop a novel method for RV model reconstruction. Magnetic resonance images
      were acquired and preprocessed. Contours of right ventricle, right atrium and
      pulmonary artery were manually delineated at all slices and all time frames. The
      contour coordinates as well as the medical image specifications such as image
      pixel resolution and slick thickness were exported. The contours were transformed
      to the correct positions. Reorientation and matching were executed in between
      neighboring contours; extrapolation and interpolation were conducted upon all
      contours. After preprocessing, the more dense point set was reconstructed through
      a variational tool. A Delaunay-based tetrahedral mesh was generated on the region
      of interest. The weighted minimal surface model was used to describe RV surface.
      The graphcuts technique, i.e., max-flow/min-cut algorithm, was applied to
      minimize the energy defined by the model. The reconstructed surface was extracted
      from the mesh according to the mincut. Smoothing and remeshing were performed.
      The CPU time to reconstruct the model for one frame was approximately 2 minutes.
      In 10 consecutive subjects referred for cardiac MRI (80% female), right
      ventricular volumes were measured using our method against the commercial
      available CMRtools package. The results demonstrated that there was a significant
      correlation in end-diastolic and end-systolic volumes between our method and
      commercial software (r= 0.89 for end-diastolic volume and r=0.79 for end-systolic
      volume, both P<;0.0001). The time to obtain right ventricular volumes was shorter
      using our method than commercial one. In conclusion, a new method for right
      ventricle reconstruction has been developed. We envisage that this automatic
      modeling tool could be used by radiographer and cardiologists to assess the RV
      function in diverse heart diseases. 

PMID- 25571552
TI  - Nonlinear multiscale circulation model reproducable linear end-systolic pressure
      volume relationship.
AB  - As a well-known property of the heart, many studies has reported that the left
      ventricular end-systolic pressure-volume relationship (ESPVR) is linear. However,
      the reason of the linearity is poorly understood. This article presents a
      multiscale circulation model to be a tool for theoretical analyses on the
      mechanism of the linearity of ESPVR. The model is composed of three sub-models; a
      detailed closed-loop lumped-parameter model for cardiovascular system, geometric
      left ventricle model, a comprehensive ventricular myocyte model. Although the
      present model integrates nonlinear sub-models, the model can successfully
      reproduce highly linear ESPVR without any arbitrary modifications. 

PMID- 25571553
TI  - Neural decoding of spoken vowels from human sensory-motor cortex with high
      density electrocorticography.
AB  - We present the first demonstration of single-trial neural decoding of vowel
      acoustic features during speech production with high performance. The ability to
      predict trial-by-trial fluctuations in speech production was facilitated by using
      high-density, large-area electrocorticography (ECoG) combined with an adaptive
      principal components regression. In experiments from two human neurosurgical
      patients with a high-density 256-channel ECoG grid implanted over speech
      cortices, we demonstrate that as much as 81% of the acoustic variability across
      vowels could be accurately predicted from the spatial patterns of neural activity
      during speech production. These results demonstrate continuous, single-trial
      decoding of vowel acoustics. 

PMID- 25571554
TI  - Time varying effective connectivity for describing brain network changes induced
      by a memory rehabilitation treatment.
AB  - In clinical practice, cognitive impairment is often observed after stroke. The
      efficacy of rehabilitative interventions is routinely assessed by means of a
      neuropsychological test battery. Nowadays, more evidences indicate that the
      neuroplasticity which occurs after stroke can be better understood by
      investigating changes in brain networks. In this study we applied advanced
      methodologies for effective connectivity estimation in combination with graph
      theory approach, to define EEG derived descriptors of brain networks underlying
      memory tasks. In particular, we proposed such descriptors to identify substrates
      of efficacy of a Brain-Computer Interface (BCI) controlled neurofeedback
      intervention to improve cognitive function after stroke. Electroencephalographic
      (EEG) data were collected from two stroke patients before and after a
      neurofeedback-based training for memory deficits. We show that the estimated
      brain connectivity indices were sensitive to different training intervention
      outcomes, thus suggesting an effective support to the neuropsychological
      assessment in the evaluation of the changes induced by the BCI-based cognitive
      rehabilitative intervention. 

PMID- 25571555
TI  - Cortical encoding of phonemic context during word production.
AB  - Brain-computer interfaces that directly decode speech could restore communication
      to locked-in individuals. However, decoding speech from brain signals still faces
      many challenges. We investigated decoding of phonemes - the smallest separable
      parts of speech - from ECoG signals during word production. We expanded on
      previous efforts to identify specific phoneme by identifying phonemes by where in
      the word they were formed. We evaluated how the context of phonemes in words
      affects classification results using linear discriminant analysis. The decoding
      accuracy of our linear classifier indicated the degree to which the context of a
      phoneme can be determined from the cortical signal significantly greater than
      chance. Further, we identified the spectrotemporal features that contributed most
      to successful decoding of phonemic classes. Finally, we discuss how this can
      augment speech decoding for neural interfaces. 

PMID- 25571556
TI  - Modeling vocalization with ECoG cortical activity recorded during vocal
      production in the macaque monkey.
AB  - Vocal production is an example of controlled motor behavior with high temporal
      precision. Previous studies have decoded auditory evoked cortical activity while
      monkeys listened to vocalization sounds. On the other hand, there have been few
      attempts at decoding motor cortical activity during vocal production. Here we
      recorded cortical activity during vocal production in the macaque with a
      chronically implanted electrocorticographic (ECoG) electrode array. The array
      detected robust activity in motor cortex during vocal production. We used a
      nonlinear dynamical model of the vocal organ to reduce the dimensionality of
      'Coo' calls produced by the monkey. We then used linear regression to evaluate
      the information in motor cortical activity for this reduced representation of
      calls. This simple linear model accounted for circa 65% of the variance in the
      reduced sound representations, supporting the feasibility of using the dynamical
      model of the vocal organ for decoding motor cortical activity during vocal
      production. 

PMID- 25571557
TI  - Using speech and electrocorticography to map human auditory cortex.
AB  - Much less is known about the organization of the human auditory cortex compared
      to non-human primate auditory cortices. In an effort to further investigate the
      response properties of human auditory cortex, we present preliminary findings
      from human subjects implanted with depth electrodes in Heschl's gyrus (HG) as
      part of their neurosurgical treatment of epilepsy. Each subject had
      electrocorticography (ECoG) responses taken from medial and lateral HG in
      response to both speech and non-speech stimuli, including during speech
      production. Responses were somewhat variable across subjects, but posteromedial
      HG demonstrated frequency following responses to the stimuli in all subjects to
      some degree. Results and implications are discussed. 

PMID- 25571558
TI  - Rapid and low-invasive functional brain mapping by realtime visualization of high
      gamma activity for awake craniotomy.
AB  - For neurosurgery with an awake craniotomy, the critical issue is to set aside
      enough time to identify eloquent cortices by electrocortical stimulation (ECS).
      High gamma activity (HGA) ranging between 80 and 120 Hz on electrocorticogram
      (ECoG) is assumed to reflect localized cortical processing. In this report, we
      used realtime HGA mapping and functional magnetic resonance imaging (fMRI) for
      rapid and reliable identification of motor and language functions. Three patients
      with intra-axial tumors in their dominant hemisphere underwent preoperative fMRI
      and lesion resection with an awake craniotomy. All patients showed significant
      fMRI activation evoked by motor and language tasks. After the craniotomy, we
      recorded ECoG activity by placing subdural grids directly on the exposed brain
      surface. Each patient performed motor and language tasks and demonstrated
      realtime HGA dynamics in hand motor areas and parts of the inferior frontal
      gyrus. Sensitivity and specificity of HGA mapping were 100% compared to ECS
      mapping in the frontal lobe, which suggested HGA mapping precisely indicated
      eloquent cortices. The investigation times of HGA mapping was significantly
      shorter than that of ECS mapping. Specificities of the motor and language-fMRI,
      however, did not reach 85%. The results of HGA mapping was mostly consistent with
      those of ECS mapping, although fMRI tended to overestimate functional areas. This
      novel technique enables rapid and accurate functional mapping. 

PMID- 25571559
TI  - Mechanical characterization of ART-treated Jurkat cells using optical tweezers.
AB  - Acute lymphoid leukemia is a common type of blood cancer and chemotherapy is the
      initial treatment of choice. Quantifying the effectiveness of a chemotherapeutic
      drug at the cellular level plays an important role in the process of the
      treatment. In this study, an optical tweezer was employed to characterize the
      mechanical properties of Jurkat cells exposed to artesunate (ART) as a
      chemotherapy. A mathematical model was developed to describe the mechanical
      characteristics of the cell membrane and its features. By comparing the modeling
      results against experimental results from the optical tweezer, the elastic
      modulus of the Jurkat cells before and after ART treatment was calculated. The
      results demonstrate an increase in the cell stiffness after treatment. Therefore,
      the elastic modulus of a cell membrane may be a useful biomarker to quantify the
      effectiveness of a chemotherapeutic agent. 

PMID- 25571560
TI  - A biological plausible Generalized Leaky Integrate-and-Fire neuron model.
AB  - This study introduces a new Generalized Leaky Integrate-and-Fire (GLIF) neuron
      model. Unlike Normal Leaky Integrate-and-Fire (NLIF) models, the leaking resistor
      in the GLIF model equation is assumed to be variable, and an additional term
      would have the bias current added to the model equation in order to improve the
      accuracy. Adjusting the parameters defined for the leaking resistor and bias
      current, a GLIF model could be accurately matched to any Hodgkin-Huxley (HH)
      model and be able to reproduce plausible biological neuron behaviors. 

PMID- 25571561
TI  - Discrete stochastic model for the generation of axonal trees.
AB  - In this work we propose a 2D discrete stochastic model for the simulation of
      axonal biogenesis. The model is defined by a third order Markov Chain. The model
      considers two main processes: the growth process that models the elongation and
      shape of the neurites and the bifurcation process that models the generation of
      branches. The growth process depends, among other variables, on the external
      attraction field generated by a chemoattractant molecule secreted by the target
      area. We propose an estimation scheme of the involved parameters from real
      fluorescent confocal microscopy images of single neurons within intact adult
      Drosophila fly brains. Both normal neurons and neurons in which certain genes
      were inactivated have been considered (two mutations). In total, 53 images (18
      normal, 21 type 1 mutant and 14 type 2 mutant) were used. The model parameters
      allow us to describe pathological characteristics of the mutated populations. 

PMID- 25571563
TI  - A bacterial spore model of pulsed electric fields on spore morphology change
      revealed by simulation and SEM.
AB  - A two-layered spore model was proposed to analyze morphological change of
      bacterial spores subjected under pulsed electric fields. The outer layer, i.e.
      spore coat, was defined by Mooney-Rivlin hyper-elastic material model. The inner
      layer, i.e. peptidoglycan and spore core, was modeled by applying additional
      adhesion forces. The effect of pulsed electric fields on surface displacement was
      simulated in COMSOL Multiphysics and verified by SEM. The electro-mechanical
      theory, considering spore coat as a capacitor, was used to explain concavity; and
      the thin viscoelastic film theory, considering membrane bilayer as fluctuating
      surfaces, was used to explain leakage forming. Mutual interaction of external
      electric fields, charged spores, adhesion forces and ions movement were all
      predicted to contribute to concavity and leakage. 

PMID- 25571562
TI  - Effects of mechanical properties on tumor invasion: insights from a cellular
      model.
AB  - Understanding the regulating mechanism of tumor invasion is of crucial importance
      for both fundamental cancer research and clinical applications. Previous in vivo
      experiments have shown that invasive cancer cells dissociate from the primary
      tumor and invade into the stroma, forming an irregular invasive morphology.
      Although cell movements involved in tumor invasion are ultimately driven by
      mechanical forces of cell-cell interactions and tumor-host interactions, how
      these mechanical properties affect tumor invasion is still poorly understood. In
      this study, we use a recently developed two-dimensional cellular model to study
      the effects of mechanical properties on tumor invasion. We study the effects of
      cell-cell adhesions as well as the degree of degradation and stiffness of
      extracellular matrix (ECM). Our simulation results show that cell-cell adhesion
      relationship must be satisfied for tumor invasion. Increased adhesion to ECM and
      decreased adhesion among tumor cells result in invasive tumor behaviors. When
      this invasive behavior occurs, ECM plays an important role for both tumor
      morphology and the shape of invasive cancer cells. Increased stiffness and
      stronger degree of degradation of ECM promote tumor invasion, generating more
      aggressive tumor invasive morphologies. It can also generate irregular shape of
      invasive cancer cells, protruding towards ECM. The capability of our model
      suggests it a useful tool to study tumor invasion and might be used to propose
      optimal treatment in clinical applications. 

PMID- 25571564
TI  - Entrainability of cell cycle oscillator models with exponential growth of cell
      mass.
AB  - Among various aspects of cell cycle, understanding synchronization mechanism of
      cell cycle is important because of the following reasons. (1)Cycles of cell
      assembly should synchronize to form an organ. (2) Synchronizing cell cycles are
      required to experimental analysis of regulatory mechanisms of cell cycles. (3)
      Cell cycle has a distinct phase relationship with the other biological rhythms
      such as circadian rhythm. However, forced as well as mutual entrainment
      mechanisms are not clearly known. In this study, we investigated entrainability
      of cell cycle models of yeast cell under the periodic forcing to both of the cell
      mass and molecular dynamics. Dynamics of models under study involve the cell mass
      growing exponentially. In our result, they are shown to allow only a limited
      frequency range for being entrained by the periodic forcing. In contrast, models
      with linear growth are shown to be entrained in a wider frequency range. It is
      concluded that if the cell mass is included in the cell cycle regulation, its
      entrainability is sensitive to a shape of growth curve assumed in the model. 

PMID- 25571565
TI  - Towards a large-scale recording system: demonstration of polymer-based
      penetrating array for chronic neural recording.
AB  - The brain is a massively interconnected network of specialized circuits. Even
      primary sensory areas, once thought to support relatively simple, feed-forward
      processing, are now known to be parts of complex feedback circuits. All brain
      functions depend on millisecond timescale interactions across these brain
      networks. Current approaches cannot measure or manipulate such large-scale
      interactions. Here we demonstrate that polymer-based, penetrating, micro
      electrode arrays can provide high quality neural recordings from awake, behaving
      animals over periods of months. Our results indicate that polymer electrodes are
      a viable substrate for the development of systems that can record from thousands
      of channels across months to years. This is our first step towards developing a
      1000+ electrode system capable of providing high-quality, long-term neural
      recordings. 

PMID- 25571566
TI  - Design and fabrication of a multi-electrode array for spinal cord epidural
      stimulation.
AB  - A detailed design, fabrication, characterization and test of a flexible multi
      site platinum/polyimide based electrode array for electrical epidural stimulation
      in spinal cord prosthesis is described in this paper. Carefully designed 8.4 MUm
      thick structure fabrication flow achieves an electrode surface modification with
      3.8 times enhanced effective surface area without extra process needed. Measured
      impedance and phase of two type of electrodes are 2.35+/-0.21 KOmega and 2.10+/
      0.11 KOmega, -34.25+/-8.07 degrees  and -27.71+/-8.27 degrees  at 1K Hz,
      respectively. The fabricated arrays were then in-vitro tested by a multichannel
      neural stimulation system in physiological saline to validate the capability for
      electrical stimulation. The measured channel isolation on adjacent electrode is
      about -34dB. Randles cell model was used to investigate the charging waveforms,
      the model parameters were then extracted by various methods. The measured charge
      transfer resistance, double layer capacitance, and solution resistance are 1.9
      KOmega, 220 nF and 15 KOmega, respectively. The results show that the fabricated
      array is applicable for electrical stimulation with well characterized
      parameters. Combined with a multichannel stimulator, this system provides a full
      solution for versatile neural stimulation applications. 

PMID- 25571567
TI  - High-density optrodes for multi-scale electrophysiology and optogenetic
      stimulation.
AB  - We demonstrate the design and implementation of hybrid optical-electrical probes
      ('optrodes') for high resolution electrophysiology and optogenetic stimulation of
      neurons in multiple brain areas. Our 64-channel implantable optrodes are
      minimally invasive (50 MUm * 20 MUm) and span 1~2 mm. To minimize tethering
      forces on the brain tissue a monolithic high-density flexible cable (6 MUm thin)
      connects the probe to a lightweight headstage (1.3 gr, 256 channel configuration)
      designed for awake, freely-behaving small animals. A polymer-based multi-channel
      photonic light delivery system is integrated on shank in a separate layer,
      providing local optogenetic stimulation of the neural population adjacent to the
      probe. The entire manufacturing process, including the nanofabrication of the
      optrodes, post-fabrication assembly, and surgical implantation procedures are
      designed to be scalable, high-yield, and high-throughput. 

PMID- 25571568
TI  - Web technology based microelectrode characterization instrument.
AB  - In order to track the on-going changes and ultimate reliability of neural
      recording and stimulation arrays, it is beneficial to regularly characterize
      electrode arrays within the use environment. Microelectrodes used for neural
      stimulation or recording research can have different behaviors in-vivo vs. in-
      vitro, and once implanted the success of the experiment often hinges upon knowing
      the stability, changes, or deterioration of the electrodes. This paper describes
      a new instrument that is capable of batch characterizing 16 electrodes using
      cyclic voltammetry, electrochemical impedance spectroscopy and charge injection
      measurements. The latest web based technology was applied to the software design,
      which greatly facilitates electrode data sharing among researchers. 

PMID- 25571569
TI  - Cuff electrodes for very small diameter nerves -- prototyping and first
      recordings in vivo.
AB  - A fabrication method for cuff electrodes to interface small nerves was developed.
      Medical grade silicone rubber conforms the body of the cuff and insulation of the
      wires, platinum was used as metal for the embedded wiring and contacts. Planar
      electrode arrays where fabricated using a picosecond laser and then positioned
      into a carrying tube to provide the third dimension with the desired inner
      diameter (O 0.3-0.5 mm). The post preparation of the cuffs after structuring
      allows the fabrication of a stable self-closing flap that insulates the opening
      slit of the cuff without the need of extra sutures. Basic for the success of the
      cuff is the laser-based local thinning of both the silicone rubber and the metal
      at defined sections. This is critical to permit the PDMS' body to dominate the
      mechanical properties. Finite element modeling was applied to optimize the
      displacement ability of the cuff, leading to design capable of withstanding
      multiple implantation procedures without wire damage. Furthermore, the contact's
      surface was roughened by laser patterning to increase the charge injection
      capacity of Pt to 285 MUC/cm(2) measured by voltage transient detection during
      pulse testing. The cuff electrodes were placed on a small sympathetic nerve of an
      adult female Sprague-Dawley rat for recording of spontaneous and evoked neural
      activity in vivo. 

PMID- 25571570
TI  - The effect of electrode geometry on electrochemical properties measured in
      saline.
AB  - The impedance, cyclic voltammetry, and charge-injection properties of
      rectangular, sputtered iridium oxide (SIROF) electrodes have been measured in
      buffered physiological saline over a range of geometric surface areas (GSA) and
      perimeter-to-area ratios (P/A). Electrodes with a higher P/A are expected to have
      a lower impedance and higher charge injection capacity (Q(inj)), and both these
      effects were evident for SIROF electrodes with a GSA in the range 0.0023-0.0031
      mm(2). However, the magnitude of the effect was modest. The increase in Q(inj)
      for rectangular electrodes with a P/A ranging from 94 to 255 mm(-1) was 21-26%
      depending on pulse width. There was a corresponding decrease in impedance (0.1 to
      10(5) Hz) with increasing P/A and an increase in the SIROF charge storage
      capacity calculated from cyclic voltammetry. To assess the full usefulness of
      high P/A electrodes for increasing the reversible Q(inj) of an electrode,
      measurements should now be extended to chronic in vivo preparations.

PMID- 25571571
TI  - Effects of tools inserted through snake-like surgical manipulators.
AB  - Snake-like manipulators with a large, open lumen can offer improved treatment
      alternatives for minimally-and less-invasive surgeries. In these procedures,
      surgeons use the manipulator to introduce and control flexible tools in the
      surgical environment. This paper describes a predictive algorithm for estimating
      manipulator configuration given tip position for nonconstant curvature, cable
      driven manipulators using energy minimization. During experimental bending of the
      manipulator with and without a tool inserted in its lumen, images were recorded
      from an overhead camera in conjunction with actuation cable tension and length.
      To investigate the accuracy, the estimated manipulator configuration from the
      model and the ground-truth configuration measured from the image were compared.
      Additional analysis focused on the response differences for the manipulator with
      and without a tool inserted through the lumen. Results indicate that the energy
      minimization model predicts manipulator configuration with an error of 0.24 +/-
      0.22mm without tools in the lumen and 0.24 +/- 0.19mm with tools in the lumen (no
      significant difference, p = 0.81). Moreover, tools did not introduce noticeable
      perturbations in the manipulator trajectory; however, there was an increase in
      requisite force required to reach a configuration. These results support the use
      of the proposed estimation method for calculating the shape of the manipulator
      with an tool inserted in its lumen when an accuracy range of at least 1mm is
      required. 

PMID- 25571572
TI  - Toward robotically assisted membrane peeling with 3-DOF distal force sensing in
      retinal microsurgery.
AB  - Retinal microsurgery requires steady and precise manipulation of delicate eye
      tissues in a very small space. Physiological hand tremor and lack of force
      sensing are among the main technical challenges, limiting surgical performance.
      We present a system that consists of the cooperatively controlled Steady-Hand Eye
      Robot and a miniaturized 3-DOF force sensing instrument to address these
      limitations. While the robot can effectively suppress hand tremor, enable steady
      and precise tissue manipulation, the force sensing instrument can provide three
      dimensional force measurements at the tool tip with submillinewton resolution.
      Auditory sensory substitution is used to give the user real time force
      information. Evaluation experiments are conducted using artificial and biological
      membrane peeling phantoms. Experimental results show that the robotic assistance
      and force-to-audio sensory substitution can effectively control the magnitude of
      the tool-to-tissue force. The direction profiles of the membrane peeling forces
      reflect the different delaminating strategies for different membrane phantoms. 

PMID- 25571574
TI  - Hand-held multi-DOF robotic forceps for neurosurgery designed for dexterous
      manipulation in deep and narrow space.
AB  - Neurosurgical procedures require precise and dexterous manipulation of a surgical
      suture in narrow and deep spaces in the brain. This is necessary for surgical
      tasks such as the anastomosis of microscopic blood vessels and dura mater
      suturing. A hand-held multi-degree of freedom (DOF) robotic forceps was developed
      to aid the performance of such difficult tasks. The diameter of the developed
      robotic forceps is 3.5 mm, and its tip has three DOFs, namely, bending, rotation,
      and grip. Experimental results showed that the robotic forceps had an average
      needle insertion force of 1.7 N. Therefore, an increase in the needle insertion
      force is necessary for practical application of the developed device. 

PMID- 25571573
TI  - Human eye phantom for developing computer and robot-assisted epiretinal membrane
      peeling.
AB  - A number of technologies are being developed to facilitate key intraoperative
      actions in vitreoretinal microsurgery. There is a need for cost-effective,
      reusable benchtop eye phantoms to enable frequent evaluation of these
      developments. In this study, we describe an artificial eye phantom for developing
      intraocular imaging and force-sensing tools. We test four candidate materials for
      simulating epiretinal membranes using a handheld tremor-canceling
      micromanipulator with force-sensing micro-forceps tip and demonstrate peeling
      forces comparable to those encountered in clinical practice. 

PMID- 25571575
TI  - Development of femoral bone fracture model simulating muscular contraction force
      by pneumatic rubber actuator.
AB  - In femoral fracture reduction, orthopedic surgeons must pull distal bone
      fragments with great traction force and return them to their correct positions,
      by referring to 2D-fluoroscopic images. Since this method is physically
      burdensome, the introduction of robotic assistance is desirable. While such
      robots have been developed, adequate control methods have not yet been
      established because of the lack of experimental data. It is difficult to obtain
      accurate data using cadavers or animals because they are different from the
      living human body's muscle characteristics and anatomy. Therefore, an
      experimental model for simulating human femoral characteristics is required. In
      this research, human muscles are reproduced using a McKibben-type pneumatic
      rubber actuator (artificial muscle) to develop a model that simulates typical
      femur muscles using artificial muscles. 

PMID- 25571576
TI  - Towards accurate robot-assisted neuroendoscopy using an ergonomic handling
      interface and a lightweight robot.
AB  - We considered a robot-assisted neuroendoscopy, and we developed a handling
      interface for linking a clinically-used endoscope to a lightweight robot (tool
      holder) with 7 DoFs. Such a robot holds potential for soft interaction with the
      surgeon, yet its intrinsic compliance must be suitably tamed not to lose tool
      targeting accuracy. Starting from practical specifications by neurosurgeons, we
      designed, fabricated and preliminarily assessed a compact and ergonomic handling
      interface. Such an interface permitted to easily insert/retract the tool (the
      measured force was 2 N), and to accurately hit a predefined target (the mean
      targeting error was below 0.5 mm, within the accuracy level of the optical
      tracker used for tool localization and pose). The feedback by neurosurgeons was
      very positive, thus encouraging further developments. 

PMID- 25571577
TI  - The importance of behavior theory in control system modeling of physical activity
      sensor data.
AB  - Among health behaviors, physical activity has the most extensive record of
      research using passive sensors. Control systems and other system dynamic
      approaches have long been considered applicable for understanding human behavior,
      but only recently has the technology provided the precise and intensive
      longitudinal data required for these analytic approaches. Although sensors
      provide intensive data on the patterns and variations of physical activity over
      time, the influences of these variations are often unmeasured. Health behavior
      theories provide an explanatory framework of the putative mediators of physical
      activity changes. Incorporating the intensive longitudinal measurement of these
      theoretical constructs is critical to improving the fit of control system model
      of physical activity and for advancing behavioral theory. Theory-based control
      models also provide guidance on the nature of the controllers which serve as the
      basis for just-in-time adaptive interventions based on these control system
      models. 

PMID- 25571578
TI  - The Kunming CalFit study: modeling dietary behavioral patterns using smartphone
      data.
AB  - Human behavioral interventions aimed at improving health can benefit from
      objective wearable sensor data and mathematical models. Smartphone-based sensing
      is particularly practical for monitoring behavioral patterns because smartphones
      are fairly common, are carried by individuals throughout their daily lives, offer
      a variety of sensing modalities, and can facilitate various forms of user
      feedback for intervention studies. We describe our findings from a smartphone
      based study, in which an Android-based application we developed called CalFit was
      used to collect information related to young adults' dietary behaviors. In
      addition to monitoring dietary patterns, we were interested in understanding
      contextual factors related to when and where an individual eats, as well as how
      their dietary intake relates to physical activity (which creates energy demand)
      and psychosocial stress. 12 participants were asked to use CalFit to record
      videos of their meals over two 1-week periods, which were translated into
      nutrient intake by trained dietitians. During this same period, triaxial
      accelerometry was used to assess each subject's energy expenditure, and GPS was
      used to record time-location patterns. Ecological momentary assessment was also
      used to prompt subjects to respond to questions on their phone about their
      psychological state. The GPS data were processed through a web service we
      developed called Foodscoremap that is based on the Google Places API to
      characterize food environments that subjects were exposed to, which may explain
      and influence dietary patterns. Furthermore, we describe a modeling framework
      that incorporates all of these information to dynamically infer behavioral
      patterns that may be used for future intervention studies. 

PMID- 25571579
TI  - Leveraging intensive longitudinal data to better understand health behaviors.
AB  - Behavioral scientists have historically relied on static modeling methodologies.
      The rise in mobile and wearable sensors has made intensive longitudinal data
      (ILD) -- behavioral data measured frequently over time -- increasingly available.
      Consequently, analytical frameworks are emerging that seek to reliably quantify
      dynamics reflected in these data. Employing an input-output perspective,
      dynamical systems models from engineering can characterize time-varying behaviors
      as processes of change. Specifically, ILD and parameter estimation routines from
      system identification can be leveraged together to offer parsimonious and
      quantitative descriptions of dynamic behavioral constructs. The utility of this
      approach for facilitating a better understanding of health behaviors is
      illustrated with two examples. In the first example, dynamical systems models are
      developed for Social Cognitive Theory (SCT), a prominent concept in behavioral
      science that considers interrelationships between personal factors, the
      environment, and behaviors. Estimated models are then obtained that explore the
      role of SCT in a physical activity intervention. The second example uses ILD to
      model day-to-day changes in smoking levels as a craving-mediated process of
      behavior change.

PMID- 25571580
TI  - Inertial measurements of free-living activities: assessing mobility to predict
      falls.
AB  - An exploratory analysis was conducted into how simple features, from acceleration
      at the lower back and ankle during simulated free-living walking, stair ascent
      and descent, correlate with age, the overall fall risk from a clinically
      validated Physiological Profile Assessment (PPA), and its sub-components.
      Inertial data were captured from 92 older adults aged 78-95 (42 female, mean age
      84.1, standard deviation 3.9 years). The dominant frequency, peak width from
      Welch's power spectral density estimate, and signal variance along each axis,
      from each sensor location and for each activity were calculated. Several
      correlations were found between these features and the physiological risk
      factors. The strongest correlations were from the dominant frequency at the ankle
      along the mediolateral direction during stair ascent (Spearman's correlation
      coefficient p = - 0.45) with anterioposterior sway, and signal variance of the
      anterioposterior acceleration at the lower back during stair descent (p = - 0.45)
      with age. These findings should aid future attempts to classify activities and
      predict falls in older adults, based on true free-living data from a range of
      activities. 

PMID- 25571581
TI  - A textile-based wearable system for the prolonged assessment of cardiac mechanics
      in daily life.
AB  - Seismocardiogram, SCG, can be detected over the 24 hours in ambulant subjects by
      a textile-based wearable system together with the electrocardiogram, ECG and
      respiration. In this pilot study we explored the possibility to derive 24 h
      profiles of cardiac time intervals, i.e. indexes of heart mechanical function,
      from the SCG recordings performed in daily life conditions by the above wearable
      system. Two healthy subjects were recruited for the study. They worn the system
      for 24 hours during a working day. From each recording, every 30 minutes the
      following parameters were derived from the ECG and SCG signals: RR interval, RRI,
      Pre-Ejection Period, PEP, Isovolumic Contraction Time, ICT, Left Ventricular
      Ejection Time, LVET, Isovolumic Relaxation Time, IRT. From the analysis it
      appears that 1) all parameters are characterized by a coefficient of variation in
      the same order of magnitude, and 2) 24 h LVET time profiles mirrors the long term
      RRI behavior. Common trends in PEP and ICT profiles were observed in one subject.
      This study indicates that indexes of cardiac mechanics can be derived from SCG
      recordings performed over the 24 hours. The obtained positive results encourage
      further studies to refine this methodology and confirm the present findings. 

PMID- 25571582
TI  - Understanding smoking behavior using wearable sensors: relative importance of
      various sensor modalities.
AB  - The Personal Automatic Cigarette Tracker (PACT) system, which consists of
      abdominal (AB) and thoracic (TC) breathing sensors, and a RF hand-to-mouth
      proximity sensor (PS), has proven to be useful in the detection and
      characterization of cigarette smoke inhalations. In this research, we further
      analyze the impact of subjects' anthropometric characteristics on the quality of
      sensor signals and evaluate the contribution of each sensor modality to the
      accuracy of the classifier for smoke inhalations detection. Results indicated
      that subjects with medium BMI, high BMI, and in a standing position were,
      respectively, 1.91, 4.74 and 4.32 times more likely to affect the quality of the
      breathing signal. Features extracted from TC+AB+PS, TC, AB, and PS sensors for
      individual detection models, resulted in F-scores of 94%, 85.39%, 88.54% and
      90.48% respectively. For group models, the F-scores were 67.12%, 41.46%, 46.56%
      and 59.14%. This indicates higher contribution of abdominal breathing and hand
      gestures to detection of smoke inhalations. 

PMID- 25571583
TI  - Task-relevance of grasping-related degrees of freedom in reach-to-grasp
      movements.
AB  - The kinematic redundancy of the human arm enables the rotation of the arm plane
      about the shoulder-wrist axis, represented by a swivel angle, which is affected
      by hand orientation when grasping. The coordination of grasping-related degrees
      of freedom (GR-DOFs), including swivel angle, forearm supination, wrist flexion
      and radial deviation, depends on their task-relevance, which can be quantified by
      the ratio of a joint's active motion range to its total motion range (R-AMR). The
      R-AMR values are computed across the target position and orientation to compare
      the task-relevance of the GR-DOFs. Statistical analysis of R-AMR values at the
      end of reach-to-grasp movements shows that among the GR-DOFs, radial deviation is
      most sensitive to changes in target position, while forearm supination is most
      sensitive to changes in target orientation. The forearm supination and swivel
      angle coordinate for energy-efficiency such that the swivel angle, which adjusts
      the posture of the whole arm, is largely unused until the forearm supination
      approaches its joint limit. The results further the understanding of the human
      motor control system in arm motion control and may benefit the design of the
      control algorithm for the upper limb exoskeleton. 

PMID- 25571584
TI  - Markerless motion capture using appearance and inertial data.
AB  - Current monitoring techniques for biomechanical analysis typically capture a
      snapshot of the state of the subject due to challenges associated with long-term
      monitoring. Continuous long-term capture of biomechanics can be used to assess
      performance in the workplace and rehabilitation at home. Noninvasive motion
      capture using small low-power wearable sensors and camera systems have been
      explored, however, drift and occlusions have limited their ability to reliably
      capture motion over long durations. In this paper, we propose to combine 3D pose
      estimation from inertial motion capture with 2D pose estimation from vision to
      obtain more robust posture tracking. To handle the changing appearance of the
      human body due to pose variations and illumination changes, our implementation is
      based upon Least Soft-Threshold Squares Tracking. Constraints on the variation of
      the appearance model and estimated pose from an inertial motion capture system
      are used to correct 2D and 3D estimates simultaneously. We evaluate the
      performance of our method with three state-of-the-art trackers, Incremental
      Visual Tracking, Multiple Instance Learning, and Least Soft-Threshold Squares
      Tracking. In our experiments, we track the movement of the upper limbs. While the
      results indicate an improvement in tracking accuracy at some joint locations,
      they also show that the result can be further improved. Conclusions and further
      work required to improve our results are discussed. 

PMID- 25571585
TI  - A study on estimation of planar gait kinematics using minimal inertial
      measurement units and inverse kinematics.
AB  - This paper describes a preliminary study of using four inertial measurement units
      (IMUs) attached to the heel and pelvis to estimate the joint angles of normal
      subjects during walking. The IMU, consisting of a 3-D accelerometer and
      gyroscope, is used to estimate the planar displacement of the heel and pelvis and
      the angular change of heel in one gait cycle. We then model the gait as a planar
      3R serial chain and solve its inverse kinematics by using such information. The
      results are validated by comparing the estimated joint angles of lower limbs
      (i.e. hip, knee and ankle angles) with an optical motion capture system. This
      study can benefit the future research on conducting complete lower limbs
      kinematics analysis with minimal and unobtrusive wearable sensors. 

PMID- 25571586
TI  - Kinematic characteristics of gait in middle-aged adults during level walking.
AB  - Middle-aged people have shown a high fall incidence and degeneration in gait
      stability, while few studies concern that. This study aimed to assess the
      kinematic characteristics of gait in middle-aged people compared with younger and
      older ones during level walking, and to find sensitive indicators to characterize
      degenerated gait stability in middle-aged people. 13 middle-aged (mean age=52.1
      years), with 13 older (mean age=74.8 years) and 13 young (mean age=23.3 years)
      healthy adults participated in this study. We assessed following gait parameters
      of the subjects during their level walking: 1) temporal-spatial gait parameters:
      normalized gait velocity, stride length, step length and their variability; 2)
      gait stability parameters: acceleration root mean square (RMS) of COM and its
      variability; and instantaneous COM-COP inclination angles. Compared with young
      and older subjects, middle-aged adults showed no significant difference in
      temporal-spatial gait parameters and their stride-to-stride variability
      (P>0.050); Compared with young subjects, middle-aged adults showed a significant
      higher value in medial-lateral (ML) direction of acceleration RMS of COM
      (P=0.038) and its stride-to-stride variability (P=0.030), as well as in COM-COP
      inclination angle (P=0.003). There was no significant difference in the above two
      parameters of gait stability between middle-aged and older subjects (P>0.050).
      Results illustrated that middle-aged subjects showed similar degenerated pattern
      in gait stability as the older ones in ML direction. Gait stability parameters,
      including ML acceleration of COM and its variability, as well as ML COM-COP
      inclination angle may help to characterize this degenerated gait stability. It's
      necessary for us to develop early interventions for middle-aged adults to prevent
      falls during walking. 

PMID- 25571587
TI  - A study of viscoelasticity index for evaluating muscle hypotonicity during static
      stretching.
AB  - Static stretching is widely used as a preventative treatment for musculoskeletal
      disabilities by providing muscle hypotonicity, which results from changes in
      muscle tissue structure. However, the quantitative evaluation of hypotonicity
      during stretching has had limited success owing to the confounding factor of
      mechanical stress relaxation. To resolve this problem, we propose a new
      evaluation method for hypotonicity based on a viscoelastic muscle model using
      fractional calculus, which is known to be effective for biomaterials. We made
      continuous measurements of rectus skin indentation during static stretching as an
      indicator of reaction force in the rectus femoris muscle. The viscoelastic ratio
      and modulus were computed from the indentation trace. Both viscoelastic
      parameters decreased significantly between the early and final phases of
      stretching. The results suggest that our method is useful for quantitative
      evaluation of muscle hypotonicity during stretching. 

PMID- 25571588
TI  - Simulation model of a lever-propelled wheelchair.
AB  - Wheelchair efficiency depends significantly on the individual adjustment of the
      wheelchair propulsion interface. Wheelchair prescription involves reconfiguring
      the wheelchair to optimize it for specific user characteristics. Wheelchair
      tuning procedure is a complicated task that is performed usually by experienced
      rehabilitation engineers. In this study, we report initial results from the
      development of a musculoskeletal model of the wheelchair lever propulsion. Such a
      model could be used for the development of new advanced wheelchair approaches
      that allow wheelchair designers and practitioners to explore virtually, on a
      computer, the effects of the intended settings of the lever-propulsion interface.
      To investigate the lever-propulsion process, we carried out wheelchair lever
      propulsion experiments where joint angle, lever angle and three-directional
      forces and moments applied to the lever were recorded during the execution of
      defined propulsion motions. Kinematic and dynamic features of lever propulsion
      motions were extracted from the recorded data to be used for the model
      development. Five healthy male adults took part in these initial experiments. The
      analysis of the collected kinematic and dynamic motion parameters showed that
      lever propulsion is realized by a cyclical three-dimensional motion of upper
      extremities and that joint torque for propulsion is maintained within a certain
      range. The synthesized propulsion model was verified by computer simulation where
      the measured lever-angles were compared with the angles generated by the
      developed model simulation. Joint torque amplitudes were used to impose the
      torque limitation to the model joints. The results evidenced that the developed
      model can simulate successfully basic lever propulsion tasks such as pushing and
      pulling the lever. 

PMID- 25571589
TI  - Multi-channel LED light source for fluorescent agent aided minimally invasive
      surgery.
AB  - Cancer is one of the most common and deadly diseases around the world. Amongst
      all the different treatments of cancer such as surgery, chemotherapy and
      radiation therapy, surgical resection is the most effective. Successful surgeries
      greatly rely on the detection of the accurate tumor size and location, which can
      be enhanced by contrast agents. Commercial endoscope light sources, however,
      offer only white light illumination. In this paper, we present the development of
      a LED endoscope light source that provides 2 light channels plus white light to
      help surgeons to detect a clear tumor margin during minimally invasive surgeries.
      By exciting indocyanine green (ICG) and 5-Aminolaevulinic acid (ALA)-induced
      protoporphyrin IX (PPIX), the light source is intended to give the user a visible
      image of the tumor margin. This light source is also portable, easy to use and
      costs less than $300 to build. 

PMID- 25571590
TI  - Estimating surgical needle deflection with printed strain gauges.
AB  - The ability to track surgical needle deflection during procedures such as
      therapeutic drug delivery, biopsies, and medical device implantation allows
      clinicians to minimize positioning errors and procedural complications due to
      instrument deviations. We describe the use of a novel strain gauge printing
      method to sensorize surgical needles for the purpose of sensing needle shape and
      deflection during surgical procedures. The additive vapor-deposition based sensor
      fabrication method used here is capable of applying strain gauges (and resistive
      circuit elements) with micron-scale features onto surgical instruments of varying
      curvature and material composition without the need for mechanical machining.
      This fabrication method is used to apply several strain gauges onto an 18 gauge
      core biopsy needle to sense deflections. Validation experiments demonstrate a
      gauge factor of 1.16 for the printed strain gauges and nominal needle deflection
      measurement resolution of 500 microns. 

PMID- 25571591
TI  - Wireless impedance measurements for monitoring peripheral vascular disease.
AB  - Wireless microdevices powered by ultrasound energy have been fabricated to
      measure and telemeter tissue impedance spectrums for applications in peripheral
      vascular disease monitoring. The system is characterized by simplicity of the
      implant consisting of only two electrical components. Ex vivo testing shows the
      potential for constructing tissue impedance spectrum plots over the range from 10
      Hz to 10 kHz by a device less than 1 mm in diameter and 1 cm long. The
      neurostimulator microdevice was powered by continuous waveform 650 kHz ultrasound
      with a swept-frequency amplitude modulation. The system was operated at safe
      ultrasound power levels on the order of 10-100 mW/cm(2). The device proved to be
      sensitive and able to measure tissue impedances over a broad range. Volume
      conducted signals carrying impedance information from the microdevice were
      remotely detected by surface biopotential electrodes. 

PMID- 25571592
TI  - Sleep monitoring using body sounds and motion tracking.
AB  - This paper presents a system for sleep monitoring that can continuously analyze
      snoring, breathing, sleep phases and the activity of the patient during the night
      and the beginning of the day. Early results show that the system can be used to
      detect the occurrence of obstructive sleep apnea syndrome (OSAS). OSAS is
      traditionally diagnosed using polysomnography, which requires a whole night stay
      at the sleep laboratory of a hospital, where the patient is attached to multiple
      electrodes and sensors. Our system detects heartbeats, breathing, snoring,
      sleeping positions and movements using a special electret microphone and an
      inertial measurement unit (IMU). The system first analyses the sleep using the
      acoustic information provided by the electret microphone. From the acoustic
      information breathing events and heartbeats are identified. The system also
      analyses the patient's activity and positions from data delivered by the IMU. The
      information from both sensors is fused to detect sleep events. First experiments
      show that the system is capable of detecting and interpreting relevant data to
      improve sleep monitoring. 

PMID- 25571593
TI  - Development of new muscle contraction sensor to replace sEMG for using in muscles
      analysis fields.
AB  - Nowadays, the technologies for detecting, processing and interpreting
      bioelectrical signals have improved tremendously. In particular, surface
      electromyography (sEMG) has gained momentum in a wide range of applications in
      various fields. However, sEMG sensing has several shortcomings, the most
      important being: measurements are heavily sensible to individual differences,
      sensors are difficult to position and very expensive. In this paper, the authors
      will present an innovative muscle contraction sensing device (MC sensor), aiming
      to replace sEMG sensing in the field of muscle movement analysis. Compared with
      sEMG, this sensor is easier to position, setup and use, less dependent from
      individual differences, and less expensive. Preliminary experiments, described in
      this paper, confirm that MC sensing is suitable for muscle contraction analysis,
      and compare the results of sEMG and MC sensor for the measurement of forearm
      muscle contraction. 

PMID- 25571594
TI  - Flexible intramuscular micro tube electrode combining electrical and chemical
      interface.
AB  - With the rapidly developed micromachining technology, various kinds of
      sophisticated microelectrodes integrated with micro fluidic channels are design
      and fabricated for not only electrophysiological recording and stimulation, but
      also chemical drug delivery. As many efforts have been devoted to develop rigid
      microprobes for neural research of brain, few researchers concentrate on
      fabrication of flexible microelectrodes for intramuscular electrophysiology and
      chemical interfacing. Since crude wire electrodes still prevail in functional
      electrical stimulation (FES) and electromyography (EMG) recording of muscle, here
      we introduce a flexible micro tube electrode combining electrical and chemical
      pathway. The proposed micro tube electrode is manufactured based on polymer
      capillary, which provide circumferential electrode site contacting with electro
      active tissue and is easy to manufactured with low cost. 

PMID- 25571595
TI  - Distributions in the error space: goal-directed movements described in time and
      state-space representations.
AB  - Manipulation of error feedback has been of great interest to recent studies in
      motor control and rehabilitation. Typically, motor adaptation is shown as a
      change in performance with a single scalar metric for each trial, yet such an
      approach might overlook details about how error evolves through the movement. We
      believe that statistical distributions of movement error through the extent of
      the trajectory can reveal unique patterns of adaption and possibly reveal clues
      to how the motor system processes information about error. This paper describes
      different possible ordinate domains, focusing on representations in time and
      state-space, used to quantify reaching errors. We hypothesized that the domain
      with the lowest amount of variability would lead to a predictive model of
      reaching error with the highest accuracy. Here we showed that errors represented
      in a time domain demonstrate the least variance and allow for the highest
      predictive model of reaching errors. These predictive models will give rise to
      more specialized methods of robotic feedback and improve previous techniques of
      error augmentation. 

PMID- 25571596
TI  - Choice stepping reaction time test using exergame technology for fall risk
      assessment in older people.
AB  - Accidental falls remain an important problem in older people. Stepping is a
      common task to avoid a fall and requires good interplay between sensory
      functions, central processing and motor execution. Increased choice stepping
      reaction time has been associated with recurrent falls in older people. The aim
      of this study was to examine if a sensor-based Exergame Choice Stepping Reaction
      Time test can successfully discriminate older fallers from non-fallers. The
      stepping test was conducted in a cohort of 104 community-dwelling older people
      (mean age: 80.7 +/- 7.0 years). Participants were asked to step laterally as
      quickly as possible after a light stimulus appeared on a TV screen. Spatial and
      temporal measurements of the lower and upper body were derived from a low-cost
      and portable 3D-depth sensor (i.e. Microsoft Kinect) and 3D-accelerometer.
      Fallers had a slower stepping reaction time (970 +/- 228 ms vs. 858 +/- 123 ms, P
      = 0.001) and a slower reaction of their upper body (719 +/- 289 ms vs. 631 +/-
      166 ms, P = 0.052) compared to non-fallers. It took fallers significantly longer
      than non-fallers to recover their balance after initiating the step (2147 +/- 800
      ms vs. 1841 +/- 591 ms, P = 0.029). This study demonstrated that a sensor-based,
      low-cost and easy to administer stepping test, with the potential to be used in
      clinical practice or regular unsupervised home assessments, was able to identify
      significant differences between performances by fallers and non-fallers. 

PMID- 25571597
TI  - Testing proprioception in intrinsic and extrinsic coordinate systems: is there a
      difference?
AB  - An intact position sense is considered important for neuromotor recovery, but the
      available methods and protocols for its assessment are still limited. In the
      clinical practice it is generally tested trough a bimanual position matching
      test, that consists of replicating with one arm the angular positions of the
      other arm in space (intrinsic coordinates matching). However, the same test could
      be carried out by matching the hand location in space (extrinsic coordinates
      matching). Is there any difference between the procedures that may be relevant to
      the evaluation of position sense deficits? In this study we compared the
      performance of eight right handed subjects and two stroke survivors with left
      hemiparesis performing the test in the two conditions. A robotic manipulandum
      passively moved the left arm of the participants in twenty-four positions in the
      workspace. Subjects had to match the left arm position with their right arm
      either in intrinsic or extrinsic coordinates. The results show that all the
      subjects (impaired and controls) performed better when using the extrinsic
      paradigm. 

PMID- 25571598
TI  - The great beauty: a neuroaesthetic study by neuroelectric imaging during the
      observation of the real Michelangelo's Moses sculpture.
AB  - Recent studies have been showed as the perception of real or displayed
      masterpieces by ancient or modern painters generate stable neuroelectrical
      correlates in humans. In this study, we collected the neuroelectrical brain
      activity correlated with the observation of the real sculpture of Michelangelo's
      Moses within the church where it is actually installed in a group of healthy
      subjects. In addition to the cerebral activity also the heart rate (HR) and the
      galvanic skin response (GSR) were collected simultaneously, to assess the
      emotional engage of the investigated population. The Moses sculpture was observed
      by the group from three different point of views, each one revealing different
      details of the sculpture. In addition, in each location the light conditions
      related to the specific observation of the sculpture were explicitly changed.
      Results showed that cerebral activity of the subjects varied significantly across
      the three different views and for light condition against no light condition
      (p<;0.04). Furthermore, the emotional engage estimated on the whole population is
      higher for a point of observation in which the Mose's face is directed toward the
      eyes of the observers (p<;0.02). Finally, the cerebral appreciation of the
      investigated group was found maximum from a perspective in which all the details
      of the sculpture could be easily grab by the eyes. Results suggested how the
      perception of the sculpture depends critically by the point of view of the
      observers and how such point of view can produce separate emotional and cerebral
      responses. 

PMID- 25571599
TI  - An electroencephalographic Peak Density Function to detect memorization during
      the observation of TV commercials.
AB  - Nowadays, there is a growing interest in measuring the impact of advertisements
      through the estimation of cerebral reactions. Several techniques and methods are
      used and discussed in the consumer neuroscience. In such a context, the present
      paper provides a novel method to estimate the level of memorization occurred in
      subjects during the observation of TV commercials. In particular, the present
      work introduce the Peak Density Function (PDF) as an electroencephalographic
      (EEG) time-varying variable which is correlated with the cerebral events of
      memorization of TV commercials. The analysis has been performed on the EEG
      activity recorded on twenty healthy subjects during the exposition to several
      advertisements. After the EEG recordings, an interview has been performed to
      obtain the information about the memorized scenes for all the video clips watched
      by the subjects. Such information has been put in correlation with the occurrence
      of transient peaks of EEG synchronization in the theta band, by computing the
      PDF. The present results show that the increase of PDF is positively correlated,
      scene by scene, (R=0.46, p<;0.01) with the spontaneous recall of subjects. This
      technology could be of help for marketers to overcome the drawbacks of the
      standard marketing tools (e.g., interviews, focus groups) when analyzing the
      impact of advertisements. 

PMID- 25571600
TI  - Assessment of gait nonlinear dynamics by inhomogeneous point-process models.
AB  - Point-process linear models of stride intervals have been recently proven to
      provide a unique characterization of human gait dynamics through instantaneous
      time domain features. In this study we propose novel instantaneous measures
      characterizing nonlinear gait dynamics using a quadratic autoregressive
      inhomogeneous point-process model recently devised for the instantaneous
      assessment of physiological, natural, and physical discrete dynamical systems.
      Our mathematical framework accounts for long-term information given by the past
      events of non-stationary non-Gaussian time series, expressed by a Laguerre
      expansion of the Wiener-Volterra terms. Here, we present a study of gait
      variability from data gathered from physionet.org, including 15 recordings from
      young and elderly healthy volunteers, and patients with Parkinson's disease.
      Results show that our instantaneous polyspectral characterization provides an
      informative tracking of the inherent nonlinear dynamics of human gait, which is
      significantly affected by aging and locomotor disabilities. 

PMID- 25571601
TI  - A UWB wireless capsule endoscopy device.
AB  - Wireless capsule endoscopy (WCE) presents many advantages over traditional wired
      endoscopic methods. The performance of WCE devices can be improved using high
      frequency communication systems such as Impulse Radio-Ultra-Wideband (IR-UWB) to
      enable a high data rate transmission with low-power consumption. This paper
      presents the hardware implementation and experimental evaluation of a WCE device
      that uses IR-UWB signals in the frequency range of 3.5 GHz to 4.5 GHz to transmit
      image data from inside the body to a receiver placed outside the body. Key
      components of the IR-UWB transmitter, such as the narrow pulse generator and up
      conversion based RF section are described in detail. This design employs a
      narrowband receiver in the WCE device to receive a control signal externally in
      order to control and improve the data transmission from the device in the body.
      The design and performance of a wideband implantable antenna that operates in the
      aforementioned frequency range is also described. The operation of the WCE device
      is demonstrated through a proof-of-concept experiment using meat. 

PMID- 25571602
TI  - Performance evaluation on FPGA-implemented UWB-IR receiver for in-body to out-of
      body communication systems.
AB  - In order to design an optimized transceiver structure of ultra wideband (UWB)
      transmission in in-body to out-of-body communications, it is necessary to make
      the transceiver structure be easily adjustable in order to realize a good
      communication performance in an experimental environment. For this purpose, we
      first implement our develop UWB-impulse radio (IR) receiver structure for the in
      body to out-of-body communication in a field programmable gate array (FPGA)
      board, and evaluate the fundamental communication performance of the FPGA
      implemented UWB-IR receiver by a biological-equivalent liquid phantom experiment.
      The FPGA configuration results indicate that our FPGA realization of the UWB-IR
      receiver has accomplished good communication performance with few FPGA slices.
      Moreover, the evaluation results in the liquid phantom experiment show that the
      FPGA-implemented UWB-IR receiver can achieve a bit error rate (BER) of 10(-3) up
      to a communication distance of 70 mm with ensuring a high data rate of 2 Mbps. 

PMID- 25571603
TI  - An ultra-wideband wire spiral antenna for in-body communications using different
      material matching layers.
AB  - In this work an ultra-wideband wire antenna was designed and fabricated for
      transmitting/receiving signals to/from inside the human body. The antenna
      provides high gain and thus high field intensity in its broadside direction;
      hence, a high energy density wireless can be established with the inner body. The
      proposed antenna operates in the frequency band of 3-10 GHz with an impedance of
      200 Ohms in free space. The antenna was embedded in different materials with
      permittivity values ranging from 12 to 74 in order to evaluate the matching layer
      effect on wave propagation from outside to inside the body. The antenna port
      impedance was adjusted by using matching circuits. The electric field intensity
      inside the human chest was calculated for different materials and depths. The
      best improvement in wave penetration was obtained for the frequency band of 750
      1000 MHz by embedding the antenna inside a material with permittivity equal to
      27. 

PMID- 25571604
TI  - Matching layer for path loss reduction in ultra wideband implant communications.
AB  - Real-time monitoring of various physiological signals is of utmost importance for
      the treatment of chronic conditions. Radio technology can enable real-time
      sensing and collection of physiological data to facilitate timely medication and
      early pre-hospital management of patients. This can be realized with the aid of
      implantable biomedical sensors with the capability to transmit wirelessly the
      collected information to an external unit for display and analysis. Currently,
      commercial wireless medical implantable sensors operate in frequencies below 1
      GHz with narrowband signals. Recently, it has been demonstrated that ultra
      wideband (UWB) signals could be also used for the radio interface of these
      devices. However, establishing an implant communication link in the allocated UWB
      spectrum of 3.1-10.6 GHz is challenging. The attenuation of UWB signals
      propagating through biological tissues at these frequencies is high. Part of
      these path losses are caused by the impedance mismatch between the two
      propagation environments (i.e., air and biological tissues) that constitute an
      implant communication link. This mismatch results in inefficient power
      transmission of the radio waves. In this paper we propose the use of a layer of
      dielectric material that can be applied on the patient's skin. The permittivity
      value of this matching layer has to be chosen such that wave coupling is
      maximized. Through numerical simulations we determined the appropriate
      permittivity value of a matching layer for UWB implant communication links in the
      human thorax for 1-6 GHz. Path loss reduction of up to 10 dB can be obtained in
      this frequency band. These results can help improve the use of UWB signals for
      other in-body biomedical devices like the wireless capsule endoscope (WCE). 

PMID- 25571605
TI  - Novel joint TOA/RSSI-based WCE location tracking method without prior knowledge
      of biological human body tissues.
AB  - This paper proposes a novel joint time of arrival (TOA)/received signal strength
      indicator (RSSI)-based wireless capsule endoscope (WCE) location tracking method
      without prior knowledge of biological human tissues. Generally, TOA-based
      localization can achieve much higher localization accuracy than other radio
      frequency-based localization techniques, whereas wireless signals transmitted
      from a WCE pass through various kinds of human body tissues, as a result, the
      propagation velocity inside a human body should be different from one in free
      space. Because the variation of propagation velocity is mainly affected by the
      relative permittivity of human body tissues, instead of pre-measurement for the
      relative permittivity in advance, we simultaneously estimate not only the WCE
      location but also the relative permittivity information. For this purpose, this
      paper first derives the relative permittivity estimation model with measured RSSI
      information. Then, we pay attention to a particle filter algorithm with the TOA
      based localization and the RSSI-based relative permittivity estimation. Our
      computer simulation results demonstrates that the proposed tracking methods with
      the particle filter can accomplish an excellent localization accuracy of around 2
      mm without prior information of the relative permittivity of the human body
      tissues. 

PMID- 25571606
TI  - Subject-friendly entire gastrointestinal screening with a single capsule
      endoscope by magnetic navigation and the Internet.
AB  - Ever since capsule endoscopy (CE) was introduced into clinical practice, we
      gastroenterologists have been dreaming of using this less invasive modality to
      explore the entire gastrointestinal (GI) tract. To realize this dream, we have
      developed a magnetic navigation system which includes real-time internet
      streaming of endoscopic video and some useful gadgets (position detection by
      means of magnetic impedance (MI) sensors and a modified capsule that is
      "weightless" in water). The design of the weightless capsule made it possible
      with 0.5T (Tesla) extracorporeal magnets to control the capsule beyond 20cm. A
      pair of MI sensors on the body surface could detect subtle magnetic flux
      generated by an intra-capsular magnet in the GI tract by utilizing the space
      diversity effect which eliminated the interference of terrestrial magnetism.
      Subjects underwent CE, during which they were free from confinement in the
      hospital, except for 1 hour when the capsule was manipulated in the stomach and
      colon. This study had a completion rate of 97.5%. The high completion rate
      indicates that our system (single capsule endoscopy-SCE) with further
      improvements could become a viable modality for screening of the entire GI tract.

PMID- 25571607
TI  - Technical feasibility of patient-friendly screening and treatment of digestive
      disease by remote control robotic capsule endoscopes via the internet.
AB  - A few types of steerable capsule endoscopes have been proposed but
      disappointingly their systems were not applicable to common endoscopic treatment
      or pathological diagnosis. This study validates the possibility of treatment and
      biopsy by using an internet-linked (wireless control via the internet) robotic
      capsule endoscope (iRoboCap). iRoboCap consisted of three parts: an imaging unit,
      a movement control unit and a therapeutic tool unit. Two types of iRoboCaps were
      designed, one was a submarine type (iRoboCap-S) and the other was an amphibious
      type (iRoboCap-A). They were remotely and wirelessly steered by a portable tablet
      device using Bluetooth and via the internet. The success rates of biopsy or
      clipping were evaluated in a phantom. Although the two prototypes have various
      problems that need improving, we hope that our robotic and wireless innovations
      have opened the door to new endoscopic procedures and will pioneer various new
      applications in medicine. 

PMID- 25571608
TI  - The mobile phone as a tool in the assessment of nonspecific abdominal pain.

PMID- 25571609
TI  - "Paediatric DNA coding: can't attend, won't attend".

PMID- 25571610
TI  - Gigantic left atrium - can surgery reverse the downward spiral of cardiac
      cachexia?

PMID- 25571611
TI  - Pleomorphic adenoma of the soft palate; an important benign disease in an unusual
      location.

PMID- 25571612
TI  - Mesenteric Castleman disease.

PMID- 25571613
TI  - Compliance with NICE head injury management guidelines in a busy district general
      hospital - is it asking too much?

PMID- 25571614
TI  - [Dr. Magda Neuwirth, the great representative of pediatric epileptology in
      Hungary, died on Mother's Day in 2014].

PMID- 25571615
TI  - Leadership in quality, safety and more.

PMID- 25571616
TI  - South Dakota health project news.

PMID- 25571617
TI  - Osteoporosis: don't forget men.

PMID- 25571618
TI  - A rare association of acute bacterial endocarditis with Henoch-Schonlein purpura
      (HSP) in an adult patient.
AB  - Henoch-Schonlein purpura (HSP) is a systemic, small vessel vasculitic disorder
      that mainly affects joint, skin, gastrointestinal tract and kidneys. It is
      primarily a disease of children that is typically self-limited, but 10 percent of
      cases occur in adults where features and outcomes may vary. The underlying
      pathogenesis of HSP remains unknown. We report a case of HSP that occurred with
      the onset of acute bacterial endocarditis (ABE) in an otherwise healthy 37-year
      old Native American male. The patient presented with fevers, fatigue, abdominal
      pain and renal failure and was found to have acute left-sided staphylococcal
      endocarditis. He subsequently developed small bowel perforation and purpuric
      rash. Initially he was treated with broad spectrum antibiotics and small bowel
      resection. However, resolution of HSP and the associated signs and symptoms was
      only achieved after treatment with oral steroids and plasmapheresis.

PMID- 25571619
TI  - High-grade pancreatic trauma in pediatric patients: two cases of successful non
      operative management.
AB  - INTRODUCTION: Pancreatic injury secondary to blunt abdominal trauma is a rare
      finding compared to other solid organ injuries. Diagnosis is difficult because of
      vague clinical presentation, quality of screening radiography and laboratory
      testing, and experience of practitioners. Furthermore, a lack of consensus on
      treatment modalities based on the organ injury scale (OIS) can further confuse
      management of pediatric patients. CASE REPORT: We report two cases of pediatric
      pancreatic trauma. Both involved ductal injury demonstrated on imaging. Both
      patients qualify as grade III injuries according to the OIS as developed by the
      American Association for the Surgery of Trauma. Both patients were managed non
      operatively using nasogastric suction, NPO, and total parenteral nutrition (TPN).
      Both patients had complete resolution of their pancreatic injury without
      pseudocyst formation or need for any operative intervention. CONCLUSION: The two
      cases presented illustrate severe pediatric pancreatic trauma resolving after a
      non-operative course. A lack of consensus exists on whether severe pancreatic
      trauma should be addressed operatively or non-operatively, owing to differences
      in hospital stay and cost to the patient, time to resolution, and need for TPN.
      The pediatric surgery community is equally divided between early operative
      intervention and non-operative management. Inexperience with pancreatic trauma
      diagnosis and work-up can lead to delayed treatment and poor clinical outcomes.
      These cases show successful early diagnosis with non-operative treatment and good
      long-term clinical results.

PMID- 25571621
TI  - Respiratory pathogen testing.
AB  - Respiratory tract infections (RTIs) are common in the pediatric population and
      contribute to a large portion of health care expenditure. A variety of modalities
      currently exist for testing for these pathogens in patients and as technology
      advances new, more efficient and specific tests are becoming available. This
      article reviews the most common causes of respiratory tract infections and the
      available testing modalities.

PMID- 25571620
TI  - Three new agents added to the arsenal to fight MRSA.

PMID- 25571622
TI  - Practice of medicine. Physician assistants.

PMID- 25571623
TI  - Quality focus: Nursing home collaborative.

PMID- 25571624
TI  - Industry in transition: what will 2015 bring?

PMID- 25571625
TI  - [Regulative effects of vessel active drugs on extremital skin temperature of
      experimental animals exposed to cold].
AB  - OBJECTIVE: Using an experimental model of animals exposed to cold to evaluate the
      regulative effects of prazosin hydrochloride (Pra) and racanisodamine (Ani) on
      extremital skin temperature of rats and mice. METHODS: Eighty animals were
      randomly divided into eight groups according to the drug dosage. After been
      administered with drugs by intragastric at room temperature for 60 min, the
      animals were moved into specified temperature (5 degrees C,18 degrees C)
      environment and the skin temperatures at the 1/3 site at the proximal end of tail
      were measured by infrared camera on 180 min and 300 min. Effects of drug were
      evaluated by changes in tail skin temperatures. RESULTS: Pra and Ani combination
      raised the extremital skin temperature of experimental animals significantly in a
      dose-dependent manner, while single use of Pra was not potent to rats and less
      potent to mice, and single use of Ani could not raise extremital skin temperature
      of both rats and mice. Change of rectal temperature in mice showed that Pra and
      Ani combination did not affect core temperature. CONCLUSION: Pra and Ani
      combination could significantly raise extremital skin temperature of rats and
      mice exposed to cold, and would not affect their core (rectal) temperature.

PMID- 25571626
TI  - [Roles of tyrosine hydroxylase expressed by CD4+ T cell subsets in collagen type
      II-induced arthritis].
AB  - OBJECTIVE: We used an animal model of collagen-induced arthritis (CIA) to study
      changes and roles of tyrosine hydroxylase (TH) expressed by CD4+ T cell subsets,
      and then explore the relationship between CD4+ T cell subset-derived
      catecholamines and inflammatory responses in CIA. METHODS: Thirty-six male DBA/1
      mice were randomly divided into control group, CIA model group (day 35) and CIA
      model group (day 55) (n = 12). CIA model was induced by type II collagen (CII) in
      DBA/1 mice. On the 35th and 55th day following primary immunization, the joints
      of the mice were observed for clinical score of swelling and the level of anti
      CII IgG antibody in serum was examined. Expression of specific transcription
      factors and cytokines of Th1, Th17, Th2 and Treg cells and TH in mesenteric lymph
      nodes was measured by means of Western blot. The changes of TH expressed by CD4+
      T cell subsets in mesenteric lymph nodes were determined by flow cytometry.
      RESULTS: Clinical score and anti-CII antibody level increased in CIA compared
      with that in intact mice. Specific transcription factors and cytokines expressed
      by Th1 and Th17 cells were upregulated and cytokines expressed by Th2 and Treg
      cells were downregulated in mesenteric lymph nodes in CIA mice. Expression of TH
      was upregulated and the increased expression of TH in CD4+ T cells was attributed
      to Th1 and Th17 cells in mesenteric lymph nodes of CIA. CONCLUSION: The increase
      in catecholamines from CD4+ T cell subsets in mesenteric lymph nodes of CIA may
      be related to inflammatory alleviation in CIA progression.

PMID- 25571627
TI  - [The effect of dezocine in prevention of adverse reaction of tracheal extubation
      in nasal endoscopic operation].

PMID- 25571628
TI  - [Effects of the rich selenium-banqiao-Codonopsis pilosula on the aged rats'
      immune functions and its underlying mechanism].
AB  - OBJECTIVE: To study the effects of the Rich Selenium-Banqiao-Codonopsis Pilosula
      (BCPA) injecta on the aged rats' immune functions and its underlying mechanism.
      METHODS: Totally 60 rats, composed of 2, 12 and 22 month age old (half male and
      half female), were served as a young group, middle-age group and aged group
      respectively. Each group rats were randomly divided into the control and the BCPA
      subgroup (n = 10). The BCPA group was injected with BCPA at 7.2 g/kg
      intraperitoneally every day and the control group was injected the same volume of
      normal saline. All rats were conventionally fed for 45 days. An immune injection
      was performed after 15 days of BCPA injection. On the 22nd day, late-onset immune
      response would be induced. The caudal vein blood was collected and the antigen
      specific IgG, IgG1 and IgG2a antibody was detected on the 15th, 30th and 45th
      day. On the 45th day, the major T cell subgroups of splenic cells were analyzed
      and splenic cells were proliferated. RESULTS: No significant difference in the
      delayed-type hypersensivity (DTH) reaction was found between the control and the
      BCPA subgroups in the young and middle-aged rats while the aged BCPA subgroup had
      a stronger DTH reaction. There was no significant difference in the blood content
      of specific IgG, IgG1 and IgG2a antibody between the young and middle-age BCPA
      group while the aged BCPA group rats had an obvious enhancing reaction to the
      three antibodies mentioned above (P < 0.05). There was no obvious difference in
      the number of the CD3+ lymphocytes and the CD4+ T helper lymphocytes between the
      control and the BCPA subgroup in the young aged rats while a significant increase
      was spotted between the middle-aged and the aged group (P < 0.05). The splenic
      cells from young BCPA group rats had a strong proliferation response (P < 0.05).
      CONCLUSION: BCPA can enhance DTH reaction, potentiate the production of specific
      IgG, IgG1 and IgG2a antibody to resist KLH, improve the reaction to antigen,
      increase the amount of CD4+ cell, promote the immune response and had an
      important role in anti-immunosenescence and antioxidant capacity improvement in
      the aged rats.

PMID- 25571629
TI  - [Effects of rutaecarpine on right ventriclar remodeling in rats with
      monocrotaline-induced pulmonary hypertension].
AB  - OBJECTIVE: To investigate the protective effects of rutaecarpine (Rut) on right
      ventricular remodeling in rats with monocrotaline-induced pulmonary hypertension
      (PH). METHOD: Forty-eight SD rats were fed adaptively for 1 week and then were
      randomly divided into the following 4 groups (n = 12): normal control group,
      monocrotaline (MCT) treatment group, MCT treatment with Rut (20 mg/kg)group and
      MCT treatment with Rut (40 mg/kg) group. PH rats were induced by a single
      injection of monocrotaline (60 mg/kg, sc) and were administered with Rut (20 or
      40 mg/kg/d) for 4 weeks. At the end of experiment, the right ventricular systolic
      pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored via the
      right jugular vein catheterization into the right ventricle. The ratio of right
      ventricle (RV) to left ventricle (LV) + septum (S) and the ratio of RV to tibial
      length were calculated. Right ventricular morphological changes were deserved by
      HE staining. Masson's trichrome staining was used to display collagen deposition.
      The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) levels in
      right ventricle were determined according to the manufacturer's instructions.
      mRNA and protein expression levels of NOX4, collagen I and collagen III were
      analyzed by immunohistochemisty, real-time PCR and Western blot. RESULTS: The
      results showed that Rut treatment for 4 weeks attenuated RVSP, mPAP and right
      ventricular remodeling index (RV/LV + S and RV/Tibial length) of PH rats induced
      by monocrotaline. Furthermore, the right ventricular collagen deposition and
      collagen I and collagen I expression induced by MCT were both significantly
      suppressed by Rut. The expression levels of NOX4 and MDA were obviously
      decreased, while the T-AOC was significantly increased in right ventricular from
      PH rats treated with Rut. CONCLUSION: These results suggested that Rut
      ameliorates the right ventricular remodeling in rats with PH induced by MCT
      through down-regulating of NOX4 expression and collagen accumulation.

PMID- 25571630
TI  - [The cloning of HIF-2alpha gene and hydroxylation assay of HIF-2alpha ODD domain
      in naked carp from Qinghai lake].

PMID- 25571631
TI  - [Purification of monoclonal antibody to clenbuterol and its biology identity].
AB  - OBJECTIVE: To identify the self-preparation monoclonal antibody which target to
      clenbuterol, and set up the standard curve to clenbuterol (CL) detection.
      METHODS: The affinity constants and activity of the monoclonal antibody which
      target to CL were determined by ELISA. ELISA was also used to confirm whether the
      monoclonal antibody had any across-reaction with BSA and CL analogues. The rat
      ascites which contains the monoclonal antibody target to CL was purified by
      (NH4)2SO4 salt-out method and further by affinity column. At last, the CL
      detection standard curve which based on indirect competition ELISA was
      established. RESULTS: The ELISA experiment showed that the antibody titer was
      10(6) and the monoclonal antibody affinity constants was 2.90 x 10(10) L/mol. The
      result of the indirect competition ELISA confirmed that the monoclonal antibody
      had no cross-reaction with BSA and a few kind of CL analogue. CL detection
      standard curve based on indirect competition ELISA was established, which R2 was
      0.9812, and the lowest detectable limit was 1.0 ng/ml. CONCLUSION: The standard
      curve based on indirectly competitioning ELISA was established. The self
      preparation monoclonal antibody which target to CL has high affinity and high
      specific to CL, which had established the foundation to the advanced development
      of the CL immune test paper and CL ELISA kit.

PMID- 25571632
TI  - [The effects of Kangai injection on enzyme activities of macrophages in rats].
AB  - OBJECTIVE: To study the effects of Kangai injection on the enzyme activities of
      macrophages and morphology of spleen and thymus from rats. METHODS: Twenty four
      male SD rats were randomly divided into two groups (n = 12), normal control group
      and experimental group. The rats in experimental group were injected with Kangai
      injection at the dosage of 5 ml/kg x d for 30 days peritoneally and those in
      control group were injected with nomal saline at the same volume. The content of
      supermicro protein was assayed by BCA method, the activities of lactate
      dehydrogenase (LDH), glutathione peroxidase(GSH-Px), and inducible nitric oxide
      synthase (iNOS) from alveolar macrophages(AM) and peritoneal macrophages (PM)
      were detected biochemically. The activities of acid phosphatase (ACP), superoxide
      dismutase(SOD) and succinate dehydrogenase (SDH) from AM and PM were detected by
      ELISA. The morphology of spleen and thymus were observed by light microscopy.
      RESULTS: The activities of LDH, GSH-Px and iNOS within AM and PM from
      experimental group were increased significantly compared with those of control
      group (P < 0.05). The activities of ACP, SOD and SDH in AM and PM from
      experimental group were also higher than those from control group (P < 0.05).
      Microscopically, there was thickening of peripheral arterial lymphatic sheath,
      enlargement of splenic lymphoid nodules with expended germinal center in the
      spleen of experimental group. There was no significant difference in the
      mophology of thymus between the two groups. CONCLUSION: Kangai injection may
      improve immune function by activating macrophages.

PMID- 25571635
TI  - [Yam polysaccharide on the prevention and cure of rats with diabetic
      nephropathy].

PMID- 25571633
TI  - [Long-term effects of heme oxygenase 1 overexpression on post-infarction heart
      function in diabetic rats].
AB  - OBJECTIVE: To clarify the impact of increased heme oxygenase-1 (HO-1) expression
      on cardiac function of diabetic rats with myocardial infarction and its
      mechanism. METHODS: Sixty adult male Wistar rats were randomly divided into five
      groups (n = 12): sham operation group (sham), diabetes + sham operation group (DM
      + sham), diabetes + MI group (DM + MI) , diabetes + myocardial infarction +
      cobalt original porphyrin (CoPP) group (DM + MI + CoPP), diabetes + myocardial
      infarction + CoPP+ tin porphyrin (SnMP) group (DM + MI + CoPP + SnMP). CoPP 4.5
      mg/kg or SnMP 15 mg/kg were administered at the day next to MI operation, for six
      weeks, once a week. At the 28th week post operation, the echocardiography, left
      heart via the carotid artery indoor intubation were used to observe the long-term
      influence of HO-1 inducer (cobalt protoporphyrin, CoPP) and activity of HO
      inhibitor (tin porphyrin, SnMP) on the indices of left ventricular remodeling and
      cardiac function after the intervention. Blood glucose (GLU), total cholesterol
      (TC), C-reactive protein (CRP), serum creatinine (Cr), aminotransferase (ALT) and
      other indicators were measured. ELISA was used to test interleukin-6 (IL-6),
      tumor necrosis factor (TNF), nitric oxide (NO), prostacyclin (PGI2), adiponectin,
      and ultra sensitive CRP (HsCRP) level. RESULTS: HO-1 inducer, CoPP, could
      ameliorate +/- dp/dtmax, left ventricular ejection fraction and left ventricular
      shortening fraction in diabetic myocardial infarction rats. It could also
      decrease left ventricular end-diastolic diameter. The serum bilirubin, NO and
      PGI2 levels, myocardial phosphorylated endothelial nitric oxide synthasee(peNOS),
      phosphorylated activated protein kinase (pAkt), phosphorylated adenosine
      monophosphate-activated protein kinase (pAMPK) expression were also significantly
      elevated, and the serum hs-CRP and TNF levels were significantly inhibited.
      Compared to inducer group, cardiac function were worse in the inhibitor group.
      CONCLUSION: Upregulated HO-1 level can improve the endothelial function, inhibite
      of the inflammatory response and enhance the antioxidant substances in serum
      bilirubin via peNOS-pAMPK pathway, which effectively inhibit ventricular
      remodeling and improve the long-term cardiac function after infarction in
      diabetic rats.

PMID- 25571634
TI  - [The cardioprotective effects of ischemic postconditioning on myocardial
      interstitium following ischemic/reperfusion in rats].
AB  - OBJECTIVE: To investigate the effects of ischemic postconditioning (IPTC) on the
      changes of matrix metalloproteinases-2 (MMP-2) and tissue inhibitor of
      metalloproteinase-2 (TIMP-2) protein and mRNA levels in rat heart subjected to
      ischemia/reperfusion, and explore the mechanism by which IPTC protects myocardial
      interstitium following ischemic/reperfusion (I/R). METHODS: Twenty four healthy
      male SD rats were randomly divided into 3 groups (n = 8): sham control (SC)
      group, I/R group and IPTC group. The parameters of left ventricular function
      including left ventricular systolic pressure (LVSP) and its derivate (+/-dp/dt)
      were measured; the amount of myocardial collagen contents was determined by
      hydroxyproline quantification; the plasma activity of creatine kinase (CK) and
      lactate dehydrogenase (LDH) was detected; the protien levels of MMP-2 and TIMP-2
      was measured by Western blot and the mRNA levels of MMP-2 and TIMP-2 was detected
      by real-time PCR. RESULTS: The myocardial collagen contents, left ventricular
      function and the protein and mRNA levels of TIMP-2 were significantly decreased
      in I/R group compared with those of SC group, wherease the activities of CK and
      LDH in the plasma and the protein and mRNA levels of MMP-2 were significantly
      enhanced in I/R group when compared to SC group. Compared with I/R group, the
      myocardial collagen contents, left ventricular function and the protein and mRNA
      levels of TIMP-2 were increased in IPTC group, the activities of CK and LDH in
      the plasma and the protein and mRNA level of MMP-2 were decreased in IPTC group.
      CONCLUSION: These findings indicate that IPTC has protective effects on
      myocardial interstitial after the myocardial ischemia/reperfusion injury, and
      IPTC may exert its cardioprotectve effect via inhibiting MMP-2 and enhancing TIMP
      2 expression in cardiac muscle.

PMID- 25571636
TI  - [Effects of citalopram on the expression of PCNA and C-fos and cell apoptosis in
      rat frontal cortical neurons after stress].
AB  - OBJECTIVE: To study the effects of citalopram on the expression of proliferating
      cell nuclear antigen (PCNA) and proto-oncogene protein (C-fos) and cell apoptosis
      in frontal cortical neurons of rat after stress. METHODS: Twenty four healthy
      male SD rats were randomly divided into three groups (n = 8): control group,
      stress group (treated with saline, ig) , experimental group (treated with
      Citalopram 4 mg/kg x d for 28 days, ig). Rats were forced to swim to establish
      chronic stress model. The protein expression levels of PCNA and C-fos were tested
      by immunohistochemistry assay. TUNEL assay was used to test cell apoptosis. Nikon
      image analysis software was used to determine the number of positive cells in
      each index. RESULTS: Compared with the control group, the stress group showed a
      smaller amount of PCNA-positive cells, a larger number of C-fos positive cells,
      and the volume of positive cells was significantly reduced. Compared with the
      stress group, the PCNA positive cells were increased significantly, the C-fos
      positive cells and TUNEL positive cells were decreased significantly, nuclear
      condensation phenomenon in frontal cortical neurons and the staining was
      significantly lighter in experimental group (P < 0.05). CONCLUSION: Citalopram
      significantly antagonize PCNA, C-fos protein expression and cell apoptosis of rat
      prefrontal cortical neurons caused by chronic stress, which might be the one of
      mechanisms of citalopram for prevention and treatment of psychosis caused by
      chronic stress.

PMID- 25571637
TI  - [Effects of the different living conditions on reproductive physiological
      functions of Chinese tree shrews].

PMID- 25571639
TI  - [Comparative study on purgative effect of three kinds of cultivated Rheum
      tanguticum].

PMID- 25571638
TI  - [Study on the protective effect of ursolic acid on alloxan-induced diabetic renal
      injury and its underlying mechanisms].
AB  - OBJECTIVE: To investigate the effect of ursolic acid (UA) on the alloxan-induced
      kidney injury in diabetic mice and explored its possible mechanisms. METHODS:
      Diabetes mellitus was induced in male Kunming mice by an injection of alloxan (70
      mg/kg, i.v.). After 72 hours, blood glucose levels were detected and mice with
      blood glucose levels over 13.9 mmol/L were considered as diabetic and selected
      for further experiment. Thirty mice were randomly divided into three groups:
      control, diabetic and diabetic + UA(35 mg/kg/d, i.g. continuously for 8 weeks).
      Blood glucose concentration, organ coefficient of kidney, blood urea nitrogen
      (BUN), creatinine (Cr) as well as renal tissue levels of superoxide dismutase
      (SOD), methane dicarboxylic aldehyde (MDA), tumor necrosis factor-alpha (TNF
      alpha) and interleukin-6 (IL-6) were determined. Pathology of the renal tissue
      was measured by hematoxylin-eosin staining. RESULTS: Compared to the control
      group, blood glucose, organ coefficient of kidney, BUN and Cr increased
      significantly. In addition, SOD activities was reduced markedly and levels of MDA
      and inflammatory factors (TNF-alpha, IL-6) increased significantly. Renal cells
      from model group rats showed atrophy and disordered after HE staining and
      infiltration of inflammatory cells also appeared in renal tissue of the model
      group. These changes were significantly attenuated in the diabetic group treated
      with UA. CONCLUSION: UA can significantly relieve renal damage in mice with
      diabetic nephropathy induced by alloxan, which might be related to decreased
      blood glucose level, antioxidation effect and inhibiting the production of
      inflammatory factors such as TNF-alpha and IL-6.

PMID- 25571640
TI  - [Study on the mechanism of how curcumin improves pulmonary vascular remodeling
      associated with chronic pulmonary arterial hypertension].
AB  - OBJECTIVE: To investigate the mechanism of how curcumin improves pulmonary
      vascular remodeling associated with chronic pulmonary arterial hypertension.
      METHODS: The model of chromic hypoxia hypercapniapulmoary remodeling was made.
      Twenty-four male rats were randomly divided into 4 groups (n = 6): group I
      (normoxia control group), group II (hypxia and hypercapnia model group), group II
      (disodium cromoglycate control group), group IV (curcumin treated group). The
      last 3 group rats were put in a hypoxia cabin where the concentrate of O2 was 8% 
      11% and the concentrate of CO2 was 3% - 5%, for 8 h a day and lasting 4 w in
      total. Group III rats were intraperitoneally injected with disodium cromoglycate
      (20 mg/kg) and group IV rats were administrated with curcumin by gavage (150
      mg/kg). The morphological changes of pulmonary vessel walls and the
      ultrastructure of mast cells were observed by the optics microscope and the
      transmission electron microscope. Mast cells and its degranulation state were
      measured by toluidine blue staining and immunohistochemistry. Data were expressed
      as means +/- SD (standard deviation) and analyzed with SPSS17.0 software.
      RESULTS: (1) By optics microscopy observation, the value of WA/TA was
      significantly higher in II group than other groups (P < 0.05). (2) Electron
      microscope showed that the endothelial cells of pulmonary arterioles in III and
      IV group were near to I group and the proliferation of pulmonary arterial media
      smooth cell layer and collagen fibers in adventitia was much lighter than those
      in II group. The membrane of mast cells was more intact in I, III, IV group than
      II group. (3) The number of mast cells, the degranulation rate of master cells
      and the number of positive tryptase stained cells in II group were significantly
      more than those in other groups. (P < 0.05). CONCLUSION: Curcumin may inhibit the
      remodeling of pulmonary vessel induced by chronic hypoxia hypercapnia by mast
      cell regulation.

PMID- 25571641
TI  - [Changs of EEG in the people of deacclimatization to high altitude].

PMID- 25571642
TI  - [Changs of Kappa opioid receptor expression in central amygdaloid nuclei during
      the process of chronic morphine-induced conditioned place aversion in rats].

PMID- 25571643
TI  - [Effects of 17beta-estradiol and estrogen receptor modulator on the expression of
      cadherin and catenin in the uterus of ovariectomized rats].

PMID- 25571644
TI  - [The potential effects of endoplasmic reticulum stress on the apoptosis of
      myocardial cells from mice with heart failure induced by acute viral myocarditis
      caused by B 3 Coxsackie virus].
AB  - OBJECTIVE: To explore the apoptotic pathway mediated by endoplasmic reticulum
      stress in the mouse myocardium with heart failure induced by acute viral
      myocarditis caused by B-3 Coxsackie virus. METHODS: Forty BALB/c male mice were
      randomly divided into 2 groups (n = 20): the control group and the virus
      infection group. The BALB/c mouse myocarditis was induced by B-3 Coxsackie virus
      and the mouse behavior was observed conventionally. All the mice were sacrificed
      on day 7 and the changes of left ventricular pressure (LVP) and the rate of
      change of left ventricular pressure (LV dp/dt) were measured. The cardiomyocytic
      apoptosis was analyzed by TUNEL method and the mRNA expression level of
      endoplasmic reticulum haperones glucose-regulated protein (GRP)78 and GRP94 was
      detected by RT-PCR. RESULTS: (1) Compared with those of control group, the
      parameters of cardiac hemodynamics in the virus infection group were
      significantly decreased (P < 0.01); (2) Compared with that of control group,
      myocardial apoptosis was significantly increased in the myocardial cells from
      mice with heart failure induced by acute viral myocarditis (P < 0.01); (3) The
      mRNA expression level of GRP78 and GRP94 were increased significantly in the
      virus infection group compared with the control group. CONCLUSION: These findings
      suggest the endoplasmic reticulum stress may mediate the apoptosis of myocardial
      cells in the mice myocardium of heart failure induced by acute viral myocarditis
      caused by B-3 Coxsackie virus.

PMID- 25571645
TI  - [Effect of Nrf2 and related factors on the progression of nonalcoholic
      steatohepatitis].
AB  - OBJECTIVE: To explore the role of NF-E2-related factor 2(Nrf2) and its related
      factors in the progression of nonalcoholi steatohepatitis (NASH) by investigating
      the alterations of lipid metabolism and liver histopathology as well as the
      changes of mRNA and protein expression levels of Nrf2 and its related factors in
      rats during NASH progression. METHODS: Male SD rats were randomly divided into
      normal group and model group, which were administrated with high fat diet to
      establish nonalcoholic steatohepatitis model. The rats from both groups were
      randomly killed at the end of 4, 12 weeks respectively. The levels of alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC),
      triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density
      lipoprotein cholesterol (LDL-C) were detected in the serum and liver tissue;
      Changes in fat deposition in liver tissue were determined by oil red O staining.
      HE staining were used to observe the pathological changes of liver tissue and to
      calculate nonalcoholic fatty liver disease (NAFLD) activity score (hepatic
      steatosis, inflammation and ballooning degeneration of liver cells). The
      expression of Nrf2 in liver was detected by immunohistochemical staining. The
      mRNA and protein levels of Nrf2 and related factors in liver were determined by
      Realtime PCR and Western blot, respectively. RESULTS: After 4 weeks of high fat
      diet, the levels of ALT, AST, TC in rat serum and TC, TG, LDL-C in liver were
      significantly increased compared with that of the normal group (P < 0.01, P <
      0.05). After 4 weeks of high fat diet, the levels of ALT, AST, TC, TG in serum
      and TC, TG, LDL- C in liver increased further (P < 0.01, P < 0.05). Until the
      12th week, the content of HDL-C in liver was significantly lower than that of the
      normal group (P < 0.05). At the end of the 4th or the 12th week, lipid droplets
      in the model rat liver cells were heavily dyed red and hepatic steatosis
      increased severely, with ballooning degeneration of liver cells. With the
      extension of high fat diet feeding time, fat deposition in the liver tissue,
      hepatic steatosis, NAFLD score, Nrl2 expression were significantly increased (P <
      0.01). Expression levels of mRNA and protein of Nrf2, heme oxyenase 1(HO1), NADPH
      quinone oxidoreductase 1(NQO1), gamma-glutamylcysteine synthethase (gamma-GCS),
      glutathione S-transferase (GST) in the model rats increased or decreased at the
      end of the 4th or the 12th week differentially, (P < 0.01, P < 0.05) with the
      more significant changes at the end of the 4th week than the 12th week.
      CONCLUSION: Nrf2 and its related factors may be involved in the occurrence and
      development of nonalcoholic fatty liver disease, which may play an important role
      in the process of NASH formation.

PMID- 25571646
TI  - [The protective effects of sacral nerve electrostimulation on intestinal mucosal
      mechanical barrier in rats with spinal cord injury].
AB  - OBJECTIVE: To study the protective effects of sacral nerve root
      electrostimulation on intestinal mechanical barrier in rats with spinal cord
      injury (SCI). METHODS: Fifty six Wistar rats were divided into normal group, SCI
      control group and SCI group with sacral nerve root electrostimulation (8 rats in
      each subgroup at 24, 48, 72 h after spinal cord injury). The following
      experiments were performed respectively in rats from the 3 groups: bacteria
      culture from intestinal mesentery lymph nodes, liver, spleen, intestinal
      morphology observation and detection the protein expression level of ZO-1.
      RESULTS: The intestinal mucosa appeared different degree of damage in SCI control
      group; cell-cell connections between intestinal epithelial cells were destroyed;
      Endotoxin levels in blood and the number of bacterial translocation increased
      obviously. Sacral nerve stimulation was found toimprove the intestinal mucosal,
      reduce the endotoxin content in the blood to normal level and the decrease the
      incidences of bacterial translocation of the gut origin. The expression of tight
      junction protein ZO-1 of rat intestinal tissue had no statistical differences
      among the 3 groups. On the other hand, the distribution of tight junction protein
      ZO-1 appeared different degrees of scattered and irregular in the control group
      while that in the experimental group appeared different degree of improvement as
      determined by the immunohistochemistry of rat intestinal tissue. CONCLUSION:
      sacral nerve root electrostimulation can rehabilitate the peristalsis of
      denervated colon, promote defeacation and decrease bacterial amount, protection
      of the intestinal mechanical barrier between intestinal epithelial cells and
      tight junction, reducing the endotoxin content in the blood and suppressing
      bacterial translocation from the gut.

PMID- 25571648
TI  - [Statistical analysis of papers in Chinese Journal of Applied Physiology from
      2009 to 2013].
AB  - OBJECTIVE: To analyze the status and papers information of Chinese Journal of
      Applied Physiology, and provide a guide for authors, readers and editing staffs.
      METHODS: We retrieved papers of Chinese Journal of Applied Physiology from 2009
      to 2013 from CNKI, and performed a statistical analysis of papers information
      contained in the text using bibliometrics method. Papers information such as
      document type, found support, author affiliation type, and discipline
      classification, etc. was analyzed. RESULTS: Seven hundred and forty two papers
      including 27 full English articles in total were published in Chinese Journal of
      Applied Physiology from 2009 to 2013. More papers were supported by national,
      provincial, and the other foundation, it was about 82.6% of all papers.
      CONCLUSION: Chinese Journal of Applied Physiology has stable manuscript
      resources, various discipline papers, and play an important role for development
      of applied physiology in China.

PMID- 25571647
TI  - [Effects of tank operation on renal function of crews].
AB  - OBJECTIVE: To explore the effects of harmful factors in tank cabins on renal
      function of tank crews. METHODS: One hundred and fifty two tank crews as the
      observation group and 37 soldiers without tank environment exposure as control
      group were selected in the study. alpha1-microglobulin(alpha1-MG), beta2
      microglobulin(beta2-MG), IgG, N-acetyl-beta-glucosidase (NAG) and urinary albumin
      excretion rate (UAER) in morning and 24 h urine were measured. RESULTS: Compared
      to the control group, the levels of alpha1-MG, beta2-MG, NAG, UAER in observation
      group were increased significantly (P < 0.05). beta2-MG, NAG, UAER of Soldiers
      with more than 50 motorized hours in observation group were significantly higher
      than those of control group (P < 0.05). beta2-MG, NAG and UAER of soldiers
      divorced from tank occupation more than 3 years decreased to the normal levels.
      beta2-MG of soldiers divorced from tank occupation more than 10 years was
      significantly higher than that of 6-10 years group. CONCLUSION: Tank occupational
      exposure influences the renal function of tank crews but not to a degree of
      clinical kidney disease. The renal function of crews divorced from tank
      occupation may recover but dysfunction of renal tubular reabsorption still
      exists.

PMID- 25571649
TI  - [Diagnosis and treatment of lumbar spondylolisthesis and lumbar instability].

PMID- 25571651
TI  - [Three vertebral reduction and fixation for revision of lumbar
      spondylolisthesis].
AB  - OBJECTIVE: To analyze the surgical failure of lumbar spondylolisthesis and
      investigate the clinical effect of three vertebral reduction and fixation in
      revision of lumbar spondylolisthesis. METHODS: The clinical data of 19 patients
      underwent revision to lumbar spondylolisthesis was retrospectively analyzed
      between January 2009 and December 2012. There were 12 males and 7 females, aged
      from 36 to 68 years old with an average of 51.5 years. Reduction loss of olisthy
      segment had in 6 cases, internal fixation loosening or breakage had in 5 cases,
      slippage aggravating had in 8 cases. Clinical symptoms including lower back pain,
      unilateral or bilateral lower extremity pain and numbness, etc. Revision surgery
      was performed with three vertebral pedicle screw internal fixation and posterior
      decompression, reduction, and posterolateral bone graft between vertebral body.
      For the first time after surgery pedicle screw loosening or fracture of vertebral
      body, to switch thick or long pedicle screws implanted into again, or with bone
      cement perfusion and implanted with pedicle. The condition of intervertebral
      fusion and clinical effect were respectively assessed by X-ray films and JOA
      score. RESULTS: All patients were followed up from 10 to 30 months with an
      average of 18 months. X-ray showed all bone graft obtained fusion and fusion time
      was from 5.5 to 7 months after revision. No pedicle screws loosening and breakage
      were found and no reduction loss vertebral body. JOA score were statistically
      analyzed between preoperative and postoperative at 6 months, in 3 cases with
      degree I, the score respectively was 13.33 +/- 1.53 and 26.33 +/- 0.58; in 7
      cases with degree II, the score respectively was 12.85 +/- 2.19 and 26.29 +/-
      2.21; in 9 cases with degree III, the score respectively was 12.21 +/- 2.73 and
      26.44 +/- 1.81; there was statistical significance between preoperative and
      postoperative at 6 months, the improvement rate of JOA was (78.06 +/- 3.90)%.
      CONCLUSION: For the patients with lumbar spondylolisthesis, the reason of primary
      surgical failure mainly concerned with internal fixation loosening and breakage,
      and bone graft no-fusion. Revision surgery using three vertebral pedicle screw
      internal fixation, can get rigid fixation, complete decompression, bone graft
      fusion, combined with the guidance of the postoperative functional exercise for
      patients, can obtain satisfactory therapeutic effects.

PMID- 25571650
TI  - [Unilateral pedicle screw fixation and transforaminal lumbar interbody fusion
      through paraspinal muscle approach for recurrent lumbar disc herniation combined
      with lumbar instability].
AB  - OBJECTIVE: To explore the clinical effects of unilateral pedicle screw fixation
      and transforaminal lumbar interbody fusion (TLIF) through paraspinal muscle
      approach for recurrent lumbar disc herniation combined with lumbar instability.
      METHODS: A total of 35 patients with recurrent lumbar disc herniation combined
      with lumbar instability were treated between March 2008 and May 2010, including
      15 patients managed by the paraspinal muscle approach with unilateral pedicle
      screw fixation and transforaminal lumbar interbody fusion (TLIF) (unilateral
      fixation group) and 20 patients by the posterior midline approach with bilateral
      pedicle screw fixation and posterior lumbar interbody fusion (bilateral fixation
      group). Operation time and intraoperative blood loss were observed, preoperative
      and postoperative JOA score and VAS score in low back pain and legs pain, the
      interbody fusion condition were compared between two groups. RESULTS: All
      patients were followed up from 6 to 30 months with an average 16.8 months. All
      clinical symptoms had obviously improved postoperatively. X-rays showed good
      interbody fusion (only 1 case did not obtain fusion in bilateral fixation group)
      without cage displacement or settlement and implant loosening or breakage. There
      was significant difference in operation time and the intraoperative blood loss
      between two groups (P < 0.05). Postoperative JOA score had obviously decreased
      than preoperative one (P < 0.05). At 1 week after surgery, there was significant
      difference in VAS score of low back pain between two groups and there was no
      significant difference in VAS score of legs pain between two groups (P > 0.05);
      at final follow-up, there was no significant difference in VAS score of low back
      pain and legs pain between two groups (P > 0.05). CONCLUSION: Two methods both
      can obtain satisfactory effect in treating recurrent lumbar disc herniation
      combined with lumbar instability. Through the paraspinal muscle approach with
      unilateral pedicle screw fixation and TLIF has advantages of smaller surgical
      incision, shorter operation time, less intraoperative blood loss, faster relief
      in low back pain after operation, etc.

PMID- 25571652
TI  - [Treatment of lumbar instability with transforaminal lumbar interbody fusion
      (with single cage) combined with unilateral pedicle screw fixation].
AB  - OBJECTIVE: To explore the clinical effect of transforaminal lumbar interbody
      fusion (with single cage) combined with unilateral pedicle screw fixation in
      treating lumbar instability. METHODS: The clinical data of 50 patients with
      lumbar instability were retrospectively analyzed. They underwent treatment and
      obtained following up more than 8 months from 2009 to 2012. All patients
      complicated with refractory or recurrent lower back pain, and unilateral
      primarily or unilateral lower limb radiation pain, X-ray and CT films showed
      lumbar instability. The patients were respectively treated with transforaminal
      lumbar interbody fusion (with single cage) combined with unilateral or bilateral
      pedicle screw fixation. According to different fixation methods, they divided
      into unilateral fixation group and bilateral fixation group. There were 20
      patients with 22 intervertebral spaces in unilateral fixation group, 8 males and
      12 females, aged from 26 to 66 years old, 2 cases with isthmic spondylolisthesis
      of degree I, 8 cases with degenerative spondylolisthesis, 10 cases with lumbar
      disc herniation; fusion location with L3,4 was in 1 case, L4,5 was in 12 cases,
      L5S1 was in 9 cases. There were 30 patients with 30 intervertebral spaces in
      bilateral fixation group, 14 males and 16 females, aged from 41 to 62 years old,
      4 cases with isthmic spondylolisthesis of degree I,14 cases with degenerative
      spondylolisthesis, 12 cases with lumbar disc herniation; fusion location with
      L3,4 was in 3 cases, L4,5 was in 15 case, L5S1 was in 12 cases. Operation time,
      intraoperative blood loss, postoperative drainage, complications were analyzed
      and intervertebral height, lordosis angle changes, fusion rate and clinical
      effect were compared between two groups. RESULTS: All incisions obtained primary
      healing,lower limb radiation pain and low back pain disappeared basically, no
      infection, endorachis injury was found. Foot drop occurred in one case of
      bilateral fixation group and no iatrogenic neurological symptom was found in
      unilateral fixation group. All patients were followed up from 8 to 18 months with
      an average of (10.8?4.3)months. Ac- cording to JOA score improvement rate (RIS)
      to assess clinical effect, all patients got excellent and good results, there was
      no statistically significant difference between two groups. Two methods can both
      effectively increase the pathological intervertebral height. Unilateral fixation
      group was better than bilateral fixation group in aspect of operation time,
      intraoperative blood loss and postoperative drainage. CONCLUSION: With strict
      indication and good skills, transforaminal lumbar interbody fusion (with single
      cage) combined with unilateral pedicle screw fixation in treating lumbar
      instability has advantages of smaller traumatic, less blood loss, faster recovery
      for the patient and can reduce the economic cost.

PMID- 25571653
TI  - [Effect of reduction on spino-pelvic parameters in treating high-grade lumbar
      spondylolisthesis].
AB  - OBJECTIVE: To explore the effect of reduction on spino-pelvic balance in treating
      high-grade lumbar spondylolisthesis. METHODS: From Augest 2008 to Augest 2011,
      the data of 16 patients with high-grade lumbar spodylolisthesis (Meyerding grade
      III or more than grade III) underwent reduction treatment through posterior
      approach were retrospectively analyzed. There were 9 males and 7 females, aged
      from 24 to 65 years old with an average of 44 years. Preoperative, postoperative
      at 2 weeks and final follow-up, spino-pelvic parameters of all patients were
      measured and compared by total legth lateral X-rays, and spino-pelvic parameters
      included sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), lumbar
      lordosis (LL) and sagittal vertical axis (SVA); the informations of
      intervertebral bone fusion was observed by CT and postoperative complications
      were recorded; clinical effects were assessed according to clinical Oswestry
      score (CODI). RESULTS: All patients were followed up from 12 to 24 months with an
      average of 18 months. Four cases reduced anatomically, 8 cases reduced to grade I
      .4 cases reduced to grade II. There was statistically significant differences in
      sacral slope (SS), pelvic tilt (PT), lumbar lordosis angle (LL) and sagittal
      vertical axis (SVA) between before operation and two weeks after operation (P <
      0.05), while pelvic incidence (PI) no statistically significant differences was
      found between before operation and two weeks after operation (P > 0.05). There
      was no statistically significant differences in SS, PT, LL, SVA, PI between two
      weeks after operation and final follow-up (P > 0.05). CODI had decreased from
      preoperative 36.6 +/- 4.2 to 14.7 +/- 4.0 at final follow-up (P < 0.05). One year
      after operation, all patients obtained bone fusion and can find the union of bone
      trabeculae by three-dimensional reconstruction CT. Three cases occurred transient
      nerve root pain, and recovered after medicinal treatment. No infection and
      internal fixation loosening and breakage were found. CONCLUSION: Surgical
      reduction for high-grade lumbar spondylolisthesis can improve spino-pelvic
      balance and acquire satisfactory outcomes.

PMID- 25571654
TI  - [Analysis of the reason of secondary fracture after percutaneous vertebroplasty
      for osteoporotic vertebral compression fractures].
AB  - OBJECTIVE: To explore the reasons of secondary fracture after percutaneous
      vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCFs) and
      discuss the measure of prevention and cure. METHODS: From January 2011 to January
      2013, the clinical data of 180 patients with primary OVCFs treated by PVP were
      retrospectively analyzed. There were 75 males and 105 females, aged from 68 to 95
      years old with an average of (79.50 +/- 5.45) years. The involved vertebrae were
      identified according to the clinical symptoms and imaging data. PVP were
      performed in 362 vertebrae and the patients were followed up with an average of
      12 months. Subsequent vertebral fractures were found through the pain's
      reappearance and MRI or bone scan. The patients were divided into secondary
      fracture group and no-secondary fracture group according to the subsequent
      fractures or no. Secondary fracture group was divided into two groups according
      to gender, and the patients with secondary fracture were also categorized into
      the original surgical vertebral fractures, adjacent vertebral fracture and remote
      vertebral fractures. The age, gender, the cement volume, the cement leakage,
      secondary fracture site, the incidence and type of secondary fracture were
      observed and compared among different groups. RESULTS: Among the 362 vertebrae of
      PVP, there were 109 vertebrae in male and 253 vertebrae in female. And 27
      vertebrae (10 in male and 17 in female) of 22 cases (9 males and 13 females)
      occurred secondary fracture. The second PVP were performed in 13 cases (16
      vertebrae) and the third PVP in 2 cases (4 vertebrae); 7 cases (7 vertebrae) were
      treated with conservative therapy. There was no statistically significant
      difference on age, gender, cement volume and leakage between secondary fracture
      group and no-secondary fracture group (P > 0.05). There was no statistically
      significant difference on the incidence and type of secondary fracture between
      male and female (P > 0.05). No significant difference was found on the adjacent
      and remote vertebral fractures (P > 0.05). Most of secondary fracture occurred in
      6 months, and whether the single and double side injection, cement leakage had no
      obvious relation. CONCLUSION: There is no significant difference in the
      subsequent fracture after PVP for the OVCFs different gender and fractured site,
      and also no significant difference in the adjacent and remote vertebral
      fractures. The report didn't support the biomechanical viewpoint that vertebral
      body stiffness increasing after PVP would lead to adjacent vertebral stress
      increasing and result easily in adjacent vertebral fracture. Secondary fracture
      occurs always in 6 months after operation, which is the natural course of
      osteoporosis.

PMID- 25571655
TI  - [Case-control study on intrasacrospinal muscular approach and posterior midline
      approach for the treatment of far lateral lumbar disc herniation].
AB  - OBJECTIVE: To compare the clinical outcomes of intrasacrospinal muscular approach
      and posterior midline approach in treating far lateral lumbar disc herniation.
      METHODS: The clinical data of 32 patients with far lateral lumbar disc herniation
      underwent transforaminal lumbar interbody fusion from January 2004 to January
      2011 were retrospectively analyzed. The patients were divided into
      intrasacrospinal muscular approach group (11 males and 6 females ) and posterior
      midline approach group (10 males and 5 females). All patients were followed up
      from 12 to 18 months with an average of 15.3 months. Operative time, blood loss,
      postoperative draining volume were recorded and pre-and post-operative visual
      analog scale (VAS) and Oswestry Disability Index (ODI) were compared between two
      groups. RESULTS: Operative time, blood loss, postoperative draining volume in
      intrasacrospinal muscular approach group was less than that of posterior midline
      approach group (P < 0.05). There was no significant difference in VAS at final
      follow-up between two groups (P > 0.05); and the mean ODI in intrasacrospinal
      muscular approach group was less than that of posterior midline approach group (P
      < 0.05). CONCLUSION: For the treatment of far lateral lumbar disc herniation,
      intrasacrospinal muscular approach has less injury for paraspinal muscle and more
      satisfactory clinical outcome and is better method than posterior midline
      approach.

PMID- 25571656
TI  - [The clinical value of end plate rings in preventing subsidence of titanium cage
      in anterior cervical corpectomy and fusion surgery].
AB  - OBJECTIVE: To evaluate the clinical results of using end plate rings in
      preventing subsidence of titanium cage in anterior cervical corpectomy and fusion
      (ACCF) surgery. METHODS: The clinical data of 71 patients with cervical
      spondylotic myelopathy underwent ACCF in single segment from February 2008 to
      February 2011 were retrospectively analyzed. There were 38 males and 33 females,
      aged from 39 to 74 years old with a mean of 53.8 years. Thirty-three were used
      end plate rings and thirty-eight were not used (end plate rings group and no end
      plate ring group, respectively). The Japanese Orthopaedic Association (JOA)
      score, Odom's scale, imaging data were used to evaluate the clinical effects.
      Imaging data including Cobb angle of fusion segment, intervertebral height of
      anterior border (Da) and posterior border (Dp), the mean intervertebral height
      (Dm). RESULTS: All patients were followed up from 13 to 34 months with an average
      of 19.5 months. Between two groups, there was no significant difference in Cobb
      angle of fusion segment and the mean intervertebral height (Dm) before surgery
      and one week after surgery. Whereas, one year after surgery, the Cobb angle of
      end plate ring group was (9.4 +/- 3.8) degrees, and contral group was (7.5 +/-
      3.9) degrees, which was significantly lower than that of end plate ring group.
      Meanwhile, the Dm of end plate ring group was (57.3 +/- 2.2) mm, and no end ring
      group was (55.2 +/- 2.6) mm which was significantly lower than that of end plate
      ring group. The subsidence in end plate ring group was 57.6%, and was 78.9% in no
      end plate ring group. There was no significant difference in JOA score before and
      after surgery between two groups. At 1 year after operation, 90.9% (30/33) got
      excellent or good results in end plate ring group, 89.5% (33/38) got excellent or
      good results in contral group. CONCLUSION: The use of end plate rings could not
      completely prevent the subsidence of titanium cage, however, which can decrease
      the occurrence rate of the subsidence and lessen its degree.

PMID- 25571657
TI  - [Comparison of clinical effects of total spondylectomy with different procedures
      in treating lumbar metastatic tumor].
AB  - OBJECTIVE: To compare the therapeutic effects of debris spondylectomy, piecemeal
      spondylectomy, total en bloc spomdylectomy in treating lumbar metastatic tumors.
      METHODS: The clinical data of 20 patients with lumbar metastatic tumors treated
      from January 2008 to October 2013 were retrospectively reviewed. There were 8
      males and 12 females, aged from 35 to 65 years old with an average of (49.50 +/-
      9.97) years. All patients had single solitary metastases. Four cases were in L1,5
      cases in L2,4 cases in L3,4 cases in L4, and 3 cases in L5. According to the type
      of Tomita, type II had in 4 cases, type III in 6 cases, type IV in 6 cases, type
      V in 4 cases. Tokuhashi score was 12.50 +/- 1.97. All patients complained with
      back or leg pain, VAS score was 8.13 +/- 0.85. Among patients, 7 cases were
      treated with debris spondylectomy (group A), 7 cases with piecemeal spondylectomy
      (group B), 6 cases with total en bloc spondylectomy (group C). Statistical
      analysis was used to compare the three groups with respect to surgical trauma
      (including operative time, transoperative bleeding, and intraoperative blood
      transfusion), clinical symptoms (by VAS score at 1 week after operation),
      surgical procedures conditions (by AP and lateral X-rays), and long-term results
      (by recurrence and death information). RESULTS: All patients were followed up
      from 6 to 36 months with an average of (16.50 +/- 7.88) months. Operative time
      for debris spondylectomy was (6.14 +/- 0.68) h, intraoperative bleeding was (3
      457.14 +/- 399.40) ml, and intraoperative blood transfusion was (2 771.43 +/-
      423.14) ml. Operative time for piece-meal spondylectomy was (4.93 +/- 0.61) h,
      intraoperative bleeding was (1 942.86 +/- 378.51) ml, and intraoperative blood
      transfusion was (1 500.00 +/- 336.65) ml. Operative time for total en bloc
      spondylectomy was(4.17 +/- 0.67) h, intraoperative bleeding was (1 341.67 +/-
      361.13) ml, and intraoperative blood transfusion was (916.67 +/- 321.66) ml.
      There was significant differences in operative time, intraoperative blood loss,
      and intraoperative blood transfusion between three groups (P < 0.05). In terms of
      these factors, total en bloc spondylectomy had the best outcome followed by
      piecemeal spondylectomy. All pains had released, VAS score decreased obviously at
      1 week after operation (P < 0.05), and there was no significant differences
      between three groups (P > 0.05). Surgical effects were well with these methods
      according to the evaluation of AP and lateral X-rays . At final follow-up, group
      A had 4 recurrences (2 with breast cancer, 1 with prostate cancer,and 1 with
      thyroid cancer) and 3 deaths (2 with lung cancer and 1 with thyroid cancer);
      group B had 2 recurrences (1 with breast cancer and 1 with prostate cancer) and 3
      deaths (1 with lung cancer, 1 with breast cancer and 1 with kidney cancer);group
      C had no recurrences and 2 deaths for lung cancer. There was significant
      differences in recurrence and death between three groups (P < 0.05). In terms of
      these factors, total en bloc spondylectomy had the best outcome in three methods.
      CONCLUSION: Three kinds of operation method can relieve pain, improve nerve
      function, increase the spinal stability, control the local lesions, improve the
      patient's quality of life in treating lumbar metastatic tumors, but total en bloc
      spendylectomy, respect to operative time, transoperative bleeding, intraoperative
      blood transfusion, tumor recurrence and death is clearly superior to other two
      methods.

PMID- 25571658
TI  - [Intertransverse approach microendoscopic discectomy for far lateral lumbar disc
      herniation].
AB  - OBJECTIVE: To explore the clinical effect of intertransverse approach
      microendoscopic discectomy for far lateral lumbar disc herniation. METHODS: From
      February 2005 to February 2010, 73 patients with far lateral lumbar disc
      herniation were treated with intertransverse approach microendoscopic discectomy.
      Their clinical data were retrospectively analyzed. There were 41 males and 32
      females, aged from 19 to 80 years old with an average of 56.5 years; courses of
      disease ranged from 1 to 25 months with an average of 4.5 months. The main
      symptom was low back pain and sciatica, especially the sciatica was seriously.
      Herniation level was in L3,4 of 9 cases, L4,5 of 49 cases, L5S1 of 15 cases.
      Preoperative, 2 weeks after operation, final follow-up, conditions of pain relief
      were assessed by visual analogue scale (VAS); total life quality of patients were
      evaluated by Oswestry Disability Index (ODI) before operation and last follow-up.
      RESULTS: All operations were performed successfully, operative time was from 40
      to 115 min (mean of 50 min); and blood loss was from 50 to 150 ml (mean of 110
      ml). Incision infection had 1 case and incomplete nerve root injury had 1 case.
      All patients were followed up from 3 to 8 years with an average of 4.5 years.
      Postoperative VAS and ODI had obviously improved (P < 0.01). CONCLUSION: The
      technique of intertransverse approach microendoscopic discectomy is a feasible
      and effective method for far lateral lumbar disc herniation.

PMID- 25571659
TI  - [Effects of artificial disc replacement with angles on stress of adjacent
      intervertebral disc].
AB  - OBJECTIVE: To evaluate stress changes of intervertebral space and adjacent
      intervertebral space after artificial disc replacement with angles. METHODS:
      Artificial disc replacement with angles were designed according to existing data.
      Axial pressure, flexion/extension, lateral bending and torsion loading were
      applied on finite element models of normal cervical discs on C4,5 segments, C4,5
      segments with 0 degrees artificial cervical discs and C4,5 segments with 10
      degrees artificial cervical discs, then stress changes of C4,5 space was
      observed. The same loadings were applied on finite element models of normal
      cervical discs on C4-C6 segments, C4,5 segments with 0 degrees, C4,5 segments
      with 10 degrees, then stress changes of replaced segments space and adjacent
      segment space were observed. RESULTS: For C4,5 segments, 80 MPa/0 degrees
      artificial discs and 80 MPa/10 degrees artificial discs had the similar
      equivalent shear stress (Se), and were both larger than that of normal discs,
      when lateral bending were performed, 80 MPa/0 degrees artificial discs were
      closed to normal discs when axial pressure and flexion/extension were carried
      out, while 80 MPa/10 degrees artificial discs had a larger Se than that of normal
      ones,when torsion loading were applied, Szx/Szy stress of 80 MPa/0 degrees and 80
      MPa/10 degrees artificial discs were closed to normal ones. For C4-C6 segments,
      the axial pressure, flexion/extension and lateral bending of C5,6 were all lower
      than normal discs after C4,5 discs were replaced by 80 MPa/10 degrees artificial
      discs, while Szx/Szy of torsion loading were closed to normal ones. CONCLUSION:
      Artificial discs with 10 degrees have less influences on stress of adjacent
      intervertebral space and closer to mechanical property after being implanted into
      intervertebral space.

PMID- 25571660
TI  - [Treatment of atlanto-axial vertebral instability fractures with cervical
      posterior pedicle screw internal fixation and interbody fusion].
AB  - OBJECTIVE: To explore the clinical effects of cervical posterior pedicle screw
      internal fixation and interbody fusion for the treatment of atlanto-axial
      vertebral instability fractures. METHODS: From July 2008 to July 2013, 21
      patients with atlanto-axial vertebral instability fractures were treated with
      vertebral pedicle screw internal fixation and interbody fusion through posterior
      approach. There were 14 males and 7 females, aged from 20 to 55 years old with an
      average of 32 years. Lifted and guided the atlanto-axial vertebral pedicle screw
      to reduce atlanto-axial vertebral displacement. RESULTS: All patients were
      followed up from 6 to 24 months with an average of 12.5 months. Wounds got healed
      without complication of infection. Clinical symptoms were relieved at 6 months
      after operation. According to ASIA score standard to assess at 6 months after
      operation, the items of motion, light touch and needle score had obviously
      improved, and respectively were 99.45 +/-0.27, 111.09 +/- 0.47,111.11 +/- 0.58.
      VAS and NDI scores also had obviously improved, and respectively were 1.04 +/-
      0.38 and 12.56 +/- 2.24. Imaging examinations showed internal fixation locations
      were good, without atlanto-axial joint instability. CONCLUSION: Cervical
      posterior pedicle screw internal fixation and interbody fusion can effectively
      restore the stability of atlanto-axial joint, reduce complication and obtain
      satisfactory effects.

PMID- 25571662
TI  - [Anatomical study on vertebral artety and its application in transpedicle screw
      fixation for upper cervical vetebrae].
AB  - OBJECTIVE: To investigate the relationship of upper cervical pedicle and
      vertebral artery (VA) location in order to improve the safety of transpedicular
      screw insertion. METHODS: The vertebral arteries on 12 sides of 6 adult pate
      cadaverous specimens were dissected. The distance between VA and VA groove at the
      atlas needling point of transpedicle screw, and the distance between VA and the
      inner edge of axis cervical foramen, and the VA external diameter in axis
      cervical foramen were measured respectively. RESULTS: The distance between VA and
      VA groove was (1.96 +/- 0.72) mm on the left and (1.99 +/- 0.61)mm on the right
      at the atlas needling point of transpedicle screw, the distance between VA and
      the inner edge of axis cervical foramen was (2.23 +/- 0.43) mm on the left and
      (2.30 +/- 0.39) mm on the right, the VA external diameter in axis cervical
      foramen was (3.03 +/- 0.48) mm on the left and (2.98 +/- 0.75) mm on the right.
      CONCLUSION: It is unlikely to injury VA when the transpedicle screws of upper
      cervical vertebrae were implanted correctly besides high straddled VA, and the
      individualization must be performed in the process.

PMID- 25571661
TI  - [Effects and mechanism of low-intensity pulsed ultrasound on extracellular matrix
      in rabbit knee osteoarthritis].
AB  - OBJECTIVE: To observe the effects of low-intensity pulsed ultrasound (LIPUS) on
      repairing extracellular matrix in rabbit knee osteoarthritis and analyze its
      mechanism. METHODS: Sixty adult female rabbits with an average weight of (2.0 +/-
      0.2) kg, were divided randomly into two groups (experimental group and control
      group, 30 rabbits in each group). All rabbits were replicated in right knees by
      Hulth method for knee osteoarthritis model. Two weeks after operation, the
      rabbits in experimental group were treated with LIPUS, and the ultrasonic
      frequency was (800 +/- 5%)KHz and the maximum intensities of spatially averaged
      and time averaged (SATA) was (50 +/- 10%) mw/cm2, for 1 time a day and every time
      20 min, while the rabbits in control group were treated with sham LIPUS,the same
      operation with experimental group but without energy output. At the 2, 4, 8 weeks
      after treatment, 10 rabbits in each group were randomly killed for each time. The
      general changes of cartilage and its histopathological changes by HE staining
      were observed; the expression of collagen type II, proteoglycan, MMP-3, 7, 13 in
      cartilage were analyzed by immunohistochemical and RT-PCR technique; and the
      expression of NO in cartilage was analyzed by nitrate reduction method. RESULTS:
      On the same observed time point, the damage degree of cartilage in experimental
      group was slighter than that of control group (P < 0.01), the expression of MMP
      3, 7, 13 and NO in cartilage in experimental group was lower than that of control
      group (P < 0.01) while collagen type II and proteoglycan was higher than that of
      control group (P < 0.01). CONCLUSION: Low-intensity pulsed ultrasound can repair
      the damaged cartilage by reducing the expression of MMP-3, 7, 13, inhibiting the
      secretion of NO and promoting the synthesis of collagen type II and proteoglycan
      in cartilage.

PMID- 25571663
TI  - [Repair of-limb soft tissue defect with free deep inferior epigastric perforator
      flap].
AB  - OBJECTIVE: To report the clinical application results of free deep inferior
      epigastric perforator flap in the repair of soft tissue defect. METHODS: From
      January 2006 to January 2012,13 patients with soft tissue defect (7 cases in leg
      and 6 cases in forearm) underwent reconstruction with a free deep inferior
      epigastric perforator flap. There were 9 males and 4 females, aged from 21 to 45
      years old with an average of 33 years. Soft tissue defect in the extremities were
      from 7 cm x 17 cm to 8 cm x 26 cm. The medial branch and lateral brangh flaps
      were 7 cases and 6 cases respectively. The donor site was closed directly.
      RESULTS: One patient developed small wound dehiscence, which spontaneous healed
      at one month after surgery. All the flaps had survived completely. Follow-up
      period ranged from 1.8 to 4.0 years with the mean of 2.8 years postoperatively.
      Satisfactory clinical results were obtained in 12 cases. A good contour was
      confirmed at the recipient area. CONCLUSION: The free deep inferior epigastric
      perforator flap for the extremities defects of soft tissue is a good option. This
      technique is safe and reliable, and can decrease the injury of donor site.

PMID- 25571664
TI  - [Clinical application of free vascularized flaps based on the wrist cutaneous
      branch of ulnar artery in repairing finger soft tissue defect].
AB  - OBJECTIVE: To investigate the methods and clinical effects of repairing finger
      soft tissue defect with free vascularized flaps based on the wrist cutaneous
      branch of ulnar artery. METHODS: From February 2010 to December 2012, 16 patients
      with finger soft tissue defects were repaired by free vascularized flaps based on
      the wrist cutaneous branch of ulnar artery, including 10 males and 6 females with
      an average age of 38.2 years old ranging from 18 to 52 years. Among them, 5 cases
      caused by hot crush injury, 8 cases caused by machine crush injury, 3 cases
      caused by firecracker burst injury. The defect area varied from 1.3 cm x 2.3 cm
      to 2.6 cm x 5.0 cm. The flap area varied from 1.5 cm x 2.5 cm to 2.8 cm x 5.2 cm.
      The appearance and two-point discrimination of flap were observed after
      operation. RESULTS: All flaps survived and wounds healed primarily. No wound
      infection and skin necrosis were found in donor site and recipient site. Among
      repair methods, direct suture in forearm donor site had 11 cases and skin graft
      had 5 cases. All patients were followed up from 6 to 24 months with an average of
      10.8 months. The appearance of flap was not fat or clumsy, texture and color were
      similar to the recipient site, the sensation were good, two-point discrimination
      was 6 to 9 mm. The appearance of donor site were well complicated with mild
      scarring without dysfunction obviously. CONCLUSION: The free vascularized flaps
      based on the wrist cutaneous branch of ulnar artery has the advantages of
      vascular anatomy constant,thickness moderate and carry sensory nerves, etc, which
      is effective way to repair finger soft tissue defects.

PMID- 25571665
TI  - [Hip arthroplasty for the severe comminuted proximal femoral fracture with
      psilateral acetabulum fracture].
AB  - OBJECTIVE: To investigate the results of hip arthroplasty for the treatment of
      severe comminuted proximal femoral fracture with ipsilateral acetabulum fracture.
      METHODS: From June 2007 to September 2013, 8 patients (8 hips) with severe
      comminuted proximal femoral fracture combined with ipsilateral acetabulum
      fracture were treated with hip arthroplasty. All patients were male and using
      biological prosthesis. Aged from 33 to 64 years old with an average of 41.9
      years. According to Harris score in aspect of pain, function, range of motion to
      evaluate clinical effects. RESULTS: There was no untoward reaction in 8 patients.
      And bed rest at 3 months after operation, waiting for acetabulum fracture healed
      to out-of-bed activity. There was no complications such as pneumonia, bedsore and
      so on in the patients. Follow-up time was from 9 to 72 months with an average of
      35.8 months, the wound healed, there was no the subsidence and loosening of
      prosthesis, no dislocation and infection. The mean of Harris score was 87.5
      points after operation. CONCLUSION: The effect of the hip replacement in treating
      severe comminuted proximal femoral fracture with ipsilateral acetabulum fracture
      is confirmed. It can restore motor function and reduce traumatic complication,
      may serve as a substitute for internal fixation of difficult operation. The long
      term efficacy is necessary to further observe.

PMID- 25571666
TI  - [Delayed paralysis of limbs caused by anterior cervical operation: a case
      report].

PMID- 25571667
TI  - [Progress on osteochondritis dissecans].
AB  - Along with the popularity of youth movement, the incidence of osteochondritis
      dissecans (OCD) showed a trend of increase, but its pathogenesis is not yet
      clear. Previous studies suggested that trauma is the main potential cause, but
      with the emergence of vast family cases, hereditary factor is also gradually
      taken seriously. Arthroscopy is the "gold standard" for diagnosing OCD, but for
      the patient with early incomplete joint surface lesions, the diagnositic value of
      MRI is better than the arthroscopy. For the patients with stable form OCD,
      nonoperative management should be used such as adjusting activity, fixator and
      drugs; for the patient with unstable form OCD or failing after conservative
      treatment, surgery should be generally used such as joint clearing, drilling,
      microfracture method, fixation and transplantation. With the progress of
      research, stem cell technology and platelet-rich plasma gradually applied in
      cartilage repair, which will improve the curative effect of OCD, but still
      further clinical and experimental research, and also a long-term effective follow
      up are needed.

PMID- 25571668
TI  - [Progress on cervical spondylosis in youths].
AB  - Cervial spondylosis is one of the most common orthopedic diseases. But in recent
      years, onset age of cervical spondylosis becomes more and more younger, which not
      only cause serious physical and psychological pain on the patients, but also
      cause a series of social problems. The occurrence of youth cervical spondylosis
      caused by cervical bad learning work posture for a long time, but psychological
      factors cannot be igored. The disease belongs to the early stage of cervical
      spondylosis in fact, which results from power imbalance of neck muscle. Clinical
      symptom is given priority to with neck shoulder pain and discomfort, often show
      the cervical physiological curvature change on imaging and cervical instability.
      Prevention and treatment of youth cervical spondylosis should mainly focus on
      prevention. Comprehensive treatment should be provided as soon as possible after
      the clinical diagnosis of the disease in order to prevent the illness even worse.
      Conservative treatment is often applied, and the neck rehabilitation training
      cannot be ignored at the same time. It's necessary to further study about the
      pathogenesis of cervical spondylosis, which will help to enhance the
      understanding of the disease and better to guide the treatment. The review aims
      to make a conclusion about advancement in cervical spondylosis in youths in
      aspects of etiology, pathogenesis, clinical characteristics and treatment.

PMID- 25571669
TI  - Ergometric performance and cardiovascular profile of obesity clinic patients.
AB  - BACKGROUND: Aerobic exercise capacity is considered as an independent prognostic
      factor for cardiovascular disease and mortality. It is usually expressed in
      maximal oxygen consumption (VO2(max)) or metabolic equivalent (MET) and is
      measured by spiroergometry or calculated by a regression formula based on maximal
      performance achieved. Obesity is associated with reduced physical performance and
      increased cardiovascular mortality. The aim of our study was to describe the
      ergometric and cardiovascular profile of patients of an obesity clinic, and to
      compare a direct measure of VO2(max) with an indirect by a regression formula and
      to. METHOD: 131 consecutive patients of an obesity clinic (95 females, 36 males)
      aged 16-75 years participated. The VO2(max) was measured by spiro-ergometry on a
      treadmill and estimated by a regression formula on the basis of the speed and
      grade of the treadmill. We have determined the relationship between Body mass
      index (BMI), Waist Circumference (WC) and the parameters VO2(max)/kg, MET,
      Performance Relative for Age, Heart Rate Recovery one minute after maximal effort
      (HRR), VO2(max) relative to a theoretical normal body weight (corresponding to a
      BMI of 25 kg/m2 (VO2(max)Rel25)), blood pressure, at rest and 5 minutes after
      exercise, Framingham Score and C-reactive protein (CRP). RESULTS: For the
      different age groups the VO2(max)/kg was below normal values (mean -23.4%).
      Measured VO2(max) was 15.2% lower than estimated by the regression formula. After
      adjusting to age and to a theoretical upper-limit normal body weight
      (corresponding to a BMI of 25 kg/m2) VO2(max)/kg was 5-20% (mean value 15%)
      higher than the reference values. VO2(max)/kg and HRR were correlated with BMI,
      WC and Framingham Score. 40% of the patients were already treated for
      hypertension, 55% had elevated blood pressure measurements at rest and 52% after
      exercise. CONCLUSIONS: Ergometric stress testing in obese subjects delivers
      important information that helps to evaluate the cardiovascular risk in this
      population and to provide individual recommendations for training therapy (e.g.
      training intensity, heart rate etc). Obese patients show a marked diminution of
      aerobic exercise capacity. In this population, the use of a standard regression
      formula to calculate VO2(max) leads to an overestimation of aerobic performance.
      The even higher than normal VO2(max) related to upper-normal body weight
      indicates that the reduced physical performance in obese patients is rather due
      to the overweight than to a pathological loss of muscle mass.

PMID- 25571671
TI  - [Felicien M. Steichen. M.D., F.A.C.S. (1926-2011). Portrait of a surgeon].
AB  - The personality and the achievements of Professor Dr. Felicien M. Steichen, who
      was born in Luxembourg (10.13.1926) and died in Brignogan-Plages, France
      (6.27.2011) are brought into focus. His was a most distinguished career devoted
      to surgery, research, teaching and writing in Baltimore, Pittsburgh and New York.
      He will be remembered above all for his contributions to stapling in thoracic and
      abdominal surgery and to minimally invasive surgery.

PMID- 25571670
TI  - Posterior fossa mass in immunosuppressed patient.
AB  - BACKGROUND: Toxoplasmosis is the most frequent opportunistic infection of the
      central nervous system among individuals with the acquired immunodeficiency
      syndrome. Radiographic modalities include brain CT, MRI and PET scan. The
      differential diagnosis are usually: primary CNS lymphoma, cerebral metastasis,
      Progressive multifocal leukoencephalopathy, cytomegalovirus. It indicates severe
      immunodeficiency and, if it remains untreated, it may lead to death. CASE
      DESCRIPTION: A 65 year old immunodeficiency woman with a Non Hodgkin Lymphoma
      treated with Chemotherapy. She had been suffering from vomiting, headache and
      vertigo. Treatment she received Dafalgan, Betaserc, neupogen and nexiam.
      CONCLUSION: This case illustrates that a brain biopsy is compulsory before
      starting any treatment.

PMID- 25571672
TI  - Moderate to severe injuries in football: a one-year prospective study of twenty
      four female and male amateur teams.
AB  - This study aimed to realize a prospective follow-up of the injuries occurring in
      female and male football players involved in the highest league in the Grand
      Duchy of Luxembourg. Data concerning anthropometric characteristics and football
      activities were gathered in 125 female and 243 male football players via
      questionnaires at the beginning of the study. Then, a follow-up of moderate to
      severe injuries (> 15 days of interruption in football practice) was performed
      throughout the season 2013-2014. Sixteen injuries (injury incidence = 0.7
      injuries/1000 h of exposure) were observed in 13 female football players (10.4%).
      These injuries concerned mainly the knee (n = 7; 43.7%), with capsules and
      ligaments being the most often concerned tissues (n = 7; 43.7%). In male football
      players, 41 severe injuries (injury incidence = 0.6 injuries/1000 h of exposure)
      were observed in 36 players (14.8%). These injuries concerned mainly the thighs
      (n = 12; 29.3%) and the muscles and tendons were the most often concerned tissues
      (n = 18; 43.9%). Injuries in football are predominantly located at the lower
      limbs, particularly the knees in female football players. The predominant muscle
      and tendon lesions of the thighs occurring in males could reveal that physical
      preparation is insufficient or inadequate for a number of players. Regarding
      these results, it is necessary to implement an injury prevention strategy. The
      "FIFA 11+" programme could be used as the basic method, but should be
      personalized according to sex. The injury collection methodology could be
      optimized with the use of an electronic database, such as the Training and Injury
      Prevention Platform for Sports (TIPPS). Beside the systematic recording of injury
      data (as well as the training load) by the players or the medical staff, this
      system allows to share of important information between stakeholders, follow-up
      the players, provide risk factor warnings and increase the awareness of the
      injury problem.

PMID- 25571673
TI  - [Promotion of physical activity for secondary prevention in patients with chronic
      diseases: the situation in the Grand-Duchy of Luxembourg].
AB  - The regular practice of physical activities has health benefits in healthy
      subjects (primary prevention) and in patients with non-communicable diseases
      (secondary prevention). This study aimed to perform a stocktaking of the physical
      activities programs for patients or individuals at risk in the Grand-Duchy of
      Luxembourg. The organizations offering therapeutic physical activities (TPA) have
      been investigated. Eleven groups offering TPA adapted to different non
      communicable diseases were characterized by their costs, instructors,
      participants and potential participants. These groups were divided into five main
      categories: cardiology, neurology, obesity, oncology, and orthopedics. During on
      site meetings, 41 professionals, 192 participants and 34 potential participants
      have been interviewed during the period September 2013 to April 2014. The results
      show that about 40 hours of TPA, 17 hours of which in cardiology, are currently
      proposed every week, except during school holidays. The main TPA are gymnastics,
      aerobics, swimming, Nordic walking, cycling, and resistance training. The
      national coverage is quite low, especially for obesity, neurology and
      orthopedics. The costs is mainly related to the human resources, the gym being
      often borrowed but rarely available during school holidays. Between 200 and 400
      individuals participate in the TPA. The average number of participants per hour
      is 8.9 (+/- 5.1), which represents only 50% of the maximal capacity estimated by
      the instructors (18.0 +/- 8.2 participants per hour). The recruitment process is
      different according to the groups but the medical doctors and the
      physiotherapists are mainly involved in this process. However, the majority of
      the potential participants were not aware of the existence of the groups. The
      existence of these groups is a positive point, since it contributes to compensate
      for the current lack of concrete action of the public and private authorities.
      However, the current TPA offer is clearly insufficient. The groups are frail, on
      the one hand because their future relies exclusively upon the idealism of a few
      key actors, and on the other hand because the participation rate is low. This low
      rate is related to a lack of information and to organizational constraints.
      However, the public health action initiated by these groups should be perpetuated
      and strengthened with a better structuration and professionalization. Finally,
      the increase of the number of participants remains the main objective.

PMID- 25571674
TI  - Hemifacial spasm caused by the cross-compression of the vertebral artery loop--a
      case-centered report of a stitched sling retraction technique.
AB  - Hemifacial spasm (HFS) is one of the neurovascular compression syndromes caused
      by the compression of the facial nerve outgoing from the brainstem by an artery,
      a vein or both. The treatment of choice of this disorder is a microvascular
      decompression (MVD). As initially described, MVD is a technique based on the
      application of the small prostheses that are placed between a cranial nerve and
      an imposing vessel. Neurovascular compression syndromes have relatively high rate
      of incidence. Therefore, many modifications of surgical technique have been
      described in order to minimize the risk of complications and increase the
      effectiveness and permanence of the vascular transposition as the success of the
      MVD most of all depends on the latter. The authors of this paper describe one of
      the aforementioned modifications that provides a complete and permanent vascular
      transposition together with its advantages and limitations in the treatment of
      the hemifacial spasm. Moreover, many aspects of different technical approaches
      are widely discussed and a case-centered stitched sling retraction technique is
      presented.

PMID- 25571675
TI  - Rorschach missing responses--is this more than nothing?
AB  - The Rorschach has been demonstrated as a suitable tool for investigating
      otherwise hidden psychological aspects of sex offenders: sex-related responses
      are more common. The present paper looks at the established tendency of some
      clients to minimise their overall Rorschach responding, the linking of this
      response restraint to particular Rorschach profiles, and the sparse but
      consistent literature which casts doubt on the proposition that Examiner
      enthusiasm will cause the minimising client to provide more responses which
      divulge additional information. In the case of sex offenders, with so much to
      hide, it is proposed that there may be extensive filtering of responses even
      among those giving more than "normal" sex-related responses. "What the client did
      not say", and the corresponding "missing" Rorschach responses in the case of sex
      offenders is discussed in the light of an individual case: (a sex offender with
      undue interest in young boys' penii) where "sex-like" images were specifically
      targeted, but never named as such. The exciting prospect of inferring what the
      client could have said and thus generating the content of missing responses,
      whether or not response filtering produced numerical minimisation, must be
      balanced against the risk of naked men and women (and their genitalia)
      representing nothing more than an artefact of the clinician's own making--"ce qui
      n' est pas le cas".

PMID- 25571676
TI  - The prediction of epidemics through mathematical modeling.
AB  - Mathematical models may be resorted to in an endeavor to predict the development
      of epidemics. The SIR model is one of the applications. Still too approximate,
      the use of statistics awaits more data in order to come closer to reality.

PMID- 25571677
TI  - Tissue engineering in endodontics: root canal revascularization.
AB  - Root canal revascularization attempts to make necrotic tooth alive by the use of
      certain simple clinical protocols. Earlier apexification was the treatment of
      choice for treating and preserving immature permanent teeth that have lost pulp
      vitality. This procedure promoted the formation of apical barrier to seal the
      root canal of immature teeth and nonvital filling materials contained within root
      canal space. However with the success of root canal revascularization to
      regenerate the pulp dentin complex of necrotic immature tooth has made us to
      rethink if apexification is at the beginning of its end. The objective of this
      review is to discuss the new concepts of tissue engineering in endodontics and
      the clinical steps of root canal revascularization.

PMID- 25571678
TI  - Changing demographics and providing dental services for Hispanic children.
AB  - General population demographics in the United States are undergoing dramatic
      changes. Long-term customary populations which provided the bulwark for many
      successful dental practices are being replaced by the many minority populations,
      in particular the Hispanic population. Despite these significant general
      population developments, the demographic profile of the dental profession has
      experienced (and apparently--based on dental student populations--will continue
      to experience) limited changes. The economic strength of the profession may well
      be predicated upon its responses to these developments.

PMID- 25571679
TI  - Does casein phosphopeptid amorphous calcium phosphate provide remineralization on
      white spot lesions and inhibition of Streptococcus mutans?
AB  - OBJECTIVE: The aim of this study was to evaluate the remineralization effect of
      Casein Phosphopeptid Amorphous Calcium Phosphate (CPP-ACP) on white spot lesions
      (WSL) and its inhibitory effect on Streptococcus mutans colonization. STUDY
      DESIGN: The study group consisted of 60 children exhibiting at least 1-WSL.
      Subjects were randomly divided into 2 groups: a test group of using CPP-ACP cream
      (Tooth Mousse, GC Europe N.V., Leuven, Belgium) and a control group using only
      fluoride containing toothpaste for a period of 3-months. 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 sample collection was repeated. Wilcoxon Signed
      Ranks Test was used for statistical analysis. RESULTS: DIAGNOdent measurements
      were increased by time (p = 0.002) in control group and no statistically
      significant diference (p = 0.217) was found in test group by the 3-month period.
      In both groups, the mutans counts were decreased in 3-month experimental period.
      CONCLUSIONS: 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- 25571680
TI  - Direct pulp capping of carious primary molars. A specialty practice based study.
AB  - OBJECTIVE: Recommendations against direct pulp capping (DPC) for carious primary
      teeth are based on old, low level evidence. This study investigates the medium to
      long-term clinical and radiographic outcomes of such treatment. STUDY DESIGN:
      Each of 62 3-9 year old children with any deep, primary molar cavity was included
      if a pulp exposure occurred during caries excavation. Exclusion criteria were
      irreversible pulp damage/uncontrolled hemorrhage. Using rubber-dam, fast setting
      calcium hydroxide (CH) and tooth restoration were placed. Patients were followed
      up for signs/symptoms. Survival analysis, the Kaplan-Meier method and the Mantel
      Cox test were usedfor statistically analyzing the data. RESULTS: Seven patients
      (11.3%) dropped out. Controlled hemorrhage occurred in 25 exposures. Fourteen
      exposures were large and 46 were pin point. Out of 60 primary molars with DPC (in
      55 patients), 7 failed by clinical and/or radiographic criteria. The remaining
      53/60 (88.3%) teeth survived for 21.0 (+/-9.0) months. The 4 year cumulative
      survival rate by Kaplan-Meier analysis was 80%. All restorations remained in
      place with 3 needing replacement without affecting pulp survival. CONCLUSION: The
      CH success rate of carious primary molar DPC justifies further research based on
      careful initial diagnosis ofpulp inflammation reversibility.

PMID- 25571681
TI  - Associations between psychological factors and the presence of deleterious oral
      habits in children and adolescents.
AB  - OBJECTIVES: This study aimed to evaluate the associations between psychological
      factors and the presence of deleterious oral habits in children and adolescents.
      STUDY DESIGN: 147 students aged 8 to 14-years-old were divided in two groups
      concerning the presence and absence of DOH Habit group (HG) and Habit free group
      (HFG). Participants were asked about the presence of DOH using the domain III
      (Oral Habits) of the Nordic Orofacial Test-Screening (NOT-S). Symptoms of anxiety
      and depression were evaluated using the Brazilian Portuguese versions of the
      Revised Children's Manifest Anxiety Scale (RCMAS) and the Children's Depression
      Inventory (CDI), respectively. Saliva was collected 30 min after waking and at
      night to determine the diurnal decline in salivary cortisol (DDSC). Data were
      analyzed using the Chi-squared, Mann-Whitney, Spearman's correlation and logistic
      regression. RESULTS: The prevalence of DOH was higher in females than males (65.1
      vs 34.9; p < 0.05). The most frequent DOH was nail biting (58.7%). HG presented
      more depressive symptoms than HFG (p < 0.05). There was positive correlation
      between salivary cortisol levels and age (p < 0.01). Logistic regression analysis
      found association between symptoms of anxiety and the presence of DOH (OR = 2.35;
      p < 0.05). CONCLUSIONS: In conclusion, children and adolescents with DOH
      presented more symptoms of depression than their counterparts. Moreover, they
      were more likely to report symptoms of anxiety.

PMID- 25571682
TI  - Comparison of salivary calcium, phosphate and alkaline phosphatase levels in
      children with early childhood caries after administration of milk, cheese and GC
      tooth mousse: an in vivo study.
AB  - BACKGROUND AND OBJECTIVES: This study compares the Salivary Calcium, Phosphate
      and Alkaline Phosphataselevels in children with Early Childhood Caries after
      administration of Milk, Cheese and GC Tooth Mousse to a control group of caries
      resistant children. STUDY DESIGN: 90 kindergarten children both males and females
      aged 5 years, from the South Canara region were included in the study. Based on
      the dmfs score, children were divided into 3 groups: Control group, ECC group and
      S-ECC group. The Salivary Calcium, Phosphate and Alkaline Phosphatase levels in
      the sample were assessed before and after administration of Milk, Cheese and GC
      Tooth Mousse at three different intervals, i.e within 5 minutes, 30 minutes and
      60 minutes by using Spectrophotometry. RESULTS: The mean Salivary Calcium levels
      were higher in caries free group whereas Phosphate and Alkaline Phosphatase were
      lower in the caries free group which was statistically highly significant (p <
      0.001). The Tooth Mousse group showed higher bioavailability of calcium and
      phosphate which was statistically highly significant (p < 0.001). Salivary
      Calcium and Phosphate levels within 5 minutes after application of Milk, Cheese
      and Tooth Mousse were higher than at 30 and 60 minutes. Salivary Alkaline
      Phosphatase levels were lower than the baseline values at all the 3 intervals
      after administration of Milk, Cheese and Tooth Mousse and was statistically not
      significant (p > 0.05). CONCLUSION: Saliva should be saturated with Calcium and
      Phosphate to affect their bioavailability in amounts adequate for
      remineralizaton. Milk, Cheese and GC Tooth Mousse applicaton were equally
      beneficial in saturating the saliva with adequate amount of Calcium and
      Phosphate.

PMID- 25571683
TI  - Pre-eruptive intra-coronal resorption: controversies and treatment options.
AB  - Pre-eruptive intra-coronal resorption (PIER) is a defect located in the dentin of
      an unerupted tooth, just beneath the dentin-enamel junction, with a prevalence of
      0.5-2% of the teeth. The depth of the lesion is variable and may also reach the
      pulp. In the past, these lesions were confused with caries, and were therefore
      called "hidden" or "pre-eruptive caries". These defects are usually detected
      incidentally in routine dental radiographs. It has been proven that in the pre
      eruptive stage the lesions contain soft tissue and inflammatory cells. The
      present report describes the clinical management of a case of PEIR on a
      mandibular first permanent molar and discusses the alternatives for treatment.

PMID- 25571684
TI  - Effect of Bifidobacterium bifidum containing yoghurt on dental plaque bacteria in
      children.
AB  - OBJECTIVE: The aim of the present study is to determine the possible effect of
      Bifidobacterium bifidum DN-173 010 on dental plaque of children. STUDY DESIGN: 52
      children (25 F and 27 M), between the ages of 8-10, participated in the present
      study. The study had a double blind, randomized crossover design and the
      experimental period consisted of four consecutive time periods. During periods 2
      and 4 (2 weeks each), children consumed 110 g probiotic fruit yogurt
      (Bifidobacterium DN-173 010 (1 x 10(10) cfu/g)), or a placebo fruit yogurt per
      day. Available supragingival plaque (24 h later) was collected from teeth 16, 11,
      36 and 31 at baseline and at the end of periods 2 and 4. The counts of dental
      plaque mutans streptococci (MS) were evaluated using Dentocult SM (Strep Mutans).
      RESULTS: Changes of pre- and post-treatment levels of dental plaque MS were
      recorded for four consecutive sampling sites. There were no statistically
      differences between transition scores of test and placebo groups regarding
      different dental plaque sampling sites (p > 0.05) (unpaired t-test). CONCLUSION:
      Within the limitations of the present study, Bifidobacterium bifidum DN-173 010
      has no effect on dental plaque MS levels in children.

PMID- 25571685
TI  - Primate pulpal healing after exposure and TheraCal application.
AB  - AIM: The purpose of this in vivo study was to compare the effectiveness of a new
      light cured resin based dicalcium/tricalcium silicate pulp capping material
      (TheraCalLC, Bisco), pure Portland cement, resin based calcium hydroxide or glass
      ionomer in the healing of bacterially contaminated primate pulps. STUDY DESIGN:
      The experiment required four primates each having 12 teeth prepared with buccal
      penetrations into the pulpal tissues with an exposure of approximately 1.0 mm.
      The exposed pulps of the primate teeth were covered with cotton pellets soaked in
      a bacterial mixture consisting of microorganisms normally found in human pulpal
      abscesses. After removal of the pellet, hemostasis was obtained and the pulp
      capping agents applied. The light cured resin based pulp capping material
      (TheraCal LC) was applied to the pulpal tissue of twelve teeth with a needle tip
      syringe and light cured for 15 seconds. Pure Portland cement mixed with a 2%
      Chlorhexidine solution was placed on the exposed pulpal tissues of another twelve
      teeth. Twelve additional teeth had a base of GIC applied (Triage, Fuji VII GC
      America) and another twelve had a pulp cap with VLC DYCAL (Dentsply), a light
      cured calcium hydroxide resin based material. The pulp capping bases were then
      covered with a RMGI (Fuji II LC GC America). The tissue samples were collected at
      4 weeks. The samples were deminerilized, sectioned, stained and histologically
      graded. RESULTS: There were no statistically significant differences between the
      groups in regard to pulpal inflammation (H = 0.679, P = 1.00). However, both the
      Portland cement and light cured TheraCal LC groups had significantly more
      frequent hard tissue bridge formation at 28 days than the GIC and VLC Dycal
      groups (H = 11.989, P = 0.009). The measured thickness of the hard tissue bridges
      with the pure Portland and light cured TheraCal LC groups were statistically
      greater than that of the other two groups (H = 15.849, P = 0.002). In addition,
      the occurrence of pulpal necrosis was greater with the GIC group than the others.
      Four premolars, one each treated according to the protocols were analyzed with a
      microCT machine. The premolar treated with the light cured TheraCal LC
      demonstrated a complete hard tissue bridge. The premolar treated with the GIC did
      not show a complete hard tissue bridge while the premolar treated with VLC Dycal
      had an incomplete bridge. The pure Portland with Chlorhexidine mixture created
      extensive hard tissue bridging. CONCLUSION: TheraCal LC applied to primate pulps
      created dentin bridges and mild inflammation acceptable for pulp capping.

PMID- 25571686
TI  - Dental fluorosis: concentration of fluoride in drinking water and consumption of
      bottled beverages in school children.
AB  - OBJECTIVE: The purpose of the study was to identify dental fluorosis prevalence
      and to analyze its association with tap water fluoride concentration and beverage
      consumption in school children from the city of Oaxaca, who were receiving
      fluoridated salt. STUDY DESIGN: A cross-sectional study was performed on
      elementary public school children. Dean's Index was applied to assess dental
      fluorosis. The parents of the children who were studied completed a questionnaire
      about socio-demographic characteristics and type of beverages consumed by their
      children. A total of 917 school children participated in this study. RESULTS:
      Dental fluorosis prevalence was 80.8%. The most frequent fluorosis category was
      very mild (41.0%), and 16.4% of the children were in the mild category. The mean
      water fluoride concentration was 0.43 ppm (+/-0.12). No association was detected
      between tap water fluoride concentration and fluorosis severity. The multinomial
      regression model showed an association among the mild fluorosis category and age
      (OR = 1.25, [95% CI 1.04, 1.50]) and better socio-economic status (OR = 1.78,
      [95% CI 1.21, 2.60]), controlling for fluoride concentration in water. Moderate
      and severe fluorosis were associated with soft drink consumption (OR = 2.26, [95%
      IC 1.01, 5.09]), controlling for age, socio-economic status, and water fluoride
      concentration. CONCLUSIONS: The prevalence of fluorosis was high. Mild fluorosis
      was associated with higher socio-economic status, while higher fluorosis severity
      was associated with soft drink consumption.

PMID- 25571687
TI  - Serum-containing medium effect on isolation rate of dental pulp cells from
      cryopreserved intact deciduous teeth.
AB  - OBJECTIVES: To isolate cells from pulp of intact cryopreserved deciduous teeth.
      The null hypothesis raised here is to find no difference in the establishment of
      cell culture after cryopreservation (1) using culture medium supplemented with
      different concentrations of fetal bovine serum (FBS); and (2) between teeth with
      different stages of physiological root resorption. STUDY DESIGN: Intact deciduous
      teeth with different root resorption stages were cryopreserved using FBS and
      Dimethyl Sulfoxide (DMSO) medium (9:1) in a progressive freezing process, by
      placing the samples in the refrigerator (4 degrees C/60 min) and subsequently
      transferring them to a -80 degrees C freezer (controlled device -1 degrees
      C/min/24 hours), and finally into liquid nitrogen (-196 degrees C/30 days). After
      the thawing process, the cell isolation was performed by enzymatic digestion
      (type I collagenase). The cells were re-suspended into the culture medium with
      10% (G1) or 20% (G2) of FBS. Microscopic analysis was performed after 30 days to
      visualize the cell attachment. RESULTS: The culture establishment rate was higher
      in G2 (75%) than G1 (12.5%) (p = 0.041). There was no difference between the
      different stages of root resorption. CONCLUSIONS: It was possible to establish
      cell cultures from the pulp of intact cryopreserved deciduous teeth. The use of
      20% FBS after thawing improved the culture rate.

PMID- 25571688
TI  - In vitro and clinical outcome of sandwich restorations with a bulk-fill flowable
      composite liner for pulpotomized primary teeth.
AB  - OBJECTIVE: The present study determined whether primary molar pulpotomies showed
      equal in vitro and clinical success when restored with sandwich restoration with
      a bulk-fill flowable composite (BFRBC) liner versus a stainless steel crown (SSC)
      restoration. STUDY DESIGN: Sixty extracted human primary second molars with
      proximo-occlusal cavities were selected for in vitro test. The specimens were
      randomly divided into three groups (n = 20) and restored with sandwich
      restoration with a BFRBC liner composite (RBC) restoration and SSC. In addition,
      sixty teeth were selected from 20 children and each child had at least three
      primary molars (first and/or second primary molar) requiring pulpotomy. The
      patients were recalled for clinical and radiographic evaluation at approximately
      6- and 12-month intervals. RESULTS: The SSC restoration had significantly higher
      microleakage than the others. Although there was a significant difference between
      the RBC and the SSC (P = 0.02), the differences between the BFRBC and the RBC, as
      well as between the BFRBC and the SSC, were not statistically significant at the
      12-month radiographic evaluation (P = 0.33 and P = 0.11, respectively).
      CONCLUSION: In laboratory conditions, sandwich restoration with BFRBC liner
      showed a superior seal margins of pulpotomized primary molars. Based clinical and
      radiographical evaluation, teeth treated with formocresol pulpotomy and restored
      with sandwich restoration with BFRBC liner were as successful as those restored
      with a SSC.

PMID- 25571689
TI  - Green pigmentation in human teeth. A stereomicroscopic study.
AB  - Green pigmentation in teeth is an uncommon condition associated with bilirubin
      deposits in hard dental tissues. Its occurrence can cause anxiety to both the
      child and parents and is not diagnosed easily by clinicians. The aim of this
      study is to analyze the current knowledge about the etiology, the intraoral
      alterations, and the macroscopic and microscopic features of green teeth
      pigmentation related to a high bilirubin levels. A primary tooth was extracted
      and manually sliced into 600 microns thin sections. The slenderized slices were
      examined with a light microscope AxioImager M1 to evaluate the microscopic teeth
      structure. The clinical characteristics of teeth may help in the diagnosis of
      current or past systemic diseases. Pediatricians should be able to quickly note
      the signs in order to perform the proper diagnosis. This study may help
      clinicians gain more knowledge about the current status of this uncommon
      pathology.

PMID- 25571690
TI  - Multiple teeth fractures in dentinogenesis imperfecta: a case report.
AB  - Dentinogenesis imperfecta (DGI) is a hereditary defect consisting of opalescent
      teeth composed of irregularly formed and hypomineralized dentin. This paper
      presents the multiple fractures of DGI-affected teeth and suggests the reason of
      low fracture resistance by observing the dentin microstructures directly using
      scanning electron microscope (SEM) and by measuring its surface hardness using
      the Vickers hardness test. SEM revealed that while the enamel microstructure was
      similar in the DGI-affected and normal teeth, the microstructure of the DGI
      affected dentin was poorly woven and more loosely packed than that of the normal
      dentin. The Vickers hardness of the DGI-affected dentin was 4.89 times softer
      than the normal dentin. The low fracture resistance of DGI-affected teeth can be
      attributed to the poorly woven microstructure of their dentin, which leads to a
      reduction in hardness.

PMID- 25571691
TI  - Bispectral Index Monitoring: validity and utility in pediatric dentistry.
AB  - Reliable and safe provision of sedation and general anesthesia is dependent on
      continuous vigilance of patient's sedation depth. Failure to do so may result in
      unintended oversedation or undersedation. It is a common practice to observe
      sedation depth by applying subjective sedation scales and in case of general
      anesthesia, practitioner is dependent on vital sign assessment. The Bispectral
      Index System (BIS) is a recently introduced objective, quantitative, easy to use,
      and free from observer bias, and clinically useful tool to assess sedation depth
      and it precludes the need to stimulate the patient to assess his sedation level.
      The present article is an attempt to orient the readers towards utility and
      validity of BIS for sedation and general anesthesia in pediatric dentistry. In
      this article, we attempt to make the readers understand the principle of BIS, its
      variation across sedation continuum, its validity across different age groups and
      for a variety of sedative drugs.

PMID- 25571692
TI  - Timing of Class III treatment with unfavorable growth pattern.
AB  - When treating youngpatients with Class III malocclusion, factors such as timing
      and an accurate prediction of growth of the mandible are very important. Even
      though early interceptive treatment of Class III might often be successful,
      clinicians should be careful to not initiate early treatment with premolar
      extractions which will compromise the success of orthognathic surgery later due
      to mandibular prognathism. This case report presents an adolescent female patient
      who developed a severe Class III skeletal discrepancy during growth and was
      treated with surgery after her growth had finished.

PMID- 25571693
TI  - Electromyographic muscular activity improvement in Class II patients treated with
      the pre-orthodontic trainer.
AB  - OBJECTIVE: A study was designed to determine changes in the amplitude of the EMG
      muscular activity of the Masseter and Temporalis muscles at clench in children
      with a Class II, division 1 malocclusion treated with the pre-orthodontic Trainer
      functional appliance, for 12 months. STUDY DESIGN: 36 Class II, division 1
      malocclusion patients (mean age 7.6 +/- 1.3 years) composed the treated group and
      wore the functional appliance; 22 children with a similar age and malocclusion
      composed the untreated controls; and, 20 children with no dental malocclusion
      participated as normal controls. Electromyographic (EMG) muscular activity of the
      Temporalis and Masseter muscles were recorded before and after treatment.
      RESULTS: Subjects in the treated group reported a bilateral significant increase
      in the muscular electrical activity in the both tested muscles (p < 0.001). After
      treatment, they recorded values similar to those measured in normal controls,
      whereas the untreated controls remained on lower values. CONCLUSION: These
      results confirm that treatment with the pre-orthodontic Trainer functional
      appliance significantly increases the EMG muscular activity in the Temporalis and
      Masseter muscles at clench in patients with Class II, division 1 malocclusion.

PMID- 25571694
TI  - Fair pay for midwives!

PMID- 25571695
TI  - Public 'right behind' midwives over pay and industrial action.

PMID- 25571696
TI  - NMC fee rise ill-timed and ill-judged say midwives.

PMID- 25571697
TI  - New international standards provide reliable measures of fetal growth.

PMID- 25571698
TI  - Nutrition in pregnancy: keeping in mind the priorities.
AB  - Since brain development is explosive during the second half of human fetal life,
      the concept of 'brain selective nutrients' is a necessary point of departure to
      identify the basic nutritional needs of pregnant women. Two important brain
      selective nutrients are considered: iodine, essential in thyroid hormone
      production, and DHA, a very long chain polyunsaturated acid of the omega 3
      family. Both of them are abundant in the seafood chain only. The particular case
      of pregnant women who do not have access to the seafood chain is considered. The
      focus is on the need to avoid blocking agents of the metabolic pathways of
      unsaturated fatty acids, particularly pure sugar, alcoholic beverages and trans
      fatty acids.

PMID- 25571699
TI  - Digestive health in pregnancy.
AB  - Women experience the physiological changes of pregnancy in a variety of ways.
      Changes in pregnancy are associated with changing hormone levels. These hormonal
      changes have an impact on all body systems. Midwives need to have an
      understanding of the changes so that they can enable women to manage their
      digestive health effectively. The midwife needs to be vigilant in history taking
      to understand the woman's experiences and to be able to offer appropriate support
      and advice. There are a number of conventional and alternative treatments that
      can help to prevent and alleviate symptoms. This article will consider the impact
      on the gastro-intestinal system and how changes can be managed.

PMID- 25571700
TI  - Magnesium: the relevance of research.
AB  - The recent flurry of apparently conflicting research findings is likely to have
      left practitioners, if not at a loss, at least bemused about this topic. How best
      should the midwife advise the childbearing woman on the subject of magnesium
      supplementation during pregnancy? It is possible that the recent welter of words
      may not have been of very much help to any of those who read them. In this paper
      I suggest that the researchers may actually be missing the point as far as
      providing useful and usable data is concerned.

PMID- 25571701
TI  - Perspectives on tongue-tie.
AB  - In light of the recent NCT petition to Health Minister Dr Dan Poulter MP to
      update guidelines for the diagnosis and treatment of tongue-tied babies to avoid
      stress and difficulties feeding for babies and their families, discussion has
      been sparked amongst mothers, midwives, health visitors and breastfeeding
      counsellors as to how exactly services could be improved. Access to evidence
      based, family-centred care is vital to address this potentially distressing
      condition. But are we too quick to jump in with a diagnosis that may ultimately
      be of no clinical significance? This articles presents two professional
      perspectives on the issue and highlights the pertinent research available.

PMID- 25571702
TI  - Brilliant breastfeeding!
AB  - The 9th lactation and breastfeeding symposium was hosted in Madrid, Spain in
      April 2014. This year the team also shared the information further afield, taking
      to Twitter to run live chats. This article reports on three discussions of
      interest to The Practising Midwife readers: what is regarded as 'normal' in terms
      of breastfeeding; human milk lipids and health outcomes; and considering the
      research into the lactating mammary gland.

PMID- 25571703
TI  - To ECV or not to ECV? The current evidence base concerning external cephalic
      version.
AB  - External cephalic version (ECV) is the technique of attempting to turn a baby in
      the womb from a head-up to a head-down position. The practice is grounded on
      evidence that vaginal breech birth (VBB) presents greater short-term risks for
      babies than caesarean section (CS) (Hofmeyr et al 2011), but that labour and
      vaginal birth also offer benefits to both mothers and babies. Therefore, if we
      can turn babies to a head-down position, we can reduce the risks associated with
      both VBB and CS, and enable mother and baby to benefit from labour and birth.

PMID- 25571704
TI  - Midwifery basics mentorship: The role and responsibilities of a midwifery mentor.

PMID- 25571705
TI  - Are emergency mnemonics help(err)ful?

PMID- 25571706
TI  - Reflections from Prague.

PMID- 25571707
TI  - Post caesarean section wound care.

PMID- 25571708
TI  - [The effects of equol on enzymes related to testosterone synthesis and vimentin
      in the testis of perinatal mice by organ culture in vitro].
AB  - OBJECTIVE: To investigate the effects of Equol on genes and protein expression of
      testosterone synthesis related enzymes and Vimentin in testis of perinatal mice
      in vitro. METHODS: Testes were isolated and cultured in infiltrating type
      rotating device for 72 h. The testes were randomly divided into five groups and
      treated with Equol (DMSO control, 0.01, 0.10, 1.00, 10.00 MUmol/L Equol).
      Morphological changes were observed by HE staining under optical microscope.
      Expressions of 3beta-hydroxysteroid dehydrogenase (3beta-HSD),P450 side-chain
      cleavage enzyme (P450scc), Vimentin were detected by real-time PCR and
      immunohistochemistry. RESULTS: No apparent morphological change in testes was
      observed compared to control group. The mRNA expression of 3beta HSD, P450Scc,
      Vimentin show no statistical significance(P> 0. 05) in all Equol group, while the
      protein expressions of 3beta-HSD, Vimentin, P450scc increased in 0. 10 MUmol/L
      and decreased in 10.00 MUmol/L Equol group. CONCLUSION: Equol exposure can affect
      3beta-HSD, P450Scc, Vimentin expression in testes in vitro, means Equol may have
      potential adverse effects on testosterone production and spermatogenesis.

PMID- 25571709
TI  - [Inhibition of HCN1 channels by ketamine accounts for its antidepressant
      actions].
AB  - OBJECTIVE: To investigate the roles of hyperolarization-actived cyclic nucleotide
      gated channels 1 (HCN1) in antidepressant actions of ketamine (KET). METHODS:
      Male HCN1 knock out (HCN1-/- ) and wildtype (HCN1+/+ ) C57BL6 mice (8-12 weeks,
      20-25 g) were chosen. The depression model of mice was developed by continuously
      oral administration of low dosage of corticosterone (CORT). The immobility time
      in forced swimming tests (FST) was used to assess the depressive state of mice.
      Then the two genotype depressive mice were treated with single intraperitoneal
      injection of 5 mg/kg ketamine (KET group, n=7) or same volume of normal saline
      (NS group, n=7) respectively. After treatment, the immobility time at 30 min, 24
      h and 7 d after the intraperitoneal injection of ketamine or normal saline in
      CORT-treated mice were compared. In addition, normal HCN1-/- and HCN1+/+ mice
      were intraperitoneally injected of BrdU and then treated with 5 mg/kg ketamine
      (KET group, n=5) or same volume of normal saline (NS group, n= 5) by single
      intraperitoneal injection. Each group was euthanized for immunohistochemical
      processing of 5-Bromo-2-deoxyuridine (BrdU)-labeled cells in hippocampus at 24 h
      after the intraperitoneal injection of saline or ketamine. RESULTS: The
      immobility time in FST of HCN1-/- mice was less than the HCN1+/+ mice before
      administration of CORT. It shows that the depressive state of HCN1-/- mice is
      less intensive than that of HCN1+/+ mice. And the immoblility time in both HCN1-/
      and HCN1+/+ mice was increased after oral administration of low dose
      corticosterone, with an increase in depression. In addition, the comparisons were
      also made to the reduction of immobility time within 30 min, 24 h and 7 d. At any
      time point, the reduction of immobility time in HCN1+/+ KET group was higher than
      those in the other three groups (P<0. 05). Furthermore, there were no statistical
      significances among the three groups including HCN1-/- KET group, HCN1+/+ NS
      group, HCN1-/- NS group at any point. The number of newborn neurons were more in
      HCN1 mice than HCN1+/+ mice after the treatment of normal saline. Compared with
      the NS group, the number of neonatal neurons labeled by BrdU were increased after
      the intraperitoneal injection of ketamine in HCN1+/+ mice but not in HCN1-/-
      mice. CONCLUSION: Inhibition of HCN1 channels by ketamine accounts for its
      antidepressant actions.

PMID- 25571710
TI  - [Reversal effect and its mechanism of (- )-5-N-acetylardeemin on adriamycin
      resistance in multidrug-resistant cancer cells A549/Adr and MCF-7/Adr].
AB  - OBJECTIVE: To explore the reversal effect of (- )-5-N-acetylardeemin on
      adriamycin resistance in multidrug-resistant cancer cells including human breast
      cancer cells MCF-7/Adr and human non-small cell lung cancer cells A549/Adr in
      vitro. METHODS: The multidrug-resistant cancer cells MCF-7/Adr, A549/Adr and
      their respective parental cells were treated with different concentrations of (-
      )-5-N-acetylardeemin and adriamycin individually or in combination. Cell death
      was detected based on the release of lactate dehydrogenase (LDH) using a
      cytotoxicity detection kit. Intracellular accumulation of adriamycin was measured
      by the detection of fluorescence intensity of cell lysates using microplate
      reader. The expression of P-glycoprotein (P-gp) was evaluated by Western blot.
      RESULTS: (-)-5-N-acetylardeemin significantly reversed the adriamycin resistance
      in MCF-7/Adr and A549/ Adr in a dose-dependent manner, and the reversal folds
      were 10. 8 in MCF-7/Adr cells and 20.1 in A549/Adr cells with the treatment of 10
      MUmol/L (-)-5-N acetylardeemin. (- )-5-N-acetylardeemin also enhanced the
      sensitivity of parental MCF-7 and A549 cells to adriamycin. The fluorescence
      intensity in both MCF-7/Adr and A549/Adr cells, which reflected the intracellular
      accumulation of adriamycin, were significantly enhanced by ( -)5-N-
      acetylardeemin in a dose-dependent manner. The expressions of P-gp in MCF-7/Adr
      and A549/Adr cells were significantly inhibited by (- )-5-N-acetylardeemin.
      CONCLUSION: (- )5-N-acetylardeemin could reverse the multidrug resistance in
      cancer cells through inhibiting the expression of P-gp and enhancing the
      intracellular accumulation of cytotoxic drug.

PMID- 25571711
TI  - [Bone mesenchymal stem cell transplantation for acute myocardial infarction: in
      vivo tracing with multi-modality molecular imaging].
AB  - OBJECTIVE: To investigate the feasibility of tracking bone mesenchymal stem cell
      (BMSCs) dual- labeled with polyethylenimine 2k-superparamagnetic iron oxide
      (PEI2k-SPIO) and Luciferase transplantation for acute myocardial infarction in
      vivo by using magnetic resonance imaging (MRI) and fluorescence imaging. METHODS:
      BMSCs/Luciferase was incubated with culture medium containing PEI2k-SPIO for 24
      h. Prussian-blue staining and MTT were used to assess the efficacy and safety of
      labeling with PEI2k-SPIO. Guided with echocardiography, the dual-labeled BMSCs
      were injected into the margin of infarction myocardium. MRI and fluorescence
      imaging were performed to monitor the cells in vivo at different times (1,2,3,7
      d). RESULTS: As demonstrated by MTT, there was no significant difference in
      survival rate between the labeled and unlabeled cells (P>0. 05). Within a week
      after transplantation, all PEI2k-SPIO-labeled BMSCs showed a significant
      decreased signal on MRI. Dual-labeled BMSCs were detected bioluminescence with
      fluorescence imaging, but disappeared after one week. CONCLUSION: Multi- modality
      imaging can not only trace the location of labeled BMSCs but also demonstrate the
      survival of labeled BMSCs in vivo.

PMID- 25571712
TI  - [Anti-leukemia effect of oridonin on T-cell acute lymphoblastic leukemia].
AB  - OBJECTIVE: To investigate the antileukemia effect of oridonin on T-cell acute
      lymphoblastic leukemia cell line CEM. METHODS: Human T-cell acute lymphoblastic
      leukemia cell line CEM was cultured in vitro. The 50% inhibition concentration
      (IC50) of oridonin against CEM cells was examined using modified MTT assay. The
      cellular morphologic changes were observed using a light microscope. The percent
      of apoptosis of CEM cells after drug treatment was evaluated by flow cytometric
      analysis. The active levels of AKT/mTOR, RAF/MEK/ ERK, STAT5 signaling pathways
      and the expression levels of Bcl-2 and BAX were examined by Western blot.
      RESULTS: Oridonin inhibited the growth of CEM cells in time- and dose dependent
      manner and the ICs0 of oridonin was (7. 37+/- 1. 99) MUmol/L after 72 h
      treatment. The cellular membrane of CEM cells treated with oridonin became
      unsharp, some of them disintegrated. Oridonin induced apoptosis in CEM cells and
      the percent of apoptosis rate after 0, 5, 7.5, 10 MUmol/L oridonin treatment for
      24 h were (4. 8+/-2. 11)%, (19.03+/-12.54)% ,(40.27+/- 3.31) / and (57. 23 +/- 6.
      69)% respectively. Oridonin inhibited activation of mTOR, P70S6, 4EBP1, RAF. ERK
      and STAT5 signaling protein, which were constitutively activated in CEM cells,
      however, oridonin had no inhibitory effect on AKT kinase. Oridonin down-regulated
      the level of anti apoptotic protein Bcl-2 and up-regulated the expression of pro
      apoptotic protein Bax. CONCLUSION: Oridonin exerted antileukemia effect in CEM
      cells by inhibiting the activation of mTOR/P70/4EBP1, RAF/ERK and STATS signaling
      pathways, down-regulating the expression of Bel-2 and up-regulating the
      expression of BAX.

PMID- 25571713
TI  - [Smokeless tobacco extract affects biological properties of the pre-osteoblast
      cell line MC3T3-E1 ].
AB  - OBJECTIVE: To investigate the effects of smokeless tobacco extract (STE) on
      biological properties of osteoblast, and to identify possible pathological
      mechanisms of osseointegration. METHODS: MC3T3-E1 Sub-clone 14 cells were
      cultured in the presence of STE at 0 (control group),0. 01,0. 1,1,5,10 g/L. The
      cell proliferation was measured by MTT assay 1 d, 3 d, 5 d, and 7 d after
      exposure. The F-actin cytoskeleton of MC3T3 was stained with Rhodamine and DAPI,
      and then examined under a confocal laser scanning microscope 24 h after exposure
      to STE. The mRNA expressions of interleukin-6 (IL-6) and core-binding factor
      alphal(Cbfalphal) were quantified by real- time PCR (RT-qPCR) 48 h after exposure
      to STE. RESULTS: The MTT assay showed that 0. 01-10 g/L STE inhibited MC3T3
      proliferation (P<0. 05). Prolonged time enabled 5-10 g/L STE to inhibit MC3T3
      proliferation (P<0. 05). Network structure in F-actin cytoskeleton was
      demonstrated in the controls. In the cells exposed to STE, F-actin cytoskeleton
      started to change with disruptive structures. As the concentration of STE
      increased, the changes became more significant. STE increased the mRNA expression
      of IL-6 at the concentration of 5 g/L and 10 g/L (P<0.05), decreased the mRNA
      expression of Cbfalpha1 at the concentration of 0. 1-10 g/L (PO<0. 05).
      CONCLUSION: Tobacco may inhibit osteoblast proliferation, destroy F-actin
      cytoskeleton structure, increase the mRNA expression of IL-6 and decrease the
      mRNA expression of Cbfalpha1, and inhibit cell differentiation and adhesion
      accordingly. Smoking is a disadvantage to osseointegration.

PMID- 25571715
TI  - [Effect of electroacupuncture on the expression of oligodendrocyte precursor
      cells in rats with compressed spinal cord injury].
AB  - OBJECTIVE: To investigate the effect of electroacupuncture on the expression of
      oligodendrocyte precursor cells in rats with compressed spinal cord injury (CSCI)
      and to explore the mechanism of remyelinization. METHODS: Thirty-six SD rats were
      randomly divided into a control group and three treatment groups with 3 d, 7 d
      and 14 d of treatment respectively. Acupuncture was given to rats in the
      treatment groups through jiaji point, double zusanli (ST36), and double taixi
      (KI3). Electroacupuncture (continuous wave, 2 Hz/1. 5 V, 30 min) was applied for
      the double zusanli (ST36) and double taixi (KI3). Ethological alterations of the
      rats were observed with quantitative assessment of neurologic function. The
      ultrastructure changes of nerve fibers in white matter were determined under
      electronic microscope. Expressions of NG2 protein, an OPC marker, was observed by
      Western blot. RESULTS: No significant changes in neurologic function and G-ratio
      were observed after three days and seven days of electroacupuncture treatment
      (P>0. 05). However, 14 d of electroacupuncture treatment made a significant
      change compared to the 7 d treatment group and the control group (P<0. 05). The
      electronic microscope showed axons with varied degree of swollen, degenerated and
      lost cell organelle in axoplasm, edema in myelin sheaths, disordered, thickened
      and even broken layers of myelin sheaths in the rats with CSCI. The rats in the
      treatment groups had milder swollen axons and more compacted layers of myelin
      sheaths compared to their controls. Western blot showed that the expression of
      NG2 was increased with time and the differences among the three treatment groups
      were statistically significant (P<0. 05). The rats in the treatment groups also
      had higher expressions of NG2 than their controls at 7 d and 14 d (P<0. 05).
      CONCLUSION: Electroacupuncture can improve inflammation and edema in the injured
      nerve fibers and up regulate NG2 expression and remyelination of the injured
      nerve fibers in rats with CSCI.

PMID- 25571714
TI  - [Fluid shear stress and raloxifene stimulates the proliferation of osteoblast
      through regulating the expresstion of beta-catenin and estrogen receptor alpha].
AB  - OBJECTIVE: To investigate how the fluid shear stress and raloxifene alone or in
      combination affect the proliferation of murine pre-osteoblast MC3T3-E1. METHODS:
      MC3T3-E1 cells cultured in vitro were treated with the fluid shearing stress and
      raloxifene alone or in combination, and the MC3T3-E1 cells without treatment were
      set as control (O group), treated with estrogen receptor antagonist ICI-182780
      (10-7 mol/L, I group) were set as negative control group. The cells were observed
      underoptical inverted microscope from cell shape, size, and nuclear shape to
      quantity respectively before harvested. The levels of mRNA and protein of beta
      catenin and estrogen receptor alpha (ERalpha) were detected by reverse
      transcription polymerase chain reaction (RT-PCR) and Western blot respectively.
      RESULTS: (1) As compared with those of the control group and negative control
      group, the cell proliferation, the expression of ERalpha mRNA and protein, and
      protein expression of beta-catenin significantly increased in the groups of
      raloxifene, fluid shearing stress and raloxifene combination fluid shearing
      stress (P<0. 05). RT PCR analysis showed that the levels of beta-catenin mRNA
      though were not changed significantly in raloxifene group compared with O group
      (P>0.05), increased significantly in groups of fluid shear stress and raloxifene
      combination fluid shear stress. (2) The cells number, the expression of beta
      catenin and ERalpha were not changed significantly between raloxifene group and
      fluid shearing stress group (P> 0. 05), but all test parameters in groups of
      raloxifene combination fluid shearing stress were higher than that of the
      previous two groups (P<0. 05). CONCLUSION: Fluid shear stress and raloxifene, the
      selective estrogen receptor modulator, were verifed to be able to promote MC3T3
      E1 proliferation, increase the expression of beta-catenin and ERalpha, and the
      combination functioned synergicly significantly. Fluid shear stress and
      raloxifene may possiblely affect the osteoblast proliferation by regulating the
      signaling pathways of Wnt/beta-catenin and ER.

PMID- 25571716
TI  - [The effects of electro-acupuncture on the signaling pathway of TLR/MYD88 in
      ankle joint synovial tissue of acute gouty arthritis rats].
AB  - OBJECTIVE: To investigate the effects of electro-acupuncture ( EA) on the related
      protein expression of the signaling pathway of the toll-like receptor2
      (TLR2)/myeloid differentiation factor (MYD) 88 in ankle joint synovial tissue of
      acute gouty arthritis (AGA) rats. METHODS: Fifty male SD rats were randomly
      divided into 5 groups: normal group, SMD group, AGA model group, medication group
      and EA group, 10 rats in each group. SMD group established model by inducing SMD,
      other groups established AGA model by inducing monosodium urate, except the
      normal group. Two days before model was established, normal and SMD and AGA model
      groups were lavaged with normal saline (20 mL/kg), medication group was lavaged
      with colchicine solution (1 mg/kg), EA (1. 5-2 Hz, D.-D. wave, 9 V, 1-3 mA) was
      applied to"Sanyinjiao" (SP6),"Jiexi"(ST41) and "kunlun" (BL60) for 20 min, once
      daily, continuously for 9 days. Then the join sewlling index was observed
      periodically, the protein expression of TLR2 and MYD88 was determined by
      immunohistochemistry. RESULTS: Compared to the normal group, the join sewlling of
      the SMD group in test join increased significantly (P<0. 05) and the protein
      expression of TLR2 and MYD88 in synovial tissue has not statistically significant
      (P>0.05), the oin sewlling and protein expression of TLR2 and MYD88 in synovial
      tissue of model group increased significantly P<0. 05); The medication and EA
      group compared to the model group, the protein expression of TLR2 and MYD88 in
      synovial tissue decreased significantly (P <0. 05), the join sewlling in test
      join decreased significantly P<1. 05); There were not statistically significant
      between the EA group and the medication group (P>0.05). CONCLUSION: EA can
      alleviate the symptoms of AGA, which may be related to regulation of the protein
      expression Y TRI and MYD88 in the TLR/MYD88 signaling pathway.

PMID- 25571717
TI  - [The distribution of caspase-3 positive apoptotic cells in 18 months old SD rat's
      brainstem compared with that in 3 months rat].
AB  - OBJECTIVE: To study whether there is apoptosis in brainstem neurons while aging
      by oberving the distribution of Caspase-3 positive apoptotic cells in in
      brainstem of young and old SD rats. METHODS: Healthy male SD rats were divided
      into 2 groups (3 and 18 month-old respectively), 3 rats each group. Brainstem
      specimens were treated followed the brainstem's common paraffin embedding,
      sectioning and HE staining procedures (sections were 6 MUm in thickness). The
      sections were also determined by Caspase-3 immunostaining and TUNEL. The Caspase
      3 positive cells on the rat stereotaxic atlas were drew, then composed the
      sections into a 3D model. RESULTS: Compared to 3 month-old rats, there were more
      Caspase-3 positive neurons in the brainstem and the positive neurons were
      distributed more extensively in 18 month-old rats spectially in nucleus of
      solitary tract and pontine reticular nuclei. CONCLUSION: More neurons suffer
      apoptotic changes in the brainstem while aging.

PMID- 25571718
TI  - [Effects of vinegar on tooth bleaching and dental hard tissues in vitro].
AB  - OBJECTIVE: To determine the effects of three acidoid bleaching agents on tooth
      color and dental hard tissues. METHODS: Bovine tooth blocks with 5 mm x 3 mm
      enamel surface exposure were randomly divided into four groups: white vinegar
      group (group A),apple vinegar group (group B), 30% hydrogen peroxid group (group
      C) and deionized water (group D), each containing ninety blocks. In each group,
      the tooth blocks were further equally divided into three sub groups, exposing to
      their respective bleaching agents for 30 s, 1 min and 3 min, respectively. The
      experiment was performed under simulated oral environment. The changes in
      color,microhardness and morphological characteristics of the tooth blocks were
      tested by ShadeEye NCC,microhardness tester and SEM. RESULTS: Tooth blocks
      exposed to white vinegar had the most notable decrease in hardness, changes in
      color and morphological characteristics enamel surface. CONCLUSION: White
      vinegar, apple vinegar and hydrogen peroxidhave bleaching effects on teeth, but
      white vinegar may causehigher levels of damage to the hardness and surface
      configuration of teeth.

PMID- 25571719
TI  - [Effects of hyperoxia on the apoptosis of lung cells and notchl signaling
      pathways].
AB  - OBJECTIVE: To investigate the changes of lung cell apoptosis and the expression
      of notch signaling in the lung of neonatal rats exposed to hyperoxia and to
      explore the internal relationship between notch1 and hyperoxia-induced lung
      injury. METHODS: 120 neonatal Sprague-Dawley rats of 22-day gestational age were
      randomized continually exposed to hyperoxia (FiO2 = 95%, hyperoxia group) or room
      air (FiO2 21%, air group) 30 minutes after birth. The notch signaling expression
      in the lung were detected by immunohistochemical methods respectively at 4, 7, 14
      days after inhale hyperoxia or air. At the same time, pathological changes in the
      different groups were also observed with light microscope and lung cell apoptosis
      was determined quantitatively by terminal deoxynucleotidyl transferase-mediated
      dUTP nick-end labeling (TUNEL) methods. RESULTS: The biopsy test showed lung
      injury in hyperoxia group. The amount of apoptosis cell in hyperoxia was higer
      than that in the control group, and increased with the prolongation of hyperoxia
      supply. Positive staining for North1 in hyperoxia group was much lower than that
      in control group at every time point (P<0. 01, P<0. 05). CONCLUSION: Continually
      hyperoxic exposure might resulted in the lung injury and development of arrest.
      The abnormal expression of notch signaling might contributed to the pathogenesis
      of hyperoxia-induced lung injury in newborn rats.

PMID- 25571720
TI  - [Regulation of Thl/Th2 cells by T cell-mediated transcription factor in rats with
      chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To determine T box expressed in T cells (T bet), GATA binding protein
      3 (GATA 3), and retinoid-related orphan nuclear receptor gammat (RORgammat) in
      rats with chronic obstructive pulmonary disease (COPD). METHODS: Thirty rats were
      randomly divided into a control and a COPD group. The COPD model was established
      through smoking and lipopolysaccharide (LPS) tracheal instillation. Pulmonary
      function of the rats was measured 28 d after the establishment of the COPD model
      by a spirometer. Enzyme linked immunosorbent assay was performed to detect serum
      gamma interferon (IFN-gamma), interleukin (IL)-4, and IL-17. The expressions of T
      bet, GATA-3, and RORgammat protein in lung tissues were determined by Western
      blot. RESULTS: Compared with the controls, the COPD rats had decreased pulmonary
      function and expression of serum IL-4, and increased INF-gamma, IL- 17, Th1/Th2,
      T-bet, T bet /GATA-3, and RORgammat protein (P<0. 05). Forced expiratory volume
      in 0. 3 seconds (FEV 0.3) was negatively correlated with INF gamma and T-bet/GATA
      3. Forced vital capacity (FVC) was positively correlated with IL 4. FEV0.3/FVC
      was negatively correlated with Thl/Th2, T-bet and T-bet/GATA-3. Peak expiratory
      flow (PEF) was negatively correlated with IL-17, T bet, and RORgammat (P<0. 05).
      Thl/Th2 was positively correlated with T bet/GATA-3. IL-17 was positively
      correlated with RORgammat. T bet/GATA-3 was positively correlated with RORgammat
      (P<0. 05). CONCLUSION: Imbalanced regulation of T bet / GATA 3 and RORgammat on
      Th1/Th2 and Th17 cells is associated with the occurrence of COPD.

PMID- 25571721
TI  - [The role of Treg/Thl7 and calprotectin in ulcerative colitis rat model].
AB  - OBJECTIVE: To investigate the roles of helper T cells (Th), regulatory T cells
      (Treg) and calprotectin in the pathogenesis of ulcerative colitis (UC) in the rat
      model. METHODS: Thirty rats were randomly divided into normal control (NC) group
      and UC model (UC) group. The rats of UC group were replicated using the mixed
      solution of 2, 4,6 trinitrobenzene sulfonic acid (TNBS) / ethanol through the
      intestinal tract. The rats of NC group were given NaCI solution enema. Three
      weeks after UC modeling, the morphology changes of colon tissue were observed.
      The serum levels interleukin (IL)-1beta, IL-10, IL-17, IL-23 and calprotectin
      (CP) were detected by enzyme-linked immunosorbent assay. The changes of Treg in
      peripheral blood were measured by flow cytometry. The expressions of IL-17, CP,
      and transcriptional regulatory proteins of decision Treg cell differentiation and
      function (FoxP3) in colon tissue were detected by Western blot and
      immunohistochemistry. RESULTS: UC group was observed with obvious colon tissue
      injury and inflammatory cells infiltration in intestinal tissue, compared with NC
      group, the expression of IL-1beta,IL-17,IL-23,CP in serum were increased, while
      the expression of IL-10, the number of Treg were decreased in UC group (P<0. 05
      or P(<0. 01). Compared with NC group, the expression of IL-17, CP in colon tissue
      were significantly increased in UC group (P(<0.05), and the expression of FoxP3
      was increased (P(0. 05). CONCLUSION: Expressions of calprotectin, IL-17 of
      intestinal tissue, serum are increased in rat of ulcerative colitis, which to
      lead to the imbalance of Treg/Thl7 cells, and elevate inflammatory responses.
      These factors have promote the occurrence and development of ulcerative colitis.

PMID- 25571722
TI  - [Effect of human concentration nucleoside transporters 1 and multi-drug
      resistance protein 4 gene polymorphism on response of chronic hepatitis B to
      nucleoside analogues treatment].
AB  - OBJECTIVE: To investigate the effect of human concentration nucleoside
      transporters 1 (hCNT1/ SLC28A1) and multi-drug resistance protein 4 (MRP4/ABCC4)
      gene polymorphism on the response of chronic hepatitis B patients to nucleoside
      analogues treatment. METHODS: There were 136 patients of chronic hepatitis B
      treated with entecavir (68) or telbivudine (68). The allele and gene frequency
      distributing of the four loci of hCNT1/SLC28A1 and MRP4/ABCC4 as well as the
      polymorphisms were detected in all patients by multiplex snapshot single base
      extension method. Based on the treatment response, the patients were divided into
      primary partial response (PPR) group and complete viral response (CVR) group,
      hCNTI/SLC28A1 and MRP4/ABCC4 gene polymorphism between these two groups were
      analyzed. RESULTS: The rates of PPR and CVR were 56. 6%00 (77 136) and 43. 4%
      (59/136) respectively. There was no statistical difference in baseline HBV DNA
      value, hepatitis B virus genotype and HBeAg status between PPR and CVR groups
      (P=0.148, P= 0. 622,P=0. 071) . The distribution of allelotype rs2290272 C/T and
      rs11568658 G/G in PPR group were higher than those in CVR group (P=0.043.
      P=0.049). Haplotype of C/A/T/C and C/C/G/G in CVR group were higher than those in
      PPR group (P=0. 024,P=0. 005). CONCLUSION: The single nucleotide polymorphisms
      (SNPs) of two candidate genes, including rs2290272 C/T of hCNT1/SLC28A1 and
      rs11568658 G/G of MRP4/ABCC4, may weak the response of chronic hepatitis B to
      nucleoside analogues treatment, as well as haplotype of C/A/T/C and C/C/G/G may
      enhance the response.

PMID- 25571723
TI  - [Insertion/deletion polymorphism of IL1A 3'-UTR associated with the
      susceptibility of prostate cancer ].
AB  - OBJECTIVE: To identify the association between the insertion/deletion
      polymorphism of interleukin- 1A gene (IL1A) and the susceptibility of prostate
      cancer (PCA). METHODS: We performed a case-control study enrolling 131 PCA
      patients and 229 healthy control subjects in a Chinese Han population. The TTCA
      insertion/ deletion polymorphism (rs3783553) in 3'-UTR of IL1A gene was genotyped
      by PCR-RFLP method. RESULTS: The genotype distribution of rs3783553 in both
      groups met the requirements of Hardy-Weinberg equilibrium. Significantly reduced
      PCA risk was associated with D/I and I/I genotype compared to D/D genotype (P<0.
      001, OR=O. 48, 95%CI: 0.31-0.74), and allele I is associated with the reduced PCA
      risk (P=0. 001,OR=0. 56,95% CI: 0. 40-0. 79). CONCLUSION: TTCA insertion allele
      of rs3783553 contributes to the reduction of the susceptibility to prostate
      cancer.

PMID- 25571724
TI  - [The expression of EMT associated protein CK-18 and vimentin in gestational
      trophoblastic disease ].
AB  - OBJECTIVE: To analyze the expression and clinicopathologic features of epithelial
      to mesenchymal transition (EMT) associated protein of cytokeratin-18 (CK-18) and
      vimentin in gestational trophoblastic disease (GTD). METHODS:
      Immunohistochemistry was used to determine theexpression of CK-18 and vimentin in
      normal pregnancy villis (39 cases), hydatidiform mole (HM) (33 cases) and
      gestational trophoblastic neoplasia (GTN) (invasive mole 27 cases and
      choriocarcinoma 5 cases). RESULTS: The GTN group had significantly lower levels
      of CK-18 compared with the normal pregnancy villis group and the HM group (P<0.
      01). Vimentin was weakly positive in all kinds of trophocyte. There was no
      significance among normal pregnancy villis, HM and GTN groups (P> 0. 05). In HM,
      expression level of CK18 was significantly lower with the increase of the
      pathological malignancy (P<0. 01). And in GTN, the expression of CK-18 was
      significantly lower with the increase of the tumor anatomy stage (P<0. 001).
      CONCLUSION: The expression of CK-18 decreases with the increase of tropohblast
      malignancy, which indicates that CK-18 may be involved in malignant
      transformation of trophocytes and EMT may play an important role in the malignant
      transformation of GTN.

PMID- 25571725
TI  - [Preliminary study of contrast-enhanced ultrasonography in the evaluation of
      angiogenesis in ovarian tumors].
AB  - OBJECTIVE: To investigate the role of contrast-enhanced ultrasonography (CEUS)
      with pulsed inversion harmonic imaging in the evaluation of angiogenesis in
      ovarian tumors. METHODS: Forty-two patients of ovarian tumor received CEUS
      examination, in which the rise time (RT), peak intensity (PI), area under the
      curve (AUC), time from peak to one half (TTH) and time to peak (TTP) of ovarian
      tumors were measured. The post- surgical specimens of ovarian tumors were
      analysed by the stain with polyclonal antibodies against vascular endothelial
      growth factor (VEGF) and CD34. Correlations between the index of VEGF,
      microvessel density (MVD) and ultrasonic perfusion parameters were studied.
      RESULTS: MVD and VEGF index of ovarian tumors were significantly correlated with
      CEUS perfusion parameters including PI, AUC and TTH. The correlation coefficients
      of MVD with PI, AUC and TTH were 0. 569, 0. 623 and 0. 585 respectively; and the
      correlation coefficients of VEGF with PI, AUG and TTH were 0. 516,0. 640 and 0.
      591 respectively. There were significant differences of the perfusion parameters
      between high and low MVD group. CONCLUSION: The perfusion parameters PI, AUC and
      TTH in CEUS were correlated with MVD and VEGF in ovarian tumors, which may be
      useful in the evaluation of tumors angiogenesis.

PMID- 25571726
TI  - [Personality traits of Chinese adolescents with non-suicidal self injury and
      suicide attempt ].
AB  - OBJECTIVE: To examine the personality traits of Chinese adolescents with non
      suicidal self-injury (NSSI) and suicide attempt (SA). METHODS: A cross-sectional
      survey on 2 131 middle school students in Dujiangyan city was conducted using the
      Eysenck Personality Questionnaire (EPQ, Children's Version) and Self- harm
      Behaviors Questionnaire (SHQ). The sample was stratified selected, comprising 1
      085 boys and 1 046 girls with an average age of (13. 92+/-1. 63) years. The study
      population was categorized into four groups according to their non-suicidal and
      suicidal behaviors measured by the SHQ: those without self-harm (NoSH), those
      with non suicidal self-injury exclusively (NSSI only), those only with suicide
      attempts (SA only) and those with both NSSI and SA (NSSI+ SA). A MANCOVA model
      was constructed, with age and gender treated as covariates. We compared the four
      subscales of EPQ (Neuroticism, Psychoticism, Extraversion, Lie) between the four
      groups of study populations. RESULTS: NSSI was reported by 23. 2% (n 494) of
      respondents, and 3. 2% (n= 68) reported having at least one SA. A total of 1 617
      (75.88%) respondents were identified as NoSH; 446 (20. 93%) as NSSI only; 20
      (0.94%) as SA only, and 48 (2.25%) as NSSI+SA. Psychoticism, extraversion, and
      neuroticism were risk factors for self-harm behaviors. The NSSI+ SA group showed
      significantly higher psychoticism scores than respondents only with NSSI (P<0.
      008 3,d=0. 59). The NSSI+SA group had a higher extraversion score than the NSSI
      group (P>0. 008 3,d=0. 38). CONCLUSION: Personality traits are closely associated
      with self-harm behaviors. Prevention of self harm behaviors should consider
      personality characteristics of middle school students.

PMID- 25571727
TI  - [Progress of ultrasound microbubble contrast technology in the diagnosis and
      treatment of clinical diseases].
AB  - Contrast enhanced ultrasound (CEUS) technology has made important developments
      over the past decade. It has been applied in the clinical diagnosis for various
      diseases of multiple organs including liver, kidney, thyroid, breast and so on,
      which greatly improves the accuracy of ultrasound diagnosis. The emergence of
      targeted ultrasound microbubble makes ultrasound molecular imaging possible. More
      than the improvement of ultrasound imaging, microbubble contrast agent also could
      be an effective drug or gene carrier. Microbubble will rupture under the
      irradiation effect of local ultrasound, and then the carried drugs or genes will
      be released to achieve the purpose of targeted therapy. We should pay more
      attention on the progress of ultrasound microbubble contrast technology in
      clinical and basic research. It will promote better understanding and clinical
      applications of this novel medical ultrasound technology.

PMID- 25571728
TI  - [Enhanced local gene transfection in rats with injured achilles tendons and
      granulation tissues using ultrasound and microbubble].
AB  - OBJECTIVE: To identify best local ukrasound transfection conditions in rats with
      injured achilles tendons and granulation tissues. METHODS: Rat models with
      bilateral injured achilles tendons were established. A mixture of microbubbles
      and enhanced green fluorescent protein (EGFP) plasmids were injected into the
      achilles tendons. The injured tendons were subject to ultrasound irradiation
      under different output intensity, duty cycle and irradiation time. The rats were
      divided into four groups: (1) plasmid+microbubbles- ultrasound (PL+MB+US);
      (2)plasmid + microbubble (PL+MB); (3)plasmid + ultrasound (PL+US); (4) plasmid
      only (PL). We identified the best ultrasound conditions based on the highest
      transfection efficiency in the achilles tendons and granulation tissues and the
      least normal tissue damage. RESULTS: Under the condition of 2 W/cm2 power output
      and 20% duty cycle of ultrasound irradiation for 10 min, EGFP expression was
      demonstrated in the achilles tendons and granulation tissues without showing
      significant damage to normal tissues. Higher levels of EGFP expression were found
      in the group of PL+ MB+ US than the other groups (no significant differences in
      EGFP expression were found among the other three groups). CONCLUSION: Under
      proper conditions, ultrasound and microbubble can enhance in vivo gene
      transfection efficiency in rats with injured achilles tendons and granulation
      tissues without causing obvious normal tissue damage, which could provide a sound
      basis for experimental study of gene therapy for injured tendons.

PMID- 25571729
TI  - [Characteristics of renal occupying lesions in contrast-enhanced
      ultrasonography].
AB  - OBJECTIVE: To determine the value of contrast-enhanced ultrasonography (CEUS) in
      the diagnosis of renal occupying lesions. METHODS: Seventy-eight patients with a
      preliminary diagnosis of renal masses in West China Hospital, Sichuan University
      were examined by CEUS. The characteristics of enhancement, phase of
      enhancement/decline, pseudocapsule sign, and time-intensity curve (TIC) were
      compared between the malignant and benign lesions. RESULTS: Of the 78 renal
      occupying lesions, 50 were malignant and 28 were benign. Malignant lesions showed
      enhanced signs to various degrees. The renal clear cell carcinoma mainly
      presented as "fast wash-in and fast wash-out", while the other malignant lesions
      presented as " slow wash-in and fast wash-out" Pseudocapsule signs were found
      mostly in renal clear cell carcinoma. No enhancement was found in renal cyst.
      Renal angiomyolipoma presented as diffuse hypo-enhancement characterized with
      "slow wash-in and slow wash-out". The time-to-peak (TTP) in malignant lesions
      appeared earlier than benign lesions. Higher levels of peak intensity (PI) and
      area under the curve (AUC) were found in malignant lesions compared with the
      benign lesions (P<0. 05). CONCLUSION: CEUS plus time-intensity curve can provide
      evidence for identifying different kinds of renal occupying lesions.

PMID- 25571730
TI  - [Contrast-enhanced ultrasound parameters for early chronic kidney diseases and
      their associations with laboratory results].
AB  - OBJECTIVE: To determine the value of contrast-enhanced ultrasound (CEUS) for
      assessing renal blood perfusion changes and severity of early chronic kidney
      diseases (CKD). METHODS: The study included 20 patients with clinical diagnosed
      CKD (grade 1-3) (case group) and fifteen normal adults (control group). They were
      given real time CEUS, assessing left renal cortex blood perfusion. We identified
      the time-intensity curve (TIC) parameters that could differentiate participants
      between the two groups, and tested their correlations with glomerular filtration
      rate (eGFR), quantity of urinary protein and cystatin C. RESULTS: Significant
      differences were found in rise time (RT), area under the curve (AUC), time from
      peak to one half, and time to peak (TTP) between the two groups (P< 0.05). eGFR
      was negatively correlated with all of the four TIC parameters (P<0. 05). The
      quantity of urinary protein was positively correlated with three of the four TIC
      parameters (except RT). Cystatin C was positively correlated with all of the four
      TIC parameters (P<0. 05). CONCLUSION: CEUS can detect changes of blood flow
      perfusion in patients with early chronic kidney disease. The perfusion parameters
      are associated with laboratory results reflecting renal damages.

PMID- 25571731
TI  - [Characteristics of carotid atherosclerotic plaques in contrast-enhanced
      ultrasonography of neovascularization].
AB  - OBJECTIVE: To examine the characteristics of carotid arteriosclerotic plaques in
      contrast-enhanced ultrasonography (CEUS) of neovascularization. METHODS: Seventy
      eight patients with carotid atherosclerotic plaques were examined with real-time
      CEUS. The perfusion modes of neovascularization in relation to the carotid
      arteriosclerotic plaques were identified. Patients were categorized into four
      groups according to their plaque echo. Five patients with serious atherosclerotic
      carotid artery disease received carotid endarterectomy. The intra-plaque
      neovascularization recorded by CEUS were validated by post-surgery pathology
      examinations of the tissues. RESULTS: In routing ultrasound examinations, 23 (29.
      49%) plaques were identified with low-echo, 30 (38.46%) with mixed echo, 20 (25.
      64%) with equal-echo, and 5 (6. 41%) with high-echo. The CEUS imaging revealed 60
      carotid atherosclerotic plaques (76. 9%) with various degrees of enhancement in
      intra-plaque neovascularization. The thickness of plaques was correlated with the
      enhanced intensity of ultrasonography, with a Pearson correlation coefficient of
      0. 686 (P < 0. 05). Compared with equal and high echo plaques, the enhanced
      intensity of ultrasonography in low and mixed echo plaques was higher (P<0. 05).
      The intra-plaque neovascularization recorded by CEUS was correlated with the
      grade of neovascularization resulted from post-surgery examinations (Spearman
      coefficient= 0. 886, P 0. 05). CONCLUSION: The real-time CEUS can assess the
      neovascularization in carotid atherosclerotic plaques non-invasively and
      quantitatively.

PMID- 25571732
TI  - [Contrast-enhanced ultrasonography findings for papillary thyroid carcinoma and
      its pathological bases ].
AB  - OBJECTIVE: To investigate the findings of contrast enhanced ultrasound for
      papillary thyroid carcinoma and its pathological bases. METHODS: Seventy two (72)
      patients with thyroid nodules underwent routine conventional ultrasound and color
      Doppler examination, and 86 nodules with TI RADS 3 were examined by contrast
      enhanced ultrasound (CEUS . Histopathological examination was kept as standard
      reference and the findings of CEUS were analyzed. Pathological studies of all
      nodules were made after post-operative CD34 immunohistochemistry staining
      examination. RESULTS: Of the total 86 nodules, Adler CDFl classification grades
      were: grade 0-26. grade I-34. grade II-23 and grade III-3 nodules respectively.
      Enhancement pattern on CEUS showed that there was low enhancement on 71 nodules,
      iso enhancement on 12 and high enhancement on 3 nodules. The differences of echo
      mean intensity. the peak intensity, area under the curve for enhancement
      intensity and CD34 count between the nodules and surrounding tissue were
      statistical significant (P < 0. 001). CONCLUSION: Low enhancement pattern on CEUS
      is the most common finding for papillary thyroid carcinoma, which is related to
      the difference of microvessel density between the nodules and surrounding tissues
      in papillary thyroid carcinoma.

PMID- 25571733
TI  - [Correlation between quantitative results of contrast-enhanced ultrasonography
      and clinical and laboratory indexes for synovium of patients with rheumatoid
      arthritis ].
AB  - OBJECTIVE: To determine the correlation between quantitative results of contrast
      enhanced ultrasound and clinical and laboratory index for synovium of patients
      with rheumatoid arthritis (RA). METHODS: Thirty five RA patients participated in
      this study, with ten normal adults serving as controls. They were given a score
      of DAS28 and underwent laboratory tests, including erythrocyte sedimentation rate
      (ESR) and C-reactive protein (CRP). Contrast-enhanced ultrasound examinations
      were performed to detect thickness of synovium (2D and Power Dopple). RESULTS:
      Peak intensity (PI) and area under the curve (AUC) were positively correlated
      with ESR, CRP and DAS28 score, respectively (P<0. 01). The rest of ultrasound
      parameters had no significant correlations with ESR, CRP and DAS28 score (P>0.
      05). Synovium thickness identified by contrast enhanced ultrasound had
      significant correlations with ESR, CRP and DAS28 score (P < 0. 01). CONCLUSION:
      Synovium thickness determined by contrast enhanced ultrasound, PI and AUC can
      serve as an index estimating inflammatory activity of RA, and provide evidence
      for clinical diagnosis and treatment.

PMID- 25571734
TI  - [The perfusion pattern of lymphadenopathy in contrast-enhanced ultrasonograph.
      under different reference conditions ].
AB  - OBJECTIVE: To determine the perfusion pattern of lymphadenopathy in contrast
      enhanced ultrasonography (CEUS) under different reference conditions. METHODS:
      The CEUS perfusion patterns of 78 superficial lymph node lesions were compared
      with their pathology results. Time-intensity curves were used for comparison
      between benign and malignant lymph nodes. RESULTS: Inhomogeneous hyperenhancement
      was the main perfusion pattern (7/17, 41. 2%) in metastatic lymph nodes; compared
      with homogeneous hyperenhancement (2/4, 50. 0%) in lymphoma, homogeneous
      hyperenhancement and isoenhancement (6/52, 11. 5%) in reactive lymph nodes, and
      circle enhancement (2/4,50. 0%) in tuberculosis. Benign lymph nodes showed
      different mean value, peak intensity and area under the curve compared with their
      surrounding arteries (P<0. 05). But the differences in mean value, rise time,
      time to peak, peak intensity and the area under the curve between benign
      lymphadenopathy and their surrounding tissues were not statistically significant
      (P>0. 05). Malignant lymph nodes showed different mean value and peak intensity
      compared with their surrounding arteries and tissues (P<0. 05). The differences
      in time to peak between malignant lymph nodes and their surrounding tissues were
      also statistically significant (P< 0. 05). CONCLUSION: Different CEUS perfusion
      patterns are associated with different types of lymph node lesions. Time
      intensity curves with surrounding tissues as reference condition offer great
      values for the differential diagnosis of superficial lymphadenopathy.

PMID- 25571735
TI  - [Establishment of experimental abdominal aortic aneurysm model in rats].
AB  - OBJECTIVE: To establish a new reliable experimental abdominal aortic aneurysm
      (AAA) rat model that simulates human aneurysms and has high survival rate.
      METHODS: Twenty-four SD rats were randomly divided equally into two groups (male:
      female=1: 1). Intraluminal saline infusion was given to rats in group A. Rats in
      group B were given intraluminal elastase infusion and extraluminal calcium
      chloride application. The diameter of abdominal aorta was measured and eventually
      harvested at 4 weeks. Successful AAA formation was defined as a dilation ratio
      )50%. HE stain was applied to evaluate the histology changes of aorta. RESULTS:
      Group A had a survival rate, technical success rate and AAA formation rate of 83.
      3%, 91. 67%, and 0% respectively, compared with 91. 67%, 100%, and 90. 91% in
      group B. The AAA formation rate in group B was significantly higher than that in
      group A (P<0. 05). The dilation ratio during infusion was 50. 82% +/-4. 11% in
      group A and 48. 19% +/- 3. 89% in group B. The dilation ratio after infusion was
      29. 55% +/- 4. 69% in group A and 27. 89% + 4. 28% in group B. The difference of
      dilation ratio between the two groups was not significant. The post-surgery (28
      d) dilation ratio was 27. 89% +/- 4. 28%0 in group A and 88. 98% +/- 42. 33% in
      group B (P< 0. 05). Fusiform aneurysms, local adhesion and calcification were
      found in group B. Rats in group B also had thickening intimal, degenerated matrix
      in media, loss of elastin fiber, apoptosis of vascular smooth muscle cells and
      transmural inflammation, none of which was observed in group A. CONCLUSION: With
      improved operative procedure, intraluminal elastase infusion and extraluminal
      calcium chloride application can create reliable AAA rat model.

PMID- 25571736
TI  - [Study on rapid detecting of live Pseudomonas aeruginosa by EMA-PCR].
AB  - OBJECTIVE: To establish a effective and rapid method by Ethidium Monoazide
      Bromide(EMA) in combination with PCR(EMA-PCR) for thedetection of live
      Pseudomrnonas aeruginosa. METHODS: The oprI gene was used as the target gene for
      PCR detection of Pseudomonas aeruginosa , and PCR amplification was carried out
      by utilizing its pure isolates as the template. Sensitivity, EMA concentration
      and exposure time were optimized. RESULTS: The sensitivity of PCR detection was 3
      X 10(3) CFU/mIL, exposure time was 10 min. when the EMA concentration was not
      more than 5 MUg/mLI, no obvious inhibition to the amplification of DNA derived
      from viable bacteria was observed. The PCR amplification of DNA derived from 3 X
      10(6) CFU/mL dead cells could be inhibited effectively by EMA at the final
      concentration of 1 MUg/mL. The results demonstrated the establised method could
      detect 1% live bacteria from a mixed bacterial population. CONCLUSION: EMA-PCR
      can detect live bacteria of Pseudomonas aeruginosa effectively and avoid false
      positive result of the PCR detection.

PMID- 25571738
TI  - [Perinatal management of twins with discordant congenital defects].
AB  - OBJECTIVE: To review the outcomes of perinatal management of twins with
      discordant congenital defects. METHODS: We retrospectively examined the cases of
      twins with discordant congenital defects treated in the West China Second
      University Hospital from December 2011 to December 2013. RESULTS: There were 26
      cases of twins (14 dichorionic and 12 monochorionic) with one anomalous fetus. Of
      those twins, 16 were conceived by nature and 10 by in vitro fertilization and
      embryo tansfer (IVF-ET). Counselling services were offered to the parents by a
      multidisciplinary team about options of pregnancy. Termination of pregnancy was
      chosen on three monochorionic twins. Twelve pairs of twin were delivered at
      26(+3)-37(+6) weeks gestation. One pair ended with neonatal death, and another
      one with gastroschisis was given intrapartum fetal operation. Selective
      termination was chosen on 11 cases using intracardiac injection of potassium
      chloride under ultrasonographic guidance (9 cases) or bipolar cord coagulation (2
      cases). This resulted in ten live births delivered at 25(+5)-38(+4) gustation and
      one neonatal death. CONCLUSION: Early diagnosis of twins with discordant
      congenital defects is important. Multidisciplinary counselling services to
      parents are recommended for determination of options. Intensive prenatal care is
      essential in management of twins with discordant congenital defects.

PMID- 25571737
TI  - [The value of chest X-ray and cervical vascular ultrasound in predicting the
      presence of non-recurrent laryngeal nerves].
AB  - OBJECTIVE: To determine the value of chest X-ray and cervical vascular ultrasound
      in predicting the presence of non-recurrent laryngeal nerves (NRLN) in patients
      with thyroid disorders. METHODS: Preoperative, intraoperative and postoperative
      documents of 2 251 patients with various thyroid disorders between January 2006
      and December 2013 were reviewed. All of the patients underwent preoperative chest
      X-ray examinations. The patients who had confirmed NRLN during surgery were given
      a cervical vascular ultrasound examination postoperatively. RESULTS: A total of
      49 patients (2. 18%, A group) were identified having NRLN by preoperative chest X
      ray as they showed aberrant right subclavian artery (ARSA). Of those suspected
      cases of NRLN, 23 (46.94%) were confirmed during subsequent surgeries and no NRLN
      injury was inflicted. In the 2 202 unsuspected cases (B group), 5 (0. 23%) were
      discovered having NRLN during surgeries, and one (20. 00%) NRLN injury occurred.
      ARSA were found in postoperative cervical vascular ultrasound examination in all
      of the 28 cases of NRLN confirmed during surgeries. The postoperative cervical
      vascular ultrasound suggested a normal right subclavian artery (RSA) for the 26
      chest X-ray revealed but surgically dismissed cases of NRLN. The 23 X-ray
      predicted NRLN were revealed more quickly in surgeries than those that had been
      failed to show in X-ray (t= -18. 867 2, P=O. 000 0). CONCLUSION: Chest X-ray of
      patients scheduled for thyroid surgery should be reviewed carefully and cervical
      vascular ultrasound should be allied for predicting ARSA before surgery.
      Detection of ARSA can accurately predict the existence of NRLN, preventing NRLN
      injury and shorten the duration of subsequent operations.

PMID- 25571739
TI  - [Early diagnosis and prognosis evaluation of Bell palsy with blink reflex ].
AB  - OBJECTIVE: To determine the value of blink reflex in early diagnosis and
      prognosis evaluation of Bell palsy. METHODS: Blink reflex and facial nerve
      conduction were examined in 58 patients with Bell palsy within one week after
      symptom onset. The patients without response of R1 , R2 and R2 ' waves were
      classified as complete efferent retardarce (Group A, 30 cases), and those with
      response of R1 , R2 and R2 ' waves were classified as incomplete efferent
      anomalies (Group B, 28 cases). The clinical outcomes after three months of
      systemic therapy were evaluated using the House-Blackmann (H-B) scale. RESULTS:
      Efferent anomalies of blink reflex occurred in ail of the 58 patients. Abnormal
      results of facial nerve conduction appeared in 23 (39. 7%) patients. The three
      months therapy was effective in 93% patients in Group B and 70% patients in Group
      A (P<0. 05). CONCLUSION: Blink reflex can play a significant role in early
      diagnosis and prognosis evaluation of Bell palsy.

PMID- 25571740
TI  - A framework for inter-level explanations: outlines for a new explanatory
      pluralism.
AB  - According to explanatory pluralism, the appropriate explanatory level is
      determined by pragmatic factors, and there are no general exclusion or preference
      rules concerning higher- or lower-level explanations. While I agree with the
      latter claim, I will argue that the former is in need of revision. In particular,
      I will argue that by distinguishing cases of two explanations being descriptions
      of one underlying causal process, and two explanations being descriptions of two
      distinct causal processes, it becomes clear that the grain size of an explanation
      is in fact determined by the interplay of various pragmatic and non-pragmatic
      factors. Within these constraints, positive guidelines can be developed to direct
      us to the appropriate explanatory level. This gives us the outlines for a general
      framework for classifying various types of relations between explanations on
      different levels. After making a comparison between this new framework and
      standard explanatory pluralism, I end by suggesting some ways in which the
      framework could be further developed.

PMID- 25571741
TI  - Realism, functions, and the a priori: Ernst Cassirer's philosophy of science.
AB  - This paper presents the main ideas of Cassirer's general philosophy of science,
      focusing on the two aspects of his thought that--in addition to being the most
      central ideas in his philosophy of science--have received the most attention from
      contemporary philosophers of science: his theory of the a priori aspects of
      physical theory, and his relation to scientific realism.

PMID- 25571742
TI  - Kant on causal laws and powers.
AB  - The aim of the paper is threefold. Its first aim is to defend Eric Watkins's
      claim that for Kant, a cause is not an event but a causal power: a power that is
      borne by a substance, and that, when active, brings about its effect, i.e. a
      change of the states of another substance, by generating a continuous flow of
      intermediate states of that substance. The second aim of the paper is to argue
      against Watkins that the Kantian concept of causal power is not the pre-critical
      concept of real ground but the category of causality, and that Kant holds with
      Hume that causal laws cannot be inferred non-inductively (that he accordingly has
      no intention to show in the Second analogy or elsewhere that events fall under
      causal laws). The third aim of the paper is to compare the Kantian position on
      causality with central tenets of contemporary powers ontology: it argues that
      unlike the variants endorsed by contemporary powers theorists, the Kantian
      variants of these tenets are resistant to objections that neo-Humeans raise to
      these tenets.

PMID- 25571743
TI  - Philosophy, history and sociology of science: interdisciplinary relations and
      complex social identities.
AB  - Sociology and philosophy of science have an uneasy relationship, while the
      marriage of history and philosophy of science has--on the surface at least--been
      more successful I will take a sociological look at the history of the
      relationships between philosophy and history as well as philosophy and sociology
      of science. Interdisciplinary relations between these disciplines will be
      analysed through social identity complexity theory in oider to draw out some
      conclusions on how the disciplines interact and how they might develop. I will
      use the relationships between the disciplines as a pointer for a more general
      social theory of interdisciplinarity which will then be used to sound a caution
      on how interdisciplinary relations between the three disciplines might be
      managed.

PMID- 25571744
TI  - Unearthing the nation: modern geology and nationalism in Republican China.

PMID- 25571745
TI  - Cultural alterations of Aratus's Phaenomena.

PMID- 25571747
TI  - Introduction: interdisciplinary model exchanges.

PMID- 25571746
TI  - Understanding beyond grasping propositions: a discussion of chess and fish.
AB  - In this paper, we argue that, contra Strevens (2013), understanding in the
      sciences is sometimes partially constituted by the possession of abilities;
      hence, it is not (in such cases) exhausted by the understander's bearing a
      particular psychological or epistemic relationship to some set of structured
      propositions. Specifically, the case will be made that one does not really
      understand why a modeled phenomenon occurred unless one has the ability to
      actually work through (meaning run and grasp at each step) a model simulation of
      the underlying dynamic.

PMID- 25571748
TI  - Maxwell's color statistics: from reduction of visible errors to reduction to
      invisible molecules.
AB  - This paper presents a cross-disciplinary and multi-disciplinary account of
      Maxwell's introduction of statistical models of molecules for the composition of
      gases. The account focuses on Maxwell's deployment of statistical models of data
      in his contemporaneous color researches as established in Cambridge mathematical
      physics, especially by Maxwell's seniors and mentors. The paper also argues that
      the cross-disciplinary, or cross-domain, transfer of resources from the natural
      and social sciences took place in both directions and relied on the complex intra
      disciplinary, or intra-domain, dynamics of Maxwell's researches in natural
      sciences, in color theory, physical astronomy, electromagnetism and dynamical
      theory of gases, as well as involving a variety of types of communicating and
      mediating media, from material objects to concepts, techniques and institutions.

PMID- 25571749
TI  - Varieties of noise: analogical reasoning in synthetic biology.
AB  - The picture of synthetic biology as a kind of engineering science has largely
      created the public understanding of this novel field, covering both its promises
      and risks. In this paper, we will argue that the actual situation is more nuanced
      and complex. Synthetic biology is a highly interdisciplinary field of research
      located at the interface of physics, chemistry, biology, and computational
      science. All of these fields provide concepts, metaphors, mathematical tools, and
      models, which are typically utilized by synthetic biologists by drawing analogies
      between the different fields of inquiry. We will study analogical reasoning in
      synthetic biology through the emergence of the functional meaning of noise, which
      marks an important shift in how engineering concepts are employed in this field.
      The notion of noise serves also to highlight the differences between the two
      branches of synthetic biology: the basic science-oriented branch and the
      engineering-oriented branch, which differ from each other in the way they draw
      analogies to various other fields of study. Moreover, we show that fixing the
      mapping between a source domain and the target domain seems not to be the goal of
      analogical reasoning in actual scientific practice.

PMID- 25571750
TI  - Disciplines, models, and computers: the path to computational quantum chemistry.
AB  - Many disciplines and scientific fields have undergone a computational turn in the
      past several decades. This paper analyzes this sort of turn by investigating the
      case of computational quantum chemistry. The main claim is that the
      transformation from quantum to computational quantum chemistry involved changes
      in three dimensions. First, on the side of instrumentation, small computers and a
      networked infrastructure took over the lead from centralized mainframe
      architecture. Second, a new conception of computational modeling became feasible
      and assumed a crucial role. And third, the field of computa- tional quantum
      chemistry became organized in a market-like fashion and this market is much
      bigger than the number of quantum theory experts. These claims will be
      substantiated by an investigation of the so-called density functional theory
      (DFT), the arguably pivotal theory in the turn to computational quantum chemistry
      around 1990.

PMID- 25571751
TI  - Unification and mechanistic detail as drivers of model construction: models of
      networks in economics and sociology.
AB  - We examine the diversity of strategies of modelling networks in (micro) economics
      and (analytical) sociology. Field-specific conceptions of what explaining (with)
      networks amounts to or systematic preference for certain kinds of explanatory
      factors are not sufficient to account for differences in modelling methodologies.
      We argue that network models in both sociology and economics are abstract models
      of network mechanisms and that differences in their modelling strategies derive
      to a large extent from field-specific conceptions of the way in which a good
      model should be a general one. Whereas the economics models aim at unification,
      the sociological models aim at a set of mechanism schemas that are extrapolatable
      to the extent that the underlying psychological mechanisms are general. These
      conceptions of generality induce specific biases in mechanistic explanation and
      are related to different views of when knowledge from different fields should be
      seen as relevant.

PMID- 25571752
TI  - The birth of classical genetics as the junction of two disciplines: conceptual
      change as representational change.
AB  - The birth of classical genetics in the 1910's was the result of the junction of
      two modes of analysis, corresponding to two disciplines: Mendelism and cytology.
      The goal of this paper is to shed some light on the change undergone by the
      science of heredity at the time, and to emphasize the subtlety of the conceptual
      articulation of Mendelian and cytological hypotheses within classical genetics.
      As a way to contribute to understanding how the junction of the two disciplines
      at play gave birth to a new way of studying heredity, my focus will be on the
      forms of representation used in genetics research at the time. More particularly,
      I will study the design and development, by Thomas H. Morgan's group, of the
      technique of linkage mapping, which embodies the integration of the Mendelian and
      cytological forms of representation. I will show that the design of this
      technique resulted in a genuine conceptual change, which should be described as a
      representational change, rather than merely as the introduction of new hypotheses
      into genetics.

PMID- 25571753
TI  - On the Nose. Before purchasing a diabetes alert dog, read these pointers.

PMID- 25571754
TI  - All for one.

PMID- 25571755
TI  - The great motivator.

PMID- 25571756
TI  - Gift of life.

PMID- 25571758
TI  - Mastering moderation. 7 obstacles to eating sensibly--and how to beat them for
      weight loss.

PMID- 25571757
TI  - Let's talk about ... diabetes.

PMID- 25571759
TI  - Holiday celebrations coast to coast.

PMID- 25571760
TI  - Your AGE limit.

PMID- 25571761
TI  - Chain of events.

PMID- 25571762
TI  - The repertoire of resistance: Non-compliance with directives in Milgram's
      'obedience' experiments.
AB  - This paper is the first extensive conversation-analytic study of resistance to
      directives in one of the most controversial series of experiments in social
      psychology, Stanley Milgram's 1961-1962 study of 'obedience to authority'. As
      such, it builds bridges between interactionist and experimental areas of social
      psychology that do not often communicate with one another. Using as data detailed
      transcripts of 117 of the original sessions representing five experimental
      conditions, I show how research participants' resistance to experimental
      progressivity takes shape against a background of directive/response and
      complaint/remedy conversational sequences--sequence types that project opposing
      and competing courses of action. In local contexts of competing sequential
      relevancies, participants mobilize six forms of resistance to the confederate
      experimenter's directives to continue. These range along a continuum of
      explicitness, from relatively subtle resistance that momentarily postpones
      continuation to techniques for explicitly trying to stop the experiment. Although
      both 'obedient'- and 'defiant'-outcome participants use all six of the forms,
      evidence is provided suggesting precisely how members of the two groups differ in
      manner and frequency of resistance.

PMID- 25571763
TI  - Correlation between corneal and ambient temperature with particular focus on
      polar conditions.
AB  - PURPOSE: To examine the relationship between human corneal and environmental
      temperature. METHODS: An infrared camera was used to measure the corneal surface
      temperature in a group of healthy volunteers as well as in an experimental
      setting with donor corneas and an artificial anterior chamber, employing
      circulating saline at +37 degrees C. Liquid nitrogen was used to obtain a very
      low temperature in the experimental setting. High ambient temperature
      measurements were performed in a sauna. RESULTS: In healthy volunteers, the
      cornea required at least 20-30 min to adapt to change in ambient temperature. The
      relationship between corneal and external temperature was relatively linear. At
      the two extremes, +83 degrees C and -40 degrees C, the corneal temperature was
      +42 degrees C and +25.1 degrees C, respectively. In the experimental setting,
      corneal temperature was +24.3 degrees C at air temperature -40 degrees C.
      CONCLUSION: A rather stable aqueous humour temperature of +37 degrees C and high
      thermal conductivity of the corneal tissue prevent corneal frostbite even at
      extremely low ambient temperatures.

PMID- 25571764
TI  - Normalizing dysfunctional purine metabolism accelerates diabetic wound healing.
AB  - Diabetic patients exhibit dysfunction of the normal wound healing process,
      leading to local ischemia by vascular occlusive disease as well as sustained
      increases in the proinflammatory cytokines and overproduction of reactive oxygen
      species (ROS). Of the many sources of ROS, the enzyme xanthine oxidase (XO) has
      been linked to overproduction of ROS in diabetic environment, and studies have
      shown that treatment with XO inhibitors decreases XO overactivity and XO
      generated ROS. This study evaluates the role of XO in the diabetic wound and the
      impact of specifically inhibiting its activity on wound healing. Treatment of
      diabetic wounds with siXDH (xanthine dehydrogenase siRNA) decreased XDH mRNA
      expression by 51.6%, XO activity by 35.9%, ROS levels by 78.1%, pathologic wound
      burden by 31.5%, and accelerated wound healing by 7 days (23.3%). Polymerase
      chain reaction analysis showed that increased XO activity in wild-type wound may
      be due to XDH to XO conversion and/or XO phosphorylation, but not to gene
      transcription, whereas increased XO activity in diabetic wounds may also be from
      gene transcription. These results suggest that XO may be responsible for large
      proportion of elevated oxidative stress in the diabetic wound environment and
      that normalizing the metabolic activity of XO using targeted delivery of siXDH
      may decrease overproduction of ROS and accelerate wound healing in diabetic
      patients. 

PMID- 25571765
TI  - Clinical clues for differential diagnosis between verruca plana and verruca plana
      like seborrheic keratosis.
AB  - Sometimes the clinical differentiation between verruca plana (VP) and VP-like
      seborrheic keratosis (SK) could be challenged. However, there have been no
      studies on this issue to date. The aim of this study was to elucidate clinical
      and dermoscopic differences between these two diseases, and also to suggest a
      diagnostic algorithm of VP and VP-like SK without skin biopsy. The patients who
      had lesions clinically considered as VP or VP-like SK were the target of our
      study. We took clinical and dermoscopic photos with informed consent and
      conducted a questionnaire. All patients had their diagnoses confirmed by biopsy.
      Thirty-three patients were enrolled in our study. Seventeen patients were finally
      diagnosed with VP (51.5%) and 16 patients with VP-like SK (48.5%). In clinical
      findings, VP-like SK showed significantly more scattered distribution than VP (P
      = 0.039), which exhibited more clustered or grouped distribution (P = 0.039). In
      dermoscopic findings, brain-like appearance was more commonly observed in VP-like
      SK (P = 0.003) whereas VP showed more red dots or globular vessels (P = 0.017)
      and even-colored light brown to yellow patch (P < 0.001). Sex, onset age, the
      size of each lesion, location, color and shape showed no significant differences
      between them (P > 0.05). Based on our results, we suggest a diagnostic algorithm
      using Koebner's phenomenon, dermoscopic findings, distribution of each lesion and
      biopsy for multiple VP-like lesions in adults, and we think it will be a very
      useful diagnostic tool in daily clinical dermatological practice.

PMID- 25571766
TI  - Tetrahydroxystilbene glucoside improves TNF-alpha-induced endothelial
      dysfunction: involvement of TGFbeta/Smad pathway and inhibition of vimentin
      expression.
AB  - Endothelial dysfunction plays an important role in the pathogenesis of
      atherogenesis. 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), an
      active component of the rhizome extract from Polygonum multiflorum (PM), exhibits
      significant anti-atherosclerotic activity. Here, we used human umbilical vein
      endothelial cells (HUVECs) induced by tumor necrosis factor-alpha (TNF-alpha) in
      vitro to investigate the cytoprotective effects of TSG on TNF-alpha-induced
      endothelial injury and the related mechanisms. Pretreatment with 50 and 100 MUM
      TSG markedly attenuated TNF-alpha-induced loss of cell viability and release of
      lactate dehydrogenase (LDH) and inhibited TNF-alpha-induced cell apoptosis. The
      inhibition of vimentin expression was involved in the cytoprotection afforded by
      TSG. Using inhibitors for PI3K and TGFbeta or siRNA for Akt and Smad2, we found
      that vimentin production in HUVECs is regulated by TGFbeta/Smad signaling, but
      not by PI3K-Akt-mTOR signaling. Meanwhile, TSG inhibited both the expression of
      TGFbeta1 and the phosphorylation of Smad2 and Smad3, and TSG suppressed the
      nuclear translocation of Smad4 induced by TNF-alpha. These results suggest that
      TSG protects HUVECs against TNF-alpha-induced cell damage by inhibiting vimentin
      expression via the interruption of the TGFbeta/Smad signaling pathway. 

PMID- 25571767
TI  - The relationship with the ambulance clinicians as experienced by significant
      others.
AB  - BACKGROUND: Interpersonal relationships between clinicians and patients are
      important aspects of the ambulance care, requiring a balance between objectified
      acute medical treatment and a holistic care. Being a significant other (SO) in
      the ambulance care setting is described as being caught between hope and dread.
      Little research has focused on SOs' experiences of the relationship with the
      ambulance clinicians. AIM: To elucidate meanings of the relationship with the
      clinicians in the ambulance care setting as experienced by the patients' SOs.
      DESIGN: Qualitative lifeworld design. METHODS: Data was collected using open
      ended interviews with nine SOs. The verbatim transcribed interviews were analysed
      with a phenomenological hermeneutic method. FINDINGS: The structural analysis
      resulted in one main theme: 'Being lonely together'. The main theme comprises
      three themes: 'Being in a shared struggle', 'To hand over the affected person in
      trust' and 'Being the second person in focus' and six subthemes. The main theme
      is for the SOs to share the struggles of the affected person with the ambulance
      clinicians and to be comforted while handing over the responsibility for the
      affected person. Hence the SO is excluded and lonely and on his/her own, while
      not the primary focus of the ambulance clinicians. CONCLUSIONS: The relationship
      with the ambulance clinicians from the perspective of the SOs can be understood
      as complex, involving both being lonely and together at the same time. The
      findings support a holistic approach towards the ambulance care involving SOs.
      RELEVANCE FOR CLINICAL PRACTICE: This study outlines the importance of an
      emergency ambulance care involving SOs as affected persons and supports a balance
      between emergency medical treatment to the patient and a holistic care, involving
      the SOs' suffering.

PMID- 25571768
TI  - Biodrying for municipal solid waste: volume and weight reduction.
AB  - Biodrying is a variation of aerobic decomposition used for the mechanical
      biological treatment organic substances to dry and partially stabilize residual
      municipal waste. This study focuses on the volume and weight reduction
      biodegradation of the biodrying process using municipal solid waste and the
      appearance of a stable, final product. The materials were placed in a reactor
      with invariant airflow rates of 50 L/h and initial moisture contents of 48.49
      50.00%. The laboratory-scale experiments were implemented using a 36-L biodrying
      reactor equipped with an air supply system, a biomass temperature sensor and air
      sensors. To determine the effect of temperature on biodrying, the process was
      repeated at various temperatures between 30  degrees C and 50  degrees C. The
      results obtained indicated that after 13 days, biodrying reduced the volume
      content of waste by 32% and the final product had a high calorific value (4680
      kcal/kg). 

PMID- 25571769
TI  - Efficacy of selective laser trabeculoplasty for normal tension glaucoma: 1 year
      results.
AB  - BACKGROUND: Normal tension glaucoma (NTG) is commonly treated with anti-glaucoma
      medications. Recently, selective laser trabeculoplasty (SLT) has been
      demonstrated to lower the intraocular pressure (IOP) and medication use in NTG.
      The purpose of this study was to investigate the efficacy of a single session of
      SLT for NTG at 1 year. METHODS: This prospective cohort study recruited NTG
      patients taking anti-glaucoma medication. Potential subjects were excluded if
      they had had previous glaucoma surgery or laser and also if intraocular surgery
      or additional SLT procedures were performed after the first treatment. All
      subjects underwent a 1-month washout. A 30% IOP reduction was set as the target
      IOP. A single session of SLT was performed to 360 degrees of the trabecular
      meshwork. At 1-month after SLT, medication was resumed to achieve the target IOP.
      The IOP was measured every 3 months, and the number of medications was recorded
      at 3, 6, and 12 months. Only the right eye was used for statistical analysis.
      RESULTS: In 41 right eyes, the mean pre-study IOP was 14.3 +/- 3.4 mmHg while on
      1.5 +/- 0.8 eye drops. The post-washout IOP was 16.2 +/- 2.2 mmHg. A mean of
      191.1 +/- 26.3 SLT shots at 1.0 +/- 0.07 mJ were applied. There was significant
      IOP reduction at all time intervals following SLT when compared to the post
      washout IOP (P < 0.0001). The number of medications was significantly reduced at
      all time intervals following SLT when compared to the pre-study level (P <
      0.0001). At 12 months, the mean IOP was 12.2 +/- 2.2 mmHg while on 1.1 +/- 0.9
      eye drops. CONCLUSIONS: A single session of SLT for NTG achieved an additional
      15% IOP reduction while using 27% less medication at 1 year compared to pre-study
      levels. TRIAL REGISTRATION: The Clinical Trials Register of the University of
      Hong Kong HKCTR1847 The European Clinical Trials Database 2014-003305-15 (August
      11, 2014) ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014
      003305-15 ).

PMID- 25571770
TI  - Visual imagery influences brain responses to visual stimulation in bilateral
      cortical blindness.
AB  - Mental imagery is a powerful mechanism that may facilitate visual perception as
      well as compensate for it. The role of V1 in mental imagery is still a matter of
      debate. Our goal here was to investigate whether visual imagery was still
      possible in case of bilateral V1 destruction behaviorally evidenced by total
      clinical blindness and if so, whether it might boost residual visual perception.
      In a factorial fMRI design, faces, scenes or scrambled images were presented
      while a rare patient with cortical blindness over the whole visual field due to
      bilateral V1-lesions (TN) was instructed to imagine either an angry person or a
      neutral object (tree). The results show that visual imagery of a person activates
      frontal, parietal and occipital brain regions similar to control subjects and
      hence suggest that V1 is not necessary for visual imagery. In addition, the
      combination of visual stimulation and visual imagery of socio-emotional stimuli
      triggers activation in superior parietal lobule (SPL) and ventromedial (vmPFC)
      and dorsolateral prefrontal cortex (DLPFC). Finally, activation during residual
      vision, visual imagery and their interaction overlapped in the SPL, arguing for a
      central role of feeling in V1-independent vision and imagery. 

PMID- 25571771
TI  - The complexities of lesion-deficit inference in the human brain: reply to Herbet
      et al.

PMID- 25571772
TI  - Shedding light on tics.

PMID- 25571773
TI  - Longitudinal measurement invariance of the Beck Scale for Suicide Ideation.
AB  - In mental health care, both clinical and scientific decisions are based on within
      subject comparisons of test scores on the same self-report questionnaire at
      different points in time. To establish the validity of test score comparisons
      over time, longitudinal measurement invariance should be established. The current
      study tested whether the 19 item Beck Scale for Suicide Ideation (BSS) is
      measurement invariant (MI) over time. As the first five items of the scale are
      often used to screen for the presence of suicidal thoughts, we also tested a
      model consisting of only the first five items. Psychiatric in- and out-patients
      (n=475) completed the questionnaire upon admission and after 3 months. By means
      of confirmatory factor analysis (CFA) we tested whether the parameters of a
      single factor model were equal over time. All fit indices indicated that both the
      19-item questionnaire and the five-item screener were measurement invariant over
      time. This means that changes in test-scores over time can be attributed to true
      changes in the construct of interest. These findings legitimate the use of the 19
      item scale and the five-item screener in longitudinal assessments. 

PMID- 25571774
TI  - Technical modifications in the repair of acute ischemic posterior ventricular
      septal defect without ventriculotomy.
AB  - OBJECTIVE: Transventricular repair for acute ischemic posterior ventricular
      septal defect is challenging and is associated with high operative morbidity and
      mortality. We have adopted the alternative technique of transatrial repair and
      recently have added technical modifications that result in less residual or
      recurrent septal shunt. This study reports those modifications and the related
      outcomes. METHODS: Retrospective review of 10 patients with acute ischemic
      posterior ventricular septal defect operated from November 2006 through March
      2013. The septal defect was repaired through the right atrium with a prosthetic
      patch. Interlocking sutures and an additional continuous suture line buttress
      around the perimeter of the patch were added to the repair in four (40%)
      patients. RESULTS: Killip class IV heart failure was present in nine (90%) of the
      patients, and all received preoperative intra-aortic balloon pump therapy. No
      patient who received the recent technical modifications experienced a residual or
      recurrent shunt. However, three (50%) patients who did not undergo this
      modification developed either a residual septal shunt (n = 1), an early recurrent
      septal shunt (n = 1), or a ventricular rupture (n = 1). There was no 30-day or in
      hospital mortality after surgery, but a single patient died two years after
      operation due to congestive heart failure. The remaining patients are alive after
      surgery at a median of 2.0 years. CONCLUSIONS: The transatrial repair of an acute
      ischemic posterior ventricular septal defect is a safe technique. The addition of
      interlocking pledgetted sutures and a patch suture line buttress decreases the
      incidence of residual and recurrent septal shunt.

PMID- 25571775
TI  - Leptin in depressive episodes: is there a difference between unipolar and bipolar
      depression?
AB  - OBJECTIVE: The present study investigated whether peripheral leptin levels are
      associated with current depressive episodes in a cross-sectional study nested
      within a population-based study. METHODS: The Mini-International Neuropsychiatric
      Interview (MINI) 5.0 was used to assess the presence of current depressive
      episodes. The sample was composed of 206 subjects (103 controls and 103 subjects
      with a current depressive episode) paired by gender, BMI and age. Medication use
      and lifestyle characteristics were self-reported. RESULTS: Serum leptin levels
      were lower in currently depressive subjects (10.9 +/- 12.0 ng/ml) than in the
      control group (20.3 +/- 24.0 ng/ml; p = 0.023). According to the clinical
      diagnosis, individuals with bipolar depression present lower leptin levels (8.4
      +/- 8.1 ng/ml) than those with unipolar depression (12.0 +/- 13.4 ng/ml) and the
      control group (20.3 +/- 24.0 ng/ml; p = 0.031). In addition, ANCOVA showed that
      leptin is an independent factor associated with current depressive episodes (p =
      0.018). CONCLUSION: A decreased leptin level might be a useful peripheral marker
      associated with depressive episodes in the context of bipolar disorder.

PMID- 25571776
TI  - Easy as ABCABC: Abstract Language Facilitates Performance on a Concrete
      Patterning Task.
AB  - The labels used to describe patterns and relations can influence children's
      relational reasoning. In this study, 62 preschoolers (Mage  = 4.4 years) solved
      and described eight pattern abstraction problems (i.e., recreated the relation in
      a model pattern using novel materials). Some children were exposed to concrete
      labels (e.g., blue-red-blue-red) and others were exposed to abstract labels
      (e.g., A-B-A-B). Children exposed to abstract labels solved more problems
      correctly than children exposed to concrete labels. Children's correct adoption
      of the abstract language into their own descriptions was particularly beneficial.
      Thus, using concrete learning materials in combination with abstract
      representations can enhance their utility for children's performance.
      Furthermore, abstract language may play a key role in the development of
      relational thinking. 

PMID- 25571777
TI  - Introduction of the transtheoretical model and organisational development theory
      in weight management: A narrative review.
AB  - Overweight and obesity are serious public health and medical problems among
      children and adults worldwide. Behavioural change has been demonstrably
      contributory to weight management programs. Behavioural change-based weight loss
      programs require a theoretical framework. We will review the transtheoretical
      model and the organisational development theory in weight management. The
      transtheoretical model is a behaviour theory of individual level frequently used
      for weight management programs. The organisational development theory is a more
      complicated behaviour theory that applies to behavioural change on the system
      level. Both of these two theories have their respective strengths and weaknesses.
      In this manuscript, we try to introduce the transtheoretical model and the
      organisational development theory in the context of weight loss programs among
      population that are overweight or obese. Ultimately, we wish to present a new
      framework/strategy of weight management by integrating these two theories
      together. 

PMID- 25571778
TI  - Nine-year follow-up in a child with chromosomal integration of human herpesvirus
      6 transmitted from an unrelated donor through the Japan Marrow Donor Program.

PMID- 25571779
TI  - Do you see what I see? Insights from using google glass for disaster telemedicine
      triage.
AB  - INTRODUCTION: Disasters are high-stakes, low-frequency events. Telemedicine may
      offer a useful adjunct for paramedics performing disaster triage. The objective
      of this study was to determine the feasibility of telemedicine in disaster
      triage, and to determine whether telemedicine has an effect on the accuracy of
      triage or the time needed to perform triage. METHODS: This is a feasibility study
      in which an intervention team of two paramedics used the mobile device Google
      Glass (Google Inc; Mountain View, California USA) to communicate with an off-site
      physician disaster expert. The paramedic team triaged simulated disaster victims
      at the triennial drill of a commercial airport. The simulated victims had
      preassigned expected triage levels. The physician had an audio-video interface
      with the paramedic team and was able to observe the victims remotely. A control
      team of two paramedics performed disaster triage in the usual fashion. Both teams
      used the SMART Triage System (TSG Associates LLP; Halifax, England), which
      assigns patients into Red, Yellow, Green, and Black triage categories. The
      paramedics were video recorded, and their time required to triage was logged. It
      was determined whether the intervention team and the control team varied
      regarding accuracy of triage. Finally, the amount of time the intervention team
      needed to triage patients when telemedicine was used was compared to when that
      team did not use telemedicine. RESULTS: The two teams triaged the same 20
      patients. There was no significant difference between the two groups in overall
      triage accuracy (85.7% for the intervention group vs 75.9% for the control group;
      P = .39). Two patients were triaged with telemedicine. For the intervention
      group, there was a significant difference in time to triage patients with
      telemedicine versus those without telemedicine (35.5 seconds; 95% CI, 72.5-143.5
      vs 18.5 seconds; 95% CI, 13.4-23.6; P = .041). CONCLUSION: There was no increase
      in triage accuracy when paramedics evaluating disaster victims used telemedicine,
      and telemedicine required more time than conventional triage. There are a number
      of obstacles to available technology that, if overcome, might improve the utility
      of telemedicine in disaster response.

PMID- 25571781
TI  - Conditions simulating androgenetic alopecia.
AB  - Androgenetic alopecia is a common form of hair loss, characterized by a
      progressive hair follicular miniaturization, caused by androgen hormones on a
      genetically susceptible hair follicle, in androgenic-dependent areas.
      Characteristic phenotype of androgenetic alopecia is also observed in many other
      hair disorders. These disorders are androgenetic-like diseases that cause many
      differential diagnosis or therapeutic error problems. The objective of this
      review was to systematically analyse the greatest number of conditions that mimic
      the AGA pattern and explain their disease pathogenesis. 

PMID- 25571782
TI  - P=O functional group-containing cryptands: from supramolecular complexes to
      poly[2]pseudorotaxanes.
AB  - Two types of cryptand-based host-guest complexes were constructed successfully,
      in which P=O functional groups were located at the different positions of the
      third arms. Consequently, supramolecular poly[2]pseudorotaxanes with almost
      linear and zigzag shapes were formed in the solid state.

PMID- 25571780
TI  - Activation of toll like receptor 4 attenuates GABA synthesis and postsynaptic
      GABA receptor activities in the spinal dorsal horn via releasing interleukin-1
      beta.
AB  - Toll like receptor 4 (TLR4) is an innate immune pattern recognition receptor,
      expressed predominantly on microglia in the CNS. Activation of spinal TLR4 plays
      a critical role in the genesis of pathological pain induced by nerve injury, bone
      cancer, and tissue inflammation. Currently, it remains unknown how synaptic
      activities in the spinal dorsal horn are regulated by TLR4 receptors. Through
      recording GABAergic currents in neurons and glial glutamate transporter currents
      in astrocytes in rodent spinal slices, we determined whether and how TLR4
      modulates GABAergic synaptic activities in the superficial spinal dorsal horn. We
      found that activation of TLR4 by lipopolysaccharide (LPS) reduces GABAergic
      synaptic activities through both presynaptic and postsynaptic mechanisms.
      Specifically, LPS causes the release of IL-1beta from microglia. IL-1beta in turn
      suppresses GABA receptor activities at the postsynaptic site through activating
      protein kinase C (PKC) in neurons. GABA synthesis at the presynaptic site is
      reduced upon activation of TLR4. Glial glutamate transporter activities are
      suppressed by IL-1beta and PKC activation induced by LPS. The suppression of
      glial glutamate transporter activities leads to a deficiency of glutamine supply,
      which results in an attenuation of the glutamate-glutamine cycle-dependent GABA
      synthesis. These findings shed light on understanding synaptic plasticity induced
      by activation of TLR4 under neuroinflammation and identify GABA receptors, glial
      glutamate transporters, IL-1beta and PKC as therapeutic targets to abrogate
      abnormal neuronal activities following activation of TLR4 in pathological pain
      conditions. 

PMID- 25571785
TI  - Early identification of women with HELLP syndrome who need plasma exchange after
      delivery.
AB  - OBJECTIVES: To compare the laboratory course of HELLP syndrome between patients
      who recover and those who progress to postpartum thrombotic microangiopathic
      syndrome (PTMS) and require postpartum plasma exchange (PPEX) and to describe
      maternal characteristics and morbidity in women with PTMS. METHODS: In this
      retrospective analysis, 81 patients recovered and 5 progressed. Values for
      aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin,
      platelets (Plt), urea, and creatinine at 0, 8, 16, 24, 48, and 72 hours
      postpartum in both groups were analyzed and compared. We also described maternal
      characteristics and morbidity of patients who progressed to PTMS. RESULTS:
      Patient groups differed significantly at 72 hours postpartum for Plt and LDH
      values and at 24 and 48 hours for bilirubin. Trends for AST and Plt differed
      significantly between the recovery and progression groups in the first 48 hours.
      Patients who progressed had acute kidney injury and other severe maternal
      morbidity, including one case of maternal death. CONCLUSIONS: Women with HELLP
      syndrome without clear Plt and AST improvement in the first 48 hours and with
      acute kidney injury, neurological impairment, or respiratory distress syndrome
      are at risk of progressing to PTMS. They should be administered PPEX between 24
      and 72 hours postpartum.

PMID- 25571783
TI  - Protein tyrosine phosphatase receptor type R is required for Purkinje cell
      responsiveness in cerebellar long-term depression.
AB  - BACKGROUND: Regulation of synaptic connectivity, including long-term depression
      (LTD), allows proper tuning of cellular signalling processes within brain
      circuitry. In the cerebellum, a key centre for motor coordination, a positive
      feedback loop that includes mitogen-activated protein kinases (MAPKs) is required
      for proper temporal control of LTD at cerebellar Purkinje cell synapses. Here we
      report that the tyrosine-specific MAPK-phosphatase PTPRR plays a role in
      coordinating the activity of this regulatory loop. RESULTS: LTD in the cerebellum
      of Ptprr (-/-) mice is strongly impeded, in vitro and in vivo. Comparison of
      basal phospho-MAPK levels between wild-type and PTPRR deficient cerebellar slices
      revealed increased levels in mutants. This high basal phospho-MAPK level
      attenuated further increases in phospho-MAPK during chemical induction of LTD,
      essentially disrupting the positive feedback loop and preventing alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) phosphorylation and
      endocytosis. CONCLUSIONS: Our findings indicate an important role for PTPRR in
      maintaining low basal MAPK activity in Purkinje cells. This creates an optimal
      'window' to boost MAPK activity following signals that induce LTD, which can then
      propagate through feed-forward signals to cause AMPAR internalization and LTD.

PMID- 25571784
TI  - Light-responsive nanoparticle depot to control release of a small molecule
      angiogenesis inhibitor in the posterior segment of the eye.
AB  - Therapies for macular degeneration and diabetic retinopathy require intravitreal
      injections every 4-8 weeks. Injections are uncomfortable, time-consuming, and
      carry risks of infection and retinal damage. However, drug delivery via
      noninvasive methods to the posterior segment of the eye has been a major
      challenge due to the eye's unique anatomy and physiology. Here we present a novel
      nanoparticle depot platform for on-demand drug delivery using a far ultraviolet
      (UV) light-degradable polymer, which allows noninvasively triggered drug release
      using brief, low-power light exposure. Nanoparticles stably retain encapsulated
      molecules in the vitreous, and can release cargo in response to UV exposure up to
      30 weeks post-injection. Light-triggered release of nintedanib (BIBF 1120), a
      small molecule angiogenesis inhibitor, 10 weeks post-injection suppresses
      choroidal neovascularization (CNV) in rats. Light-sensitive nanoparticles are
      biocompatible and cause no adverse effects on the eye as assessed by
      electroretinograms (ERG), corneal and retinal tomography, and histology.

PMID- 25571787
TI  - Plerixafor in the treatment of progenitor cell mobilization failure: First
      experience in Algeria.

PMID- 25571786
TI  - Triglyceride accumulation inhibitory effects of new chromone glycosides from
      Drynaria fortunei.
AB  - Two new chromone glycosides, drynachromosides C (1) and D (2), along with five
      known chromones (3-7), were isolated from the rhizomes of Drynaria fortunei. The
      structures of the two new compounds were elucidated on the basis of physico
      chemical property and spectroscopic data. Triglyceride (TG) accumulation
      inhibitory effects of the obtained chromones on 3T3-L1 cells were investigated.
      The results showed that 1, 2 and 5 exhibited inhibitory activity on TG
      accumulation. Effects of compounds 1 and 2 on mRNA expression of PPARgamma,
      C/EBPalpha and aP2 in 3T3-L1 cells were also investigated. 

PMID- 25571788
TI  - Natural killer cells: In health and disease.
AB  - Natural killer (NK) cells constitute our bodies' frontline defense system,
      guarding against tumors and launching attacks against infections. The activities
      of NK cells are regulated by the interaction of various receptors expressed on
      their surfaces with cell surface ligands. While the role of NK cells in
      controlling tumor activity is relatively clear, the fact that they are also
      linked to various other disease conditions is now being highlighted. Here, we
      present an overview of the role of NK cells during normal body state as well as
      under diseased state. We discuss the possible utilization of these powerful cells
      as immunotherapeutic agents in combating diseases such as asthma, autoimmune
      diseases, and HIV-AIDS. This review also outlines current challenges in NK cell
      therapy. 

PMID- 25571789
TI  - MiR-125b and miR-99a encoded on chromosome 21 co-regulate vincristine resistance
      in childhood acute megakaryoblastic leukemia.

PMID- 25571790
TI  - Application of digital tomosynthesis in diagnosing the fractures or dislocations
      in irregular bones and regions with complex structures.
AB  - OBJECTIVE: The application potential of digital tomosynthesis in diagnosing
      fractures or dislocations in irregular bones and regions with complex structures
      was evaluated. METHODS: Digital radiography and tomosynthesis were performed in
      121 patients, and the image quality, accuracy, sensitivity, and specificity were
      compared. RESULTS: The number of participants with a definite diagnosis of
      fracture and/or dislocation was 98. The ratio of excellent images, accuracy,
      sensitivity, and specificity of digital tomosynthesis were higher than that of
      direct radiography. CONCLUSION: Digital tomosynthesis could be applied in the
      diagnosis of fractures or dislocations in irregular bones and regions with
      complex structures.

PMID- 25571791
TI  - Computed tomographic features predictive of local recurrence in patients with
      early stage lung cancer treated with stereotactic body radiation therapy.
AB  - INTRODUCTION: The objective of this study is to identify computed tomography (CT)
      features of local recurrence (LR) after stereotactic body radiation therapy
      (SBRT) for lung cancer. METHODS: Two hundred eighteen patients underwent SBRT for
      lung cancer from January 1st, 2006 to March 1st, 2011. Signs of LR recorded:
      opacity with new bulging margin, opacification of air bronchograms, enlarging
      pleural effusion, new or enlarging mass, and increased lung density at the
      treatment site. RESULTS: A new bulging margin at the treatment site was the only
      feature significantly associated with LR (P<.005). CONCLUSION: Most CT features
      classically associated with LR following conventional radiation therapy are
      unreliable for predicting LR following SBRT.

PMID- 25571792
TI  - Has reducing fine particulate matter and ozone caused reduced mortality rates in
      the United States?
AB  - PURPOSE: Between 2000 and 2010, air pollutant levels in counties throughout the
      United States changed significantly, with fine particulate matter (PM2.5)
      declining over 30% in some counties and ozone (O3) exhibiting large variations
      from year to year. This history provides an opportunity to compare county-level
      changes in average annual ambient pollutant levels to corresponding changes in
      all-cause (AC) and cardiovascular disease (CVD) mortality rates over the course
      of a decade. Past studies have demonstrated associations and subsequently either
      interpreted associations causally or relied on subjective judgments to infer
      causation. This article applies more quantitative methods to assess causality.
      METHODS: This article examines data from these "natural experiments" of changing
      pollutant levels for 483 counties in the 15 most populated US states using
      quantitative methods for causal hypothesis testing, such as conditional
      independence and Granger causality tests. We assessed whether changes in
      historical pollution levels helped to predict and explain changes in CVD and AC
      mortality rates. RESULTS: A causal relation between pollutant concentrations and
      AC or CVD mortality rates cannot be inferred from these historical data, although
      a statistical association between them is well supported. There were no
      significant positive associations between changes in PM2.5 or O3 levels and
      corresponding changes in disease mortality rates between 2000 and 2010, nor for
      shorter time intervals of 1 to 3 years. CONCLUSIONS: These findings suggest that
      predicted substantial human longevity benefits resulting from reducing PM2.5 and
      O3 may not occur or may be smaller than previously estimated. Our results
      highlight the potential for heterogeneity in air pollution health effects across
      regions, and the high potential value of accountability research comparing model
      based predictions of health benefits from reducing air pollutants to historical
      records of what actually occurred.

PMID- 25571793
TI  - Identifying gene clusters by discovering common intervals in indeterminate
      strings.
AB  - BACKGROUND: Comparative analyses of chromosomal gene orders are successfully used
      to predict gene clusters in bacterial and fungal genomes. Present models for
      detecting sets of co-localized genes in chromosomal sequences require prior
      knowledge of gene family assignments of genes in the dataset of interest. These
      families are often computationally predicted on the basis of sequence similarity
      or higher order features of gene products. Errors introduced in this process
      amplify in subsequent gene order analyses and thus may deteriorate gene cluster
      prediction. RESULTS: In this work, we present a new dynamic model and efficient
      computational approaches for gene cluster prediction suitable in scenarios
      ranging from traditional gene family-based gene cluster prediction, via multiple
      conflicting gene family annotations, to gene family-free analysis, in which gene
      clusters are predicted solely on the basis of a pairwise similarity measure of
      the genes of different genomes. We evaluate our gene family-free model against a
      gene family-based model on a dataset of 93 bacterial genomes. CONCLUSIONS: Our
      model is able to detect gene clusters that would be also detected with well
      established gene family-based approaches. Moreover, we show that it is able to
      detect conserved regions which are missed by gene family-based methods due to
      wrong or deficient gene family assignments.

PMID- 25571794
TI  - Structure-based design and optimization of potent inhibitors of the adenoviral
      protease.
AB  - Adenoviral infections are associated with a wide range of acute diseases, among
      which ocular viral conjunctivitis (EKC) and disseminated disease in
      immunocompromised patients. To date, no approved specific anti-adenoviral drug is
      available, but there is a growing need for an effective treatment of such
      infections. The adenoviral protease, adenain, plays a crucial role for the viral
      lifecycle and thus represents an attractive therapeutic target. Structure-guided
      design with the objective to depeptidize tetrapeptide nitrile 1 led to the novel
      chemotype 2. Optimization of scaffold 2 resulted in picomolar adenain inhibitors
      3a and 3b. In addition, a complementary series of irreversible vinyl sulfone
      containing inhibitors were rationally designed, prepared and evaluated against
      adenoviral protease. High resolution X-ray co-crystal structures of
      representatives of each series proves the successful design of these inhibitors
      and provides an excellent basis for future medicinal chemistry optimization of
      these compounds. 

PMID- 25571795
TI  - Synthesis and cytotoxicity evaluation of 4-amino-4-dehydroxylarctigenin
      derivatives in glucose-starved A549 tumor cells.
AB  - The natural product arctigenin (ATG) demonstrated preferential cytotoxicity to
      cancer cells under glucose starvation. A series of 4-amino-4-dehydroxylarctigenin
      derivatives based on lead compound ATG were designed and synthesized by
      bioisosteric modifications. Their cytotoxicities were evaluated in glucose
      starved A549 tumor cells and the results indicated that the 4-amino-4
      dehydroxylarctigenin showed more potent cytotoxicity than arctigenin, and the
      further substituent group on 4-amino would result in the cytotoxicities decreased
      significantly. 4-Substituted-arctigenin could selectively target on glucose
      starved A549 tumor cells which provide an alternative strategy for anticancer
      drug development with minimal normal tissue toxicity. 

PMID- 25571796
TI  - New Chief Dental Officer: a changed role.

PMID- 25571797
TI  - Infectious disease: early syphilis.

PMID- 25571798
TI  - Defensive dentistry: not only the young.

PMID- 25571799
TI  - Orthodontics: fast and furious.

PMID- 25571800
TI  - Periodontology: disease group.

PMID- 25571801
TI  - From the archive: blood and thunder dentistry.

PMID- 25571803
TI  - Do dentures improve quality of life?

PMID- 25571807
TI  - Dentists rebel against regulator.

PMID- 25571811
TI  - Dental teams encouraged to support No Smoking Day.

PMID- 25571813
TI  - The denture box. An aid to denture hygiene.
AB  - This paper re-visits the need for patients or their carers to maintain as low a
      level of denture biofilm as possible. It notes that the handling of dentures is
      unpleasant to carers and suggests a method of reducing this contact to a minimum
      but yet allow efficient cleaning by means of brushing. It also highlights the
      potential damage that can occur due to mishandling or accident. The denture box
      acts as a safe storage unit and finally, it suggests that its 'footprint' allows
      accurate recovery in an institution where dentures can be inadvertently mingled. 

PMID- 25571814
TI  - Brief advice on alcohol: as easy as A...B...I?
AB  - Alcohol is widely consumed by the majority of the UK population and alcohol
      related harm is estimated to cost society L21 billion per year in healthcare,
      lost productivity costs, crime and antisocial behaviour. The dental setting
      offers an ideal opportunity to screen for harmful alcohol consumption; however,
      current emphasis is on the management of acute complications and risk associated
      in treating patients with excessive alcohol intake rather than screening and
      patient education. This article outlines ways in which dentists could improve
      their recognition of 'at risk' patients and then offer practical advice to help
      reduce the harmful effects of alcohol. 

PMID- 25571819
TI  - Summary of: is further intervention required to translate caries prevention and
      management recommendations into practice?
AB  - AIMS: In April 2010, the Scottish Dental Clinical Effectiveness Programme (SDCEP)
      published guidance on the Prevention and Management of Dental Caries in Children.
      The aims of this study were to determine if further intervention is required to
      translate the SDCEP guidance recommendations into practice and to identify
      salient beliefs associated with recommended practice. METHODS: Two postal surveys
      circulated to two independent random samples of dentists working in general
      dental practices in Scotland, before and after the publication of the guidance.
      The questionnaire items assessed current practice and beliefs relating to the
      prevention and management of dental caries in children. RESULTS: Response rates
      of 40% (n = 87) and 45% (n = 131) were achieved. The results highlight a gap
      between current practice and recommended practice. The majority of dentists do
      not 'always' perform recommended behaviours and many are following treatment
      strategies specifically not recommended in the guidance. More positive attitude,
      greater capability and motivation were significantly associated with performing
      more guidance recommended risk assessment and prevention behaviours. CONCLUSIONS:
      These findings highlight the need for further intervention to translate the SDCEP
      guidance recommendations into practice and give initial insight into the salient
      beliefs that may serve as targets for future interventions.

PMID- 25571820
TI  - Summary of: repair vs replacement of failed restorations in general dental
      practice: factors influencing treatment choices and outcomes.
AB  - OBJECTIVE: To investigate the impact of repair vs replacement of failed
      restorations on patient related outcome measures, and to explore the clinical
      factors that influence this decision. DESIGN: Multicentre, prospective practice
      based study.Setting Dental practices within Salford, Trafford and East Lancashire
      in the North West of England. SUBJECTS AND METHODS: General dental practitioners
      were asked to participate and to recruit adult patients attending for routine
      dental treatment.Interventions Repair or replacement of failed restorations. MAIN
      OUTCOME MEASURES: Dental anxiety before treatment using the Corah Dental Anxiety
      Scale and pain intensity immediately and 24 hours post-operatively using the
      McGill short form pain questionnaire. Operative outcomes included depth of
      caries, time taken to complete the procedure, use of local anaesthetic and dental
      material used. RESULTS: Of the 103 patients diagnosed with a failed restoration,
      a statistically significantly greater number underwent replacement than repair (p
      = 0.004). Patients undergoing repairs were significantly less anxious (p = 0.008)
      and had shorter procedure times (p = 0.044). Repairs were associated with minimal
      caries depth and less use of local anaesthetic. CONCLUSION: Failed restorations
      should be repaired where clinically possible, as they are quick and associated
      with less patient anxiety. Future research should focus on providing high quality
      prospective data evaluating the longevity of repaired vs replaced restorations.

PMID- 25571821
TI  - Reflections on a training course reorienting dental teams towards prevention.
AB  - Prevention is a core element of routine dental practice. However, members of the
      dental team often lack the required knowledge and skills to deliver effective
      evidence-based advice and support to patients. This paper describes the
      development and delivery of an innovative course designed to develop the
      preventive capacity of dental teams working in dental foundation training
      practices across London. The course contents were based upon national guidelines
      on evidence-based preventive care delivered in primary dental care settings
      (Delivering better oral health). An experienced team of trainers from diverse
      backgrounds successfully designed and delivered the courses and the initial
      feedback from participants indicate strong support for the approach developed. 

PMID- 25571822
TI  - Periodontitis: a potential risk factor for Alzheimer's disease.
AB  - The role of periodontitis as a risk factor for multiple systemic diseases is
      widely accepted and there is growing evidence of an association between
      periodontitis and sporadic late onset Alzheimer's disease (SLOAD). Recent
      epidemiologic, microbiologic and inflammatory findings strengthen this
      association, indicating that periodontal pathogens are possible contributors to
      neural inflammation and SLOAD. The aim of this article is to present contemporary
      evidence of this association. 

PMID- 25571840
TI  - Repair vs replacement of failed restorations in general dental practice: factors
      influencing treatment choices and outcomes.
AB  - OBJECTIVE: To investigate the impact of repair vs replacement of failed
      restorations on patient related outcome measures, and to explore the clinical
      factors that influence this decision. DESIGN: Multicentre, prospective practice
      based study. SETTING: Dental practices within Salford, Trafford and East
      Lancashire in the North West of England. SUBJECTS AND METHODS: General dental
      practitioners were asked to participate and to recruit adult patients attending
      for routine dental treatment. INTERVENTIONS: Repair or replacement of failed
      restorations. MAIN OUTCOME MEASURES: Dental anxiety before treatment using the
      Corah Dental Anxiety Scale and pain intensity immediately and 24 hours post
      operatively using the McGill short form pain questionnaire. Operative outcomes
      included depth of caries, time taken to complete the procedure, use of local
      anaesthetic and dental material used. RESULTS: Of the 103 patients diagnosed with
      a failed restoration, a statistically significantly greater number underwent
      replacement than repair (p = 0.004). Patients undergoing repairs were
      significantly less anxious (p = 0.008) and had shorter procedure times (p =
      0.044). Repairs were associated with minimal caries depth and less use of local
      anaesthetic. CONCLUSION: Failed restorations should be repaired where clinically
      possible, as they are quick and associated with less patient anxiety. Future
      research should focus on providing high quality prospective data evaluating the
      longevity of repaired vs replaced restorations.

PMID- 25571839
TI  - Is further intervention required to translate caries prevention and management
      recommendations into practice?
AB  - AIMS: In April 2010, the Scottish Dental Clinical Effectiveness Programme (SDCEP)
      published guidance on the Prevention and management of dental caries in children.
      The aims of this study were to determine if further intervention is required to
      translate the SDCEP guidance recommendations into practice and to identify
      salient beliefs associated with recommended practice. METHODS: Two postal surveys
      circulated to two independent random samples of dentists working in general
      dental practices in Scotland, before and after the publication of the guidance.
      The questionnaire items assessed current practice and beliefs relating to the
      prevention and management of dental caries in children. RESULTS: Response rates
      of 40% (n = 87) and 45% (n = 131) were achieved. The results highlight a gap
      between current practice and recommended practice. The majority of dentists do
      not 'always' perform recommended behaviours and many are following treatment
      strategies specifically not recommended in the guidance. More positive attitude,
      greater capability and motivation were significantly associated with performing
      more guidance recommended risk assessment and prevention behaviours. CONCLUSIONS:
      These findings highlight the need for further intervention to translate the SDCEP
      guidance recommendations into practice and give initial insight into the salient
      beliefs that may serve as targets for future interventions.

PMID- 25571841
TI  - Wnt inhibitory factor 1 (WIF1) is a marker of osteoblastic differentiation stage
      and is not silenced by DNA methylation in osteosarcoma.
AB  - Wnt pathway targeting is of high clinical interest for treating bone loss
      disorders such as osteoporosis. These therapies inhibit the action of negative
      regulators of osteoblastic Wnt signaling. The report that Wnt inhibitory factor 1
      (WIF1) was epigenetically silenced via promoter DNA methylation in osteosarcoma
      (OS) raised potential concerns for such treatment approaches. Here we confirm
      that Wif1 expression is frequently reduced in OS. However, we demonstrate that
      silencing is not driven by DNA methylation. Treatment of mouse and human OS cells
      showed that Wif1 expression was robustly induced by HDAC inhibition but not by
      methylation inhibition. Consistent with HDAC dependent silencing, the Wif1 locus
      in OS was characterized by low acetylation levels and a bivalent H3K4/H3K27
      trimethylation state. Wif1 expression marked late stages of normal osteoblast
      maturation and stratified OS tumors based on differentiation stage across
      species. Culture of OS cells under differentiation inductive conditions increased
      expression of Wif1. Together these results demonstrate that Wif1 is not targeted
      for silencing by DNA methylation in OS. Instead, the reduced expression of Wif1
      in OS cells is in context with their stage in differentiation. 

PMID- 25571842
TI  - Comparison between different bone treatments on areal bone mineral density (aBMD)
      and bone microarchitectural texture as assessed by the trabecular bone score
      (TBS).
AB  - PURPOSE: The objective of the study was to assess longitudinal effects of
      different osteoporosis treatments on TBS and aBMD at lumbar spine. METHOD: We
      analyzed 390 patients (men: 72; women: 318; age>40 years; mean follow-up of 20
      months and BMI<37 kg/m(2)). We stratified the cohort by treatments: Naive of
      treatment (Naive, n=67), Calcium and Vitamin D (CaVitD, n=87), Testosterone (Te,
      n=36), Alendronate (AL, n=88), Risedronate (Ri, n=39), Denosumab (Dmb, n=43) and
      Teriparatide (PTH, n=30). The follow-up changes from baseline were normalized at
      24 months. RESULTS: After 24 months, Naive group TBS decreased by 3.1% (p<0.05)
      whereas a non-significant increase was observed for spine aBMD (Delta=+0.5%).
      Compared to the Naive group, significant improvement (p<0.05) was observed in
      both TBS and aBMD for Te, AL, Ri, Dmb and PTH groups and in the CaVitD group for
      TBS. At the end of the follow-up, significant improvement have been observed for
      aBMD in Te (+4.4%), AL (+4.1%), Ri (+4.8), D (+8.8%) and PTH (+8.8%) groups.
      Significant improvement was observed only in the AL (+1.4%), Dmb (+2.8%) and PTH
      (+3.6%) groups for TBS. CONCLUSION: As expected, TBS of Naive subjects decreased
      with age. As expected a TBS preservation has been observed under AL and Ri. Te
      and CaVitD effects on TBS were evaluated for the first time: a similar
      preservation effect has been observed. A significant TBS increase was observed
      under Denosumab and PTH. TBS could be a useful tool to monitor treatment effects.

PMID- 25571843
TI  - Celastrol prevents circulatory failure via induction of heme oxygenase-1 and heat
      shock protein 70 in endotoxemic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Celastrol, a quinone methide extracted from the
      root of Tripterygium wilfordii Hook, possesses anti-oxidant and anti-inflammatory
      effects. Tripterygium wilfordii Hook is officially listed in the Chinese
      Pharmacopoeia and is used traditionally against rheumatoid arthritis, ankylosing
      spondylitis, and cancer. Furthermore, the circulatory protective effect of
      celastrol on an in vivo animal model of sepsis was investigated. AIM OF THE
      STUDY: Sepsis is a systemic inflammatory disorder that increases tissue oxidative
      stress and leads to multiple organ injury. We evaluated the beneficial effects of
      celastrol on multiple organ failure induced by lipopolysaccharide (LPS) in rats.
      MATERIALS AND METHODS: Celastrol (0.5 and 1.0 mg/kg, i.v.) was administered to
      anaesthetized rats 2 h before and 30 min after LPS challenge (10 mg/kg, i.v.).
      Eight hours later, cardiac and aortic protein expressions related to inflammatory
      responses, superoxide anion production, and reduced glutathione (GSH) level were
      measured. RESULTS: Treatment with celastrol prevented circulatory failure
      (bradycardia and hypotension) 8h after LPS challenge. The plasma levels of ALT,
      LDH, TNF-alpha, and nitric oxide metabolites increased markedly during sepsis,
      which significantly reduced after celastrol treatments. Celastrol attenuated
      iNOS, TNF-alpha, NF-kappaB phospho-p65 expression, superoxide anion production,
      and caspase 3 activity in the cardiovascular system, all of which were markedly
      elevated after LPS challenge. Furthermore, celastrol induced HO-1 and HSP70
      expressions increase in nuclear levels of Nrf2 and HSF-1, respectively, and
      increase cardiac GSH level 8h after LPS challenge. CONCLUSION: Anti-inflammatory
      and anti-oxidant effects of celastrol contribute to prevent circulatory failure
      in sepsis. Induction of HO-1 and HSP70 by celastrol participates in these
      beneficial effects.

PMID- 25571844
TI  - Anti-inflammatory effects of Crataeva nurvala Buch. Ham. are mediated via
      inactivation of ERK but not NF-kappaB.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Crataeva nurvala Buch. Ham. is an important
      medicinal plant in India, and its extracts and components were used to treat
      various inflammatory diseases, such as urinary tract infection, rheumatoid
      arthritis, and colitis. However, no systemic studies about anti-inflammatory
      effects of Crataeva nurvala Buch. Ham. and its underlying mechanisms of action
      have been reported. This study aimed to explore the anti-inflammatory effects of
      ethanol extracts of Crataeva nurvala Buch. Ham. (ECN). MATERIALS AND METHODS: The
      non-cytotoxic and maximal effective concentration of ECN was determined by
      measuring the formation of formazan from water-soluble tetrazolium salt in living
      cells. The inhibitory effect of ECN on nitric oxide (NO) synthesis was measured
      using Griess reagent, and Enzyme-linked immunosorbent assay (ELISA) was used to
      measure secreted tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 protein
      levels. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) and
      Western blotting analysis were used to assess the mRNA and protein expression of
      each inflammatory mediator or relating signaling protein, respectively. RESULTS:
      A non-cytotoxic concentration of ECN (<=200 MUg/ml) significantly reduced the
      production of NO and IL-6, but not TNF-alpha, in lipopolysaccharides (LPS)
      stimulated RAW 264.7 macrophages. Decreased production of NO by ECN was
      correlated with reduced expression of iNOS at the mRNA and protein levels.
      However, cyclooxygenase (COX)-2 expressions at mRNA and protein level were not
      regulated by ECN. The mRNA expression of IL-6 and IL-1beta, but not TNF-alpha,
      was also inhibited by ECN treatment in LPS-stimulated RAW 264.7 macrophages.
      Reduced production of inflammatory mediators by ECN was followed by decreased
      activity of mitogen-activated protein kinases (MAPKs), especially extracellular
      signal-regulated kinase (ERK), but not nuclear factor kappa-light-chain-enhancer
      of activated B cells (NF-kappaB). CONCLUSIONS: These results indicate that ECN
      inhibits LPS-induced inflammatory responses via negative regulation of ERK in
      murine macrophages, suggesting that ECN is a candidate for alleviating severe
      inflammation.

PMID- 25571845
TI  - Ethnomedicinal values, phenolic contents and antioxidant properties of wild
      culinary vegetables.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional medicines comprise a variety of
      health practices, approaches, knowledge, and beliefs. Documentation of
      traditional knowledge, estimation of total phenolics and antioxidant properties
      of plant species used as wild vegetables and in traditional medicines by the
      local communities of Lesser Himalayas-Pakistan are targeted. MATERIALS AND
      METHODS: Interviews, questionnaires, and focus group conversation with local
      informants were carried out to record ethno-medicinal values. Used value,
      percentage of people who have traditional knowledge, preference ranking and
      informant consensus factors were also measured. Standard analytical methods were
      applied to estimate phenolic contents and antioxidant properties in water and
      acetone extracts. RESULTS: A total of 39 plant species used as culinary
      vegetables and to treat 44 different health disorders are investigated.
      Significant levels of use value (0.571) and preference ranking (58% PPK, PR-5)
      are calculated for Ficus palmata, Ficus carica and Solanum nigrum. Elevated
      levels of total phenolics (144.5 mg GAE/100 g, FW), and flavonoid contents (142.5
      mgRtE/100 g, FW) were measured in the water extracts of Origanum vulgare, while
      Ficus palmata exhibits the highest flavonol contents (142.7 mg RtE/100 g, FW).
      Maximum DPPH activity is noted in the flowering buds of Bauhinia variegata
      (85.34%). However, highest values for OH(-) radical scavenging activity (75.12%),
      Fe(3+) reducing antioxidant power (54.50 uM GAE/100 g, FW), and total antioxidant
      capacity (180.8 uM AAE/100 g, FW) were measured in the water extracts of Origanum
      vulgare. CONCLUSION: Lesser Himalayas is a rich source of traditional cultural
      heritage, and plant biodiversity, which are under threat and necessitate urgent
      documentation. Present study is focused on the plant species used in traditional
      medicines and culinary vegetables as well. Preliminary determinations of
      phenoloic contents and antioxidant properties of various plant species were
      carried out. Present work will introduce new resource of medicinal and food
      plants, which could be used as functional food. Furthermore, phytochemical
      profiles, cellular based antioxidant properties, and isolation of active
      ingredients will be useful for consumers, and in the pharmaceutical and
      nutraceutical industries of the country.

PMID- 25571846
TI  - Lack of dose dependent kinetics of methyl salicylate-2-O-beta-D-lactoside in
      rhesus monkeys after oral administration.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Methyl salicylate-2-O-beta-d-lactoside (MSL) is
      one of the main active components isolated from Gaultheria yunnanensis, which is
      a traditional Chinese medicine used to treat arthritis and various aches and
      pains. Pharmacological researches showed that MSL had various effective
      activities in both in vivo and in vitro experiments. However, the
      pharmacokinetics features and oral bioavailability of MSL in primates were not
      studied up to now. AIM: To study the pharmacokinetics of different doses of MSL
      in rhesus monkeys and investigate the absolute bioavailability of MSL after oral
      administration. MATERIALS AND METHODS: Male and female rhesus monkeys were either
      orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous
      dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma
      were simultaneous measured by a simple, sensitive and reproducible high
      performance liquid chromatography method. RESULTS: Mean peak plasma concentration
      values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to
      171.83 MUg/mL after single-dose oral administration of MSL, and mean area under
      the concentration-time curve values ranged from 195.16 to 1107.76 MUg/mL h. Poor
      linearity of the kinetics of SA after oral administration of MSL was observed in
      the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot
      (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL
      was assessed to be 118.89 +/- 57.50, 213.54 +/- 58.98 and 168.72 +/- 76.58%,
      respectively. CONCLUSIONS: Bioavailability of MSL after oral administration in
      rhesus monkeys was measured for the first time. Pharmacokinetics parameters did
      not appear to be dose proportional among the three oral doses of treatments, and
      MSL showed an apparent absolute bioavailability in excess of 100% in rhesus
      monkeys based on the present study. In addition, a rapid, sensitive and reliable
      HPLC method was established and demonstrated for the research of traditional
      Chinese medicine in this study.

PMID- 25571847
TI  - Ethnozoological study of animals used by traditional healers in Silent Valley of
      Kerala, India.
AB  - AIM OF STUDY: India has great biodiversity of fauna. The use of fauna with
      medicinal properties is a common practice since pre-hispanic times. In the last
      decade, there has been an interest in ethnozoological studies in India.
      Ethnozoological studies are necessary in order to discover new medications for
      human health. There is urgency in recording such data. This is the first
      ethnozoological study in which statistical calculations about animals are done by
      the ICF method in Kerala, India. The purpose of this study is to analyze and
      record traditional knowledge of animals utilized by the indigenous people living
      on Silent Valley, located in Palakkad district of Kerala, India and to document
      the traditional names, preparation and uses of these animals. MATERIALS AND
      METHODS: Field study was carried out for a period of September 2011 to August
      2012 years in Kerala. The ethnomedicinal information was collected through
      interviews, informal meetings, open and group discussions and overt observations
      with semi-structured questionnaires among traditional healers. The collected data
      were analyzed through informant consensus factor (ICF) and fidelity level (FL).
      RESULTS: This study recorded a total of 57 families, 66 genera, and 69 species of
      animals that produced 163 methods for usages. Mammalian occupied 29% of the total
      animals listed, followed by aves (28%), insects (17%), reptiles (10%),
      actinopterygii (4%), malacostraca, amphibians and clitellata (each 3%), chilopoda
      (2%) and gastropoda (1%) of the whole, respectively. In regards to usage, 68
      species utilized as food products and medicinal uses, totaled 98.55% followed by
      one species for cosmetics (1.45%). CONCLUSION: This study indicated that the
      animals are still being used by the local healers of Palakkad district, to treat
      various illnesses. The empirical knowledge reported in this study will provide
      outstanding possibilities for the discovery of new sources of medicine for the
      drug industry.

PMID- 25571848
TI  - Immunomodulatory properties of Trehala manna decoction and its isolated
      carbohydrate macromolecules.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Trehala manna (Shekar tighal) is a cocoon-shaped
      manna produced by larval activity of Curculionidae family on some Echinops
      species. In Persian traditional medicine, it is used not only for the treatment
      of fever and constipation but also for sore throat, influenza and some other
      viral and bacterial infections which seems to be related to its boosting effects
      on immune system. The aim of this study was to evaluate immunomodulatory
      properties of Trehala manna and its isolated polysaccharides. MATERIALS AND
      METHODS: Several carbohydrate macromolecules were isolated from Trehala manna
      decoction using solvent-solvent extraction, ion exchange and size-exclusion
      chromatography. The macromolecules were characterized by gas chromatography-mass
      spectrometry and spectrophotometric methods. The immunomodulatory effects of
      Trehala manna decoction and its isolated polysaccharides were evaluated on Jurkat
      cells at different concentrations using WST-1 reagent. RESULTS: Seven water
      soluble polysaccharides were isolated with the structures of rhamnogalacturonan,
      glucogalacturonan, manno-arabinogalacturonan or homogalacturonan and the
      molecular weights (MW) of <=1.67-667 <= kDa. Large polysaccharides with MW >=667
      kDa and pectin inhibited the proliferation of Jurkat cells in a dose-dependent
      manner with the IC50 range of 98.06-429.53 ug/mL. The IC50 for low MW
      polysaccharides (around 1 kDa) did not show considerable cytotoxicity (IC50>1000
      ug/mL), in contrast, they exhibited a dose-dependent enhancement of cell
      proliferation at concentration range of 15.62-62.50 MUg/mL. CONCLUSION: Trehala
      aqueous decoction and its isolated polysaccharides showed some immunomodulatory
      effects on Jurkat cell line in a dose-dependent manner and the molecular weight
      of these polysaccharides also revealed a great impact on their
      cytotoxic/proliferative properties.

PMID- 25571849
TI  - An ethnobotanical study of medicinal plants used by ethnic people in Parbat
      district of western Nepal.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Nepal, a mountainous country having diversified
      topographic and climatic conditions, gives rise to a wide range of flora and
      fauna. In villages ethnic people, including Magar and Majhi highly depend on
      medicinal plants for their primary healthcare. Due to overexploitation,
      encroachment in forest for arable land and destruction of natural habitat,
      potentially useful medicinal plants are going to be threatened in their natural
      environment. There is a strong need to enlist highly valuable medicinal plants
      and use traditional knowledge to protect, utilize and manage them in ex-situ and
      in-situ conservation. The present research investigates and documents traditional
      knowledge on medicinal plants utilization as natural medicine by two ethnic
      communities Magar and Majhi of Parbat district in Western Nepal. METHODS:
      Ethnomedicinal data was collected during 2012-2013 by the following standard
      ethnobotanical methods. Data about medicinal uses of herbs, shrubs and trees were
      collected using semi-structured questionnaire, field observation, personal
      interview and group discussion with 334 (130 men and 204 women) pre-identified
      local informants, among which 13 male and 2 female were local healers.
      Statistical tool, informant consensus factors (F(IC)) and fidelity level (FL)
      values were used to analyze the importance of ethnomedicinal plants. RESULTS: A
      total of 132 ethnomedicinal plant species belonging to 99 genera and 67 families
      have been documented. These plants are used to treat various diseases and
      disorders grouped under 12 disease categories, with the highest number of species
      (61) being used for gastro-intestinal, parasitic and hepatobiliary disorders
      (FIC=0.78%), followed by blood and lymphatic system (F(IC)=0.76%) category. The
      highest fidelity level (FL) values recorded in Paris polyphylla (FL=96.0%)
      followed by Bergenia ciliata (FL=95.0%) confirms that these plants are the best
      plant species with medicinal properties. CONCLUSIONS: The two ethnic communities,
      Magar and Majhi, in Parbat district are rich in ethnomedicinal knowledge. The
      high degree of consensus among the informants suggests that current use and
      knowledge are still strong, and thus the preservation of indigenous knowledge
      would show good foresight in acting before much has been lost.

PMID- 25571850
TI  - From the RNA world to the RNA/protein world: contribution of some riboswitch
      binding species?
AB  - Some amino acids and their formal derivatives, currently riboswitch-binding
      species, could have interacted with polyribonucletides in prebiotic environments,
      leading to the peptide formation. If the resulting compounds had led to a
      sustainable polymerization of amino acids and the new structures had catalytic
      activity, such would have been an important contribution to the transition from
      the RNA world to the RNA/Protein world. 

PMID- 25571851
TI  - Clostridium difficile from food and surface samples in a Belgian nursing home: an
      unlikely source of contamination.
AB  - This study investigates the contamination of foods and surfaces with Clostridium
      difficile in a single nursing home. C. difficile PCR-ribotype 078 was found in
      one food sample and in none of the tested surfaces. These results indicate that
      food and surfaces are an unlikely source of C. difficile infection in this
      setting.

PMID- 25571852
TI  - Effect of Melilotus suaveolens extract on pulmonary microvascular permeability by
      downregulating vascular endothelial growth factor expression in rats with sepsis.
AB  - A typical indicator of sepsis is the development of progressive subcutaneous and
      body-cavity edema, which is caused by the breakdown of endothelial barrier
      function, leading to a marked increase in vascular permeability. Microvascular
      leakage predisposes to microvascular thrombosis, breakdown of microcirculatory
      flow and organ failure, which are common events preceding mortality in patients
      with severe sepsis. Melilotus suaveolens (M. suaveolens) is a Traditional Tibetan
      Medicine. Previous pharmacological studies have demonstrated that an ethanolic
      extract of M. suaveolens has powerful anti-inflammatory activity and leads to an
      improvement in capillary permeability. However, the mechanisms underlying its
      pharmacological activity remain elusive. The present study aimed to assess the
      impact of M. suaveolens extract tablets on pulmonary vascular permeability, and
      their effect on regulating lung inflammation and the expression of vascular
      endothelial growth factor (VEGF) in the lung tissue of rats with sepsis. A cecal
      ligation and puncture (CLP) sepsis model was established for both the control and
      treatment groups. ~2 h prior to surgery, 25 mg/kg of M. suaveolens extract tablet
      was administered to the treatment group. Polymerase chain reaction and western
      blot analyses were used to assess the expression of nuclear factor (NF)-kappaB
      and VEGF in the lung tissue, and ELISA was applied to detect changes in serum
      tumor necrosis factor-alpha as well as interleukins (IL) -1, -4, -6, and -10. The
      lung permeability, wet/dry weight ratio and lung pathology were determined. The
      results demonstrated that in the lung tissue of CLP-rats with sepsis, M.
      suaveolens extract inhibited the expression of NF-kappaB, reduced the
      inflammatory response and blocked the expression of VEGF, and thus significantly
      decreased lung microvascular permeability. The effects of M. Suaveolens extract
      may be of potential use in the treatment of CLP-mediated lung microvascular
      permeability.

PMID- 25571853
TI  - Celecoxib exerts antitumor effects in canine mammary tumor cells via COX-2
      independent mechanisms.
AB  - Celecoxib plays antitumor roles via multiple mechanisms in a variety of human
      cancers. The aim of this study was to clarify the mechanism of action of
      celecoxib in canine mammary tumors. We examined the antitumor effects of
      celecoxib in AZACB canine mammary tumor cells expressing low levels of
      cyclooxygenase-2 (COX-2) to minimize the effect of COX-2 on its activity. Our
      data revealed that celecoxib inhibited cell proliferation mainly via COX-2
      independent mechanisms. Specifically, celecoxib decreased the proportion of cells
      in S phase and increased G2/M arrest, which was associated with increased
      expression of the cyclin-dependent kinase inhibitors (CDKIs) p21 and p27. In
      addition, treatment with celecoxib downregulated COX-2 expression, and induced
      apoptosis via both the intrinsic and extrinsic pathways. These findings suggest
      that celecoxib might be a useful agent for the treatment of canine mammary
      tumors, regardless of COX-2 expression. In the future, it might be possible to
      use a combination of celecoxib and other antitumor agents to treat canine mammary
      tumors.

PMID- 25571854
TI  - B cell translocation gene 1 reduces the biological outcome of kidney cancer
      through induction of cell proliferation, cell cycle arrest, cell apoptosis and
      cell metastasis.
AB  - The aim of the present study was to determine the expression and function of B
      cell translocation gene 1 (BTG1) in kidney carcinoma. Kidney samples were
      obtained from cancer lesions (n=85) and the adjacent normal tissue (n=40) in
      kidney cancer patients immediately following endoscopic biopsy. The effect of
      BTG1 overexpression was examined in vitro utilizing a human kidney cancer cell
      line, ACHN, stably transfected with a recombinant lentivirus (LeBTG1 cells) and
      compared to empty vector-transfected controls (LeEmpty). BTG1 protein expression
      was significantly lower in kidney cancer tissue biopsies compared to normal
      tissue, as measured by immunohistochemistry (34.1 vs. 77.8% of tissues; P<0.05)
      and western blotting (0.481+/-0.051 vs. 0.857+/-0.081; P<0.05). In vitro analyses
      revealed that LeBTG1 cells had a reduced survival fraction compared to control
      LeEmpty cells, with higher rates of apoptosis (16.6+/-2.5 vs. 6.1+/-0.7%;
      P<0.05). The proportion of LeBTG1 cells in G(0)/G(1) stage and S phase was also
      significantly different from LeEmpty cells (66.8+/-5.3 and 22.2+/-1.5% vs. 44.4+/
      3.1 and 34.5+/-2.3%, respectively; P<0.05), and the migration and invasion of
      LeBTG1 cells was significantly impaired with respect to LeEmpty cells (74.0+/-9.0
      and 53.0+/-7.0 vs. 118.0+/-15.0 and 103.0+/-13.0, respectively; P<0.05). These
      effects were accompanied by decreased protein expression of cyclin D1, B-cell
      lymphoma 2 and matrix metalloproteinase 9 in LeBTG1 cells (0.118+/-0.018, 0.169+/
      0.015 and 0.207+/-0.027, respectively) compared to control LeEmpty cells (0.632+/
      0.061, 0.651+/-0.063 and 0.443+/-0.042, respectively; P<0.05). Reduced BTG1
      expression is associated with increased disease severity, suggesting it is a
      negative regulator of kidney cancer and can serve as a prognostic indicator. The
      results of the present study show that BTG1 protein levels were significantly
      reduced in kidney cancer biopsy specimens and were associated with disease
      progression and prognosis.

PMID- 25571856
TI  - Controllable organization and high throughput production of recoverable 3D tumors
      using pneumatic microfluidics.
AB  - Three-dimensional tumor culture methods offer a high degree of biological and
      clinical relevance to in vitro models as well as cancer therapy. However, a
      straightforward, dynamic, and high-throughput method for micro-manipulation of 3D
      tumors is not yet well established. In this study, we present a novel and simple
      strategy for producing biomimetic 3D tumors in a controllable, high throughput
      manner based on an integrated microfluidic system with well-established pneumatic
      microstructures. Serial manipulations, including one-step cell localization,
      array-like self-assembly, and real-time analysis of 3D tumors, are accomplished
      smoothly in the microfluidic device. The recovery of tumor products from the chip
      is performed by dynamic off-switch of the pneumatic microstructures. In addition,
      this microfluidic platform is demonstrated to be capable of producing multiple
      types of 3D tumors and performing the evaluation of tumor targeting by
      nanomedicine. The pneumatic microfluidic-based 3D tumor production shows
      potential for research on tumor biology, tissue engineering, and drug delivery. 

PMID- 25571855
TI  - Near-infrared imaging for the assessment of anastomotic patency, thrombosis, and
      reperfusion in microsurgery: a pilot study in a porcine model.
AB  - BACKGROUND: Advances in microsurgical techniques have increased the use of free
      tissue transfer. Methods of intraoperative flap perfusion assessment, however,
      still rely primarily on subjective evaluation of traditional clinical parameters.
      Anastomotic thrombosis, if not expeditiously identified and revised, can result
      in flap loss with significant associated morbidity. This study aims to evaluate
      the use of near-infrared (NIR) fluorescence imaging in the assessment of
      microsurgical anastomotic patency, thrombosis, and vascular revision. MATERIALS
      AND METHODS: A model of pedicle thrombosis was created using bilateral abdominal
      flaps isolated on deep superior epigastric vascular pedicles in four Yorkshire
      pigs. Following flap elevation, microvascular arterial and venous anastomoses
      were performed unilaterally, preserving an intact contralateral control flap.
      Thrombosis was induced at the arterial anastomosis site using ferric chloride,
      and both flaps imaged using NIR fluorescence angiography. The thrombosed vascular
      segments were subsequently excised and new anastomoses performed to restore flow.
      Follow-up imaging of both flaps was then obtained to confirm patency using
      fluorescence imaging technology. RESULTS: Pedicled abdominal flaps were created
      and successful anastomotic thrombosis was induced unilaterally in each pig.
      Fluorescence imaging technology identified large decreases in tissue perfusion of
      the thrombosed flap within 2 minutes. After successful revision anastomosis, NIR
      imaging demonstrated dramatic increase in flow to the reconstructed flap, but
      intensity did not return to pre-thrombosis levels. CONCLUSIONS: Early
      identification of anastomotic thrombosis is important in successful free tissue
      transfer. Real-time, intraoperative evaluation of flap perfusion, anastomotic
      thrombosis, and successful revision can be performed using NIR fluorescence
      imaging.

PMID- 25571859
TI  - On the role of the surface oxygen species during A-H (A = C, N, O) bond
      activation: a density functional theory study.
AB  - During A-H (A = C, N, O) bond cleavage on O* or OH* pre-covered (111) surfaces,
      the oxygen species play the role of modifying the reaction energy by changing the
      species involved in the initial and final states of the reaction. 

PMID- 25571858
TI  - Fabrication of highly stable glyco-gold nanoparticles and development of a glyco
      gold nanoparticle-based oriented immobilized antibody microarray for lectin
      (GOAL) assay.
AB  - The design of high-affinity lectin ligands is critical for enhancing the
      inherently weak binding affinities of monomeric carbohydrates to their binding
      proteins. Glyco-gold nanoparticles (glyco-AuNPs) are promising multivalent glycan
      displays that can confer significantly improved functional affinity of glyco
      AuNPs to proteins. Here, AuNPs are functionalized with several different
      carbohydrates to profile lectin affinities. We demonstrate that AuNPs
      functionalized with mixed thiolated ligands comprising glycan (70 mol %) and an
      amphiphilic linker (30 mol %) provide long-term stability in solutions containing
      high concentrations of salts and proteins, with no evidence of nonspecific
      protein adsorption. These highly stable glyco-AuNPs enable the detection of model
      plant lectins such as Concanavalin A, wheat germ agglutinin, and Ricinus communis
      Agglutinin 120, at subnanomolar and low picomolar levels through UV/Vis
      spectrophotometry and dynamic light scattering, respectively. Moreover, we
      develop in situ glyco-AuNPs-based agglutination on an oriented immobilized
      antibody microarray, which permits highly sensitive lectin sensing with the naked
      eye. In addition, this microarray is capable of detecting lectins presented
      individually, in other environmental settings, or in a mixture of samples. These
      results indicate that glyconanoparticles represent a versatile and highly
      sensitive method for detecting and probing the binding of glycan to proteins,
      with significant implications for the construction of a variety of platforms for
      the development of glyconanoparticle-based biosensors. 

PMID- 25571857
TI  - Improved identification and enrolment into care of HIV-exposed and -infected
      infants and children following a community health worker intervention in
      Lilongwe, Malawi.
AB  - BACKGROUND: Early identification and entry into care is critical to reducing
      morbidity and mortality in children with HIV. The objective of this report is to
      describe the impact of the Tingathe programme, which utilizes community health
      workers (CHWs) to improve identification and enrolment into care of HIV-exposed
      and -infected infants and children. METHODS: Three programme phases are
      described. During the first phase, Mentorship Only (MO) (March 2007-February
      2008) on-site clinical mentorship on paediatric HIV care was provided. In the
      second phase, Tingathe-Basic (March 2008-February 2009), CHWs provided HIV
      testing and counselling to improve case finding of HIV-exposed and -infected
      children. In the final phase, Tingathe-PMTCT (prevention of mother-to-child
      transmission) (March 2009-February 2011), CHWs were also assigned to HIV-positive
      pregnant women to improve mother-infant retention in care. We reviewed routinely
      collected programme data from HIV testing registers, patient mastercards and
      clinic attendance registers from March 2005 to March 2011. RESULTS: During MO, 42
      children (38 HIV-infected and 4 HIV-exposed) were active in care. During Tingathe
      Basic, 238 HIV-infected children (HIC) were newly enrolled, a six-fold increase
      in rate of enrolment from 3.2 to 19.8 per month. The number of HIV-exposed
      infants (HEI) increased from 4 to 118. During Tingathe-PMTCT, 526 HIC were newly
      enrolled over 24 months, at a rate of 21.9 patients per month. There was also a
      seven-fold increase in the average number of exposed infants enrolled per month
      (9.5-70 patients per month), resulting in 1667 enrolled with a younger median age
      at enrolment (5.2 vs. 2.5 months; p < 0.001). During the Tingathe-Basic and
      Tingathe-PMTCT periods, CHWs conducted 44,388 rapid HIV tests, 7658 (17.3%) in
      children aged 18 months to 15 years; 351 (4.6%) tested HIV-positive. Over this
      time, 1781 HEI were enrolled, with 102 (5.7%) found HIV-infected by positive PCR.
      Additional HIC entered care through various mechanisms (including positive
      linkage by CHWs and transfer-ins) such that by February 2011, a total of 866 HIC
      were receiving care, a 23-fold increase from 2008. CONCLUSIONS: A multipronged
      approach utilizing CHWs to conduct HIV testing, link HIC into care and provide
      support to PMTCT mothers can dramatically improve the identification and
      enrolment into care of HIV-exposed and -infected children.

PMID- 25571860
TI  - Multi-pathway assessment of human health risk posed by polycyclic aromatic
      hydrocarbons.
AB  - To assess aggregate exposure to polycyclic aromatic hydrocarbons (PAHs) via
      several environmental media and pathways, a probabilistic framework for multi
      pathway health risk assessment that integrates PAHs potency equivalence factors,
      risk estimation modeling, and Monte Carlo simulation was applied to a case study
      in Nanjing, which is an important industrial city in China. Incremental lifetime
      risk of additional cancers posed by exposure to 16 USEPA priority PAHs in air,
      water, soil, and fish was assessed. Risks to three age groups, infants, children,
      and adults, through various exposure pathways, including oral ingestion, dermal
      absorption, and inhalation, were estimated. Results of the analysis of risk
      indicated that B[a]P, B[b]F, and BA were the predominant PAHs pollutants in
      Nanjing. Risk of additional cancer for local adults was on average 2.62 * 10(-5).
      The risks were primarily due to ingestion of fish and inhalation, which
      contributed 99 % of the total risks. By contrast, risk to infants was essentially
      negligible. Results of a sensitivity analysis indicated that the input variables
      of concentration of PAHs in fish (C f), the body weight (BW), and the ingestion
      rate of fish (IRf) were the major influences on estimates of risks. 

PMID- 25571861
TI  - Elucidation of the concise biosynthetic pathway of the communesin indole
      alkaloids.
AB  - The communesins are a prominent class of indole alkaloids isolated from
      Penicillium species. Owing to their daunting structural framework and potential
      as pharmaceuticals, communesins have inspired numerous synthetic studies.
      However, the genetic and biochemical basis of communesin biosynthesis has
      remained unexplored. Herein, we report the identification and characterization of
      the communesin (cns) biosynthetic gene cluster from Penicillium expansum. We
      confirmed that communesin is biosynthesized by the coupling of tryptamine and
      aurantioclavine, two building blocks derived from L-tryptophan. The
      postmodification steps were mapped by targeted-gene-deletion experiments and the
      structural elucidation of intermediates and new analogues. Our studies set the
      stage for the biochemical characterization of communesin biosynthesis. This
      knowledge will aid our understanding of how nature generates remarkable
      structural complexity from simple precursors. 

PMID- 25571862
TI  - Different behaviour of molecules in dark SERS state on colloidal Ag nanoparticles
      estimated by truncated power law analysis of blinking SERS.
AB  - For single colloidal Ag nanoaggregates, covered with either large or small
      amounts of citrate anions, blinking surface-enhanced Raman scattering (SERS) of
      anionic thiacyanine was measured and analyzed by a truncated power law. The power
      law without and with an exponential function reproduces a probability
      distribution for bright and dark SERS events versus their duration times,
      respectively. On the Ag surface, except for junctions of the nanoaggregate with a
      large or small amount of the citrate anions, two-dimensional fast or one
      dimensional slow random walk of the anionic thiacyanine, respectively, was
      estimated by the exponents and the truncation times in the power law for the dark
      SERS events. In addition, the power law exponents for the bright SERS events were
      derived to be of similar values, indicating a similar molecular random walk near
      the junction, which may be dominated evenly by a surface-plasmon-enhanced
      electromagnetic field on the same-sized Ag nanoaggregate. Thus, not only the
      bright SERS, but also the dark SERS molecular behaviour on the Ag surface was
      investigated by the truncated power law analysis. 

PMID- 25571863
TI  - The influence of the modifiable life-style factors body mass index and smoking on
      the outcome of mid-urethral sling procedures for female urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this observational study was to
      investigate the influence of body mass index (BMI) smoking and age on the cure
      rate, rate of complications and patient satisfaction with mid-urethral sling
      (MUS) procedures. METHODS: Pre-, peri- and postoperative (8 weeks and 1 year)
      data were retrieved from the Swedish National Register for Gynecological Surgery
      of MUS procedures (retropubic procedures, n = 4,539; transobturator procedures, n
      =1,769) performed between January 2006 and December 2011. Multiple logistic
      regression analyses were performed between the outcome variables and BMI and
      smoking, presented as adjusted odds ratios (adjOR) with 95 % confidence interval
      (CI). RESULTS: Subjective 1-year cure rate was 87.4 % for all MUS procedures
      (88.3 % with the retropubic technique and 85.2 % with the transobturator
      technique (p = 0.002). Preoperative daily urinary leakage and urgency were more
      common with increasing BMI, but surgery reduced symptoms in all BMI groups. Lower
      cure rate was seen in women with a BMI >30 (0.49; CI 0.33-0.73), in diabetics
      (0.50; CI 0.35-0.74) and women aged > 80 years (0.18; CI 0.06-0.51).
      Perioperative complications were more common in the retropubic group (4.7 % vs
      2.3 % in the transobturator group, p=0.001) and in women with BMI < 25. Smoking
      did not influence any of the outcome variables. CONCLUSIONS: The overall 1-year
      cure rate for MUS procedures was 87 %, but was negatively influenced by BMI >30,
      diabetes and age > 80 years. Perioperative complications were more common with
      the retropubic procedure than with the transobturator technique, and in women
      with a BMI < 25. Smoking did not impact on any of the studied outcome variables.

PMID- 25571864
TI  - Effect of increasing awareness of pelvic floor muscle function on pelvic floor
      dysfunction: a randomized controlled trial.
AB  - INTRODUCTION AND HYPOTHESIS: This randomized controlled study with blinding
      allocation evaluated pelvic floor knowledge (PFK) and the presence of pelvic
      floor dysfunction (PFD) in women office workers. The effects of receiving pelvic
      floor muscle (PFM) health education on PFK and PFD were also evaluated. METHODS:
      Of 161 female volunteers, 145 (90.0 %, age range 18-69 years) responded. They
      were randomly allocated to three groups (group A 48, group B 48, group C 49).
      Online surveys were completed by all groups on three occasions using validated
      tools (Prolapse and Incontinence Knowledge Quiz, PFDI-20, PFIQ-7) and PFM
      exercise items. On completion of the baseline survey, groups A and B received an
      education intervention (group C was the control). Following this, all
      participants completed the second survey. Two months later, to allow time for the
      PFM exercises to have an effect, group A attended a re-education presentation,
      followed by the final survey administered to all groups. The results were
      analyzed using analysis of variance and Tukey's test. RESULTS: Participants
      receiving both PFM exercise education interventions (group A) and those receiving
      only the first education intervention (group B) showed highly significant
      improvements in PFK compared with the control group (both p < 0.001). The groups
      receiving PFM exercise education also showed a highly significant decrease in PFD
      symptoms (p < 0.001), and a significant increase in quality of life (QoL; p <
      0.05). CONCLUSIONS: While the results of this study cannot be generalized to all
      women, low levels of PFK was associated with high a prevalence of PFD, and an
      increase in knowledge/awareness following education was significantly associated
      with an increase in QoL and a decrease in PFD symptoms.

PMID- 25571865
TI  - First evidence of neosaxitoxin as a long-acting pain blocker in bladder pain
      syndrome.
AB  - INTRODUCTION AND HYPOTHESIS: Neosaxitoxin is a phycotoxin whose molecular
      mechanism of action shows a reversible inhibition of voltage-gated sodium
      channels at the axonal level, impeding nerve impulse propagation. This study was
      designed to evaluate the clinical efficacy of neosaxitoxin as a long-acting pain
      blocker in the treatment of bladder pain syndrome (BPS). METHODS: Five patients
      with a diagnosis of BPS received a total dose of 80 ug of neosaxitoxin in an
      isoosmotic solution of 0.9 % NaCl, pH 6.5. Infiltration was performed via
      cystoscopy under spinal anesthesia. Questionnaires were administered immediately
      before and 7, 30 and 90 days after the procedure to measure the patients'
      reported pain severity and quality of life. RESULTS: This study, for the first
      time, showed the effect of blocking the neuronal transmission of pain by local
      infiltration of neosaxitoxin into the bladder submucosa. All five patients
      successfully responded to the treatment. Furthermore, the analgesic effect lasted
      for the entire 90 days of follow-up without the need for a second infiltration,
      and no adverse reactions to neosaxitoxin were detected. CONCLUSIONS: Neosaxitoxin
      infiltration was shown to be a safe and effective intervention to control pain
      related to BPS. It was well tolerated by patients, who experienced extended pain
      relief and associated beneficial effects over a follow-up of 90 days. These
      results confirm the effectiveness of neosaxitoxin as a long-acting local pain
      blocker.

PMID- 25571867
TI  - Sphere to rod transitions in self assembled systems probed using direct force
      measurement.
AB  - The influence of nanoparticle shape, in particular the sphere to rod transition,
      on surface forces and consequently the properties of colloidal fluids is an
      interesting but not well investigated phenomenon. Here, the surface force
      behaviour of concentrated surfactant solutions containing cetyltrimethylammonium
      bromide and sodium salicylate with micelle shapes varying from slightly prolate
      to high aspect ratio rods was measured. Atomic force microscopy (AFM) with both
      rigid particle and soft droplet probes was used with comparisons and analysis
      made using the Chan-Dagastine-White model. It is observed that small changes to
      the micelle shape result in no discernable differences to the surface force
      behaviour, however, once the micelles are elongated significantly, the long range
      forces adjust in nature from oscillatory to that of a single attractive force
      well. This highlights the importance that nanocolloid shape has on the behaviour
      and properties of emulsions and other colloidal fluids, specifically for emulsion
      flocculation and handling in systems of rod and worm like micelles. 

PMID- 25571866
TI  - Neurite outgrowth resistance to rho kinase inhibitors in PC12 Adh cell.
AB  - Rho kinase (ROCK) inhibitor is a promising agent for neural injury disorders,
      which mechanism is associated with neurite outgrowth. However, neurite outgrowth
      resistance occurred when PC12 Adh cell was treated with ROCK inhibitors for a
      longer time. PC12 Adh cells were treated with ROCK inhibitor Y27632 or NGF for
      different durations. Neurite outgrowth resistance occurred when PC12 Adh cell
      exposed to Y27632 (33 uM) for 3 or more days, but not happen when exposed to
      nerve growth factor (NGF, 100 ng/mL). The gene expression in the PC12 Adh cells
      treated with Y27632 (33 uM) or NGF (100 ng/mL) for 2 or 4 days was assayed by
      gene microarray, and the reliability of the results were confirmed by real-time
      RT-PCR. Cluster analysis proved that the gene expression profile of PC12 Adh cell
      treated with Y27632 for 4 days was different from that treated with Y27632 for 2
      days and those treated with NGF for 2 and 4 days, respectively. Pathway analysis
      hinted that the neurite outgrowth resistance could be associated with up
      regulation of inflammatory pathways, especially rno04610 (complement and
      coagulation cascades), and down-regulation of cell cycle pathways, especially
      rno04110. 

PMID- 25571869
TI  - Thermal conduction in single-layer black phosphorus: highly anisotropic?
AB  - The single-layer black phosphorus is characteristic for its puckered structure,
      which has led to distinct anisotropy in its optical, electronic, and mechanical
      properties. We use the non-equilibrium Green's function approach and the first
      principles method to investigate the thermal conductance for single-layer black
      phosphorus in the ballistic transport regime, in which the phonon-phonon
      scattering is neglected. We find that the anisotropy in the thermal conduction is
      very weak for the single-layer black phosphorus--the difference between two in
      plane directions is less than 4%. Our phonon calculations disclose that the out
      of-plane acoustic phonon branch has lower group velocities in the direction
      perpendicular to the pucker, as the black phosphorus is softer in this direction,
      leading to a weakening effect for the thermal conductance in the perpendicular
      direction. However, the longitudinal acoustic phonon branch behaves abnormally;
      i.e., the group velocity of this phonon branch is higher in the perpendicular
      direction, although the single-layer black phosphorus is softer in this
      direction. The abnormal behavior of the longitudinal acoustic phonon branch is
      closely related to the highly anisotropic Poisson's ratio in the single-layer
      black phosphorus. As a result of the counteraction between the out-of-plane
      phonon mode and the in-plane phonon modes, the thermal conductance in the
      perpendicular direction is weaker than the parallel direction, but the anisotropy
      is pretty small.

PMID- 25571868
TI  - Association between interleukin-1beta and tumor necrosis factor-alpha
      polymorphisms and symptoms of dyspepsia.
AB  - Interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha have significant
      roles in the mediation of inflammatory immune responses and are also potent
      inhibitors of gastric acid secretion in the stomach. The present study aimed to
      investigate the associations between polymorphisms at position -31 (T>C) of the
      IL-1beta gene and -857 (C>T) of the TNF-alpha gene with dyspeptic symptoms.
      Polymorphisms at position -31 (T>C) of the IL-1beta gene and -857 (C>T) of the
      TNF-alpha gene were genotyped in 261 subjects, including 126 subjects without
      symptoms and 135 subjects exhibiting symptoms of dyspepsia. The IL-1beta -31 CC
      genotype was inversely associated with dyspeptic symptoms in all subjects, as
      determined by the Fisher's exact test [odds ratio (OR), 0.57; 95% confidence
      interval (CI), 0.34-0.96; P=0.046]; however, this association was not detected
      following logistic regression analysis. Within the subgroups of symptoms, the CC
      genotype was also inversely associated with upper abdominal pain (OR, 0.28; 95%
      CI, 0.12-0.67; P=0.003) and epigastric pain syndrome (EPS)-like symptoms (OR,
      0.14; 95% CI, 0.07-0.28; P=0.003), according to the Rome III classifications.
      These associations were also found following logistic regression analysis (upper
      abdominal pain: OR, 0.34; 95% CI, 0.14-0.80; P=0.014; and EPS-like symptoms: OR,
      0.41; 95% CI, 0.20-0.84; P=0.015). No significant associations were identified
      between the TNF-alpha -857 polymorphism and dyspeptic symptoms, including amongst
      the various subtypes analyzed. In conclusion, the IL-1beta -31 CC genotype was
      inversely associated with susceptibility to dyspeptic symptoms, in particular,
      upper abdominal pain and EPS-like symptoms.

PMID- 25571870
TI  - RNAi-mediated knockdown of the c-jun gene sensitizes radioresistant human
      nasopharyngeal carcinoma cell line CNE-2R to radiation.
AB  - This study aimed to investigate the effect of RNA interference (RNAi)-mediated
      downregulation of the expression of the c-jun gene (a proto-oncogene) on the
      radiosensitivity of a radioresistant human nasopharyngeal carcinoma cell line
      (CNE-2R) and to validate its potential as an anticancer target. A lentiviral
      vector with c-jun small hairpin RNA (shRNA) was constructed and transfected into
      CNE-2R cells. The gene silencing efficiency of these recombinants was confirmed
      by RT-PCR and western blotting. Radiosensitivity, cell proliferation, cell cycle
      profile and apoptosis were assessed using colony formation assay, CCK-8 assay and
      flow cytometry, respectively. The lentiviral shRNA efficiently knocked down the
      expression of c-jun at both the mRNA and protein levels (P<0.05). c-jun
      downregulated CNE-2R cells exhibited significantly decreased cell proliferation
      and enhanced radiosensitivity compared to the control group (P<0.05), and the
      effects were likely due to G2/M phase arrest and enhanced cell apoptosis. These
      data provide evidence that c-jun may be involved in the radioresistance of
      nasopharyngeal carcinoma (NPC) and knockdown of the c-jun gene may be a potential
      strategy to enhance the radiation sensitivity of NPC.

PMID- 25571871
TI  - Evaluation of the current prostate cancer staging system based on cancer-specific
      mortality in the surveillance, epidemiology, and end results database.
AB  - BACKGROUND: Prostate cancer is the most common noncutaneous malignancy diagnosed
      in men. From a large population-based database, this study aimed to report
      prostate cancer-specific mortality (PCSM) rates of men diagnosed with various
      presentations of prostate cancer and to examine the adequacy of the current
      American Joint Committee on Cancer (AJCC) staging system. PATIENTS AND METHODS:
      The Surveillance, Epidemiology, and End Results (SEER) database was queried for
      all patients diagnosed with prostate cancer from 1997 to 2005. PCSM was reported
      by the classification of extent of disease provided by the SEER database, for
      clinically staged and pathologically staged cohorts. RESULTS: Using the
      cumulative incidence method, PCSM at 10 years for all patients (n = 354,326) was
      5% for clinically localized (CL) lesions, 7% for T3aN0M0, 14% for T3bN0M0, 26%
      for T4N0M0, 27% for TanyN1M0, and 66% for TanyNanyM1. Within the pathologically
      staged subgroup (n = 108,135), PCSM at 10 years was 1% for CL lesions, 4% for
      T3aN0M0, 9% for T3bN0M0, 9% for T4N0M0, and 19% for TanyN1M0. CONCLUSION: Staging
      of any disease site aims to accurately communicate, prognosticate, and guide
      management for that particular level of disease. Stage IV prostate cancer is a
      diverse group, with PCSM in the subgroups ranging from 9% to 68% in this study.
      Considering the favorable outcomes of those with T4 or N1 nonmetastatic prostate
      cancer relative to those with M1 disease, the authors propose that T4 or N1 M0
      prostate cancer should be reclassified into a new stage IIIB and that patients
      with such disease should be offered curative-intent therapy whenever possible.

PMID- 25571872
TI  - Percutaneous closure of a hemodynamically significant connection between the
      inferior vena cava and the left atrium.
AB  - OBJECTIVE AND BACKGROUND: A connection between the inferior vena cava (IVC) and
      the left atrium (LA) can occur as a rare complication after surgical atrial
      septum defect (ASD) repair. We demonstrate the first case of a percutaneous
      closure of this connection. METHODS AND RESULTS: A 67-year-old female was
      admitted to hospital due to exertional dyspnea. A history of a surgical ASD
      repair in 1960 and 1966 with a residual shunt was already known. Transesophageal
      echocardiography and a CT scan revealed a hemodynamically significant drainage of
      the IVC into the LA. This connection was successfully closed percutaneously with
      an AMPLATEZR Duct Occluder I (St. Jude Medical, St. Paul, MN). Post-procedural CT
      scan and transthoracic echocardiography demonstrated a stable position and there
      was also no evidence of a residual shunt. The patient reported a significant
      reduction of exertional dyspnea. CONCLUSION: Percutaneous closure of an IVC to LA
      connection in this case was safe and feasible. The decision about which device is
      optimal must be made on an individual basis.

PMID- 25571873
TI  - Multitasking in a plant-ant interaction: how does Acacia myrtifolia manage both
      ants and pollinators?
AB  - Plant associations with protective ants are widespread among angiosperms, but
      carry the risk that ants will deter pollinators as well as herbivores. Such
      conflict, and adaptations to ameliorate or prevent the conflict, have been
      documented in African and neotropical acacias. Ant-acacia associations occur in
      Australia, but little is known of their ecology. Moreover, recent phylogenetic
      evidence indicates that Australian acacias are only distantly related to African
      and American acacias, providing an intercontinental natural experiment in the
      management of ant-pollinator conflict. We examined four populations of Acacia
      myrtifolia over a 400-km environmental gradient in southeastern Australia using
      ant and pollinator exclusion as well as direct observation of ants and
      pollinators to assess the potential for ant-pollinator conflict to affect seed
      set. Native bees were the only group of floral visitors whose visitation rates
      were a significant predictor of fruiting success, although beetles and wasps may
      play an important role as "insurance" pollinators. We found no increase in
      pollinator visitation or fruiting success following ant exclusion, even with
      large sample sizes and effective exclusion. Because ants are facultative visitors
      to A. myrtifolia plants, their presence may be insufficient to interfere greatly
      with floral visitors. It is also likely that the morphological location of
      extrafloral nectaries tends to draw ants away from reproductive parts, although
      we commonly observed ants on inflorescences, so the spatial separation is not
      strict. A. myrtifolia appears to maintain a generalized mutualism over a wide
      geographic range without the need for elaborate adaptations to resolve ant
      pollinator conflict. 

PMID- 25571874
TI  - Aberrant NMDA receptor DNA methylation detected by epigenome-wide analysis of
      hippocampus and prefrontal cortex in major depression.
AB  - Current perspectives on the molecular underpinnings of major depressive disorder
      (MDD) posit a mechanistic role of epigenetic DNA modifications in mediating the
      interaction between environmental risk factors and a genetic predisposition.
      However, conclusive evidence for differential methylation signatures in the
      brain's epigenome of MDD patients as compared to controls is still lacking. To
      address this issue, we conducted a pilot study including an epigenome-wide
      methylation analysis in six individuals diagnosed with recurrent MDD and six
      control subjects matched for age and gender, with a priori focus on the
      hippocampus and prefrontal cortex as pathophysiologically relevant candidate
      regions. Our analysis revealed differential methylation profiles of 11 genes in
      hippocampus and 20 genes in prefrontal cortex, five of which were selected for
      replication of the methylation status using pyrosequencing. Among these
      replicated targets, GRIN2A was found to be hypermethylated in both prefrontal
      cortex and hippocampus. This finding may be of particular functional relevance as
      GRIN2A encodes the glutamatergic N-methyl-D-aspartate receptor subunit epsilon-1
      (NR2A) and is known to be involved in a plethora of synaptic plasticity-related
      regulatory processes probably disturbed in MDD. 

PMID- 25571875
TI  - Regulation of the voltage gated K channel Kv1.3 by recombinant human klotho
      protein.
AB  - BACKGROUND/AIMS: Klotho, a protein mainly produced in the kidney and released
      into circulating blood, contributes to the negative regulation of 1,25(OH)2D3
      formation and is thus a powerful regulator of mineral metabolism. As beta
      glucuronidase, alpha Klotho protein further regulates the stability of several
      carriers and channels in the plasma membrane and thus regulates channel and
      transporter activity. Accordingly, alpha Klotho protein participates in the
      regulation of diverse functions seemingly unrelated to mineral metabolism
      including lymphocyte function. The present study explored the impact of alpha
      Klotho protein on the voltage gated K+ channel Kv1.3. METHODS: cRNA encoding
      Kv1.3 (KCNA3) was injected into Xenopus oocytes and depolarization induced
      outward current in Kv1.3 expressing Xenopus oocytes determined utilizing dual
      electrode voltage clamp. Experiments were performed without or with prior
      treatment with recombinant human Klotho protein (50 ng/ml, 24 hours) in the
      absence or presence of a beta-glucuronidase inhibitor D-saccharic acid-1,4
      lactone (DSAL, 10 uM). Moreover, the voltage gated K+ current was determined in
      Jcam lymphoma cells by whole cell patch clamp following 24 hours incubation
      without or with recombinant human Klotho protein (50 ng/ml, 24 hours). Kv1.3
      protein abundance in Jcam cells was determined utilising fluorescent antibodies
      in flow cytometry. RESULTS: In Kv1.3 expressing Xenopus oocytes the Kv1.3
      currents and the protein abundance of Kv1.3 were both significantly enhanced
      after treatment with recombinant human Klotho protein (50 ng/ml, 24 hours), an
      effect reversed by presence of DSAL. Moreover, treatment with recombinant human
      Klotho protein increased Kv currents and Kv1.3 protein abundance in Jcam cells.
      CONCLUSION: Alpha Klotho protein enhances Kv1.3 channel abundance and Kv1.3
      currents in the plasma membrane, an effect depending on its beta-glucuronidase
      activity.

PMID- 25571876
TI  - Blood pressure and intracranial aneurysms in autosomal dominant polycystic kidney
      disease.
AB  - BACKGROUND/AIMS: Autosomal dominant polycystic kidney disease (ADPKD) is
      correlated with an increased frequency of both intracranial aneurysms (ICANs),
      and arterial hypertension (AH). The aim of our study was to search for the
      association between blood pressure (BP) and ICANs in ADPKD patients. METHODS:
      Sixty-eight adult, pre-dialysis phase ADPKD patients underwent both screening for
      ICANs with magnetic resonance angiography of the brain, and ambulatory blood
      pressure monitoring (ABPM). RESULTS: ICANs were diagnosed in 10 patients (ICAN+
      group), while in 58 were not (ICAN- group). The nighttime maximum diastolic blood
      pressure (DBP), maximum increase in DBP from measurement to measurement (positive
      delta of DBP) at night, and the standard deviation of the daytime mean arterial
      pressure were significantly higher in ICAN+ compared to ICAN- patients.
      Additionally, in a subgroup of patients after 45 years-of-age, ICAN+ patients had
      significantly higher maximum 24-hour and daytime systolic blood pressure, maximum
      24-hour, daytime, nighttime DBP, maximum daytime and nighttime positive delta of
      DBP compared to ICAN- cases. CONCLUSIONS: Development of ICANs in hypertensive
      ADPKD patients is accompanied with higher values of some BP parameters measured
      by ABPM. Hypertensive ADPKD patients with substantial fluctuations in BP assessed
      by ABPM, especially those after 45 years-of-age, should become candidates for
      screening for ICANs.

PMID- 25571877
TI  - Superior predictive value for NTproBNP compared with high sensitivity cTnT in
      dialysis patients: a pilot prospective observational study.
AB  - BACKGROUND/AIMS: The clinical utility of the new biomarker, high sensitivity
      cardiac T troponin (hs-cTnT) is still unclear in dialysis patients. Furthermore,
      the prognostic value of combining N-terminal pro-B-type natriuretic peptide (NT
      pro-BNP) and hs-cTnT has not been explored so far. The objective of this pilot
      study was to determine the utility of hs-cTnT alone versus hs-cTnT in combination
      with NT-proBNP for predicting death in a stable hemodialysis cohort. METHODS: A
      prospective observational pilot study including 98 chronic asymptomatic
      hemodialysis patients with a follow up period of 24 months was designed. The cut
      off values for NT-proBNP and hs-cTnT were calculated using receiver operating
      characteristic (ROC) analysis, using mortality as an end-point. Based on the cut
      off values, the cohort was divided into four groups. Group 1--NT-proBNP < 14275
      pg/ml and hs-cTnT < 69.48 ng/l; group 2--NT-proBNP < 14275 pg/ml and hs-cTnT >
      69.48 ng/l; group 3--NT-proBNP > 14275 pg/ml and hs-cTnT < 69.48 ng/l; group 4-
      NT-proBNP > 14275 pg/ml and hs-cTnT > 69.48 ng/l. Survival for each group was
      determined using the Kaplan-Meier method and Cox regression analysis. RESULTS:
      During the follow-up period 16 patients died. According to the ROC curves
      analysis, the cut-off point for hs-cTnT and for NT-proBNP were 69.43 ng/l (AUC =
      0.618; p = 0.04) and 14275 pg/ml (AUC = 0.722; p = 0.003), respectively. In
      univariate Cox analysis, both hs-cTnT (HR = 3.34; p = 0.016) and NT-proBNP (HR =
      5.94; p = 0.01) were predictors of death. In the multivariable Cox proportional
      hazards model, only NT-pro-BNP levels above the cut-off value remained an
      independent predictor of all-cause mortality. The combined elevation of both
      biomarkers did not improve significantly the prognostic value compared with NT
      proBNP alone (HR = 6.15 versus HR =4 .78; p = 0.338). CONCLUSION: NT-pro-BNP is a
      strong predictor of overall mortality in asymptomatic hemodialysis patients. The
      addition of hs-cTnT did not improve the prognostic accuracy compared with NT
      proBNP alone.

PMID- 25571878
TI  - Cysteinyl 1 receptor antagonist montelukast, does not prevent peritoneal membrane
      damage in experimental chronic peritoneal dialysis model in rats.
AB  - BACKGROUND/AIMS: Continuous ambulatory peritoneal dialysis (CAPD) induces
      structural changes in the peritoneal membrane such as fibrosis, vasculopathy and
      angioneogenesis with a reduction in ultrafiltration capacity. Leukotriene (LT)
      receptor antagonists have been found to be effective to prevent fibrosis in some
      nonperitoneal tissues. The aim of this study is to investigate the possible
      beneficial effect of montelukast, a LT receptor antagonist, on peritoneal
      membrane exposed to hypertonic peritoneal dialysis in uremic rats. METHODS: Of
      the 48 male, 5/6 nephrectomized Wistar rats 29 remained alive and were included
      in the study. These studied rats were divided into 3 groups: Group I (n=7) was
      the control group, Group II (n=8) was treated with 20 ml hypertonic PDF
      intraperitoneally daily and Group III was treated with montelukast and similar
      PDF treatment protocol. The morphological and functional changes in the
      peritoneal membrane as well as cytokine expression were compared between groups.
      RESULTS: Submesothelial thickness and the severity of the degree of hyaline
      vasculapathy were more prominent in group III when compared to group I. There
      were no significant differences between group II and other groups in terms of
      submesothelial thickness and the severity of the degree of hyaline vasculapathy.
      Increased expressions of TGF-beta and VEGF in parietal peritoneal membrane were
      found in group II and group III when compared to group I. The amount of TGF-beta
      and VEGF expression were similar in group II and group III. CONCLUSION: This
      study suggests that montelukast treatment does not prevent the peritoneal
      membrane from deleterious effects of hyperosmolar PDF in the uremic environment.

PMID- 25571879
TI  - Aortic arch calcification predicts cardiovascular and all-cause mortality in
      maintenance hemodialysis patients.
AB  - BACKGROUND/AIM: Vascular calcification is associated with cardiovascular risk in
      maintenance hemodialysis (MHD) patients. Previous reports have shown that simple
      assessment of aortic arch calcification (AoAC) using plain radiography is
      associated with cardiovascular mortality in the general population. We conducted
      a prospective study to investigate factors associated with the presence at
      baseline and progression of AoAC in MHD patients and examined its prognostic
      value in a short-term outcome. METHODS: We prospectively evaluated chest X-rays
      in 301 asymptomatic MHD patients. The extent of AoAC was divided into three
      Grades (0, 1, 2+3). Demographic data including age, gender, dialysis vintage, co
      morbidity and biochemical data were assessed and the patients were then followed
      for 3 years. RESULTS: AoAC was observed in 126 patients (41.9%) as Grade 0, in
      112 patients (37.2%) as Grade 1, and in 63 patients (20.9%) as Grade 2 and 3 at
      baseline. An increase in the severity of calcification was associated with older
      male patients who had lower serum albumin levels. During the follow-up period of
      3 years, multivariate Cox proportional hazards analysis revealed that high-grade
      calcification was associated with cardiovascular and all-cause mortality.
      Patients with AoAC were associated with a worse outcome in survival analysis and
      the grade of AAC also influenced their survival. Moreover, all-cause death rates
      were significantly higher in the progression groups than in the non-progression
      groups. CONCLUSIONS: The presence and progression of AoAC assessed by chest X-ray
      were independently associated with mortality in MHD patients. Regular follow-up
      by chest X-ray could be a simple and useful method to stratify mortality risk in
      MHD patients.

PMID- 25571881
TI  - Catalytic partial oxidation coupled with membrane purification to improve
      resource and energy efficiency in syngas production.
AB  - Catalytic partial oxidation coupled with membrane purification is a new process
      scheme to improve resource and energy efficiency in a well-established and large
      scale-process like syngas production. Experimentation in a semi industrial-scale
      unit (20 Nm(3)  h(-1) production) shows that a novel syngas production scheme
      based on a pre-reforming stage followed by a membrane for hydrogen separation, a
      catalytic partial oxidation step, and a further step of syngas purification by
      membrane allows the oxygen-to-carbon ratio to be decreased while maintaining
      levels of feed conversion. For a total feed conversion of 40 %, for example, the
      integrated novel architecture reduces oxygen consumption by over 50 %, with thus
      a corresponding improvement in resource efficiency and an improved energy
      efficiency and economics, these factors largely depending on the air separation
      stage used to produce pure oxygen. 

PMID- 25571880
TI  - Clinical and biochemical manifestations of Cushing's.
AB  - INTRODUCTION: Cushing's syndrome is associated with a number of clinical
      manifestations and co-morbidities which may not resolve even after long-term
      remission leading to excessive mortality. MATERIALS AND METHODS: This review
      summarizes the main manifestations of Cushing's syndrome (active or in remission)
      with particular focus on data from recently published literature. CONCLUSION:
      Obesity and metabolic alterations, hypertension and cardio/cerebrovascular
      complications, hypercoagulability/thromboembolism, neuropsychiatric,
      muscle/skeletal and immune consequences remain the most challenging.
      Cardiovascular consequences and immunosuppression determine the main causes of
      death in Cushing's syndrome necessitating early intervention when possible.

PMID- 25571883
TI  - Safety and Effectiveness of UFE in Fibroids Larger than 10 cm.
AB  - INTRODUCTION: Early literature suggested that the size of the uterus, the size of
      the dominant fibroid, and the amount of applied embolization particles would be
      the risk factors for major postprocedural complications, but recent publications
      have confuted these early results. The purpose of our study was to evaluate
      whether the size of the dominant fibroid would influence the complication rate
      and effectiveness in a large single-center cohort. PATIENTS AND METHODS: From 28
      April 2008 until 31 December 2012, 303 patients had uterine artery embolization
      (UAE). 262 patients had small [largest diameter <10 cm (Group 1)], 41 patients
      had large [largest diameter >10 cm (Group 2)] fibroid. UAE was performed from
      unilateral femoral access using 500-710 and 355-500 um polyvinyl alcohol
      particles. Periprocedural and postprocedural complications and numerical analog
      quality-of-life scores (0-unbearable symptoms; 100-perfect quality of life) were
      listed and statistically analyzed. RESULTS: During the mean follow-up time [7.79
      +/- 5.16 (SD) month], data on 275 patients (275/303 = 90.8 %) were available.
      Quality-of-life score was 33.3 +/- 23.5 and 33.5 +/- 24.1 before, whereas 85.6 +/
      16.0 and 81.5 +/- 23.5 after UAE in Group 1 and Group 2, respectively, (Mann
      Whitney U test one-sided, p = 0.365). There were 4 myoma expulsions, 1 acute
      myomectomy, and 2 acute hysterectomies reported from Group 1, meanwhile 1 myoma
      expulsion, 1 acute myomectomy, and 2 acute hysterectomies were documented from
      Group 2 (NS differences). CONCLUSION: There was no significant difference in the
      effectiveness and in the number of minor and major complications between fibroids
      with <10 cm largest diameter compared to those >10 cm.

PMID- 25571884
TI  - A Novel Technique for the Retrieval of a "Vanished" Nephrostomy Tube.

PMID- 25571882
TI  - Inhibitory action of pristimerin on hypoxia-mediated metastasis involves stem
      cell characteristics and EMT in PC-3 prostate cancer cells.
AB  - The aim of the present study was to investigate whether pristimerin affects the
      bone metastasis, stem cell characteristics and epithelial-mesenchymal transition
      (EMT) of prostate cancer (PCa) PC-3 cells subjected to hypoxia. The PC-3 cells
      were cultured under hypoxia or normoxia for 48 h and were then treated with
      increasing concentrations of pristimerin from 0 to 0.8 umol/l, under normoxia.
      Hypoxia-inducible factor-1alpha (HIF-1alpha) was detected by western blotting.
      Proliferation was assessed with the CCK-8 assay. Transwell invasion assay was
      used to analyze the potency of invasion. Stem cell characteristics were detected
      by sphere formation, colony formation assay and western blotting, including CD44,
      KLF4, OCT4 and AGO2, which are stem cell characteristic-related markers. EMT was
      confirmed by the expression changes of EMT-related markers, including N-cadherin,
      fibronectin, vimentin and ZEB1, which were evaluated by western blotting. The
      addition of pristimerin to the medium reduced the hypoxia-induced PC-3 cell
      proliferation in a dose-dependent manner. Pristimerin effectively inhibited
      hypoxia-induced invasion of the PCa cells in vitro. Moreover, the treatment of
      cells with pristimerin induced the reversal of hypoxia-induced stem cell
      characteristics and EMT, which was confirmed by sphere formation, colony
      formation assay and the expression changes of CSC- and EMT-related markers. The
      reversal of hypoxia-induced stem cell characteristics and EMT in the PCa cells by
      low-dose pristimerin was dose-dependent. These results showed that treatment with
      pristimerin may be a potential strategy for the suppression of hypoxia-induced
      metastasis through the reversal of hypoxia-induced stem cell characteristics and
      EMT in cancer cells, which justifies the potential use of pristimerin as a
      practical chemopreventive approach for patients with PCa.

PMID- 25571886
TI  - CORR Insights(r): do serologic and synovial tests help diagnose infection in
      revision hip arthroplasty with metal-on-metal bearings or corrosion?

PMID- 25571887
TI  - Your best life: mindfulness--the end of suffering.

PMID- 25571885
TI  - Epidemiology, health-related quality of life and economic burden of binge eating
      disorder: a systematic literature review.
AB  - PURPOSE: To perform a systematic review on the epidemiology, the health-related
      quality of life (HRQoL) and economic burden of binge eating disorder (BED).
      METHODS: A systematic literature search of English-language articles was
      conducted using Medline, Embase, PsycINFO, PsycARTICLES, Academic Search
      Complete, CINAHL Plus, Business Source Premier and Cochrane Library. Literature
      search on epidemiology was limited to studies published between 2009 and 2013.
      Cost data were inflated and converted to 2012 US$ purchasing power parities. All
      of the included studies were assessed for quality. RESULTS: Forty-nine articles
      were included. Data on epidemiology were reported in 31, HRQoL burden in 16, and
      economic burden in 7 studies. Diagnosis of BED was made using 4th Edition of The
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria in 46
      studies. Lifetime prevalence of BED was 1.1-1.9% in the general population (DSM
      IV). BED was associated with significant impairment in aspects of HRQoL relating
      to both physical and mental health; the Short Form 36 Physical and Mental
      Component Summary mean scores varied between 31.1 to 47.3 and 32.0 to 49.8,
      respectively. Compared to individuals without eating disorder, BED was related to
      increased healthcare utilization and costs. Annual direct healthcare costs per
      BED patient ranged between $2,372 and $3,731. CONCLUSIONS: BED is a serious
      eating disorder that impairs HRQoL and is related to increased healthcare
      utilization and healthcare costs. The limited literature warrants further
      research, especially to better understand the long-term HRQoL and economic burden
      of BED.

PMID- 25571888
TI  - Not the last word: orthopaedic surgery is lucrative (but evidently not lucrative
      enough).

PMID- 25571889
TI  - Editorial comment--symposium: patient safety: collaboration, communication, and
      physician leadership.

PMID- 25571890
TI  - CORR Insights((r)): Can the Ream and Run Procedure Improve Glenohumeral
      Relationships and Function for Shoulders With the Arthritic Triad?

PMID- 25571892
TI  - Triple-stimulation technique improves the diagnosis of chronic inflammatory
      demyelinating polyradiculoneuropathy.
AB  - INTRODUCTION: A difficult clinical situation occurs when a chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP) patient does not fulfill any of the
      diagnostic criteria. Moreover, nerve conduction studies (NCS) can be consistent
      with axonal neuropathy and lead to misdiagnosis. METHODS: We aimed to assess the
      usefulness of the triple-stimulation technique (TST) for detection of proximal
      conduction blocks (CBs) in patients with axonal-like CIDP. Four patients with
      axonal-like CIDP were studied and compared with 10 typical CIDP patients. In the
      axonal-like group, NCS showed a decrease in compound muscle action potential
      amplitude without features of demyelination, but nerve biopsy showed features of
      demyelination in all 4. RESULTS: Twelve nerves were tested with TST, and 8 CBs
      were detected between the root emergence and the Erb point in the 4 patients, all
      of whom improved after treatment with intravenous immunoglobulin. CONCLUSION: TST
      can identify very proximal CBs in CIDP. The sensitivity of nerve conduction
      studies may be improved by TST in CIDP.

PMID- 25571891
TI  - Affected twins in the familial intracranial aneurysm study.
AB  - BACKGROUND AND PURPOSE: Very few cases of intracranial aneurysms (IAs) in twins
      have been reported. Previous work has suggested that vulnerability to IA
      formation is heritable. Twin studies provide an opportunity to evaluate the
      impact of genetics on IA characteristics, including IA location. We therefore
      sought to examine IA location concordance, multiplicity, and rupture status
      within affected twin-pairs. METHODS: The Familial Intracranial Aneurysm study was
      a multicenter study whose goal was to identify genetic and other risk factors for
      formation and rupture of IAs. The study required at least three affected family
      members or an affected sibling pair for inclusion. Subjects with fusiform
      aneurysms, an IA associated with an AVM, or a family history of conditions known
      to predispose to IA formation, such as polycystic kidney disease, Ehlers-Danlos
      syndrome, Marfan syndrome, fibromuscular dysplasia, or moyamoya syndrome were
      excluded. Twin-pairs were identified by birth date and were classified as
      monozygotic (MZ) or dizygotic (DZ) through DNA marker genotypes. In addition to
      zygosity, we evaluated twin-pairs by smoking status, major arterial territory of
      IAs, and rupture status. Location concordance was defined as the presence of an
      IA in the same arterial distribution (ICA, MCA, ACA, and vertebrobasilar),
      irrespective of laterality, in both members of a twin-pair. The Fisher exact test
      was used for comparisons between MZ and DZ twin-pairs. RESULTS: A total of 16
      affected twin-pairs were identified. Location concordance was observed in 8 of 11
      MZ twin-pairs but in only 1 of 5 DZ twin-pairs (p = 0.08). Three MZ subjects had
      unknown IA locations and comprised the three instances of MZ discordance. Six of
      the 11 MZ twin-pairs and none of the 5 DZ twin-pairs had IAs in the ICA
      distribution (p = 0.03). Multiple IAs were observed in 11 of 22 MZ and 5 of 10 DZ
      twin-pairs. Thirteen (13) of the 32 subjects had an IA rupture, including 10 of
      22 MZ twins. CONCLUSIONS: We found that arterial location concordance was greater
      in MZ than DZ twins, which suggests a genetic influence upon aneurysm location.
      The 16 twin-pairs in the present study are nearly the total of affected twin
      pairs that have been reported in the literature to date. Further studies are
      needed to determine the impact of genetics in the formation and rupture of IAs.

PMID- 25571894
TI  - Travelling for health.

PMID- 25571893
TI  - Interleukin 13-positive mast cells are increased in immunoglobulin G4-related
      sialadenitis.
AB  - Interleukin (IL)-13 is a T helper 2 (Th2) cytokine that plays important roles in
      the pathogenesis of asthma. IL-13 induces hypersensitivity of the airways,
      increased mucous production, elevated serum immunoglobulin (Ig) E levels, and
      increased numbers of eosinophils. Many patients with IgG4-related disease have
      allergic backgrounds and show elevated serum IgE levels and an increase in the
      number of eosinophils. Upregulation of Th2/regulatory T (Treg) cytokines,
      including IL-13, has been detected in affected tissues of patients with IgG4
      related disease. We previously reported that mast cells might be responsible for
      the production of the Th2/Treg cytokines IL-4, IL-10, and transforming growth
      factor (TGF)-beta1 in IgG4-related disease. In this study, immunohistochemical
      analysis showed increased numbers of IL-13-positive mast cells in IgG4-related
      disease, which suggests that mast cells also produce IL-13 and contribute to
      elevation of serum IgE levels and eosinophil infiltration in IgG4-related
      disease. 

PMID- 25571895
TI  - CT characteristics in 24 patients with POEMS syndrome.
AB  - BACKGROUND: POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and
      Skin changes) syndrome is a complicated and rare disease. Systematic research on
      computed tomography (CT) imaging characteristics in POEMS syndrome is scanty. The
      role of CT in diagnosis needs to be assessed. PURPOSE: To retrospectively analyze
      the CT imaging features in 24 patients with POEMS syndrome and evaluate the role
      of CT in diagnosis of this disease. MATERIAL AND METHODS: Twenty-four patients
      with confirmed POEMS syndrome were included in the study. Chest and abdominal CT
      images were analyzed. RESULTS: The three minor diagnostic criteria for POEMS
      syndrome (extravascular volume overload, organomegaly, and bone lesions) can be
      detected effectively by CT. Extravascular volume overload involved multiple
      serous cavities: hydrothorax, hydropericardium, and ascites, which were found in
      79.2%, 41.7%, and 54.2% patients, respectively. The volume of effusion was small
      to moderate. Organomegaly involved multiorgans: hepatomegaly was found in 45.8%
      patients, splenomegaly in 54.2%, and lymphadenopathy in 75% patients.
      Hepatospleen exhibited moderate homogeneous enlargement without local enhanced
      signal after injection of contrast material. Bone lesions were classified into
      three groups: osteosclerotic, osteolytic, and mixed lesions. Osteosclerotic
      lesions, taking multiple, scattered, and variably sized high-density plaque-like
      appearance, were found in 20.8% patients. Osteolytic lesions, exhibiting punched
      out low-density image, were found in 4.2% patients. Mixed ones, holding both
      common characteristics of them, were detected in 8.3% patients. These CT
      abnormalities disappeared after effective treatment. CONCLUSION: CT plays vital
      role in the confirmation of the three minor diagnostic criteria for POEMS
      syndrome: extravascular volume overload, organomegaly, and bone lesions.

PMID- 25571896
TI  - Current Treatment Strategies for Acute Type B Aortic Dissection.
AB  - Acute type B aortic dissection (ATBAD) is a medical emergency that is a common
      occurrence in patients with atherosclerotic disease. The presentation is usually
      severe, with tearing pain that radiates to the back, and various levels of end
      organ ischemia and malperfusion, even rupture, may occur. Everyone agrees that
      prompt and aggressive blood pressure control with beta-blockers and nitroprusside
      is imperative, but when to surgically intervene is still not well characterized.
      However, the advent of minimally invasive stent graft placement has reshaped our
      thoughts regarding therapeutic intervention for ATBAD. This review is an attempt
      to define the current surgical indications for treating ATBAD. 

PMID- 25571897
TI  - Clinical significance of CD44s, CD44v3 and CD44v6 in breast cancer.
AB  - OBJECTIVES: To evaluate levels of CD44 standard variant (CD44s), CD44 variant
      exon 3 (CD44v3) and CD44 variant exon 6 (CD44v6) protein in breast cancer tissue,
      and investigate their relationships with clinicopathological characteristics of
      the disease. METHODS: Immunohistochemistry for CD44s, CD44v3 and CD44v6 was
      retrospectively performed on formalin-fixed paraffin wax-embedded breast cancer
      tissue samples. RESULTS: Tumour tissue samples from 60 patients with breast
      cancer were included. There was a significant relationship between CD44s
      positivity and tumour diameter and lymph node involvement. CD44v6 positivity was
      significantly associated with tumour-node-metastasis (TNM) stage and lymph node
      involvement. There were significant negative correlations between CD44s
      immunopositivity, tumour diameter and TNM stage, and significant positive
      correlations between CD44v6 immunopositivity, tumour diameter and TNM stage.
      CONCLUSIONS: CD44s and CD44v6 appear to play opposing roles in the development of
      breast cancer, but their precise functions and mechanisms of action remain
      unclear.

PMID- 25571898
TI  - Reduction of ovarian reserve in adult patients with dermatomyositis.
AB  - OBJECTIVES: To assess ovarian reserve markers and anti-corpus luteum (anti-CoL)
      antibodies in dermatomyositis (DM) patients. METHODS: Forty female DM patients
      were invited to participate. Exclusion criteria included hormonal contraceptive
      use within the last six months, neoplasia associations, overlapped systemic
      autoimmune diseases, current pregnancy, gynaecological surgery and individual
      choice not to participate. The final experimental group for this cross-sectional
      study included 16 DM patients and 23 healthy controls, each of whom was evaluated
      during the early follicular phase of the menstrual cycle. Values for IgG anti-CoL
      (via immunoblotting), follicle stimulating hormone (FSH), estradiol, inhibin B,
      anti-Mullerian hormone (AMH) serum levels (via ELISA) and sonographic antral
      follicle count (AFC) were determined. RESULTS: DM patients and controls were of
      comparable mean age (p>0.05). The mean age of DM onset was 29.1+/-4.7 years, with
      disease duration of 5.6+/-3.2 years. Menstrual cycle characteristics, comorbidity
      and lifestyle were similar amongst patients in both groups (p>0.05). AMH values
      of <=1ng/mL (p=0.027) and AFC values (p=0.017) were significantly reduced in DM
      patients relative to the control group, whereas serum estradiol levels (p<0.001)
      were higher in DM patients compared to controls. In contrast, serum FSH and
      inhibin B levels, ovarian volumes, and anti-CoL antibody frequency were similar
      in both groups. Differences in AFC and estradiol were determined to be
      significant following Bonferroni correction for multiple testing. CONCLUSIONS: We
      identified a diminished ovarian reserve in DM patients of reproductive age.
      Further studies are necessary to assess the idiopathic inflammatory myopathy
      related factors involved in the ovarian impairment of this patient population.

PMID- 25571899
TI  - Sex-ratio meiotic drive and Y-linked resistance in Drosophila affinis.
AB  - Genetic elements that cheat Mendelian segregation by biasing transmission in
      their favor gain a significant fitness benefit. Several examples of sex-ratio
      meiotic drive, where one sex chromosome biases its own transmission at the cost
      of the opposite sex chromosome, exist in animals and plants. While the distorting
      sex chromosome gains a significant advantage by biasing sex ratio, the autosomes,
      and especially the opposite sex chromosome, experience strong selection to resist
      this transmission bias. In most well-studied sex-ratio meiotic drive systems,
      autosomal and/or Y-linked resistance has been identified. We specifically
      surveyed for Y-linked resistance to sex-ratio meiotic drive in Drosophila affinis
      by scoring the sex ratio of offspring sired by males with a driving X and one of
      several Y chromosomes. Two distinct types of resistance were identified: a
      restoration to 50/50 sex ratios and a complete reversal of sex ratio to all sons.
      We confirmed that fathers siring all sons lacked a Y chromosome, consistent with
      previously published work. Considerable variation in Y-chromosome morphology
      exists in D. affinis, but we showed that morphology does not appear to be
      associated with resistance to sex-ratio meiotic drive. We then used two X
      chromosomes (driving and standard) and three Y chromosomes (susceptible,
      resistant, and lacking) to examine fertility effects of all possible
      combinations. We find that both the driving X and resistant and lacking Y have
      significant fertility defects manifested in microscopic examination of testes and
      a 48-hr sperm depletion assay. Maintenance of variation in this sex-ratio meiotic
      drive system, including both the X-linked distorter and the Y-resistant effects,
      appear to be mediated by a complex interaction between fertility fitness and
      transmission dynamics. 

PMID- 25571901
TI  - Real-Time GnRH Gene Transcription in GnRH Promoter-Driven Luciferase-Expressing
      Transgenic Mice: Effect of Kisspeptin.
AB  - Pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) is
      indispensable for controlling proper pituitary gonadotrope functions; however,
      the mechanism underlying GnRH pulse generation remains largely unknown. It is
      important to understand the cellular oscillator in individual GnRH neurons and
      temporal synchronization among GnRH neurons. In this brief review, we summarize
      our recent findings on episodic GnRH gene transcription at the single GnRH neuron
      level and in synchronized multicellular burst in relation to the temporal pattern
      of GnRH secretion. We also detail the effects of kisspeptin on ultradian rhythmic
      GnRH gene transcription and secretion. We extend our discussion to the
      hierarchical interaction between circadian and ultradian rhythms. Taken together,
      the current review elucidates the genomic control of GnRH pulse generation in
      hypothalamic neurons. 

PMID- 25571900
TI  - Unusual regulation of splicing of the cholinergic locus in Caenorhabditis
      elegans.
AB  - The essential neurotransmitter acetylcholine functions throughout the animal
      kingdom. In Caenorhabditis elegans, the acetylcholine biosynthetic enzyme
      [choline acetyltransferase (ChAT)] and vesicular transporter [vesicular
      acetylcholine transporter (VAChT)] are encoded by the cha-1 and unc-17 genes,
      respectively. These two genes compose a single complex locus in which the unc-17
      gene is nested within the first intron of cha-1, and the two gene products arise
      from a common pre-messenger RNA (pre-mRNA) by alternative splicing. This genomic
      organization, known as the cholinergic gene locus (CGL), is conserved throughout
      the animal kingdom, suggesting that the structure is important for the regulation
      and function of these genes. However, very little is known about CGL regulation
      in any species. We now report the identification of an unusual type of splicing
      regulation in the CGL of C. elegans, mediated by two pairs of complementary
      sequence elements within the locus. We show that both pairs of elements are
      required for efficient splicing to the distal acceptor, and we also demonstrate
      that proper distal splicing depends more on sequence complementarity within each
      pair of elements than on the sequences themselves. We propose that these sequence
      elements are able to form stem-loop structures in the pre-mRNA; such structures
      would favor specific splicing alternatives and thus regulate CGL splicing. We
      have identified complementary elements at comparable locations in the genomes of
      representative species of other animal phyla; we suggest that this unusual
      regulatory mechanism may be a general feature of CGLs. 

PMID- 25571902
TI  - Peroxisystem: harnessing systems cell biology to study peroxisomes.
AB  - In recent years, high-throughput experimentation with quantitative analysis and
      modelling of cells, recently dubbed systems cell biology, has been harnessed to
      study the organisation and dynamics of simple biological systems. Here, we
      suggest that the peroxisome, a fascinating dynamic organelle, can be used as a
      good candidate for studying a complete biological system. We discuss several
      aspects of peroxisomes that can be studied using high-throughput systematic
      approaches and be integrated into a predictive model. Such approaches can be used
      in the future to study and understand how a more complex biological system, like
      a cell and maybe even ultimately a whole organism, works. 

PMID- 25571903
TI  - MSCs seeded on bioengineered scaffolds improve skin wound healing in rats.
AB  - Growing evidence has shown the promise of mesenchymal stromal cells (MSCs) for
      the treatment of cutaneous wound healing. We have previously demonstrated that
      MSCs seeded on an artificial dermal matrix, Integra (Integra Lifesciences Corp.,
      Plainsboro, NJ) enriched with platelet-rich plasma (Ematrix) have enhanced
      proliferative potential in vitro as compared with those cultured on the scaffold
      alone. In this study, we extended the experimentation by evaluating the efficacy
      of the MSCs seeded scaffolds in the healing of skin wounds in an animal model in
      vivo. It was found that the presence of MSCs within the scaffolds greatly
      ameliorated the quality of regenerated skin, reduced collagen deposition,
      enhanced reepithelization, increased neo-angiogenesis, and promoted a greater
      return of hair follicles and sebaceous glands. The mechanisms involved in these
      beneficial effects were likely related to the ability of MSCs to release
      paracrine factors modulating the wound healing response. MSC-seeded scaffolds, in
      fact, up-regulated matrix metalloproteinase 9 expression in the extracellular
      matrix and enhanced the recruitment of endogenous progenitors during tissue
      repair. In conclusion, the results of this study provide evidence that the
      treatment with MSC-seeded scaffolds of cutaneous wounds contributes to the
      recreation of a suitable microenvironment for promoting tissue
      repair/regeneration at the implantation sites. 

PMID- 25571904
TI  - Severe scoliosis associated with the WNT10A mutation.

PMID- 25571905
TI  - Attentional processes in low-socioeconomic status bilingual children: are they
      modulated by the amount of bilingual experience?
AB  - Recent research indicates that bilingual children are more proficient in
      resolving cognitive conflict than monolinguals. However, the replicability of
      such findings has been questioned, with poor control of participants'
      socioeconomic status (SES) as a possible confounding factor. Two experiments are
      reported here, in which the main attentional functions and pragmatic ability of
      54 bilingual and 56 monolingual low-SES children were assessed (Experiment 1: 6-
      to 12-year-olds; Experiment 2: 6- to 8-year-olds). A language-switching task was
      also employed, to measure bilingual proficiency. Overall, the monolingual and
      bilingual groups did not differ significantly in any of the tasks employed,
      although the ability to resolve conflict was related to children's level of
      bilingual experience. 

PMID- 25571906
TI  - Multiloculated postinfarction ventricular septal defect.

PMID- 25571907
TI  - Hybrids of Shigatoxigenic and Enterotoxigenic Escherichia coli (STEC/ETEC) Among
      Human and Animal Isolates in Finland.
AB  - Diarrhoeagenic Escherichia coli (DEC) cause serious foodborne infections in
      humans. Total of 450 Shigatoxigenic E. coli (STEC) strains isolated from humans,
      animals and environment in Finland were examined by multiplex PCR targeting the
      virulence genes of various DEC pathogroups simultaneously. One per cent (3/291)
      of the human STEC and 14% (22/159) of the animal and environmental STEC had genes
      typically present in enterotoxigenic E. coli (ETEC). The strains possessed genes
      encoding both Shiga toxin 1 and/or 2 (stx1 and/or stx2 ) and ETEC-specific heat
      stable (ST) enterotoxin Ia (estIa). The identified stx subtypes were stx1a,
      stx1c, stx2a, stx2d and stx2g. The three human STEC/ETEC strains were isolated
      from the patients with haemolytic uraemic syndrome and diarrhoea and from an
      asymptomatic carrier. The animal STEC/ETEC strains were isolated from cattle and
      moose. The human and animal STEC/ETEC strains belonged to 11 serotypes, of which
      O2:H27, O15:H16, O101:H-, O128:H8 and O141:H8 have previously been described to
      be associated with human disease. Identification of multiple virulence genes
      offers further information for assessing the virulence potential of STEC and
      other DEC. The emergence of novel hybrid pathogens should be taken into account
      in the patient care and epidemiological surveillance.

PMID- 25571909
TI  - Primary cutaneous follicle center lymphoma in a patient with WHIM syndrome.

PMID- 25571908
TI  - Disseminated adenovirus disease in heart transplant recipient presenting with
      conjunctivitis.
AB  - We report a 65-year-old heart transplant recipient who presented with
      conjunctivitis, likely acquired from a family member who worked at a daycare
      center during an outbreak of conjunctivitis. He developed a severe adenoviral
      pneumonitis, which was successfully treated with intravenous cidofovir combined
      with a reduction of immunosuppression. 

PMID- 25571910
TI  - Effect of particle size on calcium release and elevation of pH of endodontic
      cements.
AB  - BACKGROUND/AIM: Elevation of pH and calcium ion release are of great importance
      in antibacterial activity and the promotion of dental soft and hard tissue
      healing process. In this study, we evaluated the effect of particle size on the
      elevation of pH and the calcium ion release from calcium silicate-based dental
      cements. MATERIAL AND METHODS: Twelve plastic tubes were divided into three
      groups, filled with white mineral trioxide aggregate (WMTA), WMTA plus 1%
      methylcellulose, and nano-modified WMTA (nano-WMTA), and placed inside flasks
      containing 10 ml of distilled water. The pH values were measured using a pH
      sensor 3, 24, 72, and 168 h after setting of the cements. The calcium ion release
      was measured using an atomic absorption spectrophotometer with same sample
      preparation method. Data were subjected to two-way analysis of variance (anova)
      followed by post hoc Tukey tests with significance level of P < 0.05. RESULTS:
      Nano-WMTA showed significant pH elevation only after 24 h (P < 0.05) compared
      with WMTA, and after 3, 24, and 72 h compared with WMTA plus 1% methylcellulose
      (P < 0.05). Nano-WMTA showed significantly higher calcium ion release values
      compared to the other two groups (P < 0.05). CONCLUSIONS: Nano-modification of
      WMTA remarkably increased the calcium ion release at all time intervals
      postsetting, which can significantly influence the osteogenic properties of human
      dental pulp cells and as a consequence enhance mineralized matrix nodule
      formation to achieve desirable clinical outcomes. However, the increase in pH
      values mainly occurred during the short time postsetting. Addition of 1%
      methylcellulose imposed a delay in elevation of pH and calcium ion release by
      WMTA.

PMID- 25571912
TI  - Identification of dysregulated microRNAs in triple-negative breast cancer
      (review).
AB  - Triple-negative breast cancer (TNBC) is defined by the absence of expression of
      the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth
      factor receptor 2 (HER2). TNBC exhibits a more aggressive phenotype and a poorer
      clinical outcome compared to other breast cancer subgroups, accounting for 15-20%
      of total breast cancer cases. To date, the treatment strategies for TNBC are
      limited to surgery, chemotherapy and radiation, owing to the lack of effective
      therapeutic targets. Therefore, it is important to identify specific targets for
      TNBCs. MicroRNAs (miRNAs), a family of small non-coding RNAs regulating gene
      expression, are an emerging class of regulators of various biological processes,
      including cell proliferation, invasion, epithelial-mesenchymal transition (EMT)
      and drug resistance. Actually, miRNAs may serve as a novel therapeutic target in
      TNBC, and here we review current correlated researches and provide our own
      profiling results for the miRNAs expressed in TNBC cell lines. The present study
      offers an additional insight into the potential miRNAs involved in the regulation
      of TNBC.

PMID- 25571911
TI  - High glucose induces the release of endothelin-1 through the inhibition of
      hydrogen sulfide production in HUVECs.
AB  - Hydrogen sulfide (H(2)S) has recently been identified as an endogenous gaseous
      signaling molecule. In the vascular system, the formation of H(2)S is catalyzed
      by cystathionine gamma-lyase (CSE). Previous studies have demonstrated the
      protective effects of H(2)S on ischemic injury in various types of tissue.
      However,, little is known about the role of H(2)S in diabetes-associated vascular
      diseases. Thus, the aim of the present study was to examine the possible role of
      H(2)S in high glucose-induced vascular dysfunction, and to explore the underlying
      mechanisms. Human umbilical vein endothelial cells (HUVECs) were isolated from
      human umbilical veins. The levels of H(2)S following treatment with various
      levels of glucose were determined and the secretion of endothelin-1 (ET-1) was
      measured by ELISA. The mRNA and protein expression of CSE in the HUVECs was
      determined by real-time RT-PCR and western blot analysis, respectively. Treatment
      with high glucose (25 mmol/l) for 48 h significantly increased the secretion of
      ET-1 by HUVECs, with the concomitant suppression of H(2)S production and CSE
      protein expression. The increase in exogenous H(2)S levels through the
      administration of sodium hydrosulfide (NaHS) attenuated the high glucose-induced
      downregulation of CSE protein expression, and significantly inhibited the
      secretion of ET-1. These results suggest that the downregulation of CSE protein
      expression and the subsequent decrease in H(2)S production play a role in high
      glucose-induced vascular dysfunction possibly by increasing the secretion of ET-1
      by endothelial cells.

PMID- 25571913
TI  - Therapeutic delivery of cyclin-A2 via recombinant adeno-associated virus serotype
      9 restarts the myocardial cell cycle: an in vitro study.
AB  - Cyclin-A2, which is downregulated following birth, has previously been
      established as a key regulator of the cell cycle. The present study aimed to
      detect the effects of cyclin-A2 on myocardial cells by using recombinant adeno
      associated virus 9 (rAAV9). Sixty mice were selected and randomly divided into
      two groups (n=30). The control group were injected with saline and the
      experimental group were transfected with the rAAV9-cyclinA2-CMV vector by
      intravenous injection into the tail vein. Tissues were harvested at two and four
      weeks following injection. Cyclin-A2 expression levels and localization were
      evaluated using western blot and immunohistochemical analyses. DNA synthesis and
      mitosis in the myocardium were confirmed by analyzing proliferating cell nuclear
      antigen (PCNA) and phospho-histone H3 (H3P) expression levels. Expression of
      Cyclin-A2 in the myocardium commenced two weeks following tail vein injection in
      the cyclin-A2-treated group, while no expression was observed in the control
      group. Four weeks following injection, expression levels of cyclin-A2 were higher
      than those observed at two weeks following injection into the myocardium (two
      weeks: 0.146+/-0.013 vs. 27.1+/-3.33%, P<0.001; four weeks: 0.142+/-0.107 vs.
      74.4+/-3.36%, P<0.001). PCNA displayed increased expression levels in the cyclin
      A2-treated group (two weeks: 13.1+/-0.54 vs. 65.8+/-3.44%, P<0.001; four weeks:
      13.2+/-0.55 vs. 71.2+/-1.58%, P<0.001); however, no change was observed in those
      of the control group. By contrast, no significant difference was observed in
      mitosis marker H3P expression levels between the two groups. Immunohistochemical
      analysis of cyclin-A2 indicated cytoplasmic, but not nuclear, localization.
      cyclin-A2 and PCNA expression levels in the liver, lung and kidney showed no
      significant difference between the two groups (P>0.05). It was therefore
      concluded that the delivery of cyclin-A2 via rAAV9 to the mouse myocardium
      restarted the myocardial cell cycle, thereby establishing steady and specific
      expression in the myocardium. Furthermore, the effect of Cyclin-A2 on the
      myocardium may provide a novel method for achieving cardiac regeneration
      following cardiac injury.

PMID- 25571914
TI  - Investigating the use of an antiscatter grid in chest radiography for average
      adults with a computed radiography imaging system.
AB  - OBJECTIVE: The aim of this study was to investigate via simulation a proposed
      change to clinical practice for chest radiography. The validity of using a
      scatter rejection grid across the diagnostic energy range (60-125 kVp), in
      conjunction with appropriate tube current-time product (mAs) for imaging with a
      computed radiography (CR) system was investigated. METHODS: A digitally
      reconstructed radiograph algorithm was used, which was capable of simulating CR
      chest radiographs with various tube voltages, receptor doses and scatter
      rejection methods. Four experienced image evaluators graded images with a grid (n
      = 80) at tube voltages across the diagnostic energy range and varying detector
      air kermas. These were scored against corresponding images reconstructed without
      a grid, as per current clinical protocol. RESULTS: For all patients, diagnostic
      image quality improved with the use of a grid, without the need to increase tube
      mAs (and therefore patient dose), irrespective of the tube voltage used.
      Increasing tube mAs by an amount determined by the Bucky factor made little
      difference to image quality. CONCLUSION: A virtual clinical trial has been
      performed with simulated chest CR images. RESULTS indicate that the use of a grid
      improves diagnostic image quality for average adults, without the need to
      increase tube mAs, even at low tube voltages. ADVANCES IN KNOWLEDGE: Validated
      with images containing realistic anatomical noise, it is possible to improve
      image quality by utilizing grids for chest radiography with CR systems without
      increasing patient exposure. Increasing tube mAs by an amount determined by the
      Bucky factor is not justified.

PMID- 25571915
TI  - The potential use of ultra-low radiation dose images in digital mammography--a
      clinical proof-of-concept study in craniocaudal views.
AB  - OBJECTIVE: To estimate the potential of low-dose images in digital mammography by
      analysing the effect of substantial dose reduction in craniocaudal (CC) views on
      clinical performance. METHODS: At routine mammography, additional CC views were
      obtained with about 10% of the standard dose. Five radiologists retrospectively
      read the standard [mediolateral oblique (MLO) + CC] and combination low-dose
      mammograms (standard MLO + low-dose CC). If present, lesion type, conspicuity and
      suggested work-up were recorded. Final diagnoses were made by histology or follow
      up. A t-test or chi(2) test was used to compare results. RESULTS: 421 cases were
      included, presenting 5 malignancies, 66 benign lesions and multiple non-specific
      radiologic features. Using MLO with low-dose CC, all lesions were detected by at
      least one reader, but altogether less often than with standard mammography
      (sensitivity, 73.9% vs 81.5%). Missed lesions concerned all types. Lesions
      detected with both protocols were described similarly (p = 0.084) with comparable
      work-up recommendations (p = 0.658). CONCLUSION: Mammography with ultra-low-dose
      CC images particularly influences detection. While sensitivity decreased,
      specificity was unaffected. In this proof-of-concept study a lower limit was to
      be determined that is not intended nor applicable for clinical practice. This
      should facilitate further research in optimization of a low-dose approach, which
      has potential in a relatively young and largely asymptomatic population. ADVANCES
      IN KNOWLEDGE: Tungsten/silver-acquired mammography images might facilitate
      substantial dose reduction. Ultra-low-dose CC images reduce sensitivity, but not
      specificity. Low-dose images have potential in a largely young and asymptomatic
      population; a baseline is set for further research in optimization of a low-dose
      approach.

PMID- 25571916
TI  - Time to demand dosimetry for molecular radiotherapy?
AB  - Molecular radiotherapy (MRT) has been used clinically for around 75 years.
      Despite this long history of clinical use, there is no established dosimetry
      practice for calculating the absorbed dose delivered to tumour targets or to
      organs at risk. As a result, treatment protocols have often evolved based on
      experience with relatively small numbers of patients, each receiving a similar
      administered activity but, potentially, widely varying doses. This is in stark
      contrast to modern external-beam radiotherapy practice. This commentary describes
      some of the barriers to MRT dosimetry and gives some opinions on the way forward.

PMID- 25571917
TI  - Ubenimex inhibits cell proliferation, migration and invasion in renal cell
      carcinoma: the effect is autophagy-associated.
AB  - Ubenimex is a low-molecular-weight dipeptide with the ability to inhibit
      aminopeptidase N (APN) activity, enhance the function of immunocompetent cells
      and confer antitumor effects. We sought to characterize the effects of ubenimex
      on renal cell carcinoma (RCC). The 786-O and OS-RC-2 human RCC cell lines were
      positive for APN expression and ubenimex decreased APN activity without affecting
      the expression. Ubenimex suppressed the proliferation of both cell lines in a
      concentration-dependent manner, as assessed by curve growth analysis and WST-8
      proliferation assay. Wound healing and Matrigel invasion assays demonstrated that
      the migration and invasion of the RCC cells were also markedly suppressed by
      ubenimex. Furthermore, ubenimex increased the mortality of both RCC cell lines as
      determined by the LDH cytotoxicity assay. This affect was accompanied by
      increased levels of LC3B with no apparent effect on Caspase3; and we observed
      that autophagy increased significantly after ubenimex treatment in both RCC cell
      lines by electron microscopy. Moreover, rapamycin enhanced the cytotoxic effect
      of ubenimex, while 3-methyladenine reversed the effect, indicating that ubenimex
      cytotoxicity occured through an autophagy-related mechanism. To further assess
      the potential applicability of ubenimex in the treatment of RCC, we performed
      immunohistochemistry using tissue microarrays representing 76 RCC patients that
      underwent radical nephrectomy. The results showed that APN was expressed in most,
      but not all of the RCC tissues and that the expression was reduced in RCC as
      compared to the normal kidney tissues, suggesting a potential role for APN in RCC
      development. Collectively, these results indicated that ubenimex inhibits
      proliferation, migration and invasion of RCC cells. Ubenimex may induce
      autophagy, which may be associated with its effect on the growth arrest and the
      cell death of RCC cells.

PMID- 25571918
TI  - Ochratoxin A and ochratoxin-producing fungi on cereal grain in China: a review.
AB  - The mycotoxin ochratoxin A (OTA) is known to be the main contaminant of cereal
      grain and has become increasingly important in recent years. Therefore, a survey
      of ochratoxigenic fungi and OTA contamination in China is a special challenge.
      This paper summarises data on cereals and moulds (Aspergillus niger, Penicillium
      verrucosum, Aspergillus ochraceus, for example) and on grain and OTA from 1973 by
      searching Chinese information databases (NCKI, VIP, DuXiu etc.), calculating the
      OTA-producing mould detection rate, referring to sampling locations, latitude and
      temperature, and also combining six grain-producing areas of ochratoxigenic fungi
      and OTA positive rate through a comprehensive analysis. It is concluded that in
      China rice (excluding shell rice) has less OTA contamination than wheat or maize.
      The contamination of cereal grains with Aspergillus section Nigri (formerly of
      the A. niger group) is a serious problem in China, and these fungi may be the
      main ochratoxigenic fungi on cereals.

PMID- 25571919
TI  - Alterations in enhancer of zeste homolog 2, matrix metalloproteinase-2 and tissue
      inhibitor of metalloproteinase-2 expression are associated with ex vivo and in
      vitro bone metastasis in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) has a high potential for bone metastasis; however, the
      molecular mechanisms underlying this metastasis have remained to be elucidated.
      The present study aimed to explore the expression levels of enhancer of zeste
      homolog 2 (EZH2), matrix metalloproteinase-2 (MMP2) and tissue inhibitor of
      metalloproteinase-2 (TIMP2) as determinants of RCC-associated bone metastasis.
      Their expression was evaluated in a newly generated RCC cell subline that has a
      high potential for bone metastasis, in tissue specimens from metastasized bone
      tissues from patients with RCC and in RCC tissues without metastasis. A total of
      25 RCC tissue specimens without metastasis and 13 RCC tissue specimens with bone
      metastasis were acquired for immunohistochemical analysis of EZH2, MMP2 and TIMP2
      protein expression. The expression levels of EZH2, MMP2 and TIMP2 mRNA and
      protein were analyzed in the ACHN and ACHN-BO5 cell lines using western blot and
      reverse transcription polymerase chain reaction (PCR) analyses. Methylation
      specific PCR was also used to analyze TIMP2 promoter methylation. EZH2 and MMP2
      proteins were found to be expressed at higher levels in tissues from patients
      where RCC had metastasized to the bone as compared with those in RCC patients
      without metastasis, whereas there was no significant difference in the expression
      of TIMP2 protein between the two tissues. Furthermore, the expression of EZH2
      protein was correlated with MMP2 expression, but there was no significant
      correlation between the expression of EZH2 and TIMP2 proteins. The in vitro
      results using cell lines confirmed the ex vivo findings, indicating that the
      expression levels of EZH2 and MMP2 protein and mRNA were higher in ACHN-BO5 cells
      than those in ACHN cells. By contrast, TIMP2 protein and mRNA expression levels
      were lower in ACHN-BO5 cells than those in the parental ACHN cells. The TIMP2
      promoter was highly methylated in ACHN-BO5 cells compared with that in ACHN
      cells. Upregulation of EZH2, MMP2 and TIMP2 expression was correlated with
      metastasis of RCC to bone tissues ex vivo and in vitro. Further studies are
      required in order to elucidate the mechanism underlying the altered expression of
      these genes.

PMID- 25571921
TI  - A study of influences of the workers' compensation and injury management
      regulations on aviation safety at a workplace.
AB  - As the aviation industries developed, so too did the recognition that there must
      be an effective regulatory framework to address issues related to the workers'
      compensation and rehabilitation. All employees would like to work and return home
      safely from their workplace. Therefore, the efficient management of workplace
      injury and disease reduces the cost of aviation operations and improves flight
      safety. Workers' compensation and injury management laws regulate a majority of
      rehabilitation and compensation issues, but achieving an injury-free workplace
      remains a major challenge for the regulators. This paper examines the clauses of
      the workers' compensation and injury management laws of Western Australia related
      to workplace safety, compensation, and rehabilitations of the injured workers. It
      also discusses various provisions of common law under the relevant workers'
      health injury management legislations. 

PMID- 25571920
TI  - Anti-infective potential of caffeic acid and epicatechin 3-gallate isolated from
      methanol extract of Euphorbia hirta (L.) against Pseudomonas aeruginosa.
AB  - Euphorbia hirta (L.) plant is traditionally used in Malaysia for the treatment of
      gastrointestinal, bronchial and respiratory ailments caused by nosocomial
      infectious agents. Bioactivity-guided fractionation of the methanol extract of
      the aerial parts of E. hirta and analysis using high-performance liquid
      chromatography have led to the isolation of two antibacterial compounds. These
      compounds were identified as caffeic acid (CA) and (-)-epicatechin 3-gallate
      (ECG) based on spectroscopic analyses and comparison with previously published
      data. Using broth microdilution method, both ECG and CA had demonstrated
      significant minimum inhibitory concentration of 15.6 and 31.3 MUg/mL
      respectively, against Pseudomonas aeruginosa. Time-kill assessment of ECG and CA
      displayed bactericidal effect on P. aeruginosa cells.

PMID- 25571922
TI  - Non-invasive wave reflection quantification in patients with reduced ejection
      fraction.
AB  - The non-invasive quantification of arterial wave reflection is an increasingly
      important concept in cardiovascular research. It is commonly based on pulse wave
      analysis (PWA) of aortic pressure. Alternatively, wave separation analysis (WSA)
      considering both aortic pressure and flow waveforms can be applied. Necessary
      estimates of aortic flow can be measured by Doppler ultrasound or provided by
      mathematical models. However, this approach has not been investigated intensively
      up to now in subjects developing systolic heart failure characterized by highly
      reduced ejection fraction (EF). We used non-invasively generated aortic pressure
      waveforms and Doppler flow measurements to derive wave reflection parameters in
      61 patients with highly reduced and 122 patients with normal EF. Additionally we
      compared these readings with estimates from three different flow models known
      from literature (triangular, averaged, Windkessel). After correction for
      confounding factors, all parameters of wave reflection (PWA and WSA) were
      comparable for patients with reduced and normal EF. Wave separations assessed
      with the Windkessel based model were similar to those derived from Doppler flow
      in both groups. The averaged waveform performed poorer in reduced than in normal
      EF, whereas triangular flow represented a better approximation for reduced EF.
      Overall, the non-invasive assessment of WSA parameters based on mathematical
      models compared to ultrasound seems feasible in patients with reduced EF. 

PMID- 25571923
TI  - Phenolic sulfates as new and highly abundant metabolites in human plasma after
      ingestion of a mixed berry fruit puree.
AB  - Bioavailability studies are vital to assess the potential impact of bioactive
      compounds on human health. Although conjugated phenolic metabolites derived from
      colonic metabolism have been identified in the urine, the quantification and
      appearance of these compounds in plasma is less well studied. In this regard, it
      is important to further assess their potential biological activity in vivo. To
      address this gap, a cross-over intervention study with a mixed fruit puree
      (blueberry, blackberry, raspberry, strawberry tree fruit and Portuguese
      crowberry) and a standard polyphenol-free meal was conducted in thirteen
      volunteers (ten females and three males), who received each test meal once, and
      plasma metabolites were identified by HPLC-MS/MS. Sulfated compounds were
      chemically synthesised and used as standards to facilitate quantification. Gallic
      and caffeic acid conjugates were absorbed rapidly, reaching a maximum
      concentration between 1 and 2 h. The concentrations of sulfated metabolites
      resulting from the colonic degradation of more complex polyphenols increased in
      plasma from 4 h, and pyrogallol sulfate and catechol sulfate reached
      concentrations ranging from 5 to 20 MUm at 6 h. In conclusion, phenolic sulfates
      reached high concentrations in plasma, as opposed to their undetected parent
      compounds. These compounds have potential use as biomarkers of polyphenol intake,
      and their biological activities need to be considered. 

PMID- 25571925
TI  - A case report of progressive obstruction of Ex-PRESS miniature glaucoma shunt
      after transient flat anterior chamber and treatment using Nd:YAG laser.
AB  - BACKGROUND: We report a case of Ex-PRESS miniature glaucoma shunt obstruction
      resulting from progressive iris synechial formation after transient anterior
      chamber shallowing. CASE PRESENTATION: A 68-year-old woman with pseudoexfoliation
      glaucoma in her right eye underwent filtration surgery with implantation of the
      Ex-PPESS shunt (model P-50, Alcon Japan, Tokyo, Japan) in combination with intra
      surgical 0.04% mitomycin C use. After the anterior chamber injection of
      viscoelastic material and 100% sulfur hexafluoride gas for treatment of early
      postoperative over filtration, the intraocular pressure (IOP) was controlled
      between 9 and 12 mmHg. On postoperative day 121, gonioscopy showed that synechial
      formation around the shunt obstructed the axial port leaving the relief port
      opened. On postoperative day 274, the intraocular pressure increased to 40 mmHg
      and synechiae obstructed both the axial and relief ports. Dispersion of iris
      tissue by neodymium:yttrium-aluminium-garnet (Nd:YAG) laser (2 mJ, one shot to
      each port) opened both ports and immediately lowered the IOP, leaving peripheral
      anterior synechiae around the shunt. Up to postoperative day 400, the IOP was
      controlled between 13 and 15 mmHg, and the cystic bleb was maintained.
      CONCLUSION: The synechiae formed gradually extends around the shunt's shaft and
      can result in later external obstruction of the relief port. The current case
      requires further follow-up since synechiae remaining around the shaft can cause
      future obstruction. We emphasize the fact that, if the iris synechiae to the
      shunt once formed, it can progress and obstruct the shunt ports later.

PMID- 25571924
TI  - Functional capacity of reconstituted blood in 1:1:1 versus 3:1:1 ratios: a
      thrombelastometry study.
AB  - INTRODUCTION: Different transfusion ratio concepts of packed red blood cells
      (pRBCs), fresh frozen plasma (FFP) and platelets (PLTs) have been implemented in
      trauma care, but the optimal ratios are still discussed. In this study the
      hemostatic potential of two predefined ratios was assessed by using an in vitro
      thrombelastometric approach. Furthermore, age effects of reconstituted blood were
      analyzed. METHODS: Whole blood (WB) of voluntary donors was separated into pRBCs,
      FFP and PLTs and reconstituted into the ratios 1:1:1 and 3:1:1 at day 1, 4, 14,
      and 24. Standard blood count, electrolytes and coagulation proteins were
      quantified. The functional coagulation in ratio- and age-specific groups was
      evaluated using rotational thromboelastometry (ROTEM). RESULTS: Several
      coagulation factors reduced significantly in the 3:1:1 ratio and were consistent
      with increased INR, decelerated clot formation times and A10 (amplitude 10
      minutes after clotting time (CT)), flattened alpha-angle during the EXTEM and
      diminished MCF for distinct time points during the INTEM, FIBTEM and APTEM
      assays. With rising age of pRBCs the pH, sodium and potassium reached non
      physiological levels. CONCLUSION: Under standardized in vitro conditions the
      higher amount of pRBCs in the 3:1:1 ratio diluted coagulation factors
      significantly on the expense of its functional coagulation capacity as revealed
      by ROTEM results. Thus, the coagulation functionality of the 1:1:1 ratio
      predominated.

PMID- 25571926
TI  - Epidemiology of Rett syndrome in Serbia: prevalence, incidence and survival.
AB  - BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder that
      represents the second most common cause of mental retardation in females.
      However, incidence and prevalence of RTT are scarcely reported. METHODS: A
      retrospective study included all patients with RTT diagnosed between 1981 and
      2012 in Serbia. Estimation of incidence and prevalence was calculated on the
      basis of vital statistics reported by Statistical Office of Republic of Serbia.
      RESULTS: From 1981 to 2012, RTT has been diagnosed in 102 girls in Serbia.
      Incidence of RTT in Serbia is estimated at 0.586:10,000 female live births. We
      estimated the prevalence of RTT in population of females younger than 19 years at
      1:8,439. Death occurred in 19 patients (18.63%), with pneumonia as the most
      common cause. The lethal outcome by the age of 12 years could be expected for 11%
      of patients. The mean age at diagnosis was 3.5 years and we have confirmed a
      significant trend towards earlier dianosis during studied period. CONCLUSIONS:
      Rett syndrome incidence in Serbia is in accordance with reports from other
      countries. Serbian RTT patients have increased risk for early death when compared
      to patients in more developed countries, most commonly due to pneumonia. There
      was significant trend towards early diagnosis of RTT in Serbia over recent
      decades.

PMID- 25571927
TI  - Estimating the information value of polymorphic sites using pooled sequences.
AB  - BACKGROUND: High-throughput sequencing is a cost effective method for identifying
      genetic variation, and it is currently in use on a large scale across the field
      of biology, including ecology and population genetics. Correctly identifying
      variable sites and allele frequencies from sequencing data remains challenging,
      in large part due to artifacts and biases inherent in the sequencing process.
      Selecting variants that are diagnostic is commonly done using diversity
      statistics like FST, but these measures are not ideal for the task. RESULTS:
      Here, we develop a method that directly calculates the expected amount of
      information gained from observing each variant site. We then develop and
      implement a conservative estimator that takes into account uncertainity
      introduced by sampling bias and sequencing error. This estimator is applied to
      simulated and real sequencing data, and we discuss how it performs compared to
      the commonly used existing methods for identifying diagnostic polymorphisms.
      CONCLUSION: The expected information content gives an easy to interpret measure
      for the usefulness of variant sites. The results show that we achieve a clear
      separation between true variants and noise, allowing us to select candidate sites
      with a high degree of confidence.

PMID- 25571928
TI  - The highly polymorphic cyclophilin A-binding loop in HIV-1 capsid modulates viral
      resistance to MxB.
AB  - BACKGROUND: The human myxovirus-resistance protein B (MxB, also called Mx2) was
      recently reported to inhibit HIV-1 infection by impeding the nuclear import and
      integration of viral DNA. However, it is currently unknown whether there exist
      MxB-resistant HIV-1 strains in the infected individuals. Answer to this question
      should address whether MxB exerts an inhibitory pressure on HIV-1 in vivo and
      whether HIV-1 has evolved to evade MxB inhibition. FINDINGS: We have examined ten
      transmitted founder (T/F) HIV-1 strains for their sensitivity to MxB inhibition
      by infecting CD4+ T cell lines SupT1 and PM1 that were stably transduced to
      express MxB. Two T/F stains, CH040.c and RHPA.c, were found resistant and this
      resistance phenotype was mapped to the amino acid positions 87 and 208 in viral
      capsid. The H87Q mutation is located in the cyclophilin A (CypA) binding loop and
      has a prevalence of 21% in HIV-1 sequences registered in HIV database. This
      finding prompted us to test other frequent amino acid variants in the CypA
      binding region and the results revealed MxB-resistant mutations at amino acid
      positions 86, 87, 88 and 92 in capsid. All these mutations diminished the
      interaction of HIV-1 capsid with CypA. CONCLUSIONS: Our results demonstrate the
      existence of MxB-resistant T/F HIV-1 strains. The high prevalence of MxB
      resistant mutations in the CypA-binding loop indicates the significant selective
      pressure of MxB on HIV-1 replication in vivo especially given that this viral
      resistance mechanism operates at expense of losing CypA.

PMID- 25571930
TI  - Cobalt oxide-carbon nanosheet nanoarchitecture as an anode for high-performance
      lithium-ion battery.
AB  - To improve the electrochemical performance of cobalt oxide owing to its inherent
      poor electrical conductivity and large volume expansion/contraction, Co3O4-carbon
      nanosheet hybrid nanoarchitectures were synthesized by a facile and scalable
      chemical process. However, it is still a challenge to control the size of Co3O4
      particles down to ~5 nm. Herein, we created nanosized cobalt oxide anchored 3D
      arrays of carbon nanosheets by the control of calcination condition. The
      uniformly dispersed Co3O4 nanocrystals on carbon nanosheets held a diameter down
      to ~5 nm. When tested as anode materials for lithium-ion batteries, high lithium
      storage over 1200 mAh g(-1) is achieved, whereas high rate capability with
      capacity of about 390 mAh g(-1) at 10 A g(-1) is maintained through nanoscale
      diffusion distances and interconnected porous structure. After 500 cycles, the
      cobalt oxide-carbon nansheets hybrid display a reversible capacity of about 970
      mAh g(-1) at 1 A g(-1). The synergistic effect between nanosized cobalt oxide and
      sheetlike interconnected carbon nanosheets lead to the greatly improved specific
      capacity and the initial Coulombic efficiency of the hybrids. 

PMID- 25571929
TI  - Expression of CCN family members correlates with the clinical features of
      hepatocellular carcinoma.
AB  - Studies have reported that the CCN family of proteins plays an important role in
      stimulating tumorigenesis. However, the relationship between the CCN protein
      family members and the features of hepatocellular carcinoma (HCC) remains
      unclear. The objective of this study was to determine the relationship between
      the expression levels of CCN protein family members and the features of HCC.
      Expression levels of the CCN family of proteins in 80-paired primary HCC samples
      and 11 normal liver samples were determined by a quantitative real-time PCR
      assay. Enhanced expression of nephroblastoma overexpressed protein (NOV) and
      decreased expression of Wnt-induced secreted protein 1 (WISP1), cysteine-rich
      protein 61 (CYR61) and connective tissue growth factor (CTGF) were found in HCC
      samples when compared to levels in matched non-cancerous tissues. No significant
      difference in WISP2 was found between matched-pair samples; only a few samples
      showed WISP3 expression. Furthermore, the expression levels of NOV, WISP1 and
      CYR61 were closely correlated with certain clinical features, including venous
      invasion, cellular differentiation, pTNM stage, disease-free survival and overall
      survival. Our results suggest that HCC progression may be enhanced by NOV and
      suppressed by WISP1 and CYR61. Our statistical analysis suggests that these
      proteins may be valuable in determining the prognosis of this deadly disease and
      directs attention to modulating the levels of these proteins as a potential mode
      of therapy.

PMID- 25571931
TI  - Do elderly patients call 911 when presented with clinical scenarios suggestive of
      acute stroke? A cross-sectional study.
AB  - BACKGROUND AND PURPOSE: Among patients with acute stroke symptoms, delay in
      hospital admission is the main obstacle for the use of thrombolytic therapy and
      other interventions associated with decreased mortality and disability. The
      primary aim of this study was to assess whether an elderly clinical population
      correctly endorsed the response to call for emergency services when presented
      with signs and symptoms of stroke using a standardized questionnaire. METHODS: We
      performed a cross-sectional study among elderly out-patients (>=60 years) in
      Buenos Aires, Argentina randomly recruited from a government funded health
      clinic. The correct endorsement of intention to call 911 was assessed with the
      Stroke Action Test and the cut-off point was set at >=75%. Knowledge of stroke
      and clinical and socio-demographic indicators were also collected and evaluated
      as predictors of correct endorsement using logistic regression. RESULTS: Among
      367 elderly adults, 14% correctly endorsed intention to call 911. Presented with
      the most typical signs and symptoms, only 65% reported that they would call an
      ambulance. Amaurosis Fugax was the symptom for which was called the least (15%).
      On average, the correct response was chosen only 37% of the time. Compared to
      lower levels of education, higher levels were associated to correctly endorsed
      intention to call 911 (secondary School adjusted OR 3.53, 95% CI 1.59-7.86 and
      Tertiary/University adjusted OR 3.04, 95% CI 1.12-8.21). CONCLUSIONS: These
      results suggest the need to provide interventions that are specifically designed
      to increase awareness of potential stroke signs and symptoms and appropriate
      subsequent clinical actions.

PMID- 25571932
TI  - Gabapentin prophylaxis for postoperative nausea and vomiting in abdominal
      surgeries: a quantitative analysis of evidence from randomized controlled
      clinical trials.
AB  - INTRODUCTION: Postoperative nausea and vomiting (PONV) is frequently encountered
      in the surgical recovery room. Abdominal surgery is one important risk factor for
      increased incidence of PONV. Gabapentin, an anticonvulsant with known
      postoperative analgesic properties, has shown some activity against PONV. Results
      from clinical trials evaluating the anti-emetic efficacy of gabapentin are
      conflicting. The present meta-analysis was performed to examine this issue.
      METHODS: Seventeen randomized placebo-controlled trials reporting PONV with
      preoperative gabapentin administration in patients undergoing abdominal surgery
      were included for analysis. Outcomes evaluated were nausea, vomiting, composite
      PONV and the use of rescue anti-emetic medication in the postoperative period.
      RESULTS: The pooled relative risk (RR), estimated using the random effects model
      of the metafor package for R, was 0.76 (95% CI 0.58-0.98) for nausea, 0.62 (0.45
      0.85) for vomiting, 0.71 (0.39-1.28) for data represented as composite PONV
      (possibly biased by a single study, as observed in the sensitivity analysis), and
      0.6 (0.41-0.89) for rescue anti-emetic use. There was a significant RR reduction
      for nausea and vomiting when propofol was not used as induction and/or
      maintenance for anaesthesia. In the abdominal hysterectomy subgroup, there was a
      significant RR reduction for vomiting but not for nausea. DISCUSSION: The present
      analysis provides evidence supporting preoperative gabapentin as a
      pharmacotherapy for prevention of PONV in patients undergoing abdominal
      surgeries. Future studies comparing preoperative gabapentin with 5HT3 antagonists
      are needed to precisely define its role in PONV.

PMID- 25571933
TI  - Learning through simulated independent practice leads to better future
      performance in a simulated crisis than learning through simulated supervised
      practice.
AB  - BACKGROUND: Anaesthetists may fail to recognize and manage certain rare
      intraoperative events. Simulation has been shown to be an effective educational
      adjunct to typical operating room-based education to train for these events. It
      is yet unclear, however, why simulation has any benefit. We hypothesize that
      learners who are allowed to manage a scenario independently and allowed to fail,
      thus causing simulated morbidity, will consequently perform better when re
      exposed to a similar scenario. METHODS: Using a randomized, controlled, observer
      blinded design, 24 first-year residents were exposed to an oxygen pipeline
      contamination scenario, either where patient harm occurred (independent group,
      n=12) or where a simulated attending anaesthetist intervened to prevent harm
      (supervised group, n=12). Residents were brought back 6 months later and exposed
      to a different scenario (pipeline contamination) with the same end point.
      Participants' proper treatment, time to diagnosis, and non-technical skills
      (measured using the Anaesthetists' Non-Technical Skills Checklist, ANTS) were
      measured. RESULTS: No participants provided proper treatment in the initial
      exposure. In the repeat encounter 6 months later, 67% in the independent group vs
      17% in the supervised group resumed adequate oxygen delivery (P=0.013). The
      independent group also had better ANTS scores [median (interquartile range): 42.3
      (31.5-53.1) vs 31.3 (21.6-41), P=0.015]. There was no difference in time to
      treatment if proper management was provided [602 (490-820) vs 610 (420-800) s,
      P=0.79]. CONCLUSIONS: Allowing residents to practise independently in the
      simulation laboratory, and subsequently, allowing them to fail, can be an
      important part of simulation-based learning. This is not feasible in real
      clinical practice but appears to have improved resident performance in this
      study. The purposeful use of independent practice and its potentially negative
      outcomes thus sets simulation-based learning apart from traditional operating
      room learning.

PMID- 25571935
TI  - Aggressive pituitary tumors.
AB  - Pituitary adenomas are common intracranial tumors that are mainly considered as
      benign. Rarely, these tumors can exhibit an aggressive behavior, characterized by
      gross invasion of the surrounding tissues, resistance to conventional treatment
      leading to early and frequent recurrences. Even more rarely, pituitary tumors can
      give rise to cerebrospinal or systemic metastases qualifying as pituitary
      carcinomas according to the latest WHO definition. In the same classification, a
      subset of tumors with relatively distinct histopathological features was
      identified and defined as atypical adenomas designated to follow a more
      aggressive clinical course. This classification, although clinically useful, does
      not provide an accurate correlation between histopathological findings and the
      clinical behavior of these tumors, neither is it adequate to convey the precise
      features of 'aggressive' tumors. Thus, 'aggressive' pituitary adenomas need to be
      properly defined with clinical, radiological, histological and molecular markers
      in order to identify patients at increased risk of early recurrence or subsequent
      tumor progression. At present, no single marker or classification system of
      pituitary tumor aggressiveness exists, and clinically useful information in the
      literature is insufficient to guide diagnostic and therapeutic decisions.
      Treatment of patients with aggressive pituitary tumors is challenging since
      conventional treatments often fail, necessitating multiple surgical procedures
      with additional radiotherapy. Although traditional chemotherapy applied in other
      neuroendocrine tumors has not been shown to be efficacious, newer agents,
      particularly temozolomide, have shown promising results and are currently used
      despite the lack of data from a randomized prospective trial. Molecular targeted
      therapies such as mTOR and epidermal growth factor inhibitors have also been
      applied and might prove to be useful in the management of these patients. In the
      present review, we provide information regarding the epidemiology and clinical,
      histopathological and molecular features of aggressive pituitary tumors using
      recent employed definitions. In addition, we review currently employed
      therapeutic means providing a therapeutic algorithm and highlight the need to
      identify more specific disease-related and prognostic markers and the necessity
      for central registration of these tumors.

PMID- 25571934
TI  - Tranexamic acid for the prevention and treatment of postpartum haemorrhage.
AB  - Postpartum haemorrhage (PPH) is a major cause of maternal mortality, accounting
      for one-quarter of all maternal deaths worldwide. Uterotonics after birth are the
      only intervention that has been shown to be effective for PPH prevention.
      Tranexamic acid (TXA), an antifibrinolytic agent, has therefore been investigated
      as a potentially useful complement to this for both prevention and treatment
      because its hypothesized mechanism of action in PPH supplements that of
      uterotonics and because it has been proved to reduce blood loss in elective
      surgery, bleeding in trauma patients, and menstrual blood loss. This review
      covers evidence from randomized controlled trials (RCTs) for PPH prevention after
      caesarean (n=10) and vaginal (n=2) deliveries and for PPH treatment after vaginal
      delivery (n=1). It discusses its efficacy and side effects overall and in
      relation to the various doses studied for both indications. TXA appears to be a
      promising drug for the prevention and treatment of PPH after both vaginal and
      caesarean delivery. Nevertheless, the current level of evidence supporting its
      efficacy is insufficient, as are the data about its benefit:harm ratio. Large,
      adequately powered multicentre RCTs are required before its widespread use for
      preventing and treating PPH can be recommended.

PMID- 25571937
TI  - Toward instrument-free digital measurements: a three-dimensional microfluidic
      device fabricated in a single sheet of paper by double-sided printing and
      lamination.
AB  - This study demonstrates a simple approach for fabricating a 3D-MUPAD from a
      single sheet of paper by double-sided printing and lamination. First, a wax
      printer prints vertically symmetrical and asymmetrical wax patterns onto a double
      sided paper surface. Then, a laminator melts the printed wax patterns to form
      microfluidic channels in the paper sheet. The vertically symmetrical wax patterns
      form vertical channels when the melted wax patterns make contact with each other.
      The asymmetrical wax patterns form lateral and vertical channels at the cross
      section of the paper when the printed wax patterns are melted to a lower height
      than the thickness of the single sheet of paper. Finally, the two types of wax
      patterns form a 3D microfluidic network to move fluid laterally and vertically in
      the single sheet of paper. This method eliminates major technical hurdles related
      to the complicated and tedious alignment, assembly, bonding, and punching
      process. This 3D-MUPAD can be used in a multiplex digital assay to measure the
      concentration of a target analyte in a sample solution simply by counting the
      number of colored bars at a fixed time. It does not require any external
      instruments to perform digital measurements. Therefore, we expect that this
      approach could be an instrument-free assay format for use in developing
      countries. 

PMID- 25571936
TI  - Role of CXCL10 in cryoglobulinemia.
AB  - Interferon (IFN)-gamma-induced protein 10 (IP-10/CXCL10) and its receptor, C-X-C
      motif receptor 3, appear to contribute to the pathogenesis of hepatitis C virus
      (HCV)-related mixed cryoglobulinaemia (MC) (HCV+MC). The secretion of CXCL10 by
      cluster of differentiation (CD) CD4+, CD8+, and natural killer-T cells is
      dependent on IFN-gamma, which is itself mediated by the interleukin-12 cytokine
      family. Under the influence of IFN-gamma, CXCL10 is secreted by several cell
      types including lymphocytes, hepatocytes, endothelial cells, fibroblasts, etc. In
      tissues, recruited T helper 1 lymphocytes may be responsible for enhanced IFN
      gamma and tumour necrosis factor-alpha production, which in turn stimulates
      CXCL10 secretion from the cells, therefore creating an amplification feedback
      loop, and perpetuating the autoimmune process. High levels of CXCL10 in
      circulation have been found in HCV+MC, especially in patients with clinically
      active vasculitis. Furthermore, HCV+MC patients with autoimmune thyroiditis (AT)
      have higher levels than those without AT. Further studies are needed to
      investigate interactions between chemokines and cytokines in the pathogenesis,
      and to evaluate whether CXCL10 is a novel therapeutic target in HCV-related MC. 

PMID- 25571938
TI  - Successful treatment of cholinergic urticaria with methantheliniumbromide.
AB  - Cholinergic urticaria (CholU) is a frequent and often hard to treat disorder
      characterized by wheal and flare type reactions that occur in response to
      exercise and passive warming. Antihistamines are the first-line treatment, but
      are often not effective. Here, we report a 33-year-old male CholU patient who was
      able to engage in physical activities without suffering any symptoms for several
      hours following the intake of methantheliniumbromide, an anticholinergic agent
      that suppresses sweating. We confirmed this therapeutic response by pulse
      controlled ergometry testing, which showed delayed sweating and markedly delayed
      and reduced whealing after methantheliniumbromide treatment. Our findings suggest
      that CholU patients may benefit from methantheliniumbromide treatment. 

PMID- 25571939
TI  - On the structure of the Nx phase of symmetric dimers: inferences from NMR.
AB  - NMR measurements on a selectively deuterated liquid crystal dimer CB-C9-CB,
      exhibiting two nematic phases, show that the molecules in the lower temperature
      nematic phase, N(X), experience a chiral environment and are ordered about a
      uniformly oriented director throughout the macroscopic sample. The results are
      contrasted with previous interpretations that suggested a twist-bend spatial
      variation of the director. A structural picture is proposed wherein the molecules
      are packed into highly correlated chiral assemblies.

PMID- 25571940
TI  - Synthesis of spiroindanes by palladium-catalyzed oxidative annulation of non- or
      weakly activated 1,3-dienes involving C-H functionalization.
AB  - The synthesis of spiroindanes by the palladium-catalyzed oxidative annulation of
      non- or weakly activated 1,3-dienes with 2-aryl cyclic 1,3-dicarbonyl compounds
      is described. Examples of the dearomatizing oxidative annulation of 1,3-dienes
      with 1-aryl-2-naphthols are also presented. 

PMID- 25571941
TI  - Insights into the bond-selective reaction of Cl + HOD(n(OH)) -> HCl + OD.
AB  - Bond-selective reaction dynamics of the title reaction is investigated using full
      dimensional quantum dynamical (QD) and quasi-classical trajectory (QCT) methods
      on a newly constructed ab initio global potential energy surface. Both QD and QCT
      results indicate that excitation of the local OH vibration in the HOD reactant
      renders the reaction strongly bond selective, with the OD/OH branching ratio in
      quantitative agreement with the experiment. In addition, the reactivity is found
      to be greatly enhanced with the reactant vibrational excitation, thanks to the
      change of a direct rebound mechanism to a capture mechanism. The QCT calculations
      also yield product state distributions, which show that the HCl product is
      vibrationally and rotationally hot while the OD co-product is internally cold.
      The bond selectivity, vibrational enhancement, and product energy disposal are
      rationalized by the Sudden Vector Projection model. 

PMID- 25571942
TI  - A novel rechargeable battery with a magnesium anode, a titanium dioxide cathode,
      and a magnesium borohydride/tetraglyme electrolyte.
AB  - The strong push for electric vehicles and large-scale power storage systems has
      generated intense interest in rechargeable magnesium batteries due to the innate
      merits associated with the magnesium metal anode in terms of volumetric capacity,
      abundance, and operational safety. Herein, we report a novel pathway toward the
      development of an advanced battery containing a magnesium anode, a titanium
      dioxide cathode, and a magnesium borohydride/tetraglyme electrolyte, which
      delivers high specific capacity, as well as exceptional cycle life and rate
      capability. This work demonstrates the importance of compatibility of the
      electrochemical activities of the cathode materials and electrolytes in
      rechargeable Mg batteries. 

PMID- 25571943
TI  - Ethnic differences in associations among popularity, likability, and trajectories
      of adolescents' alcohol use and frequency.
AB  - Two-part latent growth models examined associations between two forms of peer
      status (popularity, likability) and adolescents' alcohol use trajectories
      throughout high school; ethnicity was examined as a moderator. Ninth-grade low
      income adolescents (N = 364; Mage = 15.08; 52.5% Caucasian; 25.8% African
      American; 21.7% Latino) completed sociometric nominations of peer status and
      aggression at baseline, and reported their alcohol use every 6 months. After
      controlling for gender, aggression, ethnicity, and socioeconomic status,
      popularity-but not likability-prospectively predicted alcohol use trajectories.
      However, these effects were moderated by ethnicity, suggesting popularity as a
      risk factor for alcohol use probability and frequency among Caucasian and Latino,
      but not African American adolescents. Results suggest that developmental
      correlates of peer status should be considered within cultural context.

PMID- 25571944
TI  - Constant Hepatitis E Virus (HEV) Circulation in Wild Boar and Red Deer in Spain:
      An Increasing Concern Source of HEV Zoonotic Transmission.
AB  - Hepatitis E is a viral zoonosis that affects multiple hosts. The complete
      dynamics of infection in wildlife are still unknown, but the previous fact
      facilitates the maintenance and circulation of the virus, posing a risk to human
      health in the case of meat consumption from susceptible animals. In Spain, it has
      been shown how domestic pigs, cattle and wildlife (i.e. wild boar and red deer)
      clearly interact in hunting farms, generating a complex epidemiological situation
      in terms of interspecies pathogen transmission. Therefore, in this study, we
      aimed to (i) evaluate the circulation of the virus in geographically close
      domestic (Iberian pigs) and wild animals (wild boar and deer) living in hunting
      areas from central Spain over an 8-year period (2003-2010) and (ii) to determine
      whether HEV could be used as a marker of domestic-wildlife contact. For these
      purposes, a longitudinal analysis of Iberian pig, wild boar and red deer samples
      (n = 287) through virological and serological tests was conducted to shed light
      upon the circulation events of HEV. Regarding HEV RNA detection by real-time RT
      PCR, 10.12% samples (95% CI: 5.44-14.8) from wild boar and 16.05% samples (95%
      CI: 8.06-24.04) from red deer were positive. As for the Iberian pigs, none of the
      48 samples was positive for HEV RNA detection. In the serological analysis,
      43.75% (95% CI: 29.75-57.75) from Iberian pig, 57.40% (95% CI: 48.10-66.70) from
      wild boar and 12.85% (95% CI: 5.01-20.69) samples from red deer presented anti
      HEV antibodies. Positive samples were distributed among all study years (2003
      2010). These results depict the urgent need to improve the inspection and
      surveillance of these species and their products. In the case of HEV, it is clear
      that the stable and constant presence of the virus in wildlife and its contact
      with Iberian pigs pose a risk for human health as they are all destined for human
      consumption. 

PMID- 25571945
TI  - Sex differences in the prevalence of diastolic dysfunction in cardiac surgical
      patients.
AB  - OBJECTIVES: The mortality from diastolic dysfunction is approximately 9% to 28%.
      In patients with ischemic heart disease, female sex and advanced age are
      associated with increases in ventricular diastolic stiffness. Clinical studies
      have found higher rates of diastolic dysfunction in women, despite higher
      ejection fractions, than in men post-myocardial infarction. Therefore, we
      hypothesized that female patients undergoing cardiac surgery have higher degrees
      of diastolic dysfunction and experience more adverse outcomes, such as prolonged
      hospitalization. METHODS: We prospectively enrolled 153 patients undergoing
      cardiac surgery. Diastolic function was assessed using early transmitral velocity
      (E) and early diastolic lateral mitral annular tissue velocity (e'). Left
      ventricular diastolic dysfunction was defined as binary and a continuous outcome
      (E/e'). RESULTS: Females were more likely than males to present with higher E/e'
      (11.5 vs. 7.9, p = 0.001) and higher left ventricular diastolic dysfunction (71%
      vs. 36%, p < 0.001). The addition of sex to the model for left ventricular
      diastolic dysfunction was significant. The relationship between sex and E/e'
      ratio showed the biggest difference between males and females in the 56-72-year
      old age brackets, where women were much more likely to have a higher E/e' than
      males. CONCLUSIONS: We identified a significantly higher prevalence of diastolic
      dysfunction among females presenting for elective cardiac surgery compared to
      males. This finding is more pronounced with age. Additionally, we found that
      female sex is at higher risk of prolonged ICU and hospital length of stay.

PMID- 25571946
TI  - After the genome sequencing of duckweed - how to proceed with research on the
      fastest growing angiosperm?

PMID- 25571947
TI  - The effect of topical treatment with doxycycline compared to saline on 66 avulsed
      permanent teeth--a retrospective case-control study.
AB  - BACKGROUND/AIM: Tooth avulsion in young growing individuals is an uncommon but
      very severe dental trauma. The aim of this retrospective case-control study was
      to evaluate the effect of topical treatment with doxycycline on avulsed permanent
      teeth compared with treatment with only saline regarding pulp survival and
      periodontal healing. MATERIAL AND METHOD: Sixty-six avulsed teeth in 50 patients
      (34 boys and 16 girls) between the ages six and 18 years were included in this
      study. Thirty teeth were soaked in a 0.05 mg ml(-1) doxycycline solution for 5
      min, before replantation and 36 teeth in saline solution. Root development was
      categorized with respect to root formation and development of the apex into three
      groups, one-half-root formation to full root formation with open apex, full root
      formation with half-closed apex and full root formation with closed apex. Pulp
      survival and periodontal healing were assessed as successful when at the end of
      the observation period no pulp necrosis or ankylosis-related resorption was
      diagnosed. The mean observation time was 48 months. RESULTS: In the doxycycline
      group, 27 were diagnosed with pulp necrosis, 15 with ankylosis-related resorption
      and nine were extracted. In the saline group, 30 were diagnosed with pulp
      necrosis, 23 with ankylosis-related resorption and 11 were extracted. Regarding
      pulp survival and periodontal healing, no significant differences were found
      between the two groups. Teeth with immature root development showed significantly
      less pulp necrosis (P < 0.05) compared to teeth with full root formation
      regardless if treated topically with doxycycline or not. No significant
      differences were found between the two groups regarding age, storage, root
      development, splinting duration and observation time although the saline group
      had significantly longer extra-oral time (P < 0.001) than the doxycycline group.
      CONCLUSIONS: This study indicates that avulsed permanent teeth soaked in
      doxycycline do not show a better treatment outcome regarding pulp survival and
      periodontal healing compared with avulsed teeth placed only in saline solution.
      This finding is consistent regardless of root development, storage and extra-oral
      time.

PMID- 25571948
TI  - Last but not least: new insights into how FtsN triggers constriction during
      Escherichia coli cell division.
AB  - The arrival of FtsN at the division site triggers synthesis of septal
      peptidoglycan and constriction of the cell envelope. New findings are changing
      our view of how this happens. Binding of FtsN's cytoplasmic domain to a protein
      named FtsA recruits a small amount of FtsN to the division site earlier than
      previously recognized. The ability of FtsA to interact with FtsN is regulated by
      the ZipA protein. The FtsN-FtsA interaction pushes FtsA into an 'on' conformation
      that activates the machinery for peptidoglycan synthesis. In addition, a small
      region of FtsN's periplasmic domain appears to interact with the FtsQLB complex,
      pushing it into an 'on' state that also triggers synthesis of peptidoglycan.
      Thus, FtsN allosterically activates peptidoglycan synthesis by two pathways, one
      in the cytoplasm and involving FtsA, and the other in the periplasm and involving
      FtsQLB. 

PMID- 25571950
TI  - Functions of the bone morphogenetic protein signaling pathway through microRNAs
      (review).
AB  - MicroRNAs (miRNAs or miRs) have emerged as key regulators of gene expression in
      essential cellular processes, such as cell growth, differentiation and
      development. Recent findings have established that the levels of miRNAs are
      modulated by cell signaling mechanisms, including the bone morphogenetic protein
      (BMP) signaling pathway. The BMP signaling pathway controls diverse cellular
      activities by modulating the levels of miRNAs, indicating the complexity of gene
      regulation by the BMP signaling pathway. The tight regulation of the levels of
      miRNAs is critical for maintaining normal physiological conditions, and
      dysregulated miRNA levels contribute to the development of diseases. In the
      present review, we discuss different insights (provided over the past decade)
      into the regulation of miRNAs governed by the BMP signaling pathway and the
      implications of this regulation on the understanding of the cellular
      differentiation of vascular smooth muscle cells (VSMCs), osteoblasts and neuronal
      cells. 

PMID- 25571949
TI  - Molecular determinants of positive allosteric modulation of the human
      metabotropic glutamate receptor 2.
AB  - BACKGROUND AND PURPOSE: The activation of the metabotropic glutamate receptor 2
      (mGlu2 ) reduces glutamatergic transmission in brain regions where excess
      excitatory signalling is implicated in disorders such as anxiety and
      schizophrenia. Positive allosteric modulators (PAMs) can provide a fine-tuned
      potentiation of these receptors' function and are being investigated as a novel
      therapeutic approach. An extensive set of mutant human mGlu2 receptors were used
      to investigate the molecular determinants that are important for positive
      allosteric modulation at this receptor. EXPERIMENTAL APPROACH: Site-directed
      mutagenesis, binding and functional assays were employed to identify amino acids
      important for the activity of nine PAMs. The data from the radioligand binding
      and mutagenesis studies were used with computational docking to predict a binding
      mode at an mGlu2 receptor model based on the recent structure of the mGlu1
      receptor. KEY RESULTS: New amino acids in TM3 (R635, L639, F643), TM5 (L732) and
      TM6 (W773, F776) were identified for the first time as playing an important role
      in the activity of mGlu2 PAMs. CONCLUSIONS AND IMPLICATIONS: This extensive study
      furthers our understanding of positive allosteric modulation of the mGlu2
      receptor and can contribute to improved future design of mGlu2 PAMs.

PMID- 25571952
TI  - Adenovirus-mediated ING4/PTEN double tumor suppressor gene co-transfer modified
      by RGD enhances antitumor activity in human nasopharyngeal carcinoma cells.
AB  - Inhibitor of growth-4 (ING4) is a member of the inhibitor of growth (ING) family
      and acts as a tumor suppressor protein. PTEN is a phosphatase and shows potent
      and extensive antitumor activity. In this study, we constructed an RGD-modified
      bicistronic ING4/PTEN adenovirus (Ad.RGD-ING4-PTEN) and comprehensively
      investigated its effects following modification of the CNE human nasopharyngeal
      carcinoma cell line both in vitro and in vivo. We demonstrated that Ad.RGD-ING4
      PTEN enhanced growth inhibition and apoptosis. Furthermore, expression of P21,
      Bax and cleaved caspase-3 was upregulated, while that of Bcl-2 and survivin was
      downregulated in CNE cells and CNE xenografted tumors. Moreover, Ad.RGD-ING4-PTEN
      treatment additively downregulated CD34, VEGF and microvessel density in
      subcutaneously (s.c.) xenografted CNE cell tumors. The enhanced antitumor
      activity generated by Ad.RGD-ING4-PTEN was closely associated with activation of
      the intrinsic and extrinsic apoptotic pathways and additive inhibition of tumor
      angiogenesis both in vitro and in vivo. On the basis of this evidence, it is
      believed that cancer gene therapy combining two tumor suppressors such as ING4
      and PTEN can be used to establish an effective and novel therapeutic strategy for
      nasopharyngeal carcinoma and other cancers.

PMID- 25571951
TI  - Effect of small nuclear ribonucleoprotein-associated polypeptide N on the
      proliferation of medulloblastoma cells.
AB  - Spliceosome mutations have been reported in various types of cancer and a number
      of antitumor drugs have been observed to tightly bind to spliceosome components.
      Small nuclear ribonucleoprotein-associated polypeptide N (SNRPN) is a small
      ribonuclear protein and is a key spliceosome constituent. However, the role of
      SNRPN in human medulloblastoma remains unknown. In the present study, the effect
      of SNRPN on cell growth was investigated in vitro using the Daoy human
      medulloblastoma cell line. Lentivirus (Lv)-mediated short hairpin (sh) RNA was
      used to silence SNRPN expression, which was verified by reverse transcription
      quantitative polymerase chain reaction and western blotting. Cell proliferation
      was examined by MTT and colony formation assays. Knockdown of SNRPN markedly
      reduced the proliferation and colony formation ability of Daoy medulloblastoma
      cells. In addition, flow cytometric analysis revealed that the cell cycle
      distribution was altered when the Daoy cells were infected with Lv-shSNRPN. To
      the best of our knowledge, this is the first study to investigate the effect of
      SNRPN on cell proliferation in medulloblastoma. The results indicate that SNRPN
      may be a potential novel target for the development of pharmacological
      therapeutics in human medulloblastoma.

PMID- 25571953
TI  - The efficacy of Mycoplasma gallisepticum K-strain live vaccine in broiler and
      layer chickens.
AB  - The efficacy of a live Mycoplasma gallisepticum (MG) vaccine candidate (K-strain)
      was compared to commercially available vaccines in broiler-type chickens (Trial
      1) and layer-type chickens (Trial 2). In Trial 1, three-week-old broiler-type
      chickens were vaccinated via aerosol with K-strain or an F-strain vaccine. The
      vaccinated chickens and 10 non-vaccinated controls were subsequently challenged
      with virulent R-strain via aerosol at six weeks post vaccination; both K-strain
      and F-strain vaccination resulted in significant protection from air sac and
      tracheal lesions, as well as R-strain colonization (P <= 0.05). In Trial 2,
      commercial layer-type chickens were vaccinated with ts-11 (via eye drop) or K
      strain (via aerosol) at 12 weeks of age. At 25 weeks of age these birds were
      challenged with R-strain via aerosol. The ts-11 and K-strain vaccinated groups
      both had significantly lower air sac lesion scores and a lower prevalence of
      ovarian regression after challenge as compared to non-vaccinated chickens (P <=
      0.05). K-strain vaccination also prevented significant tracheal lesions and R
      strain colonization (P <= 0.05). K-strain shows great potential as a highly
      efficacious live MG vaccine in broiler and layer-type chickens for protection of
      the respiratory and reproductive systems as well as prevention of infection with
      field strains. 

PMID- 25571954
TI  - MicroRNA-135b regulates the stability of PTEN and promotes glycolysis by
      targeting USP13 in human colorectal cancers.
AB  - Dysregulation of microRNAs has been reported to be involved in the progression of
      human colorectal cancers (CRCs). Loss of the adenomatous polyposis coli (APC)
      gene is a common initiating event in CRCs. PTEN inactivation by mutation or
      allelic loss also occurs in CRCs. miR-135b was reported to be upregulated in CRCs
      and its overexpression was due to APC/beta-catenin and PTEN/PI3K pathway
      deregulation. APC was proven to be a target of miR-135b and forms a feedback loop
      with miR-135b. In the present study, we found that ubiquitin-specific peptidase
      13 (USP13) was a target of miR-135b. miR-135b downregulated the expression of
      USP13, and reduced the stability of PTEN. miR-135b promoted cell proliferation
      and glycolysis that could be reversed by the overexpression of USP13 or PTEN.
      Moreover, knockdown of USP13 upregulated the levels of endogenous miR-135b, but
      not those in CRC cells with PTEN mutation. The results showed positive feedback
      loops between miR-135b and PTEN inactivation in CRCs.

PMID- 25571955
TI  - Migration of selected hydrocarbon contaminants into dry pasta packaged in direct
      contact with recycled paperboard.
AB  - This paper deals with the migration of selected hydrocarbon contaminants, namely
      mineral oil hydrocarbons (MOH), diisopropyl naphthalenes (DIPN) and
      polyalphaolefins (PAO) from adhesives into dry semolina and egg pasta packaged in
      direct contact with recycled paperboard. Migration was monitored during its shelf
      life (for up to two years) simulating storage in a supermarket (packs on shelves)
      and conditions preventing exchange with the surrounding environment (packs
      wrapped in aluminium foil). Migration from the secondary packaging (transport
      boxes of corrugated board) was also studied for semolina pasta. After 24 months
      of exposure, semolina pasta stored on shelves reached 3.2 and 0.6 mg kg(-1) of
      MOSH and MOAH, respectively, Migration from the adhesives used to close the boxes
      and from the transport boxes contributed about 30% and 25% of the total
      contamination, respectively. The highest contamination levels (14.5 and 2.0 mg
      kg(-1) of MOSH and MOAH, respectively, after 24 months) were found in egg pasta
      stored on shelves (no adhesives), and seemed due to the highest contribution from
      the external environment.

PMID- 25571957
TI  - Estimating national road crash fatalities using aggregate data.
AB  - Injuries and fatalities from road traffic crashes have emerged a major public
      health challenge in Pakistan. Reliable estimates of road crash fatalities (RCF)
      of a country, is a vital element needed for identification and control of key
      risk factors, road-safety improvement efforts and prioritizing national health.
      Reliability of current annual RCF estimates for Pakistan becomes highly
      questionable due to serious underreporting. This study aimed to predict annual
      RCF for Pakistan using data from World Health Organization and International Road
      Federation sources. An ordinary least square (OLS) regression model that relates
      fatality rate with different explanatory variables was developed. RCF were
      predicted for Pakistan for year 2012 and 2013, and results were compared with
      national police reported estimates. Study results indicated that there is serious
      underreporting of RCF in Pakistan and immediate measures are needed to improve
      the existing road crash recording and reporting system at the national and
      subnational levels. 

PMID- 25571956
TI  - Novel gradient echo sequence-based amide proton transfer magnetic resonance
      imaging in hyperacute cerebral infarction.
AB  - In the progression of ischemia, pH is important and is essential in elucidating
      the association between metabolic disruption, lactate formation, acidosis and
      tissue damage. Chemical exchange-dependent saturation transfer (CEST) imaging can
      be used to detect tissue pH and, in particular, a specific form of CEST magnetic
      resonance imaging (MRI), termed amide proton transfer (APT) MRI, which is
      sensitive to pH and can detect ischemic lesions, even prior to diffusion
      abnormalities. The critical parameter governing the ability of CEST to detect pH
      is the sequence. In the present study, a novel strategy was used, based on the
      gradient echo sequence (GRE), which involved the insertion of a magnetization
      transfer pulse in each repetition time (TR) and minimizing the TR for in vivo APT
      imaging. The proposed GRE-APT MRI method was initially verified using a tissue
      like pH phantom and optimized MRI parameters for APT imaging. In order to assess
      the range of acute cerebral infarction, rats (n=4) were subjected to middle
      cerebral artery occlusion (MCAO) and MRI scanning at 7 telsa (T). Hyperacute
      ischemic tissue damage was characterized using multiparametric imaging
      techniques, including diffusion, APT and T2-Weighted MRI. By using a
      magnetization transfer pulse and minimizing TR, GRE-APT provided high spatial
      resolution and a homogeneous signal, with clearly distinguished cerebral anatomy.
      The GRE-APT and diffusion MRI were significantly correlated with lactate content
      and the area of cerebral infarction in the APT and apparent diffusion coefficient
      (ADC) maps matched consistently during the hyperacute period. In addition,
      compared with the infarction area observed on the ADC MRI map, the APT map
      contained tissue, which had not yet been irreversibly damaged. Therefore, GRE-APT
      MRI waa able to detect ischemic lactic acidosis with sensitivity and
      spatiotemporal resolution, suggesting the potential use of pH MRI as a surrogate
      imaging marker of impaired tissue metabolism for the diagnosis and prognosis of
      hyperacute stroke.

PMID- 25571958
TI  - A new flavonoid from Cudrania cochinchinensis.
AB  - Chemical investigation of the ethanol extract of the roots of Cudrania
      cochinchinensis led to the isolation of a new flavonoid, (6S,12S,13R)-1-methoxy
      cyanomaclurin (1), together with seven known compounds, 1,3,5-trihydroxy-4-(3'
      hydroxy-3'-methylbutyl)xanthone (2), 1,3,6-trihydroxy-4-prenylxanthone (3),
      1,3,6,7-tetrahydroxyxanthone (4), 1,3,5,6-tetrahydroxyxanthone (5), 1,3,6
      trihydroxy-5-methoxyxanthone (6), resveratrol (7) and oxyresveratrol (8). The
      structure of compound 1 was elucidated on the basis of 1D and 2D NMR spectra and
      the HR-ESI-MS data. The absolute stereochemistry was deduced via Rh2(OCOCF3)4
      induced CD and NOESY spectra. 

PMID- 25571959
TI  - A comparative study of surface EMG classification by fuzzy relevance vector
      machine and fuzzy support vector machine.
AB  - We present a multiclass fuzzy relevance vector machine (FRVM) learning mechanism
      and evaluate its performance to classify multiple hand motions using surface
      electromyographic (sEMG) signals. The relevance vector machine (RVM) is a sparse
      Bayesian kernel method which avoids some limitations of the support vector
      machine (SVM). However, RVM still suffers the difficulty of possible
      unclassifiable regions in multiclass problems. We propose two fuzzy membership
      function-based FRVM algorithms to solve such problems, based on experiments
      conducted on seven healthy subjects and two amputees with six hand motions. Two
      feature sets, namely, AR model coefficients and room mean square value (AR-RMS),
      and wavelet transform (WT) features, are extracted from the recorded sEMG
      signals. Fuzzy support vector machine (FSVM) analysis was also conducted for wide
      comparison in terms of accuracy, sparsity, training and testing time, as well as
      the effect of training sample sizes. FRVM yielded comparable classification
      accuracy with dramatically fewer support vectors in comparison with FSVM.
      Furthermore, the processing delay of FRVM was much less than that of FSVM, whilst
      training time of FSVM much faster than FRVM. The results indicate that FRVM
      classifier trained using sufficient samples can achieve comparable generalization
      capability as FSVM with significant sparsity in multi-channel sEMG
      classification, which is more suitable for sEMG-based real-time control
      applications. 

PMID- 25571961
TI  - Implementing new advanced airway management standards in the Hungarian physician
      staffed Helicopter Emergency Medical Service.
AB  - In 2011 the Hungarian Air Ambulance Nonprofit Limited Company introduced a new
      Rapid Sequence Intubation standard operating procedure using a template from
      London's Air Ambulance. This replaced a previous ad-hoc and unsafe prehospital
      advanced airway management practice. It was hoped that this would increase
      clinical standards including internationally comparable results. All Rapid
      Sequence Intubations performed by the units of the Hungarian Air Ambulance under
      the new procedure between June 2011 and November 2013 were reviewed in a
      retrospective database analysis. During this period the air ambulance units
      completed 4880 missions with 433 intubations performed according to the new
      procedure. The rate of intubations that were successful on first attempt was
      95.4% (413), while intubation was successful overall in 99.1% (429) of the cases;
      there was no failed airway. 90 complications were noted with 73 (16.9%) patients.
      Average on scene time was 49 minutes (ranging between: 15-110 minutes). This data
      shows that it is possible to effectively change a system that was in place for
      decades by implementing a new robust system that is based on a good template.

PMID- 25571960
TI  - Selenium status in U.K. pregnant women and its relationship with hypertensive
      conditions of pregnancy.
AB  - Dietary intake/status of the trace mineral Se may affect the risk of developing
      hypertensive conditions of pregnancy, i.e. pre-eclampsia and pregnancy-induced
      hypertension (PE/PIH). In the present study, we evaluated Se status in U.K.
      pregnant women to establish whether pre-pregnant Se status or Se supplementation
      affected the risk of developing PE/PIH. The samples originated from the SPRINT
      (Selenium in PRegnancy INTervention) study that randomised 230 U.K. primiparous
      women to treatment with Se (60 MUg/d) or placebo from 12 weeks of gestation.
      Whole-blood Se concentration was measured at 12 and 35 weeks, toenail Se
      concentration at 16 weeks, plasma selenoprotein P (SEPP1) concentration at 35
      weeks and plasma glutathione peroxidase (GPx3) activity at 12, 20 and 35 weeks.
      Demographic data were collected at baseline. Participants completed a FFQ. U.K.
      pregnant women had whole-blood Se concentration lower than the mid-range of other
      populations, toenail Se concentration considerably lower than U.S. women, GPx3
      activity considerably lower than U.S. and Australian pregnant women, and low
      baseline SEPP1 concentration (median 3.00, range 0.90-5.80 mg/l). Maternal age,
      education and social class were positively associated with Se status. After
      adjustment, whole-blood Se concentration was higher in women consuming Brazil
      nuts (P= 0.040) and in those consuming more than two seafood portions per week
      (P= 0.054). A stepwise logistic regression model revealed that among the Se
      related risk factors, only toenail Se (OR 0.38, 95% CI 0.17, 0.87, P= 0.021)
      significantly affected the OR for PE/PIH. On excluding non-compliers with Se
      treatment, Se supplementation also significantly reduced the OR for PE/PIH (OR
      0.30, 95% CI 0.09, 1.00, P= 0.049). In conclusion, U.K. women have low Se status
      that increases their risk of developing PE/PIH. Therefore, U.K. women of
      childbearing age need to improve their Se status.

PMID- 25571962
TI  - Epidemiology of amyotrophic lateral sclerosis and effect of riluzole on disease
      course.
AB  - OBJECTIVES: To assess the epidemiology of ALS in Austria and to evaluate the long
      term effect of riluzole treatment on survival. METHODS: Hospital discharge and
      riluzole prescription databases were used to identify ALS cases from January 2008
      to June 2012. Using the capture-recapture method we evaluated the incidence and
      prevalence of ALS and patients' survival in dependence of age, gender and
      riluzole treatment. RESULTS: The corrected incidence and prevalence of ALS were
      3.13/100,000 person-years (95% CI, 2.77 to 3.50) and 9.14/100,000 persons (95%
      CI, 8.53 to 9.79), respectively. Median survival from diagnosis was 676 days (95%
      CI, 591 to 761). A younger age at diagnosis was associated with a longer
      survival. Gender did not appear to affect survival time. Riluzole therapy was
      associated with a survival advantage only for the initial treatment period. The
      adjusted hazard ratio of mortality for using riluzole increased continually over
      time resulting in an apparent reversal of its beneficial effect after 6 months of
      therapy. CONCLUSIONS: We report incidence and prevalence estimates that are on
      the upper end of the wide range discussed in literature. Riluzole seems to exert
      a beneficial effect only in the first 6 months of therapy.

PMID- 25571963
TI  - Weill-Marchesani syndrome with advanced glaucoma and corneal endothelial
      dysfunction: a case report and literature review.
AB  - BACKGROUND: To report the diagnostic features and management strategy of a rare
      case of Weill-Marchesani syndrome with advanced glaucoma and corneal endothelial
      dysfunction. CASE PRESENTATION: A patient presented with advanced glaucoma with
      an intraocular pressure of 49 mmHg in the left eye, and subsequently received
      trabeculectomy to control the intraocular pressure. Surprisingly, slit lamp
      examination through the dilated pupil revealed a dislocated microspherophakic
      lens almost touching the corneal endothelium. A microspherophakic lens was
      confirmed by anterior segment optical coherence tomography. Weill-Marchesani
      syndrome was then diagnosed by ocular examinations, and was accompanied by
      systemic abnormalities, including brachymorphia and brachydactyly. Corneal
      endothelial microscopy showed severe corneal endothelial dysfunction, and lens
      extraction and intraocular lens implantation were subsequently performed to
      prevent further endothelial damage. At the 1-year follow-up visit, the patient
      had well-controlled intraocular pressure, transparent cornea, and normal anterior
      chamber depth, while the intraocular lens remained correctly in place.
      CONCLUSIONS: Weill-Marchesani syndrome could be diagnosed by microspherophakia,
      high myopia, secondary glaucoma, and systemic abnormalities such as brachymorphia
      and brachydactyly. Removal of the microspherophakia is recommended to control
      intraocular pressure and improve vision. Advanced glaucoma in Weill-Marchesani
      syndrome should be treated with combined glaucoma surgery and lens extraction.

PMID- 25571964
TI  - STAT3 regulates the migration and invasion of a stem-like subpopulation through
      microRNA-21 and multiple targets in hepatocellular carcinoma.
AB  - Despite advances in the detection and treatment of hepatocellular carcinoma
      (HCC), the prognosis remains poor partly due to recurrence or extra/intrahepatic
      metastasis. Stem-like cancer cells are considered the source of malignant
      phenotypes including metastasis in various types of cancer. HCC side population
      (SP), considered as stem-like cancer cells, plays an important role in the
      migration and invasion in HCC, while the mechanisms involved remain unknown. In
      the present study, high levels of STAT3 and phospho-STAT3 were observed in
      MHCC97H SP cells compared with the main population (MP) cells. Inhibition of
      phospho-STAT3 led to a reduction of miR-21 expression, an increase of PTEN, RECK,
      and programmed cell death 4 (PDCD4) expression as well as the migration and
      invasion of SP cells. A set of rescue experiments was performed using different
      combinations of STAT3 inhibitor, miR-21 mimics and siRNAs to observe the
      expression of miR-21 targets, cell migration and invasion alterations. Data
      indicated that the alterations induced by STAT3 inhibition were partly reversed
      by the upregulation of miR-21. Additionally, the cells migration and invasion
      when silencing the targets of miR-21 were also reversed by STAT3 inhibition. In
      conclusion, the present study revealed the aberrant expression of STAT3 and miR
      21 in HCC SP cells. Targeting STAT3 may limit HCC migration and invasion, which
      is likely to involve the regulation of miR-21 and its targets PTEN, RECK and
      PDCD4. Strategies directed towards STAT3 may therefore be a novel approach for
      the treatment of HCC. 

PMID- 25571965
TI  - Sets of medians in the non-geodesic pseudometric space of unsigned genomes with
      breakpoints.
AB  - BACKGROUND: The breakpoint median in the set Sn of permutations on n terms is
      known to have some unusual behavior, especially if the input genomes are
      maximally different to each other. The mathematical study of the set of medians
      is complicated by the facts that breakpoint distance is not a metric but a pseudo
      metric, and that it does not define a geodesic space. RESULTS: We introduce the
      notion of partial geodesic, or geodesic patch between two permutations, and show
      that if two permutations are medians, then every permutation on a geodesic patch
      between them is also a median. We also prove the conjecture that the input
      permutations themselves are medians.

PMID- 25571966
TI  - Development and preliminary evaluation of a rehabilitation consult for survivors
      of head and neck cancer: an intervention mapping protocol.
AB  - BACKGROUND: Evidence suggests that rehabilitation interventions can improve
      function and quality of life in survivors of head and neck cancer (HNC), but
      there is a lack of coordinated, integrated services, and those offered are
      inconsistent. To address these gaps, we will develop and conduct preliminary
      evaluation of a rehabilitation consult, built on the theoretical foundations of
      goal setting and self-management, and composed of a brief functional evaluation,
      a resource compendium, and collaborative goal-setting and action planning
      processes. METHODS/DESIGN: The development of the rehabilitation consult will be
      guided by intervention mapping, which consists of six steps: 1. Needs assessment;
      2. Definition of program objectives; 3. Selection of theory-based intervention
      methods; 4. Production and pretesting; 5. Adoption, implementation and
      sustainability planning; 6. Process and effect evaluation. Within the
      intervention mapping framework, an iterative process of constructing drafts and
      mini-evaluations with consumers and experts will be used, modifying the
      rehabilitation consult intervention until a version suitable for formal
      evaluation is established. The rehabilitation consult will then be evaluated
      using a prospective, mixed method, single group design with 30 survivors of head
      and neck cancer. Outcomes will be assessed pre- and post-intervention and at 6
      month follow-up. DISCUSSION: Survivors of head and neck cancer have among the
      most complex rehabilitation needs of all cancer patients. The rehabilitation
      consult is expected to improve knowledge and uptake of rehabilitation resources
      and strategies in survivors of head and neck cancer and thereby improve long-term
      function and quality of life. If the rehabilitation consult is effective in
      cancer patients with such high and diverse needs, this project will produce a
      toolkit that will be adaptable for other types of cancer in other jurisdictions.

PMID- 25571967
TI  - Clinical relevance of studies on the accuracy of visual inspection for detecting
      caries lesions: a systematic review.
AB  - Although visual inspection is the most commonly used method for caries detection,
      and consequently the most investigated, studies have not been concerned about the
      clinical relevance of this procedure. Therefore, we conducted a systematic review
      in order to perform a critical evaluation considering the clinical relevance and
      methodological quality of studies on the accuracy of visual inspection for
      assessing caries lesions. Two independent reviewers searched several databases
      through July 2013 to identify papers/articles published in English. Other sources
      were checked to identify unpublished literature. The eligible studies were those
      which (1) assessed the accuracy of the visual method for detecting caries lesions
      on occlusal, approximal or smooth surfaces, in primary or permanent teeth, (2)
      used a reference standard, and (3) reported data about sample size and accuracy
      of the methods. Aspects related to clinical relevance and the methodological
      quality of the studies were evaluated. 96 of the 5,578 articles initially
      identified met the inclusion criteria. In general, most studies failed in
      considering some clinically relevant aspects: only 1 included study validated
      activity status of lesions, no study considered its prognosis, 79 studies did not
      consider a clinically relevant outcome, and only 1 evaluated a patient-centred
      outcome. Concerning methodological quality, the majority of the studies presented
      a high risk of bias in sample selection. In conclusion, studies on the accuracy
      of the visual method for caries detection should consider clinically relevant
      outcomes besides accuracy; moreover, they should be conducted with higher
      methodological quality, mainly regarding sample selection.

PMID- 25571968
TI  - Urinary glucocorticoid metabolites: biomarkers to classify adrenal
      incidentalomas?
AB  - OBJECTIVE: Total urinary cortisol metabolites represent cortisol production and
      metabolism. We hypothesized that to assay metabolites could add some information
      to the one provided by a sole cortisol assay. DESIGN AND PATIENTS: We set up an
      inexpensive multiplex mass spectrometry assay to quantify cortisol metabolites.
      We investigated 43 patients with benign secreting (AT+) or silent (AT-) adrenal
      tumours compared to 48 lean (Nl) or 143 obese (Ob) subjects, and to 26 patients
      with a Cushing's disease (CD). The initial investigation included immunoreactive
      quantification of urinary free cortisol (UFC). RESULTS: Cortisol metabolites were
      overexcreted in CD but not in Ob subjects. Nl and Ob were thus pooled in a
      control population (Ctl). Cortisol, tetrahydrocortisol (THF) and
      tetrahydrocortisone (THE) excretions were significantly increased in AT compared
      to Ctl subjects, whereas immunoreactive UFC was similar. A logistic regression
      retaining cortisol, THF, and alpha- and beta-cortolone as significant analytes
      allowed the construction of a receiver-operating characteristics (ROC) curve
      significantly better than the curve generated by cortisol alone (area under the
      curve (AUC) 0.927 vs 0.729, respectively; P < 0.0001). More importantly, although
      there was no significant difference between Ctl vs AT- subjects for cortisol
      metabolites, a logistic regression retaining cortisol, allo-THF, and alpha- and
      beta-cortolone as significant analytes generated a ROC curve performing
      significantly better than cortisol alone (AUC 0.910 vs 0.635, respectively; P <
      0.0001). CONCLUSION: Cortisol metabolite excretion is modified in AT, including
      AT-, patients even without modification of UFC. Clinical usefulness of these
      biomarkers has to be investigated in prospective studies following up patients
      with AT.

PMID- 25571969
TI  - Seasonality of birth of patients with juvenile idiopathic arthritis.
AB  - OBJECTIVES: The aim of this study was to determine the seasonality of month of
      birth (MOB) in children with juvenile idiopathic arthritis (JIA) as compared to
      the general population. METHODS: Cosinor analysis was used to analyse MOB
      rhythmicity in 558 children with JIA from a simple rheumatology clinic compared
      with the MOB pattern of the general population in Israel (n=1.040558).
      Statistical differences between groups were also analysed by non-parametrical
      tests. RESULTS: Patients with JIA showed different patterns from that of the
      general population. A rhythmic pattern of 12 months was found in the MOB patterns
      of JIA patients. This rhythm with a peak between November to March and a nadir in
      summer was a mirror image of the rhythmic pattern observed for MOB of the healthy
      population. Males showed a pattern with combined rhythm of 8 and 6 months with
      peaks in winter, while females' MOB pattern showed no rhythmicity. Testing
      different JIA subtypes, only the patients with the enthesitis-related arthritis
      (ERA) subtype showed rhythmicity in MOB. Rhythmicity patterns were different for
      males and females, and differed according to several disease characteristics.
      CONCLUSIONS: The observed pattern of MOB in JIA patients is distinctive and
      different from that in the healthy population supporting the hypothesis that
      autoimmune process may begin in utero or in the perinatal period due to seasonal
      environmental pathogenic agents.

PMID- 25571971
TI  - Hyperacute graft-versus-host disease after bone marrow transplantation for
      mycosis fungoides.

PMID- 25571970
TI  - Isogambogenic acid induces apoptosis-independent autophagic cell death in human
      non-small-cell lung carcinoma cells.
AB  - To overcome drug resistance caused by apoptosis deficiency in patients with non
      small cell lung carcinoma (NSCLC), there is a need to identify other means of
      triggering apoptosis-independent cancer cell death. We are the first to report
      that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic
      cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC
      cells indicated that iso-GNA induced autophagic cell death. First, there was no
      evidence of apoptosis or cleaved caspase 3 accumulation and activation. Second,
      iso-GNA treatment induced the formation of autophagic vacuoles, increased LC3
      conversion, caused the appearance of autophagosomes and increased the expression
      of autophagy-related proteins. These findings provide evidence that iso-GNA
      induces autophagy in NSCLC cells. Third, iso-GNA-induced cell death was inhibited
      by autophagic inhibitors or by selective ablation of Atg7 and Beclin 1 genes.
      Furthermore, the mTOR inhibitor rapamycin increased iso-GNA-induced cell death by
      enhancing autophagy. Finally, a xenograft model provided additional evidence that
      iso-GNA exhibited anticancer effect through inducing autophagy-dependent cell
      death in NSCLC cells. Taken together, our results demonstrated that iso-GNA
      exhibited an anticancer effect by inducing autophagy-dependent cell death in
      NSCLC cells, which may be an effective chemotherapeutic agent that can be used
      against NSCLC in a clinical setting. 

PMID- 25571973
TI  - p73 is required for endothelial cell differentiation, migration and the formation
      of vascular networks regulating VEGF and TGFbeta signaling.
AB  - Vasculogenesis, the establishment of the vascular plexus and angiogenesis,
      branching of new vessels from the preexisting vasculature, involves coordinated
      endothelial differentiation, proliferation and migration. Disturbances in these
      coordinated processes may accompany diseases such as cancer. We hypothesized that
      the p53 family member p73, which regulates cell differentiation in several
      contexts, may be important in vascular development. We demonstrate that p73
      deficiency perturbed vascular development in the mouse retina, decreasing
      vascular branching, density and stability. Furthermore, p73 deficiency could
      affect non endothelial cells (ECs) resulting in reduced in vivo proangiogenic
      milieu. Moreover, p73 functional inhibition, as well as p73 deficiency, hindered
      vessel sprouting, tubulogenesis and the assembly of vascular structures in mouse
      embryonic stem cell and induced pluripotent stem cell cultures. Therefore, p73 is
      necessary for EC biology and vasculogenesis and, in particular, that DNp73
      regulates EC migration and tube formation capacity by regulation of expression of
      pro-angiogenic factors such as transforming growth factor-beta and vascular
      endothelial growth factors. DNp73 expression is upregulated in the tumor
      environment, resulting in enhanced angiogenic potential of B16-F10 melanoma
      cells. Our results demonstrate, by the first time, that differential p73-isoform
      regulation is necessary for physiological vasculogenesis and angiogenesis and
      DNp73 overexpression becomes a positive advantage for tumor progression due to
      its pro-angiogenic capacity. 

PMID- 25571972
TI  - Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells
      but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells
      for apoptotic cell death.
AB  - Tissue damage due to apoptotic or necrotic cell death typically initiates
      distinct cellular responses, leading either directly to tissue repair and
      regeneration or to immunological processes first, to clear the site, for example,
      of potentially damage-inducing agents. Mesenchymal stem cells (MSC) as well as
      immature dendritic cells (iDC) and monocytes migrate to injured tissues. MSC have
      regenerative capacity, whereas monocytes and iDC have a critical role in
      inflammation and induction of immune responses, including autoimmunity after
      tissue damage. Here, we investigated the influence of apoptotic and necrotic cell
      death on recruitment of MSC, monocytes and iDC, and identified hepatocyte growth
      factor (HGF) and the alarmin high mobility group box 1 (HMGB1) as key factors
      differentially regulating these migratory responses. MSC, but not monocytes or
      iDC, were attracted by apoptotic cardiomyocytic and neuronal cells, whereas
      necrosis induced migration of monocytes and iDC, but not of MSC. Only apoptotic
      cell death resulted in HGF production and HGF-mediated migration of MSC towards
      the apoptotic targets. In contrast, HMGB1 was predominantly released by the
      necrotic cells and mediated recruitment of monocytes and iDC via the receptor of
      advanced glycation end products. Moreover, necrotic cardiomyocytic and neuronal
      cells caused an HMGB1/toll-like receptor-4-dependent inhibition of MSC migration
      towards apoptosis or HGF, while recruitment of monocytes and iDC by necrosis or
      HMGB1 was not affected by apoptotic cells or HGF. Thus, the type of cell death
      differentially regulates recruitment of either MSC or monocytes and iDC through
      HGF and HMGB1, respectively, with a dominant, HMGB1-mediated role of necrosis in
      determining tropism after tissue injury. 

PMID- 25571975
TI  - Autophagy supports survival and phototransduction protein levels in rod
      photoreceptors.
AB  - Damage and loss of the postmitotic photoreceptors is a leading cause of blindness
      in many diseases of the eye. Although the mechanisms of photoreceptor death have
      been extensively studied, few studies have addressed mechanisms that help sustain
      these non-replicating neurons for the life of an organism. Autophagy is an
      intracellular pathway where cytoplasmic constituents are delivered to the
      lysosomal pathway for degradation. It is not only a major pathway activated in
      response to cellular stress, but is also important for cytoplasmic turnover and
      to supply the structural and energy needs of cells. We examined the importance of
      autophagy in photoreceptors by deleting the essential autophagy gene Atg5
      specifically in rods. Loss of autophagy led to progressive degeneration of rod
      photoreceptors beginning at 8 weeks of age such that by 44 weeks few rods
      remained. Cone photoreceptor numbers were only slightly diminished following rod
      degeneration but their function was significantly decreased. Rod cell death was
      apoptotic but was not dependent on daily light exposure or accelerated by intense
      light. Although the light-regulated translocation of the phototransduction
      proteins arrestin and transducin were unaffected in rods lacking autophagy, Atg5
      deficient rods accumulated transducin-alpha as they degenerated suggesting
      autophagy might regulate the level of this protein. This was confirmed when the
      light-induced decrease in transducin was abolished in Atg5-deficient rods and the
      inhibition of autophagy in retinal explants cultures prevented its degradation.
      These results demonstrate that basal autophagy is essential to the long-term
      health of rod photoreceptors and a critical process for maintaining optimal
      levels of the phototransduction protein transducin-alpha. As the lack of
      autophagy is associated with retinal degeneration and altered phototransduction
      protein degradation in the absence of harmful gene products, this process may be
      a viable therapeutic target where rod cell loss is the primary pathologic event. 

PMID- 25571974
TI  - JSAP1/JIP3 and JLP regulate kinesin-1-dependent axonal transport to prevent
      neuronal degeneration.
AB  - Axonal transport is critical for neuronal development and function, and defective
      axonal transport has been implicated in neurodegenerative diseases. However, how
      axonal transport is regulated, or how defective transport leads to neuronal
      degeneration, remains unclear. Here, we report that c-Jun NH2-terminal kinase
      (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as
      JNK-interacting protein 3 (JIP3)) and JNK-associated leucine zipper protein (JLP)
      are essential for postnatal brain development. Mice with a double-knockout (dKO)
      in Jsap1 and Jlp in the dorsal telencephalon developed progressive neuron loss.
      Using a primary neuron culture system with induced disruption of targeted genes,
      combined with gene rescue experiments, we show that JSAP1 and JLP regulate
      kinesin-1-dependent axonal transport with functional redundancy. We also show
      that the binding of JSAP1 and JLP to kinesin-1 heavy chain is crucial for
      interactions between kinesin-1 and microtubules. Furthermore, we describe a
      molecular mechanism by which defective kinesin-1-dependent axonal transport in
      Jsap1:Jlp dKO neurons causes axonal degeneration and subsequent neuronal death.
      JNK hyperactivation because of increased intra-axonal Ca(2+) in the Jsap1:Jlp dKO
      neurons was found to mediate both the axonal degeneration and neuronal death, in
      cooperation with the Ca(2+)-dependent protease calpain. Our results indicate that
      axonal JNK may relocate to the nucleus in a dynein-dependent manner, where it
      activates the transcription factor c-Jun, resulting in neuronal death. Taken
      together, our data establish JSAP1 and JLP as positive regulators of kinesin-1
      dependent axonal transport, which prevents neuronal degeneration. 

PMID- 25571976
TI  - Phosphatidylethanolamine positively regulates autophagy and longevity.
AB  - Autophagy is a cellular recycling program that retards ageing by efficiently
      eliminating damaged and potentially harmful organelles and intracellular protein
      aggregates. Here, we show that the abundance of phosphatidylethanolamine (PE)
      positively regulates autophagy. Reduction of intracellular PE levels by knocking
      out either of the two yeast phosphatidylserine decarboxylases (PSD) accelerated
      chronological ageing-associated production of reactive oxygen species and death.
      Conversely, the artificial increase of intracellular PE levels, by provision of
      its precursor ethanolamine or by overexpression of the PE-generating enzyme Psd1,
      significantly increased autophagic flux, both in yeast and in mammalian cell
      culture. Importantly administration of ethanolamine was sufficient to extend the
      lifespan of yeast (Saccharomyces cerevisiae), mammalian cells (U2OS, H4) and
      flies (Drosophila melanogaster). We thus postulate that the availability of PE
      may constitute a bottleneck for functional autophagy and that organismal life or
      healthspan could be positively influenced by the consumption of ethanolamine-rich
      food. 

PMID- 25571977
TI  - Transfer of mitochondria via tunneling nanotubes rescues apoptotic PC12 cells.
AB  - Tunneling nanotubes (TNTs) are F-actin-based membrane tubes that form between
      cells in culture and in tissues. They mediate intercellular communication ranging
      from electrical signalling to the transfer of organelles. Here, we studied the
      role of TNTs in the interaction between apoptotic and healthy cells. We found
      that pheochromocytoma (PC) 12 cells treated with ultraviolet light (UV) were
      rescued when cocultured with untreated PC12 cells. UV-treated cells formed a
      different type of TNT with untreated PC12 cells, which was characterized by
      continuous microtubule localized inside these TNTs. The dynamic behaviour of
      mCherry-tagged end-binding protein 3 and the accumulation of detyrosinated
      tubulin in these TNTs indicate that they are regulated structures. In addition,
      these TNTs show different biophysical properties, for example, increased diameter
      allowing dye entry, prolonged lifetime and decreased membrane fluidity. Further
      studies demonstrated that microtubule-containing TNTs were formed by stressed
      cells, which had lost cytochrome c but did not enter into the execution phase of
      apoptosis characterized by caspase-3 activation. Moreover, mitochondria
      colocalized with microtubules in TNTs and transited along these structures from
      healthy to stressed cells. Importantly, impaired formation of TNTs and untreated
      cells carrying defective mitochondria were unable to rescue UV-treated cells in
      the coculture. We conclude that TNT-mediated transfer of functional mitochondria
      reverse stressed cells in the early stages of apoptosis. This provides new
      insights into the survival mechanisms of damaged cells in a multicellular
      context. 

PMID- 25571979
TI  - A minimized designer protein for facile biofabrication of ZnS:Mn immuno-quantum
      dots.
AB  - A minimized protein consisting of a linear ZnS-binding peptide fused to an
      antibody-binding domain supports the one-step aqueous synthesis of Mn-doped ZnS
      nanocrystals that exhibit smaller size, brighter fluorescence and improved
      antibody-binding relative to those made with the original designer protein. 

PMID- 25571980
TI  - The (99m)Tc-DTPA urinary clearance method may be preferable to the plasma
      disappearance method for assessing glomerular filtration rate in diabetic
      nephropathy.
AB  - BACKGROUND: Isotopic glomerular filtration rate (iGFR) measurement is comparable
      to the inulin method. In this study, we compared urinary and plasma iGFR
      methodologies in patients with diabetic nephropathy. METHODS: A total of 147
      patients from 3 sites in the Diabetic Intervention with Vitamins to Improve
      Nephropathy (DIVINe) trial provided 213 sets of urine and blood collections, at
      baseline, 18 and 36 months. RESULTS: The mean (with standard deviation) plasma
      iGFR of 60.7 (24.9) ml/min/1.73 m(2) compared to urinary iGFR of 52.0 (28.0)
      ml/min/1.73 m(2) was statistically significant (p value <0.001). Although plasma
      and urinary iGFRs were highly related (R(2) = 0.86), plasma iGFR increasingly
      overestimated urinary iGFRs at lower GFRs. In contrast to the cross-sectional
      analyses, the two measures of iGFR were weakly related (R(2) = 0.32) in regard to
      patients' change over 18 months of follow-up. CONCLUSION: Plasma iGFR may not be
      a suitable method for accurately measuring GFR in patients with advancing degrees
      of chronic kidney disease from diabetic nephropathy.

PMID- 25571981
TI  - Efficacy of surgical transversus abdominis plane block for postoperative pain
      relief following abdominal surgery in pediatric patients.
AB  - BACKGROUND: Transversus abdominis plane (TAP) block is a promising effective
      method for postoperative pain control after major abdominal surgery. Using a
      landmark technique, it is easily performed, but its popularity has decreased
      because of less efficacy due to inaccurate injection and the potential for
      intraperitoneal organ damage. Ultrasound-guided TAP block provides better results
      and less complications, but it requires experienced operators. Surgically
      administered TAP (sTAP) block is a simple technique and may cause less
      complications. This study was aimed to determine the efficacy of sTAP on
      postoperative pain control in pediatric patients following a major abdominal
      surgery, compared with local anesthetic infiltration and no block. METHODS: This
      stratified, randomized controlled trial was conducted in pediatric patients,
      below the age of 15 years, who underwent non-laparoscopic major abdominal
      surgery. Patients were allocated into three groups. The control group received no
      block; the LA group received 0.25% bupivacaine for local wound infiltration; and
      the sTAP group received 0.25% bupivacaine for TAP block performed by a surgeon
      before abdominal wall closure. Parameter records included the incidence of
      inadequate pain control, time to first analgesic, opioid requirement within 24 h,
      and complications of these techniques. RESULTS: Fifty-four patients were
      recruited. There was no significant difference in the incidence of inadequate
      pain control (P = 0.589). The median time to first analgesic was 380 min in the
      sTAP group compared with 370 and 420 min in the LA and control groups,
      respectively (95%CI = 193-567, 121-619, and 0-1012; P = 0.632). The median dose
      of total opioid requirement (calculated as fentanyl-equivalent dose) was 1.95,
      2.05, and 2.04 MUg.kg(-1) .24 h(-1) in the sTAP, LA, and control groups,
      respectively (IQR = 0.65, 2.20; 0.59, 3.32; 0.38, 2.60; P = 0.723). No
      complications of sTAP block were detected. CONCLUSIONS: There was no significant
      advantage of the sTAP block over local infiltration or no intervention for
      postoperative pain control in pediatric patients undergoing non-laparoscopic
      major abdominal surgeries.

PMID- 25571982
TI  - A CuS-based chemical tongue chip for pattern recognition of proteins and
      antibiotic-resistant bacteria.
AB  - In this work, we developed a CuS-based sensor array having high stability and
      selectivity for complex protein analytes on a quartz chip. Our platform also
      exhibited excellent discrimination ability for the complex analytes of real
      biological samples such as bacteria extracts. 

PMID- 25571983
TI  - A long-term oxidation barrier for copper nanowires: graphene says yes.
AB  - Copper nanowires (Cu NWs) hold great promise for the fabrication of low-cost
      transparent electrodes. However, the instability of Cu NWs has limited their
      application into commercial devices. Herein, CVD-grown graphene is transferred
      onto Cu NW films and the stability of the hybrid films over long time scale under
      different conditions is investigated systematically. The results reveal that the
      graphene-Cu NW films can maintain their efficacy (R/R0 < 2) after 180 days of
      exposure in an ambient atmosphere. Furthermore, a two-step oxidation kinetic
      mechanism of Cu NWs can be proposed by using Raman and X-Ray photoelectron
      spectroscopy. The protecting mechanism of graphene on Cu NW films is disclosed to
      preventing the oxygen species permeation, decelerating the oxidation from Cu to
      Cu2O and hindering the oxidation of Cu2O to CuO. These results are of referring
      significance to make metal nanowire based transparent electrodes with both high
      optical-electrical performance and excellent stability. 

PMID- 25571978
TI  - Biological targets and mechanisms of action of natural products from marine
      cyanobacteria.
AB  - Marine cyanobacteria are an ancient group of organisms and prolific producers of
      bioactive secondary metabolites. These compounds are presumably optimized by
      evolution over billions of years to exert high affinity for their intended
      biological target in the ecologically relevant organism but likely also possess
      activity in different biological contexts such as human cells. Screening of
      marine cyanobacterial extracts for bioactive natural products has largely focused
      on cancer cell viability; however, diversification of the screening platform led
      to the characterization of many new bioactive compounds. Targets of compounds
      have oftentimes been elusive if the compounds were discovered through phenotypic
      assays. Over the past few years, technology has advanced to determine mechanism
      of action (MOA) and targets through reverse chemical genetic and proteomic
      approaches, which has been applied to certain cyanobacterial compounds and will
      be discussed in this review. Some cyanobacterial molecules are the most-potent-in
      class inhibitors and therefore may become valuable tools for chemical biology to
      probe protein function but also be templates for novel drugs, assuming in vitro
      potency translates into cellular and in vivo activity. Our review will focus on
      compounds for which the direct targets have been deciphered or which were found
      to target a novel pathway, and link them to disease states where target
      modulation may be beneficial.

PMID- 25571985
TI  - Assembly of jammed colloidal shells onto micron-sized bubbles by ultrasound.
AB  - Stabilization of gas bubbles in water by applying solid particles is a promising
      technique to ensure long-term stability of the dispersion against coarsening.
      However, the production of large quantities of particle stabilized bubbles is
      challenging. The delivery of particles to the interface must occur rapidly
      compared to the typical time scale of coarsening during production. Furthermore,
      the production route must be able to overcome the energy barriers for interfacial
      adsorption of particles. Here we demonstrate that ultrasound can be applied to
      agitate a colloidal dispersion and supply sufficient energy to ensure particle
      adsorption onto the air-water interface. With this technique we are able to
      produce micron-sized bubbles, solely stabilized by particles. The interface of
      these bubbles is characterized by a colloidal shell, a monolayer of particles
      which adopt a hexagonal packing. The particles are anchored to the interface
      owing to partial wetting and experience lateral compression due to bubble
      shrinkage. The combination of both effects stops coarsening once the interface is
      jammed with particles. As a result, stable bubbles are formed. Individual
      particles can desorb from the interface upon surfactant addition, though. The
      latter fact confirms that the particle shell is not covalently linked due to
      thermal sintering, but is solely held together by capillary interaction. In
      summary, we show that our ultrasound approach allows for the straightforward
      creation of micron-sized particle stabilized bubbles with high stability towards
      coarsening. 

PMID- 25571984
TI  - Rational targeting of active-site tyrosine residues using sulfonyl fluoride
      probes.
AB  - This work describes the first rational targeting of tyrosine residues in a
      protein binding site by small-molecule covalent probes. Specific tyrosine
      residues in the active site of the mRNA-decapping scavenger enzyme DcpS were
      modified using reactive sulfonyl fluoride covalent inhibitors. Structure-based
      molecular design was used to create an alkyne-tagged probe bearing the sulfonyl
      fluoride warhead, thus enabling the efficient capture of the protein from a
      complex proteome. Use of the probe in competition experiments with a
      diaminoquinazoline DcpS inhibitor permitted the quantification of intracellular
      target occupancy. As a result, diaminoquinazoline upregulators of survival motor
      neuron protein that are used for the treatment of spinal muscular atrophy were
      confirmed as inhibitors of DcpS in human primary cells. This work illustrates the
      utility of sulfonyl fluoride probes designed to react with specific tyrosine
      residues of a protein and augments the chemical biology toolkit by these probes
      uses in target validation and molecular pharmacology. 

PMID- 25571986
TI  - Hospital crossover increases utilization for people with epilepsy: a
      retrospective cohort study.
AB  - OBJECTIVES: "Hospital crossover" occurs when people visit multiple hospitals for
      care, which may cause gaps in electronic health records. Although crossover is
      common among people with epilepsy, the effect on subsequent use of health
      services is unknown. Understanding this effect will help prioritize health care
      delivery innovations targeted for this population. METHODS: We collected de
      identified information from a health information exchange network describing
      7,836 people with epilepsy who visited any of seven hospitals in New York, NY
      from 2009-2012. Data included demographics, comorbidities, and 2 years of visit
      information from ambulatory, inpatient, emergency department (ED), and radiology
      settings. We performed two complementary retrospective cohort analyses, in order
      to (1) illustrate the effect on a carefully selected subgroup, and (2) confirm
      the effect across the study population. First, we performed a matched cohort
      analysis on 410 pairs of individuals with and without hospital crossover in the
      baseline year. Second, we performed a propensity score odds weighted ordinal
      logistic regression analysis to estimate the effect across all 7,836 individuals.
      The outcomes were the use of six health services in the follow-up year. RESULTS:
      In the matched pair analysis, baseline hospital crossover increased the odds of
      more visits in the ED (odds ratio 1.42, 95% confidence interval [CI] 1.05-1.95)
      and radiology settings (1.7, 1.22-2.38). The regression analysis confirmed the ED
      and radiology findings, and also suggested that crossover led to more inpatient
      admissions (1.35, 1.11-1.63), head CTs (1.44, 1.04-2), and brain MRIs (2.32, 1.59
      3.37). SIGNIFICANCE: Baseline hospital crossover is an independent marker for
      subsequent increased health service use in multiple settings among people with
      epilepsy. Health care delivery innovations targeted for people with epilepsy who
      engage in hospital crossover should prioritize (1) sharing radiology images and
      reports (to reduce unnecessary radiology use, particularly head CTs), and (2)
      improving coordination of care (to reduce unnecessary ED and inpatient use).

PMID- 25571987
TI  - Mixed lactate and caffeine compound increases satellite cell activity and
      anabolic signals for muscle hypertrophy.
AB  - We examined whether a mixed lactate and caffeine compound (LC) could effectively
      elicit proliferation and differentiation of satellite cells or activate anabolic
      signals in skeletal muscles. We cultured C2C12 cells with either lactate or LC
      for 6 h. We found that lactate significantly increased myogenin and follistatin
      protein levels and phosphorylation of P70S6K while decreasing the levels of
      myostatin relative to the control. LC significantly increased protein levels of
      Pax7, MyoD, and Ki67 in addition to myogenin, relative to control. LC also
      significantly increased follistatin expression relative to control and stimulated
      phosphorylation of mTOR and P70S6K. In an in vivo study, male F344/DuCrlCrlj rats
      were assigned to control (Sed, n = 10), exercise (Ex, n = 12), and LC
      supplementation (LCEx, n = 13) groups. LC was orally administered daily. The LCEx
      and Ex groups were exercised on a treadmill, running for 30 min at low intensity
      every other day for 4 wk. The LCEx group experienced a significant increase in
      the mass of the gastrocnemius (GA) and tibialis anterior (TA) relative to both
      the Sed and Ex groups. Furthermore, the LCEx group showed a significant increase
      in the total DNA content of TA compared with the Sed group. The LCEx group
      experienced a significant increase in myogenin and follistatin expression of GA
      relative to the Ex group. These results suggest that administration of LC can
      effectively increase muscle mass concomitant with elevated numbers of myonuclei,
      even with low-intensity exercise training, via activated satellite cells and
      anabolic signals. 

PMID- 25571989
TI  - The gain of smooth muscle's contractile capacity induced by tone on in vivo
      airway responsiveness in mice.
AB  - Airway hyperresponsiveness to a spasmogenic challenge such as methacholine, and
      an increased baseline tone measured by the reversibility of airway obstruction
      with a bronchodilator, are two common features of asthma. However, whether the
      increased tone influences the degree of airway responsiveness to a spasmogen is
      unclear. Herein, we hypothesized that increased tone augments airway
      responsiveness in vivo by increasing the contractile capacity of airway smooth
      muscle (ASM). Anesthetized, tracheotomized, paralyzed, and mechanically
      ventilated mice were either exposed (experimental group) or not (control group)
      to tone for 20 min, which was elicited by nebulizing serial small doses of
      methacholine. Respiratory system resistance was monitored during this period and
      the peak response to a large cumulative dose of methacholine was then measured at
      the end of 20 min to assess and compare the level of airway responsiveness
      between groups. To confirm direct ASM involvement, the contractile capacity of
      excised murine tracheas was measured with and without preexposure to tone
      elicited by either methacholine or a thromboxane A2 mimetic (U46619). Distinct
      spasmogens were tested because the spasmogens liable for increased tone in asthma
      are likely to differ. The results indicate that preexposure to tone increases
      airway responsiveness in vivo by 126 +/- 37% and increases the contractile
      capacity of excised tracheas ex vivo by 23 +/- 4% for methacholine and 160 +/-
      63% for U46619. We conclude that an increased tone, regardless of whether it is
      elicited by a muscarinic agonist or a thromboxane A2 mimetic, may contribute to
      airway hyperresponsiveness by increasing the contractile capacity of ASM. 

PMID- 25571988
TI  - No evidence of a role for neuronal nitric oxide synthase in the nucleus tractus
      solitarius in ventilatory responses to acute or chronic hypoxia in awake rats.
AB  - When exposed to a hypoxic environment, the body's first response is a reflex
      increase in ventilation, termed the hypoxic ventilatory response (HVR). With
      chronic sustained hypoxia (CSH), such as during acclimatization to high altitude,
      an additional time-dependent increase in ventilation occurs, which increases the
      HVR and is termed ventilatory acclimatization to hypoxia (VAH). This secondary
      increase persists after exposure to CSH and involves plasticity within the
      circuits in the central nervous system that control breathing. The mechanisms of
      HVR plasticity are currently poorly understood. We hypothesized that changes in
      neuronal nitric oxide synthase (nNOS) activity or expression in the nucleus
      tractus solitarius contribute to this plasticity and underlie VAH in rats. To
      test this, we treated rats held in normoxia or 10% O2 (CSH, PIO2 = 70 Torr) for 7
      9 days and measured ventilation in conscious, unrestrained animals before and
      after microinjecting the general NOS antagonist L-NG-Nitroarginine methyl ester
      into the nucleus tractus solitarius (NTS) or systemically injecting the nNOS
      specific antagonist S-methyl-l-thiocitrulline. Localization of injection sites in
      the NTS was confirmed by histology following the experiment. We found that 1)
      neither NTS-specific nor systemic nNOS antagonism had any effect on hypoxia
      mediated changes in breathing or metabolism (P > 0.05), but 2) nNOS protein
      expression was increased in the middle and caudal NTS by CSH. A persistent HVR
      after nNOS blockade in the NTS contrasts with results in awake mice, and our
      findings do not support the hypotheses that nNOS in the NTS contribute to the HVR
      or VAH in awake rats.

PMID- 25571990
TI  - Extracellular Ca2+-induced force restoration in K+-depressed skeletal muscle of
      the mouse involves an elevation of [K+]i: implications for fatigue.
AB  - We examined whether a Ca(2+)-K(+) interaction was a potential mechanism operating
      during fatigue with repeated tetani in isolated mouse muscles. Raising the
      extracellular Ca(2+) concentration ([Ca(2+)]o) from 1.3 to 10 mM in K(+)
      depressed slow-twitch soleus and/or fast-twitch extensor digitorum longus muscles
      caused the following: 1) increase of intracellular K(+) activity by 20-60 mM
      (raised intracellular K(+) content, unchanged intracellular fluid volume), so
      that the K(+)-equilibrium potential increased by ~10 mV and resting membrane
      potential repolarized by 5-10 mV; 2) large restoration of action potential
      amplitude (16-54 mV); 3) considerable recovery of excitable fibers (~50% total);
      and 4) restoration of peak force with the peak tetanic force-extracellular K(+)
      concentration ([K(+)]o) relationship shifting rightward toward higher [K(+)]o.
      Double-sigmoid curve-fitting to fatigue profiles (125 Hz for 500 ms, every second
      for 100 s) showed that prior exposure to raised [K(+)]o (7 mM) increased, whereas
      lowered [K(+)]o (2 mM) decreased, the rate and extent of force loss during the
      late phase of fatigue (second sigmoid) in soleus, hence implying a K(+)
      dependence for late fatigue. Prior exposure to 10 mM [Ca(2+)]o slowed late
      fatigue in both muscle types, but was without effect on the extent of fatigue.
      These combined findings support our notion that a Ca(2+)-K(+) interaction is
      plausible during severe fatigue in both muscle types. We speculate that a
      diminished transsarcolemmal K(+) gradient and lowered [Ca(2+)]o contribute to
      late fatigue through reduced action potential amplitude and excitability. The
      raised [Ca(2+)]o-induced slowing of fatigue is likely to be mediated by a higher
      intracellular K(+) activity, which prolongs the time before stimulation-induced
      K(+) efflux depolarizes the sarcolemma sufficiently to interfere with action
      potentials. 

PMID- 25571991
TI  - Role of intrinsic aerobic capacity and ventilator-induced diaphragm dysfunction.
AB  - Prolonged mechanical ventilation (MV) leads to rapid diaphragmatic atrophy and
      contractile dysfunction, which is collectively termed "ventilator-induced
      diaphragm dysfunction" (VIDD). Interestingly, endurance exercise training prior
      to MV has been shown to protect against VIDD. Further, recent evidence reveals
      that sedentary animals selectively bred to possess a high aerobic capacity
      possess a similar skeletal muscle phenotype to muscles from endurance trained
      animals. Therefore, we tested the hypothesis that animals with a high intrinsic
      aerobic capacity would naturally be afforded protection against VIDD. To this
      end, animals were selectively bred over 33 generations to create two divergent
      strains, differing in aerobic capacity: high-capacity runners (HCR) and low
      capacity runners (LCR). Both groups of animals were subjected to 12 h of MV and
      compared with nonventilated control animals within the same strains. As expected,
      contrasted to LCR animals, the diaphragm muscle from the HCR animals contained
      higher levels of oxidative enzymes (e.g., citrate synthase) and antioxidant
      enzymes (e.g., superoxide dismutase and catalase). Nonetheless, compared with
      nonventilated controls, prolonged MV resulted in significant diaphragmatic
      atrophy and impaired diaphragm contractile function in both the HCR and LCR
      animals, and the magnitude of VIDD did not differ between strains. In conclusion,
      these data demonstrate that possession of a high intrinsic aerobic capacity alone
      does not afford protection against VIDD. Importantly, these results suggest that
      endurance exercise training differentially alters the diaphragm phenotype to
      resist VIDD. Interestingly, levels of heat shock protein 72 did not differ
      between strains, thus potentially representing an important area of difference
      between animals with intrinsically high aerobic capacity and exercise-trained
      animals. 

PMID- 25571993
TI  - Precedence and autocracy in breathing control.

PMID- 25571992
TI  - Modeling the impairment of airway smooth muscle force by stretch.
AB  - Imposed length changes of only a small percent produce transient reductions in
      active force in strips of airway smooth muscle (ASM) due to the temporary
      detachment of bound cross-bridges caused by the relative motion of the actin and
      myosin fibers. More dramatic and sustained reductions in active force occur
      following large changes in length. The Huxley two-state model of skeletal muscle
      originally proposed in 1957 and later adapted to include a four-state description
      of cross-bridge kinetics has been widely used to model the former phenomenon, but
      is unable to account for the latter unless modified to include mechanisms by
      which the contractile machinery in the ASM cell becomes appropriately rearranged.
      Even so, the Huxley model itself is based on the assumption that the contractile
      proteins are all aligned precisely in the direction of bulk force generation,
      which is not true for ASM. The present study derives a coarse-grained version of
      the Huxley model that is free of inherent assumptions about cross-bridge
      orientation. This simplified model recapitulates the key features observed in the
      force-length behavior of activated strips of ASM and, in addition, provides a
      mechanistically based way of accounting for the sustained force reductions that
      occur following large stretch. 

PMID- 25571994
TI  - Spectral features and perceptual judgment of place of affricate in Putonghua
      speaking pre-adolescents with normal and cleft palate.
AB  - PURPOSE: The aim of the study was to examine the relationship between the
      spectral features and perceptual judgments of places of affricate in Putonghua
      (standard Mandarin Chinese), and to explore the possible contribution of
      different spectral moments on correct perception of place of articulation
      information by typical pre-adolescent speakers and those with cleft palate.
      METHOD: A total of 139 affricates produced by 10 normal pre-adolescent speakers
      and 14 speakers with repaired cleft palate (distorted articulation) were
      presented to 12 listeners tasked with making a judgment of the accuracy of place
      of articulation using a visual analog scale. RESULTS: Statistical analysis showed
      a significant relationship between the third spectral moment (L3) and listeners'
      perceptual judgment of typical alveolar and retroflex affricates. For productions
      by pre-adolescents with cleft palate, the first spectral moment (M1) was
      significantly correlated with listener perceptual scaling of retroflex
      affricates, but not for the alveolar affricates. CONCLUSION: Spectral features
      were associated with the perception of place of affricate in Putonghua. Different
      spectral moment characteristics might be used by listeners when perceiving speech
      from individuals with cleft palate.

PMID- 25571996
TI  - Metabolic pathology of brain inflammation.

PMID- 25571995
TI  - Proceedings of the Thirteenth Annual UT- KBRIN Bioinformatics Summit 2014.

PMID- 25571997
TI  - Changing self-reported physical activity using different types of affectively and
      cognitively framed health messages, in a student population.
AB  - The present research focused upon the power of different messages to increase
      self-reported physical activity (PA). Five hundered and ninety six participants
      were randomised to one of five conditions that varied in the content of message:
      short-term affective, short-term cognitive, long-term affective, long-term
      cognitive and a no message control. PA was measured at baseline and follow-up
      (seven days later) was done using the Godin Leisure Time Exercise Questionnaire
      over the subsequent seven day period. The affective short-term message (ASM) was
      shown to be equally effective at increasing self-reported PA as a cognitive long
      term message. Furthermore, when controlling for baseline activity levels, the ASM
      emerged as being the message that produced the highest levels of self-reported PA
      at follow-up. The findings point to the value of distinguishing between health
      messages in terms of the focus on affective and cognitive outcomes and the
      temporal nature of the outcomes (short-term or long-term).

PMID- 25571998
TI  - Cerebellar injury in preterm children with cerebral palsy after intraventricular
      hemorrhage: Prevalence and relationship to functional outcomes.
AB  - OBJECTIVES: To elucidate the prevalence of cerebellar injury and its relationship
      to functional outcomes in preterm children with cerebral palsy (CP) after
      intraventricular hemorrhage (IVH). PARTICIPANTS: We selected 69 children (40
      males and 29 females, aged between 6 and 13 years) out of 2049 with cerebral
      palsy who visited Morinomiya Hospital, the regional center hospital for CP in
      West Japan. The inclusion criteria were (1) gestational age under 36 weeks at
      birth, (2) clear history of postnatal intraventricular hemorrhage, and (3) age at
      investigation over 6 years old. Those without sufficient imaging study or
      functional evaluation were excluded. METHODS: The participants were divided into
      four groups according to the presence of post-hemorrhagic hydrocephalus (PH) and
      cerebellar injury (CI): PH+/CI+, PH+/CI-, PH-/CI+, and PH-/CI-. Type of CP,
      ability to walk, verbal function, the incidence of severe visual impairment, and
      the complication of epilepsy were investigated and compared among the groups.
      RESULTS: The gestational ages of the participants were between 22 and 34 weeks,
      and their birth weight was between 412 and 1788 g. PH and CI were found in 39
      (57%) and 40 (58%) children, respectively. Both the PH+/CI+ group (n=31) and the
      PH-/CI+ group (n=9) showed significantly lower walking and verbal abilities and a
      higher incidence of epilepsy than the PH-/CI- group (n=21), while the PH+/CI-
      group showed no significant difference from the PH-/CI- group. Severe visual
      impairment was found only in the PH+/CI+ group and the PH-/CI+ group.
      CONCLUSIONS: The prevalence of CI in preterm children with CP after IVH (58%) was
      almost the same as that of PH. CI is one of the most significant complications in
      preterm infants, affecting motor and verbal functions and being associated with
      epilepsy more than PH.

PMID- 25571999
TI  - Upregulation of RBFOX1 in the malformed cortex of patients with intractable
      epilepsy and in cultured rat neurons.
AB  - Mutations in RNA-binding Fox 1 (RBFOX1) are known to be associated with
      neurodevelopmental disorders including epilepsy, mental retardation and autism
      spectrum disorder. The deletion of the Rbfox1 gene in mice has been shown to
      result in heightened susceptibility to seizures. However, other studies have
      revealed mutations or the downregulation of RBFOX1 in specimens obtained from
      patients with epilepsy or malformations of cortical development (MCD). Generally,
      the expression of RBFOX1 varies according to tissue type. In this study, we
      demonstrated the upregulation of RBFOX1 protein in the cortex of patients with
      MCD and intractable epilepsy. Electrophysiological recordings of cultured rat
      cortical neurons with increased Rbfox1 expression also revealed a significantly
      increased amplitude of action potential (AP) and Na+ current density. Some of
      these neurons (26.32%) even displayed spontaneous, recurrent, epileptiform
      discharges (SREDs). Additionally, certain Rbfox1 target transcripts associated
      with epilepsy, including glutamate receptor, ionotropic, N-methyl D-aspartate 1
      [Grin1, also known as N-methyl-D-aspartate receptor subunit NR1 (NMDAR1)],
      synaptosomal-associated protein, 25 kDa (SNAP-25 or Snap25) and sodium channel,
      voltage gated, type VIII, alpha subunit (Scn8a, also known as Nav1.6) were
      identified to be upregulated in these cultured cortical neurons with an
      upregulated Rbfox1 expression. These data suggest that the upregulation of RBFOX1
      contributes to neuronal hyperexcitation and seizures. The upregulation of NMDAR1
      (Grin1), SNAP-25 (Snap25) and Scn8a may thus be involved in Rbfox1-related
      neuronal hyperexcitation.

PMID- 25572000
TI  - Angiotensin II promotes differentiation of mouse c-kit-positive cardiac stem
      cells into pacemaker-like cells.
AB  - Cardiac stem cells (CSCs) can differentiate into cardiac muscle-like cells;
      however, it remains unknown whether CSCs may possess the ability to differentiate
      into pacemaker cells. The aim of the present study was to determine whether
      angiotensin II (Ang II) could promote the specialization of CSCs into pacemaker
      like cells. Mouse CSCs were treated with Ang II from day 3-5, after cell sorting.
      The differentiation potential of the cells was then analyzed by morphological
      analysis, flow cytometry, reverse transcription-polymerase chain reaction,
      immunohistochemistry and patch clamp analysis. Treatment with Ang II resulted in
      an increased number of cardiac muscle-like cells (32.7 +/- 4.8% vs. 21.5 +/-
      4.8%; P<0.05), and inhibition of smooth muscle-like cells (6.2 +/- 7.3% vs. 20.5
      +/- 5.1%; P<0.05). Following treatment with Ang II, increased levels of the
      cardiac progenitor-specific markers GATA4 and Nkx2.5 were observed in the cells.
      Furthermore, the transcript levels of pacemaker function-related genes, including
      hyperpolarization-activated cyclic nucleotide-gated (HCN)2, HCN4, T-box (Tbx)2
      and Tbx3, were significantly upregulated. Immunofluorescence analysis confirmed
      the increased number of pacemaker-like cells. The pacemaker current (If) was
      recorded in the cells derived from CSCs, treated with Ang II. In conclusion,
      treatment of CSCs with Ang II during the differentiation process modified cardiac
      specific gene expression and resulted in the enhanced formation of pacemaker-like
      cells.

PMID- 25572001
TI  - Ubiquitin ligase Siah1 promotes the migration and invasion of human glioma cells
      by regulating HIF-1alpha signaling under hypoxia.
AB  - It has been reported that by regulating PHD3 stability, Siah1 contributes to the
      abundance of hypoxia-inducible factor (HIF)-1alpha, thereby playing an important
      role in the cellular response to hypoxia. However, the expression level and
      functional significance of Siah1 in human malignant glioma, which is
      characterized by high migration and invasion potential, have never been
      investigated. We report here, that Siah1 was expressed highly in human glioma
      tissues compared with its expression in normal brain tissues and was correlated
      with advanced tumor status and stage. The knockdown of Siah1 by short-hairpin RNA
      severely suppressed the migration and invasion of human glioma U251 cells under
      hypoxia, while overexpression of Siah1 promoted it. Furthermore, we demonstrated
      that the glioma cell migration and invasion under hypoxia mediated by Siah1 was
      achieved by reducing the stability of PHD3, which protected the HIF-1alpha from
      degradation. These findings suggest that Siah1 plays important roles in the
      migration and invasion of human glioma cells under hypoxia, which may provide
      some guidance for the targeted therapy of human glioma based on the interference
      of the Siah1-PHD3-HIF-1alpha signaling pathway.

PMID- 25572003
TI  - Experimental models of bone metastasis: Opportunities for the study of cancer
      dormancy.
AB  - Skeletal metastasis is prevalent in many cancers, and has been the subject of
      intense research, yielding innovative models to study the multiple stages of
      metastasis. It is now evident that, in the early stages of metastatic spread,
      disseminated tumour cells in the bone undergo an extended period of growth arrest
      in response to the microenvironment, a phenomenon known as "dormancy". Dormancy
      has been implicated with drug resistance, while enforced dormancy has also been
      seen as a radical method to control cancer, and engineering of dormant states has
      emerged as a novel clinical strategy. Understanding of the subject, however, is
      limited by the availability of models to describe early stages of metastatic
      spread. This mini-review provides a summary of experimental models currently
      being used in the study of bone metastasis and the applications of these models
      in the study of dormancy. Current research in developing improved models is
      described, leading to a discussion of challenges involved in future developments.

PMID- 25572002
TI  - Glutamatergic and dopaminergic neurons in the mouse ventral tegmental area.
AB  - The ventral tegmental area (VTA) comprises dopamine (DA), gamma-aminobutyric acid
      (GABA) and glutamate (Glu) neurons. Some rat VTA Glu neurons, expressing
      vesicular glutamate transporter 2 (VGluT2), co-express tyrosine hydroxylase (TH).
      While transgenic mice are now being used in attempts to determine the role of
      VGluT2/TH neurons in reward and neuronal signaling, such neurons have not been
      characterized in mouse tissue. By cellular detection of VGluT2 mRNA and TH
      immunoreactivity (TH-IR), we determined the cellular expression of VGluT2 mRNA
      within VTA TH-IR neurons in the mouse. We found that some mouse VGluT2 neurons
      coexpressed TH-IR, but their frequency was lower than in the rat. To determine
      whether low expression of TH mRNA or TH-IR accounts for this low frequency, we
      evaluated VTA cellular coexpression of TH transcripts and TH protein. Within the
      medial aspects of the VTA, some neurons expressed TH mRNA but lacked TH-IR; among
      them a subset coexpressed VGluT2 mRNA. To determine if lack of VTA TH-IR was due
      to TH trafficking, we tagged VTA TH neurons by Cre-inducible expression of
      mCherry in TH::Cre mice. By dual immunofluorescence, we detected axons containing
      mCherry, but lacking TH-IR, in the lateral habenula, indicating that low
      frequency of VGluT2 mRNA (+)/TH-IR (+) neurons in the mouse is due to lack of
      synthesis of TH protein, rather than TH protein trafficking. In conclusion,
      VGluT2 neurons are present in the rat and mouse VTA, but they differ in the
      populations of VGluT2/TH and TH neurons. Under normal conditions, the translation
      of TH protein is suppressed in the mouse mesohabenular TH neurons. 

PMID- 25572004
TI  - Puts the magic back into life: Fathers' experience of planned home birth.
AB  - BACKGROUND: In Ireland, planned home birth is seen as an alternative but safe
      choice of maternity care. Women's experience of home birth is reported as
      positive but little is known about fathers' thoughts and feelings about planned
      home birth. AIM: The aim of the study was to explore fathers' experience of
      planned home birth. METHOD: Hermeneutic phenomenology was selected to explore the
      experiences of eight fathers whose partners had a recent planned home birth. Data
      were analysed using Interpretative Phenomenological Analysis (IPA). RESULTS:
      Themes identified were 'negotiating the decision', 'ownership of the birth' and
      'changed way of being'. Fathers overcame their initial reservations about home
      birth before the decision to plan a home birth was agreed. They were actively
      involved with their partner in labour which gave themselves a sense of ownership
      of the experience and a valued post-birth intimacy. Their belief in natural birth
      was reaffirmed and the experience gave them a new perspective on life.
      CONCLUSION: When men have a positive experience of childbirth they benefit
      personally and emotionally. This experience can strengthen their relationship
      with their partner and the family. Midwives are ideally placed to involve fathers
      actively in birth either in a home or hospital setting.

PMID- 25572006
TI  - Placement of an RV Lead Through the Lung Parenchyma.

PMID- 25572007
TI  - Comorbidity in Patients With Small-Cell Lung Cancer: Trends and Prognostic
      Impact.
AB  - INTRODUCTION: We evaluated the trends in the prevalence of comorbidity and its
      prognostic impact in a cohort of unselected patients with small-cell lung cancer
      (SCLC). PATIENTS AND METHODS: All patients (n = 4142) diagnosed with SCLC from
      1995 to 2012 were identified from the population-based Netherlands Cancer
      Registry in the Eindhoven region. RESULTS: The prevalence of comorbidity
      increased from 55% in 1995 to 1998 to 76% in 2011 to 2012 and multimorbidity (ie,
      >= 2 concomitant diseases) from 23% to 51%. The prevalence of a comorbidity
      increased with age. Among the men, hypertension, cardiac disease, and diabetes,
      in particular, became more common (increased from 11% to 35%, from 19% to 36%,
      and from 7% to 18%, respectively). In the women, the rate of pulmonary disease,
      hypertension, and cardiac disease increased the most (increased from 18% to 30%,
      from 12% to 28%, and from 11% to 24%, respectively). Multimorbidity was
      associated with a slightly increased hazard of death, independent of treatment in
      those with limited-stage SCLC (hazard ratio [HR] for >= 2 comorbidities vs. no
      comorbidities, 1.2; 95% confidence interval [CI], 1.0-1.4). The prognostic
      effects of multimorbidity resulted from treatment in those with extensive-stage
      SCLC (HR for >= 2 comorbidities vs. no comorbidities, final model, 1.2; 95% CI,
      1.0-1.2). The prognostic impact of the specific comorbidities varied, with
      digestive disease reducing the hazard and cardiac disease increasing the hazard
      in those with limited-stage SCLC (HR for digestive disease vs. no digestive
      disease, 0.7 [95% CI, 0.5-0.9], and HR for cardiac vs. no cardiac disease, 1.2
      [95% CI, 1.0-1.3]). Also, cardiac and cerebrovascular disease increased the
      hazard in those with extensive-stage SCLC (HR 1.2 [95% CI, 1.0-1.3] and HR 1.3
      [95% CI, 1.1-1.6], respectively). CONCLUSION: Comorbidity among patients with
      SCLC is very common and has been increasing. Multimorbidity was associated with a
      slightly increased hazard of death in those with limited-stage SCLC, independent
      of treatment. However, the prognostic effects in those with advanced-stage SCLC
      resulted from treatment. Digestive disease favorably affected survival and
      cardiac disease negatively affected the prognosis for those with limited-stage
      SCLC, and cardiac and cerebrovascular diseases had a negative prognostic effect
      for those with extensive-stage SCLC. With the burden of comorbidities in patients
      with SCLC increasing, more attention to individualized treatment approaches is
      needed.

PMID- 25572005
TI  - Beyond traditional pharmacology: new tools and approaches.
AB  - Traditional pharmacology is defined as the science that deals with drugs and
      their actions. While small molecule drugs have clear advantages, there are many
      cases where they have proved to be ineffective, prone to unacceptable side
      effects, or where due to a particular disease aetiology they cannot possibly be
      effective. A dominant feature of the small molecule drugs is their single
      mindedness: they provide either continuous inhibition or continuous activation of
      the target. Because of that, these drugs tend to engage compensatory mechanisms
      leading to drug tolerance, drug resistance or, in some cases, sensitization and
      consequent loss of therapeutic efficacy over time and/or unwanted side effects.
      Here we discuss new and emerging therapeutic tools and approaches that have
      potential for treating the majority of disorders for which small molecules are
      either failing or cannot be developed. These new tools include biologics, such as
      recombinant hormones and antibodies, as well as approaches involving gene
      transfer (gene therapy and genome editing) and the introduction of specially
      designed self-replicating cells. It is clear that no single method is going to be
      a 'silver bullet', but collectively, these novel approaches hold promise for
      curing practically every disorder.

PMID- 25572008
TI  - Weekly nab-paclitaxel in combination with carboplatin as first-line therapy in
      patients with advanced non-small-cell lung cancer: analysis of safety and
      efficacy in patients with renal impairment.
AB  - INTRODUCTION: Renal impairment in cancer patients can affect treatment
      tolerability and outcomes. This analysis evaluated the safety and efficacy of nab
      paclitaxel (nab-P) versus solvent-based paclitaxel (sb-P), both in combination
      with carboplatin (C), in patients with advanced non-small-cell lung cancer
      (NSCLC) and renal impairment. METHODS: Untreated patients with stage IIIB/IV
      disease with NSCLC and a performance status of 0/1 were randomly assigned (1:1)
      to receive 100 mg/m(2)nab-P weekly plus C (under the curve = 6, every 3 weeks) or
      200 mg/m(2) sb-P plus C (under the curve = 6) every 3 weeks. The primary end
      point was overall response rate. RESULTS: Of 1038 treated patients in the phase
      III trial, 38% had mild renal impairment (creatinine clearance > 50 to <= 80
      mL/min; n = 198 for nab-P/C and n = 206 for sb-P/C) and 5% had moderate renal
      impairment (creatinine clearance <= 50 mL/min: n = 26 for nab-P/C and n = 27 for
      sb-P/C). For nab-P/C versus sb-P/C, the treatment difference in efficacy in
      patients with either level of renal impairment was comparable to the overall
      population but did not reach statistical significance, with an overall response
      rate of 35% versus 27% (response rate ratio, 1.324; P = .060) in patients with
      mild renal impairment, and 31% versus 19% (response rate ratio, 1.662; P = .300)
      in patients with moderate renal impairment. Overall survival and progression-free
      survival were nonsignificantly longer for nab-P/C versus sb-P/C in these subsets.
      Patients with renal impairment experienced less grade 3 or higher neutropenia and
      sensory neuropathy, but more thrombocytopenia and anemia with nab-P/C versus sb
      P/C. CONCLUSION: nab-P/C proved beneficial and tolerable in patients with
      advanced NSCLC and mild and moderate renal impairment.

PMID- 25572009
TI  - Relationship between in vitro drug sensitivity and clinical response of patients
      to treatment in chronic lymphocytic leukemia.
AB  - To improve the efficacy of therapeutic options in chronic lymphocytic leukemia
      (CLL) an in vitro system to determine the response of mononuclear blood cells
      from blood of patients was elaborated. The study combines four approaches, i.e.,
      cell viability, apoptosis rate, differential scanning calorimetry (DSC), and
      immunoblotting to develop personalized therapy protocols based on the cell
      sensitivity to drug exposure of individual CLL patients. The complementary
      analyses were performed on 28 peripheral blood samples from previously untreated
      CLL patients before therapy. The induction and progress of apoptosis in CLL cells
      exposed in vitro to purine analogs combined with mafosfamide, i.e., cladribine +
      mafosfamide (CM) and fludarabine + mafosfamide (FM) were assessed using the above
      approaches. The changes in thermal profiles (decrease/loss of transition at 95+/
      5C) coincided with an accumulation of apoptotic cells, a decrease in the number
      of viable cells, and differences in the expression of the apoptosis-related
      protein PARP-1. No significant changes were observed in the thermal profiles of
      nuclei isolated from CLL cells resistant to the treatment. The complementary
      assays revealed a strong relationship between both the in vitro sensitivity of
      leukemia cells to drugs and the clinical response of the patients, determined
      usually after the sixth course of treatment (after ~6 months of therapy). As a
      summary of studies followed by complementary tests, our findings demonstrate the
      value of in vitro exposure of CLL cell samples to drugs intended to treat CLL
      patients, before their administration in order to recommend the most suitable and
      effective therapy for individual patients.

PMID- 25572011
TI  - Genetics of congenital heart disease: Beyond half-measures.

PMID- 25572010
TI  - Ablation of atrial fibrillation.
AB  - Ablation is increasingly used to treat AF, since recent trials of pharmacological
      therapy for AF have been disappointing. Ablation has been shown to improve
      maintenance of sinus rhythm compared to pharmacological therapy in many
      multicenter trials, although success rates remain suboptimal. This review will
      discuss several trends in the field of catheter ablation, including studies to
      advance our understanding of AF mechanisms in different patient populations,
      innovations in detecting and classifying AF, use of this information to improve
      strategies for ablation, technical innovations that have improved the ease and
      safety of ablation, and novel approaches to surgical therapy and imaging. These
      trends are likely to further improve results from AF ablation in coming years as
      it becomes an increasingly important therapeutic option for many patients. 

PMID- 25572012
TI  - The leading edge of vascular calcification.

PMID- 25572014
TI  - Hypolipidemic and anti-atherogenic effect of aqueous extract leaves of Ficus
      glumosa (Moraceae) in rats.
AB  - Leaves of Ficus glumosa are used in northern Cameroon and southern Chad for the
      treatment of cardiovascular diseases, as food and as a stimulant for milk
      production in both women and animals. Atherosclerosis is a disease in which
      frequency increases with age. The first lesions appear at the young subject
      during adolescence. Atherosclerosis lesions appear very precociously and worsen
      with age. They interest the levels chronologically aortic, coronary then carotid.
      Age is a risk factor in that it reflects the exposure time of individual to the
      other risk factors. The frequency of the atherosclerosis increases with age
      because of the aging of the cells. This study was undertaken to evaluate the
      hypolipidemic and anti-atherosclerotic properties of aqueous extract of the
      leaves of F. glumosa in rats with hypercholesterolemia (HC). 60 male rats were
      fed for 4 weeks with a high-cholesterol diet (1%) and 3 doses (225, 300 and 375
      mg/kg) of extract of F. glumosa were used in these experiments. The experiments
      were conducted under the same conditions with atorvastatin (1 mg/kg), as
      pharmacological reference substance. The effects of F. glumosa on weight gain,
      water and food consumption, levels of serum lipids and lipoprotein lipid
      oxidation and stress markers in the blood and liver were examined. The
      administration of F. glumosa extract prevented significant (P<0.05) elevation in
      TC, LDL-c, VLDL-c, hepatic and aortic TG and TC. The atherogenic, triglyceride,
      and lipid peroxidation (TBARS) indexes were also decreased in the rats treated
      with the extract. F. glumosa favored the performance of fecal cholesterol. It
      also significantly inhibited the changes and the formation of aortic
      atherosclerotic plaques. These results revealed the hypolipidemic and
      antiatherosclerotic effects of F. glumosa extract and support the traditional use
      of the extract of this plant in the treatment of hypertension and diabetes.

PMID- 25572013
TI  - Higher levels of adiponectin in vascular endothelial cells are associated with
      greater brachial artery flow-mediated dilation in older adults.
AB  - Adiponectin, an adipocyte-derived protein, exerts anti-atherosclerotic effects on
      the vascular endothelium. Recently adiponectin protein has been reported in
      murine vascular endothelial cells, however, whether adiponectin is present in
      human vascular endothelial cells remains unexplored. We sought to examine 1)
      adiponectin protein in vascular endothelial cells collected from older adults
      free of overt cardiovascular disease; 2) the relation between endothelial cell
      adiponectin and in vivo vascular endothelial function; and 3) the relation
      between endothelial cell adiponectin, circulating (plasma) adiponectin and
      related factors. We measured vascular endothelial function (brachial artery flow
      mediated dilation using ultrasonography), vascular endothelial cell adiponectin
      (biopsy coupled with quantitative immunofluorescence) and circulating adiponectin
      (Mercodia, ELISA) in older, sedentary, non-smoking, men and women (55-79 years).
      We found that higher endothelial cell adiponectin was related with greater flow
      mediated dilation (r = 0.43, P < 0.05) and greater flow-mediated dilation
      normalized for shear stress (r = 0.56, P < 0.01), but was not related with
      vascular smooth muscle responsiveness to nitric oxide (r = 0.04, P = 0.9).
      Vascular endothelial cell adiponectin was not related with circulating
      adiponectin (r = -0.14, P = 0.6). Endothelial cell and circulating adiponectin
      were differentially associated with adiposity, metabolic and other factors, but
      both were inversely associated with renal function (r = 0.44 to 0.62, P <= 0.04).
      In conclusion, higher endothelial cell adiponectin levels are associated with
      higher vascular endothelial function, independent of circulating adiponectin
      levels in older adults.

PMID- 25572015
TI  - Spondyloarthritis and the gut: a new look.

PMID- 25572016
TI  - 205th ENMC International Workshop: Pathology diagnosis of idiopathic inflammatory
      myopathies part II 28-30 March 2014, Naarden, The Netherlands.

PMID- 25572017
TI  - Investigation of vacuum forming techniques for reduction of loss in mouthguard
      thickness: part 2-effects of sheet grooving and thermal shrinkage.
AB  - The aim of this study was to investigate vacuum forming techniques for reduction
      of loss in mouthguard thickness effects of sheet grooving and thermal shrinkage
      of extruded sheets on molded mouthguard thickness. Mouthguards were fabricated
      with ethylene vinyl acetate (EVA) sheets (4.0 mm thick) using a vacuum forming
      machine. Sheet form was a convexing v-shaped groove toward the back, 10-40 mm
      from the anterior end. The sheets were placed in the forming machine with the
      sheet extrusion direction either vertical or parallel to the model's centerline
      of right and left. Molding was performed by crimping the sheet using suction when
      the most descending portion of the sheet sagged downwards from the clamp, 15 mm
      below the basal surface. Postmolding thickness was determined using a measuring
      device. Measurement points were the incisal portion (incisal edge and labial
      surface) and molar portion (cusp and buccal surface). Differences in molded
      mouthguard thickness with the sheet orientation of extruded EVA sheets were
      analyzed by student's t-test. The sheet in parallel axis orientation with the
      model's centerline yielded higher thickness than vertical orientation at the
      labial surface and the buccal surface. The present results suggested that
      addition of a groove to the sheet in conjunction with placement of the sheet with
      its axis of orientation parallel the centerline of the working model can
      effectively reduce thickness loss in the molded mouthguard with the equipment and
      materials used in this study.

PMID- 25572018
TI  - Metagenome assembly through clustering of next-generation sequencing data using
      protein sequences.
AB  - The study of environmental microbial communities, called metagenomics, has gained
      a lot of attention because of the recent advances in next-generation sequencing
      (NGS) technologies. Microbes play a critical role in changing their environments,
      and the mode of their effect can be solved by investigating metagenomes. However,
      the difficulty of metagenomes, such as the combination of multiple microbes and
      different species abundance, makes metagenome assembly tasks more challenging. In
      this paper, we developed a new metagenome assembly method by utilizing protein
      sequences, in addition to the NGS read sequences. Our method (i) builds read
      clusters by using mapping information against available protein sequences, and
      (ii) creates contig sequences by finding consensus sequences through
      probabilistic choices from the read clusters. By using simulated NGS read
      sequences from real microbial genome sequences, we evaluated our method in
      comparison with four existing assembly programs. We found that our method could
      generate relatively long and accurate metagenome assemblies, indicating that the
      idea of using protein sequences, as a guide for the assembly, is promising. 

PMID- 25572019
TI  - Factor Xa dimerization competes with prothrombinase complex formation on platelet
      like membrane surfaces.
AB  - Exposure of phosphatidylserine (PS) molecules on activated platelet membrane
      surface is a crucial event in blood coagulation. Binding of PS to specific sites
      on factor Xa (fXa) and factor Va (fVa) promotes their assembly into a complex
      that enhances proteolysis of prothrombin by approximately 105. Recent studies
      demonstrate that both soluble PS and PS-containing model membranes promote
      formation of inactive fXa dimers at 5 mM Ca2+. In the present study, we show how
      competition between fXa dimerization and prothrombinase formation depends on Ca2+
      and lipid membrane concentrations. We used homo-FRET measurements between
      fluorescein-E-G-R-chloromethylketone (CK)-Xa [fXa irreversibly inactivated by
      alkylation of the active site histidine residue with FEGR (FEGR-fXa)] and
      prothrombinase activity measurements to reveal the balance between fXa dimer
      formation and fXa-fVa complex formation. Changes in FEGR-fXa dimer homo-FRET with
      addition of fVa to model-membrane-bound FEGR-fXa unambiguously demonstrated that
      formation of the FEGR-fXa-fVa complex dissociated the dimer. Quantitative global
      analysis according to a model for protein interaction equilibria on a surface
      provided an estimate of a surface constant for fXa dimer dissociation
      (K(fXa*fXa)(d, sigma)) approximately 10-fold lower than K(fXa*fVa)(d,sigma) for
      fXa-fVa complex. Experiments performed using activated platelet-derived
      microparticles (MPs) showed that competition between fXa dimerization and fXa-fVa
      complex formation was even more prominent on MPs. In summary, at Ca2+
      concentrations found in the maturing platelet plug (2-5 mM), fVa can compete fXa
      off of inactive fXa dimers to significantly amplify thrombin production, both
      because it releases dimer inhibition and because of its well-known cofactor
      activity. This suggests a hitherto unanticipated mechanism by which PS-exposing
      platelet membranes can regulate amplification and propagation of blood
      coagulation.

PMID- 25572020
TI  - Impact of preprocedural high-sensitive C-reactive protein levels on long-term
      clinical outcomes of patients with stable coronary artery disease and chronic
      kidney disease who were treated with drug-eluting stents.
AB  - BACKGROUND: To evaluate the prognostic impact of preprocedural high-sensitivity C
      reactive protein (hsCRP) levels on the long-term clinical outcomes after first
      generation drug-eluting stent (DES) implantation in chronic kidney disease (CKD)
      patients with stable coronary artery disease (CAD). METHODS AND RESULTS: We found
      significant interaction between CKD and hsCRP levels (p=0.0138) in 1176
      consecutive patients with stable CAD who were treated with first-generation DES
      implantation between 2004 and 2009 at our institution. Therefore, we separately
      analyzed data from patients with and without CKD who were assigned to tertiles
      based on preprocedural hsCRP levels. We evaluated the incidence of major adverse
      cardiovascular events (MACE) comprising all-cause death, nonfatal myocardial
      infarction, and target vessel revascularization after percutaneous coronary
      intervention during a median follow-up period of 1266 days. The rate of MACE
      significantly differed among the tertiles (log-rank p=0.0074) in the group with
      CKD. Multivariate Cox regression analysis significantly associated a higher hsCRP
      tertile with MACE in the CKD group (hazard ratio 2.39, 95% confidence interval
      1.27-4.75, p=0.0062). CONCLUSION: Elevated preprocedural serum hsCRP levels might
      be associated with the long-term clinical outcomes of patients with stable CAD
      and CKD who were implanted with first-generation DES.

PMID- 25572021
TI  - Echocardiographic screening for congenital heart disease in 8819 children: A
      report from local community events for children's healthcare.
AB  - BACKGROUND: We had the opportunity to perform echocardiographic screening of
      children at local community events for children's healthcare sponsored by the
      prefectural government. The aim of this study was to assess the utility of
      echocardiographic screening by measuring the prevalence of congenital heart
      disease (CHD) and abnormal findings in children without history of diagnosed CHD.
      METHODS: Subjects consisted of 8819 infants and preschool children (1 month to 6
      years) who underwent echocardiographic examination at public events from 2001 to
      2013. Children with known CHD were excluded. RESULTS: We performed
      echocardiographic screening on 752 (range: 464-993) children at each event. At a
      total of 12 events, subjects consisted of 3175 infants less than one year (36%),
      2292 one-year-olds (26%), 1058 two-year-olds (12%), 794 three-year-olds (9%), and
      other children up to age six years. We identified echocardiographic abnormalities
      in 137 children (15.5/1000 subjects), and 89 children (10.1/1000 subjects) were
      diagnosed with CHD. The prevalence of an echocardiographic abnormality did not
      change over the 12-year period (Kendall's tau=-0.272, p=0.19). CONCLUSIONS: CHD
      which could not be identified by prenatal echocardiography and neonatal
      auscultation could be detected in a substantial number of young children by
      echocardiographic screening. Echocardiographic screening may be useful for early
      diagnosis of CHD. However, our study is based on cross-sectional data without
      follow-up. Larger prospective studies are needed to verify the utility of
      echocardiographic screening with follow-up data in this cohort.

PMID- 25572022
TI  - Relation between stent thrombosis and calcium channel blocker after drug-eluting
      stent implantation: Kumamoto Intervention Conference Study (KICS) registry.
AB  - BACKGROUND: Stent thrombosis (ST) has emerged as a severe complication of
      percutaneous coronary intervention (PCI). Since the occurrence of ST is lower in
      Japan than Western countries, there are few data to predict ST after drug-eluting
      stent (DES) implantation in Japan. We examined the independent predictors of ST
      incidence after DES implantation in Japanese patients, including the use of
      calcium channel blockers (CCBs). METHODS AND RESULTS: We used data from the
      Kumamoto Intervention Conference Study registry. There were 6286 consecutive
      patients enrolled from June 2008 to March 2011. Among them, we analyzed 3493
      patients who underwent DES implantation. The incidence of definite/probable ST
      throughout a median follow-up period of 364 days was 0.57% (20 patients). There
      were 8 patients with early ST (within 30 days), 8 patients with late ST (between
      31 and 365 days), and 4 patients with very late ST (after 1 year). The frequency
      of CCB use was significantly lower in ST than non-ST patients (25.0% versus
      51.4%, respectively, p=0.016). Multiple regression analysis showed that longer
      stent length (p=0.034), acute coronary syndrome (p=0.039), and the absence of CCB
      use (p=0.046) were significant and independent predictors of ST within 1 year.
      CONCLUSIONS: These results suggest that CCB use may be associated with a
      decreased risk of ST after DES implantation within 1 year in Japanese patients.

PMID- 25572023
TI  - One-year outcomes in unselected patients treated with a thin-strut, platinum
      chromium, paclitaxel-eluting stent: primary endpoint results from the TAXUS
      Element European post-approval surveillance study (TE-PROVE).
AB  - AIMS: To evaluate clinical outcomes in patients receiving the next-generation,
      paclitaxel-eluting, platinum-chromium TAXUS Element stent in a real-world
      setting. The PERSEUS Workhorse and Small Vessel studies showed positive results
      with the TAXUS Element stent in a clinical trial setting. METHODS AND RESULTS: TE
      PROVE was a prospective, open-label, multicentre, "all-comers" study which
      enrolled 1,014 patients at 37 European sites. Follow-up was at 30 days, six
      months and one year, and will continue annually up to five years. The primary
      endpoint was overall and stent-related target vessel failure (TVF), defined as
      cardiac death, target vessel-related myocardial infarction (MI) and target vessel
      revascularisation (TVR) at one year post implantation. Secondary endpoints
      included the components of TVF, all-cause mortality, and ARC definite/probable
      stent thrombosis. Follow-up was available in 97.3% (987/1,014) of patients.
      Patients were 75.0% male (760/1,014), mean age was 65.1+/-10.8 years, 25.5% had
      medically treated diabetes (259/1,014), and 10.7% (109/1,014) were treated for
      STEMI. At baseline, mean lesion length among 1,299 treated lesions was 19.8+/
      12.0 mm and mean reference vessel diameter was 3.1+/-0.5 mm. At one year, the
      rate of TVF (primary endpoint) was 6.0% (59/987) overall; 3.7% (37/987) of TVF
      events were stent-related. Cardiac death was 0.7% (7/987), target vessel-related
      MI was 1.1% (11/987), and TVR was 4.7% (46/987). All-cause death occurred in 1.2%
      (12/987) of patients and ARC definite/probable ST was 0.5% (5/987). CONCLUSIONS:
      The primary endpoint results from the TE-PROVE registry demonstrate good
      performance and safety for the TAXUS Element paclitaxel-eluting stent at one year
      in everyday clinical practice. CLINICAL TRIAL REGISTRATION INFORMATION:
      NCT01242696.

PMID- 25572024
TI  - Efficacy of different devices for transcatheter closure of patent foramen ovale
      assessed by serial transoesophageal echocardiography and rates of recurrent
      cerebrovascular events in a long-term follow-up.
AB  - AIMS: Closure of patent foramen ovale (PFO) is non-inferior to medical treatment
      for patients with cryptogenic stroke. Results in randomised trials might be based
      on the different types of used occluders. We determined residual shunting with
      serial contrast transoesophageal echocardiography (cTEE) and evaluated rates of
      recurrent cerebrovascular events in a long-term follow-up. METHODS AND RESULTS:
      cTEE was repeated three and 12 months after PFO closure using AMPLATZER (n=109),
      BioSTAR (n=68), Cardia (n=104) or Premere (n=54) occluders. Closure was
      demonstrated in 91.6% and 95.9% of patients after three and 12 months. Closure
      rates were not different among groups (p=0.58; p=0.94). The PFO diameter was a
      risk factor for residual shunting (p=0.02), but not the prevalence of an atrial
      septal aneurysm (ASA). During follow-up, including 1,815 patient-years (PY),
      eight patients suffered a stroke (0.44/100 PY) and seven patients a transient
      ischaemic attack (0.39/100 PY). Rates of recurrent cerebrovascular events were
      similar among the four groups. CONCLUSIONS: Closure at three or 12 months (as
      measured by cTEE) and rates of recurrent cerebrovascular events were similar
      among occluder groups. PFO diameter was a risk factor for residual shunting, but
      not the presence of ASA. The rate of recurrent cerebral ischaemic events was low.

PMID- 25572025
TI  - Long-term follow-up of second-generation everolimus-eluting stents versus first
      generation sirolimus-eluting stents in acute myocardial infarction: three-year
      results of the XAMI trial.
AB  - AIMS: Evaluation of the long-term safety and efficacy of second-generation
      everolimus-eluting stents (EES) versus first-generation sirolimus-eluting stents
      (SES) in acute myocardial infarction (AMI) patients. METHODS AND RESULTS: Six
      hundred and twenty-five patients were randomised (2:1) to EES or SES in the
      multicentre XAMI (XienceV stent vs. Cypher stent in Primary PCI for Acute
      Myocardial Infarction) trial. The primary endpoint was cardiac death, non-fatal
      AMI or any target vessel revascularisation (TVR) at one year, with a planned
      follow-up of three years. At three-year follow-up, the primary endpoint was 8.0%
      for EES and 10.5% for SES (p=0.30). Cardiac death was low and comparable in both
      groups (EES: 2.5% versus SES: 2.7%; p=0.86), as was definite/probable stent
      thrombosis (EES: 2.3% versus SES 3.2%; p=0.60). CONCLUSIONS: The event rate at
      three years in this all-comer, randomised, multicentre AMI trial was low,
      including stent thrombosis, with no significant difference between first- and
      second-generation DES. Registration of
      trial:http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1123 Candidate
      number: 2869; NTR number: NTR1123.

PMID- 25572026
TI  - Five-year results of a randomised comparison of titanium-nitride-oxide-coated
      stents with zotarolimus-eluting stents for coronary revascularisation.
AB  - AIMS: Stents with a passive coating of titanium-nitride-oxide (TiNO) have been
      compared with Endeavor(r) zotarolimus-eluting stents (E-ZES) with regard to the
      primary endpoint of in-stent late lumen loss at six to eight months. The
      objective of the present analysis was to compare the long-term outcomes of TiNO
      stents with E-ZES up to five years of clinical follow-up. METHODS AND RESULTS: A
      total of 302 patients had been randomly allocated to treatment with TiNO or E
      ZES. Up to five years of follow-up, major adverse cardiac events (MACE), the
      composite of cardiac death, myocardial infarction, or clinically indicated target
      vessel revascularisation (TLR), were observed in 27.6% of patients treated with
      TiNO stents and 25.3% of patients treated with E-ZES (RR 1.13, 95% CI: 0.72-1.75,
      p=0.60), with the majority of events related to clinically indicated TVR (TiNO
      21.7% versus E-ZES 20.7%, RR 1.10, 95% CI: 0.67-1.81). There were no differences
      with respect to individual events including cardiac death, myocardial infarction
      or stent thrombosis between the two treatment arms up to five years of follow-up.
      A majority of patients remained free from angina throughout the entire study
      duration (TiNO 77.3% versus E-ZES 76.1%, p=0.92). CONCLUSIONS: Final five-year
      outcomes of the TIDE trial comparing TiNO stents with E-ZES revealed increased
      rates of MACE driven primarily by clinically indicated TVR. The TIDE trial is
      registered at ClinicalTrials.gov: NCT00492908.

PMID- 25572027
TI  - In silico structural analysis of group 3, 6 and 9 allergens from Dermatophagoides
      farinae.
AB  - Dermatophagoides farinae (Hughes; Acari: Pyroglyphidae) are the predominant
      source of dust mite allergens, which provoke allergic diseases, such as rhinitis,
      asthma and eczema. Of the 30 allergen groups produced by D. farinae, the Der f 3,
      Der f 6 and Der f 9 allergens are all trypsin-associated proteins, however little
      else is currently known about them. The present study used in silico tools to
      compare the amino acid sequences, and predict the secondary and tertiary
      structures of Der f 3, Der f 6 and Der f 9 allergens. Protein sequence alignment
      detected ~46% identity between Der f 3, Der f 6 and Der f 9. Furthermore, each
      protein was shown to contain three active sites and two highly conserved trypsin
      functional domains. Predictions of the secondary and tertiary structure
      identified alpha-helices, beta-sheets and random coils. The active sites of the
      three proteins appeared to fold onto each other in a three-dimensional model,
      constituting the active site of the enzyme. Epitope analysis demonstrated that
      Der f 3, Der f 6 and Der f 9 have 4-5 potential epitopes located in random coils,
      and the epitope sequences of Der f 3, Der f 6 and Der f 9 were shown to overlap
      in two domains (at amino acids 83-87 and 179-180); however the residues in these
      two domains were not identical. The present study aimed to conduct a biochemical
      and genetic analysis of these three allergens, and to potentially contribute to
      the development of vaccines for allergen-specific immunotherapy.

PMID- 25572029
TI  - Strong population structure of Schizopygopsis chengi and the origin of S. chengi
      baoxingensis revealed by mtDNA and microsatellite markers.
AB  - The Tibetan Plateau underwent dramatic geological and climatic changes, which had
      important implications for genetic divergence and population dynamics of
      freshwater fish populations. Fluctuations of the ecogeographical environment and
      major hydrographic formations might have promoted the formation of new subspecies
      or species. In order to understand the impact of plateau uplift on freshwater
      fish evolutionary history, we estimated the genetic diversity and population
      structure in two subspecies of Schizopygopsis chengi (S. c. chengi and S. c.
      baoxingensis) in upper Yangtze River in Tibetan Plateau area using mitochondrial
      DNA control region and eight microsatellite markers, which suggested that there
      was a close genetic relationship. S. chengi showed some significant genetic
      structure that did not correlate with geographic distance. Bayesian assignment
      tests indicated that S. chengi samples in the study could be divided into four
      populations: upstream population, midstream population, tributary population and
      S. c. baoxingensis population. S. c. chengi and S. c. baoxingensis showed
      significant genetic divergence. However, phylogenetic analysis, population
      structure analysis and historical gene flow estimation suggested that there was
      close genetic relationship between S. c. baoxingensis and the Dawei population
      which belongs to populations of S. c. chengi. The time that Dawei population
      suffered from a bottleneck and S. c. baoxingensis underwent population expansion
      was congruent with the last glacial period on the Tibetan Plateau. The results
      confirmed the hypothesis that the Dawei River and Baoxing River were once
      connected, and the Dawei and Baoxing populations originated from a single
      population, but were isolated into separate populations because of crustal
      movements and the Baoxing population evolved as S. c. baoxingensis. 

PMID- 25572028
TI  - Fibroblast growth factor 23 and sudden versus non-sudden cardiac death: the
      Cardiovascular Health Study.
AB  - BACKGROUND: Elevated fibroblast growth factor 23 (FGF-23) concentrations are
      associated with greater risk of cardiovascular events and mortality, especially
      among people with chronic kidney disease (CKD). Because individuals with CKD are
      at an increased risk of sudden cardiac death (SCD), we sought to understand
      whether FGF-23 level is a stronger risk factor for SCD versus non-SCD. STUDY
      DESIGN: Cohort study. SETTING & PARTICIPANTS: 3,244 participants 65 years or
      older in the community-based Cardiovascular Health Study. PREDICTOR: Plasma FGF
      23 concentrations. OUTCOMES: We assessed SCD and non-SCD in these analyses. SCD
      was adjudicated rigorously and was defined as a sudden pulseless condition of
      cardiac origin in a previously stable person occurring out of hospital or in the
      emergency department. MEASUREMENTS: We estimated associations of baseline FGF-23
      concentrations with SCD and non-SCD using Cox proportional hazards models after
      adjustment for demographics, cardiovascular risk factors, comorbid conditions,
      and kidney function. We also tested whether associations differed by CKD status.
      RESULTS: During a median follow-up of 8.1 years, there were 118 adjudicated SCD
      and 570 non-SCD events. After multivariable adjustment for demographics,
      cardiovascular risk factors, comorbid conditions, and parameters of kidney
      function, higher FGF-23 concentrations were an independent risk factor for non
      SCD (HR [per doubling], 1.17; 95% CI, 1.06-1.30). However, elevated FGF-23
      concentrations were not associated independently with SCD (HR [per doubling],
      1.07; 95% CI, 0.85-1.35). In stratified analysis by CKD status (36.5% of cohort),
      doubling of FGF-23 concentrations was associated independently with non-SCD
      (adjusted HR, 1.26; 95% CI, 1.10-1.45). A similar magnitude of association was
      observed between FGF-23 level and SCD in the CKD subgroup; however, it was not
      significant (HR, 1.20; 95% CI, 0.89-1.62). LIMITATIONS: Limited power to detect
      moderate-sized effects between FGF-23 level and SCD in both the primary and
      stratified analyses. CONCLUSIONS: In this population-based study, FGF-23 level
      elevations were associated independently with non-SCD. Among individuals with
      CKD, the associations between FGF-23 level and SCD and non-SCD were similar.

PMID- 25572030
TI  - NSAID enteropathy and bacteria: a complicated relationship.
AB  - The clinical significance of small intestinal damage caused by nonsteroidal anti
      inflammatory drugs (NSAIDs) remains under-appreciated. It occurs with greater
      frequency than the damage caused by these drugs in the upper gastrointestinal
      tract, but is much more difficult to diagnose and treat. Although the
      pathogenesis of NSAID enteropathy remains incompletely understood, it is clear
      that bacteria, bile, and the enterohepatic circulation of NSAIDs are all
      important factors. However, they are also interrelated with one another.
      Bacterial enzymes can affect the cytotoxicity of bile and are essential for
      enterohepatic circulation of NSAIDs. Gram-negative bacteria appear to be
      particularly important in the pathogenesis of NSAID enteropathy, possibly through
      release of endotoxin. Inhibitors of gastric acid secretion significantly
      aggravate NSAID enteropathy, and this effect is due to significant changes in the
      intestinal microbiome. Treatment with antibiotics can, in some circumstances,
      reduce the severity of NSAID enteropathy, but published results are inconsistent.
      Specific antibiotic-induced changes in the microbiota have not been causally
      linked to prevention of intestinal damage. Treatment with probiotics,
      particularly Bifidobacterium, Lactobacillus, and Faecalibacteriaum prausnitzii,
      has shown promising effects in animal models. Our studies suggest that these
      beneficial effects are due to colonization by the bacteria, rather than to
      products released by the bacteria. 

PMID- 25572031
TI  - Investigation of EBT2 and EBT3 films for proton dosimetry in the 4-20 MeV energy
      range.
AB  - Radiochromic films such as Gafchromic EBT2 or EBT3 films are widely used for dose
      determination in radiation therapy because they offer a superior spatial
      resolution compared to any other digital dosimetric 2D detector array. The
      possibility to detect steep dose gradients is not only attractive for intensity
      modulated radiation therapy with photons but also for intensity-modulated proton
      therapy. Their characteristic dose rate-independent response makes radiochromic
      films also attractive for dose determination in cell irradiation experiments
      using laser-driven ion accelerators, which are currently being investigated as
      future medical ion accelerators. However, when using these films in ion beams,
      the energy-dependent dose response in the vicinity of the Bragg peak has to be
      considered. In this work, the response of these films for low-energy protons is
      investigated. To allow for reproducible and background-free irradiation
      conditions, the films were exposed to mono-energetic protons from an
      electrostatic accelerator, in the 4-20 MeV energy range. For comparison,
      irradiation with clinical photons was also performed. It turned out that in
      general, EBT2 and EBT3 films show a comparable performance. For example, dose
      response curves for photons and protons with energies as low as 11 MeV show
      almost no differences. However, corrections are required for proton energies
      below 11 MeV. Care has to be taken when correction factors are related to an
      average LET from depth-dose measurements, because only the dose-averaged LET
      yields similar results as obtained in mono-energetic measurements. 

PMID- 25572033
TI  - 2014 National Institutes of Health Consensus Development Project on Criteria for
      Clinical Trials in Chronic Graft-versus-Host Disease: preface to the series.

PMID- 25572032
TI  - ABO mismatch is associated with increased nonrelapse mortality after allogeneic
      hematopoietic cell transplantation.
AB  - We evaluated ABO associated outcomes in 1737 patients who underwent allogeneic
      hematopoietic cell transplantation (allo-HCT) at Stanford University between
      January 1986 and July 2011. Grafts were 61% ABO matched, 18% major mismatched
      (MM), 17% minor MM, and 4% bidirectional MM. Median follow-up was 6 years. In
      multivariate analysis, overall survival (OS) was inferior in minor MM
      hematopoietic cell transplantations (median 2.1 versus 6.3 years; hazard ratio
      [HR], 1.56; 95% confidence interval [CI], 1.19 to 2.05; P = .001) in comparison
      with ABO-matched grafts. ABO minor MM was associated with an increase in early
      nonrelapse mortality (NRM) (18% versus 13%; HR, 1.48; 95% CI, 1.06 to 2.06; P =
      .02). In an independent Center for International Blood and Marrow Transplant
      Research (CIBMTR) analysis of 435 lymphoma patients receiving mobilized
      peripheral blood grafts, impairment of OS (HR, 1.55; 95% CI, 1.07 to 2.25; P =
      .021) and increased NRM (HR, 1.72; 95% CI, 1.11 to 2.68; P = .03) were observed
      in recipients of ABO minor-MM grafts. A second independent analysis of a CIBMTR
      data set including 5179 patients with acute myeloid leukemia and myelodysplastic
      syndrome identified a nonsignificant trend toward decreased OS in recipients of
      ABO minor-MM grafts and also found ABO major MM to be significantly associated
      with decreased OS (HR, 1.19; 95% CI, 1.08 to 1.31; P < .001) and increased NRM
      (HR, 1.23; 95% CI, 1.08 to 1.4; P = .002). ABO minor and major MM are risk
      factors for worse transplantation outcomes, although the associated hazards may
      not be uniform across different transplantation populations. Further study is
      warranted to determine which patient populations are at greatest risk, and
      whether this risk can be modified by anti-B cell therapy or other peri
      transplantation treatments.

PMID- 25572034
TI  - Inhibition of NMDAR reduces bladder hypertrophy and improves bladder function in
      cyclophosphamide induced cystitis.
AB  - PURPOSE: We examined the role of NMDAR in the regulation of bladder hypertrophy
      and function in a rat model of cyclophosphamide induced cystitis. MATERIALS AND
      METHODS: Cystitis was induced by intraperitoneal injection of cyclophosphamide
      (150 mg/kg body weight). NMDAR phosphorylation (activity) and signal transduction
      pathways were examined by direct measurement and by specific inhibitors in vivo.
      Bladder hypertrophy was measured by bladder weight/body weight and type I
      collagen expression. Bladder function was examined by metabolic recording,
      conscious cystometry and detrusor muscle strip contractility in response to
      carbachol. RESULTS: NMDAR activity measured by the phosphorylation level of the
      NMDAR1 (NR1) subunit was expressed in the spinal cord but not in the bladder at
      48 hours of cystitis. NMDAR inhibition with dizocilpine (MK-801) reduced the
      cystitis induced increment of bladder weight and type I collagen up-regulation in
      the bladder. NMDAR regulated type I collagen up-regulation was mediated by the
      PI3K/Akt pathway. NMDAR inhibition also attenuated cystitis induced urinary
      frequency measured by metabolic cage and cystometry. Cystitis decreased the
      responsiveness of detrusor muscle strips to carbachol, which was reversed by MK
      801 in vivo. Unlike MK-801 the NMDAR antagonist D-AP5, which could not block
      central NMDAR activity, had no effect on bladder hypertrophy, type I collagen up
      regulation or Akt activation caused by cystitis in the bladder. CONCLUSIONS:
      Findings suggest that NMDAR activity has a role in cystitis induced bladder
      hypertrophy and overactivity. NMDAR mediated Akt activation may underlie the
      mechanism of bladder dysfunction.

PMID- 25572035
TI  - Conditional probability of reclassification in an active surveillance program for
      prostate cancer.
AB  - PURPOSE: We evaluated the risk of prostate cancer reclassification by time on
      active surveillance. MATERIALS AND METHODS: From 1995 to 2014 we evaluated 557
      and 251 men at very low and at low risk, respectively, who were on active
      surveillance and compliant with prostate biopsies. Our primary study outcome was
      reclassification to higher risk disease by grade or extent. Freedom from
      reclassification was estimated using the Kaplan-Meier approach with adjustment
      for covariates using the Cox proportional hazards model. RESULTS: Within the
      first 2 years of surveillance patient survival free of reclassification by grade
      (p = 0.20) and by any biopsy criteria (p = 0.25) was similar in men with very low
      and low risk disease. After 2 years men with low risk disease were 2.4 times more
      likely to be diagnosed with a Gleason score of greater than 6 than men with very
      low risk disease (p = 0.002, HR 2.4, 95% CI 1.9-3.5). Additionally, beyond 2
      years on surveillance the risk of lifetime reclassification by grade and by any
      criteria decreased by 30% and 35% (each p <0.0001, HR 0.70, 95% CI 0.60-0.76 and
      HR 0.65, 95% CI 0.57-0.72, respectively) with each biopsy that showed no
      reclassification. CONCLUSIONS: The reclassification rate during surveillance is
      not equally distributed across time or risk groups. Due to misclassification at
      diagnosis the reclassification rate in very low and low risk groups is similar in
      the first 2 years but differs significantly beyond 2 years. The risk of
      reclassification decreases with time for each nonreclassifying biopsy beyond 2
      years.

PMID- 25572036
TI  - The sensory distribution in the dorsum of the hand: anatomical study with
      clinical implications.
AB  - The sensory distribution in the dorsum of the hand was investigated in 150
      formalin-fixed hands with the aim of outlining the most common innervation
      pattern of the superficial branch of the radial nerve (SBRN), dorsal branch of
      the ulnar nerve (DBUN) and the lateral antebrachial cutaneous nerve (LABCN).
      Although variable, the most common pattern found was SBRN innervation to the
      dorsal surface of the lateral 21/2 digits and DBUN innervation to the dorsal
      surface of the medial 21/2 digits. Dual innervation due to communicating branches
      or nerves overlapping was found in 41 cases. All-radial supply to the dorsum of
      the hand was found in ten cases. The LABCN was closely associated, and
      occasionally overlapped, with the SBRN. There were significant differences in the
      sensory distribution of the dorsum of the right and left hands of the same
      cadaver. The sensory distribution in the dorsum of the hand is variable; however,
      understanding the most common innervation pattern and appreciating the possible
      variations to this pattern is important to avoid errors in interpretation of
      conduction velocity studies, misdiagnosis of nerve pathology signs and symptoms
      and inappropriate treatments. 

PMID- 25572037
TI  - Lumbar plexus block surface landmarks as assessed by computed axial tomography in
      adult patients with scoliosis: a case series.
AB  - BACKGROUND AND OBJECTIVES: Lumbar plexus (LP) block is a common and useful
      regional anesthesia technique. Surface landmarks used to identify the LP in
      patients with healthy spines have been previously described, with the distance
      from the spinous process (SP) to the skin overlying the LP being approximately
      two-thirds the distance from the SP to the posterior superior iliac spine (PSIS)
      (SP-LP:SP-PSIS ratio). In scoliotic patients, rotation of the central neuraxis
      may make these surface landmarks unreliable, possibly leading to an increased
      block failure rate and an increased incidence of complications. The objective of
      the present study was to describe these surface landmarks of the LP in patients
      with scoliosis. METHODS: We selected 47 patients with known thoracolumbar
      scoliotic disease from our institution's radiology archives. We measured bony
      landmark geometry, Cobb angle, and the LP location and depth. Additionally, we
      calculated the SP-LP:SP-PSIS ratio for both the concave and convex sides.
      RESULTS: In scoliotic patients (31 females and 16 males), the median (range) Cobb
      angle was 23 (8-54) degrees. The LP depth was 7.5 (5.7-10.7) cm on the concave
      side of the scoliotic spine and 7.6 (5.4-10.8) cm on the convex side, while the
      distance from the SP-LP was 3.4 (1.9-4.7) cm on the concave side and 3.7 (2.4
      5.1) cm on the convex side. The SP-LP:SP-PSIS ratio was 0.61 (0.20-0.97) and 0.65
      (0.45-0.98) on the concave and convex sides, respectively. None of these
      distances were significantly different between sides. CONCLUSIONS: In patients
      with scoliotic disease of the spine, there is wide variability in the bony
      surface landmarks. The location of the LP is generally more medial than expected
      when compared with both modified and traditional landmarks. A review of the
      imaging studies and the pre-procedural ultrasound assessment of the anatomy
      should be considered prior to needle puncture.

PMID- 25572039
TI  - Wound-healing activity of an oligomer of alkannin/shikonin, isolated from root
      bark of Onosma echioides.
AB  - Root bark of Onosma echioides belonging to the family Boraginaceae is reported to
      be rich in naphthaquinones such as alkannins and shikonins. In this study, a
      dimer of alkannin/shikonin was isolated from the petroleum ether (60-80 C)
      extract of the bark, and the structure of the same was elucidated through
      spectral studies (UV, IR, NMR, MS and DEPT). The petroleum ether extract was
      found to contain 62.4% (w/w) of the dimer of alkannin/shikonin, and the compound
      is found to promote wound-healing process, when studied in the excision and
      incision wound models in albino rats.

PMID- 25572038
TI  - Chronic treatment with a tryptophan-rich protein hydrolysate improves emotional
      processing, mental energy levels and reaction time in middle-aged women.
AB  - Common pharmacological treatments of mood disorders aim to modulate serotonergic
      neurotransmission and enhance serotonin levels in the brain. Brain serotonin
      levels are dependent on the availability of its food-derived precursor essential
      amino acid tryptophan (Trp). We tested the hypothesis that delivery of Trp via
      food may serve as an alternative treatment, and examined the effects of a Trp
      rich, bioavailable dietary supplement from egg protein hydrolysate on cognitive
      and emotional functions, mood state, and sleep quality. In a randomised, placebo
      controlled, parallel trial, fifty-nine mentally and physically healthy women aged
      45-65 years received placebo (n 30) or the supplement (n 29) (both as 0.5 g twice
      per d) for 19 d. Emotional processing was significantly changed by
      supplementation, exhibiting a shift in bias away from negative stimuli. The
      results for the Affective Go/No-Go Task exhibited a slowing of responses to
      negative words, suggesting reduced attention to negative emotional stimuli. The
      results for the Facial Emotional Expression Rating Task also supported a shift
      away from attention to negative emotions and a bias towards happiness. An
      increase in arousal-like symptoms, labelled 'high energy', shorter reaction times
      and a slight benefit to sustained attention were observed in the treated
      subjects. Finally, when the supplement was taken 60-90 min before bedtime, a
      feeling of happiness before going to bed was consistently reported. In summary,
      daily consumption of a low-dose supplement containing bioavailable Trp may have
      beneficial effects on emotional and cognitive functions.

PMID- 25572040
TI  - Evaluation of renal function in the elderly, not as easy as it seems: a review.
AB  - In the elderly assessment of renal function by glomerular filtration rate
      estimation is crucial for diagnostic, therapeutic and prognostic purposes. Our
      aim is to illustrate the different formulas available and their respective
      advantages and disadvantages. 

PMID- 25572041
TI  - Deficits in distal radius bone strength, density and microstructure are
      associated with forearm fractures in girls: an HR-pQCT study.
AB  - Forearm fractures are common during growth. We studied bone strength in youth
      with a recent forearm fracture. In girls, suboptimal bone strength was associated
      with fractures. In boys, poor balance and physical inactivity may lead to
      fractures. Prospective studies will confirm these relationships and identify
      targets for prevention strategies. INTRODUCTION: The etiology of pediatric
      forearm fractures is unclear. Thus, we examined distal radius bone strength,
      microstructure, and density in children and adolescents with a recent low- or
      moderate-energy forearm fracture and those without forearm fractures. METHODS: We
      assessed the non-dominant (controls) and non-fractured (cases) distal radius (7%
      site) using high-resolution peripheral quantitative computed tomography (HR-pQCT)
      (Scanco Medical AG) in 270 participants (girls: cases n = 47, controls n = 61 and
      boys: cases n = 88, controls n = 74) aged 8-16 years. We assessed standard
      anthropometry, maturity, body composition (dual energy X-ray absorptiometry
      (DXA), Hologic QDR 4500 W) physical activity, and balance. We fit sex-specific
      logistic regression models for each bone outcome adjusting for maturity,
      ethnicity, height, and percent body fat. RESULTS: In girls, impaired bone
      strength (failure load, ultimate stress) and a high load-to-strength ratio were
      associated with low-energy fractures (odds ratios (OR) 2.8-4.3). Low total bone
      mineral density (Tt.BMD), bone volume ratio, trabecular thickness, and cortical
      BMD and thickness were also associated with low-energy fractures (ORs 2.0-7.0).
      In boys, low Tt.BMD, but not bone strength, was associated with low-energy
      fractures (OR = 1.8). Boys with low-energy fractures had poor balance and higher
      percent body fat compared with controls (p < 0.05). Boys with fractures (both
      types) were less active than controls (p < 0.05). CONCLUSIONS: Forearm fracture
      etiology appears to be sex-specific. In girls, deficits in bone strength are
      associated with fractures. In boys, a combination of poor balance, excess body
      fat, and low physical activity may lead to fractures. Prospective studies are
      needed to confirm these relationships and clarify targets for prevention
      strategies.

PMID- 25572042
TI  - Trends in the incidence of hip fracture in Gran Canaria, Canary Islands, Spain:
      2007-2011 versus 1989-1993.
AB  - Hip fracture incidence in the Canaries was studied in two 5-year periods (1989
      1993 and 2008-2011). The incidence in 2007-2011 was 24 % higher than in 1989, but
      did not differ between 2007-2011 and 1993. These findings suggest a trend to
      stabilize the incidence of hip fracture. INTRODUCTION: A dramatic increase in hip
      fractures between 1988 and 2002 was reported in Northern Spain. We performed the
      present study in Gran Canaria, the Canary Islands, to compare changes in the
      incidence of hip fracture between 1989-1993 and 2007-2011. METHODS: We recorded
      every osteoporotic hip fracture admitted to any hospital in Gran Canaria in the
      population 50 years of age or older. RESULTS: In 1989-1993, we collected 1175 hip
      fractures (72 % women; mean age 78.2 +/- 9.9 years), and the total incidence rate
      was 152.1 cases/100,000 population/year. In 2007-2011, we collected 2222 hip
      fracture cases (71 % women; mean age 79 +/- 9.8 years). The total incidence was
      180.9/100,000/year. A Poisson model showed that the incidence of fractures
      increased by 7.1 % (95 % CI = 3.1 %; 11.8 %) each year in 1989-1993, while there
      was no statistically significant variation (p = 0.515) during the period 2007
      2011. The incidence in 2007-2011 was 24 % higher than in 1989 (first year in the
      first period) but did not differ between 2007-2011 and 1993 (the last year of the
      first period). Incidence rates were 76.7 % (95 % CI = 63.9 %; 90.5 %) higher in
      women than in men, but the female/male ratio remained unchanged. The age-adjusted
      incidence of hip fractures increased by 7.3 % each year from 1989 to 1993. The
      proportions of trochanter and cervical fractures were similar in the two time
      periods, but the mean hospital stay was reduced from 11 days in 1989-1993 to 7
      days in 2007-2011. CONCLUSIONS: These findings suggest a trend to stabilize the
      incidence of hip fracture in the Canary Islands due to a decrease in men, while
      in women, the incidence increased.

PMID- 25572043
TI  - The social gradient of fractures at any skeletal site in men and women: data from
      the Geelong Osteoporosis Study Fracture Grid.
AB  - Age-specific and age-standardized associations between socioeconomic status (SES)
      and fractures in adults showed a social gradient of fracture, irrespective of
      fracture site. Compared to the highest SES, males in the lowest SES group had a
      sixfold increased odds for any fracture, whilst females had a twofold increased
      odds. INTRODUCTION: The effective identification of predisposing risk factors for
      fracture requires understanding any association with SES. These investigations
      should consider both sexes, span the adult age range and include any fractures.
      We investigated age- and sex-specific and age-standardized associations between
      SES and fractures at any skeletal site in Australians aged >= 50 years. METHODS:
      Incident fractures that occurred 2006-2007 for adults aged >= 50 years were
      identified from radiological reports extracted for the Barwon Statistical
      Division, in south-eastern Australia. SES was determined by cross-referencing
      residential addresses with Australian Bureau of Statistics census data and then
      categorized in quintiles. We compared frequencies of observed vs. expected
      fractures for SES quintiles using chi (2) comparison, calculated age-specific
      fracture incidence across SES and compared age-standardized fracture rates in SES
      quintile 1 to quintile 5. RESULTS: We identified 3943 incident fractures (69.4 %
      female); 47.4 % had occurred at major osteoporotic fracture (MOF) sites (hip,
      humerus, spine and forearm/wrist). Differences existed in observed vs. expected
      fractures across SES quintiles (p <= 0.001, sexes combined); all fractures showed
      an inverse association with SES (p <= 0.001, sexes combined). Compared to the
      highest SES quintile, individuals from the lowest SES quintile had between two to
      six times greater standardized fracture rates. CONCLUSIONS: Disadvantaged men and
      women have an increased fracture incidence compared to their less disadvantaged
      counterparts. The large differences in fracture rates between SES groups warrant
      further research into designing appropriate, targeted interventions for those
      demographics at most risk.

PMID- 25572044
TI  - Risk of osteoporotic fractures following stroke in older persons.
AB  - The aim of this study was to explore the increased risk of stroke survivors to
      different sustained osteoporotic fractures. We used hospital data and data on
      functional impairment. We found a higher risk in stroke survivors without
      functional impairment with the risk higher for lower than for upper extremity
      fractures. INTRODUCTION: Stroke survivors are at high risk of osteoporotic
      fractures due to frequent falls and an increased risk to develop osteoporosis.
      Data on their relative risk to sustain other than hip fractures is limited.
      Furthermore, the role of severe functional impairment on their fracture risk has
      not been considered yet. The aim of this study was to determine the relative risk
      of stroke survivors to sustain different osteoporotic fractures with regard to
      the presence of severe functional impairment. METHODS: Data from 2004 to 2009 of
      more than 1.2 million individuals aged 65 years or older and insured at a large
      German health insurance company were used for the analyses. Incident stroke and
      fractures were obtained from hospital diagnoses. Analyses were stratified by
      gender and information on severe functional impairment. Persons without preceding
      incident stroke were used as the reference group. Multistate models were used to
      estimate hazard ratios. RESULTS: Stroke survivors had a higher risk for
      fractures. However, a strong effect modification by functional impairment was
      apparent. Stroke survivors with functional impairment had no significantly
      increased risk for any fractures site compared to the corresponding reference
      group with functional impairment. In contrast, stroke survivors without
      functional impairment had a clearly and significantly increased fracture risk for
      most fracture sites. In these persons, the relative fracture risk for fractures
      of the lower extremities was higher than for fractures of the upper extremities.
      CONCLUSION: To evaluate the relative risk of stroke survivors for osteoporotic
      fractures, functional status appears to be a relevant parameter.

PMID- 25572045
TI  - The effect of supplementation with alkaline potassium salts on bone metabolism: a
      meta-analysis.
AB  - The role of acid-base metabolism in bone health is controversial. In this meta
      analysis, potassium bicarbonate and potassium citrate lowered urinary calcium and
      acid excretion and reduced the excretion of the bone resorption marker NTX. These
      salts may thus be beneficial to bone health by conserving bone mineral.
      INTRODUCTION: The role of acid-base homeostasis as a determinant of bone health
      and the contribution of supplemental alkali in promoting skeletal integrity
      remain a subject of debate. The objective of this study was, therefore, to
      conduct a meta-analysis to assess the effects of supplemental potassium
      bicarbonate (KHCO3) and potassium citrate (KCitr) on urinary calcium and acid
      excretion, markers of bone turnover and bone mineral density (BMD) and to compare
      their effects with that of potassium chloride (KCl). METHODS: A total of 14
      studies of the effect of alkaline potassium salts on calcium metabolism and bone
      health, identified by a systematic literature search, were analysed with Review
      Manager (Version 5; The Cochrane Collaboration) using a random-effects model.
      Authors were contacted to provide missing data as required. Results are presented
      as the standardised (SMD) or unstandardized mean difference (MD) (95 % confidence
      intervals). RESULTS: Urinary calcium excretion was lowered by intervention with
      both KHCO3 (P = 0.04) and KCitr (P = 0.01), as was net acid excretion (NAE) (P =
      0.002 for KHCO3 and P = 0.0008 for KCitr). Both salts significantly lowered the
      bone resorption marker NTX (P < 0.00001). There was no effect on bone formation
      markers or BMD. KHCO3 and KCitr lowered calcium excretion to a greater extent
      than did KCl. CONCLUSIONS: This meta-analysis confirms that supplementation with
      alkaline potassium salts leads to significant reduction in renal calcium
      excretion and acid excretion, compatible with the concept of increased buffering
      of hydrogen ions by raised circulating bicarbonate. The observed reduction in
      bone resorption indicates a potential benefit to bone health.

PMID- 25572046
TI  - Bisphosphonates and their influence on fracture healing: a systematic review.
AB  - Bisphosphonates are commonly used in osteoporosis, but concerns have been raised
      about possible negative effects on fracture healing. We systematically reviewed
      the literature and found that bisphosphonates significantly prolong union times
      of distal radius fractures but not femoral fractures. The timing of
      bisphosphonate introduction does not affect fracture union time. INTRODUCTION:
      Bisphosphonates are the most commonly prescribed drugs in patients suffering from
      and at higher risk of developing osteoporosis. However, concerns have been raised
      as to whether these drugs have a negative effect on fracture healing. The aim of
      this systematic review is to explore further these concerns. METHODS: A
      literature review was performed in line with the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All relevant articles
      found via MEDLINE, Cochrane, CINAHL, EMBASE and Google Scholar were screened.
      Studies with information on bisphosphonates' effect on fracture healing in humans
      were included and systematically reviewed. RESULTS: Patients with distal radius
      fractures on bisphosphonates had a significantly longer union time compared with
      controls, but not patients with femoral fractures. No correlation between timing
      of bisphosphonate introduction and union time for fractures was found. Although
      one study reported a higher humeral non-union associated with bisphosphonate
      introduction following the fracture, there was no evidence that bisphosphonate
      introduction, timing or dose resulted in a significant delay in union following
      other fractures. CONCLUSIONS: This systematic review has shown that
      bisphosphonates significantly prolong union times of distal radius fractures.
      Some clinical findings are in contrast with preclinical studies highlighting the
      need to develop better animal models to study osteoporosis, treatment and
      fracture healing. There is also a need for more well-constructed studies looking
      at the clinical effect of bisphosphonate on fracture healing in a large number of
      patients. These robust studies need to look at union time and non-union rates as
      a function of duration and dose of different bisphosphonates in different upper
      and lower limb fractures.

PMID- 25572047
TI  - Cost-effectiveness of hip protector use on a geriatric ward in Germany: a Markov
      model.
AB  - In this study, we determined the cost-effectiveness of hip protector use compared
      with no hip protector on a geriatric ward in Germany. From both the societal and
      the statutory health insurance (SHI) perspectives, the cost-effectiveness ratios
      for the provision of hip protectors were below <euro>12,000/quality-adjusted life
      year (QALY) even if unrelated costs in added life years were included.
      INTRODUCTION: The aim of this study is to determine the cost-effectiveness of the
      provision of hip protectors compared with no hip protectors on a geriatric ward
      in Germany. METHODS: A lifetime decision-analytic Markov model was developed.
      Costs were measured from the societal and from the statutory health insurance
      (SHI) perspectives and comprised direct medical, non-medical and unrelated costs
      in additional life years gained. Health outcomes were measured in terms of
      quality-adjusted life years (QALYs). To reflect several levels of uncertainty,
      first- and second-order Monte Carlo simulation (MCS) approaches were applied.
      RESULTS: Hip protector use compared with no hip protector results in savings
      (costs, -5.1/QALYs, 0.003) for the societal perspective. For the SHI perspective,
      the incremental cost-effectiveness ratio was <euro>4416 <euro>/QALY (costs,
      +13.4). If unrelated costs in life years gained were included, the cost
      effectiveness ratio increases to <euro>9794/QALY for the societal perspective and
      to <euro>11,426/QALY for the SHI perspective. In the MCS, for the societal
      perspective without unrelated costs, 47 % of simulations indicated hip protectors
      to be cost saving (i.e. lower costs and higher effects). CONCLUSION: Although the
      gain in QALYs due to the provision of providing hip protectors to patients on
      geriatric wards is small, all scenarios showed acceptable cost-effectiveness
      ratios or even savings.

PMID- 25572048
TI  - Association between fat mass, lean mass, and bone loss: the Dubbo Osteoporosis
      Epidemiology Study.
AB  - Lower body fat mass is a risk factor for bone loss at lumbar spine in
      postmenopausal women, but not in men. Body lean mass and fat mass were not
      associated with femoral neck bone loss in either gender. INTRODUCTION: Bone
      density and body mass are closely associated. Whole body lean mass (LM) and fat
      mass (FM) together account for approximately 95 % of body mass. Bone loss is
      associated with loss of body mass but which of the components of body mass (FM or
      LM) is related to bone loss is not well understood. Therefore, in this study, we
      sought to assess whether baseline FM or LM has predictive value for future
      relative rate of bone mineral density (BMD) changes (%/year). METHODS: The
      present population-based cohort study was part of the ongoing Dubbo Osteoporosis
      Epidemiology Study (DOES). BMD, FM, and LM were measured with dual energy X-ray
      absorptiometry (GE-LUNAR Corp, Madison, WI). BMD measurements were taken in
      approximately every 2 years between 2000 and 2010. We only included the
      participants with at least two BMD measurements at the femoral neck and lumbar
      spine. In total, 717 individuals (204 men and 513 women) aged 50 years or older
      were studied. RESULTS: Rate of bone loss at femoral neck and lumbar spine was
      faster in women than in men (all P < 0.01). In bivariable regression analysis,
      each 5 kg greater FM in women was associated with 0.4 %/year (P = 0.003) lower
      bone loss at lumbar spine. This magnitude of association remained virtually
      unchanged after adjusting for LM and/or other covariates (P = 0.03). After
      adjusting for covariates, variation of FM accounted for ~1.5 % total variation in
      lumbar spine bone loss. However, there was no significant association between FM
      and change in femoral neck BMD in either men or women. CONCLUSION: Lower FM was
      an independent but modest risk factor for greater bone loss at the lumbar spine
      in women but not in men. If further studies confirm our findings, FM can help
      predict lumbar spine bone loss in women.

PMID- 25572049
TI  - Can vitamin D metabolite measurements facilitate a "treat-to-target" paradigm to
      guide vitamin D supplementation?
AB  - Substantial variability exists in the serum 25(OH)D increase observed in response
      to vitamin D supplementation. Measurement of circulating cholecalciferol and
      24,25(OH)2D, as indicators of vitamin D absorption and degradation, respectively,
      account for approximately half of the variation in serum 25(OH)D observed
      following supplementation. INTRODUCTION: Vitamin D supplementation produces a
      variable response in serum 25(OH)D. This variability likely reflects, in part,
      differences in vitamin D absorption and/or degradation. Despite this variation in
      response, virtually all expert recommendations endorse a fixed vitamin D
      supplementation dose, an approach also used in most prospective studies. Such
      utilization of a single vitamin D dose does not assure attaining any pre
      specified target 25(OH)D level, thereby compromising clinical care and
      prospective supplementation trials. This study begins addressing this weakness by
      exploring the feasibility of vitamin D metabolite measurements to predict serum
      25(OH)D level attained following supplementation. METHODS: Ninety-one community
      dwelling postmenopausal women with baseline 25(OH)D of 10-30 ng/mL received oral
      vitamin D3, 2300 or 2500 IU, daily for 4-6 months. Serum 25(OH)D, cholecalciferol
      (D3), and 24,25(OH)2D were measured before and at the end of supplementation to
      determine if metabolite concentrations allow prediction of the 25(OH)D level
      attained. RESULTS: From baseline and follow-up data, we derived a multiple linear
      regression model predicting posttreatment 25(OH)D as follows: final 25(OH)D = 8.3
      + (1.05*initial 25(OH)D) - (7.7*initial 24,25(OH)2D) + (0.53*final D3) +
      (4.2*final 24,25(OH)2D). This model has an adjusted R(2) = 0.55, thus accounting
      for approximately half of the observed variance in the final 25(OH)D level.
      CONCLUSIONS: The contributions of circulating cholecalciferol and 24,25(OH)2D to
      this predictive model can be considered as indicators of intestinal absorption
      and clearance, respectively. This paradigm requires further study; it may allow
      efficient "treat-to-25(OH)D-target" strategies useful in optimizing prospective
      studies and clinical practice.

PMID- 25572050
TI  - Does fetal smoke exposure affect childhood bone mass? The Generation R Study.
AB  - We assessed the intrauterine influence of maternal smoking on childhood bone mass
      by comparing parental prenatal and postnatal smoking habits. We observed higher
      bone mass in children exposed to maternal smoking, explained by higher body
      weight. Maternal smoking or related lifestyle factors may affect childhood weight
      gain rather than skeletal growth. INTRODUCTION: Maternal smoking during pregnancy
      may adversely affect bone health in later life. By comparing the associations of
      maternal and paternal smoking and of prenatal and postnatal exposure with
      childhood bone measures, we aimed to explore whether the suggested association
      could be explained by fetal programming or reflects confounding by familial
      factors. METHODS: In 5565 mothers, fathers and children participating in a
      population-based prospective cohort study, parental smoking habits during
      pregnancy and current household smoking habits were assessed by postal
      questionnaires. Total body bone mineral content (BMC), bone area (BA) and bone
      mineral density (BMD) were measured by dual-energy X-ray absorptiometry (DXA) at
      the median age of 6.0 years (IQR 0.37). RESULTS: In confounder-adjusted models,
      maternal smoking during pregnancy was associated with a higher BMC of 11.6 g (95
      % confidence interval (CI) 5.6, 17.5), a larger BA of 9.7 cm(2) (95 % CI 3.0,
      16.4), a higher BMD of 6.7 g/cm(2) (95 % CI 2.4, 11.0) and a higher BMC of 5.4 g
      (95 % CI 1.3, 9.6) adjusted for BA of the child. Current weight turned out to
      mediate these associations. Among mothers who did not smoke, paternal smoking did
      not show evident associations with childhood bone measures. Also, household
      smoking practices during childhood were not associated with childhood bone
      measures. CONCLUSIONS: Our results do not support the hypothesis of fetal smoke
      exposure affecting childhood bone mass via intrauterine mechanisms. Maternal
      smoking or related lifestyle factors may affect childhood weight gain rather than
      skeletal growth.

PMID- 25572051
TI  - Regional variability in changes in the incidence of hip fracture in the Spanish
      population (2000-2012).
AB  - The objective is to analyse the evolution of the incidence of hip fracture in the
      female population of Spain from 2000 to 2012 and to establish the possible
      changes which may have been seen over this period of time, including the trends
      in the different regions of the country. INTRODUCTION: Fragility-related hip
      fractures are considered to be the fractures of greatest significance to public
      health due to their high degree of morbidity and mortality. The change in their
      incidence, both in absolute values and when adjusted for age, is the subject of
      debate. The objective of this article is to describe the changes in the rates of
      hip fracture in Spain by autonomous community between the years 2000 and 2012.
      METHODS: Using the data from the Spanish Minimum Basic Data Set, in which are all
      the recorded cases of women with a principal diagnosis of hip fracture, the
      incidence rates by age group and by autonomous community were obtained. Poisson
      distribution or negative binomial regressions were carried out to estimate the
      average annual change over the time period analysed. RESULTS: There have been
      statistically significant changes in the trends of rates of incidence for all age
      groups of women over 65 years of age. The annual reduction was 2.2% for women of
      65-74 years of age and less for those between 75 and 84. The rates of incidence
      for those over 85 increased annually by 0.58%. CONCLUSIONS: Hip fractures
      continue to increase in absolute numbers, although if the rates are adjusted for
      age, a downward trend is seen in certain age groups. These findings have various
      origins, although in the absence of great changes in population structure, we
      believe that drug treatments for osteoporosis may play a role. There is
      variability in the change in incidence of hip fractures in different parts of the
      country. Further studies are required to be able to identify the causes.

PMID- 25572052
TI  - Positive association between serum silicon levels and bone mineral density in
      female rats following oral silicon supplementation with monomethylsilanetriol.
AB  - Observational (epidemiological) studies suggest the positive association between
      dietary silicon intake and bone mineral density may be mediated by circulating
      estradiol level. Here, we report the results of a silicon supplementation study
      in rats that strongly support these observations and suggest an interaction
      between silicon and estradiol. INTRODUCTION: Epidemiological studies report
      strong positive associations between dietary silicon (Si) intake and bone mineral
      density (BMD) in premenopausal women and indicate that the association may be
      mediated by estradiol. We have tested this possibility in a mixed-gender rodent
      intervention study. METHODS: Tissue samples were obtained from three groups of 20
      week-old Sprague Dawley rats (five males and five females per group) that had
      been supplemented ad libitum for 90 days in their drinking water with (i) <0.1 mg
      Si/L (vehicle control), (ii) 115 mg Si/L (moderate dose) or (iii) 575 mg Si/L
      (high dose). All rats received conventional laboratory feed, whilst supplemental
      Si was in the form of monomethylsilanetriol, increasing dietary Si intakes by 18
      and 99 %, for the moderate- and high-dose groups, respectively. RESULTS: Fasting
      serum and tissue Si concentrations were increased with Si supplementation (p <
      0.05), regardless of gender. However, only for female rats was there (i) a trend
      for a dose-responsive increase in serum osteocalcin concentration with Si
      intervention and (ii) strong significant associations between serum Si
      concentrations and measures of bone quality (p < 0.01). Correlations were weaker
      or insignificant for tibia Si levels and absent for other serum or tibia
      elemental concentrations and bone quality measures. CONCLUSIONS: Our findings
      support the epidemiological observations that dietary Si positively impacts BMD
      in younger females, and this may be due to a Si-estradiol interaction. Moreover,
      these data suggest that the Si effect is mediated systemically, rather than
      through its incorporation into bone.

PMID- 25572053
TI  - Hypoxia-Inducible Factor 1-Alpha Regulates Cancer-Inhibitory Effect of Human
      Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) have been shown to be able to inhibit cancer cells
      growth. In this study, we investigate the role and the molecular mechanism of
      hypoxia-inducible factor 1-alpha (HIF-1alpha) in inhibition of cancer cell
      proliferation by human MSCs through depletion and overexpression of HIF-1alpha in
      human MSCs. We found that the cell culture medium from HIF-1alpha-depleted Z3
      cells significantly promotes breast cancer MCF-7 cell proliferation and colony
      formation. The expression of p21 is increased in MCF-7 cells, but p53 level
      remains unchanged. In contrast, the cultured medium from HIF-1alpha-overexpressed
      Z3 cells dramatically inhibits MCF-7 cell proliferation and colony formation. The
      expression of p21 is inhibited in MCF-7 cells, but p53 does not change. We
      conclude HIF-1alpha promotes inhibitory effect of human MCSs on breast cancer
      cell proliferation and colony formation. This process is tightly correlated with
      cell cycle protein p21 level in cancer cells.

PMID- 25572054
TI  - The Study of Different Approaches of Parecoxib Sodium Pretreatment on the
      Behavior of Rats with Neuropathic Pain.
AB  - Our objective is to analyze and observe the different administration routes of
      parecoxib sodium pretreatment on the behavioral improvement of rats with
      neuropathic pain to provide the preclinical data of parecoxib sodium on
      neuropathic pain treatment. 30 SD rats were randomly divided into five groups,
      including model group, sham operation group, intrathecal injection group (IT
      group), intraperitoneal injection group (IP group), and perineural infiltration
      group (PI group). The rats in model group and three parecoxib sodium pretreatment
      groups received spinal nerve ligation (SNL). Heat pain test and 50 % paw
      mechanical withdrawal threshold test (50 % PMWT) were use to assess the responses
      after parecoxib sodium pretreatment. 50 % PMWT results of right foot in five
      groups had no statistical difference (P > 0.05); 50 % PMWT results of left and
      right feet in three parecoxib sodium pretreatment groups were obviously higher
      than SNL group at different time points, which was statistically different (P <
      0.05); in comparison with three pretreatment groups, the data of left foot in IT
      group were obviously higher than PI group and IP group, and the comparison among
      three groups had significant difference (P < 0.05). However, the data of right
      foot had no significant difference among three groups (P > 0.05). Paw thermal
      withdrawal latency (PTWL) results of left and right feet in five groups had no
      significant difference before surgery (P > 0.05); after the establishment of
      neuropathic model, PTWL results in five groups were significantly decreased;
      however, PTWL results of left and right feet at 3 days after surgery in IT group
      were significantly higher than the two other pretreatment groups (P < 0.05); PTWL
      results of left and right feet at 7 and 14 days after surgery had no significant
      difference. Parecoxib sodium pretreatment can effectively improve the behaviors
      caused by neuropathic pain, and intrathecal injection is the most effective route
      of administration.

PMID- 25572055
TI  - McMurray Test: A Prediction of Arthroscopic Meniscectomy Outcomes in Patients
      with Knee Osteoarthritis.
AB  - The McMurray test is used to evaluate patients with meniscal tears of the knee.
      Analysis of the sensitivity and specificity of McMurray test and the correlation
      between McMurray sign and postoperative outcomes are helpful to screen the
      candidates for arthroscopic meniscectomy. The present study compares the results
      of McMurray test with arthroscopic examination in patients with knee
      osteoarthritis. We studied 149 patients diagnosed as meniscal lesion with
      osteoarthritis by radiology and had arthroscopic surgery. Our data show that
      positive McMurray sign implies good postoperative outcomes for the patients with
      meniscal tear associated with osteoarthritis. For patients with osteoarthritis,
      those whose positive McMurray signs are in line with their radiological findings
      indicate they are eligible candidates for arthroscopic meniscectomy. Our study
      suggests that McMurray sign can be used as an indication for both symptomatic
      meniscal tear and postoperative outcomes.

PMID- 25572056
TI  - Arthroscopic Characteristics of Normal and Discoid Meniscus Injury, and
      Efficiency of Recovery in Each Type of Meniscus Injury.
AB  - The aim of the study was to characterize under arthroscopy the features of normal
      and discoid meniscus injury, and to access the efficiency of recovery after
      operation. Data from 200 patients with meniscus injury who were admitted between
      May 2011 and October 2013 were collected. According to the type of meniscus
      injury, patients were divided into two groups: normal meniscus injury group (100
      patients) and discoid meniscus injury group (100 patients). Types of operation
      and characteristics of joint injury were compared between groups. Further, we
      compared recovery rates at 1-year postoperative follow-up, using Coriolis knee
      evaluation of joint functions. We observed five types meniscus tear in patients
      with normal meniscus: 40 % longitudinal, 32 % radial, 13 % horizontal, 8 %
      transverse, and 7 % complex. In discoid injury, these were, respectively, 5, 3,
      75, 7, and 10 %. Longitudinal, radial, and horizontal injury rates were
      significantly (p < 0.05) different between both groups. During operation, total,
      subtotal, and partial resections were utilized for normal meniscus injury in 10,
      27, 63 % of cases, and for discoid meniscus injury in 60, 25, and 15 %. Total
      resection was used significantly more frequently (p < 0.05) in discoid meniscus
      injury. A postoperative follow-up 1 year later revealed that the rates of
      excellent, good, and poor recovery were comparable between both normal and
      discoid meniscus injuries. With more frequent total resection for discoid
      meniscus injury and patients protecting their knee joints after the operation,
      the recovery rates are comparable between patients with normal or discoid
      meniscus injury. 

PMID- 25572057
TI  - Screening for Fetal Spina Bifida Aperta by the Ultrasound and Intracranial
      Translucency Examinations at 11-13(+6) Weeks of Gestation.
AB  - The objective of the study is to evaluate the clinical significance of screening
      for fetal spina bifida aperta by ultrasound examination and intracranial
      translucency (IT) measurement at 11-13(+6) weeks of gestation. About 1,479 women
      at 11-13(+6) weeks of gestation in our hospital in 2012 were included as
      observation group, and 1,608 women at 11-13(+6) weeks of gestation without IT
      measurement in 2011 was included as controls. Detection rates of fetal spina
      bifida aperta in two groups were compared. The translucency thickness between the
      brain stem and choroid plexus and crown-rump length (CRL) in mid-sagittal view of
      the fetal face was measured, and translucency thickness and CRL in fetuses with
      spina bifida and healthy ones were compared. Detection rate of fetal spina bifida
      aperta in observation group was significantly higher than that in control group
      (six cases in observation group and one case in control group, p = 0.046). IT
      thickness was significantly lower in fetuses with spina bifida aperta (0.01 +/-
      1.25 mm) than that in healthy ones (1.73 +/- 0.32 mm) (p < 0.001). There was
      positive correlation in healthy fetuses between IT thickness and CRL (r = 0.702,
      p < 0.001), but not in fetuses with spina bifida aperta (r = 0.001, p = 0.081).
      Ultrasound examination with IT measurement at 11-13(+6) weeks of gestation can be
      used to screen for fetal spina bifida aperta, and the reduction of IT thickness
      is an indicator of spina bifida aperta. 

PMID- 25572058
TI  - Regression Analysis of Non-iatrogenic Factors That Determine Adherence to
      Radiation Therapy.
AB  - The aim of this study is to explore non-medical factors that determine withdrawal
      from radiation therapy. Data from 2,643 patients who received radiotherapy in our
      Hospital from March 2010 to March 2012 were collected. Using gender, age, stage
      of the disease, Karnofsky score, aim of radiation therapy, therapy technique,
      vocation, medical insurance, and educational status as variables, 43 patients who
      terminated radiation therapy due to non-medical causes and 43 who completed the
      recommended course in the same period of time were, respectively, allocated to
      study and control groups. Univariate and 1:1 multivariate conditional logistic
      regression analyses were used to determine the risk facts for treatment
      withdrawal. Forty-three patients who withdrew from the therapy received at least
      one and maximally 26 therapy sessions (median of seven). A significant part of
      therapy withdrawals occurred during the first week and accounted for 37 % of
      therapy withdrawals. Univariate analysis showed that vocation, medical insurance,
      educational status, stage of the disease, Karnofsky score, aim, and technique of
      radiation therapy were significant determinants of therapy withdrawal.
      Furthermore, medical insurance status and stage of the disease were also found to
      be determinants in the multivariate regression analysis. Medical insurance and
      stage of the disease were found to be the major determinants that affect
      withdrawal from radiation therapy. 

PMID- 25572059
TI  - A Report on Safety Analysis of Tubeless Percutaneous Nephrolithotomy.
AB  - The objective is to evaluate clinical indications and safety of tubeless
      percutaneous nephrolithotomy (PCNL) for the treatment of stones in upper urinary
      tract. A total of 231 subjects accepted to undergo tubeless PCNL, both micro
      channel and standard operation were performed. After PCNL, renal gastrostomy tube
      was not placed also catheters and double-J stents were subsequently removed 3-5
      and 14-28 days, respectively. Primary PCNL resulted in stone clearance of 98.27
      %. There were five cases of postoperative hemorrhage with bleeding of about 500
      ml, which was stopped by keeping patients in bed and medication. Three cases had
      pleural injury and thoracentesis plus drainage was performed in one case. Other
      two cases did not receive any special treatment due to a small amount of pleural
      effusion. No urinary leakage, perineal hematoma, infection, and other
      complications were observed in both of these cases. One and three months check
      ups after discharge showed no recurrence of stones or perineal urinoma, and
      hydronephrosis were relieved in varying degrees. Thus, the application of
      tubeless PCNL is a safe and effective procedure for upper urinary tract calculi
      and the presence of stones was confirmed during operation showing good location
      with double-J stent and no obvious bleeding or damage. 

PMID- 25572060
TI  - The Use of Calcium Channel Blockers in the Treatment of Coronary Spasm and
      Atrioventricular Block.
AB  - Calcium channel blockers have been used in the treatment of coronary artery spasm
      for many years. However, there is insufficient knowledge about their application
      to treat atrioventricular block caused by coronary spasm. Clinical data of five
      patients who were diagnosed with coronary spasm caused by atrioventricular block
      and treated with calcium channel blockers were retrospectively assessed. The
      patients had varying degrees of atrioventricular block (confirmed by Holter ECG)
      and myocardial ischemia-like ST-T changes. Two patients were II type I AVB, two
      patients II type II AVB, and the remaining one patient was III AVB. All patients
      were all diagnosed with right coronary artery spasm by coronary angiography. The
      patients were treated with calcium channel blockers. No patient reported
      recurrence of chest pain or chest discomfort. On Holter ECG monitoring, no
      significant myocardial ischemia or atrioventricular block was seen. In
      conclusion, calcium channel blockers are effective and safe in the treatment of
      atrioventricular block caused by coronary spasm. 

PMID- 25572061
TI  - Anticonvulsant effectiveness and hemodynamic safety of midazolam in full-term
      infants treated with hypothermia.
AB  - BACKGROUND: Midazolam is used as an anticonvulsant in neonatology, including
      newborns with perinatal asphyxia treated with hypothermia. Hypothermia may affect
      the safety and effectiveness of midazolam in these patients. OBJECTIVES: The
      objective was to evaluate the anticonvulsant effectiveness and hemodynamic safety
      of midazolam in hypothermic newborns and to provide dosing guidance. METHODS:
      Hypothermic newborns with perinatal asphyxia and treated with midazolam were
      included. Effectiveness was studied using continuous amplitude-integrated
      electroencephalography. Hemodynamic safety was assessed using pharmacokinetic
      pharmacodynamic modeling with plasma samples and blood pressure recordings (mean
      arterial blood pressure) under hypothermia. RESULTS: No effect of therapeutic
      hypothermia on pharmacokinetics could be identified. Add-on seizure control with
      midazolam was limited (23% seizure control). An inverse relationship between the
      midazolam plasma concentration and mean arterial blood pressure could be
      identified. At least one hypotensive episode was experienced in 64%. The
      concomitant use of inotropes decreased midazolam clearance by 33%. CONCLUSIONS:
      Under therapeutic hypothermia, midazolam has limited add-on clinical
      anticonvulsant effectiveness after phenobarbital administration. Due to
      occurrence of hypotension requiring inotropic support, midazolam is less suitable
      as a second-line anticonvulsant drug under hypothermia.

PMID- 25572062
TI  - Development of twenty-nine polymorphic microsatellite loci from largemouth bronze
      gudgeon (Coreius guichenoti).

PMID- 25572063
TI  - Short tandem repeats in CdLS-causing genes: distribution and comparison.

PMID- 25572064
TI  - SNPs at exonic region of aquaporin-7 (AQP7) gene may affect semen quality
      parameters among crossbred bulls.

PMID- 25572065
TI  - New microsatellite markers for large yellow croaker (Pseudosciaena crocea) and
      cross-amplification in closely related species.

PMID- 25572066
TI  - Identification of SNPs in NPY and LEP and the association with food habit
      domestication traits in mandarin fish.

PMID- 25572067
TI  - Haplotype combination of the bovine PCSK1 gene sequence variants and association
      with growth traits in Jiaxian cattle.

PMID- 25572068
TI  - Dopamine receptor D4 (DRD4) gene polymorphism among Gaddi tribe of Himachal
      Pradesh.

PMID- 25572069
TI  - Fingerprinting of Fagaceae individuals using intermicrosatellite markers.

PMID- 25572070
TI  - Development of polymorphic microsatellite markers in Sardinella aurita by 5'
      anchored PCR technique.

PMID- 25572071
TI  - Microsatellite loci isolated from Chamaeleo chamaeleon.

PMID- 25572072
TI  - SNP marker analysis for validating the authenticity of Tunisian olive oil.

PMID- 25572073
TI  - AcuI identifies water buffalo CSN3 genotypes by RFLP analysis.

PMID- 25572074
TI  - Isolation and characterization of thirteen polymorphic microsatellite loci from
      black porgy (Acanthopagrus schlegeli).

PMID- 25572076
TI  - B-learning training in the certification of causes of death.
AB  - INTRODUCTION: An adequate certification of causes of death is essential for
      Public Health. The objective of this work is to improve the professional
      competence of medicine students and family doctors with regard to the
      certification of causes of death according to the international regulations of
      the WHO. METHODS: Intervention-formation, before and after design, addressed to
      students of Medicine in their last year (6th year), and Family Doctors and
      Interns. The blended learning or b-learning program consisted in an on-site
      seminar-workshop, plus basic information/documentation stored in an on-line
      platform, together with the preparation of Certificates of Causes of Death based
      on Clinical Histories of real cases. RESULTS: 308 students participated in the
      program. We observed an individual improvement in the professional competence in
      all certifications of death, which was significant in 3 out of 5 cases (it was
      not significant in a medical-legal case of violent death and the case of a
      pluripathological chronic patient). The intermediate causes improved in all
      cases. Most formal aspects of the certification improved with significant
      changes. In the group of 62 Family Doctors and interns who took part in the
      program there were improvements in the basic or underlying causes in 4 of the 5
      cases and improvements in the formal quality of the assessment, although less
      significantly than in students, because they started with better basal indexes in
      their certificates in the Before stage of the study. CONCLUSIONS: Blended
      learning training has shown to be effective in improving the professional
      competence, both in students of the Degree of Medicine and in practicing Family
      Doctors and Interns.

PMID- 25572075
TI  - Pentylenetetrazol-induced seizure-like behavior and neural hyperactivity in the
      medicinal leech.
AB  - This study examined the capacity of a known pro-epileptic drug, pentylenetetrazol
      (PTZ), to elicit seizure-like activity in the medicinal leech, Hirudo verbana.
      During in vivo experiments, PTZ elicited increased motor activity in a
      concentration-dependent manner with the highest concentration (10 mM) eliciting
      episodes of highly uncoordinated exploratory and swimming behavior. Co
      application of the anti-epileptic drug, phenytoin, failed to reduce the absolute
      amount of PTZ-induced motor behavior, but was able to prevent expression of
      abnormal exploratory and swimming behaviors. During in vitro experiments in which
      extracellular recordings of connective nerve activity were made, bath application
      of 1 MUM PTZ in Mg(2+)-free saline elicited a significant increase in spontaneous
      activity. This PTZ-induced increase in activity was completely inhibited by
      phenytoin. Interestingly, PTZ-induced hyperactivity was also blocked by co
      application of the endocannabinoid 2-arachidonoyl glycerol and the selective
      serotonin re-uptake inhibitor (SSRI) fluoxetine. These findings suggest that the
      leech can be a useful system in which to study potential anti-epileptic
      treatments.

PMID- 25572077
TI  - The Claims Management Committees trial: experience of an Italian hospital of the
      National Health System.
AB  - INTRODUCTION: In Italy, health care is mainly financed by earmarked central and
      regional taxes, with regions receiving their allocated share of resources from
      the National Health Fund. The Council of the Tuscany Region in 2009 began an
      experimentation aimed to enforce the extrajudicial conciliation. The Council
      established the Claims Management Committees (CMC) for civil liability in the
      Tuscan Health Service. The CMC trial provides that the damages are compensated
      directly by the hospital, removing the cost of liability insurance. The aim of
      this study is to collect and compare the liability-insurance-period and the CMC
      trial-period. MATERIALS AND METHODS: Data were derived from the management claims
      database of the Health Directorate of the Careggi Hospital in Florence between
      2006 and 2012. Two main periods are considered for the comparison of data: 2006
      2007-2008 during the insurance management and 2010-2011-2012 during the CMC
      trial. RESULTS: During the insurance management period, the total expenditure was
      equal to the ?14,846,334.44 paid in the 3-year period. The total expenditure
      during the CMC trial 3-years period was equal to ?7.076.370,75. Under the CMC
      management, we observed a marked decrease in the recourse to legal action in the
      face of a substantial maintenance of the number of claims opened for each year.
      The CMC trial showed a greater speed in setting claims for damages. DISCUSSION
      AND CONCLUSIONS: Under CMC management, a greater and more diligent efficiency is
      matched by a lower economic outlay. The use of the direct management of damage
      compensation may be an important tool for risk management, thus guaranteeing the
      recourse to targeted and appropriate interventions.

PMID- 25572078
TI  - Forensic considerations when dealing with incinerated human dental remains.
AB  - Establishing the human dental identification process relies upon sufficient post
      mortem data being recovered to allow for a meaningful comparison with ante-mortem
      records of the deceased person. Teeth are the most indestructible components of
      the human body and are structurally unique in their composition. They possess the
      highest resistance to most environmental effects like fire, desiccation,
      decomposition and prolonged immersion. In most natural as well as man-made
      disasters, teeth may provide the only means of positive identification of an
      otherwise unrecognizable body. It is imperative that dental evidence should not
      be destroyed through erroneous handling until appropriate radiographs,
      photographs, or impressions can be fabricated. Proper methods of physical
      stabilization of incinerated human dental remains should be followed. The
      maintenance of integrity of extremely fragile structures is crucial to the
      successful confirmation of identity. In such situations, the forensic dentist
      must stabilise these teeth before the fragile remains are transported to the
      mortuary to ensure preservation of possibly vital identification evidence. Thus,
      while dealing with any incinerated dental remains, a systematic approach must be
      followed through each stage of evaluation of incinerated dental remains to
      prevent the loss of potential dental evidence. This paper presents a composite
      review of various studies on incinerated human dental remains and discusses their
      impact on the process of human identification and suggests a step by step
      approach. 

PMID- 25572079
TI  - The source of haemorrhage in traumatic basal subarachnoid haemorrhage.
AB  - Traumatic basal subarachnoid haemorrhage (TBSH) following trauma to the head,
      face or neck is well-established as a cause of death; however it remains a
      heavily disputed topic as the site of vascular injury is difficult to identify.
      Whilst many regions within the vasculature of the head and neck have been
      proposed as more susceptible to rupture, the vertebral artery remains the focal
      point of many investigations. We present a retrospective case review of TBSH in
      our forensic centre at Forensic and Scientific Services in Brisbane, Australia,
      from 2003 to 2011. Thirteen cases of TBSH were found, one case excluded due to
      vasculopathy. All decedents were male, the majority of which were involved in an
      altercation receiving blows to the head, face, or neck and were unconscious at
      the scene. All victims were under the influence of alcohol, drugs, or a
      combination thereof. External examination revealed injuries to the head, face,
      and neck in all cases. Various combinations of further examination techniques
      were used during the post-mortem examination including brain and/or cervical
      spine retention, CT imaging, and angiography. Vascular injury was identified in
      eight of the twelve cases, all of which occurred intracranially, with seven
      involving the vertebral artery. Histology was most reliable in identifying the
      rupture site and angiography failed to reveal a rupture site. The added benefits
      of histology over angiography are the ability to identify the microscopic
      architecture of the tear and to diagnose vasculopathy that may have rendered the
      individual more susceptible to TBSH. 

PMID- 25572080
TI  - Letter to the Editor regarding the article by Roberts et al. published in volume
      26, August 2014.

PMID- 25572081
TI  - Occupational fatalities in Jordan.
AB  - OBJECTIVE: Occupational fatalities are a worldwide problem. Certain occupations
      pose a greater risk than others. Recent statistics on global occupational
      injuries and diseases that might lead to temporary or permanent disability and
      even worse might lead to death, are staggering. The purpose of this study was to
      estimate the death rates from occupational injuries in Jordan over a period of
      four years; to estimate occupational fatality rate that results from accidental
      injuries and identify the most risky concurrent occupations with the type of
      injuries, the age and nationality of the victims. METHOD: A total of 88 work
      related fatalities were admitted to three hospitals in Amman through 2008-2012
      and were examined by a forensic (occupational) physician at the time. They were
      categorized according to, age, nationality, occupation, type of injury and were
      all tested for toxic substances. RESULTS: The occupation with the most fatalities
      was construction (44%); falling from a height was the commonest type of accident
      (44%) and head injuries were the leading injury type (21.6%); 9.1% of the deaths
      were positive for alcohol. Moreover, 22.7% of deaths were between ages of 25-29.
      Consequently, the mean occupational fatality rate was 2 per 100.000 workers
      during 2008-2012. CONCLUSION: Constructions and other types of occupations are
      more extensive problems than what is usually anticipated, especially when safety
      precautions are not effective or implemented. They may cause injuries and death,
      which will have a socioeconomic burden on families, society, governments and
      industries. Not to mention the grief that is associated with the death of a
      worker at his work site to all concerned parties.

PMID- 25572082
TI  - Deaths due to hanging among adolescents - A 10-year retrospective study.
AB  - The present study was carried out to analyze various factors associated with
      death due to hanging among adolescents and to identify the areas of intervention
      for preventing such deaths. A retrospective study was carried out on 51 cases of
      adolescent deaths due to hanging, the autopsies of which were conducted by the
      Department of Forensic Medicine, Dr Shankarrao Chavan Government Medical College,
      Nanded, Maharashtra State (India), during the period between 1 January 2001 and
      31 December 2010. In the present study, death by hanging among the adolescent age
      group was most commonly suicidal (96.08%) in nature, and only two (3.92%) cases
      of deaths due to accidental hanging were observed. Of the total number of
      suicidal deaths due to hanging among adolescents, the majority (80.39%) were
      among the older adolescent (15-19 years) age group. Rope and clothing items were
      commonly used ligature materials for committing suicide by hanging. Females
      outnumbered male victims (M:F ratio 1:1.13) among adolescents, contrary to the
      male preponderance observed among victims of the older age group (M:F ratio
      1:0.44). Most of the suicidal deaths due to hanging (83.67%) among adolescents
      were observed at the victims' home. The predisposing and precipitating factors
      observed were domestic strife, examination-related stress, and physical and
      psychological illness. 

PMID- 25572083
TI  - Autopsy translates in Arabic to al-tashreeh. Could this term influence its
      acceptability?
AB  - It is not unusual for laypersons to object on the conduct of an autopsy of a
      loved one for fear of disfigurement or burial delays. In this paper, we discuss a
      new possible reason for objection among Arabic speaking communities related to
      the language. The Arabic word for autopsy is "al-tashreeh" which, when examining
      its other linguistic uses, might result in wrong inferences among laypersons. 

PMID- 25572084
TI  - The pathology of lethal exposure to the Riot Control Agents: towards a forensics
      based methodology for determining misuse.
AB  - The aim of this is to review deaths associated with the use of Riot Control
      Agents (RCAs) and to assess how the presenting pathologies is such cases may
      better inform cause of death conclusions upon autopsy. We also sought to present
      which additional steps should be added to the Minnesota protocol and the European
      harmonization of medico-legal autopsy rules in suspected cases of deaths
      associated with the use of RCAs. We included 10 lethal cases in our study. In
      three cases, RCAs were found to be the sole cause of death, in three cases RCAs
      were ruled a secondary cause of death due asphyxia or asthma subsequent to
      exposure to RCAs and in four cases RCAs were contributory factors to death. In
      three cases the responsible agents were identified as Chloroacetophenone (CN),
      Chlorobenzylidene malononitrile (CS) and Oleoresin capsicum (OC) and in the
      remaining 7 cases, the agent was OC alone. As there are no specific findings in
      suspected cases of death associated with RCA use, establishing cause of death and
      whether RCAs are the sole cause or only a contributory factor will be based on
      the elimination of other possible causes of death. For this reason, a
      specifically structured autopsy is essential. This specifically structured
      autopsy should contain basic principles of the Minnesota Protocol and the
      European harmonization of medico-legal autopsy rules with the following
      additional steps taken: examination of clothing, eyes, and skin; examination of
      pharyngeal, tracheobronchial, and eusophegeal mucosas; and a thorough recording
      of the steps taken by the party conducting the arrest, including other possible
      causes of in-custody death, as well as a detailed medical history of the
      deceased. 

PMID- 25572085
TI  - In vivo facial tissue depth for Canadian Mi'kmaq adults: a case study from Nova
      Scotia, Canada.
AB  - This study examines facial tissue depth in Canadian Mi'kmaq adults. Using
      ultrasound, measurements were taken at 19 landmarks on the faces of 152
      individuals aged 18-75 years old. The relationships between tissue thickness,
      age, and sex were investigated. A positive linear trend exists between tissue
      thickness and age for Mi'kmaq males and females at multiple landmarks. Seven
      landmarks show significant differences in facial tissue depth between males and
      females aged 18-34 years old; no landmarks show significant differences in facial
      tissue depth between males and females aged 35-45 years old and 46-55 years old.
      Significant differences were shown in facial tissue depth between Mi'kmaq and
      White Americans and Mi'kmaq and African Americans. These data can assist in 3-D
      facial reconstructions and aid in establishing the identity of unknown Mi'kmaq
      individuals. 

PMID- 25572086
TI  - Further comments to the discussion regarding the article: macroscopically
      detected female genital injury after consensual and non-consensual vaginal
      penetration.

PMID- 25572088
TI  - Value of 18F-FDG PET and PET/CT for evaluation of pediatric malignancies.
AB  - Successful management of solid tumors in children requires imaging tests for
      accurate disease detection, characterization, and treatment monitoring.
      Technologic developments aim toward the creation of integrated imaging approaches
      that provide a comprehensive diagnosis with a single visit. These integrated
      diagnostic tests not only are convenient for young patients but also save direct
      and indirect health-care costs by streamlining procedures, minimizing
      hospitalizations, and minimizing lost school or work time for children and their
      parents. (18)F-FDG PET/CT is a highly sensitive and specific imaging modality for
      whole-body evaluation of pediatric malignancies. However, recent concerns about
      ionizing radiation exposure have led to a search for alternative imaging methods,
      such as whole-body MR imaging and PET/MR. As we develop new approaches for tumor
      staging, it is important to understand current benchmarks. This review article
      will synthesize the current literature on (18)F-FDG PET/CT for tumor staging in
      children, summarizing questions that have been solved and providing an outlook on
      unsolved avenues. 

PMID- 25572087
TI  - Cortical laminar binding of PET amyloid and tau tracers in Alzheimer disease.
AB  - Neurofibrillary tau pathology and amyloid beta (Abeta) plaques, characteristic
      lesions of Alzheimer disease (AD), show different neocortical laminar
      distributions. Neurofibrillary-tangle tau pathology tends to be closer to the
      gray matter-white matter boundary, whereas Abeta is dispersed throughout the
      width of the cortical ribbon. METHODS: Using PET radiotracers for tau and Abeta
      lesions, we developed an image analysis tool to measure the distance of tracer
      positive voxels from the gray matter-white matter boundary. We studied 5 AD and 5
      healthy subjects with both (18)F-THK5117 (tau) and (11)C-Pittsburgh compound B
      (Abeta) PET. RESULTS: On average, tau-positive voxels were closer to the white
      matter than were Abeta-positive voxels. This effect was found for all AD subjects
      and for all regions, both before and after regionally adjusting for the
      nonspecific white matter binding of both tracers. The differential laminar
      pattern was validated through postmortem examination. CONCLUSION: Within cortical
      lamina, distance measures may be of value in testing PET tracers for their
      anatomic selectivity.

PMID- 25572090
TI  - Can the inflammatory response be evaluated using 18F-FDG within zones of
      microvascular obstruction after myocardial infarction?
AB  - Inflammation that occurs after acute myocardial infarction plays a pivotal role
      in healing by facilitating the creation of a supportive scar. (18)F-FDG, which is
      taken up avidly by macrophages, has been proposed as a marker of cell-based
      inflammation. However, its reliability as an accurate indicator of inflammation
      has not been established, particularly in the early postinfarction period when
      regional myocardial perfusion is often severely compromised. METHODS: Nine adult
      dogs underwent left anterior descending coronary occlusion with or without
      reperfusion. Animals were imaged between 7 and 21 d after infarction with PET/MR
      imaging after bolus injection of gadolinium-diethylenetriaminepentaacetic acid
      (DTPA), bolus injection of (18)F-FDG, bolus injection of (99)Tc-DTPA to simulate
      the distribution of gadolinium-DTPA (which represents its partition coefficient
      in well-perfused tissue), and injection of (111)In-labeled white blood cells 24 h
      earlier. After sacrifice, myocardial tissue concentrations of (18)F, (111)In, and
      (99)Tc were determined in a well counter. Linear regression analysis evaluated
      the relationships between the concentrations of (111)In and (18)F and the
      dependence of the ratio of (111)In/(18)F to the apparent distribution volume of
      (99m)Tc-DTPA. RESULTS: In 7 of 9 animals, (111)In increased as (18)F increased
      with the other 2 animals, showing weak negative slopes. With respect to the
      dependence of (111)In/(18)F with partition coefficient, 4 animals showed no
      dependence and 4 showed a weak positive slope, with 1 animal showing a negative
      slope. Further, in regions of extensive microvascular obstruction, (18)F
      significantly underestimated the extent of the presence of (111)In. CONCLUSION:
      In the early post-myocardial infarction period, (18)F-FDG PET imaging after a
      single bolus administration may underestimate the extent and degree of
      inflammation within regions of microvascular obstruction.

PMID- 25572091
TI  - Areas of high 18F-FDG uptake on preradiotherapy PET/CT identify preferential
      sites of local relapse after chemoradiotherapy for non-small cell lung cancer.
AB  - The high rates of failure in the radiotherapy target volume suggest that patients
      with stage II or III non-small cell lung cancer (NSCLC) should receive an
      increased total dose of radiotherapy. Areas of high (18)F-FDG uptake on
      preradiotherapy (18)F-FDG PET/CT have been reported to identify intratumor
      subvolumes at high risk of relapse after radiotherapy. We wanted to confirm these
      observations on a cohort of patients included in 3 sequential prospective
      studies. Our aim was to assess an appropriate threshold (percentage of maximum
      standardized uptake value [SUVmax]) to delineate subvolumes on staging (18)F-FDG
      PET/CT scans assuming that a smaller target volume would facilitate isotoxic
      radiotherapy dose escalation. METHODS: Thirty-nine patients with inoperable stage
      II or III NSCLC, treated with chemoradiation or with radiotherapy alone, were
      extracted from 3 prospective studies (ClinicalTrials.gov identifiers NCT01261585,
      NCT01261598, and RECF0645). All patients underwent (18)F-FDG PET/CT at initial
      staging, before radiotherapy, during radiotherapy, and during systematic follow
      up in a single institution. All (18)F-FDG PET/CT acquisitions were coregistered
      on the initial scan. Various subvolumes in the initial acquisition (30%, 40%,
      50%, 60%, 70%, 80%, and 90% SUVmax thresholds) and in the 3 subsequent
      acquisitions (40% and 90% SUVmax thresholds) were pasted on the initial scan and
      compared. RESULTS: Seventeen patients had a local relapse. The SUVmax measured
      during radiotherapy was significantly higher in locally relapsed tumors than in
      locally controlled tumors (mean, 6.8 vs. 4.6; P = 0.02). The subvolumes
      delineated on initial PET/CT scans with 70%-90% SUVmax thresholds were in good
      agreement with the recurrent volume at a 40% SUVmax threshold (common
      volume/baseline volume, 0.60-0.80). The subvolumes delineated on initial PET/CT
      scans with 30%-60% SUVmax thresholds were in good to excellent agreement with the
      core volume of the relapse (90% SUVmax threshold) (common volume/recurrent volume
      and overlap fraction indices, 0.60-0.93). The agreement was moderate (>0.51) when
      a 70% SUVmax threshold was used to delineate on initial PET/CT scans. CONCLUSION:
      High (18)F-FDG uptake areas on pretreatment PET/CT scans identify tumor
      subvolumes at greater risk of relapse in patients with NSCLC treated by
      concomitant chemoradiation. We propose a 70% SUVmax threshold to delineate areas
      of high (18)F-FDG uptake on initial PET/CT scans as the target volumes for
      potential radiotherapy dose escalation.

PMID- 25572092
TI  - Motion correction strategies for integrated PET/MR.
AB  - Integrated whole-body PET/MR facilitates the implementation of a broad variety of
      respiratory motion correction strategies, taking advantage of the strengths of
      both modalities. The goal of this study was the quantitative evaluation with
      clinical data of different MR- and PET-data-based motion correction strategies
      for integrated PET/MR. METHODS: The PET and MR data of 20 patients were
      simultaneously acquired for 10 min on an integrated PET/MR system after
      administration of (18)F-FDG or (68)Ga-DOTANOC. Respiratory traces recorded with a
      bellows were compared against MR self-gating signals and signals extracted from
      PET raw data with the sensitivity method, by applying principal component
      analysis (PCA) or Laplacian eigenmaps and by using a novel variation combining
      the former and either of the latter two. Gated sinograms and MR images were
      generated accordingly, followed by image registration to derive MR motion models.
      Corrected PET images were reconstructed by incorporating this information into
      the reconstruction. An optical flow algorithm was applied for PET-based motion
      correction. Gating and motion correction were evaluated by quantitative analysis
      of apparent tracer uptake, lesion volume, displacement, contrast, and signal-to
      noise ratio. RESULTS: The correlation between bellows- and MR-based signals was
      0.63 +/- 0.19, and that between MR and the sensitivity method was 0.52 +/- 0.26.
      Depending on the PET raw-data compression, the average correlation between MR and
      PCA ranged from 0.25 +/- 0.30 to 0.58 +/- 0.33, and the range was 0.25 +/- 0.30
      to 0.42 +/- 0.34 if Laplacian eigenmaps were applied. By combining the
      sensitivity method and PCA or Laplacian eigenmaps, the maximum average
      correlation to MR could be increased to 0.74 +/- 0.21 and 0.70 +/- 0.19,
      respectively. The selection of the best PET-based signal for each patient yielded
      an average correlation of 0.80 +/- 0.13 with MR. Using the best PET-based
      respiratory signal for gating, mean tracer uptake increased by 17 +/- 19% for
      gating, 13 +/- 10% for MR-based motion correction, and 18 +/- 15% for PET-based
      motion correction, compared with the static images. Lesion volumes were 76 +/-
      31%, 83 +/- 18%, and 74 +/- 22% of the sizes in the static images for gating, MR
      based motion correction, and PET-based motion correction, respectively.
      CONCLUSION: Respiratory traces extracted from MR and PET data are comparable to
      those based on external sensors. The proposed PET-driven gating method improved
      respiratory signals and overall stability. Consistent results from MR- and PET
      based correction methods enable more flexible PET/MR scan protocols while
      achieving higher PET image quality.

PMID- 25572094
TI  - Relationship between Alzheimer disease-like pattern of 18F-FDG and fasting plasma
      glucose levels in cognitively normal volunteers.
AB  - Increased plasma glucose (PG) levels can alter the cerebral distribution pattern
      of (18)F-FDG uptake and reduce (18)F-FDG uptake, especially in the precuneus. The
      (18)F-FDG distribution pattern in cognitively normal subjects is described as an
      Alzheimer disease (AD)-like pattern. The aim of this study was to determine the
      fasting PG levels that can reduce (18)F-FDG uptake in the precuneus. METHODS:
      Fifty-one cognitively normal volunteers (mean age +/- SD, 69.7 +/- 5.9 y)
      underwent (18)F-FDG PET scanning and were divided into 2 groups according to the
      level of fasting PG at the time of PET scanning: control (n = 31, 80 mg/dL <=
      fasting PG < 100 mg/dL) and impaired fasting glucose (IFG) (n = 20, 100 mg/dL <=
      fasting PG < 110 mg/dL). (18)F-FDG uptake was compared between the 2 groups using
      voxelwise analyses with a global normalization method and volume-of-interest
      (VOI)-based analyses. VOIs were placed on the precuneus, posterior cingulate, and
      visual cortex, and the ratio of the uptake value on the precuneus VOI to that on
      the visual cortex VOI (PreCne/VC ratios) and to that on the posterior cingulate
      VOI (PreCne/PostCin ratios) was calculated. RESULTS: Whole-brain voxelwise
      analyses showed that (18)F-FDG uptake in the precuneus was significantly lower in
      the IFG group (P < 0.05, familywise error rate-corrected) than in the control
      group. VOI analyses showed significantly lower PreCne/VC ratios (P = 0.002) and
      PreCne/PostCin ratios (P = 0.004) in the IFG group than in the control group.
      CONCLUSION: The present study confirmed that increased fasting PG levels decrease
      (18)F-FDG uptake, especially in the precuneus, as in the AD-like pattern.
      Furthermore, the study provided initial evidence that the AD-like pattern can
      appear even in an individual with a mildly higher level of fasting PG (100-110
      mg/dL).

PMID- 25572093
TI  - In vivo PET imaging demonstrates diminished microglial activation after
      fingolimod treatment in an animal model of multiple sclerosis.
AB  - There is a great need for the monitoring of microglial activation surrounding
      multiple sclerosis lesions because the activation of microglia is thought to
      drive widespread neuronal damage. Recently, second-generation PET radioligands
      that can reveal the extent of microglial activation by quantifying the increased
      expression of the 18-kDa translocator protein have been developed. Here, we
      investigate whether PET imaging can be used to demonstrate the reduction in
      microglial activation surrounding a chronic focal multiple sclerosis (MS)-like
      lesion after treatment with fingolimod, an established MS therapy. METHODS:
      Chronic focal experimental autoimmune encephalitis (EAE)-like lesions were
      induced in Lewis rats (n = 24) via stereotactic intrastriatal injection of heat
      killed bacillus Calmette-Guerin (BCG) and subsequent activation using an
      intradermal injection of BCG in complete Freund adjuvant. This process resulted
      in a delayed-type hypersensitivity (DTH)-like EAE lesion. The extent of
      neuroinflammation surrounding the lesion was measured using (18)F-GE180 as a PET
      radioligand. The imaging was performed before and after treatment with fingolimod
      (0.3 mg/kg/d by mouth, 28 d) or vehicle as a control. In addition to imaging,
      autoradiography and immunohistochemistry experiments were performed to verify the
      in vivo results. RESULTS: The chronic DTH EAE lesion led to increased ligand
      binding in the ipsilateral, compared with contralateral, hemisphere when PET
      imaging was performed with the translocator protein-binding radioligand (18)F
      GE180. Treatment with fingolimod led to a highly significant reduction in the
      binding potential, which could be demonstrated using both in vivo and ex vivo
      imaging (fingolimod vs. vehicle treatment, P < 0.0001). The area of increased
      (18)F-GE180 signal mapped closely to the area of activated microglial cells
      detected by immunohistochemistry. CONCLUSION: PET imaging, unlike MR imaging, can
      be used to visualize the microglial activation surrounding a chronic DTH EAE
      lesion. Importantly, the treatment effect of fingolimod can be monitored in vivo
      by measuring the degree of microglial activation surrounding the chronic DTH EAE
      lesion. This work gives promise for the introduction of new outcome measures
      applicable in treatment studies of progressive MS.

PMID- 25572095
TI  - Unexpected diversity of basidiomycetous endophytes in sapwood and leaves of
      Hevea.
AB  - Research on fungal endophytes has expanded dramatically in recent years, but
      little is known about the diversity and ecological roles of endophytic
      basidiomycetes. Here we report the analysis of 310 basidiomycetous endophytes
      isolated from wild and planted populations of the rubber tree genus, Hevea.
      Species accumulation curves were nonasymptotic, as in the majority of endophyte
      surveys, indicating that more sampling is needed to recover the true diversity of
      the community. One hundred eighteen OTUs were delimited, representing nine orders
      of Basidiomycota (Agaricales, Atheliales, Auriculariales, Cantharellales,
      Hymenochaetales, Polyporales, Russulales, Septobasidiales, Tremellales). The
      diversity of basidiomycetous endophytes found inhabiting wild populations of
      Hevea was comparable to that present in plantations. However, when samples were
      segregated by tissue type, sapwood of wild populations was found to contain a
      higher number of species than sapwood of planted trees. Seventy-five percent of
      isolates were members of the Polyporales, the majority in the phlebioid clade.
      Most of the species belong to clades known to cause a white-rot type of wood
      decay. Two species in the insect-associated genus Septobasidium were isolated.
      The most frequently isolated genera included Bjerkandera, Ceriporia,
      Phanerochaete, Phlebia, Rigidoporus, Tinctoporellus, Trametes (Polyporales),
      Peniophora, Stereum (Russulales) and Coprinellus (Agaricales), all of which have
      been reported as endophytes from a variety of hosts, across wide geographic
      locations. Literature records on the geographic distribution and host association
      of these genera revealed that their distribution and substrate affinity could be
      extended if the endophytic niche was investigated as part of fungal biodiversity
      surveys. 

PMID- 25572096
TI  - Fayochytriomyces, a new genus within Chytridiales.
AB  - Chytriomyces is a complex genus in Chytridiales. The morphological concept of the
      genus expanded as new taxa were added, and studies of zoospore ultrastructure and
      molecular phylogenies have revealed the genus to be polyphyletic. One problematic
      taxon is C. spinosus Fay, a distinctive species characterized by whorls of spines
      on the zoosporangium and a large accumulation of vesicle material beneath the
      operculum. With light-, scanning-electron and transmission-electron microscopy,
      we examined a culture (WJD186) isolated from a muck sample collected from a
      temporary forest pond. We also analyzed the D1-D2 variable domains of the nuc 28S
      rDNA (28S) sequences to confirm the phylogenetic placement of the species
      relative to the type of Chytriomyces, C. hyalinus Karling. The morphology of
      culture WJD186 is consistent with features Fay described for C. spinosus, and the
      zoospore ultrastructure is consistent with the Group I-type zoospore characters
      of Chytriomycetaceae (Chytridiales). In our molecular phylogeny C. spinosus does
      not group with the type of Chytriomyces. Consequently, we erect a new genus in
      Chytriomycetaceae and present the new combination Fayochytriomyces spinosus. 

PMID- 25572097
TI  - Sexual recombination in Aspergillus tubingensis.
AB  - Aspergillus tubingensis from section Nigri (black Aspergilli) is closely related
      to A. niger and is used extensively in the industrial production of enzymes and
      organic acids. We recently discovered sexual reproduction in A. tubingensis, and
      in this study we demonstrate that the progeny are products of meiosis. Progeny
      were obtained from six crosses involving five MAT1-1 strains and two MAT1-2
      strains. We examined three loci, including mating type (MAT), RNA polymerase II
      (RPB2) and beta-tubulin (BT2), and found that 84% (58/69) of progeny were
      recombinants. Recombination associated with sexual reproduction in A. tubingensis
      provides a new option for the genetic improvement of industrial strains for
      enzyme and organic acid production. 

PMID- 25572098
TI  - A new genus and family for the misclassified chytrid, Rhizophlyctis harderi.
AB  - A chytrid first discovered in Mediterranean sands and called Rhizophlyctis
      harderi was classified in the genus Rhizophlyctis based on its interbiotic
      vegetative thalli with multiple rhizoidal axes and resting thalli with tufts of
      rhizoid-like appendages. Developmental, electron microscopic and molecular
      analyses, however, have brought into question the proper placement of this
      chytrid. Because its original description was in German and not Latin, the name
      R. harderi is not validly published. We found that this chytrid produces three
      thallus forms that could place it in three different morpho-genera: Rhizophydium,
      Phlyctochytrium or Rhizophlyctis. The ultrastructural architecture of its
      zoospore is different from that of zoospores of Rhizophlyctis rosea, the type
      species for Rhizophlyctis, and shares zoospore ultrastructural characteristics
      with the Rhizophydiales. Zoospores of this chytrid exhibit a distinctive
      kinetosome-associated structure (KAS), a curved shield bridged to two of the
      kinetosomal triplets and a layered cap anterior to the kinetosome. Phylogenetic
      analyses of nuc rDNA also support the placement of this chytrid in the
      Rhizophydiales and not in the Rhizophlyctidales. Given its molecularly based
      phylogenetic placement and its distinctive zoospore architecture, we describe
      this chytrid in a new genus, Uebelmesseromyces, in the Rhizophydiales and erect
      Uebelmesseromycetaceae as a new family to accommodate it. 

PMID- 25572099
TI  - Detection of phytohormones in temperate forest fungi predicts consistent abscisic
      acid production and a common pathway for cytokinin biosynthesis.
AB  - The phytohormones, abscisic acid and cytokinin, once were thought to be present
      uniquely in plants, but increasing evidence suggests that these hormones are
      present in a wide variety of organisms. Few studies have examined fungi for the
      presence of these "plant" hormones or addressed whether their levels differ based
      on the nutrition mode of the fungus. This study examined 20 temperate forest
      fungi of differing nutritional modes (ectomycorrhizal, wood-rotting,
      saprotrophic). Abscisic acid and cytokinin were present in all fungi sampled;
      this indicated that the sampled fungi have the capacity to synthesize these two
      classes of phytohormones. Of the 27 cytokinins analyzed by HPLC-ESI MS/MS, seven
      were present in all fungi sampled. This suggested the existence of a common
      cytokinin metabolic pathway in fungi that does not vary among different
      nutritional modes. Predictions regarding the source of isopentenyl, cis-zeatin
      and methylthiol CK production stemming from the tRNA degradation pathway among
      fungi are discussed. 

PMID- 25572100
TI  - Taxonomic revision of Pseudolachnea and Pseudolachnella and establishment of
      Neopseudolachnella and Pseudodinemasporium gen. nov.
AB  - The taxonomy of Pseudolachnea and Pseudolachnella is controversial. Some authors
      have regarded them as congeneric, whereas others have considered them to be
      distinct genera differentiated merely on the number of conidial septa. A total of
      26 isolates of Pseudolachnea-like fungi were subjected to morphological
      examination and phylogenetic analyses of nuc rDNA internal transcribed spacers 1
      and 2 and partial 28S sequences and partial sequence of the translation
      elongation factor 1alpha gene. The results indicated that our materials should be
      classified in four genera: Pseudolachnea, Pseudolachnella, and two new genera,
      Neopseudolachnella and Pseudodinemasporium. Although the monophyly of both
      Pseudolachnea and Pseudolachnella was confirmed, it was concluded that
      differences observed in the conidiomatal structure, such as thickness of basal
      stroma and the excipulum, were more reliable for their circumscription, instead
      of conidial septation. Neopseudolachnella was similar to Pseudolachnea and
      Pseudolachnella in conidial morphology but was characterized by the conidiomata
      lacking an excipulum, unlike members of the latter two genera.
      Pseudodinemasporium bore conidia morphologically similar to those of
      Dinemasporium but was differentiated from the latter by the conidiomata, which
      was composed of a well developed peridial structure. A total of 12 new species,
      namely three in Neopseudolachnella (N. acutispora, N. magnispora, N. uniseptata),
      one in Pseudodinemasporium (P. fabiforme) and eight in Pseudolachnella (P.
      asymmetrica, P. botulispora, P. brevicoronata, P. campylospora, P. complanata, P.
      falcatispora, P. fusiformis and P. pachyderma) are described and illustrated. 

PMID- 25572103
TI  - Tuning macrocycles to design 'turn-on' fluorescence probes for manganese(II)
      sensing in live cells.
AB  - We tune the coordination environment of macrocyclic ligands to design two novel
      fluorescence sensors for Mn(2+). The BODIPY-based Mn(2+) sensor M1 affords an
      excellent, 52 fold, fluorescence 'turn-on' response despite the paramagnetic
      nature of Mn(2+). The lipophilic probe is cell-permeable and confocal imaging
      demonstrates that the sensor distinctly detects Mn(2+) within live cells. 

PMID- 25572102
TI  - Screening for pulmonary tuberculosis in type 2 diabetes elderly: a cross
      sectional study in a community hospital.
AB  - BACKGROUND: Tuberculosis is one of the major infectious diseases in Taiwan. It
      has an especially high prevalence in diabetes patients, in whom it is usually
      asymptomatic and are more likely to result in drug-resistant tuberculosis. The
      aim of the study was to aggressively screen high risk diabetic elderly, identify
      the prevalence of tuberculosis and its determinants. METHODS: Type 2 diabetes
      patients aged over 65 years were enrolled. They received chest X-rays, blood
      tests and the questionnaires to assess their medical history and symptoms.
      Suspicious cases were referred to the pulmonary or infectious disease outpatient
      clinics. Pulmonary tuberculosis was confirmed by sputum culture. Variables
      between groups were analyzed by Student t test, Chi-square test or Fisher's exact
      test. Risk factors were assessed using univariate logistic regression and
      multiple logistic regression. RESULTS: A total of 3,087 patients participated
      this screening program and 7 patients screened positive for pulmonary
      tuberculosis. Another 5 patients were being under treatment when participating
      screening program. The prevalence rate was 3.89 per thousand people. The patients
      with male gender, smoking, liver cirrhosis or subjective body weight loss were
      associated with an increased risk of tuberculosis significantly. Subjective body
      weight loss (OR: 6.635 [95% CI: 2.096-21.007]), liver cirrhosis (OR: 10.307 [95%
      CI: 2.108-50.395]) and history of smoking (OR: 3.981 [95% CI: 1.246-12.718]) are
      independent risk factors. Among all 73 patients with active tuberculosis or
      tuberculosis history, they tended to be male, lower body mass index (BMI), more
      smoking history, more alcohol consumption, more family history of tuberculosis,
      higher low density lipoprotein (LDL), and less hypertension. However, there was
      no significant difference in the glycated hemoglobin (HbA1c) levels between the
      tuberculosis group and non-tuberculosis group. CONCLUSIONS: Active screening
      program is helpful in detecting pulmonary tuberculosis in elderly diabetes
      patients. Subjective body weight loss, smoking and liver cirrhosis are
      independent risk factors.

PMID- 25572101
TI  - Three new species of Trichoderma with hyaline ascospores from China.
AB  - Collections of Trichoderma having hyaline ascospores from different areas of
      China were examined. Using combined analyses of morphological data, culture
      characters and phylogenetic information based on rDNA sequences of partial nuc
      translation elongation factor 1-alpha encoding gene (TEF1-alpha) and the gene
      encoding the second largest nuc RNA polymerase subunit (RPB2), three new species,
      Trichoderma applanatum, T. oligosporum and T. sinoluteum, were discovered and are
      described. Trichoderma applanatum produces continuous flat to pulvinate, white to
      cream stromata with dense orange or pale brown ostioles, and simple acremonium
      like to verticillium-like conidiophores, belongs to the Hypocreanum clade and is
      closely related to T. decipiens. Trichoderma oligosporum forms reddish brown
      stromata with a downy surface, hyaline conidia and gliocladium-like
      conidiophores, and is closely related to but distinct from T. crystalligenum in
      the Psychrophila clade. Trichoderma sinoluteum, as a member of the Polysporum
      clade, is characterized by pale yellow stromata, white pustulate conidiomata,
      pachybasium-like conidiophores, and hyaline conidia. Differences between the new
      species and their close relatives are discussed. 

PMID- 25572104
TI  - Oscillations in modulus in solutions of graphene oxide and reduced graphene oxide
      with grafted poly-N-isopropylamide.
AB  - In a material consisting of graphene oxide or reduced graphene oxide and poly-N
      isopropylamide (PNIPAM) in an aqueous solution, a new type of rheological
      behaviour is found. When subjecting the material to a short and relatively small
      deformation pulse, the modulus, which is observed by small deformations in the
      linear-viscoelastic or very slightly nonlinear range, oscillates with
      periodicities between 100 and several 1000 seconds; however, in many cases, it
      also increases systematically. The periodicity depends on the filler content and
      the sample preparation method (in situ polymerisation vs. blending). When
      subjecting the material to high nonlinear deformations (gamma0 = 100-300%), the
      resulting linear viscoelastic behaviour changes from a periodic oscillation to a
      quick recovery of the original data, followed by a decrease and a subsequent
      increase beyond the value of the modulus of the material prior to the deformation
      pulse. 

PMID- 25572105
TI  - Ester coupling reactions--an enduring challenge in the chemical synthesis of
      bioactive natural products.
AB  - In this review we investigate the use of complex ester fragment couplings within
      natural product total synthesis campaigns. We first outline the different
      biosynthetic and chemical strategies for performing complex ester couplings and
      on this mechanistic background we then present and discuss a collection of
      successful examples from the literature.

PMID- 25572107
TI  - Non-pharmacological approaches for pain relief during labour can improve maternal
      satisfaction with childbirth and reduce obstetric interventions.

PMID- 25572106
TI  - New, non-quinone fluorogeldanamycin derivatives strongly inhibit Hsp90.
AB  - Streptomyces hygroscopicus is a natural producer of geldanamycin. Mutasynthetic
      supplementation of an AHBA-blocked mutant with all possible monofluoro 3
      aminobenzoic acids provided new fluorogeldanamycins. These showed strong
      antiproliferative activity and inhibitory effects on human heat shock protein
      Hsp90. Binding to Hsp90 in the low nanomolar range was determined from molecular
      modelling, AFM analysis and by calorimetric studies. 

PMID- 25572108
TI  - Hepatic adrenal rest tumor: Diagnostic pitfall and proposed algorithms to prevent
      misdiagnosis as lipid-rich hepatocellular carcinoma.
AB  - We present a case of adrenal rest tumor of the liver in which differential
      diagnosis from lipid rich-hepatocellular carcinoma (HCC) was challenging. The
      patient was a 50-year-old woman in whom a 3-cm tumorous mass was discovered in
      segment 7 of the liver during computed tomography evaluation of a uterine
      leiomyoma. The preoperative diagnosis was HCC, and subsegmental liver resection
      was performed. The tumor appeared as a well-demarcated golden yellow nodule
      consisting of clear or partially eosinophilic cells arranged in a trabecular
      pattern. The initial impression of this lesion was that of clear cell type or
      lipid-rich type HCC because it stained positive for Hep Par1, but negative for
      arginase-1 and positive for CD56 which is one of the neuroendocrine markers. The
      lesion also stained positive for SF-1 and 3beta-HSD, both of which are markers of
      adrenocortical tissue. The final diagnosis was hepatic adrenal rest tumor.
      Hepatic adrenal rest tumor should be considered in the differential diagnosis of
      segment 7 tumor. A diagnostic algorithm that includes immunohistochemical
      staining for CD56 and arginase-1 is to rule out the possibility of lipid-rich
      HCC. 

PMID- 25572109
TI  - Modeling three-dimensional structure of two closely related Ni-Fe hydrogenases.
AB  - The results of homology modeling of HydSL, a NiFe-hydrogenase from purple sulfur
      bacterium Thiocapsa roseopersicina BBS, and deep-water bacterium Alteromonas
      macleodii deep ecotype are presented in this work. It is shown that the models
      have larger confidence level than earlier published ones; full-size models of
      these enzymes are presented for the first time. The C-end fragment of small
      subunit of T. roseopersicina hydrogenase is shown to have random orientation in
      relation to the main protein globule. The obtained models of this enzyme have a
      large number of ion pairs, as well as thermostable HydSL hydrogenase from
      Allochromatium vinosum, in contrast to thermostable HydSL hydrogenase from Alt.
      macleodii and thermolabile HydAB hydrogenase from Desulfovibrio vulgaris. The
      possible determinant of oxygen stability of studied hydrogenases could be the
      lack of several intramolecular tunnels. Hydrophobic and electrostatic surfaces
      were mapped in order to find out possible pathways of coupling hydrogenase to
      electron-transferring chains, as well as methods for construction of artificial
      photobiohydrogen-producing systems. 

PMID- 25572110
TI  - Compared decline of residual kidney function in patients treated with automated
      peritoneal dialysis and continuous ambulatory peritoneal dialysis: a multicenter
      study.
AB  - BACKGROUND: There is controversy concerning the compared rates of decline of
      residual kidney function (RKF) in patients treated with continuous ambulatory
      peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). OBJECTIVES
      AND METHOD: Following an observational, multicenter design, we studied 493
      patients initiating peritoneal dialysis (PD) in four different Spanish units. We
      explored the effect of the PD modality on the rate of decline of RKF and the
      probability of anuria during follow-up. We applied logistic regression for
      intention-to-treat analyses, and linear mixed models to explore time-dependent
      variables, excluding those affected by indication bias. MAIN RESULTS: Patients
      started on APD were younger and less comorbid than those initiated on CAPD.
      Baseline RKF was similar in both groups (p = 0.50). Eighty-seven patients changed
      their PD modality during follow-up. The following variables predicted a faster
      decline of RKF: higher (rate of decline) or lower (anuria) baseline RKF, younger
      age, proteinuria, nonprimary PD, use of PD solutions rich in glucose degradation
      products, higher blood pressure, and suffering peritonitis or cardiovascular
      events during follow-up. Overall, APD was not associated with a fast decline of
      RKF, but stratified analysis disclosed that patients with lower baseline RKF had
      an increased risk for this outcome when treated with this technique (HR: 2.26,
      95% CI: 1.09-4.82, p = 0.023). Moreover, the probability of anuria during follow
      up was overtly higher in APD patients (HR: 3.22, 95% CI: 1.25-6.69, p = 0.002).
      CONCLUSIONS: Starting PD patients directly on APD is associated with a faster
      decline of RKF and a higher risk of developing anuria than doing so on CAPD. This
      detrimental effect is more marked in patients initiating PD with lower levels of
      RKF.

PMID- 25572112
TI  - Temporomandibular joint disorders' impact on pain, function, and disability.
AB  - The aim of this study was to determine the association between more advanced
      stages of temporomandibular joint (TMJ) intra-articular disorders ("TMJ intra
      articular status"), representing a transition from normal joint structure to TMJ
      disc displacement with and without reduction (DDwR and DDwoR) to degenerative
      joint disease (DJD), and patient-reported outcomes of jaw pain, function, and
      disability ("TMD impact"). This cross-sectional study included 614 cases from the
      RDC/TMD Validation Project with at least one temporomandibular disorder (TMD)
      diagnosis. TMJ intra-articular status was determined by 3 blinded, calibrated
      radiologists using magnetic resonance imaging and computed tomography as one of
      normal joint structure, DDwR, DDwoR, or DJD, representing the subject's most
      advanced TMJ diagnosis. TMD impact was conceptualized as a latent variable
      consisting of 1) pain intensity (Characteristic Pain Index from the Graded
      Chronic Pain Scale [GCPS]), 2) jaw function (Jaw Functional Limitation Scale),
      and 3) disability (Disability Points from GCPS). A structural equation model
      estimated the association of TMJ intra-articular status with the latent measure
      TMD impact as a correlation coefficient in all TMD cases (n = 614) and in cases
      with a TMD pain diagnosis (n = 500). The correlations between TMJ intra-articular
      status and TMD impact were 0.05 (95% confidence interval [CI], -0.04 to 0.13) for
      all TMD cases and 0.07 (95% CI, -0.04 to 0.17) for cases with a pain diagnosis,
      which are neither statistically significant nor clinically relevant.
      Conceptualizing worsening of TMJ intra-articular disorders as 4 stages and
      characterizing impact from TMD as a composite of jaw pain, function, and
      disability, this cross-sectional study found no clinically significant
      association. Models of TMJ intra-articular status other than ours (normal
      structure -> DDwR -> DDwoR -> DJD) should be explored. 

PMID- 25572113
TI  - Erythema multiforme associated with Chlamydophila pneumoniae infection: a report
      of two cases and a mini-literature review.

PMID- 25572114
TI  - Open adjacencies and k-breaks: detecting simultaneous rearrangements in cancer
      genomes.
AB  - BACKGROUND: The evolution of a cancer genome has traditionally been described as
      a sequential accumulation of mutations - including chromosomal rearrangements -
      over a period of time. Recent research suggests, however, that numerous
      rearrangements may be acquired simultaneously during a single cataclysmic event,
      leading to the proposal of new mechanisms of rearrangement such as chromothripsis
      and chromoplexy. RESULTS: We introduce two measures, open adjacency rate (OAR)
      and copy-number asymmetry enrichment (CAE), that assess the prevalence of
      simultaneously formed breakpoints, or k-breaks with k >2, compared to the
      sequential accumulation of standard rearrangements, or 2-breaks. We apply the OAR
      and the CAE to genome sequencing data from 121 cancer genomes from two different
      studies. CONCLUSIONS: We find that the OAR and CAE correlate well with previous
      analyses of chromothripsis/chromoplexy but make differing predictions on a small
      subset of genomes. These results lend support to the existence of simultaneous
      rearrangements, but also demonstrate the difficulty of characterizing such
      rearrangements using different criterion.

PMID- 25572115
TI  - Influence of contact points on the performance of caries detection methods in
      approximal surfaces of primary molars: an in vivo study.
AB  - This in vivo study aimed to evaluate the influence of contact points on the
      approximal caries detection in primary molars, by comparing the performance of
      the DIAGNOdent pen and visual-tactile examination after tooth separation to
      bitewing radiography (BW). A total of 112 children were examined and 33 children
      were selected. In three periods (a, b, and c), 209 approximal surfaces were
      examined: (a) examiner 1 performed visual-tactile examination using the Nyvad
      criteria (EX1); examiner 2 used DIAGNOdent pen (LF1) and took BW; (b) 1 week
      later, after tooth separation, examiner 1 performed the second visual-tactile
      examination (EX2) and examiner 2 used DIAGNOdent again (LF2); (c) after tooth
      exfoliation, surfaces were directly examined using DIAGNOdent (LF3). Teeth were
      examined by computed microtomography as a reference standard. Analyses were based
      on diagnostic thresholds: D1: D 0 = health, D 1 -D 4 = disease; D2: D 0 , D 1 =
      health, D 2 -D 4 = disease; D3: D 0 -D 2 = health, D 3 , D 4 = disease. At D1,
      the highest sensitivity/specificity were observed for EX1 (1.00)/LF3 (0.68),
      respectively. At D2, the highest sensitivity/ specificity were observed for LF3
      (0.69)/BW (1.00), respectively. At D3, the highest sensitivity/specificity were
      observed for LF3 (0.78)/EX1, EX2 and BW (1.00). EX1 showed higher accuracy values
      than LF1, and EX2 showed similar values to LF2. We concluded that the visual
      tactile examination showed better results in detecting sound surfaces and
      approximal caries lesions without tooth separation. However, the effectiveness of
      approximal caries lesion detection of both methods was increased by the absence
      of contact points. Therefore, regardless of the method of detection, orthodontic
      separating elastics should be used as a complementary tool for the diagnosis of
      approximal noncavitated lesions in primary molars.

PMID- 25572116
TI  - Effects of a demand-led evidence briefing service on the uptake and use of
      research evidence by commissioners of health services: protocol for a controlled
      before and after study.
AB  - BACKGROUND: Clinical Commissioning Groups (CCGs) are mandated to use research
      evidence effectively to ensure optimum use of resources by the National Health
      Service (NHS), both in accelerating innovation and in stopping the use of less
      effective practices and models of service delivery. We intend to evaluate whether
      access to a demand-led evidence service improves uptake and use of research
      evidence by NHS commissioners compared with less intensive and less targeted
      alternatives. METHODS/DESIGN: This is a controlled before and after study
      involving CCGs in the North of England. Participating CCGs will receive one of
      three interventions to support the use of research evidence in their decision
      making: 1) consulting plus responsive push of tailored evidence; 2) consulting
      plus an unsolicited push of non-tailored evidence; or 3) standard service
      unsolicited push of non-tailored evidence. Our primary outcome will be changed at
      12 months from baseline of a CCGs ability to acquire, assess, adapt and apply
      research evidence to support decision-making. Secondary outcomes will measure
      individual clinical leads and managers' intentions to use research evidence in
      decision making. Documentary evidence of the use of the outputs of the service
      will be sought. A process evaluation will evaluate the nature and success of the
      interactions both within the sites and between commissioners and researchers
      delivering the service. DISCUSSION: The proposed research will generate new
      knowledge of direct relevance and value to the NHS. The findings will help to
      clarify which elements of the service are of value in promoting the use of
      research evidence. Those involved in NHS commissioning will be able to use the
      results to inform how best to build the infrastructure they need to acquire,
      assess, adapt and apply research evidence to support decision-making and to
      fulfil their statutory duties under the Health and Social Care Act.

PMID- 25572117
TI  - Polypyrrole shell@3D-Ni metal core structured electrodes for high-performance
      supercapacitors.
AB  - Three-dimensional (3D) nanometal films serving as current collectors have
      attracted much interest recently owing to their promising application in high
      performance supercapacitors. In the process of the electrochemical reaction, the
      3D structure can provide a short diffusion path for fast ion transport, and the
      highly conductive nanometal may serve as a backbone for facile electron transfer.
      In this work, a novel polypyrrole (PPy) shell@3D-Ni-core composite is developed
      to enhance the electrochemical performance of conventional PPy. With the
      introduction of a Ni metal core, the as-prepared material exhibits a high
      specific capacitance (726 F g(-1) at a charge/discharge rate of 1 A g(-1)), good
      rate capability (a decay of 33% in Csp with charge/discharge rates increasing
      from 1 to 20 A g(-1)), and high cycle stability (only a small decrease of 4.2% in
      Csp after 1000 cycles at a scan rate of 100 mV s(-1)). Furthermore, an aqueous
      symmetric supercapacitor device is fabricated by using the as-prepared composite
      as electrodes; the device demonstrates a high energy density (~21.2 Wh kg(-1))
      and superior long-term cycle ability (only 4.4% and 18.6% loss in Csp after 2000
      and 5000 cycles, respectively).

PMID- 25572119
TI  - Genomics, proteomics and metabolomics: their emerging roles in the discovery and
      validation of rheumatoid arthritis biomarkers.
AB  - Rheumatoid arthritis (RA) is an autoimmune inflammatory rheumatic disease which
      affects several organs and tissues, predominantly the synovial joints. Despite
      major advances, the aetiology of this disease is not completely understood.
      Although several biomarkers are routinely used in RA management and some of them
      can be detected even prior to the onset of the clinical disease, there is a high
      demand for novel biomarkers to further improve the early diagnosis of RA. The '
      omics' techniques that have emerged and have been developed in recent years have
      allowed researchers to improve their knowledge of the aetiopathology of RA. At
      the same time, advances in screening technologies offer an excellent opportunity
      to find new biomarkers potentially useful for early diagnosis, stratification of
      patients, and even prediction of a better response to a specific therapy. This
      review describes what is known about the methodologies used in the discovery of
      novel biomarkers in RA, along with the findings of these methodologies, with
      specific attention to recent advances in the fields of genomics, proteomics and
      metabolomics. 

PMID- 25572118
TI  - Silencing stathmin-modulating efficiency of chemotherapy for esophageal squamous
      cell cancer with paclitaxel.
AB  - Paclitaxel (PTX) is broadly considered the drug of choice for treating human
      esophageal squamous cell cancer (ESCC). However, PTX resistance often ultimately
      leads to treatment failure. stathmin, or Op18, is a ubiquitously expressed 19-kDa
      cytosolic phosphoprotein that can integrate various cellular regulatory signals.
      stathmin overexpression could lead to resistance to chemotherapeutic agents. In
      this study we investigated the effect of stathmin gene silencing, using small
      interfering RNA (stathmin siRNA), on the efficacy of PTX in ESCC. Transfection of
      stathmin siRNA could significantly inhibit stathmin mRNA and protein levels in
      ESCC cell lines EC9706 and Eca-109. The silencing of stathmin combined with PTX
      significantly inhibited the proliferation of EC9706 and Eca-109 cells, with a
      significantly higher proportion of cells at G2/M phase and this antiproliferative
      effect was accompanied by an increase in apoptosis rates and morphology changes
      of EC9706 and Eca-109. Thus, combined chemotherapeutic agent PTX and stathmin
      siRNA could potentially enhance the therapeutic outcomes of PTX in treating ESCC.

PMID- 25572120
TI  - Expression of oncogenic HMGN5 increases the sensitivity of prostate cancer cells
      to gemcitabine.
AB  - Prostate cancer is a leading cause of cancer-related death among men. Early
      diagnosis and treatment are successful against prostate cancer, yet the clinical
      treatment of advanced prostate cancer remains a challenge. Gemcitabine is used to
      treat a broad spectrum of solid tumors; however, the clinical response of
      prostate cancer patients to gemcitabine is limited. In the present study, we
      showed that HMGN5, a nucleosome binding protein that can unfold chromatin by
      binding to histone (H1), is overexpressed in prostate cancer cells and plays an
      oncogenic role in prostate cancer tumorigenesis and development by activating the
      MAPK signaling pathway. We also found that sensitivity of prostate cancer cells
      to gemcitabine was positively correlated with HMGN5 expression. Knockdown of
      HMGN5 expression reduced the sensitivity of PC-3 cells to gemcitabine, and
      ectopic HMGN5 expression in DU145 cells enhanced the sensitivity to gemcitabine.
      Gemcitabine decreased HMGN5 expression, consequently leading to inactivation of
      the MAPK signaling pathway and cleavage of the PARP protein. Finally, we showed
      that PC-3 cells acquire gemcitabine resistance by gradual loss of HMGN5
      expression. The present study suggests that HMGN5 is a potential biomarker for
      treating prostate cancer, and patients with a high level HMGN5 will benefit from
      gemcitabine treatment. 

PMID- 25572121
TI  - Musculoskeletal lesions and lameness in 121 horses with carpal sheath effusion
      (1999-2010).
AB  - Equine carpal sheath effusion has multiple etiologies. The purpose of this
      retrospective study was to describe the prevalence of distinct musculoskeletal
      lesions lameness in a sample of horses with a clinical diagnosis of carpal sheath
      effusion. A total of 121 horses met inclusion criteria. Seventy-four percent
      (89/121) of horses were lame at presentation; middle-aged (9-18 years, 80%) and
      older (> 18 years, 85%) horses were lame more frequently than young horses (< 9
      years, 44%). Ninety-three percent (113/121) were diagnosed with osseous and/or
      soft tissue abnormalities. Of these 113 horses, 10 exhibited osseous
      abnormalities, whereas 111 were diagnosed with soft tissue lesions. Eighty-four
      percent (93/111) of the soft tissue injuries extended from the caudodistal
      antebrachium to the palmar metacarpus. The superficial digital flexor tendon
      (98/111; 88%) and accessory ligament of the superficial digital flexor tendon
      (64/111; 58%) were the most commonly injured structures, with both structures
      affected in 41 (41/111; 37%) horses. Injuries within the caudodistal antebrachium
      included the superficial digital flexor musculotendinous junction (66), the
      accessory ligament of the superficial digital flexor tendon (64), and deep
      digital flexor muscle (21), in isolation or in combination with other structures.
      Increased echogenicity in the medial superficial digital flexor musculotendinous
      junction was detected in 40 horses and was significantly associated with
      increasing age (middle-aged, 19/40; old, 18/40). Findings from this study
      indicated that age should be taken into consideration for horses presented with
      carpal sheath effusion and that adjacent structures within the caudodistal
      antebrachium should be included in evaluations. 

PMID- 25572122
TI  - Phenotypic integration between antipredator behavior and camouflage pattern in
      juvenile sticklebacks.
AB  - Predation is a strong selective force that promotes the evolution of antipredator
      behaviors and camouflage in prey animals. However, the independent evolution of
      single traits cannot explain how observed phenotypic variations of these traits
      are maintained within populations. We studied genetic and phenotypic correlations
      between antipredator behaviors (shoaling and risk-taking) and morphology traits
      (pigmentation and size) in juvenile three-spined sticklebacks by using pedigree
      based quantitative genetic analysis to test phenotypic integration (or complex
      phenotype) as an evolutionary response to predation risk. Individuals with
      strongly melanized (i.e., camouflaged) phenotype and genotype were less sociable
      to conspecifics, but bolder during foraging under predation risk. Individuals
      with faster growing phenotype and genotype were bolder, and those with lager eyes
      were more fearful. These phenotypic integrations were not confounded with
      correlated plastic responses to predation risk because the phenotypes were
      measured in naive fish born in the laboratory, but originated from a natural
      population with predation pressure. Consistent selection for particular
      combinations of traits under predation pressure or pleiotropic genes might
      influence the maintenance of the genetic (co)variations and polymorphism in
      melanin color, growth trajectory, and behavior patterns. 

PMID- 25572123
TI  - Inhibitory effect and mechanisms of microRNA-146b-5p on the proliferation and
      metastatic potential of Caski human cervical cancer cells.
AB  - Cervical cancer is a common cause of cancer-associate mortality in females, and
      metastasis is strongly associated with failure of cervical cancer treatment.
      Previous studies have indicated that microRNA (miR)-146b-5p is involved in the
      inhibition of proliferation and metastasis of numerous human cancer types. The
      aim of the present study was to explore the inhibitory effect of miR-156b-5p on
      the proliferation and metastatic potential of Caski human cervical cancer cells,
      as well as to determine the mechanisms by which it proceeds. The results
      demonstrated that miR-146b-5p was able to inhibit the proliferative, invasive and
      adhesive potential and block the cell cycle progression of Caski human cervical
      cancer cells, as determined using MTS and transwell assays as well as flow
      cytometry. Furthermore, quantitative polymerase chain reaction and western blot
      analysis revealed that transfection with miR-146b-5p decreased the mRNA and
      protein expression levels of C-X-C chemokine receptor type 4, matrix
      metalloproteinase-2 and -9, c-Myc, cyclin D1 and human papilloma virus 16. In
      addition, the secretion levels of transforming growth factor-beta, monocyte
      chemoattractant protein-1 and tumor necrosis factor-alpha, the telomerase
      activity, the phosphorylation of c-Jun N-terminal protein kinase and protein
      kinase B and the transcriptional activities of nuclear factor-kappaB, signal
      transducer and activator of transcription-3 and -5 were reduced. However,
      increased levels of p27 and p53 were detected in the miR-146b-5p-overexpressing
      Caski cells. These results indicate that miR-146b-5p may be a potential
      therapeutic strategy for the treatment of cervical cancer through regulation of
      cell chemotaxis and the cell cycle.

PMID- 25572124
TI  - Critical evaluation and rate constants of chemoselective ligation reactions for
      stoichiometric conjugations in water.
AB  - Chemoselective ligation reactions have contributed immensely to the development
      of organic synthesis and chemical biology. However, the ligation of
      stoichiometric amounts of large molecules for applications such as protein
      protein conjugates is still challenging. Conjugation reactions need to be fast
      enough to proceed under dilute conditions and chemoselective in the presence of
      unprotected functional groups; the starting materials and products must be stable
      under the reaction conditions. To compare known ligation reactions for their
      suitability under these conditions, we determined the second-order rate constants
      of ligation reactions using peptide substrates with unprotected functional
      groups. The reaction conditions, the chemoselectivity of the reactions, and the
      stability of the starting materials and products were carefully evaluated. In
      some cases, the stability could be improved by modifying the substrate structure.
      These data obtained under the ligation conditions provide a useful guide to
      choose an appropriate ligation reaction for synthesis of large molecules by
      covalent ligation reactions of unprotected substrates in water. 

PMID- 25572125
TI  - Effect of local treatment with adipose tissue-derived mesenchymal stem cells in
      the early tumorigenesis of osteosarcoma.
AB  - There are conflicting data describing the effect of mesenchymal stem cells (MSCs)
      on tumorigenesis. The present study aimed to determine the survival rate and
      effect of adipose tissue-derived MSCs (ADMSCs) in tumor growth using
      bioluminescence imaging (BLI) and ultrasound (US) in an osteosarcoma xenograft
      model. Firefly luciferase-expressing ADMSCs combined with the osteosarcoma cell
      line UMR-106 in 4 different proportions (5, 10, 15 and 25%, named G1-G4,
      respectively) were xenografted into the right flanks of nude mice. The same
      number of UMR-106 cells was inoculated into the contralateral side of each mouse.
      Serial bioluminescence images were captured over 16 days to monitor the presence
      of ADMSCs in each group of 5 animals. The tumor volume was measured by ultra-high
      resolution US, and the tumor volume ratio (AMDSC mixed xenograft/control
      xenograft) was obtained to evaluate the effect of AMDSCs on tumor growth.
      Immunohistochemistry was performed to confirm the distribution of residual AMDSCs
      in the tumor. In G1, G2 and G3, the suppression of tumor growth by AMDSCs was
      noted in 2/5, 4/5 and 4/5 mice, respectively. However, accelerated tumor growth
      was noted in G4, which had the highest proportion of ADMSCs. The tumor volume
      ratio was significantly lower in G2 and G3 compared to G4, by Mann-Whitney U test
      (P=0.0159). Bioluminescence images demonstrated a serial decrement of the
      reporter gene for ADMSCs in the tumor mass without evidence of proliferation.
      Immunohistochemistry staining revealed minimal residual ADMSCs in the tumor
      periphery. Taken together, our data revealed that direct inoculation of ADMSCs
      into a tumor xenograft caused the death of the majority of ADMSCs in the tumor
      mass. Furthermore, relatively low proportions of ADMSCs suppressed the growth of
      osteosarcoma, while higher proportions showed a tumor-promoting effect.

PMID- 25572126
TI  - Performance improvement for dye-sensitized solar cells with Cone-calix[4]arene
      based dyes.

PMID- 25572128
TI  - Enzyme studies in combined carboxylase deficiency.

PMID- 25572127
TI  - Electrotunable lubricity with ionic liquid nanoscale films.
AB  - One of the main challenges in tribology is finding the way for an in situ control
      of friction without changing the lubricant. One of the ways for such control is
      via the application of electric fields. In this respect a promising new class of
      lubricants is ionic liquids, which are solvent-free electrolytes, and their
      properties should be most strongly affected by applied voltage. Based on a
      minimal physical model, our study elucidates the connection between the voltage
      effect on the structure of the ionic liquid layers and their lubricating
      properties. It reveals two mechanisms of variation of the friction force with the
      surface charge density, consistent with recent AFM measurements, namely via the
      (i) charge effect on normal and in-plane ordering in the film and (ii) swapping
      between anion and cation layers at the surfaces. We formulate conditions that
      would warrant low friction coefficients and prevent wear by resisting "squeezing
      out" of the liquid under compression. These results give a background for
      controllable variation of friction. 

PMID- 25572129
TI  - Role of c-Jun N-terminal kinase activation in apoptosis induced by removal of the
      growth factors.
AB  - Apoptosis plays a crucial role for generation of lymphocyte repertoire, clonal
      contraction, and elimination of virus-infected cells. Since IL-3-dependent pro-B
      cell line Baf-3 resulted in rapid induction of apoptotic cell death upon IL-3
      withdrawal, it would by very valuable for analysis of apoptosis induction by
      growth factor deprivation. First, we confirmed that Baf-3 cells underwent loss of
      mitochondrial membrane potential (DeltaPsim) and apoptosis in a time-dependent
      manner when they were cultured in the RPMI-1640 medium without IL-3. Induction of
      apoptosis and loss of DeltaPsim was determined by DiOC6 and annexin V staining
      method using flow cytometer, respectively. Deprivation of IL-3 induced
      upregulation of proapoptotic molecule Bax, in conjunction with slight down
      regulation of anti-apoptotic molecule Bcl-xL, which was assessed by Western
      blotting. Since Bcl-xL-overexpressing Baf-3 cells showed some resistance to IL-3
      deprivation, Bcl-xL prevents apoptosis induced by IL-3 withdrawal. Finally, a
      sustained JNK1 activation was observed prior to induction of apoptosis upon IL-3
      deprivation. Dominat-negative form of JNK1 and JNK inhibitor sp600125 partially
      inhibit the apoptosis upon IL-3 deprivation, suggesting that a sustained JNK1
      activation was involved in the induction of apoptosis. Together, IL-3 deprivation
      of IL-3-dependent cell line Baf-3 induces a sustained JNK1 activation, followed
      by a decline of the ratio of Bcl-xL to Bax, leading to loss of DCm, and finally
      apoptosis.

PMID- 25572130
TI  - A description of smallholder pig production systems in eastern Indonesia.
AB  - Pig farming is a common practice among smallholder farmers in Nusa Tenggara Timur
      province (NTT), eastern Indonesia. To understand their production systems a
      survey of smallholder pig farmers was conducted. Eighteen villages were randomly
      selected across West Timor, Flores and Sumba islands, and 289 pig farmers were
      interviewed. Information on pig management, biosecurity practices, pig movements
      and knowledge of pig health and disease, specifically classical swine fever was
      collected. The mean number of pigs per herd was 5.0 (not including piglets), and
      total marketable herd size (pigs>=two months of age) did not differ significantly
      between islands (P=0.215). Chickens (71%) and dogs (62%) were the most commonly
      kept animal species in addition to pigs. Pigs were mainly kept as a secondary
      income source (69%) and 83% of farmers owned at least one sow. Seventy-four
      percent (74%) of pigs were housed in a kandang (small bamboo pen) and 25% were
      tethered. Pig feeds were primarily locally sourced agricultural products (93%).
      The majority of farmers had no knowledge of classical swine fever (91%) and
      biosecurity practices were minimal. Forty-five percent (45%) reported to
      consuming a pig when it died and 74% failed to report cases of sick or dead pigs
      to appropriate authorities. Sixty-five percent (65%) of farmers reported that a
      veterinarian or animal health worker had never visited their village. Backyard
      slaughter was common practice (55%), with meat mainly used for home consumption
      (89%). Most (73%) farmers purchased pigs in order to raise the animal on their
      farm with 36% purchasing at least one pig within the last year. Predominantly
      fattener pigs (34%) were given as gifts for celebratory events, most commonly for
      funerals (32%), traditional ceremonies (27%) and marriages (10%). For improved
      productivity of this traditional low-input system, research incorporating farming
      training and improved knowledge on pig disease and biosecurity needs to be
      integrated with greater access to extension services. 

PMID- 25572131
TI  - A robust and conductive metal-impregnated graphene oxide membrane selectively
      separating organic vapors.
AB  - A small amount of Zn impregnated by ALD triggered enhancement of the mechanical
      as well as electrical properties of the graphene oxide (GO) membrane. In
      addition, the Zn-impregnated membranes selectively separated diverse organic
      vapors while maintaining high water permeability. 

PMID- 25572132
TI  - TGF-beta1 induces HMGA1 expression in human breast cancer cells: implications of
      the involvement of HMGA1 in TGF-beta signaling.
AB  - Transforming growth factor-beta1 (TGF-beta1) signaling and high mobility group A
      (HMGA1) are known to play essential roles in the progression of breast cancer by
      inducing epithelial-mesenchymal transition. However, the correlation between TGF
      beta1 and HMGA1 in breast cancer cell is not yet well understood. In this study,
      we determined the effects of TGF-beta1 on HMGA1 expression in breast cancer cells
      and examined the role of HMGA1 in breast cancer progression. Our results
      demonstrated that TGF-beta1 induced the expression of HMGA1 in both MCF-7 and MDA
      MB-231 breast cancer cells, as shown by RT-qPCR and immunofluorescence staining;
      however, the TGF-beta1-induced expression of HMGA was blocked by treatment of the
      cells with phosphatidylinositol-3 kinase (PI3K) signaling inhibitors. Moreover,
      the HMGA1 promoter activity was found to be activated by TGF-beta1 in the MCF-7
      and MDA-MB-231 cells and we found that specificity protein 1 (Sp1) was involved
      in the TGF-beta1-induced HMGA1 promoter activity, as shown by luciferase activity
      assay. Furthermore, the enforced expression of HMGA1 by transfection with a HMGA1
      promoter enhanced cellular oncogenic properties, including proliferation,
      migration and invasion, and a tissue microarray revealed that breast tumors
      expressing human epidermal growth factor receptor 2 (HER2) showed higher
      expression levels of HMGA1 (P=0.007). In addition, higher HMGA1 expression levels
      were also observed in the ductal breast cancer cases compared with the lobular
      breast cancer cases (P=0.000). These findings establish the first link between
      HMGA1 and TGF-beta1 in breast cancer, providing further evidence of the pivotal
      role of HMGA1 in breast cancer progression.

PMID- 25572135
TI  - Nanoscale interface engineering in ZnO twin nanorods for proposed phonon tunnel
      devices.
AB  - Zinc oxide twin nanorods, with two identical crystalline sections connected by an
      amorphous layer, were reproducibly grown using a simple one-step hydrothermal
      technique. The thickness of the amorphous layer between the crystalline segments
      was tunable with growth parameters, as confirmed by high resolution transmission
      electron microscopy. The photoluminescence spectra of these twin nanorods exhibit
      strong near band edge emission in the UV range, with convoluted phonon sidebands.
      De-convolution analyses of these spectra showed that the amorphous interlayers
      act as effective phonon barriers beyond a certain thickness. Such oriented grown
      individual crystalline-amorphous-crystalline structures may be a suitable test
      system for fundamental studies of phonon tunneling in the nanostructure. While
      physical vapor deposition techniques are seriously constrained in realizing
      crystalline-amorphous-crystalline structures, our results show the viability of
      engineering embedded interfaces via chemical routes. 

PMID- 25572133
TI  - Importance of circulating tumor cells in newly diagnosed colorectal cancer.
AB  - Presence of circulating tumor cells (CTC) is associated with poor prognosis in
      patients with metastatic colorectal cancer (CRC). The present study was conducted
      to determine if the presence of CTC prior to surgery and during follow-up in
      patients with newly diagnosed non-metastatic CRC can identify patients at risk
      for disease recurrence. In a prospective single center study 183 patients with
      newly diagnosed non-disseminated CRC, scheduled for surgery, were enrolled and
      followed-up for a median of 5.1 years. CTC were enumerated with the CellSearch
      system in 4 aliquots of 7.5 ml of blood before surgery and at several time-points
      during follow-up after surgery. The results showed that >=1 CTC/30 ml of blood
      were detected in 44 (24%) patients before surgery. Patients with CTC before
      surgery had a significant decrease in recurrence-free survival (RFS, log-rank
      test p=0.014) and colon cancer related survival (CCRS, p=0.002). The 5-year RFS
      dropped from 75 to 61% and the 5-year CCRS from 83 to 69% for patients with CTC
      before surgery. The presence of CTC and positive lymph nodes remained significant
      factors in multivariate analysis for recurrence-free survival (RFS).
      Surprisingly, the presence of CTC weeks after surgery was not significantly
      associated with RFS and CCRD whereas CTC 2-3 years after surgery was again
      significantly associated with RFS and CCRD. The presence of CTC in patients with
      stage I-III CRC before surgery is associated with a significant reduction in RFS
      and CCRS. These findings suggest a role of CTC detection to assess which patients
      need adjuvant treatment.

PMID- 25572134
TI  - Does maternal psychopathology increase the risk of pre-schooler obesity? A
      systematic review.
AB  - The preschool years may be a critical period for child obesity onset; however,
      literature examining obesity risk factors to date has largely focused on school
      aged children. Several links have been made between maternal depression and
      childhood obesity risks; however, other types of maternal psychopathology have
      been widely neglected. The aim of the present review was to systematically
      identify articles that examined relationships between maternal psychopathology
      variables, including depressive and anxiety symptoms, self-esteem and body
      dissatisfaction, and risks for pre-schooler obesity, including weight outcomes,
      physical activity and sedentary behaviour levels, and nutrition/diet variables.
      Twenty articles meeting review criteria were identified. Results showed positive
      associations between maternal depressive symptoms and increased risks for pre
      schooler obesity in the majority of studies. Results were inconsistent depending
      on the time at which depression was measured (i.e., antenatal, postnatal, in
      isolation or longitudinally). Anxiety and body dissatisfaction were only measured
      in single studies; however, both were linked to pre-schooler obesity risks; self
      esteem was not measured by any studies. We concluded that maternal depressive
      symptoms are important to consider when assessing risks for obesity in preschool
      aged children; however, more research is needed examining the impact of other
      facets of maternal psychopathology on obesity risk in pre-schoolers. 

PMID- 25572136
TI  - Quality of pathology reporting is crucial for cancer care and registration: a
      baseline assessment for breast cancers diagnosed in Belgium in 2008.
AB  - OBJECTIVES: Given the crucial role of pathology reporting in the management of
      breast cancers, we aimed to investigate the quality and variability of breast
      cancer pathology reporting in Belgium. MATERIALS AND METHODS: Detailed
      information on non-molecular and molecular parameters was retrieved from the
      pathology protocols available at the Belgian Cancer Registry for 10,007 breast
      cancers diagnosed in Belgium in 2008. RESULTS: Substantial underreporting was
      shown for several clinically relevant non-molecular parameters, such as
      lymphovascular invasion. High-volume laboratories performed only slightly better
      than others, and analyses at the individual laboratory level showed clear inter
      laboratory variability in reporting for all volume categories. Information on
      ER/PR and HER2 IHC was mentioned in respectively 91.7% and 90.8% of evaluative
      cases. HER2 ISH data were available for 78.5% of the cases judged to be 2+ for
      HER2 IHC. For cases with different specimens analysed, discordance between these
      specimens was highest for HER2, followed by PR. For HER2, results obtained from
      different laboratories were even less concordant. In addition, inter-laboratory
      differences were noted in the used ER/PR scoring systems, the proportion of ER
      /PR+ cases, and the relation between histological grade and ER/PR positivity.
      Data on Ki67 were only available for 43.8% of the investigated cases, and showed
      inconsistent use of cut-off values. CONCLUSION: Breast pathology reporting in
      Belgium in 2008 was suboptimal and showed considerable inter-laboratory
      variability. Synoptic reporting has been proposed as a facilitator towards
      increased reporting quality and harmonization, but the lack of aligned
      informatics remains a major hurdle in its concrete implementation.

PMID- 25572137
TI  - "With This You Can Meet Your Baby": Fetal Personhood and Audible Heartbeats in
      Oaxacan Public Health.
AB  - This article examines how amplified fetal heartbeats may be used to make claims
      about fetuses' social presence. These claims are supported by the Mexican Public
      Health system's selection of the maternal-child relationship as a key site of
      clinical intervention, intertwining medical and moral discourses. Drawing on the
      robust literature on cross-cultural propositions of "fetal personhood," this
      analysis uses ethnographic material from public health institutions in Oaxaca,
      Mexico, to explore how doctors use diagnostic technology to materialize fetuses
      for their patients. I argue that Spanish's epistemological distinction between
      saber (to have knowledge about) and conocer (to be acquainted with) is key to how
      diagnostic technologies may be deployed to make social claims. I use one doctor's
      attempts to use technology to shift her patient from saber to conocer as
      illustrative of underlying cultural logics about fetal embodiment and its proof.
      Focused on the under-theorized socio-medical deployment of audio fetal heartbeat
      technology, this article suggests that sound-in addition to sight-is a potent
      tool for constructing fetal personhood.

PMID- 25572139
TI  - Food intake assessment of elderly patients on hemodialysis.
AB  - OBJECTIVE: To investigate whether the dietary intake of elderly patients on
      hemodialysis (HD) is lower than that of elderly individuals with normal renal
      function. In addition, we also assessed whether the dietary intake of elderly on
      HD is lower on the dialysis day (DD) than on nondialysis days (non-DD). DESIGN: A
      cross-sectional and observational study including elderly on HD and non-chronic
      kidney disease (non-CKD) elderly. SUBJECTS: We assessed 54 noninstitutionalized
      elderly patients on HD (study group) and 47 non-CKD elderly (control group) aged
      >=60 years. MAIN OUTCOME MEASURES: All participants had their dietary intake
      assessed by 3-day food diaries. As a sensitivity analysis, we also assessed the
      dietary intake in the adequate reporters, which were identified when the ratio
      energy intake-to-estimated basal metabolic rate-was above 1.27 (Goldberg index).
      RESULTS: When comparing dietary intake between the study and control groups,
      adjusted for sex and underreporting, it was noted that only the intake of protein
      (beta: -9.9; P: .01) and phosphorus (beta: -104; P: .04) were significantly lower
      in the study group. In addition, when furthering the analysis in the study group
      by comparing DD with non-DD, it was observed that energy (18 +/- 7 vs. 21 +/- 8
      kcal/kg/day), protein (0.8 +/- 0.4 vs. 1.0 +/- 0.4 g/kg/day), lipids (41 +/- 20
      vs. 48 +/- 23 g/day), potassium (1371 +/- 587 vs. 1540 +/- 484 mg/day), and
      phosphorous intake (647 +/- 312 vs. 789 +/- 287 mg/day), but not carbohydrate
      (155 +/- 54 vs. 167 +/- 55 g/day) and calcium (470 +/- 345 vs. 518 +/- 333 g/day)
      were significantly lower on DDs than on non-DDs, respectively. CONCLUSIONS:
      Except for protein and phosphorous, energy and nutrient intake of elderly
      patients on HD are similar to that of non-CKD elderly. In addition, the dietary
      intake is lower on DDs, highlighting the importance of focusing efforts to
      improve nutritional intake mainly during the day of dialysis treatment.

PMID- 25572138
TI  - Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor
      knockout mice.
AB  - BACKGROUND AND PURPOSE: Antipsychotic drugs have been shown to modulate the
      expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the
      anti-atherogenic reverse cholesterol transport process, in vitro. Here we
      evaluated the potential of the typical antipsychotic drug haloperidol to modulate
      the cholesterol efflux function of macrophages in vitro and their susceptibility
      to atherosclerosis in vivo. EXPERIMENTAL APPROACH: Thioglycollate-elicited
      peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low
      density lipoprotein (LDL) receptor knockout mice were implanted with a
      haloperidol-containing pellet and subsequently fed a Western-type diet for 5
      weeks to induce the development of atherosclerotic lesions in vivo. KEY RESULTS:
      Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal
      macrophages. This coincided with a 30% decrease in the capacity of macrophages to
      efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the
      expression of ABCA1 (+51%) and other genes involved in reverse cholesterol
      transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No
      change in splenic ABCA1 expression was noted. However, the average size of the
      atherosclerotic size was significantly smaller (-31%) in the context of a mildly
      more atherogenic metabolic phenotype upon haloperidol treatment. More
      importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (
      28%) by peritoneal macrophages. CONCLUSIONS AND IMPLICATIONS: Haloperidol
      treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout
      mice to develop atherosclerotic lesions. Our findings suggest that the beneficial
      effect of haloperidol on atherosclerosis susceptibility can be attributed to its
      ability to inhibit macrophage chemotaxis.

PMID- 25572140
TI  - Evaluation of the safety, tolerability, and pharmacokinetics of a single bolus
      injection of daptomycin in healthy Japanese subjects.
AB  - This was a phase I double-blind, randomized, placebo-controlled, 2-period, single
      dose, crossover study in healthy Japanese subjects to evaluate the safety,
      tolerability, and pharmacokinetics of a single bolus injection of daptomycin.
      Twenty healthy subjects were randomized; 16 received a single intravenous (IV)
      administration of 6 mg/kg of daptomycin and 4 received a single intravenous
      administration of placebo (0.9% sodium chloride) by either bolus injection (10 s)
      or infusion (30 min) following an overnight fast in Periods 1 or 2. There was a
      minimum 5-day washout period from the administration in Period 1 to the
      administration in Period 2. Administration of a single bolus injection of
      daptomycin 6 mg/kg was generally well tolerated. The geometric mean ratios (GMRs)
      (90% confidence intervals [CIs]) for AUC0-infinity, AUC0-24 h, Cmax, and C24 h of
      daptomycin in plasma following bolus injection over 10 s relative to IV infusion
      over 30 min were 1.01 (1.00, 1.03), 1.02 (1.00, 1.03), 1.50 (1.41, 1.60) and 1.05
      (1.02, 1.08), respectively. Because no existing studies of this nature were
      available, Cmax following daptomycin 6 mg/kg/10 s multiple-dose bolus injections
      was simulated. It was estimated at 178 MUg/mL (upper limit) and was expected to
      be equal to or less than the confirmed Cmax in Japanese or non-Japanese healthy
      subjects following single- or multiple-dose IV infusion over 30 min. From the
      results of this study, daptomycin multiple-dose bolus injections over 10 s are
      expected well tolerated and to have similar Cmax values as IV infusion over 30
      min, thus offering potential clinical benefit. TRIAL REGISTRATION: Because this
      was a phase I trial in healthy subjects, the trial was not registered.

PMID- 25572141
TI  - [Intensity in the neurorehabilitation of spastic paresis].
AB  - Neurorestoration of motor command in spastic paresis requires a double action of
      stimulation and guidance of central nervous system plasticity. Beyond drug
      therapies, electrical stimulation and cell therapies, which may stimulate
      plasticity without precisely guiding it, two interventions seem capable of
      driving plasticity with a double stimulation and guidance component: the lesion
      itself (lesion-induced plasticity) and durable behavior modifications (behavior
      induced plasticity). Modern literature makes it clear that the intensity of the
      neuronal and physical training is a primary condition to foster behavior-induced
      plasticity. When it comes to working on movement, intensity can be achieved by
      the combination of two key components, one is the difficulty of the trained
      movement, the other is the number of repetitions or the daily duration of the
      practice. A number of recent studies shed light on promising recovery prospects,
      particularly using the emergence of new technologies such as robot-assisted
      therapy and concepts such as guided self-rehabilitation contracts. 

PMID- 25572142
TI  - [Paraplegia associated with cystinuria: A fortuitous association or direct
      relationship? A case report].

PMID- 25572143
TI  - Prognostic significance of lymph node metastases in small intestinal
      neuroendocrine tumors.
AB  - BACKGROUND/AIMS: Current staging guidelines for small intestinal neuroendocrine
      tumors (SI-NETs) differentiate between the presence (N1) and absence (N0) of
      lymph node (LN) metastases. However, the prognostic significance of the extent of
      LN involvement remains unknown. In this study, we used data from a population
      based cancer registry to examine whether involvement of a higher number of LNs is
      associated with worse survival. METHODS: We used the Surveillance, Epidemiology,
      and End Results (SEER) database to identify patients with histologically
      confirmed, surgically resected SI-NETS diagnosed between 1988 and 2010. Patients
      were classified into three groups by the LN ratio (number of positive LNs/number
      of total LNs examined, LNR): <=0.2, >0.2-0.5, and >0.5. We used the Kaplan-Meier
      method and Cox models to assess NET cancer-specific survival differences (up to
      10 years from diagnosis) according to LNR status. RESULTS: We identified 2,984
      surgically resected patients with stage IIIb (N1, M0) SI-NETs with detailed LN
      data. More than half of the NETs were located in the ileum. A higher LNR was
      significantly associated with worse NET cancer-specific survival (p < 0.0001).
      Ten-year NET-specific survival was 85, 77, and 74% for patients in the <=0.2,
      >0.2-0.5, and >0.5 LNR groups, respectively. In stratified analyses, higher LNR
      groups had worse survival only in early tumor (T1, T2) disease (p < 0.0001).
      CONCLUSIONS: The extent of LN involvement provides independent prognostic
      information on patients with LN-positive SI-NETs. This information may be used to
      identify patients at high risk of recurrence and inform decisions about the use
      of adjuvant therapy.

PMID- 25572144
TI  - The acute psychobiological impact of the intensive care experience on relatives.
AB  - There is a growing awareness amongst critical care practitioners that the impact
      of intensive care medicine extends beyond the patient to include the
      psychological impact on close family members. Several studies have addressed the
      needs of relatives within the intensive care context but the psychobiological
      impact of the experience has largely been ignored. Such impact is important in
      respect to health and well-being of the relative, with potential to influence
      patient recovery. The current feasibility study aimed to examine the acute
      psychobiological impact of the intensive care experience on relatives. Using a
      mixed methods approach, quantitative and qualitative data were collected
      simultaneously. Six relatives of patients admitted to the intensive care unit
      (ICU) of a District General Hospital, were assessed within 48 h of admission.
      Qualitative data were provided from semi-structured interviews analysed using
      interpretative phenomenological analysis. Quantitative data were collected using
      a range of standardised self-report questionnaires measuring coping responses,
      emotion, trauma symptoms and social support, and through sampling of diurnal
      salivary cortisol as a biomarker of stress. Four themes were identified from
      interview: the ICU environment, emotional responses, family relationships and
      support. Questionnaires identified high levels of anxiety, depression and trauma
      symptoms; the most commonly utilised coping techniques were acceptance, seeking
      support through advice and information, and substance use. Social support emerged
      as a key factor with focused inner circle support relating to family and ICU
      staff. Depressed mood and avoidance were linked to greater mean cortisol levels
      across the day. Greater social network and coping via self-distraction were
      related to lower evening cortisol, indicating them as protective factors in the
      ICU context. The experience of ICU has a psychological and physiological impact
      on relatives, suggesting the importance of identifying cost-effective
      interventions with evaluations of health benefits to both relatives and patients.

PMID- 25572145
TI  - Re-expression of HPV16 E2 in SiHa (human cervical cancer) cells potentiates NF
      kappaB activation induced by TNF-alpha concurrently increasing senescence and
      survival.
AB  - Re-expression of E2 in human papillomavirus (HPV) transformed tumour cells can
      induce apoptosis; however, some evidences also attribute an important role to E2
      in sustaining tumorigenesis. In the present paper, we studied the effects of
      tumour necrosis factor (TNF)-alpha-mediated NF-kappaB (nuclear factor kappa-light
      chain-enhancer of activated B-cells) activation on E2-induced senescence in HPV16
      integrated SiHa cells. The results show that E2 inhibits endogenous E6 gene
      expression and sensitizes SiHa cells to TNF-alpha-induced NF-kappaB activation.
      Under this condition there was an increase in the expression of senescent
      proteins p53, p21, p27 and p16 and senescence-associated (SA)-beta-galactosidase
      activity indicating that TNF-alpha augments E2-mediated senescence. Re-expression
      of E2 expression with TNF-alpha treatment resulted in an increase in the
      expression of anti-apoptotic Bcl2 (B-cell lymphoma 2) protein and other pro
      survival genes like cyclin D1 (cyc D1), survivin and hTERT (human telomerase
      reverse transcriptase). Concomitantly, E2 + TNF-alpha combination increased the
      survival of SiHa cells by positive changes in viability, proliferation and colony
      formation. E2-induced apoptotic tendency shifted towards senescence in presence
      of TNF-alpha by arresting the cells at both G0/G1 and G2/M phases, thus enhancing
      cell survival. Another observation in the present study is the significant up
      regulation of key senescence messaging factors regulated by NF-kappaB namely
      interleukin (IL)-6, IL-8, high-mobility group protein A (HMGA)1 and B (HMGB)1 in
      E2-transfected cells treated with TNF-alpha. Our data provide a mechanistic basis
      and a new insight for the role of TNF-alpha and E2 in linking cellular
      senescence, tumorigenesis and HPV re-infection. 

PMID- 25572146
TI  - A rule-based algorithm can output valid surgical strategies in the treatment of
      AIS.
AB  - BACKGROUND: Variability in surgical strategies for the treatment of adolescent
      idiopathic scoliosis (AIS) has been demonstrated despite the existence of
      classifications to guide selection of AIS curves to include in fusion. Decision
      trees and rule-based algorithms have demonstrated their potential to improve
      reliability of AIS classification because of their systematic approach and they
      have also been proposed in algorithms for selection of instrumentation levels in
      scoliosis. Our working hypothesis is that a rule-based algorithm with a knowledge
      base extracted from the literature can efficiently output surgical strategies
      alternatives for a given AIS case. Our objective is to develop a rule-based
      algorithm based on peer-reviewed literature to output alternative surgical
      strategies for approach and levels of fusion. METHODS: A literature search of all
      English Manuscripts published between 2000 and December 2009 with Pubmed and
      Google scholar electronic search using the following keywords: "adolescent
      idiopathic scoliosis" and "surgery" alternatively with "levels of fusion" or
      "approach". All returned abstracts were screened for contents that could contain
      rules to include in the knowledge base. A dataset of 1,556 AIS cases treated
      surgically was used to test the surgical strategy rule-based algorithm (SSRBA)
      and evaluate how many surgical treatments are covered by the algorithm. The SSRBA
      was programmed using Matlab. Descriptive statistic was used to evaluate the
      ability of the rule-based algorithm to cover all treatment alternatives. RESULTS:
      A SSRBA was successfully developed following Lenke classification's concept that
      the spine is divided into three curve segments [proximal thoracic (PT), main
      thoracic (MT) and thoracolumbar/lumbar (TL)]. Each of the 1,556 AIS patients in
      the dataset was ran through the SSRBA. It proposed an average of 3.78 (+/-2.06)
      surgical strategies per case. Overall, the SSRBA is able to match the treatment
      offered by the surgeon in approach and level of fusion 70 % of the time (with one
      vertebral level leeway). CONCLUSION: This study is to the author's knowledge the
      first attempt at proposing an algorithm to output all surgical alternatives for a
      given AIS case. It uses a rule-based algorithm with a knowledge base extracted
      from peer-reviewed literature in an area with great variability. When tested
      against a database of AIS patients treated surgically, the SSRBA developed has
      the ability to propose a surgical plan with respect to approach and levels of
      fusion that match the surgeon's plan in a great majority of cases. Since this
      SSRBA seems to output multiple valid surgical strategies, it could allow the
      comparisons of various strategies and the outcomes achieved in similar cases in
      large databases for a given case and guide surgical treatment.

PMID- 25572147
TI  - Cervical spine alignment following lumbar pedicle subtraction osteotomy for
      sagittal imbalance.
AB  - PURPOSE: The alignment of the cervical spine is of primary importance to maintain
      horizontal gaze and contributes to the functional outcome of patients. Cervical
      spine alignment after correction of major sagittal imbalance has rarely been
      reported in the literature. METHODS: Retrospective review of 31 consecutive
      patients with sagittal plane deformities operated by lumbar pedicle subtraction
      osteotomy. Pre-operative and 3 months post-operative full-length radiographies
      were analyzed for spinopelvic and cervical-specific parameters. RESULTS: There
      was a significant increase in lumbar lordosis (LL), thoracic kyphosis, and sacral
      slope. There was also a significant decrease in pelvic tilt, pelvic incidence
      minus LL, knee flexion and sagittal vertical axis. The cervical analysis revealed
      that there was no significant difference between pre- and post-operative global
      cervical lordosis (CL) angle and external auditory meatus (EAM) tilt. There was a
      significant decrease of C7 slope and distal CL, while a significant increase in
      occipito-C2 (OC2) angle was observed. CONCLUSION: LL restoration decreased the
      need of compensation at the pelvis and thoracic spine. The distal CL and C7 slope
      decreased because there was no need for compensation at this level after the
      surgery, but the proximal cervical spine takes a slightly flexed position to
      maintain horizontal sight. EAM tilt measures the head position toward C7, and is
      close to 0 degrees  even in severe cases. Changes of this parameter after surgery
      are insignificant, probably due to the balance between upper and lower cervical
      segments; when one of these segments shifts backward the other shifts forward and
      the result is a balanced head over C7.

PMID- 25572148
TI  - Post-trauma scoliosis after conservative treatment of thoracolumbar spinal
      fracture in children and adolescents: results in 48 patients.
AB  - PURPOSE: Authors examined a case series of patients younger than 18 years old who
      had sustained a traumatic thoracolumbar spine fracture to evaluate radiological
      and clinical findings of coronal spinal balance, after conservative treatment.
      METHODS: From 1996 to 2014, a tricentric cohort of 48 patients with an average
      age of 12 years was radiographically reviewed at 50 months. Cobb angle of
      fractured vertebra and regional Cobb angle were measured both at baseline and
      follow-up. Analyses were done according to initial Risser grade, number of
      fractures and level of injury. RESULTS: There was a total of 11 scoliosis. In
      group with Risser grade 3 or above, with a single vertebral fracture and lumbar
      fracture, final regional Cobb angle was statistically higher than initial
      regional Cobb angle. CONCLUSIONS: The prevalence of scoliosis in our population
      is higher than those of idiopathic scoliosis; Risser grade 3 or above, lumbar
      fracture and a single fracture seem to account for more severe coronal
      deformation.

PMID- 25572149
TI  - Annual changes in radiographic indices of the spine in cerebral palsy patients.
AB  - PURPOSE: We estimated the annual changes in radiographic indices of the spine in
      cerebral palsy (CP) patients and analyzed the factors that influence its
      progression rate. METHODS: We included CP patients who had undergone whole-spine
      radiography more than twice and were followed for at least 1 year. The scoliosis
      Cobb angle, coronal balance, apical vertebral translation, apical rotation, and
      pelvic obliquity were measured on anteroposterior (AP) radiographs; thoracic
      kyphosis and lumbar lordosis angles, and sagittal balance was measured on lateral
      radiographs; and migration percentage was measured on AP hip radiographs to
      determine hip instability. For each gross motor function classification system
      (GMFCS) level, the Cobb angles, apical vertebral translation, coronal and
      sagittal balance, and pelvic obliquity were adjusted by multiple factors with a
      linear mixed model. RESULTS: A total of 184 patients (774 radiographs) were
      included in this study. There was no significant annual change in scoliosis Cobb,
      thoracic kyphosis, and lumbar lordosis angles in the GMFCS level I-II and III
      groups. In the GMFCS level IV-V group, there was an annual increase of 3.4
      degrees  in the scoliosis Cobb angle (p = 0.020). The thoracic kyphosis angle
      increased by 2.2 degrees  (p = 0.018) annually in the GMFCS level IV-V group.
      Apical vertebral translation increased by 5.4 mm (p = 0.029) annually in the
      GMFCS level IV-V group. Progression of coronal and sagittal balance and pelvic
      obliquity with aging were not statistically significant. Sex, hip instability,
      hip surgery, and triradiate cartilage did not affect the progression of scoliosis
      and the balance of the spine and pelvis. CONCLUSIONS: The scoliosis Cobb angle,
      thoracic kyphosis angle, and apical vertebral translation in the GMFCS level IV-V
      CP patients progressed with age. These findings can predict radiographic
      progression of scoliosis in CP patients.

PMID- 25572150
TI  - Cross-cultural adaptation and validation of the Hungarian version of the Core
      Outcome Measures Index for the back (COMI Back).
AB  - PURPOSE: The Core Outcome Measure Index (COMI) is a short, multidimensional
      outcome instrument developed for the evaluation of patients with spinal
      conditions. The aim of this study was to produce a cross-culturally adapted and
      validated Hungarian version of the COMI Back questionnaire. METHODS: A cross
      cultural adaptation of the COMI into Hungarian was carried out using established
      guidelines. Low back pain patients completed a booklet of questionnaires
      containing the Hungarian versions of COMI, Oswestry Disability Index (ODI) and
      WHO Quality of Life-BREF assessment (WHOQOL-BREF). The validation of the COMI
      included assessment of its construct validity, reliability, and responsiveness.
      RESULTS: 145 patients participated in the assessment of reliability and 159
      surgically treated patients were included in the responsiveness study. Excellent
      correlation was found between COMI and ODI scores (rho = 0.83, p < 0.01). The
      COMI showed a very good correlation with the physical subscale of WHOQOL-BREF
      (rho = -0.75, p < 0.01) and pain (rho = 0.68, p < 0.01). Test-retest analysis
      showed that Hungarian COMI is a reliable measurement tool (ICC = 0.92) with an
      acceptable standard error of measurement (SEM = 0.59) and minimum detectable
      change (MDC = 1.63). Internal responsiveness analysis indicated a large effect
      size (1.16) for the change in COMI score after lumbar surgery. The area under the
      ROC curve (AUC) for the COMI score compared with the global outcome of the
      surgery was 0.87. CONCLUSION: The translation and cross-cultural adaptation of
      the COMI into the Hungarian language was successful, resulting in a reliable and
      valid measurement tool with good clinimetric properties.

PMID- 25572151
TI  - [Retrospective study about 73 consecutive patients treated by direct oral
      anticoagulant and admitted to an emergency room].
AB  - INTRODUCTION: Direct oral anticoagulants are a recent alternative to vitamin K
      antagonists but there is a lack of data regarding patients receiving these new
      types of treatment. The aim of the study was to identify and describe patients
      receiving direct oral anticoagulants admitted to an emergency unit. METHODS: All
      the patients taking direct oral anticoagulants, admitted to the emergency room of
      the Clermont-Ferrand Hospital from January to August 2013, were included in this
      retrospective and descriptive study. RESULTS: Among the 73 patients included,
      47.9% were treated with dabigatran and 52.1% with rivaroxaban. The indication was
      stroke prevention in 62 patients with atrial fibrillation whose average CHADS2
      score was 2.6 [2.3-3](IC95%). The average age was 76.4 years [73.7-79.1](IC95%).
      Twenty-nine patients (39.7%) had at least one drug association known for
      increasing the risk of bleeding. Average scores for bleeding risk were: HAS-BLED
      3.1 [2.9-3.3](IC95%) and Beyth 1.5 [1.3-1.6](IC95%). Bleeding patients included a
      higher percentage of men (68.8 vs. 38.2%, P=0.032). Creatinine clearance was
      lower in patients with major bleeding (45.2% vs. 68.8 mL/min, P=0.002). The Beyth
      score was highest in both sub-groups. CONCLUSION: In our study, we have found
      that the bleeding risk factors were: male gender, a high Beyth score, and a
      lowered creatinine clearance. Overall, patients treated with direct oral
      anticoagulants admitted to the emergency room were old with many co-morbidities,
      especially cardiovascular conditions; polymedication was frequent.

PMID- 25572152
TI  - [Pseudoaneurysm of the radial artery in the hand].
AB  - Over 1,400,000 cases of hand trauma are identified each year in France, with a
      large proportion with open wounds, accounting for significant activity in
      orthopedic surgery emergency units. It is customary to focus on nerve or tendon
      injuries as a priority. However, even partial vascular lesions may be complicated
      by a false aneurysm. We report the case of a false aneurysm of the palmar branch
      of the radial artery in 25-year-old man, 6 months after a non-treated puncture
      wound of the thenar eminence. Surgery was undertaken because of increased volume
      and discomfort on gripping. The surgical procedure consisted of resection and
      arterial ligature, after a positive preoperative Allen test. Hand aneurysms
      require an individualized therapeutic procedure. Origins may be diverse; the
      palmar digital location requires complex treatment. Compensation via a collateral
      arterial network is required for the vascular steal following ligation and
      resection. Careful exploration is needed to ensure appropriate compensation.
      Otherwise, a revascularization procedure must be considered. Some authors propose
      new less invasive treatments as an alternative to surgery. Even though surgery is
      relatively simple, the best means of prevention still remains a systematic
      exploration of vascular elements in case of a hand wound.

PMID- 25572153
TI  - Erectile dysfunction after sickle cell disease-associated recurrent ischemic
      priapism: profile and risk factors.
AB  - INTRODUCTION: Risk factors associated with erectile dysfunction (ED) that results
      from recurrent ischemic priapism (RIP) in sickle cell disease (SCD) are
      incompletely defined. AIM: This study aims to determine and compare ED risk
      factors associated with SCD and non-SCD-related "minor" RIP, defined as having
      >=2 episodes of ischemic priapism within the past 6 months, with the majority
      (>75%) of episodes lasting <5 hours. METHODS: We performed a retrospective study
      of RIP in SCD and non-SCD patients presenting from June 2004 to March 2014 using
      the International Index of Erectile Function (IIEF), IIEF-5, and priapism
      specific questionnaires. MAIN OUTCOME MEASURES: Prevalence rates and risk factor
      correlations for ED associated with RIP. RESULTS: The study was comprised of 59
      patients (40 SCD [mean age 28.2 +/- 8.9 years] and 19 non-SCD [15 idiopathic and
      four drug-related etiologies] [mean age 32.6 +/- 11.7 years]). Nineteen of 40
      (47.5%) SCD patients vs. four of 19 (21.1%) non-SCD patients (39% overall) had ED
      (IIEF <26 or IIEF-5 <22) (P = 0.052). SCD patients had a longer mean time-length
      with RIP than non-SCD patients (P = 0.004). Thirty of 40 (75%) SCD patients vs.
      10 of 19 (52.6%) non-SCD patients (P = 0.14) had "very minor" RIP (episodes
      regularly lasting <=2 hours). Twenty-eight of 40 (70%) SCD patients vs. 14 of 19
      (73.7%) non-SCD patients had weekly or more frequent episodes (P = 1). Of all
      patients with very minor RIP, ED was found among 14 of 30 (46.7%) SCD patients
      vs. none of 10 (0%) non-SCD patients (P = 0.008). Using logistic regression
      analysis, the odds ratio for developing ED was 4.7 for SCD patients, when
      controlling for RIP variables (95% confidence interval: 1.1-21.0). CONCLUSIONS:
      ED is associated with RIP, occurring in nearly 40% of affected individuals
      overall. SCD patients are more likely to experience ED in the setting of "very
      minor" RIP episodes and are five times more likely to develop ED compared with
      non-SCD patients.

PMID- 25572155
TI  - Low expression of miR-126 is a prognostic marker for metastatic clear cell renal
      cell carcinoma.
AB  - Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with unpredictable
      behavior. Clinical parameters are not always accurate for predicting prognosis.
      miR-126 is differentially expressed in many cancers, including RCC, and is down
      regulated in metastatic versus primary ccRCC. We assessed the prognostic
      significance of miR-126 in 264 primary ccRCCs. We also compared its expression in
      normal kidney, primary and metastatic ccRCC, and RCC subtypes. We validated our
      results on an independent set of 481 ccRCCs. miR-126 was down-regulated in
      metastatic versus primary tumors and in tumors of higher stage (P = 0.005) or
      higher grade (P = 0.002). miR-126 up-regulation was associated with significantly
      prolonged disease-free survival (P < 0.001) and overall survival (P = 0.015). For
      larger tumors (>4 cm), patients with higher miR-126 expression had significantly
      longer survival. Restoration of miR-126 expression decreased cellular migration
      and proliferation in RCC cell lines. The ccRCCs exhibited the highest miR-126
      expression, and papillary RCCs exhibited the lowest expression. We identified a
      number of miR-126 targets and pathways that are involved in carcinogenesis,
      including the apoptosis signaling pathway. miR-126 is a promising prognostic
      marker in ccRCC that can distinguish between clear cell and papillary subtypes.
      In addition, miR-126 has potential therapeutic applications. 

PMID- 25572154
TI  - Identification of a human papillomavirus-associated oncogenic miRNA panel in
      human oropharyngeal squamous cell carcinoma validated by bioinformatics analysis
      of the Cancer Genome Atlas.
AB  - High-risk human papillomavirus (HPV) is a causative agent for an increasing
      subset of oropharyngeal squamous cell carcinomas (OPSCCs), and current evidence
      supports these tumors as having identifiable risk factors and improved response
      to therapy. However, the biochemical and molecular alterations underlying the
      pathobiology of HPV-associated OPSCC (designated HPV(+) OPSCC) remain unclear.
      Herein, we profile miRNA expression patterns in HPV(+) OPSCC to provide a more
      detailed understanding of pathologic molecular events and to identify biomarkers
      that may have applicability for early diagnosis, improved staging, and prognostic
      stratification. Differentially expressed miRNAs were identified in RNA isolated
      from an initial clinical cohort of HPV(+/-) OPSCC tumors by quantitative PCR
      based miRNA profiling. This oncogenic miRNA panel was validated using miRNA
      sequencing and clinical data from The Cancer Genome Atlas and miRNA in situ
      hybridization. The HPV-associated oncogenic miRNA panel has potential utility in
      diagnosis and disease stratification and in mechanistic elucidation of molecular
      factors that contribute to OPSCC development, progression, and differential
      response to therapy. 

PMID- 25572156
TI  - Matrine inhibits the invasive properties of human glioma cells by regulating
      epithelial-to-mesenchymal transition.
AB  - Matrine is reported to be effective in tumor therapies; however, the anti
      metastatic effect and molecular mechanism(s) of matrine on glioma remain poorly
      understood. Therefore, the purpose of this study was to assess the effects of
      matrine on glioma and the associated mechanism(s). In the study, we demonstrated
      that matrine inhibited the proliferation of glioma cells. We also observed that
      matrine inhibited the migration and invasion of glioma cells at non-toxic
      concentrations. Matrine also decreased the expression of E-cadherin and increased
      the expression of N-cadherin. These results suggest that the anti-metastatic
      effect of matrine may be correlated with epithelial-to-mesenchymal transition
      (EMT). Moreover, matrine could reduce the phosphorylation levels of p38 and AKT
      proteins. In conclusion, these results suggest matrine may be a potential
      alternative against invasive glioma cells via the p38 MAPK and AKT signaling
      dependent inhibition of EMT.

PMID- 25572157
TI  - A novel equitation to predict the pressure derived collateral flow index in
      multiple sequential coronary stenoses.
AB  - Coronary collateral circulation is an alternative source of blood supply to the
      myocardium when the original blood flow is not sufficient. The pressure derived
      collateral flow index (CFI) calculated with (P w - P v)/(P a - P v) can be
      measured during angioplasty and predicts the outcome of the patients with
      ischemic heart disease. However, the necessity of occluding the coronary artery
      at maximum hyperemia hampers the wide spread use. We mathematically derived a new
      equation which calculates CFI in sequential stenoses. The present study aimed to
      validate the equation in an in vitro model of coronary circulation. The predicted
      CFI is calculated from the following equation: CFI = (FFRpre - FFRpost(1 -
      ?FFR))/(FFRpre + ?FFR - FFRpost). FFRpre/post is the FFR before and after the
      angioplasty. ?FFR is the FFR gradient across the target stenosis. The
      experimental system consisted of a pump, systemic circulation, coronary
      circulation, and 5 constrictors placed in the coronary artery. A total of 30
      different sequential coronary stenoses were randomly created and 30 different
      pressure data were obtained. The predicted CFI was compared with the true CFI. A
      close positive correlation (r = 0.90, p < 0.0001) was found between the predicted
      CFI and the true CFI. The accuracy of the equation was demonstrated in an in
      vitro model of coronary circulation. 

PMID- 25572159
TI  - Substantia nigra hyperechogenicity in hypokinetic Huntington's disease patients.
AB  - Substantia nigra (SN) hyperechogenicity can be detected by transcranial
      sonography (TCS) to assist the early diagnosis of idiopathic Parkinson's disease
      (IPD). This study prospectively investigated whether SN hyperechogenicity is also
      present in Huntington's disease (HD) patients with symptoms of hypokinesia and/or
      rigidity. All patients recruited to the study (n = 15) were characterised by
      hypokinesia and/or rigidity while nine of these patients also displayed chorea
      and/or dystonia. The control group included 15 individuals. Clinical examination
      was documented using the Unified Huntington's Disease Rating Scale (UHDRS). TCS
      examination revealed SN hyperechogenicity in 14/15 (93.3 %) patients (9/14
      unilateral, 5/14 bilateral). Hyperechogenicity of the caudate and lentiform
      nuclei (CN, LN) was less frequent (CN: 80 % total, LN: 53.3 % total). This is the
      first study to assess SN hyperechogenicity in hypokinetic HD patients. Assuming
      that the primary sites of pathology in IPD and HD are the SN and the striatum,
      respectively, our observations suggest a functional impairment of the
      nigrostriatal system in HD, an effect that is potentially independent of the
      primarily-affected basal ganglia nucleus.

PMID- 25572158
TI  - Sulfamethoxazole-trimethoprim associated with resveratrol for the treatment of
      toxoplasmosis in mice: Influence on the activity of enzymes involved in brain
      neurotransmission.
AB  - This study aimed to investigate the influence of sulfamethoxazole-trimethoprim
      (ST) associated with resveratrol on the enzymatic activities of
      acetylcholinesterase (AChE), adenylate kinase (AK), pyruvate kinase (PK), and
      creatine kinase (CK) in the brain of mice experimentally infected by Toxoplasma
      gondii. For that, 60 mice were divided into ten groups with 6 animals each:
      groups A to D composed by healthy mice and groups E to J consisting of animals
      infected by T. gondii (VEG strain). Animals started treatment 20 days post
      infection for 10 consecutive days with oral doses of 0.5 mg kg(-1) of ST (groups
      B and F), 100 mg kg(-1) of free resveratrol (groups C and G) and inclusion
      complex of resveratrol (nanoparticles containing resveratrol) (groups D and H),
      as well as with an association of both drugs (groups I and J). The results showed
      increased (P < 0.001) AChE activity on infected animals (groups E-J) when
      compared to not-infected (A) animals, and also uninfected animals treated with ST
      (group B) had increased AChE activity. AK activity decreased (P < 0.001) in the
      infected and untreated (group E), differently from the other groups that did not
      differ. PK activity did not differ between groups (P > 0.05). When comparing
      control groups (uninfected (A) and infected (E)), we verified a significant (P <
      0.001) increase in CK activity in the brain, and it is noteworthy that the
      animals treated with resveratrol associated with ST (group I and J) had similar
      CK activity to those animals from the group A. Treatment with the combination of
      ST and resveratrol was able to reduce (P < 0.05) the number of parasitic cysts in
      the brain, thus reduced inflammatory infiltrates in the liver, and prevented the
      occurrence of hepatocytes lesions due to toxoplasmosis in mice. Based on these
      results, it is possible to conclude that increased AChE and CK activities after
      T. gondii infection did not change with the treatment of ST-resveratrol
      association. In addition, decreased AK activity caused by T. gondii infection was
      normalized by ST-resveratrol treatment. T. gondii infection and treatment does
      not affect PK activity in brain.

PMID- 25572160
TI  - Right mesial temporal lobe epilepsy impairs empathy-related brain responses to
      dynamic fearful faces.
AB  - Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with reduced
      amygdala responsiveness to fearful faces. However, the effect of unilateral MTLE
      on empathy-related brain responses in extra-amygdalar regions has not been
      investigated. Using functional magnetic resonance imaging, we measured empathy
      related brain responses to dynamic fearful faces in 34 patients with unilateral
      MTLE (18 right sided), in an epilepsy (extra-MTLE; n = 16) and in a healthy
      control group (n = 30). The primary finding was that right MTLE (RMTLE) was
      associated with decreased activity predominantly in the right amygdala and also
      in bilateral periaqueductal gray (PAG) but normal activity in the right anterior
      insula. The results of the extra-MTLE group demonstrate that these reduced
      amygdala and PAG responses go beyond the attenuation caused by antiepileptic and
      antidepressant medication. These findings clearly indicate that RMTLE affects the
      function of mesial temporal and midbrain structures that mediate basic
      interoceptive input necessary for the emotional awareness of empathic experiences
      of fear. Together with the decreased empathic concern found in the RMTLE group,
      this study provides neurobehavioral evidence that patients with RMTLE are at
      increased risk for reduced empathy towards others' internal states and sheds new
      light on the nature of social-cognitive impairments frequently accompanying MTLE.

PMID- 25572163
TI  - Novel ATM mutation in a German patient presenting as generalized dystonia without
      classical signs of ataxia-telangiectasia.

PMID- 25572162
TI  - Patient outcome in the Belgian medical need program on bevacizumab for recurrent
      glioblastoma.
AB  - Bevacizumab (BEV) has demonstrated anti-tumor activity in patients with recurrent
      glioblastoma (rGB). Given the unmet need for active therapeutic options in rGB
      patients, a medical need program was initiated by the Belgian competent
      authorities. Between November 2010 and February 2013, a total of 313 patients
      with rGB initiated treatment with BEV administered at a dose of 10 mg/kg every 2
      weeks. All patients had failed prior treatment with at least radiation therapy
      and temozolomide and the majority of patients (70 %) were treated with
      corticosteroids at baseline. Patients received a median of 6 BEV administrations
      (range 1-53). Overall, BEV was well tolerated. During BEV treatment the WHO
      Performance Score (WHO-PS) improved in 59 patients (19 %) and stabilized for at
      least 6 weeks in an additional 139 (44 %) patients. Corticosteroid treatment
      could be stopped in 16 % or reduced in dose in 32 % of patients. The best
      objective tumor response rate using RANO criteria (investigator's assessment) was
      3.5 % CR, 22 % PR, 38 % SD and 37 % PD. The median and 6-month PFS were 13 weeks
      (95 % CI 12.7-14) and 27.3 % (95 % CI 22.3-32.5), median and 6-month OS rates
      were 26 weeks (23-29) and 52 % (46.4-58.6), respectively. WHO-PS (0-1 vs. 2-3)
      and baseline steroid use were significantly correlated with PFS and OS. Our
      observations support the use of BEV as a monotherapy for patients with rGB who
      have no alternative treatment options. Optimal benefit from BEV treatment is
      likely to be obtained when treatment is initiated before the performance status
      deteriorates to two or less.

PMID- 25572161
TI  - Morphometric and functional MRI changes in essential tremor with and without
      resting tremor.
AB  - The etiopathogenesis of essential tremor (ET) is still debated, since the
      predominant role of circuit dysfunction or brain degenerative changes has not
      been clearly established. The relationship with Parkinson's Disease (PD) is also
      controversial and resting tremor occurs in up to 20 % of ET. We investigated the
      morphological and functional changes associated with ET and we assessed potential
      differences related to the presence (ET+R) or absence (ET-R) of resting tremor.
      32 ET patients (18 ET+R; 14 ET-R) and 12 healthy controls (HC) underwent 3T-MRI
      protocol including Spoiled Gradient T1-weighted sequence for Voxel-Based
      Morphometry (VBM) analysis and functional MRI during continuous writing of "8"
      with right dominant hand. VBM analysis revealed no gray and white matter atrophy
      comparing ET patients to HC and ET+R to ET-R patients. HC showed a higher BOLD
      response with respect to ET patients in cerebellum and other brain areas
      pertaining to cerebello-thalamo-cortical circuit. Between-group activation maps
      showed higher activation in precentral gyrus bilaterally, right superior and
      inferior frontal gyri, left postcentral gyrus, superior and inferior parietal
      gyri, mid temporal and supramarginal gyri, cerebellum and internal globus
      pallidus in ET-R compared to ET+R patients. Our findings support that the
      dysfunction of cerebello-thalamo-cortical network is associated with ET in
      absence of any morphometric changes. The dysfunction of GPi in ET+R patients,
      consistently with data reported in PD resting tremor, might suggest a potential
      role of this structure in this type of tremor. 

PMID- 25572164
TI  - Expression of ST3Gal, ST6Gal, ST6GalNAc and ST8Sia in human hepatic carcinoma
      cell lines, HepG-2 and SMMC-7721 and normal hepatic cell line, L-02.
AB  - We measured ST3Gal, ST6Gal, ST6GalNAc and ST8Sia expression in human hepatic
      carcinoma cell lines, HepG-2 and SMMC-7721 and normal hepatic cell line, L-02 to
      reveal the relationship between hepatic carcinoma cell lines sialyltransferases
      expression and cell membrane sialic acid sugar chains. Membrane sialic acid sugar
      chains in L-02, HepG-2 and SMMC-7721 cell lines were measured with lectin
      microarrays to find expression profiles. Expression of 20 sialyltransferases was
      measured with DNA microarray. qRT-PCR and Western blot were used to verify DNA
      microarrays data. Siaalpha 2-3Galbeta1-3[Siaalpha2-6GalNAc]alpha-R and Siaalpha 2
      6Gal/GalNAc sugar chains in hepatic carcinoma cell lines, HepG-2 and SMMC-7721
      were upregulated, and 7differentially expressed sialyltransferases were captured.
      ST3Gal-IV and ST6Gal I were overexpressed and ST3Gal-I, ST3Gal-V, ST3Gal-VI,
      ST6GalNAcII and ST6GalNAcVI were downregulated in HepG-2 and SMMC-7721 cell
      Lines, compared with control cell line. ST6GalNAc-IV and ST8sia expressions were
      not detected. Other sialyltransferases were not different among cell lines.
      Results from qRT-PCR and Western blot were consistent with DNA microarray.
      Overexpression of ST3Gal-IV and ST6Gal I in HepG-2 and SMMC-7721 cell lines may
      correlate with upregulation of Siaalpha 2-3Galbeta1-3[Siaalpha2-6GalNAc]alpha-R
      and Siaalpha 2-6Gal/GalNAc sugar chains on cell membranes. 

PMID- 25572165
TI  - Toxin effect on protein biosynthesis in eukaryotic cells: a simple kinetic model.
AB  - A model for toxin inhibition of protein synthesis inside eukaryotic cells is
      presented. Mitigation of this effect by introduction of an antibody is also
      studied. Antibody and toxin (ricin) initially are delivered outside the cell. The
      model describes toxin internalization from the extracellular into the
      intracellular domain, its transport to the endoplasmic reticulum (ER) and the
      cleavage inside the ER into the RTA and RTB chains, the release of RTA into the
      cytosol, inactivation (depurination) of ribosomes, and the effect on translation.
      The model consists of a set of ODEs which are solved numerically. Numerical
      results are illustrated by figures and discussed. 

PMID- 25572167
TI  - Parental age and attenuated thought disorder in a cohort at clinical high risk
      for psychosis.

PMID- 25572166
TI  - Monsplasty after massive weight loss: Assessment of its aesthetic and functional
      impact.
AB  - INTRODUCTION: Massive weight loss frequently leads to a ptosis or a pubic bulge.
      This deformation is a source of functional as well as aesthetic discomfort, and
      it also has psychological repercussions. We have analyzed the degree of
      satisfaction reported by 23 female patients having undergone a monsplasty
      procedure and have also proposed a decisional algorithm designed to facilitate
      surgical care according to type of pubic deformation. MATERIALS AND METHODS: This
      is a one-year prospective study involving 23 female patients having undergone a
      monsplasty procedure following massive weight loss. The interventions were all
      carried out in standardized fashion by the same surgeon according to stage of
      deformation. Analysis of the patients' degree of aesthetic and functional
      satisfaction was performed using a questionnaire filled out during preoperative
      and postoperative consultations, the latter taking place 6 months to one year
      after the operation. It included a self-esteem assessment based on the Rosenberg
      scale, appraisal of functional benefits (clothing, sexual activity, daily
      physical activities, intimate hygiene) and evaluation of the pubis in aesthetic
      terms. RESULTS: Assessment of impact on self-esteem revealed average improvement
      of 10.08 points, rising from 25.87 to 35.95. All of the patients, without
      exception, were satisfied or very satisfied with the impact of monsplasty on the
      different items under evaluation. stage 3 and stage 4 patients were particularly
      sensitive to improvement involving personal hygiene, physical activities and the
      clothes they wore. In most cases, they likewise reported a positive impact on
      their sexual experience. CONCLUSION: Abdominoplasty or body lift without
      monsplasty can entail long-lasting aesthetic and functional discomfort. Thorough
      preoperative semiological analysis is essential to optimized surgical care
      conducive to successful integration of the monsplasty. An appropriate caretaking
      attitude enhances both the aesthetic result and patient self-esteem.

PMID- 25572168
TI  - Mucosal relapse of visceral leishmaniasis in a child treated with anti-TNFalpha.
AB  - Visceral leishmaniasis is an enzootic parasitosis present across the
      Mediterranean Basin. Some consider it an opportunistic parasite. We report the
      case of a girl treated with anti-tumour necrosis factor alpha (anti-TNFalpha) for
      juvenile idiopathic arthritis who had previously presented with visceral
      leishmaniasis. Two and a half years later, she presented a tumour-like mass in
      the nasal mucous membrane caused by Leishmania parasites. Leishmania infantum is
      classically responsible for visceral leishmaniasis, but pure mucocutaneous
      leishmaniasis has also been described. To our knowledge, this is the first
      observation of a recurrence of visceral leishmaniasis in the mucocutaneous form.
      The occurrence of atypical forms and presentations in those on anti-TNF therapy
      should be considered. 

PMID- 25572169
TI  - IgM MGUS associated with anti-MAG neuropathy: a single institution experience.
AB  - Anti-MAG neuropathy is a very rare form of acquired polyneuropathy associated
      with IgM monoclonal gammopathy of undetermined significance (MGUS). We conducted
      a retrospective review of 194 consecutive MGUS patients seen at the Penn State
      Hershey Cancer Institute. We identified six patients among 37 (16 %) with IgM
      MGUS with anti-MAG neuropathy. Interestingly, an additional patient had anti-MAG
      neuropathy without MGUS. Common clinical manifestations were numbness and
      paresthesias of the extremities and gait imbalance. All four patients treated
      with rituximab and none of the three untreated ones had a subjective improvement
      of their symptoms. We conclude that all patients with IgM MGUS and neuropathy
      should be screened for anti-MAG antibodies and, if positive, they should be
      offered treatment with rituximab. 

PMID- 25572170
TI  - Prognostic significance of diagnosed WT1 level in acute myeloid leukemia: a meta
      analysis.
AB  - The Wilms' tumor 1 (WT1) expression has been recognized in a substantial number
      of acute myeloid leukemia (AML) patients. Some studies indicated the association
      of diagnosed WT1 higher expression (WT1(H)) and poor outcome in the AML patients,
      while other studies had different opinions. Therefore, we performed a meta
      analysis to evaluate the controversial prognostic significance of diagnosed
      WT1(H) in AML. Eligible studies were identified from several databases including
      PubMed, Embase, Web of Science, and the Cochrane Library (up to September 2014).
      The primary end point was overall survival (OS) and disease-free survival (DFS)
      was chosen as secondary end point. If possible, we would pool estimate effects
      (hazard ratio [HR] with 95 % confidence interval [CI]) of outcomes in both fixed
      and random effects models. Eleven studies, covering 1497 AML patients, were
      included in this meta-analysis. Pooled HRs indicated that diagnosed WT1(H) had a
      poor impact on the survival of AML patients (HR for OS, 1.37; HR for DFS, 1.38).
      Furthermore, diagnosed WT1(H) appeared to be an adverse prognostic indicator in
      adult AML (HR for OS, 1.43; HR for DFS, 1.41) and non-promyelocytic AML (non-M3
      AML) (HR for OS, 1.46; HR for DFS, 1.41). Diagnosed WT1(H) had slightly but
      significantly poor prognostic impact on OS and DFS of patients with AML in total
      population and some specific subgroups. 

PMID- 25572171
TI  - Cytomegalovirus retinitis complicating combination therapy with rituximab and
      fludarabine.
AB  - Cytomegalovirus (CMV) retinitis is exceptionally rare outside the clinical
      context of acquired immunodeficiency syndrome and organ allografting. In a
      population where seropositivity for past CMV infection exceeded 90 %, CMV
      retinitis was observed in five of 138 patients (3.6 %) receiving fludarabine
      containing regimens together with rituximab, which was significantly more
      frequent than in 141 patients receiving fludarabine-containing regimens alone,
      where no case was observed (P = 0.029). Treatment of CMV retinitis comprised both
      intravitreal and systemic ganciclovir/foscarnet. Upon recovery, secondary retinal
      atrophy occurred in all patients, leading to blindness in 86 % of affected eyes.
      CMV retinitis is an important complication in patients receiving concomitant
      rituximab and fludarabine-containing regimens. 

PMID- 25572175
TI  - Metabolic syndrome risk factors are associated with white rice intake in Korean
      adolescent girls and boys.
AB  - In the present study, we examined the associations of total carbohydrate intake,
      dietary glycaemic load (DGL) and white rice intake with metabolic syndrome risk
      factors by sex in Korean adolescents. For the present cross-sectional study, data
      from the Fourth Korea National Health and Nutrition Examination Survey (2007-9)
      were used. A total of 2209 adolescents (n 1164 boys and n 1045 girls) aged 10-18
      years with complete anthropometric, biochemical and dietary intake data were
      included in the study. Dietary intake data were obtained using the 24 h recall
      method, and total carbohydrate intake, DGL and white rice intake were divided
      into quartiles by sex. The metabolic syndrome and its risk factors were defined
      using the International Diabetes Federation criteria for children and
      adolescents. Fasting insulin levels and insulin resistance were included as the
      metabolic syndrome risk factors. All statistical analyses considered the complex
      sampling design effect and appropriate sampling weights. Multivariate linear
      regression analysis was used to estimate means with their standard errors of the
      mean for the metabolic syndrome risk factors across the quartiles of total
      carbohydrate intake, DGL and white rice intake. While high DGL was significantly
      associated with increased fasting glucose levels in boys, high total carbohydrate
      intake, DGL and white rice intake were consistently associated with reduced HDL
      cholesterol levels in girls. High white rice intake was significantly associated
      with an increased risk of insulin resistance and the metabolic syndrome in girls
      but not in boys. Optimising dietary carbohydrate intake with respect to the
      source or amount is fundamental to preventing and managing metabolic diseases in
      Asian adolescents. 

PMID- 25572176
TI  - Brainstem auditory response findings in very preterm babies in the intensive care
      unit.
AB  - BACKGROUND: There is a need to increase our understanding of whether there is
      compromised brainstem auditory function in very preterm babies in intensive care.
      OBJECTIVES: To evaluate brainstem auditory function in preterm babies born at 32
      weeks of gestation or earlier in the intensive care unit to detect any
      abnormality and the prevalence of the abnormality. METHODS: We analyzed the
      brainstem auditory evoked response (BAER) at term in 156 babies born at 32 weeks
      of gestation or earlier in an intensive care unit. The data were compared to
      those of normal term babies to detect any differences. RESULTS: The threshold of
      BAER was elevated in babies born at 32 weeks of gestation or earlier. All BAER
      wave latencies were significantly increased. The I-V interpeak interval was also
      increased. The amplitudes of BAER components tended to be reduced. Twenty-five
      (16.0%) babies in the intensive care unit had a BAER threshold elevation (>20 dB
      normal hearing level), suggesting peripheral auditory dysfunction. Thirty-three
      (21.1%) had an increased I-V interval, and 3 (1.9%) had a decreased V/I amplitude
      ratio, suggesting central or brainstem auditory dysfunction. Some babies had more
      than one BAER abnormality. As a whole, 51 (32.7%) babies had BAER abnormalities.
      CONCLUSION: Very preterm babies in the intensive care unit are at a high risk for
      auditory dysfunction. At term, 1 in 3 of these babies has peripheral and/or
      central auditory dysfunction.

PMID- 25572172
TI  - JAK-STAT pathway activation in malignant and nonmalignant cells contributes to
      MPN pathogenesis and therapeutic response.
AB  - The identification of JAK2/MPL mutations in patients with myeloproliferative
      neoplasms (MPN) has led to the clinical development of JAK kinase inhibitors,
      including ruxolitinib. Ruxolitinib reduces splenomegaly and systemic symptoms in
      myelofibrosis and improves overall survival; however, the mechanism by which JAK
      inhibitors achieve efficacy has not been delineated. Patients with MPN present
      with increased levels of circulating proinflammatory cytokines, which are
      mitigated by JAK inhibitor therapy. We sought to elucidate mechanisms by which
      JAK inhibitors attenuate cytokine-mediated pathophysiology. Single-cell profiling
      demonstrated that hematopoietic cells from myelofibrosis models and patient
      samples aberrantly secrete inflammatory cytokines. Pan-hematopoietic Stat3
      deletion reduced disease severity and attenuated cytokine secretion, with similar
      efficacy as observed with ruxolitinib therapy. In contrast, Stat3 deletion
      restricted to MPN cells did not reduce disease severity or cytokine production.
      Consistent with these observations, we found that malignant and nonmalignant
      cells aberrantly secrete cytokines and JAK inhibition reduces cytokine production
      from both populations. SIGNIFICANCE: Our results demonstrate that JAK-STAT3
      mediated cytokine production from malignant and nonmalignant cells contributes to
      MPN pathogenesis and that JAK inhibition in both populations is required for
      therapeutic efficacy. These findings provide novel insight into the mechanisms by
      which JAK kinase inhibition achieves therapeutic efficacy in MPNs.

PMID- 25572173
TI  - Combined inhibition of MAP kinase and KIT signaling synergistically destabilizes
      ETV1 and suppresses GIST tumor growth.
AB  - Gastrointestinal stromal tumor (GIST), originating from the interstitial cells of
      Cajal (ICC), is characterized by frequent activating mutations of the KIT
      receptor tyrosine kinase. Despite the clinical success of imatinib, which targets
      KIT, most patients with advanced GIST develop resistance and eventually die of
      the disease. The ETS family transcription factor ETV1 is a master regulator of
      the ICC lineage. Using mouse models of Kit activation and Etv1 ablation, we
      demonstrate that ETV1 is required for GIST initiation and proliferation in vivo,
      validating it as a therapeutic target. We further uncover a positive feedback
      circuit where MAP kinase activation downstream of KIT stabilizes the ETV1
      protein, and ETV1 positively regulates KIT expression. Combined targeting of ETV1
      stability by imatinib and MEK162 resulted in increased growth suppression in
      vitro and complete tumor regression in vivo. The combination strategy to target
      ETV1 may provide an effective therapeutic strategy in GIST clinical management.
      SIGNIFICANCE: ETV1 is a lineage-specific oncogenic transcription factor required
      for the growth and survival of GIST. We describe a novel strategy of targeting
      ETV1 protein stability by the combination of MEK and KIT inhibitors that
      synergistically suppress tumor growth. This strategy has the potential to change
      first-line therapy in GIST clinical management.

PMID- 25572177
TI  - The Impact of Patient Suicide on the Professional Practice of Swiss Psychiatrists
      and Psychologists.
AB  - OBJECTIVES: Many psychiatrists and psychologists are likely to experience a
      patient suicide at a point in their professional career. The present paper
      examines the effects of patient suicide on psychiatrists' and psychologists'
      professional reactions and working practices and investigates factors that may
      affect the severity of repercussions on their professional lives. METHOD: Data
      from 271 psychiatrists and psychologists working in various institutional
      settings and in private practice in French-speaking Switzerland were collected by
      a written questionnaire. RESULTS: Psychiatrists and psychologists reported a
      range of professional reactions and changes in working practices following a
      patient suicide. Professional reactions and changes in working practices were
      more significant among women. The length of therapy and the emotional closeness
      with the deceased patient were predictive of a greater impact. In contrast,
      social and psychological support served as a protective factor by reducing
      negative repercussions on professional practice. Finally, the impact of losing a
      patient to suicide did not differ between psychiatrists and psychologists in
      institutional settings and those in private practice. CONCLUSION: Although
      patient suicide affected the professional life of psychiatrists and
      psychologists, it also encouraged them to review and adjust their working
      practices.

PMID- 25572179
TI  - Editors made and born.

PMID- 25572178
TI  - The program director scholar: aspiration and perspiration.

PMID- 25572180
TI  - Rs1800625 in the receptor for advanced glycation end products gene predisposes to
      sepsis and multiple organ dysfunction syndrome in patients with major trauma.
AB  - INTRODUCTION: The receptor for advanced glycation end products (RAGE) is a
      transmembrane receptor of the immunoglobulin superfamily, it plays pivotal roles
      in the pathogenesis of sepsis in several ways. Our previous study showed that
      rs1800625 (-429T/C) revealed a strong clinical relevance with sepsis morbidity
      rate and multiple organ dysfunction syndrome (MODS) in patients with major
      trauma. In this study, we enlarged the sample size, added two validation
      populations and examined the expression of RAGE on the surface of peripheral
      leukocytes to ex vivo lipopolysaccharide (LPS) stimulation in subjects with
      different genotypes. METHODS: Rs1800625 was genotyped using pyrosequencing in 837
      Chinese Han patients with major trauma in Chongqing. We then validated the
      clinical relevance in 340 Zhejiang and 347 Yunnan patients. The expression of
      RAGE on the surface of peripheral blood mononuclear cells was measured by flow
      cytometric analysis. RESULTS: The results indicated that rs1800625 was
      significantly associated with sepsis morbidity rate and MODS in patients with
      major trauma in the Chongqing, Zhejiang and Yunnan districts. Patients with CC
      genotype had lower sepsis morbidity rate and MODS after major trauma.
      Furthermore, patients with CC genotype had significantly higher RAGE expression
      (P = 0.009). CONCLUSIONS: The rs1800625 polymorphism is a functional single
      nucleotide polymorphism and confers host susceptibility to sepsis and MODS in
      patients with major trauma.

PMID- 25572182
TI  - The first report of a homozygous codons 9/10 (+T) beta-thalassemia mutation in a
      Turkish patient.
AB  - For the first time in Turkey, we report a thalassemic patient with a homozygous
      codons 9/10 (+T) genotype. Currently, the patient is 3 years and 2 months old and
      received an initial transfusion at the age of 18 months. After being
      alloimmunized following this transfusion, he required frequent transfusions,
      every week to every other week. Although alloimmunization was controlled after
      methyl-prednisolone, intravenous immunoglobulin, plasmapheresis and rituximab,
      the transfusion requirements continued related to hypersplenism. Subsequent to
      splenectomy, transfusion requirements disappeared with average hemoglobin (Hb)
      levels around 11.0 g/dL. The mother underwent prenatal diagnosis (PND) when she
      became pregnant for the third time; this revealed a heterozygous codons 9/10
      fetus.

PMID- 25572181
TI  - One-year treatment with liraglutide improved renal function in patients with type
      2 diabetes: a pilot prospective study.
AB  - Unlike GLP-1, liraglutide is not cleared by the glomerulus and its
      pharmacokinetic is not altered in patients with mild renal impairment. The aim of
      our study was to analyze the effects of liraglutide on renal function in patients
      with type 2 diabetes. A twelve-month longitudinal prospective post-marketing
      study was performed. According to eGFR (estimated glomerular filtration rate)
      calculated with CKD-EPI equation, 84 consecutive patients were divided in Group A
      (eGFR > 90 ml/min) and Group B (eGFR < 90 ml/min). BMI, glucose, HbA1c, serum
      creatinine, microalbuminuria, and eGFR were evaluated at baseline and after 12
      months of treatment. A reduction in fasting plasma glucose (p < 0.01), HbA1c (p <
      0.003), BMI (p < 0.01), and systolic (p < 0.01) and diastolic blood pressure (p <
      0.006) was recorded irrespective of eGFR category. Concerning renal function,
      creatinine levels had a trend to decrease in both groups. eGFR did not change in
      Group A, while it increased in Group B (p < 0.05) independently from the
      concomitant changes of other parameters. Moreover, seven out of 41 patients of
      Group B had increased eGFR levels which reached the normal values (>90 ml/min).
      At baseline, five patients had pathological microalbuminuria, but at 12 months
      three of them returned to normal albuminuria (p < 0.006). Total microalbuminuria
      levels improved in both groups (p < 0.02). According to preliminary data in
      animals, our study shows that liraglutide is effective in preserving eGFR in
      diabetic patients, increasing it in those with reduced renal function. This was
      associated with a decrease of frequency of patients positive to microalbuminuria.
      Further studies are needed to confirm these data.

PMID- 25572183
TI  - Insulin resistance and beta cell function in patients with beta-thalassemia
      major.
AB  - Iron overload is a common finding in chronically transfused beta-thalassemia
      major (beta-TM) patients with possible effect on beta cell function and insulin
      resistance. In this study we aimed to evaluate glucose metabolism, insulin
      resistance and beta cell function in beta-TM patients. A total of 78 transfusion
      dependent beta-TM patients and 40 age and sex matched normal children were
      included. Oral glucose tolerance tests (OGTT) were performed in all subjects.
      Fasting plasma insulin level, insulin resistance index (IRI) and beta cell
      function index (BFI) were also estimated. beta-Thalassemia major patients had
      significantly more abnormal OGTT than the control group. beta-Thalassemia major
      patients had significantly higher levels of aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) fasting blood sugar and IRI than the control
      group. Findings between beta-thalassemia (beta-thal) patients, with and without
      abnormal OGTT results, were also compared; beta-thal patients with abnormal OGTT
      had significantly higher duration of chelation therapy, serum ferritin levels,
      AST, ALT and increased IRI and decreased BFI in comparison to patients with
      normal OGTT. Abnormal glucose metabolism is common in beta-TM patients with
      chelation therapy and multiple transfusions which are attributable to impaired
      beta cells' function and increased insulin resistance.

PMID- 25572184
TI  - Hb Feilding [beta12(A9)Thr -> Pro; HBB: c.37A>C]: a novel unstable beta-globin
      chain variant.
AB  - We report here a patient heterozygous for a previously unreported beta chain
      variant. A 72-year-old Caucasian female was found to have an abnormal hemoglobin
      (Hb) as an incidental finding following Hb A1C analysis. There was no family
      history of anemia or hemoglobinopathy. Her full blood count revealed a mild
      normochromic anemia with Hb 11.1 g/dL (range 11.5-15.0), mean corpuscular volume
      (MCV) 93.0 fL (range 80.0-100.0) and mean corpuscular Hb (MCH) 30.0 pg (range
      27.0-32.0). Isopropanol stability tests and a variant Hb on high performance
      liquid chromatography (HPLC) comprizing 37.0% of the total Hb suggested an
      unstable Hb variant. Sanger sequencing of the beta-globin gene revealed a single
      base substitution, HBB: c.37A>C, causing the missense mutation beta12(A9)Thr ->
      Pro in exon 1 of the HBB gene. This mutation changes the threonine residue at
      position 12(A9) to a proline in the beta-globin chain. We propose that this
      variant be called Hb Feilding after the town where the proband lived. Three
      dimensional modeling suggested that the disruption of the Hb structure was due to
      the introduction of a proline at helix A9 which caused distortion of the helical
      structure and resulted in reduced solubility.

PMID- 25572185
TI  - Cardiomyopathy associated with iron overload: how does iron enter myocytes and
      what are the implications for pharmacological therapy?
AB  - Iron overload cardiomyopathy is one of the most common causes of death in
      thalassemia patients. Although new iron chelating agents have been developed, the
      mortality rate from heart failure remains elevated as a result of iron overload.
      This could be due to the fact that our understanding of the underlying mechanism
      of iron uptake into cardiomyocytes is still unclear, thus impeding the discovery
      and refinement of more effective therapy for thalassemia therapeutic strategies
      in thalassemic iron overload cardiomyopathy. Growing evidence indicates that
      multiple routes of iron entry into cardiomyocytes exist under iron overload
      conditions. These include both L-type (LTCC) and T-type (TTCC) calcium channels,
      divalent metal transporter 1 (DMT1) and transferrin receptors (TfRs). In this
      review, the routes of iron uptake into cardiomyocytes under iron overload
      conditions are presented. Evidence from pharmacological interventions in support
      or against the possible route of iron entry of each portal in cardiomyocytes are
      also comprehensively summarized and discussed.

PMID- 25572186
TI  - Identification of a novel mutation in the beta-globin gene 3' untranslated region
      (HBB: c.*+118A > G) in Spain.
AB  - The 3' untranslated region (3'UTR) region is well known to be associated with
      mRNA stability because of its associations with 3' end processing,
      polyadenylation and mRNA capping. Mutations located in this area cause a beta
      thalassemia (beta-thal) phenotype compatible with beta(+)-thal. Two brothers, 49-
      and 41-years-old, were diagnosed with beta-thal intermedia (beta-TI) at 2 years
      of age. The beta-globin gene from the promoter region to the 3'UTR was sequenced
      and both brothers were diagnosed to be compound heterozygotes for the 3'UTR +1592
      (A > G) (HBB: c.*+118A > G) and codon 39 (C > T) (HBB: c.118C > T) mutations.
      Their mother was a carrier of the nonsense codon 39 mutation and her
      hematological data suggested beta-thal trait; their father was a carrier of the
      3'UTR +1592 mutation, though he did not have hematological parameters associated
      with beta-thal. The adenine at position +1592 or +118 bases downstream of the
      termination codon is highly conserved among primates and placental mammals, as it
      is located between the polyadenylation A signal (PAS) and the polyadenylation A
      cleavage (PAC) sites. Given its location, it is likely that this mutation would
      interfere with mRNA maturation; however, the clinical data of the heterozygous
      carriers show virtually no significant alterations. Therefore, we suggest that
      the impact on cleavage-stimulation factor (CstF) recognition of the mRNA sequence
      would be minimal and not significantly alter polyadenylation. Although the
      mechanism is not known, and because the carrier has no beta-thal minor, the mRNA
      is stable enough that the synthesis of the beta-globin chain is unaffected.

PMID- 25572187
TI  - Rare hemoglobin variants: Hb G-Szuhu (HBB: c.243C>G), Hb G-Coushatta (HBB:
      c.68A>C) and Hb Mizuho (HBB: c.206T>C) in Sri Lankan families.
AB  - In this short communication, we describe the clinical presentation of unusual
      hemoglobin (Hb), variants in three Sri Lankan cases under study for beta
      thalassemia intermedia (beta-TI). We believe this is the first report on their
      occurrence in Sri Lanka as well as from the Indian subcontinent. During a
      molecular study performed on beta-TI patients, we identified three unusual Hb
      variants as Hb G-Szuhu (HBB: c.243C>G), Hb G-Coushatta (HBB: c.68A>C) and Hb
      Mizuho (HBB: c.206T>C) in three unrelated families. Hb G-Szuhu and Hb G-Coushatta
      were found in combination with the common beta-thalassemia (beta-thal) mutation,
      IVS-I-5 (G>C). Both probands had mild anemia with greatly reduced red cell
      indices and had non palpable livers and spleens, however, by ultrasound, both
      were observed to be enlarged. The final Hb variant, Hb Mizuho, was identified as
      a heterozygous mutation found in both proband and his mother. Both family members
      had severe anemia and were regularly transfused and had increased red cell
      parameters.

PMID- 25572188
TI  - Evaluation of toxicity equivalent factors of paralytic shellfish poisoning toxins
      in seven human sodium channels types by an automated high throughput
      electrophysiology system.
AB  - Although voltage-gated sodium channels (Na v ) are the cellular target of
      paralytic shellfish poisoning (PSP) toxins and that patch clamp electrophysiology
      is the most effective way of studying direct interaction of molecules with these
      channels, nowadays, this technique is still reduced to more specific analysis due
      to the difficulties of transforming it in a reliable throughput system. Actual
      functional methods for PSP detection are based in binding assays using receptors
      but not functional Na v channels. Currently, the availability of automated patch
      clamp platforms and also of stably transfected cell lines with human Na v
      channels allow us to introduce this specific and selective method for fast
      screenings in marine toxin detection. Taking advantage of the accessibility to
      pure PSP standards, we calculated the toxicity equivalent factors (TEFs) for nine
      PSP analogs obtaining reliable TEFs in human targets to fulfill the deficiencies
      of the official analytic methods and to verify automated patch clamp technology
      as a fast and reliable screening method for marine toxins that interact with the
      sodium channel. The main observation of this work was the large variation of TEFs
      depending on the channel subtype selected, being remarkable the variation of
      potency in the 1.7 channel subtype and the suitability of Na v 1.6 and 1.2
      channels for PSP screening. 

PMID- 25572189
TI  - E-cigarettes: an asset or liability in efforts to lessen tobacco smoking and its
      consequences.

PMID- 25572190
TI  - Introduction to the Symposium on Pain Medicine.

PMID- 25572192
TI  - The safety of intravenous iron preparations: systematic review and meta-analysis.
AB  - OBJECTIVE: To amass all available evidence regarding the safety of intravenous
      (IV) iron preparations to provide a true balance of efficacy and safety. METHODS:
      Systematic review and meta-analysis of all randomized clinical trials comparing
      IV iron to another comparator. All electronic databases until January 1, 2014,
      were reviewed. Primary outcome was occurrence of severe adverse events (SAEs).
      Secondary outcomes included all-cause mortality and other adverse events (AEs).
      Subgroup analysis was performed on the basis of type of IV iron, comparator,
      treated condition, and system involved. RESULTS: A total of 103 trials published
      between 1965 through 2013 were included. A total of 10,390 patients were treated
      with IV iron compared with 4044 patients treated with oral iron, 1329 with no
      iron, 3335 with placebo, and 155 with intramuscular iron. There was no increased
      risk of SAEs with IV iron (relative risk [RR], 1.04; 95% CI, 0.93-1.17; I(2)=9%).
      Subgroup analysis revealed a decreased rate of SAEs when IV iron was used to
      treat heart failure (RR, 0.45; 95% CI, 0.29-0.70; I(2)=0%). Severe infusion
      reactions were more common with IV iron (RR, 2.47; 95% CI, 1.43-4.28; I(2)=0%).
      There was no increased risk of infections with IV iron. Gastrointestinal AEs were
      reduced with IV iron. CONCLUSION: Intravenous iron therapy is not associated with
      an increased risk of SAEs or infections. Infusion reactions are more pronounced
      with IV iron.

PMID- 25572194
TI  - Increased risk of osteoporosis in patients with depression: a population-based
      retrospective cohort study.
AB  - OBJECTIVE: To investigate the relationship between depression and risk of
      subsequent osteoporosis development. PARTICIPANTS AND METHODS: A population-based
      retrospective cohort analysis was conducted using the Longitudinal Health
      Insurance Database 2000 of Taiwan. We included 32,978 patients in the depression
      cohort and 131,912 patients in the no-depression cohort between January 1, 1998,
      and December 31, 2008, and calculated the incidence rates of newly diagnosed
      osteoporosis. We used Cox proportional hazards models to assess the effects of
      depression. The Kaplan-Meier method was applied to estimate the cumulative
      osteoporosis incidence curves. RESULTS: Patients with depression were 1.30 times
      more likely to experience osteoporosis than those without depression. The risk
      was higher for patients with severe depression and mild depression than for those
      without depression. A greater hazard ratio magnitude was observed in patients
      aged 35 to 49 years. We also observed a significant decrease in osteoporosis risk
      in patients with depression treated with antidepressant agents. CONCLUSION: The
      incidence of osteoporosis in Taiwan is associated with an a priori depression
      history. The risk was identified in both men and women, particularly in patients
      aged 35 to 49 years, and was inversely correlated with antidepressant drug
      treatment.

PMID- 25572195
TI  - Attitudes, beliefs, and practices regarding electronic nicotine delivery systems
      in patients scheduled for elective surgery.
AB  - Smokers are at increased risk of postoperative complications. Electronic nicotine
      delivery systems (ENDS; or electronic cigarettes) could be a useful tool to
      reduce harm in the perioperative period. This pilot study examined the attitudes,
      beliefs, and practices of smokers scheduled for elective surgery regarding ENDS.
      This was a cross-sectional survey of current cigarette smokers who were evaluated
      in a preoperative clinic before elective surgery at Mayo Clinic. Measures
      included demographic characteristics, smoking history, 2 indices assessing the
      perception of how smoking affected health risks, ENDS use history, and 3 indices
      assessing interest in, perceived benefits of, and barriers to using ENDS in the
      perioperative period. Of the 112 smokers who completed the survey, 62 (55%) had
      tried ENDS and 24 (21%) reported current use. The most commonly stated reason for
      using ENDS was to quit smoking. Approximately 2 in 3 participants would be
      willing to use ENDS to help them reduce or eliminate perioperative cigarette use,
      and similar proportions perceived health benefits of doing so. Of the factors
      studied, only attempted to quit within the last year was significantly associated
      with increased interest in the perioperative use of ENDS (P=.03). Compared with
      participants who had tried ENDS (n=62), those who had never tried ENDS (n=50) had
      a significantly increased interest in the perioperative use of ENDS. A
      substantial proportion of patients scheduled for elective surgery had tried ENDS
      and would consider using ENDS to reduce perioperative use of cigarettes. 

PMID- 25572193
TI  - Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other
      imaged renal masses and bladder and prostate cancer.
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of urine aquaporin 1
      (AQP1) and perilipin 2 (PLIN2) concentrations to diagnose clear cell or papillary
      renal cell carcinoma (RCC) by comparing urine concentrations of these unique
      biomarkers in patients with RCC, noncancer renal masses, bladder cancer, and
      prostate cancer. METHODS: From February 1, 2012, through October 31, 2012,
      preoperative urine samples were obtained from patients with a presumptive
      diagnosis of RCC based on an imaged renal mass, prostate cancer, or transitional
      cell bladder cancer. Imaged renal masses were diagnosed postnephrectomy-as
      malignant or benign-by histology. Urine AQP1 and PLIN2 concentrations were
      measured by using a sensitive and specific Western blot and normalized to urine
      creatinine concentration. RESULTS: Median concentrations of urine AQP1 and PLIN2
      in patients with clear cell and papillary RCC (n=47) were 29 and 36 relative
      absorbance units/mg urine creatinine, respectively. In contrast, median
      concentrations in patients with bladder cancer (n=22) and prostate cancer (n=27),
      patients with chromophobe tumors (n=7), and patients with benign renal
      oncocytomas (n=9) and angiomyolipomas (n=7) were all less than 10 relative
      absorbance units/mg urine creatinine (Kruskal-Wallis test, P<.001 vs RCC for both
      biomarkers) and comparable with those in healthy controls. The area under the
      receiver operating characteristic curve ranged from 0.99 to 1.00 for both
      biomarkers. CONCLUSION: These results support the specificity and sensitivity of
      urine AQP1 and PLIN2 concentrations for RCC. These novel tumor-specific proteins
      have high clinical validity and high potential as specific screening biomarkers
      for clear cell and papillary RCC as well as in the differential diagnosis of
      imaged renal masses. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00851994.

PMID- 25572196
TI  - Counseling patients on the use of electronic cigarettes.
AB  - Electronic cigarettes (e-cigarettes) have substantially increased in popularity.
      Clear evidence about the safety of e-cigarettes is lacking, and laboratory
      experiments and case reports suggest these products may be associated with
      potential adverse health consequences. The effectiveness of e-cigarettes for
      smoking cessation is modest and appears to be comparable to the nicotine patch
      combined with minimal behavioral support. Although a role for e-cigarettes in the
      treatment of tobacco dependence may emerge in the future, the potential risk of e
      cigarettes outweighs their known benefit as a recommended tobacco treatment
      strategy by clinicians. Patients should be counseled on the known efficacy and
      potential risks of e-cigarettes. 

PMID- 25572198
TI  - The epidemiology and economic consequences of pain.
AB  - Pain is considered a major clinical, social, and economic problem in communities
      around the world. In this review, we describe the incidence, prevalence, and
      economic burden of pain conditions in children, adolescents, and adults based on
      an electronic search of the MEDLINE and EMBASE databases for articles published
      from January 1, 2000, through August 1, 2014, using the keywords pain,
      epidemiology, burden, prevalence, and incidence. The impact of pain on
      individuals and potential risk factors are also discussed. Differences in the
      methodology and conduct of epidemiological studies make it difficult to provide
      precise estimates of prevalence and incidence; however, the burden of pain is
      unquestionably large. Improved concepts and methods are needed in order to study
      pain from a population perspective and further the development of pain prevention
      and management strategies. 

PMID- 25572197
TI  - 46-year-old man with abdominal pain and hypotension.

PMID- 25572199
TI  - Regenerative medicine and nasal surgery.
AB  - Nasal surgery is a constellation of operations that are intended to restore form
      and function to the nose. The amount of augmentation required for a given case is
      a delicate interplay between patient aesthetic desires and corrective measures
      taken for optimal nasal airflow. Traditional surgical techniques make use of
      autologous donor tissue or implanted alloplastic materials to restore nasal
      deficits. Limited availability of donor tissue and associated harvest site
      morbidity have pushed surgeons and researchers to investigate methods to
      bioengineer nasal tissues. For this article, we conducted a review of the
      literature on regenerative medicine as it pertains to nasal surgery. PubMed was
      searched for articles dating from January 1, 1994, through August 1, 2014.
      Journal articles with a focus on regenerative medicine and nasal tissue
      engineering are included in this review. Our search found that the greatest
      advancements have been in the fields of mucosal and cartilage regeneration, with
      a growing body of literature to attest to its promise. With recent advances in
      bioscaffold fabrication, bioengineered cartilage quality, and mucosal
      regeneration, the transition from comparative animal models to more expansive
      human studies is imminent. Each of these advancements has exciting implications
      for treating patients with increased efficacy, safety, and satisfaction. 

PMID- 25572200
TI  - Cardiovascular disease mortality and excessive exercise in heart attack
      survivors.

PMID- 25572201
TI  - In reply-Cardiovascular disease mortality and excessive exercise in heart attack
      survivors.

PMID- 25572202
TI  - Ethanol should be subjected to a randomized controlled trial.

PMID- 25572203
TI  - US Ebola case: an example of the misuse of antibiotics and a reminder for better
      stewardship.

PMID- 25572204
TI  - In reply-Ethanol should be subjected to a randomized controlled trial.

PMID- 25572205
TI  - Top of the basilar syndrome with disturbed consciousness.

PMID- 25572206
TI  - 60-year-old man with chronic diarrhea and peptic ulcer disease.

PMID- 25572208
TI  - Genetic differences in ksdD influence on the ADD/AD ratio of Mycobacterium
      neoaurum.
AB  - Mycobacterium neoaurum TCCC 11028 (MNR) and M. neoaurum TCCC 11028 M3 (MNR M3)
      significantly differ in the ratio of androst-1,4-diene-3,17-dione (ADD) to
      androst-4-ene-3,17-dione (AD) produced. The large fluctuations are related to the
      dehydrogenation activity of 3-ketosteroid-Delta(1)-dehydrogenase (KsdD). Analysis
      of the primary structure of KsdD showed that the Ser-138 of KsdD-MNR changed to
      Leu-138 of KsdD-MNR M3 because of C413T in the ksdD gene. This phenomenon
      directly affected KsdD activity. The effect of the primary structure of KsdD on
      dehydrogenation activity was confirmed through exogenous expression. Whole-cell
      transformation initially revealed that KsdD-MNR showed a higher dehydrogenation
      activity than KsdD-MNR M3. Then, ksdD gene replacement strain was constructed by
      homologous recombination. The results of steroid transformation experiments
      showed that the ability of the MNR M3DeltaksdD::ksdD-MNR strain to produce ADD
      was improved and it returned to the similar level of the MNR strain. This result
      indicated that the ADD/AD ratio of the two M. neoaurum strains was influenced by
      the difference in ksdD. The mechanism by which residue mutations alter enzyme
      activity may be connected with the crystal structure of KsdD from Rhodococcus
      erythropolis SQ1. As a key amino acid residue in the active center position, Ser
      138 played an important role in maintaining the active center in the hydrophobic
      environment of KsdD. This study may serve as a basis for future studies on the
      structural analysis and catalytic mechanism of dehydrogenase. 

PMID- 25572210
TI  - Geographical variation of shell thickness in the mussel Perumytilus purpuratus
      along the southeast Pacific coast.
AB  - At broad geographical scales, the variation in bivalve shell thickness can be
      modulated by environmental factors that vary with latitude, such as sea surface
      temperature (SST), seawater pH, or calcium carbonate availability. Mussels
      usually form multilayered beds, and shell thickness is also expected to be
      affected by density and layering due to intraspecific competition. In this work,
      we explored the geographical variation of shell thickness in the intertidal
      mussel Perumytilus purpuratus between 18 degrees  and 42 degrees S along the
      southeastern Pacific coast. We tested the hypothesis that there was a positive
      relationship between shell thickness and SST, and then we explored other
      variables that could have an effect on thickness, such as density, number of
      layers, and others environmental variables (pH and calcite concentration). The
      expected positive linear relationship between shell thickness and sea surface
      temperature was not found, but when the other population variables were included
      in the analysis, an unexpected inverse SST-thickness relationships appeared as
      significant, probably because this species could be adapted to colder and more
      acid seawater as are those of the tips of South America. Thickness was also
      negatively affected by density, which was expected for a gregarious species
      showing high intraspecific competition. Finally, our results highlight the
      importance of including density and crowding effects when macroscale patterns are
      explored, particularly in gregarious species, since these patterns could also be
      modulated by density-dependent processes, which might then override latitudinal
      trends of shell thickness when they are not included in the analyses. 

PMID- 25572209
TI  - Integrins of the starlet sea anemone Nematostella vectensis.
AB  - Integrins are extracellular matrix receptors composed of alpha and beta subunits.
      Here we describe two alpha subunits and four beta subunits from the starlet sea
      anemone Nematostella vectensis. Phylogenetic analysis suggests that the alpha
      subunits are most closely related to RGD- and LDV-dependent alpha subunits of
      chordates. The beta subunits cluster with the previously described beta integrins
      of the hard coral Acropora millepora. The expression of one of the alpha subunits
      and three of the beta subunits was confirmed by reverse transcription PCR and in
      situ hybridization. The alpha subunit is primarily expressed in cells near
      muscles, by a subset of gastrodermal cells, and in the gonad. The three beta
      subunits each have distinctive patterns of expression: one is concentrated in the
      gonad and mesenteric filament, another is found in a subset of cells in the
      epidermis of the oral region and in a subset of gastrodermal cells in the
      mesenteries, and a third is expressed widely. Changes in expression were also
      studied 48 h after horizontal transection by quantitative reverse transcription
      PCR and in situ hybridization. One of the beta subunits is expressed 8-fold
      higher during regeneration, and its expression is observed in cells within both
      the epidermis and the gastrodermis at the site of regeneration. Our observations
      confirm that complex patterns of integrin expression were already present in
      basal metazoans. The integrins expressed in the gonads may play roles in
      mediating sperm-egg interactions in N. vectensis, while others may play a role in
      regulating proliferation during regeneration. 

PMID- 25572211
TI  - Chemical defense against fouling in the solitary ascidian Phallusia nigra.
AB  - The solitary ascidian Phallusia nigra is rarely fouled by epibionts. Here, we
      tested the antifouling activity of its crude extracts in laboratory and field
      assays. P. nigra extracts inhibited the growth of all eight tested environmental
      bacteria and two of four laboratory bacteria. Extracts of the sympatric, but
      fouled solitary ascidian Herdmania momus inhibited only one test bacterium.
      Scanning electron microscopy confirmed that the tunic surface of P. nigra is
      largely bacteria-free. Both ascidian extracts significantly inhibited the larval
      metamorphosis of the bryozoan Bugula neritina at the tested concentration range
      of 0.05-2 mg ml(-1). Both crude extracts were toxic to larvae of the brine shrimp
      Artemia salina at natural volumetric whole-tissue concentrations, but only P.
      nigra showed activity at 2 mg ml(-1) and below (LC50 = 1.11 mg ml(-1)). P. nigra
      crude extracts also significantly reduced the settlement of barnacles,
      polychaetes, and algae in Mediterranean field assays and barnacle settlement in
      Red Sea trials. Comparisons between control experiments and pH values monitored
      in all experiments indicate that the observed effects were not due to acidity of
      the organic extracts. Our results show that P. nigra secondary metabolites have
      antifouling activities, which may act in synergy with previously proposed
      physiological antifouling mechanisms. 

PMID- 25572212
TI  - Effect of food on metamorphic competence in the model system Crepidula fornicata.
AB  - Food quality and quantity, as well as temperature, are all factors that are
      expected to affect rates of development, and are likely to be affected by
      expected climatic change. We tested the effect of a mixed diet versus a single
      food diet on metamorphic competence in the emerging model species Crepidula
      fornicata. We then compared our results with other published studies on this
      species that examined time to metamorphic competence across a range of food
      concentrations and rearing temperatures. Ours was the only study to test the
      effects of single food versus a mixed diet on metamorphic competence for this
      species. Diet composition did not affect metamorphic competence or survivorship.
      Comparing results across studies, we found that the shortest time to metamorphic
      competence was typically found when the food availability per larva was the
      greatest, independent of rearing temperature. Unfortunately, some published
      studies did not include important metadata needed for comparison with other
      studies; these data included larval rearing density, food density, frequency of
      feeding, and rearing temperature. Mortality rates were not always reported and
      when reported were often measured in different ways, preventing comparison. Such
      metadata are essential for comparisons among studies as well as among taxa, and
      for the determination of generalizable patterns and evolutionary trends.
      Increased reporting of all such metadata is essential if we are to use scientific
      studies performed to their fullest potential. 

PMID- 25572213
TI  - Immunolocalization of a voltage-gated calcium channel beta subunit in the
      tentacles and cnidocytes of the Portuguese man-of-war, Physalia physalis.
AB  - This study investigated the localization of a voltage-gated calcium channel
      (VGCC) beta subunit in the tentacles and cnidocytes of the Portuguese man-of-war
      using confocal immunocytochemistry. An antibody specific to the Ca(2+) channel
      beta subunit of the Portuguese-man-of-war (PpCaVbeta) was generated, and
      characterized by Western immunoblotting. The antibody labeling was widespread in
      the ectoderm of cnidosacs of the tentacles. The binding of the antibody on
      isolated cnidocytes was distributed at the base of the cell and appeared as
      multiple strong fluorescent plaques located around the basal hemisphere of the
      cell. The distribution of PpCaVbeta in the cnidocyte is consistent with previous
      studies on other hydrozoans that demonstrated that cnidocytes convey sensory
      information to other cnidocytes through chemical synapses in which the cnidocyte
      is pre-synaptic to elements of the animal's nervous system. Importantly and
      surprisingly, PpCaVbeta did not localize to the apical surface of the cnidocyte
      where the exocytotic events involved in cnidocyst discharge are thought to take
      place. 

PMID- 25572215
TI  - Multiple conducting systems in the cubomedusa Carybdea marsupialis.
AB  - Acute responses to mechanical, electrical, and photic stimuli were used to
      describe neural conducting systems in the cubomedusan jellyfish Carybdea
      marsupialis underlying three behaviors: contractile responses of single
      tentacles, protective crumple responses, and alterations of swimming activity by
      the visual system. Responses of single tentacles consisted of tentacular
      shortening and inward pedalial bending, and were accompanied by bursts of
      extracellularly recorded spike activity that were restricted to the stimulated
      tentacle. With nociceptive stimuli delivered to the subumbrella or margin, all
      four tentacles produced similar responses in a crumple response. The spike bursts
      in all four tentacles showed coordinated firing as long as the nerve ring was
      intact. Crumples were still produced following cuts through the nerve ring, but
      the activity in individual tentacles was no longer coordinated. Responses to
      light-on stimulation of a rhopalium, as recorded from the pacemaker region, were
      weak and inconsistent, but when present, resulted in a stimulation of swimming
      activity. In comparison, light-off responses were robust and resulted in
      temporary inhibition of swimming activity. Light-off responses were conducted in
      the nerve ring to unstimulated rhopalia. In conclusion, three conducting systems
      have been described as components of the rhopalia-nerve ring centralized system
      in Carybdea: the swim motor system, the crumple coordination system, and the
      light-off response system. 

PMID- 25572214
TI  - Circadian rhythms of crawling and swimming in the nudibranch mollusc Melibe
      leonina.
AB  - Daily rhythms of activity driven by circadian clocks are expressed by many
      organisms, including molluscs. We initiated this study, with the nudibranch
      Melibe leonina, with four goals in mind: (1) determine which behaviors are
      expressed with a daily rhythm; (2) investigate which of these rhythmic behaviors
      are controlled by a circadian clock; (3) determine if a circadian clock is
      associated with the eyes or optic ganglia of Melibe, as it is in several other
      gastropods; and (4) test the hypothesis that Melibe can use extraocular
      photoreceptors to synchronize its daily rhythms to natural light-dark cycles. To
      address these goals, we analyzed the behavior of 55 animals exposed to either
      artificial or natural light-dark cycles, followed by constant darkness. We also
      repeated this experiment using 10 animals that had their eyes removed.
      Individuals did not express daily rhythms of feeding, but they swam and crawled
      more at night. This pattern of locomotion persisted in constant darkness,
      indicating the presence of a circadian clock. Eyeless animals also expressed a
      daily rhythm of locomotion, with more locomotion at night. The fact that eyeless
      animals synchronized their locomotion to the light-dark cycle suggests that they
      can detect light using extraocular photoreceptors. However, in constant darkness,
      these rhythms deteriorated, suggesting that the clock neurons that influence
      locomotion may be located in, or near, the eyes. Thus, locomotion in Melibe
      appears to be influenced by both ocular and extraocular photoreceptors, although
      the former appear to have a greater influence on the expression of circadian
      rhythms. 

PMID- 25572216
TI  - Functional characterization of neuroendocrine regulation of branchial carbonic
      anhydrase induction in the euryhaline crab Callinectes sapidus.
AB  - Carbonic anhydrase (CA) plays an essential role as a provider of counterions for
      Na(+)/H(+) and Cl(-)/HCO3 (-) exchange in branchial ionic uptake processes in
      euryhaline crustaceans. CA activity and gene expression are low in crabs
      acclimated to full-strength seawater, with transfer to low salinity resulting in
      large-scale inductions of mRNA and subsequent enzyme activity in the posterior
      ion-regulating gills (e.g., G7). In the green crab Carcinus maenas, CA has been
      shown to be under inhibitory neuroendocrine control by a putative hormone in the
      x-organ-sinus gland complex (XOSG), located in the eyestalk. This study
      characterizes the neuroendocrine regulation of CA induction in the blue crab
      Callinectes sapidus, a commonly used experimental organism for crustacean
      osmoregulation. In crabs acclimated to full-strength seawater, eyestalk ligation
      (ESL) triggered a 1.8- and 100-fold increase in CA activity and mRNA,
      respectively. Re-injection with eyestalk homogenates abolished increases in CA
      activity and fractionally reduced CA gene expression. ESL also enhanced CA
      induction by 33% after 96 h in crabs transferred to 15 ppt salinity. Injection of
      eyestalk homogenates into intact crabs transferred from 35 to 15 ppt diminished
      by 43% the CA induction stimulated by low salinity. These results point to the
      presence of a repressor hormone in the eyestalk. Separate injections of medullary
      tissue (MT) and sinus gland (SG), two components of the eyestalk, reduced
      salinity-stimulated CA activity by 22% and 49%, suggesting that the putative
      repressor is localized to the SG. Crabs injected with SG extract harvested from
      crabs acclimated to 5 ppt showed no decrease in CA activity, demonstrating that
      the hormone is down-regulated at low salinity. Our results show the presence in
      the XOSG of an inhibitory compound that regulates salinity-stimulated CA
      induction. 

PMID- 25572217
TI  - FISH labeling reveals a horizontally transferred algal (Vaucheria litorea)
      nuclear gene on a sea slug (Elysia chlorotica) chromosome.
AB  - The horizontal transfer of functional nuclear genes, coding for both chloroplast
      proteins and chlorophyll synthesis, from the food alga Vaucheria litorea to the
      sea slug Elysia chlorotica has been demonstrated by pharmacological, polymerase
      chain reaction (PCR), real time PCR (qRT-PCR), and transcriptome sequencing
      experiments. However, partial genomic sequencing of E. chlorotica larvae failed
      to find evidence for gene transfer. Here, we have used fluorescent in situ
      hybridization to localize an algal nuclear gene, prk, found in both larval and
      adult slug DNA by PCR and in adult RNA by transcriptome sequencing and RT-PCR.
      The prk probe hybridized with a metaphase chromosome in slug larvae, confirming
      gene transfer between alga and slug. 

PMID- 25572219
TI  - Cotranslational protein folding reveals the selective use of synonymous codons
      along the coding sequence of a low expression gene.

PMID- 25572220
TI  - An overview of wheat genome sequencing and its implications for crop improvement.

PMID- 25572221
TI  - Genetic analysis to identify good combiners for ToLCV resistance and yield
      components in tomato using interspecific hybridization.
AB  - The interspecific hybridization for tomato leaf curl virus (ToLCV) resistance was
      carried out among 10 genetically diverse tomato genotypes (diversified by 50 SSR
      markers). Among the 10 parents, four susceptible cultivars of Solanum
      lycopersicum were crossed with six resistant wilds, such as S. pimpinellifolium,
      S. habrochaites, S. chemielewskii, S. ceraseforme, S. peruvianum and S. chilense
      in a line x tester mating design. All the 24 hybrids and their parents were grown
      in the field and glasshouse conditions to determine the general-combining
      abilities (GCA) and specific-combining abilities (SCA). The variances due to SCA
      and GCA showed both additive and nonadditive gene effects. Based on GCA
      estimates, EC-520061 and WIR-5032 were good general combiners while based on SCA
      estimates, PBC x EC-520061 and PBC x EC-521080 were best specific combiners for
      coefficient of infection and fruit yield per plant in both the environments.
      These lines could be selected and utilized in ToLCV resistance and high yield
      breeding programme for improving the traits.

PMID- 25572223
TI  - Mapping and introgression of QTL for yield and related traits in two backcross
      populations derived from Oryza sativa cv. Swarna and two accessions of O. nivara.
AB  - Advanced backcross QTL (AB-QTL) analysis was carried out in two Oryza nivara
      derived BC2F2 populations. For nine traits, we identified 28 QTL in population 1
      and 26 QTL in population 2. The two most significant yield-enhancing QTL, yldp9.1
      and yldp2.1 showed an additive effect of 16 and 7 g per plant in population 1,
      while yld2.1 and yld11.1 showed an additive effect of 11 and 10 g per plant in
      population 2. At least one O. nivara-derived QTL with a phenotypic variance of
      >15% was detected for seven traits in population 1 and three traits in population
      2. The O. nivara-derived QTL ph1.1, nt12.1, nsp1.1, nfg1.1, bm11.1, yld2.1 and
      yld11.1 were conserved at the same chromosomal locations in both populations. Two
      major QTL clusters were detected at the marker intervals RM488-RM431 and RM6
      RM535 on chromosomes 1 and 2, respectively. The colocation of O. nivara-derived
      yield QTL with yield meta-QTL on chromosomes 1, 2 and 9 indicates their accuracy
      and consistency. The major-effect QTL reported in this study are useful for
      marker-assisted breeding and are also suitable for further fine mapping and
      candidate gene identification. 

PMID- 25572222
TI  - Complete nucleotide sequence and gene rearrangement of the mitochondrial genome
      of Occidozyga martensii.
AB  - In this study, the complete nucleotide sequence (18,321 bp) of the mitochondrial
      (mt) genome of the round-tongued floating frog, Occidozyga martensii was
      determined. Although, the base composition and codon usage of O. martensii
      conformed to the typical vertebrate patterns, this mt genome contained 23 tRNAs
      (a tandem duplication of tRNA-Met gene). The LTPF tRNA-gene cluster, and the
      derived position of the ND5 gene downstream of the control region, were present
      in this mitogenome. Moreover, we found that in the WANCY tRNA-gene cluster, the
      tRNA-Asn gene was located between the tRNATyr and COI genes instead of between
      the tRNA-Ala and tRNA-Cys genes, which is a novel mtDNA gene rearrangement in
      vertebrates. Based on the concatenated nucleotide sequences of the 13 protein
      coding genes, phylogenetic analysis (BI, ML, MP) was performed to further clarify
      the phylogenetic relations of this species within anurans. 

PMID- 25572224
TI  - Identification and characterization of the RCI2 gene family in maize (Zea mays).
AB  - Rare-cold-inducible (RCI2) genes are structurally conserved members that encode
      small, highly hydrophobic proteins involved in response to various abiotic
      stresses. Phylogenetic and functional analyses of these genes have been conducted
      in Arabidopsis, but an extensive investigation of the RCI2 gene family has not
      yet been carried out in maize. In the present study, 10 RCI2 genes were
      identified in a fully sequenced maize genome. Structural characterization and
      expression pattern analysis of 10 ZmRCI2s (Zea mays RCI2 genes) were subsequently
      determined. Sequence and phylogenetic analyses indicated that ZmRCI2s are highly
      conserved, and most of them could be grouped with their orthologues from other
      organisms. Chromosomal location analysis indicated that ZmRCI2s were distributed
      unevenly on seven chromosomes with two segmental duplication events, suggesting
      that maize RCI2 gene family is an evolutionarily conserved family. Putative
      stress-responsive cis-elements were detected in the 2-kb promoter regions of the
      10 ZmRCI2s. In addition, the 10 ZmRCI2s showed different expression patterns in
      maize development based on transcriptome analysis. Further, microarray and
      quantitative real-time PCR (qRT-PCR) analysis showed that each maize RCI2 genes
      were responsive to drought stress, suggesting their important roles in drought
      stress response. The results of this work provide a basis for future cloning and
      application studies of maize RCI2 genes. 

PMID- 25572225
TI  - F1 hybrids of BALB/c and C57BL/6 mouse strains respond differently to low-dose
      ionizing radiation exposure.
AB  - There are evidences to show that response to ionizing radiations have genetic
      influence. To investigate this further, reciprocal F1 hybrids were generated by
      crossbreeding the radiation-susceptible BALB/c mouse strain with resistant
      C57BL/6 in a sex-specific manner (BALB/c? x C57BL/6? = B6BcF1; C57BL/6? x BALB/c?
      =BcB6F1). These hybrids were compared with each other and to the parental strains
      with respect to transcriptional responses to low-dose ionizing radiation exposure
      (LDIR). The two F1 hybrids showed drastic differences in their gene expression
      profiles to ionizing radiation exposure particularly in case of the genes
      involved in DNA damage response and repair process. Also, the inheritance pattern
      of the gene expression was found to be complex and could not be explained solely
      on the basis of parental expression pattern. It was concluded that there is a
      differential transmission of susceptible trait alleles from the parents to F1
      progeny which is dependent on the sex of the parent mouse strain used to set up
      the crosses and other environmental factors.

PMID- 25572226
TI  - Phosphate acquisition efficiency and phosphate starvation tolerance locus
      (PSTOL1) in rice.
AB  - Phosphate availability is a major factor limiting tillering, grain filling vis-a
      vis productivity of rice. Rice is often cultivated in soil like red and lateritic
      or acid, with low soluble phosphate content. To identify the best genotype
      suitable for these types of soils, P acquisition efficiency was estimated from
      108 genotypes. Gobindabhog, Tulaipanji, Radhunipagal and Raghusail accumulated
      almost equal amounts of phosphate even when they were grown on P-sufficient soil.
      Here, we have reported the presence as well as the expression of a previously
      characterized rice gene, phosphate starvation tolerance locus (PSTOL1) in a set
      of selected genotypes. Two of four genotypes did not show any detectable
      expression but carried the gene. One mega cultivar, Swarna did not possess this
      gene but showed high P-deficiency tolerance ability. Increase of root biomass,
      not length, in P-limiting situations might be considered as one of the selecting
      criteria at the seedling stage. Neither the presence of PSTOL1 gene nor its
      closely-linked SSR RM1261, showed any association with P-deficiency tolerance
      among the 108 genotypes. Not only this, but the presence of PSTOL1 in recombinant
      inbred line (RIL) developed from a cross between Gobindabhog and Satabdi, also
      did not show any linkage with P-deficiency tolerance ability. Thus, before
      considering PSTOL1 gene in MAB, its expression and role in P-deficiency tolerance
      in the donor parent must be ascertained. 

PMID- 25572227
TI  - Construction of an EST-SSR-based interspecific transcriptome linkage map of fibre
      development in cotton.
AB  - Quantitative trait locus (QTL) mapping is an important method in marker-assisted
      selection breeding. Many studies on the QTLs focus on cotton fibre yield and
      quality; however, most are conducted at the DNA level, which may reveal null
      QTLs. Hence, QTL mapping based on transcriptome maps at the cDNA level is often
      more reliable. In this study, an interspecific transcriptome map of
      allotetraploid cotton was developed based on an F2 population (Emian22 x 3-79) by
      amplifying cDNA using EST-SSRs. The map was constructed using cDNA obtained from
      developing fibres at five days post anthesis (DPA). A total of 1270 EST-SSRs were
      screened for polymorphisms between the mapping parents. The resulting
      transcriptome linkage map contained 242 markers that were distributed in 32
      linkage groups (26 chromosomes). The full length of this map is 1938.72 cM with a
      mean marker distance of 8.01 cM. The functions of some ESTs have been annotated
      by exploring homologous sequences. Some markers were related to the
      differentiation and elongation of cotton fibre, while most were related to the
      basic metabolism. This study demonstrates that constructing a transcriptome
      linkage map by amplifying cDNAs using EST-SSRs is a simple and practical method
      as well as a powerful tool to map eQTLs for fibre quality and other traits in
      cotton. 

PMID- 25572228
TI  - The complete mitochondrial genome of the yellow-browed bunting, Emberiza
      chrysophrys (Passeriformes: Emberizidae), and phylogenetic relationships within
      the genus Emberiza.
AB  - Mitochondrial genomes have proved to be powerful tools in resolving phylogenetic
      relationships. Emberiza chrysophrys (least concern species: IUCN 2013) is a
      passerine bird in the bunting family, Emberizidae. The complete mitochondrial
      genome of E. chrysophrys was sequenced. This circular mitochondrial genome was
      16,803 bp in length, with an A+T content of 52.26%, containing 13 protein-coding
      genes (PCGs), two rRNAs, 22 tRNAs and a putative control region (CR). The CR of
      E. chrysophrys was divided into three conserved domains. Six conserved sequence
      boxes in the central conserved domain II were identified as F, E, D, C, b and B.
      An obvious positive AT-skew and negative GC-skew bias were found for all 28 genes
      encoded by the H strand, whereas it was the reverse in the remaining nine genes
      encoded by the L strand. Remarkable rate heterogeneity was present in the
      mitochondrial genome of E. chrysophrys. Notably, unusual slow rate of evolution
      in the mitochondrial CR of E. chrysophrys was detected, which is rarely seen in
      other birds. Phylogenetic analyses were carried out based on 13 PCGs that showed
      E. pusilla was the sister group of E. rustica, and the monophyly of Emberiza was
      established. 

PMID- 25572229
TI  - Expression of the rgMT gene, encoding for a rice metallothionein-like protein in
      Saccharomyces cerevisiae and Arabidopsis thaliana.
AB  - Metallothioneins (MTs) are cysteine-rich proteins of low molecular weight with
      many attributed functions, such as providing protection against metal toxicity,
      being involved in regulation of metal ions uptake that can impact plant
      physiology and providing protection against oxidative stress. However, the
      precise function of the metallothionein-like proteins such as the one coded for
      rgMT gene isolated from rice (Oryza sativa L.) is not completely understood. The
      whole genome analysis of rice (O. sativa) showed that the rgMT gene is homologue
      to the Os11g47809 on chromosome 11 of O. sativa sp. japonica genome. This study
      used the rgMT coding sequence to create transgenic lines to investigate the
      subcellular localization of the protein, as well as the impact of gene expression
      in yeast (Saccharomyces cerevisiae) and Arabidopsis thaliana under heavy metal
      ion, salt and oxidative stresses. The results indicate that the rgMT gene was
      expressed in the cytoplasm of transgenic cells. Yeast cells transgenic for rgMT
      showed vigorous growth compared to the nontransgenic controls when exposed to 7
      mM CuCl2, 10 mM FeCl2, 1 M NaCl, 24 mM NaHCO3 and 3.2 mM H2O2, but there was no
      significant difference for other stresses tested. Similarly, Arabidopsis
      transgenic for rgMT displayed significantly improved seed germination rates over
      that of the control when the seeds were stressed with 100 MUM CuCl2 or 1 mM H2O2.
      Increased biomass was observed in the presence of 100 MUM CuCl2, 220 MUM FeCl2, 3
      mM Na2CO3, 5 mM NaHCO3 or 1 mM H2O2. These results indicate that the expression
      of the rice rgMT gene in transgenic yeast and Arabidopsis is implicated in
      improving their tolerance for certain salt and peroxide stressors.

PMID- 25572230
TI  - Association of PPARgamma gene polymorphisms with osteoarthritis in a southeast
      Chinese population.
AB  - Primary osteoarthritis (OA) is a leading cause of disability in developed
      countries. Currently no satisfactory treatment to stop disease progression
      exists. Recent studies suggest that activation of the transcription factor
      peroxisome proliferator-activated receptor gamma (PPARgamma) is an interesting
      therapeutic target for this disease. PPARgamma is a transcription factor
      important for adipogenesis and adipocyte differentiation. Agonists of PPARgamma
      inhibit inflammation and reduce generation of cartilage degradation products both
      in vitro and in vivo, and reduce the development/progression of cartilage lesions
      in OA animal models. However, there are no studies to assess the role of
      PPARgamma in OA susceptibility of human peripheral joints in a Chinese
      population. We conducted a case-control study in a southeast Chinese population
      to determine the association of PPARgamma gene polymorphisms (rs1801282,
      rs12629751, rs2292101, rs4135275 and rs1175543) with OA. One-hundred knee OA
      cases and 100 controls were studied. Statistically significant differences were
      detected in genotype and allele frequencies between OA and control groups in this
      population. For knee OA, the highest risk was associated with the variant allele
      T of the single nucleotide polymorphism rs12629751 (odds ratio (OR): 0.341, 95%
      confidence interval (CI):0.173-0.673, P = 0.002), and allele T of SNP rs12629751
      (chi-square: 9.546, P = 0.002) could be considered as a risk factor of knee OA.
      Therefore, PPARgamma mutation could be associated with the incidence of OA in a
      Chinese population. There is a significant association between the PPARgamma
      polymorphism rs12629751 and susceptibility to knee OA in a southeast Chinese
      population. 

PMID- 25572231
TI  - Characterization and phylogenetic analysis of alpha-gliadin gene sequences
      reveals significant genomic divergence in Triticeae species.
AB  - Although the unique properties of wheat alpha-gliadin gene family are well
      characterized, little is known about the evolution and genomic divergence of
      alpha-gliadin gene family within the Triticeae. We isolated a total of 203 alpha
      gliadin gene sequences from 11 representative diploid and polyploid Triticeae
      species, and found 108 sequences putatively functional. Our results indicate that
      alpha-gliadin genes may have possibly originated from wild Secale species, where
      the sequences contain the shortest repetitive domains and display minimum
      variation. A miniature inverted-repeat transposable element insertion is reported
      for the first time in alpha-gliadin gene sequence of Thinopyrum intermedium in
      this study, indicating that the transposable element might have contributed to
      the diversification of alpha-gliadin genes family among Triticeae genomes. The
      phylogenetic analyses revealed that the alpha-gliadin gene sequences of
      Dasypyrum, Australopyrum, Lophopyrum, Eremopyrum and Pseudoroengeria species have
      amplified several times. A search for four typical toxic epitopes for celiac
      disease within the Triticeae alpha-gliadin gene sequences showed that the alpha
      gliadins of wild Secale, Australopyrum and Agropyron genomes lack all four
      epitopes, while other Triticeae species have accumulated these epitopes,
      suggesting that the evolution of these toxic epitopes sequences occurred during
      the course of speciation, domestication or polyploidization of Triticeae. 

PMID- 25572232
TI  - Genomewide analysis of TCP transcription factor gene family in Malus domestica.
AB  - Teosinte branched 1/cycloidea/proliferating cell factor 1 (TCP) proteins are a
      large family of transcriptional regulators in angiosperms. They are involved in
      various biological processes, including development and plant metabolism
      pathways. In this study, a total of 52 TCP genes were identified in apple (Malus
      domestica) genome. Bioinformatic methods were employed to predicate and analyse
      their relevant gene classification, gene structure, chromosome location, sequence
      alignment and conserved domains of MdTCP proteins. Expression analysis from
      microarray data showed that the expression levels of 28 and 51 MdTCP genes
      changed during the ripening and rootstock-scion interaction processes,
      respectively. The expression patterns of 12 selected MdTCP genes were analysed in
      different tissues and in response to abiotic stresses. All of the selected genes
      were detected in at least one of the tissues tested, and most of them were
      modulated by adverse treatments indicating that the MdTCPs were involved in
      various developmental and physiological processes. To the best of our knowledge,
      this is the first study of a genomewide analysis of apple TCP gene family. These
      results provide valuable information for studies on functions of the TCP
      transcription factor genes in apple. 

PMID- 25572233
TI  - Pear 14-3-3a gene (Pp14-3-3a) is regulated during fruit ripening and senescense,
      and involved in response to salicylic acid and ethylene signalling.
AB  - 14-3-3 proteins play important roles in regulating plant development and
      phytohormone (abscisic acid, gibberellin and brassinosteroids) signalling.
      However, their regulation in fruit ripening and senescense, and response to
      salicylic acid and ethylene signalling are yet to be illustrated. One cDNA
      encoding putative 14-3-3 protein was isolated from pear (Pyrus pyrifolia) and
      designated Pp14-3-3a. Phylogenetic analysis clearly demonstrated that Pp14-3-3a
      belonged to epsilon-like group of 14-3-3 superfamilies. Real-time quantitative
      PCR analysis indicated that the expression of Pp14-3-3a gene was developmentally
      regulated in the fruit. Further study demonstrated that Pp14-3-3a expression was
      inhibited by salicylic acid and induced by ethylene precursor 1-aminocyclopropane
      1-carboxylic acid in pear fruit. These data suggested that Pp14-3-3a might be
      involved in response to salicylic acid and ethylene signalling during fruit
      ripening and senescence of pear. 

PMID- 25572234
TI  - Positive selection in the leucine-rich repeat domain of Gro1 genes in Solanum
      species.
AB  - In pathogen resistant plants, solvent-exposed residues in the leucine-rich repeat
      (LRR) proteins are thought to mediate resistance by recognizing plant pathogen
      elicitors. In potato, the gene Gro1-4 confers resistance to Globodera
      rostochiensis. The investigation of variability in different copies of this gene
      represents a good model for the verification of positive selection mechanisms.
      Two datasets of Gro1 LRR sequences were constructed, one derived from the Gro1-4
      gene, belonging to different cultivated and wild Solanum species, and the other
      belonging to paralogues of a resistant genotype. Analysis of nonsynonymous to
      synonymous substitution rates (K(a)/K(s)) highlighted 14 and six amino acids with
      K(a)/K(s) >1 in orthologue and paralogue datasets, respectively. Selection
      analysis revealed that the leucine-rich regions accumulate variability in a very
      specific way, and we found that some combinations of amino acids in these sites
      might be involved in pathogen recognition. The results confirm previous studies
      on positive selection in the LRR domain of R protein in Arabidopsis and other
      model plants and extend these to wild Solanum species. Moreover, positively
      selected sites in the Gro1 LRR domain show that coevolution mainly occurred in
      two regions on the internal surface of the three-dimensional horseshoe structure
      of the domain, albeit with different evolutionary forces between paralogues and
      orthologues.

PMID- 25572235
TI  - Comparative analysis of ADS gene promoter in seven Artemisia species.
AB  - Artemisinin is the most effective antimalarial drug that is derived from
      Artemisia annua. Amorpha-4,11-diene synthase (ADS) controls the first committed
      step in artemisinin biosynthesis. The ADS gene expression is regulated by
      transcription factors which bind to the cis-acting elements on the ADS promoter
      and are probably responsible for the ADS gene expression difference in the
      Artemisia species. To identify the elements that are significantly involved in
      ADS gene expression, the ADS gene promoter of the seven Artemisia species was
      isolated and comparative analysis was performed on the ADS promoter sequences of
      these species. Results revealed that some of the cis-elements were unique or in
      terms of number were more in the high artemisinin producer species, A. annua,
      than the other species. We have reported that the light-responsive elements, W
      box, CAAT-box, 5'-UTR py-rich stretch, TATA-box sequence and tandem repeat
      sequences have been identified as important factors in the increased expression
      of ADS gene. 

PMID- 25572236
TI  - Population structure and association mapping studies for important agronomic
      traits in soybean.
AB  - The present study was carried out with a set of 96 diverse soybean genotypes with
      the objectives of analysing the population structure and to identify molecular
      markers associated with important agronomic traits. Large phenotypic variability
      was observed for the agronomic traits under study indicating suitability of the
      genotypes for association studies. The maximum values for plant height, pods per
      plant, seeds per pod, 100-seed weight and seed yield per plant were approximately
      two and half to three times more than the minimum values for the genotypes. Seed
      yield per plant was found to be significantly correlated with pods per plant (r =
      0.77), 100-seed weight (r = 0.35) and days to maturity (r = 0.23). The population
      structure studies depicted the presence of seven subpopulations which nearly
      corresponded with the source of geographical origin of the genotypes. Linkage
      disequilibrium (LD) between the linked markers decreased with the increased
      distance, and a substantial drop in LD decay values was observed between 30 and
      35 cM. Genomewide marker-traits association analysis carried out using general
      linear (GLM) and mixed linear models (MLM) identified six genomic regions (two of
      them were common in both) on chromosomes 6, 7, 8, 13, 15 and 17, which were found
      to be significantly associated with various important traits viz., plant height,
      pods per plant, 100-seed weight, plant growth habit, average number of seeds per
      pod, days to 50% flowering and days to maturity. The phenotypic variation
      explained by these loci ranged from 6.09 to 13.18% and 4.25 to 9.01% in the GLM
      and MLM studies, respectively. In conclusion, association mapping (AM) in soybean
      could be a viable alternative to conventional QTL mapping approach. 

PMID- 25572237
TI  - Genomewide identification and expression analysis of the ARF gene family in
      apple.
AB  - Auxin response factors (ARF) are transcription factors that regulate auxin
      responses in plants. Although the genomewide analysis of this family has been
      performed in some species, little is known regarding ARF genes in apple (Malus
      domestica). In this study, 31 putative apple ARF genes have been identified and
      located within the apple genome. The phylogenetic analysis revealed that MdARFs
      could be divided into three subfamilies (groups I, II and III). The predicted
      MdARFs were distributed across 15 of 17 chromosomes with different densities. In
      addition, the analysis of exon-intron junctions and of the intron phase inside
      the predicted coding region of each candidate gene has revealed high levels of
      conservation within and between phylogenetic groups. Expression profile analyses
      of MdARF genes were performed in different tissues (root, stem, leaf, flower and
      fruit), and all the selected genes were expressed in at least one of the tissues
      that were tested, which indicated that MdARFs are involved in various aspects of
      physiological and developmental processes of apple. To our knowledge, this report
      is the first to provide a genomewide analysis of the apple ARF gene family. This
      study provides valuable information for understanding the classification and
      putative functions of the ARF signal in apple. 

PMID- 25572238
TI  - Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and 11-beta
      hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension
      in the population of Odisha, India.
AB  - Essential hypertension which accounts 90-95% of the total hypertension cases is
      affected by both genetic and environmental factors. This study was undertaken to
      investigate the association of aldosterone synthase C-344T, angiotensin II type I
      receptor A1166C and 11- hydroxysteroid dehydrogenase type 2 G534A polymorphisms
      with essential hypertension in the population of Odisha, India. A total of 246
      hypertensive subjects (males, 159; females, 87) and 274 normal healthy
      individuals (males, 158; females, 116) were enrolled in this study based on the
      inclusion and exclusion criteria. Analysis of genetic and biochemical data
      revealed that in this population the CT and TT genotypes of aldosterone synthase
      C-344T polymorphism, frequency of alcohol consumption and aldosterone levels were
      significantly high among the total as well as male hypertensives, while the AC
      and CC genotypes of angiotensin II type I receptor A1166C polymorphism were
      significantly high among the total as well as female hypertensives. High density
      lipoprotein levels were higher in male hypertensives. 

PMID- 25572239
TI  - Identification of a novel SHOX mutation in a Chinese family with isolated
      Madelung deformity.

PMID- 25572240
TI  - Polymorphisms of interleukin-31 are associated with anti-CCP levels in females
      with rheumatoid arthritis.

PMID- 25572241
TI  - De novo Xp terminal deletion in a triple X female with recurrent spontaneous
      abortions: a case report.

PMID- 25572242
TI  - Are mini DNA-barcodes sufficiently informative to resolve species identities? An
      in silico analysis using Phyllanthus.

PMID- 25572243
TI  - Associations of POU1F1 gene polymorphisms and protein structure changes with
      growth traits and blood metabolites in two Iranian sheep breeds.

PMID- 25572244
TI  - A novel mutation of the USH2C (GPR98) gene in an Iranian family with Usher
      syndrome type II.

PMID- 25572245
TI  - First report of a novel LMNA mutation in a Chinese family with limb-girdle
      muscular dystrophy.

PMID- 25572246
TI  - Genetic relationships among buckwheat (Fagopyrum) species from southwest China
      based on chloroplast and nuclear SSR markers.

PMID- 25572247
TI  - Alport syndrome in a Kazakh family: a case study.

PMID- 25572248
TI  - A novel splice-site mutation in ATP6V0A4 gene in two brothers with distal renal
      tubular acidosis from a consanguineous Tunisian family.

PMID- 25572249
TI  - Overlap of Patau and Pierre Robin syndromes along with abnormal metabolism: an
      interesting case study.

PMID- 25572250
TI  - De novo dir dup/del of 18q characterized by SNP arrays and FISH in a girl child
      with mixed phenotypes.

PMID- 25572251
TI  - Development of male-specific SCAR marker in Garcinia morella (Gaertn.) Desr.

PMID- 25572254
TI  - Personal genomes, participatory genomics and the anonymity-privacy conundrum.

PMID- 25572252
TI  - Molecular and genetic basis of depression.
AB  - Joyousness or sadness is normal reaction to state of life. If any of these lead
      to certain semi-permanent changes in daily life, then it is termed as mental
      disorder. Depression is one of the mental disorders with a state of low mood and
      aversion to activities that exerts a negative effect on a person's thoughts and
      behaviour. Adolescent group is probably the world's largest active group of
      people, who are getting prone to this state of mind leading to their diminished
      mental and physical abilities. Depression is closely linked to stress and thus a
      chronic stressful life can increase the risk of depression. Depression is a
      complex disease having both genetic and environmental components as contributing
      factors. In this study an attempt has been made to put forward the understanding
      of the known genes and their functional relationships with depression and stress
      with special reference to BDNF and 5-HTTLPR. Analysis of common genetic variants
      associated with depression, especially in the members of a family who had a
      previous history, might help in identifying the individuals at risk prior to the
      onset of depression. 

PMID- 25572253
TI  - Genetic basis of interindividual susceptibility to cancer cachexia: selection of
      potential candidate gene polymorphisms for association studies.
AB  - Cancer cachexia is a complex and multifactorial disease. Evolving definitions
      highlight the fact that a diverse range of biological processes contribute to
      cancer cachexia. Part of the variation in who will and who will not develop
      cancer cachexia may be genetically determined. As new definitions,
      classifications and biological targets continue to evolve, there is a need for
      reappraisal of the literature for future candidate association studies. This
      review summarizes genes identified or implicated as well as putative candidate
      genes contributing to cachexia, identified through diverse technology platforms
      and model systems to further guide association studies. A systematic search
      covering 1986-2012 was performed for potential candidate genes / genetic
      polymorphisms relating to cancer cachexia. All candidate genes were reviewed for
      functional polymorphisms or clinically significant polymorphisms associated with
      cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used
      to reveal possible network associations between genes. Functionality of
      SNPs/genes was explored based on published literature, algorithms for detecting
      putative deleterious SNPs and interrogating the database for expression of
      quantitative trait loci (eQTLs). A total of 154 genes associated with cancer
      cachexia were identified and explored for functional polymorphisms. Of these 154
      genes, 119 had a combined total of 281 polymorphisms with functional and/or
      clinical significance in terms of cachexia associated with them. Of these, 80
      polymorphisms (in 51 genes) were replicated in more than one study with 24
      polymorphisms found to influence two or more hallmarks of cachexia (i.e.,
      inflammation, loss of fat mass and/or lean mass and reduced survival). Selection
      of candidate genes and polymorphisms is a key element of multigene study design.
      The present study provides a contemporary basis to select genes and/or
      polymorphisms for further association studies in cancer cachexia, and to develop
      their potential as susceptibility biomarkers of cachexia. 

PMID- 25572257
TI  - A carbon fiber-ZnS nanocomposite for dual application as an efficient cold
      cathode as well as a luminescent anode for display technology.
AB  - In the current work we present a simple technique to develop a carbon nanofiber
      (CNF)/zinc sulfide (ZnS) composite material for excellent FED application. CNFs
      and ZnS microspheres were synthesized by following a simple thermal chemical
      vapor deposition and hydrothermal procedure, respectively. A rigorous chemical
      mixture of CNF and ZnS was prepared to produce the CNF-ZnS composite material.
      The cathodo-luminescence intensity of the composite improved immensely compared
      to pure ZnS, also the composite material showed better field emission than pure
      CNFs. For pure CNF the turn-on field was found to be 2.1 V MUm(-1) whereas for
      the CNF-ZnS composite it reduced to a value of 1.72 V MUm(-1). Altogether the
      composite happened to be an ideal element for both the anode and cathode of a FED
      system. Furthermore, simulation of our CNF-ZnS composite system using the finite
      element modeling method also ensured the betterment of field emission from CNF
      after surface attachment of ZnS nanoclusters. 

PMID- 25572256
TI  - Insulin secretion in patients with latent autoimmune diabetes (LADA): half way
      between type 1 and type 2 diabetes: action LADA 9.
AB  - BACKGROUND: The study of endogenous insulin secretion may provide relevant
      insight into the comparison of the natural history of adult onset latent
      autoimmune diabetes (LADA) with types 1 and 2 diabetes mellitus. The aim of this
      study was to compare the results of the C-peptide response to mixed-meal
      stimulation in LADA patients with different disease durations and subjects with
      type 2 and adult-onset type 1 diabetes. METHODS: Stimulated C-peptide secretion
      was assessed using the mixed-meal tolerance test in patients with LADA (n = 32),
      type 1 diabetes mellitus (n = 33) and type 2 diabetes mellitus (n = 30). All
      patients were 30 to 70 years old at disease onset. The duration of diabetes in
      all groups ranged from 6 months to 10 years. The recruitment strategy was
      predefined to include at least 10 subjects in the following 3 disease onset
      categories for each group: 6 to 18 months, 19 months to 5 years and 5 to 10
      years. RESULTS: At all time-points of the mixed-meal tolerance test, patients
      with LADA had a lower stimulated C-peptide response than the type 2 diabetes
      group and a higher response than the type 1 diabetes group. The same results were
      found when the peak or area under the C-peptide curve was measured. When the
      results were stratified by time since disease onset, a similar pattern of
      residual insulin secretory capacity was observed. CONCLUSIONS: The present study
      shows that the magnitude of stimulated insulin secretion in LADA is intermediate
      between that of type 1 and type 2 diabetes mellitus.

PMID- 25572258
TI  - Maximizing throughput in label-free microspectroscopy with hybrid Raman imaging.
AB  - Raman spectroscopy is an optical method providing sample molecular composition,
      which can be analyzed (by point measurements) or spatially mapped by Raman
      imaging. These provide different information, signal-to-noise ratios, and require
      different acquisition times. Here, we quantitatively assess Raman spectral
      features and compare the two measurement methods by multivariate analysis. We
      also propose a hybrid method: scanning the beam through the sample but optically
      binning the signal at one location on the detector. This approach generates
      significantly more useful spectral signals in terms of peak visibility and
      statistical information. Additionally, by combination with a complementary
      imaging mode such as quantitative phase microscopy, hybrid imaging allows high
      throughput and robust spectral analysis while retaining sample spatial
      information. We demonstrate the improved ability to discriminate between cell
      lines when using hybrid scanning compared to typical point mode measurements, by
      quantitatively evaluating spectra taken from two macrophage-like cell lines.
      Hybrid scanning also provides better classification capability than the full
      Raman imaging mode, while providing higher signal-to-noise signals with shorter
      acquisition times. This hybrid imaging approach is suited for various
      applications including cytometry, cancer versus noncancer detection, and label
      free discrimination of cell types or tissues.

PMID- 25572259
TI  - Noninvasive high resolving power entangled photon quantum microscope.
AB  - A noninvasive high resolving power quantum microscope would facilitate progress
      in the areas of research and development in biosciences as well as in the area of
      biomedical technology. Longer-wavelength microscopes, i.e., visible or near
      infrared, can provide noninvasive features. On the other hand, shorter
      wavelengths, i.e., in the ultraviolet, can provide better resolving power. We
      propose the development of both a noninvasive and high resolving power quantum
      microscope by using two-color entangled photon ghost imaging technology.

PMID- 25572260
TI  - ZnO-coated carbon nanotubes: inter-diffusion of carboxyl groups and enhanced
      photocurrent generation.
AB  - ZnO is a defect-governed oxide and emits light at both visible and UV regimes.
      This work employs atomic layer deposition to produce oxide particles on
      oxygenated carbon nanotubes, and the composites only show emission profiles at
      short wavelengths. The quenching of defect-related emissions at long wavelengths
      is verified, owing to carboxyl diffusion into oxygen vacancies, and doping is
      supported by ZnCO3 formation in oxide lattice. Fully coated tubes display an
      increased photocurrent and the quantum efficiency increases by 22 % relative to
      the bare nanotubes. 

PMID- 25572255
TI  - Modular and orthogonal synthesis of hybrid polymers and networks.
AB  - Biomaterials scientists strive to develop polymeric materials with distinct
      chemical make-up, complex molecular architectures, robust mechanical properties
      and defined biological functions by drawing inspirations from biological systems.
      Salient features of biological designs include (1) repetitive presentation of
      basic motifs; and (2) efficient integration of diverse building blocks. Thus, an
      appealing approach to biomaterials synthesis is to combine synthetic and natural
      building blocks in a modular fashion employing novel chemical methods. Over the
      past decade, orthogonal chemistries have become powerful enabling tools for the
      modular synthesis of advanced biomaterials. These reactions require building
      blocks with complementary functionalities, occur under mild conditions in the
      presence of biological molecules and living cells and proceed with high yield and
      exceptional selectivity. These chemistries have facilitated the construction of
      complex polymers and networks in a step-growth fashion, allowing facile
      modulation of materials properties by simple variations of the building blocks.
      In this review, we first summarize features of several types of orthogonal
      chemistries. We then discuss recent progress in the synthesis of step growth
      linear polymers, dendrimers and networks that find application in drug delivery,
      3D cell culture and tissue engineering. Overall, orthogonal reactions and
      modulular synthesis have not only minimized the steps needed for the desired
      chemical transformations but also maximized the diversity and functionality of
      the final products. The modular nature of the design, combined with the potential
      synergistic effect of the hybrid system, will likely result in novel hydrogel
      matrices with robust structures and defined functions. 

PMID- 25572261
TI  - Oral Papillomas Associated With Felis catus Papillomavirus Type 1 in 2 Domestic
      Cats.
AB  - Multiple small sessile raised lesions were detected on the ventral surface of the
      tongue in two 13-year-old domestic cats. The lesions were incidental in both
      cats. Lesions from both cats appeared histologically as well-demarcated foci of
      markedly thickened folded epithelium that formed keratin-filled shallow cuplike
      structures. Large keratinocytes that contained a swollen nucleus surrounded by a
      clear cytoplasmic halo (koilocytes) were common, suggesting a diagnosis of a
      papillomavirus-induced papillomas, and papillomavirus antigen was demonstrated by
      immunohistochemistry. The papillomas exhibited diffuse intense cytoplasmic and
      nuclear immunoreactivity against cyclin-dependent kinase inhibitor 2A protein
      (also known as p16 or INK4a protein). Felis catus papillomavirus type 1 DNA
      sequences were amplified from both papillomas. The papillomas resolved in 1 cat
      within 3 months of diagnosis, while the papillomas were still visible 4 months
      after diagnosis in the other cat. This is the first evidence that these
      papillomas are caused by F. catus papillomavirus type 1. 

PMID- 25572262
TI  - Bilateral Dentate Gyrus Structural Alterations in a Cat Associated With
      Hippocampal Sclerosis and Intraventricular Meningioma.
AB  - A 13-year-old cat had a history of seizures for 3 years that resembled temporal
      lobe epilepsy. Histologic examination of the brain revealed bilateral hippocampal
      alterations, including hypergyration and broadening of the dentate gyrus
      associated with hippocampal sclerosis and an intraventricular meningioma near the
      hippocampal region. The findings in the dentate gyrus were interpreted as a
      congenital malformation; however, it could not be ruled out that the alterations
      were induced by the seizures. Similar changes of the dentate gyrus have not been
      previously described in cats. 

PMID- 25572263
TI  - Neuropathology of Natural Cytauxzoon felis Infection in Domestic Cats.
AB  - Cytauxzoonosis is a tick-borne disease of felids caused by the protozoan
      Cytauxzoon felis. This article characterizes the neuropathologic changes in 8
      cases of natural C. felis infection in domestic cats with typical clinical signs
      and pathologic changes in multiple organs. Histologic changes in the brain
      included intravascular schizont-laden macrophages in leptomeningeal and
      parenchymal arterioles and venules. Small capillaries throughout the gray and
      white matter and choroid plexus also appeared occluded. Affected vessels were
      often surrounded by small to moderate numbers of lymphocytes and plasma cells and
      multiple areas of hemorrhage. Vasculitis and fibrin thrombi were occasionally
      present. Parenchymal changes consisted of variable degrees of vacuolation of the
      gray and white matter, with microgliosis, astrocytosis, astrogliosis, and
      multiple microhemorrhages. Multiple well-demarcated areas of necrosis observed in
      4 cases were characterized by marked vacuolation of the gray or white matter,
      with necrotic neurons containing shrunken hypereosinophilic cytoplasm and
      pyknotic nuclei, nuclear debris, swollen axons, and scattered foamy macrophages.
      The changes in the brains of affected cats were attributed to vascular occlusion
      and secondary ischemia caused by the protozoal infection. 

PMID- 25572264
TI  - Melanotic oncocytic metaplasia of the nasopharynx.
AB  - We present three cases of melanotic oncocytic metaplasia of the nasopharynx. Case
      1 and Case 2 were a 70- and a 61-year-old woman, and Case 3 was a 74-year-old
      man. Although Case 1 was asymptomatic, Cases 2 and 3 had hoarseness. All cases
      were Japanese and their nasopharyngeal examination revealed single or multiple
      black nodules measuring a few millimeters in diameter. In each case, biopsies
      were performed to rule out malignancy. Histological examination showed
      respiratory mucosa with oncocytic metaplasia and melanin pigments.
      Immunohistochemically, S-100 protein and melan-A positive dendritic melanocytes
      were observed in the basal layer of the oncocytes. Melanotic oncocytic metaplasia
      is extremely rare, and so far only 21 cases have been reported in the English
      literature to our knowledge. It has been reported in only older Asians,
      predominantly in males; there have been only three female patients including our
      two cases. All of our cases were long-time smokers, which supports the previously
      described hypothesis that smoking may be a predisposing factor for melanin
      pigmentation. Since melanotic oncocytic metaplasia may clinically mimic a
      malignant tumor, it is important to be aware of this lesion. 

PMID- 25572265
TI  - BBT improves glucose homeostasis by ameliorating beta-cell dysfunction in type 2
      diabetic mice.
AB  - Impaired glucose-stimulated insulin secretion (GSIS) and increasing beta-cell
      death are two typical dysfunctions of pancreatic beta-cells in individuals that
      are destined to develop type 2 diabetes, and improvement of beta-cell function
      through GSIS enhancement and/or inhibition of beta-cell death is a promising
      strategy for anti-diabetic therapy. In this study, we discovered that the small
      molecule, N-(2-benzoylphenyl)-5-bromo-2-thiophenecarboxamide (BBT), was effective
      in both potentiating GSIS and protecting beta-cells from cytokine- or
      streptozotocin (STZ)-induced cell death. Results of further studies revealed that
      cAMP/PKA and long-lasting (L-type) voltage-dependent Ca(2) (+) channel/CaMK2
      pathways were involved in the action of BBT against GSIS, and that the cAMP/PKA
      pathway was essential for the protective action of BBT on beta-cells. An assay
      using the model of type 2 diabetic mice induced by high-fat diet combined with
      STZ (STZ/HFD) demonstrated that BBT administration efficiently restored beta-cell
      functions as indicated by the increased plasma insulin level and decrease in the
      beta-cell loss induced by STZ/HFD. Moreover, the results indicated that BBT
      treatment decreased fasting blood glucose and HbA1c and improved oral glucose
      tolerance further highlighting the potential of BBT in anti-hyperglycemia
      research. 

PMID- 25572267
TI  - Pesticide pollution of multiple drinking water sources in the Mekong Delta,
      Vietnam: evidence from two provinces.
AB  - Pollution of drinking water sources with agrochemicals is often a major threat to
      human and ecosystem health in some river deltas, where agricultural production
      must meet the requirements of national food security or export aspirations. This
      study was performed to survey the use of different drinking water sources and
      their pollution with pesticides in order to inform on potential exposure sources
      to pesticides in rural areas of the Mekong River delta, Vietnam. The field work
      comprised both household surveys and monitoring of 15 frequently used pesticide
      active ingredients in different water sources used for drinking (surface water,
      groundwater, water at public pumping stations, surface water chemically treated
      at household level, harvested rainwater, and bottled water). Our research also
      considered the surrounding land use systems as well as the cropping seasons.
      Improper pesticide storage and waste disposal as well as inadequate personal
      protection during pesticide handling and application were widespread amongst the
      interviewed households, with little overall risk awareness for human and
      environmental health. The results show that despite the local differences in the
      amount and frequency of pesticides applied, pesticide pollution was ubiquitous.
      Isoprothiolane (max. concentration 8.49 MUg L(-1)), fenobucarb (max. 2.32 MUg L(
      1)), and fipronil (max. 0.41 MUg L(-1)) were detected in almost all analyzed
      water samples (98 % of all surface samples contained isoprothiolane, for
      instance). Other pesticides quantified comprised butachlor, pretilachlor,
      propiconazole, hexaconazole, difenoconazole, cypermethrin, fenoxapro-p-ethyl,
      tebuconazole, trifloxystrobin, azoxystrobin, quinalphos, and thiamethoxam. Among
      the studied water sources, concentrations were highest in canal waters. Pesticide
      concentrations varied with cropping season but did not diminish through the year.
      Even in harvested rainwater or purchased bottled water, up to 12 different
      pesticides were detected at concentrations exceeding the European Commission's
      parametric guideline values for individual or total pesticides in drinking water
      (0.1 and 0.5 MUg L(-1); respectively). The highest total pesticide concentration
      quantified in bottled water samples was 1.38 MUg L(-1). Overall, we failed to
      identify a clean water source in the Mekong Delta with respect to pesticide
      pollution. It is therefore urgent to understand further and address drinking
      water-related health risk issues in the region.

PMID- 25572266
TI  - Subacute toxicity of titanium dioxide (TiO2) nanoparticles in male rats:
      emotional behavior and pathophysiological examination.
AB  - Titanium dioxide nanoparticles (TiO2 NPs) have a wide range of applications in
      many fields (paint, industry, medicine, additives in food colorants, and
      nutritional products). Over the past decade research, TiO2 NPs have been focused
      on the potential toxic effects of these useful materials. In the present study,
      we investigated the effects of subacute exposure to TiO2 NPs on emotional
      behavior in adult Wistar rats, the biochemical parameters, and the histology of
      organs. Animals were injected intraperitoneally (ip) with TiO2 NPs (20 mg/kg body
      weight) every 2 days for 20 days. The elevated plus-maze test showed that
      subacute TiO2 NPs treatment increased significantly the anxious index (AI)
      compared to control group. The toxicological parameters were assessed 24 h and 14
      days after the last injection of TiO2 NPs. Subacute exposure to nanoparticles
      increased the AST/ALT enzyme ratio and LDH activity. However, the blood cell
      count remained unchanged, except the platelet count increase. Histological
      examination showed a little inflammation overall. Moreover, our results provide
      strong evidence that the TiO2 NPs can induce the liver pathological changes of
      rats. The intraperitoneal injection of TiO2 NPs increased the accumulation of
      titanium in the liver, lung, and the brain. The results suggest that TiO2 NPs
      could alter the neurobehavioral performance of adult Wistar rats and promotes
      alterations in hepatic tissues. 

PMID- 25572268
TI  - Performance of the CalTOX fate and exposure model in a case study for a dioxin
      contaminated site.
AB  - Soil with high levels of polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofurans (PCDD/Fs) is found at contaminated sites all over the world.
      Transfer of PCDD/Fs from contaminated soil to the food chain could lead to
      elevated human exposure. As a complement to available monitoring data, multimedia
      fate and exposure modeling can be applied to support risk assessment of sites
      with PCDD/F contaminated soil. In this study, we evaluated the performance of the
      CalTOX fate and exposure model for 2,3,7,8-substituted PCDD/Fs against measured
      concentrations in air, soil, grass, carrots, potatoes, milk, meat, and eggs from
      a contaminated site in northern Sweden. The calculated total toxic equivalent
      (TEQ) concentrations agree with measurements within a factor of 10 for all
      exposure media but one. Results for individual congeners demonstrated that the
      model did not always perform well at describing key processes that mobilize
      PCDD/Fs out of soils, such as transfer into root crops and ingestion of soil by
      chickens. Uncertainty in only a small subset of input parameters affects the
      model output. Improved information and models describing transfer of soil
      particles onto leafy vegetation by rain splash and biotransfer factors for
      PCDD/Fs to milk, meat, and eggs are particular research needs to reduce
      uncertainties in model-based assessments. 

PMID- 25572269
TI  - Formation and potential mechanisms of polychlorinated dibenzo-p-dioxins and
      dibenzofurans on fly ash from a secondary copper smelting process.
AB  - Secondary copper smelting (SeCu) is widely considered to be an important source
      of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs;
      PCDD/Fs). Laboratory experiments were performed using SeCu fly ash as a matrix
      for thermochemical reactions to investigate the effects of fly ash on the
      formation of PCDD/Fs and the potential mechanisms. Thermochemical reactions on
      SeCu fly ash over a temperature range of 250-450  degrees C and reaction times of
      10-120 min caused the PCDD/F concentrations in the fly ash to increase
      significantly. The PCDD/F concentrations formed in the thermal reactions were
      about 99-139 times higher than the PCDD/F concentrations in the original fly ash,
      clearly indicating that fly ash promoted the formation of PCDD/Fs. The PCDFs
      dominated the PCDDs, and the PCDF/PCDD concentration ratio was about 30-40.
      Octachlorodibenzofuran (OCDF), octachlorodibenzo-p-dioxin, and the
      heptachlorodibenzofurans were the most dominant homologs that were formed. A
      comparison of the PCDD/F patterns produced in the thermochemical reactions and
      the patterns in the original fly ash suggested that the chlorination of less
      chlorinated PCDFs might be an important pathway in the formation of higher
      chlorinated furans. The results of this study indicated that SeCu fly ash has a
      high PCDD/F formation potential. It is crucial to have the fly ash filter at low
      temperature and that fly ash in the cooling system should be minimized. 

PMID- 25572270
TI  - A predictive method for crude oil volatile organic compounds emission from soil:
      evaporation and diffusion behavior investigation of binary gas mixtures.
AB  - Due to their mobility and toxicity, crude oil volatile organic compounds (VOCs)
      are representative components for oil pipeline contaminated sites detection.
      Therefore, contaminated location risk assessment, with airborne light detection
      and ranging (LIDAR) survey, in particular, requires ground-based determinative
      methods for oil VOCs, the interaction between oil VOCs and soil, and information
      on how they diffuse from underground into atmosphere. First, we developed a
      method for determination of crude oil VOC binary mixtures (take n-pentane and n
      hexane as examples), taking synergistic effects of VOC mixtures on
      polydimethylsiloxane (PDMS) solid-phase microextraction (SPME) fibers into
      consideration. Using this method, we further aim to extract VOCs from small
      volumes, for example, from soil pores, using a custom-made sampling device for
      nondestructive SPME fiber intrusion, and to study VOC transport through
      heterogeneous porous media. Second, specific surface Brunauer-Emmett-Teller (BET)
      analysis was conducted and used for estimation of VOC isotherm parameters in
      soil. Finally, two models were fitted for VOC emission prediction, and the
      results were compared to the experimental emission results. It was found that
      free diffusion mode worked well, and an empirical correction factor seems to be
      needed for the other model to adapt to our condition for single and binary
      systems. 

PMID- 25572271
TI  - Effects of alkyl-imidazolium ionic liquid [Omim]Cl on the functional diversity of
      soil microbial communities.
AB  - As low-temperature molten salts, ionic liquids (ILs) were considered to be
      "green" solvents and have begun to see large-scale applications in the chemical
      reactions, in separation processes, in electrochemistry studies, etc. In recent
      years, the toxicity of ILs has started to draw attention. To evaluate the effects
      of the ionic liquid [Omim]Cl on indigenous microbial community in soil, Biolog
      ECO plate method were used with the addition of four different concentrations of
      [Omim]Cl after four different incubation periods (7, 14, 21, 28 days). The
      present results showed that the average well color development (AWCD) was
      strongly activated when the soil was contaminated with [Omim]Cl in the early
      stages of the incubation. However, the activation effect disappeared with
      extended incubation time. Therefore, the toxic effects of the alkyl-imidazolium
      ionic liquid ([Omim]Cl) on the functional diversity of soil microbial communities
      may be reversible. In addition, the kinetic characteristics of microorganisms
      that used different categories of carbon sources indicated that phenolic
      compounds were the main C source in the sample soil.

PMID- 25572273
TI  - Predictors of hyperkalemia risk after hypertension control with aldosterone
      blockade according to the presence or absence of chronic kidney disease.
AB  - BACKGROUND/AIMS: Aldosterone antagonists have been proven to be efficient in the
      management of hypertension and the reduction of proteinuria; however, they are
      not widely used because of the risk of hyperkalemia. We assessed the predictors
      of hyperkalemia risk following hypertension control using aldosterone blockade in
      the presence or absence of chronic kidney disease (CKD). METHODS: A total of
      6,575 patients with hypertension treated between January 1, 2000, and November
      30, 2012, were evaluated for the safety of an aldosterone-blocking agent
      (spironolactone) added to preexisting blood pressure-lowering regimens.
      Hyperkalemia was defined as a serum potassium level >=5.0 mEq/l. All patients
      used 3 mechanistically complementary antihypertensive agents, including a
      diuretic and a RAAS blocker. Patients were evaluated after 4 and 8 weeks of
      treatment. The incidence of hyperkalemia, significant renal dysfunction [a
      reduction of the estimated glomerular filtration rate (eGFR) >=30%], and adverse
      effects was assessed. RESULTS: The incidence of hyperkalemia in the presence or
      absence of CKD was 50.4 and 42.6% after 4 weeks (p = 0.001) and 3.8 and 3.0%
      after 8 weeks, respectively (p = 0.371). A logistic regression analysis revealed
      that medication, CKD, basal hyperkalemia, reduction in eGFR, and diabetes were
      all predictive of a hyperkalemia risk following spironolactone use. CONCLUSION:
      Spironolactone was well tolerated by selected CKD patients. The risk of serious
      hyperkalemia or a significant reduction of eGFR appears to be low. Strict
      monitoring over the first month of treatment followed by standard surveillance
      for angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers
      is suggested.

PMID- 25572272
TI  - Short-term effects of multiple ozone metrics on daily mortality in a megacity of
      China.
AB  - Epidemiological studies have widely demonstrated association between ambient
      ozone and mortality, though controversy remains, and most of them only use a
      certain metric to assess ozone levels. However, in China, few studies have
      investigated the acute effects of ambient ozone, and rare studies have compared
      health effects of multiple daily metrics of ozone. The present analysis aimed to
      explore variability of estimated health effects by using multiple temporal ozone
      metrics. Six metrics of ozone, 1-h maximum, maximum 8-h average, 24-h average,
      daytime average, nighttime average, and commute average, were used in a time
      series study to investigate acute mortality associated with ambient ozone
      pollution in Guangzhou, China, using 3 years of daily data (2006-2008). We used
      generalized linear models with Poisson regression incorporating natural spline
      functions to analyze the mortality, ozone, and covariate data. We also examined
      the association by season. Daily 1- and 8-h maximum, 24-h average, and daytime
      average concentrations yielded statistically significant associations with
      mortality. An interquartile range (IQR) of O3 metric increase of each ozone
      metric (lag 2) corresponds to 2.92 % (95 % confidence interval (CI) 0.24 to
      5.66), 3.60 % (95 % CI, 0.92 to 8.49), 3.03 % (95 % CI, 0.57 to 15.8), and 3.31 %
      (95 % CI, 0.69 to 10.4) increase in daily non-accidental mortality, respectively.
      Nighttime and commute metrics were weakly associated with increased mortality
      rate. The associations between ozone and mortality appeared to be more evident
      during cool season than in the warm season. Results were robust to adjustment for
      co-pollutants, weather, and time trend. In conclusion, these results indicated
      that ozone, as a widespread pollutant, adversely affects mortality in Guangzhou. 

PMID- 25572274
TI  - Near-medians that avoid the corners; a combinatorial probability approach.
AB  - BACKGROUND: The breakpoint median for a set of k >= 3 random genomes tends to
      approach (any) one of these genomes ("corners") as genome length increases,
      although there are diminishing proportion of medians equidistant from all k
      ("medians in the middle"). Algorithms are likely to miss the latter, and this has
      consequences for the general case where input genomes share some or many gene
      adjacencies, where the tendency for the median to be closer to one input genome
      may be an artifact of the corner tendency. RESULTS: We present a simple sampling
      procedure for constructing a "near median" that represents a compromise among k
      random genomes and that has only a slightly greater breakpoint distance to all of
      them than the median does. We generalize to the realistic case where genomes
      share varying proportions of gene adjacencies. We present a supplementary
      sampling scheme that brings the constructed genome even closer to median status.
      CONCLUSIONS: Our approach is of particular use in the phylogenetic context where
      medians are repeatedly calculated at ancestral nodes, and where the corner effect
      prevents different parts of the phylogeny from communicating with each other.

PMID- 25572275
TI  - Lupus pernio with 2 years of preceding symptomatic gastric sarcoidosis.

PMID- 25572276
TI  - Risk factors for postoperative intra-abdominal septic complications after surgery
      in Crohn's disease: A meta-analysis of observational studies.
AB  - BACKGROUND AND AIMS: Postoperative intra-abdominal septic complications [IASCs]
      are the most feared risks of surgery for Crohn's disease[CD]. The risk factors
      for IASCs still remain controversial. The aim of this study was to assess the
      risk factors for IASCs in CD patients undergoing abdominal surgery. METHODS:
      MEDLINE, Cochrane Library, and EMBASE were searched to identify observational
      studies reporting the risk factors for IASCs in CD patients. A meta-analysis was
      conducted to investigate the impact of various risk factors on IASCs in CD. The
      GRADE [Grading of Recommendations Assessment, Development and Evaluation]
      approach was used for quality assessment of evidence on outcome levels. RESULTS:
      This review included 15 studies evaluating 3807 patients undergoing 4189
      operations. The meta-analyses found that low albumin levels (odds ratio [OR]:
      1.93; 95% confidence interval [CI]: 1.362.75), preoperative steroids use [OR:
      1.99; 95% CI: 1.54-2.57], a preoperative abscess [OR: 1.94; 95% CI: 1.263.0],
      previous surgery history [OR: 1.50; 95% CI: 1.151.97] may be risk factors for
      IASCs. There were no associations between anastomosis methods [OR: 0.94; 95% CI:
      0.58-1.53], biologics therapy [OR: 1.29; 95% CI: 0.792.11], and immunomodulator
      use [OR: 1.07; 95% CI: 0.661.73] with the risk of IASCs. Due to observational
      design, the quality of evidence was regarded low or moderate for these risk
      factors by the GRADE approach. CONCLUSIONS: This meta-analysis provides some
      evidence that steroids use, previous surgical history, a preoperative abscess,
      and low albumin levels may be associated with higher rates of IASCs in CD.
      Knowledge about those risk factors may influence treatment and procedure-related
      decisions, and possibly reduce the ss rate.

PMID- 25572277
TI  - Optimising the cutoffs of cognitive screening instruments in pragmatic diagnostic
      accuracy studies: maximising accuracy or the Youden index?
AB  - BACKGROUND/AIMS: The optimal method of establishing test cutoffs or cutpoints for
      cognitive screening instruments (CSIs) is uncertain. Of the available methods,
      two base cutoffs on either the maximal test accuracy or the maximal Youden index.
      The aim of this study was to compare the effects of using these alternative
      methods of establishing cutoffs. METHODS: Datasets from three pragmatic
      diagnostic accuracy studies which examined the Mini-Mental State Examination
      (MMSE), the Addenbrooke's Cognitive Examination-Revised (ACE-R), the Montreal
      Cognitive Assessment (MoCA), and the Test Your Memory (TYM) test were analysed to
      calculate test sensitivity and specificity using cutoffs based on either maximal
      test accuracy or the maximal Youden index. RESULTS: For ACE-R, MoCA, and TYM,
      optimal cutoffs for dementia diagnosis differed from those in index studies when
      defined using either the maximal accuracy or the maximal Youden index method.
      Optimal cutoffs were higher for MMSE, MoCA, and TYM when using the maximal Youden
      index method and consequently more sensitive. CONCLUSION: Revision of the cutoffs
      for CSIs established in index studies may be required to optimise performance in
      pragmatic diagnostic test accuracy studies which more closely resemble clinical
      practice.

PMID- 25572278
TI  - Gene order alignment on trees with multiOrthoAlign.
AB  - We relate the comparison of gene orders to an alignment problem. Our evolutionary
      model accounts for both rearrangement and content-modifying events. We present a
      heuristic based on dynamic programming for the inference of the median of three
      genomes and apply it in a phylogenetic framework. multiOrthoAlign is shown
      accurate on simulated and real datasets, and shown to significantly improve the
      running-time of DupLoCut, an "almost" exact algorithm based on linear
      programming, developed recently for the same problem. 

PMID- 25572279
TI  - Decreased low back pain intensity and differential gene expression following
      Calmare(r): results from a double-blinded randomized sham-controlled study.
AB  - In this double-blinded, randomized controlled trial we evaluated the effects of
      Calmare(r), a non-invasive neurocutaneous electrical pain intervention, on lower
      back pain intensity as measured by the "worst" pain score and on pain
      interference using the Brief Pain Inventory-Short Form, on measures of pain
      sensitivity assessed by quantitative sensory testing, and on mRNA expression of
      pain sensitivity genes. Thirty participants were randomized to receive up to 10
      sessions of Calmare(r) treatment (n = 15) or a sham treatment (n = 15) using the
      same device at a non-therapeutic threshold. At 3 weeks after conclusion of
      treatment, compared with the sham group, the Calmare(r) group reported a
      significant decrease in the "worst" pain and interference scores. There were also
      significant differences in pain sensitivity and differential mRNA expression of
      17 pain genes, suggesting that Calmare(r) can be effective in reducing pain
      intensity and interference in individuals with persistent low back pain by
      altering the mechanisms of enhanced pain sensitivity. Further study of long-term
      pain outcomes, particularly functional status, analgesic use and health care
      utilization, is warranted.

PMID- 25572280
TI  - Towards ratiometric sensing of amyloid fibrils in vitro.
AB  - The aggregation of amyloid-beta peptide and its accumulation in the human brain
      has an important role in the etiology of Alzheimer's disease. Thioflavin T has
      been widely used as a fluorescent marker for these amyloid aggregates.
      Nevertheless, its complex photophysical behavior, with strong wavelength
      dependencies of all its fluorescence properties, requires searching for new
      fluorescent probes. The use of 2-(2'-hydroxyphenyl)imidazo[4,5-b]pyridine (HPIP),
      which shows two emission bands and a rich excited-state behavior due to the
      existence of excited-state intramolecular processes of proton transfer and charge
      transfer, is proposed. These properties result in a high sensitivity of HPIP
      fluorescence to its microenvironment and cause a large differential fluorescence
      enhancement of the two bands upon binding to aggregates of the amyloid-beta
      peptide. Based on this behavior, a very sensitive ratiometric method is
      established for the detection and quantification of amyloid fibrils, which can be
      combined with the monitoring of fluorescence anisotropy. The binding selectivity
      of HPIP is discussed on the basis of the apparent binding equilibrium constants
      of this probe to amyloid-beta (1-42) fibrils and to the nonfibrillar protein
      bovine serum albumin. Finally, an exhaustive comparison between HPIP and
      thioflavin T is presented to discuss the sensitivity and specificity of these
      probes to amyloid aggregates and the significant advantages of the HPIP dye for
      quantitative determinations. 

PMID- 25572281
TI  - RAG1-mediated ubiquitylation of histone H3 is required for chromosomal V(D)J
      recombination.
AB  - RAG1 and RAG2 proteins are key components in V(D)J recombination. The core region
      of RAG1 is capable of catalyzing the recombination reaction; however, the
      biological function of non-core RAG1 remains largely unknown. Here, we show that
      in a murine-model carrying the RAG1 ring-finger conserved cysteine residue
      mutation (C325Y), V(D)J recombination was abrogated at the cleavage step, and
      this effect was accompanied by decreased mono-ubiquitylation of histone H3.
      Further analyses suggest that un-ubiquitylated histone H3 restrains RAG1 to the
      chromatin by interacting with the N-terminal 218 amino acids of RAG1. Our data
      provide evidence for a model in which ubiquitylation of histone H3 mediated by
      the ring-finger domain of RAG1 triggers the release of RAG1, thus allowing its
      transition into the cleavage phase. Collectively, our findings reveal that the
      non-core region of RAG1 facilitates chromosomal V(D)J recombination in a
      ubiquitylation-dependent pathway. 

PMID- 25572282
TI  - Population-based study of QT interval prolongation in patients with rheumatoid
      arthritis.
AB  - OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of
      cardiovascular morbidity and mortality. Heart rate corrected QT interval (QTc)
      (which is obtained from a 12-lead electrocardiogram (ECG) and reflects
      ventricular repolarisation duration) is a strong predictor of cardiovascular
      mortality. Our primary purpose is to determine the impact of QTc prolongation on
      mortality in RA patients. METHODS: A population-based inception cohort of
      patients with RA fulfilling the 1987 ACR criteria in 1988-2007 was identified,
      with an age- and sex-matched comparison cohort and followed until death,
      migration or until the end of 2008. Data were collected on ECG variables,
      medications known to prolong QT interval, electrolytes, cardiovascular risk
      factors and disease status and RA disease characteristics. Cox proportional
      hazards models were used to examine QTc prolongation as predictor of mortality.
      RESULTS: QTc prolongation prior to RA incidence/index date was similar in RA
      (15%) and non-RA (18%) subjects. During follow-up, the cumulative incidence of
      QTc prolongation was higher among RA (48% at 20 years after RA incidence) than
      non-RA (38% at 20 years after index date; p=0.004). Idiopathic QTc prolongation
      (excluding prolongations explained by ECG changes, medications, etc.) was
      marginally associated with all-cause mortality (HR: 1.28; 95% CI: 0.91-1.81,
      p=0.16), but was not associated with cardiovascular mortality (HR: 1.10; 95%
      CI:0.43-2.86, p=0.83) in RA. CONCLUSIONS: RA patients have a significantly
      elevated risk of developing QTc prolongation. However, idiopathic prolonged QTc
      was only marginally associated with all-cause mortality in RA patients. The
      clinical implications of these findings in RA require further study.

PMID- 25572284
TI  - Groundwater drift as a tracer for identifying sources of spring discharge.
AB  - Groundwater invertebrate drift, collected from the spring outlets at the
      interface of vadose and phreatic zones, has been examined for its potential for
      identifying sources of discharge from a karst aquifer. Concurrently, major ion
      geochemistry, dissolved inorganic carbon (delta13CDIC), particulate organic
      carbon (delta13CPOC), and naturally occurring stable isotopes of oxygen and
      tritium (delta18O, 3H) were investigated over a period of 1 year in two outlets,
      a temporary (TS) and a perennial (PS) spring. A few differences in major ion
      geochemistry and stable isotope composition were found between the two springs
      together with moderate seasonal variability. In contrast, invertebrate drift
      showed clear differences between TS and PS springs in density and composition.
      Canonical correspondence analysis showed the presence of two distinct groups of
      samples from TS and PS, with Ca2+ as the only significant explanatory variable
      for differences in drift composition. Finally, certain species from the drift
      were found to be useful tracers for distinguishing between the phreatic and the
      epikarst and vadose zones as the origin of spring water.

PMID- 25572283
TI  - Combination of HSV1-TK/shTERT by retrovirus vector inhibits hepatocellular
      carcinoma cell growth in vitro and in vivo.
AB  - Hepatocellular carcinoma (HCC) is a common malignant carcinoma worldwide and the
      third leading cause of cancer mortality. However, current treatment strategies
      are not potent enough to combat this disease. Therefore, identification of novel
      and more effective treatments is crucial. Of the current methods, gene therapy,
      which targets cancer-specific expression and limits toxicity, is a new strategy
      for treating cancers. In this study, we developed a retroviral vector containing
      herpes simplex virus type-1-thymidine kinase (HSV1-TK) and a short hairpin RNA
      for the human telomerase reverse transcriptase (hTERT) gene and investigated the
      antitumor effects in an in vitro and in vivo mouse model of liver cancer,
      monitored by PET image. In vitro experiments on HCC cells in the TK-shTERT
      treatment group showed significant accumulation of 18F-FHBG, which preferentially
      inhibits HCC cell growth with extremely limited toxicity in normal cells. In vivo
      studies showed a significant reduction of growth in the TK-shTERT treatment
      group. In conclusion, these findings showed that combination HSV1-TK/hTERT gene
      therapy effectively and safely inhibits HCC cell growth in vitro and in vivo and
      is worthy of development in clinical trials for the treatment of HCC.

PMID- 25572286
TI  - Receptor activator of nuclear factor-kappaB ligand (RANKL)/RANK/osteoprotegerin
      system in bone and other tissues (review).
AB  - The receptor activator of nuclear factor-kappaB ligand
      (RANKL)/RANK/osteoprotegerin (OPG) system was identified in the late 1990s,
      ending the search for the specific factors expressed by osteoblasts and stromal
      cells in order to regulate osteoclastogenesis. The identification of the
      RANKL/RANK/OPG system was a breakthrough in bone biology; however, the system not
      only works as a dominant mediator in osteoclast activation, formation and
      survival, but also functions in other tissues, including the mammary glands,
      brain and lymph nodes. Evidence has indicated that the existence of the
      RANKL/RANK/OPG system in these tissues suggests that it may have specific
      functions beyond those in bone. Disorders of the RANKL/RANK/OPG system are
      associated with certain human diseases, including postmenopausal osteoporosis,
      rheumatoid arthritis (RA), bone tumors and certain bone metastatic tumors.
      Genetic studies have indicated that the RANKL/RANK/OPG system may be a key
      regulator in the formation of lymph nodes and in the autoimmune disease RA, which
      further suggests that the immune system may interact with the RANKL/RANK/OPG
      system. The present review aimed to provide an overview of the role of the
      RANKL/RANK/OPG system in osteoclastogenesis, bone disease and tissues beyond
      bone.

PMID- 25572285
TI  - Saturation mutagenesis of TsrA Ala4 unveils a highly mutable residue of
      thiostrepton A.
AB  - Thiopeptides are post-translationally processed macrocyclic peptide metabolites,
      characterized by extensive backbone and side chain modifications that include a
      six-membered nitrogeneous ring, thiazol(in)e/oxazol(in)e rings, and dehydrated
      amino acid residues. Thiostrepton A, one of the more structurally complex and
      well-studied thiopeptides, contains a second macrocycle bearing a quinaldic acid
      moiety. Antibacterial, antimalarial, and anticancer properties have been
      described for thiostrepton A and other thiopeptides, although the molecular
      details for binding the cellular target in each case are not fully elaborated. We
      previously demonstrated that a mutation of the TsrA core peptide, Ala4Gly,
      supported the successful production of the corresponding thiostrepton variant. To
      more thoroughly probe the thiostrepton biosynthetic machinery's tolerance toward
      structural variation at the fourth position of the TsrA core peptide, we report
      here the saturation mutagenesis of this residue using a fosmid-dependent
      biosynthetic engineering method and the isolation of 16 thiostrepton analogues.
      Several types of side chain substitutions at the fourth position of TsrA,
      including those that introduce polar or branched hydrophobic residues are
      accepted, albeit with varied preferences. In contrast, proline and amino acid
      residues inherently charged at physiological pH are not well-tolerated at the
      queried site by the thiostrepton biosynthetic system. These newly generated
      thiostrepton analogues were assessed for their antibacterial activities and
      abilities to inhibit the proteolytic functions of the eukaryotic 20S proteasome.
      We demonstrate that the identity of the fourth amino acid residue in the
      thiostrepton scaffold is not critical for either ribosome or proteasome
      inhibition. 

PMID- 25572287
TI  - The tryptophan derivative, tranilast, and conditioned medium with indoleamine 2,3
      dioxygenase-expressing cells inhibit the proliferation of lymphoid malignancies.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an enzyme that catalyzes tryptophan
      degradation and induces immunosuppression. Although IDO is an important factor
      that allows tumors to escape from immunological attack, its effect on lymphoid
      malignancies has not been fully revealed. We evaluated the expression of IDO in
      samples from patients with B-cell malignancies. The IDO expression in the tumor
      samples was comparable to those in peripheral blood mononuclear cells from
      healthy donors and had mainly originated from non-B cell populations. We
      introduced IDO gene into Chinese hamster ovary (CHO) cells. We then cultured
      various cell lines using CHO- or CHO-IDO-conditioned medium. Compared with the
      CHO medium (CHO-CM), the CHO-IDO medium (IDO-CM) decreased the viability of
      lymphoid cell lines but not those of the non-lymphoid lines. Next, we examined
      the effects of tryptophan metabolites on lymphoid tumors, and revealed that the
      drug N-[3',4'-dimethoxycinnamoyl] anthranilic acid (tranilast), a synthetic
      derivative of the tryptophan metabolite, was able to repress proliferation and
      dose-dependently induce cell death of lymphoid cell lines. Tranilast induced the
      activation of the c-Jun N-terminal kinase, which is activated by cellular stress,
      in lymphoid cells. The effect of tranilast on lymphoid cells was independent of
      the aryl hydrocarbon receptor (AhR) although tranilast has been reported to be an
      AhR agonist. Finally, the administration of tranilast decreased murine lymphoid
      tumor progression in vivo. These results indicated that IDO and tryptophan
      derivatives, particularly tranilast, can be tools for the therapy for lymphoid
      malignancies.

PMID- 25572288
TI  - Enhancing the Performance of a robust sol-gel-processed p-type delafossite CuFeO2
      photocathode for solar water reduction.
AB  - Delafossite CuFeO2 is a promising material for solar hydrogen production, but is
      limited by poor photocurrent. Strategies are demonstrated herein to improve the
      performance of CuFeO2 electrodes prepared directly on transparent conductive
      substrates by using a simple sol-gel technique. Optimizing the delafossite layer
      thickness and increasing the majority carrier concentration (through the thermal
      intercalation of oxygen) give insights into the limitations of photogenerated
      charge extraction and enable performance improvements. In oxygen-saturated
      electrolyte, (sacrificial) photocurrents (1 sun illumination) up to 1.51 mA cm(
      2) at +0.35 V versus a reversible hydrogen electrode (RHE) are observed. Water
      photoreduction with bare delafossite is limited by poor hydrogen evolution
      catalysis, but employing methyl viologen as an electron acceptor verifies that
      photogenerated electrons can be extracted from the conduction band before
      recombination into mid-gap trap states identified by electrochemical impedance
      spectroscopy. Through the use of suitable oxide overlayers and a platinum
      catalyst, sustained solar hydrogen production photocurrents of 0.4 mA cm(-2) at 0
      V versus RHE (0.8 mA cm(-2) at -0.2 V) are demonstrated. Importantly, bare CuFeO2
      is highly stable at potentials at which photocurrent is generated. No degradation
      is observed after 40 h under operating conditions in oxygen-saturated
      electrolyte. 

PMID- 25572289
TI  - A zebrafish model for subgenomic hepatitis C virus replication.
AB  - Persistent infection with hepatitis C virus (HCV) is a major risk factor in the
      development of hepatocellular carcinoma. The elucidation of the pathogenesis of
      HCV-associated liver disease is hampered by the absence of an appropriate small
      animal model. Zebrafish exhibits high genetic homology to mammals, and is easily
      manipulated experimentally. In this study, we describe the use of a zebrafish
      model for the analysis of HCV replication mechanisms. As the 5' untranslated
      region (UTR), the core protein, the non-structural protein 5B (NS5B) and the
      3'UTR are essential for HCV replication, we constructed a HCV sub-replicon gene
      construct including the 4 gene sequences and the enhanced green fluorescent
      protein (EGFP) reporter gene; these genes were transcribed through the mouse
      hepatocyte nuclear factor 4 (mHNF4) promoter. By microinjection of the subgenomic
      replicon vector into zebrafish larvae, the virus was easily detected by observing
      EGFP fluorescence in the liver. The positive core and NS5B signals showed
      positive expression of the HCV gene construct in zebrafish by reverse
      transcription-polymerase chain reaction (RT-PCR) and western blot analysis.
      Importantly, the negative strand sequence of the HCV subgenomic RNA was detected
      by RT-PCR and hybridization in situ, demonstrating that the HCV sub-replicon has
      positive replication activity. Furthermore, the hybridization signal mainly
      appeared in the liver region of larvae, as detected by the sense probe of the
      core protein or NS5B, which confirmed that the sub-replicon amplification
      occurred in the zebrafish liver. The amplification of the sub-replicon caused
      alterations in the expression of certain genes, which is similar to HCV infection
      in human liver cells. To verify the use of this zebrafish model in drug
      evaluation, two drugs against HCV used in clinical practice, ribavirin and
      oxymatrine, were tested and these drugs showed significant inhibition of
      replication of the HCV sub-replicon in the larvae. In conclusion, this zebrafish
      model of HCV may prove to be a novel and simple in vivo model for the study of
      the mechanisms of HCV replication and may also prove useful in the disovery of
      new anti-HCV drugs.

PMID- 25572291
TI  - Individual Behavioral Response Mediates Endocrine Changes Induced by Social
      Interactiona.

PMID- 25572290
TI  - Molecularly imprinted polymer decorated nanoporous gold for highly selective and
      sensitive electrochemical sensors.
AB  - Electrochemical nanosensors based on nanoporous gold leaf (NPGL) and molecularly
      imprinted polymer (MIP) are developed for pharmaceutical analysis by using
      metronidazole (MNZ) as a model analyte. NPGL, serving as the loading platform for
      MIP immobilization, possesses large accessible surface area with superb electric
      conductivity, while electrochemically synthesized MIP thin layer affords
      selectivity for specific recognition of MNZ molecules. For MNZ determination, the
      hybrid electrode shows two dynamic linear range of 5 * 10(-11) to 1 * 10(-9) mol
      L(-1) and 1 * 10(-9) to 1.4 * 10(-6) mol L(-1) with a remarkably low detection
      limit of 1.8 * 10(-11) mol L(-1) (S/N = 3). In addition, the sensor exhibits high
      binding affinity and selectivity towards MNZ with excellent reproducibility and
      stability. Finally, the reliability of MIP-NPGL for MNZ detection is proved in
      real fish tissue samples, demonstrating the potential for the proposed
      electrochemical sensors in monitoring drug and biological samples.

PMID- 25572292
TI  - The secret life of a megakaryocyte: emerging roles in bone marrow homeostasis
      control.
AB  - Megakaryocytes are rare cells found in the bone marrow, responsible for the
      everyday production and release of millions of platelets into the bloodstream.
      Since the discovery and cloning, in 1994, of their principal humoral factor,
      thrombopoietin, and its receptor c-Mpl, many efforts have been directed to define
      the mechanisms underlying an efficient platelet production. However, more
      recently different studies have pointed out new roles for megakaryocytes as
      regulators of bone marrow homeostasis and physiology. In this review we discuss
      the interaction and the reciprocal regulation of megakaryocytes with the
      different cellular and extracellular components of the bone marrow environment.
      Finally, we provide evidence that these processes may concur to the
      reconstitution of the bone marrow environment after injury and their deregulation
      may lead to the development of a series of inherited or acquired pathologies. 

PMID- 25572293
TI  - Stem cell activation in skeletal muscle regeneration.
AB  - Muscle stem cell (satellite cell) activation post muscle injury is a transient
      and critical step in muscle regeneration. It is regulated by physiological cues,
      signaling molecules, and epigenetic regulatory factors. The mechanisms that
      coherently turn on the complex activation process shortly after trauma are just
      beginning to be illuminated. In this review, we will discuss the current
      knowledge of satellite cell activation regulation. 

PMID- 25572298
TI  - Structural diversity of new solid-state luminophores based on quinoxaline-beta
      ketoiminate boron difluoride complexes with remarkable fluorescence switching
      properties.
AB  - A series of structurally simple yet highly tunable organoboron luminophores was
      designed and synthesized. The solid-state fluorescence quantum yields exhibit
      nearly exponential growth by decorating the luminophore with additional
      sterically demanding substituents. Uniquely, the luminescence of these
      organoboron dyes can be easily switched on/off by acidic/basic vapors, yielding a
      solid-state fluorescence switching function. 

PMID- 25572295
TI  - Electron transfer and reaction mechanism of laccases.
AB  - Laccases are part of the family of multicopper oxidases (MCOs), which couple the
      oxidation of substrates to the four electron reduction of O2 to H2O. MCOs contain
      a minimum of four Cu's divided into Type 1 (T1), Type 2 (T2), and binuclear Type
      3 (T3) Cu sites that are distinguished based on unique spectroscopic features.
      Substrate oxidation occurs near the T1, and electrons are transferred
      approximately 13 A through the protein via the Cys-His pathway to the T2/T3
      trinuclear copper cluster (TNC), where dioxygen reduction occurs. This review
      outlines the electron transfer (ET) process in laccases, and the mechanism of O2
      reduction as elucidated through spectroscopic, kinetic, and computational data.
      Marcus theory is used to describe the relevant factors which impact ET rates
      including the driving force, reorganization energy, and electronic coupling
      matrix element. Then, the mechanism of O2 reaction is detailed with particular
      focus on the intermediates formed during the two 2e(-) reduction steps. The first
      2e(-) step forms the peroxide intermediate, followed by the second 2e(-) step to
      form the native intermediate, which has been shown to be the catalytically
      relevant fully oxidized form of the enzyme.

PMID- 25572294
TI  - Laccases of prokaryotic origin: enzymes at the interface of protein science and
      protein technology.
AB  - The ubiquitous members of the multicopper oxidase family of enzymes oxidize a
      range of aromatic substrates such as polyphenols, methoxy-substituted phenols,
      amines and inorganic compounds, concomitantly with the reduction of molecular
      dioxygen to water. This family of enzymes can be broadly divided into two
      functional classes: metalloxidases and laccases. Several prokaryotic
      metalloxidases have been described in the last decade showing a robust activity
      towards metals, such as Cu(I), Fe(II) or Mn(II) and have been implicated in the
      metal metabolism of the corresponding microorganisms. Many laccases, with a
      superior efficiency for oxidation of organic compounds when compared with metals,
      have also been identified and characterized from prokaryotes, playing roles that
      more closely conform to those of intermediary metabolism. This review aims to
      present an update of current knowledge on prokaryotic multicopper oxidases, with
      a special emphasis on laccases, anticipating their enormous potential for
      industrial and environmental applications. 

PMID- 25572299
TI  - Severe rectal complications after prostate brachytherapy.
AB  - PURPOSE: Some investigators have reported severe rectal complications after
      brachytherapy. Due to the low number of such events, their relationship to
      dosimetric parameters has not been well characterized. METHODS AND MATERIALS: A
      total of 3126 patients were treated with low dose rate brachytherapy from 1998
      through 2010. 2464 had implant alone, and 313 had implant preceded by 44-46Gy
      supplemental external beam radiation (EBRT). Post-implant dosimetry was based on
      a CT scan obtained on the day of implant, generally within 30min of the
      procedure. Every patient's record was reviewed for occurrence of rectal
      complications. RESULTS: Eight of 2464 patients (0.32%) treated with brachytherapy
      alone developed a radiation-related rectal fistula. Average prostatic and rectal
      dose parameters were moderately higher for fistula patients than for patients
      without a severe rectal complication. For instance, the average R100 was 1.2+/
      0.75cc for fistula patients, versus 0.37+/-0.88cc for non-fistula patients.
      However, the fistula patients' values were well within the range of values for
      patients without a rectal complication. Four patients had some attempt at repair
      or reconstruction, but long-term functional outcomes were not favorable.
      CONCLUSIONS: Rectal fistulas are a very uncommon potential complication of
      prostate brachytherapy, which can occur even in the setting of acceptable day 0
      rectal doses. Their occurrence is not easily explained by standard dosimetric or
      clinical factors.

PMID- 25572301
TI  - Anisotropic gold nanoassembly: a study on polarization-dependent and polarization
      selective surface-enhanced Raman scattering.
AB  - A simple one-step process was adopted to fabricate anisotropic gold
      nanoassemblies. Evaporation-assisted nanoparticle assembly at the meniscus was
      maintained in this regard. Scanning electron microscopy confirmed that the
      constituent nanoparticles of the anisotropic gold nanoassembly are neither in
      physical contact nor agglomerated; instead, they are separated by a small
      interparticle gap. Crystal violet was adsorbed on the anisotropic gold
      nanoassembly, and a large enhancement (several orders of magnitude) in surface
      enhanced Raman scattering (SERS) was observed. The assembly was thus proved to be
      highly SERS-active. Such an anisotropic gold nanoassembly allowed polarization
      dependent and polarization selective SERS experiments to be carried out.
      Inhomogeneous SERS and surface plasmon resonance distribution were observed along
      the assembly. Polarization-dependent SERS enhancement reached its highest value
      at in-plane polarization to the long axis, whereas polarization-selective SERS
      characteristics at the same spatial position showed uniform enhancement.
      Fluorescence emission accompanied with SERS signals was also characterized.
      Polarization-dependent fluorescence was enhanced at in-plane polarization to the
      long axis, whereas polarization-selective fluorescence was not enhanced. The
      experimental results were correlated and explained with three-dimensional finite
      definite time domain simulations as well. Such interstitial-limited gold
      nanoassembly provides means to realize polarized SERS characteristics for
      ensemble SERS measurements, which are important not only for the application
      oriented fabrication of SERS-active substrates but also for understanding their
      feasibility in those applications. 

PMID- 25572297
TI  - CXCL12/CXCR4 axis in the pathogenesis of acute lymphoblastic leukemia (ALL): a
      possible therapeutic target.
AB  - Acute lymphoblastic leukemia (ALL) is the commonest childhood malignancy,
      accounting for approximately 80 % of leukemia in the pediatric group, and its
      etiology is unknown. This neoplasia is characterized by male predominance, high
      risk features and poor outcome, mainly in recurrence patients and adults. In
      recent years, advances in the success of childhood ALL treatment were verified,
      and the rate of cure is over 80 % of individuals. However, there is a
      considerable scope for improving therapeutic outcome in this neoplasia.
      Improvements in ALL therapy might readily be achieved by developing additional
      biomarkers that can predict and refine prognosis in patients with ALL. In normal
      hematopoietic cells, cytokines provide the stimulus for proliferation, survival,
      self-renewal, differentiation and functional activation. Abnormalities of
      cytokines are characteristic in all forms of leukemia, including ALL. The stromal
      cell-derived factor-1 (SDF-1 or CXCL12) is a member of the CXC chemokine family
      that binds to CXC chemokine receptor 4 (CXCR4). The CXCL12/CXCR4 axis appears to
      play a role in dissemination of solid tumors and hematopoietic diseases.
      Understanding the mechanisms by which ALL cells are disseminated will provide
      additional information to expand therapeutic approach. Therefore, this review
      summarizes information relating to ALL cell biology, focusing specifically in a
      cytokine receptor important axis, CXCL12/CXCR4, that may have implications for
      novel treatment strategies to improve life expectancy of patients with this
      neoplasia. 

PMID- 25572300
TI  - Fndc5 overexpression facilitated neural differentiation of mouse embryonic stem
      cells.
AB  - Fndc5 has been recently recognized as a myokine which could be cleaved and
      secreted into blood stream. It is termed as irisin with an important role in
      thermogenesis and energy homeostasis. Increased expression of Fndc5 has been
      reported upon retinoic acid treatment during neural differentiation and its
      knockdown decreased neural differentiation and neurite outgrowth. This study
      tries to evaluate the effect of Fndc5 overexpression on rate of neural
      differentiation in mouse. (Thus, transduced cell line of mouse embryonic stem
      cell with ability to express Fndc5 under Doxycycline treatment was established.
      Subsequently, the effect of overexpression of Fndc5 on different stages of neural
      differentiation was studied). Our study showed an increase enhancement in
      neuronal precursor markers and mature neuron markers upon overexpression of
      Fndc5, concluding that Fndc5 facilitates neural differentiation. This effect
      might be related to increased expression of BDNF following overexpression of
      Fndc5. Our findings are consistent with recent studies reporting a similar role
      for Fndc5 in proliferation of neural cells and increase in the expression of
      neurotrophins like BDNF. 

PMID- 25572296
TI  - Autophagy and cell reprogramming.
AB  - Autophagy is an evolutionarily conserved process that degrades cytoplasmic
      components, thus contributing to cell survival and tissue homeostasis. Recent
      studies have demonstrated that autophagy maintains stem cells in relatively
      undifferentiated states (stemness) and also contributes to differentiation
      processes. Autophagy likewise plays a crucial role in somatic cell reprogramming,
      a finely regulated process that resets differentiated cells to a pluripotent
      state and that requires comprehensive alterations in transcriptional activities
      and epigenetic signatures. Autophagy assists in manifesting the functional
      consequences that arise from these alterations by modifying cellular protein
      expression profiles. The role of autophagy appears to be particularly relevant
      for early phases of cell reprogramming during the generation of induced
      pluripotent stems cells (iPSCs). In this review, we provide an overview of the
      core molecular machinery that constitutes the autophagic degradation system,
      describe the roles of autophagy in maintenance, self-renewal, and differentiation
      of stem cells, and discuss the autophagic process and its regulation during cell
      reprogramming. 

PMID- 25572302
TI  - Significance of serum neurokinin B and kisspeptin levels in the differential
      diagnosis of premature thelarche and idiopathic central precocious puberty.
AB  - The aim of the present study was to investigate the diagnostic role of serum
      neurokinin B level and its relationship with kisspeptin and leptin, which are
      known to be involved in the initiation of pubertal process. Girls who presented
      with breast development (<8 years) were included in the study. All patients
      underwent bone age assessment. Basal levels of serum follicle stimulating hormone
      and luteinizing hormone were measured and gonadotropin releasing hormone
      stimulation test was performed. Patients with a bone age/chronological age ratio
      >1 and a peak luteinizing hormone response in gonadotropin releasing hormone
      stimulation test >5mIU/L were included in the central precocious puberty group,
      while patients who did not meet these criteria were included in the premature
      thelarche group. Patients with organic pathologies were excluded. Healthy
      prepubertal girls with similar age were included as the control group. Leptin,
      kisspeptin and neurokinin B levels were measured by ELISA method. The study
      included 20 girls with idiopathic central precocious puberty 22 girls with
      premature thelarche and 24 prepubertal controls. While serum kisspeptin, leptin
      and neurokinin B levels were significantly higher in central precocious puberty
      and premature thelarche groups compared to controls, no significant difference
      was found between central precocious puberty and premature thelarche groups.
      Increased serum levels of leptin, kisspeptin and neurokinin B in patients with
      premature thelarche and central precocious puberty suggest that they take part
      during the initiation of pubertal process, however, these markers are not able to
      differentiate patients with central precocious puberty from premature thelarche. 

PMID- 25572303
TI  - Multiple biomarker strategy based on parathyroid hormone and natriuretic peptides
      testing for improved prognosis of chronic heart failure.
AB  - Biomarkers offer new perspectives for a more personalized management of patients
      with heart failure (HF). Hyperparathyroidism is common in HF patients and
      parathyroid hormone (PTH) testing might provide added value for the
      prognostication of HF patients. Our objectives were therefore to determine the
      efficiency of multiple biomarker strategy based on PTH and natriuretic peptides
      measurement for the risk stratification of patients with HF. Circulating
      concentrations of bioactive PTH 1-84 and natriuretic peptides, B-type natriuretic
      peptide (BNP) and N-terminal proBNP (NT-proBNP), were measured with automated
      immunoassays in 45 healthy individuals and 137 HF patients with reduced left
      ventricular ejection fraction. Circulating levels of PTH 1-84 and natriuretic
      peptides were significantly increased in HF patients in comparison to HF
      patients. Over a long-term follow-up, baseline PTH 1-84 levels were related to
      the risk of cardiovascular death. Furthermore, in multiple biomarker approach,
      PTH measurement was additive to BNP and NT-proBNP testing for the cardiovascular
      risk assessment of HF patients. In conclusion, the combination of PTH 1-84 and
      natriuretic peptides testing improves the prognostication of HF patients and
      might allowed more personalized approach for risk stratification and treatment
      selection in HF patients. 

PMID- 25572305
TI  - Preliminary investigation of the thermal antinociceptive effects of codeine in
      cats.
AB  - OBJECTIVES: The aim of this study was to evaluate the potential thermal
      antinociceptive effects of oral administration of a single dose of codeine in
      cats compared with positive (buprenorphine) and negative (saline 0.9%) controls.
      METHODS: Six adult healthy cats weighing 5.14 +/- 0.6 kg were used. Skin
      temperature and thermal thresholds (TTs) were evaluated using a wireless device
      (Topcat Metrology) at baseline, 0.5, 1, 3, 6 and 10 h after treatment. In period
      1, TTs were evaluated after subcutaneous administration of saline 0.9%. In period
      2, cats were administered either oral codeine (10 mg total, 2.0 +/- 0.2 mg/kg) or
      buccal buprenorphine (0.04 mg/kg) in a cross-over, blinded study design. Half of
      the volume of buprenorphine was administered into each cheek pouch. Delta TT
      (difference between TTs after and before treatment) was used for data comparison.
      Mean +/- SD data were analyzed using one-way ANOVA followed by Dunnett's or
      Tukey's test when appropriate (P <0.05). RESULTS: Adverse effects did not occur
      in any group. Skin temperature was not different between groups nor over time.
      Temporal changes in TTs were not observed after saline or codeine. Buprenorphine
      increased Delta TT at 3 h (2.7 +/- 3.3 degrees C) when compared with baseline or
      saline (P <0.05). For buprenorphine, TTs were not >47.6 degrees C at any time
      point in four cats. The mean highest temperature recorded in the two other cats
      in that group was 54.5 and 52.8 degrees C at 3 h. CONCLUSIONS AND CLINICAL
      RELEVANCE: At the dose administered, codeine did not produce thermal
      antinociception. Mild increases in TT after buccal buprenorphine might be related
      to the first-pass effect after drug swallowing, drug spillage during
      administration and/or individual variability. These factors should be taken in to
      consideration when administering buprenorphine by this route in the clinical
      setting.

PMID- 25572306
TI  - Susceptibility of rapidly growing mycobacteria isolated from Australian cats to
      ivermectin, moxidectin, ceftiofur and florfenicol.
AB  - OBJECTIVES: Rapidly growing mycobacteria (RGM) infections in cats typically
      manifest as a panniculitis, requiring long-term antimicrobial therapy for
      resolution. The search for novel antimicrobial therapies to reduce treatment
      duration and improve the rate of clinical resolution is imperative. Accordingly,
      RGM isolates underwent susceptibility testing to some avermectins and other
      antibacterial drugs currently available. METHODS: Five Mycobacterium fortuitum
      and six Mycobacterium smegmatis isolates obtained from Australian cats underwent
      susceptibility testing by microbroth dilution to ivermectin, moxidectin,
      ceftiofur and florfenicol. RESULTS: All isolates were resistant to the highest
      concentrations of ivermectin, moxidectin and ceftiofur tested (1024 ug/ml, 256
      MUg/ml and 32 MUg/ml, respectively). All isolates of M fortuitum were resistant
      to the highest concentration of florfenicol tested (128 ug/ml). The minimum
      inhibitory concentration range of florfenicol that inhibited growth of M
      smegmatis isolates was 32-64 ug/ml. CONCLUSIONS AND RELEVANCE: All drugs appear
      to have no efficacy in vitro for the treatment of RGM infections.

PMID- 25572304
TI  - Integrins and cancer: regulators of cancer stemness, metastasis, and drug
      resistance.
AB  - Interactions between cancer cells and their surroundings can trigger essential
      signaling cues that determine cell fate and influence the evolution of the
      malignant phenotype. As the primary receptors involved in cell-matrix adhesion,
      integrins present on the surface of tumor and stromal cells have a profound
      impact on the ability to survive in specific locations, but in some cases, these
      receptors can also function in the absence of ligand binding to promote stemness
      and survival in the presence of environmental and therapeutic stresses.
      Understanding how integrin expression and function is regulated in this context
      will enable the development of new therapeutic approaches to sensitize tumors to
      therapy and suppress their metastatic phenotype. 

PMID- 25572307
TI  - Adult separation anxiety disorder: accepted but little understood.

PMID- 25572308
TI  - Serotonin reuptake inhibitors and breastfeeding: a systematic review.
AB  - OBJECTIVE: The postnatal period represents a critical phase for mothers because
      of physiological hormonal changes, the increase of emotional reactions and a
      greater susceptibility for the onset/recrudescence of psychiatric disorders.
      Despite the evidence of an increasing utilization of antidepressant drugs during
      breastfeeding, there is still few reliable information on the neonatal safety of
      the selective serotonin reuptake inhibitors (SSRIs) and selective noradrenergic
      reuptake inhibitors (SNRIs) [serotonin reuptake inhibitors (SRIs)] in nursing
      mothers. The aim of this study is to provide a systematic review on the neonatal
      safety profile of these drugs during breastfeeding, also assessing the limits of
      available tools. METHODS: MEDLINE and PubMed databases were searched without any
      language restrictions by using the following set of keywords: ((SSRIs OR
      selective serotonin inhibitor reuptake OR SNRIs OR selective serotonin
      noradrenaline inhibitor reuptake) AND (breastfeeding OR lactation OR breast
      milk)). A separate search was also performed for each SSRIs (paroxetine,
      fluvoxamine, fluoxetine, sertraline, citalopram and escitalopram) and SNRIs
      (venlafaxine and duloxetine). RESULTS: Sertraline and paroxetine show a better
      neonatal safety profile during breastfeeding as compared with other SRIs. Less
      data are available for fluvoxamine, escitalopram and duloxetine. Few studies
      followed up infants breastfeed for assessing the neurodevelopmental outcomes.
      CONCLUSIONS: Literature review clearly indicates paroxetine and sertraline as the
      drugs that should be preferred as first line choice in nursing women who need an
      antidepressant treatment.

PMID- 25572309
TI  - Increased plasma levels of soluble TNF receptors 1 and 2 in bipolar depression
      and impact of lithium treatment.
AB  - OBJECTIVE: TNF system (TNF and its soluble receptors sTNFR1 and 2) has been
      investigated as a potential molecular target in bipolar disorder. The aim of the
      study was to compare plasma levels of these receptors in unmedicated bipolar
      depressed patients compared with healthy controls, and to evaluate the effects of
      a 6-week lithium treatment on sTNFR1 and sTNFR2 levels. METHODS: The study
      enrolled 29 patients with unmedicated bipolar disorder in a major depressive
      episode and 27 matched controls. Patients had blood collected at baseline and
      after 6 weeks of lithium treatment. The concentration of sTNFRs was measured by
      ELISA. RESULTS: sTNFR1 and sTNFR2 levels were significantly increased in bipolar
      depression in comparison with healthy subjects. Lithium treatment did not
      significantly change sTNFR1 and sTNFR2 levels from baseline to endpoint. There
      was no correlation between improvement in depressive symptoms and the change in
      sTNFR1 or sTNFR1 levels. CONCLUSION: These results reinforce the involvement of
      an activated immune response system in the pathophysiology of bipolar disorder,
      with no impact of lithium treatment on the related biomarkers.

PMID- 25572312
TI  - A case of hypopituitarism and porphyria cutanea tarda in relation to estrogen
      therapy in a patient with empty sella syndrome.

PMID- 25572310
TI  - Mn-superoxide dismutase activity is associated with orofacial involuntary
      movements in schizophrenia patients with tardive dyskinesia.
AB  - BACKGROUND: Oxidative stress-induced damage may be involved in tardive dyskinesia
      (TD) development. Superoxide dismutase (SOD), the key antioxidant enzyme, was
      found abnormal in TD. OBJECTIVE: We examined the role of oxidative stress in
      relation to TD and TD subtypes in schizophrenia using manganese SOD (MnSOD) as
      the biomarker. METHODS: We recruited 152 male chronic patients with (n = 76) and
      without TD (n = 76) meeting Diagnostic and Statistical Manual of Mental Disorders
      IV criteria for schizophrenia and 75 male control subjects. We examined the MnSOD
      activity for all subjects. Positive and Negative Syndrome Scale and the Abnormal
      Involuntary Movement Scale (AIMS) were assessed in the patients. RESULTS:
      Manganese SOD activity was lower in patients with TD than non-TD (p < 0.05). In
      the patients with TD, orofacial and total scores of AIMS were positively
      associated with MnSOD levels (both p < 0.05). Multiple regression analysis
      further confirmed that MnSOD was an independent contributor to both the orofacial
      and the total scores of AIMS (both p < 0.05). CONCLUSIONS: Oxidative stress
      reflected by compromised oxidative defense may play a role in the development and
      severity of TD. There may be an etiologic relationship between increased SOD
      level and dyskinetic movements associated with TD. In particular, MnSOD activity
      may have a specific role in orofacial TD.

PMID- 25572313
TI  - Cryptotanshinone, an orally bioactive herbal compound from Danshen, attenuates
      atherosclerosis in apolipoprotein E-deficient mice: role of lectin-like oxidized
      LDL receptor-1 (LOX-1).
AB  - BACKGROUND AND PURPOSE: Cryptotanshinone (CTS) is a major bioactive diterpenoid
      isolated from Danshen, an eminent medicinal herb that is used to treat
      cardiovascular disorders in Asian medicine. However, it is not known whether CTS
      can prevent experimental atherosclerosis. The present study was designed to
      investigate the protective effects of CTS on atherosclerosis and its molecular
      mechanisms of action. EXPERIMENTAL APPROACH: Apolipoprotein E-deficient (ApoE(-/
      )) mice, fed an atherogenic diet, were dosed daily with CTS (15, 45 mg kg(-1)
      day(-1)) by oral gavage. In vitro studies were carried out in oxidized LDL
      (oxLDL)-stimulated HUVECs treated with or without CTS. KEY RESULTS: CTS
      significantly attenuated atherosclerotic plaque formation and enhanced plaque
      stability in ApoE(-/-) mice by inhibiting the expression of lectin-like oxLDL
      receptor-1 (LOX-1) and MMP-9, as well as inhibiting reactive oxygen species (ROS)
      generation and NF-kappaB activation. CTS treatment significantly decreased the
      levels of serum pro-inflammatory mediators without altering the serum lipid
      profile. In vitro, CTS decreased oxLDL-induced LOX-1 mRNA and protein expression
      and, thereby, inhibited LOX-1-mediated adhesion of monocytes to HUVECs, by
      reducing the expression of adhesion molecules (intracellular adhesion molecule 1
      and vascular cellular adhesion molecule 1). Furthermore, CTS inhibited NADPH
      oxidase subunit 4 (NOX4)-mediated ROS generation and consequent activation of NF
      kappaB in HUVECs. CONCLUSIONS AND IMPLICATIONS: CTS was shown to have anti
      atherosclerotic activity, which was mediated through inhibition of the LOX-1
      mediated signalling pathway. This suggests that CTS is a vasculoprotective drug
      that has potential therapeutic value for the clinical treatment of
      atherosclerotic cardiovascular diseases.

PMID- 25572314
TI  - Patient-specific driver gene prediction and risk assessment through integrated
      network analysis of cancer omics profiles.
AB  - Extensive and multi-dimensional data sets generated from recent cancer omics
      profiling projects have presented new challenges and opportunities for unraveling
      the complexity of cancer genome landscapes. In particular, distinguishing the
      unique complement of genes that drive tumorigenesis in each patient from a sea of
      passenger mutations is necessary for translating the full benefit of cancer
      genome sequencing into the clinic. We address this need by presenting a data
      integration framework (OncoIMPACT) to nominate patient-specific driver genes
      based on their phenotypic impact. Extensive in silico and in vitro validation
      helped establish OncoIMPACT's robustness, improved precision over competing
      approaches and verifiable patient and cell line specific predictions (2/2 and 6/7
      true positives and negatives, respectively). In particular, we computationally
      predicted and experimentally validated the gene TRIM24 as a putative novel
      amplified driver in a melanoma patient. Applying OncoIMPACT to more than 1000
      tumor samples, we generated patient-specific driver gene lists in five different
      cancer types to identify modes of synergistic action. We also provide the first
      demonstration that computationally derived driver mutation signatures can be
      overall superior to single gene and gene expression based signatures in enabling
      patient stratification and prognostication. Source code and executables for
      OncoIMPACT are freely available from http://sourceforge.net/projects/oncoimpact. 

PMID- 25572315
TI  - Specific and non-specific interactions of ParB with DNA: implications for
      chromosome segregation.
AB  - The segregation of many bacterial chromosomes is dependent on the interactions of
      ParB proteins with centromere-like DNA sequences called parS that are located
      close to the origin of replication. In this work, we have investigated the
      binding of Bacillus subtilis ParB to DNA in vitro using a variety of biochemical
      and biophysical techniques. We observe tight and specific binding of a ParB
      homodimer to the parS sequence. Binding of ParB to non-specific DNA is more
      complex and displays apparent positive co-operativity that is associated with the
      formation of larger, poorly defined, nucleoprotein complexes. Experiments with
      magnetic tweezers demonstrate that non-specific binding leads to DNA condensation
      that is reversible by protein unbinding or force. The condensed DNA structure is
      not well ordered and we infer that it is formed by many looping interactions
      between neighbouring DNA segments. Consistent with this view, ParB is also able
      to stabilize writhe in single supercoiled DNA molecules and to bridge segments
      from two different DNA molecules in trans. The experiments provide no evidence
      for the promotion of non-specific DNA binding and/or condensation events by the
      presence of parS sequences. The implications of these observations for chromosome
      segregation are discussed. 

PMID- 25572316
TI  - Inter-individual variability contrasts with regional homogeneity in the human
      brain DNA methylome.
AB  - The possibility that alterations in DNA methylation are mechanistic drivers of
      development, aging and susceptibility to disease is widely acknowledged, but
      evidence remains patchy or inconclusive. Of particular interest in this regard is
      the brain, where it has been reported that DNA methylation impacts on neuronal
      activity, learning and memory, drug addiction and neurodegeneration. Until
      recently, however, little was known about the 'landscape' of the human brain
      methylome. Here we assay 1.9 million CpGs in each of 43 brain samples
      representing different individuals and brain regions. The cerebellum was a
      consistent outlier compared to all other regions, and showed over 16 000
      differentially methylated regions (DMRs). Unexpectedly, the sequence
      characteristics of hypo- and hypermethylated domains in cerebellum were distinct.
      In contrast, very few DMRs distinguished regions of the cortex, limbic system and
      brain stem. Inter-individual DMRs were readily detectable in these regions. These
      results lead to the surprising conclusion that, with the exception of cerebellum,
      DNA methylation patterns are more homogeneous between different brain regions
      from the same individual, than they are for a single brain region between
      different individuals. This finding suggests that DNA sequence composition, not
      developmental status, is the principal determinant of the human brain DNA
      methylome. 

PMID- 25572317
TI  - Transcriptional inhibition and mutagenesis induced by N-nitroso compound-derived
      carboxymethylated thymidine adducts in DNA.
AB  - N-nitroso compounds represent a common type of environmental and endogenous DNA
      damaging agents. After metabolic activation, many N-nitroso compounds are
      converted into a diazoacetate intermediate that can react with nucleobases to
      give carboxymethylated DNA adducts such as N3-carboxymethylthymidine (N3-CMdT)
      and O(4)-carboxymethylthymidine (O(4)-CMdT). In this study, we constructed non
      replicative plasmids carrying a single N3-CMdT or O(4)-CMdT, site-specifically
      positioned in the transcribed strand, to investigate how these lesions compromise
      the flow of genetic information during transcription. Our results revealed that
      both N3-CMdT and O(4)-CMdT substantially inhibited DNA transcription mediated by
      T7 RNA polymerase or human RNA polymerase II in vitro and in human cells. In
      addition, we found that N3-CMdT and O(4)-CMdT were miscoding lesions and
      predominantly directed the misinsertion of uridine and guanosine, respectively.
      Our results also suggested that these carboxymethylated thymidine lesions may
      constitute efficient substrates for transcription-coupled nucleotide excision
      repair in human cells. These findings provided important new insights into the
      biological consequences of the carboxymethylated DNA lesions in living cells. 

PMID- 25572318
TI  - A 750,000 year old hominin molar from the site of Nadung'a, West Turkana, Kenya.

PMID- 25572319
TI  - The Swedish Exercise Self-Efficacy Scale (ESES-S): reliability and validity in a
      rheumatoid arthritis population.
AB  - PURPOSE: The aim of the present study was to investigate aspects of reliability
      and validity of the Exercise Self-Efficacy Scale (ESES-S) in a rheumatoid
      arthritis (RA) population. METHODS: A total of 244 people with RA participating
      in a physical activity study were included. The six-item ESES-S, exploring
      confidence in performing exercise, was assessed for test-retest reliability over
      4-6 months, and for internal consistency. Construct validity investigated
      correlation with similar and other constructs. RESULTS: An intraclass correlation
      coefficient (ICC) of 0.59 (95% CI 0.37-0.73) was found for 84 participants with
      stable health perceptions between measurement occasions. Cronbach's alpha
      coefficients of 0.87 and 0.89 were found at the first and second measurements.
      Corrected item-total correlation single ESES-S items ranged between 0.53 and
      0.73. Construct convergent validity for the ESES-S was partly confirmed by
      correlations with health-enhancing physical activity and outcome expectations
      respectively (Pearson's r = 0.18, p < 0.01). Construct divergent validity was
      confirmed by the absence of correlations with age or gender. No floor or ceiling
      effects were found for ESES-S. CONCLUSIONS: The results indicate that the ESES-S
      has moderate test-retest reliability and respectable internal consistency in
      people with RA. Construct validity was partially supported in the present sample.
      Further research on construct validity of the ESES-S is recommended. IMPLICATIONS
      FOR REHABILITATION: Physical exercise is crucial for management of symptoms and
      co-morbidity in rheumatoid arthritis. Self-efficacy for exercise is important to
      address in rehabilitation as it regulates exercise motivation and behavior.
      Measurement properties of self-efficacy scales need to be assessed in specific
      populations and different languages.

PMID- 25572320
TI  - The History of Acromegaly.
AB  - Pierre Marie coined the term 'acromegaly' in 1886 and linked it to a distinct
      clinical disease with a characteristic clinical picture. However, Pierre Marie
      was not the first physician to give a full record of the clinical picture of
      acromegaly; others had preceded him, like the Dutch physician Johannes Wier.
      After Marie, pituitary enlargement was noted in almost all patients with
      acromegaly. Subsequently it was discovered that pituitary hyperfunction caused by
      a pituitary tumour was indeed the cause of acromegaly. The cause of acromegaly
      could be further determined after the discovery of growth hormone (GH) and
      insulin-like growth factor I (IGF-I) and after demonstrating an association with
      GH hypersecretion and elevated circulating IGF-I. From the beginning of the 20th
      century, acromegaly could be treated by pituitary surgery and/or radiotherapy.
      After 1970, medical therapies were introduced that could control acromegaly.
      First, dopamine agonists were introduced, followed by somatostatin analogues and
      GH receptor blockers. 

PMID- 25572321
TI  - Postmortem angiography in computed tomography and magnetic resonance imaging in a
      case of fatal hemorrhage due to an arterio-venous malformation in the brain.
AB  - Autopsy is the traditional gold standard for determining the cause and manner of
      death in a forensic death investigation. However, postmortem imaging plays an
      ever-growing role in preliminary examination, even replacing conventional autopsy
      in some cases. This case report presents a case of massive intra-axial brain
      hemorrhage due to an arterio-venous malformation. The cause and manner of death
      were exclusively determined by postmortem radiology. Based on radiological
      findings, the autopsy was considered redundant and cancelled by the public
      prosecutor. 

PMID- 25572322
TI  - New frontiers in aortic therapy: focus on current trials and devices in
      transcatheter aortic valve replacement.
AB  - The first decade of clinical experience with transcatheter aortic valve
      replacement since 2002 saw the development of 2 main valve systems, namely the
      Edwards Sapien balloon-expandable valve series and the Medtronic self-expanding
      CoreValve. These 2 valve platforms now have achieved commercial approval and
      application worldwide in patients with severe aortic stenosis whose perioperative
      risk for surgical intervention is high or extreme. In the second decade of
      transcatheter aortic valve replacement, clinical experience and refinements in
      valve design have resulted in clinical drift towards lower patient risk cohorts.
      There are currently 2 major trials, PARTNER II and SURTAVI, that are both
      evaluating the role of transcatheter aortic valve replacement in intermediate
      risk patient cohorts. The results from these landmark trials may usher in a new
      clinical paradigm for transcatheter aortic valve replacement in its second
      decade. 

PMID- 25572325
TI  - Using community-level metrics to monitor the effects of marine protected areas on
      biodiversity.
AB  - Marine protected areas (MPAs) are used to protect species, communities, and their
      associated habitats, among other goals. Measuring MPA efficacy can be
      challenging, however, particularly when considering responses at the community
      level. We gathered 36 abundance and 14 biomass data sets on fish assemblages and
      used meta-analysis to evaluate the ability of 22 distinct community diversity
      metrics to detect differences in community structure between MPAs and nearby
      control sites. We also considered the effects of 6 covariates-MPA size and age,
      MPA size and age interaction, latitude, total species richness, and level of
      protection-on each metric. Some common metrics, such as species richness and
      Shannon diversity, did not differ consistently between MPA and control sites,
      whereas other metrics, such as total abundance and biomass, were consistently
      different across studies. Metric responses derived from the biomass data sets
      were more consistent than those based on the abundance data sets, suggesting that
      community-level biomass differs more predictably than abundance between MPA and
      control sites. Covariate analyses indicated that level of protection, latitude,
      MPA size, and the interaction between MPA size and age affect metric performance.
      These results highlight a handful of metrics, several of which are little known,
      that could be used to meet the increasing demand for community-level indicators
      of MPA effectiveness.

PMID- 25572324
TI  - Neonatal Hyperoxia Exposure Induces Kidney Fibrosis in Rats.
AB  - BACKGROUND: Human and animal studies have demonstrated that neonatal hyperoxia
      increases oxidative stress and adversely affects glomerular and tubular maturity.
      This study was undertaken to determine how exposure to neonatal hyperoxia
      affected kidney morphology and fibrosis and to elucidate the relationship between
      connective tissue growth factor (CTGF) and collagen expression in rat kidneys.
      METHODS: Sprague-Dawley rat pups were exposed to either hyperoxia or ambient air.
      The control groups were maintained in ambient air for 1 week and 3 weeks. The
      hyperoxia groups were exposed to >95% O2 for 1 week and subsequently placed in an
      environment of 60% O2 for an additional 2 weeks. The animals were euthanized on
      Postnatal Day 7 or 21 and the kidneys underwent histological analyses and
      oxidative stress and total collagen measurements. RESULTS: The rats reared in O2
      enriched air exhibited significantly higher tubular injury scores (1.4 +/- 0.5
      vs. 0.7 +/- 0.7 on Day 7; 1.4 +/- 0.5 vs. 0.6 +/- 0.5 on Day 21), a larger
      proportion of the cortex occupied by glomeruli (25.5 +/- 4.1 vs. 21.3 +/- 3.1% on
      Day 7; 20.1 +/- 3.5 vs. 17.1 +/- 1.7% on Day 21), larger glomerular sizes (84.7
      +/- 5.8 vs. 77.5 +/- 6.1 MUm on Day 7; 88.4 +/- 2.9 vs. 84.9 +/- 3.1 MUm on Day
      21), and higher total collagen content (54.1 +/- 27.5 vs. 18.3 +/- 6.3 MUg/mg
      protein on Day 7; 397.4 +/- 32.8 vs. 289.5 +/- 80.0 MUg/mg protein on Day 21)
      than did rats reared in ambient air. Immunohistochemical expressions of oxidative
      stress marker 8-hydroxy-2'-deoxyguanosine and CTGF immunoreactivities were
      significantly higher in the rats reared in O2-enriched air compared with the rats
      reared in ambient air on Postnatal Days 7 and 21. CONCLUSION: Neonatal hyperoxia
      exposure contributes to kidney fibrosis, which is probably caused by activated
      CTGF expression.

PMID- 25572326
TI  - A retrospective comparison of microwave ablation and high intensity focused
      ultrasound for treating symptomatic uterine fibroids.
AB  - OBJECTIVES: To retrospectively compare the effectiveness and safety of
      percutaneous microwave ablation (PMWA) and ultrasound-guided high-intensity
      focused ultrasound (USgHIFU) for treating symptomatic uterine fibroids. METHODS:
      Seventy-three women with symptomatic uterine fibroids who met the inclusion
      criteria were enrolled in our study from September 2012 to December 2013. Thirty
      one patients with forty uterine fibroids underwent PMWA, and forty-two patients
      with fifty-one uterine fibroids underwent USgHIFU. A contrast-enhanced MRI was
      performed before and after treatment, and all patients were followed up for 6
      months. Assessment endpoints included symptom severity scores (SSS), treatment
      time, ablation rate, fibroid regression rate and adverse events. RESULTS: The
      mean age of the patients in our study was 35.4+/-6.2 years (range, 21-49 years),
      and the median volume of uterine fibroids was 95.7cm(3) (60.3-131.5cm(3)). The
      ablation rate of uterine fibroids was 79.8+/-18.2% and 77.1+/-14.9% in the PMWA
      group and the USgHIFU group, respectively, and showed no significant difference
      between the groups. Changes in SSS after PMWA were similar in the PMWA group
      (47.7 pre-treatment vs. 29.9 post-treatment) and USgHIFU group (42.1 pre
      treatment vs. 24.6 post-treatment). The regression rate of uterine fibroids also
      showed no marked difference between the two groups (PMWA, 50.3%; USgHIFU, 52.4%).
      The median treatment time of the PMWA group was 46.2min, which was demonstrably
      superior to USgHIFU. Finally, the occurrence rate of adverse events was the same
      in the two groups. CONCLUSIONS: The safety and effectiveness of PMWA and USgHIFU
      in the treatment of uterine fibroids were similar; however, the median treatment
      time of PMWA was shorter than that of USgHIFU.

PMID- 25572323
TI  - Alcohol confounds relationship between cannabis misuse and psychosis conversion
      in a high-risk sample.
AB  - OBJECTIVE: Cannabis use has been examined as a predictor of psychosis in clinical
      high-risk (CHR) samples, but little is known about the impact of other substances
      on this relationship. METHOD: Substance use was assessed in a large sample of CHR
      participants (N = 370, mean age = 18.3) enrolled in the multisite North American
      Prodrome Longitudinal Study Phase 1 project. Three hundred and forty-one
      participants with cannabis use data were divided into groups: No Use (NU, N =
      211); Cannabis Use without impairment (CU, N = 63); Cannabis Abuse/Dependence
      (CA/CD, N = 67). Participants (N = 283) were followed for >=2 years to determine
      psychosis conversion. RESULTS: Alcohol (45.3%) and cannabis (38.1%) were the most
      common substances. Cannabis use groups did not differ on baseline attenuated
      positive symptoms. Seventy-nine of 283 participants with cannabis and follow-up
      data converted to psychosis. Survival analysis revealed significant differences
      between conversion rates in the CA/CD group compared with the No Use (P = 0.031)
      and CU group (P = 0.027). CA/CD also significantly predicted psychosis in a
      regression analysis, but adjusting for alcohol use weakened this relationship.
      CONCLUSION: The cannabis misuse and psychosis association was confounded by
      alcohol use. Non-impairing cannabis use was not related to psychosis. Results
      highlight the need to control for other substance use, so as to not overstate the
      cannabis/psychosis connection.

PMID- 25572327
TI  - The antigenic repertoire of premalignant and high-risk lesions.
AB  - Prophylactic vaccines have been a major advance in preventing the development of
      infections after exposure to pathogens. When contemplating an effective approach
      to cancer prevention, vaccines offer unique advantages over other more standard
      approaches: First, once appropriately stimulated, antigen-specific T cells will
      travel to all sites of disease and eradicate cells bearing the proteins to which
      the T cells have been primed by vaccination. Second, successful immunization will
      further result in the development of immunologic memory, providing lifelong
      immunologic surveillance. There is evidence of an adaptive tumor immune
      infiltrate even at the earliest stages of breast and colon cancer development.
      Furthermore, there is measurable immunity to lesion-associated antigens present
      in patients who will eventually develop malignancy even before cancer is
      clinically evident. Recent studies are beginning to unmask the preinvasive
      antigenic repertoire for these two malignancies. Preliminary experiments in
      transgenic mouse models of mammary and intestinal tumors suggest that
      immunization against antigens expressed in preinvasive and high-risk lesions may
      be effective in preventing the development of invasive malignancy.

PMID- 25572328
TI  - Presentation blood glucose and death, hospitalization, and future diabetes risk
      in patients with acute heart failure syndromes.
AB  - PURPOSE: The prognostic implications of blood glucose on a wide range of outcomes
      including early mortality, hospitalizations, and incident diabetes diagnoses have
      not been fully elucidated in acute heart failure syndromes (AHFS). METHODS: In a
      population-based cohort of 16 524 AHFS patients presenting to the emergency
      department (ED) in Ontario, Canada between 2004 and 2007, we performed a
      competing risk analysis for 30-day mortality, new diabetes diagnoses, and
      hospitalization outcomes. Presentation blood glucose concentrations were
      categorized as follows: 3.9-6.1 [referent], >6.1-7.8, >7.8-9.4, >9.4-11.1, and
      >11.1 mmol/L. RESULTS: Among AHFS patients without diabetes presenting to the ED
      (n = 9275), blood glucose >6.1 mmol/L (n = 5252, 56.6%) was associated with
      increased risks of all-cause death [hazard ratio (HR) range: 1.26 (95% CI 1.05
      1.50) to 1.50 (95% CI 1.11-2.02)], and cardiovascular death [HR range: 1.28 (95%
      CI 1.03-1.59) to 1.64 (95% CI 1.16-2.33)]. Among AHFS patients with diabetes (n =
      7249), presenting blood glucose >11.1 mmol/L (n = 2286, 31.5%) was associated
      with increased risks of all-cause death (HR 1.48, 95% CI 1.10-2.00) and diabetes
      related hospitalizations (HR 1.39, 95% CI; 1.20-1.61). Presentation blood glucose
      >9.4 mmol/L was associated with increased risks of hospitalization for HF or
      cardiovascular causes [HR range: 1.09 (95% CI 1.02-1.17) to 1.15 (95% CI 1.07
      1.24)] in all patients. With higher presentation blood glucose, the risk of
      incident diabetes diagnosis increased, with adjusted HRs of 1.61 (>6.1-7.8
      mmol/L) to 3.61 (>11.1 mmol/L) among those without the condition at baseline (all
      P < 0.001). CONCLUSIONS: Mildly elevated presentation blood glucose was
      associated with early death, future diabetes, and hospitalizations for diabetes,
      HF, and cardiovascular causes among patients with AHFS.

PMID- 25572330
TI  - Dyspareunia and its comorbidities among Taiwanese women: analysis of the 2004
      2010 Nationwide Health Insurance Database.
AB  - INTRODUCTION: Most of the existing studies on dyspareunia only focus on
      qualitative observations. These measurement tools may not reflect the actual
      situation of dyspareunia in Taiwan. AIM: This study aimed to estimate the
      incidence of dyspareunia in Taiwan and investigate dyspareunia-associated
      comorbidities using the National Health Insurance Research Database (NHIRD).
      METHODS: This study is a population-based retrospective cohort investigation.
      MAIN OUTCOME MEASURES: We analyzed the 2004-2010 claims data on dyspareunia from
      the NHIRD. Dyspareunia was identified by outpatient visits using International
      Classification of Diseases, Ninth Revision, Clinical Modification (diagnosis code
      6250). Patients who visited as outpatients with dyspareunia after the index date
      were considered to have comorbidities associated with dyspareunia medical
      conditions. The index events included vaginal disorders, vulvar disorders,
      uterine and ovarian factors, female genital organ and menstrual cycle disorders,
      menopause, and relative abdominopelvic organ disorders. The incidence of
      dyspareunia among different age groups was determined. The location and areas
      significantly related to the physical gynecology or relative pelvic organ causing
      the disease were also analyzed. RESULTS: A total of 978 females of different ages
      had experienced dyspareunia. The incidence of dyspareunia was higher among
      individuals aged 30-34 years. The findings of this study indicated that
      dyspareunia was comorbid with menopause, pelvic floor dysfunction, and most
      gynecological infections. In particular, the more common physical causes of
      dyspareunia were introitus and vaginal infections (19.95%), menopause (16.80%),
      female genital organ and menstrual cycle disorders (15.22%), and female pelvic
      organ infections (13.65%). CONCLUSIONS: This study posits that women of all ages
      (20-70 years) experience painful sexual intercourse. This large-scale nationwide
      claims-based study showed that menopause and pelvic infection disorder were
      dyspareunia-related comorbidities. Moreover, gynecological infections and pelvic
      floor dysfunctions were associated with dyspareunia.

PMID- 25572329
TI  - Phase II study of panobinostat in combination with bevacizumab for recurrent
      glioblastoma and anaplastic glioma.
AB  - BACKGROUND: Panobinostat is a histone deacetylase inhibitor with antineoplastic
      and antiangiogenic effects in glioma that may work synergistically with
      bevacizumab. We conducted a multicenter phase II trial of panobinostat combined
      with bevacizumab in patients with recurrent high-grade glioma (HGG). METHODS:
      Patients with recurrent HGG were treated with oral panobinostat 30 mg 3 times per
      week, every other week, in combination with bevacizumab 10 mg/kg every other
      week. The primary endpoint was a 6-month progression-fee survival (PFS6) rate for
      participants with recurrent glioblastoma (GBM). Patients with recurrent
      anaplastic glioma (AG) were evaluated as an exploratory arm of the study.
      RESULTS: At interim analysis, the GBM arm did not meet criteria for continued
      accrual, and the GBM arm was closed. A total of 24 patients with GBM were accrued
      prior to closure. The PFS6 rate was 30.4% (95%, CI 12.4%-50.7%), median PFS was 5
      months (range, 3-9 months), and median overall survival (OS) was 9 months (range,
      6-19 months). Accrual in the AG arm continued to completion, and a total of 15
      patients were enrolled. The PFS6 rate was 46.7% (range, 21%-73%), median PFS was
      7 months (range, 2-10 months), and median OS was 17 months (range, 5 months-27
      months). CONCLUSIONS: This phase II study of panobinostat and bevacizumab in
      participants with recurrent GBM did not meet criteria for continued accrual, and
      the GBM cohort of the study was closed. Although it was reasonably well
      tolerated, the addition of panobinostat to bevacizumab did not significantly
      improve PFS6 compared with historical controls of bevacizumab monotherapy in
      either cohort.

PMID- 25572332
TI  - The Outcome and Predictors of Mortality in Patients Therapeutically Cooled
      Postcardiac Arrest.
AB  - PURPOSE: To review the outcomes of patients postcardiac arrest admitted to a
      metropolitan intensive care unit (ICU) where therapeutic hypothermia is
      practiced. MATERIALS AND METHODS: Patients admitted from 2004 to 2012 were
      reviewed. The management protocol included cooling to 33 degrees C for 24 hours.
      The primary outcome assessed was hospital mortality. Secondary outcome measures
      included mortality in patients admitted to ICU after in-hospital cardiac arrest
      (IHCA) when compared to those with out-of-hospital cardiac arrest (OHCA) and to
      review initial cardiac rhythm as an indicator of mortality. RESULTS: A total of
      330 patients were included. The overall hospital mortality was 58.1%. Hospital
      mortality was significantly higher in patients who had OHCA when compared to IHCA
      (62.5% vs 51%; P = .04). Patients who had asystole and pulseless electrical
      activity (PEA) had a higher mortality when compared to ventricular
      tachycardia/ventricular fibrillation (VT/VF) arrest (81.7% vs 67.8% vs 41.9%,
      respectively; P < .01). CONCLUSION: Patients admitted to ICU postcardiac arrest
      after therapeutic cooling have a high mortality. An initial rhythm of VT/VF
      confers a mortality benefit when compared to asystole and PEA.

PMID- 25572335
TI  - Relationship between anticipatory socialization experiences and first-year
      veterinary students' career interests.
AB  - The purpose of this project was to explore first-year veterinary students'
      anticipatory socialization-life, education, and social experiences that assist in
      preparation for professional occupations-and determine what relationship exists
      between those experiences and career interests. Seventy-three first-year
      veterinary students enrolled in the Careers in Veterinary Medicine course
      completed the Veterinary Careers survey. Results show that students' anticipatory
      vocational socialization experiences are significantly related to their stated
      career interests. The career interests with the highest percentage of students
      expressing "a great deal of interest" included specialty private practice (37%),
      research and teaching in an academic setting (33%), and international veterinary
      medicine (31%). The career interests with the highest percentage of students
      expressing "no interest at all" included the military (50%), equine private
      practice (42%), and the pharmaceutical industry (41%). Less than half of the
      students (42%) stated that they reconsidered their career path after the first
      semester of veterinary school, but the majority (87%) developed a better
      understanding of how to pursue a nontraditional career path should they choose to
      do so. 

PMID- 25572334
TI  - The product of triglycerides and glucose in comparison with fasting plasma
      glucose did not improve diabetes prediction.
AB  - AIMS: Previous study has reported that triglycerides-glucose (TyG) index, a
      product of triglycerides and fasting plasma glucose (FPG), might be useful in the
      prediction of incident type 2 diabetes (T2D). We evaluated the ability of the TyG
      index compared to FPG and OGTT as possible diabetes predictor in nondiabetic
      first-degree relatives (FDRs) of patients with T2D. METHODS: A total of 1,488
      FDRs without diabetes of consecutive patients with T2D 30-70 years old (361 men
      and 1,127 women) were examined and followed for a mean (SD) of 6.9 (1.7) years
      for diabetes incidence. We examined the incidence of diabetes across quartiles of
      the TyG index and plotted a receiver operating characteristic (ROC) curve to
      assess discrimination. At baseline and through follow-up, participants underwent
      a standard 75-g two-hour oral glucose tolerance test. RESULTS: During 10,124
      person-years of follow-up, 41 men and 154 women developed T2D. Those in the top
      quartile of TyG index were 3.4 times more likely to develop T2D than those in the
      bottom quartile (odds ratio 3.36; 95 % CI 1.83, 6.19). On ROC curve analysis, a
      higher area under the ROC was found for FPG (76.2; 95 % CI 71.9, 80.6), 1-hPG
      (81.0, 95 % CI 77.2, 84.9) and 2-hPG (76.5; 95 % CI 72.3, 80.8) than for TyG
      index (65.1; 95 % CI 60.5, 69.7). CONCLUSIONS: TyG index is predicted T2D in high
      risk individuals in Iran but FPG, 1-hPG and 2-hPG appeared to be more robust
      predictor of T2D in our study population.

PMID- 25572331
TI  - RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating
      the tumor microenvironment.
AB  - RAGE is a multifunctional receptor implicated in diverse processes including
      inflammation and cancer. In this study, we report that RAGE expression is
      upregulated widely in aggressive triple-negative breast cancer (TNBC) cells, both
      in primary tumors and in lymph node metastases. In evaluating the functional
      contributions of RAGE in breast cancer, we found that RAGE-deficient mice
      displayed a reduced propensity for breast tumor growth. In an established model
      of lung metastasis, systemic blockade by injection of a RAGE neutralizing
      antibody inhibited metastasis development. Mechanistic investigations revealed
      that RAGE bound to the proinflammatory ligand S100A7 and mediated its ability to
      activate ERK, NF-kappaB, and cell migration. In an S100A7 transgenic mouse model
      of breast cancer (mS100a7a15 mice), administration of either RAGE neutralizing
      antibody or soluble RAGE was sufficient to inhibit tumor progression and
      metastasis. In this model, we found that RAGE/S100A7 conditioned the tumor
      microenvironment by driving the recruitment of MMP9-positive tumor-associated
      macrophages. Overall, our results highlight RAGE as a candidate biomarker for
      TNBCs, and they reveal a functional role for RAGE/S100A7 signaling in linking
      inflammation to aggressive breast cancer development.

PMID- 25572333
TI  - High prevalence of vitamin D deficiency and lack of association with subclinical
      atherosclerosis in asymptomatic patients with Type 1 Diabetes Mellitus from a
      Mediterranean area.
AB  - AIMS: Several studies linked vitamin D deficiency with coronary artery disease
      (CAD). The aim of this study was to evaluate the relationship between the
      concentrations of 25-hydroxyvitamin D (25OHD) and the presence of early
      atherosclerosis in asymptomatic Type 1 Diabetes (T1D) patients with no previous
      history of ischemic heart disease. METHODS: One hundred and forty-five patients
      with T1D (age 37.8 +/- 8 years, 57 % male, all Caucasian, disease duration 20.6
      +/- 8.3 years, HbA1c 7.6 +/- 1.4 % (60.2 +/- 11.1 mmol/mol), body mass index
      (BMI) 25.2 +/- 3.5 kg/m2, 52.4 % smokers, 23 % retinopathy, 10 % nephropathy) and
      48 controls matched for age, sex, BMI and smoking habit were studied. 25OHD
      deficiency was defined for values <=20 ng/mL. A sun exposure questionnaire,
      carotid ultrasonography to determine carotid intima-media thickness (CIMT) and
      the presence of atheroma plaques and cardiac computed tomography for evaluation
      of calcium artery calcification (CACS) were performed. RESULTS: T1D subjects
      showed a high proportion of 25OHD deficiency (43.2 % vs. 21.7 %, p = 0.032). Of
      all, 82 % of T1D patients and 92 % of controls had a calcium score of 0. CIMT was
      greater in patients with T1D (0.55 +/- 0.14 mm vs 0.48 +/- 0.15, p = 0.01)
      compared with controls. T1D subjects showed no differences in the results of CACS
      or CIMT according to the vitamin D concentrations. CONCLUSIONS: T1D patients have
      lower concentrations and twice more prevalence of 25OHD deficiency than controls.
      There was no association between 25OHD concentrations and subclinical CAD.

PMID- 25572336
TI  - Teaching biostatistics and epidemiology in the veterinary curriculum: what do our
      fellow lecturers expect?
AB  - Given veterinary students' varying mathematical knowledge and interest in
      statistics, teaching statistical concepts to them is often seen as a challenge.
      Consequently, there is an ongoing debate among lecturers about the best time to
      introduce the material into the curriculum, and the best thematic content and
      conceptual approach to teaching in basic biostatistics classes. During a workshop
      meeting of epidemiology and biostatistics lecturers of Austrian, German, and
      Swiss veterinary schools, the question was raised as to whether the topics taught
      in epidemiology and statistics classes are of sufficient relevance to our
      lecturing colleagues in other fields of veterinary education (i.e., whether our
      colleagues have certain expectations as to what the students should know about
      biostatistics before taking their classes). In 2012, an online survey was
      compiled and carried out at all eight German-speaking veterinary schools to
      address this issue. There were 266 respondents out of approximately 800 contacted
      lecturers from all schools and disciplines. Almost 50% responded that the basic
      biostatistics class should be taught early on (in the second or third year),
      while only 26% indicated that basic epidemiology should commence before the third
      year of the veterinary curriculum. There were clear differences in perceived
      relevance of the 44 epidemiological and biostatistical topics presented in the
      survey, assessed on a Likert scale from 0 (no relevance) to 4 (very high
      relevance). The results provide important information about how to revise the
      content of epidemiology and biostatistics classes, and the approach could also be
      used for other courses within the veterinary curriculum with a natural science
      focus. 

PMID- 25572337
TI  - The neuromuscular activity of Bothriopsis bilineata smaragdina (forest viper)
      venom and its toxin Bbil-TX (Asp49 phospholipase A2) on isolated mouse nerve
      muscle preparations.
AB  - The presynaptic action of Bothriopsis bilineata smaragdina (forest viper) venom
      and Bbil-TX, an Asp49 PLA2 from this venom, was examined in detail in mouse
      phrenic nerve-muscle (PND) preparations in vitro and in a neuroblastoma cell line
      (SK-N-SH) in order to gain a better insight into the mechanism of action of the
      venom and associated Asp49 PLA2. In low Ca(2+) solution, venom (3MUg/ml) caused a
      quadriphasic response in PND twitch height whilst at 10MUg/ml the venom
      additionally induced an abrupt and marked initial contracture followed by
      neuromuscular facilitation, rhythmic oscillations of nerve-evoked twitches,
      alterations in baseline and progressive blockade. The venom slowed the relaxation
      phase of muscle twitches. In low Ca(2+), Bbil-TX [210nM (3MUg/ml)] caused a
      progressive increase in PND twitch amplitude but no change in the decay time
      constant. Venom (10MUg/ml) and Bbil-TX (210nM) caused minor changes in the
      compound action potential (CAP) amplitude recorded from sciatic nerve
      preparations, with no significant effect on rise time and latency; tetrodotoxin
      (3.1nM) blocked the CAP at the end of the experiments. In mouse triangularis
      sterni nerve-muscle (TSn-m) preparations, venom (10MUg/ml) and Bbil-TX (210nM)
      significantly reduced the perineural waveform associated with the outward K(+)
      current while the amplitude of the inward Na(+) current was not significantly
      affected. Bbil-TX (210nM) caused a progressive increase in the quantal content of
      TSn-m preparations maintained in low Ca(2+) solution. Venom (3MUg/ml) and toxin
      (210nM) increased the calcium fluorescence in SK-N-SH neuroblastoma cells loaded
      with Fluo3 AM and maintained in low or normal Ca(2+) solution. In normal Ca(2+),
      the increase in fluorescence amplitude was accompanied by irregular and frequent
      calcium transients. In TSn-m preparations loaded with Fluo4 AM, venom (10MUg/ml)
      caused an immediate increase in intracellular Ca(2+) followed by oscillations in
      fluorescence and muscle contracture; Bbil-TX did not change the calcium
      fluorescence in TSn-m preparations. Immunohistochemical analysis of toxin-treated
      PND preparations revealed labeling of junctional ACh receptors but a loss of the
      presynaptic proteins synaptophysin and SNAP25. Together, these data confirm the
      presynaptic action of Bbil-TX and show that it involves modulation of K(+)
      channel activity and presynaptic protein expression. 

PMID- 25572338
TI  - Changes in swainsonine, calystegine, and nitrogen concentrations on an annual
      basis in Ipomoea carnea.
AB  - Ipomoea carnea, a swainsonine containing plant, is known to cause a neurologic
      disease in grazing livestock in Brazil and other parts of the world. To better
      understand the relative toxicity and nutritional content of I. carnea we
      investigated swainsonine, calystegine, and crude protein concentrations in leaves
      of I. carnea on a monthly basis for one year in northern and northeastern Brazil.
      Swainsonine concentrations were detected at concentrations that could potentially
      poison an animal throughout the year although there was some variation between
      months. At one location swainsonine concentrations were generally the highest
      during the rainy season or the months immediately following the rainy season.
      Total calystegine concentrations were similar to those reported previously while
      crude protein concentrations were similar to those found in other Ipomoea species
      and are such that they may explain why I. carnea becomes desirable to grazing
      livestock as forage becomes limited during the dry season. 

PMID- 25572339
TI  - Protective effect of melatonin against myocardial injury induced by epinephrine.
AB  - Epinephrine, in high doses, exhibits cardiotoxicity that is associated with
      excessive production of free radicals. Melatonin is antioxidant and free radical
      scavenger with cardioprotective properties. In our study, cardioprotective
      effects of melatonin against epinephrine cardiotoxicity were explored in the
      model of isolated rat heart. In the melatonin group, melatonin (50 MUmol/l) was
      present in the perfusion solution during the whole experiment. In the control
      group, perfusion solution contained no melatonin. In both of the groups, after 30
      min of initial perfusion, epinephrine was applied during 2 min directly into the
      heart and led to its strong stimulation. Changes in the heart function and
      arrhythmogenesis were evaluated before application of epinephrine and after the
      decline of its acute effects. No significant differences were observed during the
      initial perfusion. However, in the 15th and 20th minute after epinephrine
      application, indexes of ventricular contraction and relaxation were significantly
      higher in the melatonin group. Likewise, the values of the left ventricular
      developed pressure were significantly increased in this group in the 15th minute.
      These differences indicate better preservation of contraction and relaxation in
      the melatonin-treated group. Parameters of arrhythmogenesis-arrhythmia score,
      incidence and total duration of severe ventricular arrhythmias, were not
      significantly different between the experimental groups. However, their markedly
      lower average values in the melatonin-treated group suggest the reduction of
      electrical instability by melatonin. In conclusion, the obtained data confirm
      cardioprotective properties of melatonin and fill in the mosaic of information
      that can lead to the usage of melatonin as a therapeutic tool.

PMID- 25572341
TI  - Interspecific competition between two generalist parasitoids that attack the
      leafroller Epiphyas postvittana (Lepidoptera: Tortricidae).
AB  - Two generalist parasitoids, Dolichogenidea tasmanica (Cameron) (Hymenoptera:
      Braconidae) and Therophilus unimaculatus (Turner) (Hymenoptera: Braconidae)
      attack early instars of tortricid moths, including the light brown apple moth,
      Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae). The two parasitoids co
      exist in natural habitats, while D. tasmanica is dominant in vineyards, whereas
      T. unimaculatus occurs mainly in adjacent native vegetation. This difference
      suggests possible competition between the two species, mediated by habitat. Here,
      we report on the extent of interspecific differences in host discrimination and
      the outcome of interspecific competition between the two parasitoids. The
      parasitoids did not show different behavioural responses to un-parasitized hosts
      or those that were parasitized by the other species. Larvae of D. tasmanica out
      competed those of T. unimaculatus, irrespective of the order or interval between
      attacks by the two species. The host larvae that were attacked by two parasitoids
      died more frequently before a parasitoid completed its larval development than
      those that were attacked by a single parasitoid. Dissection of host larvae
      parasitized by both species indicated that first instars of D. tasmanica attacked
      and killed larval T. unimaculatus. 

PMID- 25572340
TI  - Glitazones inhibit human monoamine oxidase but their anti-inflammatory actions
      are not mediated by VAP-1/semicarbazide-sensitive amine oxidase inhibition.
AB  - Glitazones are peroxisome proliferator-activated receptor gamma (PPARgamma)
      agonists widely used as antidiabetic drugs also known as thiazolidinediones. Most
      of them exert other effects such as anti-inflammatory actions via mechanisms
      supposed to be independent from PPARgamma activation (e.g., decreased plasma
      monocyte chemoattractant protein-1 (MCP-1) levels). Recently, pioglitazone has
      been shown to inhibit the B form of monoamine oxidase (MAO) in mouse, while
      rosiglitazone and troglitazone were described as non-covalent inhibitors of both
      human MAO A and MAO B. Since molecules interacting with MAO might also inhibit
      semicarbazide-sensitive amine oxidase (SSAO), known as vascular adhesion protein
      1 (VAP-1), and since VAP-1/SSAO inhibitors exhibit anti-inflammatory activity,
      our aim was to elucidate whether VAP-1/SSAO inhibition could be a mechanism
      involved in the anti-inflammatory behaviour of glitazones. To this aim, MAO and
      SSAO activities were measured in human subcutaneous adipose tissue biopsies
      obtained from overweight women undergoing plastic surgery. The production of
      hydrogen peroxide, an end-product of amine oxidase activity, was determined in
      tissue homogenates using a fluorometric method. The oxidation of 1 mM tyramine
      was inhibited by pargyline and almost resistant to semicarbazide, therefore
      predominantly MAO-dependent. Rosiglitazone was more potent than pioglitazone in
      inhibiting tyramine oxidation. By contrast, benzylamine oxidation was only
      abolished by semicarbazide: hence SSAO-mediated. Pioglitazone hampered SSAO
      activity only when tested at 1 mM while rosiglitazone was inefficient. However,
      rosiglitazone exhibited anti-inflammatory activity in human adipocytes by
      limiting MCP-1 expression. Our observations rule out any involvement of VAP
      1/SSAO inhibition and subsequent limitation of leukocyte extravasation in the
      anti-inflammatory action of glitazones. 

PMID- 25572342
TI  - N-acetylglucosaminyltransferase V exacerbates concanavalin A-induced hepatitis in
      mice.
AB  - N-Acetylglucosaminyltransferase V (GnT-V) catalyzes beta1-6 branching in
      asparagine-linked oligosaccharides and is one of the most important
      glycosyltransferases involved in carcinogenesis, cancer metastasis and immunity.
      To investigate the biological functions of GnT-V, the present study developed GnT
      V transgenic (Tg) mice and the role of GnT-V in experimental immune-mediated
      hepatitis, induced by concanavalin A (ConA), were investigated. It was found that
      the aberrant expression of GnT-V exacerbated ConA-induced hepatitis in the Tg
      mice compared with the wild-type (WT) mice. The survival rate of the ConA-induced
      hepatitis at a high-dose of ConA was significantly lower in the Tg mice.
      Intravenously injected ConA is known to initially bind predominantly to the
      mannose gland of the liver sinusoidal endothelial cell (LSEC) surface and to
      leads to the activation of various immune cells. In the present study, the
      binding affinity of ConA to the LSECs did not differ between the WT and Tg mice.
      In addition, T cell receptor stimulation by anti-cluster of differentiation
      (CD)3/CD28 antibodies produced lower levels of T helper (Th)1 cytokine
      (interferon-gamma) and higher levels of Th2 cytokine (interleukin-10) in the Tg
      mouse splenic lymphocytes compared with WT mice. The composition of the hepatic
      mononuclear cells revealed that CD11b-positive cells were significantly increased
      in the GnT-V Tg mice. In addition, F4/80-positive cells were significantly
      increased in the Tg mouse liver and the depletion of macrophages reduced the
      difference in the severity of ConA-induced hepatitis between the WT and Tg mice.
      In conclusion, the present findings indicated that the aberrant expression of GnT
      V led to an increase in hepatic macrophage infiltration and enhanced ConA-induced
      hepatitis. Modulation of glycosylation may be a novel therapeutic target for
      immunity-associated acute hepatitis.

PMID- 25572343
TI  - Mediastinal vagus nerve scwhannoma succesfully treated by a biportal VATS
      approach.

PMID- 25572344
TI  - Intensive local thermotherapy cleared extensive viral warts in a patient with
      systemic lupus erythematosus.
AB  - PURPOSE: A variety of medications and procedures are available for the treatment
      of warts, but it appeared the treatment response in systemic lupus erythematosus
      (SLE) patients is poor. It is necessary to investigate the feasibility, safety
      and efficacy of local thermotherapy for extensive viral warts. MATERIALS AND
      METHODS: A SLE patient on systemic steroid developed extensive viral warts on
      both her hands and feet for months. She had a high score of SLE Disease Activity
      Index (SLEDAI), up to 30, and was extensively treated with high and prolonged
      dosage of corticosteroid and intermittent use of cyclophosphamide. We applied
      local hyperthermia at 44  degrees C on a target lesion for 30 min on days 1, 2,
      3, 17, 18, a protocol which has been successfully used in treating viral warts.
      There was no sign of clinical response in a 3-month follow-up. Then we treated
      the patient on a once-a-week protocol. RESULT: All the lesions cleared in ten
      weeks and there was no sign of recurrence. CONCLUSION: This observation suggests
      that more intensive local hyperthermia is required for clearing viral warts in
      SLE.

PMID- 25572345
TI  - Psychedelic symptoms of cannabis and cocaine use as a function of trait
      impulsivity.
AB  - Trait impulsivity has been linked to addiction in humans. It has been suggested
      that drug users with high trait impulsivity levels are more sensitive to
      subjective drug intoxication. This study assessed whether subjective response to
      drugs differs between drug users with normal or high levels of trait impulsivity.
      Regular drug users (N = 122) received doses of cocaine HCl, cannabis, and placebo
      in a three-way crossover study. Their mood, dissociative state, and psychedelic
      symptoms were measured with subjective rating scales (CADDS, Bowdle, POMS). Trait
      impulsivity was assessed with the Barratt Impulsiveness Scale. Cannabis increased
      dissociation and psychedelic state, as well as fatigue, confusion, depression and
      anxiety, and decreased arousal, positive mood, vigor, friendliness, and elation.
      Cocaine increased dissociation, psychedelic state, vigor, friendliness, elation,
      positive mood, anxiety and arousal, while decreasing fatigue. Only a few
      subjective items revealed a drug * trait impulsivity interaction, suggesting that
      psychedelic symptoms were most intense in high impulsivity subjects. Trait
      impulsiveness ratings were negatively correlated with ratings of vigor (r = 
      .197) and positively correlated with ratings of loss of thought control (r =
      .237) during cannabis intoxication. It is concluded that a broad association
      between trait impulsivity and psychedelic subjective drug experience appears to
      be absent. 

PMID- 25572346
TI  - Increased risk of nephrotoxicity: Side effect of colistin use in paediatric
      patients.

PMID- 25572347
TI  - Salvia miltiorrhiza prevents deep vein thrombosis via antioxidative effects in
      endothelial cells.
AB  - Deep vein thrombosis (DVT) is a common clinical problem, which represents a
      significant clinical and economic burden. The present study investigated whether
      Salvia miltiorrhiza (S. miltiorrhiza) could prevent DVT. A total of 30 rabbits
      were randomly divided into three groups (n=10 per group): The control, model and
      Salvia groups. A ligation model was used, where the femoral veins of rabbits were
      exposed and ligated. Measurements of coagulation function, blood rheological
      parameters, antioxidative function and effects on endothelial cells were
      conducted. Treatment with S. miltiorrhiza one week prior to generation of the
      ligation model did not affect the coagulation function much, except to increase
      the prothrombin time. There was a statistically significant difference (P<0.05)
      in whole blood viscosity (1/s, 5/s, 30/s) on the third and seventh days (1/s,
      5/s, 30/s and 200/s) following generation of the model. S. miltiorrhiza exhibited
      promising antioxidative effects, as demonstrated by a significant decrease in
      malondialdehyde content (P<0.05), and an increase in the activities of superoxide
      dismutase (P<0.05), as compared with the model group. S. miltiorrhiza was also
      shown to protect the vascular endothelial cells, as compared with the model
      group. These results suggest that S. miltiorrhiza may have potential applications
      for the treatment of DVT.

PMID- 25572348
TI  - Binocular visual training to promote recovery from monocular deprivation.
AB  - Abnormal early visual experience often leads to poor vision, a condition called
      amblyopia. Two recent approaches to treating amblyopia include binocular
      therapies and intensive visual training. These reflect the emerging view that
      amblyopia is a binocular deficit caused by increased neural noise and poor signal
      in-noise integration. Most perceptual learning studies have used monocular
      training; however, a recent study has shown that binocular training is effective
      for improving acuity in adult human amblyopes. We used an animal model of
      amblyopia, based on monocular deprivation, to compare the effect of binocular
      training either during or after the critical period for ocular dominance
      plasticity (early binocular training vs. late binocular training). We used a high
      contrast, orientation-in-noise stimulus to drive the visual cortex because
      neurophysiological findings suggest that binocular training may allow the
      nondeprived eye to teach the deprived eye's circuits to function. We found that
      both early and late binocular training promoted good visual recovery.
      Surprisingly, we found that monocular deprivation caused a permanent deficit in
      the vision of both eyes, which became evident only as a sleeper effect following
      many weeks of visual training. 

PMID- 25572349
TI  - Radial bias for orientation and direction of motion modulates access to visual
      awareness during continuous flash suppression.
AB  - Two types of radial bias have been demonstrated in the primate visual cortex: for
      orientation and for direction of motion. Considering that a visual neuron's
      directional selectivity is generally perpendicular to its preferred orientation,
      it is counterintuitive that radial biases for orientation and direction of motion
      coexist in retinotopic cortex including primary visual cortex. The current study
      measured the influence of radial bias for orientation and direction of motion on
      the access to visual awareness during continuous flash suppression. Strength of
      static and moving target stimuli, inferred by time to breakup of suppression, was
      modulated by the orientation and motion direction of the suppressed target
      stimulus according to its spatial location, indicating radial biases for both
      orientation and motion direction. However, orientation dominated over direction
      of motion when they were perpendicular to each other. These results indicate
      that, first, orientation-specific neural responses may be stronger than direction
      specific neural responses at the stage of visual processing where interocular
      suppression is resolved. Second, the preferential processing of both orientation
      and direction of motion may result from anisotropic distribution of orientation-
      and direction-selective cells. Third, the neural substrate of the radial
      direction bias may reflect an orientation-specific neural response induced by
      fast-moving random dot patterns. 

PMID- 25572350
TI  - Substitution and pooling in visual crowding induced by similar and dissimilar
      distractors.
AB  - Visual crowding refers to a phenomenon whereby objects that appear in the
      periphery of the visual field are more difficult to identify when embedded within
      clutter. Pooling models assert that crowding results from an obligatory averaging
      or other combination of target and distractor features that occurs prior to
      awareness. One well-known manifestation of pooling is feature averaging, with
      which the features of target and nontarget stimuli are combined at an early stage
      of visual processing. Conversely, substitution models assert that crowding
      results from binding a target and nearby distractors to incorrect spatial
      locations. Recent evidence suggests that substitution predominates when target
      flanker feature similarity is low, but it is unclear whether averaging or
      substitution best explains crowding when similarity is high. Here, we examined
      participants' orientation report errors for targets crowded by similar or
      dissimilar flankers. In two experiments, we found evidence inconsistent with
      feature averaging regardless of target-flanker similarity. However, the observed
      data could be accommodated by a probabilistic substitution model in which
      participants occasionally "swap" a target for a distractor. Thus, we conclude
      that-at least for the displays used here-crowding likely results from a
      probabilistic substitution of targets and distractors, regardless of target
      distractor feature similarity. 

PMID- 25572351
TI  - Impact of temporary hyperthermia on corneal endothelial cell survival during
      organ culture preservation.
AB  - To evaluate temporary exposure to hyperthermia for its impact on endothelial cell
      density of porcine corneas in organ culture medium containing dextran with
      regards to possible negative influences of high temperatures during the storage
      and transport of corneal grafts. Four groups of central discs (diameter 8 mm)
      from the corneas of both eyes in 40 pigs were first organ-cultured (MEM with 6%
      dextran 500) for 24 h at 32 degrees C. Ten corneas were then exposed to 40
      degrees C in group 1, to 42 degrees C in group 2, to 44 degrees C in group 3, and
      to 50 degrees C in group 4 for 12 h each. The paired corneal discs for all groups
      were not treated, stored at 32 degrees C and served as controls. After further
      organ culture of all corneas for 48 h at 32 degrees C to allow regenerative
      processes, corneal endothelium was stained with Alizarin Red S and examined by
      light microscopy. The endothelial cell densities were determined on three central
      images using a system for the automatic estimation of morphometric parameters of
      corneal endothelium. Exposure for 12 h to 40 degrees C as well as to 42 degrees C
      induced no endothelial cell loss. Statistical analysis showed no significant
      difference of the endothelial cell density between corneas exposed to 40 degrees
      C and 42 degrees C and the control corneas (40 degrees C treatment: 4736 +/- 426
      cells/mm(2) and control: 4762 +/- 344 cells/mm(2), p = 0.74; 42 degrees C
      treatment: 4240 +/- 363 cells/mm(2) and control: 4176 +/- 448 cells/mm(2), p =
      0.40). Exposure to 44 degrees C and 50 degrees C lead to total necrosis of the
      endothelial cell layer. Exposure of organ cultured porcine corneas in dextran
      containing medium up to 42 degrees C for 12 h does not compromise the endothelial
      cell density in a clinically relevant manner. Temperatures above 42 degrees C, as
      it might be the case during transports from the cornea bank to the ophthalmic
      surgeon, must be strictly avoided as they damage the endothelial cell layer.

PMID- 25572353
TI  - Venous oxygen saturation is reduced and variable in central retinal vein
      occlusion.

PMID- 25572352
TI  - Clinicopathologic features of orbital immunoglobulin G4-related disease (IgG4
      RD): a case series and literature review.
AB  - BACKGROUND: Involvement of orbital structures by immunoglobulin G4-related
      disease (IgG4-RD) is not uncommon. We conducted this study to evaluate the
      clinicopathologic features of orbital IgG4-RD. MATERIAL/METHODS: This was a
      retrospective, clinicopathologic study. Clinical records, light microscopic
      features, results of immunostaining with IgG & IgG4 and laboratory findings were
      reviewed in 16 patients diagnosed with orbital IgG4-RD. RESULTS: Eleven patients
      had a bilateral disease, and the lacrimal gland was involved in 14. Dense
      sclerosis, plasma cell aggregates and dense lymphoplasmacytic infiltrate were
      seen in all patients. Serum IgG4 titre was elevated in 12 patients. Nine patients
      responded completely to glucocorticoid treatment. Five patients had a relapse on
      discontinuation of treatment. CONCLUSION: Orbital IgG4-RD is a distinct
      clinicopathologic entity requiring increased awareness and needs to be
      differentiated from other orbital lymphoproliferative lesions.

PMID- 25572354
TI  - Egress of large quantities of heavy liquids from exposed choroid: a route for
      possible tumor dissemination via vortex veins in endoresection of choroidal
      melanoma.

PMID- 25572355
TI  - Phacodyne versus VisionBlue as vital dyes in Descemet membrane endothelial
      keratoplasty.

PMID- 25572356
TI  - The effects of ocular magnification on Spectralis spectral domain optical
      coherence tomography scan length.
AB  - PURPOSE: The purpose of this study was to assess the effects of incorporating
      individual ocular biometry measures of corneal curvature, refractive error, and
      axial length on scan length obtained using Spectralis spectral domain optical
      coherence tomography (SD-OCT). METHODS: Two SD-OCT scans were acquired for 50
      eyes of 50 healthy participants, first using the Spectralis default keratometry
      (K) setting followed by incorporating individual mean-K values. Resulting scan
      lengths were compared to predicted scan lengths produced by image simulation
      software, based on individual ocular biometry measures including axial length.
      RESULTS: Axial length varied from 21.41 to 29.04 mm. Spectralis SD-OCT scan
      lengths obtained with default-K ranged from 5.7 to 7.3 mm, and with mean-K from
      5.6 to 7.6 mm. We report a stronger correlation of simulated scan lengths
      incorporating the subject's mean-K value (rho = 0.926, P < 0.0005) compared to
      Spectralis default settings (rho = 0.663, P < 0.0005). CONCLUSIONS: Ocular
      magnification appears to be better accounted for when individual mean-K values
      are incorporated into Spectralis SD-OCT scan acquisition versus using the
      device's default-K setting. This must be considered when taking area measurements
      and lateral measurements parallel to the retinal surface.

PMID- 25572358
TI  - Comment on Eliasdottir et al., Venous oxygen saturation is reduced and variable
      in central retinal vein occlusion.

PMID- 25572359
TI  - Near-infrared spectroscopy and hydrogen clearance: is there any difference
      between these two methods of muscle blood volume estimation?

PMID- 25572357
TI  - Ocular findings in Sheehan's syndrome.
AB  - BACKGROUND: Sheehan's syndrome (SS) is one of the most common causes of
      hypopituitarism. The primary effect of SS is a deficiency in production of growth
      hormone (GH). A number of studies have supported the association between
      congenital GH deficiency and ocular anomalies. However, ocular findings such as
      central corneal thickness (CCT), intraocular pressure (IOP), and retinal nerve
      fiber layer thickness (RNFLT) have not been evaluated in patients with adult GH
      deficiency. The objective of this study was to evaluate ocular anomalies in SS
      with GH deficiency under a cross-sectional design. METHODS: Thirty three SS
      patients with GH deficiency and 28 controls with no history of thyroid, adrenal,
      or pituitary gland diseases or surgery underwent complete hormonal and
      ophthalmological evaluation, including an assessment of CCTs, IOPs, and RNFLT.
      RESULTS: The mean CCTs were significantly lower in the SS group compared with the
      control group (p < 0.001). There was no significant difference between patients
      and controls in terms of mean IOP, mean corrected IOP, and mean RNFLT (p = 0.517,
      p = 0.186, p = 0.965, respectively). The mean CCT was positively correlated with
      insulin-like growth factor 1 (IGF-1; p < 0.01) and adrenocorticotropic hormone
      (ACTH; p < 0.01) and negatively correlated with the corrected mean IOP (p <
      0.05). In covariance analysis, IGF-1 was found to be a potential predictor of the
      mean CCT (p = 0.023). CONCLUSIONS: This study is the first investigation of
      ocular findings in SS and adult GH deficiency. Adult GH deficiency is
      characterized by lower CCT values.

PMID- 25572361
TI  - Mechanically stable, hierarchically porous Cu3(btc)2 (HKUST-1) monoliths via
      direct conversion of copper(II) hydroxide-based monoliths.
AB  - The synthesis of highly crystalline macro-meso-microporous monolithic Cu3(btc)2
      (HKUST-1; btc(3-) = benzene-1,3,5-tricarboxylate) is demonstrated by direct
      conversion of Cu(OH)2-based monoliths while preserving the characteristic
      macroporous structure. The high mechanical strength of the monoliths is promising
      for possible applications to continuous flow reactors. 

PMID- 25572360
TI  - Fucoidan promotes osteoblast differentiation via JNK- and ERK-dependent BMP2-Smad
      1/5/8 signaling in human mesenchymal stem cells.
AB  - Fucoidan has attracted attention as a potential drug because of its biological
      activities, which include osteogenesis. However, the molecular mechanisms
      involved in the osteogenic activity of fucoidan in human alveolar bone marrow
      derived mesenchymal stem cells (hABM-MSCs) remain largely unknown. We
      investigated the action of fucoidan on osteoblast differentiation in hABM-MSCs
      and its impact on signaling pathways. Its effect on proliferation was determined
      using the crystal violet staining assay. Osteoblast differentiation was evaluated
      based on alkaline phosphatase (ALP) activity and the mRNA expression of multiple
      osteoblast markers. Calcium accumulation was determined by Alizarin red S
      staining. We found that fucoidan induced hABM-MSC proliferation. It also
      significantly increased ALP activity, calcium accumulation and the expression of
      osteoblast-specific genes, such as ALP, runt-related transcription factor 2, type
      I collagen-alpha 1 and osteocalcin. Moreover, fucoidan induced the expression of
      bone morphogenetic protein 2 (BMP2) and stimulated the activation of
      extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK) and p38
      mitogen-activated protein kinase by increasing phosphorylation. However, the
      effect of fucoidan on osteogenic differentiation was inhibited by specific
      inhibitors of ERK (PD98059) and JNK (SP600125) but not p38 (SB203580). Fucoidan
      enhanced BMP2 expression and Smad 1/5/8, ERK and JNK phosphorylation. Moreover,
      the effect of fucoidan on osteoblast differentiation was diminished by BMP2
      knockdown. These results indicate that fucoidan induces osteoblast
      differentiation through BMP2-Smad 1/5/8 signaling by activating ERK and JNK,
      elucidating the molecular basis of the osteogenic effects of fucoidan in hABM
      MSCs. 

PMID- 25572362
TI  - Endostar in combination with modified FOLFOX6 as an initial therapy in advanced
      colorectal cancer patients: a phase I clinical trial.
AB  - PURPOSE: Endostar is a recombinant human endostatin with antiangiogenic
      properties that has been useful in treating a wide range of cancers and shows
      promise for use in combination treatment for advanced colorectal cancer. This
      study aimed to evaluate the drug safety and tolerability of continuous
      intravenous infusion (CIV) of endostar in combination with modified FOLFOX6
      (mFOLFOX6) as an initial therapy in advanced colorectal cancer patients. METHODS:
      This was a single-center, single-arm, open, dose-escalation study in patients
      with advanced colorectal cancer at Fudan University Shanghai Cancer Center
      between August 2010 and January 2012. A total of 21 patients were included.
      Standard dosage of mFOLFOX6 was used. CIV endostar commenced on day 4 to day 14
      ascending from 7.5 to 15, 30, 45, 60, and 75 mg/m(2)/day. Primary outcomes were
      dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of CIV endostar in
      combination with mFOLFOX6. Secondary outcomes were pharmacokinetic parameters.
      Physical examination, performance status, standard blood tests and
      electrocardiograms were performed. RESULTS: MTD was 75 mg/m(2)/day. Adverse
      events included leucopenia (n = 17, 81 %), neutropenia (n = 12, 57.1 %), anemia
      (n = 5, 23.8 %), anorexia (n = 6, 28.6 %) and constipation (n = 4, 19.0 %). One
      patient with an allergic reaction stopped chemotherapy. Two patients stopped
      endostar treatment, one with level 3 ventricular premature beat (DLT at 15
      mg/m(2)/day) and one with a level 1 ventricular arrhythmia (30 mg/m(2)/day). The
      main ECG changes were ST-segment and T wave changes. Exposure to endostar and CIV
      dose was linear between 7.5 and 30 mg/m(2)/day (R (2) = 0.974). CONCLUSIONS:
      Endostar in combination with mFOLFOX6 was generally safe and well tolerated.

PMID- 25572363
TI  - Regulatory role of Lactobacillus acidophilus on inflammation and gastric
      dysmotility in intestinal mucositis induced by 5-fluorouracil in mice.
AB  - PURPOSE: Lactobacillus acidophilus is widely used for gastrointestinal disorders,
      but its role in inflammatory conditions like in chemotherapy-induced mucositis is
      unclear. Here, we report the effect of L. acidophilus on 5-fluorouracil-induced
      (5-FU) intestinal mucositis in mice. METHODS: Mice weighing 25-30 g (n = 8) were
      separated into three groups, saline, 5-FU, and 5-FU + L. acidophilus (5-FU-La)
      (16 * 10(9) CFU/kg). In the 5-FU-La group, L. acidophilus was administered
      concomitantly with 5-FU on the first day and alone for two additional days. Three
      days after the last administration of L. acidophilus, the animals were euthanized
      and the jejunum and ileum were removed for histopathological assessment and for
      evaluation of levels of myeloperoxidase activity, sulfhydryl groups, nitrite, and
      cytokines (TNF-alpha, IL-1beta, CXCL-1, and IL-10). In addition, we investigated
      gastric emptying using spectrophotometry after feeding a 1.5-ml test meal by
      gavage and euthanasia. Data were submitted to ANOVA and Bonferroni's test, with
      the level of significance at p < 0.05. RESULTS: Intestinal mucositis induced by 5
      FU significantly (p < 0.05) reduced the villus height-crypt depth ratio and GSH
      concentration and increased myeloperoxidase activity and the nitrite
      concentrations compared with the control group. Furthermore, 5-FU significantly
      (p < 0.05) increased cytokine (TNF-alpha, IL-1beta, and CXCL-1) concentrations
      and decreased IL-10 concentrations compared with the control group. 5-FU also
      significantly (p < 0.05) delayed gastric emptying and gastrointestinal transit
      compared with the control group. All of these changes were significantly (p <
      0.05) reversed by treatment with L. acidophilus. CONCLUSIONS: Lactobacillus
      acidophilus improves the inflammatory and functional aspects of intestinal
      mucositis induced by 5-FU.

PMID- 25572364
TI  - Dental conferences: an enigma.

PMID- 25572365
TI  - Early orthopedic correction of skeletal Class III malocclusion using combined
      reverse twin block and face mask therapy.
AB  - A 6-year 8-month-old girl presented with a moderate Class III malocclusion
      characterized by mid-face deficiency and an anterior cross bite. In the first
      phase, the patient was treated with combination of reverse twin block and
      facemask therapy. In phase two, fixed appliances were placed in the permanent
      dentition. The post treatment results were good and a favorable growth tendency
      could be observed. The correction of the Class III malocclusion occurred by a
      combination of skeletal and dental improvements. This report shows successful
      correction of skeletal Class III malocclusion in the early transitional dentition
      using combination therapy. 

PMID- 25572366
TI  - Evaluation of cavitated and non-cavitated carious lesions using the WHO basic
      methods, ICDAS-II and laser fluorescence measurements.
AB  - AIM: This study was aimed to compare the diagnostic outcome of the WHO criteria,
      ICDAS-II criteria and laser fluorescence measurements in measuring the caries
      ratings of children. SETTINGS AND DESIGN: Cross-sectional study. MATERIALS AND
      METHODS: The study involved 31 children between 3 and 14 years of age, attending
      the Department of Pedodontics at Maulana Azad College of Dental Sciences, New
      Delhi. The surface-related caries status was registered according to the WHO
      basic method criteria (1997). Additionally, the ICDAS-II visual criteria and the
      DIAGNOdent readings were documented. STATISTICAL ANALYSIS USED: The data were
      analysed with ezANOVA and Excel 2000 (Microsoft Corporation, Redmond, WA, USA).
      RESULTS: The mean ICDAS-II values amounted to 8.76 +/- 0.72. The mean values for
      DMFS/def were 7.67 +/- 0.91, whereas for DIAGNOdent it amounted to 4.00 +/- 0.62.
      CONCLUSIONS: In conclusion, this study showed the diagnostic potential of the
      ICDAS-II criteria in comparison to the traditional WHO criteria by means of the
      non-cavitated caries lesions additionally detected. The DIAGNOdent use in field
      studies that already apply detailed visual criteria seems to bring limited
      additional information.

PMID- 25572367
TI  - Correlation between dental anxiety, Sense of Coherence (SOC) and dental caries in
      school children from Bangalore North: a cross-sectional study.
AB  - BACKGROUND: Very few publications report on the relationship between
      'salutogenesis', as measured by the concept of Sense of Coherence (SOC), and
      generally speaking an individual's overall oral health- related quality of life
      (OHRQL). To add to this, there is even lesser information regarding the
      behavioral aspect of dental anxiety. AIM: The aim of the present study was to
      evaluate the relationship between dental anxiety, SOC and dental caries in school
      children from Bangalore North. MATERIALS AND METHODS: The study had a sample of
      529 children from various schools, age between 12-16 in Bangalore north. The
      study comprised of 17 questions which were handed over to them; and upon receival
      of the questionnaire the respective decayed, missing, filled tooth surfaces index
      (DMFS) score was checked which was then compared with dental anxiety and SOC.
      STATISTICAL ANALYSIS USED: One way analysis of variance (ANOVA) F-test and
      multiple comparison procedures (MCPs). RESULT: High dental anxiety predicted high
      dental caries index and low SOC predicted high dental caries index in association
      with advancing children's age from 12-16 years. CONCLUSION: Dental anxiety had a
      direct relationship with dental caries and SOC had an inverse relationship with
      dental caries.

PMID- 25572369
TI  - Assessment of traumatic dental injuries in patients with cerebral palsy.
AB  - BACKGROUND: Cerebral palsy is an umbrella term for a group of conditions
      characterized essentially by motor dysfunctions that may be associated with
      sensory or cognitive impairment. Such children tend to have a higher incidence of
      traumatic dental injuries than the general population. This increased incidence
      is often attributed to poor muscular co-ordination that predisposes individuals
      with Cerebral palsy to trauma Aim: The study was conducted to assess different
      dental injuries and the risk factors for dental trauma to occur in patients with
      cerebral palsy. MATERIALS AND METHODS: The study comprised 70 children and
      adolescents with cerebral palsy attending special school in Durg and Bhilai city
      between 7 and 18 years of age. RESULTS: Dentinal fracture was seen in 40% of
      cases. Few cases had tooth displacement, discoloration, and pulpal involvement.
      CONCLUSION: Dentists should be well aware of the possible dental injuries in such
      patients. Preventive measure measures should be taken by health care provider to
      reduce traumatic exposure.

PMID- 25572368
TI  - Non-nutritive sucking habits after three years of age: a case-control study.
AB  - BACKGROUND: Non-nutritive sucking habits can result in negative consequences on
      the development of orofacial structures and occlusion. AIM: Assess factors
      associated with non-nutritive sucking habits in children after 3 years old.
      MATERIALS AND METHODS: A case-control study was carried out in two stages. In the
      first stage, a cross-sectional study was conducted with 638 children aged 3-6
      years. In the second stage, a case-control study (1:2) was conducted. The case
      group included all children who presented some non-nutritive sucking habits in
      the first stage of the study (n = 110). The control group (n = 220) was made up
      of children who had never presented non-nutritive sucking habits, matched to the
      case group for gender and age. The data were collected during the national
      poliomyelitis vaccination campaign, through a questionnaire applied to
      parents/guardians with questions related to the presence of sucking habits,
      sociodemographic aspects, birth aspects, and early life of the child. Statistical
      analysis involved descriptive analysis, chi-square test, Mann-Whitney test, and
      conditional logistic regression. RESULTS: Reduction in maternal education was a
      protective factor for the development of non-nutritive sucking habits (education
      <=8 years OR = 0.38, CI 95%: 0.16, 0.89, P = 0.025). Prematurity (OR = 3.30, CI
      95%: 1.13, 9.69, P = 0.030) and a longer period using a baby bottle (OR = 1.03,
      CI 95%: 1.01, 1.05, P = 0.006) remained associated with a greater possibility of
      the occurrence of sucking habits, regardless of monthly family income.
      CONCLUSION: Non-nutritive sucking habits were associated with maternal education,
      premature birth, and greater time of bottle feeding in children after 3 years
      old.

PMID- 25572370
TI  - Evaluation of remineralizing potential of commercially available child formula
      dentifrices: an in vitro study.
AB  - AIM: The aim of this in vitro study is to evaluate the remineralizing potential
      of commercially available low fluoride child formula dentifrice on primary teeth.
      MATERIALS AND METHODS: Total 30 primary teeth were placed in demineralizing
      solution for 96 hours to produce artificial carious lesions of approximately 100
      MUm depth, and then cut longitudinally into 30 sections of 100-150 MUm thickness
      and randomly assigned to three groups. Sections were treated with dentifrices
      containing Colgate (r) (anti tooth decay) 500 ppm NaF, Cheerio gel (r) 458 ppm
      MFP and Vicco (r) non-fluoridated dentifrice. Lesions were evaluated using
      polarized light microscopy. RESULTS: Colgate (r) (anti tooth decay) 500 ppm NaF
      sections exhibited a statistically significant decrease in lesion depth (P <
      0.05, paired t-test), whereas those in Cheerio gel (r) 458 ppm MFP showed a
      decrease in lesion depth but was not statistically significant. Vicco (r) non
      fluoridated dentifrice showed increase in lesion depth. STATISTICS: A paired t
      test is used to evaluate pre- and post-treatment lesion depth measurements, and
      Newman-Keuls multiple post hoc procedures was carried out to compare pair-wise
      difference of pre- and post-treatment lesion depth. CONCLUSION: The Colgate (r)
      (anti tooth decay) 500 ppm NaF dentifrice and Cheerio gel (r) 458 ppm MFP
      demonstrated remineralization of carious lesions by virtue of decrease in lesion
      depth, whereas Vicco (r) non-fluoridated dentifrice showed increase in lesion
      depth.

PMID- 25572371
TI  - Pediatric dental chair vs. traditional dental chair: a pediatric dentist's poll.
AB  - OBJECTIVE: Proper positioning of the child patient, can not only have positive
      ramifications for the operator's posture, comfort, and career longevity - it can
      also lead to better treatment and increased productivity. The aim of the survey
      questionnaire was to assess the utilization, need, and attitude concerning dental
      chairs among pediatric dentist while working on and managing the child patient.
      STUDY DESIGN: The questions were structured using adobe forms central online
      software, regarding the user-friendliness of pediatric dental chair vs.
      traditional adult dental chair available in the market. RESULTS: Our result shows
      that out of 337 respondents, 79% worked on pediatric dental chair, whereas 21%
      had no experience of it. Of these 79% pediatric dentist, 48% preferred pediatric
      dental chair. But pediatric dental problem still has certain disadvantages like
      higher cost, leg space problem, lower availability, etc. CONCLUSION: During the
      research it was found that ergonomics and usability issues were the main
      problems. Thus, pediatric dental chair is not so popular in the current scenario.
      This study allowed for general ideas for the improvement of dental chairs and
      thus improved dental chair would fill the gap in the current scenario.

PMID- 25572372
TI  - Shear bond strength evaluation of adhesive and tooth preparation combinations
      used in reattachment of fractured teeth: an ex-vivo study.
AB  - OBJECTIVES: The objectives of this study were to evaluate the bond strengths of
      different adhesive materials, different tooth preparation designs and adhesive
      tooth preparation combinations to reattach fractured incisor fragments. MATERIALS
      AND METHODS: The study sample comprised 48 intact human maxillary central
      incisors divided into two groups A and B. The incisal third was sectioned with a
      diamond disc. The teeth in Group A were reattached with bonding agent and in
      Group B with resin luting cement. The teeth in each Group were further divided
      into three sub-groups based on the preparation designs viz., simple attachment,
      chamfer on labial surface, groove with shoulder on labial surface and restored
      with nano-composite. Shear Bond Strength was calculated by applying load incisal
      to the fracture line. T-test and one-way ANOVA were used to evaluate the bond
      strength between the groups and within the group respectively. RESULTS:
      Reattachment with resin luting cement showed high bond strength compared to
      bonding agent (P < 0.05). Within the subgroups 'groove with shoulder' showed
      better bond strength compared to simple attachment and chamfer and the result was
      statistically significant (P < 0.05). CONCLUSION: Reattachment of fractured
      fragments can be considered as a good alternative treatment option when the
      fragment is available.Reattachment with resin luting cement and the preparation
      design of "groove with shoulder" showed better results.

PMID- 25572373
TI  - Assessment of oral health status of Santal (tribal) children of West Bengal.
AB  - CONTEXT: Santal is the third largest tribal community of India leading a very
      poor standard of education and life style. There are, however, few population
      based studies evaluating the oral health status among Santal children in West
      Bengal. AIMS: The aim of the study was to evaluate the oral health status of
      Santal children of West Bengal by assessing prevalence of dental caries and
      inflammatory condition of gingival. SETTINGS AND DESIGN: Santal children aged
      between 2-14 years (N = 1205) were randomly selected from different Santal
      communities of West Bengal for this study. The children were divided into three
      different groups according to dentition. MATERIALS AND METHODS: Caries for
      permanent dentition Decayed Missing Filled Tooth (DMFT), for deciduous dentition
      decayed extracted filled (def index was used. For mixed dentition DMF and def was
      measured respectively and then added together. Inflammatory condition of gingival
      was assessed by papillary marginal attachment (PMA) index. STATISTICAL ANALYSIS
      USED: the data was analyzed statistically by SPSS software version 11. RESULTS:
      The study showed there was no significant difference (P > 0.05) between the
      average decayed extracted filled teeth (deft)/DMFT for boys and girls in
      deciduous and permanent dentition. But in mixed dentition this value for the boys
      was significantly higher (P < 0.001) than girls. 'Z' values were found to be non
      significant when compared mild, moderate and severe gingivitis between boys and
      girls in each dentition group, but mild gingivitis significantly increases from
      deciduous dentition to mixed to permanent dentition (P <0.001).

PMID- 25572374
TI  - RMS Pictorial Scale (RMS-PS): an innovative scale for the assessment of child's
      dental anxiety.
AB  - BACKGROUND: Dental anxiety assessment for young children is as important as
      performing their treatment. Appropriate knowledge of patient's anxiety boosts
      confidence and will help us to review potential management options specific to
      every child. AIM: This study aimed to validate (RMS) Pictorial Scale (RMS-PS) and
      to compare it with Venham Picture Test (VPT) and Facial image scale (FIS) in
      measuring dental anxiety for young children during their first dental visit.
      MATERIALS AND METHODS: A total of 102 healthy children aged between 4 and 14
      years during their first dental visit were randomly selected for the study.
      Childs anxiety level was measured using three different scales namely (i) RMS-PS
      (ii) VPT, and (iii) FIS. STATISTICAL ANALYSIS: Student t test was used to compare
      the scores obtained from all the three scales. Pearson correlation test was used
      to obtain correlation among the scales used in the study. RESULTS: A strong
      correlation (0.76) was found between the VPT and RMS-PS, and a moderate
      correlation (0.5) was found between RMS-PS and FIS, indicating good validity for
      the RMS-PS. CONCLUSIONS: The findings of this study suggest that the RMS-PS can
      be a newer and easiest means for the assessment of dental anxiety for young
      children in a clinical context.

PMID- 25572375
TI  - Conservative management of large radicular cysts associated with non-vital
      primary teeth: a case series and literature review.
AB  - Radicular cysts are the most common odontogenic cystic lesions of inflammatory
      origin. Large radicular cyst is comparatively less frequently associated with
      primary teeth. They represent only 0.5-3.3% of the total number of cysts in
      primary dentition. Radicular cysts arising from deciduous teeth are reported to
      occur in age range of 3-19 years with a male predominance. Although large
      radicular cysts are treated by enucleation with extensive removal of bone and
      vital teeth, marsupialization can be preferred as a conservative approach to
      reduce the morbidity. The purpose of this article is to report a case series of
      large radicular cysts associated with badly mutilated and traumatized primary
      teeth and to demonstrate how best they can be conservatively treated during mixed
      dentition period. 

PMID- 25572376
TI  - LEOPARD syndrome: you could be the first one to diagnose!
AB  - Leopard syndrome is a rare genetic disease complex associated with multiple
      anomalies. The main anomalies are summarized in the acronym LEOPARD in which each
      letter corresponds to mnemonic for the major features of this disorder:multiple
      Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic
      stenosis, Abnormal genitalia, Retardation of growth, and sensory neural Deafness.
      A Four year old male patient reported with the chief complaint of decayed
      anterior tooth without any relevant past medical history. Based on the clinical
      features; the child was subjected to genetic and general physical appraisal which
      helped in identifying Leopard syndrome. A multidisciplinary approach by the
      pedodontist and medical consultants aided in the identification and management of
      this rare syndrome. LEOPARD syndrome has been rarely reported in the diseases
      associated with oro-dental or craniofacial anomalies. In this case report we
      describe these anomalies and discuss the relationship between them and the
      proposed etiology of the disease. 

PMID- 25572377
TI  - Bilateral deep neck space infection in pediatric patients: review of literature
      and report of a case.
AB  - The diagnosis and treatment of deep neck infections is still an enigma for
      surgeons and physicians. Because of the complexity and the deep location of this
      region, the diagnosis and treatment in this area is difficult. The anatomy of
      deep neck spaces is highly complex and therefore precise localization of
      infections in this region is very difficult. The diagnoses of deep neck space
      infection (DNSI) are difficult because of the deep location of these spaces and
      are usually covered by substantial amount of normal superficial soft tissue.
      Access: To gain surgical access to the deep neck spaces, the superficial tissues
      must be crossed with the risk of injury to the neurovascular structures in the
      neck. Neural dysfunction, vascular erosion or thrombosis, and osteomyelitis are
      some of the complications of DNSI because of the proximity of nerves, vessels,
      bones, and other soft tissues. Deep neck spaces are communicated with each other
      and infections from one space can spread to adjacent space. DNSI, if not
      diagnosed early and promptly, may result in serious consequences even mortality.
      The treatment of DNSI with antibiotic therapy and drainage is most often
      definitive and recurrence of these cases is rare. 

PMID- 25572378
TI  - Hunter's syndrome: a case report.
AB  - Hunter's syndrome or mucopolysaccharidosis (MPS) type II is an X-linked recessive
      mucopolysaccharide disorder caused by a defect in the metabolism of
      glycosaminoglycans (GAGs) characterized by involvement of nervous,
      cardiovascular, respiratory, and mucoskeletal systems along with numerous oral
      manifestations. This is a case report of a 13-year-old boy referred to the
      Department of Pediatric Dentistry with a chief complaint of irregularly placed
      teeth from a general physician. Here we highlight the pivotal role of pediatric
      dentists in diagnosis and treatment planning for patients diagnosed with such
      systemic conditions and the provision of advanced dental care in the management
      of the same.

PMID- 25572379
TI  - Management of an endo-perio lesion in an immature tooth using autologous platelet
      rich fibrin: a case report.
AB  - Treatment of an endo-perio lesion involving a non-vital young permanent tooth is
      a highly challenging task to Pediatric Dentists. There is a quest for the newer
      biological approach to management of these lesions as traditional methods have
      various disadvantages. Recently, platelet-rich fibrin (PRF), a second-generation
      platelet concentrate, is rich in growth factors have been used in the periodontal
      regeneration procedure. The purpose of this paper is to describe the efficacy of
      PRF in the treatment of a deep intra bony defect associated with an endo-perio
      lesion in an immature right mandibular first premolar of 12-year-old female
      patient. A freshly prepared autologous PRF membrane was placed in the bony defect
      following debridement. Clinical and radiographic follow-up were performed at
      regular intervals that revealed absence of pain, gain in clinical attachment
      level, reduction in probing depth, and excellent bone regeneration indicating
      successful outcome.

PMID- 25572380
TI  - Bloch Sulzberger syndrome (Incontinentia Pigmenti): a rare case report with
      dental defects.
AB  - Incontinentia Pigmenti (IP) is a multisystem genodermatosis characterized by
      cutaneous, neurologic, ophthalmologic, and dental abnormalities. This article
      reports the clinical features and management of a 4-year-old girl diagnosed with
      IP. 

PMID- 25572381
TI  - Explaining evolution via constrained persistent perfect phylogeny.
AB  - BACKGROUND: The perfect phylogeny is an often used model in phylogenetics since
      it provides an efficient basic procedure for representing the evolution of
      genomic binary characters in several frameworks, such as for example in haplotype
      inference. The model, which is conceptually the simplest, is based on the
      infinite sites assumption, that is no character can mutate more than once in the
      whole tree. A main open problem regarding the model is finding generalizations
      that retain the computational tractability of the original model but are more
      flexible in modeling biological data when the infinite site assumption is
      violated because of e.g. back mutations. A special case of back mutations that
      has been considered in the study of the evolution of protein domains (where a
      domain is acquired and then lost) is persistency, that is the fact that a
      character is allowed to return back to the ancestral state. In this model
      characters can be gained and lost at most once. In this paper we consider the
      computational problem of explaining binary data by the Persistent Perfect
      Phylogeny model (referred as PPP) and for this purpose we investigate the problem
      of reconstructing an evolution where some constraints are imposed on the paths of
      the tree. RESULTS: We define a natural generalization of the PPP problem obtained
      by requiring that for some pairs (character, species), neither the species nor
      any of its ancestors can have the character. In other words, some characters
      cannot be persistent for some species. This new problem is called Constrained PPP
      (CPPP). Based on a graph formulation of the CPPP problem, we are able to provide
      a polynomial time solution for the CPPP problem for matrices whose conflict graph
      has no edges. Using this result, we develop a parameterized algorithm for solving
      the CPPP problem where the parameter is the number of characters. CONCLUSIONS: A
      preliminary experimental analysis shows that the constrained persistent perfect
      phylogeny model allows to explain efficiently data that do not conform with the
      classical perfect phylogeny model.

PMID- 25572382
TI  - Short pulse laser induces less inflammatory cytokines in the murine retina after
      laser photocoagulation.
AB  - AIMS: The purpose of this study was to evaluate the effect of pulse duration on
      the expression of inflammatory cytokines in the murine retina after laser
      photocoagulation treatment with a PASCAL((r)) pattern scan laser photocoagulator
      and conventional laser treatment. METHODS: Retinal scatter laser photocoagulation
      was performed on C57BL/6J mice using a short pulse (10 ms) with a PASCAL laser or
      conventional settings (100 ms) with a multicolor laser. Eyes were enucleated
      before treatment (control) and 1 day, 3 days and 7 days after treatment. The
      levels of inflammatory cytokines (i.e., VEGF, MCP-1, RANTES and IL-6) in the
      retina/choroid were quantified by an ELISA. The expression patterns of VEGF and
      macrophages (i.e., F4/80) in the retina/choroid were evaluated by
      immunohistochemistry. RESULTS: The levels of RANTES, IL-6 and MCP-1 after PASCAL
      and conventional laser treatments were significantly elevated compared with
      controls (p < 0.05). Conventional laser treatment, but not PASCAL treatment,
      resulted in the up-regulation of VEGF. RANTES and IL-6 levels on day 1 and MCP-1
      levels on day 3 in the sensory retina were also significantly up-regulated with
      conventional laser treatment compared with PASCAL treatment (p < 0.05).
      Immunohistochemical analysis showed that PASCAL treatment was associated with
      lower VEGF and F4/80 expression levels compared with conventional laser
      treatment. CONCLUSIONS: Our data suggested that the short pulse duration induced
      fewer inflammatory cytokines in the sensory retina compared with the conventional
      pulse duration. Short pulse laser photocoagulation with the PASCAL may prevent
      macular edema after panretinal photocoagulation.

PMID- 25572383
TI  - Preload dependence indices to titrate volume expansion during septic shock: a
      randomized controlled trial.
AB  - INTRODUCTION: In septic shock, pulse pressure or cardiac output variation during
      passive leg raising are preload dependence indices reliable at predicting fluid
      responsiveness. Therefore, they may help to identify those patients who need
      intravascular volume expansion, while avoiding unnecessary fluid administration
      in the other patients. However, whether their use improves septic shock prognosis
      remains unknown. The aim of this study was to assess the clinical benefits of
      using preload dependence indices to titrate intravascular fluids during septic
      shock. METHODS: In a single-center randomized controlled trial, 60 septic shock
      patients were allocated to preload dependence indices-guided (preload dependence
      group) or central venous pressure-guided (control group) intravascular volume
      expansion with 30 patients in each group. The primary end point was time to shock
      resolution, defined by vasopressor weaning. RESULTS: There was no significant
      difference in time to shock resolution between groups (median (interquartile
      range) 2.0 (1.2 to 3.1) versus 2.3 (1.4 to 5.6) days in control and preload
      dependence groups, respectively). The daily amount of fluids administered for
      intravascular volume expansion was higher in the control than in the preload
      dependence group (917 (639 to 1,511) versus 383 (211 to 604) mL, P = 0.01), and
      the same held true for red cell transfusions (178 (82 to 304) versus 103 (0 to
      183) mL, P = 0.04). Physiologic variable values did not change over time between
      groups, except for plasma lactate (time over group interaction, P <0.01).
      Mortality was not significantly different between groups (23% in the preload
      dependence group versus 47% in the control group, P = 0.10). Intravascular volume
      expansion was lower in the preload dependence group for patients with lower
      simplified acute physiology score II (SAPS II), and the opposite was found for
      patients in the upper two SAPS II quartiles. The amount of intravascular volume
      expansion did not change across the quartiles of severity in the control group,
      but steadily increased with severity in the preload dependence group.
      CONCLUSIONS: In patients with septic shock, titrating intravascular volume
      expansion with preload dependence indices did not change time to shock
      resolution, but resulted in less daily fluids intake, including red blood cells,
      without worsening patient outcome. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01972828. Registered 11 October 2013.

PMID- 25572385
TI  - Cyberbullying, help-seeking and mental health in young Australians: implications
      for public health.
AB  - OBJECTIVES: To examine the relationship between young Australians' cyberbullying
      experiences, their help-seeking practices and associated mental well-being and
      social connectedness, with a view to informing national health and well-being
      agendas. METHODS: An online survey was administered to young people aged 12-18
      years (n = 2,338), recruited across Australia in year 2 of a larger 4-year study.
      RESULTS: Youth with no experience of cyberbullying had better well-being profiles
      and mental health overall. Conversely, cyberbully victims, had poorer well-being
      and mental health and tended not to engage with online support services, in spite
      of being more likely to be online after 11 pm. Parents and peers were identified
      as key sources of help for most young people when dealing with problems.
      CONCLUSIONS: Cyberbullying is a public health issue particularly for vulnerable
      youth whose mental health and well-being is impacted more than those not
      involved. As youth are spending increasing time in the 24/7 online environment,
      there is a need to develop initiatives that engage young people and encourage
      help-seeking online, whilst concomitantly building capacity of parents and peers
      to support their well-being.

PMID- 25572387
TI  - Thyroid incidentalomas in patients with multiple endocrine neoplasia type 1.
AB  - OBJECTIVE: Currently, little is known about the prevalence of thyroid tumors in
      multiple endocrine neoplasia type 1 (MEN1) patients and it is unclear whether
      tumorigenesis of these thyroid tumors is MEN1-related. The aim of the study was
      to assess the prevalence of thyroid incidentalomas in MEN1 patients compared with
      nonMEN1 patients and to verify whether thyroid tumorigenesis is MEN1-related.
      DESIGN: A cross-sectional study. METHODS: The study included two groups: patients
      with MEN1 and a matched non-MEN1 control group without known thyroid disease, who
      underwent an ultrasound of the neck for the localization of parathyroid adenoma.
      Ninety-five MEN1 patients underwent ultrasound of the neck and were matched on
      gender and age with non-MEN1 patients. The prevalence of thyroid incidentalomas
      described in the ultrasound report was scored. Multinodular goiters, solitary
      nodes, and cysts were scored as incidentalomas. Presence of nuclear menin
      expression was evaluated by menin immunostaining of the thyroid tumors. RESULTS:
      In the MEN1 group, 43 (45%) patients had a thyroid incidentaloma compared with 48
      (51%) in the non-MEN1 group, of which 14 (15%) and 16 (17%), respectively, were
      solitary nodes. Menin was expressed in the nuclei of all evaluated thyroid
      tumors. CONCLUSIONS: MEN1 patients do not have a higher prevalence of thyroid
      incidentalomas compared with primary hyperparathyroidism patients without the
      diagnosis of MEN1. Menin was expressed in the thyroid tumors of MEN1 patients.

PMID- 25572388
TI  - Soluble Klotho and intact fibroblast growth factor 23 in long-term kidney
      transplant patients.
AB  - BACKGROUND: Controversies exist whether disturbances in mineral and bone disorder
      (MBD) normalise or persist after kidney transplantation. We assessed markers of
      MBD in patients with well-functioning kidney transplants to minimise confounding
      by reduced transplant function. METHODS: In this cross-sectional study, 40
      patients aged >=18 years who received a first kidney transplant more than 10
      years ago were included. A well-functioning transplant was defined as an
      estimated glomerular filtration rate (eGFR) >=45 ml/min per 1.73 m(2). RESULTS:
      Median time since transplantation was 18.3 years (inter quartile range (IQR) 12.2
      26.2). Albumin-corrected serum calcium levels were above upper limit of normal in
      15% of the transplanted patients, and serum phosphate levels below lower limit of
      normal in 31%. The median levels of intact parathyroid hormone (iPTH) and intact
      fibroblast growth factor 23 (iFGF23) were significantly higher than that in a
      group of healthy volunteers (11.3 pmol/l (IQR: 8.7-16.2) vs 4.4 pmol/l (IQR: 3.8
      5.9), P<0.001 and 75.0 pg/ml (IQR: 53.3-108.0) vs 51.3 pg/ml (IQR: 36.3-67.6),
      P=0.004 respectively). There was a non-significant reduction in soluble Klotho
      (sKlotho) levels (605 pg/ml (IQR: 506-784) vs 692 pg/ml (IQR: 618-866)). When
      compared with a control group matched for eGFR, levels of iPTH were significantly
      higher (P<0.001), iFGF23 had a non-significant trend towards higher levels and
      sKlotho towards lower levels. CONCLUSIONS: In long-term kidney transplant
      patients with well-functioning kidney transplants, we found inappropriately high
      levels of iPTH and iFGF23 consistent with a state of persistent
      hyperparathyroidism. We speculate that the primary defect, FGF23 resistance, has
      evolved in the parathyroid gland before transplantation, and persists due to long
      half-life of the parathyroid cells.

PMID- 25572389
TI  - Therapy of endocrine disease: response and toxicity of small-molecule tyrosine
      kinase inhibitors in patients with thyroid carcinoma: a systematic review and
      meta-analysis.
AB  - CONTEXT: Many tyrosine kinase inhibitors (TKIs) have been studied in patients
      with thyroid carcinoma (TC). However, the effect and toxicity of various TKIs in
      differentiated TC (DTC) and medullary TC (MTC) patients have not been directly
      compared. The aim of the present systematic review and meta-analysis was to
      systematically summarize response and toxicity of TKIs in TC patients. METHODS:
      All major databases were systematically searched for publications on TKIs in TC.
      Primary endpoint was objective response; secondary endpoints were clinical
      benefit, percentage TKI dose reduction/discontinuation, hand-foot syndrome,
      diarrhea, and nausea/vomiting. Meta-analysis was performed using an exact
      likelihood approach and a logistic regression. Pooled percentages and 95% CIs
      were reported. RESULTS: In total, 22 publications were included. For DTC
      patients, gefitinib induced no objective responses. Pooled percentage was highest
      for pazopanib, 49 (95% CI 33-64)%, and was 17 (95% CI 12-24)% for sorafenib. For
      MTC, gefitinib and imatinib induced no objective responses, whereas sunitinib
      induced objective response in 43 (95% CI 14-77)%. For vandetanib and
      cabozantinib, these numbers were 40 (95% CI 34-46)% and 27 (95% CI 22-32)%
      respectively. Clinical benefit was found in 53 (95% CI 48-59)% of DTC patients on
      sorafenib, and in 84 (95% CI 79-88)% and 55 (95% CI 49-61)% of MTC patients on
      vandetanib and cabozantinib respectively. All TKIs were associated with
      considerable toxicity. CONCLUSION: The currently studied TKIs show a modest
      response, while side effects are not negligible. Therefore, we suggest to solely
      consider TKIs in TC patients with rapid progressive disease, for whom the
      benefits of treatment outweigh toxicity.

PMID- 25572384
TI  - Targeting TRP channels for chronic cough: from bench to bedside.
AB  - Cough is currently the most common reason for patients to visit a primary care
      physician in the UK, yet it remains an unmet medical need. Current therapies have
      limited efficacy or have potentially dangerous side effects. Under normal
      circumstances, cough is a protective reflex to clear the lungs of harmful
      particles; however, in disease, cough can become excessive, dramatically
      impacting patients' lives. In many cases, this condition is linked to
      inflammatory diseases such as asthma and chronic obstructive pulmonary disease
      (COPD), but can also be refractory to treatment and idiopathic in nature.
      Therefore, there is an urgent need to develop therapies, and targeting the
      sensory afferent arm of the reflex which initiates the cough reflex may uncover
      novel therapeutic targets. The cough reflex is initiated following activation of
      ion channels present on vagal sensory afferents. These ion channels include the
      transient receptor potential (TRP) family of cation-selective ion channels which
      act as cellular sensors and respond to changes in the external environment. Many
      direct activators of TRP channels, including arachidonic acid derivatives, a
      lowered airway pH, changes in temperature, and altered airway osmolarity are
      present in the diseased airway where responses to challenge agents which activate
      airway sensory nerve activity are known to be enhanced. Furthermore, the
      expression of some TRP channels is increased in airway disease. Together, this
      makes them promising targets for the treatment of chronic cough. This review will
      cover the current understanding of the role of the TRP family of ion channels in
      the activation of airway sensory nerves and cough, focusing on four members,
      transient receptor potential vanilloid (TRPV) 1, transient receptor potential
      ankyrin (TRPA) 1, TRPV4, and transient receptor potential melastatin (TRPM) 8 as
      these represent the channels where most information has been gathered with
      relevance to the airways. We will describe recent data and highlight the possible
      therapeutic utility of specific TRP channel antagonists as antitussives in the
      clinic. 

PMID- 25572386
TI  - Sex-related gene expression profiles in the adrenal cortex in the mature rat:
      microarray analysis with emphasis on genes involved in steroidogenesis.
AB  - Notable sex-related differences exist in mammalian adrenal cortex structure and
      function. In adult rats, the adrenal weight and the average volume of zona
      fasciculata cells of females are larger and secrete greater amounts of
      corticosterone than those of males. The molecular bases of these sex-related
      differences are poorly understood. In this study, to explore the molecular
      background of these differences, we defined zone- and sex-specific transcripts in
      adult male and female (estrous cycle phase) rats. Twelve-week-old rats of both
      genders were used and samples were taken from the zona glomerulosa (ZG) and zona
      fasciculata/reticularis (ZF/R) zones. Transcriptome identification was carried
      out using the Affymetrix((r)) Rat Gene 1.1 ST Array. The microarray data were
      compared by fold change with significance according to moderated t-statistics.
      Subsequently, we performed functional annotation clustering using the Gene
      Ontology (GO) and Database for Annotation, Visualization and Integrated Discovery
      (DAVID). In the first step, we explored differentially expressed transcripts in
      the adrenal ZG and ZF/R. The number of differentially expressed transcripts was
      notably higher in the female than in the male rats (702 vs. 571). The
      differentially expressed genes which were significantly enriched included genes
      involved in steroid hormone metabolism, and their expression levels in the ZF/R
      of adult female rats were significantly higher compared with those in the male
      rats. In the female ZF/R, when compared with that of the males, prevailing
      numbers of genes linked to cell fraction, oxidation/reduction processes, response
      to nutrients and to extracellular stimuli or steroid hormone stimuli were
      downregulated. The microarray data for key genes involved directly in
      steroidogenesis were confirmed by qPCR. Thus, when compared with that of the
      males, in the female ZF/R, higher expression levels of genes involved directly in
      steroid hormone synthesis were accompanied by lower expression levels of genes
      regulating basal cell functions.

PMID- 25572390
TI  - Correlating structural and energetic changes in glycine receptor activation.
AB  - Pentameric ligand-gated ion channels (pLGICs) mediate fast chemoelectrical
      transduction in the nervous system. The mechanism by which the energy of ligand
      binding leads to current-conducting receptors is poorly understood and may vary
      among family members. We addressed these questions by correlating the structural
      and energetic mechanisms by which a naturally occurring M1 domain mutation
      (alpha1(Q-26'E)) enhances receptor activation in homo- and heteromeric glycine
      receptors. We systematically altered the charge of spatially clustered residues
      at positions 19' and 24', in the M2 and M2-M3 linker domains, respectively, which
      are known to be critical to efficient receptor activation, on a background of
      alpha1(Q-26'E). Changes in the durations of single receptor activations
      (clusters) and conductance were used to determine interaction coupling energies,
      which we correlated with conformational displacements as measured in pLGIC
      crystal structures. Presence of the alpha1(Q-26'E) enhanced cluster durations and
      reduced channel conductance in homo- and heteromeric receptors. Strong coupling
      between alpha1(-26') and alpha1(19') across the subunit interface suggests an
      important role in receptor activation. A lack of coupling between alpha1(-26')
      and alpha1(24') implies that 24' mutations disrupt activation via other
      interactions. A similar lack of energetic coupling between alpha1(-26') and
      reciprocal mutations in the beta subunit suggests that this subunit remains
      relatively static during receptor activation. However, the channel effects of
      alpha1(Q-26'E) on alpha1beta receptors suggests at least one alpha1-alpha1
      interface per pentamer. The coupling-energy change between alpha1(-26') and
      alpha1(19') correlates with a local structural rearrangement essential for pLGIC
      activation, implying it comprises a key energetic pathway in activating glycine
      receptors and other pLGICs. 

PMID- 25572391
TI  - Defective repair of uracil causes telomere defects in mouse hematopoietic cells.
AB  - Uracil in the genome can result from misincorporation of dUTP instead of dTTP
      during DNA synthesis, and is primarily removed by uracil DNA glycosylase (UNG)
      during base excision repair. Telomeres contain long arrays of TTAGGG repeats and
      may be susceptible to uracil misincorporation. Using model telomeric DNA
      substrates, we showed that the position and number of uracil substitutions of
      thymine in telomeric DNA decreased recognition by the telomere single-strand
      binding protein, POT1. In primary mouse hematopoietic cells, uracil was
      detectable at telomeres, and UNG deficiency further increased uracil loads and
      led to abnormal telomere lengthening. In UNG-deficient cells, the frequencies of
      sister chromatid exchange and fragility in telomeres also significantly increased
      in the absence of telomerase. Thus, accumulation of uracil and/or UNG deficiency
      interferes with telomere maintenance, thereby underscoring the necessity of UNG
      initiated base excision repair for the preservation of telomere integrity. 

PMID- 25572392
TI  - Thyroid hormone receptor sumoylation is required for preadipocyte differentiation
      and proliferation.
AB  - Thyroid hormone and thyroid hormone receptor (TR) play an essential role in
      metabolic regulation. However, the role of TR in adipogenesis has not been
      established. We reported previously that TR sumoylation is essential for TR
      mediated gene regulation and that mutation of either of the two sites in TRalpha
      or any of the three sites in TRbeta reduces TR sumoylation. Here, we transfected
      TR sumoylation site mutants into human primary preadiocytes and the mouse 3T3L1
      preadipocyte cell line to determine the role of TR sumoylation in adipogenesis.
      Reduced sumoylation of TRalpha or TRbeta resulted in fewer and smaller lipid
      droplets and reduced proliferation of preadipocytes. TR sumoylation mutations,
      compared with wild-type TR, results in reduced C/EBP expression and reduced
      PPARgamma2 mRNA and protein levels. TR sumoylation mutants recruited NCoR and
      disrupted PPARgamma-mediated perilipin1 (Plin1) gene expression, associated with
      impaired lipid droplet formation. Expression of NCoRDeltaID, a mutant NCoR
      lacking the TR interaction domain, partially "rescued" the delayed adipogenesis
      and restored Plin1 gene expression and adipogenesis. TR sumoylation site mutants
      impaired Wnt/beta-catenin signaling pathways and the proliferation of primary
      human preadipocytes. Expression of the TRbeta K146Q sumoylation site mutant down
      regulated the essential genes required for canonical Wnt signal-mediated
      proliferation, including Wnt ligands, Fzds, beta-catenin, LEF1, and CCND1.
      Additionally, the TRbeta K146Q mutant enhanced the canonical Wnt signaling
      inhibitor Dickkopf-related protein 1 (DKK1). Our data demonstrate that TR
      sumoylation is required for activation of the Wnt canonical signaling pathway
      during preadipocyte proliferation and enhances the PPARgamma signaling that
      promotes differentiation. 

PMID- 25572393
TI  - The Aspergillus nidulans proline permease as a model for understanding the
      factors determining substrate binding and specificity of fungal amino acid
      transporters.
AB  - Amino acid uptake in fungi is mediated by general and specialized members of the
      yeast amino acid transporter (YAT) family, a branch of the amino acid polyamine
      organocation (APC) transporter superfamily. PrnB, a highly specific l-proline
      transporter, only weakly recognizes other Put4p substrates, its Saccharomyces
      cerevisiae orthologue. Taking advantage of the high sequence similarity between
      the two transporters, we combined molecular modeling, induced fit docking,
      genetic, and biochemical approaches to investigate the molecular basis of this
      difference and identify residues governing substrate binding and specificity. We
      demonstrate that l-proline is recognized by PrnB via interactions with residues
      within TMS1 (Gly(56), Thr(57)), TMS3 (Glu(138)), and TMS6 (Phe(248)), which are
      evolutionary conserved in YATs, whereas specificity is achieved by subtle amino
      acid substitutions in variable residues. Put4p-mimicking substitutions in TMS3
      (S130C), TMS6 (F252L, S253G), TMS8 (W351F), and TMS10 (T414S) broadened the
      specificity of PrnB, enabling it to recognize more efficiently l-alanine, l
      azetidine-2-carboxylic acid, and glycine without significantly affecting the
      apparent Km for l-proline. S253G and W351F could transport l-alanine, whereas
      T414S, despite displaying reduced proline uptake, could transport l-alanine and
      glycine, a phenotype suppressed by the S130C mutation. A combination of all five
      Put4p-ressembling substitutions resulted in a functional allele that could also
      transport l-alanine and glycine, displaying a specificity profile impressively
      similar to that of Put4p. Our results support a model where residues in these
      positions determine specificity by interacting with the substrates, acting as
      gating elements, altering the flexibility of the substrate binding core, or
      affecting conformational changes of the transport cycle. 

PMID- 25572394
TI  - Prion protein promotes kidney iron uptake via its ferrireductase activity.
AB  - Brain iron-dyshomeostasis is an important cause of neurotoxicity in prion
      disorders, a group of neurodegenerative conditions associated with the conversion
      of prion protein (PrP(C)) from its normal conformation to an aggregated, PrP
      scrapie (PrP(Sc)) isoform. Alteration of iron homeostasis is believed to result
      from impaired function of PrP(C) in neuronal iron uptake via its ferrireductase
      activity. However, unequivocal evidence supporting the ferrireductase activity of
      PrP(C) is lacking. Kidney provides a relevant model for this evaluation because
      PrP(C) is expressed in the kidney, and ~370 MUg of iron are reabsorbed daily from
      the glomerular filtrate by kidney proximal tubule cells (PT), requiring
      ferrireductase activity. Here, we report that PrP(C) promotes the uptake of
      transferrin (Tf) and non-Tf-bound iron (NTBI) by the kidney in vivo and mainly
      NTBI by PT cells in vitro. Thus, uptake of (59)Fe administered by gastric gavage,
      intravenously, or intraperitoneally was significantly lower in PrP-knock-out
      (PrP(-/-)) mouse kidney relative to PrP(+/+) controls. Selective in vivo
      radiolabeling of plasma NTBI with (59)Fe revealed similar results. Expression of
      exogenous PrP(C) in immortalized PT cells showed localization on the plasma
      membrane and intracellular vesicles and increased transepithelial transport of
      (59)Fe-NTBI and to a smaller extent (59)Fe-Tf from the apical to the basolateral
      domain. Notably, the ferrireductase-deficient mutant of PrP (PrP(Delta51-89))
      lacked this activity. Furthermore, excess NTBI and hemin caused aggregation of
      PrP(C) to a detergent-insoluble form, limiting iron uptake. Together, these
      observations suggest that PrP(C) promotes retrieval of iron from the glomerular
      filtrate via its ferrireductase activity and modulates kidney iron metabolism. 

PMID- 25572396
TI  - The oligomeric outer dynein arm assembly factor CCDC103 is tightly integrated
      within the ciliary axoneme and exhibits periodic binding to microtubules.
AB  - CCDC103 is an ~29-kDa protein consisting of a central RPAP3_C domain flanked by N
      and C-terminal coiled coils. Defects in CCDC103 lead to primary ciliary
      dyskinesia caused by the loss of outer dynein arms. This protein is present along
      the entire length of the ciliary axoneme and does not require other dynein or
      docking complex components for its integration. Unlike other known dynein
      assembly factors within the axoneme, CCDC103 is not solubilized by 0.6 M NaCl and
      requires more chaotropic conditions, such as 0.5 M KI. Alternatively, it can be
      extracted using 0.3% sarkosyl. CCDC103 forms stable dimers and other oligomers in
      solution through interactions involving the central domain. The smallest particle
      observed by dynamic light scattering has a hydrodynamic diameter of ~25 nm.
      Furthermore, CCDC103 binds microtubules directly, forming ~9-nm diameter
      particles that exhibit a 12-nm spacing on the microtubule lattice, suggesting
      that there may be two CCDC103 units per outer arm dynein repeat. Although the
      outer dynein arm docking complex is necessary to form arrays of dyneins along
      microtubules, it is not sufficient to set up a single array in a precise location
      on each axonemal doublet. We propose that CCDC103 helps generate a high-affinity
      site on the doublets for outer arm assembly, either through direct interactions
      or indirectly, perhaps by modifying the underlying microtubule lattice.

PMID- 25572395
TI  - ClipR-59 interacts with Elmo2 and modulates myoblast fusion.
AB  - Recent studies using ClipR-59 knock-out mice implicated this protein in the
      regulation of muscle function. In this report, we have examined the role of ClipR
      59 in muscle differentiation and found that ClipR-59 knockdown in C2C12 cells
      suppressed myoblast fusion. To elucidate the molecular mechanism whereby ClipR-59
      regulates myoblast fusion, we carried out a yeast two-hybrid screen using ClipR
      59 as the bait and identified Elmo2, a member of the Engulfment and cell motility
      protein family, as a novel ClipR-59-associated protein. We showed that the
      interaction between ClipR-59 and Elmo2 was mediated by the atypical PH domain of
      Elmo2 and the Glu-Pro-rich domain of ClipR-59 and regulated by Rho-GTPase. We
      have examined the impact of ClipR-59 on Elmo2 downstream signaling and found that
      interaction of ClipR-59 with Elmo2 enhanced Rac1 activation. Collectively, our
      studies demonstrate that formation of an Elmo2.ClipR-59 complex plays an
      important role in myoblast fusion. 

PMID- 25572397
TI  - Mechanisms mediating enhanced neutralization efficacy of staphylococcal
      enterotoxin B by combinations of monoclonal antibodies.
AB  - Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major
      histocompatibility complex class II and specific V-beta chains of the T-cell
      receptor, thus forming a ternary complex. Developing neutralizing mAb to disrupt
      the ternary complex and abrogate the resulting toxicity is a major therapeutic
      challenge because SEB is effective at very low concentrations. We show that
      combining two SEB-specific mAbs enhances their efficacy, even though one of the
      two mAbs by itself has no effect on neutralization. Crystallography was employed
      for fine-mapping conformational epitopes in binary and ternary complexes between
      SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle
      allosteric changes induced by mAbs binding to SEB. The mapping of epitopes
      established that a combination of different mAbs can enhance efficacy of mAb
      mediated protection from SEB induced lethal shock by two different mechanisms:
      one mAb mixture promoted clearance of the toxin both in vitro and in vivo by FcR
      mediated cross-linking and clearance, whereas the other mAb mixture induced
      subtle allosteric conformational changes in SEB that perturbed formation of the
      SEB.T-cell receptor.major histocompatibility complex class II trimer. Finally
      structural information accurately predicted mAb binding to other superantigens
      that share conformational epitopes with SEB. Fine mapping of conformational
      epitopes is a powerful tool to establish the mechanism and optimize the action of
      synergistic mAb combinations. 

PMID- 25572398
TI  - Suppression of shrimp melanization during white spot syndrome virus infection.
AB  - The melanization cascade, activated by the prophenoloxidase (proPO) system, plays
      a key role in the production of cytotoxic intermediates, as well as melanin
      products for microbial sequestration in invertebrates. Here, we show that the
      proPO system is an important component of the Penaeus monodon shrimp immune
      defense toward a major viral pathogen, white spot syndrome virus (WSSV). Gene
      silencing of PmproPO(s) resulted in increased cumulative shrimp mortality after
      WSSV infection, whereas incubation of WSSV with an in vitro melanization reaction
      prior to injection into shrimp significantly increased the shrimp survival rate.
      The hemolymph phenoloxidase (PO) activity of WSSV-infected shrimp was extremely
      reduced at days 2 and 3 post-injection compared with uninfected shrimp but was
      fully restored after the addition of exogenous trypsin, suggesting that WSSV
      probably inhibits the activity of some proteinases in the proPO cascade. Using
      yeast two-hybrid screening and co-immunoprecipitation assays, the viral protein
      WSSV453 was found to interact with the proPO-activating enzyme 2 (PmPPAE2) of P.
      monodon. Gene silencing of WSSV453 showed a significant increase of PO activity
      in WSSV-infected shrimp, whereas co-silencing of WSSV453 and PmPPAE2 did not,
      suggesting that silencing of WSSV453 partially restored the PO activity via
      PmPPAE2 in WSSV-infected shrimp. Moreover, the activation of PO activity in
      shrimp plasma by PmPPAE2 was significantly decreased by preincubation with
      recombinant WSSV453. These results suggest that the inhibition of the shrimp
      proPO system by WSSV partly occurs via the PmPPAE2-inhibiting activity of
      WSSV453. 

PMID- 25572399
TI  - Catecholamine stress hormones regulate cellular iron homeostasis by a
      posttranscriptional mechanism mediated by iron regulatory protein: implication in
      energy homeostasis.
AB  - Adequate availability of iron is important for cellular energy metabolism.
      Catecholamines such as epinephrine and norepinephrine promote energy expenditure
      to adapt to conditions that arose due to stress. To restore the energy balance,
      epinephrine/norepinephrine-exposed cells may face higher iron demand. So far, no
      direct role of epinephrine/norepinephrine in cellular iron homeostasis has been
      reported. Here we show that epinephrine/norepinephrine regulates iron homeostasis
      components such as transferrin receptor-1 and ferritin-H in hepatic and skeletal
      muscle cells by promoting the binding of iron regulatory proteins to iron
      responsive elements present in the UTRs of transferrin receptor-1 and ferritin-H
      transcripts. Increased transferrin receptor-1, decreased ferritin-H, and
      increased iron-responsive element-iron regulatory protein interaction are also
      observed in liver and muscle tissues of epinephrine/norepinephrine-injected mice.
      We demonstrate the role of epinephrine/norepinephrine-induced generation of
      reactive oxygen species in converting cytosolic aconitase (ACO1) into iron
      regulatory protein-1 to bind iron-responsive elements present in UTRs of
      transferrin receptor-1 and ferritin-H. Our study further reveals that
      mitochondrial iron content and mitochondrial aconitase (ACO2) activity are
      elevated by epinephrine/norepinephrine that are blocked by the antioxidant N
      acetyl cysteine and iron regulatory protein-1 siRNA, suggesting involvement of
      reactive oxygen species and iron regulatory protein-1 in this mechanism. This
      study reveals epinephrine and norepinephrine as novel regulators of cellular iron
      homeostasis. 

PMID- 25572400
TI  - Cyclin-dependent kinase 5 phosphorylation of familial prion protein mutants
      exacerbates conversion into amyloid structure.
AB  - Familial prion protein (PrP) mutants undergo conversion from soluble and protease
      sensitive to insoluble and partially protease-resistant proteins. Cyclin
      dependent kinase 5 (Cdk5) phosphorylation of wild type PrP (pPrP) at serine 43
      induces a conversion of PrP into aggregates and fibrils. Here, we investigated
      whether familial PrP mutants are predisposed to Cdk5 phosphorylation and whether
      phosphorylation of familial PrP mutants increases conversion. PrP mutants
      representing three major familial PrP diseases and different PrP structural
      domains were studied. We developed a novel in vitro kinase reaction coupled with
      Thioflavin T binding to amyloid structure assay to monitor phosphorylation
      dependent amyloid conversion. Although non-phosphorylated full-length wild type
      or PrP mutants did not convert into amyloid, Cdk5 phosphorylation rapidly
      converted these into Thioflavin T-positive structures following first order
      kinetics. Dephosphorylation partially reversed conversion. Phosphorylation
      dependent conversion of PrP from alpha-helical structures into beta-sheet
      structures was confirmed by circular dichroism. Relative to wild type pPrP, most
      PrP mutants showed increased rate constants of conversion. In contrast, non
      phosphorylated truncated PrP Y145X (where X represents a stop codon) and Q160X
      mutants converted spontaneously into Thioflavin T-positive fibrils after a lag
      phase of over 20 h, indicating nucleation-dependent polymerization.
      Phosphorylation reduced the lag phase by over 50% and thus accelerated the
      formation of the nucleating event. Consistently, phosphorylated Y145X and
      phosphorylated Q160X exacerbated conversion in a homologous seeding reaction,
      whereas WT pPrP could not seed WT PrP. These results demonstrate an influence of
      both the N terminus and the C terminus of PrP on conversion. We conclude that
      post-translational modifications of the flexible N terminus of PrP can cause or
      exacerbate PrP mutant conversion. 

PMID- 25572403
TI  - A solution-phase approach to Cd3P2 nanowires: synthesis and characterization.
AB  - Single-crystalline Cd3P2 nanowires (NWs) have been synthesized via a solution
      liquid-solid (SLS) mechanism. The lengths of the resulting nanowires can be
      effectively tuned in the range of 180 nm and 5 MUm, and the photodetectors made
      of the Cd3P2 nanowires exhibited a pronounced photoresponse with high stability
      and reproducibility. 

PMID- 25572402
TI  - Phosphatidylinositol 4,5-bisphosphate clusters the cell adhesion molecule CD44
      and assembles a specific CD44-Ezrin heterocomplex, as revealed by small angle
      neutron scattering.
AB  - The cell adhesion molecule CD44 regulates diverse cellular functions, including
      cell-cell and cell-matrix interaction, cell motility, migration, differentiation,
      and growth. In cells, CD44 co-localizes with the membrane-cytoskeleton adapter
      protein Ezrin that links the CD44 assembled receptor signaling complexes to the
      cytoskeletal actin network, which organizes the spatial and temporal localization
      of signaling events. Here we report that the cytoplasmic tail of CD44 (CD44ct) is
      largely disordered. Upon binding to the signaling lipid phosphatidylinositol 4,5
      bisphosphate (PIP2), CD44ct clusters into aggregates. Further, contrary to the
      generally accepted model, CD44ct does not bind directly to the FERM domain of
      Ezrin or to the full-length Ezrin but only forms a complex with FERM or with the
      full-length Ezrin in the presence of PIP2. Using contrast variation small angle
      neutron scattering, we show that PIP2 mediates the assembly of a specific
      heterotetramer complex of CD44ct with Ezrin. This study reveals the role of PIP2
      in clustering CD44 and in assembling multimeric CD44-Ezrin complexes. We
      hypothesize that polyvalent electrostatic interactions are responsible for the
      assembly of CD44 clusters and the multimeric PIP2-CD44-Ezrin complexes. 

PMID- 25572401
TI  - A unique phenylalanine in the transmembrane domain strengthens homodimerization
      of the syndecan-2 transmembrane domain and functionally regulates syndecan-2.
AB  - The syndecans are a type of cell surface adhesion receptor that initiates
      intracellular signaling events through receptor clustering mediated by their
      highly conserved transmembrane domains (TMDs). However, the exact function of the
      syndecan TMD is not yet fully understood. Here, we investigated the specific
      regulatory role of the syndecan-2 TMD. We found that syndecan-2 mutants in which
      the TMD had been replaced with that of syndecan-4 were defective in syndecan-2
      mediated functions, suggesting that the TMD of syndecan-2 plays one or more
      specific roles. Interestingly, syndecan-2 has a stronger tendency to form sodium
      dodecyl sulfate (SDS)-resistant homodimers than syndecan-4. Our structural
      studies showed that a unique phenylalanine residue (Phe(167)) enables an
      additional molecular interaction between the TMDs of the syndecan-2 homodimer.
      The presence of Phe(167) was correlated with a higher tendency toward
      oligomerization, and its replacement with isoleucine significantly reduced the
      SDS-resistant dimer formation and cellular functions of syndecan-2 (e.g. cell
      migration). Conversely, replacement of isoleucine with phenylalanine at this
      position in the syndecan-4 TMD rescued the defects observed in a mutant syndecan
      2 harboring the syndecan-4 TMD. Taken together, these data suggest that Phe(167)
      in the TMD of syndecan-2 endows the protein with specific functions. Our work
      offers new insights into the signaling mediated by the TMD of syndecan family
      members. 

PMID- 25572404
TI  - Genetic targeting of a small fluorescent zinc indicator to cell surface for
      monitoring zinc secretion.
AB  - Numerous mammalian cells contain Zn2+ in their secretory granules. During
      secretion, Zn2+ is coreleased with granular cargos into extracellular medium so
      Zn2+ serves as a convenient surrogate marker for tracking the dynamics of
      secretion. Fluorescent Zn2+ sensors that can be selectively targeted to cells of
      interest would be invaluable tools for imaging Zn2+ release in multicellular
      systems including tissues and live animals. Exploiting the HaloTag labeling
      technology and using an optimized linker, we have engineered a fluorescent Zn2+
      indicator that displayed a 15-fold fluorescence enhancement upon Zn2+ binding
      while reacting efficiently with a HaloTag enzyme in a cellular environment. Two
      color imaging of ZIMIR-HaloTag and a red-emitting calcium indicator in pancreatic
      islet beta cells demonstrated that photoactivation of a channelrhodopsin was able
      to induce exocytosis of Zn2+/insulin granules and revealed heterogeneity in
      secretory activity along the cell membrane that was uncoupled from cellular Ca2+
      activity. This integrated photonic approach for imaging and controlling the
      release of large dense core granules provides exquisite cellular selectivity and
      should facilitate future studies of stimulus-secretion coupling and paracrine
      signaling in secretory cells.

PMID- 25572406
TI  - The impact of CRISPR-Cas9 on target identification and validation.
AB  - The addition of an RNA-guided nuclease, Cas9, to the gene editing toolbox has
      increased the accessibility of gene editing technologies by greatly simplifying
      the design of editing reagents. Only a single 75-100 nucleotide RNA is required
      to guide Cas9 to the target gene of interest, which has meant that the
      established infrastructure of short-hairpin RNA interference screen could be
      readily adapted to genome-wide knock out screens. Cas9-based editing technology
      should streamline the generation of animal and cell-line models, make the
      generation of activity-dead mutations in target validation routine, and enable
      the discovery of a new generation of targets across therapeutic areas. 

PMID- 25572407
TI  - Considerations in the early development of biosimilar products.
AB  - The widespread use and patent expiration of many biologics have led to global
      interest in development of biosimilar products. Because the manufacture of
      biologics, including biosimilars, is a complex process involving living systems,
      the development of a biosimilar is more rigorous than the development of a
      generic small molecule drug. Several regulatory agencies have established or are
      proposing guidelines that recommend a stepwise process to ensure the efficacy and
      safety of a biosimilar are highly similar to the reference product. This article
      also explores the early clinical phase of biosimilar development, which is
      particularly important to resolving any uncertainties that might remain following
      in vitro and in vivo evaluations and to enable a selective and targeted approach
      to Phase III clinical efficacy and safety investigation. 

PMID- 25572408
TI  - Impact of plant development on the rhizobacterial population of Arachis hypogaea:
      a multifactorial analysis.
AB  - Present study investigates the impact of plant development on the structure and
      composition of root-associated bacterial community of groundnut (Arachis
      hypogaea) plant, an economically important oilseed legume. Relative abundance of
      total and active bacteria were studied in bulk soil and rhizosphere samples
      collected from different growth stages of groundnut plant by sequencing PCR
      amplified 16S rRNA gene fragments from soil genomic DNA and reverse-transcribed
      soil community RNA. Plant growth promoting potential of cultivable rhizobacteria
      was evaluated using assays for inorganic phosphate solubilization and production
      of indole acetic acid, siderophores, biofilm, 1-amino-cyclopropane-1-carboxylate
      deaminase, laccase, and anti-fungal chemicals. Our study demonstrates that
      groundnut plant rhizosphere harbors a core microbiome populated by
      Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, and Acidobacteria. A
      distinct bacterial assemblage at nodulation stage due to predominance of
      Flavobacteria and Actinobacteria in DNA and RNA derived libraries respectively
      was also observed. Majority of cultivable isolates exhibiting plant growth
      promoting activities belonged to Proteobacteria and Firmicutes. Of them,
      Pseudomonas indica and Bacillus megaterium were detected in the rhizosphere
      samples from all the developmental stages of groundnut plant. This polyphasic
      study establishes the impact of plant development on rhizobacterial population of
      groundnut and underscores the applicability of soil isolates as a reliable
      component in sustainable agriculture. 

PMID- 25572409
TI  - Letter by turc et Al regarding article, "defining clinically relevant cerebral
      hemorrhage after thrombolytic therapy for stroke: analysis of the national
      institute of neurological disorders and stroke tissue-type plasminogen activator
      trials".

PMID- 25572410
TI  - Response to letter regarding article, "defining clinically relevant cerebral
      hemorrhage after thrombolytic therapy for stroke: analysis of the national
      institute of neurological disorders and stroke tissue-type plasminogen activator
      trials".

PMID- 25572405
TI  - Epigenetic mechanisms in heart development and disease.
AB  - Suboptimal intrauterine development has been linked to predisposition to
      cardiovascular disease in adulthood, a concept termed 'developmental origins of
      health and disease'. Although the exact mechanisms underlying this developmental
      programming are unknown, a growing body of evidence supports the involvement of
      epigenetic regulation. Epigenetic mechanisms such as DNA methylation, histone
      modifications and micro-RNA confer added levels of gene regulation without
      altering DNA sequences. These modifications are relatively stable signals,
      offering possible insight into the mechanisms underlying developmental origins of
      health and disease. This review will discuss the role of epigenetic mechanisms in
      heart development as well as aberrant epigenetic regulation contributing to
      cardiovascular disease. Additionally, we will address recent advances targeting
      epigenetic mechanisms as potential therapeutic approaches to cardiovascular
      disease. 

PMID- 25572411
TI  - Relationship between white matter hyperintensities, cortical thickness, and
      cognition.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are associated with
      clinically heterogeneous symptoms that cannot be explained by these lesions
      alone. It is hypothesized that these lesions are associated with distant cortical
      atrophy and cortical thickness network measures, which can result in an
      additional cognitive impairment. Here, we investigated the relationships between
      WMH, cortical thickness, and cognition in subjects with cerebral small vessel
      disease. METHODS: A total of 426 subjects with cerebral small vessel disease were
      included, aged between 50 and 85 years, without dementia, and underwent MRI
      scanning. Cortical thickness analysis was performed, and WMH were manually
      segmented. Graph theory was applied to examine the relationship between network
      measures and WMH, and structural covariance matrices were constructed using inter
      regional cortical thickness correlations. RESULTS: Higher WMH load was related to
      lower cortical thickness in frontotemporal regions, whereas in paracentral
      regions, this was related to higher cortical thickness. Network analyses revealed
      that measures of network disruption were associated with WMH and cognitive
      performance. Furthermore, WMH in specific white matter tracts were related to
      regional-specific cortical thickness and network measures. Cognitive performances
      were related to cortical thickness in frontotemporal regions and network
      measures, and not to WMH, while controlling for cortical thickness. CONCLUSIONS:
      These cross-sectional results suggest that cortical changes (regional-specific
      damage and network breakdown), mediated (in)directly by WMH (tract-specific
      damage) and other factors (eg, vascular risk factors), might lead to cognitive
      decline. These findings have implications in understanding the relationship
      between WMH, cortical morphology, and the possible attendant cognitive decline
      and eventually dementia.

PMID- 25572412
TI  - You may have worked on more adaptive designs than you think.

PMID- 25572413
TI  - Is prophylactic anticoagulation for deep venous thrombosis common practice after
      intracerebral hemorrhage?
AB  - BACKGROUND AND PURPOSE: Prophylactic anticoagulation for deep venous thrombosis
      prevention after intracerebral hemorrhage (ICH) is safe. Current guidelines
      recommend prophylactic anticoagulation after cessation of hematoma growth. We
      aimed to evaluate nationwide trends in deep venous thrombosis prophylaxis after
      ICH. METHODS: In an analysis of the Premier database, we identified adult
      patients with ICH (International Classification of Diseases Ninth edition code
      431) from 2006 to 2010 who survived to day 2 of hospitalization. We excluded
      those with trauma or who underwent craniotomy or angiography. We abstracted type
      of anticoagulant used and date of first administration. We used univariate
      statistics and multivariable logistic regression to assess factors associated
      with prophylactic anticoagulation after ICH. RESULTS: Among 32 690 (mean age,
      69.7 years; 50.1% men) patients with spontaneous ICH, 5395 (16.5%) patients
      received any prophylactic anticoagulation during the hospital stay. Among these
      patients, 2416 (44.8%) received prophylactic anticoagulation by day 2. The most
      commonly used agents were heparin (71.1%), enoxaparin (27.5%), and dalteparin
      (1.4%). The proportion of patients receiving prophylactic anticoagulation
      increased slightly during the study period from 14.3% to 18.0% (P<0.01 for
      trend). Use of prophylactic anticoagulation varied by geographic region (P<0.001)
      in the United States: Northeast (23.2%), South (19.0%), Midwest (10.8%), and West
      (9.8%). In multivariable analysis, geographic region remained an independent
      predictor of prophylactic anticoagulation. CONCLUSIONS: Less than 20% of patients
      with ICH receive anticoagulation for deep venous thrombosis in the United States.
      When used, the time to initiation is <2 days in less than half of the patients.
      Further study should focus on understanding variations in practice and emphasize
      guideline-driven care.

PMID- 25572414
TI  - Arsenic trioxide-induced cytotoxicity in small cell lung cancer via altered redox
      homeostasis and mitochondrial integrity.
AB  - Arsenic trioxide (ATO) has demonstrated anticancer activity in different
      malignancies, especially acute promyelocytic leukemia, with a wide array of
      putative mechanisms. In this study, we aimed to elucidate the activity and
      mechanisms of ATO in small cell lung cancer (SCLC). A panel of SCLC cell lines
      (H841, DMS79, H526, H69 and H187) was employed to demonstrate the activity of
      ATO. Cell viability, apoptosis and mitochondrial membrane depolarization were
      assessed. Western blotting was performed to determine the alteration of pro
      apoptotic and anti-apoptotic mediators. Reactive oxygen species (ROS) (hydrogen
      peroxide and superoxide) and intracellular glutathione (GSH) were measured.
      Antioxidants, N-acetyl-L-cysteine (NAC) and butylated hydroxyanisole (BHA), were
      applied to restore GSH content and reduce production of ROS. All SCLC cell lines
      were relatively sensitive to ATO with IC50 values below 10 uM. ATO induced cell
      death mainly through apoptosis in H841 cells in a dose-dependent manner. Hydrogen
      peroxide was the major ROS in SCLC cells induced by ATO. Along with GSH depletion
      and Bcl-2 downregulation, mitochondrial membrane permeabilization was enhanced,
      followed by release of AIF and SMAC from mitochondria to initiate different cell
      death pathways. NAC reversed cell death and molecular changes induced by ATO via
      restoring GSH and reducing ROS content. BHA inhibited hydrogen peroxide
      production completely and partially restored GSH content accounting for partial
      reversal of cell inhibition and mitochondrial dysfunction. Nonetheless, ATO
      reduced both reduced and oxidized form of thioredoxin 1 (Trx1) with no effect on
      Trx1 redox potential. ATO led to cell death in SCLC mainly through mitochondrial
      dysfunction, resulting from altered cellular redox homeostasis, namely, hydrogen
      peroxide generation, GSH depletion and Trx1 downregulation.

PMID- 25572415
TI  - Magnitudes of biomarker reductions in response to controlled reductions in
      cigarettes smoked per day: a one-week clinical confinement study.
AB  - Tobacco toxicant-related exposure reduction is an important tool in harm
      reduction. Cigarette per day reduction (CPDR) occurs as smokers migrate from
      smoking cigarettes to using alternative tobacco/nicotine products, or quit
      smoking. Few reports characterize the dose-response relationships between CPDR
      and effects on exposure biomarkers, especially at the low end of CPD exposure
      (e.g., 5 CPD). We present data on CPDR by characterizing magnitudes of biomarker
      reductions. We present data from a well-controlled, one-week clinical confinement
      study in healthy smokers who were switched from smoking 19-25 CPD to smoking 20,
      10, 5 or 0 CPD. Biomarkers were measured in blood, plasma, urine, and breath, and
      included smoke-related toxicants, urine mutagenicity, smoked cigarette filter
      analyses (mouth level exposure), and vital signs. Many of the biomarkers (e.g.,
      plasma nicotine) showed strong CPDR dose-response reductions, while others (e.g.,
      plasma thiocyanate) showed weaker dose-response reductions. Factors that lead to
      lower biomarker reductions include non-CPD related contributors to the measured
      response (e.g., other exposure sources from environment, life style, occupation;
      inter-individual variability). This study confirms CPDR dose-responsive
      biomarkers and suggests that a one-week design is appropriate for characterizing
      exposure reductions when smokers switch from cigarettes to new tobacco products. 

PMID- 25572416
TI  - What is the difference between the breakpoint graph and the de Bruijn graph?
AB  - The breakpoint graph and the de Bruijn graph are two key data structures in the
      studies of genome rearrangements and genome assembly. However, the classical
      breakpoint graphs are defined on two genomes (represented as sequences of synteny
      blocks), while the classical de Bruijn graphs are defined on a single genome
      (represented as DNA strings). Thus, the connection between these two graph models
      is not explicit. We generalize the notions of both the breakpoint graph and the
      de Bruijn graph, and make it transparent that the breakpoint graph and the de
      Bruijn graph are mathematically equivalent. The explicit description of the
      connection between these important data structures provides a bridge between two
      previously separated bioinformatics communities studying genome rearrangements
      and genome assembly. 

PMID- 25572418
TI  - Oral symptoms and oral function in people with Sjogren's syndrome.

PMID- 25572417
TI  - Preparation of betulinic acid nanoemulsions stabilized by omega-3 enriched
      phosphatidylcholine.
AB  - Bioactive compounds such as omega-3 fatty acids and terpenes, have been
      associated with beneficial health effects; however, their solubility in the
      gastrointestinal tract and its bioavailability in the body are low. Nanoemulsions
      offer a viable alternative to disperse lipophilic compounds and improve their
      dissolution, permeation, absorption and bioavailability. Enzyme modified
      phosphatidylcholine (PC) with omega-3 fatty acids was used as emulsifier to
      stabilize oil-in-water nanoemulsions generated using ultrasound device. These
      systems were used as carriers of betulinic acid, which has reported anti
      carcinogenic activity. Phospholipase-catalyzed modification of PC allowed the
      incorporation of 50 mol% of omega-3 fatty acids. Formation variables such as oil
      type and ultrasound amplitude had effects on nanoemulsion characteristics.
      Incorporation of betulinic acid affected globule size; however, betulinic acid
      nanoemulsions below 200 nm could be prepared. The conditions under which
      betulinic acid nanoemulsions were obtained using the modified phosphatidylcholine
      with the smaller globule size (91 nm) were 10% PC, 25% glycerol, medium chain oil
      and 30% amplitude for 12 min in the sonicator. Storage temperature had an effect
      on the stability of the nanoemulsions, at 5 degrees C we observed the smallest
      growth in globule size. The use of olive oil decreased the globule size growth
      during storage of the nanoemulsion stabilized with modified phosphatidylcholine,
      although globule size obtained was greater than 200 nm. Medium pH had a
      significant effect on the nanoemulsions; alkaline pH values improved storage
      stability. These results provide useful information for using this type of
      carrier system on the formulation of products in the pharmaceutical or food
      industry.

PMID- 25572419
TI  - Chemotactic response with a constant delay-time mechanism in Ciona spermatozoa
      revealed by a high time resolution analysis of flagellar motility.
AB  - During their chemotactic swimming toward eggs, sperm cells detect their species
      specific chemoattractant and sense concentration gradients by unknown mechanisms.
      After sensing the attractant, sperm cells commonly demonstrate a series of
      responses involving different swimming patterns by changing flagellar beats,
      gradually approaching a swimming path toward the eggs, which is the source of
      chemoattractants. Shiba et al. observed a rapid increase in intracellular Ca(2+)
      concentrations in Ciona spermatozoa after sensing chemoattractants; however, the
      biochemical processes occurring inside the sperm cells are unclear. In the
      present study, we focused on the timing and sensing mechanism of chemical signal
      detection in Ciona. One of the most crucial problems to be solved is defining the
      initial epoch of chemotactic responses. We adopted a high rate of video recording
      (600 Hz) for detailed analysis of sperm motion and a novel method for detecting
      subtle signs of beat forms and moving paths of sperm heads. From these analyses,
      we estimated a virtual sensing point of the attractant before initiation of
      motility responses and found that the time delay from sensing to motility
      responses was almost constant. To evaluate the efficiency of this constant delay
      model, we performed computer simulation of chemotactic behaviors of Ciona
      spermatozoa. 

PMID- 25572420
TI  - ICAM-5 affects spine maturation by regulation of NMDA receptor binding to alpha
      actinin.
AB  - ICAM-5 is a negative regulator of dendritic spine maturation and facilitates the
      formation of filopodia. Its absence results in improved memory functions, but the
      mechanisms have remained poorly understood. Activation of NMDA receptors induces
      ICAM-5 ectodomain cleavage through a matrix metalloproteinase (MMP)-dependent
      pathway, which promotes spine maturation and synapse formation. Here, we report a
      novel, ICAM-5-dependent mechanism underlying spine maturation by regulating the
      dynamics and synaptic distribution of alpha-actinin. We found that GluN1 and ICAM
      5 partially compete for the binding to alpha-actinin; deletion of the cytoplasmic
      tail of ICAM-5 or ablation of the gene resulted in increased association of GluN1
      with alpha-actinin, whereas internalization of ICAM-5 peptide perturbed the
      GluN1/alpha-actinin interaction. NMDA treatment decreased alpha-actinin binding
      to ICAM-5, and increased the binding to GluN1. Proper synaptic distribution of
      alpha-actinin requires the ICAM-5 cytoplasmic domain, without which alpha-actinin
      tended to accumulate in filopodia, leading to F-actin reorganization. The results
      indicate that ICAM-5 retards spine maturation by preventing reorganization of the
      actin cytoskeleton, but NMDA receptor activation is sufficient to relieve the
      brake and promote the maturation of spines. 

PMID- 25572421
TI  - H3K36 Trimethylation-Mediated Epigenetic Regulation is Activated by Bam and
      Promotes Germ Cell Differentiation During Early Oogenesis in Drosophila.
AB  - Epigenetic silencing is critical for maintaining germline stem cells in
      Drosophila ovaries. However, it remains unclear how the differentiation factor,
      Bag-of-marbles (Bam), counteracts transcriptional silencing. We found that the
      trimethylation of lysine 36 on histone H3 (H3K36me3), a modification that is
      associated with gene activation, is enhanced in Bam-expressing cells. H3K36me3
      levels were reduced in flies deficient in Bam. Inactivation of the Set2
      methyltransferase, which confers the H3K36me3 modification, in germline cells
      markedly reduced H3K36me3 and impaired differentiation. Genetic analyses revealed
      that Set2 acts downstream of Bam. Furthermore, orb expression, which is required
      for germ cell differentiation, was activated by Set2, probably through direct
      H3K36me3 modification of the orb locus. Our data indicate that H3K36me3-mediated
      epigenetic regulation is activated by bam, and that this modification facilitates
      germ cell differentiation, probably through transcriptional activation. This work
      provides a novel link between Bam and epigenetic transcriptional control. 

PMID- 25572422
TI  - Modelling of soldier fly halteres for gyroscopic oscillations.
AB  - Nature has evolved a beautiful design for small-scale vibratory rate-gyro in the
      form of dipteran halteres that detect body rotations via Coriolis acceleration.
      In most Diptera, including soldier fly, Hermetia illucens, halteres are a pair of
      special organs, located in the space between the thorax and the abdomen. The
      halteres along with their connecting joint with the fly's body constitute a
      mechanism that is used for muscle-actuated oscillations of the halteres along the
      actuation direction. These oscillations lead to bending vibrations in the sensing
      direction (out of the haltere's actuation plane) upon any impressed rotation due
      to the resulting Coriolis force. This induced vibration is sensed by the sensory
      organs at the base of the haltere in order to determine the rate of rotation. In
      this study, we evaluate the boundary conditions and the stiffness of the
      anesthetized halteres along the actuation and the sensing direction. We take
      several cross-sectional SEM (scanning electron microscope) images of the soldier
      fly haltere and construct its three dimensional model to get the mass properties.
      Based on these measurements, we estimate the natural frequency along both
      actuation and sensing directions, propose a finite element model of the haltere's
      joint mechanism, and discuss the significance of the haltere's asymmetric cross
      section. The estimated natural frequency along the actuation direction is within
      the range of the haltere's flapping frequency. However, the natural frequency
      along the sensing direction is roughly double the haltere's flapping frequency
      that provides a large bandwidth for sensing the rate of rotation to the soldier
      flies. 

PMID- 25572423
TI  - Proper migration and axon outgrowth of zebrafish cranial motoneuron
      subpopulations require the cell adhesion molecule MDGA2A.
AB  - The formation of functional neuronal circuits relies on accurate migration and
      proper axonal outgrowth of neuronal precursors. On the route to their targets
      migrating cells and growing axons depend on both, directional information from
      neurotropic cues and adhesive interactions mediated via extracellular matrix
      molecules or neighbouring cells. The inactivation of guidance cues or the
      interference with cell adhesion can cause severe defects in neuronal migration
      and axon guidance. In this study we have analyzed the function of the MAM domain
      containing glycosylphosphatidylinositol anchor 2A (MDGA2A) protein in zebrafish
      cranial motoneuron development. MDGA2A is prominently expressed in distinct
      clusters of cranial motoneurons, especially in the ones of the trigeminal and
      facial nerves. Analyses of MDGA2A knockdown embryos by light sheet and confocal
      microscopy revealed impaired migration and aberrant axonal outgrowth of these
      neurons; suggesting that adhesive interactions mediated by MDGA2A are required
      for the proper arrangement and outgrowth of cranial motoneuron subtypes. 

PMID- 25572424
TI  - A unique mechanism of successful fertilization in a domestic bird.
AB  - Fertilization is an indispensable step for formation of a zygote in sexual
      reproduction, leading to species survival. When mating occurs, sperm is
      transported to the female reproductive tracts via the seminal plasma (SP). SP is
      derived from male accessory sex glands and it plays pivotal roles for
      fertilization in animals. However, molecular mechanisms of SP or a fluid derived
      from male accessory sex glands for successful fertilization remain unclear. Here,
      we report that in male quail the cloacal gland (CG) produces prostaglandin
      F2alpha (PGF2alpha) that contributes to successful fertilization. PGF2alpha, as
      well as the secretion of CG (CGS), induced vaginal contractions and caused the
      opening of the entrance of the sperm storage tubules, the structures responsible
      for the long-term sperm storage and fertilization. The removal of CGS from the
      male before mating reduced the fertility, but the supplementation of CGS or
      PGF2alpha rescued the subfertility. We further showed that male CG contains
      glucose that is utilized as energy source for the intrinsic sperm mobility after
      transportation to female vagina. This mechanism, in concert with the excitatory
      effects of PGF2alpha enables successful fertilization in the domestic bird. 

PMID- 25572425
TI  - TLR8 gene polymorphism and association in bacterial load in southern Punjab of
      Pakistan: an association study with pulmonary tuberculosis.
AB  - Only 5-10% of people infected with Mycobacterium tuberculosis develop active
      tuberculosis which suggests a role of genetic variation in host immunity. Genetic
      variants in TLRs are potential indicator for host susceptibility and outcome of
      several diseases. We explored the association of nonsynonymous genetic variants
      (Met1Val) with Toll-like receptor 8 in Pakistani population. Genotypic and
      allelic distribution of TLR8 polymorphism (rs3764880) in patients with TB and
      healthy donors from different areas of southern Punjab, Pakistan, was determined.
      Results provide that our population is highly influenced by TLR8 Met1Val SNP for
      TB, and G allele appeared to increase TB susceptibility. Mutant genotype GG or G/
      and G allele was significantly higher among all the categories of cases than in
      controls. Among different levels of bacillary load and genotypes, GG or G/- and G
      allele significantly supports the incidence of 2 + class for bacterial load.

PMID- 25572427
TI  - Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity
      of osteosarcoma cells to doxorubicin and cisplatin.
AB  - X-chromosome-linked inhibitor of apoptosis protein (XIAP) is an important member
      of the inhibitors of apoptosis (IAP) family. It has been shown that XIAP promotes
      the invasion, metastasis, growth and survival of malignant cells, and confers
      resistance to some chemotherapeutic drugs in various types of cancer. However,
      little is known regarding its detailed role in osteosarcoma (OS). In the present
      study, we first investigated the expression of XIAP in OS tissues, and an
      increased expression of XIAP in OS tissues compared to adjacent non-tumor tissue
      was identified. Additionally, its expression level correlated with key
      pathological characteristics including clinical stage, tumor size and metastasis.
      Subsequently, small interfering RNA (siRNA) was used to block XIAP expression to
      evaluate the effect of XIAP siRNA on cell proliferation, colony formation, cell
      cycle, apoptosis, tumorigenicity, and the combined effects of doxorubicin or
      cisplatin in OS cell lines (MG63 cells). Downregulation of XIAP expression using
      the RNA silencing approach efficiently decreased cell proliferation and colony
      formation, and induced cell apoptosis and cell cycle in the G0/G1 stage. In
      addition, this downregulation inhibited tumor growth in a nude murine model. The
      resuls also showed that treatment with XIAP-shRNA in combination with doxorubicin
      or cisplatin enhanced chemosensitivity. These results suggested that XIAP may aid
      the diagnosis of OS and may be an effective strategy for gene therapy of this
      disease.

PMID- 25572426
TI  - The impact of a home-based walking programme on falls in older people: the Easy
      Steps randomised controlled trial.
AB  - BACKGROUND: walking is the most popular form of exercise in older people but the
      impact of walking on falls is unclear. This study investigated the impact of a 48
      week walking programme on falls in older people. METHODS: three hundred and
      eighty-six physically inactive people aged 65+ years living in the community were
      randomised into an intervention or control group. The intervention group received
      a self-paced, 48-week walking programme that involved three mailed printed
      manuals and telephone coaching. Coinciding with the walking programme manual
      control group participants received health information unrelated to falls.
      Monthly falls calendars were used to monitor falls (primary outcome) over 48
      weeks. Secondary outcomes were self-reported quality of life, falls efficacy,
      exercise and walking levels. Mobility, leg strength and choice stepping reaction
      time were measured in a sub-sample (n = 178) of participants. RESULTS: there was
      no difference in fall rates between the intervention and control groups in the
      follow-up period (IRR = 0.88, 95% CI: 0.60-1.29). By the end of the study,
      intervention group participants spent significantly more time exercising in
      general, and specifically walking for exercise (median 1.69 versus 0.75 h/week, P
      < 0.001). CONCLUSION: our finding that a walking programme is ineffective in
      preventing falls supports previous research and questions the suitability of
      recommending walking as a fall prevention strategy for older people. Walking,
      however, increases physical activity levels in previously inactive older people.

PMID- 25572428
TI  - Chemo- and diastereoselectivities in the electrochemical reduction of maleimides.
AB  - The electrochemical cathodic reduction of cyclic imides (maleimides) to
      succinimides can be achieved chemoselectively in the presence of alkene, alkyne,
      and benzyl groups. The efficiency of the system was demonstrated by using a 3D
      electrode in a continuous flow reactor. The reduction of 3,4-dimethylmaleimides
      to the corresponding succinimides proceeds with a 3:2 diastereomeric ratio, which
      is independent of the nitrogen substituent and electrode surface area. The
      stereoselectivity of the process was rationalized by using DFT calculations,
      involving an acid-catalyzed tautomerization of a half-enol occurring through a
      double hydrogen-transfer mechanism. 

PMID- 25572429
TI  - Granulocyte colony-stimulating factor-induced granulomatous dermatitis with
      enlarged histiocytes clinically manifesting as painful edematous nodules with
      high fever similar to Sweet's syndrome.
AB  - A 72-year-old woman with a history of diffuse large B cell lymphoma and recent
      recurrence visited our department complaining of several painful edematous
      nodules with blisters on her face. She had iteratively developed cutaneous
      eruptions after every treatment with granulocyte colony-stimulating factor (G
      CSF) for neutropenia, and each time the eruption improved after the cessation of
      the G-CSF treatment. The blisters became crusty and the skin lesions slightly
      improved, but on the 24th hospital day, the eruption formed painful erythematous
      nodules with erosion, and the patient also developed a high fever of up to 38
      degrees C. A biopsy specimen showed a dermal infiltrate of increased and enlarged
      plump histiocytes, some of which indicated karyomitosis with a small number of
      lymphocytes. No increase in the number of eosinophils or neutrophils was noted.
      These eruptions lasted for 15 days and disappeared with the recovery of the
      peripheral blood count and attendant cessation of G-CSF. We diagnosed this case
      as G-CSF-induced granulomatous dermatitis with enlarged histiocytes. Several
      cases with maculopapular rash and dermal inflammatory infiltrate composed of
      interstitially arranged large histiocytes have been reported. However, to the
      best of our knowledge, this is the first case report of G-CSF-induced
      granulomatous dermatitis with enlarged histiocytes clinically manifesting as
      painful edematous nodules with a high fever, similar to Sweet's syndrome. We
      speculated that the infiltrating cells were not neutrophils but histiocytes,
      presumably because of agranulocytosis.

PMID- 25572430
TI  - Distinct intrinsic network connectivity patterns of post-traumatic stress
      disorder symptom clusters.
AB  - OBJECTIVE: Post-traumatic stress disorder (PTSD) is considered a multidimensional
      disorder, with distinct symptom clusters including re-experiencing,
      avoidance/numbing, hyperarousal, and most recently
      depersonalization/derealization. However, the extent of differing intrinsic
      network connectivity underlying these symptoms has not been fully investigated.
      We therefore investigated the degree of association between resting connectivity
      of the salience (SN), default mode (DMN), and central executive (CEN) networks
      and PTSD symptom severity. METHOD: Using resting-state functional MRI data from
      PTSD participants (n = 21), we conducted multivariate analyses to test whether
      connectivity of extracted independent components varied as a function of re
      experiencing, avoidance/numbing, hyperarousal, and
      depersonalization/derealization. RESULTS: Hyperarousal symptoms were associated
      with reduced connectivity of posterior insula/superior temporal gyrus within SN
      [peak Montreal Neurological Institute (MNI): -44, -8, 0, t = -4.2512, k = 40].
      Depersonalization/derealization severity was associated with decreased
      connectivity of perigenual anterior cingulate/ventromedial prefrontal cortex
      within ventral anterior DMN (peak MNI: 8, 40, -4; t = -3.8501; k = 15) and
      altered synchrony between two DMN components and between DMN and CEN. CONCLUSION:
      Our results are consistent with prior research showing intrinsic network
      disruptions in PTSD and imply heterogeneous connectivity patterns underlying PTSD
      symptom dimensions. These findings suggest possible biomarkers for PTSD and its
      dissociative subtype.

PMID- 25572432
TI  - Conflict of interest and transparency: are the headlights misaligned?

PMID- 25572431
TI  - Gradient-based delineation of the primary GTV on FLT PET in squamous cell cancer
      of the thoracic esophagus and impact on radiotherapy planning.
AB  - BACKGROUND: To validate a gradient-based segmentation method for gross tumor
      volume(GTV) delineation on (8)F-fluorothymidine (FLT)positron emission tomography
      (PET)/ computer tomography (CT) in esophageal squamous cell cancer through
      pathologic specimen, in comparison with standardized uptake values (SUV)
      threshold-based methods and CT. The corresponding impact of this GTV delineation
      method on treatment planning was evaluated. METHODS AND MATERIALS: Ten patients
      with esophageal squamous cell cancer were enrolled. Before radical surgery, all
      patients underwent FLT-PET/CT. GTVs were delineated by using four methods.
      GTVGRAD, GTV1.4 and GTV30%max were segmented on FLT PET using a gradient-based
      method, a fixed threshold of 1.4 SUV and 30% of SUVmax, respectively. GTVCT was
      based on CT data alone. The maximum longitudinal tumor length of each segmented
      GTV was compared with the measured tumor length of the pathologic gross tumor
      length (LPath). GTVGRAD, GTV1.4 and GTV30%max were compared with GTVCT by overlap
      index. Two radiotherapy plannings (planGRAD) and (planCT) were designed for each
      patient based on GTVGRAD and GTVCT. The dose-volume parameters for target volume
      and normal tissues, CI and HI of planGRAD and planCT were compared. RESULTS: The
      mean +/- standard deviation of LPath was 6.47 +/- 2.70 cm. The mean +/- standard
      deviation of LGRAD,L1.4, L30%max and LCT were 6.22 +/- 2.61, 6.23 +/- 2.80, 5.95
      +/- 2.50,7.17 +/- 2.28 cm, respectively. The Pearson correlation coefficients
      between LPath and each segmentation method were 0.989, 0.920, 0.920 and 0.862,
      respectively. The overlap indices of GTVGRAD, GTV1.4, GTV30%max when compared
      with GTVCT were 0.75 +/- 0.12, 0.71 +/- 0.12, 0.57 +/- 0.10, respectively. The
      V5, V10, V20, V30 and mean dose of total-lung,V30 and mean dose of heart of
      planGRAD were significantly lower than planCT. CONCLUSIONS: The gradient-based
      method provided the closest estimation of target length. The radiotherapy
      plannings based on the gradient-based segmentation method reduced the irradiated
      volume of lung, heart in comparison to CT.

PMID- 25572433
TI  - Relationship between functional end-to-end anastomosis for colon cancer and
      surgical site infections.
AB  - PURPOSE: Surgical site infections (SSI) are a common complication of
      gastrointestinal tract surgery. In this study, we explored the correlation
      between the anastomosis method and the incidence of SSI. METHODS: A total of 110
      patients underwent ileocecal resection or right hemicolectomy for the excision of
      colon cancer. Two methods (open and closed, 28 and 82 patients, respectively) of
      functional end-to-end anastomosis were adopted. RESULTS: Increased perioperative
      blood loss (p = 0.029214), a longer hospital stay (p = 0.026668) and the
      development of SSI (p = 0.000181) were significantly correlated with the open
      method. There was no correlation between SSI and the body mass index, or between
      SSI and the length of the surgery or diabetes mellitus. However, patients that
      developed SSI tended to be obese. CONCLUSION: The open method was associated with
      a higher incidence of SSI. Therefore, it is necessary to consider potential
      contamination of the surgical field at the time of anastomosis to reduce the
      incidence of SSI.

PMID- 25572436
TI  - The significance of combined CK5/6 and p63 immunohistochemistry in predicting the
      risks of subsequent carcinoma development in intraductal papilloma of the breast.
AB  - Prediction of subsequent risks of breast carcinoma (BC) development in
      intraductal papilloma (IDP) has remained controversial with the exception of
      atypical papilloma (AP). The potential value of immunohistochemistry (IHC) of
      cytokeratin 5/6 [CK5/6] and p63 have been proposed but its standardization has
      also remained controversial. We studied 17 patients initially diagnosed as IDP or
      AP who subsequently developed BC with 34 age-matched controls. We compared
      histological features, results of IHC (estrogen receptor [ER], progesterone
      receptor [PR], human epidermal growth factor receptor 2 [HER2], p63, CK5/6,
      Ki67), and ultrasound findings. Univariate conditional logistic regression
      analysis revealed that the status of both CK5/6 and p63/CK5/6 were significantly
      associated with subsequent BC development (P < 0.05). BC development in CK5/6
      positive patients was 17.9% and p63/CK5/6 double positive patients 8.6%,
      respectively. Ultrasound evaluation was not significantly associated with any of
      the parameters examined and subsequent carcinoma development. Despite CK5/6
      positivity, the subsequent incidence of BC development was nearly 20%. However
      p63/CK5/6 double positive status could predict a significantly lower subsequent
      carcinoma incidence, indicating a more accurate prognostic utility. Combining
      p63/CK5/6 with histological findings could be easily applied and could predict
      the subsequent BC development of the patients diagnosed as IDP at biopsy. 

PMID- 25572437
TI  - Groundwater Quality Modeling with a Small Data Set.
AB  - Seventeen groundwater quality variables collected during an 8-year period (2006
      to 2013) in Andimeshk, Iran, were used to implement an artificial neural network
      (NN) with the purpose of constructing a water quality index (WQI). The method
      leading to the WQI avoids instabilities and overparameterization, two problems
      common when working with relatively small data sets. The groundwater quality
      variables used to construct the WQI were selected based on principal component
      analysis (PCA) by which the number of variables were decreased to six. To fulfill
      the goals of this study, the performance of three methods (1) bootstrap
      aggregation with early stopping; (2) noise injection; and (3) ensemble averaging
      with early stopping was compared. The criteria used for performance analysis was
      based on mean squared error (MSE) and coefficient of determination (R(2) ) of the
      test data set and the correlation coefficients between WQI targets and NN
      predictions. This study confirmed the importance of PCA for variable selection
      and dimensionality reduction to reduce the risk of overfitting. Ensemble
      averaging with early stopping proved to be the best performed method. Owing to
      its high coefficient of determination (R(2)  = 0.80) and correlation coefficient
      (r=0.91), we recommended ensemble averaging with early stopping as an accurate NN
      modeling procedure for water quality prediction in similar studies. 

PMID- 25572435
TI  - AM841, a covalent cannabinoid ligand, powerfully slows gastrointestinal motility
      in normal and stressed mice in a peripherally restricted manner.
AB  - BACKGROUND AND PURPOSE: Cannabinoid (CB) ligands have been demonstrated to have
      utility as novel therapeutic agents for the treatment of pain, metabolic
      conditions and gastrointestinal (GI) disorders. However, many of these ligands
      are centrally active, which limits their usefulness. Here, we examine a unique
      novel covalent CB receptor ligand, AM841, to assess its potential for use in
      physiological and pathophysiological in vivo studies. EXPERIMENTAL APPROACH: The
      covalent nature of AM841 was determined in vitro using electrophysiological and
      receptor internalization studies on isolated cultured hippocampal neurons. Mouse
      models were used for behavioural analysis of analgesia, hypothermia and
      hypolocomotion. The motility of the small and large intestine was assessed in
      vivo under normal conditions and after acute stress. The brain penetration of
      AM841 was also determined. KEY RESULTS: AM841 behaved as an irreversible CB1
      receptor agonist in vitro. AM841 potently reduced GI motility through an action
      on CB1 receptors in the small and large intestine under physiological conditions.
      AM841 was even more potent under conditions of acute stress and was shown to
      normalize accelerated GI motility under these conditions. This compound behaved
      as a peripherally restricted ligand, showing very little brain penetration and no
      characteristic centrally mediated CB1 receptor-mediated effects (analgesia,
      hypothermia or hypolocomotion). CONCLUSIONS AND IMPLICATIONS: AM841, a novel
      peripherally restricted covalent CB1 receptor ligand that was shown to be
      remarkably potent, represents a new class of potential therapeutic agents for the
      treatment of functional GI disorders.

PMID- 25572439
TI  - Differentiation of 3T3-L1 preadipocytes is inhibited under a modified ceiling
      culture.
AB  - Ceiling culture is an inverted and closed cell culture system which represents a
      novel method for exploring adipocyte characteristics and function. Although the
      role of ceiling culture in mature adipocyte dedifferentiation has been
      extensively studied, its potential effects on preadipocyte differentiation remain
      unclear. In this study, we established a simplified dish ceiling culture method
      for 3T3-L1 preadipocytes and showed that our novel ceiling culture method could
      reproduce the function of the traditional flask ceiling culture. Then, we
      investigated the effects of ceiling culture on 3T3-L1 preadipocyte
      differentiation by Oil red O staining and RT-qPCR. The results showed that
      ceiling culture significantly impaired triglyceride accumulation and adipogenic
      marker genes expression in 3T3-L1 preadipocytes. These findings suggest that
      ceiling culture inhibited 3T3-L1 preadipocyte differentiation while inducing
      mature adipocytes dedifferentiation. Taken together, our data facilitate the
      understanding of the property of ceiling culture and promote the study of
      revealing the underlying mechanisms of mature adipocytes dedifferenatiation. 

PMID- 25572438
TI  - Redesign of process map to increase efficiency: Reducing procedure time in
      cervical cancer brachytherapy.
AB  - PURPOSE: To increase intraprocedural efficiency in the use of clinical resources
      and to decrease planning time for cervical cancer brachytherapy treatments
      through redesign of the procedure's process map. METHODS AND MATERIALS: A
      multidisciplinary team identified all tasks and associated resources involved in
      cervical cancer brachytherapy in our institution and arranged them in a process
      map. A redesign of the treatment planning component of the process map was
      conducted with the goal of minimizing planning time. Planning time was measured
      on 20 consecutive insertions, of which 10 were performed with standard procedures
      and 10 with the redesigned process map, and results were compared. Statistical
      significance (p < 0.05) was measured with a two-tailed t test. RESULTS: Twelve
      tasks involved in cervical cancer brachytherapy treatments were identified. The
      process map showed that in standard procedures, the treatment planning tasks were
      performed sequentially. The process map was redesigned to specify that contouring
      and some planning tasks are performed concomitantly. Some quality assurance tasks
      were reorganized to minimize adverse effects of a possible error on procedure
      time. Test dry runs followed by live implementation confirmed the applicability
      of the new process map to clinical conditions. A 29% reduction in planning time
      (p < 0.01) was observed with the introduction of the redesigned process map.
      CONCLUSIONS: A process map for cervical cancer brachytherapy was generated. The
      treatment planning component of the process map was redesigned, resulting in a
      29% decrease in planning time and a streamlining of the quality assurance
      process.

PMID- 25572441
TI  - A simple quantitative method to study protein-lipopolysaccharide interactions by
      using liquid crystals.
AB  - The interaction of proteins with endotoxins has divergent effects on
      lipopolysaccharide (LPS)-induced responses, which serve as a basis for many
      clinical and therapeutic applications. It is, therefore, important to understand
      these interactions from both theoretical and practical points of view. This paper
      advances the design of liquid crystal (LC)-based stimuli-responsive soft
      materials for quantitative measurements of LPS-protein binding events through
      interfacial ordering transition. Micrometer-thick films of LCs undergo easily
      visualized ordering transitions in response to proteins at LPS-aqueous interfaces
      of the LCs. The optical response of the LC changes from dark to bright after
      aqueous solutions of hemoglobin (Hb), bovine serum albumin (BSA), and lysozyme
      proteins (LZM) are in contact with a LPS-laden aqueous-LC interface. The effects
      of interactions of different proteins with LPS are also observed to cause the
      response of the LC to vary significantly from one to another; this indicates that
      manipulation of the protein-LPS binding affinity can provide the basis for a
      general, facile method to tune the LPS-induced responses of the LCs to
      interfacial phenomena. By measuring the optical retardation of the 4'-pentyl-4
      cyanobiphenyl (5CB) LC, the binding affinity of the proteins (Hb, BSA, and LZM)
      towards LPS that leads to different orientational behavior at the aqueous
      interfaces of the LCs can be determined. The interaction of proteins with the LPS
      laden monolayer is highest for LPS-Hb, followed by LPS-BSA, and least for LPS
      LZM; this is in correlation with their increasing order of binding constants (LPS
      Hb>LPS-BSA>LPS-LZM). The results presented herein pave the way for quantitative
      and multiplexed measurements of LPS-protein binding events and reveal the
      potential of the LC system to be used as quantitative LC-based, stimuli
      responsive soft materials. 

PMID- 25572442
TI  - In silico validation procedure for cell volume fraction estimation through
      dielectric spectroscopy.
AB  - Dielectric spectroscopy has proved to be a good tool for analyzing the passive
      electrical properties of biological tissues as well as those of inhomogeneous
      materials. This technique promises to be a valid alternative to the classical
      ones based on metabolites to monitor the growth and cell volume fraction of cell
      cultures in a simple and minimally invasive way. In order to obtain an accurate
      estimation of the cell volume fraction as a function of the permittivity of the
      suspension, a simple in silico procedure is proposed. The procedure is designed
      to perform homogenization from the micro-scale to the macro-scale using simple
      analytical models and simulation setups hypothesizing the properties of diluted
      suspension (cell volume fraction less than 0.2). Results obtained show the
      possibility to overcome some trouble involving the analytical treatment of the
      cellular shape by considering a sphere with the same permittivity in the
      quantitative analysis of the cell volume fraction. The entire study is based on
      computer simulations performed in order to verify the correctness of the
      procedure. Obtained data are used in a cell volume fraction estimation scenario
      to show the effectiveness of the procedure. 

PMID- 25572443
TI  - Characteristics of neck level VI lymph nodes in papillary thyroid carcinoma:
      correlation between nodal characteristics and primary tumor.
AB  - Little is known about the pathological characteristics of metastatic and
      nonmetastatic lymph nodes (LNs) in papillary thyroid carcinoma (PTC). The aim of
      this study was to elucidate the pathological characteristics of neck level VI
      nodes and correlations with clinicopathological parameters. We investigated the
      clinicopathological features of 124 classical PTCs and characteristics of 850
      dissected neck level VI LNs. Immunohistochemistry for nuclear factor-kappaB (NF
      kappaB) and Ki-67 was performed on primary tumors, and correlations with nodal
      characteristics were investigated. Nodal metastasis at neck level VI was
      identified in 68 of 124 PTCs (54.8 %) and was significantly correlated with tumor
      size, tumor multifocality, extrathyroidal extension, and tumor stage. LN
      metastasis was significantly correlated with larger mean LN size (P < 0.001),
      larger size of the largest LN (P < 0.001), and more LNs (P < 0.001). The mean
      size of metastatic LNs (n = 233) was significantly larger than nonmetastatic LNs
      (n = 617) (P < 0.001). Primary tumor diameter significantly correlated with the
      largest LN size (P = 0.014, R (2) = 0.049), but not mean size or number of LNs by
      linear regression analysis. NF-kappaB and Ki-67 proliferation indexes were not
      significantly correlated with larger nodal size. These results suggested that
      characteristics of nodes and primary tumor would be useful criteria for making
      decisions about preoperative surveillance of nodal metastasis.

PMID- 25572445
TI  - Nonradiative energy transfer in colloidal CdSe nanoplatelet films.
AB  - Nonradiative energy transfer (NRET) has been extensively studied in colloidal
      nanocrystal (quantum dots) and nanorod (quantum wires) assemblies. In this work,
      we present the first account of spectroscopic evidence of NRET in solid thin
      films of CdSe based colloidal nanoplatelets (NPLs), also known as colloidal
      quantum wells. The NRET was investigated as a function of the concentration of
      two NPL populations with different vertical thicknesses via steady state and time
      resolved spectroscopy. NRET takes place from the NPLs with smaller vertical
      thickness (i.e., larger band gap) to the ones with a larger vertical thickness
      (i.e., smaller band gap) with efficiency up to ~60%. Here, we reveal that the
      NRET efficiency is limited in these NPL solid film assemblies due to the self
      stacking of NPLs within their own population causing an increased distance
      between the donor-acceptor pairs, which is significantly different to previously
      studied colloidal quantum dot based architectures for nonradiative energy
      transfer. 

PMID- 25572446
TI  - Response to Maniatis' "Is a unified model of contrast and constancy possible?
      Reply to Gilchrist".

PMID- 25572444
TI  - Incorporation of image data from a previous examination in 3D serial MR imaging.
AB  - OBJECT: We aimed to demonstrate that follow-up scans in longitudinal examinations
      can be significantly accelerated by using images from previous scans as priors
      for constrained reconstruction. MATERIALS AND METHODS: In this work, we propose a
      method for incorporating a prior image to improve the reconstruction of a new
      acquisition with considerable k-space undersampling, which contains a two-level
      registration scheme with non-parametric transformation, an adaptive synthesis
      procedure, and a constrained reconstruction with weighted total variation
      constraint. The performance of the method is evaluated using simulations, as well
      as results from volunteer and patient examinations. RESULTS: In vivo experiments
      with both volunteers and patients show that incorporating a prior image into the
      constrained reconstruction produces many fewer reconstruction errors compared to
      the conventional reconstruction using only the highly undersampled k-space data.
      CONCLUSION: The redundant information in the prior image can be efficiently
      adopted to improve the reconstruction quality of the new acquisition. When
      maintaining the image quality, higher acceleration can be achieved with the
      incorporation of the prior image.

PMID- 25572447
TI  - Vision Research special issue on the "On-line Visual Control of Action".

PMID- 25572449
TI  - Montreal Cognitive Assessment for screening mild cognitive impairment: variations
      in test performance and scores by education in Singapore.
AB  - BACKGROUND: The Montreal Cognitive Assessment (MoCA) was developed as a screening
      instrument for mild cognitive impairment (MCI). We evaluated the MoCA's test
      performance by educational groups among older Singaporean Chinese adults. METHOD:
      The MoCA and Mini-Mental State Examination (MMSE) were evaluated in two
      independent studies (clinic-based sample and community-based sample) of MCI and
      normal cognition (NC) controls, using receiver operating characteristic curve
      analyses: area under the curve (AUC), sensitivity (Sn), and specificity (Sp).
      RESULTS: The MoCA modestly discriminated MCI from NC in both study samples (AUC =
      0.63 and 0.65): Sn = 0.64 and Sp = 0.36 at a cut-off of 28/29 in the clinic-based
      sample, and Sn = 0.65 and Sp = 0.55 at a cut-off of 22/23 in the community-based
      sample. The MoCA's test performance was least satisfactory in the highest (>6
      years) education group: AUC = 0.50 (p = 0.98), Sn = 0.54, and Sp = 0.51 at a cut
      off of 27/28. Overall, the MoCA's test performance was not better than that of
      the MMSE. In multivariate analyses controlling for age and gender, MCI diagnosis
      was associated with a <1-point decrement in MoCA score (eta(2) = 0.010), but
      lower (1-6 years) and no education was associated with a 3- to 5-point decrement
      (eta(2) = 0.115 and eta(2) = 0.162, respectively). CONCLUSION: The MoCA's ability
      to discriminate MCI from NC was modest in this Chinese population, because it was
      far more sensitive to the effect of education than MCI diagnosis.

PMID- 25572448
TI  - Heroin use promotes HCV infection and dysregulates HCV-related circulating
      microRNAs.
AB  - Hepatitis C virus (HCV) infection is common among injection drug users (IDUs).
      There is accumulating evidence that circulating microRNAs (miRNAs) are associated
      with HCV infection and disease progression. The present study was undertaken to
      determine the in vivo impact of heroin use on HCV infection and HCV-related
      circulating miRNA expression. Using the blood specimens from four groups of the
      study subjects (HCV-infected individuals, heroin users with/without HCV
      infection, and healthy volunteers), we found that HCV-infected heroin users had
      significantly higher viral load than HCV-infected non-heroin users (p = 0.0004).
      Measurement of HCV-related circulating miRNAs in plasma showed that miRs-122,
      141, 29a, 29b, and 29c were significantly increased in the heroin users with HCV
      infection, whereas miR-351, an HCV inhibitory miRNA, was significantly decreased
      in heroin users as compared to control subjects. Further investigation identified
      a negative correlation between the plasma levels of miR-29 family members and
      severity of HCV infection based on aspartate aminotransferase to platelet ratio
      index (APRI). In addition, heroin use and/or HCV infection also dysregulated a
      panel of plasma miRNAs. Taken together, these data for the first time revealed in
      vivo evidence that heroin use and/or HCV infection alter circulating miRNAs,
      which provides a novel mechanism for the impaired innate anti-HCV immunity among
      IDUs.

PMID- 25572451
TI  - Varenicline as a Cause of Suicidal Outcomes.
AB  - OBJECTIVE: Postmarketing analyses and case reports have associated varenicline
      use with suicidal behaviors. This article reviews postmarketing analyses, case
      reports, clinical trials, uncontrolled observational studies, controlled
      observational studies, and studies in smokers with psychiatric problems that have
      tested this association. METHOD: The author searched the literature for relevant
      reports via computer and other searches to undertake a qualitative, systematic
      review. RESULTS: Two pooled analyses of 10 and 17 placebo-controlled trials
      failed to find more suicidal outcomes in the varenicline condition. Seven large
      uncontrolled observational studies reported low rates of suicide outcomes in
      varenicline users (<0.1%), and 1 study reported a higher rate (6%). Five large
      controlled observational studies did not find more suicide outcomes in
      varenicline users than in those using prescribed bupropion or over-the-counter
      nicotine medications. Small placebo-controlled trials and observational studies
      of smokers with current psychiatric problems did not find varenicline was
      associated with suicidal outcomes. CONCLUSIONS: Among the more valid study
      designs (pooled analyses of placebo controlled trials or large controlled
      observational studies), there is consistent evidence that varenicline either does
      not cause increased suicide outcomes, or if it does, the effect is very small.
      Warnings to consumers and clinicians should reflect, not just the results of
      postmarketing studies, but the results of the more valid research designs.

PMID- 25572450
TI  - Response to Transdermal Selegiline Smoking Cessation Therapy and Markers in the
      15q24 Chromosomal Region.
AB  - INTRODUCTION: Current treatments for smoking cessation have limited efficacy. A
      potential pharmaceutical treatment for smoking cessation is selegiline, a
      selective and irreversible monoamine oxidase B inhibitor. A few clinical trials
      have been carried out using selegiline but the results have been mixed. We sought
      to determine if genetic markers in cholinergic loci in the 15q24 chromosomal
      region predict response to smoking cessation therapy with selegiline. METHODS: We
      performed an 8-week double-blind, placebo-controlled clinical trial of the
      selegiline transdermal system in heavy smokers, with follow-up at weeks 25 and
      52. Eight single nucleotide polymorphisms (SNPs) in the 15q24 region, which
      contains the genes for the nicotinic acetylcholine receptor subunits CHRNA5,
      CHRNA3, and CHRNB4, were investigated for association with treatment response.
      RESULTS: The CHRNB4 promoter SNP rs3813567 was associated with both point
      prevalence abstinence and post-quit craving. Carriers of the minor C allele
      treated with selegiline showed lower rates of abstinence and higher levels of
      craving than selegiline-treated non-carriers, indicating that the rs3813567 C
      allele adversely affects abstinence in selegiline-treated smokers. This effect
      was not present among placebo-treated smokers. Selegiline-treated smokers with
      the CHRNA5 rs680244 GG genotype had lower post-quit craving, and unlike placebo
      treated GG-carrying smokers, did not experience a post-quit increase in
      depressive symptoms. CONCLUSIONS: Variants in genes encoding cholinergic
      receptors affect abstinence, craving and mood in selegiline-treated smokers.
      Selegiline primarily affects dopamine levels in the brain, but cholinergic input
      affects nicotine-induced dopaminergic activity. These markers may have value in
      identifying those likely to respond to selegiline for smoking cessation.

PMID- 25572452
TI  - Determination of Melatonin in Rice (Oryza sativa) Grains by Pressurized Liquid
      Extraction.
AB  - Melatonin provides a number of benefits for human health. The study reported here
      concerns the optimization, validation, and application of analytical pressurized
      liquid extraction and high-performance liquid chromatography coupled to a
      fluorescence detector for the determination of melatonin in rice grains. The
      factors that are most likely to affect the extraction efficiency were optimized
      with a 2IV7-2 fractional factorial design. The optimum extraction conditions were
      achieved by applying 70% EtOAc in MeOH at 200  degrees C and 200 atm for a static
      time of 5 min in two cycles with 50% flushing and a 60 s purge to extract a 2.5 g
      rice sample. The method validation ensured excellent linearity, limit of
      detection, limit of quantification, precision, and recovery. Furthermore, the
      method was applied to various rice products composed of polished, whole grain,
      aromatic, black, black glutinous, red, and parboiled rice. All kinds of pigmented
      rice grains showed high levels of melatonin (>100 MUg kg -1), and the highest
      levels were found in red rice.

PMID- 25572453
TI  - Heart transplant outcomes in patients with left ventricular non-compaction
      cardiomyopathy.
AB  - BACKGROUND: Left ventricular non-compaction cardiomyopathy (LVNCC) is a rare
      disease that starts in utero and may progress to heart failure (HF), sometimes
      requiring orthotopic heart transplantation (OHT). There are limited data
      addressing characteristics of LVNCC patients that require OHT and their outcomes.
      We therefore sought to investigate the characteristics and outcomes of LVNCC
      patients treated with OHT. METHODS: We queried the United Network for Organ
      Sharing (UNOS) database for all patients listed for OHT with LVNCC as the primary
      heart failure etiology between 2000 and 2013. We examined their characteristics
      at listing and outcomes after OHT and compared the findings with those of
      patients with idiopathic cardiomyopathy (IDCMP). RESULTS: We identified 113
      patients (43 adults and 70 pediatrics) with LVNCC of 45,298 patients (0.25%
      overall, 0.11% of adults and 1.0% of pediatrics) listed for OHT in this time
      period. Most were male children with mean age at listing of 16.9 years. Compared
      with the overall IDCMP cohort, patients with LVNCC were younger, had higher use
      of inotropes and extracorporeal membrane oxygenation (ECMO), and were more often
      listed as UNOS Status 1A with shorter waiting time. However, when adjusted for
      age, gender and ethnicity, these differences disappeared. During transplant
      listing, 8 (7.9%) died, 5 (5.0%) improved and avoided transplant, 3 (3.0%) became
      too sick for transplant and 78 (77.2%) underwent OHT. There was a non-significant
      trend toward longer cardiac allograft survival in patients with LVNCC (10.6 vs.
      9.4 years; log-rank test, p = 0.068). Patients with LVNCC had similar outcomes to
      other IDCMP patients, except for more post-transplant infections (50.0% vs.
      21.6%, p < 0.05). CONCLUSIONS: LVNCC patients undergoing heart transplantation
      are mostly pediatric and predominantly bridged to transplant with inotropes or
      ECMO. Despite having more post-transplant infections, their survival is similar
      to that of other IDCMP patients.

PMID- 25572454
TI  - Clinical and molecular characterization of the 20q11.2 microdeletion syndrome:
      six new patients.
AB  - Interstitial microdeletions of 20q chromosome are rare, only 17 patients have
      been reported in the literature to date. Among them, only six carried a proximal
      20q11.21-q11.23 deletion, with a size ranging from 2.6 to 6.8 Mb. The existence
      of a 20q11.2 microdeletion syndrome has been proposed, based on five previously
      reported cases that displayed anomalies of the extremities, intellectual
      disability, feeding difficulties, craniofacial dysmorphism and variable
      malformations. To further characterize this syndrome, we report on six new
      patients with 20q11.2 microdeletions diagnosed by whole-genome array-based
      comparative genomic hybridization. These patient reports more precisely refined
      the phenotype and narrowed the minimal critical region involved in this syndrome.
      Careful clinical assessment confirms the distinctive clinical phenotype. The
      craniofacial dysmorphism consists of high forehead, frontal bossing,
      enophthalmos, and midface hypoplasia. We have identified a 1.62 megabase minimal
      critical region involved in this syndrome encompassing three genes-GDF5, EPB41L1,
      andSAMHD1-which are strong candidates for different aspects of the phenotype.
      These results support that 20q11.2 microdeletion syndrome is a new contiguous
      gene deletion syndrome with a recognizable phenotype.

PMID- 25572455
TI  - Biodistribution and anti-tumor efficacy of intratumorally injected necrosis-avid
      theranostic agent radioiodinated hypericin in rodent tumor models.
AB  - Hypericin has an excellent necrosis-specific targeting capacity; thus, we
      explored small-molecular tumor necrosis therapy (SMTNT) for inhibiting tumor
      growth in rodent tumor models. H22 and S180 tumor-bearing Kunming (KM) mice were
      intratumorally injected with (131)I-monoiodohypericin ((131)I-MIH) to investigate
      the biodistribution of (131)I-MIH as a function of time. Single-photon emission
      computed tomography (SPECT), autoradiography, fluorescence microscopy and
      hematoxylin and eosin (H&E) staining were performed to determine the intra
      tumoral distribution of (131)I-MIH. A therapeutic evaluation study was also
      performed in the tumor-bearing KM mice using saline and a positive drug as
      controls. Gamma counting, SPECT images, autoradiography and fluorescence
      microscopy and H&E staining results revealed intense retention of (131)I-MIH in
      the necrotic tumor over 168 h and good in vivo stability of the agent. Therapy
      with a single dose of intra-tumoral administration of (131)I-MIH caused
      significant tumor growth delay. A histopathological analysis of the tumors and
      normal organs further validated the therapeutic efficacy and limited systemic
      toxicity of (131)I-MIH. The prolonged tumor retention and effective therapy
      indicated that (131)I-MIH may be a promising intratumorally injected SMTNT agent.

PMID- 25572456
TI  - Delivery of anti-microRNA-21 antisense-oligodeoxynucleotide using amphiphilic
      peptides for glioblastoma gene therapy.
AB  - Inhibition of microRNA-21 (miR-21) has been shown to promote apoptosis of cancer
      cells and to reduce tumor size in glioblastoma. However, efficient carriers for
      antisense-oligodeoxynucleotide (antisense-ODN) against miR-21 have not yet been
      developed. In this study, the R3V6 peptide (R3V6) was evaluated as a carrier of
      antisense-ODN. In a gel retardation assay, R3V6 formed a complex with an
      antisense-ODN. The serum stability assay showed that R3V6 protected it from
      nucleases more efficiently than polyethylenimine (PEI; 25 kDa, PEI25k). A Renilla
      luciferase gene with a 3'-untranslated region (3'-UTR) recognizable by miR-21
      (psiCHECK2-miR-21-UTR) was constructed for the antisense-ODN assay. psiCHECK2-miR
      21-UTR expressed less Renilla luciferase in the cells with a higher level of miR
      21 due to the effect of miR-21. In an in vitro transfection assay, the R3V6
      peptide delivered anti-miR-21 antisense-ODN into cells more efficiently than PEI
      (25 kDa, PEI25k) and lipofectamine. As a result, antisense-ODN/R3V6 complex
      inhibited miR-21 and increased Renilla luciferase expression more efficiently
      than antisense-ODN/PEI25k or antisense-ODN/Lipofectamine complexes in both C6 and
      A172 glioblastoma cells. Furthermore, the antisense-ODN/R3V6 complexes reduced
      the level of miR-21 and induced apoptosis of glioblastoma cells. These results
      suggest that the R3V6 peptide may be a useful carrier of antisense-ODN for
      glioblastoma gene therapy. 

PMID- 25572457
TI  - Food neophobia in wild and laboratory rats (multi-strain comparison).
AB  - Although empirical studies comparing neophobia in wild and laboratory rats have
      been conducted in the past, a few decades have passed since most of them were
      completed. This is a substantial period of time in the case of fast-breeding
      animals such as rats. Equally important are the inconsistencies in research
      findings with respect to comparisons between wild and laboratory rats, and within
      domesticated strains. As well as having the aim of updating knowledge of
      neophobia among different types of rats, the present experiment was also an
      attempt to isolate a specific fear of a new food from a general fear of a novel
      object. The procedure was that rats accustomed to one type of food served in a
      specific location and in a familiar container were given a different type of
      food. Test trials were preceded by food deprivation. The following variables were
      measured: feeding latency, the pace of eating, the number of approaches to the
      container, and the number of times food was sampled in each trial. The amount of
      food consumed in each trial was weighed and also taken into account. Grooming
      time served as the measure of stress among the rats in the experiment. The
      results of the experiment did not confirm the assertion of some authors that wild
      rats avoid eating unfamiliar foods. All groups demonstrated only a temporary
      decrease in the amount of food consumed, the magnitude of which was similar in
      all strains. No evidence of particularly low neophobia in albino rats was found.
      However, the behavioral symptoms indicated higher levels of stress in wild rats
      compared to the other groups. 

PMID- 25572458
TI  - Five on one side: personal and social information in spatial choice.
AB  - To examine whether the outcome of a rat's own choices ("personal information")
      and the choice behavior of another rat ("social information") can jointly control
      spatial choices, rats were tested in an open field task in which they searched
      for food. For the rats of primary interest (Subject Rats), the baited locations
      were all on one side of the arena, but the specific locations baited and the side
      on which they occurred varied over trials. The Subject Rats were sometimes tested
      together with an informed "Model" rat that had learned to find food in the same
      five locations (all on the same side of the arena) on every trial. Unintended
      perceptual cues apparently controlled spatial choices at first, but when
      perceptual cues to food location were not available, choices were controlled by
      both personal information (allowing the baited side of the arena to be
      determined) and social information (allowing baited locations to be determined
      more precisely). This shows that control by personal and social information are
      not mutually exclusive and supports the view that these two kinds of information
      can be used flexibly and adaptively to guide spatial choices. This article is
      part of a Special Issue entitled: tribute to Tom Zentall. 

PMID- 25572459
TI  - Branched polyethylenimine improves hydrogen photoproduction from a CdSe quantum
      dot/[FeFe]-hydrogenase mimic system in neutral aqueous solutions.
AB  - Nature uses hydrogenase enzyme to catalyze proton reduction at pH 7 with
      overpotentials and catalytic efficiencies that rival platinum electrodes. Over
      the past several years, [FeFe]-hydrogenase ([FeFe]-H2 ase) mimics have been
      demonstrated to be effective catalysts for light-driven H2 evolution. However, it
      remains a significant challenge to realize H2 production by such an artificial
      photosynthetic system in neutral aqueous solution. Herein, we report a new system
      for photocatalytic H2 evolution working in a broad pH range, especially under
      neutral conditions. This unique system is consisted of branched polyethylenimine
      (PEI)-grafted [FeFe]-H2 ase mimic (PEI-g-Fe2 S2 ), MPA-CdSe quantum dots
      (MPA=mercaptopropionic acid), and ascorbic acid (H2 A) in water. Due to the
      secondary coordination sphere of PEI, which has high buffering capacity and
      stabilizing ability, the system is able to produce H2 under visible-light
      irradiation with turnover number of 10 600 based on the Fe2 S2 active site in PEI
      g-Fe2 S2 . The stability and activity are much better than that of the same
      system under acidic or basic conditions and they are, to the best of our
      knowledge, the highest known to date for photocatalytic H2 evolution from a
      [FeFe]-H2 ase mimic in neutral aqueous solution.

PMID- 25572460
TI  - Evaluating a Web-Based Educational Module on Oral Cancer Examination Based on a
      Behavioral Framework.
AB  - Patients at risk of developing oral and/or oropharyngeal cancer (OPC) are more
      likely to see primary care providers (PCPs) than a dentist. Many PCPs do not
      regularly perform oral cancer examination (OCE). The purpose of this study was to
      design a web-based educational program based on a behavioral framework to
      encourage PCPs to conduct OCE. PCPs were solicited to provide feedback on the
      program and to evaluate their short-term knowledge. The integrated behavioral
      model was used to design the program. Fifteen PCPs (five in each group:
      physicians, physician assistants, and nurse practitioners) reviewed the program
      and took a posttest: (1) index of knowledge of risk factors for oral cancer
      (RiskOC) and (2) index of knowledge of diagnostic procedures for oral cancer
      (DiagOC). Findings from the process evaluation were mainly positive, with
      comments on the length of the program comprising the ten negative comments. No
      significant difference among groups of PCPs (physicians, physician assistants,
      and nurse practitioners) was detected for DiagOC (p = 0.43) or RiskOC (p =
      0.201). A program on OPC for PCPs should be less than 40 min. Postviewing
      knowledge outcomes were similar for all PCPs. The web-based program on OPC based
      on a behavioral framework could have similar short-term knowledge outcomes for
      all PCPs and may increase the number of PCPs performing OCEs.

PMID- 25572461
TI  - Older Adult Health in Alabama's Black Belt Region.
AB  - Health issues are a concern in Alabama's Black Belt region, which runs across the
      southwestern part of the state and includes some of the poorest counties in the
      USA. As part of a Center for Disease Control (CDC)-sponsored study, we collected
      data covering several cancer (e.g., prostate, breast, skin) and other health
      related indicators (e.g., stress, insurance, stroke, heart disease) from 647
      predominantly African-American adults over the age of 50 in 20 communities in 7
      Black Belt counties in 2005 and 2006. Here, we provide an account of the state of
      the health of older African-Americans and compare their outcomes to those of
      their White counterparts in the region. African-Americans report having generally
      lower levels of health and were less apt to have a cancer history (ps<0.05) than
      the Whites in the region. Gender differences with respect to BMIs and smoking are
      also evident, with women having higher BMIs but lower levels of smoking.
      Physicians and researchers covering or interested in generally impoverished rural
      areas may find our results useful for comparative purposes.

PMID- 25572462
TI  - Development and Evaluation of Patient Education Materials for Elderly Lung Cancer
      Patients.
AB  - Patients treated for lung cancer are often elderly presenting a unique challenge
      for developing patient education materials. This study developed and evaluated a
      patient education pamphlet on lung stereotactic body radiotherapy (SBRT) designed
      specifically for an elderly population. The SBRT pamphlet was developed using a
      participatory design involving a convenience sample of patients. This prospective
      study assessed patient's opinions of pamphlet effectiveness through self-report
      questionnaires. The pamphlet was deemed "effective" if patients rated 16/18
      evaluation statements as "strongly agree" or "agree." Demographic data and health
      literacy (Rapid Estimate of Adult Literacy in Medicine short-form (REALM-SF))
      were also assessed. Patient opinion of pamphlet "effectiveness" was compared
      between patients with REALM-SF scores of 7 versus <7 using Fisher's exact test.
      The overall EQ-5D-5L score was compared for patients who did and did not find the
      pamphlet effective using the Wilcoxon-Mann-Whitney test. Thirty-seven patients
      participated. The median age was 76 years (range 56-93) and 22 patients (59 %)
      had <=high school education. Most patients preferred to have verbal (65 %) or
      written (78 %) educational materials as opposed to online information or
      educational classes. Thirty-two patients (86 %) rated the pamphlet as effective.
      The proportion of patients who found the pamphlet effective was 85.7 versus 86.7
      % (p = 1.00) in those with REALM 7 versus <7. The mean EQ-5D score was 67.5 (SD
      19.1) versus 71.8 (SD 8.7) (p = 0.84) in those who found the pamphlet effective
      versus not. Participatory design is an effective method for developing education
      materials for challenging patient groups such as elderly patients. Despite
      advanced age and comorbidity, this patient group had adequate health literacy.

PMID- 25572463
TI  - Latino Parents' Awareness and Receipt of the HPV Vaccine for Sons and Daughters
      in a State with Low Three-Dose Completion.
AB  - Latinos suffer a disproportionate burden of human papillomavirus (HPV)
      preventable cancers, yet uptake and completion of the HPV vaccine among Latinos
      is below recommendations. Reasons for low HPV vaccine uptake among Latinos in
      Utah are unknown. We surveyed Latino parents of HPV vaccine age-eligible
      adolescents (N=118). Univariable analyses identified sociodemographic
      characteristics associated with HPV vaccine awareness, interest, and uptake for
      daughter(s) and/or son(s) using chi-square tests or Fisher's exact tests. More
      parents who had lived in the USA for 15 years or more had vaccinated their
      daughter (43.6 vs. 32.5%, p=0.035) compared to those living in the USA for
      shorter time periods. Parents born in Mexico reported their son had not received
      the HPV vaccine (74.6 vs. 58.3%, p=0.049) more than those born elsewhere. Parents
      with Mexican birthplace and ancestry reported not knowing about the HPV vaccine
      as the main barrier to vaccinating daughters (47.1 vs. 5.9%, p=0.002 for both)
      and sons (birthplace 38.3 vs. 10.3%, p=0.007; ancestry 37.1 vs. 11.1%, p=0.013)
      compared to those born or descending elsewhere. Non-acculturated parents with a
      son were more likely to report not knowing about the HPV vaccine as the main
      barrier to vaccine receipt (47.6 vs. 12.5%, p<0.001). Our results focus on
      Latinos in an understudied region and complement prior research in other regions.
      This study may have implications for designing culturally tailored interventions
      to improve uptake of the HPV vaccine among the growing population of Latinos in
      Utah, and other states in the Intermountain West.

PMID- 25572464
TI  - VEGF-A inhibition ameliorates podocyte apoptosis via repression of activating
      protein 1 in diabetes.
AB  - BACKGROUND/AIMS: Vascular endothelial growth factor-A (VEGF-A) upregulation and
      podocyte apoptosis have been documented in diabetes. This study was designed to
      investigate whether inhibiting VEGF-A could ameliorate podocyte apoptosis in
      diabetes and the underlying mechanisms. METHODS: In vitro, small interfering RNAs
      (siRNAs) of VEGF-A and activator protein 1 (AP-1, c-fos and c-jun), bevacizumab
      (VEGF-A inhibitor) and SP600125 (AP-1 inhibitor) were added to high glucose (30
      mM) induced podocytes. Luciferase reporter assay was used to investigate whether
      AP-1 was a direct target of VEGF-A. In vivo, bevacizumab and SP600125 were
      administered to 12-week-old streptozotocin-induced male Sprague Dawley rats. The
      level of VEGF-A, c-fos, c-jun and bcl-2 were examined using immunostaining and
      Western blot analysis. Podocyte apoptosis was detected using the terminal
      deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end
      labeling (TUNEL) assay, electron microscopy and flow cytometry. RESULTS:
      Silencing VEGF-A or AP-1 upregulated bcl-2 and ameliorated podocyte apoptosis.
      Silencing VEGF-A decreased the level of c-fos and c-jun and bevacizumab and
      SP600125 treatment attenuated podocyte apoptosis. Luciferase reporter activity of
      VEGF-A-3'-UTR constructs was significantly provoked when stimulated with TGF
      beta1. In diabetic rat kidneys, VEGF-A co-localized with bcl-2 in podocytes. With
      bevacizumab and SP600125 treatment, the level of VEGF-A and AP-1 decreased while
      bcl-2 increased. Podocyte apoptotic rate was reduced with condensed podocyte
      nuclei less frequently observed. The urine albumin excretion rate (UAER) and
      albumin/creatinine were improved. CONCLUSION: This study demonstrates VEGF-A
      inhibition ameliorates podocyte apoptosis by regulating AP-1 and bcl-2 signaling.
      AP-1 is a direct target of VEGF-A and a novel player in podocyte apoptosis.

PMID- 25572466
TI  - Chemoprophylaxis Use and Risk of Venous Thromboembolism and Death in Adult
      Patients following Orthotopic Liver Transplantation.
AB  - BACKGROUND: Coagulation abnormalities in end-stage liver disease may preclude
      patients from receiving venous thromboembolism (VTE) prophylaxis immediately
      following orthotopic liver transplantation. METHODS: To identify risk factors for
      VTE and death following liver transplantation, a retrospective chart review was
      conducted in adult liver transplant recipients from January 1, 2001, to October
      1, 2011. RESULTS: In 716 transplantations in 701 patients, the overall incidence
      of VTE was 2.1%. The incidence was 3.6% in patients who received chemoprophylaxis
      compared to 1.4% in those without chemoprophylaxis (P = .06). Most patients
      (69.5%) did not receive chemoprophylaxis postsurgery during their
      hospitalization. Multivariate logistic regression modeling revealed no
      association between the use of chemoprophylaxis (adjusted odds ratio [OR] 1.5
      [0.45-4.7], P = .53) and VTE. A significant positive association was observed
      between the use of chemoprophylaxis (adjusted OR 3.2 [1.3-8.0], P = .01) and
      death. CONCLUSION: Use of chemoprophylaxis and increasing amounts of blood
      products following orthotopic liver transplant was associated with increased
      mortality. A significant positive association was observed between blood product
      administration and VTE, while chemoprophylaxis use was not significantly
      associated with VTE. Larger prospective studies are necessary to further examine
      the significance of this finding.

PMID- 25572465
TI  - Psychiatric services: a platform for MTM.
AB  - Deinstitutionalization in the 1960s shifted the care of the mentally ill from
      state-funded institutions to community settings. Unfortunately, funding to
      support the treatment needs of this population has continued to be minimized, and
      countless individuals have not received much needed care. This has resulted in a
      large increase in mentally ill patients surfacing in jails, homeless shelters,
      and emergency departments. Subsequently, the federal government has begun to
      prioritize funding to address the mental health needs of our communities.
      Pharmacists are in a unique position to influence treatment outcomes for patients
      with mental illnesses, and the current state of health reform provides avenues
      for the pharmacist to become an essential part of the health care delivery team
      in numerous ambulatory care clinical settings. The challenges with adherence,
      medical and psychiatric comorbidities, polypharmacy with psychotropics, potential
      for life-threatening adverse effects, and the ever-present need for patient
      education are but a few reasons why pharmacists can be utilized to provide
      Medication Therapy Management services for these patients. 

PMID- 25572467
TI  - Catalyst-loaded porous WO3 nanofibers using catalyst-decorated polystyrene
      colloid templates for detection of biomarker molecules.
AB  - Pore-loaded WO3 nanofibers (NFs) functionalized with spherical catalyst films
      were achieved via electrospinning combined by the sacrificial templating route
      using layer-by-layer (LbL) catalyst assembled polystyrene (PS) colloids. The
      catalyst-loaded porous WO3 NFs exhibited significantly improved toluene and
      acetone detection capability for potential application in exhaled breath
      analysis. 

PMID- 25572468
TI  - Pannexin-1 silencing inhibits the proliferation of U87-MG cells.
AB  - Pannexin-1 (Panx-1) is abundantly expressed in vertebrates and has been shown to
      assemble into high-conductance single-membrane channels, which are permeable to
      large molecules and regulate cellular function. However, the association between
      Panx-1 and astrocyte proliferation is poorly understood. This study provides
      evidence for a difference in cell proliferation between wild-type and Panx-1
      knockdown cells. Proliferation of the U87-MG malignant glioma cell line was
      reduced following transfection with Panx-1-short interfering RNA. In addition,
      treatment with the Panx-1 activator, adenosine triphosphate, significantly
      reduced cell proliferation at 48 h in Panx-1-knockdown cells compared with wild
      type cells. In conclusion, on the basis of the present findings, Panx-1 is likely
      to be important in the regulation of U87-MG cell proliferation. This provides
      further support for the hypothesis that there is a correlation between Panx-1
      expression and U87-MG cell proliferation.

PMID- 25572469
TI  - BBCA: Improving the scalability of *BEAST using random binning.
AB  - BACKGROUND: Species tree estimation can be challenging in the presence of gene
      tree conflict due to incomplete lineage sorting (ILS), which can occur when the
      time between speciation events is short relative to the population size. Of the
      many methods that have been developed to estimate species trees in the presence
      of ILS, *BEAST, a Bayesian method that co-estimates the species tree and gene
      trees given sequence alignments on multiple loci, has generally been shown to
      have the best accuracy. However, *BEAST is extremely computationally intensive so
      that it cannot be used with large numbers of loci; hence, *BEAST is not suitable
      for genome-scale analyses. RESULTS: We present BBCA (boosted binned coalescent
      based analysis), a method that can be used with *BEAST (and other such co
      estimation methods) to improve scalability. BBCA partitions the loci randomly
      into subsets, uses *BEAST on each subset to co-estimate the gene trees and
      species tree for the subset, and then combines the newly estimated gene trees
      together using MP-EST, a popular coalescent-based summary method. We compare time
      restricted versions of BBCA and *BEAST on simulated datasets, and show that BBCA
      is at least as accurate as *BEAST, and achieves better convergence rates for
      large numbers of loci. CONCLUSIONS: Phylogenomic analysis using *BEAST is
      currently limited to datasets with a small number of loci, and analyses with even
      just 100 loci can be computationally challenging. BBCA uses a very simple divide
      and-conquer approach that makes it possible to use *BEAST on datasets containing
      hundreds of loci. This study shows that BBCA provides excellent accuracy and is
      highly scalable.

PMID- 25572471
TI  - Tendon lengthening and transfer.
AB  - Tendon lengthening and transfer are usually indicated for certain neuromuscular
      disorders, peripheral or central nerve injury, congenital disorder or direct
      traumatic or degenerative musculotendinous lesion. In musculotendinous
      lengthening, technique depends on muscle anatomy, degree of correction required,
      and the need to avoid excessive loss of force. Lengthening within the muscle or
      aponeurosis is stable. In the tendon, however, it may provide greater gain but is
      not stable and requires postoperative immobilization to avoid excessive
      lengthening. Tendon transfer consists in displacing a muscle's tendon insertion
      in order to restore function. The muscle to be transferred is chosen according to
      strength, architecture and course, contraction timing, intended direction,
      synergy and the joint moment arm to be restored. Functions to be restored have to
      be prioritized, and alternatives to transfer should be identified. The principles
      of tendon transfer require preoperative assessment of the quality of the tissue
      through which the transfer is to pass and of the suppleness of the joints
      concerned. During the procedure, transfer tension should be optimized and the
      neurovascular bundle should be protected. The method of fixation, whether tendon
      to-bone or tendon-to-tendon suture, should be planned according to local
      conditions and the surgeon's experience. 

PMID- 25572470
TI  - Multiple factors influencing the incidence of congenital hypothyroidism detected
      by neonatal screening.
AB  - BACKGROUND/AIMS: Over the years a rise in the incidence of congenital
      hypothyroidism (CH) has been described worldwide. The aim of our study was to
      investigate trends in the incidence of CH in Italy over the period 1987-2008, and
      to investigate which factors may have influenced the CH incidence in our country.
      METHODS: Data were derived from the Italian National Registry of Infants with
      Congenital Hypothyroidism. Since 1998 the laboratory procedures related to
      neonatal screening for CH have changed drastically. Accordingly, we estimated the
      CH incidence during the period 1987-1998 (period 1) and the period 1999-2008
      (period 2). RESULTS: The incidence of CH confirmed at birth (including transient
      hypothyroidism) has increased from 1:3,000 liveborn infants in period 1 to
      1:1,940 in period 2 (+54%), whereas the incidence of purely permanent CH
      increased from 1:3,200 to 1:2,320 (+38%). Lowering of the TSH cutoff was the most
      important factor contributing to the increase of CH incidence in Italy. Moreover,
      an increment of 58% of preterm babies with permanent CH was found in period 2
      compared with period 1. CONCLUSION: Our results suggest that more than one cause
      is responsible for the rise in the increasing CH incidence, with lowering of the
      screening TSH cutoff and an increased survival rate of a growing number of
      preterm babies both playing an important role.

PMID- 25572474
TI  - Could PD-L1 prove to be an effective therapeutic target for bladder cancer?

PMID- 25572472
TI  - A novel cofactor-binding mode in bacterial IMP dehydrogenases explains inhibitor
      selectivity.
AB  - The steadily rising frequency of emerging diseases and antibiotic resistance
      creates an urgent need for new drugs and targets. Inosine 5'-monophosphate
      dehydrogenase (IMP dehydrogenase or IMPDH) is a promising target for the
      development of new antimicrobial agents. IMPDH catalyzes the oxidation of IMP to
      XMP with the concomitant reduction of NAD(+), which is the pivotal step in the
      biosynthesis of guanine nucleotides. Potent inhibitors of bacterial IMPDHs have
      been identified that bind in a structurally distinct pocket that is absent in
      eukaryotic IMPDHs. The physiological role of this pocket was not understood.
      Here, we report the structures of complexes with different classes of inhibitors
      of Bacillus anthracis, Campylobacter jejuni, and Clostridium perfringens IMPDHs.
      These structures in combination with inhibition studies provide important
      insights into the interactions that modulate selectivity and potency. We also
      present two structures of the Vibrio cholerae IMPDH in complex with IMP/NAD(+)
      and XMP/NAD(+). In both structures, the cofactor assumes a dramatically different
      conformation than reported previously for eukaryotic IMPDHs and other
      dehydrogenases, with the major change observed for the position of the NAD(+)
      adenosine moiety. More importantly, this new NAD(+)-binding site involves the
      same pocket that is utilized by the inhibitors. Thus, the bacterial IMPDH
      specific NAD(+)-binding mode helps to rationalize the conformation adopted by
      several classes of prokaryotic IMPDH inhibitors. These findings offer a potential
      strategy for further ligand optimization. 

PMID- 25572475
TI  - Leishmania infantum FML pulsed-dendritic cells induce a protective immune
      response in murine visceral leishmaniasis.
AB  - AIM: To investigate the efficacy of FML loaded dendritic cells (DCs) in
      protection against visceral leishmaniasis. MATERIALS & METHODS: Mice were
      immunized with FML- or soluble Leishmania antigen-loaded DCs as well as FML or
      soluble Leishmania antigen in saponin and challenged with parasite. The levels of
      cytokines before and after challenge were detected by ELISA. Parasite burden
      (total Leishman-Donovan unit) was determined after parasite challenge. RESULTS:
      FML-saponin induced the highest IFN-gamma/IL-4 ratio among vaccinated groups,
      though this ratio was higher in FML-loaded DCs group subsequent to challenge with
      Leishmania infantum. Moreover, the greatest reduction in parasite number was
      detected in mice vaccinated with FML-loaded DCs compared with phosphate-buffered
      saline-treated mice (p = 0.002). CONCLUSION: FML-loaded DCs are one of the
      promising tools for protection against murine visceral leishmaniasis.

PMID- 25572473
TI  - Expression of nociceptive ligands in canine osteosarcoma.
AB  - BACKGROUND: Canine osteosarcoma (OS) is associated with localized pain as a
      result of tissue injury from tumor infiltration and peritumoral inflammation.
      Malignant bone pain is caused by stimulation of peripheral pain receptors, termed
      nociceptors, which reside in the localized tumor microenvironment, including the
      periosteal and intramedullary bone cavities. Several nociceptive ligands have
      been determined to participate directly or indirectly in generating bone pain
      associated with diverse skeletal abnormalities. HYPOTHESIS: Canine OS cells
      actively produce nociceptive ligands with the capacity to directly or indirectly
      activate peripheral pain receptors residing in the bone tumor microenvironment.
      ANIMALS: Ten dogs with appendicular OS. METHODS: Expression of nerve growth
      factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized
      in OS cell lines and naturally occurring OS samples. In 10 dogs with OS,
      circulating concentrations of nociceptive ligands were quantified and correlated
      with subjective pain scores and tumor volume in patients treated with
      standardized palliative therapies. RESULTS: Canine OS cells express and secrete
      nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS
      samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs,
      circulating nociceptive ligand concentrations were detectable but failed to
      correlate with pain status. Localized foci of nerve terminal proliferation were
      identified in a minority of primary bone tumor samples. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Canine OS cells express nociceptive ligands, potentially permitting
      active participation of OS cells in the generation of malignant bone pain.
      Specific inhibitors of nociceptive ligand signaling pathways might improve pain
      control in dogs with OS.

PMID- 25572476
TI  - Potent anti-prostate cancer immune response induced by dendritic cells transduced
      with recombinant adenoviruses encoding 4-1BBL combined with cytokine-induced
      killer cells.
AB  - AIM: To test the effect of dendritic cells (DCs) transduced with recombinant
      adenoviruses encoding 4-1BBL combined with cytokine-induced killer cells (CIKs)
      against prostate cancer. METHOD: Flow cytometry was used to detect the surface
      markers of the co-cultured cells, and cytotoxicity against prostate cancer cells
      in vitro as well as antitumor activities in vivo were observed. RESULTS: Our
      results showed that Ad-4-1BBL-transduced DCs could increase percentage of
      CD3(+)CD56(+) cells in CIKs, and CIKs co-cultured with Ad-4-1BBL-transduced DCs
      could augment the secretion of IL-12 and IFN-gamma and decrease TGF-beta
      production. In addition, Ad-4-1BBL-transduced DCs enhanced the cytotoxicity of
      CIKs against prostate cancer and resulted in inhibition of tumor growth and tumor
      bearing animals' survival. CONCLUSION: These results demonstrate that 4-1BBL
      engineered DCs can improve CIKs cytotoxicity against prostate cancer cells.

PMID- 25572478
TI  - Emerging immunotherapy and strategies directly targeting B cells for the
      treatment of diffuse large B-cell lymphoma.
AB  - During the last decade, significant prolonged survival in diffusive large B-cell
      lymphoma (DLBCL) has been observed. The efficacy of initial treatment improved
      mostly due to addition of a chimeric anti-CD20 monoclonal antibody (rituximab) to
      standard chemotherapeutic regimens. Moreover, accurate understanding of DLBCL
      pathogenesis and remarkable progress in gene expression profiling have led to the
      development of a variety of tumor-specific regimens. Novel agents target directly
      the pathways involved in signal transduction, lead to apoptosis and cancer cells
      differentiation. In this article, we mainly focus on new treatment options, such
      as monoclonal antibodies, tyrosine kinase inhibitors and immunomodulatory drugs,
      currently investigated in aggressive B-cell lymphoma with particular attention to
      DLBCL type. 

PMID- 25572479
TI  - Predictors of outcome in reduced intensity allogeneic hematopoietic cell
      transplantation for chronic lymphocytic leukemia: summarizing the evidence and
      highlighting the limitations.
AB  - Several studies have reported the prognostic significance of various clinical,
      genetic, biologic and molecular markers on postallogeneic hematopoietic cell
      transplantation outcomes such as nonrelapse mortality, relapse and survival.
      Notwithstanding limitations, existence of refractory/progressive disease at
      allografting yields worse nonrelapse mortality, more relapse and inferior overall
      survival. Advanced age results in higher nonrelapse mortality and increased
      relapse risk. Presence of poor-risk cytogenetics increases post-transplant
      relapse risk, but its impact on overall survival appears controversial.
      Developing prognostic models using large multicenter data could help better
      understand the effect of these and other variables on post-transplant outcomes.
      Newly discovered mutations as well as response (or not) to new potent therapies,
      such as ibrutinib or others, would likely be incorporated in such models. 

PMID- 25572477
TI  - Adoptive cell therapy for sarcoma.
AB  - Current therapy for sarcomas, though effective in treating local disease, is
      often ineffective for patients with recurrent or metastatic disease. To improve
      outcomes, novel approaches are needed and cell therapy has the potential to meet
      this need since it does not rely on the cytotoxic mechanisms of conventional
      therapies. The recent successes of T-cell therapies for hematological
      malignancies have led to renewed interest in exploring cell therapies for solid
      tumors such as sarcomas. In this review, we will discuss current cell therapies
      for sarcoma with special emphasis on genetic approaches to improve the effector
      function of adoptively transferred cells. 

PMID- 25572481
TI  - Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells
      over a 2-week period.
AB  - Previous works have shown that differentiated human HepaRG cells can exhibit drug
      metabolism activities close to those of primary human hepatocytes for several
      weeks at confluence. The present study was designed to evaluate their long-term
      functional stability and their response to repeated daily drug treatments over a
      14-day period, using a transcriptomic approach. Our data show that less than 1%
      of the expressed genes were markedly deregulated over this two weeks period and
      mainly included down-regulation of genes related to the cell cycle and from 3
      days, overexpression of genes involved in xenobiotic and lipid metabolism. After
      daily treatment with the three PPAR agonists, fenofibrate, troglitazone and
      rosiglitazone qualitative and/or quantitative changes in gene profiling were
      observed depending on the compound and duration of treatment. The highest
      increase in the number of deregulated genes as a function of drug treatment was
      seen with rosiglitazone. The most up-regulated genes common across the three
      compounds were mainly related to lipid and xenobiotic metabolisms. All the data
      support the conclusion that human HepaRG cells have an exceptional functional
      stability at confluence and that they are suitable for investigations on chronic
      effects of drugs and other chemicals.

PMID- 25572480
TI  - Targeting CD4(+) T cells for the treatment of sarcoidosis: a promising strategy?
AB  - Sarcoidois is an inflammatory disease of unknown origin characterized by the
      abnormal accumulation of noncaseating granulomas at sites of disease activity in
      multiple organs throughout the body with a predilection for the lungs. Because
      the exact trigger that leads to disease activity is still under investigation,
      current treatment options are contingent on the organ or organs affected.
      Corticosteroids are the therapy of choice, but antimalarials and TNF-alpha
      antagonists are also commonly prescribed. Recent findings provide evidence for
      the use of CD20 B-cell-depleting therapy as an alternative method of choice.
      However, because sarcoidosis is predominantly a T-helper cell-driven disorder, an
      overwhelming amount of compelling evidence exists for the use of CD4(+) T-cell
      targeted therapy. 

PMID- 25572482
TI  - Augmentative repetitive Transcranial Magnetic Stimulation (rTMS) in the acute
      treatment of poor responder depressed patients: a comparison study between high
      and low frequency stimulation.
AB  - BACKGROUND: While the efficacy of repetitive transcranial magnetic stimulation
      (rTMS) in Major Depressive Disorder (MDD) is well established, the debate is
      still open in relation to bipolar depression and to a possible different
      effectiveness of high vs. low stimulation. The present study was aimed to assess
      and compare the efficacy and tolerability of different protocols of augmentative
      rTMS in a sample of patients with current Major Depressive Episode (MDE), poor
      drug response/treatment resistance and a diagnosis of MDD or bipolar disorder.
      METHODS: Thirty-three patients were recruited in a 4-week, blind-rater, rTMS
      trial and randomised to the following three groups of stimulation: (1) (n=10)
      right dorsolateral prefrontal cortex (DLPFC) 1 HZ, 110% of the motor threshold
      (MT), 420 stimuli/day; (2) (n=10) right DLPFC, 1Hz, 110% MT, 900 stimuli/day; (3)
      (n=13) left DLPFC, 10Hz, 80% MT, 750 stimuli/day. RESULTS: Twenty-nine patients
      completed the treatment, showing a significant reduction of primary outcome
      measures (HAM-D, MADRS and CGI-S total scores: t=8.1, P<0.001; t=8.6, P<0.001;
      t=4.6, P<0.001 respectively). No significant differences in terms of efficacy and
      tolerability were found between high vs. low frequency and between unipolar and
      bipolar patients. Side effects were reported by 21% of the sample. One of the 4
      dropouts was caused by a hypomanic switch. CONCLUSIONS: Augmentative rTMS
      appeared to be effective and well tolerated for the acute treatment of unipolar
      and bipolar depression with features of poor drug response/treatment resistance,
      showing a comparable effectiveness profile between protocols of high and low
      frequency stimulation.

PMID- 25572483
TI  - Excessive checking behavior during an image comparison task in schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia display significant working memory and
      executive deficits. In patients with obsessive-compulsive disorder (OCD), several
      studies suggest that working memory dysfunction may be one of the causes of
      compulsive checking behaviors. Hence, this study aimed at assessing whether
      patients with schizophrenia were impaired on an image comparison task used to
      measure checking behaviors, and whether the origin and profile of impairment on
      this task was different between schizophrenia and OCD. METHODS: Eye movement
      recordings were used to assess the checking behavior of 24 patients with
      schizophrenia and 24 control participants who had to decide whether two images
      were different or identical. The verbal and visuo-spatial components of
      participants' working memory were measured using the reading span and backward
      location span tests. RESULTS: Compared to controls, patients with schizophrenia
      had reduced working memory spans and showed excessive checking behavior when
      comparing the two images. However, the intensity of their checking behavior was
      not significantly related to their working memory deficits. CONCLUSIONS: Several
      recent studies demonstrated that the excessive checking behaviors displayed by
      patients with OCD were related to working memory dysfunction. The absence of a
      relationship between the excessive checking behavior of patients with
      schizophrenia and their working memory deficits suggests that checking behaviors
      do not have the same origin in the two disorders.

PMID- 25572485
TI  - Creating a Bridge of Understanding between Two Worlds: Community-Based
      Collaborative-Action Research with Sudanese Refugee Women.
AB  - OBJECTIVE: To explore the process of partnership between university researchers,
      students, and South Sudanese refugee women to address the health challenges
      associated with their resettlement transition to the United States. DESIGN AND
      SAMPLE: This qualitative study used a community-based collaborative action
      research (CBCAR) framework in the design, collection, and analysis of the
      qualitative data. Twenty refugee women participated in this study. INTERVENTION:
      Five health education seminars followed by an audio-recorded focus group were
      held over 9 months. A final focus group was held to confirm derived themes and
      develop an action plan. RESULTS: The partnership between the refugee women and
      researchers resulted in awareness of how power structures and differing
      expectations affected the process. The dialog in the focus groups provided an
      opportunity for refugee women to voice challenges to their health in
      resettlement. A pattern was recognized about how political and sociocultural
      events affected the process of CBCAR. Dialog and sharing differing worldviews and
      perspectives led to insights about ways to improve the health of the South
      Sudanese refugee community. CONCLUSIONS: CBCAR is a useful framework to address
      health concerns of a refugee community. Insights from this study provided a
      foundation for a future intervention research project with the refugee women.

PMID- 25572484
TI  - Relationship of high-density lipoprotein cholesterol with periprocedural
      myocardial injury following elective percutaneous coronary intervention in
      patients with low-density lipoprotein cholesterol below 70 mg/dL.
AB  - BACKGROUND: Recent data showed inconsistent association of high-density
      lipoprotein cholesterol (HDL-C) with cardiovascular risk in patients with
      different levels of low-density lipoprotein cholesterol (LDL-C) or intensive
      statin therapy. This study sought to determine the relationship of HDL-C with
      periprocedural myocardial injury following elective percutaneous coronary
      intervention (PCI) across a range of LDL-C levels, especially in patients with
      LDL-C <70 mg/dL. METHODS AND RESULTS: We enrolled 2529 consecutive patients with
      normal preprocedural cardiac troponin I (cTnI) who underwent elective PCI. The
      association between preprocedural HDL-C and periprocedural myocardial injury was
      evaluated across LDL-C levels, especially in patients with LDL-C <70 mg/dL. The
      HDL-C level was not predictive of periprocedural myocardial injury across the
      entire study cohort. However, among patients with LDL-C <70 mg/dL, a 1 mg/dL
      increase in HDL-C was associated with a 3% reduced risk for postprocedural cTnI
      above 1*upper limit of normal (ULN) (odds ratio: 0.97; 95% CI: 0.95 to 0.99;
      P=0.004), a 3% reduced risk for postprocedural cTnI above 3*ULN odds ratio: 0.97;
      95% CI: 0.95 to 0.99; P=0.022), and a 3% reduced risk for postprocedural cTnI
      above 5*ULN (odds ratio: 0.97; 95% CI: 0.95 to 0.99; P=0.017). The relation
      between plasma HDL-C level and risk of postprocedural cTnI elevation above 1*ULN,
      3*ULN, and 5*ULN was modified by LDL-C level (all P for interaction <0.05).
      CONCLUSIONS: Higher HDL-C levels were associated with reduced risk of
      periprocedural myocardial injury only in patients with LDL-C <70 mg/dL.

PMID- 25572486
TI  - Remission of nephrotic syndrome due to AA-amyloidosis, complicating familiar
      Mediterranean fever, with tocilizumab.

PMID- 25572487
TI  - Brain MR image denoising for Rician noise using pre-smooth non-local means
      filter.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is corrupted by Rician noise, which
      is image dependent and computed from both real and imaginary images. Rician noise
      makes image-based quantitative measurement difficult. The non-local means (NLM)
      filter has been proven to be effective against additive noise. METHODS:
      Considering the characteristics of both Rician noise and the NLM filter, this
      study proposes a frame for a pre-smoothing NLM (PSNLM) filter combined with image
      transformation. In the PSNLM frame, noisy MRI is first transformed into an image
      in which noise can be treated as additive noise. Second, the transformed MRI is
      pre-smoothed via a traditional denoising method. Third, the NLM filter is applied
      to the transformed MRI, with weights that are computed from the pre-smoothed
      image. Finally, inverse transformation is performed on the denoised MRI to obtain
      the denoising results. RESULTS: To test the performance of the proposed method,
      both simulated and real patient data are used, and various pre-smoothing
      (Gaussian, median, and anisotropic filters) and image transformation [squared
      magnitude of the MRI, and forward and inverse variance-stabilizing trans
      formations (VST)] methods are used to reduce noise. The performance of the
      proposed method is evaluated through visual inspection and quantitative
      comparison of the peak signal-to-noise ratio of the simulated data. The real data
      include Alzheimer's disease patients and normal controls. For the real patient
      data, the performance of the proposed method is evaluated by detecting atrophy
      regions in the hippocampus and the parahippocampal gyrus. CONCLUSIONS: The
      comparison of the experimental results demonstrates that using a Gaussian pre
      smoothing filter and VST produce the best results for the peak signal-to-noise
      ratio (PSNR) and atrophy detection.

PMID- 25572488
TI  - Expression and function of fatty acid-binding protein 4 in epithelial cell of
      uterine endometrium.
AB  - The aims of this study were to delineate the expression of fatty-acid binding
      protein (FABP) 4 in human uterine endometrium and its function in the regulation
      of proliferation, migration and invasion of epithelial cells.
      Immunohistochenistry, immunofluorence and Western blotting were used to determine
      the expression and cellular localization of FABP4 in endometrium and endometrial
      epithelial cell lines. Interference of small ribonuclear acid (siRNA) and
      specific FABP4 inhibitor were used to inhibit FABP4. The proliferation, migration
      and invasion of epithelial cells were evaluated with CCK-8 assay, wound-healing
      test and transwell analysis respectively. We found that FABP4 was expressed by
      epithelial cells of proliferative endometrium and epithelial and stromal cells of
      secrectory endometrium. Epithelial cell lines Ishikawa and RL-952 expressed FABP4
      and this expression was decreased by FABP4 siRNA. FABP4 siRNA and specific FABP4
      inhibition significantly decreased the proliferation, migration and invasion of
      epithelial cell lines. We concluded that FABP4 is functionally expressed in
      endometrial epithelium and is necessary for maintaining the cell function of
      epithelial cells of endometrium. 

PMID- 25572489
TI  - Association between the nicotinamide adenine dinucleotide phosphate oxidase
      p22phox gene -A930G polymorphism and intracerebral hemorrhage.
AB  - The present study aimed to evaluate whether the -A930G polymorphism of the
      nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase p22phox gene is
      involved in intracerebral hemorrhage (ICH) in the Chinese Han population. In the
      present case-control investigation, the subjects included 118 patients with ICH
      and 147 healthy controls. The -A930G polymorphism was determined using polymerase
      chain reaction and restriction fragment length polymorphism. Furthermore, the
      correlation between the -A930G gene polymorphism and ICH was evaluated using
      statistical analyses. The distribution of p22phox -A930G genotypes differed
      significantly between the two groups (P=0.003), with the AA, AG and GG genotype
      frequencies being 61.9, 29.3 and 8.8% in the control group and 40.7, 45.8 and
      13.6% in the ICH group, respectively. The G allele frequency was significantly
      higher in patients with ICH compared with healthy controls (36.4 vs. 23.5%;
      P<0.05), however, the opposite was observed in the frequency of the A allele
      (63.6 vs. 76.5%; P<0.05). Binary logistic regression analysis revealed that
      genetic mutations of the p22phox -A930G gene were independent risk factors of ICH
      (odds ratio, 2.196; 95% confidence interval, 1.003-4.586; P=0.009). In addition,
      certain conventional factors were associated with increased risk of ICH,
      including elevated blood pressure, increased levels of glucose and triglycerides
      in the blood, a history of hypertension and smoking. The -A930G polymorphism of
      the p22phox gene may affect the susceptibility to ICH and certain haplotypes of
      the gene may be associated with a higher susceptibility to ICH.

PMID- 25572490
TI  - Eyelid lifting for ectropion and scleral show in facial palsy disease.
AB  - OBJECTIVE: To reduce eye disease, a simple surgical technique for the treatment
      of ectropion and scleral show was performed in patients affected by monolateral
      facial palsy. METHODS: Fifteen patients affected by facial palsy, degrees IV-VI
      according to the House-Brackmann grading scale, were evaluated with our surgical
      procedure, and the results were compared with several other procedures. RESULTS:
      We used an eye protection technique. Based on this, the dissection of the
      orbicular muscle was the more important procedure. It was possible to correct the
      ectropion and the lateral scleral show with only medial or lateral muscle flap
      sutures. A detailed description of the surgical procedures with a photographic
      history and instructions is given. CONCLUSION: Noninvasive surgery yielded good
      clinical results in 100% of the cases without any risk or subsequent
      reoccurrence.

PMID- 25572491
TI  - Positron emission tomography-adapted therapy for first-line treatment in
      individuals with Hodgkin lymphoma.
AB  - BACKGROUND: Hodgkin lymphoma (HL) is a B-cell lymphoma accounting for 10% to 15%
      of all lymphoma in industrialised countries. It has a bimodal age distribution
      with one peak around the age of 30 years and another after the age of 60 years.
      Although HL accounts for fewer than 1% of all neoplasms worldwide, it is
      considered to be one of the most common malignancies in young adults and, with
      cure rates of 90%, one of the most curable cancers worldwide. Current treatment
      options for HL comprise more- or less-intensified regimens of chemotherapy plus
      radiotherapy, depending on disease stage. [18F]-fluorodeoxy-D-glucose (FDG)
      positron emission tomography (PET, also called PET scanning) is an imaging tool
      that can be used to illustrate a tumour's metabolic activity, stage and
      progression. Therefore, it could be used as a standard interim procedure during
      HL treatment, to help distinguish between individuals who are good or poor early
      responders to therapy. Subsequent therapy could then be de-escalated in PET
      negative individuals (good responders) or escalated in those who are PET-positive
      (poor responders). It is currently unknown whether such response-adapted
      therapeutic strategies are of benefit to individuals in terms of overall and
      progression-free survival, and the incidence of long-term adverse events (AEs).
      OBJECTIVES: To assess the effects of interim [18F]-FDG-PET imaging treatment
      modification in individuals with HL. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL; latest issue) and MEDLINE (from
      1990 to September 2014) as well as conference proceedings (American Society of
      Hematology; American Society of Clinical Oncology; European Hematology
      Association; and International Symposium on Hodgkin Lymphoma) for studies. Two
      review authors independently screened search results. SELECTION CRITERIA: We
      included randomised controlled trials (RCTs) comparing FDG-PET-adapted therapy
      with non-adapted treatment in individuals with previously untreated HL of all
      stages and ages. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted data and assessed the quality of trials. As none of the included
      studies provided HRs for OS, we described risk ratios (RRs) for this outcome and
      did not pool the data. As an effect measure we used hazard ratios (HRs) for
      progression-free survival (PFS). We described RRs for the dichotomous data on
      AEs. We also calculated 95% confidence intervals (CIs). MAIN RESULTS: Our search
      strategies led to 308 potentially relevant references. From these, we included
      three studies involving 1999 participants. We judged the overall potential risk
      of bias as moderate. The studies were reported as RCTs; blinding was not
      reported, but given the study design it is likely that there was no blinding. One
      study was published in abstract form only; hence, detailed assessment of the risk
      of bias was not possible.Two trials compared standard treatment (chemotherapy
      plus radiotherapy) with PET-adapted therapy (chemotherapy only) in individuals
      with early-stage HL and negative PET scans. The study design of the third trial
      was more complex. Participants with early-stage HL were divided into those with a
      favourable or unfavourable prognosis. They were then randomised to receive PET
      adapted or standard treatment. Following a PET scan, participants were further
      divided into PET-positive and PET-negative groups. To date, data have been
      published for the PET-negative arms only, making it possible to perform a meta
      analysis including all three trials.Of the 1999 participants included in the
      three trials only 1480 were analysed. The 519 excluded participants were either
      PET-positive, or were excluded because they did not match the inclusion
      criteria.One study reported no deaths. The other two studies reported two deaths
      in participants receiving PET-adapted therapy and two in participants receiving
      standard therapy (very-low-quality evidence). Progression-free survival was
      shorter in participants with PET-adapted therapy (without radiotherapy) than in
      those receiving standard treatment with radiotherapy (HR 2.38; 95% CI 1.62 to
      3.50; P value < 0.0001). This difference was also apparent in comparisons of
      participants receiving no additional radiotherapy (PET-adapted therapy) versus
      radiotherapy (standard therapy) (HR 1.86; 95% CI 1.07 to 3.23; P value = 0.03)
      and in those receiving chemotherapy but no radiotherapy (PET-adapted therapy)
      versus standard radiotherapy (HR 3.00; 95% CI 1.75 to 5.14; P value < 0.0001)
      (moderate-quality evidence). Short-term AEs only were assessed in one trial,
      which showed no evidence of a difference between the treatment arms (RR 0.91; 95%
      CI 0.54 to 1.53; P value = 0.72) (very-low-quality evidence). No data on long
      term AEs were reported in any of the trials. AUTHORS' CONCLUSIONS: To date, no
      robust data on OS, response rate, TRM, QoL, or short- and long-term AEs are
      available. However, this systematic review found moderate-quality evidence that
      PFS was shorter in individuals with early-stage HL and a negative PET scan
      receiving chemotherapy only (PET-adapted therapy) than in those receiving
      additional radiotherapy (standard therapy). More RCTs with longer follow ups may
      lead to more precise results for AEs, TRM and QoL, and could evaluate whether
      this PFS advantage will translate into an overall survival benefit.It is still
      uncertain whether PET-positive individuals benefit from PET-based treatment
      adaptation and the effect of such an approach in those with advanced HL.

PMID- 25572492
TI  - Hymenobacter terrae sp. nov., a bacterium isolated from soil.
AB  - A Gram-negative, UV tolerant bacterial strain, DG7A(T), was isolated from soil
      samples collected in Seoul city, South Korea. The cells were grown on R2A agar at
      25  degrees C and were pink to red in color. The DNA G+C content of the novel
      strain DG7A was 63.5 mol%. Chemotaxonomic data revealed that the strains contain
      the major fatty acids iso-C15:0, anteiso-C15:0, and summed feature 3 (16:1
      omega7c/16:1 omega6c), with phosphatidylethanolamine as the major polar lipid.
      Phylogenetic analysis of the 16S rRNA gene sequences showed that strain DG7A(T)
      formed a distinct phylogenetic line along with Hymenobacter soli PB17(T), and
      they shared approximately 98.35 % 16S rRNA gene sequence similarity. However,
      these two strains shared only 5.3 % pairwise similarity (reciprocal analysis,
      36.3 %) in their genomic DNA. The next highest degree of 16S rRNA gene sequence
      similarity after H. soli PB17(T) was found with H. glaciei VUG-A130(T) (96.78 %),
      H. antarcticus VUG-A42aa(T) (96.66 %), and H. saemangeumensis GSR0100(T) (96.57
      %). Based on the phylogenetic analysis and analysis of the physiological and
      biochemical characteristics, this isolate was considered to represent a novel
      species, for which we propose the name Hymenobacter terrae sp. nov., with type
      strain DG7A(T) (= KCTC 32554(T) = KEMB 9004-164(T )= JCM 30007(T)).

PMID- 25572493
TI  - Sec pathway influences the growth of Deinococcus radiodurans.
AB  - The release of extracellular DNA molecules (eDNA) contributes to various
      biological processes, such as biofilm formation, virulence, and stress tolerance.
      The quantity of eDNA released by bacteria is usually regulated by extracellular
      nucleases that are secreted by different systems. In this study, we show that
      high concentrations of eDNA inhibit the growth of two strains of Deinococcaceae,
      Deinococcus radiodurans, and Deinococcus radiopugnans, but have no effect on
      other selected organisms, such as Escherichia coli. In D. radiodurans, an
      extracellular nuclease was shown to be secreted through the Sec pathway.
      Disruption of one member of this pathway, SecD/F, inhibited cell growth,
      suggesting that the Sec pathway plays an important role in growth rate. However,
      the Sec pathway mutant exhibited a greater deficiency in growth rate compared
      with the extracellular nuclease mutant, indicating that the pathway not only
      secretes the extracellular nuclease, but has other unknown functions as well.

PMID- 25572494
TI  - Plastorhodobacter daqingensis gen. nov., sp. nov.: a non-phototrophic bacterium
      isolated from Daqing Oilfield.
AB  - Two aerobic Gram staining negative, non-motile, and rod-shaped strains, DQW12E81
      30(T) and DQW12E6-37-1, were isolated from an oil production mixture from Daqing
      Oilfield, northeastern China. Phylogenetic analysis based on the nearly complete
      16S rRNA gene sequences revealed that strains DQW12E81-30(T) and DQW12E6-37-1
      were members of family Rhodobacteraceae, which showed 95.6-95.9 % of 16S rRNA
      gene sequence similarities with Pararhodobacter aggregans DSM 18938(T),
      Rhodobacter veldkampii CGMCC 1.5006(T), and Roseinatronobacter thiooxidans DSM
      13087(T), and lower similarities (<95.1 %) with all the left type species. Growth
      of strains DQW12E81-30(T) and DQW12E6-37-1 occurred at pH 7-8, 15-45  degrees C,
      and 0-4 % (w/v) of NaCl. The strains could grow both in dark and in light, but
      neither photosynthetic pigments nor photosynthetic reaction center gene pufM were
      detected in the strains. These photosynthesis-related features of the two
      isolates were different from those of Rhodobacter and Roseinatronobacter
      bacteria, but similar with those of Pararhodobacter. The genomic DNA G+C contents
      of strains DQW12E81-30(T) and DQW12E6-37-1 were 66.9 and 63.7 mol%, respectively.
      The predominant ubiquinone was Q-10 for both the strains. The major polar lipids
      of strain DQW12E81-30(T) were phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylcholine, unidentified aminolipid,
      unidentified glycolipid, and unidentified phospholipid. The two strains had C18:1
      omega7c, C18:0, and C18:1 omega7c 11-methyl as the major fatty acids. In
      addition, the strains DQW12E81-30(T) and DQW12E6-37-1 had C16:1 omega7c/C16:1
      omega6c, C12:0, C14:0, C14:0 3-OH/C16:1 iso I, C10:0 3-OH, which were remarkably
      different from those of Pararhodobacter and Roseinatronobacter. The results of
      phenotypic, genotypic, and chemotaxonomic characteristics analyses indicated that
      strains DQW12E81-30(T) and DQW12E6-37-1 were readily different from their most
      phylogenetically closely related genera. Plastorhodobacter daqingensis gen. nov,
      sp. nov. is proposed for strains DQW12E81-30(T) and DQW12E6-37-1. The type strain
      is DQW12E81-30(T) (=LMG 27732(T)=CGMCC 1.12750(T)).

PMID- 25572496
TI  - The yeast BDF1 regulates endocytosis via LSP1 under salt stress.
AB  - Bromodomain-containing transcription factor, a kind of important regulating
      protein, can recognize and bind to acetylated histone. The homologous genes, BDF1
      and BDF2, in Saccharomyces cerevisiae, respectively, encode a bromodomain
      containing transcription factor. Previously study has demonstrated that both BDF1
      and BDF2 participate in yeast salt stress response. Bdf1p deletion cells are
      sensitive to salt stress and this phenotype is suppressed by its homologue BDF2
      in a dosage-dependent manner. In this study, we show that the histone deacetylase
      SIR2 over-expression enhanced dosage-dependent compensation of BDF2. SIR2 over
      expression induced a global transcription change, and 1959 gene was down
      regulated. We deleted some of the most significant down-regulated genes and did
      the spot assay. The results revealed that LSP1, an upstream component of
      endocytosis pathway, and CIN5, a transcription factor that mediates cellular
      resistance to stresses, can enhance salt resistance of bdf1?. Further analysis
      demonstrated that under salt stress the endocytosis is over-activated in bdf1?
      but was recovered in bdf1? lsp1?. To our best knowledge, this is the first report
      that the transcription factor Bdf1p regulates endocytosis under salt stress via
      LSP1, a major component of eisosomes that regulate the sites of endocytosis.

PMID- 25572495
TI  - Relationship between adhesin genes and biofilm formation in vancomycin
      intermediate Staphylococcus aureus clinical isolates.
AB  - The adherence ability and biofilm production are the characteristic of enhanced
      virulence among isolates of vancomycin-intermediate Staphylococcus aureus (VISA)
      strains. Although biofilm-forming properties have been well demonstrated in S.
      aureus, they still remain unclear among the recently emerged types of VISA
      strains. The aim of this study was to investigate correlations between the
      distribution of genes encoding staphylococcal microbial surface components which
      recognise adhesive matrix molecules (MSCRAMMs), the surface protein A (Spa)
      types, MLST types and the ability of VISA strains to biofilm formation.
      Microtiter plate assay (Mtp) results showed that all eleven biofilm producer
      isolates were adherent at various levels. PCR experiments showed that nine
      MSCRAMM genes, clfA, clfB, fnbA and fib were detected in all of the strains,
      indicating a high prevalence. The prevalences of other MSCRAMMs and icaABCD genes
      were found to be variable and not equally distributed among the VISA strains.
      There was no direct correlation between the distribution of adhesion-related
      genes and biofilm formation, which indicates that the presence or absence of
      these genes cannot be employed as an indicator of the ability to biofilm
      formation. Isolates which belong to the same Spa and ST types showed similar
      adherence capacities in the Mtp assay, but significant differences were observed
      between different Spa types. The findings of this study, using quantitative
      methods, have shown that genotypically different strains of VISA have different
      capabilities to produce biofilms. This may be caused by a difference in the spa
      types of VISA isolates or due to their differences in the expression of MSCRAMM
      and icaABCD genes.

PMID- 25572497
TI  - Comparison of the noradrenergic sympathetic nerve contribution during local skin
      heating at forearm and leg sites in humans.
AB  - PURPOSE: We investigated the role of noradrenergic sympathetic nerves in the
      cutaneous circulation at rest and in response to local heating. METHODS: Dorsal
      forearm and lateral leg sites were each instrumented with 2 microdialysis fibers,
      2 local skin heaters, and 2 laser-Doppler probes. All sites were heated from 33
      degrees  to 42  degrees C. Each limb had 1 skin site treated with bretylium
      tosylate (BT) to block noradrenergic sympathetic neurotransmitter release and 1
      site infused with lactated Ringer's (Control). RESULTS: During baseline (33 
      degrees C), cutaneous vascular conductance (CVC; laser-Doppler flux/blood
      pressure) at control (24 +/- 2 %max) and BT-treated (29 +/- 4 %max) sites in the
      leg was significantly higher than the forearm (control: 12 +/- 1 %max; BT
      treated: 17 +/- 2 %max) (P = 0.032 and P = 0.042). At 42  degrees C local skin
      temperature, the initial peak CVC response with BT decreased compared to control
      at both forearm (62 +/- 3 vs. 86 +/- 6 %max, P < 0.01) and leg (67 +/- 3 vs. 77
      +/- 2 %max, P = 0.035) sites. CVC at the forearm with BT was lower than that of
      the leg (P = 0.02). With control, plateau phase (~35 min at 42  degrees C) CVC
      was greater in the leg (98 +/- 2 %max) than the forearm (89 +/- 4 %max) (P =
      0.027). BT reduced the peak CVC in the leg (90 +/- 4 %max, P = 0.027) and in the
      forearm (69 +/- 5 %max, P < 0.01). CVC at the BT-treated sites was reduced more
      in the forearm than in the legs (P < 0.01). CONCLUSIONS: The contribution of
      noradrenergic sympathetic nerves during local heating differs between leg and
      forearm at rest and with skin heating.

PMID- 25572499
TI  - Prognostic factors for early mortality in Parkinson's disease.
AB  - INTRODUCTION: There are few large studies that have evaluated prognostic factors
      for mortality in Parkinson's disease (PD). This large study aimed to identify
      demographic and clinical features associated with early mortality in PD. METHODS:
      PD patients at the National Neuroscience Institute were identified from the
      Movement Disorders Database from which demographic information and prospectively
      collected baseline disease characteristics were obtained. All study patients were
      linked to the Singapore Registry of Birth and Death to obtain information on
      vital status through December 31, 2012. The prognostic variables analyzed include
      patient demographics, baseline disease characteristics, and type of PD medication
      used. Multivariate Cox regression analysis was carried out to identify factors
      associated with the risk of mortality in PD. RESULTS: Of the 1786 PD patients
      identified, 363 (20.3%) had died during the 11-year study period. Median survival
      time from diagnosis was 15.8 years (range 0.3-31). Factors associated with higher
      mortality (HR, 95% CI) were older age at diagnosis (1.06, 1.03-1.08), male gender
      (2.29, 1.57-3.35), Hoehn & Yahr (HY) stage >= 2.5 (1.54, 1.07-2.22), UPDRS motor
      score >= 30 (1.63, 1.13-2.35), higher bradykinesia subscores (1.05, 1.01-1.09)
      and cognitive impairment (2.30, 1.55-3.41). CONCLUSIONS: In the largest study to
      date evaluating baseline disease characteristics prognostic of mortality risk in
      PD, we found that male gender, older age at diagnosis, higher baseline HY stage,
      higher baseline UPDRS motor scores, higher bradykinesia subscores and baseline
      cognitive impairment were associated with early mortality in PD.

PMID- 25572498
TI  - The relationship between real world ambulatory activity and falls in incident
      Parkinson's disease: influence of classification scheme.
AB  - INTRODUCTION: Few studies have categorized falls in early Parkinson's disease
      (PD) and little is known about falls incidence and evolution. Fall incidence and
      frequency are reported to be 'U' shaped with respect to disease severity and may
      be influenced by time spent engaged in ambulatory activity. METHODS: Twelve
      months prospective falls in an incident PD cohort (n = 111) were reported and the
      relationship between falls and ambulatory activity was examined in a subgroup (n
      = 83). Fall events were collected using standardised protocols and were
      categorized by fall frequency (non-faller, single fall, recurrent falls) and also
      by a novel classification based on pre-fall event: (1) engaged in advanced
      activity; (2) ambulation; and (3) transition. Non-parametric statistics compared
      groups in both classifications. RESULTS: At baseline 23 (20.7%) of the cohort had
      fallen, increasing to 41 (36.9%) participants over 12 months. Total time spent
      walking was significantly lower for transition fallers compared with non-fallers
      and ambulation fallers (p = 0.041), who also had significantly increased disease
      severity. There were no significant relationships when fallers were categorized
      by frequency. We present an inverted U curve model depicting the relationship
      between falls and activity over time in PD, and propose that at this stage
      transition and ambulation fallers occupy different places on the curve.
      CONCLUSIONS: Falls are more common than recognised in newly-diagnosed PD. Daily
      activity is reduced even in early disease for people who fall during transitions.
      Classification methods that take pre-fall event into account may be useful to
      understand the heterogeneity of this complex problem.

PMID- 25572500
TI  - Update on Huntington's disease: advances in care and emerging therapeutic
      options.
AB  - INTRODUCTION: Huntington's disease (HD) is the most common hereditary
      neurodegenerative disorder. Despite the fact that both the gene and the mutation
      causing this monogenetic disorder were identified more than 20 years ago, disease
      modifying therapies for HD have not yet been established. REVIEW: While intense
      preclinical research and large cohort studies in HD have laid foundations for
      tangible improvements in understanding HD and caring for HD patients, identifying
      targets for therapeutic interventions and developing novel therapeutic modalities
      (new chemical entities and advanced therapies using DNA and RNA molecules as
      therapeutic agents) continues to be an ongoing process. The authors review recent
      achievements in HD research and focus on approaches towards disease-modifying
      therapies, ranging from huntingtin-lowering strategies to improving huntingtin
      clearance that may be promoted by posttranslational HTT modifications.
      CONCLUSION: The nature and number of upcoming clinical studies/trials in HD is a
      reason for hope for HD patients and their families.

PMID- 25572502
TI  - Corrigendum.

PMID- 25572501
TI  - Role of manganese in protection against oxidative stress under iron starvation in
      cyanobacterium Anabaena 7120.
AB  - The cyanobacterium Anabaena sp. PCC 7120 was grown in presence and absence of
      iron to decipher the role of manganese in protection against the oxidative stress
      under iron starvation and growth, manganese uptake kinetics, antioxidative
      enzymes, lipid peroxidation, electrolyte leakage, thiol content, total peroxide,
      proline and NADH content was investigated. Manganese supported the growth of
      cyanobacterium Anabaena 7120 under iron deprived conditions where maximum uptake
      rate of manganese was observed with lower K(m) and higher V(max) values.
      Antioxidative enzymes were also found to be elevated in iron-starved conditions.
      Estimation of lipid peroxidation and electrolyte leakage depicted the role of
      manganese in stabilizing the integrity of the membrane which was considered as
      the prime target of oxygen free radicals in oxidative stress. The levels of total
      peroxide, thiol, proline and NADH content, which are the representative of
      oxidative stress response in Anabaena 7120, were also showed increasing trends in
      iron starvation. Hence, the results discerned, clearly suggested the role of
      manganese in protection against the oxidative stress in cyanobacterium Anabaena
      7120 under iron starvation either due to its antioxidative properties or
      involvement as cofactor in a number of antioxidative enzymes.

PMID- 25572503
TI  - Cost-effectiveness of revascularization strategies: the ASCERT study.
AB  - BACKGROUND: ASCERT (American College of Cardiology Foundation and the Society of
      Thoracic Surgeons Collaboration on the Comparative Effectiveness of
      Revascularization Strategies) was a large observational study designed to compare
      the long-term effectiveness of coronary artery bypass graft (CABG) and
      percutaneous coronary intervention (PCI) to treat coronary artery disease (CAD)
      over 4 to 5 years. OBJECTIVES: This study examined the cost-effectiveness of CABG
      versus PCI for stable ischemic heart disease. METHODS: The Society of Thoracic
      Surgeons and American College of Cardiology Foundation databases were linked to
      the Centers for Medicare and Medicaid Services claims data. Costs for the index
      and observation period (2004 to 2008) hospitalizations were assessed by diagnosis
      related group Medicare reimbursement rates; costs beyond the observation period
      were estimated from average Medicare participant per capita expenditure.
      Effectiveness was measured via mortality and life-expectancy data. Cost and
      effectiveness comparisons were adjusted using propensity score matching with the
      incremental cost-effectiveness ratio expressed as cost per quality-adjusted life
      year gained. RESULTS: CABG patients (n = 86,244) and PCI patients (n = 103,549)
      were at least 65 years old with 2- or 3-vessel coronary artery disease. Adjusted
      costs were higher for CABG for the index hospitalization, study period, and
      lifetime by $10,670, $8,145, and $11,575, respectively. Patients undergoing CABG
      gained an adjusted average of 0.2525 and 0.3801 life-years relative to PCI over
      the observation period and lifetime, respectively. The life-time incremental cost
      effectiveness ratio of CABG compared to PCI was $30,454/QALY gained. CONCLUSIONS:
      Over a period of 4 years or longer, patients undergoing CABG had better outcomes
      but at higher costs than those undergoing PCI.

PMID- 25572504
TI  - ASCERTing the value of coronary artery bypass graft in stable angina patients:
      the challenges and potential of observational research to improve care.

PMID- 25572506
TI  - Infections following cardiac surgery: an opportunity for clarity.

PMID- 25572505
TI  - Costs associated with health care-associated infections in cardiac surgery.
AB  - BACKGROUND: Health care-associated infections (HAIs) are the most common
      noncardiac complications after cardiac surgery and are associated with increased
      morbidity and mortality. Current information about their economic burden is
      limited. OBJECTIVES: This research was designed to determine the cost associated
      with major types of HAIs during the first 2 months after cardiac surgery.
      METHODS: Prospectively collected data from a multicenter, observational study of
      the Cardiothoracic Surgery Clinical Trials Network, in which patients were
      monitored for infections for 65 days after surgery, were merged with related
      financial data routinely collected by the University HealthSystem Consortium.
      Incremental length of stay (LOS) and cost associated with HAIs were estimated
      using generalized linear models, with adjustments for patient demographics,
      clinical history, baseline laboratory values, and surgery type. RESULTS: Among
      4,320 cardiac surgery patients (mean age: 64 +/- 13 years), 119 (2.8%)
      experienced a major HAI during the index hospitalization. The most common HAIs
      were pneumonia (48%), sepsis (20%), and Clostridium difficile colitis (18%). On
      average, the estimated incremental cost associated with a major HAI was nearly
      $38,000, of which 47% was related to intensive care unit services. The
      incremental LOS was 14 days. Overall, there were 849 readmissions; among these,
      8.7% were attributed to major HAIs. The cost of readmissions due to major HAIs
      was, on average, nearly threefold that of readmissions not related to HAIs.
      CONCLUSIONS: Hospital cost, LOS, and readmissions are strongly associated with
      HAIs. These associations suggest the potential for large reductions in costs if
      HAIs following cardiac surgery can be reduced. (Management Practices and the Risk
      of Infections Following Cardiac Surgery; NCT01089712).

PMID- 25572507
TI  - Bivalirudin versus heparin with or without glycoprotein IIb/IIIa inhibitors in
      patients with STEMI undergoing primary percutaneous coronary intervention: pooled
      patient-level analysis from the HORIZONS-AMI and EUROMAX trials.
AB  - BACKGROUND: In the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and
      Stents in Acute Myocardial Infarction) trial, 3,602 patients undergoing primary
      percutaneous coronary intervention (PCI) for ST-segment elevation myocardial
      infarction (STEMI) treated with bivalirudin had lower bleeding and mortality
      rates, but higher acute stent thrombosis rates compared with heparin + a
      glycoprotein IIb/IIIa inhibitor (GPI). Subsequent changes in primary PCI,
      including the use of potent P2Y12 inhibitors, frequent radial intervention, and
      pre-hospital medication administration, were incorporated into the EUROMAX
      (European Ambulance Acute Coronary Syndrome Angiography) trial, which assigned
      2,218 patients to bivalirudin versus heparin +/- GPI before primary PCI.
      OBJECTIVES: The goal of this study was to examine the outcomes of procedural
      anticoagulation with bivalirudin versus heparin +/- GPI for primary PCI, given
      the evolution in primary PCI. METHODS: Databases from HORIZONS-AMI and EUROMAX
      were pooled for patient-level analysis. The Breslow-Day test evaluated
      heterogeneity between trials. RESULTS: A total of 5,800 patients were randomized
      to bivalirudin (n = 2,889) or heparin +/- GPI (n = 2,911). The radial approach
      was used in 21.3% of patients, prasugrel/ticagrelor was used in 18.1% of
      patients, and GPI was used in 84.8% of the control group. Bivalirudin compared
      with heparin +/- GPI resulted in reduced 30-day rates of major bleeding (4.2% vs.
      7.8%; relative risk [RR]: 0.53; 95% confidence interval [CI]: 0.43 to 0.66; p <
      0.0001), thrombocytopenia (1.4% vs. 2.9%, RR: 0.48; 95% CI: 0.33 to 0.71; p =
      0.0002), and cardiac mortality (2.0% vs. 2.9%; RR: 0.70; 95% CI: 0.50 to 0.97; p
      = 0.03), with nonsignificantly different rates of reinfarction, ischemia-driven
      revascularization, stroke, and all-cause mortality. Bivalirudin resulted in
      increased acute (<24 h) stent thrombosis rates (1.2% vs. 0.2%; RR: 6.04; 95% CI:
      2.55 to 14.31; p < 0.0001), with nonsignificantly different rates of subacute
      stent thrombosis. Composite net adverse clinical events were lower with
      bivalirudin (8.8% vs. 11.9%; RR: 0.74; 95% CI: 0.63 to 0.86; p < 0.0001). There
      was no significant heterogeneity between the 2 trials for these outcomes, and
      results were consistent across major subgroups. CONCLUSIONS: Despite increased
      acute stent thrombosis, primary PCI with bivalirudin improved 30-day net clinical
      outcomes, with significant reductions in major bleeding, thrombocytopenia, and
      transfusions compared with heparin +/- GPI, results that were consistent with
      evolution in PCI technique and pharmacotherapy. (Harmonizing Outcomes with
      RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI];
      NCT00433966) (European Ambulance Acute Coronary Syndrome Angiography [EUROMAX];
      NCT01087723).

PMID- 25572508
TI  - Choice of optimal anticoagulant to support primary PCI: out with the new, in with
      the old.

PMID- 25572510
TI  - Healthy habits, healthy women.

PMID- 25572509
TI  - Healthy lifestyle in the primordial prevention of cardiovascular disease among
      young women.
AB  - BACKGROUND: Overall mortality rates from coronary heart disease (CHD) in the
      United States have declined in recent decades, but the rate has plateaued among
      younger women. The potential for further reductions in mortality rates among
      young women through changes in lifestyle is unknown. OBJECTIVES: The aim of this
      study was to estimate the proportion of CHD cases and clinical cardiovascular
      disease (CVD) risk factors among young women that might be attributable to poor
      adherence to a healthy lifestyle. METHODS: A prospective analysis was conducted
      among 88,940 women ages 27 to 44 years at baseline in the Nurses' Health Study II
      who were followed from 1991 to 2011. Lifestyle factors were updated repeatedly by
      questionnaire. A healthy lifestyle was defined as not smoking, a normal body mass
      index, physical activity >= 2.5 h/week, television viewing <= 7 h/week, diet in
      the top 40% of the Alternative Healthy Eating Index-2010, and 0.1 to 14.9 g/day
      of alcohol. To estimate the proportion of CHD and clinical CVD risk factors
      (diabetes, hypertension, and hypercholesterolemia) that could be attributed to
      poor adherence to a healthy lifestyle, we calculated the population-attributable
      risk percent. RESULTS: During 20 years of follow-up, we documented 456 incident
      CHD cases. In multivariable-adjusted models, nonsmoking, a healthy body mass
      index, exercise, and a healthy diet were independently and significantly
      associated with lower CHD risk. Compared with women with no healthy lifestyle
      factors, the hazard ratio for CHD for women with 6 lifestyle factors was 0.08
      (95% confidence interval: 0.03 to 0.22). Approximately 73% (95% confidence
      interval: 39% to 89%) of CHD cases were attributable to poor adherence to a
      healthy lifestyle. Similarly, 46% (95% confidence interval: 43% to 49%) of
      clinical CVD risk factor cases were attributable to a poor lifestyle.
      CONCLUSIONS: Primordial prevention through maintenance of a healthy lifestyle
      among young women may substantially lower the burden of CVD.

PMID- 25572511
TI  - Low-gradient, low-flow severe aortic stenosis with preserved left ventricular
      ejection fraction: characteristics, outcome, and implications for surgery.
AB  - BACKGROUND: Severe low-gradient, low-flow (LG/LF) aortic stenosis with preserved
      left ventricular ejection fraction (EF) has been described as a more advanced
      form of aortic stenosis. However, the natural history and need for surgery in
      patients with LG/LF aortic stenosis remain subjects of intense debate.
      OBJECTIVES: We sought to investigate the outcome of LG/LF aortic stenosis in
      comparison with moderate aortic stenosis and with high-gradient (HG) aortic
      stenosis in a real-world study, in the context of routine practice. METHODS: This
      analysis included 809 patients (ages 75 +/- 12 years) diagnosed with aortic
      stenosis and preserved EF (>=50%). Patients were divided into 4 groups: mild-to
      moderate aortic stenosis; HG aortic stenosis; LG/LF aortic stenosis; and low
      gradient, normal-flow (LG/NF) aortic stenosis. RESULTS: Compared with mild-to
      moderate aortic stenosis patients, LG/LF aortic stenosis patients had smaller
      valve areas and stroke volumes, higher mean gradients, and comparable degrees of
      ventricular hypertrophy. Under medical management (22.8 months; range 7 to 53
      months), compared with mild-to-moderate aortic stenosis patients, HG aortic
      stenosis patients were at higher risk of death (adjusted hazard ratio [HR]: 1.47;
      95% confidence interval [CI]: 1.03 to 2.07), whereas LG/LF aortic stenosis
      patients did not have an excess mortality risk (adjusted HR: 0.88; 95% CI: 0.53
      to 1.48). During the entire (39.0 months; range 11 to 69 months) follow-up (with
      medical and surgical management), the mortality risk associated with LG/LF aortic
      stenosis was close to that of mild-to-moderate aortic stenosis (adjusted HR:
      0.96; 95% CI: 0.58 to 1.53), whereas the excess risk of death associated with HG
      aortic stenosis was confirmed (adjusted HR: 1.74; 95% CI: 1.27 to 2.39). The
      benefit associated with aortic valve replacement was confined to the HG aortic
      stenosis group (adjusted HR: 0.29; 95% CI: 0.18 to 0.46) and was not observed for
      LG/LF aortic stenosis (adjusted HR: 0.75; 95% CI: 0.14 to 4.05). CONCLUSIONS: In
      this study, the outcome of severe LG/LF aortic stenosis with preserved EF was
      similar to that of mild-to-moderate aortic stenosis and was not favorably
      influenced by aortic surgery. Further research is needed to better understand the
      natural history and the progression of LG/LF aortic stenosis.

PMID- 25572512
TI  - Management of paradoxical low-flow, low-gradient aortic stenosis: need for an
      integrated approach, including assessment of symptoms, hypertension, and stenosis
      severity.

PMID- 25572515
TI  - How to handle conflict with poise?: a fellow's perspective.

PMID- 25572514
TI  - Hybrid coronary revascularization: promising, but yet to take off.
AB  - Hybrid coronary revascularization (HCR) combines arterial coronary artery bypass
      surgery (most commonly minimally invasive) and percutaneous coronary intervention
      in the treatment of a particular subset of multivessel coronary artery disease.
      It was first introduced in the mid-1990s, and aspired to bring together the "best
      of both worlds": the excellent patency rates and survival benefits associated
      with the durable left internal mammary artery graft to the left anterior
      descending artery alongside the good patency rates of drug-eluting stents, which
      outlive saphenous vein grafts to non-left anterior descending vessels. Although
      in theory this is a very attractive revascularization strategy, several years
      later, only one small randomized controlled trial comparing HCR with coronary
      artery bypass grafting has recently emerged in the medical literature, raising
      concerns regarding HCR's role and generalizability. In the current review, we
      discuss HCR's rationale, the current evidence behind it, its limitations and
      procedural challenges.

PMID- 25572516
TI  - The natural course of healthy obesity over 20 years.

PMID- 25572517
TI  - Noncorticosteroid immunosuppression limits myocardial damage and contractile
      dysfunction in eosinophilic granulomatosis with polyangiitis (Churg-Strauss
      syndrome).

PMID- 25572518
TI  - Delegation of duties and professional standards.

PMID- 25572513
TI  - Mechanisms and clinical consequences of untreated central sleep apnea in heart
      failure.
AB  - Central sleep apnea (CSA) is a highly prevalent, though often unrecognized,
      comorbidity in patients with heart failure (HF). Data from HF population studies
      suggest that it may present in 30% to 50% of HF patients. CSA is recognized as an
      important contributor to the progression of HF and to HF-related morbidity and
      mortality. Over the past 2 decades, an expanding body of research has begun to
      shed light on the pathophysiologic mechanisms of CSA. Armed with this growing
      knowledge base, the sleep, respiratory, and cardiovascular research communities
      have been working to identify ways to treat CSA in HF with the ultimate goal of
      improving patient quality of life and clinical outcomes. In this paper, we
      examine the current state of knowledge about the mechanisms of CSA in HF and
      review emerging therapies for this disorder.

PMID- 25572519
TI  - Nurse practitioners (and other physician extenders) are not an appropriate
      replacement for expert physician electrocardiogram readers in routine clinical
      practice.

PMID- 25572520
TI  - Reply: nurse practitioners (and other physician extenders) are not an appropriate
      replacement for expert physician electrocardiogram readers in routine clinical
      practice.

PMID- 25572521
TI  - Statin-induced low low-density lipoprotein cholesterol level: is lower better?

PMID- 25572522
TI  - Reply: statin-induced low low-density lipoprotein cholesterol level: is lower
      better?

PMID- 25572523
TI  - Effect of prenatal exposure of lindane on alterations in the expression of
      cerebral cytochrome P450s and neurotransmitter receptors in brain regions.
AB  - Prenatal exposure to low doses (0.0625- or 0.125- or 0.25 mg/kg b. wt., orally)
      of lindane, an organochlorine insecticide, from gestation day (GD) 5-21 was found
      to produce a dose-dependent increase in the mRNA expression of cytochrome P450s
      (CYPs) and associated transcription factors in frontal cortex, cerebellum and
      corpus striatum isolated from the offsprings. Though the increase in the
      expression persisted up to postnatal day 60, the increase was significant at
      postnatal days 21-, and 45- in the offsprings exposed prenatally to relatively
      higher doses (0.125- or 0.25 mg/kg) of lindane and even up to postnatal day 60 in
      the offsprings exposed prenatally to the highest dose of lindane. A similar
      increase in the expression of dopamine D2, 5HT2A and GABAA receptors and
      associated neurotransmitter receptor binding was observed in the brain regions of
      the exposed offsprings. Scatchard analysis also suggested an increase in the
      levels of these neurotransmitter receptors in offsprings prenatally exposed to
      lindane. The data indicating similarities in the alterations of neurotransmitter
      receptors and CYPs in brain regions in prenatally exposed offsprings have
      suggested that neurotransmission processes and CYPs are closely linked that will
      eventually help in understanding the developmental neurotoxicity of lindane. 

PMID- 25572525
TI  - Jalpaite Ag3CuS2: a novel promising ternary sulfide absorber material for solar
      cells.
AB  - We report a novel promising semiconductor of Ag3CuS2 serving as absorber material
      in inorganic-organic solid-state solar cells for the first time, and the device
      (ITO/ZnO/Ag3CuS2/P3HT/Pt) exhibits a power conversion efficiency of 2.01%. This
      study opens up an available method to develop various ternary absorber materials
      for tertiary generation solar cells. 

PMID- 25572527
TI  - Layer-by-layer assembly of a redox enzyme displayed on the surface of elongated
      bacteria into a hierarchical artificial biofilm based anode.
AB  - To achieve an efficient electron transfer communication between bacteria and
      electrodes, several strategies including enzyme surface display, bacteria
      elongation as well as layer-by-layer assembly techniques were used to assemble
      bacteria, methylene blue, multiwall carbon nanotubes, and carbon papers into
      hierarchical micro/nano artificial biofilm based bioanodes. 

PMID- 25572526
TI  - Molecular analysis of faecal samples from birds to identify potential crop pests
      and useful biocontrol agents in natural areas.
AB  - Wild habitats adjoining farmland are potentially valuable sources of natural
      enemies, but also of pests. Here we tested the utility of birds as 'sampling
      devices', to identify the diversity of prey available to predators and
      particularly to screen for pests and natural enemies using natural ecosystems as
      refugia. Here we used PCR to amplify prey DNA from three sympatric songbirds
      foraging on small invertebrates in Phragmites reedbed ecosystems, namely the Reed
      Warbler (Acrocephalus scirpaceus), Sedge Warbler (Acrocephalus schoenobaenus) and
      Cetti's Warbler (Cettia cetti). A recently described general invertebrate primer
      pair was used for the first time to analyse diets. Amplicons were cloned and
      sequenced, then identified by reference to the Barcoding of Life Database and to
      our own sequences obtained from fresh invertebrates. Forty-five distinct prey DNA
      sequences were obtained from 11 faecal samples, of which 39 could be identified
      to species or genus. Targeting three warbler species ensured that species
      specific differences in prey choice broadened the range of prey taken. Amongst
      the prey found in reedbeds were major pests (including the tomato moth Lacanobia
      oleracea) as well as many potentially valuable natural enemies including
      aphidophagous hoverflies and braconid wasps. Given the mobility of birds, this
      approach provides a practical way of sampling a whole habitat at once, providing
      growers with information on possible invasion by locally resident pests and the
      colonization potential of natural enemies from local natural habitats. 

PMID- 25572524
TI  - Licochalcone-A induces intrinsic and extrinsic apoptosis via ERK1/2 and p38
      phosphorylation-mediated TRAIL expression in head and neck squamous carcinoma
      FaDu cells.
AB  - We investigated Licochalcone-A (Lico-A)-induced apoptosis and the pathway
      underlying its activity in a pharyngeal squamous carcinoma FaDu cell line. Lico-A
      purified from root of Glycyrrhiza inflata had cytotoxic effects, significantly
      increasing cell death in FaDu cells. Using a cell viability assay, we determined
      that the IC50 value of Lico-A in FaDu cells was approximately 100 uM. Chromatin
      condensation was observed in FaDu cells treated with Lico-A for 24 h. Consistent
      with this finding, the number of apoptotic cells increased in a time-dependent
      manner when FaDu cells were treated with Lico-A. TRAIL was significantly up
      regulated in Lico-A-treated FaDu cells in a dose-dependent manner. Apoptotic
      factors such as caspases and PARP were subsequently activated in a caspase
      dependent manner. In addition, levels of pro-apoptotic factors increased
      significantly in response to Lico-A treatment, while levels of anti-apoptotic
      factors decreased. Lico-A-induced TRAIL expression was mediated in part by a MAPK
      signaling pathway involving ERK1/2 and p38. In xenograft mouse model, Lico-A
      treatment effectively suppressed the growth of FaDu cell xenografts by activating
      caspase-3, without affecting the body weight of mice. Taken together, these data
      suggest that Lico-A has potential chemopreventive effects and should therefore be
      developed as a chemotherapeutic agent for pharyngeal squamous carcinoma. 

PMID- 25572528
TI  - Improved solid-phase DNA probe method for tRNA purification: large-scale
      preparation and alteration of DNA fixation.
AB  - The solid-phase DNA probe method, in which a target transfer RNA (tRNA) is
      hybridized with a complementary DNA oligomer, is generally used for tRNA
      purification. However, purification of tRNAs from thermophiles by this method is
      not easy because of their high melting temperatures. To overcome this problem,
      the use of tetraalkylammonium salts was previously reported [Yokogawa, T.,
      Kitamura, Y., Nakamura, D., Ohno, S., and Nishikawa, K. (2010) Optimization of
      the hybridization-based method for purification of thermostable tRNAs in the
      presence of tetraalkylammonium salts. Nucleic Acids Res. 38, e89]. In this study,
      we initially devised a large-scale purification system using tetraalkylammonium
      salts. The yield of tRNA was increased more than 10-fold and the manual steps
      were decreased as compared with the previous procedure. However, deterioration of
      column was very rapid owing to shedding of the biotinylated DNA probe. We
      therefore devised a method of covalent DNA fixation, in which a 5'-aminohexyl
      (dT)8 oligomer was fixed onto the N-hydroxysuccinimide-activated agarose, and
      then a DNA oligomer containing the tRNA and repeated A8 sequences was annealed.
      The probe sequence for tRNA purification was synthesized in column with Klenow
      enzyme. This DNA fixation method enabled us to use the column repeatedly and to
      wash the column with warmed buffers. Thus, this DNA fixation method is economical
      as compared with the previous method using the biotinylated DNA probe. 

PMID- 25572529
TI  - Icotinib hydrochloride enhances the effect of radiotherapy by affecting DNA
      repair in colorectal cancer cells.
AB  - The aim of the present study was to explore the efficacy and mechanism of the
      radiosensitisation of icotinib hydrochloride (IH), a novel oral epidermal growth
      factor receptor-tyrosine kinase activity inhibitor, by evaluating the changes in
      tumour cell double-strand breaks (DSBs) repair, cell cycle and apoptosis
      following a combination of IH and radiotherapy (RT) in human colorectal
      adenocarcinoma cell lines. The HT29 and HCT116 human CRC cell lines were treated
      with IH and/or radiation. Effects on cell viability and cell cycle progression
      were measured by MTT, a clonogenic survival assay, and flow cytometry.
      Immunofluorescent staining and western blot analysis were applied to detect the
      expression of gamma-H2AX and 53BP1 in the different treatment groups. Finally,
      the in vivo effect on the growth of CRC xenografts was assessed in athymic nude
      mice. IH inhibited the proliferation and enhanced the radiosensitivity in HT29
      and HCT116 CRC cells lines. IH combined with radiation increased cell cycle
      arrest in the G2/M phase compared to the other treatments in the HT29 cell line
      (P<0.05). Similarly, cell cycle arrest occurred in the HCT116 cell line, although
      this increase did not result in significant differences in the RT group (P>0.05).
      IH combined with radiation significantly inhibited the expression of gamma-H2AX
      and 53BP1 based on results of immunofluorescent staining and western blot
      analysis. In vivo, IH plus radiation significantly inhibited the tumour growth
      compared to either agent independently. In conclusion, IH significantly increased
      the radiosensitivity of HT29 and HCT116 cells in vitro and in vivo. Radiation
      combined with EGFR blockade inhibited tumour proliferation, increased apoptosis,
      prolonged G2/M arrest and significantly enhanced DNA injury in colorectal cancer.
      These data support the clinical trials of biologically targeted and conventional
      therapies in the treatment of cancer.

PMID- 25572530
TI  - Memory impairment and alterations in prefrontal cortex gamma band activity
      following methamphetamine sensitization.
AB  - RATIONALE: Repeated methamphetamine (MA) use leads to increases in the incentive
      motivational properties of the drug as well as cognitive impairments. These
      behavioral alterations persist for some time following abstinence, and
      neuroadaptations in the structure and function of the prefrontal cortex (PFC) are
      particularly important for their expression. However, there is a weak
      understanding of the changes in neural firing and oscillatory activity in the PFC
      evoked by repeated drug use, thus complicating the development of novel treatment
      strategies for addiction. OBJECTIVES: The purpose of the current study was to
      assess changes in cognitive and brain function following MA sensitization.
      METHODS: Sensitization was induced in rats, then temporal and recognition memory
      were assessed after 1 or 30 days of abstinence. Electrophysiological recordings
      from the medial PFC were also acquired from rats whereupon simultaneous measures
      of oscillatory and spiking activity were examined. RESULTS: Impaired temporal
      memory was observed after 1 and 30 days of abstinence. However, recognition
      memory was only impaired after 1 day of abstinence. An injection of MA profoundly
      decreased neuronal firing rate and the anesthesia-induced slow oscillation (SO)
      in both sensitized (SENS) and control (CTRL) rats. Strong correlations were
      observed between the SO and gamma band power, which was altered in SENS animals.
      A decrease in the number of neurons phase-locked to the gamma oscillation was
      also observed in SENS animals. CONCLUSIONS: The changes observed in PFC function
      may play an integral role in the expression of the altered behavioral phenotype
      evoked by MA sensitization.

PMID- 25572531
TI  - Psychostimulants and atomoxetine alter the electrophysiological activity of
      prefrontal cortex neurons, interaction with catecholamine and glutamate NMDA
      receptors.
AB  - RATIONALE: Attention-deficit hyperactivity disorder (ADHD) is the most frequently
      diagnosed neuropsychiatric disorder in childhood. Currently available ADHD drugs
      include the psychostimulants methylphenidate (MPH) and D-amphetamine (D-AMP),
      acting on norepinephrine and dopamine transporters/release, and atomoxetine
      (ATX), a selective norepinephrine uptake inhibitor. Recent evidence suggests an
      involvement of glutamate neurotransmission in the pathology and treatment of
      ADHD, via mechanisms to be clarified. OBJECTIVE: We have investigated how ADHD
      drugs could modulate, through interaction with catecholamine receptors, basal and
      glutamate-induced excitability of pyramidal neurons in the prefrontal cortex
      (PFC), a region which plays a major role in control of attention and impulsivity.
      METHODS: We have used the technique of extracellular single-unit recording in
      anaesthetised rats coupled with microiontophoresis. RESULTS: Both MPH (1-3 mg/kg)
      and D-AMP (1-9 mg/kg) increased the firing activity of PFC neurons in a dopamine
      D1 receptor-dependent manner. ATX administration (1-6 mg/kg) also increased the
      firing of neurons, but this effect is not significantly reversed by D1 (SCH
      23390) or alpha1 (prazosin) receptor antagonists but potentiated by alpha2
      antagonist (yohimbine). All drugs induced a clear potentiation of the excitatory
      response of PFC neurons to the microiontophoretic application of the glutamate
      agonist N-methyl-D-aspartate (NMDA), but not to the glutamate agonist alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). The potentiating effect of D
      AMP on NMDA-induced activation of PFC neurons was partially reversed or prevented
      by dopamine D1 receptor blockade. CONCLUSION: Our data shows that increase in
      excitability of PFC neurons in basal conditions and via NMDA receptor activation
      may be involved in the therapeutic response to ADHD drugs.

PMID- 25572533
TI  - Deficiency of both L-selectin and ICAM-1 exacerbates imiquimod-induced psoriasis
      like skin inflammation through increased infiltration of antigen presenting
      cells.
AB  - To assess the role of inter-cellular adhesion molecule (ICAM)-1 and L-selectin in
      psoriasis pathogenic process, we examined the psoriasiform skin inflammation
      triggered by imiquimod, a toll-like receptor 7/8 agonist, in mice lacking ICAM-1
      (ICAM-1(-/-)), L-selectin (L-selectin(-/-)), or both (L-selectin/ICAM-1(-/-)).
      Disease severity was significantly reduced in ICAM-1(-/-) and L-selectin(-/-)
      mice compared with wild type mice, while it was exacerbated in L-selectin/ICAM-1(
      /-) mice. Cutaneous interleukin (IL)-17A, IL-23, and tumor necrosis factor (TNF)
      alpha expression was increased in L-selectin/ICAM-1(-/-) mice compared with wild
      type mice. Furthermore, only L-selectin/ICAM-1(-/-) mice was refractory to anti
      TNF-alpha antibody treatment. The skin lesion from L-selectin/ICAM-1(-/-) mice
      showed augmented E-selectin expression compared with ICAM-1(-/-) and L-selectin(
      /-) mice, and augmented E-selectin ligand-1 expression compared with wild type
      mice. The current study demonstrates that although ICAM-1 and L-selectin regulate
      psoriasiform inflammation, deleting both L-selectin and ICAM-1 simultaneously
      would rather induce refractory skin inflammation, due to compensatory up
      regulation of other adhesion molecules. 

PMID- 25572534
TI  - Semi-automated and standardized cytometric procedures for multi-panel and multi
      parametric whole blood immunophenotyping.
AB  - Immunophenotyping by multi-parametric flow cytometry is the cornerstone
      technology for enumeration and characterization of immune cell populations in
      health and disease. Standardized procedures are essential to allow for inter
      individual comparisons in the context of population based or clinical studies.
      Herein we report the approach taken by the Milieu Interieur Consortium,
      highlighting the standardized and automated procedures used for immunophenotyping
      of human whole blood samples. We optimized eight-color antibody panels and
      procedures for staining and lysis of whole blood samples, and implemented pre
      analytic steps with a semi-automated workflow using a robotic system. We report
      on four panels that were designed to enumerate and phenotype major immune cell
      populations (PMN, T, B, NK cells, monocytes and DC). This work establishes a
      foundation for defining reference values in healthy donors. Our approach provides
      robust protocols for affordable, semi-automated eight-color cytometric
      immunophenotyping that can be used in population-based studies and clinical trial
      settings. 

PMID- 25572532
TI  - The osteopontin transgenic mouse is a new model for Sjogren's syndrome.
AB  - Osteopontin (Opn) is a cytokine involved in both physiological and pathological
      processes, and is elevated in many autoimmune diseases. Sjogren's syndrome (SS)
      is an autoimmune disease with a strong female predilection characterized by
      lymphocytic infiltration of exocrine glands. We hypothesized that Opn contributes
      to SS pathogenesis. We examined an established SS model and found increased Opn
      locally and systemically. Next, we examined Opn transgenic (Opn Tg) mice for
      evidence of SS. Opn Tg animals exhibited lymphocytic infiltration of salivary and
      lacrimal glands, and Opn co-localized with the infiltrates. Moreover, saliva
      production was reduced, and SS autoantibodies were observed in the serum of these
      mice. Finally, female Opn Tg mice showed more severe disease compared to males.
      Taken together, these data support a role for Opn in SS pathogenesis. We identify
      a new model of spontaneous SS that recapitulates the human disease in terms of
      sex predilection, histopathology, salivary deficits, and autoantibodies. 

PMID- 25572536
TI  - Decreased expression of carbonyl reductase 1 promotes ovarian cancer growth and
      proliferation.
AB  - Carbonyl reductase 1 (CBR1) expression level is related to tumor progression.
      Decreased CBR1 expression is associated with poor prognosis in ovarian cancer. We
      investigated the relationship between CBR1 expression level and malignant
      potential of ovarian cancer. OVCAR-3 cells overexpressing CBR1 or knocked down
      for CBR1 were obtained by transfecting CBR1 plasmid DNA (pDNA) or small
      interfering RNA (siRNA) by electroporation. In vitro cell proliferation and
      invasion were compared between the two cell types. Subcutaneous CBR1
      overexpressed OVCAR-3 cells (n=10) and wild-type ones (n=5) were injected into
      nude mice. The CBR1 siRNA was then injected twice a week into five of the 10 CBR1
      overexpressed OVCAR-3 tumors. Tumor growth and metastatic behavior were observed
      3 weeks after cell transplantation. Cell proliferation significantly decreased in
      CBR1-overexpressed cells as compared to the control, whereas cell proliferation
      and invasion significantly increased in CBR1-suppressed cells as compared to the
      control. The size of the CBR1 siRNA-injected tumors (n=5) increased significantly
      as compared to the other two groups (n=5 for each group). The number of
      metastatic foci in the lungs was significantly higher in mice injected with CBR1
      siRNA (7.0+/-2.0) compared to CBR1-overexpressed and wild-type tumors (0 and
      2.0+/-2.0, respectively). Western blot analysis showed that, while vascular
      endothelial growth factor (VEGF)-C expression was stable in the CBR1-siRNA
      injected tumors, E-cadherin expression was decreased, whereas matrix
      metalloproteinase (MMP)-9 was increased in CBR1-siRNA-injected tumors compared to
      the other two groups. These results showed that CBR1 decreases promoted tumor
      proliferation and growth as well as invasion and metastasis, suggesting that CBR1
      has potential to become a new candidate for molecular targeting therapy.

PMID- 25572535
TI  - Modulation of STAT3 and STAT5 activity rectifies the imbalance of Th17 and Treg
      cells in patients with acute coronary syndrome.
AB  - The signal transducer and activator of transcription (STAT) activity plays an
      important role in the differentiation and imbalance of Th17 and Treg cells in
      acute coronary syndrome (ACS) patients. We determined that the basal STAT3
      phosphorylation level was significantly increased and exhibited a positive
      relationship with Th17 cells but was negatively correlated with Treg cells in ACS
      patients. Opposite effects were observed for STAT5 activity. Using the
      pharmaceutical inhibitor TG101348 or knockdown of STAT3 reduced the number of
      Th17 cells while promoting the number and function of Treg cells via the Janus
      kinase2 (JAK2)/STAT3 pathway in ACS patients. Significantly more STAT5 bound to
      the Foxp3 locus when STAT3 was knocked down, and overexpression of STAT5 led to
      an increased number of Treg cells but a decreased number of Th17 cells in ACS
      patients. Our findings demonstrate that modulation of STAT3/STAT5 activity
      rectifies the imbalance of Th17/Treg cells in ACS patients. 

PMID- 25572537
TI  - MRI findings of olivary degeneration after surgery for posterior fossa tumours in
      children: incidence, time course and correlation with tumour grading.
AB  - PURPOSE: Olivary degeneration is due to many posterior cranial fossa (PCF)
      lesions affecting the dentato-rubro-olivary pathway, also known as Guillain
      Mollaret triangle. Triangle damage results in hyperexcitation and consequently in
      hypertrophy of the inferior olivary nucleus (ION). The aim of our study was to
      evaluate the incidence of magnetic resonance (MR) imaging changes in the ION
      after surgery in a large cohort of paediatric patients and to determine their
      correlation with tumour grade. MATERIALS AND METHODS: We retrospectively
      evaluated 58 patients treated surgically for PCF tumours who underwent MR imaging
      between 2007 and 2014, 1 week to 5 years after surgery. Histopathology revealed
      29 medulloblastomas (WHO IV), 6 ependymomas (WHO II), 2 anaplastic ependymomas
      (WHO III) and 21 pilocytic astrocytomas (WHO I). ION MR imaging changes were
      correlated with surgery-to-MR interval and with tumour grading. RESULTS: ION MR
      imaging changes were observed in 19/64 (33 %), and all consisted of T2 signal
      alterations, 15 bilateral and four unilateral, with dentate nucleus damage in all
      cases. Olivary enlargement was observed in few cases only (7/19). ION T2
      hyperintensity was always present between 1 and 6 months after surgery with a
      trend to decrease, becoming faint after 1 year. The Fisher test demonstrated a
      significant (p = 0.005) correlation between ION MR imaging changes and high
      tumour grade. CONCLUSIONS: Our results demonstrate that olivary degeneration,
      with or without hypertrophy, is a relatively frequent consequence of posterior
      fossa surgery, particularly in children treated for high-grade tumours. Knowledge
      of this condition can prevent misdiagnoses and unnecessary investigations.

PMID- 25572538
TI  - Spontaneous non-aortic retroperitoneal hemorrhage: etiology, imaging
      characterization and impact of MDCT on management. A multicentric study.
AB  - PURPOSE: The purpose of this multicentric study is to assess the usefulness of
      multiphasic Computed tomography in the identification of spontaneous non
      traumatic retroperitoneal hematoma (SRH) and its management, with references to
      the role of interventional radiology. MATERIALS AND METHODS: From January 2011 to
      June 2014, 27 patients with SRH were selected. Patients with aortic, traumatic,
      or iatrogenic source of bleeding were excluded. All the patients were studied
      with multiphasic MDCT after injection of intravenous contrast. Digital
      Subtraction angiography and percutaneous embolization treatment were performed.
      RESULTS: CT identified SRH in all cases (100%), showing the source of bleeding in
      11 cases (40%) and pointing out the source of bleeding in 15 cases (55%). In one
      case (5%), the bleeding origin was recognized only at surgery as adrenal source.
      CT has identified a contrast medium extravasation in the arterial phase in 17
      patients (63%), treated successfully by percutaneous embolization in 13 and by
      open-surgery in two cases. Two patients died before undergoing intervention and
      surgery, respectively. Ten patients (37%) were non-operatively treated
      successfully with clinical, laboratory, and imaging follow-up. CONCLUSIONS:
      Multiphasic CT is the gold standard for the identification of a SRH. Recognition
      of CT signs of active bleeding is the crucial feature influencing the timing of
      therapeutic treatment. Urgent embolization should be performed in cases of
      arterial bleeding or contained vascular injuries supplying the retroperitoneal
      hematoma. Surgery is to be addressed in cases of actively bleeding hematomas
      associated with complication. Finally, an initial more conservative approach can
      be adopted in patients without signs of contrast extravasation or low-flow active
      bleeding. Technical skill, expertise, and recognition of CT signs of arterial
      active bleeding are critical features influencing patients management.

PMID- 25572540
TI  - Cumulative radiation dose and radiation risk from medical imaging in patients
      subjected to endovascular aortic aneurysm repair.
AB  - PURPOSE: This study was undertaken to quantify the cumulative effective dose
      (CED) of radiation and the dose to relevant organs in endovascular aortic repair
      (EVAR) patients, to assess radiation risks and to evaluate the clinical
      usefulness of multi-detector computed tomography (MDCT) follow-up. MATERIALS AND
      METHODS: The radiation exposures were obtained from 71 consecutive EVAR patients
      with a follow-up duration >=1 year. Dose calculations were performed on an
      individual basis and expressed as effective doses and organ doses. Radiation risk
      was expressed as risk of exposure-induced death (%), using the biological effects
      of ionising radiation model. Two radiologists independently assessed the images
      for abdominal aortic aneurysm expansion without endoleaks, thrombotic occlusion,
      endoleaks and device migration. They first reviewed arterial imaging alone and
      subsequently added non-contrast and delayed phases to determine the overall
      performance. RESULTS: The median total CED and annual CED were 224 and 104 mSv
      per patient-year. The median cumulative organ doses were 191, 205, 230, 269 and
      271 mSv for lung, bone marrow, liver, colon and stomach, respectively. The
      average risk of exposure-induced death was 0.8 % (i.e., odds 1 in 130). All the
      findings related to EVAR outcome and leading to a change in patient management
      were visible during the arterial phase of the MDCT angiography. Omission of the
      unenhanced scan and the venous phase of the MDCT angiography would have led to a
      significant reduction of about 60 % of the associated MDCT radiation exposure in
      a single patient. CONCLUSIONS: EVAR patients received high radiation doses and
      the excess cancer risk attributable to radiation exposure is not negligible. The
      unenhanced scan and the venous phase of the MDCT angiography could have been
      omitted without compromising the utility of the examination and with a
      significant reduction of doses and associated risks.

PMID- 25572539
TI  - Secondary prevention at 360 degrees : the important role of diagnostic imaging.
AB  - The aim of this paper is to underline the importance of the role of general
      practitioners (GPs) in distributing vital information about prevention to
      citizens, to highlight the importance of the so-called voluntary prevention
      programmes, both for conditions for which no organised screening programmes exist
      and for those for which they do exist but may well be obsolete or inefficient.
      Nowadays, voluntary prevention is made more effective thanks to the new
      sophisticated diagnostic technologies applied worldwide by diagnostic imaging.
      Epidemiological data about the incidence and causes of death among the Italian
      population have shown that screening programmes should be aimed first at fighting
      the following diseases: prostatic carcinoma, lung cancer, colorectal carcinoma,
      breast cancer, cardiovascular disease, cerebrovascular disease, aortic and
      peripheral vascular disease. GPs do not generally give good or adequate
      instructions concerning voluntary prevention programmes; GPs may not even be
      aware of this type of prevention which could represent a valuable option together
      with the existing mass screening programmes. Therefore, in the following
      analysis, we aim to outline the correct diagnostic pathway for the prevention of
      diseases having the highest incidence in our country and which represent the most
      frequent causes of death. If used correctly, these screening programmes may
      contribute to the success of secondary prevention, limiting the use of tertiary
      prevention and thus producing savings for the Italian National Health System. 

PMID- 25572541
TI  - Fluoroscopy-guided hydrostatic reduction of intussusception in infancy: role of
      pharmacological premedication.
AB  - PURPOSE: Intussusception is one of the most common causes of paediatric
      emergency. Fluoroscopy-guided hydrostatic reduction is a common nonoperative
      management strategy for the treatment of intussusception. The role of
      pharmacological premedication in increasing the success rate of hydrostatic
      reduction is still controversial. The purpose of this study was to verify the
      presence of a possible correlation between pharmacological premedication and the
      percentage of hydrostatic reduction of intussusception in paediatric patients.
      MATERIALS AND METHODS: This study considered children with a diagnosis of
      idiopathic intussusception treated at our hospital between January 2007 and June
      2013. One group of patients underwent hydrostatic reduction by barium enema
      without any preliminary therapy. A second group of patients received
      pharmacological premedication with both a sedative and an anti-oedematous agent
      before the procedure. RESULTS: A total of 398 patients were treated with barium
      enema for therapeutic purposes. In the group of patients who received no
      premedication (n = 254), 165 (65 %) children achieved hydrostatic reduction of
      the intussusception. Among the patients who received pharmacological
      premedication prior to barium enema (n = 144), 122 (85 %) children achieved
      resolution of the intussusception. CONCLUSIONS: Our study shows that the use of
      pharmacological premedication is effective for the reduction of the
      intussusception, as its limit patient stress, fluoroscopic time and radiation
      dose.

PMID- 25572542
TI  - Bowel and mesenteric injuries from blunt abdominal trauma: a review.
AB  - The bowel and the mesentery represent the third most frequently involved
      structures in blunt abdominal trauma after the liver and the spleen. Clinical
      assessment alone in patients with suspected intestinal and/or mesenteric injury
      from blunt abdominal trauma is associated with unacceptable diagnostic delays.
      Multi-detector computed tomography, thanks to its high spatial, time and contrast
      resolutions, allows a prompt identification and proper classification of such
      conditions. The radiologist, in fact, is asked not only to identify the signs of
      trauma but also to provide an indication of their clinical significance,
      suggesting the chance of conservative treatment in the cases of mild and
      moderate, non-complicated or self-limiting injuries and focusing on life
      threatening conditions which may benefit from immediate surgical or
      interventional procedures. Specific and non-specific CT signs of bowel and
      mesenteric injuries from blunt abdominal trauma are reviewed in this paper. 

PMID- 25572543
TI  - Clinical outcome of percutaneous RF-ablation of non-operable patients with liver
      metastasis from breast cancer.
AB  - PURPOSE: Despite improved anti-neoplastic treatment the prognosis for patients
      with liver metastases from metastatic breast cancer remains poor. MATERIALS AND
      METHODS: Thirty-two consecutive patients with metastatic breast cancer treated
      with radiofrequency ablation (RFA) at the Department of Oncology, Herlev
      Hospital, University of Copenhagen, from 1996 to 2010. RESULTS: Time to
      intrahepatic progression was median 11 months (range 1.6-184 months). Median
      survival after first RFA was 33.5 months. Survival at 1, 2 and 3 years was 87, 68
      and 48 %, respectively. The local recurrence rate was 22 %. CONCLUSIONS: In this
      small, highly selected cohort we found RFA safe and efficacious with a low local
      recurrence rate and a median survival above that expected with systemic
      treatment. Our data are in line with previous studies and underscore the need for
      a large prospective study using optimal chemotherapy regimens and RFA/surgery to
      clarify whether intense treatment protocols can prolong survival for certain
      patient groups.

PMID- 25572544
TI  - Preoperative ultrasound features as prognostic factors for patients with
      hepatocellular carcinoma.
AB  - PURPOSE: Ultrasound is the most common imaging tool used to scan the tumours of
      hepatic carcinoma patients. However, very few studies have been performed to
      evaluate ultrasound imaging features for predicting tumour prognosis. Therefore,
      the goal of the current study was to evaluate preoperative ultrasound
      characteristics as prognostic factors that could affect survival rate after liver
      resection for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of
      104 HCC patients who underwent resection were retrospectively reviewed with
      regard to their clinical data, preoperative ultrasound characteristics, and
      survival rate. Preoperative ultrasound parameters included cirrhosis, tumour
      site, size, echo pattern, portal vein thrombosis, intra-tumour blood flow signal,
      peak systolic velocity (V max), and resistance index (RI). The Kaplan-Meier
      method was used to calculate survival. Pre-resection prognostic factors were
      assessed using univariate log-rank test and a multivariate Cox proportional
      hazards model. RESULTS: The median survival was 37 months. The 1-, 3-, and 5-year
      disease-free survival (DFS) rates were 78.85, 53.85, and 26.92 %, respectively,
      and the overall survival (OS) rates at 1, 3, and 5 years were 85.58, 69.23, and
      46.15 %, respectively. On univariate analysis, shorter survival was associated
      with mixed echo pattern, larger tumour size, portal vein thrombus, affluent flow
      signal, and higher V max. Application of the Cox multivariate proportional
      hazards model indicated that tumour size and blood flow signal in the tumours
      were independent prognostic factors. CONCLUSIONS: The overall survival for HCC
      patients undergoing hepatic resection can be stratified on a sonographic basis of
      tumour size and intra-nodular vasculature. These prognostic factors may be useful
      to determine appropriate treatment for HCC patients.

PMID- 25572545
TI  - Tissue gadolinium deposition in hepatorenally impaired rats exposed to Gd-EOB
      DTPA: evaluation with inductively coupled plasma mass spectrometry (ICP-MS).
AB  - PURPOSE: This study was undertaken to quantify tissue gadolinium (Gd) deposition
      in hepatorenally impaired rats exposed to gadolinium ethoxybenzyl
      diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by means of inductively coupled
      plasma mass spectrometry (ICP-MS) and to compare differences in Gd distribution
      among major organs as possible triggers for nephrogenic systemic fibrosis.
      MATERIALS AND METHODS: Five hepatorenally impaired rats (5/6-nephrectomized, with
      carbon-tetrachloride-induced liver fibrosis) were injected with Gd-EOB-DTPA.
      Histological assessment was conducted and Gd content of the skin, liver, kidneys,
      lungs, heart, spleen, diaphragm, and femoral muscle was measured by inductively
      coupled plasma mass spectrometry (ICP-MS) at 7 days after last injection. In
      addition, five renally impaired rats were injected with Gd-EOB-DTPA and the
      degree of tissue Gd deposition was compared with that in the hepatorenally
      impaired rats. RESULTS: ICP-MS analysis revealed significantly higher Gd
      deposition in the kidneys, spleen, and liver (p = 0.009-0.047) in the
      hepatorenally impaired group (42.6 +/- 20.1, 17.2 +/- 6.1, 8.4 +/- 3.2 MUg/g,
      respectively) than in the renally impaired group (17.2 +/- 7.7, 5.4 +/- 2.1, 2.8
      +/- 0.7 MUg/g, respectively); no significant difference was found for other
      organs. In the hepatorenally impaired group, Gd was predominantly deposited in
      the kidneys, followed by the spleen, liver, lungs, skin, heart, diaphragm, and
      femoral muscle. Histopathological investigation revealed hepatic fibrosis in the
      hepatorenally impaired group. CONCLUSIONS: Compared with renally impaired rats,
      tissue Gd deposition in hepatorenally impaired rats exposed to Gd-EOB-DTPA was
      significantly increased in the kidneys, spleen, and liver, probably due to the
      impairment of the dual excretion pathways of the urinary and biliary systems.

PMID- 25572548
TI  - Anti-TNFs in axial spondyloarthritis.
AB  - Since there is no evidence regarding the efficacy of conventional synthetic
      disease modifying anti-rheumatic drugs in the improvement of axial
      spondyloarthritis (SpA), anti-tumor necrosis factors (anti-TNFs) are recommended
      if nonsteroidal anti-inflammatory drugs fail, or in case of high disease
      activity. Anti-TNFs show encouraging data regarding pain reduction, improved
      mobility and quality of life in both ankylosing spondylitis and non-radiographic
      axial spondyloarthritis. However, withdrawal of anti-TNF therapy leads to relapse
      of disease activity in SpA. Moreover, osteoproliferation does not seem to be
      influenced by anti-TNFs. 

PMID- 25572547
TI  - [Cathepsin K antagonists: preclinical and clinical data].
AB  - Cathepsin K, a cysteine protease, is an essential enzyme in degradation of
      collagen type I. Since cathepsin K is relatively specific to osteoclasts, it
      represents a promising candidate for drug development. In the past decades,
      efforts have been made in developing highly potent, selective and orally
      applicable cathepsin K inhibitors. In contrast to balicatib and relacatib, whose
      drug development programmes were stopped due to cutaneous side-effects related to
      limited drug specificity, the more specific cathepsin K inhibitors odanacatib
      (ODN) and ONO-5334 have entered clinical trials. Odanacatib progressively
      increases bone mineral density (BMD) and decreases bone resorption markers in
      postmenopausal women with low BMD. Its clinical efficacy and safety was confirmed
      by several clinical studies but indicates that odanacatib is characterized by a
      resolution-of-effect with increases in bone resorption and rapid decreases in BMD
      following treatment discontinuation. A phase III fracture prevention study in
      postmenopausal women with osteoporosis is currently in the final phase. 

PMID- 25572549
TI  - Reduction of coronary risk factors immediately and 1 year after inpatient
      rehabilitation in a highly motivated patient cohort.
AB  - Adherence to medical advice, driven by high patient motivation, could lead to a
      significant reduction in risk factors during cardiac rehabilitation.During a 1
      year period, 9082 patients were admitted to six cardiac rehabilitation centres. A
      total of 1195 highly motivated subjects were selected based on their reliable
      completion of a survey regarding cardiac risk factors.Study subjects had lower
      risk factors at baseline compared with a contemporary Austrian database. At
      discharge from the rehabilitation programme subjects showed further reductions in
      median weight, low-density lipoprotein cholesterol, blood pressure and resting
      pulse rate (due to increased levels of daily exercise). Smoking also decreased.
      Most of these changes were still significant after 1 year.The risk factors in
      these highly motivated patients were low to begin with and were further reduced
      by an inpatient rehabilitation programme. The content and method of delivery of
      this programme seem to be effective. Efforts should focus on increasing
      motivation. 

PMID- 25572546
TI  - Gene expression changes controlling distinct adaptations in the heart and
      skeletal muscle of a hibernating mammal.
AB  - Throughout the hibernation season, the thirteen-lined ground squirrel (Ictidomys
      tridecemlineatus) experiences extreme fluctuations in heart rate, metabolism,
      oxygen consumption, and body temperature, along with prolonged fasting and
      immobility. These conditions necessitate different functional requirements for
      the heart, which maintains contractile function throughout hibernation, and the
      skeletal muscle, which remains largely inactive. The adaptations used to maintain
      these contractile organs under such variable conditions serves as a natural model
      to study a variety of medically relevant conditions including heart failure and
      disuse atrophy. To better understand how two different muscle tissues maintain
      function throughout the extreme fluctuations of hibernation we performed Illumina
      HiSeq 2000 sequencing of cDNAs to compare the transcriptome of heart and skeletal
      muscle across the circannual cycle. This analysis resulted in the identification
      of 1,076 and 1,466 differentially expressed genes in heart and skeletal muscle,
      respectively. In both heart and skeletal muscle we identified a distinct cold
      tolerant mechanism utilizing peroxisomal metabolism to make use of elevated
      levels of unsaturated depot fats. The skeletal muscle transcriptome also shows an
      early increase in oxidative capacity necessary for the altered fuel utilization
      and increased oxygen demand of shivering. Expression of the fetal gene expression
      profile is used to maintain cardiac tissue, either through increasing myocyte
      size or proliferation of resident cardiomyocytes, while skeletal muscle function
      and mass are protected through transcriptional regulation of pathways involved in
      protein turnover. This study provides insight into how two functionally distinct
      muscles maintain function under the extreme conditions of mammalian hibernation. 

PMID- 25572551
TI  - Commemorating the passing of Prof. Kazuo Akiyama.

PMID- 25572550
TI  - Relief learning is dependent on NMDA receptor activation in the nucleus
      accumbens.
AB  - BACKGROUND AND PURPOSE: Recently, we demonstrated that the nucleus accumbens
      (NAC) is required for the acquisition and expression of relief memory. The
      purpose of this study was to investigate the role of NMDA receptors within the
      NAC in relief learning. EXPERIMENTAL APPROACH: The NMDA receptor antagonist 2
      amino-5-phosphonopentanoic acid (AP-5) was injected into the NAC. The effects of
      these injections on the acquisition and expression of relief memory, as well as
      on the reactivity to aversive electric stimuli, were tested. KEY RESULTS: Intra
      accumbal AP-5 injections blocked the acquisition but not the expression of relief
      memory. Furthermore, reactivity to aversive electric stimuli was not affected by
      the AP-5 injections. CONCLUSION AND IMPLICATION: The present data indicate that
      NMDA-dependent plasticity within the NAC is crucial for the acquisition of relief
      memory.

PMID- 25572552
TI  - Lipid mediators in allergy: Link between human and animal models.

PMID- 25572553
TI  - Secreted phospholipase A2 and mast cells.
AB  - Phospholipase A2s (PLA2s) are a group of enzymes that hydrolyze the sn-2 position
      of phospholipids to release (typically unsaturated) fatty acids and
      lysophospholipids, which serve as precursors for a variety of bioactive lipid
      mediators. Among the PLA2 superfamily, secreted PLA2 (sPLA2) enzymes comprise the
      largest subfamily that includes 11 isoforms with a conserved His-Asp catalytic
      dyad. Individual sPLA2 enzymes exhibit unique tissue and cellular localizations
      and specific enzymatic properties, suggesting their distinct biological roles.
      Recent studies using transgenic and knockout mice for individual sPLA2 isofoms
      have revealed their involvement in various pathophysiological events. Here, we
      overview the current state of knowledge about sPLA2s, specifically their roles in
      mast cells (MCs) in the context of allergology. In particular, we highlight group
      III sPLA2 (PLA2G3) as an "anaphylactic sPLA2" that promotes MC maturation and
      thereby anaphylaxis through a previously unrecognized lipid-orchestrated circuit.

PMID- 25572554
TI  - Prostanoids in allergy.
AB  - Prostanoids, which include prostaglandin and thromboxane, are metabolites of
      arachidonic acid released in various pathophysiological conditions. They induce a
      range of actions mediated through their respective receptors expressed on target
      cells. It has been demonstrated that each prostanoid receptor has multiple
      functions and that the effect of receptor stimulation can vary depending on
      context; this sometimes results in opposing effects, such as simultaneous
      excitatory and inhibitory outcomes. The balance between the production of each
      prostanoid and the expression of its receptors has been shown to be important for
      maintaining homeostasis but also involved in the development of various
      pathological conditions such as allergy. Here, we review the recent findings on
      the roles of prostanoids in allergy, especially focusing on atopic dermatitis and
      asthma. 

PMID- 25572555
TI  - The role of leukotrienes in allergic diseases.
AB  - Leukotrienes (LTs), both LTB4 and the cysteinyl LTs (CysLTs) LTC4, LTD4 and LTE4,
      are implicated in a wide variety of inflammatory disorders. These lipid mediators
      are generated from arachidonic acid via multistep enzymatic reactions through
      which arachidonic acid is liberated from membrane phospholipids through the
      action of phospholipase A2. LTB4 and CysLTs exert their biological effects by
      binding to cognate receptors, which belong to the G protein-coupled receptor
      superfamily. LTB4 is widely considered to be a potent chemoattractant for most
      subsets of leukocytes, whereas CysLTs are potent bronchoconstrictors that have
      effects on airway remodeling. LTs play a central role in the pathogenesis of
      asthma and many other inflammatory diseases. This review will provide an update
      on the synthesis, biological function, and relevance of LTs to the pathobiology
      of allergic diseases, and examine the current and future therapeutic prospects of
      LT modifiers. 

PMID- 25572556
TI  - Role of omega-3 fatty acids and their metabolites in asthma and allergic
      diseases.
AB  - Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA),
      are found naturally in fish oil and are commonly thought to be anti-inflammatory
      nutrients, with protective effects in inflammatory diseases including asthma and
      allergies. The mechanisms of these effects remain mostly unknown but are of great
      interest for their potential therapeutic applications. Large numbers of
      epidemiological and observational studies investigating the effect of fish intake
      or omega-3 fatty acid supplementation during pregnancy, lactation, infancy,
      childhood, and adulthood on asthmatic and allergic outcomes have been conducted.
      They mostly indicate protective effects and suggest a causal relationship between
      decreased intake of fish oil in modernized diets and an increasing number of
      individuals with asthma or other allergic diseases. Specialized pro-resolving
      mediators (SPM: protectins, resolvins, and maresins) are generated from omega-3
      fatty acids such as EPA and DHA via several enzymatic reactions. These mediators
      counter-regulate airway eosinophilic inflammation and promote the resolution of
      inflammation in vivo. Several reports have indicated that the biosynthesis of SPM
      is impaired, especially in severe asthma, which suggests that chronic
      inflammation in the lung might result from a resolution defect. This article
      focuses on the beneficial aspects of omega-3 fatty acids and offers recent
      insights into their bioactive metabolites including resolvins and protectins. 

PMID- 25572558
TI  - Validation of a COPD screening questionnaire and establishment of diagnostic cut
      points in a Japanese general population: the Hisayama study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is highly prevalent
      worldwide. COPD is a treatable disease and it is important to identify COPD
      subjects, highlighting the need for an efficient screening measure. Although the
      COPD screening questionnaire (COPD Population Screener, COPD-PS) was developed as
      a screening tool, its validity is not clear in population-based studies. This
      study determines the validity of the COPD-PS in the general Japanese population.
      METHODS: All registered residents living in the town of Hisayama aged above 40
      were solicited to participate in a health check-up in 2012. All subjects aged 40
      79 without physician-diagnosed asthma or lung resection were recruited, and 2357
      subjects with the COPD-PS recorded and valid spirometry measurements were
      analyzed. Persistent airflow obstruction (AO) was defined by post-bronchodilator
      FEV1/FVC < 0.7. The sensitivity and specificity of the COPD-PS score for
      identifying AO was assessed by logistic regression analysis. RESULTS: The
      prevalence of AO in this population was 6.5%. The overall area under the receiver
      operating characteristic (ROC) curve for the continuous COPD-PS score was 0.748.
      A cut-point of 4-points is recommended, resulting in a sensitivity of 67.1% and
      specificity of 72.9% with an area under the ROC curve of 0.70. The positive
      predictive value was 14.6% and negative predictive value was 97.0%. CONCLUSIONS:
      The COPD-PS appears to be an adequate measure for large scale screening of
      possible airflow obstruction requiring further testing with spirometry.

PMID- 25572557
TI  - Periostin contributes to epidermal hyperplasia in psoriasis common to atopic
      dermatitis.
AB  - BACKGROUND: Epidermal hyperplasia is a histological hallmark observed in both
      atopic dermatitis (AD) and psoriasis, although the clinical features and the
      underlying immunological disorders of these diseases are different. We previously
      showed that periostin, a matricellular protein, plays a critical role in
      epidermal hyperplasia in AD, using a mouse model and a 3-dimensional organotypic
      coculture system. In this study, we explore the hypothesis that periostin is
      involved in epidermal hyperplasia in psoriasis. METHODS: To examine expression of
      periostin in psoriasis patients, we performed immunohistochemical analysis on
      skin biopsies from six such patients. To investigate periostin's role in the
      pathogenesis of psoriasis, we evaluated periostin-deficient mice in a psoriasis
      mouse model induced by topical treatment with imiquimod (IMQ). RESULTS: Periostin
      was substantially expressed in the dermis of all investigated psoriasis patients.
      Epidermal hyperplasia induced by IMQ treatment was impaired in periostin
      deficient mice, along with decreased skin swelling. However, upon treatment with
      IMQ, periostin deficiency did not alter infiltration of inflammatory cells such
      as neutrophils; production of IL-17, -22, or -23; or induction/expansion of IL-17
      and IL-22-producing group 3 innate lymphoid cells. CONCLUSIONS: Periostin plays
      an important role during epidermal hyperplasia in IMQ-induced skin inflammation,
      independently of the IL-23-IL-17/IL-22 axis. Periostin appears to be a mediator
      for epidermal hyperplasia that is common to AD and psoriasis.

PMID- 25572559
TI  - Safety and efficacy of fluticasone furoate nasal spray in Japanese children 2 to
      <15 years of age with perennial allergic rhinitis: a multicentre, open-label
      trial.
AB  - BACKGROUND: Fluticasone furoate nasal spray (FFNS) is a glucocorticoid developed
      for the treatment of allergic rhinitis (AR). This study aimed to assess the
      safety, efficacy, and systemic exposure of FFNS in Japanese children with
      perennial AR (PAR). METHODS: In this multicentre, open-label, phase 3 study, 61
      children aged 2 to <15 years were treated with FFNS 55 MUg, once daily for 12
      weeks. Nasal and ocular symptoms were scored by parents/guardians/patients and
      recorded in a patient's daily diary. In addition, rhinoscopy findings, including
      mucosal swelling, were scored by the investigators as an efficacy measure. As a
      safety measure, adverse events and clinical laboratory data were evaluated.
      RESULTS: An adverse event was reported by 67% of patients during the treatment
      and follow-up period, all of which were mild in intensity. The most commonly
      reported adverse events were nasopharyngitis and acute sinusitis (acute
      rhinosinusitis). There were no serious adverse events. FFNS 55 MUg improved nasal
      symptom scores and rhinoscopy findings compared with the baseline. Ocular symptom
      scores were also improved compared with the baseline in FFNS 55 MUg in a sub
      group of patients with any ocular symptoms at baseline. FFNS 55 MUg was shown to
      be well tolerated over the 12-week treatment period. Majority of patients
      receiving FFNS 55 MUg had unquantifiable plasma levels of fluticasone furoate
      (FF). CONCLUSIONS: Twelve-week treatment with FFNS 55 MUg, once daily, is well
      tolerated and effective with low systemic exposure in Japanese children aged 2 to
      <15 years with PAR.

PMID- 25572560
TI  - Food allergy preceded by contact urticaria due to the same food: involvement of
      epicutaneous sensitization in food allergy.
AB  - BACKGROUND: There have recently been reports suggesting that sensitization to
      food allergens may occur outside the intestinal tract, especially through the
      skin. To clarify the role of epicutaneous sensitization in food allergy, we
      investigated the clinical characteristics of adult patients with food allergies
      preceded by contact urticaria due to the same foods. METHODS: We investigated
      clinical characteristics of 15 patients (20-51 years of age; 5 men and 10 women),
      who had food allergies preceded by contact urticaria. RESULTS: Fourteen patients
      were contact urticaria due to the causative foods during occupationally cooking,
      whereas 1 patient during face pack. In the occupational group, causative foods
      included rice, wheat, fruits, vegetables, fish, shrimp and cuttlefish; in the
      fresh cucumber paste case the cause was cucumber. In the 15 patients, the
      causative foods were fresh, not processed, and were tolerated by most (9/15, 60%)
      after heating. Regarding to symptoms after ingestion of the causative foods, the
      most frequently induced symptoms was oral symptoms (14/15, 93.3%), followed by
      urticaria (4/15, 26.7%), abdominal symptoms (3/15, 20%). The duration between the
      start of jobs or face pack, and the onset of contact urticaria was from 1 month
      to 19 years (mean, 8.7 years). The duration between the onset of contact
      urticaria and the onset of food allergy was from a few weeks to 6 years (mean, 11
      months). One sushi cook experienced severe anaphylactic shock after ingestion of
      fish. In the occupational group, 13 of 15 patients (86.7%) had atopic dermatitis
      or hand eczema, indicating that the impaired skin barrier might be a risk for
      food allergies induced by epicutaneous sensitization. CONCLUSIONS: Epicutaneous
      sensitization of foods could induce food allergy under occupational cooking and
      skin-care treatment with foods in adults.

PMID- 25572561
TI  - Evaluation of airflow limitation using a new modality of lung sound analysis in
      asthmatic children.
AB  - BACKGROUND: Reliable assessment of not only symptoms but also lung function is
      essential in asthma management. We developed a new technology for analyzing lung
      sounds and assessed its clinical usefulness in asthmatic children. METHODS: Forty
      four children underwent lung sound recording with simultaneous airflow
      measurement using a sensor on the upper right anterior chest. We calculated a
      sound parameter index from the amplitude of inspiratory lung sounds at 700 Hz
      (ic700). ic700 were compared depending on flow and body size. In addition, 184
      asthmatic children and 16 non-asthmatic children underwent lung sound analysis
      and lung function test in an asymptomatic state. In the asthma group, 135
      children received treatment continually. The untreated asthma group included 28
      children who had never received treatment continually and 21 children who had not
      been treated for at least 1 year. The asthmatic children were divided into four
      classes according to asthma severity. ic700 were compared depending on
      spirometric parameters and asthma severity classification. RESULTS: The
      influences of flow and body size were negligible for ic700. ic700 correlated with
      FEV1%, MMF and FEF50 (r = -0.436, -0.339 and -0.302, respectively). There was a
      significant difference of ic700 between asthmatic and non-asthmatic children (p <
      0.001), and ic700 correlated with the classification of asthma severity (p <
      0.001). The ic700 scores of the severe group were higher than those of the
      intermittent group and non-asthmatic children. CONCLUSIONS: It was possible to
      evaluate airway dysfunction of asthma using ic700, which was calculated non
      invasively by analyzing lung sounds alone, without measuring body size and
      airflow.

PMID- 25572563
TI  - Increased thrombin generation potential in patients with chronic spontaneous
      urticaria.

PMID- 25572562
TI  - IgE Abs to Der p 1 and Der p 2 as diagnostic markers of house dust mite allergy
      as defined by a bronchoprovocation test.
AB  - BACKGROUND: Limited information is available regarding the clinical usefulness of
      measuring the levels of IgE to allergen components from house dust mites (HDMs)
      in the diagnosis of genuine HDM allergy. METHODS: To evaluate the diagnostic
      usefulness of measuring levels of serum IgE antibodies (Abs) to allergen
      components from Dermatophagoides pteronyssinus (DP) as a predictor of immediate
      asthmatic response (IAR) to bronchoprovocation, we studied 55 DP-sensitized
      asthmatic patients who underwent a bronchoprovocation test using crude DP
      extract. The levels of IgE Abs to crude DP, nDer p 1, rDer p 2, and rDer p 10 in
      patients who showed IAR (n = 41) were compared with those in patients who showed
      no IAR (n = 14). RESULTS: While the frequencies of positivity for IgE Abs to nDer
      p 1 and rDer p 2 among the entire study population were 89 and 86%, respectively,
      all patients with IAR tested positive for both of them with high IgE
      concentrations. The areas under the receiver operating characteristic curves for
      IgE to nDer p 1 and rDer p 2 as predictors of IAR were 0.913 and 0.906,
      respectively. The specificity of IgE to nDer p 1 and rDer p 2 was higher than IgE
      to crude DP even at low cut-off points. CONCLUSIONS: IgE to nDer p 1 and/or rDer
      p 2 was highly predictive of allergen-induced IAR. These findings validate the
      clinical usefulness of measuring the levels of IgE to nDer p 1 and rDer p 2 as a
      diagnostic tool for genuine HDM allergy.

PMID- 25572564
TI  - Fecal eosinophil-derived neurotoxin in cow's milk-sensitive enteropathy: a case
      report.

PMID- 25572565
TI  - Fixed drug urticaria: a report of two patients.

PMID- 25572566
TI  - The relevance of obesity on asthma control in identical twins.

PMID- 25572567
TI  - Colonic involvement in Stevens-Johnson syndrome-like mucositis without skin
      lesions.

PMID- 25572568
TI  - Hypersensitivity reactions and drug fever by bendamustine: a case report of three
      patients.

PMID- 25572569
TI  - Multicentric Castleman's disease with impaired lymphocytic apoptosis.

PMID- 25572570
TI  - Sensitization of specific IgE-positive Japanese who have experienced Hymenoptera
      stings to recombinant versions of the Ves v 1 and Ves v 5 allergens in hornet
      venom.

PMID- 25572572
TI  - The effect of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide on lymphocyte
      subsets and humoral immune response in SRBC-immunized mice.
AB  - 5-Amino-3-methyl-4-isoxazolecarboxylic acid hydrazide is a non-cytotoxic
      synthetic isoxazole derivative with considerable immunomodulatory properties
      demonstrated in in vitro experiments. The aim of this study was to investigate
      the influence of this compound, depending on the dosage and schedule of
      treatment, on lymphocyte subsets in non-immunized mice and humoral immune
      response in SRBC (sheep red blood cells)-immunized mice. An analysis of
      lymphocyte subsets was carried out by flow cytometry, using specific monoclonal
      antibodies stained with fluorescein isothiocyanate (FITC) or phycoerythrin (PE).
      In the SRBC-immunized mice, the influence of the compound on the humoral response
      was determined, depending on the time of administration relative to the antigen.
      The number of plaque forming cells (PFC) was determined by a local hemolysis
      technique in an agar gel. Total and 2-mercaptoethanol resistant serum
      agglutination titers were defined by active hemagglutination test carried out on
      microplates. The investigated hydrazide was able to modulate the percentage and
      absolute number of T lymphocyte subsets in the thymus, and T and B lymphocytes in
      the peripheral lymphatic organs. It also enhanced humoral immune response in SRBC
      immunized mice by increasing the number of cells producing hemolytic anti-SRBC
      antibodies (PFC) and by augmenting the level of total and 2-mercaptoethanol
      resistant hemagglutinin. The present study showed modulatory effects of 5-amino-3
      methyl-4-isoxazolecarboxylic acid hydrazide on lymphocyte subsets and humoral
      immune response in mice. This compound could be potentially useful for the
      treatment of autoimmune diseases, infections or as an adjuvant for boosting the
      efficacy of vaccines. 

PMID- 25572571
TI  - S-1 plus cisplatin with concurrent radiotherapy versus cisplatin alone with
      concurrent radiotherapy for stage III non-small cell lung cancer: a pilot
      randomized controlled trial.
AB  - BACKGROUND: We investigated the efficacy and safety of S-1 and cisplatin with
      concurrent thoracic radiation (SCCR) over cisplatin alone plus concurrent
      thoracic radiation (CCR) for unresectable stage III non-small-cell lung cancer
      (NSCLC). METHODS: Between January 2009 and November 2011, 40 eligible patients
      with NSCLC were included and divided randomly into two groups. Twenty patients
      received SCCR with S-1 (orally at 40 mg/m(2) per dose, b.i.d.) on days 1 through
      14, cisplatin (60 mg/m(2) on day 1) every 4 weeks for two cycles, and
      radiotherapy (60 Gy/30 fractions over 6 weeks) beginning on day 1. Twenty
      subjects received CCR (cisplatin and radiotherapy, the same as for SCCR).
      RESULTS: The 3-year overall response rate was 59.3% and 52.4% for the SCCR and
      CCR groups, respectively, and the difference was statistically significant, while
      the median overall survival was 33 months (range, 4-41 months) and 24 months
      (range, 2-37 months), respectively (P = 0.048). The median progression-free
      survival was 31 months for SCCR (range, 5-39 months), whereas it was 20 months
      (range, 2-37 months) for CCR (P = 0.037). The toxicity profile was similar in
      both groups. CONCLUSION: In summary, we demonstrated that S-1 and cisplatin with
      concurrent thoracic radiation was more effective than cisplatin plus radiotherapy
      in NSCLC patients with acceptable toxicity. TRIAL REGISTRATION: Chinese Clinical
      Trials Register: ChiCTR-TRC-13003997 .

PMID- 25572574
TI  - Primary surgical posterior capsulotomy during phacovitrectomy.

PMID- 25572573
TI  - Epigenetic heterogeneity in HIV-1 latency establishment.
AB  - Despite prolonged antiretroviral therapy, HIV-1 persists as transcriptionally
      inactive proviruses. The HIV-1 latency remains a principal obstacle in curing
      AIDS. It is important to understand mechanisms by which HIV-1 latency is
      established to make the latent reservoir smaller. We present a molecular
      characterization of distinct populations at an early phase of infection. We
      developed an original dual-color reporter virus to monitor LTR kinetics from
      establishment to maintenance stage. We found that there are two ways of latency
      establishment i.e., by immediate silencing and slow inactivation from active
      infection. Histone covalent modifications, particularly polycomb repressive
      complex 2 (PRC2)-mediated H3K27 trimethylation, appeared to dominate viral
      transcription at the early phase. PRC2 also contributes to time-dependent LTR
      dormancy in the chronic phase of the infection. Significant differences in
      sensitivity against several stimuli were observed between these two distinct
      populations. These results will expand our understanding of heterogeneous
      establishment of HIV-1 latency populations. 

PMID- 25572575
TI  - Comment on 'The incidence of serious eye injury in Scotland: a prospective
      study'.

PMID- 25572576
TI  - Response to 'Primary surgical posterior capsulotomy during phacovitrectomy'.

PMID- 25572577
TI  - Four quadrant sclerotomies for uveal effusion syndrome.

PMID- 25572578
TI  - Cranial nerve palsies in childhood.
AB  - We review ocular motor cranial nerve palsies in childhood and highlight many of
      the features that differentiate these from their occurrence in adulthood. The
      clinical characteristics of cranial nerve palsies in childhood are affected by
      the child's impressive ability to repair and regenerate after injury. Thus,
      aberrant regeneration is very common after congenital III palsy; Duane syndrome,
      the result of early repair after congenital VI palsy, is invariably associated
      with retraction of the globe in adduction related to the innervation of the
      lateral rectus by the III nerve causing co-contraction in adduction. Clinical
      features that may be of concern in adulthood may not be relevant in childhood;
      whereas the presence of mydriasis in III palsy suggests a compressive aetiology
      in adults, this is not the case in children. However, the frequency of associated
      CNS abnormalities in III palsy and the risk of tumour in VI palsy can be
      indications for early neuroimaging depending on presenting features elicited
      through a careful history and clinical examination. The latter should include the
      neighbouring cranial nerves. We discuss the impact of our evolving knowledge of
      congenital cranial dysinnervation syndromes on this field. 

PMID- 25572579
TI  - The development and evolution of full thickness macular hole in highly myopic
      eyes.
AB  - PURPOSE: To evaluate the morphological changes before and after the formation of
      a full-thickness macular hole (MH) in highly myopic eyes. PATIENTS AND METHODS:
      Retrospective observational case series. From 2006 to 2013, clinical records of
      patients with MH and high myopia who had optical coherence tomography (OCT)
      before the development of MH were reviewed. All patients had been followed for
      more than 1 year since MH formation to observe the morphological changes.
      RESULTS: Twenty-six eyes of 24 patients were enrolled. The initial OCT images
      could be classified into four types: (1) normal foveal depression with abnormal
      vitreo-retinal relationship (eight cases), (2) macular schisis without detachment
      (six cases), (3) macular schisis with concomitant/subsequent detachment (nine
      cases), and (4) macular atrophy with underlying/adjacent scar (three cases).
      After MH formation, one case in type 1 and one case in type 4 group developed
      retinal detachment (RD). In type 2 group, four cases developed RD at the same
      time of MH formation. The preexisting detachment in type 3 group extended in
      eight cases and improved in one case. Among all the cases, 14 eyes received
      vitrectomy and 7 eyes received gas injection. MH sealed in nine eyes after
      vitrectomy and four eyes by gas injection. CONCLUSION: The study revealed four
      pathways of MH formation in highly myopic eyes. MH from macular schisis tended to
      be associated with detachment. However, the evolution and the results of surgical
      intervention were not always predictable.

PMID- 25572580
TI  - Spectrum of morphological and visual changes due to vitreomacular interface
      disorders encountered in a large consecutive cohort of patients.
AB  - AIM: Identify the incidence of vitreomacular traction (VMT) and frequency of
      reduced vision in the absence of other coexisting macular pathology using a
      pragmatic classification system for VMT in a population of patients referred to
      the hospital eye service. METHODS: A detailed survey of consecutive optical
      coherence tomography (OCT) scans was done in a high-throughput ocular imaging
      service to ascertain cases of vitreomacular adhesion (VMA) and VMT using a
      departmental classification system. Analysis was done on the stages of traction,
      visual acuity, and association with other macular conditions. RESULTS: In total,
      4384 OCT scan episodes of 2223 patients were performed. Two hundred and fourteen
      eyes had VMA/VMT, with 112 eyes having coexisting macular pathology. Of 102
      patients without coexisting pathology, 57 patients had VMT grade between 2 and 8,
      with a negative correlation between VMT grade and number of Snellen lines (r=
      0.61717). There was a distinct cutoff in visual function when VMT grade was
      higher than 4 with the presence of cysts and sub retinal separation and breaks in
      the retinal layers. CONCLUSIONS: VMT is a common encounter often associated with
      other coexisting macular pathology. We estimated an incidence rate of 0.01% of
      VMT cases with reduced vision and without coexisting macular pathology that may
      potentially benefit from intervention. Grading of VMT to select eyes with cyst
      formation as well as hole formation may be useful for targeting patients who are
      at higher risk of visual loss from VMT.

PMID- 25572581
TI  - Response to Fu et al.

PMID- 25572582
TI  - What information can we give to the patient about the risks of strabismus
      surgery.
AB  - I hope to report the type, incidence, and clinical outcomes of severe
      complications from strabismus surgery in the United Kingdom and to help in the
      discussions involved in the consent process. The main part of the talk will
      revolve around a BOSU (British Ophthalmic Survey Unit) investigation. Cases were
      identified prospectively between 1 September 2008 and 31 August 2010.
      Questionnaire data were requested at the time of the complication recognition and
      at 6 months' follow-up. Outcome was graded I-V, with a poor or very poor outcome
      meaning either loss of corrected visual acuity or primary position double vision.
      A total of 60 completed reports of adverse events and complications were received
      during the study period. During the same time, ~24 000 strabismus surgeries were
      carried out in the United Kingdom, yielding an overall incidence of 1 in 400
      operations (95% binomial confidence, 1 per 333-500 operations). The most commonly
      reported complication was perforation of the globe (19 (0.08%)), followed by a
      suspected slipped muscle (16 (0.067%)), severe infection (14 (0.06%)), scleritis
      (6 (0.02%)), and lost muscle (5 (0.02%)). Overall, complications were reported in
      adults and children in equal numbers; however, scleritis was significantly more
      common in adults. A poor or very poor clinical outcome was recorded as 1
      operation per 2400. The study limitations are as follows: the denominator was
      extrapolated from the number of surgeries in England, and there was an almost
      certain underreporting of cases. Complications with the potential for a poor
      outcome are relatively common, but the final clinical outcome is good in the
      majority of cases. 

PMID- 25572583
TI  - Reply to: 'Four quadrant sclerotomies for uveal effusion syndrome'.

PMID- 25572585
TI  - A decade of community-wide efforts in advancing medical image understanding and
      retrieval.

PMID- 25572584
TI  - Patterns of ranibizumab and aflibercept treatment of central retinal vein
      occlusion in routine clinical practice in the USA.
AB  - BACKGROUND: The intravitreal anti-vascular endothelial growth factor treatments
      ranibizumab and aflibercept have proven efficacy in clinical trials, but their
      real world usage in central retinal vein occlusion (CRVO) has not been assessed.
      We therefore evaluated the treatment patterns of both drugs in a US claims
      database. METHODS: The IMS Integrated Data Warehouse was used to identify the
      patients with CRVO in the USA with claims for ranibizumab or aflibercept between
      24 September 2012 and 31 March 2014 with at least 12 months follow-up. Patients
      were required to have had no anti-VEGF treatment code for 6 months before index
      ('treatment-naive'). Mean numbers of injections and non-injection visits to a
      treating physician were compared with patients receiving these treatments.
      RESULTS: Patient characteristics were similar for patients receiving ranibizumab
      (n=206) or aflibercept (n=79) at index. The mean (+/-SD) numbers of injections
      received by patients treated with ranibizumab or aflibercept were 4.4+/-2.8 and
      4.7+/-2.9 (P=0.38), respectively; the total number of patient visits to their
      treating physician was 7.3+/-3.7 and 7.0+/-2.9 (P=0.52), respectively. For
      patients receiving one or more injections (n=238), the mean interval between
      injections was 55.1 days (ranibizumab) and 54.2 days (aflibercept; P=0.44).
      CONCLUSIONS: Our results suggest that, in routine clinical practice, patients
      receive a comparable number of injections in the first year of treatment with
      ranibizumab or aflibercept. This may have implications for commissioning and
      service development of CRVO care pathways.

PMID- 25572586
TI  - Effects of chronic resveratrol supplementation in military firefighters undergo a
      physical fitness test--a placebo-controlled, double blind study.
AB  - PURPOSE: The purpose of this study was to determine the plasma metabolic response
      and certain indicators of oxidative stress (antioxidant system and oxidative
      stress biomarkers) in plasma and erythrocytes of Brazilian military firefighters
      supplemented or not with resveratrol (RES) for 90 days (100 mg/day). The analyses
      were performed before and after a typical physical fitness test (FT) used to
      induce oxidative stress. METHODS/RESULTS: In this placebo-controlled double
      blinded study, we observed that RES supplementation did not present hepatic
      consequences compared with the placebo group following analysis of AST, ALT and
      GGT plasma activities. Plasma glucose and triglycerides levels were increased
      after the FT in firefighters supplemented with RES but were not elevated at
      baseline. Neither total nor cholesterol fractions were modified by RES
      supplementation. CK levels were increased after the firefighters performed the
      FT; however, no differences were determined between the placebo and RES groups.
      Ferric-reducing ability of plasma as well as uric acid was increased after the
      FT, but was not modified by RES supplementation. Plasma oxidative stress
      biomarkers, such as thiol content, 8-isoprostane and 8OHdG, showed no
      modifications, while IL-6 and TNF-alpha were decreased in the RES group after the
      FT. Among antioxidant enzyme activities determined in erythrocytes from the
      firefighters, only GPx activity was reduced by RES supplementation both before
      and after the FT. CONCLUSION: In summary, the most pronounced effect of RES
      supplementation is its anti-inflammatory effect, which reduced IL-6 and TNF-alpha
      level. The FT applied to Brazilian military firefighters was not sufficient to
      challenge the antioxidant defense systems, and, therefore, 100mg of RES for three
      months did not induce significant effects.

PMID- 25572587
TI  - Counting actinic keratosis - is photographic assessment a reliable alternative to
      physical examination in clinical trials?

PMID- 25572588
TI  - [Intensified adjuvant chemotherapy with FOLFOX in the multimodal treatment of
      rectal cancer].

PMID- 25572589
TI  - [Surgical management after embolization of gastrointestinal and abdominal
      bleeding].

PMID- 25572590
TI  - XAGE-1b cancer/testis antigen is a potential target for immunotherapy in prostate
      cancer.
AB  - INTRODUCTION: Gene-modified cell vaccines are now considered to be the best way
      to achieve immunotherapy for a variety of cancers including prostate cancer
      (PCa). XAGE-1b is a member of the cancer/testis antigen family which has
      demonstrated strong immunogenicity. We investigated whether XAGE-1b is an ideal
      target for PCa immunotherapy. MATERIALS AND METHODS: The recombinant eukaryotic
      expression vector pDisplay-XAGE-1b was constructed. Then the recombinant vector
      was transfected into Myc-CaP cells and its immunogenicity in vitro was studied.
      After transfection, the Myc-CaP-XAGE-1b cells were injected into FVB mice
      subcutaneously. Tumor growth was periodically observed and the anti-tumor effect
      and mechanism in vivo were further studied. RESULTS: The recombinant vector was
      correctly constructed by DNA sequencing and restriction endonuclease digestion.
      Myc-CaP cells were successfully transfected with XAGE-1b gene by
      immunofluorescence staining and Western blot. The transfected cells exhibited
      increased IFN-gamma secretion, decreased IL-6 secretion and enhanced killing
      activity. Tumor grew slower in XAGE-1b-modified FVB mice than in wild-type FVB
      mice. High dendritic cell expression and low myeloid-derived suppressor cell
      expression were observed in tumor tissues expressed with XAGE-1b. CONCLUSIONS:
      XAGE-1b gene transfection could significantly enhance the immunogenicity of Myc
      CaP cells. Therefore, XAGE-1b may be an attractive target for antigen-specific
      immunotherapy in PCa.

PMID- 25572592
TI  - Fertility, pregnancies and outcomes reported by females with common variable
      immune deficiency and hypogammaglobulinemia: results from an internet-based
      survey.
AB  - BACKGROUND: Issues of fertility and pregnancy place an extra burden on females
      with primary immunodeficiencies. Patients lack reliable information and providers
      lack guidelines to counsel patients on these anxiety-provoking matters.
      OBJECTIVE: To collate concerns and experiences related to fertility and pregnancy
      from females with humoral immune deficiencies. METHODS: We conducted an internet
      based survey of female patients who self-identified as having a diagnosis of
      primary humoral immune deficiency. RESULTS: Responses from 490 women with common
      variable immune deficiency and 100 with hypogammaglobulinemia were evaluated. The
      reported fertility measure (% of women who had had a birth) was statistically
      significantly lower as compared to the general US population (70 % vs. 85 %, p <
      0.0001) whereas the rates of spontaneous pregnancy loss were comparable. This
      group reported a total of 966 pregnancies; 72 % resulted in a live birth. A
      majority of the pregnancies progressed with no incident and with continuation of
      their IgG replacement therapy; 23 % reported an increase in IgG dosing during
      pregnancy. Only 15 % of those reporting a first pregnancy indicated that they had
      been diagnosed with immune deficiency prior to their first pregnancy; these women
      expressed concern regarding the effect of immune deficiency on their fertility,
      pregnancy and decision to have children. CONCLUSION: With inherent limitations of
      self-reported responses to surveys, females with humoral immune deficiencies
      reported relatively good rates of fertility and pregnancies ending in live
      births. Results of the survey will serve as peer support for patients and inform
      counseling guidelines for providers.

PMID- 25572591
TI  - Circulating tumor cells in newly diagnosed inflammatory breast cancer.
AB  - INTRODUCTION: Circulating tumor cells (CTCs) are an independent prognostic factor
      for progression-free survival (PFS) and overall survival (OS) in patients with
      metastatic breast cancer. Inflammatory breast cancer (IBC) is one of the most
      aggressive forms of breast cancer. The prognostic value of a CTC count in newly
      diagnosed IBC has not been established. The aim of this study was to assess the
      prognostic value of a baseline CTC count in patients with newly diagnosed IBC.
      METHODS: This retrospective study included 147 patients with newly diagnosed IBC
      (77 with locally advanced and 70 with metastatic IBC) treated with neoadjuvant
      therapy or first-line chemotherapy during the period from January 2004 through
      December 2012 at The University of Texas MD Anderson Cancer Center. CTCs were
      detected and enumerated by using the CellSearch system before patients were
      started with chemotherapy. RESULTS: The proportion of patients with >=1 CTC was
      lower among patients with stage III than among patients with metastatic IBC
      (54.5% versus 84.3%; P=0.0002); the proportion of patients with >=5 CTCs was also
      lower for stage III than for metastatic IBC (19.5% versus 47.1%; P=0.0004).
      Patients with fewer than five CTCs had significantly better progression-free
      survival (PFS) (hazard ratio (HR)=0.60; P=0.02) and overall survival (HR=0.59;
      P=0.03) than patients with five or more CTCs. Among patients with stage III IBC,
      there was a nonsignificant difference in PFS (HR=0.66; 95% confidence interval
      (CI), 0.31 to 1.39; P=0.29) and OS (HR=0.54; 95% CI, 0.24 to 1.26; P=0.48) in
      patients with no CTCs compared with patients with one or more CTCs. In
      multivariate analysis, CTC was prognostic for PFS and OS independent of clinical
      stage. CONCLUSIONS: CTCs can be detected in a large proportion of patients with
      newly diagnosed IBC and are a strong predictor of worse prognosis in patients
      with newly diagnosed IBC.

PMID- 25572593
TI  - Emergence of cancer stem cells in hepatocellular carcinoma.

PMID- 25572594
TI  - KSHV-TK: thymidine kinase or tyrosine kinase?

PMID- 25572595
TI  - The diagnostic utility of 99mTc-HMPAO SPECT imaging: a retrospective case series
      from a tertiary referral early-onset cognitive disorders clinic.
AB  - BACKGROUND/AIMS: Patients with early-onset dementia (EOD) often present
      atypically, making an accurate diagnosis difficult. Single-photon emission
      computed tomography (SPECT) provides an indirect measure of cerebral metabolic
      activity and can help to differentiate between dementia subtypes. This study aims
      to investigate the clinical utility of SPECT imaging in the diagnosis of early
      onset Alzheimer's disease. METHODS: All patients attending a tertiary referral
      clinic specialising in EOD between April 2012 and October 2013 were included in
      the study. Statistical analysis of SPECT patterns with clinical diagnoses,
      Addenbrooke's Cognitive Examination version 3 scores, and magnetic resonance
      imaging (MRI) atrophy was undertaken. RESULTS: The results demonstrated a highly
      significant association between SPECT hypoperfusion patterns and clinical
      diagnoses. SPECT changes were demonstrated more frequently than MRI atrophy.
      CONCLUSIONS: The results suggest that SPECT imaging may be a useful adjunct to
      clinical evaluation and a more sensitive biomarker than standard structural
      imaging.

PMID- 25572597
TI  - MesoVATS: video-assisted thoracic surgery partial pleurectomy versus talc
      pleurodesis.

PMID- 25572596
TI  - Grandmother's smoking when pregnant with the mother and asthma in the grandchild:
      the Norwegian Mother and Child Cohort Study.
AB  - BACKGROUND: A trans-generational influence of prenatal tobacco smoke exposure on
      asthma development has been proposed but the evidence remains sparse. METHODS: We
      examined the grandmother's smoking when pregnant with the mother in relation to
      asthma outcomes in the grandchild (current asthma at 36 months (N=53 169,
      cases=3013), current asthma at 7 years (N=25 394, cases=1265) and dispensed
      asthma medications at 7 years in the Norwegian Prescription Database (N=45 607,
      cases=1787)) within the Norwegian Mother and Child Cohort Study (MoBa). We
      calculated adjusted RR (adj. RR) and 95% CIs using log binomial regression.
      RESULTS: A total of 23.5% of mothers reported that their mother smoked when
      pregnant with them. The grandmother's smoking when pregnant with the mother was
      positively associated with asthma at 36 months (adj. RR 1.15 (95% CI 1.06 to
      1.24)), asthma at 7 years (adj. RR 1.21 (95% CI 1.07 to 1.37)) and dispensed
      asthma medications at 7 years (adj. RR 1.15 (95% CI 1.04 to 1.26)). This positive
      association did not differ significantly by the mother's smoking status when
      pregnant with the child (p values for multiplicative interaction >0.1).
      CONCLUSIONS: The grandmother's smoking when pregnant with the mother increased
      the risk of asthma in the grandchild independent of the mother's smoking status.
      However, given limited information on the grandmother's socioeconomic status,
      asthma status and other factors, unmeasured confounding may be present.

PMID- 25572598
TI  - A 63-year-old man with a recurrent right-sided pleural effusion.

PMID- 25572599
TI  - Author's response: Airway anatomy in COPD: many dimensions to consider.

PMID- 25572600
TI  - Cord blood platelet gel treatment of dystrophic recessive epidermolysis bullosa.
AB  - Epidermolysis bullosa (EB) is comprised of a group of hereditary mechanobullous
      disorders that are characterised by extremely fragile skin and mucous membranes.
      This results in blister formation and non-healing wounds. This case report
      describes the results of an innovative treatment of two large skin lesions in a
      newborn with dystrophic recessive EB (DEB) who experienced bacterial
      superinfections and progressive anaemisation. The lesions were treated with
      platelet gels derived from allogeneic cord blood (cord blood platelet gel,
      CBPGs). The skin lesions were clinically evaluated and treated with CBPG weekly
      until they completely healed. The first and second lesion required CBPG
      applications for 2 and 4 weeks, respectively. Both lesions were monitored weekly
      for 6 weeks after the last CBPG application, and no significant relapses were
      observed during the follow-up period. This case indicates that CBPG is an
      effective and safe therapeutic option for managing newborns with DEB,
      particularly as treatment and prevention of fluid loss and superinfection.

PMID- 25572601
TI  - Role of susceptibility-weighted imaging in demonstration of cerebral fat
      embolism.
AB  - Cerebral fat embolism (CFE) is a rare but potentially lethal complication of long
      bone fractures. Many cases of CFE occur as subclinical events and remain
      undiagnosed. We report a case of a 22-year-old man, with multiple long bone
      fractures from a road traffic accident, who subsequently developed hypoxia,
      neurological abnormality and petechial rash. CT of the head was normal. MRI of
      the head confirmed the diagnosis with lesions markedly conspicuous and most
      widespread on susceptibility-weighted imaging as compared to all other sequences
      including diffusion-weighted imaging. 

PMID- 25572602
TI  - Chilaiditi's syndrome as a cause for shock.

PMID- 25572603
TI  - Sphincter sparing resection of a large obstructive distal rectal gastrointestinal
      stromal tumour after neoadjuvant therapy with imatinib (Glivec).
AB  - Gastrointestinal stromal tumours (GISTs) are generally rare but are known to be
      the most common mesenchymal tumours of the gastrointestinal tract. We present a
      case of a patient who presented with persistent obstructive gastrointestinal and
      urological symptoms, a sense of incomplete evacuation and bleeding per rectum. A
      colonoscopy was performed and a biopsy was taken of a submucosal mass in the
      distal rectum that revealed a GIST with positive KIT immunostaining. A positron
      emission tomography (PET)/CT scan showed a large metabolically active distal
      rectal tumour of 8 cm with macroscopic invasion of surrounding structures.
      Neoadjuvant therapy with receptor tyrosine kinase inhibitor imatinib (400 mg
      orally daily) was initiated and an excellent partial response consisting of a
      significant decrease in the size of the tumour with complete metabolic resolution
      was observed within 3 months. Six months after initiation of the neoadjuvant
      therapy a rectum resection with manual side-to-end coloanal anastomosis was
      performed. Pathology showed a GIST of 5 cm located 0.1 cm from the distal section
      plane. Our case shows that in patients with a large invasive distal rectal GIST,
      neoadjuvant imatinib therapy can facilitate anal sphincter sparing surgery.

PMID- 25572605
TI  - "Mild dysglycemia" in type 2 diabetes: to be neglected or not?
AB  - "Mild dysglycemia" in type 2 diabetes can be defined by the range of HbA1c
      levels>=6.5% (48 mmol/mol) and<7% (53 mmol/mol), which corresponds to when the
      risk for vascular complications begins to increase. This "mild dysglycemia" is
      characterized by both a dawn phenomenon (a spontaneous blood glucose rise in the
      early morning) and an excess of post-prandial glucose excursions in the absence
      of abnormal elevation in basal glucose, especially during nocturnal periods. This
      represents an intermediary stage between pre-diabetes (HbA1c>=5.7%, 39 mmol/mol,
      and<6.5%, 48 mmol/mol) and those who begin to show a steadily progressive
      worsening in basal glucose (HbA1c>=7%, 53 mmol/mol). Should this relatively minor
      intermediate dysglycemic phase deserve more attention, that is the question. The
      now available incretin-based therapies, and more specifically the DPP-4
      inhibitors provide the clinician with the possibility to reduce or eradicate both
      the dawn phenomenon and post-meal glucose excursions with minimal side effects.
      The availability of 24-h glycemic profiles in those with "mild dysglycemia" will
      help to describe their individual glycemic phenotype, based on which the early
      and appropriate life style changes and/or pharmacological interventions can be
      introduced.

PMID- 25572604
TI  - Teenage acne and cancer risk in US women: A prospective cohort study.
AB  - BACKGROUND: Acne reflects hormone imbalance and is a key component of several
      systemic diseases. We hypothesized that diagnosis of acne as a teenager might
      predict subsequent risk of hormone-related cancers. METHODS: We followed 99,128
      female nurses in the Nurses' Health Study II cohort for 20 years (1989-2009) and
      used Cox proportional hazards models to estimate the hazard ratios (HRs) of 8
      specific cancers (breast, thyroid, colorectal, ovarian, cervical, and endometrial
      cancers, melanoma, and non-Hodgkin lymphoma) for women with a history of severe
      teenage acne. RESULTS: After thoroughly adjusting for the previously known risk
      factors for each cancer, we found that among women with a history of severe
      teenage acne, the relative risk increased, with a multivariable-adjusted HR of
      1.44 (95% confidence interval [CI], 1.03-2.01) for melanoma. We replicated this
      association in an independent melanoma case-control study of 930 cases and 1026
      controls (multivariable-adjusted odds ratio, 1.27; 95% CI, 1.03-1.56). We also
      found that in both studies the individuals with teenage acne were more likely to
      have moles (52.7% vs 50.1%, P < .001 in the cohort study; and 55.2% vs 45.1%, P =
      .004 in the case-control study). CONCLUSIONS: Our findings suggest that a history
      of teenage acne might be a novel risk factor for melanoma independent from the
      known factors, which supports a need for continued investigation of these
      relationships.

PMID- 25572607
TI  - Immunosuppressive therapy for transplant-ineligible aplastic anemia patients.
AB  - Aplastic anemia is a rare life-threatening bone marrow failure that is
      characterized by bicytopenia or pancytopenia in the peripheral blood and a
      hypoplastic or aplastic bone marrow. The patients are at risk of infection and
      hemorrhage due to neutropenia and thrombocytopenia and suffer from symptoms of
      anemia. The main treatment approaches are allogeneic stem cell transplantation
      and immunosuppression. Here, we review current standard immunosuppression and the
      attempts that have been made in the past two decades to improve results: review
      of recent developments also reveals that sometimes not only the advent of new
      drugs, good ideas and well-designed clinical trials decide the progress in the
      field but also marketing considerations of pharmaceutical companies. Aplastic
      anemia experts unfortunately had to face the situation that efficient drugs were
      withdrawn simply for marketing considerations. We will discuss the current
      options and challenges in first-line treatment and management of relapsing and
      refractory patients with an emphasis on adult patients. Some promising new
      approaches are currently under investigation in prospective, randomized trials. 

PMID- 25572606
TI  - HIGHLY METHYL ESTERIFIED SEEDS is a pectin methyl esterase involved in embryo
      development.
AB  - Homogalacturonan pectin domains are synthesized in a highly methyl-esterified
      form that later can be differentially demethyl esterified by pectin methyl
      esterase (PME) to strengthen or loosen plant cell walls that contain pectin,
      including seed coat mucilage, a specialized secondary cell wall of seed coat
      epidermal cells. As a means to identify the active PMEs in seed coat mucilage, we
      identified seven PMEs expressed during seed coat development. One of these,
      HIGHLY METHYL ESTERIFIED SEEDS (HMS), is abundant during mucilage secretion,
      peaking at 7 d postanthesis in both the seed coat and the embryo. We have
      determined that this gene is required for normal levels of PME activity and
      homogalacturonan methyl esterification in the seed. The hms-1 mutant displays
      altered embryo morphology and mucilage extrusion, both of which are a consequence
      of defects in embryo development. A significant decrease in the size of cells in
      the embryo suggests that the changes in embryo morphology are a consequence of
      lack of cell expansion. Progeny from a cross between hms-1 and the previously
      characterized PME inhibitor5 overexpression line suggest that HMS acts
      independently from other cell wall-modifying enzymes in the embryo. We propose
      that HMS is required for cell wall loosening in the embryo to facilitate cell
      expansion during the accumulation of storage reserves and that its role in the
      seed coat is masked by redundancy.

PMID- 25572608
TI  - Computational photochemistry of the azobenzene scaffold of Sudan I and Orange II
      dyes: excited-state proton transfer and deactivation via conical intersections.
AB  - We employed the complete active space self-consistent field (CASSCF) and its
      multistate second-order perturbation (MS-CASPT2) methods to explore the
      photochemical mechanism of 2-hydroxyazobenzene, the molecular scaffold of Sudan I
      and Orange II dyes. It was found that the excited-state intramolecular proton
      transfer (ESIPT) along the bright diabatic (1) pipi* state is barrierless and
      ultrafast. Along this diabatic (1) pipi* relaxation path, the system can jump to
      the dark (1) npi* state via the (1) pipi*/(1) npi* crossing point. However, ESIPT
      in this dark state is largely inhibited owing to a sizeable barrier. We also
      found two deactivation channels that decay (1) pipi* keto and (1) npi* enol
      species to the ground state via two energetically accessible S1 /S0 conical
      intersections. Finally, we encountered an interesting phenomenon in the excited
      state hydrogen-bonding strength: it is reinforced in the (1) pipi* state, whereas
      it is reduced in the (1) npi* state. The present work sets the stage for
      understanding the photophysics and photochemistry of Sudan I-IV, Orange II,
      Ponceau 2R, Ponceau 4R, and azo violet. 

PMID- 25572609
TI  - Diseases of livestock in the Pacific Islands region: setting priorities for food
      animal biosecurity.
AB  - Most Pacific Island countries and territories (PICTs) have developing economies
      and face a critical shortage of veterinarians with limited financial resources
      allocated to their animal disease surveillance programmes. Thus, animal health
      authorities have to set priorities for better focusing their scarce resources.
      The main objective of this study was to identify animal diseases perceived to be
      of importance by decision makers within selected PICTs, at the regional and
      national levels, to ensure better targeting of animal health resources. A second
      objective was to investigate whether the targeted surveillance programmes
      resulting from this rationalized approach would also benefit the local
      communities engaged in livestock production. A multi-criteria prioritization
      process was developed, involving local experts, to score and rank 132 animal
      diseases based on their priority at the regional and national levels for four
      PICTs: Fiji, Papua New Guinea, Solomon Islands, and Vanuatu, which form part of a
      regional Food Animal Biosecurity Network. In parallel interviews with farmers and
      field animal health and production workers were conducted to assess their
      perception of animal diseases. The list of the top-twenty ranked diseases for the
      Pacific Islands region shows a mix of endemic zoonotic diseases (such as
      leptospirosis ranked first; brucellosis third; tuberculosis sixth; and
      endoparasites and ectoparasites, respectively eleventh and thirteenth) with
      exotic diseases (such as HPAI ranked second, FMD fifth, and rabies ninth). There
      were different disease ranking lists for each of the four targeted PICTs,
      confirming different strategies of disease prevention and control may be required
      for each country, rather than a regional approach. Interviewed animal health and
      production workers were unfamiliar with most of the prioritized diseases and a
      majority acknowledged that they would not be able to recognize clinical signs if
      outbreaks were to occur in their area. Leptospirosis, which is endemic and
      identified as the top priority disease at the regional level, was never mentioned
      by any interviewed farmer. Farmers did not name any emerging infectious diseases
      as priorities. Instead, they identified endemic diseases (parasites, flu,
      coccidiosis, and scabies) as the most important. While animal disease priorities
      appear to differ widely between the targeted regions and countries, it also
      varies significantly between experts and farmers. Better targeted surveillance
      programmes may thus result in more rational and transparent allocation of
      resources, and thus enhanced food security, but may not directly match the needs
      of the local communities. 

PMID- 25572611
TI  - Evaluation of the prevalence and specificities of asymptomatic paranasal sinus
      aspergillosis: retrospective study of 59 cases.
AB  - STUDY OBJECTIVES: To calculate the prevalence of asymptomatic localized paranasal
      sinus aspergillosis (or fungus ball) in the general population and to compare
      asymptomatic and symptomatic fungus balls (FB) in order to determine their
      specificities. MATERIAL AND METHOD: Retrospective study including 59 patients
      operated for FB between 2006 and 2011 in a single unit. Patients were divided
      into two groups: asymptomatic patients (group 1, n=10), and symptomatic patients
      (group 2, n=49). All patients in group 1 were identified by systematic screening
      for a site of infection prior to cataract surgery during this period (n=6198).
      All patients were treated by endonasal surgery. Calculation of the prevalence of
      asymptomatic FB was based on standardization of the source population (normal
      distribution, 95% confidence interval). The two groups were then compared
      (clinical context, age, history of root canal treatment, topography, recurrence
      rate), after randomization test by Student's test and Chi(2) test. RESULTS: The
      prevalence rate of asymptomatic FB in our study was 1.6/1000 in the population
      over the age of 55 years. A statistically significant difference was demonstrated
      between the two groups in terms of the following parameters: more advanced age
      for patients of group 1, constant history of root canal treatment in group 1,
      constant maxillary topography in group 1, and higher recurrence rate in group 2.
      Mean follow-up was 18.7 months (range: 3-49 months). DISCUSSION: This study, the
      first to determine the prevalence of asymptomatic FB, suggests the existence of
      very slowly progressive, minimally symptomatic forms, raising the problem of the
      surgical indications in these patients. CONCLUSION: The prevalence of
      asymptomatic fungus balls is 1.6/1000. Prospective studies are necessary to
      justify conservative management in these patients.

PMID- 25572610
TI  - Disk covering methods improve phylogenomic analyses.
AB  - MOTIVATION: With the rapid growth rate of newly sequenced genomes, species tree
      inference from multiple genes has become a basic bioinformatics task in
      comparative and evolutionary biology. However, accurate species tree estimation
      is difficult in the presence of gene tree discordance, which is often due to
      incomplete lineage sorting (ILS), modelled by the multi-species coalescent.
      Several highly accurate coalescent-based species tree estimation methods have
      been developed over the last decade, including MP-EST. However, the running time
      for MP-EST increases rapidly as the number of species grows. RESULTS: We present
      divide-and-conquer techniques that improve the scalability of MP-EST so that it
      can run efficiently on large datasets. Surprisingly, this technique also improves
      the accuracy of species trees estimated by MP-EST, as our study shows on a
      collection of simulated and biological datasets.

PMID- 25572612
TI  - Endothelin-1 and endothelin B receptor expression in pancreatic adenocarcinoma.
AB  - BACKGROUND: Endothelin-1 (ET-1) acting through endothelin A and B receptors (ETAR
      and ETBR) has been implicated in the development of cancer. The endothelin axis
      has not previously been characterised in human pancreatic adenocarcinoma (PAC).
      METHODS: Expression of ET-1, ETAR, ETBR, vascular endothelial growth factor and
      microvessel density (MVD) was determined by immunohistochemistry in 45 surgically
      resected human PACs and 15 non-cancer human pancreas samples. RESULTS: PAC had
      the highest staining intensity for ET-1 and ETBR: 38% PAC samples scored 2+ or
      more compared with 7% non-cancer sample in ET-1; 58% PAC samples scored 2+
      compared with 0% non-cancer samples in ETBR. MVD was significantly lower in PAC
      compared with non-cancer tissue (p<0.0001). CONCLUSIONS: PAC was characterised by
      greater expression of ET-1 and ETBR compared with normal pancreas.

PMID- 25572613
TI  - Patient with an SLC26A4 gene mutation who had low-frequency sensorineural hearing
      loss and endolymphatic hydrops.
AB  - OBJECTIVE: To report magnetic resonance imaging findings in a patient with an
      SLC26A4 gene mutation who had low-frequency sensorineural hearing loss. CASE
      REPORT: A 13-year-old girl had bilateral and symmetric low-frequency
      sensorineural hearing loss. Upon genetic testing, a heterozygous c.1105A > G
      (p.K369E) mutation of the SLC26A4 gene was detected. Mild endolymphatic hydrops
      in the right cochlea and marked endolymphatic hydrops in the left vestibulum were
      seen by magnetic resonance imaging 4 hours after an intravenous gadolinium
      injection. CONCLUSION: This is the first reported case of a patient with the
      SLC26A4 gene mutation c.1105A > G (p.K369E) who had low-frequency sensorineural
      hearing loss. Co-occurrence of cochlear and vestibular endolymphatic hydrops
      suggests an association with that pathology.

PMID- 25572615
TI  - Glypican-3 promotes epithelial-mesenchymal transition of hepatocellular carcinoma
      cells through ERK signaling pathway.
AB  - Glypican-3 (GPC3), a membrane-associated heparan sulfate proteoglycan, is
      frequently upregulated in hepatocellular carcinoma (HCC). However, how GPC3
      contributes to the progress of HCC is largely unclear. The present study
      investigated the association between GPC3 expression and HCC clinicopathological
      characteristics, and particularly focused on the role and underlying mechanisms
      of GPC3 in HCC epithelial-mesenchymal transition (EMT). Remarkably elevated
      expression of GPC3 was demonstrated in HCC tumor tissues compared with paired non
      tumor tissues in 45 patients with HCC by quantitative real-time PCR,
      immunohistochemistry, and western blotting, respectively. Furthermore, the tissue
      expression of GPC3 was increased during HCC progression from Barcelona Clinic
      Liver Cancer stage A or B to stage C. The enhanced levels of GPC3 in HCC tumor
      tissues were tightly correlated to the expression of the EMT-associated proteins
      and tumor vascular invasion. Patients with GPC3-high expression in tumor tissues
      displayed significantly shorter survival time than those with GPC3-low expression
      (P=0.001). Consistent with the findings in patients, HepG2 cells, which expressed
      high levels of GPC3, showed stronger capacity of migration and significant EMT
      like changes when compared to those HCC cells with low levels of GPC3, e.g.,
      Hep3B and Huh7 in scratch, Transwell assays and western blotting. Furthermore,
      administration with exogenous GPC3 in HCC cells activated extracellular signal
      regulated kinase (ERK) and significantly enhanced cell migration and invasion.
      The behavior was significantly inhibited by the ERK inhibitor PD98059. Together,
      our studies show that GPC3 contributes to HCC progression and metastasis through
      impacting EMT of cancer cells, and the effects of GPC3 are associated with ERK
      activation.

PMID- 25572616
TI  - Norcantharidin inhibits lymphangiogenesis by downregulating the expression of
      VEGF-C and VEGF-D in human dermal lymphatic endothelial cells in vitro.
AB  - AIMS: To investigate the effects of norcantharidin on the growth and migration of
      human dermal lymphatic endothelial cells (HDLECs) and further characterize its
      effect on lymphangiogenesis. METHODS: A 3-dimensional fibrin gel
      lymphangiogenesis model was built. Flow cytometry was used to analyze the rate of
      apoptosis and necrosis. RT-PCR, immunohistochemistry and immunoblotting assays
      were used to examine the effect of norcantharidin on vascular endothelial growth
      factor C (VEGF-C), VEGF-D and VEGF receptor 3 during in vitro lymphangiogenesis.
      RESULTS: Norcantharidin caused a marked dose and time-dependent inhibition of the
      growth of HDLECs with an IC50 of 40 nmol/l. The apoptotic rate of HDLECs was
      13.21 +/- 1.60% 24 h after treatment with 7.5 nmol/l norcantharidin and 42.34 +/-
      3.80% with 90 nmol/l norcantharidin (p < 0.01 vs. controls in both). Fibrin gel
      assays showed that norcantharidin (15 nmol/l) reduced the number of tubular
      structures from 68.4 +/- 5.2 in untreated controls to 10.9 +/- 2.3 (p = 0.000).
      RT-PCR, immunohistochemistry and immunoblotting assays showed norcantharidin
      markedly reduced the expression of VEGF-C and VEGF-D. CONCLUSION: Norcantharidin
      inhibits lymphangiogenesis by downregulating the expression of VEGF-C and VEGF-D,
      suggesting that norcantharidin could be an effective agent for targeting
      neolymphangiogenesis.

PMID- 25572617
TI  - Curbing the tobacco epidemic: Employing behavioral strategies or rearranging the
      deckchairs on the Titanic?
AB  - Henningfield brilliantly dissected the deadly comprehensive tactics of the
      tobacco industry but Food and Drug Administration and WHO strategies against the
      tobacco epidemic must be questioned. The Food and Drug Administration has the
      authority to regulate tobacco production (2009 Tobacco Control Act) but fails to
      ban menthol and reduce cigarettes nicotine content. As little has changed, the
      Healthy People 2010 objective of reducing the prevalence of cigarette smoking
      among adults to 12% by 2010 in the US will be attained by 2030. The monitoring of
      the WHO Framework Convention on Tobacco Control (WHO FCTC) is passive, even when
      governments repeatedly violate the Article 5.3 of the Convention, which
      specifically requires protecting public policy from tobacco industry
      interference. Since 2004, the year after the adoption of the Convention, the
      prevalence of daily smoking has leveled off and the 2012 annualized rate of
      change in prevalence of daily smoking was almost null. This contrasts with a 2%
      annual decrease in the prevalence of daily smoking from 1980 to 2004. The tobacco
      endgame needs acts, not bureaucracies. Two counties have been moving forward,
      Brazil has banned menthol and Australia has implemented plain packaging. 

PMID- 25572614
TI  - Alpha-lipoic acid protects against cerebral ischemia/reperfusion-induced injury
      in rats.
AB  - It is well established that the brain is sensitive to ischemia/reperfusion (I/R)
      induced injury. alpha-lipoic acid (LA), a free radical scavenger and antioxidant,
      has a neuroprotective effect against cerebral I/R-induced injury, however, the
      underlying mechanisms remain to be elucidated. Therefore, the present study was
      undertaken to evaluate whether LA was able to protect against cerebral I/R
      induced injury and to examine the potential mechanisms. The neuroprotective
      effects of LA were investigated in a rat model of transient focal ischemia
      induced by middle cerebral artery occlusion (MCAO) followed by reperfusion. Adult
      male Sprague-Dawley rats were randomly assigned into the sham, cerebral I/R
      injury model and model plus LA groups. Cerebral I/R injury was induced by 90 min
      MCAO followed by reperfusion for 24 h. Cerebral infarct size was detected by
      2,3,5-triphenyltetrazolium chloride staining. Neurological deficit score (NDS),
      brain water content and oxidative parameters, including malondialdehyde (MDA),
      nitric oxide (NO), total antioxidant capacity (T-AOC) and superoxide dismutase
      (SOD) were measured. The expression of cleaved caspase-3, brain-derived
      neurotrophic factor (BDNF), phosphatidylinositol-4,5-bisphosphate 3-kinase
      (PI3K), p-Akt and phosphorylated extracellular signal-regulated kinase 1/2 (p
      ERK1/2) were also analyzed using western blotting. The present study demonstrated
      that pretreatment with LA significantly decreased the infarction size, brain
      water content and improved NDS. LA reversed the levels of oxidative parameters,
      including MDA, NO, T-AOC and SOD to their normal state in rat brains following
      cerebral I/R. Furthermore, the expression of cleaved caspase-3 markedly decreased
      and the expression of BDNF, PI3K, p-Akt and p-ERK1/2 significantly increased
      following administration of LA. On the basis of these findings, it was concluded
      that LA protected the brain from cerebral I/R damage by attenuation of oxidative
      stress and caspase-dependent apoptosis. Furthermore, LA exerts its
      neuroprotective effects potentially through activation of the BDNF-PI3K/Akt
      ERK1/2 pathway.

PMID- 25572618
TI  - A randomised controlled trial of an online theory-based intervention to improve
      adult Australians' sun-protective behaviours.
AB  - OBJECTIVE: To evaluate the effectiveness of a single-session online theory of
      planned behaviour (TPB)-based intervention to improve sun-protective attitudes
      and behaviour among Australian adults. METHODS: Australian adults (N=534; 38.7%
      males; Mage=39.3 years) from major cities (80.9%), regional (17.6%) and remote
      areas (1.5%) were recruited and randomly allocated to an intervention (N=265) and
      information only group (N=267). The online intervention focused on fostering
      positive attitudes, perceptions of normative support, and control perceptions for
      sun protection. Participants completed questionnaires assessing standard TPB
      measures (attitude, subjective norm, perceived behavioural control, intention,
      behaviour) and extended TPB constructs of group norm (friends, family), personal
      norm, and image norm, pre-intervention (Time 1) and one week (Time 2) and one
      month post-intervention (Time 3). Repeated Measures Multivariate Analysis of
      Variance tested intervention effects across time. RESULTS: Intervention
      participants reported more positive attitudes towards sun protection and used sun
      protective measures more often in the subsequent month than participants
      receiving information only. The intervention effects on control perceptions and
      norms were non-significant. CONCLUSIONS: A theory-based online intervention
      fostering more favourable attitudes towards sun safety can increase sun
      protection attitudes and self-reported behaviour among Australian adults in the
      short term.

PMID- 25572619
TI  - Evidence from interventions based on theoretical models for lifestyle
      modification (physical activity, diet, alcohol and tobacco use) in primary care
      settings: A systematic review.
AB  - OBJECTIVE: To determine the effectiveness of health promotion interventions based
      on theoretical models of behavioral change to modify the main lifestyle factors
      (physical activity, diet, alcohol and tobacco) in adults receiving primary health
      care (PHC). METHODS: We searched the MEDLINE and Cochrane Database of Systematic
      Reviews from January 2000 to December 2012. Two reviewers independently performed
      the first screening of titles and abstracts, the methodological quality
      assessment using the lecturacritica.com tool, and the extraction of necessary
      data to systematize the available information. RESULTS: Only few studies met the
      inclusion criteria (17 studies from 30 articles). Thirteen were randomized
      controlled trials, three systematic reviews, and one observational study. The
      transtheoretical model was the most frequent (13 studies), and obtained strong
      evidence of its effectiveness for dietary interventions in the short-term and for
      smoking cessation interventions in the long-term as compared to usual PHC
      practice. Limited evidence was found for smoking cessation interventions based in
      the social cognitive theory. CONCLUSION: There are few studies that explicitly
      link intervention strategies and theories of behavioral change. A rigorous
      evaluation of the theoretical principles could help researchers and practitioners
      to understand how and why interventions succeed or fail.

PMID- 25572620
TI  - Efficacy of a tobacco quitline among adult cancer survivors.
AB  - OBJECTIVE: The purpose of the study (conducted 2010-2013) was to determine the
      efficacy of two common types of tobacco quitlines in adult cancer survivors who
      regularly smoked cigarettes. METHOD: Adult onset cancer survivors in Memphis,
      Tennessee (n=427, 67% female, 60% Caucasian) were randomized either to a
      Proactive (i.e., counselor-initiated calls) or Reactive (i.e., participant
      initiated calls) quitline. Both conditions also received nicotine replacement
      therapy. The primary outcome was biochemically-verified (i.e., salivary cotinine)
      smoking cessation. RESULTS: While 12-month self-reported abstinence was
      consistent with other published studies of smoking cessation (22% and 26% point
      prevalence abstinence for Proactive and Reactive conditions, respectively), 48%
      of participants who were tested for cotinine failed biochemical verification,
      indicating a considerable falsification of self-reported cessation. Adjusted
      cessation rates were less than 5% in both intervention conditions. CONCLUSION:
      Our results are consistent with other studies indicating that traditional smoking
      cessation interventions are ineffective among cancer survivors. Moreover, self
      reports of cessation were unreliable in cancer survivors participating in a
      quitline intervention, indicating that future studies should include biochemical
      verification. Given the importance of smoking cessation among cancer survivors
      and low cessation rates in the current study, it may be necessary to design
      alternative interventions for this population. ClinicalTrials.gov identifier:
      NCT00827866.

PMID- 25572621
TI  - The association of physical activity with all-cause, cardiovascular, and cancer
      mortalities among older adults.
AB  - OBJECTIVE: To evaluate the association of physical activity with all-cause,
      cardiovascular, and cancer mortalities among older adults. METHODS: A study
      sample consisting of 77,541 community-dwelling Taipei citizens aged >= 65 years
      was selected based on data obtained from the government-sponsored Annual
      Geriatric Health Examination Program between 2006 and 2010. Subjects were asked
      how many times they had physical activity for >= 30 min during the past 6 months.
      Mortality was determined by matching cohort identifications with national death
      files. RESULTS: Compared to subjects with no physical activity, those who had 1-2
      times of physical activity per week had a decreased risk of all-cause mortality
      [hazard ratio (HR): 0.77; 95% confidence interval (CI): 0.71-0.85). Subjects with
      3-5 times of physical activity per week had a further decreased risk of all-cause
      mortality (HR: 0.64; 95% CI: 0.58-0.70). An inverse dose-response relationship
      was observed between physical activity and all-cause, cardiovascular, and cancer
      mortality. According to stratified analyses, physical activity was associated
      with a decreased risk of mortality in most subgroups. CONCLUSIONS: Physical
      activity had an inverse association with all-cause, cardiovascular, and cancer
      mortality among older adults. Furthermore, most elderly people can benefit from
      an active lifestyle.

PMID- 25572622
TI  - Public awareness of and support for infrastructure changes designed to increase
      walking and biking in Los Angeles County.
AB  - OBJECTIVE: Policies to promote active transportation are emerging as a best
      practice to increase physical activity, yet relatively little is known about
      public opinion on utilizing transportation funds for such investments. This study
      sought to assess public awareness of and support for investments in walking and
      biking infrastructure in Los Angeles County. METHOD: In the fall of 2013, the Los
      Angeles County Department of Public Health conducted a telephone survey with a
      random sample of registered voters in the region. The survey asked respondents to
      report on the presence and importance of walking and biking infrastructure in
      their community, travel behaviors and preferences, and demographics. RESULTS: One
      thousand and five interviews were completed (response rate 20%, cooperation rate
      54%). The majority of participants reported walking, biking, and bus/rail
      transportation investments as being important. In addition, participants reported
      a high level of support for redirecting transportation funds to active
      transportation investment - the population average was 3.28 (between 'strongly'
      and 'somewhat' support) on a 4 point Likert scale. CONCLUSION: Voters see active
      transportation infrastructure as being very important and support redirecting
      funding to improve the infrastructure. These findings can inform policy-decisions
      and planning efforts in the jurisdiction.

PMID- 25572623
TI  - Medical school curriculum characteristics associated with intentions and
      frequency of tobacco dependence treatment among 3rd year U.S. medical students.
AB  - OBJECTIVE: Physicians play a critical role in addressing tobacco dependence, yet
      report limited training. Tobacco dependence treatment curricula for medical
      students could improve performance in this area. This study identified student
      and medical school tobacco treatment curricula characteristics associated with
      intentions and use of the 5As for tobacco treatment among 3rd year U.S. medical
      students. METHODS: Third year medical students (N=1065, 49.3% male) from 10 U.S.
      medical schools completed a survey in 2009-2010 assessing student
      characteristics, including demographics, tobacco treatment knowledge, and self
      efficacy. Tobacco curricula characteristics assessed included amount and type of
      classroom instruction, frequency of tobacco treatment observation, instruction,
      and perception of preceptors as role models. RESULTS: Greater tobacco treatment
      knowledge, self-efficacy, and curriculum-specific variables were associated with
      5A intentions, while younger age, tobacco treatment self-efficacy, intentions,
      and each curriculum-specific variable were associated with greater 5A behaviors.
      When controlling for important student variables, greater frequency of receiving
      5A instruction (OR=1.07; 95%CI 1.01-1.12) and perception of preceptors as
      excellent role models in tobacco treatment (OR=1.35; 95%CI 1.04-1.75) were
      significant curriculum predictors of 5A intentions. Greater 5A instruction (B=.06
      (.03); p<.05) and observation of tobacco treatment (B=.35 (.02); p<.001) were
      significant curriculum predictors of greater 5A behaviors. CONCLUSIONS: Greater
      exposure to tobacco treatment teaching during medical school is associated with
      both greater intentions to use and practice tobacco 5As. Clerkship preceptors, or
      those physicians who provide training to medical students, may be particularly
      influential when they personally model and instruct students in tobacco
      dependence treatment.

PMID- 25572627
TI  - Unexpected migratory insertion reactions of M(alkyl)2 (M=Zn, Cd) and
      diamidocarbenes.
AB  - The electrophilic character of free diamidocarbenes (DACs) allows them to
      activate inert bonds in small molecules, such as NH3 and P4 . Herein, we report
      that metal coordinated DACs also exhibit electrophilic reactivity, undergoing
      attack by Zn and Cd dialkyl precursors to afford the migratory insertion products
      [(6-MesDAC-R)MR] (M=Zn, Cd; R=Et, Me; Mes=mesityl). These species were formed via
      the spectroscopically characterised intermediates [(6-MesDAC)MR2 ], exhibiting
      barriers to migratory insertion which increase in the order MR2 = ZnEt2 < ZnMe2 <
      CdMe2 . Compound [(6-MesDAC-Me)CdMe] showed limited stability, undergoing
      deposition of Cd metal, by an apparent beta-H elimination pathway. These results
      raise doubts about the suitability of diamidocarbenes as ligands in catalytic
      reactions involving metal species bearing nucleophilic ligands (M-R, M-H). 

PMID- 25572628
TI  - Community pharmacy patient perceptions of a pharmacy-initiated mobile technology
      app to improve adherence.
AB  - OBJECTIVES: To determine patient perceptions of using a demonstration application
      (app) of mobile technology to improve medication adherence and to identify
      desired features to assist in the management of medications. METHODS: A
      qualitative study using key informant interviews was conducted in a community
      pharmacy chain for patients aged 50 and older, on statin therapy and owning a
      smart device. KEY FINDINGS: Three main themes emerged from 24 interviews at four
      pharmacy locations, which included benefits, barriers and desired features of the
      app. Benefits such as accessibility, privacy, pros of appearance and
      beneficiaries were more likely to lead to usage of the app. Barriers that might
      prevent usage of the app were related to concerns of appearance, the burden it
      might cause for others, cost, privacy, motivation and reliability. Specific
      features patients desired were categorized under appearance, customization,
      communication, functionality, input and the app platform. CONCLUSIONS: Patients
      provided opinions about using a mobile app to improve medication adherence and
      assist with managing medications. Patients envisioned the app within their
      lifestyle and expressed important considerations, identifying benefits to using
      this technology and voicing relevant concerns. App developers can use patient
      perceptions to guide development of a mobile app addressing patient medication
      related needs.

PMID- 25572626
TI  - Assessment of bone synthetic activity in inflammatory lesions and syndesmophytes
      in patients with ankylosing spondylitis: the potential role of 18F-fluoride
      positron emission tomography-magnetic resonance imaging.
AB  - OBJECTIVES: 18F-fluoride uptake represents active osteoblastic bone synthesis. We
      assessed bone synthetic activity in inflammatory lesions and syndesmophytes in
      patients with ankylosing spondylitis (AS) using 18F-fluoride positron emission
      tomography-magnetic resonance imaging (PET-MRI, Philips Healthcare, Cleveland,
      OH, USA) and x-ray. METHODS: All images of 12 AS patients were recorded with the
      presence or absence of increased 18F-fluoride uptake lesions on PET, acute (type
      A) or advanced (type B) corner inflammatory lesions (CILs) on MRI, syndesmophytes
      on x-ray at the anterior vertebral corners. An increased 18F-fluoride uptake
      lesion was defined as an uptake which is greater than the uptake in the adjacent
      normal vertebral body. The association of a CIL or syndesmophyte with an
      increased 18F-fluoride uptake lesion was investigated by generalised linear
      latent mixed models analysis to adjust within-patient dependence for total
      numbers of vertebral corners. RESULTS: There were 67 type A CILs (12.1%), 37 type
      B CILs (6.7%) and 58 increased 18F-fluoride uptake lesion (10.4%) out of 552
      vertebral corners and there were 57 syndesmophytes (19.8%) out of 288 vertebral
      corners. A type A CIL (OR=3.2, 95% CI=1.6-6.5, p=0.001), type B CIL (OR=59.9, 95%
      CI=23.5-151.5, p<0.001) and syndesmpophyte (OR=21.8, 95% CI=5.5-85.2, p<0.001)
      were significantly associated with an increased 18F-fluoride uptake lesion.
      CONCLUSIONS: Our data suggest that an inflammatory lesion as well as a
      syndesmophyte is associated with active bone synthesis assessed by 18F-fluoride
      uptake in the spine of AS patients. 18F-fluoride PET-MRI may have the potential
      for investigating the pathogenesis of structural damage in AS.

PMID- 25572624
TI  - Recognizing disordered eating in primary care patients with obesity.
AB  - OBJECTIVE: In clinical practice, behavioral approaches to obesity treatment focus
      heavily on diet and exercise recommendations. However, these approaches may not
      be effective for patients with disordered eating behaviors. Little is known about
      the prevalence of disordered eating behaviors in primary care patients with
      obesity or whether they affect difficulty making dietary changes. METHODS: We
      conducted a telephone interview of 337 primary care patients aged 18-65 years
      with BMI >= 35 kg/m(2) in Greater Boston, 2009-2011 (58% response rate, 69%
      women). We administered the Three-Factor Eating Questionnaire R-18 (scores 0-100)
      and the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) (scores 0-100). We
      measured difficulty making dietary changes using four questions regarding
      perceived difficulty changing diet (Scores 0-10). RESULTS: 50% of the patients
      reported high emotional eating (score>50) and 28% reported high uncontrolled
      eating (score>50). Women were more likely to report emotional [OR=4.14 (2.90,
      5.92)] and uncontrolled eating [OR=2.11 (1.44, 3.08)] than men. African-Americans
      were less likely than Caucasians to report emotional [OR=0.29 (95% CI: 0.19,
      0.44)] and uncontrolled eating [OR=0.11 (0.07, 0.19)]. For every 10-point
      reduction in QOL score (IWQOL-lite), emotional and uncontrolled eating scores
      rose significantly by 7.82 and 5.48, respectively. Furthermore, participants who
      reported emotional and uncontrolled eating reported greater difficulty making
      dietary changes. SUMMARY: Disordered eating behaviors are prevalent among obese
      primary care patients and disproportionately affect women, Caucasians, and
      patients with poor QOL. These eating behaviors may impair patients' ability to
      make clinically recommended dietary changes. Clinicians should consider screening
      for disordered eating behaviors and tailoring obesity treatment accordingly.

PMID- 25572629
TI  - Orthology and paralogy constraints: satisfiability and consistency.
AB  - BACKGROUND: A variety of methods based on sequence similarity, reconciliation,
      synteny or functional characteristics, can be used to infer orthology and
      paralogy relations between genes of a given gene family  G. But is a given set  C
      of orthology/paralogy constraints possible, i.e., can they simultaneously co
      exist in an evolutionary history for  G? While previous studies have focused on
      full sets of constraints, here we consider the general case where  C does not
      necessarily involve a constraint for each pair of genes. The problem is
      subdivided in two parts: (1) Is  C satisfiable, i.e. can we find an event-labeled
      gene tree G inducing  C? (2) Is there such a G which is consistent, i.e., such
      that all displayed triplet phylogenies are included in a species tree? RESULTS:
      Previous results on the Graph sandwich problem can be used to answer to (1), and
      we provide polynomial-time algorithms for satisfiability and consistency with a
      given species tree. We also describe a new polynomial-time algorithm for the case
      of consistency with an unknown species tree and full knowledge of pairwise
      orthology/paralogy relationships, as well as a branch-and-bound algorithm in the
      case when unknown relations are present. We show that our algorithms can be used
      in combination with ProteinOrtho, a sequence similarity-based orthology detection
      tool, to extract a set of robust orthology/paralogy relationships.

PMID- 25572630
TI  - Modified-release calcifediol effectively controls secondary hyperparathyroidism
      associated with vitamin D insufficiency in chronic kidney disease.
AB  - BACKGROUND/AIMS: Vitamin D insufficiency drives secondary hyperparathyroidism
      (SHPT) and is associated with increased cardiovascular mortality in patients with
      chronic kidney disease (CKD). SHPT is poorly addressed by current vitamin D
      repletion options. The present study evaluated a novel investigational vitamin D
      repletion therapy: a modified-release (MR) formulation of calcifediol designed to
      raise serum 25-hydroxyvitamin D in a gradual manner to minimize the induction of
      CYP24 and, thereby, improve the SHPT control. METHODS: This randomized, double
      blind, placebo-controlled trial evaluated MR calcifediol in CKD subjects (n = 78)
      with plasma intact parathyroid hormone (iPTH) >70 pg/ml and serum total 25
      hydroxyvitamin D <30 ng/ml. Subjects received daily treatment for six weeks with
      oral MR calcifediol (30, 60 or 90 ug) or a placebo. RESULTS: More than 90% of
      subjects treated with MR calcifediol achieved serum 25-hydroxyvitamin D levels
      >=30 ng/ml versus 3% of subjects treated with placebo (p < 0.0001). Mean plasma
      iPTH decreased from baseline (140.3 pg/ml) by 20.9 +/- 6.2% (SE), 32.8 +/- 5.7
      and 39.3 +/- 4.3% in the 30, 60 and 90 ug dose groups, respectively, and
      increased 17.2 +/- 7.8% in the pooled placebo group (p < 0.005). No clinically
      significant safety concerns arose during MR calcifediol treatment. CONCLUSION:
      Oral MR calcifediol appears safe and highly effective in treating SHPT associated
      with vitamin D insufficiency in CKD.

PMID- 25572631
TI  - Trigeminal root compression for trigeminal neuralgia in patients with no vascular
      compression.
AB  - BACKGROUND: Trigeminal neuralgia (TN) may be present in the absence of vascular
      compressiom, and surgical treatment in these cases is controversial. Our
      objective is to evaluate the efficacy and safety of trigeminal root compression
      in this situation. METHODS: A prospective collection of clinical data on all
      patients diagnosed with idiopathic TN in our institution. Cases with no visible
      offending vessel intraoperatively were included in this study. These patients
      underwent trigeminal root compression and long-term follow-up. The basic
      characteristics and outcomes were analyzed. RESULTS: From February 2005 to
      November 2010, 381 patients underwent microvascular decompression for TN at our
      department. Among them, 28(7.3 %) patients (17 female, 11 male) had no visible
      vascular compression intraoperatively. The median observation period was 46
      months (range, 8-60 months). Twenty patients (71.4 %) achieved complete pain
      relief without medication immediately postoperatively. However, the recurrence
      rate was 38.4 %, and only 13 patients (46.4 %) achieved complete pain relief
      without medication at follow-up. Ten patients (35.7 %) developed some degree of
      facial numbness, which was transient in six cases (21.4 %) and permanent in four
      (14.3 %). CONCLUSIONS: Although trigeminal root compression provides good initial
      pain relief, the long-term efficacy, complication and recurrence rates are far
      from satisfactory. Further studies are needed to explore the possible mechanisms
      of underlying pain and to compare the outcomes of various types of interventions
      in cases without vascular compression.

PMID- 25572632
TI  - Endovascular management of adjacent tandem intracranial aneurysms: utilization of
      stent-assisted coiling and flow diversion.
AB  - BACKGROUND: Tandem intracranial aneurysms are aneurysms located along a single
      intracranial vessel. Adjacent tandem aneurysms arise within the same vascular
      segment and their presence often suggests diffuse parent vessel anomaly.
      Endovascular management of these rare lesions has not been well studied. In this
      retrospective observational study, we describe our experience treating adjacent
      tandem intracranial aneurysms with endovascular embolization. METHODS: We
      retrospectively reviewed records of patients with these lesions who underwent
      endovascular treatment between 2008 and 2013. RESULTS: Thirteen patients (mean
      age 60.8 years; 12 women) with 28 adjacent tandem aneurysms were treated during
      the study timeframe. Aneurysms were located along the clinoidal, ophthalmic, and
      communicating segments of the internal carotid artery in 12 patients and at the
      basilar apex in one patient. Average size was 8.4 mm. Six patients (12 aneurysms)
      were treated by flow diversion via the Pipeline embolization device (PED) and
      seven (16 aneurysms) by stent-assisted coiling, with coils successfully placed in
      11 aneurysms. Clinical follow-up was available for an average of 26.1 months;
      postprocedural angiography was performed for 12 patients. Complete occlusion was
      achieved in nine of ten (90 %) PED-treated aneurysms and eight of 11 (72.7 %)
      treated by stent-assisted coiling (p = 0.44). Two patients treated by stent
      assisted coiling required re-coiling for aneurysm recanalization. Overall,
      modified Rankin scale scores were 0-1 for 12 patients and 3 for one patient.
      CONCLUSIONS: Adjacent tandem intracranial aneurysms can be safely and effectively
      treated by either stent-assisted coiling or flow diversion. We prefer PED flow
      diversion due to better parent vessel reconstruction and lower recanalization
      risk.

PMID- 25572633
TI  - Microvascular decompression for typewriter tinnitus-case report.
AB  - BACKGROUND: Microvascular decompression has been tested as a treatment for
      tinnitus. METHODS: However, only a fraction of patients appear to benefit from
      surgery if the combination of findings such as paroxysmal vertigo, ABR changes
      and tinnitus is used to select patients for microvascular decompression. RESULTS:
      Instead, a more specific syndrome of staccato or "typewriter" tinnitus, which is
      highly responsive to carbamazepine, was suggested to be caused by a neurovascular
      conflict. CONCLUSION: We present the first case of typewriter tinnitus with
      complete long-term symptom relief following microvascular decompression of the
      vestibulocochlear nerve. We suggest that this specific syndrome is caused by a
      neurovascular conflict and treatable by microvascular decompression.

PMID- 25572634
TI  - Symmetry breaking and silver in gold nanorod growth.
AB  - Formation of anisotropic nanocrystals from isotropic single-crystal precursors
      requires an essential symmetry breaking event. Single-crystal gold nanorods have
      become the model system for investigating the synthesis of anisotropic
      nanoparticles, and their growth mechanism continues to be the subject of intense
      investigation. Despite this, very little is known about the symmetry breaking
      event that precedes shape anisotropy. In particular, there remains limited
      understanding of how an isotropic seed particle becomes asymmetric and of the
      growth parameters that trigger and drive this process. Here, we present direct
      atomic-scale observations of the nanocrystal structure at the embryonic stages of
      gold nanorod growth. The onset of asymmetry of the nascent crystals is observed
      to occur only for single-crystal particles that have reached diameters of 4-6 nm
      and only in the presence of silver ions. In this size range, small, asymmetric
      truncating surfaces with an open atomic structure become apparent. Furthermore,
      {111} twin planes are observed in some immature nanorods within 1-3 monolayers of
      the surface. These results provide direct observation of the structural changes
      that break the symmetry of isotropic nascent nanocrystals and ultimately enable
      the growth of asymmetric nanocrystals. 

PMID- 25572635
TI  - Next step toward the automation of screening for cervical cancer.

PMID- 25572636
TI  - The structural and compositional transition of the meniscal roots into the
      fibrocartilage of the menisci.
AB  - The meniscal roots, or insertional ligaments, firmly attach the menisci to tibial
      plateau. These strong attachments anchor the menisci and allow for the generation
      of hoop stress in the tissue. The meniscal roots have a ligament-like structure
      that transitions into the fibrocartilagenous structure of the meniscal body. The
      purpose of this study was to carry out a complete analysis of the structure and
      tissue organization from the body of the meniscus through the transition region
      and into the insertional roots. Serial sections were obtained from the meniscal
      roots into the meniscal body in fixed juvenile bovine menisci. Sections were
      stained for collagen and proteoglycans (PG) using fast green and safranin-o
      staining protocols. Unstained sections were imaged used a backlit stereo
      microscope. Optical projection tomography (OPT) was employed to evaluate the
      three-dimensional collagen architecture of the root-meniscus transition in lapine
      menisci. Tie-fibres were observed in the sections of the ligaments furthest from
      the bovine meniscal body. Blood vessels were observed to be surrounded by these
      tie-fibres and a PG-rich region within the ligaments. Near the tibial insertion,
      the roots contained large ligament-like collagen fascicles. In sections
      approaching the meniscus, there was an increase in tie-fibre size and density.
      Small tie-fibres extended into the ligament from the epiligamentous structure in
      the outermost sections of the meniscal roots, while large tie-fibre bundles were
      apparent at the meniscus transition. The staining pattern indicates that the root
      may continue into the outer portion of the meniscus where it then blends with the
      more fibrocartilage-like inner portions of the tissue. In unstained sections it
      was observed that the femoral side of the epiligamentous structure surrounding
      the root becomes more fibrous and thickens in the inferior inner portion of the
      posterior medial root. This thickening changes the shape of the root to more
      closely resemble the meniscus wedge shape. These observations support the concept
      of root continuity with the outer portion of the meniscus, thereby connecting
      with the hoop-like structure of the peripheral meniscus. OPT identified
      continuous collagen organization from the root into the meniscal body in
      longitudinal sections. In the radial direction, the morphology of the root
      continues into the meniscal body consistent with the serially sectioned bovine
      menisci. Blood vessels were prevalent on the periphery of the root. These blood
      vessels then arborized to cover the anterior femoral surface of the meniscus.
      This is the first study of the structural transition between the insertional
      ligaments (roots) and the fibrocartilagenous body of the menisci. These new
      structural details are important to understanding the meniscal load-bearing
      mechanism in the knee. 

PMID- 25572637
TI  - Is infertility really associated with higher levels of mental distress in the
      female population? Results from the North-Trondelag Health Study and the Medical
      Birth Registry of Norway.
AB  - OBJECTIVE: To explore the effect of ever having tried to conceive for more than
      12 months on levels of anxiety and depressive symptoms and to investigate if
      symptom levels of anxiety and depression in infertile women who remain childless,
      or go on to have children, respectively, differ from symptom levels in mothers
      without reports of infertility. METHODS: Analyses were based on information from
      12 584 Norwegian women aged 19-45 years who participated in the North-Trondelag
      Health Study from 1995 to 1997 and data from the Medical Birth Registry of
      Norway. Anxiety and depressive symptoms were measured by the Hospital Anxiety and
      Depression Scale. RESULTS: Having tried to conceive for more than 12 months
      (ever) was weakly associated with higher levels of depressive symptoms. In the
      categorical analyses, women with resolved infertility had higher levels of
      anxiety symptoms (B = 0.25 (95% confidence interval (CI) = 0.04-0.47)) and
      voluntarily childfree had lower levels of depressive symptoms (B = -0.05 (95% CI
      = -0.50 to -0.21)) than mothers without infertility. However, women with current
      primary or current secondary infertility had levels of anxiety and depression not
      significantly different from mothers without infertility. CONCLUSION: At the
      population level, and from a longitudinal perspective, unresolved infertility is
      less burdensome than findings from studies on women seeking help for infertility
      would suggest.

PMID- 25572639
TI  - Precious-metal-free Co-Fe-O/rGO synergetic electrocatalysts for oxygen evolution
      reaction by a facile hydrothermal route.
AB  - Abundant iron group metal oxides and their composites possess great potential in
      the application of electrochemical energy storage and conversion. In this work,
      we obtained Co-Fe-O composites/reduced graphene oxides (CFO/rGO) hybrid
      structures, engineered their compositions, phase, and structures by a facile
      hydrothermal route, and studied their composition-dependent activity for
      electrochemical oxygen evolution reaction (OER) in alkaline media. It is found
      that synergetic effects bring a clear decrease in overpotential and Tafel slope
      for CFO/rGO catalysts in comparison with monometallic composition/rGO catalysts.
      OER charge-transfer resistance is significantly reduced after Fe addition,
      indicating that the reaction barriers of CFO/rGO are reduced. The optimal CFO/rGO
      with Co-Fe ratio of 2:1 was identified. Our results on the synergetic effects of
      CFO/rGO enrich the understanding of iron-group composites for electrocatalytic
      applications. 

PMID- 25572638
TI  - Human papillomavirus serology and tobacco smoking in a community control group.
AB  - BACKGROUND: HPV infection is an established risk factor for oropharyngeal cancer,
      and it has been proposed that cigarette smoking may potentiate HPV infection in
      the oral epithelium. We sought to test the hypothesis that cigarette smoking
      increases HPV infection in an HPV16 serology study of cancer-free individuals.
      METHODS: Subjects were participants in a risk factor study for head and neck
      cancer, and were required to have no prior history of either HNSCC or any other
      cancer. Tobacco use and other risk factor data were gathered through interviewer
      assisted questionnaires, while serology was conducted in a blinded fashion using
      a glutathione S-transferase capture enzyme-linked immunosorbent assay (ELISA) to
      detect antibodies against HPV16 L1, E1, E2, E4, E6 and E7 proteins. The
      differences in tobacco use by HPV serology were evaluated by ANOVA; and the
      reported odds ratios and 95% confidence intervals were determined by using
      unconditional logistic regression. RESULTS: We found no overall association of
      HPV16 serological markers with smoking. However, when the data were stratified by
      median age, smoking was positively associated with seropositivity for the HPV16
      L1 capsid antigen in the younger controls while the older controls were less
      likely to be HPV16 L1 positive if they smoked (pinteraction < 0.002). There was
      no similar association of smoking and age with serological response to the early
      proteins (i.e E6, E7). CONCLUSIONS: Exposure to HPV16 capsid protein (L1) is
      increased among relatively younger adults who smoke and diminished among older
      smokers. However, this pattern is not accompanied by a differential
      susceptibility for active infection (as determined by the early gene proteins
      such as E6 and E7) among young and older smokers.

PMID- 25572640
TI  - Creating ED point-of-care testing protocols: an expert panel and Delphi process.

PMID- 25572641
TI  - Prehospital pain management of injured children: a systematic review of current
      evidence.
AB  - OBJECTIVES: Injury is a common cause of acute pain in children. The objective of
      this study was to analyze the available evidence in prehospital pain management
      of injured children. METHODS: The Patient/Population, Intervention, Comparator,
      and Outcome question was as follows: "In pediatric patients requiring prehospital
      analgesia for traumatic injuries, what is the level of evidence (LOE) available
      for the safety and efficacy of pharmacologic interventions?" The electronic
      databases MEDLINE/PUBMED, EMBASE, and Google Scholar were searched to identify
      all the relevant articles published in electronic journals, books, and scientific
      Web sites over the last 20 years. Studies were included if they reported on
      prehospital use of analgesics in injured children. Reviews, editorials, and
      surveys were excluded. RESULTS: Nineteen studies met the inclusion criteria.
      Thirteen were pediatric studies and 6 were studies of both adults and children.
      Nine were nonrandomized studies with concurrent controls (LOE-2), and 10 were
      retrospective case series and chart reviews (LOE-4). A measurable effect of
      analgesia was consistently found when analgesics were provided en route to the
      hospital; however, most studies reported a relatively low rate of analgesic use.
      CONCLUSIONS: Only a few studies examined the efficacy of pediatric prehospital
      analgesia. Fentanyl at a dose of 1 to 3 MUg/mg seems to have an accepted
      efficacy. The current level of evidence is insufficient to assess the safety
      profile of analgesics. The findings of this study suggest that the analgesic
      treatment of injured children in the prehospital setting is suboptimal.

PMID- 25572642
TI  - Acute iterative bronchospasm and "do not re-intubate" orders: sedation by an
      alpha-2 agonist combined with noninvasive ventilation.
AB  - A male patient presented with bronchospasm and acute respiratory distress. The
      patient had presented 2 previous episodes of severe bronchospasm following
      abdominal surgery, leading twice to intubation, mechanical ventilation, and
      conventional sedation. As the patient positively rejected a third episode of
      intubation + mechanical ventilation, noninvasive ventilation (pressure support =
      8 cm H2O, positive end-expiratory pressure = 10 cm H2O), inhaled therapy, and
      clonidine orally (~ 4 MUg/kg) were combined. Over 1 to 2 hours, the acute
      respiratory distress disappeared. Noninvasive ventilation was discontinued on the
      next morning (day 2). The patient was discharged from the critical care unit on
      day 3 on good condition but died at a later interval from iterative bronchospasm.
      Evidence-based documentation of the effects of alpha-2 agonists in the setting of
      acute bronchospasm in the emergency department or status asthmaticus in the
      critical care unit is awaited.

PMID- 25572643
TI  - Diagnostic performance of cardiopulmonary ultrasound performed by the emergency
      physician in the management of acute dyspnea.
AB  - OBJECTIVE: The etiologic diagnosis of acute dyspnea in the emergency department
      (ED) remains difficult, especially for elderly patients or those with previous
      cardiorespiratory medical history. This may lead to inappropriate treatment and
      potentially a higher mortality rate. Our objective was to evaluate the
      performance of cardiopulmonary ultrasound compared with usual care for the
      etiologic diagnosis of acute dyspnea in the ED. METHODS: Patients admitted to the
      ED for acute dyspnea underwent upon arrival a cardiopulmonary ultrasound
      performed by an emergency physician, in addition to standard care. The
      performances of the clinical examination, chest x-ray, N-terminal brain
      natriuretic peptide (NT-proBNP), and cardiopulmonary ultrasound were compared
      with the final diagnosis made by 2 independent physicians. RESULTS: One hundred
      thirty patients were analyzed. For the diagnosis of acute left-sided heart
      failure, cardiopulmonary ultrasound had an accuracy of 90% (95% confidence
      interval [CI], 84-95) vs 67% (95% CI, 57-75), P = .0001 for clinical examination,
      and 81% (95% CI, 72-88), P = .04 for the combination "clinical examination-NT
      proBNP-x-ray". Cardiopulmonary ultrasound led to the diagnosis of pneumonia or
      pleural effusion with an accuracy of 86% (95% CI, 80-92) and decompensated
      chronic obstructive pulmonary disease or asthma with an accuracy of 95% (95% CI,
      92-99). Cardiopulmonary ultrasound lasted an average of 12 +/- 3 minutes.
      CONCLUSIONS: Cardiopulmonary ultrasounds performed in the ED setting allow one to
      rapidly establish the etiology of acute dyspnea with an accuracy of 90%.

PMID- 25572644
TI  - Impact of clinical decision support on head computed tomography use in patients
      with mild traumatic brain injury in the ED.
AB  - BACKGROUND: Reduction of unnecessary head computed tomographies (CTs) in patients
      with mild traumatic brain injury (MTBI) was recently endorsed by American College
      of Emergency Physicians (ACEP) in the "Choosing Wisely" campaign. We examined the
      impact of computerized clinical decision support (CDS) on head CT utilization in
      MTBI emergency department (ED) visits. METHODS: We conducted a 2-year cohort
      study at a level 1 trauma center and compared our results with the National
      Hospital Ambulatory Medical Care Survey from 2009 to 2010. All adult patients
      discharged from the ED with MTBI-associated diagnoses were included. After a
      baseline observation period at our institution, real-time CDS was implemented.
      Based upon the clinical history entered, low utility orders triggered an alert to
      clinicians, suggesting imaging studies might not adhere to evidence-based
      guidelines. Clinicians could cancel the order or ignore the alert. Primary
      outcome was intensity of head CT use in MTBI ED visits. Secondary outcomes
      included rates of delayed imaging and delays in diagnosing radiologically
      significant findings. chi(2), logistic regression, and process control chart
      assessed preintervention and postintervention differences. RESULTS: In study
      patients, 58.1% of MTBI-related visits resulted in head CT preintervention vs
      50.3% postintervention (13.4% relative decrease, P = .005), a change not detected
      in controls (73.3% vs 76.9%, P = .272). Study cohort patients not receiving a
      head CT during their index visit were neither more nor less likely to receive one
      in the subsequent 7 days (6.7% preintervention vs 9.4% postintervention, P =
      .231). Rates of delayed diagnosis of radiologically significant findings were
      unchanged (0% vs 0%). CONCLUSIONS: Evidence-based CDS can reduce low utility
      imaging for MTBI.

PMID- 25572645
TI  - Emergency neurosurgical care in patients treated with apixaban: report of 2
      cases.
AB  - A debate has emerged regarding the safety profile of direct anticoagulants, which
      are increasingly prescribed for the prevention of thromboembolic events. Despite
      favorable safety data derived from controlled clinical trials, the absence of
      specific antidotes for the management of hemorrhagic complications represents a
      major challenge for emergency physicians. Here, we present the first report on
      patients treated with the direct factor Xa inhibitor apixaban and conditions
      requiring urgent neurosurgical intervention (intracerebral hemorrhage, n = 1;
      subdural hematoma, n = 1). Prothrombin complex concentrates were administered
      before surgery, and both patients had a favorable postsurgical course without
      bleeding or thromboembolic complications. Further studies are needed, but this
      approach seems to be suitable for the emergency management of apixaban-associated
      intracranial hemorrhage.

PMID- 25572646
TI  - A patient with refractory shock induced by several factors, including obstruction
      because of a posterior mediastinal hematoma.
AB  - A 44-year-old man who drove a motorcycle experienced a collision with the side of
      another motorcycle. Because he had sustained a high-energy injury to the spinal
      cord, he was transferred to our hospital. His circulation was unstable, and
      received tracheal intubation in addition to thoracostomy for the hemothorax.
      Whole-body computed tomography (CT) revealed multiple fractures, right
      hemopneumothorax with pulmonary contusion, and minor liver injury. After infusing
      5000 mL of lactated Ringer's solution and 10 units of blood, his circulation
      remained unstable. On a repeat CT examination, the left atrium was found to be
      compressed by a posterior mediastinal hematoma induced by the fracture of the
      thoracic spine, and a diagnosis of shock induced by multiple factors, including
      hemorrhagic, neurogenic, and obstructive mechanisms, was made. After obtaining
      stable circulation and respirations, internal fixation of the extremities and
      extubation were performed on the 12th hospital day. Chest CT performed on the
      27th day showed the disappearance of compression of the left atrium by the
      hematoma.

PMID- 25572647
TI  - Neurogenic pulmonary edema after severe head injury: a transpulmonary
      thermodilution study.
AB  - Neurogenic pulmonary edema (NPE) is a possible complication of severe central
      nervous system insult. Its physiopathology is still debated. We report a fatal
      case of a 55-year-old man who was admitted because of severe head injury. The
      diagnosis of NPE was considered according to clinical and radiologic findings.
      Transpulmonary thermodilution study showed decreased stroke volume index and
      cardiac function index. Indexed extravascular lung water was increased as well as
      pulmonary vascular permeability index. The impairment of the left ventricular
      function was confirmed by the echocardiographic study. Our case suggests that NPE
      imply both cardiac dysfunction and lung injury. Thus, transpulmonary
      thermodilution can be helpful in managing fluid balance and the choice of
      vasopressors in patients with life-threatening NPE.

PMID- 25572648
TI  - Population estimate of the preantral follicles and frequency of multioocyte
      follicles in prepubertal and adult bitches.
AB  - Oocytes from preantral follicles could be an alternative for in vitro maturation
      because most follicles are at the preantral stage. There are few studies that
      have sought to estimate the number of preantral follicles in bitches. Therefore,
      the aims of this study were to estimate the population of preantral follicles in
      the ovaries of small- and medium-sized prepubertal and adult bitches and compare
      the population of preantral follicles between the right and left ovaries and
      evaluate the frequency of multioocyte follicles (MOF). Eighty ovaries were
      collected by elective ovariohysterectomy from 40 healthy bitches. The bitches
      were divided into four groups: small-size prepubertal bitches (<10 kg, n = 20),
      medium-size prepubertal bitches (10-20 kg, n = 20), small-size adult bitches (<10
      kg, n = 20), and medium-size adult bitches (10-20 kg, n = 20). Immediately after
      surgery, the ovaries were fixed in Bouin's solution and processed for histology.
      For each specimen, 70 histologic sections were cut and mounted on slides; then,
      the number of preantral follicles was estimated using a correction factor. The
      preantral follicles were classified according to the developmental stage. The
      data were analyzed using the Kruskal-Wallis test followed by Dunn's test for
      comparison between groups, and Fisher's exact test was used to evaluate the
      frequency of MOF (P <= 0.05). Considering the population of preantral follicles
      from the pair of ovaries, medium-size prepubertal bitches had the highest (P <
      0.05) population of preantral follicles compared with the small and medium-size
      adult groups. There was a large variation in the numbers of preantral follicles
      among individuals of the same weight and within each group. There were
      differences between medium-size prepubertal and adult bitches regarding the
      population of preantral follicles in the right ovaries (145,482 +/- 110,712 vs.
      49,500 +/- 44,821; P = 0.02); however, no differences were observed between the
      groups on the basis of comparisons of the number of preantral follicles in the
      left ovaries (P > 0.05). The prevalence of primordial MOF was higher in
      prepubertal bitches (47% vs. 28%), whereas adult bitches had a higher frequency
      of secondary MOF (49% vs. 25%; P < 0.05). We conclude that medium-size
      prepubertal bitches had the highest population of preantral follicles compared
      with small and medium-size adult bitches, and the use of only one ovary per bitch
      implied contrasting result. The presence of primordial MOF was higher in
      prepubertal bitches and at the secondary stage in adult bitches. 

PMID- 25572649
TI  - Evaluation of intracellular pH regulation and alkalosis defense mechanisms in
      preimplantation embryos.
AB  - Intracellular pH (pHi) regulation is an important homeostatic function of cells.
      There are three major pHi-regulatory mechanisms: HCO3(-)/Cl(-) exchanger (anion
      exchanger [AE]), which alleviates alkalosis, and the Na(+)/H(+) and Na(+),HCO3(
      )/Cl(-) exchangers, both of which alleviate acidosis. We hypothesized that there
      would be developmental changes in pHi-regulatory activity in preimplantation
      embryos as conditions in the oviduct are alkaline but acidic in the uterus. This
      study focused on the AE mechanism in pronuclear (PN) zygotes, two-cell (2-c),
      four-cell (4-c), morula, and blastocyst stage embryos from Balb/c mice.
      Microspectrofluorometry was used to monitor changes in pHi in embryos subjected
      to Cl(-)-free media in presence or absence of an AE inhibitor, DIDS, and in
      embryos recovering from NH4Cl-induced alkalosis. Real-time polymerase chain
      reaction was used to identify AE isoforms. The pHi changes were greatest in PN
      zygotes (0.086 +/- 007 pHU/min) but fell as embryos developed to the 2-c, 4-c,
      morula, and blastocyst stages (0.063 +/- 006; 0.035 +/- 007; 0.024 +/- 004, and
      0.014 +/- 004 pHU/min, respectively). DIDS significantly reduced the rise in pHi
      caused by Cl(-) removal in all embryos; the finding pointed out that this pHi
      changes are due to AE activity. But DIDS only inhibited the recovery responses of
      PN zygote, 2-c and 4-c embryos but not morula or blastocyst stage embryos. In
      bicarbonate-containing medium, all embryos recovered from induced alkalosis but
      only the morula and blastocyst stages could fully compensate from ammonium
      induced-alkalosis in bicarbonate-free medium. The finding showed that commonly
      used ammonium pulse method to investigate AE function against alkalosis is not
      suitable for morula and blastocyst embryonic stages. All embryos expressed SLC4A2
      and SLC4A4 coding for AE-2 and AE-4, but none expressed either AE-1 or AE-3. The
      gradual change in the response to alkalosis in preimplantation embryos may be
      adaptations to their normal in vivo environment, where the early embryos are
      located in the alkaline oviduct, whereas the morula and blastocyst move into the
      acidic uterus. 

PMID- 25572650
TI  - The first 2(IB),3(IA)-heterodifunctionalized beta-cyclodextrin derivatives as
      artificial enzymes.
AB  - Novel 2,3-heterodisubstituted beta-cyclodextrin derivatives were designed as
      artificial enzymes to degrade chemical warfare agents. One of them reduced the
      acetylcholinesterase inhibitory potential by soman faster than its
      monosubstituted analog. 

PMID- 25572651
TI  - BPA-induced DNA hypermethylation of the master mitochondrial gene PGC-1alpha
      contributes to cardiomyopathy in male rats.
AB  - Implication of environmental endocrine disruptors, such as bisphenol A (BPA), on
      the development of cardiopathy has been poorly investigated. The aim of the study
      was to investigate the effects of long-term exposure to BPA at the reference dose
      on the myocardium of rats, and the underlying mechanisms. Male rats received corn
      oil or 50 MUg/kg/day of BPA since delactation. At 24 and 48 weeks (wk), cardiac
      function and mitochondrial function were examined. The mRNA expression and the
      methylation status of PCG-1alpha, a major regulator of mitochondrial biogenesis
      in cardiac muscle, were also tested. At 48 wk, BPA-exposed rats displayed
      cardiomyopathy, characterized by myocardium hypertrophy, cardiomyocyte
      enlargement, and impairment of cardiac function. At 24 wk, significantly reduced
      ATP production, dissipated mitochondrial membrane potential (Psim) and declined
      mitochondrial respiratory complex (MRC) activity in cardiomyocytes were observed
      in BPA-exposed rats compared with the control rats, indicating a decrease in
      mitochondrial function occurs before the development of cardiomyopathy.
      Additionally, BPA exposure decreased the expression of PGC-1alpha and induced
      hypermethylation of PGC-1 alpha in heart tissue in 24- and 48-week-old rats. The
      change in methylation of PGC-1alpha was observed more pronounced in BPA-exposed
      rats at 48 wk. Overall, long-term BPA exposure induces cardiomyopathy in male
      rats, and the underlying mechanism may involve the impairment of cardiac
      mitochondrial function and the disturbance of methylation of PGC-1alpha.

PMID- 25572652
TI  - Potential for acceleration of bone formation after implant surgery by using a
      dietary supplement: an animal study.
AB  - Dental implant treatment is an effective modality to restore lost aesthetic and
      masticatory functions. However, healing after implant surgery takes at least 3-6
      months. This prolonged healing period poses several difficulties for individuals
      with a large edentulous area and decreases their quality of life. Consequently,
      shortening the healing period and accelerating final prosthesis placement after
      surgery is very clinically important. Peri-implant bone formation may be enhanced
      by systemic approaches, such as the use of osteoporosis supplements, to promote
      bone metabolism. To confirm whether intake of a supplement developed for
      osteoporosis, synthetic bone mineral (SBM), was effective in accelerating peri
      implant bone formation as part of the healing process after implantation. Twenty
      four 5-week-old female Wistar rats were randomly assigned to receive a
      standardised diet without (control group, n = 12) or with SBM (n = 12). The rats
      had implant surgery at 8 weeks of age under general anaesthesia. The main outcome
      measures were bone mineral density (BMD) and pull-out strength in the implant and
      femur, which were compared between the groups at 2 and 4 weeks after implantation
      using the Mann-Whitney U test. BMD was significantly greater in the SBM group at
      2 and 4 weeks after implantation compared to the control group. Pull-out strength
      was significantly greater in the SBM groups at 2 and 4 weeks after implantation
      compared to the control group. This study demonstrated that SBM could be
      effective in accelerating peri-implant bone formation during the healing period
      after implantation.

PMID- 25572653
TI  - Cerebral oxygenation and processed EEG response to clamping and shunting during
      carotid endarterectomy under general anesthesia.
AB  - Clamping and shunting during carotid endarterectomy (CEA) surgery causes changes
      in cerebral blood flow. The purpose of this study was to assess and compare, side
      by side, the cerebral oxygenation (rSO2) and processed electroencephalogram (EEG)
      response bilaterally to carotid artery clamping and shunting in patients
      undergoing CEA under general anesthesia. With institutional approval and written
      informed consent, patients undergoing CEA under general anesthesia and routine
      carotid artery shunting were recorded bilaterally, simultaneously and
      continuously with an rSO2 and processed EEG monitor. The response of the monitors
      during carotid artery clamping and shunting were assessed and compared between
      monitors and bilaterally within each monitor. Sixty-nine patients were included
      in the study. At clamping the surgical-side and contralateral-side rSO2 dropped
      significantly below the baseline incision value (-17.6 and -9.4% respectively).
      After shunting, the contralateral-side rSO2 returned to baseline while the
      surgical-side rSO2 remained significantly below baseline (-9.0%) until the shunt
      was removed following surgery. At clamping the surgical-side and contralateral
      side processed EEG also dropped below baseline (-19.9 and -20.6% respectively).
      However, following shunt activation, the processed EEG returned bilaterally to
      baseline. During the course of this research, we found the rSO2 monitor to be
      clinically more robust (4.4% failure rate) than the processed EEG monitor (20.0%
      failure rate). There was no correlation between the rSO2 or processed EEG changes
      that occurred immediately after clamping and the degree of surgical side stenosis
      measured pre-operatively. Both rSO2 and processed EEG respond to clamping and
      shunting during CEA. Cerebral oximetry discriminates between the surgical and
      contralateral side during surgery. The rSO2 monitor is more reliable in the real
      world clinical setting. Future studies should focus on developing algorithms
      based on these monitors that can predict clamping-induced cerebral ischemia
      during CEA in order to decide whether carotid artery shunting is worth the
      associated risks. From the practical point of view, the rSO2 monitor may be the
      better monitor for this purpose.

PMID- 25572655
TI  - Successful Elimination of Methotrexate by Continuous Veno-venous Haemofiltration
      in a Psoriatic Patient with Methotrexate Intoxication.

PMID- 25572654
TI  - Do eating disorders in parents predict eating disorders in children? Evidence
      from a Swedish cohort.
AB  - OBJECTIVE: We investigated whether parental eating disorders (ED) predict ED in
      children, using a large multigeneration register-based sample. METHOD: We used a
      subset of the Stockholm Youth Cohort born 1984-1995 and resident in Stockholm
      County in 2001-2007 (N = 286,232), The exposure was a diagnosed eating disorder
      in a parent; the outcome was any eating disorder diagnosis in their offspring,
      given by a specialist clinician, or inferred from an appointment at a specialist
      eating disorder clinic. A final study sample of 158,697 (55.4%) had data on these
      variables and confounding factors and contributed a total of 886,241 person years
      to the analysis. RESULTS: We found good evidence in support of the hypothesis
      that ED in either parent are independently associated with ED in their female
      children (HR 1.97 (95% CI: 1.17-3.33), P = 0.01) and that ED in mothers are
      independently associated with ED in their female children (HR 2.35 (95% CI: 1.39
      3.97) P = 0.001). Numbers were too low to permit separate analysis of ED in
      parents and their male children. CONCLUSION: Eating disorders in parents were
      associated with ED in children. This study adds to our knowledge about the
      intergenerational transmission of ED, which will help identify high-risk groups
      and brings about the possibility of targeted prevention.

PMID- 25572656
TI  - Simultaneous Estimation of Withaferin A and Z-Guggulsterone in Marketed
      Formulation by RP-HPLC.
AB  - A simple, rapid, precise and accurate high-performance liquid chromatography
      (HPLC) method was developed for simultaneous estimation of withaferin A and Z
      guggulsterone in a polyherbal formulation containing Withania somnifera and
      Commiphora wightii. The chromatographic separation was achieved on a Purosphere
      RP-18 column (particle size 5 um) with a mobile phase consisting of Solvent A
      (acetonitrile) and Solvent B (water) with the following gradients: 0-7 min, 50% A
      in B; 7-9 min, 50-80% A in B; 9-20 min, 80% A in B at a flow rate of 1 mL/min and
      detection at 235 nm. The marker compounds were well separated on the chromatogram
      within 20 min. The results obtained indicate accuracy and reliability of the
      developed simultaneous HPLC method for the quantification of withaferin A and Z
      guggulsterone. The proposed method was found to be reproducible, specific,
      precise and accurate for simultaneous estimation of these marker compounds in a
      combined dosage form. The HPLC method was appropriate and the two markers are
      well resolved, enabling efficient quantitative analysis of withaferin A and Z
      guggulsterone. The method can be successively used for quantitative analysis of
      these two marker constituents in combination of marketed polyherbal formulation. 

PMID- 25572657
TI  - Epstein-Barr virus-associated smooth muscle tumors in children following solid
      organ transplantation: a review.
AB  - EBV-SMT are a rare entity following organ transplantation. Given the rarity of
      the tumor, there is no standard approach to diagnosis and treatment. A literature
      search identified 28 reported cases of EBV-SMT in addition to our own experience
      with one case. The aim of this review is to summarize the existing data regarding
      pathogenesis, diagnosis, and treatment. 

PMID- 25572658
TI  - The toxicity and distribution of iron oxide-zinc oxide core-shell nanoparticles
      in C57BL/6 mice after repeated subcutaneous administration.
AB  - Therapeutic cancer vaccines promote immune responses by delivering tumour
      specific antigens. Recently, we developed iron oxide (Fe3 O4 )-zinc oxide (ZnO)
      core-shell nanoparticles (CSNPs) as carriers for antigen delivery into dendritic
      cells (DCs), and the CSNPs were injected subcutaneously into C57BL/6 mice to
      examine the systemic toxicity, tissue distribution and excretion of the CSNPs.
      The doses injected were 0, 4, 20 and 200 mg kg(-1) weekly for 4 weeks. No
      significant changes were observed after the CSNPs administration with respect to
      mortality, clinical observations, body weight, food intake, water consumption,
      urinalysis, haematology, serum biochemistry,and organ weights. A dose-dependent
      increase in granulomatous inflammation was observed at the injection site of the
      CSNP-treated animals, but no other histopathological lesions in other organs
      could be attributed to the CSNPs. The Zn concentration, which is an indicator for
      CSNPs, was not significantly higher in the sampled tissues, urine, or faeces
      after the CSNP injection. In contrast, the Zn concentration at the subcutaneous
      skin of the site injected with the CSNPs increased in a dose-dependent manner,
      along with a macroscopic deposition of the CSNPs. The CSNP residue at the
      injection site resulted in a foreign body response with the appearance of
      macrophage infiltration, but otherwise did not show any systemic distribution or
      toxicity at up to 200 mg kg(-1) during this study. In conclusion, CSNPs could be
      used as good antigen carriers for DC-based immunotherapy, although further study
      is needed to completely clear the residue of the CSNPs at the injection site.

PMID- 25572659
TI  - Real-time GIS data model and sensor web service platform for environmental data
      management.
AB  - BACKGROUND: Effective environmental data management is meaningful for human
      health. In the past, environmental data management involved developing a specific
      environmental data management system, but this method often lacks real-time data
      retrieving and sharing/interoperating capability. With the development of
      information technology, a Geospatial Service Web method is proposed that can be
      employed for environmental data management. The purpose of this study is to
      determine a method to realize environmental data management under the Geospatial
      Service Web framework. METHODS: A real-time GIS (Geographic Information System)
      data model and a Sensor Web service platform to realize environmental data
      management under the Geospatial Service Web framework are proposed in this study.
      The real-time GIS data model manages real-time data. The Sensor Web service
      platform is applied to support the realization of the real-time GIS data model
      based on the Sensor Web technologies. RESULTS: To support the realization of the
      proposed real-time GIS data model, a Sensor Web service platform is implemented.
      Real-time environmental data, such as meteorological data, air quality data, soil
      moisture data, soil temperature data, and landslide data, are managed in the
      Sensor Web service platform. In addition, two use cases of real-time air quality
      monitoring and real-time soil moisture monitoring based on the real-time GIS data
      model in the Sensor Web service platform are realized and demonstrated. The total
      time efficiency of the two experiments is 3.7 s and 9.2 s. CONCLUSIONS: The
      experimental results show that the method integrating real-time GIS data model
      and Sensor Web Service Platform is an effective way to manage environmental data
      under the Geospatial Service Web framework.

PMID- 25572660
TI  - Protective effect of erythropoietin against myocardial injury in rats with sepsis
      and its underlying mechanisms.
AB  - The aim of this study was to investigate the protective effect of erythropoietin
      (EPO) against acute myocardial injury and its underlying mechanisms. Mice (n=146)
      were randomly divided in a double-blind manner into four groups, sham, Rocephin,
      EPO and sepsis, and mortality was observed on the seventh day after cecal
      ligation and puncture. In addition, a total of 252 rats were randomly divided
      into three groups, sham, EPO and sepsis, and indicators of cardiac function,
      inflammatory mediators and serum creatine kinase levels were assessed.
      Mitochondrial membrane potential, cell apoptosis and nuclear factor kappa-light
      chain-enhancer of activated B cells (NF-kappaB) p65 expression levels were
      detected using flow cytometry. Following intervention with EPO, the mortality
      rate in mice with sepsis was significantly reduced and the cardiac function of
      septic rats was significantly improved. In addition, the levels of inflammatory
      mediators, serum creatine kinase and apoptosis and the myocardial mitochondrial
      membrane potential and expression of NF-kappaB p65 in cardiac tissue were all
      improved following EPO treatment, and the differences between the results for the
      sepsis and EPO groups were statistically significant (P<0.05). These findings
      suggest that EPO reduces the myocardial inflammatory response in septic rats,
      attenuates the reduction in mitochondrial membrane potential and inhibits
      myocardial cell apoptosis by reducing NF-kappaB p65 expression, and therefore
      exerts a protective effect in the myocardium.

PMID- 25572661
TI  - A highly efficient approach to protein interactome mapping based on collaborative
      filtering framework.
AB  - The comprehensive mapping of protein-protein interactions (PPIs) is highly
      desired for one to gain deep insights into both fundamental cell biology
      processes and the pathology of diseases. Finely-set small-scale experiments are
      not only very expensive but also inefficient to identify numerous interactomes
      despite their high accuracy. High-throughput screening techniques enable
      efficient identification of PPIs; yet the desire to further extract useful
      knowledge from these data leads to the problem of binary interactome mapping.
      Network topology-based approaches prove to be highly efficient in addressing this
      problem; however, their performance deteriorates significantly on sparse putative
      PPI networks. Motivated by the success of collaborative filtering (CF)-based
      approaches to the problem of personalized-recommendation on large, sparse rating
      matrices, this work aims at implementing a highly efficient CF-based approach to
      binary interactome mapping. To achieve this, we first propose a CF framework for
      it. Under this framework, we model the given data into an interactome weight
      matrix, where the feature-vectors of involved proteins are extracted. With them,
      we design the rescaled cosine coefficient to model the inter-neighborhood
      similarity among involved proteins, for taking the mapping process. Experimental
      results on three large, sparse datasets demonstrate that the proposed approach
      outperforms several sophisticated topology-based approaches significantly. 

PMID- 25572663
TI  - Novel splice-site mutation in SMN1 associated with a very severe SMA-I phenotype.
AB  - Spinal muscular atrophy (SMA) is a genetic disorder characterized by degeneration
      of motor neurons and muscle weakness and atrophy. The majority of patients harbor
      homozygous SMN1 deletions, resulting in an SMN1-null genotype. A variable number
      of copies of SMN2, the centromeric copy of SMN1, fails to compensate for the
      absence of SMN1 but can act as a modifier. Less than 5% of patients with SMA
      display intragenic mutations on the second allele, detectable by direct
      sequencing. The effects of these mutations are not easily predictable, hindering
      a clear correlation with the clinical phenotype. We describe a novel SMN1
      mutation that affected the donor splice site of exon 7 and resulted in an
      unusually severe SMA phenotype with rapid fatal outcome in an Italian infant.

PMID- 25572664
TI  - Novel silica surface charge density mediated control of the optical properties of
      embedded optically active materials and its application for fiber optic pH
      sensing at elevated temperatures.
AB  - Silica and silica incorporated nanocomposite materials have been extensively
      studied for a wide range of applications. Here we demonstrate an intriguing
      optical effect of silica that, depending on the solution pH, amplifies or
      attenuates the optical absorption of a variety of embedded optically active
      materials with very distinct properties, such as plasmonic Au nanoparticles, non
      plasmonic Pt nanoparticles, and the organic dye rhodamine B (not a pH indicator),
      coated on an optical fiber. Interestingly, the observed optical response to
      varying pH appears to follow the surface charge density of the silica matrix for
      all the three different optically active materials. To the best of our knowledge,
      this optical effect has not been previously reported and it appears universal in
      that it is likely that any optically active material can be incorporated into the
      silica matrix to respond to solution pH or surface charge density variations. A
      direct application of this effect is for optical pH sensing which has very
      attractive features that can enable minimally invasive, remote, real time and
      continuous distributed pH monitoring. Particularly, as demonstrated here, using
      highly stable metal nanoparticles embedded in an inorganic silica matrix can
      significantly improve the capability of pH sensing in extremely harsh
      environments which is of increasing importance for applications in unconventional
      oil and gas resource recovery, carbon sequestration, water quality monitoring,
      etc. Our approach opens a pathway towards possible future development of robust
      optical pH sensors for the most demanding environmental conditions. The newly
      discovered optical effect of silica also offers the potential for control of the
      optical properties of optically active materials for a range of other potential
      applications such as electrochromic devices. 

PMID- 25572662
TI  - Circulating and disseminated tumor cells from breast cancer patient-derived
      xenograft-bearing mice as a novel model to study metastasis.
AB  - INTRODUCTION: Real-time monitoring of biologic changes in tumors may be possible
      by investigating the transitional cells such as circulating tumor cells (CTCs)
      and disseminated tumor cells in bone marrow (BM-DTCs). However, the small numbers
      of CTCs and the limited access to bone marrow aspirates in cancer patients pose
      major hurdles. The goal of this study was to determine whether breast cancer (BC)
      patient-derived xenograft (PDX) mice could provide a constant and renewable
      source of CTCs and BM-DTCs, thereby representing a unique system for the study of
      metastatic processes. METHODS: CTCs and BM-DTCs, isolated from BC PDX-bearing
      mice, were identified by immunostaining for human pan-cytokeratin and nuclear
      counterstaining of red blood cell-lysed blood and bone marrow fractions,
      respectively. The rate of lung metastases (LM) was previously reported in these
      lines. Associations between the presence of CTCs, BM-DTCs, and LM were assessed
      by the Fisher's Exact and Cochran-Mantel-Haenszel tests. Two separate genetic
      signatures associated with the presence of CTC clusters and with lung metastatic
      potential were computed by using the expression arrays of primary tumors from
      different PDX lines and subsequently overlapped to identify common genes.
      RESULTS: In total, 18 BC PDX lines were evaluated. CTCs and BM-DTCs, present as
      either single cells or clusters, were detected in 83% (15 of 18) and 62.5% (10
      to16) of the lines, respectively. A positive association was noted between the
      presence of CTCs and BM-DTCs within the same mice. LM was previously found in 9
      of 18 (50%) lines, of which all nine had detectable CTCs. The presence of LM was
      strongly associated with the detection of CTC clusters but not with individual
      cells or detection of BM-DTCs. Overlapping of the two genetic signatures of the
      primary PDX tumors associated with the presence of CTC clusters and with lung
      metastatic potential identified four genes (HLA-DP1A, GJA1, PEG3, and XIST). This
      four-gene profile predicted distant metastases-free survival in publicly
      available datasets of early BC patients. CONCLUSION: This study suggests that
      CTCs and BM-DTCs detected in BC PDX-bearing mice may represent a valuable and
      unique preclinical model for investigating the role of these rare cells in tumor
      metastases.

PMID- 25572665
TI  - PET/CT predicts survival in patients undergoing primary surgery for esophageal
      cancer.
AB  - INTRODUCTION: Positron emission tomography combined with computed tomography
      (PET/CT) is increasingly being used in the staging of esophageal cancer, and some
      recent studies suggested the maximal standardized uptake value (SUVmax) as a
      prognostic factor for prediction of survival of these patients. However, data on
      correlations between SUVmax and other established prognostic markers is rare, and
      the impact of neoadjuvant treatment on SUVmax ability to predict outcome is not
      clear. The aim of the present study was therefore to evaluate the prognostic
      significance of the SUVmax in patients with or without neoadjuvant therapy (NAT)
      by comparing SUVmax to different established prognostic factors and survival.
      METHODS: Esophageal cancer patients receiving either neoadjuvant therapy or no
      pretreatment before surgery were included in our study, and correlations between
      SUVmax and prognostic factors such as tumour/nodal stage, grading, tumour length
      or survival were investigated. RESULTS: Between January 2004 and December 2011, a
      total of 114 patients was included (mean age 63 years, 96 men, 36 SCC, 78
      adenocarcinoma). A number of 74 patients underwent neoadjuvant therapy. The
      median follow-up was 52 months. The SUVmax was significantly correlated to
      initial tumour stage (p = 0.000) and tumour length (p <= 0.010). Survival was
      significantly better in patients undergoing primary surgery if SUVmax was <6
      compared to SUVmax >6 (p = 0.008), whereas neither neoadjuvant-treated patients
      in general (p = 0.950) nor the different subgroups of responders showed a
      comparable correlation between survival and SUVmax (complete responder p = 0.808,
      partial responder p = 0.409, nonresponder p = 0.529). CONCLUSION: The SUVmax
      highly correlates with well-known prognostic factors and survival of esophageal
      cancer patients after surgery but only in case of primary surgery and not if
      patients received neoadjuvant therapy.

PMID- 25572666
TI  - Early experience with intensity modulated proton therapy for lung-intact
      mesothelioma: A case series.
AB  - PURPOSE: The purpose of this study was to describe our experience implementing
      intensity modulated proton therapy (IMPT) for lung-intact malignant pleural
      mesothelioma (MPM), including patient selection, treatment planning, dose
      verification, and process optimization. METHODS AND MATERIALS: Seven patients
      with epithelioid MPM were reviewed; 6 underwent pleurectomy, whereas 1 had biopsy
      alone. Four patients received IMPT and 3 received intensity modulated radiation
      therapy. Treatment plans for the other modality were created for dosimetric
      comparisons. Quality assurance processes included dose verification and
      robustness analysis. Image-guided setup was performed with the first isocenter,
      and couch shifts were applied to reposition to the second isocenter. RESULTS:
      Treatment with IMPT was well tolerated and completed without breaks. IMPT plans
      were designed with 2 isocenters, 4 beams, and <=64 energy layers per beam. Dose
      verification processes were completed in 3 hours. Total daily treatment time was
      approximately 45 minutes (20 minutes for setup and 25 minutes for delivery). IMPT
      produced lower mean doses to the contralateral lung, heart, esophagus, liver, and
      ipsilateral kidney, with increased contralateral lung sparing when mediastinal
      boost was required for nodal disease. CONCLUSIONS: Our initial experience showed
      that IMPT was feasible for routine care of patients with lung-intact MPM.

PMID- 25572667
TI  - Lineage specific expression of Polycomb Group Proteins in human embryonic stem
      cells in vitro.
AB  - Human embryonic (hES) stem cells are an excellent model to study lineage
      specification and differentiation into various cell types. Differentiation
      necessitates repression of specific genes not required for a particular lineage.
      Polycomb Group (PcG) proteins are key histone modifiers, whose primary function
      is gene repression. PcG proteins form complexes called Polycomb Repressive
      Complexes (PRCs), which catalyze histone modifications such as H2AK119ub1,
      H3K27me3, and H3K9me3. PcG proteins play a crucial role during differentiation of
      stem cells. The expression of PcG transcripts during differentiation of hES cells
      into endoderm, mesoderm, and ectoderm lineage is yet to be shown. In-house
      derived hES cell line KIND1 was differentiated into endoderm, mesoderm, and
      ectoderm lineages; followed by characterization using RT-PCR for HNF4A, CDX2,
      MEF2C, TBX5, SOX1, and MAP2. qRT-PCR and western blotting was performed to
      compare expression of PcG transcripts and proteins across all the three lineages.
      We observed that cells differentiated into endoderm showed upregulation of
      RING1B, BMI1, EZH2, and EED transcripts. Mesoderm differentiation was
      characterized by significant downregulation of all PcG transcripts during later
      stages. BMI1 and RING1B were upregulated while EZH2, SUZ12, and EED remained low
      during ectoderm differentiation. Western blotting also showed distinct expression
      of BMI1 and EZH2 during differentiation into three germ layers. Our study shows
      that hES cells differentiating into endoderm, mesoderm, and ectoderm lineages
      show distinct PcG expression profile at transcript and protein level. 

PMID- 25572668
TI  - Properties and determinants of codon decoding time distributions.
AB  - BACKGROUND: Codon decoding time is a fundamental property of mRNA translation
      believed to affect the abundance, function, and properties of proteins. Recently,
      a novel experimental technology--ribosome profiling--was developed to measure the
      density, and thus the speed, of ribosomes at codon resolution. Specifically, this
      method is based on next-generation sequencing, which theoretically can provide
      footprint counts that correspond to the probability of observing a ribosome in
      this position for each nucleotide in each transcript. RESULTS: In this study, we
      report for the first time various novel properties of the distribution of codon
      footprint counts in five organisms, based on large-scale analysis of ribosomal
      profiling data. We show that codons have distinctive footprint count
      distributions. These tend to be preserved along the inner part of the ORF, but
      differ at the 5' and 3' ends of the ORF, suggesting that the translation
      elongation stage actually includes three biophysical sub-steps. In addition, we
      study various basic properties of the codon footprint count distributions and
      show that some of them correlate with the abundance of the tRNA molecule types
      recognizing them. CONCLUSIONS: Our approach emphasizes the advantages of
      analyzing ribosome profiling and similar types of data via a comparative genomic
      codon-distribution-centric view. Thus, our methods can be used in future studies
      related to translation and even transcription elongation.

PMID- 25572669
TI  - Cognitive and behavioral determinants of psychotic symptoms in Alzheimer's
      disease.
AB  - AIMS: To investigate the relationship between psychotic symptoms and cognitive
      impairment in Alzheimer's disease (AD). METHODS: A total of 108 subjects affected
      by AD were subdivided into subjects without delusions (ND), subjects with
      paranoid delusions (PD), subjects with delusional misidentifications (DM),
      subjects with both DM and PD (DM+PD), subjects with visual hallucinations (v
      HALL), and subjects without visual hallucinations (N-HALL). RESULTS: PD and ND
      subjects performed similarly on neuropsychological tests, while DM patients
      performed significantly worse than PD and ND patients. v-HALL patients performed
      worse than N-HALL patients on memory, visuospatial, and executive functions. As
      for behavioral features, DM and v-HALL subjects reported higher scores on the
      abnormal motor behavior subscale of the neuropsychiatric inventory (NPI); PD
      subjects reported higher scores on the disinhibition subscale of the NPI. The
      severity of PD was predicted by the severity of disinhibition (B = 0.514; p =
      0.016) but not by neuropsychological performances. The severity of DM was
      predicted by age (B = 0.099; p = 0.048) and MMSE (B = -0.233; p = 0.001). The
      severity of v-HALL was predicted by age (B = 0.052; p = 0.037) and scores on an
      immediate visual memory task (B = -0.135; p = 0.007). CONCLUSIONS: The occurrence
      of PD may require the relative sparing of cognitive functions and be favored by
      frontal lobe dysfunction, while DM is associated with the overall level of
      cognitive impairment. Finally, v-HALL are associated with the impairment of
      visuospatial abilities.

PMID- 25572670
TI  - Effects of sleepiness on survival in Japanese hemodialysis patients: J-DOPPS
      study.
AB  - Sleep disorder and poor sleep quality are common in chronic hemodialysis (HD)
      patients. They have been claimed as a cause of morbidity and mortality. The
      relationship between the degree of sleepiness and survival has not been studied.
      We studied the degree of sleepiness in 1,252 adult HD patients (age >=20 years)
      recruited into the Dialysis Outcomes Practice Pattern Study in Japan (J-DOPPS
      III), using the Japanese version of the Epworth Sleepiness Scale (JESS)
      questionnaire. Demographic data were presented for three subgroups: low,
      intermediate, and high JESS score. Cox proportional hazard regression analysis
      was performed to estimate the independent effect of several variables on
      survival. The hazard ratio for mortality was 2.312 (95% CI 1.267-4.220; p =
      0.006) for those with a high JESS score (vs. those with a low JESS score) after
      adjusting for age, vintage (length of time on HD), sex, diabetes, body mass
      index, cardiovascular disease, HD treatment regimen (time, frequency, and single
      pool Kt/V), laboratory data (serum albumin, creatinine, and total cholesterol),
      and medication (antihypertensive drugs, erythropoietin, vitamin D, and phosphate
      binders). Patients >=70 years of age with comorbid conditions (congestive heart
      failure, stroke, and diabetes) showed a significantly higher JESS score (>=16).
      The JESS score did not show interaction by age. Results showed that the degree of
      sleepiness is related to survival in Japanese HD patients, particularly in
      elderly patients.

PMID- 25572671
TI  - Electronic nicotine delivery systems: a policy statement from the American
      Association for Cancer Research and the American Society of Clinical Oncology.
AB  - Combustible tobacco use remains the number-one preventable cause of disease,
      disability, and death in the United States. Electronic nicotine delivery systems
      (ENDS), which include electronic cigarettes, are devices capable of delivering
      nicotine in an aerosolized form. ENDS use by both adults and youth has increased
      rapidly, and some have advocated these products could serve as harm-reduction
      devices and smoking cessation aids. ENDS may be beneficial if they reduce smoking
      rates or prevent or reduce the known adverse health effects of smoking. However,
      ENDS may also be harmful, particularly to youth, if they increase the likelihood
      that nonsmokers or former smokers will use combustible tobacco products or if
      they discourage smokers from quitting. The American Association for Cancer
      Research (AACR) and the American Society of Clinical Oncology (ASCO) recognize
      the potential ENDS have to alter patterns of tobacco use and affect the health of
      the public; however, definitive data are lacking. The AACR and ASCO recommend
      additional research on these devices, including assessing the health impacts of
      ENDS, understanding patterns of ENDS use, and determining what role ENDS have in
      cessation. Key policy recommendations include supporting federal, state, and
      local regulation of ENDS; requiring manufacturers to register with the US Food
      and Drug Administration and report all product ingredients, requiring childproof
      caps on ENDS liquids, and including warning labels on products and their
      advertisements; prohibiting youth-oriented marketing and sales; prohibiting child
      friendly ENDS flavors; and prohibiting ENDS use in places where cigarette smoking
      is prohibited. This policy statement was developed by a joint writing group
      composed of members from the Tobacco and Cancer Subcommittee of the American
      Association for Cancer Research (AACR) Science Policy and Government Affairs
      (SPGA) Committee and American Society of Clinical Oncology (ASCO) Tobacco
      Cessation and Control Subcommittee of the Cancer Prevention Committee (CaPC). The
      statement was reviewed by both parent committees (ie, the AACR SPGA Committee and
      the ASCO CaPC) and was approved by the AACR Boards of Directors on August 6,
      2014, and the ASCO Executive Committee on September 18, 2014. This policy
      statement was published jointly by invitation and consent in both Clinical Cancer
      Research and Journal of Clinical Oncology. Copyright 2015 American Association
      for Cancer Research and American Society of Clinical Oncology. All rights
      reserved. No part of this document may be reproduced or transmitted in any form
      or by any means, electronic or mechanical, including photocopying, recording, or
      storage in any information storage and retrieval system, without written
      permission by the American Association for Cancer Research and the American
      Society of Clinical Oncology. 

PMID- 25572673
TI  - Monitoring of pile composting process of OFMSW at full scale and evaluation of
      odour emission impact.
AB  - In this study, the evolution of odour concentration (ouE/m(3)STP) emitted during
      the pile composting of the organic fraction of municipal solid waste (OFMSW) was
      monitored by dynamic olfactometry. Physical-chemical variables as well as the
      respirometric variables were also analysed. The aim of this work was twofold. The
      first was to determine the relationship between odour and traditional variables
      to determine if dynamic olfactometry is a feasible and adequate technique for
      monitoring an aerobic stabilisation process (composting). Second, the composting
      process odour impact on surrounding areas was simulated by a dispersion model.
      The results showed that the decrease of odour concentration, total organic carbon
      and respirometric variables was similar (around 96, 96 y 98% respectively). The
      highest odour emission (5224 ouE/m(3)) was reached in parallel with the highest
      microbiological activity (SOUR and OD20 values of 25 mgO2/gVS . h and 70
      mgO2/gVS, respectively). The validity of monitoring odour emissions during
      composting in combination with traditional and respirometric variables was
      demonstrated by the adequate correlation obtained between the variables.
      Moreover, the quantification of odour emissions by dynamic olfactometry and the
      subsequent application of the dispersion model permitted making an initial
      prediction of the impact of odorous emissions on the population. Finally, the
      determination of CO2 and CH4 emissions allowed the influence of composting
      process on carbon reservoirs and global warming to be evaluated.

PMID- 25572672
TI  - Divergent effects of the 'biased' 5-HT1 A receptor agonists F15599 and F13714 in
      a novel object pattern separation task.
AB  - BACKGROUND AND PURPOSE: Pattern separation, that is, the formation of distinct
      representations from similar inputs, is an important hippocampal process
      implicated in cognitive domains like episodic memory. A deficit in pattern
      separation could lead to memory impairments in several psychiatric and
      neurological disorders. Hence, mechanisms by which pattern separation can be
      increased are of potential therapeutic interest. EXPERIMENTAL APPROACH: 5-HT1A
      receptors are involved in spatial memory. Herein we tested the 'biased' 5-HT1A
      receptor agonists F15599, which preferentially activates post-synaptic
      heteroreceptors, and F13714, which preferentially activates raphe-located
      autoreceptors, in rats in a novel spatial task assessing pattern separation, the
      object pattern separation (OPS) task. KEY RESULTS: The acetylcholinesterase
      inhibitor donepezil, which served as a positive control, significantly improved
      spatial pattern separation at a dose of 1 mg.kg(-1) , p.o. F15599 increased
      pattern separation at 0.04 mg.kg(-1) , i.p., while F13714 decreased pattern
      separation at 0.0025 mg.kg(-1) , i.p. The selective 5-HT1A receptor antagonist
      WAY-100635 (0.63 mg.kg(-1) , s.c.) counteracted the effects of both agonists.
      These data suggest that acute preferential activation of post-synaptic 5-HT1A
      heteroreceptors improves spatial pattern separation, whereas acute preferential
      activation of raphe-located 5-HT1A autoreceptors impairs performance. CONCLUSIONS
      AND IMPLICATIONS: We successfully established and validated a novel, simple and
      robust OPS task and observed a diverging profile of response with 'biased' 5-HT1A
      receptor agonists based on their targeting of receptors in distinct brain
      regions. Our data suggest that the post-synaptic 5-HT1A receptor consists of a
      potential novel molecular target to improve pattern separation performance.

PMID- 25572674
TI  - LH-RH analogues in the treatment of young women with early breast cancer: long
      term follow-up of a phase II study.
AB  - To prevent premature ovarian failure (POF), high-risk, premenopausal women with
      early breast cancer were given a luteinizing-hormone releasing hormone (LH-RH)
      analogue during adjuvant chemotherapy. After an adriamycin-based regimen,
      patients received radiation therapy concomitant with cyclophosphamide,
      methotrexate and 5-fluorouracil. An aromatase inhibitor was given to patients
      positive for the estrogen receptor (ER+). The median age was 43 years (range, 26
      45). Among 200 consecutive patients, 46% had no axillary node, and 54% had a mean
      of 5.4 positive nodes (range, 1-25); 56% were ER+, 44% were estrogen receptor
      negative (ER-), 13% were triple negative, and 20 had tumors positive for the
      oncogene, c-erb-B2 (identified with fluorescent in situ hybridization). After a
      median follow-up of 105 months (range, 65-180), no patient under 40 years old
      exhibited POF, while 44% of patients over 40 years old exhibited POF. Eight
      pregnancies were recorded: 7 at term and 1 voluntary interruption. The 10-year
      disease-free survival and overall survival rates were 85 and 91%, respectively.
      These data showed that, in premenopausal patients with early breast cancer, the
      addition of an LH-RH analogue to adjuvant chemotherapy was well tolerated,
      prevented POF, and was associated with excellent disease-free survival and
      overall survival rates. 

PMID- 25572675
TI  - Cohort study of a simple 'Step-Up' regimen with the Asthma Control Test.
AB  - This prospective cohort study investigates whether simple guideline-based asthma
      management using a 'Step-Up' regimen with the Asthma Control Test score improves
      asthma control in patients with inadequately controlled asthma in primary care.
      Seventy out of ninety-three (75%) participants achieved a score of > 19 (good
      control), and the mean increase in Asthma Control Test score was 6.0 (95%
      confidence interval: 5.3-6.8), P < 0.001. The improvement was independent of
      baseline inhaled corticosteroid use.

PMID- 25572676
TI  - The colorectal cancer mortality-to-incidence ratio as an indicator of global
      cancer screening and care.
AB  - BACKGROUND: Disparities in cancer screening, incidence, treatment, and survival
      are worsening globally. The mortality-to-incidence ratio (MIR) has been used
      previously to evaluate such disparities. METHODS: The MIR for colorectal cancer
      is calculated for all Organisation for Economic Cooperation and Development
      (OECD) countries using the 2012 GLOBOCAN incidence and mortality statistics.
      Health system rankings were obtained from the World Health Organization. Two
      linear regression models were fit with the MIR as the dependent variable and
      health system ranking as the independent variable; one included all countries and
      one model had the "divergents" removed. RESULTS: The regression model for all
      countries explained 24% of the total variance in the MIR. Nine countries were
      found to have regression-calculated MIRs that differed from the actual MIR by
      >20%. Countries with lower-than-expected MIRs were found to have strong national
      health systems characterized by formal colorectal cancer screening programs.
      Conversely, countries with higher-than-expected MIRs lack screening programs.
      When these divergent points were removed from the data set, the recalculated
      regression model explained 60% of the total variance in the MIR. CONCLUSIONS: The
      MIR proved useful for identifying disparities in cancer screening and treatment
      internationally. It has potential as an indicator of the long-term success of
      cancer surveillance programs and may be extended to other cancer types for these
      purposes.

PMID- 25572677
TI  - Expression of fucosyltransferase 8 is associated with an unfavorable clinical
      outcome in non-small cell lung cancers.
AB  - Objecitive: Fucosyltransferase 8 (FUT8), the only enzyme responsible for the core
      alpha1,6-fucosylation of asparagine-linked oligosaccharides of glycoproteins, is
      a vital enzyme in cancer development and progression. We examined FUT8 expression
      in non-small cell lung cancers (NSCLCs) to analyze its clinical significance. We
      also examined the expression of guanosine diphosphate-mannose-4,6-dehydratase
      (GMD), which is imperative for the synthesis of fucosylated oligosaccharides.
      METHODS: Using immunohistochemistry, we evaluated the expression of FUT8 and GMD
      in relation to patient survival and prognosis in potentially curatively resected
      NSCLCs. RESULTS: High expression of FUT8 was found in 67 of 129 NSCLCs (51.9%)
      and was significantly found in non-squamous cell carcinomas (p = 0.008). High
      expression of FUT8 was associated with poor survival (p = 0.03) and was also a
      significant and independent unfavorable prognostic factor in patients with
      potentially curatively resected NSCLCs (p = 0.047). High expression of GMD was
      significantly associated with high FUT8 expression (p = 0.04). CONCLUSIONS: High
      expression of FUT8 is associated with an unfavorable clinical outcome in patients
      with potentially curatively resected NSCLCs, suggesting that FUT8 can be a
      prognostic factor. The analysis of FUT8 expression and its core fucosylated
      products may provide new insights for the therapeutic targets of NSCLCs.

PMID- 25572679
TI  - Omentum for Mammary Disorders: A 30-Year Systematic Review.
AB  - PURPOSE: Although the safety of applying omentum to the female breast for total
      breast reconstruction is controversial, it has recently been used to treat
      certain mammary disorders as well. A systematic review was therefore conducted to
      analyze and establish the suitability and safety of applying omentum to the
      breast. METHODS: Covereing the interval from January 1984 to December 2013, we
      performed searches in MEDLINE, Embase, SciELO, and Google-Scholar for original
      articles describing the applicability of greater omentum to the breast and its
      clinical complications. RESULTS: Sixty observational articles with 985 women were
      chosen. The main clinical indications were total breast reconstruction after
      mastectomy due to breast cancer (45 studies), radiation damage (23 studies), and
      congenital Poland syndrome (4 studies). Altogether, 273 complications were
      identified among the 985 women treated. The most frequent was flap necrosis
      (26.74 %). The most serious was injury to the digestive system (1.10 %). There
      was a 35.48 % incidence of local breast cancer recurrence in eight observational
      studies on oncological risk. Seven of the eight included only women with advanced
      cancer. One of these studies reported the incidence and relapse time
      predominantly according to the primary tumor size. CONCLUSIONS: Although the
      oncological risk remains unclear, there was a high volume of complications that
      affected the digestive system. These findings suggest that omentum has well
      established applicability, but only for total breast reconstruction of huge
      defects, where muscular/myocutaneous or perforator flaps may be unsuitable.

PMID- 25572680
TI  - Utility of Chemoresponse Assay in Patients Undergoing Cytoreductive Surgery Plus
      Hyperthermic Intraperitoneal Chemotherapy.
AB  - PURPOSE: Our aim was to evaluate the utility of in vitro drug sensitivity testing
      in patients with peritoneal surface malignancies undergoing cytoreductive surgery
      (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We found
      data for 27 patients who underwent CRS plus HIPEC from September 2009 to May 2012
      and whose tumors were submitted for in vitro drug sensitivity (ChemoFx((r))).
      Intraperitoneal chemotherapy agents included mitomycin C, cisplatin +
      doxorubicin, or cisplatin alone. RESULTS: There were 12 (44.4 %) appendiceal
      adenocarcinomas, 5 (18.5 %) colon cancers, 4 (14.8 %) sarcomas, 3 (11.1 %)
      ovarian cancers, 2 (7.4 %) mesotheliomas, and one (3.7 %) gastric cancer. In all,
      15 patients (55.5 %) underwent complete cytoreduction (CC <= 1). Seventeen tumors
      (63 %) displayed in vitro sensitivity to the agents used. Mean overall (OS) and
      progression-free (PFS) survivals for the entire group were 34.4 +/- 4.5 months
      (median 41 months) and 12.5 +/- 2.1 months (median 8 months), respectively. There
      were no significant differences in OS and PFS for patients whose tumors displayed
      in vitro drug sensitivity versus those whose tumors did not (p = 0.101 and p =
      0.403, respectively). These results also did not differ when evaluating only the
      patients who underwent complete cytoreduction. In vitro, the drug sensitivity did
      not correlate with primary tumor pathology or preoperative systemic chemotherapy
      administration. In vitro drug sensitivity correlated with the drug used at the
      time of HIPEC (p = 0.003). None of the tumors tested showed in vitro sensitivity
      to cisplatin and/or doxorubicin. Eight nonresponsive tumors, however, showed in
      vitro activity to other agents. CONCLUSIONS: Data indicate a high rate of in
      vitro resistance to the intraperitoneal chemotherapeutic agents used. In vitro
      drug sensitivity is not useful in patients undergoing CRS plus HIPEC.

PMID- 25572678
TI  - Association of SOX4 regulated by tumor suppressor miR-30a with poor prognosis in
      low-grade chondrosarcoma.
AB  - The sex-determining region Y-box 4 (SOX4), a transcription factor, is involved in
      various developmental processes. It has been reported in multiple human cancers.
      However, the prognostic value and its exact role in chondrosarcoma remain poorly
      understood. In the current study, SOX4 was overexpressed in 28 of 92 (30.4 %)
      interpretable chondrosarcoma patients compared with 3 of 43 (6.9 %) interpretable
      chondroma cases (P = 0.003). Its overexpression in chondrosarcoma was
      significantly associated with histological grade (P < 0.001) and the presence of
      tumor recurrence (P = 0.041). In addition, SOX4 overexpression was notably
      correlated with c-MYC (P = 0.011) and P53 (P = 0.029) expression as well as high
      Ki67 labeling index (LI) (P < 0.001) in our cohort. More importantly, we found
      that SOX4 was an unfavorable independent prognostic factor for chondrosarcoma
      patients with low histological grade. Functionally, SOX4 silencing significantly
      suppressed the proliferation, migratory, and invasive capacity of SW1353 cells,
      suggesting an oncogenic role of SOX4 in chondrosarcoma in vitro. In an attempt of
      characterizing SOX4 overexpression mechanism, we identified miR-30a as a tumor
      suppressor that directly targets SOX4 in chondrosarcoma cells. Clinically, miR
      30a expression was negatively correlated with SOX4 expression in chondrosarcoma
      cases. In all, we identified that SOX4 was oncogenic in chondrosarcoma and
      negatively regulated by miR-30a in vitro. Importantly, SOX4 overexpression may
      serve as a prognostic marker for patients with low-histological-grade
      chondrosarcoma.

PMID- 25572682
TI  - Establishing translational and clinical cancer research collaborations between
      high- and low-income countries.
AB  - Both infectious and noninfectious related malignancies are a growing problem in
      low- and middle-income countries (LMIC). It is difficult to extrapolate data and
      guidelines regarding cancer care from high-income countries (HIC) to cancer
      patients in LMIC. Due to the rise in noncommunicable cancer rates, there is a
      widening gap between the need for evidence-based treatments for cancer control
      plans and existing research capabilities. Surgeons frequently provide all
      surgical and medical oncology treatments for patients in LMIC for diseases, such
      as breast, gastric, cervical, and colorectal cancers. Surgical oncology clinical
      and translational research collaborations, however, are lacking. There are
      several successful consortiums that focus on HIV- and infectious-related
      malignancies. These collaborations can be used as an example for future surgical
      research efforts. The Memorial Sloan Kettering Cancer Center-Nigerian
      collaboration that is concentrating on colorectal cancer is used as an example of
      how to initiate a research collaboration that can build research infrastructure
      and provide the necessary data to generate realistic treatment guidelines. The
      need for expanded surgical oncology research and the growing population of
      patients with noninfectious-related malignancies in LMIC has created a unique
      opportunity for surgeons to initiate and lead clinical and translational research
      collaborations between HIC and LMIC. 

PMID- 25572681
TI  - Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for
      Pseudomyxoma Peritonei Arising from Urachus.
AB  - BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare locoregional disease
      characterized by disseminated intraperitoneal mucinous tumors. However, little is
      known about PMP from urachal neoplasm as a result of its rarity. METHODS: A total
      of 9 patients with PMP of urachal origin were treated by cytoreductive surgery
      (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in our institution.
      All specimens of surgeries were submitted for pathologic examination.
      Representative slides of tumors and normal urachus were submitted for
      immunohistochemical staining. RESULTS: Four patients were men; the median age was
      48 years (range 27-65 years). Initial radiologic examination of all patients
      showed a cystic tumor located between posterior aspect of umbilicus and the dome
      of urinary bladder, with or without leaking mucin. Complete CRS and HIPEC were
      performed in all patients. Until the latest follow-up, local recurrence occurred
      in 1 patient. Other 8 patients had a median disease-free survival of 27.5 months.
      Primary urachal tumors of 9 cases were all mucinous adenocarcinoma. Six patients
      had low-grade mucinous carcinoma peritonei, and 3 patients had high-grade
      mucinous carcinoma peritonei. Signet ring cells were noted in 4 patients. All
      tumor specimens of 9 patients were diffuse positive for CK-20, CDX-2, MUC-2, and
      MUC-5AC, and were variant positive for CK-7. CONCLUSIONS: PMP arising from
      urachus comes from neoplastic cells with development of intestinal-type mucinous
      neoplasm. It shares a similar pathophysiology as PMP from appendix. CRS including
      total urethrectomy, partial cystectomy, and peritonectomy plus HIPEC can be
      considered as a new option of treatment for PMP originating from urachus.

PMID- 25572683
TI  - Global surgical oncology: addressing the global surgical oncology disease burden.

PMID- 25572684
TI  - Factors affecting cytokine change after esophagectomy for esophageal cancer.
AB  - BACKGROUND: Esophagectomy for esophageal cancer is one of the most invasive
      operative procedures. Surgical stress induces the release of proinflammatory
      cytokines, and overproduction induces a systemic inflammatory response syndrome,
      which may lead to acute lung injury and multiple organ dysfunction syndrome. In
      addition, surgical stress may cause immunosuppression, which may affect not only
      perioperative mortality but also long-term survival. METHODS: Between 2006 and
      2013, levels of perioperative serum cytokines were evaluated in 90 patients who
      underwent esophagectomy for esophageal carcinoma. The serum interleukin (IL)-6,
      IL-8, and IL-10 levels were measured by enzyme-linked immunosorbent assays. We
      reviewed and assessed medical records, including cytokine profiles, and
      determined the factors affecting postoperative serum cytokine levels. RESULTS:
      These cytokine levels peaked on postoperative day 1 and decreased gradually. Of
      the clinicopathologic factors, a thoracoscopic approach was a significant factor
      in attenuating IL-6 and IL-8 levels on postoperative day 1 in multivariate
      analysis, and a longer operative time was a significant factor in increasing
      these levels. During postoperative days 3-7, the thoracoscopic approach and early
      enteral nutrition were significant factors in attenuating serum cytokine changes
      in multivariate analysis, and postoperative infectious complications were
      significant factors in increasing these levels. CONCLUSIONS: The thoracoscopic
      approach and early enteral nutrition could attenuate the cytokine change after
      esophagectomy, and a longer operative time and postoperative infectious
      complication could increase it. We should undertake strategies to minimize the
      surgical stress to reduce potential short-term and long-term consequences for
      patients.

PMID- 25572685
TI  - Medullary colorectal carcinoma revisited: a clinical and pathological study of
      102 cases.
AB  - AIM: Medullary carcinoma is a recently described subtype of mismatch repair
      deficient (MMRd) colorectal carcinoma (CRC) which, despite being poorly
      differentiated by traditional morphological criteria, has been reported to have a
      good prognosis. We investigated the pathological and clinical features of
      medullary CRC in an unselected cohort of CRCs undergoing surgical resection.
      METHODS: All CRCs resected within a single health district database from 1998 to
      2012 were categorized prospectively and underwent retrospective review to
      identify 91 medullary CRCs, with 11 additional cases from 2013 to 2014. Strict
      criteria were employed to diagnose medullary carcinoma requiring both MMRd and
      greater than 90 % of the tumor to demonstrate typical morphology, including solid
      growth. The demographic and pathological features, as well as all-cause survival,
      were compared with other CRCs, and specifically to other MMRd CRCs. RESULTS: From
      1998 to 2012, 91 of 3,295 CRCs (2.8 %) were of the medullary type. Medullary CRC
      was more likely to arise in females than males (3.3:1; p < 0.0001), the elderly
      (mean age 77 vs. 71 years; p < 0.001), and the right colon (86 %; p < 0.0001).
      All medullary CRCs demonstrated MMR deficiency (considered an inclusion criteria)
      and 86 % were BRAFV600E-mutated (p < 0.0001). Thirty-day mortality after
      resection was higher in medullary CRC (4.6 vs. 1.7 %; p = 0.049). On univariate
      analysis, survival was not better than well-differentiated or other MMRd tumors.
      However, using a multivariate model, a medullary phenotype was protective (hazard
      ratio of death 0.54, 95 % CI 0.30-0.96; p = 0.037). CONCLUSIONS: Medullary CRC is
      more common than previously reported, frequently presents with locally advanced
      disease, and may be associated with higher mortality at 30 days after resection.
      Despite this, when strict criteria are used for diagnosis, the overall survival
      is favorable when compared with CRCs with equivalent demographic and pathological
      characteristics.

PMID- 25572686
TI  - Recurrence After Partial Hepatectomy for Metastatic Colorectal Cancer:
      Potentially Curative Role of Salvage Repeat Resection.
AB  - PURPOSE: Patients with recurrence after complete resection of colorectal liver
      metastases (CLM) are considered for repeat resection as a potential salvage
      therapy (PST). However, outcomes for this approach are not well defined. We
      sought to analyze the natural history of recurrence and PST in a large cohort of
      patients with long-term follow-up. METHODS: Recurrence patterns, treatments, and
      outcomes in consecutive patients undergoing resection for colorectal liver
      metastases were analyzed retrospectively. PST was defined as repeat resection of
      all recurrent disease and effective salvage therapy (EST) as free of disease for
      36 months after last PST. Factors associated with PST, EST, and outcomes were
      analyzed. RESULTS: Of 952 patients who underwent resection, 594 (62 %)
      experienced recurrence (median interval = 13 months). Initial recurrences
      involved liver (n = 157,26 %), lung (n = 167,28 %), multiple sites (n = 171,29
      %), and other single sites (n = 99,17 %). PST was performed in 160 (27 %) of 594,
      most commonly with a single site of recurrence (n = 149). Young age (p = 0.01),
      negative initial resection margin (p = 0.003), initial tumor size <5 cm (p =
      0.006), and recurrence pattern (p < 0.001) were independently associated with
      PST. Thirty-six patients experienced EST (25 % of PSTs). Overall median survival
      was 61 and 43 months in those with recurrence. Median survival of patients
      undergoing PST was 87 months compared to 34 months for those who did not.
      CONCLUSIONS: Recurrence is common after CLM resection, but 27 % of patients were
      able to undergo PST. Approximately one-quarter of these experienced EST and may
      be cured. PST is associated with long-term survival and possible cure, and
      therefore active surveillance after CLM resection is justified.

PMID- 25572688
TI  - Construction of a supported Ru complex on bifunctional MOF-253 for photocatalytic
      CO2 reduction under visible light.
AB  - A MOF-253 supported active Ru carbonyl complex (MOF-253-Ru(CO)2Cl2) was
      constructed for photocatalytic CO2 reduction under visible light irradiation. Its
      performance can be further improved by immobilization as a photosensitizer. This
      study highlights the great potential of using MOFs as a solid ligand and platform
      for the assembly of a complicated catalytic system. 

PMID- 25572687
TI  - Preoperative carboplatin-paclitaxel-bevacizumab in triple-negative breast cancer:
      final results of the phase II Ca.Pa.Be study.
AB  - PURPOSE: The phase II Ca.Pa.Be trial evaluated preoperative carboplatin
      paclitaxel in combination with bevacizumab in triple-negative breast cancer
      patients with previously untreated stage II-III disease. The primary aim was the
      assessment of the rate of pathologic complete response (pCR). Secondary aims
      included safety, breast-conserving surgery rate, and early response assessment
      with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS:
      Patients with hormone receptor-negative, HER-2-negative stage II-III breast
      cancer were eligible. Treatment included paclitaxel 80 mg/mq + carboplatin area
      under the curve (AUC) 2 on days 1, 8, and 15, combined with bevacizumab 10 mg/kg
      on days 1 and 15 each 28 days, for 5 courses. At baseline, patients underwent
      breast DCE-MRI, followed by a single dose of bevacizumab 5 mg/kg (day -6). DCE
      MRI was repeated before the initiation of chemotherapy. RESULTS: Forty-four
      patients were enrolled. Forty-three patients underwent surgery, and 22 (50 %)
      received breast-conserving surgery (conversion rate from mastectomy indication at
      baseline, 34.4 %). A pCR in breast and axillary lymph nodes occurred in 22
      patients (50 %). Bevacizumab-associated adverse events (AEs) were mild: G1-2
      hypertension and bleeding occurred in 6 (13.6 %) and 12 (27 %) patients,
      respectively. No G4 nonhematologic AEs were recorded. More frequent G3 AEs were
      liver function test abnormalities (6.8 %), and diarrhea and fatigue (4.5 % each).
      The only G3-4 hematologic toxicity was neutropenia (G3, 25 %; G4, 9 %). Early
      assessed DCE-MRI response parameters failed to predict pCR. CONCLUSIONS: The
      neoadjuvant anthracycline-free combination of weekly paclitaxel and carboplatin
      plus bevacizumab is active and safe in triple-negative breast cancer, and the
      rate of pCR is comparable to that observed with more intensive carboplatin- and
      bevacizumab-containing regimens. Further investigation is warranted.

PMID- 25572689
TI  - Determination of breath acetone in 149 type 2 diabetic patients using a ringdown
      breath-acetone analyzer.
AB  - Over 90% of diabetic patients have Type 2 diabetes. Although an elevated mean
      breath acetone concentration has been found to exist in Type 1 diabetes (T1D),
      information on breath acetone in Type 2 diabetes (T2D) has yet to be obtained. In
      this study, we first used gas chromatography-mass spectrometry (GC-MS) to
      validate a ringdown breath-acetone analyzer based on the cavity-ringdown
      spectroscopy technique, through comparing breath acetone concentrations in the
      range 0.5-2.5 ppm measured using both methods. The linear fitting of R = 0.99
      suggests that the acetone concentrations obtained using both methods are
      consistent with a largest standard deviation of +/-0.4 ppm in the lowest
      concentration of the range. Next, 620 breath samples from 149 T2D patients and 42
      healthy subjects were collected and tested using the breath analyzer. Four breath
      samples were taken from each subject under each of four different conditions:
      fasting, 2 h post-breakfast, 2 h post-lunch, and 2 h post-dinner. Simultaneous
      blood glucose levels were also measured using a standard diabetic-management
      blood-glucose meter. For the 149 T2D subjects, their exhaled breath acetone
      concentrations ranged from 0.1 to 19.8 ppm; four different ranges of breath
      acetone concentration, 0.1-19.8, 0.1-7.1, 0.1-6.3, and 0.1-9.5 ppm, were obtained
      for the subjects under the four different conditions, respectively. For the 42
      healthy subjects, their breath acetone concentration ranged from 0.1 to 2.6 ppm;
      four different ranges of breath acetone concentration, 0.3-2.6, 0.1-2.6, 0.1-1.7,
      and 0.3-1.6 ppm, were obtained for the four different conditions. The mean breath
      acetone concentration of the 149 T2D subjects was determined to be 1.5 +/- 1.5
      ppm, which was 1.5 times that of 1.0 +/- 0.6 ppm for the 42 healthy subjects. No
      correlation was found between the breath acetone concentration and the blood
      glucose level of the T2D subjects and the healthy volunteers. This study using a
      relatively large number of subjects provides new data regarding breath acetone in
      diabetes (T1D and T2D) and suggests that an elevated mean breath acetone
      concentration also exists in T2D.

PMID- 25572690
TI  - Development and in-house validation of an allergen-specific ELISA for
      quantification of Bet v 4 in diagnostic and therapeutic birch allergen products.
AB  - Birch (Betula) pollen is a major cause of allergy in northern and central Europe.
      The allergenic potency of products for diagnosis and therapy of birch pollen
      allergy is adjusted nearly exclusively to the major birch pollen allergen Bet v
      1. Although every fifth patient is additionally sensitized to Bet v 4, both
      content and variability of this minor allergen in birch allergen products remain
      unclear due to a lack of simple and cost-effective quantitative methods. This
      study aimed to develop and in-house validate the first Bet v 4-specific sandwich
      enzyme-linked immunosorbent assay (ELISA). Based on a murine monoclonal antibody
      in combination with a polyclonal rabbit antiserum, the ELISA proved to be highly
      sensitive, with a lower limit of quantification of 30 pg/ml Bet v 4. After
      confirmation of satisfactory accuracy, reproducibility, and robustness, the ELISA
      was utilized to quantify Bet v 4 in 30 authorized birch allergen products. The
      allergen was detected in all samples tested, ranging from 0.2 to 4.4 MUg/ml. No
      significant correlation of Bet v 4 was found with the respective amount of Bet v
      1. In contrast to Bet v 1, also no correlation of Bet v 4 with total protein
      content or total allergenic activity could be observed. Thus, it seems presently
      unfeasible to base birch allergen product standardization additionally on Bet v
      4. In light of these results, the continuous monitoring of Bet v 4 in birch
      allergen products with the presented ELISA will provide a basis for the
      understanding of the clinical relevance of minor allergens.

PMID- 25572691
TI  - The role of physico-chemical and bulk characteristics of co-spray dried L-leucine
      and polyvinylpyrrolidone on glidant and binder properties in interactive
      mixtures.
AB  - In this study, polyvinylpyrrolidone (PVP) was spray dried with l-leucine (PVP
      Leu) to create a prototype multifunctional interactive excipient. The physico
      chemical and bulk properties such as particle size, surface composition, surface
      energy and bulk cohesion of PVP-Leu was measured and compared against pure spray
      dried PVP (PVP-SD). The mixing behaviour of these excipients and their effect on
      flow and binder activity of paracetamol was assessed. The mean particle sizes of
      PVP-Leu PVP-SD and PVP were 2.5, 2.1 and 21.9MUm, respectively. Surface
      composition characterization indicated that l-leucine achieved higher
      concentrations on the surface compared to the bulk of the PVP-Leu particles. The
      surface energy of PVP-Leu was significantly lower compared to PVP-SD. In
      addition, PVP-Leu exhibited a significantly lower bulk cohesion compared PVP-SD.
      The excipients were blended with paracetamol and qualitative characterization
      indicated that PVP-Leu blended more homogeneously with paracetamol compared to
      PVP-SD. Both PVP-Leu and PVP-SD then exhibited a significantly improved binder
      activity compared to PVP. The flow of the paracetamol was markedly improved with
      PVP-Leu while PVP-SD and PVP had negligible effect on its flow. This study
      reveals how physico-chemical and bulk properties of such prototype interactive
      excipients can play a key role in determining multi-factorial excipient
      performance. 

PMID- 25572694
TI  - Erratum to: effects of calmodulin on expression of lignin-modifying enzymes in
      Pleurotus ostreatus.

PMID- 25572692
TI  - Resveratrol nanoformulations: challenges and opportunities.
AB  - Resveratrol, a naturally occurring polyphenol and phytoalexin, has received
      significant attention in recent years due to its vast therapeutic effects
      including anticancer, antioxidant and anti-inflammatory effects. However, poor
      pharmacokinetic properties such as low aqueous solubility, low photostability and
      extensive first pass metabolism result in poor bioavailability, hindering its
      immense potential. Conventional dosage forms such as dry powder capsules and
      injections have met with limited success, demonstrating challenges faced in
      developing an effective formulation. Recently, nanotechnology-based formulations
      (nanoformulations) are being looked upon as a novel method for improving the
      pharmacokinetic properties, as well as enhancing targetability and
      bioavailability of resveratrol. This review outlines the therapeutic potential of
      resveratrol, explores its mechanisms of action and pharmacokinetic limitations,
      and discusses the success and challenges of resveratrol-encapsulated
      nanoparticles in the last decade. Potential techniques to improve encapsulation
      of the drug within nanoparticles, thereby enhancing its clinical potential are
      highlighted. 

PMID- 25572695
TI  - Anti-proliferative effects of polyphenols from pomegranate rind (Punica granatum
      L.) on EJ bladder cancer cells via regulation of p53/miR-34a axis.
AB  - miRNAs and their validated miRNA targets appear as novel effectors in biological
      activities of plant polyphenols; however, limited information is available on miR
      34a mediated cytotoxicity of pomegranate rind polyphenols in cancer cell lines.
      For this purpose, cell viability assay, Realtime quantitative PCR for mRNA
      quantification, western blot for essential protein expression, p53 silencing by
      shRNA and miR-34a knockdown were performed in the present study. EJ cell
      treatment with 100 ug (GAE)/mL PRE for 48 h evoked poor cell viability and
      caspase-dependent pro-apoptosis appearance. PRE also elevated p53 protein and
      triggered miR-34a expression. The c-Myc and CD44 were confirmed as direct targets
      of miR-34a in EJ cell apoptosis induced by PRE. Our results provide sufficient
      evidence that polyphenols in PRE can be potential molecular clusters to suppress
      bladder cancer cell EJ proliferation via p53/miR-34a axis.

PMID- 25572696
TI  - Synthesis and characterisation of nickel Schiff base complexes containing the
      meso-1,2-diphenylethylenediamine moiety: selective interactions with a
      tetramolecular DNA quadruplex.
AB  - As part of a program of preparing metal complexes which exhibit unique affinities
      towards different DNA structures, we have synthesised the novel Schiff base
      complex N,N'-bis-4-(hydroxysalicylidine)meso-diphenylethylenediaminenickel(ii)
      (), via the reaction of meso-1,2-diphenylethylenediamine and 2,4
      dihydroxybenzaldehyde. This compound was subsequently reacted with 1-(2
      chloroethyl)piperidine or 1-(2-chloropropyl)piperidine, to afford the alkylated
      complexes N,N'-bis-(4-((1-(2-ethyl)piperidine)oxy)salicylidine)meso-1,2
      diphenylethylenediaminenickel(ii) () and N,N'-bis-(4-((1-(3
      propyl)piperidine)oxy)-salicylidine)meso-1,2-diphenylethylenediaminenickel(ii)
      (), respectively. These complexes were characterised by microanalysis and X-ray
      crystallography in the solid state, and in solution by (1)H and (13)C NMR
      spectroscopy. Electrospray ionisation mass spectrometry (ESI-MS) was used to
      confirm the identity of () and (). The affinities of () and () towards a discrete
      16 mer duplex DNA molecule, and examples of both tetramolecular and unimolecular
      DNA quadruplexes, was explored using a variety of techniques. In addition, the
      affinity of two other complexes () and (), towards the same DNA molecules was
      examined. Complexes () and () were prepared by methods analogous to those which
      afforded () and (), however 1,2-phenylenediamine was used instead of meso-1,2
      diphenylethylenediamine in the initial step of the synthetic procedure. The
      results of ESI-MS and DNA melting temperature measurements suggest that () and ()
      exhibit a lower affinity than () and () towards the 16 mer duplex DNA molecule,
      while circular dichroism (CD) spectroscopy suggested that none of the four
      complexes had a major effect on the conformation of the nucleic acid. In
      contrast, ESI-MS and CD spectroscopy suggested that both () and () show
      significant binding to a tetramolecular DNA quadruplex. The results of ESI-MS and
      Fluorescence Resonance Energy Transfer (FRET) assays indicated that () and () did
      not bind as tightly to a unimolecular DNA quadruplex, although both complexes had
      a major effect on the CD spectrum of the latter. These results highlight that the
      presence of the meso-1,2-diphenylethylenediamine moiety in metal complexes of
      this type may provide a general method for instilling selectivity for some DNA
      quadruplexes over dsDNA. 

PMID- 25572697
TI  - Lessons learned from research on air pollution and other particles in the
      toxicology of nanomaterials and vice versa.

PMID- 25572693
TI  - Damage response involves mechanisms conserved across plants, animals and fungi.
AB  - All organisms are constantly exposed to adverse environmental conditions
      including mechanical damage, which may alter various physiological aspects of
      growth, development and reproduction. In plant and animal systems, the damage
      response mechanism has been widely studied. Both systems posses a conserved and
      sophisticated mechanism that in general is aimed at repairing and preventing
      future damage, and causes dramatic changes in their transcriptomes, proteomes,
      and metabolomes. These damage-induced changes are mediated by elaborate signaling
      networks, which include receptors/sensors, calcium (Ca(2+)) influx, ATP release,
      kinase cascades, reactive oxygen species (ROS), and oxylipin signaling pathways.
      In contrast, our current knowledge of how fungi respond to injury is limited,
      even though various reports indicate that mechanical damage triggers reproductive
      processes. In fungi, the damage response mechanism has been studied more in depth
      in Trichoderma atroviride. Interestingly, these studies indicate that the
      mechanical damage response involves ROS, Ca(2+), kinase cascades, and lipid
      signaling pathways. Here we compare the response to mechanical damage in plants,
      animals and fungi and provide evidence that they appear to share signaling
      molecules and pathways, suggesting evolutionary conservation across the three
      kingdoms. 

PMID- 25572699
TI  - Role of calcium-sensing receptor in cardiac injury of hereditary epileptic rats.
AB  - BACKGROUND: It has been reported that epilepsy leads to cardiac injury, but the
      underlying mechanisms have not yet been elucidated. Studies indicated that the
      calcium-sensing receptor (CaSR) is involved in cardiomyocyte apoptosis. However,
      the role of CaSR in epilepsy-induced cardiac injury remains unclear. OBJECTIVE:
      The aim of this study was to investigate the effects of CaSR on cardiac injury of
      hereditary epileptic rats. METHODS: The tremor (TRM) rat was used as an epilepsy
      model. Apoptotic rate, collagen volume fraction, and the expression of CaSR, Bcl
      2, Bax, caspase-3, extracellular signal-regulated protein kinase (ERK), c-Jun NH2
      terminal protein kinase (JNK), p38 mitogen-activated protein kinase (MAPK),
      transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor
      (CTGF), collagen I and collagen III protein were analyzed. RESULTS: The results
      showed that the CaSR protein was increased in TRM rat hearts. Cardiac apoptosis
      and fibrosis were also observed by terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling (TUNEL) and Masson's trichrome staining, respectively.
      Further results demonstrated that the expression of Bax, caspase-3, P-JNK, P-p38,
      TGF-beta1, CTGF, collagen I and collagen III protein were upregulated, whereas
      Bcl-2 and P-ERK were downregulated in TRM rat hearts. Moreover, these deleterious
      changes were further aggravated by GdCl3 and attenuated by NPS-2390. CONCLUSIONS:
      Our results suggest that CaSR promotes cardiac apoptosis and fibrosis in TRM rat
      through the induction of mitochondrial and MAPK pathways as well as the
      activation of TGF-beta1 and CTGF.

PMID- 25572698
TI  - Wnt3a increases the metastatic potential of non-small cell lung cancer cells in
      vitro in part via its upregulation of Notch3.
AB  - Metastasis is the leading cause of death in lung cancer. Understanding the
      mechanisms underlying the process of metastasis is crucial for identifying novel
      anti-metastatic therapies. Studies indicate that the highly conserved
      developmental pathways, such as the Wnt and Notch signaling pathways, play
      important roles in the non-small cell lung cancer (NSCLC) tumorigenesis. However,
      the roles of both pathways in NSCLC metastasis are unclear. The present study
      aimed to investigate whether Wnt3a and Notch3, key components of the Wnt and
      Notch signaling pathways, respectively, regulate the metastatic abilities of
      NSCLC cells and whether there is some relationship during these regulatory
      events. Here, we observed that Wnt3a treatment upregulated, not only the protein
      expression of Notch3, but also the mRNA expression of Notch3 and its downstream
      genes, HES1 and HEYL. In addition, Wnt3a promoted cell invasion and anchorage
      independent growth. Meanwhile, Wnt3a treatment caused epithelial-mesenchymal
      transition (EMT)-like morphological changes and F-actin reorganization. The
      western blotting data showed that Wnt3a treatment decreased the expression of E
      cadherin and increased the expression of N-cadherin and vimentin. Compared with
      Wnt3a treatment, Notch3 shRNA transfection had opposite effects. Furthermore,
      Notch3 shRNA weakened the effects of Wnt3a treatment on the in vitro cell
      invasion and EMT. Overall, these observations suggest that Wnt3a and Notch3 may
      promote the metastasis of NSCLC and Notch3 upregulation is required for the Wnt3a
      mediated increased metastatic abilities of NSCLC.

PMID- 25572700
TI  - T cell tyrosine phosphorylation response to transient redox stress.
AB  - Reactive Oxygen Species (ROS) are crucial to multiple biological processes
      involved in the pathophysiology of inflammation, and are also involved in redox
      signaling responses. Although previous reports have described an association
      between oxidative events and the modulation of innate immunity, a role for redox
      signaling in T cell mediated adaptive immunity has not been described yet. This
      work aims at assessing if T cells can sense redox stress through protein
      sulfhydryl oxidation and respond with tyrosine phosphorylation changes. Our data
      show that Jurkat T cells respond to -SH group oxidation with specific tyrosine
      phosphorylation events. The release of T cell cytokines TNF, IFNgamma and IL2 as
      well as the expression of a number of receptors are affected by those changes.
      Additionally, experiments with spleen tyrosine kinase (Syk) inhibitors showed a
      major involvement of Syk in these responses. The experiments described herein
      show a link between cysteine oxidation and tyrosine phosphorylation changes in T
      cells, as well as a novel mechanism by which Syk inhibitors exert their anti
      inflammatory activity through the inhibition of a response initiated by ROS.

PMID- 25572701
TI  - Studying lipoprotein trafficking in zebrafish, the case of chylomicron retention
      disease.

PMID- 25572702
TI  - Development and selection of Asian-specific humeral implants based on statistical
      atlas: toward planning minimally invasive surgery.
AB  - PURPOSE: The commercial humeral implants based on the Western population are
      currently not entirely compatible with Asian patients, due to differences in bone
      size, shape and structure. Surgeons may have to compromise or use different
      implants that are less conforming, which may cause complications of as well as
      inconvenience to the implant position. The construction of Asian humerus atlases
      of different clusters has therefore been proposed to eradicate this problem and
      to facilitate planning minimally invasive surgical procedures [6,31]. According
      to the features of the atlases, new implants could be designed specifically for
      different patients. Furthermore, an automatic implant selection algorithm has
      been proposed as well in order to reduce the complications caused by implant and
      bone mismatch. METHODS: Prior to the design of the implant, data clustering and
      extraction of the relevant features were carried out on the datasets of each
      gender. The fuzzy C-means clustering method is explored in this paper. Besides,
      two new schemes of implant selection procedures, namely the Procrustes analysis
      based scheme and the group average distance-based scheme, were proposed to better
      search for the matching implants for new coming patients from the database. Both
      these two algorithms have not been used in this area, while they turn out to have
      excellent performance in implant selection. Additionally, algorithms to calculate
      the matching scores between various implants and the patient data are proposed in
      this paper to assist the implant selection procedure. RESULTS: The results
      obtained have indicated the feasibility of the proposed development and selection
      scheme. The 16 sets of male data were divided into two clusters with 8 and 8
      subjects, respectively, and the 11 female datasets were also divided into two
      clusters with 5 and 6 subjects, respectively. Based on the features of each
      cluster, the implants designed by the proposed algorithm fit very well on their
      reference humeri and the proposed implant selection procedure allows for a
      scenario of treating a patient with merely a preoperative anatomical model in
      order to correctly select the implant that has the best fit. Based on the leave
      one-out validation, it can be concluded that both the PA-based method and GAD
      based method are able to achieve excellent performance when dealing with the
      problem of implant selection. The accuracy and average execution time for the PA
      based method were 100 % and 0.132 s, respectively, while those of the GAD- based
      method were 100 % and 0.058 s. Therefore, the GAD-based method outperformed the
      PA-based method in terms of execution speed. CONCLUSION: The primary
      contributions of this paper include the proposal of methods for development of
      Asian-, gender- and cluster-specific implants based on shape features and
      selection of the best fit implants for future patients according to their
      features. To the best of our knowledge, this is the first work that proposes
      implant design and selection for Asian patients automatically based on features
      extracted from cluster-specific statistical atlases.

PMID- 25572703
TI  - Automatic detection of coronary artery anastomoses in epicardial ultrasound
      images.
AB  - PURPOSE: Epicardial ultrasound (EUS) can be used to assess the quality of
      coronary artery bypass graft surgery (CABG) anastomoses by determining stenotic
      rates. Currently, no objective quantitative methods are available for the
      analysis of EUS images. Therefore, surgeons have to be trained in interpreting
      EUS images, which may limit the use of EUS in clinical practice. Automatic
      detection of vessel structures can enable the objective and quantitative quality
      assessment of anastomoses without user interaction to facilitate the revision of
      anastomoses during the primary surgery. METHODS: An automatic vessel detection
      algorithm extracted and detected image regions that uniquely intersected with the
      vessel lumen of anastomotic structures. First, an initial pixel-based
      segmentation was performed from regional minimums using a watershed segmentation
      and an adaptive thresholding approach. A region-based merging step was then
      performed to merge oversegmented vessel structures using a Bayesian
      classification of different region combinations constructed from the pixel-based
      segmentations. Finally, a vessel classification step was performed on the
      extracted regions after the region-based merging to determine the probabilities
      that the regions contained vessel structures. RESULTS: The performance of the
      vessel classifier was tested using m-fold cross-validation of 320 EUS images
      containing anastomotic vessel structures from 16 anastomoses made on healthy
      porcine vessels. An area under the curve of 0.966 (95 % CI 0.951-0.984) and 0.989
      (95 % CI 0.985-0.993, p < 0.001) of a precision-recall and receiver operator
      characteristic curve, respectively, was obtained when detecting vessel regions
      extracted from the EUS images. CONCLUSIONS: The vessel detection algorithm can
      detect vessel regions in EUS images at a high accuracy. It can be used to enable
      the automatic analysis of EUS images for the quality assessment of CABG
      anastomoses.

PMID- 25572705
TI  - North American Spine Society presidential address.

PMID- 25572704
TI  - Axial perspective to find the largest intraosseous space available for
      percutaneous screw fixation of fractures of the acetabular anterior column.
AB  - OBJECTIVE: To find the largest screw path in the acetabular anterior column using
      a novel method of axial perspective and test the clinical feasibility of the
      anterior column axial view projection. METHODS: 3D models with the inner
      triangular patches deleted were created from the pelvic CT scan data of 58 normal
      pelvises. The transparency of each 3D model was downgraded at the axial
      perspective (the view perpendicular to the cross section of the anterior column
      axis) so that a translucent area was seen clearly. The orientations of each 3D
      model were adjusted until a triangle-like translucent area that could accommodate
      the largest virtual screw (Screw I) was present and then an ellipse-like
      translucent area that could accommodate the two largest virtual screws (Screw II)
      was present. The maximum diameter, direction of Screw I and the maximum diameter
      Screw II were measured. Clinical feasibility of the axial view projection was
      next tested in five cadaveric specimens. RESULTS: The mean maximum diameters of
      Screw I and Screw II were 11.20 +/- 1.73 (7.80-14.60 mm) and 8.71 +/- 0.91 (6.60
      10.60 mm), respectively. The angles of Screw I to the transverse, coronal and
      sagittal planes were 41.16 degrees  +/- 4.59 degrees , 18.18 degrees  +/- 1.15
      degrees  and 44.33 degrees  +/- 4.31 degrees , respectively. Translucent areas
      were successfully observed in all the cadaveric hemi-pelves and guide pins were
      successfully inserted in all the cadaveric hemi-pelves with the assistance of the
      anterior column axial view projection without cortex penetration or joint
      violation. CONCLUSIONS: The acetabular anterior column could safely accommodate
      not only one 7.3-mm screw, but also two 6.5-mm screws. The anterior column axial
      projection may be clinically feasible.

PMID- 25572706
TI  - Baclofen as add-on to standard psychosocial treatment for alcohol dependence: a
      randomized, double-blind, placebo-controlled trial with 1 year follow-up.
AB  - BACKGROUND: Limited clinical trials and case-reports yielded conflicting results
      regarding the efficacy of baclofen (a GABAB agonist) in the treatment of alcohol
      dependence. The aim of this study was to test the efficacy and tolerability of
      baclofen in alcohol dependent patients in Israel. METHODS: The study was a double
      blind, placebo-controlled, randomized trial comparing 50mg/day of baclofen to
      placebo over 12 weeks, in addition to a standard psychosocial intervention
      program, with 26-week and 52-week follow-up observations. The percentages of
      heavy drinking days and abstinent days were the primary outcome measures, and
      craving, distress and depression levels; self-efficacy; social support from
      different sources; and health-related quality of life (HRQL) were secondary
      outcomes. Tolerability was also examined. RESULTS: Sixty-four patients were
      randomized; 62% completed the 12-week trial and 37% completed the 52-week follow
      up. No between group differences were found in the percentages of heavy drinking
      and abstinent days. A significant reduction in levels of distress, depression and
      craving and improved HRQL occurred for both arms, whereas self-efficacy and
      social support remained unchanged in both groups. No adverse events were
      observed. CONCLUSIONS: Unlike previous positive trials in Italy, and similarly to
      a negative trial in the USA, we found no evidence of superiority of baclofen over
      placebo in the treatment of alcohol dependence. However, the high placebo
      response undermines the validity of this conclusion. Therefore, more placebo
      controlled trials are needed to either verify or discard a possible clinical
      efficacy of baclofen for alcohol dependence.

PMID- 25572708
TI  - Plastic plastids.

PMID- 25572707
TI  - Reproducibility of deep inspiration breath hold for prone left-sided whole breast
      irradiation.
AB  - BACKGROUND: Investigating reproducibility and instability of deep inspiration
      breath hold (DIBH) in the prone position to reduce heart dose for left-sided
      whole breast irradiation. METHODS: Thirty patients were included and underwent 2
      prone DIBH CT-scans during simulation. Overlap indices were calculated for the
      ipsilateral breast, heart and lungs to evaluate the anatomical reproducibility of
      the DIBH maneuver. The breathing motion of 21 patients treated with prone DIBH
      were registered using magnetic probes. These breathing curves were investigated
      to gain data on intra-fraction reproducibility and instability of the different
      DIBH cycles during treatment. RESULTS: Overlap index was 0.98 for the ipsilateral
      breast and 0.96 for heart and both lungs between the 2 prone DIBH-scans. The
      magnetic sensors reported population amplitudes of 2.8 +/- 1.3 mm for shallow
      breathing and 11.7 +/- 4.7 mm for DIBH, an intra-fraction standard deviation of
      1.0 +/- 0.4 mm for DIBH, an intra-breath hold instability of 1.0 +/- 0.6 mm and a
      treatment time of 300 +/- 69 s. CONCLUSION: Prone DIBH can be accurately
      clinically implemented with acceptable reproducibility and instability.

PMID- 25572709
TI  - PSHREG: a SAS macro for proportional and nonproportional subdistribution hazards
      regression.
AB  - We present a new SAS macro %pshreg that can be used to fit a proportional
      subdistribution hazards model for survival data subject to competing risks. Our
      macro first modifies the input data set appropriately and then applies SAS's
      standard Cox regression procedure, PROC PHREG, using weights and counting-process
      style of specifying survival times to the modified data set. The modified data
      set can also be used to estimate cumulative incidence curves for the event of
      interest. The application of PROC PHREG has several advantages, e.g., it directly
      enables the user to apply the Firth correction, which has been proposed as a
      solution to the problem of undefined (infinite) maximum likelihood estimates in
      Cox regression, frequently encountered in small sample analyses. Deviation from
      proportional subdistribution hazards can be detected by both inspecting
      Schoenfeld-type residuals and testing correlation of these residuals with time,
      or by including interactions of covariates with functions of time. We illustrate
      application of these extended methods for competing risk regression using our
      macro, which is freely available at:
      http://cemsiis.meduniwien.ac.at/en/kb/science-research/software/statistical
      software/pshreg, by means of analysis of a real chronic kidney disease study. We
      discuss differences in features and capabilities of %pshreg and the recent
      (January 2014) SAS PROC PHREG implementation of proportional subdistribution
      hazards modelling. 

PMID- 25572711
TI  - Global spectral deconvolution based on non-negative matrix factorization in GC *
      GC-HRTOFMS.
AB  - A global spectral deconvolution, based on non-negative matrix factorization (NMF)
      in comprehensive two-dimensional gas chromatography high-resolution time-of
      flight mass spectrometry, was developed. We evaluated the ability of various
      instrumental parameters and NMF settings to derive high-performance detection in
      nontarget screening using a sediment sample. To evaluate the performance of the
      process, a NIST library search was used to identify the deconvoluted spectra.
      Differences of the instrumental scan rates (25 and 50 Hz) in deconvolution were
      evaluated and results show that a high scan rate enhanced the number of compounds
      detected in the sediment sample. A higher mass resolution in the range of 1,000
      to 10,000 and a higher m/z precision in the deconvolution were needed to obtain
      an accurate mass database. After removal of multiple duplicate hits, which
      occurred in batch processes of NIST library search on the deconvolution result,
      62 unique assignable spectra with a match factor >=900 were obtained in the
      deconvoluted chromatogram from the sediment sample, including 54 spectra that
      were refined by the deconvolution. This method will help to detect and build up
      well-resolved reference spectra from various complex mixtures and will accelerate
      nontarget screening.

PMID- 25572710
TI  - Association between endothelin-1/endothelin receptor A and inflammation in mouse
      kidneys following acute ischemia/reperfusion.
AB  - Renal ischemia/reperfusion (I/R) is a common risk factor for renal failure.
      Expression of endothelin-1 (ET-1) and its receptor ETA were also reported to be
      involved in the development of acute and chronic renal disease. The present study
      was designed to investigate the association between inflammation and ET-1/ETA
      expression in mouse kidneys following acute I/R. The results demonstrated that
      acute renal I/R caused a significant increase in ET-1 and ETA gene and
      transcriptional levels compared with those of the sham group (P<0.01). Ischemia
      alone also resulted in a marked increase of ET-1 and ETA expression compared with
      that of the sham group (P<0.05). In addition, ET-1 and ETA expression was
      significantly increased in the I/R group compared with that of the ischemia group
      (P<0.05 or P<0.01). Of note, the altered expression levels of inflammatory
      cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in kidneys
      following I/R and ischemia alone were correlated with the expression of ET-1 and
      ETA. Hypoxia is the most important stimulus of I/R for tissue injury. In kidneys,
      ET-1 is primarily produced by renal glomerular endothelial cells (RGECs). In the
      present study, treatment with hypoxia alone or hypoxia/reoxygenation were found
      to increase ET-1 and ETA expression in human RGECs (P<0.05 or P<0.01). In order
      to elucidate the role of inflammation in the ischemia- and hypoxia-induced
      upregulation of ET-1 and ETA, human RGECs were exposed to different
      concentrations of TNF-alpha. As expected, TNF-alpha increased ET-1 and ETA
      expression in a dose-dependent manner; furthermore, application of the TNF-alpha
      inhibitor CAY10500 partially inhibited hypoxia-induced ET-1 and ETA expression.
      In conclusion, these results indicated that I/R induced upregulation of ET-1 and
      ETA in the kidneys, which was, at least in part, dependent on the production of
      inflammatory cytokines.

PMID- 25572712
TI  - Reduced expression of microRNA-206 regulates cell proliferation via cyclinD2 in
      gliomas.
AB  - MicroRNAs are short single-stranded non-coding RNA molecules that function as
      regulators of tumor progression, including regulation of glioblastoma multiforme,
      which is a World Health Organization grade IV glioma. Based on the results of a
      microRNA microarray, which included 198 patients with glioma from the Chinese
      Glioma Genome Atlas data set, it was observed that microRNA-206 (miR-206) was
      downregulated in high-grade (grades III and IV) gliomas compared with grade II
      gliomas. In addition, high expression of miR-206 was associated with longer
      overall survival time in glioma patients. The present study aimed to investigate
      the biological functions of miR-206 in glioma progression in vitro using the
      LN229 glioma cell line. Cell proliferation was observed to be inhibited
      subsequent to transfection with miR-206. It was suggested that miR-206 induced
      cell cycle G1/S phase arrest by suppressing the expression of cyclinD2. The
      results of the present study concluded that miR-206 inhibits glioma progression
      via the regulation of cyclinD2 and that miR-206 may be a novel biomarker with
      potential for use as a therapeutic target in gliomas.

PMID- 25572714
TI  - Nausea, vomiting and quality of life of patients with cancer undergoing
      antineoplastic treatment: an evaluation by pharmacists.
AB  - OBJECTIVE: This study aims to evaluate the frequency and severity of nausea and
      vomiting using two different instruments and relate them to quality of life (QOL)
      in patients with cancer receiving antineoplastic treatment. METHODS: Severity of
      chemotherapy-induced nausea and vomiting (CINV) was measured by Common
      Terminology Criteria for Adverse Events (CTCAE) and a numerical scale. QOL was
      assessed using the Functional Assessment of Cancer Therapy-General questionnaire.
      KEY FINDINGS: Of the 50 patients studied, 60.0% reported nausea (40.0% CTCAE
      grade 1; 66.7% moderate intensity on numerical scale) and 30.0% reported vomiting
      (46.7% CTCAE grades 1 and 2, each; 66.7% moderate intensity on numerical scale).
      CINV did not influence overall QOL. CONCLUSION: The frequency of CINV was high.
      There was no association between nausea/vomiting and overall QOL.

PMID- 25572713
TI  - Totally one-sided: painless unilateral proptosis.

PMID- 25572715
TI  - Permanent proteins in the urine of healthy humans during the Mars-500 experiment.
AB  - Urinary proteins serve as indicators of various conditions in human normal
      physiology and disease pathology. Using mass spectrometry proteome analysis, the
      permanent constituent of the urine was examined in the Mars-500 experiment (520
      days isolation of healthy volunteers in a terrestrial complex with an autonomous
      life support system). Seven permanent proteins with predominant distribution in
      the liver and blood plasma as well as extracellular localization were identified.
      Analysis of the overrepresentation of the molecular functions and biological
      processes based on Gene Ontology revealed that the functional association among
      these proteins was low. The results showed that the identified proteins may be
      independent markers of the various conditions and processes in healthy humans and
      that they can be used as standards in determination of the concentration of other
      proteins in the urine. 

PMID- 25572716
TI  - Interaction sorting method for molecular dynamics on multi-core SIMD CPU
      architecture.
AB  - Molecular dynamics (MD) is widely used in computational biology for studying
      binding mechanisms of molecules, molecular transport, conformational transitions,
      protein folding, etc. The method is computationally expensive; thus, the demand
      for the development of novel, much more efficient algorithms is still high.
      Therefore, the new algorithm designed in 2007 and called interaction sorting (IS)
      clearly attracted interest, as it outperformed the most efficient MD algorithms.
      In this work, a new IS modification is proposed which allows the algorithm to
      utilize SIMD processor instructions. This paper shows that the improvement
      provides an additional gain in performance, 9% to 45% in comparison to the
      original IS method. 

PMID- 25572717
TI  - Pantograph: A template-based method for genome-scale metabolic model
      reconstruction.
AB  - Genome-scale metabolic models are a powerful tool to study the inner workings of
      biological systems and to guide applications. The advent of cheap sequencing has
      brought the opportunity to create metabolic maps of biotechnologically
      interesting organisms. While this drives the development of new methods and
      automatic tools, network reconstruction remains a time-consuming process where
      extensive manual curation is required. This curation introduces specific
      knowledge about the modeled organism, either explicitly in the form of molecular
      processes, or indirectly in the form of annotations of the model elements.
      Paradoxically, this knowledge is usually lost when reconstruction of a different
      organism is started. We introduce the Pantograph method for metabolic model
      reconstruction. This method combines a template reaction knowledge base,
      orthology mappings between two organisms, and experimental phenotypic evidence,
      to build a genome-scale metabolic model for a target organism. Our method infers
      implicit knowledge from annotations in the template, and rewrites these
      inferences to include them in the resulting model of the target organism. The
      generated model is well suited for manual curation. Scripts for evaluating the
      model with respect to experimental data are automatically generated, to aid
      curators in iterative improvement. We present an implementation of the Pantograph
      method, as a toolbox for genome-scale model reconstruction, curation and
      validation. This open source package can be obtained from:
      http://pathtastic.gforge.inria.fr.

PMID- 25572718
TI  - Epoxy resin synthesis using low molecular weight lignin separated from various
      lignocellulosic materials.
AB  - A low molecular weight lignin from various lignocellulosic materials was used for
      the synthesis of bio-based epoxy resins. The lignin extracted with methanol from
      steam-exploded samples (steaming time of 5 min at steam pressure of 3.5 MPa) from
      different biomasses (i.e., cedar, eucalyptus, and bamboo) were functionalized by
      the reaction with epichlorohydrin, catalyzed by a water-soluble phase transfer
      catalyst tetramethylammonium chloride, which was further reacted with 30 wt%
      aqueous NaOH for ring closure using methyl ethyl ketone as a solvent. The
      glycidylated products of the lignin with good yields were cured to epoxy polymer
      networks with bio-based curing agents i.e., lignin itself and a commercial curing
      agent TD2131. Relatively good thermal properties of the bio-based epoxy network
      was obtained and thermal decomposition temperature at 5% weight loss (Td5) of
      cedar-derived epoxy resin was higher than that derived from eucalyptus and
      bamboo. The bio-based resin satisfies the stability requirement of epoxy resin
      applicable for electric circuit boards. The methanol-insoluble residues were
      enzymatically hydrolyzed to produce glucose. This study indicated that the
      biomass-derived methanol-soluble lignin may be a promising candidate to be used
      as a substitute for petroleum-based epoxy resin derived from bisphenol A, while
      insoluble residues may be processed to give a bioethanol precursor i.e., glucose.

PMID- 25572719
TI  - Improvement of antioxidant and moisture-preserving activities of Sargassum
      horneri polysaccharide enzymatic hydrolyzates.
AB  - In the previous study, we have found that polysaccharides isolated from Sargassum
      horneri exhibited bioactivities. The aim of this study was to investigate the
      antioxidant and moisture-preserving activities of molecular weight alteration of
      Sargassum horneri polysaccharide in vitro. For this purpose, the homogeneous
      active polysaccharide SHP was isolated from Sargassum horneri, and response
      surface methodology was employed to optimize the enzymatic degradation conditions
      to get SHP-derived fragments with different molecular weight. Results proved that
      the polysaccharide is capable of scavenging both ABTS and DPPH radicals in vitro.
      The study revealed that the polysaccharides had strong moisture-absorption and 
      retention capacities as compared to propanediol and glycerin. Furthermore, these
      data demonstrated that molecular weight had a certain effect on antioxidant
      activities and strong moisture-retention capacities of the polysaccharide from
      Sargassum horneri.

PMID- 25572720
TI  - A systematic evaluation of hydroxyethyl starch as a potential nanocarrier for
      parenteral drug delivery.
AB  - Development of parenteral nanoformulations is highly challenging due to the
      stringent demands on stability, reproducibility and high drug loading with
      minimal excipients. This study focuses on the development of a pharmaceutically
      acceptable nanomatrix system for parenteral delivery based on Hydroxyethyl Starch
      (HES), a FDA approved polymer that is relatively unexplored in drug delivery
      research. HES nanoparticles were prepared through a simple, two-step crosslinking
      precipitation route, yielding 160+/-5 nm, nearly monodispersed spherical
      particles with high colloidal stability. The utility of this nanocarrier for
      parenteral delivery was verified by a panel of hemo/cytocompatibility assays at
      high concentrations (0.05-1 mg/ml) in vitro and in vivo. HES nanomatrix was found
      effective in encapsulating two chemically distinct drugs having varying
      hydrophobicities, with the release behavior being influenced by their chemical
      nature and drug-matrix interactions. Better in vitro efficacy was measured for
      the nanoencapsulated drug than its bare form, establishing the potential of HES
      nanocarriers for controlled drug delivery.

PMID- 25572721
TI  - Purification and characterization of gamma poly glutamic acid from newly Bacillus
      licheniformis NRC20.
AB  - gamma-poly glutamic acid (gamma-PGA) has received considerable attention for
      pharmaceutical and biomedical applications. gamma-PGA from the newly isolate
      Bacillus licheniformis NRC20 was purified and characterized using diffusion
      distance agar plate, mass spectrometry and thin layer chromatography. All
      analysis indicated that gamma-PGA is a homopolymer composed of glutamic acid. Its
      molecular weight was determined to be 1266 kDa. It was composed of L- and D
      glutamic acid residues. An amplicon of 3050 represents the gamma-PGA-coding genes
      was obtained, sequenced and submitted in genbank database. Its amino acid
      sequence showed high similarity with that obtained from B. licheniformis strains.
      The bacterium NRC 20 was independent of L-glutamic acid but the polymer
      production enhanced when cultivated in medium containing L-glutamic acid as the
      sole nitrogen source. Finally we can conclude that gamma-PGA production from B.
      licheniformis NRC20 has many promised applications in medicine, industry and
      nanotechnology.

PMID- 25572722
TI  - Poisson-event-based analysis of cell proliferation.
AB  - A protocol for the assessment of cell proliferation dynamics is presented. This
      is based on the measurement of cell division events and their subsequent analysis
      using Poisson probability statistics. Detailed analysis of proliferation dynamics
      in heterogeneous populations requires single cell resolution within a time series
      analysis and so is technically demanding to implement. Here, we show that by
      focusing on the events during which cells undergo division rather than directly
      on the cells themselves a simplified image acquisition and analysis protocol can
      be followed, which maintains single cell resolution and reports on the key
      metrics of cell proliferation. The technique is demonstrated using a microscope
      with 1.3 MUm spatial resolution to track mitotic events within A549 and BEAS-2B
      cell lines, over a period of up to 48 h. Automated image processing of the bright
      field images using standard algorithms within the ImageJ software toolkit yielded
      87% accurate recording of the manually identified, temporal, and spatial
      positions of the mitotic event series. Analysis of the statistics of the
      interevent times (i.e., times between observed mitoses in a field of view) showed
      that cell division conformed to a nonhomogeneous Poisson process in which the
      rate of occurrence of mitotic events, lambda exponentially increased over time
      and provided values of the mean inter mitotic time of 21.1 +/- 1.2 hours for the
      A549 cells and 25.0 +/- 1.1 h for the BEAS-2B cells. Comparison of the mitotic
      event series for the BEAS-2B cell line to that predicted by random Poisson
      statistics indicated that temporal synchronisation of the cell division process
      was occurring within 70% of the population and that this could be increased to
      85% through serum starvation of the cell culture.

PMID- 25572723
TI  - Hip rotation angle is associated with frontal plane knee joint mechanics during
      running.
AB  - Inability to control lower extremity segments in the frontal and transverse
      planes resulting in large knee abduction angle and increased internal knee
      abduction impulse has been associated with patellofemoral pain (PFP). However,
      the influence of hip rotation angles on frontal plane knee joint kinematics and
      kinetics remains unclear. The purpose of this study was to explore how hip
      rotation angles are related to frontal plane knee joint kinematics and kinetics
      during running. Seventy runners participated in this study. Three-dimensional
      marker positions and ground reaction forces were recorded with an 8-camera motion
      analysis system and a force plate while subjects ran along a 25-m runway at a
      speed of 4m/s. Knee abduction, hip rotation and toe-out angles, frontal plane
      lever arm at the knee, internal knee abduction moment and impulse, ground
      reaction forces and the medio-lateral distance from the ankle joint center to the
      center of pressure (AJC-CoP) were quantified. The findings of this study indicate
      that greater hip external rotation angles were associated with greater toe-out
      angles, longer AJC-CoP distances, smaller internal knee abduction impulses with
      shorter frontal plane lever arms and greater knee abduction angles. Thus, there
      appears to exist a conflict between kinematic and kinetic risk factors of PFP,
      and hip external rotation angle may be a key factor to control frontal plane knee
      joint kinematics and kinetics. These results may help provide an appropriate
      manipulation and/or intervention on running style to reduce the risk of PFP.

PMID- 25572724
TI  - Dental and chronological age in children under oncological treatment.
AB  - The current oncology treatment has improved the survival of children with several
      types of cancer, and the effect of radiotherapy and/or chemotherapy treatment on
      dental maturation in comparison with chronological age is not widely known. The
      aim of this work was to evaluate and compare the impact of radiotherapy and/or
      chemotherapy treatment during dental maturation with chronological age in Chilean
      children diagnosed with cancer. Study Design was cross-sectional study on
      children diagnosed with different types of cancer and treated with radiotherapy
      and/or chemotherapy when they were ages of 0.1 to 13 years. Demirjian tables for
      both girls and boys are used to determine the dental age. The association between
      chronological and dental age was highly significant. Nevertheless, a linear
      relation between chronological and dental age was not observed when the data were
      stratified by BMI and type of treatment. This study confirmed that dental age is
      an indicator of chronological age but that other variables, such as body mass
      index, in children with cancer could be confounder variables. Thus, further
      studies are necessary to investigate the influence of BMI on tooth
      eruption/maturation in children under oncological treatment. 

PMID- 25572725
TI  - Italian survey on the use of anti-inflammatory drugs in osteoarthritis.
AB  - Osteoarthritis (OA) is the most common painful arthritic disease in adults,
      causes severe disability and worsens the quality of life of the patients. The aim
      of this survey, carried out on 147 Italian orthopedic doctors who attended an
      ISIAT (International Symposium Intra Articular Treatment) educational course in
      Barcelona, was to investigate some aspects of daily clinical practice in the
      management of OA: the most used pharmacological treatments, compliance to the
      most important Guidelines, the advantages of COXIBs in this setting and
      pharmacoeconomic aspects. The main results of this survey are: a) inflammation
      has become the main target in OA; b) Guidelines are a useful and valid tool for
      daily clinical practice; c) acetaminophen is no longer a valid therapeutical
      option for OA patients; d) anti-inflammatory drugs (NSAIDs and COXIBs) have a
      primary role in the management of OA, due to their dual activity (anti
      inflammatory and analgesic); e) selectivity of COXIBs for COX-2 is very
      important; f) within the COXIB class, the therapeutic value of etoricoxib has
      been widely recognized, especially in terms of safety and cost/benefit ratio. 

PMID- 25572726
TI  - Serine/Threonine phosphatases: classification, roles and pharmacological
      regulation.
AB  - Phosphatases are important enzymes in a variety of biochemical pathways in
      different cells which they catalyze opposing reactions of phosphorylation and
      dephosphorylation, which may modulate the function of crucial signaling proteins
      in different cells. This is an important mechanism in the regulation of
      intracellular signal transduction pathways in many cells. Phosphatases play a key
      role in regulating signal transduction. It is known that phosphatases are
      specific for cleavage of either serine-threonine or tyrosine phosphate groups. To
      date, numerous compounds have been identified. This paper reviews the
      classification, roles and pharmacological of protein serine/threonine phosphates.

PMID- 25572727
TI  - Vitiligo: symptoms, pathogenesis and treatment.
AB  - Vitiligo is an acquired cutaneous disorder of pigmentation, with an incidence of
      0.5&#x0025; to 2&#x0025; worldwide. There are three major hypotheses for the
      pathogenesis of vitiligo that are not exclusive of each other:
      biochemical/cytotoxic, neural and autoimmune. Recent data provide strong evidence
      supporting an autoimmune pathogenesis of vitiligo. As vitiligo can have a major
      effect on quality of life, treatment can be considered and should preferably
      begin early when then disease is active. Current treatment modalities are
      directed towards stopping progression of the disease and achieving
      repigmentation. Therapies include corticosteroids, topical immunomodulators,
      photo(chemo)therapy, surgery, combination therapies and depigmentation of
      normally pigmented skin. It seems that traditional Chinese medicine could be more
      effective than the current treatment for vitligo. 

PMID- 25572728
TI  - Current advances in the understanding and treatment of mevalonate kinase
      deficiency.
AB  - Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory
      metabolic disease that is caused by mutations in the MVK gene. Patients with MKD
      typically have an early onset in infancy. MKD is characterized by recurrent
      episodes of high fever, abdominal distress, diffuse joint pain, and skin rashes.
      In a subset of patients, MKD is also associated with elevated serum
      immunoglobulin D (IgD) levels (hyperimmunoglobulinemia D syndrome, HIDS). The
      clinical phenotype of MKD varies widely and depends on the severity of the
      impaired mevalonate kinase activity. Complete impairment results in the severe
      metabolic disease, mevalonic aciduria, while a partial deficiency results in a
      broad spectrum of clinical presentation, including HIDS. The precise molecular
      mechanisms behind the elevated serum IgD levels and inflammation that occurs in
      MKD remain unknown. Children who exhibit symptoms of MKD should be tested for
      mutations in the MKD gene. However, the complexity of MKD often results in delays
      in its definitive diagnosis and the outcome in adult age is not completely known.
      Therapeutic options for MKD are based on limited data and include non-steroidal
      anti-inflammatory drugs, corticosteroids, and biological agents that target
      specific cytokine pathways. In recent years, some studies have reported promising
      results for new biological drugs; however, these cases have failed to achieve
      satisfactory remission. Therefore, further studies are needed to understand the
      pathogenesis of MKD and identify innovative therapeutic tools for its management.

PMID- 25572729
TI  - Rhinosinusitis and asthma: a very long engagement.
AB  - Upper and lower airways may be considered as a unique entity, interested by
      coexisting inflammatory processes that share common etiopathogenic mechanisms.
      Previous studies have strongly demonstrated a relationship between rhinosinusitis
      and asthma. This has led to the introduction of the concept of ?United Airways?,
      which has also been included in the WHO document Allergic Rhinitis and its Impact
      on Asthma (ARIA); this concept has important consequences also on the treatment
      of these disorders. To better summarize the evident connection between upper and
      lower airway disease we decided to describe it as a multilayered construction,
      each level pointing out more deeply the relationship between these entities.

PMID- 25572730
TI  - Pathology of upper tract urothelial carcinoma with emphasis on staging.
AB  - Classification of upper tract urothelial preneoplastic and neoplastic lesions
      mirrors that of the urinary bladder, with all lesions of the bladder urothelium
      being possible in the upper tract and vice versa. There are three major groups of
      non-invasive urothelial neoplasms: flat, papillary, and inverted. These three
      groups share a similar morphological spectrum of intraurothelial changes, ranging
      from hyperplasia to dysplasia to carcinoma in situ. However, they differ in terms
      of architectural growth pattern compared to the surrounding non-neoplastic
      mucosal surface. Infiltrating urothelial carcinoma is defined as a urothelial
      tumor that invades beyond the basement membrane. Unlike in non-invasive papillary
      urothelial neoplasms (pTa), the role of histologic grade in pT1 and higher stage
      tumors has been suggested to be of only relative importance. The vast majority of
      tumors of the upper urinary tract are urothelial carcinoma. More commonly seen,
      however, are foci of squamous differentiation and, less frequently, glandular
      differentiation. Pure urothelial carcinomas also display a wide range of variant
      morphologies, and recognition of these morphologies is important for diagnosis,
      classification, and prognosis. 

PMID- 25572731
TI  - Role of mast cells in atherosclerosis: a classical inflammatory disease.
AB  - Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main
      risk factors for aging, hypertension and diabetes. Variance in plasma LDL
      cholesterol concentration may be associated with differences in cardiovascular
      disease risk and high levels of lipids are associated with increased risk of
      developing atherosclerosis. Macrophages, which generate pro-inflammatory
      cytokines, mainly interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF
      alpha), are deeply involved in atherosclerosis, as well as mast cells which
      generate several cytokines, including IL-6 and IFN-gamma, and chemokines such as
      eotaxin, MCP-1 and RANTES involved in monocyte recruitment and differentiation in
      the arterial wall. In addition, mast cells participate in lipid retention and
      vascular cell remodeling, and are mediators of innate and adaptive immunity
      during atherosclerosis. Mast cells which accumulate in the human arterial intima
      and adventitia during atherosclerotic plaque progression, release vasoactive and
      angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid
      metabolites, histamine, cytokines/chemokines, platelet activating factor (PAF)
      and proteolytic enzymes. Mast cells can be activated by pro-inflammatory stimuli,
      including cytokines, hypercholesterolemia, and hyperglycemia, and trigger the
      endothelial expression of adhesion molecules such as P-selection, vascular cell
      adhesion molecule-1 (VCAM-1) and chemokines which mediate the recruitment and
      adhesion of leukocytes. The participation of mast cells in atherosclerosis is
      still an enigma and it may be of therapeutic interest to clarify this process.

PMID- 25572732
TI  - Mgn-3/biobran enhances generation of cytotoxic CD8+ T cells via upregulation of
      dec-205 expression on dendritic cells.
AB  - Arabinoxylan rice bran (MGN-3/Biobran) has been shown to be a potent biological
      response modifier (BRM) that activates different arms of the immune system,
      including dendritic cells (DCs), which prime CD4+ helper T-cell responses. The
      present study explores the ability of MGN-3-activated DCs to prime CD8+ T cells
      and examines the mechanisms underlying its effect. Human monocyte-derived DCs
      were treated with MGN-3 (20 and 40 &#956;g/ml). Results indicate that treatment
      with MGN-3 caused DCs to prime higher granzyme B-expressing CD8+ T cells. Tumor
      lysate-pulsed MGN-3 DC also increased tumor cell killing compared to DC
      stimulated CD8+ T cells. This was associated with: i) increased expression of DEC
      205 in MGN-3-activated DCs in a dose-dependent manner; and ii) MGN-3 induced
      significant production of Type III interferon, IL29, but not Type I IFNs &#945;
      and &#946;. These results suggest that MGN-3 is a potent natural adjuvant that
      efficiently activates DCs and may therefore be useful for mounting an efficient
      immune response against infections and cancer. 

PMID- 25572733
TI  - Immunopathological and antimicrobial effect of black pepper, ginger and thyme
      extracts on experimental model of acute hematogenous pyelonephritis in albino
      rats.
AB  - Recent studies showed prominent antimicrobial activity of various plant extracts
      on certain pathogenic microorganisms, therefore we prepared crude aqueous
      extracts of black pepper, ginger and thyme and carried out an in vitro study by
      measuring antimicrobial activity of these extracts using the agar well diffusion
      method. An in vivo study was carried out on 50 adult healthy male albino rats
      which were divided into 5 groups, 10 rats each. Group 1: negative control group
      which received saline solution intragastrically daily; Group 2: Positive control
      group, injected with mixed bacterial suspension of S.aureus and E.coli as a model
      of pyelonephritis, then received saline solution intragastrically daily; Group 3:
      injected with the same dose of mixed bacterial suspension, then received 100
      mg/kg/day black pepper extract intragastrically; Group 4: injected with mixed
      bacterial suspension then received 500 mg/kg/day ginger extract intragastrically.
      Group 5: injected with mixed bacterial suspension then received 500 mg/kg/day
      thyme extract intragastrically. All groups were sacrificed after either 1 or 4
      weeks. Serum and blood samples were collected for lysozyme activity estimation
      using agarose lysoplate, measurement of nitric oxide production, and lymphocyte
      transformation test as well as for counting both total and differential
      leukocytes and erythrocytes. Kidney samples were tested histopathologically. Both
      in vivo and in vitro results confirm the efficacy of these extracts as natural
      antimicrobials and suggest the possibility of using them in treatment procedures.

PMID- 25572734
TI  - Clinical significance of hmgb1 expression in human gastric cancer.
AB  - High mobility group box 1 (HMGB1) has been proved to be implicated in a variety
      of cell physiological and pathological behaviors including immune response,
      inflammation and cancer. Accumulating evidence suggests that HMGB1 plays a
      critical role in the development and progression of multiple malignancies.
      However, the clinical significance and prognosis of HMGB1 expression in some
      cancers remain controversial. The present study aimed to investigate whether
      overexpression of HMGB1 is an independent prognostic factor in patients with
      gastric cancer. The correlation of HMGB1 expression with clinicopathologic
      characteristics and prognosis was assessed by immunohistochemical assay through
      tissue microarray procedure in 50 primary gastric cancer cases. Our results
      indicated that the positive expression of HMGB1 was significantly increased in
      the nucleus of gastric cancer tissues compared with the adjacent non-cancerous
      tissues (ANCT) (64.0&#x0025; vs 44.0&#x0025;, P=0.025), but was not linked to the
      clinicopathologic features, including the TNM stage (P=0.533) and metastatic
      lymph node (P=0.771), in patients with gastric cancer. Kapalan-Meier and log-rank
      analysis demonstrated that overexpression of HMGB1 did not exert significant
      impact on the overall survival of patients with gastric cancer (P=0.805).
      Furthermore, Cox regression analysis showed that high HMGB1 protein expression
      did not represent an independent risk factor for patients with gastric cancer
      (P=0.677). Taken together, our findings suggest that high expression of HMGB1 is
      not correlated with the clinicopathologic characteristics of gastric cancer, and
      cannot serve as an independent prognostic biomarker for patients with gastric
      cancer. 

PMID- 25572735
TI  - Blockade of the CXCR6 signaling inhibits growth and invasion of hepatocellular
      carcinoma cells through inhibition of the VEGF expression.
AB  - Chemokines have been shown to play a critical role in tumor development and
      progression. However, little is known about the function and molecular mechanisms
      of CXCR6 in multiple malignancies. In the present study, we aimed to investigate
      the role of CXCR6 in human hepatocellular carcinoma (HCC). The expression of
      CXCR6 was examined by immunohistochemical assay using a tissue microarray
      procedure. A loss-of-function experiment was performed to explore the effects of
      lentivirus-mediated CXCR6 shRNA (shCXCR6) on cell proliferation and invasive
      potential by MTT and Transwell assays in HCC cell line (SMMC-7721). It was found
      that the expression of CXCR6 protein was significantly increased in HCC tissues
      compared with that in adjacent non-cancerous tissues (ANCT) (63.04&#x0025; vs
      36.96&#x0025;, P=0.019), and correlated with the lymph-vascular space invasion in
      HCC patients (P=0.038). Knockdown of CXCR6 repressed cell proliferation and
      invasion of HCC cells followed by the down-regulation of vascular endothelial
      growth factor (VEGF). Taken together, our findings show that high expression of
      CXCR6 is positively associated with distant invasion of HCC patients, and
      blockade of CXCR6 signaling suppresses the growth and invasion of HCC cells
      through inhibition of the VEGF expression, suggesting that CXCR6 may represent a
      promising therapeutic target for the treatment of HCC. 

PMID- 25572736
TI  - The role of TLR4 and CD14 polymorphisms in the pathogenesis of respiratory
      syncytial virus bronchiolitis in greek infants.
AB  - Clinical manifestations of respiratory syncytial virus (RSV) infection vary from
      minimal disease to severe acute bronchiolitis. The structural complex of
      TLR4/CD14 participates in the virus recognition as a component of natural immune
      response. Genetic variations of TLR4/CD14 may explain great variations in disease
      severity. The aim of this study was to investigate the possible role of
      polymorphisms of TLR4, Asp299Gly and Thr399Ile and CD14, C-159T and C-550T in the
      development of RSV bronchiolitis. Our study included two groups of Greek infants
      and young children (A and B). Group A consisted of 50 infants <=2 years of age
      hospitalised with bronchiolitis and group B of 99 previously healthy children
      aged 4-14 years (control group) with a free past medical history. RSV was
      identified by PCR of genetic material that was extracted from nasopharyngeal
      samples collected from all patients. Blood samples were used to extract DNA and
      by using the PCR-RFLP method we performed TLR4 and CD14 genotyping. We found no
      association between TLR4 polymorphisms (Asp299Gly and Thr399Ile) and the
      development of acute bronchiolitis. For CD14 polymorphisms, a positive
      association was found between the C-159T and the development of bronchiolitis
      (p=0.05) but not for the other loci. There were no differences detected in the
      frequencies of the four polymorphisms studied among infants with RSV and non-RSV
      bronchiolitis. It is concluded that protein CD14 may have a functional role in
      the viral conjunction to the structural complex TLR4/CD14. The association
      between the polymorphism C-159T and the manifestation of disease found in our
      study points out that the severity in the development of acute bronchiolitis is
      not specified exclusively by the pathogen, but the immune response of the host
      also plays a significant role. More extensive multicentric studies need to take
      place, in order to lead to safer conclusions.

PMID- 25572738
TI  - "FoxP3 Hunting" during infection with Francisella tularensis.
AB  - Francisella tularensis is a Gram-negative intracellular bacterium that can cause
      acute disease in mouse models of infection when administered via the inhalational
      route. The immune response to a pulmonary infection is typified by an initial
      lack of pro-inflammatory cytokines, followed by hypercytokinemia prior to host
      death. It remains unclear what causes this delay in the host immune response. In
      this study we determine the presence of FoxP3 regulatory T cells in the lung,
      liver and spleen following intranasal infection with F. tularensis SCHU S4. In
      the lung, the site of initial infection, there is an increase in FoxP3+ cells
      during the first few days of infection and a notable absence of these cells at
      the point of cytokine storm and death (day 4 post-infection). This coincides with
      a decrease in the anti-inflammatory cytokine TGF-beta and increases of chemokines
      MIP-1alpha, MIP-1beta and RANTES. In our model, we also observed an overall
      decrease in the number of regulatory T cells in the spleen, which was not as
      evident in the liver. Overall, this data suggests that early on in an acute F.
      tularensis SCHUS4 infection regulatory T cells contribute to a dampening of the
      pro-inflammatory response, allowing for bacterial replication and spread.

PMID- 25572739
TI  - Management and treatment of anaphylaxis in children: still too low the rate of
      prescription and administration of intramuscular epinephrine.
AB  - Despite it being well known that anaphylaxis is a severe life-threatening
      reaction requiring prompt management and treatment, this entity is still under
      recognized and not correctly managed, above all in children. The aim of this
      study was to analyze the most frequent features of anaphylaxis in a pediatric
      population (n=65 patients) and to identify factors predicting more severe
      reactions. Among the 70 recorded episodes, food was the main culprit of
      anaphylaxis, and patients with a positive history for allergic asthma had more
      severe episodes (P=0.008). A self-injectable adrenaline was used only in 2 of the
      70 episodes and none of the 50 episodes managed in the Emergency Department was
      treated with intramuscular adrenaline. Only 10/65 patients (15&#x0025;) had a
      prescription for an auto-injector prior to the first episode of anaphylaxis. The
      retrospective analysis of the risk factors potentially requiring an epinephrine
      auto-injector prescription before the first anaphylactic episode, showed that of
      the 55 patients without prescription, at least 10 (18&#x0025;) should have been
      provided with a device, according to the most recent guidelines. In conclusion,
      notwithstanding intramuscular adrenaline being the first-line treatment of
      anaphylaxis, many episodes are still undertreated and the risk of anaphylaxis is
      still under-estimated. More efforts should be made to promote the correct
      management of anaphylaxis among both healthcare-providers and patients. 

PMID- 25572737
TI  - In silico modeling of the molecular interactions of antacid medication with the
      endothelium: novel therapeutic implications in head and neck carcinomas.
AB  - Pathological acid reflux is a common event in patients afflicted with head and
      neck squamous cell carcinomas (HNSCCs), known to play a role in HNSCC etiology
      and contribute to complications after surgery or during radiation and
      chemotherapy. Antacid medications are commonly prescribed in HNSCC patients as
      part of their cancer treatment, and consist of two classes: histamine 2 receptor
      antagonist class (H2RA, with cimetidine as its prototypical drug) and proton pump
      inhibitors class (PPI, with omeprazole as its prototypical drug). Clinical
      evidence revealed a significant survival benefit of antacid usage in a large
      cohort of HNSCC patients treated in our Otolaryngology Department, with a median
      follow-up of over 5 years. Therefore, we postulate that one mechanism by which
      antacid intake enhances patient survival could involve modulation of tumor cell
      adhesion to endothelium, critical in the initiation of the metastatic
      dissemination. This study investigates the potential physical interactions
      between cimetidine and omeprazole with the endothelial E-selection (E-sel) and
      its ligand sialyl Lewis X (sLe(x)) using a molecular visualization energy-based
      program (AutoDock). Docking results were further analyzed with the PyMOL program,
      which allowed for measurements of the distances between the drugs and the closest
      interacting atoms or residues on E-sel and sLe(x) molecules. Our model predicts
      that omeprazole displays a stronger interaction with E-sel than cimetidine, as
      extrapolated from the calculated overall binding energies. However, the shorter
      distances existing between interacting atoms in the proposed E-sel/cimetidine
      complex are suggestive of more stable interactions. Neither antacid/E-sel complex
      overcame the stronger Autodock-calculated sLe(x)/E-sel interaction, suggesting
      competitive inhibition was not involved. This study provides the first in silico
      evidence of omeprazole and cimetidine ability to bind to adhesion molecules
      involved in tumor dissemination, underlining their therapeutic potential in the
      HNSCC clinical management.

PMID- 25572740
TI  - In vitro action of sho-seiryu-to on allergen-exposed mononuclear cells.
AB  - Although Sho-seiryu-to (SST), used as a traditional herbal (Kampo) medicine
      mainly in China and Korea, is shown to have immunomodulating potential, such as
      an anti-allergic one, its underlying mechanism has not been completely clarified.
      To partially address the issue, we explored its effects on allergen-exposed
      mononuclear cells. Male balb/c mice were intraperitoneally administered ovalbumin
      (OVA: 20 &#956;g) plus alum or vehicle twice (Day 0 and Day 14). At Day 21, mice
      were sacrificed and splenocytes (mononuclear cells) were isolated and cultured in
      the presence or absence of OVA with or without SST. Thereafter, helper T-related
      cytokines in the culture supernatants were evaluated by means of ELISA. Protein
      level of interferon-&#947; was lower than 5.0 pg/mL in the supernatants from OVA?
      non-exposed or -exposed mononuclear cells in the presence or absence of OVA
      stimulation. On the other hand, SST induced the cytokine from both types of
      mononuclear cells in the presence (P < 0.05) or absence of OVA stimulation as
      compared to corresponding control. By contrast, interleukin (IL)-4 level tended
      to be decreased by SST in OVA-non-exposed mononuclear cells as did IL-13 in both
      non-exposed and exposed mononuclear cells as compared to vehicle. In conclusion,
      immunoregulating efficacy by SST on allergy-prone subjects may include, at least
      in part, restoring helper T balance mainly through hyperproduction of IFN-&#947;
      against mononuclear cells such as lymphocytes. 

PMID- 25572741
TI  - Angiomyolipoma of the helix without signs of systemic involvement: successful
      surgical approach.
AB  - Cutaneous angiomyolipoma (AMP) of the ear is an extremely rare benign mesenchymal
      tumour. Angiomyolipomas are the most common benign tumour of the kidney and could
      be associated in 20&#x0025; of the cases with the tuberous sclerosis complex
      (TBC), in which condition, most of the patients have several angiomyolipomas
      affecting both of the kidneys. We report the rare case of a 66-year-old female
      who had an asymptomatic, solitary, nodule on the helix of the right ear for
      several years, which was histologically assessed as angiomyolipoma. There were no
      clinical signs of the tuberous sclerosis complex (TBC) or renal AML. A surgical
      excision was performed with an excellent therapeutic result. In contrast to renal
      AMLs or PEComas, which are often invasive and may involve regional nodes,
      cutaneous AMLs are solitary, non-invasive, and not associated with tuberous
      sclerosis, and are curable by simple elliptical excision. 

PMID- 25572742
TI  - Probiotic bacteria lactobacillus and bifidobacterium attenuate inflammation in
      dextran sulfate sodium-induced experimental colitis in mice.
AB  - It is widely accepted that inflammatory Bowel disease (IBD) arises from a
      dysregulated mucosal immune response to the enteric microbiota in the gut of a
      genetically susceptible individual. No definitive therapies are available for
      this inflammatory disorder. Therefore it became imperative to develop new
      strategies for treating this disease. Probiotics have emerged as a potential new
      therapeutic strategy for IBD, however their exact mechanisms of action is still
      poorly defined. In this study, we address the potential effect of a probiotic
      cocktail (Ultrabiotique(r)) composed of four live bacterial strains (L.
      acidophilus, L. plantarum, B. lactis and B.breve) to promote recovery from acute
      colitis. Probiotic was given to mice by oral gavage after the onset of colitis
      and the establishment of dextran sulfate sodium (DSS)-induced intestinal injury.
      Clinical parameters were monitored daily, histological scores of colitis and the
      production of nitric oxide (NO) and interferon-&#947; (IFN-&#947;) were
      determined. In addition, TLR4, NF-&#954;B and iNOS colonic expression were
      examined. Probiotic treatment ameliorated clinical symptoms and histological
      scores. NO and IFN-&#947; production in plasma were decreased by probiotic. These
      results were associated with reduced TLR4, iNOS and NF-&#1082;B expression in
      colonic tissue. In conclusion, probiotic exerted anti-inflammatory effects and
      contributed to a rapid recovery of DSS-induced acute colitis. 

PMID- 25572743
TI  - Malignant melanoma of the conjunctiva ? successful surgical excision of the
      primary tumor and reconstruction by conjunctival auto transplantation from the
      contralateral eye.
AB  - Malignant melanoma of the conjunctiva is a rare tumor with incidence of 0.5
      cases/year per million population. It may also occur as de novo, as on the basis
      of preexisting melanocytic lesions (nevus or freckle) or most often from the so
      called primary acquired melanosis of the conjuctiva (PAM). It metastasizes mainly
      lymphogenic and hematogenous. The size of the primary tumor lesion,
      histopathological findings and absolute tumor thickness are essential for
      unfavorable prognosis. Conjunctival auto transplantation from the other eye is
      modern and innovative, but also a seldomly feasible method of reconstruction
      after conjunctival excision of tumors in this area. We present a rare case of a
      75-year-old patient with epithelioid cell malignant melanoma of the bulbar
      conjunctiva of the right eye, which de novo occurred, successfully treated by
      excision of the primary tumor and subsequent reconstruction by conjunctival auto
      transplant from the other eye. A very good therapeutic and aesthetic result was
      achieved. 

PMID- 25572745
TI  - Wrong melanoma thickness measurement: check it or leave it?
AB  - Cutaneous malignant melanoma (CMM) is one of the most aggressive forms of skin
      cancer, accounting for about 90% of deaths from cutaneous neoplasms, and its
      incidence has increased significantly in recent years. According to the 2012
      European criteria for diagnosis and treatment of malignant melanoma, diagnosis
      should be based on the combination of clinical features, dermoscopic data and
      histological examination, preferably after excisional biopsy. Tumour thickness
      and other parameters for local staging according to the AJCC classification
      should be included in the pathology report. Although many factors influence the
      prognosis and course of the disease, it has been established in a number of
      studies that tumour thickness is the most important parameter. Therapy of
      malignant melanoma in its initial stages mostly consists of wide local excision
      with 1 to 2 cm margins, and sentinel lymph node biopsy that is usually performed
      in cases of tumours with a thickness greater than 1 mm. We present the case of a
      58-year-old Bulgarian male with cutaneous superficial spreading malignant
      melanoma, in which, after complete excision, histological examination established
      an inaccurate tumour thickness (0.7 mm), with consequent inadequate staging and
      further management. After reassessment of the results in another institution (as
      well as their confirmation by two additional independent histopathology
      laboratories in our country ? 1.92 mm), in the National Oncological Hospital
      where the patient was initially evaluated, sentinel lymph node biopsy was not
      performed, contrary to the generally accepted European and World standards. With
      the present case we raise some current issues regarding diagnosis and therapy of
      Bulgarian patients (not only in the case presented) with malignant melanoma in
      the 21st century, and discuss the urgent need for external quality control
      procedures and standardization of the histopathologic reporting, which is of
      paramount importance in the staging and subsequent management of these patients.

PMID- 25572744
TI  - Association of the IRF5 SNP rs2004640 with systemic sclerosis in Han Chinese.
AB  - Systemic sclerosis (SSc) is a complex disease involving multiple genetic factors.
      An association of the IRF5 polymorphism with SSc was reported in Caucasian
      populations of Europe and North America, as well as in Japanese populations. The
      present study aimed to examine whether the SSc-associated SNP rs2004640 of IRF5
      gene confer susceptibility to SSc and clinical features of SSc in a Han Chinese
      population. A Han Chinese cohort consisting of 424 SSc patients and 502 healthy
      controls were examined in the study. TaqMan assays were carried out to examine
      the SNP. Exact p-values were obtained (Fisher?s test) from 2x2 tables of allele
      counts and disease status. SSc patients of Han Chinese showed increased
      homozygous TT genotype of the rs2004640 (p = 0.027, odds ratio (OR) = 1.4, CI
      =1.03-1.93), which was significantly associated with pulmonary fibrosis of SSc
      and ATA-positive SSc of Han Chinese. The lcSSc and ACA-positive SSc of Han
      Chinese appeared also in association with the increased T allele frequency.
      However, the Chinese dcSSc did not show any association with the rs2004640. The
      results were consistent with previous reports in other ethnic populations in
      supporting the notion that polymorphisms of IRF5 may play an important role in
      susceptibility to SSc. 

PMID- 25572746
TI  - Subclinical carotid atherosclerosis in elderly patients with primary Sjogren
      syndrome: a duplex Doppler sonographic study.
AB  - A growing body of evidence presents a link between chronic inflammatory rheumatic
      diseases and atherosclerosis. To evaluate subclinical carotid atherosclerosis in
      an elderly group of patients with primary Sjogren syndrome compared with a
      control group matched for age, sex, ethnicity and cardiovascular risk factors, we
      enrolled 18 patients with Primary Sjogren Syndrome (mean age 65 +/- 5.93 SD) and
      18 mild Ostheoarthritic patients (mean age 66 +/- 5.94 SD) from the outpatient
      department of Rheumatology, University ?Campus Bio-Medico, Rome, Italy, matched
      for age, sex, ethnicity and cardiovascular risk factors. A duplex Doppler
      sonographic study of carotids was performed in order to evaluate intima-media
      thickness (IMT), stiffness and haemodynamic parameters [resistivity and
      pulsatility indices (RI and PI, respectively)]. No significant difference was
      found between primary Sjogren syndrome and control patients in IMT, stiffness and
      haemodynamic parameters. The lack of significant difference in subclinical
      atherosclerosis between elderly primary Sjogren syndrome and control matched
      patients, indicates that traditional cardiovascular risk factors, immunologic
      alterations and chronic inflammation do not influence the progression of vascular
      damage in the carotid circulation of patients with median disease duration of 6.5
      years.

PMID- 25572747
TI  - Bradykinin B2 receptor antagonist off label use in short-term prophylaxis in
      hereditary angioedema.
AB  - Hereditary angioedema type I (HAE-C1-INH) is an inherited disorder characterized
      by repeated severe angioedema attacks mostly triggered by traumas, emotional
      stress, increased estrogen levels or surgical procedures, in particular,
      odontostomatological interventions. Icatibant, a bradykinin B2 receptor
      antagonist, has been approved for treatment of HAE attacks. In this paper we
      describe the ?off label? administration of icatibant as short-term prophylaxis of
      dental extraction in a patient with HAE with the aim of preventing perioperative
      angioedema attacks. The drug showed an effective and safe profile. Thus, a short
      term prophylaxis of angioedema attacks in patients with HAE may be arranged on a
      multidisciplinary basis, according to the clinical history of each single
      patients. 

PMID- 25572748
TI  - Routine use of a protease zymogen-based colorimetric assay for the detection of
      Beta-glucan and its role in clinical practice.
AB  - The detection of Aspergillus antigen (galactomannan) is considered a reliable
      marker for the diagnosis of invasive aspergillosis (IA), yet the sensibility and
      specificity of the assays commonly employed in routine are not optimal. The aim
      of the present study was to investigate whether the detection of another
      panfungal antigen, the (1,3)-b-D-glucan could have an auxiliary role in the
      identification of patients with IA. The study was carried out on 63 sera
      belonging to patients who had been screened for galactomannan, according to the
      clinical suspect of IA. Our data show that the positive galactomannan results
      were not confirmed by positive (1,3)-b-D-glucan results in patients receiving
      therapy with beta-lactam antibiotics associated with tazobactam, whereas in all
      the other cases, with the exception of four, the results of the (1,3)-b-D-glucan
      test were confirmatory of the galactomannan results. 

PMID- 25572749
TI  - Severe septal panniculitis in a multiple sclerosis patient treated with
      interferon-beta.
AB  - We report a memorable case of severe septal panniculitis in an MS patient
      following the subcutaneous administration of interferon beta-1b, manifesting as a
      painful, indurated, erythematous lesion of the thigh, which appeared at the
      injection site. 

PMID- 25572750
TI  - Effect of betamethasone in combination with antibiotics on gram positive and gram
      negative bacteria.
AB  - Betamethasone is an anti-inflammatory steroid drug used in cases of anaphylactic
      and allergic reactions, of Alzheimer and Addison diseases and in soft tissue
      injuries. It modulates gene expression for anti-inflammatory activity suppressing
      the immune system response. This latter effect might decrease the effectiveness
      of immune system response against microbial infections. Corticosteroids, in fact,
      mask some symptoms of infection and during their use superimposed infections may
      occur. Thus, the use of glucocorticoids in patients with sepsis remains extremely
      controversial. In this study we analyzed the in vitro effect of a commercial
      formulation of betamethasone (Bentelan) on several Gram positive and Gram
      negative bacteria of clinical relevance. It was found to be an inhibitor of the
      growth of most of the strains examined. Also the effect of betamethasone in
      combination with some classes of antibiotics was evaluated. Antibiotic-steroid
      combination therapy is, in such cases, superior to antibiotic-alone treatment to
      impair bacterial growths. Such effect was essentially not at all observable on
      Staphylococcus aureus or Coagulase Negative Staphylococci (CoNS). 

PMID- 25572751
TI  - Nasal cytological assessment after crenotherapy in the treatment of chronic
      rhinosinusitis in the elderly.
AB  - Chronic rhinosinusitis (CRS) determines irreversible alterations of the nasal
      mucosa with consequent impairment of ciliary movements and, therefore,
      mucociliary clearance (MCC). People of all ages can be affected by CRS but the
      elderly are subjects at the highest risk. CRS in the elderly with an age-related
      physiological impairment of nasal respiratory function, often accompanied by
      other chronic diseases, requires additional therapies to be added to the numerous
      daily medications. Since the currently available therapies for CRS include the
      use of drugs that can have adverse effects and contraindications, crenotherapy
      could represent a therapeutic option. Indeed, because the adverse effects and
      contraindications of crenotherapy are scarce, it can be safely used in elderly
      patients with comorbidities. The aim of this study is to evaluate the nasal
      cytological assessment after crenotherapy in elderly subjects with CRS. Two
      groups, comprising a total of 84 elderly subjects with CRS, were treated with
      crenotherapy with sodium chloride sulphate hyperthermal water rich in mineral
      salts (group I, n=49) and saline solution (group II n=35). Cytological assessment
      for both groups took place at baseline (T0) and 1 month after treatment (T30). At
      T30 the nasal cytological assessment showed statistically significant
      improvements in the ciliary motility and in the count of neutrophils and spores
      in group I, but not in group II. Conversely, there were no significant
      differences in the count of eosinophils, mast cells, bacteria and biofilm in
      either group. Our data for the first time focused on the role of crenotherapy in
      the improvement of cytological assessment of CRS in the elderly. 

PMID- 25572752
TI  - Effects of glucosamine and nucleotide association on fibroblast: extracellular
      matrix gene expression.
AB  - Glucosamine (Gluc) is a drug used as an anti-inflammatory in moderate forms of
      knee arthrosis. A further off label use of Gluc is in the anti-aging treatments
      associated with Polideoxirybonucleotide (PDRN) through intra-dermal injection for
      a procedure called bio-stimulation. An unexpected effect on cultured dermal
      fibroblasts, during an experimental study on the gene activation in aesthetic bio
      stimulation, was observed. The results have potential application in orthopaedic
      medical therapy. Fibroblast primary cultures were carried out, seeding cells on a
      layer of Gluc or PDRN alone or in combination for 24 h. Real Time-PCR was
      performed to investigate several gene expressions. The MMP13 and the IGF-I gene
      expression in fibroblast cultures were strongly inhibited after 24 h of
      incubation with the association of Gluc and PDRN, whereas Gluc and PDRN alone
      produced a modest inhibition of IGF-I and an activation of MMP13. MMP13 is
      present in osteoarthritic cartilage and this enzyme plays a significant role in
      cartilage collagen degradation. IGF1 is involved in growth and development and is
      successfully used in tissue-engineering for cartilage repair. Based on the
      reported data, we infer that the association of Gluc and PDRN has a potential
      application in cartilage therapy. Additional basic science and clinical studies
      are needed to confirm this preliminary report. 

PMID- 25572753
TI  - Frequency and clinical implications of the isolation of rare nontuberculous
      mycobacteria.
AB  - BACKGROUND: To date, more than 125 species of nontuberculous mycobacteria (NTM)
      have been identified. In this study, we investigated the frequency and clinical
      implication of the rarely isolated NTM from respiratory specimens. METHODS:
      Patients with NTM isolated from their respiratory specimens between July 1, 2010
      and June 31, 2012 were screened for inclusion. Rare NTM were defined as those NTM
      not falling within the group of eight NTM species commonly identified at our
      institution: Mycobacterium avium, M. intracellulare, M. abscessus, M.
      massiliense, M. fortuitum, M. kansasii, M. gordonae, and M. peregrinum. Clinical,
      radiographic and microbiological data from patients with rare NTM were reviewed
      and analyzed. RESULTS: During the study period, 73 rare NTM were isolated from
      the respiratory specimens of 68 patients. Among these, M. conceptionense was the
      most common (nine patients, 12.3%). The median age of the 68 patients with rare
      NTM was 68 years, while 39 of the patients were male. Rare NTM were isolated only
      once in majority of patient (64 patients, 94.1%). Among the four patients from
      whom rare NTM were isolated two or more times, only two showed radiographic
      aggravation caused by rare NTM during the follow-up period. CONCLUSIONS: Most of
      the rarely identified NTM species were isolated from respiratory specimens only
      once per patient, without concomitant clinical aggravation. Clinicians could
      therefore observe such patients closely without invasive work-ups or treatment,
      provided the patients do not have decreased host immunity towards mycobacteria.

PMID- 25572755
TI  - An exploration of what service users value about early intervention in psychosis
      services.
AB  - OBJECTIVE: Given the potential severity of developing chronic mental health
      problems, particular attention has been paid to the first emergence of psychosis.
      Earlier detection is expected to lead to quicker access to the effective
      treatment that is necessary during the 'critical period' and is one of the main
      incentives for setting up early intervention in psychosis (EIP) services. EIP
      services have demonstrated good clinical outcomes since inception, but little is
      understood yet as to which specific element of EIP leads to these good outcomes.
      The aim of this research was to conduct an exploratory investigation of the
      elements that people experiencing a first episode of psychosis find most valuable
      about EIP treatment. DESIGN: The study employed a single group design and
      utilized Q-methodology. METHOD: 20 people with first-episode psychosis aged
      between 18 and 35 were recruited and asked what they valued most about EIP.
      RESULTS: Four separate factors were identified, which were interpreted and named
      as 'therapeutic relationship', 'medical care', 'psychological interventions', and
      'support, coping and recovery'. Three of the factors were consistent with a
      biopsychosocial approach of EIP that is recommended by expert professionals
      working in EIP services and Government guidance on service delivery. CONCLUSIONS:
      The factor that accounted for the most variance is 'therapeutic relationship',
      highlighting the importance of non-specific factors in mental health care and
      recovery from a first episode of psychosis. PRACTITIONER POINTS: Service users
      reported that four main components of Early Intervention in Psychosis Services
      were helpful to them. These included a strong and effective therapeutic
      relationship, as well as medication, psychological therapies, and practical help
      and support. Services are valued both for the quality of the therapeutic
      relationship but also for their ability to deliver meaningful and valued
      treatments in this context.

PMID- 25572757
TI  - Visceral Adiposity Index and pattern of dyslipidaemia at different stages of
      glucose intolerance-A study from India.
AB  - AIM: To see the pattern of dyslipidaemia and Visceral Adiposity Index (VAI) at
      different stages of glucose intolerance in Indian population. METHODS: Data of
      600 subjects were considered for this analysis. Waist circumference and BMI were
      recorded. OGTT and lipid profile were done. Subjects were divided into three
      groups; Group 1 (Normoglycaemic), Group 2 (Prediabetes) and Group 3 (new DM).
      Subjects having one or more lipid parameters outside the targets recommended by
      ADA were considered to have dyslipidaemia. VAI, a sex-specific index, was
      calculated. RESULTS: LDL-C was the most common isolated single abnormality
      (84.5%), followed by HDL-C (58.7%) and triglycerides (49.7%) among the total
      subjects. 73% had high LDL-C and 56% had low HDL-C even in normoglycaemic
      subjects. LDL-C abnormality was similar in prediabetes and diabetes. Commonest
      combination of two abnormalities was seen mainly with LDL-C and HDL-C. Mean VAI
      increased at different stages of glucose intolerance and VAI>=2.3 gave
      sensitivity of 61.2% and specificity of 59.7% to detect glucose intolerance.
      CONCLUSIONS: The most common single lipid abnormality was high LDL-C. Combination
      of two abnormalities was seen with LDL-C and HDL-C. VAI increased at different
      stages of glucose intolerance. These findings may be useful for targeting high
      risk population.

PMID- 25572756
TI  - Waiting with bated breath: opportunistic orientation to human odor in the malaria
      mosquito, Anopheles gambiae, is modulated by minute changes in carbon dioxide
      concentration.
AB  - Females of the malaria mosquito, Anopheles gambiae, predominantly obtain blood
      meals within human dwellings. Being highly anthropophilic, human skin odor offers
      a reliable, host-specific cue, but the challenge posed by pervasive human odor
      found indoors from used clothing, bedding etc. remains unclear. Anopheles gambiae
      spends much of its adult life indoors, constantly exposed to human odor even when
      dwellings are unoccupied. In landing assays, we found that female mosquitoes
      respond very weakly to human skin odor alone, suggesting that, alone, it is an
      ineffective landing cue. Landing, however, was dramatically increased by addition
      of carbon dioxide at a range of concentrations above ambient. Indeed, this effect
      was seen even when carbon dioxide was just 0.015% above ambient within the assay
      cage. The synergistic effect of added carbon dioxide quickly waned, thereby
      facilitating a highly adaptive "sit-and-wait" ambush strategy, wherein females
      ignore persistent human odor until a living human is present. Unexpectedly,
      landing rates in the presence of added carbon dioxide were almost as robust
      during daytime, when An. gambiae has previously been assumed inactive, possibly
      facilitating opportunistic feeding at times of day when human dwellings are
      occupied intermittently. We suggest earlier studies that showed strong upwind
      flight behavior toward human odor alone could, in fact, have been demonstrating
      orientation toward a human dwelling rather than toward a living human. This new
      interpretation of how human odors mediate upwind orientation and landing in An.
      gambiae is discussed.

PMID- 25572759
TI  - Presence and association of sub clinical hypothyroidism in subjects with
      metabolic syndrome.
AB  - AIMS: To determine the prevalence of subclinical hypothyroidism (SCH) among
      subjects with metabolic syndrome and to find out the relationship of subclinical
      hypothyroidism with different components of metabolic syndrome. MATERIALS AND
      METHODS: The study was conducted in the Department of Endocrinology, Bangladesh
      Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic
      Disorders (BIRDEM), Dhaka during the period of April 2008-March 2009. One hundred
      and seventy three subjects with metabolic syndrome (according to IDF criteria)
      aged 20-69 years were included in the study. After primary selection, FPG and
      lipid profile were done. Those who had FPG>=100mg/dl or dislipidemia were
      selected for routine investigations such as SGPT, S. creatinine, TC, DC, ESR,
      HB%, ECG, and Ultrasonography of whole abdomen to exclude liver disease, renal
      disease, acute illness and cardiac disease respectively. Patients having normal
      investigations were finally selected for serum level of FT4 and TSH. RESULTS: A
      total of 173 subjects (105 male, and 68 female,) with metabolic syndrome were
      studied. Among them 14.3% (n=15) of male and 19.1% (n=13) of female had SCH. SCH
      was found more in obese subjects (BMI>=25kg/m(2) vs. BMI<25kg/m(2)). There was no
      significant difference among different parameters of metabolic syndrome in
      subjects with or without SCH. Although SCH was more prevalent in those who had
      hypertrigyceridemia and hypertension, there was no association between presence
      of fatty liver and SCH. CONCLUSIONS: Among the study subjects 14.3% male and
      19.1% female had SCH. SCH is more prevalent in 41-60 years age group. No
      significant association was found among different parameters of MetS with SCH,
      however, when they constitute metabolic syndrome; there was a significant
      association between MetS and SCH.

PMID- 25572758
TI  - Association of fructosamine to indices of dyslipidemia in older adults with type
      2 diabetes.
AB  - AIMS: To evaluate the association of serum fructosamine values to lipid profiles
      and to other indices of glycemia both at baseline and over time in adults with
      type 2 diabetes (T2DM). METHODS: Forty adults aged 45 or older with T2DM, not
      taking insulin, and an HbA1c of 6-10% were enrolled in a randomized controlled
      trial regarding the effects of an 8-week yoga program on glycemia and related
      cardiovascular disease risk indices in adults with T2DM. Fasting blood was drawn
      to assess glycemia (HbA1c, glucose, and fructosamine) and dyslipidemia (LDL, HDL,
      total cholesterol, cholesterol:HDL ratio, LDL:HDL ratio, and triglycerides) pre
      and post-intervention. Because the relation of fructosamine to other indices of
      glycemia and to lipid profiles did not differ between treatment groups either at
      baseline or over time, groups were pooled for analysis. RESULTS: Baseline
      fructosamine values were significantly correlated with HbA1c (r=0.77, P<0.0001),
      glucose (r=0.72, P<0.0001), LDL:HDL ratio (r=0.46, P=0.01), cholesterol:HDL ratio
      (r=0.55, P=0.002), and triglycerides (r=0.39, P=0.032), but not to other lipid
      indices at baseline. Change in fructosamine over 8 weeks was significantly
      correlated with change in HbA1c (r=0.63, P=0.0001), glucose (r=0.39, P=0.029),
      cholesterol (r=0.65, P<0.0001), LDL (r=0.55, P=0.001), LDL:HDL ratio (r=0.53,
      P=0.003), and cholesterol:HDL ratio (r=0.52, P=0.002), and was more strongly
      related to change in lipid values than were other indices of glycemia.
      CONCLUSIONS: Fructosamine was significantly correlated with measures of
      dyslipidemia and glycemia both at baseline and over time, and may represent a
      relatively sensitive and low cost index of short to medium term change in both
      glycemia and certain lipid profiles. However, findings from this small pilot
      study should be interpreted with caution, and warrant replication in larger
      prospective studies.

PMID- 25572760
TI  - Serum insulin is significantly related to components of the metabolic syndrome in
      Japanese working women.
AB  - BACKGROUND: The aim of this study was to examine the association between serum
      insulin levels and components of the metabolic syndrome (MetS) in working women.
      METHODS: The target subjects were 141 working women. Serum triglyceride, HDL
      cholesterol, uric acid, plasma insulin and plasma glucose were measured in
      addition to waist circumference and blood pressure. RESULTS: MetS was diagnosed
      based on the modified criteria of the International Diabetes Federation, and was
      present in 7.1% (10/141) of the study subjects. Stepwise multiple regression
      analysis showed that some components of MetS were significantly associated with
      log-transformed values of the serum insulin. The standardized regression
      coefficient for the waist circumference, high density lipoprotein cholesterol,
      systolic blood pressure and age were 0.238, -0.333, 0.309 and -0.156,
      respectively. CONCLUSIONS: A statistically significant relationship existed
      between the components of MetS and the serum insulin levels in working women.

PMID- 25572761
TI  - NO levels in diabetes mellitus: Effects of l-NAME and insulin on LCAT, Na(+)/K(+)
      ATPase activity and lipid profile.
AB  - OBJECTIVES: Diabetes mellitus (DM) is a chronic disease and one of the most
      important health problems. Several factors may be responsible for the
      complications of diabetes mellitus including alterations in the activities of
      sodium-potassium adenosine triphosphatase (Na(+)/K(+) ATPase) and
      lecithin:cholesterol acyltransferase (LCAT) and also levels of nitric oxide (NO).
      We have investigated the effects of alterations in serum NO levels on activities
      of erythrocyte membran Na/K ATPase and serum LCAT enzymes. MATERIALS AND METHODS:
      The experiments were performed on male rats divided into four groups: group 1,
      control (standart diet); group 2, diabetic control (single dose of 65mg/kg of
      streptozotocin (STZ), i.p); group 3, STZ+insulin (8IU/kg/day s.c.); group 4
      (STZ+l-NAME 5mg/kg/day orally). RESULT: Streptozotocin-induced diabetic rats,
      showed a significant increase in blood glucose and serum cholesterol (C) and
      triglyceride (TG). Compared to the control group with diabetic group plasma LCAT
      concentrations and erythrocyte membrane Na(+)/K(+) ATPase were found to be
      decreased. Activities of Na(+)/K(+) ATPase and serum NO level were decreased with
      the administration of l-NAME. We observed that insulin was ameliorated in all
      parameters. CONCLUSIONS: Serum NO levels is related to erythrocyte membrane
      Na(+)/K(+) ATPase activity. But serum NO levels did not affect the plasma LCAT
      activity and serum lipid profiles.

PMID- 25572762
TI  - Risk factors of diabetic retinopathy in Bangladeshi type 2 diabetic patients.
AB  - AIMS: To determine the risk factors associated with diabetic retinopathy (DR) in
      Bangladeshi type 2 diabetic subjects. METHODS: A cohort of 977 type-2 diabetic
      patients was recruited retrospectively based on hospital records in 2008, who
      were naive type-2 diabetes during 1993. Data on diabetes and lipid profile with
      serum creatinine and biophysical measures were obtained at baseline, 5, 10 and 15
      years. DR was diagnosed by retinal color photography. Generalized linear models
      were used to assess the associations of clinical, biochemical and anthropometric
      variables with retinopathy at three follow-up. Cumulative exposures were
      determined based on average exposure to individual attribute. IRR and 95% CI were
      generated through Poisson regression model, adjusting for age-at-diagnosis of
      diabetes, baseline BMI, end-line waist-to-hip ratio and present physical activity
      status. RESULTS: DR patients had significantly poorer glycemic control at all
      three follow-ups. Age, residence, physical activity, serum creatinine and
      hypertension appeared as independent risk factors for DR in all three follow-up
      points. Poisson regression model identified glucose deregulation (IRR 1.8; CI 1.5
      2.1), hypertension (IRR 1.5; CI 1.2-1.8) and raised serum creatinine (IRR 1.9; CI
      1.5-2.3) as significant predictors for DR adjusted for possible confounders. Work
      related moderate-to-heavy physical activity (IRR 0.2; CI 0.1-0.3) appeared as
      protective. CONCLUSIONS: Along with poor glycemic control, hypertension,
      nephropathy are independent risk factor retinopathy.

PMID- 25572763
TI  - Metabolic syndrome in first degree relatives of patients with type 2 diabetes:
      Incidence and risk factors.
AB  - AIMS: First degree relatives (FDRs) of people with type 2 diabetes are at greater
      cardiovascular and diabetes risk. It is not known whether they are also at
      greater risk of metabolic syndrome (MetS). The objectives of present study were
      to assess the incidence of and risk factors for the development of MetS in FDRs
      of patients with type 2 diabetes. METHODS: A total of 3217 (842 men and 2375
      women) FDRs of consecutive patients with type 2 diabetes aged 30-70 years in 2003
      2005 were followed through 2010. At baseline participants underwent a standard
      75g 2-h standard OGTT and HbA1c measurements. MetS was defined by the NCEP-ATP
      III. The study group consisted of 734 participants without MetS and history of
      known diabetes at baseline and had at least one subsequent review in mean (SD)
      follow-up period of 5.5 (1.2) years. RESULTS: The prevalence of MetS was 35.8%
      (95% CI: 34.2, 37.5). The incidence of MetS was 4.3% (95% CI: 3.7, 4.9) (4.6% men
      and 4.2% women) per year. Multivariate analysis revealed that impaired glucose
      tolerance (IGT) (RR 1.89 (95% CI: 1.28, 2.79)), impaired fasting glucose (IFG)
      (RR 1.39 (95% CI: 1.10, 1.73)) and lower HDL (RR 1.34 (95% CI: 1.12, 1.60)) were
      associated with MetS. CONCLUSIONS: The findings of this study illustrate for the
      first time the incidence of MetS in FDRs of patients with type 2 diabetes in
      Iran. Risk of MetS may increases with IGT, IFG and lower HDL.

PMID- 25572764
TI  - The metabolic syndrome in type 2 diabetic patients in Gorgan: According to NCEP
      ATPIII and IDF definitions.
AB  - AIMS: People with metabolic syndrome are at increased risk for developing
      diabetes mellitus and cardiovascular disease. The present study aimed to assess
      the metabolic syndrome in type 2 diabetes and compare them with two used methods
      of diagnostic criteria in Gorgan. METHODS: The study group included 293 type 2
      diabetic patients whom referred to the Department of Diabetes Center in Golestan
      University of Medical Sciences (2011). The metabolic syndrome was determined
      according to ATPIII and IDF definitions. RESULTS: According to ATPIII and IDF
      criteria, the frequency of metabolic syndrome was 75.42% and 76.79%,
      respectively. According to ATPIII, the mean triglycerides, body mass index,
      systolic blood pressure and diastolic blood pressure were higher in subjects with
      metabolic syndrome than subjects without metabolic syndrome. According to IDF,
      the mean triglycerides, body mass index and males' waist circumferences were
      higher in subjects with metabolic syndrome. CONCLUSIONS: This study showed that
      females were more affected than males. This may be due to the specific
      characteristics in the lifestyle changes between females and males diabetic
      patients among Gorgan inhabitants. Females are less educated in comparison with
      males diabetic. The majority of females with metabolic syndrome were householder.
      It seems that they do less physical activity at home. In conclusion, it appears
      that the female need to change their life style in this area to halt the burden
      of cardiovascular complications in diabetic patients.

PMID- 25572765
TI  - Critical appraisal of the recent data published on the link between insulin and
      cancer.
AB  - Recent publications indicate a possible association between newer analogue
      insulin Glargine and cancer. However all these data were observational in nature
      and subject to lot of methodological errors. It is practically impossible to
      derive at a cause and effect relationship based on these observational studies.
      There are several confounding factors like hyperinsulinemia, obesity and smoking,
      which independently can be associated with cancer risk. This review looks into
      the recently published observational studies from the methodological point of
      view and whether such a negative association can indeed be drawn as a conclusion.
      Several methodological defects were identified in the process of scrutiny and we
      concluded it is not possible to conclude that there is an association between
      Glargine use and cancer. However long-term prospective data is required to come
      to definite conclusion. 

PMID- 25572766
TI  - Point of care testing for pediatric following up of hemoglobin A1C: Concern on
      product's property.
AB  - Point of care testing (POCT) is a new concept in laboratory medicine. The POCT
      tool helps perform the laboratory test at site giving fast result and requires
      only small amount of sample. It is presently and increasingly used in pediatrics.
      In pediatric diabetology, the use of POCT for following up of hemoglobin A1C is a
      new concept. At present, there are several POCT tools for this purpose. In this
      specific article, the author compares on important aspects (turnaround time and
      required amount of specimen) of 5 available POCT tools for measurement of
      hemoglobin A1C level. The test that is the fastest and requires the least amount
      of blood sample, which means the least harm to the pediatric patient is the most
      preferable. Here, it can be seen that there is no ideal POCT that has both
      properties. However, if it is standardized to compare the amount of required
      blood sample, the special concern in the pediatric patients, the product from
      multiplication shows that Siemen DCA 2000+ and Siemen DCA Vantage are the two
      most preferable POCT tools for hemoglobin A1C determination in pediatric diabetes
      mellitus management. 

PMID- 25572767
TI  - Usefulness of influenza vaccination in different groups of diabetic patients.
AB  - Diabetes mellitus is a common metabolic disorder that poses some degrees of
      immunodeficiency. This leads to the need for some specific primary prevention of
      infectious diseases by vaccination. An important vaccine for diabetic patients is
      the influenza vaccine. It is recommended that the diabetic patients should get
      vaccine. Here, the author performed an assessment on existed evidence to
      determine the usefulness of influenza vaccination in different groups of diabetic
      patients. 

PMID- 25572768
TI  - Diabetes, pancreatic cancer and vitamin D. Is there a link?
AB  - The role of vitamin D is not merely limited to maintaining skeletal health but
      also extends to maintaining glucose homeostasis by preserving insulin secretion
      and sensitivity and thus deficiency of vitamin D plays an important role in
      aetiopathogenesis of T2 diabetes. In addition to its many other roles, vitamin D
      has recently been found to have growth inhibiting affects on pancreatic cancer
      cells. Ecological studies have shown that there exists an inverse correlation
      between sun exposure and death rates for pancreatic cancer. Since vitamin D has
      promising role in both type 2 diabetes mellitus and pancreatic cancer, its
      deficiency may be associated to any or both of these chronic diseases. The
      present review thus aims to find correlation between diabetes and pancreatic
      cancer and if vitamin D is a common link between the two. 

PMID- 25572769
TI  - Sepsis in diabetes: A bad duo.
AB  - Increasing incidence of morbidity and mortality of diabetic subjects due to
      infection necessitates the understanding of its patho-biology and further
      remedial measures for its prevention and treatment. The increased incidence of
      infection is because of systemic illness that has compromising effects on
      multiple organs including the nervous, vascular, musculoskeletal, and immunologic
      systems of the diabetic patients. Many factors contribute to this condition
      including hyperglycemia, insulin deficiency, ischemia and impaired immunity.
      Sepsis, as a separate entity, lead to destruction of cytokine network that can be
      fatal. Compromised defense mechanisms due to sepsis and cytokine dysregulation in
      diabetic patients make the situation worse. Early identification of local
      infection by applying advanced molecular tools, appropriate selection of
      antibiotics, intensive wound management, control of glycemic status and
      supportive treatment can reduce the rate of morbidity and mortality due to sepsis
      in patients with diabetes. 

PMID- 25572770
TI  - A rare sequela after a case of early bariatric surgery tourism.

PMID- 25572771
TI  - Laparoscopic conversion of Roux-en-Y gastric bypass to sleeve gastrectomy for
      intractable marginal ulcer.

PMID- 25572772
TI  - Comment on: Accuracy of routine postoperative swallow study in predicting leak or
      obstruction after gastric bypass.

PMID- 25572775
TI  - Asymmetric catalysis activated by visible light.
AB  - Visible light driven organic chemistry has sparked much excitement over the last
      several years. This review summarizes recent progress in combining visible light
      activation with asymmetric catalysis, processes that are either mediated by
      photoinduced electron or energy transfer. The tasks of photoactivation and
      asymmetric catalysis are typically accomplished by dual catalyst systems but
      several recent reports demonstrate that they can also be effectively executed by
      single catalysts. Beyond the discovery of novel asymmetric transformations under
      mild reaction conditions, this contemporary area of organic chemistry holds
      promise for the development of economical and environmentally friendly methods
      for the asymmetric synthesis of chiral compounds. 

PMID- 25572773
TI  - Protein intake in infancy and carotid intima media thickness at 5 years--a
      secondary analysis from a randomized trial.
AB  - BACKGROUND: Nutrition in childhood has an influence on the cardiovascular
      function later on in life. European Childhood Obesity Project is a multicenter,
      randomized clinical intervention trial examining the effect of early protein
      intake on later health outcomes, particularly adiposity and related disorders.
      The aim of the study was to examine the effect of nutritional intervention-
      different protein intake in infancy on carotid intima-media thickness (cIMT) at 5
      years. The association of cardiovascular risk factors with cIMT was also
      assessed. METHODS: Healthy term formula-fed infants in five European countries
      were enrolled either to the higher (HP) or to the lower (LP) protein group.
      Observational group consisted of breastfed infants. Plasma insulin, glucose,
      lipid profile, IGF-1, apolipoprotein A1 and B were measured as well as
      anthropometric parameters of parents and a child, blood pressure and physical
      activity. RESULTS: No difference in cIMT between HP and LP group was observed.
      Insulin, HOMA-IR index and total IGF-1 were positively associated with cIMT but
      after adjustment for confounders only an inverse association between ApoA1 and
      positive between ApoB/ApoA1 and cIMT were significant. CONCLUSION: High versus
      low protein intake in infancy does not influence cIMT at 5 years. cIMT in healthy
      children at 5 years is associated with their apolipoprotein profile.

PMID- 25572776
TI  - Priorities for research on tropical viruses after the 2014 Ebola epidemic.

PMID- 25572774
TI  - Mechanism of Bronsted acid-catalyzed glucose dehydration.
AB  - We present the first DFT-based microkinetic model for the Bronsted acid-catalyzed
      conversion of glucose to 5-hydroxylmethylfurfural (HMF), levulinic acid (LA), and
      formic acid (FA) and perform kinetic and isotopic tracing NMR spectroscopy mainly
      at low conversions. We reveal that glucose dehydrates through a cyclic path. Our
      modeling results are in excellent agreement with kinetic data and indicate that
      the rate-limiting step is the first dehydration of protonated glucose and that
      the majority of glucose is consumed through the HMF intermediate. We introduce a
      combination of 1) automatic mechanism generation with isotopic tracing
      experiments and 2) elementary reaction flux analysis of important paths with NMR
      spectroscopy and kinetic experiments to assess mechanisms. We find that the
      excess formic acid, which appears at high temperatures and glucose conversions,
      originates from retro-aldol chemistry that involves the C6 carbon atom of
      glucose. 

PMID- 25572778
TI  - Exceptional responders: in search of the science behind the miracle cancer cures.

PMID- 25572779
TI  - What is the future for cancer clinical trials?

PMID- 25572777
TI  - Gene families as soft cliques with backbones: Amborella contrasted with other
      flowering plants.
AB  - BACKGROUND: Chaining is a major problem in constructing gene families. RESULTS:
      We define a new kind of cluster on graphs with strong and weak edges: soft
      cliques with backbones (SCWiB). This differs from other definitions in how it
      controls the "chaining effect", by ensuring clusters satisfy a tolerant edge
      density criterion that takes into account cluster size. We implement algorithms
      for decomposing a graph of similarities into SCWiBs. We compare examples of
      output from SCWiB and the Markov Cluster Algorithm (MCL), and also compare some
      curated Arabidopsis thaliana gene families with the results of automatic
      clustering. We apply our method to 44 published angiosperm genomes with
      annotation, and discover that Amborella trichopoda is distinct from all the
      others in having substantially and systematically smaller proportions of moderate
      and large-size gene families. CONCLUSIONS: We offer several possible
      evolutionary explanations for this result.

PMID- 25572780
TI  - Breakthrough targeted therapeutic approaches to squamous cell carcinoma of the
      head and neck.

PMID- 25572781
TI  - Pertuzumab-induced cardiotoxicity: safety compared with trastuzumab.

PMID- 25572782
TI  - Ipilimumab in the treatment of prostate cancer.
AB  - Ipilimumab (Yervoy((r)); Bristol-Myers Squibb, NY, USA) is a fully human
      monoclonal antibody targeting CTLA-4 and is approved for the treatment of
      metastatic melanoma. Preclinical and clinical studies have shown its activity in
      a number of different cancer types, including prostate cancer. Recently, the
      results from a Phase III study of ipilimumab in prostate cancer patients with
      prior docetaxel therapy were reported. Although the study did not meet the
      primary end point of improved overall survival, prespecified subset analyses
      suggested that ipilimumab may be more active in men with lower disease burden,
      which suggests that immunotherapy should be tested early in men with castration
      refractory prostate cancer. Immune-related adverse events are common and most can
      be well managed with standard immunosuppressive algorithms.

PMID- 25572783
TI  - Dovitinib (CHIR258, TKI258): structure, development and preclinical and clinical
      activity.
AB  - Dovitinib is an oral multikinase inhibitor targeting FGF receptors, PDGF
      receptors and VEGF receptors. Its activity against FGF receptors suggests its
      usefulness in treating cancers after the failure of VEGF/VEGF receptor-targeting
      agents. The identified dose and schedule to be used in further studies was 500 mg
      orally for 5 days on and 2 days off. Biological considerations and the results
      achieved in a Phase I/II trial suggested its activity in advanced renal cell
      carcinoma patients pretreated with a tyrosine kinase inhibitor and an mTOR
      inhibitor. Surprisingly, in a randomized controlled Phase III trial versus
      sorafenib in the same setting, dovitinib failed to demonstrate any superiority.
      At present, dovitinib is being tested in different tumor types. However,
      molecular-based patient selection seems to be key to fully exploit the activity
      of this drug.

PMID- 25572784
TI  - Risk of fatigue and hepatic and metabolic toxicities in patients with solid
      tumors treated with everolimus: a meta-analysis.
AB  - BACKGROUND: We performed a systematic review and meta-analysis of fatigue,
      hepatic and metabolic toxicities associated with everolimus intake in patients
      with solid tumors. METHODS: Eligible studies included randomized trials of
      patients with solid tumors on everolimus describing events of fatigue,
      hyperlipidemia, hyperglycemia and elevated alanine aminotransferase (ALT).
      RESULTS: After the exclusion of ineligible studies, a total of ten clinical
      trials were considered eligible for the meta-analysis. The relative risks of all
      grade fatigue, hyperglycemia, hyperlipidemia and elevated ALT were 1.31 (p <
      0.002), 3.06 (p < 0.0001), 2.54 (p = 0.0001) and 2.96 (p < 0.003), respectively.
      CONCLUSION: Our meta-analysis demonstrates that everolimus is associated with a
      significantly increased risk of all-grade fatigue, hyperglycemia, hyperlipidemia
      and elevated ALT.

PMID- 25572786
TI  - Prognostic and predictive factors in patients treated with chemotherapy for
      advanced urothelial cancer: where do we stand?
AB  - The standard of care for patients with local advanced or metastatic urothelial
      carcinoma is chemotherapy. However, results with this are rather disappointing,
      and validated prognostic factors and biomarkers of tumor response, which are
      useful in the decision-making process, are still lacking. PubMed databases were
      searched for articles published until November 2013. Several promising clinical
      and biological candidate prognostic factors or markers of tumor response to first
      or second-line therapy, such as hemoglobin, performance status, visceral
      metastasis and ERCC1, hENT1 and EMT markers, have been identified and described
      in this article. In summary, clinical parameters and molecular profiling could
      revolutionize the management of local advanced or metastatic urothelial cancer,
      but an improvement in individualized therapeutic approaches still seems distant.

PMID- 25572787
TI  - Pathology, therapy and prognosis of papillary renal carcinoma.
AB  - Papillary renal cell carcinoma (pRCC) accounts for approximately 10% of renal
      parenchymal tumors. There are two pRCC subtypes reported in several studies, but
      at present, there is limited molecular evidence to validate this pRCC subtyping
      in the daily routine. The utility of subtyping pRCC is based on reports
      describing that pRCC subtype is an independent predictor of outcome, with type 1
      tumors showing significantly better survival than type 2 tumors. In this article,
      we summarize the relevant knowledge on pRCC regarding tumor features: clinical
      presentation, histopathology, electron microscopy, immunohistochemistry,
      cytogenetics, genetic/molecular and prognosis. We present an overview of the
      currently available pRCC treatment options and some of the new promising agents.

PMID- 25572785
TI  - Metastatic castration-resistant prostate cancer: time for innovation.
AB  - Androgen deprivation is the mainstay of advanced prostate cancer treatment.
      Despite initial responses, almost all patients progress to castration-resistant
      prostate cancer (CRPC). The understanding of the biology of CRPC and the evidence
      that CRPC still remains driven by androgen receptor signaling led to the
      discovery of new therapeutic targets. In the last few years, large Phase III
      trials showed improvements in survival and outcomes and led to the approval of a
      CYP17 inhibitor (abiraterone), an androgen receptor antagonist (enzalutamide),
      the taxane cabazitaxel, an alpha-emitter (radium-223), the bone resorption
      targeting drug denosumab and an immunotherapy (sipuleucel-T). This article
      describes the molecular mechanisms underlying castration resistance, discusses
      recent and ongoing trials and offers some insights into identifying the best
      sequence of new drugs.

PMID- 25572788
TI  - Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma.
AB  - Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor
      on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this
      receptor frees T cells from the inhibitory effects of PD-L1 and allows them to
      mediate antitumor effects against cancer cells. In a large Phase I study of 411
      patients with melanoma, high durable response rates over a range of doses and
      schedules have been shown with very little toxicity. A Phase III study of
      pembrolizumab comparing two schedules of administration with the current standard
      treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations
      with other checkpoint inhibitors as well as other anticancer agents are also
      being evaluated. Approval of pembrolizumab for the treatment of melanoma is
      expected.

PMID- 25572789
TI  - The role of miRNAs in bone metastasis and their significance in the detection of
      bone metastasis: a review of the published data.
AB  - The preferential metastasis of cancer cells to bone disrupts the process of bone
      remodeling and results in serious complications. Although bone imaging techniques
      are well established for bone metastasis diagnosis, they still have limits.
      Recently, small noncoding RNA molecules, called miRNAs, have become the subject
      of interest in many molecular pathways in relation to bone metastasis.
      Furthermore, studies have demonstrated the ability to distinguish normal from
      cancerous cells and metastatic bone tumor origin based on miRNA profiles. Here,
      we summarize the data on mechanisms of osteolytic and osteoblastic bone
      metastases supporting the involvement of miRNA changes in the bone metastatic
      evolution. We also focus on the available evidence regarding current clinical
      studies of miRNA expression in the detection of bone metastases.

PMID- 25572790
TI  - What is the best strategy for targeting EGF receptors in non-small-cell lung
      cancer?
AB  - EGF receptors (EGFRs) are often overexpressed or constitutively activated in non
      small-cell lung cancer, and are an important therapeutic target. EGFR signaling
      can be blocked with tyrosine kinase inhibitors (TKIs) and anti-EGFR antibodies.
      Three EGFR-TKIs are approved as initial monotherapies in patients with EGFR
      activating mutations, and erlotinib has a role as maintenance and second-line
      therapy. Investigational anti-EGFR monoclonal antibodies plus standard first-line
      therapy improve survival in patients with advanced non-small-cell lung cancer,
      especially in tumors with high EGFR expression. Anti-EGFR antibodies inhibit EGFR
      signaling and have the potential to stimulate antibody-dependent cell-mediated
      cytotoxicity. Multikinase TKIs are investigational as first- and second-line
      therapies, as monotherapies and in combination with chemotherapy. This article
      summarizes the available clinical data for EGFR-targeted therapies.

PMID- 25572791
TI  - Understanding the non-pharmacological correlates of self-reported efficacy of
      antidepressants.
AB  - OBJECTIVE: To explore the non-pharmacological correlates of the perceived
      effectiveness of antidepressants (ADs), thereby enhancing understanding of the
      mechanisms involved in recovery from depression while taking ADs. METHOD: An
      online survey was completed by 1781 New Zealand adults who had taken ADs in the
      previous 5 years. RESULTS: All 18 psychosocial variables measured were associated
      with depression reduction, and 16 with improved quality of life (QoL). Logistic
      regression models revealed that the quality of the relationship with the
      prescriber was related to both depression reduction and improved QoL. In
      addition, depression reduction was related to younger age, higher income, being
      fully informed about ADs by the prescriber, fewer social causal beliefs for
      depression and not having lost a loved one in the 2 months prior to prescription.
      Furthermore, both outcome measures were positively related to belief in
      'chemical' rather than 'placebo' effects. CONCLUSION: There are multiple non
      pharmacological processes involved in recovery while taking ADs. Enhancing them,
      for example focusing on the prescriber-patient relationship and giving more
      information, may enhance recovery rates, with or without ADs.

PMID- 25572792
TI  - Assessment of the effectiveness of mouthwashes in reducing cariogenic biofilm in
      orthodontic patients: a systematic review.
AB  - OBJECTIVES: The use of fixed orthodontic appliances makes it difficult to clean
      the teeth and accessories associated with it. For this reason, orthodontic
      patients have used oral antiseptics as coadjuvent means to reduce cariogenic
      plaque. The aim of this systematic review was to evaluate the effectiveness of
      oral antiseptics on the reduction of cariogenic plaque on orthodontic patients.
      DATA: This review has been registered at PROSPERO--international prospective
      register of systematic reviews under the number CRD42013006857. SOURCES: A
      systematic review of the literature was conducted in the following electronic
      databases: Scopus, PubMed, Web of Science, Medline, Embase and Cochrane, Grey
      literature and Clinical Trials, without limitations on the year of publication or
      language. Clinical studies in patients with fixed orthodontic appliances, who
      were making use of oral mouthwashes in order to reduce cariogenic plaque, were
      included. Articles with patients using systemic drugs, syndromic patients, those
      using mouthwashes for other purposes and/or using different cleaning techniques,
      and clinical cases were excluded. After selection by title and abstract,
      potentially eligible articles were read in full. The methodological quality and
      risk of biases of articles included were evaluated according to the
      characteristics of the study, measurements and statistical analyses of the study.
      The methodological quality was classified as high, moderate or low. STUDY
      SELECTION: The search identified 2716 articles, of which 15 met the inclusion
      criteria. Of these, 8 analyzed chlorhexidine-based mouthwashes, while in 1
      article Cetylpyridinium was used; 1 analyzed the mouthwash containing
      sanguinaria; 1 the use of NaF; 2 articles the use of AmF/SnF2; 2 the use of
      Listerine((r)), 1 also analyzed the association between mouthwashes with
      octenidine and with PVP-I. Of the articles analyzed, 11 were classified as having
      high and 4 as having moderate methodological quality. CONCLUSION: There is
      evidence of effectiveness of the use of oral mouthwashes in the control of
      cariogenic plaque in patients with fixed orthodontic appliances. The
      orthodontists may suggest the use of oral antiseptics in the oral hygiene of
      their patients as coadjuvent means to reduce cariogenic plaque. CLINICAL
      SIGNIFICANCE: Given current evidence, orthodontists may prescribe mouthwash as an
      auxiliary method in the control of cariogenic biofilm in orthodontic patients.

PMID- 25572793
TI  - Maternal and Perinatal Factors of Importance for Occurrence and Severity of
      Infantile Haemangioma.
AB  - To determine which patient and maternal factors are associated with the
      occurrence and the severity of infantile haemangioma (IH), a single-centre
      retrospective observational study was conducted with 96 haemangioma patients and
      143 age-matched control babies, born in the same hospital between March 2012 and
      March 2013. The IH patients were selected according to diagnosis from
      dermatologists, either consulted from the department of paediatrics or in
      outpatient setting. Unplanned female children whose mothers smoked and/or
      consumed alcohol when pregnant was more likely to have IH (p < 0.0.05). The
      higher the birth weight, the more superficial the haemangioma (p = 0.023), and
      localised lesions were more common in singleton babies (p = 0.023) and babies
      conceived by normal fertilisation (p = 0.002). The occurrence and severity of IH
      is not only influenced by patient factors but also by maternal factors especially
      care during pregnancy period. By controlling these factors, the incidence and
      severity of IH may be lowered.

PMID- 25572794
TI  - Monodisperse Sr-La2O3 hybrid nanofibers for oxidative coupling of methane to
      synthesize C2 hydrocarbons.
AB  - The synergistic effects from combinations of each component's functionality in
      hybrid Sr-La2O3 nanofibers brought about an improved catalytic behaviour for
      oxidative coupling of methane carried out at high temperatures, which cannot be
      achieved over the conventional Sr doped La2O3 spherical catalyst. 

PMID- 25572795
TI  - Investigating genetic and environmental contributions to adolescent externalizing
      behavior in a collectivistic culture: a multi-informant twin study.
AB  - BACKGROUND: Little is known about the etiology of adolescents' externalizing
      behavior (Ext) in collectivistic cultures. We aimed to fill this gap by
      investigating the genetic and environmental influences on Ext in Chinese
      adolescents. The etiological heterogeneity of aggression (AGG) and rule breaking
      (RB) was also examined. METHOD: The study sample included 908 pairs of same-sex
      twins aged from 10 to 18 years (mean = 13.53 years, s.d. = 2.26). Adolescents'
      Ext were assessed with the Achenbach System of Empirically Based Assessment
      including Child Behavior Checklist, Teacher Report Form, and Youth Self-Report.
      RESULTS: Univariate genetic analyses showed that genetic influences on all
      measures were moderate ranging from 34% to 50%, non-shared environmental effects
      ranged from 23% to 52%, and shared environmental effects were significant in
      parent- and teacher-reported measures ranging from 29% to 43%. Bivariate genetic
      analyses indicated that AGG and RB shared large genetic influences (r g = 0.64
      0.79) but moderate non-shared environmental factors (r e = 0.34-0.52).
      CONCLUSIONS: Chinese adolescents' Ext was moderately influenced by genetic
      factors. AGG and RB had moderate independent genetic and non-shared environmental
      influences, and thus constitute etiologically distinct dimensions within Ext in
      Chinese adolescents. The heritability of AGG, in particular, was smaller in
      Chinese adolescents than suggested by previous data obtained on Western peers.
      This study suggests that the collectivistic cultural values and Confucianism
      philosophy may attenuate genetic potential in Ext, especially AGG.

PMID- 25572796
TI  - Impact of pathogen-directed antimicrobial therapy for ventilator-associated
      pneumonia in trauma patients on charges and recurrence.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) represents one of the driving
      forces behind antibiotic use in the ICU. In a previous study, we established a
      defined algorithm for treatment of hospital-acquired VAP dictated by the
      causative pathogen. The purpose of the current study was to evaluate the impact
      of this algorithm for hospital-acquired VAP on recurrence and charges in trauma
      patients. STUDY DESIGN: Patients with VAP secondary to MRSA, Acinetobacter
      baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, or
      Enterobacteriaceae during 5 years subsequent to the previous study were
      evaluated. All VAP were diagnosed using quantitative cultures of the
      bronchoalveolar lavage effluent. Duration of antimicrobial therapy was dictated
      by the causative pathogen. If microbiologic resolution, defined as <10(3) colony
      forming units/mL, was achieved, therapy was stopped by day 10. The remainder
      received 14 days of therapy. Recurrence was defined as >10(5) colony-forming
      units/mL on subsequent bronchoalveolar lavage performed within 2 weeks after
      completion of appropriate therapy. RESULTS: Five hundred and twenty-nine VAP
      episodes were identified in 381 patients. Overall recurrence was unchanged
      compared with the previous study (1.5% vs 2%; p = 0.3). There was a decrease in
      the number of bronchoalveolar lavages performed per patient compared with the
      previous study (1.6 vs 2.3; p = 0.24) and a reduction of 4.8 antibiotic days per
      VAP episode compared with the previous study. Both changes resulted in a
      cumulative reduction of $3,535.04 per patient, for a savings of $1.35 million
      during the study period. CONCLUSIONS: Hospital-acquired VAP can be managed
      effectively by a defined course of therapy dictated by the causative pathogen.
      Adherence to an established algorithm simplified the management of VAP and
      contributed to a cumulative reduction in patient charges without impacting
      recurrence.

PMID- 25572798
TI  - Longitudinal changes in the dopamine transporter and cognition in suicide
      attempters with charcoal burning.
AB  - Suicide with charcoal burning, which results in carbon monoxide (CO) poisoning,
      is common in Asia. This study was designed to elucidate associations between
      changes in the dopamine transporter (DAT) and cognitive function in patients
      following CO poisoning during a follow-up period of 6 months. Participants
      comprised 31 healthy controls (HCs) and 21 CO poisoning patients. Each subject
      underwent single photon emission computed tomography with [(99m)Tc] TRODAT-1 to
      measure DAT availability and completed a cognitive battery assessing attention,
      memory, and executive function. For CO poisoning patients, a second DAT
      measurement and repeated cognitive evaluations were performed 6 months later. At
      baseline, DAT availability over bilateral striatum in CO poisoning subjects was
      significantly lower than in HCs. After 6 months, there was no significant change
      of DAT availability in CO poisoning patients. CO poisoning patients also had
      worse cognitive performance in all domains compared with HCs at baseline. After 6
      months, most cognitive functions were significantly improved, except for the
      Wisconsin Card Sorting Test (WCST), a measure of executive function.
      Interestingly, changes in the WCST were significantly correlated with changes in
      DAT availability during the 6-month follow-up period. The persistence of reduced
      DAT availability and its association with impaired performance on the WCST
      indicate a crucial role of DAT in the recovery of executive function following CO
      poisoning. 

PMID- 25572799
TI  - Effects of donor/recipient human leukocyte antigen mismatch on human
      cytomegalovirus replication following liver transplantation.
AB  - BACKGROUND: Natural immunity against cytomegalovirus (CMV) can control virus
      replication after solid organ transplantation; however, it is not known which
      components of the adaptive immune system mediate this protection. We investigated
      whether this protection requires human leukocyte antigen (HLA) matching between
      donor and recipient by exploiting the fact that, unlike transplantation of other
      solid organs, liver transplantation does not require HLA matching, but some donor
      and recipient pairs may nevertheless be matched by chance. METHODS: To further
      investigate this immune control, we determined whether chance HLA matching
      between donor (D) and recipient (R) in liver transplants affected a range of
      viral replication parameters. RESULTS: In total, 274 liver transplant recipients
      were stratified according to matches at the HLA A, HLA B, and HLA DR loci. The
      incidence of CMV viremia, kinetics of replication, and peak viral load were
      similar between the HLA matched and mismatched patients in the D+/R+ and D-/R+
      transplant groups. D+/R- transplants with 1 or 2 mismatches at the HLA DR locus
      had a higher incidence of CMV viremia >3000 genomes/mL blood compared to patients
      matched at this locus (78% vs. 17%; P = 0.01). Evidence was seen that matching at
      the HLA A locus had a small effect on peak viral loads in D+/R- patients, with
      median peak loads of 3540 and 14,706 genomes/mL in the 0 and combined (1 and 2)
      mismatch groups, respectively (P = 0.03). CONCLUSION: Overall, our data indicate
      that, in the setting of liver transplantation, prevention of CMV infection and
      control of CMV replication by adaptive immunity is minimally influenced by HLA
      matching of the donor and recipient. Our data raise questions about immune
      control of CMV in the liver and also about the cells in which the virus is
      amplified to give rise to CMV viremia.

PMID- 25572800
TI  - Effectiveness of a computerized drug-monitoring program to detect and prevent
      adverse drug events and medication non-adherence in outpatient ambulatory care:
      study protocol of a randomized controlled trial.
AB  - BACKGROUND: Medications are an effective intervention for managing and preventing
      health problems but their benefit can be undermined by non-adherence or adverse
      drug events (ADEs). Since these issues may be interconnected, efforts to improve
      non-adherence should also include reduction of ADEs. We have developed the ISTOP
      ADE system (Information Systems-enabled Outreach for Preventing Adverse Drug
      Events), which enables timely monitoring and managing of ADEs. The objectives of
      this study are to determine whether the ISTOP-ADE system, compared to routine
      care, will reduce: a) the probability of discontinuing the use of prognosis
      altering medications; b) the probability of a patient experiencing a severe ADE;
      c) the proportion of patients experiencing ADEs, preventable ADEs and ameliorable
      ADEs; and d) health services utilization. METHODS/DESIGN: We will randomly assign
      2,200 adult ambulatory patients in the province of Quebec who have been
      prescribed an incident medication for the management or prevention of a chronic
      health condition, to routine care or the ISTOP-ADE system. The ISTOP-ADE system
      consists of an interactive voice response system (IVRS) paired with pharmacist
      support. The IVRS will call patients at 3 and 17 days post-prescription to
      determine if they are experiencing any problems and connect them with a
      pharmacist when required or desired by the patient. We will evaluate medication
      persistence at 180 days and health-care utilization using provincial
      administrative data. Two blinded physicians will ascertain ADE status through a
      case review. DISCUSSION: We expect the ISTOP-ADE intervention to be feasible and
      to improve the quality of patient care through improved medication adherence,
      reduced ADE duration and reduced number of ADEs resulting in an emergency
      department or inpatient encounter. This in turn could lower health-care
      utilization, saving costs and lowering the burden on emergency departments and
      family practices. The success of ISTOP-ADE would present opportunities to
      implement this intervention through health systems, health insurance agents and
      commercial pharmacies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT02059044. Date registered: 10 January 2014.

PMID- 25572801
TI  - Inhibition of S-phase kinase-associated protein 2-mediated p27 degradation
      suppresses tumorigenesis and the progression of hepatocellular carcinoma.
AB  - In order to determine the protein expression of S-phase kinase-associated protein
      2 (Skp2) and p27kip1, and to evaluate their possible prognostic values in
      malignant liver cancer, tissue samples from 50 patients and 40 controls were
      assessed and analyzed by immunohistochemistry and western blot analysis. Positive
      expression of Skp2 was observed in 35 (70.0%) of the hepatocellular carcinoma
      samples; however, the positive expression of p27kip1 was observed in 6 (15.0%) of
      the hepatocellular carcinoma samples. The expression of Skp2 was significantly
      negatively correlated with the expression of p27 (P<0.01). The results from
      Annexin V-propidium iodide staining and MTT assays indicated that interference of
      Skp2 significantly induced apoptosis and inhibited the proliferation of SSMC-7721
      cells. In addition, the levels of endogenous p27 increased in the HepG2 and SSMC
      7721 cells following transfection with siRNA specific to Skp2, suggesting that
      the Skp2-mediated degradation of p27kip1 was important in the proliferation of
      tumor cells. The present study, therefore, provided a molecular reference for the
      treatment of liver cancer.

PMID- 25572803
TI  - Strain-induced extrinsic high-temperature ferromagnetism in the Fe-doped
      hexagonal barium titanate.
AB  - Diluted magnetic semiconductors possessing intrinsic static magnetism at high
      temperatures represent a promising class of multifunctional materials with high
      application potential in spintronics and magneto-optics. In the hexagonal Fe
      doped diluted magnetic oxide, 6H-BaTiO3-delta, room-temperature ferromagnetism
      has been previously reported. Ferromagnetism is broadly accepted as an intrinsic
      property of this material, despite its unusual dependence on doping concentration
      and processing conditions. However, the here reported combination of bulk
      magnetization and complementary in-depth local-probe electron spin resonance and
      muon spin relaxation measurements, challenges this conjecture. While a
      ferromagnetic transition occurs around 700 K, it does so only in additionally
      annealed samples and is accompanied by an extremely small average value of the
      ordered magnetic moment. Furthermore, several additional magnetic instabilities
      are detected at lower temperatures. These coincide with electronic instabilities
      of the Fe-doped 3C-BaTiO3-delta pseudocubic polymorph. Moreover, the distribution
      of iron dopants with frozen magnetic moments is found to be non-uniform. Our
      results demonstrate that the intricate static magnetism of the hexagonal phase is
      not intrinsic, but rather stems from sparse strain-induced pseudocubic regions.
      We point out the vital role of internal strain in establishing defect
      ferromagnetism in systems with competing structural phases. 

PMID- 25572802
TI  - A co-culture genome-wide RNAi screen with mammary epithelial cells reveals
      transmembrane signals required for growth and differentiation.
AB  - INTRODUCTION: The extracellular signals regulating mammary epithelial cell growth
      are of relevance to understanding the pathophysiology of mammary epithelia, yet
      they remain poorly characterized. In this study, we applied an unbiased approach
      to understanding the functional role of signalling molecules in several models of
      normal physiological growth and translated these results to the biological
      understanding of breast cancer subtypes. METHODS: We developed and utilized a
      cytogenetically normal clonal line of hTERT immortalized human mammary epithelial
      cells in a fibroblast-enhanced co-culture assay to conduct a genome-wide small
      interfering RNA (siRNA) screen for evaluation of the functional effect of
      silencing each gene. Our selected endpoint was inhibition of growth. In rigorous
      postscreen validation processes, including quantitative RT-PCR, to ensure on
      target silencing, deconvolution of pooled siRNAs and independent confirmation of
      effects with lentiviral short-hairpin RNA constructs, we identified a subset of
      genes required for mammary epithelial cell growth. Using three-dimensional
      Matrigel growth and differentiation assays and primary human mammary epithelial
      cell colony assays, we confirmed that these growth effects were not limited to
      the 184-hTERT cell line. We utilized the METABRIC dataset of 1,998 breast cancer
      patients to evaluate both the differential expression of these genes across
      breast cancer subtypes and their prognostic significance. RESULTS: We identified
      47 genes that are critically important for fibroblast-enhanced mammary epithelial
      cell growth. This group was enriched for several axonal guidance molecules and G
      protein-coupled receptors, as well as for the endothelin receptor PROCR. The
      majority of genes (43 of 47) identified in two dimensions were also required for
      three-dimensional growth, with HSD17B2, SNN and PROCR showing greater than
      tenfold reductions in acinar formation. Several genes, including PROCR and the
      neuronal pathfinding molecules EFNA4 and NTN1, were also required for proper
      differentiation and polarization in three-dimensional cultures. The 47 genes
      identified showed a significant nonrandom enrichment for differential expression
      among 10 molecular subtypes of breast cancer sampled from 1,998 patients. CD79A,
      SERPINH1, KCNJ5 and TMEM14C exhibited breast cancer subtype-independent overall
      survival differences. CONCLUSION: Diverse transmembrane signals are required for
      mammary epithelial cell growth in two-dimensional and three-dimensional
      conditions. Strikingly, we define novel roles for axonal pathfinding receptors
      and ligands and the endothelin receptor in both growth and differentiation.

PMID- 25572804
TI  - Therapeutic efficacy evaluation of postoperative adjuvant radiotherapy in mid
      thoracic esophageal carcinoma patients underwent Ivor Lewis esophagectomy with
      two-field lymphadenectomy.
AB  - The objective of this paper is to study the treatment outcome of postoperative
      adjuvant radiation therapy in Ivor Lewis esophagectomy with two-field
      lymphadenectomy (2FL) and evaluate whether the method can replace three-field
      lymphadenectomy (3FL). We collected a consecutive series of 503 patients who had
      undergone Ivor Lewis esophagectomy with 2FL over a seven-year period in our
      department and evaluated the therapeutic efficacy of postoperative adjuvant
      radiation therapy. Recurrence and survival rates were calculated with the Kaplan
      Meier method, and the differences were compared by the log-rank test. Logistic
      regression analysis was used to test risk factors for postoperative lymph node
      metastasis. Cox regression analysis was used to identify prognostic risk factors.
      The overall 3- and 5-year survival rates were 62.8 and 34.4 %, respectively.
      There was a significant difference in 5-year survival rate between patients
      received adjuvant radiation therapy and did not receive radiation therapy.
      Postoperative adjuvant radiation therapy for patients who underwent Ivor Lewis
      esophagectomy with 2FL may offer the patients significant survival benefits and
      reduces the incidence of recurrence in cervical and superior mediastinal lymph
      nodes. 

PMID- 25572805
TI  - Increased drug resistance in breast cancer by tumor-associated macrophages
      through IL-10/STAT3/bcl-2 signaling pathway.
AB  - Tumor-associated macrophages (TAMs) appear to be the major component in solid
      tumor microenvironment, which were reported to play an important role in tumor
      malignant progression. Recently, TAMs were reported to be associated with drug
      resistance in some types of solid tumor including breast cancer. However, how
      TAMs regulate breast tumor resistance remains unknown. In this study, THP-1 cells
      were stimulated with PMA and IL-4/IL-13 to form M2-like macrophages to study the
      role of TAMs on chemoresistance. Our results showed that TAMs and its
      supernatants significantly prevent breast tumor cells from apoptosis caused by
      paclitaxel. We also found that the high level of IL-10 secreted by TAMS was
      responsible for drug resistance of breast cancer. The possible TAMs-modulated
      drug resistance mechanism involved may be associated with elevation of bcl-2 gene
      expression and up-regulation of STAT3 signaling in tumor cells. Furthermore, the
      blockage of TAMs-derived IL-10 by neutralizing antibody resulted in attenuation
      of STAT3 activation and decrease of bcl-2 mRNA expression, consequently enhanced
      sensitivity of breast cancer cells. Our data suggested that TAMs might induce
      drug resistance through IL-10/STAT3/bcl-2 signaling pathway, providing possible
      new targets for breast tumor therapy. 

PMID- 25572806
TI  - Human mammary microenvironment better regulates the biology of human breast
      cancer in humanized mouse model.
AB  - During the past decades, many efforts have been made in mimicking the clinical
      progress of human cancer in mouse models. Previously, we developed a human breast
      tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions
      between "species-specific" mammary microenvironment of human origin and human
      breast cancer cells. However, detailed evidences are absent. The present study
      (in vivo, cellular, and molecular experiments) was designed to explore the
      regulatory role of human mammary microenvironment in the progress of human breast
      cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were
      developed for in vivo comparisons. Then, the orthotopic tumor masses from three
      different mouse models were collected for primary culture. Finally, the biology
      of primary cultured human breast cancer cells was compared by cellular and
      molecular experiments. Results of in vivo mouse models indicated that human
      breast cancer cells grew better in human mammary microenvironment. Cellular and
      molecular experiments confirmed that primary cultured human breast cancer cells
      from HB mouse model showed a better proliferative and anti-apoptotic biology than
      those from SUB to MFP mouse models. Meanwhile, primary cultured human breast
      cancer cells from HB mouse model also obtained the migratory and invasive biology
      for "species-specific" tissue metastasis to human tissues. Comprehensive analyses
      suggest that "species-specific" mammary microenvironment of human origin better
      regulates the biology of human breast cancer cells in our humanized mouse model
      of breast cancer, which is more consistent with the clinical progress of human
      breast cancer. 

PMID- 25572808
TI  - Retraction note to: the hypoxia-inducible factor-1 regulates the microRNA185
      expression through binding to hypoxia response elements sequence 2.

PMID- 25572807
TI  - Trial of LVDP regimen (L-asparaginase, etoposide, dexamethasone, and cisplatin,
      followed by radiotherapy) as first-line treatment for newly diagnosed, stage
      III/IV extranodal natural killer/T cell lymphoma.
AB  - Stage III/IV extranodal natural killer/T cell lymphoma (ENKL) has a poor response
      and poor survival. Given the sensitivity of ENKL to radiotherapy and the fact
      that there is no consensus on standard chemotherapy, we conducted a clinical
      trial of LVDP regimen, combining LVDP chemotherapy (containing etoposide,
      dexamethasone, L-asparaginase, and cisplatin), followed by radiotherapy as a
      consolidation therapy regimen, for newly diagnosed patients with stage III/IV
      ENKL to evaluate the efficacy and safety of this regimen. The primary endpoints
      were overall response rate (ORR) and survival [overall survival (OS) and
      progression-free survival (PFS)] at 1 or 2 years, while the secondary endpoints
      were toxicity and adverse effects. In total, 18 patients were enrolled in this
      trial from July 2010 to September 2013. The mean completed cycles of chemotherapy
      was 4.04 (range 1-8 cycles), and the ORR was 50 %. During a mean follow-up of
      21.8 months (range 2-51 months), the 1-year OS and PFS rates were 72.2 and 50.0
      %, respectively, the 2-year OS and PFS rates were 33.3 and 22.2 %, respectively,
      and the median OS and PFS were 23.0 and 10.5 months, respectively. Severe adverse
      effects during therapy included six cases of grade 3/4 bone marrow suppression
      and one case of grade 3 transaminase increase. Sex, eastern cancer oncology
      group, performance status, Korean Prognostic Index, International Prognostic
      index, and bone marrow infiltration may influence the prognosis of advanced-stage
      ENKL. 

PMID- 25572809
TI  - Clinicopathological features of thirty patients with primary breast lymphoma and
      review of the literature.
AB  - Primary breast lymphoma (PBL) is a rare disease accounting for 0.4-0.5 % of all
      breast malignancies. Accumulating evidence indicates that the diagnosis,
      prognostic factors, and optimal management of PBL are difficult. The present
      study aims to investigate the clinicopathological features and optimal treatment
      of PBL and to evaluate the institutional experience in this patient population. A
      total of 30 patients with PBL from January 2002 to December 2012 treated in
      He'nan Province Tumor Hospital were selected. The patients' clinical and
      pathological characteristics, treatment and response data, patterns of
      recurrence, and outcomes were retrospectively analyzed, and the relevant
      literatures were reviewed. All the cases were female, and the median age was 45.
      Diffuse large B cell lymphoma was the most common histological subtype seen in 23
      of 30 patients. With a median follow-up time 32 months, median OS was 42 months
      (95 % CI 25-58 months), with 5-year OS rates 48 % (95 % CI 36-59 %). The median
      PFS was 14 months (95 % CI 6-30 months), with 5-year PFS rates 32 % (95 % CI 20
      45 %). The prognostic factors that retained statistical significance for OS were
      IPI (P < 0.001), age (P = 0.04), and stage (P < 0.001). For PFS, significant
      prognostic factors were IPI (P = 0.01), radiotherapy given (P = 0.02) and stage
      (P = 0.02). PBL appears to have a worse prognosis. The present treatment method
      for PBL is a comprehensive way of diagnostic surgery together with radiotherapy
      and chemotherapy. 

PMID- 25572810
TI  - MLF1 interacting protein: a potential gene therapy target for human prostate
      cancer?
AB  - Here, we investigated the role of one gene that has been previously associated
      with human prostate carcinoma cells-myelodysplasia/myeloid leukemia factor 1
      interacting protein (MLF1IP)-in order to better ascertain its role in human
      prostate carcinogenesis. The prostate cancer cell line PC-3 was lentivirally
      transfected to silence endogenous MLF1IP gene expression, which was confirmed by
      real-time quantitative PCR (RT-qPCR). Cellomics ArrayScan VTI imaging and MTT
      assays were conducted to assess cell proliferation. Cell cycle phase arrest and
      apoptosis were assayed by flow cytometry. Colony formation was assessed by
      fluorescence microscopy. MLF1IP gene expression was also analyzed by RT-qPCR in
      sixteen prostate cancer tissue samples and six healthy control prostate tissue
      samples from human patients. Cell proliferation was significantly inhibited in
      MLF1IP-silenced cells relative to control cells. G1 phase, S and G2/M phase cell
      counts were not significantly changed in MLF1IP-silenced cells relative to
      control cells. Apoptosis was significantly increased in MLF1IP-silenced cells,
      while MLF1IP-silenced cells displayed a significantly reduced number of cell
      colonies, compared to control cells. The 16 human prostate cancer tissue samples
      revealed no clear upregulation or downregulation in MLF1IP gene expression.
      MLF1IP significantly promotes prostate cancer cell proliferation and colony
      formation and significantly inhibits apoptosis without affecting cell cycle phase
      arrest. Further study is required to conclusively determine whether MLF1IP is
      upregulated in human prostate cancer tumors and to determine the precise cellular
      mechanism(s) for MLF1IP in prostate carcinogenesis. 

PMID- 25572811
TI  - Prognostic factors for survival with bevacizumab-based therapy in colorectal
      cancer patients: a systematic review and pooled analysis of 11,585 patients.
AB  - First-line chemotherapy + bevacizumab (BEV) is one of the standards of care in
      advanced colorectal cancer (CRC). Contrary to anti-EGFR agents, it is currently
      not possible to identify the ideal candidate for BEV-based chemotherapy due to
      the lack of predictors of outcomes. The aim of this study was to perform a
      systematic review of risk factors for survival after B-based chemotherapy for
      CRC. We performed a meta-analysis by searching on the databases PubMed, EMBASE,
      Web of Science and SCOPUS for a published series that focused on prognostic
      factors for BEV-based therapy in advanced CRC. Pooled hazard ratios (HR) were
      calculated by using a random-effects model for parameters that could be
      considered as potential prognostic factors in >=3 papers. Twenty-nine studies,
      which included a total of 11,585 patients, were considered in this analysis. Five
      parameters were associated with survival in >=3 papers: (1) a longer progression
      free interval [PFS: HR 0.87, 95 % confidence interval (CI) 0.78-0.97; P = 0.01];
      (2) a single site of metastases (HR 0.63, 95 % CI 0.56-0.71; P < 0.00001); (3)
      elevated lactate dehydrogenase (LDH: HR 2.08, 95 % CI 1.69-2.57; P < 0.00001);
      (4) KRAS mutation (HR 1.66, 95 % CI 1.36-2.03; P < 0.00001); and (5) poor
      performance status (PS: HR 1.99, 95 % CI 1.41-2.82; P < 0.0001). Clinical
      variables associated with prolonged survival, after first-line treatment with
      chemotherapy + BEV for metastatic CRC patients, included long PFS, low LDH
      levels, KRAS wild-type status, good PS and a single site of metastasis. They
      should be considered when stratifying patients for inclusion in randomized
      trials. Investigations into new prognostic factors based on tumor biology are
      needed and of high priority. 

PMID- 25572812
TI  - An Anticancer Drug Unit for the whole provincial oncologic network of Piacenza:
      improving safety and savings.
AB  - In recent years, the expenditure for cancer care is increased largely due to the
      increase in cancer prevalence, demographic changes and incorporation into
      clinical practice of new and expensive drugs. For these reasons, solutions to
      contain costs are necessaries. The drugs-related expenditure is proportionally
      higher in oncology than in other medical specialties and overcomes staffing costs
      for outpatient care. The introduction of additional measures to contain and
      reduce expenditures such as waste reduction and human resources optimization is
      highly desirable. On April 2013, we started a day-to-day monitoring of the
      consumption of drugs and developed an internal protocol for waste minimization,
      consisting of five measures. A computerized research through Medline, Cancerlit
      and Embase was performed, applying the words drug waste, cost-containment,
      Anticancer Drug Unit and stability instructions. Articles and abstracts were also
      identified by back-referencing from other relevant papers. Selected for the
      present review were papers published in English without limit of year. The day-to
      day monitoring of the consumption of drugs and the internal protocol for waste
      minimization were able to achieve a saving of <euro>15,700 every month. The
      projection of an annual cost-saving result of <euro>188.00 corresponds to a
      recovery of 4 % on the spending for oncologic drugs. Our data show that in a
      proper structure working according to the standards of quality, safety and
      sterility, preserving and reusing the drug waste within the limits imposed by the
      datasheets, it is possible to achieve a cost-containment policy and produce
      durable benefits. 

PMID- 25572813
TI  - Third-line chemotherapy with carboplatin, gemcitabine and liposomised doxorubicin
      for malignant pleural mesothelioma.
AB  - There is no well-defined standard third-line chemotherapy for advanced malignant
      pleural mesothelioma (MPM). However, combination of carboplatin, liposomised
      doxorubicin (Caelyx) and gemcitabine (CCG regimen) has revealed noteworthy
      activity when used as first-line treatment. The aim of this study is to assess
      efficacy and toxicity profile for patients with MPM receiving CCG regimen as a
      third-line treatment. Carboplatin (AUC 5), Caelyx (30 mg/m(2)) and Gemcitabine
      (1,000 mg/m(2)) day 1, together with Gemcitabine (800 mg/m(2)) day 8, were given
      in up to six cycles. Patients were unresectable, PS 0-2, and had previously
      received a first-line platinum-based regimen and either vinorelbine or pemetrexed
      as second line. Response to treatment was assessed by CT scan using Modified
      RECIST criteria for mesothelioma. Forty-three patients were treated between 2010
      and 2014. Median age was 67 years (47-82), 72 % males, and 79 % had previous
      asbestos exposure. Ninety per cent had PS 0-1, 58 % had epitheloid subtype and 63
      % IMIG stage IV. First-line treatment was platinum and pemetrexed in 42 cases.
      Second-line treatment was vinorelbine in 42 cases and pemetrexed in one patient.
      Median lead time from cessation of second-line treatment to start of third CCG
      was 1 month. Twenty-eight per cent of the patients received six cycles, while
      treatment was postponed due to toxicities, mainly haematological, in 56 % of
      cases. No toxicity-related deaths occurred. Partial response (PR) occurred in 14
      %, and disease control rate (DCR) was 60 %. Medians of overall survival (OS) from
      diagnosis and from start of CCG treatment were 25.2 months (18.4-31.5 months) and
      6.8 months (5.4-8.4 months), respectively. Progression-free survival (PFS) was
      4.1 months (1.7-4.5 months). Third-line CCG revealed a noteworthy efficacy with a
      DCR of 60.4 %. It was, however, associated with considerable haematological
      toxicity. Less toxic and more active treatment options are clearly needed. 

PMID- 25572814
TI  - Single-agent bevacizumab is an effective treatment in recurrent glioblastoma.
AB  - The aim of this study was to evaluate the efficiency and safety of single-agent
      bevacizumab therapy for recurrent glioblastoma multiforme (GBM). We identified
      patients with histologically confirmed glioblastoma and World Health Organization
      Grade III glioma who were previously treated with temozolomide plus radiotherapy
      and received 10 mg/kg bevacizumab intravenous infusion every 2 weeks until
      disease progression for recurrent disease. A total 24 patients included to this
      study. Twenty-two patients had GBM, and two patients had WHO grade III glioma. No
      complete response was observed, five patients (20.8 %) had partial response, nine
      patients (37.5 %) had stable diseases, and ten patients (41.7 %) had progressive
      diseases. The overall response rate was 20.8 %. The 6-month PFS rate (PFS6) and
      median PFS were determined as 37.5 % and 4.1 months, respectively. Median OS was
      6.4 months. Performance status of 17 (70.8 %) patients was improved following
      bevacizumab regimen. Univariate analysis showed that improvement in performance
      status (IPS) following bevacizumab therapy was a significant predictor of both
      PFS (p < 0.001) and OS (p < 0.020). Bevacizumab-related adverse effects were
      observed in 13 (54.1 %) patients. Grade 3-4 toxicity was observed in 4 (16.6 %)
      patients. Therapy interruptions were experienced in two patients due to adverse
      effects. Single-agent bevacizumab is an effective and safe treatment alternative
      in recurrent GBM. IPS following bevacizumab therapy was a significant predictor
      of both PFS and OS. 

PMID- 25572815
TI  - SOX5 promotes epithelial-mesenchymal transition and cell invasion via regulation
      of Twist1 in hepatocellular carcinoma.
AB  - The transcription factor sex determining region Y-box protein 5 (SOX5) plays
      important roles in various types of cancers. However, the expression and function
      of SOX5 in hepatocellular carcinoma (HCC) have not been elucidated. Here, we
      found that SOX5 is significantly up-regulated in HCC tissues and cell lines. Gain
      and loss-of-function studies demonstrated that SOX5 promoted HCC cell migration
      and invasion. In addition, we revealed that SOX5 is linked to epithelial
      mesenchymal transition (EMT) by regulation of Twist1. Our results indicate for
      the first time that SOX5 is a novel regulator of EMT in HCC and may be a
      potential therapeutic target for HCC metastasis. 

PMID- 25572816
TI  - Microwave ablation plus chemotherapy improved progression-free survival of
      advanced non-small cell lung cancer compared to chemotherapy alone.
AB  - The aim of the study was to determine survival benefit of the microwave ablation
      (MWA)/chemotherapy combination compared with chemotherapy alone. Patients with
      untreated, stage IIIB or IV NSCLC and at least one additional measurable site
      other than the ablative site were enrolled. They were divided into
      MWA/chemotherapy group and chemotherapy group. The primary endpoint was
      progression-free survival (PFS); secondary endpoints included response, time to
      local progression (TTLP), overall survival (OS), and adverse events (AEs). Forty
      six and twenty-eight patients were enrolled in the MWA/chemotherapy group and
      chemotherapy group, respectively. Complete ablation was observed in 84.8 %
      patients in the MWA/chemotherapy group. Median TTLP was 27.0 months. Objective
      response rate and disease control rate in MWA/chemotherapy group were 21.7 and
      76.1 %, and in the chemotherapy group were 32.1 % (p = 0.320) and 75.0 % (p =
      0.916), respectively. MWA/chemotherapy combination prolonged PFS
      [MWA/chemotherapy group 10.9 (95 % CI 5.1-16.7) ms vs. chemotherapy group 4.8 (95
      % CI 3.9-5.8) ms, p = 0.001] and tended to improve OS [MWA/chemotherapy group
      23.9 (95 % CI 15.2-32.6) ms vs. chemotherapy group 17.3 (95 % CI 15.2-19.3) ms, p
      = 0.140]. Multivariate analyses showed that MWA was an independent prognostic
      factor of PFS and primary tumor size was an independent prognostic factor of OS.
      AEs of MWA were observed in 67.4 % patients. Chemotherapy-associated AEs were
      observed in 39.1 and 53.6 % of patients in the MWA/chemotherapy and chemotherapy
      group, respectively. MWA/chemotherapy combination improved PFS of advanced NSCLC
      compared to chemotherapy alone, and the combination did not increase the adverse
      events of chemotherapy. 

PMID- 25572818
TI  - Patients with distal intestinal gastric cancer have superior outcome with
      addition of taxanes to combination chemotherapy, while proximal intestinal and
      diffuse gastric cancers do not: does biology and location predict chemotherapy
      benefit?
AB  - Gastric cancer, with one million new cases observed annually, and its dismal
      prognosis, is one of the leading causes of cancer-related mortalities. Systemic
      chemotherapy is the main treatment modality in advanced gastric cancer patients.
      We aim to evaluate the predictive role of tumor localization and histopathology
      on choosing three or two-drug combination regimens. Consecutive 110 metastatic
      gastric adenocarcinoma patients who were admitted to the Baskent University
      Department of Medical Oncology and the Van Research and Training Hospital were
      included in the study. Data of patients were analyzed retrospectively. Median age
      of patients was 58 years (range 30-80). Proximal intestinal, distal intestinal,
      and diffuse gastric cancers were found in 35 (32 %), 64 (58 %), and 11 (10 %)
      patients, respectively. 5-fluoracil and platinum (PF) and PFtax were administered
      to 47 (43 %) and 63 (57 %) patients, respectively. Median progression-free
      survival (PFS) was 4.0 (95 % CI 2.5-5.6) and 7.4 months (95 % CI 6.0-8.7) for PF
      and PFtax groups, (p = 0.034). When we used tumor localization as strata in the
      PFS survival curve, PFtax produced significantly higher PFS rates only in distal
      intestinal-type gastric cancer, compared with PF (p = 0.03). Median overall
      survival (OS) was 9.0 (95 % CI 5.2-12.3) and 17.3 months (95 % CI 7.8-27) for PF
      and PFtax groups, (p = 0.010). When we used tumor localization as strata in the
      OS survival curve, PFtax produced significantly higher OS rates only in distal
      intestinal-type gastric cancer compared with PF (p = 0.015). Pathology and tumor
      location in gastric cancers may affect the outcome, the addition of taxanes as a
      third drug may significantly increase PFS and OS rate purely in distal intestinal
      type gastric cancer but not in patients with proximal and diffuse-type gastric
      cancers. 

PMID- 25572819
TI  - Intraoperative neurophysiological monitoring in peripheral nerve surgery:
      Technical description and experience in a centre.
AB  - INTRODUCTION: Intraoperative neurophysiological monitoring has experienced a
      spectacular development in the past 20 years, particularly in the fields of
      neurosurgery and spine surgery. it has become a useful, almost indispensable,
      tool in preventing nerve damage during surgery. The aim of this article is to
      describe the intraoperative technique and analyze its results in the field of
      peripheral nerve surgery. OBJECTIVE: To describe the usefulness of a technique in
      peripheral nerve surgery, the technique used and the experience in a centre.
      PATIENTS AND METHODS: A retrospective study was conducted on 30 cases of
      peripheral nerve surgery performed in this centre from 2009 to 2013, using the
      intraoperative monitoring technique. RESULTS: Of the total of 13 peripheral nerve
      tumors recorded, there were 11 excellent results and 2 good results, one
      temporary hypoesthesia and one with almost complete sensory, except for motor,
      recovery. Traumatic injury was recorded in 17 cases, of which 6 required
      performing a graft, and the remaining 11 cases only neurolysis was performed,
      with complete motor and sensory recovery. CONCLUSIONS: Intraoperative
      neurophysiological monitoring is a useful tool in the secondary surgery of
      peripheral nerve injury and the intraneural tumor pathology.

PMID- 25572817
TI  - CCR7 pathway induces epithelial-mesenchymal transition through up-regulation of
      Snail signaling in gastric cancer.
AB  - The chemokine receptor 7 (CCR7) and Snail signaling have been linked to various
      types of cancers. The associations between these signalings and the epithelial
      mesenchymal transition (EMT) are not clear in gastric cancer. Here, the
      expression of CCR7 and Snail was detected in gastric cancer by
      immunohistochemistry and Western blot. Meanwhile, gastric cancer cells were
      subjected to CCL19, si-control, and si-Snail treatment. Cell cycle, migration,
      and invasion were also analyzed. The expression patterns of CCR7 and Snail were
      similar in either gastric cancer tissues or cells. The increased expression of
      CCR7 was closely associated with the increased Snail expression, which both were
      closely correlated with metastasis, stage and differentiation, and poor
      prognosis. The increased p-ERK, p-AKT, Snail, and MMP9 expression and the
      decreased E-cadherin were confirmed in MGC803 cells in a dose-dependent manner in
      response to CCL19 treatment. However, the blockade of Snail abrogated the up
      regulation of MMP9 and down-regulation of E-cadherin. CCR7-induced ERK and PI3K
      pathway regulated Snail signaling. Besides si-Snail treatment led to MGC803 cell
      cycle arrest and affected the migration and invasion. In conclusion, our study
      suggested that CCR7 promotes Snail expression to induce the EMT, resulting in
      cell cycle progression, migration, and invasion in gastric cancer. CCR7-Snail
      pathway provided more potential regimens for cancer therapy. 

PMID- 25572820
TI  - Long-term efficacy, safety and drug survival of ustekinumab in a Spanish cohort
      of patients with moderate to severe plaque psoriasis.
AB  - OBJECTIVE: To investigate the efficacy and safety of ustekinumab in clinical
      practice and the influence of several variables on response rates as well as on
      drug survival. METHODS: Retrospectively collected efficacy and safety data of a
      cohort of 67 consecutive patients treated with ustekinumab for moderate to severe
      psoriasis for at least 28 weeks and a maximum of 3 years. Drug survival was
      analyzed by the Kaplan-Meier method with log-rank test. RESULTS: PASI75 response
      rates were numerically higher in patients treated with 45 mg and patients naive
      to tumor necrosis factor (TNF)-blocking agents, at all time points. Drug survival
      was not significantly affected by any variable. CONCLUSION: Male sex, weight >100
      kg, obesity, and previous failure of one or more TNF inhibitors were associated
      with a diminished response to treatment. Obesity or previous exposure to anti-TNF
      agents was not associated with a diminished drug survival in this Spanish cohort.

PMID- 25572822
TI  - Autophagy facilitates the development of resistance to the tumor necrosis factor
      superfamily member TRAIL in breast cancer.
AB  - Autophagy, an important homeostatic cellular recycling mechanism, has emerged as
      a novel cytoprotective mechanism to increase tumor cell survival through escaping
      chemotherapy-induced cell death. To explore whether autophagy plays a protective
      role in the resistance to the tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL), we evaluated the autophagy levels in TRAIL-sensitive MDA-MB-231
      breast cancer cell lines and in TRAIL-refractory MDA-MB-231 cells before and
      after TRAIL treatment. After treatment with 40 ng/ml TRAIL, TRAIL-sensitized MDA
      MB-231 parental cells expressed higher level of LC3B protein and accumulated more
      autophagic vacuoles. Compared with TRAIL-sensitive MDA-MB-231, MDA-MB-231 TRAIL
      refractory cells showed higher levels of the lipidated form of LC3B and decreased
      p62/SQSTM1 protein expression, characterizing the occurrence of increased
      autophagic flux in TRAIL-refractory cells. Electron microscopy and
      monodansylcadaverine (MDC) autophagy-specific fluorescence staining analyses also
      revealed that the accumulation of autophagic vacuoles was drastically higher in
      TRAIL-refractory MDA-MB-231 parental cells. We demonstrated that chloroquine (CQ)
      and 2-(4-morpholinyl)-8-phenylchromone (LY294002) could effectively reduce TRAIL
      refractory breast cancer cell viability. Combination of TRAIL with CQ could
      effectively reverse the resistance of MDA-MB-231 TRAIL-refractory cells to TRAIL.
      Knockdown of light chain 3 (LC3) expression via small interfering RNA (siRNA)
      similarly resulted in reduced TRAIL-refractory cell proliferation and re
      sensitizing to TRAIL. This is the first report showing that breast cancer cells
      chronically exposed to TRAIL exhibit upregulation of the autophagic activity,
      indicating that autophagy efficiently protects breast cancer cells from TRAIL.
      Therapeutic targeting of autophagosome formation could be a novel molecular
      avenue to reduce the resistance of TRAIL in breast cancer.

PMID- 25572821
TI  - Estimation of prokaryotic supergenome size and composition from gene frequency
      distributions.
AB  - BACKGROUND: Because prokaryotic genomes experience a rapid flux of genes,
      selection may act at a higher level than an individual genome. We explore a
      quantitative model of the distributed genome whereby groups of genomes evolve by
      acquiring genes from a fixed reservoir which we denote as supergenome. Previous
      attempts to understand the nature of the supergenome treated genomes as random,
      independent collections of genes and assumed that the supergenome consists of a
      small number of homogeneous sub-reservoirs. Here we explore the consequences of
      relaxing both assumptions. RESULTS: We surveyed several methods for estimating
      the size and composition of the supergenome. The methods assumed that genomes
      were either random, independent samples of the supergenome or that they evolved
      from a common ancestor along a known tree via stochastic sampling from the
      reservoir. The reservoir was assumed to be either a collection of homogeneous sub
      reservoirs or alternatively composed of genes with Gamma distributed gain
      probabilities. Empirical gene frequencies were used to either compute the
      likelihood of the data directly or first to reconstruct the history of gene gains
      and then compute the likelihood of the reconstructed numbers of gains.
      CONCLUSIONS: Supergenome size estimates using the empirical gene frequencies
      directly are not robust with respect to the choice of the model. By contrast,
      using the gene frequencies and the phylogenetic tree to reconstruct multiple gene
      gains produces reliable estimates of the supergenome size and indicates that a
      homogeneous supergenome is more consistent with the data than a supergenome with
      Gamma distributed gain probabilities.

PMID- 25572824
TI  - Transparent Reporting of a Multivariable Prediction Model for Individual
      Prognosis or Diagnosis (TRIPOD): The TRIPOD Statement.
AB  - CONTEXT: Prediction models are developed to aid health care providers in
      estimating the probability or risk that a specific disease or condition is
      present (diagnostic models) or that a specific event will occur in the future
      (prognostic models), to inform their decision making. However, the overwhelming
      evidence shows that the quality of reporting of prediction model studies is poor.
      Only with full and clear reporting of information on all aspects of a prediction
      model can risk of bias and potential usefulness of prediction models be
      adequately assessed. OBJECTIVE: The Transparent Reporting of a multivariable
      prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative
      developed a set of recommendations for the reporting of studies developing,
      validating, or updating a prediction model, whether for diagnostic or prognostic
      purposes. EVIDENCE ACQUISITION: This article describes how the TRIPOD Statement
      was developed. An extensive list of items based on a review of the literature was
      created, which was reduced after a Web-based survey and revised during a 3-day
      meeting in June 2011 with methodologists, health care professionals, and journal
      editors. The list was refined during several meetings of the steering group and
      in e-mail discussions with the wider group of TRIPOD contributors. EVIDENCE
      SYNTHESIS: The resulting TRIPOD Statement is a checklist of 22 items, deemed
      essential for transparent reporting of a prediction model study. The TRIPOD
      Statement aims to improve the transparency of the reporting of a prediction model
      study regardless of the study methods used. The TRIPOD Statement is best used in
      conjunction with the TRIPOD explanation and elaboration document. CONCLUSIONS: To
      aid the editorial process and readers of prediction model studies, it is
      recommended that authors include a completed checklist in their submission (also
      available at www.tripod-statement.org). PATIENT SUMMARY: The Transparent
      Reporting of a multivariable prediction model for Individual Prognosis Or
      Diagnosis (TRIPOD) Initiative developed a set of recommendations for the
      reporting of studies developing, validating, or updating a prediction model,
      whether for diagnostic or prognostic purposes.

PMID- 25572825
TI  - Comparison of perioperative outcomes between robotic and laparoscopic partial
      nephrectomy: a systematic review and meta-analysis.
AB  - CONTEXT: Robotic partial nephrectomy (RPN) is rapidly increasing; however, the
      benefit of RPN over laparoscopic partial nephrectomy (LPN) is controversial.
      OBJECTIVE: To compare perioperative outcomes of RPN and LPN. EVIDENCE
      ACQUISITION: We searched Ovid-Medline, Ovid-Embase, the Cochrane Library,
      KoreaMed, KMbase, KISS, RISS, and KisTi from their inception through August 2013.
      Two independent reviewers extracted data using a standardized form. Quality of
      the selected studies was assessed using the methodological index for
      nonrandomized studies. EVIDENCE SYNTHESIS: A total of 23 studies and 2240
      patients were included. All studies were cohort studies with no randomization,
      and the methodological quality varied. There was no significant difference
      between the two groups regarding complications of Clavien-Dindo classification
      grades 1-2 (p=0.62), Clavien-Dindo classification grades 3-5 (p=0.78), change of
      serum creatinine (p=0.65), operative time (p=0.35), estimated blood loss
      (p=0.76), and positive margins (p=0.75). The RPN group had a significantly lower
      rate of conversion to open surgery (p=0.02) and conversion to radical surgery
      (p=0.0006), shorter warm ischemia time (WIT; p=0.005), smaller change of
      estimated glomerular filtration rate (eGFR; p=0.03), and shorter length of stay
      (LOS; p=0.004). CONCLUSIONS: This meta-analysis shows that RPN is associated with
      more favorable results than LPN in conversion rate to open or radical surgery,
      WIT, change of eGFR, and shorter LOS. To establish the safety and effectiveness
      outcomes of robotic surgery, well-designed randomized clinical studies with long
      term follow-up are needed. PATIENT SUMMARY: Robotic partial nephrectomy (PN) is
      more favorable than laparoscopic PN in terms of lower conversion rate to radical
      nephrectomy, a favorable renal function indexed estimated glomerular filtration
      rate, shorter length of hospital stay, and shorter warm ischemia time.

PMID- 25572823
TI  - GPCR-mediated EGF receptor transactivation regulates TRPV4 action in the
      vasculature.
AB  - BACKGROUND AND PURPOSE: Transient receptor potential vanilloid-4 (TRPV4) is a
      calcium-permeant ion channel that is known to affect vascular function. The
      ability of TRPV4 to cause a vasoconstriction in blood vessels has not yet been
      mechanistically examined. Further in neuronal cells, TRPV4 signalling can be
      potentiated by GPCR activation. Thus, we studied the mechanisms underlying the
      vascular contractile action of TRPV4 and the GPCR-mediated potentiation of such
      vasoconstriction, both of which are as yet unappreciated aspects of TRPV4
      function. EXPERIMENTAL APPROACH: The mechanisms of TRPV4-dependent regulation of
      vascular tone in isolated mouse aortae were studied using wire myography. TRPV4
      dependent calcium signalling and prostanoid production was studied in cultured
      human umbilical vein endothelial cells (HUVECs). KEY RESULTS: In addition to the
      well-documented vasorelaxation response triggered by TRPV4 activation, we report
      here a TRPV4-triggered vasoconstriction in the mouse aorta that involves a COX
      generated Tx receptor (TP) agonist that acts in a MAPK and Src kinase signalling
      dependent manner. This constriction is potentiated by activation of the GPCRs for
      angiotensin (AT1 receptors) or proteinases (PAR1 and PAR2) via transactivation of
      the EGF receptor and a process involving PKC. TRPV4-dependent vascular
      contraction can be blocked by COX inhibitors or with TP antagonists. Further,
      TRPV4 activation in HUVECs stimulated Tx release as detected by an elisa.
      CONCLUSION AND IMPLICATIONS: We conclude that the GPCR potentiation of TRPV4
      action and TRPV4-dependent Tx receptor activation are important regulators of
      vascular function and could be therapeutically targeted in vascular diseases.

PMID- 25572826
TI  - A Population-based Survey of the Prevalence, Potential Risk Factors, and Symptom
      specific Bother of Lower Urinary Tract Symptoms in Adult Chinese Women.
AB  - BACKGROUND: Epidemiological studies of lower urinary tract symptoms (LUTS) are
      few in China, and none has been conducted nationwide. OBJECTIVE: To estimate the
      prevalence and potential risk factors of LUTS and the bother they impose on adult
      women in China. DESIGN, SETTING, AND PARTICIPANTS: This is the second analysis of
      a population-based cross-sectional survey on urinary incontinence conducted
      between February and July 2006 in six regions of China. Cluster samples were
      randomly selected for interviews. INTERVENTIONS: No intervention was implemented.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A modified Chinese Bristol Female
      Lower Urinary Tract Symptoms questionnaire was administered. The participants
      were asked about the presence of individual LUTS and rated their symptom bother.
      Descriptive statistics, chi(2) tests, receiver operating characteristic curves,
      and multivariate logistic regressions were used for data analysis. RESULTS AND
      LIMITATIONS: A total of 18 992 respondents (94.96%) were included. The prevalence
      of any LUTS, storage symptoms, or voiding symptoms was 55.5%, 53.9%, and 12.9%,
      respectively, and increased with age. Nocturia was the most common symptom
      (23.4%), followed by urgency (23.3%) and stress urinary incontinence (SUI;
      18.9%). Nocturia was most frequently rated as bothersome (93.0%) but was
      generally minor (80.5%). Urgency and urgency urinary incontinence (UUI) were most
      frequently reported as severe (11.5% and 10.8%) or moderate (18.5% and 16.8%)
      bothers. Any LUTS were more prevalent in urban women (57.1% vs 53.9%). Multiple
      factors increased the odds of bother and individual LUTS, and older age and
      coexisting pelvic organ prolapse were strong predictors (p<0.05). This survey was
      conducted 8 yr ago and did not assess all LUTS. CONCLUSIONS: Half of adult women
      suffered with LUTS; nocturia, urgency, and SUI were more prevalent. Urgency and
      UUI were most frequently reported as severe or moderate bothers. Multiple factors
      influenced bother and individual LUTS. PATIENT SUMMARY: The prevalence of lower
      urinary tract symptoms is high and increases with age in adult women in China.
      Urgency and urgency urinary incontinence were most frequently regarded as severe
      or moderate bothers and should be targeted for medical intervention.

PMID- 25572827
TI  - Diversity-oriented synthesis of acyclic nucleosides via ring-opening of vinyl
      cyclopropanes with purines.
AB  - The diversity-oriented synthesis of acyclic nucleosides has been achieved via
      ring-opening of vinyl cyclopropanes with purines. With Pd2(dba)3.CHCl3 as a
      catalyst, the 1,5-ring-opening reaction proceeded well and afforded N9 adducts as
      the major form, in which the C=C bonds in the side chain were exclusively E-form.
      In the presence of AlCl3, the 1,3-ring-opening reaction occurred smoothly, giving
      N9 adducts as the dominate products. Meanwhile, when MgI2 was used as the
      catalyst, the 1,3-ring-opening reaction also worked well to form N7 adducts.

PMID- 25572828
TI  - The relationship between ART adherence and smoking status among HIV+ individuals.
AB  - Smoking is highly prevalent among HIV+ individuals and studies indicate that it
      may be associated with poor ART adherence, though the relationship is poorly
      understood. In addition little is known about interest in quitting among HIV+
      smokers who are having adherence difficulties. We examined smoking and ART
      adherence among 203 HIV+ individuals enrolled in a randomized trial of
      interventions to increase ART adherence. Prior analyses indicated there were no
      overall treatment group effects. Smoking status and motivation to quit was
      assessed at baseline and ART adherence was assessed at week 12, 24, 36, and 48.
      Longitudinal generalized estimating equation analysis that controlled for
      treatment group revealed that smoking status was not significantly related to
      adherence over time. Motivation to quit was high with 58 % intending to quit in
      the next 6 months and 25 % intending to quit in the next 30 days. Findings
      suggest that smoking is not associated with adherence among those with adherence
      difficulties. However it does not diminish importance of addressing both
      behaviors especially given HIV+ smokers substantial interest in changing smoking
      behavior. 

PMID- 25572829
TI  - Antiretroviral Therapy Adherence and Use of an Electronic Shared Medical Record
      Among People Living with HIV.
AB  - Electronic shared medical records (SMR) are emerging healthcare technologies that
      allow patients to engage in their healthcare by communicating with providers,
      refilling prescriptions, scheduling appointments, and viewing portions of medical
      records. We conducted a pre-post cohort study of HIV-positive adults who used and
      did not use SMR in two integrated healthcare systems. We compared the difference
      in antiretroviral refill adherence between SMR users and age- and sex-frequency
      matched non-users from the 12-month period prior to SMR useto the 12-month period
      starting 6 months after initiation of SMR use. High adherence was maintained
      among SMR users (change = -0.11 %) but declined among non-users (change = -2.05
      %; p = 0.003). Among SMR users, there was a steady improvement in adherence as
      monthly frequency of SMR use increased (p = 0.009). SMR use, particularly more
      frequent use, is associated with maintaining high adherence and non-use is
      associated with declines in adherence over time among patients with access to
      these online services.

PMID- 25572831
TI  - The Relationship Between Online Social Network Use, Sexual Risk Behaviors, and
      HIV Sero-Status Among a Sample of Predominately African American and Latino Men
      Who have Sex with Men (MSM) Social Media Users.
AB  - Social networking technologies have emerged as potential platforms to reach
      HIV(+) MSM in HIV interventions. This study sought to compare use of online
      social networking sites (SNSs) and sexual risk behaviors between HIV(+) and HIV(
      ) individuals among a sample of predominately African American and Latino SNS
      using MSM. A total of 112 MSM Facebook users were recruited online and offline
      and completed an online survey. We performed regression models to assess the
      association between HIV status, SNS use, and sexual risk behaviors. After
      adjusting for age, race, and employment status, being HIV positive was
      significantly associated with a greater number of sexual partners (ARR = 2.84, p
      = 0.0017) and lower comfort levels of discussing HIV/STI status on SNSs (AOR:
      0.23, p = 0.011). Findings suggest that HIV status is associated with sexual risk
      behaviors and SNS use among SNS-using MSM. We discuss the implications for online
      HIV prevention.

PMID- 25572830
TI  - mHealth Technology as a Persuasive Tool for Treatment, Care and Management of
      Persons Living with HIV.
AB  - Mobile health (mHealth) technology can be a valuable tool in the management of
      chronic illnesses, including HIV. Qualitative research methods were used to
      identify the desired content and features of a mobile app for meeting and
      improving the healthcare needs of persons living with HIV (PLWH). We conducted
      six focus group sessions with 50 English-or Spanish-speaking PLWH in New York
      City. To inform data analysis and to illustrate how mHealth technology can be
      used as a persuasive strategy for improving the health of PLWH, we integrated
      Fogg's functional role triad for computing technology model with the self
      determination theory to illustrate how mHealth technology can be used as a
      persuasive strategy for improving the health of PLWH. Participants suggested
      several tools for meeting their healthcare needs, including: reminders/alerts,
      lab results tracking, and notes on health status. mHealth technology can function
      as a social actor by providing chat boxes/forums, testimonials of lived
      experiences, and personal outreach. Examples of media that can be used as a
      persuasive technology include games/virtual rewards, coding of health tasks, and
      simulations on how to connect with PLWH. Findings from these focus groups can be
      used to design a mobile app for PLWH that is targeted to meet their healthcare
      needs. 

PMID- 25572832
TI  - Network Influences on the Sexual Risk Behaviors of Gay, Bisexual and Other Men
      Who Have Sex with Men Using Geosocial Networking Applications.
AB  - Geosocial networking applications (GSN apps) have become increasingly popular
      among gay, bisexual and other men who have sex with men (MSM). Our study sought
      to understand whether inclusion of individuals met via GSN apps in participants'
      social networks was associated with increased HIV risk behaviors among a
      probability sample of GSN app using MSM (N = 295) recruited in Los Angeles,
      California. Approximately 20 % of participants included a GSN app-met individual
      as one of their top five closest social network members. Those with a GSN app-met
      network member had more recent (past 30-day) sexual partners (B = 1.21, p <
      0.05), were nearly twice as likely to have engaged in unprotected anal
      intercourse (UAI) with their last sexual partner (AOR = 2.02, p < 0.05), and were
      nearly four times as likely to have engaged in UAI with their last GSN app-met
      sexual partner (AOR = 3.98, p < 0.001). Network-based interventions delivered via
      GSN apps may be useful in preventing the spread of HIV among MSM.

PMID- 25572833
TI  - Socioeconomic gradients in internalized stigma among 4,314 persons with HIV in
      sub-Saharan Africa.
AB  - The stigma attached to HIV is a major public health problem given its adverse
      impacts on HIV prevention and on the psychosocial wellbeing of persons with HIV.
      In this study, I apply a novel method to data from the Demographic and Health
      Surveys to identify persons with HIV who were aware of their seropositivity at
      the time of the survey. The pooled dataset includes 4,314 persons with HIV in
      Cameroon, Ethiopia, Gabon, Kenya, Lesotho, Malawi, Rwanda, Swaziland, Tanzania,
      Uganda, Zambia, and Zimbabwe. My findings indicate that nearly one-fifth of study
      participants provided survey responses consistent with internalization of
      stigmatizing beliefs. Furthermore, in multivariable regression models, striking
      socioeconomic gradients in internalized stigma were observed. A clear implication
      of my findings is that the adverse health and psychosocial impacts of HIV stigma
      are likely concentrated among those with the fewest socioeconomic resources for
      managing and resisting it. 

PMID- 25572834
TI  - Gay Apps for Seeking Sex Partners in China: Implications for MSM Sexual Health.
AB  - Anti-gay stigma and harsh local environments in many low and middle-income
      countries (LMIC) encourage men who have sex with men (MSM) partner-seeking mobile
      application (gay app) use. To investigate the sexual risk profiles of gay app
      users and guide future HIV prevention programs, we conducted a cross-sectional
      online survey among 1,342 MSM in China examining associations between gay app use
      and sexual behaviors, including HIV and sexually transmitted disease testing.
      Compared to non-app users, app users were more likely to be younger, better
      educated, "out" about their sexual orientation, and single. They were also more
      likely to report multiple recent sex partners and HIV testing, but there was no
      difference in condomless sex between the two groups. Future research among MSM in
      LMIC is needed to characterize gay app use and explore its potential for future
      public health interventions. 

PMID- 25572835
TI  - Characterization of human bladder cell membrane during cancer transformation.
AB  - Phenomena associated with changes in cell membranes are thought to play an
      important role in the cancer transformation. We hypothesized that the electrical
      charge of tumor cells can indirectly represent membrane-based changes that have
      occurred during cell transformation and may indicate tumor cell status. Here, we
      describe work showing that phospholipids, proteins content, and electric charge,
      are all altered in the cell membranes of pT2 stage/grade G3 bladder cancer.
      Qualitative and quantitative phospholipid composition and the presence of
      integral membrane proteins were identified using high-performance liquid
      chromatography. Protein composition was determined using selective hydrolysis of
      isolated bladder cell membrane proteins and peptide resolution. The surface
      charge density of human bladder cell membranes was determined using
      electrophoresis. Our results show that cancer transformation is associated with
      increased phospholipid levels and a decreased level of integral proteins.
      Moreover, the process of cancer transformation significantly enhanced changes in
      the surface charge density of the human bladder cell membrane. In conclusion,
      this study demonstrates that cell membrane structure and function are modified in
      bladder cancer cells and that further work in this area is warranted. 

PMID- 25572836
TI  - Amazonian freshwater habitats experiencing environmental and socioeconomic
      threats affecting subsistence fisheries.
AB  - Matching the trend seen among the major large rivers of the globe, the Amazon
      River and its tributaries are facing aquatic ecosystem disruption that is
      affecting freshwater habitats and their associated biodiversity, including trends
      for decline in fishery resources. The Amazon's aquatic ecosystems, linked natural
      resources, and human communities that depend on them are increasingly at risk
      from a number of identified threats, including expansion of agriculture; cattle
      pastures; infrastructure such as hydroelectric dams, logging, mining; and
      overfishing. The forest, which regulates the hydrological pulse, guaranteeing the
      distribution of rainfall and stabilizing seasonal flooding, has been affected by
      deforestation. Flooding dynamics of the Amazon Rivers are a major factor in
      regulating the intensity and timing of aquatic organisms. This study's objective
      was to identify threats to the integrity of freshwater ecosystems, and to seek
      instruments for conservation and sustainable use, taking principally fish
      diversity and fisheries as factors for analysis. 

PMID- 25572837
TI  - Small RNA sequencing identifies miRNA roles in ovule and fibre development.
AB  - MicroRNAs (miRNAs) have been found to be differentially expressed during cotton
      fibre development. However, which specific miRNAs and how they are involved in
      fibre development is unclear. Here, using deep sequencing, 65 conserved miRNA
      families were identified and 32 families were differentially expressed between
      leaf and ovule. At least 40 miRNAs were either leaf or ovule specific, whereas 62
      miRNAs were shared in both leaf and ovule. qRT-PCR confirmed these miRNAs were
      differentially expressed during fibre early development. A total of 820 genes
      were potentially targeted by the identified miRNAs, whose functions are involved
      in a series of biological processes including fibre development, metabolism and
      signal transduction. Many predicted miRNA-target pairs were subsequently
      validated by degradome sequencing analysis. GO and KEGG analyses showed that the
      identified miRNAs and their targets were classified to 1027 GO terms including
      568 biological processes, 324 molecular functions and 135 cellular components and
      were enriched to 78 KEGG pathways. At least seven unique miRNAs participate in
      trichome regulatory interaction network. Eleven trans-acting siRNA (tasiRNA)
      candidate genes were also identified in cotton. One has never been found in other
      plant species and two of them were derived from MYB and ARF, both of which play
      important roles in cotton fibre development. Sixteen genes were predicted to be
      tasiRNA targets, including sucrose synthase and MYB2. Together, this study
      discovered new miRNAs in cotton and offered evidences that miRNAs play important
      roles in cotton ovule/fibre development. The identification of tasiRNA genes and
      their targets broadens our understanding of the complicated regulatory mechanism
      of miRNAs in cotton. 

PMID- 25572839
TI  - Neutral N^C^N terdentate luminescent Pt(II) complexes: their synthesis,
      photophysical properties, and bio-imaging applications.
AB  - An emerging field regarding N^C^N terdentate Pt(II) complexes is their
      application as luminescent labels for bio-imaging. In fact, phosphorescent Pt
      complexes possess many advantages such as a wide emission color tunability, a
      better stability towards photo- and chemical degradation, a very large Stokes
      shift, and long-lived luminescent excited states with lifetimes typically two to
      three orders of magnitude longer than those of classic organic fluorophores.
      Here, we describe the synthesis and photophysical characterization of three new
      neutral N^C^N terdentate cyclometallated Pt complexes as long-lived bio-imaging
      probes. The novel molecular probes bear hydrophilic (oligo-)ethyleneglycol chains
      of various lengths to increase their water solubility and bio-compatibility and
      to impart amphiphilic nature to the molecules. The complexes are characterized by
      a high cell permeability and a low cytotoxicity, with an internalization kinetics
      that depends on both the length of the ethyleneglycol chain and the ancillary
      ligand.

PMID- 25572838
TI  - A retrospective study of septic arthritis in a tertiary hospital in West Texas
      with high rates of methicillin-resistant Staphylococcus aureus infection.
AB  - Septic arthritis is an important concern for rheumatologists in the evaluation of
      joint disease. Very few studies have addressed the microbiologic epidemiology and
      outcomes of septic arthritis in the USA since the year 2000. We performed a
      retrospective study of septic arthritis in a tertiary hospital in West Texas from
      the year 2000 to 2013. We recorded data on patient demographics, microbiologic
      etiology, treatment patterns, and outcomes. The most common causative organisms
      were Staphylococcus aureus and Streptococcus spp. Methicillin-resistant
      Staphylococcus aureus (MRSA) caused septic arthritis in 22.6 % of the cases. MRSA
      septic arthritis was associated with low rates of adequate empiric antimicrobial
      therapy. The mortality due to sepsis in our study was 5.5 %. Patients with septic
      arthritis had a mean length of stay of 13.5 +/- 12.1 days and required 2.1 +/-
      1.4 joint operations. Many patients (29.2 %) had readmissions due to
      complications, and these patients had high rates of home health utilization and
      transfers to other facilities post hospital discharge. In our logistic regression
      analysis model, factors associated with poor outcomes in septic arthritis were
      MRSA, older age, and prosthetic joint infection. Septic arthritis is associated
      with significant mortality, morbidity, and health care costs, and more studies
      are needed to improve outcomes, especially considering the increasing rates of
      MRSA as the pathogen. 

PMID- 25572840
TI  - Phytochemicals and their potential usefulness in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the
      gastrointestinal tract with unclear etiology, namely ulcerative colitis and
      Crohn's disease. Various drug therapies including aminosalicylates and
      immunomodulators have been approved for use; they have shown to produce diverse
      side effects. To overcome these limitations of the current therapeutics for IBD,
      extensive research is underway to identify drugs that are effective and free of
      undesirable side effects. Recently, various naturally occurring phytochemicals
      that cover a wide range of chemical entities such as polyphenols, terpeniods,
      flavonoids, and alkaloids have received attention as alternative candidates for
      IBD therapy. These phytochemicals act by modulating the immune response, various
      transcription factors, or reduce cytokine secretion. This review summarizes the
      findings of recent studies on phytochemicals as therapeutic agents in the
      management of IBD.

PMID- 25572841
TI  - The virtual university: digital tools for e-learning and remote learning are
      becoming an increasingly important tool for teaching at universities.

PMID- 25572842
TI  - Penetrability of the inner mucus layer: who is out there?

PMID- 25572843
TI  - Positive feedback regulation of type I interferon by the interferon-stimulated
      gene STING.
AB  - Stimulator of interferon genes (STING) is an important regulator of the innate
      immune response to cytoplasmic DNA. However, regulation of STING itself is
      largely unknown. Here, we show that STING transcription is induced by innate
      immune activators, such as cyclic dinucleotides (CDNs), through an IFNAR1- and
      STAT1-dependent pathway. We also identify a STAT1 binding site in the STING
      promoter that contributes to the activation of STING transcription. Furthermore,
      we show that induction of STING mediates the positive feedback regulation of CDN
      triggered IFN-I. Thus, our study demonstrates that STING is an interferon
      stimulated gene (ISG) and its induction is crucial for the IFN-I positive
      feedback loop. 

PMID- 25572852
TI  - Decreased expression of sestrin 2 predicts unfavorable outcome in colorectal
      cancer.
AB  - Sestrin 2 is a conserved antioxidant protein that is involved in p53-dependent
      antioxidant defenses and protects cells against oxidative stresses. The present
      study was conducted to examine the expression of sestrin 2 in colorectal cancer
      (CRC) and investigate a possible relationship between sestrin 2 expression and
      prognosis in CRC. The expression of sestrin 2 in human CRC tissues and cell lines
      was evaluated by immunohistochemical or immunofluorescent staining and western
      blot analysis. The correlations between sestrin 2 expression in human CRC tissues
      and clinicopathological variables, including overall survival (OS) and disease
      free survival (DFS), were analyzed. Both human CRC tissues and cell lines showed
      a decreased expression of sestrin 2. Furthermore, a low expression of sestrin 2
      was significantly correlated with advanced tumor stage, lymphatic invasion, lymph
      node metastasis, vascular invasion and liver metastasis. Survival analysis showed
      that patients with low sestrin 2 staining had a significantly worse DFS and OS.
      Additionally, early or advanced stage CRC patients with a low expression of
      sestrin 2 had a shorter survival. In univariate analysis, the patients with low
      sestrin 2 expression, advanced tumor stage, lymphatic invasion, lymphatic node
      metastasis, vascular invasion, liver metastasis and peritoneal metastasis had
      shorter OS and DFS. In multivariate analysis, only low sestrin 2 expression,
      advanced tumor stage, lymphatic node metastasis, vascular invasion and liver
      metastasis remained as independent prognostic factors of poor OS and DFS. The
      findings suggested that a decreased expression of sestrin 2 is associated with an
      unfavorable prognosis, which suggests that it is a novel and crucial predictor
      for CRC metastasis.

PMID- 25572844
TI  - Cabut/dTIEG associates with the transcription factor Yorkie for growth control.
AB  - The Drosophila transcription factor Cabut/dTIEG (Cbt) is a growth regulator,
      whose expression is modulated by different stimuli. Here, we determine Cbt
      association with chromatin and identify Yorkie (Yki), the transcriptional co
      activator of the Hippo (Hpo) pathway as its partner. Cbt and Yki co-localize on
      common gene promoters, and the expression of target genes varies according to
      changes in Cbt levels. Down-regulation of Cbt suppresses the overgrowth
      phenotypes caused by mutations in expanded (ex) and yki overexpression, whereas
      its up-regulation promotes cell proliferation. Our results imply that Cbt is a
      novel partner of Yki that is required as a transcriptional co-activator in growth
      control. 

PMID- 25572854
TI  - [Possibilities for non-invasive diagnostics of focal hepatic lesions by
      innovative imaging procedures].

PMID- 25572853
TI  - Phosphorylation of caveolin-1 on tyrosine-14 induced by ROS enhances palmitate
      induced death of beta-pancreatic cells.
AB  - A considerable body of evidence exists implicating high levels of free saturated
      fatty acids in beta pancreatic cell death, although the molecular mechanisms and
      the signaling pathways involved have not been clearly defined. The membrane
      protein caveolin-1 has long been implicated in cell death, either by sensitizing
      to or directly inducing apoptosis and it is normally expressed in beta cells.
      Here, we tested whether the presence of caveolin-1 modulates free fatty acid
      induced beta cell death by reexpressing this protein in MIN6 murine beta cells
      lacking caveolin-1. Incubation of MIN6 with palmitate, but not oleate, induced
      apoptotic cell death that was enhanced by the presence of caveolin-1. Moreover,
      palmitate induced de novo ceramide synthesis, loss of mitochondrial transmembrane
      potential and reactive oxygen species (ROS) formation in MIN6 cells. ROS
      generation promoted caveolin-1 phosphorylation on tyrosine-14 that was abrogated
      by the anti-oxidant N-acetylcysteine or the incubation with the Src-family kinase
      inhibitor, PP2 (4-amino-5-(4-chlorophenyl)-7(dimethylethyl)pyrazolo[3,4
      d]pyrimidine). The expression of a non-phosphorylatable caveolin-1 tyrosine-14 to
      phenylalanine mutant failed to enhance palmitate-induced apoptosis while for MIN6
      cells expressing the phospho-mimetic tyrosine-14 to glutamic acid mutant caveolin
      1 palmitate sensitivity was comparable to that observed for MIN6 cells expressing
      wild type caveolin-1. Thus, caveolin-1 expression promotes palmitate-induced ROS
      dependent apoptosis in MIN6 cells in a manner requiring Src family kinase
      mediated tyrosine-14 phosphorylation. 

PMID- 25572856
TI  - Protective effects of Lycium barbarum polysaccharides against carbon
      tetrachloride-induced hepatotoxicity in precision-cut liver slices in vitro and
      in vivo in common carp (Cyprinus carpio L.).
AB  - The protective effects of Lycium barbarum polysaccharides (LBPs) against carbon
      tetrachloride-induced hepatotoxicity in common carp were investigated in vitro
      and in vivo. Precision-cut liver slices (PCLSs) were employed as an in vitro
      model system. LBPs (0.1, 0.3 and 0.6 mg/ml) was added to PCLSs culture system
      before (pre-treatment), after (post-treatment) and both before and after (pre-
      and post-treatment) the exposure of PCLSs to 12 mM CCl4. The supernatants and
      PCLSs were collected for biochemical analyses. Results showed that LBPs inhibited
      the elevations of the marker enzymes (GOT, GPT, LDH and AKP) and MDA induced by
      CCl4 in all LBPs treatments and it also enhanced the suppressed antioxidant
      enzymes (SOD, CAT, GSH-Px, GST) and GSH, in the pre-treatment and pre- and post
      treatment. In vivo, fish were fed diets containing LBPs at 0.1, 0.5 and 1% for 60
      d before an intraperitoneal injection of 30% CCl4 in olive oil at a volume of
      0.05 ml/10 g body weight. At 72 h post-injection, blood and liver samples were
      taken for biochemical analyses. Results showed that LBPs at 0.5 and 1%
      significantly reduced the levels of GOT, GPT and LDH in the serum; the decreases
      of the antioxidant enzymes and the increase of MDA in the liver tissue were
      inhibited markedly. Moreover, LBPs even at lower concentration exerted a potent
      DPPH scavenging activity. Overall results prove the hepatoprotective and
      antioxidant effects of LBPs and support the use of LBPs as a hepatoprotective
      agent in fish.

PMID- 25572855
TI  - Neurotoxicological effects on marine mussel Mytilus galloprovincialis caged at
      petrochemical contaminated areas (eastern Sicily, Italy): 1H NMR and
      immunohistochemical assays.
AB  - The neurotoxicological potential of environmental pollution, mainly related to
      petrochemical activities, was investigated in marine mussel Mytilus
      galloprovincialis. Bivalve mollusks, particularly mussels, are widely used as
      sentinel organisms in biomonitoring studies for assessing the impact of
      anthropogenic contaminants. The gills, mainly involved in nutrient uptake,
      digestion, gas exchange and neuronal signaling, are the first organ to be
      affected by pollutants present in the external environment, and therefore were
      selected as the target organ for this study. Mussels from an aquaculture farm
      were caged at a highly polluted petrochemical area and a reference site along the
      Augusta coastline (eastern Sicily, Italy) for one month. A battery of biomarkers
      indicative of neuronal perturbations was applied on gills in order to investigate
      on the serotonergic (i.e. serotonin, 5-HT, and its receptor, 5-HT3R), cholinergic
      (i.e. acetylcholine, acetylcholinesterase, AChE, and choline acetyltransferase,
      ChAT), and dopaminergic systems (i.e. tyrosine and tyrosine hydroxylase, TH).
      Overall, impairment in the normal ciliary motility was found in mussels caged at
      the polluted site. Alterations in serotoninergic and cholinergic systems were
      revealed, with enhancement of dopaminergic neurotransmission resulting in a cilio
      inhibitory effect. However, the over-expression in 5-HT3R and ChAT at cellular
      level may indicate an adaptive response of mussels to recover a regular
      physiological activity in gills. To our knowledge, this is the first study that
      uses (1)H NMR and immunohistochemical assays. Their concurrent use demonstrated
      to be sensitive and effective for assessing environmental influences on the
      health status of aquatic organisms, and thus suitable to be applied in
      ecotoxicological studies. 

PMID- 25572857
TI  - Systemic toxic effects induced by the aqueous extract of the fire coral Millepora
      complanata and partial purification of thermostable neurotoxins with lethal
      effects in mice.
AB  - Millepora complanata is a cnidarian widely distributed in the coral reefs of the
      Mexican Caribbean. This species is popularly known as "fire coral", since contact
      with it causes severe pain, skin eruptions and blisters. Intravenous
      administration of of M. complanata aqueous extract induces violent convulsions
      and death in mice within 1 min (LD50=4.62ugprotein/g of body weight). Doses less
      than the LD50 produced histopathological damage in kidneys and lungs. Such
      histopathological damage was completely eliminated after incubation of the
      extract in heat denaturing conditions. Unexpectedly, the denatured extract
      conserved its lethal effect. These findings demonstrated that the extract
      contained hemolytic and phospholipase activities that might be responsible for
      the histopathological damage, and additionally it contained other unidentified
      thermostable toxins with lethal effects in mice. Chromatographic analysis of the
      extract led to the isolation of a 61 kDa vasoconstrictor protein. Furthermore,
      several non-peptidic vasoconstrictor fractions were separated. Particularly
      interesting was the fraction MC1-IIA obtained as a result of three-step
      chromatography processes (ion exchange, gel filtration and reverse phase). Like
      the original crude extract, this fraction induced vasoconstriction and delayed
      hemolysis and lethal effects in mice. A subsequent chromatographic analysis of
      MC1-IIA showed that this fraction contained at least four non-peptidic compounds.
      MS and NMR spectroscopic data analyses indicated that these metabolites were poly
      oxygenated alkylbenzenes. The present study constitutes the first report of the
      presence of non-peptidic lethal toxins in an organism of the class Hydrozoa, and
      evidences the great structural diversity of the toxins produced by the Millepora
      species.

PMID- 25572858
TI  - Congenital pericardial defect: a case of right pericardial partial absence with
      normal parietal pleura [corrected].
AB  - Congenital pericardial defect (CPD) is a rare cardiovascular anomaly. A right
      sided CPD is much rarer than left-sided defects. Usually both the pericardium and
      parietal pleura are absent. We report a rare case of a right partial CPD
      involving the right atrial appendage, suspected by computed tomography and cine
      magnetic resonance imaging, and confirmed by thoracoscopy, which also
      demonstrated a normal parietal pleura. 

PMID- 25572860
TI  - Aging resistance of surface-treated dental zirconia.
AB  - The influence of surface treatment on the low-temperature degradation (LTD) of
      tetragonal zirconia polycrystalline (TZP) is still unclear. OBJECTIVES: The
      effect of surface treatments on the LTD behavior of zirconia was investigated.
      METHODS: Fully-sintered specimens of seven commercial dental zirconia (Aadva, GC;
      In-CeramYZ, VITA; IPS e.max ZirCAD, Ivoclar Vivadent; LAVA Frame and LAVA Plus,
      3M ESPE; NANOZR, Panasonic; ZirTough, Kuraray Noritake) were provided by the
      manufacturers with specimen dimensions of approximately 10mm*5mm*3mm. For each
      zirconia grade, samples were kept 'as sintered' (untreated) or were subjected to
      one of the three surface treatments: rough polished, sandblasted with Al2O3,
      tribochemical silica sandblasted (n=3/group). The tetragonal to monoclinic
      transformation was evaluated by X-ray diffraction at several intervals during LTD
      testing up to 40h in steam in an autoclave (134 degrees C, 2bar). RESULTS: The
      five yttria-stabilized TZP (Y-TZP: Aadva, In-CeramYZ, IPS e.max ZirCAD, LAVA
      Frame, LAVA Plus) zirconia showed a similar trend in LTD behavior. The Al2O3
      sandblasted zirconia showed the highest monoclinic volume fraction. The as
      sintered (untreated) zirconia degraded faster than the surface-treated zirconia.
      Although the surface-treated ceria-stabilized TZP/alumina (Ce-TZP/Al2O3: NANOZR)
      zirconia had a higher initial monoclinic volume fraction compared to the Y-TZP
      zirconia, it showed a stronger aging resistance. The as sintered (untreated) Y
      TZP/alumina (Y-TZP/Al2O3: ZirTough) zirconia showed a strong aging resistance,
      whereas the surface-treated Y-TZP/Al2O3 zirconia degraded slightly. SIGNIFICANCE:
      Surface treatment improved the aging resistance of Y-TZP zirconia. Surface
      treatment did not affect the LTD behavior of Ce-TZP/Al2O3 zirconia, while surface
      treatment decreased the aging resistance of Y-TZP/Al2O3 zirconia.

PMID- 25572859
TI  - Acute immunomodulatory effects of binge alcohol ingestion.
AB  - BACKGROUND: Blood alcohol is present in a third of trauma patients and has been
      associated with organ dysfunction. In both human studies and in animal models, it
      is clear that alcohol intoxication exerts immunomodulatory effects several hours
      to days after exposure, when blood alcohol is no longer detectable. The early
      immunomodulatory effects of alcohol while blood alcohol is still elevated are not
      well understood. METHODS: Human volunteers achieved binge alcohol intoxication
      after high-dose alcohol consumption. Blood was collected for analysis prior to
      alcohol ingestion, and 20 min, 2 h, and 5 h after alcohol ingestion. Flow
      cytometry was performed on isolated peripheral blood mononuclear cells, and
      cytokine generation in whole blood was measured by enzyme-linked immunosorbent
      assay (ELISA) after 24-h stimulation with lipopolysaccharide (LPS) and
      phytohemagglutinin-M (PHA) stimulation. RESULTS: An early pro-inflammatory state
      was evident at 20 min when blood alcohol levels were ~130 mg/dL, which was
      characterized by an increase in total circulating leukocytes, monocytes, and
      natural killer cells. During this time, a transient increase in LPS-induced tumor
      necrosis factor (TNF)-alpha levels and enhanced LPS sensitivity occurred. At 2
      and 5 h post-alcohol binge, an anti-inflammatory state was shown with reduced
      numbers of circulating monocytes and natural killer cells, attenuated LPS-induced
      interleukin (IL)-1beta levels, and a trend toward increased interleukin (IL)-10
      levels. CONCLUSIONS: A single episode of binge alcohol intoxication exerted
      effects on the immune system that caused an early and transient pro-inflammatory
      state followed by an anti-inflammatory state.

PMID- 25572866
TI  - Pre-radiotherapy feeding tube identifies a poor prognostic subset of
      postoperative p16 positive oropharyngeal carcinoma patients.
AB  - BACKGROUND: This study explores variables associated with poor prognosis in
      postoperative p16 positive oropharyngeal squamous cell carcinoma (OPSCC) patients
      undergoing adjuvant radiotherapy or chemoradiotherapy. Specifically, analysis was
      done related to timing of feeding tube insertion relative to radiotherapy.
      METHODS: From 1997-2009, of 376 consecutive patients with OPSCC, 220 received
      adjuvant IMRT, and 97 were p16 positive and eligible. Of these, 23 had feeding
      tube placement before IMRT (B-FT), 32 during/after IMRT (DA-FT), and 42 had no
      feeding tube (NO-FT). Feeding tubes were not placed prophylactically. These three
      groups were analyzed for differential tumor, patient, treatment, and feeding tube
      characteristics, as well as differences in overall survival (OS), disease free
      survival (DFS), and distant metastasis free survival (DMFS). RESULTS: Pre-RT FT
      insertion was associated with higher tumor size and depth, T (but not N) and
      overall stage, comorbidities, presence of chemotherapy, and less use of transoral
      laser microsurgery/transoral bovie. Additionally, time from surgery to IMRT
      completion was also statistically longer in the B-FT group. The feeding tube was
      permanent in 52% of patients in the B-FT group versus 16% in the DA-FT group (p =
      0.0075). The 5-year OS for the NO-FT, DA-FT, and B-FT groups was 90%, 86%, and
      50%, respectively. The 5-year DFS for the NO-FT, DA-FT, and B-FT groups was
      87.6%, 83.6%, and 42.7%, respectively. Multivariate analysis showed that for OS
      and DFS, feeding tube placement timing and smoking history were statistically
      significant. CONCLUSION: Due to the poor prognosis of early FT insertion, the
      presence of FTs at time of radiotherapy consultation can be used as an alternate
      marker to identify a subset of p16 positive OPSCC patients that have a poor
      prognosis.

PMID- 25572867
TI  - Protective effect of delta-amyrone against ethanol-induced gastric ulcer in mice.
AB  - The purpose of this study is to examine the protective effect of delta-amyrone on
      ethanol-induced gastric ulcer in mice. The mice intragastric administration 75%
      (0.5 mL/100g) ethanol was pretreated with delta-amyrone (4 and 8 mg/kg) and
      cimetidine (100 mg/kg) or vehicles in different experimental groups for a
      continuous three-day, and animals were euthanized 3h after ethanol ingestion. The
      gastric lesions were significantly attenuated by delta-amyrone (4 and 8 mg/kg) as
      compared to the ulcer control group. Pre-treatment with delta-amyrone prevented
      the myeloperoxidase (MPO) activity, production of nitric oxide (NO) in serum,
      expression of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B
      (NF-kappaB) p65 protein expression. Analysis of cytokines in gastric tissue and
      serum of ethanol-induced mice showed the levels of tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-6 (IL-6) were decreased by delta-amyrone in response
      to NF-kappaB p65. These results suggested that delta-amyrone exerts its
      protective effect on experimental gastric ulcer by inhibiting NF-kappaB signaling
      pathways, which subsequently reduces overproduction of the inducible enzymes iNOS
      and suppresses the release of the inflammatory factors TNF-alpha, IL-6 and NO.
      Thus, delta-amyrone shows promise as a therapeutic agent in experimental gastric
      ulcer.

PMID- 25572868
TI  - Evaluating change in symptomatic and functional level of children and youth with
      emotional disorders: a naturalistic observation study.
AB  - The objective of the study is to describe the changes in symptomatic and
      functional impairment for children and youth with emotional disorders treated at
      child and adolescent mental health outpatient services (CAMHS) in Norway. The
      study was of naturalistic observational type in which the treatment can be
      classified as "treatment as usual" (TAU). The Strengths and Difficulties
      Questionnaire (SDQ), the Health of the Nation Outcome Scale (HONOSCA) and the
      Children's Global Assessment Scale (CGAS) were used as measures of change. The
      information from multiple informants allowed the evaluation of change from
      different perspectives. The sample consisted of 84 children and youth with
      emotional disorders treated at two CAMHS in the North of Norway. The SDQ, the
      HONOSCA and the CGAS were administered at intake (T0), during assessment (T1) and
      approximately, 6 months after T1 (T2). Change was analysed by means of the Linear
      Mixed Models procedure. The results show that children and youth with emotional
      disorders experience a statistically significant improvement per month during
      outpatient treatment according to nearly all the measures of change. For the
      clinician rated scores, change rates during active assessment/treatment were
      larger than during the waitlist period. Evaluating change from the perspective of
      clinical significance showed that only a small proportion of the subjects had
      change scores that were statistically reliable and clinically significant.
      Whether an actual change has occurred is uncertain for the majority of patients. 

PMID- 25572870
TI  - Berberine inhibits the proliferation of prostate cancer cells and induces G0/G1
      or G2/M phase arrest at different concentrations.
AB  - Prostate cancer is the second most common disease of the male reproductive
      system. Berberine is a quaternary ammonium salt that is extracted from plants.
      The aim of the current study was to explore the antitumor activity of berberine
      in prostate cancer cells and identify the underlying mechanism of its effects.
      PC3 human and RM-1 mouse prostate cancer cells were treated with increasing
      concentrations of berberine, followed by analysis of the cell viability with an
      MTT assay. The results demonstrated that berberine markedly inhibited the
      proliferation of PC3 and RM-1 cells, and that the inhibitory effects to PC3 and
      RM-1 were enhanced in a concentration- and time-dependent manner. Flow cytometry
      was used to analyze the cell cycle of PC3 human prostate cancer cells, and the
      results demonstrated that G0/G1 phase arrest was induced following treatment with
      10 uM berberine (P<0.05). However, with an increased concentration of berberine
      (50 uM) the survival rate of PC3 cells at the G2/M phase was significantly
      increased compared with the cells treated with 10 uM berberine, which suggests
      that different cell cycle signaling pathways were activated when PC3 cells were
      treated with low and high concentrations of berberine. Thus, clarifying the
      mechanism underlying these effects in prostate cancer may provide novel molecular
      targets for prostate cancer therapy.

PMID- 25572869
TI  - The emotional-behavioural functioning of children exposed to maternal depressive
      symptoms across pregnancy and early childhood: a prospective Australian pregnancy
      cohort study.
AB  - Children exposed to maternal depression during pregnancy and in the postnatal
      period are at increased risk of a range of health, wellbeing and development
      problems. However, few studies have examined the course of maternal depressive
      symptoms in the perinatal period and beyond on children's wellbeing. The present
      study aimed to explore the relationship between both the severity and chronicity
      of maternal depressive symptoms across the early childhood period and children's
      emotional-behavioural difficulties at 4 years of age. Data from over 1,085
      mothers and children participating in a large Australian prospective pregnancy
      cohort were used. Latent class analysis identified three distinct trajectories of
      maternal depressive symptoms from pregnancy to 4 years postpartum: (1) no or few
      symptoms (61%), (2) persistent subclinical symptoms (30%), and (3) increasing and
      persistently high symptoms (9%). Regression analyses revealed that children of
      mothers experiencing subclinical and increasing and persistently high symptoms
      were at least two times more likely to have emotional-behavioural difficulties
      than children of mothers reporting minimal symptoms, even after accounting for
      known risk factors for poor outcomes for children. These findings challenge
      policy makers and health professionals to consider how they can tailor care and
      support to mothers experiencing a broader spectrum of depressive symptoms across
      the early childhood period, to maximize opportunities to improve both short-and
      long-term maternal and child health outcomes.

PMID- 25572871
TI  - Hydrophilic polymer monolithic capillary microextraction online coupled to ICPMS
      for the determination of carboxyl group-containing gold nanoparticles in
      environmental waters.
AB  - In this study, the hydrophilic polymer monolithic capillary (poly(acrylamide
      vinylpyridine-methylene bis(acrylamide)), poly(AA-VP-Bis)) was prepared for the
      separation and enrichment of carboxyl group-containing gold nanoparticles (Au
      NPs) from environmental waters followed by online ICPMS determination. The
      extraction mechanism of the prepared poly(AA-VP-Bis) monolithic capillary for Au
      NPs is based on the static electrical and hydrogen bond interactions between the
      carboxyl group on the surface of Au NPs and pyridine/amide groups on the surface
      of the monolith. Under the optimal conditions, a detection limit of 24.2 fmol L(
      1) and a sample throughput of 6 h(-1) were achieved for 3 nm citrate stabilized
      Au NPs, and the original morphology of the Au NPs could be maintained during the
      extraction process. The developed method was successfully applied for the
      analysis of carboxyl group-containing Au NPs in environmental water samples, such
      as tap water, the Yangtze River water, and the East Lake water, with recoveries
      in the range of 77-103%. Compared with the reported approaches for analysis of Au
      NPs, this method is an online strategy for carboxyl group-containing Au NPs
      determination and has the merits of low detection limit, small sample
      consumption, fast extraction/desorption kinetics, wide linear range, high
      selectivity, and high throughput. 

PMID- 25572872
TI  - In vitro maturation of oocytes is not associated with altered deoxyribonucleic
      acid methylation patterns in children from in vitro fertilization or
      intracytoplasmic sperm injection.
AB  - OBJECTIVE: To study the possible transmission, to the next generation, of
      epigenetic defects associated with in vitro maturation (IVM) of human oocytes.
      DESIGN: Case-control study using epigenetic data. SETTING: Two collaborating
      university departments. PATIENT(S): Eleven IVM newborns and 19 controls,
      conceived by conventional assisted reproduction. INTERVENTION(S): Chorionic
      villus and cord-blood sampling. MAIN OUTCOME MEASURE(S): Using bisulfite
      pyrosequencing, we have measured average methylation levels of 6 imprinted (LIT1,
      MEG, MEST, NESPas, PEG3, and SNRPN), 5 tumor-suppressor (APC, ATM, BRCA1, RAD51C,
      and TP53), 2 pluripotency (NANOG and OCT4), and 2 metabolic (LEP and NR3C1)
      genes, as well as 2 repetitive elements (ALU and LINE1) in 2 tissues of IVM and
      control neonates. Using deep bisulfite sequencing, we have determined methylation
      patterns of many individual DNA molecules to detect rare RAD51C epimutations
      (allele methylation errors). RESULT(S): No statistically significant impact was
      found of IVM on chorionic villus and cord-blood DNA methylation at the studied
      developmentally important genes and interspersed repeats. The RAD51C epimutation
      rate was low (0.5% +/- 0.1%) in all analyzed samples. CONCLUSION(S): IVM-induced
      epigenetic changes in offspring, if any, are relatively small in magnitude and/or
      infrequent.

PMID- 25572874
TI  - In vitro development of donated frozen-thawed human embryos in a prototype static
      microfluidic device: a randomized controlled trial.
AB  - OBJECTIVE: To compare the development of human embryos in microfluidic devices
      with culture in standard microdrop dishes, both under static conditions. DESIGN:
      Prospective randomized controlled trial. SETTING: In vitro fertilization
      laboratory. PATIENT(S): One hundred eighteen donated frozen-thawed human day-4
      embryos. INTERVENTION(S): Random allocation of embryos that fulfilled the
      inclusion criteria to single-embryo culture in a microfluidics device (n = 58) or
      standard microdrop dish (n = 60). MAIN OUTCOME MEASURE(S): Blastocyst formation
      rate and quality after 24, 28, 48, and 72 hours of culture. RESULT(S): The
      percentage of frozen-thawed day-4 embryos that developed to the blastocyst stage
      did not differ significantly in the standard microdrop dishes and microfluidic
      devices after 28 hours of culture (53.3% vs. 58.6%) or at any of the other time
      points. The proportion of embryos that would have been suitable for embryo
      transfer was comparable after 28 hours of culture in the control dishes and
      microfluidic devices (90.0% vs. 93.1%). Furthermore, blastocyst quality was
      similar in the two study groups. CONCLUSION(S): This study shows that a
      microfluidic device can successfully support human blastocyst development in
      vitro under static culture conditions. Future studies need to clarify whether
      earlier stage embryos will benefit from the culture in microfluidic devices more
      than the tested day-4 embryos because many important steps in the development of
      human embryos already take place before day 4. Further improvements of the
      microfluidic device will include parallel culture of single embryos, application
      of medium refreshment, and built-in sensors. DUTCH TRIAL REGISTRATION NUMBER:
      NTR3867.

PMID- 25572873
TI  - Ultrasound features of polycystic ovaries relate to degree of reproductive and
      metabolic disturbance in polycystic ovary syndrome.
AB  - OBJECTIVE: To reexamine associations between polycystic ovarian morphology (PCOM)
      and degree of symptomatology in polycystic ovary syndrome (PCOS) using a well
      defined PCOS population, newer ultrasound technology, and reliable offline
      assessments of sonographic parameters. DESIGN: Cross-sectional observational
      study. SETTING: Academic hospital and clinical research unit. PATIENT(S): Forty
      nine women with PCOS as defined by hyperandrogenism and oligoamenorrhea.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of follicles per follicle
      size category, antral follicle count (AFC), ovarian volume (OV), follicle
      distribution pattern, stromal area, ovarian area, stromal to ovarian area ratio
      (S/A) and stromal echogenicity index (SI), total (TT), androstenedione, LH, FSH,
      cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, C
      reactive protein, glucose, insulin, and hemoglobin A1C, menstrual cycle length,
      hirsutism score, body mass index (BMI), waist:hip ratio, and blood pressure.
      RESULT(S): AFC, but not OV, was positively associated with TT (rho = .610),
      androstenedione (rho = .490), and LH:FSH (rho = .402). SI was positively
      associated with androgen markers and LH:FSH, while S/A was negatively associated
      with these variables. Follicles <=4 mm were negatively associated with various
      metabolic markers, whereas larger follicles (5-8 mm) showed positive
      associations. Stromal markers were not associated with cardiometabolic measures.
      LH:FSH best predicted follicles <=4 mm, and BMI predicted 5- to 9-mm follicles.
      Dominant follicles >=10 mm were best predicted by age. CONCLUSION(S): AFC, and
      not OV, reflected the severity of reproductive dysfunction in PCOS. Associations
      among different sized follicles were consistent with recruitable sized follicles,
      which reflects the severity of metabolic dysfunction in PCOS.

PMID- 25572875
TI  - Interleukin-1beta increases permeability and upregulates the expression of
      vascular endothelial-cadherin in human renal glomerular endothelial cells.
AB  - The renal glomerular capillary endothelium is part of the glomerular filtration
      barrier and is involved in acute and chronic inflammation of the glomerulus.
      Glomerular endothelial cells are a unique type of microvascular cell, which
      remain to be fully characterized. The aim of the present study was to examine the
      permeability of glomerular endothelial cells and their responses to interleukin
      (IL)-1beta, a pro-inflammatory cytokine. Human glomerular endothelial cell
      (HRGEC) and human umbilical vein endothelial cell (HUVEC) monolayers were
      examined using a Transwell permeability assay, transendothelial electrical
      resistance (TEER) and by determining the expression of the adhesion molecule,
      vascular endothelial (VE)-cadherin, in the absence or presence of 10 ng/ml IL
      1beta. Compared with the HUVECs, the HRGECs demonstrated higher permeability,
      lower TEER and reduced expression of VE-cadherin. IL-1beta induced an increase in
      the permeability and a decrease in the TEER of the HRGECs, however, to a lesser
      extent compared with the HUVECs. Following IL-1beta treatment, the expression of
      VE-cadherin was increased in the HRGECs and decreased in the HUVECs. These
      results suggested that HRGECs have distinct biological properties and specific
      gene expression features in response to IL-1beta.

PMID- 25572876
TI  - Production of stable isotope-labeled acyl-coenzyme A thioesters by yeast stable
      isotope labeling by essential nutrients in cell culture.
AB  - Acyl-coenzyme A (CoA) thioesters are key metabolites in numerous anabolic and
      catabolic pathways, including fatty acid biosynthesis and beta-oxidation, the
      Krebs cycle, and cholesterol and isoprenoid biosynthesis. Stable isotope dilution
      based methodology is the "gold standard" for quantitative analyses by mass
      spectrometry. However, chemical synthesis of families of stable isotope-labeled
      metabolites such as acyl-CoA thioesters is impractical. Previously, we
      biosynthetically generated a library of stable isotope internal standard analogs
      of acyl-CoA thioesters by exploiting the essential requirement in mammals and
      insects for pantothenic acid (vitamin B5) as a metabolic precursor for the CoA
      backbone. By replacing pantothenic acid in the cell medium with commercially
      available [(13)C3(15)N1]-pantothenic acid, mammalian cells exclusively
      incorporated [(13)C3(15)N1]-pantothenate into the biosynthesis of acyl-CoA and
      acyl-CoA thioesters. We have now developed a much more efficient method for
      generating stable isotope-labeled CoA and acyl-CoAs from [(13)C3(15)N1]
      pantothenate using stable isotope labeling by essential nutrients in cell culture
      (SILEC) in Pan6-deficient yeast cells. Efficiency and consistency of labeling
      were also increased, likely due to the stringently defined and reproducible
      conditions used for yeast culture. The yeast SILEC method greatly enhances the
      ease of use and accessibility of labeled CoA thioesters and also provides proof
      of concept for generating other labeled metabolites in yeast mutants. 

PMID- 25572877
TI  - The impact of understaffed shifts on nurse-sensitive outcomes.
AB  - AIM: To explore the relationship between exposure to understaffed shifts and
      nurse-sensitive outcomes at the patient level. BACKGROUND: Nurse-sensitive
      outcomes are adverse patient outcomes that can be used as indicators of the
      quality of nursing care. DESIGN: This study was conducted in 2014 and was a
      secondary analysis of administrative data from a large acute care hospital in
      Western Australia. The sample included 36,529 patient admissions over a two-year
      period from October 2004-November 2006. METHODS: An understaffed indicator
      variable was created from nurse staffing data and used to examine patient data to
      create a variable indicating the total number of understaffed shifts each patient
      had been exposed to during their hospital stay. Logistic regression was used to
      determine the odds of acquiring a nurse-sensitive outcome for those exposed to
      understaffed shifts. RESULTS: The prevalence ratio showed that for each of the
      nurse-sensitive outcomes there was an increase in prevalence for those who were
      exposed to an understaffed shift, with all ratios being greater than one. After
      adjusting for patient characteristics, nurse-sensitive outcomes found to have the
      understaffed variable significant in the logistic regression model were surgical
      wound infection, urinary tract infection, pressure injury, pneumonia, deep vein
      thrombosis, upper gastrointestinal bleed, sepsis and physiological metabolic
      derangement. All odds ratios were small effects. CONCLUSION: Preventing
      understaffing is a consideration for improving the quality of care for patients.
      Attributing the understaffing variable at the patient level enables exposure to
      be captured across ward changes increasing the sensitivity with which this
      variable can be measured.

PMID- 25572878
TI  - The Charite cesarean birth: a family orientated approach of cesarean section.
AB  - OBJECTIVE: To evaluate the safety and patients delivery experience of the Charite
      Cesarean Birth (CCB), a modified cesarean section (CS). Parents are actively
      integrated in the delivery process by direct visualization of the birth, cutting
      the umbilical cord and early skin-to-skin contact (STS). METHODS: Women with an
      indication for a planned primary CS at term were included. Trial was conducted at
      the Charite University Hospital Berlin as a prospectively randomized controlled
      trial. Parameters of perinatal outcome for both mother and infant were assessed
      using modified Likert-Scales and a standardized questionnaire. Primary outcome
      measures were birth experience and satisfaction for parents. Parameters of breast
      feeding and consecutive problems. APGAR Scores, blood loss, perioperative
      complications were secondary outcome measures. RESULTS: Birth experiences were
      rated significantly higher in the CCB group compared to a classical caesarean
      section (p < 0.05). There were no significant differences between APGAR Scores,
      need for admission to an intensive care unit. Also perioperative blood loss and
      cardiovascular disorders did not differ between the two groups. Early STS was
      achieved in the 72% of the cases with higher rates of breast-feeding in the CCB
      group. CONCLUSIONS: The CCB leads to a significantly better birth experience. The
      procedure seems to be safe for both mother and infant. Patients become an active
      part of the CS by direct visualization of the birth and cutting the umbilical
      cord. The presented modification is a useful and safe option when a CS is
      medically indicated and necessary. It improves the breast-feeding and the early
      mother-infant interaction.

PMID- 25572879
TI  - Permanently compromised NADPH-diaphorase activity within the osmotically
      activated supraoptic nucleus after in utero but not adult exposure to Aroclor
      1254.
AB  - Stimulated vasopressin (VP) release from magnocellular neuroendocrine cells in
      the supraoptic nucleus (SON) of hyperosmotic rats is inhibited by treatment with
      the industrial polychlorinated biphenyl (PCB) mixture, Aroclor 1254. Because VP
      responses to hyperosmotic stimulation are regulated by nitric oxide (NO)
      signaling, we studied NO synthase (NOS) activity in the SON of hyperosmotic rats
      as potential target of PCB-induced disruption of neuroendocrine processes
      necessary for osmoregulation. To examine PCB-induced changes in NOS activity
      under normosmotic and hyperosmotic conditions, male Sprague-Dawley rats were
      exposed to Aroclor 1254 (30mg/kg/day) in utero and NADPH-diaphorase (NADPH-d)
      activity was assessed in SON sections at three ages: postnatal day 10, early
      adult (3-5 months) or late adult (14-16 months). Hyperosmotic treatment increased
      mean NADPH-d staining density of oil hyperosmotic controls by 19.9% in early
      adults and 58% in late adulthood vs normosmotic controls. In utero exposure to
      PCBs reduced hyperosmotic-induced upregulation of NADPH-d activity to control
      levels in early adults and by 28% in late adults. Basal NADPH-d was reduced in
      postnatal rats. Rats receiving PCB exposure as early adults orally for 14 days
      displayed normal responses. Our findings show that developmental but not adult
      exposure to PCBs significantly reduces NOS responses to hyperosmolality in
      neuroendocrine cells. Moreover, reduced NADPH-d activity produced by in utero
      exposure persisted in stimulated late adult rats concomitant with reduced
      osmoregulatory capacity vs oil controls (375+/-9 vs 349+/-5mOsm/L). These
      findings suggest that developmental PCBs permanently compromise NOS signaling in
      the activated neuroendocrine hypothalamus with potential osmoregulatory
      consequences. 

PMID- 25572880
TI  - Prenatal p,p'-DDE exposure and establishment of lateralization and spatial
      orientation in Mexican preschooler.
AB  - BACKGROUND: Prenatal exposure to p,p'-DDE is associated with impairments in motor
      development during the first year of life, with no related repercussions on
      mental or motor development at 12-30 months and with impairments in cognitive
      areas, but not in perceptual and motor areas at preschool age. However, its
      association with particular psychomotor factors, such as establishment of
      lateralization and spatial orientation, essential elements to the overall
      learning and specifically reading, writing and spelling in preschoolers, has not
      been independently evaluated, since cognitive and motor areas have only been
      explored globally. OBJECTIVE: To determine the association between prenatal
      exposure to p,p'-DDE and the establishment of lateralization and spatial
      orientation in children 5 years of age. MATERIALS AND METHODS: Establishment of
      lateralization and spatial orientation was evaluated using the McCarthy Scale of
      Children's Abilities, with 167 children 5 years of age who participated in a
      birth cohort in the state of Morelos, Mexico. The information available for each
      child included: serum concentrations of p,p'-DDE of the mother during at least
      one trimester of pregnancy, mothers' intelligence quotients, stimulation at home
      and anthropometry. A logistic regression model was used to calculate the
      association between prenatal exposure to p,p'-DDE and lateralization and a
      multiple linear regression model was used for the association with spatial
      orientation. RESULTS: A two-fold increase in p,p'-DDE in lipid base during the
      second trimester of pregnancy was associated with a significant reduction, -0.18
      points (95% CI -0.41; 0.04, in the spatial orientation index, with no impairment
      in the establishment of hemispheric dominance. Attending preschool and the
      maternal intelligence quotient were the main determinants of spatial orientation
      and the establishment of hemispheric dominance. CONCLUSIONS: Prenatal exposure to
      p,p'-DDE may affect the 5 year old's ability to identify spatial orientation of
      oneself and surrounding objects. Given the observed role of attending preschool
      in the functions studied, early attendance in formal education might serve as a
      stimulation strategy for preschoolers. These preliminary results should be
      verified and expanded in further prospective studies with DDE.

PMID- 25572882
TI  - Bats as 'special' reservoirs for emerging zoonotic pathogens.
AB  - The ongoing West African Ebola epidemic highlights a recurring trend in the
      zoonotic emergence of virulent pathogens likely to come from bat reservoirs that
      has caused epidemiologists to ask 'Are bats special reservoirs for emerging
      zoonotic pathogens?' We collate evidence from the past decade to delineate
      mitochondrial mechanisms of bat physiology that have evolved to mitigate
      oxidative stress incurred during metabolically costly activities such as flight.
      We further describe how such mechanisms might have generated pleiotropic effects
      responsible for tumor mitigation and pathogen control in bat hosts. These
      synergisms may enable 'special' tolerance of intracellular pathogens in bat
      hosts; paradoxically, this may leave them more susceptible to immunopathological
      morbidity when attempting to clear extracellular infections such as 'white-nose
      syndrome' (WNS). 

PMID- 25572881
TI  - Virological features associated with the development of broadly neutralizing
      antibodies to HIV-1.
AB  - The development of a preventative HIV-1 vaccine remains a global public health
      priority. This will likely require the elicitation of broadly neutralizing
      antibodies (bNAbs) able to block infection by diverse viral strains from across
      the world. Understanding the pathway to neutralization breadth in HIV-1 infected
      humans will provide insights into how bNAb lineages arise, a process that
      probably involves a combination of host and viral factors. Here, we focus on the
      role of viral characteristics and evolution in shaping bNAbs during HIV-1
      infection, and describe how these findings may be translated into novel vaccine
      strategies.

PMID- 25572883
TI  - Mx GTPases: dynamin-like antiviral machines of innate immunity.
AB  - The Mx dynamin-like GTPases are key antiviral effector proteins of the type I and
      type III interferon (IFN) systems. They inhibit several different viruses by
      blocking early steps of the viral replication cycle. We focus on new structural
      and functional insights and discuss recent data revealing that human MxA (MX1)
      provides a safeguard against introduction of avian influenza A viruses (FLUAV)
      into the human population. The related human MxB (MX2) serves as restriction
      factor for HIV-1 and other primate lentiviruses. 

PMID- 25572884
TI  - gEM/GANN: A multivariate computational strategy for auto-characterizing
      relationships between cellular and clinical phenotypes and predicting disease
      progression time using high-dimensional flow cytometry data.
AB  - The dramatic increase in the complexity of flow cytometric datasets requires new
      computational approaches that can maximize the amount of information derived and
      overcome the limitations of traditional gating strategies. Herein, we present a
      multivariate computational analysis of the HIV-infected flow cytometry datasets
      that were provided as part of the FlowCAP-IV Challenge using unsupervised and
      supervised learning techniques. Out of 383 samples (stimulated and unstimulated),
      191 samples were used as a training set (34 individuals whose disease did not
      progress, and 157 individuals whose disease did progress). Using the results from
      the training set, the participants in the Challenge were then asked to predict
      the condition and progression time of the remaining individuals (45
      "nonprogressors" and 147 "progressors"). To achieve this, we first scaled down
      data resolution and then excluded doublet cells from the analysis using
      Expectation Maximization approaches. We then standardized all samples into
      histograms and used Genetic Algorithm-Neural Network to extract feature sets from
      the datasets, the reliability of which were examined using WEKA-implemented
      classifiers. The selected feature set resulted in a high sensitivity and
      specificity for the discrimination of progressors and nonprogressors in the
      training set (average True Positive Rate = 1.00 and average False Positive Rate =
      0.033). The capacity of the feature set to predict real-time survival time was
      better when using data from the "unstimulated" training set (r = 0.825). The P
      values and 95% confidence interval log-rank ratios between actual and predicted
      survival time in the test set were 0.682 and 0.9542 +/- 0.24 for the unstimulated
      dataset, and 0.4451 and 0.9173 +/- 0.23 for the stimulated dataset. Our analytic
      strategy has demonstrated a promising capacity to extract useful information from
      complex flow cytometry datasets, despite a significance imbalance and variation
      between the training and test sets.

PMID- 25572885
TI  - A biomechanical evaluation of skull-brain surrogates to blunt high-rate impacts
      to postmortem human subjects.
AB  - The field of forensic injury biomechanics is an emerging field. Biomechanically
      validated tools may assist interdisciplinary teams of investigators in assessing
      mechanisms of blunt head trauma resulting in skull fractures. The objective of
      this study is to assess the biofidelity of spherical, frangible skull-brain (SB)
      surrogates. Blunt impacts were conducted at 20 m/s, using an instrumented 103 g
      rigid impactor, to the temporo-parietal region of four defleshed cephalic
      postmortem human subjects (PMHS). Force-deformation response, fracture tolerance,
      and fracture patterns were recorded for comparison to spherical skull-brain
      surrogates. Three brain substitutes were assessed: 10% gelatin, lead shot with
      Styrofoam and water. Force-deformation response of the skull-brain surrogates was
      similar to defleshed PMHS up to the point of fracture; however, none of the
      surrogates fractured at tolerance levels comparable to the PMHS. Fracture
      patterns of the skull-brain surrogates were linear and radiating, while PMHS
      fractures were all depressed, comminuted. 

PMID- 25572886
TI  - [Lay further emphasis on the cosmetic repair of deep burn wounds in extraordinary
      regions or caused by uncommon agents].
AB  - Along with the vigorous development of medical science and other related
      subjects, a lot of new techniques, concepts, materials, and methods continuously
      sprung up. The techniques of plastic and cosmetic surgery have already been used
      to repair burn wound at the early stage, especially to those wounds in
      extraordinary regions or caused by uncommon agents. These advances made burn
      wound treatment change from simply covering wound to save the patient's life to
      repairing wound and reconstructing function at the same time, which might achieve
      the aim of cosmetic repair in the future. Because of the hard work of burn
      surgeons, some progresses on the cosmetic repair of deep burn wounds in
      extraordinary regions or caused by uncommon agents have been achieved, but there
      is still a long way to go for the aim of cosmetic repair. Clinical practice has
      proved that as long as the basic principles of cosmetic repair are followed, the
      techniques and methods of plastic and cosmetic surgery are employed correctly,
      and the role of burn rehabilitation is highly emphasized, it is practicable to
      achieve cosmetic repair of deep burn wounds in extraordinary regions or caused by
      uncommon agents.

PMID- 25572887
TI  - [Treatment should be individualized for burn injury in extraordinary regions or
      caused by uncommon agents].
AB  - Burn wounds in extraordinary regions or caused by uncommon agents need
      individualized treatment according to their individual particularity. A perusal
      of papers to be published in this issue showed that most of burn units have paid
      attention to burn injuries pertaining to this category in their regular
      performance, and individualized treatment has been advocated. Accordingly, the
      treatment result of burns of this category has been improved. Furthermore,
      aesthetic and functional recovery has also been emphasized, thus the quality of
      life of the victim has been improved evidently, and they are able to return to
      family and society early.

PMID- 25572888
TI  - [Opportune time and method of reconstruction of penile defects caused by
      devastating electrical burn].
AB  - OBJECTIVE: To explore the timing and suitable method of reconstructing penile
      defects caused by devastating electrical burn. METHODS: Thirteen patients with
      penile defects after devastating electrical burn, hospitalized from September
      1998 to August 2013, were included in this study. After the necrotic tissues in
      the wounds were removed by dressing changes, a local or a hinge-like flap
      constructed from scrotum or abdominal wall, a prelaminated hinge-like flap from
      forearm, or a free forearm flap was selected, according to the injury degree of
      the penis, for the repair of the defect or reconstruction of penis respectively.
      RESULTS: The flaps survived and the wounds healed well in 2 patients repaired
      with local flaps from scrotum or abdominal wall. Urethritis occurred in 2
      patients 6 to 9 months after the transplantation of hinge-like flaps from
      scrotum, and they were cured by appropriate drugs. Functions of urination and
      erection of penis were recovered in these 4 patients. All flaps survived in the 5
      patients repaired with hinge-like flaps from abdominal wall or prelaminated flaps
      from forearm. The wounds in 2 patients healed; wound dehiscence occurred in the
      other 3 patients in different degrees, and they healed after suturing for 2 or 3
      times. The function of erection of penis recovered in these 5 patients, but with
      discontinuity of urinary stream during urination. Among them, 3 married patients
      enjoyed satisfactory sexual life. All free forearm flaps survived and the wounds
      healed well in 4 patients. Urinary fistula occurred in 1 patient, and it was
      repaired by a secondary operation. These 4 patients experienced normal urination
      function, but only 2 patients in whom corpus spongiosum partially remained
      retained the function of erection of penis to certain degree. All these 4
      patients could not perform normal sexual intercourse. All patients were followed
      up for 6 to 13 months after surgery. Under ordinary state, the length of penis
      was 5.9-9.3 cm, and the circumference of penis was 8.4-10.0 cm. Wound scar was
      not obvious in all cases. Nine patients reported a restricted erection.
      CONCLUSIONS: Penile defect caused by devastating electrical burn should be
      repaired with a suitable flap after necrotic tissues are removed with dressing
      change. To repair affected penis with necrosis of a small part of cavernous body
      and/or corpus spongiosum, or combined with urethra defects, local flaps from
      scrotum or abdominal wall or hinge-like flap from scrotum should be employed. To
      repair those with necrosis of a large part or the whole of corpus spongiosum
      combined with urethra defects, hinge-like skin flaps from abdominal wall or
      prelaminated flaps from forearm should be employed. In patients with necrosis of
      a large part of cavernous body and corpus spongiosum combined with urethra
      defect, or total loss of penis, free forearm flaps should be employed to
      reconstruct penis.

PMID- 25572889
TI  - [Analysis of clinical characteristics of 443 patients with inhalation injury].
AB  - OBJECTIVE: To explore the epidemiological characteristics of inhalation injury
      and to summarize the clinical application experience of diagnostic standard of
      burn of larynx. METHODS: Medical records of 443 patients with inhalation injury
      admitted to our burn unit from January 1999 to June 2013 were analyzed, including
      gender, age, severity of inhalation injury, complications and diseases before
      injury; total area and that of full-thickness burn injury, admission time after
      burn, and burn condition of larynx of patients with different degrees of
      inhalation injury; treatment and outcome including rate, time, and complication
      of tracheotomy, mortality, and cause of death. Data were processed with
      nonparametric Kruskal-Wallis test and chi-square test. The relationship between
      severity of inhalation injury and total burn area, degree of burn of larynx,
      tracheotomy rate, and mortality was assessed by Spearman correlation analysis.
      RESULTS: (1) Among the patients, there were 353 (79.7% ) male and 90 (20.3% )
      female, with the ratio of male to female 4:1. There were 64 (14.4%) patients
      younger than or equal to 20 years, 203 (45.8%) patients older than 20 years and
      younger than or equal to 40 years, 144 (32.5%) patients older than 40 years and
      younger than or equal to 60 years, and 32 (7.2%) patients older than 60 years.
      The numbers of patients with mild, moderate, and severe inhalation injury were
      respectively 297, 108, and 38. Seven patients suffered from complications, and 21
      patients had diseases before injury. There were statistically significant
      differences among the patients with different degree of inhalation injury in
      regard to total burn area and full-thickness burn area (with H values
      respectively 73.752 and 142.830, P values below 0.01), while no statistically
      significant difference was observed in admission time after burn ( H = 1.528, P >
      0.05). Correlation analysis showed that severity of inhalation injury was
      positively correlated with total burn area (r = 0.399, P < 0.001). Among the
      patients with mild inhalation injury, incidences of patients with mild, moderate,
      and severe burn of larynx were respectively 68.0% (202/297), 32.0% (95/297), and
      0, and those among the patients with moderate inhalation injury were respectively
      0,53.7% (58/108), and 46.3% (50/108). There were statistically significant
      differences in degree of burn of larynx of patients with different degree of
      inhalation injury (chi2 = 336.703, P < 0.001). Correlation analysis showed that
      severity of burn of larynx was positively correlated with severity of inhalation
      injury (r = 0.700, P < 0.001). (2) The rate of tracheotomy was 37.02% (164/443).
      The rates of tracheotomy in patients with mild, moderate, and severe inhalation
      injury were respectively 10.44% (31/297), 87.96% (95/108), and 100.00% (38/38),
      chi2 = 271.654, P < 0.001. Correlation analysis showed that the rate of
      tracheotomy was positively correlated with severity of inhalation injury (r =
      0.784, P < 0.001). Tracheotomy was done mainly within 6 h post burn (63.4%,
      104/164). The incidence rate of complication of tracheotomy was 5.5% (9/164). (3)
      Thirty-one patients died, with a mortality rate of 7.00%. The mortality rates of
      patients with mild, moderate, and severe inhalation injury were respectively
      1.01% (3/297), 12.96% (14/108), and 36.84% (14/38), H = 74.273, P < 0.001. It was
      found that the mortality was positively correlated with severity of inhalation
      injury (r = 0.371, P < 0.001). The causes of death of the patients were
      respectively sepsis (14, 45.2%), respiratory failure (7, 22.6%), airway
      obstruction (2, 6.5%), airway hemorrhage (2, 6.5%), cerebral hemorrhage (2,
      6.5%), cardiac accident (2, 6.5%), and diabetes insipidus (1, 3.2%), and 1 (3.2%)
      patient quit treatment and discharged from hospital for economic reason.
      CONCLUSIONS: Among the patients with inhalation injury, male is dominated in
      number, and the young adults formed the highest constituent ratio. The severity
      of inhalation injury was correlated with total burn area, severity of burn of
      larynx, tracheotomy rate, and mortality. With the guidance of diagnostic criteria
      of burn of larynx and indication of tracheotomy, the risk of laryngeal
      obstruction can be eliminated. The early preventive tracheotomy can decrease the
      difficulty and risk of the operation.

PMID- 25572890
TI  - [Repair of deep wound on thumb using island flap from dorsoulnar side of thumb].
AB  - OBJECTIVE: To study the effect of island flap from dorsoulnar side of thumb in
      repairing deep wound on thumb. METHODS: Twenty-two patients with deep wound on
      thumb were hospitalized from May 2007 to December 2013. The wounds ranged from
      2.0 cm x 1.5 cm to 4.0 cm x 2.5 cm in area. Island flap of dorsoulnar thumb was
      used to repair these defects, with flap area ranging from 2.1 cm x 1.6 cm to 4.1
      cm x 2.6 cm. All the donor sites were closed by transplantation of full-thickness
      skin from upper medial arm. RESULTS: All flaps survived with good blood supply.
      All deep wounds of thumb were closed. Skin grafts of donor sites all survived.
      Patients were followed up for 6 to 12 months. The texture, color, and shape of
      all flaps were satisfactory, and functions of injured thumbs recovered well.
      CONCLUSIONS: Transplantation of island flap from dorsoulnar side of thumb can be
      performed easily with high survival rate and satisfactory configuration, and it
      is suitable for repairing deep wound of thumb.

PMID- 25572891
TI  - [Causation, prevention and treatment of dust explosion].
AB  - With the development of industrial technology, dust explosion accidents have
      increased, causing serious losses of people's lives and property. With the
      development of economy, we should lay further emphasis on causation, prevention,
      and treatment of dust explosion. This article summarizes the background,
      mechanism, prevention, and treatment of dust explosion, which may provide some
      professional knowledge and reference for the treatment of dust explosion.

PMID- 25572892
TI  - [Repair of skin and soft tissue defects on the wrist with reverse bi-pedicle
      posterior interosseous artery perforator flap].
AB  - OBJECTIVE: To explore the curative effect of reverse bi-pedicle posterior
      interosseous artery perforator flap in repairing skin and soft tissue defects on
      the wrist. METHODS: Seven patients with soft tissue defects on the wrist,
      including simple skin and soft tissue defects in 4 cases and skin and soft tissue
      defects combined with radial tendon injury in 3 cases, were hospitalized from
      December 2010 to March 2012. The area of skin defect on the volar side of the
      wrist ranged from 4.8 cm x 4.0 cm to 6.2 cm x 4.5 cm, while that on the dorsal
      side ranged from 3.5 cm x 3.2 cm to 6. 5 cm x 5.4 cm. These wounds were
      respectively caused by traffic injury (3 cases), reamer injury (2 cases), burn (1
      case), and tumor resection (1 case). Reverse bi-pedicle posterior interosseous
      artery perforator flaps were used to repair these defects, with area of one
      pedicle ranging from 2.5 cm x 2.0 cm to 3.5 cm x 2.5 cm and the area of the other
      pedicle ranging from 2.5 cm x 2.5 cm to 4.0 cm x 3.0 cm. The donor sites were
      closed by suturing. RESULTS: All flaps survived completely. Patients were
      followed up for 6 to 36 months. The color, texture, and appearance of all flaps
      were satisfactory. At last follow-up, distances of two-point discrimination of
      flaps ranged from 9 to 13 mm. The dorsal extension and palmar flexion functions
      of wrist were satisfactory. The results of function evaluation of 7 wrists were
      excellent in 6 cases and good in 1 case according to the tentative standards for
      the evaluation of upper extremity function of Society of Hand Surgery of Chinese
      Medical Association. A linear scar was formed at the donor site. CONCLUSIONS: The
      reverse bi-pedicle posterior interosseous artery perforator flap, with advantages
      of flexible design, easy to achieve, less injury to donor site, and reliable
      blood supply, etc., is another choice for repairing skin and soft tissue defects
      over the wrist.

PMID- 25572893
TI  - [Genotyping and drug resistance of methicillin-resistant Staphylococcus aureus].
AB  - OBJECTIVE: To investigate the genotype of staphylococcal chromosomal cassette mec
      (SCCmec) in methicillin-resistant Staphylococcus aureus (MRSA) isolated from burn
      wards and its current status of drug resistance. METHODS: One hundred and seventy
      nine strains of Staphylococcus aureus were isolated from wound excretion, blood,
      and sputum samples of patients that were admitted to ICU or public wards of our
      Department of Burns and Plastic Surgery from September 2012 to September 2013.
      Among them, 68 strains were from ICU and 111 strains from public wards. The MRSA
      phenotype of Staphylococcus aureus was detected with cefoxitin K-B disk diffusion
      method, and the isolation rates of MRSA in ICU and public wards were compared.
      Genotyping of SCCmec was performed by PCR in strains of MRSA. In the meantime,
      the identification result of MRSA by K-B method was verified through detecting
      methicillin-resistant determinant mecA. The antimicrobial resistance of MRSA and
      methicillin-sensitive Staphylococcus aureus (MSSA) to 23 kinds of commonly used
      antibiotics in clinic were detected by K-B disk diffusion method. Except for the
      antibiotics to which the resistant rates of MRSA were 100.0% or 0, the resistant
      rates of SCCmecIII MRSA and non-SCCmec III MRSA to the rest of antibiotics were
      compared. Data were processed with Pearson chi-square test or corrected chi
      square test. RESULTS: One hundred and forty-eight strains out of the 179
      Staphylococcus aureus were identified as MRSA (accounting for 82.7%), among which
      62 were originated from ICU and 86 from public wards. The rest 31 strains of
      Staphylococcus aureus were MSSA, accounting for 17.3%. The percentage of MRSA in
      the isolated Staphylococcus aureus was 91.2% (62/68) in ICU, which was
      significantly higher than that in the public wards [77.5% (86/111), chi2 = 5.526,
      P = 0.019]. PCR detection showed that the 148 strains of MRSA harbored the mecA
      gene, out of which 106 strains were SCCmec III positive, accounting for 71.6%.
      The percentages of SCCmec III type MRSA in MRSA isolated from ICU and public
      wards were respectively 72.6% (45/62) and 70.9% (61/86), showing no statistically
      significant difference (chi2 = 0.048, P = 0.826). The 148 strains of MRSA were
      100.0% resistant to a total of 8 kinds of antibiotics including penicillin and
      cephalosporins, but it was 0 for vancomycin, teicoplanin, linezolid, tigecycline,
      nitrofurantoin, and quinupristin/dalfopristin. Except for the 6 kinds of
      antibiotics to which the resistant rates of MRSA and MSSA were 0, resistant rates
      of MRSA to the remaining 17 kinds of antibiotics were significantly higher than
      those of MSSA (with chi2 values from 4.091 to 138.546, P < 0.05 or P < 0.01).
      Resistant rates of the 106 strains of SCCmecIII type MRSA to levofloxacin,
      ciprofloxacin, rifampicin, tetracycline, erythrocin, lincomycin, gentamicin,
      clindamycin were respectively 56.6% (60/106), 85.8% (91/106), 89.6% (95/106),
      86.8% (92/106), 84.9% (90/106), 78.3% (83/106), 92.5% (98/106), 74.5% (79/106),
      and they were significantly higher than those of the 42 strains of non-SCCmec III
      type MRSA [33.3% (14/42), 61.9% (26/42), 71.4% (30/42), 66.7% (28/42), 69.0%
      (29/42), 57.1% (24/42), 71.4% (30/42), 52.4% (22/42), with chi2 values from 4.801
      to 11.377, P < 0.05 or P < 0.01]. CONCLUSIONS: Isolation rate of MRSA from burn
      wards in our hospital is high, and drug resistance status of this strain against
      antibiotics is very serious. SCCmec III is the major genotype of the isolated
      MRSA, but no strains resistant to the glycopeptide antibiotics are found.

PMID- 25572894
TI  - [Advances in the research of promoting healing of chronic wound with platelet
      rich plasma].
AB  - Normal wound healing is a well-orchestrated process of inflammatory response,
      cell proliferation, and tissue remodeling. However, this orderly and precise
      process is impaired in chronic wounds. A series of complicated pathogenic
      factors, including enhanced inflammatory response, poor cell proliferation,
      restrained angiogenesis, restricted collagen deposition, and infection,
      contribute to the failure of healing of chronic wound. The application of
      platelet-rich plasma (PRP) has been explored as a treatment for chronic wounds as
      it can balance wound microenvironment for promoting wound healing. PRP can
      modulate the inflammatory mediators, growth factors, and cytokines, etc. to
      correct abnormal biological events and disorderly molecular environment of cell
      migration and proliferation, and thus promote wound healing appropriately. Yet,
      the mechanism of PRP in promoting healing of chronic wound is still not
      elaborated, and the clinical application of PRP needs to be standardized as soon
      as possible.

PMID- 25572895
TI  - [Advances in the research and application of prefabricated flap].
AB  - Prefabricated flap is so named as the skin flaps is prepared by prefabricating a
      circulation-rich skin flap by implanting a named blood vessel or a portion of
      fascia which is incorporated with rich blood supply. After the flap has been
      proven as a flap supplied by ample blood supply, it is transplanted to a wound as
      a local or free transplantation. The core of prefabricated flap is
      vascularization. Beside the different methods of prefabrication, vascularization
      can be facilitated by use of growth factors and cytokines, skin and soft tissue
      expansion technique, and biomaterial. Prefabricated flap is currently widely used
      in clinic. With the advances in the research of prefabrication technology and
      advances in its clinical application, prefabricated flap transplantation is
      becoming a promising strategy in wound healing.

PMID- 25572896
TI  - Epidemiological, clinical, outcome and antibiotic susceptibility differences
      between PVL positive and PVL negative Staphylococcus aureus infections in Western
      Australia: a case control study.
AB  - BACKGROUND: Panton Valentine Leukocidin (PVL) has been associated with invasive
      Staphylococcus aureus soft tissue and pneumonic infections. METHODS: From
      September 2007 to January 2009 at Royal Perth Hospital we tested for the PVL gene
      in S. aureus isolates from an invasive site, a suspected PVL-related soft tissue
      infection and all MRSA isolates. We could access medical records for 141 PVL
      positive (PVL + ve) infections and compared these to a control group comprised of
      148 PVL negative (PVL-ve) infections. RESULTS: In the PVL + ve group 62 isolates
      were MRSA (48 were ST93-MRSA-IV) and 79 isolates were methicillin-sensitive S.
      aureus, and in the PVL-ve group 56 were MRSA (50 were WA-MRSA strains) and 92
      were methicillin-sensitive S. aureus. We found the presence of PVL to be
      significantly associated with younger age, aboriginality, intravenous drug use,
      community acquisition, shorter length of hospital stay and lower mortality at 1
      year. Overall PVL + ve infections more often required surgical intervention
      (73.0% versus 44.6%, p < 0.001) and were less often polymicrobial (8.5% versus
      41.2%, p < 0.001). PVL + ve isolates were more often susceptible to clindamycin
      (87.9% versus 73.0%, p = 0.002). CONCLUSIONS: This study demonstrates that PVL +
      ve infections are associated with a distinct clinical picture, predominantly
      pyogenic skin and soft tissue infections often requiring surgery,
      disproportionately affecting patients who are younger, indigenous or with fewer
      health-care risk factors.

PMID- 25572897
TI  - The influence of mood on the process and content of encoding future intentions.
AB  - Remembering to perform an intention in the future when some environmental cue is
      encountered is referred to as event-based prospective memory. The influence of
      mood on this future-oriented memory is unclear. By experimentally manipulating
      mood, the current set of experiments sought to examine the influence that
      differing mood states have on encoding future intentions. Participants were
      induced into a neutral, positive, or negative mood state at intention formation
      and returned to their baseline mood before beginning the prospective memory task.
      Relative to the neutral mood, positive mood facilitated and negative mood
      impaired intention encoding when neutrally toned cues were used, as evidenced by
      the proportion of cues subsequently detected. The use of negatively toned cues
      ameliorated the benefit of the positive mood but not the impairment of the
      negative mood. Further, reinstatement of the encoding mood during retrieval
      equated performance for all three mood conditions. Results suggest that encoded
      mood influences the future accessibility and completion of intended behaviours,
      perhaps through modulation of associative processing. The current study
      demonstrates that mood plays a determining role in encoding future intentions. 

PMID- 25572900
TI  - Editorial commentary: Unbiased next-generation sequencing and new pathogen
      discovery: undeniable advantages and still-existing drawbacks.

PMID- 25572899
TI  - Astrovirus VA1/HMO-C: an increasingly recognized neurotropic pathogen in
      immunocompromised patients.
AB  - BACKGROUND: An 18-month-old boy developed encephalopathy, for which extensive
      investigation failed to identify an etiology, 6 weeks after stem cell transplant.
      To exclude a potential infectious cause, we performed high-throughput RNA
      sequencing on brain biopsy. METHODS: RNA-Seq was performed on an Illumina Miseq,
      generating 20 million paired-end reads. Nonhost data were checked for similarity
      to known organisms using BLASTx. The full viral genome was sequenced by primer
      walking. RESULTS: We identified an astrovirus, HAstV-VA1/HMO-C-UK1(a), which was
      highly divergent from human astrovirus (HAstV 1-8) genotypes, but closely related
      to VA1/HMO-C astroviruses, including one recovered from a case of fatal
      encephalitis in an immunosuppressed child. The virus was detected in stool and
      serum, with highest levels in brain and cerebrospinal fluid (CSF).
      Immunohistochemistry of the brain biopsy showed positive neuronal staining. A
      survey of 680 stool and 349 CSF samples identified a related virus in the stool
      of another immunosuppressed child. CONCLUSIONS: The discovery of HAstV-VA1/HMO-C
      UK1(a) as the cause of encephalitis in this case provides further evidence that
      VA1/HMO-C viruses, unlike HAstV 1-8, are neuropathic, particularly in
      immunocompromised patients, and should be considered in the differential
      diagnosis of encephalopathy. With a turnaround from sample receipt to result of
      <1 week, we confirm that RNA-Seq presents a valuable diagnostic tool in
      unexplained encephalitis.

PMID- 25572901
TI  - Dimensions of Poverty and Health Outcomes Among People Living with HIV Infection:
      Limited Resources and Competing Needs.
AB  - HIV infection is concentrated in populations living in poverty. We examined the
      overlapping and independent effects of multiple poverty indicators on HIV-related
      health status. Because substance use can create competing survival needs when
      resources are limited, we also sought to objectively measure expenditures on food
      relative to alcohol and tobacco products. To achieve these aims, 459 men and 212
      women living with HIV infection in Atlanta, GA completed measures of socio
      demographic and heath characteristics as well as multiple indicators of poverty
      including housing stability, transportation, food insecurity, and substance use.
      Participants were given a $30 grocery gift card for their participation and we
      collected receipts which were coded for alcohol (beer, wine, liquors) and tobacco
      purchases. Results showed that participants with unsuppressed HIV replication
      were significantly more likely to experience multiple indicators of poverty. In
      addition, one in four participants purchased alcohol or tobacco products with
      their gift cards, with as much as one-fourth of money spent on these products. A
      multivariable logistic regression model showed that food insecurity was
      independently associated with unsuppressed HIV, and purchasing alcohol or tobacco
      products did not moderate this association. Results confirm previous research to
      show the primacy of food insecurity in relation to HIV-related health outcomes.
      Competing survival needs, including addictive substances, should be addressed in
      programs that aim to alleviate poverty to enhance the health and well-being of
      people with HIV infection. 

PMID- 25572898
TI  - Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult
      with encephalitis by unbiased next-generation sequencing.
AB  - Metagenomic next-generation sequencing (NGS) was used to diagnose an unusual and
      fatal case of progressive encephalitis in an immunocompromised adult presenting
      at disease onset as bilateral hearing loss. The sequencing and confirmatory
      studies revealed neuroinvasive infection of the brain by an astrovirus belonging
      to a recently discovered VA/HMO clade. 

PMID- 25572903
TI  - Response styles, bipolar risk, and mood in students: The Behaviours Checklist.
AB  - OBJECTIVES: An Integrative Cognitive Model of mood swings and bipolar disorder
      proposes that extreme positive and negative appraisals about internal states
      trigger ascent and descent behaviours, contributing to the onset and maintenance
      of mood swings. This study investigated the reliability and validity of a new
      inventory, the Behaviours Checklist (BC), by measuring associations with
      appraisals, response styles to positive and negative affect, bipolar risk, mania,
      and depression. DESIGN: Correlational analogue study. METHODS: Students (N = 134)
      completed the BC alongside measures of appraisals, response styles to positive
      and negative mood, mania, depression, and hypomanic personality (bipolar risk).
      RESULTS: The BC was of adequate reliability and showed good validity. Ascent
      behaviours and appraisals predicted bipolar risk, whereas descent behaviours and
      appraisals were associated with depression. CONCLUSIONS: Appraisals, ascent, and
      descent behaviours may play an important role in the development and maintenance
      of mood swings. Limitations and research recommendations are outlined.
      PRACTITIONER POINTS: Extreme positive and negative appraisals of internal states,
      and subsequent behavioural responses (ascent and descent behaviours), are
      associated with bipolar risk and bipolar mood symptoms in a student sample. These
      processes are involved with mood dysregulation in clinical populations as well as
      bipolar risk in students, with implications for mood management.

PMID- 25572904
TI  - Research unit of the Spanish Academy of Dermatology and Venerology Foundation.

PMID- 25572905
TI  - Cutaneous metastasis from hepatocellular carcinoma after a percutaneous
      interventional procedure.

PMID- 25572906
TI  - Fine-needle aspiration cytology of the solid variant of papillary thyroid
      carcinoma: a study of 13 cases with clinical, histologic, and ultrasound
      correlations.
AB  - BACKGROUND: The solid variant of papillary thyroid carcinoma (SVPTC) comprises
      approximately 3% of thyroid cancers, and there are conflicting reports about its
      behavior in the literature. The cytology of SVPTC is limited to 3 single case
      reports, a review article, and a monograph. We present the first cytologic study
      of SVPTC. METHODS: Fine-needle aspiration smears obtained with ultrasound
      guidance from 13 patients with histologically pure SVPTC were reviewed, and the
      cytologic features recorded. Ultrasound images were retrieved from radiology and
      were correlated with low-power histology images. Intratumor vascularity on
      Doppler imaging was correlated with cellularity in cytology samples. RESULTS:
      Three cytomorphologic patterns of SVPTC were identified: cohesive, syncytial-type
      tissue fragments; microfollicles/trabeculae; and dyshesive single cells. All 3
      SVPTCs in the first group were encapsulated without invasion. Two of 6 SVPTCs in
      the second group had a single lymph node metastasis; 4 were encapsulated, and 2
      had pushing borders. Ultrasound images in the first and second SVPTC groups were
      similar, with the majority revealing a well defined, solid nodule with minimal
      intranodular vascularity. All 4 SVPTCs in the third group had infiltrative
      borders; and, with the exception of one 0.8-cm tumor, all had multiple lymph node
      metastases. Ultrasound in the third group revealed irregular borders. RET/PTC1
      and RET/PTC3 mutations were found in 2 cases of the third group. CONCLUSIONS:
      SVPTCs are heterogeneous tumors. The cohesive, syncytial tissue-fragment pattern
      can be recognized as SVPTC in smears and is associated with encapsulation and
      indolent behavior. The microfollicular/trabecular pattern is indistinguishable
      from that of the follicular variant of papillary thyroid carcinoma and has
      intermediate behavior. The dyshesive single-cell pattern correlates with
      infiltrative tumor growth and may not be unique to SVPTC.

PMID- 25572907
TI  - Origins of the breast milk-derived cells; an endeavor to find the cell sources.
AB  - Fresh human breast milk consists of a heterogeneous population of cells that may
      offer a non-invasive source of cells for therapeutic proposes. The aims of this
      study were to characterize the breast milk-derived cells cultured in vitro. To do
      this, the cells from human breast milk were cultured and the expression of the CD
      markers along with the embryonic stem cell markers, endothelial and luminal
      mammary epithelial cell markers was evaluated by flow cytometry and
      immunofluorescence. The presence of fetal microchimerism among the isolated cells
      was also determined by the presence of SRY gene. They were also differentiated
      into adipocytes and osteoblasts. The results showed that a remarkable number of
      cells expressed the mesenchymal stem cell (MSC) markers such as CD90, CD44,
      CD271, and CD146. A subpopulation of the human breast milk-derived cells (HBMDC)
      also expressed the embryonic stem cell markers, such as TRA 60-1, Oct4, Nanog and
      Sox2 but not SSEA1 or 4. The frequencies of the cells which expressed the
      endothelial, hematopoietic cell markers were negligible. SRY gene was not
      detected in the breast milk isolated cells. A subpopulation of the cells also
      expressed cytokeratin 18, the marker of luminal mammary epithelial cells. These
      cells showed the capability to differentiate into adipocytes and osteoblasts. In
      conclusion, these finding highlighted the presence of cells with various sources
      in the breast milk. Different stem cells including MSCs or embryonic stem cell
      like cell along with the exfoliated cells from luminal epithelial cells were
      found among the isolated cells. The breast milk-derived stem cells might be
      considered as a non-invasive source of the stem cells for therapeutic purpose. 

PMID- 25572909
TI  - A high performance O2 selective membrane based on CAU-1-NH2@polydopamine and the
      PMMA polymer for Li-air batteries.
AB  - A novel mixed matrix membrane (MMM) was prepared by incorporating polydopamine
      coated metal organic framework (MOF) crystals of CAU-1-NH2 into a PMMA
      (polymethylmethacrylate) matrix. The MMM possesses the advantages of high O2
      permeability, high capability of carbon dioxide capture, and excellent
      hydrophobic behavior. The MMM was assembled in the Li-air batteries which
      displayed promising electrochemical performance in the real ambient air with 30%
      relative humidity. 

PMID- 25572908
TI  - Standard pre- and postoperative determination of chromogranin a in resectable non
      functioning pancreatic neuroendocrine tumors--diagnostic accuracy: NF-pNET and
      low tumor burden.
AB  - BACKGROUND: Chromogranin A (CgA) is often used in metastatic patients with
      nonfunctioning pancreatic neuroendocrine tumors (NF-pNET). The aim of this study
      is to assess the diagnostic accuracy of CgA in patients with low tumor burden.
      METHODS: Resectable patients with NF-pNET without metastases at time of diagnosis
      were included between 2002 and 2013 in the Academic Medical Center of Amsterdam.
      CgA was determined at time of diagnosis and during follow-up according to a
      standardized method. The upper reference range was 94 ug/l. RESULTS: Overall, 47
      patients were included in this study. CgA was elevated preoperatively in only 10
      patients (27%). In the detection of metastases during follow-up, the positive
      predictive value for CgA was 50% and negative predictive value was 81%. In 50% of
      the patients with an elevated CgA during follow-up, this test result was false
      positive. CONCLUSIONS: The diagnostic accuracy of CgA was low preoperatively in
      patients with resectable NF-pNET and low tumor burden. In the detection of
      recurrent disease after curative resection of NF-pNET, the diagnostic accuracy of
      CgA was moderate (50%). We conclude that the routine measurement of CgA at time
      of diagnosis or during follow-up after curative resection had limited value in
      patients with resectable NF-pNET.

PMID- 25572910
TI  - Fatal paroxysmal non-kinesigenic dyskinesia.

PMID- 25572912
TI  - Treatment efficacy differences of sorafenib for advanced hepatocellular
      carcinoma: a meta-analysis of randomized clinical trials.
AB  - OBJECTIVES: Hepatocellular carcinoma (HCC) is a heterogeneous disease. We
      explored whether any specific subgroups of patients may gain more survival
      benefits from sorafenib as the first-line therapy for advanced HCC. METHODS:
      PubMed and the Cochrane library were searched for phase III clinical trials that
      compared sorafenib with other treatments as first-line therapy for advanced HCC.
      We retrieved data from the published articles and then calculated synthesized
      hazard ratios (HRs) of overall mortality for patients of different subgroups,
      using patients who received other treatments as the reference. RESULTS: Four
      phase III clinical trials comparing sorafenib with other treatments were included
      in this study. The HRs were not significantly different between patients from
      various geographic regions (p = 0.183), patients with different Eastern
      Cooperative Oncology Group performance statuses (p = 0.699), or patients with
      different tumor involvement (p = 0.221). By contrast, the synthesized HR for
      hepatitis C virus (HCV)+ patients was 0.65 [95% confidence interval (CI) 0.53
      0.80], which was significantly lower than that for HCV- patients (0.87, 95% CI
      0.79-0.96, p = 0.013). CONCLUSIONS: As the first-line therapy for advanced HCC,
      sorafenib might provide more survival benefits to HCV+ patients than to HCV-
      patients.

PMID- 25572913
TI  - Second primary head and neck cancer after Hodgkin lymphoma: a population-based
      study of 44,879 survivors of Hodgkin lymphoma.
AB  - BACKGROUND: Survivors of Hodgkin lymphoma (HL) are at an increased risk of
      developing second malignancies. To the authors' knowledge, the risks of head and
      neck cancer (HNC) after HL and subsequent survival have not been thoroughly
      investigated. METHODS: From the US population-based Surveillance, Epidemiology,
      and End Results (SEER) database for 1973 through 2011, survivors of HL who
      developed HNC as a second cancer were analyzed. Patients with a first primary HNC
      were used as a comparison group. Observed-to-expected ratios and summary
      statistics were performed on patients with HL with squamous cell carcinoma (HL
      SCC) and salivary gland cancer (HL-SGC). The impact of HL history on overall
      survival was assessed using a multivariate Cox proportional hazards model.
      RESULTS: The observed-to-expected ratio for SCC among patients with HL was 1.73
      (95% confidence interval [95% CI], 1.36-2.16; P<.05), whereas it was 8.56 for SGC
      (95% CI, 5.82-12.15; P<.05). Using Cox proportional hazards modeling, a history
      of HL was found to be an adverse prognostic factor for overall survival for SCC
      (hazard ratio, 1.37; 95% CI, 1.08-1.73 [P = .009]) but not SGC (hazard ratio,
      1.21; 95% CI, 0.82-1.79 [P = .34]). The inferior survival of the patients in the
      HL-SCC cohort appears to be attributable to more deaths from HL and other
      malignancies diagnosed after SCC. CONCLUSIONS: There is a significantly increased
      risk of salivary and nonsalivary HNC after HL, and worse survival for patients
      with HL-SCC versus those with a first primary SCC. Clinicians should be aware of
      the risks of HNC after HL. In the absence of evidence-based criteria, the authors
      recommend that survivors of HL undergo periodic head and neck examination.

PMID- 25572914
TI  - Robustness of birth-death and gain models for inferring evolutionary events.
AB  - BACKGROUND: Phylogenetic birth-death models are opening a new window on the
      processes of genome evolution in studies of the evolution of gene and protein
      families, protein-protein interaction networks, microRNAs, and copy number
      variation. Given a species tree and a set of genomic characters in present-day
      species, the birth-death approach estimates the most likely rates required to
      explain the observed data and returns the expected ancestral character states and
      the history of character state changes. Achieving a balance between model
      complexity and generalizability is a fundamental challenge in the application of
      birth-death models. While more parameters promise greater accuracy and more
      biologically realistic models, increasing model complexity can lead to
      overfitting and a heavy computational cost. RESULTS: Here we present a
      systematic, empirical investigation of these tradeoffs, using protein domain
      families in six metazoan genomes as a case study. We compared models of
      increasing complexity, implemented in the Count program, with respect to model
      fit, robustness, and stability. In addition, we used a bootstrapping procedure to
      assess estimator variability. The results show that the most complex model, which
      allows for both branch-specific and family-specific rate variation, achieves the
      best fit, without overfitting. Variance remains low with increasing complexity,
      except for family-specific loss rates. This variance is reduced when the number
      of discrete rate categories is increased. CONCLUSIONS: The work presented here
      evaluates model choice for genomic birth-death models in a systematic way and
      presents the first use of bootstrapping to assess estimator variance in birth
      death models. We find that a model incorporating both lineage and family rate
      variation yields more accurate estimators without sacrificing generality. Our
      results indicate that model choice can lead to fundamentally different
      evolutionary conclusions, emphasizing the importance of more biologically
      realistic and complex models.

PMID- 25572915
TI  - Negative life events and symptoms of depression and anxiety: stress causation
      and/or stress generation.
AB  - BACKGROUND AND OBJECTIVES: Stressful life events are known to contribute to
      development of depression; however, it is possible this link is bidirectional.
      The present study examined whether such stress generation effects are greater
      than the effects of stressful life events on depression, and whether stress
      generation is also evident with anxiety. DESIGN: Participants were two large age
      cohorts (N = 732 aged 44 years; N = 705 aged 63 years) from the West of Scotland
      Twenty-07 study. METHODS: Stressful life events, depression, and anxiety symptoms
      were measured twice five years apart. Cross-lagged panel analysis examined the
      mutual influences of stressful life events on depression and on anxiety over
      time. RESULTS: Life events predicted later depressive symptomatology (p = .01),
      but the depression predicting life events relationship was less strong (p = .06),
      whereas earlier anxiety predicted life events five years later (p = .001). There
      was evidence of sex differences in the extent to which life events predicted
      later anxiety. CONCLUSIONS: This study provides evidence of stress causation for
      depression and weaker evidence for stress generation. In contrast, there was
      strong evidence of stress generation for anxiety but weaker evidence for stress
      causation, and that differed for men and women.

PMID- 25572916
TI  - Transdermal Methyl Alcohol Intoxication: A Case Report.

PMID- 25572917
TI  - A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly
      diagnosed multiple myeloma not eligible for or who deferred autologous stem cell
      transplantation.
AB  - Once-weekly administration of bortezomib has reduced bortezomib-induced
      peripheral neuropathy without affecting response rates, but this has only been
      demonstrated prospectively in three- and four- drug combinations. We report a
      phase II trial of alternate dosing and schedule of bortezomib and dexamethasone
      in newly diagnosed multiple myeloma patients who are not eligible for or refused
      autologous stem cell transplantation. Bortezomib 1.6 mg/m(2) intravenously was
      given once-weekly for six cycles, together with dexamethasone 40 mg on the day of
      and day after bortezomib. Fifty patients were enrolled; 58% did not require any
      dose modification. The majority of patients had multiple co-morbidities,
      including cardiovascular (76%) and renal insufficiency (54%), and the median
      number of medications prior to enrollment was 13. Of all evaluable patients, the
      overall response rate was 79% and at least 45% had at least a very good partial
      response. The median time to first response was 1.3 months (range, 0.25-2.4
      months). The progression-free and overall survivals were 8 months and 46.5
      months, respectively. Twenty-four percent developed worsening neuropathy. We
      conclude that alternate dosing and scheduling of bortezomib and dexamethasone is
      both safe and effective for management of newly diagnosed multiple myeloma in
      frail patients. (ClinicalTrials.gov number, NCT01090921). 

PMID- 25572918
TI  - Valproate attenuates the proteinuria, podocyte and renal injury by facilitating
      autophagy and inactivation of NF-kappaB/iNOS signaling in diabetic rat.
AB  - Epigenetic modifications are increasingly recognized to play a significant
      contribution in diabetic nephropathy (DN). Histone deacetylases (HDACs) are the
      emerging target in the pathogenesis and progression of DN. Valproic acid (VPA), a
      widely used anti-epileptic drug and has been proven as an HDAC inhibitor. This
      study was aimed to evaluate the protective roles of VPA on HDAC-mediated NF
      kappaB/iNOS signaling and autophagy in DN. Diabetes was induced by a single
      injection of STZ (50 mg/kg), whereas VPA at the doses of 150 and 300 mg/kg/day
      for 8 weeks was administered by oral route in Sprague-Dawley rat. Blood and urine
      were collected before animal were sacrificed, while kidneys were dissected after
      sacrificed. The podocyte and renal injuries were assessed using biochemical
      markers, histology, podocyte effacement, DNA damage and apoptosis as well as
      protein expression evaluation. VPA treatment improves the plasma and urinary
      biomarkers of renal function, decreased expression of iNOS, 3-nitrotyrosine, NF
      kappaB, p-NF-kappaB, HDAC4/5, calmodulin, calbindin, apoptosis and DNA damage.
      Further, VPA treatment increased histone acetylation and ameliorated the
      histological alterations and podocyte effacement. Interestingly, VPA treatment
      also restored diabetes-associated perturbations in autophagy by HDAC inhibition.
      To the best of our knowledge, this is the first report, which highlights the
      beneficial role of VPA in DN. The present results clearly exhibited that VPA
      treatment ameliorates the podocyte and renal injuries mainly by facilitating the
      autophagy and inactivation of NF-kappaB/iNOS signaling. The present findings
      demonstrated that VPA may be useful in the treatment of DN, since the present
      experimental doses are clinically relevant. 

PMID- 25572919
TI  - ATDOF5.8 protein is the upstream regulator of ANAC069 and is responsive to
      abiotic stress.
AB  - ANAC069 encodes a plasma membrane-bound NAC protein that integrates auxin and
      salt signals to regulate Arabidopsis thaliana seed germination. However, the
      regulatory network of ANAC069 has not been revealed. Here, we report that ANAC069
      is a direct target gene of the ATDOF5.8 transcription factor. There are seven DOF
      motifs in the promoter of ANAC069, which is highly enriched in the promoter.
      Yeast one-hybrid (Y1H) assays showed that a Dof protein, ATDOF5.8, binds to the
      DOF motifs. The interaction between ATDOF5.8 and the promoter of ANAC069 was
      further confirmed by transient expression assays in tobacco leaves. Chromatin
      Immunoprecipitation (ChIP) results suggested that the binding of ATDOF5.8 to DOF
      motifs in the promoter of ANAC069 occurs in vivo in Arabidopsis to regulate the
      expression of ANAC069. Moreover, ATDOF5.8 and ANAC069 share similar expression
      patterns in response to salt, drought and ABA treatment. Taken together, the
      results suggested a regulatory network model mediated by ANAC069, under abiotic
      stress conditions, ATDOF5.8 regulates the expression of ANAC069, and the
      activated ANAC069 binds to NAC recognition sequences or other motifs to regulate
      the expression of genes containing these motifs in their promoters. 

PMID- 25572920
TI  - In vivo biofilm formation on stainless steel bonded retainers during different
      oral health-care regimens.
AB  - Retention wires permanently bonded to the anterior teeth are used after
      orthodontic treatment to prevent the teeth from relapsing to pre-treatment
      positions. A disadvantage of bonded retainers is biofilm accumulation on the
      wires, which produces a higher incidence of gingival recession, increased pocket
      depth and bleeding on probing. This study compares in vivo biofilm formation on
      single-strand and multi-strand retention wires with different oral health-care
      regimens. Two-centimetre wires were placed in brackets that were bonded to the
      buccal side of the first molars and second premolars in the upper arches of 22
      volunteers. Volunteers used a selected toothpaste with or without the additional
      use of a mouthrinse containing essential oils. Brushing was performed manually.
      Regimens were maintained for 1 week, after which the wires were removed and the
      oral biofilm was collected to quantify the number of organisms and their
      viability, determine the microbial composition and visualize the bacteria by
      electron microscopy. A 6-week washout period was employed between regimens.
      Biofilm formation was reduced on single-strand wires compared with multi-strand
      wires; bacteria were observed to adhere between the strands. The use of
      antibacterial toothpastes marginally reduced the amount of biofilm on both wire
      types, but significantly reduced the viability of the biofilm organisms.
      Additional use of the mouthrinse did not result in significant changes in biofilm
      amount or viability. However, major shifts in biofilm composition were induced by
      combining a stannous fluoride- or triclosan-containing toothpaste with the
      mouthrinse. These shifts can be tentatively attributed to small changes in
      bacterial cell surface hydrophobicity after the adsorption of the toothpaste
      components, which stimulate bacterial adhesion to the hydrophobic oil, as
      illustrated for a Streptococcus mutans strain. 

PMID- 25572922
TI  - Modern inhalational anesthetics for refractory status epilepticus.
AB  - BACKGROUND: Our goal was to perform a systematic review of the literature on the
      use of modern inhalational anesthetic agents for refractory status epilepticus
      and their impact on seizure control. METHODS: All articles from MEDLINE, BIOSIS,
      EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International
      Clinical Trials Registry Platform (inception to March 2014), reference lists of
      relevant articles, and gray literature were searched. The strength of evidence
      was adjudicated using both the Oxford and Grading of Recommendation Assessment
      Development and Education methodology by two independent reviewers. RESULTS:
      Overall, 19 studies were identified, with 16 manuscripts and 3 meeting abstracts.
      A total of 46 patients were treated. Adult (n=28) and pediatric patients (n=18)
      displayed 92.9% and 94.4% seizure control with treatment, respectively.
      Isoflurane was used in the majority of cases. Hypotension was the only
      complication described. CONCLUSIONS: Oxford level 4, Grading of Recommendation
      Assessment Development and Education D evidence exists to support the use of
      isoflurane in refractory status epilepticus to obtain burst suppression.
      Insufficient data exist to comment on the efficacy of desflurane and xenon at
      this time.

PMID- 25572923
TI  - Adaptive remodeling of the biliary architecture underlies liver homeostasis.
AB  - Serving as the center for metabolism and detoxification, the liver is inherently
      susceptible to a wide variety of damage imposed by toxins or chemicals. Induction
      of cell populations with biliary epithelial phenotypes, which include progenitor
      like cells and are referred to as liver progenitor cells, is often observed in
      histopathological examination of various liver diseases in both human patients
      and animal models and has been implicated in regeneration. However, the tissue
      dynamics underlying this phenomenon remains largely unclear. We have developed a
      simple imaging technique to reveal the global and fine-scale architecture of the
      biliary tract spreading in the mouse liver. Using this novel method, we show that
      the emergence and expansion of liver progenitor cells actually reflect structural
      transformation of the intrahepatic biliary tree in mouse liver injury models. The
      biliary branches expanded their area gradually and contiguously along with the
      course of chronic injury. Relevant regulatory signals known to be involved in
      liver progenitor cell regulation, including fibroblast growth factor 7 and tumor
      necrosis factor-like weak inducer of apoptosis, can modulate the dynamics of the
      biliary epithelium in different ways. Importantly, the structural transformations
      of the biliary tree were diverse and corresponded well with the parenchymal
      injury patterns. That is, when chronic hepatocyte damage was induced in the
      pericentral area, the biliary branches exhibited an extended structure from the
      periportal area with apparent tropism toward the distant injured area.
      CONCLUSION: The hepatobiliary system possesses a unique and unprecedented
      structural flexibility and can remodel dynamically and adaptively in response to
      various injury conditions; this type of tissue plasticity should constitute an
      essential component to maintain liver homeostasis.

PMID- 25572921
TI  - Cytoprotective nanoparticles by conjugation of a polyhis tagged annexin V to a
      nanoparticle drug.
AB  - We synthesized a cytoprotective magnetic nanoparticle by reacting a maleimide
      functionalized Feraheme (FH) with a disulfide linked dimer of a polyhis tagged
      annexin V. Following reductive cleavage of disulfide, the resulting annexin
      nanoparticle (diameter = 28.0 +/- 2.0 nm by laser light scattering, 7.6
      annexin's/nanoparticle) was cytoprotective to cells subjected to plasma membrane
      disrupting chemotherapeutic or mechanical stresses, and significantly more
      protective than the starting annexin V. Annexin-nanoparticles provide an approach
      to the design of nanomaterials which antagonize the plasma membrane permeability
      characteristic of necrosis and which may have applications as cytoprotective
      agents. 

PMID- 25572924
TI  - Influence of proton coupling on symmetry-based homonuclear (19)F dipolar
      recoupling experiments.
AB  - We study the efficiency of two symmetry based homonuclear (19)F double-quantum
      recoupling sequences for moderate (R142(6)) and ultra-fast (R144(5)) MAS under
      the influence of strong (1)H-(1)H and (1)H-(19)F dipolar interactions and (1)H
      continuous wave decoupling. Simulations based on various spin systems derived
      from the organic solid 1,3,5-tris(2-fluoro-2-methylpropionylamino)benzene (F
      BTA), used as a model system, reveal that the strong-decoupling limit is not
      accessible even for moderate spinning speeds. Additionally, for the no-decoupling
      limit improved DQ efficiencies are predicted for both moderate and ultra-fast
      MAS. Strong perturbations of build-up curves can be avoided by additional
      stabilisation through supercycling. Additional (1)H cw decoupling during (19)F
      recoupling rapidly reduces the maximum DQ efficiency when deviating from the no
      decoupling limit. These effects were confirmed by experimental data on F-BTA. For
      moderate spinning the influence of (1)H-(1)H and (1)H-(19)F couplings is markedly
      stronger compared to ultra-fast MAS. For the latter case those influences reduce
      to a constant scaling if only short excitation times up to the first minimum are
      taken into account. Based on this analysis the experimental build-up curves of
      1,3,5-tris(2-fluoro-2-methylpropionylamino)benzene can be refined with
      homonuclear (19)F spin systems which allow to probe even subtle structural
      differences for the fluorine atoms of F-BTA. 

PMID- 25572925
TI  - Automated tissue segmentation in breast MRI: an emerging tool with clinical
      potential.

PMID- 25572927
TI  - When quality improvement fails: a case study.

PMID- 25572926
TI  - Automated breast segmentation of fat and water MR images using dynamic
      programming.
AB  - RATIONALE AND OBJECTIVES: To develop and test an algorithm that outlines the
      breast boundaries using information from fat and water magnetic resonance images.
      MATERIALS AND METHODS: Three algorithms were implemented and tested using
      registered fat and water magnetic resonance images. Two of the segmentation
      algorithms are simple extensions of the techniques used for contrast-enhanced
      images: one algorithm uses clustering and local gradient (CLG) analysis and the
      other algorithm uses a Hessian-based sheetness filter (HSF). The third
      segmentation algorithm uses k-means++ and dynamic programming (KDP) for finding
      the breast pixels. All three algorithms separate the left and right breasts using
      either a fixed region or a morphological method. The performance is quantified
      using a mutual overlap (Dice) metric and a pectoral muscle boundary error. The
      algorithms are evaluated against three manual tracers using 266 breast images
      from 14 female subjects. RESULTS: The KDP algorithm has a mean overlap percentage
      improvement that is statistically significant relative to the HSF and CLG
      algorithms. When using a fixed region to remove the tissue between breasts with
      tracer 1 as a reference, the KDP algorithm has a mean overlap of 0.922 compared
      to 0.864 (P < .01) for HSF and 0.843 (P < .01) for CLG. The performance of KDP is
      very similar to tracers 2 (0.926 overlap) and 3 (0.929 overlap). The performance
      analysis in terms of pectoral muscle boundary error showed that the fraction of
      the muscle boundary within three pixels of reference tracer 1 is 0.87 using KDP
      compared to 0.578 for HSF and 0.617 for CLG. Our results show that the
      performance of the KDP algorithm is independent of breast density. CONCLUSIONS:
      We developed a new automated segmentation algorithm (KDP) to isolate breast
      tissue from magnetic resonance fat and water images. KDP outperforms the other
      techniques that focus on local analysis (CLG and HSF) and yields a performance
      similar to human tracers.

PMID- 25572928
TI  - The service encounter in radiology: acing the "moments of truth" to achieve
      patient-centered care.
AB  - Radiologists are increasingly recognizing their role as direct service providers
      to patients and seeking to offer an exceptional patient experience as part of
      high-quality service delivery. Patients' perceptions of service delivery are
      derived from the chain of numerous individual real-time encounters that occur
      throughout their visit. These so-called "moments of truth" define the overall
      experience and form the lasting impression of the given practice in their mind.
      Providing excellent service can be difficult to achieve in practice given its
      intangible nature as well as the heterogeneity and unpredictability of the large
      number of patients, frontline staff, and environmental circumstances that define
      the patient experience. Thus, broad commitment and team effort among all members
      of a radiology practice are required. This article explores important areas to be
      considered by a radiology practice to ensure positive and meaningful patient
      experiences. Specific ways in which every member within the practice, including
      schedulers, receptionists, technologists, nurses, and radiologists, can
      contribute to achieving high-quality patient service are discussed. Examples of
      patient-oriented language that may be useful in particular scenarios in radiology
      practice are given. The role of the practice's physical facility, including all
      aspects of its aesthetics and amenities, as well as of Internet services, in
      shaping the patient experience is also described. Throughout this work, a
      proactive approach to promoting a service-oriented organizational culture is
      provided. By improving the patient experience, these strategies may serve to
      enhance patients' perceptions of radiology and radiologists. 

PMID- 25572929
TI  - Stress decay, imaging plane, and gas bubble need to be considered when using
      ultrasound strain elastography to monitor hepatic ablations.

PMID- 25572930
TI  - Reply to letter: stress decay, imaging plane, and gas bubble need to be
      considered when using ultrasound strain elastography to monitor hepatic
      ablations.

PMID- 25572932
TI  - Alveolar and serum concentrations of imipenem in two lung transplant recipients
      supported with extracorporeal membrane oxygenation.
AB  - Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in
      patients with respiratory failure who fail conventional treatment. Postoperative
      pneumonia is the most common infection after lung transplantation (40%). Imipenem
      is frequently used for empirical treatment of nosocomial pneumonia in the
      intensive care unit. Nevertheless, few data are available on the impact of ECMO
      on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no
      guidelines exist for antibiotic dosing during ECMO support. We report the cases
      of 2 patients supported with venovenous ECMO for refractory acute respiratory
      distress syndrome following single lung transplantation for pulmonary fibrosis,
      treated empirically with 1 g of imipenem intravenously every 6 h. Enterobacter
      cloacae was isolated from the respiratory sample of Patient 1 and Klebsiella
      pneumoniae was isolated from the respiratory sample of Patient 2. Minimum
      inhibitory concentrations of the 2 isolated strains were 0.125 and 0.25 mg/L,
      respectively. Both patients were still alive on day 28. This is the first report,
      to our knowledge, of imipenem concentrations in lung transplantation patients
      supported with ECMO. This study confirms high variability in imipenem trough
      concentrations in patients on ECMO and with preserved renal function. An elevated
      dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and
      therapeutic drug monitoring is recommended, where available. Population
      pharmacokinetic studies are indicated to develop evidence-based dosing guidelines
      for ECMO patients. 

PMID- 25572933
TI  - Ethnobotanical study of medicinal plants in the environs of Tara-gedam and Amba
      remnant forests of Libo Kemkem District, northwest Ethiopia.
AB  - BACKGROUND: Remnant forests found in areas that have long been converted to
      agricultural landscapes are refuges of wild useful plants; and societies
      inhabiting them are custodians of rich indigenous botanical knowledge. This study
      was undertaken to document the medicinal plants used by the people living in and
      around Tara-gedam and Amba remnant forests, northwestern Ethiopia, together with
      the associated ethnomedicinal knowledge. METHODS: Data were collected from 105
      informants through semi-structured interviews, guided field walk, market survey;
      and analyzed using standard ethnobotanical analytical tools including ranking and
      comparison. RESULTS: A total of 163 medicinal plant species in 145 genera and 67
      families were recorded among which Zehneria scabra drew the highest community
      consensus. Seventy-one percent of the medicinal plants were those used for
      treating human ailments only, 21% for both human and livestock and 8% for
      livestock only. Asteraceae, with 14 species, had the highest number of medicinal
      plant species. The medicinal plants mainly (79.1%) belong to the shrub and herb
      categories and most of them were sourced from the wild habitats. Leaves and fresh
      plant materials were more frequently used for medicine preparation than other
      parts. Protected government and church forests as well as tree propagation in
      nurseries followed by planting them and local practices constitute the major
      forest conservation efforts that indirectly protect the medicinal plants in the
      area. Elders and healers knew more about the medicinal plants, their
      distribution, the local ethnomedicinal practices and knowledge transfer patterns.
      Though important for the local healthcare system and with potentials for modern
      drug discovery, both the plants and the knowledge pool are under threat.
      CONCLUSION: The diversity of medicinal plants and the associated indigenous
      knowledge of Tara-gedam and its environs are of a considerable value to the local
      community and beyond. There is, therefore, a need for conservation of the
      vegetation and the medicinal plants along with preservation of the wealth of the
      indigenous knowledge.

PMID- 25572931
TI  - The biopsychology of salt hunger and sodium deficiency.
AB  - Sodium is a necessary dietary macromineral that tended to be sparsely distributed
      in mankind's environment in the past. Evolutionary selection pressure shaped
      physiological mechanisms including hormonal systems and neural circuits that
      serve to promote sodium ingestion. Sodium deficiency triggers the activation of
      these hormonal systems and neural circuits to engage motivational processes that
      elicit a craving for salty substances and a state of reward when salty foods are
      consumed. Sodium deficiency also appears to be associated with aversive
      psychological states including anhedonia, impaired cognition, and fatigue. Under
      certain circumstances the psychological processes that promote salt intake can
      become powerful enough to cause "salt gluttony," or salt intake far in excess of
      physiological need. The present review discusses three aspects of the
      biopsychology of salt hunger and sodium deficiency: (1) the psychological
      processes that promote salt intake during sodium deficiency, (2) the effects of
      sodium deficiency on mood and cognition, and (3) the sensitization of sodium
      appetite as a possible cause of salt gluttony. 

PMID- 25572934
TI  - Erythropoietin ameliorates renal interstitial fibrosis via the inhibition of
      fibrocyte accumulation.
AB  - Erythropoietin (EPO) is a hematopoietic hormone that protects against renal
      interstitial fibrosis in animal models; however, the mechanism underlying the
      anti-fibrotic activity of EPO has remained elusive. The present study aimed to
      elucidate this mechanism. Twenty-four male C57BL6 mice were randomly divided into
      four groups, each comprising six mice: (i) control group (Sh); (ii) unilateral
      ureteral obstruction (UUO) plus vehicle group (U+V); (iii) UUO plus 300 U/kg body
      weight recombinant human (rh)EPO (U+E1) and (iv) UUO plus 1,000 U/kg body weight
      rhEPO (U+E2). Seven days post-surgery, the mice were sacrificed for examination.
      UUO induced significant deposition of extracellular matrix, detected by picro
      sirius red staining, which was decreased following rhEPO treatment. UUO also
      induced deposition of collagen I and fibronectin, rhEPO treatment was able to
      attenuate this effect at protein and mRNA levels. Compared with the control
      groups, UUO resulted in the accumulation of alpha-smooth muscle actin-positive
      cells in the interstitium, an effect which was ameliorated by rhEPO. Furthermore,
      rhEPO abrogated the UUO-induced increase in the number of bone marrow-derived
      myofibroblasts. Mechanistically, it was discovered that rhEPO decreased CXC
      chemokine ligand 16 (CXCL16) expression at protein level. However, treatment with
      rhEPO did not alter the protein expression of CC chemokine ligand 21 or CXCL12.
      These results suggested that rhEPO decreased fibrocyte accumulation via the
      suppression of renal CXCL16, which resulted in the attenuation of renal fibrosis.

PMID- 25572935
TI  - Transposable elements modulate human RNA abundance and splicing via specific RNA
      protein interactions.
AB  - BACKGROUND: Transposable elements (TEs) have significantly influenced the
      evolution of transcriptional regulatory networks in the human genome. Post
      transcriptional regulation of human genes by TE-derived sequences has been
      observed in specific contexts, but has yet to be systematically and
      comprehensively investigated. Here, we study a collection of 75 CLIP-Seq
      experiments mapping the RNA binding sites for a diverse set of 51 human proteins
      to explore the role of TEs in post-transcriptional regulation of human mRNAs and
      lncRNAs via RNA-protein interactions. RESULTS: We detect widespread interactions
      between RNA binding proteins (RBPs) and many families of TE-derived sequence in
      the CLIP-Seq data. Further, alignment coverage peaks on specific positions of the
      TE consensus sequences, illuminating a diversity of TE-specific RBP binding
      motifs. Evidence of binding and conservation of these motifs in the nonrepetitive
      transcriptome suggests that TEs have generally appropriated existing sequence
      preferences of the RBPs. Depletion assays for numerous RBPs show that TE-derived
      binding sites affect transcript abundance and splicing similarly to nonrepetitive
      sites. However, in a few cases the effect of RBP binding depends on the specific
      TE family bound; for example, the ubiquitously expressed RBP HuR confers
      transcript stability unless bound to an Alu element. CONCLUSIONS: Our meta
      analysis suggests a widespread role for TEs in shaping RNA-protein regulatory
      networks in the human genome.

PMID- 25572937
TI  - Cloning, characterization, and bacterial over-expression of an osmotin-like
      protein gene from Solanum nigrum L. with antifungal activity against three
      necrotrophic fungi.
AB  - A new osmotin-like protein gene from Solanum nigrum L. var indica (SindOLP) was
      cloned and overexpressed in Escherichia coli. The full-length intron-less gene is
      744 bp, encoding a mature protein of 247 amino acids with a molecular mass of 26
      kDa. The protein has an N-terminal cleavable signal sequence of 21 amino acids.
      There is the Thaumatin family signature pattern, with one each of amidation, N
      myristoylation, casein kinase II phosphorylation, tyrosine kinase
      phosphorylation, and protein kinase C phosphorylation sites. Hydropathy plot
      showed that it has six transmembrane helices. It has antifungal activity and can
      permeabilize fungal hyphae and spores. SindOLP is most active at pH 8, 25 
      degrees C and its antifungal activity is retained after 75  degrees C for 30 min.
      SindOLP inhibits fungal spore germination. The protein however lacks glucanase
      activity. The potential for SindOLP in developing fungus-resistant, transgenic
      crops is discussed.

PMID- 25572936
TI  - Prevalence and genetic characteristics of Saffold cardiovirus in China from 2009
      to 2012.
AB  - The epidemiology and clinical features of the Saffold cardiovirus (SAFV) remain
      ambiguous. The present study was designed to systematically and intensively
      investigate the epidemiological features of SAFV in pediatric patients in China.
      Three cohorts of pediatric patients were recruited from 2009 to 2012. Cohort 1
      comprised patients with acute respiratory tract infections. Cohort 2 comprised
      patients with diarrhea. Cohort 3 comprised hand, foot, and mouth disease (HFMD)
      patients. A total of 115 patients (1.6%) among 6052 (17/1647, 12/2013, and
      86/2392 in cohorts 1, 2, and 3, respectively) were SAFV-positive. The samples
      from 82 SAFV-positive patients were successfully sequenced, and four genotypes
      were identified: 8 SAFV-1, 41 SAFV-2, 29 SAFV-3, and 4 SAFV-6. A significantly
      higher detection rate was found in the HFMD patients than in other two cohorts
      (both P <0.001). A higher frequency of severe clinical outcome and nervous system
      manifestation were also observed in the SAFV-positive HFMD patients.
      Additionally, 6 (3.5%) cerebrospinal fluid and 7 (2.2%) serum samples from the
      HFMD-associated encephalitis patients were SAFV-positive. Based on the VP1
      sequences, all four genotypes displayed distinct geographical clustering. SAFV
      infection might be associated with a wide clinical spectrum and contribute to
      HFMD. 

PMID- 25572938
TI  - Tannase sequence from a xerophilic Aspergillus niger Strain and production of the
      enzyme in Pichia pastoris.
AB  - Tannin acyl hydrolases, or tannases (EC 3.1.1.20), are enzymes with potential
      biotechnological applications. In this work, we describe the gene and amino acid
      sequences of the tannase from Aspergillus niger GH1. In addition, we engineered
      Pichia pastoris strains to produce and secrete the enzyme, and the produced
      tannase was characterized biochemically. The nucleotide sequence of mature
      tannase had a length of 1,686 bp, and encodes a protein of 562 amino acids. A
      molecular model of mature A. niger GH1 tannase showed the presence of two
      structural domains, one with an alpha/beta-hydrolase fold and one lid domain that
      covers the catalytic site, likely being residues Ser-196, Asp-448, and His-494
      the putative catalytic triad, which are connected by a disulfide bond between the
      neighboring cysteines, Cys-195 and Cys-495. A 120-ml shake flask culture with a
      constructed recombinant P. pastoris strain showed extracellular tannase activity
      at 48 h induction of 0.57 U/ml. The produced tannase was N-glycosylated,
      consisted of two subunits, likely linked by a disulfide bond, and had an optimum
      pH of 5.0 and optimum temperature of 20  degrees C. These biochemical properties
      differed from those of native A. niger GH1 tannase. The recombinant tannase could
      be suitable for food and beverage applications.

PMID- 25572940
TI  - Can robotic surgery be done efficiently while training residents?
AB  - INTRODUCTION: Robotic surgery is a rapidly growing area in surgery. In an era of
      emphasis on cost reduction, the question becomes how do you train residents in
      robotic surgery? The aim of this study was to determine if there was a difference
      in operative time and complications when comparing general surgery residents
      learning robotic cholecystectomies to those learning standard laparoscopic
      cholecystectomies. METHODS: A retrospective analysis of adult patients undergoing
      robotic and laparoscopic cholecystectomy by surgical residents between March 2013
      and February 2014 was conducted. Demographic data, operative factors, length of
      stay (LOS), and complications were examined. Univariate and multivariate analyses
      were performed. The significance was set at p < 0.05. RESULTS: A total of 58
      patients were included in the study (18 in the robotic cholecystectomy group and
      40 in the laparoscopic group). Age, diagnosis, and American Society of
      Anesthesiologists score were not significantly different between groups. There
      was only 1 complication in the standard laparoscopic group in which a patient had
      to be taken back to surgery because of an incarcerated port site. LOS was
      significantly higher in the standard laparoscopic group (mean = 2.28) than in the
      robotic group (mean = 0.56; p < 0.0001). Operating room (OR) time was not
      statistically different between the standard laparoscopic group (mean = 90.98
      minutes) and the robotic group (mean = 97.00 minutes; p = 0.4455). When
      intraoperative cholangiogram was evaluated, OR time was shorter in the robotic
      group. CONCLUSION: Robotic training in general surgery residency does not amount
      to extra OR time. LOS in our study was significantly longer in the standard
      laparoscopic group.

PMID- 25572939
TI  - Carrot cells: a pioneering platform for biopharmaceuticals production.
AB  - Carrot (Daucus carota L.) is of importance in the molecular farming field as it
      constitutes the first plant species approved to produce biopharmaceuticals for
      human use. In this review, features that make carrot an advantageous species in
      the molecular farming field are analyzed and a description of the developments
      achieved with this crop thus far is presented. A guide for genetic transformation
      procedures is also included. The state of the art comprises ten vaccine
      prototypes against Measles virus, Hepatitis B virus, Human immunodeficiency
      virus, Yersinia pestis, Chlamydia trachomatis, Mycobacterium tuberculosis,
      enterotoxigenic Escherichia coli, Corynebacterium diphtheria/Clostridium
      tetani/Bordetella pertussis, and Helicobacter pylori; as well as the case of the
      glucocerebrosidase, an enzyme used for replacement therapy, and other
      therapeutics. Perspectives for these developments are envisioned and innovations
      are proposed such as the use of transplastomic technologies-, hairy roots-, and
      viral expression-based systems to improve yields and develop new products derived
      from this advantageous plant species. 

PMID- 25572941
TI  - Patient attitudes toward resident participation in cosmetic vs reconstructive
      outpatient consultations.
AB  - OBJECTIVES: The goal of residency programs is to provide trainees with exposure
      to all aspects of their chosen field so that they exit the program ready to be
      independent practitioners. However, it is common in some plastic surgery
      residency training programs to exclude residents from participation in
      consultations with patients who are seeking cosmetic surgery. The purpose of this
      study was to determine whether cosmetic surgery patients had a different view
      about resident involvement than reconstructive surgery patients and to evaluate
      what factors might be linked to patient attitudes on this topic. METHODS: 
      PARTICIPANTS: All new patients older than 18 years presenting to either academic
      or nonacademic locations were asked to complete the voluntary survey at their
      initial consultation. SETTING: The study was conducted at both the Ohio State
      University (academic) and Advanced Aesthetic and Laser Surgery (private practice)
      in Columbus, Ohio. DESIGN: The survey asked patients to identify their surgical
      concern as either cosmetic or reconstructive and to indicate the location on
      their body where they were having surgery. Additionally, a series of statements
      regarding resident involvement was presented with a 5-point Likert-type rating
      system to assess each patient's attitudes about a range of factors, such as
      resident sex and seniority. RESULTS: In total, 119 patients participated in the
      study by completing the survey. Of this population, 59.7% (n = 71) were
      classified as reconstructive surgery patients and 40.3% (n = 48) were classified
      as cosmetic surgery patients. Based on responses, it was determined that
      reconstructive surgery patients were more approving of resident involvement in
      their care than cosmetic surgery patients were. When other factors were analyzed,
      the patients seeking breast surgery were found to be more apprehensive about
      resident participation than non-breast surgery patients were. CONCLUSION:
      Although there were some differences in the way resident participation was
      perceived by cosmetic and reconstructive surgery patient populations, neither
      group strongly believed that resident participation decreased the quality of
      patient care. Based on these findings, plastic surgery training programs should
      begin to allow residents to become more involved in the care of cosmetic surgery
      patients.

PMID- 25572943
TI  - Recombination-aware alignment of diploid individuals.
AB  - BACKGROUND: Traditionally biological similarity search has been studied under the
      abstraction of a single string to represent each genome. The more realistic
      representation of diploid genomes, with two strings defining the genome, has so
      far been largely omitted in this context. With the development of sequencing
      techniques and better phasing routines through haplotype assembly algorithms, we
      are not far from the situation when individual diploid genomes could be
      represented in their full complexity with a pair-wise alignment defining the
      genome. RESULTS: We propose a generalization of global alignment that is designed
      to measure similarity between phased predictions of individual diploid genomes.
      This generalization takes into account that individual diploid genomes evolve
      through a mutation and recombination process, and that predictions may be
      erroneous in both dimensions. Even though our model is generic, we focus on the
      case where one wants to measure only the similarity of genome content allowing
      free recombination. This results into efficient algorithms for direct application
      in (i) evaluation of variation calling predictions and (ii) progressive multiple
      alignments based on labeled directed acyclic graphs (DAGs) to represent profiles.
      The latter may be of more general interest, in connection to covering alignment
      of DAGs. Extensions of our model and algorithms can be foreseen to have
      applications in evaluating phasing algorithms, as well as more fundamental role
      in phasing child genome based on parent genomes.

PMID- 25572942
TI  - When experts are oceans apart: comparing expert performance values for
      proficiency-based laparoscopic simulator training.
AB  - BACKGROUND: Surgical training is moving away from the operating room toward
      simulation-based skills training facilities. This has led to the development of
      proficiency-based training courses in which expert performance data are used for
      feedback and assessment. However, few expert value data sets have been published,
      and no standard method for generating expert values has been adopted by the
      field. METHODS: To investigate the effect of different proficiency value data
      sets on simulator training courses, we (1) compared 2 published expert
      performance data sets for the LapSim laparoscopic virtual-reality simulator (by
      van Dongen et al. and Heinrichs et al.) and (2) assessed the effect of using
      either set on LapSim training data obtained from 16 local residents in surgery
      and gynecology. RESULTS: Across all simulator tasks, the experts consulted by van
      Dongen et al. performed better on motion efficiency, but not on duration or
      damage control. Applying both proficiency sets to training data collected during
      a basic skills laparoscopic simulator course, residents would have graduated on
      an average in 1.5 fewer sessions using the Heinrichs expert values compared with
      the van Dongen expert values. CONCLUSIONS: The selection of proficiency values
      for proficiency-based simulator training courses affects training length, skills
      level assessment, and training costs. Standardized, well-controlled methods are
      necessary to create valid and reliable expert values for use in training and
      research.

PMID- 25572944
TI  - T helper 2 polarization in senile erythroderma with elevated levels of TARC and
      IgE.
AB  - BACKGROUND: Some cases of senile erythroderma tend to be diagnosed as senile
      atopic dermatitis (AD) based on elevated levels of immunoglobulin E (IgE) and
      thymus and activation-regulated chemokine (TARC). However, there are few studies
      that describe the detailed characteristics of senile erythroderma and senile AD.
      OBJECTIVE: We examined the association of erythroderma with AD. METHODS: In this
      retrospective observational study, 68 patients over 65 years of age who presented
      with erythroderma at Osaka University Hospital were enrolled. Patient data were
      collected through medical records and descriptive statistics. RESULTS: 47% of the
      patients were classified as having idiopathic erythroderma and 53% as having
      secondary erythroderma. In both idiopathic and secondary senile erythroderma
      patients, serum IgE and TARC levels were elevated. 84% of idiopathic erythroderma
      patients fulfilled the Japanese Dermatological Associations criteria for AD;
      however, only 4 patients were finally definitely diagnosed with senile AD.
      CONCLUSION: Many senile erythroderma patients showed AD-like symptoms due to T
      helper 2 polarization.

PMID- 25572946
TI  - Carotid plaque characterization using 3D T1-weighted MR imaging with
      histopathologic validation: a comparison with 2D technique.
AB  - BACKGROUND AND PURPOSE: 3D FSE T1WI has recently been used for carotid plaque
      imaging, given the potential advantages in contrast and spatial resolutions.
      However, its diagnostic performance remains unclear. Hence, we compared the
      ability of this technique to readily assess plaque characteristics with that of
      conventional images and validated the results with histologic classification.
      MATERIALS AND METHODS: We prospectively examined 34 patients with carotid
      stenosis who underwent carotid endarterectomy by using 1.5T scanners and obtained
      3D-FSE T1WI and 2D spin-echo T1WI scans. After generating reformatted images
      obtained from the 3D-FSE T1-weighted images, we calculated the contrast ratios
      for the plaques and the adjacent muscles and compared these findings with the
      pathologic classifications. RESULTS: Carotid plaques were histologically
      classified as types VII, VIII, IV-V, or VI. With 3D-FSE T1WI, the range of
      contrast ratios for each classification was the following: 0.94-0.97 (median,
      0.95), 0.95-1.29 (median, 1.10), 1.33-1.54 (median, 1.42), and 1.53-2.12 (median,
      1.80), respectively. With 2D imaging, the range of contrast ratios for each
      classification was the following: 0.79-1.02 (median, 0.90), 0.88-1.19 (median,
      1.01), 1.17-1.46 (median, 1.23), and 1.55-2.51 (median, 2.07), respectively.
      Results were significantly different among the 4 groups (P < .001). Sensitivity
      and specificity for discriminating vulnerable plaques (IV-VI) from stable plaques
      (VII, VIII) were both 100% for the 3D technique and 100% and 91%, respectively,
      for the 2D technique. CONCLUSIONS: 3D-FSE T1WI accurately characterizes
      intraplaque components of the carotid artery, with excellent sensitivity and
      specificity compared with those of 2D-T1WI.

PMID- 25572947
TI  - Contribution and additional impact of imaging to the SPAN-100 score.
AB  - BACKGROUND AND PURPOSE: Stroke Prognostication by Using Age and NIHSS score (SPAN
      100 index) facilitates stroke outcomes. We assessed imaging markers associated
      with the SPAN-100 index and their additional impact on outcome determination.
      MATERIALS AND METHODS: Of 273 consecutive patients with acute ischemic stroke
      (<4.5 hours), 55 were characterized as SPAN-100-positive (age +NIHSS score >=
      100). A comprehensive imaging review evaluated differences, using the presence of
      the hyperattenuated vessel sign, ASPECTS, clot burden score, collateral score,
      CBV, CBF, and MTT. The primary outcome assessed was favorable outcome (mRS <= 2).
      Secondary outcomes included recanalization, lack of neurologic improvement, and
      hemorrhagic transformation. Uni- and multivariate analyses assessed factors
      associated with favorable outcome. Area under the curve evaluated predictors of
      favorable clinical outcome. RESULTS: Compared with the SPAN-100-negative group,
      the SPAN-100-positive group (55/273; 20%) demonstrated larger CBVs (<0.001),
      poorer collaterals (P < .001), and increased hemorrhagic transformation rates
      (56.0% versus 36%, P = .02) despite earlier time to rtPA (P = .03). Favorable
      outcome was less common among patients with SPAN-100-positive compared with SPAN
      100-negative (10.9% versus 42.2%; P < .001). Multivariate regression revealed
      poorer outcome for SPAN-100-positive (OR = 0.17; 95% CI, 0.06-0.38; P = .001),
      clot burden score (OR = 1.14; 95% CI, 1.05-1.25; P < .001), and CBV (OR = 0.58;
      95% CI, 0.46-0.72; P = .001). The addition of the clot burden score and CBV
      improved the predictive value of SPAN-100 alone for favorable outcome from 60% to
      68% and 74%, respectively. CONCLUSIONS: SPAN-100-positivity predicts a lower
      likelihood of favorable outcome and increased hemorrhagic transformation. CBV and
      clot burden score contribute to poorer outcomes among high-risk patients and
      improve stroke-outcome prediction.

PMID- 25572945
TI  - Glial cell line-derived neurotrophic factor-mediated enhancement of noradrenergic
      descending inhibition in the locus coeruleus exerts prolonged analgesia in
      neuropathic pain.
AB  - BACKGROUND AND PURPOSE: The locus coeruleus (LC) is the principal nucleus
      containing the noradrenergic neurons and is a major endogenous source of pain
      modulation in the brain. Glial cell line-derived neurotrophic factor (GDNF), a
      well-established neurotrophic factor for noradrenergic neurons, is a major pain
      modulator in the spinal cord and primary sensory neurons. However, it is unknown
      whether GDNF is involved in pain modulation in the LC. EXPERIMENTAL APPROACH:
      Rats with chronic constriction injury (CCI) of the left sciatic nerve were used
      as a model of neuropathic pain. GDNF was injected into the left LC of rats with
      CCI for 3 consecutive days and changes in mechanical allodynia and thermal
      hyperalgesia were assessed. The alpha2 -adrenoceptor antagonist yohimbine was
      injected intrathecally to assess the involvement of descending inhibition in GDNF
      mediated analgesia. The MEK inhibitor U0126 was used to investigate whether the
      ERK signalling pathway plays a role in the analgesic effects of GDNF. KEY
      RESULTS: Both mechanical allodynia and thermal hyperalgesia were attenuated 24 h
      after the first GDNF injection. GDNF increased the noradrenaline content in the
      dorsal spinal cord. The analgesic effects continued for at least 3 days after the
      last injection. Yohimbine abolished these effects of GDNF. The analgesic effects
      of GDNF were partly, but significantly, inhibited by prior injection of U0126
      into the LC. CONCLUSIONS AND IMPLICATIONS: GDNF injection into the LC exerts
      prolonged analgesic effects on neuropathic pain in rats by enhancing descending
      noradrenergic inhibition.

PMID- 25572948
TI  - Anterior choroidal artery patency and clinical follow-up after coverage with the
      pipeline embolization device.
AB  - BACKGROUND AND PURPOSE: Endoluminal reconstruction with the Pipeline Embolization
      Device is an effective treatment option for select intracranial aneurysms.
      However, concerns for the patency of eloquent branch arteries covered by the
      Pipeline Embolization Device have been raised. We aimed to examine the patency of
      the anterior choroidal artery and clinical sequelae after ICA aneurysm treatment.
      MATERIALS AND METHODS: We prospectively analyzed all patients among our first 157
      patients with ICA aneurysms treated by the Pipeline Embolization Device who
      required placement of at least 1 device across the ostium of the anterior
      choroidal artery. The primary outcome measure was angiographic patency of the
      anterior choroidal artery at last follow-up. Age, sex, type of aneurysm,
      neurologic examination data, number of Pipeline Embolization Devices used,
      relationship of the anterior choroidal artery to the aneurysm, and completeness
      of aneurysm occlusion on follow-up angiograms were also analyzed. RESULTS: Twenty
      nine aneurysms requiring placement of at least 1 Pipeline Embolization Device
      (median = 1, range = 1-3) across the anterior choroidal artery ostium were
      identified. At angiographic follow-up (mean = 15.1 months; range = 12-39 months),
      the anterior choroidal artery remained patent, with antegrade flow in 28/29
      aneurysms (96.5%), while 24/29 (82.7%) of the target aneurysms were
      angiographically occluded by 1-year follow-up angiography. Anterior choroidal
      artery occlusion, with retrograde reconstitution of the vessel, was noted in a
      single case. A significant correlation between the origin of the anterior
      choroidal artery from the aneurysm dome and failure of the aneurysms to occlude
      following treatment was found. CONCLUSIONS: After placement of 36 Pipeline
      Embolization Devices across 29 anterior choroidal arteries (median = 1 device,
      range = 1-3 devices), 1 of 29 anterior choroidal arteries was found occluded on
      angiographic follow-up. The vessel occlusion did not result in persistent
      clinical sequelae. Coverage of the anterior choroidal artery origin with the
      Pipeline Embolization Device, hence, may be considered reasonably safe when
      deemed necessary for aneurysm treatment.

PMID- 25572950
TI  - Aneurysmal subarachnoid hemorrhage causes injury of the ascending reticular
      activating system: relation to consciousness.
AB  - BACKGROUND AND PURPOSE: Little is known about the pathogenetic mechanism of
      impaired consciousness following subarachnoid hemorrhage. Using diffusion tensor
      imaging, we attempted to investigate the presence of injury of the lower portion
      of the ascending reticular activating system between the pontine reticular
      formation and the intralaminar thalamic nuclei, and the relation between this
      injury and consciousness level in patients with SAH. MATERIALS AND METHODS: We
      recruited 24 consecutive patients with spontaneous SAH following aneurysmal
      rupture and 21 healthy control subjects. Consciousness level was rated by using
      the Glasgow Coma Scale. Using diffusion tensor tractography, we reconstructed the
      lower portion of the ascending reticular activating system between the pontine
      reticular formation and the intralaminar thalamic nuclei. Values of fractional
      anisotropy, apparent diffusion coefficient, and tract number of the ascending
      reticular activating system were measured. RESULTS: A significant difference in
      the tract number was observed between the patient and control groups (P < .05);
      however, there was no significant difference in terms of fractional anisotropy
      and apparent diffusion coefficient values (P > .05). In addition, regarding the
      tract number of the patient group, the Glasgow Coma Scale showed strong positive
      correlations with the tract number on the more affected side (r = 0.890, P <
      .05), the less affected side (r = 0.798, P < .05), and both sides (r = 0.919, P <
      .05), respectively. CONCLUSIONS: We found injury of the lower portion of the
      ascending reticular activating system between the pontine reticular formation and
      the thalamus in patients with SAH. In addition, we observed a close association
      between injury of the lower portion of the ascending reticular activating system
      and impaired consciousness in patients with SAH.

PMID- 25572949
TI  - Evaluating blood-brain barrier permeability in delayed cerebral infarction after
      aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Patients with SAH are at increased risk of delayed
      infarction. Early detection and treatment of delayed infarction remain
      challenging. We assessed blood-brain barrier permeability, measured as
      permeability surface area product, by using CTP in patients with SAH with delayed
      infarction. MATERIALS AND METHODS: We performed a retrospective study of patients
      with SAH with delayed infarction on follow-up NCCT. CTP was performed before the
      development of delayed infarction. CTP data were postprocessed into permeability
      surface area product, CBF, and MTT maps. Coregistration was performed to align
      the infarcted region on the follow-up NCCT with the corresponding location on the
      CTP maps obtained before infarction. Permeability surface area product, CBF, and
      MTT values were then obtained in the location of the subsequent infarction. The
      contralateral noninfarcted region was compared with the affected side in each
      patient. Wilcoxon signed rank tests were performed to determine statistical
      significance. Clinical data were collected at the time of CTP and at the time of
      follow-up NCCT. RESULTS: Twenty-one patients with SAH were included in the study.
      There was a statistically significant increase in permeability surface area
      product in the regions of subsequent infarction compared with the contralateral
      control regions (P < .0001). However, CBF and MTT values were not significantly
      different in these 2 regions. Subsequent follow-up NCCT demonstrated new delayed
      infarction in all 21 patients, at which time 38% of patients had new focal
      neurologic deficits. CONCLUSIONS: Our study reveals a statistically significant
      increase in permeability surface area product preceding delayed infarction in
      patients with SAH. Further investigation of early permeability changes in SAH may
      provide new insights into the prediction of delayed infarction.

PMID- 25572951
TI  - Clinical utility of arterial spin-labeling as a confirmatory test for suspected
      brain death.
AB  - Diagnosis of brain death is made on the basis of 3 essential findings: coma,
      absence of brain stem reflexes, and apnea. Although confirmatory tests are not
      mandatory in most situations, additional testing may be necessary to declare
      brain death in patients in whom results of specific components of clinical
      testing cannot be reliably evaluated. Recently, arterial spin-labeling has been
      incorporated as part of MR imaging to evaluate cerebral perfusion. Advantages of
      arterial spin-labeling include being completely noninvasive and providing
      information about absolute CBF. We retrospectively reviewed arterial spin
      labeling findings according to the following modified criteria based on
      previously established confirmatory tests to determine brain death: 1) extremely
      decreased perfusion in the whole brain, 2) bright vessel signal intensity around
      the entry of the carotid artery to the skull, 3) patent external carotid
      circulation, and 4) "hollow skull sign" in a series of 5 patients. Arterial spin
      labeling findings satisfied the criteria for brain death in all patients.
      Arterial spin-labeling imaging has the potential to be a completely noninvasive
      confirmatory test to provide additional information to assist in the diagnosis of
      brain death. 

PMID- 25572953
TI  - Downregulation of UHRF1 promotes EMT via inducing CXCR4 in human cancer cells.
AB  - Activation of epithelial-mesenchymal transition (EMT) is important for malignant
      tumor progression exhibiting migratory and invasive properties. UHRF1 (ubiquitin
      like, with PHD and RING finger domains 1), as an epigenetic regulator, plays a
      crucial role in DNA CpG methylation, chromatin remodeling and gene expression.
      Many studies demonstrated that UHRF1 is aberrantly expressed in various types of
      human cancer. However, the precise role of UHRF1 in human cancers remains highly
      controversial. In the present study, we found that downregulation of UHRF1
      enhances the migratory and invasive properties of human cancer cells by inducing
      EMT, and that the CXCR4 signaling pathway is strictly necessary for UHRF1
      deficiency-mediated induction of EMT. Downregulation of UHRF1 induced the
      expression of the EMT-regulating transcription factors, Zeb1, Slug and Snail and
      then led to decreased protein level of E-cadherin, and increased protein level of
      N-cadherin and vimentin, including increased migratory and invasive properties of
      human cancer cells. In addition, siRNA targeting of Zeb1 or Snail effectively
      attenuated UHRF1 deficiency-induced EMT, but siRNA targeting of Slug did not,
      indicating that Zeb1 and Snail play key roles in this event. Moreover,
      downregulation of UHRF1 induced the expression of CXCR4 in HepG2 cells. siRNA
      targeting of CXCR4 greatly suppressed the UHRF1 deficiency-induced EMT, as
      evidenced by a reversal of expression patterns of Snail and Zeb1, and by reduced
      migratory and invasive properties of HepG2 cells. In conclusion, our results
      demonstrate that downregulation of UHRF1 contributes to the induction of EMT in
      human cancer cells via the activation of CXCR4 signaling pathway. Our observation
      also suggests that UHRF1 may play a pivotal role in suppressing the malignant
      alteration of cancer cells.

PMID- 25572954
TI  - RIRS is equally efficient in patients with different BMI scores.
AB  - The objective of the study was to ascertain whether flexible ureteroscopy with
      holmium laser lithotripsy and/or extraction of stone fragments is as effective in
      obese patients as in non-obese patients. The patients were divided into four
      groups (group 1: normal weight = 79 procedures, group 2: overweight = 123
      procedures, group 3: obese = 87 procedures, and group 4: morbidly obese = 20
      procedures) according to BMI cohorts. Patient charts were retrospectively
      reviewed and relevant data collected. A total of 309 operations were included in
      the present study. The overall mean +/- SD (range) age was 41 +/- 12 years (18
      82), BMI 29 +/- 6 kg/m(2) (18-52), operative time 64 +/- 29 min (20-200),
      hospital stay 25 +/- 11 h (4-168), stone number 3 +/- 2 (1-15), stone burden 21
      +/- 14 mm (4-98), and internal stenting time 26 +/- 8 days (2-60). Mean stone
      size was 10 +/- 6, 9 +/- 5, 11 +/- 8, and 11 +/- 8 mm for groups 1 through 4,
      respectively. There were no differences among groups regarding patients and stone
      characteristics, and perioperative parameters including patient age, operative
      time, hospital stay, and complications. Overall SFRs were similar between groups
      (81, 87, 87.4, and 85%, respectively; chi(2)=3.304, p=0.770) as were the
      complication rates (12-16%). Our contemporary Retrograde Intrarenal Surgery
      (RIRS) series showed that operative times, hospital stays, ancillary equipment
      use (internal stent, basket, etc.), SFRs, and complication rates were independent
      of BMI. Therefore, RIRS can be performed as efficiently and efficaciously in
      obese patients as in non-obese patients.

PMID- 25572952
TI  - Neurovascular manifestations in hereditary hemorrhagic telangiectasia: imaging
      features and genotype-phenotype correlations.
AB  - BACKGROUND AND PURPOSE: Hereditary hemorrhagic telangiectasia is an autosomal
      dominant disease that presents in 10%-20% of patients with various brain vascular
      malformations. We aimed to report the radiologic features (phenotype) and the
      genotype-phenotype correlations of brain vascular malformations in hereditary
      hemorrhagic telangiectasia. MATERIALS AND METHODS: Demographic, clinical,
      genotypic, and imaging information of 75 patients with hereditary hemorrhagic
      telangiectasia with brain arteriovenous malformations enrolled in the Brain
      Vascular Malformation Consortium from 2010 to 2012 were reviewed. RESULTS:
      Nonshunting, small, superficially located conglomerates of enhancing vessels
      without enlarged feeding arteries or draining veins called "capillary vascular
      malformations" were the most commonly observed lesion (46 of 75 patients; 61%),
      followed by shunting "nidus-type" brain AVMs that were typically located
      superficially with a low Spetzler-Martin Grade and a small size (32 of 75
      patients; 43%). Direct high-flow fistulous arteriovenous shunts were present in 9
      patients (12%). Other types of vascular malformations (dural AVF and
      developmental venous anomalies) were present in 1 patient each. Multiplicity of
      vascular malformations was seen in 33 cases (44%). No statistically significant
      correlation was observed between hereditary hemorrhagic telangiectasia gene
      mutation and lesion type or lesion multiplicity. CONCLUSIONS: Depending on their
      imaging features, brain vascular malformations in hereditary hemorrhagic
      telangiectasia can be subdivided into brain AVF, nidus-type AVM, and capillary
      vascular malformations, with the latter being the most common phenotype in
      hereditary hemorrhagic telangiectasia. No genotype-phenotype correlation was
      observed among patients with this condition.

PMID- 25572955
TI  - Is micro-percutaneous nephrolithotomy surgery technically feasible and efficient
      under spinal anesthesia?
AB  - The objective of the study was to present the clinical and operative effects of
      two types of anesthesia on micro-percutaneous nephrolithotomy ("microperc"). We
      retrospectively reviewed 116 patients who underwent microperc between August 2011
      and September 2013. Patients were sorted into one of the two groups according to
      the type of anesthesia received: general (Group 1, n:53) or spinal (Group 2,
      n:63). Perioperative variables (age, stone size, location) and outcomes
      (operation time, success, complication rate) were evaluated and compared.
      Although there was a statistically significant difference in the mean age of
      patients (30.3 +/- 22.1 vs. 45.8 +/- 14.6, respectively, p < 0.001), mean body
      mass indexes were similar (p = 0.689). There was no substantial difference in
      terms of sizes and localizations of stones in the two groups (p = 0.970 and p =
      0.795). While a significant difference was found in comparison of operative times
      (59.62 +/- 32.56 vs. 40.98 +/- 26.45 min, p < 0.001), there was no statistically
      significant difference in mean fluoroscopy times (124.92 +/- 84.2 vs. 105.2 +/-
      61.0 s, p = 0.441). Stone-free rates were similar (90.5% vs. 93.6%, p = 0.297).
      We found no statistical differences between the two groups with respect to mean
      hemoglobin drop and hospitalization time (p = 0.015 and p = 0.917, respectively).
      The complication rates and analog pain scores were also similar (p = 0.543 and p
      = 0.365). Our results show that microperc is a feasible surgical modality in the
      treatment of kidney stone disease under both spinal and general anesthesia.
      Spinal anesthesia may be considered for patients at a high risk for general
      anesthesia, and also may be an alternative for patients who are concerned about
      and/or fearful of general anesthesia.

PMID- 25572956
TI  - Resilience in community: a social ecological development model for young adult
      sexual minority women.
AB  - Family support and rejection are associated with health outcomes among sexual
      minority women (SMW). We examined a social ecological development model among
      young adult SMW, testing whether identity risk factors or outness to family
      interacted with family rejection to predict community connectedness and
      collective self-esteem. Lesbian and bisexual women (N = 843; 57% bisexual)
      between the ages of 18-25 (M = 21.4; SD = 2.1) completed baseline and 12-month
      online surveys. The sample identified as White (54.2%), multiple racial
      backgrounds (16.6%), African American (9.6%) and Asian/Asian American (3.1%);
      10.2% endorsed a Hispanic/Latina ethnicity. Rejection ranged from 18 to 41%
      across family relationships. Longitudinal regression indicated that when outness
      to family increased, SMW in highly rejecting families demonstrated resilience by
      finding connections and esteem in sexual minority communities to a greater extent
      than did non-rejected peers. But, when stigma concerns, concealment motivation,
      and other identity risk factors increased over the year, high family rejection
      did not impact community connectedness and SMW reported lower collective self
      esteem. Racial minority SMW reported lower community connectedness, but not lower
      collective self-esteem. Families likely buffer or exacerbate societal risks for
      ill health. Findings highlight the protective role of LGBTQ communities and
      normative resilience among SMW and their families.

PMID- 25572958
TI  - Synthesis of phosphinoferrocene amides and thioamides from carbamoyl chlorides
      and the structural chemistry of Group 11 metal complexes with these mixed-donor
      ligands.
AB  - The reaction of in situ generated 1'-(diphenylphosphino)-1-lithioferrocene with
      carbamoyl chlorides, ClC(E)NMe2, affords the corresponding (thio)amides,
      Ph2PfcC(E)NMe2 (E = O (), S (); fc = ferrocene-1,1'-diyl). These compounds as
      well as their analogues, Ph2PfcC(O)NHMe () and Ph2PfcC(O)NH2 (), prepared from 1'
      (diphenylphosphino)ferrocene-1-carboxylic acid (Hdpf) were studied as ligands for
      the Group 11 metal ions. In the reactions with [Cu(MeCN)4][BF4], the amides give
      rise to bis-chelate complexes of the type [Cu(L-kappa(2)O,P)2][BF4]. Similar
      products, [Ag(L-kappa(2)O,P)2]ClO4, are obtained from silver(i) perchlorate and ,
      or . In contrast, the reaction of AgClO4 with produces a unique molecular dimer
      [Ag()(ClO4-kappaO)]2, where the metal centres are bridged by the sulfur atoms of
      the P,S-chelating thioamides. The reactions of with [AuCl(tht)] (tht =
      tetrahydrothiophene) afford the expected gold(i)-phosphine complexes, [AuCl(L
      kappaP)], containing uncoordinated (thio)amide moieties. Hemilabile coordination
      of the phosphinoamide ligands in complexes with the soft Group 11 metal ions is
      established by the crystal structure of a solvento complex, [Cu(-kappa(2)O,P)(
      kappaP)(CHCl3-kappaCl)][BF4], which was isolated serendipitously during an
      attempted crystallisation of [Cu(-kappa(2)O,P)2][BF4]. All of the compounds are
      characterised by spectroscopic methods, and the structures of several
      representatives of both the free phosphinoamides and their complexes are
      determined by X-ray diffraction analysis and further studied by DFT calculations
      and cyclic voltammetry. 

PMID- 25572959
TI  - Anti-platelet activity of water dispersible curcuminoids in rat platelets.
AB  - Curcuminoids are active principle of turmeric with plethora of health beneficial
      properties. In this study, we have evaluated for the first time the effect of
      water dispersible curcuminoids on rat platelet aggregation. Curcuminoids (10-30
      ug/mL) significantly inhibited platelet aggregation induced by agonists viz.,
      collagen, ADP and arachidonic acid. Curcuminoids were found to be two-fold more
      potent than curcumin in inhibiting platelet aggregation. Intracellular
      curcuminoid concentration was relatively higher than curcumin in rat platelets.
      Curcuminoids significantly attenuated thromboxane A2 , serotonin levels in rat
      platelets which play an important role in platelet aggregation. Curcuminoid
      treatment increased nitric oxide (NO) levels in platelets treated with agonists.
      Curcuminoids inhibited free radicals such as superoxide anion released from
      activated platelets, which ultimately inhibits platelet aggregation. Further,
      curcuminoids inhibited 12-lipoxygenase activity and formation of 12
      hydroperoxyeicosatetraenoic acid (12-HPETE) in activated rat platelets which
      regulates platelet aggregation. The results suggest that curcuminoids have
      remarkable anti-platelet activity by modulating multiple mechanisms involved in
      platelet aggregation. Thus curcuminoids may have a therapeutic potential to
      prevent platelet activation related disorders.

PMID- 25572957
TI  - Challenges in the Understanding and Treatment of Amyotrophic Lateral
      Sclerosis/Motor Neuron Disease.
AB  - With the acceleration in our understanding of ALS and the related motor neuron
      disease has come even greater challenges in reconciling all of the proposed
      pathogenic mechanisms and how this will translate into impactful treatments.
      Fundamental issues such as diagnostic definition(s) of the disease spectrum,
      relevant biomarkers, the impact of multiple novel genetic mutations and the
      significant effect of symptomatic treatments on disease progression are all areas
      of active investigation. In this review, we will focus on these key issues and
      highlight the challenges that confront both clinicians and basic science
      researchers.

PMID- 25572960
TI  - Engineering soya bean seeds as a scalable platform to produce cyanovirin-N, a non
      ARV microbicide against HIV.
AB  - There is an urgent need to provide effective anti-HIV microbicides to resource
      poor areas worldwide. Some of the most promising microbicide candidates are
      biotherapeutics targeting viral entry. To provide biotherapeutics to poorer
      areas, it is vital to reduce the cost. Here, we report the production of
      biologically active recombinant cyanovirin-N (rCV-N), an antiviral protein, in
      genetically engineered soya bean seeds. Pure, biologically active rCV-N was
      isolated with a yield of 350 MUg/g of dry seed weight. The observed amino acid
      sequence of rCV-N matched the expected sequence of native CV-N, as did the mass
      of rCV-N (11 009 Da). Purified rCV-N from soya is active in anti-HIV assays with
      an EC50 of 0.82-2.7 nM (compared to 0.45-1.8 nM for E. coli-produced CV-N).
      Standard industrial processing of soya bean seeds to harvest soya bean oil does
      not diminish the antiviral activity of recovered rCV-N, allowing the use of
      industrial soya bean processing to generate both soya bean oil and a recombinant
      protein for anti-HIV microbicide development. 

PMID- 25572962
TI  - Designing and tuning magnetic resonance with exchange interaction.
AB  - Exchange interaction at the interface between magnetic layers exhibits
      significant contribution to the magnetic resonance frequency. The in situ tuning
      of the resonance frequency, as large as 10 GHz, is demonstrated in a spintronics
      microwave device through manipulating the interface exchange interaction. 

PMID- 25572961
TI  - Expression patterns and prognostic role of transketolase-like 1 in muscle
      invasive bladder cancer.
AB  - PURPOSE: The pentose phosphate pathway (PPP) has been shown to play an important
      role in the metabolism of cancer cells. The transketolase-like 1 gene (TKTL1)
      encodes an enzyme representing an essential component of this pathway. Its
      expression has been demonstrated to correlate with stage and outcome in various
      tumors. The aim of the present study was to assess expression patterns and the
      prognostic role of TKTL1 in muscle-invasive bladder cancer (MIBC). PATIENTS AND
      METHODS: The expression of TKTL1 was assessed in a tissue microarray consisting
      of histopathologically benign and malign tissue of 112 patients who underwent
      radical cystectomy due to MIBC. Cytoplasmatic and nuclear expression were
      assessed by immunohistochemistry and compared separately with clinicopathologic
      parameters and outcome. RESULTS: Cytoplasmatic expression of TKTL1 was
      exclusively present in tumor tissue. In contrast, the proportion of nuclei
      positive for TKTL1 was higher in histopathologically benign tissue compared with
      malign tissue. No correlation was observed between cytoplasmatic or nuclear TKTL1
      expression and tumor stage, grade or the presence of metastases. Patients with
      lymph node involvement showed a decreased frequency of cytoplasmatic expression
      compared with node-negative patients (p = 0.01). However, no further correlation
      was observed between the expression of TKTL1 and clinical outcome of patients.
      CONCLUSIONS: The present study shows that the cytoplasmatic expression of TKTL1
      is specific for MIBC tissue compared with histopathologically benign urothelium.
      This specific expression is present in a subgroup of MIBC potentially identifying
      patients with activated PPP suitable for a targeted inhibition of sugar
      metabolism. In contrast to other malignancies, TKTL1 shows no prognostic
      significance in MIBC.

PMID- 25572965
TI  - Correction for Crockett et al., Harm to others outweighs harm to self in moral
      decision making.

PMID- 25572963
TI  - Regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and
      connective tissue homeostasis.
AB  - It is well known that angiogenesis is linked to fibrotic processes in
      fibroproliferative diseases, but insights into pathophysiological processes are
      limited, due to lack of understanding of molecular mechanisms controlling
      endothelial and fibroblastic homeostasis. We demonstrate here that the matrix
      receptor anthrax toxin receptor 1 (ANTXR1), also known as tumor endothelial
      marker 8 (TEM8), is an essential component of these mechanisms. Loss of TEM8
      function in mice causes reduced synthesis of endothelial basement membrane
      components and hyperproliferative and leaky blood vessels in skin. In addition,
      endothelial cell alterations in mutants are almost identical to those of
      endothelial cells in infantile hemangioma lesions, including activated VEGF
      receptor signaling in endothelial cells, increased expression of the downstream
      targets VEGF and CXCL12, and increased numbers of macrophages and mast cells. In
      contrast, loss of TEM8 in fibroblasts leads to increased rates of synthesis of
      fiber-forming collagens, resulting in progressive fibrosis in skin and other
      organs. Compromised interactions between TEM8-deficient endothelial and
      fibroblastic cells cause dramatic reduction in the activity of the matrix
      degrading enzyme MMP2. In addition to insights into mechanisms of connective
      tissue homeostasis, our data provide molecular explanations for vascular and
      connective tissue abnormalities in GAPO syndrome, caused by loss-of-function
      mutations in ANTXR1. Furthermore, the loss of MMP2 activity suggests that
      fibrotic skin abnormalities in GAPO syndrome are, in part, the consequence of
      pathophysiological mechanisms underlying syndromes (NAO, Torg and Winchester)
      with multicentric skin nodulosis and osteolysis caused by homozygous loss-of
      function mutations in MMP2. 

PMID- 25572966
TI  - Correction for Rietveld et al., Common genetic variants associated with cognitive
      performance identified using the proxy-phenotype method.

PMID- 25572967
TI  - Reply to Bada and Cleaves: Ab initio free-energy landscape of Miller-like
      prebiotic reactions.

PMID- 25572964
TI  - Causes of natural variation in fitness: evidence from studies of Drosophila
      populations.
AB  - DNA sequencing has revealed high levels of variability within most species.
      Statistical methods based on population genetics theory have been applied to the
      resulting data and suggest that most mutations affecting functionally important
      sequences are deleterious but subject to very weak selection. Quantitative
      genetic studies have provided information on the extent of genetic variation
      within populations in traits related to fitness and the rate at which variability
      in these traits arises by mutation. This paper attempts to combine the available
      information from applications of the two approaches to populations of the
      fruitfly Drosophila in order to estimate some important parameters of genetic
      variation, using a simple population genetics model of mutational effects on
      fitness components. Analyses based on this model suggest the existence of a class
      of mutations with much larger fitness effects than those inferred from sequence
      variability and that contribute most of the standing variation in fitness within
      a population caused by the input of mildly deleterious mutations. However,
      deleterious mutations explain only part of this standing variation, and other
      processes such as balancing selection appear to make a large contribution to
      genetic variation in fitness components in Drosophila. 

PMID- 25572968
TI  - Ab initio simulations and the Miller prebiotic synthesis experiment.

PMID- 25572969
TI  - Silencing of the ABCC4 gene by RNA interference reverses multidrug resistance in
      human gastric cancer.
AB  - The identification of genes associated with recurrent drug resistance in gastric
      cancer and the elucidation of the underlying molecular mechanisms associated with
      recurrent drug resistance in gastric cancer are important for the effective
      treatment and prognosis of this cancer. Variations in the expression level of the
      ATP-binding cassette subfamily C member 4 (ABCC4) gene are correlated with the
      recurrence, development and chemotherapeutic susceptibility of various types of
      cancers. In the present study, we demonstrated that the ABCC4 gene was highly
      expressed in multiple types of gastric cancer cells, and ABCC4 expression was
      even more prominent in the drug-resistant gastric cancer cells. Conversely, in
      normal gastric mucosal cells, ABCC4 expression was very low or undetectable. We
      used RNA interference to decrease the expression of ABCC4 in drug-resistant
      gastric cancer cells, which resulted in an increase in apoptosis and cell cycle
      arrest in the G1 phase. In addition, we found that ABCC4 knockdown in 5
      fluorouracil (5-FU)-resistant cancer cells restored 5-FU sensitivity, resulting
      in the inhibition of cell proliferation and tumour growth in nude mice. Our
      results showed that inhibition of ABCC4 gene expression can inhibit the
      proliferation of multidrug-resistant gastric cancer cells and can enhance gastric
      cancer cell sensitivity to chemotherapeutic drugs.

PMID- 25572970
TI  - [Navigation in urological surgery: Possibilities and limits of current
      techniques].
AB  - Surgical navigation describes the concept of real-time processing and
      presentation of preoperative and intraoperative data from different sources to
      intraoperatively provide surgeons with additional cognitive support. Imaging
      methods such as 3D ultrasound, magnetic resonance imaging (MRI) and computed
      tomography (CT) and data from optical, electromagnetic or mechanical tracking
      methods are used. The resulting information of the navigation system will be
      presented by the means of visual methods. Mostly virtual reality or augmented
      reality visualization is used. There are different guidance systems for various
      disciplines introduced. Mostly it operates on rigid structures (bone, brain). For
      soft tissue navigation motion compensation and deformation detection are
      necessary. Therefore, marker-based tracking methods are used in several
      urological application examples; however, the systems are often still under
      development and have not yet arrived in the clinical routine. 

PMID- 25572971
TI  - Suggestions for improving perihilar cholangiocarcinoma staging based on an
      evaluation of the seventh edition AJCC system.
AB  - The first separate staging system for perihilar cholangiocarcinoma was introduced
      by the seventh edition American Joint Committee on Cancer (AJCC) manual. To
      determine whether it strengthens the prognostic value, a comparative analysis
      with the sixth edition was performed, through which some areas for improvements
      were identified. The tumor-nodes-metastasis (TNM) stage and R status of 378
      operated perihilar cholangiocarcinoma patients between 1990 and 2011 were
      reviewed. Survival analyses were conducted. Although the stages were up-numbered
      from I to II and II to III, the sixth and seventh editions had intercorresponding
      stages providing similar classifications. Applying the seventh edition, 9.8% were
      downstaged and 1.3% upstaged. Several issues were identified. First, both
      editions did not discriminate node-free locally advanced resectable diseases and
      node-positive resectable diseases. Second, stages IVA and IVB in the seventh
      edition had different prognoses suggesting misclassification of stage IVA. Third,
      the prognosis of liver invasion (T2b) resembled that of T3 more than T2a in the
      seventh edition, warranting investigation into the downstaging of liver invasion.
      Lastly, curative resections were possible in some Bismuth type 4 tumors allowing
      for better survival, suggesting that classifying them as unresectable disease
      (T4) should be revised. A discrete staging for perihilar cholangiocarcinoma is
      necessary; however, some points need further clarifications.

PMID- 25572972
TI  - The surgical apgar score predicts postoperative ICU admission.

PMID- 25572973
TI  - Abdominal bone formation.
AB  - A 34-year-old man with a history of severe peritonitis was referred to the
      hospital for reconstruction of intestinal continuity. Preoperative CT scan
      revealed extensive heterotopic mesenteric ossification (HMO). Intestinal
      continuity was then reconstructed after complete removal of the enormous
      dendritic intraabdominal bone formation. The exact etiology of HMO remains
      unknown. It is hypothesized to result from the dislocation of small osseous
      fragments from the xiphoid or os pubis as well as from osteogenic differentiation
      of local mesenchymal progenitor cells. 

PMID- 25572974
TI  - Improved quality of care for patients undergoing an abdominoperineal excision for
      rectal cancer.
AB  - INTRODUCTION: New diagnostics, the emergence of total mesorectal excision and
      neoadjuvant treatments have improved outcome for patients with rectal cancer.
      Patients with distal rectal cancer undergoing an abdominoperineal excision seem
      to do worse compared to those treated with sphinctersparing techniques. The aim
      of this study was to evaluate the quality of care for patients undergoing an
      abdominoperineal excision for distal rectal cancer during the last 15 years.
      MATERIALS AND METHODS: All patients with rectal cancer, who underwent an
      abdominoperineal excision between December 1996 and December 2010 in 5 Dutch
      hospitals were analysed. Patients were divided into three cohorts; 1996-2001,
      2001-2005 and 2006-2010. All data was extracted from medical records. RESULTS:
      477 patients were identified. There was no significant difference in sex, age,
      BMI, prior pelvic surgery and ASA stages between the cohorts. MRI became a
      standard tool in the work-up, the use increased from 4.5% in the first, to 95.1%
      in the last cohort (p < 0.0001). Neoadjuvant treatment shifted from predominantly
      none (64.9% in cohort 1) to short course radiotherapy (66.7% in cohort 2) and
      chemoradiation therapy (55.7% in cohort 3). There was a trend towards a decreased
      circumferential resection margin involvement in the cohorts (18.8%, 16.7% and
      11.4%; p = 0.142). Accidental bowel perforations have significantly decreased
      from 28.6%, and 21.7% to 9.2% in cohort 3 (p < 0.0001). CONCLUSION: Significant
      improvements in work-up, neoadjuvant and surgical treatment have been made for
      patients with low rectal cancer, undergoing an abdominoperineal excision. These
      improvements result in improved short term outcome.

PMID- 25572975
TI  - Endoscopic Treatment of Upper Gastrointestinal Obstruction After Ingestion of
      Illicit Drug Packets.

PMID- 25572976
TI  - A Model for Predicting Development of Overt Hepatic Encephalopathy in Patients
      With Cirrhosis.
AB  - BACKGROUND & AIMS: Overt hepatic encephalopathy (HE) affects patients' quantity
      and quality of life and places a burden on families. There is evidence that overt
      HE might be prevented pharmacologically, but prophylaxis would be justified and
      cost effective only for patients at risk. We aimed to identify patients with
      cirrhosis at risk for overt HE. METHODS: We collected data from October 2009
      through December 2012 for 216 consecutive patients with cirrhosis (based on liver
      biopsy, 96 patients with minimal HE), admitted to the Gastroenterology Unit at
      the University of Rome. Patients were followed up and evaluated for an average of
      14.7 +/- 11.6 months; development of overt HE was recorded. We analyzed end-stage
      liver disease scores, shunt placement, previous overt or minimal HE, psychometric
      hepatic encephalopathy score (PHES), and levels of albumin, bilirubin,
      creatinine, and sodium to develop a prediction model. We validated the model in
      112 patients with cirrhosis seen at the University of Padua and followed up for
      12 +/- 9.5 months. RESULTS: During the follow-up period, 68 patients (32%)
      developed at least 1 episode of overt HE. Based on multivariate analysis, the
      development of overt HE was associated with previous HE, minimal HE (based on
      PHES), and level of albumin less than 3.5 g/dL (area under curve [AUC], 0.74). A
      model that excluded minimal HE but included albumin level and previous HE also
      identified patients who would develop overt HE (AUC, 0.71); this difference in
      AUC values was not statistically significant (P = .104). Both models were
      validated in the independent group of patients (3 variables: AUC, 0.74; 95%
      confidence interval, 0.66-0.83; and 2 variables: AUC, 0.71; 95% confidence
      interval, 0.63-0.78). CONCLUSIONS: We developed and validated a model to identify
      patients with cirrhosis at risk for overt HE based on previous HE, albumin
      levels, and PHES. If PHES was not available, previous HE and albumin levels still
      can identify patients at risk. Psychometric evaluation is essential for patients
      with no history of HE. These findings should aid in planning studies of
      pharmacologic prevention of overt HE.

PMID- 25572977
TI  - Attenuation measurements show that the presence of a TachoSil surgical patch will
      not compromise target irradiation in intra-operative electron radiation therapy
      or high-dose-rate brachytherapy.
AB  - BACKGROUND: Surgery of locally advanced and/or recurrent rectal cancer can be
      complemented with intra-operative electron radiation therapy (IOERT) to deliver a
      single dose of radiation directly to the unresectable margins, while sparing
      nearby sensitive organs/structures. Haemorrhages may occur and can affect the
      dose distribution, leading to an incorrect target irradiation. The TachoSil (TS)
      surgical patch, when activated, creates a fibrin clot at the surgical site to
      achieve haemostasis. The aim of this work was to determine the effect of TS on
      the dose distribution, and ascertain whether it could be used in combination with
      IOERT. This characterization was extended to include high dose rate (HDR)
      intraoperative brachytherapy, which is sometimes used at other institutions
      instead of IOERT. METHODS: CT images of the TS patch were acquired for initial
      characterization. Dosimetric measurements were performed in a water tank phantom,
      using a conventional LINAC with a hard-docking system of cylindrical applicators.
      Percentage Depth Dose (PDD) curves were obtained, and measurements made at the
      depth of dose maximum for the three clinically used electron energies (6, 9 and
      12MeV), first without any attenuator and then with the activated patch of TS
      completely covering the tip of the IOERT applicator. For HDR brachytherapy, a
      measurement setup was improvised using a solid water phantom and a Farmer
      ionization chamber. RESULTS: Our measurements show that the attenuation of a
      TachoSil patch is negligible, both for high energy electron beams (6 to 12MeV),
      and for a HDR (192)Ir brachytherapy source. Our results cannot be extrapolated to
      lower beam energies such as 50 kVp X-rays, which are sometimes used for breast
      IORT. CONCLUSION: The TachoSil surgical patch can be used in IORT procedures
      using 6MeV electron energies or higher, or HDR (192)Ir brachytherapy.

PMID- 25572978
TI  - Assessment of anxiety in patients who undergo surgical procedures for tooth
      implants: a prospective study.
AB  - PURPOSE: The purpose of this study is to evaluate general anxiety using the State
      Trait Anxiety Inventory (STAI) and dental anxiety using the Corah Dental Anxiety
      Scale (Corah-DAS) in patients who underwent surgical procedures for dental
      implants. METHODS: The study was performed with 55 patients who underwent implant
      surgery, of whom 37 were treated at a university and 18 were treated at a private
      office. General anxiety (STAI) and dental anxiety (Corah-DAS) were assessed at
      three different time points: appointment prior to clinical procedures (T1), day
      of procedures (just before the procedures; T2), and first post-procedure
      appointment (T3). The data were analyzed using analysis of variance followed by
      the Duncan test or Student's t-test. RESULTS: State anxiety increased on the day
      of surgery (T2), whereas trait anxiety was higher at T1 (both p < 0.05). Women (n
      = 41) presented higher state anxiety at T2 than men (n = 14). Patients who were
      treated at the university (n = 37) exhibited higher state anxiety at both T1 and
      T3 than patients who were treated in a private practice (n = 18). Individuals
      with lower dental anxiety at T1 were those who reported having good experiences
      with dental treatment. CONCLUSIONS: An increase in state anxiety was observed
      immediately before surgical procedures, and this increase was more pronounced in
      females. Although the Corah-DAS has been used as an indicator of dental anxiety,
      the STAI appears to be more sensitive for the measurement of anxiety. The
      application of appropriate methods is essential for ascertaining anxiety in
      patients, which should be considered in oral surgeries.

PMID- 25572979
TI  - Midline upper lip sinus: a case report and review of literature.
AB  - PURPOSE: A multitude of developmental anomalies has been reported in the head and
      neck, especially on the face; however, cases of upper lip sinuses and fistulas
      have hardly been reported. METHOD: A 10-year-old girl presented with a
      recurrently discharging upper lip sinus. After adequate presurgical workup,
      excision of the lesion resulted in a clinical cure. RESULT: Literature review
      suggests a number of theories for the origin of the upper lip sinus; however,
      none have proven to be conclusive. CONCLUSION: Upper lip sinus formations are
      rare developmental events, and the pathogenesis of these lesions still needs
      further evaluation.

PMID- 25572980
TI  - [Atypical presentation of central retinal artery occlusion].

PMID- 25572981
TI  - Integrin alphavbeta3 is required for cathepsin B-induced hepatocellular carcinoma
      progression.
AB  - The cysteine protease cathepsin B (Cat B) is important in the progression of
      tumor cells, however, the function and molecular mechanisms of Cat B in
      hepatocellular carcinoma (HCC) remain to be elucidated. Our previous study
      demonstrated that integrin alphavbeta3 regulated the biological behavior of HCC.
      The present study demonstrated that Cat B was also important in cell
      proliferation and apoptosis in HCC. Notably, Cat B was observed to activate the
      phosphoinositide 3-kinase (PI3K)/Akt signaling pathway to promote HCC
      proliferation. Furthermore, inhibition of integrin alphavbeta3 significantly
      prevented Cat B-induced activation of PI3K/Akt and the progression of HCC. Thus,
      the results of the present study suggested the presence of a Cat B/integrin
      alphavbeta3/PI3K/Akt axis in the regulation of the progression of HCC.

PMID- 25572982
TI  - Rerouting the metabolic pathway of (18)F-labeled peptides: the influence of
      prosthetic groups.
AB  - Current translational cancer research is directed to the development of high
      affinity peptide ligands for targeting neuropeptide receptors overexpressed in
      different types of cancer. Besides their desired high binding affinity to the
      receptor, the suitability of radiolabeled peptides as targeting vectors for
      molecular imaging and therapy depends on additional aspects such as high tumor-to
      background ratio, favorable clearance pattern from nontarget tissue, and
      sufficient metabolic stability in vivo. This study reports how a switch from the
      prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB), to 2-deoxy
      2-[(18)F]fluoro-d-glucose ([(18)F]FDG) effects the metabolic pathway of an (18)F
      labeled bombesin derivative, QWAV-Sar-H-FA01010-Tle-NH2. (18)F-Labeled bombesin
      derivatives represent potent peptide ligands for selective targeting of gastrin
      releasing peptide (GRP) receptor-expressing prostate cancer. Radiosynthesis of
      (18)F-labeled bombesin analogues [(18)F]FBz-Ava-BBN2 and [(18)F]FDG-AOAc-BBN2 was
      achieved in good radiochemical yields of ~50% at a specific activity exceeding 40
      GBq/MUmol. Both nonradioactive compounds FBz-Ava-BBN2 and FDG-AOAc-BBN2 inhibited
      binding of [(125)I]Tyr(4)-bombesin(1-14) in PC3 cells with IC50 values of 9 and
      16 nM, respectively, indicating high inhibitory potency. Influence of each
      prosthetic group was further investigated in PC3 mouse xenografts using dynamic
      small animal PET imaging. In comparison to [(18)F]FBz-Ava-BBN2, total tumor
      uptake levels were doubled after injection of [(18)F]FDG-AOAc-BBN2 while renal
      elimination was increased. Blood clearance and in vivo metabolic stability were
      similar for both compounds. The switch from [(18)F]SFB to [(18)F]FDG as the
      prosthetic group led to a significant reduction in lipophilicity which resulted
      in more favorable renal clearance and increased tumor uptake. The presented
      single step radiolabeling-glycosylation approach represents an innovative
      strategy for site-directed peptide labeling with the short-lived positron emitter
      (18)F while providing a favorable pharmacokinetic profile of (18)F-labeled
      peptides.

PMID- 25572985
TI  - Back to the future: republishing Bradford Hill and more from our archive.

PMID- 25572983
TI  - Retrospective analysis of the clinicopathologic and prognostic characteristics of
      stage I placental site trophoblastic tumor in China.
AB  - OBJECTIVE: To investigate clinicopathologic features and identify prognostic
      factors of placental site trophoblastic tumor (PSTT). METHODS: In a retrospective
      study, data were analyzed from patients with stage I PSTT treated at a tertiary
      hospital in Shanghai, China, from January 2007 to May 2013. Univariate log-rank
      tests were used to examine the association between clinicopathologic
      characteristics and overall survival and disease-free survival (DFS). RESULTS: In
      total, seven patients had stage I PSTT. Mean age was 31.6 years (range 22-42).
      Four patients had term delivery as the outcome of their antecedent pregnancy. Six
      had a beta-human chorionic gonadotropin (beta-hCG) serum concentration of less
      than 10 000 mIU/mL. Among five patients who underwent hysterectomy combined with
      chemotherapy, one had recurrent disease. One patient received fertility
      preserving therapy and achieved complete remission. The mean 5-year overall
      survival and DFS were 100% and 86%, respectively. Maximum beta-HCG concentration
      of at least 10 000 mIU/mL and a mitotic index of more than 5 mitotic counts per
      10 high-power fields were associated with disease recurrence (both P=0.014).
      CONCLUSION: Pretreatment beta-hCG concentration and mitotic index might be
      predictors of recurrence among patients with PSTT. Fertility-preserving therapy
      might be practical in some patients.

PMID- 25572984
TI  - Maternal onset de novo SH2D1A mutation and lymphocytic choriomeningitis virus
      infection in a patient with X-linked lymphoproliferative disease type 1: a case
      report.
AB  - X-linked lymphoproliferative disease type 1 (XLP1) is a rare genetic
      immunodeficiency disease, which occurs due to germline mutations in the SH2D1A
      gene. This gene has been reported to encode the adaptor molecule signaling
      lymphocytic activation molecule-associated protein XLP1 is generally triggered by
      the Epstein-Barr virus (EBV) infection. The present study reported the case of a
      4-year-old male who presented with a high fever, hypogammaglobulinemia, diffuse
      lung disease and encephalitis. The patient was infected with the lymphocytic
      choriomeningitis virus (LCMV), not EBV or any other human herpes virus. The
      patient was found to carry a SH2D1A c.7G>T/p.A3S mutation, which was inherited
      from the mother and maternal grandfather, as well as a SH2D1A c.228T>A/p.Y76X
      mutation, which was identified to be a maternal-onset de novo mutation at the
      time of germline development of the patient's mother. To the best of our
      knowledge, the present study is the first reported case of maternal-onset XLP1
      with a de novo SH2D1A mutation and LCMV infection.

PMID- 25572987
TI  - The NHS celebrated.

PMID- 25572986
TI  - Association and causation in epidemiology - half a century since the publication
      of Bradford Hill's interpretational guidance.

PMID- 25572989
TI  - Evolution of evidence-based medicine to detect evidence mutations.

PMID- 25572990
TI  - Traumatic cardiac arrest.
AB  - Traumatic cardiac arrest is known to have a poor outcome, and some authors have
      stated that attempted resuscitation from traumatic cardiac arrest is futile.
      However, advances in damage control resuscitation and understanding of the
      differences in pathophysiology of traumatic cardiac arrest compared to medical
      cardiac arrest have led to unexpected survivors. Recently published data have
      suggested that outcome from traumatic cardiac arrest is no worse than that for
      medical causes of cardiac arrest, and in some groups may be better. This review
      highlights key areas of difference between traumatic cardiac arrest and medical
      cardiac arrest, and outlines a strategy for the management of patients in
      traumatic cardiac arrest. Standard Advanced Life Support algorithms should not be
      used for patients in traumatic cardiac arrest. 

PMID- 25572991
TI  - Influence of training changes on the stability of specialty choices of UK medical
      graduates: surveys of the graduates of 2002 and 2008.
AB  - OBJECTIVES: To explore the impact of Modernising Medical Careers (MMC) training
      on the stability of medical career choices in the UK. SETTING UK PARTICIPANTS:
      Graduates of 2002 and 2008 from all UK medical schools, 1 and 3 years
      postgraduation. DESIGN: Questionnaire surveys were conducted of 2002 and 2008
      graduates from all UK medical schools 1 and 3 years post graduation. MAIN OUTCOME
      MEASURES: Doctors gave their specialty choice(s) and rated the influence of each
      of 11 factors on their career choice. RESULTS: 2008 graduates were a little more
      likely than graduates of 2002 to retain their year 1 choice in year 3 (77.3% vs.
      73.3%; p = 0.002). Among 2008 graduates, the percentage retaining their year 1
      choice varied between 42% (clinical oncology) and 79% (general practice).
      Enthusiasm for a specialty, student experience and inclinations before medical
      school were associated with choice retention; consideration of domestic
      circumstances and hours/working conditions were associated with changes of
      choice. 2008 graduates were more likely than 2002s to be influenced by enthusiasm
      for a specialty, self-appraisal of their skills, working hours and their domestic
      circumstances; and less likely to be influenced by their experience of jobs, a
      particular teacher/department or eventual financial prospects. CONCLUSIONS: Post
      MMC, graduates were less likely to change their career choice and more likely to
      be motivated by personal factors and self-assessment of their suitability to a
      particular area of work.

PMID- 25572992
TI  - Meta-analyse en medecine: the first book on systematic reviews in medicine.

PMID- 25572993
TI  - The environment and disease: association or causation? 1965.

PMID- 25572997
TI  - Testing the limits of rational design by engineering pH sensitivity into membrane
      active peptides.
AB  - In this work, we sought to rationally design membrane-active peptides that are
      triggered by low pH to form macromolecular-sized pores in lipid bilayers. Such
      peptides could have broad utility in biotechnology and in nanomedicine as cancer
      therapeutics or drug delivery vehicles that promote release of macromolecules
      from endosomes. Our approach to rational design was to combine the properties of
      a pH-independent peptide, MelP5, which forms large pores allowing passage of
      macromolecules, with the properties of two pH-dependent membrane-active peptides,
      pHlip and GALA. We created two hybrid sequences, MelP5_Delta4 and MelP5_Delta6,
      by using the distribution of acidic residues on pHlip and GALA as a guide to
      insert acidic amino acids into the amphipathic helix of MelP5. We show that the
      new peptides bind to lipid bilayers and acquire secondary structure in a pH
      dependent manner. The peptides also destabilize bilayers in a pH-dependent
      manner, such that lipid vesicles release the small molecules ANTS/DPX at low pH
      only. Thus, we were successful in designing pH-triggered pore-forming peptides.
      However, no macromolecular release was observed under any conditions. Therefore,
      we abolished the unique macromolecular poration properties of MelP5 by
      introducing pH sensitivity into its sequence. We conclude that the properties of
      pHlip, GALA, and MelP5 are additive, but only partially so. We propose that this
      lack of additivity is a limitation in the rational design of novel membrane
      active peptides, and that high-throughput approaches to discovery will be
      critical for continued progress in the field. 

PMID- 25572999
TI  - Inpatient admissions of patients living with HIV in two European centres (UK and
      Italy); comparisons and contrasts.

PMID- 25573000
TI  - Brain infarct and meningitis due to non-O1Vibrio cholerae.

PMID- 25572998
TI  - Assessment of critical exposure and outcome windows in time-to-event analysis
      with application to air pollution and preterm birth study.
AB  - In reproductive epidemiology, there is a growing interest to examine associations
      between air pollution exposure during pregnancy and the risk of preterm birth
      (PTB). One important research objective is to identify critical periods of
      exposure and estimate the associated effects at different stages of pregnancy.
      However, population studies have reported inconsistent findings. This may be due
      to limitations from the standard analytic approach of treating PTB as a binary
      outcome without considering time-varying exposures together over the course of
      pregnancy. To address this research gap, we present a Bayesian hierarchical model
      for conducting a comprehensive examination of gestational air pollution exposure
      by estimating the joint effects of weekly exposures during different vulnerable
      periods. Our model also treats PTB as a time-to-event outcome to address the
      challenge of different exposure lengths among ongoing pregnancies. The proposed
      model is applied to a dataset of geocoded birth records in the Atlanta
      metropolitan area between 1999-2005 to examine the risk of PTB associated with
      gestational exposure to ambient fine particulate matter [Formula: see text]m in
      aerodynamic diameter (PM[Formula: see text]). We find positive associations
      between PM[Formula: see text] exposure during early and mid-pregnancy, and
      evidence that associations are stronger for PTBs occurring around week 30. 

PMID- 25573001
TI  - Cost-effectiveness analysis of the Xpert MTB/RIF assay for rapid diagnosis of
      suspected tuberculosis in an intermediate burden area.
AB  - OBJECTIVES: We examined, from a Hong Kong healthcare providers' perspective, the
      cost-effectiveness of rapid diagnosis with Xpert in patients hospitalized for
      suspected active pulmonary tuberculosis (PTB). METHODS: A decision tree was
      designed to simulate outcomes of three diagnostic assessment strategies in adult
      patients hospitalized for suspected active PTB: conventional approach, sputum
      smear plus Xpert for acid-fast bacilli (AFB) smear-negative, and a single sputum
      Xpert test. Model inputs were derived from the literature. Outcome measures were
      direct medical cost, one-year mortality rate, quality-adjusted life-years (QALYs)
      and incremental cost per QALY (ICER). RESULTS: In the base-case analysis, Xpert
      was more effective with higher QALYs gained and a lower mortality rate when
      compared with smear plus Xpert by an ICER of USD99. A conventional diagnostic
      approach was the least preferred option with the highest cost, lowest QALYs
      gained and highest mortality rate. Sensitivity analysis showed that Xpert would
      be the most cost-effective option if the sensitivity of sputum AFB smear
      microscopy was <=74%. The probabilities of Xpert, smear plus Xpert and a
      conventional approach to be cost-effective were 94.5%, 5.5% and 0%, respectively,
      in 10,000 Monte Carlo simulations. CONCLUSIONS: The Xpert sputum test appears to
      be a highly cost-effective diagnostic strategy for patients with suspected active
      PTB in an intermediate burden area like Hong Kong.

PMID- 25573002
TI  - Simulation of bright-field microscopy images depicting pap-smear specimen.
AB  - As digital imaging is becoming a fundamental part of medical and biomedical
      research, the demand for computer-based evaluation using advanced image analysis
      is becoming an integral part of many research projects. A common problem when
      developing new image analysis algorithms is the need of large datasets with
      ground truth on which the algorithms can be tested and optimized. Generating such
      datasets is often tedious and introduces subjectivity and interindividual and
      intraindividual variations. An alternative to manually created ground-truth data
      is to generate synthetic images where the ground truth is known. The challenge
      then is to make the images sufficiently similar to the real ones to be useful in
      algorithm development. One of the first and most widely studied medical image
      analysis tasks is to automate screening for cervical cancer through Pap-smear
      analysis. As part of an effort to develop a new generation cervical cancer
      screening system, we have developed a framework for the creation of realistic
      synthetic bright-field microscopy images that can be used for algorithm
      development and benchmarking. The resulting framework has been assessed through a
      visual evaluation by experts with extensive experience of Pap-smear images. The
      results show that images produced using our described methods are realistic
      enough to be mistaken for real microscopy images. The developed simulation
      framework is very flexible and can be modified to mimic many other types of
      bright-field microscopy images.

PMID- 25573003
TI  - Synergy in activating class I PI3Ks.
AB  - The class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that transduce a
      host of cellular signals and regulate a broad range of essential functions
      including growth, proliferation, and migration. As such, PI3Ks have pivotal roles
      in diseases such as cancer, diabetes, primary immune disorders, and inflammation.
      These enzymes are activated downstream of numerous activating stimuli including
      receptor tyrosine kinases, G protein-coupled receptors (GPCRs), and the Ras
      superfamily of small G proteins. A major challenge is to decipher how each PI3K
      isoform is able to successfully synergize these inputs into their intended
      signaling function. This article highlights recent progress in characterizing the
      molecular mechanisms of PI3K isoform-specific activation pathways, as well as
      novel roles for PI3Ks in human diseases, specifically cancer and immune diseases.

PMID- 25573004
TI  - An evolutionary biochemist's perspective on promiscuity.
AB  - Evolutionary biochemists define enzyme promiscuity as the ability to catalyze
      secondary reactions that are physiologically irrelevant, either because they are
      too inefficient to affect fitness or because the enzyme never encounters the
      substrate. Promiscuous activities are common because evolution of a perfectly
      specific active site is both difficult and unnecessary; natural selection ceases
      when the performance of a protein is 'good enough' that it no longer affects
      fitness. Although promiscuous functions are accidental and physiologically
      irrelevant, they are of great importance because they provide opportunities for
      the evolution of new functions in nature and in the laboratory, as well as
      targets for therapeutic drugs and tools for a wide range of technological
      applications. 

PMID- 25573006
TI  - Global ratings of change do not accurately reflect functional change over time in
      clinical practice.
AB  - STUDY DESIGN: Retrospective longitudinal cohort study. OBJECTIVES: To determine
      whether the global rating of change (GROC) is valid for assessing functional
      change over time in the clinical setting, and whether validity decreases as
      length of recall increases. BACKGROUND: The validity of GROC instruments for
      representing change over time has been questioned. Our previous study showed that
      GROC did not adequately represent functional change over time in patients with
      knee disorders. This was a validation study in patients with hip or ankle/foot
      disorders. METHODS: We obtained complete data from the Focus On Therapeutic
      Outcomes clinical database on episodes of care for 7341 patients with hip or
      ankle/foot disorders. Functional status (FS) was assessed at the intake and
      discharge physical therapy visits via computerized adaptive testing. Each
      patient's GROC was assessed at the discharge visit. We assessed the extent to
      which GROC was associated with intake, discharge, and change in FS using
      correlation and linear regression analyses, stratified by recall period and
      anatomical location. RESULTS: Correlations of GROC with hip and ankle FS change
      scores were modest for recall less than 30 days and deteriorated further as the
      recall period lengthened. Prediction of GROC from discharge and change in FS
      scores by linear regression modeling demonstrated a decline of standardized beta
      coefficients and R2 values as the recall period lengthened. Regression analyses
      indicated that GROC was biased toward discharge FS, with little or no influence
      of intake FS. CONCLUSION: These results confirm that GROC does not adequately or
      consistently correlate with functional change across varying lengths of time, and
      is therefore not recommended as a substitute for change scores on valid
      functional outcome measures for use in routine clinical practice.

PMID- 25573007
TI  - Baseline pain intensity is a predictor of chronic pain in individuals with distal
      radius fracture.
AB  - STUDY DESIGN: Secondary analysis of cohort study. OBJECTIVE: This study examined
      whether baseline pain intensity is a predictor of chronic pain and wrist/hand
      functions at 1 year following distal radius fracture (DRF). The study also
      examined the cutoff level for baseline pain intensity that best predicted chronic
      pain. BACKGROUND: Many individuals experience wrist/hand pain and functional
      impairments for as long as 1 year after DRF. Early identification of individuals
      at risk of these adverse outcomes can facilitate the delivery of required
      interventions to mitigate the risk. METHODS: Data for the Patient-Rated Wrist
      Evaluation (PRWE) pain and function subscales at baseline and 1 year after DRF,
      age, sex, injury to the dominant side, presence of comorbidity, education level,
      mechanism of fracture, smoking status, fall history, and energy of fracture were
      extracted from an existing data set. Multivariate regression analysis examined
      the utility of baseline pain intensity and the above variables in predicting pain
      and functional status at 1 year in individuals with DRF. Receiver operating
      characteristic curves examined the sensitivity/specificity of baseline pain
      intensity in predicting chronic pain and functional impairment. RESULTS: Required
      data were available for 386 individuals. Baseline pain intensity was found to be
      a strong predictor of chronic pain, explaining 22% of the variance. A baseline
      score of 35 out of 50 on the pain subscale of the PRWE had the best sensitivity
      (85%) and specificity (79%) cutoff values for predicting chronic pain at 1 year
      after DRF. CONCLUSION: Rehabilitation practitioners may be able to use a score of
      greater than 35/50 on the PRWE pain subscale to screen individuals at risk of
      chronic pain following DRF. LEVEL OF EVIDENCE: Prognosis, level 4.

PMID- 25573008
TI  - Measurement properties of the Brazilian version of the Penn Shoulder Score (PSS
      Brazil): reliability, validity, and responsiveness.
AB  - STUDY DESIGN: Clinical measurement. OBJECTIVES: To determine the reliability,
      validity, and responsiveness of the Brazilian version of the Penn Shoulder Score
      (PSS-Brazil) in patients with shoulder dysfunctions. BACKGROUND: Several
      questionnaires assessing shoulder dysfunctions are available in Brazil, but the
      measurement properties of most of them, such as the PSS, have not yet been
      tested. METHODS: Internal consistency, measurement error, construct validity, and
      floor and ceiling effects were evaluated in 62 patients, 36 of whom completed the
      questionnaire at baseline and after 2 to 7 days to assess test-retest
      reliability. Responsiveness was determined with 50 patients who completed the
      questionnaire at an initial visit and after 4 weeks of physical therapy. RESULTS:
      The PSS-Brazil displayed acceptable internal consistency, with a Cronbach alpha
      of .92. Test-retest reliability was excellent, with an intraclass correlation
      coefficient of 0.95; the standard error of measurement and minimal detectable
      change were 12.8 and 14.4 points, respectively. A high correlation was obtained
      between the PSS and the Shoulder Pain and Disability Index (0.96) and the
      Disabilities of the Arm, Shoulder and Hand questionnaire (0.86). There was
      moderate correlation between the PSS and its subscales and the pain and function
      subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey (0.40
      0.68). There was high responsiveness, with an effect size of 0.95 and
      standardized response mean of 1.13 for patients with improvement of shoulder
      dysfunction, and adequate area under the curve of 0.81. No floor or ceiling
      effects were observed. CONCLUSION: The PSS-Brazil is a reliable, valid, and
      responsive measure for assessing patients with shoulder dysfunction.

PMID- 25573009
TI  - Diagnostic clinical prediction rules for specific subtypes of low back pain: a
      systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: To identify diagnostic clinical
      prediction rules (CPRs) for low back pain (LBP) and to assess their readiness for
      clinical application. BACKGROUND: Significant research has been invested into the
      development of CPRs that may assist in the meaningful subgrouping of patients
      with LBP. To date, very little is known about diagnostic forms of CPRs for LBP,
      which relate to the present status or classification of an individual, and
      whether they have been developed sufficiently to enable their application in
      clinical practice. METHODS: A sensitive electronic search strategy using 7
      databases was combined with hand searching and citation tracking to identify
      eligible studies. Two independent reviewers identified relevant studies for
      inclusion using a 2-stage selection process. The quality appraisal of included
      studies was conducted by 2 independent raters using the Quality Assessment of
      Diagnostic Accuracy Studies-2 and checklists composed of accepted methodological
      standards for the development of CPRs. RESULTS: Of 10 014 studies screened for
      eligibility, the search identified that 13 diagnostic CPRs for LBP have been
      derived. Among those, 1 tool for identifying lumbar spinal stenosis and 2 tools
      for identifying inflammatory back pain have undergone validation. No impact
      analysis studies were identified. CONCLUSION: Most diagnostic CPRs for LBP are in
      their initial development phase and cannot be recommended for use in clinical
      practice at this time. Validation and impact analysis of the diagnostic CPRs
      identified in this review are warranted, particularly for those tools that meet
      an identified unmet need of clinicians who manage patients with LBP. LEVEL OF
      EVIDENCE: Diagnosis, level 2a-.

PMID- 25573010
TI  - Differences in health-related quality of life among subjects with frequent
      bilateral or unilateral knee pain: data from the Osteoarthritis Initiative study.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To examine associations between
      frequent bilateral knee pain (BKP) and unilateral knee pain (UKP) and health
      related quality of life (QoL). We hypothesized that frequent BKP would be
      associated with poorer health-related QoL than would frequent UKP and no knee
      pain. BACKGROUND: Knee pain is one of the most frequently reported types of joint
      pain among adults in the United States. It is the most frequent cause of limited
      physical function, disability, and reduced QoL. METHODS: Data were collected from
      the Osteoarthritis Initiative public-use data sets. Health-related QoL was
      assessed in 2481 participants (aged 45-79 years at baseline). The Knee injury and
      Osteoarthritis Outcome Score QoL subscale (knee-specific measure) and the
      physical component summary and mental component summary (MCS) scores of the
      Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) (generic measure)
      were used to assess health-related QoL. Multiple regression analyses were used to
      examine the relationships between frequent knee pain and health-related QoL,
      adjusted for sociodemographic and health covariates. RESULTS: Compared with
      subjects with no knee pain, subjects with frequent BKP and UKP had significantly
      lower scores on the Knee injury and Osteoarthritis Outcome Score QoL subscale
      (mean difference, -35.2; standard error [SE], 0.86; P<.001 and mean difference, 
      29.2; SE, 0.93; P<.001; respectively) and the SF-12 physical component summary
      score (mean difference, -6.25; SE, 0.41; P<.001 and mean difference, -4.10; SE,
      0.43; P<.001; respectively), after controlling for sociodemographic and health
      covariates. The SF-12 MCS score was lower among those with BKP (-1.29; SE, 0.42;
      P<.001). Frequent UKP was not associated with the SF-12 MCS. CONCLUSION: Subjects
      with frequent BKP had lower health-related QoL than those with frequent
      unilateral or no knee pain, as reflected in lower Knee injury and Osteoarthritis
      Outcome Score QoL subscale and SF-12 physical component summary and MCS scores.

PMID- 25573012
TI  - Corrigendum.

PMID- 25573005
TI  - Nutrition, dietary interventions and prostate cancer: the latest evidence.
AB  - Prostate cancer (PCa) remains a leading cause of mortality in US men and the
      prevalence continues to rise world-wide especially in countries where men consume
      a 'Western-style' diet. Epidemiologic, preclinical and clinical studies suggest a
      potential role for dietary intake on the incidence and progression of PCa. 'This
      minireview provides an overview of recent published literature with regard to
      nutrients, dietary factors, dietary patterns and PCa incidence and progression.
      Low carbohydrates intake, soy protein, omega-3 (w-3) fat, green teas, tomatoes
      and tomato products and zyflamend showed promise in reducing PCa risk or
      progression. A higher saturated fat intake and a higher beta-carotene status may
      increase risk. A 'U' shape relationship may exist between folate, vitamin C,
      vitamin D and calcium with PCa risk. Despite the inconsistent and inconclusive
      findings, the potential for a role of dietary intake for the prevention and
      treatment of PCa is promising. The combination of all the beneficial factors for
      PCa risk reduction in a healthy dietary pattern may be the best dietary advice.
      This pattern includes rich fruits and vegetables, reduced refined carbohydrates,
      total and saturated fats, and reduced cooked meats. Further carefully designed
      prospective trials are warranted. 

PMID- 25573011
TI  - Drosophila oocytes as a model for understanding meiosis: an educational primer to
      accompany "corolla is a novel protein that contributes to the architecture of the
      synaptonemal complex of Drosophila".
AB  - Achieving a thorough understanding of the events and ramifications of meiosis is
      a common learning objective for undergraduate introductory biology, genetics, and
      cell biology courses. Meiosis is also one of the most challenging cellular
      processes for students to conceptualize. Connecting textbook descriptions of
      meiosis to current research in the field of genetics in a problem-based learning
      format may aid students' understanding of this important biological concept. This
      primer seeks to assist students and instructors by providing an introductory
      framework upon which to integrate discussions of current meiosis research into
      traditional genetics or cell biology curriculum.

PMID- 25573015
TI  - [Diagnosis and treatment of well differentiated thyroid cancer analysis and
      National Comprehensive Cancer Network guideline practice].

PMID- 25573018
TI  - Clients' experiences of formulation in cognitive behaviour therapy.
AB  - OBJECTIVES: To explore clients' experiences of formulation in cognitive behaviour
      therapy for depression and/or anxiety, as reported after the end of therapy.
      DESIGN: A qualitative study using inductive thematic analysis. METHOD: Ten
      clients who had completed a course of cognitive behaviour therapy for depression
      and/or anxiety participated in semi-structured interviews within a month of
      finishing therapy. RESULTS: Four overarching themes were identified: Formulation
      helps me to understand my problems; formulation leads to feeling understood and
      accepted; formulation leads to an emotional shift and formulation enables me to
      move forward. CONCLUSIONS: Formulation is a powerful therapeutic tool that can be
      highly beneficial to clients, leading to an increased understanding of their
      difficulties, feeling understood and accepted and a sense of relief. The process
      of formulation can also result in distress, however, when associated with an
      increased awareness of the nature of one's difficulties, the implications of the
      formulation for one's sense of identity and being presented with a formulation
      that is perceived to be inaccurate. In some cases, this distress decreased during
      therapy, while for others, distress lasted beyond the end of therapy. Formulation
      enabled many participants to move forwards from their difficulties, leading them
      to feel empowered, helping them to cope, enabling them to talk more openly, in
      contrast to previous therapy which had not focused on formulation. Clinical
      implications indicate that formulation should be undertaken in a sensitive and
      collaborative way to maximize its benefits and minimize any possible negative
      effects. PRACTITIONER POINTS: Formulation can be highly beneficial for clients
      enabling them to move forwards from their difficulties. It is important to be
      mindful of clients' possible adverse reactions to the formulation, so that these
      can be resolved during therapy. Formulation should be undertaken attentively
      sensitively and collaboratively to maximize its benefits and minimize negative
      effects.

PMID- 25573017
TI  - The Mental Disability Military Assessment Tool: A Reliable Tool for Determining
      Disability in Veterans with Post-traumatic Stress Disorder.
AB  - PURPOSE: An assessment tool was developed to assess disability in veterans who
      suffer from post-traumatic stress disorder (PTSD) due to a military mission. The
      objective of this study was to determine the reliability, intra-rater and inter
      rater variation of the Mental Disability Military (MDM) assessment tool. METHODS:
      Twenty-four assessment interviews of veterans with an insurance physician were
      videotaped. Each videotaped interview was assessed by a group of five independent
      raters on limitations of the veterans using the MDM assessment tool. After 2
      months the raters repeated this procedure. Next the intra-rater and inter-rater
      variation was assessed with an adjusted version of AG09 computing weighted
      percentage agreement. RESULTS: The results of this study showed that both the
      intra-rater variation and inter-rater variation on the ten subcategories of the
      MDM assessment tool were small, with an agreement of 84-100% within raters and 93
      100% between raters. CONCLUSIONS: The MDM assessment tool proves to be a reliable
      instrument to measure PTSD limitations in functioning in Dutch military veterans
      who apply for disability compensation. Further research is needed to assess the
      validity of this instrument.

PMID- 25573019
TI  - Factors influencing community pharmacists' likelihood to ask medication
      monitoring questions: A factorial survey.
AB  - BACKGROUND: Community pharmacists are well positioned to identify and resolve
      medication related problems associated with chronic medication use during
      prescription dispensing, a process referred to as medication monitoring.
      Pharmacists need feedback about patient medication experiences to engage in
      effective monitoring, but the pharmacist's decision making process for when to
      ask questions to solicit this information from patients has not been established.
      OBJECTIVES: Identify significant factors contributing to a community pharmacist's
      likelihood to ask medication monitoring questions at the time of refill. METHODS:
      A factorial survey approach was used to test the effect of several pharmacist,
      patient, environment, drug, and past interaction factors (the domains of the
      Health Collaboration Model) on a pharmacist's self-reported likelihood to ask non
      adherence, side effect, and effectiveness monitoring questions for 5 randomly
      populated refill prescription dispensing vignettes. Surveys containing the
      vignettes, demographic items, and a new medication monitoring attitude measure
      were mailed to 599 community pharmacists. Hierarchical linear regression was used
      to test the independent effects of the vignette and pharmacist factors. RESULTS:
      There were 254 (42.4%) returned and usable surveys. The hierarchical linear
      regression models showed that adherence questioning was driven more by the
      vignette characteristics whereas side effect and effectiveness questioning were
      more driven by the pharmacist. Overall, warfarin and hydrocodone were seen as
      more question-worthy than fluoxetine or metoprolol. The number of additional
      persons waiting in the pharmacy decreased, and more days late increased the
      likelihood of asking the three monitoring questions. An exception was hydrocodone
      where early fills prompted question asking. For side effect and effectiveness
      questioning, being short-staffed and the prescription previously being filled
      more times decreased question asking likelihood. DISCUSSION: Factorial surveys
      are a useful approach to independently measuring the impact of respondent and
      contextual variables on pharmacist judgments. Reactions to the vignettes
      demonstrated that multiple factors go into a pharmacist's mental model when
      deciding to ask a question at the time of refill. The lateness of a refill
      prescription was a significant cue to question asking. Pharmacies can ensure late
      refill information is reaching pharmacists as a means to increase in medication
      monitoring. Pharmacies also can design work environments and workflows conducive
      to question asking and prompt pharmacists to address potentially under-discussed
      medications.

PMID- 25573020
TI  - Development and assessment of a new 3D neuroanatomy teaching tool for MRI
      training.
AB  - A computerized three-dimensional (3D) neuroanatomy teaching tool was developed
      for training medical students to identify subcortical structures on a magnetic
      resonance imaging (MRI) series of the human brain. This program allows the user
      to transition rapidly between two-dimensional (2D) MRI slices, 3D object
      composites, and a combined model in which 3D objects are overlaid onto the 2D MRI
      slices, all while rotating the brain in any direction and advancing through
      coronal, sagittal, or axial planes. The efficacy of this tool was assessed by
      comparing scores from an MRI identification quiz and survey in two groups of
      first-year medical students. The first group was taught using this new 3D
      teaching tool, and the second group was taught the same content for the same
      amount of time but with traditional methods, including 2D images of brain MRI
      slices and 3D models from widely used textbooks and online sources. Students from
      the experimental group performed marginally better than the control group on
      overall test score (P = 0.07) and significantly better on test scores extracted
      from questions involving C-shaped internal brain structures (P < 0.01).
      Experimental participants also expressed higher confidence in their abilities to
      visualize the 3D structure of the brain (P = 0.02) after using this tool.
      Furthermore, when surveyed, 100% of the students in the experimental group
      recommended this tool for future students. These results suggest that this
      neuroanatomy teaching tool is an effective way to train medical students to read
      an MRI of the brain and is particularly effective for teaching C-shaped internal
      brain structures.

PMID- 25573021
TI  - Evaluation of combined argon plasma coagulation and Savary Bougienage for the
      relief of anastomotic-stenosis after esophageal squamous cancer surgery.
AB  - BACKGROUND: Several endoscopic dilation techniques have been reported for
      treatment of anastomotic-stenosis of esophageal cancer, but the high incidence of
      dysphagia has remained unchanged. The aim of this study was to compare the effect
      of Argon Plasma Coagulation (APC) combined with Savary Bougienage (SB) compared
      to APC alone or SB alone for anastomotic-stenosis after radical operation for
      squamous cell carcinoma of the esophagus. METHODS: Patients with anastomotic
      stenosis that was diagnosed for the first time following esophageal squamous cell
      carcinoma resection surgery were randomly assigned to undergo APC combined with
      SB, APC alone, or SB alone. Primary endpoints were the dysphagia-free survival
      (DFS defined as the time from first dilatation of effectively relieved dysphagia
      to dysphagia relapse expressed in days) after 6 months of follow up. RESULTS: A
      total of 90 patients from the Cancer Institute, First Affiliated Hospital of
      Henan University of Science and Technology were entered into the study (APC
      group, n = 30, SB group, n = 30, combination group [APC combined with SB], n =
      30). Primary endpoints: 6 months after treatment, DFS of combination group
      (115.63 days; 95% CI, 105.31-125.95) was significantly longer than the APC alone
      group (39.53 days; 95% CI, 35.95-43.11, p = 0.000) and the SB alone group (16.93
      days; 95% CI, 15.01-18.84, p = 0.000). No severe complications occurred within
      the three treatment groups. CONCLUSIONS: APC combined with SB was a safe and well
      tolerated method for relieving dysphagia of esophageal squamous cell cancer
      patients with anastomotic-stenosis. (Registered with randomized controlled
      trials, ChiCRT, registration number ChiCTR-TRC-13003757.)

PMID- 25573022
TI  - Improving outcomes for late preterm infants and their mothers.

PMID- 25573023
TI  - A preclinical model of hyperalgesia following spinal stenosis/compression.
AB  - BACKGROUND: Identification of mechanisms for pain/hyperalgesia following spinal
      cord injury requires long-term evaluation of individual subjects because of the
      variability in effect over time for humans. METHODS: Rats were trained on an
      operant escape task that determined their preference for occupancy of a brightly
      lit compartment versus a dark compartment with a floor preheated to 10, 32 or
      44.5  degrees C. Following determination of baseline preferences, the animals
      received extradural implantation of a small piece of polymer in the thoracic
      spinal canal. The polymer narrowed the spinal canal and compressed the spinal
      cord. Post-operative tests of escape preference were conducted over 23 weeks
      (experiments 1 and 2) and 62 weeks (experiment 3), permitting statistical
      evaluation of individual effects. RESULTS: Spinal stenosis/compression produced
      hyperalgesia for cold and/or heat stimulation (17 animals; 77%), no post
      operative change in sensitivity (4 animals) or hypoalgesia for cold or heat (2
      animals). When hyperalgesia occurred, it developed gradually over 4 months.
      Following removal of the polymer in experiment 3, heat sensitivity returned to
      baseline levels for four of four animals that had been hyperalgesic when the
      polymer was in place, but cold hyperalgesia was retained for four of five
      animals. Overall, post-operative changes in cold and heat sensitivity were not
      strongly related, indicating that different mechanisms were responsible for
      enhanced sensitivity to 10 and 44.5  degrees C. CONCLUSIONS: Histology revealed
      that hyperalgesia occurred when there was: (1) damage to spinal white matter; or
      (2) cystic cavitation; or (3) compression and distortion of the spinal cord
      without an obvious loss of grey or white matter.

PMID- 25573026
TI  - Hyperbranched crystalline nanostructure produced from ionic pi-conjugated
      molecules.
AB  - Self-assembled crystalline nanostructures with sheaf-like morphology fabricated
      from tetra(4-aminophenyl)porphyrin and tetra(4-sulfonatophenyl)porphyrin are
      reported for the first time. The hierarchical sheaf-like growth of the assemblies
      exhibits Arrhenius behaviour. The observed morphology results from crystal
      splitting during initial oriented attachment growth followed by Ostwald ripening.

PMID- 25573025
TI  - Repetitive transcranial magnetic stimulation; A cost-effective and beneficial
      treatment option for refractory focal seizures.

PMID- 25573024
TI  - Systems biology with high-throughput sequencing reveals genetic mechanisms
      underlying the metabolic syndrome in the Lyon hypertensive rat.
AB  - BACKGROUND: The metabolic syndrome (MetS) is a collection of co-occurring complex
      disorders including obesity, hypertension, dyslipidemia, and insulin resistance.
      The Lyon hypertensive and Lyon normotensive rats are models of MetS sensitivity
      and resistance, respectively. To identify genetic determinants and mechanisms
      underlying MetS, an F2 intercross between Lyon hypertensive and Lyon normotensive
      was comprehensively studied. METHODS AND RESULTS: Multidimensional data were
      obtained including genotypes of 1536 single-nucleotide polymorphisms, 23
      physiological traits, and >150 billion nucleotides of RNA-seq reads from the
      livers of F2 intercross offspring and parental rats. Phenotypic and expression
      quantitative trait loci (eQTL) were mapped. Application of systems biology
      methods identified 17 candidate MetS genes. Several putative causal cis-eQTL were
      identified corresponding with phenotypic QTL loci. We found an eQTL hotspot on
      rat chromosome 17 that is causally associated with multiple MetS-related traits
      and found RGD1562963, a gene regulated in cis by this eQTL hotspot, as the most
      likely eQTL driver gene directly affected by genetic variation between Lyon
      hypertensive and Lyon normotensive rats. CONCLUSIONS: Our study sheds light on
      the intricate pathogenesis of MetS and demonstrates that systems biology with
      high-throughput sequencing is a powerful method to study the pathogenesis of
      complex genetic diseases.

PMID- 25573027
TI  - A randomized controlled study of neuromuscular electrical stimulation in
      oropharyngeal dysphagia secondary to acquired brain injury.
AB  - BACKGROUND AND PURPOSE: To evaluate the effectiveness of neuromuscular electrical
      stimulation (NMES) treatment in patients with oropharyngeal dysphagia secondary
      to acquired brain injury. METHODS: Twenty patients with neurological
      oropharyngeal dysphagia (14 stroke and six severe traumatic brain injury) were
      enrolled in a prospective randomized study, with patients and assessors blinded
      (to group allocation): 10 patients underwent NMES and conventional swallowing
      therapy and 10 patients underwent sham electrical stimulation (SES) and
      conventional swallowing therapy. Both groups completed 20 sessions. At baseline,
      at the end of treatment (1 month) and at 3-month follow-up, clinical,
      videofluoroscopic and esophageal manometric analyses were done. Feeding
      swallowing capacity was evaluated using the functional oral intake scale (FOIS).
      RESULTS: Mean FOIS score before treatment was 1.9 for the NMES group and 2.1 for
      the SES group. After treatment, the NMES group increased by 2.6 points (4.5
      points) compared with only 1 point (3.1 points) for the SES group (P = 0.005). At
      3 months of follow-up, mean scores were 5.3 and 4.6 respectively; thus, both
      groups improved similarly. At that time point (3 months), tracheal aspiration
      persisted in six patients in each group. However, a significant improvement in
      relation to the bolus viscosity at which aspiration appeared was found in the
      NMES group versus the SES group (P = 0.015). Also, a significant increase (P =
      0.04) in pharyngeal amplitude contraction was observed at the end of treatment (1
      month) in the NMES group compared with the SES group. CONCLUSION: Neuromuscular
      electrical stimulation significantly accelerated swallowing function improvement
      in patients with oropharyngeal dysphagia secondary to acquired brain injury.

PMID- 25573028
TI  - Comment on the paper by Douvali et al. entitled 'effect of macular ischemia on
      intravitreal ranibizumab treatment for diabetic macular edema'.

PMID- 25573029
TI  - RNA-sequencing analysis of Trichophyton rubrum transcriptome in response to
      sublethal doses of acriflavine.
AB  - BACKGROUND: The dermatophyte Trichophyton rubrum is an anthropophilic filamentous
      fungus that infects keratinized tissues and is the most common etiologic agent
      isolated in human dermatophytoses. The clinical treatment of these infections is
      challenging because only few antifungal drugs are commercially available. To
      understand the mode of action of cytotoxic drugs against fungi, we evaluated the
      time-dependent effects of acriflavine on T. rubrum transcriptome using high
      throughput RNA-sequencing (RNA-seq) technology. RESULTS: RNA-seq analysis
      generated approximately 200 million short reads that were mapped to the Broad
      Institute's Dermatophyte Comparative Database before differential gene expression
      analysis was performed. By employing a stringent cut-off threshold of -1.5 and
      1.5 log2-fold changes in gene expression, a subset of 490 unique genes were found
      to be modulated in T. rubrum in response to acriflavine exposure. Among the
      selected genes, 69 genes were modulated at all exposure time points. Functional
      categorization indicated the putative involvement of these genes in various
      cellular processes such as oxidation-reduction reaction, transmembrane transport,
      and metal ion binding. Interestingly, genes putatively involved in the
      pathogenicity of dermatophytoses were down-regulated suggesting that this drug
      interferes with the virulence of T. rubrum. Moreover, we identified 159 novel
      putative transcripts in intergenic regions and two transcripts in intron regions
      of T. rubrum genome. CONCLUSION: The results provide insights into the molecular
      events underlying the stress responses of T. rubrum to acriflavine, revealing
      that this drug interfered with important molecular events involved in the
      establishment and maintenance of fungal infection in the host. In addition, the
      identification of novel transcripts will further enable the improvement of gene
      annotation and open reading frame prediction of T. rubrum and other dermatophyte
      genomes.

PMID- 25573031
TI  - Diffusion model to describe osteogenesis within a porous titanium scaffold.
AB  - In this study, we develop a two-dimensional finite element model, which is
      derived from an animal experiment and allows simulating osteogenesis within a
      porous titanium scaffold implanted in ewe's hemi-mandible during 12 weeks. The
      cell activity is described through diffusion equations and regulated by the
      stress state of the structure. We compare our model to (i) histological
      observations and (ii) experimental data obtained from a mechanical test done on
      sacrificed animal. We show that our mechano-biological approach provides
      consistent numerical results and constitutes a useful tool to predict
      osteogenesis pattern.

PMID- 25573030
TI  - Liraglutide inhibits autophagy and apoptosis induced by high glucose through GLP
      1R in renal tubular epithelial cells.
AB  - Tubular atrophy and dysfunction is a critical process underlying diabetic
      nephropathy (DN). Understanding the mechanisms underlying renal tubular
      epithelial cell survival is important for the prevention of kidney failure
      associated with glucotoxicity. Autophagy is a cellular pathway involved in
      protein and organelle degradation. It is associated with many types of cellular
      homeostasis and human diseases. To date, little is known of the association
      between high concentrations of glucose and autophagy in renal tubular cells. In
      the present study, we investigated high glucose-induced toxicity in renal tubular
      epithelial cells by means of several complementary assays, including cell
      viability, cell death assays and changes in ultrastructure in an immortalized
      human kidney cell line, HK-2 cells. The extent of apoptosis was significantly
      increased in the HK-2 cells following treatment with high levels of glucose. In
      addition, in in vivo experiments using diabetic rats, high glucose exerted
      harmful effects on the tissue structure of the kidneys in the diabetic rats.
      Chronic exposure of the HK-2 cells and tubular epithelial cells of nephritic rats
      to high levels of glucose induced autophagy. Liraglutide inhibited these effects;
      however, treatment witht a glucagon-like peptide-1 receptor (GLP-1R) antagonist
      enhanced these effects. Our results also indicated that the exposure of the renal
      tubular epithelial cells to high glucose concentrations in vitro led to the
      downregulation of GLP-1R expression. Liraglutide reversed this effect, while the
      GLP-1R antagonist promoted it, promoting autophagy, suggesting that liraglutide
      exerts a renoprotective effect in the presence of high glucose, at least in part,
      by inhibiting autophagy and increasing GLP-1R expression in the HK-2 cells and
      kidneys of diabetic rats.

PMID- 25573032
TI  - Reply to Letter: confirmation of the depth of the endotracheal tube: where should
      the cuff be?

PMID- 25573033
TI  - Managing children with chronic myeloid leukaemia--response to Baccarani.

PMID- 25573034
TI  - Regulatory considerations in the clinical development of vaccines indicated for
      use during pregnancy.
AB  - Despite supportive public health policies (e.g., ACIP recommendations), the
      potential for providing clinical benefit through maternal immunization has yet to
      be fully realized. For vaccines already licensed and approved for use in adults,
      specific FDA approval for use during pregnancy to prevent disease in the mother
      and/or infant may have a significant impact on uptake and usage in pregnant
      women. In addition, for either a licensed vaccine or a novel vaccine, FDA
      approval for use during pregnancy would result in labeling that would serve as a
      resource for practitioners and would facilitate the safe and effective use of the
      vaccine during pregnancy. In the U.S., while many vaccines are approved for use
      in adults and most are not contraindicated for use in pregnant women, no vaccine
      is licensed for use specifically during pregnancy. Among the perceived obstacles
      hindering the clinical development of vaccines for use in pregnancy, regulatory
      issues are frequently cited. One aim of this article is to address the perceived
      regulatory obstacles. General concepts and regulatory considerations for clinical
      safety and effectiveness evaluations for vaccines indicated for use during
      pregnancy will be discussed. This discussion is not intended to establish data
      requirements or to articulate agency policy or guidance regarding specific
      vaccine products. 

PMID- 25573035
TI  - Combined tetanus-diphtheria and pertussis vaccine during pregnancy: transfer of
      maternal pertussis antibodies to the newborn.
AB  - BACKGROUND AND OBJECTIVES: Pertussis is currently an emerging public health
      concern in some countries with high vaccination coverage. It is expected that
      maternal pertussis immunization could provide newborn protection. We compared
      pertussis toxin antibody (anti-PT) levels in women during pregnancy (pre- and
      post-vaccination) with respect to levels in the newborn at delivery in women
      vaccinated during pregnancy. We also estimated anti-PT titers at primary infant
      vaccination. METHODS: Observational study of pregnant women vaccinated with Tdap
      (>=20 weeks gestation) and their newborns between May 2012 and August 2013. Anti
      PT levels were determined by ELISA in maternal (pre- and post-vaccination) and
      newborn blood. RESULTS: Pre-vaccination, post-vaccination maternal and newborn
      samples were available in 132 subjects. Mean maternal age was 34.2 (SD 4.3)
      years. Median weeks of gestation at vaccination were 27.2 (Q1-Q3 21.7-30.8). Anti
      PT (>=10 IU/ml) levels were found in 37.1% of maternal pre-vaccination samples
      (geometric mean titer (GMT) 7.9 IU/ml (95% CI 6.8-9.2)), 90.2% of post
      vaccination samples (GMT 31.1 IU/ml (95% CI 26.6-36.3)) and 94.7% of newborns
      (GMT 37.8 IU/ml (95% CI 32.3-44.1)). The Lin concordance index between post
      vaccination maternal and newborn samples was 0.8 (95% CI 0.8-0.9). Transplacental
      transfer ratio was 146.6%. At two months of age, 66% of newborns had estimated
      anti-PT levels >=10 IU/ml. CONCLUSIONS: There was a high correlation between anti
      PT levels in mothers and newborns, with higher levels in newborns, which should
      be sufficient to provide protection against pertussis during the first months of
      life. Vaccination of pregnant women seems to be an immunogenic strategy to
      protect newborns until primary infant immunization.

PMID- 25573036
TI  - Increasing cellular immunogenicity to peptide-based vaccine candidates using a
      fluorocarbon antigen delivery system.
AB  - Traditionally, synthetic peptide vaccines for infectious diseases and cancer
      require adjuvants to achieve optimal immunogenicity. Here we describe a novel
      method of peptide modification using a fluorocarbon chain which can substantially
      increase peptide-specific cellular immune responses in the absence of adjuvant.
      We demonstrate that fluorocarbon-modified peptides (fluoropeptides) derived from
      HIV, influenza and hepatitis C virus can significantly increase interferon gamma
      ELISpot responses against cytotoxic and T-helper epitopes compared to unmodified
      peptides or lipopeptides in mice. Increases in both T-helper1 and T-helper2
      cytokines are observed. Fluoropeptides show enhanced ability of the antigen to
      persist at the site of administration and persistence is associated with a
      prolonged and elevated immune response. Additionally we demonstrate that
      fluoropeptides have increased proteolytic resistance thereby potentially
      supporting their increased half-life in vivo. Fluorocarbon-modification of
      peptides provides a valuable tool for increasing cellular immunogenicity of
      vaccines for infectious diseases and cancer without requirement for traditional
      adjuvants. 

PMID- 25573037
TI  - Monophosphoryl lipid A coating of hydroxyethyl starch nanocapsules drastically
      increases uptake and maturation by dendritic cells while minimizing the adjuvant
      dosage.
AB  - Enhancing delivery of antigens to dendritic cells (DCs) is essential for the
      induction of vigorous antigen-specific cellular immune responses. Aim of the
      present study was to evaluate the properties of hydroxyethyl starch nanocapsules
      (HES-NCs) functionalized with anti-CD40, anti-DEC205, interferon-gamma (IFNgamma)
      and/or monophosphoryl lipid A (MPLA) with respect to the overall uptake, the
      released cytokine profile, and the influence on phenotypic maturation of human
      monocyte-derived DCs using flow cytometry, confocal microscopy and enzyme-linked
      immunosorbent assays. NC uptake by DCs was significantly enhanced by
      functionalizing NCs with anti-CD40 or MPLA. With respect to the cytokine profile
      and the maturation status, coating with MPLA evoked a strong Th1-type cytokine
      response and significantly increased CD80 and CD83 expression on DCs, contrasting
      the moderate effects of MPLA in solution. Notably, an at least 20 fold higher
      amount of MPLA in solution was needed compared to the dosage of MPLA attached to
      HES-NCs in order to induce comparable effects, evidencing the intense dose
      sparing potential of particle-bound MPLA. Reducing the amount of the vaccine
      adjuvant MPLA, while maintaining or even surpassing the effects on human DCs,
      reveals the potential of HES-NCs as a promising carrier system for the
      simultaneous delivery of antigen along with compounds promoting a Th1-prone
      cellular immune response. 

PMID- 25573039
TI  - Clinical trials submitted to the JID: place your bet and show us your hand.

PMID- 25573038
TI  - Monitoring the impact of human papillomavirus vaccines on high-grade pre-invasive
      cervical lesions: designing a framework of linked immunization information system
      and cancer registry data in Michigan.
AB  - State immunization and cancer registries contain data that, if linked, could be
      used to monitor the impact of human papillomavirus (HPV) vaccine on cervical
      cancer and precancer. Michigan is uniquely positioned to examine these outcomes
      using two population-based resources: the state-wide cancer registry and
      immunization information system (IIS). We assessed the feasibility of identifying
      females in the IIS who had continuous Michigan residence and linking them to the
      cancer registry. We considered continuous residence necessary for future studies
      of vaccine impact to avoid misclassifying those who may have been immunized while
      residing out-of-state and whose immunization therefore may not have been reported
      in Michigan. We identified females with 1976-1996 birthdates in the IIS and used
      probabilistic linkage software to match them with Michigan birth records. A
      stratified random sample of IIS-birth matches was provided to a commercial
      locator service to identify females with continuous Michigan residence. Cervical
      carcinoma in situ cases diagnosed in 2006 among females aged 10 through 30 years
      were also matched with the birth records; cancer registry-birth matches were
      merged with the IIS-birth matches using the birth record identifier. Overall, 68%
      of the 1274,282 IIS and 61% of the 1358 cancer registry records could be matched
      with birth records. Among the sample of IIS-birth matches, most (86%) were
      continuous residents. Seventy percent or more of cancer registry-birth matches
      merged with IIS-birth matches for cases born after 1984. This is the first effort
      in the U.S. to show that linking records across IIS and cancer registries is
      practical and reasonably efficient. The increasing proportion of matches between
      the registries and live birth file with birth year, and the use of population
      based data, strengthen the utility of this approach. Future steps include use of
      this method to examine incidence of cervical cancer precursors in HPV
      immunization-eligible females. 

PMID- 25573043
TI  - Insight from the air-skin interface.
AB  - The epidermis is a relatively hypoxic tissue, despite being continually exposed
      to air. The role of hypoxia in epidermal differentiation and skin barrier
      function is incompletely understood. In this issue, Wong et al. show that hypoxia
      inducible factors are central to the processes of epidermal differentiation and
      barrier formation, in particular by promoting the expression of the key skin
      barrier protein filaggrin. 

PMID- 25573044
TI  - On the role of the endogenous opioid system in regulating epidermal homeostasis.
AB  - The presence of functional opioid receptors on epidermal keratinocytes, with
      attendant regulation of keratinocyte proliferation and differentiation, indicates
      their novel role in maintaining epidermal homeostasis. Expression of
      proenkephalin precursors and neuropeptide products in the same compartment opens
      an opportunity for studying the role of this endogenous opioid circuitry, with
      its regulators, in modulating epidermal barrier function. 

PMID- 25573045
TI  - Panel sequencing melanomas.
AB  - Sequencing samples of melanoma for targetable mutations has become a standard of
      care for metastatic disease. In this issue, Siroy et al. demonstrate how clinical
      genetic analysis is moving from a single-gene Sanger-sequencing approach to
      targeted next-generation sequencing. They present data on a large cohort of
      patients with advanced melanoma, and their data support previous findings and
      also present novel aspects of melanoma genetics. 

PMID- 25573046
TI  - KIT in melanoma: many shades of gray.
AB  - Activating mutations in KIT have been identified in melanomas of acral and
      mucosal types and in those arising in chronically sun-damaged skin. Until now,
      KIT has been considered an oncogenic driver and a potential therapeutic target.
      However, data presented by Dhal et al. show that in cutaneous melanomas the KIT
      promoter is a target for hypermethylation, leading to its downregulation. Their
      observations suggest that signaling pathways downstream of KIT may have distinct
      and opposing roles in the pathogenesis of melanoma subtypes. This will have
      important implications for the use of KIT inhibitors in treating melanomas. 

PMID- 25573047
TI  - TLR3: a receptor that recognizes cell injury is essential for permeability
      barrier homeostasis following UV irradiation.
AB  - The cutaneous permeability barrier is essential for life and perturbations in
      this barrier are repaired rapidly. After minimal injury to the stratum corneum
      alterations in the calcium concentration in the outer epidermis are the primary
      signal inducing this repair response. In this issue, studies demonstrate that
      Toll-like receptor 3 has an important role in signaling permeability barrier
      repair following injury induced by UVB irradiation. 

PMID- 25573048
TI  - Cells to surgery quiz: February 2015.

PMID- 25573049
TI  - JID VisualDx Quiz: February 2015.

PMID- 25573050
TI  - Assessing the in vivo epidermal barrier in mice: dye penetration assays.

PMID- 25573052
TI  - Teaching for the Transition: the Canadian PGY-1 Neurosurgery 'Rookie Camp'.
AB  - BACKGROUND: Transitioning from medical school to residency is difficult and
      stressful, necessitating innovation in easing this transition. In response, a
      Canadian neurosurgical Rookie Camp was designed and implemented to foster
      acquisition of technical, cognitive and behavioral skills among incoming Canadian
      post graduate year one (PGY-1) neurosurgery residents. METHODS: The inaugural
      Rookie Camp was held in July 2012 in Halifax. The curriculum was developed based
      on a national needs-assessment and consisted of a pre-course manual, 7 case-based
      stations, 4 procedural skills stations and 2 group discussions. The content was
      clinically focused, used a variety of teaching methods, and addressed multiple
      CanMEDS competencies. Evaluation included participant and faculty surveys and a
      pre-course, post-course, and 3-month retention knowledge test. RESULTS: 17 of 23
      PGY-1 Canadian neurosurgical residents participated in the Camp. All agreed the
      course content was relevant for PGY-1 training and the experience prepared them
      for residency. All participants would recommend the course to future
      neurosurgical residents. A statistically significant improvement was observed in
      knowledge related to course content (F(2,32) = 7.572, p<0.002). There were no
      significant differences between post-test and retention-test scores at three
      months. CONCLUSION: The inaugural Canadian Neurosurgery Rookie Camp for PGY-1
      residents was successfully delivered, with engagement from participants, training
      programs, the Canadian Neurosurgical Society, and the Royal College. In addition
      to providing fundamental knowledge, which was shown to be retained, the course
      eased junior residents' transition to residency by fostering camaraderie and
      socialization within the specialty.

PMID- 25573053
TI  - Reappearance of serum hepatitis B viral DNA in patients with hepatitis B surface
      antigen seroclearance.

PMID- 25573051
TI  - Optical and photoacoustic dual-modality imaging guided synergistic
      photodynamic/photothermal therapies.
AB  - Phototherapies such as photodynamic therapy (PDT) and photothermal therapy (PTT),
      due to their specific spatiotemporal selectivity and minimal invasiveness, have
      been widely investigated as alternative treatments of malignant diseases.
      Graphene and its derivatives not only have been used as carriers to deliver
      photosensitizers for PDT, but also as photothermal conversion agents (PTCAs) for
      PTT. Herein, we strategically designed and produced a novel photo-theranostic
      platform based on sinoporphyrin sodium (DVDMS) photosensitizer-loaded PEGylated
      graphene oxide (GO-PEG-DVDMS) for enhanced fluorescence/photoacoustic (PA) dual
      modal imaging and combined PDT and PTT. The GO-PEG carrier drastically improves
      the fluorescence of loaded DVDMS via intramolecular charge transfer.
      Concurrently, DVDMS significantly enhances the near-infrared (NIR) absorption of
      GO for improved PA imaging and PTT. The cancer theranostic capability of the as
      prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. This
      novel theranostics is well suited for fluorescence/PA dual-modal imaging and
      synergistic PDT/PTT. 

PMID- 25573054
TI  - A randomized controlled trial to investigate magnetic resonance imaging-targeted
      biopsy as an alternative diagnostic strategy to transrectal ultrasound-guided
      prostate biopsy in the diagnosis of prostate cancer.

PMID- 25573055
TI  - Murine beta-defensin-2 may regulate the effect of bacillus Calmette-Guerin (BCG)
      in normal mouse bladder.
AB  - PURPOSE: We investigated whether bacillus Calmette-Guerin (BCG)-induced secretion
      of murine beta-defensin-2 (mBD2) and determined whether mBD2 regulated BCG
      effects in the normal mouse bladder. MATERIALS AND METHODS: A total of 140
      C57BL/6 female mice were divided into 28 groups, and the experiment was performed
      over 3 steps. In the first step (20 groups), mice bladders were stimulated with
      different doses of BCG (multiplicity of infection [MOI] 0, 1, 10, 30, and 100)
      and histological analysis was conducted in bladder specimens isolated at
      different times (0, 4, 8, and 24h after instillation) to determine optimal dose
      and time point of BCG internalization and urine mBD2 and cytokine concentration.
      In the second step (4 groups), BCG internalization and urine cytokine levels were
      measured after pretreatment of different recombinant mBD2 (rmBD2) (0, 1, 2.5, and
      5 ng/ml) at optimal dose and time point. In the third step (4 groups), BCG
      internalization and urine cytokine levels were compared between pretreatment
      conditions (control, rmBD2, anti-mBD2 Ab, and rmBD2+anti-mBD2 Ab). Urine was
      collected for estimating mBD2 levels and a multiplex analysis for 9 cytokines.
      Real-time polymerase chain reaction assay was used for estimating the relative
      BCG cell number in mice bladder tissue. RESULTS: Bladder edema was induced by BCG
      (MOI 30 and 100), which progressed to an inflammatory infiltrate composed
      primarily of neutrophils and increased mBD2 secretion at 4 hours after
      instillation. Relative BCG cell number and urinary cytokine levels (interferon
      gamma and interleukins [IL]-2, -4, -6, and -10) response pattern was
      characterized by a peak at 4 hours after instillation followed by rapid decline.
      The levels of interferon-gamma, and IL-1beta, -2, -4, -6, and -10 and relative
      BCG cell numbers decreased in a dose-dependent manner according to pretreatment
      with rmBD2 protein, and the responses were potentiated in the anti-mBD2
      pretreatment group at 4 hours after BCG (MOI 30) instillation. CONCLUSION: The
      present results suggest that the mouse urothelium produces mBD2 in response to
      intravesicular BCG as a defense mechanism against BCG, and blocking mBD2 by an
      anti-mBD2 antibody increased the effectiveness of BCG.

PMID- 25573056
TI  - Contemporary trends in postchemotherapy retroperitoneal lymph node dissection:
      Additional procedures and perioperative complications.
AB  - INTRODUCTION: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND)
      is a mainstay in the treatment of men with metastatic testicular cancer. We
      sought to determine whether trends in the need for additional intraoperative
      procedures and development of perioperative complications have changed over time.
      METHODS: Patients undergoing PC-RPLND from 2003 to 2011 were identified in the
      Indiana University Testis Cancer Database. Trends in the incidence of
      perioperative complications and additional procedures were assessed over time
      using regression tests of trend. Complications were classified according to the
      modified Clavien system. Univariable and multivariable logistic regression was
      used to determine factors associated with undergoing additional procedures.
      RESULTS: After exclusion criteria, 755 patients were included in the final study
      cohort. The incidence of additional procedures at PC-RPLND was 22.1% (167 of
      755). The rate of additional procedures per year ranged from 17% to 30%, with no
      significant trend in any direction (Ptrend = 0.66). After adjusting for
      covariates, preoperative retroperitoneal (RP) mass size, elevated markers, and RP
      pathology remained significantly associated with the odds of an additional
      procedure. RP mass size of>10 cm was the strongest predictor (odds ratio = 7.2,
      95% CI: 2.6-19.5). Overall, the incidence of perioperative complications was 3.7%
      (28 of 755). The rate of perioperative complications per year ranged from 0% to
      7.3% with no significant trend in any direction (Ptrend = 0.06). CONCLUSION: The
      incidence of perioperative complications is low with no significant trend over
      the last decade. A substantial number of patients require additional
      intraoperative procedures during PC-RPLND, which has remained stable at our
      institution over time.

PMID- 25573057
TI  - Histopathologic changes in liver and kidney tissues induced by carbaryl in
      Bufotes variabilis (Anura: Bufonidae).
AB  - The purpose of this work was to investigate for the first time histopathologic
      effects of carbaryl in liver and kidney tissues of Bufotes variabilis. After 96h
      following exposure to carbaryl (low dose: 0.05, medium dose: 0.1 and high dose:
      0.2mg/g), the toads were euthanized and dissected. In liver tissue, vacuolization
      in hepatocytes, necrosis, mononuclear cell infiltration, an increase in
      melanomacrophage number, enlargement of sinusoids, hemorrhage and congestion were
      determined in exposed toads. In kidney tissue, mononuclear cell infiltration,
      hypertrophied Bowman's capsule cells, deformation, vacuolization, karyolysis and
      necrosis of renal tubule epithelium, brush border destruction, glomerular
      shrinkage, hemorrhage and fibrosis were observed in carbaryl-treated groups.
      According to this investigation, carbaryl caused histopathologic damages in liver
      and kidney tissues of B. variabilis. 

PMID- 25573058
TI  - Evidence of a link between taboos and sacrifices and resource scarcity of ritual
      plants.
AB  - BACKGROUND: One of the main obstacles for the mainstreaming of religious
      traditions as tools for the conservation of nature is the limited applicability
      of research results in this field. We documented two different restrictions
      implemented by local people (taboos and sacrifices) related to the use of ritual
      plants in Benin (West Africa) and Gabon (Central Africa). METHODS: To see whether
      these restrictions reflected plant scarcity from an etic perspective (official
      threat status) and an emic viewpoint (perceived scarcity by local people), we
      conducted 102 interviews with traditional healers and adepts of traditional
      faiths. RESULTS: We documented a total of 618 ritual plants, from which 52
      species were used in both countries. In Benin, the use of 63 of the 414 ritual
      plant species was restricted; while in Gabon 23 of the 256 ritual plants were
      associated with taboos and sacrifices. In Benin, restricted plants were
      significantly more often officially threatened, perceived as scarce, and actively
      protected than non-restricted plants. In the more forested and less densely
      populated Gabon, plants that were perceived as scarce were more often associated
      to local restrictions than officially threatened species. CONCLUSIONS: These
      results prove the presence of a form of adaptive management where restrictions
      are related to resource scarcity and protection of ritual plant species. By
      providing baseline data on possibly endangered species, we demonstrate how plant
      use in the context of religious traditions can yield important information for
      conservation planning.

PMID- 25573060
TI  - Akt regulation of Aven contributes to the sensitivity of cancer cells to
      chemotherapeutic agents.
AB  - In the present study, it was demonstrated that the protein level of the apoptosis
      inhibitor Aven is regulated by the Akt signaling pathway, evidenced by the
      observation that Aven levels were significantly increased in MCF7 constitutively
      active (CA)-Akt cells and significantly inhibited following treatment with
      LY294002. This increase in Aven appears not to be mediated by transcriptional
      regulation and protein stabilization. However, the level of Aven was inversely
      correlated with the level of cathepsin D, which is a protease responsible for
      generating the C-terminal of Aven, DeltaN-Aven, indicating that the level of Aven
      appears to be regulated by cathepsin D activity. It has previously been reported
      that DeltaN-Aven is the active form of Aven, which functions as an anti-apoptotic
      molecule. Notably, low levels of DeltaN-Aven were detected in MCF7 CA-Akt cells,
      which were more sensitive to anticancer drugs. Taken together, the current
      results suggest that the expression of Aven is regulated by the Akt signaling
      pathway through cathepsin D activity, which contributes to the sensitivity of
      cancer cells to chemotherapeutic agents.

PMID- 25573059
TI  - Plasma-activated medium suppresses choroidal neovascularization in mice: a new
      therapeutic concept for age-related macular degeneration.
AB  - Choroidal neovascularization (CNV) is the main pathogenesis of age-related
      macular degeneration (AMD), which leads to severe vision loss in many aged
      patients in most advanced country. CNV compromises vision via hemorrhage and
      retinal detachment on account of pathological neovascularization penetrating the
      retina. Plasma medicine represents the medical application of ionized gas
      "plasma" that is typically studied in the field of physical science. Here we
      examined the therapeutic ability of plasma-activated medium (PAM) to suppress
      CNV. The effect of PAM on vascularization was assessed on the basis of human
      retinal endothelial cell (HREC) tube formation. In mice, laser photocoagulation
      was performed to induce CNV (laser-CNV), followed by intravitreal injection of
      PAM. N-Acetylcysteine was used to examine the role of reactive oxygen species in
      PAM-induced CNV suppression. Fundus imaging, retinal histology examination, and
      electroretinography (ERG) were also performed to evaluate PAM-induced retinal
      toxicity. Interestingly, HREC tube formation and laser-CNV were both reduced by
      treatment with PAM. N-acetylcysteine only partly neutralized the PAM-induced
      reduction in laser-CNV. In addition, PAM injection had no effect on regular
      retinal vessels, nor did it show retinal toxicity in vivo. Our findings indicate
      the potential of PAM as a novel therapeutic agent for suppressing CNV. 

PMID- 25573063
TI  - Risk factors for invasive mold diseases in allogeneic hematopoietic cell
      transplant recipients.
AB  - BACKGROUND: The epidemiology of and risk factors for invasive mold disease (IMD)
      among allogeneic hematopoietic cell transplant (HCT) recipients may vary
      according to the region. In this study, we sought to evaluate risk factors for
      IMD in our patient population. METHODS: Between May 2007 and July 2009, all HCT
      recipients from 8 Brazilian centers were followed prospectively until 1 year post
      transplant. Cases of IMD were classified as early (before day +40) or late (after
      day +40). Patients with IMD (cases) were compared with controls (patients without
      IMD) using univariate and multivariate Cox regression analysis. RESULTS: Among
      345 HCT recipients, 28 IMDs were diagnosed. Risk factors for early IMD were acute
      myeloid leukemia (hazard ratio [HR] 2.95, 95% confidence interval [95% CI] 1.13
      7.68, P = 0.03) and transplant with a human leukocyte antigen-mismatched donor
      (HR 3.38, 95% CI 1.18-9.68, P = 0.02), and for late IMD risk factors were
      lymphoma (HR 8.49, 95% CI 2.35-30.68, P = 0.001), cytomegalovirus reactivation
      (HR 5.51, 95% CI 1.15-26.47, P = 0.03), and neutropenia (HR 3.49, 95% CI 1.01
      12.13, P = 0.049). CONCLUSION: The variables identified in this study may help to
      define risk groups, and to tailor special preventive measures to patients at
      higher risk to develop IMD.

PMID- 25573062
TI  - Pathologic-radiologic correlation in evaluation of retroareolar margin in nipple
      sparing mastectomy.
AB  - Nipple-sparing mastectomy (NSM) has recently been increasing in popularity due to
      a better cosmetic outcome and quality-of-life benefit. The radiologic distance
      between the tumor and the nipple is independently predictive of nipple-areolar
      complex involvement and can assist in patient selection for NSM. However,
      concordance between the preoperative radiologic imaging and histologic evaluation
      would play a major role in making patient selection for NSM meaningful. We
      analyzed the pathologic-radiologic correlation for evaluation of retroareolar
      (RA) margin in NSM. A retrospective histologic and blinded radiologic review of
      80 NSM (41 therapeutic and 39 prophylactic) performed on 45 patients was done.
      Histologically, the cases were divided into positive or close (invasive or in
      situ carcinoma within 5 mm of the RA margin) and negative (greater than 5 mm from
      the RA margin). Radiographically, positive cases were defined as suspicious
      enhancement and/or suspicious findings within 20 mm of the nipple on magnetic
      resonance imaging (MRI) and/or diagnostic mammography, respectively. Thirty five
      of 41 (85.4 %) therapeutic cases were concordant. Six cases were discordant, with
      2/41 (4.9 %) discordant cases classified as positive at histology, but negative
      on imaging and 4/41 (9.75 %) discordant cases classified as negative at
      histology, but positive on imaging. Agreement between pathology and radiology was
      moderate [kappa coefficient 0.54 (p = 0.0003)].We conclude that there is a
      significant agreement between histologic and radiologic evaluation for assessment
      of RA margin and preoperative radiologic imaging; specifically, MRI provides
      valuable information and should be strongly recommended to help select patients
      for NSM.

PMID- 25573065
TI  - A novel, safe and cost effective way for teaching corneal foreign body removal.

PMID- 25573064
TI  - Two potential hookworm DAF-16 target genes, SNR-3 and LPP-1: gene structure,
      expression profile, and implications of a cis-regulatory element in the
      regulation of gene expression.
AB  - BACKGROUND: Hookworms infect nearly 700 million people, causing anemia and
      developmental stunting in heavy infections. Little is known about the genomic
      structure or gene regulation in hookworms, although recent publication of draft
      genome assemblies has allowed the first investigations of these topics to be
      undertaken. The transcription factor DAF-16 mediates multiple developmental
      pathways in the free living nematode Caenorhabditis elegans, and is involved in
      the recovery from the developmentally arrested L3 in hookworms. Identification of
      downstream targets of DAF-16 will provide a better understanding of the molecular
      mechanism of hookworm infection. METHODS: Genomic Fragment 2.23 containing a DAF
      16 binding element (DBE) was used to identify overlapping complementary expressed
      sequence tags (ESTs). These sequences were used to search a draft assembly of the
      Ancylostoma caninum genome, and identified two neighboring genes, snr-3 and lpp
      1, in a tail-to-tail orientation. Expression patterns of both genes during
      parasitic development were determined by qRT-PCR. DAF-16 dependent cis-regulatory
      activity of fragment 2.23 was investigated using an in vitro reporter system.
      RESULTS: The snr-3 gene spans approximately 5.6 kb in the genome and contains 3
      exons and 2 introns, and contains the DBE in its 3' untranslated region.
      Downstream from snr-3 in a tail-to-tail arrangement is the gene lpp-1. The lpp-1
      gene spans more than 6 kb and contains 10 exons and 9 introns. The A. caninum
      genome contains 2 apparent splice variants, but there are 7 splice variants in
      the A. ceylanicum genome. While the gene order is similar, the gene structures of
      the hookworm genes differ from their C. elegans orthologs. Both genes show peak
      expression in the late L4 stage. Using a cell culture based expression system,
      fragment 2.23 was found to have both DAF-16-dependent promoter and enhancer
      activity that required an intact DBE. CONCLUSIONS: Two putative DAF-16 targets
      were identified by genome wide screening for DAF-16 binding elements. Aca-snr-3
      encodes a core small nuclear ribonucleoprotein, and Aca-lpp-1 encodes a lipid
      phosphate phosphohydrolase. Expression of both genes peaked at the late L4 stage,
      suggesting a role in L4 development. The 3'-terminal genomic fragment of the snr
      3 gene displayed Ac-DAF-16-dependent cis-regulatory activity.

PMID- 25573066
TI  - A prospective observational study of techniques to remove CFB in the ED; authors'
      reply.

PMID- 25573067
TI  - The challenges of conducting prehospital research: successes and lessons learnt
      from the Head Injury Transportation Straight to Neurosurgery (HITS-NS) trial.
AB  - Head Injury Transportation Straight to Neurosurgery was a cluster randomised
      trial studying suspected severe head injury treatment pathways conducted in the
      North East Ambulance Service NHS Foundation Trust and North West Ambulance
      Service NHS Trust between January 2012 and March 2013. This was the world's first
      large scale trial of any trauma bypass and was conducted as a feasibility study.
      This short report will describe some of the lessons learnt during this ground
      breaking and complex trial. 

PMID- 25573068
TI  - Re: A prospective observational study of techniques to remove corneal foreign
      body in the emergency department.

PMID- 25573071
TI  - The effect of isotretinoin on retinol-binding protein 4, leptin, adiponectin and
      insulin resistance in acne vulgaris patients.
AB  - BACKGROUND: The effect of isotretinoin (ISO) on adipokines and insulin resistance
      has been investigated in a few studies, and the results are conflicting.
      OBJECTIVE: The aim of this study was to investigate the effect of ISO treatment
      on insulin resistance and adipokines. METHODS: Thirty-three patients with acne
      vulgaris and a control group of 30 healthy volunteers were included in our study.
      Screening for the biochemical parameters was performed just before the initiation
      and after 3 months of ISO treatment. RESULTS: In the acne group, basal leptin
      levels were significantly lower (p = 0.003) and basal adiponectin levels
      significantly higher (p = 0.008) compared with the control group. After ISO
      treatment, leptin levels (p = 0.0005) decreased and adiponectin levels (p =
      0.003) increased significantly. However, measurements of fasting blood glucose,
      insulin, C peptide, retinol-binding protein 4 (RBP4), homeostasis model
      assessment insulin resistance and BMI did not differ after ISO treatment.
      CONCLUSION: ISO may affect leptin and adiponectin levels. It does not, however,
      affect insulin resistance and RBP4 levels.

PMID- 25573070
TI  - Effects of Stochastic Vestibular Galvanic Stimulation and LDOPA on Balance and
      Motor Symptoms in Patients With Parkinson's Disease.
AB  - BACKGROUND: Balance problems contribute to reduced quality of life in Parkinson's
      disease (PD) and available treatments are often insufficient for treating axial
      and postural motor symptoms. OBJECTIVE: To investigate the safety of use and
      possible effects of stochastic vestibular stimulation (SVS) alone and combined
      with LDOPA in patients with PD. METHODS: SVS or sham stimulation was administered
      to 10 PD patients in a double-blind placebo controlled cross-over pilot study.
      Motor symptoms and balance were evaluated in a defined off-medication state and
      after a 200 mg test dose of LDOPA, using UPDRS-III, Posturo-Locomotor-Manual
      (PLM) movement times (MT), static posturography and force plate measurements of
      the correcting response to a balance perturbation. RESULTS: Patients did not
      detect when SVS was active, but SVS increased nausea after LDOPA in two patients.
      Mixed model analysis demonstrated that SVS improved balance corrections after a
      backward perturbation and shortened the postural response time. In static
      posturography there was significant interaction between effects of SVS,
      medication and proprioceptive input (standing on foam vs. on hard support) and
      SVS decreased the total sway-path with eyes closed and off medication. As
      expected, LDOPA improved the UPDRS-III scores and MT. There was an interaction
      between the effect of SVS and LDOPA on UPDRS-III partly because of reduced UPDRS
      III scores with SVS in the off-medication state. CONCLUSIONS: Short term use of
      SVS is safe, improves corrective postural responses and may have a small positive
      effect on motor symptoms in PD patients off treatment.

PMID- 25573069
TI  - Non-invasive Access to the Vagus Nerve Central Projections via Electrical
      Stimulation of the External Ear: fMRI Evidence in Humans.
AB  - BACKGROUND: Tract-tracing studies in cats and rats demonstrated that the
      auricular branch of the vagus nerve (ABVN) projects to the nucleus tractus
      solitarii (NTS); it has remained unclear as to whether or not the ABVN projects
      to the NTS in humans. OBJECTIVE: To ascertain whether non-invasive electrical
      stimulation of the cymba conchae, a region of the external ear exclusively
      innervated by the ABVN, activates the NTS and the "classical" central vagal
      projections in humans. METHODS: Twelve healthy adults underwent two fMRI scans in
      the same session. Electrical stimulation (continuous 0.25ms pulses, 25Hz) was
      applied to the earlobe (control, scan #1) and left cymba conchae (scan #2).
      Statistical analyses were performed with FSL. Two region-of-interest analyses
      were performed to test the effects of cymba conchae stimulation (compared to
      baseline and control, earlobe, stimulation) on the central vagal projections
      (corrected; brainstem P < 0.01, forebrain P < 0.05), followed by a whole-brain
      analysis (corrected, P < 0.05). RESULTS: Cymba conchae stimulation, compared to
      earlobe (control) stimulation, produced significant activation of the "classical"
      central vagal projections, e.g., widespread activity in the ipsilateral NTS,
      bilateral spinal trigeminal nucleus, dorsal raphe, locus coeruleus, and
      contralateral parabrachial area, amygdala, and nucleus accumbens. Bilateral
      activation of the paracentral lobule was also observed. Deactivations were
      observed bilaterally in the hippocampus and hypothalamus. CONCLUSION: These
      findings provide evidence in humans that the central projections of the ABVN are
      consistent with the "classical" central vagal projections and can be accessed non
      invasively via the external ear.

PMID- 25573073
TI  - A meta-approach for improving the prediction and the functional annotation of
      ortholog groups.
AB  - BACKGROUND: In comparative genomics, orthologs are used to transfer annotation
      from genes already characterized to newly sequenced genomes. Many methods have
      been developed for finding orthologs in sets of genomes. However, the application
      of different methods on the same proteome set can lead to distinct orthology
      predictions. METHODS: We developed a method based on a meta-approach that is able
      to combine the results of several methods for orthologous group prediction. The
      purpose of this method is to produce better quality results by using the
      overlapping results obtained from several individual orthologous gene prediction
      procedures. Our method proceeds in two steps. The first aims to construct seeds
      for groups of orthologous genes; these seeds correspond to the exact overlaps
      between the results of all or several methods. In the second step, these seed
      groups are expanded by using HMM profiles. RESULTS: We evaluated our method on
      two standard reference benchmarks, OrthoBench and Orthology Benchmark Service.
      Our method presents a higher level of accurately predicted groups than the
      individual input methods of orthologous group prediction. Moreover, our method
      increases the number of annotated orthologous pairs without decreasing the
      annotation quality compared to twelve state-of-the-art methods. CONCLUSIONS: The
      meta-approach based method appears to be a reliable procedure for predicting
      orthologous groups. Since a large number of methods for predicting groups of
      orthologous genes exist, it is quite conceivable to apply this meta-approach to
      several combinations of different methods.

PMID- 25573072
TI  - Combination treatment with triptolide and hydroxycamptothecin synergistically
      enhances apoptosis in A549 lung adenocarcinoma cells through PP2A-regulated ERK,
      p38 MAPKs and Akt signaling pathways.
AB  - Lung cancer is the leading cause of cancer death worldwide. Recently, two plant
      derived drugs triptolide (TP) and hydroxycamptothecin (HCPT) both have shown
      broad-spectrum anticancer activities. Our previous study documented that
      combination treatment with these two drugs acted more effectively than mono
      therapy, however, the molecular basis underlying the synergistic cytotoxicity
      remains poorly understood. In this study, we aimed to clarify the molecular
      mechanism of TP/HCPT anticancer effect in A549 lung adenocarcinoma cells, by
      investigating the involvement of phosphatase 2A (PP2A) and PP2A-regulated mitogen
      activated protein kinases (MAPKs) and Akt signaling pathways. The results showed
      that TP and HCPT synergistically exerted cytotoxicity in the growth of A549
      cells. Combinatorial TP/HCPT treatment significantly enhanced the activation of
      caspase-3 and -9, Bax/Bcl-2 ratio, release of cytochrome c from mitochondrial and
      subsequent apoptosis. While the Akt survival pathway was inhibited, ERK and p38
      MAPKs were dramatically activated. Furthermore, the activity of PP2A was
      significantly augmented. Regulation of p38, ERK and Akt by PP2A was demonstrated,
      by using a specific PP2A inhibitor okadaic acid (OA). Finally, pharmacological
      inhibitors OA, SB203580, SP600125 and PD98059 confirm the role of PP2A and its
      substrates ERK, p38 MAPK and Akt in mediating TP/HCPT-induced apoptosis. Taken
      together, this study provides the first evidence for a synergistic TP/HCPT
      anticancer activity in A549 cells and also supports a critical role of PP2A and
      PP2A-regulated signaling pathways, providing new insight into the mode of action
      of TP/HCPT in cancer therapy.

PMID- 25573075
TI  - Host-sensitized luminescence in LaNbO4:Ln(3+) (Ln(3+) = Eu(3+)/Tb(3+)/Dy(3+))
      with different emission colors.
AB  - In this work, a series of Eu(3+), Tb(3+), and Dy(3+) singly-doped and co-doped
      LaNbO4 (LNO) phosphors have been synthesized by a high-temperature solid-state
      reaction route. X-ray diffraction (XRD) along with Rietveld refinement, diffuse
      reflection spectra, photoluminescence (PL) and cathodoluminescence (CL)
      properties, decay lifetimes, and PL quantum yields (QYs) were exploited to
      characterize the phosphors. Under UV excitation, energy transfer process from the
      host to the activators exists in the singly-doped samples, which leads to tunable
      emission color from blue to red for LNO:Eu(3+), green for LNO:Tb(3+), and yellow
      including white for LNO:Dy(3+). In Eu(3+) and Tb(3+) co-doped phosphors,
      LNO:Eu(3+), Tb(3+), the energy transfers from the host to the activators and
      Tb(3+) to Eu(3+) ions have also been deduced from the PL spectra, resulting in
      tunable emission color from green to red by adjusting the concentration ratio of
      Eu(3+) and Tb(3+) ions. The decay times monitored at host emission and Tb(3+)
      emission confirm the existence of energy transfer in the as-prepared samples. The
      best quantum efficiency can reach 43.2% for LNO:0.01Tb(3+) among all the as
      prepared phosphors. In addition, the CL spectra of LNO:Eu(3+)/Tb(3+)/Dy(3+) are a
      little different from their PL spectra because another emission envelope around
      530 nm appears in the samples, which is attributed to the bombardment of higher
      energy excitation source of low-voltage electron beam. However, the
      characteristic emissions similar to PL spectra were reserved. Moreover, the CL
      spectrum of LNO:0.02Tb(3+) has stronger emission intensity than that of ZnO:Zn
      commercial product. These results from the PL and CL properties of
      LNO:Eu(3+)/Tb(3+)/Dy(3+) suggest their potential in solid-state lighting and
      display fields. 

PMID- 25573074
TI  - GPCR dimerization in brainstem nuclei contributes to the development of
      hypertension.
AB  - BACKGROUND AND PURPOSE: MU-Opioid receptors, pro-opiomelanocortin and pro
      enkephalin are highly expressed in the nucleus tractus solitarii (NTS) and MU
      receptor agonists given to the NTS dose-dependently increased BP. However, the
      molecular mechanisms of this process remain unclear. In vitro, MU receptors
      heterodimerize with alpha2A -adrenoceptors. We hypothesized that alpha2A 
      adrenoceptor agonists would lose their depressor effects when their receptors
      heterodimerize in the NTS with MU receptors. EXPERIMENTAL APPROACH: We
      microinjected MU-opioid agonists and antagonists into the NTS of rats and
      measured changes in BP. Formation of MU receptor/alpha2A -adrenoceptor
      heterodimers was assessed with immunofluorescence and co-immunoprecipitation
      methods, along with proximity ligation assays. KEY RESULTS: Immunofluorescence
      staining revealed colocalization of alpha2A -adrenoceptors and MU receptors in
      NTS neurons. Co-immunoprecipitation revealed interactions between alpha2A 
      adrenoceptors and MU receptors. In situ proximity ligation assays confirmed the
      presence of MU receptor/alpha2A -adrenoceptor heterodimers in the NTS. Higher
      levels of endogenous endomorphin-1 and MU receptor/alpha2A -adrenoceptor
      heterodimers were found in the NTS of hypertensive rats, than in normotensive
      rats. Microinjection of the MU receptor agonist [D-Ala(2) , MePhe(4) , Gly(5) 
      ol]-enkephalin (DAMGO), but not that of the alpha2A -adrenoceptor agonist
      guanfacine, into the NTS of normotensive rats increased MU receptor/alpha2A 
      adrenoceptor heterodimer formation and BP elevation. The NO-dependent BP-lowering
      effect of alpha2A -adrenoceptor agonists was blunted following increased
      formation of MU receptor/alpha2A -adrenoceptor heterodimers in the NTS of
      hypertensive rats and DAMGO-treated normotensive rats. CONCLUSIONS AND
      IMPLICATIONS: Increases in endogenous MU receptor agonists in the NTS induced MU
      receptor/alpha2A -adrenoceptor heterodimer formation and reduced the NO-dependent
      depressor effect of alpha2A -adrenoceptor agonists. This process could contribute
      to the pathogenesis of hypertension.

PMID- 25573077
TI  - Emergency Mental Health Services for Children After the Terrorist Attacks of
      September 11, 2001.
AB  - Much literature documents elevated psychiatric symptoms among adults after the
      terrorist attacks of September 11, 2001 (9/11). We, however, know of no research
      in children that examines emergency mental health services following 9/11. We
      test whether children's emergency services for crisis mental health care rose
      above expected values in September 2001. We applied time-series methods to
      California Medicaid claims (1999-2003; N = 127,200 visits). Findings in
      California indicate an 8.7% increase of children's emergency mental health visits
      statistically attributable to 9/11. Non-Hispanic white more than African American
      children account for this acute rise in emergency services.

PMID- 25573076
TI  - Utility of a dedicated pediatric cardiac anticoagulation program: the Boston
      Children's Hospital experience.
AB  - Congenital heart disease is the leading cause of stroke in children. Warfarin
      therapy can be difficult to manage safely in this population because of its
      narrow therapeutic index, multiple drug and dietary interactions, small patient
      size, high-risk cardiac indications, and lack of data to support anticoagulation
      recommendations. We sought to describe our institution's effort to develop a
      dedicated cardiac anticoagulation service to address the special needs of this
      population and to review the literature. In 2009, in response to Joint Commission
      National Patient Safety Goals for Anticoagulation, Boston Children's Hospital
      created a dedicated pediatric Cardiac Anticoagulation Monitoring Program (CAMP).
      The primary purpose was to provide centralized management of outpatient
      anticoagulation to cardiac patients, to serve as a disease-specific resource to
      families and providers, and to devise strategies to evolve clinical care with
      rapidly emerging trends in anticoagulation care. Over 5 years the CAMP Service,
      staffed by a primary pediatric cardiology attending, a full-time nurse
      practitioner, and administrative assistant with dedicated support from pharmacy
      and nutrition, has enrolled over 240 patients ranging in age from 5 months to 55
      years. The most common indications include a prosthetic valve (34 %), Fontan
      prophylaxis (20 %), atrial arrhythmias (11 %), cardiomyopathy (10 %), Kawasaki
      disease (7 %), and a ventricular assist device (2 %). A patient-centered multi
      disciplinary cardiac anticoagulation clinic was created in 2012. Overall program
      international normalized ratio (INR) time in therapeutic range (TTR) is favorable
      at 67 % (81 % with a 0.2 margin) and has improved steadily over 5 years.
      Pediatric-specific guidelines for VKOR1 and CYP2C9 pharmacogenomics testing,
      procedural bridging with enoxaparin, novel anticoagulant use, and quality metrics
      have been developed. Program satisfaction is rated highly among families and
      providers. A dedicated pediatric cardiac anticoagulation program offers a safe
      and effective strategy to standardize anticoagulation care for pediatric
      cardiology patients, is associated with high patient and provider satisfaction,
      and is capable of evolving care strategies with emerging trends in
      anticoagulation.

PMID- 25573078
TI  - Anti-tumor activity of the TGF-beta receptor kinase inhibitor galunisertib
      (LY2157299 monohydrate) in patient-derived tumor xenografts.
AB  - PURPOSE: The transforming growth factor-beta (TGF-beta) signaling pathway is
      known to play a critical role in promoting tumor growth. Consequently, blocking
      this pathway has been found to inhibit tumor growth. In order to achieve an
      optimal anti-tumor effect, however, it remains to be established whether blocking
      the TGF-beta signaling pathway alone is sufficient, or whether the tumor
      microenvironment plays an additional, possibly synergistic, role. METHODS: To
      investigate the relevance of blocking TGF-beta signaling in tumor cells within
      the context of their respective tissue microenvironments, we treated a panel of
      patient-derived xenografts (PDX) with the selective TGF-beta receptor kinase
      inhibitor LY2157299 monohydrate (galunisertib) and assessed both the in vitro and
      in vivo effects. RESULTS: Galunisertib was found to inhibit the growth in an in
      vitro clonogenic assay in 6.3% (5/79) of the examined PDX. Evaluation of the
      expression profiles of a number of genes, representing both canonical and non
      canonical TGF-beta signaling pathways, revealed that most PDX exhibited
      expression changes affecting TGF-beta downstream signaling. Next, we subjected 13
      of the PDX to an in vivo assessment and, by doing so, observed distinct response
      patterns. These results suggest that, next to intrinsic, also extrinsic or
      microenvironmental factors can affect galunisertib response. pSMAD2 protein
      expression and TGF-betaRI mRNA expression levels were found to correlate with the
      in vivo galunisertib effects. CONCLUSIONS: From our data we conclude that
      intrinsic, tumor-dependent TGF-beta signaling does not fully explain the anti
      tumor effect of galunisertib. Hence, in vivo xenograft models may be more
      appropriate than in vitro clonogenic assays to assess the anti-tumor activity of
      TGF-beta inhibitors such as galunisertib.

PMID- 25573080
TI  - Economics-questions rather than answers.

PMID- 25573081
TI  - The genus Trollius-review of pharmacological and chemical research.
AB  - Three species of the genus Trollius (Ranunculaceae) are traditionally used to
      treat upper respiratory tract infections, pharyngitis, tonsillitis, bronchitis,
      cold with fever, acute tympanitis, aphthae, mouth sore, hemorrhage and pain of
      gums, acute lymphangitis and acute periostitis. However, only a few studies
      support its traditional use. These are studies of the biological activity of
      extracts and/or compounds of selected species of Trollius, but there are no
      clinical studies proving the effectiveness or possible toxic effects. Until now,
      the following activity of extracts and/or compounds from certain species of
      Trollius used in traditional medicine has been proven: antiviral, antibacterial,
      antiinflammatory and antioxidant. The review showed that flavonoids, mainly C
      glycosides, were characteristic of the species Trollius. Furthermore, other main
      groups of compounds are carotenoids, organic acids, terpenes, alkaloids, sterols,
      lactones and carbohydrates. The essential oil mainly contains compounds from the
      group of benzenoids, nitrogen-containing compounds, monoterpenoids and
      sesquiterpenoids, irregular terpenes and macrocyclic epoxide.

PMID- 25573082
TI  - Controlling the redox properties of a pyrroloquinolinequinone (PQQ) derivative in
      a ruthenium(II) coordination sphere.
AB  - Ruthenium(ii) complexes of PQQTME, a trimethyl ester derivative of redox-active
      PQQ (pyrroloquinolinequinone), were prepared using a tridentate ligand,
      2,2':6',2''-terpyridine (terpy) as an auxiliary ligand. The characterization of
      the complexes was performed by spectroscopic methods, X-ray crystallography, and
      electrochemical measurements. In one complex, the pyridine site of PQQTME binds
      to the [Ru(II)(terpy)] unit as a tridentate ligand, and a silver(i) ion is
      coordinated by the quinone moiety in a bidentate fashion. In contrast, another
      complex includes the [Ru(II)(terpy)] unit at the bidentate quinone moiety of the
      PQQTME ligand. The difference in the coordination modes of the complexes exhibits
      a characteristic difference in the stability of metal coordination and also in
      the reversibility of the reduction processes of the PQQTME ligand. It should be
      noted that an additional metal-ion-binding to the PQQTME ligand largely raises
      the 1e(-)-reduction potential of the ligand. In addition, we succeeded in the
      characterization of the 1e(-)-reduced species of the complexes, where the
      unpaired electron was delocalized in the pi-conjugated system of the PQQTME(-)
      ligand, using UV-Vis absorption and ESR spectroscopies. 

PMID- 25573083
TI  - Expression and functional activity of the bitter taste receptors TAS2R1 and
      TAS2R38 in human keratinocytes.
AB  - Recent studies have shown that human bitter taste receptors (TAS2Rs) are not only
      expressed in mucous epithelial cells of the tongue, but also in epithelial cells
      of the colon, stomach and upper respiratory tract. These cell types come in close
      contact with external bitter compounds by ingestion or breathing. In the present
      work we addressed the question whether bitter taste receptors might also be
      expressed in cornified epithelial cells of the skin. Here, we show for the first
      time the expression of TAS2R1 and TAS2R38 in human skin. Double staining of HaCaT
      cells and primary keratinocytes demonstrated the colocalization of TAS2R1 and
      TAS2R38 with the adaptor protein alpha-gustducin that is essential for signal
      transduction upon ligand binding. To test if TAS2Rs in keratinocytes are
      functional, we stimulated HaCaT cells with diphenidol, a clinically used bitter
      tasting antiemetic, or amarogentin, the bitterest plant substance, that binds
      TAS2Rs, including TAS2R1 and TAS2R38. Diphenidol and amarogentin induced calcium
      influx. Furthermore, in keratinocytes diphenidol and amarogentin stimulated the
      expression of the differentiation markers keratin 10, involucrin and
      transglutaminase. Therefore, apart from the known role in mucous membranes of the
      gastrointestinal tract, TAS2Rs are expressed in the epidermis and might play a
      role in keratinocyte differentiation.

PMID- 25573084
TI  - [Bright ocular background with profound cutis laxa and large fontanelles].

PMID- 25573079
TI  - Germline oncopharmacogenetics, a promising field in cancer therapy.
AB  - Pharmacogenetics (PGx) is the study of the relationship between inter-individual
      genetic variation and drug responses. Germline variants of genes involved in drug
      metabolism, drug transport, and drug targets can affect individual response to
      medications. Cancer therapies are characterized by an intrinsically high
      toxicity; therefore, the application of pharmacogenetics to cancer patients is a
      particularly promising method for avoiding the use of inefficacious drugs and
      preventing the associated adverse effects. However, despite continuing efforts in
      this field, very few labels include information about germline genetic variants
      associated with drug responses. DPYD, TPMT, UGT1A1, G6PD, CYP2D6, and HLA are the
      sole loci for which the European Medicines Agency (EMA) and the US Food and Drug
      Administration (FDA) report specific information. This review highlights the
      germline PGx variants that have been approved to date for anticancer treatments,
      and also provides some insights about other germline variants with potential
      clinical applications. The continuous and rapid evolution of next-generation
      sequencing applications, together with the development of computational methods,
      should help to refine the implementation of personalized medicine. One day,
      clinicians may be able to prescribe the best treatment and the correct drug
      dosage based on each patient's genotype. This approach would improve treatment
      efficacy, reduce toxicity, and predict non-responders, thereby decreasing
      chemotherapy-associated morbidity and improving health benefits. 

PMID- 25573086
TI  - Enhanced performance in fluorene-free organometal halide perovskite light
      emitting diodes using tunable, low electron affinity oxide electron injectors.
AB  - Fluorene-free perovskite light-emitting diodes (LEDs) with low turn-on voltages,
      higher luminance and sharp, color-pure electroluminescence are obtained by
      replacing the F8 electron injector with ZnO, which is directly deposited onto the
      CH3NH3PbBr3 perovskite using spatial atmospheric atomic layer deposition. The
      electron injection barrier can also be reduced by decreasing the ZnO electron
      affinity through Mg incorporation, leading to lower turn-on voltages.

PMID- 25573085
TI  - [Laser treatment or intravitreal VEGF inhibition for aggressive posterior
      retinopathy of prematurity?].
AB  - A prematurely born male infant (24+5 gestational weeks, birth weight 485 g) was
      diagnosed with bilateral aggressive posterior retinopathy of prematurity (AP-ROP)
      in zone I. After obtaining informed written consent from the parents, one eye was
      treated with diode laser photocoagulation and the other eye with 0.25 mg
      intravitreal ranibizumab. Laser photocoagulation was found to be an effective
      tool for fast regression of AP-ROP; however, medium-term evaluation showed poor
      macular formation and peripheral retinal detachment. The intravitreal injection
      led to a slower but better control of the AP-ROP and central foveal reflexes
      showed better anatomical outcome.

PMID- 25573087
TI  - Rescue of cortical neurovascular functions during the hyperacute phase of
      ischemia by peripheral sensory stimulation.
AB  - To investigate the potential therapeutic effects of peripheral sensory
      stimulation during the hyperacute phase of stroke, the present study utilized
      electrophysiology and photoacoustic imaging techniques to evaluate neural and
      vascular responses of the rat cortex following ischemic insult. We employed a rat
      model of photothrombotic ischemia (PTI), which targeted the forelimb region of
      the primary somatosensory cortex (S1FL), due to its high reproducibility in
      creating localized ischemic injury. We also established a hybrid, dual-modality
      system, including six-channel electrocorticography (ECoG) and functional
      photoacoustic microscopy (fPAM), termed ECoG-fPAM, to image brain functional
      responses to peripheral sensory stimulation during the hyperacute phase of PTI.
      Our results showed that the evoked cerebral blood volume (CBV) and hemoglobin
      oxygen saturation (SO2) recovered to 84+/-7.4% and 79+/-6.2% of the baseline,
      respectively, when stimulation was delivered within 2.5 h following PTI
      induction. Moreover, neural activity significantly recovered, with 77+/-8.6%,
      76+/-5.3% and 89+/-8.2% recovery for the resting-state inter-hemispheric
      coherence, alpha-to-delta ratio (ADR) and somatosensory evoked potential (SSEP),
      respectively. Additionally, we integrated the CBV or SO2 with ADR values as a
      recovery indicator (RI) to assess functional recovery after PTI. The RI indicated
      that 80+/-4.2% of neurovascular function was preserved when stimulation was
      delivered within 2.5h. Additionally, stimulation treatment within this optimal
      time window resulted in a minimal infarct volume in the ischemic hemisphere
      (4.6+/-2.1%). In contrast, the infarct volume comprised 13.7+/-1.7% of the
      ischemic hemisphere when no stimulation treatment was applied.

PMID- 25573088
TI  - A longitudinal study of CEACAM1 expression in melanoma disease progression.
AB  - The present study characterized the carcinoembryonic antigen-related cell
      adhesion molecule 1 (CEACAM1) expression profile in a longitudinal study during
      melanoma progression, in lesions obtained from the same patients: a primary skin
      lesion, a lymph node and a distant metastasis. The present study is expected to
      increase our understanding of the expression patterns of CEACAM1 in melanoma
      development. We identified 20 patients who could be analyzed for CEACAM1
      expression over the course of disease progression. The pathology blocks were cut,
      and two slides were generated for each specimen. One underwent standard
      hematoxylin and eosin (H&E) staining and a corresponding slide underwent
      immunohistochemical staining for the detection of CEACAM1. For 13 patients who
      were able to be followed up serially from primary lesion, lymph node and distant
      metastasis, a borderline significant increase in the staining of the membrane was
      noted (P=0.06). In contrast, there was no equivalent increase in cytoplasmic
      CEACAM1 in the same group of patients. For the cohort of 20 patients with primary
      and distant metastasis, a significant increase in the membrane staining was noted
      (P=0.026) and again, no equivalent significant increase in cytoplasmic staining
      was observed. We report that CEACAM1 expression increases along the course of
      disease development and progression of a patient. CEACAM1 represents a novel area
      of research which may have profound influence in future methods of harnessing
      cellular immunity to combat this disease. The results of the present study
      confirm that CEACAM1 is potentially an extremely useful target in arresting
      melanoma progression.

PMID- 25573089
TI  - A qualitative study of choosing home health care after hospitalization: the
      unintended consequences of 'patient choice' requirements.
AB  - BACKGROUND: Although hospitals are increasingly held accountable for patients'
      post-discharge outcomes, giving them incentive to help patients choose high
      performing home health agencies, little is known about how quality reports inform
      decision making. OBJECTIVE: We aimed to learn how quality reports are used when
      choosing home care in one northeast state (Rhode Island) . DESIGN: The study
      consisted of focus groups with home health consumers and structured interviews
      with hospital case managers. PARTICIPANTS: Thirteen consumers and 28 case
      managers from five hospitals participated in the study. APPROACH: We identified
      key themes and illustrative quotes by audiotaping each session, and then three
      independent reviewers conducted repeated examination and content analysis. KEY
      RESULTS: No participants were aware of existing state or Medicare home health
      agency public reports. Case managers provided agency lists to consumers, who
      routinely asked case managers to tell them which agencies to choose or which were
      best; but case managers felt unable to directly respond to consumers' requests
      for help in making the choice, because they did not have additional information
      to provide and because they feared violating federal laws requiring freedom of
      patient choice. Case managers also felt that there was little difference in
      agency quality, although they acknowledged they might not be aware of problems
      related to post-hospital care. CONCLUSIONS: Home health consumers and hospital
      case managers were unaware of public reports about home health quality, which
      limited consumers' ability to make informed decisions and case managers' ability
      to assist them in that decision-making process. Case managers were otherwise
      prohibited from recommending specific providers to patients and viewed the
      'patient choice' laws as restricting their ability to respond to patients'
      requests for help in choosing home health agencies. Public reports can be
      marketed as tools that case managers can use to help patients differentiate among
      providers, while supporting patient autonomy.

PMID- 25573090
TI  - Longitudinal evaluation of the prevalence of overweight/obesity in children with
      congenital heart disease.
AB  - BACKGROUND: Regarding long-term cardiovascular health, obesity may have greater
      implications for children with congenital heart disease (CHD). We sought to
      determine trends in anthropometry over time and its association with exercise
      capacity. METHODS: Medical records of pediatric patients with CHD were randomly
      sampled. Serial measurements of weight and height were abstracted, body mass
      index (BMI) was calculated, and measurements were converted to percentiles and z
      scores. Analyses of trends were performed using regression models adjusted for
      repeated measures. RESULTS: Median follow-up after diagnosis for 725 patients was
      7.1 years (interquartile range, 1.9-12.8 years). The median initial weight z
      score was -1.1 (fifth/95th percentile, -3.6/+1.1) and increased over time (+0.103
      [0.007] standard deviations [SD]/y; P < 0.001). BMI and height z scores could
      only be calculated for patients > 2 years old; at that age, the median BMI z
      score was -0.2 (fifth/95th percentile, -2.6/+1.9) and increased over time (+0.042
      [0.007] SD/y; P < 0.001), whereas the median height z score was -0.3 (fifth/95th
      percentile, -2.7/+1.4) with no change over time (-0.007 [0.006] SD/y; P = 0.18).
      Using standard BMI percentile cut points to define overweight and obesity, 28% of
      patients had at least 1 BMI measurement indicating overweight and 17% indicating
      obesity. Available exercise test results (n = 153) showed that overweight/obese
      patients had lower percent predicted maximum oxygen consumption (-16 [2]%; P <
      0.001), higher peak systolic blood pressure (+11 [4] mm Hg; P = 0.002), and
      higher systolic blood pressure response (+7 [3] mm Hg; P = 0.01) than normal
      weight patients. CONCLUSIONS: In conclusion, children with repaired CHD have an
      important risk of overweight/obesity over time that may increase their
      cardiovascular risk and impair their exercise capacity.

PMID- 25573091
TI  - Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands
      and decrease the risk of xerostomia.
AB  - BACKGROUND: Large anatomical variations occur during the course of intensity
      modulated radiation therapy (IMRT) for locally advanced head and neck cancer
      (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia
      increase. The purposes of the study were to estimate: - the PG overdose and the
      xerostomia risk increase during a "standard" IMRT (IMRTstd); - the benefits of an
      adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of
      xerostomia. MATERIAL AND METHODS: Fifteen patients received radical IMRT (70 Gy)
      for LAHNC. Weekly CTs were used to estimate the dose distributions delivered
      during the treatment, corresponding either to the initial planning (IMRTstd) or
      to weekly replanning (ART). PGs dose were recalculated at the fraction, from the
      weekly CTs. PG cumulated doses were then estimated using deformable image
      registration. The following PG doses were compared: pre-treatment planned dose,
      per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia
      were also compared. Correlations between anatomical markers and dose differences
      were searched. RESULTS: Compared to the initial planning, a PG overdose was
      observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy
      (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of
      xerostomia. Compared to the initial planning, weekly replanning reduced the PG
      mean dose for all the patients (p<0.05). In the overirradiated PG group, weekly
      replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute
      risk of xerostomia by 11% (p<0.01) (30% maximum). The PG overdose and the
      dosimetric benefit of replanning increased with the tumor shrinkage and the neck
      thickness reduction (p<0.001). CONCLUSION: During the course of LAHNC IMRT,
      around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG
      mean dose by 5 Gy, and therefore by 11% the xerostomia risk.

PMID- 25573092
TI  - Insulin restores L-arginine transport requiring adenosine receptors activation in
      umbilical vein endothelium from late-onset preeclampsia.
AB  - INTRODUCTION: Preeclampsia is associated with impaired placental vasodilation and
      reduced endothelial nitric oxide synthase (eNOS) activity in the foetoplacental
      circulation. Adenosine and insulin stimulate vasodilation in endothelial cells,
      and this activity is mediated by adenosine receptor activation in uncomplicated
      pregnancies; however, this activity has yet to be examined in preeclampsia. Early
      onset preeclampsia is associated with severe placental vasculature alterations
      that lead to altered foetus growth and development, but whether late-onset
      preeclampsia (LOPE) alters foetoplacental vascular function is unknown. METHODS:
      Vascular reactivity to insulin (0.1-1000 nmol/L, 5 min) and adenosine (1 mmol/L,
      5 min) was measured in KCl-preconstricted human umbilical vein rings from normal
      and LOPE pregnancies using a wire myograph. The protein levels of human cationic
      amino acid transporter 1 (hCAT-1), adenosine receptor subtypes, total and Ser1177
      or Thr495-phosphorylated eNOS were detected via Western blot, and L-arginine
      transport (0-1000 MUmol/L L-arginine, 3 MUCi/mL L-[3H]arginine, 20 s, 37  degrees
      C) was measured in the presence or absence of insulin and adenosine receptor
      agonists or antagonists in human umbilical vein endothelial cells (HUVECs) from
      normal and LOPE pregnancies. RESULTS: LOPE increased the maximal L-arginine
      transport capacity and hCAT-1 and eNOS expression and activity compared with
      normal conditions. The A(2A) adenosine receptor (A(2A)AR) antagonist ZM-241385
      blocked these effects of LOPE. Insulin-mediated umbilical vein ring relaxation
      was lower in LOPE pregnancies than in normal pregnancies and was restored using
      the A(2A)AR antagonist. DISCUSSION AND CONCLUSIONS: The reduced foetoplacental
      vascular response to insulin may result from A(2A)AR activation in LOPE
      pregnancies.

PMID- 25573094
TI  - Anterior placental location influences onset and progress of labor and postpartum
      outcome.
AB  - INTRODUCTION: The aim of the study is to evaluate whether placental location at
      term is associated with delivery outcome. METHODS: A prospective study including
      2354 patients with singleton pregnancy at term admitted for vaginal delivery was
      conducted. Placental position was determined before delivery by ultrasonographic
      examination performed transabdominally with women in the supine position.
      Maternal characteristics and delivery outcome such as premature rupture of
      membranes, induction of labor, mode and gestational age at delivery, indication
      for cesarean section, duration of the third stage, postpartum hemorrhage (PPH)
      and manual removal of placenta were correlated with anterior, posterior or fundal
      placental locations. RESULTS: Among women enrolled: i) 1164 had an anterior
      placenta, ii) 1087 a posterior placenta, iii) 103 a fundal placenta. Women with
      anterior placenta showed: i) a higher incidence of induction of labor (p =
      0.0001), especially for postdate pregnancies and prolonged prelabor rupture of
      membranes (p < 0.0001), ii) a higher rate of cesarean section rate for failure to
      progress in labor (p = 0.02), iii) a prolonged third stage (p = 0.01), iv) a
      higher incidence of manual removal of placenta (p = 0.003) and a higher rate of
      PPH in vaginal deliveries (p = 0.02). DISCUSSION: The present study showed the
      influence of anterior placental location on the course of labor, with a later
      onset of labor, a higher rate of induction and cesarean section and postpartum
      complications. The reason for this influence on labor and delivery complications
      remains to be elucidated.

PMID- 25573093
TI  - Discordant HIF1A mRNA levels and oxidative stress in placental shares of
      monochorionic twins with selective intra-uterine growth restriction.
AB  - INTRODUCTION: Oxidative stress is a key factor in the pathogenesis of intra
      uterine growth restriction in singleton. However, its role in selective intra
      uterine growth restriction (sIUGR) in monochorionic twins (MCT) is still unknown.
      This study explored the characteristics of oxidative stresses in the placenta
      shares of MCT and analyzed their possible connections with sIUGR. METHODS: The
      placental levels of hypoxia inducible factor-1alpha gene (HIF1A)mRNA,
      malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) were evaluated in
      normal MCT (Group A) and sIUGR MCT (Group B). The results were compared between
      the placental shares of the larger twins (A1/B1) and smaller twins (A2/B2).
      RESULTS: Placental HIF1A mRNA level significantly increased in Group B.
      Particularly, HIF1A mRNA level was elevated in the placenta share of the growth
      restricted fetus (B2) than the co-twin (B1) (P = 0.036). More discordant HIF1A
      mRNA level was detected in Group B than Group A with larger inter-twin difference
      (P = 0.021). The levels of MDA and 8-OHdG were significantly higher in B2 than B1
      in sIUGR MCT (P < 0.05). Both the inter-twin differences of MDA and 8-OHdG were
      also significantly larger in Group B (P < 0.05), indicating that discordant
      oxidative stress existed in the placental shares of sIUGR pregnancies. Finally,
      MDA concentration was found inversely correlated with neonatal birth weight, in
      both sIUGR (r = -0.650, P = 0.022) and normal MCT (r = -0.632, P = 0.027)
      pregnancies. DISCUSSION: The elevation of HIF1A mRNA, and MDA/8-OHdG levels in
      placenta shares of sIUGR MCT suggests that oxidative stress may be involved in
      the pathogenesis of sIUGR.

PMID- 25573096
TI  - Episodic memory impairment in systemic lupus erythematosus: involvement of
      thalamic structures.
AB  - Episodic memory deficits in systemic lupus erythematosus (SLE) have been
      frequently reported in the literature; however, little is known about the neural
      correlates of these deficits. We investigated differences in the volumes of
      different brain structures of SLE patients with and without episodic memory
      impairments diagnosed by the Rey Auditory Verbal Learning Test (RAVLT). Groups
      were paired based on age, education, sex, Mini Mental State Examination score,
      accumulation of disease burden (SLICC), and focused attention dimension score.
      Patients underwent magnetic resonance imaging (MRI). Cortical volumetric
      reconstruction and segmentation of the MR images were performed with the
      FreeSurfer software program. SLE patients with episodic memory deficits presented
      shorter time of diagnosis than SLE patients without episodic memory deficits.
      ANOVA revealed that SLE patients with episodic memory deficits had a larger third
      ventricle volume than SLE patients without episodic memory deficits and controls.
      Additionally, covariance analysis indicated group effects on the bilateral
      thalamus and on the third ventricle. Our findings indicate that episodic memory
      may be impaired in SLE patients with normal hippocampal volume. In addition, the
      thalamus may undergo volumetric changes associated with episodic memory loss in
      SLE. 

PMID- 25573097
TI  - Thr175-phosphorylated tau induces pathologic fibril formation via GSK3beta
      mediated phosphorylation of Thr231 in vitro.
AB  - We have previously shown that amyotrophic lateral sclerosis with cognitive
      impairment can be characterized by pathologic inclusions of microtubule
      associated protein tau (tau) phosphorylated at Thr(175) (pThr(175)) in
      association with GSK3beta activation. We have now examined whether pThr(175)
      induces GSK3beta activation and whether this leads to pathologic fibril formation
      through Thr(231) phosphorylation. Seventy-two hours after transfection of Neuro2A
      cells with pseudophosphorylated green fluorescent protein-tagged 2N4R tau
      (Thr(175)Asp), phosphorylated kinase glycogen synthase kinase 3 beta (active
      GSK3beta) levels were significantly increased as was pathologic fibril formation
      and cell death. Treatment with each of 4 GSK3beta inhibitors or small hairpin RNA
      knockdown of GSK3beta abolished fibril formation and prevented cell death.
      Inhibition of Thr(231) phosphorylation (Thr(231)Ala) prevented pathologic tau
      fibril formation, regardless of Thr(175) state, whereas Thr(231)Asp
      (pseudophosphorylated at Thr(231)) developed pathologic tau fibrils. Ser(235)
      mutations did not affect fibril formation, indicating an unprimed mechanism of
      Thr(231) phosphorylation. These findings suggest a mechanism of tau pathology by
      which pThr(175) induces GSK3beta phosphorylation of Thr(231) leading to fibril
      formation, indicating a potential therapeutic avenue for amyotrophic lateral
      sclerosis with cognitive impairment. 

PMID- 25573098
TI  - Expression of ERCC1, TYMS, RRM1, TUBB3, non-muscle myosin II, myoglobin and MyoD1
      in lung adenocarcinoma pleural effusions predicts survival in patients receiving
      platinum-based chemotherapy.
AB  - The association between the expression of excision repair cross-complementing
      gene 1 (ERCC1), thymidylate synthase (TYMS), ribonuleotide reductase M1 (RRM1),
      betaIII-tubulin (TUBB3), non-muscle myosin II, myoglobin and MyoD1 in metastatic
      lung adenocarcinoma, and clinical outcomes with platinum-based chemotherapy
      treatment is not well-established. Recently, increasing attention has been
      focused on the involvement of ERCC1, TYMS, RRM1 and TUBB3 in the development of
      drug resistance. There has been less research into the role of muscle myosin II,
      myoglobin and MyoD1 in the pathogenesis of lung cancer, although these genes are
      known to have important functions within tumor cells. In the current study,
      malignant pleural effusion from 116 patients with untreated lung adenocarcinoma
      diagnosed between 2011 and 2012, were collected. The protein expression levels of
      ERCC1, TYMS, RRM1 and TUBB3 were evaluated with immunocytochemistry and western
      blot analysis. The expression levels of non-muscle myosin II, myoglobin and MyoD1
      were measured in a subset of 50 patients, treated with platinum-based
      chemotherapy. The association of each of these seven factors with one another, as
      well as with patient survival were analyzed. Immunohistochemistry demonstrated
      that the percentage of pleural fluid samples from patients with lung
      adenocarcinoma expressing ERCC1, TYMS, RRM1 and TUBB3 was 37, 36.2, 82.7 and
      69.8%, respectively. In the subset of 50 patients in whom the remaining factors
      were analyzed, the percentage expressing non-muscle myosin II was 48%, for
      myoglobin the figure was 40% and for MyoD1 it was 38%. There was a positive
      correlation between each pair of the above seven molecules with the exception of
      TYMS and RRM1. Expression of ERCC1, TYMS, TUBB3, non-muscle myosin II, myoglobin
      and MyoD1 genes was associated with decreased survival in patients with
      metastatic lung adenocarcinoma. Expression of ERCC1, TYMS, TUBB3, non-muscle
      myosin II, myoglobin and MyoD1 was also associated with decreased survival rates
      of patients with lung adenocarcinoma treated with platinum-based chemotherapy.
      These factors may be used as clinical biomarkers to predict the biological
      behavior and chemoresistance of tumor cells, and the survival of patients with
      lung carcinoma.

PMID- 25573099
TI  - Nonlinear dynamics of the human lumbar intervertebral disc.
AB  - Systems with a quasi-static response similar to the axial response of the
      intervertebral disc (i.e. progressive stiffening) often present complex dynamics,
      characterized by peculiar nonlinearities in the frequency response. However, such
      characteristics have not been reported for the dynamic response of the disc. The
      accurate understanding of disc dynamics is essential to investigate the unclear
      correlation between whole body vibration and low back pain. The present study
      investigated the dynamic response of the disc, including its potential nonlinear
      response, over a range of loading conditions. Human lumbar discs were tested by
      applying a static preload to the top and a sinusoidal displacement at the bottom
      of the disc. The frequency of the stimuli was set to increase linearly from a low
      frequency to a high frequency limit and back down. In general, the response
      showed nonlinear and asymmetric characteristics. For each test, the disc had
      different response in the frequency-increasing compared to the frequency
      decreasing sweep. In particular, the system presented abrupt changes of the
      oscillation amplitude at specific frequencies, which differed between the two
      sweeps. This behaviour indicates that the system oscillation has a different
      equilibrium condition depending on the path followed by the stimuli. Preload and
      amplitude of the oscillation directly influenced the disc response by changing
      the nonlinear dynamics and frequency of the jump-phenomenon. These results show
      that the characterization of the dynamic response of physiological systems should
      be readdressed to determine potential nonlinearities. Their direct effect on the
      system function should be further investigated. 

PMID- 25573100
TI  - Intercellular adhesion molecule-1 expression in activated eosinophils is
      associated with mucosal remodeling in nasal polyps.
AB  - Nasal polyposis (NP) is characterized by chronic mucosal inflammation with
      infiltrating eosinophils. Eosinophil-mediated tissue remodeling may be involved
      in NP pathogenesis; therefore, improved understanding of tissue remodeling may
      result the identification of novel pathways and therapeutic strategies. The
      present study aimed to investigate the pathological changes occurring during
      tissue remodeling in NP, in order to assess the role of intercellular adhesion
      molecule-1 (ICAM-1) in localized tissue remodeling and the potential association
      between ICAM-1 expression and markers of eosinophil activation. A total of 28
      eligible patients and 10 healthy controls participated in the current study.
      Nasal mucosal tissues of these subjects were retrospectively evaluated for
      mucosal remodeling using histopathological staining. ICAM-1 and eosinophil
      cationic protein (ECP) expression levels were determined by immunohistochemical
      analysis. Compared with the healthy controls, all the specimens from NP patients
      presented substantial epithelial damage, skewed cellular distribution with a
      reduced density of goblet cells, an increased density of subepithelial gland and
      increased subepithelial collagen deposition. In addition, the NP specimens
      exhibited significantly higher eosinophil infiltration and ICAM-1 expression
      compared with the controls. Positive correlations were observed between ICAM-1
      and ECP expression levels (P=0.010), as well as between extracellular collagen
      deposition and ICAM-1 (P=0.010) and ECP (P=0.012) expression levels in the NP
      specimens, but not in the control specimens. Morphological evidence demonstrated
      eosinophil-mediated tissue remodeling in NP tissues. ICAM-1 expression in
      activated eosinophils was associated with NP remodeling, indicating the
      possibility that ICAM-1 may regulate NP remodeling.

PMID- 25573101
TI  - SK053 triggers tumor cells apoptosis by oxidative stress-mediated endoplasmic
      reticulum stress.
AB  - Thioredoxins (Trx) together with thioredoxin reductases (TrxR) participate in the
      maintenance of protein thiol homeostasis and play cytoprotective roles in tumor
      cells. Therefore, thioredoxin-thioredoxin reductase system is considered to be a
      promising therapeutic target in cancer treatment. We have previously reported
      that SK053, a peptidomimetic compound targeting the thioredoxin-thioredoxin
      reductase system, induces oxidative stress and demonstrates antitumor activity in
      mice. In this study, we investigated the mechanisms of SK053-mediated tumor cell
      death. Our results indicate that SK053 induces apoptosis of Raji cells
      accompanied by the activation of the endoplasmic reticulum (ER) stress and
      induction of unfolded protein response. Incubation of tumor cells with SK053
      induces increase in BiP, CHOP, and spliced XBP-1 levels, which precede induction
      of apoptosis. CHOP-deficient (CHOP(-/-)) mouse embryonic fibroblasts are more
      resistant to SK053-induced apoptosis as compared with normal fibroblasts
      indicating that the apoptosis of tumor cells depends on the expression of this
      transcription factor. Additionally, the ER-stress-induced apoptosis, caused by
      SK053, is strongly related with Trx expression levels. Altogether, our results
      indicate that SK053 induces ER stress-associated apoptosis and reveal a link
      between thioredoxin inhibition and induction of UPR in tumor cells. 

PMID- 25573102
TI  - Vaccines have sex differential non-targeted heterologous effects: a new dawn in
      vaccine research.

PMID- 25573103
TI  - Ready to benefit from training: heterologous effects of early life immunization.
AB  - Trained immunity reflects the ability of the innate immune system to adapt via
      epigenetic changes in monocytes, enhancing responses to a range of microbes,
      thereby potentially reducing infection in high-risk populations. Examples of
      trained immunity at birth include enhanced resistance to infection in TLR
      simulated newborn mice, reduced risk of late onset sepsis with histologic
      chorioamnionitis and beneficial heterologous effects of neonatal bacille Calmette
      Guerin administration in reducing diverse infections during infancy. Future
      efforts will assess leveraging trained immunity in early life by administering
      'stand-alone' innate immune stimuli or (self-)adjuvanted vaccines to protect
      against a broad range of infections. 

PMID- 25573104
TI  - The heterologous (non-specific) effects of vaccines: implications for policy in
      high-mortality countries.
AB  - There are important interactions between vaccines, and between vaccines and
      unrelated (heterologous) infections. In high-mortality regions, until the next
      vaccine is given, live vaccines such as bacillus Calmette-Guerin (BCG) and
      measles vaccines reduce mortality from infections such as pneumonia and sepsis.
      However, non-live vaccines such as diphtheria, tetanus and whole-cell pertussis
      vaccine (DTP) may increase mortality from infections other than diphtheria,
      tetanus and pertussis. All-cause mortality might be reduced if an extra dose of
      Edmonston-Zagreb measles vaccine were given at 20 weeks of age, 4-6 weeks after
      the third dose of DTP, with no subsequent doses of DTP in girls, and no vitamin A
      in girls or boys before the second dose of measles vaccine at 9 months of age.
      Policy should change to increase the proportion of babies given BCG and oral
      polio vaccine at birth, and should recognize the important differences between
      BCG, DTP and measles vaccines produced by different manufacturers. 

PMID- 25573106
TI  - Is early measles vaccination better than later measles vaccination?
AB  - WHO recommends delaying measles vaccination (MV) until maternal antibody has
      waned. However, early MV may improve child survival by reducing mortality from
      conditions other than measles infection. We tested whether early MV improves
      child survival compared with later MV. We found 43 studies comparing measles
      vaccinated and measles-unvaccinated children; however, only 16 studies had
      specific information that MV had been provided at 4-13 months of age, many before
      9 months of age. In the 10 best studies (4 randomized trials and 6 observational
      studies) control children did not receive MV during follow-up. In eight of these
      studies the vaccine efficacy against death (VED) was 60% or more. In four studies
      with information on MV provided both before and after 12 months of age, the all
      cause mortality reduction was significantly larger for children vaccinated in
      infancy (VED=74%; 95% CI 51-86%) than for children vaccinated after 12 months of
      age (VED=29%; CI 8-46%). Prevention of measles explained little of the reduction
      in mortality. In five studies with information on measles infection, VED was 67%
      (51-78%) and when measles deaths were excluded, VED was only reduced to 65% (47
      77%). One natural experiment compared MV at 4-8 months versus MV at 9-11 months
      of age and found significantly lower all-cause mortality with early vaccination,
      the difference being 39% (8-60%). Child mortality may be reduced if MV is given
      earlier than currently recommended by international organizations. 

PMID- 25573107
TI  - Trained immunity: consequences for the heterologous effects of BCG vaccination.
AB  - A growing body of evidence from epidemiologic and immunologic studies have shown
      that in addition to target disease-specific effects, vaccines have heterologous
      effects towards unrelated pathogens. Like some other vaccines, bacille Calmette
      Guerin (BCG) has shown in observational studies and randomized clinical trials to
      increase survival beyond the disease burden of the target disease. The
      immunologic substrate for these non-specific protective effects have been
      ascertained to heterologous T cell effects on the one hand, and to priming of
      innate immunity on the other hand. The term 'trained immunity' has been proposed
      to describe these potentiating effects of vaccines on innate immune responses.
      This process can explain the rapid effects of BCG vaccination and has been
      suggested to be mediated by epigenetic programming of monocytes or macrophages.
      This novel concept has important implications for the possible use of vaccines,
      for vaccination policy and even for the design of novel immunotherapeutic
      approaches. 

PMID- 25573105
TI  - Sex-based differences in immune function and responses to vaccination.
AB  - Females typically develop higher antibody responses and experience more adverse
      reactions following vaccination than males. These differences are observed in
      response to diverse vaccines, including the bacillus Calmette-Guerin vaccine, the
      measles, mumps and rubella vaccine, the yellow fever virus vaccine and influenza
      vaccines. Sex differences in the responses to vaccines are observed across
      diverse age groups, ranging from infants to aged individuals. Biological as well
      as behavioral differences between the sexes are likely to contribute to
      differences in the outcome of vaccination between the sexes. Immunological,
      hormonal, genetic and microbiota differences between males and females may also
      affect the outcome of vaccination. Identifying ways to reduce adverse reactions
      in females and increase immune responses in males will be necessary to adequately
      protect both sexes against infectious diseases. 

PMID- 25573108
TI  - BCG-associated heterologous immunity, a historical perspective: experimental
      models and immunological mechanisms.
AB  - Randomized controlled trials indicate that bacille Calmette-Guerin (BCG) has
      beneficial heterologous ('non-specific') effects on mortality in high mortality
      settings. These findings have stimulated interest in understanding the
      immunological mechanisms underlying these effects in the hope of harnessing them
      to reduce all-cause mortality. This line of investigation is especially important
      in light of BCG being discontinued in some countries as the prevalence of TB
      falls. Stopping routine BCG in this situation may have the unintended consequence
      of depriving children of the beneficial immune modulating effects of this
      vaccine. BCG has been recognized as a potent immunomodulator for decades. This
      review details experimental studies involving BCG and any heterologous antigen
      that aimed to interrogate potential immunological mechanisms. To provide a
      historical perspective, the evidence is presented chronologically. The lines of
      immunological enquiry can be seen to mirror the evolution of our understanding of
      cell-mediated immunity and its components. As new clinical trials to investigate
      the heterologous effects of BCG are undertaken, an understanding of the history
      of BCG-induced immunity against heterologous antigens may provide information on
      immunological pathways worthy of further interrogation using modern immunological
      methods. 

PMID- 25573109
TI  - BCG-associated heterologous immunity, a historical perspective: intervention
      studies in animal models of infectious diseases.
AB  - The WHO Special Advisory Group of Experts (SAGE) review of the available
      epidemiological and trial evidence in humans concluded that bacillus Calmette
      Guerin (BCG) vaccination leads to beneficial heterologous ('non-specific')
      effects, specifically on all-cause mortality. Randomized controlled trials
      showing this beneficial effect suggest improved survival is the result of
      enhanced protection against infection. This paper reviews the available evidence
      for the attenuating effects of BCG vaccine on experimental infections in animal
      models, including protection from bacteria, viruses, parasites and fungi. The
      reviewed studies suggest that BCG activates multiple immune pathways and that the
      basis for BCG-associated heterologous immunity may vary by pathogen. Modern
      immunological and molecular methods, exemplified by 'vaccinomics', are well
      placed to further investigate the basis of BCG's heterologous effects using a
      systems biology approach.

PMID- 25573111
TI  - Nanoparticles modify dendritic cell homeostasis and induce non-specific effects
      on immunity to malaria.
AB  - BACKGROUND: Many current vaccines to a specific pathogen influence responses to
      other pathogens in a process called heterologous immunity. We propose that their
      particulate nature contributes to non-specific effects. Herein, we demonstrate
      polystyrene nanoparticles modulate dendritic cell (DC) homeostasis, thereby
      promoting a persistent enhanced state of immune readiness to a subsequent
      infectious challenge. METHODS: Particles (approximately 40 nm and 500 nm
      carboxylated polystyrene nanoparticles; PSNPs) alone or conjugated to a model
      antigen were injected in mice, and DCs in draining lymph nodes (dLNs) and bone
      marrow (BM) quantified by flow cytometry. BM cells were tested for capacity to
      generate DCs upon culture with granulocyte and macrophage colony stimulating
      factor. Mice were challenged with Plasmodium yoelli. Blood parasitaemias were
      monitored by GIEMSA. Sera was analyzed for antibodies by ELISA. RESULTS:
      Intradermal administration of 40 nm PSNPs induced anti-inflammatory cytokines,
      chemokines and growth factors, increased numbers and proportions of DCs in the
      dLN, and increased the capacity of BM to generate DCs. Consistent with these
      unexpected changes, 40 nm PSNPs pre-injected mice had enhanced ability to
      generate immunity to a subsequent malarial infection. CONCLUSIONS: Intradermal
      administration of 40 nm PSNPs modifies DC homeostasis, which may at least in part
      explain the observed beneficial heterologous effects of current particulate
      vaccines. Further nanotechnological developments may exploit such strategies to
      promote beneficial non-specific effects.

PMID- 25573112
TI  - Sex-differential and non-specific effects of routine vaccinations in a rural area
      with low vaccination coverage: an observational study from Senegal.
AB  - BACKGROUND: We examined the potential sex-differential and non-specific effects
      of bacille Calmette-Guerin (BCG), diphtheria-tetanus-pertussis (DTP) and measles
      vaccine (MV) in a rural area of Senegal. METHODS: The 4133 children born in the
      area between 1996 and 1999 were included in the study. Vaccinations were provided
      at three health centres. Vaccine information was collected through 3-monthly home
      visits. The survival analysis compared the effects of BCG and DTP according to
      the following sequence of vaccinations: BCG-first, BCG+DTP1-first, or DTP1-first.
      We compared DTP and MV between 9 and 24 months of age, as 9 months is the minimum
      age for MV. RESULTS: At 12 months the vaccination coverage was 44%, 46% and 9%,
      respectively, for BCG, DTP1 and MV. Most children received BCG+DTP1-first and
      this combination was associated with a significantly lower mortality rate ratio
      (MRR) of 0.69 (0.53-0.89) compared with unvaccinated children. There was no
      benefit for children receiving BCG-first or DTP1-first. The female-male MRR was
      0.79 (0.64-0.96) among unvaccinated children, but was significantly inversed with
      1.45 (1.00-2.10) for children receiving DTP vaccination (test of homogeneity,
      p=0.006). Children who had received DTP simultaneously with MV or DTP after MV
      had significantly higher mortality (MRR=2.59 [1.32-5.07]) compared with children
      having MV-only as their most recent vaccination. After 9 months, the female-male
      MRR was 0.61 (0.31-1.19) for measles-vaccinated children but remained 1.54 (1.03
      2.31) for DTP-vaccinated children who had not received MV (p=0.01). CONCLUSIONS:
      The sequence of routine vaccinations is important for the overall impact on child
      survival and these vaccines are associated with sex-differential effects.

PMID- 25573113
TI  - Molecular and functional diversity of yeast and fungal lipases: their role in
      biotechnology and cellular physiology.
AB  - Lipase catalyzes hydrolysis of fats in lipid water interphase and perform variety
      of biotransformation reactions under micro aqueous conditions. The major sources
      include microbial lipases; among these yeast and fungal lipases are of special
      interest because they can carry out various stereoselective reactions. These
      lipases are highly diverse and are categorized into three classes on the basis of
      oxyanion hole: GX, GGGX and Y. The detailed phylogenetic analysis showed that GX
      family is more diverse than GGGX and Y family. Sequence and structural
      comparisons revealed that lipases are conserved only in the signature sequence
      region. Their characteristic structural determinants viz. lid, binding pocket and
      oxyanion hole are hotspots for mutagenesis. Few examples are cited in this review
      to highlight the multidisciplinary approaches for designing novel enzyme variants
      with improved thermo stability and substrate specificity. In addition, we present
      a brief account on biotechnological applications of lipases. Lipases have also
      gained attention as virulence factors, therefore, we surveyed the role of lipases
      in yeast physiology related to colonization, adhesion, biofilm formation and
      pathogenesis. The new genomic era has opened numerous possibilities to
      genetically manipulate lipases for food, fuel and pharmaceuticals. 

PMID- 25573110
TI  - Vaccination and heterologous immunity: educating the immune system.
AB  - This review discusses three inter-related topics: (1) the immaturity of the
      neonatal and infant immune response; (2) heterologous immunity, where prior
      infection history with unrelated pathogens alters disease outcome resulting in
      either enhanced protective immunity or increased immunopathology to new
      infections, and (3) epidemiological human vaccine studies that demonstrate
      vaccines can have beneficial or detrimental effects on subsequent unrelated
      infections. The results from the epidemiological and heterologous immunity
      studies suggest that the immune system has tremendous plasticity and that each
      new infection or vaccine that an individual is exposed to during a lifetime will
      potentially alter the dynamics of their immune system. It also suggests that each
      new infection or vaccine that an infant receives is not only perturbing the
      immune system but is educating the immune system and laying down the foundation
      for all subsequent responses. This leads to the question, is there an optimum way
      to educate the immune system? Should this be taken into consideration in our
      vaccination protocols? 

PMID- 25573114
TI  - Ritual circumcision and risk of autism spectrum disorder in 0- to 9-year-old
      boys: national cohort study in Denmark.
AB  - OBJECTIVE: Based on converging observations in animal, clinical and ecological
      studies, we hypothesised a possible impact of ritual circumcision on the
      subsequent risk of autism spectrum disorder (ASD) in young boys. DESIGN:
      National, register-based cohort study. SETTING: Denmark. PARTICIPANTS: A total of
      342,877 boys born between 1994 and 2003 and followed in the age span 0-9 years
      between 1994 and 2013. MAIN OUTCOME MEASURES: Information about cohort members'
      ritual circumcisions, confounders and ASD outcomes, as well as two supplementary
      outcomes, hyperkinetic disorder and asthma, was obtained from national registers.
      Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin
      status were obtained using Cox proportional hazards regression analyses. RESULTS:
      With a total of 4986 ASD cases, our study showed that regardless of cultural
      background circumcised boys were more likely than intact boys to develop ASD
      before age 10 years (HR = 1.46; 95% CI: 1.11-1.93). Risk was particularly high
      for infantile autism before age five years (HR = 2.06; 95% CI: 1.36-3.13).
      Circumcised boys in non-Muslim families were also more likely to develop
      hyperkinetic disorder (HR = 1.81; 95% CI: 1.11-2.96). Associations with asthma
      were consistently inconspicuous (HR = 0.96; 95% CI: 0.84-1.10). CONCLUSIONS: We
      confirmed our hypothesis that boys who undergo ritual circumcision may run a
      greater risk of developing ASD. This finding, and the unexpected observation of
      an increased risk of hyperactivity disorder among circumcised boys in non-Muslim
      families, need attention, particularly because data limitations most likely
      rendered our HR estimates conservative. Considering the widespread practice of
      non-therapeutic circumcision in infancy and childhood around the world,
      confirmatory studies should be given priority.

PMID- 25573116
TI  - FlowSOM: Using self-organizing maps for visualization and interpretation of
      cytometry data.
AB  - The number of markers measured in both flow and mass cytometry keeps increasing
      steadily. Although this provides a wealth of information, it becomes infeasible
      to analyze these datasets manually. When using 2D scatter plots, the number of
      possible plots increases exponentially with the number of markers and therefore,
      relevant information that is present in the data might be missed. In this
      article, we introduce a new visualization technique, called FlowSOM, which
      analyzes Flow or mass cytometry data using a Self-Organizing Map. Using a two
      level clustering and star charts, our algorithm helps to obtain a clear overview
      of how all markers are behaving on all cells, and to detect subsets that might be
      missed otherwise. R code is available at https://github.com/SofieVG/FlowSOM and
      will be made available at Bioconductor.

PMID- 25573115
TI  - MicroRNA miR-466 inhibits Lymphangiogenesis by targeting prospero-related
      homeobox 1 in the alkali burn corneal injury model.
AB  - BACKGROUND: Lymphangiogenesis is one of the major causes of corneal graft
      rejection. Among the lymphangiogenic factors, vascular endothelial growth factor
      (VEGF)-C and -D are considered to be the most potent. Both bind to VEGF receptor
      3 (VEGFR3) to activate Prospero homeobox 1 (Prox1), a transcription factor
      essential for the development and maintenance of lymphatic vasculature. MicroRNAs
      (miRNAs) bind to the 3' untranslated regions (3' UTRs) of target genes in a
      sequence-specific manner and suppress gene expression. In the current study, we
      searched for miRNAs that target the pro-lymphangiogenic factor Prox1. RESULTS:
      Among the miRNAs predicted by the bioinformatic analysis to seed match with the
      3' UTR of Prox-1, we chose 3 (miR-466, miR-4305, and miR-4795-5p) for further
      investigation. Both the miR-466 and miR-4305 mimics, but not the miR-4795-5p
      mimic, significantly reduced the luciferase activity of the Prox-1 3' UTR
      reporter vector. In primary lymphatic endothelial cells (HDLEC), miR-466 mimic
      transfection suppressed Prox1 mRNA and protein expression, while miR-4305 mimic
      transfection did not. Experiments using mutated reporter constructs of the two
      possible seed match sites on the 3' UTR of Prox1 suggested that the target site 2
      directly bound miR-466. HDLEC transfected with the miR-466 mimic suppressed tube
      formation as compared to the scrambled control. Furthermore, HDLEC transfected
      with a miR-466 inhibitor showed enhanced tube formation as compared to control
      inhibitor transfected cells, and this inhibitory effect was counteracted by Prox1
      siRNA. The miR-466 mimic reduced angiogenesis and lymphangiogenesis resulting in
      clearer corneas in an cornea injury rat model compared to the scrambled control.
      CONCLUSIONS: Our data suggest that miR-446 may have a protective effect on
      transplanted corneas by suppressing Prox1 expression at the post-transcriptional
      level. The results of the current study may provide insights into the mechanisms
      of lymphangiogenesis resulting from corneal graft rejection and alkali-burn
      injuries, as well as into the development of new treatments for lymphangiogenic
      eye diseases.

PMID- 25573117
TI  - Immunohistochemical Characterization of Sympathetic Chain Ganglia (SChG) Neurons
      Supplying the Porcine mammary Gland.
AB  - The aim of this study was to investigate the chemical coding of mammary gland
      projecting SChG neurons using double-labelling immunohistochemistry. Earlier
      observation showed that after injection of the retrograde tracer fast blue (FB)
      into the second, right thoracic mamma, FB+ mammary gland-projecting neurons were
      found in Th1-3, Th9-14 and L1-4 right SChG. The greatest number of FB+ nerve cell
      bodies was observed in Th10 (approx. 843) and Th11 (approx. 567). Neurons
      projecting to the last right abdominal mamma were found in L1-4 SChG. The
      greatest number of FB+ neurons was observed in L2 (approx. 1200).
      Immunohistochemistry revealed that the vast majority of FB+ mammary-projecting
      neurons contained immunoreactivities to TH (96.97%) and/or DbetaH (95.92%). Many
      TH/DbetaH-positive neurons stained for SOM (41.5%) or NPY (33.2%), and less
      numerous nerve cells expressed VIP (16.9%). This observation strongly corresponds
      to the results of previous studies concerning the immunohistochemical
      characterization of nerve fibres supplying the porcine mammary gland. 

PMID- 25573118
TI  - Bayesian models trained with HTS data for predicting beta-haematin inhibition and
      in vitro antimalarial activity.
AB  - A large quantity of high throughput screening (HTS) data for antimalarial
      activity has become available in recent years. This includes both phenotypic and
      target-based activity. Realising the maximum value of these data remains a
      challenge. In this respect, methods that allow such data to be used for virtual
      screening maximise efficiency and reduce costs. In this study both in vitro
      antimalarial activity and inhibitory data for beta-haematin formation, largely
      obtained from publically available sources, has been used to develop Bayesian
      models for inhibitors of beta-haematin formation and in vitro antimalarial
      activity. These models were used to screen two in silico compound libraries. In
      the first, the 1510 U.S. Food and Drug Administration approved drugs available on
      PubChem were ranked from highest to lowest Bayesian score based on a training set
      of beta-haematin inhibiting compounds active against Plasmodium falciparum that
      did not include any of the clinical antimalarials or close analogues. The six
      known clinical antimalarials that inhibit beta-haematin formation were ranked in
      the top 2.1% of compounds. Furthermore, the in vitro antimalarial hit-rate for
      this prioritised set of compounds was found to be 81% in the case of the subset
      where activity data are available in PubChem. In the second, a library of about
      5000 commercially available compounds (Aldrich(CPR)) was virtually screened for
      ability to inhibit beta-haematin formation and then for in vitro antimalarial
      activity. A selection of 34 compounds was purchased and tested, of which 24 were
      predicted to be beta-haematin inhibitors. The hit rate for inhibition of beta
      haematin formation was found to be 25% and a third of these were active against
      P. falciparum, corresponding to enrichments estimated at about 25- and 140-fold
      relative to random screening, respectively. 

PMID- 25573119
TI  - Transformation of naltrexone into mesembrane and investigation of the binding
      properties of its intermediate derivatives to opioid receptors.
AB  - We transformed naltrexone (5) with the morphinan skeleton into mesembrane (4)
      belonging to the Sceletium alkaloids via key intermediate 6, characterized by a
      cis-fused hydroindole skeleton with a suspended phenyl ring fixed by an epoxy
      bridge. We then investigated the binding affinities of 4 and the key intermediate
      6 derivatives to the opioid receptors. Among the tested compounds, 15', with a
      cis-fused hydroindole core, bound to the three opioid receptor types with strong
      to moderate affinities. The observed differences of binding affinities among the
      tested compounds were reasonably explained by the conformational analyses of the
      compounds. The structure-activity relationship (SAR) of the tested compounds like
      15' with the hydroindole structure was completely different from the reported SAR
      of morphinan derivatives with the hydroisoquinoline skeleton. Compound 15' with a
      structure that differs from the morphinans represents a useful fundamental
      skeleton with a novel chemotype that may contribute to the development of new
      opioid ligands. 

PMID- 25573120
TI  - Anti-K formation is not associated with the storage time of transfused red blood
      cells.
AB  - BACKGROUND: The formation of red blood cell (RBC) antibodies could be enhanced by
      the presence of inflammation caused by prolonged RBC storage, as was shown in
      animal studies. The low occurrence (<10%) of K-antigen in most populations often
      enables identification of the K+ RBC unit that triggered anti-K formation and
      determination of its storage time. This study aims to quantify the association of
      anti-K formation with RBC storage time. STUDY DESIGN AND METHODS: K- patients who
      had not been previously transfused and received at least 1 K+ unit between
      January 2004 and August 2013 were identified. First, the influence of storage
      time of the K+ units was assessed as mean, maximum, and minimum storage times
      within one transfusion interval and at various cutoff points for old versus young
      blood (14, 18, and 21 days). Second, concomitantly transfused K- units were
      studied within different periods surrounding the K+ unit(s). RESULTS: Twenty
      three patients formed anti-K, while 274 patients did not. The adjusted relative
      risks of anti-K formation for mean, maximum, and minimum storage time (days)
      ranged from 1.01 to 1.03 (95% confidence interval, 0.96-1.08). When analyzing the
      association between only "younger" and only "older" K+ units at various cutoff
      points, no association was found. Similarly, no association was found between
      storage time of the concomitantly transfused K- units and anti-K formation.
      CONCLUSION: Within the range of storage times used in normal clinical practice in
      the Netherlands, no association could be found between RBC storage time and anti
      K formation.

PMID- 25573121
TI  - [The efficacy of antiviral therapy and drug resistance analysis among HIV/AIDS
      patients with heroin addiction in Guangxi Zhuang Autonomous Region].
AB  - OBJECTIVE: To investigate the impact of heroin for antiviral treatment, drug
      resistance, mutation types and frequency in HIV/AIDS patients in Guangxi Zhuang
      Autonomous Region. METHODS: HIV/AIDS patients were recruited in Methadone
      Maintenance Treatment Clinics, HIV/AIDS Clinic and HIV Voluntary Counseling and
      Testing Center Liuzhou and Baise city from April 2008 to October 2009. The
      patients were grouped by the situation of antiviral treatment and use of heroin.
      A total of 435 HIV/AIDS patients were recruited, among which 108 cases in
      antiviral treatment and heroin group, 93 cases in antiviral treatment and never
      using drug group, 105 cases in no antiviral treatment and using heroin group, 129
      cases in no antiviral treatment and never using drug group. The effect of
      antiviral treatment was evaluated by questionnaire survey, viral load measurement
      and CD4(+) T lymphocyte count. HIV-1 RNA from plasma was extracted, and then the
      pol genes were amplified and sequenced. The sequences were analyzed for HIV-1
      genotype drug-resistance. RESULTS: For the patients who received antiviral
      treatment, the viral load in heroin group was higher than that in never using
      drug group (lg (2.61 +/- 1.24) vs lg (2.08 +/- 0.80), t = 3.54, P < 0.05) , and
      the percentage of viral load lower than 1 000 copies/ml in heroin group was
      significantly less than that in never using drug group (63.9% vs 86.0%,chi(2) =
      12.76, P < 0.05). For the patients who received antiviral treatment, the
      difference has no significance in CD4(+) T lymphocyte count between heroin group
      and never using drug group ((337.92 +/- 181.66) vs (326.14 +/- 254.98), t = 0.38,
      P = 0.703). For the patients who didn't receive antiviral treatment, the
      difference also has no significance in CD4(+) T lymphocyte count between heroin
      group and never using drug group ((373.73 +/- 155.97) vs (337.53 +/- 209.26), t =
      1.47, P = 0.143). For the patients who received antiviral treatment, there was no
      difference in the percentage of the CD4(+) T lymphocyte count more than 350/ml
      between heroin group and never using drug group (48.1% vs 43.0%, chi(2) = 0.53, P
      = 0.466). 319 HIV-1 pol gene sequences were obtained. Among the patients who
      received antiviral treatment, the mutation frequency of M184V/I, T215Y/F, L210W
      and T69N/S in heroin abuser group were significantly higher than that in never
      using drug group (14.9% (11/74) vs 4.4% (3/68), 12.2% (9/74) vs 1.5% (1/68),
      12.2% (9/74) vs 1.5% (1/68) and 10.8% (8/74) vs 1.5% (1/68) respectively) (P <
      0.05). CONCLUSION: Using heroin may promote HIV replication, reducing the
      virological response to antiviral treatment and increasing the frequencies of
      drug resistance loci among HIV/AIDS patients.Heroin rehabilitation may benefit
      from the antiviral treatment and obtain better antiviral effect.

PMID- 25573122
TI  - [A study on syphilis and HSV-2 infection and related behaviors among female sex
      workers who take new types of drugs in Jiaozhou city].
AB  - OBJECTIVE: To explore the prevalence of syphilis and HSV-2 among female sex
      workers (FSWs) who use new types of drugs in Jiaozhou city. METHODS: Through
      convenient sampling, an anonymous questionnaire survey was conducted among female
      sex workers to collect demographic characteristics, new-type drugs abusing
      characteristics and related sexual behaviors from October to December, 2013.
      Blood specimens were drawn for serological tests of syphilis antibody and HSV-2
      antibody. Urine specimens of the subjects surveyed were collected to test for
      methamphetamine. Differences in demographic characteristics, new-type drug
      abusing characteristics, and sexual behaviours between drug-abusing FSWs and non
      drug-abusing FSWs were compared by t-test and chi(2)-test. RESULTS: A total of
      460 FSWs were recruited in this study, and 105 FSWs admitted their drug abuse
      history. Among the 341 urine specimens confirmed to be methamphetamine positive,
      there were 3 FSWs claimed that they never abuse new-type drugs. The rate of new
      type drug abuse was 23.5% (108/460). A total of 71.4% (75/105) of the new drug
      abusing FSWs started using drugs under 25 years old. The main reasons for drug
      abuse were clients request (24, 22.9%), making more money (23, 21.9%) and
      companion temptations (22, 21.0%). Totally, 41.9% of them (44/105) took drugs
      with 4-5 persons, 32.4% (34/105) had sex with 2-3 men after taking drugs, and
      60.2% of new-type drug-abusing FSWs (65/108) used condoms in the latest
      commercial intercourse, while only 7.4% FSWs (8/108) used condoms every time
      during their commercial sex activities in the recent month. Compared with FSWs
      having no drug abuse behavior, drug-abusing FSWs had higher single proportion
      (73.2% (79/108) vs 63.6% (224/352), chi(2) = 8.64, P < 0.05), lower condom use
      rate in the recent month (7.4% (8/108) vs 22.7% (80/352), chi(2) = 12.53, P <
      0.01) and higher pregnancy rate in the recent 6 months (24.1% (26/108) vs 8.8%
      (31/352), chi(2) = 17.74, P < 0.01) and most of them come from the middle and
      high-level entertainmens (78.7% (85/108) vs 65.1% (229/352), chi(2) = 13.09, P <
      0.01). Among the new-type drug-abusing FSWs, the prevalence rates of syphilis and
      HSV-2 were 12.0% (13/108) and 55.6% (60/108) , respectively. A total of 33 FSWs
      claimed that they were diagnosed with STDs in the recent year (30.6%) . The rates
      of syphilis(12.0% (13/108) vs 4.0% (14/352), chi(2) = 9.72, P < 0.01), HSV
      2(55.6% (60/108) vs 39.2% (138/352), chi(2) = 9.01, P < 0.01) and diagnosed STDs
      (30.6% (33/108) vs 17.9% (63/352), chi(2) = 8.02, P < 0.01) among the drug
      abusing FSWs were significantly higher than those of non-drug-abusing FSWs.
      CONCLUSION: There is a higher proportion of new-type drug abuse among the FSWs in
      Jiaozhou, with significantly higher prevalence rates of syphilis and HSV-2
      infection, compared with non-new types of drug abusing FSWs. Prevalent risk
      sexual behaviors and ignorance of new-types drugs' harm were seen among them.

PMID- 25573123
TI  - [Survey of Hepatitis B infection and vaccination status among drug users in
      Xi'an].
AB  - OBJECTIVE: To explore seroepidemiological status and vaccine coverage of
      hepatitis B among drug users in Xi'an. METHODS: 545 drug users in the Xi'an
      Compulsory Detoxification Center were asked to answer questionnaire and provide
      blood sample (3-5 ml) for test of HBsAg, anti-HBc and anti-HBs from March to June
      2013. Totally, 545 subjects were surveyed and tested. All of them effectively
      completed the survey. RESULTS: The positive rates of HBsAg, anti-HBc and anti-HBs
      were 29.4% (160/545), 60.0% (327/545) and 56.1% (306/545), respectively. Eighty
      five subjects (15.6%) were negative for all of the three markers. The prevalence
      of HBsAg and anti-HBc among injection drug users were 40.0% (94/235) and 65.6%
      (154/235), which was significantly higher than non- injection drug users' (21.6%
      (52/241), 58.5% (141/241)) and mixed non-injection and injection drug users
      ((20.3% (14/69), 46.4% (32/69)) (chi(2) = 23.518 and 9.017, respectively, P <
      0.05) . The HBsAg positive rate (30.6% (153/500)) of subjects with more than once
      per day of drug using within one year was significantly higher than those who
      used drugs for 2-3 times per week (15.6% (7/45)) (chi(2) = 4.51, P < 0.05). Only
      11.7% (64/545) of drug users had a clear history of hepatitis B vaccination. The
      vaccination rate of subjects (3.5% (5/141)) with primary education or below was
      significantly lower than those with high school (16.3% (45/276)) (chi(2) = 26.61,
      P < 0.05). The vaccination rate of subjects (7.8% (12/153)) over 45 years old was
      significantly lower than that of subjects below 30 years old (15.9% (21/132)) and
      30-44 years old (11.9% (31/260)) (chi(2) = 30.36, P < 0.05). The vaccinees had a
      significantly higher positive rate of anti-HBs (73.4% (47/64)) than those who
      without vaccination (53.8% (259/481)) (chi(2) = 8.81, P = 0.003), but the
      positive rates of HBsAg (16.7% (11/64)) were lower than those who without
      vaccination (31.0% (149/481)) (chi(2) = 23.52 and 9.02, respectively;P > 0.05).
      CONCLUSION: The HBV infection status among drug users in Xi'an was in serious
      condition, while a low vaccination rate was also discovered among them.

PMID- 25573124
TI  - [The situation of neglect state among elementary and high school students aged 6
      17 years in rural areas of two western provinces of China].
AB  - OBJECTIVE: To understand the neglect situation of elementary and high school
      students aged 6-17 years in western rural areas of China. METHODS: Using multi
      stage stratified cluster sampling method, 4 131 students were recruited from 26
      rural elementary and high schools of 7 districts in Shanxi province and Chongqing
      from September 2012 to April 2013. The investigation was conducted based on 'The
      Development of Neglect Evaluation Norms and Influence Factors for Primary and
      Middle School Students' in rural areas of China. SAS 9.21 software was used for
      analyzing neglect rate and neglect degree for groups of age, sex and neglect
      types (including neglect of physical, emotional, medical, educational, safety and
      social). RESULTS: The total neglect rate and degree were 55.50% (1 943/3 501) and
      49.96 +/- 9.67; the neglect rates for males and females were 56.78% (1 018/1 793)
      and 54.16% (925/1 708) (P = 0.119); the neglect degrees were 50.08 +/- 9.31 and
      49.83 +/- 10.02 (P = 0.479), respectively. The girls' medical neglect rate
      (18.25%, 348/1 907) was significantly higher than that in boys (14.72%, 294/1
      997) (P < 0.01); the boys' neglect degrees of physical, educational and social
      neglect (50.05 +/- 10.46, 49.99 +/- 10.81, 57.63 +/- 14.63) were significantly
      higher than that in girls (49.34 +/- 10.70, 49.07 +/- 11.30, 56.37 +/- 14.80) (P
      < 0.05). The total neglect rates of 6-8, 9-11, 12-14 and 15-17 groups were 44.48%
      (310/697), 60.40% (511/846), 60.89% (601/987) and 53.66% (521/971) (P < 0.01),
      and the total neglect degrees among these groups were 46.89 +/- 8.57, 51.88 +/-
      9.25, 51.88 +/- 9.25 and 51.72 +/- 8.89 (P < 0.01), respectively. Except the
      neglect rates of medical and social neglect, significant differences were found
      in other three neglect rates and neglect degrees. The rates of social, emotional
      and safety neglect in 9-11 group were higher than that in other groups (28.39%
      (264/930), 26.41% (239/905), 20.35% (187/919)). The 12-14 group has the highest
      educational neglect rate(29.41%, 317/1 078). While the physical and emotional
      neglect degrees in 12-14 and 15-17 group were higher than that in other groups(12
      14 group: 51.59 +/- 10.02, 53.43 +/- 12.02, 15-17 group: 51.96 +/- 9.80, 52.61 +/
      11.59). The social, safety, educational and medical neglect degrees were the
      highest in 6-8, 9-11, 12-14 and 15-17 group (60.91 +/- 13.13, 48.29 +/- 11.34,
      52.43 +/- 10.55, 51.15 +/- 17.25), respectively. The neglect rates and neglect
      degrees were significantly higher in minorities(68.88% (374/543) and 52.91 +/-
      9.14) than those in Han population (53.04% (1 569/2 958), 49.44 +/- 9.67)(P <
      0.01 in both indexes); and the neglect rates and neglect degrees were
      significantly higher in children with siblings group (58.20% (1 504/2 584), 50.58
      +/- 9.54) than those the in one-child group (47.87% (439/917), 48.27 +/- 9.80) (P
      < 0.01 in both indexes); and the neglect rates and neglect degrees were
      significantly higher in left-hand students (61.65% (1 101/1 786), 51.41 +/- 9.51)
      than those in living-with-parents students(49.10% (842/1 715), 48.56 +/- 9.61) (P
      < 0.01 in both indexes). CONCLUSION: The children neglect situation is serious in
      western rural areas, close attention from families, schools and the society is in
      urgent need.

PMID- 25573125
TI  - [Analysis on the incidence and influencing factors of psychological violence
      among college students in Guangzhou in 2010].
AB  - OBJECTIVE: To study the incidence and influencing factors of psychological
      violence among college students in Guangzhou in 2010. METHODS: Convenience
      sampling method was used and 2 200 college students from 61 classes of three
      universities in Guangzhou were interviewed with self-designed questionnaire about
      the incidence and influencing factors of the psychological violence in 2010. The
      valid sample was 2 060. Chi-square test and multinomial logistic regression were
      used to assess the incidence and influencing factors of the psychological
      violence between different genders. RESULTS: A total of 66.3% (1 365/2 060)
      college students reported having experienced at least one kind of psychological
      violence during the past 12 months, either as a perpetrator or as a victim. The
      proportion of psychological violence among males (72.3%, 775/1 072) was
      significantly higher than that in females (59.7%, 590/988)(chi(2) = 36.39, P <
      0.05). The incidence of perpetration only, victimization only, and both
      perpetration and victimization of psychological violence were 16.1% (331/2 060),
      8.9% (184/2 060) and 41.3% (850/2 060), respectively. The incidence of
      victimization only in females was 10.4% (103/988), which was significantly higher
      than that in males (7.6%, 81/1 072) (chi(2) = 5.20, P < 0.05). The incidence of
      both perpetration and victimization in males was 47.3% (507/1 072), which was
      significantly higher than that in females (34.7%, 343/988) (chi(2) = 33.56, P <
      0.05). In males, the multinomial logistic regression showed the risk factors for
      perpetration only was having harmful behavior habits (OR = 1.90). For
      victimization only, the risk factors were with siblings (OR = 2.42) and prior
      mistreatment by teachers from primary to senior high school (OR = 1.78). For both
      perpetration and victimization, the risk factors were with siblings (OR = 1.88),
      having harmful behavior habits (OR = 1.98), bad family economic conditions
      (difficult OR = 1.99, general OR = 1.67) and prior mistreatment by teachers from
      primary to senior high school(OR = 2.07). In females, the risk factors for
      perpetration only were self-claimed shortage of monthly living expenses(OR =
      2.14) or just enough (OR = 2.26), having harmful behavior habits (OR = 1.69) (all
      P values<0.05) . For victimization only, the risk factors were bad family
      economic conditions (difficult OR = 6.67, 15 persons; general OR = 3.81), bullied
      by others before university(OR = 2.05). For both perpetration and victimization,
      the risk factors were self-claimed shortage of monthly living expenses (OR =
      1.81), bad family economic conditions (OR = 2.43), disharmonious relations
      between parents (OR = 1.76), physical punishment by parents (OR = 1.66), bullied
      by others before university (OR = 2.14) and prior mistreatment by teachers from
      primary to senior high school(OR = 1.73). Having a religious faith was the
      protective factor (OR = 0.38) (all P values<0.05). CONCLUSION: The incidence of
      psychological violence among college students is very serious in Guangzhou in
      2010. And the influencing factors of it between different genders are different.
      Females are affected by a wider ranges of factors than males, and are more
      influenced by family and parents.

PMID- 25573126
TI  - [Association between the level of fasting blood glucose over 35-year-old and
      carotid intima-media thickness in Han, Uygur and Kazak population from Xinjiang
      Uygur Autonomous Region from 2007 to 2010].
AB  - OBJECTIVE: To analyze the relationship between different levels of fasting blood
      glucose over 35-year old and carotid intima-media thickness (IMT) in Han, Uygur
      and Kazak adult population from Xinjiang Uygur Autonomous Region. METHODS: From
      October 2007 to April 2010, the present study was performed in 13 935 inhabitants
      among Han, Uygur and Kazak adult population of aged 35 years old and over by
      multi-stage stratified cluster random sampling principles from 7 regions in
      Xinjiang Uygur Autonomous and we excluded the IMT over 0.9 millimeter, long-term
      out and the floating population. All subjects were measured fasting blood glucose
      and IMT values of carotid artery. The subjects were divided into three groups
      according to different fasting blood glucose levels: normal, impaired fasting
      glucose (IFG) and diabetes mellitus (DM) and we used the analysis of variance to
      compare the differences among groups of IMT. Multiple linear regression model was
      used to explore factors of carotid IMT. RESULTS: The IMT of males of Han, Uygur
      and Kazak were (0.81 +/- 0.29), (0.71 +/- 0.27) and (0.79 +/- 0.21) mm
      respectively, the differences were significant (F = 88.50, P < 0.05) . The IMT in
      DM group ((0.82 +/- 0.29) mm) was significantly higher than the normal ((0.77 +/-
      0.26) mm) and the IFG groups ((0.79 +/- 0.27) mm) (F = 7.49, P < 0.05). The IMT
      of females of Han, Uygur and Kazak were (0.72 +/- 0.27), (0.63 +/- 0.25) and
      (0.77 +/- 0.22) mm, respectively, the differences were significant (F = 173.93, P
      < 0.05) . The IMT in DM group ((0.75 +/- 0.29) mm) and the IFG groups ((0.74 +/-
      0.26) mm) were significantly higher than the normal group ((0.70 +/- 0.25) mm) (F
      = 10.46, P < 0.05). Multivariate regression analysis showed that diastolic blood
      pressure (beta = 0.101, P < 0.01) , total cholesterol (beta = 0.056, P < 0.05)
      and fasting blood glucose (beta = 0.023, P = 0.009) were independent risk factors
      of IMT. CONCLUSION: The level of fasting blood glucose was an independent
      influence factor of carotid IMT and had a positive correlation in Han, Uygur and
      Kazak population of Xinjiang Autonomous Region.

PMID- 25573127
TI  - [Enumeration and antimicrobial resistance of Campylobacter species from retail
      chicken carcasses].
AB  - OBJECTIVE: To determine Campylobacter contamination level and antimicrobial
      resistance patterns from chicken carcasses in supermarkets and farmer's markets
      of 9 districts in Beijing. METHODS: From August 2012 to July 2013, whole chicken
      carcasses (n = 240) were collected from 27 supermarkets and 18 farmer's markets
      of nine districts in Beijing. The level of Campylobacter contamination was
      enumerated by plate counting method using the modified Karmali and modified
      Preston agar. Presumptive Campylobacter isolates were identified and
      characterized by gram stain, agglumination test and a multiplex PCR method. The
      level of Campylobacter contamination was calculated following the USDA/FSIS
      Campylobacter enumeration method. Selected 151 Campylobacter isolates were
      further characterized by minimal inhibitory concentrations(MICs) of eight
      antimicrobials. RESULTS: A total of 26.3% (63/240) of the retail whole chicken
      carcasses were contaminated by Campylobacter and 151 Campylobacter isolates were
      recovered, including 85 Campylobacter jejuni isolates and 66 Campylobacter coli
      isolates. The P25, P50, P75 of Campylobacter contamination concentration were
      7.5, 45.0 and 350.0 CFU/g, respectively. The antimicrobial resistance rate of C.
      jejuni and C. coli were as the following: azithromycin(AZI, 13% (11/85), 82%
      (54/85)), chloramphenicol (CHL, 33% (28/85), 42% (28/85)), ciprofloxacin (CIP,
      95% (81/85), 100% (85/85)), doxycycline (DOX, 38% (32/85), 80% (53/85)),
      erythromycin (ERY, 12% (10/85), 82% (54/85)), gentamicin (GEN, 25% (21/85), 68%
      (45/85)), tetracycline (TET, 67% (57/85), 73% (62/85)), all isolates were
      susceptible to meropenem (MEP). The multi-drug resistance ratio of C. jejuni (55%
      (47/85) )was significantly lower than that (86% (57/66) )of C. coli (chi(2) =
      16.70, P < 0.01). Among 151 Campylobacter isolates, 21 antimicrobial resistance
      patterns were identified, including 20 patterns among C. jejuni isolates and 10
      patterns among C.coli isolates. Among C.jejuni isolates, CIP-DOX-TET was dominant
      (22% (19/85)), followed by CIP-TET (14% (12/85)), CHL-CIP-TET(9% (8/85)) and CHL
      CIP-GEN (7% (6/85)). Among C.coli isolates,AZI-CHL-CIP-DOX-ERY-GEN-TET (35%
      (23/66)) was the dominant, followed by AZI-CIP-DOX-ERY-GEN-TET (21% (14/66) )and
      AZI-CIP-DOX-ERY-TET(15% (10/66)). CONCLUSION: Our findings showed a high
      prevalence and concentration of Campylobacter contamination in retail chicken
      carcasses of nine districts in Beijing, especially the on-site slaughtered
      chicken from the farmer's markets. The resistance levels of these recovered
      Campylobacter isolates were serious.

PMID- 25573128
TI  - [Detection rate analysis on neurological sign of workers exposed to different
      concentrations of carbon disulfide].
AB  - OBJECTIVE: To study the effects of exposed to different concentrations of carbon
      disulfide on neurological signs of workers. METHODS: Collection the information
      of concentration of carbon disulfide in the workplace or workers individuals
      exposed of a chemical fiber industry from 2004 to 2011, a total of 3 537 workers
      exposed to carbon disulfide were detected muscle strength and muscle tone, knee
      reflex, Achilles tendon reflex, trembling limbs, sensory function, and three
      chatter. Chi-square test was used for statistical analysis on abnormal
      neurological signs of workers. RESULTS: Eight hours time-weighted average
      concentration range of workers exposed to carbon disulfide in this chemical fiber
      industry was 0.2-41.0 mg/m(3), geometric mean was 2.38 mg/m(3). Concentration of
      carbon disulfide exposure of 1 771 workers was from 0.2 to 2.5 mg/m3( <= 2.5
      mg/m(3)), 642 workers was 2.6-4.8 mg/m(3) (< 5.0 mg/m(3)), other 1 051 workers
      was from 5.1 to 41.0 mg/m(3) ( > 5.0 mg/m(3)) in all subjects. The different
      detection rates of knee reflex were 3.0% (31/1 045), 3.7% (21/574), 4.8%
      (16/331), 3.3% (10/305), 5.9% (11/187), 6.7% (68/1 022), the different detection
      rates of Achilles tendon reflex were 2.2% (23/1 045), 3.7% (21/574), 2.7%
      (9/331), 2.3% (7/305), 2.1% (4/187), 5.6% (57/1 022), the different detection
      rates of sensory dysfunction were 0.4% (4/1 045), 0.5% (3/574), 0.6% (2/331),
      0.0% (0/305), 2.1% (4/187), 1.7% (17/1 022) in different cumulative amount of
      contact groups ( <= 10.0, 10.1-20.0, 20.1-30.0, 30.1-40.0, 40.1-50.0, >50.0
      mg/m(3) per year), and the differences were statistically significant (chi(2) =
      19.53, 21.27 and 15.89, all P values were <0.01) . Stratified according to age
      and gender, in addition to the <= 25 years group the difference of detection rate
      analysis on Achilles tendon reflex was statistically significant in the different
      concentration group (the ratio of on Achilles tendon reflex in the different
      groups of concentration of carbon disulfide exposure of 2.5, 2.6-5.0, >= 5.0
      mg/m(3) were 0.4% (2/511), 1.0% (1/98), 2.1% (7/327), chi(2) = 5.59, P = 0.045) ,
      the difference of detection rate analysis on neurological sign was not
      statistically significant in the different concentration group on the rest of the
      age and gender groups (P > 0.05). CONCLUSION: Within the concentration range of
      the object of study contact actual, different concentrations of carbon disulfide
      in addition to individual neurological signs of individual ages influential, it
      has no significant effect on the various signs of nervous system of workers of
      most age and gender groups, expect the age below the 25 years old group.

PMID- 25573129
TI  - [Analysis on the association of single nucleotide polymorphism in the promoter
      region of pre-miR-320b-2 with coronary heart disease risk and factors influencing
      circulating microRNA-320b level].
AB  - OBJECTIVE: To investigate the effects of rs10916581, a common single nucleotide
      polymorphism (SNP) located in the promoter region of pre-miR-320b-2, on coronary
      heart disease (CHD) risk and circulating microRNA-320b (miR-320b) level. To
      explore potential factors influencing circulating miR-320b level. METHODS:
      Rs10916581 was genotyped in a case-control study with 1 507 CHD cases and 1 379
      age- and sex-frequency-matched controls. The cases were consecutively recruited
      from 3 hospitals (Tongji Hospital, Union Hospital, and Wugang Hospital) in Wuhan
      city (Hubei, China) between May 2004 and October 2009 and all the controls
      resided in Wuhan communities. A subgroup of 174 CHD cases and 181 non-diabetes
      controls without acute infection were randomly selected and their circulating miR
      320b levels were detected using quantitative reverse transcriptase polymerase
      chain reaction assays. The association of rs10916581 with CHD susceptibility was
      analyzed with multivariable logistic regression model. Generalized linear
      regression model was used to explore the associations of rs10916581 and some
      other factors with circulating miR-320b level. RESULTS: In single-factor logistic
      regression analysis, no association was found between rs10916581 and CHD risk.
      After adjustment for age, sex, BMI, smoking status, hypertension, diabetes, total
      triglyceride, total cholesterol/high density lipoprotein (TC/HDL-C), the result
      did not materially alter(compared with CC genotype, the OR (95%CI) of CHR in the
      subjects carried CT, TT, CT+TT genotypes were 0.94 (0.76-1.15), 0.99 (0.74-1.33)
      and 0.95 (0.78-1.16) ). No significant interactions were observed between the
      conventional risk factors of CHD (age, gender, smoking status, BMI, hypertension,
      diabetes, CHD family history) and rs10916581 on CHD risk (P > 0.05). Rs10916581
      showed no significant association with circulating miR-320b level in cases,
      controls or total population (beta(95%CI) was -0.028 (-0.495-0.440), 0.250 (
      0.226-0.727) and 0.134 (-0.218-0.486) respectively, P > 0.05). However,
      circulating miR-320b level was negatively associated with BMI (beta (95%CI) was 
      0.140 (-0.261--0.020), P = 0.022) while positively associated with TC/HDL(beta
      (95%CI) was 0.620 (0.261-0.979), P = 0.001) in cases, and in total population,
      its circulating level tended to be lower in diabetes or hypertension patients
      (beta(95%CI) was -1.025 (-1.696--0.354) and -0.594 (-1.138--0.049) respectively,
      P = 0.003, 0.033 respectively) and was positively associated with TC/HDL-C
      (beta(95%CI) was 0.108 (0.027-0.190), P = 0.009). CONCLUSION: The common SNP
      (rs10916581) in the promoter region of pre-miR-320b-2 might have little
      contribution to the CHD predisposition in Chinese Han population, and it might
      not affect circulating miR-320b level. Conventional CHD risk factors (BMI, TC/HDL
      C, hypertension and diabetes) might have effects on its circulating level.

PMID- 25573130
TI  - [An association study between gene polymorphism of the key enzyme's folacin
      metabolism pathway and plasmatic homocysteine levels in fertile woman].
AB  - OBJECTIVE: The effect of the gene polymorphism for the key enzyme's folacin
      metabolism pathway on plasmatic homocysteine (Hcy) levels in fertile woman was
      observed. METHODS: The subjects were from Shaoxing City, Jiangsu province in
      2012, the selection criteria for the women of childbearing age were between 20-45
      years old, with an average age of 28.2 (95%CI:27.8-28.6) years old. Sample
      collection continued uninterrupted lasted seven days, a total of 535 samples were
      collected, venous blood with EDTA addition or sodium citrate to anticoagulant.
      After separation, the blood cells and blood plasma were cryopreserved. DNA was
      extracted using spin column method. All the samples were selected for the gene
      polymorphism testing of the key enzyme's on folate metabolism and monitoring of
      plasmatic Hcy level. RESULTS: Eight single nucleotide polymorphism (SNP) sites of
      methylenetetrahydrofolate reductase gene (MTHFR) , methionine synthase gene (MS)
      , synthetic methionine reductase gene (MSR) and cystathionine beta synthase gene
      (CBS) were detected. It was found the genotype AA of the SNP sites-rs1801131
      would result higher plasmatic Hcy levels (8.99 umol/L) than the genotypes CC
      (7.81 umol/L) and CA(8.38 umol/L) (P < 0.01) . Similarly, the genotype TT of the
      SNP sites-rs1801133 was significantly responded to the increasing of Hcy levels
      (11.10 umol/L) than the genotype CC (8.15 umol/L) and CT (8.45 umol/L), (P <
      0.01) . The two sites of genotype combination of AA-TT could also result in the
      significant increase of Hcy levels (11.02 umol/L) than other combined genotypes
      (genotypes CC-CC, CA-CC, CA-CT, AA-CC, AA-CT), especially the genotype CC-CC. And
      the risk factor was 1.41 (95CI:1.20-1.66) times over the genotype CC-CC.
      CONCLUSION: The gene mutations of two SNP sites rs1801131 and rs1801133 in MTHFR
      would increase Hcy levels.

PMID- 25573131
TI  - [Study of synergistic effect of free fatty acid and iron on the establishment of
      nonalcoholic fatty liver disease model].
AB  - OBJECTIVE: To establish nonalcoholic fatty liver disease (NAFLD) model induced by
      free fatty acid (FFA) and iron, and to explore the synergistic effect of FFA and
      Fe(2+) on the pathogenesis of NAFLD and mechanisms. METHODS: Human liver
      carcinoma cell HepG2 was respectively treated with 0.250, 0.500, 1.000 mmol/L
      oleic acid, 0.500 mmol/L oleic acid+0.125 mmol/L Fe(2+), 0.500 mmol/L oleic
      acid+0.250 mmol/L Fe(2+), and 0.500 mmol/L oleic acid+0.500 mmol/L Fe(2+). Human
      liver carcinoma cell HepG2 was normally cultured in the control group. Lipid
      accumulation of cells were observed by oil red O staining and the determination
      of the triglyceride (TG) contents by GPO-PAP, then the expression of key genes
      involved in fatty acid beta-oxidation (fatty acyl CoA synthetase-1 (ACSL-1),
      carnitine acyl transferase 1 (CPT-1a), fatty acid synthetase (FAS)) was
      determined using RT-PCR. The differences of TG content and ACSL-1, CPT-1a, FAS,
      mRNA relative value were analyzed among different groups. RESULTS: The results of
      oil red O staining indicated that the contents of lipid droplets were obviously
      elevated with the increase of Fe(2+) concentration in human liver carcinoma cell
      HepG2 treated with 0.500 mmol/L oleic acid and different concentrations of
      Fe(2+). The TG contents of HepG2 cell in control group, 0.250, 0.500, 1.000
      mmol/L oleic acid groups, 0.500 mmol/L oleic acid+0.125 mmol/L Fe(2+) group,
      0.500 mmol/L oleic acid+0.250 mmol/L Fe(2+) group, 0.500 mmol/L oleic acid+0.500
      mmol/L Fe(2+) group respectively were (90.0 +/- 1.6), (131.7 +/- 5.4), (153.7 +/-
      3.0), (254.1 +/- 4.0), (164.5 +/- 6.0), (180.1 +/- 7.7), (235.6 +/- 4.5) nmol/mg
      (F = 396.00, P < 0.05). The expression levels of ACSL-1 mRNA in 0.500 mmol/L
      oleic acid group, 0.500 mmol/L oleic acid+0.125 mmol/L Fe(2+) group, 0.500 mmol/L
      oleic acid +0.250 mmol/L Fe(2+) group, 0.500 mmol/L oleic acid +0.500 mmol/L
      Fe(2+) group respectively were (0.94 +/- 0.02), (0.89 +/- 0.04), (0.85 +/- 0.02),
      (0.74 +/- 0.04) (F = 50.00, P < 0.05); the mRNA levels of CPT-1a were (0.89 +/-
      0.03), (0.79 +/- 0.05), (0.67 +/- 0.04), (0.51 +/- 0.05) (F = 79.00, P < 0.05);
      the mRNA levels of FAS were (1.31 +/- 0.05) , (1.44 +/- 0.03), (1.51 +/- 0.05),
      (1.56 +/- 0.06 ) (F = 79.70, P < 0.05). CONCLUSION: The NAFLD liver cell model
      could be established by oleic acid and Fe(2+) in HepG2 cells. FFA and iron might
      be involved in the pathogenesis of NAFLD through the intervention of fatty acid
      beta-oxidation.

PMID- 25573132
TI  - Correct recognition and management of anaphylaxis: not much change over a decade.
AB  - BACKGROUND: Anaphylaxis is increasing in incidence. This potentially fatal
      condition requires immediate intramuscular adrenaline as a vital part of early
      treatment. A 2002 survey of UK Senior House Officers showed a lack of knowledge
      regarding the recognition and management of anaphylaxis. Since then major changes
      in medical education and updated national guidelines have aimed to ensure that
      doctors can recognise and treat anaphylaxis appropriately. OBJECTIVES: To
      determine current knowledge concerning the recognition and management of
      anaphylaxis among junior doctors compared to their predecessors. METHODS: Using
      the same methodology as in 2002, we asked 68 Foundation doctors to read five
      clinical scenarios potentially suggesting anaphylaxis and indicate how they would
      respond to each case. Their results were compared to those of Senior House
      Officers in 2002. RESULTS: 68 of 107 (64%) junior doctors completed the
      questionnaire. All recognised the need for adrenaline in anaphylaxis, but only
      74% selected the correct intramuscular route, and 34% the correct route and dose.
      82% of junior doctors would inappropriately give adrenaline to the patient who
      had inhaled a foreign body (case 2). A higher percentage of the 2013 cohort
      indicated the correct route and dose of adrenaline in anaphylaxis than their 2002
      colleagues. However, a greater percentage also selected adrenaline treatment
      inappropriately in non-anaphylactic case scenarios. CONCLUSIONS: Despite updated
      guidelines, junior doctors continue to have poor knowledge about the recognition
      and management of anaphylaxis, with some still considering inappropriate
      intravenous adrenaline. More effort should be given to the recognition of
      anaphylaxis in early medical training.

PMID- 25573133
TI  - Adrenaline in anaphylaxis: overtreatment in theory, undertreatment in reality.

PMID- 25573134
TI  - A new classification of cochleovestibular malformations and implications for
      predicting speech perception ability after cochlear implantation.
AB  - OBJECTIVES: The aims of this study were to introduce a new classification of
      cochleovestibular malformation (CVM) and to investigate how well this
      classification can predict speech perception ability after cochlear implantation
      in children with CVM. METHODS: Fifty-nine children with CVM who had used a
      cochlear implant for more than 3 years were included. CVM was classified into 4
      subtypes based on the morphology of the cochlea and the modiolus on temporal bone
      computed tomography (TBCT): normal cochlea and normal modiolus (type A, n = 16),
      malformed cochlea and partial modiolus (type B, n = 31), malformed cochlea and no
      modiolus (type C, n = 6), and no cochlea and no modiolus (type D, n = 6). Speech
      perception test scores were compared between the subtypes of CVM using analysis
      of covariance with post hoc Bonferroni test. Univariate and multivariate
      regression analyses were used to identify the significant predictors of the
      speech perception test scores. RESULTS: The speech perception test scores after
      implantation were significantly better in children with CVM type A or type B than
      in children with CVM type C or type D. The test scores did not differ
      significantly between the implanted children with CVM type A or type B and those
      without CVM. In univariate regression analysis, the type of CVM was a significant
      predictor of the speech perception test scores in implanted children with CVM.
      Multivariate regression analysis revealed that the age at cochlear implantation,
      cochlear nerve size and preimplantation speech perception test scores were
      significant predictors of the postimplantation speech perception test scores. The
      chance of cochlear nerve deficiency increased progressively from CVM type A to
      type D. CONCLUSION: The new classification of CVM based on the morphology of the
      cochlea and the modiolus is simple and easy to use, and correlated well with
      postimplantation speech perception ability and cochlear nerve status. This simple
      classification of CVM using TBCT with cochlear nerve assessment by magnetic
      resonance imaging is helpful in the preoperative evaluation of children with CVM.

PMID- 25573135
TI  - Chronic effects of tributyltin on multiple biomarkers responses in juvenile
      common carp, Cyprinus carpio.
AB  - In this study, the chronic toxic effects of tributyltin (TBT), an antifouling
      paints commonly present in surface and ground water, on morphological indices,
      reactive oxygen species (ROS) generation, and ATPase activity and heat shock
      protein (Hsp) 70 protein in tissues (liver, gill, and white muscle) of common
      carp were investigated. Fish were exposed at sublethal concentrations of TBT (75
      ng/L, 0.75 MUg/L, and 7.5 MUg/L) for 60 days. When compared with the control,
      there was significant lower condition factor in fish exposed at the higher
      concentration of TBT. ROS levels in three tissues increased significantly at
      higher TBT concentrations (0.75 and 7.5 MUg/L). The hepatic antioxidant enzymes
      (total antioxidative capacity and superoxide dismutase) activities were induced
      at higher concentrations (0.75 MUg/L) of TBT. When compared with the hepatic
      antioxidant enzymes activities in fish exposed to 0.75 MUg/L of TBT, there was a
      decreasing trend in those exposed to TBT with a concentration of 7.5 MUg/L.
      However, all the antioxidant enzymes activities were significantly inhibited in
      gill and muscle of fish exposed to higher TBT concentrations (0.75 and 7.5
      MUg/L). Moreover, there was significant lower Na-K-ATPase in three tissues after
      long-term exposure to higher concentration of TBT, but a significant higher Hsp70
      protein levels was observed. In short, environmental concentrations of TBT could
      not induce obvious impacts on fish, but long-term exposure to higher
      concentrations of TBT could affect seriously the health status of fish. (c) 2015
      Wiley Periodicals, Inc. Environ Toxicol 31: 937-944, 2016. 

PMID- 25573136
TI  - Religious differences in self-rated health among US Jews: findings from five
      urban population surveys.
AB  - Research findings on religion and health among Jews are in relatively short
      supply. While recent studies report on the health of Israelis and the mental
      health of Jews in the USA, little information exists on the physical health of US
      Jews, especially from population surveys. In this study, data are analyzed from
      five urban surveys of Jews conducted since 2000: two surveys from New York (N =
      4,533; N = 5,993) and one apiece from Chicago (N = 1,993), Philadelphia (N =
      1,217), and Boston (N = 1,766). A strategy of two-way ANCOVA with interaction was
      used to test for differences in self-rated health across five categories of
      Jewish religious affiliation (secular, Reform, Reconstructionist, Conservative,
      Orthodox) and four categories of synagogue attendance (from never to at least
      weekly). Findings, adjusted for age and effects of other covariates, reveal that
      affiliated and synagogue-attending Jews report moderately better health than
      secular and non-attending Jews.

PMID- 25573137
TI  - Simultaneous transcatheter aortic valve replacement and endovascular repair for
      critical aortic stenosis and large abdominal aortic aneurysm.
AB  - A 75-year-old man with severe aortic stenosis, severe chronic obstructive
      pulmonary disease, NYHA class III heart failure and a large abdominal aortic
      aneurysm underwent concurrent transfemoral transcatheter aortic valve replacement
      (TF-TAVR) and endovascular aneurysm repair (EVAR). An Edwards Sapien device was
      implanted with resolution of hemodynamics. EVAR was performed using an Endurant
      bifurcated stent graft system. We describe the procedure technique,
      periprocedural management and one year outcome. To the authors' best knowledge,
      this is the first case of simultaneous TF-TAVR and EVAR published in North
      America. 

PMID- 25573138
TI  - Resection of metachronous adrenal metastasis after liver resection and
      transplantation for hepatocellular carcinoma.
AB  - BACKGROUND: This study analyzed the patient survival outcomes following the
      resection of hepatocellular carcinoma (HCC) metachronous adrenal metastasis (MAM)
      in patients who had undergone liver resection or liver transplantation (LT).
      METHODS: Clinical results were analyzed retrospectively in 26 patients with MAM
      HCC who underwent adrenalectomy. RESULTS: The mean interval between initial
      surgery and adrenalectomy was significantly shorter in the resection group than
      in the LT group (18.3 +/- 14.4 vs. 42.6 +/- 13.8 months, p < 0.001). Of 19
      resected patients, four had adrenal metastases on the right side, 12 on the left
      side and three bilaterally, with a mean tumor diameter of 3.6 +/- 1.5 cm. Ten of
      these patients underwent open surgery and nine underwent laparoscopic surgery;
      all patients experienced recurrences within 18 months and 20.3% survived 5 years
      after adrenalectomy. Of 7 patients who underwent LT, four had adrenal metastases
      on the right side and three on the left side, with a mean tumor diameter of 3.4
      +/- 1.8 cm. Six of these patients underwent open surgery and one underwent
      laparoscopic surgery. Five-year recurrence and patient survival rates after
      adrenalectomy were 28.6 and 85.7%, respectively. CONCLUSIONS: Adrenalectomy is
      indicated in patients with isolated MAM-HCC. Comparisons with other locoregional
      treatment modalities and multicenter studies with additional patients are needed
      to validate the role of adrenalectomy.

PMID- 25573140
TI  - Design and enantioselective synthesis of Cashmeran odorants by using "enol
      catalysis".
AB  - Novel Cashmeran odorants were designed by molecular modeling. Their short
      syntheses involve a novel asymmetric Bronsted acid catalyzed Michael addition of
      unactivated alpha-substituted ketones. This key transformation was realized by
      utilizing a new type of enol activation catalysis and affords different cyclic
      ketones bearing alpha-quaternary stereocenters in good to excellent yields and
      with high enantioselectivity. Subsequent McMurry coupling and Saegusa-Ito
      oxidation furnished the enantiopure target odorants, one enantiomer of which
      indeed possesses the typical olfactory aspects of Cashmeran. 

PMID- 25573139
TI  - Application of the one-minute preceptor technique by novice teachers in the gross
      anatomy laboratory.
AB  - The one-minute preceptor (OMP) was originally developed in the ambulatory care
      setting as a time-efficient teaching technique for learner-centered clinical
      training. There are also possible advantages of using the OMP in the gross
      anatomy laboratory. However, in a previous study it was found that providing
      training to experienced gross anatomy teachers in the use of the OMP did not
      result in improvement in students' perceptions of their learning, probably
      because of the fact that the experienced teachers had already developed their own
      pedagogical approaches. In the current study, we examined the effects of training
      novice teachers with about four years of gross anatomy teaching experience, in
      the use of the OMP in the gross anatomy laboratory, by surveying students to
      collect their views on their learning experiences, by observing the teachers'
      teaching behaviors before and after they were trained in OMP, and then by
      interviewing them. More students reported a better learning experience in the
      session after the teachers had been trained in the OMP than reported worse, in
      eight out of the nine items related to their learning experiences. The novice
      teachers were receptive to the OMP. After the OMP training, the novice teachers
      were observed to engage more in getting commitments from the students and in
      reinforcing what the students have done right, two of the five OMP microskills.
      They considered the OMP to be very useful for their development as anatomy
      teachers.

PMID- 25573141
TI  - Prevention of deformational plagiocephaly in hospitalized infants using a new
      orthotic device.
AB  - OBJECTIVE: To measure the feasibility, safety, and efficacy of the cranial cup
      device in a sample of hospitalized infants at risk for deformational
      plagiocephaly (DP). DESIGN: A multisite, stratified, and randomized single
      blinded study. SETTING: Neonatal intensive care units (NICU) from three urban and
      one suburban hospital participated. PARTICIPANTS: Subjects included 62 infants
      with lengths of stay >= 14 days. METHODS: Nurses caring for infants in study
      group 1 used the moldable positioner. In study group 2, nurses rotated the
      moldable positioner and cranial cup devices using the cranial cup for a target
      goal of 12 hours/day. Both study groups received routine position changes.
      Outcome measures included hours of device use (feasibility), cardiorespiratory
      and emesis events (safety), and cranial measurements obtained at discharge
      (efficacy) by one of four, licensed orthotists who were blinded to the study.
      RESULTS: A total of 35 infants were randomized to study group 1 (moldable
      positioner) and 27 infants to study group 2 (moldable positioner and cranial
      cup). The median hours per day on the cranial cup was 10.7 (range 4.5-15.3).
      Emesis and cardiorespiratory events were equally distributed for the moldable
      positioner and cranial cup devices in study group 2. At discharge, more infants
      in study group 1 (46%, n = 16) exhibited abnormal cranial measurements than those
      in study group 2 (19%, n = 5) (p = .03). CONCLUSION: Rotating the cranial cup
      with the moldable positioner provides a feasible, safe, and potentially
      efficacious therapy for prevention of DP.

PMID- 25573142
TI  - Cholesterol oxidase with high catalytic activity from Pseudomonas aeruginosa:
      Screening, molecular genetic analysis, expression and characterization.
AB  - An extracellular cholesterol oxidase producer, Pseudomonas aeruginosa strain
      PA157, was isolated by a screening method to detect 6beta-hydroperoxycholest-4-en
      3-one-forming cholesterol oxidase. On the basis of a putative cholesterol oxidase
      gene sequence in the genome sequence data of P. aeruginosa strain PAO1, the
      cholesterol oxidase gene from strain PA157 was cloned. The mature form of the
      enzyme was overexpressed in Escherichia coli cells. The overexpressed enzyme
      formed inclusion bodies in recombinant E. coli cells grown at 20  degrees C and
      30  degrees C. A soluble and active PA157 enzyme was obtained when the
      recombinant cells were grown at 10  degrees C. The purified enzyme was stable at
      pH 5.5 to 10 and was most active at pH 7.5-8.0, showing optimal activity at pH
      7.0 and 70  degrees C. The enzyme retained about 90% of its activity after
      incubation for 30 min at 70  degrees C. The enzyme oxidized 3beta-hydroxysteroids
      such as cholesterol, beta-cholestanol, and beta-sitosterol at high rates. The Km
      value and Vmax value for the cholesterol were 92.6 MUM and 15.9 MUmol/min/mg of
      protein, respectively. The Vmax value of the enzyme was higher than those of
      commercially available cholesterol oxidases. This is the first report to
      characterize a cholesterol oxidase from P. aeruginosa.

PMID- 25573143
TI  - N-terminal pro-B-type natriuretic peptide and the risk of stroke and transient
      ischaemic attack: the Rotterdam Study.
AB  - BACKGROUND AND PURPOSE: Amino-terminal pro-B-type natriuretic peptide (NT-proBNP)
      is a predictor of heart disease. It has also been related to stroke, but its
      association with transient ischaemic attacks (TIAs) is unclear. Moreover, it is
      unknown how clinical heart disease influences this relation. Within the
      prospective population-based Rotterdam Study, the association of NT-proBNP with
      stroke and TIA was examined and the role of heart disease on this association was
      investigated. METHODS: NT-proBNP was measured in 1997-2001 in 5611 participants
      (mean age 68.7 years; 57.7% women) without a history of stroke, TIA or heart
      failure. Follow-up for stroke and TIA finished in 2012. Models were adjusted for
      age and cardiovascular risk factors, and were stratified by sex. RESULTS: During
      22 058 person-years 195 men suffered a stroke and 118 a TIA. During 31 825 person
      years 230 women suffered a stroke and 187 a TIA. Higher NT-proBNP was associated
      with a higher risk of stroke in men [hazard ratio (HR) per SD increase 1.50; 95%
      confidence interval (CI) 1.29-1.76] and in women (HR 1.24; 95% CI 1.05-1.46).
      Associations with TIA were only present in women (HR 1.51; 95% CI 1.26-1.82) but
      not in men (HR 1.02; 95% CI 0.83-1.26). Excluding persons with a history of
      clinical coronary heart disease, heart failure or atrial fibrillation and
      censoring for clinical heart disease during follow-up did not change the
      associations. CONCLUSIONS: Higher NT-proBNP is associated with incident stroke in
      men and women and with incident TIA only in women. These associations are
      independent of clinical heart disease preceding cerebrovascular disease.

PMID- 25573144
TI  - Electrical conductivity of p-type BiOCl nanosheets.
AB  - High quality BiOCl nanosheets were fabricated using facile, room temperature
      hydrolysis of Bi(NO3)3 and HCl. The resulting nanosheets had dimensions of 500 nm
      with the exposed {001} facet. The band gap of the nanosheets was found to be 3.34
      eV with conduction and valence band edges at -3.63 eV and -6.97 eV with respect
      to vacuum, respectively. The electrical conductivity of drop-cast BiOCl
      nanosheets was measured between aluminum patterned electrodes as a function of
      temperature and oxygen partial pressure (pO2). The activation energy for
      conduction in BiOCl was found to be 862 meV in the temperature range of 300-425 K
      and below 1000 mbar. The electrical conductivity varied with pO2, indicating
      sigma ? pO2(1/4.05) and sigma ? pO2(1/32) for low and sub atmospheric pressures,
      respectively. A prototypical device for low temperature (425 K) O2 sensing was
      demonstrated. 

PMID- 25573146
TI  - Intraoral versus extraoral measurement of the height of the interproximal contact
      area in maxillary anterior teeth.
AB  - OBJECTIVES: This study aimed to clinically quantify the apicoincisal height of
      the upper interproximal areas directly in patients' mouths compared to
      measurements on stone models. SUBJECTS AND METHODS: One hundred and fifty
      participants (75 females and 75 males, age range 20-45 years) were recruited for
      this study. A digital caliper was used to measure the anterior maxillary
      interproximal contact areas directly in patients' mouths and on stone models. The
      digital caliper accuracy was up to 0.01. The Statistical Package for Social
      Sciences software (SPSS, version 19.0, Chicago, Ill., USA) was used for
      statistical analysis. Statistical significance was based on probability values
      <0.05. RESULTS: The intraoral measurement of proximal contacts as well as the
      measurement on stone models showed that the dimensions of interproximal contacts
      on both sides of each tooth were significantly different (p < 0.001) and that the
      dimension of the mesial contact point was larger than that of the distal contact
      point of each tooth. The largest contact point was the one between the central
      incisors (direct intraoral measurement = 2.9-6.49 mm; model measurement = 3.31
      6.91 mm). On the other hand, the contact point between the canine and first
      premolar was the smallest on both sides of the arch (0.63-2.52 mm intraorally,
      0.98-2.88 mm on models). The intraoral measurement of contact points was more
      accurate than model measurements, and the differences were statistically
      significant (p < 0.001). CONCLUSIONS: The clinical evaluation of contact point
      dimensions using a digital caliper was more precise than measuring contact points
      on stone models; hence, it is a viable, quick and adequate method to be used
      routinely.

PMID- 25573145
TI  - Computational identification of multi-omic correlates of anticancer therapeutic
      response.
AB  - BACKGROUND: A challenge in precision medicine is the transformation of genomic
      data into knowledge that can be used to stratify patients into treatment groups
      based on predicted clinical response. Although clinical trials remain the only
      way to truly measure drug toxicities and effectiveness, as a scientific community
      we lack the resources to clinically assess all drugs presently under development.
      Therefore, an effective preclinical model system that enables prediction of
      anticancer drug response could significantly speed the broader adoption of
      personalized medicine. RESULTS: Three large-scale pharmacogenomic studies have
      screened anticancer compounds in greater than 1000 distinct human cancer cell
      lines. We combined these datasets to generate and validate multi-omic predictors
      of drug response. We compared drug response signatures built using a penalized
      linear regression model and two non-linear machine learning techniques, random
      forest and support vector machine. The precision and robustness of each drug
      response signature was assessed using cross-validation across three independent
      datasets. Fifteen drugs were common among the datasets. We validated prediction
      signatures for eleven out of fifteen tested drugs (17-AAG, AZD0530, AZD6244,
      Erlotinib, Lapatinib, Nultin-3, Paclitaxel, PD0325901, PD0332991, PF02341066, and
      PLX4720). CONCLUSIONS: Multi-omic predictors of drug response can be generated
      and validated for many drugs. Specifically, the random forest algorithm generated
      more precise and robust prediction signatures when compared to support vector
      machines and the more commonly used elastic net regression. The resulting drug
      response signatures can be used to stratify patients into treatment groups based
      on their individual tumor biology, with two major benefits: speeding the process
      of bringing preclinical drugs to market, and the repurposing and repositioning of
      existing anticancer therapies.

PMID- 25573148
TI  - Screening for miRNAs and their potential targets in response to TGF-beta1 based
      on miRNA microarray and comparative proteomics analyses in a mouse GC-1 spg germ
      cell line.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a member of the TGF-beta
      superfamily that performs a number of cellular functions and shows differential
      activity at different testicular developmental stages. In the present study, we
      investigated the effects of exogenous TGF-beta1 on global microRNA (miRNA or miR)
      expression profiles by miRNA microarray analysis and the alterations in protein
      profiles by two-dimensional gel electrophoresis and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) in a
      mouse GC-1 spg germ cell line. A total of 24 differentially expressed miRNAs,
      including 7 upregulated and 17 downregulated miRNAs were identified. The results
      obtained by the RT-qPCR analysis of 10 selected differentially expressed miRNAs
      were in accordance with those obtained by miRNA microarray analysis. In addition,
      11 differentially expressed proteins, including 3 upregulated and 8 downregulated
      proteins were identified through MS-based comparative proteomics analysis.
      Bioinformatics analysis predicted that peptidyl-prolyl isomerase A (PPIA) and
      nucleoside diphosphate kinase B (NDKB) are targets of miR-149 and miR-199a-3p,
      respectively in response to the stimulation of mouse GC-1 spg germ cells with TGF
      beta1. RT-qPCR revealed that the expression levels of these miRNAs showed an
      opposite trend in response to stimulation with TGF-beta1. In conclusion, we
      identified some important miRNAs and proteins as possible targets involved in TGF
      beta1 signaling. Our data suggest the existence of a TGF-beta1-miR-149-PPIA or
      TGF-beta1-miR-199a-3p-NDKB pathway in GC-1 spg cells. Further studies are
      warranted to ascertain the role of these miRNAs in spermatogenesis.

PMID- 25573149
TI  - Cost-effectiveness of alternative strategies for interferon-gamma release assays
      and tuberculin skin test in tuberculous uveitis.
AB  - BACKGROUND: Although tuberculous uveitis remains a major cause of ocular
      morbidity in the developing world, there is no consensus on which diagnostic test
      or testing strategy is the most cost effective. In this study we carried out a
      cost-effectiveness analysis to determine the most cost-effective diagnostic test
      strategy. METHODS: In this prospective study, we recruited 102 patients from
      Singapore National Eye Centre with signs suggestive of tuberculous uveitis. Using
      prospective data from this cohort and from published meta-analyses, we modelled
      the incremental cost effectiveness of the following strategies: tuberculin skin
      test (TST) only; interferon-gamma release assay (IGRA) only; IGRA following a
      positive TST result; and dual-test strategy, conducting TST and IGRA at
      presentation. Incremental cost-effectiveness ratios (ICERs) were calculated for
      each strategy and analysed using a willingness-to-pay threshold of $50,000 per
      quality-adjusted life year (QALY) gained. RESULTS: In our population, the least
      cost effective was the IGRA-only strategy. The dual-test strategy was the most
      cost effective, with an improvement of 0.017 QALY at an incremental cost of $190
      relative to the TST-only strategy (ICER $11,500); while the TST-only strategy was
      more cost effective than the third strategy, using IGRA following a positive TST
      result (ICER $3610). This remained consistent while varying the costs of IGRA and
      TST, the incidence of tuberculosis and tuberculous uveitis, as well as the
      diagnostic accuracy of IGRA and TST found in previous studies in various
      populations. CONCLUSIONS: The dual-test strategy (performing TST and IGRA at
      presentation) was the most cost effective strategy for the diagnosis of
      tuberculous uveitis in our population.

PMID- 25573150
TI  - Swept-source optical coherence tomography assessment of iris-trabecular contact
      after phacoemulsification with or without goniosynechialysis in eyes with primary
      angle closure glaucoma.
AB  - AIMS: To compare the change in iris-trabecular contact (ITC) area using swept
      source optical coherence tomography (SS-OCT) in eyes with primary angle closure
      glaucoma (PACG) and cataract that underwent phacoemulsification (PE) with
      intraocular lens implantation alone compared with PE with goniosynechialysis
      (GSL). METHODS: One eye of 22 patients with PACG with peripheral anterior
      synechiae (PAS) detected by indentation gonioscopy was randomised into two groups
      (PE alone (n=11) and PE+GSL (n=11)). The anterior chamber angles were evaluated
      by SS-OCT under dark conditions before and 12 months after surgery using the
      three-dimensional angle analysis scan protocol that simultaneously obtains 128
      cross-sectional radial scans across the anterior chamber at equal intervals
      (every 1.4 degrees ). The ITC area, defined as the area of extent of the
      circumferential contact of peripheral iris to the angle wall, was computed
      automatically by SS-OCT after an observer marked the scleral spurs of all 128
      scans of each eye. RESULTS: The majority of the 22 subjects were women (77.3%)
      and the mean+/-SD age was 67.3+/-5.8 years. The ITC area was significantly
      reduced in the PE+GSL group compared with the PE alone group (10.2 mm2 vs. 4.6
      mm2, beta=0.54, p=0.03) after adjusting for age, gender, intraocular pressure,
      extent of PAS and pupil diameter before surgery. Smaller iris volume at baseline
      was associated with greater ITC area reduction by PE+GSL (beta=-0.728, p=0.03).
      CONCLUSIONS: Eyes that undergo PE+GSL surgery have a greater reduction in
      circumferential ITC area than eyes that undergo PE alone.

PMID- 25573151
TI  - Gaucher-related synucleinopathies: the examination of sporadic neurodegeneration
      from a rare (disease) angle.
AB  - Gaucher disease, the most common lysosomal storage disease, is caused by a
      recessively inherited deficiency in glucocerebrosidase and subsequent
      accumulation of toxic lipid substrates. Heterozygous mutations in the lysosomal
      glucocerebrosidase gene (GBA1) have recently been recognized as the highest
      genetic risk factor for the development of alpha-synuclein aggregation disorders
      ("synucleinopathies"), including Parkinson's disease (PD) and dementia with Lewy
      bodies (DLB). Despite the wealth of experimental, clinical and genetic evidence
      that supports the association between mutant genotypes and synucleinopathy risk,
      the precise mechanisms by which GBA1 mutations lead to PD and DLB remain unclear.
      Decreased glucocerebrosidase activity has been demonstrated to promote alpha
      synuclein misprocessing. Furthermore, aberrant alpha-synuclein species have been
      reported to downregulate glucocerebrosidase activity, which further contributes
      to disease progression. In this review, we summarize the recent findings that
      highlight the complexity of this pathogenetic link and how several pathways that
      connect glucocerebrosidase insufficiency with alpha-synuclein misprocessing have
      emerged as potential therapeutic targets. From a translational perspective, we
      discuss how various therapeutic approaches to lysosomal dysfunction have been
      explored for the treatment of GBA1-related synucleinopathies, and potentially,
      for non-GBA1-associated neurodegenerative diseases. In summary, the link between
      GBA1 and synucleinopathies has become the paradigm of how the study of a rare
      lysosomal disease can transform the understanding of the etiopathology, and
      hopefully the treatment, of a more prevalent and multifactorial disorder. 

PMID- 25573147
TI  - Metabolite profiling and cardiovascular event risk: a prospective study of 3
      population-based cohorts.
AB  - BACKGROUND: High-throughput profiling of circulating metabolites may improve
      cardiovascular risk prediction over established risk factors. METHODS AND
      RESULTS: We applied quantitative nuclear magnetic resonance metabolomics to
      identify the biomarkers for incident cardiovascular disease during long-term
      follow-up. Biomarker discovery was conducted in the National Finnish FINRISK
      study (n=7256; 800 events). Replication and incremental risk prediction was
      assessed in the Southall and Brent Revisited (SABRE) study (n=2622; 573 events)
      and British Women's Health and Heart Study (n=3563; 368 events). In targeted
      analyses of 68 lipids and metabolites, 33 measures were associated with incident
      cardiovascular events at P<0.0007 after adjusting for age, sex, blood pressure,
      smoking, diabetes mellitus, and medication. When further adjusting for routine
      lipids, 4 metabolites were associated with future cardiovascular events in meta
      analyses: higher serum phenylalanine (hazard ratio per standard deviation, 1.18;
      95% confidence interval, 1.12-1.24; P=4*10(-10)) and monounsaturated fatty acid
      levels (1.17; 1.11-1.24; P=1*10(-8)) were associated with increased
      cardiovascular risk, while higher omega-6 fatty acids (0.89; 0.84-0.94; P=6*10(
      5)) and docosahexaenoic acid levels (0.90; 0.86-0.95; P=5*10(-5)) were associated
      with lower risk. A risk score incorporating these 4 biomarkers was derived in
      FINRISK. Risk prediction estimates were more accurate in the 2 validation cohorts
      (relative integrated discrimination improvement, 8.8% and 4.3%), albeit
      discrimination was not enhanced. Risk classification was particularly improved
      for persons in the 5% to 10% risk range (net reclassification, 27.1% and 15.5%).
      Biomarker associations were further corroborated with mass spectrometry in
      FINRISK (n=671) and the Framingham Offspring Study (n=2289). CONCLUSIONS:
      Metabolite profiling in large prospective cohorts identified phenylalanine,
      monounsaturated fatty acids, and polyunsaturated fatty acids as biomarkers for
      cardiovascular risk. This study substantiates the value of high-throughput
      metabolomics for biomarker discovery and improved risk assessment.

PMID- 25573153
TI  - Long-Term Maintenance of Inhibition Training Effects in Older Adults: 1- and 3
      Year Follow-Up.
AB  - OBJECTIVES: The aim of this study is to examine the long-term maintenance of
      training benefits in inhibition, as measured with the Stroop task, in older
      adults over 1- and 3-year periods. METHODS: Participants from an original 6
      session Stroop training study (Wilkinson & Yang, 2012 [Wilkinson, A. J., & Yang,
      L. (2012). Plasticity of inhibition in older adults: Retest practice and transfer
      effects. Psychology and Aging, 27, 606-615. doi:10.1037/a0025926]) were invited
      to come back to the lab to complete a single session of the Stroop task at 2
      different time points. Thirty-three older adults returned for the 1-year follow
      up session, and 26 of them returned for the 3-year follow-up session. RESULTS:
      The results revealed maintenance of the training-induced inhibition gains at both
      follow-up sessions. Furthermore, performance at the 2 follow-up sessions was
      better (i.e., reduced Stroop ratio interference score) than baseline level.
      DISCUSSION: The findings demonstrate the durability of inhibition training gains
      in older adults for up to a 3-year period. These results further extend the
      literature on long-term maintenance of cognitive training benefits in older
      adults by examining the durability of training effects in inhibition, an
      important executive function, and by covering a substantial maintenance period
      (i.e., up to 3 years).

PMID- 25573152
TI  - "My Parent is so Stubborn!"-Perceptions of Aging Parents' Persistence,
      Insistence, and Resistance.
AB  - OBJECTIVE: Aging parents may respond to advice or help with daily problems from
      their grown children by insisting, resisting, or persisting in their ways or
      opinions, behaviors which are commonly viewed as stubbornness. Research has not
      examined how frequently such behaviors occur and what factors are associated with
      these behaviors. METHODS: Middle-aged adults and parents (N = 189 dyads) reported
      the prevalence of parental behaviors attributed to stubbornness. Utilizing
      hierarchical linear regression and multilevel modeling this exploratory study
      examined the association of parent stubbornness with individual and relationship
      based characteristics and concordance in reports within dyads. RESULTS: Over 77%
      of children and 66% of parents reported parents acting in ways attributed to
      stubbornness at least sometimes. Children reported higher levels of parental
      stubbornness than parents self-reported. Children's perceptions of occurrence
      were related to parent disability and relationship characteristics, while
      parents' self-reports were associated with their own personalities. Discrepancies
      in reports between parents and children were associated with child and parent
      characteristics. DISCUSSION: This novel exploration demonstrated that individual
      and relationship-based factors are linked to the perceived expression of
      stubbornness by parents and that there is discordance in perceptions within
      families. Findings suggest a need for intervention to increase understanding
      within families.

PMID- 25573154
TI  - Abnormal stress responsivity in a rodent developmental disruption model of
      schizophrenia.

PMID- 25573155
TI  - Dopamine Receptor Blockade Modulates the Rewarding and Aversive Properties of
      Nicotine via Dissociable Neuronal Activity Patterns in the Nucleus Accumbens.

PMID- 25573158
TI  - Involvement of RalB in the effect of geranylgeranyltransferase I on glioma cell
      migration and invasion.
AB  - PURPOSE: The present study aimed at investigating the role and potential
      mechanism of geranylgeranyltransferase I (GGTase-I) on glioma cell migration and
      invasion. METHODS: Wound-healing assay and transwell assay were performed to
      study whether GGTase-I and Ras-like GTPase B (RalB) have effect on glioma cell
      migration and invasion. RESULTS: We found that knockdown of GGTase-I or RalB both
      significantly decreased the migratory and invasive abilities of glioma cells.
      GGTase-I down-regulation suppressed RalB membrane association. Moreover, down
      regulation of RalB partially abolished the effect of GGTbeta over-expression
      induced glioma cell migration and invasion increase. CONCLUSIONS: These findings
      suggest that RalB might be one of the targets for facilitating the invasive
      phenotype of malignant gliomas induced by GGTase-I.

PMID- 25573156
TI  - Acetate supplementation as a means of inducing glioblastoma stem-like cell growth
      arrest.
AB  - Glioblastoma (GBM), the most common primary adult malignant brain tumor, is
      associated with a poor prognosis due, in part, to tumor recurrence mediated by
      chemotherapy and radiation resistant glioma stem-like cells (GSCs). The metabolic
      and epigenetic state of GSCs differs from their non-GSC counterparts, with GSCs
      exhibiting greater glycolytic metabolism and global hypoacetylation. However,
      little attention has been focused on the potential use of acetate supplementation
      as a therapeutic approach. N-acetyl-l-aspartate (NAA), the primary storage form
      of brain acetate, and aspartoacylase (ASPA), the enzyme responsible for NAA
      catalysis, are significantly reduced in GBM tumors. We recently demonstrated that
      NAA supplementation is not an appropriate therapeutic approach since it increases
      GSC proliferation and pursued an alternative acetate source. The FDA approved
      food additive Triacetin (glyceryl triacetate, GTA) has been safely used for
      acetate supplementation therapy in Canavan disease, a leukodystrophy due to ASPA
      mutation. This study characterized the effects of GTA on the proliferation and
      differentiation of six primary GBM-derived GSCs relative to established U87 and
      U251 GBM cell lines, normal human cerebral cortical astrocytes, and murine neural
      stem cells. GTA reduced proliferation of GSCs greater than established GBM lines.
      Moreover, GTA reduced growth of the more aggressive mesenchymal GSCs greater than
      proneural GSCs. Although sodium acetate induced a dose-dependent reduction of GSC
      growth, it also reduced cell viability. GTA-mediated growth inhibition was not
      associated with differentiation, but increased protein acetylation. These data
      suggest that GTA-mediated acetate supplementation is a novel therapeutic strategy
      to inhibit GSC growth.

PMID- 25573160
TI  - Special issue on 11th FACS meeting.

PMID- 25573159
TI  - Gender-related alterations in plasma adrenomedullin level and its correlation
      with body weight gain.
AB  - Plasma levels of adrenomedullin (AM), a bioactive peptide produced in adipose
      tissue, have been shown to be higher in obese patients than in non-obese
      patients, but little is known about gender differences in plasma AM levels. The
      aims of this study were to clarify gender-related alterations in plasma AM levels
      and to examine the body weight (BW) gain-plasma AM relationship in the general
      population. We measured plasma AM levels of 346 local residents (62.0+/-8.9
      years, mean+/-s.d.) in the Kiyotake area, Japan, who underwent a regular health
      check-up, by a specific fluorescence immunoassay. Plasma AM levels in the female
      residents were lower than that in the males, and multiple regression analysis
      revealed a possible gender difference in plasma AM. The AM levels were
      significantly correlated with BMI or waist circumference in women, but such a
      relationship was not seen in men. When the subjects were divided into two groups
      by results of a questionnaire about BW gain of 10 kg or more since the age of 20
      years, the plasma AM level of women with BW gain ?10 kg was significantly higher
      than that in those without BW gain, although no difference was noted between the
      men with and without BW gain. In conclusion, possible gender differences were
      noted in the plasma AM levels and in the BW gain-plasma AM relationship in the
      general population. The plasma AM levels in the female residents without BW gain
      seem partly attributable to the lower AM of women. 

PMID- 25573161
TI  - Restriction fragment length polymorphism analysis of rotavirus VP7-encoding gene
      from humans and animals of Northeast India: a relative study of Indian and global
      isolates.
AB  - A restriction fragment length polymorphism (RFLP) assay was developed to examine
      the genetic relationship between 67 (29 Indian, 38 global) rotavirus isolates of
      human, bovine and porcine neonates. The assay involved direct digestion of RT-PCR
      amplified VP7 cDNAs with three restriction enzymes (VspI, HaeIII, NlaIV)
      independently. Forty-eight RFLP patterns were identified for all 67 strains, and
      of these 20 patterns were associated with Indian isolates. A correlation between
      the restriction patterns and G type was apparent through deduction of enzyme
      restriction sites from known sequences. Major G serotypes (G1, G2, G6, G8) with a
      few mixed types could be differentiated where there was a positive assortment of
      intrinsic serotypes from multiple host origin, and certain single or combined
      enzyme profiles were highly dominant in the population. Significant genetic
      variations were established between global and Indian isolates and none of the
      RFLP patterns were shared between them. These data suggest that the Indian wild
      type rotavirus population is distinguishable based on the VP7 gene, and co
      circulation of distinct strains in different hosts is foremost, indicating the
      possible likelihood of inter-species transmission. 

PMID- 25573162
TI  - Heteromers of amyloid precursor protein in cerebrospinal fluid.
AB  - BACKGROUND: Soluble fragments of the amyloid precursor protein (APP) generated by
      alpha- and beta-secretases, sAPPalpha and sAPPbeta, have been postulated as
      promising new cerebrospinal fluid (CSF) biomarkers for the clinical diagnosis of
      Alzheimer's disease (AD). However, the capacity of these soluble proteins to
      assemble has not been explored and could be relevant. Our aim is to characterize
      possible sAPP oligomers that could contribute to the quantification of sAPPalpha
      and sAPPbeta in CSF by ELISA, as well as to characterize the possible presence of
      soluble full-length APP (sAPPf). RESULTS: We employed co-immunoprecipitation,
      native polyacrylamide gel electrophoresis and ultracentrifugation in sucrose
      density gradients to characterize sAPP oligomers in CSF. We have characterized
      the presence of sAPPf in CSF from NDC and AD subjects and demonstrated that all
      forms, including sAPPalpha and sAPPbeta, are capable of assembling into
      heteromers, which differ from brain APP membrane-dimers. We measured sAPPf,
      sAPPalpha and sAPPbeta by ELISA in CSF samples from AD (n = 13) and non-disease
      subjects (NDC, n = 13) before and after immunoprecipitation with antibodies
      against the C-terminal APP or against sAPPbeta. We demonstrated that these sAPP
      heteromers participate in the quantification of sAPPalpha and sAPPbeta by ELISA.
      Immunoprecipitation with a C-terminal antibody to remove sAPPf reduced by ~30%
      the determinations of sAPPalpha and sAPPbeta by ELISA, whereas
      immunoprecipitation with an APPbeta antibody reduced by ~80% the determination of
      sAPPf and sAPPalpha. CONCLUSIONS: The presence of sAPPf and sAPP heteromers
      should be taken into consideration when exploring the levels of sAPPalpha and
      sAPPbeta as potential CSF biomarkers.

PMID- 25573164
TI  - Challenges associated with immunological scores for the prediction of the risk of
      infection after transplant.

PMID- 25573163
TI  - Degradable polyphosphoester-based silver-loaded nanoparticles as therapeutics for
      bacterial lung infections.
AB  - In this study, a new type of degradable polyphosphoester-based polymeric
      nanoparticle, capable of carrying silver cations via interactions with alkyne
      groups, has been developed as a potentially effective and safe treatment for lung
      infections. It was found that up to 15% (w/w) silver loading into the
      nanoparticles could be achieved, consuming most of the pendant alkyne groups
      along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded
      nanoparticles released silver in a controlled and sustained manner over 5 days,
      and displayed enhanced in vitro antibacterial activities against cystic fibrosis
      associated pathogens and decreased cytotoxicity to human bronchial epithelial
      cells, in comparison to silver acetate. 

PMID- 25573165
TI  - Upper limb joint angle measurement in occupational health.
AB  - Usual human motion capture systems are designed to work in controlled laboratory
      conditions. For occupational health, instruments that can measure during normal
      daily life are essential, as the evaluation of the workers' movements is a key
      factor to reduce employee injury- and illness-related costs. In this paper, we
      present a method for joint angle measurement, combining inertial sensors
      (accelerometers and gyroscopes) and magnetic sensors. This method estimates wrist
      flexion, wrist lateral deviation, elbow flexion, elbow pronation, shoulder
      flexion, shoulder abduction and shoulder internal rotation. The algorithms avoid
      numerical integration of the signals, which allows for long-time estimations
      without angle estimation drift. The system has been tested both under laboratory
      and field conditions. Controlled laboratory tests show mean estimation errors
      between 0.06 degrees  and of 1.05 degrees , and standard deviation between 2.18
      degrees  and 9.20 degrees . Field tests seem to confirm these results when no
      ferromagnetic materials are close to the measurement system. 

PMID- 25573166
TI  - Caveat emptor: lessons learned from the endovascular treatment of complex aortic
      pathologies.

PMID- 25573167
TI  - Factors associated with maternal death from direct pregnancy complications: a UK
      national case-control study.
AB  - OBJECTIVE: To investigate the factors associated with maternal death from direct
      pregnancy complications in the UK. DESIGN: Unmatched case-control analysis.
      SETTING: All hospitals caring for pregnant women in the UK. POPULATION: A total
      of 135 women who died (cases) between 2009 and 2012 from eclampsia, pulmonary
      embolism, severe sepsis, amniotic fluid embolism, and peripartum haemorrhage,
      using data from the Confidential Enquiry into Maternal Death, and another 1661
      women who survived severe complications (controls) caused by these conditions
      (2005-2013), using data from the UK Obstetric Surveillance System. METHODS:
      Multivariable regression analyses were undertaken to identify the factors that
      were associated with maternal deaths and to estimate the additive odds associated
      with the presence of one or more of these factors. MAIN OUTCOME MEASURES: Odds
      ratios associated with maternal death and population-attributable fractions, with
      95% confidence intervals. Incremental risk of death associated with the factors
      using a 'risk factors' score. RESULTS: Six factors were independently associated
      with maternal death: inadequate use of antenatal care (adjusted odds ratio, aOR
      15.87, 95% CI 6.73-37.41); substance misuse (aOR 10.16, 95% CI 1.81-57.04);
      medical comorbidities (aOR 4.82, 95% CI 3.14-7.40); previous pregnancy problems
      (aOR 2.21, 95% CI 1.34-3.62); hypertensive disorders of pregnancy (aOR 2.44, 95%
      CI 1.31-4.52); and Indian ethnicity (aOR 2.70, 95% CI 1.14-6.43). Of the
      increased risk associated with maternal death, 70% (95% CI 66-73%) could be
      attributed to these factors. Odds associated with maternal death increased by
      three and a half times per unit increase in the 'risk factor' score (aOR 3.59,
      95% CI 2.83-4.56). CONCLUSIONS: This study shows that medical comorbidities are
      importantly associated with direct (obstetric) deaths. Further studies are
      required to understand whether specific aspects of care could be improved to
      reduce maternal deaths among women with medical comorbidities in the UK.

PMID- 25573168
TI  - Viral diversity and clonal evolution from unphased genomic data.
AB  - BACKGROUND: Clonal expansion is a process in which a single organism reproduces
      asexually, giving rise to a diversifying population. It is pervasive in nature,
      from within-host pathogen evolution to emergent infectious disease outbreaks.
      Standard phylogenetic tools rely on full-length genomes of individual pathogens
      or population consensus sequences (phased genotypes). METHODS: We introduce two
      measures of diversity to study the evolution of clonal populations using unphased
      genomic data, which eliminate the need to construct full-length genomes. Our
      method follows a maximum likelihood approach to estimate evolutionary rates and
      times to the most recent common ancestor, based on a relaxed molecular clock
      model; independent of a growth model. Deviations from neutral evolution indicate
      the presence of selection and bottleneck events. RESULTS: We evaluated our
      methods in silico and then compared it against existing approaches with the well
      characterized 2009 H1N1 influenza pandemic. We then applied our method to high
      throughput genomic data from marburgvirus-infected non-human primates and
      inferred the time of infection and the intra-host evolutionary rate, and
      identified purifying selection in viral populations. CONCLUSIONS: Our method has
      the power to make use of minor variants present in less than 1% of the population
      and capture genomic diversification within days of infection, making it an ideal
      tool for the study of acute RNA viral infection dynamics.

PMID- 25573170
TI  - Legal recognition of same-sex couples and family formation.
AB  - It has long been debated how legalizing same-sex marriage would affect (different
      sex) family formation. In this article, I use data on OECD member countries for
      the period 1980-2009 to examine the effects of the legal recognition of same-sex
      couples (through marriage or an alternative institution) on different-sex
      marriage, divorce, and extramarital births. Estimates from difference-in
      difference models indicate that the introduction of same-sex marriage or of
      alternative institutions has no negative effects on family formation. These
      findings are robust to a multitude of specification checks, including the
      construction of counterfactuals using the synthetic control method. In addition,
      the country-by-country case studies provide evidence of homogeneity of the
      estimated effects. 

PMID- 25573171
TI  - Identification of suitable reference genes for gene expression studies using
      quantitative polymerase chain reaction in lung cancer in vitro.
AB  - The present study aimed to examine 10 housekeeping genes (HKGs), including 18s
      ribosomal RNA (18S), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribosomal
      protein large P0 (RPLP0), beta-actin (ACTB), peptidylprolyl isomerase A (PPIA),
      phosphoglycerate kinase-1 (PGK1), beta-2-microglobulin (B2M), ribosomal protein
      LI3a (RPL13A), hypoxanthine phosphoribosyl transferase-1 (HPRT1) and TATA box
      binding protein (TBP) in order to identify the most stable and suitable reference
      genes for use in expression studies in non-small cell lung cancer. The mRNA
      expression encoding the panel of the 10 HKGs was determined using reverse
      transcription-quantitative PCR (RT-qPCR) in human lung cancer cell lines. Three
      software programs, BestKeeper, NormFinder and geNorm, were used to ascertain the
      most suitable reference genes to normalize the RNA input. The present study
      examined three lung cancer cell lines (A549, NCI-H446 and NCI-H460). The analysis
      of the experimental data using BestKeeper software revealed that all 10 HKGs were
      stable, with GADPH, followed by 18S being the most stable genes and PPIA and
      HPRT1 being the least stable genes. The NormFinder software results demonstrated
      that PPIA followed by ACTB were the most stable and B2M and RPLP0 were the least
      stable. The geNorm software results revealed that ACTB and PGK1, followed by PPIA
      were the most stable genes and B2M and RPLP0 were identified as the least stable
      genes. Due to discrepancies in the ranking orders of the reference genes obtained
      by different analyzing software programs, it was not possible to determine a
      single universal reference gene. The suitability of selected reference genes
      requires unconditional validation prior to each study. Based on the three
      analyzing programs, ACTB, PPIA and PGK1 were the most stable reference genes in
      lung cancer cell lines.

PMID- 25573169
TI  - Pregnancy intentions, maternal behaviors, and infant health: investigating
      relationships with new measures and propensity score analysis.
AB  - The premise that unintended childbearing has significant negative effects on the
      behavior of mothers and on the health of infants strongly influences public
      health policy and much of current research on reproductive behaviors. Yet, the
      evidence base presents mixed findings. Using data from the U.S. National Survey
      of Family Growth, we employ a measure of pregnancy intentions that incorporates
      the extent of mistiming, as well as the desire scale developed by Santelli et al.
      (Studies in Family Planning, 40, 87-100, 2009). Second, we examine variation in
      the characteristics of mothers within intention status groups. Third, we account
      for the association of mothers' background characteristics with their pregnancy
      intentions and with the outcomes by employing propensity score weighting. We find
      that weighting eliminated statistical significance of many observed associations
      of intention status with maternal behaviors and birth outcomes, but not all.
      Mistimed and unwanted births were still less likely to be recognized early in
      pregnancy than intended ones. Fewer unwanted births received early prenatal care
      or were breast-fed, and unwanted births were also more likely than intended
      births to be of low birth weight. Relative to births at the highest level of the
      desire scale, all other births were significantly less likely to be recognized
      early in pregnancy and to receive early prenatal care. 

PMID- 25573172
TI  - Dickkopf-3 (Dkk3) induces apoptosis in cisplatin-resistant lung adenocarcinoma
      cells via the Wnt/beta-catenin pathway.
AB  - Previous studies have shown that Dickkopf-3 (Dkk3) is inactivated in lung cancer
      cells, while the inactivation of the Wnt/beta-catenin signaling pathway by Dkk3
      inhibits lung cancer progression. In the present study, we investigated whether
      Dkk3 enhances the sensitivity of lung cancer cells to cisplatin. A549, Calu1 and
      H460 lung adenocarcinoma cell lines were transfected with DKK3 siRNA, while the
      cisplatin-resistant subline A549cis was transfected with DKK3. DKK3 expression
      was attenuated in A549cis, Calu1cis and H460cis compared to A549, Calu1 and H460,
      respectively. Lung adenocarcinoma cell growth, proliferation, apoptosis, cell
      cycle in vitro and in vivo were then analyzed. DKK3 knockdown by siRNA
      transfection rendered A549, Calu1 and H460 resistant to cisplatin. As a result of
      DKK3 transfection, the expression of DKK3 and E-cadherin was significantly
      upregulated, while that of MMP7, survivin, c-myc and cyclin D1 was downregulated.
      DKK3 overexpression retarded cell proliferation, induced cell cycle arrest and
      apoptosis, and reduced cell invasive ability in the A549 and A549cis cells. In
      addition, the proportions of apoptotic cells and the PARP level were
      significantly increased in A549cis- and H460cis-DKK3 cells treated with
      cisplatin. Moreover, tumor growth was retarded more in cisplatin-treated nude
      mice seeded with A549cis-DKK3 cells than with A549cis cells. Cell viability
      increased with the pretreatment of SB216763 for 2 h in A549cis and A549cis-DKK3
      cells incubated with cisplatin (1 uM) for 72 h. In conclusion, the re-activation
      of Dkk3 enhances the chemosensitivity to cisplatin in cisplatin-resistant lung
      adenocarcinoma cell lines, which requires additional studies to realize this
      potential in clinical use.

PMID- 25573173
TI  - Human and mouse tissue-engineered small intestine both demonstrate digestive and
      absorptive function.
AB  - Short bowel syndrome (SBS) is a devastating condition in which insufficient small
      intestinal surface area results in malnutrition and dependence on intravenous
      parenteral nutrition. There is an increasing incidence of SBS, particularly in
      premature babies and newborns with congenital intestinal anomalies. Tissue
      engineered small intestine (TESI) offers a therapeutic alternative to the current
      standard treatment, intestinal transplantation, and has the potential to solve
      its biggest challenges, namely donor shortage and life-long immunosuppression. We
      have previously demonstrated that TESI can be generated from mouse and human
      small intestine and histologically replicates key components of native intestine.
      We hypothesized that TESI also recapitulates native small intestine function.
      Organoid units were generated from mouse or human donor intestine and implanted
      into genetically identical or immunodeficient host mice. After 4 wk, TESI was
      harvested and either fixed and paraffin embedded or immediately subjected to
      assays to illustrate function. We demonstrated that both mouse and human tissue
      engineered small intestine grew into an appropriately polarized sphere of intact
      epithelium facing a lumen, contiguous with supporting mesenchyme, muscle, and
      stem/progenitor cells. The epithelium demonstrated major ultrastructural
      components, including tight junctions and microvilli, transporters, and
      functional brush-border and digestive enzymes. This study demonstrates that
      tissue-engineered small intestine possesses a well-differentiated epithelium with
      intact ion transporters/channels, functional brush-border enzymes, and similar
      ultrastructural components to native tissue, including progenitor cells, whether
      derived from mouse or human cells. 

PMID- 25573174
TI  - Distinct afferent innervation patterns within the human proximal and distal
      esophageal mucosa.
AB  - Little is known about the mucosal phenotype of the proximal human esophagus.
      There is evidence to suggest that the proximal esophagus is more sensitive to
      chemical and mechanical stimulation compared with the distal. This may have
      physiological relevance (e.g., in prevention of aspiration of gastroesophageal
      refluxate), but also pathological relevance (e.g., in reflux perception or
      dysphagia). Reasons for this increased sensitivity are unclear but may include
      impairment in mucosal barrier integrity or changes in sensory innervation. We
      assessed mucosal barrier integrity and afferent nerve distribution in the
      proximal and distal esophagus of healthy human volunteers. In 10 healthy
      volunteers baseline proximal and distal esophageal impedance was measured in
      vivo. Esophageal mucosal biopsies from the distal and proximal esophagus were
      taken, and baseline transepithelial electrical resistance (TER) was measured in
      Ussing chambers. Biopsies were examined immunohistochemically for presence and
      location of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers.
      In a further four healthy volunteers we investigated for colocalization of CGRP
      and protein gene product (PGP) 9.5 immunoreactivity in nerve fibers. Baseline
      impedance was higher in the proximal than in the distal esophagus [2,936 Omega
      (SD578) vs. 2,229 Omega (SD821); P = 0.03], however, baseline TER was not
      significantly different between them. Mucosal CGRP-immunoreactive nerves were
      found in the epithelium of both proximal and distal esophagus, but were located
      more superficially in the proximal mucosa compared with the distal [11.5 (SD7)
      vs. 21.7 (SD5) cell layers from lumen, P = 0.002] 19% of proximal, and 10% of
      distal mucosal PGP-immunoreactive fibers colocalized with CGRP. PGP
      immunoreactive fibers were also significantly closer to the luminal surface in
      the proximal compared with the distal esophagus (P < 0.001). We conclude that
      mucosal barrier integrity is similar in proximal and distal esophagus, but
      proximal mucosal afferent nerves are in a more superficial location. The enhanced
      sensitivity to reflux-evoked symptoms of the proximal esophagus most likely has
      an anatomical basis. 

PMID- 25573175
TI  - Chronic NOS inhibition accelerates NAFLD progression in an obese rat model.
AB  - The progression in nonalcoholic fatty liver disease (NAFLD) to nonalcoholic
      steatohepatitis is a serious health concern, but the underlying mechanisms remain
      unclear. We hypothesized that chronic inhibition of nitric oxide (NO) synthase
      (NOS) via N(omega)-nitro-L-arginine methyl ester (L-NAME) would intensify liver
      injury in a rat model of obesity, insulin resistance, and NAFLD. Obese Otsuka
      Long-Evans Tokushima fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO)
      rats received control or L-NAME (65-70 mg.kg(-1).day(-1))-containing drinking
      water for 4 wk. L-NAME treatment significantly (P < 0.05) reduced serum NO
      metabolites and food intake in both groups. Remarkably, despite no increase in
      body weight, L-NAME treatment increased hepatic triacylglycerol content (+40%, P
      < 0.05) vs. control OLETF rats. This increase was associated with impaired (P <
      0.05) hepatic mitochondrial state 3 respiration. Interestingly, the opposite
      effect was found in LETO rats, where L-NAME increased (P < 0.05) hepatic
      mitochondrial state 3 respiration. In addition, L-NAME induced a shift toward
      proinflammatory M1 macrophage polarity, as indicated by elevated hepatic CD11c (P
      < 0.05) and IL-1beta (P = 0.07) mRNA in OLETF rats and reduced expression of the
      anti-inflammatory M2 markers CD163 and CD206 (P < 0.05) in LETO rats. Markers of
      total macrophage content (CD68 and F4/80) mRNA were unaffected by L-NAME in
      either group. In conclusion, systemic NOS inhibition in the obese OLETF rats
      reduced hepatic mitochondrial respiration, increased hepatic triacylglycerol
      accumulation, and increased hepatic inflammation. These findings suggest an
      important role for proper NO metabolism in the hepatic adaptation to obesity.

PMID- 25573178
TI  - Gas-phase reaction of CeVO5(+) cluster ions with C2H4: the reactivity of cluster
      bonded peroxides.
AB  - Cerium-vanadium oxide cluster cations CeVO5(+) were generated by laser ablation,
      mass-selected using a quadrupole mass filter, thermalized through collisions with
      helium atoms, and then reacted with ethene molecules in a linear ion trap
      reactor. The cluster reactions have been characterized by time-of-flight mass
      spectrometry and density functional theory calculations. The CeVO5(+) cluster has
      a closed-shell electronic structure and contains a peroxide (O2(2-)) unit. The
      cluster bonded O2(2-) species is reactive enough to oxidize a C2H4 molecule to
      generate C2H4O2 that can be an acetic acid molecule. Atomic oxygen radicals (O(
      )), superoxide radicals (O2(-)), and peroxides are the three common reactive
      oxygen species. The reactivity of cluster bonded O(-) and O2(-) radicals has been
      widely studied while the O2(2-) species were generally thought to be much less
      reactive or inert toward small molecules under thermal collision conditions. This
      work is among the first to report the reactivity of the peroxide unit on
      transition metal oxide clusters with hydrocarbon molecules, to the best of our
      knowledge. 

PMID- 25573176
TI  - Transcriptional corepressor MTG16 regulates small intestinal crypt proliferation
      and crypt regeneration after radiation-induced injury.
AB  - Myeloid translocation genes (MTGs) are transcriptional corepressors implicated in
      development, malignancy, differentiation, and stem cell function. While MTG16
      loss renders mice sensitive to chemical colitis, the role of MTG16 in the small
      intestine is unknown. Histological examination revealed that Mtg16(-/-) mice have
      increased enterocyte proliferation and goblet cell deficiency. After exposure to
      radiation, Mtg16(-/-) mice exhibited increased crypt viability and decreased
      apoptosis compared with wild-type (WT) mice. Flow cytometric and
      immunofluorescence analysis of intestinal epithelial cells for phospho-histone
      H2A.X also indicated decreased DNA damage and apoptosis in Mtg16(-/-) intestines.
      To determine if Mtg16 deletion affected epithelial cells in a cell-autonomous
      fashion, intestinal crypts were isolated from Mtg16(-/-) mice. Mtg16(-/-) and WT
      intestinal crypts showed similar enterosphere forming efficiencies when cultured
      in the presence of EGF, Noggin, and R-spondin. However, when Mtg16(-/-) crypts
      were cultured in the presence of Wnt3a, they demonstrated higher enterosphere
      forming efficiencies and delayed progression to mature enteroids. Mtg16(-/-)
      intestinal crypts isolated from irradiated mice exhibited increased survival
      compared with WT intestinal crypts. Interestingly, Mtg16 expression was reduced
      in a stem cell-enriched population at the time of crypt regeneration. This is
      consistent with MTG16 negatively regulating regeneration in vivo. Taken together,
      our data demonstrate that MTG16 loss promotes radioresistance and impacts
      intestinal stem cell function, possibly due to shifting cellular response away
      from DNA damage-induced apoptosis and towards DNA repair after injury. 

PMID- 25573177
TI  - Giardia duodenalis-induced alterations of commensal bacteria kill Caenorhabditis
      elegans: a new model to study microbial-microbial interactions in the gut.
AB  - Giardia duodenalis is the most common cause of parasitic diarrhea worldwide and a
      well-established risk factor for postinfectious irritable bowel syndrome. We
      hypothesized that Giardia-induced disruptions in host-microbiota interactions may
      play a role in the pathogenesis of giardiasis and in postgiardiasis disease.
      Functional changes induced by Giardia in commensal bacteria and the resulting
      effects on Caenorhabditis elegans were determined. Although Giardia or bacteria
      alone did not affect worm viability, combining commensal Escherichia coli
      bacteria with Giardia became lethal to C. elegans. Giardia also induced killing
      of C. elegans with attenuated Citrobacter rodentium espF and map mutant strains,
      human microbiota from a healthy donor, and microbiota from inflamed colonic sites
      of ulcerative colitis patient. In contrast, combinations of Giardia with
      microbiota from noninflamed sites of the same patient allowed for worm survival.
      The synergistic lethal effects of Giardia and E. coli required the presence of
      live bacteria and were associated with the facilitation of bacterial colonization
      in the C. elegans intestine. Exposure to C. elegans and/or Giardia altered the
      expression of 172 genes in E. coli. The genes affected by Giardia included
      hydrogen sulfide biosynthesis (HSB) genes, and deletion of a positive regulator
      of HSB genes, cysB, was sufficient to kill C. elegans even in the absence of
      Giardia. Our findings indicate that Giardia induces functional changes in
      commensal bacteria, possibly making them opportunistic pathogens, and alters host
      microbe homeostatic interactions. This report describes the use of a novel in
      vivo model to assess the toxicity of human microbiota. 

PMID- 25573179
TI  - Dislocation rates following primary total hip arthroplasty have plateaued in the
      Medicare population.
AB  - The purpose of this study was to determine if the use of larger femoral head
      diameters, in combination with recent practice including enhanced soft tissue
      choices and various operative exposure choices has led to any further decline in
      dislocation rates. 51,901 patients undergoing primary THA were identified from 5%
      Medicare Part B (physician/carrier) claims between January 1, 1997 and December
      31, 2011. Dislocation rate at 6 months following THA was 2.84% over the study
      period (1997-2011). From 2005 to 2011, dislocation rates following primary THA
      have plateaued in the United States at approximately 2%. This suggests that the
      full benefits using large femoral head sizes are now realized. For further
      improvement in dislocation rates, a greater emphasis will be required on patient
      selection, surgical technique and component alignment.

PMID- 25573180
TI  - Revision of Recalled Modular Neck Rejuvenate and ABG Femoral Implants.
AB  - Modular neck femoral stems have been associated with adverse local tissue
      reactions (ALTR), leading to a voluntary recall, but these effects have not been
      well-characterized. A retrospective review of intraoperative findings and
      cobalt/chromium levels was performed in 103 hips undergoing revision for ALTR.
      The average preoperative serum cobalt level was 7.6 MUg/L (range 1.1-23 MUg/L)
      and chromium level was 1.8 MUg/L (range 0.1-6.8 MUg/L). Metallic sludge was noted
      in 100%, synovitis in 98%, pericapsular rind in 82%, and calcar erosion in 85%.
      An osteotomy was required for removal in 44%. We concluded that revision of
      modular neck femoral stems is associated with increased preoperative metal ion
      levels and stem-neck corrosion. Despite advanced stem explantation techniques,
      osteotomy was frequently required, leading to increased morbidity.

PMID- 25573182
TI  - Predicting inpatient stay lasting 2 midnights or longer after robotic surgery for
      endometrial cancer.
AB  - OBJECTIVE: To estimate the rate of inpatient stay and the factors predicting
      inpatient status after robotic surgery for endometrial cancer following the
      change in the Medicare definition of "inpatient" to include hospitalization
      spanning 2 midnights. DESIGN: Retrospective chart review (Canadian Task Force
      classification II-1). SETTING: Academic hospital. PATIENTS: All patients (n =
      395) with endometrial cancer who underwent robotic surgical management between
      2006 and 2010. INTERVENTION: The outpatient stay group with hospitalization
      spanning 1 midnight was compared with the inpatient stay group with
      hospitalization spanning 2 midnights or longer through estimation of the adjusted
      relative risk (aRR) for various characteristics of interest. RESULTS: Ninety-six
      of 395 patients (24.3%) stayed at least 2 midnights and thus were deemed
      inpatients. Clinical factors associated with inpatient stay were increasing age,
      history of myocardial infarction (aRR, 2.0; 95% confidence interval [CI], 1.0
      3.7), surgery start time at or after 12 noon (aRR, 1.7; 95% CI, 1.2-2.4),
      perioperative blood transfusion (aRR, 3.2; 95% CI, 2.3-4.5), and surgery
      performed in the year 2010 (aRR, 0.5; 95% CI, 0.3-0.7). Age >= 60 years was
      associated with at least a 2-fold adjusted risk of prolonged hospitalization.
      Body mass index, other medical comorbidities, operative duration, estimated blood
      loss, and performance of lymphadenectomy or additional surgical procedures were
      not identified as significant risk factors. CONCLUSION: Approximately 75% of the
      patients undergoing robotic surgery for endometrial cancer were discharged as
      outpatients. Recognition of factors predicting inpatient stay can improve
      hospital resource allocation and throughput in women undergoing robotic surgery
      for endometrial cancer.

PMID- 25573183
TI  - Effect of hemostatic method on ovarian reserve following laparoscopic
      endometrioma excision; comparison of suture, hemostatic sealant, and bipolar
      dessication. A systematic review and meta-analysis.
AB  - We reviewed the literature to determine whether different hemostatic methods used
      following laparoscopic endometrioma excision have differing effects on ovarian
      reserve. We performed a systematic literature search using the Cochrane Central
      Register of Controlled Trials, MEDLINE, Embase, and Ovid MEDLINE In-Process &
      Other Non-Indexed Citations databases to identify studies comparing the rate of
      change in levels of serum anti-Mullerian hormone (AMH) at 3 months after
      laparoscopic endometrioma excision using bipolar dessication (BD) or
      suturing/application of a hemostatic sealant (HS) for hemostasis. Abstracts of
      the annual meetings of the American Society of Reproductive Medicine, the
      European Society of Human Reproduction and Embryology, and the American
      Association of Gynecological Laparoscopists were searched as well. A total of 712
      articles were identified, of which 6 were included in the qualitative analysis.
      Four studies involving 213 women were included in the meta-analysis. Our
      qualitative analysis suggested that BD is more detrimental to ovarian reserve
      than alternative hemostatic methods. There is moderate-quality evidence favoring
      HS and low-quality evidence favoring sutures over BD. The meta-analysis also
      showed that alternative hemostatic methods are associated with significantly less
      decline in ovarian reserve compared with BD. The mean decline in serum AMH levels
      was 6.95% less with alternative hemostatic methods than with BD (95% CI, -13.0%
      to -0.9%; p = .02) at 3 months after surgery. According to the best available
      evidence, the use of BD should be cautiously limited, even avoided when possible,
      during endometrioma excision in women who desire to have children. 

PMID- 25573181
TI  - Cardiac and inflammatory biomarkers do not correlate with volume of heart or lung
      receiving radiation.
AB  - BACKGROUND: Thoracic and cardiac irradiation increases the risk of pulmonary and
      cardiovascular disease. In addition, radiation, often in combination with
      chemotherapy, can cause treatment-related pneumonitis. Previously, we showed that
      the common marker for cardiac damage, troponin T, was not elevated by
      chemoradiation [Lung Cancer 62:351-355, 2008]. In this study, we explore whether
      dose-volume metrics and biomarkers for cardiac damage, inflammation or
      angiogenesis could identify patients receiving thoracic radiation who would later
      have cardiac or pulmonary complications. FINDINGS: To this end, we quantified
      cardiac biomarkers including c-reactive protein (cRP) as well as a panel of
      angiogenic and inflammatory molecules in thirty patients who received radiation
      therapy to the thorax with or without concurrent chemotherapy between May 2006
      and May 2007. Serum was collected at baseline, 2 weeks into radiation treatment
      and at the completion of radiation therapy. Heart and lung dosimetric parameters
      and clinical risk factors were also examined, along with the monitoring of
      adverse pulmonary and cardiac events during follow-up. Contrary to our
      hypothesis, there was no correlation between serum biomarker levels and cardiac
      radiation dose. Similarly there was little association between lung dose-volume
      metrics and inflammatory or angiogenic biomarkers. Furthermore, there was no
      correlation with serum biomarkers and adverse pulmonary or cardiovascular events.
      CONCLUSION: Based on these data, acute elevations in serum biomarkers of cardiac
      damage, inflammation or angiogenesis should not be attributed to thoracic
      (chemo)radiation and elevations in such biomarkers of tissue damage should be
      further evaluated.

PMID- 25573184
TI  - Subendometrial blood flow changes by 3-dimensional power Doppler ultrasound after
      hysteroscopic lysis of severe intrauterine adhesions: preliminary study.
AB  - OBJECTIVE: To evaluate the changes in subendometrial blood flow and endometrial
      volume after hysteroscopic lysis of severe intrauterine adhesions (IUAs). DESIGN:
      A pilot observational study. Forty infertile women with severe IUAs served as
      their own controls and were included in this study only once, to avoid selection
      bias. INTERVENTION: Three-dimensional power Doppler ultrasound was performed in
      all patients 1 day before hysteroscopic lysis of severe IUA, and repeated 1 month
      later, to assess subendometrial blood flow [as measured by vascularization index
      (VI), flow index (FI), and vascularization flow index (VFI)] and endometrial
      volume. Main outcome measures were subendometrial blood flow (VI, FI, VFI) and
      endometrial volume. RESULTS: There were statistically significant postoperative
      increases in endometrial volume, VI, FI, and VFI. Subendometrial blood flow
      improved in 14 women (35%), and menstrual improvement occurred in 15 women
      (37.5%). CONCLUSION: Hysteroscopic lysis of severe IUAs improves subendometrial
      blood flow, with subsequent increases in endometrial volume.

PMID- 25573185
TI  - The AiMu MCu Intrauterine Device.

PMID- 25573186
TI  - Sonographic findings in postmenopausal women with a prior endometrial ablation:
      interpretation and management of women with endometrial thickening and bleeding.
AB  - OBJECTIVE: To understand the meaning of endometrial thickening and bleeding in
      postmenopausal women who had previously undergone endometrial ablation (EA).
      DESIGN: Retrospective observational study. Canadian Task Force III. SETTING:
      Obstetrics and Gynecology Unit, Magna Graecia University, Catanzaro, Italy.
      PATIENTS: Sixty-three postmenopausal women who had previously undergone EA.
      INTERVENTIONS: A retrospective evaluation of clinical charts of postmenopausal
      women who had a follow-up visit after EA between January 2000 and August 2014.
      MEASUREMENTS AND MAIN RESULTS: The rates of endometrial thickening (with or
      without bleeding), endometrial atrophy, and cancer were determined.
      Postmenopausal bleeding was reported in 9 patients (14.3%). Endometrial
      thickening was observed in 51 patients (80.9%; mean +/- SD endometrial thickness,
      7.7 +/- 3.0 mm). A significantly (p < .05) greater number of patients with an
      endometrial thickness of 5 to 10 mm was observed compared with those with an
      endometrial thickness of <5 mm or >10 mm. A significant (p = .001) difference in
      increase in endometrial thickness was observed between patients with and without
      bleeding. Overall, hysteroscopy plus endometrial biopsy was scheduled in 24
      patients. In all bleeding women, a histological diagnosis of endometrial atrophy
      was demonstrated. Concerning bleeding-free women, in 14 patients with endometrial
      thickening of >10 mm, mucosal atrophy was detected. The only bleeding-free
      patient in whom an endometrial echogenic fluid collection was detected had a
      histological diagnosis of endometrioid endometrial cancer. Thus, patients who
      underwent hysteroscopy had a 95.8% rate of mucosal atrophy and a 4.2% rate of
      endometrial cancer. The overall cancer rate in our global population (menopause
      with previous EA) was 1.6%. CONCLUSION: Postmenopausal bleeding and sonographic
      detection of endometrial thickening in patients with previous EA are not
      necessarily related to a malignant disease. Nonetheless, ultrasound visualization
      of endometrial thickening plus an echogenic endometrial fluid collection in these
      patients always warrants an invasive diagnostic procedure regardless of whether
      or not bleeding is reported.

PMID- 25573187
TI  - Hypotonic stress-induced calcium signaling in Saccharomyces cerevisiae involves
      TRP-like transporters on the endoplasmic reticulum membrane.
AB  - Saccharomyces cerevisiae cells respond to hypotonic stress (HTS) by a cytosolic
      calcium rise, either generated by an influx of calcium from extracellular medium,
      when calcium is available, or by a release from intracellular stores in scarcity
      of extracellular calcium. Calcium release from intracellular compartments is
      peculiarly inhibited by external calcium in a calcineurin-independent and Cch1-,
      but not Mid1-, driven manner. HTS-induced calcium release is also negatively
      regulated by the ER protein Cls2 and involves a poorly characterized protein,
      FLC2/YAL053W gene product, previously proposed to be required for FAD transport
      in the ER, albeit, due to its molecular features, it was also previously
      classified as an ion transporter. A computational analysis revealed that this
      gene and its three homologs in S. cerevisiae, together with previously identified
      Schizosaccharomyces pombe pkd2 and Neurospora crassa calcium-related spray
      protein, belong to a fungal branch of TRP-like ion transporters related to human
      mucolipin and polycystin 2 calcium transporters. Moreover, disruption of FLC2
      gene confers severe sensitivity to Calcofluor white and hyper-activation of the
      cell wall integrity MAPK cascade, suggesting a role in cell wall maintenance as
      previously suggested for the fission yeast homolog. Perturbation in cytosolic
      resting calcium concentration and hyper-activation of calcineurin in
      exponentially growing cells suggest a role for this transporter in calcium
      homeostasis in yeast. 

PMID- 25573188
TI  - Assessment of two extraction methods to determine pesticides in soils, sediments
      and sludges. Application to the Turia River Basin.
AB  - Pressurized liquid extraction (PLE) and Quick, Easy, Cheap, Effective, Rugged and
      Safe (QuEChERS) extraction methods were optimized for the simultaneous
      determination of 50 pesticides in sediment, soils and sewage sludge. For QuEChERS
      development, several buffers and dispersive solid-phase extraction clean-up
      (dSPE) sorbents were tested. In the PLE method, several parameters affecting the
      extraction efficiency, such as organic solvent, amount of sample, cell size,
      temperature, pressure, static time, number of cycles and % of flush, as well as
      sorbent used for the on-line clean up, were also evaluated. PLE and QuEChERS were
      assessed and compared in obtained recoveries (33-89% versus 25-120%), number of
      pesticides for which recoveries are in the range of 80-100% (up to 13 versus up
      to 35) and cost of the approach. QuEChERS procedure was faster, cheaper and
      easier to perform. Recoveries were around 80% (at 50ngg(-1) d.w.) and the matrix
      effect was less than -20% using matrix-matched standard calibration curve for
      most of the analytes. The limits of quantification were between 0.1 and 10ngg(-1)
      (d.w.) except for alachlor and acetochlor. Repeatability and reproducibility were
      lower than 28% (%RSD, n=5). Soil, sediment and sludge samples, taken from the
      Turia River Basin, were analyzed by QuEChERS to determine pesticides.
      Chlorpyrifos (up to 65.3ngg(-1) d.w.) was the most frequent and at higher
      concentrations. Thiabendazole, imazalil, diazinon, pyriproxyfen, hexythiazox,
      carbofuran, isoproturon, terbuthylazine and terbumeton were also found in some
      samples. 

PMID- 25573189
TI  - Two-stage fractionation of polar alkaloids from Rhizoma coptidis by
      countercurrent chromatography considering the strategy of reactive extraction.
AB  - Separation of polar alkaloids by countercurrent chromatography (CCC) is
      challengeable due to their close partition behaviors in solvent system. In this
      paper, a two-stage method for isolation of epiberberine, jatrorrhizine,
      palmatine, coptisine, and berberine from Rhizoma coptidis was presented. The
      first stage separation performed on CCC was based on the principle of reactive
      extraction. Trifluoroacetic acid was acted as a modulator to selectively react
      with alkaloids, which changed their partition coefficients in solvent system.
      Purified epiberberine and other partially separated targets were eluted by
      ammonium adjusted mobile phase. In the second stage, four alkaloids were purified
      in pH-zone-refining CCC mode. All the targets collected were over 97% pure
      determined by HPLC. The method developed demonstrates performing of reactive
      extraction on standard CCC as an option for separation of polar alkaloids from
      medicinal plants. 

PMID- 25573190
TI  - Occupancy of the Departments of Intensive Care Medicine in Catalonia (Spain): A
      prospective, analytical cohort study.
AB  - BACKGROUND: Before deciding increases in the number or capacitance of Intensive
      Care Units (ICUs), or the regionalization of Units, it is essential to know their
      present effectiveness. OBJECTIVE: To analyze the daily occupancy rate of ICUs in
      Catalonia (Spain) and the frequency of denied admission due to lack of capacity.
      DESIGN: A prospective, observational multicenter study was carried out.
      PARTICIPANTS: A total of 35 out of 40 ICUs of Catalonia (87%). INTERVENTIONS:
      Daily registry. VARIABLES OF INTEREST: Open beds and free beds, patients not
      discharged due to unavailability of ward beds, critically ill patients not
      admitted due to a lack of ICU beds, and rate of transfer to other ICUs.
      STATISTICAL ANALYSIS: A descriptive cohort analysis was made. RESULTS: Daily
      averages were 383 open ICU beds, 58 available beds (15%), and 16 patients not
      discharged due to unavailability of ward beds. Each day 6 patients on average
      were not admitted due to a lack of ICU beds, and one of them (16%) was
      transferred to another ICU. The mean occupancy rate was 83+/-19%, and a 100%
      occupancy rate was reported in 35% of the registries. A subanalysis of the 24
      public hospitals demonstrated slightly higher occupancy (87+/-16%), with a 100%
      occupancy rate reported in 38% of the registries. CONCLUSIONS: The mean occupancy
      rate of Catalonian ICUs may appear correct, but in some Units over-occupancy very
      often precludes early ICU treatment and even ICU admission for a significant
      number of critically ill patients.

PMID- 25573191
TI  - MicroRNA-125b may function as an oncogene in lung cancer cells.
AB  - The present study aimed to investigate the biofunctions of microRNA (miR)-125b on
      lung cancer cells. A miR genechip array was used to examine the differential
      expression of miRs between 95D lung cancer cells and 16 human bronchial
      epithelial (HBE) cells. Overexpression of miR-125b was observed in the cell lines
      and in the lung carcinoma tissues compared with the adjacent tissues, confirmed
      using reverse transcription quantitative polymerase chain reaction. Bioinformatic
      analysis of miR-125b was also performed, including target prediction, gene
      ontology and pathway analysis. MTT, flow cytometry and Transwell assays were also
      used to examine the effect of downregulated miR-125b on the proliferation,
      apoptosis, invasive ability and cell cycle of 95D cells. Significant differences
      were observed in the expression of 45 miRs in the 95D cells compared with those
      in 16HBE cells and the expression of miR-125b was significantly higher in 95D
      cells compared with that in 16HBE cells as well as in lung tumor tissues compared
      with that in adjacent tissues. In addition, inhibition of the expression of miR
      125b in 95D cells induced apoptosis, G1/S phase arrest and reduction of their
      invasive ability. In addition, bioinformatics software predicted that miR-125b
      was involved in the regulation of several pathways associated with cancer,
      including the transforming growth factor-beta, Wnt and mitogen-activated protein
      kinase signaling pathways. These data indicated for the first time, to the best
      of our knowledge, that miR-125b may function as an oncogene in lung cancer.

PMID- 25573192
TI  - Lentivirus-mediated silencing of spindle and kinetochore-associated protein 1
      inhibits the proliferation and invasion of neuronal glioblastoma cells.
AB  - Spindle and kinetochore-associated protein 1 (SKA1) is an important component of
      the human kinetochore, which plays a key role in mitosis. The resent study was
      designed to investigate the role of SKA1 in human glioblastoma. The results of
      the present study demonstrated that SKA1 was expressed in human glioblastoma
      cells. In addition, the knockdown of SKA1 expression in the A172 and U251 human
      glioblastoma cell lines was accomplished using a lentivirus infection method. An
      MTT assay demonstrated that downregulation of SKA1 may inhibit cell
      proliferation, without affecting the cell cycle. Furthermore, knockdown of SKA1
      expression resulted in reduced cell invasion. The results of the present study
      indicated that SKA1 may be a potential target protein for antiproliferative and
      anti-invasive therapeutic strategies of human glioblastoma.

PMID- 25573193
TI  - Environmental enrichment reverses reduction in glucocorticoid receptor expression
      in the hippocampus of and improves behavioral responses of anxiety in early
      malnourished rats.
AB  - We compared glucocorticoid receptor (GR) gene expression in the hippocampus of
      rats subjected to a low protein, "malnourished" diet (M; 6% protein) or a
      control, "well-nourished" diet (W; 16% protein), exposed to different
      environmental stimulation (environmental enrichment, E; no enrichment, N) between
      postnatal day 8 (P8) and P35. Rats were tested on the elevated plus maze (EPM) on
      P36. Male Wistar rats were split into two groups at birth according to diet (M or
      W) and subdivided according to environmental stimulation (E or N). GR expression
      was determined using real-time polymerase chain reaction and GR
      immunohistochemistry in the hippocampus. Our results showed that MN rats spent
      more time and made more entries into the open arms of the EPM compared to W rats.
      On the other hand, ME rats spent a similar percentage of time, and made a similar
      number of entries, in the open arms as WN rats. Following the EPM test, GR mRNA
      expression in the hippocampus was different in MN rats compared to W rats;
      expression was also different between M and ME rats; mRNA and expression of GR
      receptors in WN rats was similar to that observed in WE rats. These data also
      show that the effects of malnutrition on risk assessment in the EPM were reversed
      by E. Early malnutrition may alter GR expression in the hippocampus and
      environmental enrichment may exert a neuroprotective effect on malnutrition
      induced brain injury. 

PMID- 25573194
TI  - One dataset, many conclusions: BOLD variability's complicated relationships with
      age and motion artifacts.
AB  - In recent years, the variability of the blood-oxygen level dependent (BOLD)
      signal has received attention as an informative measure in its own right. At the
      same time, there has been growing concern regarding the impact of motion in fMRI,
      particularly in the domain of resting state studies. Here, we demonstrate that,
      not only does motion (among other confounds) exert an influence on the results of
      a BOLD variability analysis of task-related fMRI data-but, that the exact method
      used to deal with this influence has at least as large an effect as the motion
      itself. This sensitivity to relatively minor methodological changes is
      particularly concerning as studies begin to take on a more applied bent, and the
      risk of mischaracterizing the relationship between BOLD variability and various
      individual difference variables (for instance, disease progression) acquires real
      world relevance. 

PMID- 25573195
TI  - NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced
      potential to induce hyperkalaemia.
AB  - BACKGROUND AND PURPOSE: Inhaled amiloride, a blocker of the epithelial sodium
      channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF)
      patients. However, the dose of amiloride is limited by the mechanism-based side
      effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers
      with a reduced potential to induce hyperkalaemia provide a therapeutic strategy
      to improve mucosal hydration and MCC in the lungs of CF patients. The present
      study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170,
      designed for inhaled delivery, with a reduced potential to induce hyperkalaemia.
      EXPERIMENTAL APPROACH: The in vitro potency and duration of action of NVP-QBE170
      were compared with amiloride and a newer ENaC blocker, P552-02, in primary human
      bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and
      safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia),
      rat (hyperkalaemia) and sheep (MCC). KEY RESULTS: In vitro, NVP-QBE170 potently
      inhibited ENaC function in HBEC and showed a longer duration of action to
      comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170
      attenuated ENaC activity in the guinea pig airways with greater potency and
      duration of action than that of amiloride without inducing hyperkalaemia in
      either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep
      increased MCC and was better than inhaled hypertonic saline in terms of efficacy
      and duration of action. CONCLUSIONS AND IMPLICATIONS: NVP-QBE170 highlights the
      potential for inhaled ENaC blockers to exhibit efficacy in the airways with a
      reduced risk of hyperkalaemia, relative to existing compounds.

PMID- 25573197
TI  - Immunotoxicological effects of streptozotocin and alloxan: in vitro and in vivo
      studies.
AB  - Streptozotocin (STZ) and alloxan (ALX), widely used to induce diabetes in
      experimental animals, have different structures and mechanisms of action. We
      investigated those effects of these drugs on the immune system that might
      influence engraftment efficiency and graft survival in transplantation models,
      and their cytotoxicity on hematopoietic cell lines. We used the minimum dose to
      induce diabetes in a mouse, i.e. 180 mg/kg i.v. STZ and 75 mg/kg i.v. ALX. Both
      groups exhibited significant decrease in body weight during 4 days post-treatment
      as compared to controls. We found that blood glucose in ALX-injected mice
      increased faster than in STZ-injected mice. The total number of recovered
      splenocytes was lower in STZ-injected animals than in ALX-injected animals. The
      survival periods of rat islet grafts in recipient mice were longer and more
      diverse in STZ-injected recipients (7-24 days) compared to ALX-injected
      recipients (6-7 days). The in vitro study showed that ALX was less cytotoxic in
      cell lines with IC50 values of 2809, 3679 and >4000 MUg/ml for HL60, K562 and
      C1498 cells respectively. STZ was more toxic, especially in HL60 cells, with IC50
      values of 11.7, 904 and 1024 MUg/ml for HL60, K562 and C1498 cells respectively.
      Furthermore, in response to concanavalin A (Con-A), splenocytes from STZ-injected
      mice produced higher amounts of interferon-gamma (IFN-gamma) than those from ALX
      injected mice. In conclusion, STZ was more cytotoxic than ALX in vitro and in
      vivo. STZ caused lymphocytopenia, which may result in longer graft survival in
      STZ-treated animals than in ALX-treated animals.

PMID- 25573196
TI  - Linkage disequilibrium network analysis (LDna) gives a global view of chromosomal
      inversions, local adaptation and geographic structure.
AB  - Recent advances in sequencing allow population-genomic data to be generated for
      virtually any species. However, approaches to analyse such data lag behind the
      ability to generate it, particularly in nonmodel species. Linkage disequilibrium
      (LD, the nonrandom association of alleles from different loci) is a highly
      sensitive indicator of many evolutionary phenomena including chromosomal
      inversions, local adaptation and geographical structure. Here, we present linkage
      disequilibrium network analysis (LDna), which accesses information on LD shared
      between multiple loci genomewide. In LD networks, vertices represent loci, and
      connections between vertices represent the LD between them. We analysed such
      networks in two test cases: a new restriction-site-associated DNA sequence (RAD
      seq) data set for Anopheles baimaii, a Southeast Asian malaria vector; and a well
      characterized single nucleotide polymorphism (SNP) data set from 21 three-spined
      stickleback individuals. In each case, we readily identified five distinct LD
      network clusters (single-outlier clusters, SOCs), each comprising many loci
      connected by high LD. In A. baimaii, further population-genetic analyses
      supported the inference that each SOC corresponds to a large inversion,
      consistent with previous cytological studies. For sticklebacks, we inferred that
      each SOC was associated with a distinct evolutionary phenomenon: two chromosomal
      inversions, local adaptation, population-demographic history and geographic
      structure. LDna is thus a useful exploratory tool, able to give a global overview
      of LD associated with diverse evolutionary phenomena and identify loci
      potentially involved. LDna does not require a linkage map or reference genome, so
      it is applicable to any population-genomic data set, making it especially
      valuable for nonmodel species. 

PMID- 25573198
TI  - Effect of premedications in a murine model of asparaginase hypersensitivity.
AB  - A murine model was developed that recapitulates key features of clinical
      hypersensitivity to Escherichia coli asparaginase. Sensitized mice developed high
      levels of anti-asparaginase IgG antibodies and had immediate hypersensitivity
      reactions to asparaginase upon challenge. Sensitized mice had complete inhibition
      of plasma asparaginase activity (P = 4.2 * 10(-13)) and elevated levels of mouse
      mast cell protease 1 (P = 6.1 * 10(-3)) compared with nonsensitized mice. We
      investigated the influence of pretreatment with triprolidine, cimetidine, the
      platelet activating factor (PAF) receptor antagonist CV-6209 [2-(2-acetyl-6
      methoxy-3,9-dioxo-4,8-dioxa-2,10-diazaoctacos-1-yl)-1-ethyl-pyridinium chloride],
      or dexamethasone on the severity of asparaginase-induced allergies. Combining
      triprolidine and CV-6209 was best for mitigating asparaginase-induced
      hypersensitivity compared with nonpretreated, sensitized mice (P = 1.2 * 10(-5)).
      However, pretreatment with oral dexamethasone was the only agent capable of
      mitigating the severity of the hypersensitivity (P = 0.03) and partially
      restoring asparaginase activity (P = 8.3 * 10(-4)). To rescue asparaginase
      activity in sensitized mice without requiring dexamethasone, a 5-fold greater
      dose of asparaginase was needed to restore enzyme activity to a similar
      concentration as in nonsensitized mice. Our results suggest a role of histamine
      and PAF in asparaginase-induced allergies and indicate that mast cell-derived
      proteases released during asparaginase allergy may be a useful marker of clinical
      hypersensitivity. 

PMID- 25573199
TI  - Molecular regulation of the expression of leptin by hypoxia in human coronary
      artery smooth muscle cells.
AB  - BACKGROUND: Leptin, produced mainly by white adipose tissue, is a hormone that
      promotes vascular smooth muscle cell (VSMC) migration and proliferation, a
      process involved in the pathophysiology of atherosclerosis. Leptin expression in
      human coronary artery smooth cell (HCASMC) is induced by hypoxia. However, our
      understanding of the process of atherosclerosis in HCASMC is only emerging. Since
      the mechanisms by which hypoxia regulates leptin in HCASMC are as yet unknown,
      this study aims to investigate the mechanics of molecular regulation of leptin
      expression in HCASMC under hypoxia. We subjected cultured HCASMCs to hypoxia for
      varying periods of time. Through use of different signal pathway inhibitors, we
      were able to sort out and identify the pathway through which hypoxia-induced
      leptin expression occurs. RESULTS: Leptin mRNA and protein levels increased after
      2.5% hypoxia for 2-to-4 hours, with earlier expression of angiotensin II (AngII)
      and reactive oxygen species (ROS). The addition before hypoxia of the c-Jun N
      terminal kinase (JNK) pathway inhibitor (SP600125), JNK small interfering RNA
      (siRNA), AngII receptor blockers (ARBs; losartan), or N-acetyl-L-cysteine (NAC,
      an ROS scavenger), had the effect of inhibiting JNK phosphorylation and leptin
      expression. Gel shift assay and luciferase promoter study showed that
      leptin/activator protein 1 (AP-1) binding and transcriptional activity to the
      leptin promoter increased after hypoxia, and SP600125, JNK siRNA, losartan, and
      NAC abolished the binding and transcriptional activity induced by hypoxia. The
      use of SP600125, JNK siRNA, losartan, and NAC effectively inhibited the binding
      and transcriptional activity induced by hypoxia. Migration and proliferation, ROS
      generation, and the presence of leptin in the nuclei of HCASMCs also increased
      under hypoxia. CONCLUSION: Hypoxia in HCASMCs increases leptin expression through
      the induction of AngII, ROS, and the JNK pathway to enhance atherosclerosis in
      HCASMCs.

PMID- 25573200
TI  - Cytotoxicity associated with electrospun polyvinyl alcohol.
AB  - Polyvinyl alcohol (PVA) is a synthetic, water-soluble polymer, with applications
      in industries ranging from textiles to biomedical devices. Research on
      electrospinning of PVA has been targeted toward optimizing or finding novel
      applications in the biomedical field. However, the effects of electrospinning on
      PVA biocompatibility have not been thoroughly evaluated. In this study, the
      cytotoxicity of electrospun PVA (nPVA) which was not crosslinked after
      electrospinning was assessed. PVA polymers of several molecular weights were
      dissolved in distilled water and electrospun using the same parameters.
      Electrospun PVA materials with varying molecular weights were then dissolved in
      tissue culture medium and directly compared against solutions of nonelectrospun
      PVA polymer in human coronary artery smooth muscle cells and human coronary
      artery endothelial cells cultures. All nPVA solutions were cytotoxic at a
      threshold molar concentration that correlated with the molecular weight of the
      starting PVA polymer. In contrast, none of the nonelectrospun PVA solutions
      caused any cytotoxicity, regardless of their concentration in the cell culture.
      Evaluation of the nPVA material by differential scanning calorimetry confirmed
      that polymer degradation had occurred after electrospinning. To elucidate the
      identity of the nPVA component that caused cytotoxicity, nPVA materials were
      dissolved, fractionated using size exclusion columns, and the different fractions
      were added to HCASMC and human coronary artery endothelial cells cultures. These
      studies indicated that the cytotoxic component of the different nPVA solutions
      were present in the low-molecular-weight fraction. Additionally, the amount of
      PVA present in the 3-10 kg/mol fraction was approximately sixfold greater than
      that in the nonelectrospun samples. In conclusion, electrospinning of PVA
      resulted in small-molecular-weight fractions that were cytotoxic to cells. This
      result demonstrates that biocompatibility of electrospun biodegradable polymers
      should not be assumed on the basis of success of their nonelectrospun
      predecessors.

PMID- 25573201
TI  - Absolute lymphocyte count as predictor of overall survival for patients with
      multiple myeloma treated with single autologous stem cell transplant.
AB  - Post-autologous stem cell transplant (ASCT) studies have demonstrated that
      absolute lymphocyte count (ALC) recovery is associated with prolonged survival in
      some hematological malignancies. To assess whether ALC recovery has prognostic
      significance in patients with multiple myeloma (MM) undergoing single ASCT, we
      conducted a retrospective analysis of ALC at different time-points in patients
      with MM. In total 769 consecutive patients who underwent single ASCT from January
      2000 to December 2007 were evaluated. An ALC of >= 1400 cells/MUL at day 0, day
      15 and day 90 significantly correlated with a better overall survival (OS)
      (median OS of 111, 90.7 and 84 months vs. 74, 70.5 and 65 months, respectively, p
      < 0.001 for all time-points). Multivariate analysis showed that ALC is an
      independent prognostic factor for OS after ASCT. In conclusion, ALC is a
      surrogate marker of the host immune system that correlates with better survival
      in patients with MM undergoing single ASCT. Immunomodulatory drugs, vaccination
      strategies and cellular therapies in MM should be investigated. 

PMID- 25573202
TI  - Point mutations in TP53 but not in p15(Ink4b) and p16(Ink4a) genes represent poor
      prognosis factors in acute adult T cell leukemia/lymphoma.

PMID- 25573203
TI  - Immunohistochemical expression of cell cycle proteins in multiple myeloma.

PMID- 25573204
TI  - Serum YKL-40: a new independent prognostic marker for skeletal complications in
      patients with multiple myeloma.
AB  - In a time of increasing treatment options for multiple myeloma bone disease, risk
      factors predicting progression need to be elucidated. This study investigated the
      value of serum YKL-40, previously shown to be associated with radiographic
      progression of bone destruction, as a predictor for time to clinical progression,
      i.e. skeletal-related events (SREs), in 230 newly diagnosed patients with
      multiple myeloma receiving intravenous bisphosphonates. Serum concentrations of
      YKL-40 and biochemical bone markers (CTX-MMP, CTX-I, PINP) were measured at
      diagnosis. Patients were evaluated every third month for SRE and at 9 and 24
      months for radiographic progression. Elevated serum YKL-40 was seen in 47% of
      patients and associated with high-risk disease (International Staging System
      stage III; p < 0.001), increased bone resorption (serum CTX/MMP; p < 0.001) and
      early radiographic progression at 9 months (p = 0.01). Serum YKL-40 together with
      serum CTX-MMP/PINP ratio and World Health Organization status were independent
      predictors of time to first SRE. 

PMID- 25573206
TI  - Clinical significance of quantitative monitoring and mutational analysis of BCR
      ABL1 transcript in Philadelphia chromosome positive B lymphoblastic leukemia.
AB  - Quantitative detection of BCR-ABL1 transcript is essential in monitoring residual
      disease of Philadelphia chromosome positive B lymphoblastic leukemia (Ph+ B-LL).
      We studied the kinetics of BCR-ABL1 transcript in 41 Ph+ B-LL patients in
      correlation with their clinical outcome. A total of 23 patients achieved complete
      molecular remission at 6 months post-treatment. This was associated with a lower
      relapse risk and better overall survival. Likewise, sustainable complete
      molecular remission in 27 patients was associated with superior clinical outcome.
      Sporadic low level BCR-ABL1 was detected in 12 of 27 patients who had attained
      complete molecular remission. The relapse rate was significantly higher in non
      transplant patients with persistent positive BCR-ABL1 than patients transplanted
      when BCR-ABL1 was detectable. All eight patients harboring ABL1 kinase domain
      mutations died of disease or were transferred to hospice care. We concluded that
      monitoring the level of BCR-ABL1 transcript after hematologic remission has
      predictive value to the long-term outcome.

PMID- 25573205
TI  - Prognostic effect of Ki-67 expression in rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisone-treated diffuse large B-cell lymphoma is
      limited to non-germinal center B-cell-like subtype in late-elderly patients.
AB  - This study evaluated the effect of age and cell of origin on the prognostic
      significance of Ki-67 labeling index (Ki-67 LI) on overall survival (OS) of
      diffuse large B-cell lymphoma (DLBCL) in a cohort of 697 patients treated with
      rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R
      CHOP). Multivariate analysis revealed no prognostic significance of high Ki-67 LI
      (>= 85%) for OS. However, on subgroup analysis, high Ki-67 LI was significantly
      associated with poor OS in late-elderly patients (aged >= 70 years) (p = 0.021)
      and non-germinal center B-cell-like (GCB) subtype (p = 0.015). In particular,
      high Ki-67 LI was associated with a poor prognosis in late-elderly patients with
      non-GCB subtype. No correlation was observed in young adults (aged < 60 years) or
      early-elderly (aged 60-70 years) patients or GCB subtype. The present study shows
      that high Ki-67 LI is a risk factor for poor OS in the late-elderly age group and
      non-GCB subtype in patients with DLBCL treated with R-CHOP. 

PMID- 25573207
TI  - Case of Behcet's disease complicated by oculomotor nerve palsy associated with
      internal carotid artery-posterior communicating artery aneurysm.
AB  - Behcet's disease (BD) is a relapsing systemic inflammatory disorder of unknown
      etiology involving systemic vasculitis. Vasculitis in BD results from the
      involvement of arteries, veins and blood vessels of all sizes, which leads to the
      three major manifestations of this condition: venous occlusion, arterial
      occlusion and aneurysm formation. Therefore, whole-body vascular involvement
      should always be considered in BD patients. Here, we describe the first
      appearance of an internal carotid-posterior communicating artery aneurysm,
      resulting in complete oculomotor nerve palsy in a BD patient. A 44-year-old
      Japanese man suffered from recurrent episodes of erythema nodosum that had
      presented on the lower extremities for the past 2 years. His condition was
      diagnosed as an incomplete type of BD based on relapsing oral and genital ulcers,
      skin eruptions, such as erythema nodosum and folliculitis, a positive pathergy
      test and systemic arthralgia. Ten years after his initial clinical presentation,
      he had manifestations of right-sided ptosis and cyclic dull pain in his right
      temporal region. Magnetic resonance imaging and angiography revealed a right
      internal carotid artery-posterior communicating artery aneurysm. Although
      oculomotor nerve palsy associated with internal carotid artery-posterior
      communicating artery aneurysm in a BD patient has not been reported previously,
      our report highlights the fact that this abnormal manifestation should be
      considered in those with vasculo-BD.

PMID- 25573208
TI  - How do I implement a more restrictive transfusion trigger of hemoglobin level of
      7 g/dL at my hospital?
AB  - BACKGROUND: The red blood cell (RBC) transfusion trigger is a major driver of
      transfusion practice and affects health care costs and in some instances patient
      outcomes. Reducing the transfusion threshold will decrease RBC utilization and
      hospital costs. STUDY DESIGN AND METHODS: The hospital transfusion committee,
      endorsed by the medical staff executive committee, developed an educational
      program for physicians, nurses, and blood bank staff focusing on the scientific
      basis for a transfusion trigger of hemoglobin (Hb) of 7 g/dL rather than 8 g/dL
      as well as a program to discourage the routine 2-unit RBC transfusion. RBC
      transfusion practice review was performed and those physicians transfusing
      outside of the new variables were questioned as to the necessity for the
      transfusion. RESULTS: A total of 4492 RBC units were saved and 662 patients were
      not transfused over the three fiscal years (FYs), 2010, 2011, and 2012, compared
      to 2009 baseline. Direct cost savings over 3 years with a transfusion trigger of
      Hb of 7 g/dL was $943,320. If activity-based costing is used, the savings may
      have reached as high as $5,314,036. The number of single-unit RBC transfusions
      increased steadily over the course of the study while the number of 2-unit
      transfusions remained relatively stable over the three FYs 2010 to 2012.
      CONCLUSION: A Hb level of 7 g/dL is the transfusion threshold which is being
      adopted by many hospitals. Institutional culture change to a Hb level of 7 g/dL
      can be implemented with the right champion when endorsed by upper echelon medical
      leadership and hospital administration.

PMID- 25573210
TI  - [Surgical treatment of congenital vascular ring].
AB  - OBJECTIVE: To discuss the diagnosis and surgical treatment of congenital vascular
      ring and prognostic factors. METHODS: The clinic data of 42 cases of congenital
      vascular from January 2010 to December 2013 was analyzed retrospectively
      (accounting for 1.04% congenital heart operations over the same period ). There
      were 26 male and 16 female patients, aged at surgery 24 days to 6 years (average
      10.7 months). The diagnosis including pulmonary artery sling in 26 cases, double
      aortic arch in 10 cases, right aortic arch with aberrant left subclavian artery
      in 3 cases, pulmonary artery sling and right aortic arch with vagus left
      subclavian artery in 2 cases, pulmonary artery sling and left aortic arch with
      vagus right subclavian artery in 1 case. In addition to 4 cases the remaining 38
      patients were still combined with other cardiovascular malformations. Thirty-six
      cases of children underwent spiral CT airway remodeling, 23 children underwent
      fiber- bronchoscopy. In addition to 2 cases of airway abnormalities not seen, the
      rest of the children were present in varying degrees in different parts of
      tracheal stenosis or tracheomalacia. All patients underwent surgical correction
      of congenital vascular ring, concomitant heart deformity correction surgery
      according to the situation (7 cases of atrial septal defect repair, 3 of
      ventricular septal defect repair, 1 of mitral valvuloplasty, 1 of bi-Glenn, 1 of
      coarctation of the aorta correction with ventricular septal defect repair, 1 of
      trilogy of Fallot correction). One case suffered resection of tracheal stenosis
      and Slide tracheoplasty simultaneously, another case was implanted tracheal
      stenting postoperatively after pulmonary artery sling correction. RESULTS: Three
      patients died in hospital (7.1%), the cause of death were recurrent granuloma
      formation postoperatively. Remaining 39 patients were successfully discharged.
      The median time of overall survival of children with mechanical ventilation was
      14 h (22 h) (M (Q(R))), median ICU residence time was 5 d (8 d), and the median
      in-hospital time was 19 d (9 d). Tracheal intubation time and postoperative ICU
      duration time in children with pulmonary artery sling children were much more
      than in children with double aortic arch (23 h (123 h) vs. 9 h(9 h), 7 d (13 d)
      vs. 4 d (2 d)), but the difference were not statistically significant. There was
      significant difference in the duration of hospitalization between the patient
      with the pulmonary artery sling and double aortic arch (23 d (9 d) vs. 16 d(6 d))
      (chi(2) = 10.157, P = 0.006). CONCLUSIONS: The recent results of surgical
      treatment of congenital vascular ring is safe and effective. The extent and scope
      of tracheal stenosis and tracheomalacia is a critical influence prognosis.

PMID- 25573211
TI  - [The clinical application value of dual source CT quantification volume imaging
      to forecast lung cancer patients' postoperative pulmonary function changing: a
      prospective study].
AB  - OBJECTIVE: To probe the clinical application and value of dual source CT
      quantification volume imaging to forecast lung cancer patients' postoperative
      pulmonary function changing. METHODS: Between June 2012 and June 2013, there were
      233 patients (121 male patients and 112 female patients, with a mean age of (53
      +/- 16) years) who accepted the thoracoscope lobectomy or unilateral holo-lungs
      pneumonectomy accepted pulmonary function test before and after 3 months of the
      surgery. CT scan was conducted at both inspiration phase and expiration phase
      before the surgery and the lung volume of the single lobe, the pixel exponential
      distribution histogram, and the average lung density were measured after CT scan.
      The discrepancy and correlation between the preoperative lung volume accepted by
      CT and preoperative, postoperative pulmonary function index were compared.
      RESULTS: The CT volume scan showed that average lung density of the superior part
      at decubitus position is -(870 +/- 22) HU, the inferior part was -(767 +/- 16) HU
      (t = 3.13, P < 0.01). The volume ratio of the right upper lobe, right middle
      lobe, right lower lobe, left upper lobe, left lower lobe were 20.5%, 10.3%,
      23.1%, 24.6%, 21.5%, whole-right lung was 53.9% and whole-left was 46.1%. There
      were high correlation between CT volume index and preoperative routine pulmonary
      function index such as total lung capacity, forced vital capacity (FVC), forced
      expiratory volume in the first second (FEV(1)), residual volume, and FEV(1)/FVC.
      The highest correlation coefficient were 0.92, 0.76, 0.70, 0.85, 0.56 (t = 3.14,
      3.05, 2.86, 3.09, 2.68; all P < 0.01). The highest correlation coefficient for
      the postoperative pulmonary function index were 0.87, 0.68, 0.75, 0.81, -0.64 (t
      = 3.10, 2.85, 3.05, 3.02, 2.79; all P < 0.01). CONCLUSIONS: It is feasible to use
      dual source CT quantification volume imaging to predict lung cancer patients'
      postoperative pulmonary function alteration, which can provide precise predictive
      value of these patients. CT quantification volume imaging technology has
      important clinical application value.

PMID- 25573212
TI  - [Effect of intervertebral disc degeneration on spinal flexibility in patients
      with degenerative lumbar scoliosis].
AB  - OBJECTIVE: To investigate degenerative changes of the intervertebral disc and
      their impact on spinal flexibility in patients with degenerative lumbar scoliosis
      (DLS). METHODS: Retrospective analysis of 66 patients (average age 58.4 years, 10
      males and 56 females) with DLS was conducted from May 2008 to February 2014. For
      all patients, pre-operative standing X-ray film, Bending X-ray films and
      thoracolumbar MRI were taken. Cobb's angle was measured in each X-ray film and
      intervertebral angle was measured in both standing and Bending X-ray films. All
      discs were graded according to Pfirrmann degeneration grades on T2 weighted
      saggital MRI imaging. Statistical analyses were performed to determine the
      correlation between intervertebral disc degeneration with the whole spine
      flexibility and segmental flexibility. RESULTS: For all 66 subjects, the average
      Cobb's angle of pre-operative and bending X-ray film was 36 degrees  +/- 13
      degrees , 21 degrees  +/- 11 degrees , respectively. The average flexibility was
      45% +/- 15% in our study. Totally 268 discs were graded, including gradeI8, II
      68, III 83, IV 91, V 18. In the main curve, there was significant correlation
      between the average degree of disc degeneration and the whole spine flexibility(r
      = -0.727, P < 0.01). There was significant correlation between the grade of
      segmental disc degeneration and segmental flexibility (P < 0.01) . The apical
      intervertebral disc had the most degeneration (P < 0.01) and worst flexibility (P
      < 0.01) , compared with other discs in the main curve. CONCLUSIONS: The degree of
      intervertebral disc degeneration is closely correlated with spinal flexibility in
      DLS. The more the disc degeneration is, the worse the spinal flexibility becomes.

PMID- 25573209
TI  - Corticotropin releasing hormone and imaging, rethinking the stress axis.
AB  - The stress system provides integration of both neurochemical and somatic
      physiologic functions within organisms as an adaptive mechanism to changing
      environmental conditions throughout evolution. In mammals and primates the
      complexity and sophistication of these systems have surpassed other species in
      triaging neurochemical and physiologic signaling to maximize chances of survival.
      Corticotropin releasing hormone (CRH) and its related peptides and receptors have
      been identified over the last three decades and are fundamental molecular
      initiators of the stress response. They are crucial in the top down regulatory
      cascade over a myriad of neurochemical, neuroendocrine and sympathetic nervous
      system events. From neuroscience, we've seen that stress activation impacts
      behavior, endocrine and somatic physiology and influences neurochemical events
      that one can capture in real time with current imaging technologies. To delineate
      these effects one can demonstrate how the CRH neuronal networks infiltrate
      critical cognitive, emotive and autonomic regions of the central nervous system
      (CNS) with somatic effects. Abundant preclinical and clinical studies show inter
      regulatory actions of CRH with multiple neurotransmitters/peptides. Stress, both
      acute and chronic has epigenetic effects which magnify genetic susceptibilities
      to alter neurochemistry; stress system activation can add critical variables in
      design and interpretation of basic and clinical neuroscience and related
      research. This review will attempt to provide an overview of the spectrum of
      known functions and speculative actions of CRH and stress responses in light of
      imaging technology and its interpretation. Metabolic and neuroreceptor positron
      emission/single photon tomography (PET/SPECT), functional magnetic resonance
      imaging (fMRI), anatomic MRI, diffusion tensor imaging (DTI), and proton magnetic
      resonance spectroscopy (pMRS) are technologies that can delineate basic
      mechanisms of neurophysiology and pharmacology. Stress modulates the myriad of
      neurochemical and networks within and controlled through the central and
      peripheral nervous system and the effects of stress activation on imaging will be
      highlighted. 

PMID- 25573213
TI  - [Measurement and comparison of postoperative anterior cord space between C2-7 and
      C3-7 laminoplasty on MRI].
AB  - OBJECTIVES: To investigate the effect of C(2-7) laminoplasty on postoperative
      anterior cord space (ACS) compared with C(3-7) laminoplasty, and to provide
      evidence for reasonable enlargement of decompression range cephalad. METHODS:
      Fifty-seven Patients underwent cervical laminoplasty from February 2008 to
      October 2011 were studied retrospectively, which were divided into two groups by
      decompression range: Group C(3-7) and Group C(2-7). The pre-and post operative
      JOA scores,VAS scores of neek and shoulder pain, and cervical alignment were
      compared in each group. The postoperative ACS at each level from C(2-3) to C(7)
      T(1) measured on MRI were compared between the two groups. RESULTS: The
      postoperative JOA scores increased significantly in both groups. VAS scores and
      cervical alignment showed no significant difference. ACS at C(2-3) and C(3-4) was
      6.13 mm (95%CI: 5.71-6.55) and 6.60 mm (95%CI: 6.10-7.11) respectively in Group
      C(3-7), which increased 2.5 mm and 2.1 mm respectively in Group C2-7 at the same
      segment, there was significant difference (P < 0.01). However, there was no
      significant difference of ACS at C(4-5) and any other caudal levels between the
      two groups. CONCLUSIONS: Compared with conventional C(3-7) laminoplasty, the
      extensive decompression cephalad to C(2) leads to larger ACS at C(2-3) and C(3
      4). When the mid-sagittal diameter of anterior compression is more than 6.10 mm
      at C(3-4), C(3-7) laminoplasty may cause insufficient decompression, and
      enlargement of decompression range cephalad should be considered.

PMID- 25573214
TI  - [Clinical application of a novel posterior lumbar fusion method and the short
      term observation of its effect].
AB  - OBJECTIVE: To increase local blood supply of bone graft, a novel posterior lumbar
      spine fusion method with orthotopic paraspinal muscle-pediculated bone flaps was
      constructed, and the fusion rate and clinical effect.were observed. METHODS: From
      June 2007 to December 2010, 117 patients of lumbar spinal stenosis or lumbar
      destabilization treated with the novel posterior lumbar fusion method were
      studied, 49 males and 68 females, aged from 40 to 77 years, average 61.5 years.
      Clinical effect was evaluated by JOA and VAS score preoperatively and
      postoperatively, and the fusion result was evaluated by three-dimensional CT
      reconstruction postoperatively. RESULTS: Seventeen cases lost of follow up, the
      rest were followed up from 7 to 38 months, average 19 months. There was
      significant difference between pre- and postoperative JOA and VAS score (P <
      0.01), the preoperative JOA score was 10.3 +/- 1.9, and 25.4 +/- 4.2 at the
      latest follow-up, the improvement rate was 81.0% ; the preoperative VAS score was
      8.5 +/- 0.8, and 2.3 +/- 0.4 at the latest follow-up. The three-dimensional CT
      reconstruction showed that 126 of the 133 segments formed solid fusion in 100
      patients who completed the follow-up, the fusion rate was 94.7%. CONCLUSION: The
      novel posterior lumbar fusion method make the bone graft position more precise,
      stable and increases the fusion rate, which can effectively reduce pseudarthrosis
      and have a promising clinical effect.

PMID- 25573215
TI  - [Reimplantation of devitalized tumor-bearing bone in pelvic reconstruction after
      en-bloc tumor resection].
AB  - OBJECTIVE: To analyze the clinical outcome of an operative technique using
      recycling bones to reconstruct pelvis after primary malignant pelvic tumor
      resection. METHODS: Fifteen patients who presented with malignant pelvic tumors
      were treated by wide or marginal resection and reconstruction using recycling
      bone in our institute from January 2003 to December 2011. The median age was 31
      (15-62) years, and the most common diagnosis was chondrosarcoma, followed by
      Ewing sarcoma. The operative technique consisted of en-bloc excision of the
      pelvic tumor, removal of soft tissue, curettage of the tumor, incubated in 65 
      degrees C 20% hypertonic saline for 30 minutes, reimplantation of recycling bone,
      and internal fixation with plates, screws and/or total hip replacement. Bone
      cement was used to augment bone strength when necessary. Bone healing features
      and function of lower limbs were evaluated with the International Society of Limb
      Salvage (ISOLS) graft evaluation method and Musculoskeletal Tumor Society (MSTS)
      score, respectively. Adjuvant therapies were used according to the type and
      extension of the primary tumor. RESULTS: One patient died of severe peri
      operative bleeding 2 days after operation, and the other patients were followed
      up for 6 to 96 months (mean 40.4 months), and 5 patients died of local recurrence
      or metastasis. Eleven operations were followed by complications of any kind. Most
      mechanical complications were related to the use of hip arthroplasties, where
      implant breakdown and dislocation were the commonest.Infection was seen in 7
      cases (superficial 4 cases and deep 3 cases). Healing and functional scores were
      fair. The median ISOLS score and MSTS score were 81.0% (range 30.0% to 95.0%) and
      60.0% (range 23.0% to 93.0%), respectively. CONCLUSIONS: Recycling reconstruction
      technique is valid for young patients with low-grade chondrosarcoma or other
      chemo-sensitive tumor in pelvis. Although many complications are seen, this
      method remains our treatment of choice.

PMID- 25573216
TI  - [Continuous observation of changes in renal function after radical nephrectomy].
AB  - OBJECTIVE: To evaluate continuous change in renal function by various clinical
      factors after radical nephrectomy (RN). METHODS: Patients after RN from January
      2007 to December 2011 in the First Affiliated Hospital to Soochow University were
      enrolled, 356 cases continuously enrolled throughout the follow-up process,
      because of lost, missing data and other material reasons, 185 cases meet the
      requirements, eventually, including 121 male and 64 female patients, aged from 30
      to 88 years (average age: (58 +/- 12) years). There were 34 diabetes mellitus, 82
      hypertension patients. Open surgery for 132 cases, laparoscopic surgery for 53
      cases. Continuous checked serum creatinine at 3, 6, 9, 12, 24, 36, 48, 60, 72
      months after RN and calculated to estimated glomerular filtration rate (eGFR) by
      Modification of Diet in Renal Disease equation.Linear mixed models were carried
      out to analyze postoperative continuous change in eGFR in multivariate regression
      analysis postoperative risk factors for changes in renal function. RESULTS:
      Overall, there was a subsequent restoration of renal function over the follow-up
      period. The slope (beta) for the relationship between the eGFR and the time since
      RN was 0.099 (95%CI:0.07-0.13, P < 0.01) indicating that each month after RN was
      associated with an increase in eGFR of 0.099 ml*min(-1)*(1.73 m(2))(-1)*month(
      1). The slope (beta) was different between the group with clinical factor and its
      reference group, but the difference in the next three groups with statistically
      significant after multivariate regression analysis:diabetic and non-diabetic
      mellitus patients with a slope (beta) of -0.02 and 0.12 (P < 0.01) .Hypertension
      and non-hypertensive patients with a slope (beta) of 0.08 and 0.11 (P < 0.05).
      Age <= 50 years, > 50-65 years and > 65 years patients with a slope (beta) of
      0.15,0.09 and 0.05 (P < 0.05), respectively. There were 13 new-onset of chronic
      kidney disease (CKD) after RN, including 9 patients with CKD III and 4 patients
      with CKD IV. CONCLUSIONS: Renal function recover continuously during the follow
      up period after RN. Preoperative predictors of an increase in eGFR after RN are
      young age, no diabetes mellitus, no hypertension.

PMID- 25573217
TI  - [Outcomes and predictors of T3a prostate cancer treated by permanent interstitial
      brachytherapy combined with external radiotherapy and hormone therapy].
AB  - OBJECTIVE: To evaluate the outcomes of T3a prostate cancer treated by permanent
      interstitial brachytherapy combined with external radiotherapy and hormone
      therapy, and analyse the influence of preoperative factors on prognosis. METHODS:
      From January 2003 to December 2008, 38 pactients with T3a prostate cancer aged
      from 48 to 81 years (mean: 71 years) were enrolled, with serum prostate specific
      antigen (PSA) levels ranged from 10.000 to 99.800 ug/L (mean: 56.300 ug/L),
      Gleason score from 5 to 9 (mean: 7.6) and percentage of positive biopsy cores
      from 10.0% to 100% (mean: 65.3%). All patients were treated by permanent
      interstitial brachytherapy combined with external radiotherapy and hormone
      therapy. Survival curves were calculated using the Kaplan-Meier method. The
      predictive factors including patient's age, prostate volume, serum pre-treatment
      PSA, Gleason score and percentage of positive biopsy cores were used for
      univariate analysis on biochemical failure-free, distant metastasis-free and
      overall survival. RESULTS: The mean follow-up was 69 months (range: 9-109
      months).Nineteen patients experienced biochemical failure. The average
      biochemical failure time was 13.4 months (range: 1-40 months). There were 13
      patients developed as distant metastatic prostate cancer since average 19.7
      months (range: 1-70 months) after brachytherapy. Of all patients, 9 died of
      prostate cancer recurrence, while 6 passed away because of other reasons, with an
      average of 52.2 months (range: 9.0- 98.5 months). The 5-year biochemical failure
      free survival (BFFS), distant metastasis free survival (DMFS), cancer specific
      survival (CSS) and overall survival (OS) rate were 44.1%, 68.6%, 82.4 and 75.8%,
      respectively. Twenty-nine patients experienced grade 1-2 gastrointestinal
      toxicity and 18 patients experienced grade 1-2 genitourinary toxicity. In
      univariate analysis, the percentage of positive biopsy cores was significantly
      correlated with BFFS (chi(2) = 17.240, P = 0.000), DMFS (chi(2) = 18.641, P =
      0.000) and OS (chi(2) = 8.970, P = 0.003); the Gleason score was significantly
      correlated with DMFS (chi(2) = 12.484, P = 0.000) and OS (chi(2) = 6.575, P =
      0.010); and patient's age was significantly correlated with OS (chi(2) = 5.179, P
      = 0.023). CONCLUSIONS: Permanent interstitial brachytherapy combined with
      external radiotherapy and hormone therapy is alternative for T3a prostate cancer.
      The percentage of positive biopsy cores is correlated with BFFS, DMFS and OS.

PMID- 25573219
TI  - [Experimental study on concentrations and pharmacokinetics of antibiotics in bile
      and evaluation of their microbicidal potential].
AB  - OBJECTIVE: To study the concentrations and pharmacokinetics of 6 different kinds
      of antibiotics in rabbit bile, and evaluate their microbicidal potential.
      METHODS: Thirty-six health rabbits were randomly divided into 6 groups, and each
      group was 6 rabbits. After anaesthesia, the common bile duct of rabbit was
      isolated and cumulated with a silicone tube. The rabbits were administered
      intravenously with the equal-effect dose of antibiotics. Bile (1.5 ml) was
      collected at different time points after administration, and the concentration of
      antibiotics of bile was assayed by high performance liquid chromatography. The
      bile drug concentration-time data were processed by software to figure out the
      pharmacokinetic parameters such as maximum concentration (C(max)), peak time
      (T(max)), half-life time (T(1/2)), clearance (CL) and apparent volume of
      distribution (VD). The bile antibiotics concentration contrasted to the minimum
      inhibitory concentration (MIC), and attained the bactericidal index (C(max)/MIC)
      and the time when the drug concentration exceeded the MIC (T(>MIC)). RESULTS: The
      C(max) and T1/2 of each antibiotic were as the followings: piperacillin (7 950 +/
      3 023) mg/L and (1.97 +/- 1.23) h, ceftriaxone (1 104 +/- 248) mg/L and (3.14 +/
      0.57) h, cefoperazone (5 215 +/- 2 225) mg/L and (0.89 +/- 0.13) h, meropenem
      (31.97 +/- 12.44) mg/L and (0.36 +/- 0.11) h, levofloxacin (66.3 +/- 36.9) mg/L
      and (3.32 +/- 2.57) h, metronidazole (28.2 +/- 10.2) mg/L and (0.81 +/- 0.33) h,
      respectively. Piperacillin/tazobactam and cefoperazone/sulbactam had the largest
      bactericidal index and the longest T(>MIC), and their bactericidal indexes were
      (62.1 +/- 23.6) - (993.8 +/- 377.9) and (164.8 +/- 69.0) - (659.3 +/- 275.9),
      their T(>MIC) were (6.00 +/- 2.53) - (8.00 +/- 0.00) h and (6.33 +/- 1.97) -
      (8.00 +/- 0.00) h. The bactericidal index and T(>MIC) of levofloxacin were the
      smallest, which were (2.1 +/- 1.2) - (8.3 +/- 4.6) and (0.54 +/- 0.25) - (2.67 +/
      1.03) h . Ceftriaxone and meropenem were as the medium, and their bactericidal
      indexes and T(>MIC) were (4.3 +/- 1.0) - (69.2 +/- 15.5) , (1.42 +/- 0.65) -
      (8.00 +/- 0.00) h and (2.0 +/- 0.8) - (1 031.3 +/- 401.4) , (0.29 +/- 0.10) -
      (1.83 +/- 0.26) h. The bactericidal index of metronidazole to anaerobic ranged
      from 7.4 to 294.9, and the T(>MIC) ranged from 1.88 to 5.00 h. CONCLUSIONS: The
      bile concentrations of six antibiotics all exceed their effective bactericidal
      concentrations. The concentration-time curves of piperacillin, cefoperazone,
      meropenem and metronidazole conformed to one-compartment model, and ceftriaxone
      and levofloxacin are conformed to two-compartment model. Piperacillin/tazobactam
      and cefoperazone/sulbactam have the largest bactericidal index and the longest
      T(>MIC), so they can be chosen as the first choice for the therapy of
      hepatobiliary infection.For the anaerobic, the microbicidal potential of
      metronidazole is high.

PMID- 25573218
TI  - [Comparison of three dimensional and two dimentional laparoscopic pyeloplasty for
      ureteropelvic junction obstruction].
AB  - OBJECTIVE: To compare clinical outcomes of three dimensional (3D) and traditional
      two dimentional (2D) laparoscopic pyeloplasty for ureteropelvic junction
      obstruction (UPJO). METHODS: Clinical data on 31 patients who underwent
      retroperitoneoscopic pyeloplasty for UPJO in Peking Union Medical Hospital from
      January 2013 to March 2014 were retrospectively analyzed. There were 16 male and
      15 female patients, and the age ranged from 21 to 42 years, mean (30 +/- 6)
      years. The lesions of 20 cases were located on the left side and 11 cases on the
      right side. All cases were diagnosed as UPJO by B ultrasound and computed
      tomography urography (CTU). According to 3D or 2D laparoscopy, these patients
      were divided into two groups. The 3D laparoscopy group included 16 cases, who
      received 3D retroperitoneoscopic pyeloplasty. The 2D laparoscopy group included
      15 cases, who received traditional 2D retroperitoneoscopic pyeloplasty.
      Demographic data (gender, age, laterality, body mass index), perioperative
      indexes and clinical outcomes (operative time, estimated blood loss ,
      postoperative hospital stay, total hospitalization charge) were collected and
      compared between two groups.Numerical demographic and perioperative data were
      analyzed by using Student's t-test. Categorical data were compared using
      Pearson's Chi-square test. RESULTS: All operations were completed successfully
      without open convertion.In the 3D laparoscopy group operative time was
      significantly shorter than 2D laparoscopy group ((106 +/- 16) minutes vs. (124 +/
      24) minutes, t = 5.993, P = 0.021) . There were no significant difference
      between two groups on the estimated blood loss ((54 +/- 14) ml vs. (57 +/- 16)
      ml, t = 0.285, P = 0.598), postoperative hospital stay ((7.3 +/- 0.7) days vs.
      (7.5 +/- 0.6) days, t = 1.415, P = 0.244), incidence of postoperative
      complications (0/16 vs. 1/15, chi(2) = 1.102, P = 0.484) and total
      hospitalization charge ((25 687 +/- 3 032) RMB vs. (25 426 +/- 2 626) RMB, t =
      0.065, P = 0.800) . All patients were followed up from 3 to 12 months (mean 6
      months).Ureteropelvic junction stricture recurred in 2 cases respectively from 3D
      laparoscopic group and traditional laparoscopic group. Both were cured.
      CONCLUSIONS: 3D laparoscopic pyeloplasty is safe and feasible. Compared with the
      traditional 2D laparoscopic technology, 3D laparoscopy technology reduces the
      operation difficulty and shortens the operative time.

PMID- 25573220
TI  - [Expression and clinical significance of Tspan 1 and Integrin alpha6 in human
      pancreatic ductal adenocarcinoma].
AB  - OBJECTIVE: To explore the clinicopathological significance and relationship of
      Tspan 1 and Integrin alpha6 expression in pancreatic ductal adenocarcinoma (PDAC)
      tissue and pancreatic cancer cell lines. METHODS: Immunohistochemistry was used
      to detect the expression of Tspan 1 and Integrin alpha6 in 95 paraffin-embedded
      PDAC specimens and 55 adjacent non-cancerous pancreatic tissues which were
      collected from May 2004 to January 2013.Western blot and quantitative real-time
      polymerase chain reaction (qRT-PCR) were used to detected the protein and mRNA
      expression in 16 paired fresh PDAC specimens of the pancreas and adjacent non
      cancerous pancreatic tissues and 6 different pancreatic cancer cell lines.chi(2)
      test, Spearman-rank correlation analysis, Kaplan-Meier method and multivariate
      Cox regression analysis were used to analyze the data. RESULTS: Tspan 1 and
      Integrin alpha6 were significantly over-expressed in PDAC than in adjacent non
      cancerous pancreatic tissues (chi(2) = 7.429, P < 0.05; chi(2) = 15.1, P < 0.01).
      Lymph node metastasis, TNM stage and post-operation recurrence were positively
      correlated with the expression of Tspan 1 (chi(2) = 6.688, P < 0.01; chi(2) =
      13.055, P < 0.01; chi(2) = 6.116, P < 0.05) . TNM stage was positively correlated
      with the expression of Integrin alpha6 (chi(2) = 8.896, P < 0.05) . Tspan 1 was
      correlated with Integrin alpha6 (r = 0.223, P < 0.05) . The expressions of Tspan
      1 and Integrin alpha6 were negatively correlated with survival time (chi(2) =
      5.263, P < 0.05;chi(2) = 10.124, P < 0.01) . Multivariate analysis revealed that
      Tspan 1 and Integrin alpha6 expressions were independent prognostic factors in
      PDAC patients (chi(2) = 6.152, P < 0.05; chi(2) = 9.479, P < 0.01). Western blot
      (t = 2.278, P < 0.05; t = 3.153, P < 0.05) and qRT-PCR (t = 2.439, P < 0.05; t =
      3.258, P < 0.05) showed that Tspan 1 and Integrin alpha6 expressions were higher
      in PDAC tissues than in adjacent non-cancerous pancreatic. Tspan 1 and Integrin
      alpha6 were expressed in all six pancreatic cancer cell lines.In SW1990 which
      derived from metastasis PDAC, Tspan 1 and Integrin alpha6 expressions were higher
      than the cell lines from primary tumor. CONCLUSION: Tspan 1 and Integrin alpha6
      expression can up-regulate the invasion and metastasis of PDAC and may be used to
      predict the prognosis of PDAC.

PMID- 25573221
TI  - Effects of seated and standing cold water immersion on recovery from repeated
      sprinting.
AB  - This study investigated the effects of two different hydrostatic pressures
      (seated or standing) during cold water immersion at attenuating the deleterious
      effects of strenuous exercise on indices of damage and recovery. Twenty four male
      well-trained games players (age 23 +/- 3 years; body mass 81.4 +/- 8.7 kg:
      [Formula: see text]O2max 57.5 +/- 4.9 ml?kg(-1)?min(-1)) completed the
      Loughborough Intermittent Shuttle Test (LIST) and were randomly assigned to
      either a control, seated cold water immersion or a standing cold water immersion
      (14 min at 14 degrees C). Maximal isometric voluntary contraction, counter
      movement jump, creatine kinase, C-reactive protein, interleukin-6 and delayed
      onset muscle soreness (DOMS) were measured before and up to 72 h following the
      LIST. All dependent variables showed main effects for time (P < 0.05) following
      the LIST, indicating physiological stress and muscle damage following the
      exercise. There were no significant group differences between control and either
      of the cold water immersion interventions. Seated cold water immersion was
      associated with lower DOMS than standing cold water immersion (effect size =
      1.86; P = 0.001). These data suggest that increasing hydrostatic pressure by
      standing in cold water does not provide an additional recovery benefit over
      seated cold water immersion, and that both seated and standing immersions have no
      benefit in promoting recovery following intermittent sprint exercise.

PMID- 25573222
TI  - A renewed question in haemodialysis patients: should we correct low serum
      magnesium levels?

PMID- 25573224
TI  - Self-perceived health status of patients with adrenal insufficiency receiving
      glucocorticoid replacement therapy - French data from a worldwide patient survey.
AB  - An international survey was undertaken to investigate current practices in
      glucocorticoid replacement therapy and self-perceived health status of patients
      with adrenal insufficiency, using a 39-item questionnaire. Results were published
      in 2012. We analyzed data from French patients, extracted from the database.
      Participants were recruited via a patient advocacy group to respond anonymously
      to a questionnaire developed by clinical experts. Ninety-four patients
      participated (primary adrenal insufficiency 79% and secondary adrenal
      insufficiency 16%). They were treated mainly with hydrocortisone (97.5%). Dosing
      regimens were once daily (8%), twice daily (38%), thrice daily (30%) or other
      (24%). Nearly 80% of the participants considered their affection to have an
      impact on their physical activity, work, family or social life and 38% reported
      absence from work/school in the last 3 months. Fatigue in the morning or during
      the day was a problem for 57% and 69% of respondents respectively. Eighty percent
      were concerned about long-term side effects of therapy, mainly osteoporosis
      (79%), fatigue (57%) and obesity (43%). Despite obvious biases in the survey, we
      should be alerted by the high number of patients' complaints and the clear signs
      of quality of life impairment in this population, and think about strategies to
      improve their management. 

PMID- 25573223
TI  - Joint modeling of recurrent event processes and intermittently observed time
      varying binary covariate processes.
AB  - When conducting recurrent event data analysis, it is common to assume that the
      covariate processes are observed throughout the follow-up period. In most
      applications, however, the values of time-varying covariates are only observed
      periodically rather than continuously. A popular ad-hoc approach is to carry
      forward the last observed covariate value until it is measured again. This simple
      approach, however, usually leads to biased estimation. To tackle this problem, we
      propose to model the covariate effect on the risk of the recurrent events through
      jointly modeling the recurrent event process and the longitudinal measures.
      Despite its popularity, estimation of the joint model with binary longitudinal
      measurements remains a challenge, because the standard linear mixed effects model
      approach is not appropriate for binary measures. In this paper, we postulate a
      Markov model for the binary covariate process and a random-effect proportional
      intensity model for the recurrent event process. We use a Markov chain Monte
      Carlo algorithm to estimate all the unknown parameters. The performance of the
      proposed estimator is evaluated via simulations. The methodology is applied to an
      observational study designed to evaluate the effect of Group A streptococcus on
      pharyngitis among school children in India. 

PMID- 25573225
TI  - Coronary aneurysm and stent fracture following stenting of a myocardial bridge.
AB  - Myocardial bridge is the most common congenital coronary anomaly. We represent an
      extremely rare case of stent fracture combination with coronary aneurysm
      following stenting of a myocardial bridge. This 60-years-old male patient
      underwent coronary angiography in the local hospital four years ago. Coronary
      angiography revealed a myocardial bridge in the distal left anterior descending
      coronary artery (LAD). A 3.0 mm * 29 mm sirolimus eluting stent was deployed in
      the distal LAD. Three years later, repeat coronary angiography showed a large
      coronary aneurysm in the mid segment of the stent. The patient subsequently
      underwent coronary artery bypass grafting with left internal mammary artery
      (LIMA) to the distal segment of the LAD. But six months later, another coronary
      angiography showed a stent fracture in mid portion of the stent associated with a
      large coronary aneurysm, and the LIMA graft was totally occluded. A possible
      mechanism of stent fracture was long-standing and cyclic mechanical stress on the
      stent by myocardium. These forces over a period of time may lead to metal fatigue
      and eventually fracture. Based on the observation of fracture and aneurysm in
      this study, we recommend that myocardial bridge should not be treated with
      intracoronary stenting. (c) 2015 Wiley Periodicals, Inc. 

PMID- 25573226
TI  - Autopsy features in a newborn baby affected by a central congenital diaphragmatic
      hernia.
AB  - Congenital diaphragmatic hernia is a congenital malformation of the diaphragm,
      resulting in the herniation of the abdominal organs into the thoracic cavity. The
      most common types of congenital diaphragmatic hernia are Bochdalek hernia
      (postero-lateral hernia), Morgagni hernia (anterior defect), and diaphragm
      eventration (abnormal displacement of part or all of an otherwise intact
      diaphragm into the chest cavity). Congenital diaphragmatic hernia is a life
      threatening pathology in infants, and a major cause of death due to pulmonary
      hypoplasia and pulmonary hypertension. We present a fatal case of congenital
      diaphragmatic hernia in a newborn. At the autopsy, a central defect of the
      diaphragm was found, 8 * 5 cm in size, that led to a herniation of the small
      intestine, the right lobe of the liver, and the right adrenal gland into the
      thorax. An esophageal atresia was associated with the congenital diaphragmatic
      hernia. The lungs showed severe hypoplasia and atelectasia. Physicians should pay
      attention to a prenatal diagnosis of congenital diaphragmatic hernia in order to
      prevent newborn fatalities. 

PMID- 25573228
TI  - Do not resuscitate orders for patients with intracerebral hemorrhage: experience
      from a Chinese tertiary care center.
AB  - AIM: This study aimed to determine the frequency and determinant factors of do
      not resuscitate (DNR) orders in patients with intracerebral hemorrhage (ICH) at a
      university hospital in China. METHODS: Data collected from June 2010 to December
      2012 for patients with ICH were retrospectively reviewed. The characteristics and
      care of patients with and without DNR orders and those with early (<=24 h) and
      late (>24 h) DNR establishment were compared. RESULTS: Formal DNR orders were
      filed during hospitalization for 64/759 (8.4%) patients with complete medical
      records enrolled in this study. Patients with DNR orders were older on average
      (73.1 +/- 10.1 vs. 56.0 +/- 13.2 years; p < 0.001) and a larger proportion had
      pre-ICH comorbidity impacting dependency (87.5 vs. 17.0%; p < 0.001) than did
      those with no DNR order. Patients with DNR orders were in worse clinical
      condition on arrival than those without a DNR order, as judged by Glasgow Coma
      Scale scores, and more frequently had large hematoma volumes (78.1 vs. 39.7%; p <
      0.001). CONCLUSIONS: DNR orders were not used commonly for patients with ICH in
      this Chinese sample. No relationship between ICH severity and DNR decision making
      was observed.

PMID- 25573230
TI  - Italian research at a turning point: an opportunity that cannot be missed.

PMID- 25573227
TI  - Cardiovascular risk stratification in overweight or obese patients in primary
      prevention. Implications for use of statins.
AB  - BACKGROUND AND OBJECTIVES: Cardiovascular risk estimation in patients with
      overweight/obesity is not standardized. Our objectives were to stratify
      cardiovascular risk using different scores, to analyze use of statins, to report
      the prevalence of carotid atherosclerotic plaque (CAP), and to determine the
      optimal cut-off point (OCP) of scores that discriminate between subjects with or
      without CAP. MATERIAL AND METHODS: Non-diabetic patients with overweight or
      obesity in primary prevention were enrolled. The Framingham score (FS), the
      European score (ES), and the score proposed by the new American guidelines (NS)
      were calculated, and statin indication was evaluated. Prevalence of CAP was
      determined by ultrasound examination. A ROC analysis was performed. RESULTS: A
      total of 474 patients (67% with overweight and 33% obese) were enrolled into the
      study. The FS classified the largest number of subjects as low risk. PAC
      prevalence was higher in obese as compared to overweight subjects (44.8% vs.
      36.1%, P=.04). According to the FS, ES, and NS respectively, 26.7%, 39.1%, and
      39.1% of overweight subjects and 28.6%, 39.0%, and 39.0% of obese subjects had an
      absolute indication for statins. All three scores were shown to acceptably
      discriminate between subjects with and without CAP (area under the curve>0.7).
      The OCPs evaluated did not agree with the risk category values. CONCLUSIONS: Risk
      stratification and use of statins varied in the overweight/obese population
      depending on the function used. Understanding of the relationship between scores
      and presence of CAP may optimize risk estimate.

PMID- 25573229
TI  - The student's dilemma, liver edition: incorporating the sonographer's language
      into clinical anatomy education.
AB  - Anatomy students are often confused by multiple names ascribed to the same
      structure by different clinical disciplines. Increasingly, sonography is being
      incorporated into clinical anatomical education, but ultrasound textbooks often
      use names unfamiliar to the anatomist. Confusion is worsened when ultrasound
      names ascribed to the same structure actually refer to different structures.
      Consider the sonographic main lobar fissure (MLF). The sonographic MLF is a hyper
      echoic landmark used by sonographers of the right upper quadrant. Found in
      approximately 70% of people, there is little consensus on what the sonographic
      MLF is anatomically. This structure appears to be related to the main portal
      fissure (aka principal plane of the liver or principal hepatic fissure),
      initially described by anatomists and surgeons as in intrahepatic division along
      the middle hepatic vein which in essence divides the territories of the left and
      right hepatic arteries and biliary systems. By exploring the relationship between
      the main portal fissure and the sonographic MLF in cadaveric livers ex vivo, the
      data suggest the sonographic MLF is actually an extrahepatic structure that
      parallels the rim of the main portal fissure. The authors recommend that this
      structure be renamed the "sonographic cystic pedicle," which includes the cystic
      duct and ensheathing fat and blood vessels. In the context of the redefined
      underlying anatomy, the absence of the sonographic cystic pedicle due to anatomic
      variation may serve an important clinical role in predicting complications from
      difficult laparoscopic cholecystectomies and is deserving of future study.

PMID- 25573231
TI  - Establishing breastfeeding with the late preterm infant in the NICU.
AB  - OBJECTIVE: To describe challenges that late preterm infants (LPIs) face with
      breastfeeding and to provide an overview of current policy statements and
      practice guidelines that support breastfeeding for LPIs. In addition, we describe
      current breastfeeding research related to the LPI and combine this research with
      policies and practice guidelines to provide evidence-based recommendations to
      guide practice and future research in the NICU. DATA SOURCES: Cumulative Index to
      Nursing and Allied Health Literature and PubMed databases. STUDY SELECTION:
      Policies, guidelines, and research relevant to breastfeeding the LPI were
      selected if they were published between January 1, 2009 and March 1, 2014. All
      documents were published in English and related to breastfeeding management or
      breastfeeding outcomes for the LPI. DATA EXTRACTION: Information from articles,
      policies, and guidelines were chosen for their relevance to breastfeeding the
      LPI. DATA SYNTHESIS: Policy statements and practice guidelines were reviewed to
      provide an understanding of breastfeeding recommendations for the LPI.
      Additionally, recent research studies were reviewed and combined with the policy
      statements and practice guidelines to provide practice recommendations for NICU
      providers. CONCLUSIONS: LPIs require a unique set of interventions for
      breastfeeding success; though they might be perceived as small, full-term
      infants, these infants often have greater challenges with breastfeeding than
      their term counterparts. Future research should be directed at identifying and
      testing specific strategies that will best support this at-risk population.
      Findings from this article are applicable for the LPI in the NICU as well as
      other care areas such as special care and transitional nurseries.

PMID- 25573233
TI  - pH-controlled polymorphism in a layered dysprosium phosphonate and its impact on
      the magnetization relaxation.
AB  - Two polymorphic layered dysprosium phosphonates alpha-Dy(2-qpH)(SO4)(H2O)2 (alpha
      Dy) and beta-Dy(2-qpH)(SO4)(H2O)2 (beta-Dy) (2-qpH2 = 2-quinolinephosphonic acid)
      which crystallize in monoclinic P21/c and triclinic P1 space groups,
      respectively, are reported. Both exhibit field-induced slow relaxation of
      magnetization at low temperature. The energy barrier for beta-Dy is nearly three
      times that for alpha-Dy, attributed to the structural differences in the two
      phases.

PMID- 25573234
TI  - Causation of cerebral microbleeds: more work is urgently needed.

PMID- 25573232
TI  - Proteome scale comparative modeling for conserved drug and vaccine targets
      identification in Corynebacterium pseudotuberculosis.
AB  - Corynebacterium pseudotuberculosis (Cp) is a pathogenic bacterium that causes
      caseous lymphadenitis (CLA), ulcerative lymphangitis, mastitis, and edematous to
      a broad spectrum of hosts, including ruminants, thereby threatening economic and
      dairy industries worldwide. Currently there is no effective drug or vaccine
      available against Cp. To identify new targets, we adopted a novel integrative
      strategy, which began with the prediction of the modelome (tridimensional protein
      structures for the proteome of an organism, generated through comparative
      modeling) for 15 previously sequenced C. pseudotuberculosis strains. This pan
      modelomics approach identified a set of 331 conserved proteins having 95-100%
      intra-species sequence similarity. Next, we combined subtractive proteomics and
      modelomics to reveal a set of 10 Cp proteins, which may be essential for the
      bacteria. Of these, 4 proteins (tcsR, mtrA, nrdI, and ispH) were essential and
      non-host homologs (considering man, horse, cow and sheep as hosts) and satisfied
      all criteria of being putative targets. Additionally, we subjected these 4
      proteins to virtual screening of a drug-like compound library. In all cases,
      molecules predicted to form favorable interactions and which showed high
      complementarity to the target were found among the top ranking compounds. The
      remaining 6 essential proteins (adk, gapA, glyA, fumC, gnd, and aspA) have
      homologs in the host proteomes. Their active site cavities were compared to the
      respective cavities in host proteins. We propose that some of these proteins can
      be selectively targeted using structure-based drug design approaches (SBDD). Our
      results facilitate the selection of C. pseudotuberculosis putative proteins for
      developing broad-spectrum novel drugs and vaccines. A few of the targets
      identified here have been validated in other microorganisms, suggesting that our
      modelome strategy is effective and can also be applicable to other pathogens. 

PMID- 25573236
TI  - Brainstem auditory-evoked potential and migraine: is there an association?

PMID- 25573235
TI  - Platelet distribution width and mean platelet volume in idiopathic pulmonary
      arterial hypertension.
AB  - BACKGROUND: Previous studies have demonstrated that platelet activation occurs in
      patients with pulmonary arterial hypertension (PAH). Mean platelet volume (MPV)
      and platelet distribution width (PDW) are two markers of platelet activation, and
      have recently been recognised as risk predictors of cardiovascular diseases. This
      study aimed to investigate whether MPV and PDW would be useful to reflect disease
      severity and predict prognosis in idiopathic PAH (IPAH). METHODS: MPV and PDW
      levels were measured in 82 IPAH patients without antiplatelet or anticoagulant
      treatment on admission and 82 healthy controls. Concurrent collected data
      included clinical, haemodynamic and biochemical variables. All patients were
      followed-up from the date of blood testing. The endpoint was all-cause mortality.
      RESULTS: MPV and PDW were significantly higher in patients with IPAH than in age
      and sex-matched control subjects (11.4+/-0.9fl vs. 10.3+/-0.9fL and 14.3+/-2.9%
      vs. 11.9+/-1.9%, respectively; p=0.000). Pearson's correlation analysis revealed
      that MPV and PDW correlated positively with right ventricular systolic pressure,
      mean pulmonary arterial pressure and pulmonary vascular resistance. After a mean
      follow-up of 14+/-8 months, 12 patients died of right heart failure. Receiver
      operating characteristic analysis showed that MPV and PDW could not predict all
      cause mortality. Multivariate Cox regression analysis suggested that right/left
      ventricular end-diastolic diameter ratio and NT-proBNP were independent
      predictive parameters of all-cause mortality. CONCLUSIONS: Our results suggest
      that MPV and PDW were elevated in patients with IPAH. They could partly reflect
      disease severity, but did not predict prognosis.

PMID- 25573237
TI  - Lipopolysaccharides upregulate calcium concentration in mouse uterine smooth
      muscle cells through the T-type calcium channels.
AB  - Infection is a significant cause of preterm birth. Abnormal changes in
      intracellular calcium signals are the ultimate triggers of early uterine
      contractions that result in preterm birth. T-type calcium channels play an
      important role in the pathogenesis of cancer, as well as endocrine and
      cardiovascular diseases. However, there are limited studies on their role in
      uterine contractions and parturition. In the present study, mouse uterine smooth
      muscle cells were isolated and treated with lipopolysaccharides (LPS) to mimic
      the microenvironment of uterine infection in vitro to investigate the role of T
      type calcium channels in the process of infection-induced preterm birth. The
      results from quantitative polymerase chain reaction and western blot analysis
      showed that LPS significantly induced the expression of the Cav3.1 and Cav3.2
      subtypes of T-type calcium channels. Measurements of intracellular calcium
      concentration showed a significant increase in response to LPS. However, these
      effects can be reversed by T-type calcium channel blockers. Western blot analysis
      further indicated that LPS induced the activation of the nuclear factor (NF)
      kappaB signaling pathway, and endothelin-1 (ET-1) was significantly upregulated,
      whereas NF-kappaB inhibitors significantly inhibited the LPS-induced upregulation
      of Cav3.1, Cav3.2 and ET-1 expression. In addition, ET-1 directly induced Cav3.1
      and Cav3.2 expression, whereas ET-1 antagonists inhibited the LPS-induced
      upregulation of Cav3.1 and Cav3.2 expression. In conclusion, the present study
      demonstrates that infection triggers the upregulation of T-type calcium channels
      and promotes calcium influx. This process relies on the activation of the NF
      kappaB/ET-1 signaling pathway. The T-type calcium channel is expected to become
      an effective target for the prevention of infection-induced preterm birth. 

PMID- 25573238
TI  - The dermatologists' role in managing psoriatic arthritis: results of a Swiss
      Delphi exercise intended to improve collaboration with rheumatologists.
AB  - BACKGROUND: Psoriatic arthritis (PsA) substantially impacts the management of
      psoriatic disease. OBJECTIVE: This study aimed to generate an interdisciplinary
      national consensus on recommendations of how PsA should be managed. METHODS:
      Based on a systematic literature search, an interdisciplinary expert group
      identified important domains and went through 3 rounds of a Delphi exercise,
      followed by a nominal group discussion to generate specific recommendations.
      RESULTS: A strong consensus was reached on numerous central messages regarding
      the impact of PsA, screening procedures, organization of the interaction between
      dermatologists and rheumatologists, and treatment goals. CONCLUSION: These
      recommendations can serve as a template for similar initiatives in other
      countries. At the same time, they highlight the need to take into account the
      impact of the respective national health care system.

PMID- 25573240
TI  - Views on the co-evolution of the melanocortin-2 receptor, MRAPs, and the
      hypothalamus/pituitary/adrenal-interrenal axis.
AB  - A critical regulatory component of the hypothalamus/pituitary/adrenal axis (HPA)
      in mammals, reptiles and birds, and in the hypothalamus/pituitary/interrenal
      (HPI) axis of amphibians and teleosts (modern bony fishes) is the strict ligand
      selectivity of the melanocortin-2 receptor (MC2R). Tetrapod and teleost MC2R
      orthologs can only be activated by the anterior pituitary hormone, ACTH, but not
      by any of the MSH-sized ligands coded in POMC. In addition, both tetrapod and
      teleost MC2R orthologs require co-expression with the accessory protein, MRAP.
      However, the MC2R ortholog of the elephant shark, a cartilaginous fish, can be
      activated by either ACTH or the MSH-sized ligands, and the elephant shark MC2R
      ortholog does not require co-expression with an MRAP for activation. Given these
      observations, this review will provide a scenario for the co-evolution of MC2R
      and MRAP, based on the assumption that the obligate interaction between MC2R and
      MRAP evolved during the early radiation of the ancestral bony fishes. 

PMID- 25573241
TI  - Genome-wide transcriptome analysis of mRNAs and microRNAs in Dorset and Small
      Tail Han sheep to explore the regulation of fecundity.
AB  - A variety of sheep species with diverse fecundities are kept as livestock and
      make up the global agricultural economy. A mutation in the FecB gene has been
      implicated to be essential and additive for ovulation rate. To uncover potential
      regulators of fecundity, we performed a genome-wide analysis of mRNAs and miRNAs
      from Dorset sheep (Dorset), Small Tail Han sheep FecB(B)FecB(B) genotype (Han BB)
      and Small Tail Han sheep FecB(+)FecB(+) genotype (Han ++). Here we present
      detailed analyses at both the mRNA and miRNA levels to aid in the identification
      of candidate genes that might regulate fecundity. We found differentially
      expressed genes between each of the groups, which are involved in various
      cellular activities, such as metabolic cascades, catalytic function and signal
      transduction. Moreover, the miRNA profiling identified specific miRNAs unique to
      each group of sheep, which may play a role in the controlling fecundity
      differences. By exploring the miRNA-regulated gene expression network in the
      different sheep species we can create a stronger profile for regulation of
      fecundity. Furthermore, quantitative real-time PCR verified the reliability of
      the RNA-Seq data. To our knowledge, this is the first analysis of intravariety
      and intervariety in any species in this area. Taken together, this genome-wide
      analysis of mRNAs and miRNAs in sheep will aid in the ability to identify
      fecundity regulators between different sheep species. 

PMID- 25573242
TI  - How to perform a critical appraisal of diagnostic tests: 7 steps.
AB  - The critically appraised topic (CAT) is a format in evidence-based practice for
      sharing information. A CAT is a standardized way of summarizing the most current
      research evidence focused on a pertinent clinical question. Its aim is to provide
      both a critique of the most up-to-date retrieved research and an indication of
      the clinical relevance of results. A clinical question is initially generated
      following a patient encounter, which leads to and directs a literature search to
      answer the clinical question. Studies obtained from the literature search are
      assigned a level of evidence. This allows the most valid and relevant articles to
      be selected and to be critically appraised. The results are summarized, and this
      information is translated into clinically useful procedures and processes. 

PMID- 25573239
TI  - Favorable effect of the combination of vinorelbine and dihydropyrimidine
      dehydrogenase-inhibitory fluoropyrimidine in EGFR-mutated lung adenocarcinoma:
      retrospective and in vitro studies.
AB  - Although cytotoxic chemotherapy is essential in epidermal growth factor receptor
      (EGFR)-mutated non-small cell lung cancer (NSCLC), it is unclear which regimen is
      most effective. We retrospectively compared the efficacy of standard platinum
      based chemotherapy with that of combination chemotherapy using vinorelbine (VNR)
      plus dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine (DIF) in EGFR
      mutated lung adenocarcinomas, and we investigated a potential mechanism by which
      the combination chemotherapy of VNR + DIF was favorable in the treatment of EGFR
      mutated lung adenocarcinoma in vitro. In our retrospective analysis, the response
      rate and disease control rate afforded by the VNR + DIF treatment tended to be
      better than those by platinum-based chemotherapy, and the progression-free
      survival of the 24 VNR + DIF-treated patients was significantly longer than that
      of the 15 platinum-based chemotherapy patients. In EGFR-mutated PC9 cells, VNR
      induced EGFR dephosphorylation at a clinically achievable concentration. 1BR3-LR
      cells, a line of fibroblast cells transfected with a mutant EGFR construct, were
      completely resistant to gefitinib in the medium containing 10% fetal bovine serum
      (FBS), whereas the sensitivity of these cells to gefitinib was increased in 0.5%
      FBS-containing medium. Similarly, the sensitivity of 1BR3-LR cells to VNR was
      increased when they were cultured in low-serum condition. In addition, sodium
      orthovanadate (Na3VO4) inhibited the EGFR dephosphorylation induced by VNR or
      gefitinib and suppressed the cell growth inhibition by these agents in PC9 cells.
      VNR and gefitinib showed synergistic cell growth inhibition in combination with 5
      fluorouracil (5-FU) in PC9 cells. We propose that the EGFR dephosphorylation
      induced by VNR is related to cell growth inhibitory activity of VNR, and that
      this is one of the mechanisms of the synergistic effect of VNR + 5-FU in EGFR
      mutated lung cancer cells. In conclusion, the combination chemotherapy of VNR +
      DIF may be a promising treatment for NSCLC patients with EGFR mutations.

PMID- 25573244
TI  - Bone age assessment with conventional ultrasonography in healthy infants from 1
      to 24 months of age.
AB  - BACKGROUND: Radiographic bone age determination is part of the routine evaluation
      of suspected growth disorders. Simplicity and low cost are its major advantages,
      but although the effective dose of ionizing radiation is low, it should be taken
      into consideration given its cumulative effect. OBJECTIVES: To assess the
      chronological ultrasonographic emergence of the ossification centers of the hand
      and wrist. MATERIALS AND METHODS: Cross-sectional study of healthy patients ages
      1 to 24 months (n=498) from Buenos Aires, Argentina. All patients underwent
      ultrasonographic evaluation of the left hand and wrist to identify the different
      bone nuclei; a subgroup of infants had their nuclei measured (n=228). RESULTS:
      Girls showed an earlier emergence of the evaluated nuclei and a trend to a
      greater size than age-matched boys. Size-for-age relation showed linear increase.
      Carpal bones (capitate and hamate) were the first to appear, as early as from the
      first 3 months of life, an age gap not thoroughly present on the radiographic
      atlas developed by Greulich and Pyle. The distal epiphysis of the radius and the
      second metacarpophalangeal joint (index finger) followed in order of emergence.
      The proximal epiphysis of the first metacarpal bone (thumb) was the last to
      emerge and was infrequently found on boys at age 24 months. Overall, these
      findings are in accordance with the radiographic atlas. An ultrasonography atlas
      of the left hand and wrist was outlined for girls and boys. CONCLUSION:
      Conventional ultrasonography allows proper identification of the ossification
      centers of the hand and wrist and may become an innocuous follow-up tool for
      patients with growth disorders.

PMID- 25573243
TI  - CT and MRI of congenital nasal lesions in syndromic conditions.
AB  - Congenital malformations of the nose can be associated with a variety of
      syndromes, including solitary median maxillary central incisor syndrome, CHARGE
      syndrome, Bosma syndrome, median cleft face syndrome, PHACES association,
      Bartsocas-Papas syndrome, Binder syndrome, duplication of the pituitary gland
      plus syndrome and syndromic craniosynsotosis (e.g., Apert and Crouzon syndromes)
      among other craniofacial syndromes. Imaging with CT and MRI plays an important
      role in characterizing the nasal anomalies as well as the associated brain and
      cerebrovascular lesions, which can be explained by the intimate developmental
      relationship between the face and intracranial structures, as well as certain
      gene mutations. These conditions have characteristic imaging findings, which are
      reviewed in this article. 

PMID- 25573245
TI  - Probing the mechanisms and dynamics of gas phase hydrogen-deuterium exchange
      reactions of sodiated polyglycines.
AB  - The rate constants for H-D exchange reactions of sodiated polyglycines (GnNa(+),
      n = 2-8) and polyalanines (AnNa(+), n = 2, 3 and 5) with ND3 have been measured
      in the cell of an FT-ICR mass spectrometer. All peptides except G2Na(+) are found
      to undergo three exchange reactions, all of which are consecutive with no sign of
      multiple exchanges within a single collision event. This information has been
      used to construct full mechanistic scenarios with the help of detailed quantum
      chemical calculations of the possible reaction paths for H-D exchange. The first
      exchange is always located at the C terminus however with different mechanisms
      depending upon whether the peptide termini can (larger peptides) or cannot
      (smaller peptides) interact directly without strong energy penalty. The most
      favourable mechanisms for the second and third exchanges of the N terminus
      protons, are found to be different from those for the first for all peptide
      sizes. The peptide distortions that are necessary in order for some of these
      reactions to occur are made possible by the energy reservoir provided by the
      favorable interaction of the peptide ion with ND3. Their occurrence and variety
      preclude any general relationship between H-D exchange kinetics and the most
      stable ion structures. There is however a break at G7Na(+) in the kinetics trend,
      with a first exchange rate which is much smaller than for all other peptide
      sizes. This break can be directly related to a different structural type in which
      the C terminus is neither free nor close to the N terminus. 

PMID- 25573246
TI  - Endocannabinoid CB1 receptor-mediated rises in Ca(2+) and depolarization-induced
      suppression of inhibition within the laterodorsal tegmental nucleus.
AB  - Cannabinoid type 1 receptors (CB1Rs) are functionally active within the
      laterodorsal tegmental nucleus (LDT), which is critically involved in control of
      rapid eye movement sleep, cortical arousal, and motivated states. To further
      characterize the cellular consequences of activation of CB1Rs in this nucleus, we
      examined whether CB1R activation led to rises in intracellular Ca(2+) ([Ca(2+)]i)
      and whether processes shown in other regions to involve endocannabinoid (eCB)
      transmission were present in the LDT. Using a combination of Ca(2+) imaging in
      multiple cells loaded with Ca(2+) imaging dye via 'bulk-loading' or in single
      cells loaded with dye via a patch-clamp electrode, we found that WIN 55212-2 (WIN
      2), a potent CB1R agonist, induced increases in [Ca(2+)]i which were sensitive to
      AM251, a CB1R antagonist. A proportion of rises persisted in TTX and/or low
      extracellular Ca(2+) conditions. Attenuation of these increases by a reversible
      inhibitor of sarcoplasmic reticulum Ca(2+)-ATPases, suggests these rises occurred
      following release of Ca(2+) from intracellular stores. Under voltage clamp
      conditions, brief, direct depolarization of LDT neurons resulted in a decrease in
      the frequency and amplitude of AM251-sensitive, inhibitory postsynaptic currents
      (IPSCs), which was an action sensitive to presence of a Ca(2+) chelator. Finally,
      actions of DHPG, a mGlu1R agonist, on IPSC activity were examined and found to
      result in an AM251- and BAPTA-sensitive inhibition of both the frequency and
      amplitude of sIPSCs. Taken together, our data further characterize CB1R and eCB
      actions in the LDT and indicate that eCB transmission could play a role in the
      processes governed by this nucleus. 

PMID- 25573248
TI  - Leishmaniosis of companion animals in Europe: an update.
AB  - Leishmaniosis caused by Leishmania infantum is a vector-borne zoonotic disease
      endemic in southern Europe, but which is spreading northwards. Millions of dogs,
      cats and other non-conventional companion animals susceptible to L. infantum,
      living in European households, may develop a severe disease and contribute to the
      spread of leishmaniosis because of travelling or re-homing. Dogs are the main
      reservoir but other new reservoirs have recently been incriminated. Sand flies
      remain the sole proven vector and non-vectorial transmission has been reported at
      individual level and in areas where the vector is absent. Clinical disease
      affects only a proportion of infected dogs and a complex genetic background of
      immune response is responsible for this susceptibility. There is a wide range of
      serological and parasitological diagnostic tools available whose cost-effective
      use depends on a reasoned approach. Clinical response to treatment of sick dogs
      is variable. Clinical cure is often obtained but clinical recurrence can occur
      and post-therapy follow up should be maintained life-long. In Europe, vaccination
      can be combined with individual protection with pyrethroids as part of an
      integrated approach to prevention. L. infantum is the only species isolated from
      cats in Europe and xenodiagnosis substantiated that infected cats are infectious
      for sand flies. Feline infection may be frequent in endemic areas, but prevalence
      is generally lower than in dogs. When cats are tested by both serological and
      molecular techniques discordant results are often observed. Feline cases have
      been reported from endemic areas in Italy, France, Spain and Portugal, but four
      cases were also diagnosed in Switzerland in cats that had travelled to or been
      imported from Spain. Half of the cases were diagnosed in cats with impaired
      immune responses. Clinical manifestations compatible with feline leishmaniosis
      include lymph node enlargement, skin and mucocutaneous lesions, ocular lesions,
      chronic gingivostomatitis, hypergammaglobulinemia, and normocytic normochromic
      anemia. Cats have been empirically treated with some drugs used in dogs. Due to
      polymorphic clinical picture and the insidious progressive course, leishmaniosis
      can persist for a long time before dogs or cats are brought to a veterinarian and
      so diagnosis can be delayed. Exotic or new Leishmania spp. have been reported in
      humans, animals and vectors in Europe. This changing situation requires attention
      in Europe for designing epidemiological studies and control measures. 

PMID- 25573247
TI  - Core brain networks interactions and cognitive control in internet gaming
      disorder individuals in late adolescence/early adulthood.
AB  - Regardless of whether it is conceptualized as a behavioral addiction or an
      impulse-control disorder, internet gaming disorder (IGD) has been speculated to
      be associated with impaired cognitive control. Efficient cognitive behavior
      involves the coordinated activity of large-scale brain networks, however, whether
      the interactions among these networks during resting state modulated cognitive
      control behavior in IGD adolescents remain unclear. Twenty-eight IGD adolescents
      and twenty-five age-, gender-, and education-matched healthy controls
      participated in our study. Stroop color-word task was conducted to evaluate the
      cognitive control deficits in IGD adolescents. Functional connectivity and
      Granger Causal Analysis were employed to investigate the functional and effective
      connections within and between the salience, central executive, and default mode
      networks. Meanwhile, diffusion tensor imaging was used to assess the structural
      integrity of abnormal network connections. The abnormal functional connectivity
      within central executive networks and effective connectivity within salience
      network in IGD adolescents were detected. Moreover, the inefficient interactions
      between these two brain networks were observed. In addition, we identified
      reduced fractional anisotropy in salience network, right central executive
      network tracts, and between-network (the anterior cingulate cortex-right
      dorsolateral prefrontal cortex tracts) pathways in IGD individuals. Notably, we
      observed a significant correlation between the effective and structural
      connection from salience network to central executive network and the number of
      errors during incongruent condition in Stroop task in both IGD and control
      subjects. Our results suggested that impaired cognitive control in IGD
      adolescents is likely to be mediated through the abnormal interactions and
      structural connection between intrinsic large-scale brain networks. 

PMID- 25573249
TI  - Dyspareunia in the Context of Psychopathology, Personality Traits, and Coping
      Resources: Results From a Prospective Longitudinal Cohort Study From Age 30 to
      50.
AB  - Although dyspareunia has a major impact on sexual and general wellbeing, there
      are few data on the longitudinal development of its prevalence in representative
      study groups. Therefore, it was the aim of the present study to fill this gap by
      evaluating the prevalence of dyspareunia in a representative sample at age 30,
      35, 41, and 50. Additional aims were to determine the association between
      dyspareunia, psychopathological covariates, personality characteristics, and
      coping resources. Semi-structured interviews with single-item questions on sexual
      problems in general as well as dyspareunia were used to gain information on 1
      year as well as long-time prevalence rates. Psychopathological covariates were
      explored with the SCL-90-R. The Freiburger Personality Inventory (Freiburger
      Personlichkeits Inventar, FPI) assessed personality characteristics. Scales of
      sense of mastery and self-esteem were used to investigate coping resources.
      Twelve months prevalence of dyspareunia varied between 4.5 and 6.4 % with a mean
      of 5.6 % and a long-time risk of 19.3 %. No relation between age and the
      prevalence rates was found. Dyspareunia was related to psychopathological
      covariates, especially depression. With respect to personality traits as measured
      with the FPI only nervousness showed a significant association with dyspareunia,
      whereas coping resources were unrelated. As dyspareunia is experienced by about
      20 % of all women, it represents a frequent sexual problem. Therefore, assessment
      of dyspareunia should be integrated into primary care of women at any age and
      diagnostic as well as therapeutic strategies should be based on physiological and
      psychological factors.

PMID- 25573250
TI  - Tamarins: Insights into monogamous and non-monogamous single female social and
      breeding systems.
AB  - Tamarins are reported to live in small multimale-multifemale groups characterized
      by a single breeding female. Here we present information on the composition and
      genetic relatedness of individuals in 12 wild-trapped groups of Weddell's
      saddleback tamarins (Saguinus weddelli) from northern Bolivia to determine if
      groups are best described as nuclear or extended families suggesting social
      monogamy or whether groups contain several unrelated same sex adults indicative
      of social polyandry/polygyny. Mean group size was 6.25 including an average of
      2.16 adult males (range 1-4) and 2.08 adult females (1-3). No group contained
      only one adult male and one adult female and 25% of groups contained two parous
      females. We estimated the genetic relatedness among individuals using 13
      polymorphic microsatellite markers. Across the population, mean relatedness was
      low and not significantly different among adult males versus among adult females,
      suggesting that both sexes disperse from their natal groups. Adults of both sexes
      also tended to have close same-sex adult relatives within their groups;
      relatedness among adult females of the same group averaged 0.31 and among adult
      males was 0.26. This suggests that tamarins of one or both sexes sometimes delay
      dispersal and remain as adults in their natal group or that emigration of same
      sexed relatives into the same group may be common. Finally, parentage analyses
      indicated that, whereas the parents of juveniles generally were present in the
      group, this was not always the case. Based on these data, published reports of
      the presence of multiple breeding males and occasionally multiple breeding
      females in the same group, and the fact that less than 10% of groups in the wild
      contain a single adult male-adult female pair, we argue that social polyandry
      best characterizes the composition of tamarin groups and that monogamy is not a
      common mating pattern in Saguinus weddelli or other tamarin species.

PMID- 25573252
TI  - Medical expenditures associated with nonfatal occupational injuries among U.S.
      workers reporting persistent disabilities.
AB  - BACKGROUND: No prior study has investigated the medical expenditures associated
      with occupational injuries among U.S. workers with persistent disabilities,
      including those with physical disabilities or cognitive limitations. OBJECTIVE:
      Using the 2004-2011 Medical Expenditure Panel Survey (MEPS) data (Panels 9-15),
      we estimated the 2-year incidence and the expenditures associated with
      occupational injuries in U.S. workers with and without persistent disabilities.
      METHODS: Expenditures were compared by type of service and sources of payment. We
      estimated the mean medical expenditures using linear regression analysis to
      adjust for sociodemographics. The statistical analysis accounted for the sample
      survey design of MEPS and the highly skewed expenditure data. RESULTS: The 2-year
      cumulative incidence of occupational injuries was 13.6% (95% CI: 11.6%-15.6%) in
      workers with persistent disabilities and 7.1% (95% CI: 6.8%-7.4%) in workers
      without persistent disabilities. The average medical expenditure associated with
      new occupational injuries in the 2-year follow-up period was $3778 in workers
      with disabilities, $2212 in workers without disabilities after adjusting for
      sociodemographics and medical insurance coverage status (in 2011 U.S. dollars, p
      value = 0.0004). Of the total expenditures for occupational injuries, workers'
      compensation paid 54.6% in workers with disabilities and 58.9% in workers without
      disabilities. There was no significant difference in the proportion of injured
      workers with and without disabilities who reported receiving workers'
      compensation benefits (46.7% vs. 48.2%, p-value = 0.718). CONCLUSIONS: Workers
      with persistent disabilities had a significantly higher incidence of occupational
      injuries and higher medical costs compared with workers without persistent
      disabilities. Many questions with regard to occupational safety and worker's
      compensation benefits in workers with disabilities remain unexplored.

PMID- 25573251
TI  - Observational study of effects of Saroglitazar on glycaemic and lipid parameters
      on Indian patients with type 2 diabetes.
AB  - Cardiovascular risk reduction is an important issue in the management of patients
      with Type 2 diabetes mellitus. Peroxisome proliferator activated receptor (PPAR)
      agonists favourably influence glycaemic and lipid parameters in patients with
      Type 2 diabetes and a dual PPAR agonist is expected to have favourable effect on
      both parameters. In this study we have analyzed the effect of Saroglitazar, a
      novel dual PPAR alpha &gamma agonist, on glycaemic and lipid parameters in Indian
      patients with Type 2 diabetes. After a mean follow-up period of 14 weeks in 34
      patients, treatment with Saroglitazar, in a dose of 4 mg daily, resulted in
      significant improvement in both glycaemic and lipid parameters. There were
      significant mean reductions of fasting plasma glucose (36.71 mg/dl; p = 0.0007),
      post-prandial plasma glucose (66.29 mg/dl; p = 0.0005), glycosylated haemoglobin
      (1.13%; p < 0.0001), total cholesterol (48.16 mg/dl; p < 0.0001), low- density
      lipoprotein cholesterol (24.04 mg/dl; p = 0.0048), triglyceride (192.78 mg/dl; p
      = 0.0001), non-high density lipoprotein cholesterol (48.72 mg/dl; p < 0.0001) and
      the ratio of triglyceride and high density lipoprotein cholesterol (5.30; p =
      0.0006). There was no significant change in body weight, blood pressure, high
      density lipoprotein cholesterol and serum creatinine.

PMID- 25573254
TI  - Anaesthetic recovery in bovine youngstock: effect of thiopental vs ketamine as
      induction agents.

PMID- 25573253
TI  - Seasonal fluctuations of small mammal and flea communities in a Ugandan plague
      focus: evidence to implicate Arvicanthis niloticus and Crocidura spp. as key
      hosts in Yersinia pestis transmission.
AB  - BACKGROUND: The distribution of human plague risk is strongly associated with
      rainfall in the tropical plague foci of East Africa, but little is known about
      how the plague bacterium is maintained during periods between outbreaks or
      whether environmental drivers trigger these outbreaks. We collected small mammals
      and fleas over a two year period in the West Nile region of Uganda to examine how
      the ecological community varies seasonally in a region with areas of both high
      and low risk of human plague cases. METHODS: Seasonal changes in the small mammal
      and flea communities were examined along an elevation gradient to determine
      whether small mammal and flea populations exhibit differences in their response
      to seasonal fluctuations in precipitation, temperature, and crop harvests in
      areas within (above 1300 m) and outside (below 1300 m) of a model-defined plague
      focus. RESULTS: The abundance of two potential enzootic host species (Arvicanthis
      niloticus and Crocidura spp.) increased during the plague season within the
      plague focus, but did not show the same increase at lower elevations outside this
      focus. In contrast, the abundance of the domestic rat population (Rattus rattus)
      did not show significant seasonal fluctuations regardless of locality.
      Arvicanthis niloticus abundance was negatively associated with monthly
      precipitation at a six month lag and positively associated with current monthly
      temperatures, and Crocidura spp. abundance was positively associated with
      precipitation at a three month lag and negatively associated with current monthly
      temperatures. The abundance of A. niloticus and Crocidura spp. were both
      positively correlated with the harvest of millet and maize. CONCLUSIONS: The
      association between the abundance of several small mammal species and rainfall is
      consistent with previous models of the timing of human plague cases in relation
      to precipitation in the West Nile region. The seasonal increase in the abundance
      of key potential host species within the plague focus, but not outside of this
      area, suggests that changes in small mammal abundance may create favorable
      conditions for epizootic transmission of Y. pestis which ultimately may increase
      risk of human cases in this region.

PMID- 25573255
TI  - Effect of signs of oestrus, disease stressors and cow activity on pregnancy rate
      following artificial insemination.
AB  - The objective was to examine (a) how pregnancy rate on one farm (500 cows) was
      affected by signs of oestrus and disease stressors and (b) whether pregnancy rate
      could be maximised by considering cow activity. The signs of oestrus and timings
      were recorded at artificial insemination (AI), and cow activity was monitored by
      neck collars. Pregnancy rate tended to be higher in animals that displayed
      standing oestrus (35 v 26 per cent; P=0.06) but was 10 per cent lower in those
      cows with an elevated somatic cell count (SCC; >200,000 cells/ml milk) within 0-4
      or 4-8 weeks prior to AI (P=0.01 and 0.05, respectively), irrespective of the
      incidence of clinical mastitis prior to AI. Cow activity data were available for
      525 inseminations (from a total of 1299). The mean interval from increased
      activity to AI in all cows (11 hours 32 minutes; 95 per cent CI 10 hours 40
      minutes to 12 hours 24 minutes) was not different for cows that did or did not
      establish a pregnancy (P=0.90). The pregnancy rate improved to the average of
      unaffected cows if AI was delayed by about eight hours in animals with an
      elevated SCC 0-4 weeks prior to AI (P=0.025), indicating that, in cows with prior
      elevated SCC, AI could be repeated approximately eight hours later to achieve
      maximum pregnancy rates. 

PMID- 25573256
TI  - Trace determination of lead, chromium and cadmium in herbal medicines using
      ultrasound-assisted emulsification microextraction combined with graphite furnace
      atomic absorption spectrometry.
AB  - INTRODUCTION: The World Health Organization (WHO) recommends that medicinal
      plants should be checked for the presence of heavy metals. A preconcentration and
      separation technique for trace amounts of heavy metals from plant matrix is
      necessary in order to increase the sensitivity and precision of their
      determination. OBJECTIVE: Lead, chromium and cadmium contaminations in herbal
      medicines were monitored using ultrasound-assisted emulsification microextraction
      (USAEME) combined with graphite furnace atomic absorption spectrometry (GF-AAS).
      METHODS: In this work, the metal ions in the aqueous solution were complexed with
      ammonium pyrrolidine dithiocarbamate (APDC) and were extracted into 45 MUL of
      toluene that was sonically dispersed in the aqueous phase. The emulsion formed
      was centrifuged and 20 MUL of separated toluene was injected into a GF-AAS for
      analysis. Several factors including the kind of extraction solvent and its
      volume, sample pH, ionic strength and concentration of APDC were optimised.
      RESULTS: The linear dynamic range (LDR) values were in the range of 0.05 to 20
      ug/L and the limit of detection values were in the range of 0.002-0.03 ug/L for
      target heavy metals. Enrichment factors were obtained in the range of 70-500. The
      precision of the proposed method was <= 8% (n = 5). The obtained amounts of Pb,
      Cr and Cd in selected herbal medicines were in the standard range, according to
      the WHO reports. CONCLUSION: The USAEME with GF-AAS procedure was shown to be an
      efficient, rapid, inexpensive and eco-friendly method for the determination of
      lead, chromium and cadmium in herbal medicines. Application of the USAEME method
      leads to an increased extraction efficiency with satisfactory precision in a
      short time using an extraction solvent volume at the microlitre level.

PMID- 25573257
TI  - Association of dietary iron restriction with left ventricular remodeling after
      myocardial infarction in mice.
AB  - Several epidemiologic studies have reported that body iron status and dietary
      iron intake are related to an increased risk of acute myocardial infarction (MI).
      However, it is completely unknown whether dietary iron reduction impacts the
      development of left ventricular (LV) remodeling after MI. Here, we investigate
      the effect of dietary iron restriction on the development of LV remodeling after
      MI in an experimental model. MI was induced in C57BL/6 J mice (9-11 weeks of age)
      by the permanent ligation of the left anterior descending coronary artery (LAD).
      At 2 weeks after LAD ligation, mice were randomly divided into two groups and
      were given a normal diet or an iron-restricted diet for 4 weeks. Sham operation
      without LAD ligation was also performed as controls. MI mice exhibited increased
      LV dilatation and impaired LV systolic function that was associated with
      cardiomyocyte hypertrophy and interstitial fibrosis in the remote area, as
      compared with the controls at 6 weeks after MI. In contrast, dietary iron
      restriction attenuated LV dilatation and impaired LV systolic function coupled to
      cardiomyocyte hypertrophy and interstitial fibrosis in the remote area.
      Importantly, cardiac expression of cellular iron transport proteins, transferrin
      receptor 1 and divalent metal transporter 1 was increased in the remote area of
      MI mice compared with the controls. Dietary iron restriction attenuated the
      development of LV remodeling after MI in mice. Cellular iron transport might play
      a role in the pathophysiological mechanism of LV remodeling after MI.

PMID- 25573258
TI  - Immediate outcome after sutureless versus transcatheter aortic valve replacement.
AB  - The aim of this study was to compare the immediate outcome of patients undergoing
      transcatheter (TAVI) versus surgical aortic valve replacement with the sutureless
      Perceval bioprosthesis (SU-AVR). This is a retrospective multicenter analysis of
      773 patients who underwent either TAVI (394 patients, mean age, 80.8 +/- 5.5
      years, mean EuroSCORE II 5.6 +/- 4.9 %) or SU-AVR (379 patients, 77.4 +/- 5.4
      years, mean EuroSCORE II 4.0 +/- 3.9 %) with or without concomitant myocardial
      revascularization. Data on SU-AVRs were provided by six European institutions
      (Belgium, Finland, Germany, Italy and Sweden) and data on TAVIs were provided by
      a single institution (Catania, Italy). In-hospital mortality was 2.6 % after SU
      AVR and 5.3 % after TAVI (p = 0.057). TAVI was associated with a significantly
      high rate of mild (44.0 vs. 2.1 %) and moderate-severe paravalvular regurgitation
      (14.1 vs. 0.3 %, p < 0.0001) as well as the need for permanent pacemaker
      implantation (17.3 vs. 9.8 %, p = 0.003) compared with SU-AVR. The analysis of
      patients within the 25th and 75th percentiles interval of EuroSCORE II, i.e., 2.1
      5.8 %, confirmed the findings of the overall series. One-to-one propensity score
      matched analysis resulted in 144 pairs with similar baseline characteristics and
      operative risk. Among these matched pairs, in-hospital mortality (6.9 vs. 1.4 %,
      p = 0.035) was significantly higher after TAVI. SU-AVR with the Perceval
      prosthesis in intermediate-risk patients is associated with excellent immediate
      survival and is a valid alternative to TAVI in these patients.

PMID- 25573259
TI  - Long-term effect of beta-blocker in ST-segment elevation myocardial infarction in
      patients with preserved left ventricular systolic function: a propensity
      analysis.
AB  - The current guidelines for acute myocardial infarction (AMI) recommended that
      beta-blocker should be used in patients with decreased left ventricular (LV)
      systolic function for long-term period. However, the effect of beta-blocker in
      AMI patients with preserved LV systolic function is uncertain. We sought to
      assess the long-term effect of beta-blocker in AMI patients with preserved LV
      systolic function. During the follow-up period (1997-2011), total 3508 patients
      were performed percutaneous coronary intervention (PCI). Of these patients, 424
      AMI patients with preserved LV systolic function [ejection fraction (EF) > 40 %]
      were analyzed. Median follow-up period was 4.7 years. Then, patients were divided
      into two groups (beta-blocker group 197 patients and no-beta-blocker group 227
      patients). However, there are substantial differences in baseline characteristics
      between two groups. Therefore, we calculated propensity score to match the
      patients in beta-blocker and no-beta-blocker groups. After post-match patients (N
      = 206, 103 matched pair), beta-blocker therapy significantly reduced cardiac
      death compared with no-beta-blocker [hazard ratio (HR) 0.40, p = 0.04], whereas
      beta-blocker therapy was not associated with major adverse cardiac events (MACE)
      and all-cause death. beta-Blocker is an effective treatment for AMI patients who
      underwent PCI with preserved LV systolic function.

PMID- 25573260
TI  - Layer-specific dyssynchrony and its relationship to the change of left
      ventricular function in hypertensive patients.
AB  - Left ventricular (LV) remodeling in systemic arterial hypertension causes
      electrical conduction delay and impairs synchronous contraction, which may
      contribute to the development of heart failure. This study aimed to assess the
      change of LV mechanics in hypertension by layer-specific dyssynchrony. One
      hundred and twenty-one patients with primary hypertension and LV ejection
      fraction >50 % (mean age, 62 +/- 10 years) and 31 normotensive controls (mean
      age, 63 +/- 9 years) were prospectively included. Layer-specific dyssynchrony
      index (DI) was defined as standard deviation of time interval (TI) from the onset
      of Q wave to peak longitudinal strain obtained from 18 segments in each
      endocardial, myocardial, and epicardial layer. The global TI between the onset of
      Q wave to peak global longitudinal strain in each layer was obtained and the time
      difference (TD) of global TI between layers was calculated. DIs were
      significantly different in three layers (P < 0.001 in both groups), and were
      significantly greater in hypertensive patients than in controls except epicardial
      DI. End diastolic filling pressure and LV global longitudinal strain were related
      with endocardial DI. TD between endocardium and myocardium was greater in
      hypertensive patients than in controls (P = 0.001). Layer-specific DI revealed
      delayed contraction in each layer and between layers in hypertensive patients,
      which were apparent in endocardium and between endocardium and myocardium.
      Increased layer-specific DIs were associated with subclinical LV dysfunction,
      although LV ejection fraction was preserved. These may be helpful to understand
      layer-specific mechanical property of LV myocardium and for early detection of
      subclinical impairment of myocardial function.

PMID- 25573262
TI  - Does regular standing improve bowel function in people with spinal cord injury?

PMID- 25573263
TI  - JJ Wyndaele ISCOS President.

PMID- 25573261
TI  - Global ITC fitting methods in studies of protein allostery.
AB  - Allostery is a nearly ubiquitous feature of biological systems in which ligand
      binding or covalent modification at one site alters the activities of distant
      sites in a macromolecule or macromolecular complex. The molecular mechanisms
      underlying this phenomenon have been studied for decades. Nevertheless there are
      many aspects that remain poorly understood. ITC yields detailed information on
      the thermodynamics of biomacromolecular interactions and their coupling to
      additional equilibria, therefore in principle it is a powerful tool for better
      understanding how allostery is achieved. A particularly powerful approach
      involves simultaneously fitting multiple ITC data sets together with those of
      complementary techniques, especially nuclear magnetic resonance and circular
      dichroism spectroscopies. In this review, we describe several group-fitting
      methods for discriminating between different binding models and for improving the
      accuracy of thermodynamic parameters extracted from variable-temperature ITC
      data. The techniques were applied to the antibiotic resistance-causing enzyme
      aminoglycoside-6'-acetyltransferase Ii, uncovering the existence of competition
      between opposing mechanisms and ligand-dependent switching of the underlying
      mechanism. These novel observations underline the potential of combining ITC and
      spectroscopic techniques to study allostery. 

PMID- 25573265
TI  - Fatal hyperammonemia after repeat renal transplantation.
AB  - A 35-year-old man had symptomatic hyperammonemia and normal liver function after
      repeat kidney transplantation. He presented with gastrointestinal symptoms, which
      quickly progressed to altered mental status. Therapy was instituted to clear the
      ammonia, but the ammonia level continued to rise. Eventually, the patient became
      unresponsive, and an emergent computed tomographic scan showed cerebral
      herniation. Urine acids and serum organic acids were not diagnostic of any urea
      cycle disorder. Histology did not reveal a clear etiology for the hyperammonemia.

PMID- 25573264
TI  - Activation of Nfatc2 in osteoblasts causes osteopenia.
AB  - Nuclear factor of activated T-cells (Nfat) c1 to c4 are transcription factors
      that play an undisputable role in osteoclastogenesis. However, Nfat function in
      osteoblastic cells is controversial. Constitutive activation of Nfatc1 and c2 in
      osteoblasts suppresses cell function, although the study of Nfat in vivo has
      yielded conflicting results. To establish the consequences of Nfatc2 activation
      in osteoblasts, we generated transgenic mice where a 3.6 kb fragment of the
      collagen type I alpha1 promoter directs expression of a constitutively active
      Nfatc2 mutant (Col3.6-Nfatc2). The skeletal phenotype of Col3.6-Nfatc2 mice of
      both sexes and of sex-matched littermate controls was investigated by
      microcomputed tomography and histomorphometry. Col3.6- Nfatc2 mice were born at
      the expected Mendelian ratio and appeared normal. Nfatc2 expression was confirmed
      in parietal bones from 1 and 3 month old transgenic mice. One month old Col3.6
      Nfatc2 female mice exhibited cancellous bone compartment osteopenia secondary to
      a 30% reduction in bone formation. In contrast, cancellous femoral bone volume
      and bone formation were not altered in male transgenics, whereas osteoblast
      number was higher, suggesting incomplete osteoblast maturation. Indices of bone
      resorption were not affected in either sex. At 3 months of age, the skeletal
      phenotype evolved; and Col3.6-Nfatc2 male mice exhibited vertebral osteopenia,
      whereas femoral cancellous bone was not affected in either sex. Nfatc2 activation
      in osteoblasts had no impact on cortical bone structure. Nfatc2 activation
      inhibited alkaline phosphatase activity and mineralized nodule formation in bone
      marrow stromal cell cultures. In conclusion, Nfatc2 activation in osteoblasts
      inhibits bone formation and causes cancellous bone osteopenia.

PMID- 25573266
TI  - Using linked birth, notification, hospital and mortality data to examine false
      positive meningococcal disease reporting and adjust disease incidence estimates
      for children in New South Wales, Australia.
AB  - Meningococcal disease is a rare, rapidly progressing condition which may be
      difficult to diagnose, disproportionally affects children, and has high morbidity
      and mortality. Accurate incidence estimates are needed to monitor the
      effectiveness of vaccination and treatment. We used linked notification,
      hospital, mortality and birth data for all children of an Australian state (2000
      2007) to estimate the incidence of meningococcal disease. A total of 595 cases
      were notified, 684 cases had a hospital diagnosis, and 26 cases died from
      meningococcal disease. All deaths were notified, but only 68% (466/684) of
      hospitalized cases. Of non-notified hospitalized cases with more than one
      clinical admission, most (90%, 103/114) did not have meningococcal disease
      recorded as their final diagnosis, consistent with initial 'false-positive'
      hospital meningococcal disease diagnosis. After adjusting for false-positive
      rates in hospital data, capture-recapture estimation suggested that up to four
      cases of meningococcal disease may not have been captured in either notification
      or hospital records. The estimated incidence of meningococcal disease in NSW-born
      and -resident children aged 0-14 years was 5.1-5.4 cases/100 000 child-years at
      risk, comparable to international estimates using similar methods, but lower than
      estimates based on hospital data. 

PMID- 25573267
TI  - Picosecond dynamics of photoexcited DNO-bound myoglobin probed by femtosecond
      vibrational spectroscopy.
AB  - Like nitric oxide (NO), nitroxyl (HNO), a reduced form of NO, plays many
      biologically important roles including neurological function and vascular
      regulation. Although HNO is unstable in aqueous solution, it is exceptionally
      stable on binding to ferrous myoglobin (Mb) to form MbHNO. Various experimental
      and theoretical investigations has been carried out to unveil the structure of
      the active site and binding characteristics of MbHNO that can explain its
      functioning mechanism and the origin of its unusual stability. However, the
      binding dynamics of HNO to Mb, as well as the photochemical and photophysical
      processes associated with binding, have not been fully established. Herein,
      femtosecond vibrational spectroscopy was used to probe the photoexcitation
      dynamics of excited MbDNO in D2O solution at 294 K with a 575 nm pulse. Time
      resolved spectra were described by three vibrational bands near 1380 cm(-1), in
      the expected N-O stretching (nuN-O) mode of MbDNO, and all three bands showed
      instantaneous bleach that decays on a picosecond time scale. The three bands were
      assigned based on isotope shifts upon (15)N substitution and ab initio
      calculation of the vibrational frequency on a DNO-bound model heme. These three
      bands likely arise from Fermi interactions between the strong nuN-O mode and the
      weak overtone and combination modes of the N atom-related modes. The immediate
      appearance of the bleach in these bands and the picosecond decay of the bleach
      indicate that most of the photoexcited MbDNO undergoes picosecond geminate
      rebinding (GR) of DNO to Mb subsequent to its immediate deligation. Ultrafast and
      efficient GR of DNO likely arises from the bonding structure of the ligand and
      high reactivity between DNO and Mb. 

PMID- 25573268
TI  - Radium-223 dichloride: a novel treatment option for castration-resistant prostate
      cancer patients with symptomatic bone metastases.
AB  - OBJECTIVE: To review and evaluate the clinical trial efficacy and safety of
      radium 223 ((223)Ra) along with its place in therapy in men with castration
      resistant prostate cancer (CRPC). DATA SOURCES: A literature search in
      PubMed/MEDLINE (up to October 2014) was performed using various combinations of
      the terms radium, hormone-refractory prostate cancer, and castration-resistant
      prostate cancer. The New Drug Application Medical, Pharmacology, and Clinical
      Pharmacology and Biopharmaceutics Reviews for radium (223)Ra dichloride were also
      utilized. The bibliographies of articles were reviewed to identify additional
      references. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2, and 3 studies that
      assessed the safety and/or efficacy of (223)Ra in patients with CRPC were
      reviewed. Peer-reviewed articles with clinically relevant information were
      reviewed for background information. DATA SYNTHESIS: In May 2013, the Food and
      Drug Administration approved intravenous use of (223)Ra for the treatment of
      patients with CRPC, symptomatic bone metastases, and no known visceral metastatic
      disease. In a phase 3 study comparing (223)Ra and the best standard of care (SOC)
      versus the best SOC plus placebo, (223)Ra was shown to increase survival. The
      most commonly seen adverse drug reactions and hematological laboratory
      abnormalities with (223)Ra include nausea, diarrhea, vomiting, peripheral edema,
      anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.
      CONCLUSIONS: (223)Ra is a first-in-class alpha-particle-emitting radioactive
      agent that is first-line therapy, providing an extra option for men suffering
      from CRPC with symptomatic bone metastases and no known visceral metastases.
      (223)Ra has also been shown to be relatively well tolerated when up to 6
      injections are given. Further studies are needed to evaluate whether (223)Ra is
      safe and effective for more than 6 doses and if it can be used concomitantly with
      chemotherapy.

PMID- 25573270
TI  - Sweetness and light: design and applications of photo-responsive glycoconjugates.
AB  - Carbohydrate-protein binding is a supramolecular recognition process that
      underpins myriad biological events. However, the precise conformational and
      configurational requirements for biomolecular recognition are often poorly
      understood, since such phenomena often occur in a strongly spatiotemporal manner.
      Photoswitchable glycoconjugates have emerged as promising investigational tools
      for probing carbohydrate-protein recognition and for controlling bacterial
      adhesion. Reversible photoisomerisation, in particular that of azobenzene
      glycoconjugates, has also been exploited as a promising strategy for controlling
      supramolecular self-assembly and macroscopic properties, thereby facilitating the
      development of light responsive carbohydrate-based materials. The following
      review will highlight the recent advances in the design and applications of
      photoswitchable glycoconjugates, paying particular attention to the application
      of light as a stimulus for modulating protein and cellular adhesion,
      amphiphilicity and supramolecular assembly of carbohydrate-based materials. 

PMID- 25573269
TI  - Staphylococcus aureus infections among children receiving a solid organ
      transplant: clinical features, epidemiology, and antimicrobial susceptibility.
AB  - BACKGROUND: Staphylococcus aureus is among the most common causes of healthcare
      associated infection (HAI) in the United States. Patients who have received a
      solid organ transplant (SOT) represent a unique population for the acquisition of
      HAIs, given their preoperative organ failure, immunosuppression, and need for
      invasive procedures. However, limited literature is published on S. aureus
      infections among children with SOT. We describe the epidemiology, antimicrobial
      susceptibility, and clinical features of S. aureus infections among pediatric SOT
      recipients. DESIGN: An ongoing prospective S. aureus surveillance database from
      2001 to 2012 was searched for infections in patients with a history of SOT at
      Texas Children's Hospital. Medical records and antibiotic susceptibility profiles
      were reviewed; specific attention was applied to the time since transplantation
      to infection. RESULTS: Out of the total of 696 transplants performed during the
      study period, 38 pediatric SOT recipients developed 41 S. aureus infections; the
      highest incidence of infection was among heart recipients. Overall, the most
      common infectious diagnoses were skin-and-soft-tissue infections (66.1%),
      followed by bacteremia (15.3%). Among isolates in SOT patients, 47.5%, 16.9%, and
      6.7% were resistant to methicillin, clindamycin, or mupirocin, respectively.
      Three infections (7.3%) occurred in the early post-transplant period (<1 month),
      all of which were bacteremia (P = 0.007) and all caused by methicillin
      susceptible S. aureus (MSSA). The majority of infections (90.2%) occurred in the
      late post-transplant period (>6 months). In 10 cases (16.9%), S. aureus infection
      was associated with graft rejection during the same admission. CONCLUSIONS: S.
      aureus represents an important cause of morbidity in pediatric SOT recipients.
      While the majority of infections occurred late after transplant (>6 months),
      those acquired in the early post-transplant period were more often invasive and
      caused by MSSA in our hospital. Physicians caring for SOT recipients should be
      aware of the risks posed by this pathogen and the potential concomitant morbidity
      including graft rejection.

PMID- 25573271
TI  - Chemical constituents from Piper wallichii.
AB  - Fifteen known compounds including four triterpenoids (1-4), one sterol (5), one
      diketopiperazine alkaloid (6) and nine phenolics (7-15) were isolated from the
      stems of Piper wallichii. Their structures were elucidated by means of
      spectroscopic analysis, and acidic hydrolysis in case of the 2-oxo
      3beta,19alpha,23-trihydroxyurs-12-en-28-oic acid beta-D-glucopyranosyl ester (1).
      The structure of compound 1 was fully assigned by 1D and 2D NMR experiments for
      the first time. All isolates were tested for their antibacterial, antifungal,
      anti-inflammatory and antiplatelet aggregation bioactivities. 

PMID- 25573272
TI  - Effect of a nutritional supplement on hair loss in women.
AB  - BACKGROUND: Female pattern hair loss is a frequent and distressing condition.
      AIM: To evaluate vs. control, the effects on hair loss of a 6-month
      supplementation with specific omega 3&6 and antioxidants. METHODS: One hundred
      and twenty healthy female subjects participated in this 6-month, randomized,
      comparative study. The primary endpoint was the change in hair density evaluated
      on standardized photographs. Secondary endpoints included changes in telogen hair
      percentage and diameter distribution of anagen hair (>40 um vs. <=40 um) measured
      by trichogram. Overall changes in hair density and diameter were also measured by
      trichometer and by subjects' self-assessment. RESULTS: After 6 months of
      treatment, photograph assessment demonstrated a superior improvement in the
      supplemented group (P < 0.001). The telogen hair percentage was significantly (P
      < 0.001) reduced in the supplemented group. The proportion of nonvellus anagen
      hair (>40 um) increased compared to the control group. The trichometer index
      increased in the supplemented group, while it decreased in the control group. A
      large majority of supplemented subjects reported a reduction in hair loss (89.9%
      of subjects at 6 months), as well as an improvement in hair diameter (86.1%) and
      hair density (87.3%). CONCLUSION: A 6-month supplementation with omega 3&6 and
      antioxidants acts efficiently against hair loss in improving hair density and
      reducing the telogen percentage and the proportion of miniaturized anagen hair.
      Objectively measured improvements were confirmed by the subjects' perception of
      efficacy.

PMID- 25573273
TI  - Comparative exomics of Phalaris cultivars under salt stress.
AB  - BACKGROUND: Reed canary grass (Phalaris arundinacea) is an economically important
      forage and bioenergy grass of the temperate regions of the world. Despite its
      economic importance, it is lacking in public genomic data. We explore comparative
      exomics of the grass cultivars in the context of response to salt exposure. The
      limited data set poses challenges to the computational pipeline. METHODS: As a
      prerequisite for the comparative study, we generate the Phalaris reference
      transcriptome sequence, one of the first steps in addressing the issue of paucity
      of processed genomic data in this species. In addition, the differential
      expression (DE) and active-but-stable genes for salt stress conditions were
      analyzed by a novel method that was experimentally verified on human RNA-seq
      data. For the comparative exomics, we focus on the DE and stable genic regions,
      with respect to salt stress, of the genome. RESULTS AND CONCLUSIONS: In our
      comparative study, we find that phylogeny of the DE and stable genic regions of
      the Phalaris cultivars are distinct. At the same time we find the phylogeny of
      the entire expressed reference transcriptome matches the phylogeny of only the
      stable genes. Thus the behavior of the different cultivars is distinguished by
      the salt stress response. This is also reflected in the genomic distinctions in
      the DE genic regions. These observations have important implications in the
      choice of cultivars, and their breeding, for bio-energy fuels. Further, we
      identified genes that are representative of DE under salt stress and could
      provide vital clues in our understanding of the stress handling mechanisms in
      general.

PMID- 25573274
TI  - Characterization of the dengue outbreak in Nuevo Leon state, Mexico, 2010.
AB  - We studied serotypes circulating dengue virus (DENV) cases, entomological Breteau
      index, rain-fall index and epidemiology of groups affected during the 2010
      outbreak in Nuevo Leon, Mexico. From 2,271 positive cases, 94% were dengue
      classic and 6% dengue hemorrhagic fever; DENV1 was mainly isolated (99%) (Central
      American lineage of American-African-genotype). We found correlation between two
      environmental phenomena (Increment of rainfall and vector-indexes) (p <= 0.05)
      with epidemiological, clinical and risk of DENV-1 ongoing transmission.

PMID- 25573275
TI  - Algal lectin binding to core (alpha1-6) fucosylated N-glycans: structural basis
      for specificity and production of recombinant protein.
AB  - We determined the specificity of BTL, a lectin from the red marine alga
      Bryothamnion triquetrum, toward fucosylated oligosaccharides. BTL showed a strict
      specificity for the core alpha1,6-fucosylation, which is an important marker for
      cancerogenesis and quality control of therapeutical antibodies. The double
      fucosylation alpha1,6 and alpha1,3 was also recognized, but the binding was
      totally abolished in the sole presence of the alpha1,3-fucosylation. A more
      detailed analysis of the specificity of BTL showed a preference for bi- and tri
      antennary nonbisected N-glycans. Sialylation or fucosylation at the nonreducing
      end of N-glycans did not affect the recognition by the lectin. BTL displayed a
      strong affinity for a core alpha1,6-fucosylated octasaccharide with a Kd of 12
      MUM by titration microcalorimetry. The structural characterization of the
      interaction between BTL and the octasaccharide was obtained by STD-NMR. It
      demonstrated an extended epitope for recognition that includes the fucose
      residue, the distal GlcNAc and one mannose residue. Recombinant rBTL was obtained
      in Escherichia coli and characterized. Its binding properties for carbohydrates
      were studied using hemagglutination tests and glycan array analysis. rBTL was
      able to agglutinate rabbit erythrocytes with strong hemagglutination activity
      only after treatment with papain and trypsin, indicating that its ligands were
      not directly accessible at the cell surface. The hemagglutinating properties of
      rBTL confirm the correct folding and functional state of the protein. The results
      show BTL as a potent candidate for cancer diagnosis and as a reagent for the
      preparation and quality control of antibodies lacking core alpha1,6-fucosylated N
      glycans. 

PMID- 25573278
TI  - Heavy metal contamination in street dusts with various land uses in Zahedan,
      Iran.
AB  - A total of 78 street dust samples (75 within city and 3 from suburban) were
      collected from different areas with various land use within the city of Zahedan
      in November 2013 at the end of a long dry period. After digestion, the
      concentrations of Cd, Cr, Cu, Ni, Pb, and Zn were measured by using ICP-OES. The
      degree of pollution by heavy metals was assessed with respect to the background
      concentration by calculation and comparison of the pollution index, integrated
      pollution index (IPI) and enrichment factor (EF). The mean IPI values (aggregate
      of six heavy metals) in commercial, high traffic, industrial, urban park, and
      residential were 3.65, 2.76, 1.68, 1.53 and 1.25, respectively. The results of EF
      analysis showed almost all sampled urban land use types to be enriched in heavy
      metals compared with sampled background levels, suggesting heavy metals
      contamination of street dust in the urban center is from anthropogenic sources.

PMID- 25573277
TI  - ZGDHu-1 induces G2/M phase arrest and apoptosis in Kasumi-1 cells.
AB  - The present study examined the effects of N,N'-di-(m-methylphenyi)-3, 6-dimethyl
      1, 4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1), a novel oxazine
      derivative, in Kasumi-1 cells. Following incubation with various concentrations
      of ZGDHu-1, fluorescence-activated cell sorting (FACS) was used in order to
      detect changes in mitochondrial membrane permeability in Kasumi-1 cells. Western
      blot analysis was performed in order to analyze the expression of nuclear factor
      kappaB, inhibitor of kappaB and AML1/ETO. In addition FACS was used to analyze
      leukemia cell cycles and the expression levels of cyclin, cyclin-dependent
      kinases and cyclin-dependent kinase inhibitors in G2/M phase were determined
      using FACS and western blot analysis. The upregulation of reactive oxygen species
      production and mitochondrial membrane permeability was ascribed to apoptosis. The
      growth of Kasumi-1 cells was inhibited through the downregulation of nuclear
      factor-kappaB, degradation of AML1/ETO fusion protein and cell cycle arrest at
      the G2/M phase. This study documented that G2/M regulatory molecules, including
      cyclin B1, cell division control (cdc)2 and cdc25c were downregulated and
      checkpoint kinase 1 (CHK1), p53, p27, phospho-cdc25c, phospho-CHK1 and phospho
      p53 were upregulated following treatment with ZGDHu-1. In the present study,
      pretreatment with CHIR-124, a selective CHK1 inhibitor, abrogated G2/M arrest via
      ZGDHu-1. These results demonstrated the anti-tumor activity of ZGDHu-1, which may
      therefore a potential target for further investigation and may be useful for the
      treatment of patients with t(8;21) acute myeloid leukemia.

PMID- 25573279
TI  - Nickel and Copper Toxicity to Embryos of the Long-Spined Sea Urchin, Diadema
      savignyi.
AB  - The sensitivity of long-spined sea urchins (Diadema savignyi) collected from Guam
      (Northern Marianas Islands), USA, to nickel and copper in seawater was explored
      using 48-h embryo-larval development toxicity tests. The median effective
      concentrations (EC50) averaged 94 ug L(-1) for nickel, and 19 ug L(-1) from a
      single exposure to copper, and suggest relatively high sensitivity of this
      species to nickel compared with other sea urchin genera, but similar sensitivity
      to copper. Ambient nickel and copper concentrations concurrently sampled from 16
      near-shore locations around Guam were one to two orders of magnitude lower than
      those that would be expected to result in adverse effects to D. savignyi embryos.
      Although nationally recommended chronic ambient water quality criteria, currently
      8.2 and 3.1 ug L(-1) for nickel and copper, respectively, were not exceeded,
      recently derived qualifying toxicity data should be considered for updating these
      criteria to ensure protectiveness of sensitive tropical species.

PMID- 25573280
TI  - Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor
      development by suppressing cell proliferation.
AB  - Garlic and its constituents are reported to have a preventive effect against
      colorectal cancer in animal models. Aged garlic extract (AGE), which is produced
      by natural extraction from fresh garlic for more than 10 months in aqueous
      ethanol, also has reputed chemopreventive effects on colon carcinogenesis, but
      has never been studied for its effects on colon cancer development. We
      investigated the antitumor effects of AGE in rats with 1,2-dimethylhydrazine
      (DMH)-induced carcinogenesis, and the mechanism of AGE in human colon cancer cell
      proliferation. F344 rats randomly divided into three groups were administered DMH
      (20 mg/kg weight) subcutaneously once a week for 8 weeks in a basal diet. After
      the last injection, one group of rats was then moved onto a basal diet containing
      3% wt/wt AGE, and rats were sacrificed at 8 or 31 weeks. The number of aberrant
      crypt foci (ACF), histological type of tumor and proliferative activity of the
      tumor lesions were analyzed by macroscopic, pathological and immunohistochemical
      methods. DLD-1 human colon cancer cells were utilized to investigate the effect
      of AGE on anti-cell proliferation. AGE decreased the number of ACF but had no
      effect on gross tumor pathology. AGE showed a lower number of adenoma and
      adenocarcinoma lesions by histological analysis. Immunohistochemical staining
      indicated that AGE suppressed the proliferative activity in adenoma and
      adenocarcinoma lesions, but showed no effect on normal colon mucosa. Moreover, we
      demonstrated that AGE delayed cell cycle progression by downregulating cyclin B1
      and cdk1 expression via inactivation of NF-kappaB in the human colorectal cancer
      cells but did not induce apoptosis. These findings suggest that AGE has an
      antitumor effect through suppression of cell proliferation.

PMID- 25573276
TI  - Identification of a fourth mannose 6-phosphate binding site in the cation
      independent mannose 6-phosphate receptor.
AB  - The 300 kDa cation-independent mannose 6-phosphate receptor (CI-MPR) plays an
      essential role in lysosome biogenesis by targeting ~ 60 different phosphomannosyl
      containing acid hydrolases to the lysosome. This type I membrane glycoprotein has
      a large extracellular region comprised of 15 homologous domains. Two mannose 6
      phosphate (M6P) binding sites have been mapped to domains 3 and 9, whereas domain
      5 binds preferentially to the phosphodiester, M6P-N-acetylglucosamine (GlcNAc). A
      structure-based sequence alignment predicts that the C-terminal domain 15
      contains three out of the four conserved residues identified as essential for
      carbohydrate recognition by domains 3, 5 and 9 of the CI-MPR, but lacks two
      cysteine residues that are predicted to form a disulfide bond. To determine
      whether domain 15 of the CI-MPR has lectin activity and to probe its carbohydrate
      binding specificity, truncated forms of the CI-MPR were tested for binding to
      acid hydrolases with defined N-glycans in surface plasmon resonance analyses, and
      used to interrogate a phosphorylated glycan microarray. The results show that a
      construct encoding domains 14-15 binds both M6P and M6P-GlcNAc with similar
      affinity (Kd = 13 and 17 MUM, respectively). Site-directed mutagenesis studies
      demonstrate the essential role of the conserved Tyr residue in domain 15 for
      phosphomannosyl binding. A structural model of domain 15 was generated that
      predicted an Arg residue to be in the binding pocket and mutagenesis studies
      confirmed its important role in carbohydrate binding. Together, these results
      show that the CI-MPR contains a fourth carbohydrate-recognition site capable of
      binding both phosphomonoesters and phosphodiesters.

PMID- 25573281
TI  - Cobalt(III)porphyrin to target G-quadruplex DNA.
AB  - G-quadruplex DNA ligands attract much attention because of their potential use in
      biology. Indeed they may interfere with G-quadrulex nucleic acid function in
      cells. Most of the G-quadruplex ligands so far reported (including also metal
      complexes) are large planar aromatic compounds that interact by pi-pi stacking
      with an external G-quartet of quadruplex. Porphyrins are well-known G-quadruplex
      ligands. We report herein a new porphyrin scaffold (meso-tetrakis(4-(N-methyl
      pyridinium-2-yl)phenyl)porphyrin) able to strongly and selectively bind to G
      quadruplex DNA. We show that even when this porphyrin is metallated with
      cobalt(III), i.e. it carries two water molecules as axial ligands on the cobalt
      ion, on each face of the porphyrin, the interaction occurs by a pi-stacking-like
      mode with an external G-quartet of quadruplex DNA.

PMID- 25573282
TI  - Limited echocardiography in the management of critically ill patients in shock.

PMID- 25573283
TI  - Effect of early mobilization on sedation practices in the neurosciences intensive
      care unit: a preimplementation and postimplementation evaluation.
AB  - INTRODUCTION: The use of sedation and analgesia protocols, daily interruption of
      sedation, and early mobilization (EM) have been shown to decrease duration of
      mechanical ventilation and hospital length of stay (LOS). METHODS: A
      retrospective chart review was conducted during a 6-month premobilization (pre
      EM) and 6-month postmobilization (post-EM) period. Patients older than 18 years
      who were admitted to the neurosciences intensive care unit (ICU) and mechanically
      ventilated for at least 24 hours without documentation of withdrawal of life
      support or brain death were included. RESULTS: Thirty-one pre-EM and 37 post-EM
      patients were included. Baseline demographics were similar with the exception of
      more ischemic stroke patients in the pre-EM group (P < .05). In the pre-EM and
      post-EM groups, patients received similar cumulative doses of propofol,
      dexmedetomidine, and benzodiazepines but higher median (interquartile range)
      doses of opioids (50.0 [13.8-165.0] vs 173.3 [41.2-463.2] MUg of fentanyl
      equivalents [P < .05]) in the post-EM group. Neurosciences ICU LOS was 10 (6-19)
      and 13 (8-18) days, respectively (P = .188). CONCLUSIONS: After implementation of
      an EM program, an increase in opioid use and no significant change in other
      sedatives were observed. Despite an increase in the amount of physical therapy
      and occupational therapy provided to patients, there was no change in hospital
      and ICU LOS or duration of mechanical ventilation.

PMID- 25573284
TI  - Comparative study between photodynamic and antibiotic therapies for treatment of
      footpad dermatitis (bumblefoot) in Magellanic penguins (Spheniscus magellanicus).
AB  - BACKGROUND: Bumblefoot, referring to bed-sore-like foot lesions, is one of the
      most important clinical complications in captive birds and has a multifactorial
      etiology. Photodynamic therapy has been proposed as an alternative treatment for
      localized infections in response to the escalating problem of antibiotic
      resistance. The aim of this study was to compare outcomes in a group of captive
      Spheniscus magellanicus with bumblefoot lesions treated with photodynamic therapy
      (PDT) or antibiotics (ATB). METHODS: Ten captive Magellanic penguins with
      preexisting stage III bumblefoot lesions were selected and randomly divided into
      one PDT and one ATB group, each including 11 pelvic-limb lesions. All animals
      underwent surgical debridement of lesions. In the ATB group, antibiotic ointment
      was applied topically three times a week, and systemic antibiotic and anti
      inflammatory drugs were administered daily. In the PDT group, photodynamic
      therapy was applied three times a week without the use of topical or systemic
      medication. Lesion areas were photographed, and swabs were collected for culture
      and sensitivity, on the first day and every 14 days for a total of 84 days. The
      four species of bacteria showing the most resistance to the antibiotics screened
      on the antibiogram were used to determine resistance to PDT with an in vitro
      test. RESULTS: There were significant differences in healing rate and average
      healing time between the PDT and ATB groups (63.62% vs. 9.09% and 42 vs. 70 days,
      respectively). CONCLUSION: The findings of this study attest to the effectiveness
      of photodynamic therapy for the treatment of stage III bumblefoot in Spheniscus
      magellanicus.

PMID- 25573285
TI  - Effects of plasma membrane ABCB6 on 5-aminolevulinic acid (ALA)-induced porphyrin
      accumulation in vitro: tumor cell response to hypoxia.
AB  - BACKGROUND: Currently, 5-aminolevulinic acid-based photodynamic diagnosis (ALA
      PDD) is used to detect tumors during surgery and exploit tumor-specific
      accumulation of protoporphyrin IX (PpIX) after administration of ALA. In a recent
      study, we showed that the human ATP-binding cassette transporter ABCG2 plays a
      key role in the regulation of PpIX as a specific exporter. However,
      coproporphyrin III (CPIII) was also detected in urine after ALA administration in
      patients with tumor, indicating the presence of a CPIII transporter. METHODS: We
      used two lines of human gastric cancer cells to measure the ALA-induced porphyrin
      metabolism. Intracellular and extracellular porphyrin levels and expressions of
      transporter were determined. RESULTS: In the present study, we showed that
      although ABCG2 did not transport CPIII, plasma membrane ABCB6 did. Moreover,
      under conditions of hypoxia, the expression of ABCB6 in plasma membrane was
      upregulated, resulting in increased extracellular CPIII concentrations.
      CONCLUSION: These data indicate that the expression of ABCB6 in plasma membrane
      is important for porphyrin accumulation after ALA administration, including
      hypoxic conditions.

PMID- 25573286
TI  - Eradication of C. albicans and T. rubrum with photoactivated indocyanine green,
      Citrus aurantifolia essential oil and fluconazole.
AB  - BACKGROUND: We aimed to evaluate the efficacy of alternative therapies rather
      than the current antifungal conventional therapy and with assessing the
      hypothesis of photoactivation of citrus essential oil, fluconazole and
      Indocyanine green to treat two common mucocutaneous fungal infections. METHODS:
      Suspensions of Candida albicans and Tricophyton rubrum containing 10(6)cells/ml
      was prepared. Equal samples were treated with infrared (IR) laser irradiation
      (810 nm, 55 J/cm(2)) in the presence of Indocyanine green (Emundo, 1 mg/ml)
      (IRLE), photoactivated Citrus aurantifolia essential oil (EO) with sequential
      exposure to natural and tungsten lights (CE), control non-activated essential oil
      (CC), laser alone (IRL), indocyanine green alone (E) and neither of treatments as
      the control group (C). Additional fluconazole (FL, 25.6 MUg/ml) and IR activated
      fluconazole (IRLFL) groups were designed for T. rubrum fungi. Inoculums were
      serially diluted to 10(-2) and 10(-4) and streaked on Sabouraud dextrose agar
      plates. Final outcomes were assessed as the percent of reduction. RESULTS: Cell
      reduction rates (%) in C. albicans groups were 99.99 (CE), 91.67 (IRLE), 86.67
      (CC), 72.37 (E) and 67.27 (RL). Whereas, a 99.99 (CE), 89.99 (CC), 74.5 (IRLE),
      64.5 (E), 38.5 (IRLF), 37.5 (RL), and 31 (FL) percent eradication was achieved in
      T. rubrum groups. CONCLUSION: Photoactivation of Citrus EO increased the killing
      capability by 10-13%. A modest 7.5% augmented effect was observed with IR
      activation of Fluconazole. Both Citrus EO and photothermal-photodynamic therapy
      with ICG and IR diode laser exhibited remarkable lethal effect on fungal cells.
      Candida viable cells are more susceptible to laser only and ICG only treatments
      than Tricophyton cells.

PMID- 25573287
TI  - Mutational profiling of therapy-related myelodysplastic syndromes and acute
      myeloid leukemia by next generation sequencing, a comparison with de novo
      diseases.
AB  - In this study we used a next generation sequencing-based approach to profile gene
      mutations in therapy-related myelodysplastic syndromes (t-MDS) and acute myeloid
      leukemia (t-AML); and compared these findings with de novo MDS/AML. Consecutive
      bone marrow samples of 498 patients, including 70 therapy-related (28 MDS and 42
      AML) and 428 de novo (147 MDS and 281 AML) were analyzed using a modified-TruSeq
      Amplicon Cancer Panel (Illumina) covering mutation hotspots of 53 genes. Overall,
      mutation(s) were detected in 58.6% of t-MDS/AML and 56.8% of de novo MDS/AML. Of
      therapy-related cases, mutations were detected in 71.4% of t-AML versus 39.3% t
      MDS (p=0.0127). TP53 was the most common mutated gene in t-MDS (35.7%) as well as
      t-AML (33.3%), significantly higher than de novo MDS (17.7%) (p=0.0410) and de
      novo AML (12.8%) (p=0.0020). t-AML showed more frequent PTPN11 but less NPM1 and
      FLT3 mutations than de novo AML. In summary, t-MDS/AML shows a mutation profile
      different from their de novo counterparts. TP53 mutations are highly and
      similarly prevalent in t-MDS and t-AML but mutations in genes other than TP53
      were more frequent in t-AML than t-MDS. The molecular genetic profiling further
      expands our understanding in this group of clinically aggressive yet
      heterogeneous myeloid neoplasms. 

PMID- 25573288
TI  - Discriminant accuracy of a semantics measure with Latino English-speaking,
      Spanish-speaking, and English-Spanish bilingual children.
AB  - We explored classification accuracy of English and Spanish versions of an
      experimental semantic language measure with functional monolingual-bilingual
      children with and without language impairment. A total of 441 children
      participated, including 78 balanced bilinguals (15 with language impairment, 63
      with typical development); 179 monolingual Spanish (36 with language impairment,
      143 with typical development); and 183 monolingual English (49 with language
      impairment, 134 with typical development) children between 4;0 and 6;11 years.
      Cut points derived for functionally monolingual children were applied to
      bilinguals to assess the predictive accuracy of English and Spanish semantics.
      Correct classification of English monolinguals and Spanish monolinguals was 81%.
      Discriminant analysis yielded 76% and 90% correct classification for balanced
      bilingual children in English and Spanish respectively. This semantics-based
      measure has fair to good classification accuracy for functional monolinguals and
      for Spanish-English bilingual children when one language is tested. LEARNING
      OUTCOMES: As a result of this study, the reader will describe advantages of
      lexical-semantic tasks for identification of language impairment. They will be
      able to describe procedures for conceptual scoring and identify its benefits.
      Readers will also gain an understanding of similarities and differences in
      bilingual and monolingual performance on a semantics task in Spanish and English.

PMID- 25573290
TI  - No evidence for memory interference across sessions in food hoarding marsh tits
      Poecile palustris under laboratory conditions.
AB  - Scatter hoarding birds are known for their accurate spatial memory. In a previous
      experiment, we tested the retrieval accuracy in marsh tits in a typical
      laboratory set-up for this species. We also tested the performance of humans in
      this experimental set-up. Somewhat unexpectedly, humans performed much better
      than marsh tits. In the first five attempts, humans relocated almost 90 % of the
      caches they had hidden 5 h earlier. Marsh tits only relocated 25 % in the first
      five attempts and just above 40 % in the first ten attempts. Typically, in this
      type of experiment, the birds will be caching and retrieving many times in the
      same sites in the same experimental room. This is very different from the
      conditions in nature where hoarding parids only cache once in a caching site.
      Hence, it is possible that memories from previous sessions will disturb the
      formation of new memories. If there is such proactive interference, the
      prediction is that success should decay over sessions. Here, we have designed an
      experiment to investigate whether there is such memory interference in this type
      of experiment. We allowed marsh tits and humans to cache and retrieve in three
      repeated sessions without prior experience of the arena. The performance did not
      change over sessions, and on average, marsh tits correctly visited around 25 % of
      the caches in the first five attempts. The corresponding success in humans was
      constant across sessions, and it was around 90 % on average. We conclude that the
      somewhat poor performance of the marsh tits did not depend on proactive memory
      interference. We also discuss other possible reasons for why marsh tits in
      general do not perform better in laboratory experiments.

PMID- 25573289
TI  - Social referencing and cat-human communication.
AB  - Cats' (Felis catus) communicative behaviour towards humans was explored using a
      social referencing paradigm in the presence of a potentially frightening object.
      One group of cats observed their owner delivering a positive emotional message,
      whereas another group received a negative emotional message. The aim was to
      evaluate whether cats use the emotional information provided by their owners
      about a novel/unfamiliar object to guide their own behaviour towards it. We
      assessed the presence of social referencing, in terms of referential looking
      towards the owner (defined as looking to the owner immediately before or after
      looking at the object), the behavioural regulation based on the owner's emotional
      (positive vs negative) message (vocal and facial), and the observational
      conditioning following the owner's actions towards the object. Most cats (79 %)
      exhibited referential looking between the owner and the object, and also to some
      extent changed their behaviour in line with the emotional message given by the
      owner. Results are discussed in relation to social referencing in other species
      (dogs in particular) and cats' social organization and domestication history.

PMID- 25573291
TI  - [Intestinal spirochetosis: A rare cause of chronic diarrhea].

PMID- 25573292
TI  - Expression of interleukin-6 is associated with epithelial-mesenchymal transition
      and survival rates in gallbladder cancer.
AB  - The present study aimed to investigate the expression of interleukin-6 (IL-6) in
      gallbladder cancer (GBC) tissues and its correlation with survival rate. The
      association between IL-6 and epithelial-mesenchymal transition (EMT)-associated
      markers was also examined. Using immunohistochemistry, reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, the
      protein and mRNA expression levels of IL-6, Twist, E-cadherin and Vimentin in 20
      GBC tissues were analyzed. The IL-6, Twist and Vimentin proteins were
      overexpressed in 40, 20 and 70% of the human GBC samples, respectively. The
      protein expression of E-cadherin was higher in only 5% of the GBC samples. These
      differences were significant (P<0.05). Western blot analysis also revealed
      overexpression of IL-6, Twist and Vimentin and underexpression of E-cadherin in
      the GBC samples with poor differentiation, local invasion and a higher tumor-node
      metastasis (TNM) stage (P<0.05). Higher mRNA expression levels of IL-6, Twist and
      Vimentin and a reduced expression level of E-cadherin were also demonstrated in
      the GBC tissues (P<0.05). The degree of differentiation, local invasion, lymph
      node metastasis and clinical stage were significantly associated with the mRNA
      expression levels of IL-6, Twist and E-cadherin. The increased expression levels
      of IL-6 and Twist and the reduced expression of E-cadherin correlated with
      shorter median survival rates (P<0.05). Line regression results revealed
      correlation among the mRNA expression levels of IL-6, Twist, E-cadherin and
      Vimentin. To the best of our knowledge, the present study is the first to
      demonstrate that IL-6 is associated with EMT-associated markers, tumor
      differentiation, local invasion, TNM stage and survival rates in GBC.

PMID- 25573293
TI  - Alpha-MMC and MAP30, two ribosome-inactivating proteins extracted from Momordica
      charantia, induce cell cycle arrest and apoptosis in A549 human lung carcinoma
      cells.
AB  - alpha-Momorcharin (alpha-MMC) and momordica anti-human immunodeficiency virus
      protein (MAP30), produced by Momordica charantia, are ribosome-inactivating
      proteins, which have been reported to exert inhibitory effects on cultured tumor
      cells. In order to further elucidate the functions of these agents, the present
      study aimed to investigate the effects of alpha-MMC and MAP30 on cell viability,
      the induction of apoptosis, cell cycle arrest, DNA integrity and superoxide
      dismutase (SOD) activity. alpha-MMC and MAP30 were purified from bitter melon
      seeds using ammonium sulfate precipitation in combination with sulfopropyl (SP)
      sepharose fast flow, sephacryl S-100 and macro-Cap-SP chromatography. MTT, flow
      cytometric and DNA fragmentation analyses were then used to determine the effects
      of alpha-MMC and MAP30 on human lung adenocarcinoma epithelial A549 cells. The
      results revealed that A549 cells were sensitive to alpha-MMC and MAP30
      cytotoxicity assays in vitro. Cell proliferation was significantly suppressed
      following alpha-MMC and MAP30 treatment in a dose- and time-dependent manner; in
      addition, the results indicated that MAP30 had a more potent anti-tumor activity
      compared with that of alpha-MMC. Cell cycle arrest in S phase and a significantly
      increased apoptotic rate were observed following treatment with alpha-MMC and
      MAP30. Furthermore, DNA integrity analysis revealed that the DNA of A549 cells
      was degraded following treatment with alpha-MMC and MAP30 for 48 h. The
      pyrogallol autoxidation method and nitrotetrazolium blue chloride staining were
      used to determine SOD activity, the results of which indicated that alpha-MMC and
      MAP30 did not possess SOD activity. In conclusion, the results of the present
      study indicated that alpha-MMC and MAP30 may have potential as novel therapeutic
      agents for the prophylaxis and treatment of cancer.

PMID- 25573294
TI  - Metal-free ring-opening metathesis polymerization.
AB  - We have developed a method to achieve ring-opening metathesis polymerization
      (ROMP) mediated by oxidation of organic initiators in the absence of any
      transition metals. Radical cations, generated via one-electron oxidation of vinyl
      ethers, were found to react with norbornene to give polymeric species with
      microstructures essentially identical to those traditionally obtained via metal
      mediated ROMP. We found that vinyl ether oxidation could be accomplished under
      mild conditions using an organic photoredox mediator. This led to high yields of
      polymer and generally good correlation between M(n) values and initial monomer to
      catalyst loadings. Moreover, temporal control over reinitiation of polymer growth
      was achieved during on/off cycles of light exposure. This method demonstrates the
      first metal-free method for controlled ROMP.

PMID- 25573296
TI  - Emotional processes in patients undergoing coronary artery bypass graft surgeries
      with extracorporeal circulation in view of selected indicators of the
      inflammatory condition.
AB  - BACKGROUND: The aim of this study was to describe positive and negative emotions
      in patients undergoing coronary artery bypass graft (CABG) surgeries with
      extracorporeal circulation and the correlations between emotions and basic
      indicators of the inflammatory condition: C-reactive protein (CRP) concentration,
      body temperature, and leukocyte count. MATERIAL/METHODS: Standardized tools were
      used to select 52 patients (aged 47-63 years, 6 women--11.5% and 46 men--88.5%)
      without dementia or depression. The Positive and Negative Affect Schedule (PANAS)
      was used to examine positive affect (PA) and negative affect (NA) and the State
      Trait Anxiety Inventory (STAI X1 and X2) was used to examine the anxiety level.
      The patients underwent CABG surgery according to a common anesthesia protocol and
      for 5 consecutive days they were observed in the ward, where selected indicators
      of the inflammatory condition were monitored. RESULTS: A detailed description of
      the results of examinations of emotions was presented. The patients with low PA
      trait level, high NA-trait level, and high anxiety-trait level (STAI X2)
      exhibited statistically significantly higher body temperatures than the other
      patients in the postoperative period. The patients with high NA-trait and anxiety
      state levels (STAI X1) had statistically significantly lower CRP levels in the
      postoperative period than the patients with low NA-trait and anxiety-state levels
      (STAI X1). CONCLUSIONS: Patients undergoing CABG operations express both positive
      and negative affects. The changes in the inflammatory markers are expressed
      mostly by CRP concentration. There exist relationships between the result of
      tests assessing emotions and the markers of the inflammatory condition.

PMID- 25573297
TI  - Game of isoforms: PI3K beta-sparing inhibitor is coming.

PMID- 25573295
TI  - Brown and beige fat: the metabolic function, induction, and therapeutic
      potential.
AB  - Adipose tissue is an important organ for energy homeostasis. White adipose tissue
      stores energy in the form of triglycerides, whereas brown adipocytes and recently
      identified beige adipocytes are specialized in dissipating energy by
      thermogenesis or contribution to dispose glucose and clear triglycerides in
      blood. The inverse correlation between the brown adipose tissue activity and body
      mass suggests its protective role against body fat accumulation. Thus,
      recruitment and activation of brown or beige adipose tissue become particularly
      appealing targets for increasing energy expenditure. Angiogenesis and sympathetic
      nerve signals are the fundamental determinants for brown and beige adipose tissue
      development, as well as for their metabolic functions. Secretary factors
      including BMPs can induce the development, the activation of brown or beige
      adipose tissue, which seem to be promising for therapeutic development. 

PMID- 25573299
TI  - SKI-1/S1P inhibitor PF-429242 impairs the onset of HCV infection.
AB  - Worldwide, approximately 170 million individuals are afflicted with chronic
      hepatitis C virus (HCV) infection. To prevent the development of inherent
      diseases such as cirrhosis and hepatocellular carcinoma, tremendous efforts have
      been made, leading to the development of promising new treatments. However, their
      efficiency is still dependent on the viral genotype. Additionally, these
      treatments that target the virus directly can trigger the emergence of resistant
      variants. In a previous study, we have demonstrated that a long-term (72h)
      inhibition of SKI-1/S1P, a master lipogenic pathway regulator through activation
      of SREBP, resulted in impaired HCV genome replication and infectious virion
      secretion. In the present study, we sought to investigate the antiviral effect of
      the SKI-1/S1P small molecule inhibitor PF-429242 at the early steps of the HCV
      lifecycle. Our results indicate a very potent antiviral effect of the inhibitor
      early in the viral lifecycle and that the overall action of the compound relies
      on two different contributions. The first one is SREBP/SKI-1/S1P dependent and
      involves LDLR and NPC1L1 proteins, while the second one is SREBP independent.
      Overall, our study confirms that SKI-1/S1P is a relevant target to impair HCV
      infection and that PF-429242 could be a promising candidate in the field of HCV
      infection treatment. 

PMID- 25573301
TI  - Epidemiological voice health map of the teaching population of Granollers
      (Barcelona) developed from the EVES questionnaire and the VHI.
AB  - The aim of this research project was to carry out an epidemiological study on the
      voice health of the teaching population in Granollers (Barcelona) using the EVES
      questionnaire and to relate the collected data to the VHI results. The study
      sample consisted of 233 teachers from Granollers (Barcelona). The EVES
      questionnaire, which includes the VHI-10, was conducted online. A high percentage
      of the teachers consulted suffered voice disorders, which ranged from minor to
      more serious cases. In regard to the data obtained using the VHI, in 28.77% of
      the cases there was a moderate or a serious perception of voice problems. Out of
      these cases only one person, who had a moderate perception of their problem, was
      undergoing voice therapy with a speech therapist. There are three questions in
      the EVES questionnaire that can efficiently indicate the existence of a voice
      disorder in a straightforward manner, and the results for these were similar to
      those recorded for the VHI group of questions. Therefore, it may be argued that
      questions that refer to the perception of the degree of pleasantness of one's own
      voice should be included, because they would provide a useful way to indicate
      whether there is a voice problem at a preliminary screening stage. 

PMID- 25573298
TI  - The effects of sigma (sigma1) receptor-selective ligands on muscarinic receptor
      antagonist-induced cognitive deficits in mice.
AB  - BACKGROUND AND PURPOSE: Cognitive deficits in patients with Alzheimer's disease,
      Parkinson's disease, traumatic brain injury and stroke often involve alterations
      in cholinergic signalling. Currently available therapeutic drugs provide only
      symptomatic relief. Therefore, novel therapeutic strategies are needed to retard
      and/or arrest the progressive loss of memory. EXPERIMENTAL APPROACH: Scopolamine
      induced memory impairment provides a rapid and reversible phenotypic screening
      paradigm for cognition enhancement drug discovery. Male C57BL/6J mice given
      scopolamine (1 mg.kg(-1) ) were used to evaluate the ability of LS-1-137, a novel
      sigma (sigma1) receptor-selective agonist, to improve the cognitive deficits
      associated with muscarinic antagonist administration. KEY RESULTS: LS-1-137 is a
      high-affinity (Ki = 3.2 nM) sigma1 receptor agonist that is 80-fold selective for
      sigma1, compared with sigma2 receptors. LS-1-137 binds with low affinity at D2
      like (D2, D3 and D4) dopamine and muscarinic receptors. LS-1-137 was found to
      partially reverse the learning deficits associated with scopolamine
      administration using a water maze test and an active avoidance task. LS-1-137
      treatment was also found to trigger the release of brain-derived neurotrophic
      factor from rat astrocytes. CONCLUSIONS AND IMPLICATIONS: The sigma1 receptor
      selective compound LS-1-137 may represent a novel candidate cognitive enhancer
      for the treatment of muscarinic receptor-dependent cognitive deficits.

PMID- 25573300
TI  - Lymphocyte senescence in COPD is associated with loss of glucocorticoid receptor
      expression by pro-inflammatory/cytotoxic lymphocytes.
AB  - BACKGROUND: Glucocorticoid (GC) resistance is a major barrier in COPD treatment.
      We have shown increased expression of the drug efflux pump, Pgp1 in cytotoxic/pro
      inflammatory lymphocytes in COPD. Loss of lymphocyte co-stimulatory molecule CD28
      (lymphocyte senescence) was associated with a further increase in their pro
      inflammatory/cytotoxic potential and resistance to GC. We hypothesized that
      lymphocyte senescence and increased Pgp1 are also associated with down-regulation
      of the GC receptor (GCR). METHODS: Blood was collected from 10 COPD and 10
      healthy aged-matched controls. Flow cytometry was applied to assess intracellular
      pro-inflammatory cytokines, CD28, Pgp1, GCR, steroid binding and relative
      cytoplasm/nuclear GCR by CD28+ and CD28null T, NKT-like cells. GCR localization
      was confirmed by fluorescent microscopy. RESULTS: COPD was associated with
      increased numbers of CD28nullCD8+ T and NKT-like cells. Loss of CD28 was
      associated with an increased percentage of T and NKT-like cells producing
      IFNgamma or TNFalpha and associated with a loss of GCR and Dex-Fluor staining but
      unchanged Pgp1. There was a significant loss of GCR in CD8 + CD28null compared
      with CD8 + CD28+ T and NKT-like cells from both COPD and controls (eg, mean +/-
      SEM 8 +/- 3% GCR + CD8 + CD28null T-cells vs 49 +/- 5% GCR + CD8 + CD28+ T-cells
      in COPD). There was a significant negative correlation between GCR expression and
      IFNgamma and TNFalpha production by T and NKT-like cells(eg, COPD: T-cell
      IFNgamma R = -.615; ) and with FEV1 in COPD (R = -.777). CONCLUSIONS: COPD is
      associated with loss of GCR in senescent CD28null and NKT-like cells suggesting
      alternative treatment options to GC are required to inhibit these pro
      inflammatory/cytotoxic cells.

PMID- 25573302
TI  - Variants in SELL, MRPS36P2, TP63, DDB2, CACNA1H, ADAM19, GNAI1, CDH13 and GABRG2
      interact to confer risk of acne in Chinese population.
AB  - Acne vulgaris is a common skin disease characterized by chronic inflammation of
      the pilosebaceous unit resulting from androgen-induced increased sebum
      production, altered keratinization, inflammation and bacterial colonization of
      hair follicles by propionibacterium acnes. Our previous genome-wide association
      study on acne has identified two new susceptibility loci. To search for potential
      gene-gene interactions and investigate the best-fit association models for the
      single nucleotide polymorphisms (SNP) from these interacting genes, we
      implemented logistic regression analysis in the combined sample of 2916 cases
      with severe acne and 4716 controls. The most significant association evidence was
      observed under an additive model for rs6896064 and under a dominant model the
      rest of these SNP. Significant interactions between these SNP were observed in
      this study: the SELL * MRPS36P2 (Padjusted = 4.15 * 10(-10)), TP63 * DDB2
      (Padjusted = 7.62 * 10(-08)), DDB2 * CACNA1H (Padjusted = 1.89 * 10(-07)), ADAM19
      * GNAI1 * CDH13 (Padjusted = 1.22 * 10(-04)) and ADAM19 * GABRG2 * GNAI2 * CDH13
      (Pad justed = 6.33 * 10(-05)). These results may contribute to our understanding
      of acne genetic etiology and account for the additional risk of certain patients.

PMID- 25573303
TI  - The new Scandinavian Donations and Transfusions database (SCANDAT2): a blood
      safety resource with added versatility.
AB  - BACKGROUND: Risks of transfusion-transmitted disease are currently at a record
      low in the developed world. Still, available methods for blood surveillance might
      not be sufficient to detect transmission of diseases with unknown etiologies or
      with very long incubation periods. STUDY DESIGN AND METHODS: We have previously
      created the anonymized Scandinavian Donations and Transfusions (SCANDAT)
      database, containing data on blood donors, blood transfusions, and transfused
      patients, with complete follow-up of donors and patients for a range of health
      outcomes. Here we describe the re-creation of SCANDAT with updated, identifiable
      data. We collected computerized data on blood donations and transfusions from
      blood banks covering all of Sweden and Denmark. After data cleaning, two
      structurally identical databases were created and the entire database was linked
      with nationwide health outcomes registers to attain complete follow-up for up to
      47 years regarding hospital care, cancer, and death. RESULTS: After removal of
      erroneous records, the database contained 25,523,334 donation records, 21,318,794
      transfusion records, and 3,692,653 unique persons with valid identification,
      presently followed over 40 million person-years, with possibility for future
      extension. Data quality is generally high with 96% of all transfusions being
      traceable to their respective donation(s) and a very high (>97%) concordance with
      official statistics on annual number of blood donations and transfusions.
      CONCLUSIONS: It is possible to create a binational, nationwide database with
      almost 50 years of follow-up of blood donors and transfused patients for a range
      of health outcomes. We aim to use this database for further studies of donor
      health, transfusion-associated risks, and transfusion-transmitted disease.

PMID- 25573305
TI  - [Dual transplant: a new approach for improving the outcome of hematopoietic stem
      cell transplantation].

PMID- 25573306
TI  - [Long-term complications of patients after endoscopic sphincterotomy for
      choledocholithiasis].

PMID- 25573304
TI  - Comparative in vitro mechanical evaluation of techniques using a 2.0 mm locking
      fixation system for simulated fractures of the mandibular body.
AB  - PURPOSE: To perform a comparative evaluation of the mechanical resistance of
      simulated fractures of the mandibular body which were repaired using different
      fixation techniques with two different brands of 2.0 mm locking fixation systems.
      MATERIALS AND METHODS: Four aluminum hemimandibles with linear sectioning
      simulating a mandibular body fracture were used as the substrates and were fixed
      using the two techniques and two different brands of fixation plate. These were
      divided into four groups: groups I and II were fixed with one four-hole plate,
      with four 6 mm screws in the tension zone and one four-hole plate, with four 10
      mm screws in the compression zone; and groups III and IV were fixed with one four
      hole plate with four 6 mm screws in the neutral zone. Fixation plates
      manufactured by Toride were used for groups I and III, and by Traumec for groups
      II and IV. The hemimandibles were submitted to vertical, linear load testing in
      an Instron 4411 servohydraulic mechanical testing unit, and the load/displacement
      (3 mm, 5 mm and 7 mm) and the peak loads were measured. Means and standard
      deviations were evaluated applying variance analysis with a significance level of
      5%. RESULTS: The only significant difference between the brands was seen at
      displacements of 7 mm. Comparing the techniques, groups I and II showed higher
      mechanical strength than groups III and IV, as expected. CONCLUSION: For the
      treatment of mandibular linear body fracture, two locking plates, one in the
      tension zone and another in the compression zone, have a greater mechanical
      strength than a single locking plate in the neutral zone.

PMID- 25573307
TI  - [Clinical outcomes of allogeneic hematopoietic stem cell transplantation patients
      with co-activation of cytomegalovirus and Epstein-Barr virus].
AB  - OBJECTIVE: To evaluate the impact of cytomegalovirus (CMV) and Epstein-Barr virus
      (EBV) co-activation on the prognosis of allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) patients. METHODS: We retrospectively analyzed 330
      consecutive allo-HSCT patients at First Affiliated Hospital of Soochow University
      from December 2011 to August 2013. CMV and EBV DNA were regularly monitored by
      quantitative polymerase chain reaction (PCR) from the engraftment of granuloCyte
      within one year after transplantation. The incidences of viremia and clinical
      outcomes were analyzed by chi(2) test and Kaplan-Meier analysis. RESULTS: After a
      median follow-up period of 16 (7-25) months, a total of 113 (34.2%) patients were
      identified with CMV viremia (CMV+) alone, 82 (24.8%) with EBV viremia (EBV+)
      alone and 32 (9.7%) with CMV and EBV co-activation (CMV/EBV+). The proportion of
      patients undergoing HLA mismatched transplantation and ones with acute graft
      versus-host disease (aGVHD) in CMV/EBV+ group was significantly higher than CMV+
      group or EBV+ group (78.1% (25/32) vs 58.5% (48/82) or 50.4% (57/113), P =
      0.047,0.008; 56.3% (18/32) vs 32.9% (27/82) or 34.5% (39/113) , P = 0.022, 0.026)
      . The incidence of post-transplant lymphoproliferative disorder (PTLD) was
      similar to EBV+ group (12.5% (4/32) vs 11.0% (9/82) , P = 0.802) and so did the
      incidence of CMV disease when compared with CMV+ group (9.4% (3/32) vs 7.1%
      (8/113) , P = 0.665). The 2-year overall survival (OS) of CMV+, EBV+ and CMV/EBV+
      groups was 68.7%, 61.5% and 62.4% respectively. And no significant difference
      existed between CMV/EBV+ and the other two groups (P = 0.598, 0.717). However,
      the 6-month non-relapse mortality (NRM) of CMV/EBV+ group was significantly
      higher than that of CMV+ or EBV+ group (18.7% vs 8.9%, P = 0.036; 18.7% vs 8.1%,
      P = 0.032). CONCLUSIONS: HLA mismatch transplants and aGVHD are frequent in CMV
      and EBV co-activation group. When compared with EBV+ or CMV+ patients, the
      CMV/EBV+ patients have similar incidence of PTLD or CMV disease and 2-year
      OS.However, the 6-month NRM is significantly higher in CMV/EBV+ group. It
      suggests that CMV and EBV co-activation is a risk factor for early mortality of
      allo-HSCT patients.

PMID- 25573308
TI  - [Efficacies of hematopoietic stem cell transplantation for severe aplastic
      anemia: a report of 43 patients].
AB  - OBJECTIVE: To evaluate the efficacies of hematopoietic stem cell transplantation
      (HSCT) for severe aplastic anemia (SAA). METHODS: A total of 43 SAA patients (SAA
      I, n = 29; SAA-II, n = 14) underwent HSCT from 2002 January to 2013 December.
      There were 22 males and 21 females with a median age of 31 (12-49) years. And 35
      patients received HLA-matched sibling HSCT (Sib-HSCT) while another 8 had
      unrelated donor HSCT (UD-HSCT). The hematopoietic stem cells were collected from
      bone marrow (n = 10), peripheral blood (n = 23) and bone marrow & peripheral
      blood (n = 10). Conditioning regimens were mostly composed of Fludarabine,
      antihuman thymocyte gloBulin and cyclophosphamide. Cyclosporine and methotrexate
      (including mycophenolate mofetil for UD) were offered for preventing graft-versus
      host disease (GVHD). The median counts of mononuclear cell and CD34(+) stem cell
      were 8.1 (2.4-13.5) *10(8)/kg and 3.7 (2.3-14.7) *10(6)/kg respectively. RESULTS:
      Hematopoiesis reconstitution was achieved in 42 patients. The median periods for
      neutrophils to 0.5*10(9)/L and platelets to 20*10(9)/L were +10 (+8-+25) days and
      +14 (+8-+80) days respectively. The median of survival time was not reached.
      Overall survival (OS) and failure-free survival (FFS) at 5 years had no
      differences between UD-HSCT and Sib-HSCT groups (OS: 87.6% vs 84.5%, P = 0.87;
      FFS: 86.2% vs 79.5%, P = 0.64). The same results also were seen between age <= 20
      group and > 20 group (OS: 92.0% vs 82.5%, P = 0.39; FFS: 91.0% vs 77.3%, P =
      0.38). The median follow-up time was 17.0 (0.4-140.0) months. And 8/43 patients
      died from thrombotic microangiopathy (TMA) (n = 1), TMA associated with capillary
      leak syndrome (n = 1), pulmonary infection (n = 3), acute GVHD of grade IV (n =
      1) and unknown causes (n = 2). CONCLUSIONS: Sib-HSCT is preferred for SAA
      patients under 40 years. Searching of HLA-matched unrelated donor should be
      performed soon after diagnosis if HLA-matched sibling is unavailable.

PMID- 25573309
TI  - [Cytomegalovirus infection monitoring in patients with long-term survival after
      allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To analyze the cytomegalovirus (CMV) infection status and the risk
      factors in patients with long-term survival after allogeneic hematopoietic stem
      cell transplantation (allo-HSCT). METHODS: 159 long-term survivors receive allo
      HSCT from January 2008 through December 2011 in the Bone Marrow Transplantation
      Center of Zhejiang University were included, CMV-pp65 antigen in peripheral blood
      leukocytes was detected by immunofluorescence assay at regular intervals, to
      retrospectively analyzed the clinical data. Ganciclovir or foscarnet was used for
      prevent and curative therapy. RESULTS: A total of 159 patients with long-term
      survival at 18-66 months after allo-HSCT were investigated. And 8 047 specimens
      were detected, including 2 553 positive samples. All patients were at least one
      time positive for CMV-pp65 antigen after allo-HSCT. The CMV antigen positive rate
      increased gradually from 100 days after transplantation to within 100 days until
      1 year while the positive rate decreased, after 1 year. The difference was
      statistically significant (all P < 0.01). The CMV antigen positive rate in
      patients after non-myeloablative allo-HSCT (NST) and those after myeloablative
      allo-HSCT were 167/608(27.5%) and 2 386/7 439 (32.1%) respectively. The
      difference was statistically significant (P = 0.019). No statistically
      significant difference existed between those with acute graft-versus-host disease
      (aGVHD) and chronic graft-versus-host disease (cGVHD) (both P > 0.05). The CMV
      antigen positive rate in patients with I-IIgrade aGVHD and those with III-IV
      grade aGVHD were 1 017/3 284(31.0%) and 227/641(35.4%) respectively. And it had
      statistically significant difference (P = 0.027). The CMV antigen positive rate
      in patients none-used of ATG and those used of ATG were 1 255/3 755 (33.4%) and 1
      298/4 292 (30.2%) respectively. And it had statistically significant difference
      (P = 0.002). By Logistic multivariate analysis, the none-use of ATG and III-IV
      grade aGVHD were the risk factors for CMV antigen positive after allo-HSCT (OR =
      1.174, 95%CI:1.068-1.290, P = 0.001;OR = 1.174, 95%CI:0.681-0.958, P = 0.014).
      CONCLUSIONS: Regular monitoring of CMV-pp65 antigen after allo-HSCT is quite
      necessary for prevent and treat CMV infection in a timely manner. The CMV
      infection in long-term survival patients may be related to the selection of
      conditioning regimen, it has no obvious correlation with the incidence of GVHD,
      but it is associated with the severity of aGVHD.

PMID- 25573310
TI  - [Allo-geneic hematopoietic stem cell transplantation in treatment with T315I
      mutation of chronic myelogenous leukemia].
AB  - OBJECTIVE: To explore the therapeutic efficacy of allo-geneic hematopoietic stem
      cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML) patients
      with T315I mutation. METHODS: Retrospective analyses were conducted for 4
      patients with T315I mutation of CML undergoing allo-HSCT from June 2012 to
      January 2014, including 2 cases in acceleration phase and 2 in chronic phase.
      There were 2 males and 2 females with ages from 26 to 45 years. Two patients
      received HLA-matched sibling allo-geneic peripheral blood stem cell
      transplantation (allo-PBSCT) while another 2 unrelated cord blood stem cell
      transplantation (UCBT). No splenomegaly was found before transplantation. One
      case had F317L mutation. All of them were treated with imatinib before
      transplantation. And the time from medication to T315I mutation was 20-35 months.
      All of them were conditioned with myeloablative regimen and received a
      combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for
      preventing graft-versus-host disease (GVHD). RESULTS: Myeloid implantation was
      achieved in all of them. The time of absolute neutrophil count (ANC) >=
      0.5*10(9)/L were 10-28 days. One patient whose platelet was not implanted died
      from severe pulmonary infection at Day 88 post-transplantation. For 3 patients,
      platelet >= 20*10(9)/L were 15-33 days. But the marrow short tandem repeat (STR)
      PCR was 100% donor type at the time of 30 days post-transplantation in all
      patients. One case of UCBT developed pre-implantation immune response syndrome
      (PES) and one acute GVHD of gradeI at Day 12 after allo-PBSCT. However both were
      controlled after treatment with methylprednisolone. And 1/3 evaluatable patients
      developed chronic GVHD. BCR/ABL transcript was detected by qualitative PCR after
      transplantation. And all BCR/ABL fusion genes turned negative after 30 days of
      transplantation. Up to the follow-up endpoint, there was no relapse except for
      one mortality. And the time of disease-free survival was 133, 248 and 704 days
      respectively. CONCLUSIONS: Allo-HSCT is currently the optimal treatment for T315I
      mutation of CML. And umbilical cord blood is an ideal donor for those patients
      without HLA-matched sibling donor.

PMID- 25573311
TI  - [Differential concentrations of conjugated bile acids in sera of patients with
      polypoid lesions of gallbladder].
AB  - OBJECTIVE: To explore the concentration differences of eight conjugated bile
      acids between patients of cholesterol polyps and adenomatous polyps and determine
      the differential diagnosis markers for polypoid lesions of gallbladder (PLG).
      METHODS: During the period of March 2013 to November, 18 cholesterol polyps
      patients, 9 adenomatous polyps ones and 20 simple gallstone disease ones were
      enrolled. High performance liquid chromatography with ultraviolet detection was
      used to test 8 conjugated bile acids in sera. RESULTS: A total of 8 conjugated
      bile acids were completely dissociated within 10 minutes and the assay was liner
      in the range of 3.91 to 500.00 mg/L. The correlation coefficients for linear
      regression were from 0.995 to 0.999 and the detection limits ranged from 3.91 to
      7.81 mg/L. The serum level of glycocholic acid (GCA) in adenomatous polyps group
      (3.48 +/- 1.66) mg/L was significantly higher than that in cholesterol polyps
      group ((2.16 +/- 0.71) mg/L, q = 5.182, P = 0.001) and control group ((2.15 +/-
      0.45) mg/L, q = 5.313, P = 0.001). The serum level of glycochenodeoxycholic acid
      (GCDCA) in adenomatous polyps group (12.67 +/- 1.74) mg/L was significantly
      higher than that in cholesterol polyps group ((10.53 +/- 3.04) mg/L, q = 3.253, P
      = 0.026) and control group ((10.72 +/- 1.58) mg/L, q = 3.015, P = 0.038). The
      serum level of taurochenodeoxycholic acid (TCDCA) in adenomatous polyps group
      ((6.79 +/- 2.90) mg/L) was significantly higher than that in cholesterol polyps
      group ((4.47 +/- 2.35) mg/L, q = 3.412, P = 0.020) and control group ((4.72 +/-
      2.11) mg/L q = 3.091, P = 0.034). CONCLUSION: The serum levels of GCA, GCDCA and
      TCDCA in adenomatous polyps patients are higher than those in cholesterol polyps
      counterparts. And these markers may aid the differential diagnosis of PLG.

PMID- 25573312
TI  - [Treatment of unexpected gallbladder carcinoma after laparoscopic
      cholecystectomy].
AB  - OBJECTIVE: To summarize the clinical features and diagnostic and therapeutic
      experiences of unexpected gallbladder carcinoma (UGC) during or after
      laparoscopic cholecystectomy (LC) to boost radical resection rate and long-term
      efficacy. METHODS: The clinical data of 64 UGC patients undergoing LC were
      retrospectively analyzed. RESULTS: The procedures included LC (n = 28) and LC
      plus radical resection (n = 36). The follow-up period was 2-132 months. The inter
      group differences were statistically significant in post-operative survival rate
      (35 vs 46 months, P < 0.05). According to the TNM staging system, the post
      operative survival rate between two groups for pTis+pT1a grade was not
      statistically significant (84 vs 132 months, P > 0.05).However the differences
      for pT1b, pT2 and pT3 grades were statistically significant (43 vs 86 months; 31
      vs 52 months; 18 vs 36 months, P < 0.05). CONCLUSIONS: Identification of high
      risk factors and intraoperative rapid pathologic examination improve radical
      resection rate.Radical cure via LC may be achieved for pTis and pT1a stages of
      UGC.For pT1b stage of UGC, optimal surgical procedures need further
      explorations.For stages pT2 and pT3 of UGC, radical surgery should be added for
      improved long-term efficacies.

PMID- 25573313
TI  - [Anti-tumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line in
      vitro].
AB  - OBJECTIVE: To explore the antitumor effects of DDP-PLLA-CNTs on human
      cholangiocarcinoma cell line. METHODS: DDP-PLLA-CNTs were prepared with the
      method of ultrasound emulsification. The morphology of DDP-PLLA-CNTs was
      determined by scanning electron microscope (SEM). And its drug loading and drug
      release curve in vitro was detected by UV-Vis-NIR spectrophotometer. CCK8 was
      used to test the cytotoxic effects of DDP-PLLA-CNTs at different concentrations
      on QBC939 cell proliferation.Flow cytometry was employed to measure the changes
      of apoptotic rate. RESULTS: With excellent controlled-release characteristic of
      in vitro drug release, DDP-PLLA-CNTs inhibited the proliferation and
      significantly increased the apoptotic rate of QBC939 cell line. CONCLUSION: DDP
      PLLA-CNTs have drug sustained-release characteristics and can significantly
      inhibit the proliferation of QBC939 cell line.

PMID- 25573314
TI  - [Evaluation of pleth variability index for predicting hypotension during
      induction of anesthesia in surgical patients].
AB  - OBJECTIVE: To evaluate the ability of pre-anesthesia pleth variability index
      (PVI) in supine and passive head raising (PHR) position at 30 degrees  for
      predicting hypotension during induction of anesthesia. METHODS: From September
      2012 to October 2013, 106 patients scheduled for elective surgery under general
      anesthesia at Third Hangzhou Municipal Hospital with American Society of
      Anesthesiologists I-II were recruited. Pre-anesthesia values of blood pressure,
      heart rate, perfusion index, PVI in supine position and PHR at 30 degrees  were
      recorded. The minimum arterial blood pressure and minimum heart rate during
      anesthesia induction were recorded. RESULTS: Blood pressure and heart rate
      significantly decreased after induction. And the decline ratio of diastolic
      arterial blood pressure and mean arterial blood pressure were moderately
      correlated with pre-anesthesia PVI at 30 degrees  PHR position with Pearson's
      coefficients of 0.492 and 0.463 respectively. The receiver-operating
      characteristic curve demonstrated that pre-anesthesia PVI in PHR at 30 degrees 
      position could predict hypotension during induction with a sensitivity of 67% and
      a specificity of 62% whereas pre-anesthesia PVI in supine position was non
      reliable in predicting hypotension. CONCLUSION: Pre-anesthesia PVI in PHR at 30
      degrees  position may predict hypotension during induction with an acceptable
      accuracy. And this procedure is probably helpful for assessing high-risk patients
      susceptible to severe hypotension during induction.

PMID- 25573315
TI  - [Clinical analyses of sarcoidosis with ocular involvement].
AB  - OBJECTIVE: To explore the clinical characteristics and systemic manifestations of
      sarcoidosis with ocular involvement. METHODS: The clinical data of 19 cases of
      sarcoidosis with ocular involvement confirmed by pathology at Beijing Tongren
      Hospital from March 2004 to February 2014 were analyzed retrospectively. The
      ocular manifestations, chest imaging findings, laboratory tests and pathological
      diagnosis were reviewed. And the clinical features of sarcoidosis with ocular
      involvement were summarized. RESULTS: Among them, there were 6 males and 13
      females with an average age of (47 +/- 14) (16-76) years. The ocular symptoms
      were the initial presenting manifestations of sarcoidosis in 12 cases while 2
      cases presented ocular symptoms during the course of disease. And aother 5 cases
      without ocular symptoms were confirmed to have ocular involvement by eye
      examination. The main manifestations of ocular sarcoidosis were uveitis (n = 16),
      chorioretinitis (n = 3), retinal vasculitis (n = 2), optic neuritis (n = 1) and
      orbital mass (n = 3). The key feature of sarcoidosis was bilateral hilar
      lymphadenopathy (BHL) (14/16) on chest film. The diagnosis in 17 cases was
      confirmed by biopsy of extra-ocular organs. The positive diagnostic rate of
      bronchial biopsy was 8/9. CONCLUSIONS: Ocular involvement in sarcoidosis is
      relatively common due to a variety of ocular manifestations and serious vision
      impairment in some patients. Ophthalmologic examination is essential in the
      clinical management of sarcoidosis. Chest imaging and bronchial biopsy are
      important for the diagnosis of sarcoidosis with initial ocular manifestations.

PMID- 25573316
TI  - [Reference interval in preliminary investigation of maternal thyroid function
      during pregnancy in Shenzhen China].
AB  - OBJECTIVE: To explore the thyroid function distribution of different trimesters
      among normal pregnant women and establish the reference interval for maternal
      thyroid function during pregnancy in Shenzhen, China. METHODS: A prospective
      study was conducted for healthy pregnant women in first trimester (n = 334),
      second trimester (n = 272), third trimester (n = 271) and non-pregnant controls
      (n = 77) from December 2012 to June 2013 at our hospital. Free triiodothyronine
      (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), triiodothyronine
      (TT3) and thyroxine (T4) of four groups were measured and analyzed. And the
      reference intervals for different trimesters were established. RESULTS: TSH
      declined in the first trimester and then rose in the second trimester. The
      reference ranges of TSH for early, middle and late pregnancy were 0.08-4.39, 0.41
      4.16 and 0.30-5.46 mIU/L respectively. FT4 and healthy control groups showed no
      significant difference in the first trimester. But it declined in the second
      trimester. The reference ranges of FT4 for early, middle and late pregnancy were
      7.74-14.58, 6.81-12.00 and 6.36-10.99 pmol/L respectively. FT3 rose slightly in
      the first trimester and then gradually decreased. The reference ranges of FT3 for
      early, middle and late pregnancy were 3.59-5.59, 3.34-4.91 and 3.09-4.58 pmol/L
      respectively. CONCLUSIONS: As compared with healthy control women in Shenzhen,
      thyroid function indicators of pregnant women show statistically significant
      differences. And the establishment of indicators of women's thyroid function
      reference intervals for different trimesters has important clinical significance
      in Shenzhen.

PMID- 25573317
TI  - [Protective effects of inhaled hydrogen gas on cognitive function in mice with
      sepsis-associated encephalopathy].
AB  - OBJECTIVE: To evaluate protective effects of inhaled hydrogen gas (H2) on
      cognitive function in a murine model of sepsis-associated encephalopathy (SAE).
      METHODS: A total of 84 male ICR mice, weighing 20-25 g, aged 6-8 weeks, were
      randomly divided into 4 groups of sham, sham+H2, sepsis and sepsis+H2. Sepsis was
      established by cecal ligation and puncture (CLP). Mice in sham+H2 and sepsis+H2
      groups received 2% H2 inhalation for 1 h at 1 h and 6 h after sham operation or
      CLP operation respectively. The changes of neurological function and neuronal
      damage in hippocampal CA1 region were observed at 24 h post-operation. The
      activities of superoxide dismutase (SOD) and catalase (CAT) and the levels of
      malondialdehyde (MDA) and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) in sera
      and hippocampus were detected at 24 h post-operation. The changes of cognitive
      function were observed by Y-maze test and fear conditional test at days 3 to 14
      post-operation. RESULTS: Compared with sham group, the neurological function
      significantly declined and neurons in hippocampal CA1 region were significantly
      damaged; the activities of SOD and CAT markedly decreased while the levels of MDA
      and 8-iso-PGF2alpha markedly increased in sera and hippocampus; the time in new
      zone and the percentage of freezing time dramatically decreased at days 3 to 14
      post-operation in sepsis group (P < 0.05) . Compared with sepsis group,
      neurological function significantly improved and damaged neurons in hippocampal
      CA1 region significantly reduced; the activities of SOD and CAT markedly
      increased and the levels of MDA and 8-iso-PGF2alpha markedly decreased in sera
      and hippocampus; the time in new zone and the percentage of freezing time
      dramatically increased at days 3 to 14 post-operations in sepsis+H2 group (P <
      0.05). CONCLUSION: H2 inhalation can significantly alleviate neuronal damage and
      improve cognitive dysfunction in CLP-induced SAE mice. And it is probably
      associated with the increased activities of antioxidant enzymes and the reduced
      levels of oxidative products.

PMID- 25573318
TI  - [Intracerelar ventricular injection of the antisense oligonucleotides of ERK5
      inhibits neuropathic pain].
AB  - OBJECTIVE: To explore the effects of extracellular signal-regulated protein
      kinase 5 signaling pathway in chronic constriction injury (CCI)-induced
      neuropathic pain above spinal cord level. METHODS: The CCI model of neuropathic
      pain was established. Intracerebroventricular injection of antisense
      oligonucleotides and immunohistochemical labeling technique were employed. And
      the heat and mechanical hyperalgesia responses were used to examine the affect of
      ERK5 in CCI-induced neuropathic pain and the expression of p-CREB (cAMP response
      element binding protein) in spinal cord. RESULTS: The mechanical paw withdrawal
      reflex threshold and thermal reflex latency became significantly lower in CCI
      induced mice. Compared with saline group, mechanical and thermal hyperalgesia
      significantly decreased and the expression of p-CREB protein decreased at spinal
      cord in oligonucleotide group. CONCLUSION: The ERK5 spinal cord neurons are
      involved in the regulation of CCI-induced neuropathic pain in mice. And this
      effect is achieved by adjusting the CREB-dependent gene expression.

PMID- 25573319
TI  - The immune response to short-duration exercise in trained, eumenorrhoeic women.
AB  - Few studies have characterised the immune response to exercise of different
      intensities and durations in women. In those that have, baseline hormone levels
      and training status were not always adequately controlled for. Here, leucocyte
      and cytokine profiles of 11 aerobically trained, eumenorrhoeic females (33 +/- 5
      years) in the early follicular phase of the menstrual cycle were characterised
      after 30-min exercise at 3 intensities: 90% lactate threshold (LT), LT, and 110%
      LT. Proposed cytokine response mediators were quantified: plasma lactate and
      basal oestradiol concentrations. Intensity-dependent increases occurred in total
      white blood cells and lymphocyte counts (P < 0.001). Elevated plasma IL-6 and IL
      1ra concentrations post-exercise [F = 12.38, P < 0.01 and F = 7.65, P < 0.05,
      respectively] were not intensity-dependent, indicating that cytokine release may
      be better associated with exercise duration than intensity in trained women.
      Changes in plasma IL-1ra and basal oestradiol (rho = -0.893, P < 0.01) were
      correlated at intensities above LT only. These findings suggest a role for plasma
      sex hormones in moderating the exercise-induced immune response in women.
      However, the associations observed did not account for the magnitude of the
      cytokine response observed, and future studies should explore contributions of
      other potential mediators following short-duration exercise.

PMID- 25573321
TI  - Bone marrow stem cells: current and emerging concepts.
AB  - The interactions of stromal cells with hematopoietic cells in the bone marrow
      have long been a subject of research, but only recently have technologies allowed
      us to dissect them at the stem cell level. On the other hand, limitations of
      these technical tools might explain numerous discrepancies in this field. It is
      becoming increasingly clear that mesenchymal stem cells (MSCs) represent an
      important component of the hematopoietic stem cell (HSC) niche in the bone
      marrow. However, there is heterogeneity among HSCs, and many putatively different
      mesenchymal progenitors identified in the bone marrow using Cre recombinase
      driven mouse lines seem to exhibit HSC niche properties. Development of better
      reporter lines has demonstrated that some of these Cre lines do not always
      specifically mark the expected cells. Also, characterization of different cell
      populations has often been partial, and issues of redundancy and compensation
      might explain apparently contradictory results. Recognizing and overcoming these
      limitations, while also clearly defining the distinctions between subgroups of
      mesenchymal cells, will be essential to advance the field. 

PMID- 25573320
TI  - Lower serum magnesium is associated with cardiovascular risk factors and
      mortality in haemodialysis patients.
AB  - BACKGROUND: Hypomagnesaemia is a cardiovascular (CV) risk factor in the general
      population. The aim of this study was to evaluate the relationship between pre
      dialysis magnesium (Mg) and CV risk markers, [including pulse pressure (PP), left
      ventricular mass index (LVMI) and vascular calcifications (VC)], and mortality in
      haemodialysis (HD) patients. METHODS: We performed a 48-month prospective study
      in 206 patients under pre-dilution haemodiafiltration with a dialysate Mg
      concentration of 1 mmol/l. RESULTS: Lower Mg concentrations were predictors of an
      increased PP (>=65 mm Hg) (p = 0.002) and LVMI (>=140 g/m(2)) (p = 0.03) and of a
      higher VC score (>=3) (p = 0.01). Patients with Mg <1.15 mmol/l had a lower
      survival at the end of the study (p = 0.01). Serum Mg <1.15 mmol/l was an
      independent predictor of all-cause (p = 0.01) and CV mortality (p = 0.02) when
      adjusted for multiple CV risk factors. CONCLUSIONS: Lower Mg levels seem to be
      associated with increased CV risk markers, like PP, LVMI and VC, and with higher
      mortality in HD patients.

PMID- 25573322
TI  - CB1 cannabinoid receptors mediate endochondral skeletal growth attenuation by
      Delta9-tetrahydrocannabinol.
AB  - The endocannabinoid (EC) system regulates bone mass. Because cannabis use during
      pregnancy results in stature shorter than normal, we examined the role of the EC
      system in skeletal elongation. We show that CB1 and CB2 cannabinoid receptors are
      expressed specifically in hypertrophic chondrocytes of the epiphyseal growth
      cartilage (EGC), which drives vertebrate growth. These cells also express
      diacylglycerol lipases, critical biosynthetic enzymes of the main EC, and 2
      arachidonoylglycerol (2-AG), which is present at significant levels in the EGC.
      Femora of CB1- and/or CB2-deficient mice at the end of the rapid growth phase are
      longer compared to wild-type (WT) animals. We find that Delta(9) 
      tetrahydrocannabinol (THC) slows skeletal elongation of female WT and CB2-, but
      not CB1-, deficient mice, which is reflected in femoral and lumbar vertebral body
      length. This in turn results in lower body weight, but unaltered fat content. THC
      inhibits EGC chondrocyte hypertrophy in ex vivo cultures and reduces the
      hypertrophic cell zone thickness of CB1-, but not CB2-, deficient mice. These
      results demonstrate a local growth-restraining EC system in the EGC. The
      relevance of the present findings to humans remains to be studied. 

PMID- 25573324
TI  - Transcatheter removal of atrial septal stent placed to decompress left atrium
      with VA ECMO.
AB  - Left atrial (LA) decompression in infants with thick atrial septum placed on veno
      arterial extracorporeal membrane oxygenation (ECMO) can be reliably achieved with
      transcatheter atrial septal (AS) stent placement. However, with myocardial
      recovery and ECMO decannulation the stent causes a permanent left to right shunt
      and surgical removal of the AS stent is usually accomplished. Transcatheter
      removal of AS stent is an attractive option as the advantages of LA decompression
      would then be coupled with the advantage of avoiding a sternotomy for surgical
      removal of the stent. To our knowledge, this is the first reported case of
      successful transcatheter retrieval of AS stent used for LA decompression in a 13
      month-old child.

PMID- 25573325
TI  - Serum microRNA profiles in cats with hypertrophic cardiomyopathy.
AB  - The role of microRNAs (miRNAs) in the pathogenesis of heart diseases of humans
      and rodents, as well as their diagnostic potential, has recently received much
      attention, but comparable studies for spontaneous disease models in the domestic
      cat are missing. Hypertrophic cardiomyopathy (HCM) is the most common heart
      disease in cats. The pathology is largely unknown, but is suspected to be
      influenced by genetic background. In this study, we examined the miRNA profiles
      in the serum of cats with stable congestive heart failure caused by HCM (n = 11)
      and healthy control cats (n = 12) using miRNA arrays. 965 out of 2026 miRNAs
      could be detected in at least six samples of either of the groups. Eleven
      mammalian miRNAs were differentially expressed between the groups with a fold
      change >= 1.6. Hierarchical cluster analysis resulted in distinct separation of
      the two groups. After correction for multiple testing (adjusted p < 0.05), a
      higher expression of miR-381-3p, miR-486-3p, miR-4751, miR-476c-3p, miR-5700, miR
      513a-3p, and miR-320e in the HCM group was confirmed. Additionally, miR-1246 was
      found to be upregulated 3-fold in the HCM group using quantitative RT-PCR.
      Software analysis of the significantly regulated miRNAs revealed 49 mRNA targets
      involved in cardiac hypertrophy. Cats with primary HCM show a distinct miRNA
      profile that includes miRNAs that have already been shown to be differentially
      regulated in human patients and rodent models for cardiac disease. Studying HCM
      as a spontaneous cardiac disease of the cat may help to reveal additional
      pathophysiologic pathways. 

PMID- 25573327
TI  - Stroke prevention--medical and lifestyle measures.
AB  - BACKGROUND: According to the World Health Organization, stroke is the 'incoming
      epidemic of the 21st century'. In light of recent data suggesting that 85% of all
      strokes may be preventable, strategies for prevention are moving to the forefront
      in stroke management. SUMMARY: This review discusses the risk factors and
      provides evidence on the effective medical interventions and lifestyle
      modifications for optimal stroke prevention. Key Messages: Stroke risk can be
      substantially reduced using the medical measures that have been proven in many
      randomized trials, in combination with effective lifestyle modifications. The
      global modification of health and lifestyle is more beneficial than the treatment
      of individual risk factors. CLINICAL IMPLICATIONS: Hypertension is the most
      important modifiable risk factor for stroke. Efficacious reduction of blood
      pressure is essential for stroke prevention, even more so than the choice of
      antihypertensive drugs. Indications for the use of antihypertensive drugs depend
      on blood pressure values and vascular risk profile; thus, treatment should be
      initiated earlier in patients with diabetes mellitus or in those with a high
      vascular risk profile. Treatment of dyslipidemia with statins, anticoagulation
      therapy in atrial fibrillation, and carotid endarterectomy in symptomatic high
      grade carotid stenosis are also effective for stroke prevention. Lifestyle
      factors that have been proven to reduce stroke risk include reducing salt,
      eliminating smoking, performing regular physical activity, and maintaining a
      normal body weight.

PMID- 25573326
TI  - Spleen-specific isoforms of Pax5 and Ataxin-7 as potential proteomic markers of
      lymphoma-affected spleen.
AB  - The splenomegaly, enlargement of spleen, has been observed in several diseases.
      It has been intended to evaluate histochemical alterations, spleen-specific
      enzymatic and proteomic markers during splenomegaly, and lympho-proliferative
      disorders from spleen of mice bearing Dalton's lymphoma. The higher expression of
      c-fos, c-jun, and MAPK testifies proliferation of lymphocytes. The lower
      expression of Pax5, higher expression of CD3, and the presence of additional form
      of Zap-70 suggest hypertrophy of follicles and splenomegaly influenced by weak B
      cell receptor-mediated signaling, but activated T-cell receptor-mediated
      signaling. Simultaneously, lower levels of SOD, NDR2, and MIB2 and higher
      expression levels of Ataxin-7 and LDH also suggest impact of stress either as a
      cause or effect of cell proliferation. Spleen-specific isoform of Pax5, NDR2,
      MIB2, and Ataxin-7 can be considered as spleen-specific unique molecular markers
      for the evaluation of splenomegaly and lympho-proliferative disorders. 

PMID- 25573328
TI  - Clinical study of the caries-preventive effect of resin-modified glass ionomer
      restorations: aging versus the influence of fluoride dentifrice.
AB  - AIM: The use of fluoride-releasing materials could be compromised due to aging
      and might also be influenced by other ordinary sources of fluoride. The aim of
      the present study was to investigate the aging effect on caries development
      around resin-modified glass ionomer cement (RMGIC) restorations and the influence
      of fluoride dentifrice use in this process under the oral environment. METHODS: A
      clinical study was performed in two phases of 14 days each. A total of 16
      volunteers wore palatal devices containing dental slabs restored with either a
      composite resin or RMGIC, either aged or unaged by thermocycling. To simulate a
      clinical situation of high caries risk, the slabs were exposed to a 20% sucrose
      solution 10 times per day via the in situ model, where non-fluoride or a fluoride
      dentifrice was used. Integrated demineralization was determined by cross
      sectional microhardness at both margins of the restoration: enamel and dentin.
      RESULTS: For enamel, higher demineralization around the composite restorations
      was observed, regardless of dentifrice or aging. For dentin, higher
      demineralization was observed around the aged composite restorations regardless
      of the dentifrice type used. CONCLUSIONS: The RMGIC restorations provided more
      enhanced protection against secondary caries for dentin under aging, and the
      fluoride dentifrice used in this condition had either no clinically relevance or
      only a minimal effect.

PMID- 25573329
TI  - Ba3P5N10Br:Eu(2+): a natural-white-light single emitter with a zeolite structure
      type.
AB  - Illumination sources based on phosphor-converted light emitting diode (pcLED)
      technology are nowadays of great relevance. In particular, illumination-grade
      pcLEDs are attracting increasing attention. Regarding this, the application of a
      single warm-white-emitting phosphor could be of great advantage. Herein, we
      report the synthesis of a novel nitridophosphate zeolite Ba3P5N10Br:Eu(2+). Upon
      excitation by near-UV light, natural-white-light luminescence was detected. The
      synthesis of Ba3P5N10Br:Eu(2+) was carried out using the multianvil technique.
      The crystal structure of Ba3P5N10Br:Eu(2+) was solved and refined by single
      crystal X-ray diffraction analysis and confirmed by Rietveld refinement and FTIR
      spectroscopy. Furthermore, spectroscopic luminescence measurements were
      performed. Through the synthesis of Ba3P5N10Br:Eu(2+), we have shown the great
      potential of nitridophosphate zeolites to serve as high-performance luminescence
      materials.

PMID- 25573330
TI  - Production of a high level of laccase by submerged fermentation at 120-L scale of
      Cerrena unicolor C-139 grown on wheat bran.
AB  - Submerged fermentation in a stirred bioreactor of the white rot fungus Cerrena
      unicolor C-139 was done at a 120-L scale in the presence of wheat bran as a cheap
      lignocellulosic substrate for fungus growth and laccase production. Enzyme
      monitoring showed that laccase production started after 2 days of cultivation,
      attaining a maximum activity of 416.4 U.mL(-1) at day 12 of fermentation. After
      treatment of culture liquid by successive micro- and ultrafiltration (5kDa), a
      liquid concentrate containing 22203176 units of laccase was obtained. Obtaining
      large amount of laccase is essential for various industrial applications,
      including detoxification of industrial effluents, textile and petrochemical
      industries, polymer synthesis, bioremediation of contaminated area, stabilization
      of beverages, production of cosmetics, manufacture of anti-cancer drugs, and
      nanobiotechnology. The cultivation method and the fungal strain used here
      provided a substantial amount of enzyme produced at a price lower than 0.01 ?
      cent/unit enzyme.

PMID- 25573331
TI  - Acute leriche syndrome due to sarcoma of left atrium.

PMID- 25573332
TI  - SNPs selection using support vector regression and genetic algorithms in GWAS.
AB  - INTRODUCTION: This paper proposes a new methodology to simultaneously select the
      most relevant SNPs markers for the characterization of any measurable phenotype
      described by a continuous variable using Support Vector Regression with Pearson
      Universal kernel as fitness function of a binary genetic algorithm. The proposed
      methodology is multi-attribute towards considering several markers simultaneously
      to explain the phenotype and is based jointly on statistical tools, machine
      learning and computational intelligence. RESULTS: The suggested method has shown
      potential in the simulated database 1, with additive effects only, and real
      database. In this simulated database, with a total of 1,000 markers, and 7 with
      major effect on the phenotype and the other 993 SNPs representing the noise, the
      method identified 21 markers. Of this total, 5 are relevant SNPs between the 7
      but 16 are false positives. In real database, initially with 50,752 SNPs, we have
      reduced to 3,073 markers, increasing the accuracy of the model. In the simulated
      database 2, with additive effects and interactions (epistasis), the proposed
      method matched to the methodology most commonly used in GWAS. CONCLUSIONS: The
      method suggested in this paper demonstrates the effectiveness in explaining the
      real phenotype (PTA for milk), because with the application of the wrapper based
      on genetic algorithm and Support Vector Regression with Pearson Universal, many
      redundant markers were eliminated, increasing the prediction and accuracy of the
      model on the real database without quality control filters. The PUK demonstrated
      that it can replicate the performance of linear and RBF kernels.

PMID- 25573333
TI  - Adoptive transfer of allogeneic regulatory T cells into patients with chronic
      graft-versus-host disease.
AB  - BACKGROUND AIMS: Mouse models indicate that adoptive transfer of regulatory T
      cells (Treg) may suppress graft-versus-host-disease (GvHD) while preserving graft
      versus-leukemia reactions. We aimed to develop a protocol for the efficient
      isolation and in vitro expansion of donor-derived Treg and to establish the proof
      of-concept for the clinical application of ex vivo-generated Treg preparations in
      five patients with otherwise treatment-refractory chronic GvHD (cGvHD). METHODS:
      Allogeneic Treg were isolated from unstimulated leukapheresis products of the
      corresponding human leukocyte antigen-matched donors by use of clinical-grade
      magnetic-activated bead sorting. To increase the amount and purity, Treg were
      cultivated for 7-12 days and infused after a median time of 35 months after
      allogeneic hematopoietic cell transplantation. RESULTS: Final products contained
      Treg with a median purity of 84.1% CD4(+)CD25(high)CD127(low)FOXP3(+)of CD45(+)
      cells and a mean quantity of 2.4 * 10(6) Treg per kg body wt. All isolated cell
      products showed in vitro suppressive activity. On transfusion, two of five
      patients showed a clinical response with improvement of cGvHD symptoms. The other
      three patients showed stable cGvHD symptoms for up to 21 months. In four of five
      patients, increased counts of Treg were detectable on Treg transfusion,
      immunosuppressive treatment could be reduced and suppression of CD69 activation
      marker expression on T-effector cells was observed. However, one patient had
      development of malignant melanoma and another patient had Bowen skin cancer 4
      months and 11 months after Treg transfusion, respectively. CONCLUSIONS: We
      demonstrate a feasible and reproducible approach of isolating functional Treg in
      high quantity and purity for clinical application and show opportunities and
      risks of adoptive Treg transfer into patients with cGvHD.

PMID- 25573334
TI  - Different cytokine and stimulation conditions influence the expansion and immune
      phenotype of third-generation chimeric antigen receptor T cells specific for
      tumor antigen GD2.
AB  - BACKGROUND AIMS: Chimeric antigen receptor (CAR) T cells are a novel
      immunotherapy for cancer. To achieve anti-tumor efficacy, these cells must
      survive, expand, and persist after infusion into patients, functions that are
      reportedly best achieved by cells with a stem or central-memory rather than
      effector-memory phenotype. We have developed third-generation CAR T cells
      specific for the tumor-associated antigen GD2 for use in a phase I clinical
      trial. We investigated the optimal cell culture conditions for CAR T-cell
      production, and here we describe the relative effects of 3 activation and
      cytokine conditions on CAR T-cell expansion, effector function and phenotype.
      METHODS: Peripheral blood mononuclear cells were activated by anti-CD3 and anti
      CD28 or anti-CD3 and Retronectin. Activated cells were transduced with the CAR
      encoding retroviral vector and expanded in either interleukin (IL)-2 or IL-7 and
      IL-15. Immune phenotype and expansion were tracked throughout the culture, and
      transduction efficiency, and subsequent GD2-specific effector functions were
      evaluated by flow cytometry and cytotoxic T lymphocytes assay. RESULTS:
      CD3/Retronectin stimulation with IL-2 resulted in poorer activation, expansion
      and Th1 cytokine secretion of CAR T cells than CD3/CD28 stimulation with either
      IL-2 or IL-7 and IL-15. However, CAR T cells cultured in CD3/CD28/IL7/IL-15 and
      CD3/Retronectin/IL-2 had superior cytotoxic T lymphocyte activity and a more stem
      like phenotype. DISCUSSION: The combination of CD3 and CD28 with IL-7 and IL-15
      gave the best balance of CAR T-cell expansion and potent GD2-specific effector
      functions while retaining a stem/memory phenotype, and these growth conditions
      will therefore be used to manufacture CAR T cells for our phase I clinical trial.

PMID- 25573335
TI  - No abnormalities of intrinsic brain connectivity in the interictal phase of
      migraine with aura.
AB  - BACKGROUND AND PURPOSE: Functional neuroimaging studies have shown
      hyperresponsiveness of cortical areas to visual stimuli in migraine patients with
      aura outside of attacks. This may be a key feature in the initiation of aura
      episodes and possibly also migraine headache attacks. It is unknown if cortical
      dysfunction is present at rest, i.e. in the absence of any external stimuli.
      Functional magnetic resonance imaging is a powerful technique for evaluating
      resting state functional connectivity, i.e. coherence of brain activity across
      cerebral areas. The objective of this study was to investigate resting-state
      functional brain connectivity in migraineurs with aura outside of attacks using
      functional magnetic resonance imaging. METHODS: Forty patients suffering from
      migraine with visual aura and 40 individually age and gender matched healthy
      controls with no history or family history of migraine were investigated.
      Following advanced denoising, the data were analyzed both in a hypothesis-driven
      fashion, testing for abnormalities involving 27 different brain areas of
      potential relevance to migraine with aura including the cortical visual areas,
      the amygdala and peri-aqueductal grey matter, and in a data-driven exploratory
      fashion (dual regression) in order to reveal any possible between-group
      differences of resting state networks. Age, gender, attack frequency and disease
      duration were included as nuisance variables. RESULTS: No differences of
      functional connectivity were found between patients and controls. CONCLUSIONS:
      The previously reported increased cortical hyperresponsivity in the interictal
      phase of migraine with aura is unlikely to be caused by abnormalities of
      intrinsic brain connectivity. The interictal migraine aura brain may be
      abnormally functioning only during exposure to external stimuli.

PMID- 25573336
TI  - Unbalanced translocations involving chromosome region 10q25.3q26.3 in patients
      with intellectual disability and complex phenotypes.
AB  - We describe 2 Ukrainian families with unbalanced reciprocal translocations (RTs)
      involving the distal part of chromosome 10q. In both families, the fathers were
      healthy carriers of the RT. Two affected patients from the first family had an
      ~2.3-Mb loss at 10q26.3 and an ~25-Mb gain at 2q35qter, and the patient from the
      other family had an ~12.5-Mb loss at 5p15.2pter and an ~18-Mb gain at
      10q25.3q26.3. We assume that intellectual disability (ID) in association with
      congenital anomalies observed in our patients was the result of the cumulative
      effect of both gains and losses of the chromosomal regions involved in each
      translocation. Comparison of the sizes of the deleted and duplicated segments in
      our families as well as in other published families with translocations affecting
      the distal part of 10q showed that generally deletions seem to be ~2 times more
      harmful than duplications of the same size. The data obtained here may contribute
      to improve the diagnosis and genetic counseling of families with similar
      chromosomal imbalances.

PMID- 25573337
TI  - Geminal dihalogen isosteric replacement in hydrated AI-2 affords potent quorum
      sensing modulators.
AB  - Hydrated carbonyl groups in AI-2, a quorum sensing autoinducer, make key hydrogen
      bonding interactions in the binding site of LsrR (a transcriptional regulator).
      This can be recapitulated with geminal dibromides, via halogen bonding. Geminal
      dihalogens represent interesting isosteric replacements for hydrated carbonyls in
      ligands and are currently under-utilized in ligand design. 

PMID- 25573339
TI  - Estonia.

PMID- 25573340
TI  - Limb-girdle weakness in a marfanoid man: distinguishing calpainopathy from
      Becker's muscular dystrophy.

PMID- 25573341
TI  - Serum CK as a guide to the diagnosis of muscle disease.

PMID- 25573338
TI  - Chronic alcohol exposure exacerbates inflammation and triggers pancreatic acinar
      to-ductal metaplasia through PI3K/Akt/IKK.
AB  - Pancreatic acinar-to-ductal metaplasia (ADM) has been identified as an initiating
      event that can progress to pancreatic intraepithelial neoplasia (PanIN) or
      pancreatic ductal adenocarcinoma (PDAC). Acini transdifferentiation can be
      induced by persistent inflammation. Notably, compelling evidence has emerged that
      chronic alcohol exposure may trigger an inflammatory response of
      macrophages/monocytes stimulated by endotoxins. In the present study, we aimed to
      evaluate the role of inflammation induced by chronic alcohol and
      lipopolysaccharide (LPS) exposure in the progression of pancreatic ADM, as well
      as to elucidate the possible mechanisms involved. For this purpose, cultured
      macrophages were exposed to varying doses of alcohol for 1 week prior to
      stimulation with LPS. Tumor necrosis factor-alpha (TNF-alpha) and regulated upon
      activation, normal T cell expression and secreted (RANTES) expression were
      upregulated in the intoxicated macrophages with activated nuclear factor-kappaB
      (NF-kappaB). Following treatment with the supernatant of intoxicated macrophages,
      ADM of primary acinar cells was induced. Furthermore, the expression of TNF-alpha
      and RANTES, as well as the phosphatidylinositol-3-kinase (PI3K)/protein kinase
      B(Akt)/inhibitory kappaB kinase (IKK) signaling pathway have been proven to be
      involved in the ADM of acinar cells. Moreover, Sprague-Dawley (SD) rats were
      employed to further explore the induction of pancreatic ADM by chronic alcohol
      and LPS exposure in vivo. At the end of the treatment period, a number of
      physiological parameters, such as body weight, liver weight and pancreatic weight
      were reduced in the exposed rats. Plasma alcohol concentrations and oxidative
      stress levels in the serum, as well as TNF-alpha and RANTES expression in
      monocytes were also induced following chronic alcohol and LPS exposure. In
      addition, pancreatic ADM was induced through the PI3K/Akt/IKK signaling pathway
      by the augmented TNF-alpha and RANTES expression levels in the exposed rats.
      Overall, we characterized the link between inflammation induced by chronic
      alcohol and LPS exposure and pancreatic ADM. However, the mechanisms behind the
      induction of pancreatic ADM warrant further investigation.

PMID- 25573342
TI  - Reversible cerebral vasoconstriction syndrome: a rare cause of postpartum
      headache.
AB  - We describe two women presenting with severe postpartum headache associated with
      hypertension but with no other signs or investigation results to suggest pre
      eclampsia. In one case, the headache was associated with atypical subarachnoid
      haemorrhage. The variable nature of the headache and the degree of associated
      hypertension raised the clinical suspicion of reversible cerebral
      vasoconstriction syndrome, confirmed on MR angiography. Both patients took
      nimodipine until the cerebral vasoconstriction had resolved radiologically. 

PMID- 25573343
TI  - A practical approach to enlargement of nerves, plexuses and roots.
AB  - Detecting enlargement of accessible nerves is very helpful in assessing patients
      with peripheral nerve disorders, as only a few types of neuropathy lead to nerve
      thickening. The three leading causes are leprosy, hereditary motor and sensory
      neuropathies (types 1 and 3) and chronic inflammatory demyelinating neuropathies.
      MRI, neurography and ultrasonography allow assessment of clinically inaccessible
      portions of deep-seated nerves, plexuses and roots. As a result, isolated
      proximal segment thickenings, as found in chronic inflammatory sensory
      polyradiculopathy, can now be better evaluated and managed. Similarly, focal
      nerve enlargements due to infection, inflammation, infiltration and neoplasm are
      being identified and treated effectively. We present a practical approach to the
      diagnosis and management of patients with enlarged peripheral nerves, plexuses
      and roots, including cranial nerves. 

PMID- 25573344
TI  - Successful intermittent intravenous calcium treatment via the peripheral route in
      a patient with hereditary vitamin D-resistant rickets and alopecia.
AB  - BACKGROUND: Hereditary vitamin D-resistant rickets (HVDRR) is a rare genetic
      disorder caused by mutations in the vitamin D receptor (VDR) gene, which result
      in end-organ resistance to 1,25-(OH)2D3. PATIENTs with HVDRR are mostly treated
      using i.v. calcium therapy with a central catheter. However, central catheter
      related complications have been reported. PATIENT: The patient was a 3-year-old
      boy presenting with waddling gait and alopecia. He had hypocalcemia [8 mg/dl (2
      mmol/l)], hyperparathyroidism (1,232 ng/l), and elevated 1,25-(OH)2D3 levels
      (>250 pmol/l). DNA sequence analyses of the VDR gene showed a homozygous C-T
      transition at codon 152, resulting in a non-sense mutation in exon 5.
      INTERVENTIONS AND OUTCOMES: The patient was initially treated with calcitriol (80
      ng/kg/day) and high-dose oral calcium (150 mg/kg/day) for one year. At the end of
      the first year, intermittent (5 days per month) i.v. calcium therapy without a
      central catheter was initiated because of insufficient clinical and radiological
      improvement. After 2 years of intermittent i.v. calcium therapy, there was a
      clear improvement based on clinical progress and on X-ray and biochemical
      findings. No peripheral complications were reported either. CONCLUSION: HVDRR
      with a non-sense mutation in the ligand-binding domain and alopecia was
      successfully treated with intermittent i.v. calcium without a central catheter.

PMID- 25573345
TI  - Chimeric ubiquitin ligases inhibit non-small cell lung cancer via negative
      modulation of EGFR signaling.
AB  - Targeting epidermal growth factor receptor (EGFR) represents a promising
      therapeutic strategy for non-small cell lung cancers (NSCLC). The ubiquitin
      proteasome system (UPS) is a major pathway that mediates protein degradation. To
      target the degradation of EGFR, we generated two artificial ubiquitin ligases,
      which are composed of an EGFR-binding domain, i.e., the SH2 domain from growth
      factor receptor binding protein 2 (Grb2), and an ubiquitin ligase catalytic
      domain, i.e., the RING domain from Cbl or the U-box domain from CHIP. When the
      chimeric ubiquitin ligases were introduced into lung cancer SPC-A1 cells, they
      effectively associated with EGFR, promoted its ubiquitination and degradation,
      and as a result, blocked the downstream PI3K-Akt signal pathway. Moreover, cell
      proliferation and invasion were inhibited, the sensitivity to docetaxel-induced
      apoptosis was enhanced and the tumorigenicity was suppressed. In conclusion,
      negative modulation of EGFR signaling by the chimeric ubiquitin ligases can
      inhibit malignancy of SPC-A1 cells and sensitize these cells to chemotherapy,
      thus it may be applied to targeted therapy for NSCLC. 

PMID- 25573347
TI  - Effect of garlic powder tablet on carotid intima-media thickness in patients with
      coronary artery disease: a preliminary randomized controlled trial.
AB  - BACKGROUND/OBJECTIVES: This study was designed to investigate whether garlic
      powder tablets in adjunct to conventional medical treatment could have an effect
      on carotid intima-media thickness (CIMT) and plasma lipoproteins and lipids in
      patients with coronary artery disease (CAD). SUBJECTS/METHODS: A randomized,
      placebo-controlled, clinical trial was conducted on 56 patients with CAD between
      the ages of 25 and 75 years. The patients were randomly divided into two groups:
      garlic group (n = 27), receiving garlic powder tablet (1200 ug allicin/tab) twice
      daily and the placebo group (n = 29), receiving placebo for 3 months. The rate of
      atherosclerosis progression was measured by B-mode ultrasonography as the
      increase in CIMT. RESULTS: After 3 months of taking garlic tablets, CIMT values
      had minor variations (0.009 +/- 0.007 mm reduction from baseline), while in the
      placebo group, an increase in CIMT values was observed (0.04 +/- 0.01 mm increase
      from baseline). After 3 months of treatment, mean CIMT difference from baseline
      was significantly differ between the two groups (p < 0.001). Plasma lipids and
      lipoproteins (total cholesterol, triglycerides, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, Apolipoprotein A1 and
      Apolipoprotein B) did not differ between the two groups. CONCLUSIONS: The results
      suggest that dry garlic powder tablet is superior to placebo in prevention of
      CIMT progression in patients with CAD and may be considered as an adjunct
      treatment for atherosclerosis.

PMID- 25573348
TI  - Therapeutic vaccines in HBV: lessons from HCV.
AB  - Currently, millions of people infected with hepatitis B virus (HBV) are committed
      to decades of treatment with anti-viral therapy to control viral replication.
      However, new tools for immunotherapy that include both viral vectors and
      molecular checkpoint inhibitors are now available. This has led to a resurgence
      of interest in new strategies to develop immunotherapeutic strategies with the
      aim of inducing HBeAg seroconversion--an end-point that has been associated with
      a decrease in the rates of disease progression. Ultimately, a true cure will
      involve the elimination of covalently closed circular DNA which presents a
      greater challenge for immunotherapy. In this manuscript, I describe the
      development of immunotherapeutic strategies for HBV that are approaching or
      currently in clinical studies, and draw on observations of T cell function in
      natural infection supported by recent animal studies that may lead to additional
      rational vaccine strategies using checkpoint inhibitors. I also draw on our
      recent experience in developing potent vaccines for HCV prophylaxis based on
      simian adenoviral and MVA vectors used in prime-boost strategies in both healthy
      volunteers and HCV infected patients. I have shown that the induction of T cell
      immune responses is markedly attenuated when administered to people with
      persistent HCV viremia. These studies and recently published animal studies using
      the woodchuck model suggest that potent vaccines based on DNA or adenoviral
      vectored vaccination represent a rational way forward. However, combining these
      with drugs to suppress viral replication, alongside checkpoint inhibitors may be
      required to induce long-term immune control.

PMID- 25573346
TI  - Role of TGFbeta in regulation of the tumor microenvironment and drug delivery
      (review).
AB  - Deregulation of cell signaling homeostasis is a predominant feature of cancer
      initiation and progression. Transforming growth factor beta (TGFbeta) is a
      pleiotropic cytokine, which regulates numerous biological processes of various
      tissues in an autocrine and paracrine manner. Aberrant activity of TGFbeta
      signaling is well known to play dual roles in cancer, depending on tumor stage
      and cellular context. The crucial roles of TGFbeta in modulating the tumor
      microenvironment, its contribution to the accumulation of mechanical forces
      within the solid constituents of a tumor and its effects on the effective
      delivery of drugs are also becoming increasingly clear. In this review, we
      discuss the latest advances in the efforts to unravel the effects of TGFbeta
      signaling in various components of the tumor microenvironment and how these
      influence the generation of forces and the efficacy of drugs. We also report the
      implications of tumor mechanics in cancer therapy and the potential usage of anti
      TGFbeta agents to enhance drug delivery and augment existing therapeutic
      approaches. These findings provide new insights towards the significance of
      targeting TGFbeta pathway to enhance personalized tumor treatment.

PMID- 25573349
TI  - Impact of multiplex PCR on antimicrobial treatment in febrile neutropenia: a
      randomized controlled study.
AB  - Multiplex PCR (mPCR) directly from blood has been suggested as a promising method
      for rapid identification of pathogens causing sepsis. This study aimed to
      investigate whether mPCR has any impact on antimicrobial treatment. Hematological
      patients with febrile neutropenia were randomized into two groups. In the study
      group, mPCR was performed as an addition to standard diagnostics, and PCR finding
      was immediately communicated to the clinicians, thus being available for decision
      making. In the control group, clinicians were not aware of PCR result. PCR
      samples were collected simultaneously with clinically indicated blood culture
      specimens from peripheral vein and/or central venous catheter at fever onset and
      once again if fever persisted up to 72 h. Overall, 74 patients of the study group
      and 76 patients of the control group were enrolled and 253 samples collected.
      Therapy was changed to targeted antimicrobial therapy (AMT) in 12 patients
      (16.2%) in the study group and in 12 patients (15.8%) in the control group. For
      patients with changes, the median time to change to the targeted AMT was 21.4 h
      in the study group and 47.5 h in the control group (p = 0.018). In the study
      group, 57.1% (8/14) of changes to targeted AMT was due to PCR finding. PCR led to
      AMT change in 9.5% (7/74) of study group patients, i.e., in 33.3% (7/21) of
      patients who had positive PCR finding. There were no significant differences in
      patient outcomes (secondary endpoints). In conclusion, PCR method accelerates
      change to the targeted AMT in febrile neutropenic patients.

PMID- 25573350
TI  - Low Grade Serous Ovarian Carcinoma: from the molecular characterization to the
      best therapeutic strategy.
AB  - Low Grade Serous Ovarian Carcinoma, LGSOC, is certainly a rare disease,
      accounting for only a small proportion of all ovarian carcinomas, nevertheless in
      the last decade we have acquired many data about its molecular and clinical
      features and it has been largely accepted that it has distinct pathogenesis,
      genetic aberrations and clinical behavior compared to High Grade Serous Ovarian
      Carcinoma, HGSOC, which is the most common ovarian cancer histotype. A large
      number of series pointed out the high rate of KRAS and BRAF mutations in LGSOCs
      and Serous Borderline Tumors, SBLTs, in contrast with their rarity in HGSOC. Such
      finding, together with the recurrent observation of focus of LGSOC associated
      with areas of SBLT in the same lesion, led to abandon the traditional histology
      classification, defining three types of serous carcinomas, in favor of a new
      dualistic grading system which recognizes only LG and HG carcinomas corresponding
      to distinct tumorigenesis pathways, the former based on KRAS/BRAF mutations and
      alteration of the MAP/ERK signaling, the latter characterized by early genetic
      instability and wild type status of KRAS and BRAF. LGSOC shows favorable overall
      survival, compared to general ovarian cancer population, but worrying resistance
      to conventional treatments. MEK inhibitors are emerging as active agents and may
      well represent an effective therapeutic strategy in the near future. 

PMID- 25573352
TI  - Calcium ions facilitate body heat emission response to warming.
AB  - Involvement of various areas of the body surface in heat emission response to
      warming is characterized by a certain succession. The first response preceding
      the deep body temperature rise is dilation of ear skin vessels. Then, an increase
      in deep body temperature is counterbalanced by vascular reaction in the tail
      region, which plays the leading role in up-regulation of heat emission. Calcium
      ions accelerate the vascular response to warming in both regions, although they
      produce no effect on the maximum level of heat emission. Our findings confirm the
      involvement of Ca(2+)-dependent mechanisms in activation of the processes aimed
      at stabilization of body temperature in warm-blooded animals. The role of heat
      sensitive TRPV1 ion channels determining modality of the temperature signal and
      direction of effector reactions is discussed. 

PMID- 25573353
TI  - Peripheral administration of a MU-opioid receptor agonist DAMGO suppresses the
      anxiolytic and stimulatory effects of caffeine.
AB  - We studied the possibility of modulation of the stimulatory and anxiolytic
      effects of caffeine by activation of MU-opioid receptors in the gastrointestinal
      tract. Caffeine in a dose of 10 mg/kg (but not in a dose of 100 mg/kg) had a
      strong anxiolytic and psychostimulant effect. This effect was manifested in a
      significant increase in the time spent in the open arms of the elevated plus
      maze, elevation of locomotor activity, and stimulation of metabolism.
      Administration of DAMGO to animals receiving caffeine in a dose of 10 mg/kg
      abolished the anxiolytic and psychostimulant effects of caffeine. By contrast,
      administration of DAMGO to rats receiving caffeine in a dose of 100 mg/kg had the
      anxiolytic effect. Activation of peripheral MU-opioid receptors is followed by
      the inhibition of the central MU-opioid system. We observed a decrease in the
      number of MU-opioid receptors in the midbrain and cerebral cortex and inhibition
      of beta-endorphin release from nerve ending of the cingulate cortex in rats.
      These changes are probably followed by activation of the adenosine system in the
      brain. Caffeine dose should be increased to achieve the effect. Therefore, the
      anxiolytic and stimulatory effects of caffeine in a dose of 10 mg/kg are
      abolished under these conditions. By contrast, the anxiolytic effect of caffeine
      in a dose of 100 mg/kg (not observed under normal conditions) develops after this
      treatment. 

PMID- 25573354
TI  - Role of cholesterol in the maintenance of endplate electrogenesis in rat
      diaphragm.
AB  - Methyl-beta-cyclodextrin (0.1 mM) reduced resting potential of muscle fibers and
      abolished local endplate membrane hyperpolarization in rat diaphragm. This effect
      was associated with selective reduction of electrogenic activity of alpha2
      isoform of Na,K-ATPase without changes in the level of intracellular
      acetylcholine. Experiments with cholesterol marker filipin showed that methyl
      beta-cyclodextrin in this dose induced cholesterol translocation from lipid rafts
      to liquid phase of the membrane without its release into extracellular space.
      This modification of lipid rafts by methyl-beta-cyclodextrin presumably impaired
      the mechanism maintaining electrogenesis in endplates mediated by modulation of
      Na,K-ATPase by non-quantum acetylcholine. Cholesterol can serve as a molecular
      component of this mechanism. 

PMID- 25573355
TI  - Inhibition of secretory activity of atrial myocytes in hypertensive rats after
      losartan treatment.
AB  - Male ISIAH rats with inherited stress-induced arterial hypertension (BP 174.0 +/-
      1.3 mm Hg) received antagonist of angiotensin II receptors losartan in a dose of
      10 mg/kg/day for 16 days. Ultrastructural study of the right atrium showed signs
      of dramatic and pronounced inhibition of synthesis of the natriuretic peptides
      (changes in the composition of secretory granules and decrease in their
      population density and size) the atrial myocytes against the background of
      persistent BP decrease in hypertensive rats to 142.0 +/- 4.2 mm Hg. We concluded
      that myoendocrine cells in rats with stable hypertension retain ability to
      respond adequately to distention of the atria with blood.

PMID- 25573356
TI  - Correlation and spectral analysis of vascular tone regulator mechanisms in paired
      formations during postnatal ontogenesis in rats.
AB  - The study focused on the changes of microcirculation indices and components of
      the vascular tone of endothelial, neural, and myogenic nature in symmetrical skin
      sites of temples, forehead, auricles, scapulae, and groin during postnatal
      ontogeny. Initially, microcirculation indices in the symmetrical regions
      decreased to postnatal day 10, thereafter they surpassed the initial level at the
      age of 30 days. The endothelial, neural, and myogenic indices of vascular tone
      changed differently in the symmetrical left and right sites. On the right side,
      all indices increased by the postnatal day 21 ("redundancy" phase), and by
      postnatal day 30 surpassed the initial level by two times. On the left side, the
      redundancy phase manifested in the endothelial component on postnatal day 10, but
      to postnatal day 30 all three indices dropped below the initial level. 

PMID- 25573357
TI  - Effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the
      expression of Bax and Bcl-2 proteins in left-ventricular cardiomyocytes of
      spontaneously hypertensive rats.
AB  - We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate
      on the expression of Bax and Bcl-2 proteins in left-ventricular cardiomyocytes of
      spontaneously hypertensive rats (SHR). Both drugs have no effect on the
      expression of Bcl-2, but significantly reduce the level of Bax protein
      (phosphocreatine produces more pronounced effect). These data attest to an
      important role of energy deficit and oxidative stress in the induction of
      cardiomyocyte apoptosis in genetically determined arterial hypertension. 

PMID- 25573358
TI  - Increase of the seizure threshold in C57BL/6 mice after citicoline
      administration.
AB  - We studied the dose-dependent effect of preventive intraperitoneal injection of
      citicoline (cytidine 5'-diphosphocholine) on acute generalized epileptiform
      activity in C57Bl/6 mice. The duration of citicoline action was also evaluated.
      Administration of citicoline in doses of 500 and 1000 mg/kg 1 h before treatment
      with the convulsant agent pentylenetetrazole produced an anticonvulsant effect.
      This effect was manifested in an increase of the threshold of clonic seizures and
      tonic phase of seizures with lethal outcome. Moreover, the latency of seizure
      development was elevated under these conditions. The anticonvulsant effect of
      citicoline persisted for 6 h after its injection. 

PMID- 25573359
TI  - Neuroprotective and antiamnesic effect of erythropoietin derivatives after
      experimental ischemic injury of cerebral cortex.
AB  - Using the model of bilateral photothrombosis of the blood vessels in the
      prefrontal cortex we have shown that new hybrid proteins derived from recombinant
      human erythropoietin, carbamylated EPO-Fc and EPO-TR fusion proteins, injected
      intraperitoneally 1 h after ischemic injury contribute to restoration of passive
      avoidance response formed before photothrombotic injury and reduction in the
      volume of the ischemic focus. These data attest to nootropic and neuroprotective
      activities of these hybrid proteins. Carbamylated glycopeptide derivative EPO-TR
      exhibited prolonged neuroprotective properties.

PMID- 25573361
TI  - Ca2+ ions regulate activity of Na+ ,Cl-(HCO3 -)-ATPase in the mucosa of rabbit
      small intestine.
AB  - We studied the effects of bivalent metal ions on activity of Na(+),Cl(-)(HCO3 (
      ))-ATPase was studied. In contrast to Ba(2+), Co(2+), Zn(2+), and Mn(2+) ions,
      Ca(2+) and Mg(2+) ions in a concentration of 0.25 mM completely inhibited this
      enzyme. Histamine in vivo significantly decreased the inhibiting effect of Ca(2+)
      on Na(+),Cl(-)(HCO3 (-))-ATPase. A possible mechanism of regulation of enzyme
      activity by Ca(2+) ions and its possible relation with CFTR protein providing
      permeability of enterocyte apical membrane for Cl(-) ions was proposed. 

PMID- 25573360
TI  - Serum, liver, and lung levels of the major extracellular matrix components at the
      early stage of BCG-induced granulomatosis depending on the infection route.
AB  - Experiments on the model of mouse BCG-induced granulomatous showed that the
      content of glycosaminoglycans and proteoglycans in the extracellular matrix of
      the liver and lungs are changed at the early stages of inflammation (days 3 and
      30 postinfection) before cell destruction in the organs begins. This is related
      to degradation of extracellular matrix structures. Their high content in the
      blood and interstitium probably contributes to the formation of granulomas,
      fibroblast proliferation and organ fibrosis. These processes depend on the
      infection route that determines different conditions for generalization of the
      inflammation process. Intravenous method of vaccine injection is preferable to
      use when designing the experiments simulating tuberculosis granulomatosis,
      especially for the analysis of its early stages. 

PMID- 25573362
TI  - Biochemical features in rats with different behavioral activity under conditions
      of emotional stress.
AB  - Adaptive capacities of the organism under conditions of emotional stress are
      determined by individual complex of anti-stress protective mechanisms. We studied
      the content of coenzyme Q10 and the spectrum of polyunsaturated fatty acids omega
      3 and omega-6 in the serum, liver, and brain, and LPO intensity in the serum and
      liver of behaviorally active and passive rats under conditions of acute emotional
      stress. The differences in the formation of adaptive responses in animals with
      various behavioral activities were demonstrated. 

PMID- 25573363
TI  - Mdm2-dependent regulation of p53 expression during long-term potentiation.
AB  - Induction of long-term posttetanic potentiation in rat hippocampal CA1 filed was
      followed by a decrease in the content of transcription factor p53 against the
      background of unchanged level of p53 mRNA, which implies activation of negative
      regulators of p53. Mdm2 is an important regulator of p53. We studied the effects
      of Mdm2 inhibitor nutlin-3 on p53 expression during generation of long-term
      posttetanic potentiation. Mdm2 inhibition completely prevented tetanization
      induced decrease in the content of p53 protein; the level of p53 mRNA tended to
      increase in 30 min after tetanization. Thus, Mdm2 contributes to the maintenance
      of constant level of mRNA and plays a pivotal role in the decrease in the level
      of p53 protein during induction of long-term potentiation. 

PMID- 25573364
TI  - Hepatoprotective properties of betulonic acid amide and heptral in toxic liver
      injury induced by carbon tetrachloride in combination with ethanol.
AB  - Toxic liver injury with the development of fibrosis and cirrhosis was modeled in
      Wistar rats by intragastric administration of 0.1 ml/kg CCl4 in combination with
      5% ethanol with glucose 3 times a week for 6 weeks. The animals were treated with
      betulonic acid amide (50 mg/kg in Tween aqueous solution) and heptral (6 mg/kg)
      as hepatoprotective compounds. It was found that betulonic acid amide stimulated
      the regenerative response in hepatocytes under conditions of combined toxic
      exposure and promoted recovery of their qualitative and quantitative
      characteristics, which was accompanied by a significant decrease in the severity
      of liver fibrosis and the absence of cirrhotic transformation of the liver.

PMID- 25573365
TI  - Efficacy of green tea extract in two exercise models.
AB  - Oral administration of green tea extract in a dose of 6 mg/kg twice a day (before
      and after exercise) over 2 weeks significantly increased swimming times on week 1
      and 2 in comparison with control animals receiving water. The 7-day and final
      exhaustive running in rats was accompanied by a significant decrease in spleen
      weight and iron serum levels associated with developed reticulocytosis.
      Administration of green tea extract in a dose of 12 mg/kg once a day (before
      exercise) for 2 weeks did not affect the duration of the running, but prevented
      the decrease in serum iron and spleen weight, that, along with a significantly
      increased concentration of reduced glutathione in erythrocytes, can indicate a
      normalizing effect of green tea extract on hemopoiesis and stimulating effect on
      the antioxidant system of erythrocytes. 

PMID- 25573366
TI  - Effects of hydroxypyridine derivatives mexidol and emoxypin on the reparative
      processes in rabbit eye on the models of corneal epithelial defect and
      conjunctival ischemia.
AB  - Deepithelialization of the cornea (diameter 7 mm) was performed in rabbits and
      the rate of defect epithelialization was evaluated. Conjunctival ischemia was
      modeled by application of graduated alkaline burn. Antioxidant activity and
      content of nitrates and nitrites was measured in the tear fluid before and after
      burn by chemiluminescence and Griess methods, respectively. Emoxypin and mexidol
      promoted healing of corneal epithelial defect at the stage of epitheliocyte
      migration to the defect area and at the stage of their proliferation,
      respectively. After treatment with both agents, the area of conjunctival ischemia
      decreased more rapidly, but the efficiency of mexidol was higher. Antioxidant
      activity and content of products of NO metabolism in tear fluid decreased after
      burn. Mexidol, but not emoxypin, increased these parameters. Thus, mexidol and
      emoxypin have different effects on corneal epithelialization and conjunctival
      ischemia and effects of mexidol are more pronounced.

PMID- 25573367
TI  - Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the
      hippocampus.
AB  - Application of nootropic agent Noopept on hippocampal slices from Wistar rats
      enhanced the inhibitory component of total current induced by stimulation of
      Shaffer collaterals in CA1 pyramidal neurons, but did not affect the excitatory
      component. A direct correlation between the increase in the amplitude of
      inhibitory current and agent concentration was found. The substance did not
      affect the release of inhibitory transmitters from terminals in the pyramidal
      neurons, which indicated changes in GABAergic interneurons. 

PMID- 25573368
TI  - Cerebroprotective and regenerative effects of alkaloid Z77 under conditions of
      brain ischemia.
AB  - We studied the psychopharmacological effects of atisine-type diterpene alkaloid
      Z77 in a rat model of cerebral ischemia. Pronounced cerebroprotective effect was
      found consisting in normalization of the orienting and exploratory activity and
      conditioned behavior associated with significant correction of morphological
      changes in the brain. The direct stimulatory effect of Z77 on neural stem cells
      was shown in vitro.

PMID- 25573369
TI  - Effects of beta-endorphin on functional activity of mouse splenocytes under
      conditions of in vivo blockade of MU,delta-opioid receptors.
AB  - Blockade of delta-receptors with naltrindole under conditions of systemic
      immunization abolished the stimulatory effect of beta-endorphin (0.0005 MUg/kg)
      on the counts of antibody-producing cells and the titer of antierythrocyte
      antibodies. Injection of beta-endorphin to mice led to stimulation of
      concanavalin A-induced proliferative activity of splenocytes and IL-4 secretion
      by the naloxone-dependent mechanism. The peptide did not modify the production of
      IL-2 and IFN-gamma.

PMID- 25573370
TI  - Effects of allogenic fetal pancreatic tissue transplantation on regeneration of
      islet cells in recipient rats with alloxan-induced diabetes mellitus.
AB  - The linear parameters and number of Langerhans islets were evaluated in rats with
      alloxaninduced diabetes mellitus after transplantation of fetal pancreatic tissue
      to the anterior chamber of the eye. The islets significantly increased in size by
      week 3 after surgery and a trend to an increase in their number was observed. 

PMID- 25573371
TI  - Site-directed delivery of VEGF-targeted liposomes into intracranial C6 glioma.
AB  - The efficiency of conventional chemotherapy for aggressive tumors in the CNS
      remains low and new strategies for the targeted delivery of anti-tumor substances
      are now actively developed. Pegylated liposomes covalently conjugated with
      monoclonal antibodies to VEGF synthesized by us are nanoparticle characterized by
      narrow size distribution and high dispersion stability. Immunochemical activity
      of antibodies after conjugation was 70% of initial level. The anti-VEGF liposomes
      developed by us were highly specific for VEGF(+) tumor cells (in vitro and in
      vivo). Intravenous injection of VEGF-liposomes to rats with intracranial C6
      glioma was followed by their specific accumulation in the malignant tissues and
      engulfment by glioma cells, which attested to target delivery and selective
      accumulation of anti-VEGF-liposomes in the brain tumor. Thus, the use of
      targeting molecules can significantly increase the distribution and efficiency of
      delivery of nanocontainers to a tumor characterized by hyperexpression of the
      target proteins. 

PMID- 25573373
TI  - Infradian biorhythms of mitotic activity esophageal epithelium in male Wistar
      rats.
AB  - Infradian rhythms of esophageal epithelium mitotic activity were studied in male
      Wistar rats of two age groups: 35-45 days (prepubertal) and 3-4 months (adults).
      Studies of the time course of esophageal epithelium mitotic indexes in adult
      males showed 4- and 12-day biorhythms, while prepubertal rats exhibited only 4
      day infradian biorhythms of this parameter. Studies of the mitotic activity over
      long periods (3 years) showed 4.058- and 12.175-day periodicity of infradian
      biorhythms for this parameter, presumably due to external exposures synchronizing
      the biorhythms. Studies of the mean daily values of the Bz component of
      interplanetary magnetic field during the period of our research (2012-2013)
      showed rhythmicities analogous to changes in the mitotic activity of the
      epithelium. The minimum mitotic indexes were detected on the days of the most
      pronounced negative values of the interplanetary magnetic field Bz component. 

PMID- 25573372
TI  - Role of heat shock protein 27 in regulation of glutathione system and apoptosis
      of Jurkat tumor cells and blood lymphocytes.
AB  - Reaction of the glutathione system of Jurkat tumor cells and blood lymphocytes
      was evaluated under conditions of culturing with 5-(5-ethyl-2-hydroxy-4
      methoxyphenyl)-4-(4-methoxyphenyl) isoxazole (KRIBB3), a selective inhibitor of
      heat shock protein Hsp27. The results indicated the regulatory role of Hsp27 in
      the maintenance of the functional activities of glutathione reductase,
      glutathione peroxidase, and realization of apoptotic death of Jurkat cells and
      blood lymphocytes. Inhibition of Hsp27 in Jurkat tumor cells led to imbalance of
      the glutathione system and increase of the share of annexin-positive cells.

PMID- 25573374
TI  - Structural organization of glial cells at the border between the neurotransplant
      and recipient brain.
AB  - Integration of fetal hippocampal dentate fascia neurotransplants with the
      neocortical somatosensory region in adult rats was studied by electron
      microscopy. The growth of nerve fiber through the neurotransplant/brain border
      formed by the glial cells was studied. The interface zone was organized by
      various astrocyte subpopulations and ependymocytes forming multilamellar
      accumulations in some sites of the interface. These conglomerations of the glial
      cells and their processes did not prevent the growth of axonal and axodendritic
      bundles; moreover, fibrous astrocyte axons accompanied them. Under conditions of
      immature nervous tissue transplantation to the focus of mature brain damage, the
      glial cells created a substrate in the interface permeable for nerve fibers, thus
      promoting the functional integration of the neurotransplant. 

PMID- 25573375
TI  - Method for determining the level of food motivation in rats.
AB  - A new method for the quantitative evaluation of the level of food motivation was
      developed. This method takes into account not only the information, but also the
      energy component of operant feeding behavior of different intensity and
      effectiveness with a simultaneous study of metabolism by means of indirect
      calorimetry. Our experiments showed that an increase in the number of lever
      pressing episodes (from 1 to 8) to obtain one food granule during operant feeding
      behavior is accompanied by a progressive decrease in the level of food
      motivation. The level of food motivation remains practically unchanged with an
      increase in the ratio of pressing episodes to 16 and 32 (despite consumption of
      food). 

PMID- 25573376
TI  - Identification of MHC I class genes in two Platyrrhini species.
AB  - The major histocompatibility complex is a diverse gene family that plays a
      crucial role in the adaptive immune system. In humans, the MHC class I genes
      consist of the classical loci of HLA-A, -B, and -C, and the nonclassical loci HLA
      E, -F, and -G. In Platyrrhini species, few MHC class I genes have been described
      so far and were classified as MHC-E, MHC-F, and MHC-G, with MHC-G possibly
      representing a classical MHC class I locus while there were arguments about the
      existence of the MHC-B locus in Platyrrhini. In this study, MHC class I genes
      were identified in eight common marmosets (Callithrix jacchus) and two brown
      headed spider monkeys (Ateles fusciceps). For common marmosets, 401 cDNA
      sequences were sequenced and 18 alleles were detected, including 14 Caja-G
      alleles and 4 Caja-B alleles. Five to eleven Caja-G alleles and one to three Caja
      B alleles were detected in each animal. For brown-headed spider monkeys, 102 cDNA
      sequences were analyzed, and 9 new alleles were identified, including 5 Atfu-G
      and 4 Atfu-B alleles. Two or three Atfu-G and two Atfu-B alleles were obtained
      for each of animal. In phylogenetic analyses, the MHC-G and -B alleles from the
      two species and other Platyrrhini species show locus-specific clusters with
      bootstrap values of 86% and 50%. The results of pairwise sequence comparisons and
      an excess of non-synonymous nucleotide substitutions in the PBR region are
      consistent with the suggestion that Caja-G and Atfu-G may be classical MHC class
      I loci in the Platyrrhini species... But it appears that MHC-B locus of the two
      Platyrrhini species shares features with both classical and nonclasical MHC class
      I loci. Our results are an important addition to the limited MHC immunogenetic
      information available for the Platyrrhini species.

PMID- 25573377
TI  - Dendritic spine dynamics leading to spine elimination after repeated inductions
      of LTD.
AB  - Memory is fixed solidly by repetition. However, the cellular mechanism underlying
      this repetition-dependent memory consolidation/reconsolidation remains unclear.
      In our previous study using stable slice cultures of the rodent hippocampus, we
      found long-lasting synaptic enhancement/suppression coupled with synapse
      formation/elimination after repeated inductions of chemical LTP/LTD,
      respectively. We proposed these phenomena as useful model systems for analyzing
      repetition-dependent memory consolidation. Recently, we analyzed the dynamics of
      dendritic spines during development of the enhancement, and found that the spines
      increased in number following characteristic stochastic processes. The current
      study investigates spine dynamics during the development of the suppression. We
      found that the rate of spine retraction increased immediately leaving that of
      spine generation unaltered. Spine elimination occurred independent of the pre
      existing spine density on the dendritic segment. In terms of elimination,
      mushroom-type spines were not necessarily more stable than stubby-type and thin
      type spines. 

PMID- 25573378
TI  - Clinical significance of acquired cytogenetic clones in patients with treated
      follicular lymphoma.
AB  - BACKGROUND: Follicular lymphoma (FL) is the second most common B-cell non-Hodgkin
      lymphoma worldwide. In most patients, the disease is diagnosed at advanced stages
      and cannot be cured using conventional therapeutic approaches. To assess the role
      of cytogenetic abnormalities in therapy-related myeloid neoplasms (tMNs), we
      studied the clinicopathologic and cytogenetic features of treated FL patients who
      subsequently developed a new acquired cytogenetic clone (ACC). PATIENTS AND
      METHODS: Twenty-five treated FL patients developed new cytogenetic abnormalities
      from 2009 to 2012. Patients were divided into 3 groups based on the presence and
      absence of tMNs: group 1, ACC without tMNs after a median follow-up of 15 months;
      group 2, ACC with possible tMN after silent ACC detection; group 3, tMNs present
      at the first ACC detection. RESULTS: The most frequent cytogenetic aberrations
      involved chromosome 7. Compared with group 1, group 3 had significantly greater
      size of ACC, higher frequency of chromosome 7 aberrations, more likely showed
      dysplasia, and lower platelet count (P = .03). CONCLUSION: Our results indicate
      that the presence of ACC alone is insufficient for diagnosis of tMNs. The
      proportion of cells with specific aberrations at first ACC, bone marrow
      dysplasia, and low platelet counts might predict outcome of ACC.

PMID- 25573379
TI  - Hemozoin activates the innate immune system and reduces Plasmodium berghei
      infection in Anopheles gambiae.
AB  - BACKGROUND: Malaria is a worldwide infectious disease caused by Plasmodium
      parasites and transmitted by female Anopheles mosquitoes. The malaria vector
      mosquito Anopheles can trigger effective mechanisms to control completion of the
      Plasmodium lifecycle; the mosquito immune response to the parasite involves
      several pathways which are not yet well characterized. Plasmodium metabolite
      hemozoin has emerged as a potent immunostimulator of mammalian tissues. In this
      study, we aim to investigate the role of this parasite's by-product as stimulator
      of Anopheles gambiae immunity to Plasmodium berghei. METHODS: Female mosquitoes
      were inoculated with hemozoin and the Plasmodium infection rate and intensity
      were measured. Differences between treatments were detected by Zero-inflated
      models. Microarray transcription analysis was performed to assess gene expression
      response to hemozoin. Genome-wide analysis results were confirmed by stimulation
      of Anopheles gambiae tissues and cells with hemozoin and silencing of REL2-F and
      its negative regulator Caspar. RESULTS: Gene expression profiles revealed that
      hemozoin activates several immunity genes, including pattern recognition
      receptors (PRRs) and antimicrobial peptides (AMPs). Importantly, we found that
      the Immune deficiency (Imd) pathway Nuclear Factor-kappaB (NF-kappaB)
      transcription factor REL2, in its full-length form REL2-F, was induced upon
      hemozoin treatment. CONCLUSIONS: We have for the first time shown the impact of
      hemozoin treatment in Plasmodium infection, reducing both rate and intensity of
      the infection. We propose that hemozoin boosts the innate immunity in Anopheles,
      activating key effector genes involved in mosquito resistance to Plasmodium, and
      this activation is REL2-mediated.

PMID- 25573380
TI  - A Novel CDC25B Promoter-Based Oncolytic Adenovirus Inhibited Growth of Orthotopic
      Human Pancreatic Tumors in Different Preclinical Models.
AB  - PURPOSE: We decided to construct a novel oncolytic adenovirus whose replication
      was driven by the CDC25B promoter for its use in preclinical models of pancreatic
      cancer. EXPERIMENTAL DESIGN: We placed the essential E1A gene under control of
      the CDC25B promoter. Based on preliminary data, we pseudotyped the adenovirus
      with a chimeric fiber of serotypes 5/3. We investigated the in vitro lytic effect
      and the in vivo therapeutic efficacy in combination with gemcitabine on human
      pancreatic tumor xenografts orthotopically growing in nude mice and in tumors
      growing in Syrian hamsters. We also assessed biochemical markers of hepatic
      toxicity and CA19.9 levels. RESULTS: AV25CDC exhibited a strong in vitro lytic
      effect on pancreatic cancer cells. In vivo administration of AV25CDC combined
      with gemcitabine in mice harboring subcutaneously growing SW1990 pancreatic
      tumors almost abrogated tumor growth. Nude mice harboring 15-day-old orthotopic
      tumors, treated intratumorally or systemically with AV25CDC combined with
      gemcitabine, exhibited 70% to 80% reduction in tumor size compared with control
      mice that lasted for at least 60 days. Chemovirotherapy treatment induced a
      return to normal levels of biochemical parameters of hepatic toxicity; these mice
      exhibited more than 90% reduction in CA19.9 serum levels compared with control.
      Chemovirotherapy efficacy was confirmed in mice harboring Mia PaCa-2 tumors and
      in Syrian hamster harboring HaP-T1 tumors. We observed that viral treatment
      disrupted tumor architecture and induced an increase in MMP-9 activity that might
      facilitate gemcitabine penetrability. CONCLUSION: These data demonstrate that
      AV25CDC is an effective oncolytic agent candidate for pancreatic cancer
      chemovirotherapy combination.

PMID- 25573381
TI  - Effective targeting of the P53-MDM2 axis in preclinical models of infant MLL
      rearranged acute lymphoblastic leukemia.
AB  - PURPOSE: Although the overall cure rate for pediatric acute lymphoblastic
      leukemia (ALL) approaches 90%, infants with ALL harboring translocations in the
      mixed-lineage leukemia (MLL) oncogene (infant MLL-ALL) experience shorter
      remission duration and lower survival rates (~50%). Mutations in the p53 tumor
      suppressor gene are uncommon in infant MLL-ALL, and drugs that release p53 from
      inhibitory mechanisms may be beneficial. The purpose of this study was to assess
      the efficacy of the orally available nutlin, RG7112, against patient-derived MLL
      ALL xenografts. EXPERIMENTAL DESIGN: Eight MLL-ALL patient-derived xenografts
      were established in immune-deficient mice, and their molecular features compared
      with B-lineage ALL and T-ALL xenografts. The sensitivity of MLL-ALL xenografts to
      RG7112 was assessed in vitro and in vivo, and the ability of RG7112 to induce
      p53, cell-cycle arrest, and apoptosis in vivo was evaluated. RESULTS: Gene
      expression analysis revealed that MLL-ALL, B-lineage ALL, and T-ALL xenografts
      clustered according to subtype. Moreover, genes previously reported to be
      overexpressed in MLL-ALL, including MEIS1, CCNA1, and members of the HOXA family,
      were significantly upregulated in MLL-ALL xenografts, confirming their ability to
      recapitulate the clinical disease. Exposure of MLL-ALL xenografts to RG7112 in
      vivo caused p53 upregulation, cell-cycle arrest, and apoptosis. RG7112 as a
      single agent induced significant regressions in infant MLL-ALL xenografts.
      Therapeutic enhancement was observed when RG7112 was assessed using combination
      treatment with an induction-type regimen (vincristine/dexamethasone/L
      asparaginase) against an MLL-ALL xenograft. CONCLUSIONS: The utility of targeting
      the p53-MDM2 axis in combination with established drugs for the management of
      infant MLL-ALL warrants further investigation.

PMID- 25573382
TI  - Zebrafish: a new companion for translational research in oncology.
AB  - In an era of high-throughput "omic" technologies, the unprecedented amount of
      data that can be generated presents a significant opportunity but simultaneously
      an even greater challenge for oncologists trying to provide personalized
      treatment. Classically, preclinical testing of new targets and identification of
      active compounds against those targets have entailed the extensive use of
      established human cell lines, as well as genetically modified mouse tumor models.
      Patient-derived xenografts in zebrafish may in the near future provide a platform
      for selecting an appropriate personalized therapy and together with zebrafish
      transgenic tumor models represent an alternative vehicle for drug development.
      The zebrafish is readily genetically modified. The transparency of zebrafish
      embryos and the recent development of pigment-deficient zebrafish afford
      researchers the valuable capacity to observe directly cancer formation and
      progression in a live vertebrate host. The zebrafish is amenable to
      transplantation assays that test the serial passage of fluorescently labeled
      tumor cells as well as their capacity to disseminate and/or metastasize. Progress
      achieved to date in genetic engineering and xenotransplantation will establish
      the zebrafish as one of the most versatile animal models for cancer research. A
      model organism that can be used in transgenesis, transplantation assays, single
      cell functional assays, and in vivo imaging studies make zebrafish a natural
      companion for mice in translational oncology research.

PMID- 25573383
TI  - A Phase I Study of CUDC-101, a Multitarget Inhibitor of HDACs, EGFR, and HER2, in
      Combination with Chemoradiation in Patients with Head and Neck Squamous Cell
      Carcinoma.
AB  - PURPOSE: CUDC-101 is a small molecule that simultaneously inhibits the epidermal
      growth factor receptor (EGFR), human growth factor receptor 2 (HER2), and histone
      deacetylase (HDAC) with preclinical activity in head and neck squamous cell
      cancer (HNSCC). The primary objective of this investigation is to determine the
      maximum tolerated dose (MTD) of CUDC-101 with cisplatin-radiotherapy in the
      treatment of HNSCC. EXPERIMENTAL DESIGN: CUDC-101 monotherapy was administered
      intravenously three times weekly (Monday, Wednesday, Friday) for a one-week run
      in, then continued with concurrent cisplatin (100 mg/m(2) every 3 weeks) and
      external beam radiation (70 Gy to gross disease) over 7 weeks. RESULTS: Twelve
      patients with intermediate or high-risk HNSCC enrolled. Eleven were p16INKa (p16)
      negative. The MTD of CUDC-101-based combination therapy was established at 275
      mg/m(2)/dose. Five patients discontinued CUDC-101 due to an adverse event (AE);
      only one was considered a dose-limiting toxicity (DLT), at the MTD.
      Pharmacokinetic evaluation suggested low accumulation with this dosing regimen.
      HDAC inhibition was demonstrated by pharmacodynamic analyses in peripheral blood
      mononuclear cells (PBMC), tumor biopsies, and paired skin biopsies. Paired tumor
      biopsies demonstrated a trend of EGFR inhibition. At 1.5 years of median follow
      up, there has been one recurrence and two patient deaths (neither attributed to
      CUDC-101). The remaining nine patients are free of progression. CONCLUSIONS: CUDC
      101, cisplatin, and radiation were feasible in intermediate-/high-risk patients
      with HNSCC, with no unexpected patterns of AE. Although the MTD was identified, a
      high rate of DLT-independent discontinuation of CUDC-101 suggests a need for
      alternate schedules or routes of administration.

PMID- 25573384
TI  - Electronic nicotine delivery systems: a policy statement from the American
      Association for Cancer Research and the American Society of Clinical Oncology.
AB  - Combustible tobacco use remains the number one preventable cause of disease,
      disability, and death in the United States. Electronic nicotine delivery systems
      (ENDS), which include e-cigarettes, are devices capable of delivering nicotine in
      an aerosolized form. ENDS use by both adults and youth has increased rapidly, and
      some have advocated these products could serve as harm-reduction devices and
      smoking cessation aids. ENDS may be beneficial if they reduce smoking rates or
      prevent or reduce the known adverse health effects of smoking. However, ENDS may
      also be harmful, particularly to youth, if they increase the likelihood that
      nonsmokers or formers smokers will use combustible tobacco products or if they
      discourage smokers from quitting. The American Association for Cancer Research
      (AACR) and the American Society of Clinical Oncology (ASCO) recognize the
      potential ENDS have to alter patterns of tobacco use and affect the public's
      health; however, definitive data are lacking. AACR and ASCO recommend additional
      research on these devices, including assessing the health impacts of ENDS,
      understanding patterns of ENDS use, and determining what role ENDS have in
      cessation. Key policy recommendations include supporting federal, state, and
      local regulation of ENDS; requiring manufacturers to register with the FDA and
      report all product ingredients, requiring childproof caps on ENDS liquids, and
      including warning labels on products and their advertisements; prohibiting youth
      oriented marketing and sales; prohibiting child-friendly ENDS flavors; and
      prohibiting ENDS use in places where cigarette smoking is prohibited.

PMID- 25573385
TI  - The role of eicosanoids in 17alpha, 20beta-dihydroxy-4-pregnen-3-one-induced
      ovulation and spawning in Danio rerio.
AB  - This study employed a hormone bioassay to characterize the eicosanoids involved
      in zebrafish ovulation and spawning, in particular the prostaglandin (PG)
      products of cyclooxygenase (COX) metabolism and the leukotriene (LT) products of
      lipoxygenase (LOX) metabolism. Exposure to the teleost progestogen 17alpha,
      20beta-dihydroxy-4-pregnen-3-one (17,20betaP) induced ovulation, but not
      spawning, in solitary females and both ovulation and spawning in male-female
      pairs. Transcription of the eicosanoid-synthesizing enzymes cytosolic
      phospholipase A2 (cPLA(2)) and COX-2 increased and LTC(4) synthase decreased in
      peri-ovulatory ovaries of 17,20betaP-exposed fish. Ovarian PGF(2alpha) levels
      increased post-spawning in 17,20betaP-exposed fish, but there was no difference
      in LTB(4) or LTC(4). Pre-exposure to cPLA(2) or LOX inhibitors reduced 17,20betaP
      induced ovulation rates, while a COX inhibitor had no effect on ovulation or
      spawning. Collectively, these findings suggest that eicosanoids, in particular
      LOX metabolites, mediate 17,20betaP-induced ovulation in zebrafish. COX
      metabolites also appear to be involved in ovulation and spawning but their role
      remains undefined.

PMID- 25573386
TI  - Reinnervation following catheter-based radio-frequency renal denervation.
AB  - NEW FINDINGS: What is the topic of this review? Does catheter-based renal
      denervation effectively denervate the afferent and efferent renal nerves and does
      reinnervation occur? What advances does it highlight? Following catheter-based
      renal denervation, the afferent and efferent responses to electrical stimulation
      were abolished, renal sympathetic nerve activity was absent, and levels of renal
      noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin
      gene-related peptide were significantly reduced. By 11 months after renal
      denervation, both the functional responses and anatomical markers of afferent and
      efferent renal nerves had returned to normal, indicating reinnervation. Renal
      denervation reduces blood pressure in animals with experimental hypertension and,
      recently, catheter-based renal denervation was shown to cause a prolonged
      decrease in blood pressure in patients with resistant hypertension. The
      randomized, sham-controlled Symplicity HTN-3 trial failed to meet its primary
      efficacy end-point, but there is evidence that renal denervation was incomplete
      in many patients. Currently, there is little information regarding the
      effectiveness of catheter-based renal denervation and the extent of
      reinnervation. We assessed the effectiveness of renal nerve denervation with the
      Symplicity Flex catheter and the functional and anatomical reinnervation at 5.5
      and 11 months postdenervation. In anaesthetized, non-denervated sheep, there was
      a high level of renal sympathetic nerve activity, and electrical stimulation of
      the renal nerve increased blood pressure and reduced heart rate (afferent
      response) and caused renal vasoconstriction and reduced renal blood flow
      (efferent response). Immediately after renal denervation, renal sympathetic nerve
      activity and the responses to electrical stimulation were absent, indicating
      effective denervation. By 11 months after denervation, renal sympathetic nerve
      activity was present and the responses to electrical stimulation were normal,
      indicating reinnervation. Anatomical measures of renal innervation by sympathetic
      efferent nerves (tissue noradrenaline and tyrosine hydroxylase) and afferent
      sensory nerves (calcitonin gene-related peptide) demonstrated large decreases at
      1 week postdenervation, but normal levels at 11 months postdenervation. In
      summary, catheter-based renal denervation is effective, but reinnervation occurs.
      Studies of central and renal changes postdenervation are required to understand
      the causes of the prolonged hypotensive response to catheter-based renal
      denervation in human hypertension.

PMID- 25573387
TI  - The use of dermal graft in severe chordee hypospadias repair: experience from
      Vietnam.
AB  - PURPOSE: Severe chordee with hypospadias may require repair by ventral
      corporoplasty with a free graft before urethroplasty. We report an 11 year
      experience with one-stage and two-stage hypospadias repair using dermal grafts.
      MATERIALS AND METHODS: From 12/1997 to 12/2008, 47 hypospadias with severe
      chordee were repaired using a ventral dermal graft to correct the chordee. Forty
      cases were repaired in two stages; the remaining seven patients had adequate
      preputial skin and were repaired in one stage. In 28 cases the neourethra was
      covered with both tunica vaginalis and penile dartos flap while 12 were covered
      only with penile dartos flap. Patients ranged from 12 to 152 months of age.
      Follow-up ranged from 6 months to 4 years. RESULTS: 28 patients with both tunica
      vaginalis and dartos flap had 7 urethral fistulas and 2 developed meatal
      stenosis. 12 patients with only penile dartos flap had 3 fistulas and 2 had
      meatal regression. The seven patients who underwent a one-stage repair had good
      results with a straight penis and no evidence of urethral fistula or urethral
      stenosis. CONCLUSIONS: Dermal graft can be performed in one or two stage
      hypospadias repair. Complication rates are similar to other standard repairs for
      proximal hypospadias.

PMID- 25573388
TI  - Use of the amicyanin signal sequence for efficient periplasmic expression in E.
      coli of a human antibody light chain variable domain.
AB  - Periplasmic localization of recombinant proteins offers advantages over
      cytoplasmic protein expression. In this study signal sequence of amicyanin, which
      is encoded by the mauC gene of Paracoccus denitrificans, was used to express the
      light chain variable domain of the human kappaIO8/O18 germline antibody in the
      periplasm of Escherichiacoli. The expressed protein was purified in good yield
      (70mg/L of culture) in one step from the periplasmic fraction by affinity
      chromatography using an engineered hexahistidine tag. Circular dichroism
      spectroscopy was used to determine if the secondary and tertiary structures of
      the protein and its thermal stability corresponded to those of the native folded
      protein. The expressed and purified protein was indeed properly folded and
      exhibited a reasonable thermal transition temperature of 53 degrees C. These
      results indicate that the amicyanin signal sequence may be particularly useful
      for prokaryotic expression of proteins which are prone to mis-folding,
      aggregation or formation of inclusion bodies, all of which were circumvented in
      this study. 

PMID- 25573389
TI  - Expression, purification and characterization of Solanum tuberosum recombinant
      cytosolic pyruvate kinase.
AB  - The cDNA encoding for a Solanum tuberosum cytosolic pyruvate kinase 1 (PKc1)
      highly expressed in tuber tissue was cloned in the bacterial expression vector
      pProEX HTc. The construct carried a hexahistidine tag in N-terminal position to
      facilitate purification of the recombinant protein. Production of high levels of
      soluble recombinant PKc1 in Escherichia coli was only possible when using a co
      expression strategy with the chaperones GroES-GroEL. Purification of the protein
      by Ni(2 +) chelation chromatography yielded a single protein with an apparent
      molecular mass of 58kDa and a specific activity of 34unitsmg(-1) protein. The
      recombinant enzyme had an optimum pH between 6 and 7. It was relatively heat
      stable as it retained 80% of its activity after 2min at 75 degrees C. Hyperbolic
      saturation kinetics were observed with ADP and UDP whereas sigmoidal saturation
      was observed during analysis of phosphoenolpyruvate binding. Among possible
      effectors tested, aspartate and glutamate had no effect on enzyme activity,
      whereas alpha-ketoglutarate and citrate were the most potent inhibitors. When
      tested on phosphoenolpyruvate saturation kinetics, these latter compounds
      increased S0.5. These findings suggest that S. tuberosum PKc1 is subject to a
      strong control by respiratory metabolism exerted via citrate and other
      tricarboxylic acid cycle intermediates. 

PMID- 25573390
TI  - Fresh osteochondral allograft transplantation for bipolar reciprocal
      osteochondral lesions of the knee.
AB  - BACKGROUND: Osteochondral allograft (OCA) transplantation is an effective
      treatment option for chondral and osteochondral defects of the knee. HYPOTHESIS:
      Patients treated with OCAs for reciprocal bipolar lesions of the knee would
      demonstrate significant clinical improvement. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: Between 1983 and 2010, OCAs were implanted for bipolar
      chondral lesions in 46 patients (48 knees). The 21 male and 25 female patients
      averaged 40 years of age (range, 15-66 years). Thirty-four lesions were
      tibiofemoral, and 14 were patellofemoral. Forty-two knees (88%) had undergone a
      mean of 3.4 previous surgeries (range, 1-8). The mean allograft area was 19.2
      cm(2). Clinical evaluation included the modified Merle d'Aubigne-Postel (18
      point), International Knee Documentation Committee (IKDC) pain and function, and
      Knee Society function (KS-F) scores. Further surgeries on the operative joint
      were documented. RESULTS: Survivorship of the bipolar OCA was 64.1% at 5 years.
      Thirty knees underwent further surgery; 22 knees (46%) were considered failures
      (3 OCA revisions, 14 total knee arthroplasties, 2 unicondylar arthroplasties, 2
      arthrodeses, and 1 patellectomy). Among patients whose OCA was still in situ at
      follow-up, the mean follow-up was 7 years (range, 2.0-19.7 years). The mean 18
      point score improved from 12.1 to 16.1; 88% (23/26 knees) of surviving allografts
      scored >=15. The mean IKDC pain score improved from 7.5 to 4.7, and the mean IKDC
      function score improved from 3.4 to 7.0. The mean KS-F score improved from 70.5
      to 84.1. CONCLUSION: Osteochondral allograft transplantation is a useful salvage
      treatment option for reciprocal bipolar cartilage lesions of the knee. High
      reoperation and failure rates were observed, but patients with surviving
      allografts showed significant clinical improvement.

PMID- 25573391
TI  - Return to play after chondroplasty of the knee in National Football League
      athletes.
AB  - BACKGROUND: Knee injuries, including articular cartilage damage, are common in
      football players and are potentially career threatening. The rate of return to
      play (RTP) as well as the factors affecting return after arthroscopic
      chondroplasty of the knee is performed in National Football League (NFL) athletes
      are not known. PURPOSE: To determine the rate of return to regular season NFL
      competition after arthroscopic knee surgery including chondroplasty of articular
      cartilage lesions. In addition, identification of factors that influence
      successful return was investigated. STUDY DESIGN: Case series; Level of evidence,
      4. METHODS: Athletes in the NFL who underwent arthroscopic chondroplasty at a
      single institution were identified. Retrospective chart review and review of the
      NFL online database were utilized to determine the rate of RTP and factors
      affecting an athlete's ability to return. Chi-square and Student t tests were
      used to assess differences among players who were and were not able to RTP, and
      logistic regression was employed to determine a player's odds of return. RESULTS:
      There were 52 patients (54 procedures) identified from the surgical database who
      met the inclusion criteria for the study operated on between August 1, 2001, and
      March 31, 2011. Of these players, 36 (67%) were able to return to regular season
      NFL game play at an average of 8.2 months, including 13 (24%) who were still
      active in the NFL. The average time to follow-up was 5.9 years, and all players
      were allowed at least 2 years of follow-up. There was no significant correlation
      of RTP to athlete age, lesion size, lesion location, position played, or round
      selected in the NFL draft. Players who underwent concomitant microfracture were
      4.4 times less likely to return to the NFL than were those who did not undergo
      this procedure (95% CI, 1.3-15.5). Athletes who played more than 11.6 games per
      season were 4.7 times more likely to RTP than were those who played fewer games
      per season (95% CI, 1.4-16.6). Athletes who returned to play competed in 56 fewer
      games, 3.3 fewer seasons, and played in 3.2 fewer games per season compared with
      their level of competition before surgery. CONCLUSION: A majority (67%) of NFL
      players are able to RTP after arthroscopic knee surgery including chondroplasty
      of articular cartilage lesions. Athletes who play more games per season are more
      likely to RTP after chondroplasty of articular cartilage lesions of the knee, but
      those undergoing concomitant microfracture are less likely to return. No
      statistical significance was determined when comparing the athletes who returned
      to play with respect to age at surgery, lesion location, lesion size, lesion
      grade, position that the athlete played, or draft round.

PMID- 25573392
TI  - Do patient age and sex influence tendon cell biology and clinical/radiographic
      outcomes after rotator cuff repair?
AB  - BACKGROUND: Many clinical and radiographic studies suggest that patient age and
      sex have an influence on rotator cuff (RC) repair outcomes. However, these
      findings result from retrospective statistical analyses and cannot provide a
      causal answer. PURPOSE: To analyze whether age and sex influence the biological
      potential at the time of RC repair or midterm clinical and radiographic outcomes.
      Also assessed was the effect of the biological potential on intraindividual
      clinical/radiographic results. STUDY DESIGN: Cohort study; Level of evidence, 2.
      METHODS: A total of 40 patients underwent arthroscopic RC repair. At the time of
      surgery (t = 0), supraspinatus tendon biopsy specimens were obtained, cultivated,
      and assessed for their biological potential, particularly (1) cell growth and (2)
      collagen type I production. After a follow-up at 24 months (t = 1), all patients
      were assessed by clinical scores (Constant score, subjective shoulder value,
      American Shoulder and Elbow Surgeons [ASES] score, and Western Ontario Rotator
      Cuff Index [WORC] score) and underwent magnetic resonance imaging to determine RC
      integrity. The data were examined for age- and sex-related differences and to
      identify the correlation between biological potential (t = 0) and
      clinical/radiographic outcome (t = 1). RESULTS: The follow-up rate for the
      imaging and clinical evaluation was 100%. Age, but not sex, influenced the
      biological tendon cell parameters at t = 0. However, there was no effect of age
      or sex on the clinical and radiographic results at t = 1. Furthermore, no
      correlation was observed between the initial biological parameters and later
      clinical outcomes or radiographic RC integrity. Finally, there was no significant
      difference between intact and nonhealed repairs in terms of the respective
      clinical scores. CONCLUSION: Age, but not sex, was found to have a negative
      effect on RC tendon cell biology. However, neither sex nor, in particular, a
      higher age influenced repair outcomes after 24 months.

PMID- 25573393
TI  - Biomechanical evaluation of the transtibial pull-out technique for posterior
      medial meniscal root repairs using 1 and 2 transtibial bone tunnels.
AB  - BACKGROUND: Current methods of the transtibial pull-out meniscal root repair
      significantly displace under cyclic loading in porcine models but have not been
      evaluated in human models. One potential explanation for the displacement is that
      a single transtibial tunnel may not fully restore the attachment of the entire
      posterior medial meniscal root. PURPOSE/HYPOTHESIS: The purpose of this study was
      to biomechanically evaluate the transtibial pull-out technique in a human
      cadaveric model using either 1 or 2 transtibial bone tunnels. The hypothesis was
      that a transtibial pull-out technique using 2 transtibial bone tunnels would
      confer superior biomechanical properties in comparison to an iteration using 1
      transtibial bone tunnel. STUDY DESIGN: Controlled laboratory study. METHODS: Ten
      matched pairs of male human cadaveric knees (average age, 52.7 years) were
      randomly assigned (1 each of the pair) to 2 groups consisting of a transtibial
      pull-out technique using either 1 or 2 transtibial bone tunnels. The knees were
      cyclically loaded for 1000 cycles from 10 to 30 N at 0.5 Hz, representing the
      loads experienced during a typical meniscal root repair postoperative
      rehabilitation program, and then pulled to failure at a rate of 0.5 mm/s.
      RESULTS: Differences between 1- and 2-tunnel repair groups were neither
      statistically nor clinically significant with respect to displacement or ultimate
      failure load. On average, the 1- and 2-tunnel repair groups resulted in 3.32 mm
      and 3.23 mm of displacement, respectively, after 1000 testing cycles. At 1, 100,
      500, and 1000 testing cycles, displacement was not significantly different
      between groups (P > .799). The 2-tunnel repair technique resulted in a 10.2%
      higher ultimate failure load (135 N vs. 123 N); however, this was not significant
      (P = .333). CONCLUSIONS: Similar biomechanical properties were seen between
      transtibial pull-out repairs using either 1 or 2 transtibial bone tunnels in a
      human cadaveric model. Both repair groups exceeded the 3-mm threshold for
      nonanatomic displacement. CLINICAL RELEVANCE: This study indicates that a newly
      proposed iteration of the transtibial pull-out repair technique using a second
      transtibial tunnel, which theoretically restores more of the posterior medial
      meniscal root, was almost identical to the current clinical standard involving a
      single transtibial tunnel. As the importance of repairing meniscal root tears is
      increasingly recognized, further studies on new iterations of both techniques are
      warranted to minimize the risk of displacement caused by early motion in the
      initial postoperative rehabilitation period.

PMID- 25573394
TI  - The Use of Cryotherapy for Papilloma and Early Laryngeal Cancers: Long-term
      Results.
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVE: To determine the efficacy of
      adjuvant cryotherapy in the treatment of early glottic cancer and laryngeal
      papillomatosis. SUMMARY OF BACKGROUND DATA: The use of cryotherapy in conjunction
      with traditional modalities has recently been proposed to improve voice outcomes
      in patients with early laryngeal cancer as compared to pretreatment conditions.
      This study investigates its utility in improving oncological outcomes and
      decreasing recurrences of laryngeal papillomatosis. METHODS: Patients with either
      early glottic cancer or laryngeal papillomatosis that received cryotherapy as
      part of their surgical regimen were investigated. All patients were seen at a
      large tertiary care center within a 10-year window. Demographic data were
      collected and all postoperative notes were reviewed. Recurrences of the laryngeal
      cancer were noted, as was the duration of time between successive papillomatosis
      operations. RESULTS: The charts of 54 glottic cancer and 29 papillomatosis
      patients that received cryotherapy were reviewed. One patient from the
      papillomatosis cohort was excluded from statistical analysis due to lack of
      follow-up. Overall, 16 (30%) of the laryngeal cancer patient experienced a
      malignant recurrence. The overall 5-year survival of these patients was 98% and
      the 5-year disease-free survival was 74%. The use of adjuvant cryotherapy in the
      treatment of laryngeal papillomatosis extended the duration of time between
      surgeries by an average of 79 days (P=.23). CONCLUSION: The use of adjuvant
      cryotherapy in the treatment of early glottic cancer does not improve the rate of
      carcinoma recurrences. Additionally, cryotherapy does not result in a
      statistically significant increase in the duration of disease-free period for
      laryngeal papillomatosis patients, although the observed increase may be
      clinically important.

PMID- 25573395
TI  - Renaming schizophrenia to reduce stigma: comparison with the case of bipolar
      disorder.
AB  - Renaming disorders to change public beliefs and attitudes remains controversial.
      This study compared the potentially destigmatising effects of renaming
      schizophrenia with the effects of renaming bipolar disorder by comparing the
      label 'schizophrenia' to 'integration disorder', and 'bipolar disorder' to 'manic
      depression', in 1621 lay participants. 'Bipolar disorder' was associated with
      less fear and social distance than 'manic depression'. 'Integration disorder' was
      associated with increased endorsement of a biopsychosocial cause and reduced
      attributions of dangerousness but also increased social distance, highlighting
      the complex effects renaming has on stigma. 

PMID- 25573396
TI  - Neural responses to dynamic multimodal stimuli and pathology-specific impairments
      of social cognition in schizophrenia and depression.
AB  - BACKGROUND: Individuals with schizophrenia and people with depression both show
      abnormal behavioural and neural responses when perceiving and responding to
      emotional stimuli, but pathology-specific differences and commonalities remain
      mostly unclear. AIMS: To directly compare empathic responses to dynamic
      multimodal emotional stimuli in a group with schizophrenia and a group with
      depression, and to investigate their neural correlates using functional magnetic
      resonance imaging (fMRI). METHOD: The schizophrenia group (n = 20), the
      depression group (n = 24) and a control group (n = 24) were presented with
      portrait-shot video clips expressing emotion through three possible communication
      channels: facial expression, prosody and content. Participants rated their own
      and the actor's emotional state as an index of empathy. RESULTS: Although no
      group differences were found in empathy ratings, characteristic differences
      emerged in the fMRI activation patterns. The schizophrenia group demonstrated
      aberrant activation patterns during the neutral speech content condition in
      regions implicated in multimodal integration and formation of semantic
      constructs. Those in the depression group were most affected during conditions
      with trimodal emotional and trimodal neutral stimuli, in key regions of the
      mentalising network. CONCLUSIONS: Our findings reveal characteristic differences
      in patients with schizophrenia compared with those with depression in their
      cortical responses to dynamic affective stimuli. These differences indicate that
      impairments in responding to emotional stimuli may be caused by pathology
      specific problems in social cognition.

PMID- 25573397
TI  - Latent structure of the proposed ICD-11 post-traumatic stress disorder symptoms:
      implications for the diagnostic algorithm.
AB  - BACKGROUND: The latent structure of the proposed ICD-11 post-traumatic stress
      disorder (PTSD) symptoms has not been explored. AIMS: To investigate the latent
      structure of the proposed ICD-11 PTSD symptoms. METHOD: Confirmatory factor
      analyses using data from structured clinical interviews administered to injury
      patients (n = 613) 6 years post-trauma. Measures of disability and psychological
      quality of life (QoL) were also administered. RESULTS: Although the three-factor
      model implied by the ICD-11 diagnostic criteria fit the data well, a two-factor
      model provided equivalent, if not superior, fit. Whereas diagnostic criteria
      based on this two-factor model resulted in an increase in PTSD point prevalence
      (5.1% v. 3.4%; z = 2.32, P<0.05), they identified individuals with similar levels
      of disability (P = 0.933) and QoL (P = 0.591) to those identified by the ICD-11
      criteria. CONCLUSIONS: Consistent with theorised reciprocal relationships between
      re-experiencing and avoidance in PTSD, these findings support an alternative
      diagnostic algorithm requiring at least two of any of the four re
      experiencing/avoidance symptoms and at least one of the two hyperarousal
      symptoms.

PMID- 25573398
TI  - Gender differences in outcomes in people with schizophrenia in rural China: 14
      year follow-up study.
AB  - BACKGROUND: Little is known about gender differences in the long-term outcomes of
      people with schizophrenia living in the community. AIMS: To explore gender
      differences in the 14-year outcome of people with schizophrenia in rural China.
      METHOD: A 14-year follow-up study among a 1994 cohort (n = 510) of participants
      with schizophrenia was conducted in Xinjin County, Chengdu, China. All
      participants and their informants were followed up in 2004 and 2008 using the
      Patients Follow-up Schedule. RESULTS: Compared with female participants, male
      participants were significantly younger, had significantly higher rates of
      mortality, suicide and homelessness, and poorer family and social support. There
      was no significant gender difference in Positive and Negative Syndrome Scale
      scores, previous suicide attempts, those never treated, previous hospital
      admission or inability to work. Longer duration of illness was associated with
      functional decline and comparatively poorer family economic status. CONCLUSIONS:
      The long-term outcomes of men with schizophrenia is worse than those of women
      with the disorder in rural China. Higher mortality, suicide and homelessness
      rates in men may contribute partly to the higher prevalence of schizophrenia in
      women in China. Policies on social and family support and gender-specific
      intervention strategies for improving long-term outcomes should be developed for
      people with this disorder.

PMID- 25573399
TI  - Common and disorder-specific neural responses to emotional faces in generalised
      anxiety, social anxiety and panic disorders.
AB  - BACKGROUND: Although evidence exists for abnormal brain function across various
      anxiety disorders, direct comparison of neural function across diagnoses is
      needed to elicit abnormalities common across disorders and those distinct to a
      particular diagnosis. AIMS: To delineate common and distinct abnormalities within
      generalised anxiety (GAD), panic and social anxiety disorder (SAD) during
      affective processing. METHOD: Fifty-nine adults (15 with GAD, 15 with panic
      disorder, 14 with SAD, and 15 healthy controls) underwent functional magnetic
      resonance imaging while completing a facial emotion matching task with fearful,
      angry and happy faces. RESULTS: Greater differential right amygdala activation to
      matching fearful v. happy facial expressions related to greater negative
      affectivity (i.e. trait anxiety) and was heightened across all anxiety disorder
      groups compared with controls. Collapsing across emotional face types,
      participants with panic disorder uniquely displayed greater posterior insula
      activation. CONCLUSIONS: These preliminary results highlight a common neural
      basis for clinical anxiety in these diagnoses and also suggest the presence of
      disorder-specific dysfunction.

PMID- 25573400
TI  - Effect of long-term supplementation with folic acid and B vitamins on risk of
      depression in older women.
AB  - BACKGROUND: Homocysteine-lowering nutrients may have preventive/ameliorative
      roles in depression. AIMS: To test whether long-term B-vitamin/folate
      supplementation reduces depression risk. METHOD: Participants were 4331 women
      (mean age 63.6 years), without prior depression, from the Women's Antioxidant and
      Folic Acid Cardiovascular Study - a randomised controlled trial of cardiovascular
      disease prevention among 5442 women. Participants were randomly assigned to
      receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d) and vitamin
      B12 (1 mg/d) or a matching placebo. Average treatment duration was 7 years. The
      outcome was incident depression, defined as self-reported physician/clinician
      diagnosed depression or clinically significant depressive symptoms. RESULTS:
      There were 524 incident cases. There was no difference between active v. placebo
      groups in depression risk (adjusted relative risk 1.02, 95% CI 0.86-1.21, P =
      0.81), despite significant homocysteine level reduction. CONCLUSIONS: Long-term,
      high-dose, daily supplementation with folic acid and vitamins B6 and B12 did not
      reduce overall depression risk in mid-life and older women.

PMID- 25573401
TI  - [Plastic surgery options for the treatment of chronic foot ulcers].
AB  - BACKGROUND: A large number of possibilities to cover chronic ulcers are
      available. The special aspects of the diabetic foot need to be considered when
      selecting a flap design for coverage. OBJECTIVES: The purpose of this work is to
      discuss which plastic surgery techniques are preferred when treating chronic
      ulcers of the diabetic foot. MATERIALS AND METHODS: Analysis of our own cases and
      discussion of basic literature. RESULTS: Muscle flaps generally have better
      perfusion and increased angiogenic activity than skin flaps and, therefore, have
      better results in the treatment of chronic wounds. Especially important when
      choosing a procedure for the treatment of the diabetic foot is the situation of
      vessels and perfusion. CONCLUSIONS: An interdisciplinary approach with internal,
      orthopedic, and radiological specialists from the beginning of the treatment is
      the basis for success. The pedicled myocutaneous instep flap with inclusion of
      the abductor hallucis muscle allows stable coverage in the weight bearing area to
      be obtained. Free flaps like the anterolateral thigh flap should be raised
      including a muscle (part of vastus lateralis muscle) to achieve multilayer
      coverage. Postoperative wound care and training of the flap by the patient are
      also important for successful treatment and need to be guaranteed in advance.

PMID- 25573402
TI  - Associations of toll-like receptor (TLR)-4 single nucleotide polymorphisms and
      rheumatoid arthritis disease progression: an observational cohort study.
AB  - OBJECTIVE: To examine the associations of toll-like receptor (TLR)-4 single
      nucleotide polymorphisms (SNPs) with disease progression in rheumatoid arthritis
      (RA). METHODS: A total of 1188 RA patients were genotyped for TLR4 SNPs
      (rs1927911, rs11536878, and rs4986790). Measures of disease activity were
      examined, including Disease Activity Score-28 (DAS28), Multidimensional Health
      Assessment Questionnaire (MD-HAQ), Clinical Disease Activity Index (CDAI), and
      Simplified Disease Activity Index (SDAI). Genetic associations with these
      longitudinal measures were examined using generalized estimating equations in
      both univariate and multivariate analyses. Analyses were then stratified by
      antigen specific anti-citrullinated peptide antibody (ACPA) status including
      antibody to citrullinated fibrinogen and citrullinated histone H2B. RESULTS:
      Disease activity measures progressed less over time in the homozygous minor
      allele group of rs1927911 including DAS28 (p<0.001), CDAI (p=0.008), and MD-HAQ
      (p=0.015) in univariate analysis and DAS28, CDAI and SDAI in multivariate
      analysis. Disease activity progression among those homozygous for the minor
      allele tended to be lower in the groups with positive ACPA though major
      differences by autoantibody status were not identified. There were no
      associations of TLR4 rs11536878 and rs4986790 SNPs with RA disease activity
      progression. CONCLUSIONS: In this population, TLR4 rs1927911 genotypes are
      associated with disease activity independent of other covariates.

PMID- 25573403
TI  - Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2
      responses and airway inflammation in mice.
AB  - Zerumbone is a sesquiterpene compound isolated from the rhizome of wild ginger,
      Zingiber zerumbet Smith. The rhizomes of the plant are used as a spice and
      traditional medicine. Zerumbone was shown to possess anticarcinogenic, anti
      inflammatory, and antioxidant properties. However, the antiallergic activity and
      the underlying mechanism of zerumbone have not been reported. Herein, we
      investigated the immunomodulatory effects of zerumbone on antigen-presenting
      dendritic cells (DCs) in vitro and its potential therapeutic effects against
      ovalbumin (OVA)-induced T helper 2 (Th2)-mediated asthma in mice. In the presence
      of zerumbone, lipopolysaccharide-activated bone marrow-derived DCs enhanced T
      cell proliferation and Th1 cell polarization in an allogeneic mixed lymphocyte
      reaction. In animal experiments, mice were sensitized and challenged with OVA,
      and were orally treated with different doses of zerumbone after sensitization.
      Circulating titers of OVA-specific antibodies, airway hyperresponsiveness to
      methacholine, histological changes in lung tissues, the cell composition and
      cytokine levels in bronchoalveolar lavage fluid, and cytokine profiles of spleen
      cells were assessed. Compared to OVA-induced hallmarks of asthma, oral
      administration of zerumbone induced lower OVA-specific immunoglobulin E (IgE) and
      higher IgG2a antibody production, attenuated airway hyperresponsiveness,
      prevented eosinophilic pulmonary infiltration, and ameliorated mucus
      hypersecretion. Zerumbone treatment also reduced the production of eotaxin,
      keratinocyte-derived chemokine (KC), interleukin (IL)-4, IL-5, IL-10, and IL-13,
      and promoted Th1 cytokine interferon (IFN)-gamma production in asthmatic mice.
      Taken together, these results suggest that zerumbone exhibits an antiallergic
      effect via modulation of Th1/Th2 cytokines in an asthmatic mouse model. 

PMID- 25573404
TI  - Levo-1-methyl tryptophan aggravates the effects of mouse hepatitis virus (MHV
      A59) infection.
AB  - Mice infected with mouse hepatitis virus A59 (MHV-A59) develop autoantibodies
      (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH) with a
      concomitant enhancement of transaminases and release of alarmins such as uric
      acid and high-mobility group box protein 1 (HMGB1). Tryptophan catabolism is an
      endogenous mechanism that restricts excessive immune responses, thereby
      preventing immunopathology. Since indoleamine-2,3-dioxygenase (IDO) is the key
      and rate-limiting enzyme of tryptophan catabolism, the aim of this work was to
      explore whether specific inhibition of IDO by Levo-1-methyl tryptophan (MT) could
      affect MHV actions. Results showed that MT strongly enhanced the
      hypergammaglobulinemia induced by the virus, as well as anti-MHV Ab and uric acid
      release. Moreover, infected mice treated with MT did express anti-FAH autoAb and
      high levels of serum HMGB1. Survival of MHV-infected animals treated with MT was
      severely reduced compared with that of MHV-infected mice or controls only treated
      with MT. Furthermore, histological liver examination indicated that MT induced
      fibrosis in MHV-infected animals, whereas MT itself increased uric acid levels
      without shortening the animal life Thus, under our experimental conditions,
      results indicated an exacerbated response to MHV infection when IDO was blocked
      by MT. 

PMID- 25573405
TI  - Neuraminidase inhibitors, superinfection and corticosteroids affect survival of
      influenza patients.
AB  - We aimed to study factors influencing outcomes of adults hospitalised for
      seasonal and pandemic influenza.  Individual-patient data from three Asian
      cohorts (Hong Kong, Singapore and Beijing; N=2649) were analysed. Adults
      hospitalised for laboratory-confirmed influenza (prospectively diagnosed) during
      2008-2011 were studied. The primary outcome measure was 30-day survival.
      Multivariate Cox regression models (time-fixed and time-dependent) were used.
      Patients had high morbidity (respiratory/nonrespiratory complications in 68.4%,
      respiratory failure in 48.6%, pneumonia in 40.8% and bacterial superinfections in
      10.8%) and mortality (5.9% at 30 days and 6.9% at 60 days). 75.2% received
      neuraminidase inhibitors (NAI) (73.8% received oseltamivir and 1.4% received
      peramivir/zanamivir; 44.5% of patients received NAI <=2 days and 65.5% <=5 days
      after onset of illness); 23.1% received systemic corticosteroids. There were
      fewer deaths among NAI-treated patients (5.3% versus 7.6%; p=0.032). NAI
      treatment was independently associated with survival (adjusted hazard ratio (HR)
      0.28, 95% CI 0.19-0.43), adjusted for treatment-propensity score and patient
      characteristics. Superinfections increased (adjusted HR 2.18, 95% CI 1.52-3.11)
      and chronic statin use decreased (adjusted HR 0.44, 95% CI 0.23-0.84) death
      risks. Best survival was shown when treatment started within <=2 days (adjusted
      HR 0.20, 95% CI 0.12-0.32), but there was benefit with treatment within 3-5 days
      (adjusted HR 0.35, 95% CI 0.21-0.58). Time-dependent analysis showed consistent
      results of NAI treatment (adjusted HR 0.39, 95% CI 0.27-0.57). Corticosteroids
      increased superinfection (9.7% versus 2.7%) and deaths when controlled for
      indications (adjusted HR 1.73, 95% CI 1.14-2.62). Early NAI treatment was
      associated with shorter length of stay in a subanalysis. NAI treatment may
      improve survival of hospitalised influenza patients; benefit is greatest from,
      but not limited to, treatment started within 2 days of illness. Superinfections
      and corticosteroids increase mortality. Antiviral and non-antiviral management
      strategies should be considered. 

PMID- 25573406
TI  - Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD
      (GOLD 2-4).
AB  - Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC)
      compared with the mono-components was evaluated in patients with moderate to very
      severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised,
      double-blind, parallel-group, multicentre, phase III trials. Patients received
      tiotropium+olodaterol FDC 2.5/5 MUg or 5/5 MUg, tiotropium 2.5 MUg or 5 MUg, or
      olodaterol 5 MUg delivered once-daily via Respimat inhaler over 52 weeks. Primary
      end points were forced expiratory volume in 1 s (FEV1) area under the curve from
      0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory
      Questionnaire (SGRQ) total score at 24 weeks. In total, 5162 patients (2624 in
      Study 1237.5 and 2538 in Study 1237.6) received treatment. Both FDCs
      significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono
      components in both studies. Statistically significant improvements in SGRQ total
      score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5
      MUg. Incidence of adverse events was comparable between the FDCs and the mono
      components. These studies demonstrated significant improvements in lung function
      and health-related quality of life with once-daily tiotropium+olodaterol FDC
      versus mono-components over 1 year in patients with moderate to very severe COPD.

PMID- 25573408
TI  - Radial endobronchial ultrasound images for ground-glass opacity pulmonary
      lesions.
AB  - Radial endobronchial ultrasound (R-EBUS) is a useful tool for precise
      localisation of peripheral pulmonary lesions, but there have been no detailed
      reports about the use of R-EBUS images for ground-glass opacity (GGO). The R-EBUS
      images of 116 patients with GGO, who were diagnosed as having adenocarcinoma by R
      EBUS with a guide sheath (EBUS-GS), were compared with the respective chest
      computed tomography findings. In 103 patients, R-EBUS images were correlated with
      the histological surgical specimens. R-EBUS images of GGO were identified based
      on the internal structure of the lesion and classified into two groups. Blizzard
      showed an enlarged, diffuse hyperintense acoustic shadow. Mixed blizzard showed a
      combination of blizzard and some diffuse heterogeneity with several hyperechoic
      dots and vessels. All pure GGO lesions (nine out of nine) were blizzard on R
      EBUS. For part-solid GGOs, the percentage of mixed blizzard was inversely related
      to the amount of the GGO component. Histological findings from surgery revealed
      that all blizzard lesions were on the spectrum of adenocarcinoma in situ to well
      differentiated adenocarcinoma while majority (33 out of 64) of mixed blizzard
      lesions were moderately to poorly differentiated adenocarcinoma. R-EBUS types are
      important to locate GGOs prior to transbronchial sampling with EBUS-GS. 

PMID- 25573407
TI  - Obesity as a susceptibility factor to indoor particulate matter health effects in
      COPD.
AB  - Our goal was to investigate whether obesity increases susceptibility to the
      adverse effects of indoor particulate matter on respiratory morbidity among
      individuals with chronic obstructive pulmonary disease (COPD). Participants with
      COPD were studied at baseline, 3 and 6 months. Obesity was defined as a body mass
      index >=30 kg.m(-2). At each time point, indoor air was sampled for 5-7 days and
      particulate matter (PM) with an aerodynamic size <=2.5 MUm (PM2.5) and 2.5-10 MUm
      (PM2.5-10) was measured. Respiratory symptoms, health status, rescue medication
      use, exacerbations, blood biomarkers and exhaled nitric oxide were assessed
      simultaneously. Of the 84 participants enrolled, 56% were obese and all were
      former smokers with moderate-to-severe COPD. Obese participants tended to have
      less severe disease as assessed by Global Initiative for Chronic Obstructive
      Pulmonary Disease stage and fewer pack-years of smoking. There was evidence that
      obesity modified the effects of indoor PM on COPD respiratory outcomes. Increases
      in PM2.5 and PM2.5-10 were associated with greater increases in nocturnal
      symptoms, dyspnoea and rescue medication use among obese versus non-obese
      participants. The impact of indoor PM on exacerbations, respiratory status and
      wheeze also tended to be greater among obese versus non-obese participants, as
      were differences in airway and systemic inflammatory responses to indoor PM. We
      found evidence that obesity was associated with exaggerated responses to indoor
      fine and coarse PM exposure among individuals with COPD.

PMID- 25573409
TI  - Lung function in the children of immigrant and UK-born south-Asian mothers.

PMID- 25573411
TI  - Tandem catalytic oxidative deacetylation of acetoacetic esters and heteroaromatic
      cyclizations.
AB  - One pot syntheses of furan, thiophene, and pyrrole were accomplished by oxidative
      deacetylation using Mn(III)/Co(II) catalysts and the Paal-Knorr reaction from 1,5
      dicarbonyl compounds, which are prepared from the conjugate addition of ethyl
      acetoacetate to alpha,beta-unsaturated carbonyl compounds. The oxidative
      deacetylation and reductive cyclization of beta-ketoesters derived from ethyl
      acetoacetate and o-nitrobenzyl bromides efficiently produced diversely
      substituted indoles.

PMID- 25573410
TI  - Effect of obstructive sleep apnoea on severity and short-term prognosis of acute
      coronary syndrome.
AB  - The goal of this study was to evaluate the influence of obstructive sleep apnoea
      on the severity and short-term prognosis of patients admitted for acute coronary
      syndrome. Obstructive sleep apnoea was defined as an apnoea-hypopnoea index (AHI)
      >15 h(-1). We evaluated the acute coronary syndrome severity (ejection fraction,
      Killip class, number of diseased vessels, and plasma peak troponin) and short
      term prognosis (length of hospitalisation, complications and mortality). We
      included 213 patients with obstructive sleep apnoea (mean+/-sd AHI 30+/-14 h(-1),
      61+/-10 years, 80% males) and 218 controls (AHI 6+/-4 h(-1), 57+/-12 years, 82%
      males). Patients with obstructive sleep apnoea exhibited a higher prevalence of
      systemic hypertension (55% versus 37%, p<0.001), higher body mass index (29+/-4
      kg.m(-2) versus 26+/-4 kg.m(-2), p<0.001), and lower percentage of smokers (61%
      versus 71%, p=0.04). After adjusting for smoking, age, body mass index and
      hypertension, the plasma peak troponin levels were significantly elevated in the
      obstructive sleep apnoea group (831+/-908 ng.L(-1) versus 987+/-884 ng.L(-1),
      p=0.03) and higher AHI severity was associated with an increased number of
      diseased vessels (p=0.04). The mean length of stay in the coronary care unit was
      higher in the obstructive sleep apnoea group (p=0.03). This study indicates that
      obstructive sleep apnoea is related to an increase in the peak plasma troponin
      levels, number of diseased vessels, and length of stay in the coronary care unit.

PMID- 25573413
TI  - Hypoxia-mediated immune evasion of pancreatic carcinoma cells.
AB  - Hypoxia is one of the characteristics of human and animal tumors. To investigate
      the association between hypoxia and the immune evasion of cancer cells, the
      present study examined paraffin sections of pancreatic tissues from patients with
      pancreatic carcinoma, chronic pancreatitis and normal pancreatic tissue and
      established a series of PANC-1 cell lines, which were cultured under various
      hypoxic and normoxic conditions. The results demonstrated that the expression of
      hypoxia-inducible 1alpha (HIF-1alpha) in pancreatic carcinoma was significantly
      higher compared with that in the chronic pancreatitis and normal pancreatic
      tissues, which revealed that a hypoxic microenvironment existed in pancreatic
      carcinoma. HIF-1alpha was inversely correlated with major histocompatibility
      complex class I chain-related (MIC) genes, which indicated that hypoxia was
      involved in tumor immune evasion. The cell experiments demonstrated that the
      mechanism involved shedding of the MIC from the membrane of the pancreatic
      carcinoma cells, which then formed soluble (s)MIC. The sMIC genes downregulated
      natural killer (NK) group 2, member D and the cytotoxic activity of NK cells.
      Depending on its activity, the nitric oxide-cyclic guanosine monophosphate
      protein kinase G signaling pathway can either increase or inhibit immune evasion
      of pancreatic cancer cells.

PMID- 25573412
TI  - Kinesin superfamily protein 17 contributes to the development of bone cancer pain
      by participating in NR2B transport in the spinal cord of mice.
AB  - Taureatment of bone cancer pain remains a challenge, while the mechanisms causing
      the pain remain elusive. We demonstrated that the expression of the N-methyl-D
      aspartate (NMDA) receptor NR2B subunit was upregulated in mice with bone cancer
      pain. Kinesin superfamily protein 17 (KIF17), a recently characterized member of
      the kinesin superfamily proteins, has been demonstrated to transport and deliver
      the NR2B subunit to dendrites in mammalian neurons. In the present study, we
      induced bone cancer pain via femur bone cavity osteosarcoma NCTC 2472 tumor cell
      implantation (TCI) in mice. The results showed that TCI in mice increased the
      number of spontaneous flinches, mechanical allodynia events, expression of spinal
      KIF17 and NR2B subunits. Intrathecal administration of KIF17 antisense
      oligodeoxynucleotide (ODN) attenuated the behavioral signs of bone cancer pain
      and suppressed the increased expression of NR2B induced by TCI. In addition,
      KIF17 binds to a protein complex that contains mLin-10 to transport NR2B, and we
      determined that the increase of mLin-10 was suppressed following admini-stration.
      Thus, these findings suggested that KIF17 contributed to the development of bone
      cancer pain in the spinal cord through NR2B transport and that mLin-10 may also
      play a role in pain development.

PMID- 25573414
TI  - Ratiometric fluorescence imaging of cellular polarity: decrease in mitochondrial
      polarity in cancer cells.
AB  - Mitochondrial polarity strongly influences the intracellular transportation of
      proteins and interactions between biomacromolecules. The first fluorescent probe
      capable of the ratiometric imaging of mitochondrial polarity is reported. The
      probe, termed BOB, has two absorption maxima (lambdaabs = 426 and 561 nm) and two
      emission maxima--a strong green emission (lambdaem = 467 nm) and a weak red
      emission (642 nm in methanol)--when excited at 405 nm. However, only the green
      emission is markedly sensitive to polarity changes, thus providing a ratiometric
      fluorescence response with a good linear relationship in both extensive and
      narrow ranges of solution polarity. BOB possesses high specificity to
      mitochondria (Rr =0.96) that is independent of the mitochondrial membrane
      potential. The mitochondrial polarity in cancer cells was found to be lower than
      that of normal cells by ratiometric fluorescence imaging with BOB. The difference
      in mitochondrial polarity might be used to distinguish cancer cells from normal
      cells.

PMID- 25573415
TI  - Red blood cell storage duration and trauma.
AB  - Numerous retrospective clinical studies suggest that transfusion of longer stored
      red blood cells (RBCs) is associated with an independent risk of poorer outcomes
      for certain groups of patients, including trauma, intensive care, and cardiac
      surgery patients. Large multicenter randomized controlled trials are currently
      underway to address the concern about RBC storage duration. However, none of
      these randomized controlled trials focus specifically on trauma patients with
      hemorrhage. Major trauma, particularly due to road accidents, is the leading
      cause of critical injury in the younger-than-40-year-old age group. Severe
      bleeding associated with major trauma induces hemodynamic dysregulation that
      increases the risk of hypoxia, coagulopathy, and potentially multiorgan failure,
      which can be fatal. In major trauma, a multitude of stress-associated changes
      occur to the patient's RBCs, including morphological changes that increase cell
      rigidity and thereby alter blood flow hemodynamics, particularly in the
      microvascular vessels, and reduce RBC survival. Initial inflammatory responses
      induce deleterious cellular interactions, including endothelial activation, RBC
      adhesion, and erythrophagocytosis that are quickly followed by profound
      immunosuppressive responses. Stored RBCs exhibit similar biophysical
      characteristics to those of trauma-stressed RBCs. Whether transfusion of RBCs
      that exhibit storage lesion changes exacerbates the hemodynamic perturbations
      already active in the trauma patient is not known. This article reviews findings
      from several recent nonrandomized studies examining RBC storage duration and
      clinical outcomes in trauma patients. The rationale for further research on RBC
      storage duration in the trauma setting is provided. 

PMID- 25573416
TI  - Blood component use in a sub-Saharan African country: results of a 4-year
      evaluation of diagnoses associated with transfusion orders in Namibia.
AB  - National blood use patterns in sub-Saharan Africa are poorly described. Although
      malaria and maternal hemorrhage remain important drivers of blood demand across
      Africa, economic growth and changes in malaria, HIV/AIDS, and noncommunicable
      disease epidemiology may contribute to changes in blood demand. We evaluated
      indications for blood use in Namibia, a country in southern Africa, using a
      nationally representative sample and discuss implications for the region.
      Clinical and demographic data related to the issuance of blood component units in
      Namibia were reviewed for a 4-year period (August 1, 2007-July 31, 2011).
      Variables included blood component type, recipient age and sex, and diagnosis.
      Diagnoses reported by clinicians were reclassified into International Statistical
      Classification of Diseases, 10th Revision categories. Multiple imputation methods
      were used to complete a data set missing age, sex or diagnosis data. Descriptive
      analyses were conducted to describe indications for transfusions and use of red
      blood cells (RBCs), platelets, and plasma. A total of 39,313 records accounting
      for 91,207 blood component units were analyzed. The median age of Namibian
      transfusion recipients was 45 years (SD, +/-19). A total of 78,660 RBC units were
      issued in Namibia during the study period. Red blood cells transfused for
      "unspecified anemia" accounted for the single largest category of blood issued
      (24,798 units). Of the overall total, 38.9% were for diseases of the blood and
      blood-forming organs (D50-D89). Infectious disease (A00-B99), pregnancy (O00
      O99), and gastrointestinal (K20-K93) accounted for 14.8%, 11.1%, and 6.1% of RBC
      units issued, respectively. Although a specific diagnosis of malaria accounted
      for only 2.7% of pediatric transfusions, an unknown number of additional
      transfusions for malaria may have been categorized by requesting physicians as
      unspecified anemia and counted under diseases of blood forming organs. During the
      study period, 9751 units of fresh-frozen plasma were issued. Nearly one-quarter
      of these units (23.1%) were issued for gastrointestinal (K20-K93) diagnoses.
      Malignant neoplasms (C00-C97) accounted for 38.1% of 2978 platelet units issued.
      Blood use in Namibia reflects changes in the health care system due to economic
      development, improvement in HIV/AIDS and malaria epidemiology, high rates of
      health care facility-based childbirth, and access to noncommunicable disease
      treatment. However, better documentation of the indications for transfusion is
      needed to confirm these observations. Changing patterns of health care will
      result in changing demands for blood components. Improved methods to evaluate
      blood use patterns in sub-Saharan Africa may help set realistic national blood
      collection goals.

PMID- 25573417
TI  - A 52-year-old man with heartburn and weight loss.

PMID- 25573418
TI  - Aetiopathogenesis of functional dyspepsia.

PMID- 25573419
TI  - Positive expiratory pressure - Common clinical applications and physiological
      effects.
AB  - Breathing out against resistance, in order to achieve positive expiratory
      pressure (PEP), is applied by many patient groups. Pursed lips breathing and a
      variety of devices can be used to create the resistance giving the increased
      expiratory pressure. Effects on pulmonary outcomes have been discussed in several
      publications, but the expected underlying physiology of the effect is seldom
      discussed. The aim of this article is to describe the purpose, performance,
      clinical application and underlying physiology of PEP when it is used to increase
      lung volumes, decrease hyperinflation or improve airway clearance. In clinical
      practice, the instruction how to use an expiratory resistance is of major
      importance since it varies. Different breathing patterns during PEP increase or
      reduce expiratory flow, result in movement of EPP centrally or peripherally and
      can increase or decrease lung volume. It is therefore necessary to give the right
      instructions to obtain the desired effects. As the different PEP techniques are
      being used by diverse patient groups it is not possible to give standard
      instructions. Based on the information given in this article the instructions
      have to be adjusted to give the optimal effect. There is no consensus regarding
      optimal treatment frequency and number of cycles included in each treatment
      session and must also be individualized. In future research, more precise
      descriptions are needed about physiological aims and specific instructions of how
      the treatments have been performed to assure as good treatment quality as
      possible and to be able to evaluate and compare treatment effects. 

PMID- 25573420
TI  - Comparisons of guardianship laws and surrogate decision-making practices in
      China, Japan, Thailand and Australia: a review by the Asia Consortium,
      International Psychogeriatric Association (IPA) capacity taskforce.
AB  - BACKGROUND: The International Psychogeriatric Association (IPA) capacity
      taskforce was established to promote the autonomy, proper access to care, and
      dignity of persons with decision-making disabilities (DMDs) across nations. The
      Asia Consortium of the taskforce was established to pursue these goals in the
      Asia-Pacific region. This paper is part of the Asia Consortium's initiative to
      promote understanding and advocacy in regard to surrogate decision-making across
      the region. METHOD: The current guardianship laws are compared, and
      jurisdictional variations in the processes for proxy decision-making to support
      persons with DMDs and other health and social needs in China, Japan, Thailand,
      and Australia are explored. RESULTS: The different Asia-Pacific countries have
      various proxy decision-making mechanisms in place for persons with DMDs, which
      are both formalized according to common law, civil law, and other legislation,
      and shaped by cultural practices. Various processes for guardianship and
      mechanisms for medical decision-making and asset management exist across the
      region. Processes that are still evolving across the region include those that
      facilitate advanced planning as a result of the paucity of legal structures for
      enduring powers of attorney (EPA) and guardianship in some regions, and the
      struggle to achieve consensual positions in regard to end-of-life decision
      making. Formal processes for supporting decision-making are yet to be developed.
      CONCLUSIONS: The diverse legal approaches to guardianship and administration must
      be understood to meet the challenges of the rapidly ageing population in the Asia
      Pacific region. Commonalities in the solutions and difficulties faced in
      encountering these challenges have global significance.

PMID- 25573421
TI  - Effects of age and sex on the single-dose pharmacokinetics and pharmacodynamics
      of apixaban.
AB  - BACKGROUND AND OBJECTIVES: The effects of age and sex on apixaban
      pharmacokinetics and pharmacodynamics were studied. METHODS: This was an open
      label, single-dose, 2 * 2 factorial study. Healthy young (aged 18-40 years) and
      elderly (aged >= 65 years) male and female subjects received a single oral 20 mg
      dose of apixaban. Blood and urine samples were collected for pharmacokinetic and
      pharmacodynamic (blood only) analyses. Subjects were monitored for adverse events
      throughout the study. RESULTS: Seventy-nine subjects were enrolled into four
      groups: young males (n = 20), elderly males (n = 20), young females (n = 20) and
      elderly females (n = 19). Age did not affect the maximum observed plasma
      concentration (C max). The mean area under the concentration-time curve from time
      zero extrapolated to infinite time (AUCinfinity) was 32% greater in elderly
      subjects than in young subjects. The mean C max and AUCinfinity values were 18
      and 15% higher, respectively, in females than in males. The time course of the
      mean international normalized ratio (INR), modified prothrombin time (mPT) and
      anti-Xa activity tracked the apixaban concentration-time curve. All three
      pharmacodynamic measures exhibited a positive linear correlation with the plasma
      apixaban concentration. Differences in the mean INR, mPT and anti-Xa activity
      between age and sex groups were small (<15% at the maximum mean values) and were
      generally related to pharmacokinetic differences. However, anti-Xa activity
      demonstrated less variability than the INR or mPT, and may have utility as a
      bioassay for apixaban. Apixaban was well tolerated, with no serious adverse
      events. CONCLUSION: There were no clinically meaningful age- or sex-related
      differences in the pharmacokinetics and pharmacodynamics of apixaban that would
      require dose modification on the basis of age or sex alone.

PMID- 25573422
TI  - Decreased deformability of lymphocytes in chronic lymphocytic leukemia.
AB  - This paper reports the first study of stiffness/deformability changes of
      lymphocytes in chronic lymphocytic leukemia (CLL) patients, demonstrating that at
      the single cell level, leukemic metastasis progresses are accompanied by
      biophysical property alterations. A microfluidic device was utilized to
      electrically measure cell volume and transit time of single lymphocytes from
      healthy and CLL patients. The results from testing thousands of cells reveal that
      lymphocytes from CLL patients have higher stiffness (i.e., lower deformability),
      as compared to lymphocytes in healthy samples, which was also confirmed by AFM
      indentation tests. This observation is in sharp contrast to the known knowledge
      on other types of metastatic cells (e.g., breast and lung cancer cells) whose
      stiffness becomes lower as metastasis progresses. 

PMID- 25573423
TI  - Effect of ACE inhibitors and AT1 receptor antagonists on pentylenetetrazole
      induced convulsions in mice.
AB  - Experimental data show that some angiotensin-converting enzyme (ACE) inhibitors
      and angiotensin AT(1) receptor antagonists that are normally used as
      antihypertensive drugs can exert anticonvulsant-like activity against audiogenic
      seizures. In the current study, a number of ACE inhibitors (captopril, enalapril,
      cilazapril, perindopril and zofenopril) and AT(1) antagonists (losartan,
      telmisartan and candesartan) were examined against pentylenetetrazole (PTZ)
      induced seizures in mice. Captopril (50 mg/kg) administered intraperitoneally
      significantly raised the PTZ threshold (p < 0.05). The remaining drugs were not
      protective against PTZ-induced convulsions. The current study indicates that
      captopril decreases PTZ-evoked seizures in mice, which is an animal model of
      myoclonic convulsions.

PMID- 25573424
TI  - Ischaemic stroke with partial haemorrhagic transformation related to a small
      sized tuberculum sellae meningioma.

PMID- 25573426
TI  - Directed assembly of vesicle-templated polymer nanocapsules under near
      physiological conditions.
AB  - This work addresses the challenge of creating hollow polymer capsules with wall
      thickness in the single-nanometer range under mild conditions. We present a
      simple and scalable method for the synthesis of hollow polymer nanocapsules in
      the bilayers of spontaneously assembled surfactant vesicles. Polymerization is
      initiated thermally with the help of a peroxide initiator and an amine activator
      codissolved with monomers and cross-linkers in the hydrophobic interior of the
      surfactant bilayer. To avoid premature polymerization, the initiator and the
      activator were added separately to the mixtures of cetyltrimethylammonium
      tosylate (CTAT) and sodium dodecylbenzenesulfonate (SDBS) containing monomers and
      cross-linkers. Upon hydration and mixing of the aqueous solutions, equilibrium
      monomer-loaded vesicles formed spontaneously after a brief incubation. The
      removal of oxygen and further incubation at slightly elevated temperatures (35-40
      degrees C) for 1 to 2 h has led to the formation of hollow polymer nanocapsules.
      Structural and permeability characterization supported the high yield of
      nanocapsules with no pinhole defects. 

PMID- 25573425
TI  - Comparison of sorafenib-loaded poly (lactic/glycolic) acid and DPPC liposome
      nanoparticles in the in vitro treatment of renal cell carcinoma.
AB  - The objective of this study is to develop and compare several Sorafenib-loaded
      biocompatible nanoparticle models in order to optimize drug delivery and tumor
      cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy.
      Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan
      (HMC)-coated DPPC liposomes were evaluated for several characteristics including
      zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials
      were also studied using cell line RCC 786-0, a human metastatic clear cell
      histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC
      coated DPPC liposomes exhibited significantly improved cell kill compared to
      Sorafenib alone at lower concentrations, namely 10-15 and 5-15 MUM from 24 to 96
      h, respectively. At maximum dosage and time (15 MUM and 96 h), Sorafenib-loaded
      PLGA and HMC-coated liposomes killed 88.3 +/- 1.8% and 98 +/- 1.1% of all tumor
      cells, significant values compared with Sorafenib 81.8 +/- 1.7% (p < 0.01).
      Likewise, HMC coating substantially improved cell kill for liposome model for all
      concentrations (5-15 MUM) and at time points (24-96 h) (p < 0.01). PLGA and HMC
      coated liposomes are promising platforms for drug delivery of Sorafenib. Because
      of different particle characteristics of PLGA and liposomes, each model can be
      further developed for unique clinical modalities.

PMID- 25573427
TI  - Positive side effects of Ca antagonists for osteoarthritic joints-results of an
      in vivo pilot study.
AB  - BACKGROUND: We have shown previously that some calcium antagonists inhibit
      hyaluronan export, loss of proteoglycans, and degradation of collagen from
      osteoarthritic cartilage. Clinically approved calcium antagonists normally are
      prescribed for cardiac arrhythmia. In the present study, we compared the effect
      of these drugs on osteoarthritic patients which had received no medication and
      patients which were also diagnosed for cardiac arrhythmias and were treated with
      calcium antagonists. The effects and the side effects of the used drugs were
      analyzed. METHOD: We used the Lequesne questionnaire to examine patients with
      osteoarthritis (212 patients, control group receiving no calcium antagonists) and
      patients with cardiac arrhythmia and osteoarthritis (188 patients treated with
      various calcium antagonists). The answers of the questionnaires were transformed
      into the Lequesne scoring system quantifying the severity of the disease. The
      Lequesne score is a standardized questionnaire focused on osteoarthritis. It is a
      24-scale questionary in which low scores indicate low functional activity.
      RESULTS: The data showed that the mean score of the control group (6.2) was
      higher than the treated group (5.2), the drugs differed in their efficiency.
      Verapamil had a slightly worse score and Azupamil, Escor, Felodipine, and
      Nifedipine showed no alteration. Adalat, Amlodipine, Carmen, Nitrendipin, and
      Norvasc lead to an improvement. CONCLUSION: These results suggest that inhibition
      of hyaluronan export may have a beneficial effect on human osteoarthritis.

PMID- 25573428
TI  - Predictive model of oral cancer metastasis for different cancer sites and age
      groups.
AB  - AIM: The high incidence rates for oral cancer (excluding lip) are especially
      found in the South and South-East Asia. Therefore, the aim of the present study
      was to investigate the relationship between sex, age, site, and metastasis of a
      large sample with oral squamous cell carcinoma (OSCC). METHODS: A total of 989
      OSCC treated with neck dissection were selected. All the relevant data were
      recorded from biopsy request forms. The patients were divided into seven groups,
      and there were nine different oral sites. RESULTS: The male-to-female ratio of
      the sample was 4:1. Most of the patients were aged between 30 and 60 years. Of
      the 989 patients, approximately 40% patients had metastasis. Age <30 years showed
      a higher probability of metastasis compared to higher age groups, but it was not
      statistically significant. Palate cancers had more than 14 times higher chance of
      metastasis, followed by maxilla (4.6 times) and tongue (2.8 times). CONCLUSION:
      The present study provides important information on the metastatic potential of
      OSCC in different oral sites, and identifies high-risk age groups for metastasis.
      This will be helpful in planning neck treatment for OSCC.

PMID- 25573429
TI  - A role for adaptor protein complex 1 in protein targeting to rhoptry organelles
      in Plasmodium falciparum.
AB  - The human malaria parasite Plasmodium falciparum possesses sophisticated systems
      of protein secretion to modulate host cell invasion and remodeling. In the
      present study, we provide insights into the function of the AP-1 complex in P.
      falciparum. We utilized GFP fusion constructs for live cell imaging, as well as
      fixed parasites in immunofluorescence analysis, to study adaptor protein mu1
      (PfMU1) mediated protein trafficking in P. falciparum. In trophozoites PfMU1
      showed similar dynamic localization to that of several Golgi/ER markers,
      indicating Golgi/ER localization. Treatment of transgenic parasites with
      Brefeldin A altered the localization of Golgi-associated PfMU1, supporting the
      localization studies. Co-localization studies showed considerable overlap of
      PfMU1 with the resident rhoptry proteins, rhoptry associated protein 1 (RAP1) and
      Cytoadherence linked asexual gene 3.1 (Clag3.1) in schizont stage.
      Immunoprecipitation experiments with PfMU1 and PfRAP1 revealed an interaction,
      which may be mediated through an intermediate transmembrane cargo receptor. A
      specific role for PfMU1 in trafficking was suggested by treatment with AlF4,
      which resulted in a shift to a predominantly ER-associated compartment and
      consequent decrease in co-localization with the Golgi marker GRASP. Together,
      these results suggest a role for the AP-1 complex in rhoptry protein trafficking
      in P. falciparum. 

PMID- 25573430
TI  - Reticulon protein-1C is a key component of MAMs.
AB  - The endoplasmic reticulum (ER) is a key organelle fundamental for the maintenance
      of cellular homeostasis and the determination of cell fate under stress
      conditions. Reticulon-1C (RTN-1C) is a member of the reticulon family proteins
      localized primarily on the ER membrane and known to regulate ER structure and
      function. Several cellular processes depend on the structural and functional
      crosstalk between different organelles, particularly on the endoplasmic reticulum
      and mitochondria. These dynamic contacts, called mitochondria-associated ER
      membranes (MAMs), are essential for the maintenance of mitochondrial structure
      and participate in lipid and calcium exchanges between the two organelles. In
      this study we investigated the impact of RTN-1C modulation on mitochondrial
      dynamics. We demonstrate that RTN-1C controls mitochondrial structure and
      function affecting intracellular Ca2+ homeostasis and lipid exchange between ER
      and mitochondria. We propose that these events depend on RTN-1C involvement in
      the regulation of ER-mitochondria cross-talk and define a role for RTN-1C in
      maintaining the function of contacts between the two organelles.

PMID- 25573431
TI  - Gene expression and fractionation resistance.
AB  - BACKGROUND: Previous work on whole genome doubling in plants established the
      importance of gene functional category in provoking or suppressing duplicate gene
      loss, or fractionation. Other studies, particularly in Paramecium have correlated
      levels of gene expression with vulnerability or resistance to duplicate loss.
      RESULTS: Here we analyze the simultaneous effect of function category and
      expression in two plant data sets, rosids and asterids. CONCLUSION: We
      demonstrate function category and expression level have independent effects,
      though expression does not play the dominant role it does in Paramecium.

PMID- 25573432
TI  - Two new macrosporin dimers from the fungus Alternaria sp. XZSBG-1.
AB  - Two new macrosporin dimers (1-2) along with four known compounds (3-6) were
      isolated from the extracts of the fungal strain Alternaria sp. XZSBG-1 from the
      sediment of the salt lake in the Bange, Tibetan, China. Their structures were
      determined by spectroscopic methods, mainly by 2D NMR spectra. Compounds 1 and 2
      are new macrosporin dimers with symmetric chemical structures. In the
      cytotoxicity assay and inhibited alpha-glucosidase activity assay, all these
      compounds showed no notable inhibitory activity. 

PMID- 25573433
TI  - Does insulin impact cold-induced fluid- and protein-extravasation?
AB  - BACKGROUND: Insulin has been shown to stabilize the endothelial barrier via
      inactivation of the endothelial contractile machinery and enhancement of cell
      cell adhesions. Here we explored if insulin by its endothelial-stabilizing and
      anti-inflammatory properties could influence the increase of fluid- and protein
      extravasation during hypothermia. METHODS: Two groups of animals (n=10, each)
      were cooled to 28 degrees C, with insulin-infusion (I-group) or without (C
      group), in a randomly controlled study. Fluid balance, hemodynamics, plasma
      volume (PV), colloid osmotic pressures in plasma (COPp) and interstitial fluid
      (COPi), hematocrit (Hct), cytokine profiles, serum-albumin- and protein
      concentrations were measured and fluid extravasation rate (FER) and albumin-and
      protein-masses calculated. RESULTS: During 240 min of hypothermia the albumin-
      and protein-masses together with COPp decreased significantly in both groups.
      COPi remained essentially unchanged. Plasma volume decreased significantly in the
      C-group, whereas only a decreasing trend was present in the I-group.
      Hemoconcentration was significant in both study groups reflected by the Hct
      values. A slight increasing trend of FER was seen in both groups from 0.10 (0.04)
      ml/kg/min and 0.09 (0.05) mg/kg/min, C-group and I-group, respectively, to 0.14
      (0.05) mg/kg/min and 0.12 (0.03) mg/kg/min, during the hypothermic period.
      Between-group differences were absent for all listed parameters including FER.
      CONCLUSION: Insulin administration does not impact fluid and protein
      extravasation significantly in animals undergoing cooling and prolonged
      hypothermia.

PMID- 25573434
TI  - NRC-interacting factor directs neurite outgrowth in an activity-dependent manner.
AB  - Nuclear hormone receptor coregulator-interacting factor 1 (NIF-1) is a zinc
      finger nuclear protein that was initially identified to enhance nuclear hormone
      receptor transcription via its interaction with nuclear hormone receptor
      coregulator (NRC). NIF-1 may regulate gene transcription either by modulating
      general transcriptional machinery or remodeling chromatin structure through
      interactions with specific protein partners. We previously reported that the
      cytoplasmic/nuclear localization of NIF-1 is regulated by the neuronal Cdk5
      activator p35, suggesting potential neuronal functions for NIF-1. The present
      study reveals that NIF-1 plays critical roles in regulating neuronal
      morphogenesis at early stages. NIF-1 was prominently expressed in the nuclei of
      developing rat cortical neurons. Knockdown of NIF-1 expression attenuated both
      neurite outgrowth in cultured cortical neurons and retinoic acid (RA)-treated
      Neuro-2a neuroblastoma cells. Furthermore, activity-induced Ca(2+) influx, which
      is critical for neuronal morphogenesis, stimulated the nuclear localization of
      NIF-1 in cortical neurons. Suppression of NIF-1 expression reduced the up
      regulation of neuronal activity-dependent gene transcription. These findings
      collectively suggest that NIF-1 directs neuronal morphogenesis during early
      developmental stages through modulating activity-dependent gene transcription. 

PMID- 25573436
TI  - Case of non-Herlitz junctional epidermolysis bullosa with COL17A1 mutation.

PMID- 25573437
TI  - Whey protein/polysaccharide-stabilized oil powders for topical application
      release and transdermal delivery of salicylic acid from oil powders compared to
      redispersed powders.
AB  - Oil-in-water (o/w) emulsions are commonly converted into solid-like powders in
      order to improve their physical and chemical stabilities. The aim of this study
      was to investigate whether whey protein/polysaccharide-stabilized o/w emulsions
      could be converted into stable oil powders by means of freeze-drying. Moreover,
      during this study, the effects of pH and polymer type on release and
      trans(dermal) delivery of salicylic acid, a model drug, from these oil powders
      were investigated and compared to those of the respective template emulsions and
      redispersed oil powders. Physical characterization of the various formulations
      was performed, such as droplet size analysis and oil leakage, and relationships
      drawn with regards to release and trans(dermal) delivery. The experimental
      outcomes revealed that the oil powders could be redispersed in water without
      changing the release characteristics of salicylic acid. pH and polymer type
      affected the release of salicylic acid from the oil powders, template emulsions,
      and redispersed powders similarly. Contrary, the transdermal delivery from the
      oil powders and from their respective redispersed oil powders was differently
      affected by pH and polymer type. It was hypothesized that the release had been
      influenced by the electrostatic interactions between salicylic acid and
      emulsifiers, whereas the transdermal performance could have been determined by
      the particle or aggregate sizes of the formulations. 

PMID- 25573435
TI  - Phosphatidylethanolamine-binding protein is not involved in u-opioid receptor
      mediated regulation of extracellular signal-regulated kinase.
AB  - Stimulation of the u-opioid receptor activates extracellular signal-regulated
      kinase (ERK), however, the mechanism by which this occurs remains to be
      elucidated. Phosphatidylethanolamine-binding protein (PEBP) has been reported to
      act as a negative regulator of the ERK cascade (Raf-MEK-ERK) by binding to Raf-1
      kinase. In the present study, the role of PEBP in u-opioid receptor-mediated ERK
      activation was investigated in Chinese hamster ovary/u cells and SH-SY5Y cells,
      as well as in human embryonic kidney 293 cells expressing other types of G
      protein-coupled receptors. The acute activation of u-opioid receptors by morphine
      or (D-Ala2, MePhe4, Gly5-ol) enkephalin induced a rapid activation of ERK.
      Prolonged morphine treatment did not affect the phosphorylation level of ERK
      compared with control cells, but the phosphorylation level of ERK decreased
      markedly when cells were precipitated with naloxone following chronic morphine
      treatment. For the phosphorylation of PEBP, no change was identified under the
      designated drug treatment and exposure duration. A total of two other types of G
      protein-coupled receptors, including Gs-coupled dopamine D1 receptors and Gq
      coupled adrenergic alpha1A receptors were also investigated and only the
      activation of adrenergic alpha1A receptors induced an upregulated phosphorylation
      of PEBP, which was protein kinase C activity dependent. Thus, PEBP did not have a
      significant role in u-opioid receptor-mediated regulation of ERK.

PMID- 25573438
TI  - Phytantriol-based in situ liquid crystals with long-term release for intra
      articular administration.
AB  - The purpose of this study was to develop an injectable in situ liquid crystal
      formulation for intra-articular (IA) administration, and in situ forming a
      viscous liquid crystalline gel with long-term release of sinomenine hydrochloride
      (SMH) upon water absorption. The pseudo-ternary phase diagram of phytantriol (PT)
      ethanol (ET)-water was constructed, and isotropic solutions were chosen for
      further optimization. The physicochemical properties of isotropic solutions were
      evaluated, and the phase structures of liquid crystalline gels formed by
      isotropic solutions in excess water were confirmed by crossed polarized light
      microscopy (CPLM) and small-angle X-ray scattering (SAXS). In vitro drug release
      studies were conducted by using a dialysis membrane diffusion method. The optimal
      in situ cubic liquid crystal (ISV2) (PT/ET/water, 64:16:20, w/w/w) loaded with 6
      mg/g of SMH showed a suitable pH, showed to be injectable, and formed a cubic
      liquid crystalline gel in situ with minimum water absorption within the shortest
      time. The optimal ISV2 was able to sustain the drug release for 6 days. An in
      situ hexagonal liquid crystal (ISH2) system was prepared by addition of 5%
      vitamin E acetate (VitEA) into PT in the optimal ISV2 system to improve the
      sustained release of SMH. This ISH2 (PT/VitEA/ET/water, 60.8:3.2:16:20, w/w/w/w)
      was an injectable isotropic solution with a suitable pH range. The developed ISH2
      was found to be able to sustain the drug release for more than 10 days and was
      suitable for IA injection for the treatment of rheumatoid arthritis (RA). 

PMID- 25573440
TI  - Comparison of skin color between two Asian populations: according to latitude and
      UV exposure.
AB  - BACKGROUND: Skin color varies among ethnic groups on accounts of genetic
      background. Within an ethnic group, skin color may also vary according to
      geographical environments and sun exposure habits. While many reports address
      skin color differences between ethnic groups, few have compared skin color within
      as ethnic group. AIMS: To compare skin color characteristics according to
      differences in latitude including UV exposure between two Asian populations
      (Korean and Cantonese [Chinese]). METHOD: We included 461 healthy female
      subjects: 317 Korean (age 42.3 +/- 7.16) and 144 Cantonese (age 41.5 +/- 11.2).
      Skin phototypes were classified according to the Fitzpatrick classification, and
      back skin color measured using the Minolta colorimeter. We evaluated the
      lightness (L*), yellowish (b*) value, individual typology angle (ITA degrees ),
      and minimal erythema dose (MED). RESULTS: Fitzpatrick phototype ratios were
      similar in Korean (II: 19.9%, III: 78.9%) and Cantonese (II: 27.1%, III: 72.9%).
      However, the L* (68.47 +/- 2.66 vs. 66.44 +/- 2.47), ITA degrees  (41.80 +/- 5.51
      vs. 40.20 +/- 5.79), and b* (20.56 +/- 1.71 vs. 19.28 +/- 1.97) were
      significantly higher in Korean than in Cantonese. Korean had a significant lower
      MED than Cantonese (22.33 +/- 2.89 vs. 23.38 +/- 6.04). CONCLUSIONS: Subjective
      phototype self-assessment showed similar results in Korean and Cantonese.
      However, objective skin color parameters differed between the two populations.
      Koreans, who live at a higher latitude and get relatively little sun exposure,
      have lighter skin color than the Cantonese and burn easily upon UV exposure.

PMID- 25573439
TI  - In vivo Toll-like receptor 5 (TLR5) imaging with radiolabeled anti-TLR5
      monoclonal antibody in rapamycin-treated mouse allogeneic skin transplantation
      model.
AB  - BACKGROUND: In organ transplantation, increasing evidence, both in experimental
      and human studies, indicates that Toll-like receptor (TLR) activation is involved
      in the innate immune recognition of allograft. TLR5, the only protein recognition
      receptor of TLRs, is indicated potentially to be the immune regulation target.
      This study was designed to determine whether TLR5 could be a biomarker for in
      vivo allograft visualization, after immunosuppressant rapamycin treatment, using
      radiolabeled sodium iodide ((131) I)-anti-TLR5 monoclonal antibody (mAb).
      METHODS: BALB/c mice were transplanted with C57BL/6 skin, with/without rapamycin
      treatment (the rapamycin-treated group and the phosphate buffered saline [PBS]
      rejection group, respectively). In vivo dynamic whole-body phosphor
      autoradiography and ex vivo biodistribution studies were conducted after (131) I
      anti-TLR5 mAb injection. RESULTS: Dynamic phosphor-autoradiography imaging showed
      clear graft localization from 12 h onward. At 72 h after injection, graft uptake
      quantified from images was higher for the rapamycin-treated group (26,448 +/- 904
      digital light units [DLU]/mm(2) ), compared with the PBS-treated allo-rejection
      group (9176 +/- 576 DLU/mm(2) ). Treatment with anti-TLR5 mAb inhibited graft
      uptake. Organ biodistribution study reflected the same tendency, and (131) I-anti
      TLR5 mAb uptake reached a maximum of 12.05 +/- 1.86 %ID/g (percent injected dose
      per gram) at 1 h, and graft-to-native skin ratio reached 8.10 +/- 0.10 %ID/g at
      72 h after injection in rapamycin-treated grafts. CONCLUSION: Radiolabeled anti
      TLR5 mAb showed higher uptake in allo-treated grafts compared with allo-rejection
      grafts, which was proved by non-invasive dynamic phosphor-autoradiography
      imaging, and invasive ex vivo biodistribution. Radiolabeled anti-TLR5 mAb is a
      new tracer for non-invasive in vivo imaging of TLR5 in rapamycin-treated
      allograft.

PMID- 25573441
TI  - Thrombolysis and expedited carotid revascularization.
AB  - With the move towards expedited carotid endarterectomy (CEA) in patients
      presenting with a transient ischemic attack/minor stroke and for offering
      intravenous thrombolysis <3 hours to patients with acute ischemic stroke, it is
      inevitable that surgeons will be asked to consider CEA in patients who have made
      a good recovery from their stroke after thrombolysis and who have a 50-99%
      internal carotid artery stenosis. The key question is: "how long after
      thrombolysis should I delay CEA to minimise the perioperative risk (especially
      intracranial hemorrhage [ICH]), whilst also minimizing the risks of further
      embolization and stroke?". Thirteen series have published outcomes in 361
      patients. Only a very small proportion of all thrombolysis patients (<5%) might
      be considered for expedited CEA and the majority underwent CEA <14 days (some <48
      hours). The 30-day death/stroke rate was 13/361 (3.6%), while the prevalence of
      ICH was 4/159 (2.5%). Most studies reported no increase in procedural risk if CEA
      was carried out soon after lysis, but one study questioned whether it was
      appropriate to perform CEA <72 hours because of an increased risk of ICH. The
      literature contains details of the complex effect that recombinant tissue
      plasminogen activator has on coagulation systems and on the integrity of the
      blood brain barrier, both of which will predispose towards ICH. The available
      literature suggests that CEA can be performed safely <14 days of lysis, but it is
      unclear whether surgery <72 hours is more dangerous. The key lesson for the
      surgeon is to adopt an aggressive policy regarding the treatment of post-CEA
      hypertension. 

PMID- 25573442
TI  - Carotid artery stenting: high-risk interventionist versus high-risk center.
AB  - Carotid artery stenting (CAS) is a less invasive alternative to carotid
      endarterectomy (CEA) for the management of carotid artery stenosis. Although
      early multicenter randomized controlled trials reported inferior results for CAS
      compared with CEA, recent advances in technology and increasing CAS operator
      expertise have lead to improved results. As with any procedure, a high caseload
      translates into increased experience and better outcomes. This article discusses
      the current shortfalls of CAS, as well as the various options available to
      improve CAS results. The majority of studies suggest that there is an inverse
      relationship between caseload volume and CAS outcomes that defines high-risk
      interventionists and high-risk centers. Centralizing CAS procedures to high
      volume centers is essential for optimization of CAS outcomes. 

PMID- 25573443
TI  - The pros and cons of endovascular and open surgical treatments for patients with
      acute limb ischemia.
AB  - The present review addresses the pros and cons of the current, wide variety of
      therapeutic options available for the treatment of acute limb ischemia (ALI).
      Despite five prospective randomized controlled trials comparing catheter directed
      thrombolysis and open surgical revascularization, no single treatment strategy
      can yet be considered optimal for patients with ALI. This report includes 20
      years of published data to evaluate the efficacy and safety profile of
      thrombolytic agents and adjunctive endovascular techniques when compared to open
      surgical revascularization. 

PMID- 25573444
TI  - Strategies to prevent spinal cord ischemia in thoracoabdominal aortic aneurysm
      repair.
AB  - Spinal cord ischemia (SCI) after thoracic and thoracoabdominal aortic aneurysm
      repair is a devastating complication, which happens after both open and
      endovascular repair. Incidence of SCI varies widely in the literature. Many
      factors during preoperative, operative and postoperative phases influence this
      incidence. The purpose of this article was to provide an overview on all factors
      influencing SCI and to report on the evidence in the literature about how to
      prevent SCI. 

PMID- 25573445
TI  - Outcomes following pacemaker implantation after transcatheter aortic valve
      implantation with CoreValve((r)) devices: Results from the FRANCE 2 Registry.
AB  - AIMS: Permanent pacemaker (PPM) implantation following high-degree
      atrioventricular block is frequently required after transcatheter aortic valve
      implantation (TAVI) using CoreValve((r)) . Recent improvement of the delivery
      system (CoreValve Accutrak((r)) ) aimed to ease delivery and reduce the PPM rate.
      Our study evaluated the incidences of PPM implantation following use of
      CoreValve((r)) or CoreValve Accutrak((r)) and the clinical outcome of these
      patients. METHODS AND RESULTS: A total of 883 patients (82 +/- 7 years; 41.3%
      female) with severe symptomatic aortic stenosis and self-expanding bioprosthesis
      implantation were included between January 2010 and October 2011 in 29 centers
      from the FRANCE 2 Registry. Follow-up data were available in 833 patients.
      CoreValve((r)) and CoreValve Accutrak((r)) were used in 343 (41.2%) and 490
      (58.8%) patients, respectively. During a mean follow-up of 242 +/- 179 days, all
      cause mortality was similar in patients with versus without PPM implantation
      (16.3 vs. 16.9%, P = 0.832).There was no significant difference in the PPM
      incidence in CoreValve((r)) and CoreValve Accutrak((r)) patients (30.4% vs.
      27.5%, P = 0.846). CONCLUSION: PPM implantation remained frequent after TAVI
      using CoreValve Accutrak((r)) . All-cause mortality was similar in patients with
      or without PPM implantation. The new device failed to show a significant decrease
      in PPM implantation incidence after TAVI. (c) 2015 Wiley Periodicals, Inc.

PMID- 25573447
TI  - Electronic couplings for molecular charge transfer: benchmarking CDFT, FODFT and
      FODFTB against high-level ab initio calculations. II.
AB  - A new database (HAB7-) of electronic coupling matrix elements (Hab) for electron
      transfer in seven medium-sized negatively charged pi-conjugated organic dimers is
      introduced. Reference data are obtained with spin-component scaled approximate
      coupled cluster method (SCS-CC2) and large basis sets. Assessed DFT-based
      approaches include constrained density functional theory (CDFT), fragment-orbital
      DFT (FODFT), self-consistent charge density functional tight-binding (FODFTB) and
      the recently described analytic overlap method (AOM). This complements the
      previously reported HAB11 database where only cationic dimers were considered.
      The CDFT method in combination with a functional based on PBE and including 50%
      of exact exchange (HFX) was found to provide best estimates, with a mean relative
      unsigned error (MRUE) of 8.2%. CDFT couplings systematically increase with
      decreasing fraction of HFX as a consequence of increasing delocalisation of the
      SOMO orbital. The FODFT method is found to be very robust underestimating
      electronic couplings by 28%. The FODFTB and AOM methods, although orders of
      magnitude more efficient in terms of computational effort than the DFT
      approaches, perform well with reasonably small errors of 54% and 29%,
      respectively, translating in errors in the non-adiabatic electron transfer rate
      of a factor of 2.4 and 1.7, respectively. We discuss carefully various sources of
      errors and the scope and limitations of all assessed methods taking into account
      the results obtained for both HAB7- and HAB11 databases. 

PMID- 25573446
TI  - [Determinants of utilization of emergency departments in Spain].

PMID- 25573448
TI  - Nanocolumnar coatings with selective behavior towards osteoblast and
      Staphylococcus aureus proliferation.
AB  - Bacterial colonization and biofilm formation on orthopedic implants is one of the
      worst scenarios in orthopedic surgery, in terms of both patient prognosis and
      healthcare costs. Tailoring the surfaces of implants at the nanoscale to actively
      promote bone bonding while avoiding bacterial colonization represents an
      interesting challenge to achieving better clinical outcomes. Herein, a Ti6Al4V
      alloy of medical grade has been coated with Ti nanostructures employing the
      glancing angle deposition technique by magnetron sputtering. The resulting
      surfaces have a high density of nanocolumnar structures, which exhibit strongly
      impaired bacterial adhesion that inhibits biofilm formation, while osteoblasts
      exhibit good cell response with similar behavior to the initial substrates. These
      results are discussed on the basis of a "lotus leaf effect" induced by the
      surface nanostructures and the different sizes and biological characteristics of
      osteoblasts and Staphylococcus aureus. 

PMID- 25573449
TI  - The learning curve of the three-port two-instrument complete thoracoscopic
      lobectomy for lung cancer-A feasible technique worthy of popularization.
AB  - BACKGROUND/OBJECTIVE: Cosmetic factors are important when considering minimally
      invasive surgery. For cosmetic improvement, a complete thoracoscopic lobectomy is
      accomplished via the three-port two-instrument (TPTI) technique. The resected
      specimen is removed without extending the port wounds. Only three wounds at 1.2
      cm are used to finish the procedure. METHODS: From June 2012 to December 2013, 60
      patients with lung cancer were to undergo lobectomy and complete mediastinal
      lymph node dissection via the TPTI technique without an accessory wound. The
      initial 28 cases (learning curve group) and the latest 28 cases were compared to
      assess the learning curve. RESULTS: Excluding four cases of conversion, there
      were 28 cases in each group. There were no differences between these two groups
      with respect to age, sex, tumor size, location of the lobectomy, mean blood loss,
      mean postoperative drainage time, and mean hospitalization time (p > 0.05). The
      mean surgery time significantly decreased, the mean number of lymph nodes removed
      significantly increased, and the postoperative stage was significantly more
      advanced in the latest 28 cases (p < 0.05). The conversion rate was similar in
      both groups. CONCLUSION: Three-port complete thoracoscopic lobectomy with the two
      instrument technique is feasible for lung cancer treatment. The length of the
      learning curve consisted of 28 cases. This TPTI technique should be popularized.

PMID- 25573452
TI  - Formation of disinfection byproducts in a recirculating mariculture system:
      emerging concerns.
AB  - Disinfection is commonly employed in recirculating mariculture systems (RMS) to
      control animal diseases and improve seawater quality; however, little is known
      about the occurrence of disinfection byproducts (DBPs) formed in such RMS.
      Beijing Aquarium is a typical RMS with artificially prepared seawater and mainly
      adopts a decentralized treatment strategy for different animal tanks, including
      sand filtration, foam fractionation, and disinfection (O3, UV, and O3/ClO2). This
      study reveals that the adopted disinfection processes were highly effective in
      controlling marine heterotrophic bacteria; however, some concerns were raised on
      the formation of various kinds of DBPs, including secondary oxidants, inorganic
      oxyanions, and hazardous organic species. Free chlorine and free bromine were
      generated from ozonation at health-relevant concentrations. High concentrations
      of BrO3(-) and ClO3(-) were formed in mammal tanks, which exceeded the USEPA
      regulated maximum contaminant level (MCL) for drinking water by 19-25 and 52-54
      times, respectively. Extremely high concentrations of NO3(-) were detected in
      mammal tanks, which considerably exceeded the MCL regulated by the Sea Water
      Quality Standard of China for the mariculture industry (Class II) by about 1100
      times. Undoubtedly, the presence of various DBPs poses serious health threats to
      aquarium animals. To solve these problems, potential control measures for DBPs
      are proposed. 

PMID- 25573450
TI  - Controlling ionotropic and metabotropic glutamate receptors with light:
      principles and potential.
AB  - Light offers unique advantages for studying and manipulating biomolecules and the
      cellular processes that they control. Optical control of ionotropic and
      metabotropic glutamate receptors has garnered significant interest, since these
      receptors are central to signaling at neuronal synapses and only optical
      approaches provide the spatial and temporal resolution required to directly probe
      receptor function in cells and tissue. Following the classical method of
      glutamate photo-uncaging, recently developed methods have added other forms of
      remote control, including those with high molecular specificity and genetic
      targeting. These tools open the door to the direct optical control of synaptic
      transmission and plasticity, as well as the probing of native receptor function
      in intact neural circuits. 

PMID- 25573453
TI  - Myocardial collagen deposition and inflammatory cell infiltration in cats with
      pre-clinical hypertrophic cardiomyopathy.
AB  - The histological features of feline hypertrophic cardiomyopathy (HCM) have been
      well documented, but there are no reports describing the histological features in
      mild pre-clinical disease, since cats are rarely screened for the disease in the
      early stages before clinical signs are apparent. Histological changes at the
      early stage of the disease in pre-clinical cats could contribute to an improved
      understanding of disease aetiology or progression. The aim of this study was to
      evaluate the histological features of HCM in the left ventricular (LV) myocardium
      of cats diagnosed with pre-clinical HCM. Clinically healthy cats with normal (n =
      11) and pre-clinical HCM (n = 6) were identified on the basis of
      echocardiography; LV free wall dimensions (LVFWd) and/or interventricular septal
      wall (IVSd) dimensions during diastole of 6-7 mm were defined as HCM, while
      equivalent dimensions <5.5 mm were defined as normal. LV myocardial sections were
      assessed and collagen content and inflammatory cell infiltrates were quantified
      objectively. Multifocal areas of inflammatory cell infiltration, predominantly
      lymphocytes, were observed frequently in the left myocardium of cats with pre
      clinical HCM. Tissue from cats with pre-clinical HCM also had a higher number of
      neutrophils and a greater collagen content than the myocardium of normal cats.
      The myocardium variably demonstrated other features characteristic of HCM,
      including arteriolar mural hypertrophy and interstitial fibrosis and, to a lesser
      extent, myocardial fibre disarray and cardiomyocyte hypertrophy. These results
      suggest that an inflammatory process could contribute to increased collagen
      content and the myocardial fibrosis known to be associated with HCM.

PMID- 25573454
TI  - Chitosan nanoparticle/PCL nanofiber composite for wound dressing and drug
      delivery.
AB  - Many investigations of wound dressings equipped with drug delivery systems have
      recently been conducted. Chitosan is widely used not only as a material for wound
      dressing by the efficacy of its own, but also as a nanoparticle for drug
      delivery. In this study, an electrospun polycaprolactone nanofiber composite with
      chitosan nanoparticles (ChiNP-PCLNF) was fabricated and then evaluated for its
      drug release and biocompatibility to skin fibroblasts. ChiNP-PCLNF complexes
      showed no cytotoxicity and nanoparticles adsorbed by van der Waals force were
      released into aquatic environments and then penetrated into rat primary
      fibroblasts. Our studies demonstrate the potential for application of ChiNP-PCLNF
      as a wound dressing system with drug delivery for skin wound healing without side
      effects. 

PMID- 25573455
TI  - Atrial fibrillation in young ischemic stroke patients: an underestimated cause?
AB  - BACKGROUND: Undetected atrial fibrillation (AF) is often suspected as the
      possible cause in patients with cryptogenic ischemic stroke (IS), especially in
      elderly population. In young IS patients, the prevalence of AF, particularly
      paroxysmal form, remains still not enough established. Our aim was to assess the
      presence of AF in young patients using a long-term electrocardiography (ECG)
      Holter monitoring. METHODS: The study set consisted of acute IS patients <=50
      years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship
      studY) study (NCT01541163). In all patients, admission ECG, serum cardiac
      markers, transesophageal echocardiography, 24-h and 3-week ECG Holter monitoring
      were performed. RESULTS: Out of 634 enrolled patients in the HISTORY study, 98
      were <=50 years (56 males, mean age 39.7 +/- 8.4). In total, AF was detected in
      10.2% of patients and 70% of them had a paroxysmal form of AF. The elevated serum
      cardiac markers were present in 70% of patients with detected AF (p = 0.0001).
      CONCLUSION: AF was detected in 10.2% of young stroke patients and paroxysmal form
      of AF prevailed. Using of long-term ECG Holter monitoring improved the detection
      of AF. Patients with presence of AF had more frequently elevated serum specific
      cardiac markers.

PMID- 25573457
TI  - Erratum to: Adjustable gastric banding and sleeve gastrectomy in Bardet-Biedl
      syndrome.

PMID- 25573456
TI  - 9-Phenanthrol inhibits recombinant and arterial myocyte TMEM16A channels.
AB  - BACKGROUND AND PURPOSE: In arterial smooth muscle cells (myocytes), intravascular
      pressure stimulates membrane depolarization and vasoconstriction (the myogenic
      response). Ion channels proposed to mediate pressure-induced depolarization
      include several transient receptor potential (TRP) channels, including TRPM4, and
      transmembrane protein 16A (TMEM16A), a Ca(2+) -activated Cl(-) channel (CaCC). 9
      Phenanthrol, a putative selective TRPM4 channel inhibitor, abolishes myogenic
      tone in cerebral arteries, suggesting that either TRPM4 is essential for pressure
      induced depolarization, upstream of activation of other ion channels or that 9
      phenanthrol is non-selective. Here, we tested the hypothesis that 9-phenanthrol
      is also a TMEM16A channel blocker, an ion channel for which few inhibitors have
      been identified. EXPERIMENTAL APPROACH: Patch clamp electrophysiology was used to
      measure rat cerebral artery myocyte and human recombinant TMEM16A (rTMEM16A)
      currents or currents generated by recombinant bestrophin-1, another Ca(2+) 
      activated Cl(-) channel, expressed in HEK293 cells. KEY RESULTS: 9-Phenanthrol
      blocked myocyte TMEM16A currents activated by either intracellular Ca(2+) or Eact
      , a TMEM16A channel activator. In contrast, 9-phenanthrol did not alter
      recombinant bestrophin-1 currents. 9-Phenanthrol reduced arterial myocyte TMEM16A
      currents with an IC50 of ~12 MUM. Cell-attached patch recordings indicated that 9
      phenanthrol reduced single rTMEM16A channel open probability and mean open time,
      and increased mean closed time without affecting the amplitude. CONCLUSIONS AND
      IMPLICATIONS: These data identify 9-phenanthrol as a novel TMEM16A channel
      blocker and provide an explanation for the previous observation that 9
      phenanthrol abolishes myogenic tone when both TRPM4 and TMEM16A channels
      contribute to this response. 9-Phenanthrol may be a promising candidate from
      which to develop TMEM16A channel-specific inhibitors.

PMID- 25573458
TI  - Ventilatory and Metabolic Response in the Incremental Shuttle and 6-Min Walking
      Tests Measured by Telemetry in Obese Patients Prior to Bariatric Surgery.
AB  - BACKGROUND: Low cardiopulmonary fitness, measured by oxygen uptake peak (VO 2pk),
      is associated with postoperative complications and mortality. Obese people have
      difficulty in performing the cardiopulmonary exercise test, which requires
      maximal exertion. The incremental shuttle walking test (ISWT) and 6-min walking
      test (6MWT) have been used to assess cardiorespiratory capacity, mortality, and
      complications in the postoperative phase. However, the physiological response
      elicited by these tests in obese people is unknown. This study analyzed and
      compared cardiopulmonary fitness (oxygen uptake [VO2] and CO2 output [VCO2]) in
      the ISWT and 6MWT in obese adults using a telemetry system. METHODS: Fifteen
      obese patients (10 women; mean age 39.4 +/- 10.1 years; mean body mass index 43.5
      +/- 6.8 kg/m(2)) with normal forced vital capacity (% FVC 93.7) performed the
      6MWT and ISWT in the field in this cross-sectional study. Metabolic (VO 2pk,
      VCO2) and respiratory (minute ventilation; VE) variables were recorded using
      telemetry. RESULTS: Obese patients performed the ISWT with an incremental and
      exponential cardiopulmonary response, with higher VO 2pk (15.4 +/- 2.9
      ml/kg/min), VCO2 (1.7 +/- 0.7 l/min), and VE (51.4 +/- 21.3 l/min) than the 6MWT
      (VO 2pk = 13.2 +/- 2.59 ml/kg/min, VCO2 = 1.4 +/- 0.6 l/min; VE = 41.2 +/- 16.6
      l/min (all p < 0.01). They also demonstrated more effort intensity, assessed by
      VO2, (p = 0.006) and heart rate (p = 0.04) in the ISWT than the 6MWT. In the
      6MWT, patients showed a fast rise in ventilatory and metabolic response, reaching
      a plateau. CONCLUSION: The ISWT test generated superior metabolic and ventilatory
      stress than the 6MWT and may be more suitable for assessing cardiopulmonary
      fitness than self-paced tests.

PMID- 25573459
TI  - Protective effects of apigenin against 1-methyl-4-phenylpyridinium ion-induced
      neurotoxicity in PC12 cells.
AB  - Parkinson's disease is recognized as the second most common neurodegenerative
      disorder after Alzheimer's disease, characterized by the loss of dopominergic
      neurons in the substantia nigra pars compacta and can be experimentally mimicked
      by the use of the neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP(+)), in in
      vitro models. In this study, we investigated the potential protective effects of
      apigenin (AP), galangin and genkwanin, naturally occurring plant flavonoids, on
      the MPP(+)-induced cytotoxicity in cultured rat adrenal pheochromocytoma cells
      (PC12 cells). The PC12 cells were pre-treated with various concentrations of the
      test compounds for 4 h, followed by the challenge with 1,000 uM MPP(+) for 48 h.
      We found that only pre-treatment with AP (3, 6 and 12 uM) before injury
      significantly increased cell viability, decreased the release of lactate
      dehydrogenase, reduced the level of intracellular reactive oxygen species and
      elevated mitochondrial membrane potential in the MPP(+)-treated PC12 cells. In
      addition, AP markedly suppressed the increased rate of apoptosis and the reduced
      Bcl-2/Bax ratio induced by MPP(+) in the PC12 cells. Taken together, the findings
      of this study demonstrate that AP exerts neuroprotective effects against MPP(+)
      induced neurotoxicity in PC12 cells, at least in part, through the inhibition of
      oxidative damage and the suppression of apoptosis through the mitochondrial
      pathway.

PMID- 25573460
TI  - Interrelations between herbage yield, alpha-tocopherol, beta-carotene, lutein,
      protein, and fiber in non-leguminous forbs, forage legumes, and a grass-clover
      mixture as affected by harvest date.
AB  - Pastures with diverse botanical composition may enhance animal-derived product
      quality. A recent study demonstrated high vitamin concentrations and yields in
      some forb species. The objectives of the present study were to investigate
      interrelations between herbage yields, vitamin concentrations, protein and fiber
      contents and analyze the effect of harvest date. We hypothesized that
      interrelations would be similar across investigated forage species. Four
      nonleguminous forbs: salad burnet (Sanguisorba minor), caraway (Carum carvi),
      chicory (Cichorium intybus), and ribwort plantain (Plantago lanceolata), three
      legumes: yellow sweet clover (Melilotus officinalis), lucerne (Medicago sativa),
      and birdsfoot trefoil (Lotus corniculatus) and a perennial ryegrass (Lolium
      perenne)-white clover (Trifolium repens) mixture were sown in a field trial with
      two replicated and randomized blocks. Forage in 1.5 m * 9 m plots was grown in
      two consecutive years and cut four times per year (May-October). Analyses of
      variance were performed. In most herbages, alpha-tocopherol and beta-carotene
      were positively correlated as were beta-carotene and lutein; all vitamins were
      negatively correlated with fiber content and herbage yield. beta-Carotene was
      positively correlated with protein content. alpha-Tocopherol and beta-carotene
      contents were generally highest in October and lowest in July. Our results showed
      similar interrelationships in most investigated species, and we suggest that
      these species may be mixed when designing novel biodiverse mixtures for
      particular product quality characteristics. 

PMID- 25573461
TI  - Effect of glucocorticoids on growth and bone mineral density in children with
      nephrotic syndrome.
AB  - Glucocorticosteroids (GCs) are the first-line treatment for idiopathic nephrotic
      syndrome (NS), but prolonged administration interferes with growth and bone
      mineralization. We conducted a retrospective study to analyze the long-term
      impact of prednisone on growth and bone mineral density (BMD) in children with
      NS. Data from children with NS followed during almost 10 years were analyzed.
      Height and spine BMD values were converted to Z-scores (standard deviation [SD]).
      The mean cumulative dose of GCs received was calculated and correlated to
      patient's growth and spine BMD using linear regression and subgroup analysis. We
      included 30 patients diagnosed at 3.7 years old (interquartile range (IQR) 2.6
      4.8) and followed over 9.8 years (IQR 6.6-11.7). The one half of NS patients was
      steroid sensitive and one half dependent or resistant. The median cumulative dose
      of GCs received was 0.27 mg/kg/day (IQR 0.18-0.35). Growth and spine BMD were
      both negatively associated with the cumulative dose of GCs (P=0.001 and P=0.037,
      respectively). Final height Z-scores were significantly lower in patients
      receiving >0.2 mg/kg/day GCs (P=0.001). No difference was observed in spine BMD
      between subgroups. CONCLUSION: Increasing doses of GCs were significantly
      associated with lower height and BMD Z-scores. A significant effect on growth was
      observed with cutoff doses above 0.2 mg/kg/day.

PMID- 25573463
TI  - The forgotten species.

PMID- 25573464
TI  - Changing practice: red blood cell typing by molecular methods for patients with
      sickle cell disease.
AB  - BACKGROUND: Extended red blood cell (RBC) antigen matching is recommended to
      limit alloimmunization in patients with sickle cell disease (SCD). DNA-based
      testing to predict blood group phenotypes has enhanced availability of antigen
      negative donor units and improved typing of transfused patients, but replacement
      of routine serologic typing for non-ABO antigens with molecular typing for
      patients has not been reported. STUDY DESIGNS AND METHODS: This study compared
      the historical RBC antigen phenotypes obtained by hemagglutination methods with
      genotype predictions in 494 patients with SCD. For discrepant results, repeat
      serologic testing was performed and/or investigated by gene sequencing for silent
      or variant alleles. RESULTS: Seventy-one typing discrepancies were identified
      among 6360 antigen comparisons (1.1%). New specimens for repeat serologic testing
      were obtained for 66 discrepancies and retyping agreed with the genotype in 64
      cases. One repeat Jk(b-) serologic phenotype, predicted Jk(b+) by genotype, was
      found by direct sequencing of JK to be a silenced allele, and one N typing
      discrepancy remains under investigation. Fifteen false-negative serologic results
      were associated with alleles encoding weak antigens or single-dose Fy(b)
      expression. CONCLUSIONS: DNA-based RBC typing provided improved accuracy and
      expanded information on RBC antigens compared to hemagglutination methods,
      leading to its implementation as the primary method for extended RBC typing for
      patients with SCD at our institution.

PMID- 25573462
TI  - Characteristics and outcomes of human parechovirus infection in infants (2008
      2012).
AB  - Human parechoviruses (HPeVs) cause a spectrum of disease ranging from self
      limiting illness to severe disease and, sometimes, death. We describe the
      clinical characteristics and outcomes of HPeV infection in infants. The study
      describes the clinical and laboratory characteristics and outcomes of infants
      with HPeV infection during 2008-2012, from three paediatric hospitals in London
      each with a paediatric intensive care unit. The infants were retrospectively
      identified through laboratory and patient discharge databases and diagnosed
      through HPeV PCR. Fifty infants were identified. Half required admission to PICU.
      Infants less than 3 months were more likely to require PICU (16/25: p < 0.01).
      Clinical signs at presentation were often indistinguishable from those of
      bacterial sepsis and meningitis, but inflammatory markers were nearly always (95
      % of cases) within normal ranges. Brain MRI showed white matter changes in 10/12
      infants. Three of 19 infants with follow-up data (16 %) had significant
      neurological sequelae. CONCLUSION: HPeV may cause severe disease and long-term
      neurological sequelae in young infants. HPeV should be considered in infants with
      clinical features of sepsis/meningitis with normal CSF microscopy. Prospective
      observational studies are warranted to better define the epidemiology of
      infection and thus inform future treatment trials.

PMID- 25573466
TI  - Nanoliposomes containing Eucalyptus citriodora as antibiotic with specific
      antimicrobial activity.
AB  - Bacterial infections are a serious issue for public health and represent one of
      the major challenges of modern medicine. In this work, a selective antimicrobial
      strategy based on triggering of pore-forming toxin, which is secreted by
      infective bacteria, was designed to fight Staphylococcus aureus. The
      antimicrobial activity is realized by employing Eucalyptus citriodora oil as
      antibiotic which in this study is encapsulated in nanoliposomes. 

PMID- 25573465
TI  - Factor structure of the Behavior Rating Inventory of Executive Functions (BRIEF
      P) at age three years.
AB  - The preschool period is an important developmental period for the emergence of
      cognitive self-regulatory skills or executive functions (EF). To date, evidence
      regarding the structure of EF in preschool children has supported both unitary
      and multicomponent models. The aim of the present study was to test the factor
      structure of early EF as measured by the Behavior Rating Inventory of Executive
      Function-Preschool version (BRIEF-P). BRIEF-P consists of five subscales and
      three broader indexes, hypothesized to tap into different subcomponents of EF.
      Parent ratings of EF from a nonreferred sample of children recruited from the
      Norwegian Mother and Child Cohort Study (N = 1134; age range 37-47 months) were
      subjected to confirmatory factor analyses (CFA). Three theoretically derived
      models were assessed; the second-order three-factor model originally proposed by
      the BRIEF-P authors, a "true" first-order one-factor model and a second-order one
      factor model. CFA fit statistics supported the original three-factor solution.
      However, the difference in fit was marginal between this model and the second
      order one-factor model. A follow-up exploratory factor analysis (EFA) supported
      the existence of several factors underlying EF in early preschool years, with a
      considerable overlap with the five BRIEF-P subscales. Our results suggest that
      some differentiation in EF has taken place at age 3 years, which is reflected in
      behavior ratings. The internal consistency of the BRIEF-P five clinical subscales
      is supported. Subscale interrelations may, however, differ at this age from those
      observed in the preschool group as a whole.

PMID- 25573467
TI  - Promoters inducible by aromatic amino acids and gamma-aminobutyrate (GABA) for
      metabolic engineering applications in Saccharomyces cerevisiae.
AB  - A wide range of promoters with different strengths and regulatory mechanisms are
      valuable tools in metabolic engineering and synthetic biology. While there are
      many constitutive promoters available, the number of inducible promoters is still
      limited for pathway engineering in Saccharomyces cerevisiae. Here, we constructed
      aromatic amino-acid-inducible promoters based on the binding sites of Aro80
      transcription factor, which is involved in the catabolism of aromatic amino acids
      through transcriptional activation of ARO9 and ARO10 genes in response to
      aromatic amino acids. A dynamic range of tryptophan-inducible promoter strengths
      can be obtained by modulating the number of Aro80 binding sites, plasmid copy
      numbers, and tryptophan concentrations. Using low and high copy number plasmid
      vectors and different tryptophan concentrations, a 29-fold range of fluorescence
      intensities of enhanced green fluorescent protein (EGFP) reporter could be
      achieved from a synthetic U4C ARO9 promoter, which is composed of four repeats of
      Aro80 binding half site (CCG) and ARO9 core promoter element. The U4C ARO9
      promoter was applied to express alsS and alsD genes from Bacillus subtilis for
      acetoin production in S. cerevisiae, resulting in a gradual increase in acetoin
      titers depending on tryptophan concentrations. Furthermore, we demonstrated that
      gamma-aminobutyrate (GABA)-inducible UGA4 promoter, regulated by Uga3, can also
      be used in metabolic engineering as a dose-dependent inducible promoter. The wide
      range of controllable expression levels provided by these tryptophan- and GABA
      inducible promoters might contribute to fine-tuning gene expression levels and
      timing for the optimization of pathways in metabolic engineering. 

PMID- 25573468
TI  - Surfactin from Bacillus subtilis displays an unexpected anti-Legionella activity.
AB  - A contaminant bacterial strain was found to exhibit an antagonistic activity
      against Legionella pneumophila, the causative agent of Legionnaires' disease. The
      bacterial strain was identified as a Bacillus subtilis and named B. subtilis AM1.
      PCR analysis revealed the presence of the sfp gene, involved in the biosynthesis
      of surfactin, a lipopeptide with versatile bioactive properties. The bioactive
      substances were extracted from AM1 cell-free supernatant with ethyl acetate and
      purified using reversed phase HPLC (RP-HPLC). Subsequent ESI-MS analyses
      indicated the presence of two active substances with protonated molecular ions at
      m/z 1008 and 1036 Da, corresponding to surfactin isoforms. Structures of
      lipopeptides were further determined by tandem mass spectrometry and compared to
      the spectra of a commercially available surfactin mixture. Surfactin displays an
      antibacterial spectrum almost restricted to the Legionella genus (MICs range 1-4
      MUg/mL) and also exhibits a weak activity toward the amoeba Acanthamoeba
      castellanii, known to be the natural reservoir of L. pneumophila. Anti-biofilm
      assays demonstrated that 66 MUg/mL of surfactin successfully eliminated 90 % of a
      6-day-old biofilm. In conclusion, this study reveals for the first time the
      potent activity of surfactin against Legionella sp. and preformed biofilms thus
      providing new directions toward the use and the development of lipopeptides for
      the control of Legionella spread in the environment.

PMID- 25573469
TI  - Isolation of oxygenase genes for indigo-forming activity from an artificially
      polluted soil metagenome by functional screening using Pseudomonas putida strains
      as hosts.
AB  - Metagenomes contain the DNA from many microorganisms, both culturable and non
      culturable, and are a potential resource of novel genes. In this study, a 5.2-Gb
      metagenomic DNA library was constructed from a soil sample (artificially polluted
      with four aromatic compounds, i.e., biphenyl, phenanthrene, carbazole, and 3
      chlorobenzoate) in Escherichia coli by using a broad-host-range cosmid vector.
      The resultant library was introduced into naphthalene-degrading Pseudomonas
      putida-derived strains having deficiencies in their naphthalene dioxygenase
      components, and indigo-forming clones on the indole-containing agar plates were
      screened. Cosmids isolated from 29 positive clones were classified by their
      various properties (original screening hosts, hosts showing indigo-forming
      activity, and digestion patterns with restriction enzymes), and six
      representative cosmids were chosen. Sequencing and in vitro transposon
      mutagenesis of the six cosmids resulted in the identification of genes encoding
      putative class B and D flavoprotein monooxygenases, a multicomponent hydroxylase,
      and a reductase that were responsible for the indigo-forming activity in the host
      cells. Among them, the genes encoding the multicomponent hydroxylase were
      demonstrated to be involved in phenol degradation. Furthermore, two genes
      encoding ring-cleavage dioxygenases were also found adjacent to the genes
      responsible for the indigo formation, and their functions were experimentally
      confirmed. 

PMID- 25573470
TI  - The role of N1 domain on the activity, stability, substrate specificity and raw
      starch binding of amylopullulanase of the extreme thermophile Geobacillus
      thermoleovorans.
AB  - In order to understand the role of N1 domain (1-257 aa) in the amylopullulanase
      (gt-apu) of the extremely thermophilic bacterium Geobacillus thermoleovorans
      NP33, N1 deletion construct (gt-apuDeltaN) has been generated and expressed in
      Escherichia coli. The truncated amylopullulanase (gt-apuDeltaN) exhibits similar
      pH and temperature optima like gt-apu, but enhanced thermostability. The gt
      apuDeltaN has greater hydrolytic action and specific activity on pullulan than gt
      apu. The k cat (starch and pullulan) and K m (starch) values of gt-apuDeltaN
      increased, while K m (pullulan) decreased. The enzyme upon N1 deletion hydrolyzed
      maltotetraose as the smallest substrate in contrast to maltopentaose of gt-apu.
      The role of N1 domain of gt-apu in raw starch binding has been confirmed, for the
      first time, based on deletion and Langmuir-Hinshelwood kinetics. Furthermore, N1
      domain appears to exert a negative influence on the thermostability of gt-apu
      because N1 truncation significantly improves thermostability. 

PMID- 25573471
TI  - Sulfur volatiles of microbial origin are key contributors to human-sensed truffle
      aroma.
AB  - Truffles are symbiotic fungi in high demand for the aroma of their fruiting
      bodies which are colonized by a diverse microbial flora. Specific sulfur
      containing volatiles (thiophene derivatives) characteristic of the white truffle
      Tuber borchii were recently shown to be derived from the bacterial community
      inhabiting truffle fruiting bodies. Our aim here was to investigate whether
      thiophene derivatives contributed to the human-sensed aroma of T. borchii.
      Furthermore, we questioned whether the concentration of thiophene volatiles was
      affected by freezing or whether it differed in truffles from distinct
      geographical origins. Gas chromatography-olfactometry (GC-O) analysis revealed
      that thiophene derivatives were major contributors to the aroma of T. borchii. Of
      four thiophene derivatives detected in this study, 3-methyl-4,5-dihydrothiophene
      was the most important one in terms of its contribution to the overall aroma. The
      relative concentration of thiophene derivatives was unaffected by freezing;
      however, it differed in samples collected in distinct geographical locations
      (Italy versus New Zealand). The causes of this variability might be differences
      in storage conditions and/or in bacterial community composition of the fruiting
      bodies; however, further work is needed to confirm these hypotheses. Overall, our
      results demonstrate that thiophene derivatives are major contributors to the
      human-sensed aroma of T. borchii.

PMID- 25573472
TI  - Two UDP-glucuronic acid decarboxylases involved in the biosynthesis of a
      bacterial exopolysaccharide in Paenibacillus elgii.
AB  - Xylose is described as a component of bacterial exopolysaccharides in only a
      limited number of bacterial strains. A bacterial strain, Paenibacillus elgii, B69
      was shown to be efficient in producing a xylose-containing exopolysaccharide.
      Sequence analysis was performed to identify the genes encoding the uridine
      diphosphate (UDP)-glucuronic acid decarboxylase required for the synthesis of UDP
      xylose, the precursor of the exopolysaccharide. Two sequences, designated as
      Peuxs1 and Peuxs2, were found as the candidate genes for such enzymes. The
      activities of the UDP-glucuronic acid decarboxylases were proven by heterologous
      expression and real-time nuclear magnetic resonance analysis. The intracellular
      activity and effect of these genes on the synthesis of exopolysaccharide were
      further investigated by developing a thymidylate synthase based knockout system.
      This system was used to substitute the conventional antibiotic resistance gene
      system in P. elgii, a natural multi-antibiotic resistant strain. Results of
      intracellular nucleotide sugar analysis showed that the intracellular UDP-xylose
      and UDP-glucuronic acid levels were affected in Peuxs1 or Peuxs2 knockout
      strains. The knockout of either Peuxs1 or Peuxs2 reduced the polysaccharide
      production and changed the monosaccharide ratio. No polysaccharide was found in
      the Peuxs1/Peuxs2 double knockout strain. Our results show that P. elgii can be
      efficient in forming UDP-xylose, which is then used for the synthesis of xylose
      containing exopolysaccharide.

PMID- 25573473
TI  - Rapid formation of nitrifying granules treating high-strength ammonium wastewater
      in a sequencing batch reactor.
AB  - Short initial settling time and rapidly increased ammonium nitrogen loading were
      employed to cultivate nitrifying granular sludge treating inorganic wastewater
      with 1000 mg/L ammonium nitrogen. It was found that the nitrifying granule
      dominant sludge was formed in a sequencing batch reactor (SBR) with influent
      ammonium concentration increased from 200 to 1000 mg N/L within 55 days. During
      the following 155-day operation period, nitrifying granules exhibited good
      performance with an ammonium removal efficiency of 99%. In the meantime, sludge
      volume index (SVI) decreased from 92 to 15 mL/g and the mean size of the
      nitrifying granules increased from 106 to 369 MUm. Mixed liquor suspended solids
      (MLSS) decreased from the initial 6.4 to around 3 g/L during the granulation
      period and increased to over 10 g/L at the end of the operation. The long-term
      stability of nitrifying granules and the reactor performance were not negatively
      affected by inhibition from free ammonia (FA) and free nitrous acid (FNA) in this
      study. This makes the granule sludge technology promising in treating high
      strength ammonium wastewater in practice.

PMID- 25573474
TI  - Enhancing stress tolerance by overexpression of a methionine sulfoxide reductase
      A (MsrA) gene in Pleurotus ostreatus.
AB  - Proteins are subjected to modification by reactive oxygen species (ROS), and
      oxidation of specific amino acid residues can impair their biological functions.
      Methionine as a sulfur-containing amino acid is easily oxidized to methionine
      sulfoxide (MetSO). The modified methionine can be repaired by methionine
      sulfoxide reductase (Msr), an enzyme that reverses oxidation of methionine in
      proteins. In this study, a methionine sulfoxide reductase A (PoMsrA) gene from
      Pleurotus ostreatus was cloned and characterized. Furthermore, the function of
      PoMsrA gene was analyzed by overexpression in P. ostreatus via Agrobacterium
      mediated transformation. Stable integration of the target gene into the genome of
      P. ostreatus was confirmed by PCR, fluorescence observation, and Southern blot
      hybridization. qRT-PCR analysis showed that PoMsrA was highly expressed in the
      stage of mature and young fruiting bodies as well as the osmotic stress condition
      of 0.3 M NaCl. Additionally, the transgenic strains with PoMsrA overexpression
      exhibited an enhanced tolerance to high temperature, high osmotic stress, and
      oxidative stress. This suggests that PoMsrA is an active player in the protection
      of the cellular proteins from oxidative stress damage.

PMID- 25573475
TI  - Erratum to: Insights into the substrate specificity and synergy with mannanase of
      family 27 alpha-galactosidases from Neosartorya fischeri P1.

PMID- 25573476
TI  - Persistence of Toxoplasma gondii in the central nervous system: a fine-tuned
      balance between the parasite, the brain and the immune system.
AB  - Upon infection of humans and animals with Toxoplasma gondii, the parasites
      persist as intraneuronal cysts that are controlled, but not eliminated by the
      immune system. In particular, intracerebral T cells are crucial in the control of
      T. gondii infection and are supported by essential functions from other leukocyte
      populations. Additionally, brain-resident cells including astrocytes, microglia
      and neurons contribute to the intracerebral immune response by the production of
      cytokines, chemokines and expression of immunoregulatory cell surface molecules,
      such as major histocompatibility (MHC) antigens. However, the in vivo behaviour
      of these individual cell populations, specifically their interaction during
      cerebral toxoplasmosis, remains to be elucidated. We discuss here what is known
      about the function of T cells, recruited myeloid cells and brain-resident cells,
      with particular emphasis on the potential cross-regulation of these cell
      populations, in governing cerebral toxoplasmosis.

PMID- 25573477
TI  - Analysis of SOD1 polymorphisms in Polish population with pseudoexfoliation
      syndrome.

PMID- 25573481
TI  - Teaching the interpretation of electrocardiograms: which method is best?
AB  - BACKGROUND: Electrocardiogram (ECG) interpretation is poorly performed at
      undergraduate and post-graduate level. Incorrect ECG interpretation can lead to
      serious clinical error. Despite the incorporation of computerized ECG
      interpretation software into modern ECG machines, the sensitivity and specificity
      of current technology remain poor, emphasizing the on-going need for doctors to
      perform ECG interpretation accurately. PURPOSE: This is the first review in this
      important area and aims to critically evaluate the current literature in relation
      to the optimal format and method of teaching ECG interpretation at undergraduate
      and postgraduate level. CONCLUSIONS: No single method or format of teaching is
      most effective in delivering ECG interpretation skills; however, self-directed
      learning appears to be associated with poorer interpretation competence.
      Summative in preference to formative assessment is associated with improved
      interpretation competence. Web-based learning offers a promising modern approach
      to learning ECG interpretation, though caution must be exercised in accessing
      user-uploaded content to supplement learning.

PMID- 25573478
TI  - Retinal pericytes and cytomegalovirus infectivity: implications for HCMV-induced
      retinopathy and congenital ocular disease.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) is the leading infectious cause of
      vision loss among congenitally infected children. Retinal pericytes play an
      essential role in maintaining retinal vascular and endothelial cell
      proliferation. However, the role of retinal pericytes in ocular HCMV pathogenesis
      is unknown. METHODS: Retinal pericytes were exposed to clinical (SBCMV) and lab
      strains of HCMV; infectivity was analyzed by microscopy, immunofluorescence and
      qRT-PCR (reverse transcription polymerase chain reaction). Cytokine expression
      was examined by Luminex assay. Recombinant HCMV-GPF was used to examine viral
      replication kinetics. A Tricell culture model of the inner blood-retinal barrier
      (IBRB) was examined for cell type infectivity using immunohistochemistry.
      RESULTS: Retinal pericytes expressed the biomarker neuron-glial antigen 2.
      Antigenic expression profiles for several cytoskeletal, cell adhesion and
      inflammatory proteins were shared by both retinal and brain pericytes. Infected
      pericytes showed cytomegalic cytopathology and expressed mRNAs for the major
      immediate protein (MIE) and HCMV phosphorylated envelop protein 65. qRT-PCR
      analysis showed full lytic replication of HCMV in retinal pericytes. Pericytes
      exposed to SBCMV for 9 days expressed higher levels of vascular endothelial cell
      growth factor mRNA compared to controls. Luminex analysis of supernatants from
      SBCMV-infected retinal pericytes had increased levels of macrophage inflammatory
      protein-1alpha, beta-2 microglobulin (B2-m), matrix metalloproteinase-3 and -9
      (MMP3/9), and lower levels of IL-6 and IL-8 compared to controls. At 24 hours
      post infection, pericytes expressed higher levels of IL-8, TIMP-1 (tissue
      inhibitor of metalloproteinase-1), and RANTES (regulated upon activation normal T
      cell-expressed and presumably secreted) but lower levels of MMP9. Time course
      analysis showed that both brain and retinal pericytes were more permissive for
      HCMV infection than other cellular components of the BBB (blood-brain barrier)
      and IBRB. Using a Tricell culture model of the IBRB (retinal endothelial,
      pericytes, Muller cells), retinal pericytes were most permissive for SBCMV
      infection. SBCMV infection of this IBRB Tricell mixture for 96 hours resulted in
      increased levels of IL-6, MMP9, and stem cell factor with a concomitant decrease
      in granulocyte-macrophage colony-stimulating factor and TNF-alpha. CONCLUSION: In
      retinal pericytes, HCMV induces proinflammatory and angiogenic cytokines. In the
      IBRB, pericytes likely serve as an amplification reservoir which contributes to
      retinal inflammation and angiogenesis.

PMID- 25573483
TI  - A note on modelling incomplete contingency tables with censored cells.

PMID- 25573484
TI  - Therapeutic advances in the treatment of polycystic kidney disease.
AB  - The spectrum of polycystic kidney disease (PKD) comprises a family of inherited
      syndromes defined by renal cyst formation and growth, progressive renal function
      loss and variable extrarenal manifestations. The most common form, autosomal
      dominant PKD is caused by mutations in one of two genes, PKD1 or PKD2. Recent
      developments in genomic and proteomic medicine have resulted in the discovery of
      novel genes implicated in the wide variety of less frequent, recessive PKD
      syndromes. Cysts are the disease, and overall cystic burden, measured by MRI as
      total kidney volume, is being established as the best available biomarker of
      disease progression. Current state-of-the-art therapy is aimed at quality
      treatment for chronic renal insufficiency and cyst-related complications. Recent
      therapeutic studies have focused on mechanisms reducing intracellular cyclic AMP
      levels, blocking the renin-angiotensin-aldosterone system and inhibiting the mTOR
      signaling pathway. PKD therapies with vasopressin antagonists and somatostatin
      analogues result in the reduction of intracellular cAMP levels and have shown
      limited clinical success, but side effects are prominent. Similarly, mTOR pathway
      inhibition has not shown significant therapeutic benefits. While the HALT-PKD
      study will answer questions by the end of 2014 about the utility of renin
      angiotensin-aldosterone system blockade and aggressive blood pressure control,
      the next generation of PKD therapy studies targeting proliferative mechanisms of
      cyst expansion are already under way. Advances in research on the molecular
      mechanisms of cystogenesis will help design novel targeted PKD therapies in the
      future.

PMID- 25573482
TI  - The effects of phytochrome-mediated light signals on the developmental
      acquisition of photoperiod sensitivity in rice.
AB  - Plants commonly rely on photoperiodism to control flowering time. Rice
      development before floral initiation is divided into two successive phases: the
      basic vegetative growth phase (BVP, photoperiod-insensitive phase) and the
      photoperiod-sensitive phase (PSP). The mechanism responsible for the transition
      of rice plants into their photoperiod-sensitive state remains elusive. Here, we
      show that se13, a mutation detected in the extremely early flowering mutant X61
      is a nonsense mutant gene of OsHY2, which encodes phytochromobilin (PPhiB)
      synthase, as evidenced by spectrometric and photomorphogenic analyses. We
      demonstrated that some flowering time and circadian clock genes harbor different
      expression profiles in BVP as opposed to PSP, and that this phenomenon is chiefly
      caused by different phytochrome-mediated light signal requirements: in BVP,
      phytochrome-mediated light signals directly suppress Ehd2, while in PSP,
      phytochrome-mediated light signals activate Hd1 and Ghd7 expression through the
      circadian clock genes' expression. These findings indicate that light receptivity
      through the phytochromes is different between two distinct developmental phases
      corresponding to the BVP and PSP in the rice flowering process. Our results
      suggest that these differences might be involved in the acquisition of
      photoperiod sensitivity in rice. 

PMID- 25573485
TI  - CTT1 overexpression increases life span of calorie-restricted Saccharomyces
      cerevisiae deficient in Sod1.
AB  - Studies using different organisms revealed that reducing calorie intake, without
      malnutrition, known as calorie restriction (CR), increases life span, but its
      mechanism is still unkown. Using the yeast Saccharomyces cerevisiae as eukaryotic
      model, we observed that Cu, Zn-superoxide dismutase (Sod1p) is required to
      increase longevity, as well as to confer protection against lipid and protein
      oxidation under CR. Old cells of sod1 strain also presented a premature induction
      of apoptosis. However, when CTT1 (which codes for cytosolic catalase) was
      overexpressed, sod1 and WT strains showed similar survival rates. Furthermore,
      CTT1 overexpression decreased lipid peroxidation and delayed the induction of
      apoptotic process. Superoxide is rapidly converted to hydrogen peroxide by
      superoxide dismutase, but it also undergoes spontaneous dismutation albeit at a
      slower rate. However, the quantity of peroxide produced from superoxide in this
      way is two-fold higher. Peroxide degradation, catalyzed by catalase, is of vital
      importance, because in the presence of a reducer transition metal peroxide is
      reduced to the highly reactive hydroxyl radical, which reacts indiscriminately
      with most cellular constituents. These findings might explain why overexpression
      of catalase was able to overcome the deficiency of Sod1p, increasing life span in
      response to CR.

PMID- 25573486
TI  - Impact of M36I polymorphism on the interaction of HIV-1 protease with its
      substrates: insights from molecular dynamics.
AB  - BACKGROUND: Over the last decades, a vast structural knowledge has been gathered
      on the HIV-1 protease (PR). Noticeably, most of the studies focused the B
      subtype, which has the highest prevalence in developed countries. Accordingly,
      currently available anti-HIV drugs target this subtype, with considerable
      benefits for the corresponding patients. RESULTS: Herein, we used molecular
      dynamics simulations to investigate the role of this polymorphism on the
      interaction of PR with six of its natural cleavage-sites substrates. CONCLUSIONS:
      With multiple approaches and analyses we identified structural and dynamical
      determinants associated with the changes found in the binding affinity of the
      M36I variant. This mutation influences the flexibility of both PR and its
      complexed substrate. The observed impact of M36I, suggest that combination with
      other non-B subtype polymorphisms, could lead to major effects on the interaction
      with the 12 known cleavage sites, which should impact the virion maturation.

PMID- 25573487
TI  - Sialylation by beta-galactoside alpha-2,6-sialyltransferase and N-glycans
      regulate cell adhesion and invasion in human anaplastic large cell lymphoma.
AB  - The interaction between cell surface glycans and extracellular matrix (ECM)
      including galectins is known to be closely associated with tumor cell adhesion,
      invasion and metastasis. We analyzed the roles of cell surface sialylation or
      glycosylation in galectin or ECM-mediated cell adhesion and invasion of human
      malignant lymphoma cells. Neuraminidase from Arthrobacter ureafaciens (AU)
      treatment resulted in reduction of cell adhesion to galectin-8 in human
      anaplastic large cell lymphoma (H-ALCL) which was established in our laboratory.
      The knockdown of beta-galactoside alpha-2,6-sialyltrans-ferase (ST6Gal1) by siRNA
      showed inhibition of ST6Gal1 expression in the cytoplasm of H-ALCL cells on
      immunohistochemical findings, and showed dramatic enhancement of cell adhesion to
      galectin-8. On the other hand, alpha-2,3-specific neuraminidase treatment
      resulted in moderate enhancement of cell adhesion to galectin-8. We performed
      chemically artificial modification of cell surface O-glycans by treatment of
      benzyl 2-acetamido-2-deoxy-alpha-D-galactopyranoside (Bz-alpha-GalNAc) in H-ALCL.
      Cell adhesion to galectin-8 was enhanced by treatment of Bz-alpha-GalNAc
      suggesting that inhibition of elongation of O-glycans may enhance cell adhesion
      to galectin-8 in H-ALCL cells. On the other hand inhibition of elongation of N
      glycosylation by tunicamycin (TM) resulted in inhibition of Phaseolus vulgaris-L
      (L-PHA) lectin-binding activity and inhibited cell adhesion to galectin-8,
      laminin and fibronectin. Neuraminidase treatment enhanced cell adhesion to
      laminin, and knockdown of ST6Gal1 resulted in enhancement of cell adhesion to
      laminin, but not to fibronectin, collagen type 1 and 4. Galectin-8 pre-treatment
      dramatically enhanced cell adhesion to laminin and neuraminidase treatment also
      enhanced cell adhesion to laminin in combination with galectin-8. Rho inhibitor,
      C3-transferase pre-treatment resulted in inhibition of cell invasion to galectin
      8. Phosphatidylinositol 3-phosphate kinase (PI3K) inhibitor, wortmannin inhibits
      the cell invasive capacity to galectin-8. Neuraminidase treatment induces growth
      inhibition of lymphoma cells by galectin-8.

PMID- 25573488
TI  - Dialysis dose and risk factors for death among ESRD patients treated with twice
      weekly hemodialysis: a prospective cohort study.
AB  - BACKGROUND/AIMS: We aimed to define the dosing and risk factors for death in
      patients undergoing twice-weekly hemodialysis. METHODS: A prospective multi
      center cohort study was conducted with one-year observation. Patients treated
      with twice- or thrice-weekly hemodialysis were identified. Death and first
      admission were the outcomes. spKt/V was a factor of interest. RESULTS: We
      enrolled 504 twice-weekly and 169 thrice-weekly hemodialysis patients. The mean
      weekly values of spKt/V in the two groups were 3.4 and 5.1. The one-year survival
      rate and times to hospitalization were similar in both groups. The hazard ratios
      for death in higher spKt/V quartile was not associated with lower mortality, p =
      0.70. The four significant predictors for death were serum albumin, HR = 2.6,
      current smoking, HR = 19.3, age, HR = 1.1, and the Index of Coexistent Disease
      [ICED], HR = 1.9. CONCLUSION: The effect of spKt/V on short-term mortality was
      not obvious in twice-weekly dialysis patients. Attention should be paid to
      patients who smoke, have hypoalbuminemia, are elderly, or have a high ICED.

PMID- 25573489
TI  - Pseudoaneurysm of the sinus of valsalva.

PMID- 25573490
TI  - TPMT alleles in the Moroccans.

PMID- 25573492
TI  - Pancreatitis in incretin-based therapies.

PMID- 25573493
TI  - Gastroparesis and ischemic gastric ulcers in a patient with rheumatoid arthritis
      receiving adalimumab therapy.

PMID- 25573491
TI  - Cobalt protoporphyrin protects the liver against apoptosis in rats of brain
      death.
AB  - Brain death (BD) leads to a marked increase in apoptosis, which influences the
      viability of donor organs. Induction of heme oxygenase 1 (HO-1) has been shown to
      exert beneficial effects in different liver injury models. Therefore, we examined
      the effect of pretreating rats with cobalt protoporphyrin (CoPP), an HO-1
      inducer, on apoptosis in liver during BD and elucidated the mechanisms involved.
      First, rats were killed at 0, 1, 2, 4 and 6 h after BD induction to examine the
      expression of hepatic HO-1. Second, rats were randomly divided into four groups
      (n=6): (S group) rats undergoing sham operation, (CS group) rats pretreated with
      CoPP for 24 h before the sham operation, (B group) rats undergoing BD for 6 h,
      (CB group) rats pretreated with CoPP for 24 h before BD induction. The expression
      levels of hepatic HO-1 mRNA and protein in rats increased at 0, 1, 2, 4 and 6h
      after BD induction, compared with sham operated rats. In the CB group compared
      with the B group, the increased hepatic expression of HO-1 correlated with a
      significant decrease in serum ALT/AST levels, fewer apoptotic cells in liver,
      increased hepatic expression of Mcl-1 and Bcl-2, and decreased hepatic expression
      of Bax, cytosolic cytochrome c and cleaved caspase-3. CoPP inhibits apoptosis in
      liver of BD rats in part via modulating the mitochondrial apoptosis pathway. HO-1
      may serve as a potential target for improving the quality of organs from BD
      donors.

PMID- 25573494
TI  - Cholestatic hepatitis due to Ecballium elaterium ingestion.
AB  - Ecballium elaterium is an herbaceous plant belonging to the Cucurbitaceae family.
      This plant is fairly common in the Mediterranean regions. It is frequently
      consumed in infusion, mixture of fruit or even in aerosol in cases of fever or
      flu. This plant is known for its respiratory and ocular toxicity. Hepatotoxicity
      has never been described in the literature. We report a case of acute cholestatic
      hepatitis due to Ecballium elaterium in a 39 years old patient, with no past
      medical history.

PMID- 25573495
TI  - Fundamental immunological problems associated with "transmissible spongiform
      encephalopathies".
AB  - "Bovine spongiform encephalopathy", "scrapie", as well as Creutzfeldt-Jakob
      disease and kuru belong to a group of related neurological conditions termed
      "transmissible spongiform encephalopathies". These diseases are based on the LD50
      measurement whereby saline brain homogenates are injected into experimental
      animals and when 50% of them develop symptoms, this is considered as transmission
      of the disease, but the gold standard for diagnosis is autopsy examination.
      However, an untenable assumption is being made in that saline brain homogenates
      do not cause tissue damage but it is known since the time of Pasteur, that they
      give rise to "post-rabies vaccination allergic encephalomyelitis". This is the
      fundamental flaw in the diagnosis of these diseases. A way forward, however, is
      to examine infectious agents, such as Acinetobacter which show molecular mimicry
      with myelin and elevated levels of antibodies to this microbe are found in
      multiple sclerosis patients and animals affected by "bovine spongiform
      encephalopathy". 

PMID- 25573496
TI  - Role of complement component C4 in treatment response and disease progression in
      chronic hepatitis C patients.
AB  - The basis of hepatitis C virus (HCV) evasion of immune system and its response to
      treatment is still elusive. There have been studies where the level of C4 has
      been found to be associated with HCV persistence and disease progression. This
      study aims to find out relationship between levels of C4 in serum, and its
      functional SNPs with response to treatment. The study included 84 patients with
      CHC who received treatment and 75 healthy controls. C4 expression, both at mRNA
      and protein level, was estimated by Real time and ELISA respectively. Its
      functional SNP's genotyped by AS-PCR. The mean +/- SD baseline C4 levels between
      the disease and healthy cases was significantly different (1075.74 +/- 65.25 vs
      1593 +/- 24.55 ng/mL, P < 0.001). The mean +/- SD baseline C4 levels of CC, GC
      and GG genotype of rs2857009 in the healthy group were 1540.97 +/- 7.87, 1599.53
      +/- 11.75 and 1604.86 +/- 10.79 ng/mL, respectively (P < 0.001), whereas the
      levels in the CHC group were 1022.81 +/- 32.95, 1058.19 +/- 55.02 and 1150.26 +/-
      14.64 ng/mL, respectively (P < 0.001). CC genotype resulted in decreased C4 mRNA
      levels compared to GG genotype in healthy group (3.81-fold) and CHC group (1.4
      fold). The CC genotype of rs2857009 is associated with reduced expression of C4,
      both at mRNA and protein level. The C4 serum level at baseline and total protein
      were found to be independent predictors for treatment response. New predictive
      score using the above factors, a value of >= 0.542 was found to predict positive
      response to treatment. Increased age, rs2857009 SNP and HCV genotype were
      associated with disease progression.

PMID- 25573497
TI  - Ten tips on how to win the war against resistance to antibiotics.

PMID- 25573499
TI  - Ten major priorities for intensive care in India.

PMID- 25573498
TI  - Increasing participation in critical care studies: the need to understand
      surrogate decision-makers for critically ill patients.

PMID- 25573500
TI  - Improving ultrasonic measurement of diaphragmatic excursion after cardiac surgery
      using the anatomical M-mode: a randomized crossover study.
AB  - PURPOSE: Motion-mode (MM) echography allows precise measurement of diaphragmatic
      excursion when the ultrasound beam is parallel to the diaphragmatic displacement.
      However, proper alignment is difficult to obtain in patients after cardiac
      surgery; thus, measurements might be inaccurate. A new imaging modality named the
      anatomical motion-mode (AMM) allows free placement of the cursor through the
      numerical image reconstruction and perfect alignment with the diaphragmatic
      motion. Our goal was to compare MM and AMM measurements of diaphragmatic
      excursion in cardiac surgical patients. METHODS: Cardiac surgical patients were
      studied after extubation. The excursions of the right and left hemidiaphragms
      were measured by two operators, an expert and a trainee, using MM and AMM
      successively, according to a blinded, randomized, crossover sequence. Values were
      averaged over three consecutive respiratory cycles. The angle between the MM and
      AMM cursors was quantified for each measurement. RESULTS: Fifty patients were
      studied. The mean (+/-SD) angle between the MM and AMM cursors was 37 degrees  +/
      16 degrees . The diaphragmatic excursion as measured by experts was 1.8 +/- 0.7
      cm using MM and 1.5 +/- 0.5 cm using AMM (p < 0.001). Overall, the diaphragmatic
      excursion as estimated by MM was larger than the value obtained with AMM in 75 %
      of the measurements. Bland-Altman analysis showed tighter limits of agreement
      between experts and trainees with AMM [bias: 0.0 cm; 95 % confidence interval
      (CI): 0.8 cm] than with MM (bias: 0.0 cm; 95 % CI: 1.4 cm). CONCLUSION: MM
      overestimates diaphragmatic excursion in comparison to AMM in cardiac surgical
      patients. Using MM may lead to a lack of recognition of diaphragmatic
      dysfunction.

PMID- 25573501
TI  - Ten tips for managing critically ill burn patients: follow the RASTAFARI!

PMID- 25573502
TI  - A novel vertebrates Toll-like receptor counterpart regulating the anti-microbial
      peptides expression in the freshwater crayfish, Procambarus clarkii.
AB  - Toll-like receptors (TLRs) play an important role in regulation of anti-microbial
      peptides (AMPs) expression. A novel vertebrates TLR counterpart named PcToll, was
      firstly identified from the freshwater crayfish, Procambarus clarkii.
      Phylogenetic analysis showed that PcToll together with Drosophila melanogaster
      and Anopheles gambiae Toll9 were clustered with human Tolls. PcToll was mainly
      expressed in hepatopancreas and gills and it also could be detected in hemocytes,
      heart, stomach and intestine. PcToll was upregulated in hemocytes and gills post
      24 h Vibrio anguillarum challenge. In hepatopancreas and intestine, the highest
      expression level of PcToll could be observed at 12 h V. anguillarum challenge. In
      hemocytes, PcToll went up post 24 h Staphylococcus aureus challenge and in gills,
      the expression level of PcToll showed no obvious change from 2 to 24 h S. aureus
      challenge. In hepatopancreas post 12 h S. aureus challenge, PcToll was
      upregulated and it showed obvious upregulation post 12 h S. aureus challenge in
      intestine. RNAi results showed that PcToll was involved in regulation of crustins
      (Cru1, Cru2), anti-lipopolysaccharide factor 2 (ALF2) and lysozyme 1 (Lys1)
      expression. Overexpression of PcToll in Drosophila S2 cells could induce
      Drosophila Attacin (Atta), Metchnikowin (Mtk), Drosomycin (Drs) and shrimp
      Penaeidin (PEN4) expression. From the results, it could be speculated that PcToll
      might play important roles in crayfish innate immune defense.

PMID- 25573504
TI  - Challenges in treatment of posttraumatic stress disorder in refugees: towards
      integration of evidence-based treatments with contextual and culture-sensitive
      perspectives.
AB  - BACKGROUND: Research shows that trauma-focused therapy and multimodal
      interventions are the two most often used strategies in treatment of refugees
      suffering from posttraumatic stress disorder (PTSD). While preliminary evidence
      suggests that trauma-focused approaches may have some efficacy, this could not be
      established for multimodal interventions. However, it may be that multimodal
      interventions have been studied in more treatment-resistant refugees with very
      high levels of psychopathology, disability, and chronicity. In the past decades,
      various models for understanding of the complex relationship between mental
      health problems and well-being have emerged. They aim at framing mental health
      problems in individualized, contextual, epigenetic, and culturally sensitive
      ways, and may be useful in tailoring content and timing of multimodal
      interventions. OBJECTIVE: To draw clinicians' attention to the possibility of
      using the Integrative Contextual Model for understanding and assessment of
      posttrauma mental health sequelae while tailoring multimodal interventions; to
      present a possible way of combining multimodal with evidence-based trauma-focused
      approaches; and to improve the understanding and treatment of PTSD and other
      mental health problems in refugee survivors of prolonged and repeated trauma.
      METHOD: Based on literature, clinical experience, and presentation of a fictional
      case, the use of the Integrative Contextual Model in tailoring the treatment of
      severe PTSD in a refugee patient is presented and discussed. RESULTS: The
      Integrative Contextual Model for understanding and assessing factors, which may
      play a role in causing and maintaining of PTSD and comorbidity in refugees, may
      help tailoring of multimodal interventions. These interventions can be combined
      with evidence-based trauma-focused treatments. CONCLUSION: The field of refugee
      mental health intervention and clinical practice with traumatized refugees may be
      enriched with the use of contextual and developmental models for assessment and
      conceptualization of posttrauma sequelae. Multimodal and trauma-focused
      interventions may be applied sequentially in a course of the treatment
      trajectory.

PMID- 25573503
TI  - Separate and overlapping specificities in rheumatoid arthritis antibodies binding
      to citrulline- and homocitrulline-containing peptides related to type I and II
      collagen telopeptides.
AB  - INTRODUCTION: Our objective was to find out if there are antibodies binding to
      homocitrulline-containing type I and II collagen carboxyterminal telopeptides in
      sera of patients with rheumatoid arthritis (RA), and if these antibodies cross
      react with citrulline and homocitrulline in the same peptide sequence. METHODS: A
      total of 72 RA and 72 control sera were analyzed for binding using enzyme-linked
      immunosorbent assay to citrulline- or homocitrulline-containing type I and II
      collagen carboxyterminal telopeptides, as well as to cyclic citrullinated peptide
      (CCP) and to mutated citrullinated vimentin (MCV). Specificities of the
      antibodies were tested using inhibition-ELISA. RESULTS: Of the RA sera, 39 (54%)
      and 41 (57%) were positive for binding to CCP and MCV, respectively. Further, 34
      (47%) and 30 (42%) of the patients had specific antibodies binding to and being
      inhibited by citrulline-containing type I collagen telopeptides and by citrulline
      containing type II collagen carboxyterminal telopeptides, respectively. The
      corresponding figures regarding homocitrulline-containing type I and
      homocitrulline-containing type II collagen telopeptides were 16 (22%) and 14
      (19%). Most of the patients, who were seropositive for citrullinated peptides,
      showed binding in multiple assays. A total of 10 (14%) RA patients were positive
      for all the tested peptide pairs, while 28 (39%) of them had antibodies that
      contained overlapping specifities between citrulline and homocitrulline in the
      same peptide sequence. CONCLUSIONS: Antibodies to both citrulline and
      homocitrulline containing type I and II collagen telopeptides can be found in
      sera of RA patients. These antibodies are not constant from one RA patient to
      another, but contain separate or overlapping specificities within the same
      peptide sequence varying between individuals. Our results suggest some
      relationship between citrulline and homocitrulline-recognizing antibodies, since
      homocitrulline antibodies exist mainly in individuals seropositive to anti-CCP
      and anti-MCV.

PMID- 25573505
TI  - M.I.A.M.I.: the whealth di$parity.

PMID- 25573506
TI  - Social disadvantage: perpetual origin of kidney disease.

PMID- 25573508
TI  - Early-life course socioeconomic factors and chronic kidney disease.
AB  - Kidney failure or ESRD affects approximately 650,000 Americans, whereas the
      number with earlier stages of CKD is much higher. Although CKD and ESRD are
      usually associated with adulthood, it is likely that the initial stages of CKD
      begin early in life. Many of these pathways are associated with low birth weight
      and disadvantaged socioeconomic status (SES) in childhood, translating childhood
      risk into later-life CKD and kidney failure. Social factors are thought to be
      fundamental causes of disease. Although the relationship between adult SES and
      CKD has been well established, the role of early childhood SES for CKD risk
      remains obscure. This review provides a rationale for examining the association
      between early-life SES and CKD. By collecting data on early-life SES and CKD, the
      interaction with other periods in the life course could also be studied, allowing
      for examination of whether SES trajectories (eg, poverty followed by affluence)
      or cumulative burden (eg, poverty at multiple time points) are more relevant to
      lifetime CKD risk. 

PMID- 25573507
TI  - Socioeconomic disparities in chronic kidney disease.
AB  - CKD is a national public health problem that afflicts persons of all segments of
      society. Although racial/ethnic disparities in advanced CKD including dialysis
      dependent populations have been well established, the finding of differences in
      CKD incidence, prevalence, and progression across different socioeconomic groups
      and racial and ethnic strata has only recently started to receive significant
      attention. Socioeconomics may exert both interdependent and independent effects
      on CKD and its complications and may confound racial and ethnic disparities.
      Socioeconomic constellations influence not only access to quality care for CKD
      risk factors and CKD treatment but may mediate many of the cultural and
      environmental determinants of health that are becoming more widely recognized as
      affecting complex medical disorders. In this article, we have reviewed the
      available literature pertaining to the role of socioeconomic status and economic
      factors in both non-dialysis-dependent CKD and ESRD. Advancing our understanding
      of the role of socioeconomic factors in patients with or at risk for CKD can lead
      to improved strategies for disease prevention and management. 

PMID- 25573509
TI  - Understanding the influence of educational attainment on kidney health and
      opportunities for improved care.
AB  - Educational attainment is an important but often overlooked contributor to health
      outcomes in patients with kidney disease. Those with lower levels of education
      have an increased risk of ESRD, complications of peritoneal dialysis, worse
      transplant outcomes, and mortality. Mediators of these associations are poorly
      understood but involve a complex interplay between health knowledge, behaviors,
      and socioeconomic and psychosocial factors. Interventions targeting these aspects
      of care have the potential to reduce disparities related to educational
      attainment; however, few programs have been described that specifically address
      this issue. Future research efforts should not only systematically assess level
      of educational attainment but also report the differential impact of
      interventions across educational strata. In addition, routine measurement of
      health literacy may be useful to identify high-risk patients independent of years
      of schooling. A better understanding of the influence of educational attainment
      on kidney health provides an opportunity to improve the care and outcomes of
      vulnerable patients with kidney disease. 

PMID- 25573510
TI  - Contextual poverty, nutrition, and chronic kidney disease.
AB  - Nutrition plays an important role in CKD outcomes. One of the strongest factors
      that affects nutrition is socioeconomic status as evidenced by the large body of
      epidemiologic data showing that income and education are directly associated with
      diet quality. Apart from individual-level markers of socioeconomic status such as
      income and education, contextual factors such as availability of and
      transportation to food outlets that provide healthy food options and the density
      of fast-food restaurants within particular regions markedly affect the ability of
      individuals to comply with nutrition recommendations. This is particularly true
      for nutrition guidelines most specific to individuals with CKD such as the
      consumption of protein, saturated fat, sodium, and phosphorus, all of which have
      been shown to affect CKD health and are influenced by the availability of healthy
      food options within individual neighborhood food environments. Because of the
      strong association of contextual poverty with the diet quality, any serious
      attempt to improve the diet of CKD patients must include a discussion of the
      environmental barriers that each individual faces in trying to access healthy
      foods, and health care providers should take account of these barriers when
      tailoring specific recommendations. 

PMID- 25573511
TI  - Environmental exposures, socioeconomics, disparities, and the kidneys.
AB  - Kidney disease disproportionately affects racial and ethnic minority populations,
      the poor, and the socially disadvantaged. The excess risk of kidney disease among
      minority and disadvantaged populations can only be partially explained by an
      excess of diabetes, hypertension, and poor access to preventive care. Disparities
      in the environmental exposure to nephrotoxicants have been documented in minority
      and disadvantaged populations and may explain some of the excess risk of kidney
      disease. High-level environmental and occupational exposure to lead, cadmium, and
      mercury are known to cause specific nephropathies. However, there is growing
      evidence that low-level exposures to heavy metals may contribute to the
      development of CKD and its progression. In this article, we summarize the excess
      risk of environmental exposures among minority and disadvantaged populations. We
      also review the epidemiologic and clinical data linking low-level environmental
      exposure to lead, cadmium, and mercury to CKD and its progression. Finally, we
      briefly describe Mesoamerican nephropathy, an epidemic of CKD affecting young men
      in Central America, which may have occupational and environmental exposures
      contributing to its development. 

PMID- 25573514
TI  - Dialysis for undocumented immigrants in the United States.
AB  - The United States offers near-universal coverage for treatment of ESRD.
      Undocumented immigrants with ESRD are the only subset of patients not covered
      under a national strategy. There are 2 divergent dialysis treatment strategies
      offered to undocumented immigrants in the United States, emergent dialysis and
      chronic outpatient dialysis. Emergent dialysis, offering dialysis only when
      urgent indications exist, is the treatment strategy in certain states. Differing
      interpretations of Emergency Medicaid statute by the courts and state and federal
      government have resulted in the geographic disparity in treatment strategies for
      undocumented immigrants with ESRD. The Patient Protection and Affordable Care Act
      of 2010 ignored the health care of undocumented immigrants and will not provide
      relief to undocumented patients with catastrophic illness like ESRD, cancer, or
      traumatic brain injuries. The difficult patient and provider decisions are
      explored in this review. The Renal Physicians Association Position Statement on
      uncompensated renal-related care for noncitizens is an excellent starting point
      for a framework to address this ethical dilemma. The practice of "emergent
      dialysis" will hopefully be found unacceptable in the future because of the fact
      that it is not cost effective, ethical, or humane. 

PMID- 25573513
TI  - Health policy, disparities, and the kidney.
AB  - Kidney care and public policy have been linked for 40 years, with various
      consequences to outcomes. The 1972 Social Security Amendment, Section 2991,
      expanded Medicare coverage for all modalities of dialysis and transplant services
      and non-kidney-related care to those with end-stage renal disease (ESRD)
      regardless of age. This first and only disease-specific entitlement program was a
      step toward decreasing disparities in access to care. Despite this, disparities
      in kidney disease outcomes continue as they are based on many factors. Over the
      last 4 decades, policies have been enacted to understand and improve the delivery
      of ESRD care. More recent policies include novel shared-risk payment models to
      ensure quality and decrease costs. This article discusses the impact or potential
      impact of selected policies on health disparities in advanced chronic kidney
      disease and ESRD. Although it is too early to know the consequences of newer
      policies (Affordable Care Act, ESRD Prospective Payment System, Quality Incentive
      Program, Accountable Care Organizations), their goal of improving access to
      timely patient-centered appropriate affordable and quality care should lessen the
      disparity gap. The Nephrology community must leverage this dynamic state of care
      delivery model redesign to decrease kidney-related health disparities. 

PMID- 25573512
TI  - Stress and the kidney.
AB  - The prevalence of CKD has increased considerably over the past 2 decades. The
      rising rates of CKD have been attributed to known comorbidities such as diabetes,
      hypertension, and obesity; however, recent research has begun to explore the
      degree to which social, economic, and psychological factors have implications for
      the prevalence and progression of CKD, especially among high-risk populations
      such as African Americans. It has been suggested that stress can have
      implications for CKD, but this area of research has been largely unexplored. One
      contributing factor associated with the paucity of research on CKD is that many
      of the social, psychological, and environmental stressors cannot be recreated or
      simulated in a laboratory setting. Social science has established that stress can
      have implications for health, and we believe that stress is an important
      determinant of the development and progression of CKD. We draw heavily from the
      social scientific and social epidemiologic literature to present an
      intersectional conceptual frame specifying how stress can have implications for
      kidney disease, its progression, and its complications through multiple stressors
      and pathways.

PMID- 25573515
TI  - Chronic kidney disease care in the US safety net.
AB  - The US Health Care System provides a patchwork of services, known as the safety
      net, for the uninsured, underinsured, and indigent populations who would
      otherwise have little access to health care services. Individuals who rely on
      safety-net facilities are from racial/ethnic minority groups, have low
      socioeconomic status, and often have low health literacy and/or limited English
      proficiency. They shoulder a disproportionate burden of CKD in the United States
      and experience excess CKD-associated morbidity and mortality. Suboptimal delivery
      of CKD care may be contributing and is an area of active translational research.
      Several initiatives that show promise in improving safety-net CKD care delivery
      include those that enhance diagnostic and management skills of primary care
      providers, rely on comprehensive care management programs led by nonphysicians,
      and leverage technology to enhance patient access to virtual nephrology
      expertise. Uncovering better ways to translate scientific evidence into practice
      for vulnerable patients with CKD is a formidable challenge that will require
      national surveillance of CKD quality measures across diverse ambulatory health
      systems, including safety nets. Only then will the nephrology community be to
      identify and share best practices to enhance health and mitigate disparities of
      care among patients with CKD.

PMID- 25573517
TI  - Contrasting anion recognition behaviour exhibited by halogen and hydrogen bonding
      rotaxane hosts.
AB  - A rotaxane host system containing a novel halogen bonding (XB) 5-iodo-1,2,3
      triazole functionalised pyridinium motif, within its axle component, has been
      prepared via a ring closing metathesis reaction, using chloride as a template.
      Proton NMR titration experiments, in competitive 1 : 1 CDCl3-CD3OD solvent media,
      showed the XB rotaxane selectively bound halides over larger, more basic
      oxoanions. An all hydrogen bonding proto-triazole containing rotaxane analogue
      was also prepared, which in stark contrast demonstrated a reversal in the anion
      selectivity trend, with a preference for dihydrogen phosphate over the halides
      which is unprecedented for an interlocked host system. 

PMID- 25573516
TI  - Reducing CKD risks among vulnerable populations in primary care.
AB  - Ethnic/racial and socioeconomic status disparities in the health-care and
      clinical outcomes of patients with chronic kidney disease (CKD) are pervasive.
      The vast majority of care to decrease incidence of CKD risk and progression
      occurs in primary care settings. High-quality primary care, therefore, represents
      a key strategy through which disparities in the incidence and progression of CKD
      may be eliminated. The Chronic Care Model provides a framework for the delivery
      of high-quality primary care for chronic diseases, and it is frequently used to
      guide health-care quality improvement initiatives. Evidence suggests that Chronic
      Care Model constructs, including provider and organizational quality improvement
      initiatives focused on team approaches to chronic care (eg, case management,
      community health workers), are effective in modifying patients' CKD risks among
      ethnic minority and low-income patients. Other Chronic Care Model constructs,
      including clinical information systems (eg, disease registries), decision support
      interventions, and the provision of patient-centered care have been shown to
      improve processes related to CKD care but with limited and/or mixed effects on
      patient outcomes. Few studies have examined the effect of these approaches on
      reducing disparities. Research is needed to examine the effectiveness of these
      strategies to eliminate CKD disparities among vulnerable populations. 

PMID- 25573518
TI  - Overexpression of RhoGDI2 correlates with the progression and prognosis of
      pancreatic carcinoma.
AB  - Rho GDP dissociation inhibitor 2 (RhoGDI2) has been found to be a regulator of
      tumor metastasis. However, the expression of RhoGDI2 and its clinicopathological
      significance as well as the pathway of RhoGDI2 in tumor metastasis have yet to be
      investigated. To investigate the role of RhoGDI2 in the progression and prognosis
      of pancreatic carcinoma (PC), the expression of RhoGDI2 in human PC tissues was
      examined and compared with the clinicopathological characteristics and prognosis.
      Moreover, the relationship between RhoGDI2 and E-cadherin was examined. The
      results indicated that RhoGDI2 was overexpressed in PC tissues and associated
      with clinicopathological characteristics, including clinical stage and lymph node
      metastasis. Patients with a RhoGDI2-negative expression had a significantly
      longer survival time than those with a RhoGDI2-positive expression. Additionally,
      the expression of RhoGDI2 was negatively correlated with the expression of E
      cadherin in PC tissues. Taken together, the findings suggest that RhoGDI2 is
      important in the progression and prognosis of PC, and may be used as a potential
      prognostic biomarker and a therapeutic target for PC.

PMID- 25573519
TI  - Enantioselective formal [3+3] cycloadditions of ketones and cyclic 1-azadienes by
      cascade enamine-enamine catalysis.
AB  - An asymmetric formal [3+3] cycloaddition process with diversely structured
      aliphatic ketones and electron-deficient cyclic 1-azadienes was developed by
      cascade enamine-enamine catalysis of a cinchona-based primary amine. This
      sequence involved a domino Michael addition-Mannich reaction to afford
      spirocyclic architectures in excellent diastereo- and enantioselectivity.
      Importantly, high regioselectivity was realized for a number of unsymmetrical
      aliphatic ketone substrates. 

PMID- 25573520
TI  - Increased utilisation of primary healthcare in persons exposed to severe stress
      in prenatal life: a national population-based study in Denmark.
AB  - OBJECTIVE: Recent studies have suggested that stress in a pregnant mother may
      affect the future health of the unborn child negatively. An excellent proxy for
      health problems is the use of healthcare resources. Using nationwide data, we
      examined whether persons born to mothers who lost a close relative during
      pregnancy have more contacts to general practice. DESIGN: Population-based cohort
      study. SETTING: Denmark. PARTICIPANTS: We included all children born in Denmark
      from 1973 to 2002 (N=2 032 528). Exposure of prenatal stress was defined as
      maternal bereavement by the death of a close relative during the antenatal
      period. The outcome of interest was contact with general practice between 2003
      and 2009 when the participants were between 1 and 35 years of age. Poisson
      regression was used to assess the association between exposure and outcome.
      OUTCOME MEASURES: Contacts to general practitioner. RESULTS: Overall, persons
      exposed to prenatal stress had 2% more GP contacts than those not exposed,
      primarily due to increased utilisation of healthcare services during late
      adolescence and early adulthood. The exposed persons born to mothers who had lost
      a spouse had a higher risk (relative risk (RR) 1.12, 95% CI 1.10 to 1.14) and so
      did those born to mothers who had lost a close relative due to unexpected death
      (RR 1.06, 95% CI 1.05 to 1.06). Exposed persons had more contacts to general
      practice in daytime and more psychometric tests, talk therapies and C reactive
      protein tests than unexposed persons. CONCLUSIONS: Prenatal stress following
      maternal bereavement was associated with a slightly increased utilisation of
      primary healthcare, mainly due to increased healthcare needs related to mental
      health and infections. Understanding how stress during pregnancy influences the
      future health of the child is an important aspect of prenatal care.

PMID- 25573521
TI  - Methadone maintenance treatment programme reduces criminal activity and improves
      social well-being of drug users in China: a systematic review and meta-analysis.
AB  - OBJECTIVE: Methadone maintenance treatment (MMT) has been implemented in China
      since 2004 and has expanded into a nationwide programme. This study aims to
      evaluate changes in social functioning, family relations and drug-related
      criminal behaviour among MMT clients in China. DESIGN: Systematic review and meta
      analysis. METHODS: Both English and Chinese literature databases, including
      PubMed, Chongqing VIP Chinese Science and Technology Journals Database (CQVIP),
      China National Knowledge Infrastructure (CNKI) and Wanfang Data, were
      comprehensively searched over the period 2004-2014 for studied indicators. Study
      selection, quality assessment and data extraction were conducted according to the
      PRISMA (preferred reporting items for systematic reviews and meta-analyses)
      Statement. Meta-analyses were conducted using Comprehensive Meta-Analysis Biostat
      software. RESULTS: Thirty-eight articles were included in this review (1 in
      English and 37 in Chinese). The self-reported arrest rate decreased from 13.1%
      (95% CI 9.1% to 18.5%) at baseline to 3.4% (95% CI 1.5% to 7.7%) and 4.3% (95% CI
      1.6% to 11.4%) after 6 and 12 months of MMT intervention, respectively. The rate
      of drug selling decreased from 7.6% (95% CI 3.8% to 14.8%) at baseline to 1.9%
      (95% CI 0.6% to 6.2%) and 3.0% (95% CI 1.0% to 8.9%) after 6 and 12 months of
      intervention, respectively. Similarly, the rates of selling sex for drugs and
      drug-related crime decreased from 5.3% (95% CI 2.4% to 11.1%) and 9.9% (95% CI
      6.8% to 14.2%) at baseline to 1.1% (95% CI 0.5% to 2.3%) and 3.4% (95% CI 2.5% to
      4.5%) at 6 months, then to 0.8% (95% CI 0.3% to 1.9%) and 3.4% (95% CI 0.8% to
      13.1%) at 12 months after treatment initiation, respectively. In contrast, the
      rate of employment of clients and the proportion of clients having a good
      relationship with their family increased substantially from 26.4% (95% CI 22.9%
      to 30.1%) and 37.9% (95% CI 32.0% to 44.2%) to 41.6% (95% CI 36.6% to 48.0%) and
      59.6% (95% CI 48.1% to 70.2%) at 6 months, then to 59.8% (95% CI 52.4% to 66.8%)
      and 75.0% (95% CI 69.0% to 80.2%) at 12 months after treatment initiation,
      respectively. CONCLUSIONS: MMT has significantly reduced criminal activity, and
      improved employment rate and social well-being, of clients of the MMT programme.
      MMT is an effective measure to help drug users to resume societal and familial
      functions in China.

PMID- 25573522
TI  - An emerging evidence base for PET-CT in the management of childhood
      rhabdomyosarcoma: systematic review.
AB  - INTRODUCTION: Rhabdomyosarcoma (RMS) management depends on risk stratification at
      diagnosis and treatment response. Assessment methods include CT, MRI, bone
      scintigraphy, histological analysis and bone marrow biopsy. Advanced functional
      imaging (FI) has potential to improve staging accuracy and management strategies.
      METHODS AND ANALYSIS: We conducted a systematic review (PROSPERO
      2013:CRD42013006128) of diagnostic accuracy and clinical effectiveness of FI in
      histologically proven paediatric RMS. PRISMA guidance was followed. We searched
      10 databases to November 2013. Studies with >=10 patients with RMS which compared
      positron emission tomography (PET), PET-CT or diffusion-weighted imaging (DWI)
      MRI to conventional imaging at any treatment stage were included. Study quality
      was assessed. Limited, heterogeneous effectiveness data required narrative
      synthesis, illustrated by plotting sensitivity and specificity in receiver
      operating curve (ROC) space. RESULTS: Eight studies (six PET-CT, two PET) with
      272 RMS patients in total were included. No DWI-MRI studies met inclusion
      criteria. Pooled estimates were not calculated due to sparseness of data. Limited
      evidence indicated initial PET-CT results were predictive of survival. PET-CT
      changed management of 7/40 patients. Nodal involvement PET-CT: sensitivity ranged
      from 80% to 100%; specificity from 89% to 100%. Distant metastatic involvement:
      PET-CT sensitivity ranged from 95% to 100%; specificity from 80% to100%. Data on
      metastases in different sites were sparse. Limited data were found on outcome
      prediction by PET-CT response. DISSEMINATION AND ETHICS: PET/PET-CT may increase
      initial staging accuracy in paediatric RMS, specifically in the detection of
      nodal involvement and distant metastatic spread. There is a need to further
      assess PET-CT for this population, ideally in a representative, unbiased and
      transparently selected cohort of patients.

PMID- 25573523
TI  - Childbirth, hospitalisation and sickness absence: a study of female twins.
AB  - OBJECTIVE: To investigate associations of giving birth with morbidity in terms of
      hospitalisation and social consequences of morbidity in terms of sickness absence
      (SA), while taking familial (genetics and shared environmental) factors into
      account. DESIGN: Prospective register-based cohort study. Estimates of risk of
      hospitalisation and SA were calculated as HRs with 95% CIs. SETTING: All female
      twins, that is, women with a twin sister, born in Sweden. PARTICIPANTS: 5118
      Swedish female twins (women with a twin sister), born during 1959-1990, where at
      least one in the twin pair had their first childbirth (T0) during 1994-2009 and
      none gave birth before 1994. MAIN OUTCOME MEASURES: Hospitalisation and SA during
      year 3-5 after first delivery or equivalent. RESULTS: Preceding the first
      childbirth, the mean annual number of SA days increased for mothers, and then
      decreased again. Hospitalisation after T0 was associated with higher HRs of short
      term and long-term SA (HR for short-term SA 3.0; 95% CI 2.5 to 3.6 and for long
      term SA 2.3; 95% CI 1.6 to 3.2). Hospitalisation both before and after first
      childbirth was associated with a higher risk of future SA (HR for long-term SA
      4.2; 95% CI 2.7 to 6.4). Familial factors influenced the association between
      hospitalisation and long-term SA, regardless of childbirth status. CONCLUSIONS:
      Women giving birth did not have a higher risk for SA than those not giving birth
      and results indicate a positive health selection into giving birth. Mothers
      hospitalised before and/or after giving birth had higher risks for future SA,
      that is, there was a strong association between morbidity and future SA.

PMID- 25573524
TI  - Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis
      registry: a cross-sectional survey.
AB  - OBJECTIVES: (1)To describe the prevalence and severity of tremor in patients with
      multiple sclerosis (MS) registered within a large North American MS registry; (2)
      to provide detailed descriptions on the characteristics and severity of tremor in
      a subset of registrants and (3) to compare several measures of tremor severity
      for strength of agreement. SETTING: The North American Research Committee on MS
      (NARCOMS) registry. PARTICIPANTS: Registrants of NARCOMS reporting mild or
      greater tremor severity. OUTCOME MEASURES: We determined the cross-sectional
      prevalence of tremor in the NARCOMS registry over three semiannual updates
      between fall 2010 and fall 2011. A subset of registrants (n=552) completed a
      supplemental survey providing detailed descriptions of their tremor. Outcomes
      included descriptive characteristics of their tremors and correlations between
      outcome measures to determine the strength of agreement in assessing tremor
      severity. RESULTS: The estimated prevalence of tremor in NARCOMS ranged from 45%
      to 46.8%, with severe tremor affecting 5.5-5.9% of respondents. In the subset
      completing the supplemental survey, mild tremor severity was associated with
      younger age of MS diagnosis and tremor onset than those with moderate or severe
      tremor. However, tremor severity did not differ by duration of disease or tremor.
      Respondents provided descriptions of tremor symptoms on the Clinical Ataxia
      Rating Scale, which had a moderate to good (rho=0.595) correlation with the
      Tremor Related Activities of Daily Living (TRADL) scale. Objectively scored
      Archimedes' spirals had a weaker (rho=0.358) correlation with the TRADL. Rates of
      unemployment, disability and symptomatic medication use increased with tremor
      severity, but were high even among those with mild tremor. CONCLUSIONS: Tremor is
      common among NARCOMS registrants and severely disabling for some. Both ADL-based
      and symptom-descriptive measures of tremor severity can be used to stratify
      patients.

PMID- 25573525
TI  - Acupuncture for adults with overactive bladder: a systematic review protocol.
AB  - INTRODUCTION: Overactive bladder (OAB) is a symptom syndrome defined by the
      International Continence Society (ICS) as 'the presence of urinary urgency (both
      daytime and nighttime), usually accompanied by increased frequency and nocturia
      with or without urge urinary incontinence in the absence of a urinary tract
      infection or other obvious pathology'. Clinical studies indicate that acupuncture
      could reduce micturition over 24 h, urgency episodes over 24 h, and improve
      quality of life among people with OAB. This systematic review protocol details
      the proposed methods for evaluating the effectiveness and safety of acupuncture
      for OAB. METHODS AND ANALYSIS: The following databases will be searched for
      relevant studies: the Cochrane Central Register of Controlled Trials (CENTRAL),
      the Cochrane Incontinence Group Trials Register, MEDLINE, EMBASE, Chinese
      Biomedical Literature Database (CBM), Chinese Medical Current Content (CMCC),
      Chinese Scientific Journal Database (VIP database), Wan-Fang Data, and China
      National Knowledge Infrastructure (CNKI) and will hand search a list of medical
      journals as a supplement. Any randomised controlled trials in English or Chinese
      without restriction of publication status will be included with treatment of OAB.
      Outcomes will mainly include number of micturition episodes over 24 h, number of
      urgency episodes over 24 h and number of incontinence episodes over 24 h. Two
      reviewers will independently screen the titles, abstracts or even full texts, and
      extract data. Two other reviewers will assess study quality. Revman 5.1 software
      will be used to conduct meta-analysis and calculate the risk ratio for
      dichotomous data. Weighted mean difference or standard mean difference will be
      calculated for continuous data. The Cochrane collaboration's tool will be used to
      assess the risk of bias. DISSEMINATION: This systematic review protocol will
      provide information on acupuncture therapy for OAB. The results will be
      disseminated through peer-reviewed publication or conference presentations.
      PROTOCOL REGISTRATION: PROSPERO CRD42014010181.

PMID- 25573526
TI  - Healthy Start vitamins--a missed opportunity: findings of a multimethod study.
AB  - OBJECTIVE: To evaluate and provide a real-life view of the operation of the
      Healthy Start vitamins scheme. SETTING: The study took place in primary care and
      community settings that served rural, urban and ethnically diverse populations,
      in two sentinel sites: London, and Yorkshire and the Humber. An online
      consultation and stakeholder workshops elicited views from across England.
      PARTICIPANTS: 669 health and social care practitioners including health visitors,
      midwives, public health practitioners, general practitioners, paediatricians and
      support staff participated in focus group discussions (n=49) and an online
      consultation (n=620). 56 participants representing health and social care
      practitioners, policymakers, service commissioners, and voluntary and independent
      sectors took part in stakeholder workshops. METHODS: Three-phase multimethod
      study comprising focus group discussions, an online consultation and stakeholder
      workshops. Qualitative data were analysed thematically and quantitative data from
      the online survey were analysed using descriptive statistics. RESULTS: Study
      participants were concerned about the low uptake of Healthy Start vitamin
      supplements and the consequences of this for health outcomes for women and young
      children. They experienced Healthy Start vitamin distribution as logistically
      complex, requiring the time, resources and creative thinking of a range of local
      and regional practitioners from senior strategists to administrative support
      workers. In the light of this, many participants argued that moving to universal
      provision of vitamin supplements would be more cost-effective than the current
      system. CONCLUSIONS: There is consistency of views of health practitioners that
      the current targeted system of providing free vitamin supplements for low-income
      childbearing women and young children via the Healthy Start programme is not
      fulfilling its potential to address vitamin deficiencies. There is wide
      professional and voluntary sector support for moving from the current targeted
      system to provision of free vitamin supplements for all pregnant and new mothers,
      and children up to their fifth birthday.

PMID- 25573528
TI  - Antibody activation using DNA-based logic gates.
AB  - Oligonucleotide-based molecular circuits offer the exciting possibility to
      introduce autonomous signal processing in biomedicine, synthetic biology, and
      molecular diagnostics. Here we introduce bivalent peptide-DNA conjugates as
      generic, noncovalent, and easily applicable molecular locks that allow the
      control of antibody activity using toehold-mediated strand displacement
      reactions. Employing yeast as a cellular model system, reversible control of
      antibody targeting is demonstrated with low nM concentrations of peptide-DNA
      locks and oligonucleotide displacer strands. Introduction of two different
      toehold strands on the peptide-DNA lock allowed signal integration of two
      different inputs, yielding logic OR- and AND-gates. The range of molecular inputs
      could be further extended to protein-based triggers by using protein-binding
      aptamers. 

PMID- 25573529
TI  - CD44v6 promotes beta-catenin and TGF-beta expression, inducing aggression in
      ovarian cancer cells.
AB  - A high expression of CD44v6 has been reported in numerous malignant cancers,
      including stomach, prostate, lung and colon. However, the pathological role and
      the regulatory mechanisms of CD44v6 have yet to be elucidated. In the present
      study, the expression levels of CD44v6 were shown to be significantly higher in
      ovarian cancer tissues, as compared with adjacent normal tissues. Furthermore,
      the upregulated expression levels of CD44v6 were correlated with disease
      recurrence and poor survival in patients. The expression of CD44v6 was knocked
      down in the CAOV3 ovarian cell line, by transfection of a specific small hairpin
      RNA. The present study showed a correlation between the aggression, viability,
      invasion and migration of the ovarian cancer cells, with the expression of
      CD44v6. In addition, the expression of CD44v6 was positively correlated with the
      expression levels of beta-catenin and tumor growth factor-beta, which indicates
      that the effects of CD44v6 on ovarian cancer cell aggression may be mediated by
      these two signaling pathways. In conclusion, the present study provides a novel
      insight into the association between CD44v6 expression and ovarian cancer. CD44v6
      may provide a novel target for the prognosis and treatment of ovarian cancer.

PMID- 25573527
TI  - Japanese POEMS syndrome with Thalidomide (J-POST) Trial: study protocol for a
      phase II/III multicentre, randomised, double-blind, placebo-controlled trial.
AB  - INTRODUCTION: Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin
      changes (POEMS) syndrome is a fatal systemic disorder associated with plasma cell
      dyscrasia and the overproduction of the vascular endothelial growth factor
      (VEGF). Recently, the prognosis of POEMS was substantially improved by
      introduction of therapeutic intervention for myeloma. However, no randomised
      clinical trial has been performed because of the rarity and severity of the
      disease. METHODS AND ANALYSIS: The Japanese POEMS syndrome with Thalidomide (J
      POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled
      trial that aims to evaluate the efficacy and safety of a 24-week treatment with
      thalidomide in POEMS syndrome, with an additional 48-week open-label safety
      study. Adults with POEMS syndrome who have no indication for transplantation are
      assessed for eligibility at 12 tertiary neurology centres in Japan. Patients who
      satisfy the eligibility criteria are randomised (1:1) to receive thalidomide (100
      300 mg daily) plus dexamethasone (12 mg/m(2) on days 1-4 of a 28-day cycle) or
      placebo plus dexamethasone. Both treatments were administered for 24 weeks (six
      cycles; randomised comparative study period). Patients who complete the
      randomised study period or show subacute deterioration during the randomised
      period participate in the subsequent 48-week open-label safety study (long-term
      safety period). The primary end point of the study is the reduction rate of serum
      VEGF levels at 24 weeks. ETHICS AND DISSEMINATION: The protocol was approved by
      the Institutional Review Board of each hospital. The trial was notified and
      registered at the Pharmaceutical and Medical Devices Agency, Japan (No. 22-1716).
      The J-POST Trial is currently ongoing and is due to finish in August 2015. The
      findings of this trial will be disseminated through peer-reviewed publications
      and conference presentations and will also be disseminated to participants. TRIAL
      REGISTRATION NUMBER: UMIN000004179 and JMA-IIA00046.

PMID- 25573530
TI  - Characterization of efficiency-limiting resistance losses in monolithically
      integrated Cu(In,Ga)Se2 solar modules.
AB  - The cell-to-module efficiency gap in Cu(In,Ga)Se2 (CIGS) monolithically
      integrated solar modules is enhanced by contact resistance between the Al-doped
      ZnO (AZO) and Mo back contact layers, the P2 contact, which connects adjacent
      cells. The present work evaluated the P2 contact resistance, in addition to the
      TCO resistance, using an embedded transmission line structure in a commercial
      grade module without using special sample fabrication methods. The AZO layers
      between cells were not scribed; instead, the CIGS/CdS/i-ZnO/AZO device was
      patterned in a long stripe to permit measurement of the Mo electrode pair
      resistance over current paths through two P2 contacts (Mo/AZO) and along the AZO
      layer. The intercept and slope of the resistance as a function of the electrode
      interval yielded the P2 contact resistance and the TCO resistance, respectively.
      Calibration of the parasitic resistances is discussed as a method of improving
      the measurement accuracy. The contribution of the P2 contact resistance to the
      series resistance was comparable to that of the TCO resistance, and its origin
      was attributed to remnant MoSe2 phases in the P2 region, as verified by
      transmission electron microscopy. 

PMID- 25573531
TI  - Palliative care and quality of life for people with dementia: medical and
      psychosocial interventions.
AB  - BACKGROUND: Despite mounting evidence that principles of palliative care are
      appropriate in care for individuals with dementia they are often not applied. As
      a result, patients with dementia are often exposed to burdensome interventions
      that have little or no benefit and are not provided with psychosocial treatments.
      METHODS: Recommendations for applying palliative care principles in caring for
      people with dementia are provided, based on the WHO definition of palliative
      care, our clinical experience and some key literature reports. RESULTS: People
      with a diagnosis of an irreversible dementia such as Alzheimer's disease (AD) and
      their families are rarely informed that this is a terminal disease and palliative
      care principles are not discussed with them. They are applicable early in the
      course of illness when the person can still make end-of-life decisions.
      Palliative care can be used in conjunction with other therapies and services,
      such as hospice care that provide relief from pain and other distressing
      symptoms. The care should include keeping people with dementia involved in
      meaningful activities which decrease or eliminate behavioral symptoms of
      dementia. CONCLUSIONS: Educating families and professionals about palliative care
      is important as many professionals and non-professionals believe that this
      approach intends to hasten death, instead of affirming life and regarding dying
      as a normal process. Living, not just existing, with a dementing illness involves
      encouraging the person to continue to be involved in meaningful activities.
      Medical interventions should be compatible with goals of care and balance
      benefits and burdens for each intervention taking into consideration severity of
      dementia.

PMID- 25573532
TI  - Descriptive epidemiology of domain-specific sitting in working adults: the
      Stormont Study.
AB  - BACKGROUND: Given links between sedentary behaviour and unfavourable health
      outcomes, there is a need to understand the influence of socio-demographic
      factors on sedentary behaviour to inform effective interventions. This study
      examined domain-specific sitting times reported across socio-demographic groups
      of office workers. METHODS: The analyses are cross-sectional and based on a
      survey conducted within the Stormont Study, which is tracking employees in the
      Northern Ireland Civil Service. Participants self-reported their daily sitting
      times across multiple domains (work, TV, travel, PC use and leisure) on workdays
      and non-workdays, along with their physical activity and socio-demographic
      variables (sex, age, marital status, BMI, educational attainment and work
      pattern). Total and domain-specific sitting on workdays and non-workdays were
      compared across socio-demographic groups using multivariate analyses of
      covariance. RESULTS: Completed responses were obtained from 4436 participants.
      For the whole sample, total daily sitting times were higher on workdays in
      comparison to non-workdays (625 +/- 168 versus 469 +/- 210 min/day, P < 0.001).
      On workdays and non-workdays, higher sitting times were reported by individuals
      aged 18-29 years, obese individuals, full-time workers and
      single/divorced/widowed individuals (P < 0.001). CONCLUSIONS: Interventions are
      needed to combat the high levels of sedentary behaviour observed in office
      workers, particularly among the highlighted demographic groups. Interventions
      should target workplace and leisure-time sitting.

PMID- 25573533
TI  - Phase I study of olaparib plus gemcitabine in patients with advanced solid
      tumours and comparison with gemcitabine alone in patients with locally
      advanced/metastatic pancreatic cancer.
AB  - BACKGROUND: Olaparib (Lynparza) is an oral poly(adenosine diphosphate [ADP]
      ribose) polymerase inhibitor that induces synthetic lethality in cancers with
      homologous recombination defects. PATIENTS AND METHODS: In this phase I, dose
      escalation trial, patients with advanced solid tumours received olaparib (50-200
      mg capsules b.i.d.) continuously or intermittently (days 1-14, per 28-day cycle)
      plus gemcitabine [i.v. 600-800 mg/m(2); days 1, 8, 15, and 22 (cycle 1), days 1,
      8, and 15 (subsequent cycles)] to establish the maximum tolerated dose. A
      separate dose-escalation phase evaluated olaparib in tablet formulation (100 mg
      o.d./b.i.d.; days 1-14) plus gemcitabine (600 mg/m(2)). In an expansion phase,
      patients with genetically unselected locally advanced or metastatic pancreatic
      cancer were randomised 2 : 1 to the tolerated olaparib capsule combination dose
      or gemcitabine alone (1000 mg/m(2)). RESULTS: Sixty-six patients were treated
      [dose-escalation phase, n = 44 (tablet cohort, n = 12); dose-expansion phase, n =
      22 (olaparib plus gemcitabine, n = 15; gemcitabine alone, n = 7)]. In the dose
      escalation phase, four patients (6%) experienced dose-limiting toxicities (raised
      alanine aminotransferase, n = 2; neutropenia, n = 1; febrile neutropenia, n = 1).
      Grade >=3 adverse events were reported in 38/47 patients (81%) treated with
      olaparib capsules plus gemcitabine; most common were haematological toxicities
      (55%). Tolerated combinations were olaparib 100 mg b.i.d. capsule
      (intermittently, days 1-14) plus gemcitabine 600 mg/m(2) and olaparib 100 mg o.d.
      tablet (intermittently, days 1-14) plus gemcitabine 600 mg/m(2). There were no
      differences in efficacy observed during the dose-expansion phase. CONCLUSIONS:
      Olaparib 100 mg b.i.d. (intermittent dosing; capsules) plus gemcitabine 600
      mg/m(2) is tolerated in advanced solid tumour patients, with no
      unmanageable/unexpected toxicities. Continuous dosing of olaparib or combination
      with gemcitabine at doses >600 mg/m(2) was not considered to have an acceptable
      tolerability profile for further study. CLINICALTRIALSGOV: NCT00515866.

PMID- 25573534
TI  - Mutants of Micromonospora viridifaciens sialidase have highly variable activities
      on natural and non-natural substrates.
AB  - This study aimed to improve the hydrolase activity of the well-characterised
      bacterial sialidase from Micromonospora viridifaciens. The enzyme and its mutated
      versions were produced in Bacillus subtilis and secreted to the growth medium.
      Twenty amino acid positions in or near the active site were subjected to site
      saturation mutagenesis and evaluated on the artificial sialidase substrate 2-O-(p
      nitrophenyl)-alpha-d-N-acetylneuraminic acid and on the natural substrate casein
      glycomacropeptide. A considerably higher fraction of the mutants exhibited
      increased activity on the artificial substrate compared with the natural one,
      with the most proficient mutant showing a 13-fold improvement in kcat/Km. In
      contrast, no mutants displayed more than a 2-fold increase in activity on the
      natural substrate. To gain further insight into this important discrepancy, we
      analysed the stability of mutants using the PoPMuSiC software, a property that
      also correlates with the potential for introducing chemical variation, after
      validating the method with a set of experimental stability estimates. We found a
      significant correlation between improved hydrolase activity on the artificial
      substrate and reduced apparent stability. Together with the minor improvement on
      the natural substrate this shows an important difference between naturally
      evolved functionality and new laboratory functionality. Our results suggest that
      when engineering sialidases and potentially other proteins towards non-natural
      substrates that are not optimized by natural evolution, major changes in chemical
      properties are advantageous, and these changes tend to correlate with decreased
      stability, partly explaining commonly observed trade-offs between stability and
      proficiency. 

PMID- 25573535
TI  - Novel designs of single-chain MHC I/peptide complex for the magnetosome display
      system.
AB  - The magnetic nanoparticles displaying the class I major histocompatibility
      complex (MHC I) were biologically synthesized using the magnetotactic bacterium
      Magnetospirillum magneticum AMB-1. Expression level and antigen peptide (HER263
      71)-binding capability of the MHC I were evaluated on bacterial magnetic
      particles (BacMPs, also known as magnetosomes). Furthermore, the single-chain
      complexes of MHC I and HER263-71 were de novo designed for the magnetosome
      display system in order to improve the interaction between MHC I and HER263-71.
      Two types of the fusion arrangements were tested, and one of the complexes was
      estimated to fold into the correct conformation at the level of over 70%. In
      addition to the high folding ratio, an advantage of this system is that any
      refolding processes were not required even though the N-terminus of HER263-71
      peptide is not free, which conventional bacterial expression systems have never
      demonstrated. The as-prepared single-chain MHC I/HER263-71 complex-displaying
      BacMPs (MHC I/HER2-BacMPs) specifically interacted with, and magnetically
      separated the HER263-71-induced cells, suggesting that the native T-cell receptor
      could recognize the engineered MHC I/HER2 complex on the BacMPs. By optimizing
      the magnetic sorting method, the MHC I/HER2-BacMPs developed in this study would
      be useful in immunotherapeutic applications. 

PMID- 25573536
TI  - How to interpret serum levels of beta-glucan for the diagnosis of invasive fungal
      infections in adult high-risk hematology patients: optimal cut-off levels and
      confounding factors.
AB  - Detection of the fungal cell wall component beta-glucan (BG) in serum is
      increasingly used to diagnose invasive fungal infections (IFI), but its optimal
      use in hematology patients with high risk of IFI is not well defined. We
      retrospectively analyzed the diagnostic accuracy, optimal cut-off level, and
      potential confounding factors of BG reactivity. The inclusion criteria were:
      adult patients with hematologic disease who were admitted to the hematology ward
      during the 2-year study period and who had two or more consecutive BG assays
      performed. In total, 127 patients were enrolled. Thirteen patients with proven or
      probable IFI, as defined by the 2008 European Organization for Research and
      Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, were identified.
      Receiver operating characteristic (ROC) curve analysis showed a high overall
      diagnostic performance (area under the ROC curve = 0.98) and suggested an optimal
      cut-off level of 158 pg/ml, with a sensitivity and a specificity of 92 % and 96
      %, respectively. Multiway analysis of variance indicated that treatment with
      pegylated asparaginase (p < 0.001), admission to the intensive care unit (ICU; p
      = 0.0007), and treatment with albumin, plasma, or coagulation factors (p = 0.01)
      are potential confounding factors of BG reactivity. We propose that a higher cut
      off level than that recommended by the manufacturer should be used to monitor
      adult hematology patients at high risk for IFI. Our results also suggest that
      elevated BG levels in patients treated with pegylated asparaginase, albumin,
      plasma, or coagulation factors, or those admitted to the ICU should be
      interpreted with caution. 

PMID- 25573537
TI  - Antidiabetic treatment patterns in a medicare advantage population in the United
      States.
AB  - BACKGROUND: Published guidelines for treatment of type 2 diabetes mellitus (T2DM)
      agree on initial pharmacotherapy. However, few specific recommendations on second
      line agents are provided. OBJECTIVE: The objective of this study was to describe
      antidiabetic treatment patterns in Medicare Advantage patients with T2DM within 6
      months of measurement of the glycosylated hemoglobin (HbA1c) level. RESEARCH
      DESIGN: This retrospective cross-sectional study utilized medical, pharmacy, and
      laboratory claims from a large Medicare Advantage with Prescription Drug (MAPD)
      coverage payer. MAPD members between 65 and 89 years old identified as having
      T2DM between 2009 and 2011 were eligible for inclusion. A 12-month baseline
      period before the first HbA1c value (index date) was evaluated for demographic
      and clinical differences. Antidiabetic therapy was evaluated for 6 months post
      index. The study population was stratified into three cohorts based on index
      HbA1c value: controlled (<8%, 64 mmoL/mol), uncontrolled (>= 8%, 64 mmoL/mol and
      <10%, 86 mmoL/mol), and severely uncontrolled (>= 10%, 86 mmoL/mol). RESULTS:
      Despite elevated HbA1c values (>= 8%, 64 mmoL/mol), 7-8% of patients did not
      receive antidiabetic therapy during the post-index period. Metformin and
      sulfonylureas were the oral antidiabetics (OADs) most frequently used as
      monotherapy. The majority of patients on combination therapy were on two or more
      OADs and higher injectable use was observed in the severely uncontrolled cohort.
      Metformin was included in >60% of the combination regimens with metformin +
      sulfonylurea being the most common. CONCLUSION: This study suggests suboptimal
      treatment of those not in glycemic control (HbA1c >= 8%, 64 mmoL/mol). Many
      patients classified as severely uncontrolled based on HbA1c received only
      monotherapy. Opportunities exist for treatment modification within this
      population to achieve tighter glycemic control.

PMID- 25573538
TI  - Pharmacological management of behavioral and psychiatric symptoms in older adults
      with intellectual disability.
AB  - Given medical and social advances, the life expectancy of individuals with
      intellectual disability (ID) has increased dramatically, leading to a generation
      of older individuals with such disabilities. This review focuses on the
      pharmacological treatment of behavioral and psychiatric symptoms and disorders in
      older adults with ID. Older adults with ID often present with medical co
      morbidities and mental health issues. Medication management of behavioral and
      psychiatric problems is complicated by a higher risk for adverse events, lack of
      decision-making capacity, and complex care networks. Some studies have shown that
      individuals with ID and co-morbid mental disorders are undertreated in comparison
      with those with similar disorders in the general population, resulting in poorer
      outcomes. However, older adults with ID are also at risk of polypharmacy, and
      older age is a risk factor for development of side effects. A general principle
      is that medication treatment for psychiatric disorders in older individuals with
      ID should be started at low dosages and increased cautiously while monitoring
      response and side effects. The use of psychotropic drugs for older individuals
      with ID and behavioral problems remains controversial, particularly in those with
      dementia. 

PMID- 25573540
TI  - The effect of intravenous sulfobutylether7 -beta-cyclodextrin on the
      pharmacokinetics of a series of adamantane-containing compounds.
AB  - Intravenously administered (i.v.) drug-cyclodextrin (CD) inclusion complexes are
      generally expected to dissociate rapidly and completely, such that the i.v.
      pharmacokinetic profile of a drug is unchanged in the presence of CD. The altered
      pharmacokinetics of a synthetic ozonide in rats has been attributed to an
      unusually high-binding affinity (2.3 * 10(6) M(-1) ) between the drug and
      sulfobutylether7 -beta-cyclodextrin (SBE7 -beta-CD) with further studies
      suggesting a significant binding contribution from the adamantane ring. This work
      investigated the binding affinity of three adamantane derivatives [amantadine
      (AMA), memantine (MEM) and rimantadine (RIM)] to SBE7 -beta-CD and the impact of
      complexation on their i.v. pharmacokinetics. In vitro studies defined the plasma
      protein binding, as well as the impact of SBE7 -beta-CD on erythrocyte
      partitioning of each compound. SBE7 -beta-CD binding constants for the compounds
      were within the typical range for drug-like molecules (10(2) -10(4) M(-1) ). The
      pharmacokinetics of AMA and MEM were unchanged; however, significant alteration
      of RIM plasma and urinary pharmacokinetics was observed when formulated with CD.
      In vitro studies suggested two factors contributing to the altered
      pharmacokinetics: (1) low plasma protein binding of RIM, and (2) decreased
      erythrocyte partitioning in the presence of high SBE7 -beta-CD concentrations.
      This work demonstrated the potential for typical drug-cyclodextrin interactions
      to alter drug plasma pharmacokinetics.

PMID- 25573539
TI  - Anthocyanins do not influence long-chain n-3 fatty acid status: studies in cells,
      rodents and humans.
AB  - Increased tissue status of the long-chain n-3 polyunsaturated fatty acids (LC n-3
      PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) is associated with
      cardiovascular and cognitive benefits. Limited epidemiological and animal data
      suggest that flavonoids, and specifically anthocyanins, may increase EPA and DHA
      levels, potentially by increasing their synthesis from the shorter-chain n-3
      PUFA, alpha-linolenic acid. Using complimentary cell, rodent and human studies we
      investigated the impact of anthocyanins and anthocyanin-rich foods/extracts on
      plasma and tissue EPA and DHA levels and on the expression of fatty acid
      desaturase 2 (FADS2), which represents the rate limiting enzymes in EPA and DHA
      synthesis. In experiment 1, rats were fed a standard diet containing either palm
      oil or rapeseed oil supplemented with pure anthocyanins for 8 weeks.
      Retrospective fatty acid analysis was conducted on plasma samples collected from
      a human randomized controlled trial where participants consumed an elderberry
      extract for 12 weeks (experiment 2). HepG2 cells were cultured with alpha
      linolenic acid with or without select anthocyanins and their in vivo metabolites
      for 24 h and 48 h (experiment 3). The fatty acid composition of the cell
      membranes, plasma and liver tissues were analyzed by gas chromatography.
      Anthocyanins and anthocyanin-rich food intake had no significant impact on EPA or
      DHA status or FADS2 gene expression in any model system. These data indicate
      little impact of dietary anthocyanins on n-3 PUFA distribution and suggest that
      the increasingly recognized benefits of anthocyanins are unlikely to be the
      result of a beneficial impact on tissue fatty acid status. 

PMID- 25573542
TI  - Obesity and its association with comorbidities and hospital charges among
      patients hospitalized for dental conditions.
AB  - AIM: The aim of the present study was to examine the impact of obesity on
      hospitalization charges and comorbid burden following hospitalization due to
      dental conditions. METHODS: The Nationwide Inpatient Sample for 2004-2010 was
      used. All hospitalizations due to dental conditions were selected. The prevalence
      of obesity was estimated among these hospitalizations. Multivariable linear
      regression models were used to examine the impact of obesity on outcomes.
      RESULTS: A total of 11 965 hospitalizations were attributed to dental conditions;
      5.6% were related to obesity. The proportion of those who were obese increased
      over the study period (ranging from 3.7% in 2004 to 7.3% in 2010). The mean age
      of those who were obese was 45 years (compared to 38.7 years for those who were
      not obese). Close to 41% of those who were obese were males (compared to 51% who
      were not obese). Whites comprised 62.4% of those who were obese (compared to
      59.2% of those who were not obese). Those who were obese had a higher comorbid
      burden compared to those who were not obese (83.5% of those who were obese had at
      least one comorbid condition, whereas 56.4% of those who were not obese had at
      least one comorbid condition). Those who were obese had higher hospitalization
      charges ($US2225 more, P = 0.0001). CONCLUSIONS: Obesity is associated with high
      comorbid burden and hospital charges among patients hospitalized due to dental
      conditions.

PMID- 25573544
TI  - Editorial: new editorial standards to better serve the community.

PMID- 25573543
TI  - Ginsenoside Rb1 inhibits neuronal apoptosis and damage, enhances spinal aquaporin
      4 expression and improves neurological deficits in rats with spinal cord ischemia
      reperfusion injury.
AB  - Ginsenoside Rb1 is a potential therapeutic agent for the treatment of spinal cord
      ischemia-reperfusion injury (SCII), although it has not yet been investigated in
      depth. The aim of the present study was to investigate the effects of ginsenoside
      Rb1 treatment on SCII and aquaporin-4 (AQP4) expression in the rat spinal cord.
      Experimental animals were subjected to one of four conditions, including the
      blank control condition, sham procedure, spinal cord ischemia-reperfusion induced
      by abdominal aortic occlusion or spinal cord ischemia-reperfusion followed by
      ginsenoside Rb1 treatment. Locomotor activity was evaluated using the Basso
      Beattie Bresnahan scale. Spinal cord damage was assessed with hematoxylin and
      eosin and Nissl staining and the apoptotic rate was measured using terminal
      deoxynucleotidyl transferase dUTP nick end labeling. AQP4 expression was assessed
      by immunohistochemical analysis, western blotting and reverse transcription
      quantitative polymerase chain reaction. Abdominal aortic occlusion resulted in
      the reduced expression of AQP4 in the spinal cord, which gradually recovered over
      time. Furthermore, ginsenoside Rb1 treatment significantly attenuated this
      decrease and protected the integrity of and reduced the apoptotic rate in spinal
      cord neurons. Treatment with ginsenoside Rb1 attenuated the initial
      downregulation and advanced the recovery of AQP4 expression levels, suggesting a
      possible mechanism for the therapeutic effects on SCII.

PMID- 25573545
TI  - Communication: fast transport and relaxation of vibrational energy in polymer
      chains.
AB  - We investigate ballistic vibrational energy transport through optical phonon band
      in oligomeric chains in the presence of decoherence. An exact solution is
      obtained for the excitation density in the space-time representation in the
      continuous limit and this solution is used to characterize the energy transport
      time and intensity. Three transport mechanisms are identified such as ballistic,
      diffusive, and directed diffusive regimes, occurring at different distances and
      time scales. The crossover between the two diffusive regimes is continuous, while
      the switch between the ballistic and diffusive mechanisms occurs in a
      discontinuous manner in accord with the recent experimental results on energy
      transport in perfluoroalkanes. 

PMID- 25573541
TI  - Additional bone graft accelerates healing of clavicle non-unions and improves
      long-term results after 8.9 years: a retrospective study.
AB  - BACKGROUND: Clavicle non-unions can occur after both conservative and operative
      treatment failure. Here, we investigated the outcome of patients with delayed
      fracture healing or non-unions of the clavicle. Patients underwent revision
      surgery by plate osteosynthesis of the clavicle with or without bone grafting.
      Our aim was to determine rates of bone healing and the functional long-term
      outcome. METHODS: The study population of 58 consecutive patients was divided
      into group 1 (n = 25; no bone graft) and group 2 (n = 33; iliac crest bone
      graft). Bone consolidation was determined by the Lane-Sandhu score preoperatively
      and after 2.2 +/- 1.8 years, respectively. The functional long-term outcome was
      determined after 8.9 +/- 2.7 years in all available patients (n = 30) by the
      Constant score, DASH (Disabilities of the Arm, Shoulder and Hand) score and SF
      36, and clavicle length was measured by ultrasound as compared to the healthy
      side. RESULTS: Clavicle consolidation was achieved in 54 out of 58 patients
      (93.1%) after revision surgeries. The radiographic score and bone consolidation
      rates were significantly higher in group 2 (93.3%) as compared with 72% in group
      1 (p = 0.02), resulting in a significantly shorter time to bone consolidation in
      group 2. Similarly, the relative risk for additional surgery after the first
      revision surgery was 4.7-fold higher in group 1 (p = 0.02). The long-term results
      showed overall very good results in DASH score (14.9 +/- 16.5) and good results
      in Constant scores (77.9 +/- 19.9). The group analyses found significantly better
      Constant scores and better visual analogue pain scale (VAS) numbers in group 2.
      Clavicle shortening appeared to affect the clinical results, and a mild
      correlation between shortening and Constant scores (R = -0.31) was found.
      CONCLUSIONS: This study shows high rates of bone healing and good functional
      outcomes after surgical revision of clavicle non-unions and further demonstrates
      that additional bone graft could significantly accelerate bone healing. This
      indicates that revision surgery of clavicle non-unions might preferably be done
      with additional bone graft, even if the surgeon considers that bone healing might
      be achieved without bone grafting.

PMID- 25573546
TI  - Communication: kinetics of scavenging of small, nucleating clusters: first
      nucleation theorem and sum rules.
AB  - Despite recent advances in monitoring nucleation from a vapor at close-to
      molecular resolution, the identity of the critical cluster, forming the
      bottleneck for the nucleation process, remains elusive. During past twenty years,
      the first nucleation theorem has been often used to extract the size of the
      critical cluster from nucleation rate measurements. However, derivations of the
      first nucleation theorem invoke certain questionable assumptions that may fail,
      e.g., in the case of atmospheric new particle formation, including absence of sub
      critical cluster losses and heterogeneous nucleation on pre-existing
      nanoparticles. Here, we extend the kinetic derivation of the first nucleation
      theorem to give a general framework to include such processes, yielding sum rules
      connecting the size dependent particle formation and loss rates to the
      corresponding loss-free nucleation rate and the apparent critical size from a
      naive application of the first nucleation theorem that neglects them. 

PMID- 25573547
TI  - Discontinuity of the exchange-correlation potential and the functional derivative
      of the noninteracting kinetic energy as the number of electrons crosses integer
      boundaries in Li, Be, and B.
AB  - Accurate densities were determined from configuration interaction wave functions
      for atoms and ions of Li, Be, and B with up to four electrons. Exchange
      correlation potentials, Vxc(r), and functional derivatives of the noninteracting
      kinetic energy, deltaK[rho]/deltarho(r), obtained from these densities were used
      to examine their discontinuities as the number of electrons N increases across
      integer boundaries for N = 1, N = 2, and N = 3. These numerical results are
      consistent with conclusions that the discontinuities are characterized by a jump
      in the chemical potential while the shape of Vxc(r) varies continuously as an
      integer boundary is crossed. The discontinuity of the Vxc(r) is positive, depends
      on the ionization potential, electron affinity, and orbital energy differences,
      and the discontinuity in deltaK[rho]/deltarho(r) depends on the difference
      between the energies of the highest occupied and lowest unoccupied orbitals. The
      noninteracting kinetic energy and the exchange correlation energy have been
      computed for integer and noninteger values of N between 1 and 4. 

PMID- 25573548
TI  - On the convergence of perturbative coupled cluster triples expansions: error
      cancellations in the CCSD(T) model and the importance of amplitude relaxation.
AB  - Recently, we proposed a novel Lagrangian-based perturbation series-the CCSD(T-n)
      series-which systematically corrects the coupled cluster singles and doubles
      (CCSD) energy in orders of the Moller-Plesset fluctuation potential for effects
      due to triple excitations. In the present study, we report numerical results for
      the CCSD(T-n) series up through fourth order which show the predicted convergence
      trend throughout the series towards the energy of its target, the coupled cluster
      singles, doubles, and triples (CCSDT) model. Since effects due to the relaxation
      of the CCSD singles and doubles amplitudes enter the CCSD(T-n) series at fourth
      order (the CCSD(T-4) model), we are able to separate these effects from the total
      energy correction and thereby emphasize their crucial importance. Furthermore, we
      illustrate how the LambdaCCSD[T]/(T) and CCSD[T]/(T) models, which in slightly
      different manners augment the CCSD energy by the [T] and (T) corrections
      rationalized from many-body perturbation theory, may be viewed as approximations
      to the second-order CCSD(T-2) model. From numerical comparisons with the CCSD(T
      n) models, we show that the extraordinary performance of the LambdaCCSD[T]/(T)
      and CCSD[T]/(T) models relies on fortuitous, yet rather consistent, cancellations
      of errors. As a side product of our investigations, we are led to reconsider the
      asymmetric LambdaCCSD[T] model due to both its rigorous theoretical foundation
      and its performance, which is shown to be similar to that of the CCSD(T) model
      for systems at equilibrium geometry and superior to it for distorted systems. In
      both the calculations at equilibrium and distorted geometries, however, the
      LambdaCCSD[T] and CCSD(T) models are shown to be outperformed by the fourth-order
      CCSD(T-4) model. 

PMID- 25573549
TI  - Toward accurate thermochemistry of the (24)MgH, (25)MgH, and (26)MgH molecules at
      elevated temperatures: corrections due to unbound states.
AB  - The total partition functions QT and their first two moments Q(')T and Q(")T,
      together with the isobaric heat capacities CpT, are computed a priori for three
      major MgH isotopologues on the temperature range of T = 100-3000 K using the
      recent highly accurate potential energy curve, spin-rotation, and non-adiabatic
      correction functions of Henderson et al. [J. Phys. Chem. A 117, 13373 (2013)].
      Nuclear motion computations are carried out on the ground electronic state to
      determine the (ro)vibrational energy levels and the scattering phase shifts. The
      effect of resonance states is found to be significant above about 1000 K and it
      increases with temperature. Even very short-lived states, due to their relatively
      large number, have significant contributions to QT at elevated temperatures. The
      contribution of scattering states is around one fourth of that of resonance
      states but opposite in sign. Uncertainty estimates are given for the possible
      error sources, suggesting that all computed thermochemical properties have an
      accuracy better than 0.005% up to 1200 K. Between 1200 and 2500 K, the
      uncertainties can rise to around 0.1%, while between 2500 K and 3000 K, a further
      increase to 0.5% might be observed for Q(")T and CpT, principally due to the
      neglect of excited electronic states. The accurate thermochemical data determined
      are presented in the supplementary material for the three isotopologues of
      (24)MgH, (25)MgH, and (26)MgH at 1 K increments. These data, which differ
      significantly from older standard data, should prove useful for astronomical
      models incorporating thermodynamic properties of these species. 

PMID- 25573550
TI  - An analysis of hydrated proton diffusion in ab initio molecular dynamics.
AB  - A detailed understanding of the inherently multiscale proton transport process
      raises a number of scientifically challenging questions. For example, there
      remain many (partially addressed) questions on the molecular mechanism for long
      range proton migration and the potential for the formation of long-lived traps
      giving rise to burst-and-rest proton dynamics. Using results from a sizeable
      collection of ab initio molecular dynamics (AIMD) simulations (totaling ~2.7 ns)
      with various density functional approximations (Becke-Lee-Yang-Parr (BLYP), BLYP
      D3, Hamprecht-Cohen-Tozer-Handy, B3LYP) and temperatures (300-330 K), equilibrium
      and dynamical properties of one excess proton and 128 water molecules are
      studied. Two features in particular (concerted hops and weak hydrogen-bond
      donors) are investigated to identify modes in the system that are strongly
      correlated with the onset of periods of burst-and-rest dynamics. The question of
      concerted hops seeks to identify those time scales over which long-range proton
      transport can be classified as a series of sequential water hopping events or as
      a near-simultaneous concerted process along compressed water wires. The coupling
      of the observed burst-and-rest dynamics with motions of a fourth neighboring
      water molecule (a weak hydrogen-bond donor) solvating the protonated water
      molecule is also investigated. The presence (absence) of hydrogen bonds involving
      this fourth water molecule before and after successful proton hopping events is
      found to be strongly correlated with periods of burst (rest) dynamics (and
      consistent with pre-solvation concepts). By analyzing several realizations of the
      AIMD trajectories on the 100-ps time scale, convergence of statistics can be
      assessed. For instance, it was observed that the probability for a fourth water
      molecule to approach the hydronium, if not already proximal at the beginning of
      the lifetime of the hydronium, is very low, indicative of the formation of stable
      void regions. Furthermore, the correlations of the neighboring water atoms are
      identified as the fourth water approaches the hydronium. Finally, the temperature
      effects on structural and dynamical properties are studied. 

PMID- 25573552
TI  - Generalized method calculating the effective diffusion coefficient in periodic
      channels.
AB  - The method calculating the effective diffusion coefficient in an arbitrary
      periodic two-dimensional channel, presented in our previous paper [P. Kalinay, J.
      Chem. Phys. 141, 144101 (2014)], is generalized to 3D channels of cylindrical
      symmetry, as well as to 2D or 3D channels with particles driven by a constant
      longitudinal external driving force. The next possible extensions are also
      indicated. The former calculation was based on calculus in the complex plane,
      suitable for the stationary diffusion in 2D domains. The method is reformulated
      here using standard tools of functional analysis, enabling the generalization. 

PMID- 25573551
TI  - Extracting the diffusion tensor from molecular dynamics simulation with
      Milestoning.
AB  - We propose an algorithm to extract the diffusion tensor from Molecular Dynamics
      simulations with Milestoning. A Kramers-Moyal expansion of a discrete master
      equation, which is the Markovian limit of the Milestoning theory, determines the
      diffusion tensor. To test the algorithm, we analyze overdamped Langevin
      trajectories and recover a multidimensional Fokker-Planck equation. The recovery
      process determines the flux through a mesh and estimates local kinetic
      parameters. Rate coefficients are converted to the derivatives of the potential
      of mean force and to coordinate dependent diffusion tensor. We illustrate the
      computation on simple models and on an atomically detailed system-the diffusion
      along the backbone torsions of a solvated alanine dipeptide. 

PMID- 25573553
TI  - Accurate vibrational spectra via molecular tailoring approach: a case study of
      water clusters at MP2 level.
AB  - In spite of the recent advents in parallel algorithms and computer hardware, high
      level calculation of vibrational spectra of large molecules is still an uphill
      task. To overcome this, significant effort has been devoted to the development of
      new algorithms based on fragmentation methods. The present work provides the
      details of an efficient and accurate procedure for computing the vibrational
      spectra of large clusters employing molecular tailoring approach (MTA). The
      errors in the Hessian matrix elements and dipole derivatives arising due to the
      approximation nature of MTA are reduced by grafting the corrections from a
      smaller basis set. The algorithm has been tested out for obtaining vibrational
      spectra of neutral and charged water clusters at Moller-Plesset second order
      level of theory, and benchmarking them against the respective full calculation
      (FC) and/or experimental results. For (H2O)16 clusters, the estimated vibrational
      frequencies are found to differ by a maximum of 2 cm(-1) with reference to the
      corresponding FC values. Unlike the FC, the MTA-based calculations including
      grafting procedure can be performed on a limited hardware, yet take a fraction of
      the FC time. The present methodology, thus, opens a possibility of the accurate
      estimation of the vibrational spectra of large molecular systems, which is
      otherwise impossible or formidable. 

PMID- 25573554
TI  - Two-dimensional NMR measurement and point dipole model prediction of paramagnetic
      shift tensors in solids.
AB  - A new two-dimensional Nuclear Magnetic Resonance (NMR) experiment to separate and
      correlate the first-order quadrupolar and chemical/paramagnetic shift
      interactions is described. This experiment, which we call the shifting-d echo
      experiment, allows a more precise determination of tensor principal components
      values and their relative orientation. It is designed using the recently
      introduced symmetry pathway concept. A comparison of the shifting-d experiment
      with earlier proposed methods is presented and experimentally illustrated in the
      case of (2)H (I = 1) paramagnetic shift and quadrupolar tensors of CuCl2?2D2O.
      The benefits of the shifting-d echo experiment over other methods are a factor of
      two improvement in sensitivity and the suppression of major artifacts. From the
      2D lineshape analysis of the shifting-d spectrum, the (2)H quadrupolar coupling
      parameters are <Cq> = 118.1 kHz and <etaq> = 0.88, and the (2)H paramagnetic
      shift tensor anisotropy parameters are <zetaP> = - 152.5 ppm and <etaP> = 0.91.
      The orientation of the quadrupolar coupling principal axis system (PAS) relative
      to the paramagnetic shift anisotropy principal axis system is given by
      (alpha,beta,gamma)=(pi2,pi2,0). Using a simple ligand hopping model, the tensor
      parameters in the absence of exchange are estimated. On the basis of this
      analysis, the instantaneous principal components and orientation of the
      quadrupolar coupling are found to be in excellent agreement with previous
      measurements. A new point dipole model for predicting the paramagnetic shift
      tensor is proposed yielding significantly better agreement than previously used
      models. In the new model, the dipoles are displaced from nuclei at positions
      associated with high electron density in the singly occupied molecular orbital
      predicted from ligand field theory.

PMID- 25573555
TI  - Ultraviolet photodissociation action spectroscopy of the N-pyridinium cation.
AB  - The S1<-S0 electronic transition of the N-pyridinium ion (C5H5NH(+)) is
      investigated using ultraviolet photodissociation (PD) spectroscopy of the bare
      ion and also the N2-tagged complex. Gas-phase N-pyridinium ions photodissociate
      by the loss of molecular hydrogen (H2) in the photon energy range 37,000-45,000
      cm(-1) with structurally diagnostic ion-molecule reactions identifying the 2
      pyridinylium ion as the exclusive co-product. The photodissociation action
      spectra reveal vibronic details that, with the aid of electronic structure
      calculations, support the proposal that dissociation occurs through an
      intramolecular rearrangement on the ground electronic state following internal
      conversion. Quantum chemical calculations are used to analyze the measured
      spectra. Most of the vibronic features are attributed to progressions of totally
      symmetric ring deformation modes and out-of-plane modes active in the
      isomerization of the planar excited state towards the non-planar excited state
      global minimum.

PMID- 25573556
TI  - Planar dicyclic B6S6, B6S6(-), and B6S6(2-) clusters: boron sulfide analogues of
      naphthalene.
AB  - Inorganic analogues of hydrocarbons or polycyclic aromatic hydrocarbons (PAHs)
      are of current interest in chemistry. Based upon global structural searches and
      B3LYP and CCSD(T) calculations, we present herein the perfectly planar dicyclic
      boron sulfide clusters: D2h B6S6 (1, (1)Ag), D2h B6S6(-) (2, (2)B3u), and D2h
      B6S6(2-) (3, (1)Ag). These are the global minima of the systems, being at least
      0.73, 0.81, and 0.53 eV lower in energy, respectively, than their alternative
      isomers at the CCSD(T) level. The D2h structures feature twin B3S2 five-membered
      rings, which are fused together via a B2 unit and terminated by two BS groups.
      Bonding analyses show that the closed-shell B6S6(2-) (3) cluster possesses 10
      delocalized pi electrons, closely analogous to the bonding pattern of the
      aromatic naphthalene C10H8. The B6S6(-) (2) and B6S6 (1) species are readily
      obtained upon removal of one or two pi electrons from B6S6(2-) (3). The results
      build a new analogous relationship between boron sulfide clusters and their PAH
      counterparts. The B6S6(-) (2) monoanion and B6S6(2-) (3) dianion can be
      effectively stabilized in neutral LiB6S6 and Li2B6S6 salts, respectively.

PMID- 25573557
TI  - Pressure effects on the relaxation of an excited nitromethane molecule in an
      argon bath.
AB  - Classical molecular dynamics simulations were performed to study the relaxation
      of nitromethane in an Ar bath (of 1000 atoms) at 300 K and pressures 10, 50, 75,
      100, 125, 150, 300, and 400 atm. The molecule was instantaneously excited by
      statistically distributing 50 kcal/mol among the internal degrees of freedom. At
      each pressure, 1000 trajectories were integrated for 1000 ps, except for 10 atm,
      for which the integration time was 5000 ps. The computed ensemble-averaged
      rotational energy decay is ~100 times faster than the vibrational energy decay.
      Both rotational and vibrational decay curves can be satisfactorily fit with the
      Lendvay-Schatz function, which involves two parameters: one for the initial rate
      and one for the curvature of the decay curve. The decay curves for all pressures
      exhibit positive curvature implying the rate slows as the molecule loses energy.
      The initial rotational relaxation rate is directly proportional to density over
      the interval of simulated densities, but the initial vibrational relaxation rate
      decreases with increasing density relative to the extrapolation of the limiting
      low-pressure proportionality to density. The initial vibrational relaxation rate
      and curvature are fit as functions of density. For the initial vibrational
      relaxation rate, the functional form of the fit arises from a combinatorial model
      for the frequency of nitromethane "simultaneously" colliding with multiple Ar
      atoms. Roll-off of the initial rate from its low-density extrapolation occurs
      because the cross section for collision events with L Ar atoms increases with L
      more slowly than L times the cross section for collision events with one Ar atom.
      The resulting density-dependent functions of the initial rate and curvature
      represent, reasonably well, all the vibrational decay curves except at the lowest
      density for which the functions overestimate the rate of decay. The decay over
      all gas phase densities is predicted by extrapolating the fits to condensed-phase
      densities. 

PMID- 25573558
TI  - Interaction of O(-) and H2 at low temperatures.
AB  - Reactive collisions between O(-) and H2 have been studied experimentally at
      temperatures ranging from 10 K to 300 K using a cryogenic radiofrequency 22-pole
      ion trap. The rate coefficients for associative detachment, leading to H2O + e(
      ), increase with decreasing temperature and reach a flat maximum of 1.8 * 10(-9)
      cm(3) s(-1) at temperatures between 20 K and 80 K. There, the overall reaction
      probability is in good agreement with a capture model indicating efficient non
      adiabatic couplings between the entrance potential energy surfaces. Classical
      trajectory calculations on newly calculated potential energy surfaces as well as
      the topology of the conical intersection seam leading to the neutral surface
      corroborate this. The formation of OH(-) + H via hydrogen transfer, although
      occurring with a probability of a few percent only (about 5 * 10(-11) cm(3) s(-1)
      at temperatures 10-300 K), indicates that there are reaction paths, where
      electron detachment is avoided.

PMID- 25573559
TI  - An experimental and theoretical study of the electronic spectrum of the HBCl free
      radical.
AB  - Following our previous discovery of the spectra of the HBX (X = F, Cl, and Br)
      free radicals [S.-G. He, F. X. Sunahori, and D. J. Clouthier, J. Am. Chem. Soc.
      127, 10814 (2005)], the A(2)A(")Pi-X(2)A(') band systems of the HBCl and DBCl
      free radicals have been studied in detail. The radicals have been prepared in a
      pulsed electric discharge jet using a precursor mixture of BCl3 and H2 or D2 in
      high pressure argon. Laser-induced fluorescence (LIF) and single vibronic level
      emission spectra have been recorded to map out the ground and excited state
      vibrational energy levels. The band system involves a linear-bent transition
      between the two Renner-Teller components of what would be a (2)Pi electronic
      state at linearity. We have used high level ab initio theory to calculate the
      ground and excited state potential energy surfaces and have determined the
      vibronic energy levels variationally. The theory results were used to assign the
      LIF spectra which involve transitions from the ground state zero-point level to
      high vibrational levels of the excited state. The correspondence between theory
      and experiment, including the transition frequencies, upper state band
      symmetries, and H, B, and Cl isotope shifts, was used to validate the
      assignments. 

PMID- 25573560
TI  - Rotationally inelastic scattering of methyl radicals with Ar and N2.
AB  - The rotationally inelastic scattering of methyl radical with Ar and N2 is
      examined at collision energies of 330 +/- 25 cm(-1) and 425 +/- 50 cm(-1),
      respectively. Differential cross sections (DCSs) were measured for different
      final n' rotational levels (up to n' = 5) of the methyl radicals, averaged over
      k' sub-levels, using a crossed molecular beam machine with velocity map imaging.
      For Ar as a collision partner, we present a newly constructed ab initio potential
      energy surface and quantum mechanical scattering calculations of state-resolved
      DCSs. These computed DCSs agree well with the measurements. The DCSs for both Ar
      and N2 collision partners are strongly forward peaked for all spectroscopic lines
      measured. For scattering angles below 60 degrees , the theoretical CD3-Ar DCSs
      show diffraction oscillations that become less pronounced as n' increases, but
      these oscillations are not resolved experimentally. Comparisons are drawn with
      our recently reported DCSs for scattering of methyl radicals with He atoms. 

PMID- 25573561
TI  - Single photon simultaneous K-shell ionization and K-shell excitation. I.
      Theoretical model applied to the interpretation of experimental results on H2O.
AB  - We present in detail a theoretical model that provides absolute cross sections
      for simultaneous core-ionization core-excitation (K(-2)V) and compare its
      predictions with experimental results obtained on the water molecule after
      photoionization by synchrotron radiation. Two resonances of different symmetries
      are assigned in the main K(-2)V peak and comparable contributions from monopolar
      (direct shake-up) and dipolar (conjugate shake-up) core-valence excitations are
      identified. The main peak is observed with a much greater width than the total
      experimental resolution. This broadening is the signature of nuclear dynamics.

PMID- 25573562
TI  - Single photon simultaneous K-shell ionization and K-shell excitation. II.
      Specificities of hollow nitrogen molecular ions.
AB  - The formalism developed in the companion Paper I is used here for the
      interpretation of spectra obtained recently on the nitrogen molecule. Double core
      hole ionization K(-2) and core ionization-core excitation K(-2)V processes have
      been observed by coincidence electron spectroscopy after ionization by
      synchrotron radiation at different photon energies. Theoretical and experimental
      cross sections reported on an absolute scale are in satisfactory agreement. The
      evolution with photon energy of the relative contribution of shake-up and
      conjugate shake-up processes is discussed. The first main resonance in the K(-2)V
      spectrum is assigned to a K(-2)pi(*) state mainly populated by the 1s-> lowest
      unoccupied molecular orbital dipolar excitation, as it is in the K(-1)V NEXAFS
      (Near-Edge X-ray Absorption Fine Structure) signals. Closer to the K(-2)
      threshold Rydberg resonances have been also identified, and among them a K(
      2)sigma(*) resonance characterized by a large amount of 2s/2p hybridization, and
      double K(-2)(2sigma(*)/1pi/3sigma)(-1)1pi(*2) shake-up states. These resonances
      correspond in NEXAFS spectra to, respectively, the well-known sigma(*) shape
      resonance and double excitation K(-1)(2sigma(*)/1pi/3sigma)(-1)1pi(*2)
      resonances, all being positioned above the threshold. 

PMID- 25573563
TI  - Quantum dynamics study on the CHIPR potential energy surface for the hydroperoxyl
      radical: the reactions O + OH?O2 + H.
AB  - Quantum scattering calculations of the O((3)P)+OH((2)Pi)?O2((3)Sigmag (
      ))+H((2)S) reactions are presented using the combined-hyperbolic-inverse-power
      representation potential energy surface [A. J. C. Varandas, J. Chem. Phys. 138,
      134117 (2013)], which employs a realistic, ab initio-based, description of both
      the valence and long-range interactions. The calculations have been performed
      with the ABC time-independent quantum reactive scattering computer program based
      on hyperspherical coordinates. The reactivity of both arrangements has been
      investigated, with particular attention paid to the effects of vibrational
      excitation. By using the J-shifting approximation, rate constants are also
      reported for both the title reactions. 

PMID- 25573564
TI  - Vibrational predissociation and vibrationally induced isomerization of 3
      aminophenol-ammonia.
AB  - We investigate the vibrational predissociation dynamics of the hydrogen-bonded 3
      aminophenol-ammonia cluster (3-AP-NH3) in the OH and NH stretching regions.
      Vibrational excitation provides enough energy to dissociate the cluster into its
      constituent 3-AP and NH3 monomers, and we detect the 3-AP fragments via (1 + 1)
      resonance-enhanced multiphoton ionization (REMPI). The distribution of
      vibrational states of the 3-AP fragment suggests the presence of two distinct
      dissociation pathways. The first dissociation channel produces a broad,
      unstructured feature in the REMPI-action spectrum after excitation of any of the
      OH or NH stretching vibrations, pointing to a nearly statistical dissociation
      pathway with extensive coupling among the vibrations in the cluster during the
      vibrational predissociation. The second dissociation channel produces distinct,
      resolved features on top of the broad feature but only following excitation of
      the OH or symmetric NH3 stretch in the cluster. This striking mode-specificity is
      consistent with strong coupling of these two modes to the dissociation coordinate
      (the O-H?N bond). The presence of clearly resolved transitions to the electronic
      origin and to the 10a(2) + 10b(2) state of the cis-3-AP isomer shows that
      vibrational excitation is driving the isomerization of the trans-3-AP-NH3 isomer
      to the cis-3-AP-NH3 isomer in the course of the dissociation. 

PMID- 25573565
TI  - Helium induced fine structure in the electronic spectra of anthracene derivatives
      doped into superfluid helium nanodroplets.
AB  - Electronic spectra of organic molecules doped into superfluid helium nanodroplets
      show characteristic features induced by the helium environment. Besides a solvent
      induced shift of the electronic transition frequency, in many cases, a spectral
      fine structure can be resolved for electronic and vibronic transitions which goes
      beyond the expected feature of a zero phonon line accompanied by a phonon wing as
      known from matrix isolation spectroscopy. The spectral shape of the zero phonon
      line and the helium induced phonon wing depends strongly on the dopant species.
      Phonon wings, for example, are reported ranging from single or multiple sharp
      transitions to broad (Deltanu > 100 cm(-1)) diffuse signals. Despite the large
      number of example spectra in the literature, a quantitative understanding of the
      helium induced fine structure of the zero phonon line and the phonon wing is
      missing. Our approach is a systematic investigation of related molecular
      compounds, which may help to shed light on this key feature of microsolvation in
      superfluid helium droplets. This paper is part of a comparative study of the
      helium induced fine structure observed in electronic spectra of anthracene
      derivatives with particular emphasis on a spectrally sharp multiplet splitting at
      the electronic origin. In addition to previously discussed species, 9
      cyanoanthracene and 9-chloroanthracene will be presented in this study for the
      first time. 

PMID- 25573566
TI  - Dopant effects on 2-ethyl-1-hexanol: a dual-channel impedance spectroscopy and
      neutron scattering study.
AB  - A two-channel impedance technique has been used to study the relaxation behavior
      of 2-ethyl-1-hexanol with polar and non-polar dopants at the few percent
      concentration level over a wide temperature and frequency range. The non-polar
      dopants shift both the Debye and the primary structural relaxation time in the
      same direction, to shorter times for 3-methylpentane and to longer times for
      squalane, consistent with the relative glass transition temperatures (Tg) of the
      components. By contrast, polar dopants such as water or methanol modify the alpha
      process towards slower dynamics and increased amplitude, while the Debye process
      is accelerated and with a decreased amplitude. This effect of adding water to
      alcohol is explained by water promoting more compact structures with reduced
      Kirkwood correlation factors. This picture is consistent with a shift in the
      neutron scattering pre-peak to lower scattering vectors and with simulation work
      on alcohol-water systems. 

PMID- 25573567
TI  - Conformation and interactions of dopamine hydrochloride in solution.
AB  - The aqueous solution of dopamine hydrochloride has been investigated using
      neutron and X-ray total scattering data together with Monte-Carlo based modelling
      using Empirical Potential Structure Refinement. The conformation of the
      protonated dopamine molecule is presented and the results compared to the
      conformations found in crystal structures, dopamine-complexed protein crystal
      structures and predicted from theoretical calculations and pharmacophoric models.
      It is found that protonated dopamine adopts a range of conformations in solution,
      highlighting the low rotational energy barrier between different conformations,
      with the preferred conformation being trans-perpendicular. The interactions
      between each of the species present (protonated dopamine molecules, water
      molecules, and chloride anions) have been determined and are discussed with
      reference to interactions observed in similar systems both in the liquid and
      crystalline state, and predicted from theoretical calculations. The expected
      strong hydrogen bonds between the strong hydrogen bond donors and acceptors are
      observed, together with evidence of weaker CH hydrogen bonds and pi interactions
      also playing a significant role in determining the arrangement of adjacent
      molecules. 

PMID- 25573568
TI  - Study of the thermodynamic properties of CeO2 from ab initio calculations: the
      effect of phonon-phonon interaction.
AB  - The thermodynamic properties of CeO2 have been reevaluated by a simple but
      accurate scheme. All our calculations are based on the self-consistent ab initio
      lattice dynamical (SCAILD) method that goes beyond the quasiharmonic
      approximation. Through this method, the effects of phonon-phonon interactions are
      included. The obtained thermodynamic properties and phonon dispersion relations
      are in good agreement with experimental data when considering the correction of
      phonon-phonon interaction. We find that the correction of phonon-phonon
      interaction is equally important and should not be neglected. At last, by
      comparing with quasiharmonic approximation, the present scheme based on SCAILD
      method is probably more suitable for high temperature systems. 

PMID- 25573569
TI  - Sensing polarization effects through the analysis of the effective C6 dispersion
      coefficients in NaCl solutions.
AB  - Density functional theory based ab initio molecular dynamics is used to obtain
      microscopic details of the interactions in sodium chloride solutions. By
      following the changes in the atomic C6 coefficients under the Tkatchenko
      Scheffler's scheme, we were able to identify two different coordination
      situations for the Cl(-) ion with significant different capabilities to perform
      dispersion interactions. This capability is enhanced when the ion-ion distance
      corresponds to the contact ion-pair situation. Also, the oxygen and hydrogen
      atoms of the water molecules change their aptitudes to interact through van der
      Waals like terms when they are close to the cation region of the ion-pair. These
      results have interesting implications on the design of force fields to model
      electrolyte solutions. 

PMID- 25573570
TI  - In silico infrared and Raman spectroscopy under pressure: the case of CaSnO3
      perovskite.
AB  - The CaSnO3 perovskite is investigated under geochemical pressure, up to 25 GPa,
      by means of periodic ab initio calculations performed at B3LYP level with local
      Gaussian-type orbital basis sets. Structural, elastic, and spectroscopic (phonon
      wave-numbers, infrared and Raman intensities) properties are fully characterized
      and discussed. The evolution of the Raman spectrum of CaSnO3 under pressure is
      reported to remarkably agree with a recent experimental determination [J. Kung,
      Y. J. Lin, and C. M. Lin, J. Chem. Phys. 135, 224507 (2011)] as regards both wave
      number shifts and intensity changes. All phonon modes are symmetry-labeled and
      bands assigned. The single-crystal total spectrum is symmetry-decomposed into the
      six directional spectra related to the components of the polarizability tensor.
      The infrared spectrum at increasing pressure is reported for the first time and
      its main features discussed. All calculations are performed using the Crystal14
      program, taking advantage of the new implementation of analytical infrared and
      Raman intensities for crystalline materials. 

PMID- 25573571
TI  - A structural study of a two-dimensional electrolyte by Monte Carlo simulations.
AB  - Properties of superconducting and superfluid thin films, modeled as a two
      dimensional classic Coulomb fluid, are connected to the molecular structure of
      the system. Monte Carlo simulations to explore structural properties and ordering
      in the classical two-dimensional Coulomb fluid were performed. The density
      dependence of translational order parameters at various temperatures and cluster
      distribution below and above the Kosterlitz-Thouless line were studied, and the
      percolation temperature threshold was determined. Results show that one could
      detect the insulator-conductor transition by observing the translational order
      parameters, average cluster number, or mean cluster size besides dielectric
      constant and dipole moment of the system. 

PMID- 25573572
TI  - Molecular simulation of translational and rotational diffusion of Janus
      nanoparticles at liquid interfaces.
AB  - We perform molecular dynamics simulations to understand the translational and
      rotational diffusion of Janus nanoparticles at the interface between two
      immiscible fluids. Considering spherical particles with different affinity to
      fluid phases, both their dynamics as well as the fluid structure around them are
      evaluated as a function of particle size, amphiphilicity, fluid density, and
      interfacial tension. We show that as the particle amphiphilicity increases due to
      enhanced wetting of each side with its favorite fluid, the rotational thermal
      motion decreases. Moreover, the in-plane diffusion of nanoparticles at the
      interface becomes slower for more amphiphilic particles, mainly due to the
      formation of a denser adsorption layer. The particles induce an ordered structure
      in the surrounding fluid that becomes more pronounced for highly amphiphilic
      nanoparticles, leading to increased resistance against nanoparticle motion. A
      similar phenomenon is observed for homogeneous particles diffusing in bulk upon
      increasing their wettability. Our findings can provide fundamental insight into
      the dynamics of drugs and protein molecules with anisotropic surface properties
      at biological interfaces including cell membranes. 

PMID- 25573573
TI  - Demixing and confinement of non-additive hard-sphere mixtures in slit pores.
AB  - Using Monte Carlo simulation, we study the influence of geometric confinement on
      demixing for a series of symmetric non-additive hard spheres mixtures confined in
      slit pores. We consider both a wide range of positive non-additivities and a
      series of pore widths, ranging from the pure two dimensional limit to a large
      pore width where results are close to the bulk three dimensional case. Critical
      parameters are extracted by means of finite size analysis. As a general trend, we
      find that for this particular case in which demixing is induced by volume
      effects, the critical demixing densities (and pressures) increase due to
      confinement between neutral walls, following the expected behavior for phase
      equilibria of systems confined by pure repulsive walls: i.e., confinement
      generally enhances miscibility. However, a non-monotonous dependence of the
      critical pressure and density with pore size is found for small non-additivities.
      In this latter case, it turns out that an otherwise stable bulk mixture can be
      unexpectedly forced to demix by simple geometric confinement when the pore width
      decreases down to approximately one and a half molecular diameters. 

PMID- 25573574
TI  - Investigation of the deposition and thermal behavior of striped phases of
      unsymmetric disulfide self-assembled monolayers on Au(111): the case of 11
      hydroxyundecyl decyl disulfide.
AB  - Self-assembled monolayers (SAMs) of unsymmetric disulfides on Au(111) are used to
      form mixed SAMs that can be utilized in many applications. Here, we have studied
      11-hydroxyundecyl decyl disulfide (CH3-(CH2)9-S-S-(CH2)11-OH, HDD) SAMs produced
      by supersonic molecular beam deposition and characterized by He diffraction. The
      film growth was monitored at different temperatures up to a coverage which
      corresponds to a full lying down phase and the diffraction analysis shows that
      below 250 K the phase is different from the phase measured above 300 K. During
      the annealing of the film, two phase transitions were observed, at 250 K and 350
      K. The overall data suggest that the former is related to an irreversible phase
      separation of HDD above 250 K to decanethiolate (-S-(CH2)9-CH3, DTT) and
      hydroxyundecylthiolate (-S-(CH2)11-OH, MUDT), while the latter to a reversible
      melting of the film. Above 450 K, the specular intensity shows an increase
      related to film desorption and different chemisorbed states were observed with
      energies in the same range as observed for decanethiol (H-S-(CH2)9-CH3, DT) and
      mercaptoundecanol (H-S-(CH2)11-OH, MUD) SAMs. 

PMID- 25573575
TI  - Modeling selective intergranular oxidation of binary alloys.
AB  - Intergranular attack of alloys under hydrothermal conditions is a complex problem
      that depends on metal and oxygen transport kinetics via solid-state and channel
      like pathways to an advancing oxidation front. Experiments reveal very different
      rates of intergranular attack and minor element depletion distances ahead of the
      oxidation front for nickel-based binary alloys depending on the minor element.
      For example, a significant Cr depletion up to 9 MUm ahead of grain boundary crack
      tips was documented for Ni-5Cr binary alloy, in contrast to relatively moderate
      Al depletion for Ni-5Al (~100 s of nm). We present a mathematical kinetics model
      that adapts Wagner's model for thick film growth to intergranular attack of
      binary alloys. The transport coefficients of elements O, Ni, Cr, and Al in bulk
      alloys and along grain boundaries were estimated from the literature. For planar
      surface oxidation, a critical concentration of the minor element can be
      determined from the model where the oxide of minor element becomes dominant over
      the major element. This generic model for simple grain boundary oxidation can
      predict oxidation penetration velocities and minor element depletion distances
      ahead of the advancing front that are comparable to experimental data. The
      significant distance of depletion of Cr in Ni-5Cr in contrast to the localized Al
      depletion in Ni-5Al can be explained by the model due to the combination of the
      relatively faster diffusion of Cr along the grain boundary and slower diffusion
      in bulk grains, relative to Al. 

PMID- 25573576
TI  - Contact theorems for anisotropic fluids near a hard wall.
AB  - In this paper, from the Born-Green-Yvon equation, we formulate a general
      expression for the contact value of the singlet distribution function for
      anisotropic fluids near a hard wall. This expression consists of two separate
      contributions. One is related to the bulk partial pressure for a given
      orientation of the molecules. The second is related to the anchoring phenomena
      and is characterized by the direct interaction between the molecules and the
      wall. Given this relation, we formulate the contact theorems for the density and
      order parameter profiles. The results are illustrated by the case of a nematic
      fluid near a hard wall. 

PMID- 25573577
TI  - Probing the molecular connectivity of water confined in polymer hydrogels.
AB  - The molecular connectivity and the extent of hydrogen-bond patterns of water
      molecules confined in the polymer hydrogels, namely, cyclodextrin nanosponge
      hydrogels, are here investigated by using vibrational spectroscopy experiments.
      The proposed spectroscopic method exploits the combined analysis of the
      vibrational spectra of polymers hydrated with water and deuterated water, which
      allows us to separate and selectively investigate the temperature-evolution of
      the HOH bending mode of engaged water molecules and of the vibrational modes
      assigned to specific chemical groups of the polymer matrix involved in the
      physical interactions with water. As main results, we find a strong experimental
      evidence of a liquid-like behaviour of water molecules confined in the nano
      cavities of hydrogel and we observe a characteristic destructuring effect on the
      hydrogen-bonds network of confined water induced by thermal motion. More
      interestingly, the extent of this temperature-disruptive effect is found to be
      selectively triggered by the cross-linking degree of the hydrogel matrix. These
      results give a more clear picture of the molecular mechanism of water confinement
      in the pores of nanosponge hydrogel and open the possibility to exploit the
      spectroscopic method here proposed as investigating tools for water-retaining
      soft materials. 

PMID- 25573578
TI  - Virial coefficients and demixing in the Asakura-Oosawa model.
AB  - The problem of demixing in the Asakura-Oosawa colloid-polymer model is
      considered. The critical constants are computed using truncated virial expansions
      up to fifth order. While the exact analytical results for the second and third
      virial coefficients are known for any size ratio, analytical results for the
      fourth virial coefficient are provided here, and fifth virial coefficients are
      obtained numerically for particular size ratios using standard Monte Carlo
      techniques. We have computed the critical constants by successively considering
      the truncated virial series up to the second, third, fourth, and fifth virial
      coefficients. The results for the critical colloid and (reservoir) polymer
      packing fractions are compared with those that follow from available Monte Carlo
      simulations in the grand canonical ensemble. Limitations and perspectives of this
      approach are pointed out. 

PMID- 25573579
TI  - Bistability in a self-assembling system confined by elastic walls: exact results
      in a one-dimensional lattice model.
AB  - The impact of confinement on self-assembly of particles interacting with short
      range attraction and long-range repulsion potential is studied for thermodynamic
      states corresponding to local ordering of clusters or layers in the bulk. Exact
      and asymptotic expressions for the local density and for the effective potential
      between the confining surfaces are obtained for a one-dimensional lattice model
      introduced by J. Pekalski et al. [J. Chem. Phys. 138, 144903 (2013)]. The simple
      asymptotic formulas are shown to be in good quantitative agreement with exact
      results for slits containing at least 5 layers. We observe that the
      incommensurability of the system size and the average distance between the
      clusters or layers in the bulk leads to structural deformations that are
      different for different values of the chemical potential MU. The change of the
      type of defects is reflected in the dependence of density on MU that has a shape
      characteristic for phase transitions. Our results may help to avoid
      misinterpretation of the change of the type of defects as a phase transition in
      simulations of inhomogeneous systems. Finally, we show that a system confined by
      soft elastic walls may exhibit bistability such that two system sizes that differ
      approximately by the average distance between the clusters or layers are almost
      equally probable. This may happen when the equilibrium separation between the
      soft boundaries of an empty slit corresponds to the largest stress in the
      confined self-assembling system. 

PMID- 25573580
TI  - Hydrodynamic interactions between a sphere and a number of small particles.
AB  - Exact expressions are derived for the pair and three-body hydrodynamic
      interactions between a sphere and a number of small particles immersed in a
      viscous incompressible fluid. The analysis is based on the Stokes equations of
      low Reynolds number hydrodynamics. The results follow by a combination of the
      solutions for flow about a sphere with no-slip boundary condition derived by
      Stokes and Kirchhoff and the result derived by Oseen for the Green tensor of
      Stokes equations in the presence of a fixed sphere. 

PMID- 25573581
TI  - The meaning of the "universal" WLF parameters of glass-forming polymer liquids.
AB  - Although the Williams-Landell-Ferry (WLF) equation for the segmental relaxation
      time tau(T) of glass-forming materials is one of the most commonly encountered
      relations in polymer physics, its molecular basis is not well understood. The WLF
      equation is often claimed to be equivalent to the Vogel-Fulcher-Tammann (VFT)
      equation, even though the WLF expression for tau(T) contains no explicit
      dependence on the fragility parameter D of the VFT equation, while the VFT
      equation lacks any explicit reference to the glass transition temperature Tg, the
      traditionally chosen reference temperature in the WLF equation. The observed
      approximate universality of the WLF parameters C1((g)) and C2((g)) implies that
      tau(T) depends only on T-Tg, a conclusion that seems difficult to reconcile with
      the VFT equation where the fragility parameter D largely governs the magnitude of
      tau(T). The current paper addresses these apparent inconsistencies by first
      evaluating the macroscopic WLF parameters C1((g)) and C2((g)) from the
      generalized entropy theory of glass-formation and then by determining the
      dependence of C1((g)) and C2((g)) on the microscopic molecular parameters
      (including the strength of the cohesive molecular interactions and the degree of
      chain stiffness) and on the molar mass of the polymer. Attention in these
      calculations is restricted to the temperature range (Tg < T < Tg + 100 K), where
      both the WLF and VFT equations apply.

PMID- 25573582
TI  - Chain end mobilities in polymer melts--a computational study.
AB  - The Rouse model can be regarded as the standard model to describe the dynamics of
      a short polymer chain under melt conditions. In this contribution, we explicitly
      check one of the fundamental assumptions of this model, namely, that of a uniform
      friction coefficient for all monomers, on the basis of MD simulation data of a
      poly(ethylene oxide) (PEO) melt. This question immediately arises from the fact
      that in a real polymer melt, the terminal monomers have on average more
      intermolecular neighbors than the central monomers, and one would expect that
      exactly these details affect the precise value of the friction coefficient. The
      mobilities are determined by our recently developed statistical method, which
      provides detailed insights into the local polymer dynamics. Moreover, it yields
      complementary information to that obtained from the mean square displacement
      (MSD) or the Rouse mode analysis. It turns out that the Rouse assumption of a
      uniform mobility is fulfilled to a good approximation for the PEO melt. However,
      a more detailed analysis reveals that the underlying microscopic dynamics are
      highly affected by different contributions from intra- and intermolecular
      excluded volume interactions, which cannot be taken into account by a modified
      friction coefficient. Minor deviations occur only for the terminal monomers on
      larger time scales, which can be attributed to the presence of two different
      escape mechanisms from their first coordination sphere. These effects remain
      elusive when studying the dynamics with the MSD only. 

PMID- 25573583
TI  - Effect of temperature on the low-frequency vibrational spectrum and relative
      structuring of hydration water around a single-stranded DNA.
AB  - Molecular dynamics simulations of the single-stranded DNA oligomer (5'-CGCGAAT
      TCGCG-3') in aqueous solution have been carried out at different temperatures
      between 160 K and 300 K. The effects of temperature on the low-frequency
      vibrational spectrum and local structural arrangements of water molecules
      hydrating the DNA strand have been explored in detail. The low-frequency density
      of states distributions reveal that increasingly trapped transverse water motions
      play a dominant role in controlling the band corresponding to O?O?O bending or
      transverse oscillations of hydration water at supercooled temperatures. In
      addition, presence of a broad band around 260 (+/-20) cm(-1) under supercooled
      conditions indicates transformation from high density liquid-like structuring of
      hydration water at higher temperatures to that of a low density liquid at lower
      temperatures. It is found that long-range correlations between the supercooled
      hydration water molecules arise due to such local structural transition around
      the DNA oligomer. 

PMID- 25573584
TI  - The effects of multiple probes on the hybridization of target DNA on surfaces.
AB  - DNA microarrays have disruptive potential in many fields including genetics and
      medicine, but the technology has yet to find widespread clinical use due to poor
      reliability. Microarrays work on the principle of hybridization and can only be
      as dependable as this process is reliable. As such, a significant amount of
      theoretical research has been done to understand hybridization on surfaces on the
      molecular level. Previous simulations of a target strand with a single, surface
      tethered probe molecule have yielded valuable insights, but such is an ideal
      system and little is known about the effects of multiple probes-a situation that
      more closely approximates the real system. This work uses molecular simulation to
      determine the specific differences in duplex stability between one, three, six,
      and nine tethered probes on a surface. The results show that it is more difficult
      for a single target to hybridize to a probe as the number of probes on the
      surface increases due to crowding effects; however, once hybridized, the duplex
      is more stable than when fewer probes are present. The data also indicate that
      hybridization of a target to a probe on the face of a group of probes is more
      stable than hybridization to probes at the edge or center locations. Taken as a
      whole, the results offer new insights into the cause of the poor reproducibility
      exhibited by microarrays. 

PMID- 25573585
TI  - Kinetic regulation mechanism of pbuE riboswitch.
AB  - Riboswitches are RNA residue segments located in untranslated regions of
      messenger RNAs. These folded segments directly bind ligands through shape
      complementarity and specific interactions in cells and alter the expression of
      genes at the transcriptional or translational level through conformation change.
      Using the recently developed systematic helix-based computational method to
      predict the cotranscription folding kinetics, we theoretically studied the
      cotranscription folding behavior of the Bacillus subtilis pbuE riboswitch in the
      absence and presence of the ligand. The ligand concentration, the transcription
      speed, and the transcription pausing are incorporated into the method. The
      results are in good agreement with the experimental results. We find that there
      are no obvious misfolded structures formed during the transcription and the
      formation of the ligand bound state is rate-limited by the association of the
      ligand and the RNA. For this kinetically driven riboswitch, the ligand
      concentration, the transcription speed, and the transcription pausing are coupled
      to perform regulatory activity. 

PMID- 25573586
TI  - Erratum: "Third and fourth virial coefficients for hard disks in narrow channels"
      [J. Chem. Phys. 140, 244504 (2014)].

PMID- 25573587
TI  - Simultaneous detection and quantification of indole-3-acetic acid (IAA) and
      indole-3-butyric acid (IBA) produced by rhizobacteria from l-tryptophan (Trp)
      using HPTLC.
AB  - A simple, quick and reliable method is proposed for the detection and
      quantitation of indole-3-acetate (IAA) and indole-3-butyrate (IBA), an auxin
      phytohormone produced by rhizobacteria from l-tryptophan (Trp) metabolism using
      high performance thin-layer chromatography (HPTLC). Microbial auxin biosynthesis
      routes involve Trp as a precursor where other than IAA and IBA, products such as
      indole-3-pyruvate (IPA), indole-3-acetamide (IAM), tryptamine, indole-3
      acetonitrile (IAN), indole-3-lactic acid (ILA) and indole-3-acetaldehyde (IAAld)
      are also produced. In traditional spectrophotometric method, Salkowski reagent
      develops color by reacting with indolic compounds. The color development is non
      specific contributed by several Trp derivatives produced by rhizobacteria rather
      than IAA only. To overcome this limitation, HPTLC based protocol is developed to
      precisely detect and quantify IAA and IBA in the range of 100 to 1000ng per spot.
      This protocol is applicable to detect and quantify IAA and IBA from microbial
      samples ignoring other Trp derivatives. For microbial samples, the
      spectrophotometric method gives larger values as compared to HPTLC derived values
      which may be attributed by total indolic compounds reacting with Salkowski
      reagent rather than only IAA and/or IBA. 

PMID- 25573588
TI  - HPTLC analysis of Scoparia dulcis Linn (Scrophulariaceae) and its larvicidal
      potential against dengue vector Aedes aegypti.
AB  - This study evaluates the larvicidal activity of Scoparia dulcis aqueous extract
      against dengue vector and determines its major chemical components. The extract
      was tested at various concentrations ranging from 0.1 to 2 mg/mL against Aedes
      aegypti larvae. The extracts displayed significant larvicidal efficacy against
      Ae. aegypt species after 24 h exposure revealing LC50 of 3.3835 (mg/mL) and LC90
      of 5.7578 (mg/mL). Finger printing profile carried out by CAMAG automatic TLC
      sample applicator programmed through WIN CATS software revealed peaks with
      different Rf values for three different volumes injected: 16, 15 and 18 peaks
      were spotted for 3, 6 and 9 MUL, respectively. Ascending order of Rf values was
      also ascertained for each peak recorded. This study clearly signifies that S.
      dulcis extract contains numerous compounds that are known to have larvicidal
      properties which clearly substantiates its efficacy on Ae. aegypti larvae.

PMID- 25573590
TI  - A critical analysis of the relationship between aldehyde dehydrogenases-2
      Glu487Lys polymorphism and colorectal cancer susceptibility.
AB  - Studies investigating the association between genetic polymorphism of aldehyde
      dehydrogenases-2 (ALDH-2) Glu487Lys and colorectal cancer (CRC) risk have
      reported conflicting results. Given this uncertainty, we carried out a critical
      analysis of published case-control studies to derive a more precise estimation of
      this relationship. Published literature from PubMed, EMBASE and China Knowledge
      Resource Integrated Database were retrieved, and the literature search was
      updated in June 2014. Eleven studies comprising 6965 subjects were selected (2300
      cases and 4665 controls). Overall, our study showed no statistical significance
      for CRC risk associated with any of the genetic models of ALDH-2 Glu487Lys
      polymorphism. When studies were stratified for control source, a decreased risk
      of CRC for participants with Lys/Lys was observed in population based case
      control studies [Lys/Lys vs. (Glu/Lys + Glu/Glu): odds ratio (OR) = 0.57, 95%
      confidence interval (CI) = 0.38-0.87]. Furthermore, we also confirmed the
      significant correlation between Glu487Lys polymorphism and the influence on the
      risk of rectal cancer in males [Glu/Glu vs. (Glu/Lys + Lys/Lys): OR = 1.52, 95%CI
      = 1.10-2.08]. The combined effects of the two gene polymorphisms [ALDH-2 and
      alcohol dehydrogenase 1B (ADH-1B)] were also studied. Compared with subjects
      having ALDH-2 Lys+ with ADH-1B His/His, ORs and 95%CIs for those with ALDH-2
      Glu/Glu and ADH-1B His/His was 3.42(0.57-20.38). Similar trends were observed for
      the other two types of comparisons. Our study supports that ALDH-2 Glu487Lys
      polymorphism is associated with significant reduced risks of CRC in population
      based samples, and of rectal cancer in males.

PMID- 25573589
TI  - Frameshift mutations of MUC15 gene in gastric and its regional heterogeneity in
      gastric and colorectal cancers.
AB  - Mucins are important in tumorigenesis and expressional alterations of mucins are
      common in human cancers. A membrane-bound mucin MUC15 and secreted mucins MUC4
      and MUC7 are known to involve in tumorigenesis, but their mutation status in
      cancers remains unknown. Aim of this study was to explore whether MUC4, MUC7 and
      MUC15 genes are mutated and expressionally altered in gastric (GC) and colorectal
      cancers (CRC). In a public database, we found that MUC15 and MUC7 genes had
      mononucleotide repeats in the coding sequences that might be mutation targets in
      the cancers with microsatellite instability (MSI). We analyzed the mutations in
      90 GC and 141 CRC (high MSI (MSI-H) or stable MSI/low MSI (MSS/MSI-L)) by single
      strand conformation polymorphism analysis and DNA sequencing. In the present
      study, we found MUC15 frameshift mutations (14.7% of GC and 15.2% of CRC with MSI
      H), MUC 7 frameshift mutations (2.9% of GC with MSI-H) and MUC4 frameshift
      mutations (8.8% of GC and 3.8% of CRC with MSI-H). These mutations were not found
      in in MSS/MSI-L (0/118). Additionally, we analyzed intratumoral heterogeneity
      (ITH) of MUC15 mutation in 16 CRC and found that seven CRC (43.8%) harbored
      regional ITH of MUC15. We also analyzed MUC15 expression in GC and CRC by
      immunohistochemistry. Negative MUC15 expression was identified in 15-41% of the
      GC and CRC irrespective of MSI status. Of note, the negative expression was more
      common in those with MUC15 mutations. We identified alterations of MUC genes at
      various levels (frameshift mutations, genetic ITH and expression loss), which
      together might play a role in tumorigenesis of GC and CRC with MSI-H. Our data
      suggest that mutation analysis in multiple regions is needed for a better
      evaluation of mutation status in CRC with MSI-H.

PMID- 25573591
TI  - Non-malignant breast papillary lesions - b3 diagnosed on ultrasound--guided 14
      gauge needle core biopsy: analysis of 114 cases from a single institution and
      review of the literature.
AB  - One-hundred-fourteen consecutive cases of breast ultrasound-guided 14-gauge
      needle core biopsy (14G NCB) performed from January 2001 to June 2013 and
      diagnosed as non-malignant papillary lesion (PL)-B3, were reviewed and compared
      with definitive histological diagnosis on surgical excision (SE) to evaluate the
      diagnostic accuracy of ultrasound-guided 14G NCB. PL with epithelial atypia on
      14G NCB were associated to malignancy on definitive histological diagnosis on SE
      in 22 (7 DCIS and 15 invasive carcinomas) of 46 cases with an underestimation
      rate of 47.8 %, while 9 (4 DCIS and 5 invasive carcinomas) cases out of 68 cases
      of PL without epithelial atypia were upgraded to carcinoma with an
      underestimation rate of 13.2 %. In cases of PL with epithelial atypia on
      ultrasound-guided 14G NCB, SE appears mandatory due to the high risk of
      associated malignancy. The diagnosis of PL without epithelial atypia on
      ultrasound-guided 14G NCB does not exclude malignancy at subsequent SE,
      consequently further assessment (by surgical or vacuum-assisted excision) is
      recommended to avoid the risk of delaying a diagnosis of malignancy, although
      this tends to be lower (1 in 8 patients). 

PMID- 25573592
TI  - Functional variants of lipid level modifier MLXIPL, GCKR, GALNT2, CILP2, ANGPTL3
      and TRIB1 genes in healthy Roma and Hungarian populations.
AB  - The role of triglyceride metabolism in different diseases, such as cardiovascular
      or cerebrovascular diseases is still under extensive investigations. In genome
      wide studies several polymorphisms have been reported, which are highly
      associated with plasma lipid level changes. Our goal was to examine eight
      variants: rs12130333 at the ANGPTL3, rs16996148 at the CILP2, rs17321515 at the
      TRIB1, rs17145738 and rs3812316 of the MLXIPL, rs4846914 at GALNT2, rs1260326 and
      rs780094 residing at the GCKR loci. A total of 399 Roma (Gypsy) and 404 Hungarian
      population samples were genotyped using PCR-RFLP method. Significant differences
      were found between Roma and Hungarian population samples in both MLXIPL variants
      (C allele frequency of rs17145738: 94.1% vs. 85.6%, C allele frequency of
      rs3812316: 94.2% vs. 86.8% in Romas vs. in Hungarians, p < 0.05), in ANGPTL3 (T
      allele frequency of rs1213033: 12.2% vs. 18.5% in Romas vs. Hungarians, p < 0.05)
      and GALNT2 (G allele frequency of rs4846914: 46.6% vs. 54.5% Romas vs. in
      Hungarians, p < 0.05), while no differences over SNPs could be verified and the
      known minor alleles showed no correlation with triglyceride levels in any
      population samples. The current study revealed fundamental differences of known
      triglyceride modifying SNPs in Roma population. Failure of finding evidence for
      affected triglyceride metabolism shows that these susceptibility genes are much
      less effective compared for example to the apolipoprotein A5 gene.

PMID- 25573593
TI  - JAK2 V617F, MPL, and CALR mutations in essential thrombocythaemia and major
      thrombotic complications: a single-institute retrospective analysis.
AB  - Thrombo-haemorrhagic events are the main cause of morbidity and mortality in
      essential thrombocythemia. The aim of this study was to estimate the incidence of
      thrombotic events and the impact of the JAK2V617F, MPL (W515L, W515K, W515R,
      W515A and S505N) and CALR (type-1, type-2) mutations on 101 essential
      thrombocythaemia patients (72 females and 29 males with a mean age of 61 years)
      diagnosed in a Southern Hungarian regional academic centre. The incidence of
      major thrombosis was 13.86 %. Sixty percent of the patients carried the JAK2V617F
      mutation. The MPL mutations were analysed by sequencing and the W515L was the
      only one we could identify with an incidence of 3.96 %. Type-2 CALR mutation
      could be identified in 3 cases among the patients who had JAK2/MPL-unmutated ET.
      Statistical analyses revealed that the JAK2V617F mutation was associated with
      significantly increased levels of platelet (p = 0.042), haemoglobin (p = 0.000),
      red blood cell (p = 0.000) and haematocrit (p = 0.000) and hepatomegaly (p =
      0.045) at diagnosis compared to JAK2V617F negative counterparts, however there
      was no significant association between the JAK2V617F mutation status (relative
      risk: 1.297, 95 % CI 0.395-4.258; p = 0.668) and subsequent thrombotic
      complications. The impact of JAK2V617F, MPL W515L and CALR mutations on the
      clinical findings at the diagnosis of ET was obvious, but their statistically
      significant role in the prediction of thrombotic events could not be proven in
      this study. Our results indirectly support the concept that, besides the
      quantitative and qualitative changes in the platelets, the mechanisms leading to
      thrombosis are more complex and multifactorial.

PMID- 25573594
TI  - FOXC2 expression is associated with tumor proliferation and invasion potential in
      oral tongue squamous cell carcinoma.
AB  - Forkhead box protein C2 (FOXC2) is a gene encoding a transcription factor that
      controls the generation of mesodermal tissue including vascular and lymphatic
      tissues. FOXC2 has previously been associated with EMT and tumor angiogenesis in
      various cancers. Moreover, a relationship between the expression of FOXC2 and
      poor prognosis has been reported in various cancers. We herein examined the
      clinicopathological significance of FOXC2 in oral tongue squamous cell carcinoma
      (OTSCC) and attempted to clarify the function of FOXC2 in OTSCC cell lines in
      vitro. The overexpression of FOXC2 was more frequent in cancers with higher
      grades according to the pattern of invasion (grade 4 vs. 1-3; p < 0.05). A
      correlation was observed between the expression of FOXC2 and that of VEGF-A and 
      C (VEGF-A; p < 0.05, VEGF-C; p < 0.001). The high-FOXC2 expression group had a
      significantly poorer prognosis than that of the low-expression group (p < 0.001).
      Multivariate analysis indicated that the overexpression of FOXC2 may also be an
      independent prognostic factor, similar to N classification (N0 vs 1/2; p < 0.05),
      stage classification (stage I/II vs III/IV; p < 0.05), pattern of invasion (grade
      1-3vs 4; p < 0.05), local recurrence (local recurrence (+) vs (-); p < 0.01), and
      the overexpression of FOXC2 (FOXC2 overexpression (-) vs.(+); p < 0.05). In the
      OTSCC cell line analysis, the expression of FOXC2 was also associated with
      proliferation and invasion potential. These results strongly suggest that the
      overexpression of FOXC2 may be a potent predictor of survival in OTSCC patients.

PMID- 25573595
TI  - Quality of life in patients affected by endometrial cancer: comparison among
      laparotomy, laparoscopy and vaginal approach.
AB  - The aim of this study is to verify if the surgical approach
      (laparoscopy/laparotomy/vaginal) in stage-I endometrial cancer treatment, may
      have effects on intra- and post-operative outcomes and on the patient's quality
      of life. The study group consisted of patients with histological diagnosis of
      type-I endometrial adenocarcinoma, stage-I. They were divided into three groups
      according to surgical approach chosen (laparotomic/laparoscopic/vaginal). Every
      patient answered a telephone health survey (SF-36) at 30 and 180 days post
      surgery. Surgical-operating times, hospitalization length and short/long-term
      complications after surgery were also compared. The SF-36 survey revealed a
      better performance status in patients who underwent laparoscopy as compared to
      those who received laparotomy or vaginal surgery. We found significantly better
      results considering General Health, Physical Functioning, Role-Physical and
      Bodily Pain in the laparoscopy group after 30 and 180 days. Patients who
      underwent laparoscopy had significantly shorter hospitalization and less post
      operative complications even if laparoscopy required significantly longer
      surgical-operating times compared to vaginal surgery. Our data confirm the
      superiority of the laparoscopic approach respect to the laparotomic and vaginal
      ones both in term of hospitalization length and post-operative complications.

PMID- 25573597
TI  - Mistaken identity: Legionella micdadei appearing as acid-fast bacilli on lung
      biopsy of a hematopoietic stem cell transplant patient.
AB  - Legionella micdadei is a potential cause of invasive lung infections in
      immunocompromised hosts. On biopsy specimens, it can appear as an acid-fast
      bacillus (AFB) and can be mistaken for a member of genus Mycobacterium. As
      Legionella requires selective media to grow in culture, and the commonly used,
      commercially available urine antigen test for Legionella only detects Legionella
      pneumophila serogroup-1, but not L. micdadei, it is important to consider this
      organism in the differential diagnosis for AFB in immunocompromised hosts. We
      report a case of L. micdadei infection, which was initially treated empirically
      for non-tuberculous mycobacteria based on AFB staining of biopsy tissue before
      the final diagnosis was made. 

PMID- 25573596
TI  - Amyloid-beta precursor protein: Multiple fragments, numerous transport routes and
      mechanisms.
AB  - This review provides insight into the intraneuronal transport of the Amyloid-beta
      Precursor Protein (APP), the prototype of an extensively posttranslationally
      modified and proteolytically cleaved transmembrane protein. Uncovering the
      intricacies of APP transport proves to be a challenging endeavor of cell biology
      research, deserving increased priority, since APP is at the core of the
      pathogenic process in Alzheimer's disease. After being synthesized in the
      endoplasmic reticulum in the neuronal soma, APP enters the intracellular
      transport along the secretory, endocytic, and recycling routes. Along these
      routes, APP undergoes cleavage into defined sets of fragments, which themselves
      are transported - mostly independently - to distinct sites in neurons, where they
      exert their functions. We review the currently known routes and mechanisms of
      transport of full-length APP, and of APP fragments, commenting largely on the
      experimental challenges posed by studying transport of extensively cleaved
      proteins. The review emphasizes the interrelationships between the proteolytic
      and posttranslational modifications, the intracellular transport, and the
      functions of the APP species. A goal remaining to be addressed in the future is
      the incorporation of the various views on APP transport into a coherent picture.
      In this review, the disease context is only marginally addressed; the focus is on
      the basic biology of APP transport under normal conditions. As shown, the studies
      of APP transport uncovered numerous mechanisms of transport, some of them
      conventional, and others, novel, awaiting exploration.

PMID- 25573598
TI  - Anatomical features and management of bioresorbable vascular scaffolds failure: A
      case series from the GHOST registry.
AB  - The Absorb bioresorbable vascular scaffold (Absorb BVS, Abbott Vascular, Santa
      Clara, California) promises to address some of the residual shortcomings of
      existing metallic stents, such as late events induced by permanent caging of the
      coronary vessel. Scaffold restenosis (ScR) of BVS has been poorly described so
      far and treatment strategies for this event remain to be codified. We report on a
      case series of 14 lesions in 12 patients presenting with ScR and discuss their
      anatomical features and management strategies. (c) 2015 Wiley Periodicals, Inc. 

PMID- 25573599
TI  - Personal factors in systemic sclerosis and their coverage by patient-reported
      outcome measures. A multicentre European qualitative study and literature review.
AB  - BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease where thickening of
      the skin can lead to reduced body function and limitations in activities. Severe
      forms can also affect and seriously damage inner organs. Patient-centred
      rehabilitation emphasises considerations of patients' background, experience and
      behavior which highlights the need to know if patient-reported outcome measures
      (PROMs) include such personal factors. AIM: To identify and describe personal
      factors in the experiences of functioning and health of persons with SSc and to
      examine if and to what extent PROMs in SSc research cover these factors. DESIGN:
      Data from a qualitative study with focus group interviews were analysed. PROMs in
      SSc research were identified in a literature review between 2008-2013. SETTING:
      Participants were recruited from outpatient clinics at rheumatology department.
      POPULATION: Sixty-three patients with SSc from four European countries
      participated. METHODS: Data from interviews were analysed using a structure of
      personal factors developed by Geyh et al. Identified PROMs were analysed and
      linked to main concepts, related to the personal factors, found in the interview
      data. RESULTS: Nineteen main concepts were related to the area "patterns of
      experience and behaviour" in the personal factor structure, 16 to "thoughts and
      beliefs", nine to "feelings", one to "motives" and one to "personal history and
      biography", respectively. Among the 35 PROMs identified, 15 did not cover any of
      the identified concepts. Concepts within the area "feelings" were mostly covered
      by the PROMs. Five of the PROMs covered "patterns of experience and behaviour",
      while "motives" and "personal history and biography" were not covered at all.
      Four of the identified PROMs covered concepts within the areas "feelings",
      "thoughts and beliefs" and "patterns of experience and behaviour" in the same
      instrument. The Illness Cognition Questionnaire and Illness Behaviour
      Questionnaire were such PROMs. CONCLUSION: Patterns of experience and behaviour
      had the highest number of concepts related to personal factors, but few of the
      PROMs in SSc research covered these factors. Only a few PROMs covered several
      personal factors areas in the same instrument. CLINICAL REHABILITATION IMPACT:
      The results would be of value when developing core sets for outcome measurements
      in SSc.

PMID- 25573600
TI  - Normalization of Functional Independence Measure variation improves assessment of
      stroke rehabilitation outcome.
AB  - BACKGROUND: Assessment of rehabilitation outcome is based on measuring the change
      in Functional Independence Measure (FIMTM) score between the start and end of
      rehabilitation. However, the raw FIMTM score gain is subject to a ceiling effect.
      Proposed solutions to this problem have incongruities that limit their use. AIM:
      The aim of this study was to determine the factors that influence functional
      outcome in stroke rehabilitation, exploring the possibility of developing an
      outcome index free of the ceiling effect and of the incongruities revealed by the
      proposed solutions. DESIGN: Retrospective study of the electronic clinical
      records of patients admitted to a rehabilitation unit over a period of 5 years.
      SETTING: Rehabilitation unit. POPULATION: A total of 224 patients admitted for
      first post-stroke rehabilitation of either ischaemic or hemorrhagic etiology.
      METHODS: Rehabilitation outcome was evaluated based on changes in both raw and
      "normalized" FIMTM motor and cognitive scores observed between hospital admission
      and discharge. Normalized differences are in the range 0-1 and may be considered
      an estimate of the actually attained fraction of the maximum expected recovery,
      while the modified algebraic formula (+1 to both numerator and denominator) is
      intended to correct the incongruities observed in available solutions. Seventeen
      prognostic factors were selected as possible effect modifiers of the outcome. A
      multivariable model-building strategy, based on fractional polynomials, was
      adopted to select the significant factors, and the stability of the results.
      RESULTS: The procedure adopted to normalize both FIMTM outcomes resolves the
      ceiling effect and corrects the incongruities noted with available solutions. The
      level of disability at admission is confirmed as the strongest prognostic factor
      associated with both cognitive and motor outcomes. The onset-admission interval
      negatively influence motor recovery, bat not cognitive one. CONCLUSION: There is
      strong evidence to support the proposal that it is advantageous to measure
      functional recovery by means of the normalized change in FIMTM score. Following a
      rehabilitation programme, functional recovery should be evaluated separately for
      motor and cognitive domains. Rehabilitation program should begin as soon as
      possible. CLINICAL REHABILITATION IMPACT: Improved assessment of rehabilitation
      outcome leads to increased achievement of a favourable treatment outcome.

PMID- 25573601
TI  - Clinical scales for measuring stroke rehabilitation promote functional recovery
      by supporting teamwork.
AB  - BACKGROUND: The growing interest in documenting the effectiveness of
      rehabilitation has led to a progressive increasing focus on clinical tools to
      measure stroke-survivors disability and recovery. In clinical practice a general
      agreement on the instruments to be used seems to be lacking and clinical scales
      are often limited to the assessment of global function. AIM: The study
      investigated whether the use of a selection of clinical scales/scores added to a
      single global measure during rehabilitation care, may lead to a better functional
      outcome for stroke inpatients. DESIGN: Retrospective study. SETTING:
      Neurorehabilitation inpatients. POPULATION: Consecutive patients affected by
      first-ever stroke. METHODS: Patients in the control group (CG) (N.=139) were
      assessed at admission and at discharge with the Functional Independence Measure
      (FIM), while patients in the study group (SG) (N.=127) were evaluated by means of
      a basic core-set of clinical scales/scores as well as with the FIM. Patients in
      both groups were evaluated and treated by the same multiprofessional team,
      following the same rehabilitative treatment approaches. RESULTS: At discharge
      both groups significantly improved at the FIM total Score, compared to the
      admission; a significant improvement was also reported for all the clinical
      scales in SG. However, the CG showed longer length of stay (LOS) than the SG and
      between-group analysis revealed statistical significant differences in the FIM
      total score, in the FIM gain and in all the indices of performance (FIM
      efficiency, FIM absolute efficacy, FIM relative efficacy), in favor of the SG.
      CONCLUSIONS: The use of a selection of scales added to a global functional
      measure, allows a better definition of both the person's profile of disability
      and the rehabilitative goals, and is associated to a better functional outcome at
      discharge. CLINICAL REHABILITATION IMPACT: Clinical scales may be used in
      clinical practice to better define the person's profile of disability, allowing
      the design of patient tailored goals, and to favor team working.

PMID- 25573602
TI  - Do aerobic exercises really improve aerobic capacity of stroke survivors? A
      systematic review and meta-analysis.
AB  - BACKGROUND: Even if aerobic exercises are recommended to stroke survivors, the
      clinical significance of the effect of these exercises on aerobic capacity has
      not been definitely shown. AIM: To investigate, if there is evidence that aerobic
      capacity, measured by maximal oxygen consumption, can be improved by aerobic
      training? DESIGN: Systematic review and meta-analysis, all settings. SETTING:
      Department of Physical and Rehabilitation Medicine of a University Hospital.
      POPULATION: Adult stroke survivors. METHODS: Search on CENTRAL, MEDLINE, EMBASE,
      CINAHL, Pedro. Study selection and extraction based on the Cochrane Handbook for
      Systematic Reviews. Random effects meta-analysis. RESULTS: Based on 13 randomized
      aerobic training improved aerobic capacity on average by 2.5 mL/kg/min. Four of
      the included studies had low risk of bias. CONCLUSIONS: There is strong evidence
      that aerobic training is capable of improving aerobic capacity of stroke
      survivors, supporting the routine recommendation for training after stroke.
      CLINICAL REHABILITATION IMPACT: It is not known, if one type of training is more
      effective than others in stroke survivors.

PMID- 25573603
TI  - Platinum-carbide interactions: core-shells for catalytic use.
AB  - A selection of carbides (TiC, NbC, TaC, WC and SiC) have been studied using
      density functional theory. Their calculated adsorption characteristics towards Pt
      overlayers are presented with a view to the use of the carbides as core-shell
      components. WC hcp and SiC are observed to support Pt overlayers on all surfaces
      making them promising candidates for full Pt encapsulation. Pt adsorption on fcc
      (111) carbide surfaces is observed to take place with the transition metal
      surface resonances (TMSRs) playing a key role whilst fcc (100) are universally
      unfavourable towards Pt adsorption. The effect of the carbide supports on oxygen
      binding on the Pt overlayer is also considered and discussed in relation to the
      oxygen reduction reaction (ORR). The oxygen adsorption study revealed several Pt
      WC surfaces which exhibit reduced oxygen adsorption energies, suggesting they
      should promote or maintain ORR activity with respect to nanoparticulate Pt
      catalysts. 

PMID- 25573604
TI  - A ring-flippable sugar as a stimuli-responsive component of liposomes.
AB  - For the development of a liposome that takes in and out a drug in response to
      stimuli, 2,4-diaminoxylose (Xyl), which allows stimuli-responsive conformational
      switches between (4)C1 and (1)C4, was incorporated into a lipid structure: Xyl
      derivatives with C8 and C16 methylene chains at the 1,3-positions (C8Xyl and
      C16Xyl) were synthesized. (1)H NMR spectroscopy indicates that the addition of
      Zn(2+) and then H(+) induces conformational switches from the chair ((4)C1) to
      the reverse chair ((1)C4) and (1)C4-to-(4)C1, respectively, at Xyl; this leads to
      transformation of the lipids between linear and bent structures. Osmotic pressure
      and electron microscopy studies demonstrate that C8Xyl in water forms spherical
      solid aggregates (C8Xyl-Zn), which are converted into liposomes (C8Xyl+Zn) upon
      the addition of Zn(2+), and C16Xyl forms liposomes regardless of the presence of
      Zn(2+). The aggregates of C8Xyl+/-Zn incorporated a fluorophore and only C8Xyl+Zn
      released the content upon the addition of HCl. This study shows that Xyl could be
      a stimuli-responsive component of a liposome.

PMID- 25573606
TI  - Bromelain: a natural proteolytic for intra-abdominal adhesion prevention.
AB  - INTRODUCTION: Peritoneal adhesions are pathological fibrous connections between
      peritoneal surfaces resulting from incomplete peritoneal repair. Adhesions cause
      various health problems ranging from pelvic pain and bowel obstruction to
      infertility. To date, no effective agent exists for intra-abdominal adhesion
      prevention. Bromelain is the crude extract of the pineapple and it has
      fibrinolytic, antithrombotic, and anti-inflammatory properties. Bromelain has
      been shown to be effective for removing necrotic tissues and has been found to be
      effective for treating various wounds, inflammatory conditions, and thrombotic
      pathologies. In the present study, we evaluated bromelain as a novel agent for
      preventing intra-abdominal adhesions. METHODS: Group 1 (control group): Adhesions
      were produced by cecal abrasion method, and no treatment was applied. Group 2
      (i.p. bromelain-treated group): After adhesion formation, 10 mg/kg/BW of
      bromelain dissolved in 1 mL saline solution was applied intraperitoneally for 10
      days. Group 3 (i.p. saline-treated group): After adhesion formation, 1 mL saline
      solution was applied intraperitoneally for 10 days. On postoperative day 10, all
      animals were sacrificed. RESULTS: All 30 rats survived surgery. Throughout the
      follow-up period, no complications were observed. Statistically significant
      differences were found between the groups with regards to macroscopic adhesion
      scores, inflammation, fibrosis and neo-vascularization (p < 0.001, <0.001, p =
      0.001, p = 0.002, respectively). Macroscopic and histopathologic (inflammation,
      fibrosis, neo-vascularization) adhesion scores were lowest in the bromelain
      treated group. CONCLUSION: Bromelain, acting through its barrier, anti
      inflammatory, antioxidant, and proteolytic effects and without increasing
      bleeding tendency or having any adverse effects on wound healing, may be a
      suitable agent for intra-abdominal adhesion prevention.

PMID- 25573607
TI  - Neuroendocrine Merkel cell nodal carcinoma of unknown primary site: management
      and outcomes of a rare entity.
AB  - Merkel cell nodal carcinoma of unknown primary (MCCUP) is a rare neuroendocrine
      tumour with distinct clinical and biological behaviour. We conducted a review of
      retrospective data extracted from 90 patients focusing on the management and
      outcome of this disease. We also compared life expectancy of these patients with
      the outcome of patients with known Merkel primaries and with neuroendocrine
      cancers of unidentifiable primary. There is a limited body of data for this type
      of malignancy, however, patients with Merkel cell nodal carcinoma of unknown
      primary site, seem to have better survival when treated aggressively than
      patients with cutaneous Merkel tumours of the same stage and equal survival with
      patients with low-grade neuroendocrine tumour of unknown origin. The lack of
      prospective trials, and the inadequate data, hamper the management of these
      tumours. Establishment of treatment guidelines is urgently needed. 

PMID- 25573605
TI  - Prospective longitudinal evaluation of emotional and behavioral functioning in
      pediatric patients with low-grade glioma treated with conformal radiation
      therapy.
AB  - Patients with low-grade glioma (LGG) who are successfully treated with
      irradiation are at increased risk for cognitive and psychosocial late effects.
      Conformal radiation therapy (CRT) allows sparing of cognitive deficits, but how
      it affects emotional and behavioral functioning remains unclear. We performed a
      prospective longitudinal study of the emotional and behavioral functioning of
      pediatric patients with LGG in the first 5 years post-CRT. Ninety-five pediatric
      patients with LGG treated on an institutional Phase II trial (August 1997-June
      2009) underwent neuropsychological assessments pre-CRT and 6, 12, 24, 36, 48, and
      60 months post-CRT. Parent-reported scores on the Child Behavior Checklist (CBCL)
      were analyzed. Three competence scales (School Competence, Social Competence, and
      Activities), two summary scales (Internalizing Problems and Externalizing
      Problems), and two subscales of theoretical interest (Attention Problems and
      Social Problems) from the CBCL were used. Among 80 eligible patients [44 female,
      68 white], 51 had pilocytic astrocytoma and 13 had optic pathway glioma. Mean age
      at diagnosis was 6.8 years (SD = 4.3 years) and at CRT initiation was 8.9 years
      (SD = 3.4 years). Before CRT, deficits were demonstrated on the competence scales
      (mean scores below normative mean) and the Attention Problems and Social Problems
      subscales (mean scores above normative means). This trend continued at 5 years
      post-CRT. Longitudinal trajectories of emotional and behavioral functioning were
      stable over 5 years. Emotional and behavioral deficits remain relatively stable
      over the 5 years post-CRT in patients with LGG, suggesting that CRT may not
      exacerbate pre-existing psychosocial difficulties in this population.

PMID- 25573608
TI  - [Corrigendum] Overexpression of the chimeric plasmin-resistant VEGF165/VEGF183
      (132-158) protein in murine breast cancer induces distinct vascular patterning
      adjacent to tumors and retarded tumor growth.

PMID- 25573609
TI  - Caspases come together over LPS.
AB  - Caspases are cellular executors, initiating cell death. In a recent study, Shi et
      al. report that caspases 4/5/11 are cytosolic LPS receptors, becoming activated
      through oligomerization upon interaction with LPS. These findings shed new light
      on the mechanisms underlying caspase-mediated pyroptosis, and have implications
      for the development of effective drugs to treat sepsis. 

PMID- 25573610
TI  - River transport of mercury from artisanal and small-scale gold mining and risks
      for dietary mercury exposure in Madre de Dios, Peru.
AB  - Artisanal and small-scale gold mining (ASGM) is a major contributor to
      deforestation and the largest anthropogenic source of atmospheric mercury
      worldwide. Despite significant information on the direct health impacts of
      mercury to ASGM miners, the impact of mercury contamination on downstream
      communities has not been well characterized, particularly in Peru's Madre de Dios
      region. In this area, ASGM has increased significantly since 2000 and has led to
      substantial political and social controversy. This research examined the spatial
      distribution and transport of mercury through the Madre de Dios River with
      distance from ASGM activity. This study also characterized risks for dietary
      mercury exposure to local residents who depend on fish from the river. River
      sediment, suspended solids from the water column, and fish samples were collected
      in 2013 at 62 sites near 17 communities over a 560 km stretch of the Madre de
      Dios River and its major tributaries. In areas downstream of known ASGM activity,
      mercury concentrations in sediment, suspended solids, and fish within the Madre
      de Dios River were elevated relative to locations upstream of mining. Fish tissue
      mercury concentrations were observed at levels representing a public health
      threat, with greater than one-third of carnivorous fish exceeding the
      international health standard of 0.5 mg kg(-1). This study demonstrates that
      communities located hundreds of kilometers downstream of ASGM activity, including
      children and indigenous populations who may not be involved in mining, are at
      risk of dietary mercury exposure that exceed acceptable body burdens. This report
      represents the first systematic study of the region to aid policy decision-making
      related to ASGM activities in Peru. 

PMID- 25573611
TI  - [Eosinophilia and lungs infiltrates in patient originating from Senegal].

PMID- 25573612
TI  - [Visual disturbances as a sign of early neurosyphilis. Two cases of
      neurosyphilis].

PMID- 25573613
TI  - [Trouser size as a reliable estimate of waist circumference].

PMID- 25573614
TI  - [Management of a first depressive episode in the primary care setting. Use of
      antidepressants and referrals].
AB  - INTRODUCTION: The majority of patients who have a first depressive episode are
      treated by Primary Care physicians. The aim of this study was to evaluate the use
      of antidepressants and referrals to mental health and the treatment modifications
      made by psychiatrists. MATERIAL AND METHODS: A descriptive, retrospective study
      was conducted on patients from 64 Primary Care clinics, distributed in five
      Spanish provinces. The clinical history data, regarding use of antidepressants,
      criteria for referral, and response of psychiatric services were evaluated from
      June 2008 to June 2011. RESULTS: The study included 324 patients. The most
      commonly prescribed medication was escitalopram, with selective serotonin
      reuptake inhibitors (SSRI) making up 73.5% of the total. More than two-thirds
      (69.7%) of the patients were on treatment for at least 6 months, with no reason
      recorded for the 40.4% drop-outs. A large majority of professionals (76.9%) wait
      at least 3 weeks before modifying the medication, especially changing
      antidepressant. The Primary Care physicians referred 39.2% of patients to
      psychiatry, although much of these referrals (43.9%) had no justification. There
      was a lower referral rate to psychology (23.1%). An antidepressant was given to a
      large number of patients on multiple medications, without taking into account the
      risk of interactions in a high percentage. CONCLUSIONS: The Primary Care
      physician appropriately uses the antidepressants of the first choice, but does
      not pay attention to the risks in complex patients. There must be an appropriate
      duration of treatment and an improvement of the criteria for referral to mental
      health services.

PMID- 25573615
TI  - Novel method for online monitoring of dissolved N2O concentrations through a gas
      stripping device.
AB  - Nitrous oxide emissions from wastewater treatment plants are currently measured
      by online gas phase analysis or grab sampling from the liquid phase. In this
      study, a novel method is presented to monitor the liquid phase N2O concentration
      for aerated as well as non-aerated conditions/reactors, following variations both
      in time and in space. The monitoring method consists of a gas stripping device,
      of which the measurement principle is based on a continuous flow of reactor
      liquid through a stripping flask and subsequent analysis of the N2O concentration
      in the stripped gas phase. The method was theoretically and experimentally
      evaluated for its fit for use in the wastewater treatment context. Besides, the
      influence of design and operating variables on the performance of the gas
      stripping device was addressed. This method can easily be integrated with online
      off-gas measurements and allows to better investigate the origin of the gas
      emissions from the treatment plant. Liquid phase measurements of N2O are of use
      in mitigation of these emissions. The method can also be applied to measure other
      dissolved gasses, such as methane, being another important greenhouse gas. 

PMID- 25573616
TI  - Sports injuries and illnesses during the European Youth Olympic Festival 2013.
AB  - BACKGROUND: The European Youth Olympic Festival (EYOF) is a biennial sporting
      event of nine Olympic Summer Sports for talented athletes, aged 13-18 years, from
      all over Europe. OBJECTIVE: To analyse the injuries and illnesses that occurred
      during the multisport event (14-19 July 2013), with the long-term aim of enabling
      international sports federations, the National Olympic Committees, and the
      European Olympic Committee to improve protection of athletes' health in youth.
      METHODS: Daily occurrence or non-occurrence of injuries and illnesses was
      recorded by using the IOC injury and illness surveillance system for multisport
      events. All National Olympic Committee physicians and healthcare providers and
      physicians of the Local Organizing Committee were invited to participate.
      RESULTS: In total, 2272 athletes from 49 countries took part in the EYOF 2013.
      During the five competition days of EYOF, 207 injuries and 46 illnesses were
      reported, resulting in an incidence of 91.1 injuries and 20.2 illnesses per 1000
      athletes. Almost 10% of the athletes sustained at least one injury or illness.
      CONCLUSIONS: This study is the first multisport surveillance study on injuries
      and illnesses during the EYOF or any other summer Games organised for youth elite
      athletes. The data form the basis for further research on risk factors and injury
      mechanisms for this cohort. This research is needed to gain more knowledge and
      finally to implement effective injury and illness prevention measures.

PMID- 25573617
TI  - Effect of sedentary activity on telomere length may not be so straightforward.

PMID- 25573618
TI  - Performance of genotypic tools for prediction of tropism in HIV-1 subtype C V3
      loop sequences.
AB  - Currently, there is no consensus on the genotypic tools to be used for tropism
      analysis in HIV-1 subtype C strains. Thus, the aim of the study was to evaluate
      the performance of the different V3 loop-based genotypic algorithms available. We
      compiled a dataset of 645 HIV-1 subtype C V3 loop sequences of known coreceptor
      phenotypes (531 R5-tropic/non-syncytium-inducing and 114 X4-tropic/R5X4
      tropic/syncytium-inducing sequences) from the Los Alamos database
      (http://www.hiv.lanl.gov/) and previously published literature. Coreceptor usage
      was predicted based on this dataset using different software-based machine
      learning algorithms as well as simple classical rules. All the sophisticated
      machine-learning methods showed a good concordance of above 85%. Geno2Pheno
      (false-positive rate cutoff of 5-15%) and CoRSeqV3-C were found to have a high
      predicting capability in determining both HIV-1 subtype C X4-tropic and R5-tropic
      strains. The current sophisticated genotypic tropism tools based on V3 loop
      perform well for tropism prediction in HIV-1 subtype C strains and can be used in
      clinical settings.

PMID- 25573620
TI  - Hepatic vein thrombosis associated with segmental hypo-attenuation in the liver:
      an unusual complication of a haemodialysis catheter.

PMID- 25573619
TI  - Schizandrin ameliorates ovariectomy-induced memory impairment, potentiates
      neurotransmission and exhibits antioxidant properties.
AB  - BACKGROUND AND PURPOSE: Schizandrin (SCH) has been reported to prevent or reduce
      learning and memory defects. However, it is not known whether SCH ameliorates
      cognitive impairments induced by oestrogen deficiency. In the present study, we
      investigated the effect of SCH on memory in ovariectomized (OVX) and non-OVX
      rats. EXPERIMENTAL APPROACH: A passive avoidance test was used to evaluate the
      effect of SCH on memory. Field EPSPs were recorded in hippocampal slices using an
      electrophysiological method. In OVX rats, biochemical parameters in the bilateral
      hippocampus were measured; these included superoxide dismutase (SOD),
      malondialdehyde (MDA) and AChE. Also, the number of NADPH-diaphorase (NADPH-d)
      positive neurons was counted by NADPH-d histochemistry staining technique. KEY
      RESULTS: Oral SCH improved the memory and facilitated the induction of long-term
      potentiation in non-OVX and OVX rats; this effect was more obvious in OVX rats.
      Similarly, SCH perfusion enhanced synaptic transmission in hippocampal slices
      from both non-OVX and OVX rats. However, SCH perfusion reduced the ratio of
      paired-pulse facilitation only in OVX but not in non-OVX rats. In addition, SCH
      decreased AChE activity and MDA level and increased SOD activity and the number
      of NADPH-d-positive neurons in OVX rats. CONCLUSIONS AND IMPLICATIONS: SCH
      improves memory in OVX rats and its potential mechanisms may include a reduction
      in the loss of hippocampal NADPH-d positive neurons, an increase of antioxidant
      properties and a potentiation of synaptic transmission that possibly involves to
      enhance cholinergic function. Overall, our findings indicate that SCH has
      potential as a therapeutic strategy for the cognitive dysfunctions associated
      with the menopause.

PMID- 25573621
TI  - FGF-23 levels in patients with critical carotid artery stenosis.
AB  - The aim of this study was to evaluate fibroblast growth factor (FGF)-23 serum
      levels and its tissue expression in patients with critical carotid artery
      stenosis (CAS). We selected 35 patients with critical CAS undergoing carotid
      thromboendoarterectomy. In each patient, FGF-23 serum levels were evaluated just
      prior to the surgery (t0) and 30 min (t1) thereafter. Moreover, macrophage
      cytokines were measured at baselines. Carotid artery specimens were used for
      immune histochemistry. On the basis of the histology, the patients were divided
      into 2 groups: A with complicated plaque and B with uncomplicated plaque. Twenty
      complicated plaques (57.14%, group A,) and 15 uncomplicated (42.86%, group B)
      were evaluated: calcifications were present in 16/20 (80%) complicated plaques
      and in 6/15 (40%) uncomplicated plaques. An inflammatory infiltrate was observed
      in 26/35 carotid samples: 18/26 (69.23%) complicated and 8/26 (30.76%)
      uncomplicated. FGF-23(+) cells were present in 17/20 complicated (85%) and in 8
      uncomplicated (53%) plaques. The double-staining immunofluorescence confirmed
      that macrophage cells (CD68(+)) were also positive for FGF-23 staining. Serum
      levels of FGF-23 were significantly higher in group A versus group B at t0 (p <
      0.05) and t1 (p 0.0047). Moreover, in group A patients a significant increase of
      FGF-23 serum levels was observed at t1 in comparison with t0 (p 0.0011). Our
      results suggest that FGF-23 acts in the late phases of atherosclerotic disease
      and may potentially represent a marker of complications in critical CAS.

PMID- 25573623
TI  - Identification of hub subnetwork based on topological features of genes in breast
      cancer.
AB  - The aim of this study was to provide functional insight into the identification
      of hub subnetworks by aggregating the behavior of genes connected in a protein
      protein interaction (PPI) network. We applied a protein network-based approach to
      identify subnetworks which may provide new insight into the functions of pathways
      involved in breast cancer rather than individual genes. Five groups of breast
      cancer data were downloaded and analyzed from the Gene Expression Omnibus (GEO)
      database of high-throughput gene expression data to identify gene signatures
      using the genome-wide global significance (GWGS) method. A PPI network was
      constructed using Cytoscape and clusters that focused on highly connected nodes
      were obtained using the molecular complex detection (MCODE) clustering algorithm.
      Pathway analysis was performed to assess the functional relevance of selected
      gene signatures based on the Kyoto Encyclopedia of Genes and Genomes (KEGG)
      database. Topological centrality was used to characterize the biological
      importance of gene signatures, pathways and clusters. The results revealed that,
      cluster1, as well as the cell cycle and oocyte meiosis pathways were significant
      subnetworks in the analysis of degree and other centralities, in which hub nodes
      mostly distributed. The most important hub nodes, with top ranked centrality,
      were also similar with the common genes from the above three subnetwork
      intersections, which was viewed as a hub subnetwork with more reproducible than
      individual critical genes selected without network information. This hub
      subnetwork attributed to the same biological process which was essential in the
      function of cell growth and death. This increased the accuracy of identifying
      gene interactions that took place within the same functional process and was
      potentially useful for the development of biomarkers and networks for breast
      cancer. 

PMID- 25573624
TI  - The present of presence.

PMID- 25573622
TI  - Advanced therapies in patients with congenital heart disease-related pulmonary
      arterial hypertension: results from a long-term, single center, real-world follow
      up.
AB  - Pulmonary arterial hypertension (PAH) is a common finding in patients with
      congenital heart disease (CHD), and has relevant prognostic implications. The
      recent introduction of advanced therapies (AT) considerably improved the clinical
      outcome of these patients, but real-world data are still lacking. We aimed at
      reporting the results of a long-term follow-up of CHD patients with PAH
      undergoing AT, followed at a tertiary Center during the two last decades. The
      study population included a total of 34 patients with an established diagnosis of
      CHD-related PAH. In addition to conventional treatment, 97% of patients started
      AT during the follow-up. Over a median follow-up of 9 [3-31] years, 11 (32.4%)
      patients died: 7 of them were affected by Eisenmenger syndrome and the majority
      of patients were in NYHA class >=3 at the time of death. Among the 23 patients
      who were alive at the last follow-up, the majority were in NYHA class I-II.
      Oxygen saturation and 6-min walking distance improved in all subjects within the
      first 6 months after starting of AT. One patient with ventricular septum defect
      and high pulmonary resistances was successfully treated with AT to lower
      resistances and underwent defect closure. A good clinical outcome was also
      observed in the subset (n = 8) with Down syndrome. The results of this real-world
      experience suggest that, despite a relatively high mortality rate mostly related
      to late commencement of AT, the clinical outcome of subjects with CHD-related PAH
      undergoing AT are characterized by a good quality of life and clinical
      improvement in most patients.

PMID- 25573625
TI  - Comparison of the expression levels of molecular markers among the peripheral
      area and central area of primary tumor and metastatic lymph node tumor in
      patients with squamous cell carcinoma of the lung.
AB  - PURPOSE: Immunohistochemical analysis for the identification of clinically
      relevant biomarkers is important. However, there have been no detailed reports
      about the heterogeneous expressions of the various markers in squamous cell
      carcinoma of the lung. METHODS: A total of 113 patients with squamous cell
      carcinoma of the lung with lymph node metastasis were included. The expression
      levels of 9 molecules (E-cadherin, S100A4, CD44, ALDH1, SOX2, EGFR, HER2, FGFR1
      and VEGFR2) in the peripheral area and central area of primary tumor and
      metastatic lymph nodes were evaluated by immunohistochemistry. The differences in
      the staining scores of these molecules among the three areas were assessed. We
      also analyzed the relationships between the expression levels of these molecules
      and the recurrence-free survival. RESULTS: The E-cadherin expression was higher
      in the central area than in the peripheral area and metastatic lymph nodes
      (median staining score: 60 vs. 50, 30); the CD44 expression was higher in the
      central area than in the metastatic lymph nodes (117 vs. 90); and the EGFR
      expression was higher in the central area than in the peripheral area and
      metastatic lymph nodes (163 vs. 130, 110). Low CD44 expression in the central
      area, low EGFR expression in the peripheral area and high SOX2 expression in the
      metastatic lymph nodes were associated with a shorter recurrence-free survival (p
      < 0.01, p = 0.02, p = 0.03, respectively). CONCLUSIONS: Our findings confirmed
      that some molecular markers exhibited different expression levels in anatomically
      different areas and suggested that area-by-area immunohistochemical analysis for
      biomarkers may provide useful information for more precise prediction of the
      recurrence.

PMID- 25573626
TI  - Nasal oxytocin administration reduces food intake without affecting locomotor
      activity and glycemia with c-Fos induction in limited brain areas.
AB  - Recent studies have considered oxytocin (Oxt) as a possible medicine to treat
      obesity and hyperphagia. To find the effective and safe route for Oxt treatment,
      we compared the effects of its nasal and intraperitoneal (IP) administration on
      food intake, locomotor activity, and glucose tolerance in mice. Nasal Oxt
      administration decreased food intake without altering locomotor activity and
      increased the number of c-Fos-immunoreactive (ir) neurons in the paraventricular
      nucleus (PVN) of the hypothalamus, the area postrema (AP), and the dorsal motor
      nucleus of vagus (DMNV) of the medulla. IP Oxt administration decreased food
      intake and locomotor activity and increased the number of c-Fos-ir neurons not
      only in the PVN, AP, and DMNV but also in the nucleus of solitary tract of the
      medulla and in the arcuate nucleus of the hypothalamus. In IP glucose tolerance
      tests, IP Oxt injection attenuated the rise of blood glucose, whereas neither
      nasal nor intracerebroventricular Oxt affected blood glucose. In isolated islets,
      Oxt administration potentiated glucose-induced insulin secretion. These results
      indicate that both nasal and IP Oxt injections reduce food intake to a similar
      extent and increase the number of c-Fos-ir neurons in common brain regions. IP
      Oxt administration, in addition, activates broader brain regions, reduces
      locomotor activity, and affects glucose tolerance possibly by promoting insulin
      secretion from pancreatic islets. In comparison with IP administration, the nasal
      route of Oxt administration could exert a similar anorexigenic effect with a
      lesser effect on peripheral organs.

PMID- 25573627
TI  - Is it time for an Australian advanced practice framework for occupational
      therapists?

PMID- 25573628
TI  - A fluorescent heteroditopic hemicryptophane cage for the selective recognition of
      choline phosphate.
AB  - The first fluorescent hemicryptophane cage was synthesized and developed as an
      efficient and selective sensor for choline phosphate. The heteroditopic character
      of the host in the recognition process was evidenced. NMR experiments highlight a
      full encapsulation of the guest, inducing the chiralisation-like behavior of the
      achiral choline phosphate. 

PMID- 25573629
TI  - Current status and future role of brain PET/MRI in clinical and research
      settings.
AB  - Hybrid PET/MRI systematically offers a complementary combination of two
      modalities that has often proven itself superior to the single modality approach
      in the diagnostic work-up of many neurological and psychiatric diseases. Emerging
      PET tracers, technical advances in multiparametric MRI and obvious workflow
      advantages may lead to a significant improvement in the diagnosis of dementia
      disorders, neurooncological diseases, epilepsy and neurovascular diseases using
      PET/MRI. Moreover, simultaneous PET/MRI is well suited to complex studies of
      brain function in which fast fluctuations of brain signals (e.g. related to task
      processing or in response to pharmacological interventions) need to be monitored
      on multiple levels. Initial simultaneous studies have already demonstrated that
      these complementary measures of brain function can provide new insights into the
      functional and structural organization of the brain. 

PMID- 25573630
TI  - PET imaging biomarkers in head and neck cancer.
AB  - In locally advanced head and neck squamous cell carcinoma (HNSCC), the role of
      imaging becomes more and more critical in the management process. In this
      framework, molecular imaging techniques such as PET allow noninvasive assessment
      of a range of tumour biomarkers such as metabolism, hypoxia and proliferation,
      which can serve different purposes. First, in a pretreatment setting they can
      influence therapy selection strategies and target delineation for radiation
      therapy. Second, their predictive and/or prognostic value could help enhance the
      therapeutic ratio in the management of HNSCC. Third, treatment modification can
      be performed through the generation of a molecular-based heterogeneous dose
      distribution with dose escalation to the most resistant parts of the tumour, a
      concept known as dose painting. Fourth, they are increasingly becoming a tool for
      monitoring response to therapy. In this review, PET imaging biomarkers used in
      the routine management of HNSCC or under investigation are discussed. 

PMID- 25573631
TI  - FDG PET/CT imaging as a biomarker in lymphoma.
AB  - FDG PET/CT has changed the management of FDG-avid lymphoma and is now recommended
      as the imaging technique of choice for staging and restaging. The need for
      tailoring therapy to reduce toxicity in patients with a favourable outcome and
      for improving treatment in those with high-risk factors requires accurate
      diagnostic methods and a new prognostic algorithm to identify different risk
      categories. New drugs are used in relapsed/refractory patients. The role of FDG
      PET/CT as a biomarker in this context is summarized in this review. New trends in
      FDG metabolic imaging in lymphoma are addressed including metabolic tumour volume
      measurement at staging and integrative PET which combines PET data with clinical
      and molecular markers or other imaging techniques. The quantitative approach for
      response assessment which is under investigation and is used in large ongoing
      trials is compared with visual criteria. The place of FDG in the era of targeted
      therapy is discussed. 

PMID- 25573633
TI  - Breast infiltration by relapsed acute lymphoblastic leukaemia on FDG PET/CT.

PMID- 25573632
TI  - Image-derived biomarkers and multimodal imaging strategies for lung cancer
      management.
AB  - Non-small-cell lung cancer is the most common type of lung cancer and one of the
      leading causes of cancer-related death worldwide. For this reason, advances in
      diagnosis and treatment are urgently needed. With the introduction of new, highly
      innovative hybrid imaging technologies such as PET/CT, staging and therapy
      response monitoring in lung cancer patients have substantially evolved. In this
      review, we discuss the role of FDG PET/CT in the management of lung cancer
      patients and the importance of new emerging imaging technologies and radiotracer
      developments on the path to personalized medicine. 

PMID- 25573634
TI  - [177Lu]Lutetium-labelled PSMA ligand-induced remission in a patient with
      metastatic prostate cancer.

PMID- 25573636
TI  - Comparison of intra-operative 0.02% mitomycin C and sutureless limbal
      conjunctival autograft fixation in pterygium surgery: five-year follow-up.
AB  - PURPOSE: To compare efficacy and safety between fibrin sealant assisted limbal
      conjunctival autograft fixation and intra-operative MMC in pterygium surgery.
      METHODS: Prospective, comparative, interventional case series. Forty eyes of 40
      patients with nasal primary pterygium, 18 male and 22 female, were enrolled. The
      patients were assigned to two groups, and each contained nine male and 11 female
      based on the pterygium area encroaching onto the cornea. In one group, the
      conjunctival autograft was attached to the sclera with fibrin sealant, and in the
      other group, 0.02% MMC was applied after the pterygium was removed. All the
      patients were followed up postoperatively on days 1, 3, 7 and 14 then at months
      1, 2, 6, 12 and 60. The main outcome measures included operating time,
      postoperative discomfort, cornea endothelial damage, recurrence rate and
      complications. RESULTS: The average operating time was significantly shorter (p =
      0.044) in the fibrin sealant group, and fewer postoperative symptom complaints
      were received as well. On postoperative month 1, no significant differences in
      the mean endothelial cell count, mean CV and mean 6A% were observed between these
      two groups. By the end of 5-year follow-up, the recurrence rate was 0% in the
      fibrin sealant group and 20% in the MMC group (p = 0.106), and there were no
      severe visual acuity threatening complications in either group. CONCLUSION: There
      were no severe complications after long-term follow-up if intra-operative MMC was
      strictly and carefully used. Overall, this sutureless method is more effective
      than traditional MMC.

PMID- 25573637
TI  - Clinical application of endoscopic ultrasonography for esophageal achalasia.
AB  - Endoscopic ultrasonography (EUS) has been widely used for evaluating the nature
      of diseases of various organs. The possibility of applying EUS for esophageal
      motility diseases has not been well discussed despite its versatility. At
      present, peroral endoscopic myotomy (POEM) for esophageal achalasia and related
      diseases has brought new attention to esophageal diseases because POEM provides a
      more direct approach to the inner structures of the esophageal wall. In the
      present study, we discuss the clinical utility of EUS in evaluating and treating
      esophageal motility diseases such as esophageal achalasia and related diseases. 

PMID- 25573638
TI  - German Heart Report 2013.
AB  - OBJECTIVES: The 25th German Heart Report provides a comprehensive analysis of
      morbidity and mortality in patients with selected heart diseases as well as
      services and care in cardiology and cardiac surgery in Germany during the period
      2011-2012. It is the result of a multidisciplinary collaboration between the
      German Heart Foundation, the German Cardiac Society, the German Society for
      Thoracic and Cardiovascular Surgery, and the German Society of Pediatric
      Cardiology and is based on data from different sources. In addition, trends of
      the period from 1995 to 2012 are presented. RESULTS: The trends in morbidity due
      to cardiac diseases in 2010 and previous years continued in 2011. Compared with
      data from 1995 to 2010, one can observe: a slight decrease in ischemic heart
      disease in every age group; a distinct increase in valve diseases, predominantly
      at age >75 years; an increase in arrhythmias from the age of 45 years on; an
      increase in cardiac failure, especially beyond the age of 75 years. Compared with
      data from 2009, the mortality rates in 2011 differ somewhat; there is: a decrease
      in heart failure and coronary heart disease; no change in arrhythmias; a distinct
      increase in valvular heart diseases; an additional, small decrease in congenital
      heart defects. These data are in agreement with findings from other Western
      countries. Coronary heart disease, the most frequent cardiac disease, has
      continuously decreased in frequency and mortality since 2000. The underlying
      reasons are discussed. CONCLUSION: This report is an important resource for all
      parties of the healthcare system regarding heart disease conditions and their
      treatment in Germany.

PMID- 25573639
TI  - Celiac disease and bone health: just gluten free diet?
AB  - Not available. 

PMID- 25573640
TI  - Herpesviruses and breast milk.
AB  - Breast milk has always been the best source of nourishment for newborns. However,
      breast milk can carry a risk of infection, as it can be contaminated with
      bacterial or viral pathogens. This paper reviews the risk of acquisition of
      varicella-zoster virus (VZV) and cytomegalovirus (CMV), herpesviruses frequently
      detected in breastfeeding mothers, via breast milk, focusing on the clinical
      consequences of this transmission and the possible strategies for preventing it.
      Maternal VZV infections are conditions during which breastfeeding may be
      temporarily contraindicated, but expressed breast milk should always be given to
      the infant. CMV infection acquired through breast milk rarely causes disease in
      healthy term newborns; an increased risk of CMV disease has been documented in
      preterm infants. However, the American Academy of Pediatrics (AAP) does not
      regard maternal CMV seropositivity as a contraindication to breastfeeding;
      according to the AAP, in newborns weighing less than 1500 g, the decision should
      be taken after weighing the benefits of breast milk against the risk of
      transmission of infection. The real efficacy of the different methods of
      inactivating CMV in breast milk should be compared in controlled clinical trials,
      rigorously examining the negative consequences that each of these methods can
      have on the immunological and nutritional properties of the milk itself, with a
      view to establish the best risk-benefit ratio of these strategies before they are
      recommended for use in clinical practice.

PMID- 25573641
TI  - Assessment of pulmonary function in a follow-up of premature infants: our
      experience.
AB  - Respiratory diseases are a major cause of morbidity in neonates, especially
      preterm infants; a long term complication of prematurity such as bronchopulmonary
      dysplasia (BPD) is particularly relevant today. The exact role of the Pulmonary
      Function Test (PFT) in this area is not yet well defined; the PFT in newborns and
      infants - in contrast to what happens in uncooperative children and adults - are
      routinely used only in a few centers. The assessment of pulmonary function in
      newborns and infants, however, is nowadays possible with the same reliability
      that in cooperative patients with the possibility to extend the assessment of
      polmonary function from bench to bed. The assessment of pulmonary function must
      be carried out with non invasive and safe methods, at the bedside, with the
      possibility of continuous monitoring and providing adequate calculation and
      management of data. The ability to assess lung function helps to define the
      mechanisms of respiratory failure, improving the treatment and its effects and is
      therefore a useful tool in the follow-up of newborn and infant with pulmonary
      disease. 

PMID- 25573642
TI  - Surgical excision of Infantile Haemangiomas: a technical refinement to prevent
      bleeding complications.
AB  - PURPOSE: The aim of the study is to improve operative speed and precision of
      haemangiomas excision. METHODS:  CASE-REPORT: haemangioma is a common affection
      of the 8% of the population during the neonatal period. In complicated cases and
      involution sequelae surgical treatment is the first choice. The Authors propose a
      surgical refinement to prevent intraoperative bleeding. METHODS: several suture
      stitches were placed around the hemangioma. The edges of the lesion became more
      defined, thus allowing accurate excision. RESULTS AND CONCLUSIONS: Haemangiomas
      are characterized by rich blood supply. Surgery is often hindered by massive
      bleeding and Temporary placement of full-thickness sutures, surrounding the
      hemangioma, allowed a noticeable improvement in hemostasis precision and greater
      definition of the margins of the hemangioma.

PMID- 25573643
TI  - Meconial peritonitis in a rare association of partial ileal apple-peel atresia
      with small abdominal wall defect.
AB  - Intestinal atresia type III B (apple peel) and gastroschisis are both congenital
      malformations who require early surgical correction in neonatal age. Their
      association is very rare. We present the case of a full term infant with partial
      apple peel ileal atresia and a small defect of the anterior abdominal wall,
      complicated by in utero intestinal perforation and subsequent meconial
      peritonitis. We observed a partial atresia of small intestine, with involvement
      of terminal ileus savings of jejunum and a large part of the proximal ileum,
      small anterior abdominal wall defect with herniation of few bowel loops,
      intestinal malrotation. Paralytic ileus and infections are the main causes of
      morbidity and mortality at neonatal age. In our case, in spite of the mild
      phenotype, prognosis has been complicated by the onset of functional bowel
      obstruction, caused by chemical peritonitis resulting from contact with either
      amniotic fluid and meconium. 

PMID- 25573644
TI  - Hyperammonemic coma in a patient with late-onset OTC deficiency.
AB  - Urea Cycle Disorders ( UCD ) are among the most common genetic diseases of the
      metabolism and ornithine transcarbamylase deficiency (OTC), an X-linked defect is
      the most frequent among them. It is responsible for hyperammonemia that can lead
      to chronic neurological illness and potentially to death in case of delayed
      diagnosis and treatment. With regards to the OTC deficiency there is great
      clinical heterogeneity with early-onset phenotypes with mostly poor prognosis and
      late-onset phenotypes with a better one. In the article it is reported the case
      of a 8 years old patient with diagnosis of OTC deficit with late-onset phenotype.
      The kid was brought to our hospital because of continuous vomiting and gastro-
      intestinal disorders, associated with irritability and lethargy later resulted
      into coma. Measurement of plasma ammonia concentration, followed by measurement
      of plasma amino acid and urine orotic acid levels allowed to diagnose the OTC
      deficit, lately confirmed by molecular genetic studies. The patient has been
      promptly treated with Sodium Phenylbutyrate, Arginine and discontinuing the
      protein intake. Gradually the ammonemia value decreased, and general and
      neurological conditions improved with resolution of the coma. To conclude, for
      patients presenting unexplained neurological symptoms, confusion and decreased
      level of consciousness, up to coma, urea cycle disorders and in particularly OTC
      deficiency should be considered in the differential diagnosis and an urgent
      ammonia level determined. In case of hyperammonemia, the treatment should be
      started immediately , even without a precise ethiologic diagnosis. 

PMID- 25573645
TI  - A case of spontaneous gastric rupture in a 5 years girl.
AB  - We describe a case of spontaneous gastric rupture in a child of 5 years old. The
      patient reached us in a serious condition; the anamnesis was negative for
      traumatic events or gastrointestinal disorders. An abdominal X-ray and CT scan
      revealed free air and fluid in the abdominal cavity, leading to the diagnosis of
      gastro-intestinal perforation. Submitted to urgent surgery, a rupture of the
      posterior wall of the stomach was found that was treated with gastrectomy "a la
      demande". The surgery follow-up was regular. Morphological and
      immunohistochemical study showed some muscular abnormalities of the muscular
      gastric wall. 

PMID- 25573646
TI  - Precocious puberty in a patient with Oculo-Auriculo-Verebral spectrum (OAVS).
AB  - The authors report on the first case of OAVS (Oculo-Auriculo- Vertebral
      Spectrum), with hemifacial microsomy, hydrocephalus, pubertas precox, thelarche
      at 4 years of age, vaginal bleeding at 5 years, and left ovary of adult type on
      echography (right ovary initially not visualized). FISH and CGH-ARRAYS methods
      were negative. By GnRH therapy the delay of onset puberty was obtained. The
      authors ascribe facial and ovary asymmetry to a derangement of blastogenesis,
      during which axial right-left structures begin the develop with consequent
      migration or interation with surrounding tissues of neural crest cells and
      alteration of diencephalic pituitary systems. 

PMID- 25573647
TI  - Spermine reverses lipopolysaccharide-induced memory deficit in mice.
AB  - BACKGROUND: Lipopolysaccharide (LPS) induces neuroinflammation and memory
      deficit. Since polyamines improve memory in various cognitive tasks, we
      hypothesized that spermine administration reverses LPS-induced memory deficits in
      an object recognition task in mice. The involvement of the polyamine binding site
      at the N-methyl-D-aspartate (NMDA) receptor and cytokine production in the
      promnesic effect of spermine were investigated. METHODS: Adult male mice were
      injected with LPS (250 MUg/kg, intraperitoneally) and spermine (0.3 to 1 mg/kg,
      intraperitoneally) or ifenprodil (0.3 to 10 mg/kg, intraperitoneally), or both,
      and their memory function was evaluated using a novel object recognition task. In
      addition, cortical and hippocampal cytokines levels were measured by ELISA four
      hours after LPS injection. RESULTS: Spermine increased but ifenprodil decreased
      the recognition index in the novel object recognition task. Spermine, at doses
      that did not alter memory (0.3 mg/kg, intraperitoneally), reversed the cognitive
      impairment induced by LPS. Ifenprodil (0.3 mg/kg, intraperitoneally) reversed the
      protective effect of spermine against LPS-induced memory deficits. However,
      spermine failed to reverse the LPS-induced increase of cortical and hippocampal
      cytokine levels. CONCLUSIONS: Spermine protects against LPS-induced memory
      deficits in mice by a mechanism that involves GluN2B receptors.

PMID- 25573648
TI  - PTSD, emotion dysregulation, and dissociative symptoms in a highly traumatized
      sample.
AB  - Exposure to multiple traumas has been shown to result in many negative mental
      health outcomes, including posttraumatic stress disorder (PTSD). Dissociation,
      which involves disruptions in memory, identity, and perceptions, may be a
      component of PTSD, particularly among individuals who have experienced childhood
      trauma. Emotion regulation difficulties are also strongly associated with
      childhood trauma and emotion dysregulation may be a particularly important factor
      to consider in the development and maintenance of dissociative symptoms. The goal
      of the present study was to determine whether emotion dysregulation mediated the
      relationship between PTSD symptoms and dissociation in a sample of 154 (80%
      female, 97% African-American) adults recruited from a public, urban hospital.
      PTSD was measured using the Clinician Administered PTSD Scale, emotion
      dysregulation was measured using the Difficulties in Emotion Regulation Scale,
      and dissociation was measured using the Multiscale Dissociation Inventory. A
      linear regression analysis showed that both PTSD and emotion dysregulation were
      statistically significant predictors of dissociation even after controlling for
      trauma exposure. Alexithymia and an inability to use emotion regulation
      strategies in particular were predictive of dissociation above and beyond other
      predictor variables. Using bootstrapping techniques, we found that overall
      emotion dyregulation partially mediated the effect of PTSD symptoms on
      dissociative symptoms. Our results suggest that emotion dysregulation may be
      important in understanding the relation between PTSD and dissociative symptoms.
      Treatment approaches may consider a focus on training in emotional understanding
      and the development of adaptive regulation strategies as a way to address
      dissociative symptoms in PTSD patients. 

PMID- 25573650
TI  - Erratum to: Efficacy of eribulin in women with metastatic breast cancer: a pooled
      analysis of two phase 3 studies.

PMID- 25573649
TI  - A comparative study of bronchoscopic microsample probe versus bronchoalveolar
      lavage in patients with burns-related inhalational injury, acute lung injury and
      chronic stable lung disease.
AB  - BACKGROUND AND OBJECTIVES: The bronchoscopic microsample (BMS) probe allows
      direct epithelial lining fluid (ELF) level measurement without saline lavage. We
      investigated whether cytokine levels in ELF from a BMS differed from those
      obtained by bronchoalveolar lavage (BAL) in stable and acute lung disease.
      METHODS: In a single-centre, prospective observational cohort study of 45
      patients, a sequential BMS probe procedure and BAL were performed on patients
      with stable chronic obstructive lung disease, interstitial lung disease, acute
      lung injury (ALI), burns-related inhalational injury or controls. ELF samples
      were assayed for IL-1beta, IL-6, IL-8, TNF-alpha and G-CSF. RESULTS: Both
      bronchoscopic microsampling and BAL showed significantly higher cytokine levels
      in the ELF from patients with ALI and burns-related inhalational injury than from
      those with chronic stable lung disease. The BMS method detected cytokine levels
      approximately 20- to 80-fold higher than the corresponding BAL (uncorrected for
      dilution). The ratio of BMS and BAL cytokine levels was as follows: the ratio for
      IL-1beta [mean 55, 95% confidence interval (CI) 34-88] was higher than that for
      IL-6 (mean 16, 95% CI 10-23, p = 0.015) and IL-8 (mean 13, 95% CI -5 to 36, p =
      0.03). The ratio for G-CSF (mean 43, 95% CI 24-75) was higher than that for IL-6
      (mean 16, 95% CI 10-23, p = 0.008). CONCLUSIONS: The BMS probe safely collects
      ELF with higher equivalent inflammatory cytokine concentrations than via BAL from
      patients with both acute and chronic lung disease and can be an alternative to
      saline BAL. Variations in cytokine concentrations between BMS and BAL and
      sampling-site differences warrant further study.

PMID- 25573652
TI  - Linkage disequilibrium and haplotype block structure in a composite beef cattle
      breed.
AB  - BACKGROUND: The development of linkage disequilibrium (LD) maps and the
      characterization of haplotype block structure at the population level are useful
      parameters for guiding genome wide association (GWA) studies, and for
      understanding the nature of non-linear association between phenotypes and genes.
      The elucidation of haplotype block structure can reduce the information of
      several single nucleotide polymorphisms (SNP) into the information of a haplotype
      block, reducing the number of SNPs in a coherent way for consideration in GWA and
      genomic selection studies. RESULTS: The maximum average LD, measured by r2 varied
      between 0.33 to 0.40 at a distance of < 2.5 kb, and the minimum average values of
      r2 varied between 0.05 to 0.07 at distances ranging from 400 to 500 kb, clearly
      showing that the average r2 reduced with the increase in SNP pair distances. The
      persistence of LD phase showed higher values at shorter genomic distances,
      decreasing with the increase in physical distance, varying from 0.96 at a
      distance of < 2.5 kb to 0.66 at a distance from 400 to 500 kb. A total of 78% of
      all SNPs were clustered into haplotype blocks, covering 1,57 Mb of the total
      autosomal genome size. CONCLUSIONS: This study presented the first high density
      linkage disequilibrium map and haplotype block structure for a composite beef
      cattle population, and indicates that the high density SNP panel over 700 k can
      be used for genomic selection implementation and GWA studies for Canchim beef
      cattle.

PMID- 25573651
TI  - Glycyrrhetinic acid induces G1-phase cell cycle arrest in human non-small cell
      lung cancer cells through endoplasmic reticulum stress pathway.
AB  - Glycyrrhetinic acid (GA) is a natural compound extracted from liquorice, which is
      often used in traditional Chinese medicine. The purpose of the present study was
      to investigate the antitumor effect of GA in human non-small cell lung cancer
      (NSCLC), and its underlying mechanisms in vitro. We have shown that GA suppressed
      the proliferation of A549 and NCI-H460 cells. Flow cytometric analysis showed
      that GA arrested cell cycle in G0/G1 phase without inducing apoptosis. Western
      blot analysis indicated that GA mediated G1-phase cell cycle arrest by
      upregulation of cyclin-dependent kinase inhibitors (CKIs) (p18, p16, p27 and p21)
      and inhibition of cyclins (cyclin-D1, -D3 and -E) and cyclin-dependent kinases
      (CDKs) (CDK4, 6 and 2). GA also maintained pRb phosphorylation status, and
      inhibited E2F transcription factor 1 (E2F-1) in both cell lines. GA upregulated
      the unfolded proteins, Bip, PERK and ERP72. Accumulation of unfolded proteins in
      the endoplasmic reticulum (ER) triggered the unfolded protein response (UPR),
      which could be the mechanism by which GA inhibited cell proliferation in NSCLC
      cells. GA then coordinated the induction of ER chaperones, which decreased
      protein synthesis and induced cell cycle arrest in the G1 phase. This study
      provides experimental evidence to support the development of GA as a
      chemotherapeutic agent for NSCLC.

PMID- 25573654
TI  - Vitamin D supplementation and health-related quality of life: a systematic review
      of the literature.
AB  - Vitamin D deficiency and insufficiency are highly prevalent worldwide and thought
      to potentiate a variety of chronic disease states, including diabetes, cancer,
      and depression. Routine vitamin D supplementation is often needed to meet vitamin
      D requirements. Little is known regarding the effect of vitamin D supplementation
      on quality of life. The purpose of this article was to systematically review the
      literature regarding quality-of-life outcomes from vitamin D supplementation in
      healthy and clinical populations. Clinical trials of vitamin D supplementation,
      where quality-of-life outcomes were reported, were selected from Medline and Web
      of Science databases. Inclusion criteria were English language articles available
      online (published between 1950 and May 2014), primary research articles, studies
      conducted on human beings, and treatment/supplementation with vitamin D. Articles
      were excluded if they involved topical vitamin D application or implicit
      cotreatment with other vitamins (eg, multivitamins). Articles selected for review
      were examined for process and methodologic quality using validated methodologies.
      A total of 15 articles met the inclusion criteria for review. Interventions were
      highly variable in terms of study population (eg, healthy/diseased,
      children/elderly, and baseline vitamin D status) vitamin D dose, and duration of
      follow-up. Vitamin D supplementation ranged from 400 IU/day for an average of 7.1
      years, to a single 300, 000 IU dose. The main tools used to capture quality of
      life were adaptations of validated, questionnaires (Medical Outcomes Study Short
      Form 36-item questionnaire and EuroQOL five dimension questionnaire). Vitamin D
      supplementation was not associated with significant changes in quality of life.
      Studies that reported changes in quality of life as a result of vitamin D
      supplementation were in clinical populations on short-term vitamin D. Most
      articles reviewed displayed poor methodologic quality (eg, no
      randomization/blinding, dropout description, or vitamin D assessment). Current
      evidence indicates that vitamin D supplementation may have a small to moderate
      effect on quality of life when used on a short-term basis in diseased
      populations. However, the evidence for a beneficial effect of long-term vitamin D
      supplementation on health-related quality of life is lacking. 

PMID- 25573657
TI  - Sounding the warning on the potential for oesophageal injury resulting from use
      of the nMARQTM for ablation of atrial fibrillation.

PMID- 25573656
TI  - A stepwise electrocardiographic algorithm for differentiation of mid-septal vs.
      apical right ventricular lead positioning: the SPICE ECG substudy.
AB  - AIMS: Right ventricular (RV) septum is a non-apical site targeted during lead
      implantation. Electrocardiographic (ECG) recognition of mid-septal lead location
      is challenging. The aim of the study is to determine ECG correlates of RV mid
      septal pacing. METHODS AND RESULTS: The present study is a pre-specified analysis
      of a prospective, multicenter study, which randomized recipients of an
      implantable cardioverter defibrillator to an apical vs. mid-septal RV lead
      positioning. Following implantation, a 12-lead ECG was recorded during intrinsic
      rhythm and RV pacing. In total, 227 patients, 121 in the apical group (76.9%
      males, 67.1 +/- 11.3 years) and 106 in the mid-septal group (82.1% males, age
      64.7 +/- 12.7 years) were included. Apically as compared with septally paced
      patients had significantly longer paced QRS duration (177.0 +/- 25.0 vs. 170.4 +/
      21.7, respectively, P = 0.03) and significantly more leftward paced QRS axis (
      71.6 +/- 33.3 degrees  vs. 9.4 +/- 86.5 degrees , respectively, P < 0.001). A
      significantly higher proportion of patients in the mid-septal as compared with
      the apical group displayed predominantly positive QRS in lead V6 (62.3 vs. 4.1%,
      P < 0.001), predominantly positive QRS in any of the inferior leads (53.8 vs.
      4.1%, P < 0.001), and a QR pattern in lead aVL (53.3 vs. 3.3%, P < 0.001). These
      ECG correlates were incorporated in a stepwise algorithm with total sensitivity
      of 87% and specificity of 90% for the identification of a mid-septal lead
      location. CONCLUSION: A mid-septal lead location may be identified using a simple
      stepwise algorithm, based on the presence of positive QRS in lead V6, positive
      QRS in any of the inferior leads, and a QR pattern in lead aVL.

PMID- 25573658
TI  - Strategies to reduce infections during the cardiac implantable electronic device
      implant: a time to name and shame.

PMID- 25573660
TI  - Precise measurement of long-range heteronuclear coupling constants by a novel
      broadband proton-proton-decoupled CPMG-HSQMBC method.
AB  - A broadband proton-proton-decoupled CPMG-HSQMBC method for the precise and direct
      measurement of long-range heteronuclear coupling constants is presented. The
      Zangger-Sterk-based homodecoupling scheme reported herein efficiently removes
      unwanted proton-proton splittings from the heteronuclear multiplets, so that the
      desired heteronuclear couplings can be determined simply by measuring frequency
      differences between singlet maxima in the resulting spectra. The proposed pseudo
      1D/2D pulse sequences were tested on nucleotides, a metal complex incorporating P
      heterocycles, and diglycosyl (di)selenides, as well as on other carbohydrate
      derivatives, for the extraction of (n) J((1) H,(31) P), (n) J((1) H,(77) Se), and
      (n) J((1) H,(13) C) values, respectively. 

PMID- 25573662
TI  - Nickel-catalyzed monoarylation of ammonia.
AB  - Structurally diverse (hetero)aryl chloride, bromide, and tosylate electrophiles
      were employed in the Ni-catalyzed monoarylation of ammonia, including
      chemoselective transformations. The employed JosiPhos/[Ni(cod)2] catalyst system
      enables the use of commercially available stock solutions of ammonia, or the use
      of ammonia gas in these reactions, thereby demonstrating the versatility and
      potential scalability of the reported protocol. Proof-of-principle experiments
      established that air-stable [(JosiPhos)NiCl2] precatalysts can be employed
      successfully in such transformations.

PMID- 25573663
TI  - Esophageal fistula complicating thyroid lobectomy.
AB  - Thyroidectomy is associated with low morbidity and mortality. Esophageal
      perforation following thyroidectomy has been reported only three times
      previously, with subsequent fistulization occurring in two of these cases. The
      authors present the first such case report in the English-speaking literature. 

PMID- 25573664
TI  - Synthesis of imidazoles via cascade reaction of nitroallylic acetates with
      amidines and studies on their trypanocidal activity.
AB  - A one-pot, two step synthesis of highly substituted imidazoles has been carried
      out in good to excellent yields for the first time via a cascade intermolecular
      aza-SN2'-intramolecular aza-Michael addition involving a variety of Morita-Baylis
      Hillman acetates of nitroalkenes and amidines in the presence of DABCO at room
      temperature. The synthetic and biological utility of the products has been
      demonstrated. In particular, some of the imidazoles exhibited potent activity
      against T. cruzi, the etiological agent of Chagas disease. 

PMID- 25573661
TI  - Advances in biology and mechanics of rotator cuff repair.
AB  - High initial fixation strength, mechanical stability and biological healing of
      the tendon-to-bone interface are the main goals after rotator cuff repair
      surgery. Advances in the understanding of rotator cuff biology and biomechanics
      as well as improvements in surgical techniques have led to the development of new
      strategies that may allow a tendon-to-bone interface healing process, rather than
      the formation of a fibrovascular scar tissue. Although single-row repair remains
      the most cost-effective technique to address a rotator cuff tear, some biological
      intervention has been recently introduced to improve tissue healing and clinical
      outcome of rotator cuff repair. Animal models are critical to ensure safety and
      efficacy of new treatment strategies; however, although rat shoulders as well as
      sheep and goats are considered the most appropriate models for studying rotator
      cuff pathology, no one of them can fully reproduce the human condition. Emerging
      therapies involve growth factors, stem cells and tissue engineering. Experimental
      application of growth factors and platelet-rich plasma demonstrated promising
      results, but has not yet been transferred into standardized clinical practice.
      Although preclinical animal studies showed promising results on the efficacy of
      enhanced biological approaches, application of these techniques in human rotator
      cuff repairs is still very limited. Randomized controlled clinical trials and
      post-marketing surveillance are needed to clearly prove the clinical efficacy and
      define proper indications for the use of combined biological approaches. The
      following review article outlines the state of the art of rotator cuff repair and
      the use of growth factors, scaffolds and stem cells therapy, providing future
      directions to improve tendon healing after rotator cuff repair. LEVEL OF
      EVIDENCE: Expert opinion, Level V.

PMID- 25573666
TI  - Assembling different antennas of the gp120 high mannose-type glycans on gold
      nanoparticles provides superior binding to the anti-HIV antibody 2G12 than the
      individual antennas.
AB  - In order to re-build Man9GlcNAc2 clusters of the HIV gp120 glycoprotein, ~2 nm
      gold glyconanoparticles (GNPs) were coated with the synthetic partial structures
      of Man9, the tetramannoside Manalpha1-2Manalpha1-2Manalpha1-3Manalpha1- and the
      pentamannoside Manalpha1-2Manalpha1-3[Manalpha1-2Manalpha1-6]Manalpha1-. Their
      interactions with the anti-HIV broadly neutralizing antibody 2G12 were studied by
      surface plasmon resonance (SPR)-based biosensors and saturation transfer
      difference (STD)-NMR spectroscopy. A synergistic effect of the tetra- and
      pentamannosides multimerized on a same GNP was observed. The assembly of these
      antennas of the gp120 high-mannose type glycan on GNPs provided superior binding
      to the anti-HIV antibody 2G12 with respect to GNPs carrying only the individual
      oligomannosides. The results presented in this work provide new molecular
      information on the interactions between clusters of oligomannosides and 2G12 that
      could help in the design of a carbohydrate-based vaccine against HIV.

PMID- 25573667
TI  - The role of stents in the palliation of oesophageal cancer.
AB  - Oesophageal cancer is the 13th most common cancer in the UK and very few patients
      are suitable for radical treatment. Almost all of the remaining patients suitable
      for palliative treatment only have some degree of dysphagia requiring treatment.
      Self-expanding metal stents are currently the most common means of improving
      swallowing. This review discusses when we should stent patients, what type of
      stent we should use and how it can be carried out as well as illustrating the
      problems that can occur immediately after stent insertion and longer term
      problems. 

PMID- 25573665
TI  - PPARgamma deficiency results in severe, accelerated osteoarthritis associated
      with aberrant mTOR signalling in the articular cartilage.
AB  - OBJECTIVES: We have previously shown that peroxisome proliferator-activated
      receptor gamma (PPARgamma), a transcription factor, is essential for the normal
      growth and development of cartilage. In the present study, we created inducible
      cartilage-specific PPARgamma knockout (KO) mice and subjected these mice to the
      destabilisation of medial meniscus (DMM) model of osteoarthritis (OA) to
      elucidate the specific in vivo role of PPARgamma in OA pathophysiology. We
      further investigated the downstream PPARgamma signalling pathway responsible for
      maintaining cartilage homeostasis. METHODS: Inducible cartilage-specific
      PPARgamma KO mice were generated and subjected to DMM model of OA. We also
      created inducible cartilage-specific PPARgamma/mammalian target for rapamycin
      (mTOR) double KO mice to dissect the PPARgamma signalling pathway in OA. RESULTS:
      Compared with control mice, PPARgamma KO mice exhibit accelerated OA phenotype
      with increased cartilage degradation, chondrocyte apoptosis, and the
      overproduction of OA inflammatory/catabolic factors associated with the increased
      expression of mTOR and the suppression of key autophagy markers. In vitro rescue
      experiments using PPARgamma expression vector reduced mTOR expression, increased
      expression of autophagy markers and reduced the expression of OA
      inflammatory/catabolic factors, thus reversing the phenotype of PPARgamma KO mice
      chondrocytes. To dissect the in vivo role of mTOR pathway in PPARgamma
      signalling, we created and subjected PPARgamma-mTOR double KO mice to the OA
      model to see if the genetic deletion of mTOR in PPARgamma KO mice (double KO) can
      rescue the accelerated OA phenotype observed in PPARgamma KO mice. Indeed,
      PPARgamma-mTOR double KO mice exhibit significant protection/reversal from OA
      phenotype. SIGNIFICANCE: PPARgamma maintains articular cartilage homeostasis, in
      part, by regulating mTOR pathway.

PMID- 25573668
TI  - Treatment approaches of palliative medicine specialists for depression in the
      palliative care setting: findings from a qualitative, in-depth interview study.
AB  - BACKGROUND: Treatment of depression in the palliative care setting is complicated
      by varied treatment preferences, a small body of research, and unique challenges
      associated with the end-of-life. Little is known about the treatment practices of
      medical practitioners in this setting. OBJECTIVE: This study aimed to investigate
      and characterise the treatment approaches of palliative medicine specialists for
      depression. DESIGN: Semistructured, in-depth interviews were conducted to explore
      explanatory models of depression from palliative medicine specialists, including
      a focus on treatment. Verbatim interview transcripts were analysed for themes.
      SETTING/PARTICIPANTS: Palliative medicine specialists practising in Australia
      were recruited and purposively sampled. Nine participants were interviewed to
      reach data saturation. RESULTS: Five themes were identified in relation to
      treatment of depression: (1) guiding principles of treatment; (2) treatment
      approaches; (3) factors underpinning treatment decisions; (4) difficulties
      arising in treatment; and (5) interdisciplinary roles. Participants described
      five distinct treatment approaches, consisting of biological orientation,
      psychosocial orientation, combination approach, undifferentiated approach and
      ambivalence. Treatment decisions were contingent on patient, depression,
      clinician and sociocultural factors. Difficulties included discomfort with
      treating depression, being inadequately equipped and confronting therapeutic
      limitations. Treating depression was considered to require multidisciplinary team
      effort. CONCLUSIONS: Palliative medicine specialists' treatment approaches are
      linked to their concepts of and causal explanations for depression. Future
      treatment guidelines could aim to consider specific varieties of depression, be
      more differentiated in treatment modality and type, and consider decision-shaping
      factors. Continuing mental health education and the incorporation of psychiatry
      and psychology into palliative care services may have enduring benefits.

PMID- 25573655
TI  - Partial Meal Replacement Plan and Quality of the Diet at 1 Year: Action for
      Health in Diabetes (Look AHEAD) Trial.
AB  - BACKGROUND: Little is known about diet quality with a reduced-energy, low-fat,
      partial meal replacement plan, especially in individuals with type 2 diabetes.
      The Action for Health in Diabetes (Look AHEAD) trial implemented a partial meal
      replacement plan in the Intensive Lifestyle Intervention. OBJECTIVE: To compare
      dietary intake and percent meeting fat-related and food group dietary
      recommendations in Intensive Lifestyle Intervention and Diabetes Support and
      Education groups at 12 months. DESIGN: A randomized controlled trial comparing
      Intensive Lifestyle Intervention with Diabetes Support and Education at 0 and 12
      months. PARTICIPANTS/SETTING: From 16 US sites, the first 50% of participants
      (aged 45 to 76 years, overweight or obese, with type 2 diabetes) were invited to
      complete dietary assessments. Complete 0- and 12-month dietary assessments
      (collected between 2001 and 2004) were available for 2,397 participants (46.6% of
      total participants), with 1,186 randomized to Diabetes Support and Education
      group and 1,211 randomized to Intensive Lifestyle Intervention group. MAIN
      OUTCOME MEASURES: A food frequency questionnaire assessed intake: energy; percent
      energy from protein, fat, carbohydrate, polyunsaturated fatty acids, and
      saturated fats; trans-fatty acids; cholesterol; fiber; weekly meal replacements;
      and daily servings from food groups from the Food Guide Pyramid. STATISTICAL
      ANALYSES PERFORMED: Mixed-factor analyses of covariance, using Proc MIXED with a
      repeated statement, with age, sex, race/ethnicity, education, and income
      controlled. Unadjusted chi2 tests compared percent meeting fat-related and food
      group recommendations at 12 months. RESULTS: At 12 months, Intensive Lifestyle
      Intervention participants had a significantly lower fat and cholesterol intake
      and greater fiber intake than Diabetes Support and Education participants.
      Intensive Lifestyle Intervention participants consumed more servings per day of
      fruits; vegetables; and milk, yogurt, and cheese; and fewer servings per day of
      fats, oils, and sweets than Diabetes Support and Education participants. A
      greater percentage of Intensive Lifestyle Intervention participants than Diabetes
      Support and Education participants met fat-related and most food group
      recommendations. Within Intensive Lifestyle Intervention, a greater percentage of
      participants consuming two or more meal replacements per day than participants
      consuming less than one meal replacement per day met most fat-related and food
      group recommendations. CONCLUSIONS: The partial meal replacement plan consumed by
      Intensive Lifestyle Intervention participants was related to superior diet
      quality.

PMID- 25573669
TI  - Multivariate detrending of fMRI signal drifts for real-time multiclass pattern
      classification.
AB  - Signal drift in functional magnetic resonance imaging (fMRI) is an unavoidable
      artifact that limits classification performance in multi-voxel pattern analysis
      of fMRI. As conventional methods to reduce signal drift, global demeaning or
      proportional scaling disregards regional variations of drift, whereas voxel-wise
      univariate detrending is too sensitive to noisy fluctuations. To overcome these
      drawbacks, we propose a multivariate real-time detrending method for multiclass
      classification that involves spatial demeaning at each scan and the recursive
      detrending of drifts in the classifier outputs driven by a multiclass linear
      support vector machine. Experiments using binary and multiclass data showed that
      the linear trend estimation of the classifier output drift for each class (a
      weighted sum of drifts in the class-specific voxels) was more robust against
      voxel-wise artifacts that lead to inconsistent spatial patterns and the effect of
      online processing than voxel-wise detrending. The classification performance of
      the proposed method was significantly better, especially for multiclass data,
      than that of voxel-wise linear detrending, global demeaning, and classifier
      output detrending without demeaning. We concluded that the multivariate approach
      using classifier output detrending of fMRI signals with spatial demeaning
      preserves spatial patterns, is less sensitive than conventional methods to sample
      size, and increases classification performance, which is a useful feature for
      real-time fMRI classification. 

PMID- 25573671
TI  - The complexity of consenting to clinical research in phase I pediatric cancer
      studies.
AB  - The principal aim of phase I studies is to define the recommended dosing of drugs
      for phase II studies through assessment of drug pharmacokinetics and observation
      of the drug's toxicity profile. In the setting of pediatric oncology, the use of
      an experimental drug in phase I study is offered when prognosis is poor. Thus,
      phase I oncology studies are not given to patients with a primary purpose of an
      intent to cure. They may offer little to no treatment benefit and carry a
      potential toxic effect. They may offer other benefits such as improved quality of
      life and relief of pain, however. Three parties are involved in the informed
      consent process: the parents, patients, and physicians. Families report hope as
      the main cause for enrollment. Physicians focus on providing information so
      families can decide about participation. Physicians also try to maintain hope
      despite understanding the nature of the disease. This makes the informed consent
      complicated for all parties involved in the process. The purpose of this review
      is to discuss the aims of phase I studies in pediatric oncology and to convey the
      ethical challenges that patients, parents, and physicians are facing when
      discussing informed consent with potential study participants. 

PMID- 25573670
TI  - Arbitration between controlled and impulsive choices.
AB  - The impulse to act for immediate reward often conflicts with more deliberate
      evaluations that support long-term benefit. The neural architecture that
      negotiates this conflict remains unclear. One account proposes a single neural
      circuit that evaluates both immediate and delayed outcomes, while another
      outlines separate impulsive and patient systems that compete for behavioral
      control. Here we designed a task in which a complex payout structure divorces the
      immediate value of acting from the overall long-term value, within the same
      outcome modality. Using model-based fMRI in humans, we demonstrate separate
      neural representations of immediate and long-term values, with the former tracked
      in the anterior caudate (AC) and the latter in the ventromedial prefrontal cortex
      (vmPFC). Crucially, when subjects' choices were compatible with long-run
      consequences, value signals in AC were down-weighted and those in vmPFC were
      enhanced, while the opposite occurred when choice was impulsive. Thus, our data
      implicate a trade-off in value representation between AC and vmPFC as underlying
      controlled versus impulsive choice. 

PMID- 25573672
TI  - An analysis of the association between a polymorphism of KCNJ11 and diabetic
      retinopathy in a Chinese Han population.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have reported that the
      polymorphism rs5219 of the potassium inwardly rectifying channel, subfamily J,
      member 11 (KCNJ11) is associated with type 2 diabetes mellitus (T2DM). Given that
      diabetic retinopathy (DR) is one of the most common microvascular complications
      of T2DM, GWAS have identified a number of potential susceptibility genes for DR.
      However, only a fraction of them have been replicated in different studies and
      show consistent genetic associations with the occurrence of DR. The aim of the
      present study was to investigate whether common variants of KCNJ11 confer DR in a
      cohort of the Chinese Han population. METHODS: A case-control study of 580 T2DM
      patients, including 105 T2DM with DR and 475 T2DM without DR was performed. A
      single nucleotide polymorphism (SNP) of KCNJ11 (rs5219) was genotyped, and its
      association with DR was explored using a dominant genetic model. Genotyping was
      performed by iPLEX technology. Univariate and multivariate logistic regression
      (MLR) analysis controlling for confounders was conducted to evaluate the
      association between rs5219 and DR. RESULTS: The A allele frequency of rs5219 was
      significantly higher in DR patients than that in the patients without DR (49.01%
      versus 38.68%, P <0.05). We found the minor A allele could increase the risk to
      develop DR (ORint = 1.58, 95% CI: 1.139 to 2.192 for allele and P = 0.006, ORint
      =1.607, 95% CI: 1.267 to 2.038 for genotype and P <0.001) in the Chinese Han
      population. CONCLUSIONS: Our findings provided evidence that KCNJ11 was
      associated with DR in Chinese Han patients with T2DM.

PMID- 25573674
TI  - New perspectives in Clostridium difficile disease pathogenesis.
AB  - Clostridium difficile is associated with a spectrum of clinical manifestations
      ranging from asymptomatic carriage to severe life-threatening pseudomembranous
      colitis. Current perspectives indicate that C difficile pathogenesis is a
      multifactorial disease process dictated by pathogenic toxin production, gut
      microbial dysbiosis, and altered host inflammatory responses. This article
      summarizes recent findings underpinning the cellular and molecular mechanisms
      regulating bacterial virulence and sheds new light on the critical roles of the
      host immune response, intestinal microbiota, and metabolome in mediating disease
      pathogenesis. 

PMID- 25573676
TI  - Treatment of Clostridium difficile infections.
AB  - Vancomycin and metronidazole were historically considered equivalent therapies
      for the management of Clostridium difficile infections (CDI); however, recent
      data confirm more favorable outcomes with vancomycin. Fidaxomicin is a narrow
      spectrum antibiotic that has an advantage in reducing recurrence rates compared
      with vancomycin, possibly owing to its sparing effect on normal colonic
      microbiota. Data are limited for guiding management of CDI recurrences,
      particularly multiple recurrences. Several empiric approaches to manage these
      cases are reviewed. 

PMID- 25573673
TI  - Distinct p21 requirements for regulating normal and self-reactive T cells through
      IFN-gamma production.
AB  - Self/non-self discrimination characterizes immunity and allows responses against
      pathogens but not self-antigens. Understanding the principles that govern this
      process is essential for designing autoimmunity treatments. p21 is thought to
      attenuate autoreactivity by limiting T cell expansion. Here, we provide direct
      evidence for a p21 role in controlling autoimmune T cell autoreactivity without
      affecting normal T cell responses. We studied C57BL/6, C57BL/6/lpr and MRL/lpr
      mice overexpressing p21 in T cells, and showed reduced autoreactivity and
      lymphadenopathy in C57BL/6/lpr, and reduced mortality in MRL/lpr mice. p21
      inhibited effector/memory CD4(+) CD8(+) and CD4(-)CD8(-) lpr T cell accumulation
      without altering defective lpr apoptosis. This was mediated by a previously non
      described p21 function in limiting T cell overactivation and overproduction of
      IFN-gamma, a key lupus cytokine. p21 did not affect normal T cell responses,
      revealing differential p21 requirements for autoreactive and normal T cell
      activity regulation. The underlying concept of these findings suggests potential
      treatments for lupus and autoimmune lymphoproliferative syndrome, without
      compromising normal immunity. 

PMID- 25573675
TI  - Environmental interventions to control Clostridium difficile.
AB  - The control of Clostridium difficile infection is paramount. C difficile spores
      are difficult to eradicate and can survive on surfaces for prolonged periods of
      time. Hand washing with either plain or antimicrobial soap is effective in
      removing C difficile spores from hands. Patients should be placed in private
      rooms and under contact precautions to prevent transmission to other patients.
      Regular hospital germicides are not sporicidal and hypochlorite solutions are
      required for surface disinfection. In outbreak situations, a multifaceted
      approach is required. 

PMID- 25573677
TI  - Malpractice in treatment of sinonasal disease by otolaryngologists: a review of
      the past 10 years.
AB  - OBJECTIVE: Sinonasal disease is a common condition treated by otolaryngologists.
      Malpractice in this area is the most common litigation faced by
      otolaryngologists. This study analyzes malpractice in the treatment of sinonasal
      disease. STUDY DESIGN: Case series, review of legal records. SETTING: Legal
      databases. SUBJECTS AND METHODS: Using 2 different computerized legal databases,
      the phrase medical malpractice was searched with terms related to sinonasal
      disease involving court cases in the past 10 years (2004-2013), yielding 26
      cases. The cases were analyzed for pertinent data regarding plaintiffs,
      presenting complaint, practice setting, type of malpractice, resulting injury,
      result of verdict, and amount of reward or settlement. RESULTS: Chronic sinusitis
      (42%) was the most common presenting symptom. Many cases included multiple types
      of alleged malpractice, with the most common being negligent technique (38%) and
      lack of informed consent (27%). The most common alleged injuries included
      cerebrospinal fluid leak, meningitis, nasal obstruction, and orbital trauma.
      Defendants prevailed in 13 of 18 cases in which outcomes were known, with mean
      award of $225,000 and mean settlement of $212,500. The cases won by plaintiffs
      were all in a private practice setting. CONCLUSION: Otolaryngologists should be
      aware of the causes of malpractice litigation as it relates to treatment of
      sinonasal disease. Lack of informed consent continues to be a common allegation,
      and surgeons should ensure complete informed consent is obtained and well
      documented. A unified and complete database of medical malpractice cases is
      needed to allow for further analysis of specialty-related claims.

PMID- 25573678
TI  - Consistent ipsilateral development of the posterior extension of the quadrangular
      cartilage and bony spur formation in nasal septal deviation.
AB  - OBJECTIVE: Septal spurs are exceedingly common structural deformities that
      contribute to nasal obstruction and often require surgical correction. The
      posterior extension of the quadrangular cartilage (PEQC) and its relationship
      with septal spurs have not been previously examined. We seek to examine the
      anatomic and histologic relationship of the PEQC and concurrent septal spurs in
      patients undergoing septoplasty. STUDY DESIGN: Prospective cohort study. SETTING:
      Facial plastic and rhinology center in tertiary hospital setting. SUBJECT AND
      METHODS: Thirty patients with septal deviation are described in this series. The
      quadrangular cartilage and associated septal spur were removed en bloc from
      patients undergoing septoplasty. The length of the PEQC, the side of spur
      deviation, and the relationship of the PEQC to the spur (ipsilateral vs
      contralateral) were recorded. RESULTS: The mean length of the PEQC, beyond the
      bony-cartilaginous junction, was 30.06+/-6.06 mm. The PEQC was present on the
      ipsilateral side of the spur deviation in all 30 patients (100%). CONCLUSION: At
      sites of septal spur formation, the quadrangular cartilage possesses an average 3
      cm extension beyond its junction with the bony components of the septum. This
      cartilaginous extension is exclusively found on the same side of spur deviation.
      These findings have implications on our understanding of the ontogeny of commonly
      found septal spurs and deviations, as well as treatment strategies and cartilage
      graft harvesting.

PMID- 25573679
TI  - Psychosocial distress in patients with thyroid cancer.
AB  - OBJECTIVE: The purpose of this study is to evaluate levels of psychosocial
      distress in thyroid cancer patients. An analysis of factors contributing to
      levels of distress is included. STUDY DESIGN: Individual retrospective cohort
      study. SETTING: Head and neck cancer clinic at the Huntsman Cancer Institute.
      SUBJECTS AND METHODS: A total of 118 newly diagnosed thyroid cancer patients were
      included in the study. Univariate and multivariate analyses evaluated levels of
      and factors contributing to distress. RESULTS: Almost half (43.3%) of patients
      had significant distress. Those with self-reported psychiatric history, use of
      antidepressant medication, and history of radiation treatment had higher levels
      of distress. On multivariate analysis, patient endorsement of emotional issues
      predicted a higher distress level. CONCLUSIONS: Thyroid cancer patients have high
      distress levels. Identification of thyroid cancer patients with high distress
      levels is important to offer additional support during cancer therapy.

PMID- 25573680
TI  - Early versus delayed endoscopic sinus surgery in patients with chronic
      rhinosinusitis: impact on health care utilization.
AB  - OBJECTIVE: To evaluate the impact of early versus delayed endoscopic sinus
      surgery (ESS) in terms of postoperative health care utilization, using a patient
      cohort with chronic rhinosinusitis (CRS). STUDY DESIGN: Retrospective
      administrative database analysis. SETTING: US-based primary and secondary sites
      of care. SUBJECTS AND METHODS: CRS patients with ESS in 2010-with no other ESS
      before 2010 and with complete medical history from 2004 to 2012-were identified
      within the MarketScan database. Patients were characterized by time interval of
      first sinusitis or nasal polyposis diagnosis to ESS and grouped as following:
      group 1, <1 year (n=818); group 2, 1 to <2 years (n=247); group 3, 2 to <3 years
      (n=274); group 4, 3 to <4 years (n=364); group 5, 4 to <5 years (n=595); and
      group 6, >=5 years (n=535). Outpatient visits/procedures and prescriptions
      associated with sinusitis and/or nasal polyps were analyzed for 1 year
      preoperatively and 2 years postoperatively. Subanalyses were conducted on
      separate cohorts with or without asthma or polyps, within each group. RESULTS:
      Patients in group 1 had significantly fewer visits and prescriptions than
      patients in group 6 (postoperative visits: group 1, 4.45 [95% CI, 4.06-4.84];
      group 6, 6.70 [95% CI, 6.10-7.30; prescriptions: group 1, 4.54 [95% CI, 4.12
      4.96]; group 6, 7.61 [95% CI, 6.92-8.31]). Gradual increases in utilization were
      observed from groups 1 to 6. Subanalysis of patients with and without asthma or
      polyps showed similar findings. CONCLUSION: Early intervention after diagnoses of
      CRS, with or without asthma or polyps, is associated with lower health care
      utilization than intervention after many years of medical management.

PMID- 25573681
TI  - Cytologic and functional alterations of nasal mucosa in smokers: temporary or
      permanent damage?
AB  - OBJECTIVE: Tobacco smoke is a significant risk factor for respiratory diseases.
      The purpose of this study is to analyze the cytologic and functional features of
      nasal mucosa in smokers, nonsmokers, and ex-smokers to evaluate if nasal
      alterations in smokers are permanent or reversible conditions after smoking
      cessation. STUDY DESIGN: Case series with planned data collection. SETTING:
      University medical center. SUBJECTS AND METHODS: Ninety healthy volunteers
      recruited from the staff of Alfredo Fiorini Hospital, Sapienza University of
      Rome, were enrolled in this prospective study from October to November 2013. We
      divided the cases according to smoking habits (smokers, nonsmokers, ex-smokers).
      Each group was composed of 30 subjects. Cytologic features of nasal mucosa and
      effectiveness of nasal mucociliary clearance were studied, focusing on 4
      parameters: (1) nasal mucociliary clearance, assessed by saccharin nasal transit
      time; (2) ratio between the number of ciliated cells and goblet cells, analyzed
      by microscopic observation of cytologic specimens of nasal mucosa that had
      undergone May Grunwald Giemsa staining; (3) evaluation of ciliary motility; and
      (4) time of ciliary movement of ciliated cells analyzed by phase-contrast
      microscopy. RESULTS: All parameters were significantly reduced in the smokers
      compared to the nonsmokers. There were no statistically significant differences
      between the nonsmoker and ex-smoker groups. CONCLUSION: Cigarette smoking causes
      cytologic modifications of nasal mucosa that influence the effectiveness of
      mucociliary clearance. Our preliminary study suggests that these changes are not
      permanent and that nasal mucosa of ex-smokers recovers normal cytologic and
      functional features.

PMID- 25573682
TI  - A case of multiple neurofibroma/schwannoma hybrid tumors of the facial nerve.

PMID- 25573683
TI  - Comparison of hybrid laryngotracheal reconstruction to traditional single- and
      double-stage laryngotracheal reconstruction.
AB  - OBJECTIVES: (1) To describe outcomes from and modifications to the hybrid
      laryngotracheal reconstruction (LTR) technique and (2) to compare this technique
      to traditional single- and double-stage LTR (ssLTR/dsLTR). STUDY DESIGN: Chart
      review with case series. SETTING: Tertiary care otolaryngology specialty
      hospital. SUBJECTS: All patients under 18 years of age who underwent LTR by a
      single surgeon from July 1, 2009, to December 31, 2013. METHODS: Charts were
      assessed for age, gender, etiology of stenosis, type of reconstruction,
      comorbidities, length of stay, complications, and tracheostomy status. Analysis
      was performed using Kruskal-Wallis and Wilcoxon rank sum analysis. RESULTS: Forty
      four patients were identified, with 13 hybrid LTRs, 27 ssLTRs, and 4 dsLTRs. Of
      the hybrid LTRs, an overall decannulation rate of 76.9% was noted, comparable to
      those for dsLTR. The hybrid LTR technique offered a significantly shorter period
      of narcotic use when compared to ssLTR (median 15 vs 21 days, P<.01). No patients
      in the hybrid LTR group developed supraglottic granulation tissue. There was no
      statistically significant difference in median length of stay for ssLTRs, dsLTRs,
      and hybrid LTRs (P=.38). CONCLUSION: The hybrid LTR technique is well tolerated
      and useful in patients of all ages. Narcotics can be weaned more quickly due to
      the presence of a secure airway at all times via the existing tracheostomy. Use
      of a long stent prevents formation of granulation tissue that may be seen with a
      suprastomal stent. This technique should be considered in patients with high
      grade stenosis with a preexisting tracheostomy.

PMID- 25573684
TI  - PIAS3 expression in squamous cell lung cancer is low and predicts overall
      survival.
AB  - Unlike lung adenocarcinoma, little progress has been made in the treatment of
      squamous cell lung carcinoma (SCC). The Cancer Genome Atlas (TCGA) has recently
      reported that receptor tyrosine kinase signaling pathways are altered in 26% of
      SCC tumors, validating the importance of downstream Signal Transducers and
      Activators of Transcription 3 (STAT3) activity as a prime therapeutic target in
      this cancer. In the present report we examine the status of an endogenous
      inhibitor of STAT3, called Protein Inhibitor of Activated STAT3 (PIAS3), in SCC
      and its potential role in this disease. We examine PIAS3 expression in SCC tumors
      and cell lines by immunohistochemistry of a tissue microarray and western
      blotting. PIAS3 mRNA expression and survival data are analyzed in the TCGA data
      set. SCC cell lines are treated with curcumin to regulate PIAS3 expression and
      cell growth. PIAS3 protein expression is decreased in a majority of lung SCC
      tumors and cell lines. Analysis of PIAS3 mRNA transcript levels demonstrated that
      low PIAS3 levels predicted poor survival; Cox regression analysis revealed a
      hazard ratio of 0.57 (95% CI: 0.37-0.87), indicating a decrease in the risk of
      death by 43% for every unit elevation in PIAS3 gene expression. Curcumin
      treatment increased endogenous PIAS3 expression and decreased cell growth and
      viability in Calu-1 cells, a model of SCC. Our results implicate PIAS3 loss in
      the pathology of lung SCC and raise the therapeutic possibility of upregulating
      PIAS3 expression as a single target that can suppress signaling from the multiple
      receptor tyrosine kinase receptors found to be amplified in SCC. 

PMID- 25573686
TI  - MDCT diagnosis of acute pulmonary embolism in the emergent setting.
AB  - To compare utilization of CT pulmonary angiogram (CTA) for diagnosis of pulmonary
      embolism (PE) in an emergency department (ED) with unstructured CT ordering to
      published rates of CT positivity in other EDs including those employing decision
      support and to identify pathways for improved utilization via collaboration with
      our pathology and ED colleagues. Two hundred seventeen patients over a 2.5-month
      time period who received a CTA for PE were reviewed with exclusion of pediatric
      patients and all sub-optimal, non-diagnostic, or equivocal scans; 21 were
      excluded leaving a sample of 196 patients. The rate of PE diagnosis and
      association of PE positivity with selected factors (D-dimer testing) was
      assessed. The percentage of cases positive for PE was 10.7 % (21/196) which is
      similar to the frequently published rate of 10 % in other emergency departments
      including settings that have studied the use of decision support. D-dimer testing
      was performed in 40.3 % of cases. In 29.6 % (58/196) of subjects, D-dimer was
      positive, 10.7 % (21/196) was negative, and 59.7 % (117/196) was not assessed.
      Prevalence of PE among D-dimer negative (0 %, 0/21) was lower versus positive D
      dimer (12.1 %, 7/58) and unknown D-dimer patients (12.0 %, 14/117). D-dimer had
      100 % (21/21) negative predictive value for the diagnosis of PE. While this
      suggests that D-dimer is useful to rule-out PE, due to the small number of
      patients with PE, the 95 % confidence intervals are wide and the post-test
      likelihood of PE could be as high as 14 %. The rate of CT positivity for PE in an
      ED with unstructured CT ordering is similar to that in other published series
      including as series in which decision support was used. While D-dimer had high
      negative predictive value, large studies are needed to confirm this high
      sensitivity and potentially increase its use in ruling out PE without CT and to
      reduce CT ordering particularly in patients with sufficiently low clinical pre
      test probability of PE. 

PMID- 25573687
TI  - The role of latency period in quality management for free-breathing coronary wall
      MRI.
AB  - The aim of the present study was to determine the effects of the latency period
      on the performance of free-breathing coronary wall MRI. With the approval of IRB,
      70 participants were recruited for coronary wall magnetic resonance imaging (MRI)
      and provided written informed consent. In 35 subjects, right coronary segments
      (RCA1-3) were imaged first; in the remaining subjects, the left coronary segments
      (LM and LAD1-3) were imaged first. The images were classified into groups; group
      1 contained right coronary images from the subjects whose right coronary segments
      were imaged first and left coronary images from the subjects whose left coronary
      segments were imaged first. Group 2 contained the other coronary segments. The
      image scores (ranked1-3), latency periods, drift of the position of the navigator
      (NAV), scan efficiency were compared between image groups. Image group 1 has
      higher scores (1.66 +/- 0.55 vs. 1.46 +/- 0.51), shorter latency periods (32.04
      +/- 4.24 vs. 44.22 +/- 5.57 min), lower drift in the location of the NAV (1.90 +/
      1.27 mm vs. 2.61 +/- 1.71 mm) and higher scan efficiency (32.7 +/- 7.6 vs. 29.9
      +/- 7.9%) than group 2. Long latency periods have a significantly negative impact
      on the image quality of coronary wall MRI.

PMID- 25573688
TI  - Deep vein thrombosis and pulmonary embolism after solid organ transplantation: an
      unresolved problem.
AB  - Venous thromboembolism (VTE) is a major complication after solid organ
      transplantation (SOT), with an incidence that ranges from 2 to 34%. Besides
      genetic risk factors such as inherited thrombophilia, other specific risk factors
      for VTE in SOT recipients include impairment of fibrinolysis produced by
      corticosteroids, in vitro procoagulant effects of calcineurin inhibitors,
      endothelial damage due to cytomegalovirus infection, and specific surgical
      factors. Prevention strategies have not been systematically studied. Therefore,
      it is mandatory for the international scientific community to conduct large,
      multicenter, randomized clinical trials to define strategies for the prevention
      of VTE in SOT recipients. 

PMID- 25573689
TI  - Skeletal muscles respond differently when piglets are offered a diet 30%
      deficient in total sulfur amino acid for 10 days.
AB  - PURPOSE: Although amino acids (AA) are required for growth, little is known about
      the effect of a deficient AA supply on the composition and the contractile and
      metabolic properties of skeletal muscles. METHODS: Protein metabolism, oxidative
      catabolism, glutathione system, and fiber-type composition of the longissimus
      (LM), rhomboideus (RM), and semitendinous (SM) muscles were compared between 42
      day-old piglets pair-fed for 10 days either with a diet with a 28% deficient
      supply of total sulfur AA (TSAA-) or with a diet with a sufficient supply of
      total sulfur AA (TSAA+). RESULTS: The relative weight, protein mass, and protein
      synthesis of LM were 10-32% lower in TSAA- pigs compared with TSAA+ pigs, while
      RM and SM were not affected by the TSAA supply. The TSAA supply affected the AA
      composition of muscles. Concentrations of Met and branched-chain AA were,
      respectively, 7 and 3% lower in TSAA- pigs compared with TSAA+ pigs. The His
      concentration was 30% higher in LM and SM in TSAA- pigs compared with TSAA+ pigs
      and unaffected in RM. The activity of citrate synthase was 14% higher in all
      three muscles of TSAA- pigs. In these pigs, the beta-hydroxy-acyl-CoA
      dehydrogenase activity was 20% higher in RM compared with TSAA+ pigs while that
      of lactate dehydrogenase was 21% lower in LM. Total and reduced glutathione
      concentrations were more than 70% greater in RM than in LM or SM, and these
      concentrations were approximately 10% lower in TSAA- pigs than in TSAA+ pigs.
      CONCLUSIONS: Results of this study indicate that a TSAA deficiency affects muscle
      properties in a muscle-dependent manner increasing the oxidative capacity of RM
      and reducing growth and glycolytic metabolism of LM.

PMID- 25573690
TI  - Early and midterm results of transapical and right axillary artery cannulation
      for acute aortic dissection.
AB  - BACKGROUND: We combined transapical cannulation and right axillary artery
      cannulation in the repair of acute type A aortic dissection in order to reduce
      mortality and morbidity in the presence of risk of malperfusion. Early and
      midterm outcomes were evaluated. METHODS: Between October 2009 and March 2012, 23
      aortic dissection patients (age, 54.3 +/- 13.5 years) received graft replacement
      using a combination of transapical and right axillary artery cannulation.
      Preoperative malperfusion was present in 16 patients (69.6%). Cardiopulmonary
      bypass was initiated with axillary artery cannulation applied via the right
      axilla and right atrial drainage, then aotric cannulation applied via the left
      ventricular apex. We retrospectively investigated mortality and morbidity as well
      as cardiac function, which were evaluated echocardiographically during
      hospitalization and once a year postoperatively. RESULTS: All patients received
      total arch replacement. In-hospital mortality was 4.3%, and no patient developed
      intraoperative malperfusion. Intraoperative stroke occurred in one patient
      (4.3%), and three patients (13.0%) suffered from delayed stroke (10-24 days).
      These delayed strokes might have resulted from cardiogenic thrombus, although no
      intracardiac thrombus was found. Mean ejection fraction was 66.1 +/- 10.9% in the
      early postoperative period and 73.1 +/- 8.7% midterm. There was no left
      ventricular asynergy or intracardiac thrombus seen on either early or midterm
      echocardiography. CONCLUSION: Transapical cannulation with right axillary artery
      cannulation is a safe and effective procedure that can reduce operative risk
      associated with aortic dissection. Although transapical cannulation does not
      appear to impair cardiac function, it may confer a risk of delayed stroke.

PMID- 25573691
TI  - Neuregulin 1 affects leptin levels, food intake and weight gain in normal-weight,
      but not obese, db/db mice.
AB  - AIM: Studies in vitro have highlighted the potential involvement of neuregulin 1
      (NRG1) in the regulation of energy metabolism. This effect has also been
      suggested in vivo, as intracerebroventricular injection of NRG1 reduces food
      intakes and weight gain in rodents. Thus, it was hypothesised that NRG1 might
      affect serum leptin levels in mice. METHODS: Weight, food intakes, energy
      expenditure, spontaneous physical activity and serum leptin levels were evaluated
      in normal-weight C57BL/6JRJ mice following intraperitoneal administration of NRG1
      (50 MUg/kg, three times/week) or saline for 8 weeks. Based on the results of this
      first experiment, leptin-resistant obese db/db mice were then given NRG1 for 8
      weeks. RESULTS: Leptin serum concentrations were six times higher in C57BL/6JRJ
      mice treated with NRG1 than in the animals given saline. NRG1 treatment also
      reduced weight gain by 10% and food intakes by 15% compared with saline
      treatment, while energy expenditure remained unchanged. In db/db mice, serum
      leptin concentrations, weight gain, food intakes, energy expenditure and
      spontaneous physical activity were not altered by NRG1 treatment. CONCLUSION: The
      decrease in food intakes and weight gain associated with NRG1 treatment in
      C57BL/6JRJ mice may be partly explained by increased leptin levels, whereas db/db
      mice were not affected by the treatment, suggesting resistance to NRG1 in this
      pathological state.

PMID- 25573692
TI  - Tetramic acid derivatives and polyphenols from sponge-derived fungus and their
      biological evaluation.
AB  - Fifteen compounds, including two tetramic acid derivatives, penicillenol A1 (1)
      and penicillenol A2 (2), six polyphenols containing both phenolic bisabolane
      sesquiterpenoid and diphenyl ether units, expansols A-F (3-8), together with six
      phenolic bisabolane sesquiterpenoids (9-14) and diorcinol (15), were isolated
      from the fermentation broth of the marine-derived fungus ZSDS1-F11 isolated from
      the sponge Phakellia fusca Thiele collected in the Yongxing island of Xisha.
      Their structures were elucidated mainly by using extensive NMR spectroscopic and
      mass spectrometric analyses. Compounds 3-5, 7 and 8 showed potent COX-1
      inhibitory activity with IC50 values of 5.3, 16.2, 30.2, 41.0 and 56.8 MUM,
      respectively. Meanwhile, compounds 3-8 showed potent COX-2 inhibitory activity
      with IC50 values of 3.1, 5.6, 3.0, 5.1, 3.2 and 3.7 MUM, respectively. In
      addition, compound 1 exhibited antituberculosis activity with 96.1% inhibition at
      concentration of 10 MUM.

PMID- 25573693
TI  - Insecticidal and repellent activity of Clausena dentata (Rutaceae) plant extracts
      against Aedes aegypti and Culex quinquefasciatus mosquitoes (Diptera: Culicidae).
AB  - Mosquito control is facing a threat due to the emergence of resistance to
      synthetic insecticides. Insecticides of botanical origin may serve as suitable
      alternative biocontrol agents. The present study is to evaluate adulticidal
      activity of Clausena dentata plant extract against Aedes aegypti and Culex
      quinquefasciatus mosquitoes. The adult mortality was observed after 24 h of
      exposure. The highest mortality was found in acetone extracts against Ae. aegypti
      and Cx. quinquefasciatus with the LC50 and LC90 4.1783 mg/ml (3.8201-7.1026),
      9.3884 mg/ml (7. 8258-13.1820) and 4.2451 mg/ml (3.8547-8.0254), 12.3214 mg/ml
      (10.9287-16.2220), respectively. Smoke toxicity was observed at 10-min interval
      for 40 min, and the mortality data were recorded. Result shows that Ae. aegypti
      and Cx. quinquefasciatus are 85 +/- 2 and 89 +/- 1.5, respectively. A mortality
      of 100 % was recorded in the commercial mosquito control. These results suggest
      that the leaf extracts of C. dentata have a potential to be used as an ideal eco
      friendly approach for the control of mosquitoes.

PMID- 25573695
TI  - Morphological aspects of Henneguya aequidens n. sp. (Myxozoa: Myxobolidae) in
      Aequidens plagiozonatus Kullander, 1984 (Teleostei: Cichlidae) in the Amazon
      region, Brazil.
AB  - A new species of Myxosporea, Henneguya aequidens sp. n. (Myxozoa: Myxobolidae),
      was described based on its ultrastructural features. This is a parasite of the
      freshwater fish Aequidens plagiozonatus, in the Peixe-boi River, Para, Brazil.
      This parasite was found in the gills, in the form of whitish ellipsoid cysts with
      mature spores inside them. The average spore body was 15 +/- 0.9 MUm in length (n
      = 30) and 6 +/- 0.8 MUm in width (n = 30), and the tail measured 27 +/- 0.5 MUm
      in length (n = 15). The spores showed typical features of the genus Henneguya
      with two valves of equal size and two symmetrical polar capsules of 3 +/- 0.3 MUm
      in length and 2 +/- 0.3 MUm in width. Each polar capsule had a polar filament
      forming a helix from the apical region to the polar caps, with four to six turns.
      Based on the ultrastructural differences in morphology of these spores, the
      location of the parasite, and its host specificity, this parasite was described
      as a new species.

PMID- 25573694
TI  - Isoforms of Hsp70-binding human LDL in adult Schistosoma mansoni worms.
AB  - Schistosoma mansoni is one of the most common parasites infecting humans. They
      are well adapted to the host, and this parasite's longevity is a consequence of
      effective escape from the host immune system. In the blood circulation,
      lipoproteins not only help to conceal the worm from attack by host antibodies but
      also act as a source of lipids for S. mansoni. Previous SEM studies showed that
      the low-density lipoprotein (LDL) particles present on the surface of adult S.
      mansoni worms decreased in size when the incubation time increased. In this
      study, immunocytochemical and proteomic analyses were used to locate and identify
      S. mansoni binding proteins to human plasma LDL. Ultrathin sections of adult
      worms were cut transversely from the anterior, medial and posterior regions of
      the parasite. Immunocytochemical experiments revealed particles of gold in the
      tegument, muscle region and spine in male worms and around vitelline cells in
      females. Immunoblotting and 2D-electrophoresis using incubations with human
      serum, anti-LDL antibodies and anti-chicken IgG peroxidase conjugate were
      performed to identify LDL-binding proteins in S. mansoni. Analysis of the binding
      proteins using LC-MS identified two isoforms of the Hsp70 chaperone in S.
      mansoni. Hsp70 is involved in the interaction with apoB in the cytoplasm and its
      transport to the endoplasmic reticulum. However, further studies are needed to
      clarify the functional role of Hsp70 in S. mansoni, mainly related to the
      interaction with human LDL.

PMID- 25573696
TI  - Longer-term outcome of perventricular device closure of muscular ventricular
      septal defects in children.
AB  - OBJECTIVE: To describe the longer-term clinical experience and follow-up with
      perventricular device closure of ventricular septal defects (VSD) in children.
      METHODS: Between January 2005 and December 2013, muscular ventricular septal
      defect closure with the Amplatzer Muscular VSD Occluder was undertaken using a
      hybrid perventricular approach. Data including demographic, echocardiographic
      parameter, and clinical outcome were reviewed retrospectively. RESULTS: Median
      age at the time of procedure was 8.9 months (range 1.9-31.0 months) and median
      weight was 6.6 kg (range 4.5-12.9 kg). All had a moderate to large muscular VSD,
      three had more than one VSD, four had previous coarctation repair, and five had
      previous pulmonary artery (PA) banding. A single Amplatzer muscular occluder
      (range 8-18 mm) was deployed in each patient without cardiopulmonary bypass under
      echocardiographic guidance. Two of ten patients subsequently required a short
      period of cardiopulmonary bypass for reconstruction of PA after de-banding and
      closure of atrial septal defect in one. Occluder removal was necessary in one
      patient due to entrapment of the tricuspid valve and progressive tricuspid
      regurgitation. This patient underwent surgical repair with a good result and no
      device-related valve damage. In the remaining nine patients, no severe
      complications such as device embolization, arrhythmia, or significant valve
      regurgitation were noted in the post-operative period or follow-up. At a median
      time of 6.5 years (range 0.9-8.4 years) post device implantation, complete
      closure was achieved in five patients and four had small residual leaks, which
      were not hemodynamically significant. CONCLUSION: Perventricular muscular VSD
      closure is effective in small children with suitable muscular defects and may
      avoid the morbidity associated with cardiopulmonary bypass and conventional
      surgical repair. There have been no late complications with this approach.

PMID- 25573697
TI  - Lack of drug interaction between cyclosporine and telaprevir in a liver
      transplant recipient.
AB  - Telaprevir is a novel NS3A/4A protease inhibitor approved in combination with
      ribavirin and peg-interferon alfa for the treatment of genotype-1 chronic
      hepatitis C. This drug is also known to be a potent cytochrome P450 3A and drug
      efflux protein ATP-binding cassette B1 (also called P-glycoprotein) inhibitor,
      and could therefore interact with immunosuppressive drugs. For this reason, a
      decrease in cyclosporine (CsA) dosage has been proposed when combining this drug
      with telaprevir. We report herein the case of an unpredictable lack of
      interaction between CsA and telaprevir in a liver transplant recipient. The
      decrease in CsA dosage, conducted as recommended in the literature, did not
      result in stable CsA concentrations but decreased them. However, the decrease in
      CsA exposure could have been unseen without the measurement of CsA concentrations
      2 h after the administration (C2 ) of the drug, because it mainly resulted from
      the decrease in CsA peak. The mechanism leading to this lack of drug interaction
      in this patient has not been fully elucidated yet, but is likely to affect the
      absorption phase. Therapeutic drug monitoring using only CsA trough
      concentrations could be falsely reassuring, and the addition of the measurement
      of the C2 may add useful information to adapt CsA dosage in patients co-treated
      with telaprevir. 

PMID- 25573698
TI  - Bifunctional polyacrylonitrile fiber-mediated conversion of sucrose to 5
      hydroxymethylfurfural in mixed-aqueous systems.
AB  - A highly efficient catalytic system composed of a bifunctional polyacrylonitrile
      fiber (PANF-PA[BnBr]) and a metal chloride was employed to produce 5
      hydroxymethylfurfural (HMF) from sucrose in mixed-aqueous systems. The promoter
      of PANF-PA[BnBr] incorporates protonic acid groups that promote the hydrolysis of
      the glycosidic bond to convert sucrose into glucose and fructose, and then
      catalyzes fructose dehydration to HMF, while the ammonium moiety may promote
      synergetically with the metal chloride the isomerization of glucose to fructose
      and transfer HMF from the aqueous to the organic phase. The detailed
      characterization by elemental analysis, FTIR spectroscopy, and SEM confirmed the
      rangeability of the fiber promoter during the modification and utilization
      processes. Excellent results in terms of high yield (72.8%) of HMF, superior
      recyclability (6 cycles) of the process, and effective scale-up and simple
      separation procedures of the catalytic system were obtained. Moreover, the
      prominent features (high strength, good flexibility, etc.) of the fibers are very
      attractive for fix-bed reactor.

PMID- 25573699
TI  - C-reactive protein, depressive symptoms and incident diabetes mellitus with
      special emphasis on physical activity.

PMID- 25573700
TI  - Nesting behavior is associated with VIP expression and VIP-Fos colocalization in
      a network-wide manner.
AB  - Many species, including humans, engage in a series of behaviors that are
      preparatory to the arrival of offspring. Such "nesting behaviors" are of obvious
      importance, but relevant neuroendocrine mechanisms remain little studied. We here
      focus on the potential roles of vasoactive intestinal polypeptide (VIP) in the
      performance of appetitive and consummatory nesting behaviors in male and female
      zebra finches (Taeniopygia guttata). Using combined immunocytochemistry for Fos
      and in situ hybridization for VIP, we now show that many VIP cell groups show
      increased transcriptional activity in response to nest building in male and
      female zebra finches. Particularly strong data come from the preoptic area
      (medial preoptic area and medial preoptic nucleus), where VIP-Fos co-expression
      correlates positively with three different measures of nesting behavior, as does
      the number of VIP-expressing cells. Remarkably, we find that VIP mRNA and/or VIP
      Fos co-expression is correlated with nesting behavior in virtually every brain
      area that we examined, including the medial amygdala (anterior and posterior),
      medial bed nucleus of the stria terminalis, medial preoptic area, medial preoptic
      nucleus, anterior hypothalamus, ventromedial hypothalamus, periaqueductal gray
      complex (central gray and nucleus intercollicularis), and ventral tegmental area.
      Near-significant effects are also obtained in the tuberoinfundibular
      hypothalamus. Although most correlations are positive, negative correlations are
      observed for the VIP cell group of the anterior hypothalamus, a population that
      selectively promotes aggression, and also the periaqueductal gray complex. These
      data demonstrate a network-wide relationship between peptide production and
      social behavior that is, to our knowledge, unparalleled by other peptidergic
      modulators. 

PMID- 25573702
TI  - Genomic sequencing and microsatellite marker development for Boswellia
      papyrifera, an economically important but threatened tree native to dry tropical
      forests.
AB  - Microsatellite (or simple sequence repeat, SSR) markers are highly informative
      DNA markers often used in conservation genetic research. Next-generation
      sequencing enables efficient development of large numbers of SSR markers at lower
      costs. Boswellia papyrifera is an economically important tree species used for
      frankincense production, an aromatic resinous gum exudate from bark. It grows in
      dry tropical forests in Africa and is threatened by a lack of rejuvenation. To
      help guide conservation efforts for this endangered species, we conducted an
      analysis of its genomic DNA sequences using Illumina paired-end sequencing. The
      genome size was estimated at 705 Mb per haploid genome. The reads contained one
      microsatellite repeat per 5.7 kb. Based on a subset of these repeats, we
      developed 46 polymorphic SSR markers that amplified 2-12 alleles in 10 genotypes.
      This set included 30 trinucleotide repeat markers, four tetranucleotide repeat
      markers, six pentanucleotide markers and six hexanucleotide repeat markers.
      Several markers were cross-transferable to Boswellia pirrotae and B. popoviana.
      In addition, retrotransposons were identified, the reads were assembled and
      several contigs were identified with similarity to genes of the terpene and
      terpenoid backbone synthesis pathways, which form the major constituents of the
      bark resin. 

PMID- 25573701
TI  - Low health literacy predicts decline in physical function among older adults:
      findings from the LitCog cohort study.
AB  - BACKGROUND: Limited health literacy is associated with worse physical function in
      cross-sectional studies. We aimed to determine if health literacy is a risk
      factor for decline in physical function among older adults. METHODS: A
      longitudinal cohort of 529 community-dwelling American adults aged 55-74 years
      were recruited from an academic general internal medicine clinic and federally
      qualified health centres in 2008-2011. Health literacy (Newest Vital Sign), age,
      gender, race, education, chronic conditions, body mass index, alcohol
      consumption, smoking status and exercise frequency were included in multivariable
      analyses. The 10-item PROMIS (Patient-Reported Outcomes Measurement Information
      System) physical function scale was assessed at baseline and follow-up (mean=3.2
      years, SD=0.39). RESULTS: Nearly half of the sample (48.2%) had either marginal
      (25.5%) or low health literacy (22.7%). Average physical function at baseline was
      83.2 (SD=16.6) of 100, and health literacy was associated with poorer baseline
      physical function in multivariable analysis (p=0.004). At follow-up, physical
      function declined to 81.9 (SD=17.3; p=0.006) and 20.5% experienced a meaningful
      decline (>0.5 SD of baseline score). In multivariable analyses, participants with
      marginal (OR 2.62; 95%CI 1.38 to 4.95; p=0.003) and low (OR 2.57; 95%CI 1.22 to
      5.44; p=0.013) health literacy were more likely to experience meaningful decline
      in physical function than the adequate health literacy group. Entering cognitive
      abilities to these models did not substantially attenuate effect sizes. Health
      literacy attenuated the relationship between black race and decline in physical
      function by 32.6%. CONCLUSIONS: Lower health literacy increases the risk of
      exhibiting faster physical decline over time among older adults. Strategies that
      reduce literacy disparities should be designed and evaluated.

PMID- 25573703
TI  - Pretreatment With L-Citrulline Positively Affects the Mucosal Architecture and
      Permeability of the Small Intestine in a Murine Mucositis Model.
AB  - BACKGROUND: Mucositis is a common complication in patients undergoing
      radiotherapy and chemotherapy. It is associated with pain, poor quality of life,
      and malnutrition, leading to an increased number of hospital admissions and
      prolonged hospitalization. The use of immunonutrients may be an alternative
      treatment option, which may help to improve patient outcome. OBJECTIVE: Here we
      assessed the impact of L-citrulline (CIT) on a murine model of 5-fluorouracil
      (5FU)-induced mucositis. METHODS: Swiss male mice were randomized into 4 groups:
      control, CIT, 5FU, and 5FU+CIT. Mice were fed with commercial chow and
      supplemented with an oral solution of alanine (control and 5FU groups) or CIT
      (CIT and 5FU+CIT groups). On the seventh day, mice received intraperitoneal
      phosphate-buffered saline or 5FU (200 mg/kg, single dose) to induce mucositis. On
      the 10th day, mice were euthanized, and the blood and small intestines were
      harvested. Body weight, morphology, histopathology score (hematoxylin and eosin)
      of the small intestine (from 0-12), myeloperoxidase activity, oxidative stress
      level, and intestinal permeability were assessed. RESULTS: We observed
      significant weight loss after the administration of 5FU in both treated and
      control animals. CIT administration contributed to a partial recovery of the
      mucosal architecture as well as an intermediate reduction of the histopathologic
      score, and functional intestinal permeability was partially rescued. CONCLUSIONS:
      CIT administration attenuated 5FU-mediated damage to the mucosal architecture of
      the small intestine, decreasing the size of the injured areas and promoting
      decreased intestinal permeability.

PMID- 25573704
TI  - Comparison between two different modes of non-invasive ventilatory support in
      preterm newborn infants with respiratory distress syndrome mild to moderate:
      preliminary data.
AB  - Despite of improved survival of premature infants, the incidence of long term
      pulmonary complications, mostly associated with ventilation-induced lung injury,
      remains high. Non invasive ventilation (NIV) is able to reduce the adverse
      effects of mechanical ventilation. Although nasal continuous positive airway
      pressure (NCPAP) is an effective mode of NIV, traumatic nasal complications and
      intolerance of the nasal interface are common. Recently high flow nasal cannula
      (HFNC) is emerging as a better tolerated form of NIV, allowing better access to
      the baby's face, which may improve nursing, feeding and bonding. HFNC may be
      effective in the treatment of some neonatal respiratory conditions while being
      more user-friendly for care-givers than conventional NCPAP. Limited evidence is
      available to support the specific role, efficacy and safety of HFNC in newborns
      and to demonstrate efficacy compared with NCPAP; some studies suggest a potential
      role for HFNC in respiratory care of the neonate as a distinct non invasive
      ventilatory support. We present the preliminary data of a randomized clinical
      trial; the aim of this study was to assess efficacy and safety of HFNC compared
      to NCPAP in preterm newborns with mild to moderate respiratory distress syndrome
      (RDS). 

PMID- 25573705
TI  - Why open surgery for treatment of paediatric varicocele?
AB  - The high surgical ligature of spermatic vessels modified Palomo and the antegrade
      sclerotherapy according to Tauber represent two therapeutic modalities at last
      assured. In the experience of the Author the surgical technique is better with
      regard to the appearance of relapsing varicocele and the mean operative time. 

PMID- 25573706
TI  - Cutis marmorata telangiectatica congenita in a preterm female newborn: case
      report and review of the literature.
AB  - Cutis Marmorata Telangiectatica Congenita (CMTC) is a rare, sporadic condition
      usually present at birth characterized by localized or generalized persistent
      cutis marmorata, telangiectasia and phlebectasia. We report a preterm female
      newborn, the third child of non-related caucasian parents, with CMTC at birth who
      showed typical cutaneous features and monolateral congenital glaucoma. The
      pathogenesis of this disorder is unknown and the cause is probably
      multifactorial. Teratogens and autosomal dominant mode of inheritance with
      incomplete penetrance have been considered as etiological factors. Prognosis, in
      uncomplicated cases, is good. 

PMID- 25573707
TI  - Evans Syndrome: A case report.
AB  - We describe a case of a 14-years old caucasian female affected by autoimmune
      hemolytic anemia and thrombocytopenia successfully treated with intravenous
      immunoglobulin and steroids. Nevertheless, neutropenia occurred during follow-up
      period. Positivity of direct antiglobulin test and sieric anti-neutrophil
      antibodies suggested the diagnosis of Evans syndrome trilineage. 

PMID- 25573708
TI  - Nephrogenic remnants: occasional ultrasound diagnosis and follow-up.
AB  - Nephrogenic remnants (NRs) are nodular collections of undifferentiated renal
      blastema cells in the postnatal kidney that are recognized as putative precursor
      lesions of Wilms tumor (WT). NRs may remain stationary, undergo regression, or
      proliferate. In the last case, there is a high risk for the development of a WT.
      During infancy, they are most frequently of microscopic size, to be found only at
      autopsy in approximately 1% of infant kidneys. Approximately 1 out of 100
      microscopic lesions persist and grow developing lesions large enough to be seen
      by ultrasound in the first months of life. We report on a case of NRs in a six
      year old child, as incidental finding during abdominal ultrasound performed for
      other purposes. In consideration of the potential evolution in WT, after a period
      of close surveillance of 14 months, the lesion was resected. Histological
      examination revealed the presence of NRs, no neoplastic lesions were found.
      Currently the patient is 16 years old, in good health, and there have been no
      signs of recurrence. 

PMID- 25573709
TI  - Transumbilical laparoscopic treatment of Congenital Infantile Fibrosarcoma of the
      Ileum.
AB  - Congenital-Infantile Fibrosarcoma (CIF) is a malignant mesenchymal tumor
      representing 10-20% of soft-tissue tumors. Complete surgical resection is
      generally the treatment of choice. The most recurrent cytogenetic abnormality was
      identified as the traslocation t(12;15)(p13:q25), which bears the fusion of Tel
      gene EVT6 with TrkC gene. This study describes a case of infantile fibrosarcoma
      of the ileum in a female newborn examined for intestinal occlusion and its
      laparoscopic treatment. 

PMID- 25573710
TI  - Paediatricians' attitudes toward pain in children with severe cognitive
      impairment. A regional survey.
AB  - INTRODUCTION: pain is a frequent and relevant problem in children with severe
      cognitive impairments. Assessing pain in these patients can be difficult.
      Specific observational tools such as the Collignon Giusiano Questionnaire or the
      Non-communicating Children's Pain Checklist ( NCCPC) are available, but their use
      is not widespread. Children with severe cognitive impairment are frequently in
      need of painful procedures but data about availability of procedural sedation in
      this setting are limited. OBJECTIVE OF THE STUDY: to evaluate paediatricians'
      attitudes toward pain in children with severe cognitive impairment by measuring
      the use of specific pain scales and the use of analgesia or procedural sedation
      in course of a frequent procedure such as botulinum toxin injection. METHODS:
      phone interview with the doctor on duty of 56 paediatric wards in 3 regions of
      the North East of Italy, addressing the routine use of pain scales, and the use
      of specific observational tools for non communicating children. A phone interview
      was also conducted in 4 centers routinely practicing botulinum toxin injection
      about the use of analgesia or procedural sedation. RESULTS: 1 centre out of 55
      reported to use specific scales for children with cognitive impairment,
      specifically the Collignon Giusiano Questionnaire. No centre used procedural
      sedation for botulinum toxin injection. CONCLUSION: in the investigated area
      there is a lack of attention to pain in children with severe cognitive
      impairment. Specific educational efforts should be done to improve the quality of
      care in this setting.

PMID- 25573711
TI  - Generalized aggressive periodontitis in prepubertal age: description and
      comparison of two cases.
AB  - Aggressive periodontitis is a rare form of periodontal disease and it can involve
      both the deciduous dentition and the permanent one. It causes a rapid loss of
      periodontal attachment. The paper aims to describe two cases of severe
      generalized prepubertal periodontitis: the first child doesn't suffer from
      neither systemic diseases nor alteration of functionality of polymorphonuclear
      and periodontal disease involved both his deciduous dentition and the first
      permanent molars. The second child had a deficiency of functionality of
      polymorphonuclear but periodontal disease involved only primary dentition thanks
      to his immediate improvement of home dental hygiene. This comparison shows the
      importance of early diagnosis and especially of optimal dental oral hygiene.
      Infant healthcare professionals, as pediatric dentists and pediatricians, should
      have the necessary knowledge for early and correct diagnosis and clinical
      management of disease. 

PMID- 25573712
TI  - Glial development and function in the nervous system of Caenorhabditis elegans.
AB  - The nematode, Caenorhabditis elegans, has served as a fruitful setting for
      understanding conserved biological processes. The past decade has seen the rise
      of this model organism as an important tool for uncovering the mysteries of the
      glial cell, which partners with neurons to generate a functioning nervous system
      in all animals. C. elegans affords unparalleled single-cell resolution in vivo in
      examining glia-neuron interactions, and similarities between C. elegans and
      vertebrate glia suggest that lessons learned from this nematode are likely to
      have general implications. Here, I summarize what has been gleaned over the past
      decade since C. elegans glia research became a concerted area of focus. Studies
      have revealed that glia are essential elements of a functioning C. elegans
      nervous system and play key roles in its development. Importantly, glial
      influence on neuronal function appears to be dynamic. Key questions for the field
      to address in the near- and long-term have emerged, and these are discussed
      within. 

PMID- 25573714
TI  - Sexually antagonistic zygotic drive: a new form of genetic conflict between the
      sex chromosomes.
AB  - Sisters and brothers are completely unrelated with respect to the sex chromosomes
      they inherit from their heterogametic parent. This has the potential to result in
      a previously unappreciated form of genetic conflict between the sex chromosomes,
      called sexually antagonistic zygotic drive (SA-ZD). SA-ZD can arise whenever
      brothers and sisters compete over limited resources or there is brother-sister
      mating coupled with inbreeding depression. Although theory predicts that SA-ZD
      should be common and influence important evolutionary processes, there is little
      empirical evidence for its existence. Here we discuss the current understanding
      of SA-ZD, why it would be expected to elude empirical detection when present, and
      how it relates to other forms of genetic conflict. 

PMID- 25573715
TI  - Reelin has a preventive effect on phencyclidine-induced cognitive and sensory
      motor gating deficits.
AB  - Reelin has recently attracted attention because of its connection to several
      neuropsychiatric diseases. We previously reported the finding that prior
      transplantation of GABAergic neuron precursor cells into the medial prefrontal
      cortex (mPFC) of mice significantly prevented the induction of cognitive and
      sensory-motor gating deficits induced by phencyclidine (PCP). The majority of the
      precursor cells transplanted into the mPFC of the recipient mice differentiated
      into members of a somatostatin/Reelin-expressing class of GABAergic interneurons.
      These findings raised the possibility that Reelin secreted by the transplanted
      cells plays an important role in preventing the deficits induced by PCP. In this
      study, we investigated whether Reelin itself has a preventive effect on PCP
      induced behavioral phenotypes by injecting conditioned medium containing Reelin
      into the lateral ventricle of the brains of 6- to 7-week-old male mice before
      administrating PCP. Behavioral analyses showed that the prior Reelin injection
      had a preventive effect against induction of the cognitive and sensory-motor
      gating deficits associated with PCP. Moreover, one of the types of Reelin
      receptor was found to be expressed by neurons in the mPFC. The results of this
      study point to the Reelin signaling pathway as a candidate target for the
      pharmacologic treatment of neuropsychiatric diseases. 

PMID- 25573713
TI  - Group 2 innate lymphoid cells in health and disease.
AB  - Group 2 innate lymphoid cells (ILC2s) play critical roles in anti-helminth
      immunity, airway epithelial repair, and metabolic homeostasis. Recently, these
      cells have also emerged as key players in the development of allergic
      inflammation at multiple barrier surfaces. ILC2s arise from common lymphoid
      progenitors in the bone marrow, are dependent on the transcription factors
      RORalpha, GATA3, and TCF-1, and produce the type 2 cytokines interleukin (IL)-4,
      IL-5, IL-9, and/or IL-13. The epithelial cell-derived cytokines IL-25, IL-33, and
      TSLP regulate the activation and effector functions of ILC2s, and recent studies
      suggest that their responsiveness to these cytokines and other factors may depend
      on their tissue environment. In this review, we focus on recent advances in our
      understanding of the various factors that regulate ILC2 function in the context
      of immunity, inflammation, and tissue repair across multiple organ systems. 

PMID- 25573717
TI  - Positron emission tomography imaging of the social brain of common marmosets.
AB  - Positron emission tomography (PET) is a molecular imaging modality that can
      visualize functional neurochemical processes throughout the brain in the living
      condition, and is useful in bridging the gap between experimental animals and
      humans. We applied PET to common marmosets to study the brain mechanisms
      underlying social behaviors. Common marmosets are known for their high level of
      sociality within a cooperative breeding system, which is rare among non-human
      primates, and they could represent valuable animals for studying human-like
      social behaviors. PET successfully revealed a brain-molecular relationship
      underlying social traits and a functional brain network associated with social
      situations in common marmosets. Marmoset PET appears likely to prove useful in
      understanding the neurobiological mechanisms underpinning social behaviors in
      both physiological and pathological conditions, and has potential for simulating
      psychiatric disorders. 

PMID- 25573716
TI  - Mini-atlas of the marmoset brain.
AB  - A mini-atlas of the brain is designed to help students and young researchers who
      are not familiar with neuroanatomy. In the mini-atlas, a limited number of
      important nuclei and fiber tracts are shown on a small number of brain sections
      from posterior end to the anterior end of the brain. The first mini-atlas was
      introduced for the rat brain (Watson et al., 2010). Here we present a mini-atlas
      of the common marmoset (Callithrix jaccus), which is one of representative
      experimental primates for modern neuroscience. We further discuss the differences
      of brain structures between rodents and primates. 

PMID- 25573718
TI  - The olfactory bulb and the number of its glomeruli in the common marmoset
      (Callithrix jacchus).
AB  - The olfactory system has been well studied in mammals such as mice and rats.
      However, few studies have focused on characterizing this system in diurnal
      primates that rely on their sense of smell to a lesser extent due to their
      ecological environment. In the present study, we determined the histological
      organization of the olfactory bulb in the common marmoset (Callithrix jacchus).
      We then constructed 3-dimensional models of the glomeruli of the olfactory bulb,
      and estimated the number of glomeruli. Olfactory glomeruli are the functional
      units of olfactory processing, and have been investigated in detail using mice.
      There are approximately 1800 glomeruli in a mouse hemibulb, and olfactory sensory
      neurons expressing one selected olfactory receptor converge onto one or two
      glomeruli. Because mice have about 1000 olfactory receptor genes, it is proposed
      that the number of glomeruli in mammals is nearly double that of olfactory
      receptor genes. The common marmoset carries only about 400 intact olfactory
      receptor genes. The present study revealed that the number of glomeruli in a
      marmoset hemibulb was approximately 1500-1800. This result suggests that the
      number of glomeruli is not positively correlated with the number of intact
      olfactory receptor genes in mammals. 

PMID- 25573719
TI  - Psychologic adjustment to irreversible vision loss in adults: a systematic
      review.
AB  - PURPOSE: To summarize relevant evidence investigating the psychologic adjustment
      to irreversible vision loss (IVL) in adults. DESIGN: Irreversible vision loss
      entails a challenging medical condition in which rehabilitation outcomes are
      strongly dependent on the patient's psychologic adjustment to illness and
      impairment. So far, no study has systematically reviewed the psychologic
      adjustment to IVL in adults. METHODS: We reviewed all articles examining the
      psychologic adjustment to IVL in adults. We included articles published in
      English in peer-reviewed journals. We performed a keyword literature search using
      4 databases (PubMed, EBSCO, Cochrane Library, and Science Direct) for all years
      through July 2014. We assessed risk of bias of selected studies using the RTI
      Item Bank for Assessing Risk of Bias and Confounding for Observational Studies of
      Interventions or Exposures and the Cochrane risk of bias tool for randomized
      controlled trials. RESULTS: Of a total of 3948 citations retrieved, we selected
      52 eligible studies published between 1946 and 2014. The majority of studies were
      observational and cross-sectional in nature. Our review suggests that high levels
      of depression occur during the adjustment to IVL. Better adjustment to IVL was
      associated with greater acceptance of vision loss and use of instrumental coping,
      good social support, positivity, and use of assistive aids. CONCLUSIONS: The
      overall findings indicate that IVL often has negative effects on patients'
      quality of life and mental health and that such effects tend to remain over time.
      Specific factors and variables associated with the adjustment to IVL need to be
      clarified through further in-depth and longitudinal research.

PMID- 25573720
TI  - Gastrointestinal problems in 15q duplication syndrome.
AB  - Chromosome 15q duplication syndrome (Dup15q syndrome) is a neurodevelopmental
      disorder involving copy number gains of the maternal chromosome 15q11.2-q13
      region, characterized by intellectual disability, developmental delay, autism
      spectrum disorder (ASD), and epilepsy. Gastrointestinal (GI) problems in Dup15q
      syndrome have been reported only rarely, mostly focused on neonatal feeding
      difficulties. A retrospective review of the medical records of 46 patients with
      Dup15q syndrome was conducted to assess GI issues and their treatments in this
      population. GI symptoms were present in 76.7% of subjects with an isodicentric
      duplication and 87.5% with an interstitial duplication. There was no clear
      association between GI issues and ASD, with symptoms occurring in 78.9% of all
      subjects and 78.2% of ASD subjects. The most commonly reported symptoms were
      gastroesophageal reflux (56.7%) and constipation (60%), with 30% of subjects
      reporting both. The most common treatments were polyethylene glycol for
      constipation and proton pump inhibitors for reflux. Behaviors such as
      irritability and aggressiveness improved with treatment of GI symptoms in several
      subjects. The results indicate that GI symptoms are common in Dup15q syndrome and
      may have an atypical presentation. Diagnosis may be difficult, especially in
      individuals who are nonverbal or minimally verbal, so increased awareness is
      critical for early diagnosis and treatment.

PMID- 25573721
TI  - Mitochondrial replacement therapy in reproductive medicine.
AB  - Mitochondrial dysfunction is implicated in disease and age-related infertility.
      Mitochondrial replacement therapies (MRT) in oocytes or zygotes, such as
      pronuclear (PNT), spindle (ST), or polar body (PBT) transfer, could prevent
      second-generation transmission of mitochondrial DNA (mtDNA) defects. PNT,
      associated with high levels of mtDNA carryover in mice but low levels in human
      embryos, carries ethical issues secondary to donor embryo destruction. ST,
      developed in primates, supports normal development to adults and low mtDNA
      carryover. PBT in mice, coupled with PN or ST, may increase the yield of
      reconstructed embryos with low mtDNA carryover. MRT also offers replacement of
      the deficient cytoplasm in oocytes from older patients, with the expectation of
      high pregnancy rates following in vitro fertilization. 

PMID- 25573722
TI  - Psychological distress, quality of life, symptoms and unmet needs of colorectal
      cancer survivors near the end of treatment.
AB  - PURPOSE: This study investigated psychological morbidity, quality of life (QoL),
      colorectal cancer (CRC)-specific symptoms and supportive care needs in a CRC
      population at the end of treatment (EOT). METHODS: CRC survivors (n = 152)
      completed a post-treatment baseline questionnaire as part of a multisite
      supportive care randomised controlled trial (SurvivorCare). CRC survivors had
      completed treatment with curative intent within 0 to 6 months. Measures are as
      follows: Brief Symptom Inventory 18 (BSI-18) (psychological morbidity), EORTC QLQ
      C30 and QLQ-CR29 (QoL and CRC-specific symptoms and problems) and Cancer
      Survivors' Unmet Needs (CaSUN) measure with a simplified response format (unmet
      needs). Linear regression models were used to compare participants' QoL with a
      general population sample. Correlation analysis examined associations between
      psychological morbidity, QoL and CRC-specific symptoms and problems. RESULTS:
      Average participant age was 64 years, and 51% were male. The majority (68%) had
      stage 3 disease. In comparison to population norms, CRC survivors had lower
      depression and anxiety scores (47.4 and 45.6, respectively) but higher
      somatisation, and lower role, cognitive and social functioning (p < 0.001). CRC
      survivors had higher fatigue, nausea/vomiting, appetite loss, diarrhoea and
      financial problems (all p < 0.001), as well as pain (p = 0.002) and constipation
      (p = 0.019). CRC-specific psychological scores were positively correlated with
      all three BSI domain scores, and pain and fatigue symptom scores on the QLQ-C30
      while negatively correlated with all five functional scales of the QLQ-C30.
      CONCLUSIONS: CRC survivors reported good mental health at EOT. Role and social
      functioning were impaired compared to population norms, possibly related to
      physical symptoms. IMPLICATIONS FOR CANCER SURVIVORS: Findings may help guide
      consultations with patients and inform the design of more tailored supportive
      care interventions. TRIAL REGISTRATION: ACTRN12610000207011.

PMID- 25573724
TI  - Antioxidants in health and disease.
AB  - Research on antioxidants proceeds at full speed after a partial decline of public
      interest, when claims on effectiveness of mega doses of vitamin C proved
      unfounded. The main role of antioxidants is to liquidate the uncontrolled
      production of reactive oxygen species (ROS) that is being linked to pathogenesis
      of cardiovascular disease (CVD), malignancy, diabetes type 2, mechanism of
      infection, fibrogenesis and some neurological disorders. This review summarizes
      the most recent reports on antioxidants, published since 2010. Follow up data on
      vitamins C and E focus on their potential for immune modulation and on
      endothelial nitric oxide bioavailability. Previously well established
      antioxidants carotenoids and polyphenols are still much in scientific interest.
      Interestingly, several antioxidants (for example rasveratrol and
      feruloylnoradrenaline) are generated in infected or injured plants. An intensive
      attention is directed to resveratrol. This compound, in addition to
      antioxidation, stimulates nitric oxid production, protects endothelial cells from
      oxidative functional damage, lowers platelet aggregation and directly inhibits
      cyclic adenosine monophosphate-specific phosphodiesterases. Recently discovered
      feruloylnoradrenaline in microbially infected tomatoes is reported to have 14
      times the antioxidant power of resveratrol. With all this new information, it is
      important to point out the prevailing opinion that additional supplements of
      antioxidants are not needed, as long as the organism has adequate stores of
      antioxidants and the diet is normal in composition and in quantity (Fig. 3, Ref.
      34).

PMID- 25573723
TI  - Health-related quality of life is associated with physical activity levels among
      colorectal cancer survivors: a longitudinal, 3-year study of the PROFILES
      registry.
AB  - PURPOSE: The present study aims to examine the longitudinal relation between
      physical activity (PA) and health-related quality of life (HRQoL) among
      colorectal cancer (CRC) survivors. METHODS: Individuals diagnosed with CRC
      between 2000 and 2009 as registered by the Dutch population-based Eindhoven
      Cancer Registry, and who were eligible for the study, received a questionnaire on
      three time points with 1-year intervals. Generalized linear mixed models were
      used to estimate the independent effects of PA on HRQoL over time. RESULTS:
      Response rates were 73% (n = 2625), 83% (n = 1643), and 82% (n = 1458) at T1, T2,
      and T3, respectively. PA behavior was relatively stable over time with 82% of the
      patients meeting the Dutch PA guidelines (at least 150 min of moderate to
      vigorous PA per week) at all assessment periods. Multivariate analyses showed
      that patients who met the PA guidelines scored, on average, 13.7 points higher on
      the global quality of life, 26.0 on physical, 24.2 on role, 9.0 on cognitive,
      10.4 on emotional, and 14.8 on social functioning over time compared to patients
      not meeting the guidelines (interindividual effects; all p < 0.01). Small
      intraindividual effects were found for physical (2.9) and role functioning (4.0)
      and global quality of life (2.1), indicating that patients who went from not
      meeting to meeting the guidelines over time improved on these scales (p < 0.05).
      CONCLUSION: There is a substantial positive association between PA and HRQoL,
      which is consistent over time for CRC survivors >2 years since diagnosis.
      IMPLICATIONS FOR CANCER SURVIVORS: Our results underline the importance to focus
      upon training in survivorship care and strategies to get inactive cancer
      survivors physically active.

PMID- 25573725
TI  - Primary and secondary thrombocytosis induced by exercise and environmental
      luminosity.
AB  - We investigated the exercise and different environmental luminosities effects on
      blood platelets count in order to identify primary and secondary thrombocytosis,
      respectively. BACKGROUND: Platelets alteration has been associated with important
      pathological events, such as neurodegenerative diseases, and the count of these
      cells in bloodstream is influenced by several effects, including physical and
      chemical. Owing the difficulty to study the aetiology of thrombocytosis in human
      models, we employed acute and chronic free drug interventions in order to
      identify these two types of this important disease in laboratory animals.
      METHODS: Forty rats were exposed to standard (SI) or experimental (EI)
      illumination from 45 days-old. Both groups were exposed to 12 h daylight (2700 K;
      565-590 nm; < 60 lux; from 06:00 h to 18:00 h). During dark period SI animals
      were kept in total darkness while EI remained under red light (> 600 nm, < 15
      lux). At 92 days-old, exercised animals were submitted to an acute bout of
      swimming at individualized intensity and control animals remained at rest.
      RESULTS: Blood samples were collected immediately after the exercise for
      platelets count, which were among 849000 +/- 115817 and 1085600 +/- 177089/mm3 of
      blood. Exercise (F = 6.91; p = 0.01) and EI (F = 6.66; p = 0.01) increased
      platelets count, showing no interaction between effects (F = 0.01; p = 0.89).
      CONCLUSION: Primary thrombocytosis was detected owing an acute exercise and the
      secondary thrombocytosis due to the constant red light during dark period,
      without any pharmacological interventions and strongly respecting the ethical
      aspects, enabling future studies on aetiology of thrombocytosis through this
      model (Fig. 2, Ref. 35).

PMID- 25573726
TI  - Chemopreventive potential of alpha lipoic acid in the treatment of colon and
      cervix cancer cell lines.
AB  - OBJECTIVES: The nuclear factor kappaB regulates the expression of genes involved
      in many processes that play a key role in the development and progression of
      cancer. The aim of this study was to examine the influence of the alpha lipoic
      acid in the chemoprevention of colon and cervix carcinoma in vitro. BACKGROUND:
      In recent years, special attention has been paid to the potential chemopreventive
      properties of antioxidants. There are no published data on the impact of alpha
      lipoc acid of chemoprevention of cervix and colon cancer. METHODS: We examined
      the effect of alpha lipoic acid alone or in combination with cisplatin and 5
      fluorouracil on proliferation of the two cell lines, HeLa (human cervical
      carcinoma cells) and Caco-2 (human colon cancer cells) by MTT test. The
      measurement of the level of transcription factor NF-kappaB was also performed in
      the cells of both cell lines. RESULTS: At least one of the mechanisms of the
      antiproliferative and/or cytotoxic effect of alpha lipoic acid on Caco-2 and HeLa
      cells at high concentrations, the transcription factor NF-kappaB, may be
      involved, as well as the products of transcription of genes that are under its
      control. CONCLUSION: The alpha lipoic acid has proven to be a promising candidate
      in the combat arena against cancer (Tab. 4, Ref. 31).

PMID- 25573727
TI  - Time to exhaustion at anaerobic threshold in swimming rats: metabolic
      investigation.
AB  - The purpose of this study was to determine the time to exhaustion (tlim) for
      swimming exercise at anaerobic threshold (AT) intensity in rats and to analyze
      metabolic consequences on serum and tissues levels. Eighteen rats were divided in
      control (CG) and exercised (EG) groups, being the former submitted to tlim. We
      analyzed the glycogen content of liver and ten skeletal muscles, as well as serum
      parameters. Parametric statistic was used with significance level at p < 0.05.
      The tlim, which was correspondent to 114.37 +/- 36.23 min, promoted significant
      decrease in blood glucose (42.99 %; p < 0.01) and an increase in free fatty acids
      (167.12 %; p < 0.01) when EG was compared to CG. We did not find differences in
      albumin, total protein uric acid and creatinine between groups. The proposed
      exercise at individualized AT intensity promoted severe glycogen depletion for
      all tissues (mean of 78.05 % for all muscles and 89 % for liver). With
      substantial control of exercise intensity, our study establishes a useful rodent
      model that can be further explored, contributing to the advancement on knowledge
      and better understanding of exhaustion mechanisms.

PMID- 25573728
TI  - Favourable effect of Eugenol on liver histology in acute cholestasis in rats
      after bile duct ligation.
AB  - BACKGROUND: Eugenol an essential oil found in clove was previously shown to have
      some anti-inflammatory properties. It also was shown to be linked to
      hepatoprotective effect. In this regard, we aimed to reveal the effect of eugenol
      on cholestatic liver disease. METHOD: Cholestatic liver disease model was
      established in 20 rats via bile duct ligation. Eugenol was administered and
      cytokine levels and liver histology after sacrifice were evaluated. RESULTS:
      Biliary ductular proliferation and neutropil infiltration were lower in eugenol
      administered rats. CONCLUSION: Eugenol has a promising effect on liver histology
      in cholestatic liver disease (Tab. 1, Fig. 2, Ref. 16).

PMID- 25573729
TI  - Experimental research on end-to-side anastomosis of peripheral nerves and effect
      of FK506 on end-to-side anastomosis.
AB  - OBJECTIVE: To study the effects of end-to-side anastomosis of initially-denatured
      nerves at different times. METHOD: 60 male Wistar albino rats were used to
      fabricate animal models for the experiment on end-to-side anastomosis of
      peripheral nerves and 50 female Wistar albino rats were used to fabricate animal
      models for the experiment on the effect of FK506 on end-to-side anastomosis.
      Bilateral common peroneal nerve, tibialis anterior muscle electrophysiological
      and histological examinations, tibialis anterior muscle wet muscle weight
      determination, and motor end plate examination were performed 3 months after
      operation. RESULTS: All recovery rates of action potential, single muscle
      contraction force and tetanic contraction force of the FK506 experimental group
      are significantly higher than those of the control group and the sectional area
      of muscle fiber is also higher than that of the control group of normal saline.
      CONCLUSION: The best time for end-to-side anastomosis of nerves should be
      controlled within 2 weeks and the effect of end-to-side anastomosis of nerves
      will gradually become unsatisfactory. FK506 plays a role in promoting functional
      rehabilitation following nerve end-to-side anastomosis (Tab. 7, Fig. 4, Ref. 31).

PMID- 25573731
TI  - Correlations of ADHD symptoms with neurometabolites measured by 1H magnetic
      resonance spectroscopy.
AB  - OBJECTIVES: Despite the number of studies on neurometabolite changes in ADHD
      (Attention deficit/hyperactivity disorder), there is lack of evidence on
      neurometabolite associations with ADHD symptoms. BACKGROUND: We aimed to find the
      correlations of neurometabolites with ADHD symptoms. METHODS: Twenty ADHD
      children were examined by means of 1H-MRS. The spectra were taken from
      dorsolateral prefrontal cortex (DLPFC) and white matter behind DLPFC,
      bilaterally. Neurometabolites were correlated with ADHD-RS-IV (ADHD-Rating Scales
      IV), CPRS (Conners Parent rating Scale) and DPREMB (Daily Parent Rating of
      Evening and Morning Behavior) scores. RESULTS: NAA/Cr (N
      acetylaspartate/creatine) in the right DLPFC positively correlated with CPRS
      subscale IV learning problems and negatively correlated in the left white matter
      with DPREMB morning behavior subscale and ADHD-RS-IV score. Glx/Cr (glutamate +
      glutamine/creatine) positively correlated in the right white matter with ADHD-RS
      IV and negatively correlated in the left white matter with DPREMB morning
      behavior subscale score. Cho/Cr (choline/creatine) in the left white matter
      negatively correlated with DPREMB morning behavior subscale and ADHD-RS-IV score.
      CONCLUSION: ADHD symptoms could result from different activities of the left- and
      right-hemisphere prefrontal circuits. In consequence to impulses to novel task
      searching the increased right prefrontal circuit activity could be mediated by
      different motivational control (Fig. 9, Ref. 73).

PMID- 25573730
TI  - Effects of amlodipine administration and withdrawal on rat pituitary
      gonadotropins.
AB  - OBJECTIVE: The study was aimed to observe the effect of amlodipine on rat
      pituitary gonadotropins after amlodipine administration and withdrawal. METHODS:
      It was an experimental study done at Army Medical College, National University of
      Sciences and Technology, Islamabad, Pakistan from 2009-2010. Sixty adult male
      rats were divided into groups A and B. Each group was further subdivided into two
      subgroups of 15 rats each; A1 (control), A2 (control recovery), B1 (amlodipine
      treated) and B2 (amlodipine recovery). Amlodipine, 0.04 mg/kg body weight daily
      for fifty days was given by means of gavage to groups B1 and B2. Groups A1 and A2
      were given vehicle (0.5 ml distilled water). After 50 days, rats in groups A1 and
      B1 were sacrificed and their serum LH and FSH levels were measured by Enzyme
      Immunoassay method. Vehicle and amlodipine were withdrawn in groups A2 and B2,
      respectively, and the rats were left for recovery to take place for another fifty
      days. The above procedure was adopted for the measurement of LH and FSH levels in
      the recovered rats. RESULTS: Amlodipine administration for 50 days resulted in a
      significant rise in serum LH (p < 0.01) whereas serum FSH remained unchanged (p
      >= 0.05). Serum LH in amlodipine-treated rats returned to normal after amlodipine
      withdrawal (p >= 0.05). CONCLUSION: Amlodipine causes a reversible increase in
      serum LH but it has no effect on serum FSH (Fig. 2, Ref. 17).

PMID- 25573733
TI  - Primary hyperparathyreosis: is concordant sonography and scintigraphy really so
      important?
AB  - BACKGROUND: In primary hyperparathyreosis, US and scintigraphy are the most usual
      preoperative localization methods for detection of parathyroid adenomas or
      hyperplasia. RESULTS: 88 (80 female) patients were detected. Unilateral neck
      exploration was performed in 43 patients (48.9 %) and bilateral exploration in 45
      patients (51.1 %). The cure rate was 97.6 %. None case of parathyroid hyperplasia
      was detected, there were 2 cases of duplex adenoma. For left/right and quadrant
      localization, sensitivity of US was 71.05 % and 55.07 %, of scintigraphy 95.77 %
      and 88.71 %, and in concordant imaging 97.67 % and 96.77 %. Analogically, PPV
      was: US 91.53 % and 76.00 %, scintigraphy 87.18 % and 74.32 %, concordant imaging
      93.33 %and 81.08 %. Only US sensitivity was significantly lower, all other
      differences showed no statistical significance. CONCLUSION: Our data showed low
      sensitivity but a high positive predictive value of ultrasonography and a high
      diagnostic value of scintigraphy. Sensitivity and the positive predictive value
      of concordant localization showed no significant difference, compared to
      scintigraphy. The routine need for concordance for parathyroid adenoma
      localization appears dubious, however, its value for prediction of multiglandular
      disease remains important for protocols that do not apply peroperative
      localization (Tab. 2, Ref. 35).

PMID- 25573732
TI  - Suboptimal use of gastroprotective medication in elderly antiplatelet users.
AB  - BACKGROUND: Use of acetylsalicylic acid (ASA) or thienopyridines in monotherapy
      or combination of both drugs is associated with increased risk of
      gastrointestinal (GI) bleeding. The administration of drugs inhibiting gastric
      acid production represents an effective way to avoid GI disorders associated with
      antiplatelet therapy. OBJECTIVES: The aim of our study was to evaluate the use of
      gastroprotective medication in elderly antiplatelet users in relation to risk
      factors for GI bleeding. METHODS: Patients (n = 428) aged >= 65 years who were
      prescribed low dose ASA or clopidogrel in monotherapy or combination at hospital
      discharge were enrolled in the study. RESULTS: Only 39.7 % of patients with 2 or
      more risk factors for GI bleeding were prescribed gastroprotective medication at
      hospital discharge. The probability of elderly antiplatelet drug user for
      prescription of gastroprotective medication was improved with following risk
      factors: age >= 85 years (OR = 2.99); history of peptic ulcer disease/ GI
      bleeding (OR = 15.79); other GI disorders (OR = 15.48); concomitant therapy with
      drugs increasing the risk of GI bleeding - systemic corticosteroids (OR = 29.03)
      and NSAIDs (OR = 4.79). CONCLUSION: Results of our study indicate the necessity
      to increase the awareness of GI bleeding risk in long-term antiplatelet users
      among prescribing physicians.

PMID- 25573734
TI  - Individual goal-directed intraoperative fluid management of initially hypovolemic
      patients for elective major urological surgery.
AB  - BACKGROUND: The impact of different approaches to fluid management during
      intraoperative volume resuscitation in patients undergoing major elective surgery
      is poorly defined. We compared volume effectiveness of crystalloid and colloid
      substitution aimed to maintain the cardiac index (CI) between 2.6 and 3.8
      l/min/m(2) as measured by transesophageal Doppler (TED). METHODS: A total of 115
      urological patients were enrolled in the prospective randomized trial and then
      randomized into 2 groups, one with volume therapy based on crystalloids (n = 57)
      and the other with colloids (n = 58). A TED probe was inserted and then
      hemodynamic optimization (therapy with Ringer's solution or hydroxyethyl starch 6
      % 130/0.4 and administration of vasoactive drugs) was started according to TED
      variables to maintain the CI between 2.6 and 3.8 l/min/m(2). RESULTS: We observed
      high incidence of CI < 2.6 l/min/m(2) after induction of anesthesia (75 %) in
      both groups. There were no significant differences in demographic
      characteristics, ASA classification, length of surgery, estimated blood loss and
      the CI during surgery. To maintain the CI within the requested interval,
      significantly different amounts of crystalloids were needed as compared to
      colloid (median: 5000 ml vs 1500 ml). In the CRY group, more patients were
      treated by vasodilatators (40.4 vs 20.7 %). CONCLUSIONS: The study confirmed that
      crystalloids and colloids are effective in correcting flow-related perfusion
      abnormalities. The significant difference between volumes of crystalloids and
      colloids proved their different characteristics such as unequal distribution
      between compartments. The expansion of therapeutic algorithm by using vasoactive
      drugs allows us to avoid adverse events resulting from fluid overload (Tab. 1,
      Fig. 5, Ref. 35).

PMID- 25573736
TI  - Merckel cell carcinoma of the skin treated with somatostatin analogue and mTOR
      inhibitor exhausted after primary surgery, adjuvant radiotherapy and palliative
      chemotherapy.
AB  - Merkel cell carcinoma is a highly aggressive neuroendocrine skin tumor. This type
      of tumor is primarily based on Merkel cells located in the basal layer of the
      epidermis. The tumor occurs predominantly in elderly individuals (average age 69
      years) and has a strong tendency to local recurrence and locoregional metastasis.
      Diagnosis of the tumor is based on histological and immunohistochemical
      examination. The therapy is radical surgery followed by adjuvant radiotherapy to
      the site of the primary tumor and regional lymph nodes. The authors describe a
      case report of Merkel cell carcinoma of the skin treated with somatostatin
      analogue and mTOR inhibitor exhausted after primary surgery and adjuvant
      radiotherapy and paliative chemotherapy (Fig. 2, Ref. 17).

PMID- 25573735
TI  - Laparoscopic versus open appendectomy in treatment of acute appendicitis.
AB  - INTRODUCTION: The authors present the results of a retrospective study comparing
      the laparoscopic and open procedures of appendectomy for the diagnosis of acute
      appendicitis.Material and methods. Retrospective analysis of the results of both
      methods on a set of 161 patients in period 2006-2010. RESULTS: Regarding the
      intraabdominal complications and hospitalization periods, results confirm the
      equivalence of both methods. A significantly lower incidence of wound
      complications as well as shorter hospital stay were experienced in the
      laparoscopy-treated group of patients. CONCLUSION: Based on the results of this
      study, the laparotomic appendectomy would be reserved for appendicitis with
      diffuse peritonitis. The laparoscopy is positively preferred in obese patients
      (Tab. 3, Ref. 16).

PMID- 25573737
TI  - The thyroid cancer and Basedow's disease.

PMID- 25573738
TI  - Functional relationships for the estimation of van Genuchten parameter values in
      landfill processes models.
AB  - Numerical models of landfill processes need to be able to estimate the capillary
      pressure and relative permeability of waste as a function of moisture content
      using analytical equations such as the van Genuchten equations. The paper
      identifies the range of van Genuchten parameter values for use in models and
      proposes a formulaic relationship between these parameter values and saturated
      moisture content. The concept of porous material, its behaviour under unsaturated
      conditions and Mualem's integral transform equation that estimates relative
      permeability from capillary pressure are reviewed. The application of the
      algebraic form of the capillary pressure function proposed by van Genuchten and
      its application using Mualem's transform to obtain the van Genuchten algebraic
      functions for relative permeability are discussed. Functional relationships are
      identified between saturated moisture content and the van Genuchten parameters
      using a database of results from other sources. These relationships may be used
      in numerical modelling of unsaturated flow in landfilled waste where the
      saturated moisture content varies significantly as the result of compression,
      settlement and degradation. A 2D numerical model simulation of leachate
      recirculation is used to investigate the sensitivity of the simulation to the
      introduction of these functional relationships. It is found that the transient
      liquid and gas flows across the model boundaries appear to be insensitive to
      whether or not the functions are incorporated into the model algorithm. However
      it is observed that using the relationships does have some impact on the
      distribution of the degree of saturation throughout the model and on the
      transient behaviour of the way in which the recirculation recharges the waste.
      However it is not thought that this impact would be sufficient to influence the
      design of a leachate recirculation system. 

PMID- 25573739
TI  - Life cycle assessment and residue leaching: the importance of parameter, scenario
      and leaching data selection.
AB  - Residues from industrial processes and waste management systems (WMSs) have been
      increasingly reutilised, leading to landfilling rate reductions and the
      optimisation of mineral resource utilisation in society. Life cycle assessment
      (LCA) is a holistic methodology allowing for the analysis of systems and products
      and can be applied to waste management systems to identify environmental benefits
      and critical aspects thereof. From an LCA perspective, residue utilisation
      provides benefits such as avoiding the production and depletion of primary
      materials, but it can lead to environmental burdens, due to the potential
      leaching of toxic substances. In waste LCA studies where residue utilisation is
      included, leaching has generally been neglected. In this study, municipal solid
      waste incineration bottom ash (MSWI BA) was used as a case study into three LCA
      scenarios having different system boundaries. The importance of data quality and
      parameter selection in the overall LCA results was evaluated, and an innovative
      method to assess metal transport into the environment was applied, in order to
      determine emissions to the soil and water compartments for use in an LCA. It was
      found that toxic impacts as a result of leaching were dominant in systems
      including only MSWI BA utilisation, while leaching appeared negligible in larger
      scenarios including the entire waste system. However, leaching could not be
      disregarded a priori, due to large uncertainties characterising other activities
      in the scenario (e.g. electricity production). Based on the analysis of relevant
      parameters relative to leaching, and on general results of the study,
      recommendations are provided regarding the use of leaching data in LCA studies. 

PMID- 25573741
TI  - Prognostic factors in operable breast cancer treated with neoadjuvant
      chemotherapy: towards a quantification of residual disease.
AB  - OBJECTIVE: Neoadjuvant chemotherapy (NACT) allows for a more frequent use of
      breast-conservative surgery; it is also an in vivo model of individual tumor
      sensitivity which permits to determine new prognostic factors to personalize the
      therapeutic approach. METHODS: Between 2000 and 2012, 318 patients with primary
      invasive breast cancer were treated with a median of 6 cycles of NACT; they
      received either an anthracycline-based FEC 100 protocol (31.1%), or
      anthracyclines + taxanes (53.5%), with trastuzumab if indicated (15.4%). RESULTS:
      After a median follow-up of 44.2 months, the pathological complete response rate
      according to the classification of Chevallier et al. [Am J Clin Oncol 1993;16:223
      228] was 19.3%, and overall (OS) and disease-free survival (DFS) at 10 years were
      60.2 and 69.6%, respectively. Univariate analyses demonstrated that the Residual
      Disease in Breast and Nodes (RDBN) index was the most significant prognostic
      factor for OS (p = 0.0082) and DFS (p = 0.0022), and multivariate analyses mainly
      revealed that the residual tumor size, residual involved node number and post
      chemotherapy Scarff-Bloom-Richardson (SBR) grading were the most significant
      prognostic factors. CONCLUSIONS: In a cohort of patients who were all
      homogeneously treated with some of the most common drugs for breast cancer, we
      demonstrate that NACT may provide additional prognostic factors and confirm the
      RDBN index. As this index allows for the prediction of survival with different
      breast cancer subtypes, we suggest that it should be calculated routinely to help
      clinicians to select patients who need adjuvant treatments.

PMID- 25573742
TI  - Inter and intra island introgression in a wolf spider radiation from the
      Galapagos, and its implications for parallel evolution.
AB  - Parallel radiations within island systems are often assumed to follow a simple
      scenario in which single colonization events are followed by in situ adaptive
      divergence. However, subsequent gene exchange after the initial colonization and
      during the divergence process might have important evolutionary impacts on
      species radiations. Gene exchange among ecologically similar species from
      different islands may lead to introgression of adaptive genetic variation and
      influence the parallel divergence process. In this study, we estimate levels of
      gene exchange within a wolf spider radiation of the genus Hogna Simon, 1885, from
      the Galapagos, wherein habitat specialization into 'high elevation' and 'coastal
      dry' species apparently evolved repeatedly on two islands. By using a multilocus
      approach we show that low levels of inter-island and relatively higher levels of
      intra island introgression shaped genetic variation in this species complex.
      Using these estimates, we demonstrate by means of a coalescence simulation that
      under these inter- and intra-island migration rates parallel evolution most
      likely evolves by introgression of adaptive alleles among islands, rather than
      through independent mutations despite the close genetic relationship of species
      within islands. As species phylogenies within radiations are frequently used to
      infer the divergence pattern, even relatively low levels of interspecific gene
      flow should not be neglected when interpreting parallel trait evolution. 

PMID- 25573740
TI  - Lymphocyte roles in metabolic dysfunction: of men and mice.
AB  - Type 2 diabetes (T2D) is a metabolic disease associated with obesity-related
      insulin resistance (IR) and chronic inflammation. Animal studies indicate that IR
      can be caused and/or exacerbated by systemic and/or tissue-specific alterations
      in lymphocyte differentiation and function. Human studies also indicate that
      obesity-associated inflammation promotes IR. Nevertheless, clinical trials with
      anti-inflammatory therapies have yielded modest impacts on established T2D.
      Unlike mouse models, where obesity is predominantly associated with IR, 20-25% of
      obese humans are metabolically healthy with high insulin sensitivity. The
      uncoupling of obesity from IR in humans but not in animal models advocates for a
      more comprehensive understanding of mediators and mechanisms of human obesity
      promoted IR, and better integration of knowledge from human studies into animal
      experiments to efficiently pursue T2D prevention and treatment. 

PMID- 25573743
TI  - Smoke-free policy implementation: theoretical and practical considerations.
AB  - Secondhand smoke exposure is a major public health issue, increasing the risk of
      cardiovascular and respiratory diseases and cancer. Although best practices for
      adopting smoke-free policy are well understood, there is limited research on the
      effective implementation of smoke-free policy. This article presents theoretical
      and practical considerations for smoke-free policy implementation in three
      Kentucky communities guided by the Institutional Analysis and Development (IAD)
      Framework. Although both Danville and Lexington-Fayette County, Kentucky have
      comprehensive smoke-free policies, Danville had more effective implementation, as
      well as better outcomes. Further study is needed to understand the critical
      elements of smoke-free policy implementation and their association with
      population outcomes. The IAD is a promising model to guide the study of both
      policy adoption and implementation. 

PMID- 25573744
TI  - Characterization of the host response to pichinde virus infection in the Syrian
      golden hamster by species-specific kinome analysis.
AB  - The Syrian golden hamster has been increasingly used to study viral hemorrhagic
      fever (VHF) pathogenesis and countermeasure efficacy. As VHFs are a global health
      concern, well-characterized animal models are essential for both the development
      of therapeutics and vaccines as well as for increasing our understanding of the
      molecular events that underlie viral pathogenesis. However, the paucity of
      reagents or platforms that are available for studying hamsters at a molecular
      level limits the ability to extract biological information from this important
      animal model. As such, there is a need to develop platforms/technologies for
      characterizing host responses of hamsters at a molecular level. To this end, we
      developed hamster-specific kinome peptide arrays to characterize the molecular
      host response of the Syrian golden hamster. After validating the functionality of
      the arrays using immune agonists of defined signaling mechanisms
      (lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-alpha), we
      characterized the host response in a hamster model of VHF based on Pichinde virus
      (PICV(1)) infection by performing temporal kinome analysis of lung tissue. Our
      analysis revealed key roles for vascular endothelial growth factor (VEGF),
      interleukin (IL) responses, nuclear factor kappa-light-chain-enhancer of
      activated B cells (NF-kappaB) signaling, and Toll-like receptor (TLR) signaling
      in the response to PICV infection. These findings were validated through
      phosphorylation-specific Western blot analysis. Overall, we have demonstrated
      that hamster-specific kinome arrays are a robust tool for characterizing the
      species-specific molecular host response in a VHF model. Further, our results
      provide key insights into the hamster host response to PICV infection and will
      inform future studies with high-consequence VHF pathogens. 

PMID- 25573745
TI  - Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO)
      controls endothelial cell (EC) permeability.
AB  - Endothelial cells (ECs) play a key role to maintain the functionality of blood
      vessels. Altered EC permeability causes severe impairment in vessel stability and
      is a hallmark of pathologies such as cancer and thrombosis. Integrating label
      free quantitative proteomics data into genome-wide metabolic modeling, we built
      up a model that predicts the metabolic fluxes in ECs when cultured on a
      tridimensional matrix and organize into a vascular-like network. We discovered
      how fatty acid oxidation increases when ECs are assembled into a fully formed
      network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate
      limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen
      consumption, which are restored by replenishing the tricarboxylic acid cycle.
      Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition
      pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases
      intracellular calcium oscillations. Finally, inhibiting CPT1A induces
      hyperpermeability in vitro and leakage of blood vessel in vivo, which were
      restored blocking calcium influx or replenishing the tricarboxylic acid cycle.
      Fatty acid oxidation emerges as central regulator of endothelial functions and
      blood vessel stability and druggable pathway to control pathological vascular
      permeability. 

PMID- 25573747
TI  - Aortic dissection in children and adolescents with Turner syndrome: risk factors
      and management recommendations.
AB  - There is a general lack of awareness of the risk of aortic dissection in Turner
      syndrome (TS) from both patients with TS and their physicians. Patients often
      ignore symptoms for up to 24 h before seeking medical advice, significantly
      increasing their risk of death. A clinical profile of those at risk of dissection
      is emerging and includes the presence of congenital heart defects, aortic
      dilatation and hypertension. MRI has revolutionised the visualisation of
      cardiovascular anatomy in TS but remains underutilised, especially in children
      and adolescents, and there is currently little guidance on blood pressure (BP)
      assessment or hypertension management. Children and adolescents with TS at risk
      of dissection could be easily identified by timely imaging and BP assessment.
      This would allow medical management or surgical intervention to be put in place
      to reduce the risk of this major, and often fatal, complication. Since guidance
      is lacking, we have reviewed the literature on the risk factors for dissection in
      TS during childhood and adolescence, and make recommendations on the assessment
      and management of these patients.

PMID- 25573748
TI  - Empathetic attitudes of undergraduate paramedic and nursing students towards four
      medical conditions: a three-year longitudinal study.
AB  - INTRODUCTION: In the healthcare context empathy is the cognitive ability to
      understand a patient's perspectives and experiences and to convey that
      understanding back to the patient. Some medical conditions are frequently
      stigmatised or otherwise detrimentally stereotyped with patients often describing
      healthcare practitioners as intolerant, prejudiced and discriminatory.
      OBJECTIVES: The purpose of this study was to find how a group of paramedic
      students and nursing/paramedic double-degree students regard these types of
      patients and to note any changes that may occur as those students continued
      through their education. METHODS: The 11-questions, 6-point Likert scale version
      of the Medical Condition Regard Scale was used in this prospective cross
      sectional longitudinal study. This study included paramedic students enrolled in
      first, second, third and fourth year of an undergraduate paramedic or
      paramedic/nursing program from Monash University. RESULTS: A total of 554
      students participated. Statistically significant differences were found between
      double-degree and single-degree students (p<0.0001), year of course (p<0.0001)
      and gender (p=0.02) for patients presenting with substance abuse. Similar results
      were found for patients with intellectual disability and attempted suicide. No
      statistically significant results were found for acute mental illness.
      CONCLUSIONS: This study has demonstrated significant differences in empathy
      between paramedic and nursing/paramedic double-degree students in regard to
      patients with these complex medical conditions. Paramedic/nursing students
      generally showed a positive change in empathy towards these complex patients by
      their third year of study; however, they also showed some alarming drops in
      empathy between second and third year.

PMID- 25573746
TI  - Tissue specific dysregulated protein subnetworks in type 2 diabetic bladder
      urothelium and detrusor muscle.
AB  - Diabetes mellitus is well known to cause bladder dysfunction; however, the
      molecular mechanisms governing this process and the effects on individual tissue
      elements within the bladder are poorly understood, particularly in type 2
      diabetes. A shotgun proteomics approach was applied to identify proteins
      differentially expressed between type 2 diabetic (TallyHo) and control (SWR/J)
      mice in the bladder smooth muscle and urothelium, separately. We were able to
      identify 1760 nonredundant proteins from the detrusor smooth muscle and 3169
      nonredundant proteins from urothelium. Pathway and network analysis of
      significantly dysregulated proteins was conducted to investigate the molecular
      processes associated with diabetes. This pinpointed ERK1/2 signaling as a key
      regulatory node in the diabetes-induced pathophysiology for both tissue types.
      The detrusor muscle samples showed diabetes-induced increased tissue remodeling
      type events such as Actin Cytoskeleton Signaling and Signaling by Rho Family
      GTPases. The diabetic urothelium samples exhibited oxidative stress responses, as
      seen in the suppression of protein expression for key players in the NRF2
      Mediated Oxidative Stress Response pathway. These results suggest that diabetes
      induced elevated inflammatory responses, oxidative stress, and tissue remodeling
      are involved in the development of tissue specific diabetic bladder dysfunctions.
      Validation of signaling dysregulation as a function of diabetes was performed
      using Western blotting. These data illustrated changes in ERK1/2 phosphorylation
      as a function of diabetes, with significant decreases in diabetes-associated
      phosphorylation in urothelium, but the opposite effect in detrusor muscle. These
      data highlight the importance of understanding tissue specific effects of disease
      process in understanding pathophysiology in complex disease and pave the way for
      future studies to better understand important molecular targets in reversing
      bladder dysfunction. 

PMID- 25573749
TI  - Extremophiles survival to simulated space conditions: an astrobiology model
      study.
AB  - In this work we investigated the ability of four extremophilic bacteria from
      Archaea and Bacteria domains to resist to space environment by exposing them to
      extreme conditions of temperature, UV radiation, desiccation coupled to low
      pressure generated in a Mars' conditions simulator. All the investigated
      extremophilic strains (namely Sulfolobus solfataricus, Haloterrigena hispanica,
      Thermotoga neapolitana and Geobacillus thermantarcticus) showed a good resistance
      to the simulation of the temperature variation in the space; on the other hand
      irradiation with UV at 254 nm affected only slightly the growth of H. hispanica,
      G. thermantarcticus and S. solfataricus; finally exposition to Mars simulated
      condition showed that H. hispanica and G. thermantarcticus were resistant to
      desiccation and low pressure. 

PMID- 25573750
TI  - A failed platform: The Citizen Consensus Conference travels to Chile.
AB  - This article starts by reviewing the setbacks that the recent Science and
      Technology Studies literature has identified in the functioning of technologies
      of democracy, the different arrangements that look to enact deliberation on
      technoscientific issues. Putting a focus on the Citizen Consensus Conference, it
      then proposes that several of these setbacks are related to the kind of "work"
      that these technologies are expected to do, identifying two kinds of it:
      performing a laboratory-based experiment and constituting a platform for the
      dissemination of facts. It then applies this framework to study a Citizen
      Consensus Conference carried out in Chile in 2003. After a detailed genealogy of
      the planning, implementation and afterlife of this exercise, the article
      concludes that several of the limitations experienced are derived from a
      "successful outcome" conceived as solely running a neat lab-based experiment,
      arguing for the need to incorporate its functioning as a platform with all the
      associated transformations and messiness.

PMID- 25573751
TI  - Polymorphism of organic cation transporter 2 improves glucose-lowering effect of
      metformin via influencing its pharmacokinetics in Chinese type 2 diabetic
      patients.
AB  - BACKGROUND AND OBJECTIVES: This study aimed to investigate how the organic cation
      transporter 2 nucleotide polymorphism at site 808 (G -> T) affects metformin
      pharmacokinetics and its long-term anti-diabetic effect. METHODS: A total of 220
      newly diagnosed type 2 diabetes patients taking oral metformin were recruited,
      genotyped and then divided into three groups by SLC22A2 genotypes (G/G, G/T,
      T/T). Nine patients in the GG genotype group, five patients in the GT genotype
      group and four patients in the TT genotype group were randomly selected for the
      metformin pharmacokinetic study. A randomized cohort study with 1-year follow-up
      was performed to clarify the metformin pharmacodynamics. RESULTS: After 1 year,
      the decrease in glycosylated hemoglobin (HbA1c) levels in subjects with the
      heterozygous variant genotype (GT) was significantly greater than in those with
      the wild-type homozygote (-2.2 % in GT vs. -1.1 % in GG, P < 0.05) after
      adjustment for baseline HbA1c levels, exercise and diet in each group. There were
      also differences in the pharmacokinetic parameters (95 % confidence interval) of
      metformin between these two groups [area under the concentration-time curve
      (AUC)0-infinity 19.7 (15.7-23.8) vs. 14.3 (11.7-16.9) MUg h/L; renal clearance
      (CLr) 16.8 (8.5-25.0) vs. 34.1 (24.9-43.2) L/h; tubular secretion clearance (CLt)
      8.1 (2.2-18.1) vs. 22.7 (15.5-29.8) L/h; all P < 0.05]. Multivariate analysis
      further revealed that the presence of T alleles and gender were independent
      influencing factors of urine excretion of metformin (P < 0.05). CONCLUSION: As
      well as gender, the glucose-lowering efficiency of metformin can be enhanced by
      SLC22A2 808G > T variants through the delay of its transportation and CLr in
      Chinese type 2 diabetes populations.

PMID- 25573753
TI  - Circadian organization of the rodent retina involves strongly coupled, layer
      specific oscillators.
AB  - Rhythmic physiology is central to retinal function and survival and adapts vision
      to daily light intensity changes. Mammalian retina rhythmically releases
      melatonin when cultured under constant conditions, and the occurrence of clock
      gene [e.g., Period (Per)] expression has been shown for most cellular layers.
      However, contribution of the distinct layers to genesis of circadian rhythms
      within the retina is still debated. To characterize their endogenous oscillatory
      capacity and their communication at the whole-tissue level, we used a vibratome
      based method to isolate individual or paired retina cellular layers from the
      mPer2(Luc) mouse and Per1-luciferase (Per1-Luc) rat, and real-time recorded
      bioluminescence. We report that each layer of the mouse retina harbors a self
      sustained oscillator whose period is significantly longer (~ 26 hours) than in
      whole-retina explants (~ 22.9 hours), indicating that the period is correlated
      with the degree of coupling. Accordingly, the maximal period (~ 29 hours) is
      reached upon complete enzymatic dissociation of the retina. By using
      pharmacological approaches, we demonstrate that connection between retina
      oscillators involves gap junctions but only minor contribution from the main
      retina neurochemicals. Taken together with results from Per1-Luc rats, these data
      show that mammalian retina consists of a network of layer-specific oscillators
      whose period is determined by their connectivity.

PMID- 25573752
TI  - Direct or indirect stimulation of adenosine A2A receptors enhances bone
      regeneration as well as bone morphogenetic protein-2.
AB  - Promoting bone regeneration and repair of bone defects is a need that has not
      been well met to date. We have previously found that adenosine, acting via A2A
      receptors (A2AR) promotes wound healing and inhibits inflammatory osteolysis and
      hypothesized that A2AR might be a novel target to promote bone regeneration.
      Therefore, we determined whether direct A2AR stimulation or increasing endogenous
      adenosine concentrations via purine transport blockade with dipyridamole
      regulates bone formation. We determined whether coverage of a 3 mm trephine
      defect in a mouse skull with a collagen scaffold soaked in saline, bone
      morphogenetic protein-2 (BMP-2; 200 ng), 1 MUM CGS21680 (A2AR agonist, EC50 = 160
      nM), or 1 MUM dipyridamole (EC50 = 32 nM) promoted bone regeneration.
      Microcomputed tomography examination demonstrated that CGS21680 and dipyridamole
      markedly enhanced bone regeneration as well as BMP-2 8 wk after surgery (60 +/-
      2%, 79 +/- 2%, and 75 +/- 1% bone regeneration, respectively, vs. 32 +/- 2% in
      control, P < 0.001). Blockade by a selective A2AR antagonist (ZM241385, 1 MUM) or
      deletion of A2AR abrogated the effect of CGS21680 and dipyridamole on bone
      regeneration. Both CGS21680 and dipyridamole treatment increased alkaline
      phosphatase-positive osteoblasts and diminished tartrate resistance acid
      phosphatase-positive osteoclasts in the defects. In vivo imaging with a
      fluorescent dye for new bone formation revealed a strong fluorescent signal in
      treated animals that was equivalent to BMP-2. In conclusion, stimulation of A2AR
      by specific agonists or by increasing endogenous adenosine levels stimulates new
      bone formation as well as BMP-2 and represents a novel approach to stimulating
      bone regeneration.

PMID- 25573756
TI  - Evidence-based practice implementation: case report of the evolution of a quality
      improvement program in a multicenter physical therapy organization.
AB  - BACKGROUND AND PURPOSE: Our nation's suboptimal health care quality and
      unsustainable costs can be linked to the failure to implement evidence-based
      interventions. Implementation is the bridge between the decision to adopt a
      strategy and its sustained use in practice. The purpose of this case report is
      threefold: (1) to outline the historical implementation of an evidence-based
      quality improvement project, (2) to describe the program's future direction using
      a systems perspective to identify implementation barriers, and (3) to provide
      implications for the profession as it works toward closing the evidence-to
      practice gap. CASE DESCRIPTION: The University of Pittsburgh Medical Center
      (UPMC) Centers for Rehab Services is a large, multicenter physical therapy
      organization. In 2005, they implemented a Low Back Initiative utilizing evidence
      based protocols to guide clinical decision making. OUTCOMES: The initial
      implementation strategy used a multifaceted approach. Formative evaluations were
      used repeatedly to identify barriers to implementation. Barriers may exist
      outside the organization, they can be created internally, they may result from
      personnel, or they may be a direct function of the research evidence. Since the
      program launch, 3 distinct improvement cycles have been utilized to address
      identified implementation barriers. DISCUSSION: Implementation is an iterative
      process requiring evaluation, measurement, and refinement. During this period,
      behavior change is actualized as clinicians become increasingly proficient and
      committed to their use of new evidence. Successfully incorporating evidence into
      routine practice requires a systems perspective to account for the complexity of
      the clinical setting. The value the profession provides can be enhanced by
      improving the implementation of evidence-based strategies. Achieving this outcome
      will require a concerted effort in all areas of the profession. New skills will
      be needed by leaders, researchers, managers, and clinicians.

PMID- 25573757
TI  - The Link Between Physical Activity and Cognitive Dysfunction in Alzheimer
      Disease.
AB  - Alzheimer disease (AD) is a primary cause of cognitive dysfunction in the elderly
      population worldwide. Despite the allocation of enormous amounts of funding and
      resources to studying this brain disorder, there are no effective pharmacological
      treatments for reducing the severity of pathology and restoring cognitive
      function in affected people. Recent reports on the failure of multiple clinical
      trials for AD have highlighted the need to diversify further the search for new
      therapeutic strategies for cognitive dysfunction. Thus, studies detailing the
      neuroprotective effects of physical activity (PA) on the brain in AD were
      reviewed, and mechanisms by which PA might mitigate AD-related cognitive decline
      were explored. A MEDLINE database search was used to generate a list of studies
      conducted between January 2007 and September 2014 (n=394). These studies, along
      with key references, were screened to identify those that assessed the effects of
      PA on AD-related biomarkers and cognitive function. The search was not limited on
      the basis of intensity, frequency, duration, or mode of activity. However,
      studies in which PA was combined with another intervention (eg, diet,
      pharmacotherapeutics, ovariectomy, cognitive training, behavioral therapy), and
      studies not written in English were excluded. Thirty-eight animal and human
      studies met entry criteria. Most of the studies suggested that PA attenuates
      neuropathology and positively affects cognitive function in AD. Although the
      literature lacked sufficient evidence to support precise PA guidelines,
      convergent evidence does suggest that the incorporation of regular PA into daily
      routines mitigates AD-related symptoms, especially when deployed earlier in the
      disease process. Here the protocols used to alter the progression of AD-related
      neuropathology and cognitive decline are highlighted, and the implications for
      physical therapist practice are discussed. 

PMID- 25573755
TI  - Aquaporin-1 retards renal cyst development in polycystic kidney disease by
      inhibition of Wnt signaling.
AB  - Water channel aquaporin-1 (AQP1) is expressed at epithelial cell plasma membranes
      in renal proximal tubules and thin descending limb of Henle. Recently, AQP1 was
      reported to interact with beta-catenin. Here we investigated the relationship
      between AQP1 and Wnt signaling in in vitro and in vivo models of autosomal
      dominant polycystic kidney disease (PKD). AQP1 overexpression decreased beta
      catenin and cyclinD1 expression, suggesting down-regulation of Wnt signaling, and
      coimmunoprecipitation showed AQP1 interaction with beta-catenin, glycogen
      synthase kinase 3beta, LRP6, and Axin1. AQP1 inhibited cyst development and
      promoted branching in matrix-grown MDCK cells. In embryonic kidney cultures, AQP1
      deletion increased cyst development by up to ~ 40%. Kidney size and cyst number
      were significantly greater in AQP1-null PKD mice than in AQP1-expressing PKD
      mice, with the difference mainly attributed to a greater number of proximal
      tubule cysts. Biochemical analysis revealed decreased beta-catenin
      phosphorylation and increased beta-catenin expression in AQP1-null PKD mice,
      suggesting enhanced Wnt signaling. These results implicate AQP1 as a novel
      determinant in renal cyst development that may involve inhibition of Wnt
      signaling by an AQP1-macromolecular signaling complex.

PMID- 25573754
TI  - The clock protein period 2 synchronizes mitotic expansion and decidual
      transformation of human endometrial stromal cells.
AB  - Implantation requires coordinated interactions between the conceptus and
      surrounding decidual cells, but the involvement of clock genes in this process is
      incompletely understood. Circadian oscillations are predicated on transcriptional
      translational feedback loops, which balance the activities of the transcriptional
      activators CLOCK (circadian locomotor output cycles kaput) and brain muscle arnt
      like 1 and repressors encoded by PER (Period) and Cryptochrome genes. We show
      that loss of PER2 expression silences circadian oscillations in decidualizing
      human endometrial stromal cells (HESCs). Down-regulation occurred between 12 and
      24 hours following differentiation and coincided with reduced CLOCK binding to a
      noncanonical E-box enhancer in the PER2 promoter. RNA sequencing revealed that
      premature inhibition of PER2 by small interfering RNA knockdown leads to a
      grossly disorganized decidual response. Gene ontology analysis highlighted a
      preponderance of cell cycle regulators among the 1121 genes perturbed upon PER2
      knockdown. Congruently, PER2 inhibition abrogated mitotic expansion of
      differentiating HESCs by inducing cell cycle block at G2/M. Analysis of 70
      midluteal endometrial biopsies revealed an inverse correlation between PER2
      transcript levels and the number of miscarriages in women suffering reproductive
      failure (Spearman rank test, rho = -0.3260; P = 0.0046). Thus, PER2 synchronizes
      endometrial proliferation with initiation of aperiodic decidual gene expression;
      uncoupling of these events may cause recurrent pregnancy loss.

PMID- 25573758
TI  - Reported characteristics of participants in physical therapy-related clinical
      trials.
AB  - BACKGROUND: The inclusion of sociodemographic and anthropometric variables in
      published clinical trials enables physical therapists to determine the
      applicability of trial results to patients in their clinics. OBJECTIVE: The aim
      of this study was to examine the reporting of participant sociodemographic and
      anthropometric characteristics in published physical therapy-related clinical
      trials. DESIGN: This was a retrospective review of clinical trials from 2 samples
      drawn from literature applicable to physical therapy. METHODS: Two reviewers
      independently extracted data from a random sample of 152 clinical trials from the
      Physiotherapy Evidence Database (PEDro) and a purposive sample of 85 clinical
      trials published in the journal Physical Therapy (PTJ). A database containing the
      occurrence of sociodemographic (age, sex, race/ethnicity, level of education,
      marital status) and anthropometric variables (height, weight, body mass index) in
      each article was created to generate descriptive statistics about both samples.
      RESULTS: Among the sociodemographic variables, at least 90% of articles reported
      the sex and age of trial participants. Additional sociodemographic
      characteristics that were reported in 20% to 26% of articles were participant
      level of education and participant race/ethnicity. The reporting of
      anthropometric data differed between the 2 samples, with body mass index being
      most commonly reported in the PEDro sample (48.0%) and weight being most commonly
      reported in the PTJ sample (38.8%). LIMITATIONS: Articles reviewed were limited
      by year of publication (from 2008 to 2012 for PTJ articles and 2010 for clinical
      trials from PEDro) and to English-language-only literature. CONCLUSIONS: The
      physical therapy literature would benefit from enhanced reporting requirements
      for both sociodemographic and anthropometric data about participants.

PMID- 25573759
TI  - Design and Kinematic Evaluation of a Novel Joint-Specific Play Controller:
      Application for Wrist and Forearm Therapy.
AB  - BACKGROUND: The wrist extensors and flexors are profoundly affected in most
      children with hemiparetic cerebral palsy (CP) and are the major target of
      physical therapists' and occupational therapists' efforts to restore useful hand
      functions. A limitation of any therapeutic or exercise program can be the level
      of the child's engagement or adherence. The proposed approach capitalizes on the
      primary learning avenue for children: toy play. OBJECTIVE: This study aimed to
      develop and evaluate the measurement accuracy of innovative, motion-specific play
      controllers that are engaging rehabilitative devices for enhancing therapy and
      promoting neural plasticity and functional recovery in children with CP. DESIGN:
      Design objectives of the play controller included a cost-effective, home-based
      supplement to physical therapy, the ability to calibrate the controller so that
      play can be accomplished with any active range of motion, and the capability of
      logging play activity and wrist motion over week-long periods. METHODS: Accuracy
      of the play controller in measuring wrist flexion-extension was evaluated in 6
      children who were developing in a typical manner, using optical motion capture of
      the wrist and forearm as the gold standard. RESULTS: The error of the play
      controller was estimated at approximately 5 degrees in both maximum wrist flexion
      and extension. LIMITATIONS: Measurements were taken during a laboratory session,
      with children without CP, and no toy or computer game was interfaced with the
      play controller. Therefore, the potential engagement of the proposed approach for
      therapy remains to be evaluated. CONCLUSIONS: This study presented the concept,
      development, and wrist tracking accuracy of an inexpensive approach to extremity
      therapy that may have a health benefit for children with hemiparesis, and
      potentially for patients of any age with a wide range of extremity neuromotor
      impairments.

PMID- 25573760
TI  - Management of falls in community-dwelling older adults: clinical guidance
      statement from the Academy of Geriatric Physical Therapy of the American Physical
      Therapy Association.
AB  - BACKGROUND: Falls in older adults are a major public health concern due to high
      prevalence, impact on health outcomes and quality of life, and treatment costs.
      Physical therapists can play a major role in reducing fall risk for older adults;
      however, existing clinical practice guidelines (CPGs) related to fall prevention
      and management are not targeted to physical therapists. OBJECTIVE: The purpose of
      this clinical guidance statement (CGS) is to provide recommendations to physical
      therapists to help improve outcomes in the identification and management of fall
      risk in community-dwelling older adults. DESIGN AND METHODS: The Subcommittee on
      Evidence-Based Documents of the Practice Committee of the Academy of Geriatric
      Physical Therapy developed this CGS. Existing CPGs were identified by systematic
      search and critically appraised using the Appraisal of Guidelines, Research, and
      Evaluation in Europe II (AGREE II) tool. Through this process, 3 CPGs were
      recommended for inclusion in the CGS and were synthesized and summarized.
      RESULTS: Screening recommendations include asking all older adults in contact
      with a health care provider whether they have fallen in the previous year or have
      concerns about balance or walking. Follow-up should include screening for balance
      and mobility impairments. Older adults who screen positive should have a targeted
      multifactorial assessment and targeted intervention. The components of this
      assessment and intervention are reviewed in this CGS, and barriers and issues
      related to implementation are discussed. LIMITATIONS: A gap analysis supports the
      need for the development of a physical therapy-specific CPG to provide more
      precise recommendations for screening and assessment measures, exercise
      parameters, and delivery models. CONCLUSION: This CGS provides recommendations to
      assist physical therapists in the identification and management of fall risk in
      older community-dwelling adults.

PMID- 25573761
TI  - How strongly is aerobic capacity correlated with walking speed and distance after
      stroke? Systematic review and meta-analysis.
AB  - BACKGROUND: Restoration of walking capacity, as reflected by walking speed and
      walking distance, is a primary goal after stroke. Peak aerobic capacity (peak
      oxygen consumption [Vo2peak]) is suggested to be correlated with walking capacity
      after stroke. Although the strength of this correlation is unclear, physical
      therapy programs often target walking capacity by means of aerobic training.
      PURPOSE: The purpose of this systematic review was to summarize the available
      evidence on the correlation between Vo2peak and walking capacity. DATA SOURCES:
      The databases MEDLINE, CINAHL, EMBASE, Cochrane Library, and SPORTDiscus were
      searched up to May 2014. STUDY SELECTION: Cross-sectional studies reporting
      correlation coefficients between Vo2peak and walking capacity in stroke were
      included, along with longitudinal studies reporting these correlation
      coefficients at baseline. DATA EXTRACTION: The methodological quality of the
      studies was assessed using a checklist of 27 items for observational research.
      Information on study design, stroke severity and recovery, and assessments and
      outcome of Vo2peak and walking capacity, as well as the reported correlation
      coefficients, were extracted. DATA SYNTHESIS: Thirteen studies involving 454
      participants were included. Meta-analyses showed combined correlation
      coefficients (rm) for Vo2peak and walking speed and for Vo2peak and walking
      distance of .42 (95% credibility interval=.31, .54) and .52 (95% credibility
      interval=.42, .62), respectively. LIMITATIONS: The studies included in the
      present review had small sample sizes and low methodological quality. Clinical
      and methodological diversity challenged the comparability of the included
      studies, despite statistical homogeneity. Relevant data of 3 studies could not be
      retrieved. CONCLUSIONS: The strength of the correlation of Vo2peak with walking
      speed was low and moderate for Vo2peak and walking distance, respectively,
      indicating that other factors, besides Vo2peak, determine walking capacity after
      stroke.

PMID- 25573762
TI  - Implementing treatment frequency and duration guidelines in a hospital-based
      pediatric outpatient setting: administrative case report.
AB  - BACKGROUND AND PURPOSE: Determining treatment frequency and duration of physical
      therapist services is an important component of outpatient pediatric physical
      therapist practice, yet there is little research available to inform these
      decisions. Treatment frequency guidelines (TFG) can assist decision making in
      guiding pediatric physical therapy. The purpose of this project was to examine
      the feasibility and application of implementing TFG in hospital-based pediatric
      outpatient physical therapy. PROJECT DESCRIPTION: Previously developed TFG were
      modified for use in our pediatric outpatient physical therapy department to
      include duration and were referred to as treatment frequency and duration
      guidelines (TFDG). In order to successfully implement the TFDG, there were 2
      phases to the project. In phase 1, the staff were provided the guidelines and
      procedures in a staff meeting and via email using a PowerPoint presentation.
      Phase 2 was initiated due to the poor response of the staff in implementing the
      guidelines in their practice after phase 1. The format was changed to include
      formal re-education via small-group and one-on-one education sessions (phase 2).
      Chart reviews were completed to assess therapists' adherence to using TFDG.
      OUTCOMES: Therapists' adherence to use of TFDG increased following re-education:
      phase 1 (n=225 charts, 31% adherence) and phase 2 (n=197 charts, 90% adherence).
      DISCUSSION: Treatment frequency and duration guidelines may assist in guiding
      frequency and duration decisions in pediatric physical therapy. Education via in
      person meetings may improve adherence among staff.

PMID- 25573763
TI  - Intergenerational influences on the growth of Maya children: The effect of living
      conditions experienced by mothers and maternal grandmothers during their
      childhood.
AB  - OBJECTIVES: To test the hypothesis that living conditions experienced by maternal
      grandmothers (F1 generation) and mothers (F2 generation) during their childhood
      are related to height and leg length (LL: height - sitting height) of their 6-to
      8 year old children (F3 generation). METHODS: From September 2011 to June 2012 we
      obtained height and LL, and calculated z-score values of these measurements for
      109 triads (F1 , F2 , F3 ) who are Maya living in Merida, Yucatan, Mexico.
      Multiple regression models were adjusted to examine the relation of
      anthropometric and intergenerational socioeconomic parameters of F1 (house index
      and family size during childhood) and F2 (paternal job loss during childhood)
      with the z-score values of height and LL of F3 . RESULTS: Children's height and
      LL were positively associated with maternal height and LL. This association was
      relatively stronger in LL. Better categories of grand-maternal house index were
      significantly associated with higher values of height and LL in grandchildren.
      Grand-maternal family size was positively related with LL, but not with height.
      CONCLUSIONS: Our findings partially support the hypothesis that living conditions
      experienced by recent maternal ancestors (F1 and F2 ) during their growth period
      influence the growth of descendants (F3 ). Results suggest that LL is more
      sensitive to intergenerational influences than is total height and that the
      transition from a traditional rural lifestyle to urban conditions results in new
      exposures for risk in human physical growth.

PMID- 25573764
TI  - Clinical features, surgical treatment, and long-term outcome in pediatric
      patients with moyamoya disease in China.
AB  - BACKGROUND: There was few detailed demographic and clinical data about Chinese
      patients with moyamoya disease. Here we describe the clinical features, surgical
      treatment, and long-term outcome of pediatric patients with moyamoya disease at a
      single institution in China. METHODS: Our cohort included 288 pediatric patients
      with moyamoya disease. The demographic and clinical characteristics were obtained
      by retrospective chart review and long-term outcome was evaluated using the
      stroke status. Univariate and multivariate logistic regression analyses were
      performed to determine the risk factors for clinical outcome. The risk of
      subsequent stroke was determined using the Kaplan-Meier method. RESULTS: The
      median age for the onset of symptoms was 8.0 years. The ratio of female to male
      patients was 1:1. Familial occurrence of moyamoya disease was 9.4%. The incidence
      of postoperative complications was 4.2%. Postoperative ischemic events were
      identified as predictors of unfavorable clinical outcome, while older age of
      symptom onset was associated with a favorable clinical outcome. The Kaplan-Meier
      estimate stroke risk was 5% in the first 2 years, and the 5-year-Kaplan-Meier
      risk of stroke was 9% after surgery for all patients treated with surgical
      revascularization. Overall, 86% of patients had an independent life with no
      significant disability. CONCLUSION: This long-term survey demonstrated that most
      surgically treated pediatric patients with MMD maintain good outcomes. Our
      results indicate that an early diagnosis and active intervention before the
      establishment of irreversible hemodynamic change are essential to achieve a
      favorable clinical outcome.

PMID- 25573766
TI  - Perspective. The failure of cholesteryl ester transfer protein inhibitors: is it
      due to increased blood viscosity?

PMID- 25573765
TI  - Ferritin family proteins and their use in bionanotechnology.
AB  - Ferritin family proteins are found in all kingdoms of life and act to store iron
      within a protein cage and to protect the cell from oxidative damage caused by the
      Fenton reaction. The structural and biochemical features of the ferritins have
      been widely exploited in bionanotechnology applications: from the production of
      metal nanoparticles; as templates for semi-conductor production; and as scaffolds
      for vaccine design and drug delivery. In this review we first discuss the
      structural properties of the main ferritin family proteins, and describe how
      their organisation specifies their functions. Second, we describe materials
      science applications of ferritins that rely on their ability to sequester metal
      within their cavities. Finally, we explore the use of ferritin as a container for
      drug delivery and as a scaffold for the production of vaccines. 

PMID- 25573768
TI  - Effects of genetic variants of ADH1B and ALDH2 and social network on continued
      alcohol drinking among young adolescents in Taiwan.
AB  - BACKGROUND: This study aimed (i) to evaluate the effects of genetic variants of
      ADH1B and ALDH2 and social network position on continued alcohol use in early
      adolescence, and (ii) to explore possible moderating role of pubertal development
      on genetic effects. METHODS: The sample comprised 496 children who ever drank
      alcohol before the ages of 10-12. Information pertaining to sociodemographic
      background, pubertal development, parental drinking, alcohol and tobacco use,
      alcohol-metabolizing genes, and nominated best friends was collected in four
      waves of assessment. Polymorphisms of ADH1B (rs1229984) and ALDH2 (rs671) were
      genotyped. The latent class analysis was first used to characterize longitudinal
      alcohol use pattern, followed by the multinomial logistic regression analyses to
      assess its association with genes, pubertal development, and social network.
      RESULTS: Three distinct classes of alcohol users (i.e. ex-drinkers, sporadic
      drinkers, and continued drinkers) were derived from alcohol-experienced children.
      Both alcohol-metabolizing genes appear to have protective effects, yet such
      relationships were only significant for youngsters in pre-to-early pubertal
      stage: the adjusted odds ratio (aOR) of ADH1B fast-genotype for sporadic drinkers
      was 0.46 and that of ALDH2 slow-genotype for both sporadic and continued drinkers
      was 0.47 and 0.42, respectively. Children having the bridge position in their
      peer network were more likely to be sporadic drinkers (aOR=4.15) and continued
      drinkers (aOR=3.16). CONCLUSIONS: Our results illustrate a potential moderating
      effect of pubertal development on the protective influence of alcohol
      metabolizing genes on subsequent alcohol use among alcohol-experienced children
      as well as the independent contribution of early life's social network to their
      alcohol involvement.

PMID- 25573767
TI  - Nonoperative treatment of frozen shoulder: oral glucocorticoids.
AB  - PURPOSE: The aim of this study was to report our results of glucocorticoid
      therapy combined with pregabalin and a home exercise program in patients with
      frozen shoulder. METHODS: Thirty-three patients (seven males, 26 females; mean
      age 52, range 43-71) diagnosed with primary idiopathic frozen shoulder were
      included in the study. Secondary causes and systemic diseases related to frozen
      shoulder were excluded. Administration of 0.5 mg/kg/day methylprednisolone was
      halved each week and ceased at the end of first month. Pregabalin, paracetamol
      and proton pump inhibitor was also included in the treatment. Physical therapy as
      a home program was initiated as the pain subsided. Patients were evaluated using
      the Constant, DASH and ASES scores in the sixth week and first year. Pain was
      evaluated with VAS and range of motion at each visit. RESULTS: Patients were
      followed up for an average period of 21 months (range 12-37). No adverse effect
      related to glucocorticoid therapy was observed during the treatment. The DASH,
      ASES and Constant scores improved significantly in the sixth week and first year
      (p > 0.05). Average range of motion and pain improved significantly every week
      until full recovery (p > 0.05). CONCLUSION: Glucocorticoid therapy combined with
      pregabalin and a home exercise program is an effective treatment in the first
      stage of frozen shoulder.

PMID- 25573770
TI  - A lactose fermentation product produced by Lactococcus lactis subsp. lactis,
      acetate, inhibits the motility of flagellated pathogenic bacteria.
AB  - Many strains of lactic acid bacteria have been used for the production of
      probiotics. Some metabolites produced by lactic acid bacteria impair the
      motilities of pathogenic bacteria. Because bacterial motility is strongly
      associated with virulence, the metabolic activities of lactic acid bacteria are
      effective for suppressing bacterial infections. Here we show that lactose
      fermentation by Lactococcus lactis subsp. lactis inhibits the motility of
      Salmonella enterica serovar Typhimurium. A single-cell tracking and rotation
      assay for a single flagellum showed that the swimming behaviour of Salmonella was
      severely but transiently impaired through disruption of flagellar rotation on
      exposure to media cultivated with Lac. lactis. Using a pH-sensitive fluorescent
      protein, we observed that the intracellular pH of Salmonella was decreased
      because of some fermentation products of Lac. lactis. We identified acetate as
      the lactose fermentation product of Lac. lactis triggering the paralysis of
      Salmonella flagella. The motilities of Pseudomonas, Vibrio and Leptospira strains
      were also severely disrupted by lactose utilization by Lac. lactis. These results
      highlight the potential use of Lac. lactis for preventing infections by multiple
      bacterial species. 

PMID- 25573769
TI  - (p)ppGpp modulates cell size and the initiation of DNA replication in Caulobacter
      crescentus in response to a block in lipid biosynthesis.
AB  - Stress conditions, such as a block in fatty acid synthesis, signal bacterial
      cells to exit the cell cycle. Caulobacter crescentus FabH is a cell-cycle
      regulated beta-ketoacyl-acyl carrier protein synthase that initiates lipid
      biosynthesis and is essential for growth in rich media. To explore how C.
      crescentus responds to a block in lipid biosynthesis, we created a FabH-depletion
      strain. We found that FabH depletion blocks lipid biosynthesis in rich media and
      causes a cell cycle arrest that requires the alarmone (p)ppGpp for adaptation.
      Notably, basal levels of (p)ppGpp coordinate both a reduction in cell volume and
      a block in the over-initiation of DNA replication in response to FabH depletion.
      The gene ctrA encodes a master transcription factor that directly regulates 95
      cell-cycle-controlled genes while also functioning to inhibit the initiation of
      DNA replication. Here, we demonstrate that ctrA transcription is (p)ppGpp
      dependent during fatty acid starvation. CtrA fails to accumulate when FabH is
      depleted in the absence of (p)ppGpp due to a substantial reduction in ctrA
      transcription. The (p)ppGpp-dependent maintenance of ctrA transcription during
      fatty acid starvation initiated from only one of the two ctrA promoters. In the
      absence of (p)ppGpp, the majority of FabH-depleted cells enter a viable but non
      culturable state, with multiple chromosomes, and are unable to recover from the
      miscoordination of cell cycle events. Thus, basal levels of (p)ppGpp facilitate
      C. crescentus' re-entry into the cell cycle after termination of fatty acid
      starvation. 

PMID- 25573772
TI  - Canada's Patented Medicines (Notice of Compliance) Proceedings and Intellectual
      Property.
AB  - Canada's Patent Register is a tool created by the Patented Medicines (Notice of
      Compliance) Regulations to help innovators protect their inventions relating to
      pharmaceuticals. This tool exists at the intersection between the intellectual
      property and drug approval regimes. By listing a patent on the Patent Register,
      an innovator can prevent a generic manufacturer from entering the marketplace
      rather than having to wait for his or her patent to be infringed. This article
      provides information on the requirements for listing a patent on the Patent
      Register and an overview of how the Patent Medicines (Notice of Compliance)
      Regulations affect the drug approval process. 

PMID- 25573771
TI  - A study of the Fenton-mediated oxidation of methylene blue-cucurbit[n]uril
      complexes.
AB  - Cucurbit[n]urils efficiently decreased the Fenton-mediated oxidation of
      encapsulated dyes, providing a mechanism for some control and selectivity over
      the degradation. The encapsulation of methylene blue into cucurbit[7]uril made it
      highly refractory against Fenton oxidation in the dark or under UVA light
      irradiation. However, the oxidation of the encapsulated dye was significantly
      enhanced under visible light irradiation. This behavior was selective for the
      cucurbit[7]uril complex and not for the cucurbit[8]uril complex, which achieved
      the same degree of protection irrespective of the irradiation conditions. This
      different reactivity of the complexes was further discussed in terms of their
      excited state properties. The main mechanism for protection was the seclusion of
      the dye into cucurbit[n]urils as shown by the fact that the non-encapsulated dye
      safranin was protected much less than methylene blue. Additionally,
      cucurbit[n]urils efficiently trapped hydroxyl radicals, which contributed
      significantly to the protection of the dyes from Fenton-mediated oxidation. 

PMID- 25573773
TI  - Tuberculosis treatment and drug regimens.
AB  - Tuberculosis is an airborne infectious disease treated with combination
      therapeutic regimens. Adherence to long-term antituberculosis therapy is crucial
      for maintaining adequate blood drug level. The emergence and spread of drug
      resistant Mycobacterium tuberculosis strains are mainly favored by the inadequate
      medical management of the patients. The therapeutic approach for drug-resistant
      tuberculosis is cumbersome, because of the poor, expensive, less-effective, and
      toxic alternatives to the first-line drugs. New antituberculosis drugs
      (bedaquiline and delamanid) have been recently approved by the health
      authorities, but they cannot represent the definitive solution to the clinical
      management of drug-resistant tuberculosis forms, particularly in intermediate
      economy settings where the prevalence of drug resistance is high (China, India,
      and former Soviet Union countries). New research and development activities are
      urgently needed. Public health policies are required to preserve the new and old
      therapeutic options. 

PMID- 25573775
TI  - Societal impact of bilirubin-induced hearing impairment in resource-limited
      nations.
AB  - Infants with bilirubin-induced neurologic dysfunction (BIND) are characterized by
      several developmental disabilities including auditory impairments. This paper
      explores the societal impact of bilirubin-induced auditory impairments, inclusive
      of hearing impairments and auditory neuropathy spectrum disorders, on these
      infants, their families, and on the community in resource-limited countries (per
      capita income of US$6,000 or less). Auditory impairments have substantial
      emotional, social, and economic impact on the affected infants, their families
      and communities. The burden is exacerbated by widespread poverty, unfavorable
      community attitudes towards disabilities, and lack of requisite health,
      educational, and social services. Curtailing the incidence of avoidable severe
      hyperbilirubinemia through proactive and effective management of infants at risk
      or with severe hyperbilirubinemia is necessary at all levels of healthcare
      delivery. Early detection and intervention for unavoidable auditory impairments
      should be widely promoted to provide improved developmental trajectories for the
      affected infants. 

PMID- 25573774
TI  - Gene Therapy of ABCA4-Associated Diseases.
AB  - The ATP-binding cassette (ABC) transporter gene, ABCA4 (ABCR), was characterized
      in 1997 as the causal gene for autosomal recessive Stargardt disease (STGD1).
      Shortly thereafter several other phenotypes were associated with mutations in
      ABCA4, which now have collectively emerged as the most frequent cause of retinal
      degeneration phenotypes of Mendelian inheritance. ABCA4 functions as an important
      transporter (or "flippase") of vitamin A derivatives in the visual cycle. Several
      ways to alleviate the effects of the defective ABCA4 protein, which cause
      accumulation of 11-cis and all-trans-retinal in photoreceptors and lipofuscin in
      the retinal pigment epithelium, have been proposed. Although ABCA4 has proven to
      be a difficult research target, substantial progress through genetic, functional,
      and translational studies has allowed major advances in therapeutic applications
      for ABCA4-associated pathology, which should be available to patients in the
      (near) future. Here, we summarize the status of the gene therapy-based treatment
      options of ABCA4-associated diseases. 

PMID- 25573776
TI  - Identification of diabetes-related dementia: Longitudinal perfusion SPECT and
      amyloid PET studies.
AB  - AIMS: We attempted to identify a dementia subgroup with characteristics
      associated with diabetes mellitus (DM)-related metabolic abnormalities, referred
      to as diabetes-related dementia, using longitudinal single photon emission
      computed tomography (SPECT) and Pittsburgh compound-B (PiB) positron emission
      tomography (PET). METHODS: We classified 175 patients with clinically diagnosed
      Alzheimer disease (AD) and DM into 4 subgroups based on brain imaging in a 2013
      study. Among them, we investigated follow-up SPECT studies in 29 patients of an
      AD group showing decreased regional cerebral blood flow (rCBF) of the
      parietotemporal lobe on initial SPECT and 18 patients of a diabetes-related
      dementia group showing neither decreased rCBF of the parietotemporal lobe nor
      cerebrovascular disease, which is strongly associated with DM-related factors.
      Eleven of them underwent PiB PET. RESULTS: Follow-up SPECT showed more profound
      rCBF reduction in the parietotemporal lobe and other areas of the AD group,
      whereas follow-up SPECT showed an rCBF reduction in small areas of the
      frontotemporal and limbic lobes of the diabetes-related dementia group. Six of 9
      patients with diabetes-related dementia were negative or equivocal for PiB
      binding. CONCLUSION: A subset of a dementia subgroup with characteristics
      predominantly associated with DM-related factors may underlie a pathophysiology
      different from AD, although these patients were clinically diagnosed as having
      AD. The identification of diabetes-related dementia may be necessary for
      considering an appropriate therapy and prevention in clinical practice.

PMID- 25573777
TI  - Chemical constituents on the aerial parts of Artemisia selengensis and their IL-6
      inhibitory activity.
AB  - Ten compounds, 1',3'-propanediol,2'-amino-1'-(1,3-benzodioxol-5-yl) (1),
      artanomaloide (2), canin (3), eupatilin (4), quercetin-3-O-beta-D-glucoside-7-O
      alpha-L-rhamnoside (5), 1,3-di-O-caffeoylquinic acid (6), isoquercitrin (7),
      pinoresinol-4-O-beta-D-glucoside (8), scopolin (9), and isofraxidin-7-O-beta-D
      glucopyranoside (10) were isolated from the aerial parts of A. selengensis. The
      structures of compounds (1-10) were identified based on 1D and 2D NMR, including
      (1)H-(1)H COSY, HSQC, HMBC and NOESY spectroscopic analyses. Among them, compound
      1 was isolated from this plant for the first time as a naturally occurring
      compound. The inhibitory activity of these isolated compounds against interleukin
      6 (IL-6) production in TNF-alpha stimulated MG-63 cells was also examined. 

PMID- 25573778
TI  - Fused corrole dimers interconvert between nonaromatic and aromatic states through
      two-electron redox reactions.
AB  - A singly linked corrole dimer was synthesized by condensation of a dipyrromethane
      1-carbinol with 1,1,2,2-tetrapyrroethane. Oxidation of the dimer gave doubly
      linked corrole dimers 9 and 10 as the first examples of fused corrole dimers
      involving a meso-meso linkage. Dimers 9 and 10 exhibit characteristic (1)H NMR
      spectra, absorption spectra, excited-state dynamics, and two-photon absorption
      (TPA) values, which indicate the nonaromatic nature of 9 and the aromatic nature
      of 10. Interestingly, 9 is fairly stable despite its unusual 2H-corrole
      structure, which has been ascribed to the presence of two direct connections
      between the individual corrole units.

PMID- 25573780
TI  - Genetic polymorphism in HLA-G 3'UTR 14-bp ins/del and risk of cancer: a meta
      analysis of case-control study.
AB  - Accumulating evidence has suggested that the human leucocyte antigen-G (HLA-G) 14
      bp ins/del polymorphism might be related to cancer susceptibility. However,
      epidemiologic findings have been inconsistent. Therefore, we performed a meta
      analysis of case-control study to derive a more precise estimation of this
      association. Electronic databases were searched to identify all eligible studies
      of HLA-G 14 bp ins/del polymorphism and cancer risk. Odds ratios (ORs) with 95 %
      confidence intervals (CIs) were calculated to evaluate the strength of the
      association in fixed-effects model or random-effects model according to
      heterogeneity. Publication bias, sensitivity analysis and subgroup analyses based
      on cancer type, ethnicity, source of controls and sample size were also
      performed. A total of 14 case-control studies, involving 2,757 cases and 3,972
      controls, were included in the present meta-analysis. The pooled analysis showed
      that there is no significant relationship between the HLA-G 14 bp ins/del
      polymorphism and cancer susceptibility under the genetic models (for the allele
      model del vs. ins: OR 1.13, 95 % CI 1.00-1.27; for the homozygote comparison
      model del/del vs. ins/ins: OR 1.22, 95 % CI 0.95-1.56; for the dominant model
      del/del + ins/del vs. ins/ins: OR 1.15, 95 % CI 0.94-1.42; for recessive model
      del/del vs. ins/del + ins/ins: OR 1.13, 95 % CI 0.96-1.34; respectively).
      Subgroup analyses indicated significant association among breast cancer,
      population based control and the large sample size group in some genetic models.
      Our investigations demonstrate that genotypes for the HLA-G 14 bp ins/del
      polymorphism may be not associated with overall cancer risk. In a subgroup meta
      analysis, however, HLA-G 14-bp ins/del polymorphism might contribute to breast
      cancer susceptibility.

PMID- 25573781
TI  - [Le Fort I osteotomies combined with post-operative bone grafts].
AB  - INTRODUCTION: We present and assess a surgical technique for maxillary auto-bone
      grafting concomitantly with Le Fort I osteotomy. The graft has 2 main objectives:
      to fill in the space between the 2 advanced segments of the maxilla to help bone
      consolidation, and to increase the volume of the malar, para-nasal spaces to
      improve post-operative esthetic results. TECHNICAL NOTE: Bone fragments, removed
      during the Le Fort I osteotomy, are stored and wrapped in a Surgicel((r)) sheet,
      then grafted in the space left by the osteotomy, or on the anterior maxilla in
      the para-nasal area or on the malar bone. One hundred and twenty-three patient
      records, operated from 2007 to 2012, were collected to assess the post-operative
      course retrospectively. The post-operative course was uneventful in 93.5% of
      cases. About 8.4% of patients (7 cases) presented with a persistent post
      operative maxillary edema. 1 patient (1.2%) presented with a sinus infection
      without any determined etiology. The grafts were all osteointegrated at the end
      of follow-up. DISCUSSION: The technique is simple and quickly performed; it
      improves bone healing and cosmetic results, without increasing morbidity or
      surgical time. It is a good alternative to bone grafts from a secondary sample
      site. It can be applied to all Le Fort I osteotomies.

PMID- 25573779
TI  - Host genetic variations in glutathione-S-transferases, superoxide dismutases and
      catalase genes influence susceptibility to malaria infection in an Indian
      population.
AB  - Antioxidant enzymes can contribute to disease susceptibility or determine
      response to therapy in individuals with malaria. Genetic variations due to
      polymorphisms in host genes encoding antioxidant enzymes such as glutathione S
      transferases-theta, mu, pi (GSTT, GSTM, GSTP), superoxide dismutases (SOD) and
      catalase (CAT), may therefore, influence inter-individual response to malaria
      pathology and propensity of infection caused by Plasmodium vivax (Pv) and
      Plasmodium falciparum (Pf). Therefore, using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing, we
      investigated the association of deletions of GSTT1 and GSTM1, single nucleotide
      polymorphisms (SNPs) of GSTP1 (rs1695), SOD1 (rs2234694), SOD2 (rs4880,
      rs1141718), SOD3 (rs2536512) and CAT (rs1001179) in individuals infected with Pf
      (n = 100) and Pv (n = 100) against healthy controls (n = 150). Our data suggest a
      significant role for GSTM1 deletions in complicated Pv (p = 0.0007) malaria with
      ODDs ratio 3.8 [with 95 % confidence interval (CI) 1.9-7.4]. The results also
      indicated that polymorphisms present in GSTP1, SOD1 and CAT genes may be
      associated with malaria susceptibility (p < 0.05), whereas SOD3 polymorphism may
      play a role in malarial resistance (p < 0.05). In addition, we observed
      significant SNP-SNP interactions with synergistic genetic effects in SOD2, SOD3
      and CAT genes for Pv and in SOD2 and SOD3 genes for Pf. In conclusion, our
      results provide convincing evidence for a relationship between polymorphisms in
      host antioxidant enzymes and susceptibility to malaria infection. 

PMID- 25573783
TI  - Ring opening of donor-acceptor cyclopropanes with the azide ion: a tool for
      construction of N-heterocycles.
AB  - A general method for ring opening of various donor-acceptor cyclopropanes with
      the azide ion through an SN 2-like reaction has been developed. This highly
      regioselective and stereospecific process proceeds through nucleophilic attack on
      the more-substituted C2 atom of a cyclopropane with complete inversion of
      configuration at this center. Results of DFT calculations support the SN 2
      mechanism and demonstrate good qualitative correlation between the relative
      experimental reactivity of cyclopropanes and the calculated energy barriers. The
      reaction provides a straightforward approach to a variety of polyfunctional
      azides in up to 91 % yield. The high synthetic utility of these azides and the
      possibilities of their involvement in diversity-oriented synthesis were
      demonstrated by the developed multipath strategy of their transformations into
      five-, six-, and seven-membered N-heterocycles, as well as complex annulated
      compounds, including natural products and medicines such as (-)-nicotine and
      atorvastatin. 

PMID- 25573782
TI  - Modelling the onset of senescence at the G1/S cell cycle checkpoint.
AB  - BACKGROUND: DNA damage (single or double-strand breaks) triggers adapted cellular
      responses. These responses are elicited through signalling pathways, which
      activate cell cycle checkpoints and basically lead to three cellular fates: cycle
      arrest promoting DNA repair, senescence (permanent arrest) or cell death.
      Cellular senescence is known for having a tumour-suppressive function and its
      regulation arouses a growing scientific interest. Here, we advance a qualitative
      model covering DNA damage response pathways, focusing on G1/S checkpoint
      enforcement, supposedly more sensitive to arrest than G2/M checkpoint. RESULTS:
      We define a discrete, logical model encompassing ATM (ataxia telangiectasia
      mutated) and ATR (ATM and Rad3-related) pathways activation upon DNA damage, as
      well as G1/S checkpoint main components. It also includes the stress responsive
      protein p38MAPK (mitogen-activated protein kinase 14) known to be involved in the
      regulation of senescence. The model has four outcomes that convey alternative
      cell fates: proliferation, (transient) cell cycle arrest, apoptosis and
      senescence. Different levels of DNA damage are considered, defined by distinct
      combinations of single and double-strand breaks. Each leads to a single stable
      state denoting the cell fate adopted upon this specific damage. A range of model
      perturbations corresponding to gene loss-of-function or gain-of-function is
      compared to experimental mutations. CONCLUSIONS: As a step towards an integrative
      model of DNA-damage response pathways to better cover the onset of senescence,
      our model focuses on G1/S checkpoint enforcement. This model qualitatively agrees
      with most experimental observations, including experiments involving mutations.
      Furthermore, it provides some predictions.

PMID- 25573784
TI  - Multicenter evaluation of transcatheter aortic valve replacement using either
      SAPIEN XT or CoreValve: Degree of device oversizing by computed-tomography and
      clinical outcomes.
AB  - OBJECTIVE: To analyze the association between computed-tomography-derived degrees
      of device oversizing and clinical outcomes during transcatheter aortic valve
      replacement (TAVR). BACKGROUND: Previous reports suggest that different devices
      reach optimal results with different degrees of device oversizing. Therefore,
      similar sized devices of different types (SAPIEN XT and CoreValve) may be favored
      in different annular ranges and a case considered borderline between two sizes of
      a specific device might be within a favorable range of another. METHODS AND
      RESULTS: A multicenter registry of 615 consecutive transfemoral TAVR procedures
      using either SAPIEN XT or CoreValve was analyzed. A first group of 190 patients
      had annular sizes for which only moderate oversizing degree was feasible (5-20%
      by area or 2.5-9.5% by perimeter). A second group included 178 patients that had
      annulus size for which only large oversizing degree was feasible (20.1-35% by
      area or 9.6-16.2% by perimeter). In the "only large oversizing feasible group"
      there were more annular rupture events in patients treated by SAPIEN XT valve as
      compared to those treated by CoreValve (3.4% vs. 0%, P = 0.04). In the "only
      moderate oversizing feasible group", those treated by CoreValve had more post
      balloon dilatation and 30-day major stroke in comparison with those treated by
      SAPIEN XT (16.1% vs. 7.7%, P = 0.04 and 8% vs. 1.3%, P = 0.02, respectively).
      CONCLUSIONS: Optimal clinical performance of CoreValve and SAPIEN XT appears to
      be reached with different degrees of oversizing. Certain annular sizes that allow
      for only moderate or large oversizing, but not both, appear to benefit from a
      device specific approach.

PMID- 25573785
TI  - Finasteride use and acute pancreatitis in Taiwan.
AB  - The aim of this study was to examine whether there is an association between
      finasteride use and the risk of acute pancreatitis. This population-based case
      control study used the database of the Taiwan National Health Insurance Program.
      There were 2,530 male subjects aged 40-84 years with a first-attack of acute
      pancreatitis during the period of 1998-2011 as the case group and 10,119 randomly
      selected subjects without acute pancreatitis as the control group. Both groups
      were matched by age and index year of diagnosing acute pancreatitis. Subjects who
      never had finasteride prescription were defined as "never use." Subjects who at
      least received 1 prescription for finasteride before the date of diagnosing acute
      pancreatitis were defined as "ever use." The association of acute pancreatitis
      with finasteride use was examined by the odds ratio (OR) and 95% confidence
      interval (CI) using the multivariable unconditional logistic regression model.
      The crude OR of acute pancreatitis was 1.78 (95%CI 1.33, 2.39) for subjects with
      ever use of finasteride, when compared with subjects with never use of
      finasteride. After adjusting for potential confounders, the adjusted OR of acute
      pancreatitis decreased to 1.25 (95%CI 0.90, 1.73) for subjects with ever use of
      finasteride, but no statistical significance was seen. No association can be
      detected between finasteride use and the risk of acute pancreatitis. 

PMID- 25573786
TI  - Reproductive toxicity of 1-nitronaphthalene and 1-nitropyrene exposure in the
      mummichog, Fundulus heteroclitus.
AB  - After pregnant mummichog were implanted with 1-nitronaphthalene or 1-nitropyrene
      via cholesterol pellet, we investigated the effects of the chemicals on embryo
      normality, hatchability and days to hatch of normal embryos, and growth and
      survival of hatched larvae from normal embryos of the implanted mummichog.
      Hatchability was the parameter most sensitive to the effects of both 1
      nitronaphthalene and 1-nitropyrene. The 4-week lowest-observed-effect
      concentration (LOEC) of 1-nitronaphthalene, based on the actual concentrations in
      the eggs in the test, was 447 ng g(-1) wet wt.; and the LOEC and no-observed
      effect concentration (NOEC) of 1-nitropyrene were 958 and 344 ng g(-1) wet wt.,
      respectively. The 4-week LOEC of 1-nitronaphthalene, based on the concentration
      in the water, was estimated at 4.8 ug L(-1) by using the reported
      bioconcentration factor; and the LOEC and NOEC of 1-nitropyrene, based on the
      concentration in the water, were estimated at 3.1 and 8.6 ug L(-1), respectively.
      The reported environmental concentrations of 1-nitropyrene and 1-nitronaphthalene
      are over three magnitudes lower than the toxicity values we obtained. Therefore,
      the effects of environmental levels of 1-nitropyrene and 1-nitronaphthalene on
      fish reproduction, not including genomic effects on embryos, appear to be almost
      negligible. However, DNA damage has been detected in marine organisms exposed to
      1-nitropyrene. Further studies of the genotoxicity of nitrated polycyclic
      aromatic hydrocarbons at environmental levels are therefore needed to evaluate
      their ecotoxicological risks. 

PMID- 25573787
TI  - Calcium hydroxide medication in primary molars using different preparations and
      placement techniques: an in vitro study.
AB  - AIM: This was to compare the effectiveness of different preparations and delivery
      techniques of calcium hydroxide paste as an intracanal medicament in primary
      molar root canals. METHODS: Extracted lower primary second molars roots (72) were
      randomly assigned to the four experimental groups. After complete root canal
      preparation with TF rotary nickel titanium up to .06/30 file, a mix of calcium
      hydroxide/ distilled water was delivered by lentulo spiral (group 1) or a syringe
      (group 2). UltraCal((r)) XS was placed by lentulo spiral (group 3) and a syringe
      (group 4). Digital radiographs were taken in both buccal and proximal directions
      before and after calcium hydroxide placement to evaluate the quality of filling.
      The mean percentages of filled calcium hydroxide area by subtracted digital
      radiograph, and the quality assessments between four experimental groups, were
      compared by using Two-way ANOVA and Fisher's exact test respectively. A p value
      of less than 0.05 was considered statistical significance. RESULTS: There was no
      statistically significant difference in the mean percentages of the filled
      calcium hydroxide area among different preparations and delivery techniques (p >=
      0.05). The syringe technique had statistically significant fewer of air
      inclusions than when using the lentulo spiral with the mix of calcium hydroxide
      group (p < 0.05). The completeness of obturation and the quality of filling at
      apical part were not different among groups (p >= 0.05). CONCLUSION: Syringe
      technique was a simpler handling method that presented similar filling quality
      but fewer porosities than lentulo spiral technique in primary molar root canals.

PMID- 25573788
TI  - Blinded double reading yields a higher programme sensitivity than non-blinded
      double reading at digital screening mammography: a prospected population based
      study in the south of The Netherlands.
AB  - PURPOSE: To prospectively determine the screening mammography outcome at blinded
      and non-blinded double reading in a biennial population based screening programme
      in the south of the Netherlands. METHODS: We included a consecutive series of
      87,487 digital screening mammograms, obtained between July 2009 and July 2011.
      Screening mammograms were double read in either a blinded (2nd reader was not
      informed about the 1st reader's decision) or non-blinded fashion (2nd reader was
      informed about the 1st reader's decision). This reading strategy was alternated
      on a monthly basis. Women with discrepant readings between the two radiologists
      were always referred for further analysis. During 2 years follow-up, we collected
      the radiology reports, surgical correspondence and pathology reports of all
      referred women and interval breast cancers. RESULTS: Respectively 44,491 and
      42,996 screens had been read either in a blinded or non-blinded fashion. Referral
      rate (3.3% versus 2.8%, p<0.001) and false positive rate (2.6% versus 2.2%,
      p=0.002) were significantly higher at blinded double reading whereas the cancer
      detection rate per 1000 screens (7.4 versus 6.5, p=0.14) and positive predictive
      value of referral (22% versus 23%, p=0.51) were comparable. Blinded double
      reading resulted in a significantly higher programme sensitivity (83% versus 76%,
      p=0.01). Per 1000 screened women, blinded double reading would yield 0.9 more
      screen detected cancers and 0.6 less interval cancers than non-blinded double
      reading, at the expense of 4.4 more recalls. CONCLUSION: We advocate the use of
      blinded double reading in order to achieve a better programme sensitivity, at the
      expense of an increased referral rate and false positive referral rate.

PMID- 25573789
TI  - Molecular modeling of the human sperm associated antigen 11 B (SPAG11B) proteins.
AB  - Antimicrobial proteins and peptides are ubiquitous in nature with diverse
      structural and biological properties. Among them, the human beta-defensins are
      known to contribute to the innate immune response. Besides the defensins, a
      number of defensin-like proteins and peptides are expressed in many organ systems
      including the male reproductive system. Some of the protein isoforms encoded by
      the sperm associated antigen 11B (SPAG11) gene in humans are beta-defensin-like
      and exhibit structure dependent and salt tolerant antimicrobial activity, besides
      contributing to sperm maturation. Though some of the functional roles of these
      proteins are reported, the structural and molecular features that contribute to
      their antimicrobial activity is not yet reported. In this study, using in silico
      tools, we report the three dimensional structure of the human SPAG11B proteins
      and their C-terminal peptides. web-based hydropathy, amphipathicity, and topology
      (WHAT) analyses and grand average of hydropathy (GRAVY) indices show that these
      proteins and peptides are amphipathic and highly hydrophilic. Self-optimized
      prediction method with alignment (SOPMA) analyses and circular dichroism data
      suggest that the secondary structure of these proteins and peptides primarily
      contain beta-sheet and random coil structure and alpha-helix to a lesser extent.
      Ramachandran plots show that majority of the amino acids in these proteins and
      peptides fall in the permissible regions, thus indicating stable structures. The
      secondary structure of SPAG11B isoforms and their peptides were not perturbed
      with increasing NaCl concentration (0-300 mM) and at different pH (3, 7, and 10),
      thus reinforcing our previously reported observation that their antimicrobial
      activity is salt tolerant. To the best of our knowledge, for the first time,
      results of our study provide vital information on the structural features of
      SPAG11B protein isoforms and their contribution to antimicrobial activity. 

PMID- 25573790
TI  - Application of multiple levels of fluid shear stress to endothelial cells plated
      on polyacrylamide gels.
AB  - Measurements of endothelial cell response to fluid shear stress have previously
      been performed on unphysiologically rigid substrates. We describe the design and
      implementation of a microfluidic device that applies discrete levels of shear
      stress to cells plated on hydrogel-based substrates of physiologically-relevant
      stiffness. The setup allows for measurements of cell morphology and inflammatory
      response to the combined stimuli, and identifies mechanisms by which vascular
      stiffening leads to pathological responses to blood flow. We found that the
      magnitude of shear stress required to affect endothelial cell morphology and
      inflammatory response depended on substrate stiffness. Endothelial cells on 100
      Pa substrates demonstrate a greater increase in cell area and cortical stiffness
      and decrease in NF-kappaB nuclear translocation in response to TNF-alpha
      treatment compared to controls than cells plated on 10 kPa substrates. The
      response of endothelial cells on soft substrates to shear stress depends on the
      presence of hyaluronan (HA). These results emphasize the importance of substrate
      stiffness on endothelial function, and elucidate a means by which vascular
      stiffening in aging and disease can impact the endothelium. 

PMID- 25573792
TI  - Conidial vigor vs. viability as predictors of virulence of entomopathogenic
      fungi.
AB  - We tested the hypothesis that debilitated conidia exhibiting slow-germination
      (requiring>16h to germinate) are less virulent than vigorous conidia exhibiting
      fast germination (requiring?16h to germinate). Preparations of Beauveria bassiana
      s.l. strain CG 1027 with variable ratios of vigorous to debilitated conidia were
      assayed against third-instar larvae of Spodoptera frugiperda. As the proportion
      of debilitated conidia in test preparations increased, LC50 expressed in terms of
      total viable conidia increased, while LC50 expressed solely in terms of vigorous
      conidia remained constant, indicating that vigorous conidia were responsible for
      nearly all mortality observed in the assays. Larvae treated with conidia from low
      quality batches (with high proportions of debilitated conidia) survived
      consistently longer than those treated with comparable doses of conidia from high
      quality batches. These results confirm our previous hypotheses that inclusion of
      debilitated conidia in viability assessments can lead to overestimation of the
      quality (potency) of mycoinsecticide preparations and support our recommendation
      for use of short incubation periods for assessing viability whenever viability is
      relied upon as an indicator of product quality. 

PMID- 25573791
TI  - Human immunodeficiency virus (HIV)-1 integration sites in viral latency.
AB  - The persistence of human immunodeficiency virus type 1 (HIV-1) in latent
      reservoirs is a major barrier to HIV cure. Reservoir establishment depends on low
      viral expression that may be related to provirus integration sites (IS). In
      vitro, in cell lines and primary T cells, latency is associated with specific IS
      through reduced viral expression mediated by transcriptional interference by host
      cellular promoters, reverse orientation, and the presence of specific epigenetic
      modifiers. In primary T cell models of latency, specific IS are associated with
      intracellular viral antigen expression that is not directly related to cell
      activation. In contrast, in patient CD4+ T cells, there is enrichment for IS in
      genes controlling cell cycle and survival and in some clonally expanded T cell
      subpopulations. Multiple insertion sites within some specific genes may suggest
      that integrated HIV can increase the host's T cell survival. 

PMID- 25573794
TI  - Correction to "master regulators, regulatory networks, and pathways of
      glioblastoma subtypes".
AB  - [This corrects the article on p. 33 in vol. 13, PMID: 25368508.]. 

PMID- 25573793
TI  - Silencing SlELP2L, a tomato Elongator complex protein 2-like gene, inhibits leaf
      growth, accelerates leaf, sepal senescence, and produces dark-green fruit.
AB  - The multi-subunit complex Elongator interacts with elongating RNA polymerase II
      (RNAPII) and is thought to facilitate transcription through histone acetylation.
      Elongator is highly conserved in eukaryotes, yet has multiple kingdom-specific
      functions in diverse organisms. Recent genetic studies performed in Arabidopsis
      have demonstrated that Elongator functions in plant growth and development, and
      in response to biotic and abiotic stress. However, little is known about its
      roles in other plant species. Here, we study the function of an Elongator complex
      protein 2-like gene in tomato, here designated as SlELP2L, through RNAi-mediated
      gene silencing. Silencing SlELP2L in tomato inhibits leaf growth, accelerates
      leaf and sepal senescence, and produces dark-green fruit with reduced GA and IAA
      contents in leaves, and increased chlorophyll accumulation in pericarps. Gene
      expression analysis indicated that SlELP2L-silenced plants had reduced transcript
      levels of ethylene- and ripening-related genes during fruit ripening with
      slightly decreased carotenoid content in fruits, while the expression of DNA
      methyltransferase genes was up-regulated, indicating that SlELP2L may modulate
      DNA methylation in tomato. Besides, silencing SlELP2L increases ABA sensitivity
      in inhibiting seedling growth. These results suggest that SlELP2L plays important
      roles in regulating plant growth and development, as well as in response to ABA
      in tomato. 

PMID- 25573795
TI  - Maternal Serum S100-B, PAPP-A and IL-6 levels in severe preeclampsia.
AB  - AIM: We aimed to investigate the relationship of maternal serum levels of S100-B,
      PAPP-A and IL-6 with severe preeclampsia. MATERIALS AND METHODS: This prospective
      case-control study consisted of 27 severe preeclamptic and 36 healthy singleton
      pregnancies. The groups were matched for parity, maternal age and body mass
      index. Maternal blood sampling for S100B, PAPP-A and IL-6 was performed at the
      morning after an overnight fasting. RESULTS: S100-B concentrations were
      significantly higher in severe preeclampsia group (0.09 +/- 0.05 vs. 0.13 +/-
      0.01 ug/L; p = 0.025). PAPP-A levels were higher (196.54 +/- 21.56 vs. 208.80 +/-
      23.97 mIU/ml; p = 0.707) and IL-6 levels were lower in severe preeclamptic group
      (68.79 +/- 29.89 vs. 37.30 +/- 6.46 pg/ml; p = 0.372). AUC value for S100-B was
      calculated as 0.712. When cutoff level for serum S100-B for predicting severe
      preeclampsia was regarded as 0.0975 ug/L, sensitivity and specificity were found
      to be 81.4 % and 58.3 %, respectively. Pregnancies with >=0.0975 ug/L S100-B
      levels had 12.75-fold increased risk for having CNS symptoms (OR 12.75; 95 % CI
      2.69-60.28) and 3.27-fold increased risk for having HELLP syndrome (OR 3.27; 95 %
      CI 0.62-17.36). CONCLUSION: Our results suggest that serum S100B levels may be a
      potential marker in severe preeclampsia for the severity of hypoperfusion both in
      placenta and brain pointing at subsequent risk of organ failure.

PMID- 25573796
TI  - Intrapartum care and substandard care: juridical recommendations to reduce the
      risk of liability.
AB  - PURPOSE: To develop juridical recommendations to reduce medical liability of the
      obstetrician, providing intrapartum care. METHODS: 107 legal proceedings of the
      past 40 years from Belgium, France and the Netherlands, involving medical
      negligence of the obstetrician during intrapartum care, were analyzed in depth.
      The legal databases used were Jura and Judit (Belgium), Legifrance, Juricaf and
      Dalloz (France) and Recht, Rechtspraak (the Netherlands). A minority of the cases
      were retrieved through contacts with insurance companies (Belgium only) and
      courts. RESULTS: The judicial assessment of negligence is focused on four domains
      of expertise of the obstetrician: 36 % (38/107) recognizing a specific pathology,
      33 % (35/107) interpreting fetal monitoring, 19 % (21/107) performing a
      forceps/vacuum-assisted delivery and 12 % (13/107) managing shoulder dystocia.
      The highest liability rate of 86 % (30/35) was reflected in the category of
      interpreting fetal monitoring. CONCLUSION: To reduce the liability rate of 66 %,
      several policy recommendations can be made. Respond to the first symptoms of
      obstetric complications (particularly placental abruption and uterine rupture).
      Secondly, respond to disturbing messages of the midwife concerning fetal distress
      and evaluate every deviation in fetal heart rate monitoring. Education concerning
      the interpretation of fetal monitoring is a must for every midwife and
      obstetrician. Use proper methods to monitor the heart rate to optimize the
      quality of the signal. The third recommendation is to be cautious about opting
      for a forceps/vacuum-assisted delivery, consider all circumstances. Consider the
      risk of failed instrumental delivery. And finally in relation to shoulder
      dystocia, recognize the risk factors by ordering further examinations to purchase
      a diagnosis.

PMID- 25573798
TI  - Novel scalable 3D cell based model for in vitro neurotoxicity testing: Combining
      human differentiated neurospheres with gene expression and functional endpoints.
AB  - There is an urgent need for new in vitro strategies to identify neurotoxic agents
      with speed, reliability and respect for animal welfare. Cell models should
      include distinct brain cell types and represent brain microenvironment to attain
      higher relevance. The main goal of this study was to develop and validate a human
      3D neural model containing both neurons and glial cells, applicable for toxicity
      testing in high-throughput platforms. To achieve this, a scalable bioprocess for
      neural differentiation of human NTera2/cl.D1 cells in stirred culture systems was
      developed. Endpoints based on neuronal- and astrocytic-specific gene expression
      and functionality in 3D were implemented in multi-well format and used for
      toxicity assessment. The prototypical neurotoxicant acrylamide affected primarily
      neurons, impairing synaptic function; our results suggest that gene expression of
      the presynaptic marker synaptophysin can be used as sensitive endpoint.
      Chloramphenicol, described as neurotoxicant affected both cell types, with
      cytoskeleton markers' expression significantly reduced, particularly in
      astrocytes. In conclusion, a scalable and reproducible process for production of
      differentiated neurospheres enriched in mature neurons and functional astrocytes
      was obtained. This 3D approach allowed efficient production of large numbers of
      human differentiated neurospheres, which in combination with gene expression and
      functional endpoints are a powerful cell model to evaluate human neuronal and
      astrocytic toxicity. 

PMID- 25573797
TI  - Soft tissue ossification and condylar cartilage degeneration following TMJ disc
      perforation in a rabbit pilot study.
AB  - OBJECTIVE: There are limited clinical treatments for temporomandibular joint
      (TMJ) pathologies, including degenerative disease, disc perforation and
      heterotopic ossification (HO). One barrier hindering the development of new
      therapies is that animal models recapitulating TMJ diseases are poorly
      established. The objective of this study was to develop an animal model for TMJ
      cartilage degeneration and disc pathology, including disc perforation and soft
      tissue HO. METHODS: New Zealand white rabbits (n = 9 rabbits) underwent
      unilateral TMJ disc perforation surgery and sham surgery on the contralateral
      side. A 2.5 mm defect was created using a punch biopsy in rabbit TMJ disc. The
      TMJ condyles and discs were evaluated macroscopically and histologically after 4,
      8 and 12 weeks. Condyles were blindly scored by four independent observers using
      OARSI recommendations for macroscopic and histopathological scoring of
      osteoarthritis (OA) in rabbit tissues. RESULTS: Histological evidence of TMJ
      condylar cartilage degeneration was apparent in experimental condyles following
      disc perforation relative to sham controls after 4 and 8 weeks, including surface
      fissures and loss of Safranin O staining. At 12 weeks, OARSI scores indicated
      experimental condylar cartilage erosion into the subchondral bone. Most
      strikingly, HO occurred within the TMJ disc upon perforation injury in six
      rabbits after 8 and 12 weeks. CONCLUSION: We report for the first time a rabbit
      TMJ injury model that demonstrates condylar cartilage degeneration and disc
      ossification, which is indispensible for testing the efficacy of potential TMJ
      therapies.

PMID- 25573799
TI  - [Brain radiation necrosis after stereotactic radiotherapy of the resection cavity
      for intracranial metastases: analysis of the literature from four cases].
AB  - Stereotactic hypofractionated radiotherapy after resection of brain metastasis is
      an alternative to whole brain radiotherapy. A high dose per fraction is
      associated with a risk of radiation necrosis. We present four cases of confirmed
      histological radiation necrosis. Differentiating recurrent tumour from radiation
      necrosis in this scenario is challenging. An enhancing area in magnetic resonance
      imaging (MRI) with a "cut bell pepper" appearance may suggest radiation necrosis.
      Advanced imaging modalities such as perfusion MR imaging and positron emission
      tomography can be useful. Dosimetric predictors of the occurrence of radiation
      necrosis after stereotactic hypofractionated radiotherapy are poorly understood
      and require prospective studies on larger cohorts. 

PMID- 25573800
TI  - Integrating spatial land use analysis and mathematical material flow analysis for
      nutrient management: a case study of the Bang Pakong River Basin in Thailand.
AB  - Rivers in developing and emerging countries often lack good water quality. Tools
      to assess the water quality in rivers, including identification of possible
      sources of pollution, are therefore of increasing importance. The aim of this
      study is to apply mathematical material flow and spatial land use analyses to
      identify and geographically locate the main nitrogen and phosphorus sources and
      processes in Bang Pakong Basin (BPB). Potential measures to mitigate the nitrogen
      and phosphorus loads to the water system can then be efficiently evaluated. The
      combination of these two methods reveals the overall nutrient load as well as
      local "hot spots." This allows possible mitigation measures to be discussed with
      regard to their spatial location. This approach goes beyond previous work in
      which mathematical material flow analysis was shown to be a useful tool to
      investigate sources of nutrients regardless of their location. The results show
      that the main sources contributing nutrients to waterways are aquaculture, such
      as shrimp, tilapia, catfish, and sea bass farming, as well as rice paddies along
      the main river. Additional sources contributing nutrients to this basin are field
      crops, livestock, aquaculture, households, and industry. High levels of nutrient
      inflows come from feeds and fertilizers through aquaculture and rice cultivation.
      The excess nutrients run into the waterways by direct discharge from aquaculture
      and runoff processes from rice paddies. Scenario analysis shows that management
      practices for aquaculture, rice, pig, and poultry farming are key drivers for
      reducing nutrients in the BPB. 

PMID- 25573801
TI  - An adaptive watershed management assessment based on watershed investigation
      data.
AB  - The aim of this study was to assess the states of watersheds in South Korea and
      to formulate new measures to improve identified inadequacies. The study focused
      on the watersheds of the Han River basin and adopted an adaptive watershed
      management framework. Using data collected during watershed investigation
      projects, we analyzed the management context of the study basin and identified
      weaknesses in water use management, flood management, and environmental and
      ecosystems management in the watersheds. In addition, we conducted an interview
      survey to obtain experts' opinions on the possible management of watersheds in
      the future. The results of the assessment show that effective management of the
      Han River basin requires adaptive watershed management, which includes
      stakeholders' participation and social learning. Urbanization was the key
      variable in watershed management of the study basin. The results provide strong
      guidance for future watershed management and suggest that nonstructural measures
      are preferred to improve the states of the watersheds and that consistent
      implementation of the measures can lead to successful watershed management. The
      results also reveal that governance is essential for adaptive watershed
      management in the study basin. A special ordinance is necessary to establish
      governance and aid social learning. Based on the findings, a management process
      is proposed to support new watershed management practices. The results will be of
      use to policy makers and practitioners who can implement the measures recommended
      here in the early stages of adaptive watershed management in the Han River basin.
      The measures can also be applied to other river basins. 

PMID- 25573803
TI  - Dual function of IL-33 on proliferation of NIH-3T3 cells.
AB  - The interleukin-33 (IL-33)-ST2L signaling pathway has been shown to play
      important roles in the field of immunology, especially as a trigger for allergic
      reactions such as bronchial asthma. However, coming back to the original finding
      that the ST2 gene is induced during initiation of the cell cycle of fibroblastic
      cell lines, the possible functions of the ST2 gene products and their specific
      ligand, IL-33, in the field of cell growth regulation are still interesting
      problems to be solved. In this study, we used NIH-3T3 mouse cell line and added
      IL-33 before and after cell proliferation assay, which revealed the dual function
      of IL-33. When IL-33 was added to the confluent cells before the start of cell
      proliferation, it suppressed the cell growth concentration-dependently. On the
      other hand, if IL-33 was added after the start of cell proliferation, it enhanced
      the cell growth. The negative effect of IL-33 on cell proliferation is a novel
      finding and would provide an important clue to the roles of IL-33 and ST2/ST2L in
      growth regulation. 

PMID- 25573804
TI  - Heparan sulfate proteoglycans fine-tune macrophage inflammation via IFN-beta.
AB  - Macrophages are important mediators of diseases associated with metabolic
      inflammation such as obesity and atherosclerosis. In this Stimulus we discuss
      recent findings showing that heparan sulfate proteoglycans on macrophages serve
      as an important inflammatory rheostat. This observation has significant
      implications as the degree of macrophage proteoglycan sulfation can determine and
      possibly predict disease outcomes of metabolic inflammatory disorders. 

PMID- 25573802
TI  - Chemobrain: a critical review and causal hypothesis of link between cytokines and
      epigenetic reprogramming associated with chemotherapy.
AB  - One consequence of modern cancer therapy is chemotherapy related cognitive
      dysfunction or "chemobrain", the subjective experience of cognitive deficits at
      any point during or following chemotherapy. Chemobrain, a well-established
      clinical syndrome, has become an increasing concern because the number of long
      term cancer survivors is growing dramatically. There is strong evidence that
      correlates changes in peripheral cytokines with the development of chemobrain in
      commonly used chemotherapeutic drugs for different types of cancer. However, the
      mechanisms by which these cytokines elicit change in the central nervous system
      are still unclear. In this review, we hypothesize that the administration of
      chemotherapy agents initiates a cascade of biological changes, with short-lived
      alterations in the cytokine milieu inducing persistent epigenetic alterations.
      These epigenetic changes lead to changes in gene expression, alterations in
      metabolic activity and neuronal transmission that are responsible for generating
      the subjective experience of cognition. This speculative but testable hypothesis
      should help to gain a comprehensive understanding of the mechanism underlying
      cognitive dysfunction in cancer patients. Such knowledge is critical to identify
      pharmaceutical targets with the potential to prevent and treat cancer-treatment
      related cognitive dysfunction and similar disorders. 

PMID- 25573806
TI  - Enhancing the copper(II) complexes cytotoxicity to cancer cells through bound to
      human serum albumin.
AB  - We use Schiff-base salicylaldehyde benzoylhydrazone (HL) as the ligand for
      copper(II), resulting in the complexes [CuCl(L)].H2O (C1), [CuNO3(L)].H2O (C2)
      and [CuBr(L)]2 (C3). We characterize the Cu(II) compounds' interactions with
      human serum albumin (HSA) using fluorescence spectroscopy and molecular docking.
      These studies revealed that Cu(II) compounds propensity bound to IIA subdomain of
      HSA possible by hydrophobic interactions and hydrogen bond. Cu(II) compounds
      produce intracellular reactive oxygen species (ROS) in cancer cells. Complexes of
      HSA and copper(II) compounds enhance about 2-fold cytotoxicity in cancer cells
      but do not raise cytotoxicity levels in normal cells in vitro. Compared with C3
      alone, HSA-C3 complex promotes HepG2 cell apoptosis and has a stronger capacity
      to promote cell cycle arrest at the G2/M phase of HepG2. 

PMID- 25573805
TI  - Protective effects of Sparstolonin B, a selective TLR2 and TLR4 antagonist, on
      mouse endotoxin shock.
AB  - Sepsis is characterized by an overwhelming systemic inflammation and multiple
      organ injury. Toll-like receptors (TLRs) 2 and 4 mediate these inflammatory
      responses. Sparstolonin B (SsnB), isolated from Chinese herb Scirpus yagara, is a
      new selective TLR2/4 antagonist. Herein, we report that SsnB inhibited the
      expression of various inflammatory mediators such as tumor necrosis factor (TNF
      alpha), interleukin (IL)-1beta, IL-6, and chemokine (C-C motif) ligand 2 (CCL-2)
      in lipopolysaccharide (LPS)- or Pam3csk4-stimulated macrophages. Moreover, in LPS
      stimulated macrophages, the downregulation of peroxisome proliferator-activated
      receptor gamma (PPAR-gamma) was reversed by SsnB dose-dependently; and SsnB had
      synergistic inhibitory effects with rosiglitazone, a PPAR-gamma agonist, on TNF
      alpha and IL-6 expression in LPS-stimulated macrophages. The effects of SsnB were
      further evaluated in a mouse endotoxin shock model. When intraperitoneal injected
      in mice 2 days before or 1-2h after LPS challenge, SsnB attenuated the body
      temperature reduction and decreased the mortality. SsnB pre-treatment
      significantly suppressed LPS-induced increase of TNF-alpha and IL-6 in serum,
      lungs and livers, and substantially attenuated lung dysfunction in mice. In vivo
      toxicity test showed that at doses as high as 500 mg/kg, SsnB did not cause death
      of mice. These results suggest that SsnB protects mice against endotoxin shock by
      inhibiting production of multiple cytokines and lung dysfunction. In conclusion,
      our findings indicate that SsnB may be used in the prevention and treatment of
      endotoxin shock.

PMID- 25573807
TI  - Body mass index, body fat, and nutritional status of patients with heart failure:
      The PLICA study.
AB  - BACKGROUND & AIMS: Nutritional assessment may help to explain the incompletely
      understood obesity paradox in patients with heart failure (HF). Currently,
      obesity is usually identified by body mass index (BMI). Our objective was to
      assess the prognostic influence of undernourishment in HF outpatients. METHODS:
      Two published definitions of undernourishment were used to assess 214 ambulatory
      HF patients. Definition 1 included albumin, total lymphocyte count, tricipital
      skinfold (TS), subscapular skinfold, and arm muscle circumference (AMC)
      measurements (>=2 below normal considered undernourishment). Definition 2
      included TS, AMC, and albumin (>=1 below normal considered undernourishment).
      Patients were also stratified by BMI and body fat percentage and followed for 2
      years. All-cause death or HF hospitalization was the primary endpoint. RESULTS:
      Based on BMI strata, among underweight patients, 60% and 100% were undernourished
      by Definitions 1 and 2, respectively (31% and 44% among normal-weight, 4% and 11%
      among overweight, and 0% and 3% among obese patients, respectively, according to
      the two definitions). The most prevalent undernourishment type was marasmus-like
      (18% of the total cohort). Undernourishment by both definitions was significantly
      associated with lower event-free survival. Following multivariable analysis, age,
      NYHA functional class, NTproBNP, and undernourishment (hazard ratio [HR] 2.25
      [1.11-4.56] and 2.24 [1.19-4.21] for Definitions 1 and 2, respectively) remained
      in the model. In this cohort, BMI and percentage of body fat did not
      independently predict 2-year event-free survival. CONCLUSIONS: Nutritional status
      is a key prognostic factor in HF above and beyond BMI and percentage of body fat.
      Patients in normal BMI range and even in overweight and obese groups showed
      undernourishment. The high mortality observed in undernourishment, infrequent in
      high BMI patients, may help to partly explain the obesity paradox. Proper
      undernourishment assessment should become routine in patients with HF.

PMID- 25573809
TI  - A rare case of clear cell carcinoma of the breast evaluated by (18)F-FDG PET/CT.

PMID- 25573808
TI  - Scintigraphic depiction of non-ossifying fibromas and the role of SPECT/CT.
AB  - Non-ossifying fibromas (NOF) are a benign entity of the developing bone,
      relatively common in children and young adults. Their location is most frequently
      metaphyseal. They are usually asymptomatic (unless associated to a fracture) and
      have a self-limited behavior, with spontaneous regression through a sclerotic
      consolidation. Plain X-ray is the main imaging tool for its diagnosis. However,
      an unclear X-ray may lead to further imaging studies. We present the case of a 17
      year-old male with back pain and lower limb dysmetria referred for a bone
      scintigraphy to complete the diagnostic and assess disease extension and the
      subsequent MRI evaluation. 

PMID- 25573811
TI  - Pre and post-operative psychological functioning in younger and older children
      with microtia.
AB  - OBJECTIVES: Microtia ranges from a smaller ear to the absence of the external ear
      and has been associated with psychosocial distress. Traditional ear
      reconstruction takes place beginning at age six. Use of an alloplastic implant
      allows for earlier surgery starting at age three, which may reduce potential
      negative psychological effects. However, few studies have examined psychosocial
      outcomes of ear reconstruction with groups that include young children. METHODS:
      Children (N = 23) with microtia and their parents completed two microtia-related
      scales, negative emotions and microtia social awareness, and the Behavioral
      Assessment System for Children - Second Edition (BASC-2) subscales of anxiety,
      depression, and social skills before surgery and one year after surgery.
      Participants (74% male) were three to nine years old with a mean age of 6.13 +/-
      2.10 years and were grouped by age at surgery, three to six years (n = 11) or
      seven to ten years (n = 12). The sample identified as Latino (96%) or "other"
      (4%). RESULTS: Pre and postoperative scores by age group were compared using two
      way repeated measures analyses of variance. Children and parents reported
      significantly less negative emotion and microtia social awareness following
      surgery, with an interaction for parental report of older children showing higher
      negative emotion preoperatively. Older children also had higher scores of
      depression and anxiety before surgery and both groups reported significant
      decreases following surgery, along with improved social skills. Older children
      showed significantly greater gains in social skills. CONCLUSION: All participants
      and their parents reported improved psychological functioning postoperatively.
      However, older children may be at greater risk of psychological concerns given
      the longer time they have to cope with the impact of microtia on self-image and
      exposure to social stressors. Undergoing reconstructive surgery earlier may be a
      protective factor for children with microtia.

PMID- 25573810
TI  - Incidentally detected right-to-left intracardiac shunt with Eisenmenger syndrome
      on V/Q SPECT/CT.

PMID- 25573812
TI  - Analysis of the mitochondrial proteome in cytoplasmic male-sterile and male
      fertile beets.
AB  - The reported analyses were aimed at identification of the mitochondrial proteome
      features which were associated with cytoplasmic male sterility (CMS) in beets.
      The set of analyzed accessions included CMS, maintainer and restored lines.
      Mitochondrial preparations were subjected to blue-native electrophoresis followed
      either by in-gel activity assays or separation in denaturing conditions. The CMS
      condition was associated with decreased activity of complex V and enhancement of
      additional complexes with the ATPase activity. This was accompanied by
      accumulation of heptamer HSP60, preSATP6 and an increase in the fraction of the
      free ATP9 oligomer (not bound to complex V). The ATP9 effect was reversed upon
      fertility restoration. BIOLOGICAL SIGNIFICANCE: The reported work provides one of
      very few comprehensive comparisons of the mitochondrial proteomes from
      cytoplasmic male-sterile (CMS) and male-fertile plants. It shows that in beets
      the CMS trait is associated with altered functioning of the mitochondrial ATP
      synthase complex. The presence of CMS-specific ATP synthase subcomplexes
      resembles deficiencies of this enzyme reported for mammalian cells.

PMID- 25573813
TI  - Usefulness of the oblique coronal plane in ankle MRI of the calcaneofibular
      ligament.
AB  - AIM: To evaluate the usefulness and diagnostic accuracy of oblique coronal MRI of
      the calcaneofibular ligament (CFL) view for diagnosis of CFL injury. MATERIAL AND
      METHODS: This retrospective study included 91 patients who were suspected to have
      CFL injury who underwent CFL view imaging. Anatomical identification of the CFL
      on orthogonal MRI sequences and CFL views was evaluated. Two radiologists
      evaluated the CFL based on an entire length view, an entire width view, and
      margin sharpness using a four-point scale. Diagnostic accuracy using orthogonal
      and CFL views was evaluated by calculating sensitivity, specificity, and
      accuracy. Arthroscopic or clinical findings were used as the reference standard.
      RESULTS: Both readers found identification of lesions using the entire length,
      entire width, and sharp margin from CFL view images to be superior to that based
      on orthogonal images. The sensitivity and accuracy of diagnosing CFL injury were
      significantly higher when using the CFL view compared to the orthogonal view,
      although specificity was not significantly different between the CFL view and
      orthogonal view images. CONCLUSIONS: CFL view imaging enables better anatomical
      evaluation and improved sensitivity and accuracy of diagnosis of CFL injury. CFL
      view images should therefore be used to evaluate potential CFL injuries.

PMID- 25573814
TI  - Opacification of the middle ear and mastoid: imaging findings and clues to
      differential diagnosis.
AB  - Opacification of the middle ear and mastoid represents a spectrum of
      inflammatory, neoplastic, vascular, fibro-osseous, and traumatic changes. This
      article reviews the most important clinical and pathological characteristics,
      emphasizing CT and MRI findings. Knowledge of subtle patterns of middle ear and
      mastoid opacification at CT and MRI provide guidance towards the correct
      diagnosis.

PMID- 25573815
TI  - Synthesis of enantioenriched 5,6-dihydrophenanthridine derivatives through retro
      carbopalladation of chiral o-bromobenzylamines.
AB  - Retro-carbopalladation of aldimines in the presence of a suitable beta-hydrogen
      atom has been observed in the Pd-catalyzed homocoupling reactions of o
      bromobenzylamines, providing an expeditious synthetic route to 5,6
      dihydrophenanthridine derivatives. Furthermore, a highly enantioselective
      synthesis of 6-aryl-substituted 5,6-dihydrophenanthridines was achieved in a one
      pot manner by taking advantage of Rh and Pd catalysis. 

PMID- 25573817
TI  - Highly efficient dehydrogenative coupling of hydrosilanes with amines or amides
      using supported gold nanoparticles.
AB  - Hydroxyapatite-supported gold nanoparticles (Au/HAP) can act as a highly active
      and reusable catalyst for the coupling of hydrosilanes with amines under mild
      conditions. Various silylamines can be selectively obtained from diverse
      combinations of equimolar amounts of hydrosilanes with amines including less
      reactive bulky hydrosilanes. This study also highlights the applicability of
      Au/HAP to the selective synthesis of silylamides through the coupling of
      hydrosilanes with amides, demonstrating the first example of an efficient
      heterogeneous catalyst. Moreover, Au/HAP shows high reusability and applicability
      for gram-scale synthesis. 

PMID- 25573816
TI  - Association between body size phenotype and sleep duration: Korean National
      Health and Nutrition Examination Survey V (KNHANES V).
AB  - OBJECTIVE: Recent studies reported the presence of unique subsets of body size
      phenotypes that are more susceptible or more resistant to the development of
      obesity-associated metabolic disorders, although the underlying mechanism is not
      yet fully elucidated. We investigated the association between body size
      phenotypes and sleep duration after adjusting potential confounding factors.
      MATERIALS AND METHODS: We analyzed data from the Korean National Health and
      Nutrition Examination Survey V (KNHANES V), a nation-wide, population-based
      health survey including 9077 Korean adults. The average amount of sleep per night
      was categorized as: <=6, 7, 8, and >=9 h. Body size phenotypes were classified
      based on body mass index (BMI) and presence of metabolic syndrome; metabolically
      healthy and normal weight (MHNW), metabolically abnormal but normal weight
      (MANW), metabolically healthy but obese (MHO), and metabolically abnormal obese
      (MAO). RESULTS: According to sleep duration, there were significant differences
      in age, gender, BMI, waist circumference, and blood pressure (all P <0.05).
      Multivariate analysis showed that obese groups (MHO and MAO) had significantly
      shorter sleep durations than non-obese groups (MHNW and MANW) (6.78+/-0.04 vs.
      6.93+/-0.03, P <0.001). Sleep duration was significantly different according to
      body size phenotype, irrespective of confounding factors, such as age, gender,
      smoking status, alcohol consumption, physical activity, income, and education
      (MHO; 6.73+/-0.05, MAO; 6.82+/-0.05, MHNW; 6.94+/-0.04, and MANW; 6.91+/-0.05; P
      <0.001). CONCLUSION: Sleep duration is independently associated with body size
      phenotype after adjusting for confounding factors in the Korean population.

PMID- 25573818
TI  - Retained versus resected posterior cruciate ligament in mobile-bearing total knee
      replacement: a retrospective, clinical and functional assessment.
AB  - PURPOSE: Fully conforming, mobile-bearing total knee replacement (TKR) was
      initially designed using a posterior cruciate-sacrificing (CS) technique.
      Rotating-platform TKR that could also be performed retaining the posterior
      cruciate developed afterwards. The purpose of this study was to compare the
      clinical and functional outcomes of patients who had either cruciate-retaining
      (CR) or cruciate-sacrificing (CS) TKR at a minimum follow-up of 2 years with the
      same prosthetic design. METHODS: One hundred and two consecutive TKR (88
      patients) were performed at the same institution either with CS (56 TKR-49
      patients) or with CR (46 TKR-39 patients) technique. Patients were followed at a
      minimum of 2 years. Patients were evaluated for articular range of motion,
      complication rate (infection, loosening) and clinical outcome measures included
      the pain and functional components of the Knee Society Score. RESULTS: The two
      groups (CS, CR) were homogeneous. At final follow-up, no significant difference
      was seen between the two surgical techniques in terms of ROM, pain and functional
      level, and revision rate. CONCLUSIONS: This study showed that for this given
      mobile-bearing, fully conforming prosthetic design, sacrificing or resecting the
      PCL does not influence the clinical and functional outcomes at a minimum of 2
      year follow-up. Surgeons may indifferently choose one of the two options (CS, CR)
      according to their preferences. LEVEL OF EVIDENCE: Case series, level IV.

PMID- 25573819
TI  - Vascular endothelial growth factor-dependent angiogenesis and dynamic vascular
      plasticity in the sensory circumventricular organs of adult mouse brain.
AB  - The sensory circumventricular organs (CVOs), which comprise the organum
      vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO) and the
      area postrema (AP), lack a typical blood-brain barrier (BBB) and monitor directly
      blood-derived information to regulate body fluid homeostasis, inflammation,
      feeding and vomiting. Until now, almost nothing has been documented about
      vascular features of the sensory CVOs except fenestration of vascular endothelial
      cells. We therefore examine whether continuous angiogenesis occurs in the sensory
      CVOs of adult mouse. The angiogenesis-inducing factor vascular endothelial growth
      factor-A (VEGF-A) and the VEGF-A-regulating transcription factor hypoxia
      inducible factor-1alpha were highly expressed in neurons of the OVLT and SFO and
      in both neurons and astrocytes of the AP. Expression of the pericyte-regulating
      factor platelet-derived growth factor B was high in astrocytes of the sensory
      CVOs. Immunohistochemistry of bromodeoxyuridine and Ki-67, a nuclear protein that
      is associated with cellular proliferation, revealed active proliferation of
      endothelial cells. Moreover, immunohistochemistry of caspase-3 and the basement
      membrane marker laminin showed the presence of apoptosis and sprouting of
      endothelial cells, respectively. Treatment with the VEGF receptor-associated
      tyrosine kinase inhibitor AZD2171 significantly reduced proliferation and
      filopodia sprouting of endothelial cells, as well as the area and diameter of
      microvessels. The mitotic inhibitor cytosine-b-D-arabinofuranoside reduced
      proliferation of endothelial cells and the vascular permeability of blood-derived
      low-molecular-weight molecules without changing vascular area and microvessel
      diameter. Thus, our data indicate that continuous angiogenesis is dependent on
      VEGF signaling and responsible for the dynamic plasticity of vascular structure
      and permeability. 

PMID- 25573821
TI  - Erection pattern and section-wise wettability of honeybee glossal hairs in nectar
      feeding.
AB  - The honeybee's tongue (glossa) is covered with bushy hairs and resembles a mop or
      a brush. We examined the dimensions of glossal hairs of the Italian honeybee
      (Apis mellifera ligustica) and found that the average length of hairs increased
      from the proximal segment to the distal end. The glossal dynamic surface of a
      honeybee in drinking cycles was captured by a specially designed high-speed
      camera system, and we discovered that the glossal hairs erected rhythmically when
      drinking nectar; specifically, hairs on the proximal segment erected earlier than
      those on the distal end of a honeybee's tongue, which was identified as the
      phenomenon of asynchronous hair erection. Moreover, by measuring the wettability
      of the tongue, we found that the flabellum was the most hydrophilic and the root
      of the tongue was hardest to be wetted. According to our observations, we suggest
      that the honeybee has an optimal hair-erection pattern that could balance nectar
      intake and viscous drag. These results will be helpful to understand the liquid
      feeding mechanism of honeybees, especially the role of erectable glossal hairs. 

PMID- 25573820
TI  - Middle-term results of trans-catheter creation of atrial communication in
      patients receiving mechanical circulatory support.
AB  - OBJECTIVE: To describe our center's middle-term outcomes following trans-catheter
      creation of atrial communication (ASD) in patients on mechanical circulatory
      support. BACKGROUND: Trans-catheter creation of an ASD in patients on mechanical
      circulatory support is an adjuvant therapy to reduce left atrial pressure and
      associated morbidity. Data on middle term outcomes following this procedure,
      specifically in regards to the fate of the ASD, are limited. METHODS:
      Retrospective observational study of consecutive children and adults undergoing
      trans-catheter creation of an atrial septal communication between 1/1/2006 and
      5/1/2014, reviewing their baseline characteristics, procedural details, and data
      from follow-up. RESULTS: Over the study period, 37/227 (16%) subjects undergoing
      veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) underwent trans
      catheter creation of an atrial communication. Mortality on VA-ECMO support in
      this subgroup was 19%, with an additional 24% transitioning to ventricular assist
      device. Of the 57% who survived to separation from VA-ECMO, 16/21 (76%) had
      residual atrial communications. 56% of these underwent closure procedures.
      CONCLUSIONS: Following trans-catheter creation of ASD, a residual ASD is present
      in the majority of assessable survivors and represents a potential volume
      overload and/or right to left shunt that may need to be addressed.

PMID- 25573822
TI  - Functional characterisation of the chromatically antagonistic photosensitive
      mechanism of erythrophores in the tilapia Oreochromis niloticus.
AB  - Non-visual photoreceptors with diverse photopigments allow organisms to adapt to
      changing light conditions. Whereas visual photoreceptors are involved in image
      formation, non-visual photoreceptors mainly undertake various non-image-forming
      tasks. They form specialised photosensory systems that measure the quality and
      quantity of light and enable appropriate behavioural and physiological responses.
      Chromatophores are dermal non-visual photoreceptors directly exposed to light and
      they not only receive ambient photic input but also respond to it. These
      specialised photosensitive pigment cells enable animals to adjust body coloration
      to fit environments, and play an important role in mate choice, camouflage and
      ultraviolet (UV) protection. However, the signalling pathway underlying
      chromatophore photoresponses and the physiological importance of chromatophore
      colour change remain under-investigated. Here, we characterised the intrinsic
      photosensitive system of red chromatophores (erythrophores) in tilapia. Like some
      non-visual photoreceptors, tilapia erythrophores showed wavelength-dependent
      photoresponses in two spectral regions: aggregations of inner pigment granules
      under UV and short-wavelengths and dispersions under middle- and long
      wavelengths. The action spectra curve suggested that two primary photopigments
      exert opposite effects on these light-driven processes: SWS1 (short-wavelength
      sensitive 1) for aggregations and RH2b (rhodopsin-like) for dispersions. Both
      western blot and immunohistochemistry showed SWS1 expression in integumentary
      tissues and erythrophores. The membrane potential of erythrophores depolarised
      under UV illumination, suggesting that changes in membrane potential are required
      for photoresponses. These results suggest that SWS1 and RH2b play key roles in
      mediating intrinsic erythrophore photoresponses in different spectral ranges and
      this chromatically dependent antagonistic photosensitive mechanism may provide an
      advantage to detect subtle environmental photic change. 

PMID- 25573823
TI  - Vasotocin and isotocin regulate aquaporin 1 function in the sea bream.
AB  - Aquaporins (AQPs) are specific transmembrane water channels with an important
      function in water homeostasis. In terrestrial vertebrates, AQP2 function is
      regulated by vasopressin (AVP) to accomplish key functions in osmoregulation. The
      endocrine control of aquaporin function in teleosts remains little studied.
      Therefore, in this study we investigated the regulatory role of vasotocin (AVTR)
      and isotocin (ITR) receptors in Aqp1 paralog gene function in the teleost
      gilthead sea bream (Sparus aurata). The complete coding regions of Aqp1a, Aqp1b,
      AVTR V1a2-type, AVTR V2-type and ITR from sea bream were isolated. A Xenopus
      oocyte-swelling assay was used to functionally characterize AQP1 function and
      regulation by AVT and IT through their cognate receptors. Microinjection of
      oocytes with Aqp1b mRNA revealed regulation of water transport via PKA
      (IBMX+forskolin sensitive), whereas Aqp1a mRNA injection had the same effect via
      PKC signaling (PDBU sensitive). In the absence of expressed receptors, AVT and IT
      (10(-8) mol l(-1)) were unable to modify AQP1 function. AVT regulated AQP1a and
      AQP1b function only when the AVTR V2-type was co-expressed. IT regulated AQP1a
      function, but not AQP1b, only when ITR was present. Considering that Aqp1a and
      Aqp1b gene expression in the sea bream intestine is highly salinity dependent in
      vivo, our results in ovo demonstrate a regulatory role for AVT and IT in AQP1
      function in the sea bream in the processing of intestinal fluid to achieve
      osmoregulation. 

PMID- 25573824
TI  - Mechanical challenges to freshwater residency in sharks and rays.
AB  - Major transitions between marine and freshwater habitats are relatively
      infrequent, primarily as a result of major physiological and ecological
      challenges. Few species of cartilaginous fish have evolved to occupy freshwater
      habitats. Current thought suggests that the metabolic physiology of sharks has
      remained a barrier to the diversification of this taxon in freshwater ecosystems.
      Here, we demonstrate that the physical properties of water provide an additional
      constraint for this species-rich group to occupy freshwater systems. Using
      hydromechanical modeling, we show that occurrence in fresh water results in a two
      to three-fold increase in negative buoyancy for sharks and rays. This carries
      the energetic cost of lift production and results in increased buoyancy-dependent
      mechanical power requirements for swimming and increased optimal swim speeds. The
      primary source of buoyancy, the lipid-rich liver, offers only limited
      compensation for increased negative buoyancy as a result of decreasing water
      density; maintaining the same submerged weight would involve increasing the liver
      volume by very large amounts: 3- to 4-fold in scenarios where liver density is
      also reduced to currently observed minimal levels and 8-fold without any changes
      in liver density. The first data on body density from two species of elasmobranch
      occurring in freshwater (the bull shark Carcharhinus leucas, Muller and Henle
      1839, and the largetooth sawfish Pristis pristis, Linnaeus 1758) support this
      hypothesis, showing similar liver sizes as marine forms but lower liver
      densities, but the greatest negative buoyancies of any elasmobranch studied to
      date. Our data suggest that the mechanical challenges associated with buoyancy
      control may have hampered the invasion of freshwater habitats in elasmobranchs,
      highlighting an additional key factor that may govern the predisposition of
      marine organisms to successfully establish in freshwater habitats.

PMID- 25573825
TI  - Selection for upper thermal tolerance in rainbow trout (Oncorhynchus mykiss
      Walbaum).
AB  - Rainbow trout (Oncorhynchus mykiss Walbaum) in southern Western Australia have
      undergone passive selection for over 19 generations to survive high water
      temperatures. Based on the conceptual model of 'oxygen- and capacity-limited
      thermal tolerance', we measured critical thermal maximum (CTmax), maximum heart
      rate (fH,max) and aerobic scope to test the hypothesis that these rainbow trout
      can maintain aerobic scope at high temperatures through a robust cardiac
      performance supporting oxygen delivery. Across five family groups CTmax averaged
      29.0+/-0.02 degrees C. Aerobic scope was maximized at 15.8+/-0.3 degrees C
      (Topt), while the upper pejus temperature (Tpej, set at 90% of maximum aerobic
      scope) was 19.9+/-0.3 degrees C. Although aerobic scope decreased at temperatures
      above Topt, the value at 25 degrees C remained well over 40% of the maximum.
      Furthermore, pharmacologically stimulated fH,max increased with temperature,
      reaching a peak value between 23.5+/-0.4 and 24.0+/-0.4 degrees C (Tmax) for
      three family groups. The Arrhenius breakpoint temperature (TAB) for fH,max was
      20.3+/-0.3 to 20.7+/-0.4 degrees C, while the average Q10 breakpoint temperature
      (TQB, when the incremental Q10<1.6) for fH,max was 21.6+/-0.2 to 22.0+/-0.4
      degrees C. Collectively, fH,max progressively became less temperature dependent
      beyond 20 degrees C (TAB and TQB), which coincides with the upper Tpej for
      aerobic scope. Although upper thermal performance indices for both aerobic scope
      and fH,max were compared among family groups in this population, appreciable
      differences were not evident. Compared with other populations of rainbow trout,
      the present assessment is consistent with the prediction that this strain has
      undergone selection and shows the ability to tolerate higher water temperatures. 

PMID- 25573826
TI  - Shiver me titin! Elucidating titin's role in shivering thermogenesis.
AB  - Shivering frequency scales predictably with body mass and is 10 times higher in a
      mouse than a moose. The link between shivering frequency and body mass may lie in
      the tuning of muscle elastic properties. Titin functions as a muscle 'spring', so
      shivering frequency may be linked to titin's structure. The muscular dystrophy
      with myositis (mdm) mouse is characterized by a deletion in titin's N2A region.
      Mice that are homozygous for the mdm mutation have a lower body mass, stiffer
      gait and reduced lifespan compared with their wild-type and heterozygous
      siblings. We characterized thermoregulation in these mice by measuring metabolic
      rate and tremor frequency during shivering. Mutants were heterothermic at ambient
      temperatures of 20-37 degrees C while wild-type and heterozygous mice were
      homeothermic. Metabolic rate increased at smaller temperature differentials (i.e.
      the difference between body and ambient temperatures) in mutants than in non
      mutants. The difference between observed tremor frequencies and shivering
      frequencies predicted by body mass was significantly larger for mutant mice than
      for wild-type or heterozygous mice, even after accounting for differences in body
      temperature. Together, the heterothermy in mutants, the increase in metabolic
      rate at low temperature differentials and the decreased tremor frequency
      demonstrate the thermoregulatory challenges faced by mice with the mdm mutation.
      Oscillatory frequency is proportional to the square root of stiffness, and we
      observed that mutants had lower active muscle stiffness in vitro. The lower
      tremor frequencies in mutants are consistent with reduced active muscle stiffness
      and suggest that titin affects the tuning of shivering frequency. 

PMID- 25573827
TI  - Safety of Immunomodulators and Anti-TNF Therapy in Pregnancy.
AB  - OPINION STATEMENT: Biologics have proved to be extremely effective therapies for
      active, difficult to treat ulcerative colitis and Crohn's disease. Given that
      active disease appears to be what drives worse outcomes in conception and
      pregnancy, understanding of the potential risks of continued biologic therapy
      during pregnancy is important. Knowledge of the mechanisms of placental transfer
      helps clinicians explain to patients the timing of potential cessation of
      therapy, and the ongoing data collection from the efforts of the Crohn's and
      Colitis Pregnancy Registry have helped immensely to move this field forward. The
      body of evidence for use of thiopurines as well has supported their continued use
      during pregnancy in patients, despite their category D rating. Family planning
      and counseling have come a long way with our efforts in understanding that the
      real enemy is active inflammation, not the therapies we use to treat it.

PMID- 25573828
TI  - Palladin is upregulated in kidney disease and contributes to epithelial cell
      migration after injury.
AB  - Recovery from acute kidney injury involving tubular epithelial cells requires
      proliferation and migration of healthy cells to the area of injury. In this
      study, we show that palladin, a previously characterized cytoskeletal protein, is
      upregulated in injured tubules and suggest that one of its functions during
      repair is to facilitate migration of remaining cells to the affected site. In a
      mouse model of anti-neutrophilic cytoplasmic antibody involving both tubular and
      glomerular disease, palladin is upregulated in injured tubular cells, crescents
      and capillary cells with angiitis. In human biopsies of kidneys from patients
      with other kidney diseases, palladin is also upregulated in crescents and injured
      tubules. In LLC-PK1 cells, a porcine proximal tubule cell line, stress induced by
      transforming growth factor-beta1 (TGF-beta1) leads to palladin upregulation.
      Knockdown of palladin in LLC-PK1 does not disrupt cell morphology but does lead
      to a defect in cell migration. Furthermore, TGF-beta1 induced increase in the 75
      kDa palladin isoform occurs in both the nucleus and the cytoplasm. These data
      suggest that palladin expression is induced in injured cells and contributes to
      proper migration of cells in proximal tubules, possibly by regulation of gene
      expression as part of the healing process after acute injury.

PMID- 25573829
TI  - Acute heart failure in the elderly: differences in clinical characteristics,
      outcomes, and prognostic factors in the VERITAS Study.
AB  - BACKGROUND: Acute heart failure (HF) is common in the elderly, but the
      association of age with clinical outcomes and prognostic factors has not been
      examined thoroughly. METHODS AND RESULTS: We analyzed the clinical and laboratory
      characteristics and the outcomes of 1,347 patients with acute HF enrolled in the
      VERITAS trial. Subjects were subdivided based on their median age of 72 years.
      Older patients had a higher prevalence of comorbidities and a higher prevalence
      of hypertension and atrial fibrillation. During a mean follow-up of 149 +/- 61
      days, 432 patients (32.1%) reached the composite end point of death, in-hospital
      worsening HF, or HF rehospitalization by 30 days, and 135 patients (10.4%) died
      by 90 days, with a worse outcome in elderly patients in both cases. At
      multivariable analysis, different variables were related with each of these
      outcomes in elderly compared with younger patients. Regarding deaths at 90 days,
      plasma urea nitrogen and hemoglobin levels were predictive only in the younger
      patients, whereas respiratory rate and albumin levels were associated with
      mortality only in the older patients. CONCLUSIONS: Elderly patients with acute HF
      have different clinical characteristics and poorer outcomes. Prognostic variables
      differ in elderly compared with younger patients.

PMID- 25573832
TI  - Letter to the Editor regarding article by Hussein et al. doi:10.1007/s00405-014
      3309-7.

PMID- 25573833
TI  - Response to the letter to the editor regarding article by Hussein et al. DOI:
      10.1007/s00405-014-3309-7.

PMID- 25573830
TI  - Decreases in daily physical activity predict acute decline in attention and
      executive function in heart failure.
AB  - BACKGROUND: Reduced physical activity (PA) may be one factor that contributes to
      cognitive decline and dementia in heart failure (HF). Yet, the longitudinal
      relationship between PA and cognition in HF is poorly understood owing to
      limitations of past work, including single-time assessments of PA. This is the
      first study to examine changes in objectively measured PA and cognition over time
      in HF. METHODS AND RESULTS: At baseline and 12 weeks, 57 HF patients completed
      psychosocial self-report measures and a neuropsychological battery and wore an
      accelerometer for 7 days. At baseline, HF patients spent an average of 597.83 (SD
      75.91) minutes per day sedentary. Steps per day declined from baseline to the 12
      week follow-up; there was also a trend for declines in moderate-vigorous PA.
      Regression analyses controlling for sex, HF severity, and depressive symptoms
      showed that decreases in light (P = .08) and moderate-vigorous (P = .04) daily PA
      emerged as strong predictors of declines in attention/executive function over the
      12-week period, but not of memory or language. CONCLUSIONS: Reductions in daily
      PA predicted acute decline in attention/executive function in HF, but not of
      memory or language. Modifications to daily PA may attenuate cognitive decline,
      and prospective studies are needed to test this possibility.

PMID- 25573834
TI  - Endpoints and cutpoints in head and neck oncology trials: methodical background,
      challenges, current practice and perspectives.
AB  - This article reviews the methodical and statistical basics of designing a trial,
      with a special focus on the process of defining and choosing endpoints and
      cutpoints as the foundations of clinical research, and ultimately that of
      evidence-based medicine. There has been a significant progress in the treatment
      of head and neck cancer in the past few decades. Currently available treatment
      options can have a variety of different goals, depending e.g. on tumor stage,
      among other factors. The outcome of a specific treatment in clinical trials is
      measured using endpoints. Besides classical endpoints, such as overall survival
      or organ preservation, other endpoints like quality of life are becoming
      increasingly important in designing and conducting a trial. The present work is
      based on electronic research and focuses on the solid methodical and statistical
      basics of a clinical trial, on the structure of study designs and on the
      presentation of various endpoints.

PMID- 25573831
TI  - Prognostic value of aldosterone and cortisol in patients hospitalized for acutely
      decompensated chronic heart failure with and without mineralocorticoid receptor
      antagonism.
AB  - BACKGROUND: Serum aldosterone and cortisol independently predict an increased
      mortality risk in heart failure (HF), and mineralocorticoid receptor antagonism
      (MRA) improves survival. The prognostic relevance of aldosterone and cortisol
      with MRA is unclear. METHODS AND RESULTS: In this post hoc analysis of a
      prospective cohort, study serum levels of aldosterone and cortisol were measured
      at baseline in 842 patients with systolic HF. The mean age was 68 +/- 12 years
      (27% female, 45% in New York Heart Association functional class III/IV, 43% with
      MRA; median follow-up 38 months [interquartile range 30-43 mo]). Crude mortality
      in the total cohort was 43% (patients with vs without MRA: 34% vs 41%; P = .052).
      In MRA-naive patients, higher levels of both aldosterone and cortisol were
      predictive of increased mortality risk in multivariable Cox regression: hazard
      ratio (HR) with 95% confidence interval of highest vs lowest tertile for
      aldosterone: 1.51 [1.02-2.24] (P = .040); and for cortisol: 1.94 [1.28-2.93] (P =
      .002). In MRA-treated patients, aldosterone (highest vs lowest tertile: HR 1.65
      [1.01-2.71]; P = .048) but not cortisol (HR 0.77 [0.44-1.27]; P = .33) was
      associated with all-cause mortality. Further subgroup analysis revealed that
      particularly patients with low cortisol and high aldosterone levels had the worst
      prognosis (HR 5.01 [2.22-11.3]; P < .001), compared with the reference of low
      cortisol and low aldosterone. Subjects with this profile had larger ventricles
      and more often coronary artery disease. CONCLUSIONS: In systolic HF, the
      prognostic value of aldosterone and cortisol levels differs in dependency of MRA
      intake. The pathophysiologic link between low cortisol, high aldosterone, and
      increased mortality risk in patients with MRA needs to be clarified.

PMID- 25573835
TI  - Nasal and oral snoring endoscopy: novel and promising diagnostic tools in OSAS
      patients.
AB  - The aim of the present study was to investigate if any of the three awake
      procedures [fiberoptic nasopharyngoscopy with modified Muller Maneuver (FNMM),
      nasal snoring endoscopy (NSE), or oral snoring endoscopy (OSE)] could efficiently
      predict the grade or pattern of upper airway (UA) collapse found with drug
      induced sleep endoscopy (DISE), which is considered by many authors as the
      current gold standard in optimizing obstructive sleep apnea syndrome (OSAS)
      patient selection for UA surgery. Twenty consecutive patients (simple snorers and
      OSAS patients) were studied with FNMM, NSE, OSE, and DISE. The inter-test
      agreement was evaluated with Cohen's kappa coefficient (kappa). In the current
      series, we found that NSE and OSE were better than FNMM in predicting the pattern
      of collapse found with DISE. A significant pattern agreement between NSE and DISE
      was present in all sub-sites, and the agreement was measured with a scale
      proposed by Landis and Koch as: moderate in velo- and oropharynx (kappa = 0.52, p
      = 0.001, and kappa = 0.47, p = 0.003, respectively), and substantial in
      hypopharynx (kappa = 0.63, p < 0.00001). Comparing OSE with DISE, the pattern
      agreement was almost perfect at oropharyngeal level (kappa = 0.82, p < 0.00001),
      and moderate at hypopharyngeal level (kappa = 0.55, p = 0.0002); while a trend
      towards significance was found at velopharyngeal level (kappa = 0.20, p = 0.07).
      FNMM showed a fair pattern agreement with DISE only at oropharyngeal level (kappa
      = 0.31, p = 0.009); while in the other sub-sites, no significant agreement was
      found. NSE and OSE are new promising diagnostic tools in OSAS patients. Further
      investigations are needed to see if they could predict the effectiveness of UA
      surgery.

PMID- 25573836
TI  - Significance of CYCLOOXYGENASE-2(COX-2), PERIOSTIN (POSTN) and INTERLEUKIN-4(IL
      4) gene expression in the pathogenesis of chronic rhinosinusitis with nasal
      polyps.
AB  - The purpose of this paper was to evaluate the level of Cyclooxygenase-2 (COX-2),
      Periostin (POSTN) and Interleukin-4(IL-4) gene expression in patients with
      chronic rhinosinusitis with nasal polyps, without polyps and with a nasal septum
      deviation. The tests were performed on 63 patients (24 women and 39 men) with
      chronic rhinosinusitis and polyps (CRSwP-study group I), with determination of
      the COX-2, POSTN and IL-4 gene expression; an allergy was diagnosed in 38 cases.
      The reference groups were patients with chronic rhinosinusitis without polyps-
      CRS (n = 23, including 14 women and 9 men) and patients with nasal septum
      deviation--DSN (n = 18, including 9 women and 9 men). The expression level was
      determined in the polyp tissue and the mucosa of paranasal sinus collected during
      an FESS. The expression level of studied genes was also evaluated in the
      material. Immediately after being collected, the tissue fragments were placed in
      test tubes with 1 ml of RNAlater (Qiagen, Hilden, Germany) preventing the
      degradation of RNA and frozen at -70  degrees C. The studies revealed an
      increased level of POSTN, IL-4 gene expression and a decreased level of COX-2
      gene expression that may be associated with the development of chronic
      rhinosinusitis with nasal polyps. An analysis of the expression level indicates
      the participation of POSTN and IL-4 in the development of chronic rhinosinusitis
      with nasal polyps in patients with atopy.

PMID- 25573837
TI  - Increased risk of tinnitus in patients with temporomandibular disorder: a
      retrospective population-based cohort study.
AB  - This study determined whether there is an increased risk of tinnitus in patients
      with temporomandibular joint (TMJ). We used information from health insurance
      claims obtained from Taiwan National Health Insurance (TNHI). Patients aged 20
      years and older who were newly diagnosed with TMJ disorder served as the study
      cohort. The demographic factors and comorbidities that may be associated with
      tinnitus were also identified, including age, sex, and comorbidities of hearing
      loss, noise effects on the inner ear, and degenerative and vascular ear
      disorders. A higher proportion of TMJ disorder patients suffered from hearing
      loss (5.30 vs. 2.11 %), and degenerative and vascular ear disorders (0.20 vs.
      0.08 %) compared with the control patients. The crude hazard ratio (HR) of
      tinnitus in the TMJ disorder cohort was 2.73-fold higher than that in the control
      patients, with an adjusted HR of 2.62 (95 % CI = 2.29-3.00). The comorbidity
      specific TMJ disorder cohort to the control patients' adjusted HR of tinnitus was
      higher for patients without comorbidity (adjusted HR = 2.75, 95 % CI = 2.39
      3.17). We also observed a 3.22-fold significantly higher relative risk of
      developing tinnitus within the 3-year follow-up period (95 % CI = 2.67-3.89).
      Patients with TMJ disorder might be at increased risk of tinnitus.

PMID- 25573838
TI  - Postoperative hyperbilirubinemia suggests the occurrence of complications after
      esophagectomy for esophageal cancer.
AB  - BACKGROUND: Serum bilirubin levels frequently increase after esophagectomy for
      esophageal cancer. Several studies have reported hyperbilirubinemia in patients
      with postoperative complications. We aimed to perform a detailed large-scale
      analysis to clarify this association. METHODS: We compared postoperative serum
      bilirubin levels of 200 patients with esophageal cancer who underwent
      esophagectomy, with and without postoperative complications, from January 2008 to
      July 2013 at Keio University Hospital, Tokyo, Japan. We also analyzed other risk
      factors for postoperative hyperbilirubinemia by univariate and multivariate
      analyses in an attempt to determine the mechanism of postoperative
      hyperbilirubinemia. RESULTS: Hyperbilirubinemia (total bilirubin >2.0 mg/dL)
      occurred in 71 patients (35.5 %). The mean total bilirubin peak level was 1.5
      mg/dL in patients without complications, 2.0 mg/dL in those with at least one
      complication, 2.1 mg/dL in those with pneumonia, and 2.3 mg/dL in those with
      anastomotic leakage. Bilirubin levels were significantly higher in each
      complication group than in the non-complication group (p < 0.05 for all). Risk
      factors of postoperative hyperbilirubinemia by univariate analysis were the
      preoperative bilirubin level, video-assisted thoracoscopic surgery, three-field
      lymph node dissection, thoracic duct resection, prolonged surgical duration,
      severe complications (Clavien-Dindo grade >=3), and severe anastomotic leakage
      (Clavien-Dindo grade >=3). In contrast, the pT factor and postoperative enteral
      nutrition were negatively associated with postoperative hyperbilirubinemia. Risk
      factors by multivariate analysis were the preoperative bilirubin level, prolonged
      surgical duration, severe complications, and postoperative enteral nutrition.
      CONCLUSIONS: Although various factors impact postoperative hyperbilirubinemia,
      postoperative complications were most significantly associated with postoperative
      hyperbilirubinemia. Patients with postoperative hyperbilirubinemia after
      esophagectomy must be managed more carefully because unnoticed complications may
      be associated with hyperbilirubinemia.

PMID- 25573840
TI  - Cost-effectiveness of TNF inhibitors vs synthetic disease-modifying antirheumatic
      drugs in patients with rheumatoid arthritis: a Markov model study based on two
      longitudinal observational studies.
AB  - OBJECTIVE: The objective of this study was to estimate the additional costs and
      health benefits of adding a TNF inhibitor (TNFi) (adalimumab, certolizumab,
      etanercept, golimumab, infliximab) to a synthetic DMARD (sDMARD), e.g. MTX, in
      patients with RA. METHODS: We developed the Norwegian RA model as a Markov model
      simulating 10 years of treatment with either TNFi plus sDMARDs (TNFi strategy) or
      sDMARDs alone (synthetic strategy). Patients in both strategies started in one of
      seven health states, based on the Short Form-6 Dimensions (SF-6D). The patients
      could move to better or worse health states according to transition
      probabilities. In the TNFi strategy, patients could stay on TNFi (including
      switch of TNFi), or switch to non-TNFi-biologics (abatacept, rituximab,
      tocilizumab), sDMARDs or no DMARD. In the synthetic strategy, patients remained
      on sDMARDs. Data from two observational studies were used for the assessment of
      resource use and utilities in the health states. Health benefits were evaluated
      using the EuroQol-5 Dimensions (EQ-5D) and SF-6D. RESULTS: The Norwegian RA model
      predicted that 10-year discounted health care costs totalled ?124,942 (?475,266
      including production losses) for the TNFi strategy and ?65,584 (?436,517) for the
      synthetic strategy. The cost per additionally gained quality-adjusted life-year
      of adding a TNFi was ?92,557 (?60,227 including production losses) using SF-6D
      and ?61,285 (?39,841) using EQ-5D. Including health care costs only, the
      probability that TNFi treatment was cost-effective was 90% when using EQ-5D,
      assuming a Norwegian willingness-to-pay level of ?67,300. CONCLUSION: TNFi
      treatment for RA is cost-effective when accounting for production losses.
      Excluding production losses, TNFi treatment is cost-effective using EQ-5D, but
      not SF-6D.

PMID- 25573842
TI  - What is public health?

PMID- 25573843
TI  - Tributes to Professor Walter Patrick.

PMID- 25573841
TI  - Rituximab in diffuse cutaneous systemic sclerosis: should we be using it today?
AB  - There is new evidence that B-cell depletion could be an effective intervention in
      patients with SSc. Observational case-control study data from the European League
      Against Rheumatism Scleroderma Trials and Research group has suggested that
      rituximab therapy may reduce progression of skin thickening and lung fibrosis,
      especially in a subgroup with early dcSSc. These positive data remain preliminary
      and need to be viewed with caution, recognizing the spontaneous regression of
      skin thickening that may occur during early disease. In this review, we summarize
      the clinical evidence for the therapeutic use of rituximab in SSc as well as the
      basic science evidence suggesting that B cells and autoantibodies are the primary
      drivers of fibrosis in skin and lung tissue. We have also reviewed the parallels
      between SSc and the other CTDs where B-cell depletion therapy is efficacious.

PMID- 25573839
TI  - Improved prediction of knee osteoarthritis progression by genetic polymorphisms:
      the Arthrotest Study.
AB  - OBJECTIVE: The aim of this study was to develop a genetic prognostic tool to
      predict radiographic progression towards severe disease in primary knee OA (KOA)
      patients. METHODS: This investigation was a cross-sectional, retrospective,
      multicentric association study in 595 Spanish KOA patients. Caucasian patients
      aged >=40 years at the time of diagnosis of primary KOA of Kellgren-Lawrence
      grade 2 or 3 were included. Patients who progressed to Kellgren-Lawrence score 4
      or who were referred for total knee replacement within 8 years after diagnosis
      were classified as progressors to severe disease. Clinical variables of the
      initial stages of the disease (gender, BMI, age at diagnosis, OA in the
      contralateral knee, and OA in other joints) were registered as potential
      predictors. Single nucleotide polymorphisms and clinical variables with an
      association of P < 0.05 were included in the multivariate analysis using forward
      logistic regression. RESULTS: A total of 23 single nucleotide polymorphisms and
      the time of primary KOA diagnosis were significantly associated with KOA severe
      progression in the exploratory cohort (n = 220; P < 0.05). The predictive
      accuracy of the clinical variables was limited: area under the curve (AUC) =
      0.66. When genetic variables were added to the clinical model (full model), the
      prediction of KOA progression was significantly improved (AUC = 0.82). Combining
      only genetic variables (rs2073508, rs10845493, rs2206593, rs10519263, rs874692,
      rs7342880, rs780094 and rs12009), a predictive model with good accuracy was also
      obtained (AUC = 0.78). The predictive ability for KOA progression of the full
      model was confirmed on the replication cohort (two-sample Z-test; n = 62; P =
      0.190). CONCLUSION: An accurate prognostic tool to predict primary KOA
      progression has been developed based on genetic and clinical information from OA
      patients.

PMID- 25573844
TI  - Integrating the Principles of Effective Intervention into Batterer Intervention
      Programming: The Case for Moving Toward More Evidence-Based Programming.
AB  - The majority of batterer intervention program (BIP) evaluations have indicated
      they are marginally effective in reducing domestic violence recidivism.
      Meanwhile, correctional programs used to treat a variety of offenders (e.g.,
      substance users, violent offenders, and so forth) that adhere to the "principles
      of effective intervention" (PEI) have reported significant reductions in
      recidivism. This article introduces the PEI-the principles on which evidence
      based practices in correctional rehabilitation are based-and identifies the
      degree to which they are currently integrated into BIPs. The case is made that
      batterer programs could be more effective if they incorporate the PEI.
      Recommendations for further integration of the principles into BIPs are also
      provided. 

PMID- 25573845
TI  - Rethinking Conceptual Definitions of the Criminal Career and Serial Criminality.
AB  - Since Cesare Lombroso's days, criminology seeks to define, explain, and
      categorize the various types of criminals, their behaviors, and motives. This aim
      has theoretical as well as policy-related implications. One of the important
      areas in criminological thinking focuses chiefly on recidivist offenders who
      perform large numbers of crimes and/or commit the most dangerous crimes in
      society (rape, murder, arson, and armed robbery). These criminals have been
      defined as "habitual offenders," "professional criminals," "career criminals,"
      and "serial offenders." The interest in these criminals is a rational one, given
      the perception that they present a severe threat to society. The main challenge
      in this area of research is a conceptual problem that has significant effects
      across the field. To this day, scholars have reused and misused titles to define
      and explain different concepts. The aim of this article is 3-fold. First, to
      review the concepts of criminal career, professional crime, habitual offenses,
      and seriality with a critical attitude on confusing terms. Second, to propose the
      redefinition of concepts mentioned previously, mainly on the criminal career.
      Third, to propose a theoretical model to enable a better understanding of, and
      serve as a basis for, further research in this important area of criminology. 

PMID- 25573846
TI  - Effects of Parenting Programs on Child Maltreatment Prevention: A Meta-Analysis.
AB  - The objective of this study is to evaluate the effectiveness of parenting
      programs in reducing child maltreatment and modifying associated factors as well
      as to examine the moderator variables that are linked to program effects. For
      this meta-analysis, we searched nine electronic databases to identify randomized
      controlled trials published before September 2013. The effect sizes of various
      outcomes at different time points were computed. From the 3,578 studies
      identified, we selected 37 studies for further analysis. The total random effect
      size was 0.296. Our results showed that parenting programs successfully reduced
      substantiated and self-reported child maltreatment reports and reduced the
      potential for child maltreatment. The programs also reduced risk factors and
      enhanced protective factors associated with child maltreatment. However, the
      effects of the parenting programs on reducing parental depression and stress were
      limited. Parenting programs produced positive effects in low-, middle-, and high
      income countries and were effective in reducing child maltreatment when applied
      as primary, secondary, or tertiary child maltreatment intervention. In
      conclusion, parenting programs are effective public health approaches to reduce
      child maltreatment. The evidence-based service of parenting programs could be
      widely adopted in future practice. 

PMID- 25573847
TI  - Enantioselective organocatalytic reduction of beta-trifluoromethyl nitroalkenes:
      an efficient strategy for the synthesis of chiral beta-trifluoromethyl amines.
AB  - An efficient organocatalytic stereoselective reduction of beta-trifluoromethyl
      substituted nitroalkenes, mediated by 3,5-dicarboxylic ester-dihydropyridines
      (Hantzsch ester type), has been successfully developed. A multifunctional
      thiourea-based (S)-valine derivative was found to be the catalyst of choice,
      promoting the reaction in up to 97% ee. The methodology has been applied to a
      wide variety of substrates, leading to the formation of differently substituted
      precursors of enantiomerically enriched beta-trifluoromethyl amines. The
      mechanism of the reaction and the mode of action of the metal-free catalytic
      species were computationally investigated; on the basis of DFT transition-state
      (TS) analysis, a model of stereoselection was also proposed.

PMID- 25573848
TI  - New-onset atrial fibrillation in sepsis is associated with increased morbidity
      and mortality.
AB  - BACKGROUND: The development of new-onset atrial fibrillation in sepsis has been
      associated with adverse outcomes. METHODS: A systematic literature search was
      conducted to retrieve articles that investigated the association of new-onset
      atrial fibrillation in patients diagnosed with sepsis. The primary outcome of
      interest was the pooled risk ratio (RR) of in-hospital mortality in patients with
      new-onset atrial fibrillation and sepsis. RESULTS: Six studies included 3100
      patients with new-onset atrial fibrillation in sepsis and 36,900 patients without
      new-onset atrial fibrillation in sepsis. The pooled RR for in-hospital mortality
      was 1.45 (95 % CI 1.32-1.60, p < 0.00001, I (2 = )24 %). New-onset atrial
      fibrillation was also associated with increased ICU mortality, ICU and in
      hospital length of stay and stroke. New-onset atrial fibrillation occurred more
      in the elderly, those with a prior history of cardiovascular and respiratory
      disease, and those with increased severity of illness. CONCLUSION: Prospective
      randomised trials are needed to clarify the significance of new-onset atrial
      fibrillation in sepsis, optimal treatment strategies for these patients, and the
      benefit of systemic anticoagulation. Physicians should be aware that new-onset
      atrial fibrillation in sepsis is not merely an observed temporary arrhythmia but
      a marker of poor prognosis and should be managed accordingly.

PMID- 25573849
TI  - What's to come after isolation of the pulmonary veins?

PMID- 25573850
TI  - Cardiac arrest during vigorous exercise: coronary plaque rupture or myocardial
      ischaemia?

PMID- 25573851
TI  - Ultrastructural maturation of human bone marrow mesenchymal stem cells-derived
      cardiomyocytes under alternative induction of 5-azacytidine.
AB  - Adult cardiomyocytes lack the ability to proliferate and are unable to repair
      damaged heart tissue, therefore differentiation of stem cells to cardiomyocytes
      represents an exceptional opportunity to study cardiomyocytes in vitro and
      potentially provides a valuable source for replacing damaged tissue. However,
      characteristic maturity of the in vitro differentiated cardiomyocytes and methods
      to achieve it are yet to be optimized. In this study, differentiation of human
      bone marrow-mesenchymal stem cells (hBM-MSCs) into cardiomyocytes is accomplished
      and the process investigated ultrastructurally. The hBM-MSCs were alternatively
      treated with 5 MUM of 5-azacytidine (5-aza) for 8 weeks resulting in
      differentiation to cardiomyocytes. Expressions of cardiomyocyte-specific genes
      [cardiac alpha-actinin, cardiac beta-myosin heavy chain (MHC) and connexin-43]
      and proteins (cardiac alpha-actinin, cardiac troponin and connexin-43) were
      confirmed in a time-dependent manner from the first to the fifth weeks post
      induction. Ultrastructural maturation of hBM-MSCs-derived cardiomyocyte (MSCs-CM)
      corresponded with increase in number and organization of myofilaments in cells
      over time. Starting from week five, organized myofibrils along with developing
      sarcomeres were detectable. Later on, MSCs-CM were characterized by the presence
      of sarcoplasmic reticulum, T-tubules and diads as cardiomyocytes connected to
      each other by intercalated disc-like structures. Here, we showed the potential of
      hBM-MSCs as a source for the production of cardiomyocytes and confirmed mature
      ultrastructural characteristics of these cells using our alternative incubation
      method. 

PMID- 25573852
TI  - Complement-mediated macrophage polarization in perivascular adipose tissue
      contributes to vascular injury in deoxycorticosterone acetate-salt mice.
AB  - OBJECTIVE: We have previously shown an increased expression of complement 3 (C3)
      in the perivascular adipose tissue (PVAT) in the deoxycorticosterone acetate
      (DOCA)-salt hypertensive model. This study aims to examine the role and
      underlying mechanism of C3 in PVAT for understanding the pathogenesis of
      hypertensive vascular remodeling further. APPROACH AND RESULTS: The role of C3 in
      macrophage polarization was investigated using peritoneal macrophages from wild
      type and C3-deficient (C3KO) mice because we found that C3 was primarily
      expressed in macrophages in PVAT of blood vessels from DOCA-salt mice, and
      results showed a decreased expression of M1 phenotypic marker in contrast to an
      increased level of M2 marker in the C3KO macrophages. Bone marrow transplantation
      studies further showed in vivo that DOCA-salt recipient mice had fewer M1 but
      more M2 macrophages in PVAT when the donor bone marrows were from C3KO compared
      with those from wild-type mice. Of note, this macrophage polarization shift was
      accompanied with an ameliorated vascular injury. Furthermore, we identified the
      complement 5a (C5a) as the major C3 activation product that was involved in
      macrophage polarization and DOCA-salt-induced vascular injury. Consistently, in
      vivo depletion of macrophages prevented the induction of C3 and C5a in PVAT, and
      ameliorated hypertensive vascular injury as well. CONCLUSIONS: The presence and
      activation of bone marrow-derived macrophages in PVAT are crucial for complement
      activation in hypertensive vascular inflammation, and C5a plays a critical role
      in DOCA-salt-induced vascular injury by stimulating macrophage polarization
      toward a proinflammatory M1 phenotype in PVAT.

PMID- 25573854
TI  - Triglyceride-rich lipoproteins and coronary artery disease risk: new insights
      from human genetics.

PMID- 25573853
TI  - Cholesterol loading reprograms the microRNA-143/145-myocardin axis to convert
      aortic smooth muscle cells to a dysfunctional macrophage-like phenotype.
AB  - OBJECTIVE: We previously showed that cholesterol loading in vitro converts mouse
      aortic vascular smooth muscle cells (VSMC) from a contractile state to one
      resembling macrophages. In human and mouse atherosclerotic plaques, it has become
      appreciated that ~40% of cells classified as macrophages by histological markers
      may be of VSMC origin. Therefore, we sought to gain insight into the molecular
      regulation of this clinically relevant process. APPROACH AND RESULTS: VSMC of
      mouse (or human) origin were incubated with cyclodextrin-cholesterol complexes
      for 72 hours, at which time the expression at the protein and mRNA levels of
      contractile-related proteins was reduced and of macrophage markers increased.
      Concurrent was downregulation of miR-143/145, which positively regulate the
      master VSMC differentiation transcription factor myocardin. Mechanisms were
      further probed in mouse VSMC. Maintaining the expression of myocardin or miR
      143/145 prevented and reversed phenotypic changes caused by cholesterol loading.
      Reversal was also seen when cholesterol efflux was stimulated after loading.
      Notably, despite expression of macrophage markers, bioinformatic analyses showed
      that cholesterol-loaded cells remained closer to the VSMC state, consistent with
      impairment in classical macrophage functions of phagocytosis and efferocytosis.
      In apoE-deficient atherosclerotic plaques, cells positive for VSMC and macrophage
      markers were found lining the cholesterol-rich necrotic core. CONCLUSIONS:
      Cholesterol loading of VSMC converts them to a macrophage-appearing state by
      downregulating the miR-143/145-myocardin axis. Although these cells would be
      classified by immunohistochemistry as macrophages in human and mouse plaques,
      their transcriptome and functional properties imply that their contributions to
      atherogenesis would not be those of classical macrophages.

PMID- 25573857
TI  - Child Behavior Questionnaire-Short Form for Teachers: Informant Correspondences
      and Divergences.
AB  - Discrepancies among independent sources of information about presumably identical
      constructs argue against reliance on a single perspective. To fill the need for
      temperament questionnaires for teacher and parent informants, we adapted the
      popular parent/caregiver Child Behavior Questionnaire-Short Form for preschool
      and kindergarten teachers. Informant correspondences were low as expected, but
      patterns were consistent with hypotheses drawn from person perception models.
      Internal consistencies of the teacher scales were adequate, comparing favorably
      with those of parent-rated scales. Anticipated relations of temperament scales
      emerged with social competence and tasks of executive attention for both parent
      and teacher informants. Confirmatory factor analyses conducted separately for
      parent and teacher scales supported the familiar three-factor model when
      allowances were made for cross-loadings and correlated errors. A multigroup
      confirmatory factor analyses with parent and teacher data indicated that the
      factor structures of the two questionnaires are similar but not equivalent. 

PMID- 25573858
TI  - Efficient high light acclimation involves rapid processes at multiple mechanistic
      levels.
AB  - Like no other chemical or physical parameter, the natural light environment of
      plants changes with high speed and jumps of enormous intensity. To cope with this
      variability, photosynthetic organisms have evolved sensing and response
      mechanisms that allow efficient acclimation. Most signals originate from the
      chloroplast itself. In addition to very fast photochemical regulation, intensive
      molecular communication is realized within the photosynthesizing cell, optimizing
      the acclimation process. Current research has opened up new perspectives on
      plausible but mostly unexpected complexity in signalling events, crosstalk, and
      process adjustments. Within seconds and minutes, redox states, levels of reactive
      oxygen species, metabolites, and hormones change and transmit information to the
      cytosol, modifying metabolic activity, gene expression, translation activity, and
      alternative splicing events. Signalling pathways on an intermediate time scale of
      several minutes to a few hours pave the way for long-term acclimation. Thereby, a
      new steady state of the transcriptome, proteome, and metabolism is realized
      within rather short time periods irrespective of the previous acclimation history
      to shade or sun conditions. This review provides a time line of events during six
      hours in the 'stressful' life of a plant. 

PMID- 25573859
TI  - Fruit growth-related genes in tomato.
AB  - Tomato (Solanum lycopersicum Mill.) represents a model species for all fleshy
      fruits due to its biological cycle and the availability of numerous genetic and
      molecular resources. Its importance in human nutrition has made it one of the
      most valuable worldwide commodities. Tomato fruit size results from the
      combination of cell number and cell size, which are determined by both cell
      division and expansion. As fruit growth is mainly driven by cell expansion, cells
      from the (fleshy) pericarp tissue become highly polyploid according to the
      endoreduplication process, reaching a DNA content rarely encountered in other
      plant species (between 2C and 512C). Both cell division and cell expansion are
      under the control of complex interactions between hormone signalling and carbon
      partitioning, which establish crucial determinants of the quality of ripe fruit,
      such as the final size, weight, and shape, and organoleptic and nutritional
      traits. This review describes the genes known to contribute to fruit growth in
      tomato. 

PMID- 25573860
TI  - EMA recommends restrictions on off-label use of antibiotics.

PMID- 25573856
TI  - Epigenetic profile of human adventitial progenitor cells correlates with
      therapeutic outcomes in a mouse model of limb ischemia.
AB  - OBJECTIVE: We investigated the association between the functional, epigenetic,
      and expressional profile of human adventitial progenitor cells (APCs) and
      therapeutic activity in a model of limb ischemia. APPROACH AND RESULTS: Antigenic
      and functional features were analyzed throughout passaging in 15 saphenous vein
      (SV)-derived APC lines, of which 10 from SV leftovers of coronary artery bypass
      graft surgery and 5 from varicose SV removal. Moreover, 5 SV-APC lines were
      transplanted (8*10(5) cells, IM) in mice with limb ischemia. Blood flow and
      capillary and arteriole density were correlated with functional characteristics
      and DNA methylation/expressional markers of transplanted cells. We report
      successful expansion of tested lines, which reached the therapeutic target of 30
      to 50 million cells in ~10 weeks. Typical antigenic profile, viability, and
      migratory and proangiogenic activities were conserved through passaging, with low
      levels of replicative senescence. In vivo, SV-APC transplantation improved blood
      flow recovery and revascularization of ischemic limbs. Whole genome screening
      showed an association between DNA methylation at the promoter or gene body level
      and microvascular density and to a lesser extent with blood flow recovery.
      Expressional studies highlighted the implication of an angiogenic network
      centered on the vascular endothelial growth factor receptor as a predictor of
      microvascular outcomes. FLT-1 gene silencing in SV-APCs remarkably reduced their
      ability to form tubes in vitro and support tube formation by human umbilical vein
      endothelial cells, thus confirming the importance of this signaling in SV-APC
      angiogenic function. CONCLUSIONS: DNA methylation landscape illustrates different
      therapeutic activities of human APCs. Epigenetic screening may help identify
      determinants of therapeutic vasculogenesis in ischemic disease.

PMID- 25573855
TI  - Cigarette smoking and cardiovascular events: role of inflammation and subclinical
      atherosclerosis from the MultiEthnic Study of Atherosclerosis.
AB  - OBJECTIVES: To examine the contemporary effect of smoking in a multiethnic
      sample, and to explore the respective contributions of inflammation and
      subclinical atherosclerosis to the cardiovascular consequences of smoking.
      APPROACH AND RESULTS: We studied 6814 participants free of cardiovascular disease
      and coronary heart disease (CHD) from the Multiethnic Study of Atherosclerosis.
      Smoking status and cumulative exposure were determined by self-report and
      confirmed by urinary cotinine. Multivariable Cox regression was used to estimate
      the association between smoking parameters and all-cause cardiovascular disease,
      all-cause CHD, and hard CHD events. We further adjusted for high-sensitivity C
      reactive protein and coronary artery calcium (CAC) in hierarchical Cox models. We
      identified 3218 never smokers, 2607 former smokers, and 971 current smokers.
      Median follow-up was 10.2 years. Compared with never smokers, adjusted hazard
      ratios in current smokers were 1.7 (95% confidence interval, 1.3-2.2) for all
      cause cardiovascular disease, 1.6 (1.1-2.1) for all-cause CHD, and 1.7 (1.2-2.4)
      for hard CHD. Similarly, among current smokers, hazard ratios were higher in the
      4th versus 1st quartile of pack-years (eg, all-cause CHD hazard ratio=2.7 [1.1
      6.6]). Both CAC>100 and high-sensitivity C-reactive protein >=3 mg/L identified
      higher relative risk among current smokers (eg, all-cause CHD hazard ratio of 3.0
      [1.5-6.0, compared with CAC=0] and 2.6 [1.4-4.8, compared with high-sensitivity C
      reactive protein <2 mg/L], respectively). However, CAC was a stronger mediator of
      events and adversely modified the effect of smoking on events (eg, P
      interaction=0.02 for hard CHD). Compared with never smokers, former smokers
      (median cessation interval=22 years) had similar adjusted hazard for events.
      CONCLUSIONS: In this multiethnic cohort, current smoking and cumulative exposure
      remain important modifiable determinants of cardiovascular disease. Both high
      sensitivity C-reactive protein >=3 mg/L and, particularly, CAC>100 identified
      high-risk smokers who may benefit from more intensive smoking-cessation efforts.

PMID- 25573862
TI  - Simple meat labelling would be a step in the right direction, says BVA.

PMID- 25573861
TI  - More than 1300 badgers vaccinated against bovine TB in Wales last year.

PMID- 25573863
TI  - Dr yes or Dr no?

PMID- 25573865
TI  - Schools benefit from new microscopes.

PMID- 25573864
TI  - Diclofenac residues pose risk to European vultures, advises EMA.

PMID- 25573867
TI  - Challenges associated with parasite control in travelling pets.

PMID- 25573866
TI  - Thinking differently about surveillance.

PMID- 25573868
TI  - Developing best practice guidelines on equine colic.

PMID- 25573869
TI  - UK charity supports centre producing vaccine against East Coast fever.

PMID- 25573870
TI  - Veterinary medicines: product update.

PMID- 25573871
TI  - Elanco completes acquisition of Novartis.

PMID- 25573872
TI  - Progressive Charolais ataxia in calves.

PMID- 25573873
TI  - Power of practice: using clinical data to advance veterinary medicine.

PMID- 25573874
TI  - Official veterinarians in Scotland.

PMID- 25573876
TI  - Conserving wildlife.

PMID- 25573875
TI  - Results of the 2014 badger cull.

PMID- 25573877
TI  - First-year student diary.

PMID- 25573878
TI  - Decrease in circulating concentrations of soluble receptors for advanced
      glycation end products at the time of seroconversion to autoantibody positivity
      in children with prediabetes.
AB  - OBJECTIVE: Dietary advanced glycation end products (AGEs) and their interactions
      with the receptor for AGEs (RAGE) may play a role in the pathogenesis of type 1
      diabetes. This study set out to assess whether there is any association of
      circulating concentrations of soluble RAGE (sRAGE), AGEs, and their ratio with
      the appearance of diabetes-associated autoantibodies in children progressing to
      clinical diabetes. RESEARCH DESIGN AND METHODS: Serum concentrations of sRAGE, N
      epsilon(carboxymethyl)lysine (CML) adducts, and the sRAGE/CML ratio were analyzed
      in children who progressed to type 1 diabetes. The samples were taken at four
      time points: before seroconversion, at the time of the first autoantibody
      positive sample, at the time of the first sample positive for multiple (>2)
      autoantibodies, and close to the disease diagnosis. Samples of autoantibody
      negative controls matched for age, sex, and HLA-conferred diabetes risk were
      analyzed at corresponding time points. RESULTS: The prediabetic children had
      higher sRAGE concentrations before seroconversion (Pc = 0.03), at the appearance
      of multiple autoantibodies (Pc = 0.008), and close to diagnosis (Pc = 0.04).
      Close to diagnosis, the cases had lower CML concentrations than the controls (Pc
      = 0.004). Prediabetic children had a higher sRAGE/CML ratio than the controls
      before seroconversion (Pc = 0.008) and at diagnosis (Pc < 0.001). CONCLUSIONS:
      Prediabetic children have higher concentrations of sRAGE and a higher sRAGE/CML
      ratio than healthy controls. Circulating sRAGE concentrations seem to decline
      with the appearance of diabetes-predictive autoantibodies in children progressing
      to type 1 diabetes. The higher sRAGE/CML ratio in prediabetic children may
      reflect a higher AGE scavenger capacity.

PMID- 25573879
TI  - Insulin cessation and diabetes remission after bariatric surgery in adults with
      insulin-treated type 2 diabetes.
AB  - OBJECTIVE: The impact of bariatric surgeries on insulin-treated type 2 diabetes
      (I-T2D) in the general population is largely undocumented. We assessed changes in
      insulin treatment after bariatric surgery in a large cohort of I-T2D patients,
      comparing Roux-en-Y gastric bypass surgery (RYGB) with laparoscopic adjustable
      gastric banding (LAGB), controlling for differences in weight loss between
      procedures. RESEARCH DESIGN AND METHODS: Of 113,638 adult surgical patients in
      the Bariatric Outcomes Longitudinal Database (BOLD), 10% had I-T2D. Analysis was
      restricted to 5,225 patients with I-T2D and at least 1 year of postoperative
      follow-up. Regression models were used to identify factors that predict cessation
      of insulin therapy. To control for differences in weight loss patterns between
      RYGB and LAGB, a case-matched analysis was also performed. RESULTS: Of I-T2D
      patients who underwent RYGB (n = 3,318), 62% were off insulin at 12 months
      compared with 34% (n = 1,907) after LAGB (P < 0.001). Regression analysis
      indicated that RYGB strongly predicted insulin cessation at both 1 and 12 months
      postoperatively. In the case-matched analysis at 3 months, the proportion of
      insulin cessation was significantly higher in the RYGB group than in the LAGB
      group (P = 0.03), and the diabetes remission rate was higher at all time points
      after this surgery. RYGB was a weight-independent predictor of insulin therapy
      cessation early after surgery, whereas insulin cessation after LAGB was linked to
      weight loss. CONCLUSIONS: I-T2D patients have a greater probability of stopping
      insulin after RYGB than after LAGB (62% vs. 34%, respectively, at 1 year), with
      weight-independent effects in the early months after surgery. These findings
      support RYGB as the procedure of choice for reversing I-T2D.

PMID- 25573881
TI  - Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in
      type 1 diabetes.
AB  - OBJECTIVE: This study determined if deficits in corneal nerve fiber length (CNFL)
      assessed using corneal confocal microscopy (CCM) can predict future onset of
      diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: CNFL and a
      range of other baseline measures were compared between 90 nonneuropathic patients
      with type 1 diabetes who did or did not develop DPN after 4 years. The receiver
      operator characteristic (ROC) curve was used to determine the capability of
      single and combined measures of neuropathy to predict DPN. RESULTS: DPN developed
      in 16 participants (18%) after 4 years. Factors predictive of 4-year incident DPN
      were lower CNFL (P = 0.041); longer duration of diabetes (P = 0.002); higher
      triglycerides (P = 0.023); retinopathy (higher on the Early Treatment of Diabetic
      Retinopathy Study scale) (P = 0.008); nephropathy (higher albumin-to-creatinine
      ratio) (P = 0.001); higher neuropathy disability score (P = 0.037); lower cold
      sensation (P = 0.001) and cold pain (P = 0.027) thresholds; higher warm sensation
      (P = 0.008), warm pain (P = 0.024), and vibration (P = 0.003) thresholds;
      impaired monofilament response (P = 0.003); and slower peroneal (P = 0.013) and
      sural (P = 0.002) nerve conduction velocity. CCM could predict the 4-year
      incident DPN with 63% sensitivity and 74% specificity for a CNFL threshold cutoff
      of 14.1 mm/mm(2) (area under ROC curve = 0.66, P = 0.041). Combining neuropathy
      measures did not improve predictive capability. CONCLUSIONS: DPN can be predicted
      by various demographic, metabolic, and conventional neuropathy measures. The
      ability of CCM to predict DPN broadens the already impressive diagnostic
      capabilities of this novel ophthalmic marker.

PMID- 25573880
TI  - Risk and recurrence of serious adverse outcomes in the first and second
      pregnancies of women with preexisting diabetes.
AB  - OBJECTIVE: Women with preexisting (type 1 or type 2) diabetes experience an
      increased risk of serious adverse pregnancy outcomes. It is not known, however,
      how these risks change between the first and second pregnancy and whether there
      is an increased risk of recurrence. This study describes the absolute risks and
      recurrence of serious adverse pregnancy outcomes in 220 women with preexisting
      diabetes. RESEARCH DESIGN AND METHODS: A total of 440 pregnancies occurring in
      220 women with preexisting diabetes who delivered successive singleton
      pregnancies in the North of England during 1996-2008 were identified from the
      Northern Diabetes in Pregnancy Survey (NorDIP). Predictors of serious adverse
      outcome were estimated by competing-risks regression. RESULTS: Sixty-seven first
      pregnancies (30.5%) ended in serious adverse outcome, including 14 (6.4%) with
      congenital anomalies and 53 (24.1%) additional fetal or infant deaths. Thirty
      seven second pregnancies (16.8%) ended in serious adverse outcome--half the rate
      among first pregnancies (P = 0.0004)--including 21 (9.5%) with congenital
      anomalies and 16 (7.3%) additional fetal or infant deaths. Serious adverse
      outcomes in the second pregnancy occurred twice as frequently in women who
      experienced a previous adverse outcome than in those who did not (26.9% vs.
      12.4%, P = 0.004), but previous adverse outcome was not associated with
      preparation for the following pregnancy. CONCLUSIONS: Serious adverse outcomes
      are less common in the second pregnancies of women with preexisting diabetes,
      although the risk is comparable in those whose first pregnancy ends in adverse
      outcome. Reducing the risk of recurrence may require more support in the
      immediate period after an adverse pregnancy outcome.

PMID- 25573882
TI  - Cardiac autonomic dysfunction is associated with high-risk albumin-to-creatinine
      ratio in young adolescents with type 1 diabetes in AdDIT (adolescent type 1
      diabetes cardio-renal interventional trial).
AB  - OBJECTIVE: This study examined the association between cardiac autonomic
      dysfunction and high albumin-to-creatinine ratio (ACR) in adolescents with type 1
      diabetes. RESEARCH DESIGN AND METHODS: Adolescents recruited as part of a
      multicenter screening study (n = 445, 49% female, aged 10-17 years, mean duration
      6.9 years; mean HbA1c 8.4%, 68 mmol/mol) underwent a 10-min continuous
      electrocardiogram recording for heart rate variability analysis. Time-domain
      heart rate variability measures included baseline heart rate, SD of the R-R
      interval (SDNN), and root mean squared difference of successive R-R intervals
      (RMSSD). Spectral analysis included sympathetic (low-frequency) and
      parasympathetic (high-frequency) components. Standardized ACR were calculated
      from six early morning urine collections using an established algorithm,
      reflecting age, sex, and duration, and stratified into ACR tertiles, where the
      upper tertile reflects higher nephropathy risk. RESULTS: The upper-tertile ACR
      group had a faster heart rate (76 vs. 73 bpm; P < 0.01) and less heart rate
      variability (SDNN 68 vs. 76 ms, P = 0.02; RMSSD 63 vs. 71 ms, P = 0.04). HbA1c
      was 8.5% (69 mmol/mmol) in the upper tertile vs. 8.3% (67 mmol/mol) in the lower
      tertiles (P = 0.07). In multivariable analysis, upper-tertile ACR was associated
      with faster heart rate (beta = 2.5, 95% CI 0.2-4.8, P = 0.03) and lower RMSSD
      (beta = -9.5, 95% CI -18.2 to -0.8, P = 0.03), independent of age and HbA1c.
      CONCLUSIONS: Adolescents at potentially higher risk for nephropathy show an
      adverse cardiac autonomic profile, indicating sympathetic overdrive, compared
      with the lower-risk group. Longitudinal follow-up of this cohort will further
      characterize the relationship between autonomic and renal dysfunction and the
      effect of interventions in this population.

PMID- 25573884
TI  - Glycemic variability is associated with reduced cardiac autonomic modulation in
      women with type 2 diabetes.
AB  - OBJECTIVE: To investigate the sex differences in cardiac autonomic modulation in
      patients with newly diagnosed type 2 diabetes and to determine whether cardiac
      autonomic modulation is associated with glycemic variability. RESEARCH DESIGN AND
      METHODS: We investigated a cohort consisting of 48 men and 39 women with non
      insulin-treated type 2 diabetes and a known duration of diabetes <5 years. All
      patients were equipped with a continuous glucose monitoring sensor for 3 days,
      and the mean amplitude of glycemic excursions (MAGE) was calculated to obtain
      individual glycemic variability. Cardiac autonomic modulation was quantified by
      analysis of heart rate variability (HRV) in time and frequency domains and during
      cardiovascular reflex tests (response to standing [RS], deep breathing
      [expiration-inspiration], and Valsalva maneuver). RESULTS: Sex differences in age
      and heart rate-adjusted HRV measures were observed in both active and passive
      tests. Low frequency (LF; P = 0.036), LF/high frequency (HF; P < 0.001), and RS
      (P = 0.006) were higher in men, whereas expiration-inspiration (P < 0.001), but
      not HF, was higher in women. In women, reduced cardiac autonomic modulation as
      assessed by the standard deviation of normal-to-normal intervals (P = 0.001), the
      root mean square of successive differences (P = 0.018), LF (P < 0.001), HF (P =
      0.005), total power (P = 0.008), RS ratio (P = 0.027), and expiration-to
      inspiration ratio (P = 0.006) was significantly associated with increased
      glycemic variability as assessed by MAGE. This was not the case in men. The
      association in women persisted in a multivariate regression analysis controlling
      for weight, mean heart rate, blood pressure (systolic), and triglycerides.
      CONCLUSIONS: In patients with newly diagnosed and well-controlled type 2
      diabetes, increased glycemic variability was associated with reduced cardiac
      autonomic modulation in women but not in men.

PMID- 25573883
TI  - Determinants of adherence to diabetes medications: findings from a large pharmacy
      claims database.
AB  - OBJECTIVE: Adults with diabetes typically take multiple medications for
      hyperglycemia, diabetes-associated conditions, and other comorbidities.
      Medication adherence is associated with improved outcomes, including reduced
      health care costs, hospitalization, and mortality. We conducted a retrospective
      analysis of a large pharmacy claims database to examine patient, medication, and
      prescriber factors associated with adherence to antidiabetic medications.
      RESEARCH DESIGN AND METHODS: We extracted data on a cohort of >200,000 patients
      who were treated for diabetes with noninsulin medications in the second half of
      2010 and had continuous prescription benefits eligibility through 2011. Adherence
      was defined as a medication possession ratio >= 0.8. We used a modified adherence
      measure that accounted for switching therapies. Logistic regression analysis was
      performed to determine factors independently associated with adherence. RESULTS:
      Sixty-nine percent of patients were adherent. Adherence was independently
      associated with older age, male sex, higher education, higher income, use of mail
      order versus retail pharmacies, primary care versus nonendocrinology specialist
      prescribers, higher daily total pill burden, and lower out-of-pocket costs.
      Patients who were new to diabetes therapy were significantly less likely to be
      adherent. CONCLUSIONS: Several demographic, clinical, and potentially modifiable
      system-level factors were associated with adherence to antidiabetic medications.
      Patients typically perceived to be healthy (those who are younger, new to
      diabetes, and on few other medications) may be at risk for nonadherence. For all
      patients, efforts to reduce out-of-pocket costs and encourage use of mail order
      pharmacies may result in higher adherence.

PMID- 25573886
TI  - Functional characterization of hesp018, a baculovirus-encoded serpin gene.
AB  - The serpin family of serine proteinase inhibitors plays key roles in a variety of
      biochemical pathways. In insects, one of the important functions carried out by
      serpins is regulation of the phenoloxidase (PO) cascade - a pathway that produces
      melanin and other compounds that are important in insect humoral immunity. Recent
      sequencing of the baculovirus Hemileuca sp. nucleopolyhedrovirus (HespNPV) genome
      revealed the presence of a gene, hesp018, with homology to insect serpins. To our
      knowledge, hesp018 is the first viral serpin homologue to be characterized
      outside of the chordopoxviruses. The Hesp018 protein was found to be a functional
      serpin with inhibitory activity against a subset of serine proteinases. Hesp018
      also inhibited PO activation when mixed with lepidopteran haemolymph. The Hesp018
      protein was secreted when expressed in lepidopteran cells and a baculovirus
      expressing Hesp018 exhibited accelerated production of viral progeny during in
      vitro infection. Expression of Hesp018 also reduced caspase activity induced by
      baculovirus infection, but caused increased cathepsin activity. In infected
      insect larvae, expression of Hesp018 resulted in faster larval melanization,
      consistent with increased activity of viral cathepsin. Finally, expression of
      Hesp018 increased the virulence of a prototype baculovirus by fourfold in orally
      infected neonate Trichoplusia ni larvae. Based on our observations, we
      hypothesize that hesp018 may have been retained in HespNPV due to its ability to
      inhibit the activity of select host proteinases, possibly including proteinases
      involved in the PO response, during infection of host insects.

PMID- 25573885
TI  - n-3 Fatty acids attenuate the risk of diabetes associated with elevated serum
      nonesterified fatty acids: the multi-ethnic study of atherosclerosis.
AB  - OBJECTIVE: Chronically high nonesterified fatty acids (NEFAs) are a marker of
      metabolic dysfunction and likely increase risk of type 2 diabetes. By comparison,
      n-3 fatty acids (FAs) have been shown to have various health benefits and may
      protect against disease development. In 5,697 participants of the Multi-Ethnic
      Study of Atherosclerosis (MESA), we examined whether serum levels of NEFAs relate
      to risk of incident type 2 diabetes and further tested whether plasma n-3 FA
      levels may interact with this relation. RESEARCH DESIGN AND METHODS: NEFAs were
      measured in fasting serum using an enzymatic colorimetric assay and phospholipid
      n-3 FAs eicosapentaenoic and docosahexaenoic acids were determined in plasma
      through gas chromatography-flame ionization detection in 5,697 MESA participants.
      Cox proportional hazards regression evaluated the association between NEFA levels
      and incident type 2 diabetes and whether plasma n-3 FAs modified this association
      adjusting for age, sex, race, education, field center, smoking, and alcohol use.
      RESULTS: Over a mean 11.4 years of the study period, higher diabetes incidence
      was found across successive NEFA quartiles (Q) (hazard ratio [95% CI]): Q1, 1.0;
      Q2, 1.35 (1.07, 1.71); Q3, 1.58 (1.24, 2.00); and Q4, 1.86 (1.45, 2.38) (P(trend)
      < 0.001). A significant interaction of n-3 FAs on the relation between NEFAs and
      type 2 diabetes was also observed (P(interaction) = 0.03). For individuals with
      lower n-3 levels (<75th percentile), a higher risk of type 2 diabetes was
      observed across quartiles of NEFAs: Q1, 1.0; Q2, 1.41 (1.07, 1.84); Q3, 1.77
      (1.35, 2.31); and Q4, 2.18 (1.65, 2.88) (P(trend) < 0.001). No significant
      associations were observed in those with n-3 FAs >= 75th percentile (P(trend) =
      0.54). CONCLUSIONS: NEFAs are a marker of type 2 diabetes and may have clinical
      utility for detecting risk of its development. The modifying influence of n-3 FAs
      suggests a protective effect against disease and/or metabolic dysfunction related
      to NEFAs and requires further study.

PMID- 25573887
TI  - Loperamide therapy for voluminous diarrhea in Ebola virus disease.

PMID- 25573888
TI  - [A therapeutic pathway for the hospital treatment of schizophrenia --
      recommendations based on the consensus of the Hungarian expert committee].

PMID- 25573890
TI  - Sporothrix and sporotrichosis: contributions from the first international meeting
      sponsored by the Working Group on Sporothrix and sporotrichosis of the
      International Society for Human and Animal Mycology, Rio de Janeiro, Brazil,
      October, 2013.

PMID- 25573889
TI  - Plasma cholesterol efflux capacity from human THP-1 macrophages is reduced in HIV
      infected patients: impact of HAART.
AB  - The capacity of HDL to remove cholesterol from macrophages is inversely
      associated with the severity of angiographic coronary artery disease. The effect
      of human immunodeficiency virus (HIV) infection or its treatment on the ability
      of HDL particles to stimulate cholesterol efflux from human macrophages has never
      been studied. We evaluated the capacity of whole plasma and isolated HDL
      particles from HIV-infected subjects (n = 231) and uninfected controls (n = 200),
      as well as in a subset of 41 HIV subjects receiving highly active antiretroviral
      therapy (HAART) to mediate cholesterol efflux from human macrophages. Plasma
      cholesterol efflux capacity was reduced (-12%; P = 0.001) in HIV patients as
      compared with controls. HIV infection reduced by 27% (P < 0.05) the capacity of
      HDL subfractions to promote cholesterol efflux from macrophages. We observed a
      reduced ABCA1-dependent efflux capacity of plasma (-27%; P < 0.0001) from HIV
      infected subjects as a result of a reduction in the efflux capacity of HDL3
      particles. HAART administration restored the capacity of plasma from HIV patients
      to stimulate cholesterol efflux from human macrophages (9.4%; P = 0.04). During
      HIV infection, the capacity of whole plasma to remove cholesterol from
      macrophages is reduced, thus potentially contributing to the increased coronary
      heart disease in the HIV population. HAART administration restored the removal of
      cholesterol from macrophages by increasing HDL functionality. 

PMID- 25573894
TI  - A meta-analysis of biomarkers related to oxidative stress and nitric oxide
      pathway in migraine.
AB  - BACKGROUND: Oxidative and nitrosative stress are considered key events in the
      still unclear pathophysiology of migraine. METHODS: Studies comparing the level
      of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the
      blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed
      database. Summary estimates of mean ratios (MR) were carried out whenever a
      minimum of three papers were available. Nineteen studies were included in the
      meta-analyses, accounting for more than 1000 patients and controls, and compared
      with existing literature. RESULTS: Most studies measuring superoxide dismutase
      (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes
      gave null results. On the contrary, plasma levels of thiobarbituric acid reactive
      substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR
      of 2.20 (95% CI: 1.65-2.93). As for NOs, no significant results were found in
      plasma, serum and urine. However, higher levels were shown during attacks, in
      patients with aura, and an effect of diet was found. The analysis of glutathione
      precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase
      inhibitor, gave inconclusive results. CONCLUSIONS: The role of the oxidative
      pathway in migraine is still uncertain. Interesting evidence emerged for TBARS
      and SOD, and concerning the possible role of diet in the control of NOx levels.

PMID- 25573893
TI  - Sleep and chronobiology in cluster headache.
AB  - BACKGROUND AND AIM: Cluster headache (CH) is the headache disorder with the
      strongest chronobiological traits. The severe attacks of pain occur with diurnal
      and annual rhythmicity but the precise rhythm and involvement of potential
      zeitgebers is unknown. Patients complain of poor sleep quality yet this has never
      been studied. We investigated triggers, rhythms, sleep quality and chronotypes in
      CH. METHODS: Patients and controls completed questionnaires and structured
      interviews composed of new and previously validated parts including the
      Pittsburgh Sleep Quality Index (PSQI) and Morningness-Eveningness Questionnaire
      (MEQ). Patients were characterized by a CH index, a unified measure of headache
      burden. RESULTS: A total of 275 CH patients and 145 matched controls were
      included. The most common trigger was sleep (80%) and a relationship between
      clusters and daylight was identified. Of the patients, 82.2% reported diurnal and
      56% annual rhythmicity. Patients reported impaired sleep quality (PSQI) (p <
      0.0001) and an inverse relationship between time passed since last attack and
      sleep quality was identified (p < 0.0001). The CH index was positively related to
      the PSQI (p < 0.0001). CONCLUSION: Diurnally, CH exhibits a relationship with
      night-time and annually with daylight hours. Patients' sleep quality is reduced
      compared with controls. Results suggest a complex relationship as sleep quality
      improves between clusters, but remains pathological.

PMID- 25573895
TI  - Can nitric oxide induce migraine in normal individuals?
AB  - INTRODUCTION: For many years, scientists have debated the possibility that an
      individual "migraine threshold" determines the likelihood with which individuals
      may express migraine attacks. DISCUSSION: Recent discoveries provided evidence
      for both genetic and environmental influences on individual migraine expression.
      The question is whether any person may express a migraine attack given a
      sufficiently strong stimulus or provocation. Here, we reviewed and discussed the
      ability of nitric oxide to induce migraine-like attacks in normal individuals.
      CONCLUSION: Experimental data show that normal individuals may develop a migraine
      like attack and that the human data point to different ways of further developing
      existing animal and human models.

PMID- 25573896
TI  - Reversible cerebral vasoconstriction mimicking posterior reversible
      encephalopathy syndrome in an infant with end-stage renal disease.

PMID- 25573892
TI  - The CXCR3-CXCL11 signaling axis mediates macrophage recruitment and dissemination
      of mycobacterial infection.
AB  - The recruitment of leukocytes to infectious foci depends strongly on the local
      release of chemoattractant mediators. The human CXC chemokine receptor 3 (CXCR3)
      is an important node in the chemokine signaling network and is expressed by
      multiple leukocyte lineages, including T cells and macrophages. The ligands of
      this receptor originate from an ancestral CXCL11 gene in early vertebrates. Here,
      we used the optically accessible zebrafish embryo model to explore the function
      of the CXCR3-CXCL11 axis in macrophage recruitment and show that disruption of
      this axis increases the resistance to mycobacterial infection. In a mutant of the
      zebrafish ortholog of CXCR3 (cxcr3.2), macrophage chemotaxis to bacterial
      infections was attenuated, although migration to infection-independent stimuli
      was unaffected. Additionally, attenuation of macrophage recruitment to infection
      could be mimicked by treatment with NBI74330, a high-affinity antagonist of
      CXCR3. We identified two infection-inducible CXCL11-like chemokines as the
      functional ligands of Cxcr3.2, showing that the recombinant proteins exerted a
      Cxcr3.2-dependent chemoattraction when locally administrated in vivo. During
      infection of zebrafish embryos with Mycobacterium marinum, a well-established
      model for tuberculosis, we found that Cxcr3.2 deficiency limited the macrophage
      mediated dissemination of mycobacteria. Furthermore, the loss of Cxcr3.2 function
      attenuated the formation of granulomatous lesions, the typical histopathological
      features of tuberculosis, and led to a reduction in the total bacterial burden.
      Prevention of mycobacterial dissemination by targeting the CXCR3 pathway,
      therefore, might represent a host-directed therapeutic strategy for treatment of
      tuberculosis. The demonstration of a conserved CXCR3-CXCL11 signaling axis in
      zebrafish extends the translational applicability of this model for studying
      diseases involving the innate immune system. 

PMID- 25573897
TI  - Reducing migraine return with corticosteroids: An extra chance to improve
      migraine care.

PMID- 25573898
TI  - An unusual case of CSF leak following post-traumatic rupture of a sacral
      meningeal cyst.

PMID- 25573899
TI  - RBM20 is an essential factor for thyroid hormone-regulated titin isoform
      transition.

PMID- 25573900
TI  - Can we improve service efficiency in CAMHS using the CAPA approach without
      reducing treatment effectiveness?
AB  - Health-care systems are under increasing pressure to deliver more care with
      similar or even less resources and there is concern that this may be achieved at
      the cost of reduced clinical effectiveness. In Child and Adolescent Mental Health
      Services (CAMHS), the Choice and Partnership Approach (CAPA) has been widely
      adopted as a way of increasing the efficient use of limited service resources.
      Some evaluations have reported increased patient flow and reduced waiting times,
      but it remains unknown whether such changes have been achieved at a cost of
      clinical effectiveness. This article describes a pragmatic multi-method
      evaluation of a CAMHS service reporting service outcomes (client satisfaction,
      waiting times, and patient flow) and clinical outcomes (clinician-rated clinical
      outcomes and goals achieved by families). Results showed improved service
      outcomes (high levels of client satisfaction and reduced waiting times) and an
      increase in patient flow (49 cases increased to 72 cases over an equivalent time
      period). Clinical outcomes showed no reduction in effectiveness and a significant
      improvement against the agreed goals of the intervention. The evaluation
      suggested that a well-structured goal-focused patient flow system may improve
      services by increasing patient flow while maintaining high satisfaction levels,
      without negatively impacting clinical effectiveness.

PMID- 25573901
TI  - Self-reported need for psychotherapy predicts interferon-induced depression in
      hepatitis C: stratification for interferon-free treatment.
AB  - BACKGROUND: Interferon (IFN)-induced depression occurs in approximately 30% of
      chronic hepatitis C (CHC) patients undergoing pegylated (PEG)-IFN-based antiviral
      therapy. While IFN-free therapy has been developed, it is not accessible to all
      CHC patients due to the high costs of treatment. This study evaluated the
      Assessment of Demand for Additional Psychological Treatment (ADAPT) questionnaire
      as a screening tool for patients at risk of IFN-induced depression, in order to
      identify patients who may uniquely benefit from IFN-free regimens. METHODS: In
      this prospective study, consecutive patients being treated for CHC with PEG-IFN
      based antiviral therapy were examined for the occurrence of depression during a
      12-week treatment period. Using univariate and multivariate regression models,
      the value of the ADAPT questionnaire, in comparison to the Hospital Anxiety and
      Depression Scale (HADS), and the patients' psychiatric history was analysed.
      RESULTS: A total of 103 patients (59% male; median age 42) were included, of whom
      25% (26/103) developed IFN-induced depression during the study period. HADS
      Depression (D) subscale (OR=1.187, P=0.003; area under the curve [AUC]=0.690) and
      ADAPT-Psychotherapy (PT) subscale (OR=1.020, P=0.006; AUC=0.695) showed the
      highest accuracy for identification of patients at risk for depression. A HADS-D
      score of >=7 and an ADAPT-PT score of >=37.8 showed a similar sensitivity (61.5%
      versus 57.7%), whereas ADAPT-PT showed a more favourable specificity (68.9%
      versus 77.4%). CONCLUSIONS: The ADAPT-PT subscale effectively identifies patients
      at risk for IFN-induced depression and should therefore be taken into account
      when allocating patients to IFN-free antiviral treatment regimens.

PMID- 25573902
TI  - TMEFF2 is an endogenous inhibitor of the CRH signal transduction pathway.
AB  - TMEFF2 is a transmembrane protein with unknown function, containing an altered
      epidermal growth factor (EGF)-like motif, two follistatin-like domains, and a
      cytosolic tail with a putative G-protein-activating motif. TMEFF2 is
      predominantly expressed in brain and prostate and has been implicated in cell
      signaling, neuronal cell survival, and tumor suppression. We found that
      expression of TMEFF2 in pituitary corticotrope cells inhibits the effects of
      corticotropin-releasing hormone (CRH) on the production of intracellular cAMP,
      and CREB, and transcription of Pomc. Regulation of the activity of CRH by TMEFF2
      requires neither the cytoplasmic tail nor the EGF domain, while deletion of the
      follistatin modules abolishes the inhibitory function of TMEFF2. Moreover, a
      soluble secreted protein containing the complete extracellular domain is
      sufficient for inhibition of CRH signaling. TMEFF2-induced inhibition depends on
      serum components. Furthermore, TMEFF2 regulates the non-canonical activin/BMP4
      signaling, PI3K, and Ras/ERK1/2 pathways. Thus, TMEFF2 inhibits the CRH signaling
      pathway and the PI3K/AKT and Ras/ERK1/2 pathways, contributing to a significant
      inhibition of transcription of Pomc. We found that expression of TMEFF2 in human
      Cushing's adenoma is reduced when compared with normal human pituitary, which may
      indicate that TMEFF2 acts as a tumor suppressor in these adenomas. Furthermore,
      the overexpression of TMEFF2 decreased proliferation of corticotrope cells. Our
      results indicate a potential therapeutic use of TMEFF2 or factors that stimulate
      the activity of TMEFF2 for the treatment of corticotrope tumors in order to
      reduce their secretion of ACTH and proliferation. 

PMID- 25573903
TI  - The effect of acceptance of illness on the quality of life in patients with
      chronic heart failure.
AB  - BACKGROUND: Although important, a relationship between acceptance of illness and
      quality of life has not been studied extensively in individuals with chronic
      heart failure. AIMS: The aim of this study was to analyse an association between
      these two variables in a large group of individuals with at least a six-month
      history of heart failure. METHODS: The study included 100 patients (68 men and 32
      women, mean age 63.2+/-12.2 years) with at least six months' clinical evidence of
      heart failure corresponding to New York Heart Association class II, III or IV.
      All the patients were examined with the Nottingham Health Profile (NHP)
      questionnaire and Acceptance of Illness Scale (AIS). RESULTS: The patients
      presenting with low levels of acceptance of illness (8-18 points) scored
      significantly higher on the energy, pain, emotional reaction, sleep, social
      isolation and mobility domains of the NHP. Multivariate analysis showed that
      acceptance of illness was the only independent predictor of quality of life in
      all the NHP domains: energy (beta= -0.653, p<0.001), pain (beta= -1.464,
      p<0.001), emotional reactions (beta -1.738, p<0.001), sleep (beta= -0.820,
      p<0.001), social isolation (beta= -0.638, p<0.001) and mobility (beta= -1.739,
      p<0.001). Male gender proved to be an independent predictor of lower pain scores
      (beta= -1.320, p= 0.001) and divorce was associated with higher social isolation
      scores (beta=1.948, p<0.001). CONCLUSION: The extent a patient accepts their
      chronic heart failure diagnosis has been shown to impact on their quality of
      life.

PMID- 25573904
TI  - A novel ritonavir paediatric powder formulation is bioequivalent to ritonavir
      oral solution with a similar food effect.
AB  - BACKGROUND: A novel ritonavir oral powder formulation has been developed to
      eliminate the alcohol and propylene glycol contents in the current ritonavir oral
      solution for paediatric use. Two clinical studies were conducted to assess the
      bioequivalence of the powder formulation to the marketed oral solution and to
      evaluate the effect of food and vehicles on bioavailability. METHODS: Study 1 was
      a randomized, partial-crossover, 4-period study in 48 subjects. Regimens
      included: oral solution under moderate-fat conditions, powder formulation in
      water under fasting, moderate-fat or high-fat conditions, and powder formulation
      in chocolate milk or pudding under moderate-fat conditions. Study 2 was a
      randomized, crossover, 4-period study in 24 subjects. Subjects were randomized to
      a sequence of the oral solution and powder formulation in water, infant formula
      and apple sauce, all under moderate-fat conditions. Bioavailability comparisons
      were assessed by the 90% CIs for the geometric least-squares mean ratios.
      RESULTS: Ritonavir powder formulation in water was found to be bioequivalent to
      the marketed oral solution. Ritonavir powder formulation administered in
      chocolate milk, pudding, infant formula or apple sauce was bioequivalent to the
      powder formulation administered in water. Compared with fasting conditions,
      moderate-fat and high-fat meals were associated with approximately 25-40% and 35
      50% reduction in ritonavir concentrations, respectively. CONCLUSIONS: The novel
      ritonavir powder formulation is bioequivalent to marketed ritonavir oral solution
      under moderate-fat conditions with a similar effect of meals. None of the
      vehicles tested negatively affected the bioavailability, which suggests the
      potential for use of a broad range of vehicles for dose preparation.

PMID- 25573906
TI  - Persistence of subgenomes in paleopolyploid cotton after 60 my of evolution.
AB  - The importance of whole-genome multiplication (WGM) in plant evolution has long
      been recognized. In flowering plants, WGM is both ubiquitous and in many lineages
      cyclical, each round followed by substantial gene loss (fractionation). This
      process may be biased with respect to duplicated chromosomes, often with
      overexpression of genes in less fractionated relative to more fractionated
      regions. This bias is hypothesized to arise through downregulation of gene
      expression through silencing of local transposable elements (TEs). We assess
      differences in gene expression between duplicated regions of the paleopolyploid
      cotton genome and demonstrate that the rate of fractionation is negatively
      correlated with gene expression. We examine recent hypotheses regarding the
      source of fractionation bias and show that TE-mediated, positional downregulation
      is absent in the modern cotton genome, seemingly excluding this phenomenon as the
      primary driver of biased gene loss. Nevertheless, the paleo subgenomes of diploid
      cotton are still distinguishable with respect to TE content, targeting of 24-nt
      small interfering RNAs and GC content, despite approximately 60 My of evolution.
      We propose that repeat content per se and differential recombination rates may
      drive biased fractionation following WGM. These data highlight the likely
      importance of ancient genomic fractionation biases in shaping modern crop
      genomes. 

PMID- 25573905
TI  - Lateral gene transfer and gene duplication played a key role in the evolution of
      Mastigamoeba balamuthi hydrogenosomes.
AB  - Lateral gene transfer (LGT) is an important mechanism of evolution for protists
      adapting to oxygen-poor environments. Specifically, modifications of energy
      metabolism in anaerobic forms of mitochondria (e.g., hydrogenosomes) are likely
      to have been associated with gene transfer from prokaryotes. An interesting
      question is whether the products of transferred genes were directly targeted into
      the ancestral organelle or initially operated in the cytosol and subsequently
      acquired organelle-targeting sequences. Here, we identified key enzymes of
      hydrogenosomal metabolism in the free-living anaerobic amoebozoan Mastigamoeba
      balamuthi and analyzed their cellular localizations, enzymatic activities, and
      evolutionary histories. Additionally, we characterized 1) several canonical
      mitochondrial components including respiratory complex II and the glycine
      cleavage system, 2) enzymes associated with anaerobic energy metabolism,
      including an unusual D-lactate dehydrogenase and acetyl CoA synthase, and 3) a
      sulfate activation pathway. Intriguingly, components of anaerobic energy
      metabolism are present in at least two gene copies. For each component, one copy
      possesses an mitochondrial targeting sequence (MTS), whereas the other lacks an
      MTS, yielding parallel cytosolic and hydrogenosomal extended glycolysis pathways.
      Experimentally, we confirmed that the organelle targeting of several proteins is
      fully dependent on the MTS. Phylogenetic analysis of all extended glycolysis
      components suggested that these components were acquired by LGT. We propose that
      the transformation from an ancestral organelle to a hydrogenosome in the M.
      balamuthi lineage involved the lateral acquisition of genes encoding extended
      glycolysis enzymes that initially operated in the cytosol and that established a
      parallel hydrogenosomal pathway after gene duplication and MTS acquisition. 

PMID- 25573907
TI  - Comparative toxicity evaluation of flower-shaped and spherical gold nanoparticles
      on human endothelial cells.
AB  - In this paper, we propose a multi-parametric in vitro study of the cytotoxicity
      of gold nanoparticles (GNPs) on human endothelial cell (HUVEC). The cytotoxicity
      is evaluated by incubating cells with six different GNP types which have two
      different morphologies: spherical and flower-shaped, two sizes (~15 and ~50 nm
      diameter) and two surface chemistries (as prepared form and PEGylated form). Our
      results showed that by increasing the concentration of GNPs the cell viability
      decreases with a toxic concentration threshold of 10 pM for spherical GNPs and of
      1 pM for flower-shaped GNPs. Dark field images, flow cytometry and spreading test
      revealed that flower-shaped GNPs have more deleterious effects on the cell
      mechanisms than spherical GNPs. We demonstrated that the main parameter in the
      evaluation of the GNPs toxicity is the GNPs roughness and that this effect is
      independent on the surface chemistry. We assume that this behavior is highly
      related to the efficiency of the GNPs internalization within the cells and that
      this effect is enhanced due to the specific geometry of the flower-shaped GNPs. 

PMID- 25573911
TI  - A multi-journal partnership to highlight joint first-authors of manuscripts.

PMID- 25573912
TI  - Determination of the static spring constant of electrically-driven quartz tuning
      forks with two freely oscillating prongs.
AB  - Quartz tuning forks have become popular in nanotechnology applications,
      especially as sensors for scanning probe microscopy. The sensor's spring constant
      and the oscillation amplitude are required parameters to evaluate the tip-sample
      forces; however, there is certain controversy within the research community as to
      how to arrive at a value for the static spring constant of the device when
      working in shear mode. Here, we present two different methods based on finite
      element simulations, to determine the value of the spring constant of the
      sensors: the amplitude and Cleveland methods. The results obtained using these
      methods are compared to those using the geometrical method, and show that the
      latter overestimates the spring constant of the device. 

PMID- 25573910
TI  - Apolipoprotein L1-associated nephropathy and the future of renal diagnostics.

PMID- 25573908
TI  - Clinical Features and Histology of Apolipoprotein L1-Associated Nephropathy in
      the FSGS Clinical Trial.
AB  - Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We
      sought to better define the phenotype of APOL1-associated nephropathy. The FSGS
      Clinical Trial involved 138 children and young adults who were randomized to
      cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary
      outcome of proteinuria remission. DNA was available from 94 subjects who were
      genotyped for APOL1 renal risk variants, with two risk alleles comprising the
      risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four
      subjects did not self-identify as African American, and 23 of 32 (72%) self
      identified African Americans. Individuals with the APOL1 risk genotype tended to
      present at an older age and had significantly lower baseline eGFR, more segmental
      glomerulosclerosis and total glomerulosclerosis, and more tubular
      atrophy/interstitial fibrosis. There were differences in renal histology,
      particularly more collapsing variants in those with the risk genotype (P=0.02),
      although this association was confounded by age. APOL1 risk genotype did not
      affect response to either treatment regimen. Individuals with the risk genotype
      were more likely to progress to ESRD (P<0.01). In conclusion, APOL1 risk
      genotypes are common in African-American subjects with primary FSGS and may also
      be present in individuals who do not self-identify as African American. APOL1
      risk status is associated with lower kidney function, more glomerulosclerosis and
      interstitial fibrosis, and greater propensity to progress to ESRD. The APOL1 risk
      genotype did not influence proteinuria responses to cyclosporin or mycophenolate
      mofetil/dexamethasone. 

PMID- 25573909
TI  - Complement Factor C4d Is a Common Denominator in Thrombotic Microangiopathy.
AB  - Complement activation has a major role in thrombotic microangiopathy (TMA), a
      disorder that can occur in a variety of clinical conditions. Promising results of
      recent trials with terminal complement-inhibiting drugs call for biomarkers
      identifying patients who might benefit from this treatment. The primary aim of
      this study was to determine the prevalence and localization of complement factor
      C4d in kidneys of patients with TMA. The secondary aims were to determine which
      complement pathways lead to C4d deposition and to determine whether complement
      activation results in deposition of the terminal complement complex. We examined
      42 renal sections with histologically confirmed TMA obtained from a heterogeneous
      patient group. Deposits of C4d, mannose-binding lectin, C1q, IgM, and C5b-9 were
      scored in the glomeruli, peritubular capillaries, and arterioles. Notably, C4d
      deposits were present in 88.1% of TMA cases, and the various clinical conditions
      had distinct staining patterns within the various compartments of the renal
      vasculature. Classical pathway activation was observed in 90.5% of TMA cases. C5b
      9 deposits were present in 78.6% of TMA cases and in 39.6% of controls (n=53),
      but the staining pattern differed between cases and controls. In conclusion, C4d
      is a common finding in TMA, regardless of the underlying clinical condition.
      Moreover, C5b-9 was present in >75% of the TMA samples, suggesting that terminal
      complement inhibitors may have a beneficial effect in these patients. C4d and C5b
      9 should be investigated as possible diagnostic biomarkers in the clinical work
      up of patients suspected of having complement-mediated TMA. 

PMID- 25573913
TI  - Integrating alignment-based and alignment-free sequence similarity measures for
      biological sequence classification.
AB  - MOTIVATION: Alignment-based sequence similarity searches, while accurate for some
      type of sequences, can produce incorrect results when used on more divergent but
      functionally related sequences that have undergone the sequence rearrangements
      observed in many bacterial and viral genomes. Here, we propose a classification
      model that exploits the complementary nature of alignment-based and alignment
      free similarity measures with the aim to improve the accuracy with which DNA and
      protein sequences are characterized. RESULTS: Our model classifies sequences
      using a combined sequence similarity score calculated by adaptively weighting the
      contribution of different sequence similarity measures. Weights are determined
      independently for each sequence in the test set and reflect the discriminatory
      ability of individual similarity measures in the training set. Because the
      similarity between some sequences is determined more accurately with one type of
      measure rather than another, our classifier allows different sets of weights to
      be associated with different sequences. Using five different similarity measures,
      we show that our model significantly improves the classification accuracy over
      the current composition- and alignment-based models, when predicting the
      taxonomic lineage for both short viral sequence fragments and complete viral
      sequences. We also show that our model can be used effectively for the
      classification of reads from a real metagenome dataset as well as protein
      sequences. AVAILABILITY AND IMPLEMENTATION: All the datasets and the code used in
      this study are freely available at
      https://collaborators.oicr.on.ca/vferretti/borozan_csss/csss.html. CONTACT:
      ivan.borozan@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 25573915
TI  - DDIG-in: detecting disease-causing genetic variations due to frameshifting indels
      and nonsense mutations employing sequence and structural properties at nucleotide
      and protein levels.
AB  - MOTIVATION: Frameshifting (FS) indels and nonsense (NS) variants disrupt the
      protein-coding sequence downstream of the mutation site by changing the reading
      frame or introducing a premature termination codon, respectively. Despite such
      drastic changes to the protein sequence, FS indels and NS variants have been
      discovered in healthy individuals. How to discriminate disease-causing from
      neutral FS indels and NS variants is an understudied problem. RESULTS: We have
      built a machine learning method called DDIG-in (FS) based on real human genetic
      variations from the Human Gene Mutation Database (inherited disease-causing) and
      the 1000 Genomes Project (GP) (putatively neutral). The method incorporates both
      sequence and predicted structural features and yields a robust performance by 10
      fold cross-validation and independent tests on both FS indels and NS variants. We
      showed that human-derived NS variants and FS indels derived from animal orthologs
      can be effectively employed for independent testing of our method trained on
      human-derived FS indels. DDIG-in (FS) achieves a Matthews correlation coefficient
      (MCC) of 0.59, a sensitivity of 86%, and a specificity of 72% for FS indels.
      Application of DDIG-in (FS) to NS variants yields essentially the same
      performance (MCC of 0.43) as a method that was specifically trained for NS
      variants. DDIG-in (FS) was shown to make a significant improvement over existing
      techniques.

PMID- 25573914
TI  - Inferring single-cell gene expression mechanisms using stochastic simulation.
AB  - MOTIVATION: Stochastic promoter switching between transcriptionally active (ON)
      and inactive (OFF) states is a major source of noise in gene expression. It is
      often implicitly assumed that transitions between promoter states are memoryless,
      i.e. promoters spend an exponentially distributed time interval in each of the
      two states. However, increasing evidence suggests that promoter ON/OFF times can
      be non-exponential, hinting at more complex transcriptional regulatory
      architectures. Given the essential role of gene expression in all cellular
      functions, efficient computational techniques for characterizing promoter
      architectures are critically needed. RESULTS: We have developed a novel model
      reduction for promoters with arbitrary numbers of ON and OFF states, allowing us
      to approximate complex promoter switching behavior with Weibull-distributed
      ON/OFF times. Using this model reduction, we created bursty Monte Carlo
      expectation-maximization with modified cross-entropy method ('bursty MCEM(2)'),
      an efficient parameter estimation and model selection technique for inferring the
      number and configuration of promoter states from single-cell gene expression
      data. Application of bursty MCEM(2) to data from the endogenous mouse glutaminase
      promoter reveals nearly deterministic promoter OFF times, consistent with a multi
      step activation mechanism consisting of 10 or more inactive states. Our novel
      approach to modeling promoter fluctuations together with bursty MCEM(2) provides
      powerful tools for characterizing transcriptional bursting across genes under
      different environmental conditions. AVAILABILITY AND IMPLEMENTATION: R source
      code implementing bursty MCEM(2) is available upon request. CONTACT:
      absingh@udel.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 25573916
TI  - Combining tree-based and dynamical systems for the inference of gene regulatory
      networks.
AB  - MOTIVATION: Reconstructing the topology of gene regulatory networks (GRNs) from
      time series of gene expression data remains an important open problem in
      computational systems biology. Existing GRN inference algorithms face one of two
      limitations: model-free methods are scalable but suffer from a lack of
      interpretability and cannot in general be used for out of sample predictions. On
      the other hand, model-based methods focus on identifying a dynamical model of the
      system. These are clearly interpretable and can be used for predictions; however,
      they rely on strong assumptions and are typically very demanding computationally.
      RESULTS: Here, we propose a new hybrid approach for GRN inference, called Jump3,
      exploiting time series of expression data. Jump3 is based on a formal on/off
      model of gene expression but uses a non-parametric procedure based on decision
      trees (called 'jump trees') to reconstruct the GRN topology, allowing the
      inference of networks of hundreds of genes. We show the good performance of Jump3
      on in silico and synthetic networks and applied the approach to identify
      regulatory interactions activated in the presence of interferon gamma.

PMID- 25573917
TI  - PVAAS: identify variants associated with aberrant splicing from RNA-seq.
AB  - MOTIVATION: RNA-seq has been widely used to study the transcriptome. Comparing to
      microarray, sequencing-based RNA-seq is able to identify splicing variants and
      single nucleotide variants in one experiment simultaneously. This provides unique
      opportunity to detect variants that associated with aberrant splicing. Despite
      the popularity of RNA-seq, no bioinformatics tool has been developed to leverage
      this advantage to identify variants associated with aberrant splicing. RESULTS:
      We have developed PVAAS, a tool to identify single nucleotide variants that
      associated with aberrant alternative splicing from RNA-seq data. PVAAS works in
      three steps: (i) identify aberrant splicings; (ii) use user-provided variants or
      perform variant calling; (iii) assess the significance of association between
      variants and aberrant splicing events.

PMID- 25573918
TI  - LINKPHASE3: an improved pedigree-based phasing algorithm robust to genotyping and
      map errors.
AB  - Many applications in genetics require haplotype reconstruction. We present a
      phasing program designed for large half-sibs families (as observed in plant and
      animals) that is robust to genotyping and map errors. We demonstrate that it is
      more efficient than previous versions and other programs, particularly in the
      presence of genotyping errors.

PMID- 25573919
TI  - RNA-Rocket: an RNA-Seq analysis resource for infectious disease research.
AB  - MOTIVATION: RNA-Seq is a method for profiling transcription using high-throughput
      sequencing and is an important component of many research projects that wish to
      study transcript isoforms, condition specific expression and transcriptional
      structure. The methods, tools and technologies used to perform RNA-Seq analysis
      continue to change, creating a bioinformatics challenge for researchers who wish
      to exploit these data. Resources that bring together genomic data, analysis
      tools, educational material and computational infrastructure can minimize the
      overhead required of life science researchers. RESULTS: RNA-Rocket is a free
      service that provides access to RNA-Seq and ChIP-Seq analysis tools for studying
      infectious diseases. The site makes available thousands of pre-indexed genomes,
      their annotations and the ability to stream results to the bioinformatics
      resources VectorBase, EuPathDB and PATRIC. The site also provides a combination
      of experimental data and metadata, examples of pre-computed analysis, step-by
      step guides and a user interface designed to enable both novice and experienced
      users of RNA-Seq data. AVAILABILITY AND IMPLEMENTATION: RNA-Rocket is available
      at rnaseq.pathogenportal.org. Source code for this project can be found at
      github.com/cidvbi/PathogenPortal. CONTACT: anwarren@vt.edu SUPPLEMENTARY
      INFORMATION: Supplementary materials are available at Bioinformatics online.

PMID- 25573920
TI  - Acquire: an open-source comprehensive cancer biobanking system.
AB  - MOTIVATION: The probability of effective treatment of cancer with a targeted
      therapeutic can be improved for patients with defined genotypes containing
      actionable mutations. To this end, many human cancer biobanks are integrating
      more tightly with genomic sequencing facilities and with those creating and
      maintaining patient-derived xenografts (PDX) and cell lines to provide renewable
      resources for translational research. RESULTS: To support the complex data
      management needs and workflows of several such biobanks, we developed Acquire. It
      is a robust, secure, web-based, database-backed open-source system that supports
      all major needs of a modern cancer biobank. Its modules allow for i) up-to-the
      minute 'scoreboard' and graphical reporting of collections; ii) end user roles
      and permissions; iii) specimen inventory through caTissue Suite; iv) shipping
      forms for distribution of specimens to pathology, genomic analysis and PDX/cell
      line creation facilities; v) robust ad hoc querying; vi) molecular and cellular
      quality control metrics to track specimens' progress and quality; vii) public
      researcher request; viii) resource allocation committee distribution request
      review and oversight and ix) linkage to available derivatives of specimen.

PMID- 25573921
TI  - Using isoelectric point to determine the pH for initial protein crystallization
      trials.
AB  - MOTIVATION: The identification of suitable conditions for crystallization is a
      rate-limiting step in protein structure determination. The pH of an experiment is
      an important parameter and has the potential to be used in data-mining studies to
      help reduce the number of crystallization trials required. However, the pH is
      usually recorded as that of the buffer solution, which can be highly inaccurate.
      RESULTS: Here, we show that a better estimate of the true pH can be predicted by
      considering not only the buffer pH but also any other chemicals in the
      crystallization solution. We use these more accurate pH values to investigate the
      disputed relationship between the pI of a protein and the pH at which it
      crystallizes. AVAILABILITY AND IMPLEMENTATION: Data used to generate models are
      available as Supplementary Material. CONTACT: julie.wilson@york.ac.uk
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 25573922
TI  - MADGiC: a model-based approach for identifying driver genes in cancer.
AB  - MOTIVATION: Identifying and prioritizing somatic mutations is an important and
      challenging area of cancer research that can provide new insights into gene
      function as well as new targets for drug development. Most methods for
      prioritizing mutations rely primarily on frequency-based criteria, where a gene
      is identified as having a driver mutation if it is altered in significantly more
      samples than expected according to a background model. Although useful, frequency
      based methods are limited in that all mutations are treated equally. It is well
      known, however, that some mutations have no functional consequence, while others
      may have a major deleterious impact. The spatial pattern of mutations within a
      gene provides further insight into their functional consequence. Properly
      accounting for these factors improves both the power and accuracy of inference.
      Also important is an accurate background model. RESULTS: Here, we develop a Model
      based Approach for identifying Driver Genes in Cancer (termed MADGiC) that
      incorporates both frequency and functional impact criteria and accommodates a
      number of factors to improve the background model. Simulation studies demonstrate
      advantages of the approach, including a substantial increase in power over
      competing methods. Further advantages are illustrated in an analysis of ovarian
      and lung cancer data from The Cancer Genome Atlas (TCGA) project.

PMID- 25573924
TI  - Optically transparent and environmentally durable superhydrophobic coating based
      on functionalized SiO2 nanoparticles.
AB  - Optical surfaces such as mirrors and windows that are exposed to outdoor
      environmental conditions are susceptible to dust buildup and water condensation.
      The application of transparent superhydrophobic coatings on optical surfaces can
      improve outdoor performance via a 'self-cleaning' effect similar to the Lotus
      effect. The contact angle (CA) of water droplets on a typical hydrophobic flat
      surface varies from 100 degrees  to 120 degrees . Adding roughness or
      microtexture to a hydrophobic surface leads to an enhancement of hydrophobicity
      and the CA can be increased to a value in the range of 160 degrees -175 degrees .
      This result is remarkable because such behavior cannot be explained using surface
      chemistry alone. When surface features are on the order of 100 nm or smaller,
      they exhibit superhydrophobic behavior and maintain their optical transparency.
      In this work we discuss our results on transparent superhydrophobic coatings that
      can be applied across large surface areas. We have used functionalized silica
      nanoparticles to coat various optical elements and have measured the CA and
      optical transmission between 190 and 1100 nm on these elements. The
      functionalized silica nanoparticles were dissolved in a solution of the solvents,
      while the binder used was a polyurethane clearcoat. This solution was spin-coated
      onto a variety of test glass substrates, and following a curing period of about
      30 min, these coatings exhibited superhydrophobic behavior with a static CA >=
      160 degrees . 

PMID- 25573923
TI  - Self-assembly of nanoparticles onto the surfaces of polystyrene spheres with a
      tunable composition and loading.
AB  - Functional colloidal materials were prepared by design through the self-assembly
      of nanoparticles (NPs) on the surfaces of polystyrene (PS) spheres with control
      over NP surface coverage, NP-to-NP spacing, and NP composition. The ability to
      control and fine tune the coating was extended to the first demonstration of the
      co-assembly of NPs of dissimilar composition onto the same PS sphere, forming a
      multi-component coating. A broad range of NP decorated PS (PS@NPs) spheres were
      prepared with uniform coatings attributed to electrostatic and hydrogen bonding
      interactions between stabilizing groups on the NPs and the functionalized
      surfaces of the PS spheres. This versatile two-step method provides more fine
      control than methods previously demonstrated in the literature. These decorated
      PS spheres are of interest for a number of applications, such as catalytic
      reactions where the PS spheres provide a support for the dispersion,
      stabilization, and recovery of NP catalysts. The catalytic properties of these
      PS@NPs spheres were assessed by studying the catalytic degradation of azo dyes,
      an environmental contaminant detrimental to eye health. The PS@NPs spheres were
      used in multiple, sequential catalytic reactions while largely retaining the NP
      coating. 

PMID- 25573925
TI  - Draft Genome Sequence of Sphingomonas sp. Strain Ant20, Isolated from Oil
      Contaminated Soil on Ross Island, Antarctica.
AB  - Here, we present the draft genome of Sphingomonas sp. strain Ant20, isolated from
      oil-polluted soil near Scott Base, Ross Island, Antarctica. The genome of this
      aromatic hydrocarbon-degrading bacterium provides valuable information on the
      microbially mediated biodegradation of aromatic compounds in cold-climate
      systems. 

PMID- 25573927
TI  - Complete Genome Sequence of the Fish Pathogen Yersinia ruckeri Strain SC09,
      Isolated from Diseased Ictalurus punctatus in China.
AB  - Yersinia ruckeri SC09 is a Gram-negative bacterium isolated from a moribund
      Ictalurus punctatus collected in Jianyang, China. Here, we report the complete
      genome sequence of this microorganism to facilitate the investigation of its
      pathogenicity and to reevaluate its taxonomic position. 

PMID- 25573926
TI  - Draft Genome Sequence of the Extremely Halophilic Bacterium Halomonas salina
      Strain CIFRI1, Isolated from the East Coast of India.
AB  - Halomonas salina strain CIFRI1 is an extremely salt-stress-tolerant bacterium
      isolated from the salt crystals of the east coast of India. Here we report the
      annotated 3.45-Mb draft genome sequence of strain CIFRI1 having 86 contigs with
      3,139 protein coding loci, including 62 RNA genes. 

PMID- 25573930
TI  - Draft Genome Sequence of Bordetella trematum Strain HR18.
AB  - The genus Bordetella is reportedly a human or animal pathogen and environmental
      microbe. We report the draft genome sequence of Bordetella trematum strain HR18,
      which was isolated from the rumen of Korean native cattle (Hanwoo; Bos taurus
      coreanae). It is the first genome sequence of a Bordetella sp. isolated from the
      rumen of cattle. 

PMID- 25573928
TI  - Draft Genome Sequences of Vibrio fluvialis Strains 560 and 539, Isolated from
      Environmental Samples.
AB  - Vibrio fluvialis is a halophilic bacterium found in many environments and is
      mainly associated with sporadic cases and outbreaks of gastroenteritis in humans.
      Here, we describe the genome sequences of environmental strains of V. fluvialis
      560 (Vf560) and V. fluvialis 539 (Vf539) possessing a variant of the integrative
      and conjugative element (ICE) SXT for the first time in Brazil and South America.

PMID- 25573929
TI  - Genome sequence of a novel recombinant coxsackievirus a6 strain from shanghai,
      china, 2013.
AB  - A novel recombinant coxsackievirus A6 (CVA6) strain was isolated during a
      coxsackievirus A6 outbreak in Shanghai, China, in 2013. Genomic sequence and
      similarity plot analysis showed that the novel CVA6 strain shared higher
      similarity with a recent CVA4 strain rather than the recent CVA6 strain in the 2C
      and 3' untranslated regions (UTRs). 

PMID- 25573931
TI  - Draft Genome Sequence of Acinetobacter sp. HR7, Isolated from Hanwoo, Korean
      Native Cattle.
AB  - Acinetobacter species have been reported as opportunistic pathogens. Here, we
      report the draft genome sequence of Acinetobacter sp. HR7 isolated from the rumen
      of cannulated Korean native cattle (Hanwoo; Bos taurus coreanae). 

PMID- 25573932
TI  - Complete genome sequence of porcine parvovirus N strain isolated from guangxi,
      china.
AB  - We report here the complete genomic sequence of the porcine parvovirus (PPV) N
      strain, isolated in 1989 from the viscera of a stillborn fetus farrowed by a gilt
      in Guangxi, southern China. Phylogenetic analyses suggest that the PPV-N strain
      is closely related to attenuated PPV NADL-2 strains. The PPV-N strain has good
      immunogenicity, genetic stability, and safety. 

PMID- 25573933
TI  - Complete Genome Sequence of Bacillus amyloliquefaciens subsp. plantarum CC178, a
      Phyllosphere Bacterium Antagonistic to Plant Pathogenic Fungi.
AB  - Bacillus amyloliquefaciens subsp. plantarum strain CC178 is a phyllosphere
      bacterium with antagonistic activity against a wide range of plant fungal
      pathogens. The genome of strain CC178 is 3,916,828 bp in size and harbors 3,972
      genes. Six giant gene clusters are dedicated to the nonribosomal synthesis of
      antimicrobial polypeptides and polyketides. 

PMID- 25573934
TI  - Complete Genome Sequence of Human Enterovirus Strain 71 (EV71/Taipei/3118/2011),
      Isolated from a Patient in Taiwan.
AB  - This full-length genome sequence of human enterovirus strain 71
      (EV71/Taipei/3118/2011) was isolated from a clinical patient in Taiwan in 2011.
      According to the phylogenetic analysis, the complete genome sequence in this
      study is part of the subgenotype C4. 

PMID- 25573935
TI  - Draft Genome Sequence of Legionella pneumophila D-5864, a Serogroup 6 Strain.
AB  - Legionella pneumophila is the leading etiology of legionellosis infections in
      North America and Europe. Here we report the draft genome sequence of L.
      pneumophila D-5864, a serogroup 6 strain, which was isolated from a bronchial
      alveolar lavage specimen of a male patient from Arizona in 2009. Genes within the
      lipopolysaccharide (LPS)-biosynthesis region could potentially be determinants of
      serogroup specificity. 

PMID- 25573936
TI  - Complete Genome Sequence of VpKK5, a Novel Vibrio parahaemolyticus Lytic
      Siphophage.
AB  - This paper describes the complete sequence of a novel lytic marine siphophage,
      VpKK5, that is specific to Vibrio parahemolyticus. 

PMID- 25573937
TI  - Draft genome sequences of six type strains of the genus streptacidiphilus.
AB  - Members of the genus Streptacidiphilus are acidophilic actinomycetes with
      streptomycete-like features. Here, we report the draft genome sequences of the
      type strains of Streptacidiphilus albus, Streptacidiphilus anmyonensis,
      Streptacidiphilus carbonis, Streptacidiphilus jiangxiensis, Streptacidiphilus
      melanogenes, and Streptacidiphilus neutrinimicus. These genome sequences will
      serve as valuable references for understanding their taxonomic relationships,
      genetic characteristics, and potentials for industry. 

PMID- 25573938
TI  - Genome Sequence of Thermoactinomyces daqus H-18, a Novel Thermophilic Species
      Isolated from High-Temperature Daqu.
AB  - Thermoactinomyces daqus H-18 is a new species of Thermoactinomyces isolated from
      high-temperature Daqu used in the fermentation of Bandongjing sesame-flavor
      liquor. Its genome was sequenced and assembled (3.44 Mb). The coding sequences
      (CDSs) that correlated to high-temperature tolerance were annotated. The
      metabolic pathways for the compounds responsible for flavor were also found. 

PMID- 25573939
TI  - Genome Sequence of an Extensively Drug-Resistant Strain of Klebsiella pneumoniae,
      Strain YN-1, with Carbapenem Resistance.
AB  - The emergence and spread of multidrug-resistant (MDR) Klebsiella pneumoniae has
      been regarded as one of the major challenges among health care-associated
      infections worldwide. Here, we report the draft genome sequence of an extensively
      drug-resistant (XDR) K. pneumoniae strain isolated in 2013 from Yunnan Province,
      China. 

PMID- 25573940
TI  - Complete Genome Sequences of Citrobacter braakii Strains GTA-CB01 and GTA-CB04,
      Isolated from Ground Beef.
AB  - Citrobacter braakii is a Gram-negative bacterium belonging to the
      Enterobacteriaceae family. Here, we report 5.2- and 5.0-Mb genome assemblies for
      C. braakii strains GTA-CB01 and GTA-CB04, respectively. 

PMID- 25573942
TI  - Complete Genome Sequence of Steroid-Transforming Nocardioides simplex VKM Ac
      2033D.
AB  - Nocardioides simplex VKM Ac-2033D is an effective microbial catalyst for 3
      ketosteroid 1(2)-dehydrogenation, and it is capable of effective reduction of
      carbonyl groups at C-17 and C-20, hydrolysis of acetylated steroids, and
      utilization of natural sterols. Here, the complete genome sequence is reported.
      An array of genes related to steroid metabolic pathways have been identified. 

PMID- 25573941
TI  - Draft Genome Sequences of Two Drug-Resistant Isolates of Pseudomonas aeruginosa
      Obtained from Keratitis Patients in India.
AB  - We report here the draft genomes of two drug (fluoroquinolone)-resistant clinical
      isolates of Pseudomonas aeruginosa obtained from the corneal scrapings of
      keratitis patients from India. The two annotated genomes are 6.31 Mb and 6.41 Mb
      in size. These genomes are expected to facilitate the identification and
      understanding of the genes associated with acquired multidrug resistance. 

PMID- 25573943
TI  - Finished Genome Sequence of Collimonas arenae Cal35.
AB  - We announce the finished genome sequence of soil forest isolate Collimonas arenae
      Cal35, which comprises a 5.6-Mbp chromosome and 41-kb plasmid. The Cal35 genome
      is the second one published for the bacterial genus Collimonas and represents the
      first opportunity for high-resolution comparison of genome content and synteny
      among collimonads. 

PMID- 25573945
TI  - Draft Genome Sequence of Anammox Bacterium "Candidatus Scalindua brodae,"
      Obtained Using Differential Coverage Binning of Sequencing Data from Two Reactor
      Enrichments.
AB  - We present the draft genome of anammox bacterium "Candidatus Scalindua brodae,"
      which at 282 contigs is a major improvement over the highly fragmented genome
      assembly of related species "Ca. Scalindua profunda" (1,580 contigs) which was
      previously published. 

PMID- 25573944
TI  - Draft Genome Sequence of Actinoplanes utahensis NRRL 12052, a Microorganism
      Involved in Industrial Production of Pharmaceutical Intermediates.
AB  - Here, we describe the draft genome sequence of Actinoplanes utahensis NRRL 12052,
      a filamentous bacterium that encodes an aculeacin A acylase and a putative N-acyl
      homoserine lactone acylase of biotechnological interest. Moreover, several
      nonribosomal peptide synthase (NRPS) and polyketide synthase (PKS) clusters and
      antibiotic resistance genes have been identified. 

PMID- 25573946
TI  - Impact of Co-management at the Primary-Subspecialty Care Interface on Follow-up
      and Referral Patterns for Patients With Concussion.
AB  - BACKGROUND: Co-management is a collaborative care model that consists of
      structured tools to define and document care delivered by 2 or more providers. We
      evaluated the impact of implementing co-management at the interface between
      pediatric primary care providers (PCPs) and subspecialists. METHODS:
      Participating PCPs (n = 9) were trained on management of concussion using the co
      management tools. Co-managed patients with concussion were prospectively enrolled
      (n = 148) and compared to a retrospective audit of non-co-managed patients (n =
      50). RESULTS: PCPs using co-management demonstrated adherence to the tools. PCPs
      were significantly more likely to provide follow-up care to patients when using
      the co-management tools. All participating PCPs reported that co-management
      enhanced their expertise in caring for patients with concussion. CONCLUSIONS: Co
      management can enhance PCPs' capacity to independently manage the care of
      patients with concussion. Co-management led to an observed change in practice
      that merits further exploration in terms of cost, quality, and clinical outcomes.

PMID- 25573948
TI  - Guideline-Concordant Treatment of Kawasaki Disease With Immunoglobulin and
      Aspirin and the Incidence of Coronary Artery Aneurysm.
AB  - OBJECTIVE: Current guidelines for Kawasaki disease (KD) recommend intravenous
      immunoglobulin infusion and echocardiography. However, no previous studies have
      evaluated the relationship between the treating hospital's concordance with
      guidelines and the prevention of coronary artery aneurysm in patients with KD.
      STUDY DESIGN: KD patients between 2010 and 2013 were identified in a Japanese
      national inpatient database. Guideline concordance was defined as the proportions
      of patients who received echocardiography as well as treatment with both
      immunoglobulin and aspirin, which were divided into quartiles. Multivariable
      logistic regression analysis was conducted to examine the association between the
      guideline concordance and the occurrence of coronary artery aneurysm with
      adjustment for patient backgrounds. RESULTS: In sum, 20 156 patients with KD were
      identified. The very high (>83.3%) concordance group had a lower rate of coronary
      artery aneurysm than the very low (<59.0%) concordance group (4.9% vs 9.9%; odds
      ratio, 0.45; 95% CI, 0.27 to 0.74; P = .002). CONCLUSION: All patients with KD
      should be treated according to the guidelines.

PMID- 25573947
TI  - Validation of Parent-Reported Injuries to Their Children.
AB  - OBJECTIVE: Injury is a leading cause of emergency department visits, disability,
      and death in children. This study examined the sensitivity and specificity of
      parental report of children's specific injuries. METHODS: A prospective
      validation study was conducted in 3 urban pediatric emergency departments from
      August 2010 to July 2011. Parents of injured children completed a survey at 2
      weeks following the emergency department visit, and their responses were compared
      to injury data that were abstracted from medical records. RESULTS: Parent surveys
      were completed for 516 injured children. Sensitivities were >=0.75 for all
      fractures and >=0.88 for extremity and skull fractures. Internal organ injuries
      were generally less accurately reported by parents than fractures. Specificity
      estimates all exceeded 0.95. CONCLUSIONS: This telephone-administered and mailed
      self-administered survey enabled parents to accurately report specific head and
      extremity injuries. PRACTICAL APPLICATIONS: This survey may be a useful tool for
      pediatric injury surveillance activities.

PMID- 25573949
TI  - Vaccine Responses and Immunologic Characteristics of Pediatric Patients With
      DiGeorge Syndrome.

PMID- 25573950
TI  - Comparison of abdominal ultrasound, endoscopic ultrasound and magnetic resonance
      imaging in detection of necrotic debris in walled-off pancreatic necrosis.
AB  - BACKGROUND: Walled-off pancreatic necrosis (WOPN) is an important complication of
      acute pancreatitis that is diagnosed by imaging modalities such as endoscopic
      ultrasound (EUS) or magnetic resonance imaging (MRI), which can clearly visualize
      necrotic debris. The effectiveness of abdominal ultrasound (USG) in detecting
      solid debris in WOPN is not clear. METHODS: A total of 52 patients (37 males,
      mean age 38.9 +/- 12.6 years) with symptomatic WOPN were prospectively studied
      using EUS, MRI and USG. These investigations were done at a mean of 11.7 +/- 5.5
      weeks of onset of acute pancreatitis and within two days. RESULTS: WOPN was
      detected by EUS & MRI in all patients, whereas USG could not detect it in 4
      (7.6%) patients (3 had predominantly solid WOPN, whereas one had air foci in
      WOPN). USG, MRI and EUS could detect solid debris in all patients with detectable
      WOPN. EUS and USG detected <10% debris in 10 (20%) patients, whereas MRI detected
      <10% debris in 14 (27%) patients. EUS and USG detected 10-40% debris in 33
      patients whereas MRI detected 10-40% debris in 30 (58%) patients. More than 40%
      debris was better characterized on EUS and MRI with both detecting >40% debris in
      8 patients (15%) compared to 5 (11%) patients having >40% debris on USG. EUS
      detected collaterals around WOPN that were not detected on USG or MRI.
      CONCLUSION: USG can characterize the majority of WOPN, with accuracy comparable
      to that of EUS/MRI. However its limitations are the inability to detect
      collaterals around WOPN and characterize collections with high solid content or
      air.

PMID- 25573951
TI  - Autophagy Supports Breast Cancer Stem Cell Maintenance by Regulating IL6
      Secretion.
AB  - Autophagy is a mechanism by which cells degrade cellular material to provide
      nutrients and energy for survival during stress. The autophagy is thought to be a
      critical process for cancer stem cell (CSC) or tumor-initiating cell maintenance
      but the mechanisms by which autophagy supports survival of CSCs remain poorly
      understood. In this study, inhibition of autophagy by knockdown of ATG7 or BECN1
      modified the CD44(+)/CD24(low/-) population in breast cancer cells by regulating
      CD24 and IL6 secretion. In a breast cancer cell line that is independent of
      autophagy for survival, autophagy inhibition increased IL6 secretion to the
      media. On the other hand, in an autophagy-dependent cell line, autophagy
      inhibition decreased IL6 secretion, cell survival, and mammosphere formation. In
      these cells, IL6 treatment or conditioned media from autophagy-competent cells
      rescued the deficiency in mammosphere formation induced by autophagy inhibition.
      These results reveal that autophagy regulates breast CSC maintenance in autophagy
      dependent breast cancer cells by modulating IL6 secretion implicating autophagy
      as a potential therapeutic target in breast cancer. IMPLICATIONS: Modulation of
      autophagy in breast cancer has different and even opposite effects, indicating
      the need for a selection strategy when trying to manipulate autophagy in the
      context of cancer therapy.

PMID- 25573952
TI  - Mutant p53 Amplifies Epidermal Growth Factor Receptor Family Signaling to Promote
      Mammary Tumorigenesis.
AB  - The EGFR family (ErbB2/Her2 and EGFR/ErbB1/Her1) often modulates the
      transcriptional program involved in promoting mammary tumorigenesis. In humans,
      the majority of ErbB2-positive sporadic breast cancers harbor p53 mutations,
      which correlate with poor prognosis. Also, the extremely high incidence of ErbB2
      positive breast cancer in women with p53 germline mutations (Li-Fraumeni
      syndrome) suggests a key role of mutant p53 specifically in ErbB2-mediated
      mammary tumorigenesis. To examine the role of mutant p53 during ErbB2-mediated
      mammary tumorigenesis, a mutant p53 allele (R172H) was introduced into the (MMTV)
      ErbB2/Neu mouse model system. Interestingly, we show in heterozygous p53 mice
      that mutant p53 R172H is a more potent activator of ErbB2-mediated mammary
      tumorigenesis than simple loss of p53. The more aggressive disease in mutant p53
      animals was reflected by earlier tumor onset, increased mammary tumor
      multiplicity, and shorter survival. These in vivo and in vitro data provide
      mechanistic evidence that mutant p53 amplifies ErbB2 and EGFR signaling to
      promote the expansion of mammary stem cells and induce cell proliferation.
      IMPLICATIONS: This study identifies mutant p53 as an essential player in ErbB2
      and EGFR-mediated mammary tumorigenesis and indicates the potential translational
      importance of targeting mutant p53 in this subset of patients with breast cancer.

PMID- 25573953
TI  - Systematic siRNA Screen Unmasks NSCLC Growth Dependence by Palmitoyltransferase
      DHHC5.
AB  - Protein S-palmitoylation is a widespread and dynamic posttranslational
      modification that regulates protein-membrane interactions, protein-protein
      interactions, and protein stability. A large family of palmitoyl acyl
      transferases, termed the DHHC family due to the presence of a common catalytic
      motif, catalyzes S-palmitoylation; the role of these enzymes in cancer is largely
      unexplored. In this study, an RNAi-based screen targeting all 23 members of the
      DHHC family was conducted to examine the effects on the growth in non-small cell
      lung cancer (NSCLC). Interestingly, siRNAs directed against DHHC5 broadly
      inhibited the growth of multiple NSCLC lines but not normal human bronchial
      epithelial cell (HBEC) lines. Silencing of DHHC5 by lentivirus-mediated
      expression of DHHC5 shRNAs dramatically reduced in vitro cell proliferation,
      colony formation, and cell invasion in a subset of cell lines that were examined
      in further detail. The phenotypes were restored by transfection of a wild-type
      DHHC5 plasmid but not by a plasmid expressing a catalytically inactive DHHC5.
      Tumor xenograft formation was severely inhibited by DHHC5 knockdown and rescued
      by DHHC5 expression, using both a conventional and tetracycline-inducible shRNA.
      These data indicate that DHHC5 has oncogenic capacity and contributes to tumor
      formation in NSCLC, thus representing a potential novel therapeutic target.
      IMPLICATIONS: Inhibitors of DHHC5 enzyme activity may inhibit non-small cell lung
      cancer growth.

PMID- 25573955
TI  - Coronary calcification among 3477 asymptomatic and symptomatic individuals.
AB  - BACKGROUND: Coronary artery calcification (CAC) can be detected by cardiac
      computed tomography (CT), is associated to cardiovascular risk, and common in
      asymptomatic individuals and patients referred for cardiac CT. DESIGN: CAC was
      evaluated in asymptomatic individuals and symptomatic patients referred for
      cardiac CT, to assess whether differences in CAC may be explained by symptoms or
      traditional cardiovascular risk factors. METHODS: The presence and extent of CAC,
      gender, family history of coronary artery disease, hypertension, hyperlipidaemia,
      diabetes and tobacco were compared in 1220 asymptomatic individuals aged 49-61
      years and 2257 age-matched symptomatic patients referred for cardiac CT with
      suspected coronary artery disease. RESULTS: Symptomatic individuals had a higher
      frequency of a family history of coronary artery disease (46% vs. 23%, p <
      0.001), hypertension (38% vs. 21%, p < 0.001), hyperlipidaemia (42% vs. 12%, p <
      0.001), a trend for more diabetes (6% vs. 5%, p = 0.05), but no significant
      difference was observed for the presence of CAC (Agatston > 0; 45% vs. 45%, p =
      0.94) or severe calcifications (Agatston > 400; 6% vs. 5%, p = 0.36). In
      multivariate analyses age (odds ratio (OR) 1.09-1.18), male gender (OR 3.5-6.43),
      hypertension (OR 1.42-1.79), hyperlipidaemia (OR 1.86-2.09) and tobacco use (OR
      1.83-2.01) were predictors for the presence and extent of CAC, whereas symptoms
      were not predictive for the presence of (Agatston > 0, OR 0.70 (0.59-0.83)), mild
      (Agatston >= 10; OR 0.85 (0.71-1.02)), moderate (Agatston >= 100; OR 0.99 (0.79
      1.24)) or severe calcifications (Agatston >= 400; OR 0.93 (0.65-1.33)).
      CONCLUSION: No difference in the presence or severity of coronary calcifications
      was observed between asymptomatic and symptomatic middle-aged individuals. After
      adjusting for cardiovascular risk factors, symptoms were not predictive for the
      presence or extent of CAC.

PMID- 25573954
TI  - Differential Effects of Tyrosine Kinase Inhibitors on Normal and Oncogenic EGFR
      Signaling and Downstream Effectors.
AB  - Constitutive activation of EGFR due to overexpression or mutation in tumor cells
      leads to dysregulated downstream cellular signaling pathways. Therefore, EGFR as
      well as its downstream effectors have been identified as important therapeutic
      targets. The FDA-approved small-molecule inhibitors of EGFR, gefitinib (Iressa)
      and erlotinib (Tarceva), are clinically effective in a subset of patients with
      non-small cell lung cancer (NSCLC) whose tumors harbor activating mutations
      within the kinase domain of EGFR. The current study examined effects of these
      drugs in 32D cells expressing native (WT) or oncogenic (L858R) EGFR as well as in
      cancer cell lines A431 and H3255. Distinct patterns for gefitinib and erlotinib
      inhibition of EGFR autophosphorylation at individual tyrosines were revealed for
      wild-type (WT) and L858R EGFR. Phosphorylation of Y845 has been shown to be
      important in cancer cells and Y1045 phosphorylation is linked to Cbl-mediated
      ubiquitination and degradation. Dramatic differences were observed by greater
      potency of these drugs for inhibiting downstream effectors for L858R EGFR
      including Cbl and STAT5. Selective targeting of Cbl may play a role in oncogene
      addiction and effects on STAT5 identify features of signaling circuitry for L858R
      EGFR that contribute to drug sensitivity and clinical efficacy. These data
      provide new understanding of the EGFR signaling environment and suggest useful
      paradigms for predicting patient response to EGFR-targeted therapy as well as
      combination treatments. IMPLICATIONS: This study offers fundamental insights for
      understanding molecular mechanisms of drug sensitivity on oncogenic forms of EGFR
      and downstream signaling components as well as considerations for further drug
      optimization and design of combination therapy.

PMID- 25573956
TI  - Inhibition of p70S6K1 Activation by Pdcd4 Overcomes the Resistance to an IGF
      1R/IR Inhibitor in Colon Carcinoma Cells.
AB  - Agents targeting insulin-like growth factor 1 receptor (IGF-1R) are being
      actively examined in clinical trials. Although there has been some initial
      success of single-agent targeting IGF-1R, attempts in later studies failed
      because of resistance. This study aimed to understand the effects of programmed
      cell death 4 (Pdcd4) on the chemosensitivity of the IGF-1R inhibitor OSI-906 in
      colorectal cancer cells and the mechanism underlying this impact. Using OSI-906
      resistant and -sensitive colorectal cancer cells, we found that the Pdcd4 level
      directly correlates with cell chemosensitivity to OSI-906. In addition, tumors
      derived from Pdcd4 knockdown cells resist the growth inhibitory effect of OSI-906
      in a colorectal cancer xenograft mouse model. Moreover, Pdcd4 enhances the
      antiproliferative effect of OSI-906 in resistant cells through suppression of
      p70S6K1 activation. Knockdown of p70S6K1, but not p70S6K2, significantly
      increases the chemosensitivity of OSI-906 in cultured colorectal cancer cells.
      Furthermore, the combination of OSI-906 and PF-4708671, a p70S6K1 inhibitor,
      efficiently suppresses the growth of OSI-906-resistant colon tumor cells in vitro
      and in vivo. Taken together, activation of p70S6K1 that is inhibited by Pdcd4 is
      essential for resistance to the IGF-1R inhibitor in colon tumor cells, and the
      combinational treatment of OSI-906 and PF-4708671 results in enhanced
      antiproliferation effects in colorectal cancer cells in vitro and in vivo,
      providing a novel venue to overcome the resistance to the IGF-1R inhibitor in
      treating colorectal cancer.

PMID- 25573957
TI  - Early discontinuation and related treatment costs after initiation of Basal
      insulin in type 2 diabetes patients: a German primary care database analysis.
AB  - AIMS: The aim was to compare early discontinuation and related treatment costs in
      type 2 diabetes in primary care after initiation of insulin glargine or human
      basal insulin (NPH). METHODS: Overall, 2765 glargine and 1554 NPH patients from
      1072 general practices were analyzed (Disease Analyser). Early discontinuation
      was defined as switching to a different basal insulin or another insulin
      treatment regimen within 90 days after first basal insulin prescription (index
      date, ID). Treatment costs were assessed 365 days prior and post ID in both
      groups. Propensity score matching and linear regression was used to adjust cost
      differences (post vs prior ID: discontinued vs continued patients) for age, sex,
      diabetes duration, antidiabetic comedication, diabetologist care, disease
      management program participation, costs before ID, and Charlson Comorbidity
      Index. RESULTS: Within 3 months after ID, 13% of glargine patients switched to
      other insulin treatment regimens (NPH: 18%; P < .05). After propensity score
      matching, adjusted cost differences in 146 discontinued versus 1342 continued
      glargine patients were calculated (NPH: 146 vs 1342). Diabetes-related
      prescription costs were lower among persistent glargine patients compared to
      persistent NPH patients (EUR-49 [19]; P = .0109). Mean cost difference for
      diabetes-related prescriptions was lower among those who persisted on glargine
      compared to those who switched to other treatment regimens (EUR-74 [42], P =
      .0780). CONCLUSIONS: Treatment persistence within 3 months after basal insulin
      initiation was significantly higher under insulin glargine compared to NPH.
      Diabetes-related prescription costs were significantly lower among patients who
      adhered to insulin glargine compared to persistent NPH patients.

PMID- 25573958
TI  - Terminal-repeat retrotransposons with GAG domain in plant genomes: a new
      testimony on the complex world of transposable elements.
AB  - A novel structure of nonautonomous long terminal repeat (LTR) retrotransposons
      called terminal repeat with GAG domain (TR-GAG) has been described in plants,
      both in monocotyledonous, dicotyledonous and basal angiosperm genomes. TR-GAGs
      are relatively short elements in length (<4 kb) showing the typical features of
      LTR-retrotransposons. However, they carry only one open reading frame coding for
      the GAG precursor protein involved for instance in transposition, the assembly,
      and the packaging of the element into the virus-like particle. GAG precursors
      show similarities with both Copia and Gypsy GAG proteins, suggesting evolutionary
      relationships of TR-GAG elements with both families. Despite the lack of the
      enzymatic machinery required for their mobility, strong evidences suggest that TR
      GAGs are still active. TR-GAGs represent ubiquitous nonautonomous structures that
      could be involved in the molecular diversities of plant genomes. 

PMID- 25573959
TI  - Inference of distant genetic relations in humans using "1000 genomes".
AB  - Nucleotide sequence differences on the whole-genome scale have been computed for
      1,092 people from 14 populations publicly available by the 1000 Genomes Project.
      Total number of differences in genetic variants between 96,464 human pairs has
      been calculated. The distributions of these differences for individuals within
      European, Asian, or African origin were characterized by narrow unimodal peaks
      with mean values of 3.8, 3.5, and 5.1 million, respectively, and standard
      deviations of 0.1-0.03 million. The total numbers of genomic differences between
      pairs of all known relatives were found to be significantly lower than their
      respective population means and in reverse proportion to the distance of their
      consanguinity. By counting the total number of genomic differences it is possible
      to infer familial relations for people that share down to 6% of common loci
      identical-by-descent. Detection of familial relations can be radically improved
      when only very rare genetic variants are taken into account. Counting of total
      number of shared very rare single nucleotide polymorphisms (SNPs) from whole
      genome sequences allows establishing distant familial relations for persons with
      eighth and ninth degrees of relationship. Using this analysis we predicted 271
      distant familial pairwise relations among 1,092 individuals that have not been
      declared by 1000 Genomes Project. Particularly, among 89 British and 97 Chinese
      individuals we found three British-Chinese pairs with distant genetic
      relationships. Individuals from these pairs share identical-by-descent DNA
      fragments that represent 0.001%, 0.004%, and 0.01% of their genomes. With
      affordable whole-genome sequencing techniques, very rare SNPs should become
      important genetic markers for familial relationships and population
      stratification. 

PMID- 25573960
TI  - Studying genome heterogeneity within the arbuscular mycorrhizal fungal cytoplasm.
AB  - Although heterokaryons have been reported in nature, multicellular organisms are
      generally assumed genetically homogeneous. Here, we investigate the case of
      arbuscular mycorrhizal fungi (AMF) that form symbiosis with plant roots. The
      growth advantages they confer to their hosts are of great potential benefit to
      sustainable agricultural practices. However, measuring genetic diversity for
      these coenocytes is a major challenge: Within the same cytoplasm, AMF contain
      thousands of nuclei and show extremely high levels of genetic variation for some
      loci. The extent and physical location of polymorphism within and between AMF
      genomes is unclear. We used two complementary strategies to estimate genetic
      diversity in AMF, investigating polymorphism both on a genome scale and in
      putative single copy loci. First, we used data from whole-genome pyrosequencing
      of four AMF isolates to describe genetic diversity, based on a conservative
      network-based clustering approach. AMF isolates showed marked differences in
      genome-wide diversity patterns in comparison to a panel of control fungal
      genomes. This clustering approach further allowed us to provide conservative
      estimates of Rhizophagus spp. genomes sizes. Second, we designed new putative
      single copy genomic markers, which we investigated by massive parallel amplicon
      sequencing for two Rhizophagus irregularis and one Rhizophagus sp. isolates. Most
      loci showed high polymorphism, with up to 103 alleles per marker. This
      polymorphism could be distributed within or between nuclei. However, we argue
      that the Rhizophagus isolates under study might be heterokaryotic, at least for
      the putative single copy markers we studied. Considering that genetic information
      is the main resource for identification of AMF, we suggest that special attention
      is warranted for the study of these ecologically important organisms.

PMID- 25573961
TI  - The association between vascular endothelial growth factor (VEGF) +405G>C genetic
      polymorphism and endometriosis.
AB  - The vascular endothelial growth factor (VEGF) is one of the most important
      candidate genes for the development of endometriosis, and VEGF genetic
      polymorphisms might be potentially associated with endometriosis risk. However,
      the results still remain controversial. The objective of this study aimed to
      perform a comprehensive meta-analysis to explore a better understanding of the
      effects of VEGF +405G>C genetic polymorphism on the risk of endometriosis. A
      total of eleven eligible studies were eventually identified in this meta
      analysis, including 2829 endometriosis cases and 2947 controls. In the overall
      analysis, no significant association between the VEGF +405G>C genetic
      polymorphism and the risk of endometriosis was detected in all genetic models
      (for homozygote comparison [CC versus vs. GG]: OR = 1.21, 95% CI 0.67-2.19, P =
      0.537; for heterozygote comparison [CG vs. GG]: OR = 1.16, 95% CI 0.86-1.56, P =
      0.348; for dominant comparison CC/CG vs. GG: OR = 1.10, 95% CI 0.93-1.30, P =
      0.263; for recessive comparison [CC vs. CG/GG]: OR = 1.03, 95% CI 0.73-1.47, P =
      0.857; allele comparison [C vs. G]: OR = 0.99, 95% CI 0.70-1.40, P = 0.962). In
      the subgroup analysis by ethnicities, there was no significant association
      between VEGF +405G>C genetic polymorphism and endometriosis risk in Asians and/or
      Caucasians under all genetic models (all P-values >0.05). No publication bias was
      observed in this study. This meta-analysis supports that the VEGF +405G>C genetic
      polymorphism is not significant associated with the risk of endometriosis.

PMID- 25573963
TI  - The role of RIAM in platelets put to a test.
AB  - In this issue of Blood, Stritt et al show that platelet functions dependent on
      integrin activation are unimpaired in mice lacking the Rap1-GTP-interacting
      adaptor molecule (RIAM).

PMID- 25573962
TI  - Complement component 1, q subcomponent binding protein is a marker for
      proliferation in breast cancer.
AB  - Complement component 1, q subcomponent binding protein (C1QBP), is a multi
      compartmental protein with higher mRNA expression reported in breast cancer
      tissues. This study evaluated the association between immunohistochemical
      expression of the C1QBP protein in breast cancer tissue microarrays (TMAs) and
      clinicopathological parameters, in particular tumor size. In addition, an in
      vitro study was conducted to substantiate the breast cancer TMA findings. Breast
      cancer TMAs were constructed from pathological specimens of patients diagnosed
      with invasive ductal carcinoma. C1QBP protein and proliferating cell nuclear
      antigen (PCNA) immunohistochemical analyses were subsequently performed in the
      TMAs. C1QBP immunostaining was detected in 131 out of 132 samples examined. The
      C1QBP protein was predominantly localized in the cytoplasm of the breast cancer
      cells. Univariate analysis revealed that a higher C1QBP protein expression was
      significantly associated with older patients (P = 0.001) and increased tumor size
      (P = 0.002). Multivariate analysis showed that C1QBP is an independent predictor
      of tumor size in progesterone-positive tumors. Furthermore, C1QBP was also
      significantly correlated with expression of PCNA, a known marker of
      proliferation. Inhibition of C1QBP expression was performed by transfecting C1QBP
      siRNA into T47D breast cancer cells, a progesterone receptor-positive breast
      cancer cell line. C1QBP gene expression was analyzed by real-time RT-PCR, and
      protein expression by Western blot. Cell proliferation assays were also performed
      by commercially available assays. Down-regulation of C1QBP expression
      significantly decreased cell proliferation and growth in T47D cells. Taken
      together, our findings suggest that the C1QBP protein could be a potential
      proliferative marker in breast cancer. 

PMID- 25573964
TI  - Superficial venous thrombosis: deeper than meets the eye?
AB  - In this issue of Blood, Cannegieter et al use the Danish National Patient
      Registry to report on the high incidence of venous thromboembolism (VTE),
      mortality, and arterial thrombosis following a diagnosis of superficial vein
      thrombosis (SVT).

PMID- 25573965
TI  - Yin and yang of glucocorticoid receptors in apoptosis.
AB  - In this issue of Blood, Jing et al have identified 2 novel pathways involved in
      the dexamethasone response in pediatric B-precursor acute lymphoblastic leukemia
      (ALL).

PMID- 25573966
TI  - Novel target to kill CLL.
AB  - In this issue of Blood, Liu et al report on OSU-T315, a new agent that
      specifically disrupts the phosphatidylinositol 3-kinase (PI3K)/protein kinase B
      (AKT) pathway and shows high proapoptotic activity against chronic lymphocytic
      leukemia (CLL) cells, which may indicate a potential therapeutic application in
      this disease

PMID- 25573967
TI  - TET2 loss, a rescue of JAK2V617F HSCs.
AB  - In this issue of Blood, Chen et al and Kameda et al demonstrate that Tet2 loss
      has 2 effects in Jak2V617F mice: it increases both the severity of the
      myeloproliferative disorders and the self-renewal properties of the Jak2V617F
      hematopoietic stem cells (HSCs).

PMID- 25573968
TI  - Basophils take a slice of IRF8 pie.
AB  - In this issue of Blood, Sasaki and colleagues demonstrate a strict requirement
      for the transcription factor interferon regulator factor 8 (IRF8) in the
      development of mouse basophils.

PMID- 25573969
TI  - A lymphocyte-mediated cause of secondary PAP.
AB  - In this issue of Blood, Iriguchi et al report that T-lymphocyte-restricted
      overexpression of T-bet causes a maturational arrest in mononuclear phagocyte
      lineage cells and severe secondary pulmonary alveolar proteinosis (PAP).

PMID- 25573970
TI  - Malaria selectively targets pregnancy receptors.
AB  - In this issue of Blood, Rieger et al show that malaria parasite infiltration in
      the human placenta requires a specific geometry and affinity of host receptors to
      facilitate strong adhesion.

PMID- 25573971
TI  - Proteasome inhibitor carfilzomib complements ibrutinib's action in chronic
      lymphocytic leukemia.

PMID- 25573972
TI  - Future distribution of multiple myeloma in the United States by sex, age, and
      race/ethnicity.

PMID- 25573973
TI  - First characterization of platelet secretion defect in patients with familial
      hemophagocytic lymphohistiocytosis type 3 (FHL-3).

PMID- 25573974
TI  - Complications in children and adolescents with Chuvash polycythemia.

PMID- 25573975
TI  - Higher-than-expected prevalence of silent cerebral infarcts in children with
      hemoglobin SC disease.

PMID- 25573976
TI  - HLA-matched related-donor HSCT in Fanconi anemia patients conditioned with
      cyclophosphamide and fludarabine.

PMID- 25573977
TI  - Infections of diabetic foot ulcers with methicillin-resistant Staphylococcus
      aureus.
AB  - Infected diabetic foot is the most common reason for hospitalization and
      complications in patients with type 2 diabetes mellitus (DM2). Methicillin
      resistant Staphylococcus aureus (MRSA) is frequently isolated from such lesions,
      and its presence is growing, seriously deteriorating the infected patient's
      quality of life. The aim of this study was to assess the prevalence of MRSA as
      well as other microbiota in 100 patients diagnosed with (DM2) and with infected
      foot ulcers at the Hospital General de Mexico. The main results obtained show a
      prevalence of Staphylococcus aureus (42%), followed by Escherichia coli (36%)
      and, in lower percentages, other bacteria. MRSA was predominant (34%), and we
      conclude that the use of cefoxitin instead of oxacillin as the first-choice
      antibiotic has an advantage because it is a better inducer of methicillin
      resistance expression. 

PMID- 25573979
TI  - Successful Surgical Treatment for Elephantiasis Nostras Verrucosa Using a New
      Designed Column Flap.
AB  - Elephantiasis nostras verrucosa is a chronic lymphedema that causes enlarged and
      disfigured extremities. There are plenty of treatment options. However, there is
      no complete treatment. Preventive or symptomatic therapy is the basis for
      treating elephantiasis. In this article, we report a case of elephantiasis
      nostras verrucosa treated successfully by surgical reconstruction using a newly
      designed column flap. 

PMID- 25573978
TI  - Epidemiology of type 2 diabetic foot problems and predictive factors for
      amputation in China.
AB  - To determine incidence and clinically relevant risk factors for diabetic
      amputation in a large cohort study of diabetic foot ulceration patients in China,
      we investigated a total of 669 diabetic foot ulceration patients, who were
      assessed at baseline for demographic information, medical and social history,
      peripheral neuropathy screening, periphery artery disease screening, assessment
      of nutritional status and diabetic control, physical examination including foot
      deformity in 15 Grade III-A hospitals. Of the 669 patients, 435 were male and 201
      were female, with the mean age being 64.0 years. Of all patients, 110 had
      neuropathic ulcers, 122 had ischemic ulcers, 276 had neuroischemic ulcers, and 12
      cases were unclassified. Wagner classification showed 61 cases were grade I, 216
      cases grade II, 159 cases grade III, 137 cases grade IV, and 7 cases grade V. The
      overall amputation rate among diabetic foot patients was 19.03%, and major and
      minor amputation rates were 2.14% and 16.88%, respectively. By univariate
      analysis, statistically significant differences were found in smoking, rest pain,
      ulcer history, revascularization history, amputation history, gangrene,
      infection, Wagner grades, duration of diabetes, and postprandial blood glucose,
      aldehyde, total protein, globulin, albumin, white blood cell (WBC), hemoglobin,
      HbA1c, ulcer property, body mass index, as well as creatinine. Binary logistic
      regression model showed that increased WBC (odds ratio 1.25) and ulcer history
      (odds ratio 6.8) were associated with increased risks from diabetic foot ulcer to
      major amputation; increased duration of diabetes (odds ratio 1.004), WBC (odds
      ratio 1.102), infection (odds ratio 2.323), foot deformity (odds ratio 1.973),
      revascularization history (odds ratio 2.662), and decreased postprandial blood
      sugar (odds ratio 0.94) were associated with increased risks from diabetic foot
      ulcer to minor amputation. It is of great importance to give better management to
      diabetic patients at early stages. Following a diagnosis of DFU more intensive
      surveillance and aggressive care may improve outcome. 

PMID- 25573983
TI  - Anticoagulation during pregnancy in women with prosthetic valves: evidence,
      guidelines and unanswered questions.
AB  - The management of women with mechanical heart valves during pregnancy remains
      difficult and controversial. There is no ideal anticoagulation regimen for this
      unique population, as there are inherent risks and benefits of each approach for
      both mother and fetus. There has been limited data available to guide the
      clinician in the optimal treatment strategy for an individual patient. The
      AHA/ACC Guidelines for the Management of Patients with Valvular Heart Disease
      created class recommendations for this population based upon current evidence,
      which is summarized in this review. 

PMID- 25573985
TI  - Ventricular tachycardia following aortic valve replacement.

PMID- 25573984
TI  - Two-year clinical outcome from the Iberian registry patients after left atrial
      appendage closure.
AB  - AIMS: The aim of this study was to observe the percentage of thromboembolic and
      haemorrhagic events over a 2-year follow-up in patients with non-valvular atrial
      fibrillation (NVAF) undergoing closure of the left atrial appendage (LAA) with an
      occlusion device. Observed events and CHADS2 (congestive heart failure,
      hypertension, age, diabetes, stroke history), CHA2DS2-VASc (also adding: vascular
      disease and sex) and HAS-BLED (hypertension, abnormal liver/renal function,
      stroke history, bleeding predisposition, labile international normalised ratios,
      elderly, drugs/alcohol use)-predicted events were compared. METHODS: LAA closure
      with an occlusion device was performed in 167 NVAF patients contraindicated for
      oral anticoagulants and recruited from 12 hospitals between 2009 and 2013. At
      least two transoesophageal echocardiograms were performed in the first 6 months
      postimplantation. Antithrombotics included clopidogrel and aspirin. Patients were
      monitored for death, stroke, major and relevant bleeding and hospitalisation for
      concomitant conditions. Mean age was 74.68+/-8.58, median follow-up was 24
      months, 5.38% had intraoperative complications and implantation was successful in
      94.6% of subjects. Mortality during follow-up was 10.8%, mostly (9.5%) non
      cardiac related. Bleeding occurred in 10.1% of subjects, 5.7% major and 4.4%
      minor though relevant, and 4.4% suffered stroke. Major bleeding and
      stroke/transient ischaemic attack events within 2 years (annual event rates, 290
      patients/year) were less frequent than expected from CHADS2 (2.4% vs 9.6%),
      CHA2DS2-VASc (2.4% vs 8.3%) and HAS-BLED (3.1% vs 6.6%) risk scores (p<0.001,
      p=0.003, p=0.047, respectively). CONCLUSIONS: LAA closure with an occlusion
      device in patients contraindicated for oral anticoagulants is a therapeutic
      option associated with fewer thromboembolic and haemorrhagic events than expected
      from risk scores, particularly in the second year postimplantation.

PMID- 25573986
TI  - A unique population of IgG-expressing plasma cells lacking CD19 is enriched in
      human bone marrow.
AB  - Specific serum antibodies mediating humoral immunity and autoimmunity are
      provided by mature plasma cells (PC) residing in the bone marrow (BM), yet their
      dynamics and composition are largely unclear. We here characterize distinct
      subsets of human PC differing by CD19 expression. Unlike CD19(+) PC, CD19(-) PC
      were restricted to BM, expressed predominantly IgG, and they carried a
      prosurvival, distinctly mature phenotype, that is, HLA-DR(low)Ki-67(
      )CD95(low)CD28(+)CD56(+/-), with increased BCL2 and they resisted their
      mobilization from the BM after systemic vaccination. Fewer mutations within
      immunoglobulin VH rearrangements of CD19(-) BMPC may indicate their
      differentiation in early life. Their resistance to in vivo B-cell depletion, that
      is, their independency from supply with new plasmablasts, is consistent with long
      term stability of this PC subset in the BM. Moreover, CD19(-) PC were detectable
      in chronically inflamed tissues and secreted autoantibodies. We propose a
      multilayer model of PC memory in which CD19(+) and CD19(-) PC represent dynamic
      and static components, respectively, permitting both adaptation and stability of
      humoral immune protection. 

PMID- 25573987
TI  - Brentuximab vedotin demonstrates objective responses in a phase 2 study of
      relapsed/refractory DLBCL with variable CD30 expression.
AB  - Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell
      lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated
      the efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in
      relapsed/refractory CD30(+) NHL. This planned subset analysis of B-cell NHLs
      includes 49 patients with DLBCL and 19 with other B-cell NHLs. Objective response
      rate was 44% for DLBCL, including 8 (17%) complete remissions (CRs) with a median
      duration of 16.6 months thus far (range, 2.7 to 22.7+ months). There was no
      statistical correlation between response and level of CD30 expression; however,
      all responding patients had quantifiable CD30 by computer-assisted assessment of
      immunohistochemistry. DLBCL patients were generally refractory to first-line
      (76%) and most recent therapies (82%), and 44% of these refractory patients
      responded (15% CRs). Patients with other B-cell lymphomas also responded: 1 CR, 2
      partial responses (PRs) of 6 with gray zone, 1 CR of 6 with primary mediastinal B
      cell, and 1 CR of 3 with posttransplant lymphoproliferative disorder. Adverse
      events were consistent with known toxicities. The combination of brentuximab
      vedotin with rituximab was generally well tolerated and had activity similar to
      brentuximab vedotin alone. Overall, significant activity with brentuximab vedotin
      was observed in relapsed/refractory DLBCL, and responses occurred across a range
      of CD30 expression. This study was registered at www.clinicaltrials.gov as
      #NCT01421667. 

PMID- 25573988
TI  - Colony stimulating factor-1 receptor signaling networks inhibit mouse macrophage
      inflammatory responses by induction of microRNA-21.
AB  - Macrophage polarization between the M2 (repair, protumorigenic) and M1
      (inflammatory) phenotypes is seen as a continuum of states. The detailed
      transcriptional events and signals downstream of colony-stimulating factor 1
      receptor (CSF-1R) that contributes to amplification of the M2 phenotype and
      suppression of the M1 phenotype are largely unknown. Macrophage CSF-1R pTyr-721
      signaling promotes cell motility and enhancement of tumor cell invasion in vitro.
      Combining analysis of cellular systems for CSF-1R gain of function and loss of
      function with bioinformatic analysis of the macrophage CSF-1R pTyr-721-regulated
      transcriptome, we uncovered microRNA-21 (miR-21) as a downstream molecular switch
      controlling macrophage activation and identified extracellular signal-regulated
      kinase1/2 and nuclear factor-kappaB as CSF-1R pTyr-721-regulated signaling nodes.
      We show that CSF-1R pTyr-721 signaling suppresses the inflammatory phenotype,
      predominantly by induction of miR-21. Profiling of the miR-21-regulated messenger
      RNAs revealed that 80% of the CSF-1-regulated canonical miR-21 targets are
      proinflammatory molecules. Additionally, miR-21 positively regulates M2 marker
      expression. Moreover, miR-21 feeds back to positively regulate its own expression
      and to limit CSF-1R-mediated activation of extracellular signal-regulated
      kinase1/2 and nuclear factor-kappaB. Consistent with an anti-inflammatory role of
      miRNA-21, intraperitoneal injection of mice with a miRNA-21 inhibitor increases
      the recruitment of inflammatory monocytes and enhances the peritoneal
      monocyte/macrophage response to lipopolysaccharide. These results identify the
      CSF-1R-regulated miR-21 network that modulates macrophage polarization. 

PMID- 25573990
TI  - HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human
      aggressive B-cell non-Hodgkin lymphoma.
AB  - We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock
      protein (HSP)H1/105 in function of their aggressiveness. Here, we now clarify its
      role as a functional B-NHL target by testing the hypothesis that it promotes the
      stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of
      aggressive B-NHLs was paralleled by Bcl-6 and c-Myc downregulation. In vitro and
      in vivo analysis of HSPH1-silenced Namalwa cells showed that this effect was
      associated with a significant growth delay and the loss of tumorigenicity when
      10(4) cells were injected into mice. Interestingly, we found that HSPH1
      physically interacts with c-Myc and Bcl-6 in both Namalwa cells and primary
      aggressive B-NHLs. Accordingly, expression of HSPH1 and either c-Myc or Bcl-6
      positively correlated in these diseases. Our study indicates that HSPH1
      concurrently favors the expression of 2 key lymphoma oncoproteins, thus
      confirming its candidacy as a valuable therapeutic target of aggressive B-NHLs. 

PMID- 25573989
TI  - shRNA library screening identifies nucleocytoplasmic transport as a mediator of
      BCR-ABL1 kinase-independent resistance.
AB  - The mechanisms underlying tyrosine kinase inhibitor (TKI) resistance in chronic
      myeloid leukemia (CML) patients lacking explanatory BCR-ABL1 kinase domain
      mutations are incompletely understood. To identify mechanisms of TKI resistance
      that are independent of BCR-ABL1 kinase activity, we introduced a lentiviral
      short hairpin RNA (shRNA) library targeting ~5000 cell signaling genes into
      K562(R), a CML cell line with BCR-ABL1 kinase-independent TKI resistance
      expressing exclusively native BCR-ABL1. A customized algorithm identified genes
      whose shRNA-mediated knockdown markedly impaired growth of K562(R) cells compared
      with TKI-sensitive controls. Among the top candidates were 2 components of the
      nucleocytoplasmic transport complex, RAN and XPO1 (CRM1). shRNA-mediated RAN
      inhibition or treatment of cells with the XPO1 inhibitor, KPT-330 (Selinexor),
      increased the imatinib sensitivity of CML cell lines with kinase-independent TKI
      resistance. Inhibition of either RAN or XPO1 impaired colony formation of CD34(+)
      cells from newly diagnosed and TKI-resistant CML patients in the presence of
      imatinib, without effects on CD34(+) cells from normal cord blood or from a
      patient harboring the BCR-ABL1(T315I) mutant. These data implicate RAN in BCR
      ABL1 kinase-independent imatinib resistance and show that shRNA library screens
      are useful to identify alternative pathways critical to drug resistance in CML. 

PMID- 25573991
TI  - Outcomes of patients with chronic lymphocytic leukemia after discontinuing
      ibrutinib.
AB  - Ibrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of
      patients with relapsed refractory chronic lymphocytic leukemia (RR-CLL). We
      describe the characteristics, causes of discontinuation, and outcomes in patients
      who discontinued treatment with ibrutinib. One hundred twenty-seven patients were
      enrolled in various clinical trials of ibrutinib, with or without rituximab, at
      our center. Thirty-three (26%) patients have discontinued ibrutinib to date. The
      majority of those patients had high-risk features: 94% with unmutated
      immunoglobulin heavy chain variable gene rearrangement, 58% with del(17p) by
      fluorescence in situ hybridization, and 54% with a complex karyotype. Causes of
      discontinuation were disease transformation (7), progressive CLL (7), stem cell
      transplantation (3), adverse events (11), serious adverse events/deaths (3), and
      miscellaneous reasons (2). Twenty five patients (76%) died after discontinuing
      ibrutinib; the median overall survival was 3.1 months after discontinuation. Most
      patients with RR-CLL who discontinued ibrutinib early were difficult to treat and
      had poor outcomes. 

PMID- 25573993
TI  - Marked hyperferritinemia does not predict for HLH in the adult population.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of uncontrolled
      immune activation that has gained increasing attention during the last decade.
      The diagnosis of HLH is based on a constellation of clinical and laboratory
      abnormalities, including elevated serum ferritin levels. In the pediatric
      population, marked hyperferritinemia is specific for HLH. To determine what
      conditions are associated with profoundly elevated ferritin in the adult
      population, we performed a retrospective analysis in a large academic health care
      system. We identified 113 patients with serum ferritin levels higher than 50,000
      ug/L. The most frequently observed conditions included renal failure,
      hepatocellular injury, infections, and hematologic malignancies. Our results
      suggest that marked hyperferritinemia can be seen in a variety of conditions and
      is not specific for HLH in adults.

PMID- 25573992
TI  - The role of rituximab in the management of patients with acquired thrombotic
      thrombocytopenic purpura.

PMID- 25573995
TI  - Judging synthetic biology risks.

PMID- 25573998
TI  - Intellectual property. U.S. patent office reworks unpopular policy.

PMID- 25573997
TI  - Physics. Laser fusion, with a difference.

PMID- 25573994
TI  - MRTF-SRF signaling is required for seeding of HSC/Ps in bone marrow during
      development.
AB  - Chemokine signaling is important for the seeding of different sites by
      hematopoietic stem cells (HSCs) during development. Serum response factor (SRF)
      controls multiple genes governing adhesion and migration, mainly by recruiting
      members of the myocardin-related transcription factor (MRTF) family of G-actin
      regulated cofactors. We used vav-iCre to inactivate MRTF-SRF signaling early
      during hematopoietic development. In both Srf- and Mrtf-deleted animals,
      hematopoiesis in fetal liver and spleen is intact but does not become established
      in fetal bone marrow. Srf-null HSC progenitor cells (HSC/Ps) fail to effectively
      engraft in transplantation experiments, exhibiting normal proximal signaling
      responses to SDF-1, but reduced adhesiveness, F-actin assembly, and reduced
      motility. Srf-null HSC/Ps fail to polarize in response to SDF-1 and cannot
      migrate through restrictive membrane pores to SDF-1 or Scf in vitro. Mrtf-null
      HSC/Ps were also defective in chemotactic responses to SDF-1. Srf-null HSC/Ps
      exhibit substantial deficits in cytoskeletal gene expression. MRTF-SRF signaling
      is thus critical for expression of genes required for the response to chemokine
      signaling during hematopoietic development. 

PMID- 25574000
TI  - Space science. Air Force turns a keen eye on space junk.

PMID- 25573999
TI  - Bioelectronics. A soft approach kick-starts cybernetic implants.

PMID- 25574002
TI  - Salvaging science.

PMID- 25574001
TI  - Computer science. Beyond the Turing Test.

PMID- 25574003
TI  - On the trail of contagion.

PMID- 25574004
TI  - Computer science. Solving imperfect-information games.

PMID- 25574005
TI  - RNA. Prescribing splicing.

PMID- 25574006
TI  - Biochemistry. Coping with oxidative stress.

PMID- 25574007
TI  - Physics. Dynamics of a cold quantum gas.

PMID- 25574008
TI  - Cell biology. Making sense of amino acid sensing.

PMID- 25574009
TI  - Materials assembly. Designing two-dimensional materials that spring rapidly into
      three-dimensional shapes.

PMID- 25574010
TI  - Materials science. Using all energy in a battery.

PMID- 25574011
TI  - Global food supply. China's aquaculture and the world's wild fisheries.

PMID- 25574012
TI  - Retraction.

PMID- 25574013
TI  - Protecting coffee from intensification.

PMID- 25574014
TI  - Measuring merit: take the risk.

PMID- 25574015
TI  - Moving toward data on soil change.

PMID- 25574016
TI  - Computer science. Heads-up limit hold'em poker is solved.
AB  - Poker is a family of games that exhibit imperfect information, where players do
      not have full knowledge of past events. Whereas many perfect-information games
      have been solved (e.g., Connect Four and checkers), no nontrivial imperfect
      information game played competitively by humans has previously been solved. Here,
      we announce that heads-up limit Texas hold'em is now essentially weakly solved.
      Furthermore, this computation formally proves the common wisdom that the dealer
      in the game holds a substantial advantage. This result was enabled by a new
      algorithm, CFR(+), which is capable of solving extensive-form games orders of
      magnitude larger than previously possible. 

PMID- 25574017
TI  - Batteries. In situ visualization of Li/Ag2VP2O8 batteries revealing rate
      dependent discharge mechanism.
AB  - The functional capacity of a battery is observed to decrease, often quite
      dramatically, as discharge rate demands increase. These capacity losses have been
      attributed to limited ion access and low electrical conductivity, resulting in
      incomplete electrode use. A strategy to improve electronic conductivity is the
      design of bimetallic materials that generate a silver matrix in situ during
      cathode reduction. Ex situ x-ray absorption spectroscopy coupled with in situ
      energy-dispersive x-ray diffraction measurements on intact lithium/silver
      vanadium diphosphate (Li/Ag2VP2O8) electrochemical cells demonstrate that the
      metal center preferentially reduced and its location in the bimetallic cathode
      are rate-dependent, affecting cell impedance. This work illustrates that spatial
      imaging as a function of discharge rate can provide needed insights toward
      improving realizable capacity of bimetallic cathode systems. 

PMID- 25574018
TI  - Materials science. Assembly of micro/nanomaterials into complex, three
      dimensional architectures by compressive buckling.
AB  - Complex three-dimensional (3D) structures in biology (e.g., cytoskeletal webs,
      neural circuits, and vasculature networks) form naturally to provide essential
      functions in even the most basic forms of life. Compelling opportunities exist
      for analogous 3D architectures in human-made devices, but design options are
      constrained by existing capabilities in materials growth and assembly. We report
      routes to previously inaccessible classes of 3D constructs in advanced materials,
      including device-grade silicon. The schemes involve geometric transformation of
      2D micro/nanostructures into extended 3D layouts by compressive buckling.
      Demonstrations include experimental and theoretical studies of more than 40
      representative geometries, from single and multiple helices, toroids, and conical
      spirals to structures that resemble spherical baskets, cuboid cages, starbursts,
      flowers, scaffolds, fences, and frameworks, each with single- and/or multiple
      level configurations. 

PMID- 25574020
TI  - Ultrafast dynamics. Four-dimensional imaging of carrier interface dynamics in p-n
      junctions.
AB  - The dynamics of charge transfer at interfaces are fundamental to the
      understanding of many processes, including light conversion to chemical energy.
      Here, we report imaging of charge carrier excitation, transport, and
      recombination in a silicon p-n junction, where the interface is well defined on
      the nanoscale. The recorded images elucidate the spatiotemporal behavior of
      carrier density after optical excitation. We show that carrier separation in the
      p-n junction extends far beyond the depletion layer, contrary to the expected
      results from the widely accepted drift-diffusion model, and that localization of
      carrier density across the junction takes place for up to tens of nanoseconds,
      depending on the laser fluence. The observations reveal a ballistic-type motion,
      and we provide a model that accounts for the spatiotemporal density localization
      across the junction. 

PMID- 25574019
TI  - Biomaterials. Electronic dura mater for long-term multimodal neural interfaces.
AB  - The mechanical mismatch between soft neural tissues and stiff neural implants
      hinders the long-term performance of implantable neuroprostheses. Here, we
      designed and fabricated soft neural implants with the shape and elasticity of
      dura mater, the protective membrane of the brain and spinal cord. The electronic
      dura mater, which we call e-dura, embeds interconnects, electrodes, and
      chemotrodes that sustain millions of mechanical stretch cycles, electrical
      stimulation pulses, and chemical injections. These integrated modalities enable
      multiple neuroprosthetic applications. The soft implants extracted cortical
      states in freely behaving animals for brain-machine interface and delivered
      electrochemical spinal neuromodulation that restored locomotion after paralyzing
      spinal cord injury. 

PMID- 25574021
TI  - Quantum gases. Critical dynamics of spontaneous symmetry breaking in a
      homogeneous Bose gas.
AB  - Kibble-Zurek theory models the dynamics of spontaneous symmetry breaking, which
      plays an important role in a wide variety of physical contexts, ranging from
      cosmology to superconductors. We explored these dynamics in a homogeneous system
      by thermally quenching an atomic gas with short-range interactions through the
      Bose-Einstein phase transition. Using homodyne matter-wave interferometry to
      measure first-order correlation functions, we verified the central quantitative
      prediction of the Kibble-Zurek theory, namely the homogeneous-system power-law
      scaling of the coherence length with the quench rate. Moreover, we directly
      confirmed its underlying hypothesis, the freezing of the correlation length near
      the transition. Our measurements agree with a beyond-mean-field theory and
      support the expectation that the dynamical critical exponent for this
      universality class is z = 3/2.

PMID- 25574022
TI  - Gut microbiota. Antimicrobial peptide resistance mediates resilience of prominent
      gut commensals during inflammation.
AB  - Resilience to host inflammation and other perturbations is a fundamental property
      of gut microbial communities, yet the underlying mechanisms are not well
      understood. We have found that human gut microbes from all dominant phyla are
      resistant to high levels of inflammation-associated antimicrobial peptides (AMPs)
      and have identified a mechanism for lipopolysaccharide (LPS) modification in the
      phylum Bacteroidetes that increases AMP resistance by four orders of magnitude.
      Bacteroides thetaiotaomicron mutants that fail to remove a single phosphate group
      from their LPS were displaced from the microbiota during inflammation triggered
      by pathogen infection. These findings establish a mechanism that determines the
      stability of prominent members of a healthy microbiota during perturbation. 

PMID- 25574023
TI  - Epidemiology. Opposite effects of anthelmintic treatment on microbial infection
      at individual versus population scales.
AB  - Parasitic worms modulate host immune responses in ways that affect microbial co
      infections. For this reason, anthelmintic therapy may be a potent tool for
      indirectly controlling microbial pathogens. However, the population-level
      consequences of this type of intervention on co-infecting microbes are unknown.
      We evaluated the effects of anthelmintic treatment on bovine tuberculosis (BTB)
      acquisition, mortality after infection, and pathogen fitness in free-ranging
      African buffalo. We found that treatment had no effect on the probability of BTB
      infection, but buffalo survival after infection was ninefold higher among treated
      individuals. These contrasting effects translated into an approximately eightfold
      increase in the reproductive number of BTB for anthelmintic-treated compared with
      untreated buffalo. Our results indicate that anthelmintic treatment can enhance
      the spread of microbial pathogens in some real-world situations. 

PMID- 25574026
TI  - My metamorphosis.

PMID- 25574025
TI  - DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA
      double-strand break repair.
AB  - XRCC4 and XLF are two structurally related proteins that function in DNA double
      strand break (DSB) repair. Here, we identify human PAXX (PAralog of XRCC4 and
      XLF, also called C9orf142) as a new XRCC4 superfamily member and show that its
      crystal structure resembles that of XRCC4. PAXX interacts directly with the DSB
      repair protein Ku and is recruited to DNA-damage sites in cells. Using RNA
      interference and CRISPR-Cas9 to generate PAXX(-/-) cells, we demonstrate that
      PAXX functions with XRCC4 and XLF to mediate DSB repair and cell survival in
      response to DSB-inducing agents. Finally, we reveal that PAXX promotes Ku
      dependent DNA ligation in vitro and assembly of core nonhomologous end-joining
      (NHEJ) factors on damaged chromatin in cells. These findings identify PAXX as a
      new component of the NHEJ machinery. 

PMID- 25574024
TI  - Structural biology. Division of labor in transhydrogenase by alternating proton
      translocation and hydride transfer.
AB  - NADPH/NADP(+) (the reduced form of NADP(+)/nicotinamide adenine dinucleotide
      phosphate) homeostasis is critical for countering oxidative stress in cells.
      Nicotinamide nucleotide transhydrogenase (TH), a membrane enzyme present in both
      bacteria and mitochondria, couples the proton motive force to the generation of
      NADPH. We present the 2.8 A crystal structure of the transmembrane proton channel
      domain of TH from Thermus thermophilus and the 6.9 A crystal structure of the
      entire enzyme (holo-TH). The membrane domain crystallized as a symmetric dimer,
      with each protomer containing a putative proton channel. The holo-TH is a highly
      asymmetric dimer with the NADP(H)-binding domain (dIII) in two different
      orientations. This unusual arrangement suggests a catalytic mechanism in which
      the two copies of dIII alternatively function in proton translocation and hydride
      transfer. 

PMID- 25574028
TI  - Direct interactions of adaptor protein complexes 1 and 2 with the copper
      transporter ATP7A mediate its anterograde and retrograde trafficking.
AB  - ATP7A is a P-type ATPase in which diverse mutations lead to X-linked recessive
      Menkes disease or occipital horn syndrome. Recently, two previously unknown ATP7A
      missense mutations, T994I and P1386S, were shown to cause an isolated distal
      motor neuropathy without clinical or biochemical features of other ATP7A
      disorders. These mutant alleles cause subtle defects in ATP7A intracellular
      trafficking, resulting in preferential plasma membrane localization compared with
      wild-type ATP7A. We reported previously that ATP7A(P1386S) causes unstable
      insertion of the eighth and final transmembrane segment, preventing proper
      position of the carboxyl-terminal tail in a proportion of mutant molecules. Here,
      we utilize this and other naturally occurring and engineered mutant ATP7A alleles
      to identify mechanisms of normal ATP7A trafficking. We show that adaptor protein
      (AP) complexes 1 and 2 physically interact with ATP7A and that binding is
      mediated in part by a carboxyl-terminal di-leucine motif. In contrast to other
      ATP7A missense mutations, ATP7A(P1386S) partially disturbs interactions with both
      APs, leading to abnormal axonal localization in transfected NSC-34 motor neurons
      and altered calcium-signaling following glutamate stimulation. Our results imply
      that AP-1 normally tethers ATP7A at the trans-Golgi network in the
      somatodendritic segments of motor neurons and that alterations affecting the
      ATP7A carboxyl-terminal tail induce release of the copper transporter to the
      axons or axonal membranes. The latter effects are intensified by diminished
      interaction with AP-2, impeding ATP7A retrograde trafficking. Taken together,
      these findings further illuminate the normal molecular mechanisms of ATP7A
      trafficking and suggest a pathophysiological basis for ATP7A-related distal motor
      neuropathy. 

PMID- 25574027
TI  - Htt CAG repeat expansion confers pleiotropic gains of mutant huntingtin function
      in chromatin regulation.
AB  - The CAG repeat expansion in the Huntington's disease gene HTT extends a
      polyglutamine tract in mutant huntingtin that enhances its ability to facilitate
      polycomb repressive complex 2 (PRC2). To gain insight into this dominant gain of
      function, we mapped histone modifications genome-wide across an isogenic panel of
      mouse embryonic stem cell (ESC) and neuronal progenitor cell (NPC) lines,
      comparing the effects of Htt null and different size Htt CAG mutations. We found
      that Htt is required in ESC for the proper deposition of histone H3K27me3 at a
      subset of 'bivalent' loci but in NPC it is needed at 'bivalent' loci for both the
      proper maintenance and the appropriate removal of this mark. In contrast, Htt CAG
      size, though changing histone H3K27me3, is prominently associated with altered
      histone H3K4me3 at 'active' loci. The sets of ESC and NPC genes with altered
      histone marks delineated by the lack of huntingtin or the presence of mutant
      huntingtin, though distinct, are enriched in similar pathways with apoptosis
      specifically highlighted for the CAG mutation. Thus, the manner by which
      huntingtin function facilitates PRC2 may afford mutant huntingtin with multiple
      opportunities to impinge upon the broader machinery that orchestrates
      developmentally appropriate chromatin status. 

PMID- 25574030
TI  - Recurrences and fertility after endometrioma ablation in women with and without
      colorectal endometriosis: a prospective cohort study.
AB  - STUDY QUESTION: What are the recurrence and pregnancy rates in women managed for
      ovarian endometrioma by ablation using plasma energy with and without associated
      surgery for colorectal endometriosis? SUMMARY ANSWER: Concomitant management of
      colorectal endometriosis does not impact either risk of recurrences or
      probability of pregnancy in women managed for endometrioma ablation using plasma
      energy. WHAT IS KNOWN ALREADY: No consensus exists on how best to manage patients
      presenting with ovarian endometriomas and colorectal endometriosis, in terms of
      impact on fertility preservation and recurrence rates. STUDY DESIGN, SIZE,
      DURATION: A prospective series of consecutive patients managed for ovarian
      endometriomas by ablation using plasma energy, over a period of 48 consecutive
      months. The study included patients with associated colorectal endometriosis (n =
      52) and those who were free of colorectal localizations of the disease (n = 72).
      No women were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: The
      124 women included in this study were managed for either unilateral or bilateral
      ovarian endometriomas using plasma energy at a university tertiary care center.
      Recurrences and pregnancy rate were compared in patients with and without
      colorectal endometriosis. The minimum length of follow-up was 1 year. Cyst
      recurrences were assessed using pelvic ultrasound and magnetic resonance imaging.
      Kaplan-Meier and actuarial life-table analysis were used to estimate the
      recurrence-free survival curve and the probability of pregnancy. The Cox model
      was used to assess independent predictive factors for recurrences. Pregnancy
      likelihood and independent predictors were estimated using a regression logistic
      model. MAIN RESULTS AND THE ROLE OF CHANCE: Mean follow-up was 32 +/- 18 months.
      Forty-eight patients (40.3%) were presumed infertile and attended an assisted
      reproductive techniques (ART) center. Eighteen patients presented with a
      recurrence (14.5%). Bilateral localization of endometriomas was the only factor
      independently related to an increased risk of recurrences [hazard ratio 3.3, 95%
      confidence interval (CI) 1.2-9.4]. Of the 83 women wishing to conceive (66.9%),
      51 became pregnant (61.4%) and 33 of these pregnancies were spontaneous (64.7%).
      The rates of pregnancy were 65.8% for the group of patients with associated
      colorectal endometriosis and 57.8% for controls (P = 0.50). Age over 35 years was
      the only independent factor for which association with pregnancy rates approached
      the significance threshold (adjusted odds ratio 0.35, 95% CI 0.12-1, P = 0.06).
      LIMITATIONS, REASONS FOR CAUTION: The study sample size may be insufficient to
      reveal statistically significant differences related to risk factors which have
      low impact on the probability of recurrence and pregnancy. Data on ovarian
      reserve before and after the procedure was not available in all patients, which
      would have added to our results and the discussion about treatment of
      endometrioma in general. WIDER IMPLICATIONS OF THE FINDINGS: Concomitant
      management of colorectal endometriosis does not impact either risk of recurrences
      or the probability of pregnancy in women having benefited from ovarian
      endometrioma ablation using plasma energy. Moreover, surgical management of
      colorectal and ovarian endometriosis may allow spontaneous conception in one out
      of three patients, thus reducing expenses related to ART management. STUDY
      FUNDING/COMPETING INTERESTS: No financial support was received for this study.
      Horace Roman reports personal fees for participating in a symposium and
      masterclass presenting his experience in the use of PlasmaJet.

PMID- 25574031
TI  - Does the type of culture medium used influence birthweight of children born after
      IVF?
AB  - STUDY QUESTION: Do culture media influence birthweight of children born after
      IVF? SUMMARY ANSWER: Some studies have observed a significant effect of culture
      media on birthweight, while others have not, but since most studies compared
      different culture media, conventional meta-analysis was not possible. WHAT IS
      KNOWN ALREADY: Animal studies suggest that in vitro culture of embryos can have a
      significant effect on the birthweight of offspring when compared with in vivo
      developed embryos. The type of culture medium (or certain components of the
      medium) used is one of the causal factors. STUDY DESIGN, SIZE, DURATION: We
      reviewed all available literature reporting on a relation between culture medium
      and birthweight in human studies and a selection of animal studies.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: An extensive literature search on
      Pubmed and Medline was performed with relevant search criteria relating to IVF,
      birthweight and culture medium. MAIN RESULTS AND THE ROLE OF CHANCE: Eleven
      studies reporting on a relationship between culture medium and birthweight in
      human were included in this review. Five of these found significant differences
      in birthweight when offspring born after culture in different culture media were
      compared. The remaining studies did not find differences in birthweight after
      changing culture medium. LIMITATIONS, REASONS FOR CAUTION: The number of human
      studies is limited and different culture media with different compositions are
      compared which makes a comparison between the studies difficult, if not
      impossible. Furthermore, most study designs were retrospective with consecutive
      use of different culture media and limited sample sizes, which makes bias of the
      results likely. WIDER IMPLICATIONS OF THE FINDINGS: If it could be confirmed that
      the type of culture medium used does indeed influence phenotypic characteristics
      (such as birthweight) of children born after IVF, it would underline the
      importance of monitoring the health of IVF children in relation to aspects of the
      laboratory techniques used during embryo culture. STUDY FUNDING/COMPETING
      INTERESTS: No funding was applicable to this study. No conflict of interest is
      declared.

PMID- 25574032
TI  - Genome-wide association study identified new susceptibility loci for polycystic
      ovary syndrome.
AB  - STUDY QUESTION: Are there any novel genetic markers of susceptibility to
      polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: We identified a novel
      susceptibility locus on chromosome 8q24.2 and several moderately associated loci
      for PCOS in Korean women. WHAT IS KNOWN ALREADY: PCOS is a highly complex
      disorder with significant contributions from both genetic and environmental
      factors. Previous genome-wide association studies (GWAS) in the Han Chinese
      population identified several risk loci for PCOS. However, GWAS studies on PCOS
      remain very few. The aim of this study was to identify novel markers of
      susceptibility to PCOS through GWAS. STUDY DESIGN, SIZE, DURATION: A two-stage
      GWAS was conducted. The initial discovery set for GWAS consisted of 976 PCOS
      cases and 946 controls. The second stage (replication study) included 249 PCOS
      cases and 778 controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were
      diagnosed according to the Rotterdam criteria. Genomic DNAs were genotyped using
      the HumanOmni1-Quad v1 array. In the replication stage, the 21 most promising
      signals selected from the discovery stage were tested for their association with
      PCOS. MAIN RESULTS AND THE ROLE OF CHANCE: One novel locus with genome-wide
      significance and seven moderately associated loci for PCOS were identified. The
      strongest association was on chromosome 8q24.2 (rs10505648, OR = 0.52, P = 5.46 *
      10(-8)), and other association signals were located at 4q35.2, 16p13.3, 4p12,
      3q26.33, 9q21.32, 11p13 and 1p22 (P = 5.72 * 10(-6)-6.43 * 10(-5)). The strongest
      signal was located upstream of KHDRBS3, which is associated with telomerase
      activity, and could drive PCOS and related phenotypes. LIMITATIONS, REASONS FOR
      CAUTION: The limitation of our study is the modest sample size used in the
      replication cohort. The limited sample size may contribute to a lack of
      statistical power to detect an association or show a trend in severity. WIDER
      IMPLICATIONS OF THE FINDINGS: Our findings provide new insight into the genetics
      and biological pathways of PCOS and could contribute to the early diagnosis and
      prevention of metabolic and reproductive morbidities. STUDY FUNDING/COMPETING
      INTERESTS: This work was supported in part by the grant from the Korea Centers
      for Disease Control and Prevention (2009-E00591-00). The work was also supported
      by the Ewha Global Top5 Grant 2013 of Ewha Womans University. None of the authors
      has any conflict of interest to declare.

PMID- 25574033
TI  - Recurrent polymyositis-associated lung disease after lung transplantation.
AB  - The association between interstitial lung disease and
      polymyositis/dermatomyositis is well known. It severely affects patients' quality
      of life, worsens prognosis and represents a major risk factor for premature
      death. Current treatment is unclear and therapeutic options are based on case
      series. We report the case of a 15-year old female diagnosed with end-stage lung
      disease associated to polymyositis who received a double lung transplant after 20
      days of extracorporeal membrane oxygenation. She died 9 months later and
      microscopic post-mortem findings revealed recurrence of interstitial lung
      disease. This is the first time that recurrence of polymyositis-associated lung
      disease following lung transplantation is described in the literature. 

PMID- 25574029
TI  - MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic
      coarctation and patent ductus arteriosus.
AB  - Cardiac left ventricular outflow tract (LVOT) defects represent a common but
      heterogeneous subset of congenital heart disease for which gene identification
      has been difficult. We describe a 46,XY,t(1;5)(p36.11;q31.2)dn translocation
      carrier with pervasive developmental delay who also exhibited LVOT defects,
      including bicuspid aortic valve (BAV), coarctation of the aorta (CoA) and patent
      ductus arteriosus (PDA). The 1p breakpoint disrupts the 5' UTR of AHDC1, which
      encodes AT-hook DNA-binding motif containing-1 protein, and AHDC1-truncating
      mutations have recently been described in a syndrome that includes developmental
      delay, but not congenital heart disease [Xia, F., Bainbridge, M.N., Tan, T.Y.,
      Wangler, M.F., Scheuerle, A.E., Zackai, E.H., Harr, M.H., Sutton, V.R., Nalam,
      R.L., Zhu, W. et al. (2014) De Novo truncating mutations in AHDC1 in individuals
      with syndromic expressive language delay, hypotonia, and sleep apnea. Am. J. Hum.
      Genet., 94, 784-789]. On the other hand, the 5q translocation breakpoint disrupts
      the 3' UTR of MATR3, which encodes the nuclear matrix protein Matrin 3, and mouse
      Matr3 is strongly expressed in neural crest, developing heart and great vessels,
      whereas Ahdc1 is not. To further establish MATR3 3' UTR disruption as the cause
      of the proband's LVOT defects, we prepared a mouse Matr3(Gt-ex13) gene trap
      allele that disrupted the 3' portion of the gene. Matr3(Gt-ex13) homozygotes are
      early embryo lethal, but Matr3(Gt-ex13) heterozygotes exhibit incompletely
      penetrant BAV, CoA and PDA phenotypes similar to those in the human proband, as
      well as ventricular septal defect (VSD) and double-outlet right ventricle (DORV).
      Both the human MATR3 translocation breakpoint and the mouse Matr3(Gt-ex13) gene
      trap insertion disturb the polyadenylation of MATR3 transcripts and alter Matrin
      3 protein expression, quantitatively or qualitatively. Thus, subtle perturbations
      in Matrin 3 expression appear to cause similar LVOT defects in human and mouse. 

PMID- 25574034
TI  - Maximal blood flow acceleration analysis in the early diastolic phase for in situ
      internal thoracic artery bypass grafts: a new transit-time flow measurement
      predictor of graft failure following coronary artery bypass grafting.
AB  - OBJECTIVES: Maximal graft flow acceleration (max df/dt) determined by transit
      time flowmetry (TTFM) in the diastolic phase was assessed as a possible predictor
      of graft failure in coronary artery bypass patients. METHODS: Max df/dt was
      retrospectively measured in 57 in situ left internal thoracic artery grafts. TTFM
      data were fitted to a 5-polynomial curve, which was derived from the first
      derivative curve to measure max df/dt (5-polymial max df/dt). Abnormal TTFM was
      defined as a mean flow of <15 ml/min, pulsatility index of >5 or diastolic
      filling ratio of <50%. Postoperative coronary angiography (CAG) or multidetector
      computed tomography (MDCT) was performed within 1 year after surgery. The grafts
      were classified into four groups: Normal TTFM/Patent MDCT/CAG (N/P), Normal
      TTFM/Failing MDCT/CAG (N/F), Abnormal TTFM/Patent MDCT/CAG (Ab-N/P) and Abnormal
      TTFM/Failing MDCT/CAG graft (Ab-N/F). RESULTS: By TTFM, 34 grafts were normal, 5
      of which were occluded on CAG, and 23 grafts were abnormal, six of which were
      occluded on CAG. There were significant differences in 5-polynomial max df/dt
      between each group pair (P < 0.05, Mann-Whitney U-test) except for the N/F:Ab-N/P
      group pair; especially, 5-polynomial max df/dt was significantly lower in the Ab
      N/F group compared with the other groups (Ab-N/F: 0.89 +/- 0.41 vs N/P: 4.74 +/-
      3.18, N/F: 2.23 +/- 0.65, Ab-N/P: 2.70 +/- 1.31 ml/s(2), P < 0.01, Mann-Whitney U
      test). The sensitivity and specificity of 5-polynomial max df/dt were,
      respectively, 72.7 and 80.4% (cut-off value, 1.918 ml/s(2)) for all grafts and
      100 and 88.2% (cut-off value, 1.273 ml/s(2)) for abnormal TTFM grafts.
      CONCLUSIONS: The TTFM 5-polymial max df/dt value in the early diastolic phase may
      be a promising predictor of future graft failure.

PMID- 25574035
TI  - Reclassification of Deinococcus xibeiensis Wang et al. 2010 as a heterotypic
      synonym of Deinococcus wulumuqiensis Wang et al. 2010.
AB  - Two species of the genus Deinococcus, namely Deinococcus wulumuqiensis Wang et
      al. 2010 and Deinococcus xibeiensis Wang et al. 2010, were simultaneously
      proposed and described in the same publication. However, the identical 16S rRNA
      gene sequence of the two type strains strongly raised the probability of their
      relatedness at the species level. Thus, the genomic relatedness of the two
      species of the genus Deinococcus was investigated here to clarify their taxonomic
      status. The high (99.9 %) average nucleotide identity (ANI) between the genome
      sequences of the two type strains suggested that the two species are synonymous.
      Additional phenotypic data including enzymic activities and substrate-utilization
      profiles showed no pronounced differences between the type strains of the two
      species. Data from this study demonstrated that the two taxa constitute a single
      species. According to Rule 42 of the Bacteriological Code, we propose that D.
      xibeiensis Wang et al. 2010 should be reclassified as a subjective heterotypic
      synonym of D. wulumuqiensis Wang et al. 2010. 

PMID- 25574036
TI  - Campylobacter iguaniorum sp. nov., isolated from reptiles.
AB  - During sampling of reptiles for members of the class Epsilonproteobacteria,
      strains representing a member of the genus Campylobacter not belonging to any of
      the established taxa were isolated from lizards and chelonians. Initial amplified
      fragment length polymorphism, PCR and 16S rRNA sequence analysis showed that
      these strains were most closely related to Campylobacter fetus and Campylobacter
      hyointestinalis. A polyphasic study was undertaken to determine the taxonomic
      position of five strains. The strains were characterized by 16S rRNA and atpA
      sequence analysis, matrix-assisted laser desorption ionization time-of-flight
      (MALDI-TOF) mass spectrometry and conventional phenotypic testing. Whole-genome
      sequences were determined for strains 1485E(T) and 2463D, and the average
      nucleotide and amino acid identities were determined for these strains. The
      strains formed a robust phylogenetic clade, divergent from all other species of
      the genus Campylobacter. In contrast to most currently known members of the genus
      Campylobacter, the strains showed growth at ambient temperatures, which might be
      an adaptation to their reptilian hosts. The results of this study clearly show
      that these strains isolated from reptiles represent a novel species within the
      genus Campylobacter, for which the name Campylobacter iguaniorum sp. nov. is
      proposed. The type strain is 1485E(T) ( = LMG 28143(T) = CCUG 66346(T)). 

PMID- 25574037
TI  - Pseudomonas zhaodongensis sp. nov., isolated from saline and alkaline soils.
AB  - Strain NEAU-ST5-21(T) was isolated from saline and alkaline soils in Zhaodong
      City, Heilongjiang Province, China. It was aerobic, Gram-stain-negative, rod
      shaped and motile with a polar flagellum. It produced yellow-orange colonies with
      a smooth surface, and grew in the presence of 0-5 % (w/v) NaCl (optimum 0 %,
      w/v), at temperatures of 20-40  degrees C (optimum 28  degrees C) and at pH 7-11
      (optimum pH 7). Phylogenetic analyses based on the separate 16S rRNA gene
      sequences and concatenated 16S rRNA, gyrB and rpoD gene sequences indicated that
      strain NEAU-ST5-21(T) belongs to the genus Pseudomonas in the class
      Gammaproteobacteria. The most closely related species is Pseudomonas
      xanthomarina, whose type strain (KMM 1447(T)) showed gene sequence similarities
      of 99.0 % for 16S rRNA, 81.8 % for gyrB and 85.0 % for rpoD with strain NEAU-ST5
      21(T). DNA-DNA hybridization values between strain NEAU-ST5-21(T) and P.
      xanthomarina DSM 18231(T), Pseudomonas kunmingensis CGMCC 1.12273(T), Pseudomonas
      stutzeri DSM 5190(T), Pseudomonas oleovorans subsp. lubricantis DSM 21016(T),
      Pseudomomas chengduensis CGMCC 2318(T), Pseudomonas alcaliphila DSM 17744(T) and
      Pseudomonas toyotomiensis DSM 26169(T) were 52+/-0 % to 25+/-2 %. The DNA G+C
      content of strain NEAU-ST5-21(T) was 65 mol%. The major fatty acids (>10 %) were
      C18 : 1omega7c and/or C18 : 1omega6c, C16 : 1omega7c and/or C16 : 1omega6c and
      C16 : 0, the predominant respiratory quinone was ubiquinone 9, and polar lipids
      consisted of diphosphatidylglycerol, phosphatidylethanolamine, one unknown
      phospholipid, phosphatidylglycerol, one unknown aminolipid, one unknown lipid and
      a glycolipid. The proposed name is Pseudomonas zhaodongensis sp. nov., NEAU-ST5
      21(T) ( = ACCC 06362(T) = DSM 27559(T)) being the type strain. 

PMID- 25574038
TI  - Should 'Candidatus Phytoplasma' be retained within the order Acholeplasmatales?
AB  - Phytoplasmas are a diverse but phylogenetically coherent group of cell-wall-less
      bacteria affiliated with the class Mollicutes. Due to difficulties in
      establishing axenic culture, phytoplasmas were assigned to a provisional genus,
      'Candidatus Phytoplasma', and the genus was embraced within the order
      Acholeplasmatales. However, phytoplasmas differ significantly from species of the
      genus Acholeplasma in their habitat specificities, modes of life, metabolic
      capabilities, genomic architectures, and phylogenetic positions. This
      communication describes the unique ecological, nutritional, biochemical, genomic
      and phylogenetic properties that distinguish phytoplasmas from species of the
      genus Acholeplasma and all other taxa in the class Mollicutes. Since such
      distinguishing properties of the phytoplasmas are not referable to the
      descriptions of the order Acholeplasmatales and of all other existing orders,
      namely Mycoplasmatales, Entomoplasmatales and Anaeroplasmatales, this
      communication raises the question of whether 'Candidatus Phytoplasma' should be
      retained in the order Acholeplasmatales or whether a novel provisional order and
      family should be created to accommodate the genus 'Ca. Phytoplasma'. 

PMID- 25574040
TI  - Quality of care in primary health care settings in the Eastern Mediterranean
      region: a systematic review of the literature.
AB  - PURPOSE: This systematic review aims at offering a comprehensive synthesis of
      studies addressing quality of care in the primary healthcare (PHC) sector of the
      Eastern Mediterranean Region (EMR). DATA SOURCES: A systematic search was
      conducted using Medline, Embase and Global Health Library (IMEMR) electronic
      databases to identify studies related to quality in PHC between years 2000 and
      2012. STUDY SELECTION/DATA EXTRACTION: One hundred and fifty-nine (159) studies
      fulfilled the eligibility criteria. Each paper was independently reviewed by two
      reviewers, and the following information was extracted/calculated: dimension of
      care investigated (structure, processes and outcomes), focus, disease groups,
      study design, sample size, unit of analysis, response rate, country, setting
      (public or private) and level of rigor (LOR) score. RESULTS OF DATA SYNTHESIS:
      Most of the studies were descriptive/cross-sectional in nature with a relatively
      modest LOR score. Assessment of quality of care revealed that the process
      dimension of quality, specifically clinical practice and patient-provider
      relationship, is an area of major concern. However, interventions targeting
      enhanced quality in PHC in the EMR countries had favorable and effective outcomes
      in terms of clinical practice. CONCLUSION: These findings highlight gaps in
      evidence on quality in PHC in the EMR; such evidence is key for decision-making.
      Researchers and policy-makers should address these gaps to generate
      contextualized information and knowledge that ensures relevance and targeted high
      impact interventions.

PMID- 25574039
TI  - NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in
      experimental autoimmune encephalomyelitis in mice.
AB  - Active vitamin D [1,25-dihydroxyvitamin D3 (1,25D3)] blocks the development of
      experimental autoimmune diseases. However, the molecular and immunobiological
      mechanisms underlying 1,25D3's anti-inflammatory properties are not fully
      understood. We employed a murine model of experimental autoimmune
      encephalomyelitis (EAE) in order to determine the role of NKT cells in 1,25D3
      mediated protection from EAE. Wild-type (WT) mice or mice lacking all NKT cells
      (CD1d(-/-)) or invariant NKT cells (Jalpha18(-/-)) were fed control or 1,25D3
      supplemented diets. All mice fed with the control diet developed severe EAE.
      1,25D3 treatment of WT mice protected them from developing EAE. CD1d(-/-) and
      Jalpha18(-/-) mice treated with 1,25D3 were not protected to the same extent as
      WT mice. Myelin oligodendrocyte glycoprotein-specific IL-17 and IFN-gamma
      production was significantly reduced in 1,25D3 WT mice compared with WT but was
      not decreased in 1,25D3 CD1d(-/-) mice compared with CD1d(-/-) mice. IL-4(-/-)
      mice were utilized to determine how IL-4 deficiency affects susceptibility to
      EAE. IL-4(-/-) mice were not protected from developing EAE by alpha
      galactosylceramide (alpha-GalCer) or 1,25D3 treatment. Furthermore, 1,25D3
      treatment of splenocytes in vitro decreased alpha-GalCer-induced IL-17 and
      increased IL-4, IL-5 and IL-10 production. 1,25D3 alters the cytokine profile of
      invariant NKT cells in vitro. These studies demonstrate that NKT cells are
      important mediators of 1,25D3-induced protection from EAE in mice and NKT cell
      derived IL-4 may be an important factor in providing this protection. 

PMID- 25574041
TI  - Analysis of retinal nonperfusion using depth-integrated optical coherence
      tomography images in eyes with branch retinal vein occlusion.
AB  - PURPOSE: To assess the morphology of areas of complete retinal nonperfusion in
      eyes with branch retinal vein occlusion (BRVO) by en face images of optical
      coherence tomography (OCT). METHODS: Forty-six eyes with BRVO that underwent
      swept-source OCT (SS-OCT) and fluorescein angiography were enrolled. Depth
      integrated images of the neural retina delineated by automated segmentation
      algorithm were obtained using SS-OCT. The findings in a 6 * 6-mm area on en face
      SS-OCT scans at the area of retinal nonperfusion were evaluated. RESULTS: Retinal
      nonperfusion was detected in 25 eyes. Of these, 20 (80%) eyes had multiple
      concaves of low reflectivity within an area of reticular high reflectivity
      (honeycomb sign) on depth-integrated images at the area corresponding to retinal
      nonperfusion. The mean area of retinal nonperfusion and honeycomb sign were 6.72
      +/- 4.10 mm2 and 4.19 +/- 3.37 mm2, respectively. The area of retinal
      nonperfusion was correlated significantly (r = 0.53, P < 0.001) with the area of
      the honeycomb sign. The mean retinal thickness in eyes with a honeycomb sign
      increased significantly (P = 0.017) compared with eyes without a honeycomb sign.
      Furthermore, after anti-VEGF injection, the mean area of honeycomb sign decreased
      significantly (P = 0.0013), from 4.23 mm(2) to 0.48 mm(2). CONCLUSIONS: Depth
      integrated OCT images with automated layer segmentation showed a two-dimensional
      honeycomb-like structure in retinal nonperfusion with retinal edema. In eyes with
      BRVO, the thickness of retina did not decrease but increased due to retinal cyst
      in spite of neural retinal thinning.

PMID- 25574042
TI  - Rates of adverse events with hydrogel and silicone hydrogel daily disposable
      lenses in a large postmarket surveillance registry: the TEMPO Registry.
AB  - PURPOSE: To report annualized adverse events (AEs) including corneal infiltrative
      events (CIEs) with use of silicone hydrogel (SiHyDD) and hydrogel daily
      disposable (HydDD) soft contact lenses (SCLs) in the 1*DAY ACUVUE TruEye or 1*DAY
      ACUVUE MOIST Performance Overview (TEMPO) Registry (NCT01467557). METHODS:
      Annualized incidence of symptomatic daily disposable (DD)-related AEs was
      calculated from 3064 surveys from 1171 subjects (601 SiHyDD and 570 HydDD, 31.8
      +/- 13.5 years, 68% female) during 1 year. Three independent experts adjudicated
      potential AE cases. Demographics were compared between wearers with and without
      AEs. RESULTS: The registry tracked 960.3 years of lens wear: SiHyDD 489.4 years
      and HydDD 470.9 years. In that period, the 601 SiHyDD wearers reported eight AEs
      with office visits (1.6%/y; 2 CIEs, 0.4%/y), eight (1.6%/y) without office
      visits, and four AEs unrelated to SCLs (0.8%/y) (SiHyDD wearers with AEs; 44.8 +/
      12.5 years; 75% female). The 570 HyDD wearers reported three AEs with office
      visits (0.6%/y; no CIEs), five without office visits (1.1%/y), and one non-SCL
      related AE (0.2%/y) (HydDD wearers with AEs; 26.3 +/- 8.0 years; 100% female).
      These CIE rates are significantly lower than the lowest estimate of 3.3% from
      prior studies. Wearers with SiHyDD-related AEs were significantly older than
      unaffected wearers (P = 0.02), but not for HydDD-related AEs. CONCLUSIONS: The
      CIE rates of 0.4% and 0% with these DD lenses are significantly lower than rates
      reported with reusable SCLs (3%-4%/y), indicating improved safety outcomes with
      these DD lenses. Compared to unaffected wearers, SiHyDD lens wearers with AEs
      requiring clinical visits were significantly older. (ClinicalTrials.gov number,
      NCT01467557.).

PMID- 25574043
TI  - Role of glutathione peroxidase 4 in conjunctival epithelial cells.
AB  - PURPOSE: The purpose of the present study was to investigate the role of
      glutathione peroxidase 4 (GPx4) in conjunctival epithelial cells. METHODS: An
      immortalized human conjunctival epithelial cell line was used. Cells were
      transfected with catalase, GPx1, GPx4, SOD1, SOD2, or control siRNA. Knockdown
      was confirmed by RT-PCR and immunoblotting. The cytotoxicity induced by knockdown
      of these antioxidant enzymes was examined by assay of LDH activity. Furthermore,
      evaluations of lipid peroxidation, cellular levels of reactive oxygen species,
      cell proliferation, and apoptosis were conducted in cells treated with GPx4 or
      control siRNA. In oxidative stress study, cells treated with GPx4 or control
      siRNA were applied with hydrogen peroxide or ferric sulfide, and their
      cytotoxicity was evaluated by assay of LDH activity. RESULTS: Small interfering
      RNA of catalase, GPx1, GPx4, SOD1, and SOD2 siRNA remarkably inhibited the mRNA
      and protein expression of each gene. Knockdown of GPx4 and SOD1 but not catalase,
      GPx1, and SOD2 significantly induced cytotoxicity. Glutathione peroxidase 4
      knockdown increased lipid oxidation and reactive oxygen species. The
      proliferation of GPx4 siRNA-treated cells was reduced compared with control siRNA
      treated cells. Moreover, cell death in GPx4 siRNA-treated cells was characterized
      by positive staining for annexin V. In an oxidation stress study, GPx4 siRNA
      knockdown enhanced the cytotoxicity induced by hydrogen peroxide or ferric
      sulfide. CONCLUSION: These results suggest that GPx4 is essential for maintaining
      oxidative homeostasis and keeping defense against oxidative stress in
      conjunctival epithelial cells.

PMID- 25574045
TI  - Infrared imaging of meibomian glands and evaluation of the lipid layer in
      Sjogren's syndrome patients and nondry eye controls.
AB  - PURPOSE: The purpose of this study was to evaluate meibomian gland dropout and
      lipid layer thickness (LLT) in patients with and without Sjogren's syndrome dry
      eye (SS). METHODS: We recruited 11 participants with SS (males/females [M/F],
      1:10; mean age = 56.0 +/- 9.1 years) and 10 control subjects without dry eye
      (M/F, 3:7; mean age = 58.5 +/- 4.7 years). All participants completed the Ocular
      Surface Disease Index (OSDI) questionnaire. The LLT was assessed using the
      Tearscope Plus based on the appearance of the lipid layer. Noninvasive tear break
      up time (NITBUT) also was measured. The lower and upper lids were everted, and
      the meibomian glands were imaged using the infrared camera of the Keratograph 4.
      A meibomian gland dropout score due to gland loss was obtained. Statistical
      analysis was conducted using the Mann-Whitney U test and correlations were
      determined using Spearman rank correlations. RESULTS: Of the SS participants,
      100% reported ocular and oral dryness symptoms in the AECC questionnaire. The SS
      group recorded a higher OSDI score (median = 48.00, interquartile range [IQR]
      23.0-56.2 vs. 2.1, IQR 0.0-2.6; P < 0.001), reduced LLT (median [IQR] = 15.0
      [15.0-15.0] vs. 60.0 [45.0-100.0] nm; P = 0.001), and lower NITBUT (median [IQR]
      = 3.7 [2.5-4.2] vs. 9.5 [6.4-17.6] sec; P < 0.001) compared to the controls.
      Digital meibomian gland dropout score (% dropout) was significantly higher for
      the SS group (16.0% [IQR 12.1-40.0%] vs. 6.7% [IQR 1.5-12.7%]; P = 0.01).
      Subjective meibomian gland dropout score (0-6 score) was significantly higher for
      the SS group (median [IQR] = 1.5 [1.0-4.0] vs. 1.0 [0.0-1.25]; P = 0.03).
      CONCLUSIONS: Patients with SS showed higher meibomian gland dropout scores and
      reduced LLT and NITBUT, which likely contribute to the severe dry eye symptoms
      reported by SS subjects.

PMID- 25574044
TI  - Metanx and early stages of diabetic retinopathy.
AB  - PURPOSE: l-Methylfolate, pyridoxal 5'-phosphate, and methylcobalamin,
      individually have been reported to have beneficial effects on diabetes-induced
      defects. The possibility that combining these therapeutic approaches might have
      additional benefit led us to investigate the effect of Metanx against development
      of early stages of diabetic retinopathy in a mouse model. METHODS: C57BL/6J mice
      were made diabetic with streptozotocin, and some were given Metanx (a combination
      food product) mixed in the food at a dose of 5 mg/kg of body weight. Mice were
      killed at 2 months and 10 months of study for assessment of retinal function,
      retinal vascular histopathology, accumulation of albumin in neural retina, and
      biochemical and physiological abnormalities in retina. RESULTS: Two months of
      diabetes significantly increased leukostasis within retinal vessels and
      superoxide generation by the retina. Diabetes also significantly increased
      expression of intercellular adhesion molecule-1 (ICAM-1) and phosphorylation of
      IkappaB. Daily consumption of Metanx significantly inhibited all of these
      abnormalities. Ten months of diabetes significantly increased the degeneration of
      retinal capillaries and impaired visual function (spatial frequency threshold
      (SFT) and a parameter of contrast sensitivity) compared to nondiabetic controls.
      Daily consumption of Metanx for 10 months inhibited impairment of SFT but had no
      significant beneficial effect on capillary degeneration, pericyte loss, or the
      estimate of contrast sensitivity. CONCLUSIONS: Metanx inhibited a diabetes
      induced defect in retinal spatial frequency threshold and inhibited measures of
      oxidative stress and inflammation. It had no significant effect on contrast
      sensitivity or retinal capillary degeneration. Nutritional management with Metanx
      may help inhibit diabetes-induced defects in visual function.

PMID- 25574046
TI  - Quantitative analysis of iris changes following mydriasis in subjects with
      different mechanisms of angle closure.
AB  - PURPOSE: We estimate and compare change in iris cross-sectional area (IA) after
      physiologic and pharmacologic mydriasis in subjects with different dominant
      mechanisms for primary angle closure. METHODS: Anterior segment optical coherence
      tomography (AS-OCT) measurements in light, dark, and following pharmacologic
      dilation were obtained on primary angle closure suspects (PACS), primary angle
      closure (PAC), and primary angle closure glaucoma (PACG) examined during the 5
      year follow-up of the Handan Eye Study. Subjects were categorized into three
      subgroups according to their dominant angle closure (AC) mechanisms as determined
      by AS-OCT: pupillary block (PB), plateau iris configuration (PIC), and thick
      peripheral iris roll (TPIR). The IA and other biometric parameters measured using
      the Zhongshan Angle Assessment Program in the right eyes of all subjects were
      analyzed. RESULTS: A total of 364 right eyes of subjects with PACS (333), and
      PAC/PACG (31) was included in the analysis. Significant differences in the change
      of IAs (P = 0.030), IA loss per mm pupil diameter (PD) increase (P = 0.001) in
      light versus pharmacologic dilation, and IA loss per mm PD increase (P = 0.011)
      from dark versus pharmacologic dilation were observed among the three groups. The
      smallest decrease occurred in the PB group. CONCLUSIONS: There are significant
      differences in IA and IA loss per mm of pupil change following physiologic or
      pharmacologic mydriasis in Chinese subjects with dissimilar dominant mechanisms
      for AC. Dynamic iris change may have a more important role in angle closure where
      PB is the dominant mechanism.

PMID- 25574047
TI  - Knockout of alphaA-crystallin inhibits ocular neovascularization.
AB  - PURPOSE: The present study aimed to investigate the effects of alphaA-crystallin
      on pathologic ocular neovascularization. METHODS: Human umbilical vein
      endothelial cells (HUVECs) were used for the in vitro study, and alphaA
      crystallin-knockout (CRYAA[-/-]) mice were used for the in vivo study. alphaA
      crystallin was knocked down in HUVECs by using a specific small interfering RNA
      (siRNA), and the effects of alphaA-crystallin knockdown on proliferation,
      migration, tube formation, and apoptosis were evaluated. Enzyme-linked
      immunosorbent assays were performed to investigate extracellular concentrations
      of vascular endothelial growth factor (VEGF). In vivo mouse models of oxygen
      induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV)
      were generated by using CRYAA(-/-) mice. The nonperfused area in the OIR model
      was measured in flat-mounted retinas, and angiogenesis resulting in CNV was
      evaluated in retinal sections. Western blot analysis was performed to investigate
      the phosphorylation status of vascular endothelial growth factor receptor 2
      (VEGFR2, high affinity receptor for VEGF), AKT, PLCgamma1, FAK, Src, p42/p44MAPK,
      p38MAPK, caspase-3, and caspase-9 in cultured HUVECs, as well as in the OIR and
      CNV models. RESULTS: The CRYAA siRNA not only induced HUVEC apoptosis but also
      inhibited exogenous and endogenous VEGF-induced cell activities, including
      proliferation, migration, and tube formation. Pathologic neovascularization was
      attenuated in the CRYAA(-/-) murine OIR and CNV models. Both in vitro and in
      vivo, the inhibition of angiogenesis was mediated by the suppression of VEGF
      secretion and the inhibition of the VEGFR2 signaling pathway; VEGFR2, AKT,
      PLCgamma1, FAK, Src, p42/p44 MAPK, and p38 MAPK all showed reduced
      phosphorylation levels. In addition, CRYAA knockout led to increased levels of
      cleaved caspase-9 and caspase-3. CONCLUSIONS: Knockout of alphaA-crystallin
      inhibited pathologic neovascularization through the VEGF and VEGFR2 signaling
      pathways both in vitro and in vivo. These results suggest that alphaA-crystallin
      could be a novel pharmaceutical target for the prevention of ocular
      neovascularization.

PMID- 25574048
TI  - Adaptive optics imaging of healthy and abnormal regions of retinal nerve fiber
      bundles of patients with glaucoma.
AB  - PURPOSE: To better understand the nature of glaucomatous damage of the macula,
      especially the structural changes seen between relatively healthy and clearly
      abnormal (AB) retinal regions, using an adaptive optics scanning light
      ophthalmoscope (AO-SLO). METHODS: Adaptive optics SLO images and optical
      coherence tomography (OCT) vertical line scans were obtained on one eye of seven
      glaucoma patients, with relatively deep local arcuate defects on the 10-2 visual
      field test in one (six eyes) or both hemifields (one eye). Based on the OCT
      images, the retinal nerve fiber (RNF) layer was divided into two regions: (1)
      within normal limits (WNL), relative RNF layer thickness within mean control
      values +/-2 SD; and (2) AB, relative thickness less than -2 SD value. RESULTS: As
      seen on AO-SLO, the pattern of AB RNF bundles near the border of the WNL and AB
      regions differed across eyes. There were normal-appearing bundles in the WNL
      region of all eyes and AB-appearing bundles near the border with the AB region.
      This region with AB bundles ranged in extent from a few bundles to the entire AB
      region in the case of one eye. All other eyes had a large AB region without
      bundles. However, in two of these eyes, a few bundles were seen within this
      region of otherwise missing bundles. CONCLUSIONS: The AO-SLO images revealed
      details of glaucomatous damage that are difficult, if not impossible, to see with
      current OCT technology. Adaptive optics SLO may prove useful in following
      progression in clinical trials, or in disease management, if AO-SLO becomes
      widely available and easy to use.

PMID- 25574050
TI  - Inhibition of RAP1 enhances corneal recovery following alkali injury.
AB  - PURPOSE: Recently, RAP1 (Telomeric Repeat Binding Factor 2, Interacting Protein
      [TERF2IP]) was discovered as a modulator that selectively regulates nuclear
      factor light chain kappa enhancer of activated B cells (NFkappaB) signaling. The
      roles of RAP1 in regulation of inflammation and angiogenesis for corneal recovery
      following corneal injury remain poorly understood. The effects of RAP1 deletion
      on corneal resurfacing and neovascularization in a corneal alkali burn mouse
      model were examined. METHODS: Corneal defects and neovascularization were induced
      in vivo by infliction of an alkali burn to the cornea with 1 N sodium hydroxide
      solution in RAP1 knock-out (RKO) and wild-type (RWT) mice. Corneal resurfacing
      was evaluated using slit-lamp biomicroscopy. Neovascularization following injury
      was evaluated by bright view biomicroscopy and immunofluorescence staining with
      the endothelial marker platelet endothelial cell adhesion molecule (PECAM). The
      cytokine profiles of corneal tissue involved in inflammation and
      neovascularization following injury was compared between RKO and RWT mice.
      Corneal epithelial cells were isolated for classic scratch wound healing assay
      and further testing with lipopolysaccharide stimulation. RESULTS: Resurfacing of
      the burned cornea was accelerated and angiogenesis was suppressed, faster
      recovery of corneal epithelial cells from classic scratch wound healing and
      superior tolerance of lipopolysaccharides challenge was observed in the RKO
      compared to RWT. Molecular investigation revealed that deletion of RAP1 reduced
      upregulation of inflammatory cytokine (IL1A), finely regulated the expression of
      angiogenic factor (VEGF), and antiangiogenic factor (PEDF), following injury for
      better corneal recovery. CONCLUSIONS: Deficiency of RAP1 facilitates corneal
      recovery after injury. Specificity of RAP1 inhibition may lead to design of
      specific inhibitors of NFkappaB in the treatment of ocular injuries.

PMID- 25574051
TI  - Circadian control of the pupillary light responses in an avian model of
      blindness, the GUCY1* chickens.
AB  - PURPOSE: The vertebrate inner retina has a subset of intrinsically photosensitive
      retinal ganglion cells (ipRGCs) that express the nonvisual photopigment
      melanopsin. The intrinsically photosensitive retinal ganglion cells send light
      information from the environment to the brain to control, among other parameters,
      the amount of energy entering the eyes through the pupillary light reflex (PLR).
      A daily variation in the PLR in both mice and humans has recently been shown,
      indicating circadian control of this response. In a previous work involving the
      sensitivity spectra for the PLR, we showed that blind chickens (GUCY1*) display
      the highest sensitivity to light of 480 nm. The aim of the present study was to
      evaluate the potential circadian control of PLRs in blind birds under scotopic
      conditions. METHODS: Circadian PLR was performed on GUCY1* chickens with lights
      of different wavelengths (white or blue light of 475 nm) under scotopic
      conditions. RESULTS: We found a significant daily variation in the PLRs of
      chickens exposed to white or blue light of 475 nm, with increased sensitivity at
      circadian time 6 during the subjective day. CONCLUSIONS: Our observations clearly
      point to circadian control of PLRs even in blindness, strongly indicating that
      both the entry of light into the eyes and its quality are differentially
      regulated during the day in diurnal animals.

PMID- 25574049
TI  - Oxidative stress and light-evoked responses of the posterior segment in a mouse
      model of diabetic retinopathy.
AB  - PURPOSE: To test the hypothesis that in a mouse model of diabetic retinopathy,
      oxidative stress is linked with impaired light-evoked expansion of choroidal
      thickness and subretinal space (SRS). METHODS: We examined nondiabetic mice (wild
      type, wt) with and without administration of manganese, nondiabetic mice
      deficient in rod phototransduction (transducin alpha knockout; GNAT1(-/-)), and
      diabetic mice (untreated or treated with the antioxidant alpha-lipoic acid
      [LPA]). Magnetic resonance imaging (MRI) was used to measure light-evoked
      increases in choroidal thickness and the apparent diffusion coefficient (ADC) at
      88% to 100% depth into the retina (i.e., the SRS layer). RESULTS: Choroidal
      thickness values were similar (P > 0.05) between all untreated nondiabetic dark
      adapted groups and increased significantly (P < 0.05) with light; this expansion
      was subnormal (P < 0.05) in both diabetic groups. Apparent diffusion coefficient
      values in the SRS layer robustly increased (P < 0.05) in a light duration
      dependent manner, and this effect was independent of the presence of Mn(2+). The
      light-stimulated increase in ADC at the location of the SRS was absent in GNAT1(
      /-) and diabetic mice (P > 0.05). In diabetic mice, the light-dependent increase
      in SRS ADC was significantly (P < 0.05) restored with LPA. CONCLUSIONS: Apparent
      diffusion coefficient MRI is a sensitive method for evaluating choroid thickness
      and its light-evoked expansion together with phototransduction-dependent changes
      in the SRS layer in mice in vivo. Because ADC MRI exploits an endogenous contrast
      mechanism, its translational potential is promising; it can also be performed in
      concert with manganese-enhanced MRI (MEMRI). Our data support a link between
      diabetes-related oxidative stress and rod, but not choroidal, pathophysiology.

PMID- 25574052
TI  - Automatic identification of reticular pseudodrusen using multimodal retinal image
      analysis.
AB  - PURPOSE: To examine human performance and agreement on reticular pseudodrusen
      (RPD) detection and quantification by using single- and multimodality grading
      protocols and to describe and evaluate a machine learning system for the
      automatic detection and quantification of reticular pseudodrusen by using single-
      and multimodality information. METHODS: Color fundus, fundus autofluoresence, and
      near-infrared images of 278 eyes from 230 patients with or without presence of
      RPD were used in this study. All eyes were scored for presence of RPD during
      single- and multimodality setups by two experienced observers and a developed
      machine learning system. Furthermore, automatic quantification of RPD area was
      performed by the proposed system and compared with human delineations. RESULTS:
      Observers obtained a higher performance and better interobserver agreement for
      RPD detection with multimodality grading, achieving areas under the receiver
      operating characteristic (ROC) curve of 0.940 and 0.958, and a kappa agreement of
      0.911. The proposed automatic system achieved an area under the ROC of 0.941 with
      a multimodality setup. Automatic RPD quantification resulted in an intraclass
      correlation (ICC) value of 0.704, which was comparable with ICC values obtained
      between single-modality manual delineations. CONCLUSIONS: Observer performance
      and agreement for RPD identification improved significantly by using a
      multimodality grading approach. The developed automatic system showed similar
      performance as observers, and automatic RPD area quantification was in
      concordance with manual delineations. The proposed automatic system allows for a
      fast and accurate identification and quantification of RPD, opening the way for
      efficient quantitative imaging biomarkers in large data set analysis.

PMID- 25574053
TI  - Immunomodulatory effects of galectin-1 on an IgE-mediated allergic conjunctivitis
      model.
AB  - PURPOSE: Galectin (Gal)-1, a lectin found at sites of immune privilege with
      critical role in the inflammation, has been poorly investigated in the ocular
      inflammatory diseases. Here, we evaluated the therapeutic potential of Gal-1 in
      ocular allergy using a model of ovalbumin (OVA)-induced AC. METHODS: OVA
      immunized BALB/c male mice were challenged with eye drops containing OVA on days
      14 through 16 with a subset of animals pretreated intraperitoneally with
      recombinant Gal-1 (rGal-1) or dexamethasone (Dex). RESULTS: Recombinant Gal-1 and
      Dex administration on days 14 through 16 was effective in reducing the clinical
      signs of allergic conjunctivitis (AC), plasma anti-OVA IgE levels, Th2 (IL-4 and
      IL-13), and eotaxin/RANTES levels in the lymph nodes. Four hours after the last
      OVA challenge, rGal-1 markedly increased Gal-1 endogenous levels in the
      conjunctiva, and provoked eosinophilia, which persisted at 24 hours. Recombinant
      Gal-1 had no effect on eosinophil activation, as evidenced by the similar pattern
      of peroxidase eosinophil expression between cells of rGal-1-treated and untreated
      AC groups. Conjunctival migrated eosinophils and neutrophils exhibited high
      levels of Gal-1 and beta2-integrin, with points of colocalization, in the rGal-1
      treated groups. These different effects observed for rGal-1 were correlated with
      elevated levels of activated ERK and p38 at 4 hours, and diminished levels of
      activated JNK and p38 at 24 hours in the eyes. CONCLUSIONS: Gal-1 has an
      important role in ocular allergic inflammation and represents a potential target
      for the development of new therapeutic strategies in eye diseases.

PMID- 25574054
TI  - Association between body composition and retinal vascular caliber in children and
      adolescents.
AB  - PURPOSE: To elucidate the relationship between body composition and retinal
      vascular caliber (RVC) in children and adolescents. METHODS: Participants aged 7
      to 19 years were recruited from the Guangzhou Twin Eye Study cohort. Retinal
      vascular caliber was measured cross-sectionally from retinal images using a
      computer-aided program. The data were expressed as the central retinal arteriolar
      equivalent (CRAE) and central retinal venular equivalent (CRVE). Triceps skinfold
      thickness (TSFT) was measured using a skinfold caliper. Body composition was
      obtained through bioelectrical impedance analysis, providing fat mass (FM), fat
      mass index (FMI), fat-free mass (FFM), fat-free mass index (FFMI), body water
      mass (BWM), body water percentage (BWP), basal metabolic rate (BMR), and trunk
      fat percentage (TFP). RESULTS: A total of 731 participants were included. Among
      the younger children (7-11 years), there was no significant association between
      body composition and RVC (all P > 0.05). However, for the older children (12-19
      years), increasing FM, FMI, TFP, TSFT, and BMI were associated with CRAE
      negatively (beta = -0.20, -0.68, -0.18, -0.17, and -0.48, respectively, all P <
      0.05) and with CRVE positively (beta = 0.47, 1.26, 0.34, 0.37, and 0.78,
      respectively, all P < 0.05), after adjusting for age, sex, axial length, mean
      arterial blood pressure, and the fellow vascular diameter. In contrast, increase
      in BWP was associated with larger CRAE (beta = 0.33, P = 0.001) and smaller CRVE
      (beta = -0.64, P < 0.001). Similar associations also were observed in the
      analyses when the body composition parameters were divided into quartiles (all P
      < 0.05). CONCLUSIONS: In adolescents, greater body fat deposition is related to
      narrower retinal arterioles and wider retinal venules, and higher body water
      proportion is associated with retinal arterioles widening and retinal venules
      narrowing. Even during childhood, body composition might have an association with
      systemic microvasculature.

PMID- 25574055
TI  - Correlation between ganglion cell layer thinning and poor visual function after
      resolution of diabetic macular edema.
AB  - PURPOSE: To assess the thickness of the ganglion cell-inner plexiform layer
      (GCIPL) in eyes with resolved diabetic macular edema (DME), using spectral-domain
      optical coherence tomography (SD-OCT), and its relationship with the visual
      function. METHODS: This retrospective observational case-control cohort study
      included eyes of diabetic patients with resolved DME (r-DME eyes), that is,
      normal central macular thickness (CMT) after treatment of DME, and eyes of aged
      matched diabetic patients without maculopathy (no-DME eyes). The GCIPL thickness
      was measured on a macular cube SD-OCT scan using a specific automatic
      segmentation algorithm. Linear regression analyses were performed to determine
      the association between the GCIPL thickness and the visual acuity (VA) measured
      at the time of the OCT measurement. RESULTS: Average GCIPL thickness was reduced
      in r-DME eyes compared with no-DME eyes (74 +/- 14 MUm versus 83.2 +/- 6 MUm, P =
      0.0189), whereas no significant difference in mean CMT was observed (260.0 +/- 34
      MUm versus 265.7 +/- 22 MUm, P = 0.847). Visual acuity significantly correlated
      with the average GCIPL thickness (r = 0.8, P < 0.0001) and minimum GCIPL
      thickness (r = 0.84, P < 0.0001) in r-DME eyes. CONCLUSIONS: Despite favorable
      anatomic response and restoration of a CMT in the range of normal values after
      resolution of DME, the GCIPL thickness in r-DME eyes was lower than that in no
      DME eyes and correlated with the VA. These results suggest that inner retinal
      alterations occurring in patients with DME and diabetic retinopathy may lead to
      visual deficiency persisting after treatment.

PMID- 25574056
TI  - Sildenafil-induced reversible impairment of rod and cone phototransduction in
      monkeys.
AB  - PURPOSE: To investigate functional alteration of the retina induced by sildenafil
      in monkeys. METHODS: Sildenafil was administered intravenously to cynomolgus
      monkeys at dose levels of 0, 1, 3, and 10 mg/kg, and standard full-field
      electroretinograms (ERGs) were recorded. The rod and cone a-waves in response to
      high-intensity flashes were also analyzed by the a-wave fitting model (a-wave
      analysis). Additionally, the photopic negative responses were recorded. RESULTS:
      Sildenafil at 3 mg/kg or more induced the following alterations in the standard
      full-field ERGs immediately after dosing: delayed b-wave in the rod response;
      delayed a-wave in the combined rod-cone response; and attenuated b-waves in the
      single-flash cone response and in the 30 Hz flicker. Additionally, the following
      changes were observed in the 10 mg/kg group: attenuated b-wave in the rod
      response; attenuated a-wave and delayed b-wave in the combined rod-cone response;
      delayed oscillatory potentials; and attenuated and delayed a-wave in the single
      flash cone response. In the a-wave analysis immediately after dosing, sildenafil
      selectively decreased the sensitivity parameter (S) in the cone a-wave at 3
      mg/kg, and in both the rod and cone a-waves at 10 mg/kg. The S value was highly
      correlated with plasma sildenafil concentration. The above changes fully
      recovered 24 hours after dosing. CONCLUSIONS: Sildenafil produced reversible
      impairment of the rod and cone phototransduction in monkeys. Meanwhile,
      involvement of the postreceptoral retinal components was suggested. These
      findings contribute to the clarification of sildenafil-induced visual
      disturbances. It is suggested that the photoreceptors are predominantly, but not
      exclusively, affected in the retina of humans with sildenafil-induced visual
      disturbances.

PMID- 25574058
TI  - Modeling of Pixelated Detector in SPECT Pinhole Reconstruction.
AB  - A challenge for the pixelated detector is that the detector response of a gamma
      ray photon varies with the incident angle and the incident location within a
      crystal. The normalization map obtained by measuring the flood of a point-source
      at a large distance can lead to artifacts in reconstructed images. In this work,
      we investigated a method of generating normalization maps by ray-tracing through
      the pixelated detector based on the imaging geometry and the photo-peak energy
      for the specific isotope. The normalization is defined for each pinhole as the
      normalized detector response for a point-source placed at the focal point of the
      pinhole. Ray-tracing is used to generate the ideal flood image for a point
      source. Each crystal pitch area on the back of the detector is divided into 60 *
      60 sub-pixels. Lines are obtained by connecting between a point-source and the
      centers of sub-pixels inside each crystal pitch area. For each line ray-tracing
      starts from the entrance point at the detector face and ends at the center of a
      sub-pixel on the back of the detector. Only the attenuation by NaI(Tl) crystals
      along each ray is assumed to contribute directly to the flood image. The
      attenuation by the silica (SiO2) reflector is also included in the ray-tracing.
      To calculate the normalization for a pinhole, we need to calculate the ideal
      flood for a point-source at 360 mm distance (where the point-source was placed
      for the regular flood measurement) and the ideal flood image for the point-source
      at the pinhole focal point, together with the flood measurement at 360 mm
      distance. The normalizations are incorporated in the iterative OSEM
      reconstruction as a component of the projection matrix. Applications to single
      pinhole and multi-pinhole imaging showed that this method greatly reduced the
      reconstruction artifacts.

PMID- 25574057
TI  - Abrogation of HMX1 function causes rare oculoauricular syndrome associated with
      congenital cataract, anterior segment dysgenesis, and retinal dystrophy.
AB  - PURPOSE: To define the phenotypic manifestation, confirm the genetic basis, and
      delineate the pathogenic mechanisms underlying an oculoauricular syndrome (OAS).
      METHODS: Two individuals from a consanguineous family underwent comprehensive
      clinical phenotyping and electrodiagnostic testing (EDT). Genome-wide microarray
      analysis and Sanger sequencing of the candidate gene were used to identify the
      likely causal variant. Protein modelling, Western blotting, and dual luciferase
      assays were used to assess the pathogenic effect of the variant in vitro.
      RESULTS: Complex developmental ocular abnormalities of congenital cataract,
      anterior segment dysgenesis, iris coloboma, early-onset retinal dystrophy, and
      abnormal external ear cartilage presented in the affected family members. Genetic
      analyses identified a homozygous c.650A>C; p.(Gln217Pro) missense mutation within
      the highly conserved homeodomain of the H6 family homeobox 1 (HMX1) gene. Protein
      modelling predicts that the variant may have a detrimental effect on protein
      folding and/or stability. In vitro analyses were able to demonstrate that the
      mutation has no effect on protein expression but adversely alters function.
      CONCLUSIONS: Oculoauricular syndrome is an autosomal recessive condition that has
      a profound effect on the development of the external ear, anterior segment, and
      retina, leading to significant visual loss at an early age. This study has
      delineated the phenotype and confirmed HMX1 as the gene causative of OAS,
      enabling the description of only the second family with the condition. HMX1 is a
      key player in ocular development, possibly in both the pathway responsible for
      lens and retina development, and via the gene network integral to optic fissure
      closure.

PMID- 25574059
TI  - "Not Designed for Us": How Science Museums and Science Centers Socially Exclude
      Low-Income, Minority Ethnic Groups.
AB  - This paper explores how people from low-income, minority ethnic groups perceive
      and experience exclusion from informal science education (ISE) institutions, such
      as museums and science centers. Drawing on qualitative data from four focus
      groups, 32 interviews, four accompanied visits to ISE institutions, and field
      notes, this paper presents an analysis of exclusion from science learning
      opportunities during visits alongside participants' attitudes, expectations, and
      conclusions about participation in ISE. Participants came from four community
      groups in central London: a Sierra Leonean group (n = 21), a Latin American group
      (n = 18), a Somali group (n = 6), and an Asian group (n = 13). Using a
      theoretical framework based on the work of Bourdieu, the analysis suggests ISE
      practices were grounded in expectations about visitors' scientific knowledge,
      language skills, and finances in ways that were problematic for participants and
      excluded them from science learning opportunities. It is argued that ISE
      practices reinforced participants preexisting sense that museums and science
      centers were "not for us." The paper concludes with a discussion of the findings
      in relation to previous research on participation in ISE and the potential for
      developing more inclusive informal science learning opportunities.

PMID- 25574060
TI  - Total synthesis of plagiochin G and derivatives as potential cancer
      chemopreventive agents.
AB  - A new and efficient total synthesis has been developed to obtain plagiochin G
      (22), a macrocyclic bisbibenzyl, and four derivatives. The key 16-membered ring
      containing biphenyl ether and biaryl units was closed via an intramolecular SNAr
      reaction. All synthesized macrocyclic bisbibenzyls inhibited Epstein-Barr virus
      early antigen (EBVEA) activation induced by the tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA) in Raji cells and, thus, are potential
      cancer chemopreventive agents.

PMID- 25574061
TI  - Finite volume hydromechanical simulation in porous media.
AB  - Cell-centered finite volume methods are prevailing in numerical simulation of
      flow in porous media. However, due to the lack of cell-centered finite volume
      methods for mechanics, coupled flow and deformation is usually treated either by
      coupled finite-volume-finite element discretizations, or within a finite element
      setting. The former approach is unfavorable as it introduces two separate grid
      structures, while the latter approach loses the advantages of finite volume
      methods for the flow equation. Recently, we proposed a cell-centered finite
      volume method for elasticity. Herein, we explore the applicability of this novel
      method to provide a compatible finite volume discretization for coupled
      hydromechanic flows in porous media. We detail in particular the issue of
      coupling terms, and show how this is naturally handled. Furthermore, we observe
      how the cell-centered finite volume framework naturally allows for modeling
      fractured and fracturing porous media through internal boundary conditions. We
      support the discussion with a set of numerical examples: the convergence
      properties of the coupled scheme are first investigated; second, we illustrate
      the practical applicability of the method both for fractured and heterogeneous
      media.

PMID- 25574062
TI  - A SIGNIFICANCE TEST FOR THE LASSO.
AB  - In the sparse linear regression setting, we consider testing the significance of
      the predictor variable that enters the current lasso model, in the sequence of
      models visited along the lasso solution path. We propose a simple test statistic
      based on lasso fitted values, called the covariance test statistic, and show that
      when the true model is linear, this statistic has an Exp(1) asymptotic
      distribution under the null hypothesis (the null being that all truly active
      variables are contained in the current lasso model). Our proof of this result for
      the special case of the first predictor to enter the model (i.e., testing for a
      single significant predictor variable against the global null) requires only weak
      assumptions on the predictor matrix X. On the other hand, our proof for a general
      step in the lasso path places further technical assumptions on X and the
      generative model, but still allows for the important high-dimensional case p > n,
      and does not necessarily require that the current lasso model achieves perfect
      recovery of the truly active variables. Of course, for testing the significance
      of an additional variable between two nested linear models, one typically uses
      the chi-squared test, comparing the drop in residual sum of squares (RSS) to a
      [Formula: see text] distribution. But when this additional variable is not fixed,
      and has been chosen adaptively or greedily, this test is no longer appropriate:
      adaptivity makes the drop in RSS stochastically much larger than [Formula: see
      text] under the null hypothesis. Our analysis explicitly accounts for adaptivity,
      as it must, since the lasso builds an adaptive sequence of linear models as the
      tuning parameter lambda decreases. In this analysis, shrinkage plays a key role:
      though additional variables are chosen adaptively, the coefficients of lasso
      active variables are shrunken due to the [Formula: see text] penalty. Therefore,
      the test statistic (which is based on lasso fitted values) is in a sense balanced
      by these two opposing properties-adaptivity and shrinkage-and its null
      distribution is tractable and asymptotically Exp(1).

PMID- 25574063
TI  - Envisioning the Third Sector's Welfare Role: Critical Discourse Analysis of 'Post
      Devolution' Public Policy in the UK 1998-2012.
AB  - Welfare state theory has struggled to come to terms with the role of the third
      sector. It has often categorized welfare states in terms of the pattern of
      interplay between state social policies and the structure of the labour market.
      Moreover, it has frequently offered an exclusive focus on state policy - thereby
      failing to substantially recognize the role of the formally organized third
      sector. This study offers a corrective view. Against the backdrop of the
      international shift to multi-level governance, it analyses the policy discourse
      of third sector involvement in welfare governance following devolution in the UK.
      It reveals the changing and contrasting ways in which post-devolution territorial
      politics envisions the sector's role as a welfare provider. The mixed methods
      analysis compares policy framing and the structural narratives associated with
      the development of the third sector across the four constituent polities of the
      UK since 1998. The findings reveal how devolution has introduced a new spatial
      policy dynamic. Whilst there are elements of continuity between polities - such
      as the increasing salience of the third sector in welfare provision - policy
      narratives also provide evidence of the territorialization of third sector
      policy. From a methodological standpoint, this underlines the distinctive and
      complementary role discourse-based analysis can play in understanding
      contemporary patterns and processes shaping welfare governance.

PMID- 25574064
TI  - The Unique Relations between Early Homelessness and Educational Well-Being: An
      Empirical Test of the Continuum of Risk Hypothesis.
AB  - This study examined the Continuum of Risk Hypothesis by assessing the unique
      relations between early homelessness and educational outcomes while controlling
      for co-occurring risks. An integrated data system was used to account for
      multiple co-occurring early risk factors for an entire cohort of first grade
      students in a large urban school district and municipality (N = 8,267).
      Multilevel linear regression models indicated that the presence of some co
      occurring risk factors explained the relation between homelessness and academic
      engagement problems in school. However, after controlling for co-occurring risks,
      an experience of homelessness was found to be uniquely related to social
      engagement problems in first grade. These results support the Continuum of Risk
      Hypothesis and stress the importance of early intervention for children with an
      experience of homelessness to foster their social development.

PMID- 25574065
TI  - Broadband 2.4 MUm superluminescent GaInAsSb/AlGaAsSb quantum well diodes for
      optical sensing of biomolecules.
AB  - High power, high radiance, broadband light sources emitting in the 2.0-2.5 MUm
      wavelength range are important for optical sensing of biomolecules such as
      glucose in aqueous solutions. Here we demonstrate and analyze superluminescent
      diodes with output centered at 2.4 MUm (range ~2.2-2.5 MUm) from
      GaInAsSb/AlGaAsSb quantum wells in a separate confinement structure. Pulsed wave
      output of 1 mW (38 kW/cm2/sr) is achieved at room temperature for 40MUm * 2mm
      devices. Superluminescence is evidenced in superlinear increase in emission,
      spectral narrowing, and angular narrowing of light output with increasing current
      injection. Optical output is analyzed and modeled with rate equations. Potential
      routes for future improvements are explored, such as additional Auger suppression
      and photonic mode engineering.

PMID- 25574066
TI  - Serum clusterin as a tumor marker and prognostic factor for patients with
      esophageal cancer.
AB  - BACKGROUND: Recent studies have revealed that clusterin is implicated in many
      physiological and pathological processes, including tumorigenesis. However, the
      relationship between serum clusterin expression and esophageal squamous cell
      carcinoma (ESCC) is unclear. METHODS: The serum clusterin concentrations of 87
      ESCC patients and 136 healthy individuals were examined. An independent-samples
      Mann-Whitney U test was used to compare serum clusterin concentrations of ESCC
      patients to those of healthy controls. Univariate analysis was conducted using
      the log-rank test and multivariate analyses were performed using the Cox
      proportional hazards model. RESULTS: In healthy controls, the mean clusterin
      concentration was 288.8 +/- 75.1 MUg/mL, while in the ESCC patients, the mean
      clusterin concentration was higher at 412.3 +/- 159.4 MUg/mL (P < 0.0001). The 1
      , 2-, and 4-year survival rates for the 87 ESCC patients were 89.70%, 80.00%, and
      54.50%. Serum clusterin had an optimal diagnostic cut-off point (serum clusterin
      concentration = 335.5 MUg/mL) for esophageal squamous cell carcinoma with
      sensitivity of 71.26% and specificity of 77.94%. And higher serum clusterin
      concentration (>500 MUg/mL) indicated better prognosis (P = 0.030). CONCLUSIONS:
      Clusterin may play a key role during tumorigenesis and tumor progression of ESCC
      and it could be applied in clinical work as a tumor marker and prognostic factor.

PMID- 25574067
TI  - Mig-6 gene knockout induces neointimal hyperplasia in the vascular smooth muscle
      cell.
AB  - Although advances in vascular interventions can reduce the mortality associated
      with cardiovascular disease, neointimal hyperplasia remains a clinically
      significant obstacle limiting the success of current interventions.
      Identification of signaling pathways involved in migration and proliferation of
      vascular smooth muscle cells (SMCs) is an important approach for the development
      of modalities to combat this disease. Herein we investigate the role of an
      immediate early response gene, mitogen-inducible gene-6 (Mig-6), in the
      development of neointimal hyperplasia using vascular smooth muscle specific Mig-6
      knockout mice. We induced endoluminal injury to one side of femoral artery by
      balloon dilatation in both Mig-6 knockout and control mice. Four weeks following
      injury, the artery of Mig-6 knockout mice demonstrated a 5.3-fold increase in the
      neointima/media ratio compared with control mice (P = 0.04). In addition, Mig-6
      knockout vascular SMCs displayed an increase in both cell migration and
      proliferation compared with wild-type SMCs. Taken together, our data suggest that
      Mig-6 plays a critical role in the development of atherosclerosis. This finding
      provides new insight into the development of more effective ways to treat and
      prevent neointimal hyperplasia, particularly in-stent restenosis after
      percutaneous vascular intervention. 

PMID- 25574069
TI  - A Comparative Analysis of the Validity of US State- and County-Level Social
      Capital Measures and Their Associations with Population Health.
AB  - The goals of this study were to validate a number of available collective social
      capital measures at the U.S. state and county levels, and to examine the relative
      extent to which these social capital measures are associated with population
      health outcomes. Measures of social capital at the U.S. state level included
      aggregate indices based on the Annenberg National Health Communication Survey
      (ANHCS) and the Behavioral Risk Factor Surveillance System (BRFSS), Petris Social
      Capital Index (PSCI), Putnam's index, and Kim et al.'s scales. County-level
      measures consisted of Rupasingha et al.'s social capital index (RGFI) and a BRFSS
      derived measure. These measures, except for the PSCI, showed evidence of
      acceptable validity. Moreover, we observed differences across the social capital
      measures in their associations with population health outcomes. The implications
      of the findings for future research in this area are discussed.

PMID- 25574070
TI  - Barriers to Seeking Mental Health Services among Adolescents in Military
      Families.
AB  - Military families with adolescents experience high levels of stress associated
      with parental deployment, but many of these families do not seek or utilize
      mental health services. The current qualitative study was designed to better
      understand barriers to mental health treatment experienced by adolescents in
      military families. Focus groups and individual interviews were conducted with
      military adolescents (n = 13), military (non-enlisted) parents (n = 12), and
      mental health service providers who treat adolescents in military families (n =
      20). Discussions primarily explored barriers to seeking treatment, with
      supplemental questions assessing the ideal elements of mental health services for
      this population. Seven barriers to engaging in mental health services were
      identified: four internal (confidentiality concerns, stigma, ethic of self
      reliance, lack of perceived relevance) and three external (time and effort
      concerns, logistical concerns, financial concerns). Challenges engaging military
      adolescents in mental health services are discussed and several recommendations
      are offered for service providers attempting to work with this population.

PMID- 25574068
TI  - Methylation of DLEC1 promoter is a predictor for recurrence in Chinese patients
      with gastric cancer.
AB  - PURPOSE: To investigate promoter methylation in the deleted in lung and
      esophageal cancer 1 (DLEC1) gene in Chinese patients with gastric cancer.
      METHODS: A total of 227 patients with gastric cancer were enrolled. The
      methylations of the promoter regions of DLEC1 and ACTB were determined using
      quantitative methylation-specific PCR. The DLEC1 methylation was compared to the
      clinicopathological variables of gastric cancer. RESULTS: DLEC1 methylation was
      not associated with the clinicopathological variables of gastric cancer. Patients
      with DLEC1-hypermethylated gastric cancer had significantly higher recurrence
      rate than those with DLEC1-hypomethylated gastric cancer (P = 0.025; hazard ratio
      = 2.43). CONCLUSIONS: Methylation of DELC1 promoter may be a valuable predictor
      for recurrence in Chinese patients with gastric cancer.

PMID- 25574071
TI  - Ubiquitous burden: the contribution of migration to AIDS and Tuberculosis
      mortality in rural South Africa.
AB  - The paper aims to estimate the extent to which migrants are contributing to AIDS
      or tuberculosis (TB) mortality among rural sub-district populations. The
      Agincourt (South Africa) health and socio-demographic surveillance system
      provided comprehensive data on vital and migration events between 1994 and 2006.
      AIDS and TB cause-deleted life expectancy, and crude death rates by gender,
      migration status and period were computed. The annualised crude death rate almost
      tripled from 5.39 [95% CI 5.13-5.65] to 15.10 [95% CI 14.62-15.59] per 1000 over
      the years 1994-2006. The contribution of AIDS and TB in returned migrants to the
      increase in crude death rate was 78.7% [95% CI 77.4-80.1] for males and 44.4%
      [95% CI 43.2-46.1] for females. So, in a typical South African setting dependent
      on labour migration for rural livelihoods, the contribution of returned migrants,
      many infected with AIDS and TB, to the burden of disease is high.

PMID- 25574072
TI  - Strategies Toward Well-Defined Polymer Nanoparticles Inspired by Nature:
      Chemistry versus Versatility.
AB  - Polymeric nanoparticles are promising delivery platforms for various biomedical
      applications. One of the main challenges toward the development of therapeutic
      nanoparticles is the premature disassembly and release of the encapsulated drug.
      Among the different strategies to enhance the kinetic stability of polymeric
      nanoparticles, shell- and core-crosslinking have been shown to provide robust
      character, while creating a suitable environment for encapsulation of a wide
      range of therapeutics, including hydrophilic, hydrophobic, metallic, and small
      and large biomolecules, with gating of their release as well. The versatility of
      shell- and core-crosslinked nanoparticles is driven from the ease by which the
      structures of the shell- and core-forming polymers and crosslinkers can be
      modified. In addition, postmodification with cell-recognition moieties, grafting
      of antibiofouling polymers, or chemical degradation of the core to yield
      nanocages allow the use of these robust nanostructures as "smart" nanocarriers.
      The building principles of these multifunctional nanoparticles borrow analogy
      from the synthesis, supramolecular assembly, stabilization, and dynamic activity
      of the naturally driven biological nanoparticles such as proteins, lipoproteins,
      and viruses. In this review, the chemistry involved during the buildup from small
      molecules to polymers to covalently stabilized nanoscopic objects is detailed,
      with contrast of the strategies of the supramolecular assembly of polymer
      building blocks followed by intramicellar stabilization into shell-, core-, or
      core-shell-crosslinked knedel-like nanoparticles versus polymerization of
      polymers into nanoscopic molecular brushes followed by further intramolecular
      covalent stabilization events. The rational design of shell-crosslinked knedel
      like nanoparticles is then elaborated for therapeutic packaging and delivery,
      with emphasis on the polymer chemistry aspects to accomplish the synthesis of
      such nanoparticulate systems.

PMID- 25574073
TI  - Model Comparison Tests to Determine Data Information Content.
AB  - In the context of inverse or parameter estimation problems we demonstrate the use
      of statistically based model comparison tests in several examples of practical
      interest. In these examples we are interested in questions related to information
      content of a particular given data set and whether the data will support a more
      complicated model to describe it. In the first example we compare fits for
      several different models to describe simple decay in a size histogram for
      aggregates in amyloid fibril formation. In a second example we investigate
      whether the information content in data sets for the pest Lygus hesperus in
      cotton fields as it is currently collected is sufficient to support a model in
      which one distinguishes between nymphs and adults. Finally in a third example
      with data for patients having undergone an organ transplant, we question whether
      the data content is sufficient to estimate more than 5 of the fundamental
      parameters in a particular dynamic model.

PMID- 25574074
TI  - Cognitive Control and Motivation.
AB  - Adolescence is associated with heightened mortality rates due in large measure to
      negative consequences from risky behaviors. Theories of adolescent risk taking
      posit that immature cognitive control coupled with heightened reward reactivity
      drive adolescent risk-taking, yet surprisingly few empirical studies have
      examined these neurobiological systems together. In this paper, we describe a
      related series of studies from our laboratory aimed at further delineating the
      maturation of cognitive control through adolescence, as well as how rewards
      influence a key aspect of cognitive control, response inhibition. Our findings
      indicate that adolescents can exert adult-like control over their behavior, but
      that they have limitations regarding the consistency with which they can generate
      optimal responses compared to adults. Moreover, we demonstrate that the brain
      circuitry supporting mature cognitive (inhibitory) control is still undergoing
      development. Our work using the rewarded antisaccade task, a paradigm that
      enables concurrent assessment of rewards and inhibitory control, indicates that
      adolescents show delayed but heightened responses in key reward regions along
      with concurrent activation in brain systems that support behaviors leading to
      reward acquisition. Considered together, our results highlight adolescent
      specific differences in the integration of basic brain processes that may
      underlie decision-making and more complex risk taking in adolescence.

PMID- 25574075
TI  - Surgery for obstructed defecation syndrome - is there an ideal technique.
AB  - Obstructive defecation syndrome (ODS) is a common disorder with a considerable
      impact on the quality of life of affected patients. Surgery for ODS remains a
      challenging topic. There exists a great variety of operative techniques to treat
      patients with ODS. According to the surgeon's preference the approach can be
      transanal, transvaginal, transperineal or transabdominal. All techniques have its
      advantages and disadvantages. Notably, high evidence based studies are
      significantly lacking in literature, thus making accurate assessments difficult.
      Careful patient's selection is crucial to achieve optimal functional results. It
      is mandatory to assess not only defecation disorders but also evaluate overall
      pelvic floor symptoms, such as fecal incontinence and urinary disorders for
      choosing an appropriate and tailored strategy. Radiological investigation is
      essential but may not explain complaints of every patient. 

PMID- 25574076
TI  - Fecal transplant policy and legislation.
AB  - Fecal microbiota transplantation (FMT) has garnered significant attention in
      recent years in the face of a reemerging Clostridium difficile (C. difficile)
      epidemic. Positive results from the first randomized control trial evaluating FMT
      have encouraged the medical community to explore the process further and expand
      its application beyond C. difficile infections and even the gastrointestinal
      domain. However promising and numerous the prospects of FMT appear, the method
      remains limited in scope today due to several important barriers, most notably a
      poorly defined federal regulatory policy. The Food and Drug Administration has
      found it difficult to standardize and regulate the administration of inherently
      variable, metabolically active, and ubiquitously available fecal material. The
      current cumbersome policy, which classifies human feces as a drug, has prevented
      physicians from providing FMT and deserving patients from accessing FMT in a
      timely fashion, and subsequent modifications seem only to be temporary. The
      argument for reclassifying fecal material as human tissue is well supported.
      Essentially, this would allow for a regulatory framework that is sufficiently
      flexible to expand access to care and facilitate research, but also appropriately
      restrictive and centralized to ensure patient safety. Such an approach can
      facilitate the advancement of FMT to a more refined, controlled, and aesthetic
      process, perhaps in the form of a customized and well-characterized stool
      substitute therapy. 

PMID- 25574077
TI  - Modern management of anal fistula.
AB  - Ideal surgical treatment for anal fistula should aim to eradicate sepsis and
      promote healing of the tract, whilst preserving the sphincters and the mechanism
      of continence. For the simple and most distal fistulae, conventional surgical
      options such as laying open of the fistula tract seem to be relatively safe and
      therefore, well accepted in clinical practise. However, for the more complex
      fistulae where a significant proportion of the anal sphincter is involved, great
      concern remains about damaging the sphincter and subsequent poor functional
      outcome, which is quite inevitable following conventional surgical treatment. For
      this reason, over the last two decades, many sphincter-preserving procedures for
      the treatment of anal fistula have been introduced with the common goal of
      minimising the injury to the anal sphincters and preserving optimal function.
      Among them, the ligation of intersphincteric fistula tract procedure appears to
      be safe and effective and may be routinely considered for complex anal fistula.
      Another technique, the anal fistula plug, derived from porcine small intestinal
      submucosa, is safe but modestly effective in long-term follow-up, with success
      rates varying from 24%-88%. The failure rate may be due to its extrusion from the
      fistula tract. To obviate that, a new designed plug (GORE BioA(r)) was
      introduced, but long term data regarding its efficacy are scant. Fibrin glue
      showed poor and variable healing rate (14%-74%). FiLaC and video-assisted anal
      fistula treatment procedures, respectively using laser and electrode energy, are
      expensive and yet to be thoroughly assessed in clinical practise. Recently, a
      therapy using autologous adipose-derived stem cells has been described. Their
      properties of regenerating tissues and suppressing inflammatory response must be
      better investigated on anal fistulae, and studies remain in progress. The aim of
      this present article is to review the pertinent literature, describing the
      advantages and limitations of new sphincter-preserving techniques. 

PMID- 25574079
TI  - Systematic mechanism-orientated approach to chronic pancreatitis pain.
AB  - Pain in chronic pancreatitis (CP) shows similarities with other visceral pain
      syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus
      be managed in a similar fashion. Typical causes of CP pain include increased
      intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic
      complications. Unfortunately, CP pain continues to be a major clinical challenge.
      It is recognized that ongoing pain may induce altered central pain processing,
      e.g., central sensitization or pro-nociceptive pain modulation. When this is
      present conventional pain treatment targeting the nociceptive focus, e.g., opioid
      analgesia or surgical/endoscopic intervention, often fails even if technically
      successful. If central nervous system pain processing is altered, specific
      treatment targeting these changes should be instituted (e.g., gabapentinoids,
      ketamine or tricyclic antidepressants). Suitable tools are now available to make
      altered central processing visible, including quantitative sensory testing,
      electroencephalograpy and (functional) magnetic resonance imaging. These
      techniques are potentially clinically useful diagnostic tools to analyze central
      pain processing and thus define optimum management approaches for pain in CP and
      other visceral pain syndromes. The present review proposes a systematic mechanism
      orientated approach to pain management in CP based on a holistic view of the
      mechanisms involved. Future research should address the circumstances under which
      central nervous system pain processing changes in CP, and how this is influenced
      by ongoing nociceptive input and therapies. Thus we hope to predict which
      patients are at risk for developing chronic pain or not responding to therapy,
      leading to improved treatment of chronic pain in CP and other visceral pain
      disorders. 

PMID- 25574081
TI  - P53 mutations in colorectal cancer - molecular pathogenesis and pharmacological
      reactivation.
AB  - Colorectal cancer (CRC) is one of the most common malignancies with high
      prevalence and low 5-year survival. CRC is a heterogeneous disease with a
      complex, genetic and biochemical background. It is now generally accepted that a
      few important intracellular signaling pathways, including Wnt/beta-catenin
      signaling, Ras signaling, and p53 signaling are frequently dysregulated in CRC.
      Patients with mutant p53 gene are often resistant to current therapies,
      conferring poor prognosis. Tumor suppressor p53 protein is a transcription factor
      inducing cell cycle arrest, senescence, and apoptosis under cellular stress.
      Emerging evidence from laboratories and clinical trials shows that some small
      molecule inhibitors exert anti-cancer effect via reactivation and restoration of
      p53 function. In this review, we summarize the p53 function and characterize its
      mutations in CRC. The involvement of p53 mutations in pathogenesis of CRC and
      their clinical impacts will be highlighted. Moreover, we also describe the
      current achievements of using p53 modulators to reactivate this pathway in CRC,
      which may have great potential as novel anti-cancer therapy.

PMID- 25574082
TI  - Radiation therapy has been shown to be adaptable for various stages of
      hepatocellular carcinoma.
AB  - In addition to surgical procedures, radiofrequency ablation is commonly used for
      the treatment of hepatocellular carcinomas (HCCs) of limited size and number.
      Transcatheter arterial chemoembolization (TACE), using iodized poppy seed oil,
      Lipiodol and anticancer drugs, has been actively performed for the treatment of
      unresectable HCC, particularly in Asian countries. Recently, Sorafenib become
      available for advanced HCCs when the liver is still sufficiently functional.
      Sorafenib is an oral multikinase inhibitor with antiproliferative and
      antiangiogenic effects. However, the effect of sorafenib seems to be inadequate
      to control the progression of HCC. Radiation therapy (RT) for HCC has a potential
      role across all stages of HCC. However, RT is generally not considered an option
      in HCC consensus documents or national guidelines, primarily because of
      insufficient supporting evidence. However, the method of RT has much improved
      because of advances in technology. Moreover, combined treatment of RT plus other
      treatments (TACE, sorafenib and chemotherapy etc.) has become one of the
      alternative therapies for HCC. Therefore, we should understand the various kinds
      of RT available for HCC. In this review, we focus on various kinds of external
      beam radiation therapy. 

PMID- 25574078
TI  - Differential diagnosis in inflammatory bowel disease colitis: state of the art
      and future perspectives.
AB  - Distinction between Crohn's disease of the colon-rectum and ulcerative colitis or
      inflammatory bowel disease (IBD) type unclassified can be of pivotal importance
      for a tailored clinical management, as each entity often involves specific
      therapeutic strategies and prognosis. Nonetheless, no gold standard is available
      and the uncertainty of diagnosis may frequently lead to misclassification or
      repeated examinations. Hence, we have performed a literature search to address
      the problem of differential diagnosis in IBD colitis, revised current and
      emerging diagnostic tools and refined disease classification strategies.
      Nowadays, the differential diagnosis is an untangled issue, and the proper
      diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis.
      This topic is receiving emerging attention, as medical therapies, surgical
      approaches and leading prognostic outcomes require more and more disease-specific
      strategies in IBD patients. The optimization of standard diagnostic approaches
      based on clinical features, biomarkers, radiology, endoscopy and histopathology
      appears to provide only marginal benefits. Conversely, emerging diagnostic
      techniques in the field of gastrointestinal endoscopy, molecular pathology,
      genetics, epigenetics, metabolomics and proteomics have already shown promising
      results. Novel advanced endoscopic imaging techniques and biomarkers can shed new
      light for the differential diagnosis of IBD, better reflecting diverse disease
      behaviors based on specific pathogenic pathways.

PMID- 25574080
TI  - Autoimmune hepatitis, one disease with many faces: etiopathogenetic, clinico
      laboratory and histological characteristics.
AB  - Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown
      etiology characterized by hypergammaglobulinemia, autoantibodies detection and
      interface hepatitis. Due to the absence of specific diagnostic markers and the
      large heterogeneity of its clinical, laboratory and histological features, AIH
      diagnosis may be potentially difficult. Therefore, in this in-depth review we
      summarize the substantial progress on etiopathogenesis, clinical, serological and
      histological phenotypes of AIH. AIH has a global distribution affecting any age,
      both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic
      to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective
      elevation of IgG is found in most cases. Autoimmune attack is perpetuated,
      possibly via molecular mimicry, and favored by the impaired control of T
      regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic
      rosette formation) and autoantibodies detection although not pathognomonic, are
      still the hallmark for a timely diagnosis. AIH remains a major diagnostic
      challenge. AIH should be considered in every case in the absence of viral,
      metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory
      personnel, hepato-pathologists and clinicians need to become more familiar with
      disease expressions and the interpretation of liver histology and autoimmune
      serology to derive maximum benefit for the patient. 

PMID- 25574086
TI  - Extent of surgery in cancer of the colon: is more better?
AB  - Since the introduction of total mesorectal excision as the standard approach in
      mid and low rectal cancer, the incidence of local recurrence has sharply
      declined. Similar attention to surgical technique in colon cancer (CC) has
      resulted in the concept of complete mesocolic excision (CME), which consists of
      complete removal of the intact mesentery and high ligation of the vascular supply
      at its origin. Although renewed attention to meticulous surgical technique
      certainly has its merits, routine implementation of CME is currently unfounded.
      Firstly, in contrast to rectal cancer, local recurrence originating from an
      incompletely removed mesentery is rare in CC and usually a manifestation of
      systemic disease. Secondly, although CME may increase nodal counts and therefore
      staging accuracy, this is unlikely to affect survival since the observed
      relationship between nodal counts and outcome in CC is most probably not causal
      but confounded by a range of clinical variables. Thirdly, several lines of
      evidence suggest that metastasis to locoregional nodes occurs early and is a
      stochastic rather than a stepwise phenomenon in CC, in essence reflecting the
      tumor-host-metastasis relationship. Unsurprisingly, therefore, comparative
      studies in CC as well as in other digestive cancers have failed to demonstrate
      any survival benefit associated with extensive, additional or extra-mesenteric
      lymphadenectomy. Finally, routine implementation of CME may cause patient harm by
      longer operating times, major vascular damage and autonomic nerve injury.
      Therefore, data from randomized trials reporting relevant endpoints are required
      before CME can be recommended as a standard approach in CC surgery. 

PMID- 25574084
TI  - Stem cells in gastric cancer.
AB  - Gastric cancer (GC) is one of the leading causes of cancer-related mortality
      worldwide. Cancer stem cells (CSCs), which were first identified in acute myeloid
      leukemia and subsequently in a large array of solid tumors, play important roles
      in cancer initiation, dissemination and recurrence. CSCs are often transformed
      tissue-specific stem cells or de-differentiated transit amplifying progenitor
      cells. Several populations of multipotent gastric stem cells (GSCs) that reside
      in the stomach have been determined to regulate physiological tissue renewal and
      injury repair. These populations include the Villin+ and Lgr5+ GSCs in the
      antrum, the Troy+ chief cells in the corpus, and the Sox2+ GSCs that are found in
      both the antrum and the corpus. The disruption of tumor suppressors in Villin+ or
      Lgr5+ GSCs leads to GC in mouse models. In addition to residing GSCs, bone marrow
      derived cells can initiate GC in a mouse model of chronic Helicobacter infection.
      Furthermore, expression of the cell surface markers CD133 or CD44 defines gastric
      CSCs in mouse models and in human primary GC tissues and cell lines. Targeted
      elimination of CSCs effectively reduces tumor size and grade in mouse models. In
      summary, the recent identification of normal GSCs and gastric CSCs has greatly
      improved our understanding of the molecular and cellular etiology of GC and will
      aid in the development of effective therapies to treat patients.

PMID- 25574083
TI  - Fecal microbiota transplantation broadening its application beyond intestinal
      disorders.
AB  - Intestinal dysbiosis is now known to be a complication in a myriad of diseases.
      Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is
      arguably very effective for curing Clostridium difficile infection and has good
      outcomes in other intestinal diseases. New insights have raised an interest in
      FMT for the management of extra-intestinal disorders associated with gut
      microbiota. This review shows that it is an exciting time in the burgeoning
      science of FMT application in previously unexpected areas, including metabolic
      diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders,
      and tumors. A randomized controlled trial was conducted on FMT in metabolic
      syndrome by infusing microbiota from lean donors or from self-collected feces,
      with the resultant findings showing that the lean donor feces group displayed
      increased insulin sensitivity, along with increased levels of butyrate-producing
      intestinal microbiota. Case reports of FMT have also shown favorable outcomes in
      Parkinson's disease, multiple sclerosis, myoclonus dystonia, chronic fatigue
      syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in
      the manipulation of the intestinal microbiota and has potential applications in a
      variety of extra-intestinal conditions associated with intestinal dysbiosis. 

PMID- 25574085
TI  - Review of the treatment of liver hydatid cysts.
AB  - A review was carried out in Medline, LILACS and the Cochrane Library. Our
      database search strategy included the following terms: "hydatid cyst", "liver",
      "management", "meta-analysis" and "randomized controlled trial". No language
      limits were used in the literature search. The latest electronic search date was
      the 7(th) of January 2014. INCLUSION AND EXCLUSION CRITERIA: all relevant studies
      on the assessment of therapeutic methods for hydatid cysts of the liver were
      considered for analysis. Information from editorials, letters to publishers, low
      quality review articles and studies done on animals were excluded from analysis.
      Additionally, well-structured abstracts from relevant articles were selected and
      accepted for analysis. Standardized forms were designed for data extraction; two
      investigators entered the data on patient demographics, methodology, recurrence
      of HC, mean cyst size and number of cysts per group. Four hundred and fourteen
      articles were identified using the previously described search strategy. After
      applying the inclusion and exclusion criteria detailed above, 57 articles were
      selected for final analysis: one meta-analysis, 9 randomized clinical trials, 5
      non-randomized comparative prospective studies, 7 non-comparative prospective
      studies, and 34 retrospective studies (12 comparative and 22 non-comparative).
      Our results indicate that antihelminthic treatment alone is not the ideal
      treatment for liver hydatid cysts. More studies in the literature support the
      effectiveness of radical treatment compared with conservative treatment.
      Conservative surgery with omentoplasty is effective in preventing postoperative
      complications. A laparoscopic approach is safe in some situations. Percutaneous
      drainage with albendazole therapy is a safe and effective alternative treatment
      for hydatid cysts of the liver. Radical surgery with pre- and post-operative
      administration of albendazole is the best treatment option for liver hydatid
      cysts due to low recurrence and complication rates.

PMID- 25574087
TI  - Pharmacological therapy used in the elimination of Helicobacter pylori infection:
      a review.
AB  - The optimal therapy for Helicobacter pylori (H. pylori) infection should combine
      a high cure rate and a short treatment duration with a favorable side-effect
      profile and should maintain a low cost. Several strategies have been proposed to
      increase the H. pylori eradication rate, including the extension of the treatment
      duration to 14 d, the use of a four-drug regimen (quadruple, sequential, and
      concomitant treatments), and the use of novel antibiotics, such as levofloxacin.
      However, triple therapy remains the most widely accepted first-line treatment
      regimen in Brazil and the United States and throughout Europe. Because this
      therapy is limited by resistance to clarithromycin, other therapeutic regimens
      have been investigated worldwide. This review describes the current literature
      involving studies directly comparing these different therapies and their
      efficacies. 

PMID- 25574088
TI  - Altered vasoactive intestinal peptides expression in irritable bowel syndrome
      patients and rats with trinitrobenzene sulfonic acid-induced colitis.
AB  - AIM: To investigate the vasoactive intestinal peptides (VIP) expression in
      irritable bowel syndrome (IBS) and trinitrobenzene sulfonic acid (TNBS) induced
      colitis. METHODS: The VIP gene expression and protein plasma levels were measured
      in adult participants (45.8% male) who met Rome III criteria for IBS for longer
      than 6 mo and in a rat model of colitis as induced by TNBS. Plasma and colons
      were collected from naive and inflamed rats. Markers assessing inflammation
      (i.e., weight changes and myeloperoxidase levels) were assessed on days 2, 7, 14
      and 28 and compared to controls. Visceral hypersensitivity of the rats was
      assessed with colo-rectal distension and mechanical threshold testing on hind
      paws. IBS patients (n = 12) were age, gender, race, and BMI-matched with healthy
      controls (n = 12). Peripheral whole blood and plasma from fasting participants
      was collected and VIP plasma levels were assayed using a VIP peptide-enzyme
      immunoassay. Human gene expression of VIP was analyzed using a custom PCR array.
      RESULTS: TNBS induced colitis in the rats was confirmed with weight loss (13.7 +/
      3.2 g) and increased myeloperoxidase activity. Visceral hypersensitivity to colo
      rectal distension was increased in TNBS treated rats up to 21 d and resolved by
      day 28. Somatic hypersensitivity was also increased up to 14 d post TNBS
      induction of colitis. The expression of an inflammatory marker myeloperoxidase
      was significantly elevated in the intracellular granules of neutrophils in rat
      models following TNBS treatment compared to naive rats. This confirmed the
      induction of inflammation in rats following TNBS treatment. VIP plasma
      concentration was significantly increased in rats following TNBS treatment as
      compared to naive animals (P < 0.05). Likewise, the VIP gene expression from
      peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients
      when compared to controls (P < 0.00001; 95%CI). VIP plasma protein was not
      significantly different when compared with controls (P = 0.193). CONCLUSION:
      Alterations in VIP expression may play a role in IBS. Therefore, a better
      understanding of the physiology of VIP could lead to new therapeutics.

PMID- 25574090
TI  - Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory
      drug-induced mucosal damage in the murine small intestine.
AB  - AIM: To investigate the effect of a fat rich diet on non-steroidal anti
      inflammatory drug (NSAID)-induced mucosal damage in the murine small intestine.
      METHODS: C57BL6 mice were fed 4 types of diets with or without indomethacin. One
      group was fed standard laboratory chow. The other groups were fed a fat diet
      consisting of 8% w/w fat, beef tallow (rich in SFA), fish oil, (rich in omega-3
      PUFA), or safflower oil (rich in omega-6 PUFA). Indomethacin (3 mg/kg) was
      injected intraperitoneally from day 8 to day 10. On day 11, intestines and
      adhesions to submucosal microvessels were examined. RESULTS: In the indomethacin
      treated groups, mucosal damage was exacerbated by diets containing beef tallow
      and fish oil, and was accompanied by leukocyte infiltration (P < 0.05). The
      mucosal damage induced by indomethacin was significantly lower in mice fed the
      safflower oil diet than in mice fed the beef tallow or fish oil diet (P < 0.05).
      Indomethacin increased monocyte and platelet migration to the intestinal mucosa,
      whereas safflower oil significantly decreased monocyte and platelet recruitment
      (P < 0.05). CONCLUSION: A diet rich in SFA and omega-3 PUFA exacerbated NSAID
      induced small intestinal damage via increased leukocyte infiltration.
      Importantly, a diet rich in omega-6-PUFA did not aggravate inflammation as
      monocyte migration was blocked.

PMID- 25574089
TI  - Establishment and characterization of cell lines from chromosomal instable
      colorectal cancer.
AB  - AIM: To generate novel tumor models for preclinical validation of biomarkers that
      allow drug response prediction and individual therapeutic decisions. METHODS:
      Cell line establishment was conducted by both direct in vitro culturing and in
      vivo xenografting followed by in vitro culturing procedure. A comprehensive
      characterization was subsequently performed. This included quality control,
      consisting of the confirmation of human and colorectal cancer (CRC) origin by DNA
      fingerprint and epithelial cell adhesion molecule (EpCAM) staining, as well as
      mycoplasma and human virus testing. Phenotypic analysis was done by light
      microscopy and multicolor flow cytometry. Histopathological examination (beta
      catenin and cytokeratin staining) was conducted in direct comparison to parental
      tumor tissues. Extensive molecular-pathological profiling included mutation
      analysis for CRC-associated driver mutations, assessment of chromosomal and
      microsatellite instability, and the grade of CpG island methylation.
      Additionally, an array-based comparative genomic hybridization analysis was
      performed. Drug responsiveness was assessed for a panel of classical and novel
      substances in clinical use for the treatment of solid cancers. Finally,
      tumorigenicity of the cell lines was tested by xenografting into
      immunocompromised nude mice. RESULTS: Herein we describe the establishment of
      three ultra-low passage cell lines from two individual patients suffering from
      sporadic CRC. One cell line was derived directly from an early stage case
      (HROC18), whereas two cell lines could be established both direct from patient
      material and after xenografting from a late stage tumor (HROC32). All cell lines
      were free of contaminating mycoplasma and viruses. Molecular-pathological
      analysis allowed all cell lines to be classified as chromosomal instable
      (CIN(+)). They were aneuploid, with CpG island promoter methylation and
      microsatellite instability being absent. The following mutational profile was
      observed both in the cell lines and the parental tumor tissue: HROC18: APC(mut),
      p53(mut), K-ras(wt); HROC32: APC(wt), p53(mut), K-ras(mut). All cell lines were
      characterized as epithelial (EpCAM(+)) cells, showing distinct morphology and
      migration speed, but comparable growth kinetics. The cell lines showed different
      patterns of response towards clinically approved and novel drugs, with HROC18
      being more resistant than HROC32 cells. Finally, in vivo tumorigenicity was
      demonstrated. CONCLUSION: We successfully established and characterized novel
      ultra-low passage patient-derived CRC models as useful instruments for analyzing
      biological characteristics associated with the CIN(+) phenotype.

PMID- 25574091
TI  - Enterocyte dendritic cell-specific intercellular adhesion molecule-3-grabbing non
      integrin expression in inflammatory bowel disease.
AB  - AIM: To investigate dendritic cell-specific intercellular adhesion molecule-3
      grabbing non-integrin (DC-SIGN) expression in intestinal epithelial cells (IECs)
      in inflammatory bowel disease (IBD). METHODS: The expression of DC-SIGN in IECs
      was examined by immunohistochemistry of intestinal mucosal biopsies from 32
      patients with IBD and 10 controls. Disease activity indices and histopathology
      scores were used to assess the tissue lesions and pathologic damage. Animal
      studies utilized BALB/c mice with dextran sodium sulfate (DSS)-induced colitis
      treated with anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb).
      Controls, untreated and treated mice were sacrificed after 7 d, followed by
      isolation of colon tissue and IECs. Colonic expression of DC-SIGN, CD80, CD86 and
      MHC II was examined by immunohistochemistry or flow cytometry. The capacity of
      mouse enterocytes or dendritic cells to activate T cells was determined by co
      culture with naive CD4(+) T cells. Culture supernatant and intracellular levels
      of interleukin (IL)-4 and interferon (IFN)-gamma were measured by enzyme-linked
      immunosorbent assay and flow cytometry, respectively. The ability of IECs to
      promote T cell proliferation was detected by flow cytometry staining with
      carboxyfluorescein diacetate succinimidyl ester. RESULTS: Compared with controls,
      DC-SIGN expression was significantly increased in IECs from patients with Crohn's
      disease (P < 0.01) or ulcerative colitis (P < 0.05). DC-SIGN expression was
      strongly correlated with disease severity in IBD (r = 0.48; P < 0.05). Similarly,
      in the DSS-induced colitis mouse model, IECs showed upregulated expression of DC
      SIGN, CD80, CD86 and MHC, and DC-SIGN expression was positively correlated with
      disease activity (r = 0.62: P < 0.01). IECs from mouse colitis stimulated naive T
      cells to generate IL-4 (P < 0.05). Otherwise, dendritic cells promoted a T-helper
      1-skewing phenotype by stimulating IFN-gamma secretion. However, DC-SIGN
      expression and T cell differentiation were suppressed following treatment of mice
      with DSS-induced colitis with PsL-EGFmAb. The proliferation cycles of CD4(+) T
      cells from mice with DSS-induced colitis appeared as five cycles, which was more
      than in the control and treated groups. These results suggest that IECs can
      promote T cell proliferation. CONCLUSION: IECs regulate tissue-associated immune
      compartments under the control of DC-SIGN in IBD.

PMID- 25574093
TI  - Monochromatic energy computed tomography image for active intestinal hemorrhage:
      a model investigation.
AB  - AIM: To investigate the value of computed tomography (CT) spectral imaging in the
      evaluation of intestinal hemorrhage. METHODS: Seven blood flow rates were
      simulated in vitro. Energy spectral CT and mixed-energy CT scans were performed
      for each rate (0.5, 0.4, 0.3, 0.2, 0.1, 0.05 and 0.025 mL/min). The detection
      rates and the contrast-to-noise ratios (CNRs) of the contrast agent extravasation
      regions were compared between the two scanning methods in the arterial phase (AP)
      and the portal venous phase (PVP). Comparisons of the CNR values between the PVP
      and the AP were made for each energy level and carried out using a completely
      random t test. A chi (2) test was used to compare the detection rates obtained
      from the two scanning methods. RESULTS: The total detection rates for energy
      spectral CT and mixed-energy CT in the AP were 88.57% (31/35) and 65.71% (23/35),
      respectively, and the difference was significant (chi (2) = 5.185, P = 0.023);
      the total detection rates in the PVP were 100.00% (35/35) and 91.4% (32/35),
      respectively, and the difference was not significant (chi (2) = 1.393, P =
      0.238). In the AP, the CNR of the contrast agent extravasation regions was 3.58
      +/- 2.09 on the mixed-energy CT images, but the CNRs were 8.78 +/- 7.21 and 8.83
      +/- 6.75 at 50 and 60 keV, respectively, on the single-energy CT images, which
      were significantly different (3.58 +/- 2.09 vs 8.78 +/- 7.21, P = 0.031; 3.58 +/-
      2.09 vs 8.83 +/- 6.75, P = 0.029). In the PVP, the differences between the CNRs
      at 40, 50 and 60 keV different monochromatic energy levels and the polychromatic
      energy images were significant (19.35 +/- 10.89 vs 11.68 +/- 6.38, P = 0.010;
      20.82 +/- 11.26 vs 11.68 +/- 6.38, P = 0.001; 20.63 +/- 10.07 vs 11.68 +/- 6.38,
      P = 0.001). The CNRs at the different energy levels in the AP and the PVP were
      significantly different (t = -2.415, -2.380, -2.575, -2.762, -2.945, -3.157, 
      3.996 and -3.189). CONCLUSION: Monochromatic energy imaging spectral CT is
      superior to polychromatic energy images for the detection of intestinal
      hemorrhage, and the detection was easier in the PVP compared with the AP.

PMID- 25574092
TI  - FoxM1 overexpression promotes epithelial-mesenchymal transition and metastasis of
      hepatocellular carcinoma.
AB  - AIM: To investigate the expression of forkhead box protein M1 (FoxM1) in the
      process of epithelial mesenchymal transition in hepatocellular carcinoma (HCC)
      and its role in metastasis. METHODS: FoxM1 and E-cadherin expression in HCC
      tissue microarray specimens was evaluated by immunohistochemical staining, and
      statistical methods were applied to analyze the correlation between FoxM1 and
      epithelial-mesenchymal transition (EMT). Kaplan-Meier analysis of the correlation
      between the FoxM1 expression level and recurrence or overall survival of HCC
      patients was performed. The expression of FoxM1, E-cadherin and snail homologue 1
      (SNAI1) in HCC cell lines was evaluated by real-time reverse transcription
      polymerase chain reaction and Western blot. Hepatocyte growth factor (HGF) was
      used to induce EMT and stimulate cell migration in HCC cells. The expression of
      FoxM1 and SNAI1 was regulated by transfection with plasmids pcDNA3.1 and siRNAs
      in vitro. The occurrence of EMT was evaluated by Transwell assay, morphologic
      analysis and detection of the expression of EMT markers (E-cadherin and
      vimentin). Luciferase and chromatin immunoprecipitation assays were used to
      evaluate whether SNAI1 is a direct transcriptional target of FoxM1. RESULTS:
      FoxM1 expression was increased significantly in HCC compared with para-carcinoma
      (10.7 +/- 0.9 vs 8.2 +/- 0.7, P < 0.05) and normal hepatic (10.7 +/- 0.9 vs 2.7
      +/- 0.4, P < 0.05) tissues. Overexpression of FoxM1 was correlated with HCC tumor
      size, tumor number, macrovascular invasion and higher TNM stage, but was
      negatively correlated with E-cadherin expression in microarray specimens and in
      cell lines. FoxM1 overexpression was correlated significantly with HCC metastasis
      and EMT. In vitro, we found that FoxM1 plays a key role in HGF-induced EMT, and
      overexpression of FoxM1 could suppress E-cadherin expression and induce EMT
      changes, which were associated with increased HCC cell invasiveness. Next, we
      confirmed that FOXM1 directly binds to and activates the SNAI1 promoter, and we
      identified SNAI1 as a direct transcriptional target of FOXM1. Moreover,
      inhibiting the expression of SNAI1 significantly inhibited FoxM1-mediated EMT.
      CONCLUSION: FoxM1 overexpression promotes EMT and metastasis of HCC, and SNAI1
      plays a critical role in FoxM1-mediated EMT.

PMID- 25574094
TI  - Reactivity against microsatellite instability-induced frameshift mutations in
      patients with inflammatory bowel disease.
AB  - AIM: To analyze the cellular immune response towards microsatellite-instability
      (MSI)-induced frameshift-peptides (FSPs) in patients suffering from inflammatory
      bowel disease (IBD) with and without thiopurine-based immunosuppressive
      treatment. METHODS: Frequencies of peripheral blood T cell responses of IBD
      patients (n = 75) against FSPs derived from 14 microsatellite-containing
      candidate genes were quantified by interferon-gamma enzyme-linked immunospot. T
      cells derived from 20 healthy individuals served as controls. RESULTS:
      Significant T cell reactivities against MSI-induced FSPs were observed in 59 of
      75 IBD patients (78.7%). This was significantly more as we could observe in 20
      healthy controls (P = 0.001). Overall, the reactivity was significantly
      influenced by thiopurine treatment (P = 0.032) and duration of disease (P =
      0.002) but not by duration or cumulative amount of thiopurine therapy (P =
      0.476). Unexpected, 15 of 24 (62.5%) IBD patients without prior thiopurine
      treatment also showed increased FSP-specific immune responses (P = 0.001).
      CONCLUSION: These findings propose FSPs as potential novel class of inflammation
      associated antigens and this in turn may have implications for screening,
      diagnosis as well as clinical management of patients suffering from IBD and other
      inflammatory conditions.

PMID- 25574095
TI  - Frequency and associated factors of hair loss among patients with inflammatory
      bowel disease.
AB  - AIM: To identify the frequency of hair loss among patients with inflammatory
      bowel disease (IBD) and associated clinical and disease related factors. METHODS:
      We performed a cross sectional study in a tertiary referral adult IBD clinic.
      Self-reported history and characteristics of hair loss as well as clinical and
      demographic information were collected. Data were analyzed using univariate and
      multivariate analyses. RESULTS: Two hundred and ten consecutive IBD patients were
      recruited; one hundred and fifty patients met predefined inclusion and exclusion
      criteria. Thirty-three percent of patients reported a history of hair loss. Age,
      gender, IBD type and disease duration were not associated with hair loss. Hair
      loss was reported less frequently among patients with use of mesalamine (54% vs
      73%, P = 0.03) and anti-tumor necrosis factor medications (anti-TNF) (14% vs 40%,
      P = 0.001). In multivariate analyses adjusting for gender, IBD type and duration
      of disease, these associations with mesalamine and anti-TNF remained significant
      [(adjusted values for mesalamine (OR = 0.43, 95%CI: 0.19-0.86) and anti-TNFs (OR
      = 0.28, 95%CI: 0.08-0.98)]. CONCLUSION: Hair loss is common among patients with
      IBD. Mesalamine and anti-TNF medications were associated with lower odds of hair
      loss. Further studies are required to assess the mechanism of hair loss among
      patients with IBD.

PMID- 25574096
TI  - Interferon therapy in hepatitis C leading to chronic type 1 diabetes.
AB  - AIM: To review the prevalence, clinical data and course of interferon- associated
      type 1 diabetes in chronic hepatitis C virus (HCV) infection. METHODS: Search of
      all interferon (INF)-related type 1 diabetes mellitus (T1DM) cases published in
      the English literature from 1992 to December 2013 according to the key words:
      chronic hepatitis C infection, diabetes mellitus type 1, insulin dependent
      diabetes mellitus, and interferon treatment. We found 107 cases and analyzed
      their clinical and laboratory data and long-term follow-up. Due to the
      predominance of cases described in Japanese literature, we analyzed separately
      cases of Caucasian and Japanese origin. In addition we describe a representative
      case with HCV who developed INF-related T1DM. RESULTS: Our data show that INF
      treatment increases the risk of developing T1DM by 10-18 fold compared with the
      corresponding general population and the median age of onset was 43 years (range:
      24-66 years) in Caucasians and 52 years (range: 45-63 years) in Japanese. Most
      patients developed T1DM during INF treatment, after a median time-period of 4.2
      and 5.7 mo in Caucasian and Japanese groups, respectively. The clinical course
      was characterized by a fulminant course with abrupt severe hyperglycemia or
      ketoacidosis, a high titer of anti-islet autoantibodies and almost all patients
      (105/107) permanently required insulin therapy with a follow-up of up to 4 years.
      A substantial number of patients had evidence for other autoimmune disorders
      mainly thyroid diseases (25% and 31% in Caucasian and Japanese groups,
      respectively). CONCLUSION: INF-associated T1DM in HCV has a fulminant course,
      often associated with other autoimmune diseases, and results almost inevitably in
      permanent insulin therapy requirement.

PMID- 25574097
TI  - Helicobacter pylori infection in patients with selective immunoglobulin E
      deficiency.
AB  - AIM: To investigate the prevalence and clinical characteristics of Helicobacter
      pylori (H. pylori)-infected dyspeptic patients with selective immunoglobulin E
      deficiency (IgEd). METHODS: All individuals who underwent serum total
      immunoglobulin E (IgE) measurement at the Leumit Healthcare Services (Israel) in
      2012 were identified in an electronic database search (n = 18487). From these,
      selected case group subjects were >= 12 years of age and had serum total IgE < 2
      kIU/L (n = 158). The control group was selected from a random sampling of the
      remaining subjects >= 12 years of age to obtain a case-control ratio of 1:20 (n =
      3160). Dyspeptic diseases, diagnosed no more than 5 years before serum total IgE
      testing, were identified and retrieved from the electronic database using
      specific International Classification of Diseases diagnostic codes. Results of
      C(13)-urea breath tests were used to identify subjects infected with H. pylori.
      Categorical variables between case and control subjects were analyzed using
      Fisher's exact tests, whereas continuous variables were analyzed using chi (2)
      tests. RESULTS: Dyspepsia was present in 27.2% (43/158) of case subjects and
      22.7% (718/3160) of controls. Of these, significantly more case subjects (32/43,
      74.4%) than controls (223/718, 31.1%) were positive for H. pylori (P < 0.01).
      Esophagogastroduodenoscopy was performed in 19 case and 94 control subjects,
      revealing that gastritis was more prevalent in IgEd case subjects than in
      controls (57.9% vs 29.8%, P < 0.05). Furthermore, a significantly greater
      proportion of case subjects presented with peptic duodenal ulcers (63.2% vs
      15.9%, P < 0.01). Histopathologic examination showed marked chronic inflammation,
      lymphoid follicle formation and prominent germinal centers, with
      polymorphonuclear cell infiltration of gastric glands, that was similar in case
      and control biopsy tissues. Finally, IgEd case subjects that underwent
      esophagogastroduodenoscopy were more likely to exhibit treatment-refractory H.
      pylori infections that require second-line triple antibiotic therapy (47.4% vs
      11.7%, P < 0.01). CONCLUSION: IgEd is associated with higher rates of H. pylori
      associated gastritis and peptic duodenal ulcers.

PMID- 25574098
TI  - Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein
      tumor thrombosis.
AB  - AIM: To analyze hepatocellular carcinoma (HCC) patients with portal vein tumor
      thrombosis (PVTT) using the tumor-node-metastasis (TNM) staging system. METHODS:
      We retrospectively analyzed 372 patients with HCC who underwent hepatectomy
      between 1980 and 2009. We studied the outcomes of HCC patients with PVTT to
      evaluate the American Joint Committee on Cancer TNM staging system (7(th)
      edition) for stratifying and predicting the prognosis of a large cohort of HCC
      patients after hepatectomy in a single-center. Portal vein invasion (vp) 1 was
      defined as an invasion or tumor thrombus distal to the second branch of the
      portal vein, vp2 as an invasion or tumor thrombus in the second branch of the
      portal vein, vp3 as an invasion or tumor thrombus in the first branch of the
      portal vein, and vp4 as an invasion or tumor thrombus in the portal trunk or
      extending to a branch on the contralateral side. RESULTS: The cumulative 5-year
      overall survival (5yrOS) and 5-year disease-free survival (5yrDFS) rates of the
      372 patients were 58.3% and 31.3%, respectively. The 5yrDFS and 5yrOS of vp3-4
      patients (n = 10) were 20.0%, and 30.0%, respectively, which was comparable with
      the corresponding survival rates of vp1-2 patients (P = 0.466 and 0.586,
      respectively). In the subgroup analysis of patients with macroscopic PVTT (vp2
      4), the OS of the patients who underwent preoperative transarterial
      chemoembolization was comparable to that of patients who did not (P = 0.747).
      There was a significant difference in the DFS between patients with stage I HCC
      and those with stage II HCC (5yrDFS 39.2% vs 23.1%, P < 0.001); however, the DFS
      for stage II was similar to that for stage III (5yrDFS 23.1% vs 13.8%, P =
      0.330). In the subgroup analysis of stage II-III HCC (n = 148), only alpha
      fetoprotein (AFP) > 100 mg/dL was independently associated with DFS. CONCLUSION:
      Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for
      vp1-2. AFP stratified the stage II-III HCC patients according to prognosis.

PMID- 25574099
TI  - Azathioprine is essential following cyclosporine for patients with steroid
      refractory ulcerative colitis.
AB  - AIM: To evaluate long-term prognosis following cyclosporine treatment by
      examining the rate of surgery avoidance among cyclosporine responders. METHODS:
      We retrospectively reviewed clinical records for 29 patients diagnosed with
      severe steroid-refractory ulcerative colitis in our hospital from August 1997 to
      August 2008 and treated with cyclosporine by continuous intravenous infusion. All
      patients were treated with intravenous corticosteroids for more than 5 d prior to
      cyclosporine therapy. Administration was continued for up to 21 d under serum
      monitoring to maintain cyclosporine levels between 400 and 600 ng/mL. Clinical
      activity was assessed before and after cyclosporine therapy using the clinical
      activity index score, with a reduction of >= 5 considered to indicate a response.
      Among responders, we defined cases not requiring surgery for more than 5 years as
      exhibiting long-term efficacy of cyclosporine. Factors considered to be possibly
      predictive of long-term efficacy of cyclosporine were sex, age, disease duration,
      clinical activity index score, C-reactive protein level, hemoglobin level,
      disease extent, endoscopic findings, and clinical course. RESULTS: Cyclosporine
      was not discontinued due to side effects in any patient. Nineteen (65.5%) of 29
      patients were considered responders. A statistically significant (P = 0.004)
      inverse association was observed between an endoscopic finding of "mucosal
      bleeding" and responsive cases. Fifteen (9 males, 6 females) of these 19 patients
      were followed for 5 years or more, of whom 9 (60%) exhibited long-term efficacy
      of cyclosporine. Of the 10 non-responders, 9 (90%) underwent surgery within 6 mo
      of cyclosporine therapy. None of the following factors had a significant impact
      on the long-term efficacy of cyclosporine: sex, age, duration of disease,
      clinical activity index score, C-reactive protein level, hemoglobin level, extent
      of disease, endoscopic findings, or clinical course. In contrast, a significant
      association was observed for maintenance therapy with azathioprine after
      cyclosporine therapy (P = 0.0014). CONCLUSION: Maintenance therapy with
      azathioprine might improve the long-term efficacy of continuously infused
      cyclosporine for severe steroid-refractory ulcerative colitis patients.

PMID- 25574100
TI  - Long-term survival after resection of pancreatic cancer: a single-center
      retrospective analysis.
AB  - AIM: To retrospectively analyze factors affecting the long-term survival of
      patients with pancreatic cancer who underwent pancreatic resection. METHODS: From
      January 2000 to December 2011, 195 patients underwent pancreatic resection in our
      hospital. The prognostic factors after pancreatic resection were analyzed in all
      195 patients. After excluding the censored cases within an observational period,
      the clinicopathological characteristics of 20 patients who survived >= 5 (n = 20)
      and < 5 (n = 76) years were compared. For this comparison, we analyzed the
      patients who underwent surgery before June 2008 and were observed for more than 5
      years. For statistical analyses, the log-rank test was used to compare the
      cumulative survival rates, and the chi (2) and Mann-Whitney tests were used to
      compare the two groups. The Cox-Hazard model was used for a multivariate
      analysis, and P values less than 0.05 were considered significant. A multivariate
      analysis was conducted on the factors that were significant in the univariate
      analysis. RESULTS: The median survival for all patients was 27.1 months, and the
      5-year actuarial survival rate was 34.5%. The median observational period was 595
      d. With the univariate analysis, the UICC stage was significantly associated with
      survival time, and the CA19-9 <= 200 U/mL, DUPAN-2 <= 180 U/mL, tumor size <= 20
      mm, R0 resection, absence of lymph node metastasis, absence of extrapancreatic
      neural invasion, and absence of portal invasion were favorable prognostic
      factors. The multivariate analysis showed that tumor size <= 20 mm (HR = 0.40;
      95%CI: 0.17-0.83, P = 0.012) and negative surgical margins (R0 resection) (HR =
      0.48; 95%CI: 0.30-0.77, P = 0.003) were independent favorable prognostic factors.
      Among the 96 patients, 20 patients survived for 5 years or more, and 76 patients
      died within 5 years after operation. Comparison of the 20 5-year survivors with
      the 76 non-survivors showed that lower concentrations of DUPAN-2 (79.5 vs 312.5
      U/mL, P = 0.032), tumor size <= 20 mm (35% vs 8%, P = 0.008), R0 resection (95%
      vs 61%, P = 0.004), and absence of lymph node metastases (60% vs 18%, P = 0.036)
      were significantly associated with the 5-year survival. CONCLUSION: Negative
      surgical margins and a tumor size <= 20 mm were independent favorable prognostic
      factors. Histologically curative resection and early tumor detection are
      important factors in achieving long-term survival.

PMID- 25574101
TI  - Clinical outcomes of small cell neuroendocrine carcinoma and adenocarcinoma of
      the gallbladder.
AB  - AIM: To compare the demographics and survival rates between gallbladder
      adenocarcinoma (GB-adenocarcinoma) and small cell neuroendocrine carcinoma of the
      gallbladder (GB-NEC-SCC). METHODS: From March 2007 to September 2012, patients
      who underwent resection of tumor stage T2/T3 GB cancer were enrolled for this
      study. Forty-two patients were included in this study, including 38 diagnosed
      with GB-adenocarcinoma and four diagnosed with GB-NEC-SCC. In the GB
      adenocarcinoma group, a radical operation was performed in 28 patients, and ten
      patients underwent simple cholecystectomy. In the GB-NEC-SCC group, a radical
      operation was performed in three patients, and one patient underwent simple
      cholecystectomy. Comparative analysis of the two groups was performed, including
      clinicopathologic features and survival rates. RESULTS: The median age of the
      patients was 68 y (range: 35-83 years) and females comprised 26/42 of the
      patients. GB-adenocarcinoma patients were significantly older than GB-NEC-SCC
      patients (67.89 +/- 11.15 vs 55.75 +/- 10.31 years; P = 0.029). The median tumor
      size in GB-adenocarcinoma patients was 2.56 +/- 1.75 cm and 3.98 +/- 3.74 cm in
      GB-NEC-SCC patients; however, there was no significant difference between the two
      groups. For tumors > 2 cm, T stage (T2 vs T3), lymphovascular invasion,
      perineural invasion, lymph node metastasis and lymph node ratio showed no
      significant differences between the two groups. The overall survival rate of the
      42 patients at five years was 77.0%. In the GB-adenocarcinoma group, the overall
      five-year survival rate was 74.8%, and survival in the GB-NEC-SCC group was 100%,
      which was not significantly different between the two groups. CONCLUSION: The
      strategy for treating patients with GB-NEC-SCC should be similar to that used for
      treating GB-adenocarcinoma, including radical cholecystectomy and liver
      resection.

PMID- 25574102
TI  - Morphologic factors of biliary trees are associated with gallstone-related
      biliary events.
AB  - AIM: To determine the risk factors for gallstone-related biliary events. METHODS:
      This retrospective cohort study evaluated magnetic resonance
      cholangiopancreatography images from 141 symptomatic and 39 asymptomatic
      gallstone patients who presented at a single tertiary hospital between January
      2005 and December 2012. RESULTS: Logistic regression analysis showed significant
      differences between symptomatic and asymptomatic patients with gallstones in
      relation to the number of gallstones, the angle between the long axis of the
      gallbladder and the cystic duct, and the cystic duct diameter. Multivariate
      analysis showed that the number of gallstones (OR = 1.27, 95%CI: 1.03-1.57; P =
      0.026), the angle between the long axis of the gallbladder and the cystic duct
      (OR = 1.02, 95%CI: 1.00-1.03; P = 0.015), and the diameter of the cystic duct (OR
      = 0.819, 95%CI: 0.69-0.97; P = 0.018) were significantly associated with biliary
      events. The incidence of biliary events was significantly elevated in patients
      who had the presence of more than two gallstones, an angle of > 92 degrees 
      between the gallbladder and the cystic duct, and a cystic duct diameter < 6 mm.
      CONCLUSION: These findings will help guide the treatment of patients with
      asymptomatic gallstones. Clinicians should closely monitor patients with
      asymptomatic gallstones who exhibit these characteristics.

PMID- 25574104
TI  - Latent structure of irritable bowel syndrome symptom severity.
AB  - AIM: To investigate the latent structure of an irritable bowel syndrome (IBS)
      symptom severity scale in a population of healthy adults. METHODS: The Birmingham
      IBS symptom questionnaire which consists of three symptom specific scales
      (diarrhea, constipation, pain) was evaluated by means of structural equation
      modeling. We compared the original 3-factor solution to a general factor model
      and a bifactor solution in a large internet sample of college students (n = 875).
      Statistical comparisons of competing models were conducted by means of chi (2)
      difference tests. Regarding the evaluation of model fit, we examined the
      comparative fit index (CFI) and the Root Mean Square Error of Approximation
      (RMSEA). RESULTS: Results clearly favored a bifactor model of IBS symptom
      severity (CFI = 0.99, RMSEA = 0.05) which consisted of a strong general IBS
      somatization factor and three symptom specific factors (diarrhea, constipation,
      pain) based on the subscales of the Birmingham IBS symptom questionnaire. The fit
      indices of the competing one factor model (CFI = 0.85, RMSEA = 0.17) and three
      factor model (CFI = 0.97, RMSEA = 0.08) were clearly inferior. chi (2) difference
      tests showed that the differences between the models were indeed significant in
      favor of the bifactor model (P < 0.001). Correlations of the four latent factors
      with measures of pain sensitivity, somatoform dissociation, fatigue severity, and
      demographic variables support the validity of our bifactor model of IBS specific
      symptom severity. CONCLUSION: The findings suggest that IBS symptom severity
      might best be understood as a continuous and multidimensional construct which can
      be reliably and validly assessed with the B-IBS.

PMID- 25574103
TI  - Autoantibodies in Chinese patients with chronic hepatitis B: prevalence and
      clinical associations.
AB  - AIM: To investigate the prevalence of autoantibodies and their associations with
      clinical features in Chinese patients with chronic hepatitis B (CHB). METHODS: A
      total of 325 Chinese patients with CHB were enrolled in this retrospective,
      hospital-based study. Patients with chronic hepatitis C (CHC), autoimmune
      hepatitis (AIH), or primary biliary cirrhosis (PBC) were included, with healthy
      donors acting as controls. A panel of autoantibodies that serologically define
      AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay.
      The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies
      (ANA-H), smooth-muscle antibodies, anti-liver kidney microsome type 1, anti-liver
      cytosolic antigen type 1, and anti-soluble liver antigen/liver pancreas; the PBC
      related antibodies were characterized by ANA-nuclear dots/membranous rim-like,
      anti-mitochondrial antibodies-M2 (AMA-M2), anti-BPO (recombinant antigen targeted
      by AMA-M2), anti-Sp100, anti-promyelocytic leukemia protein (anti-PML), and anti
      gp210. The dichotomization of clustering was used to unequivocally designate the
      AIH or PBC profiles for each case. Anti-Ro52 antibodies were also tested.
      RESULTS: The prevalence of any autoantibody in CHB amounted to 58.2%, which was
      similar to the 66.2% prevalence in CHC, significantly higher than the 6.7% in the
      healthy controls (P < 0.001), and lower than the 100% found in AIH and PBC (P =
      0.004 and P < 0.001, respectively). There were more anti-PML and anti-gp210
      antibodies among the CHB patients than the CHC patients (11.1% vs 0%, P = 0.003;
      12.6% vs 0%, P < 0.001, respectively). The prevalence and titer of AMA, anti-BPO,
      anti-PML, and anti-gp210 were higher in PBC than in those with CHB. Among the CHB
      patients, the prevalence of ANA, especially ANA-H, was significantly lower in
      patients with compensated and decompensated cirrhosis compared with patients
      without cirrhosis. Thirty-eight cases of hepatocellular carcinoma (HCC) in CHB
      showed a significant difference compared with non-HCC patients in the prevalence
      of anti-PML (0% vs 12.5%, P = 0.013). Dichotomization of the autoantibodies
      revealed that the PBC profile was more prevalent in patients with CHB than in
      those with CHC, and that it was strongly correlated with both compensated and
      decompensated cirrhosis. In contrast, the prevalence of the AIH profile was
      significantly higher in non-cirrhosis patients with CHB than in those with
      compensated cirrhosis (18.5% vs 8.2%, P = 0.039). Moreover, the AIH profile was
      also closely associated with hepatitis B e-antigen positivity. CONCLUSION: ANA-H
      could be an indicator of early-stage CHB. Dichotomizing the autoantibody profiles
      revealed that the PBC profile is strongly associated with cirrhosis in CHB.

PMID- 25574105
TI  - Fatty acid changes help to better understand regression of nonalcoholic fatty
      liver disease.
AB  - AIM: To investigate whether liver steatosis reduction due to a six-month dietary
      intervention results in significant changes in the concentrations of fatty acids.
      METHODS: A group of 35 Caucasian individuals diagnosed with different levels of
      steatosis were prospectively enrolled in the present study. Analysis of the fatty
      acid profiles was performed according to changes in liver steatosis (liver
      steatosis reduction by one or two degrees) after a six-month dietary
      intervention. The diet helped reduce body mass in obese and overweight patients,
      and stabilize both glycemia and dyslipidemia. Fatty acids were extracted
      according to the Folch method and analyzed by gas chromatography. RESULTS: This
      study showed significant changes in fatty acid profiles in patients who had
      reduced liver steatosis by one as well as two degrees. A reduction in liver
      steatosis by one degree caused a significant increase in the level of the n-3
      family: eicosapentaenoic acid (P < 0.055), docosapentaenoic acid-C 22:5 (P <
      0.05) and docosahexaenoic acid (P < 0.05). A reduction in liver steatosis by two
      degrees caused a significant decrease in serum palmitoleic acid-C 16:1 (P <
      0.05). CONCLUSION: Liver steatosis reduction is associated with changes in fatty
      acid profiles, and these changes may reflect an alteration in fatty acid
      synthesis and metabolism. These findings may help better understand regression of
      nonalcoholic fatty liver disease.

PMID- 25574106
TI  - Common telomerase reverse transcriptase promoter mutations in hepatocellular
      carcinomas from different geographical locations.
AB  - AIM: To determine the mutation status of human telomerase reverse transcriptase
      gene (TERT) promoter region in hepatocellular carcinoma (HCC) from different
      geographical regions. METHODS: We analyzed the genomic DNA sequences of 59 HCC
      samples comprising 15 cell lines and 44 primary tumors, collected from patients
      living in Asia, Europe and Africa. We amplified a 474 bp DNA fragment of the
      promoter region of TERT gene including the 1295228 and 1295250 sequence of
      chromosome 5 by using PCR. Amplicons were then sequenced by Sanger technique and
      the sequence data were analyzed with by using DNADynamo software in comparison
      with wild type TERT gene sequence as a reference. RESULTS: The TERT mutations
      were found highly frequent in HCC. Eight of the fifteen tested cell lines
      displayed C228T mutation, and one had C250T mutation with a mutation frequency up
      to 60%. All of the mutations were heterozygous and mutually exclusive. Ten out of
      forty-four tumors displayed C228T mutation, and additional five tumors had C250T
      mutation providing evidence for mutation frequency of 34% in primary tumors.
      Considering the geographic origins of HCC tumors tested, TERT promoter mutation
      frequencies were higher in African (53%), when compared to non-African (24%)
      tumors (P = 0.056). There was also a weak inverse correlation between TERT
      promoter mutations and murine double minute 2 single nucleotide polymorphism 309
      TG polymorphism (P = 0.058). Mutation frequency was nearly two times higher in
      established HCC cell lines (60%) compared to the primary tumors (34%).
      CONCLUSION: TERT promoter is one of most frequent mutational targets in liver
      cancer, and hepatocellular carcinogenesis is highly associated with the loss of
      telomere-dependent cellular senescence control.

PMID- 25574107
TI  - Long-term follow-up of distal intestinal obstruction syndrome in cystic fibrosis.
AB  - AIM: To investigate the long-term follow-up of distal intestinal obstruction
      syndrome (DIOS) in Israeli cystic fibrosis (CF) patients. METHODS: This is a
      multi-center, comparative, retrospective study in which we reviewed the medical
      records of all CF patients from three major CF centers in Israel who were treated
      in the period from 1980 to 2012. Patients diagnosed with DIOS were defined as the
      study group. The patients were diagnosed with DIOS based on their clinical
      presentation and typical findings on either abdominal X-ray or computerized
      tomography scan. For the control group, CF patients with no DIOS were matched to
      the patients in the study group for age, sex, and cystic fibrosis transmembrane
      conductance regulator (CFTR) mutations. For both groups, the collected data
      included age, sex, CFTR genotype, weight, height, and body mass index. Clinical
      data included respiratory function tests in the last five years prior to the
      study, respiratory function test immediately before and after the DIOS event,
      number of hospitalizations, sputum culture results, and CF-related conditions
      diagnosed according to the CF clinical practice guidelines. In the study group,
      data on the DIOS treatment and tendency for DIOS recurrence were also analyzed.
      RESULTS: The medical charts for a total of 350 CF patients were reviewed. Of the
      350 CF patients, 26 (7.4%) were diagnosed with DIOS. The control group included
      31 CF patients with no DIOS diagnosis. The mean follow-up period was 21.6 +/- 8.2
      years. The total of DIOS episodes in the follow-up period was 60. The
      distribution of DIOS episodes was as follows: 6/26 (23.1%) study patients had one
      episode of DIOS in their lifetime, 7/26 (26.9%) had two episodes, 7/26 (26.9%)
      had three episodes, and 6/26 (23.1%) had four or more episodes. Compared to the
      control group, DIOS patients had a significantly higher incidence of meconium
      ileus in the past (65.4% vs 0%, respectively, P < 0.02), more Aspergillus spp.
      colonization (34.6% vs 3.2%, respectively, P < 0.02), and a higher number of
      hospitalizations due to respiratory exacerbations (8.6 vs 6.2 mean total
      hospitalizations per follow-up period, respectively, P < 0.02). No other
      significant differences were found between the control and study groups. The
      conservative treatment of DIOS, which mainly includes hydration and stool
      softeners, was successful in 82% of the episodes. The survival rate was similar
      for both groups. CONCLUSION: CF patients with DIOS suffer from recurrent
      hospitalizations and airway pathogen acquisition. Although recurrence of DIOS is
      common, conservative treatment is successful in most patients.

PMID- 25574108
TI  - Impact of fecal occult blood on obscure gastrointestinal bleeding: observational
      study.
AB  - AIM: To elucidate the association between small bowel diseases (SBDs) and
      positive fecal occult blood test (FOBT) in patients with obscure gastrointestinal
      bleeding (OGIB). METHODS: Between February 2008 and August 2013, 202 patients
      with OGIB who performed both capsule endoscopy (CE) and FOBT were enrolled (mean
      age; 63.6 +/- 14.0 years, 118 males, 96 previous overt bleeding, 106 with occult
      bleeding). All patients underwent immunochemical FOBTs twice prior to CE. Three
      experienced endoscopists independently reviewed CE videos. All reviews and
      consensus meeting were conducted without any information on FOBT results. The
      prevalence of SBDs was compared between patients with positive and negative FOBT.
      RESULTS: CE revealed SBDs in 72 patients (36%). FOBT was positive in 100 patients
      (50%) and negative in 102 (50%). The prevalence of SBDs was significantly higher
      in patients with positive FOBT than those with negative FOBT (46% vs 25%, P =
      0.002). In particular, among patients with occult OGIB, the prevalence of SBDs
      was higher in positive FOBT group than negative FOBT group (45% vs 18%, P =
      0.002). On the other hand, among patients with previous overt OGIB, there was no
      significant difference in the prevalence of SBDs between positive and negative
      FOBT group (47% vs 33%, P = 0.18). In disease specific analysis among patients
      with occult OGIB, the prevalence of ulcer and tumor were higher in positive FOBT
      group than negative FOBT group. In multivariate analysis, only positive FOBT was
      a predictive factors of SBDs in patients with OGIB (OR = 2.5, 95%CI: 1.4-4.6, P =
      0.003). Furthermore, the trend was evident among patients with occult OGIB who
      underwent FOBT on the same day or a day before CE. The prevalence of SBDs in
      positive vs negative FOBT group were 54% vs 13% in patients with occult OGIB who
      underwent FOBT on the same day or the day before CE (P = 0.001), while there was
      no significant difference between positive and negative FOBT group in those who
      underwent FOBT two or more days before CE (43% vs 25%, P = 0.20). CONCLUSION: The
      present study suggests that positive FOBT may be useful for predicting SBDs in
      patients with occult OGIB. Positive FOBT indicates higher likelihood of ulcers or
      tumors in patients with occult OGIB. Undergoing CE within a day after FOBT
      achieved a higher diagnostic yield for patients with occult OGIB.

PMID- 25574109
TI  - Circulating Metastasis Associated in Colon Cancer 1 transcripts in gastric cancer
      patient plasma as diagnostic and prognostic biomarker.
AB  - AIM: To evaluate the diagnostic and prognostic value of circulating Metastasis
      Associated in Colon Cancer 1 (MACC1) transcripts in plasma of gastric cancer
      patients. METHODS: We provide for the first time a blood-based assay for
      transcript quantification of the metastasis inducer MACC1 in a prospective study
      of gastric cancer patient plasma. MACC1 is a strong prognostic biomarker for
      tumor progression and metastasis in a variety of solid cancers. We conducted a
      study to define the diagnostic and prognostic power of MACC1 transcripts using 76
      plasma samples from gastric cancer patients, either newly diagnosed with gastric
      cancer, newly diagnosed with metachronous metastasis of gastric cancer, as well
      as follow-up patients. Findings were controlled by using plasma samples from 54
      tumor-free volunteers. Plasma was separated, RNA was isolated, and levels of
      MACC1 as well as S100A4 transcripts were determined by quantitative RT-PCR.
      RESULTS: Based on the levels of circulating MACC1 transcripts in plasma we
      significantly discriminated tumor-free volunteers and gastric cancer patients (P
      < 0.001). Levels of circulating MACC1 transcripts were increased in gastric
      cancer patients of each disease stage, compared to tumor-free volunteers:
      patients with tumors without metastasis (P = 0.005), with synchronous metastasis
      (P = 0.002), with metachronous metastasis (P = 0.005), and patients during follow
      up (P = 0.021). Sensitivity was 0.68 (95%CI: 0.45-0.85) and specificity was 0.89
      (95%CI: 0.77-0.95), respectively. Importantly, gastric cancer patients with high
      circulating MACC1 transcript levels in plasma demonstrated significantly shorter
      survival when compared with patients demonstrating low MACC1 levels (P = 0.0015).
      Furthermore, gastric cancer patients with high circulating transcript levels of
      MACC1 as well as of S100A4 in plasma demonstrated significantly shorter survival
      when compared with patients demonstrating low levels of both biomarkers or with
      only one biomarker elevated (P = 0.001). CONCLUSION: Levels of circulating MACC1
      transcripts in plasma of gastric cancer patients are of diagnostic value and are
      prognostic for patient survival in a prospective study.

PMID- 25574110
TI  - Human papillomavirus does not have a causal role in colorectal carcinogenesis.
AB  - AIM: To investigate the presence of human papillomavirus (HPV) DNA along with the
      integration, the quantification and the expression of the HPV16 in colorectal
      cancers. METHODS: A prospective series of colorectal tumors were genotyped for
      HPV DNA. The clinical and pathological variables of the HPV-positive tumors were
      compared to those of HPV-negative samples. The integration status of HPV16 was
      evaluated by calculating E2/E6 ng ratios. HPV16-positive tumors were also
      evaluated for (1) E2, E4, E5, E6 and E7 viral gene ng quantification; (2)
      relative quantification compared to W12 cells; and (3) viral E2, E4, E5, E6 and
      E7 mRNA transcripts by real-time polymerase chain reaction. RESULTS: HPV
      infection was detected in 16.9% of all tumors examined, and HPV16 was the most
      frequent type detected (63.6% of positive tissues). Notably, the clinical and
      pathological features of HPV-positive colorectal cancers were not significantly
      different than those of HPV-negative cancers (chi (2) and t-test for all clinical
      and pathological features of HPV-positive vs HPV-negative colorectal cancers: p
      ns). HPV16 DNA was present exclusively in episomal form, and the HPV16 E2, E4,
      E5, E6 and E7 genes were detected in trace nanogram quantities. Furthermore, the
      HPV16 genes ranged from 10(-3) to 10(-9) compared to W12 cells at an episomal
      stage. Although the extractions were validated by housekeeping gene expression,
      all the HPV16 positive tissues were transcriptionally inactive for the E2, E4,
      E5, E6 and E7 mRNAs. CONCLUSION: Based on our results, HPV is unlikely involved
      in colorectal carcinogenesis.

PMID- 25574113
TI  - Indocyanine green fluorescence and three-dimensional imaging of right
      gastroepiploic artery in gastric tube cancer.
AB  - A 79-year-old male was admitted to our hospital for the treatment of cancer of
      the gastric tube. Gastrointestinal examination revealed a T1b Union for
      International Cancer Control (UICC) tumor at the pyloric region of the gastric
      tube. Laparotomy did not reveal infiltration into the serosa, peritoneal
      dissemination, regional lymph node swelling, or distant metastasis. We performed
      a distal gastrectomy preserving the right gastroepiploic artery by referencing
      the preoperative three-dimensional computed tomoangiography. We also evaluated
      the blood flow of the right gastroepiploic artery and in the proximal gastric
      tube by using indocyanine green fluorescence imaging intra-operatively and then
      followed with a gastrojejunal anastomosis with Roux-en-Y reconstruction. The
      definitive diagnosis was moderately differentiated adenocarcinoma of the gastric
      tube, pT1bN0M0, pStage IA (UICC). His postoperative course was uneventful. Three
      dimensional computed tomographic imaging is effective for assessing the course of
      blood vessels and the relationship with the surrounding structures.
      Intraoperative evaluation of blood flow of the right gastroepiploic artery and of
      the gastric tube in the anastomotic portion is very valuable information and
      could contribute to a safe gastrointestinal reconstruction.

PMID- 25574114
TI  - Placement of 125I seed strands and stents for a type IV Klatskin tumor.
AB  - Herein, we report a new technique that consists of placing two (125)I seed
      strands and two stents in the right and left intrahepatic bile ducts for the
      treatment of hilar cholangiocarcinoma. A 75-year-old man presented with jaundice
      and was diagnosed with Bismuth type IV Klatskin tumor. Abdominal computed
      tomography (CT) showed intrahepatic and extrahepatic bile duct dilatation and a
      soft tissue mass in the hepatic hilum. Because curative surgical resection was
      not possible, we placed (125)I seed strands and stents in the right and left
      intrahepatic bile ducts. Three months later, abdominal CT showed less
      intrahepatic and extrahepatic bile duct dilatation than before the procedure.
      This technique was feasible and could be considered for the treatment of patients
      with Bismuth type IV tumors. 

PMID- 25574115
TI  - Re: ''laparoscopic vs open approach to resection of hepatocellular carcinoma in
      patients with known cirrhosis: systematic review and meta-analysis''.
AB  - Twaij and colleagues have carried out a meta-analysis of cohort studies to review
      the currently available literature comparing laparoscopic to open resection of
      hepatocellular carcinoma in patients with known liver cirrhosis. We congratulate
      and applaud their important work, but several important issues should be noted.

PMID- 25574111
TI  - Concomitant therapy achieved the best eradication rate for Helicobacter pylori
      among various treatment strategies.
AB  - AIM: To compare the Helicobacter pylori (H. pylori) eradication rate of
      clarithromycin-based triple therapy, metronidazole-based triple therapy,
      sequential therapy and concomitant therapy. METHODS: A total of 680 patients
      infected with H. pylori were divided into 4 groups and each group was treated
      with a different eradication therapy. Clarithromycin-based triple therapy was
      applied to the first group [rabeprazole, amoxicillin and clarithromycin (PAC)
      group: proton pump inhibitor (PPI), amoxicillin, clarithromycin], whereas the
      second group was treated with metronidazole-based triple therapy [rabeprazole,
      amoxicillin and metronidazole (PAM) group: PPI, amoxicillin, metronidazole]. The
      third group was treated with rabeprazole and amoxicillin, followed by
      rabeprazole, clarithromycin and metronidazole (sequential group). The final group
      was simultaneously treated with rabeprazole, amoxicillin clarithromycin and
      metronidazole (concomitant therapy group). In the case of a failure to eradicate
      H. pylori, second-line quadruple and third-line eradication therapies were
      administered. RESULTS: The per protocol (PP) analysis was performed on 143, 139,
      141 and 143 patients in the PAC, PAM, sequential and concomitant groups,
      respectively. We excluded patients who did not receive a C(13)-urea breath test
      (22, 20, 23 and 22 patients, respectively) and patients with less than an 80%
      compliance level (5, 11, 6 and 5 patients, respectively). The eradication rates
      were 76.2% (109/143) in the PAC group, 84.2% (117/139) in the PAM group, 84.4%
      (119/141) in the sequential group and 94.4% (135/143) in the concomitant group (P
      = 0.0002). All 14 patients who failed second-line therapy were treated with third
      line eradication therapy. Among these 14 patients, 6 infections were successfully
      eradicated with the third-line therapy. Both PP and intention-to-treat analysis
      showed an eradication rate of 42.9% (6/14). In the PAC group, 3 of 4 patients
      were successfully cured (3/4, 75%); 2 of 2 patients in the PAM group (2/2, 100%)
      and 1 of 5 patients in the sequential group (1/5, 20%) were also cured. In the
      concomitant group, all 3 patients failed (0/3, 0%). CONCLUSION: The eradication
      rate for the concomitant therapy was much higher than those of the standard
      triple therapy or sequential therapy (ClinicalTrials.gov number NCT01922765).

PMID- 25574112
TI  - Giant colonic diverticulum: clinical presentation, diagnosis and treatment:
      systematic review of 166 cases.
AB  - AIM: To investigate the clinical presentation, diagnosis, and treatment of giant
      colonic diverticulum (GCD, by means of a complete and updated literature review).
      GCD is a rare manifestation of diverticular disease of the colon. Less than 200
      studies on GCD were published in the literature, predominantly case reports or
      small patient series. METHODS: A systematic review of the literature was
      performed using the Embase and PubMed databases to identify all the GCD studies.
      The following MESH search headings were used: "giant colonic diverticulum";
      "giant sigmoid diverticulum". The "related articles" function was used to broaden
      the search, and all of the abstracts, studies, and citations were reviewed by two
      authors. The following outcomes were of interest: the disease and patient
      characteristics, study design, indications for surgery, type of operation, and
      post-operative outcomes. Additionally, a subgroup analysis of cases treated in
      the last 5 years was performed to show the current trends in the treatment of
      GCD. A GCD case in an elderly patient treated in our department by a
      sigmoidectomy with primary anastomosis and a diverting ileostomy is presented as
      a typical example of the disease. RESULTS: In total, 166 GCD cases in 138 studies
      were identified in the literature. The most common clinical presentation was
      abdominal pain, which occurred in 69% of the cases. Among the physical signs, an
      abdominal mass was detected in 48% of the cases, whereas 20% of the patients
      presented with fever and 14% with abdominal tenderness. Diagnosis is based
      predominantly on abdominal computed tomography. The most frequent treatment was
      colic resection with en-bloc resection of the diverticulum, performed in 57.2% of
      cases, whereas Hartmann's procedure was followed in 11.4% of the cases and a
      diverticulectomy in 10.2%. An analysis of sixteen cases reported in the last 5
      years showed that the majority of patients were treated with sigmoidectomy and en
      bloc resection of the diverticulum; the postoperative mortality was null,
      morbidity was very low (1 patient was hospitalized in the intensive care unit for
      postoperative hypotension), and the patients were discharged 4-14 d after
      surgery. CONCLUSION: Giant colonic diverticulum is a rare manifestation of
      diverticular diseases. Surgical treatment, consisting predominantly of colonic
      resection with en bloc resection of the diverticulum, is the preferred option for
      GCD and guarantees excellent results.

PMID- 25574116
TI  - Fidaxomicin Use and Clinical Outcomes for Clostridium difficile-Associated
      Diarrhea.
AB  - BACKGROUND: Fidaxomicin has been scrutinized because of its high acquisition
      cost. Real-world experience is needed to determine whether fidaxomicin has value
      in patients with Clostridium difficile-associated diarrhea (CDAD) and certain
      risk factors. METHODS: In this single-center, retrospective cohort study,
      patients 18 years or older with diarrheal symptoms and positive polymerase chain
      reaction assay for C. difficile toxin B gene or pseudomembranes were administered
      fidaxomicin between August 2011 and March 2013. Clinical success was defined as
      the resolution of signs and symptoms of disease and no further therapy required
      for CDAD as of the second day after cessation of fidaxomicin therapy. The
      recurrence of CDAD was defined by the reappearance of signs and symptoms of
      disease after the cessation of therapy, a new positive C. difficile polymerase
      chain reaction result, and the need for CDAD retreatment. Readmissions were
      tracked for 90 days after hospital discharge. RESULTS: Of the 60 patients who
      received fidaxomicin, 58 (96.7%) achieved clinical success. Twenty-six (43.3%) of
      the 60 patients were being treated for a second or greater episode. Six (10.3%)
      of the 58 patients had recurrence within 90 days after the initial treatment
      course, and 4 (6.9%) were readmitted within 30 days after hospital discharge.
      CONCLUSIONS: In this real-world setting, fidaxomicin resulted in a high rate of
      clinical success, a low rate of recurrence, and a low readmission rate.

PMID- 25574117
TI  - Ceftaroline Fosamil for the Treatment of Staphylococcus aureus Bacteremia
      Secondary to Acute Bacterial Skin and Skin Structure Infections or Community
      Acquired Bacterial Pneumonia.
AB  - BACKGROUND: The Clinical Assessment Program and Teflaro(r) Utilization Registry
      is designed to collect information on the clinical use of ceftaroline fosamil in
      the Unites States. This report presents data on the treatment of patients with
      Staphylococcus aureus bacteremia (SAB) secondary to acute bacterial skin and skin
      structure infections (ABSSSIs) or community-acquired bacterial pneumonia (CABP).
      METHODS: Patients diagnosed with ABSSSI or CABP were identified through
      sequential review of randomly ordered charts generated from pharmacy listings
      from August 2011 to February 2013. Data were collected by chart review 30 days or
      more after completion of ceftaroline fosamil therapy. RESULTS: Secondary SAB was
      reported in a total of 48 of 1428 evaluable patients (27 with ABSSSI, 21 with
      CABP). The mean (SD) patient age was 61 (15) years. At least 1 comorbidity was
      recorded for 74% of patients with ABSSSI and 81% with CABP. Methicillin-resistant
      S. aureus was isolated from 59% of patients with ABSSSI and 76% with CABP. The
      mean (SD) duration of ceftaroline fosamil therapy was 5.8 (4.8) days for ABSSSI
      and 7.0 (3.8) days for CABP. Clinical success among all patients with SAB treated
      with ceftaroline fosamil was 58% (52% for SAB secondary to ABSSSI, 67% for SAB
      secondary to CABP). Clinical success rates of methicillin-resistant S. aureus SAB
      were 50% (8/16) for ABSSSI and 63% (10/16) for CABP. CONCLUSIONS: This study
      supports the use of ceftaroline fosamil as a viable treatment option in
      hospitalized patients with SAB secondary to ABSSSI or CABP. Further studies
      evaluating the use of ceftaroline fosamil for the treatment of SAB are warranted.

PMID- 25574118
TI  - Feedback Support for Training: Accounting for Learner and Task.
AB  - Years of research on feedback has not produced universal prescriptions for
      feedback during training. Results are split in two directions; those recommending
      more feedback during training and those recommending less. This has resulted in
      no unified theory and little understanding of other factors that might affect
      feedback mechanisms. The current experiment manipulated the cognitive load of the
      task and measured the working memory capacities of the learners to see whether
      forcing the learner to self-evaluate affects learning of a cognitive task and how
      this might be moderated by learner ability and task load. Results generally
      showed that reducing task load through supportive feedback resulted in more
      learning.

PMID- 25574119
TI  - Watching Their Steps: Integrating Vision Intervention Into Daily Practice to
      Limit Fall Risk at Skilled Nursing Facilities.
AB  - Strategies that address decreased vision are an important part of multifactorial
      interventions to prevent falls and facilitate safe participation in valued
      occupations.

PMID- 25574120
TI  - Evaluating the accuracy and efficiency of multiple sequence alignment methods.
AB  - A comparison of 10 most popular Multiple Sequence Alignment (MSA) tools, namely,
      MUSCLE, MAFFT(L-INS-i), MAFFT (FFT-NS-2), T-Coffee, ProbCons, SATe, Clustal
      Omega, Kalign, Multalin, and Dialign-TX is presented. We also focused on the
      significance of some implementations embedded in algorithm of each tool. Based on
      10 simulated trees of different number of taxa generated by R, 400 known
      alignments and sequence files were constructed using indel-Seq-Gen. A total of
      4000 test alignments were generated to study the effect of sequence length, indel
      size, deletion rate, and insertion rate. Results showed that alignment quality
      was highly dependent on the number of deletions and insertions in the sequences
      and that the sequence length and indel size had a weaker effect. Overall,
      ProbCons was consistently on the top of list of the evaluated MSA tools. SATe,
      being little less accurate, was 529.10% faster than ProbCons and 236.72% faster
      than MAFFT(L-INS-i). Among other tools, Kalign and MUSCLE achieved the highest
      sum of pairs. We also considered BALiBASE benchmark datasets and the results
      relative to BAliBASE- and indel-Seq-Gen-generated alignments were consistent in
      the most cases. 

PMID- 25574121
TI  - Functional Implications of RNA Splicing for Human Long Intergenic Noncoding RNAs.
AB  - Long intergenic noncoding RNAs (lincRNAs) have been suggested as playing
      important roles in human gene regulation. The majority of annotated human
      lincRNAs include multiple exons and are alternatively spliced. However, the
      connections between alternative RNA splicing (AS) and the functions/regulations
      of lincRNAs have remained elusive. In this study, we compared the sequence
      evolution and biological features between single-exonic lincRNAs and multi-exonic
      lincRNAs (SELs and MELs, respectively) that were present only in the hominoids
      (hominoid-specific) or conserved in primates (primate-conserved). The MEL exons
      were further classified into alternatively spliced exons (ASEs) and
      constitutively spliced exons (CSEs) for evolutionary analyses. Our results
      indicate that SELs and MELs differed significantly from each other. Firstly, in
      hominoid-specific lincRNAs, MELs (both CSEs and ASEs) evolved slightly more
      rapidly than SELs, which evolved approximately at the neutral rate. In primate
      conserved lincRNAs, SELs and ASEs evolved slightly more slowly than CSEs and
      neutral sequences. The evolutionary path of hominid-specific lincRNAs thus seemed
      to have diverged from that of their more ancestral counterparts. Secondly, both
      of the exons and transcripts of SELs were significantly longer than those of
      MELs, and this was probably because SEL transcripts were more resistant to RNA
      splicing than MELs. Thirdly, SELs were physically closer to coding genes than
      MELs. Fourthly, SELs were more widely expressed in human tissues than MELs. These
      results suggested that SELs and MELs represented two biologically distinct groups
      of genes. In addition, the SEL-MEL and ASE-CSE differences implied that splicing
      might be important for the functionality or regulations of lincRNAs in primates. 

PMID- 25574122
TI  - In silico detection of virulence gene homologues in the human pathogen
      sphingomonas spp.
AB  - There is an ongoing debate about the clinical significance of Sphingomonas
      paucimobilis as a virulent bacterial pathogen. In the present study, we
      investigated the presence of different virulence factors and genes in
      Sphingomonas bacteria. We utilized phylogenetic, comparative genomics and
      bioinformatics analysis to investigate the potentiality of Sphingomonas bacteria
      as virulent pathogenic bacteria. The 16S ribosomal RNA gene (16S rDNA)
      phylogenetic tree showed that the closest bacterial taxon to Sphingomonas is
      Brucella with a bootstrap value of 87 followed by Helicobacter, Campylobacter,
      Pseudomonas, and then Legionella. Sphingomonas shared no virulence factors with
      Helicobacter or Campylobacter, despite their close phylogenic relationship. In
      spite of the phylogenetic divergence between Sphingomonas and Pseudomonas, they
      shared many major virulence factors, such as adherence, antiphagocytosis, iron
      uptake, proteases, and quorum sensing. In conclusion, Sphingomonas spp. contains
      several major virulence factors resembling Pseudomonas sp., Legionella sp.,
      Brucella sp., and Bordetella sp. virulence factors. Similarity of virulence
      factors did not match phylogenetic relationships. These findings suggest
      horizontal gene transfer of virulence factors rather than sharing a common
      pathogenic ancestor. Sphingomonas spp. is potential virulent bacterial pathogen. 

PMID- 25574123
TI  - Computational analysis reveals a successive adaptation of multiple inositol
      polyphosphate phosphatase 1 in higher organisms through evolution.
AB  - Multiple inositol polyphosphate phosphatase 1 (Minpp1) in higher organisms
      dephosphorylates InsP6, the most abundant inositol phosphate. It also
      dephosphorylates less phosphorylated InsP5 and InsP4 and more phosphorylated
      InsP7 or InsP8. Minpp1 is classified as a member of the histidine acid
      phosphatase super family of proteins with functional resemblance to phytases
      found in lower organisms. This study took a bioinformatics approach to explore
      the extent of evolutionary diversification in Minpp1 structure and function in
      order to understand its physiological relevance in higher organisms. The human
      Minpp1 amino acid (AA) sequence was BLAST searched against available national
      protein databases. Phylogenetic analysis revealed that Minpp1 was widely
      distributed from lower to higher organisms. Further, we have identified that
      there exist four isoforms of Minpp1. Multiple computational tools were used to
      identify key functional motifs and their conservation among various species.
      Analyses showed that certain motifs predominant in higher organisms were absent
      in lower organisms. Variation in AA sequences within motifs was also analyzed. We
      found that there is diversification of key motifs and thus their functions
      present in Minpp1 from lower organisms to higher organisms. Another interesting
      result of this analysis was the presence of a glucose-1-phosphate interaction
      site in Minpp1; the functional significance of which has yet to be determined
      experimentally. The overall findings of our study point to an evolutionary
      adaptability of Minpp1 functions from lower to higher life forms. 

PMID- 25574124
TI  - ordinalgmifs: An R Package for Ordinal Regression in High-dimensional Data
      Settings.
AB  - High-throughput genomic assays are performed using tissue samples with the goal
      of classifying the samples as normal < pre-malignant < malignant or by stage of
      cancer using a small set of molecular features. In such cases, molecular features
      monotonically associated with the ordinal response may be important to disease
      development; that is, an increase in the phenotypic level (stage of cancer) may
      be mechanistically linked through a monotonic association with gene expression or
      methylation levels. Though traditional ordinal response modeling methods exist,
      they assume independence among the predictor variables and require the number of
      samples (n) to exceed the number of covariates (P) included in the model. In this
      paper, we describe our ordinalgmifs R package, available from the Comprehensive R
      Archive Network, which can fit a variety of ordinal response models when the
      number of predictors (P) exceeds the sample size (n). R code illustrating usage
      is also provided. 

PMID- 25574125
TI  - Overcome support vector machine diagnosis overfitting.
AB  - Support vector machines (SVMs) are widely employed in molecular diagnosis of
      disease for their efficiency and robustness. However, there is no previous
      research to analyze their overfitting in high-dimensional omics data based
      disease diagnosis, which is essential to avoid deceptive diagnostic results and
      enhance clinical decision making. In this work, we comprehensively investigate
      this problem from both theoretical and practical standpoints to unveil the
      special characteristics of SVM overfitting. We found that disease diagnosis under
      an SVM classifier would inevitably encounter overfitting under a Gaussian kernel
      because of the large data variations generated from high-throughput profiling
      technologies. Furthermore, we propose a novel sparse-coding kernel approach to
      overcome SVM overfitting in disease diagnosis. Unlike traditional ad-hoc
      parametric tuning approaches, it not only robustly conquers the overfitting
      problem, but also achieves good diagnostic accuracy. To our knowledge, it is the
      first rigorous method proposed to overcome SVM overfitting. Finally, we propose a
      novel biomarker discovery algorithm: Gene-Switch-Marker (GSM) to capture
      meaningful biomarkers by taking advantage of SVM overfitting on single genes. 

PMID- 25574126
TI  - Normal cell-type epigenetics and breast cancer classification: a case study of
      cell mixture-adjusted analysis of DNA methylation data from tumors.
AB  - Historically, breast cancer classification has relied on prognostic subtypes.
      Thus, unlike hematopoietic cancers, breast tumor classification lacks
      phylogenetic rationale. The feasibility of phylogenetic classification of breast
      tumors has recently been demonstrated based on estrogen receptor (ER), androgen
      receptor (AR), vitamin D receptor (VDR) and Keratin 5 expression. Four hormonal
      states (HR0-3) comprising 11 cellular subtypes of breast cells have been
      proposed. This classification scheme has been shown to have relevance to clinical
      prognosis. We examine the implications of such phylogenetic classification on DNA
      methylation of both breast tumors and normal breast tissues by applying recently
      developed deconvolution algorithms to three DNA methylation data sets archived on
      Gene Expression Omnibus. We propose that breast tumors arising from a particular
      cell-of-origin essentially magnify the epigenetic state of their original cell
      type. We demonstrate that DNA methylation of tumors manifests patterns consistent
      with cell-specific epigenetic states, that these states correspond roughly to
      previously posited normal breast cell types, and that estimates of proportions of
      the underlying cell types are predictive of tumor phenotypes. Taken together,
      these findings suggest that the epigenetics of breast tumors is ultimately based
      on the underlying phylogeny of normal breast tissue. 

PMID- 25574127
TI  - Growth rate analysis and efficient experimental design for tumor xenograft
      studies.
AB  - Human tumor xenograft studies are the primary means to evaluate the biological
      activity of anticancer agents in late-stage preclinical drug discovery. The
      variability in the growth rate of human tumors established in mice and the small
      sample sizes make rigorous statistical analysis critical. The most commonly used
      summary of antitumor activity for these studies is the T/C ratio. However,
      alternative methods based on growth rate modeling can be used. Here, we describe
      a summary metric called the rate-based T/C, derived by fitting each animal's
      tumor growth to a simple exponential model. The rate-based T/C uses all of the
      data, in contrast with the traditional T/C, which only uses a single measurement.
      We compare the rate-based T/C with the traditional T/C and assess their
      performance through a bootstrap analysis of 219 tumor xenograft studies. We find
      that the rate-based T/C requires fewer animals to achieve the same power as the
      traditional T/C. We also compare 14-day studies with 21-day studies and find that
      14-day studies are more cost efficient. Finally, we perform a power analysis to
      determine an appropriate sample size. 

PMID- 25574128
TI  - Stratified pathway analysis to identify gene sets associated with oral
      contraceptive use and breast cancer.
AB  - Cancer biomarker discovery can facilitate drug development, improve staging of
      patients, and predict patient prognosis. Because cancer is the result of many
      interacting genes, analysis based on a set of genes with related biological
      functions or pathways may be more informative than single gene-based analysis for
      cancer biomarker discovery. The relevant pathways thus identified may help
      characterize different aspects of molecular phenotypes related to the tumor.
      Although it is well known that cancer patients may respond to the same treatment
      differently because of clinical variables and variation of molecular phenotypes,
      this patient heterogeneity has not been explicitly considered in pathway analysis
      in the literature. We hypothesize that combining pathway and patient clinical
      information can more effectively identify relevant pathways pertinent to specific
      patient subgroups, leading to better diagnosis and treatment. In this article, we
      propose to perform stratified pathway analysis based on clinical information from
      patients. In contrast to analysis using all the patients, this more focused
      analysis has the potential to reveal subgroup-specific pathways that may lead to
      more biological insights into disease etiology and treatment response. As an
      illustration, the power of our approach is demonstrated through its application
      to a breast cancer dataset in which the patients are stratified according to
      their oral contraceptive use. 

PMID- 25574129
TI  - Bayesian hierarchical models for protein networks in single-cell mass cytometry.
AB  - We propose a class of hierarchical models to investigate the protein functional
      network of cellular markers. We consider a novel data set from single-cell
      proteomics. The data are generated from single-cell mass cytometry experiments,
      in which protein expression is measured within an individual cell for multiple
      markers. Tens of thousands of cells are measured serving as biological
      replicates. Applying the Bayesian models, we report protein functional networks
      under different experimental conditions and the differences between the networks,
      ie, differential networks. We also present the differential network in a novel
      fashion that allows direct observation of the links between the experimental
      agent and its putative targeted proteins based on posterior inference. Our method
      serves as a powerful tool for studying molecular interactions at cellular level. 

PMID- 25574130
TI  - CARAT-GxG: CUDA-Accelerated Regression Analysis Toolkit for Large-Scale Gene-Gene
      Interaction with GPU Computing System.
AB  - In genome-wide association studies (GWAS), regression analysis has been most
      commonly used to establish an association between a phenotype and genetic
      variants, such as single nucleotide polymorphism (SNP). However, most
      applications of regression analysis have been restricted to the investigation of
      single marker because of the large computational burden. Thus, there have been
      limited applications of regression analysis to multiple SNPs, including gene-gene
      interaction (GGI) in large-scale GWAS data. In order to overcome this limitation,
      we propose CARAT-GxG, a GPU computing system-oriented toolkit, for performing
      regression analysis with GGI using CUDA (compute unified device architecture).
      Compared to other methods, CARAT-GxG achieved almost 700-fold execution speed and
      delivered highly reliable results through our GPU-specific optimization
      techniques. In addition, it was possible to achieve almost-linear speed
      acceleration with the application of a GPU computing system, which is implemented
      by the TORQUE Resource Manager. We expect that CARAT-GxG will enable large-scale
      regression analysis with GGI for GWAS data. 

PMID- 25574131
TI  - Statistical Issues in the Design and Analysis of nCounter Projects.
AB  - Numerous statistical methods have been published for designing and analyzing
      microarray projects. Traditional genome-wide microarray platforms (such as
      Affymetrix, Illumina, and DASL) measure the expression level of tens of thousands
      genes. Since the sets of genes included in these array chips are selected by the
      manufacturers, the number of genes associated with a specific disease outcome is
      limited and a large portion of the genes are not associated. nCounter is a new
      technology by NanoString to measure the expression of a selected number (up to
      800) of genes. The list of genes for nCounter chips can be selected by customers.
      Due to the limited number of genes and the price increase in the number of
      selected genes, the genes for nCounter chips are carefully selected among those
      discovered from previous studies, usually using traditional high-throughput
      platforms, and only a small number of definitely unassociated genes, called
      control genes, are included to standardize the overall expression level across
      different chips. Furthermore, nCounter chips measure the expression level of each
      gene using a counting observation while the traditional high-throughput platforms
      produce continuous observations. Due to these differences, some statistical
      methods developed for the design and analysis of high-throughput projects may
      need modification or may be inappropriate for nCounter projects. In this paper,
      we discuss statistical methods that can be used for designing and analyzing
      nCounter projects. 

PMID- 25574132
TI  - Risk factors associated with serum levels of the inflammatory biomarker soluble
      urokinase plasminogen activator receptor in a general population.
AB  - The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of
      mortality risk in various patient populations. However, little is known about the
      implications of lifestyle for suPAR levels in the general population. Lifestyle,
      demographic, and cardiovascular disease (CVD) risk factor data were collected
      from 5,538 participants in the Danish population-based Inter99 study. Their suPAR
      levels were measured using a sandwich enzyme-linked immunosorbent assay. In the
      final adjusted model, smoking and morbid obesity were strongly associated with
      higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men
      were also associated with higher suPAR levels. Physical activity in leisure time
      had a modest impact on suPAR levels in univariate analysis, but not in the final
      adjusted model. In conclusion, smoking and morbid obesity were strongly
      associated with higher serum suPAR levels in this general population. Diet and
      alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are
      likely to affect suPAR since ex-smokers had suPAR levels comparable to those of
      never-smokers. 

PMID- 25574133
TI  - Genome-wide Analysis of Mycoplasma hominis for the Identification of Putative
      Therapeutic Targets.
AB  - Ever increasing propensity of antibiotic resistance among pathogenic bacteria
      raises the demand for the development of novel therapeutic agents to control this
      grave problem. Advances in the field of bioinformatics, genomics, and proteomics
      have greatly facilitated the discovery of alternative drugs by swift
      identification of new drug targets. In the present study, we employed comparative
      genomics and metabolic pathway analysis with an aim of identifying therapeutic
      targets in Mycoplasma hominis. Our study has revealed 40 annotated metabolic
      pathways, including five unique pathways of M. hominis. Our study also identified
      179 essential proteins, including 59 proteins having no similarity with human
      proteins. Further filtering by molecular weight, subcellular localization,
      functional analysis, and protein network interaction, we identified 57 putative
      candidates for which new drugs can be developed. Druggability analysis for each
      of the identified targets has prioritized 16 proteins as suitable for potential
      drug development. 

PMID- 25574135
TI  - A Hypothetical Protein of Alteromonas macleodii AltDE1 (amad1_06475) Predicted to
      be a Cold-Shock Protein with RNA Chaperone Activity.
AB  - Alteromonas macleodii AltDE1 is a deep sea protobacteria that is distinct from
      the surface isolates of the same species. This study was designed to elucidate
      the biological function of amad1_06475, a hypothetical protein of A. macleodii
      AltDE1. The 70 residues protein sequence showed considerable homology with cold
      shock proteins (CSPs) and RNA chaperones from different organisms. Multiple
      sequence alignment further supported the presence of conserved csp domain on the
      protein sequence. The three-dimensional structure of the protein was also
      determined, and verified by PROCHECK, Verify3D, and QMEAN programs. The predicted
      structure contained five anti-parallel beta-strands and RNA-binding motifs, which
      are characteristic features of prokaryotic CSPs. Finally, the binding of a
      thymidine-rich oligonucleotide and a single uracil molecule in the active site of
      the protein further strengthens our prediction about the function of amad1_06475
      as a CSP and thereby acting as a RNA chaperone. The binding was performed by
      molecular docking tools and was compared with similar binding of 3PF5 (PDB) and
      2HAX (PDB), major CSPs of Bacillus subtilis and Bacillus caldolyticus,
      respectively. 

PMID- 25574134
TI  - A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia.
AB  - Microglia are resident mononuclear phagocytes that play a principal role in the
      maintenance of normal tissue homeostasis in the central nervous system (CNS).
      Microglia, rapidly activated in response to proinflammatory stimuli, are
      accumulated in brain lesions of neurodegenerative diseases, such as Alzheimer's
      disease and Parkinson's disease. The E26 transformation-specific (ETS) family
      transcription factor PU.1/Spi1 acts as a master regulator of myeloid and lymphoid
      development. PU.1-deficient mice show a complete loss of microglia, indicating
      that PU.1 plays a pivotal role in microgliogenesis. However, the comprehensive
      profile of PU.1/Spi1 target genes in microglia remains unknown. By analyzing a
      chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) dataset
      numbered SRP036026 with the Strand NGS program, we identified 5,264 Spi1 target
      protein-coding genes in BV2 mouse microglial cells. They included Spi1, Irf8,
      Runx1, Csf1r, Csf1, Il34, Aif1 (Iba1), Cx3cr1, Trem2, and Tyrobp. By motif
      analysis, we found that the PU-box consensus sequences were accumulated in the
      genomic regions surrounding ChIP-Seq peaks. By using pathway analysis tools of
      bioinformatics, we found that ChIP-Seq-based Spi1 target genes show a significant
      relationship with diverse pathways essential for normal function of
      monocytes/macrophages, such as endocytosis, Fc receptor-mediated phagocytosis,
      and lysosomal degradation. These results suggest that PU.1/Spi1 plays a crucial
      role in regulation of the genes relevant to specialized functions of microglia.
      Therefore, aberrant regulation of PU.1 target genes might contribute to the
      development of neurodegenerative diseases with accumulation of activated
      microglia. 

PMID- 25574136
TI  - POEAS: Automated Plant Phenomic Analysis Using Plant Ontology.
AB  - Biological enrichment analysis using gene ontology (GO) provides a global
      overview of the functional role of genes or proteins identified from large-scale
      genomic or proteomic experiments. Phenomic enrichment analysis of gene lists can
      provide an important layer of information as well as cellular components,
      molecular functions, and biological processes associated with gene lists. Plant
      phenomic enrichment analysis will be useful for performing new experiments to
      better understand plant systems and for the interpretation of gene or proteins
      identified from high-throughput experiments. Plant ontology (PO) is a compendium
      of terms to define the diverse phenotypic characteristics of plant species,
      including plant anatomy, morphology, and development stages. Adoption of this
      highly useful ontology is limited, when compared to GO, because of the lack of
      user-friendly tools that enable the use of PO for statistical enrichment
      analysis. To address this challenge, we introduce Plant Ontology Enrichment
      Analysis Server (POEAS) in the public domain. POEAS uses a simple list of genes
      as input data and performs enrichment analysis using Ontologizer 2.0 to provide
      results in two levels, enrichment results and visualization utilities, to
      generate ontological graphs that are of publication quality. POEAS also offers
      interactive options to identify user-defined background population sets, various
      multiple-testing correction methods, different enrichment calculation methods,
      and resampling tests to improve statistical significance. The availability of
      such a tool to perform phenomic enrichment analyses using plant genes as a
      complementary resource will permit the adoption of PO-based phenomic analysis as
      part of analytical workflows. POEAS can be accessed using the URL
      http://caps.ncbs.res.in/poeas. 

PMID- 25574138
TI  - An evaluation of welding processes to reduce hexavalent chromium exposures and
      reduce costs by using better welding techniques.
AB  - A group of stainless steel arc welding processes was compared for emission rates
      of fume and hexavalent chromium, and costs per meter length of weld. The
      objective was to identify those with minimal emissions and also compare relative
      labor and consumables costs. The selection included flux-cored arc welding
      (FCAW), shielded-metal arc welding (SMAW), and multiple gas metal arc welding
      (GMAW) processes. Using a conical chamber, fumes were collected, and fume
      generation rates and hexavalent chromium (Cr(6+)) were measured. GMAW processes
      used were short-circuit (SC) and pulsed-spray modes. Flux-cored welding used gas
      shielding. Costs were estimated per meter of a 6.3-mm thick horizontal butt weld.
      Emission rates of Cr(6+) were lowest for GMAW processes and highest for SMAW;
      several GMAW processes had less than 2% of the SMAW generation rate. Labor and
      consumable costs for the processes studied were again highest for SMAW, with
      those of several GMAW types about half that cost. The results show that use of
      any of the GMAW processes (and flux-cored welding) could substantially reduce
      fume and Cr(6+) emissions, and greatly reduce costs relative to SMAW. 

PMID- 25574137
TI  - Investigation of Fat Metabolism during Antiobesity Interventions by Magnetic
      Resonance Imaging and Spectroscopy.
AB  - The focus of current treatments for obesity is to reduce the body weight or
      visceral fat, which requires longer duration to show effect. In this study, we
      investigated the short-term changes in fat metabolism in liver, abdomen, and
      skeletal muscle during antiobesity interventions including Sibutra mine treatment
      and diet restriction in obese rats using magnetic resonance imaging, magnetic
      resonance spectroscopy, and blood chemistry. Sibutramine is an antiobesity drug
      that results in weight loss by increasing satiety and energy expenditure. The
      Sibutramine-treated rats showed reduction of liver fat and intramyocellular
      lipids on day 3. The triglycerides (TG) decreased on day 1 and 3 compared to
      baseline (day 0). The early response/nonresponse in different fat depots will
      permit optimization of treatment for better clinical outcome rather than staying
      with a drug for longer periods. 

PMID- 25574140
TI  - Investigations of Koutango Virus Infectivity and Dissemination Dynamics in Aedes
      aegypti Mosquitoes.
AB  - Aedes aegypti has already been implicated in the emergence of dengue and
      chikungunya viruses in the southern US. Vector competence is the ability of a
      mosquito species to support transmission of an arbovirus, which is bounded by its
      ability to support replication and dissemination of the virus through the
      mosquito body to the salivary glands to be expectorated in the saliva at the time
      of feeding on a vertebrate host. Here, we investigate the vector competence of A.
      aegypti for the arbovirus koutango by orally challenging mosquitoes with two
      titers of virus. We calculated the effective vector competence, a cumulative
      measure of transmission capability weighted by mosquito survival, and determined
      that A. aegypti was competent at the higher dose only. We conclude that further
      investigation is needed to determine the infectiousness of vertebrate hosts to
      fully assess the emergence potential of this virus in areas rich in A. aegypti. 

PMID- 25574141
TI  - Emergency mosquito control on a selected area in eastern north Carolina after
      hurricane irene.
AB  - Natural disasters such as hurricanes may contribute to mosquito abundance and,
      consequently, arbovirus transmission risk. In 2011, flooding from Hurricane Irene
      in eastern North Carolina (NC) resulted in increased mosquito populations that
      hindered recovery efforts. Budget shortfalls in NC have reduced the functionality
      of long-term mosquito surveillance and control programs; hence, many counties
      rely on the Federal Emergency Management Agency for post-disaster mosquito
      control. This pilot study examines mosquito abundance pre- and post-aerial
      insecticide spraying at eight study sites in Washington and Tyrrell Counties in
      rural eastern NC after Hurricane Irene. Percent change was calculated and
      compared for traps in areas that received aerial pesticide application and those
      that did not. Traps in spray zones show decreases in mosquito abundance when
      compared to control traps (treatment: -52.93%; control: 3.55%), although no
      significant differences (P = 0.286) were found in mosquito abundance between
      groups. Implications of reactive rather than proactive mosquito control responses
      are discussed. 

PMID- 25574139
TI  - Potential health effects associated with dermal exposure to occupational
      chemicals.
AB  - There are a large number of workers in the United States, spanning a variety of
      occupational industries and sectors, who are potentially exposed to chemicals
      that can be absorbed through the skin. Occupational skin exposures can result in
      numerous diseases that can adversely affect an individual's health and capacity
      to perform at work. In general, there are three types of chemical-skin
      interactions of concern: direct skin effects, immune-mediated skin effects, and
      systemic effects. While hundreds of chemicals (metals, epoxy and acrylic resins,
      rubber additives, and chemical intermediates) present in virtually every industry
      have been identified to cause direct and immune-mediated effects such as contact
      dermatitis or urticaria, less is known about the number and types of chemicals
      contributing to systemic effects. In an attempt to raise awareness, skin notation
      assignments communicate the potential for dermal absorption; however, there is a
      need for standardization among agencies to communicate an accurate description of
      occupational hazards. Studies have suggested that exposure to complex mixtures,
      excessive hand washing, use of hand sanitizers, high frequency of wet work, and
      environmental or other factors may enhance penetration and stimulate other
      biological responses altering the outcomes of dermal chemical exposure.
      Understanding the hazards of dermal exposure is essential for the proper
      implementation of protective measures to ensure worker safety and health. 

PMID- 25574142
TI  - Environmental changes can produce shifts in chagas disease infection risk.
AB  - An epidemiological network contains all the organisms involved (types) in the
      transmission of a parasite. The nodes of the network represent reservoirs, hosts,
      and vectors, while the links between the nodes represent the strength and
      direction of parasite movement. Networks that contain humans are of special
      interest because they are of concern to public health authorities. Under these
      circumstances, it is possible, in principle, to identify cycles (closed paths in
      the network) that include humans and select the ones that carry the maximum
      probability of human infection. The basic reproduction number R 0 in such a
      network gives the average number of new infections of any type after the
      introduction of one individual infected by any type. To obtain R 0 for complex
      networks, one can use the next-generation matrix (NGM) approach. Every entry in
      NGM will average the contribution of each link that connects two types. To tease
      the contribution of every cycle apart, we define the virulence as the geometric
      mean of the NGM entries corresponding to the links therein. This approach allows
      for the quantification of specific cycles of interest while it also makes the
      computation of the sensitivity and elasticity of the parameters easier. In this
      work, we compute the virulence for the transmission dynamics of Chagas disease
      for a typical rural area in Colombia incorporating the effect of environmental
      changes on the vector population size. We concluded that the highest contribution
      to human infection comes from humans themselves, which is a surprising and
      interesting result. In addition, sensitivity analysis revealed that increasing
      vector population size increases the risk of human infection. 

PMID- 25574143
TI  - Kissing bugs in the United States: risk for vector-borne disease in humans.
AB  - Eleven species of kissing bugs are found in the United States. Their home ranges
      may be expanding northward, perhaps as a consequence of climate change. At least
      eight of the species, perhaps all, are reported to harbor Trypanosoma cruzi, the
      parasite that causes Chagas disease. Because humans are encroaching on kissing
      bug habitat, there is concern for vector-transmitted Chagas disease in the United
      States. To date, documented autochthonous cases of Chagas in humans in the United
      States are rare. Kissing bugs are capable of adapting to new habitats such as
      human domiciles; however, they do not colonize homes in the United States as in
      Central and South America. We review the biology, behavior, and medical
      importance of kissing bugs and the risk they pose for transmission of Chagas
      disease in the United States. Where possible, descriptions of US species are
      compared to the epidemiologically important Latin American species. 

PMID- 25574144
TI  - An 8-Week Knee Osteoarthritis Treatment Program of Hyaluronic Acid Injection,
      Deliberate Physical Rehabilitation, and Patient Education is Cost Effective at 2
      Years Follow-up: The OsteoArthritis Centers of America(SM) Experience.
AB  - Numerous nonsurgical interventions have been reported to improve symptoms of knee
      osteoarthritis (OA) over the short term. However, longer follow-up is required to
      accurately characterize outcomes such as cost effectiveness and delayed
      arthroplasty. A total of 553 patients with symptomatic knee OA who previously
      underwent a single 8-week multimodal treatment program were contacted at 1 year
      (n = 336) or 2 years (n = 217) follow-up. The percentage of patients who
      underwent knee arthroplasty was 10% at 1 year and 18% at 2 years following
      program completion. The treatment program was highly cost effective at $12,800
      per quality-adjusted life year at 2 years. Cost effectiveness was maintained
      under a variety of plausible assumptions and regardless of gender, age, body mass
      index, disease severity, or knee pain severity. In summary, a single 8-week
      multimodal knee OA treatment program is cost effective and may lower knee
      arthroplasty utilization through 2 years follow-up. 

PMID- 25574145
TI  - Endovascular treatment of aneurysms of the popliteal artery by a covered
      endoprosthesis.
AB  - PURPOSE: The current gold standard of popliteal artery aneurysm (PAA) treatment
      is saphenous vein bypass grafting. The aim of this retrospective single-center
      study is to investigate the safety and efficacy in the treatment of PAA by an
      endovascular implanted covered endoprosthesis. MATERIALS AND METHODS: Ten
      patients, mean age 64.6 (range, 52-78) years, with PAA were treated with an
      expanded Polytetrafluoroethylen (ePTFE)-covered stent graft (Viabahn((r)), W.L.
      Gore and Associates Inc, Flagstaff, AZ, USA). In median, 1.4 prostheses were
      implanted with a median length of 180 mm. Follow-up visits included determination
      of ankle-brachial index (ABI) and color-coded duplex sonography. RESULTS: The
      technical success rate was 100% (10/10). Clinically, there was an increase in ABI
      from 0.62 +/- 0.17 to 0.91 +/- 0.15 postinterventionally and to 0.89 +/- 0.16
      after an average follow-up of 24.7 months. During the follow-up period, 2 (20%)
      stent occlusions occurred; both of them were treated with a bypass graft.
      CONCLUSION: The treatment of PAA with covered endoprosthesis is a safe and
      effective alternative to open surgical therapy, where open surgical therapy is
      contraindicated or patient refused open surgery.

PMID- 25574146
TI  - Antioxidant beverages: green tea intake and coronary artery disease.
AB  - Coronary artery disease (CAD) is recognized as an inflammatory disease. In the
      present study, we investigated the effect of green tea consumption on plasma
      inflammatory markers and the association between green tea consumption and CAD.
      In 22 healthy volunteers, green tea consumption (7 cups/day) significantly
      decreased serum malondialdehyde-modified low-density lipoprotein (MDA-LDL)
      concentrations, whereas green tea consumption tended to decrease plasma C
      reactive protein and interleukin (IL)-6 concentrations. In 725 patients
      undergoing coronary angiography, the percentage of patients drinking <1 cup/day
      of green tea was higher in patients with myocardial infarction (MI) than in CAD
      patients without MI and patients without CAD (29% vs. 15% and 18%, P < 0.01).
      Green tea consumption was found to be inversely associated with MI in Japanese
      patients. The protective effect of green tea against atherosclerosis is more
      likely to be because of the inhibitory effect of LDL oxidation than because of
      anti-inflammatory effect. 

PMID- 25574147
TI  - Changes in protein level in the cerebrospinal fluid of a patient with cerebral
      radiation necrosis treated with bevacizumab.
AB  - A 32-year-old woman underwent surgeries and radiation therapy for astrocytoma.
      She developed symptomatic radiation necrosis in the lesion, which caused
      hydrocephalus. She initially underwent ventricular drainage, because the protein
      level in the cerebrospinal fluid (CSF) was 787 mg/dL, which was too high for
      shunt surgery. Because she also had breast cancer, which was pathologically
      diagnosed as an invasive ductal carcinoma, standard bevacizumab therapy in
      combination with paclitaxel every 2 weeks was selected. Interestingly, after 2
      days, the agents had dramatically reduced the CSF protein level. However, it
      returned to approximately the initial level within 2 weeks. After two courses of
      this regimen, a ventriculoperitoneal shunt was placed. After 10 courses of this
      regimen, the CSF protein level decreased to 338 mg/dL, which is less than half of
      the initial level. Long-term administration of bevacizumab might decrease leakage
      of protein from the vessels around the ventriculus. 

PMID- 25574148
TI  - Clinicians' expectations for gene-driven cancer therapy.
AB  - A new era of medicine is rapidly approaching, which will change not only
      pathological diagnosis but also medical decision-making. This paper raises the
      question of how well prepared doctors are to address the new issues that will
      soon confront them. The human genome has been completely sequenced and general
      understanding about cancer biology has increased enormously with understanding
      that unregulated gene function and complicated changes in signal pathways are
      related to uncontrolled cell growth. Thus, gene-driven therapy involving
      alterations to genes are recognized to present new therapy options. This advance
      will necessitate major changes to the decision-making aspect of physicians. This
      article focuses on defining the pertinent changes and addressing what they mean
      for practicing physicians. 

PMID- 25574149
TI  - Creation and Validation of the Self-esteem/Self-image Female Sexuality (SESIFS)
      Questionnaire.
AB  - INTRODUCTION: Self-esteem and self-image are psychological aspects that affect
      sexual function. AIMS: To validate a new measurement tool that correlates the
      concepts of self-esteem, self-image, and sexuality. METHODS: A 20-question test
      (the self-esteem/self-image female sexuality [SESIFS] questionnaire) was created
      and tested on 208 women. Participants answered: Rosenberg's self-esteem scale,
      the female sexual quotient (FSQ), and the SESIFS questionnaire. Pearson's
      correlation coefficient was used to test concurrent validity of the SESIFS
      against Rosenberg's self-esteem scale and the FSQ. Reliability was tested using
      the Cronbach's alpha coefficient. RESULT: The new questionnaire had a good
      overall reliability (Cronbach's alpha r = 0.862, p < 0.001), but the sexual
      domain scored lower than expected (r = 0.65). The validity was good: overall
      score r = 0.38, p < 0.001, self-esteem domain r = 0.32, p < 0.001, self-image
      domain r = 0.31, p < 0.001, sexual domain r = 0.29, p < 0.001. CONCLUSIONS: The
      SESIFS questionnaire has limitations in measuring the correlation among self
      esteem, self-image, and sexuality domains. A new, revised version is being tested
      and will be presented in an upcoming publication.

PMID- 25574150
TI  - Clinical Assessment of Tribulus terrestris Extract in the Treatment of Female
      Sexual Dysfunction.
AB  - This is a qualitative-quantitative study based on hospital records of female
      patients of reproductive age, presenting sexual dysfunction, and treated with 250
      mg Tribulus terrestris extract (1 tablet thrice daily for 90 days). Safety
      monitoring included vital signs, physical examination, laboratory tests, and
      occurrence of adverse events. Efficacy analysis included results of the Female
      Sexual Function Index (FSFI), dehydroepiandrosterone (DHEA) levels together with
      total and free testosterone, and the patient and physician assessments. There was
      a statistically significant improvement in total FSFI scores (P < 0.0001) post
      treatment, with improvement among 106 (88.33%) subjects. There was a
      statistically significant (P < 0.0001) increase in the level of DHEA, while the
      levels of both serum testosterone (P = 0.284) and free testosterone decreased (P
      < 0.0001). Most adverse events recorded were related to the gastrointestinal
      tract. Physical examination showed no significant changes post-treatment. Based
      on the results, it is concluded that the T. terrestris extract is safe and
      effective in the treatment of female sexual dysfunction. 

PMID- 25574151
TI  - Time-resolved Characterization of Particle Associated Polycyclic Aromatic
      Hydrocarbons using a newly-developed Sequential Spot Sampler with Automated
      Extraction and Analysis.
AB  - A versatile and compact sampling system, the Sequential Spot Sampler (S3) has
      been developed for pre-concentrated, time-resolved, dry collection of fine and
      ultrafine particles. Using a temperature-moderated laminar flow water
      condensation method, ambient particles as small as 6 nm are deposited within a
      dry, 1-mm diameter spot. Sequential samples are collected on a multiwell plate.
      Chemical analyses are laboratory-based, but automated. The sample preparation,
      extraction and chemical analysis steps are all handled through a commercially
      available, needle-based autosampler coupled to a liquid chromatography system.
      This automation is enabled by the small deposition area of the collection. The
      entire sample is extracted into 50-100MUl volume of solvent, providing
      quantifiable samples with small collected air volumes. A pair of S3 units was
      deployed in Stockton (CA) from November 2011 to February 2012. PM2.5 samples were
      collected every 12 hrs, and analyzed for polycyclic aromatic hydrocarbons (PAHs).
      In parallel, conventional filter samples were collected for 48 hrs and used to
      assess the new system's performance. An automated sample preparation and
      extraction was developed for samples collected using the S3. Collocated data from
      the two sequential spot samplers were highly correlated for all measured
      compounds, with a regression slope of 1.1 and r2=0.9 for all measured
      concentrations. S3/filter ratios for the mean concentration of each individual
      PAH vary between 0.82 and 1.33, with the larger variability observed for the
      semivolatile components. Ratio for total PAH concentrations was 1.08. Total PAH
      concentrations showed similar temporal trend as ambient PM2.5 concentrations.
      Source apportionment analysis estimated a significant contribution of biomass
      burning to ambient PAH concentrations during winter.

PMID- 25574152
TI  - Quantile Regression Adjusting for Dependent Censoring from Semi-Competing Risks.
AB  - In this work, we study quantile regression when the response is an event time
      subject to potentially dependent censoring. We consider the semi-competing risks
      setting, where time to censoring remains observable after the occurrence of the
      event of interest. While such a scenario frequently arises in biomedical studies,
      most of current quantile regression methods for censored data are not applicable
      because they generally require the censoring time and the event time be
      independent. By imposing rather mild assumptions on the association structure
      between the time-to-event response and the censoring time variable, we propose
      quantile regression procedures, which allow us to garner a comprehensive view of
      the covariate effects on the event time outcome as well as to examine the
      informativeness of censoring. An efficient and stable algorithm is provided for
      implementing the new method. We establish the asymptotic properties of the
      resulting estimators including uniform consistency and weak convergence. The
      theoretical development may serve as a useful template for addressing estimating
      settings that involve stochastic integrals. Extensive simulation studies suggest
      that the proposed method performs well with moderate sample sizes. We illustrate
      the practical utility of our proposals through an application to a bone marrow
      transplant trial.

PMID- 25574153
TI  - Prosody in a communication system developed without a language model.
AB  - Prosody, he "music" of language, is an important aspect of all natural languages,
      spoken and signed. We ask here whether prosody is also robust across learning
      conditions. If a child were not exposed to a conventional language and had to
      construct his own communication system, would that system contain prosodic
      structure? We address this question by observing a deaf child who received no
      sign language input and whose hearing loss prevented him from acquiring spoken
      language. Despite his lack of a conventional language model, this child developed
      his own gestural system. In this system, features known to mark phrase and
      utterance boundaries in established sign languages were used to consistently mark
      the ends of utterances, but not to mark phrase or utterance internal boundaries.
      A single child can thus develop the seeds of a prosodic system, but full
      elaboration may require more time, more users, or even more generations to
      blossom.

PMID- 25574155
TI  - Facial neuropathy with imaging enhancement of the facial nerve: a case report.
AB  - A young women developed unilateral facial neuropathy 2 weeks after a motor
      vehicle collision involving fractures of the skull and mandible. MRI showed
      contrast enhancement of the facial nerve. We review the literature describing
      facial neuropathy after trauma and facial nerve enhancement patterns with
      different causes of facial neuropathy.

PMID- 25574154
TI  - Biosynthetically Distinct Cytotoxic Polyketides from Setophoma terrestris.
AB  - Sixteen polyketides belonging to diverse structural classes, including
      monomeric/dimeric tetrahydroxanthones and resorcylic acid lactones, were isolated
      from an organic extract of a fungal culture Setophoma terrestris (MSX45109) using
      bioactivity-directed fractionation as part of a search for anticancer leads from
      filamentous fungi. Of these, six were new: penicillixanthone B (5), blennolide H
      (6), 11-deoxy blennolide D (7), blennolide I (9), blennolide J (10), and
      pyrenomycin (16). The known compounds were: secalonic acid A (1), secalonic acid
      E (2), secalonic acid G (3), penicillixanthone A (4), paecilin B (8),
      aigialomycin A (11), hypothemycin (12), dihydrohypothemycin (13), pyrenochaetic
      acid C (14), and nidulalin B (15). The structures were elucidated using a set of
      spectroscopic and spectrometric techniques; the absolute configurations of
      compounds 1-10 were determined using ECD spectroscopy combined with time
      dependent density functional theory (TDDFT) calculations, while a modified
      Mosher's ester method was used for compound 16. The cytotoxic activities of
      compounds (1-15) were evaluated using the MDA-MB-435 (melanoma) and SW-620
      (colon) cancer cell lines. Compounds 1, 4, and 12 were the most potent with IC50
      values ranging from 0.16 to 2.14 MUM. When tested against a panel of bacteria and
      fungi, compounds 3 and 5 showed promising activity against the Gram-positive
      bacterium Micrococcus luteus with MIC values of 5 and 15 MUg/mL, respectively.

PMID- 25574156
TI  - The relation between reactivity at 4 months and Behavioral Inhibition in the
      second year: Replication Across Three Independent Samples.
AB  - This paper examines the predictive relations between two infant temperamental
      biases assessed at 4 months and inhibited behavior during the first two years of
      life in three independent samples from two research laboratories. Although each
      sample used slightly different criteria for classifying infants, the results
      across samples were consistent. Infants of both genders who displayed high levels
      of motor activity and distress to unfamiliar events were more inhibited at 14
      months of age. By 24 months there were significant sex differences: boys
      identified as high reactive were more inhibited than high reactive girls.

PMID- 25574157
TI  - Transferable Force Field for Metal-Organic Frameworks from First-Principles: BTW
      FF.
AB  - We present an ab-initio derived force field to describe the structural and
      mechanical properties of metal-organic frameworks (or coordination polymers). The
      aim is a transferable interatomic potential that can be applied to MOFs
      regardless of metal or ligand identity. The initial parametrization set includes
      MOF-5, IRMOF-10, IRMOF-14, UiO-66, UiO-67, and HKUST-1. The force field describes
      the periodic crystal and considers effective atomic charges based on topological
      analysis of the Bloch states of the extended materials. Transferable potentials
      were developed for the four organic ligands comprising the test set and for the
      associated Cu, Zn, and Zr metal nodes. The predicted materials properties,
      including bulk moduli and vibrational frequencies, are in agreement with explicit
      density functional theory calculations. The modal heat capacity and lattice
      thermal expansion are also predicted.

PMID- 25574159
TI  - Risk evaluation of bogie system based on extension theory and entropy weight
      method.
AB  - A bogie system is the key equipment of railway vehicles. Rigorous practical
      evaluation of bogies is still a challenge. Presently, there is overreliance on
      part-specific experiments in practice. In the present work, a risk evaluation
      index system of a bogie system has been established based on the inspection data
      and experts' evaluation. Then, considering quantitative and qualitative aspects,
      the risk state of a bogie system has been evaluated using an extension theory and
      an entropy weight method. Finally, the method has been used to assess the bogie
      system of four different samples. Results show that this method can assess the
      risk state of a bogie system exactly. 

PMID- 25574160
TI  - Estimation of critical gap based on Raff's definition.
AB  - Critical gap is an important parameter used to calculate the capacity and delay
      of minor road in gap acceptance theory of unsignalized intersections. At an
      unsignalized intersection with two one-way traffic flows, it is assumed that two
      events are independent between vehicles' arrival of major stream and vehicles'
      arrival of minor stream. The headways of major stream follow M3 distribution.
      Based on Raff's definition of critical gap, two calculation models are derived,
      which are named M3 definition model and revised Raff's model. Both models use
      total rejected coefficient. Different calculation models are compared by
      simulation and new models are found to be valid. The conclusion reveals that M3
      definition model is simple and valid. Revised Raff's model strictly obeys the
      definition of Raff's critical gap and its application field is more extensive
      than Raff's model. It can get a more accurate result than the former Raff's
      model. The M3 definition model and revised Raff's model can derive accordant
      result. 

PMID- 25574158
TI  - Histone Demethylases in Colon Cancer.
AB  - Cell growth and proliferation are controlled through different posttranslational
      modifications including demethylation, a process regulated by regulated by the
      demethylase enzymes. This review focuses on our current understanding of
      functional and therapeutic potentials of histone demethylases in colon cancer.
      Colon cancer is the third most common malignancy worldwide and the second leading
      cause of cancer deaths in the United States. The key protein families responsible
      for demethylation of histones, histone demethylases, have emerged as new
      therapeutic targets in different cancer types including colon cancer. These
      families are of great interest as potential novel biomarkers for diagnosis and
      targets for therapy and prevention of colon cancer. In this manuscript, we will
      discuss our current understanding of the histone demethylase family, and the role
      they play as epigenetic activators or repressors of different genes in colon
      cancer.

PMID- 25574161
TI  - The Prevalence and Pattern of Superficial Fungal Infections among School Children
      in Ile-Ife, South-Western Nigeria.
AB  - Fungal infections of the skin and nails are common global problems with attendant
      morbidity among affected individuals. Children are mostly affected due to
      predisposing factors such as overcrowding and low socioeconomic factors. The aim
      of this study was to determine the prevalence and the clinical patterns of
      superficial fungal infections among primary school children in Ile-Ife. A
      multistage sampling was conducted to select eight hundred pupils from ten primary
      schools in Ile-Ife. Data on epidemiological characteristics and clinical history
      was collected using a semistructured questionnaire and skin scrapings were done.
      The prevalence of superficial fungal infections among the 800 respondents was
      35.0%. Male pupils constituted 51.0% of respondents while the females were 49.0%.
      The mean age for all the respondents was 9.42 +/- 2.00. Tinea capitis was the
      commonest infection with a prevalence of 26.9% and tinea unguium, tinea corporis,
      and tinea faciei had a prevalence of 0.8%, 0.6%, and 0.5%, respectively. Tinea
      manuum had the least prevalence of 0.1%. Pityriasis versicolor had a prevalence
      of 4.4%. Microsporum audouinii was the leading organism isolated. The study shows
      that the prevalence of superficial fungal infection (SFI) among primary school
      children in Ile-Ife is high with tinea capitis as the commonest SFI. 

PMID- 25574162
TI  - Hepatitis B e Antigen Seroconversion Is Related with the Function of Dendritic
      Cells in Chronic Hepatitis B Virus Infection.
AB  - Aim. To investigate the relationship between hepatitis B e antigen seroconversion
      and the function of dendritic cells (DC) in patients with hepatitis B virus.
      Methods. The peripheral blood mononuclear cells (PBMC) from 21 chronic HBV
      patients in immune tolerance state, 23 patients in inactive HBsAg carrier state,
      and 10 healthy HBV-naive blood donors were incubated and induced into DC in
      presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and
      interleukin-4 (IL-4), respectively. The expressions of surface markers on DC were
      detected by flow cytometry, and the stimulatory capacity of DC in allogenic mixed
      leukocyte reaction (MLR) was tested by CCK-8, and the level of cytokines released
      by DC was analyzed by enzyme-linked immunosorbent assay (ELISA). Results. DC from
      patients in immune tolerance showed a remarkably lower surface expression of
      CD80, CD86, and HLA-DR and exhibited an impaired stimulatory capacity in MLR and
      reduced secretion of IL-12, as compared to the patients in inactive HBsAg carrier
      state. There was no significant difference between the indicators from the
      patients in inactive HBsAg carrier state and healthy subjects. There was a
      significant difference of HBV DNA level between immune tolerance and inactive
      HBsAg carrier group (P < 0.01) and a negative correlation between HBV DNA level
      and the expressions of dendritic cells in both groups, respectively (P = 0.01).
      Conclusion. DC from patients in inactive HBsAg carrier state shows stronger
      function in comparison with patients in immune tolerance, the expressions of
      dendritic cells correlate with HBV DNA level, and the function stage of DC may
      play an important role in HBeAg seroconversion. 

PMID- 25574163
TI  - Transcutaneous intraluminal impedance measurement for minimally invasive
      monitoring of gastric motility: validation in acute canine models.
AB  - Transcutaneous intraluminal impedance measurement (TIIM) is a new method to
      cutaneously measure gastric contractions by assessing the attenuation dynamics of
      a small oscillating voltage emitted by a battery-powered ingestible capsule
      retained in the stomach. In the present study, we investigated whether TIIM can
      reliably assess gastric motility in acute canine models. Methods. Eight mongrel
      dogs were randomly divided into 2 groups: half received an active TIIM pill and
      half received an identically sized sham capsule. After 24-hour fasting and
      transoral administration of the pill (active or sham), two force transducers (FT)
      were sutured onto the antral serosa at laparotomy. After closure, three standard
      cutaneous electrodes were placed on the abdomen, registering the transluminally
      emitted voltage. Thirty-minute baseline recordings were followed by
      pharmacological induction of gastric contractions using neostigmine IV and
      another 30-minute recording. Normalized one-minute baseline and post-neostigmine
      gastric motility indices (GMIs) were calculated and Pearson correlation
      coefficients (PCCs) between cutaneous and FT GMIs were obtained. Statistically
      significant GMI PCCs were seen in both baseline and post-neostigmine states.
      There were no significant GMI PCCs in the sham capsule test. Further chronic
      animal studies of this novel long-term gastric motility measurement technique are
      needed before testing it on humans. 

PMID- 25574164
TI  - Dietary Factors in Relation to Helicobacter pylori Infection.
AB  - Background and Aim. Helicobacter pylori (HP) and diet are both risk factors for
      gastric cancer. The aim of this study was to evaluate the Helicobacter pylori
      infection and dietary habits common in Khuzestan province. Methods. This cross
      sectional study was conducted in 2011-2013 on 374 patients. Participants were
      interviewed using a food frequency questionnaire and tissue sample of the antrum
      was sent for pathology lab. The histopathological major variables were graded on
      a scale of 3 (mild, moderate, and severe) and data analyzed using nonparametric
      tests. Results. In this study, of 160 patients (43%) that were determined, 8.1
      percent had severe contamination. Among dietary patterns, relationship between
      energy intake and carbohydrate with H. pylori was significant. A direct
      association was found between mean daily intakes of sausage (P = 0.001) and
      burgers (P < 0.05) with HP infection. Low intake of fresh vegetables and fruits
      was the most significant risk factors (P < 0.05). Conclusion. There is a
      possibility that some dietary factors such as consumption of fast foods and low
      intake of fresh vegetables may increase the chance of HP and severity of this
      infection. 

PMID- 25574165
TI  - Feasibility and Acceptability of Utilizing a Smartphone Based Application to
      Monitor Outpatient Discharge Instruction Compliance in Cardiac Disease Patients
      around Discharge from Hospitalization.
AB  - The purpose of this study was to determine the feasibility and acceptability of
      utilizing a smartphone based application to monitor compliance in patients with
      cardiac disease around discharge. For 60 days after discharge, patients'
      medication compliance, physical activity, follow-up care, symptoms, and reading
      of education material were monitored daily with the application. 16 patients were
      enrolled in the study (12 males, 4 females, age 55 +/- 18 years) during their
      hospital stay. Five participants were rehospitalized during the study and did not
      use the application once discharged. Seven participants completed 1-30 days and
      four patients completed >31 days. For those 11 patients, medication reminders
      were utilized 37% (1-30-day group) and 53% (>31-day group) of the time, education
      material was read 44% (1-30) and 53% (>31) of the time, and physical activity was
      reported 25% (1-30) and 42% (>31) of the time. Findings demonstrated that
      patients with stable health utilized the application, even if only minimally.
      Patients with decreased breath sounds by physical exam and who reported their
      health as fair to poor on the day of discharge were less likely to utilize the
      application. Acceptability of the application to report health status varied
      among the stable patients. 

PMID- 25574167
TI  - Selenium supplementation for autoimmune thyroiditis: a systematic review and meta
      analysis.
AB  - Many studies have reported that selenium (Se) has a close relationship with
      autoimmune thyroiditis (AIT). The therapeutic effect of Se supplementation in AIT
      treatment remains unclear. The objective of the present study was to determine
      the efficacy of Se supplementation for the treatment of AIT. A structured
      literature search was undertaken to identify all randomized controlled trials
      conducted in patients with AIT receiving Se supplementation or placebo. Nine
      studies enrolling a total of 787 patients were included. The results showed that
      Se supplementation with duration 6 months significantly dropped the TPOAb titers
      but did not decrease the TgAb titers. Patients assigned to Se supplementation for
      12-month duration showed significantly lower TPOAb titers and TgAb titers.
      Patients after Se supplementation had a higher chance to improve the mood or well
      being compared with controls. Se supplementation is associated with a significant
      decrease in TPOAb titers at 6 and 12 months; meanwhile, the TgAb titers can be
      dropped at 12 months. After Se supplementation treatment, patients had a higher
      chance to improve the mood without significant adverse events. 

PMID- 25574166
TI  - Waist-to-Height Ratio Is a Better Anthropometric Index than Waist Circumference
      and BMI in Predicting Metabolic Syndrome among Obese Mexican Adolescents.
AB  - Objective. To identify the degree of association between anthropometric indices
      and components of metabolic syndrome (MS) and to determine optimal cut-off points
      of these indices for predicting MS in obese adolescents. Methods. A cross
      sectional study with a sample of (n = 110) Mexican obese adolescents grouped by
      sex and the presence/absence of MS. BMI percentile, waist circumference (WC), and
      waist-to-height ratio (WHtR) were tested. ROC curves of the anthropometric
      indices were created to identify whether an index was a significant predictor of
      MS. Results. BMI percentile, WC, and WHtR were significantly correlated with
      systolic and diastolic blood pressure. As predictors of MS overall patients, the
      BMI percentile generated an area under curve (AUC) of 0.651 (P = 0.008), cut-off
      point above the 99th percentile. WC generated an AUC of 0.704 (P < 0.001), cut
      off point of >=90 cm. WHtR demonstrated an AUC of 0.652 (P = 0.008), cut-off
      point of 0.60. WHtR >=0.62 and WHtR >=0.61 generate AUC of 0.737 (P = 0.006) and
      AUC of 0.717 (P = 0.014) for predicting hypertension and insulin resistance,
      respectively, in females. Conclusion. WHtR is a better tool than WC and BMI for
      identifying cardiometabolic risk. The overall criterion (WHtR >= 0.6) could be
      appropriate for predicting MS in obese Mexican adolescents. 

PMID- 25574169
TI  - Detection of influenza virus infection using two PCR methods.
AB  - Rapid, accurate, and cost-effective methods to identify the cause of respiratory
      tract infections are needed to maximize clinical benefit. Outpatients with acute
      respiratory illness were tested for influenza using a singleplex reverse
      transcriptase polymerase chain reaction (SRT-PCR) method. A multiplex RT-PCR (MRT
      PCR) method tested for influenza and 17 other viruses and was compared with SRT
      PCR using chi-square tests. Among 935 patients, 335 (36%) tested positive for
      influenza A and influenza B using SRT-PCR. Using MRT-PCR, 320 (34.2%) tested
      positive for influenza A and influenza B. This study supports MRT-PCR as a
      comparable method for detecting influenza among patients seeking outpatient care
      for acute respiratory illnesses. 

PMID- 25574168
TI  - Phosphoglycerate dehydrogenase: potential therapeutic target and putative
      metabolic oncogene.
AB  - Exemplified by cancer cells' preference for glycolysis, for example, the Warburg
      effect, altered metabolism in tumorigenesis has emerged as an important aspect of
      cancer in the past 10-20 years. Whether due to changes in regulatory tumor
      suppressors/oncogenes or by acting as metabolic oncogenes themselves, enzymes
      involved in the complex network of metabolic pathways are being studied to
      understand their role and assess their utility as therapeutic targets. Conversion
      of glycolytic intermediate 3-phosphoglycerate into phosphohydroxypyruvate by the
      enzyme phosphoglycerate dehydrogenase (PHGDH)-a rate-limiting step in the
      conversion of 3-phosphoglycerate to serine-represents one such mechanism.
      Forgotten since classic animal studies in the 1980s, the role of PHGDH as a
      potential therapeutic target and putative metabolic oncogene has recently
      reemerged following publication of two prominent papers near-simultaneously in
      2011. Since that time, numerous studies and a host of metabolic explanations have
      been put forward in an attempt to understand the results observed. In this paper,
      I review the historic progression of our understanding of the role of PHGDH in
      cancer from the early work by Snell through its reemergence and rise to
      prominence, culminating in an assessment of subsequent work and what it means for
      the future of PHGDH. 

PMID- 25574170
TI  - Effect of surface treated silicon dioxide nanoparticles on some mechanical
      properties of maxillofacial silicone elastomer.
AB  - Current materials used for maxillofacial prostheses are far from ideal and there
      is a need for novel improved materials which mimic as close as possible the
      natural behavior of facial soft tissues. This study aimed to evaluate the effect
      of adding different concentrations of surface treated silicon dioxide
      nanoparticles (SiO2) on clinically important mechanical properties of a
      maxillofacial silicone elastomer. 147 specimens of the silicone elastomer were
      prepared and divided into seven groups (n = 21). One control group was prepared
      without nanoparticles and six study groups with different concentrations of
      nanoparticles, from 0.5% to 3% by weight. Specimens were tested for tear strength
      (ASTM D624), tensile strength (ASTM D412), percent elongation, and shore A
      hardness. SEM was used to assess the dispersion of nano-SiO2 within the elastomer
      matrix. Data were analyzed by one-way ANOVA and Scheffe test (alpha = 0.05).
      Results revealed significant improvement in all mechanical properties tested, as
      the concentration of the nanoparticles increased. This was supported by the
      results of the SEM. Hence, it can be concluded that the incorporation of surface
      treated SiO2 nanoparticles at concentration of 3% enhanced the overall mechanical
      properties of A-2186 silicone elastomer. 

PMID- 25574171
TI  - Microbiological Analysis of Surfaces of Leonardo Da Vinci's Atlantic Codex:
      Biodeterioration Risk.
AB  - Following the discovery of discoloration on some pages of the Atlantic Codex (AC)
      of Leonardo da Vinci kept in the Biblioteca Ambrosiana in Milan, some
      investigations have been carried out to verify the presence of microorganisms,
      such as bacteria and fungi. To verify the presence of microorganisms a
      noninvasive method of sampling has been used that was efficient and allowed us to
      highlight the microbial facies of the material that was examined using
      conventional microbiological techniques. The microclimatic conditions in the
      storage room as well as the water content of the volume were also assessed. The
      combined observations allowed the conclusion that the discoloration of suspected
      biological origin on some pages of AC is not related to the presence or current
      attack of microbial agents. 

PMID- 25574172
TI  - Process evaluation of workplace interventions with physical exercise to reduce
      musculoskeletal disorders.
AB  - Process evaluation is important to explain success or failure of workplace
      interventions. This study performs a summative process evaluation of workplace
      interventions with physical exercise. As part of a randomized controlled trial
      132 office workers with neck and shoulder pain were to participate in 10 weeks of
      elastic resistance training five times a week at the workplace; the 2 min group
      performed a single set of lateral raise to failure, and the 12 min group
      performed 5-6 sets with 8-12 repetitions. Participants received a single
      instructional session together with a training diary and manual at baseline (100%
      dose delivered and 100% dose received), and 59 and 57 participants, respectively,
      replied to the process evaluation questionnaire at 10-week follow-up. Results
      showed that in the 2 and 12 min groups, respectively, 82% and 81% of the
      participants completed more than 30 training sessions. However, two-thirds of the
      participants would have preferred more than a single exercise to vary between. In
      the 12 versus 2 min group more participants experienced the training sessions as
      too long (30% versus 5%). Most participants (67-92%) found the training diary and
      manual helpful, adequacy in a single instructional session, and satisfaction with
      the type of training. Among those with low adherence, lack of time (51%) and
      difficulties in starting exercising after illness (26%) were common barriers for
      regular training. Among those with low adherence, 52% felt that five training
      sessions per week were too much, and 29% would rather have trained a completely
      different kind of exercise. In conclusion, resistance training at the workplace
      is generally well received among office workers with neck-shoulder pain, but a
      one-size-fits-all approach is not feasible for all employees. 

PMID- 25574173
TI  - Toxic Anterior Segment Syndrome following Phacoemulsification Secondary to
      Overdose of Intracameral Gentamicin.
AB  - Objective. To report a case of toxic anterior segment syndrome (TASS) that was
      caused by inadvertent anterior chamber and cornea stromal injection with high
      dose gentamicin following cataract surgery. Methods. Case report. Results. We
      report a 72-year-old female patient who developed TASS that was caused by high
      dose gentamicin (20 mg/0.5 mL), which was inadvertently used during the formation
      of the anterior chamber and hydration of the corneal incision. Unlike previous
      cases, hyphema and hemorrhagic fibrinous reaction were seen in the anterior
      chamber. Despite treatment, bullous keratopathy developed and penetrating
      keratoplasty was performed. The excised corneal button was sent for
      histopathological examination. Conclusions. Subconjunctival gentamicin is highly
      toxic to the corneal endothelium and anterior chamber structures. Including it on
      the surgical table carries a potentially serious risk for contamination of the
      anterior chamber. 

PMID- 25574174
TI  - Kikuchi-fujimoto disease: a rare cause of Fever in the returning traveller.
AB  - Background. Kikuchi-Fujimoto disease (KFD) is typically a self-limited, benign
      illness which presents with fever and lymphadenopathy. It is rare in Caucasians,
      normally occurring in those of Asian descent. The aetiology is poorly understood,
      but it appears to be an autoimmune disorder with a possible infectious trigger.
      The clinical features are such that it is often mistaken for infectious diseases
      or malignancy. Case Report. Here we describe a case of a 36-year-old Asian man
      who presented following a recent trip to Delhi, India. He described fever, neck
      swelling, and arthralgia. Given his travel history an infectious cause for his
      presentation was presumed but multiple investigations were negative. Persistence
      of his symptoms led to lymph node biopsy to investigate for malignancy;
      surprisingly this revealed a necrotizing lymphadenitis in keeping with KFD. The
      patient made a full recovery with supportive treatment only. Conclusion. This
      case presented an opportunity to reflect on two common presenting complaints
      fever in the returning traveller and unexplained lymphadenopathy. Both
      presentations have a wide range of aetiologies to consider. Although KFD is rare,
      it is an important diagnosis to make as it can prevent further expensive and
      invasive investigations, as well as potentially harmful treatments and
      psychological stress to the patient. 

PMID- 25574175
TI  - A kikuchi-fujimoto disease case mimicking T cell lymphoma with prolonged Fever.
AB  - Kikuchi-Fujimoto disease (KFD) is a self-limited disease characterized by
      necrotizing lymphadenitis. Although cervical lymphadenitis in young women is the
      most familiar clinical presentation, it may take place in the etiology of fever
      in cases presenting with fever of unknown origin. A 33-year-old male case
      admitted with fever, nausea, vomiting, weight loss, and leukopenia for one month,
      subsequently developing axillary lymphadenopathy during followup, diagnosed as
      KFD with typical histopathological findings, and showing full recovery after the
      excision of lymph node was presented in this report. 

PMID- 25574177
TI  - Molecular mechanism of yisui shengxue granule, a complex chinese medicine, on
      thalassemia patients suffering from hemolysis and anemia of erythrocytes.
AB  - The objective of this study was to investigate the therapeutic biological
      mechanism of Yisui Shengxue Granule (YSSXG), a complex Chinese medicine, on the
      hemolysis and anemia of erythrocytes from patient with thalassemia disease.
      Sixteen patients with thalassemia (8 cases of alpha-thalassemia and 8 cases of
      beta-thalassemia) disease were collected and treated with YSSXG for 3 months. The
      improvements of blood parameter demonstrated that YSSXG had a positive clinical
      effect on patients with thalassemia disease. For patients with alpha-thalassemia
      disease, RT-PCR showed that YSSXG upregulated the relative mRNA expression level
      of alpha-globin to beta-globin and downregulated DNMT1, DNMT3a, and DNMT3b mRNA
      compared with pretreatment. Western blotting showed that YSSXG downregulated the
      expression of DNMT1 and DNMT3a. For patients with beta-thalassemia disease, the
      relative expression level of (A) gamma-globin to alpha-globin had an increasing
      trend and the level of BCL11A mRNA expression obviously increased. For all
      patients, RT-PCR showed that YSSXG upregulated mRNA expression of SPTA1 and SPTB.
      Activities of SOD and GSH-Px significantly increased and MDA obviously reduced on
      erythrocyte and blood serum after YSSXG treatment. TEM showed that YSSXG
      decreased the content of inclusion bodies. Activities of Na(+)K(+)-ATPtase and T
      ATPtase of erythrocyte increased significantly after YSSXG treatment. This study
      provides the basis for mechanisms of YSSXG on thalassemia suffering with
      hemolysis and anemia of erythrocytes from patient. 

PMID- 25574178
TI  - Safety and Tolerability of Essential Oil from Cinnamomum zeylanicum Blume Leaves
      with Action on Oral Candidosis and Its Effect on the Physical Properties of the
      Acrylic Resin.
AB  - The anti-Candida activity of essential oil from Cinnamomum zeylanicum Blume, as
      well as its effect on the roughness and hardness of the acrylic resin used in
      dental prostheses, was assessed. The safety and tolerability of the test product
      were assessed through a phase I clinical trial involving users of removable
      dentures. Minimum inhibitory concentration (MIC) and minimum fungicidal
      concentrations (MFC) were determined against twelve Candida strains. Acrylic
      resin specimens were exposed to artificial saliva (GI), C. zeylanicum (GII), and
      nystatin (GIII) for 15 days. Data were submitted to ANOVA and Tukey posttest
      (alpha = 5%). For the phase I clinical trial, 15 healthy patients used solution
      of C. zeylanicum at MIC (15 days, 3 times a day) and were submitted to clinical
      and mycological examinations. C. zeylanicum showed anti-Candida activity, with
      MIC = 625.0 ug/mL being equivalent to MFC. Nystatin caused greater increase in
      roughness and decreased the hardness of the material (P < 0.0001), with no
      significant differences between GI and GII. As regards the clinical trial, no
      adverse clinical signs were observed after intervention. The substance tested had
      a satisfactory level of safety and tolerability, supporting new advances
      involving the clinical use of essential oil from C. zeylanicum. 

PMID- 25574179
TI  - Data Mining of Acupoint Characteristics from the Classical Medical Text:
      DongUiBoGam of Korean Medicine.
AB  - Throughout the history of East Asian medicine, different kinds of acupuncture
      treatment experiences have been accumulated in classical medical texts.
      Reexamining knowledge from classical medical texts is expected to provide
      meaningful information that could be utilized in current medical practices. In
      this study, we used data mining methods to analyze the association between
      acupoints and patterns of disorder with the classical medical book DongUiBoGam of
      Korean medicine. Using the term frequency-inverse document frequency (tf-idf)
      method, we quantified the significance of acupoints to its targeting patterns
      and, conversely, the significance of patterns to acupoints. Through these
      processes, we extracted characteristics of each acupoint based on its treating
      patterns. We also drew practical information for selecting acupoints on certain
      patterns according to their association. Data analysis on DongUiBoGam's
      acupuncture treatment gave us an insight into the main idea of DongUiBoGam. We
      strongly believe that our approach can provide a novel understanding of unknown
      characteristics of acupoint and pattern identification from the classical medical
      text using data mining methods. 

PMID- 25574180
TI  - Use of auricular acupressure to improve the quality of life in diabetic patients
      with chronic kidney diseases: a prospective randomized controlled trial.
AB  - Background. Diabetic patients with chronic kidney disease (CKD) suffer from low
      quality of life (QOL). We aim to assess the effectiveness of auricular
      acupressure for QOL improvement in these patients. Materials and Methods. Sixty
      two participants were randomly assigned to an auricular or a control arm in a
      randomized controlled trial. Participants in the auricular arm were instructed to
      perform auricular acupressure 3-5 times per day for 3 months, when they were
      receiving conventional treatments. Participants in the control arm received
      conventional treatments only. The primary outcome was the summarized score of
      Kidney Disease and Quality of Life Short-Form (KDQOL-SF) at 3 months after
      randomization. The secondary outcomes included the 36-Item Short Form Health
      Survey (SF-36), glycosylated hemoglobin (HbA1c), and estimated glomerular
      filtration rate (eGFR). Results. The summarized KDQOL differed significantly
      between the acupressure (76.6, 95% CI, 72.2 to 81.0) and the control group (61.8,
      95% CI, 57.7 to 65.9). Similar results were found in the SF-36 scores. HbA1c and
      eGFR were not found to be significantly different between the arms and neither
      were the adverse events. Conclusion. Auricular acupressure was well tolerated in
      diabetic patients with chronic kidney diseases receiving hemodialysis. Future
      research is needed to confirm these results. 

PMID- 25574181
TI  - Interobserver reliability of four diagnostic methods using traditional korean
      medicine for stroke patients.
AB  - Objective. The aim of this study is to evaluate the consistency of pattern
      identification (PI), a set of diagnostic indicators used by traditional Korean
      medicine (TKM) clinicians. Methods. A total of 168 stroke patients who were
      admitted into oriental medical university hospitals from June 2012 through
      January 2013 were included in the study. Using the PI indicators, each patient
      was independently diagnosed by two experts from the same department.
      Interobserver consistency was assessed by simple percentage agreement as well as
      by kappa and AC1 statistics. Results. Interobserver agreement on the PI
      indicators (for all patients) was generally high: pulse diagnosis signs (AC1 =
      0.66-0.89); inspection signs (AC1 = 0.66-0.95); listening/smelling signs (AC1 =
      0.67-0.88); and inquiry signs (AC1 = 0.62-0.94). Conclusion. In four
      examinations, there was moderate agreement between the clinicians on the PI
      indicators. To improve clinician consistency (e.g., in the diagnostic criteria
      used), it is necessary to analyze the reasons for inconsistency and to improve
      clinician training. 

PMID- 25574182
TI  - Cytotoxic Activities against Breast Cancer Cells of Local Justicia gendarussa
      Crude Extracts.
AB  - Justicia gendarussa methanolic leaf extracts from five different locations in the
      Southern region of Peninsular Malaysia and two flavonoids, kaempferol and
      naringenin, were tested for cytotoxic activity. Kaempferol and naringenin were
      two flavonoids detected in leaf extracts using gas chromatography-flame
      ionization detection (GC-FID). The results indicated that highest concentrations
      of kaempferol and naringenin were detected in leaves extracted from Mersing with
      1591.80 mg/kg and 444.35 mg/kg, respectively. Positive correlations were observed
      between kaempferol and naringenin concentrations in all leaf extracts analysed
      with the Pearson method. The effects of kaempferol and naringenin from leaf
      extracts were examined on breast cancer cell lines (MDA-MB-231 and MDA-MB-468)
      using MTT assay. Leaf extract from Mersing showed high cytotoxicity against MDA
      MB-468 and MDA-MB-231 with IC50 values of 23 MUg/mL and 40 MUg/mL, respectively,
      compared to other leaf extracts. Kaempferol possessed high cytotoxicity against
      MDA-MB-468 and MDA-MB-231 with IC50 values of 23 MUg/mL and 34 MUg/mL,
      respectively. These findings suggest that the presence of kaempferol in Mersing
      leaf extract contributed to high cytotoxicity of both MDA-MB-231 and MDA-MB-468
      cancer cell lines. 

PMID- 25574183
TI  - Antioxidant and antiadipogenic activities of galkeun-tang, a traditional korean
      herbal formula.
AB  - Galkeun-tang (GKT; Galgen-tang in Chinese and Kakkon-to in Japanese), a
      traditional herbal formula, has been used for treatment of the common cold. Here,
      we report in vitro antioxidant and antiadipogenic effects of GKT. GKT increased
      the activities of scavenging 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic
      acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. GKT also
      significantly reduced the malondialdehyde (MDA) generation during low-density
      lipoprotein (LDL) oxidation and the electrophoretic mobility of oxidized LDL,
      indicating inhibitory effects of GKT on Cu(2+)-mediated oxidation of LDL.
      Regarding antiadipogenic activity, GKT treatment significantly suppressed lipid
      accumulation, triglyceride production, and glycerol-3-phosphate dehydrogenase
      (GPDH) activity in differentiated 3T3-L1 adipocytes. Consistent with this, GKT
      significantly reduced the secretion of leptin, a major adipokine, in
      differentiated 3T3-L1 adipocytes. Overall, our findings suggest that GKT has the
      potential for antioxidative and antiadipogenic properties. 

PMID- 25574176
TI  - The shared pathoetiological effects of particulate air pollution and the social
      environment on fetal-placental development.
AB  - Exposure to particulate air pollution and socioeconomic risk factors are shown to
      be independently associated with adverse pregnancy outcomes; however, their
      confounding relationship is an epidemiological challenge that requires
      understanding of their shared etiologic pathways affecting fetal-placental
      development. The purpose of this paper is to explore the etiological mechanisms
      associated with exposure to particulate air pollution in contributing to adverse
      pregnancy outcomes and how these mechanisms intersect with those related to
      socioeconomic status. Here we review the role of oxidative stress, inflammation
      and endocrine modification in the pathoetiology of deficient deep placentation
      and detail how the physical and social environments can act alone and
      collectively to mediate the established pathology linked to a spectrum of adverse
      pregnancy outcomes. We review the experimental and epidemiological literature
      showing that diet/nutrition, smoking, and psychosocial stress share similar
      pathways with that of particulate air pollution exposure to potentially
      exasperate the negative effects of either insult alone. Therefore, socially
      patterned risk factors often treated as nuisance parameters should be explored as
      potential effect modifiers that may operate at multiple levels of social
      geography. The degree to which deleterious exposures can be ameliorated or
      exacerbated via community-level social and environmental characteristics needs
      further exploration. 

PMID- 25574184
TI  - Trend and pattern of herb and supplement use in the United States: results from
      the 2002, 2007, and 2012 national health interview surveys.
AB  - Background. In 1990s, complementary and alternative medicine (CAM), including use
      of herbs and supplements, gained popularity in the United States. However, more
      recent surveys suggest that demand for herbs and supplements has stabilized.
      Objective. This study examined the prevalence, patterns, and changes in herb and
      supplement use among the US adults, using the 2002, 2007, and 2012 National
      Health Interview Surveys (NHIS). Methods. Weighted population estimates were
      derived from three complementary and alternative medicine supplements to the
      NHIS. Prevalence rates for herb and supplement use were compared, using Wald chi
      square tests to measure changes between years. Results. An estimated 40.6 million
      US adults reported herb and supplement use in 2012. However, the rate of herb and
      supplement use dropped from 18.9% in 2002 to 17.9% in 2007 and 2012 (P < 0.05).
      This decline in use was more pronounced among women, racial or ethnic minorities,
      and adults with low incomes. Conclusion. Herb and supplements use remains common
      in the USA, but adult use rates are on the decline. It is still important for
      health care providers to ask patients about herb and supplement use. 

PMID- 25574185
TI  - Feature selection in classification of eye movements using electrooculography for
      activity recognition.
AB  - Activity recognition is needed in different requisition, for example,
      reconnaissance system, patient monitoring, and human-computer interfaces. Feature
      selection plays an important role in activity recognition, data mining, and
      machine learning. In selecting subset of features, an efficient evolutionary
      algorithm Differential Evolution (DE), a very efficient optimizer, is used for
      finding informative features from eye movements using electrooculography (EOG).
      Many researchers use EOG signals in human-computer interactions with various
      computational intelligence methods to analyze eye movements. The proposed system
      involves analysis of EOG signals using clearness based features, minimum
      redundancy maximum relevance features, and Differential Evolution based features.
      This work concentrates more on the feature selection algorithm based on DE in
      order to improve the classification for faultless activity recognition. 

PMID- 25574186
TI  - Eco-certification and greening the Brazilian soy and corn supply chains.
AB  - Garrett et al's recent letter (2013 Environ. Res. Lett.8 044055) shows the trade
      value of Brazil's production of non-genetically modified (GM) crops, and argues
      that production for this niche market laid the foundation for the expansion of a
      variety of non-GM and eco-certification systems. We argue that the conditions
      underlying the development and perpetuation of the non-GM certification systems
      are transient. The expansion of soy production has dampened the conditions that
      promoted the dominance of non-GM soy in the region. The state at the heart of the
      production of conventional soy, Mato Grosso, already has transitioned to almost
      90% GM soy in the most recent agricultural season. The continued viability of eco
      certification systems depends on strengthening institutions on the demand side,
      and ensuring farm-level costs on the supply side match price premiums reaching
      the farm level.

PMID- 25574188
TI  - Multiple drug resistance due to resistance to stem cells and stem cell treatment
      progress in cancer (Review).
AB  - In recent years, the cancer stem cell (CSC) theory has provided a new angle in
      the research of cancer, and has gradually gained significance. According to this
      theory, the multiple drug resistance (MDR) of cancer is most likely due to the
      resistance of CSCs, and a significant quantity of research has been carried out
      into the MDR mechanisms of CSC. Over time, some of these mechanisms have been
      gradually accepted, including ATP-binding cassette transporters, aldehyde
      dehydrogenase, the CSC microenvironment and epithelial to mesenchymal transition.
      In the present review, we summarize these mechanisms in detail and review
      possible appropriate therapy plans against CSCs based on CSC theory.

PMID- 25574187
TI  - Therapeutic potential of hepatocyte growth factor against cerebral ischemia
      (Review).
AB  - The effective treatment for cerebral ischemia has not yet been established.
      Hepatocyte growth factor (HGF) is a potent pleiotropic cytokine that is involved
      in cell and tissue regeneration, including in the central nervous system. Studies
      have demonstrated that an exogenous administration of HGF protects brain tissue
      from ischemic damage. In response to binding to the receptor c-Met, HGF activates
      the downstream signaling pathways (including the phosphatidylinositol 3
      kinase/Akt, Ras/MAPK and signal transducer and activator of transcription
      pathways) which leads to various cellular responses involved in angiogenesis,
      glial scar formation, anti-apoptosis and neurogenesis. The purpose of this review
      is to summarize the present understanding of the therapeutic potential of HGF in
      cerebral ischemia.

PMID- 25574189
TI  - Effects of a nutrient mixture on immunohistochemical localization of cancer
      markers in human cervical cancer HeLa cell tumor xenografts in female nude mice.
AB  - Although fully treatable in the early stages, once cervical cancer has
      metastasized, patient outcome is poor. The main objective of this study was to
      examine the effect of dietary supplementation with a nutrient mixture (NM)
      containing lysine, ascorbic acid, proline, green tea extract and other
      micronutrients on HeLa cell xenografts in nude female mice. Tumor growth was
      measured and immunohistochemical staining was evaluated for the following cancer
      markers: Ki67 (proliferation); matrix metalloproteinase (MMP)-2 and -9
      (invasion/metastasis); vascular endothelial growth factor (VEGF) (angiogenesis);
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and B-cell
      lymphoma 2 (Bcl-2) (apoptosis); cyclooxygenase 2 (COX-2) and inducible nitric
      oxide synthase (iNOS) (inflammation); and glutathione S-transferase pi (GSTpi) (a
      general cancer marker). Following housing for a week, 5/6-week-old female athymic
      nude mice (n=12) were inoculated subcutaneously with 3*106 HeLa cells in 0.2 ml
      phosphate-buffered saline and 0.1 ml MatrigelTM and randomly divided into two
      groups; control group mice were fed regular mouse chow and NM group mice the
      regular diet supplemented with 0.5% NM (w/w). After four weeks, the mice were
      sacrificed and their tumors were excised and processed for histology. The NM
      strongly inhibited the growth of HeLa xenografts in nude mice. The mean tumor
      weight was reduced to 59% (P=0.001) in the mice fed the NM compared with the
      tumor weight in the controlled diet mice. Ki67, MMP-2 and -9, VEGF, TUNEL, Bcl-2,
      COX-2, iNOS and GSTpi all showed a lower intensity and frequency of staining in
      the NM group compared with that in the control group. In conclusion, NM
      supplementation strongly inhibited tumor growth and cancer markers in female nude
      mice injected with HeLa xenografts.

PMID- 25574190
TI  - Portulaca oleracea L. aids calcipotriol in reversing keratinocyte differentiation
      and skin barrier dysfunction in psoriasis through inhibition of the nuclear
      factor kappaB signaling pathway.
AB  - Psoriasis affects 2-4% of the population worldwide and its treatment is currently
      far from satisfactory. Calcipotriol and Portulaca oleracea have been reported to
      exhibit the capacity to inhibit inflammation in psoriatic patients and improve
      their clinical condition. However, the efficacy of a combination regimen of these
      two components remains unknown. The aim of the present study was to explore the
      therapeutic efficacy of P. oleracea extract combined with calcipotriol on plaque
      psoriasis and its potential mechanism. Eleven patients with plaque psoriasis were
      treated with humectant containing the active ingredients of P. oleracea extract,
      with or without 0.005% calcipotriol ointment in a right-left bilateral lesion
      self-control study. Differences were evaluated by investigation of the clinical
      efficacy, adverse effects, skin barrier function, histological structure,
      expression and proliferation of keratinocytes, differentiation markers
      (cytokeratin 10, filaggrin and loricrin), inflammatory factors [tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-8], as well as the status of the nuclear
      factor kappaB (NF-kappaB) pathway. The combination of P. oleracea and
      calcipotriol was revealed to decrease adverse effects, reduce transepidermal
      water loss, potently reverse keratinocyte differentiation dysfunction, and
      inhibit the expression of TNF-alpha and IL-8 and the phosphorylation of the NF
      kappaB inhibitor IkappaBalpha. This treatment is therefore anticipated to be
      suitable for use as a novel adjuvant therapy for psoriatic patients.

PMID- 25574191
TI  - Immunohistochemical demonstration of alteration of beta-catenin during tumor
      metastasis by different mechanisms according to histology in lung cancer.
AB  - The protein beta-catenin exhibits a dual function in cells, by acting as a major
      structural component of cell-cell adherens junctions and as a central signaling
      molecule in the Wnt signaling pathway. However, how the regulation of beta
      catenin expression during tumor metastasis in non-small cell lung cancer (NSCLC)
      varies according to histological type remains unclear. To investigate the
      regulatory mechanism of beta-catenin on tumor metastasis, the present study
      compared the expression of Wnt1, beta-catenin and E-cadherin in 41 primary NSCLC
      tumors and their corresponding metastatic lesions by immunohistochemistry.
      Altered expression of beta-catenin was more frequent in the metastatic tumors
      (34/41, 82.9%) than in the corresponding primary tumors (24/41, 58.5%; P<0.05).
      There were 12 cases [nine of adenocarcinoma (ADC) and three of squamous cell
      carcinoma (SqCC)] that revealed discordant beta-catenin expression between the
      primary tumors and the corresponding metastatic lesions. Of these, 11 cases
      (11/12, 91.7%; nine ADCs and two SqCCs) demonstrated acquired beta-catenin
      alterations in the metastatic lesions. Subgroup analysis of these nine ADCs
      revealed that six cases (6/9, 66.7%) were accompanied by E-cadherin loss but no
      Wnt1 overexpression. Subgroup analysis of the three SqCCs revealed discordant
      beta-catenin expression. Two cases (2/3, 66.7%) demonstrated acquired beta
      catenin expression during metastatic progression with Wnt1 overexpression but no
      change in E-cadherin expression. One case of SqCC revealed normal beta-catenin
      expression in the metastasis although the expression was aberrant in the primary
      tumor. The results of the present study revealed that the changes in beta-catenin
      expression occurred during tumor metastasis by different mechanisms, depending on
      histological type. The alterations in beta-catenin expression may be regulated by
      a cadherin-catenin system in ADCs with reduced membranous expression of E
      cadherin, but mediated by Wnt1 overexpression in SqCCs with cytoplasmic or
      nuclear transition types.

PMID- 25574192
TI  - Endoplasmic reticulum stress response in spontaneously hypertensive rats is
      affected by myocardial ischemia reperfusion injury.
AB  - Cell apoptosis induced by endoplasmic reticulum (ER) stress appears to be one of
      the main causes of myocardial necrosis following myocardial ischemia/reperfusion
      (MI/R). The C/EBP homologous protein (CHOP) pathway is the main pathway through
      which apoptosis is induced during ER stress. Glucose-regulated protein 78 (GRP78)
      is an important protein involved in the CHOP pathway. The present study
      investigated the hypothesis that MI/R activates the CHOP pathway through
      signaling via a pathway involving PKR-like ER kinase (PERK), alpha-subunit of
      eukaryotic initiation factor 2 (eIF2alpha) and activating transcription factor 2
      (ATF2). Immunohistochemical staining of the heart tissues from spontaneously
      hypersensitive rats indicated that MI/R injury increases CHOP and GPR78 protein
      expression levels. To further analyze the mechanism by which MI/R injury induces
      apoptosis by ER stress, the expression levels of five marker proteins involved in
      the hypothetical PERK-eIF2alpha-ATF2 pathway were detected, namely PERK,
      phosphorylated PERK (P-PERK), eIF2alpha, phosphorylated eIF2alpha (P-eIF2alpha)
      and ATF2. An increase in the collective expression levels of these proteins would
      indicate that apoptosis was induced by this signaling pathway. In addition, the
      study also explored whether hypertension affects the signaling pathway of MI/R
      induced myocardial apoptosis by treating spontaneously hypertensive rats (SHRs)
      with captopril (an effective drug used to treat hypertension). Rats treated with
      captopril experienced a reduction in blood pressure to normal levels, but no
      marked differences in the expression levels of the tested proteins or in MI/R
      injury severity compared with those in untreated rats. These results suggest that
      MI/R activates the CHOP pathway during ER stress by activating the PERK-eIF2alpha
      ATF2 pathway and that hypertension does not affect this signaling pathway.

PMID- 25574194
TI  - Two cases of paraneoplastic limbic encephalitis associated with small cell lung
      cancer and a literature review.
AB  - In the present study, two cases of paraneoplastic limbic encephalitis (PLE)
      associated with small cell lung cancer were reported. Using avidin-biotin
      immunoperoxidase methods, purified recombinant HuD western blotting and Euroline
      Neuronal Antigens Profile 2 immunoglobulin G western blotting, it was found that
      the well-characterized anti-Hu and anti-amphiphysin onconeuronal antibodies were
      present in the serum/cerebrospinal fluid of the patients. With a review of the
      literature, it was found that patients with PLE of Chinese Han nationality had
      two types of clinical manifestations, simple and complex, and that the lesions
      could also be divided into focal and scalable lesions. Furthermore, the clinical
      manifestations and lesion scopes were associated with certain types of cancer and
      antibodies. In addition, it was found that the prognosis for patients with PLE
      with autoantibodies targeting membrane antigens is improved compared with that
      for patients with PLE with autoantibodies targeting intracellular antigens, due
      to an increased sensitivity to immunomodulatory treatments and anti-cancer
      therapy.

PMID- 25574193
TI  - Antitumor effects of a dual cancer-specific oncolytic adenovirus on colorectal
      cancer in vitro and in vivo.
AB  - The efficacy and specificity of treatment are major challenges for cancer gene
      therapy. Oncolytic virotherapy is an attractive drug delivery platform for cancer
      gene therapy. In the present study, the dual-specific antitumor oncolytic
      adenovirus, Ad-Apoptin-hTERT-E1a, was used to infect SW1116 human colorectal
      carcinoma (CRC) cell lines and CT26 mouse-CRC-cell bearing BALB/c mouse models
      for testing antitumor effects in vitro and in vivo. The in vitro assays revealed
      that infection with Ad-Apoptin-hTERT-E1a induced a significant cytotoxic effect
      on the CRC cell line, SW1116; however, the normal human cell line, GES, was only
      slightly inhibited by the recombinant adenovirus. Acridine orange and ethidium
      bromide staining and an annexin V assay indicated that infection of SW1116 cells
      with Ad-Apoptin-hTERT-E1a resulted in a significant induction of apoptosis.
      Furthermore, western blotting and flow cytometry revealed a decrease in the
      mitochondrial membrane potential (MMP), the release of cytochrome c and the
      activation of caspase 3, 6 and 7 in Ad-Apoptin-hTERT-E1a-infected SW1116 cells.
      In the animal models, Ad-Apoptin-hTERT-E1a was shown to significantly inhibit
      tumor growth and extend the survival times of the animals. Therefore, the
      experimental results indicated that Ad-Apoptin-hTERT-E1a has potential for
      application in tumor gene therapy.

PMID- 25574195
TI  - Reduction of facial pigmentation of melasma by topical lignin peroxidase: A novel
      fast-acting skin-lightening agent.
AB  - The aim of the present study was to evaluate the efficacy and safety of lignin
      peroxidase (LIP) as a skin-lightening agent in patients with melasma. A self
      controlled clinical study was performed in 31 women who had melasma on both sides
      of the face. This study involved 8 weeks of a full-face product treatment. The
      skin color was measured at days 0, 7, 28 and 56 using a chromameter on the
      forehead and cheeks. Standardized digital photographic images of each side of the
      face of all subjects were captured by a complexion analysis system. Clinical
      scores of the pigmentation were determined by two dermatologists. After using the
      LIP whitening lotion for 7 days, the luminance (L*) values of the melasma and the
      normal skin were significantly increased from baseline. The L* values continued
      to increase at days 28 and 56. The melasma area severity index (MASI) score was
      statistically decreased after 28 days of treatment. No treatment-related adverse
      events were observed. LIP whitening lotion was able to eliminate the skin
      pigmentation after 7 days of treatment, and provides a completely innovative
      approach to rapid skin lightening. The LIP whitening lotion exhibited good
      compatibility and was well tolerated.

PMID- 25574196
TI  - Genomic alterations on 8p21-p23 are the most frequent genetic events in stage I
      squamous cell carcinoma of the lung.
AB  - Genetic alterations in the early stages of cancer have a close correlation with
      tumor initiation and potentially activate downstream pathways implicated in tumor
      progression; however, the method of initiation in sporadic neoplasias is largely
      unknown. In this study, whole-genome microarray-comparative genomic hybridization
      was performed to identify the early genetic alterations that define the prognosis
      of patients with stage I squamous cell carcinoma (SCC) of the lung. The most
      striking finding was the high frequency of copy number losses and hemizygous
      deletions on chromosome 8p, which occurred in 94.7% (18/19) and 63.2% (12/19) of
      the cases, respectively, with a delineated minimal common region of 8p21.1-p23.3.
      More specifically, three loci of homozygous deletions at 8p23.1 were noted in
      21.1% (4/19) of the cases. This region contains the following possible target
      genes, which have previously not been implicated to play a pathogenic role in
      stage I SCCs: MSRA, MFHAS1, CLDN23, DEFB106A, DEFB105A, LOC441316, FAM90A7P and
      LOC441318. These findings indicate that genetic alterations on chromosome 8p may
      be the first step in the initiation of genomic instability in early SCCs, and the
      newly identified genes in the 8p23.1 chromosomal region might be of interest for
      the study of the pathophysiology of stage I SCC, as potential targets for
      therapeutic measures.

PMID- 25574197
TI  - Treatment with retinoic acid and lens epithelial cell-conditioned medium in vitro
      directed the differentiation of pluripotent stem cells towards corneal
      endothelial cell-like cells.
AB  - Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have
      extensive self-renewal capacity and the potential to differentiate into all
      tissue-specific cell lineages, including corneal endothelial cells (CECs). They
      are a promising prospect for the future of regenerative medicine. The method of
      derivation of CECs from ESCs and iPSCs, however, remains to be elucidated. In
      this study, mouse ESCs and iPSCs were induced to differentiate into CECs using
      CEC embryonic development events as a guide. All-trans retinoic acid (RA)
      treatment during the embryoid body (EB) differentiation step was used to promote
      neural crest (NC) cell differentiation as first step and was followed by a second
      induction in CEC- or lens epithelial cell (LEC)-conditioned medium (CM) to
      ultimately generate CEC-like cells. During the corresponding differentiation
      stages, NC developmental markers and CEC differentiation markers were detected at
      the protein level using immunocytochemistry (ICC) and at the mRNA level by
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR). During
      the first stage, the data indicated that 4 days of treatment with 1 MUM RA
      starting on day 4 of EB formation favored NC cell differentiation and that
      plating on gelatin-coated plates led to cell migration out of the EBs. The second
      stage differentiation results showed that the CM, particularly the LEC-CM,
      enhanced the yield of polygonal cells with CEC-specific marker expression shown
      by ICC and RT-qPCR. This study demonstrates that mouse ESCs and iPSCs were
      induced and expressed CEC differentiation markers when subjected to a two-step
      inducement process, suggesting that they are a promising resource for corneal
      endothelium failure replacement therapy in the future.

PMID- 25574199
TI  - A new rat model of auxiliary partial heterotopic liver transplantation with liver
      dual arterial blood supply.
AB  - Auxiliary partial heterotopic liver transplantation (APHLT) with portal vein
      arterialization is a valuable procedure to be considered in the treatment of
      patients with acute liver failure and metabolic liver diseases. The aim of this
      study was to develop a new rat model of APHLT with liver dual arterial blood
      supply (LDABS). A total of 20 rats were used. The donor liver was resected, and
      the celiac trunk was reserved. Left and medial hepatic lobes accounting for 70%
      of the liver mass were removed en bloc and the suprahepatic caval vein was
      ligated simultaneously. Thus, 30% of the donor liver was obtained as the graft.
      Sleeve anastomosis of the graft portal vein and splenic artery were performed
      after narrowing the portal vein lumen through suturing. The right kidney of the
      recipient was removed, and sleeve anastomosis was performed between the celiac
      trunk of the graft and the right renal artery of the recipient. In addition, end
      to-end anastomosis was performed between the infrahepatic caval vein of the graft
      and the right renal vein of the recipient. Following the reperfusion of the
      graft, the blood flow of the arterialized portal vein was controlled within the
      physiological range through suturing and narrowing under monitoring with an
      ultrasonic flowmeter. The bile duct of the graft was implanted into the duodenum
      of the recipient through an internal stent catheter. A 70% section of the native
      liver (left and medial hepatic lobes) was resected using bloodless hepatectomy.
      The mean operative duration was 154.5+/-16.4 min, and the warm and cold ischemia
      times of the graft were 8.1+/-1.1 min and 64.5+/-6.6 min, respectively. The blood
      flow of the arterialized portal vein to the graft was 1.8+/-0.3 ml/min/g liver
      weight. The success rate of model establishment (waking with post-surgical
      survival of >24 h) was 70% (7/10). Following successful model establishment, all
      rats survived 7 days post-surgery (100%; 7/7). The graft was found to be soft in
      texture and bright red in color following exploratory laparotomy. In conclusion,
      a new rat model of APHLT with LDABS without stent for vascular reconstruction was
      developed. This is a feasible and reliable rat model for liver transplantation
      study.

PMID- 25574198
TI  - Different levels of glycosylated hemoglobin influence severity and long-term
      prognosis of coronary heart disease patients with stent implantation.
AB  - The aim of this study was to investigate the correlation between glycosylated
      hemoglobin (HbA1c) levels and the severity and long-term prognosis of coronary
      heart disease (CHD) with stent implantation. A total of 2,825 consecutive
      patients with stent implantation were stratified into three groups based on the
      levels of HbA1c: Low HbA1c group (group A, HbA1c <=5.9% or 41 mmol/mol; n=1,035),
      moderate HbA1c group (group B, 5.9%< HbA1c <6.8% or 41< HbAlc <51 mmol/mol;
      n=1,025) and high HbA1c group (group C, HbA1c >=6.8% or 51 mmol/mol; n=765). The
      impact of HbA1c on the Gensini score and the long-term prognosis of CHD with
      stent implantation were observed. After an average of 1 year of follow-up of the
      2,825 patients in a hospital cohort, participants with low or high HbA1c had a
      higher risk of major adverse cardiac events (MACE) and target lesion
      revascularization (TLR) compared with participants with moderate HbA1c after
      adjusting for multiple potential confounders (hazard ratios for low HbAlc, 1.505
      and 1.478, respectively, and for high HbAlc, 1.626 and 1.522, respectively).
      Analysis of HbA1c as a continuous variable showed that each 1% increase of HbA1c
      was significantly associated with decreased risks of MACE and TLR of 53.5 and
      54.2%, respectively, in those with a low HbA1c level and with increased risks of
      MACE and TLR of 9.5 and 9.2%, respectively, in those with a moderate or high
      HbA1c level, suggesting a U-shaped association between HbA1c and the risk of MACE
      and TLR. In conclusion, HbA1c levels, either as a continuous variable or a
      categorical variable, have a U-shaped correlation with MACE and TLR in CHD
      patients with stent implantation, even after adjustment for multiple confounders.

PMID- 25574200
TI  - In vivo imaging of adipose-derived mesenchymal stem cells in female nude mice
      after simulated childbirth injury.
AB  - The aim of the present study was to track in vivo the distribution and survival
      of adipose-derived mesenchymal stem cells (ASCs) transplanted into female BALB/c
      nude mice following simulated childbirth injury, using green fluorescent protein
      and luciferase dual labeling, bioluminescent imaging (BLI) and histological
      evaluation. The results demonstrated that the dually labeled ASCs could be
      detected for up to eight weeks in vivo. The number of implanted cells decreased
      during the first three weeks, and then stabilized until the end of the
      experiment. According to the linear regression plot, ~27,621 implanted cells
      survived until eight weeks after implantation. Transplanted ASCs predominantly
      existed at the inoculation site of the vagina, with little or no spread to other
      organs. Histological analysis confirmed the survival of the engrafted ASCs. The
      study provided basic evidence that BLI techniques can be used to monitor ASCs in
      vivo in real time and in the long term. Through local administration, ASCs could
      survive in the long term to facilitate repair following pelvic-floor injury.

PMID- 25574202
TI  - Preventive effect of pentoxifylline on contrast-induced acute kidney injury in
      hypercholesterolemic rats.
AB  - Oxidative stress is an important mechanism of contrast-induced acute kidney
      injury (CIAKI). The optimal strategy to prevent CIAKI remains unclear. The aim of
      the present study was to assess the effect of pentoxifylline, a nonspecific
      phosphodiesterase inhibitor, on the prevention of CIAKI. A total of 32 healthy
      male Sprague-Dawley rats were randomly divided into normal dietary group (NN;
      n=8) and a high cholesterol-supplemented dietary group (HN; 4% cholesterol and 1%
      cholic acid; n=24). At the end of eight weeks, the rats in the high cholesterol
      diet group were randomly divided into three subgroups (n=8 in each group). CIAKI
      was induced in two of the subgroups via intravenous injection of the
      radiocontrast media iohexol (10 ml/kg). Pentoxifylline (50 mg/kg) was
      administered to one of the iohexol-treated groups via intraperitoneal injection
      12 h prior to and following contrast media (CM) injection. Kidney function
      parameters and oxidative stress markers were then measured. The renal
      pathological changes were evaluated using hematoxylin and eosin staining and
      scored semi-quantitatively. In iohexol-injected rats, serum creatinine (Scr),
      renal pathological scores, renal malondialdehyde (MDA) content, renal NADPH
      oxidase activity, fractional excretion of sodium (FENa%) and fractional excretion
      of potassium (FEK%) were significantly increased (P<0.01). The Scr, histologic
      scores, renal MDA content, NADPH oxidase activity, FENa% and FEK% in the rats
      treated with pentoxifylline prior to iohexol were observed to be reduced compared
      with those in rats treated with iohexol alone (P<0.01). This suggests that
      pentoxifylline significantly attenuates renal injuries, including tubular
      necrosis and proteinaceous casts induced by CM. It may be concluded that
      pentoxifylline protected the renal tissue from the nephrotoxicity induced by low
      osmolar CM via an antioxidant effect.

PMID- 25574201
TI  - Curcumin protects against lipopolysaccharide-induced vasoconstriction dysfunction
      via inhibition of thrombospondin-1 and transforming growth factor-beta1.
AB  - Sepsis is a complex syndrome characterized by the development of progressive
      dysfunction in multiple organs. The aim of the present study was to investigate
      the protective effect of curcumin against lipopolysaccharide (LPS)-induced
      vasoconstrictive dysfunction, and to investigate the possible underlying
      mechanism. Male Sprague-Dawley rats were randomly divided into the following
      groups: Control, sepsis and curcumin. A sepsis model was established by an
      intraperitoneal (i.p.) injection of 5 mg/kg LPS. Thoracic aortic rings obtained
      from the rats were mounted in an organ bath and the vasoconstriction of the rings
      was recorded. In addition, the serum E-selectin levels were determined by an
      enzyme-linked immunosorbent assay. The expression levels of thrombospondin (TSP)
      1 and transforming growth factor (TGF)-beta1 in the aortic tissue were detected
      by immunohistochemistry. Vasoconstriction of the aortic rings was found to
      significantly decrease in the sepsis rats when compared with the control group.
      However, curcumin (10 or 20 mg/kg, i.p.) prevented the vasoconstrictive
      dysfunction induced by LPS. The serum level of E-selectin and the expression
      levels of TSP-1 and TGF-beta1 significantly increased in the sepsis rats when
      compared with the control group rats; however, the levels decreased significantly
      following treatment with curcumin (10 or 20 mg/kg). Furthermore, hematoxylin and
      eosin staining revealed that curcumin alleviated the LPS-induced damage in the
      aortic tunica intima and tunica media. Therefore, the results indicated that
      curcumin alleviates LPS-induced vasoconstrictive dysfunction in the thoracic
      aorta of rats. In addition, the inhibition of TSP-1 and TGF-beta1 expression may
      be involved in the mechanism underlying this protective effect.

PMID- 25574203
TI  - Association between VEGFR-3 expression and lymph node metastasis in non-small
      cell lung cancer.
AB  - Vascular endothelial growth factor receptor (VEGFR)-3 is considered to be
      associated with lymphangiogenesis. The aim of the present study was to identify
      the clinical significance of VEGFR-3 expression and lymph node metastasis in
      patients with non-small-cell lung cancer (NSCLC). Lung tumor tissue samples and
      196 lymph nodes from 52 patients with NSCLC were analyzed. In addition, lung
      tissue samples and 8 lymph nodes from 10 patients with lung diseases other than
      cancer were included as controls. Semiquantitative multiplex reverse
      transcription technology was applied to measure the mRNA expression levels of
      VEGFR-3, while VEGFR-3 protein expression levels were assessed
      immunohistochemically. The total number of lymphatic vessels was counted and the
      microlymphatic vessel density (MLVD) was calculated. The results indicated that
      the VEGFR-3 mRNA expression level in lymph node tissue from the group with lymph
      node metastasis was significantly lower compared with the group without lymph
      node metastasis (0.281+/-0.166 vs. 0.158+/-0.158; t=4.849; P<0.001). The VEGFR-3
      mRNA expression levels in the lung tumor tissue of the NSCLC patients exhibited
      no statistically significant difference between the lymph node metastasis and
      lymph node non-metastasis groups (0.139+/-0.137 vs. 0.142+/-0.123; t=0.08;
      P>0.05). In addition, in the lymph node metastasis group, there was no
      statistically significant difference between the metastasis-positive and 
      negative lymph nodes (0.158+/-0.158 vs. 0.123+/-0.115; t=0.993; P>0.05) with
      regard to VEGFR-3 mRNA expression. Morphologically, VEGFR-3 immunoreactivity was
      primarily localized in the cytoplasm of the lymphatic endothelial cells, as well
      as a number of the cancer cells. MLVD was much higher in the lung tissue
      surrounding the tumor than in the tumor tissue, and was significantly higher in
      the lymph node metastasis group than in the lymph node non-metastasis group.
      VEGFR-3 expression levels were shown to correlate with lymph node metastasis in
      NSCLC patients, thus, may be a useful biomarker for lymph node metastasis
      prediction in NSCLC. MLVD is a key indictor of lymphatic vessel metastasis in
      NSCLC. An enhanced MLVD indicates lymphangiogenesis and lymphatic node
      metastasis, and may be an important predictor for tumor monitoring and prognosis.

PMID- 25574204
TI  - Totally laparoscopic gallbladder-preserving surgery: A minimally invasive and
      favorable approach for cholelithiasis.
AB  - The aim of the present study was to investigate the effectiveness of laparoscopic
      gallbladder-preserving surgery (L-GPS) for cholelithiasis and the feasibility and
      value of totally laparoscopic GPS (TL-GPS). A total of 517 patients underwent L
      GPS, including 365 cases of laparoscopy-assisted GPS (LA-GPS), 143 cases of TL
      GPS (preservation rate, 98.3%) and nine conversions to laparoscopic
      cholecystectomy. The surgeries were all performed by one medical team and the
      mean operating time was 72 min. All macroscopic calculi were removed through
      endoscopy. The number of calculi observed in the patients was between one and
      several dozen; diameters ranged between 0.1 and 2.5 cm. Only three cases of
      incisional infection were noted in the LA-GPS group and long-term follow-up
      showed a low recurrence rate of 1.2%. L-GPS is, therefore, an excellent approach
      to cure cholelithiasis and TL-GPS is a feasible and effective option that could
      avoid incisional complications.

PMID- 25574205
TI  - Computed tomography angiography manifestations of collateral circulations in Budd
      Chiari syndrome.
AB  - The aim of this study was to assess the computed tomography angiography (CTA)
      manifestations of collateral circulations in patients with Budd-Chiari syndrome
      (BCS). Eighty patients with BCS were examined by CT scan. Using the CTA images of
      the relevant blood vessels, including the affected hepatic veins (HVs) and
      inferior venae cavae (IVCs), the collateral circulations were reconstructed. In
      addition to obstructed HVs and IVCs, collateral circulations were found in each
      of the patients. The collateral circulations were classified as intrahepatic,
      extrahepatic and portosystemic pathways. Intrahepatic collateral pathways were
      further classified as the following six types: HV-accessory HV (n=51, 63.8%), HV
      HV (n=6, 7.5%), HV-accessory HV plus HV (n=6, 7.5%), IVC-HV/accessory HV-HV-right
      atrium (n=5, 6.3%), HV-umbilical vein (n=4, 5.0%) and HV-inferior phrenic vein
      (n=8, 10.0%). Extrahepatic collateral pathways included IVC-lumbar-ascending
      lumbar-hemiazygos/azygos vein (n=80, 100.0%), IVC-left renal-ascending lumbar
      hemiazygos vein (n=75, 93.8%), IVC-left renal-inferior phrenic vein (n=49,
      61.3%), IVC-renal -peri-renal -superficial epigastric vein (n=26, 32.5%) and
      superficial epigastric vein (n=12, 15.0%) types. The CTA characteristics of each
      type of collateral circulation were demonstrated. In conclusion, the present
      study revealed that CTA is able to show the intra- and extrahepatic collateral
      circulations of patients with BCS, which may be useful for therapeutic planning.

PMID- 25574206
TI  - Cardioprotective effect of epigallocatechin-3-gallate against myocardial
      infarction in hypercholesterolemic rats.
AB  - Cardiovascular diseases are closely associated with a high-cholesterol or high
      fat diet. The aim of the present study was to investigate the cadioprotective
      effect of epigallocatechin-3-gallate (EGCG) in high-fat diet-fed rats, with
      special emphasis on myocardial infarction. A high-fat diet was administered to
      male Wistar rats for 45 days and the rats of the treatment group were
      administered EGCG via intraperitoneal injection for the last 15 days. The serum
      lipid profile, antioxidant enzyme activity, lipid peroxidation, lipid metabolic
      proteins and cardiac tissue markers were assessed. The myocardium and aorta were
      also histopathologically examined. The high-fat diet-fed rats were found to be
      hypercholesterolemic or exhibited abnormal values in the selected parameters.
      However, these abnormalities were reversed to near-normal values in the rats
      administered EGCG. Similarly, the enzymatic antioxidant activity and non
      enzymatic antioxidant levels were improved with EGCG treatment in high-fat diet
      fed rats. In addition, EGCG activated sirtuin 1, endothelial nitric oxide
      synthase and AMP-activated protein kinase alpha, which suggests that its
      protective effect is mediated through the stimulation of lipid metabolism. The
      histopathological examination further revealed that EGCG significantly prevented
      the development of tissue abnormalities and improved the morphology of myocardial
      tissue. Taken together, our results suggested that EGCG plays a significant role
      in the protection of the cardiovascular system against the high-fat diet. This is
      a preliminary study, emphasizing on the cardioprotective properties of EGCG. We
      are currently analyzing the molecular mechanism underlying the protective effects
      of EGCG.

PMID- 25574207
TI  - Ulinastatin ameliorates acute kidney injury following liver transplantation in
      rats and humans.
AB  - Acute kidney injury (AKI) is a common complication following orthotopic liver
      transplantation (OLT) that evidently affects prognosis. However, no effective
      treatment exists for AKI. The aim of the present study was to elucidate whether
      ulinastatin application during OLT in humans can reduce kidney damage and improve
      renal function. In addition, the underlying mechanisms of ulinastatin were
      investigated on a rat autologous OLT (AOLT) model. In total, 60 patients
      undergoing an OLT were randomly selected to receive ulinastatin (U group; n=30)
      or saline (C group; n=30) during the OLT surgery. The patient demographics, AKI
      incidence rate, recovery indicators and renal injury indexes were measured during
      the perioperative period. In addition to the clinical trials, 40 rats were
      subjected to an AOLT and were divided into the control (C-R), sham-operation and
      ulinastatin treatment groups. Pathological renal damage, biomarkers of
      inflammation and oxidative stress were measured to investigate the effects and
      possible mechanisms of ulinastatin on AKI. In the clinical trials, ulinastatin
      application was shown to attenuate the incidence of AKI following OLT (P<0.05)
      and reduce the serum levels of cystatin C and urinary beta2 microglobulin within
      24 h of the OLT (P<0.05). Furthermore, ulinastatin was found to significantly
      improve the recovery of patients by reducing the time spent in the intensive care
      unit (P<0.01 vs. C group), the ventilation time and the hemodialysis rates
      (P<0.05 vs. C group). In the rat AOLT model, ulinastatin application was also
      shown to relieve renal pathological damage by reducing the serum cystatin C and
      creatinine levels. Notably, the levels of tumor necrosis factor-alpha,
      interleukin-6, hydrogen peroxide and reactive oxygen species were evidently
      reduced, while the level of superoxide dismutase was increased in the ulinastatin
      groups (P<0.05, vs. C-R group). In conclusion, ulinastatin application was
      demonstrated to protect against AKI following OLT by inhibiting inflammation and
      oxidation.

PMID- 25574208
TI  - Spinocerebellar ataxia type 3/Machado-Joseph disease manifested as spastic
      paraplegia: A clinical and genetic study.
AB  - The aim of the present study was to conduct a familial investigation and provide
      a genetic diagnosis to a family presenting with spastic paraplegia and clinically
      diagnosed with hereditary spastic paraplegia (HSP). Blood samples were obtained
      from the family, and mutations in the gene causing spinocerebellar ataxia type 3
      (SCA3)/Machado-Joseph disease (MJD), known as MJD1, were analyzed using the
      polymerase chain reaction, 8% denaturing polyacrylamide gel electrophoresis, and
      T-vector ligation and sequencing. The trinucleotide repeat number of the mutant
      allele was 80, leading to a genetic diagnosis of SCA3/MJD. This suggests that
      patients with SCA3/MJD characteristically present with typical spastic paraplegia
      without evident manifestations of ataxia. For those families with HSP involving
      the nervous system and showing genetic anticipation, an MJD1 genetic diagnosis
      should be considered to assist in clinical diagnosis of HSP.

PMID- 25574209
TI  - Risk factors for contralateral patent processus vaginalis determined by
      transinguinal laparoscopic examination.
AB  - Concurrent contralateral inguinal exploration in children with unilateral hernia
      or hydrocele is a subject of debate. The aim of the present study was to
      investigate the incidence of contralateral patent processus vaginalis (CPPV)
      using transinguinal laparoscopy (inguinoscopy). In addition, the risk factors of
      CPPV were evaluated in order to facilitate the selection of appropriate
      candidates for contralateral examination. A total of 119 patients who presented
      with unilateral hydrocele, inguinal hernia or cryptorchidism between 2001 and
      2008 underwent inguinoscopy during the ipsilateral surgery. All data were
      collected prospectively. The incidence of CPPV was investigated and the risk
      factors affecting the presence of CPPV were analyzed. Among these patients, 29
      individuals (24.4%) had CPPV confirmed by inguinoscopy. No surgical complications
      were observed during the inguinoscopy. Cases with suspicious ultrasound findings
      were at a higher risk of CPPV than cases with normal findings (odds ratio,
      13.800; P=0.004). A history of contralateral disease was also found to be a
      significant risk factor (odds ratio, 4.008; P=0.019). The present study
      identified that the significant risk factors for CPPV were suspicious findings on
      ultrasound examination and a history of contralateral disease. Therefore, it is
      concluded that performing inguinoscopy in children with these risk factors is
      beneficial.

PMID- 25574210
TI  - Metabolomic changes in patients with chronic obstructive pulmonary disease with
      abnormal Savda syndrome.
AB  - The aim of this study was to determine the metabolic biomarkers for abnormal
      Savda syndrome in patients with chronic obstructive pulmonary disease (COPD).
      Based on Traditional Uyghur Medicine (TUM) theory, a total of 103 patients with
      COPD were classified into abnormal Savda and non-abnormal Savda syndrome groups
      and 52 healthy volunteers acted as the control group. Blood samples from the
      three groups were analyzed using nuclear magnetic resonance (NMR) spectroscopy
      combined with orthogonal projection to latent structure-discriminant analysis.
      NMR tests showed that the regional distributions of the patients with COPD with
      abnormal Savda syndrome, those with non-abnormal Savda syndrome and the control
      group were completely separate (P>0.05). The patients with COPD with abnormal
      Savda syndrome exhibited relatively low levels of amino acids, glycoproteins and
      unsaturated lipids (P<0.05) but significantly higher levels of lactic acid,
      carnitine, acetone and acetoacetate (P<0.05) compared with the healthy controls.
      Abnormal Savda syndrome was one of the main types of syndrome among the patients
      with COPD; increased age, a longer duration of illness and a higher disease
      severity were characteristic of this type of syndrome. In addition, the present
      study provided biochemical evidence for the TUM theory-based classification of
      patients with COPD; these biomarkers can be used in the clinic for the diagnosis
      of COPD with abnormal Savda syndrome. The study also demonstrated that the plasma
      metabolic disorder in patients with COPD with abnormal Savda syndrome was more
      serious than that in the control and COPD with non-abnormal Savda syndrome
      groups. The plasma metabolic disorder was also associated with a low immune
      function of the body and endocrine and energy metabolism disorders.

PMID- 25574211
TI  - Myoclonic epilepsy with ragged-red fibers: A case report.
AB  - Myoclonic epilepsy with ragged-red fibers is a maternally inherited disease that
      is characterized by myoclonic epilepsy, cerebellar ataxia and progressive
      muscular weakness. The present study reports the case of a 25-year-old male who
      presented with paroxysmal left upper limb tics and weakness for two years.
      Neurological examination revealed intact cranial nerves, decreased deep tendon
      reflexes and decreased sensation of touch, pain and vibration. The gait of the
      patient was broad and he was unable to walk in a straight line. Local cortical
      atrophy was also observed in the left temporal-occipital cortex on a magnetic
      resonance imaging scan. The muscle biopsy revealed ragged-red fibers. Therefore,
      the present study hypothesized that imaging observations and follow-up
      examinations are important in patients with myoclonic epilepsy.

PMID- 25574213
TI  - Identification of a proliferator-activated receptor-gamma antagonist for the
      treatment of type 2 diabetes mellitus.
AB  - In the present study, a novel antagonist of the peroxisome proliferator-activated
      receptor-gamma (PPARgamma) was screened and identified, and a cell-based
      evaluation of the biological activity of this PPARgamma antagonist was conducted.
      The aim of the study was to produce results that may provide a foundation for the
      development of a novel compound in the treatment of type 2 diabetes mellitus.
      Since obesity is the main cause of insulin resistance and type 2 diabetes,
      identifying a new reagent that is able to inhibit adipocyte differentiation and
      lipid accumulation is a feasible method of developing novel anti-diabetes drugs.
      The PPARgamma antagonist was screened using a mammalian one-hybrid system and
      transcriptional activation. The effects of the compound on adipocyte
      differentiation were investigated by staining the preadipocytes with Oil Red O.
      In addition, the effects of the compound on the expression levels of genes
      associated with lipid metabolism were detected using quantitative polymerase
      chain reaction on differentiated mature 3T3-L1 adipocytes. As a PPARgamma
      antagonist, N-((1H-benzo[d]imidazol-2-yl)methyl) aniline (Compound Q) was shown
      to depress the transcriptional activity and coactivator recruitment of PPARgamma,
      as well as preadipocyte differentiation, in a concentration-dependent manner. The
      compound was also shown to decrease the expression levels of genes associated
      with PPARgamma-regulated lipid metabolism. In conclusion, the compound screening
      platform was demonstrated to be valid, and the present study identified a novel
      PPARgamma antagonist that was shown to effectively reduce the rate of adipocyte
      differentiation and the expression of genes associated with lipid metabolism.

PMID- 25574212
TI  - Protective effect of the combinations of glycyrrhizic, ferulic and cinnamic acid
      pretreatment on myocardial ischemia-reperfusion injury in rats.
AB  - The aim of this study was to find an effective drug cocktail pretreatment to
      protect myocardial tissue of the heart from ischemia-reperfusion (I/R) injury.
      The mechanisms underlying the effects of the drug cocktail were subsequently
      explored in order to expand the application of Dang-gui-si-ni-tang (DGSN), a
      Traditional Chinese Medicine. The active components of DGSN in the serum
      following oral administration were investigated using high-performance liquid
      chromatography. The activity of superoxide dismutase (SOD) and malondialdehyde
      (MDA) levels were then analyzed to show the effect of the active components in
      the treatment of myocardial I/R injury. An L16 (44) orthogonal experiment was
      utilized to determine the most effective cocktail mix and the mechanism
      underlying the effect of this mix on myocardial I/R injury was investigated. It
      was observed that FCG, a mixture of glycyrrhizic (50 mg/kg), cinnamic (200 mg/kg)
      and ferulic (300 mg/kg) acid, was the optimal drug cocktail present in DGSN. This
      was absorbed into the blood following oral administration and was shown to
      decrease MDA levels and increase the activity of SOD. In conclusion, the findings
      suggest that FCG, a combination of active ingredients in the DGSN decoction, can
      be absorbed into the blood and protect the myocardium from I/R injury.

PMID- 25574215
TI  - Histological observation of goblet cells following topical rebamipide treatment
      of the human ocular surface: A case report.
AB  - The topical administration of rebamipide (Mucosta(r)), an antiulcer agent,
      clinically increases the mucin level of tear film. The aim of this study was to
      report the histological changes of goblet cells following the topical
      administration of rebamipide to a patient with nevus of the lacrimal caruncle. A
      62-year-old male exhibited a pigmented nodule located in the lacrimal caruncle in
      the left eye. An excisional biopsy and subsequent surgical resection were
      conducted at the caruncle, prior to and three months after topical rebamipide
      administration. Histologically, a biopsy specimen revealed a pigmented nevus
      beneath the caruncle epithelium containing a few goblet cells [4 cells/high power
      field (HPF)]. A few nevus cells were present at the surgical margin. By contrast,
      the secondary resected specimen obtained three months after the initiation of
      topical rebamipide treatment revealed the epithelium and nevus, where numerous
      goblet cells were present (28 cells/HPF), and mucin-like substances were markedly
      secreted from the goblet cells. Topical rebamipide markedly increased the number
      of goblet cells and stimulated the secretion of mucin-like substances in the
      caruncular tissue of a human patient. These results suggest that topical
      rebamipide is useful in patients following surgery and/or biopsy to support
      tissue repair of the ocular surface.

PMID- 25574214
TI  - Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes.
AB  - Diabetic cardiomyopathy (DCM), an independent coronary heart disease that
      develops in diabetic individuals, is characterized by changes in the myocardial
      structure and function. The aim of the present study was to investigate the
      protective effect of rutin on DCM in a streptozotocin-induced diabetic rat model.
      Rutin was orally administrated at a dose of 8 mg/kg body weight. Metabolic
      profiles, myocardial enzymes and oxidative stress were examined by biochemical
      tests. The expression levels of cellular proteins associated with apoptosis were
      measured by western blot analysis, while the levels of inflammatory factors were
      assessed by immunohistochemical analyses. Rats with DCM exhibited an abnormal
      metabolic profile, aberrant myocardial enzymes, elevation of oxidative stress
      markers, increased levels of inflammatory factors and enhanced apoptotic cell
      death. Notably, rutin was shown to protect and improve myocardial dysfunction,
      oxidative stress, apoptosis and inflammation in the hearts of the diabetic rats.
      In conclusion, these results indicated that rutin may have great therapeutic
      potential in the treatment of DCM, and possibly other cardiovascular disorders,
      by preventing oxidative stress, inflammation and cell death. However, further
      detailed studies are required to reveal the exact mechanisms underlying the
      protective effect of rutin.

PMID- 25574216
TI  - Recombinant Cpn 0810 stimulates proinflammatory cytokine expression and apoptosis
      in human monocytes.
AB  - The aim of the present study was to express the recombinant Chlamydophila
      pneumoniae (C. pneumoniae) protein, Cpn 0810, in Escherichia coli (E. coli) BL21,
      and investigate the effects of Cpn 0810 on inflammatory and apoptotic processes
      in human monocytic (THP-1) cells. An ELISA was performed to detect the levels of
      the proinflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin
      (IL)-6. In addition, Hoechst 33258 staining and annexin V binding analyses were
      performed to measure the rates of apoptosis. Purified glutathione S-transferase
      (GST)-Cpn 0810 recombinant proteins were obtained from the E. coli BL21 cells
      carrying the pGEX6p-2/Cpn 0810 plasmid, and were shown to stimulate the
      expression of TNF-alpha and IL-6 in the THP-1 cells in a dose- and time-dependent
      manner. TNF-alpha and IL-6 levels peaked at 24 h after GST-Cpn 0810 stimulation.
      Furthermore, GST-Cpn 0810 significantly promoted the apoptosis of THP-1 cells. In
      conclusion, recombinant GST-Cpn 0810 was shown to stimulate the expression of TNF
      alpha and IL-6, inhibit proliferation and induce apoptosis in THP-1 cells.
      Therefore, Cpn 0810 may interact with host cells following C. pneumoniae
      infection, functioning as an important pathogenic factor.

PMID- 25574217
TI  - 'Cool and quiet' therapy for malignant hyperthermia following severe traumatic
      brain injury: A preliminary clinical approach.
AB  - Malignant hyperthermia increases mortality and disability in patients with brain
      trauma. A clinical treatment for malignant hyperthermia following severe
      traumatic brain injury, termed 'cool and quiet' therapy by the authors of the
      current study, was investigated. Between June 2003 and June 2013, 110 consecutive
      patients with malignant hyperthermia following severe traumatic brain injury were
      treated using mild hypothermia (35-36 degrees C) associated with small doses of
      sedative and muscle relaxant. Physiological parameters and intracranial pressure
      were monitored, and the patients slowly rewarmed following the maintenance of
      mild hypothermia for 3-12 days. Consecutive patients who had undergone
      normothermia therapy were retrospectively analyzed as the control. In the mild
      hypothermia group, the recovery rate was 54.5%, the mortality rate was 22.7%, and
      the severe and mild disability rates were 11.8 and 10.9%, respectively. The
      mortality rate of the patients, particularly that of patients with a Glasgow Coma
      Scale (GCS) score of between 3 and 5 differed significantly between the
      hypothermia group and the normothermia group (P<0.05). The mortality of patients
      with a GCS score of between 6 and 8 was not significantly different between the
      two groups (P> 0.05). The therapy using mild hypothermia with a combination of
      sedative and muscle relaxant was beneficial in decreasing the mortality of
      patients with malignant hyperthermia following severe traumatic brain injury,
      particularly in patients with a GCS score within the range 3-5 on admission. The
      therapy was found to be safe, effective and convenient. However, rigorous
      clinical trials are required to provide evidence of the effectiveness of 'cool
      and quiet' therapy for hyperthermia.

PMID- 25574219
TI  - Activation of autophagy and paraptosis in retinal ganglion cells after retinal
      ischemia and reperfusion injury in rats.
AB  - Glaucoma is a neurodegenerative disease characterized by elevated intraocular
      pressure (IOP), which causes retinal ischemia and progressive neuronal death.
      Retinal ischemia/reperfusion (RIR) injury is a common clinical condition
      representing the main cause of irreversible visual field defects in humans. The
      aim of this study was to investigate whether non-apoptotic forms of programmed
      cell death (PCD) have an effect on RIR injury in an experimental model that
      replicates features of acute hypertensive glaucoma and to explore the possible
      underlying mechanisms. The activation of autophagy was investigated in retinal
      ganglion cells (RGCs) following RIR in comparison with a control group, using
      immunofluorescence against microtubule-associated protein 1 light chain 3 (LC3).
      RIR injury increased LC3 expression in the cytoplasm of RGCs in the ganglion cell
      layer (GCL) 6 h after the insult, and the increased expression was sustained
      throughout the experimental period. Following RIR insult, the number of neurons
      in the GCL significantly decreased. Ultra-structural analyses showed that double-
      or multiple-membrane autophagosomes were markedly accumulated in the cytoplasm of
      RGCs following IOP elevation. Since there are no known markers for paraptosis,
      its identification was based on morphological criteria. Electron microscopy (EM)
      analysis revealed severe structural alterations associated with cytoplasmatic
      vacuolization within the 6 h after RIR injury and RGC death. EM also revealed
      that vacuoles were derived predominantly from the progressive swelling of the
      endoplasmic reticulum (ER) and/or mitochondria in RGCs after RIR injury. The
      results provide novel evidence implicating an important role of autophagy and
      paraptosis in the pathogenesis of RIR injury. Autophagy and paraptosis take place
      during developmental cell death in the nervous system as well as in certain cases
      of neurodegeneration. Therefore, targeting autophagy and paraptosis could have
      therapeutic potential for the prevention of glaucoma involving RIR injury.

PMID- 25574218
TI  - Rapid identification of apolipoprotein E genotypes by high-resolution melting
      analysis in Chinese Han and African Fang populations.
AB  - Apolipoprotein E (APOE) gene polymorphism can affect APOE gene transcription,
      serum lipid levels and repair of tissue damage, which could place individuals at
      serious risk of cardiovascular disease or certain infectious diseases. Recently,
      high-resolution melting (HRM) analysis was reported to be a simple, inexpensive,
      accurate and sensitive method for the genotyping or/and scanning of rare
      mutations. For this reason, an HRM analysis was used in the present study for
      APOE genotyping in the Southern Chinese Han and African Fang populations. A total
      of 100 healthy Southern Chinese Han and 175 healthy African Fang individuals
      attended the study. Polymerase chain reaction-DNA sequencing was used as a
      reference method for the genotyping of these samples. The six APOE genotypes
      could all be rapidly and efficiently identified by HRM analysis, and 100%
      concordance was found between the HRM analysis and the reference method. The
      allele frequencies of APOE in the Southern Chinese Han population were 7.0, 87.5
      and 5.5% for E2, E3 and E4, respectively. In the African Fang population, the
      allele frequencies of APOE were 24.3, 65.7 and 10.0% for E2, E3 and E4,
      respectively. A statistically significant difference was found between the allele
      frequencies between the populations (P<0.05). In conclusion, the present study
      revealed the molecular characterization of APOE gene polymorphism in the Han
      population from the Chaozhou region of Southern China and the Fang population
      from Equatorial Guinea. The findings of the study indicated that HRM analysis
      could be used as an accurate and sensitive method for the rapid screening and
      identification of APOE genotypes in prospective clinical and population genetic
      analyses.

PMID- 25574220
TI  - Anti-fatigue activities of polysaccharides extracted from Hericium erinaceus.
AB  - Hericium erinaceus (HEP) is a notable medicinal fungus grown in China and other
      oriental countries. Polysaccharides from HEP have recently attracted considerable
      attention due to their numerous physiological activities. The objective of this
      study was to evaluate the anti-fatigue activity of HEP in a mouse model. After
      one week of acclimation, mice were randomly divided into four groups: a control
      group, a low-dose HEP-treated group, a moderate-dose HEP-treated group, and a
      high-dose HEP-treated group. The treated groups received HEP (50, 100 and 200
      mg/kg, ig), while the control group received saline solution. Following treatment
      for 28 days, the mice performed a forced swimming test until they were exhausted,
      then the exhaustive swimming time was recorded along with certain biochemical
      parameters related to fatigue, including blood lactic acid (BLA), serum urea
      nitrogen (SUN), tissue glycogen, superoxide dismutase (SOD), glutathione
      peroxidase (GPx) and malondialdehyde (MDA). These results suggested that HEP has
      significant anti-fatigue activity by decreasing BLA, SUN and MDA content, as well
      as increasing tissue glycogen content and antioxidant enzyme activity. Based on
      these results, this study provided theoretical support for the application of HEP
      in the field of sports nutrition.

PMID- 25574221
TI  - Effect of Zhuyun recipe on endometrial pinopode expression in mice with embryonic
      implantation dysfunction and ovulation stimulation.
AB  - Zhuyun recipe (ZYR) is a traditional Chinese medicine that has been widely used
      as an infertility treatment for a number of years. Although the therapeutic
      effects are desirable and satisfactory, the therapeutic mechanism of ZYR remains
      poorly understood. In the present study, pinopodes were investigated as an
      important morphological marker of endometrial receptivity, in order to further
      investigate the therapeutic mechanism of ZYR. The expression of pinopodes during
      the implantation window was observed using scanning electron microscopy in mice
      with induced ovarian stimulation (OS) and embryo implantation dysfunction (EID).
      A marked decrease in the number of fully developed pinopodes was observed on the
      endometrial surface in the OS and EID model mice, which was in accordance with
      the decreased pregnancy rate and number of embryonic implantation sites when
      compared with the control. Following treatment with ZYR, the spatial and temporal
      expression of pinopodes in the OS and EID mice was found to be similar to the
      control mice. In conclusion, ZYR was demonstrated to improve endometrial
      receptivity in OS and EID mice through significant improvements in the spatial
      and temporal expression of pinopodes.

PMID- 25574222
TI  - Intra-articular hyaluronic acid and corticosteroids in the treatment of knee
      osteoarthritis: A meta-analysis.
AB  - The aim of the present study was to evaluate the therapeutic effect of intra
      articular hyaluronic acid (HA) in comparison to corticosteroids (CS) for knee
      osteoarthritis (OA). The data sources included PubMed, EMBASE, The Cochrane
      Central Register of Controlled Trials and hand searched reviews. Randomized
      controlled trials that reported the effects of intra-articular HA and CS in the
      treatment of knee OA were selected based on specific inclusion criteria. A meta
      analysis was performed for the visual analog scale (VAS), Lequesne index, Knee
      Society Clinical Rating System (KSS), maximum flexion and adverse events of knee
      OA. Sensitivity analysis was also conducted to avoid bias. The seven eligible
      trials included 583 participants and the majority of the trials were of high
      quality. After one month, the mean difference in the VAS was 1.66 [95% confidence
      interval (CI); -0.90, 4.23), indicating equal efficacy for HA and CS. However,
      after three months, the mean difference was -12.58 (95% CI; -17.76, -7.40), while
      after six months, the difference was -9.01 (95% CI; -12.62, -5.40), favoring HA.
      For the additional indicators, including the Lequesne index, the KSS, maximum
      flexion and adverse events, no statistically significant differences were
      observed between the two treatment approaches for knee OA. Therefore, the results
      of the meta-analysis highlight a therapeutic trajectory for intra-articular HA in
      knee OA pain, as compared with CS, over six months post-intervention. After one
      month, the two approaches exhibited equal efficacy; however, in the long term, HA
      was found to have an enhanced effect. No statistically significant difference was
      observed in the adverse events caused by the two interventions. Further
      investigation and understanding into the trend observed in the present study may
      aid clinicians in the treatment of knee OA.

PMID- 25574223
TI  - Nerve growth factor for Bell's palsy: A meta-analysis.
AB  - A meta-analysis was performed to evaluate the efficacy and safety of nerve growth
      factor (NGF) in the treatment of Bell's palsy. PubMed, the Cochrane Central
      Register of Controlled Trials, Embase and a number of Chinese databases,
      including the China National Knowledge Infrastructure, China Biology Medicine
      disc, VIP Database for Chinese Technical Periodicals and Wan Fang Data, were used
      to collect randomised controlled trials (RCTs) of NGF for Bell's palsy. The span
      of the search covered data from the date of database establishment until December
      2013. The included trials were screened comprehensively and rigorously. The
      efficacies of NGF were pooled via meta-analysis performed using Review Manager
      5.2 software. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated using the fixed-effects model. The meta-analysis of eight RCTs showed
      favorable effects of NGF on the disease response rate (n=642; OR, 3.87; 95% CI,
      2.13-7.03; P<0.01; I2=0%). However, evidence supporting the effectiveness of NGF
      for the treatment of Bell's palsy is limited. The number and quality of trials
      are too low to form solid conclusions. Further meticulous RCTs are required to
      overcome the limitations identified in the present study.

PMID- 25574224
TI  - Diagnosis and treatment of adrenocorticotrophic hormone-independent macronodular
      adrenocortical hyperplasia: A report of 23 cases in a single center.
AB  - The aim of the present study was to present the treatment observations of
      patients with adrenocorticotrophic hormone (ACTH)-independent macronodular
      adrenal hyperplasia (AIMAH) from a single medical center. A total of 23 patients
      with AIMAH were retrospectively reviewed according to the clinical features of
      the patient. Physical symptoms and biochemical evidence of Cushing's syndrome
      (CS) were present in all the cases. High and low dose dexamethasone failed to
      suppress cortisone secretion on the suppression tests and ACTH levels were low in
      all the cases. Bilateral enlarged adrenal glands were observed with computed
      tomography scans in the 23 cases, which were determined to be bilateral adrenal
      macronodular hyperplasia by pathological analysis. Normal blood pressure was
      observed in eight patients in the 2-8 years following the bilateral
      adrenalectomy. A total of 15 cases underwent single side adrenalectomy and their
      blood pressures markedly decreased three years following surgery; medical
      treatment was administered to 12 of the 15 patients, while three patients
      underwent a contralateral adrenalectomy. Nelson's syndrome was not diagnosed for
      any of the cases. AIMAH has unique endocrinological, radiological and
      pathological features, presenting as an independent etiological factor of CS.
      Diagnosis of AIMAH is usually derived from pathological examination and long term
      remission may be achieved by unilateral adrenalectomy. Contralateral
      adrenalectomy should be performed in cases of recurrence, when followed with
      periodical examination of the symptoms and the serum concentration of cortisol.

PMID- 25574225
TI  - Clinical and prognostic significance of high-mobility group box-1 in human
      gliomas.
AB  - The objective of this study was to explore the expression and the clinical and
      prognostic significance of high-mobility group box-1 (HMGB1) in human gliomas.
      The expression of HMGB1 in 15 samples of normal brain tissue and 65 samples of
      different-grade glioma tissue was assayed using immunohistochemistry and western
      blot analysis. The associations between the differences in expression and
      pathology grades were analyzed statistically. Uni- and multivariate analyses were
      performed to investigate the prognostic value of HMGB1 expression and its
      expression levels. The positive rates of HMGB1 expression in normal brain and
      glioma tissue were 20.0% (3/15) and 76.9% (50/65), respectively. The expression
      of HMGB1 in glioma tissue was higher than that in normal tissue (P<0.05). The
      positive rates of HMGB1 expression in low-grade gliomas (LGGs, grades I and II)
      and high-grade gliomas (HGGs, grades III and IV) were 63.0% (17/27) and 86.8%
      (33/38), respectively, and the positive rates in HGG were higher than those in
      LGG (P=0.024). Western blot analysis showed that HMGB1 was also expressed in
      normal brain tissue. The expression levels in HGG were significantly higher than
      those in LGG (P<0.001). HMGB1-positive patients had significantly shorter overall
      survival times compared with HMGB1-negative patients (P=0.026). Increasing levels
      of HMGB1 expression significantly correlated with reduced survival times when all
      patients with glioma were considered (P=0.045). In conclusion, HMGB1 positivity
      and protein expression levels are of significant clinical and prognostic value in
      human gliomas. Detecting HMGB1 in human gliomas may be useful for assessing the
      degree of malignancy, and HMGB1 would appear to be a promising target in the
      clinical management of patients with glioma.

PMID- 25574226
TI  - Brain-derived neurotrophic factor gene-modified bone marrow mesenchymal stem
      cells.
AB  - The present study aimed to investigate the effects of human brain-derived
      neurotrophic factor (hBDNF) on the differentiation of bone marrow mesenchymal
      stem cells (MSCs) into neuron-like cells. Lentiviral vectors carrying the hBDNF
      gene were used to modify the bone marrow stromal cells (BMSCs) of Sprague-Dawley
      (SD) rats. The rat BMSCs were isolated, cultured and identified. A lentivirus
      bearing hBDNF and enhanced green fluorescent protein (eGFP) genes was subcultured
      and used to infect the SD rat BMSCs. The expression of eGFP was observed under a
      fluorescence microscope to determine the infection rate and growth of the
      transfected cells. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) was used to
      detect the proliferation rate of cells following transfection. Reverse
      transcription quantitative polymerase chain reaction (RT-qPCR) and western blot
      analysis were used to detect the expression levels of hBDNF. Differentiation of
      neuron-like cells was induced in vitro and the differentiation rate of the
      induced neural-like cells was compared with that in control groups and analyzed
      statistically. In the cultured cells, flow cytometry demonstrated positive
      expression of cluster of differentiation (CD)90 and CD44, and negative expression
      of CD34 and CD45. The proliferation rate of the rat BMSCs increased following
      gene transfection. The expression of hBDNF-eGFP was detected in the BMSCs of the
      experimental group. The differentiation rate of hBDNF-modified cells into neuron
      like cells in the experimental group was higher compared with that in empty
      plasmid and untransfected negative control groups. The difference was
      statistically significant (P<0.05). Thus, BDNF gene transfection is able to
      promote the differentiation of BMSCs into neuron-like cells. BDNF may play an
      important role in the differentiation of MSCs into neuron-like cells.

PMID- 25574227
TI  - Diagnosis and treatment of a dural arteriovenous fistula presenting with
      progressive parkinsonism and dementia: A case report and literature review.
AB  - A dural arteriovenous fistula (DAVF) presenting with parkinsonism and dementia is
      rare; thus, is easily misdiagnosed. The present study reports the case of a 62
      year-old male with mobility disabilities and a cognitive disorder. The initial
      symptoms were progressive symmetrical limb stiffness and weakness without
      significant limb tremor, and subsequently the appearance of progressive memory
      loss, behavioral abnormalities and a decline in the activities of daily living.
      Cranial magnetic resonance imaging (MRI) revealed an enlarged vascular shadow at
      the meninges of the left temporal lobe. In addition, digital subtraction
      angiography (DSA) revealed a DAVF in the left temporal region, fed by the
      bilateral middle meningeal arteries and meningeal branches of the vertebral
      artery, which were enlarged abnormally, with poor venous reflux to the superior
      sagittal sinus. The patient was treated with transarterial embolization therapy.
      Intraoperative angiography showed almost complete embolization of the DAVF. At
      day 3 following the surgery, the muscle tension of the bilateral limbs decreased
      significantly. After two weeks, the memory ability of the patient had recovered
      to the level prior to the onset, and the gait was stable. At one month post
      surgery, the patient was able to take care of himself completely, and after three
      months, a stereotactic treatment was conducted for the residual fistula. At the
      one year follow-up, neurological examination revealed that the patient had
      recovered normally. In conclusion, progressive parkinsonism and dementia with an
      abnormal flow void shadow on cranial MRI films should be considered as a possible
      diagnosis of a DAVF. In these cases, DSA and endovascular treatment are
      recommended as soon as possible.

PMID- 25574228
TI  - Effects of monocyte-endothelium interactions on the expression of type IV
      collagenases in monocytes.
AB  - The adhesion of monocytes to endothelial cells is one of the early stages in the
      development of atherosclerosis. The expression of type IV collagenases, which
      include matrix metalloproteinase (MMP)-2 and MMP-9, in monocytes is hypothesized
      to play an important role in monocyte infiltration and transformation into foam
      cells. The aim of the present study was to examine the effects of monocyte
      endothelium interactions on the expression levels of type IV collagenases and
      their specific inhibitors in monocytes, and to investigate the roles of tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-1beta in this process. Monocytes
      were single-cultured or co-cultured with endothelial cells. The expression of the
      type IV collagenases, MMP-2 and MMP-9, and their specific inhibitors, tissue
      inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, in monocytes was determined
      by immunohistochemistry followed by image analysis. The expression levels of MMP
      2 and MMP-9 were found to be low in the single-culture monocytes, but increased
      significantly when the monocytes and endothelial cells were co-cultured. However,
      treatment with monoclonal TNF-alpha or IL-1beta antibodies partially inhibited
      the upregulated expression of MMP-2 and MMP-9 in the co-cultured monocytes.
      Expression of TIMP-1 and TIMP-2 was observed in the single monocyte culture, and
      a small increase in the expression levels was observed when the monocytes were co
      cultured with endothelial cells. Therefore, monocyte-endothlium interactions were
      shown to increase the expression of type IV collagenases in monocytes, resulting
      in the loss of balance between MMP-2 and -9 with TIMP-1 and -2. In addition, TNF
      alpha and IL-1beta were demonstrated to play important roles in this process.

PMID- 25574229
TI  - Antioxidative and antiatherogenic effects of flaxseed, alpha-tocopherol and their
      combination in diabetic hamsters fed with a high-fat diet.
AB  - Oxidative stress has previously been shown to play a role in the pathogenesis of
      diabetes mellitus (DM) and its complications. In the present study, the effects
      of supplementation with dietary antioxidants, flaxseed and alpha-tocopherol were
      investigated in diabetic golden Syrian hamsters fed with a high-fat diet. Thirty
      five golden Syrian hamsters were randomly divided into a control group (C) and
      four diabetic groups (DM, DM + flax, DM + E and DM + Flax + E). The hamsters
      received four different diets for a 20-week period, as follows: i) Groups C and
      DM received a high-fat diet (40% energy as fat), deficient in alpha-linolenic
      acid (ALA); ii) the DM + Flax group received a high-fat diet enriched with ground
      flaxseed 15 g/100 g of food, rich in ALA; iii) the DM + E group received a high
      fat diet enriched with vitamin E, 40 mg alpha-tocopherol/100 g of food; and iv)
      the DM + Flax + E group received a high-fat diet enriched with flaxseed and
      vitamin E. The results of serum lipid and oxidative stress analysis suggested
      that the antiatherogenic effect of flaxseed, alpha-tocopherol and their
      combination added to a high-fat diet in diabetic hamsters was based primarily on
      their antioxidative role, demonstrated by decreased serum lipid peroxidation and
      increased liver glutathione content. Improvements of serum glucose and non-high
      density lipoprotein cholesterol (HDL-C) levels were observed and may have
      contributed to the prevention of diabetic macroangiopathy evidenced in the
      histopathological examination. The antioxidant effect of flaxseed was similar to
      that of alpha-tocopherol in diabetic hamsters fed a high-fat diet and combined
      supplementation did not appear to bring more benefits than flaxseed alone.
      Moreover, the high dose of ground flaxseed alone may have a better
      cardioprotective effect than alpha-tocopherol in diabetic hamsters by reducing
      total cholesterol and non-HDL-C levels and increasing HDL-C levels.

PMID- 25574230
TI  - Effect of ambroxol on the concentration of cefotaxime in the bronchoalveolar
      lavage fluid of rats with pulmonary fibrosis.
AB  - This study aimed to investigate the effect of ambroxol on the concentration of
      cefotaxime in the bronchioalveolar lavage fluid of rats with bleomycin-induced
      pulmonary fibrosis. A total of 54 Wistar male rats were randomly divided into
      three groups, namely the normal control group, model group and ambroxol group. On
      experimental day 0, the rats were intratracheally instilled with bleomycin (5
      mg/kg body weight) or sterile saline. The rats in the ambroxol group were then
      treated with ambroxol (35 mg/kg/day) intraperitoneally. On days 7, 14, 28 after
      instillation, six rats from each group were sacrificed, bronchial alveolar fluids
      were recovered and the lungs were collected for histopathological examination
      following the injection of cefotaxime (600 mg/kg) intravenously. The
      concentration of cefotaxime in the bronchial alveolar fluids was assayed by a
      liquid chromatography-mass spectrometry method. On day 7, the concentration of
      cefotaxime in the bronchial alveolar fluid of the ambroxol group was lower than
      that of the model group. On day 14, the concentration of cefotaxime in the
      bronchial alveolar fluids of the ambroxol group was higher than that of the model
      group, and the difference between these groups was significant statistically
      (P<0.001). On day 28, the concentration of cefotaxime in the bronchial alveolar
      fluids of the ambroxol group decreased sharply, and was lower than that of the
      model group (P=0.126). These results indicate that ambroxol increased the
      concentration of cefotaxime in the bronchial alveolar fluids at the primary
      fibrosis stage.

PMID- 25574231
TI  - Correlation between nuclear factor kappaB activity and pulmonary artery pressure
      in a rat high pulmonary blood flow model.
AB  - The aim of the present study was to investigate the correlation between nuclear
      factor-kappaB (NF-kappaB) activity and pulmonary artery pressure in the pulmonary
      artery endothelial cells of high pulmonary blood flow rat models. A total of 50
      four-week-old male Wistar rats were randomly divided into four groups: Surgery
      shunt group (Tn, n=15); surgery + pyrollidine dithiocarbamate (PDTC)
      administration group (Ti, n=15); sham control group (Co, n=10) and negative
      control group (Cn, n=10). The 30 rats of the Ti and Tn groups underwent carotid
      artery-external jugular vein anastomosis; the 15 rats in the Ti group were
      injected with PDTC intraperitoneally 1 h prior to surgery for a two-week
      continuous infusion. After 12 weeks of feeding ad libitum, right ventricular
      systolic pressure and NF-kappaB activity in the pulmonary artery endothelial
      cells of the rats were measured. The NF-kappaB activity of the Tn group was
      significantly higher than that of the Cn group (P<0.01) and the NF-kappaB
      activity of the Ti group was lower than that of the Cn group (P<0.01); however,
      no significant difference was observed between the Co and Cn groups. The
      increased activity of NF-kappaB was an important factor in the pulmonary
      vasoconstriction and structural remodeling of rats with high pulmonary blood
      flow.

PMID- 25574232
TI  - Tumor necrosis factor-alpha suppresses the protein fractional synthesis rate of
      the small intestine stimulated by glutamine in rats.
AB  - The objective of this study was to examine whether and how TNF-alpha affects
      glutamine-enhanced protein synthesis and the expression of the amino acid
      transporter ASCT2 in the small intestine at the mRNA and protein levels. A total
      of 30 male Sprague-Dawley rats were randomly assigned into three groups, namely
      the total parenteral nutrition (TPN; control), glutamine-treated (Gln), and
      glutamine- and tumor necrosis factor-alpha (TNF-alpha)-treated (TNF-alpha)
      groups. At 30 min prior to examination, all rats were mainlined with [L
      15N]leucine. The concentration of TNF-alpha in plasma and of glutamine in plasma
      and the small intestine was measured. The fractional synthesis rate (FSR) of
      protein and the mRNA and protein expression levels of ASCT2 in the small
      intestine were assessed. The level of TNF-alpha was highest in the TNF-alpha
      group and the glutamine concentration was elevated to a greater extent in the TNF
      alpha group than in the other two groups. However, the FSR of protein in the
      small intestine was significantly higher in the Gln group compared with that in
      the TNF-alpha group. The mRNA and protein expression levels of ASCT2 in the
      experimental groups were significantly higher that those in the control group,
      but did not differ significantly between the Gln and TNF-alpha groups. These
      results indicate that TNF-alpha may attenuate glutamine-stimulated protein
      synthesis in the small intestine in the early stage of sepsis in rats. The
      mechanism may be that TNF-alpha inhibits the function of the glutamine
      transporter in the uptake the glutamine into target cells for protein synthesis.
      This inhibition may occur at or following protein translation.

PMID- 25574234
TI  - Erythropoietin protects lipopolysaccharide-induced renal mesangial cells from
      autophagy.
AB  - The aim of this study was to investigate the effects of erythropoietin (EPO) on
      the impairment of autophagy induced by lipopolysaccharide (LPS) in primary
      cultured rat glomerular mesangial cells (GMCs). Rat GMCs were isolated and
      cultured in normal glucose, high-glucose, LPS or LPS + EPO medium. At 24 and 72 h
      of culture, the cells were examined for expression levels of the autophagy
      markers LC3 and p62/sequestosome-1 (SQSTM1) using western blot analysis. At 24 h,
      no significant difference in the expression of LC3 and p62/SQSTM1 was observed
      among the groups; however, the cells exposed to high-glucose medium for 72 h
      showed downregulated LC3 expression and upregulated p62/SQSTM1 expression. The
      cells exposed to LPS (10 ng/ml) for 72 h showed upregulated LC3 expression and
      upregulated p62/SQSTM1 expression. These changes were reversed in the LPS + EPO
      group at 72 h. In conclusion, EPO can inhibit LPS-induced autophagy in rat GMCs.

PMID- 25574233
TI  - Excessive levels of nitric oxide in rat model of Parkinson's disease induced by
      rotenone.
AB  - Systemic rotenone models of Parkinson's disease (PD) are highly reproducible and
      may provide evidence on the pathogenesis of PD. In the present study, male
      Sprague-Dawley rats (1-year-old) were subcutaneously administered with rotenone
      (1.5 mg/kg/day) for six days and observed for the following three weeks. Compared
      with the control rats, a significant decrease was observed in the body weight and
      a marked increase was observed in the areas under the behavioral scoring curves
      in the rotenone-treated rats. Immunohistochemical staining revealed that the
      abundance of nigral tyrosine hydroxylase (TH)-positive neurons was markedly
      reduced following rotenone treatment. ELISA and neurochemical assays demonstrated
      a significant increase in the levels of nitric oxide (NO) and NO synthase,
      whereas a marked decrease was observed in the thiol levels in the brains of the
      rotenone-treated rats. Thus, subacute rotenone treatment was found to induce
      behavioral deficits and the loss of nigral TH-positive neurons which may be
      associated with the excessive levels of NO in the rat brains.

PMID- 25574235
TI  - Preventive effect of Dendrobium candidum Wall. ex Lindl. on activated carbon
      induced constipation in mice.
AB  - The aim of this study was to investigate the effects of Dendrobium candidum Wall.
      ex Lindl. (D. candidum) on activated carbon-induced constipation in ICR mice. ICR
      mice were orally administered D. candidum for 9 days. Body weight, defecation
      status, gastrointestinal (GI) transit and defecation times, in addition to the
      levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS),
      acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide
      (VIP) in serum were used to evaluate the preventive effects of D. candidum on
      constipation. The laxative drug bisacodyl acted as a positive control. The time
      to the first defecation of a black stool for the normal, control, bisacodyl
      treated (100 mg/kg), 200 and 400 mg/kg D. candidum-treated mice was 84, 202, 126,
      161 and 142 min, respectively. Following the consumption of 200 and 400 mg/kg D.
      candidum or bisacodyl (100 mg/kg), the GI transit was reduced to 57.7, 74.6 and
      90.2%, respectively, of the transit in normal mice. The serum levels of MTL, Gas,
      ET, AChE, SP and VIP were significantly increased and the serum levels of SS were
      reduced in the mice treated with D. candidum compared with those in the untreated
      control mice (P<0.05). These results demonstrate that D. candidum has preventive
      effects on constipation in mice, and a greater functional activity was observed
      when a higher concentration was administered.

PMID- 25574236
TI  - Effects of azithromycin on Pseudomonas aeruginosa isolates from catheter
      associated urinary tract infection.
AB  - Pseudomonas aeruginosa is a common pathogenic bacterium in urinary tract
      infections (UTIs), particularly catheter-associated UTIs. The aim of this study
      was to investigate the effect of azithromycin (AZM) on P. aeruginosa isolated
      from UTIs. Isolates were identified by biochemical assays and the Vitek system.
      Antimicrobial susceptibility was determined using the disk diffusion assay.
      Biofilm formation and adhesion were assayed using a crystal violet staining
      method. The swimming motility was assayed on agar plates. The elastase activity
      and rhamnolipid production were determined by the elastin-Congo red method and
      orcinol reaction, respectively. A total of 32 bacterial isolates were collected
      from 159 urinary catheters and eight of them were P. aeruginosa isolates. The
      results showed that the P. aeruginosa isolates had stronger biofilm formation
      capability and the biofilms were thicker than those of P. aeruginosa PAO1. AZM
      inhibited biofilm formation and adhesion on urinary catheters, and also decreased
      swimming motility and the production of virulence factors. The results of this
      study indicated that AZM is potentially a good choice for use in the treatment of
      UTIs.

PMID- 25574237
TI  - Effects of the Treg/Th17 cell balance and their associated cytokines in patients
      with hepatitis B infection.
AB  - The extent to which T-cell-mediated immunity is impaired in patients with
      hepatitis B virus (HBV) infection remains controversial. In addition, the role of
      T regulatory (Treg) and T helper 17 (Th17) cells and their associated cytokines
      in immunity is not clear. In the present study, peripheral blood samples were
      collected from 44 patients with chronic hepatitis B virus, 14 asymptomatic
      hepatitis B carriers, 19 patients with liver cirrhosis and 20 healthy
      individuals. Flow cytometry was used to detect the percentages of T cell subsets
      in the samples, including CD3+, CD4+ and CD8+ T cells, Treg cells and Th17 cells.
      A cytometric bead array was conducted to detect the levels of interleukin (IL)
      17, -6, -10 and -21, and transforming growth factor (TGF)-beta. The data revealed
      that Treg cell levels decreased, while Th17 cell levels increased in the
      peripheral blood of HBV patients. As the extent of inflammation and fibrosis in
      the hepatic tissue increased, the frequency of Treg and Th17 cells in the
      peripheral blood did not significantly differ. In addition, the levels of Th17
      cells were found to positively correlate with TGF-beta and IL-21 levels.
      Therefore, analyzing the balance between Treg/Th17 cells and their associated
      cytokines may be a useful indicator in the diagnosis of HBV.

PMID- 25574238
TI  - microRNA-148a inhibits hepatocellular carcinoma cell invasion by targeting
      sphingosine-1-phosphate receptor 1.
AB  - microRNA (miR)-148a has been shown to act as an important suppressor in numerous
      human malignancies and is markedly downregulated in hepatocellular carcinoma;
      however, the role of miR-148a in the regulation of hepatocellular carcinoma cell
      invasion, as well as the underlying mechanism, has never been studied. In the
      present study, the expression level of miR-148a was found to be significantly
      decreased in hepatocellular carcinoma tissues and HepG2 cells when compared with
      that in the normal adjacent tissues. Furthermore, a novel target of miR-148a was
      found, sphingosine-1-phosphate receptor 1 (S1PR1), whose expression was
      negatively regulated by miR-148a at a post-transcriptional level in
      hepatocellular carcinoma HepG2 cells. Upregulation of miR-148a by transfection
      with miR-148a mimics notably suppressed HepG2 cell invasion, similar to the
      effect of the SIPR1 downregulation induced by SIPR1-specific small interfering
      RNA, while the restoration of S1PR1 expression reversed the inhibitory effect of
      miR-148a upregulation on HepG2 cell invasion. Accordingly, the current study
      suggests that miR-148a plays an inhibitory role in the regulation of
      hepatocellular carcinoma cell invasion by directly targeting S1PR1.

PMID- 25574239
TI  - Effect of alpha-tocopheryl succinate on the molecular damage induced by
      indomethacin in C6 glioma cells.
AB  - Indomethacin is a member of the non-steroidal anti-inflammatory drug (NSAID)
      class, which has great potential for use in the treatment of glioma. However, it
      induces the generation of reactive oxygen species (ROS) and causes molecular
      damage while inducing its effects. Vitamin E is widely used in the complementary
      therapy of cancers. The main goal of the present study was to investigate the
      effects of alpha-tocopheryl succinate (alpha-TOS) against the oxidative damage
      induced by indomethacin in C6 glioma cells. Cells were treated with 10 MUM alpha
      TOS alone or in combination with 200 MUM indomethacin for two days. The
      intracellular ROS level, molecular damage as revealed by lipid peroxidation and
      protein carbonyl formation, and the COX activity in C6 glioma cells were
      measured. Treatment of the cells with alpha-TOS and indomethacin, alone or in
      combination, caused the levels of ROS generation and protein damage to increase,
      but protected against lipid peroxidation and reduced COX activity.

PMID- 25574240
TI  - Dynamic changes of early-stage aortic lipid deposition in chronic renal failure
      rats and effects of decorin gene therapy.
AB  - The aim of the present study was to clarify the association between lipid
      metabolism and the atherosclerosis in early-stage chronic renal failure at the
      molecular level and to explore the efficacy of decorin on chronic renal failure.
      Sprague Dawley rats receiving 5/6 nephrectomy and Sham surgery were divided into
      control and experimental groups. Sprague Dawley rats receiving 5/6 nephrectomy
      were divided into control and experimental groups, and the experimental group was
      further subdivided into rats receiving treatment with fibroblasts (FBs)
      transfected either with empty vector and with a decorin (DCN) gene. The dynamic
      levels of triglyceride (TG), total cholesterol (T-Ch) and total phospholipid (T
      PL) were detected on the 10th, 30th and 60th days. The body weight, blood lipid
      levels, renal function and renal tissue were observed after four weeks, and
      transforming growth factor-betal and protein expression was detected by
      immunohistochemistry. In total, 4 weeks after treatment, the DCN expression in
      the renal tissue of rats treated with DCN-transfected FBs was significantly
      increased compared to that in the control rats. The results showed that the
      levels of the three lipids in the aortic arches were slightly elevated on the
      10th day compared with those in the control group, and the TG level was
      significantly increased on the 30th day. The levels of T-Ch, TG and T-PL in the
      aortic arches were significantly elevated on the 60th day. The TG and T-Ch levels
      in the plasma and aortic tissues of Sprague Dawley rats receiving 5/6 nephrectomy
      without any treatment and after receiving treatment with FBs transfected with
      empty vector were significantly increased compared with those in the control
      group. The increased T-Ch and decreased T-PL levels in the erythrocyte membrane
      increased the rigidity of the erythrocyte and decreased erythrocyte
      deformability. In conclusion, highly expressed DCN mitigated renal fibrosis and
      thus delayed renal failure as well as mitigating the abnormal lipid metabolism of
      the chronic renal failure.

PMID- 25574241
TI  - Impacts of leukocyte filtration and irradiation on coagulation factors in fresh
      frozen plasma.
AB  - This study aimed to compare and analyze the changes in the coagulation factors in
      fresh frozen plasma (FFP) prior to and following leukocyte filtration and
      irradiation. In total, 30 bags of FFP from healthy donors were processed: One
      third of the FFP of each bag was left within the original bag (the A group), the
      other two-thirds of the FFP of each bag were passed through a disposable
      leukocyte filter, then divided equally into two parts. One of these was
      designated as the B group, and the other was designated the C group (subjected to
      30 Gy irradiation). All samples were analyzed to evaluate 16 coagulation
      indicators. Analysis of variance revealed that there were statistically
      significant differences in the levels of fibrinogen (FbgC) and coagulation factor
      VIII (FVIII:C) among the groups (P=0.044 and P=0.015, respectively); the
      Dunnett's t-test revealed that there was a statistically significant difference
      in the level of FbgC between the A and B groups (P=0.025), and there was a
      statistically significant difference in the level of FVIII:C between the A and C
      groups (P=0.009); while the remaining 14 coagulation parameters were not
      significantly different among the groups. Although the levels of FbgC and FVIII:C
      in the FFP were reduced following treatment, this would not affect the clinical
      effect of the FFP.

PMID- 25574242
TI  - Association of various risk factors with prognosis and hospitalization cost in
      Chinese patients with acute myocardial infarction: A clinical analysis of 627
      cases.
AB  - Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality
      in the developed world and is becoming increasingly more common in developing
      countries. The risk factors affecting the prognosis of Chinese patients may
      differ from those in other populations. This study was conducted to investigate
      the potential risk factors that may correlate with prognosis and hospitalization
      costs of Chinese AMI patients. A total of 627 hospitalized AMI patients were
      recruited and their general information and relevant laboratory parameters were
      collected. Accordingly, the patients were grouped into different subgroups and
      potential risk factors and their correlations with prognosis and hospitalization
      costs were analyzed. Age, high blood pressure, infarct location and percutaneous
      coronary intervention (PCI) were the variables significantly associated with the
      differences in the prognosis of AMI patients (P<0.05), whereas times and duration
      of hospitalization, high blood pressure, infarct location and PCI treatment were
      found to be significantly associated with the cost of hospitalization (P<0.05).
      However, the AMI patients enrolled in this study may not be representative of all
      AMI patients in China. In addition, the prognosis of these patients was limited
      to their hospital stay. Therefore, long-term follow-up requires careful
      assessment.

PMID- 25574243
TI  - Effect of intensive insulin therapy on first-phase insulin secretion in newly
      diagnosed type 2 diabetic patients with a family history of the disease.
AB  - Intensive insulin treatment is known to improve beta-cell function in the
      majority of patients with newly diagnosed type 2 diabetes mellitus (T2DM), and
      family history (FH) is known to be an important independent risk factor for T2DM.
      Thus, the aim of the present study was to investigate the difference in first
      phase insulin secretion and the effect of intensive insulin therapy on the
      improvement of beta-cell function between T2DM patients with and without a FH of
      diabetes. Patients with newly diagnosed T2DM and healthy controls were divided
      into groups according to their FH of diabetes. Improvement in beta-cell function
      was evaluated with an arginine stimulation test after two weeks of continuous
      subcutaneous insulin infusion (CSII). Compared with the control group, the level
      of fasting insulin and the homeostasis model assessment of insulin resistance
      (HOMA2-IR) were higher in the DM group, while the homeostasis model assessment of
      beta-cell insulin secretion (HOMA2-%beta) and the first-phase peak ratio were
      lower (P<0.05). In addition, the first-phase peak ratio in the FH- control group
      was higher compared with that in the FH+ control group (P=0.023). Following CSII,
      all the patients achieved excellent blood glucose control in 6.2+/-3.6 days,
      without severe adverse effects. In the DM groups, the fasting insulin level and
      HOMA2-IR were lower, while the HOMA2-%beta and first-phase peak ratio were
      higher, when compared with the values prior to treatment, particularly in the FH-
      DM group. The HOMA2-%beta in the FH+ DM group was lower compared with the FH- DM
      group (P=0.027). Therefore, T2DM patients with and without a FH of the disease
      were shown to have a good response to CSII in the improvement of insulin
      resistance and beta-cell function; however, the improvements were less
      significant in patients with a FH compared with patients without a FH of
      diabetes.

PMID- 25574244
TI  - Effect of extractions from Ephedra sinica Stapf on hyperlipidemia in mice.
AB  - The aim of the present study was to investigate the hypolipidemic and antioxidant
      potential of ephedra extractions in diet-induced hyperlipidemic mice. Mice were
      fed a diet high in fat to establish the hyperlipidemic model. A total of 48 mice
      were randomly divided into six groups, which included the normal control, model
      control, positive control, ephedra alkaloid, ephedra polysaccharide and ephedra
      non-alkaloid groups. Intragastric administration of the respective treatments was
      provided continuously for four weeks and the body weight was recorded weekly. The
      total levels of cholesterol (TC), triglycerides (TG), high-density lipoprotein
      cholesterol (HDL-C) and malondialdehyde (MDA), and the activity levels of
      superoxide dismutase (SOD), alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) in the serum were recorded. In addition, changes in liver
      morphology and organ coefficients (ratio of organ to body weight) were evaluated,
      while the acute toxicity reactions of ephedra extractions were investigated using
      the modified Spearman-Karber method. Compared with the mice in the model control
      group, the weight, liver coefficient, serum levels of TC, TG and MDA, and
      activities of ALT and AST were significantly lower (P<0.05) in the mice in the
      ephedra non-alkaloid group. However, the level of HDL-C and the activity of SOD
      were markedly higher (P<0.05). Fatty degeneration of the liver in the ephedra
      alkaloid and non-alkaloid groups was notably improved compared with the model
      control group. The mean lethal dose (LD50) of ephedra alkaloids was 610 mg/kg,
      and the maximum tolerated dose of oral ephedra non-alkaloids in the mice was
      367.5-fold larger than the clinical dosage in humans. In conclusion, ephedra non
      alkaloids have therapeutic potential for the treatment of hyperlipidemia, since
      they are able to improve lipid metabolism and are relatively safe for use under
      the maximum tolerated dose.

PMID- 25574245
TI  - Efficacy and safety of a mammalian target of rapamycin inhibitor in pediatric
      patients with tuberous sclerosis complex: A systematic review and meta-analysis.
AB  - Inhibitors of mammalian target of rapamycin (mTOR) are increasingly used as
      therapy for pediatric patients with tuberous sclerosis complex (TSC). The
      uncertainty over the efficacy and safety of mTOR inhibitor therapy for the
      treatment of pediatric patients with TSC emphasizes the necessity for a synthesis
      of existing evidence. The aim of this study was to assess the efficacy and safety
      of mTOR inhibitor therapy for the treatment of pediatric patients with TSC. The
      PubMed, EmBase and Cochrane Library electronic databases were searched, and
      studies of mTOR inhibitor therapy and non-mTOR inhibitor therapy in pediatric
      patients with TSC (<18 years old) were selected. Eleven studies met the inclusion
      criteria. There was evidence of a significantly increased response rate in
      pediatric patients with TSC treated with mTOR inhibitor therapy compared with
      those treated with non-mTOR inhibitor therapy (odds ratio, 24.71; 95% confidence
      interval, 7.46-81.72; P<0.001). The majority of studies reported few adverse
      events. There was an increased incidence of mouth ulceration, stomatitis,
      convulsion and pyrexia in pediatric patients with TSC treated with mTOR inhibitor
      therapy. In conclusion, mTOR inhibitor therapy is an efficacious and safe
      treatment for pediatric patients with TSC.

PMID- 25574246
TI  - Effect of valsartan on atrial fibrillation recurrence following pulmonary vein
      isolation in patients.
AB  - Pulmonary venous isolation has emerged as an effective therapy for atrial
      fibrillation (AF); however, AF recurrence is common. The aim of the present study
      was to investigate the effect of angiotensin receptor blockers (ARBs) on the
      recurrence rate of AF following ablation therapy. In total, 120 patients, who
      were scheduled for ablation, were randomly selected. The patients were randomly
      divided into three groups, which received treatment with a placebo (n=40), 80 mg
      valsartan daily (n=40) or with 160 mg valsartan daily (n=40). The demographic
      characteristics, comorbidities, AF type and information regarding treatment with
      ARBs were recorded and analyzed. Following a mean follow-up period of 13.8+/-8.6
      months, 66.7% of patients were found to be free of AF. Kaplan-Meier analysis of
      the time until the first recurrence during the follow-up period revealed that
      patients treated with 160 mg/day valsartan presented a higher probability of
      remaining free of AF (88%, vs. 47% for the control and 65% for the 80 mg/day
      valsartan groups). In addition, multivariate analysis demonstrated that treatment
      with ARB was associated with lower AF recurrence rates (hazard ratio, 0.46; 95%
      confidence interval, 0.20-0.93] P=0.01). In conclusion, treatment with 160 mg/day
      valsartan markedly reduced the risk of recurrence of AF in a dose-dependent
      manner in AF patients following ablation.

PMID- 25574247
TI  - Clinical and morphological aspects of gray matter heterotopia type developmental
      malformations.
AB  - BACKGROUND: Gray matter heterotopia (GMH) is a malformation of the central
      nervous system characterized by interruption of normal neuroblasts migration
      between the 7(th) and 16(th) week of fetal development. The aim of the study was
      the analysis of clinical symptoms, prevalence rate and the most common concurrent
      central nervous system (CNS) developmental disorders as well as assessment of
      characteristic morphological changes of gray matter heterotopia in children
      hospitalized in our institution between the year 2001 and 2012. MATERIAL/METHODS:
      We performed a retrospective analysis of patients' data who were hospitalized in
      our institution between the year 2001 and 2012. We assessed clinical data and
      imaging exams in children diagnosed with gray matter heterotopia confirmed in MRI
      (magnetic resonance imaging). RESULTS: GMH occurred in 26 children hospitalized
      in our institution between the year 2001 and 2012. Among children with gray
      matter heterotopia most common clinical symptoms were: epilepsy, intellectual
      disability and hemiparesis. The commonest location of heterotopic gray matter
      were fronto-parietal areas of brain parenchyma, mostly subependymal region. Gray
      matter heterotopia occurred with other developmental disorders of the central
      nervous system rather than solely and in most cases it was bilateral.
      Schizencephaly and abnormalities of the corpus callosum were the most often
      developmental disorders accompanying GMH. CONCLUSIONS: 1. Subependymal gray
      matter heterotopia was more common than subcortical GMH. Subependymal GMH showed
      tendency to localize in the region of the bodies of the lateral ventricles. The
      least common was laminar GMH. 2. Gray matter heterotopia occurred more often with
      other developmental disorders of the central nervous system rather than solely.
      The most frequent concurrent disorders of the central nervous system were:
      schizencephaly, developmental abnormalities of the corpus callosum, arachnoid
      cyst, abnormalities of the septum pellucidum and the fornix. 3. GMH foci were
      more often bilateral than unilateral. 4. In the diagnostics of cell migration
      abnormalities, gray matter heterotopia included, MR imaging remains the method of
      choice.

PMID- 25574248
TI  - Usefulness of ultrasound examinations in the diagnostics of necrotizing
      enterocolitis.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most serious disorders
      of gastrointestinal tract during neonatal period. Early diagnosis and adequate
      treatment are essential in the presence of clinical suspicion of NEC. Plain
      abdominal radiography is currently the modality of choice for initial evaluation
      of gastrointestinal tract in neonates. However, when the diagnosis is uncertain,
      abdominal ultrasound with bowel assessment might be an important complementary
      examination. The aim of the study was to evaluate usefulness of ultrasound in the
      diagnosis of NEC and its value for implementation of proper treatment.
      MATERIAL/METHODS: The data of nine neonates diagnosed with NEC, hospitalized at
      the Provincial Hospital No. 2 in Rzeszow in the period from September 2009 to
      April 2013 was retrospectively analyzed. Apart from abdominal radiography,
      abdominal ultrasound with bowel assessment was performed in all nine cases.
      Imaging findings, epidemiological data, coexisting risk factors and disease
      course were assessed. RESULTS: Most children in the group were preterm neonates.
      Findings in plain abdominal radiography were normal or nonspecific. A wider
      spectrum of findings was demonstrated in all ultrasound examinations and
      intestinal pneumatosis, a pathognomonic sign for NEC, was more frequently noted
      than in plain abdominal x-ray. Most children were treated by surgical
      intervention with resection of necrotic bowel loops and in more than half of the
      cases location of changes identified during surgery was concordant with
      ultrasonographic findings. CONCLUSIONS: Abdominal ultrasound examination might be
      helpful in the diagnosis of NEC, especially when plain abdominal radiography
      findings do not correlate with clinical symptoms. However, abdominal radiography
      is still considered the modality of choice. The range of morphological changes
      detectable on ultrasound examination is much wider than in plain abdominal
      radiography. Ultrasound examination allows for more accurate assessment of
      changes within intestines and adjacent tissues, which aids clinicians in making
      more accurate therapeutic decisions and implementing proper treatment.

PMID- 25574249
TI  - Endovascular treatment of an adolescent patient with a ruptured intracranial
      aneurysm - case report and review of literature.
AB  - BACKGROUND: The occurence of aneurysms in young patients, under 18 years of age,
      is estimated at 0.5-2% of all diagnosed aneurysms. CASE REPORT: We reported on a
      case of a 16-year-old patient with subarachnoid hemorrhage diagnosed due to a
      ruptured cerebral vessel aneurysm. The angio-CT revealed an aneurysm of the
      middle cerebral artery, in its distal branch. An ad hoc coil embolization was
      performed with angiographic success. After 6 months following the ictus, the
      patient underwent a control angiography which confirmed total occlusion of the
      aneurysm with no residual inflow. Clinical examination revealed no neurological
      deficits and the patient was rated 0 in mRS (modified Rankin Scale). CONCLUSIONS:
      In experienced departments of interventional neuroradiology the endovascular
      treatment should be the treatment of choice.

PMID- 25574250
TI  - From the Editor-in-Chief: A Look at 2014.

PMID- 25574251
TI  - Introductory comments for the scientific ethics theme.

PMID- 25574252
TI  - Teaching responsible conduct responsibly.

PMID- 25574253
TI  - Smart Teaching Matters! Applying the Research on Learning to Teaching RCR.
AB  - Requirements for educating the next generation of scientists in the responsible
      conduct of research (RCR) were published approximately 25 years ago. Over the
      years, an extensive collection of research ethics educational resources have been
      developed, most of which are available to the scientific community. We can use
      these resources to effect change in student learning about responsible and
      ethical research practices; however, research on RCR educational effectiveness
      reveals mixed results. Rather than assume ethics education is ineffective,
      perhaps we should examine whether we are making the best use of these training
      tools and resources when teaching RCR. Connecting the body of knowledge on how
      people learn with how we teach research ethics may be a solution to improving
      student-learning outcomes associated with research ethics education. This essay
      provides a brief review of the research on human learning and introduces
      practical tips for connecting evidence-based principles to RCR teaching. Next
      steps involve RCR educators planning empirical research to support the
      application of research-informed practices to teaching research ethics. 

PMID- 25574254
TI  - A Modest Proposal to Move RCR Education Out of the Classroom and into Research.
AB  - Requirements for training in responsible conduct of research have significantly
      increased over the past 25 years, but worries about the integrity of science have
      only intensified. The approach to training has relied largely on short-term
      experiences, either online or in person. Even if done well, such strategies
      remain separate from, and a negligible fraction of, the practice of research. A
      proposed alternative is to empower faculty, postdoctoral fellows, and graduate
      student leaders to foster conversations about research ethics in the research
      environment. 

PMID- 25574255
TI  - Beyond responsible conduct: taking responsibility for the responsible conduct of
      others.
AB  - A unique Responsible Conduct of Research (RCR) course was created for Ph.D.,
      M.D., and M.D./Ph.D. postdoctoral fellows and junior faculty at Northwestern
      University, some of whom had prior RCR training and some of whom did not. The
      unique feature of the course is its dual focus on learning the core elements of
      RCR and preparing participants for being responsible for guiding and monitoring
      RCR behaviors of others. These more advanced but still junior scientists are at a
      key junction where they are beginning to mentor and supervise others. A second
      unique element is a required conversation on at least two RCR topics with their
      current mentors, with a short written report, modeling explicit conversations
      about RCR prospectively. Overall response has been very positive with a high
      level of engagement. Formal and informal evaluation feedback reveals how
      participants see the value of the course and how it has shaped how they intend to
      guide others in the future. An important goal of the course is to also position
      high quality RCR and RCR training within the research environment, not just the
      classroom. 

PMID- 25574256
TI  - Feelings and ethics education: the film dear scientists.
AB  - There is an increasing body of evidence that not only cognition but also emotions
      shape moral judgment. The conventional teaching of responsible conduct of
      research, however, does not target emotions; its emphasis is on rational
      analysis. Here I present a new approach, 'the feelings method,' for incorporating
      emotions into science ethics education. This method is embodied in Dear
      Scientists, an innovative film that combines humanities with arts and works at
      the subconscious level, delivering an intense mix of music and images, contrasted
      by calm narration. Dear Scientists has struck a chord across the science,
      humanities, and arts communities-a promising sign. 

PMID- 25574257
TI  - Critical issues in the teaching of responsible writing.
AB  - In this paper I identify some of the more common, problematic writing practices
      (e.g., plagiarism, selective reporting of literature, and/or results, 'spin')
      found in traditional journal articles, along with associated variables, and
      suggest ways to correct them. The primary aim of the discussion is to emphasize
      the cultivation of transparency, excellence in scholarship, and a 'best
      practices' approach to disseminating the results of our research. 

PMID- 25574258
TI  - Aligning objectives and assessment in responsible conduct of research
      instruction.
AB  - Efforts to advance research integrity in light of concerns about misbehavior in
      research rely heavily on education in the responsible conduct of research (RCR).
      However, there is limited evidence for the effectiveness of RCR instruction as a
      remedy. Assessment is essential in RCR education if the research community wishes
      to expend the effort of instructors, students, and trainees wisely. This article
      presents key considerations that instructors and course directors must consider
      in aligning learning objectives with instructional methods and assessment
      measures, and it provides illustrative examples. Above all, in order for RCR
      educators to assess outcomes more effectively, they must align assessment to
      their learning objectives and attend to the validity of the measures used. 

PMID- 25574259
TI  - Evaluation in RCR Training-Are You Achieving What You Hope For?
AB  - This Perspective addresses the value of, and realistic approaches to,
      incorporating formal evaluation processes in Responsible Conduct of Research
      (RCR) training. It comes from the experiences of a career that has combined:
      leading research teams and directing Ph.D. and M.D./Ph.D. training; teaching RCR
      since it was first required by NIH; teaching evaluation methods to directors of
      RCR and research training programs; and serving as an external evaluator for RCR
      and research training programs. Approaches to evaluation are introduced,
      contrasting quantitative and qualitative evaluation methods, along with the
      differences between formative (process) and summative (outcome) evaluation.
      Practical and realistic approaches are presented, knowing that RCR programs
      seldom have the luxury of time and funding for extensive evaluation. Guidance is
      provided on how to make sure evaluation starts from and focuses on what the
      training is designed to achieve (in terms of knowledge, skills, attitudes, and
      behaviors) rather than just what activities are taking place or what information
      is being 'delivered.' Examples of evaluation questions that might be asked about
      RCR programs are provided, as well as approaches to answering them. 

PMID- 25574260
TI  - The integrity mindset: an obligation to ourselves and others.

PMID- 25574261
TI  - An evidence-based guide for ethics instruction.
AB  - Drawing from multiple sources of evidence, this paper updates previous
      descriptions (IOM, 2002) of measurement strategies and teaching techniques to
      promote four theoretically derived abilities thought to be necessary conditions
      for the responsible conduct of research. Data from three samples (exemplary
      professionals, professionals disciplined by a licensing board, and graduates who
      completed an ethics program designed to promote the four interrelated abilities)
      suggest that development of a moral identity that is consistent with the norms
      and values of a profession is the driving force that gives rise to ethical
      sensitivity, ethical reasoning, and ethical implementation. Evidence from the
      cited studies supports the usefulness of the theoretical model to (a) deconstruct
      summary judgments about character and see them as abilities that can be assessed
      and developed; (b) guide the design assessments that are sensitive to the effects
      of interventions; and (c) augment previous IOM recommendations for the
      development of meaningful learning activities. 

PMID- 25574263
TI  - (The Ethics of) Teaching Science and Ethics: A Collaborative Proposal.
AB  - I offer a normative argument for a collaborative approach to teaching ethical
      issues in the sciences. Teaching science ethics requires expertise in at least
      two knowledge domains-the relevant science(s) and philosophical ethics.
      Accomplishing the aims of ethics education, while ensuring that science ethics
      discussions remain grounded in the best empirical science, can generally best be
      done through collaboration between a scientist and an ethicist. Ethics as a
      discipline is in danger of being misrepresented or distorted if presented by
      someone who lacks appropriate disciplinary training and experience. While there
      are exceptions, I take philosophy to be the most appropriate disciplinary domain
      in which to gain training in ethics teaching. Science students, who must be
      prepared to engage with many science ethics issues, are poorly served if their
      education includes a misrepresentation of ethics or specific issues. Students are
      less well prepared to engage specific issues in science ethics if they lack an
      appreciation of the resources the discipline of ethics provides. My collaborative
      proposal looks at a variety of ways scientists and ethicists might collaborate in
      the classroom to foster good science ethics education. 

PMID- 25574264
TI  - The Role of Philosophers in RCR Training.

PMID- 25574262
TI  - Cross-cultural considerations in U.S. research ethics education.
AB  - Demand among graduate and postdoctoral trainees for international research
      experience brings together students and investigators from increasingly diverse
      cultural backgrounds around the world. Educators in research ethics and
      scientific integrity need to address the cultural aspects of both science and
      ethics to help all trainees learn ethical practices for effective collaboration
      with a diverse array of partners. NIH and NSF's mandates for instruction in the
      responsible conduct of research do not specifically address the needs of
      international trainees or U.S. trainees who undertake research projects abroad.
      Nonetheless, research ethics educators' typical focus on policy and professional
      standards can offer trainees and faculty investigators helpful insights into
      differing ethical values and priorities in research. Examination of linguistic
      differences can also reveal important conceptual frameworks that shape ethical
      practice. New resources for teaching research integrity in cross-cultural
      settings can be a valuable addition to the development of shared understanding of
      the goals of scientific research.

PMID- 25574265
TI  - How journals and institutions can work together to promote responsible conduct.

PMID- 25574266
TI  - How should journal editors respond to cases of suspected misconduct?
AB  - Journals and institutions have important complementary roles to play in cases of
      suspected research and publication misconduct. Journals should take
      responsibility for everything they publish and should alert institutions to cases
      of possible serious misconduct but should not attempt to investigate such cases.
      Institutions should take responsibility for their researchers and for
      investigating cases of possible misconduct and for ensuring journals are informed
      if they have published unreliable or misleading articles so that these can be
      retracted or corrected. Journals and institutions should have policies in place
      for handling such cases and these policies should respect their different roles. 

PMID- 25574268
TI  - Authorship guidelines and actual practice: are they harmonized in different
      research systems?

PMID- 25574267
TI  - What studies of retractions tell us.
AB  - The retraction is receiving a growing amount of attention as an important event
      in scientific and scholarly publishing. Not only are some journals becoming
      increasingly open in their handling of the articles they withdraw-allowing
      researchers to gain important insights into the work of their colleagues-but
      scholars, too, have greater access to the reasons for retractions, information
      that is dramatically reshaping our understanding of such events. As this article
      will demonstrate, recent research has inverted the accepted lore about why
      retractions happen and their impact. 

PMID- 25574269
TI  - Science and money: problems and solutions.

PMID- 25574270
TI  - The Interrelationship between Research Integrity, Conflict of Interest, and the
      Research Environment.
AB  - Quite distinct regulatory measures have been established to try to deal with
      research misconduct and conflict of interest. To decrease research misconduct,
      the emphasis has been on education aimed at promoting an understanding of and
      commitment to research integrity. To decrease the impact of conflict of interest,
      the emphasis has been on management of the research environment. In this essay I
      discuss the idea that research misconduct and its close relative "questionable
      research practices" should be framed in the context of conflict of interest. If
      we take seriously the implication of conflict of interest regulations that even a
      $5,000 financial interest might bias the design, conduct, or reporting of
      research, then how much more risk of bias will be in play when what is at stake
      is ongoing funding of short-term research grants on which a researcher's salary
      and job depend? Education is important and necessary to promote research
      integrity but by itself will not be sufficient. Placing problems of research
      misconduct and questionable research practices in the context of conflict of
      interest makes it clear that we also will need to develop new approaches to
      manage the structure of the research environment. One example of such a
      management strategy would be for NIH to phase in a limit on the overall
      percentage of a faculty member's salary permitted to be supported with NIH grant
      funds, complementing the already existing upper dollar limit that can be used for
      faculty salaries. 

PMID- 25574271
TI  - Rethinking the Meaning of Ethics in RCR Education.
AB  - Training in the responsible conduct of research (RCR) is meant to ensure that
      federally funded scientists have the knowledge, skills, and resources necessary
      to conduct science in line with agreed upon scientific norms and ethical
      principles. At its institutional best, RCR education begins early, with
      reinforcement in subsequent stages of career development. Studies suggest,
      however, that scientists perceive the push to think about ethical matters
      negatively, narrowly equating ethics with burdensome oversight and regulation, or
      with controversies in a few highly charged areas. For their part, RCR instructors
      contribute to this narrow conception of ethics education by placing
      disproportionate emphasis on the misconduct of the few and its career-destroying
      consequences. The result is an ethics that is both individualistic and
      uncritical, an ethics incapable of explaining the threat to scientific integrity
      posed by a rigidly hierarchical distribution of power, severe competition for
      funding, a "winner takes all" credit system, and many other features of ordinary
      science. What is needed is a broader, richer conception of ethics, one that
      focuses not only on individual instances of misconduct, but also on the growing
      gap between the normative ideals of science and its institutional reward systems.

PMID- 25574272
TI  - Socially responsible science is more than "good science".
AB  - The role of scientist carries an array of responsibilities. The most obvious is
      accurate and reliable research that can be depended upon by fellow researchers.
      Scientists also have a responsibility to oppose misuse or abuse in the
      application of research findings, and to attend to both the limitations and the
      foreseeable impacts of their work. In addition, as members of society, scientists
      have a responsibility to participate in discussions and decisions regarding the
      appropriate use of science in addressing societal issues and concerns, and to
      bring their specialized knowledge and expertise to activities and discussions
      that promote the education of students and fellow citizens, thereby enhancing and
      facilitating informed decision making and democracy. 

PMID- 25574273
TI  - A proposal for considering research integrity from the perspective of behavioral
      economics.

PMID- 25574274
TI  - Life after Misconduct: Promoting Rehabilitation while Minimizing Damage.
AB  - The scientific community has an interest in dealing with misconduct, but also in
      providing a path to rehabilitation in the aftermath of misconduct. The prospect
      of rehabilitation could minimize harms by improving reporting of misconduct,
      rebuilding damaged trust, and providing more insight into the conditions that led
      to unethical behavior, allowing scientists to work collectively to create
      conditions in which scientific misconduct is less likely. 

PMID- 25574275
TI  - Ethical challenges in teaching genetics for medical students.
AB  - Although inclusion of ethics as a study course in medical students' curricula is
      a common practice, special approaches in teaching ethics in the context of
      genetics should be considered. In the realm of genomics, there are several
      ethically sensitive topics such as diagnosis of genetic diseases, in vitro
      fertilization, and identification of genetic susceptibility to common diseases.
      In addition, in communication with the general public, genetic terms should be
      used with caution. Demonstration of the phenotypes of affected individuals should
      be regarded as a particular aspect of teaching genetics. In a description of a
      patient's phenotype, not only is it necessary to provide scientifically precise
      characteristics of a patient; voice timbre, facial expression, and body language
      should also be carefully controlled. Furthermore, in medicine, the theory
      practice gap is a problematic aspect, and students often find it difficult to
      apply knowledge on ethical issues to real situations in clinics. For this
      purpose, clinical cases are presented during classes and their analysis requires
      a very respectful attitude on the part of both students and lecturers. For many
      genetic diseases, evaluation of minor anomalies such as a curved fifth finger,
      low situated ears, or missing of some teeth is required. Some minor anomalies are
      found in healthy individuals too, and interpretation of such features must
      therefore be considered carefully. This article describes our experiences in
      teaching genetics at Riga Stradins University, ethical problems faced while
      teaching genetics, and their solutions. 

PMID- 25574276
TI  - Creating a three-parent child: an educational paradigm for the responsible
      conduct of research.
AB  - The field of assisted reproduction is renowned for its remarkable advances and
      constant pushing forward of research boundaries in an effort to offer innovative
      and effective methods for enhancing fertility. Accompanying these advances,
      however, are physiological, psychological, and bioethical consequences that must
      be considered. These concomitant advances and consequences make assisted
      reproduction an excellent educational paradigm for inculcating responsible
      conduct in both research and clinical practice. Ultimately, responsible conduct
      rests on the ethical researcher and clinician. Here, we present the as-yet
      unapproved, contentious assisted reproductive technology of mitochondrial
      replacement transfer (MRT) as an ideal educational platform to foster the
      responsible conduct of research by advancing dialogue among multi-disciplinary
      scholars, researchers, and students. Using a likely future case, we present the
      basic science, legal, and ethical considerations, and the pedagogical principles
      and strategies for using MRT as an effective educational paradigm. Society will
      benefit when the ethical issues inherent in creating children with three genetic
      parents as well as germline interference are discussed across multiple academic
      levels that include researchers, legal experts, bioethicists, and government
      appointed commissions. Furthermore, undergraduate and graduate students should be
      included because they will likely determine the ethical fates of these
      biotechnologies. While emerging assisted reproduction technologies such as MRT
      are highly complex and will take years to be readily available for patients in
      need, now is the time to consider their scientific, legal, ethical, and
      cultural/religious implications for ensuring the responsible conduct of research.

PMID- 25574277
TI  - Ethical considerations regarding classroom use of personal genomic information.
AB  - Rapidly decreasing costs of genetic technologies-especially next-generation
      sequencing-and intensifying need for a clinical workforce trained in genomic
      medicine have increased interest in having students use personal genomic
      information to motivate and enhance genomics education. Numerous ethical issues
      attend classroom/pedagogical use of students' personal genomic information,
      including their informed decision to participate, pressures to participate,
      privacy concerns, and psychosocial sequelae of learning genomic information. This
      paper addresses these issues, advocates explicit discussion of these issues to
      cultivate students' ethical reasoning skills, suggests ways to mitigate potential
      harms, and recommends collection of ethically relevant data regarding pedagogical
      use of personal genomic information. 

PMID- 25574278
TI  - Personalized genetic testing as a tool for integrating ethics instruction into
      biology courses.
AB  - Personalized genetic testing (PGT) has been used by some educational institutions
      as a pedagogical tool for teaching human genetics. While work has been done that
      examines the potential for PGT to improve students' interest and understanding of
      the science involved in genetic testing, there has been less dialogue about how
      this method might be useful for integrating ethical and societal issues
      surrounding genetic testing into classroom discussions. Citing the importance of
      integrating ethics into the biology classroom, we argue that PGT can be an
      effective educational tool for integrating ethics and science education, and
      discuss relevant ethical considerations for instructors using this approach. 

PMID- 25574279
TI  - Ethics is not rocket science: how to have ethical discussions in your science
      class.

PMID- 25574280
TI  - Cautionary tales: ethics and case studies in science.
AB  - Ethical concerns are normally avoided in science classrooms in spite of the fact
      that many of our discoveries impinge directly on personal and societal values. We
      should not leave the ethical problems for another day, but deal with them using
      realistic case studies that challenge students at their ethical core. In this
      article we illustrate how case studies can be used to teach STEM students
      principles of ethics. 

PMID- 25574281
TI  - Infusing bioethics into biology and microbiology courses and curricula: a
      vertical approach.
AB  - With the rise of biomedicine and biotechnology, there has been a corresponding
      growth in the need for better understanding of consequent ethical questions.
      Increasingly, biologists are being asked not only to offer technical
      clarifications but also to venture ethical opinions, for which most feel poorly
      equipped. This expectation puts pressure on biology instructors at the university
      level to provide biology majors the skills and experience to discuss with some
      confidence and competence bioethical issues which may arise in either the
      workplace or through public discourse in everyday contexts. Many fine curricular
      resources about bioethics are available for varied pedagogical purposes, but few
      target undergraduate biology or microbiology student audiences. When it occurs in
      the context of a course, bioethics instruction often is taught by non-biologists
      outside standard biology curricula. We propose that biologists should strive to
      "infuse" bioethical thinking into their courses and major curricula but not in
      such a way as merely to point at ethical problems, treating them at a surface
      level. We suggest what we call "vertical infusion": taking one bioethical issue
      per course and integrating this issue within the context of a relevant biological
      topic, challenging students to push their thinking beyond their initial
      intuitions toward underlying scientific and ethical principles. While the
      vertical approach lacks widespread coverage of ethical issues throughout a single
      course, it has the advantage of taking the bioethical dimension seriously and in
      intimate relation to contemporary discoveries in biology and to the biological
      principles, processes, or procedures that occasioned the ethical quandaries in
      the first place. 

PMID- 25574282
TI  - Integration of Ethics across the Curriculum: From First Year through Senior
      Seminar.
AB  - The Fisher College of Science and Mathematics (FCSM) at Towson University (TU)
      has integrated authentic research experiences throughout the curriculum from
      first year STEM courses through advanced upper-level classes and independent
      research. Our observation is that training in both responsible conduct of
      research (RCR) and bioethics throughout the curriculum was an effective strategy
      to advance the cognitive and psychosocial development of the students. As
      students enter TU they generally lack the experience and tools to assess their
      own competence, to apply ethical debates, to investigate scientific topics from
      an ethical perspective, or to integrate ethics into final conclusions. Student
      behavior and development follow cognitive models such as described in the
      theories put forth by Piaget, Kohlberg, and Erikson, both for initial learning
      and for how concepts are understood and adopted. Three examples of this ethics
      training integration are described, including a cohort-based course for first
      year students in the STEM Residential Learning Community, a cohort-based course
      for community college students that are involved in an NIH-funded Bridges to the
      Baccalaureate program, and a senior seminar in Bioethics in the Molecular
      Biology, Biochemistry and Bioinformatics Program. All three focus on different
      aspects of RCR and bioethics training, providing opportunities for students to
      learn about the principles of effective decision-making, critical and analytical
      thinking, problem solving, and communication with increasing degrees of
      complexity as they move through the curriculum. 

PMID- 25574283
TI  - Ethical values and biological diversity: a preliminary assessment approach.

PMID- 25574284
TI  - Ethical dilemmas in the biology undergraduate classroom: role-playing
      congressional testimony.
AB  - Students often struggle with weighing multiple sides of bioethical dilemmas. The
      assignment described here incorporates discussion of ethical dilemmas in an upper
      level undergraduate biology course. Students are introduced to ethical dilemmas
      in genetics through discussion of issues in small groups. They are then polled as
      to what positions they take on each dilemma and are assigned to argue a side
      opposite of one of their choices. Each student receives a subpoena to appear
      before a Senate subcommittee to give testimony as an expert witness. This role
      play provides students with a starting point and motivation for developing their
      argument as well as a way to distance themselves from their own opinions by
      acting as someone holding the opposite stance. At the end of the presentations,
      students are required to reflect on the experience. 

PMID- 25574285
TI  - A modern twist on the beaumont and st. Martin case: encouraging analysis and
      discussion in the bioethics classroom with reflective writing and concept
      mapping.
AB  - Historical ethical dilemmas are a valuable tool in bioethics courses. However,
      garnering student interest in reading and discussing the assigned cases in the
      classroom can be challenging. In an effort to actively engage undergraduate and
      graduate students in an Ethical Issues in Biotechnology course, an activity was
      developed to encourage reflection on a classical ethical dilemma between a
      patient, St. Martin, and his employer/caretaker, Beaumont. Two different texts
      were used to analyze the ethical ramifications of this relationship: a chapter in
      a popular press book and a short perspective in a medical journal. Participants
      read the book chapter for homework and discussed it in class. This easy read
      highlights the fundamental ethical issues in the relationship between two men.
      Students were then provided with a second text focusing on the scientific
      accomplishments achieved through Beaumont's experimentation on St. Martin. A
      structured worksheet prompted participants to reflect on their feelings after
      reading each text and create a concept map depicting the dilemma. Student
      generated concept maps and written reflections indicate participants were able to
      list the ethical issues, analyze the situation, and evaluate the information
      provided. This activity not only encouraged higher-level thinking and reflection,
      it also mirrored the course's structured approach of using concept mapping and
      reflection to dissect ethical dilemmas. 

PMID- 25574286
TI  - The tuskegee experiment: an introduction in ethics for pre-healthcare
      professional students.
AB  - Over the past years, professional students have had extensive exposure to
      clinical cases during basic science classes. With this in mind, we have taken
      this clinical case exposure moment to be an opportune time to introduce the
      ethics of working with patients during biomedical research. Our goal is to
      present a straightforward assignment that allows for active student research into
      the facts of the Tuskegee Experiment of the 1900s. The assignment provides the
      necessary background to allow for a student-centered discussion on the ethical
      issues of the events and ramifications of what happened. Thus, in educating a
      class on the event's happenings, one concomitantly creates a platform for
      meaningful discussion on the principles and ethics of patient care. We have found
      that an ethics-infused event such as the Tuskegee Experiment is an excellent way
      to introduce students to these topics. 

PMID- 25574287
TI  - Integrating ethics into case study assignments.
AB  - I teach an upper-level writing course, Genes, Race, Gender, and Society, designed
      for Life Science majors, in which I utilize a case study to expose students to
      ethical ways of thinking. Students first work through the topical case study and
      then are challenged to rethink their responses through the lenses of ethics,
      taking into account different ethical frameworks. Students then develop their own
      case study, integrating ethical components. I want to expose my students to this
      way of thinking because I see technology being driven by the Jurassic Park
      phenomenon, "Your scientists were so preoccupied with whether or not they could,
      they didn't stop to think if they should," and want future physicians grounded in
      a sense of how their actions relate to the greater good. 

PMID- 25574288
TI  - The gen-ethics bowl - an in-class activity combining genetics and bioethics.

PMID- 25574289
TI  - Using a popular science nonfiction book to introduce biomedical research ethics
      in a biology majors course.
AB  - Although bioethics is an important topic in modern society, it is not a required
      part of the curriculum for many biology degree programs in the United States.
      Students in our program are exposed to biologically relevant ethical issues
      informally in many classes, but we do not have a requirement for a separate
      bioethics course. The Immortal Life of Henrietta Lacks is a recent nonfiction
      book that describes the life of the woman whose cervical cancer biopsy gave rise
      to the HeLa cell line, as well as discussing relevant medical, societal, and
      ethical issues surrounding human tissue use for research. Weekly reading
      assignments from the book with discussion questions and a final paper were used
      to engage students in learning about the ethics of human subjects and human
      tissues research. Students were surveyed for qualitative feedback on the
      usefulness of including this book as part of the course. This book has been a
      successful platform for increasing student knowledge and interest in ethics
      related to biomedical and biological research. 

PMID- 25574290
TI  - Topics in bioethics: a development of student perspectives.
AB  - Exposing students to current biotechnological and medical issues is eye-opening
      for many students in a way that is not always achieved through lecture-based
      learning. Lecture or investigative teaching styles provide a tremendous knowledge
      base for the students, but sometimes these teaching styles do not allow the
      student to fully develop, especially personal attitudes to issues in bioethics.
      Through online videos, Hollywood movies, guided readings and classroom
      discussions, students in this course are informed of some bioethical topics,
      encouraged to learn about other topics, and use this gained knowledge to develop
      personal positions regarding the value and/or risk of the issues. This course has
      been well-received by previous students as a favorite in terms of both topics
      covered and style. 

PMID- 25574291
TI  - Correlating student knowledge and confidence using a graded knowledge survey to
      assess student learning in a general microbiology classroom.
AB  - Knowledge surveys are a type of confidence survey in which students rate their
      confidence in their ability to answer questions rather than answering the
      questions. These surveys have been discussed as a tool to evaluate student in
      class or curriculum-wide learning. However, disagreement exists as to whether
      confidence is actually an accurate measure of knowledge. With the concomitant
      goals of assessing content-based learning objectives and addressing this
      disagreement, we present herein a pretest/posttest knowledge survey study that
      demonstrates a significant difference correctness on graded test questions at
      different levels of reported confidence in a multi-semester timeframe. Questions
      were organized into Bloom's taxonomy, allowing for the data collected to further
      provide statistical analyses on strengths and deficits in various levels of
      Bloom's reasoning with regard to mean correctness. Collectively, students showed
      increasing confidence and correctness in all levels of thought but struggled with
      synthesis-level questions. However, when students were only asked to rate
      confidence and not answer the accompanying test questions, they reported
      significantly higher confidence than the control group which was asked to do
      both. This indicates that when students do not attempt to answer questions, they
      have significantly greater confidence in their ability to answer those questions.
      Additionally, when students rate only confidence without answering the question,
      resolution across Bloom's levels of reasoning is lost. Based upon our findings,
      knowledge surveys can be an effective tool for assessment of both breadth and
      depth of knowledge, but may require students to answer questions in addition to
      rating confidence to provide the most accurate data. 

PMID- 25574292
TI  - The development and implementation of an instrument to assess students' data
      analysis skills in molecular biology.
AB  - Developing visual literacy skills is an important component of scientific
      literacy in undergraduate science education. Comprehension, analysis, and
      interpretation are parts of visual literacy that describe related data analysis
      skills important for learning in the biological sciences. The Molecular Biology
      Data Analysis Test (MBDAT) was developed to measure students' data analysis
      skills connected with scientific reasoning when analyzing and interpreting
      scientific data generated from experimental research. The skills analyzed
      included basic skills, such as identification of patterns and trends in data and
      connecting a method that generated the data, and advanced skills, such as
      distinguishing positive and negative controls, synthesizing conclusions,
      determining if data supports a hypothesis, and predicting alternative or next
      step experiments. Construct and content validity were established and calculated
      statistical parameters demonstrate that the MBDAT is valid and reliable for
      measuring students' data analysis skills in molecular and cell biology contexts.
      The instrument also measures students' perceived confidence in their data
      interpretation abilities. As scientific research continues to evolve in
      complexity, interpretation of scientific information in visual formats will
      continue to be an important component of scientific literacy. Thus science
      education will need to support and assess students' development of these skills
      as part of students' scientific training. 

PMID- 25574293
TI  - Positioning genomics in biology education: content mapping of undergraduate
      biology textbooks.
AB  - Biological thought increasingly recognizes the centrality of the genome in
      constituting and regulating processes ranging from cellular systems to ecology
      and evolution. In this paper, we ask whether genomics is similarly positioned as
      a core concept in the instructional sequence for undergraduate biology. Using
      quantitative methods, we analyzed the order in which core biological concepts
      were introduced in textbooks for first-year general and human biology.
      Statistical analysis was performed using self-organizing map algorithms and
      conventional methods to identify clusters of terms and their relative position in
      the books. General biology textbooks for both majors and nonmajors introduced
      genome-related content after text related to cell biology and biological
      chemistry, but before content describing higher-order biological processes.
      However, human biology textbooks most often introduced genomic content near the
      end of the books. These results suggest that genomics is not yet positioned as a
      core concept in commonly used textbooks for first-year biology and raises
      questions about whether such textbooks, or courses based on the outline of these
      textbooks, provide an appropriate foundation for understanding contemporary
      biological science. 

PMID- 25574294
TI  - Hormones and antibiotics in nature: a laboratory module designed to broaden
      undergraduate perspectives on typically human-centered topics.
AB  - Bringing discovery-based research into undergraduate laboratory courses increases
      student motivation and learning gains over traditional exercises that merely
      teach technique or demonstrate well-documented phenomena. Laboratory experiences
      are further enhanced when they are designed to challenge student perspectives on
      topics relevant to their lives. To this end, a laboratory module on antibiotics
      and hormones, which are generally discussed in the context of human health, was
      developed for students to explore the multifaceted roles of antibiotics and
      hormones in nature (e.g. interspecies communication) via reading primary
      scientific literature and performing discovery-based experiments. The main
      objective of this module was to increase the general biological literacy of
      students as determined by their ability to connect the Five Core Concepts of
      Biological Literacy (American Association for the Advancement of Science, Vision
      and Change in Undergraduate Education: A Call to Action, 2011) to the topics
      "hormones" and "antibiotics" in pre- and postmodule surveys. After discussing
      unpublished research findings, cell biology students performed experiments
      demonstrating that: 1) fungi may promote fern growth via hormone production, 2)
      novel bacterial isolates in the genus Streptomyces produce antifungal compounds,
      and 3) subinhibitory antibiotic concentrations may enhance soil bacterial growth.
      The third finding provided evidence supporting a hypothesis framed in a
      scientific article that students read and discussed. Student perspectives on
      premodule surveys focused on roles of hormones and antibiotics in the human body
      (e.g. development, fighting infection), but their broadened postmodule
      perspectives encompassed the roles of these molecules in organismal communication
      and possibly the evolution of multicellularity. 

PMID- 25574295
TI  - Pseudomonas isolation and identification: an introduction to the challenges of
      polyphasic taxonomy.
AB  - The ability to isolate an organism in pure culture from the environment is a
      manageable task for undergraduate students; the identification of that organism
      requires integration of both genotypic and phenotypic data and illustrates the
      challenges inherent in contemporary bacterial taxonomy. In this ten-laboratory
      period series of exercises, students isolate a strain of Pseudomonas from soil
      and characterize its biochemical and physiological properties, as well as
      determine the DNA sequence of its 16S rRNA genes. Integrating these data
      positions students to defend their classification of the isolate as a new species
      or as a member of a validly described species. Assessment data demonstrate that
      both knowledge of and confidence in understanding of the principles of laboratory
      handling of Pseudomonas and bacterial taxonomy increased following the exercises.

PMID- 25574296
TI  - Undergraduate bioinformatics workshops provide perceived skills.

PMID- 25574297
TI  - Styrofoam-and-Velcro: An Alternative to Ball-and-Stick Models.

PMID- 25574298
TI  - Kimchi: spicy science for the undergraduate microbiology laboratory.

PMID- 25574299
TI  - "Pick-up Lines": A Fun Way to Facilitate Learning Microbiological Concepts.

PMID- 25574300
TI  - Using facebook to engage microbiology students outside of class time.

PMID- 25574302
TI  - Build-a-Polypeptide: A Hands-On Worksheet to Enhance Student Learning in an
      Introductory Biology Course.

PMID- 25574301
TI  - From Pipe Cleaners and Pony Beads to Apps and 3D Glasses: Teaching Protein
      Structure.

PMID- 25574303
TI  - Enzymes in action: an interactive activity designed to highlight positive
      attributes of extracellular enzymes synthesized by microbes.

PMID- 25574304
TI  - Experiential posters: theatrical and improvisational tools aid in science museum
      outreach.

PMID- 25574305
TI  - A modified challenge-based learning approach in a capstone course to improve
      student satisfaction and engagement.

PMID- 25574306
TI  - Active learning for basic metabolic pathways.

PMID- 25574307
TI  - An inquiry-based laboratory module to promote understanding of the scientific
      method and bacterial conjugation.

PMID- 25574308
TI  - Inquiry-based laboratory activity to investigate physical growth requirements of
      microorganisms.

PMID- 25574309
TI  - A Multi-Unit Project for Building Scientific Confidence via Authentic Research in
      Identification of Environmental Bacterial Isolates.

PMID- 25574310
TI  - A board game for undergraduate genetics vocabulary and concept review: the
      pathway shuffle.

PMID- 25574311
TI  - Using ASM Podcasts to Excite Undergraduate Students about Current Microbiological
      Research.

PMID- 25574312
TI  - Storytelling as an active learning tool to engage students in a genetics
      classroom.

PMID- 25574314
TI  - [Sturge Weber syndrome associated with glaucoma: report of a case].

PMID- 25574315
TI  - [Cutis marmorata telangiectatica congenita revealing neonatal lupus].

PMID- 25574316
TI  - [Mucinous primitive skin carcinoma: report of two cases and review of the
      literature].

PMID- 25574317
TI  - Unusual case of gastro jejuno-colic fistula with perforation: a rare case report.
AB  - Gastrojejunocolic fistula (GJF) is a late and very rare complication of
      gastroenterostomy performed for recurrent peptic ulcer disease. The occurrence of
      perforation in a GJF is even more a rare complication because long evolution time
      or latent period is required for its appearance. Patients with this condition
      usually present with diarrhea, weight loss, feculent vomiting, under-nutrition
      and features of peritonitis that require immediate surgical intervention.
      Herewith we report a case of 60 year old male with perforation in a
      gastrojejunocolic fistula and its management. 

PMID- 25574318
TI  - An atypical case of intracerebral schwannoma.
AB  - We report a case of intracerebral cystic schwannoma in the temporal fossa
      manifested as a gradually worsening headache in a 49-years-old woman. Computed
      Tomography (CT) and magnetic resonance imaging (MRI) showed a left temporal
      partly cystic, partly solid mass. The preoperative diagnosis was astrocytoma or
      glioblastoma multiforme (GBM), but microscopic examination of the mass showed the
      characteristic pattern with cellular Antony A component. Immunohistochemically,
      the tumor was positive for S-100 protein. These findings are consistent with a
      schwannoma. Intracerebral schwannomas not related to cranial nerves are rare and
      most reported cases involved young patients. 

PMID- 25574319
TI  - [Results of treatment of synovial sarcoma of the limbs].

PMID- 25574320
TI  - A field based evaluation of adverse events following MenAfriVac(r) vaccine
      delivered in a controlled temperature chain (CTC) approach in Benin.
AB  - INTRODUCTION: An estimated one hundred million African meningitis belt residents
      have received MenAfriVac((r))meningococcal serogroup A conjugate vaccine. Since
      October 2012 the vaccine has been licensed for use in a controlled temperature
      chain (CTC) approach, at temperatures of up to 40 degrees C for up to four days.
      The Benin Ministry of Health conducted a pilot evaluation in one of its 34 health
      districts to assess whether the CTC approach was associated with increased
      adverse events following immunisation (AEFIs). METHODES: We compared the
      occurrence of AEFIs during the 5 days following immunisation for 4 villages in
      the district using the CTC approach to 4 villages in another district using the
      traditional approach (vaccine kept at +2 to +8 degrees C). Severe events
      resulting in hospitalisation or death of non-interviewed household members also
      were recorded. RESULTS: We included 1000 persons in the CTC and 999 in the non
      CTC group. Only mild and transient AEFIs were noted in both groups, such as pain
      at injection site or fever. Compared to the non-CTC group, the CTC group had
      similar or lower rates of AEFIs and the occurrence of AEFIs in both groups was
      similar to that indicated in the vaccine package insert. No case of
      hospitalisation or death occurred among interviewed and non-interviewed household
      members. CONCLUSION: The CTC approach, as implemented in Benin, was not
      associated with an increased rate of adverse events in the five days following
      immunisation, either when compared to a concurrent non-CTC population or to
      previous studies.

PMID- 25574321
TI  - PCR pattern of HIV-exposed infants in a tertiary hospital.
AB  - INTRODUCTION: Early infant diagnosis (EID) provides a critical opportunity to
      strengthen follow-up of HIV-exposed children and early access to antiretroviral
      treatment. The study is designed to determine PCR pattern of HIV- exposed
      infants. METHODS: A 2-year cross-sectional study at Usmanu Danfodio University
      Teaching Hospital (UDUTH), Sokoto, Nigeria. All pregnant women that presented to
      our ANC between January, 2011 and December, 2012 were screened for HIV;
      confirmation for seropositivity was from a positive ELISA and then a Western Blot
      assay. PCR was done for all the HIV-exposed babies at 6-8 weeks of age.
      Statistical analysis was done using SPSS version 20.0. RESULTS: Otal delivery was
      6,578. One hundred and sixty three babies from 162 mothers were HIV-exposed; 88
      males, 75 females, with male to female ratio of 1.2:1. Eighty eight (54.0%) of
      the mothers were on HAART before pregnancy; 63 (39.0%) commenced HAART during
      pregnancy while, 12 (7.0%) never received HAART. Three (1.8%) of the HIV-exposed
      babies had a positive PCR. One hundred and thirty nine babies (85.3%) were breast
      fed. CONCLUSION: Mother-to-child-transmission of HIV appears to be on the decline
      in the study area (1.8%), this probably, represents the pattern in other parts of
      the country.

PMID- 25574322
TI  - [Empyema by Nocardia asteroides].

PMID- 25574323
TI  - [Myocardial infarction indicative of essential thrombocythemia in a young black
      African patients: report of a case].

PMID- 25574324
TI  - [Chronic dislocation of the elbow in children: report of 20 cases].

PMID- 25574325
TI  - Capacity indicators for disaster preparedness in hospitals within Nairobi County,
      Kenya.
AB  - The goal of this study was to assess hospital capacity for disaster preparedness
      within Nairobi County. This information would be valuable to institutional
      strategists to resolve weaknesses and reinforce strengths in hospital capacity
      hence ensure efficient and effective service delivery during disasters.
      Analytical cross-sectional research design was used. Indicator variables for
      capacity were hospital equipment, hospital infrastructure, surrounding hospital
      environment, training, drills, staff knowledge and staff capabilities. Thirty two
      hospitals were studied of which nine of them were public hospitals. Data analysis
      was done using SPSS and presented in the form of frequency tables at p < 0.05.
      Study results indicated that hospital capacity to disaster preparedness in
      Nairobi County existed in 22 (68.88%) hospitals, in 6 (64.95%) public hospitals
      and 16 (69.64%) private hospitals. The difference in capacity between public and
      private hospitals within the County was less than 5%. This showed that both
      public and private hospitals were relatively at par, with regard to the capacity
      to handle disaster cases. Study findings also revealed that the surrounding
      hospital environment was the most highly rated indicator while inter hospital
      training and drills were the least rated. Although existent in hospitals within
      Nairobi County, for maximum hospital capacity and disaster preparedness within
      Nairobi County to be achieved, the existent gap in inter hospital training and
      inter hospital drills, both of which fall under the finance health systems
      pillar, required addressing. 

PMID- 25574326
TI  - Risk distribution across multiple health insurance funds in rural Tanzania.
AB  - INTRODUCTION: Multiple insurance funds serving different population groups may
      compromise equity due to differential revenue raising capacity and an unequal
      distribution of high risk members among the funds. This occurs when the funds
      exist without mechanisms in place to promote income and risk cross-subsidisation
      across the funds. This paper analyses whether the risk distribution varies across
      the Community Health Fund (CHF) and National Health Insurance Fund (NHIF) in two
      districts in Tanzania. Specifically we aim to 1) identify risk factors associated
      with increased utilisation of health services and 2) compare the distribution of
      identified risk factors among the CHF, NHIF and non-member households. METHODS:
      Data was collected from a survey of 695 households. A multivariate logisitic
      regression model was used to identify risk factors for increased health care
      utilisation. Chi-square tests were performed to test whether the distribution of
      identified risk factors varied across the CHF, NHIF and non-member households.
      RESULTS: There was a higher concentration of identified risk factors among CHF
      households compared to those of the NHIF. Non-member households have a similar
      wealth status to CHF households, but a lower concentration of identified risk
      factors. CONCLUSION: Mechanisms for broader risk spreading and cross
      subsidisation across the funds are necessary for the promotion of equity. These
      include risk equalisation to adjust for differential risk distribution and
      revenue raising capacity of the funds. Expansion of CHF coverage is equally
      important, by addressing non-financial barriers to CHF enrolment to encourage
      wealthy non-members to join, as well as subsidised membership for the poorest.

PMID- 25574327
TI  - [Giant vertebral hemangioma revealed by lumbar trauma: report of a case].

PMID- 25574328
TI  - Thyroid function in adult Nigerians with metabolic syndrome.
AB  - INTRODUCTION: Metabolic syndrome and thyroid dysfunction are two common disorders
      encountered in the metabolic clinic. Recently, there has been increased interest
      in the association between the two disorders because of the similarities between
      symptoms of hypothyroidism and components of the metabolic syndrome. While some
      reports suggest that metabolic syndrome is associated with subclinical
      hypothyroidism, this concept is largely under investigated in Nigerian adults
      with metabolic syndrome. The aim of this study is to determine the thyroid
      function status of adult Nigerians with metabolic syndrome and determine the
      association, if any, between metabolic syndrome and thyroid function. METHODS:
      This was a cross sectional study of one hundred and fifty adults, members of
      staff of the College of Medicine of the University of Lagos. The participants
      were recruited using a cluster random sampling method. The Ethical Research &
      Review Committee of the institution approved the study protocol and signed
      informed consent was obtained from the participants. The statistics was analysed
      using the IBM SPSS Software of version 19.0. The Student's t test, Chi square
      test and multivariate regression analysis were employed for the analysis.
      Statistical significance was set at p < 0.05. RESULTS: Thirty nine (twenty-six
      percent) of the study participants had metabolic syndrome and one hundred and
      eleven (seventy-four percent) of the study participants did not have metabolic
      syndrome, served as controls. Those who had metabolic syndrome group were
      significantly older (p = 0.03), metabolic syndrome was significantly associated
      with the female gender (p = 0.0002), higher systolic blood pressure (p = 0.0034),
      diastolic blood pressure (p = 0.0009), waist circumference (p < 0.0001), body
      mass index (p < 0.0001), waist-hip ratio (p = 0.003), fasting serum glucose (p =
      0.0457) and free thyroxine (fT4) levels (p = 0.0496). Those with metabolic
      syndrome had significantly lower HDL (P = 0.004) and free triiodothyronine (fT3)
      levels (p = 0.037). There was no statistically significant difference in the
      thyroid stimulating hormone (TSH) levels between individuals with and without
      metabolic syndrome. Thirty-three percent of the metabolic syndrome cases had sick
      euthyroid syndrome (p= < 0.0001). In multivariate regression, waist circumference
      was significantly and inversely associated with the sick euthyroid syndrome (p =
      0.011). CONCLUSION: Metabolic syndrome is associated with the sick euthyroid
      syndrome in adult Nigerians. Abdominal obesity appears to be the link between
      metabolic syndrome and the sick euthyroid syndrome.

PMID- 25574329
TI  - Supernumerary ectopic tooth on the maxillary sinus.

PMID- 25574330
TI  - Severe congenital ocular coloboma.

PMID- 25574332
TI  - [Tiered schwannoma of the median nerve: report of a case].

PMID- 25574331
TI  - Stewart-Treves syndrome: a case report.
AB  - The Stewart-Treves syndrome was first described in 1948, it's an angiosarcoma
      developed on a longstanding lymphadenomatous limb, more often after radical
      mastectomy. Diagnosis is made on skin biopsy and the prognosis is poor when
      radical surgery can't be performed. We report the case on a Stewart-Treves
      syndrome in a sixty-six years old woman who underwent radical mastectomy for
      breast carcinoma ten years earlier. Surgery was not feasible at the time of
      diagnosis, and we lost touch of the patient even if chemotherapy was decided.
      Radical surgery is the best treatment to date for this rare disease. Conservative
      surgery with adjuvant radiotherapy is also possible. Systemic chemotherapy is
      reserved for locally advanced unresectable and metastatic forms. We advocate long
      term follow-up for every post mastectomy lymphedema to diagnosis this fatal
      disease when curable. 

PMID- 25574333
TI  - [Pubalgia of professional athlete: place of surgical treatment, about a
      continuous series of 100 cases].

PMID- 25574334
TI  - [Psychosocial impact of sickle cell disease in the parents of children living in
      Kinshasa, Democratic Republic of Congo: a qualitative study].

PMID- 25574335
TI  - [Interest of the surgical treatment of fractures of the trochanteric mass by
      gamma nail, about 84 cases].

PMID- 25574336
TI  - [Nutritional status of children aged 6 to 59 months with HIV but not on ARVs in
      Lubumbashi].

PMID- 25574338
TI  - William A. Zoghbi, M.D., lends expertise on special imaging issue of The
      Methodist Debakey Cardiovascular Journal.

PMID- 25574339
TI  - Introduction: Cardiovascular imaging in the 21st century.

PMID- 25574337
TI  - Cucurbitacin E has neuroprotective properties and autophagic modulating
      activities on dopaminergic neurons.
AB  - Natural molecules are under intensive study for their potential as preventive
      and/or adjuvant therapies for neurodegenerative disorders such as Parkinson's
      disease (PD). We evaluated the neuroprotective potential of cucurbitacin E (CuE),
      a tetracyclic triterpenoid phytosterol extracted from the Ecballium elaterium
      (Cucurbitaceae), using a known cellular model of PD, NGF-differentiated PC12. In
      our postmitotic experimental paradigm, neuronal cells were treated with the
      parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP(+)) to provoke significant
      cellular damage and apoptosis or with the potent N,N-diethyldithiocarbamate (DDC)
      to induce superoxide (O2(*-)) production, and CuE was administered prior to and
      during the neurotoxic treatment. We measured cellular death and reactive oxygen
      species to evaluate the antioxidant and antiapoptotic properties of CuE. In
      addition, we analyzed cellular macroautophagy, a bulk degradation process
      involving the lysosomal pathway. CuE showed neuroprotective effects on MPP(+)
      induced cell death. However, CuE failed to rescue neuronal cells from oxidative
      stress induced by MPP(+) or DDC. Microscopy and western blot data show an
      intriguing involvement of CuE in maintaining lysosomal distribution and
      decreasing autophagy flux. Altogether, these data indicate that CuE decreases
      neuronal death and autophagic flux in a postmitotic cellular model of PD.

PMID- 25574340
TI  - Cardiovascular imaging: a glimpse into the future.
AB  - In a relatively short span, technological developments in cardiovascular imaging
      have infiltrated every aspect of practice, with noticeable improvements in
      diagnosis and impact on patient management. All imaging technologies have
      undergone continual improvements since their inception to a point that imaging
      has become essential in both clinical practice and research. This article
      provides a glimpse into the future of cardiovascular imaging and highlights areas
      of imaging that still need improvement, with a view towards improving the
      practice of health care, where efficiency and value are becoming ever more
      dominant criteria throughout the continuum of care. 

PMID- 25574341
TI  - Important advances in technology: echocardiography.
AB  - Echocardiography has evolved over the past 45 years from a simple M-mode tracing
      to an array of technologies that include two-dimensional imaging, pulsed and
      continuous wave spectral Doppler, color flow and tissue Doppler, and
      transesophageal echocardiography. Together, these modalities provide a
      comprehensive anatomic and functional evaluation of cardiac chambers and valves,
      pericardium, and ascending and descending aorta. The switch from analog to
      digital signal processing revolutionized the field of ultrasound, resulting in
      improved image resolution, smaller instrumentation that allows bedside evaluation
      and diagnosis of patients, and digital image storage for more accurate
      quantification and comparison with previous studies. It also opened the door for
      new advances such as harmonic imaging, automated border detection and
      quantification, 3-dimensional imaging, and speckle tracking. This article offers
      an overview of some newer developments in echocardiography and their promising
      applications. 

PMID- 25574342
TI  - Important advances in technology and unique applications to cardiovascular
      computed tomography.
AB  - For the past decade, multidetector cardiac computed tomography and its main
      application, coronary computed tomography angiography, have been established as a
      noninvasive technique for anatomical assessment of coronary arteries. This new
      era of coronary artery evaluation by coronary computed tomography angiography has
      arisen from the rapid advancement in computed tomography technology, which has
      led to massive diagnostic and prognostic clinical studies in various patient
      populations. This article gives a brief overview of current multidetector cardiac
      computed tomography systems, developing cardiac computed tomography technologies
      in both hardware and software fields, innovative radiation exposure reduction
      measures, multidetector cardiac computed tomography functional studies, and their
      newer clinical applications beyond coronary computed tomography angiography. 

PMID- 25574343
TI  - Important advances in technology and unique applications related to cardiac
      magnetic resonance imaging.
AB  - Cardiac magnetic resonance has become a well-established imaging modality and is
      considered the gold standard for myocardial tissue viability assessment and
      ventricular volumes quantification. Recent technological hardware and software
      advancements in magnetic resonance imaging technology have allowed the
      development of new methods that can improve clinical cardiovascular diagnosis and
      prognosis. The advent of a new generation of higher magnetic field scanners can
      be beneficial to various clinical applications. Also, the development of faster
      acquisition techniques have allowed mapping of the magnetic relaxation properties
      T1, T2, and T2* in the myocardium that can be used to quantify myocardial diffuse
      fibrosis, determine the presence of edema or inflammation, and measure iron
      within the myocardium, respectively. Another recent major advancement in CMR has
      been the introduction of three-dimension (3D) phase contrast imaging, also known
      as 4D flow. The following review discusses key advances in cardiac magnetic
      resonance technology and their potential to improve clinical cardiovascular
      diagnosis and outcomes. 

PMID- 25574344
TI  - Nuclear cardiology: 2014 innovations and developments.
AB  - Nuclear cardiac imaging is acknowledged as a robust technique for clinically
      assessing patients with a wide spectrum of cardiac illnesses. Recent technical,
      radiotracer, and stressor advancements continue to expand the role of nuclear
      cardiology for the accurate diagnosis and prognostication of patients with known
      or suspected coronary artery disease. The introduction of I-123 MIBG represents
      another advance for assessing risk in patients with congestive heart failure and
      depressed left ventricular (LV) function. Software and hardware innovations and
      recent shifts in acquisition protocols have greatly improved image quality,
      reduced cost and radiation exposure, and continue to promote patient and
      physician satisfaction. The following article will highlight recent achievements
      in the field that continue to foster a patient-centered imaging approach. 

PMID- 25574346
TI  - Overview of quality in cardiovascular imaging and procedures for clinicians:
      focus on appropriate-use-criteria guidelines.
AB  - Cardiovascular imaging and procedures have experienced exponential growth over
      the past 20 years in terms of new modalities, procedure volume, technological
      sophistication, and cost. As a result, related quality improvement tools have
      become multifaceted works in progress. This article briefly summarizes the
      evolution of the time-honored American College of Cardiology Foundation/American
      Heart Association clinical practice guidelines versus the newer American College
      of Cardiology Foundation appropriate-use-criteria guidelines and how these may
      interact with emerging performance measures, clinical data registries, and
      cardiovascular laboratory accreditation initiatives. 

PMID- 25574345
TI  - Interventional imaging: the role of echocardiography.
AB  - Interventional echocardiography is a rapidly evolving field requiring imaging
      expertise. An increasing number of structural heart interventions now require
      real-time imaging guidance for device placement and immediate functional
      evaluation. Continuous 2- and 3-dimensional transesophageal echocardiography are
      now required by many heart teams during complex structural interventions,
      including percutaneous closure of atrial septal defects, left atrial appendage
      occlusion, transcatheter aortic valve replacement (TAVR), transcatheter repair of
      paravalvular regurgitation, and percutaneous mitral valve repair. In this review,
      we describe the role of echocardiography during the initial structural
      evaluation, throughout the device placement procedure, and for the assessment of
      acute device function and complications. 

PMID- 25574347
TI  - Review of recent results using computational fluid dynamics simulations in
      patients receiving mechanical assist devices for end-stage heart failure.
AB  - Many end-stage heart failure patients are not eligible to undergo heart
      transplantation due to organ shortage, and even those under consideration for
      transplantation might suffer long waiting periods. A better understanding of the
      hemodynamic impact of left ventricular assist devices (LVAD) on the
      cardiovascular system is therefore of great interest. Computational fluid
      dynamics (CFD) simulations give the opportunity to study the hemodynamics in this
      patient population using clinical imaging data such as computed tomographic
      angiography. This article reviews a recent study series involving patients with
      pulsatile and constant-flow LVAD devices in which CFD simulations were used to
      qualitatively and quantitatively assess blood flow dynamics in the thoracic
      aorta, demonstrating its potential to enhance the information available from
      medical imaging. 

PMID- 25574348
TI  - Case report: Bilateral renal artery stenosis in a 7-year-old child.
AB  - We present a 7-year-old child with uncontrolled hypertension caused by bilateral
      renal artery stenosis. He underwent renal angioplasty on both sides. While the
      right side showed successful dilatation, the left side was unsuccessful, leaving
      a near total occlusion. Due to the lack of satisfactory control of his blood
      pressure, he was scheduled for an iliorenal bypass. Following surgery, all
      antihypertensive medications were withdrawn. Computed tomography angiography
      performed 18 months after surgery showed patent angioplasty on the right side and
      patent bypass on the left side. Both endovascular and open surgical treatments
      are feasible options with good results in this age group. 

PMID- 25574350
TI  - Case report: It wasn't cupid: multimodality imaging of inferior vena cava filter
      fracture with strut migration to the interventricular septum.

PMID- 25574351
TI  - Museum image: Anomalous left circumflex artery coexisting with atrial septal
      defect.

PMID- 25574349
TI  - Case report: Severe hypercalcemia mimicking ST-segment elevation myocardial
      infarction.
AB  - The identification of ST-segment elevation on the electrocardiogram is an
      integral part of decision making in patients who present with suspected ischemia.
      Unfortunately, ST-segment elevation is nonspecific and may be caused by
      noncardiac causes such as electrolyte abnormalities. We present a case of ST
      segment elevation secondary to hypercalcemia in a patient with metastatic cancer.

PMID- 25574352
TI  - Points to remember: Cardiovascular consequences of hemodialysis vascular
      accesses.

PMID- 25574353
TI  - Editorial: Wading the river.

PMID- 25574355
TI  - Dr. Phil's art corner: Valkyrie sky concord and got him on the run.

PMID- 25574356
TI  - Essay on being a doctor: Worth following.

PMID- 25574358
TI  - EDL-360: A Potential Novel Antiglioma Agent.
AB  - Glioma is a brain tumor that arises from glial cells or glial progenitor cells,
      and represents 80% of malignant brain tumor incidence in the United States.
      Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor
      malignancy with fewer than 8% of patients with GBM surviving for more than 3
      years. Over the past 10 years, despite improvement in diagnosis and therapies for
      cancer, the survival rate for high-grade glioma patients remains dismal. The main
      focus of our research is to identify potent novel antiglioma small molecules. We
      previously showed that EDL-360, a tetrahydroisoquinoline (THIQ) analog, as being
      highly cytotoxic to human glioma cell cultures. Here we show that EDL-360
      significantly induced apoptosis in human glioma cell lines (U87 and LN18).
      However, in normal astrocytic cells, EDL-360 induced a modest G0/G1 cell cycle
      arrest but did not induce apoptosis. In an attempt to enhance EDL-360 induced
      cell death, we tested simultaneous treatment with EDL-360 and embelin (an
      inhibitor of the anti-apoptotic protein, XIAP). We found that, glioma cells had
      significant lower viability when EDL-360 and embelin were used in combination
      when compared to EDL-360 alone. We also used combination treatment of EDL-360
      with decylubiquinone (dUb), a caspase-9 inhibitor, and found that the combination
      treatment induced a significant cell death when compared to treatment with EDL
      360 alone. This is the first report that suggests that dUb has anticancer
      activity, and perhaps acts as a XIAP inhibitor. Finally, our in vivo data showed
      that EDL-360 treatment induced a partial regression in glioma tumorigenesis and
      induced cell death in the treated tumors as shown by H&E staining. Taken together
      these data suggests that EDL-360 has a potential therapeutic application for
      treating glioma, especially when combined with XIAP inhibitors.

PMID- 25574359
TI  - Building Service Delivery Networks: Partnership Evolution Among Children's
      Behavioral Health Agencies in Response to New Funding.
AB  - Meeting the complex needs of youth with behavioral health problems requires a
      coordinated network of community-based agencies. Although fiscal scarcity or
      retrenchment can limit coordinated services, munificence can stimulate service
      delivery partnerships as agencies expand programs, hire staff, and spend more
      time coordinating services. This study examines the 2-year evolution of referral
      and staff expertise sharing networks in response to substantial new funding for
      services within a regional network of children's mental health organizations.
      Quantitative network survey data were collected from directors of 22 nonprofit
      organizations that receive funding from a county government-based behavioral
      health service fund. Both referral and staff expertise sharing networks changed
      over time, but results of a stochastic actor-oriented model of network dynamics
      suggest the nature of this change varies for these networks. Agencies with higher
      numbers of referral and staff expertise sharing partners tend to maintain these
      ties and/or develop new relationships over the 2 years. Agencies tend to refer to
      agencies they trust, but trust was not associated with staff expertise sharing
      ties. However, agencies maintain or form staff expertise sharing ties with
      referral partners, or with organizations that provide similar services. In
      addition, agencies tend to reciprocate staff expertise sharing, but not
      referrals. Findings suggest that during periods of resource munificence and
      service expansion, behavioral health organizations build service delivery
      partnerships in complex ways that build upon prior collaborative history and
      coordinate services among similar types of providers. Referral partnerships can
      pave the way for future information sharing relationships.

PMID- 25574360
TI  - Modern immunotherapy of adult B-lineage acute lymphoblastic leukemia with
      monoclonal antibodies and chimeric antigen receptor modified T cells.
AB  - The introduction of newer cytotoxic monoclonal antibodies and chimeric antigen
      receptor modified T cells is opening a new age in the management of B-lineage
      adult acute lymphoblastic leukemia. This therapeutic change must be very
      positively acknowledged because of the limits of intensive chemotherapy programs
      and allogeneic stem cell transplantation. In fact, with these traditional
      therapeutic tools the cure can be achieved in only 40-50% of the patients. The
      failure rates are particularly high in the elderly, in patients with post
      induction persistence of minimal residual disease and especially in
      refractory/relapsed disease. The place of the novel immunotherapeutics in
      improving the outcome of adult patients with B-lineage acute lymphoblastic
      leukemia is reviewed. 

PMID- 25574361
TI  - Diagnostic value of bronchoalveolar lavage in leukemic and bone marrow transplant
      patients: the impact of antimicrobial therapy.
AB  - There is significant morbidity and mortality from pneumonia in leukemic and bone
      marrow transplant patients. We sought to explore the diagnostic yield of
      bronchoalveolar lavage (BAL) in these patients with new pulmonary infiltrates. A
      retrospective chart review of approximately 200 Non- human immunodeficiency virus
      (HIV) leukemic and Hematopoietic stem cell transplantation (HSCT) patients who
      underwent bronchoscopy at a single academic cancer center was performed.
      Antimicrobial use for less than 24 hours at the time of BAL was associated with a
      higher yield in this population (56.8% versus 32.8%, p<0.001). This supports
      performing bronchoscopy with BAL within 24 hours of antimicrobial therapy in
      leukemic and HSCT patients. 

PMID- 25574362
TI  - Occurrence of secondary malignancies in chronic myeloid leukemia during therapy
      with imatinib mesylate-single institution experience.
AB  - INTRODUCTION: Imatinib mesylate (IM) remains the treatment of choice for chronic
      myeloid leukemia (CML) showing a remarkable efficacy and offers a perspective for
      long disease-free survival. Due to prolonged administration of IM, the questions
      about the possible impact on the development of secondary malignancies (SM) are
      raised. OBJECTIVE: To investigate the incidence and clinical outcome of secondary
      malignancies during IM therapy for CML. MATERIAL AND METHODS: The records of 221
      CML patients treated with IM between 2003-2013 in a single institution were
      reviewed. The Poisson regression model was used to estimate the relative risks
      for SM and death in CML patients. RESULTS: Secondary malignancies developed in
      eight out of the 221 patients (3.6%) receiving IM for a median of 61 months
      (range, 10-137 months). Female/male ratio was 5/3. Two patients were diagnosed
      with their CML at accelerated phase whereas 6 had chronic phase. The median age
      at IM initiation was 58 years (range, 31-72 years). Five of these 8 SM patients
      received IM after other treatments failure: interferon alpha (n=5), hydroxyurea
      (n=4) and cytarabine (n=1). Three patients received IM as a frontline therapy.
      All patients were on IM at 400mg daily at SM occurrence. The therapy for SM
      included surgery (n=3), chemotherapy only (n=3), and chemotherapy followed by
      radiotherapy (n=1). One patient did not receive treatment due to disseminated
      disease. All CML patients were in hematologic and complete cytogenetic response
      (CCR) at the time of SM development. All of them also met the criteria for major
      molecular response (BCR-ABL(IS) <=0.1%). They continued their IM while receiving
      treatment for SM. Among eight patients with SM, five patients are alive and
      remain in CCR on IM whereas three patients died due to SM. The risks for SM
      development as well as death due to SM in CML patients were not statistically
      increased if compared to age-adjusted population. CONCLUSIONS: The association
      between IM therapy for CML and SM development has not been found.

PMID- 25574363
TI  - Prevalence of alpha thalassemia in microcytic anemia: a tertiary care experience
      from north India.
AB  - INTRODUCTION: Cases with microcytosis not responding adequately to iron
      supplementation are diagnostic dilemma and have been reported to harbor alpha
      (alpha) thalassemia mutations. The aim of this study was to determine the common
      alpha globin gene deletions in cases with microcytic anemia. METHODS: Fifty four
      patients selected (22 females and 32 males) had microcytic anemia (MCV < 80 fl,
      Hb <12gm/dl) with raised TRBC (> 5M/mm3) but normal Hb HPLC. They had either low
      or normal Transferrin Saturation (TS). Gap-PCR for four common alpha-gene
      deletions (-alpha(3.7), -alpha(4.2), - -alpha(SA) and --alpha(SEA)) was done.
      RESULTS: Out of the total fifty-four cases nineteen (35.2%) cases were found to
      have alpha gene mutations; Three homozygous and sixteen heterozygous cases
      including -alpha(3.7) deletions and a single case of -- alpha (SA) ; but no 
      alpha(4.2) and -(SEA) mutations were found. CONCLUSION: alpha gene mutations can
      confound iron deficiency anemia, but no RBC indices, or a discriminant function
      can identify it is presence Molecular studies have to be resorted to. Gap PCR for
      common alpha thalassemia mutation including -alpha (SA) should be done even in
      the face of low iron stores in subjects who respond incompletely to iron
      supplementation.

PMID- 25574365
TI  - Invasive pulmonary aspergillosis in a haematopoietic stem cell transplant
      recipient with sickle cell disease: a successful treatment.
AB  - Sickle Cell Anaemia (SCA) is the most common inherited blood disorder and is
      associated with severe morbidity and decreased survival. Allogeneic
      Haematopoietic Stem Cell Transplantation (HSCT) is the only curative approach.
      Nevertheless the decision to perform a bone marrow transplant includes the risk
      of major complications and transplant-related mortality. Infections represent the
      leading cause of death in SCA patients undergoing HSCT. Invasive Pulmonary
      Aspergillosis (IPA) is a devastating opportunistic infection and remains a
      significant cause of morbidity and mortality in HSCT recipients. Data regarding
      IPA in the setting of SCA are lacking. In the present report, we describe a
      patient with SCA, who developed IPA after allogeneic bone marrow transplant. The
      fungal infection was treated by systemic antifungal therapy in addition to
      surgery, despite mild chronic graft versus host disease (GVHD) and continuing
      immunosuppressive therapy. This case shows that IPA occurring in bone marrow
      recipients with SCA can be successfully treated. 

PMID- 25574364
TI  - The Frequency of Adrenal Insufficiency in Adolescents and Young Adults with
      Thalassemia Major versus Thalassemia Intermedia in Iran.
AB  - BACKGROUND: Endocrine dysfunction is not uncommon complication in patients with
      transfusion-dependent thalassemia and is thought to occur as a consequence of
      excessive iron overload. The primary objective of this study is to determine the
      frequency of adrenal insufficiency in patients with thalassemia major and
      thalassemia intermediate. METHODS: This cross-sectional study was done at the
      Shiraz University of Medical Sciences, Shiraz, Southern Iran, in 2013. One
      hundred and ninety patients were divided into two groups; thalassemia major(TM)
      and thalassemia intermediate (TI) groups. We measured 8 AM serum cortisol, ACTH
      and ferritin concentrations in all patients. RESULTS: The mean age of the TM and
      TI group were 22.5+/-5.7 and 23.8+/-6 years, respectively. 90 patients (47.4%)
      were splenectomized, 34 (36.2%) with TM and 56 (58.2%) with TI (p :<0.001). The
      median and interquartile range of serum ferritin levels were 2184+/-3700 ng/ml
      and 437+/-443ng/ml in TM and TI respectively (p< 0.001). Three patients with TM
      (1.6%) had low basal cortisol and ACTH levels. However, their cortisol response
      to ACTH stimulation was normal. CONCLUSIONS: Low basal concentrations of cortisol
      and ACTH occurred in 1.6% of our adolescents young adult patients with TM
      suggesting a central defect in cortisol secretion at the basal state. However,
      cortisol response to standard - dose ACTH was normal in all patients with TM and
      TI.

PMID- 25574366
TI  - Postpandemic Influenza A/H1N1pdm09 is still Causing Severe Perinatal
      Complications.
AB  - Although influenza A/H1N1pdm09 is not causing a pandemic anymore, we recently
      observed two critically ill pregnant women infected by this virus. We present
      these cases to illustrate the possible severe complications of an - at that
      moment - seasonal influenza in pregnancy. We discuss the epidemiological
      differences between the pandemic and post pandemic phase and try to explain the
      high virulence of influenza A/H1N1pdm09 -infections in pregnancy by discussing
      insights in immunology during pregnancy. We conclude that although influenza
      A/H1N1pdm09 is in the post pandemic phase, infection by this influenza virus
      still needs to be considered in pregnant women with progressive respiratory
      dysfunction. 

PMID- 25574368
TI  - Prognostic Impact of Neuropilin-1 Expression in Egyptian Children with B-lineage
      Acute Lymphoblastic Leukemia.
AB  - BACKGROUND: Neuropilins are transmembrane glycoproteins that act as receptors for
      vascular endothelial growth factors and are involved in the process of tumor
      angiogenesis. OBJECTIVE: The aim of this work was to study the prognostic value
      of Neuropilin-1 (NRP-1) expression in Egyptian children with B-lineage acute
      lymphoblastic leukemia (ALL). PATIENTS AND METHODS: This study was conducted on
      fifty children with newly diagnosed B-lineage ALL, admitted to Oncology Unit,
      Pediatric Department, Tanta University Hospitals in the period from August 2010
      to March 2014. This series included 32 males and 18 females with ages ranging
      from 3-17 years and a mean value of 9 +/- 3.5 years. Twenty healthy children, age
      and sex matched, were also included in this study as a control group. For all
      patients, the following examens were done: Bone marrow aspiration, cytochemistry,
      immunophenotyping and estimation of Neuropilin-1 expression on blast cells by
      flow cytometry. RESULTS: The present study revealed highly significant
      differences in Neuropilin-1 expression between B-lineage ALL lymphoblasts and
      control lymphocytes. A significant higher Neuropilin-1 expression was found in
      pre-B ALL (74.04%) compared with early pre-B (23.55%). Neuropilin-1 positive
      expression was associated with significantly higher white blood cells count (Mean
      = 69.3+/-18.53 *10(3)/mm(3) versus 32.5+/-11.64 *10(3)/mm(3) and p=0.003), bone
      marrow blasts percentage (Mean=76.12+/-21.4 % versus 41.2+/-19.71% and p= 0.003),
      serum lactate dehydrogenase levels (Mean=1992.2 +/- 58.6 unit/L versus 955.1+/-
      234.7 unit/L and p=0.001) at diagnosis compared with negative Neuropilin-1
      expression. The levels of Neuropilin-1 on BM blasts at diagnosis were higher in
      patients who subsequently relapsed (Mean=53.8 +/- 27.1) or later died (Mean=81.51
      +/- 9.94) during the period of follow-up compared to those who achieved and
      maintained complete remission (Mean=18.17 +/- 10.4) with p value of 0.001.
      Furthermore, patients with higher Neuropilin-1 expression had significantly
      shorter overall survival (Median 27.99 months and p= 0.0133) and disease-free
      survival (Median=10.23 months and p= 0.0002) than patients with low Neuropilin-1
      expression (Median disease-free survival was 38.7 months). CONCLUSION: Our
      findings suggest that Neuropilin-1 is a poor prognosis factor in children with B
      lineage ALL and so we recommend the inclusion of Neuropilin-1 as a prognostic
      marker in children with B-lineage ALL. Its presence at high levels suggests a
      poor prognosis, and the necessity of intensive therapeutic intervention.

PMID- 25574367
TI  - Hemophagocytic Lymphohistiocytosis: an Unusual Complication of Orientia
      tsutsugamushi Disease (Scrub Typhus).
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially
      fatal, hyperinflammatory syndrome that may rarely complicate the clinical course
      of Orientia tsutsugamushi disease (scrub typhus). METHODS: Here we describe the
      clinicopathological features, laboratory parameters, management, and outcome of
      three adult patients (1 female, 2 males) with scrub typhus associated HLH from a
      tertiary center. A brief and concise review of international literature on the
      topic was also added. RESULTS: All three patients satisfied the HLH-2004
      diagnostic criteria; one had multi-organ dysfunction with very high ferritin
      level (>30,000 ng/ml), and all had a dramatic recovery following doxycyclin
      therapy. Literature review from January 1990 to March 2014 revealed that scrub
      typhus associated HLH were reported in 21 patients, mostly from the scrub endemic
      countries of the world. These included 11 females and 10 males with a mean age of
      35 years (range; 8 months to 81 years). Fifteen of 17 patients (where data were
      available) had a favorable outcome following early serological diagnosis and
      initiation of definitive antibiotic therapy with (N=6) or without (N=9)
      immunosuppressive/immunomodulator therapy. Mutation analysis for primary HLH was
      performed in one patient only, and HLH-2004 protocol was used in two patients.
      CONCLUSION: We suggest that HLH should be considered in severe cases of scrub
      typhus especially if associated with cytopenia (s), liver dysfunction, and
      coagulation abnormalities. Further studies are required to understand whether an
      immunosuppressive and/or immunomodulator therapy could be beneficial in those
      patients who remain unresponsive to definitive antibiotic therapy.

PMID- 25574369
TI  - NF-kappaB Essential Modulator Deficiency Leading to Disseminated Cutaneous
      Atypical Mycobacteria.
AB  - NF-kappaB essential modulator (NEMO) is a kinase integral to the macrophage TNF
      alpha pathway, which leads to the intracellular destruction of Mycobacteria
      species. Defects in the NEMO pathway result in spectrum of diseases, including
      but not limited to ectodermal dysplasia, Mendelian susceptibility to
      mycobacterial diseases, and incontinentia pigmenti. In addition, paucity of NEMO
      can lead to the inability to mount a proper immune response against opportunistic
      pyogenic and mycobacterial infections, leading to dissemination to various organ
      systems. This manuscript will discuss the numerous clinical manifestations of
      NEMO deficiency, the differential diagnosis of atypical mycobacterial infections
      in immunocompetent adults, and feature a case report of rare isolated
      susceptibility to disseminated atypical mycobacteria due to a mutation in the
      first exon of the NEMO gene. 

PMID- 25574370
TI  - Brain Abscesses Caused by Nocardia paucivorans in a Multiple Myeloma Patient
      Treated with Lenalidomide and Dexamethasone: a Case Report and Review of
      Literature.
AB  - We report the first case of multiple brain abscesses caused by Nocardia
      paucivorans in a patient suffering from multiple myeloma on treatment with
      lenalidomide and dexamethasone. N. paucivorans is a recently described species of
      the genus Nocardia, which is supposed to have a heightened neurotropism in cases
      of disseminated infection. Although nocardiosis itself is an uncommon infectious
      complication in multiple myeloma so far, nocardial brain abscess should be added
      to the spectrum of adverse effects due to this novel chemotherapy regimen. 

PMID- 25574371
TI  - A Multicenter Experience from Lebanon in Childhood and Adolescent Acute Myeloid
      Leukemia: High rate of Early Death in Childhood Acute Promyelocytic Leukemia.
AB  - BACKGROUND: Acute myeloid leukemia (AML) is a disease with marked heterogeneity.
      Despite major improvement in outcome, it remains a life-threatening malignancy.
      Demographic and clinical data on pediatric AML is lacking among the Lebanese
      population. PURPOSE: We aimed to identify clinical, molecular and outcome data in
      children with AML in Lebanon. METHODS: A retrospective chart review of children
      with AML diagnosed in three Lebanese hospitals during the past 8 years was
      conducted. RESULTS: From May 2002 through March 2010, we identified 24 children
      with AML in Saint George Hospital University Medical Center, University Medical
      Center Rizk Hospital, and Abou-Jaoude Hospital. Males and females were equally
      represented; median age at diagnosis was 9 years (range 1-24) and median WBC at
      diagnosis was 31 * 10(9)/L (range: 2.1-376 * 10(9)/L). Twenty five percent of
      patients (6 out of 24) had acute promyelocytic leukemia (APL). Karyotype was
      normal in 33% of patients; t(8;21), inv (16), t(8;9), t(7;11), t(9;11), complex
      chromosomal abnormality, monosomy 7 and trisomy 8 were the most common
      cytogenetic abnormalities encountered. Patients were treated on different
      European and North American protocols. Twelve patients (50%) achieved morphologic
      CR after cycle 1, 6 of them (50%) had bone marrow relapse within 11 months from
      diagnosis. Nine patients underwent allogeneic stem cell transplant, and 3 of them
      are alive at 5 years post-transplant. Early death rate was 16.6% of patients,
      mainly those with APL and a presenting WBC > 10 * 10(9)/L. Fifty per cent of APL
      patients had an early death due to DIC despite starting ATRA therapy. Overall,
      median survival for AML patients who died from disease progression was 25.8
      months (range: 1-60 months). Overall disease-free survival was 30.4%. Patients <
      10 years of age had a 50% survival rate compared to 0% in patients > 10 years.
      CONCLUSIONS: Our report highlights the needs in Lebanon for better supportive
      care of children with APL, including faster ATRA administration and, aggressive
      transfusions, easy access to stem cell transplant for high-risk AML patients and
      the need for a national homogenous treatment strategy for children with AML.

PMID- 25574372
TI  - New chemical probes targeting cholesterylation of Sonic Hedgehog in human cells
      and zebrafish.
AB  - Sonic Hedgehog protein (Shh) is a morphogen molecule important in embryonic
      development and in the progression of many cancer types in which it is aberrantly
      overexpressed. Fully mature Shh requires attachment of cholesterol and palmitic
      acid to its C- and N-termini, respectively. The study of lipidated Shh has been
      challenging due to the limited array of tools available, and the roles of these
      posttranslational modifications are poorly understood. Herein, we describe the
      development and validation of optimised alkynyl sterol probes that efficiently
      tag Shh cholesterylation and enable its visualisation and analysis through
      bioorthogonal ligation to reporters. An optimised probe was shown to be an
      excellent cholesterol biomimetic in the context of Shh, enabling appropriate
      release of tagged Shh from signalling cells, formation of multimeric transport
      complexes and signalling. We have used this probe to determine the size of
      transport complexes of lipidated Shh in culture medium and expression levels of
      endogenous lipidated Shh in pancreatic ductal adenocarcinoma cell lines through
      quantitative chemical proteomics, as well as direct visualisation of the probe by
      fluorescence microscopy and detection of cholesterylated Hedgehog protein in
      developing zebrafish embryos. These sterol probes provide a set of novel and well
      validated tools that can be used to investigate the role of lipidation on
      activity of Shh, and potentially other members of the Hedgehog protein family.

PMID- 25574373
TI  - An evaluation of recruitment methods utilized for a clinical trial with
      periodontal and diabetes enrollment criteria: the Diabetes and Periodontal
      Therapy Trial.
AB  - BACKGROUND: Diabetes and its complications are a major United States public
      health concern. METHODS: The Diabetes and Periodontal Therapy Trial (DPTT)
      evaluated whether non-surgical treatment of periodontal disease influenced
      diabetes management among persons with Type 2 diabetes and periodontitis. The aim
      of this study was to evaluate DPTT's many recruitment strategies in terms of
      enrollment success. RESULTS/CONCLUSION: Targeted recruitment strategies were more
      effective in identifying individuals who met periodontal and diabetes eligibility
      criteria. Individuals eligible for a baseline visit/enrollment were more often
      male, had a younger age at diabetes diagnosis, a longer diabetes duration, more
      often Hispanic and less often African-American. Tracking and evaluating
      recruitment sources during study enrollment optimized recruitment methods to
      enroll a diverse participant population based upon gender, race and ethnicity.

PMID- 25566350
TI  - Case Report: Mammary and rectal metastases from an ovarian cancer: report of two
      cases and review of literature.
AB  - In this paper we report two interesting cases of metastatic ovarian cancer. The
      first case is a patient who developed rectal and breast metastases mimicking an
      inflammatory breast cancer. In the second case, subclinical breast and axillary
      lymph node metastases were revealed by PET/CT. Metastases in the breast
      originating from solid tumors are extremely rare. The ovarian primitive is the
      fourth most common origin. The occurrence of breast metastasis is associated with
      an advanced disease and a poor prognosis. Their incidence is increasing since
      they are found more often due to better imaging techniques and to better
      treatment that, accordingly, improve patients' survival. Thus, unusual sites of
      metastases are more and more reported. Indeed, some authors reported the
      occurrence of colorectal metastases from ovarian cancer. However, they remain
      much less frequent. 

PMID- 25566351
TI  - Discovery of functional non-coding conserved regions in the alpha-synuclein gene
      locus.
AB  - Several single nucleotide polymorphisms (SNPs) and the Rep-1 microsatellite
      marker of the alpha-synuclein ( SNCA) gene have consistently been shown to be
      associated with Parkinson's disease, but the functional relevance is unclear.
      Based on these findings we hypothesized that conserved cis-regulatory elements in
      the SNCA genomic region regulate expression of SNCA, and that SNPs in these
      regions could be functionally modulating the expression of SNCA, thus
      contributing to neuronal demise and predisposing to Parkinson's disease. In a
      pair-wise comparison of a 206kb genomic region encompassing the SNCA gene, we
      revealed 34 evolutionary conserved DNA sequences between human and mouse. All
      elements were cloned into reporter vectors and assessed for expression modulation
      in dual luciferase reporter assays.  We found that 12 out of 34 elements
      exhibited either an enhancement or reduction of the expression of the reporter
      gene. Three elements upstream of the SNCA gene displayed an approximately 1.5
      fold (p<0.009) increase in expression. Of the intronic regions, three showed a
      1.5 fold increase and two others indicated a 2 and 2.5 fold increase in
      expression (p<0.002). Three elements downstream of the SNCA gene showed 1.5 fold
      and 2.5 fold increase (p<0.0009). One element downstream of SNCA had a reduced
      expression of the reporter gene of 0.35 fold (p<0.0009) of normal activity. Our
      results demonstrate that the SNCA gene contains cis-regulatory regions that might
      regulate the transcription and expression of SNCA. Further studies in disease
      relevant tissue types will be important to understand the functional impact of
      regulatory regions and specific Parkinson's disease-associated SNPs and its
      function in the disease process. 

PMID- 25574376
TI  - Nanodelivery of Parthenolide Using Functionalized Nanographene Enhances its
      Anticancer Activity.
AB  - Advances in anticancer chemotherapy have been hindered by the lack of
      biocompatibility of new prospective drugs. One significant challenge concerns
      water insolubility, which compromises the bioavailability of the drugs leading to
      increased dosage and higher systemic toxicity. To overcome these problems,
      nanodelivery has been established as a promising approach for increasing the
      efficacy and lowering the required dosage of chemotherapeutics. The naturally
      derived compound, parthenolide (PTL), is known for its anti-inflammatory and
      anticancer activity, but its poor water solubility limits its clinical value. In
      the present study, we have used carboxyl-functionalized nanographene (fGn)
      delivery to overcome the extreme hydrophobicity of this drug. A water-soluble PTL
      analog, dimethylamino parthenolide (DMAPT), was also examined for comparison with
      the anticancer efficacy of our PTL-fGn complex. Delivery by fGn was found to
      increase the anticancer/apoptotic effects of PTL (but not DMAPT) when delivered
      to the human pancreatic cancer cell line, Panc-1. The IC50 value for PTL
      decreased from 39 uM to 9.5 uM when delivered as a mixture with fGn. The IC50 of
      DMAPT did not decrease when delivered as DMAPT-fGn and was significantly higher
      than that for PTL-fGn. There were significant increases in ROS formation and in
      mitochondrial membrane disruption in Panc-1 cells after PTL-fGn treatment as
      compared to PTL treatment, alone. Increases in toxicity were also seen with
      apoptosis detection assays using flow cytometry, ethidium bromide/acridine
      orange/DAPI staining, and TUNEL. Thus, fGn delivery was successfully used to
      overcome the poor water solubility of PTL, providing a strategy for improving the
      effectiveness of this anticancer agent.

PMID- 25574379
TI  - The Life Cycle of the Parasitic Crustacean, Lernanthropus latis Yamaguti, 1954
      (Copepoda: Lernanthropidae), on Marine-Cultured Fish, Lates calcarifer, from
      Setiu Wetland, Terengganu.
AB  - Parasitic crustaceans of Lernanthropus latis were isolated from the host, the
      seabass, Lates calcarifer, obtained from a cage culture in Setiu Wetland,
      Terengganu. The adult females with egg were kept alive in vials containing 20 mL
      of filtered seawater and incubated at 30 degrees C. The eggs were monitored every
      hour and the hatching periods were recorded. Three developmental stages were
      observed, namely, nauplii I, nauplii II, and infective copepodid. The infective
      copepodids were then transferred into a tank containing 60 litres of seawater
      with 150 fingerlings for infection purpose. One fish was sacrificed every 24 hr
      to inspect the next developmental stage. As a result, six more stages were
      obtained within 298 hrs starting from the infection day. The stages were known as
      fixed copepodid I, fixed copepodid II, fixed copepodid III, fixed copepodid IV,
      preadult, and adult. Parasitic L. latis takes a 483 hr period to complete a life
      cycle. 

PMID- 25574378
TI  - In Vitro Study of Directly Bioprinted Perfusable Vasculature Conduits.
AB  - The ability to create three dimensional (3D) thick tissues is still a major
      tissue engineering challenge. It requires the development of a suitable vascular
      supply for an efficient media exchange. An integrated vasculature network is
      particularly needed when building thick functional tissues and/or organs with
      high metabolic activities, such as the heart, liver and pancreas. In this work,
      human umbilical vein smooth muscle cells (HUVSMCs) were encapsulated in sodium
      alginate and printed in the form of vasculature conduits using a coaxial
      deposition system. Detailed investigations were performed to understand the
      dehydration, swelling and degradation characteristics of printed conduits. In
      addition, because perfusional, permeable and mechanical properties are unique
      characteristics of natural blood vessels, for printed conduits these properties
      were also explored in this work. The results show that cells encapsulated in
      conduits had good proliferation activities and that their viability increased
      during prolonged in vitro culture. Deposition of smooth muscle matrix and
      collagen was observed around the peripheral and luminal surface in long-term
      cultured cellular vascular conduit through histology studies. 

PMID- 25574377
TI  - Kinetic Monte Carlo simulations of the assembly of filamentous biomacromolecules
      by dimer addition mechanism.
AB  - In cells, several important biomacromolecules form oligomers through a dimer
      addition mechanism. Rate equations based on mean field approximations are usually
      employed to describe the assembly process. However, such equations often require
      multiple assumptions that mask some detailed changes of the biomolecular
      configurations during aggregations. Here, we present a Kinetic Monte Carlo
      simulation scheme to account for the diffusion and rotation of dimers on two
      dimensional hexagonal lattices while naturally including the stochastic features.
      We investigate the effects of the interaction energy between dimers, the
      diffusion coefficient and the concentration of dimers on the aggregation by dimer
      addition mechanism. Our simulations identified unusual double-S shape evolutions
      of aggregation kinetics, which are probably associated with the formation of
      metastable clusters.

PMID- 25574380
TI  - Predicting visual outcomes for macula-off rhegmatogenous retinal detachment with
      optical coherence tomography.
AB  - Purpose. We evaluated the ability of novel optical coherence tomography (OCT)
      parameters to predict postoperative best-corrected visual acuity (BCVA) in macula
      off rhegmatogenous retinal detachment (RRD) eyes. Methods. We reviewed the
      medical records of 56 consecutive eyes with macula-off RRD. Clinical findings
      were analyzed including the relationship between preoperative OCT findings and 6
      month postoperative BCVA. Results. Six-month postoperative BCVA was significantly
      correlated with preoperative findings including retinal height at the fovea,
      total and inner layer cross-sectional macular area within 2 mm of the fovea, and
      preoperative BCVA (P < 0.001, P < 0.001, P = 0.001, and P < 0.001, resp.).
      Multiple regression analysis revealed that the duration of macular detachment and
      total cross-sectional macular area were independent factors predicting 6-month
      postoperative BCVA (P = 0.024 and P = 0.041, resp.). Conclusions. Measuring
      preoperative total cross-sectional area of the macular layer within 2 mm of the
      fovea with OCT is a useful and objective way to predict postoperative visual
      outcome in eyes with macula-off RRD. 

PMID- 25574381
TI  - Effects of misalignments in the retinal nerve fiber layer thickness measurements
      with spectral domain optical coherence tomography.
AB  - Purpose. To investigate misalignments (MAs) on retinal nerve fiber layer
      thickness (RNFLT) measurements obtained with Cirrus((c)) SD-OCT. Methods. This
      was a retrospective, observational, cross-sectional study. Twenty-seven healthy
      and 29 glaucomatous eyes of 56 individuals with one normal exam and another
      showing MA were included. MAs were defined as an improper alignment of vertical
      vessels in the en face image. MAs were classified in complete MA (CMA) and
      partial MA (PMA), according to their site: 1 (superior, outside the measurement
      ring (MR)), 2 (superior, within MR), 3 (inferior, within MR), and 4 (inferior,
      outside MR). We compared RNFLT measurements of aligned versus misaligned exams in
      all 4 sectors, in the superior area (sectors 1 + 2), inferior area (sectors 3 +
      4), and within the measurement ring (sectors 2 + 3). Results. RNFLT measurements
      at 12 clock-hour of eyes with MAs in the superior area (sectors 1 + 2) were
      significantly lower than those obtained in the same eyes without MAs (P = 0.043).
      No significant difference was found in other areas (sectors 1 + 2 + 3 + 4,
      sectors 3 + 4, and sectors 2 + 3). Conclusion. SD-OCT scans with superior MAs may
      present lower superior RNFLT measurements compared to aligned exams. 

PMID- 25574382
TI  - Correlation of optic nerve microcirculation with papillomacular bundle structure
      in treatment naive normal tension glaucoma.
AB  - Purpose. To assess the association between optic nerve head (ONH)
      microcirculation, central papillomacular bundle (CPB) structure, and visual
      function in eyes with treatment naive normal tension glaucoma (NTG). Methods.
      This study included 40 eyes of 40 patients with NTG and 20 eyes of 20 normal
      patients. We used laser speckle flowgraphy (LSFG) to measure mean blur rate (MBR)
      in all eyes and calculated the ratio of MBR in the horizontal quadrants of tissue
      area ONH (temporal/nasal ratio of MBR in the tissue area: T/N MT). Clinical
      findings also included retinal nerve fiber layer thickness (RNFLT) and ganglion
      cell complex thickness (GCCT) in the CPB and macular areas, best-corrected visual
      acuity (BCVA), mean deviation (MD), and refractive error. Results. T/N MT was
      correlated with both BCVA and MD. The OCT parameters most highly correlated with
      T/N MT were macular RNFLT and mid-CPB RNFLT. Furthermore, T/N MT, mid-CPB RNFLT,
      and macular RNFLT were higher in NTG than in normal eyes. A discrimination
      analysis revealed that T/N MT and refractive error were independent factors
      indicating NTG. Conclusions. Our results suggest that T/N MT is a candidate
      biomarker of NTG. Furthermore, T/N MT reflects visual function, including acuity
      and sensitivity, and CPB structure. 

PMID- 25574383
TI  - Effects of stability of base pairs containing an oxazolone on DNA elongation.
AB  - The nucleoside 2,2,4-triamino-5(2H)-oxazolone (Oz) can result from oxidative
      damage to guanine residues in DNA. Despite differences among the three
      polymerases (Pol beta, KF exo(-), and Pol eta) regarding nucleotide incorporation
      patterns opposite Oz, all three polymerases can incorporate guanine opposite Oz.
      Based on ab initio calculations, we proposed a structure for a stable Oz:G base
      pair. Here, to assess the stability of each Oz-containing base pair (Oz:G, Oz:A,
      Oz:C, and Oz:T) upon DNA replication, we determined the efficiency of Pol beta-,
      KF exo(-)-, or Pol eta-catalyzed primer extension beyond each base pair. With
      each polymerase, extension beyond Oz:G was more efficient than that beyond Oz:A,
      Oz:C, or Oz:T. Moreover, thermal denaturation studies revealed that the T m value
      for the duplex containing Oz:G was significantly higher than those obtained for
      duplexes containing Oz:A, Oz:C, or Oz:T. Therefore, the results from ab initio
      calculations along with those from DNA replication assays and thermal
      denaturation experiments supported the conclusion that Oz:G is the most stable of
      the Oz-containing base pairs. 

PMID- 25574384
TI  - A Fractional Factorial Design to Study the Effect of Process Variables on the
      Preparation of Hyaluronidase Loaded PLGA Nanoparticles.
AB  - The present study was initiated to understand the effect of PLGA concentration,
      PVA concentration, internal-external phase ratio, homogenization speed, and
      homogenization time on mean particle size, zeta potential, and percentage drug
      encapsulation using fractional factorial design. Using PLGA (50-50) as the
      carrier, hyaluronidase loaded PLGA nanoparticles were prepared using double
      emulsion solvent evaporation technique. The particle size was analyzed by dynamic
      light scattering technique and protein content by Lowry method. The study showed
      that homogenization speed as an independent variable had maximum effect on
      particle size and zeta potential. Internal-external phase volume ratio had
      maximum effect on drug encapsulation. Mean particle size also had high dependency
      on the combined effect of PVA concentration and phase volume ratio. Using
      fractional factorial design particle size of <400 nm, zeta potential of <-30 mV,
      and percentage encapsulation of 15-18% were achieved. 

PMID- 25574385
TI  - Assessment of serum enzymatic antioxidant levels in patients with recurrent
      aphthous stomatitis: a case control study.
AB  - Background and Aim. Recurrent aphthous stomatitis (RAS) is a common oral mucosal
      disorder characterized by recurrent, painful oral aphthae. Despite extensive
      research, the exact etiology of RAS remains elusive. Recently oxidant-antioxidant
      imbalance of the body has been implicated in the pathogenesis of recurrent
      aphthous stomatitis. Thus, the aim of the study was to evaluate the enzymatic
      antioxidant levels in patients with recurrent aphthous stomatitis. Materials and
      Methods. The serum levels of superoxide dismutase (SOD), glutathione peroxidase
      (GPx), and catalase (CAT) were measured in 30 patients with recurrent aphthous
      stomatitis and compared to the control group, which included 30 healthy subjects.
      Student's t-test was performed for statistical evaluation. Results. The mean
      levels of superoxide dismutase (130.2 +/- 15.94 U/mL) and glutathione peroxidase
      (3527.93 +/- 488.32 U/L) were found to be significantly lower in study group as
      compared to control group (211.9 +/- 20.93 U/mL, 8860.93 +/- 1105.31 U/L, resp.)
      (P = 0.000) while level of catalase in study group was significantly higher when
      compared to control group (10981.00 +/- 1018.07 U/mL versus 9764.00 +/- 1621.19
      U/mL) (P = 0.000). Conclusion. Enzymatic antioxidant system is impaired in
      recurrent aphthous stomatitis patients and seems to play a crucial role in its
      pathogenesis. 

PMID- 25574386
TI  - Understanding barriers and facilitators to healthy eating and active living in
      rural communities.
AB  - Objective. Studies demonstrate that people's food and physical activity (PA)
      environments influence behavior, yet research examining this in rural communities
      is limited. Methods. Focus groups of 8-15 women were conducted in rural
      communities in seven US states. Questions were designed to identify factors
      within residents' food and PA environments they felt helped or hindered them from
      eating healthfully and being physically active. Results. Participants were aged
      30-84 years; mean (SD) = 61 (14) (N = 95). On average, communities had fewer than
      5,000 residents. Limited time, social norms, and distances from or lack of
      exercise facilities were common PA barriers. Facilitators for PA included social
      support, dog walking, and availability of affordable facilities. Healthy eating
      barriers included the perception that healthy foods were too expensive;
      calorically dense large portion sizes served at family meals; and frequency of
      eating foods away from home, which were perceived as generally unhealthy. Healthy
      eating supports included culture/value around local food gathering (e.g., hunting
      and gardening) and preservation (e.g., canning and smoking). Friends and family
      were frequently identified as key influencers of eating and PA behavior.
      Conclusions. Targeting both social and built environment factors, particularly
      those unique to rural locales, may enhance support for healthy eating and PA
      behavior change interventions. 

PMID- 25574387
TI  - Going around in a Circle: A Norwegian Study of Suicidal Experiences in Old Age.
AB  - Depression has repeatedly been found to be a risk factor for completed suicide,
      particularly when coupled with a pervasive sense of hopelessness. The aim of this
      study was to evaluate depressed older persons' suicidal experiences. Data were
      collected by means of individual in-depth interviews with nine informants living
      in two districts of Norway. A hermeneutic analysis was performed. One main theme:
      Going around in a circle and two themes: being alone without meaning in life and
      struggling to achieve reconciliation emerged from the analysis. An important
      implication for mental healthcare practice is the need to develop a person's
      ability to shape and take control of her/his life. The healthcare organisation
      must be committed to a plan that sets out strategies enabling suicidal
      individuals to avoid the negative experience of meaninglessness. It was concluded
      that suicidal depressed elderly persons need help to escape from their desperate
      situation. More research is urgently required in order to prevent suicide in
      depressed elderly persons whose emotional pain is unbearable. 

PMID- 25574388
TI  - Past Cigarette Smoking Is More Common among Those with Cholinergic Than
      Noncholinergic Dementias.
AB  - Background. Patients with progressive dementing disorders associated with
      cortical cholinergic dysfunction gradually develop cholinergic deficits many
      years before symptom onset and may begin to smoke cigarettes during midlife as a
      form of self-medication. The aim of this study was to compare self-reported past
      smoking rates between those with and without cholinergic dementias, to determine
      if those who developed cholinergic dementias were more likely to smoke during
      midlife than those who did not. Methods. Retrospective cross-sectional study of
      past smoking status among patients treated at an outpatient clinic during a three
      year period. Results. A total of 440 patients were evaluated during the study
      period, including 224 with cholinergic dementias and 216 with noncholinergic
      dementias and controls. Past smoking rates were greater among those with
      cholinergic dementias compared to those without cholinergic dementias (43.92%
      versus 26.96%, P = 0.012). Additionally, smokers with cholinergic dementias
      reported significantly greater mean pack-years of smoking (P = 0.038).
      Conclusions. Greater midlife smoking rates and greater pack-years of smoking were
      associated with cholinergic dementias. These results suggest midlife smoking may
      be an early indicator for those developing brain cholinergic deficits related to
      progressive dementing disorders and support initiating treatment prior to symptom
      onset in cholinergic dementias. 

PMID- 25574389
TI  - Low dose x-ray sources and high quantum efficiency sensors: the next challenge in
      dental digital imaging?
AB  - Objective(s). The major challenge encountered to decrease the milliamperes (mA)
      level in X-ray imaging systems is the quantum noise phenomena. This investigation
      evaluated dose exposure and image resolution of a low dose X-ray imaging (LDXI)
      prototype comprising a low mA X-ray source and a novel microlens-based sensor
      relative to current imaging technologies. Study Design. A LDXI in static (group
      1) and dynamic (group 2) modes was compared to medical fluoroscopy (group 3),
      digital intraoral radiography (group 4), and CBCT scan (group 5) using a dental
      phantom. Results. The Mann-Whitney test showed no statistical significance (alpha
      = 0.01) in dose exposure between groups 1 and 3 and 1 and 4 and timing exposure
      (seconds) between groups 1 and 5 and 2 and 3. Image resolution test showed group
      1 > group 4 > group 2 > group 3 > group 5. Conclusions. The LDXI proved the
      concept for obtaining a high definition image resolution for static and dynamic
      radiography at lower or similar dose exposure and smaller pixel size,
      respectively, when compared to current imaging technologies. Lower mA at the X
      ray source and high QE at the detector level principles with microlens could be
      applied to current imaging technologies to considerably reduce dose exposure
      without compromising image resolution in the near future. 

PMID- 25574390
TI  - Epicardial fat thickness as cardiovascular risk factor and therapeutic target in
      patients with rheumatoid arthritis treated with biological and nonbiological
      therapies.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with high
      cardiovascular morbidity and mortality. Epicardial adipose tissue (EAT) thickness
      may act as a therapeutic target during treatments with drugs modulating the
      adipose tissue. We evaluate EAT thickness in RA patients treated with biological
      and nonbiological disease-modifying antirheumatic drugs (DMARDs). A cross
      sectional study was conducted with a cohort of 34 female RA patients and 16
      controls matched for age and body mass index (BMI). Plasma glucose, basal
      insulin, plasma lipids, and high-sensitivity C-reactive protein (hs-CRP) were
      assessed. EAT thickness and left ventricular mass (LVM) were measured by
      echocardiography. No significant differences in waist circumference (WC), blood
      pressure, fasting blood glucose, basal insulin, and lipid parameters were found
      between the groups. The control group showed lower concentrations (P = 0.033) of
      hs-CRP and LVM (P = 0.0001) than those of the two RA groups. Patients treated
      with TNF-alpha inhibitors showed significantly lower EAT thickness than those
      treated with nonbiological DMARDs (8.56 +/- 1.90 mm versus 9.71 +/- 1.45 mm; P =
      0.04). Women with no RA revealed reduced EAT thickness (5.39 +/- 1.52 mm) as
      compared to all RA patients (P = 0.001). Results suggest that RA patients have
      greater EAT thickness than controls regardless of BMI and WC. 

PMID- 25574391
TI  - Attention-Deficit Hyperactive Disorder among Primary School Children in Menoufia
      Governorate, Egypt.
AB  - Background. Attention-deficit hyperactivity disorder (ADHD) is the most commonly
      diagnosed behavioral problem in children. Global variations in diagnostic
      criteria and rating scales of ADHD either by DSM-IV or ICD 10 may contribute to
      variations in its prevalence. Objectives. The study was conducted to estimate the
      prevalence of ADHD and to determine its risk factors. Methodology. A cross
      section comparative study was conducted in a randomly selected four primary
      schools in Menoufia governorate, Egypt. All children after a valid consent of
      their parents (N. 1362) were subjected to complete history taking, medical and
      psychological assessment, and IQ estimation. Their parents and teachers were
      subjected to the corresponding Arabic forms of Conner's questionnaire. Suspected
      cases were confirmed and categorized by DSM-IV criteria. The sample was divided
      into cases and controls to study the risk factors. Results. Prevalence of ADHD
      was 6.9% and the male : female ratio was 3.5 : 1. The main risk factors were
      neonatal problems (OR = 4.3), family history of psychiatric and medical illnesses
      (OR = 3.5 and 2.8), and male gender (OR = 2.9). Conclusion. Prevalence of ADHD
      among Menoufia school children was 6.9%. Dealing with its risk factors is
      mandatory for prevention, early management, and better outcome. 

PMID- 25574392
TI  - A Predictive HQSAR Model for a Series of Tricycle Core Containing MMP-12
      Inhibitors with Dibenzofuran Ring.
AB  - MMP-12 is a member of matrix metalloproteinases (MMPs) family involved in
      pathogenesis of some inflammatory based diseases. Design of selective matrix MMPs
      inhibitors is still challenging because of binding pocket similarities among MMPs
      family. We tried to generate a HQSAR (hologram quantitative structure activity
      relationship) model for a series of MMP-12 inhibitors. Compounds in the series of
      inhibitors with reported biological activity against MMP-12 were used to
      construct a predictive HQSAR model for their inhibitory activity against MMP-12.
      The HQSAR model had statistically excellent properties and possessed good
      predictive ability for test set compounds. The HQSAR model was obtained for the
      26 training set compounds showing cross-validated q (2) value of 0.697 and
      conventional r (2) value of 0.986. The model was then externally validated using
      a test set of 9 compounds and the predicted values were in good agreement with
      the experimental results (r pred (2) = 0.8733). Then, the external validity of
      the model was confirmed by Golbraikh-Tropsha and r m (2) metrics. The color code
      analysis based on the obtained HQSAR model provided useful insights into the
      structural features of the training set for their bioactivity against MMP-12 and
      was useful for the design of some new not yet synthesized MMP-12 inhibitors. 

PMID- 25574393
TI  - Molecular Modeling Studies of Thiophenyl C-Aryl Glucoside SGLT2 Inhibitors as
      Potential Antidiabetic Agents.
AB  - A QSAR study on thiophenyl derivatives as SGLT2 inhibitors as potential
      antidiabetic agents was performed with thirty-three compounds. Comparison of the
      obtained results indicated the superiority of the genetic algorithm over the
      simulated annealing and stepwise forward-backward variable method for feature
      selection. The best 2D QSAR model showed satisfactory statistical parameters for
      the data set (r (2) = 0.8499, q (2) = 0.8267, and pred_r (2) = 0.7729) with four
      descriptors describing the nature of substituent groups and the environment of
      the substitution site. Evaluation of the model implied that electron-rich
      substitution position improves the inhibitory activity. The good predictive 3D
      QSAR models by k-nearest neighbor (kNN) method for molecular field analysis (MFA)
      have cross-validated coefficient q (2) value of 0.7663 and predicted r (2) value
      of 0.7386. The results have showed that thiophenyl groups are necessary for
      activity and halogen, bulky, and less bulky groups in thiophenyl nucleus enhanced
      the biological activity. These studies are promising for the development of novel
      SGLT2 inhibitor, which may have potent antidiabetic activity. 

PMID- 25574394
TI  - Protective effect of quercetin on melphalan-induced oxidative stress and impaired
      renal and hepatic functions in rat.
AB  - One major challenge with the use of anticancer agents is the phenomenon of drug
      induced toxicity. Melphalan (MPLN) is an alkylating anticancer agent, while
      quercetin (QCT) is an antioxidant. We investigated the protective role of
      quercetin against MPLN-induced toxicity. Twenty-five male Wistar rats (160-170 g)
      were randomized into five treatment groups; (I) control, (II) MPLN (0.2 mg/kg
      b.w.), (III) pre-treated with QCT (20 mg/kg b.w.) for 7 days followed by MPLN
      (0.2 mg/kg b.w.) for 7 days, (IV) cotreated with QCT (20 mg/kg b.w.) and MPLN
      (0.2 mg/kg b.w.) for 7 days, and (V) QCT (20 mg/kg b.w.) alone. MPLN caused a
      significant increase in plasma bilirubin, urea, and creatinine by 122.2%, 102.3%,
      and 188%, respectively (P < 0.05). Similarly, plasma ALP, ALT, AST, and gamma-GT
      activities increased significantly by 57.9%, 144.3%, 71.3%, and 307.2%,
      respectively, relative to control. However, pre or cotreatment with QCT
      ameliorated the levels of renal and hepatic function indices. Hepatic ascorbic
      acid and GSH and activities of glutathione-S-transferase, SOD, and catalase
      decreased significantly by 36.2%, 188%, 46.5%, 34.4%, and 55.2%, respectively,
      followed by increase in MDA content by 46.5% relative to control. Pre- and
      cotreatment with QCT reestablished the hepatic antioxidant status and lipid
      peroxidation. Overall, quercetin protected against MPLN-induced renal and hepatic
      toxicity in rats. 

PMID- 25574396
TI  - Effect of Inhaling Cymbopogon martinii Essential Oil and Geraniol on Serum
      Biochemistry Parameters and Oxidative Stress in Rats.
AB  - The effects of the inhalation of Cymbopogon martinii essential oil (EO) and
      geraniol on Wistar rats were evaluated for biochemical parameters and hepatic
      oxidative stress. Wistar rats were divided into three groups (n = 8): G1 was
      control group, treated with saline solution; G2 received geraniol; and G3
      received C. martinii EO by inhalation during 30 days. No significant differences
      were observed in glycemia and triacylglycerol levels; G2 and G3 decreased (P <
      0.05) total cholesterol level. There were no differences in serum protein, urea,
      aspartate aminotransferase activity, and total hepatic protein. Creatinine levels
      increased in G2 but decreased in G3. Alanine aminotransferase activity and lipid
      hydroperoxide were higher in G2 than in G3. Catalase and superoxide dismutase
      activities were higher in G3. C. martinii EO and geraniol increased glutathione
      peroxidase. Oxidative stress caused by geraniol may have triggered some degree of
      hepatic toxicity, as verified by the increase in serum creatinine and alanine
      aminotransferase. Therefore, the beneficial effects of EO on oxidative stress can
      prevent the toxicity in the liver. This proves possible interactions between
      geraniol and numerous chemical compounds present in C. martinii EO. 

PMID- 25574397
TI  - Evaluation of a community reintegration outpatient program service for community
      dwelling persons with spinal cord injury.
AB  - Objective. To evaluate the effectiveness of a community reintegration outpatient
      (CROP) service for promoting well-being and community participation following
      spinal cord injury (SCI). Participants. Community-dwelling adults (N = 14) with
      traumatic and nontraumatic SCI. Interventions. The CROP service is a 12-week (1 *
      week; 120 minutes) interprofessional closed therapeutic education service. Main
      Outcome Measure(s). Moorong Self-Efficacy Scale (MSES); Impact on Participation
      and Autonomy (IPA); Positive Affect and Negative Affect Scale (PANAS); Coping
      Inventory of Stressful Situations (CISS); World Health Organization Quality of
      Life (WHOQOL-BREF); semistructured qualitative interviews. Methods. Twenty-one
      participants were recruited from two subsequent CROP services, with only 14
      persons completing all data assessments. Data were collected at baseline (week
      0), at exit (week 12), and at a three-month follow-up. Semistructured interviews
      were conducted at exit. Results. Self-efficacy (MSES) and positive affect (PANAS)
      improved from baseline to exit (P < .05), but the changes were not maintained at
      follow-up. Qualitative analysis identified four major themes related to
      therapeutic benefits: (1) role of self; (2) knowledge acquisition; (3) skill
      application; and (4) group processes. Conclusions. Participation in a therapeutic
      education service has the potential to improve well-being in persons with SCI,
      but there is a need to identify strategies to maintain long-term gains. 

PMID- 25574398
TI  - Risk of second cancers in merkel cell carcinoma: a meta-analysis of population
      based cohort studies.
AB  - The risk of second cancers in Merkel cell carcinoma (MCC) remains uncertain since
      risk estimates vary worldwide. The global MCC population is growing and there is
      a demand for better knowledge of prognosis of this disease. The Cochrane Database
      of Systematic Reviews, MEDLINE, and EMBASE search engines were searched for the
      relevant literature between January 1999 and September 2014 by use of explicit
      search criteria. The main outcome was second malignancies associated with MCC
      patients measured by standardized incidence ratios (SIRs) or other estimates of
      risks. Five papers fulfilled the inclusion criteria and reported SIRs of second
      cancer in MCC which varied from 1.07 to 2.80. Performing meta-analysis using
      random effects model revealed that there was an increased risk for second
      malignancies due to MCC (SIR, 1.52; 95% CI, 1.10-2.11). There was a significant
      increase in risk for malignant melanoma (SIR, 3.09; 95% CI, 2.02-4.73) as
      compared to all common second malignancies among the studies. Updated knowledge
      about risk of second malignancies in MCC will help in better assessment of the
      disease prognosis and will help in optimizing the medical and surgical treatment,
      radiotherapy, follow-up, and surveillance procedures. 

PMID- 25574395
TI  - A survey of computational intelligence techniques in protein function prediction.
AB  - During the past, there was a massive growth of knowledge of unknown proteins with
      the advancement of high throughput microarray technologies. Protein function
      prediction is the most challenging problem in bioinformatics. In the past, the
      homology based approaches were used to predict the protein function, but they
      failed when a new protein was different from the previous one. Therefore, to
      alleviate the problems associated with homology based traditional approaches,
      numerous computational intelligence techniques have been proposed in the recent
      past. This paper presents a state-of-the-art comprehensive review of various
      computational intelligence techniques for protein function predictions using
      sequence, structure, protein-protein interaction network, and gene expression
      data used in wide areas of applications such as prediction of DNA and RNA binding
      sites, subcellular localization, enzyme functions, signal peptides, catalytic
      residues, nuclear/G-protein coupled receptors, membrane proteins, and pathway
      analysis from gene expression datasets. This paper also summarizes the result
      obtained by many researchers to solve these problems by using computational
      intelligence techniques with appropriate datasets to improve the prediction
      performance. The summary shows that ensemble classifiers and integration of
      multiple heterogeneous data are useful for protein function prediction. 

PMID- 25574399
TI  - Tumor angiogenesis therapy using targeted delivery of Paclitaxel to the
      vasculature of breast cancer metastases.
AB  - Breast cancer aberrantly expresses tissue factor (TF) in cancer tissues and
      cancer vascular endothelial cells (VECs). TF plays a central role in cancer
      angiogenesis, growth, and metastasis and, as such, is a target for therapy and
      drug delivery. TF is the cognate receptor of factor VIIa (fVIIa). We have coupled
      PTX (paclitaxel, also named Taxol) with a tripeptide, phenylalanine-phenylalanine
      arginine chloromethyl ketone (FFRck) and conjugated it with fVIIa. The key aim of
      the work is to evaluate the antiangiogenic effects of PTX-FFRck-fVIIa against a
      PTX-resistant breast cancer cell line. Matrigel mixed with VEGF and MDA-231 was
      injected subcutaneously into the flank of athymic nude mice. Animals were treated
      by tail vein injection of the PTX-FFRck-fVIIa conjugate, unconjugated PTX, or
      PBS. The PTX-FFRck-fVIIa conjugate significantly reduces microvessel density in
      matrigel (p < 0.01-0.05) compared to PBS and unconjugated PTX. The breast cancer
      lung metastasis model in athymic nude mice was developed by intravenous injection
      of MDA-231 cells expressing luciferase. Animals were similarly treated
      intravenously with the PTX-FFRck-fVIIa conjugate or PBS. The conjugate
      significantly inhibits lung metastasis as compared to the control, highlighting
      its potential to antagonize angiogenesis in metastatic carcinoma. In conclusion,
      PTX conjugated to fVIIa is a promising therapeutic approach for improving
      selective drug delivery and inhibiting angiogenesis. 

PMID- 25574402
TI  - Dental Management of a 14-Year-Old with Cockayne Syndrome under General
      Anesthesia.
AB  - Cockayne's syndrome is a rare, autosomal recessive disorder characterized
      clinically by cachectic dwarfism, cutaneous photosensitivity, loss of adipose
      tissue, mental retardation, skeletal and neurological abnormalities, and
      pigmentary degeneration of the retina. Dental caries is a common finding. Dental
      rehabilitation of a 14-year-old male with Cockayne's syndrome is presented. 

PMID- 25574401
TI  - Sesamol: a natural phenolic compound with promising anticandidal potential.
AB  - We investigated the antifungal effects of sesamol (Ses), a natural phenolic
      compound, and exemplified that it could be mediated through disruption of
      calcineurin signaling pathway in C. albicans, a human fungal pathogen. The
      repertoire of antifungal activity not only was limited to C. albicans and its six
      clinical isolates tested but also was against non-albicans species of Candida.
      Interestingly, the antifungal effect of Ses affects neither the MDR efflux
      transporter activity nor passive diffusion of drug. We found that C. albicans
      treated with Ses copies the phenotype displayed by cells having defect in
      calcineurin signaling leading to sensitivity against alkaline pH, ionic,
      membrane, salinity, endoplasmic reticulum, and serum stresses but remained
      resistant to thermal stress. Furthermore, the ergosterol levels were
      significantly decreased by 63% confirming membrane perturbations in response to
      Ses as also visualized through transmission electron micrographs. Despite the
      fact that Ses treatment mimics the phenotype of compromised calcineurin
      signaling, it was independent of cell wall integrity pathway as revealed by spot
      assays and the scanning electron micrographs. Taken together, the data procured
      from this study clearly ascertains that Ses is an effectual antifungal agent that
      could be competently employed in treating Candida infections. 

PMID- 25574403
TI  - Gastric metastasis of ectopic breast cancer mimicking axillary metastasis of
      primary gastric cancer.
AB  - Ectopic breast tissue has the ability to undergo all the pathological changes of
      the normal breast, including breast cancer. Gastrointestinal metastasis of breast
      cancer is rarely observed and it is very difficult to differentiate gastric
      metastases from primary gastric cancer. We present a case of 52-year-old female,
      who suffered from abdominal pain. Physical examination showed a palpable mass in
      the left anterior axilla and computerized tomography revealed gastric wall
      thickening with linitis plastica. When gastroscopic biopsy showed no signs of
      malignancy, excisional biopsy was performed in the left axilla. Histological
      examination revealed invasive lobular carcinoma of the breast, consistent with
      ectopic breast cancer. Further gastroscopic submucosal biopsies and
      immunohistochemical studies revealed gastric metastases of invasive lobular
      carcinoma. Axillary ectopic breast tissue carcinomas can mimic axillary
      lymphadenopathies. Additionally, gastric metastasis of breast cancer is an
      uncommon but possible condition. To the best of our knowledge, this is the first
      report of ectopic breast cancer with gastric metastasis. 

PMID- 25574404
TI  - Visceral leishmaniasis: a differential diagnosis to remember after bone marrow
      transplantation.
AB  - Leishmania infection in immunocompromised hosts is reported in the literature,
      mostly concerning human immunodeficiency virus infected patients. It is not well
      characterized in the context of stem cell transplantation. We report a rare case
      clinical case of visceral leishmaniasis after allogeneic bone marrow
      transplantation. A 50-year-old Caucasian male was referred to allogeneic bone
      marrow transplantation with a high-risk acute lymphoblastic B leukemia in first
      complete remission. Allogeneic SCT was performed with peripheral blood stem cells
      from an unrelated Portuguese matched donor. In the following months, patient
      developed mild fluctuating cytopenias, mostly thrombocytopenia (between 60 and
      80*10(9)/L). The only significant complaint was intermittent tiredness. The
      common causes for thrombocytopenia in this setting were excluded-no evidence of
      graft versus host disease, no signs of viral or bacterial infection, and no signs
      of relapsed disease/dysplastic changes. The bone marrow smear performed 12 months
      after transplantation revealed an unsuspected diagnosis: a massive bone marrow
      infiltration with amastigotes. 

PMID- 25574405
TI  - Mild clinical course of severe Fever with thrombocytopenia syndrome virus
      infection in an elderly Japanese patient.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious and
      hemorrhagic disease recently described in China and western Japan. A 71-year-old
      healthy Japanese woman noticed a tick biting her after harvesting in an orchard
      and removed it herself. She developed diarrhea, anorexia, and chills eight days
      later. Because these symptoms continued, she visited a primary care physician 6
      days after the onset. Laboratory data revealed thrombocytopenia, leukocytopenia,
      and elevated liver enzymes. She was then referred to our hospital. Although not
      completely fulfilling the diagnostic criteria used in a retrospective study in
      Japan, SFTS was suspected, and we detected SFTS virus in the patient's blood
      using RT-PCR. However, she recovered without intensive treatment and severe
      complications 13 days after the onset. In this report, we present a mild clinical
      course of SFTS virus infection in Japan in detail. 

PMID- 25574406
TI  - Acute tubular necrosis after ingestion of a fertilizer containing sodium
      silicate.
AB  - Silica nephropathy occurs after chronic heavy exposure to silica, resulting in
      the development of chronic kidney disease and progression to end-stage renal
      disease. However, acute kidney injury due to silica exposure is rare and its
      renal pathology remains unclear. Here, we report a case of acute sodium silica
      poisoning presenting as acute kidney injury. A 42-year-old man ingested a
      fertilizer containing sodium silicate. His serum creatinine increased by 5.06
      mg/dL from 1.1 mg/dL 2 days after silicate ingestion. Owing to the decline in
      kidney function despite fluid therapy, a kidney biopsy was performed. The kidney
      showed acute tubular necrosis without infiltration of inflammatory cells. On day
      5 of admission, hemodialysis was initiated to treat the hyperkalemia and
      oliguria, and treatment with methylprednisolone was initiated for the acute lung
      injury. The patient was administered 1 mg/kg of methylprednisolone intravenously
      daily for 2 weeks, followed by a 2-week taper. Hemodialysis was discontinued on
      day 10 and the patient's renal function recovered completely. However, he died on
      day 40 of hospitalization owing to complicated lung fibrosis and persistent
      pneumothorax/pneumomediastinum. 

PMID- 25574400
TI  - Type I diabetes mellitus: genetic factors and presumptive enteroviral etiology or
      protection.
AB  - We review type 1 diabetes and host genetic components, as well as epigenetics and
      viruses associated with type 1 diabetes, with added emphasis on the
      enteroviruses, which are often associated with triggering the disease. Genus
      Enterovirus is classified into twelve species of which seven (Enterovirus A,
      Enterovirus B, Enterovirus C, and Enterovirus D and Rhinovirus A, Rhinovirus B,
      and Rhinovirus C) are human pathogens. These viruses are transmitted mainly by
      the fecal-oral route; they may also spread via the nasopharyngeal route.
      Enterovirus infections are highly prevalent, but these infections are usually
      subclinical or cause a mild flu-like illness. However, infections caused by
      enteroviruses can sometimes be serious, with manifestations of
      meningoencephalitis, paralysis, myocarditis, and in neonates a fulminant sepsis
      like syndrome. These viruses are often implicated in chronic (inflammatory)
      diseases as chronic myocarditis, chronic pancreatitis, and type 1 diabetes. In
      this review we discuss the currently suggested mechanisms involved in the viral
      induction of type 1 diabetes. We recapitulate current basic knowledge and
      definitions. 

PMID- 25574407
TI  - Clinicoradiological Correlation of Macropsia due to Acute Stroke: A Case Report
      and Review of the Literature.
AB  - Dysmetropsia (macropsia, micropsia, teleopsia, or pelopsia) most commonly results
      from retinal pathologies, epileptic seizure, neoplastic lesions, viral infection,
      or psychoactive drugs. Vascular lesions are an uncommon cause of dysmetropsia.
      Vascular hemimicropsia, although rare, has been more frequently described in the
      literature, whereas hemimacropsia from acute ischemic injury is exceedingly rare.
      We describe a patient presenting in the emergency room (ER) with visual
      perception disturbances characterized by a distorted perception of the size of
      objects, compatible with left hemimacropsia. Magnetic resonance imaging (MRI) of
      the brain showed an acute occipitotemporal ischemic injury corresponding to the
      posterior cerebral artery (PCA) territory. The location of the lesion is
      consistent with previous case reports that suggest that hemimacropsia is
      associated with the occipitotemporal projection, which plays a decisive role in
      the visual identification of objects by interconnecting the striate, prestriate,
      and inferior temporal areas. The difference of our case as compared to previous
      case reports is that the lesion in our patient spared Brodmann area 17 (calcarine
      cortex) and therefore did not present symptoms of quadrantanopsia. Instead, the
      patient presented isolated hemimacropsia, therefore suggesting that the
      anatomical lesion causing hemimacropsia is located in the ventral portion of the
      occipitotemporal projection, more specifically Brodmann areas 18 (parastriate)
      and 19 (peristriate). 

PMID- 25574408
TI  - A case of ruptured splenic artery aneurysm in pregnancy.
AB  - Background. Rupture of a splenic artery aneurysm is rare complication of
      pregnancy that is associated with a significant maternal and fetal mortality.
      Case. A multiparous female presented in the third trimester with hypotension,
      tachycardia, and altered mental status. A ruptured splenic artery aneurysm was
      discovered at the time of laparotomy and cesarean delivery. The patient made a
      full recovery following resection of the aneurysm. The neonate survived but
      suffered severe neurologic impairment. Conclusion. The diagnosis of ruptured
      splenic artery aneurysm should be considered in a pregnant woman presenting with
      signs of intra-abdominal hemorrhage. Early intervention by a multidisciplinary
      surgical team is key to preserving the life of the mother and fetus. 

PMID- 25574409
TI  - Response to: Comment on "Complete Androgen Insensitivity Syndrome: Optimizing
      Diagnosis and Management".

PMID- 25574410
TI  - Cutaneous angiosarcoma of the foot: a case report and review of the literature.
AB  - Primary Angiosarcoma of the skin of the foot is very rare. Angiosarcoma is
      typically treated with resection and wide-field postoperative radiation therapy.
      Chemotherapy and radiation therapy have also been used. Regardless of the
      treatment, the risk of local and distant relapse remains high for this disease.
      We present a case of an elderly patient who developed cutaneous angiosarcoma of
      the foot. It posed as a diagnostic dilemma at presentation. Chronic lymphedema
      was a possible predisposing factor. Given his age, preexisting renal dysfunction,
      refusal of surgery, and preference not to receive chemotherapy, the patient was
      ultimately treated with definitive radiotherapy. We present this case because of
      its rare site, unique presentation and delay in diagnosis of the condition, and
      attainment of an excellent response to radiation at the time of follow-up. We
      also review the current literature on this topic. 

PMID- 25574411
TI  - Retrograde intramedullary nailing with a blocking pin technique for reduction of
      periprosthetic supracondylar femoral fracture after total knee arthroplasty:
      technical note with a compatibility chart of the nail to femoral component.
AB  - Periprosthetic fractures after total knee arthroplasty (TKA) present a clear
      management challenge, and retrograde intramedullary nails have recently gained
      widespread acceptance in treatment of these fractures. In two cases, we found a
      blocking screw technique, first reported by Krettek et al., was useful in the
      reduction of the fractures. Both patients attained preinjury mobility after
      intramedullary nailing. Moreover, we present a chart summarizing the notch
      designs of various femoral components because some prosthetic knee designs are
      not amenable to retrograde nailing. We hope this will be helpful in determining
      indications for retrograde nailing in periprosthetic fractures after TKA. 

PMID- 25574412
TI  - Magnifying endoscopy with narrow band imaging to determine the extent of
      resection in transoral robotic surgery of oropharyngeal cancer.
AB  - Transoral robotic surgery (TORS) is a less invasive treatment that is becoming
      popular all over the world. One of the most important factors for achieving
      success in TORS is the ability to determine the extent of resection during the
      procedure as the extent of resection in the laryngopharynx not only affects
      oncological outcomes but also directly affects swallowing and voice functions.
      Magnifying endoscopy with narrow band imaging (ME-NBI) is an innovative optical
      technology that provides high-resolution images and is useful in detecting early
      superficial pharyngeal cancers, which are difficult to detect by standard
      endoscopy. A 55-year-old male with superficial oropharyngeal cancer has been
      successfully treated by combining MB-NBI with TORS and MB-NBI was useful in
      determining the extent of resection. ME-NBI with TORS will make it possible to
      achieve a higher ratio of minimally invasive treatment in pharyngeal cancer. 

PMID- 25574413
TI  - Recurrent rhinosporidiosis: coblation assisted surgical resection-a novel
      approach in management.
AB  - Recurrent rhinosporidiosis is a chronic granulomatous disease with a known
      tendency to reoccur. Coblation EVAC 70 is a novel surgical tool which seems to
      provide excellent option in management of this notorious disease. We present an
      interesting case and the innovative approach in its management, using Coblation
      system. Introduction. Rhinosporidiosis seeberi causes a chronic granulomatous
      disease of upper airway, usually involving the nose and nasopharynx, and has a
      notorious tendency to reoccur. The current line of management is surgical
      excision of the lesion along with cauterization of the base, which does not
      prevent reoccurrence of the disease. Case Presentation. A 65-year-old male
      resident of rural India reported a history of breathing difficulty and change in
      voice. Patient is a Hindu priest by profession, who according to their rituals
      has to take bath in local pond or river. Conclusion. Rhinosporidiosis is a
      difficult to treat pathology due to its tendency to reoccur. Till date the
      management of the disease is far from satisfactory. Coblation system which has
      already found its roots in otorhinolaryngology can be used as a novel tool in
      surgical resection of recurrent rhinosporidiosis and has added advantage of low
      temperature dissection along with clear surgical field due to constant
      suctioning. 

PMID- 25574414
TI  - Hemangioblastoma in the lung: metastatic or primary lesions?
AB  - Hemangioblastoma primarily occurs in the CNS, most commonly in the posterior
      fossa. Extracranial locations are less common, and metastatic tumor involving the
      lung is exceedingly rare with only three cases previously reported. Two were
      autopsy studies in patients who died of complications of the CNS
      hemangioblastomas in 1943 and 1981, and the third was mentioned in a case report
      addendum providing follow-up information on hepatic hemangioblastoma in 1991. We
      report a case of a 48-year-old man who presented with multiple lung nodules
      treated by surgical excision. Pathological study revealed features classic for
      hemangioblastoma. The patient had a remote history of hemangioblastomas having
      been excised from the posterior fossa 7 and 20 years previously. This report
      details a fourth case of metastatic pulmonary hemangioblastoma. It is the first
      report on surgically resected hemangioblastomas from the lung of a living patient
      with histological and immunohistochemical characterization. 

PMID- 25574415
TI  - Spinal cord glioneuronal tumor with rosetted neuropil-like islands in pediatric
      age group.
AB  - Glioneuronal neoplasms are rare tumors. Recently, an unusual glioneuronal tumor
      histologically showing neuropil-like islands has been described. Here, we present
      such a tumor originating from spinal cord of a 14-year-old girl, who has
      scoliosis and urinary incontinence. Microscopically, the glial component was
      chiefly fibrillary astrocytic, punctuated by neuropil-like islands.
      Immunohistochemically, glial tissue was GFAP positive, and neuropil-like areas
      and big neurons were synaptophysin reactive. For astrocytic component Ki-67
      proliferation index was 1% and p53 was immunonegative. This case is unique in
      that in the literature it is the second reported case in pediatric age group that
      is located at spinal cord. 

PMID- 25574416
TI  - Radiofrequency ablation in the management of advanced stage thymomas: a case
      report on a novel multidisciplinary therapeutic approach.
AB  - We describe in this report a case of successful radiofrequency ablation of an
      unresectable stage III-type B3 thymoma, and we discuss the role of this novel
      approach in the management of patients with advanced stage thymoma. The patient,
      a 59-year-old Caucasian male underwent neoadjuvant chemotherapy with only a
      slight reduction of the mass. Subsequently, an explorative sternotomy and
      debulking were performed; before closing the thorax, radiofrequency ablation of
      the residual tumor was carried out and a partial necrosis of the mass was
      achieved. A further percutaneous radiofrequency ablation was performed
      subsequently, obtaining complete necrosis of the lesion. Successively, the
      patient underwent adjuvant radiotherapy. As a result of this multidisciplinary
      treatment, complete and stable response was obtained. It is hard to say which of
      the single treatments had the major impact on cure; nevertheless, the results
      obtained suggest that radiofrequency ablation must be taken into account for the
      treatment of advanced stage thymomas, and its effectiveness must be further
      assessed in future studies. 

PMID- 25574417
TI  - Lobar Collapse and Obliteration of Air Bronchogram Allowing Early Diagnosis of
      Endobronchial Aspergillus Infection following Hematopoietic Stem Cell
      Transplantation.
AB  - Endobronchial fungal infection (EBFI) is notoriously difficult to diagnose early
      since it may present few systemic features and does not cause characteristic
      parenchymal lesions on lung CT scanning. We report a 9-year-old girl who suffered
      extended neutropenia following graft failure after haematopoietic stem cell
      transplantation (HSCT) for severe aplastic anaemia. CT scan prior to
      retransplantation was normal despite persistent cough but lobar collapse was
      shown on repeat scan 16 days later. The probable diagnosis of EBFI (later proven
      on bronchoscopy) was only suspected when subsequent chest X-ray (CXR)
      demonstrated lack of an air bronchogram in the partially collapsed lung. Early
      radiological suspicion resulted in multiagent antifungal therapy followed by
      delayed lobectomy, and led to this being the first reported case of Aspergillus
      EBFI not to result in respiratory failure. 

PMID- 25574418
TI  - Gout initially mimicking rheumatoid arthritis and later cervical spine
      involvement.
AB  - Gout is clinically characterized by episodes of monoarthritis, but if not treated
      properly, it can lead to a chronic polyarthritis, which may eventually mimic
      rheumatoid arthritis (RA). We present the case of a 59-year-old man, with a
      history of symmetrical polyarthritis of the large and small joints with later
      development of subcutaneous nodules, which was initially misdiagnosed as RA,
      being treated with prednisone and methotrexate for a long period of time. He
      complained of occipital pain and paresthesia in his left upper limb, and computed
      tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of an
      expansive formation in the cervical spine with compression of the medulla. He was
      admitted for spinal decompressive surgery and the biopsy specimen demonstrated a
      gouty tophus. Chronic gout can mimic RA and rarely involves the axial skeleton,
      and thus its correct diagnosis and the implementation of adequate therapy can
      halt the development of such damaging complications. 

PMID- 25574419
TI  - Bisphosphonate-induced periprosthetic fracture: a cause of painful total hip
      arthroplasty.
AB  - Background. Cases have been reported in the literature of periprosthetic
      fractures associated with the use of bisphosphonates occurring in the long term
      following a Total Hip Replacement (THR). We report an interesting case of
      periprosthetic fracture secondary to bisphosphonate use only a few months after a
      THR. Case Report. A 72-year-old lady (on bisphosphonates for 10 years) underwent
      a THR for osteoarthritis. She was pain-free in the first four months
      postoperatively. Thereafter, she developed spontaneous onset of pain in the
      lateral aspect of her thigh and groin and found it difficult to weight-bear. X
      rays and blood tests were unremarkable. An ultrasound and MRI scan showed no
      evidence of effusion/collection or periprosthetic fracture. A radionuclide bone
      scan showed an abnormal appearance of the right femoral shaft. A subsequent CT
      scan showed an oblique vertical split on the anterior surface of the upper right
      femoral shaft. This stress fracture was managed nonoperatively with protected
      weight bearing. She has progressed well with good clinical and radiological signs
      of fracture healing. Conclusion. This case is an important addition to our
      knowledge that bisphosphonate-induced periprosthetic stress fractures can be a
      cause of hip pain only a few months following a THR. 

PMID- 25574421
TI  - Model Based Filtered Backprojection Algorithm: A Tutorial.
AB  - PURPOSE: People have been wandering for a long time whether a filtered
      backprojection (FBP) algorithm is able to incorporate measurement noise in image
      reconstruction. The purpose of this tutorial is to develop such an FBP algorithm
      that is able to minimize an objective function with an embedded noise model.
      METHODS: An objective function is first set up to model measurement noise and to
      enforce some constraints so that the resultant image has some pre-specified
      properties. An iterative algorithm is used to minimize the objective function,
      and then the result of the iterative algorithm is converted into the Fourier
      domain, which in turn leads to an FBP algorithm. The model based FBP algorithm is
      almost the same as the conventional FBP algorithm, except for the filtering step.
      RESULTS: The model based FBP algorithm has been applied to low-dose x-ray CT,
      nuclear medicine, and real-time MRI applications. Compared with the conventional
      FBP algorithm, the model based FBP algorithm is more effective in reducing noise.
      Even though an iterative algorithm can achieve the same noise-reducing
      performance, the model based FBP algorithm is much more computationally
      efficient. CONCLUSIONS: The model based FBP algorithm is an efficient and
      effective image reconstruction tool. In many applications, it can replace the
      state-of-the-art iterative algorithms, which usually have a heavy computational
      cost. The model based FBP algorithm is linear and it has advantages over a
      nonlinear iterative algorithm in parametric image reconstruction and noise
      analysis.

PMID- 25574420
TI  - Follistatin alleviates synovitis and articular cartilage degeneration induced by
      carrageenan.
AB  - Activins are proinflammatory cytokines which belong to the TGFbeta superfamily.
      Follistatin is an extracellular decoy receptor for activins. Since both activins
      and follistatin are expressed in articular cartilage, we hypothesized that
      activin-follistatin signaling participates in the process of joint inflammation
      and cartilage degeneration. To test this hypothesis, we examined the effects of
      follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by
      intra-articular injection of carrageenan was significantly alleviated by
      preinjection with follistatin. Macrophage infiltration into the synovial membrane
      was significantly reduced in the presence of follistatin. In addition,
      follistatin inhibited proteoglycan erosion induced by carrageenan in articular
      cartilage. These data indicate that activin-follistatin signaling is involved in
      joint inflammation and cartilage homeostasis. Our data suggest that follistatin
      can be a new therapeutic target for inflammation-induced articular cartilage
      degeneration. 

PMID- 25574422
TI  - Measuring the Strength of State-Level Alcohol Control Policies.
AB  - PURPOSE: We describe a multi-step method of coding the strength of 18 alcohol
      policies included in the Alcohol Policy Information System for each of the 50
      states. METHOD: After thoroughly reviewing each policy area, we chose components
      that were most important in categorizing the strength or restrictiveness of the
      policy using the following criteria: overall reach, enforceability, and
      implementation. We determined a unique coding scheme for each policy area.
      RESULTS: The total number of categories per policy area ranged from two to six,
      with categories numbered in an ordered sequence from least to most restrictive.
      We provide three examples of our coding schemes: Keg Registration, Underage
      Possession, and Sunday Sales. We also rank the states on their alcohol policy sum
      score. DISCUSSION: This study demonstrates how alcohol policies can be measured
      quantitatively, an important step for assessing the effects of alcohol policies
      on various outcomes.

PMID- 25574423
TI  - Trace cancer biomarker quantification using polystyrene-functionalized gold
      nanorods.
AB  - We demonstrate the application of polystyrene-functionalized gold nanorods
      (AuNRs) as a platform for surface enhanced Raman scattering (SERS) quantification
      of the exogenous cancer biomarker Acetyl Amantadine (AcAm). We utilize the
      hydrophobicity of the polystyrene attached to the AuNR surface to capture the
      hydrophobic AcAm from solution, followed by drying and detection using SERS. We
      achieve a detection limit of 16 ng/mL using this platform. This result shows
      clinical potential for low-cost early cancer detection. 

PMID- 25574424
TI  - Polarised stereo endoscope and narrowband detection for minimal access surgery.
AB  - Polarisation imaging has the potential to provide enhanced contrast based on
      variations in the optical properties, such as scattering or birefringence, of the
      tissue of interest. Examining the signal at different wavebands in the visible
      spectrum also allows interrogation of different depths and structures. A stereo
      endoscope has been adapted to allow snapshot acquisition of orthogonal linear
      polarisation images to generate difference of linear polarisation images. These
      images are acquired in three narrow bands using a triple-bandpass filter and pair
      of colour cameras. The first in vivo results, acquired during a surgical
      procedure on a porcine subject, are presented that show wavelength dependent
      variations in vessel visibility and an increase in contrast under polarised
      detection. 

PMID- 25574425
TI  - Quantifying the vascular response to ischemia with speckle variance optical
      coherence tomography.
AB  - Longitudinal monitoring techniques for preclinical models of vascular remodeling
      are critical to the development of new therapies for pathological conditions such
      as ischemia and cancer. In models of skeletal muscle ischemia in particular,
      there is a lack of quantitative, non-invasive and long term assessment of vessel
      morphology. Here, we have applied speckle variance optical coherence tomography
      (OCT) methods to quantitatively assess vascular remodeling and growth in a mouse
      model of peripheral arterial disease. This approach was validated on two
      different mouse strains known to have disparate rates and abilities of recovering
      following induction of hind limb ischemia. These results establish the potential
      for speckle variance OCT as a tool for quantitative, preclinical screening of pro
      and anti-angiogenic therapies. 

PMID- 25574427
TI  - Introduction to the BIOMED 2014 feature issue.
AB  - The guest editors introduce a feature issue containing papers based on research
      presented at the BIOMED 2014 conference, held in Miami, FL, April 26-30, 2014. 

PMID- 25574426
TI  - Three-dimensional motion correction using speckle and phase for in vivo computed
      optical interferometric tomography.
AB  - Over the years, many computed optical interferometric techniques have been
      developed to perform high-resolution volumetric tomography. By utilizing the
      phase and amplitude information provided with interferometric detection, post
      acquisition corrections for defocus and optical aberrations can be performed. The
      introduction of the phase, though, can dramatically increase the sensitivity to
      motion (most prominently along the optical axis). In this paper, we present two
      algorithms which, together, can correct for motion in all three dimensions with
      enough accuracy for defocus and aberration correction in computed optical
      interferometric tomography. The first algorithm utilizes phase differences within
      the acquired data to correct for motion along the optical axis. The second
      algorithm utilizes the addition of a speckle tracking system using temporally-
      and spatially-coherent illumination to measure motion orthogonal to the optical
      axis. The use of coherent illumination allows for high-contrast speckle patterns
      even when imaging apparently uniform samples or when highly aberrated beams
      cannot be avoided. 

PMID- 25574428
TI  - Automated method for the segmentation and morphometry of nerve fibers in large
      scale CARS images of spinal cord tissue.
AB  - A fully automated method for large-scale segmentation of nerve fibers from
      coherent anti-Stokes Raman scattering (CARS) microscopy images is presented. The
      method is specifically designed for CARS images of transverse cross sections of
      nervous tissue but is also suitable for use with standard light microscopy
      images. After a detailed description of the two-part segmentation algorithm, its
      accuracy is quantified by comparing the resulting binary images to manually
      segmented images. We then demonstrate the ability of our method to retrieve
      morphological data from CARS images of nerve tissue. Finally, we present the
      segmentation of a large mosaic of CARS images covering more than half the area of
      a mouse spinal cord cross section and show evidence of clusters of neurons with
      similar g-ratios throughout the spinal cord. 

PMID- 25574429
TI  - Terahertz spectroscopic imaging and properties of gastrointestinal tract in a rat
      model.
AB  - We have investigated basic properties of normal gastrointestinal (GI) tract
      tissues, including glandular stomach (GS), fore stomach (FS), large intestine
      (LI), small intestine (SI), and esophagus (ESO), from a rat model using terahertz
      (THz) reflection imaging and spectroscopy. The THz images collected from
      stratified squamous epithelia (SSE) of FS and ESO show a lower peak-to-peak value
      compared to those from columnar epithelia (CE) of GS, LI, or SI because the SSE
      contains less water than CE. The refractive index and absorption coefficient of
      FS were less than those of GS or LI, both having values similar to those of
      water. Additionally, we report internal reflection THz signals from ESO, although
      we were unable to determine the exact interface for this internal reflection. 

PMID- 25574430
TI  - Simultaneous decomposition of multiple hyperspectral data sets: signal recovery
      of unknown fluorophores in the retinal pigment epithelium.
AB  - Upon excitation with different wavelengths of light, biological tissues emit
      distinct but related autofluorescence signals. We used non-negative matrix
      factorization (NMF) to simultaneously decompose co-registered hyperspectral
      emission data from human retinal pigment epithelium/Bruch's membrane specimens
      illuminated with 436 and 480 nm light. NMF analysis was initialized with Gaussian
      mixture model fits and constrained to provide identical abundance images for the
      two excitation wavelengths. Spectra recovered this way were smoother than those
      obtained separately; fluorophore abundances more clearly localized within tissue
      compartments. These studies provide evidence that leveraging multiple co
      registered hyperspectral emission data sets is preferential for identifying
      biologically relevant fluorophore information. 

PMID- 25574431
TI  - Adaptive optics optical coherence tomography at 1 MHz.
AB  - Image acquisition speed of optical coherence tomography (OCT) remains a
      fundamental barrier that limits its scientific and clinical utility. Here we
      demonstrate a novel multi-camera adaptive optics (AO-)OCT system for
      ophthalmologic use that operates at 1 million A-lines/s at a wavelength of 790 nm
      with 5.3 MUm axial resolution in retinal tissue. Central to the spectral-domain
      design is a novel detection channel based on four high-speed spectrometers that
      receive light sequentially from a 1 * 4 optical switch assembly. Absence of
      moving parts enables ultra-fast (50ns) and precise switching with low insertion
      loss (-0.18 dB per channel). This manner of control makes use of all available
      light in the detection channel and avoids camera dead-time, both critical for
      imaging at high speeds. Additional benefit in signal-to-noise accrues from the
      larger numerical aperture afforded by the use of AO and yields retinal images of
      comparable dynamic range to that of clinical OCT. We validated system performance
      by a series of experiments that included imaging in both model and human eyes. We
      demonstrated the performance of our MHz AO-OCT system to capture detailed images
      of individual retinal nerve fiber bundles and cone photoreceptors. This is the
      fastest ophthalmic OCT system we know of in the 700 to 915 nm spectral band. 

PMID- 25574432
TI  - Ex vivo 4D visualization of aortic valve dynamics in a murine model with optical
      coherence tomography.
AB  - The heart and its mechanical components, especially the heart valves and
      leaflets, are under enormous strain and undergo fatigue, which impinge upon
      cardiac output. The knowledge about changes of the dynamic behavior and the
      possibility of early stage diagnosis could lead to the development of new
      treatment strategies. Animal models are suited for the development and evaluation
      of new experimental approaches and therefor innovative imaging techniques are
      necessary. In this study, we present the time resolved visualization of healthy
      and calcified aortic valves in an ex vivo artificially stimulated heart model
      with 4D optical coherence tomography and high-speed video microscopy. 

PMID- 25574433
TI  - Enhanced quantitative phase imaging in self-interference digital holographic
      microscopy using an electrically focus tunable lens.
AB  - Self-interference digital holographic microscopy (DHM) has been found particular
      suitable for simplified quantitative phase imaging of living cells. However, a
      main drawback of the self-interference DHM principle are scattering patterns that
      are induced by the coherent nature of the laser light which affect the resolution
      for detection of optical path length changes. We present a simple and efficient
      technique for the reduction of coherent disturbances in quantitative phase
      images. Therefore, amplitude and phase of the sample illumination are modulated
      by an electrically focus tunable lens. The proposed method is in particular
      convenient with the self-interference DHM concept. Results from the
      characterization of the method show that a reduction of coherence induced
      disturbances up to 70 percent can be achieved. Finally, the performance for
      enhanced quantitative imaging of living cells is demonstrated. 

PMID- 25574434
TI  - Characterizing the microstructures of biological tissues using Mueller matrix and
      transformed polarization parameters.
AB  - Mueller matrices can be used as a powerful tool to probe qualitatively the
      microstructures of biological tissues. Certain transformation processes can
      provide new sets of parameters which are functions of the Mueller matrix elements
      but represent more explicitly the characteristic features of the sample. In this
      paper, we take the backscattering Mueller matrices of a group of tissues with
      distinctive structural properties. Using both experiments and Monte Carlo
      simulations, we demonstrate qualitatively the characteristic features of Mueller
      matrices corresponding to different structural and optical properties. We also
      calculate two sets of transformed polarization parameters using the Mueller
      matrix transformation (MMT) and Mueller matrix polar decomposition (MMPD)
      techniques. We demonstrate that the new parameters can separate the effects due
      to sample orientation and present quantitatively certain characteristic features
      of these tissues. Finally, we apply the transformed polarization parameters to
      the unstained human cervix cancerous tissues. Preliminary results show that the
      transformed polarization parameters can provide characteristic information to
      distinguish the cancerous and healthy tissues. 

PMID- 25574435
TI  - Reflection-mode in vivo photoacoustic microscopy with subwavelength lateral
      resolution.
AB  - We developed a reflection-mode subwavelength-resolution photoacoustic microscopy
      system capable of imaging optical absorption contrast in vivo. The simultaneous
      high-resolution and reflection-mode imaging capacity of the system was enabled by
      delicately configuring a miniature high-frequency ultrasonic transducer tightly
      under a water-immersion objective with numerical aperture of 1.0. At 532-nm laser
      illumination, the lateral resolution of the system was measured to be ~320 nm.
      With this system, subcellular structures of red blood cells and B16 melanoma
      cells were resolved ex vivo; microvessels, including individual capillaries, in a
      mouse ear were clearly imaged label-freely in vivo, using the intrinsic optical
      absorption from hemoglobin. The current study suggests that, the optical
      absorption contrast, subwavelength resolution, and reflection-mode ability of the
      developed photoacoustic microscopy may empower a wide range of biomedical studies
      for visualizing cellular and/or subcellular structures. 

PMID- 25574436
TI  - Simultaneous optical coherence tomography and lipofuscin autofluorescence imaging
      of the retina with a single broadband light source at 480nm.
AB  - We accomplished spectral domain optical coherence tomography and auto
      fluorescence microscopy for imaging the retina with a single broadband light
      source centered at 480 nm. This technique is able to provide simultaneous
      structural imaging and lipofuscin molecular contrast of the retina. Since the two
      imaging modalities are provided by the same group of photons, their images are
      intrinsically registered. To test the capabilities of the technique we
      periodically imaged the retinas of the same rats for four weeks. The images
      successfully demonstrated lipofuscin accumulation in the retinal pigment
      epithelium with aging. The experimental results showed that the dual-modal
      imaging system can be a potentially powerful tool in the study of age-related
      degenerative retinal diseases. 

PMID- 25574437
TI  - Wavelet based feature extraction and visualization in hyperspectral tissue
      characterization.
AB  - Hyperspectral images of tissue contain extensive and complex information relevant
      for clinical applications. In this work, wavelet decomposition is explored for
      feature extraction from such data. Wavelet methods are simple and computationally
      effective, and can be implemented in real-time. The aim of this study was to
      correlate results from wavelet decomposition in the spectral domain with physical
      parameters (tissue oxygenation, blood and melanin content). Wavelet decomposition
      was tested on Monte Carlo simulations, measurements of a tissue phantom and
      hyperspectral data from a human volunteer during an occlusion experiment.
      Reflectance spectra were decomposed, and the coefficients were correlated to
      tissue parameters. This approach was used to identify wavelet components that can
      be utilized to map levels of blood, melanin and oxygen saturation. The results
      show a significant correlation (p <0.02) between the chosen tissue parameters and
      the selected wavelet components. The tissue parameters could be mapped using a
      subset of the calculated components due to redundancy in spectral information.
      Vessel structures are well visualized. Wavelet analysis appears as a promising
      tool for extraction of spectral features in skin. Future studies will aim at
      developing quantitative mapping of optical properties based on wavelet
      decomposition. 

PMID- 25574438
TI  - In vivo nonlinear spectral imaging as a tool to monitor early spectroscopic and
      metabolic changes in a murine cutaneous squamous cell carcinoma model.
AB  - Timely detection of cutaneous squamous cell carcinoma with non-invasive
      modalities like nonlinear spectral imaging (NLSI) can ensure efficient preventive
      or therapeutic measures for patients. In this study, in vivo NLSI was used to
      study spectral characteristics in murine skin treated with 7, 12
      dimethylbenz(a)anthracene. The results show that NLSI could detect emission
      spectral changes during the early preclinical stages of skin carcinogenesis.
      Analyzing these emission spectra using simulated band-pass filters at 450-460 nm
      and 525-535 nm, gave parameters that were expressed as a ratio. This ratio was
      increased and thus suggestive of elevated metabolic activity in early stages of
      skin carcinogenesis. 

PMID- 25574439
TI  - Accuracy of oxygen saturation and total hemoglobin estimates in the neonatal
      brain using the semi-infinite slab model for FD-NIRS data analysis.
AB  - Frequency domain near-infrared spectroscopy (FD-NIRS) is a non-invasive method
      for measuring optical absorption in the brain. Common data analysis procedures
      for FD-NIRS data assume the head is a semi-infinite, homogenous medium. This
      assumption introduces bias in estimates of absorption (MUa ), scattering (
      [Formula: see text]), tissue oxygen saturation (StO2), and total hemoglobin
      (HbT). Previous works have investigated the accuracy of recovered MUa values
      under this assumption. The purpose of this study was to examine the accuracy of
      recovered StO2 and HbT values in FD-NIRS measurements of the neonatal brain. We
      used Monte Carlo methods to compute light propagation through a neonate head
      model in order to simulate FD-NIRS measurements at 690 nm and 830 nm. We
      recovered MUa , [Formula: see text], StO2, and HbT using common analysis
      procedures that assume a semi-infinite, homogenous medium and compared the
      recovered values to simulated values. Additionally, we characterized the effects
      of curvature via simulations on homogenous spheres of varying radius. Lastly, we
      investigated the effects of varying amounts of extra-axial fluid. Curvature
      induced underestimation of MUa , [Formula: see text], and HbT, but had minimal
      effects on StO2. For the morphologically normal neonate head model, the mean
      absolute percent errors (MAPE) of recovered MUa values were 12% and 7% for 690 nm
      and 830 nm, respectively, when source-detector separation was at least 20 mm. The
      MAPE for recovered StO2 and HbT were 6% and 9%, respectively. Larger relative
      errors were observed (~20-30%), especially as StO2 and HbT deviated from normal
      values. Excess CSF around the brain caused very large errors in MUa , [Formula:
      see text], and HbT, but had little effect on StO2. 

PMID- 25574440
TI  - Quantitative elasticity measurement of urinary bladder wall using laser-induced
      surface acoustic waves.
AB  - The maintenance of urinary bladder elasticity is essential to its functions,
      including the storage and voiding phases of the micturition cycle. The bladder
      stiffness can be changed by various pathophysiological conditions. Quantitative
      measurement of bladder elasticity is an essential step toward understanding
      various urinary bladder disease processes and improving patient care. As a
      nondestructive, and noncontact method, laser-induced surface acoustic waves
      (SAWs) can accurately characterize the elastic properties of different layers of
      organs such as the urinary bladder. This initial investigation evaluates the
      feasibility of a noncontact, all-optical method of generating and measuring the
      elasticity of the urinary bladder. Quantitative elasticity measurements of ex
      vivo porcine urinary bladder were made using the laser-induced SAW technique. A
      pulsed laser was used to excite SAWs that propagated on the bladder wall surface.
      A dedicated phase-sensitive optical coherence tomography (PhS-OCT) system
      remotely recorded the SAWs, from which the elasticity properties of different
      layers of the bladder were estimated. During the experiments, series of
      measurements were performed under five precisely controlled bladder volumes using
      water to estimate changes in the elasticity in relation to various urinary
      bladder contents. The results, validated by optical coherence elastography, show
      that the laser-induced SAW technique combined with PhS-OCT can be a feasible
      method of quantitative estimation of biomechanical properties. 

PMID- 25574441
TI  - Blood vessel segmentation and width estimation in ultra-wide field scanning laser
      ophthalmoscopy.
AB  - Features of the retinal vasculature, such as vessel widths, are considered
      biomarkers for systemic disease. The aim of this work is to present a supervised
      approach to vessel segmentation in ultra-wide field of view scanning laser
      ophthalmoscope (UWFoV SLO) images and to evaluate its performance in terms of
      segmentation and vessel width estimation accuracy. The results of the proposed
      method are compared with ground truth measurements from human observers and with
      existing state-of-the-art techniques developed for fundus camera images that we
      optimized for UWFoV SLO images. Our algorithm is based on multi-scale matched
      filters, a neural network classifier and hysteresis thresholding. After spline
      based refinement of the detected vessel contours, the vessel widths are estimated
      from the binary maps. Such analysis is performed on SLO images for the first
      time. The proposed method achieves the best results, both in vessel segmentation
      and in width estimation, in comparison to other automatic techniques. 

PMID- 25574442
TI  - Monte Carlo modeling of angiographic optical coherence tomography.
AB  - Optical coherence tomography (OCT) provides both structural and angiographic
      imaging modes. Because of its unique capabilities, OCT-based angiography has been
      increasingly adopted into small animal and human subject imaging. To support the
      development of the signal and image processing algorithms on which OCT-based
      angiography depends, we describe here a Monte Carlo-based model of the imaging
      approach. The model supports arbitrary three-dimensional vascular network
      geometries and incorporates methods to simulate OCT signal temporal
      decorrelation. With this model, it will be easier to compare the performance of
      existing and new angiographic signal processing algorithms, and to quantify the
      accuracy of vascular segmentation algorithms. The quantitative analysis of key
      algorithms within OCT-based angiography may, in turn, simplify the selection of
      algorithms in instrument design and accelerate the pace of new algorithm
      development. 

PMID- 25574443
TI  - Miniature objective lens with variable focus for confocal endomicroscopy.
AB  - Spectrally encoded confocal microscopy (SECM) is a reflectance confocal
      microscopy technology that can rapidly image large areas of luminal organs at
      microscopic resolution. One of the main challenges for large-area SECM imaging in
      vivo is maintaining the same imaging depth within the tissue when patient motion
      and tissue surface irregularity are present. In this paper, we report the
      development of a miniature vari-focal objective lens that can be used in an SECM
      endoscopic probe to conduct adaptive focusing and to maintain the same imaging
      depth during in vivo imaging. The vari-focal objective lens is composed of an
      aspheric singlet with an NA of 0.5, a miniature water chamber, and a thin elastic
      membrane. The water volume within the chamber was changed to control curvature of
      the elastic membrane, which subsequently altered the position of the SECM focus.
      The vari-focal objective lens has a diameter of 5 mm and thickness of 4 mm. A
      vari-focal range of 240 MUm was achieved while maintaining lateral resolution
      better than 2.6 MUm and axial resolution better than 26 MUm. Volumetric SECM
      images of swine esophageal tissues were obtained over the vari-focal range of 260
      MUm. SECM images clearly visualized cellular features of the swine esophagus at
      all focal depths, including basal cell nuclei, papillae, and lamina propria. 

PMID- 25574444
TI  - Fast monitoring of in-vivo conformational changes in myosin using single scan
      polarization-SHG microscopy.
AB  - Fast imaging of molecular changes under high-resolution and label-free conditions
      are essential for understanding in-vivo processes, however, current techniques
      are not able to monitor such changes in real time. Polarization sensitive second
      harmonic generation (PSHG) imaging is a minimally invasive optical microscopy
      technique capable of quantifying molecular conformational changes occurring below
      the diffraction limit. Up to now, such information is generally retrieved by
      exciting the sample with different linear polarizations. This procedure requires
      the sample to remain static during measurements (from a few second to minutes),
      preventing the use of PSHG microscopy from studying moving samples or molecular
      dynamics in living organisms. Here we demonstrate an imaging method that is one
      order of magnitude faster than conventional PSHG. Based on circular polarization
      excitation and instantaneous polarimetry analysis of the second harmonic signal
      generated in the tissue, the method is able to instantaneously obtain molecular
      information within a pixel dwell time. As a consequence, a single scan is only
      required to retrieve all the information. This allowed us to perform PSHG imaging
      in moving C. elegans, monitoring myosin's dynamics during the muscular
      contraction and relaxation. Since the method provides images of the molecular
      state, an unprecedented global understanding of the muscles dynamics is possible
      by correlating changes in different regions of the sample. 

PMID- 25574445
TI  - Measurement of a multi-layered tear film phantom using optical coherence
      tomography and statistical decision theory.
AB  - To extend our understanding of tear film dynamics for the management of dry eye
      disease, we propose a method to optically sense the tear film and estimate
      simultaneously the thicknesses of the lipid and aqueous layers. The proposed
      method, SDT-OCT, combines ultra-high axial resolution optical coherence
      tomography (OCT) and a robust estimator based on statistical decision theory
      (SDT) to achieve thickness measurements at the nanometer scale. Unlike
      conventional Fourier-domain OCT where peak detection of layers occurs in Fourier
      space, in SDT-OCT thickness is estimated using statistical decision theory
      directly on the raw spectra acquired with the OCT system. In this paper, we
      demonstrate in simulation that a customized OCT system tailored to ~1 um axial
      point spread function (FWHM) in the corneal tissue, combined with the maximum
      likelihood estimator, can estimate thicknesses of the nanometer-scale lipid and
      micron-scale aqueous layers of the tear film, simultaneously, with nanometer
      precision. This capability was validated in experiments using a physical phantom
      that consists of two layers of optical coatings that mimic the lipid and aqueous
      layers of the tear film. 

PMID- 25574447
TI  - Evaluation of flow velocities after carotid artery stenting through split
      spectrum Doppler optical coherence tomography and computational fluid dynamics
      modeling.
AB  - Hemodynamics plays a critical role in the development of atherosclerosis,
      specifically in regions of curved vasculature such as bifurcations exhibiting
      irregular blood flow profiles. Carotid atherosclerotic disease can be intervened
      by stent implantation, but this may result in greater alterations to local blood
      flow and consequently further complications. This study demonstrates the use of a
      variant of Doppler optical coherence tomography (DOCT) known as split spectrum
      DOCT (ssDOCT) to evaluate hemodynamic patterns both before and after stent
      implantation in the bifurcation junction in the internal carotid artery (ICA).
      Computational fluid dynamics (CFD) models were constructed to simulate blood
      velocity profiles and compared to the findings achieved through ssDOCT images.
      Both methods demonstrated noticeable alterations in hemodynamic patterns
      following stent implantation, with features such as slow velocity regions at the
      neck of the bifurcation and recirculation zones at the stent struts. Strong
      correlation between CFD models and ssDOCT images demonstrate the potential of
      ssDOCT imaging in the optimization of stent implantation in the clinical setting.

PMID- 25574448
TI  - Engineering optically triggered droplets for photoacoustic imaging and therapy.
AB  - Liquid perfluorocarbon (PFC) droplets incorporating optical absorbers can be
      vaporized through photothermal heating using a pulsed laser source. Here, we
      report on the effect of droplet core material on the optical fluence required to
      produce droplet vaporization. We fabricate gold nanoparticle templated
      microbubbles filled with various PFC gases (C3F8, C4F10, and C5F12) and apply
      pressure to condense them into droplets. The core material is found to have a
      strong effect on the threshold optical fluence, with lower boiling point droplets
      allowing for vaporization at lower laser fluence. The impact of droplet size on
      vaporization threshold is discussed, as well as a proposed mechanism for the
      relatively broad distribution of vaporization thresholds observed within a
      droplet population with the same core material. We propose that the control of
      optical vaporization threshold enabled by engineering the droplet core may find
      application in contrast enhanced photoacoustic imaging and therapy. 

PMID- 25574446
TI  - Ultrahigh speed endoscopic optical coherence tomography for gastroenterology.
AB  - We describe an ultrahigh speed endoscopic swept source optical coherence
      tomography (OCT) system for clinical gastroenterology using a vertical-cavity
      surface-emitting laser (VCSEL) and micromotor imaging catheter. The system had a
      600 kHz axial scan rate and 8 um axial resolution in tissue. Imaging was
      performed with a 3.2 mm diameter imaging catheter at 400 frames per second with a
      12 um spot size. Three-dimensional OCT (3D-OCT) imaging was performed in patients
      with a cross section of pathologies undergoing upper and lower endoscopy. The use
      of distally actuated imaging catheters enabled OCT imaging with more flexibility,
      such as volumetric imaging in the small intestine and the assessment of hiatal
      hernia using retroflex imaging. The high rotational scanning stability of the
      micromotor enabled 3D volumetric imaging with micron scale volumetric accuracy
      for both en face OCT and cross-sectional imaging, as well as OCT angiography
      (OCTA) for 3D visualization of subsurface microvasculature. The ability to
      perform both structural and functional 3D OCT imaging in the GI tract with
      microscopic accuracy should enable a wide range of studies and enhance the
      sensitivity and specificity of OCT for detecting pathology. 

PMID- 25574450
TI  - Facing Imbalanced Data Recommendations for the Use of Performance Metrics.
AB  - Recognizing facial action units (AUs) is important for situation analysis and
      automated video annotation. Previous work has emphasized face tracking and
      registration and the choice of features classifiers. Relatively neglected is the
      effect of imbalanced data for action unit detection. While the machine learning
      community has become aware of the problem of skewed data for training
      classifiers, little attention has been paid to how skew may bias performance
      metrics. To address this question, we conducted experiments using both simulated
      classifiers and three major databases that differ in size, type of FACS coding,
      and degree of skew. We evaluated influence of skew on both threshold metrics
      (Accuracy, F-score, Cohen's kappa, and Krippendorf's alpha) and rank metrics
      (area under the receiver operating characteristic (ROC) curve and precision
      recall curve). With exception of area under the ROC curve, all were attenuated by
      skewed distributions, in many cases, dramatically so. While ROC was unaffected by
      skew, precision-recall curves suggest that ROC may mask poor performance. Our
      findings suggest that skew is a critical factor in evaluating performance
      metrics. To avoid or minimize skew-biased estimates of performance, we recommend
      reporting skew-normalized scores along with the obtained ones.

PMID- 25574449
TI  - Digitally synthesized beat frequency-multiplexed fluorescence lifetime
      spectroscopy.
AB  - Frequency domain fluorescence lifetime imaging is a powerful technique that
      enables the observation of subtle changes in the molecular environment of a
      fluorescent probe. This technique works by measuring the phase delay between the
      optical emission and excitation of fluorophores as a function of modulation
      frequency. However, high-resolution measurements are time consuming, as the
      excitation modulation frequency must be swept, and faster low-resolution
      measurements at a single frequency are prone to large errors. Here, we present a
      low cost optical system for applications in real-time confocal lifetime imaging,
      which measures the phase vs. frequency spectrum without sweeping. Deemed Lifetime
      Imaging using Frequency-multiplexed Excitation (LIFE), this technique uses a
      digitally-synthesized radio frequency comb to drive an acousto-optic deflector,
      operated in a cat's-eye configuration, to produce a single laser excitation beam
      modulated at multiple beat frequencies. We demonstrate simultaneous fluorescence
      lifetime measurements at 10 frequencies over a bandwidth of 48 MHz, enabling high
      speed frequency domain lifetime analysis of single- and multi-component sample
      mixtures. 

PMID- 25574451
TI  - Child and Parent Perceptions of Interparental Relationship Conflict Predict
      Preschool Children's Adjustment.
AB  - Interparental relationship conflict has consistently been linked to child
      adjustment problems, with children's perceptions of such conflict particularly
      predictive of their outcomes. Despite mounting evidence that preschool children
      can provide reliable and valid accounts of family functioning, little research
      has examined preschool children's perceptions of interparental conflict. The
      present study employed a multi-informant design for both reports of interparental
      conflict (preschool children and their mothers and fathers) and reports of child
      adjustment (preschool children, their mothers and fathers, and their preschool
      teachers). Children completed pictorial measures of interparental conflict and of
      self-esteem that paralleled questionnaires completed by adult respondents. For
      both child behavior problems and child self-esteem, preschool children's
      perceptions of interparental conflict predicted their adjustment. Preschool
      children's reports of interparental conflict were significantly associated with
      their self-esteem and with both parents' and teachers' reports of child behavior
      problems, and this association remained significant when controlling for parents'
      reports of interparental conflict. Further, the interaction between parents'
      reports and children's reports of interparental conflict added unique variance to
      the prediction of preschool teachers' reports of children's behavior problems.

PMID- 25574452
TI  - Changing the Food Environment for Obesity Prevention: Key Gaps and Future
      Directions.
AB  - The food environment has a great impact on the nutritional health of the
      population. Food environment interventions have become a popular strategy to
      address the obesity epidemic. However, there are still significant gaps in our
      understanding of the most effective strategies to modify the food environment to
      improve health. In this review, we examine key gaps in the food environment
      intervention literature, including the need for: developing appropriate formative
      research plans when addressing the food environment; methods for selecting
      intervention domains and components; incorporating food producers and
      distributors in intervention strategies; strengthening evaluation of
      environmental interventions; building the evidence base for food environment
      interventions in diverse settings; engaging policy makers in the process of
      modifying the food environment; and creating systems science models to examine
      the costs and benefits of a potential program or policy on the food environment
      prior to implementation. In addition, we outline the need for strategies for
      addressing these issues including conducting additional pilot interventions,
      developing additional methodologies, and embracing the use of simulation models. 

PMID- 25574454
TI  - Factor Structure of Scores from the Conners' Rating Scales-Revised Among Nepali
      Children.
AB  - This study used exploratory and confirmatory factor analyses to examine the
      structures of scores from the Conners' Teacher and Parent Rating Scales-Revised
      (CTRS-R and CPRS-R, respectively; Conners, 1997). The scales were administered to
      1,835 parents and 1,387 teachers of children in Nepal's Sarlahi district - a
      region where no other measures of child psychopathology have been studied. With a
      Nepali sample, the findings indicate that reduced two factor models for the
      Conners' scales are superior to the models identified in the scale development
      research. The hyperactivity and inattention factors were comparable to what has
      been identified in prior research, while other factors (e.g., social problems)
      differed substantially. Implications for use of the Conners' scales in Nepal and
      cross cultural issues in the assessment of ADHD symptoms are discussed.

PMID- 25574455
TI  - Monotone Confounding, Monotone Treatment Selection and Monotone Treatment
      Response.
AB  - Manski (1997) and Manski and Pepper (2000) gave sharp bounds on causal effects
      under the assumptions of monotone treatment response (MTR) and monotone treatment
      selection (MTS). VanderWeele (2008) provided bounds for binary treatment under an
      assumption of monotone confounding (MC). We discuss the relation between MC and
      MTS and provide bounds under various combinations of these assumptions. We show
      that MC and MTS coincide for a binary treatment, but MC does not imply MTS for a
      treatment variable with more than two levels.

PMID- 25574453
TI  - Recent Advances in Understanding of NASH: MicroRNAs as Both Biochemical Markers
      and Players.
AB  - Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatis (NASH)
      are becoming the dominant liver diseases in the US and Western World. Extensive
      work is being done to diagnose, understand, and explore the pathogenesis of these
      multivariable complex diseases. Recently a new avenue of biologic regulation is
      being explored. MicroRNAs are non-coding RNAs that modulate the expression of
      multiple genes and have been implicated in multiple diseases. Recently there is a
      growing body of evidence supporting a significant role of microRNAs in NAFLD
      pathogenesis and progression to NASH, and hinting at their use as targets,
      biomarkers and potential therapeutic tools. This review is designed to highlight
      some of the recent work on a few of the key microRNAs involved in the
      pathogenesis of NAFLD and NASH.

PMID- 25574456
TI  - Prevalence of Childhood Obsessive-Compulsive Personality Traits in Adults with
      Obsessive Compulsive Disorder versus Obsessive Compulsive Personality Disorder.
AB  - Identifying risk factors of psychopathology has been an important research
      challenge. Prior studies examining the impact of childhood temperament on adult
      disorder have largely focused on undercontrolled and inhibited presentations,
      with little study of overcontrolled traits such as obsessive-compulsive
      personality traits (OCPTs). We compared rates of childhood OCPTs in adults with
      OCD (without OCPD) (n = 28) to adults with OCPD (without OCD) (n = 27), adults
      with both OCD and OCPD (n = 28), and healthy controls (HC) (n= 28), using the
      Childhood Retrospective Perfectionism Questionnaire, a validated measure of
      perfectionism, inflexibility, and drive for order. Adults with OCPD (both with
      and without comorbid OCD) reported higher rates of all three childhood OCPTs
      relative to HC. Individuals with OCD (without OCPD) reported higher rates of
      inflexibility and drive for order relative to HC, suggesting that these traits
      may presage the development of OCD, independent of OCPD. Childhood OCPTs were
      associated with particular OCD symptom dimensions in adulthood
      (contamination/cleaning, doubt/checking, and symmetry/ordering), independent of
      OCD onset age and OCPD diagnosis. Longitudinal prospective studies evaluating
      OCPTs in children are needed to better understand the progression of these traits
      from childhood to adulthood and their ability to predict future psychopathology.

PMID- 25574458
TI  - Extract of Artemisia lavandulaefolia Inhibits In Vitro Angiogenesis in Human
      Umbilical Vein Endothelial Cells.
AB  - Angiogenesis is important processes for tumor growth and metastasis. Anti
      angiogenesis target therapy has recently been known to be new anti-cancer
      therapeutic strategies. Natural products such as traditional medicine comprise a
      major source of angiogenesis inhibitors. Artemisia lavandulaefolia has been known
      to use in the traditional medical practices. However, its molecular mechanism on
      the tumor protection and therapy was not clearly elucidated. In this study, we
      investigated the possibility that extract of A. lavandulaefolia inhibits in vitro
      angiogenesis. Therefore, we examined the effect of extract of A. lavandulaefolia
      on the vascular network formation of human umbilical vein endothelial cells
      (HUVECs). We found that the treatment of A. lavandulaefolia extract suppressed
      the tube formation of HUVECs without any influence on the viability of HUVECs. In
      addition, extract of A. lavandulaefolia inhibited the migration and invasion of
      HUVECs. These results suggest that extract of A. lavandulaefolia could be act for
      an angiogenic inhibitor. 

PMID- 25574457
TI  - Effects of developmental manganese, stress, and the combination of both on
      monoamines, growth, and corticosterone.
AB  - Developmental exposure to manganese (Mn) or stress can each be detrimental to
      brain development. Here, Sprague-Dawley rats were exposed to two housing
      conditions and Mn from postnatal day (P)4-28. Within each litter two males and 2
      females were assigned to the following groups: 0 (vehicle), 50, or 100 mg/kg Mn
      by oral gavage every other day. Half the litters were reared in cages with
      standard bedding and half with no bedding. One pair/group in each litter had an
      acute shallow water stressor before tissue collection (i.e., standing in shallow
      water). Separate litters were assessed at P11, 19, or 29. Mn-treated rats raised
      in standard cages showed no change in baseline corticosterone but following acute
      stress increased more than controls on P19; no Mn effects were seen on P11 or
      P29. Mn increased neostriatal dopamine in females at P19 and norepinephrine at
      P11 and P29. Mn increased hippocampal dopamine at P11 and P29 and 5-HT at P29
      regardless of housing or sex. Mn had no effect on hypothalamic dopamine, but
      increased norepinephrine in males at P29 and 5-HT in males at all ages
      irrespective of rearing condition. Barren reared rats showed no or opposite
      effects of Mn, i.e., barren rearing + Mn attenuated corticosterone increases to
      acute stress. Barren rearing also altered the Mn-induced changes in dopamine and
      norepinephrine in the neostriatum, but not in the hippocampus. Barren rearing
      caused a Mn-associated increase in hypothalamic dopamine at P19 and P29 not seen
      in standard reared Mn-treated groups. Developmental Mn alters monoamines and
      corticosterone as a function of age, stress (acute and chronic), and sex.

PMID- 25574459
TI  - Cancer Preventive Potential of Kimchi Lactic Acid Bacteria (Weissella cibaria,
      Lactobacillus plantarum).
AB  - The number of death due to cancer has been increasing in Korea. Chemotherapy is
      known to cause side effects because it damages not only cancerous cells but
      healthy cells. Recently, attention has focused on food-derived chemopreventive
      and anti-tumor agents or formulations with fewer side effects. Kimchi, most
      popular and widely consumed in Korea, contains high levels of lactic acid
      bacteria and has been shown to possess chemopreventive effects. This review
      focuses on Weissella cibaria and Lactobacillus plantarum, the representatives of
      kimchi lactic acid bacteria, in terms of their abilities to prevent cancer.
      Further studies are needed to understand the mechanisms by which lactic acid
      bacteria in kimchi prevent carcinogenic processes and improve immune functions. 

PMID- 25574460
TI  - Helicobacter pylori Induces Hypermethylation of CpG Islands Through Upregulation
      of DNA Methyltransferase: Possible Involvement of Reactive Oxygen/Nitrogen
      Species.
AB  - Helicobacter pylori infection has been considered to be one of the major factors
      implicated in etiology of gastric cancer. Aberrant DNA methylation accounts for
      epigenetic modifications induced by H. pylori. H. pylori-induced hypermethylation
      has been linked to enhancement of the rates of metastasis and recurrence in
      gastric cancer patients. H. pylori-induced gene hypermethylation has been known
      to be associated with inflammation. However, the molecular mechanisms underlying
      H. pylori-induced hypermethylation remain largely unknown. This review highlights
      possible involvement of reactive oxygen/nitrogen species in H. pylori-induced
      hypermethylation and gastric carcinogenesis. 

PMID- 25574461
TI  - Pycnogenol Induces Nuclear Translocation of Apoptosis-inducing Factor and Caspase
      independent Apoptosis in MC-3 Human Mucoepidermoid Carcinoma Cell Line.
AB  - BACKGROUND: Pycnogenol is extracted from the pine bark of a tree known as Pinus
      pinaster that has variety biological effects. However, its anticancer activity
      has not yet been completely studied. The aim of this study is to investigate
      anticancer effect of pycnogenol in MC-3 human mucoepidermoid carcinoma (MEC) cell
      line. METHODS: We describe the effect of anti-cancer of pycnogenol in MC-3 human
      oral MEC cells using trypan blue exclusion assay, 3-(4,5-dimethylthiazol-2-yl)-(3
      carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) assay, Western
      blot, preparation of cytosolic and nuclear fractions, immunocytochemistry and
      reverse transcriptase polymerase chain reaction. RESULTS: Pycnogenol
      significantly decreased cell viability and also induced caspase-independent
      apoptosis. We confirmed that pycnogenol induced the translocation of apoptosis
      inducing factor into nucleus and regulated apoptosis. Also, Bak protein stability
      was partly enhanced by pycnogenol to elevate the expression level of Bak protein.
      CONCLUSIONS: Overall, pycnogenol may be a fascinating therapeutic drug candidate
      for the treatment of MEC.

PMID- 25574462
TI  - Induction of Cell Cycle Arrest and Apoptosis by Physcion, an Anthraquinone
      Isolated From Rhubarb (Rhizomes of Rheum tanguticum), in MDA-MB-231 Human Breast
      Cancer Cells.
AB  - BACKGROUND: Physcion is an anthraquinone from rhubarb (rhizomes of Rheum
      tanguticum) and has been reported to have anti-inflammatory, hepatoprotective,
      antifungal, and anti-cancer activities. However, the growth inhibitory activity
      against human cancer cells and the underlying molecular mechanisms have been
      poorly determined. This study was designed to investigate the anti-proliferative
      activity of physcion by induction of cell cycle arrest and apoptosis in human MDA
      MB-231 triple negative breast cancer cell line. METHODS: MDA-MB-231 cells were
      treated with physcion, and the anti-proliferative activity was evaluated by the
      sulforhodamine B assay. The mechanisms of action for the growth inhibitory
      activity of physcion were evaluated by flow cytometry for cell cycle
      distribution, and by Western blot for the assessment of potential target
      proteins. RESULTS: Physcion showed a significant anti-proliferative activity
      against MDA-MB-231 human breast cancer cells. Flow cytometric analysis indicated
      that physcion markedly induced the accumulation of cells in the G0/G1 phase and
      the increase of cell population in the sub-G1 phase. The G0/G1 cell cycle arrest
      by physcion was associated with the down-regulation of Cyclin D1, Cyclin A, CDK4,
      CDK2, c-Myc and phosphorylated Rb protein expressions. The increase of sub-G1
      peak by physcion was closely correlated with the induction of apoptosis, which
      was confirmed by the induction of cleaved poly-(adenosine diphosphate ribose)
      polymerase, activation of Caspases, and suppression of Bid and Bcl-2 expression.
      CONCLUSIONS: The induction of G0/G1 cell cycle arrest and apoptosis might be one
      of the plausible mechanisms of actions for the anti-proliferative activity of
      physcion in human breast cancer cells.

PMID- 25574463
TI  - Anti-inflammatory Effects of Schisandra chinensis (Turcz.) Baill Fruit Through
      the Inactivation of Nuclear Factor-kappaB and Mitogen-activated Protein Kinases
      Signaling Pathways in Lipopolysaccharide-stimulated Murine Macrophages.
AB  - BACKGROUND: Schisandrae Fructus, the dried fruit of Schisandra chinensis (Turcz.)
      Baill. (Magnoliaceae), is widely used in traditional medicine for the treatment
      of a number of chronic inflammatory diseases. This study examined the anti
      inflammatory effects of Schisandrae Fructus ethanol extract (SF) on the
      production of pro-inflammatory substances in lipopolysaccharide (LPS)-stimulated
      RAW 264.7 macrophages. METHODS: To measure the effects of SF on pro-inflammatory
      mediator and inflammatory cytokine's expression and production in RAW 264.7
      cells, we used the following methods: cell viability assay, Griess reagent assay,
      enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain
      reaction, Western blotting analysis and immunofluorescence staining. RESULTS:
      Stimulation of the RAW 264.7 cells with LPS caused an elevated production of
      nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)
      1beta, which was markedly inhibited by the pretreatment with SF without causing
      any cytotoxic effects. SF also inhibited the expression of inducible NO synthase,
      TNF-alpha, and IL-1beta protein and their mRNAs in LPS-stimulated RAW 264.7
      cells. Furthermore, SF attenuated LPS-induced nuclear translocation of nuclear
      factor-kappaB (NF-kappaB) by reducing inhibitory-kappaB degradation, and reduced
      the phosphorylation of mitogen-activated protein kinases (MAPKs), implying that
      SF regulated LPS-induced NF-kappaB-dependent inflammatory pathways through
      suppression of MAPKs activation. CONCLUSIONS: SF may be useful for the treatment
      of various inflammatory diseases.

PMID- 25574464
TI  - Eugenol-rich Fraction of Syzygium aromaticum (Clove) Reverses Biochemical and
      Histopathological Changes in Liver Cirrhosis and Inhibits Hepatic Cell
      Proliferation.
AB  - BACKGROUND: Dried flower bud of Syzygium aromaticum (clove) is rich in eugenol,
      an antioxidant and antiinflammatory compound that can protect liver against
      injury. Clove, besides eugenol, also contains other pharmacologically active
      phytochemicals such as beta-sitosterol and ascorbic acid. This study reports the
      effect of eugenol-rich fraction (ERF) of clove on liver cirrhosis induced by
      thioacetamide. METHODS: Cirrhosis of the liver, which predisposes to
      hepatocellular carcinoma, was induced by administering thioacetamide (0.03%) in
      drinking water for 16 weeks. Cirrhotic animals were divided into two groups; the
      treated group was administered ERF for 9 weeks, one week after discontinuation of
      thioacetamide, while the other group received normal saline for a similar
      duration of time. RESULTS: The treatment with ERF, as determined by
      histopathology and through a battery of biochemical markers of hepatic injury,
      oxidative stress and drug metabolizing enzymes, significantly ameliorated the
      signs of liver cirrhosis. It lowered the elevated levels of alkaline phosphatase,
      gamma-glutamyl transferase and other biochemical changes in liver cirrhosis.
      Histopathology of the liver corroborated the effect of ERF with biochemical
      findings. ERF treatment further inhibited cell proliferation, as demonstrated by
      reduced [(3)H]-thymidine uptake. CONCLUSIONS: Data provide evidence supporting
      the protective action of ERF on liver cirrhosis. The study assumes significance
      because cirrhosis predisposes the liver to cancer, which is characterized by
      abnormal cell proliferation. ERF in this study is reported to inhibit hepatic
      cell proliferation and at the same time decrease oxidative stress, which might be
      the mechanism of protection against liver cirrhosis.

PMID- 25574465
TI  - Aging alters hepatic DNA hydroxymethylation, as measured by liquid
      chromatography/mass spectrometry.
AB  - BACKGROUND: Aging is one of the most important risk factors for cancer. It
      appears that aberrant epigenetic changes might be a common driver of aging and
      cancer. Among them are changes in DNA methylation and DNA hydroxymethylation. The
      5' carbon of cytosines in CpG dinucleotides of DNA can be either methylated or
      hydroxymethylated. Like 5'-methylcytosine, changes in 5'-hydroxymethylcytosine
      may occur due to aging, potentially leading to downstream changes in
      transcription and cancer development. METHODS: We set up a method to measure 5'
      methyl-2'-deoxycytidine and 5'-hydroxymethyl-2'-deoxycytidine in DNA using liquid
      chromatography/mass spectrometry (LC/MS-MS) and used this method to measure the
      percentage of total cytosine that was either methylated or hydroxymethylated in
      the liver tissues of young and old C57Bl/6 male mice. The DNA was enzymatically
      hydrolyzed by sequential digestion with nuclease P1, phosphodiesterase I and
      alkaline phosphatase. The isotopomers [(15)N3]-2'-deoxycytidine and (methyl-d 3,
      ring-6-d 1)-5-methyl-2'-deoxycytidine were added to the DNA hydrolysates as
      internal standards. DNA methylation and hydroxymethylation were calculated as a
      percentage of total deoxycytidine in genomic DNA. RESULTS: Within day variations
      for DNA methylation and hydroxymethylation were 3.45% and 8.40%, while day to day
      variations were 6.14% and 17.68%, respectively. Using this method it was
      determined that hepatic DNA of old mice had increased levels of
      hydroxymethylation relative to young (0.32 +/- 0.02% vs. 0.24 +/- 0.01%, P =
      0.02), with no significant changes in 5'-methylcytosine. CONCLUSIONS: DNA
      hydroxymethylation measured by LC/MS-MS method can be a novel biomarker of aging.
      It will be useful to investigate the potential role of DNA hydroxymethylation in
      the development and prevention of age-associated cancer.

PMID- 25574466
TI  - The diagnostic validity of the (13)c-urea breath test in the gastrectomized
      patients: single tertiary center retrospective cohort study.
AB  - BACKGROUND: This study was conducted to evaluate the diagnostic validity of the
      (13)C-urea breath test ((13)C-UBT) in the remnant stomach after partial
      gastrectomy for gastric cancer. METHODS: The (13)C-UBT results after Helicobacter
      pylori eradication therapy was compared with the results of endoscopic biopsy
      based methods in the patients who have received partial gastrectomy for the
      gastric cancer. RESULTS: Among the gastrectomized patients who showed the
      positive (13)C-UBT results (>= 2.50/00, n = 47) and negative (13)C-UBT results (<
      2.50/00, n = 114) after H. pylori eradication, 26 patients (16.1%) and 4 patients
      (2.5%) were found to show false positive and false negative results based on
      biopsy-based methods, respectively. The sensitivity, specificity, false positive
      rate, and false negative rate for the cut-off value of 2.50/00 were 84.0%, 80.9%,
      19.1%, and 16.0%, respectively. The positive and negative predictive values were
      44.7% and 96.5%, respectively. In the multivariate analysis, two or more H.
      pylori eradication therapies (odds ratio = 3.248, 95% confidence interval= 1.088
      9.695, P = 0.035) was associated with a false positive result of the (13)C-UBT.
      CONCLUSIONS: After partial gastrectomy, a discordant result was shown in the
      positive (13)C-UBT results compared to the endoscopic biopsy methods for
      confirming the H. pylori status after eradication. Additional endoscopic biopsy
      based H. pylori tests would be helpful to avoid unnecessary treatment for H.
      pylori eradication in these cases.

PMID- 25574467
TI  - Increased serum levels of inflammatory mediators and low frequency of regulatory
      T cells in the peripheral blood of preeclamptic Mexican women.
AB  - Regulatory T cells (T(regs); CD4+CD25(high)Foxp3+) are critical in maintaining
      immune tolerance during pregnancy and uterine vascularization. In this study, we
      show that, in Mexican women with different preeclamptic severity levels, the
      number of T(regs) and the subset of CD4+CD25(high)Foxp3+ are decreased compared
      with those of normotensive pregnant women (NP). Moreover, a systemic inflammatory
      state is a pivotal feature in the pathogenesis of this disorder and could be
      related to hypertension and endothelial dysfunction. Likewise, we observed
      elevated levels of IL-6, TNF-alpha, and IL-8 in the serum of severe preeclamptic
      patients (SPE); no differences were found in the IL-1beta and IL-10 levels
      compared with those of NP patients. An analysis of chemokines in the preeclamptic
      serum samples showed high levels of CXCL10, CCL2, and CXCL9. Our findings suggest
      that the preeclamptic state is linked with systemic inflammation and reduced
      numbers of T(regs).

PMID- 25574468
TI  - Hypoglossal-facial nerve reconstruction using a Y-tube-conduit reduces aberrant
      synkinetic movements of the orbicularis oculi and vibrissal muscles in rats.
AB  - The facial nerve is the most frequently damaged nerve in head and neck trauma.
      Patients undergoing facial nerve reconstruction often complain about disturbing
      abnormal synkinetic movements of the facial muscles (mass movements, synkinesis)
      which are thought to result from misguided collateral branching of regenerating
      motor axons and reinnervation of inappropriate muscles. Here, we examined whether
      use of an aorta Y-tube conduit during reconstructive surgery after facial nerve
      injury reduces synkinesis of orbicularis oris (blink reflex) and vibrissal
      (whisking) musculature. The abdominal aorta plus its bifurcation was harvested (N
      = 12) for Y-tube conduits. Animal groups comprised intact animals (Group 1),
      those receiving hypoglossal-facial nerve end-to-end coaptation alone (HFA; Group
      2), and those receiving hypoglossal-facial nerve reconstruction using a Y-tube
      (HFA-Y-tube, Group 3). Videotape motion analysis at 4 months showed that HFA-Y
      tube group showed a reduced synkinesis of eyelid and whisker movements compared
      to HFA alone. 

PMID- 25574469
TI  - Treatment for intramuscular lipoma frequently confused with sarcoma: a 6-year
      restrospective study and literature review.
AB  - INTRODUCTION: Intramuscular lipoma is a very rare form of lipoma, known to be
      categorized as an infiltrating lipoma due to its tendencies to infiltrate the
      muscle or the synovium. Contrary to other subcutaneous lipomas, even after
      surgical removal, the rate of local recurrence ranges at a high rate from 50~80%
      and differential diagnosis with liposarcoma is very difficult. PATIENTS AND
      METHODS: A retrospective chart review was conducted for a total of 27 patients.
      Before performing a surgery based on the types of mass, a radiologic imaging
      study was performed. An intraoperative frozen biopsy was performed on every
      patient and the results were compared. The progress was monitored every 3 to 6
      months for recurrence or struggles with rehabilitation. RESULTS: There were 13
      male and 14 female patients with an average age of 54.6. The average tumor size
      was 8.2 cm (1.1 cm~31.6 cm). Excision was performed using a wide excision. All 27
      individuals were initially diagnosed as intramuscular lipoma; however, 1 of the
      patients was rediagnosed as liposarcoma in the final checkup. The patients had an
      average of 3 years and 1 month of follow-up and did not suffer recurrences.
      CONCLUSION: Thus, it is essential that a frozen biopsy is performed during the
      surgery in order to identify its malignancy. And a wide excision like malignant
      tumor operation is a principle of treatment.

PMID- 25574470
TI  - Highlight on advances in nontuberculous mycobacterial disease in North America.
AB  - Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and exist as
      an important cause of pulmonary infections in humans. Pulmonary involvement is
      the most common disease manifestation of NTM and the incidence of NTM is growing
      in North America. Susceptibility to NTM infection is incompletely understood;
      therefore preventative tools are not well defined. Treatment of pulmonary
      nontuberculous mycobacterial (NTM) infection is difficult and entails multiple
      antibiotics and an extended treatment course. Also, there is a considerable
      variation in treatment management that should be considered before initiating
      treatment. We highlight the new findings in the epidemiology diagnosis and
      treatment of mycobacterial infections. We debate new advances regarding NTM
      infection in cystic fibrosis patients and solid organ transplant recipients.
      Finally, we introduce a new epidemiologic model for NTM disease based on
      virulence-exposure-host factors. 

PMID- 25574472
TI  - Endogenous cerebellar neurogenesis in adult mice with progressive ataxia.
AB  - OBJECTIVE: Transplanting exogenous neuronal progenitors to replace damaged
      neurons in the adult brain following injury or neurodegenerative disorders and
      achieve functional amelioration is a realistic goal. However, studies so far have
      rarely taken into consideration the preexisting inflammation triggered by the
      disease process that could hamper the effectiveness of transplanted cells. Here,
      we examined the fate and long-term consequences of human cerebellar granule
      neuron precursors (GNP) transplanted into the cerebellum of Harlequin mice, an
      adult model of progressive cerebellar degeneration with early-onset microgliosis.
      METHODS: Human embryonic stem cell-derived progenitors expressing Atoh1, a
      transcription factor key to GNP specification, were generated in vitro and
      stereotaxically transplanted into the cerebellum of preataxic Harlequin mice. The
      histological and functional impact of these transplants was followed using
      immunolabeling and Rotarod analysis. RESULTS: Although transplanted GNPs did not
      survive beyond a few weeks, they triggered the proliferation of endogenous nestin
      positive precursors in the leptomeninges that crossed the molecular layer and
      differentiated into mature neurons. These phenomena were accompanied by the
      preservation of the granule and Purkinje cell layers and delayed ataxic changes.
      In vitro neurosphere generation confirmed the enhanced neurogenic potential of
      the cerebellar leptomeninges of Harlequin mice transplanted with exogenous GNPs.
      INTERPRETATION: The cerebellar leptomeninges of adult mice contain an endogenous
      neurogenic niche that can be stimulated to yield mature neurons from an as-yet
      unidentified population of progenitors. The transplantation of human GNPs not
      only stimulates this neurogenesis, but, despite the potentially hostile
      environment, leads to neuroprotection and functional amelioration.

PMID- 25574471
TI  - Lactoferrin during lactation protects the immature hypoxic-ischemic rat brain.
AB  - OBJECTIVE: Lactoferrin (Lf) is an iron-binding glycoprotein secreted in maternal
      milk presenting anti-inflammatory and antioxidant properties. It shows efficient
      absorption into the brain from nutritional source. Brain injury frequently
      resulting from cerebral hypoxia-ischemia (HI) has a high incidence in premature
      infants with ensuing neurodevelopmental disabilities. We investigated the
      neuroprotective effect of maternal nutritional supplementation with Lf during
      lactation in a rat model of preterm HI brain injury using magnetic resonance
      imaging (MRI), brain gene, and protein expression. METHODS: Moderate brain HI was
      induced using unilateral common carotid artery occlusion combined with hypoxia
      (6%, 30 min) in the postnatal day 3 (P3) rat brain (24-28 weeks human
      equivalent). High-field multimodal MRI techniques were used to investigate the
      effect of maternal Lf supplementation through lactation. Expression of cytokine
      coding genes (TNF-alpha and IL-6), the prosurvival/antiapoptotic AKT protein and
      caspase-3 activation were also analyzed in the acute phase after HI. RESULTS: MRI
      analysis demonstrated reduced cortical injury in Lf rats few hours post-HI and in
      long-term outcome (P25). Lf reduced HI-induced modifications of the cortical
      metabolism and altered white matter microstructure was recovered in Lf
      supplemented rats at P25. Lf supplementation significantly decreased brain TNF
      alpha and IL-6 gene transcription, increased phosphorylated AKT levels and
      reduced activation of caspase-3 at 24 h post-injury. INTERPRETATION: Lf given
      through lactation to rat pups with cerebral HI injury shows neuroprotective
      effects on brain metabolism, and cerebral gray and white matter recovery. This
      nutritional intervention may be of high interest for the clinical field of
      preterm brain neuroprotection.

PMID- 25574473
TI  - Human brain arteriovenous malformations express lymphatic-associated genes.
AB  - OBJECTIVE: Brain arteriovenous malformations (AVMs) are devastating, hemorrhage
      prone, cerebrovascular lesions characterized by well-defined feeding arteries,
      draining vein(s) and the absence of a capillary bed. The endothelial cells (ECs)
      that comprise AVMs exhibit a loss of arterial and venous specification. Given the
      role of the transcription factor COUP-TFII in vascular development, EC
      specification, and pathological angiogenesis, we examined human AVM tissue to
      determine if COUP-FTII may have a role in AVM disease biology. METHODS: We
      examined 40 human brain AVMs by immunohistochemistry (IHC) and qRT-PCR for the
      expression of COUP-TFII as well as other genes involved in venous and lymphatic
      development, maintenance, and signaling. We also examined proliferation and EC
      tube formation with human umbilical ECs (HUVEC) following COUP-TFII
      overexpression. RESULTS: We report that AVMs expressed COUP-TFII, SOX18, PROX1,
      NFATC1, FOXC2, TBX1, LYVE1, Podoplanin, and vascular endothelial growth factor
      (VEGF)-C, contained Ki67-positive cells and heterogeneously expressed genes
      involved in Hedgehog, Notch, Wnt, and VEGF signaling pathways. Overexpression of
      COUP-TFII alone in vitro resulted in increased EC proliferation and dilated tubes
      in an EC tube formation assay in HUVEC. INTERPRETATION: This suggests AVM ECs are
      further losing their arterial/venous specificity and acquiring a partial
      lymphatic molecular phenotype. There was significant correlation of gene
      expression with presence of clinical edema and acute hemorrhage. While the
      precise role of these genes in the formation, stabilization, growth and risk of
      hemorrhage of AVMs remains unclear, these findings have potentially important
      implications for patient management and treatment choice, and opens new avenues
      for future work on AVM disease mechanisms.

PMID- 25574474
TI  - Inhibiting drug efflux transporters improves efficacy of ALS therapeutics.
AB  - OBJECTIVE: Research identified promising therapeutics in cell models of
      Amyotrophic Lateral Sclerosis (ALS), but there is limited progress translating
      effective treatments to animal models and patients, and ALS remains a disease
      with no effective treatment. One explanation stems from an acquired
      pharmacoresistance driven by the drug efflux transporters P-glycoprotein (P-gp)
      and breast cancer-resistant protein (BCRP), which we have shown are selectively
      upregulated at the blood-brain and spinal cord barrier (BBB/BSCB) in ALS mice and
      patients. Pharmacoresistance is well appreciated in other brain diseases, but
      overlooked in ALS despite many failures in clinical trials. METHODS: Here, we
      prove that a P-gp/BCRP-driven pharmacoresistance limits the bioavailability of
      ALS therapeutics using riluzole, the only FDA-approved drug for ALS and a
      substrate of P-gp and BCRP. ALS mice (SOD1-G93A) were treated with riluzole and
      elacridar, to block P-gp and BCRP, and monitored for survival as well as
      behavioral and physiological parameters. RESULTS: We show that riluzole, which
      normally is not effective when given at onset of symptoms, is now effective in
      the ALS mice when administered in combination with the P-gp/BCRP inhibitor
      elacridar. Chronic elacridar treatment increases riluzole Central nervous system
      (CNS) penetration, improves behavioral measures, including muscle function,
      slowing down disease progression, and significantly extending survival.
      INTERPRETATION: Our approach improves riluzole efficacy with treatment beginning
      at symptom onset. Riluzole will not provide a cure, but enhancing its efficacy
      postsymptoms by addressing pharmacoresistance demonstrates a proof-of-principle
      concept to consider when developing new ALS therapeutic strategies. We highlight
      a novel improved therapeutic approach for ALS and demonstrate that
      pharmacoresistance can no longer be ignored in ALS.

PMID- 25574475
TI  - Mice homozygous for c.451C>T mutation in Cln1 gene recapitulate INCL phenotype.
AB  - OBJECTIVE: Nonsense mutations account for 5-70% of all genetic disorders. In the
      United States, nonsense mutations in the CLN1/PPT1 gene underlie >40% of the
      patients with infantile neuronal ceroid lipofuscinosis (INCL), a devastating
      neurodegenerative lysosomal storage disease. We sought to generate a reliable
      mouse model of INCL carrying the most common Ppt1 nonsense mutation (c.451C>T)
      found in the United States patient population to provide a platform for
      evaluating nonsense suppressors in vivo. METHODS: We knocked-in c.451C>T nonsense
      mutation in the Ppt1 gene in C57 embryonic stem (ES) cells using a targeting
      vector in which LoxP flanked the Neo cassette, which was removed from targeted ES
      cells by electroporating Cre. Two independently targeted ES clones were injected
      into blastocysts to generate syngenic C57 knock-in mice, obviating the necessity
      for extensive backcrossing. RESULTS: Generation of Ppt1-KI mice was confirmed by
      DNA sequencing, which showed the presence of c.451C>T mutation in the Ppt1 gene.
      These mice are viable and fertile, although they developed spasticity (a
      "clasping" phenotype) at a median age of 6 months. Autofluorescent storage
      materials accumulated throughout the brain regions and in visceral organs.
      Electron microscopic analysis of the brain and the spleen showed granular
      osmiophilic deposits. Increased neuronal apoptosis was particularly evident in
      cerebral cortex and abnormal histopathological and electroretinographic (ERG)
      analyses attested striking retinal degeneration. Progressive deterioration of
      motor coordination and behavioral parameters continued until eventual death.
      INTERPRETATION: Our findings show that Ppt1-KI mice reliably recapitulate INCL
      phenotype providing a platform for testing the efficacy of existing and novel
      nonsense suppressors in vivo.

PMID- 25574477
TI  - Pituitary adenylate cyclase activating polypeptide and migraine.
AB  - Pituitary adenylate cyclase activating peptide (PACAP) is found in human
      trigeminocervical complex and can trigger migraine. PACAP levels were measured
      using a sensitive radioimmunoassay. Stimulation of the superior sagittal sinus
      (SSS) in cat elevated PACAP levels in cranial blood. Patients with moderate or
      severe migraine headache had elevated PACAP in the external jugular vein during
      headache (n = 15), that was reduced 1 h after treatment with sumatriptan 6 mg (n
      = 11), and further reduced interictally (n = 9). The data suggest PACAP, or its
      receptors, are a promising target for migraine therapeutics. 

PMID- 25574478
TI  - Brain iron quantification by MRI in mitochondrial membrane protein-associated
      neurodegeneration under iron-chelating therapy.
AB  - Therapeutic trials for Neurodegeneration with Brain Iron Accumulation have aimed
      at a reduction of cerebral iron content. A 13-year-old girl with mitochondrial
      membrane protein-associated neurodegeneration treated with an iron-chelating
      agent was monitored by R2 relaxometry, R2* relaxometry, and quantitative
      susceptibility mapping to estimate the brain iron content. The highly increased
      brain iron content slowly decreased in the substantia nigra but remained stable
      for globus pallidus. The estimated iron content was higher by R2* compared to R2
      and quantitative susceptibility mapping, a finding not previously observed in the
      brain of healthy volunteers. A hypothesis explaining this discrepancy is offered.

PMID- 25574476
TI  - Mutations in PTRH2 cause novel infantile-onset multisystem disease with
      intellectual disability, microcephaly, progressive ataxia, and muscle weakness.
AB  - OBJECTIVE: To identify the cause of a so-far unreported phenotype of infantile
      onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD).
      METHODS: We characterized a consanguineous family of Yazidian-Turkish descent
      with IMNEPD. The two affected children suffer from intellectual disability,
      postnatal microcephaly, growth retardation, progressive ataxia, distal muscle
      weakness, peripheral demyelinating sensorimotor neuropathy, sensorineural
      deafness, exocrine pancreas insufficiency, hypothyroidism, and show signs of
      liver fibrosis. We performed whole-exome sequencing followed by bioinformatic
      analysis and Sanger sequencing on affected and unaffected family members. The
      effect of mutations in the candidate gene was studied in wild-type and mutant
      mice and in patient and control fibroblasts. RESULTS: In a consanguineous family
      with two individuals with IMNEPD, we identified a homozygous frameshift mutation
      in the previously not disease-associated peptidyl-tRNA hydrolase 2 (PTRH2) gene.
      PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated
      cell survival and apoptosis signaling. We show that PTRH2 is highly expressed in
      the developing brain and is a key determinant in maintaining cell survival during
      human tissue development. Moreover, we link PTRH2 to the mTOR pathway and thus
      the control of cell size. The pathology suggested by the human phenotype and
      neuroimaging studies is supported by analysis of mutant mice and patient
      fibroblasts. INTERPRETATION: We report a novel disease phenotype, show that the
      genetic cause is a homozygous mutation in the PTRH2 gene, and demonstrate
      functional effects in mouse and human tissues. Mutations in PTRH2 should be
      considered in patients with undiagnosed multisystem neurologic, endocrine, and
      pancreatic disease.

PMID- 25574479
TI  - Sirtuin 1 activator SRT2104 protects Huntington's disease mice.
AB  - Sirtuin 1 is a nicotinamide adenine dinucleotide-dependent protein deacetylase
      which regulates longevity and improves metabolism. Activation of Sirtuin 1
      confers beneficial effects in models of neurodegenerative diseases. We and others
      have provided convincing evidence that overexpression of Sirtuin 1 plays a
      neuroprotective role in mouse models of Huntington's disease. In this study, we
      report that SRT2104, a small molecule Sirtuin 1 activator, penetrated the blood
      brain barrier, attenuated brain atrophy, improved motor function, and extended
      survival in a mouse model of Huntington's disease. These findings imply a novel
      therapeutic strategy for Huntington's disease by targeting Sirtuin 1. 

PMID- 25574480
TI  - Laing distal myopathy pathologically resembling inclusion body myositis.
AB  - Mutations in MYH7 cause autosomal dominant Laing distal myopathy. We present a
      family with a previously reported deletion (c.5186_5188delAGA, p.K1729del).
      Muscle pathology in one family member was characterized by an inflammatory
      myopathy with rimmed vacuoles, increased MHC Class I expression, and perivascular
      and endomysial muscle inflammation comprising CD3(+), CD4(+), CD8(+), and CD68(+)
      inflammatory cells. Interestingly, this biopsy specimen contained TDP-43, p62,
      and SMI-31-positive protein aggregates typical of inclusion body myositis. These
      findings should alert physicians to the possibility that patients with MYH7
      mutations may have muscle biopsies showing pathologic findings similar to
      inclusion body myositis. 

PMID- 25574483
TI  - Meat production in a feedlot system of Zebu-Holstein steers and heifers with
      dairy genetics: productive and biological analyses.
AB  - The aim of this study was to evaluate the productive and biological efficiency of
      steers and heifers from dairy genetics in a feedlot system in terms of meat
      production. Twenty-four steers and 24 heifers at 10 monthes of age, (3/4) Zebu *
      (1/4) Holstein were utilized. They were distributed over four feedlot times, 30,
      60, 90, and 120 days with four replications for each sex, and were slaughtered at
      the end of each period. The productive and biological analyses were performed
      through comparative slaughter to determine the body composition. Heifers
      presented with greater intakes (P < 0.05) of dry matter in grams per kg of body
      weight. Steers presented with a greater (P < 0.05) final empty body weight,
      carcass gain, cold carcass weight, and meat proportion in the carcass; however,
      heifers presented with a greater subcutaneous fat thickness (P < 0.05) and,
      consequently, a greater (P < 0.05) fat proportion in the carcass. We conclude
      that steers are more efficient in their productive performance than heifers in a
      feedlot. For the finishing carcass fat cover, heifers need 90 days in the
      feedlot. The net energy requirements for maintenance are 67 kcal/EBW(0.75)/d, and
      the net requirements of energy (NEg) and protein (NPg) for gain can be estimated
      by the following equations: NEg(Mcal/d) = 0.067 * EBW(0.75) * EBG(1.095) and NPg
      = 162 * EBG - 5.62 * RE for the two sexes. 

PMID- 25574482
TI  - Kappa Opioid Receptor Agonist and Brain Ischemia.
AB  - Opioid receptors, especially Kappa opioid receptor (KOR) play an important role
      in the pathophysiological process of cerebral ischemia reperfusion injury.
      Previously accepted KOR agonists activity has included anti-nociception,
      cardiovascular, anti-pruritic, diuretic, and antitussive effects, while
      compelling evidence from various ischemic animal models indicate that KOR agonist
      have neuroprotective effects through various mechanisms. In this review, we aimed
      to demonstrate the property of KOR agonist and its role in global and focal
      cerebral ischemia. Based on current preclinical research, the KOR agonists may be
      useful as a neuroprotective agent. The recent discovery of salvinorin A, highly
      selective non-opioid KOR agonist, offers a new tool to study the role of KOR in
      brain HI injury and the protective effects of KOR agonist. The unique
      pharmacological profile of salvinorin A along with the long history of human
      usage provides its high candidacy as a potential alternative medication for brain
      HI injury.

PMID- 25574484
TI  - Water quality of urban streams: the Allium cepa seeds/seedlings test as a tool
      for surface water monitoring.
AB  - The present study investigates the genotoxic, mutagenic, and cytotoxic potential
      of surface waters in urban streams using Allium cepa and analyzes the
      applicability of this assay for environmental monitoring. Water samples were
      collected from three streams located in the urban area of a municipality in the
      south of Brazil. For each stream, two samples were collected, one upstream and
      one downstream of the pollution discharge site. Physicochemical evaluation
      indicated that all samples had various degrees of environmental impact, but
      substantial impact was seen for the downstream samples of the Preto and Pedras
      streams. All samples increased the frequency of chromosome aberrations (P <
      0.05). The sample from Pedras downstream site also caused a decrease in mitotic
      index (P < 0.08) and increase in micronuclei (P < 0.08) frequency, indicating
      potential cytotoxicity and mutagenicity. The Pedras stream receives mixed
      industrial and urban wastewater, while the Lajeado and Preto streams receive
      wastewater predominantly domestic in nature, which may partially explain the
      difference in toxicity among the samples. Moreover, the Allium cepa
      seeds/seedlings were shown to be extremely sensitive in detecting the
      genotoxicity of environmental water samples and can be applied as the first tool
      for environmental health hazard identification and prediction. 

PMID- 25574485
TI  - Effect of gamma irradiation on structural and biological properties of a PLGA-PEG
      hydroxyapatite composite.
AB  - Gamma irradiation is able to affect various structural and biological properties
      of biomaterials In this study, a composite of Hap/PLGA-PEG and their ingredients
      were submitted to gamma irradiation doses of 25 and 50 KGy. Various properties
      such as molecular weight (GPC), thermal behavior (DSC), wettability (contact
      angle), cell viability (MTT assay), and alkaline phosphatase activity were
      studied for the composites and each of their ingredients. The results showed a
      decrease in molecular weight of copolymer with no change in the glass transition
      and melting temperatures after gamma irradiation. In general gamma irradiation
      can increase the activation energy DeltaH of the composites and their
      ingredients. While gamma irradiation had no effect on the wettability of
      copolymer samples, there was a significant decrease in contact angle of
      hydroxyapatite and composites with increase in gamma irradiation dose. This study
      showed an increase in biocompatibility of hydroxyapatite with gamma irradiation
      with no significant effect on cell viability in copolymer and composite samples.
      In spite of the fact that no change occurred in alkaline phosphatase activity of
      composite samples, results indicated a decrease in alkaline phosphatase activity
      in irradiated hydroxyapatites. These effects on the properties of PLGA-PEG
      hydroxyapatite can enhance the composite application as a biomaterial. 

PMID- 25574486
TI  - Experimental evaluation of sodium silicate-based nanosilica against chloride
      effects in offshore concrete.
AB  - This study investigates the effect of a new pore filling material, named sodium
      silicate-based nanosilica (SS), on resisting the diffusion of the chloride ions.
      The proposed SS is chosen, mainly due to its smaller particle size, compared to
      the conventional ethyl silicate-based nanosilica. Each particle of SS is
      chemically treated to have the negative (-) charge on its surface. Four types of
      mixes with different amounts of partial replacement with fly ash and slag are
      prepared. Effect of water to binder ratios (0.35, 0.40, and 0.45) is also
      examined. Test results showed that the inclusion of SS was significantly
      beneficial for protecting the concrete from chloride attack. At a given strength,
      the SS inclusion in concrete was up to three times more effective than the
      control concrete without SS. It is believed that these excellent results are
      attributed to the small particle size and the chemical surface treatment of SS.
      In this study, experiments of compressive strength, hydration heat, accelerated
      neutralization, and sulfate erosion tests were also conducted to find the general
      effect of SS inclusion on the fundamental properties and durability of concrete. 

PMID- 25574487
TI  - Aspect of thrombolytic therapy: a review.
AB  - Thrombolytic therapy, also known as clot busting drug, is a breakthrough
      treatment which has saved untold lives. It has been used in the clinical area to
      treat venous and arterial thromboembolic complaints which are a foremost cause of
      death. In 1761, Morgagni lead the way of thrombolytic therapy. Now day's
      different types of thrombolytic drugs are currently available in market:
      alteplase, anistreplase, urokinase, streptokinase, tenecteplase, and so forth.
      Thrombolytic therapy should be given with maintaining proper care in order to
      minimize the risk of clinically important bleeding as well as enhance the chances
      of successfully thrombolysis of clot. These cares include preinfusion care,
      during the infusion care, and postinfusion care. Besides proper knowledge of
      contraindication, evolutionary factor, and combination of drug is essential for
      successful thrombolytic therapy. In these review we discussed about these aspect
      of thrombolytic therapy. 

PMID- 25574488
TI  - White mulberry (Morus alba) foliage methanolic extract can alleviate Aeromonas
      hydrophila infection in African catfish (Clarias gariepinus).
AB  - Two experiments were simultaneously conducted with Morus alba (white mulberry)
      foliage extract (MFE) as a growth promoter and treatment of Aeromonas hydrophila
      infection in separate 60 and 30 days trail (Experiments 1 and 2, resp.) in
      African catfish (Clarias gariepinus). In Experiment 1, four diets, control and
      control supplemented with 2, 5, or 7 g MFE/kg dry matter (DM) of diet, were used.
      In Experiment 2, fish were intraperitoneally infected with Aeromonas hydrophila
      and fed the same diets as experiment 1 plus additional two diets with or without
      antibiotic. Results of experiment 1 showed that growth was unaffected by dietary
      levels of MFE. Treatments with the inclusion of MFE at the levels of 5 and 7 g/Kg
      DM had no mortality. Red blood cells (RBC), albumin, and total protein were all
      higher for the treatments fed MFE (5 and 7 g/Kg DM). Results of experiment 2
      showed RBC, hemoglobin, hematocrit, globulin, albumin, and total protein improved
      with the increase in MFE in the infected fish. The dietary MFE at the level of 7
      g/kg DM reduced mortality rate. In conclusion, MFE at the level of 7 g/kg DM
      could be a valuable dietary supplement to cure the infected fish. 

PMID- 25574490
TI  - An adaptive handover prediction scheme for seamless mobility based wireless
      networks.
AB  - We propose an adaptive handover prediction (AHP) scheme for seamless mobility
      based wireless networks. That is, the AHP scheme incorporates fuzzy logic with AP
      prediction process in order to lend cognitive capability to handover decision
      making. Selection metrics, including received signal strength, mobile node
      relative direction towards the access points in the vicinity, and access point
      load, are collected and considered inputs of the fuzzy decision making system in
      order to select the best preferable AP around WLANs. The obtained handover
      decision which is based on the calculated quality cost using fuzzy inference
      system is also based on adaptable coefficients instead of fixed coefficients. In
      other words, the mean and the standard deviation of the normalized network
      prediction metrics of fuzzy inference system, which are collected from available
      WLANs are obtained adaptively. Accordingly, they are applied as statistical
      information to adjust or adapt the coefficients of membership functions. In
      addition, we propose an adjustable weight vector concept for input metrics in
      order to cope with the continuous, unpredictable variation in their membership
      degrees. Furthermore, handover decisions are performed in each MN independently
      after knowing RSS, direction toward APs, and AP load. Finally, performance
      evaluation of the proposed scheme shows its superiority compared with
      representatives of the prediction approaches. 

PMID- 25574489
TI  - Effects of polysaccharide elicitors on secondary metabolite production and
      antioxidant response in Hypericum perforatum L. shoot cultures.
AB  - The effects of polysaccharide elicitors such as chitin, pectin, and dextran on
      the production of phenylpropanoids (phenolics and flavonoids) and
      naphtodianthrones (hypericin and pseudohypericin) in Hypericum perforatum shoot
      cultures were studied. Nonenzymatic antioxidant properties (NEAOP) and peroxidase
      (POD) activity were also observed in shoot extracts. The activities of
      phenylalanine ammonia lyase (PAL) and chalcone-flavanone isomerase (CHFI) were
      monitored to estimate channeling in phenylpropanoid/flavonoid pathways of
      elicited shoot cultures. A significant suppression of the production of total
      phenolics and flavonoids was observed in elicited shoots from day 14 to day 21 of
      postelicitation. This inhibition of phenylpropanoid production was probably due
      to the decrease in CHFI activity in elicited shoots. Pectin and dextran promoted
      accumulation of naphtodianthrones, particularly pseudohypericin, within 21 days
      of postelicitation. The enhanced accumulation of naphtodianthrones was positively
      correlated with an increase of PAL activity in elicited shoots. All tested
      elicitors induced NEAOP at day 7, while chitin and pectin showed increase in POD
      activity within the entire period of postelicitation. The POD activity was in
      significantly positive correlation with flavonoid and hypericin contents,
      suggesting a strong perturbation of the cell redox system and activation of
      defense responses in polysaccharide-elicited H. perforatum shoot cultures. 

PMID- 25574491
TI  - Deflection of resilient materials for reduction of floor impact sound.
AB  - Recently, many residents living in apartment buildings in Korea have been
      bothered by noise coming from the houses above. In order to reduce noise
      pollution, communities are increasingly imposing bylaws, including the limitation
      of floor impact sound, minimum thickness of floors, and floor soundproofing
      solutions. This research effort focused specifically on the deflection of
      resilient materials in the floor sound insulation systems of apartment houses.
      The experimental program involved conducting twenty-seven material tests and ten
      sound insulation floating concrete floor specimens. Two main parameters were
      considered in the experimental investigation: the seven types of resilient
      materials and the location of the loading point. The structural behavior of sound
      insulation floor floating was predicted using the Winkler method. The
      experimental and analytical results indicated that the cracking strength of the
      floating concrete floor significantly increased with increasing the tangent
      modulus of resilient material. The deflection of the floating concrete floor
      loaded at the side of the specimen was much greater than that of the floating
      concrete floor loaded at the center of the specimen. The Winkler model
      considering the effect of modulus of resilient materials was able to accurately
      predict the cracking strength of the floating concrete floor. 

PMID- 25574492
TI  - Head and maxillofacial injuries in child and adolescent victims of automotive
      accidents.
AB  - BACKGROUND: Victims of motor vehicle accidents may suffer multiple lesions,
      including maxillofacial injuries. The aim of this study was to evaluate the
      prevalence and factors associated with head, facial, and maxillofacial injuries
      in child and adolescent victims of automobile accidents. A cross-sectional study
      was carried out with analysis of forensic medical reports from the Legal Medical
      Institute of Campina Grande, Brazil, between January 2008 and December 2011.
      Descriptive and inferential statistical analysis was conducted using the chi
      square test (alpha = 0.05). From 1613 medical reports analyzed, the sample is
      composed 232 (14.4%) reports referring to child and adolescent victims of
      automobile accidents aged 0-19 years of both sexes. Victims were mostly
      adolescents aged from 15 to 19 years (64.2%), males (73.7%), and motorcyclists
      (51.3%). More than half of the victims had single lesions (54.3%) located in the
      head (20.7%) and face (21.6%). Head injuries occurred more frequently in children
      aged 0-4 years (53.8%, PR = 5.065, 95% CI = 1.617-5.870) and pedestrians (30.4%,
      PR = 2.039, 95% CI = 1.024-4.061), while facial and maxillofacial injuries
      occurred in higher proportion among females (31.1%, PR = 0.489, 95% CI = 0.251
      0.954). Our findings suggest that accidents involving motorcyclists are the most
      prevalent, affecting male adolescents aged from 15 to 19 years, resulting in a
      high frequency of injuries in the head and face regions.

PMID- 25574493
TI  - A preliminary appraisal of the effect of pumping on seawater intrusion and
      upconing in a small tropical island using 2D resistivity technique.
AB  - The existing knowledge regarding seawater intrusion and particularly upconing, in
      which both problems are linked to pumping, entirely relies on theoretical
      assumptions. Therefore, in this paper, an attempt is made to capture the effects
      of pumping on seawater intrusion and upconing using 2D resistivity measurement.
      For this work, two positions, one perpendicular and the other parallel to the
      sea, were chosen as profile line for resistivity measurement in the coastal area
      near the pumping wells of Kapas Island, Malaysia. Subsequently, water was pumped
      out of two pumping wells simultaneously for about five straight hours. Then,
      immediately after the pumping stopped, resistivity measurements were taken along
      the two stationed profile lines. This was followed by additional measurements
      after four and eight hours. The results showed an upconing with low resistivity
      of about 1-10 Omegam just beneath the pumping well along the first profile line
      that was taken just after the pumping stopped. The resistivity image also shows
      an intrusion of saline water (water enriched with diluted salt) from the sea
      coming towards the pumping well with resistivity values ranging between 10 and 25
      Omegam. The subsequent measurements show the recovery of freshwater in the
      aquifer and how the saline water is gradually diluted or pushed out of the
      aquifer. Similarly the line parallel to the sea (L2) reveals almost the same
      result as the first line. However, in the second and third measurements, there
      were some significant variations which were contrary to the expectation that the
      freshwater may completely flush out the saline water from the aquifer. These two
      time series lines show that as the areas with the lowest resistivity (1 Omegam)
      shrink with time, the low resistivity (10 Omegam) tends to take over almost the
      entire area implying that the freshwater-saltwater equilibrium zone has already
      been altered. These results have clearly enhanced our current understanding and
      add more scientific weight to the theoretical assumptions on the effects of
      pumping on seawater intrusion and upconing. 

PMID- 25574494
TI  - The structure of EAP-groups and self-autopermutable subgroups.
AB  - A subgroup H of a given group G is said to be autopermutable, if HH(alpha) =
      H(alpha)H for all alpha ? Aut(G). We also call H a self-autopermutable subgroup
      of G, when HH(alpha) = H(alpha)H implies that H(alpha) = H. Moreover, G is said
      to be EAP-group, if every subgroup of G is autopermutable. One notes that if
      alpha runs over the inner automorphisms of the group, one obtains the notions of
      conjugate-permutability, self-conjugate-permutability, and ECP-groups, which were
      studied by Foguel in 1997, Li and Meng in 2007, and Xu and Zhang in 2005,
      respectively. In the present paper, we determine the structure of a finite EAP
      group when its centre is of index 4 in G. We also show that self
      autopermutability and characteristic properties are equivalent for nilpotent
      groups.

PMID- 25574496
TI  - Design, synthesis, molecular docking, and antibacterial evaluation of some novel
      flouroquinolone derivatives as potent antibacterial agent.
AB  - OBJECTIVE: Quinolone moiety is an important class of nitrogen containing
      heterocycles widely used as key building blocks for medicinal agents. It exhibits
      a wide spectrum of pharmacophores and has bactericidal, antiviral, antimalarial,
      and anticancer activities. In view of the reported antimicrobial activity of
      various fluoroquinolones, the importance of the C-7 substituents is that they
      exhibit potent antimicrobial activities. Our objective was to synthesize newer
      quinolone analogues with increasing bulk at C-7 position of the main 6
      fluoroquinolone scaffold to produce the target compounds which have potent
      antimicrobial activity. METHODS: A novel series of 1-ethyl-6-fluoro-4-oxo-7-{4-[2
      (4-substituted phenyl)-2-(substituted)-ethyl]-1-piperazinyl}-1,4-dihydroquinoline
      3-carboxylic acid derivatives were synthesized. To understand the interaction of
      binding sites with bacterial protein receptor, the docking study was performed
      using topoisomerase II DNA gyrase enzymes (PDB ID: 2XCT) by Schrodinger's Maestro
      program. In vitro antibacterial activity of the synthesized compounds was studied
      and the MIC value was calculated by the broth dilution method. RESULTS: Among all
      the synthesized compounds, some compounds showed potent antimicrobial activity.
      The compound 8g exhibited good antibacterial activity. CONCLUSION: This
      investigation identified the potent antibacterial agents against certain
      infections.

PMID- 25574495
TI  - Effects of glucomannan-enriched, aronia juice-based supplement on cellular
      antioxidant enzymes and membrane lipid status in subjects with abdominal obesity.
AB  - The aim of this study was to analyze the effects of a 4-week-long consumption of
      glucomannan-enriched, aronia juice-based supplement on anthropometric parameters,
      membrane fatty acid profile, and status of antioxidant enzymes in erythrocytes
      obtained from postmenopausal women with abdominal obesity. Twenty women aged 45
      65 with a mean body mass index (BMI) of 36.1 +/- 4.4 kg/m(2) and waist
      circumference of 104.8 +/- 10.1 cm were enrolled. Participants were instructed to
      consume 100 mL of supplement per day as part of their regular diet. A significant
      increase in the content of n-3 (P < 0.05) polyunsaturated fatty acids in membrane
      phospholipids was observed, with a marked increase in the level of
      docosahexaenoic fatty acid (P < 0.05). Accordingly, a decrease in the n-6 and n-3
      fatty acids ratio was observed (P < 0.05). The observed effects were accompanied
      with an increase in glutathione peroxidase activity (P < 0.05). Values for BMI (P
      < 0.001), waist circumference (P < 0.001), and systolic blood pressure (P < 0.05)
      were significantly lower after the intervention. The obtained results indicate a
      positive impact of tested supplement on cellular oxidative damage, blood
      pressure, and anthropometric indices of obesity. 

PMID- 25574497
TI  - Full-length sequence analysis of chloroquine resistance transporter gene in
      Plasmodium falciparum isolates from Sabah, Malaysia.
AB  - Chloroquine resistance (CQR) in falciparum malaria was identified to be
      associated with several mutations in the chloroquine resistance transporter gene
      (pfcrt) that encodes the transmembrane transporter in digestive vacuole membrane
      of the parasite. This study aimed to investigate the point mutations across the
      full-length pfcrt in Plasmodium falciparum isolates in Sabah, Malaysia. A total
      of 31 P. falciparum positive samples collected from Keningau, Kota Kinabalu, and
      Kudat, Sabah, were analyzed. pfcrt was PCR amplified and cloned prior to sequence
      analysis. This study showed that all the previously described 10 point mutations
      associated with CQR at codons 72, 74, 75, 76, 97, 220, 271, 326, 356, and 371
      were found with different prevalence. Besides, two novel point mutations, I166V
      and H273N, were identified with 22.5% and 19.3%, respectively. Three haplotypes,
      namely, CVMNK (29%), CVIET (3.2%), and SVMNT (67.7%), were identified. High
      prevalence of SVMNT among P. falciparum isolates from Sabah showed that these
      isolates are closer to the P. falciparum isolates from Papua New Guinea rather
      than to the more proximal Southeast Asian CVIET haplotype. Full-length analysis
      of pfcrt showed that chloroquine resistant P. falciparum in Sabah is still
      prevalent despite the withdrawal of chloroquine usage since 1979. 

PMID- 25574498
TI  - Double barreled wet colostomy: initial experience and literature review.
AB  - BACKGROUND: Pelvic exenteration and multivisceral resection in colorectal have
      been described as a curative and palliative intervention. Urinary tract
      reconstruction in a pelvic exenteration is achieved in most cases with an ileal
      conduit of Bricker, although different urinary reservoirs have been described.
      METHODS: A retrospective and observational study of six patients who underwent a
      pelvic exenteration and urinary tract reconstruction with a double barreled wet
      colostomy (DBWC) was done, describing the preoperative diagnosis, the indication
      for the pelvic exenteration, the complications associated with the procedure, and
      the followup in a period of 5 years. A literature review of the case series
      reported of the technique was performed. RESULTS: Six patients had a urinary
      tract reconstruction with the DBWC technique, 5 male patients and one female
      patient. Age range was from 20 to 77 years, with a medium age 53.6 years. The
      most frequent complication presented was a pelvic abscess in 3 patients (42.85%);
      all complications could be resolved with a conservative treatment. CONCLUSION: In
      the group of our patients with pelvic exenteration and urinary tract
      reconstruction with a DBWC, it is a safe procedure and well tolerated by the
      patients, and most of the complications can be resolved with conservative
      treatment.

PMID- 25574499
TI  - MMPI-2: cluster analysis of personality profiles in perinatal depression
      preliminary evidence.
AB  - BACKGROUND: To assess personality characteristics of women who develop perinatal
      depression. METHODS: The study started with a screening of a sample of 453 women
      in their third trimester of pregnancy, to which was administered a survey data
      form, the Edinburgh Postnatal Depression Scale (EPDS) and the Minnesota
      Multiphasic Personality Inventory 2 (MMPI-2). A clinical group of subjects with
      perinatal depression (PND, 55 subjects) was selected; clinical and validity
      scales of MMPI-2 were used as predictors in hierarchical cluster analysis carried
      out. RESULTS: The analysis identified three clusters of personality profile: two
      "clinical" clusters (1 and 3) and an "apparently common" one (cluster 2). The
      first cluster (39.5%) collects structures of personality with prevalent obsessive
      or dependent functioning tending to develop a "psychasthenic" depression; the
      third cluster (13.95%) includes women with prevalent borderline functioning
      tending to develop "dysphoric" depression; the second cluster (46.5%) shows a
      normal profile with a "defensive" attitude, probably due to the presence of
      defense mechanisms or to the fear of stigma. CONCLUSION: Characteristics of
      personality have a key role in clinical manifestations of perinatal depression;
      it is important to detect them to identify mothers at risk and to plan targeted
      therapeutic interventions.

PMID- 25574500
TI  - Appendicitis in children: evaluation of the pediatric appendicitis score in
      younger and older children.
AB  - Background. This study aimed to evaluate Pediatric Appendicitis Score (PAS),
      diagnostic delay, and factors responsible for possible late diagnosis in children
      <4 years compared with older children who were operated on for suspected
      appendicitis. Method. 122 children, between 1 and 14 years, operated on with
      appendectomy for suspected appendicitis, were retrospectively analyzed. The
      cohort was divided into two age groups: >=4 years (n = 102) and <4 years (n =
      20). Results. The mean PAS was lower among the younger compared with the older
      patients (5.3 and 6.6, resp.; P = 0.005), despite the fact that younger children
      had more severe appendicitis (75.0% and 33.3%, resp.; P = 0.001). PAS had low
      sensitivity in both groups, with a significantly lower sensitivity among the
      younger patients. Parent and doctor delay were confirmed in children <4 years of
      age with appendicitis. PAS did not aid in patients with doctor delay. Parameters
      in patient history, symptoms, and abdominal examination were more diffuse in
      younger children. Conclusion. PAS should be used with caution when examining
      children younger than 4 years of age. Diffuse symptoms in younger children with
      acute appendicitis lead to delay and to later diagnosis and more complicated
      appendicitis. 

PMID- 25574502
TI  - Recovery Support for Adolescents with Substance use Disorders: The Impact of
      Recovery Support Telephone Calls Provided by Pre-Professional Volunteers.
AB  - The present quasi-experiment examined the direct and indirect effects of recovery
      support telephone calls following adolescent substance use disorder treatment.
      Six-month outcome data from 202 adolescents who had received recovery support
      calls from primarily pre-professional (i.e., college-level social service
      students) volunteers was compared to 6-month outcome data from a matched
      comparison sample of adolescents (n = 404). Results suggested adolescents in the
      recovery support sample had significantly greater reductions in their recovery
      environment risk relative to the comparison sample (beta = -.17). Path analysis
      also suggested that the reduction in recovery environment risk produced by
      recovery support calls had indirect impacts (via recovery environment risk) on
      reductions in social risk (beta = .22), substance use (beta = .23), and substance
      related problems (beta = .16). Finally, moderation analyses suggested the effects
      of recovery support calls did not differ by gender, but were significantly
      greater for adolescents with lower levels of treatment readiness. In addition to
      providing rare empirical support for the effectiveness of recovery support
      services, an important contribution of this study is that it provides evidence
      that recovery support services do not necessarily have to be "peer-based," at
      least in terms of the recovery support service provider having the experiential
      credentials of being "in recovery." If replicated, this latter finding may have
      particularly important implications for helping increase the recovery support
      workforce.

PMID- 25574503
TI  - Challenges to Recruitment of Urban African American Patients with Cancer Pain.
AB  - There are many assumptions about recruitment of African Americans to cancer
      studies. The population is often characterized as older, low income, with limited
      education, scarce resources, and distrust of the health care system. Support
      systems for African Americans are reported to be centered on family and church
      communities. Observations made during recruitment and enrollments for a
      longitudinal intervention study with urban African Americans with cancer pain are
      presented. Majority of the subjects being recruited in this study are well
      educated, knowledgeable about research and very open to healthcare providers and
      researchers. Our population is younger than anticipated and struggling with an
      absence of family, faith, or community supports. They are more connected in terms
      of phone ownership, but often difficult to contact due to interruptions in phone
      service, housing insecurity and time demands related to medical care for their
      cancer. We conclude that familiarity with cultural patterns of a population of
      interest is necessary, but local and individual assessment is critical to
      successful recruitment to research.

PMID- 25574501
TI  - Mechanisms of Myofascial Pain.
AB  - Myofascial pain syndrome is an important health problem. It affects a majority of
      the general population, impairs mobility, causes pain, and reduces the overall
      sense of well-being. Underlying this syndrome is the existence of painful taut
      bands of muscle that contain discrete, hypersensitive foci called myofascial
      trigger points. In spite of the significant impact on public health, a clear
      mechanistic understanding of the disorder does not exist. This is likely due to
      the complex nature of the disorder which involves the integration of cellular
      signaling, excitation-contraction coupling, neuromuscular inputs, local
      circulation, and energy metabolism. The difficulties are further exacerbated by
      the lack of an animal model for myofascial pain to test mechanistic hypothesis.
      In this review, current theories for myofascial pain are presented and their
      relative strengths and weaknesses are discussed. Based on new findings linking
      mechanoactivation of reactive oxygen species signaling to destabilized calcium
      signaling, we put forth a novel mechanistic hypothesis for the initiation and
      maintenance of myofascial trigger points. It is hoped that this lays a new
      foundation for understanding myofascial pain syndrome and how current therapies
      work, and gives key insights that will lead to the improvement of therapies for
      its treatment.

PMID- 25574504
TI  - Conceptualizing Social Recovery: Recovery Routes of Methamphetamine Users.
AB  - The goal of our qualitative study was to gain a phenomenological understanding of
      routes to recovery from problematic drug use. In-depth interviews and drug
      histories were collected from 50 former methamphetamine users recruited from a
      U.S. metropolitan suburb who identified as having had problematic use of this
      drug in the past. Transcripts of the audio-recorded interviews were coded for
      common themes regarding types of recovery strategies or tools employed on the
      route to recovery. The common strategies used for recovery from problematic
      methamphetamine use in all routes were social in nature and did not necessarily
      include cessation of all substances. Based on our findings, we suggest a
      conceptualization of social recovery that focuses on reducing the social harms
      caused by problematic drug use rather than focusing primarily on cessation of all
      drug use. Social recovery may be employed as both a treatment strategy and
      analytical tool. More research is needed to advance the concept of social
      recovery for intervention, drug policy, and criminal justice implications.

PMID- 25574505
TI  - HIV: 3 cases that hid in plain sight.
AB  - Having a high index of suspicion is key to recognizing the signs of HIV infection
      in patients without classic risk factors. How quickly would you have spotted
      these 3 cases? 

PMID- 25574506
TI  - PURLs: helmets for positional skull deformities: a good idea, or not?
AB  - Probably not. Helmets appear to be no more effective than waiting for natural
      skull growth to correct the shape of an infant's head. 

PMID- 25574507
TI  - Annular plaques on the back and flanks.
AB  - An 86-year-old African American woman sought care for an asymptomatic rash on her
      back and flanks that she'd had for 14 months. Physical examination of her trunk
      revealed 3 to 6 cm annular/arcuate plaques with central clearing. The lesions
      also had a delicate trailing scale behind a slightly raised erythematous rim. The
      combination of a ring-shaped rash on the patient's torso and a foot infection led
      us to the diagnosis. 

PMID- 25574508
TI  - Addressing Alzheimer's: a pragmatic approach.
AB  - Family physicians are ideally positioned to support patients with Alzheimer's and
      their families through all facets of the disease, from initial diagnosis to end
      of-life care. 

PMID- 25574509
TI  - Tuberculosis: which drug regimen and when.
AB  - Early treatment can prevent mortality, but there are differences in treating
      latent vs active TB. This resource--with drug reference charts--can guide your
      care. 

PMID- 25574510
TI  - Hyperthyroidism . myalgia . rapidly progressing paralysis . Dx?
AB  - A 26-year-old Hispanic woman presented to the emergency department (ED) with
      myalgia and weakness. There were no prior symptoms and family history was
      negative for endocrinopathies. She was admitted and started on methimazole 10 mg
      twice a day for thyroid suppression and given propranolol 10 mg twice a day for
      anticipated hyperadrenergic adverse effects. The remainder of her hospital stay
      was uneventful and she was discharged 6 days after admission. Soon after, an
      outpatient thyroid scan ordered by her primary care physician confirmed that the
      patient had Graves' disease. 

PMID- 25574511
TI  - Clinical inquiry: do annual pelvic exams benefit asymptomatic women who receive
      regular Pap smears?
AB  - No evidence exists to support a clinical benefit from annual pelvic examinations
      for asymptomatic women who receive Pap smears every 3 to 5 years. However, the
      American College of Obstetricians and Gynecologists (ACOG) committee on
      gynecologic practice recommends annual pelvic exams. 

PMID- 25574512
TI  - A disease that strikes close to home.

PMID- 25574513
TI  - Easy bruising . low platelet count . recent cold-like illness . Dx?
AB  - A 6-year-old girl was brought to the emergency department (ED) by her mother
      after the child had bumped her head while playing. While the physician examined
      the child's head, the mother remarked that her daughter had recently developed
      bruises that appeared suddenly and only after minor, if any, known trauma. 

PMID- 25574514
TI  - Antinuclear antibodies: when to test and how to interpret findings.
AB  - Order ANA assays only when clinical features suggest a connective tissue
      disorder. Let ANA immunofluorescent patterns direct additional testing decisions.

PMID- 25574515
TI  - Well-defined macules on young girl's forearms.
AB  - Speaking to the teen without her mother in the room made the diagnosis crystal
      clear. 

PMID- 25574519
TI  - Infrared imaging of primary melanomas reveals hints of regional and distant
      metastases.
AB  - Melanoma is the deadliest form of skin cancer. Metastatic melanomas are resistant
      to almost all existing adjuvant therapies such as chemotherapy and radiotherapy,
      so detection of metastases remains a challenge, and no biomarkers are currently
      available to detect primary tumors with the highest risk of metastasis. Results
      presented in this paper show that Fourier Transform Infrared (FTIR) imaging of
      histological sections followed by supervised partial least squares discriminant
      analysis (PLS-DA) can accurately (>90%) identify the main cell types commonly
      found in melanoma tumors. Here we define six cell types: melanoma cells,
      erythrocytes, connective tissue (includes blood vessel walls, dermis and collagen
      regions), keratinocytes, lymphocytes and necrotic cells. Interestingly, more than
      98% of the melanoma cells are correctly identified. The spectra of the cells
      identified as melanomas were then further analyzed. First, we compared melanoma
      cells in primary tumors (from 26 patients) with melanoma cells from metastases
      (from 25 patients). Neither supervised nor unsupervised analyses revealed any
      significant difference. Similarly, we found no significant correlation between
      the infrared spectra of melanoma cells and the number of proliferative cells
      assessed by Ki67 immunostaining. Finally, we compared the infrared spectra of
      primary tumors from patients diagnosed at different stages of the disease.
      Infrared spectroscopy was capable of pointing out differences between primary
      tumors of patients at stage I or II and patients at stage III or IV, even by
      unsupervised analysis. We then developed a supervised PLS-DA model capable of
      predicting whether tumor cells belonged to one of the two aggregated disease
      stage groups. The model predicted a high rate of true positives (sensitivity of
      88.9%) and a good rate of true negatives (specificity of 70.6%) in external
      validation. These results demonstrate that infrared spectroscopy can be used to
      help identify melanoma characteristics related to the cells' invasive capability.

PMID- 25574520
TI  - Design of molecularly imprinted conducting polymer protein-sensing films via
      substrate-dopant binding.
AB  - Addressing the challenge of protein biosensing using molecularly imprinted
      polymers (MIP), we have developed and tested a novel approach to creating sensing
      conducive polymer films imprinted with a protein substrate, ricin toxin chain A
      (RTA). Our approach for creating MIP protein sensing films is based on a concept
      of substrate-guided dopant immobilization with subsequent conducting polymer film
      formation. In this proof-of-concept work we have tested three macromolecular
      dopants with strong protein affinity, Ponceau S, Coomassie BB R250 and iota
      Carrageenan. The films were formed using sequential interactions of the
      substrate, dopant and pyrrole, followed by electrochemical polymerization. The
      films were formed on gold array electrodes allowing for extensive data
      acquisition. The thickness of the films was optimized to allow for efficient
      substrate extraction, which was removed by a combination of protease and
      detergent treatment. The MIP films were tested for substrate rebinding using
      electrochemical impedance spectroscopy (EIS). The presence of macromolecular
      dopants was essential for MIP film specificity. Out of three dopants tested, RTA
      imprinted polypyrrole films doped with Coomassie BB performed with highest
      specificity towards detection of RTA with a level of detection (LOD) of 0.1 ng
      ml(-1). 

PMID- 25574521
TI  - The pituitary gland under infrared light - in search of a representative spectrum
      for homogeneous regions.
AB  - The pituitary gland is a small but vital organ in the human body. It is located
      at the base of the brain and is often described as the master gland due to its
      multiple functions. The pituitary gland secretes and stores hormones, such as the
      thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), growth
      hormone (hGH), prolactin, gonadotropins, and luteinizing hormones, as well as the
      antidiuretic hormone (ADH). A proper diagnosis of pituitary disorders is of
      utmost importance as this organ participates in regulating a variety of body
      functions. Typical histopathological analysis provides much valuable information,
      but it gives no insight into the biochemical background of the changes that occur
      within the gland. One approach that could be used to evaluate the biochemistry of
      tissue sections obtained from pituitary disorders is Fourier Transform Infra-Red
      (FTIR) spectromicroscopy. In order to collect diagnostically valuable information
      large areas of tissue must be investigated. This work focuses on obtaining a
      unique and representative FTIR spectrum characteristic of one type of cell
      architecture within a sample. The idea presented is based on using hierarchical
      cluster analysis (HCA) for data evaluation to search for uniform patterns within
      samples from the perspective of FTIR spectra. The results obtained demonstrate
      that FTIR spectromicroscopy, combined with proper statistical evaluation, can be
      treated as a complementary method for histopathological analysis and ipso facto
      can increase the sensitivity and specificity for detecting various disorders not
      only for the pituitary gland, but also for other human tissues. 

PMID- 25574522
TI  - Fabrication of novel chemosensors composed of rhodamine derivative for the
      detection of ferric ion and mechanism studies on the interaction between sensor
      and ferric ion.
AB  - Although many rhodamine based fluorescence sensors were reported to detect metal
      ions with high sensitivity and selectivity, there are very few reports available
      to study the mechanisms of detection and the interaction between probe and metal
      ions. This paper aims to detect ferric ions by novel fluorescence chemosensors
      and study the mechanisms in detail. A novel probe AD-MAH-RhB was designed and
      synthesized from rhodamine B (RhB), adamantyl (AD), ethylene diamine and maleic
      anhydride (MAH). AD-MAH-RhB could detect Fe(3+) in aqueous solutions. The
      mechanism was explored by the HSAB principle, FTIR and mass spectra. The results
      suggested that Fe(3+) bound with amine and oxygen atoms in AD-MAH-RhB to form a
      complex composed of a 2 : 1 stoichiometry of Fe(3+) and the probe. Moreover,
      computational simulations were employed to further investigate the detection
      mechanism. The calculated results showed that Fe(3+) could conjugate with AD-MAH
      RhB probe to form a stable complex, which was induced by synergetic effects of
      the suitable space and distance of van der Waals forces. However, Hg(2+) was
      found to disturb this detection and form a complex with 1 : 2 stoichiometry of
      Hg(2+) and AD-MAH-RhB. Then, another probe, beta-cyclodextrin modified polymaleic
      anhydride (PMAH-CD) including AD-MAH-RhB (PMAH-CD/AD-MAH-RhB) was fabricated by
      inclusion interaction between CD and AD. PMAH-CD@AD-MAH-RhB showed high
      selectivity and sensitivity to Fe(3+) in the aqueous solution by eliminating the
      interruption of Hg(2+) possibly due to the high hydrogen interaction among the
      probes to inhibit the stable form complex with Hg(2+). 

PMID- 25574523
TI  - Systematic comparison between SDS-PAGE/RPLC and high-/low-pH RPLC coupled tandem
      mass spectrometry strategies in a whole proteome analysis.
AB  - SDS-PAGE and high-pH RPLC are commonly used fractionation strategies in
      proteomics research. A comparative investigation of these two strategies would be
      meaningful to thoroughly understand their respective features. Here, we
      systematically compared the two methods by trying 4 SDS-PAGE/RPLC and 3 high-/low
      pH RPLC different workflows for a higher sensitivity in protein identification.
      Totally 9793 proteins were identified in HepG2 cells, with 8581 proteins
      identified by high-/low-pH RPLC workflows and 7933 by SDS-PAGE/RPLC workflows.
      The results demonstrate that using high-pH RPLC in the first dimensional
      separation would favour a high-throughput proteome analysis but choosing SDS-PAGE
      could yield much better peptide coverage. We found that the SDS-PAGE
      fractionation method benefits the neutral pI peptides. We also analyzed
      unexpected modifications caused by the two strategies. Our results suggest that
      more pre-fractionation benefits protein identifications in both strategies and
      pooling of gel pieces according to their grey values increased the identification
      efficiency in SDS-PAGE/RPLC workflows. 

PMID- 25574524
TI  - A high-throughput screening method for determining the substrate scope of
      nitrilases.
AB  - Nitrile compounds are intermediates in the synthesis of pharmaceuticals such as
      atorvastatin. We have developed a chromogenic reagent to screen for nitrilase
      activity as an alternative to Nessler's reagent. It produces a semi-quantifiable
      blue colour and hydrolysis of 38 nitrile substrates by 23 nitrilases as cell-free
      extracts has been shown. 

PMID- 25574525
TI  - A selenium-containing ruthenium complex as a cancer radiosensitizer, rational
      design and the important role of ROS-mediated signalling.
AB  - A novel selenium-containing ruthenium complex Ru(phtpy)(phenSe)Cl(ClO4) (phtpy =
      4-phenyl-2,2':6',2''-terpyridine, phenSe = 2-selenicimidazole[4,5-f]1,10
      phenanthroline) has been synthesized and found be able to enhance radiation
      induced DNA damage through superoxide overproduction, which leads to G2/M arrest
      and apoptosis in cancer cells by activating ROS-mediated pathways. 

PMID- 25574526
TI  - A hybrid of titanium nitride and nitrogen-doped amorphous carbon supported on SiC
      as a noble metal-free electrocatalyst for oxygen reduction reaction.
AB  - A novel noble metal-free catalyst, with nitrogen-doped amorphous carbon and
      titanium nitride particles supported on SiC (NC-TiN/SiC), was synthesized. The NC
      TiN/SiC catalyst exhibited excellent oxygen reduction reaction activities as well
      as superior stability and methanol tolerance. The catalytic activities were
      attributed to the synergistic effect of TiN and NC. 

PMID- 25574527
TI  - A synthetic biology approach for the transformation of l-alpha-amino acids to the
      corresponding enantiopure (R)- or (S)-alpha-hydroxy acids.
AB  - Combinatorial assembly and variation of promoters on a single expression plasmid
      allowed the balance of the catalytic steps of a three enzyme (l-AAD, HIC, FDH)
      cascade in E. coli. The designer cell catalyst quantitatively transformed l-amino
      acids to the corresponding optically pure (R)- and (S)-alpha-hydroxy acids at up
      to 200 mM substrate concentration. 

PMID- 25574529
TI  - The Virtual Liver Network: systems understanding from bench to bedside.
AB  - Adriano Henney speaks to Hannah Coaker, Commissioning Editor. After achieving a
      PhD in medicine and spending many years in academic research in the field of
      cardiovascular disease, Adriano Henney was recruited by Zeneca Pharmaceuticals
      from a British Heart Foundation Senior Fellowship, where he led the exploration
      of new therapeutic approaches in atherosclerosis, specifically focusing on his
      research interests in vascular biology. Following the merger with Astra to form
      AstraZeneca, Henney became responsible for exploring strategic improvements to
      the company's approaches to pharmaceutical target identification and the
      reduction of attrition in early development, directing projects across research
      sites and across functional project teams in the USA, Sweden and the UK. This
      resulted in the creation of a new multidisciplinary department that focused on
      pathway mapping, modeling and simulation and supporting projects across research
      and development, which evolved into the establishment of the practice of systems
      biology within the company. Here, projects prototyped the application of
      mechanistic disease-modeling approaches in order to support the discovery of
      innovative new medicines, such as Iressa(r). Since leaving AstraZeneca, Henney
      has continued his interest in systems biology, synthetic biology and systems
      medicine through his company, Obsidian Biomedical Consulting Ltd. He now directs
      a major ?50 million German national flagship program - the Virtual Liver Network 
      which is currently the largest systems biology program in Europe.

PMID- 25574528
TI  - Determination of receptor specificities for whole influenza viruses using
      multivalent glycan arrays.
AB  - Influenza viruses bind to mucosal glycans to gain entry into a host organism and
      initiate infection. The target glycans are often displayed in multivalent
      arrangements on proteins; however, how glycan presentation influences viral
      specificity is poorly understood. Here, we report a microarray platform
      approximating native glycan display to facilitate such studies. 

PMID- 25574530
TI  - Multitarget drug discovery projects in CNS diseases: quantitative systems
      pharmacology as a possible path forward.
AB  - Clinical development in brain diseases has one of the lowest success rates in the
      pharmaceutical industry, and many promising rationally designed single-target R&D
      projects fail in expensive Phase III trials. By contrast, successful older CNS
      drugs do have a rich pharmacology. This article will provide arguments suggesting
      that highly selective single-target drugs are not sufficiently powerful to
      restore complex neuronal circuit homeostasis. A rationally designed multitarget
      project can be derisked by dialing in an additional symptomatic treatment effect
      on top of a disease modification target. Alternatively, we expand upon a
      hypothetical workflow example using a humanized computer-based quantitative
      systems pharmacology platform. The hope is that incorporating rationally
      multipharmacology drug discovery could potentially lead to more impactful
      polypharmacy drugs.

PMID- 25574531
TI  - Cancer cell metabolism as new targets for novel designed therapies.
AB  - Metabolic processes are altered in cancer cells, which obtain advantages from
      this metabolic reprogramming in terms of energy production and synthesis of
      biomolecules that sustain their uncontrolled proliferation. Due to the conceptual
      progresses in the last decade, metabolic reprogramming was recently included as
      one of the new hallmarks of cancer. The advent of high-throughput technologies to
      amass an abundance of omic data, together with the development of new
      computational methods that allow the integration and analysis of omic data by
      using genome-scale reconstructions of human metabolism, have increased and
      accelerated the discovery and development of anticancer drugs and tumor-specific
      metabolic biomarkers. Here we review and discuss the latest advances in the
      context of metabolic reprogramming and the future in cancer research.

PMID- 25574532
TI  - We know in part: James McCosh on evolution and Christian faith.
AB  - James McCosh (1811-1894), president of Princeton College from 1868 to 1888,
      played a significant role in the American reception of evolution in the late
      1800s - he was one of the more prominent clergyman to assuage the public's fears
      of evolution while incorporating evolution into a conservative Christian
      worldview. McCosh was a prolific writer, whose books document his intellectual
      journey from hostility to acceptance of evolution. Three things will stand out in
      this overview that have not been emphasized in detail in other works: (1) James
      McCosh's perspective on evolution dramatically changed over time; (2) McCosh's
      motivations for engaging in the evolution-religion debate serve to clear up
      confusion regarding McCosh's final position on evolution; and (3) the theological
      and philosophical basis for McCosh's acceptance of evolution was established
      while McCosh was still hostile to evolution. His theological background therefore
      'pre-adapted' him for evolution, and he was able to preach theology and evolution
      without substantially altering his theology.

PMID- 25574533
TI  - Immune balance: the development of the idea and its applications.
AB  - It has long been taken for granted that the immune system's capacity to protect
      an individual from infection and disease depends on the power of the system to
      distinguish between self and nonself. However, accumulating data have undermined
      this fundamental concept. Evidence against the self/nonself discrimination model
      left researchers in need of a new overarching framework able to capture the
      immune system's reactivity. Here, I highlight that along with the self/nonself
      model, another powerful representation of the immune system's reactivity has been
      developed in the twentieth century immunology. According to this alternative
      view, the immune system is not a killer of nonself strangers but a peace-maker
      helping to establish harmony with the environment. The balance view of the system
      has never become part of the dominant paradigm. However, it is gaining more and
      more currency as new research develops. Advances in mucosal immunology confirm
      that instead of distinguishing between self and foreign the immune system reacts
      to microbial, chemical and self-induced alterations to produce responses that
      counterbalance effects of these changes.

PMID- 25574535
TI  - Stretching the boundaries of extracellular matrix research.
AB  - Extracellular matrix (ECM) proteins constitute >1% of the proteome and interact
      with many modifiers and growth factors to affect most aspects of cellular
      behaviour during development and normal physiology, as well as in diseases such
      as fibroses, cancer and many genetic disorders. In addition to biochemical
      signals provided to cells by ECM proteins, important cell-ECM interactions
      involve bidirectional mechanotransduction influences, which are dependent on the
      physical structure and organization of the ECM. These are beginning to be
      understood using twenty-first-century approaches, including biophysics,
      nanotechnology, biological engineering and modern microscopy. Articles in this
      issue of Nature Reviews Molecular Cell Biology review progress in our
      understanding of the ECM.

PMID- 25574534
TI  - The long and winding road of molecular data in phylogenetic analysis.
AB  - The use of molecules and reactions as evidence, markers and/or traits for
      evolutionary processes has a history more than a century long. Molecules have
      been used in studies of intra-specific variation and studies of similarity among
      species that do not necessarily result in the analysis of phylogenetic relations.
      Promoters of the use of molecular data have sustained the need for quantification
      as the main argument to make use of them. Moreover, quantification has allowed
      intensive statistical analysis, as a condition and a product of increasing
      automation. All of these analyses are subject to the methodological anxiety
      characteristic of a community in search of objectivity (Suarez-Diaz and Anaya
      Munoz, Stud Hist Philos Biol Biomed Sci 39:451-458, 2008). It is in this context
      that scientists compared and evaluated protein and nucleic acid sequence data
      with other types of molecular data - including immunological, electrophoretic and
      hybridization data. This paper argues that by looking at longterm historical
      processes, such as the use of molecular evidence in evolutionary biology, we gain
      valuable insights into the history of science. In that sense, it accompanies a
      growing concern among historians for big-pictures of science that incorporate the
      fruitful historical research on local cases of the last decades.

PMID- 25574536
TI  - Outreach: Speak up for science.

PMID- 25574537
TI  - Serum 25-hydroxyvitamin D levels in patients with atopic eczema and the influence
      of narrowband ultraviolet B phototherapy.
AB  - BACKGROUND: Narrowband ultraviolet B phototherapy (nbUVB) is an established
      treatment modality for patients with severe atopic dermatitis (AD) and is known
      to increase serum vitamin D levels (SVD). The relationship between SVD and AD
      remains unclear. OBJECTIVES: To assess SVD and disease severity in patients with
      AD before and after nbUVB and establish whether a change in SVD correlates to
      response to nbUVB. Methods: A single-centre, open observational study recruited
      21 male and 17 female patients with AD between November and April. Eczema
      severity was measured using the SCORAD tool, and serum 25-hydroxyvitamin D3
      levels were determined before and after nbUVB, which was administered thrice
      weekly. RESULTS: Nine patients had severe AD, 23 moderate and six mild, as
      indicated by SCORAD measurements. Seventeen patients completed the study. Median
      SVD increased from 45 nmol/l pre-treatment to 169 nmol/l post-treatment (95% CI
      2.9-5.0 times baseline) (P < 0.0001). Mean SCORAD reduction following nbUVB was
      significant at 21.9 units (95% CI, 14.9-28.9) (P < 0.0001). No evidence of a
      relationship between change in SCORAD and change in SVD was found. LIMITATIONS: A
      significant number of patients failed to complete the study. CONCLUSIONS:
      Patients with AD are at risk of vitamin D deficiency. Correlation between this
      and disease severity has been postulated, but this study does not provide
      confirmatory evidence.

PMID- 25574538
TI  - [Do we need advice created by political advisors].

PMID- 25574539
TI  - [Bullying at work -- what are my rights? ].

PMID- 25574540
TI  - [When the workplace becomes hell -- causes and effects of bullying].

PMID- 25574541
TI  - Author response.

PMID- 25574542
TI  - Author response.

PMID- 25574543
TI  - Acute neurologic illness of unknown etiology in children- Colorado, August
      September 2014.

PMID- 25574544
TI  - Ebola drug trials to be fast- tracked in West Africa.

PMID- 25574545
TI  - Ever-present endemic Ebola now major concern for disease experts.

PMID- 25574546
TI  - Reeling from Ebola, WHO warns of MERS risk to Africa.

PMID- 25574547
TI  - After the "blood diamond" conflict: lassa fever in Sierra Leone.

PMID- 25574548
TI  - One case of malaria, 4 Plasmodium species.

PMID- 25574549
TI  - Protothecosis: a lethal infection due to an achlorophylous algae.

PMID- 25574550
TI  - Visceral Leishmaniasis as a complication of tumor necrosis factor inhibitor
      therapy.

PMID- 25574551
TI  - Rapidly fatal cerebral Acanthamoeba infection after total artificial heart
      implantation.

PMID- 25574552
TI  - Jaundice? Yes, there is an app for that.

PMID- 25574553
TI  - A new frontier: cell-based therapy.

PMID- 25574554
TI  - Gloving for all patient contact?

PMID- 25574555
TI  - Single-use only syringes by 2017.

PMID- 25574556
TI  - Coaching parents through the home stretch.

PMID- 25574557
TI  - New features of systemic vasculitides.

PMID- 25574558
TI  - Central-line infections--author's response.

PMID- 25574559
TI  - Biography--Rakesh Kumar, Ph.D.

PMID- 25574560
TI  - Patient education. Spelunking for cancer.

PMID- 25574561
TI  - Synthesis and properties of the strained alkene perfluorobicyclo[2.2.0]hex-1(4)
      ene.
AB  - The title fluoroalkene has been generated by dehalogenation of dibromide and
      diiodide precursors and trapped in situ. retro-Diels-Alder reaction of its adduct
      with N-benzylpyrrole has made the alkene available in high yield and purity. In
      sharp contrast to its extremely labile hydrocarbon counterpart, the fluoroalkene
      is very stable yet highly reactive. Its characterization includes its electron
      affinity, photoelectron spectrum, and the previously reported structure
      determination by electron diffraction. 

PMID- 25574562
TI  - Investigation of anion-pi interactions involving thiophene walls incorporated
      calix[4]pyrroles.
AB  - Thiophene containing "two-wall" aryl extended calix[4]pyrroles were synthesized
      for the first time, through acid catalyzed condensation of 2-acetylthiophenes
      with pyrrole. Isomeric "two-walled" calix[4]pyrroles (8a-10a and 8b-10b) were
      obtained in satisfactory yields and their halide anion binding strengths were
      investigated in the solution phase by (1)H NMR and in the gas phase by
      computational methods and mass spectrometry. Change in the chemical shifts of
      thiophene -CH-protons during the course of NMR titrations entailed participation
      of the thiophene rings in anion binding; this fact was further substantiated by
      computational methods. The alpha,alpha-(cis)-isomers (8a, 9a, and 10a) showed
      strong binding toward F(-) and Cl(-) anions when compared to their isomeric
      alpha,beta-(trans)-isomer (8b, 9b, and 10b). In both isomers, binding with F(-)
      anion was found to be stronger than that with Cl(-) anion. Both the solution
      phase and gas-phase results revealed that the thiophene rings stabilize the
      anions through anion-pi interactions. 

PMID- 25574563
TI  - Hydrated silica exterior produced by biomimetic silicification confers viral
      vaccine heat-resistance.
AB  - Heat-lability is a key roadblock that strangles the widespread applications of
      many biological products. In nature, archaeal and extremophilic organisms utilize
      amorphous silica as a protective biomineral and exhibit considerable thermal
      tolerance. Here we present a bioinspired approach to generate thermostable virus
      by introducing an artificial hydrated silica exterior on individual virion.
      Similar to thermophiles, silicified viruses can survive longer at high
      temperature than their wild-type relatives. Virus inactivation assays showed that
      silica hydration exterior of the modified virus effectively prolonged infectivity
      of viruses by ~ 10-fold at room temperature, achieving a similar result as that
      obtained by storing native ones at 4  degrees C. Mechanistic studies indicate
      that amorphous silica nanoclusters stabilize the inner virion structure by
      forming a layer that restricts molecular mobility, acting as physiochemical
      nanoanchors. Notably, we further evaluate the potential application of this
      biomimetic strategy in stabilizing clinically approved vaccine, and the
      silicified polio vaccine that can retain 90% potency after the storage at room
      temperature for 35 days was generated by this biosilicification approach and
      validated with in vivo experiments. This approach not only biomimetically
      connects inorganic material and living virus but also provides an innovative
      resolution to improve the thermal stability of biological agents using
      nanomaterials.

PMID- 25574564
TI  - Ex post facto assessment of diffusion tensor imaging metrics from different MRI
      protocols: preparing for multicentre studies in ALS.
AB  - Diffusion tensor imaging (DTI) for assessing ALS-associated white matter
      alterations has still not reached the level of a neuroimaging biomarker. Since
      large-scale multicentre DTI studies in ALS may be hampered by differences in
      scanning protocols, an approach for pooling of DTI data acquired with different
      protocols was investigated. Three hundred and nine datasets from 170 ALS patients
      and 139 controls were collected ex post facto from a monocentric database
      reflecting different scanning protocols. A 3D correction algorithm was introduced
      for a combined analysis of DTI metrics despite different acquisition protocols,
      with the focus on the CST as the tract correlate of ALS neuropathological stage
      1. A homogenous set of data was obtained by application of 3D correction
      matrices. Results showed that a fractional anisotropy (FA) threshold of 0.41
      could be defined to discriminate ALS patients from controls
      (sensitivity/specificity, 74%/72%). For the remaining test sample,
      sensitivity/specificity values of 68%/74% were obtained. In conclusion, the
      objective was to merge data recorded with different DTI protocols with 3D
      correction matrices for analyses at group level. These post processing tools
      might facilitate analysis of large study samples in a multicentre setting for DTI
      analysis at group level to aid in establishing DTI as a non-invasive biomarker
      for ALS. 

PMID- 25574565
TI  - Letter to the editor: Deep venous thrombosis and pulmonary embolism.

PMID- 25574566
TI  - A noninvasive estimation of cerebral perfusion pressure using critical closing
      pressure.
AB  - OBJECT: Cerebral blood flow is associated with cerebral perfusion pressure (CPP),
      which is clinically monitored through arterial blood pressure (ABP) and invasive
      measurements of intracranial pressure (ICP). Based on critical closing pressure
      (CrCP), the authors introduce a novel method for a noninvasive estimator of CPP
      (eCPP). METHODS: Data from 280 head-injured patients with ABP, ICP, and
      transcranial Doppler ultrasonography measurements were retrospectively examined.
      CrCP was calculated with a noninvasive version of the cerebrovascular impedance
      method. The eCPP was refined with a predictive regression model of CrCP-based
      estimation of ICP from known ICP using data from 232 patients, and validated with
      data from the remaining 48 patients. RESULTS: Cohort analysis showed eCPP to be
      correlated with measured CPP (R = 0.851, p < 0.001), with a mean +/- SD
      difference of 4.02 +/- 6.01 mm Hg, and 83.3% of the cases with an estimation
      error below 10 mm Hg. eCPP accurately predicted low CPP (< 70 mm Hg) with an area
      under the curve of 0.913 (95% CI 0.883-0.944). When each recording session of a
      patient was assessed individually, eCPP could predict CPP with a 95% CI of the SD
      for estimating CPP between multiple recording sessions of 1.89-5.01 mm Hg.
      CONCLUSIONS: Overall, CrCP-based eCPP was strongly correlated with invasive CPP,
      with sensitivity and specificity for detection of low CPP that show promise for
      clinical use.

PMID- 25574567
TI  - Impact of resident participation on morbidity and mortality in neurosurgical
      procedures: an analysis of 16,098 patients.
AB  - OBJECT: The authors sought to determine the impact of resident participation on
      overall 30-day morbidity and mortality following neurosurgical procedures.
      METHODS: The American College of Surgeons National Surgical Quality Improvement
      Program database was queried for all patients who had undergone neurosurgical
      procedures between 2006 and 2012. The operating surgeon(s), whether an attending
      only or attending plus resident, was assessed for his or her influence on
      morbidity and mortality. Multivariate logistic regression, was used to estimate
      odds ratios for 30-day postoperative morbidity and mortality outcomes for the
      attending-only compared with the attending plus resident cohorts (attending group
      and attending+resident group, respectively). RESULTS: The study population
      consisted of 16,098 patients who had undergone elective or emergent neurosurgical
      procedures. The mean patient age was 56.8 +/- 15.0 years, and 49.8% of patients
      were women. Overall, 15.8% of all patients had at least one postoperative
      complication. The attending+resident group demonstrated a complication rate of
      20.12%, while patients with an attending-only surgeon had a statistically
      significantly lower complication rate at 11.70% (p < 0.001). In the total
      population, 263 patients (1.63%) died within 30 days of surgery. Stratified by
      operating surgeon status, 162 patients (2.07%) in the attending+resident group
      died versus 101 (1.22%) in the attending group, which was statistically
      significant (p < 0.001). Regression analyses compared patients who had resident
      participation to those with only attending surgeons, the referent group.
      Following adjustment for preoperative patient characteristics and comorbidities,
      multivariate regression analysis demonstrated that patients with resident
      participation in their surgery had the same odds of 30-day morbidity (OR = 1.05,
      95% CI 0.94-1.17) and mortality (OR = 0.92, 95% CI 0.66-1.28) as their attending
      only counterparts. CONCLUSIONS: Cases with resident participation had higher
      rates of mortality and morbidity; however, these cases also involved patients
      with more comorbidities initially. On multivariate analysis, resident
      participation was not an independent risk factor for postoperative 30-day
      morbidity or mortality following elective or emergent neurosurgical procedures.

PMID- 25574568
TI  - The utility of preoperative diffusion tensor imaging in the surgical management
      of brainstem cavernous malformations.
AB  - OBJECT: Resection of brainstem cavernous malformations (BSCMs) may reduce the
      risk of stepwise neurological deterioration secondary to hemorrhage, but the
      morbidity of surgery remains high. Diffusion tensor imaging (DTI) and diffusion
      tensor tractography (DTT) are neuroimaging techniques that may assist in the
      complex surgical planning necessary for these lesions. The authors evaluate the
      utility of preoperative DTI and DTT in the surgical management of BSCMs and their
      correlation with functional outcome. METHODS: A retrospective review was
      conducted to identify patients who underwent resection of a BSCM between 2007 and
      2012. All patients had preoperative DTI/DTT studies and a minimum of 6 months of
      clinical and radiographic follow-up. Five major fiber tracts were evaluated
      preoperatively using the DTI/DTT protocol: 1) corticospinal tract, 2) medial
      lemniscus and medial longitudinal fasciculus, 3) inferior cerebellar peduncle, 4)
      middle cerebellar peduncle, and 5) superior cerebellar peduncle. Scores were
      applied according to the degree of distortion seen, and the sum of scores was
      used for analysis. Functional outcomes were measured at hospital admission,
      discharge, and last clinic visit using modified Rankin Scale (mRS) scores.
      RESULTS: Eleven patients who underwent resection of a BSCM and preoperative DTI
      were identified. The mean age at presentation was 49 years, with a male-to-female
      ratio of 1.75:1. Cranial nerve deficit was the most common presenting symptom
      (81.8%), followed by cerebellar signs or gait/balance difficulties (54.5%) and
      hemibody anesthesia (27.2%). The majority of the lesions were located within the
      pons (54.5%). The mean diameter and estimated volume of lesions were 1.21 cm and
      1.93 cm(3), respectively. Using DTI and DTT, 9 patients (82%) were found to have
      involvement of 2 or more major fiber tracts; the corticospinal tract and medial
      lemniscus/medial longitudinal fasciculus were the most commonly affected. In 2
      patients with BSCMs without pial presentation, DTI/DTT findings were important in
      the selection of the surgical approach. In 2 other patients, the results from
      preoperative DTI/DTT were important for selection of brainstem entry zones. All
      11 patients underwent gross-total resection of their BSCMs. After a mean
      postoperative follow-up duration of 32.04 months, all 11 patients had excellent
      or good outcome (mRS Score 0-3) at the time of last outpatient clinic evaluation.
      DTI score did not correlate with long-term outcome. CONCLUSIONS: Preoperative DTI
      and DTT should be considered in the resection of symptomatic BSCMs. These imaging
      studies may influence the selection of surgical approach or brainstem entry
      zones, especially in deep-seated lesions without pial or ependymal presentation.
      DTI/DTT findings may allow for more aggressive management of lesions previously
      considered surgically inaccessible. Preoperative DTI/DTT changes do not appear to
      correlate with functional postoperative outcome in long-term follow-up.

PMID- 25574569
TI  - Fatal rupture of a brain arteriovenous malformation flow-related aneurysm during
      microcatheter removal: a rare complication.
AB  - Intracranial aneurysms are relatively frequently encountered in patients with
      brain arteriovenous malformations (BAVMs). They may be located on the circle of
      Willis, on arterial feeders, or even inside the nidus. Because BAVM-associated
      aneurysms represent a risk factor of bleeding, the question of the timing and
      modality of their management remains a matter of debate in unruptured BAVMs. The
      authors present a case of fatal periprocedural rupture of a flow-related aneurysm
      (FRA) during the removal of the microcatheter after injection of a liquid embolic
      agent. A 40-year-old man was treated at the authors' institution for the
      management of a Spetzler-Martin Grade III left unruptured frontal BAVM, revealed
      by seizures and a focal neurological deficit attributed to flow steal phenomenon.
      After a multidisciplinary meeting, endovascular treatment was considered to
      reduce the flow of the BAVM. A proximal FRA located on the feeding internal
      carotid artery (ICA) was purposely left untreated because it did not meet the
      criteria of the authors' institution for preventative treatment (i.e., small size
      [2.5 mm]). During embolization, at the time of microcatheter retrieval, and after
      glue injection, the aneurysm unexpectedly ruptured. The aneurysm's rupture was
      attributed to the stress (torsion/flexion) on the ICA caused by the microcatheter
      removal. Despite the attempts to manage the bleeding, the patient eventually died
      of the acute increase of intracranial pressure related to the massive
      subarachnoid hemorrhage. This case highlights a previously unreported mechanism
      of FRA rupture during BAVM embolization: the stress transmitted to the parent
      artery during the removal of the microcatheter. 

PMID- 25574570
TI  - Neurosurgical decision making: personal and professional preferences.
AB  - OBJECT: Physicians are often solicited by patients or colleagues for clinical
      recommendations they would make for themselves if faced by a clinical situation.
      The act of making a recommendation can alter the clinical course being taken. The
      authors sought to understand this dynamic across different neurosurgical
      scenarios by examining how neurosurgeons value the procedures that they offer.
      METHODS: The authors conducted an online survey using the Congress of
      Neurological Surgeons listserv in May 2013. Respondents were randomized to answer
      either as the surgeon or as the patient. Questions encompassed an array of
      distinct neurosurgical scenarios. Data on practice parameters and experience
      levels were also collected. RESULTS: Of the 534 survey responses, 279 responded
      as the "neurosurgeon" and 255 as the "patient." For both vestibular schwannoma
      and arteriovenous malformation management, more respondents chose resection for
      their patient but radiosurgery for themselves (p = 0.002 and p = 0.001,
      respectively). Aneurysm coiling was chosen more often than clipping, but those
      whose practice was >= 30% open cerebrovascular neurosurgery were less likely to
      choose coiling. Overall, neurosurgeons who focus predominantly on tumors were
      more aggressive in managing the glioma, vestibular schwannoma, arteriovenous
      malformation, and trauma. Neurosurgeons more than 10 years out of residency were
      less likely to recommend surgery for management of spinal pain, aneurysm,
      arteriovenous malformation, and trauma scenarios. CONCLUSIONS: In the majority of
      cases, altering the role of the surgeon did not change the decision to pursue
      treatment. In certain clinical scenarios, however, neurosurgeons chose treatment
      options for themselves that were different from what they would have chosen for
      (or recommended to) their patients. For the management of vestibular schwannomas,
      arteriovenous malformations, intracranial aneurysms, and hypertensive
      hemorrhages, responses favored less invasive interventions when the surgeon was
      the patient. These findings are likely a result of cognitive biases, previous
      training, experience, areas of expertise, and personal values.

PMID- 25574571
TI  - Emergent intracranial surgical embolectomy in conjunction with carotid
      endarterectomy for acute internal carotid artery terminus embolic occlusion and
      tandem occlusion of the cervical carotid artery due to plaque rupture.
AB  - Acute internal carotid artery (ICA) terminus occlusion is associated with
      extremely poor functional outcomes or mortality, especially when it is caused by
      plaque rupture of the cervical ICA with engrafted thrombus that elongates and
      extends into the ICA terminus. The goal of this study was to evaluate the
      efficacy and safety of surgical embolectomy in conjunction with carotid
      endarterectomy (CEA) for acute ICA terminus occlusion associated with cervical
      plaque rupture resulting in tandem occlusion. A retrospective review of medical
      records was performed. Clinical and radiographic characteristics were evaluated,
      including details of surgical technique, recanalization grade, recanalization
      time, complications, modified Rankin Scale (mRS) score at 3 months, and National
      Institutes of Health Stroke Scale (NIHSS) score improvement at 1 month. Three
      patients (mean age 77.3 years; median presenting NIHSS Score 22, range 19-26)
      presented with abrupt tandem occlusion of the cervical ICA and ICA terminus and
      were selected for surgery after confirmation of embolic high-density signal at
      the ICA terminus on CT and diffusion-weighted imaging (DWI)/magnetic resonance
      angiography (MRA) mismatch. All patients underwent craniotomy for surgical
      embolectomy of the ICA terminus embolus followed by cervical exposure, aspiration
      of long residual proximal embolus ranging from the cervical to cavernous ICA, and
      removal of ruptured unstable plaque by CEA. Postoperative MRA demonstrated
      Thrombolysis In Myocardial Infarction (TIMI) 3 recanalization in all patients
      (100%) without evidence of additional infarction according to DWI. Mean
      recanalization time from hospital arrival was 234 minutes and from start of
      surgery, 151 minutes. Serial postoperative CT and MRI studies showed no
      symptomatic hemorrhage, brain edema, or progression of infarction. The patients'
      mRS scores at 3 months were 3, 3, and 1. All 3 patients demonstrated marked
      improvements in NIHSS scores (median 17 points; range 13-23 points) at 1 month.
      Considering the dismal prognosis associated with ICA terminus occlusion,
      especially when accompanied by cervical plaque rupture, emergent surgical
      embolectomy in conjunction with CEA might be an effective and decisive treatment
      option with a high complete recanalization rate and acceptable safety profile.

PMID- 25574572
TI  - Seasonal variability in the incidence of carcinomatous meningitis.
AB  - OBJECT: The aim of the study was to investigate whether there are seasonal
      differences in the occurrence of carcinomatous meningitis (CM), with a greater
      prevalence of the disease in months with higher temperatures. METHODS: The
      authors searched the records of all patients with a diagnosis of CM from 1998
      until 2013 at the University Hospital of Patras, Greece. The date of
      hospitalization was extracted for each patient. The cases were divided into 2
      categories depending on the time of CM diagnosis. Based on the official data
      regarding the annual temperature distribution in this region, the authors divided
      the patients into 2 groups. The first group consisted of cases diagnosed with CM
      from October 15 to April 15 (cold climate and shorter daytime duration), whereas
      the second group comprised patients diagnosed between April 15 and October 15
      (warm climate and longer daytime duration). RESULTS: Overall, 44 confirmed cases
      of CM were found. The most common type of malignancy associated with the
      development of CM was breast cancer (27 patients), while the second most common
      tumor was lung carcinoma (11 patients). The median interval between the time of
      initial cancer diagnosis and CM was 4.5 years. Thirty-one patients were diagnosed
      with CM during the period between April 15 and October 15, while the remaining 13
      patients developed CM between October 15 and April 15, a significant difference
      (p = 0.01). CONCLUSIONS: Significantly more patients developed CM during the warm
      season of the year. To the authors' knowledge, this is the first study to provide
      evidence for the potential seasonal variability in CM incidence. However, these
      results should be validated prospectively in larger cohorts.

PMID- 25574573
TI  - Julius Caesar Arantius (Giulio Cesare Aranzi, 1530-1589) and the hippocampus of
      the human brain: history behind the discovery.
AB  - Julius Caesar Arantius is one of the pioneer anatomists and surgeons of the 16th
      century who discovered the different anatomical structures of the human body. One
      of his prominent discoveries is the hippocampus. At that time, Arantius
      originated the term hippocampus, from the Greek word for seahorse (hippos
      ["horse"] and kampos ["sea monster"]). Arantius published his description of the
      hippocampus in 1587, in the first chapter of his work titled De Humano Foetu
      Liber. Numerous nomenclatures of this structure, including "white silkworm,"
      "Ammon's horn," and "ram's horn" were proposed by different scholars at that
      time. However, the term hippocampus has become the most widely used in the
      literature. 

PMID- 25574574
TI  - Integrated microfluidic chip and online SCX separation allows untargeted
      nanoscale metabolomic and peptidomic profiling.
AB  - Metabolomics and peptidomics are systems biology approaches in which broad
      populations of molecular species produced in a cell or tissue sample are
      identified and quantified. These two molecular populations, metabolites and
      peptides, can be extracted from tissues in a similar fashion, and we therefore
      have here developed an integrated platform for their extraction and
      characterization. This was accomplished by liquid-liquid extraction of peptides
      and metabolites from tissue samples and online strong cation exchange (SCX)
      separation to allow characterization of each population individually. The
      platform was validated both by a mixed set of purified standards and by an
      analysis of splenic tissue from SIV-infected macaques, showing both good
      reproducibility in chromatography, with relative standard deviation (RSD) of hold
      time less than 0.4%, and clear separation of charge state, with ~ 95% of
      molecular features in SCX separated runs at charge states of +1 or +2. Finally,
      we used this platform to analyze the physiological response to infection in the
      spleen, showing that the spleen contains an abundance of hemoglobin-derived
      peptides, which do not appear to change in response to infection, and that there
      appears to be a large and variable metabolic response to infection. We therefore
      present a method for peptidomic and metabolomic profiling which is simple,
      robust, and easy to implement.

PMID- 25574575
TI  - Square-antiprismatic eight-coordinate complexes of divalent first-row transition
      metal cations: a density functional theory exploration of the electronic
      structural landscape.
AB  - Density functional theory (in the form of the PW91, BP86, OLYP, and B3LYP
      exchange-correlation functionals) has been used to map out the low-energy states
      of a series of eight-coordinate square-antiprismatic (D2d) first-row transition
      metal complexes, involving Mn(II), Fe(II), Co(II), Ni(II), and Cu(II), along with
      a pair of tetradentate N4 ligands. Of the five complexes, the Mn(II) and Fe(II)
      complexes have been synthesized and characterized structurally and
      spectroscopically, whereas the other three are as yet unknown. Each N4 ligand
      consists of a pair of terminal imidazole units linked by an o-phenylenediimine
      unit. The imidazole units are the strongest ligands in these complexes and
      dictate the spatial disposition of the metal three-dimensional orbitals. Thus,
      the dx(2)-y(2) orbital, whose lobes point directly at the coordinating imidazole
      nitrogens, has the highest orbital energy among the five d orbitals, whereas the
      dxy orbital has the lowest orbital energy. In general, the following orbital
      ordering (in order of increasing orbital energy) was found to be operative: dxy <
      dxz = dyz <= dz(2) < dx(2)-y(2). The square-antiprism geometry does not lead to
      large energy gaps between the d orbitals, which leads to an S = 2 ground state
      for the Fe(II) complex. Nevertheless, the dxy orbital has significantly lower
      energy relative to that of the dxz and dyz orbitals. Accordingly, the ground
      state of the Fe(II) complex corresponds unambiguously to a
      dxy(2)dxz(1)dyz(1)dz(2)(1)dx(2)-y(2)(1) electronic configuration. Unsurprisingly,
      the Mn(II) complex has an S = 5/2 ground state and no low-energy d-d excited
      states within 1.0 eV of the ground state. The Co(II) complex, on the other hand,
      has both a low-lying S = 1/2 state and multiple low-energy S = 3/2 states. Very
      long metal-nitrogen bonds are predicted for the Ni(II) and Cu(II) complexes;
      these bonds may be too fragile to survive in solution or in the solid state, and
      the complexes may therefore not be isolable. Overall, the different exchange
      correlation functionals provided a qualitatively consistent and plausible picture
      of the low-energy d-d excited states of the complexes. 

PMID- 25574576
TI  - Effects of relaxation interventions on depression and anxiety among older adults:
      a systematic review.
AB  - OBJECTIVES: This systematic review examined empirical evidence of the effects of
      relaxation interventions on anxiety and depression among older adults. METHOD: A
      comprehensive literature search identified studies that satisfied the pre-set
      inclusion and exclusion criteria. We focused on 15 published and non-published
      studies - 12 randomised controlled trials and three non-randomised controlled
      trials - undertaken in the past 20 years (1994-2014). Three reviewers selected
      studies, extracted data, and appraised the methodological quality. We then
      computed Hedges' effect sizes and used these to represent the effects of
      intervention. RESULTS: Our findings suggested that older adults who received
      relaxation interventions experienced greater reductions in depression and anxiety
      than controls in most studies. Progressive muscle relaxation training, music
      intervention, and yoga had the strongest intervention effects on depression.
      Music intervention, yoga, and combined relaxation training most effectively
      reduced anxiety symptoms among older adults. Furthermore, the impact of some
      relaxation interventions remained in effect for between 14 and 24 weeks after the
      interventions. CONCLUSION: This systematic review supported the positive effects
      of relaxation interventions on depression and anxiety among older adults. Health
      care providers may integrate relaxation interventions into standard care for
      older adults in community and hospital settings, taking into consideration the
      participant's preference and health care policy.

PMID- 25574577
TI  - Application of Liposomes in Some Dairy Products.
AB  - The application of liposomes as potential carriers to deliver food components is
      considerably an innovative technology. While the application of liposome
      technology has been very limited to date, researches indicating the potential of
      liposomes for improving the flavor of ripened cheese using accelerated methods,
      the targeted delivery of functional food ingredients, the synergistic delivery of
      ascorbic acid and tocopherols for promoting antioxidant activity in foods, and
      the stabilization of minerals (such as iron) in milk have been performed. In the
      food industry, liposomes and nanoliposomes have been employed to encapsulate
      flavoring and nutritive agents, and also, they have been suitable candidates to
      deliver antimicrobials. In this paper, application of lipase, proteinase, nisin,
      and flavor-containing liposomes in products during the processing (such as cheese
      maturity) as well as the application of liposomes-encapsulated micronutrients
      (such as iron) in milk are reviewed. 

PMID- 25574578
TI  - Polarized light absorption in wurtzite InP nanowire ensembles.
AB  - We investigate the absorption properties of ensembles of wurtzite (WZ) InP
      nanowires (NWs) by high-resolution polarization-resolved photoluminescence
      excitation (PLE) spectroscopy at T = 10 K. The degree of linear polarization of
      absorbed light, rho(abs), resulting from the PLE spectra is governed by a
      competition between the dielectric mismatch effect and the WZ selection rules
      acting differently on different optical transitions. These two contributions are
      deconvoluted with the help of finite-difference time-domain simulations, thus
      providing information about the symmetry of the three highest valence bands (A,
      B, and C) of WZ InP and the extent of the spin-orbit interaction on these states.
      Moreover, rho(abs) shows two characteristic dips corresponding to the two sharp A
      and B exciton resonances in the PLE spectra. A model developed for the dip in A
      provides the first experimental evidence of an enhancement in the dielectric
      mismatch effect originating from the Coulomb interaction between electron and
      hole.

PMID- 25574579
TI  - Infrared predissociation vibrational spectroscopy of Li+(H2O)(3-4)Ar(0,1)
      reanalyzed using density functional theory molecular dynamics.
AB  - The experimental IR-PD (infrared predissociation) spectra of Li(+)(H2O)(3-4)Ar
      and Li(+)(H2O)(3-4) clusters, monitoring two different loss channels and thus
      different temperatures, have been reanalyzed using DFT-MD (density functional
      theory based molecular dynamics) simulations for finite temperature and
      anharmonic theoretical spectroscopy. The use of DFT-MD to calculate IR-PD spectra
      at low and elevated temperatures was found remarkably accurate and useful in
      precise structural characterization. The dynamical spectra have in particular
      provided the opportunity to estimate the clusters temperatures in the IR-PD
      experiments. The temperatures for Li(+)(H2O)(3-4)Ar are estimated at 50-60 K
      whereas Li(+)(H2O)3 and Li(+)(H2O)4 have been estimated at around 500-600 and 400
      K, respectively.

PMID- 25574580
TI  - Isolation and Characterization of a Secoiridoid Derivative from Two-Phase Olive
      Waste (Alperujo).
AB  - A secoiridoid derivative was isolated from the ethyl acetate extract of two-phase
      olive waste (alperujo). The structure of this compound was fully characterized as
      s-trans-(E)-3-(1-oxobut-2-en-2-yl)glutaric acid. The spectroscopic data,
      including one- and two-dimensional nuclear magnetic resonance, mass spectrometry,
      infrared analysis, and ultraviolet spectrum, were showed. The origin of this
      compound has not been previously studied, although it most likely results from
      the breakdown of the oleuropein (or ligstroside) secoiridoid skeleton via
      oxidation and decarboxylation of the dialdehydic form of elenolic acid, with this
      transformation being enhanced by extraction of phenolics with ethyl acetate. In
      addition, the bactericidal activity of (E)-3-(1-oxobut-2-en-2-yl)glutaric acid
      and extracts containing it was evaluated against two phytopatoghenic
      microorganisms Pseudomonas syringae and Agrobacterium tumefaciens.

PMID- 25574582
TI  - Virulence and pathogenicity of Candida albicans is enhanced in biofilms
      containing oral bacteria.
AB  - This study examined the influence of bacteria on the virulence and pathogenicity
      of candidal biofilms. Mature biofilms (Candida albicans-only, bacteria-only, C.
      albicans with bacteria) were generated on acrylic and either analysed directly,
      or used to infect a reconstituted human oral epithelium (RHOE). Analyses included
      Candida hyphae enumeration and assessment of Candida virulence gene expression.
      Lactate dehydrogenase (LDH) activity and Candida tissue invasion following
      biofilm infection of the RHOE were also measured. Candida hyphae were more
      prevalent (p < 0.05) in acrylic biofilms also containing bacteria, with genes
      encoding secreted aspartyl-proteinases (SAP4/SAP6) and hyphal-wall protein (HWP1)
      up-regulated (p < 0.05). Candida adhesin genes (ALS3/EPA1), SAP6 and HWP1 were up
      regulated in mixed-species biofilm infections of RHOE. Multi-species infections
      exhibited higher hyphal proportions (p < 0.05), up-regulation of IL-18, higher
      LDH activity and tissue invasion. As the presence of bacteria in acrylic biofilms
      promoted Candida virulence, consideration should be given to the bacterial
      component when managing denture biofilm associated candidoses. 

PMID- 25574581
TI  - Psychosocial correlates of appointment keeping in immigrant cancer patients.
AB  - This study aims to determine the psychosocial correlates of self-reported
      adherence to cancer treatment appointments and treatment delays and
      interruptions. The sample included 622 immigrant cancer patients from New York
      City. Patients completed a survey that included sociodemographic and health
      related questions, questions assessing missed appointments and delays/or
      interruptions, and quality of life and depression scales. After controlling for
      sociodemographic characteristics, having a positive depression screen and poor
      physical and emotional well-being were significant predictors of missed
      appointments and delays and/or interruptions of treatment. Non-adherence to
      treatment appointments in immigrant cancer patients is a complex outcome related
      to important modifiable or treatable factors. 

PMID- 25574583
TI  - Synthesis and immunestimulating activity of lactobacilli-originated
      polysaccharide-polymeric microparticle conjugates.
AB  - The design and synthesis of biomaterials capable of activating the immune system
      are of interest in immunology-related fields because of their ability to tune up
      the immune defenses of the host. Lactobacilli are a major constituent of normal
      human indigenous flora, and some specific strains are known to activate the
      immune system of the host as probiotics. In this study, we first fabricated novel
      biohybrid materials in which lactobacilli (L. casei strain Shirota, LcS)
      originated polysaccharide-peptidoglycan complexes (PS-PGs) are conjugated with
      polymeric microparticles (MPs). PS-PGs conjugated onto polymeric MPs surfaces
      bound its specific antibody, suggesting that PS-PGs kept their original molecular
      recognition ability. The PS-PGs-based hybrid MPs with an appropriate density of
      conjugated PS-PGs effectively induced high levels of IL-12 production from
      macrophages without cytotoxicity. These results suggest that LcS-originated PS
      PGs could be available bio-originated materials for developing novel biomaterials
      capable of activating the immune system in a safe manner. 

PMID- 25574584
TI  - Controlling mesopore size and processability of transparent enzyme-loaded silica
      films for biosensing applications.
AB  - Silica-based nanoporous thin films including large mesopores are relevant as
      enzyme supports for applications in biosensing. The diffusion and immobilization
      of large biomolecules such as enzymes in such porous films require the presence
      of large mesopores. Creating such morphologies based on a bottom-up synthesis
      using colloidal templates is a challenge in view of the combination of desired
      material properties and the robustness of the casting process for the fabrication
      of thin films. Here a strategy to reproducibly synthesize transparent porous
      silica thin films with submicrometer thickness and homogeneously distributed
      porosity is presented. For this purpose, polystyrene-poly-2-vinylpyridine (PS
      P2VP) amphiphilic block copolymers are used as porogenic templates. Low-chain
      alcohols are employed as both selective solvents for the P2VP blocks and reaction
      media for silica synthesis. Rheology measurements reveal a strong influence of
      the block copolymer length on the behavior of PS-P2VP micelles in suspension. The
      pore distribution and accessibility into the film are controlled by adjusting the
      silica to block copolymer weight ratio. The solvent choice is shown to control
      not only the micelle size and the generated pore morphology but also the
      structural homogeneity of the films. Finally, the suitability of the synthesized
      films as supports for enzymes is tested using a model enzyme, horseradish
      peroxidase EC 1.11.1.7. Our approach is innovative, robust, and reproducible and
      provides a convenient alternative to synthesize large mesopores up to small
      macropores (20-100 nm) in nanostructured thin films with applications in
      biosensing and functional coatings. 

PMID- 25574585
TI  - Acid-fast Smear and Histopathology Results Provide Guidance for the Appropriate
      Use of Broad-Range Polymerase Chain Reaction and Sequencing for Mycobacteria.
AB  - CONTEXT: New molecular diagnostic tests are attractive because of the potential
      they hold for improving diagnostics in microbiology. The value of these tests,
      which is often assumed, should be investigated to determine the best use of these
      potentially powerful tools. OBJECTIVE: To investigate the usefulness of broad
      range polymerase chain reaction (PCR), followed by sequencing, in mycobacterial
      infections. DESIGN: We reviewed the test performance of acid-fast bacilli (AFB)
      PCR and traditional diagnostic methods (histopathology, AFB smear, and culture).
      We assessed the diagnostic effect and cost of the unrestricted ordering of broad
      range PCR for the detection and identification of mycobacteria in clinical
      specimens. RESULTS: The AFB PCR was less sensitive than culture and
      histopathology and was less specific than culture, AFB smear, and histopathology.
      During 18 months, $93 063 was spent on 183 patient specimens for broad-range PCR
      and DNA sequencing for mycobacteria to confirm one culture-proven Mycobacterium
      tuberculosis infection that was also known to be positive by AFB smear and
      histopathology. In this cohort, there was a false-negative AFB PCR for M
      tuberculosis and a false-positive AFB PCR for Mycobacterium lentiflavum .
      CONCLUSION: Testing of AFB smear-negative specimens from patients without an
      inflammatory response supportive of a mycobacterial infection is costly and has
      not been proven to improve patient care. Traditional diagnostics (histopathology,
      AFB smear, and culture) should remain the primary methods for the detection of
      mycobacteria in clinical specimens.

PMID- 25574586
TI  - Effects of high-dose microbeam irradiation on tumor microvascular function and
      angiogenesis.
AB  - Microbeam radiation therapy (MRT) is a form of cancer treatment in which a single
      large dose of radiation is spatially fractionated in-line or grid-like patterns.
      Preclinical studies have demonstrated that MRT is capable of eliciting high
      levels of tumor response while sparing normal tissue that is exposed to the same
      radiation field. Since a large fraction of the MRT-treated tumor is in the dose
      valley region that is not directly irradiated, tumor response may be driven by
      radiation bystander effects, which in turn elicit a microvascular response.
      Differential alterations in hemodynamics between the tumor and normal tissue may
      explain the therapeutic advantages of MRT. Direct observation of these dynamic
      responses presents a challenge for conventional ex vivo analysis. Furthermore,
      knowledge gleaned from in vitro studies of radiation bystander response has not
      been widely incorporated into in vivo models of tumor radiotherapy, and the
      biological contribution of the bystander effect within the tumor microenvironment
      is unknown. In this study, we employed noninvasive, serial observations of the
      tumor microenvironment to address the question of how tumor vasculature and HIF-1
      expression are affected by microbeam radiotherapy. Tumors (approximately 4 mm in
      diameter) grown in a dorsal window chamber were irradiated in a single fraction
      using either a single, microplanar beam (300 micron wide swath) or a wide-field
      setup (whole-window chamber) to a total dose of 50 Gy. The tumors were optically
      observed daily for seven days postirradiation. Microvascular changes in the tumor
      and surrounding normal tissue differed greatly between the wide-field and
      microbeam treatments. We present evidence that these changes may be due to
      dissimilar spatial and temporal patterns of HIF-1 expression induced through
      radiation bystander effects. 

PMID- 25574587
TI  - Accounting for shared and unshared dosimetric uncertainties in the dose response
      for ultrasound-detected thyroid nodules after exposure to radioactive fallout.
AB  - Dosimetic uncertainties, particularly those that are shared among subgroups of a
      study population, can bias, distort or reduce the slope or significance of a dose
      response. Exposure estimates in studies of health risks from environmental
      radiation exposures are generally highly uncertain and thus, susceptible to these
      methodological limitations. An analysis was published in 2008 concerning
      radiation-related thyroid nodule prevalence in a study population of 2,994
      villagers under the age of 21 years old between August 1949 and September 1962
      and who lived downwind from the Semipalatinsk Nuclear Test Site in Kazakhstan.
      This dose-response analysis identified a statistically significant association
      between thyroid nodule prevalence and reconstructed doses of fallout-related
      internal and external radiation to the thyroid gland; however, the effects of
      dosimetric uncertainty were not evaluated since the doses were simple point "best
      estimates". In this work, we revised the 2008 study by a comprehensive treatment
      of dosimetric uncertainties. Our present analysis improves upon the previous
      study, specifically by accounting for shared and unshared uncertainties in dose
      estimation and risk analysis, and differs from the 2008 analysis in the following
      ways: 1. The study population size was reduced from 2,994 to 2,376 subjects,
      removing 618 persons with uncertain residence histories; 2. Simulation of
      multiple population dose sets (vectors) was performed using a two-dimensional
      Monte Carlo dose estimation method; and 3. A Bayesian model averaging approach
      was employed for evaluating the dose response, explicitly accounting for large
      and complex uncertainty in dose estimation. The results were compared against
      conventional regression techniques. The Bayesian approach utilizes 5,000
      independent realizations of population dose vectors, each of which corresponds to
      a set of conditional individual median internal and external doses for the 2,376
      subjects. These 5,000 population dose vectors reflect uncertainties in dosimetric
      parameters, partly shared and partly independent, among individual members of the
      study population. Risk estimates for thyroid nodules from internal irradiation
      were higher than those published in 2008, which results, to the best of our
      knowledge, from explicitly accounting for dose uncertainty. In contrast to
      earlier findings, the use of Bayesian methods led to the conclusion that the
      biological effectiveness for internal and external dose was similar. Estimates of
      excess relative risk per unit dose (ERR/Gy) for males (177 thyroid nodule cases)
      were almost 30 times those for females (571 cases) and were similar to those
      reported for thyroid cancers related to childhood exposures to external and
      internal sources in other studies. For confirmed cases of papillary thyroid
      cancers (3 in males, 18 in females), the ERR/Gy was also comparable to risk
      estimates from other studies, but not significantly different from zero. These
      findings represent the first reported dose response for a radiation epidemiologic
      study considering all known sources of shared and unshared errors in dose
      estimation and using a Bayesian model averaging (BMA) method for analysis of the
      dose response. 

PMID- 25574589
TI  - tRNA binding with anti-cancer alkaloids-nature of interaction and comparison with
      DNA-alkaloids adducts.
AB  - Vincristine and vinblastine are potent anti-proliferative compound whose
      mechanism of action inside a cell is not well elucidated and the basis of their
      differential cellular effect is also unknown. This work focuses towards
      understanding the interaction of vincristine and vinblastine with tRNA using
      spectroscopic approach. Fourier transform infrared (FTIR) spectroscopy, Fourier
      transform infrared difference spectroscopy and UV-visible spectroscopy were used
      to study the binding parameters of tRNA-alkaloids interaction. Both the vinca
      alkaloids interact with tRNA through external binding with some degree of
      intercalation into the nitrogenous bases. The alkaloids adduct formation did not
      alter the A-conformation of the biopolymer and vincristine-tRNA complexes were
      found to be more stable than that of vinblastine-tRNA complexes. The binding
      constants (K) estimated for VCR-tRNA and VBS-tRNA complexation are 3*10(2)M(-1)
      and 2.5*10(2)M(-1) respectively, which suggests low affinity of alkaloids to
      tRNA. The study recognizes tRNA binding properties of vital vinca alkaloids and
      contributes to a better understanding of their mechanism of action and could also
      help in identifying the reason behind their diverse action in a cell. 

PMID- 25574588
TI  - PicoGreen assay of circular DNA for radiation biodosimetry.
AB  - We developed a simple, rapid and quantitative assay using the fluorescent probe
      PicoGreen to measure the concentration of ionizing radiation-induced double
      stranded DNA (dsDNA) in mouse plasma, and we correlated this concentration with
      the radiation dose. With 70 MUl of blood obtained by fingerstick, this 30 min
      assay reduces protein interference without extending sample processing time.
      Plasma from nonirradiated mice (BALB/c and NIH Swiss) was pooled, diluted and
      spiked with dsDNA to establish sensitivity and reproducibility of the assay to
      quantify plasma dsDNA. The assay was then used to directly quantify dsDNA in
      plasma at 0-48 h after mice received 0-10 Gy total-body irradiation (TBI). There
      are three optimal conditions for this assay: 1:10 dilution of plasma in water;
      1:200 dilution of PicoGreen reagent in water; and calibration of radiation
      induced dsDNA concentration through a standard addition method using serial
      spiking of samples with genomic dsDNA. Using the internal standard calibration
      curve of the spiked samples method, the signal developed within 5 min, exhibiting
      a linear signal (r(2) = 0.997). The radiation-induced elevation of plasma DNA in
      mice started at 1-3 h, peaked at 9 h and gradually returned to baseline at 24 h
      after TBI (6 Gy). DNA levels in plasma collected from mice 9 h after 0-10 Gy TBI
      correlated strongly with dose (r(2) = 0.991 and 0.947 for BALB/c and NIH Swiss,
      respectively). Using the PicoGreen assay, we observed a radiation dose-dependent
      response in extracellular plasma DNA 9 h after irradiation with an assay time <=
      30 min.

PMID- 25574592
TI  - Solvent-free synthesis of zeolites from anhydrous starting raw solids.
AB  - Development of sustainable routes for synthesis of zeolites is very important
      because of wide applications of zeolites at large scale in the fields of
      catalysis, adsorption, and separation. Here we report a novel and generalized
      route for synthesis of zeolites in the presence of NH4F from grinding the
      anhydrous starting solid materials and heating at 140-240  degrees C.
      Accordingly, zeolites of MFI, BEA*, EUO, and TON structures have been
      successfully synthesized. The presence of F(-) drives the crystallization of
      these zeolites from amorphous phase. Compared with conventional hydrothermal
      synthesis, the synthesis in this work not only simplifies the synthesis process
      but also significantly enhances the zeolite yields. These features should be
      potentially of great importance for industrial production of zeolites at large
      scale in the future. 

PMID- 25574590
TI  - Solvent-Induced Changes in Photophysics and Photostability of Indole
      Naphthyridines.
AB  - Molecules that can simultaneously act as hydrogen bond donors and acceptors often
      exhibit completely different photophysical behavior in protic and aprotic
      solvents. Formation of multiple hydrogen bonds with, for example, water or
      alcohols, may lead to enhanced internal conversion; as a result, triplet
      formation efficiency can be reduced. These changes in photophysical
      characteristics may influence the photostability. In order to check this
      hypothesis, we have investigated spectroscopy, photophysics, and changes in
      photostability caused by interaction with aprotic and protic solvents for 2-(1'H
      indol-2'-yl)-[1,5]naphthyridine and 2-(1'H-indol-2'-yl)-[1,8]naphthyridine,
      molecules with hydrogen bond accepting and donating functionalities. The
      photostability of these compounds in n-hexane, acetonitrile, and alcohols was
      studied in the regime of 365 nm irradiation. The photodegradation yield was found
      to be significantly lower in alcohols. In polar and protic solvents, the presence
      of two species was detected and attributed to syn and anti rotameric forms; the
      former are dominant in all environments. 

PMID- 25574594
TI  - Correction.

PMID- 25574593
TI  - Relationship between beta-cell function, metabolic control, and microvascular
      complications in type 2 diabetes mellitus.
AB  - BACKGROUND: This study investigated the relationship among beta-cell function,
      metabolic control, and diabetic microvascular complications in patients with type
      2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: In total, 885 patients with
      type 2 diabetes mellitus (DM) were recruited from January 2012 to January 2014
      and grouped into three groups according to the area under the curve of C-peptide
      [AUC(C-pep)] during the 75-g oral glucose tolerance test. Logistic regression
      analyses were used to evaluate the association between C-peptide and
      microvascular complications. RESULTS: The prevalence of diabetic microvascular
      complications decreased from the first to the third AUC(C-pep) tertile (P < 0.01
      for all), whereas the rates of nonalcoholic fatty liver disease (NAFLD) was
      positively associated with AUC(C-pep) values. Patients with lower AUC(C-pep)
      tertile exhibited higher levels of glycosylated hemoglobin and high-density
      lipoprotein cholesterol and longer duration of DM; however, levels of
      triglycerides, fasting C-peptide, 2-h C-peptide, body mass index, and homeostasis
      model assessment of insulin resistance index were lower compared with the third
      tertile. Comparison among patients with a similar DM duration showed a higher
      level of AUC(C-pep) was inversely associated with prevalence of microvascular
      complications. The odds ratios for nephropathy, retinopathy, and neuropathy in
      the lowest versus the highest AUC(C-pep) tertile were 3.10 (95% confidence
      interval, 2.01-4.78), 2.83 (1.73-4.64), and 2.04 (1.37-3.04) after adjustment for
      confounding factors. CONCLUSIONS: Higher AUC(C-pep) levels were associated with a
      decreased prevalence of microvascular complications and a good level of glycemic
      control, whereas higher endogenous insulin levels were linked to the components
      of metabolic syndrome and increased rates of NAFLD.

PMID- 25574595
TI  - Noise reduction of nuclear magnetic resonance (NMR) transversal data using
      improved wavelet transform and exponentially weighted moving average (EWMA).
AB  - NMR logging and core NMR signals acts as an effective way of pore structure
      evaluation and fluid discrimination, but it is greatly contaminated by noise for
      samples with low magnetic resonance intensity. Transversal relaxation time (T(2))
      spectrum obtained by inversion of decay signals intrigued by Carr-Purcell-Meiboom
      Gill (CPMG) sequence may deviate from the truth if the signal-to-noise ratio
      (SNR) is imperfect. A method of combing the improved wavelet thresholding with
      the EWMA is proposed for noise reduction of decay data. The wavelet basis
      function and decomposition level are optimized in consideration of information
      entropy and white noise estimation firstly. Then a hybrid threshold function is
      developed to avoid drawbacks of hard and soft threshold functions. To achieve the
      best thresholding values of different levels, a nonlinear objective function
      based on SNR and mean square error (MSE) is constructed, transforming the problem
      to a task of finding optimal solutions. Particle swarm optimization (PSO) is used
      to ensure the stability and global convergence. EWMA is carried out to eliminate
      unwanted peaks and sawtooths of the wavelet denoised signal. With validations of
      numerical simulations and experiments, it is demonstrated that the proposed
      approach can reduce the noise of T(2) decay data perfectly.

PMID- 25574596
TI  - A supramolecular keypad lock.
AB  - The reversible photoswitching between an anthracene derivative and its [4+4]
      dimer, using the template effect of the CB8 macrocycle, was demonstrated. This
      example of supramolecular chemistry in water was harnessed to demonstrate the
      operation of a keypad lock device that is driven by means of light and chemicals
      as inputs. 

PMID- 25574597
TI  - Cue-induced activation of implicit affective associations with heroin use in
      abstinent heroin abusers.
AB  - BACKGROUND AND OBJECTIVES: While drug-related contexts have been shown to
      influence drug users' implicit and explicit drug-related cognitions, this has
      been minimally explored in heroin abusers. This study examined the effect of
      heroin-related cue exposure on implicit and explicit valence and arousal-sedation
      associations with heroin use for abstinent heroin abusers. METHODS: In Experiment
      1, 39 male abstinent heroin abusers were exposed to heroin-related words and
      reported cravings before and after cue exposure. They subsequently performed two
      Extrinsic Affective Simon Tasks (EASTs), which were used to assess implicit
      valence and arousal-sedation associations with heroin use. Thirty-six male
      abstinent heroin abusers (controls) only performed the two EASTs. All
      participants completed measures of explicit expectancy regarding heroin use. In
      Experiment 2, twenty-eight newly recruited abstinent heroin abusers were exposed
      to heroin-related pictures, and completed the same implicit and explicit measures
      used in Experiment 1. RESULTS: A non-significant increase in craving after cue
      exposure was observed. While participants exposed to heroin-related words or
      pictures exhibited more positive implicit heroin use associations (relative to
      negative associations), and such trend was not observed in controls, this
      difference was not significant across groups. Participants still indicated
      negative explicit associations with heroin use after cue exposure. Exposure to
      cues significantly accelerated arousal and sedation responses. LIMITATIONS:
      Whether cue exposure could change self-reported craving requires further study in
      abstinent heroin abusers. The exclusively male sample limits generalization of
      the results. CONCLUSIONS: The present findings extend the evidence on whether
      implicit and explicit heroin-related cognitions are susceptible to context.

PMID- 25574599
TI  - Origin of ion selectivity at the air/water interface.
AB  - Among many characteristics of ions, their capability to accumulate at air/water
      interfaces is a particular issue that has been the subject of much research
      attention. For example, the accumulation of halide anions (Cl(-), Br(-), I(-)) at
      the water surface is of great importance to heterogeneous reactions that are of
      environmental concern. However, the actual mechanism that drives anions towards
      the air/water interface remains unclear. In this work, we have performed
      atomistic simulations using polarizable models to mimic ionic behavior under
      atmospheric conditions. We find that larger anions are abundant at the water
      surface and that the cations are pulled closer to the surface by the counterions.
      We propose that polarization effects stabilize the anions with large radii when
      approaching the surface. This energetically more favorable situation is caused by
      the fact that the more polarized anions at the surface attract water molecules
      more strongly. Of relevance is also the ordering of the surface water molecules
      with their hydrogen atoms pointing outwards which induce an external electronic
      field that leads to a different surface behavior of anions and cations. The water
      water interaction is weakened by the distinct water-ion attraction, a point
      contradicting the proposition that F(-) is a kosmotrope. The simulation results
      thus allow us to obtain a more holistic understanding of the interfacial
      properties of ionic solutions and atmospheric aerosols. 

PMID- 25574598
TI  - BCL11A is a triple-negative breast cancer gene with critical functions in stem
      and progenitor cells.
AB  - Triple-negative breast cancer (TNBC) has poor prognostic outcome compared with
      other types of breast cancer. The molecular and cellular mechanisms underlying
      TNBC pathology are not fully understood. Here, we report that the transcription
      factor BCL11A is overexpressed in TNBC including basal-like breast cancer (BLBC)
      and that its genomic locus is amplified in up to 38% of BLBC tumours. Exogenous
      BCL11A overexpression promotes tumour formation, whereas its knockdown in TNBC
      cell lines suppresses their tumourigenic potential in xenograft models. In the
      DMBA-induced tumour model, Bcl11a deletion substantially decreases tumour
      formation, even in p53-null cells and inactivation of Bcl11a in established
      tumours causes their regression. At the cellular level, Bcl11a deletion causes a
      reduction in the number of mammary epithelial stem and progenitor cells. Thus,
      BCL11A has an important role in TNBC and normal mammary epithelial cells. This
      study highlights the importance of further investigation of BCL11A in TNBC
      targeted therapies. 

PMID- 25574600
TI  - E2F1-mediated FOS induction in arsenic trioxide-induced cellular transformation:
      effects of global H3K9 hypoacetylation and promoter-specific hyperacetylation in
      vitro.
AB  - BACKGROUND: Aberrant histone acetylation has been observed in carcinogenesis and
      cellular transformation associated with arsenic exposure; however, the molecular
      mechanisms and cellular outcomes of such changes are poorly understood.
      OBJECTIVE: We investigated the impact of tolerated and toxic arsenic trioxide
      (As2O3) exposure in human embryonic kidney (HEK293T) and urothelial (UROtsa)
      cells to characterize the alterations in histone acetylation and gene expression
      as well as the implications for cellular transformation. METHODS: Tolerated and
      toxic exposures of As2O3 were identified by measurement of cell death,
      mitochondrial function, cellular proliferation, and anchorage-independent growth.
      Histone extraction, the MNase sensitivity assay, and immunoblotting were used to
      assess global histone acetylation levels, and gene promoter-specific interactions
      were measured by chromatin immunoprecipitation followed by reverse-transcriptase
      polymerase chain reaction. RESULTS: Tolerated and toxic dosages, respectively,
      were defined as 0.5 MUM and 2.5 MUM As2O3 in HEK293T cells and 1 MUM and 5 MUM
      As2O3 in UROtsa cells. Global hypoacetylation of H3K9 at 72 hr was observed in
      UROtsa cells following tolerated and toxic exposure. In both cell lines,
      tolerated exposure alone led to H3K9 hyperacetylation and E2F1 binding at the FOS
      promoter, which remained elevated after 72 hr, contrary to global H3K9
      hypoacetylation. Thus, promoter-specific H3K9 acetylation is a better predictor
      of cellular transformation than are global histone acetylation patterns.
      Tolerated exposure resulted in an increased expression of the proto-oncogenes FOS
      and JUN in both cell lines at 72 hr. CONCLUSION: Global H3K9 hypoacetylation and
      promoter-specific hyperacetylation facilitate E2F1-mediated FOS induction in
      As2O3-induced cellular transformation.

PMID- 25574602
TI  - The oxidative fermentation of ethanol in Gluconacetobacter diazotrophicus is a
      two-step pathway catalyzed by a single enzyme: alcohol-aldehyde Dehydrogenase
      (ADHa).
AB  - Gluconacetobacter diazotrophicus is a N2-fixing bacterium endophyte from sugar
      cane. The oxidation of ethanol to acetic acid of this organism takes place in the
      periplasmic space, and this reaction is catalyzed by two membrane-bound enzymes
      complexes: the alcohol dehydrogenase (ADH) and the aldehyde dehydrogenase (ALDH).
      We present strong evidence showing that the well-known membrane-bound Alcohol
      dehydrogenase (ADHa) of Ga. diazotrophicus is indeed a double function enzyme,
      which is able to use primary alcohols (C2-C6) and its respective aldehydes as
      alternate substrates. Moreover, the enzyme utilizes ethanol as a substrate in a
      reaction mechanism where this is subjected to a two-step oxidation process to
      produce acetic acid without releasing the acetaldehyde intermediary to the media.
      Moreover, we propose a mechanism that, under physiological conditions, might
      permit a massive conversion of ethanol to acetic acid, as usually occurs in the
      acetic acid bacteria, but without the transient accumulation of the highly toxic
      acetaldehyde. 

PMID- 25574601
TI  - Molecular targeting of the oncoprotein PLK1 in pediatric acute myeloid leukemia:
      RO3280, a novel PLK1 inhibitor, induces apoptosis in leukemia cells.
AB  - Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a
      biomarker of transformation and potential target for the development of cancer
      specific small molecule drugs. RO3280 was recently identified as a novel PLK1
      inhibitor; however its therapeutic effects in leukemia treatment are still
      unknown. We found that the PLK1 protein was highly expressed in leukemia cell
      lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples.
      PLK1 mRNA expression was significantly higher in AML samples compared with
      control samples (82.95 +/- 110.28 vs. 6.36 +/- 6.35; p < 0.001). Kaplan-Meier
      survival analysis revealed that shorter survival time correlated with high tumor
      PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280
      for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary
      acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM
      and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle
      disorder in leukemia cells. RO3280 treatment regulated several apoptosis
      associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by
      western blot. These results provide insights into the potential use of RO3280 for
      AML therapy; however, the underlying mechanisms remain to be determined. 

PMID- 25574605
TI  - Age and gender specific biokinetic model for strontium in humans.
AB  - A biokinetic model for strontium in humans is necessary for quantification of
      internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic
      model for strontium has limitations for use in a population study, because it is
      not gender specific and does not cover all age ranges. The extensive Techa River
      data set on (90)Sr in humans (tens of thousands of measurements) is a unique
      source of data on long-term strontium retention for men and women of all ages at
      intake. These, as well as published data, were used for evaluation of age- and
      gender-specific parameters for a new compartment biokinetic model for strontium
      (Sr-AGe model). The Sr-AGe model has a similar structure to the ICRP model for
      the alkaline earth elements. The following parameters were mainly re-evaluated:
      gastrointestinal absorption and parameters related to the processes of bone
      formation and resorption defining calcium and strontium transfers in skeletal
      compartments. The Sr-AGe model satisfactorily describes available data sets on
      strontium retention for different kinds of intake (dietary and intravenous) at
      different ages (0-80 years old) and demonstrates good agreement with data sets
      for different ethnic groups. The Sr-AGe model can be used for dose assessment in
      epidemiological studies of general populations exposed to ingested strontium
      radioisotopes.

PMID- 25574604
TI  - No association between HMOX1 and risk of colorectal cancer and no interaction
      with diet and lifestyle factors in a prospective Danish case-cohort study.
AB  - Red meat is a risk factor for colorectal cancer (CRC). We wanted to evaluate
      whether a functional polymorphism in the HMOX1 gene encoding heme oxygenase
      modifies risk of CRC or interacts with diet or lifestyle factors because this
      would identify heme or heme iron as a risk factor of CRC. The HMOX1 A-413T
      (rs2071746) was assessed in relation to risk of colorectal cancer (CRC) and
      interactions with diet (red meat, fish, fiber, cereals, fruit and vegetables) and
      lifestyle (use of non-steroidal anti-inflammatory drug and smoking status) were
      assessed in a case-cohort study of 928 CRC cases and a comparison group of 1726
      randomly selected participants from a prospective study of 57,053 persons. No
      association between HMOX1 A-413T and CRC risk was found (TT vs. AA + TA; IRR =
      1.15, 95% CI: 0.98-1.36, p = 0.10 for the adjusted estimate). No interactions
      were found between diet or lifestyle and HMOX1 A-413T. HMOX1 A-413T was not
      associated with CRC risk and no interactions with diet or lifestyle were
      identified in this large, prospective cohort with high meat intake. The results
      reproduced the previous findings from the same cohort and did not support a link
      between heme or heme iron and colorectal cancer. These results should be sought
      and replicated in other well-characterized cohorts with high meat intake. 

PMID- 25574606
TI  - Cost-effective sampling of 137Cs-derived net soil redistribution: part 1-
      estimating the spatial mean across scales of variation.
AB  - The (137)Cs technique for estimating net time-integrated soil redistribution is
      valuable for understanding the factors controlling soil redistribution by all
      processes. The literature on this technique is dominated by studies of individual
      fields and describes its typically time-consuming nature. We contend that the
      community making these studies has inappropriately assumed that many (137)Cs
      measurements are required and hence estimates of net soil redistribution can only
      be made at the field scale. Here, we support future studies of (137)Cs-derived
      net soil redistribution to apply their often limited resources across scales of
      variation (field, catchment, region etc.) without compromising the quality of the
      estimates at any scale. We describe a hybrid, design-based and model-based,
      stratified random sampling design with composites to estimate the sampling
      variance and a cost model for fieldwork and laboratory measurements.
      Geostatistical mapping of net (1954-2012) soil redistribution as a case study on
      the Chinese Loess Plateau is compared with estimates for several other sampling
      designs popular in the literature. We demonstrate the cost-effectiveness of the
      hybrid design for spatial estimation of net soil redistribution. To demonstrate
      the limitations of current sampling approaches to cut across scales of variation,
      we extrapolate our estimate of net soil redistribution across the region, show
      that for the same resources, estimates from many fields could have been provided
      and would elucidate the cause of differences within and between regional
      estimates. We recommend that future studies evaluate carefully the sampling
      design to consider the opportunity to investigate (137)Cs-derived net soil
      redistribution across scales of variation. 

PMID- 25574603
TI  - Whole exome sequencing in females with autism implicates novel and candidate
      genes.
AB  - Classical autism or autistic disorder belongs to a group of genetically
      heterogeneous conditions known as Autism Spectrum Disorders (ASD). Heritability
      is estimated as high as 90% for ASD with a recently reported compilation of 629
      clinically relevant candidate and known genes. We chose to undertake a
      descriptive next generation whole exome sequencing case study of 30 well
      characterized Caucasian females with autism (average age, 7.7 +/- 2.6 years; age
      range, 5 to 16 years) from multiplex families. Genomic DNA was used for whole
      exome sequencing via paired-end next generation sequencing approach and X
      chromosome inactivation status. The list of putative disease causing genes was
      developed from primary selection criteria using machine learning-derived
      classification score and other predictive parameters (GERP2, PolyPhen2, and
      SIFT). We narrowed the variant list to 10 to 20 genes and screened for biological
      significance including neural development, function and known neurological
      disorders. Seventy-eight genes identified met selection criteria ranging from 1
      to 9 filtered variants per female. Five females presented with functional
      variants of X-linked genes (IL1RAPL1, PIR, GABRQ, GPRASP2, SYTL4) with cadherin,
      protocadherin and ankyrin repeat gene families most commonly altered (e.g., CDH6,
      FAT2, PCDH8, CTNNA3, ANKRD11). Other genes related to neurogenesis and neuronal
      migration (e.g., SEMA3F, MIDN), were also identified. 

PMID- 25574607
TI  - Plutonium sorption and desorption behavior on bentonite.
AB  - Understanding plutonium (Pu) sorption to, and desorption from, mineral phases is
      key to understanding its subsurface transport. In this work we study Pu(IV)
      sorption to industrial grade FEBEX bentonite over the concentration range 10(-7)
      10(-16) M to determine if sorption at typical environmental concentrations (<=10(
      12) M) is the same as sorption at Pu concentrations used in most laboratory
      experiments (10(-7)-10(-11) M). Pu(IV) sorption was broadly linear over the 10(
      7)-10(-16) M concentration range during the 120 d experimental period; however,
      it took up to 100 d to reach sorption equilibrium. At concentrations >=10(-8) M,
      sorption was likely affected by additional Pu(IV) precipitation/polymerization
      reactions. The extent of sorption was similar to that previously reported for
      Pu(IV) sorption to SWy-1 Na-montmorillonite over a narrower range of Pu
      concentrations (10(-11)-10(-7) M). Sorption experiments with FEBEX bentonite and
      Pu(V) were also performed across a concentration range of 10(-11)-10(-7) M and
      over a 10 month period which allowed us to estimate the slow apparent rates of
      Pu(V) reduction on a smectite-rich clay. Finally, a flow cell experiment with
      Pu(IV) loaded on FEBEX bentonite demonstrated continued desorption of Pu over a
      12 day flow period. Comparison with a desorption experiment performed with SWy-1
      montmorillonite showed a strong similarity and suggested the importance of
      montorillonite phases in controlling Pu sorption/desorption reactions on FEBEX
      bentonite.

PMID- 25574609
TI  - Relative Importance of Four Muscle Groups for Indoor Rock Climbing Performance.
AB  - Little research is available to guide training programs for rock climbers. To
      help meet this need, we sought to determine the relative importance of 4 muscle
      groups for rock climbing performance. Eleven male climbers were familiarized with
      an indoor climbing route before 5 separate days of testing. On testing days,
      subjects were randomly assigned to climb with no prefatiguing exercise (control
      climb) or after a prefatiguing exercise designed to specifically target the digit
      flexors (DF), shoulder adductors (SA), elbow flexors (EF), or lumbar flexors
      (LF). Immediately after the prefatiguing exercise, the subject climbed the route
      as far as possible without rest until failure. The number of climbing moves was
      recorded for each climb. Surface electromyography of the target muscles was
      recorded during the prefatigue. Fewer climbing moves were completed after
      prefatigue of the DF (50 +/- 18%) and EF (78 +/- 22%) (p <= 0.05) compared with
      the control climb. The number of moves completed after prefatigue of the LF and
      SA were not statistically significant compared with the control climb (p > 0.05).
      The short time lapse between the end of prefatiguing exercise and the start of
      climbing (transit time), which may have allowed for some recovery, was not
      different among trials (p > 0.05). Electromyography median frequency was reduced
      from beginning to end of each prefatiguing exercise. These results suggest that
      among the muscle groups studied in men, muscular endurance of DF and EF muscle
      groups is especially important for rock climbing on 40 degrees  overhanging
      terrain.

PMID- 25574608
TI  - Numerical simulation of the transport of a radionuclide chain in a rock medium.
AB  - For the safe disposal of High Level Waste (HLW), a common practice is to bury the
      sealed container called canister containing the concentrated and vitrified waste
      deep inside the earth surface within a rocky medium. In the event of an
      accidental breach of such a canister, the sealed waste may come in contact of
      pore water. If this happens, then the parent nuclides present in the HLW and
      their daughters generated by the radioactive decay reaction start migrating
      through the surrounding rock medium due to the combined effect of advection and
      diffusion. The accurate estimation of the transport of such a chain through a
      rock is important for radiological safety. Here, we report a finite difference
      based numerical simulation to address the issue. To simplify the problem, we
      consider the rock to be a collection of identical parallel fractures separated by
      porous matrices of equal width with a source at one end. A Forward Time and
      Centered Space (FTCS) finite difference scheme is implemented to solve the set of
      coupled partial differential equations that govern the transport mechanism. The
      scheme is validated using the methods available in the literature and
      subsequently it is applied to estimate the time dependent buildup of the active
      elements of a chain. Two independent chains each with three members are
      considered for simulation to address the safety related issues. 

PMID- 25574610
TI  - Efficacy of the National Football League-225 Test to Track Changes in One
      Repetition Maximum Bench Press After Training in National Collegiate Athletic
      Association Division IA Football Players.
AB  - Numerous investigations have attested to the efficacy of the National Football
      League (NFL)-225 test to estimate one repetition maximum (1RM) bench press.
      However, no studies have assessed the efficacy of the test to track changes in
      strength across a training program. The purpose of this study was to determine
      the accuracy of the NFL-225 test for determining the change in 1RM bench press in
      National Collegiate Athletic Association Division IA college football players
      after training. Over a 4-year period, players (n = 203) were assessed before and
      after a 6-week off-season resistance program for 1RM bench press and repetitions
      completed with 102.3 kg (225 lbs). Test sessions typically occurred within 1 week
      of each other. Players significantly increased 1RM by 4.2 +/- 8.6 kg and NFL-225
      repetitions by 0.9 +/- 2.3, although the effect size (ES) for each was trivial
      (ES = 0.03 and 0.07, respectively). National Football League 225 prediction
      equations had higher correlations with 1RM before training (intraclass
      correlation coefficient [ICC] = 0.95) than after training (ICC = 0.75). The
      correlation between the change in NFL-225 repetitions and change in 1RM was low
      and negative (r = -0.22, p < 0.02). Short-term heavy resistance training may
      alter the association between muscular strength and muscular endurance in college
      football players and render the NFL-225 test less effective in predicting the
      change in 1RM bench press strength after short-term training.

PMID- 25574611
TI  - Bring out your dead.

PMID- 25574612
TI  - IL-17-targeting biologics aim to become standard of care in psoriasis.

PMID- 25574615
TI  - Amgen's angiopoietin blocker fails in ovarian cancer.

PMID- 25574616
TI  - Clinuvel's tanning agent nears approval for porphyria.

PMID- 25574617
TI  - Foundation receives $3.3-billion windfall for Kalydeco.

PMID- 25574621
TI  - IBM's Watson Group signs up genomics partners.

PMID- 25574622
TI  - How frothy is this IPO window?

PMID- 25574623
TI  - USDA approves next-generation GM potato.

PMID- 25574625
TI  - Social storm.

PMID- 25574627
TI  - Biosimilars or semi-similars?

PMID- 25574628
TI  - Outcubation--where incubation meets outsourcing.

PMID- 25574629
TI  - PeptideShaker enables reanalysis of MS-derived proteomics data sets.

PMID- 25574630
TI  - Intellectual property issues and synthetic biology standards.

PMID- 25574631
TI  - Status and market potential of transgenic biofortified crops.

PMID- 25574632
TI  - Reply to Intellectual property issues and synthetic biology standards.

PMID- 25574633
TI  - Selling long life.

PMID- 25574634
TI  - The impact of European embryonic stem cell patent decisions on research
      strategies.

PMID- 25574635
TI  - Cancer immunotherapy meets biomaterials.

PMID- 25574636
TI  - Modeling the course of amyotrophic lateral sclerosis.

PMID- 25574637
TI  - Systematic discovery of probiotics.

PMID- 25574639
TI  - DREAMing of benchmarks.

PMID- 25574640
TI  - Life sciences workforce trends evolve with the industry.

PMID- 25574642
TI  - Really exasperating viral protein from HIV.
AB  - Two new structures shed additional light on the nuclear transport of viral
      transcripts. 

PMID- 25574643
TI  - Treatment of proximal humerus fractures in the elderly: a systemic review of 409
      patients.
AB  - BACKGROUND AND PURPOSE: There is no consensus on the treatment of proximal
      humerus fractures in the elderly. PATIENTS AND METHODS: We conducted a systematic
      search of the medical literature for randomized controlled trials and controlled
      clinical trials from 1946 to Apr 30, 2014. Predefined PICOS criteria were used to
      search relevant publications. We included randomized controlled trials involving
      2- to 4-part proximal humerus fractures in patients over 60 years of age that
      compared operative treatment to any operative or nonoperative treatment, with a
      minimum of 20 patients in each group and a minimum follow-up of 1 year. Outcomes
      had to be assessed with functional or disability measures, or a quality-of-life
      score. RESULTS: After 2 independent researchers had read 777 abstracts, 9
      publications with 409 patients were accepted for the final analysis. No
      statistically significant differences were found between nonoperative treatment
      and operative treatment with a locking plate for any disability, for quality-of
      life score, or for pain, in patients with 3- or 4-part fractures. In 4-part
      fractures, 2 trials found similar shoulder function between hemiarthroplasty and
      nonoperative treatment. 1 trial found slightly better health-related quality of
      life (higher EQ-5D scores) at 2-year follow-up after hemiarthroplasty.
      Complications were common in the operative treatment groups (10-29%).
      INTERPRETATION: Nonoperative treatment over locking plate systems and tension
      banding is weakly supported. 2 trials provided weak to moderate evidence that for
      4-part fractures, shoulder function is not better with hemiarthroplasty than with
      nonoperative treatment. 1 of the trials provided limited evidence that health
      related quality of life may be better at 2-year follow-up after hemiarthroplasty.
      There is a high risk of complications after operative treatment.

PMID- 25574644
TI  - A novel fluorescent nano-chemosensor for cesium ions based on naphthalene
      macrocyclic derivative.
AB  - A new macrocyclic nano-chemosensor (L) was synthesized and characterized by
      common spectroscopic methods. Spectral properties of fluorescent macrocycle L
      were studied either as solution in ethanol or as insoluble nanoparticles in
      aqueous buffer solution. The nano-chemosensors with size about 40nm were prepared
      by nanoprecipitation method. The influence of metal cations such as Na(+), K(+),
      Cs(+), Mg(2+), Ba(2+), Al(3+), Pb(2+), Cr(3+), Mn(2+), Fe(3+), Fe(2+), Co(2+),
      Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Ag(+) on the spectroscopic properties
      of the chemosensor in aqueous buffer solution were investigated by means of
      emission spectrophotometry. The macrocycle was found to be as an effective
      fluorescence sensor for Cs(+) ions. 

PMID- 25574645
TI  - The advantage of spectrophotometric measurement for size-selective complexing of
      Cu(II) with O2N2-azacrown ligands.
AB  - A comparative investigation of the interaction of Cu(II) with a series of 15- to
      19-membered mixed-donor dibenzo-substituted macrocyclic ligands, each
      incorporating an O2N2-donor set, has been carried out using UV-Visible studies in
      methanol. Although a ring size effect has been reported for a related series of
      Ni(II) complexes, no such metal ion discrimination has been reported for Cu(II)
      in terms of its binding constants with 14- to 17-membered macrocycles. Employing
      Job's method of continuous variation established 1:1 stoichiometry for the
      interaction between Cu(II) and 1-5. From UV-Visible studies applying the Benesi
      Hildebrand equation, the binding constants (K) of Cu(II) with 1-5 were determined
      to be Cu(II)/1=3330 (+/-321) dm(3) mol(-1), Cu(II)/2=33,700 (+/-71) dm(3) mol(
      1), Cu(II)/3=7260 (+/-151) dm(3) mol(-1), Cu(II)/4=57,000 (+/-257) dm(3) mol(-1)
      and Cu(II)/5=13,900 (+/-398) dm(3) mol(-1) in methanol at 25 degrees C,
      respectively. The calculated binding constants showed a saw-tooth pattern in
      which 4 (18-membered ring) gives the highest K value for these complexes. The
      thermodynamic parameters (DeltaG, DeltaH, and TDeltaS) of the respective
      complexes have also been determined.

PMID- 25574646
TI  - Photocatalytic degradation and antimicrobial applications of F-doped MWCNTs/TiO2
      composites.
AB  - Multi-walled carbon nanotubes-fluorine-co-doped TiO2 composite was synthesized by
      the solid state method. The prepared photocatalysts were characterized by using
      XRD, FTIR and FE-SEM. In addition, the samples were evaluated for antimicrobial
      activity and photocatalytic activity. The composites exhibited enhanced
      absorption properties in the UV light range compared to pure TiO2. The MWCNTS-F
      co-doped TiO2 composites showed significant photocatalytic activity in the
      generation of oxygen. 

PMID- 25574647
TI  - Selective recognition of 6-mercaptopurine based on luminescent metal-organic
      frameworks Fe-MIL-88NH2.
AB  - A novel and rapid spectrofluorometry method for the recognition of 6
      mercaptopurine (6-MP) has been developed based on luminescent metal-organic
      frameworks Fe-MIL-88NH2 as fluorescent probe. The strong fluorescence of Fe-MIL
      88NH2 at 430 nm could be quenched by 6-MP directly, and the Fe-MIL-88NH2 shows
      high selectivity for 6-MP compared to other thiol-containing amino acids such as
      homocysteine (Hcy), cysteine (Cys), glutathione (GSH), etc. Under optimal
      conditions, the relative fluorescence intensity was linearly proportional to the
      concentration of 6-MP in the range of 5-600 MUM with the detection limit at 1.17
      MUM (S/N=3). Furthermore, the present approach has been successfully applied to
      the determination of 6-MP in human serum samples. The possible fluorescence
      quenching mechanism has also been investigated, where it is revealed that the
      quenching was attributed to competition of absorption of the light source energy
      as well as electron transfer between Fe-MIL-88NH2 and 6-MP.

PMID- 25574648
TI  - Synthesis, growth, structural and optical studies of a novel organic Piperazine
      (bis) p-toluenesulfonate single crystal.
AB  - A novel organic single crystal of Piperazinium (bis) p-toluenesulfonate (PPTS)
      was grown by a slow evaporation solution growth technique. The structure of the
      grown crystal was determined using single crystal X-ray diffraction analysis. The
      PPTS crystal belongs to the triclinic crystal system with space group of P1-. The
      presence of functional groups was confirmed by FTIR spectral analysis. The
      optical transmittance range and cut-off wavelength were identified by UV-vis-NIR
      spectral studies. The luminescent properties of PPTS crystal were investigated.
      The thermal behavior of PPTS crystal was studied by TG-DT analyses. 

PMID- 25574649
TI  - A novel one-dimensional manganese(II) coordination polymer containing both
      dicyanamide and pyrazinamide ligands: synthesis, spectroscopic investigations, X
      ray studies and evaluation of biological activities.
AB  - A novel 1D coordination polymer {[Mn(MU1,5-dca)2(PZA)2](PZA)2}n, 1, has been
      synthesized and characterized by single crystal X-ray crystallography. The
      coordination mode of dicyanamide (dca) and pyrazinamide (PZA) ligands was
      inferred by IR spectroscopy. The compound 1 was evaluated for in vitro
      antimycobacterial and antitumor activities. It demonstrated better in vitro
      activity against Mycobacterium tuberculosis than pyrazinamide and its MIC value
      was determined. Complex 1 was also screened for its in vitro antitumor activity
      towards LM3 and LP07 murine cancer cell lines. In addition, the antibacterial
      activity of complex 1 has been tested against Gram(+) and Gram(-) bacteria and it
      has shown promising broad range anti-bacterial activity. 

PMID- 25574650
TI  - Spectroscopic studies of heat-treated FeNxCy/C involved in electrochemical oxygen
      reduction under acid media.
AB  - Carbon-incorporated FeNx electrocatalysts (FeNC/C-T) have been synthesized by
      carbonizing a nitrogen-containing specie and iron precursor on carbon blacks at
      various heat-treated temperatures. The catalyst properties (crystalline
      structure, surface chemical states, oxidation state and co-ordination geometry)
      and their formation scheme of FeNC/C-T have been thoroughly examined by X-ray
      based spectroscopies such as X-ray diffraction, X-ray photoelectron spectroscopy
      (XPS) and X-ray absorption spectroscopy (XAS). The electrochemical performance of
      oxygen reduction reaction (ORR) and methanol tolerance were also investigated by
      rotating disk electrode tests in 0.5M H2SO4. By combined results from XPS and XAS
      spectroscopies, the catalysts carbonized at 1073K possess higher surface Fe/C and
      N/C atomic ratios with formation of carbons incorporated FeN4 species were found
      to have the optimal electrocatalytic properties. 

PMID- 25574651
TI  - Conformational analysis, X-ray crystallographic, FT-IR, FT-Raman, DFT, MEP and
      molecular docking studies on 1-(1-(3-methoxyphenyl) ethylidene)
      thiosemicarbazide.
AB  - Conformational analysis, X-ray crystallographic, FT-IR, FT-Raman, DFT, MEP and
      molecular docking studies on 1-(1-(3-methoxyphenyl) ethylidene) thiosemicarbazide
      (MPET) are investigated. From conformational analysis the examination of the
      positions of a molecule taken and the energy changes is observed. The docking
      studies of the ligand MPET with target protein showed that this is a good
      molecule which docks well with target related to HMG-CoA. Hence MPET can be
      considered for developing into a potent anti-cholesterol drug. MEP assists in
      optimization of electrostatic interactions between the protein and the ligand.
      The MEP surface displays the molecular shape, size and electrostatic potential
      values. The optimized geometry of the compound was calculated from the DFT-B3LYP
      gradient calculations employing 6-31G (d, p) basis set and calculated vibrational
      frequencies are evaluated via comparison with experimental values. 

PMID- 25574652
TI  - A rhodamine-benzothiazole conjugated sensor for colorimetric, ratiometric and
      sequential recognition of copper(II) and sulfide in aqueous media.
AB  - A new rhodamine-benzothiazole conjugated colorimetric sensor 1 that exhibits
      sequential recognition to Cu(2+) and S(2-) in CH3CN/HEPES buffer (v/v=1:1, HEPES
      10mM, pH=7.0) solution has been developed. Sensor 1 displays highly selective and
      sensitive recognition to Cu(2+) with a ratiometric behavior, and the resultant 1
      Cu(2+) complex can act as a highly selective S(2-) sensor via Cu(2+) displacement
      approach. The Cu(2+) and S(2-) recognition processes are rapid and reversible,
      and the Cu(2+) and S(2-) inputs can result in an INHIBIT logic gate. 

PMID- 25574653
TI  - A colorimetric probe based on desensitized ionene-stabilized gold nanoparticles
      for single-step test for sulfate ions.
AB  - Desensitized ionene-stabilized gold nanoparticles have been prepared and applied
      as a colorimetric probe for the single-step test for sulfate ions at the
      relatively high concentration level. The approach is based on aggregation of the
      nanoparticles leading to the change in absorption spectra and color of the
      solution. These nanoparticles are characterized by the decreased sensitivity due
      to both electrostatic and steric stabilization, which allows for simple, and
      rapid direct single-step determination of sulfate at the relatively high
      concentration level in real water samples without sample pretreatment or
      dilution. Influence of different factors (the time of interaction, pH, the
      concentrations of sulfate ions and the nanoparticles) on the aggregation and
      analytical performance of the procedure was investigated. The method allows for
      the determination of sulfate ions in the mass range of 0.2-0.4 mg with RSD of 5%
      from the sample volume of less than 2 mL. It has a sharp dependence of the
      colorimetric response on the concentration of sulfate, which makes it prospective
      for indicating deviations of the sulfate concentration regarding some declared
      value chosen within the above range. The time of the analysis is 2 min. The
      method was applied to the analysis of mineral water samples.

PMID- 25574654
TI  - Electrolytic coloration below 100 degrees C and spectral properties of potassium
      alum crystals.
AB  - Potassium alum crystals are colored electrolytically below 100 degrees C and
      under various voltages using a pointed cathode and a flat anode. SO3(-), SO2(-),
      O3(-), O2(-), O(-) hole-trapped centers and O(0), O(2-), H(+) radicals are
      produced in colored potassium alum crystals. No obvious characteristic absorption
      band in ultraviolet and visible wavelength regions is observed in absorption
      spectrum of uncolored potassium alum crystal. Characteristic absorption bands of
      SO3(-), SO2(-) and O3(-) hole-trapped centers are observed in the absorption
      spectra of the colored potassium alum crystals. The hole-trapped centers and
      radicals come from electric- and thermal-induced decomposition of SO4(2-)
      radicals and crystalline water molecules. Current-time curve for electrolytic
      coloration of potassium alum crystal is given. Electron exchanges from electrons
      and small charged radicals to electrodes induce complete current. 

PMID- 25574655
TI  - Conformational and spectroscopic study of xanthogen ethyl formates,
      ROC(S)SC(O)OCH2CH3. Isolation of CH3CH2OC(O)SH.
AB  - ROC(S)SC(O)OCH2CH3, with R=CH3-, (CH3)2CH- and CH3(CH2)2-, were obtained through
      the reaction between potassium xanthate salts, ROC(S)SK, and ethyl chloroformate,
      ClC(O)OCH2CH3. The liquid compounds were identified and characterized by (1)H and
      (13)C NMR and mass spectrometry. The conformations adopted by the molecules were
      studied by DFT methods. 6 conformers were theoretically predicted for R=CH3- and
      (CH3)2CH-, while the conformational flexibility of the n-propyl substituent
      increases the total number of feasible rotamers to 21. For the three molecules,
      the conformers can be associated in 3 groups, being the most stable the AS forms 
      the C=S double bond anti (A) with respect to the C-S single bond and the S-C
      single bond syn (S) with respect to the C=O double bond - followed by AA and SS
      conformers. The vibrational spectra were interpreted in terms of the predicted
      conformational equilibrium, presenting the nu(C=O) spectral region signals
      corresponding to the three groups of conformers. A moderated pre-resonance Raman
      enhancement of the nu(C=S) vibrational mode of CH3(CH2)2OC(S)SC(O)OCH2CH3 was
      detected, when the excitation radiation approaches the energy of a n->pi*
      electronic transition associated with the C=S chromophore. UV-visible spectra in
      different solvents were measured and interpreted in terms of TD-DFT calculations.
      The unknown molecule CH3CH2OC(O)SH was isolated by the UV-visible photolysis of
      CH3OC(S)SC(O)OCH2CH3 isolated in Ar matrix, and also obtained as a side-product
      of the reaction between potassium xanthate salts, ROC(S)SK, and ethyl
      chloroformate, ClC(O)OCH2CH3.

PMID- 25574656
TI  - The new Schiff base 4-[(4-Hydroxy-3-fluoro-5-methoxy-benzylidene)amino]-1,5
      dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one: experimental, DFT calculational
      studies and in vitro antimicrobial activity.
AB  - The synthesized Schiff base, 4-[(4-Hydroxy-3-fluoro-5-methoxy-benzylidene)amino]
      1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one (I), has been characterized by
      (13)C NMR, (1)H NMR, 2D NMR ((1)H-(1)H COSY and (13)C APT), FT-IR, UV-vis and X
      ray single-crystal techniques. Molecular geometry of the compound I in the ground
      state, vibrational frequencies and chemical shift values have been calculated by
      using the density functional method (DFT) with 6-311++G(d,p) basis set. The
      obtained results indicate that optimized geometry can well reflect the crystal
      structural parameters. The differences between experimental and calculated
      results of FT-IR and NMR have supported the existence of intermolecular (O-H?O
      type) and intramolecular (C-H?O type) hydrogen bonds in the crystal structure.
      Molecular electrostatic potential (MEP), frontier molecular orbital analysis
      (HOMO-LUMO) and electronic absorption spectra were carried out at B3LYP/6
      311G++(d,p). HOMO-LUMO electronic transition of 3.92eV is due to contribution of
      the bands the n->pi*. The antimicrobial activity of the compound I was determined
      against the selected 11 bacteria and 8 fungi by microdilution broth assay with
      Alamar Blue. In vitro studies showed that the compound I has no antifungal effect
      for selected fungal isolates. However, the compound I shows remarkable
      antibacterial effect for the bacteria; Streptococcus pneumoniae, Haemophilus
      influenzae and Enterococcus faecalis.

PMID- 25574657
TI  - Green synthesis, spectroscopic investigation and photocatalytic activity of lead
      nanoparticles.
AB  - Most of researcher focused their research towards synthesize of nanoparticles by
      the method of applied chemical method which was one of the costliest method. We
      have focused cheapest and simplest method for the synthesizing of lead
      nanoparticles (Pb-NPs) using cocos nucifera L extract. The methanolic extract of
      cocos nucifera L was efficiently used as a reducing agent for synthesizing Pb
      NPs. On treatment of lead acetate with cocos nucifera coir extracts, stable Pb
      NPs were formed. The synthesized Pb-NPs were further confirmed by UV-visible
      spectroscopy, X-ray diffraction (XRD), Transmission electron microscope (TEM) and
      Energy Dispersive (EDAX) analysis. The secondary metabolites present in
      methanolic extract which can mainly act as a reducing and capping agents for the
      formation of Pb-NPs were identified by GC-MS. Anti-microbial activity for Pb-NPs
      against four pathogenic strain's such as Staphylococcus aureus, Escheria coli,
      Staphylococcus epidermis and Bacillus subtilis. Result states that Pb-NPs size
      was 47 nm and also shows good activity against S. aureus. Further we report on
      photocatalytic absorption of malachite green dye processed in short UV wavelength
      at 254 nm. UV spectral analysis showed peak absorbance at 613 nm with special
      reference to the excitation of surfaces plasmon vibration by Pb-NPs.

PMID- 25574658
TI  - A sensitive and selective chemiluminescence sensor for the determination of
      dopamine based on silanized magnetic graphene oxide-molecularly imprinted
      polymer.
AB  - Based on silanized magnetic graphene oxide-molecularly imprinted polymer (Si-MG
      MIP), a sensitive and selective chemiluminescence sensor for dopamine measurement
      was developed. Si-MG-MIP, in which silanes was introduced to improve the mass
      transfer, graphene oxide was employed to improve absorption capacity, Fe3O4
      nanoparticles were applied for separation easily and molecularly imprinted
      polymer was used to improve selectivity, demonstrated the advantages of the
      sensor. All the composites were confirmed by SEM, TEM, XRD and FTIR. Under the
      optimal conditions of chemiluminescence, dopamine could be assayed in the range
      of 8.0-200.0 ng/mL with a correlation coefficient of linear regression of 0.9970.
      The detection limit was 1.5 ng/mL (3delta) and the precision for 11 replicate
      detections of 80.0 ng/mL dopamine was 3.4% (RSD). When the sensor was applied in
      determining dopamine in actual samples, recovery ranged from 94% to 110%, which
      revealed that the results were satisfactory.

PMID- 25574659
TI  - Use of primary high-risk human papillomavirus testing for cervical cancer
      screening: interim clinical guidance.
AB  - In 2011, the American Cancer Society, the American Society for Colposcopy and
      Cervical Pathology, and the American Society for Clinical Pathology updated
      screening guidelines for the early detection of cervical cancer and its
      precursors. Recommended screening strategies were cytology or cotesting (cytology
      in combination with high-risk HPV (hrHPV) testing). These guidelines also
      addressed the use of hrHPV testing alone as a primary screening approach, which
      was not recommended for use at that time. There is now a growing body of evidence
      for screening with primary hrHPV testing, including a prospective US-based
      registration study. Thirteen experts including representatives from the Society
      of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology,
      American College of Obstetricians and Gynecologists, American Cancer Society,
      American Society of Cytopathology, College of American Pathologists, and the
      American Society for Clinical Pathology, convened to provide interim guidance for
      primary hrHPV screening. This guidance panel was specifically triggered by an
      application to the FDA for a currently marketed HPV test to be labeled for the
      additional indication of primary cervical cancer screening. Guidance was based on
      literature review and review of data from the FDA registration study,
      supplemented by expert opinion. This document aims to provide information for
      health care providers who are interested in primary hrHPV testing and an overview
      of the potential advantages and disadvantages of this strategy for screening as
      well as to highlight areas in need of further investigation. 

PMID- 25574660
TI  - Hovering on the threshold of change.

PMID- 25574661
TI  - Quantitative detection of eryptosis in human erythrocytes using tunable resistive
      pulse sensing and annexin-V-beads.
AB  - Toxicological assessments of human red blood cells (RBCs) are important in human
      health because RBCs are the most abundant cell type in our body.
      Erythrotoxicology testing guidelines using hemolysis have been established as a
      standard (e.g. by the ASTM International). However, many xenobiotics promote
      eryptosis (apoptosis in human RBCs) without causing hemolysis. Based on the major
      features of eryptosis, i.e. cell shrinkage and translocation of
      phosphatidylserine (PS) to the outer lipid bilayer of the plasma membrane, we
      report here a novel approach utilizing the quantitative tunable resistive pulse
      sensing (TRPS) technology, a widely adopted technique for characterizing
      nanoparticles in the field of nanotechnology, to measure the degree of eryptosis
      in a non-optical manner. With the TRPS system, we were able to determine PS
      externalization with microbeads functionalized with annexin-V for PS binding,
      cell swelling and shrinkage in physiological buffers (cell volume: 86 +/- 12 fL)
      and solutions of different osmolarities with or without apoptotic trigger. After
      setting these standards, we then evaluated the toxicity of Polyphyllin D (PD), a
      potential anti-cancer drug that kills more liver cancer cells with multi-drug
      resistance, in erythrocytes to prove our concept. Data revealed that PD induced
      PS externalization and shrinkage in RBCs in a dose-dependent manner. Moreover,
      another feature of eryptosis, as small as 5 fL, was detected thus showing the PD
      induced erythrotoxicity in human cells. Taken together, our results indicate that
      our approach using annexin-V-beads and TRPS is simple, safe and convenient, using
      only a small volume (35 MUL) to evaluate the erythrotoxicity of xenobiotics. 

PMID- 25574662
TI  - Simulation guided design of globular single-chain nanoparticles by tuning the
      solvent quality.
AB  - The control of primary and further structures of individual folded/collapsed
      synthetic polymers has received significant attention in recent years. However,
      the synthesis of single-chain nanoparticles (SCNPs) showing a compact, globular
      conformation in solution has turned out so far to be highly elusive. By means of
      simulations, we propose two methods for obtaining globular SCNPs in solution. The
      first synthesis route is performed in the bad solvent, with the precursor
      anchored to a surface. In the second route we use a random copolymer precursor
      with unreactive solvophilic and reactive solvophobic units, which form a single
      core-shell structure. Both protocols prevent intermolecular cross-linking. After
      recovering good solvent conditions, the swollen nanoparticles maintain their
      globular character. The proposed methods are experimentally realizable and do not
      require specific sequence control of the precursors. Our results pave the way for
      the synthesis via solvent-assisted design of a new generation of globular soft
      nanoparticles mimicking global conformations of native proteins in solution. 

PMID- 25574663
TI  - A statistical comparison of active and passive ammonia measurements collected at
      Clean Air Status and Trends Network (CASTNET) sites.
AB  - Atmospheric concentrations of ammonia (NH3) are not well characterized in the
      United States due to the sparse number of monitors, the relatively short lifetime
      of NH3 in the atmosphere, and the difficulty in measuring non-point source
      emissions such as fertilized agricultural land. In this study, we compare
      measured weekly concentrations of NH3 collected by two denuder systems with a bi
      weekly passive NH3 sampler used by the National Atmospheric Deposition Program's
      (NADP) Ammonia Monitoring Network (AMoN). The purpose of the study was to verify
      the passive samplers used by AMoN and characterize any uncertainties introduced
      when using a bi-weekly versus weekly sampling time period. The study was
      conducted for 1 year at five remote Clean Air Status and Trends Network (CASTNET)
      sites. Measured ambient NH3 concentrations ranged from 0.03 MUg NH3 m(-3) to 4.64
      MUg NH3 m(-3) in upstate New York and northwest Texas, respectively, while dry
      deposition estimates ranged from 0.003 kg N ha(-1) wk(-1) to 0.47 kg N ha(-1) wk(
      1). Results showed that the bi-weekly passive samplers performed well compared to
      annular denuder systems (ADS) deployed at each of the five CASTNET sites, while
      the MetOne Super SASS Mini-Parallel Plate Denuder System (MPPD) was biased low
      when compared to the ADS. The mean relative percent difference (MRPD) between the
      ADS and MPPD and the ADS and AMoN sampler was -38% and -9%, respectively.
      Precision of the ADS and MPPD was 5% and 13%, respectively, while the precision
      of the passive samplers was 5%. The results of this study demonstrate that the
      NH3 concentrations measured by AMoN are comparable to the ADS and may be used to
      supplement the high-time resolution measurements to gain information on spatial
      gradients of NH3, long-term trends and seasonal variations in NH3 concentrations.

PMID- 25574664
TI  - Association of acute adverse effects with high local SAR induced in the brain
      from prolonged RF head and neck hyperthermia.
AB  - To provide an adequate level of protection for humans from exposure to radio
      frequency (RF) electromagnetic fields (EMF) and to assure that any adverse health
      effects are avoided. The basic restrictions in terms of the specific energy
      absorption rate (SAR) were prescribed by IEEE and ICNIRP. An example of a
      therapeutic application of non-ionizing EMF is hyperthermia (HT), in which
      intense RF energy is focused at a target region. Deep HT in the head and neck
      (H&N) region involves inducing energy at 434 MHz for 60 min on target. Still,
      stray exposure of the brain is considerable, but to date only very limited side
      effects were observed. The objective of this study is to investigate the
      stringency of the current basic restrictions by relating the induced EM dose in
      the brain of patients treated with deep head and neck (H&N) HT to the scored
      acute health effects. We performed a simulation study to calculate the induced
      peak 10 g spatial-averaged SAR (psSAR10g) in the brains of 16 selected H&N
      patients who received the highest SAR exposure in the brain, i.e. who had the
      minimum brain-target distance and received high forwarded power during treatment.
      The results show that the maximum induced SAR in the brain of the patients can
      exceed the current basic restrictions (IEEE and ICNIRP) on psSAR10g for
      occupational environments by 14 times. Even considering the high local SAR in the
      brain, evaluation of acute effects by the common toxicity criteria (CTC) scores
      revealed no indication of a serious acute neurological effect. In addition, this
      study provides pioneering quantitative human data on the association between
      maximum brain SAR level and acute adverse effects when brains are exposed to
      prolonged RF EMF.

PMID- 25574666
TI  - Correction: serum reference values for leptin in healthy infants.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0113024.]. 

PMID- 25574665
TI  - Combining gene mutation with gene expression data improves outcome prediction in
      myelodysplastic syndromes.
AB  - Cancer is a genetic disease, but two patients rarely have identical genotypes.
      Similarly, patients differ in their clinicopathological parameters, but how
      genotypic and phenotypic heterogeneity are interconnected is not well understood.
      Here we build statistical models to disentangle the effect of 12 recurrently
      mutated genes and 4 cytogenetic alterations on gene expression, diagnostic
      clinical variables and outcome in 124 patients with myelodysplastic syndromes.
      Overall, one or more genetic lesions correlate with expression levels of ~20% of
      all genes, explaining 20-65% of observed expression variability. Differential
      expression patterns vary between mutations and reflect the underlying biology,
      such as aberrant polycomb repression for ASXL1 and EZH2 mutations or perturbed
      gene dosage for copy-number changes. In predicting survival, genomic,
      transcriptomic and diagnostic clinical variables all have utility, with the
      largest contribution from the transcriptome. Similar observations are made on the
      TCGA acute myeloid leukaemia cohort, confirming the general trends reported here.

PMID- 25574667
TI  - Seasonality of fire weather strongly influences fire regimes in South Florida
      savanna-grassland landscapes.
AB  - Fire seasonality, an important characteristic of fire regimes, commonly is
      delineated using seasons based on single weather variables (rainfall or
      temperature). We used nonparametric cluster analyses of a 17-year (1993-2009)
      data set of weather variables that influence likelihoods and spread of fires
      (relative humidity, air temperature, solar radiation, wind speed, soil moisture)
      to explore seasonality of fire in pine savanna-grassland landscapes at the Avon
      Park Air Force Range in southern Florida. A four-variable, three-season model
      explained more variation within fire weather variables than models with more
      seasons. The three-season model also delineated intra-annual timing of fire more
      accurately than a conventional rainfall-based two-season model. Two seasons
      coincided roughly with dry and wet seasons based on rainfall. The third season,
      which we labeled the fire season, occurred between dry and wet seasons and was
      characterized by fire-promoting conditions present annually: drought, intense
      solar radiation, low humidity, and warm air temperatures. Fine fuels consisting
      of variable combinations of pyrogenic pine needles, abundant C4 grasses, and
      flammable shrubs, coupled with low soil moisture, and lightning ignitions early
      in the fire season facilitate natural landscape-scale wildfires that burn uplands
      and across wetlands. We related our three season model to fires with different
      ignition sources (lightning, military missions, and prescribed fires) over a 13
      year period with fire records (1997-2009). Largest wildfires originate from
      lightning and military ignitions that occur within the early fire season
      substantially prior to the peak of lightning strikes in the wet season.
      Prescribed ignitions, in contrast, largely occur outside the fire season. Our
      delineation of a pronounced fire season provides insight into the extent to which
      different human-derived fire regimes mimic lightning fire regimes. Delineation of
      a fire season associated with timing of natural lightning ignitions should be
      useful as a basis for ecological fire management of humid savanna-grassland
      landscapes worldwide. 

PMID- 25574669
TI  - Unilateral ectopic mammary-like tissue in the vulva.

PMID- 25574668
TI  - Dynamics of actin waves on patterned substrates: a quantitative analysis of
      circular dorsal ruffles.
AB  - Circular Dorsal Ruffles (CDRs) have been known for decades, but the mechanism
      that organizes these actin waves remains unclear. In this article we
      systematically analyze the dynamics of CDRs on fibroblasts with respect to
      characteristics of current models of actin waves. We studied CDRs on
      heterogeneously shaped cells and on cells that we forced into disk-like
      morphology. We show that CDRs exhibit phenomena such as periodic cycles of
      formation, spiral patterns, and mutual wave annihilations that are in accord with
      an active medium description of CDRs. On cells of controlled morphologies, CDRs
      exhibit extremely regular patterns of repeated wave formation and propagation,
      whereas on random-shaped cells the dynamics seem to be dominated by the limited
      availability of a reactive species. We show that theoretical models of reaction
      diffusion type incorporating conserved species capture partially the behavior we
      observe in our data. 

PMID- 25574670
TI  - Menopausal hormone therapy and quality of life: too many pyjamas.

PMID- 25574671
TI  - Perceptions of a night float system of resident call within an obstetrics and
      gynaecology residency training program.
AB  - OBJECTIVE: To determine the attitudes of residents, attending obstetricians, and
      nursing staff members towards night float resident call, compared with a
      traditional 24-hour call system. METHODS: In June 2012, obstetrics and
      gynaecology residents at the University of Toronto who had participated in both a
      night float and a 24-hour call system were asked to complete an electronic
      survey. Attending obstetricians and nurses in the labour and delivery unit at two
      tertiary care hospitals with a night float system of resident call completed
      electronic and paper surveys, respectively. Questions asked respondents to
      compare the two systems of call with respect to resident morale, fatigue, and
      continuity of care, and to indicate which system of call they preferred. RESULTS:
      Surveys were completed by 20/24 residents (83%), 24/39 attending obstetricians
      (62%) and 47/58 nurses (81%). Most residents reported less fatigue (17/20, 85%)
      and improved continuity of care (15/20, 75%) while doing night float call, but
      morale was mixed. Overall, 14/20 (70%) residents preferred the night float
      system. Staff perceptions of resident night float call were mixed in all areas,
      and most reported no difference in resident morale (17/24, 71%). Nurses found
      residents were less fatigued (32/47, 68%) and easier to work with (34/47, 72%),
      and felt that night float call improved continuity of care (37/47, 79%).
      CONCLUSION: Resident attitudes towards night float call are mostly positive.
      Attitudes of attending obstetricians are mixed, but nurses prefer this system of
      resident call.

PMID- 25574672
TI  - The incidence of maternal artefact during intrapartum fetal heart rate
      monitoring.
AB  - OBJECTIVE: To determine the incidence of maternal heart rate artefact (MHRA) when
      monitoring fetal heart rate (FHR) in labour and to determine obstetrical factors
      associated with MHRA. METHODS: In a prospective observational study, maternal and
      fetal heart rates were displayed simultaneously to document the superimposition
      of the maternal heart rate (MHR) on FHR tracings. All women in labour who were
      undergoing external fetal monitoring (EFM) at the Ottawa Hospital from October
      2011 to March 2012 were eligible. Every episode of MHRA was documented and
      classified according to its clinical significance. Wilcoxon test, t tests, and
      chi-square tests were used to identify time-related differences and obstetrical
      factors (epidural analgesia, fetal presentation, multiple gestation, maternal
      BMI, umbilical cord arterial pH, five-minute Apgar scores) that were associated
      with a potential adverse outcome. RESULTS: We assessed 1313 tracings with
      simultaneous displays of the MHR and FHR in labour. MHRA was present at least
      once in 721 tracings (55%). Of these tracings, 35 were classified as having one
      or more episodes that might have led to an adverse outcome (either false positive
      or false negative), giving an incidence of 2.7% of all women in labour. In 33
      tracings, the MHRA masked an abnormal FHR tracing. In two tracings, the MHRA
      masked a normal FHR, which might have resulted in misinterpretation of the
      tracing (i.e., false positive), leading to unnecessary intervention. CONCLUSION:
      The incidence of MHRA is higher than currently thought, and in more than 2% of
      women in labour may lead to adverse outcomes. We propose routine use of
      simultaneous maternal and FHR monitoring for women undergoing EFM, especially
      during the second stage of labour.

PMID- 25574673
TI  - Abdominal adiposity and insulin resistance in early pregnancy.
AB  - BACKGROUND: High pre-pregnancy body mass index is a known risk factor for
      gestational diabetes mellitus, but the contribution of abdominal adiposity to
      insulin resistance (IR) in pregnancy is not well understood. We assessed the
      association between abdominal adiposity in early pregnancy and IR. METHODS: We
      completed a prospective cohort study of 79 pregnant women. Visceral adipose
      tissue (VAT) depth was measured by ultrasonography at 11 to 14 weeks' gestation,
      at the time of routine fetal nuchal translucency assessment. A two-hour 75 g oral
      glucose tolerance test was subsequently completed at 16 to 22 weeks' gestation
      and IR was estimated by the homeostatic model assessment of insulin resistance
      (HOMA-IR) as well as by the insulin sensitivity index. RESULTS: After adjusting
      for maternal age, parity, ethnicity, and pre-pregnancy BMI, VAT depth explained
      42% of the variance in HOMA-IR, which was slightly better than the variance in
      the multivariable model examining HOMA-IR and pre-pregnancy BMI (40%). For the
      insulin sensitivity index, the model variance values were 36% and 32%,
      respectively. CONCLUSION: Measurement of maternal adipose tissue depth at the
      time of routine first-trimester ultrasonography may provide additional
      information about maternal IR, beyond pre-pregnancy BMI.

PMID- 25574674
TI  - A randomized, double-blind, placebo-controlled study to evaluate the effects of
      alendronate on bone mineral density and bone remodelling in perimenopausal women
      with low bone mineral density.
AB  - BACKGROUND: Perimenopausal women can experience rapid bone loss at skeletal sites
      with both cortical and cancellous bone, increasing the prevalence of osteoporosis
      following menopause. METHODS: We conducted a 12-month randomized placebo
      controlled trial evaluating the effects of alendronate 70 mg with 2800 IU
      cholecalciferol administered once per week for 12 months in comparison with
      placebo and cholecalciferol. The primary end-point was the percentage change in
      the lumbar spine bone mineral density (BMD) from baseline to 12 months. Secondary
      end-points were the change in BMD at the femoral neck and changes in biochemical
      markers of bone turnover. RESULTS: Forty-five women were recruited to participate
      in the study. Five subjects withdrew from the study before randomization for
      unrelated reasons. Forty subjects were randomly allocated to the alendronate and
      placebo groups. The mean lumbar spine MD in women treated with alendronate
      increased by 3.66% (mean paired difference, MUd = 0.032; +/- 0.008 SE) at 12
      months, compared with a reduction of 3.33% (MUd = -0.030; +/- 0.008 SE) in the
      control group (P < 0.001). In the femoral neck, the mean BMD in the alendronate
      group increased by 2.07% (MUd = 0.014; +/- 0.009 SE) at 12 months, compared with
      a reduction of 1.87% (MUd = -0.014; +/- 0.008 SE) in the control group (P =
      0.046). There were no differences in BMD between the alendronate and placebo
      groups at the total hip sites after 12 months. At 12 months, both bone-specific
      alkaline phosphatase and urinary N-telopeptide were significantly reduced, by
      37.79% (MUd = -9.90; +/- 1.92 SE) and 27.21% (MUd = -11.68; +/- 4.80 SE)
      respectively, in the alendronate group; in the control group, these levels
      increased (P < 0.001). CONCLUSION: Weekly treatment with alendronate 70 mg and
      cholecalciferol 2800 IU increases BMD and decreases bone turnover in
      perimenopausal women.

PMID- 25574675
TI  - Post-uterine artery embolization pain and clinical outcomes for symptomatic
      myomas using gelfoam pledgets alone versus embospheres plus gelfoam pledgets: a
      comparative pilot study.
AB  - BACKGROUND: To evaluate the efficacy and post-procedural pain associated with
      uterine artery embolization (UAE) using Gelfoam alone versus Embospheres plus
      Gelfoam in women with symptomatic uterine fibroids. METHOD: We conducted a
      prospective, non-randomized pilot study. Fluoroscopy-guided trans-femoral artery
      UAE was performed using Gelfoam pledgets alone or Embospheres (500 to 700 mg)
      plus Gelfoam under conscious sedation and local anaesthesia. This was followed by
      patient-controlled analgesia (PCA) using a morphine pump overnight. Post
      procedural pain was assessed by the mean amount of self-administered morphine
      delivered by PCA pump (mL) from 0 to 19 hours in each group. The mean volumes of
      the uterus and the dominant fibroid were calculated by ultrasound at baseline,
      three months, six months, and 12 months. RESULTS: A total of 17 women
      participated in the study. Bilateral uterine artery occlusion was performed in
      eight women using Gelfoam alone, and in nine women using Embosphere + Gelfoam.
      One woman in the Embosphere + Gelfoam group developed a puncture-site hematoma
      requiring further intervention one week later. The mean (SD) amount of morphine
      self-administered by PCA pump at time 0, 1, and 2 hours was 3.4 mg (3.1), 2.9 mg
      (2.2), and 2.4 mg (3.3) in the Gelfoam-only group and 6.1 mg (3.0), 9.6 mg (7.1),
      and 5.3 mg (4.4) in the Embosphere + Gelfoam group, respectively. After three
      hours, the amount of morphine used was equal in both groups. The mean (SD) total
      dose of morphine used was 29.5 mg (18.6) in the Gelfoam group and 41.1 mg (19.3)
      in the Embosphere + Gelfoam group (P = 0.228). At 12 months, the reduction in
      median total uterine volume and median dominant fibroid volume in each group was
      equal. CONCLUSION: Clinical outcomes were equivalent after uterine artery
      embolization using Gelfoam alone versus Gelfoam + Embospheres. Although the
      amount of immediate post-procedure pain may be less with Gelfoam alone, we could
      not demonstrate this objectively using morphine use as a measure of pain.

PMID- 25574676
TI  - The effect of age, ethnicity, and level of education on fertility awareness and
      duration of infertility.
AB  - OBJECTIVE: An increasing number of Canadian women are delaying child-bearing,
      despite a decrease in fertility with age. A longer duration of infertility is
      associated with a significant decrease in live birth rate, reinforcing the need
      for prompt access to fertility treatment. This study aimed to assess the
      fertility awareness of women attending a fertility clinic to determine whether
      fertility awareness is a factor in accessing treatment. METHODS: A quantitative
      cross-sectional survey evaluated fertility awareness and collected information
      about ethnicity, education level, and the duration of infertility for new
      patients. Fertility awareness was evaluated with questions about prevalence,
      causes, and treatment of infertility. RESULTS: The mean age of participants in
      the study was 34 years (range 23 to 44; n = 140). The duration of infertility
      before new patients first sought medical advice for infertility was less than one
      year in 52.9%, one to two years in 28.6%, two to three years in 12.9%, and four
      or more years in 5.0% of study participants. Fertility awareness was calculated
      as the percentage of correct responses to the survey questions. The mean
      fertility awareness for all study participants was 49.9% and this ranged from the
      lowest score of 9.1% to the highest score of 90.9% correct. Women waiting for
      longer than two years to seek medical help had lower fertility awareness (P =
      0.038). In addition, fertility awareness was greater in women who had previously
      sought medical help for infertility from a family doctor, a gynaecologist, or
      another fertility clinic (P = 0.001). Higher fertility awareness correlated with
      a higher level of education (linear trend P < 0.001). Finally, fertility
      awareness also varied with ethnicity (ANOVA P = 0.025), but the age at which
      women of different ethnicities sought treatment was similar (ANOVA P = 0.13).
      CONCLUSION: Fertility awareness is associated with time to seek treatment,
      ethnicity, and level of education among new patients seeking medical treatment.
      This study demonstrates the need to educate women of reproductive age and
      identifies particular patient populations in Canada that would most benefit from
      further education about infertility.

PMID- 25574677
TI  - Curettage and Asherman's syndrome-lessons to (re-) learn?
AB  - OBJECTIVE: To investigate the noted cluster of cases of Asherman's syndrome in an
      18-month period at an Early Pregnancy Assessment Centre at a tertiary care
      institution. METHODS: A practice audit was performed involving (a) a detailed
      chart review of the six index cases; and (b) compilation of treatment choices for
      all new patient referrals in the same 18-month time frame from July 2011 to
      December 2012. Diagnosis of Asherman's syndrome was made with a combination of
      clinical menstrual symptoms and hysteroscopic diagnosis of intrauterine
      adhesions. RESULTS: Of 1580 new patient referrals, 884 chose one of four forms of
      active management for early pregnancy failure. Six women (6/844, 0.7%) were
      subsequently found to have Asherman's syndrome. All six women (100%) underwent
      sharp curettage, and three (50%) had repeat curettage performed. No cases of
      Asherman's were reported following manual vacuum aspiration (0/191) or medical
      management with misoprostol (0/210). CONCLUSION: Asherman's syndrome remains a
      risk for those undergoing dilatation and curettage for management of spontaneous
      abortion and should be an important component of the informed consent for this
      procedure. Both sharp and repeated curettage remain important risk factors and
      should be employed judiciously. The evaluation of the common risk factors
      associated with these cases could target changes in practice.

PMID- 25574679
TI  - Incidental endometrial carcinoma diagnosed at first trimester pregnancy loss: a
      case report.
AB  - BACKGROUND: All cases reported to date of endometrioid endometrial adenocarcinoma
      (EEA) associated with pregnancy have been treated surgically or medically. We
      describe a case of EEA in pregnancy that was managed expectantly, allowing for
      observation of the natural course of the disease. CASE: A 36-year-old woman,
      gravida 2 para 1, presented at eight weeks of pregnancy with heavy vaginal
      bleeding. Ultrasound assessment confirmed a missed abortion, and the patient
      underwent dilatation and curettage. Tissue pathology primarily suggested grade 1
      EEA. The patient chose expectant management. Eight months later, she returned
      with vaginal bleeding. Hysterectomy was performed and the hysterectomy specimen
      showed FIGO grade 1 stage 1A EEA. CONCLUSION: Treating EEA associated with
      pregnancy is challenging. Our experience in the case described here suggests that
      expectant management should not be undertaken due to a high risk of recurrence.

PMID- 25574678
TI  - Pelvic floor tenderness in the etiology of superficial dyspareunia.
AB  - OBJECTIVE: To calculate the prevalence of pelvic floor tenderness in the
      population of women with pelvic pain and to determine its implications for
      symptoms of pelvic pain. METHODS: We conducted a retrospective review of patients
      with pelvic pain at a tertiary referral centre. Pelvic floor tenderness was
      defined as levator ani tenderness on at least one side during single digit pelvic
      examination. The prevalence of pelvic floor tenderness in this cohort of women
      with pelvic pain was compared with the prevalence in a cohort of women without
      pain attending a gynaecology clinic. In the women with pelvic pain, multiple
      regression was performed to determine which variables were independently
      associated with pelvic floor tenderness. RESULTS: The prevalence of pelvic floor
      tenderness was 40% (75/189) in the cohort with pelvic pain, significantly greater
      than the prevalence of 13% (4/32) in the cohort without pain (OR 4.61; 95% CI
      1.55 to 13.7, P = 0.005). On multiple logistic regression, superficial
      dyspareunia (OR 4.45; 95% CI 1.86 to 10.7, P = 0.001), abdominal wall pain (OR
      4.04; 95% CI 1.44 to 11.3, P = 0.005), and bladder base tenderness (OR 4.65; 95%
      CI 1.87 to 11.6, P = 0.001) were independently associated with pelvic floor
      tenderness. Pelvic floor tenderness was similarly present in women with or
      without underlying endometriosis. CONCLUSION: Pelvic floor tenderness is common
      in women with pelvic pain, with or without endometriosis, and is a contributor to
      superficial dyspareunia. Pelvic floor tenderness was also associated with
      abdominal wall pain and bladder base tenderness, suggesting that nervous system
      sensitization is involved in the etiology of pelvic floor tenderness.

PMID- 25574680
TI  - Assessment tool for total laparoscopic hysterectomy: a Delphi consensus survey
      among international experts.
AB  - OBJECTIVE:  To achieve consensus among experts on the essentials steps to include
      in an assessment tool for total laparoscopic hysterectomy.  METHODS:  Using a
      Delphi consensus process, an initial survey was created based on the current
      literature and local expertise in laparoscopic surgery and sent to international
      experts in laparoscopic gynaecology. Experts were selected according to specific
      criteria. A second survey was formulated based on the answers and comments from
      the first round and sent to all experts who participated in the first round.
      Consensus was defined as a Cronbach alpha >= 0.80. A rate of agreement >= 0.70
      was used to define which substeps to keep in the final tool. RESULTS:  From the
      85 experts invited to participate, 53 (62%) agreed to participate, and 51 of
      these participated in both rounds. The final instrument to assess total
      laparoscopic hysterectomy was created using the items with a high level of
      agreement after two rounds. This final tool showed good internal consistency
      among the experts, with a Cronbach alpha of 0.90. CONCLUSION:  Using a Delphi
      methodology, we achieved international consensus among experts in laparoscopic
      gynaecology within a short time frame and with minimal costs. The resulting
      evaluation tool for total laparoscopic hysterectomy may serve in the assessment
      of surgical skills in the future, and would be a valuable adjunct to postgraduate
      training and continuing medical education programs. This tool will now undergo a
      validation process, comparing the rating scores of novices and experts surgeons.

PMID- 25574682
TI  - Synthesis and polymerase-mediated bypass studies of the N2-deoxyguanosine DNA
      damage caused by a lucidin analogue.
AB  - Lucidin is a genotoxic and mutagenic hydroxyanthraquinone metabolite, which
      originates from the roots of Rubia tinctorum L. (madder root). It reacts with
      exocyclic amino groups of DNA nucleobases and forms adducts/lesions leading to
      carcinogenesis. To study the effect of lucidin-induced DNA damage, herein, we
      report the first synthesis of a structural analogue of lucidin [N(2)-methyl-(1,3
      dimethoxyanthraquinone)-deoxyguanosine, LdG] embedded DNAs utilizing
      phosphoramidite strategy. LdG modification in a DNA duplex imparts
      destabilization (DeltaTm ~5  degrees C/modification), which is attributed to the
      unfavorable contribution from the enthalpy. Primer extension studies using the
      Klenow fragment (exo(-)) of Escherichia coli DNA polymerase I demonstrate that
      bypass of LdG modification is error prone as well as slow compared to that across
      the unmodified sites. Molecular dynamics simulations of the binary complex of
      Bacillus fragment polymerase (homologue of the Klenow fragment) and LdG-DNA
      duplex elucidate the structural fluctuations imparted by the LdG lesion, as well
      as the molecular mechanism of bypass at the lesion site. Overall, the results
      presented here show that the lucidin adduct destabilizes DNA structure and
      reduces fidelity and processivity of DNA synthesis. 

PMID- 25574683
TI  - Peptide nanofiber complexes with siRNA for deep brain gene silencing by
      stereotactic neurosurgery.
AB  - Peptide nanofibers (PNFs) are one-dimensional assemblies of amphiphilic peptides
      in a cylindrical geometry. We postulated that peptide nanofibers (PNFs) can
      provide the tools for genetic intervention and be used for delivery of siRNA, as
      they can be engineered with positively charged amino acids that can
      electrostatically bind siRNA. The aim of this work was to investigate the use of
      PNFs as vectors for siRNA delivery providing effective gene knockdown. We
      designed a surfactant-like peptide (palmitoyl-GGGAAAKRK) able to self-assemble
      into PNFs and demonstrated that complexes of PNF:siRNA are uptaken
      intracellularly and increase the residence time of siRNA in the brain after
      intracranial administration. The biological activity of the complexes was
      investigated in vitro by analyzing the down-regulation of the expression of a
      targeted protein (BCL2), as well as induction of apoptosis, as well as in vivo by
      analyzing the relative gene expression upon stereotactic administration into a
      deep rat brain structure (the subthalamic nucleus). Gene expression levels of
      BCL2 mRNA showed that PNF:siBCL2 constructs were able to silence the target BCL2
      in specific loci of the brain. Silencing of the BCL2 gene resulted in ablation of
      neuronal cell populations, indicating that genetic interventions by PNF:siRNA
      complexes may lead to novel treatment strategies of CNS pathologies. 

PMID- 25574681
TI  - The prevention of ovarian hyperstimulation syndrome.
AB  - OBJECTIVE: To review the clinical aspects of ovarian hyperstimulation syndrome
      and provide recommendations on its prevention. OPTIONS: Preventative measures,
      early recognition, and prompt systematic supportive care will help avoid poor
      outcomes. OUTCOMES: Establish guidelines to assist in the prevention of ovarian
      hyperstimulation syndrome, early recognition of the condition when it occurs, and
      provision of appropriate supportive measures in the correct setting. EVIDENCE:
      Published literature was retrieved through searches of Medline, Embase, and the
      Cochrane Library from 2011 to 2013 using appropriate controlled vocabulary
      ([OHSS] ovarian hyperstimulation syndrome and: agonist IVF, antagonist IVF,
      metformin, HCG, gonadotropin, coasting, freeze all, agonist trigger,
      progesterone) and key words (ovarian hyperstimulation syndrome, ovarian
      stimulation, gonadotropin, human chorionic gonadotropin, prevention). Results
      were restricted to systematic reviews, randomized control trials/controlled
      clinical trials, and observational studies published in English. There were no
      date restrictions. Searches were updated on a regular basis and incorporated in
      the guideline to February 2013. Grey (unpublished) literature was identified
      through searching the websites of health technology assessment and health
      technology-related agencies, clinical practice guideline collections, clinical
      trial registries, and national and international medical specialty societies.
      VALUES: The quality of evidence in this document was rated using the criteria
      described in the Report of the Canadian Task Force on Preventive Health Care
      (Table 1). Summary Statements 1. The particular follicle-stimulating hormone
      formulation used for ovarian stimulation does not affect the incidence of ovarian
      hyperstimulation syndrome. (I) 2. Coasting may reduce the incidence of severe
      ovarian hyperstimulation syndrome. (III) 3. Coasting for longer than 3 days
      reduces in vitro fertilization pregnancy rates. (II-2) 4. The use of either
      luteinizing hormone or human chorionic gonadotropin for final oocyte maturation
      does not influence the incidence of ovarian hyperstimulation syndrome. (I) 5.
      There is no clear published evidence that lowering the human chorionic
      gonadotropin dose will result in a decrease in the rate of ovarian
      hyperstimulation syndrome. (III) 6. Cabergoline starting from the day of human
      chorionic gonadotropin reduces the incidence of ovarian hyperstimulation syndrome
      in patients at higher risk and does not appear to lower in vitro fertilization
      pregnancy rates. (II-2) 7. Avoiding pregnancy by freezing all embryos will
      prevent severe prolonged ovarian hyperstimulation syndrome in patients at high
      risk. (II-2) 8. Pregnancy rates are not affected when using gonadotropin
      releasing hormone (GnRH) agonists in GnRH antagonist protocols for final egg
      maturation when embryos are frozen by vitrification for later transfer. (II-2)
      Recommendations 1. The addition of metformin should be considered in patients
      with polycystic ovarian syndrome who are undergoing in vitro fertilization
      because it may reduce the incidence of ovarian hyperstimulation syndrome. (I-A)
      2. Gonadotropin dosing should be carefully individualized, taking into account
      the patient's age, body mass, antral follicle count, and previous response to
      gonadotropins. (II-3B) 3. Cycle cancellation before administration of human
      chorionic gonadatropin is an effective strategy for the prevention of ovarian
      hyperstimulation syndrome, but the emotional and financial burden it imposes on
      patients should be considered before the cycle is cancelled. (III-C) 4.
      Gonadotropin-releasing hormone (GnRH) antagonist stimulation protocols are
      recommended in patients at high risk for ovarian hyperstimulation syndrome
      (OHSS). The risk of severe OHSS in patients on GnRH antagonist protocols who have
      a very robust ovarian stimulation response can be reduced by using a GnRH agonist
      as a substitute for human chorionic gonadotropin to trigger final oocyte
      maturation. (I-B) 5. A gonadotropin-releasing hormone (GnRH) antagonist protocol
      with a GnRH agonist trigger for final oocyte maturation is recommended for donor
      oocyte and fertility preservation cycles. (III-C) 6. Albumin or other plasma
      expanders at the time of egg retrieval are not recommended for the prevention of
      ovarian hyperstimulation syndrome. (I-E) 7. Elective single embryo transfer is
      recommended in patients at high risk for ovarian hyperstimulation syndrome. (III
      C) 8. Progesterone, rather than human chorionic gonadotropin, should be used for
      luteal phase support. (I-A) 9. Outpatient culdocentesis should be considered for
      the prevention of disease progression in severe ovarian hyperstimulation
      syndrome. (II-2B).

PMID- 25574684
TI  - Combining an ionic transition metal complex with a conjugated polymer for wide
      range voltage-controlled light-emission color.
AB  - We report on voltage-controlled electroluminescence (EL) over a broad range of
      colors from a "two-luminophor" (2L) light-emitting electrochemical cell (LEC),
      comprising a blend of a majority blue-emitting conjugated polymer (blue-CP), a
      minority red-emitting ionic transition metal complex (red-iTMC), and an ion
      transporting compound as the active layer. The EL color is reversibly shifted
      from red, over orange, pink, and white, to blue by simply changing the applied
      voltage from 3 to 7 V. An analysis of our results suggests that the low
      concentration of immobile cations intrinsic to this particular device
      configuration controls the electron injection and thereby the EL color: at low
      voltage, electrons are selectively injected into the low-barrier minority red
      iTMC, but with increasing voltage the injection into the high-barrier majority
      blue-CP is gradually improved. 

PMID- 25574685
TI  - Measurement of Vitamin K1 in Commercial Canola Cultivars from Growing Locations
      in North and South America Using High-Performance Liquid Chromatography-Tandem
      Mass Spectrometry.
AB  - Plant oils, including canola oil, are considered to be major sources of vitamin K
      as the second most substantial contributor of vitamin K to the human diet. Green
      leafy vegetables are the largest source of vitamin K. However, the effects of
      environment and germplasm on vitamin K levels in harvested canola seed have not
      been extensively investigated. To better understand these relationships,
      harvested canola seed from a range of diverse cultivars grown in different
      geographical locations in North and South America was assessed for levels of
      vitamin K. The analytical method developed to perform this measurement was based
      on C30 reversed-phase HPLC that could distinguish the biologically active trans
      vitamin K1 from the inactive cis-isomer. Results demonstrated that for the
      majority of the canola cultivars evaluated, those cultivated in the North
      American sites had higher average vitamin K1 levels than those cultivated in the
      South American sites. Not all of the cultivars exhibited differences in response
      to the environment, suggesting that individual cultivar genetics also played a
      role in the variability of vitamin K1 levels observed in canola seed. Results
      from this study suggest that cultivar and environmental effects influence vitamin
      K1 levels in canola seed and provide a context to assess compositional
      variability of new cultivars.

PMID- 25574687
TI  - Family of class I lantibiotics from actinomycetes and improvement of their
      antibacterial activities.
AB  - Lantibiotics, an abbreviation for "lanthionine-containing antibiotics", interfere
      with bacterial metabolism by a mechanism not exploited by the antibiotics
      currently in clinical use. Thus, they have aroused interest as a source for new
      therapeutic agents because they can overcome existing resistance mechanisms.
      Starting from fermentation broth extracts preselected from a high-throughput
      screening program for discovering cell-wall inhibitors, we isolated a series of
      related class I lantibiotics produced by different genera of actinomycetes.
      Analytical techniques together with explorative chemistry have been used to
      establish their structures: the newly described compounds share a common 24 aa
      sequence with the previously reported lantibiotic planosporicin (aka 97518),
      differing at positions 4, 6, and 14. All of these compounds maintain an overall 
      1 charge at physiological pH. While all of these lantibiotics display modest
      antibacterial activity, their potency can be substantially modulated by
      progressively eliminating the negative charges, with the most active compounds
      carrying basic amide derivatives of the two carboxylates originally present in
      the natural compounds. Interestingly, both natural and chemically modified
      lantibiotics target the key biosynthetic intermediate lipid II, but the former
      compounds do not bind as effectively as the latter in vivo. Remarkably, the basic
      derivatives display an antibacterial potency and a killing effect similar to
      those of NAI-107, a distantly related actinomycete-produced class I lantibiotic
      which lacks altogether carboxyl groups and which is a promising clinical
      candidate for treating Gram-positive infections caused by multi-drug-resistant
      pathogens. 

PMID- 25574686
TI  - Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806)
      and clinical proof of concept in a human RSV challenge study.
AB  - GS-5806 is a novel, orally bioavailable RSV fusion inhibitor discovered following
      a lead optimization campaign on a screening hit. The oral absorption properties
      were optimized by converting to the pyrazolo[1,5-a]-pyrimidine heterocycle, while
      potency, metabolic, and physicochemical properties were optimized by introducing
      the para-chloro and aminopyrrolidine groups. A mean EC50 = 0.43 nM was found
      toward a panel of 75 RSV A and B clinical isolates and dose-dependent antiviral
      efficacy in the cotton rat model of RSV infection. Oral bioavailability in
      preclinical species ranged from 46 to 100%, with evidence of efficient
      penetration into lung tissue. In healthy human volunteers experimentally infected
      with RSV, a potent antiviral effect was observed with a mean 4.2 log10 reduction
      in peak viral load and a significant reduction in disease severity compared to
      placebo. In conclusion, a potent, once daily, oral RSV fusion inhibitor with the
      potential to treat RSV infection in infants and adults is reported. 

PMID- 25574688
TI  - Turning on catalysis: incorporation of a hydrogen-bond-donating squaramide moiety
      into a Zr metal-organic framework.
AB  - Herein, we demonstrate that the incorporation of an acidic hydrogen-bond-donating
      squaramide moiety into a porous UiO-67 metal-organic framework (MOF) derivative
      leads to dramatic acceleration of the biorelevant Friedel-Crafts reaction between
      indole and beta-nitrostyrene. In comparison, it is shown that free squaramide
      derivatives, not incorporated into MOF architectures, have no catalytic activity.
      Additionally, using the UiO-67 template, we were able to perform a direct
      comparison of catalytic activity with that of the less acidic urea-based
      analogue. This is the first demonstration of the functionalization of a
      heterogeneous framework with an acidic squaramide derivative. 

PMID- 25574690
TI  - Direct dynamics simulation of dissociation of the [CH3--I--OH]- ion-molecule
      complex.
AB  - Direct dynamics simulations were used to study dissociation of the [CH3--I--OH](
      ) complex ion, which was observed in a previous study of the OH(-) + CH3I gas
      phase reaction ( J. Phys. Chem. A 2013 , 117 , 7162 ). Restricted B97-1
      simulations were performed to study dissociation at 65, 75, and 100 kcal/mol and
      the [CH3--I--OH](-) ion dissociated exponentially, in accord with RRKM theory.
      For these energies the major dissociation products are CH3I + OH(-), CH2I(-) +
      H2O, and CH3OH + I(-). Unrestricted B97-1 and restricted and unrestricted CAM
      B3LYP simulations were also performed at 100 kcal/mol to compare with the
      restricted B97-1 results. The {CH3I + OH(-)}:{CH2I(-) + H2O}:{CH3OH + I(-)}
      product ratio is 0.72:0.15:0.13, 0.81:0.05:0.14, 0.71:0.19:0.10, and
      0.83:0.13:0.04 for the restricted B97-1, unrestricted B97-1, restricted CAM
      B3LYP, and unrestricted CAM-B3LYP simulations, respectively. Other product
      channels found are CH2 + I(-) + H2O, CH2 + I(-)(H2O), CH4 + IO(-), CH3(-) + IOH,
      and CH3 + IOH(-). The CH3(-) + IOH singlet products are only given by the
      restricted B97-1 simulation and the lower energy CH3 + IOH(-) doublet products
      are only formed by the unrestricted B97-1 simulation. Also studied were the
      direct and indirect atomic-level mechanisms for forming CH3I + OH(-), CH2I(-) +
      H2O, and CH3OH + I(-). The majority of CH3I + OH(-) were formed through a direct
      mechanism. For both CH2I(-) + H2O and CH3OH + I(-), the direct mechanism is
      overall more important than the indirect mechanisms, with the roundabout like
      mechanism the most important indirect mechanism at high excitation energies.
      Mechanism comparisons between the B97-1 and CAM-B3LYP simulations showed that
      formation of the CH3OH---I(-) complex is favored for the B97-1 simulations,
      whereas formation of the HO(-)---HCH2I complex is favored for the CAM-B3LYP
      simulations. The unrestricted simulations give a higher percentage of indirect
      mechanisms than the restricted simulations. The possible role of the self
      interaction error in the simulations is also discussed. The work presented here
      gives a detailed picture of the [CH3--I--OH](-) dissociation dynamics and is very
      important for unraveling the role of [CH3--I--OH](-) in the dynamics of the OH(
      )(H2O)(n=1,2) + CH3I reactions.

PMID- 25574689
TI  - New role for the ankyrin repeat revealed by a study of the N-formyltransferase
      from Providencia alcalifaciens.
AB  - N-Formylated sugars such as 3,6-dideoxy-3-formamido-d-glucose (Qui3NFo) have been
      observed on the lipopolysaccharides of various pathogenic bacteria, including
      Providencia alcalifaciens, a known cause of gastroenteritis. These unusual
      carbohydrates are synthesized in vivo as dTDP-linked sugars. The biosynthetic
      pathway for the production of dTDP-Qui3NFo requires five enzymes with the last
      step catalyzed by an N-formyltransferase that utilizes N(10)-tetrahydrofolate as
      a cofactor. Here we describe a structural and functional investigation of the P.
      alcalifaciens N-formyltransferase, hereafter referred to as QdtF. For this
      analysis, the structure of the dimeric enzyme was determined in the presence of
      N(5)-formyltetrahydrofolate, a stable cofactor, and dTDP-3,6-dideoxy-3-amino-d
      glucose (dTDP-Qui3N) to 1.5 A resolution. The overall fold of the subunit
      consists of three regions with the N-terminal and middle motifs followed by an
      ankyrin repeat domain. Whereas the ankyrin repeat is a common eukaryotic motif
      involved in protein-protein interactions, reports of its presence in prokaryotic
      enzymes have been limited. Unexpectedly, this ankyrin repeat houses a second
      binding pocket for dTDP-Qui3N, which is characterized by extensive interactions
      between the protein and the ligand. To address the effects of this second binding
      site on catalysis, a site-directed mutant protein, W305A, was constructed.
      Kinetic analyses demonstrated that the catalytic activity of the W305A variant
      was reduced by approximately 7-fold. The structure of the W305A mutant protein in
      complex with N(5)-formyltetrahydrofolate and dTDP-Qui3N was subsequently
      determined to 1.5 A resolution. The electron density map clearly showed that
      ligand binding had been completely abolished in the auxiliary pocket. The wild
      type enzyme was also tested for activity against dTDP-3,6-dideoxy-3-amino-d
      galactose (dTDP-Fuc3N) as a substrate. Strikingly, sigmoidal kinetics indicating
      homotropic allosteric behavior were observed. Although the identity of the ligand
      that regulates QdtF activity in vivo is at present unknown, our results still
      provide the first example of an ankyrin repeat functioning in small molecule
      binding. 

PMID- 25574691
TI  - Probing the excitonic states of site-controlled GaN nanowire quantum dots.
AB  - We report the detection of fully confined excited states and the zero-absorption
      region of individual site-controlled GaN/AlGaN nanowire quantum dots using
      photoluminescence excitation spectroscopy, which provides evidence of the true
      zero-dimensional discrete density of states of such quantum dots. Because of the
      strong quantum confinement in these dots, the p-shell, d-shell, and even higher
      energy (including some f-shell) states of a single quantum dot are observed,
      which provides unprecedented insight into the electronic structure. Several
      emitters are measured and used to build up an average picture of the electronic
      structure of a single quantum dot via comparison to theoretical simulations. 

PMID- 25574692
TI  - "Darker-than-black" PbS quantum dots: enhancing optical absorption of colloidal
      semiconductor nanocrystals via short conjugated ligands.
AB  - Colloidal quantum dots (QDs) stand among the most attractive light-harvesting
      materials to be exploited for solution-processed optoelectronic applications. To
      this aim, quantitative replacement of the bulky electrically insulating ligands
      at the QD surface coming from the synthetic procedure is mandatory. Here we
      present a conceptually novel approach to design light-harvesting nanomaterials
      demonstrating that QD surface modification with suitable short conjugated organic
      molecules permits us to drastically enhance light absorption of QDs, while
      preserving good long-term colloidal stability. Indeed, rational design of the
      pendant and anchoring moieties, which constitute the replacing ligand framework
      leads to a broadband increase of the optical absorbance larger than 300% for
      colloidal PbS QDs also at high energies (>3.1 eV), which could not be predicted
      by using formalisms derived from effective medium theory. We attribute such a
      drastic absorbance increase to ground-state ligand/QD orbital mixing, as inferred
      by density functional theory calculations; in addition, our findings suggest that
      the optical band gap reduction commonly observed for PbS QD solids treated with
      thiol-terminating ligands can be prevalently ascribed to 3p orbitals localized on
      anchoring sulfur atoms, which mix with the highest occupied states of the QDs.
      More broadly, we provide evidence that organic ligands and inorganic cores are
      inherently electronically coupled materials thus yielding peculiar chemical
      species (the colloidal QDs themselves), which display arising (opto)electronic
      properties that cannot be merely described as the sum of those of the ligand and
      core components. 

PMID- 25574693
TI  - Exploring the conformational variability in the heme b propionic acid side chains
      through the effect of a biological probe: a study of the isolated ions.
AB  - The iron(III) protoporphyrin IX complex with imidazole, a biologically relevant
      ligand, occupying an axial position, has been studied by infrared multiple photon
      dissociation (IRMPD) spectroscopy. The complex has been delivered in gas-phase by
      electrospray ionization (ESI), mass selected in an ion trap, and assayed by IRMPD
      spectroscopy in two complementary frequency regions. The fingerprint range (900
      1900 cm(-1)) has been scanned using the Orsay free-electron laser beamline
      (CLIO), while the X-H (X = C,N,O) stretching region (3000-3600 cm(-1)) has been
      inspected using a tabletop IR optical parametric oscillator/amplifier (OPO/OPA)
      laser source. DFT calculations have been performed to obtain a comprehensive
      pattern of the various potential conformers yielding optimized geometries,
      relative thermodynamic parameters, and respective IR spectra. The comparison
      between the IR spectra for representative conformers and the experimental IRMPD
      features suggests the coexistence of two families of conformers involving
      different degrees of folding and hydrogen bonding between the two propionic acid
      functionalities on the periphery of the protoporphyrin IX macrocycle in a ratio
      depending on environmental conditions such as ESI solvent and temperature. The
      observed conformational variability of the porphyrin substituents in the naked
      heme-imidazole complex is consistent with the fine-tuning of the reactivity
      properties of this important prosthetic group by the specific surroundings in the
      protein core. 

PMID- 25574694
TI  - The relevance of public health history.

PMID- 25574695
TI  - Some urgent social claims. 1907.

PMID- 25574696
TI  - The relationship of fetal and infant mortality to residential segregation: an
      inquiry into social epidemiology. 1949.

PMID- 25574698
TI  - Borrelli responds.

PMID- 25574701
TI  - Dietary Iron and Colorectal Cancer Risk: A Review of Human Population Studies.
AB  - Iron is an essential micronutrient that is involved in many redox processes and
      serves as an integral component in various physiological functions. However,
      excess iron can cause tissue damage through its pro-oxidative effects,
      potentiating the development of many diseases such as cancer through the
      generation of reactive oxidative species. The two major forms of iron in the diet
      are heme and nonheme iron, both of which are found in several different foods. In
      addition to natural food sources, intake of nonheme iron may also come from
      fortified foods or in supplement form. This review summarizes the results of
      human population studies that have examined the role of dietary iron (heme and
      nonheme), heme iron alone, and iron from supplements in colorectal
      carcinogenesis. 

PMID- 25574702
TI  - Evaluation of intracameral injection of ranibizumab and bevacizumab on the
      corneal endothelium by scanning electron microscopy.
AB  - PURPOSE: To evaluate the effects of intracameral injection of ranibizumab and
      bevacizumab on the corneal endothelium by scanning electron microscopy (SEM).
      METHODS: Twenty-eight female rabbits were randomly divided into four equal
      groups. Rabbits in groups 1 and 2 underwent intracameral injection of 1 mg/0.1 mL
      and 0.5 mg/0.05 mL ranibizumab, respectively; group 3 was injected with 1.25
      mg/0.05 mL bevacizumab. All three groups were injected with a balanced salt
      solution (BSS) into the anterior chamber of the left (fellow) eye. None of the
      rabbits in group 4 underwent an injection. Corneal thickness and intraocular
      pressure were measured before the injections, on the first day, and in the first
      month after injection. The rabbits were sacrificed and corneal tissues were
      excised in the first month after injection. Specular microscopy was used for the
      corneal endothelial cell count. Endothelial cell density was assessed and
      comparisons drawn between the groups and the control. Micrographs were recorded
      for SEM examination. The structure of the corneal endothelial cells, the
      junctional area of the cell membrane, the distribution of microvillus, and the
      cell morphology of the eyes that underwent intracameral injection of vascular
      endothelial growth factor (VEGF), BSS, and the control group were compared.
      RESULTS: Corneal thickness and intraocular pressure were not significantly
      different between the groups that underwent anti-VEGF or BSS injection and the
      control group on the first day and in the first month of injection. The corneal
      endothelial cell count was significantly diminished in all three groups;
      predominantly in group 1 and 2 (P<0.05). The SEM examination revealed normal
      corneal endothelial histology in group 3 and the control group. Eyes in group 1
      exhibited indistinctness of corneal endothelial cell borders, microvillus loss in
      the luminal surface, excessive blebbing, and disintegration of intercellular
      junctions. In group 2, the cell structure of the corneal endothelium and
      intercellular junctions were normal. However, a relative reduction was observed
      in the microvillus density of endothelial cells. Although eyes in group 3 were
      morphologically similar to fellow eyes and the control group, disarrangement in
      endothelial cell borders was evident. CONCLUSION: The SEM examination pointed out
      deterioration in endothelial cell morphology after intracameral injection of 1
      and 0.5 mg ranizumab. However, the effects of intracameral bevacizumab injection
      on corneal endothelial cells were similar to those found in fellow eyes and the
      control group. Further large-scale studies that examine the cellular changes by
      transmission electron microscopy are required to support the results of the
      present study that evaluates the structural changes in endothelial cells by SEM.

PMID- 25574705
TI  - High occurrence of food insecurity among urban Afghan refugees in Pakdasht, Iran
      2008: a cross-sectional study.
AB  - This research aimed to evaluate food security and its association with
      anthropometric measures among Afghan refugees living in Pakdasht, one of the main
      harbors of Afghan refugees in the neighborhood of Tehran. A total of 414
      registered Afghan refugee households were recruited in a cross-sectional study.
      About 88% of households were food insecure. Unemployment and socioeconomic status
      were the major determinants of food insecurity among the refugee households.
      While about 58% of women were overweight/obese, the prevalence of underweight and
      wasting were remarkable in children (11.0% and 12.7%, respectively), indicating a
      recent malnutrition. Government and organizations working for refugees must focus
      their activities on empowering Afghan refugees. 

PMID- 25574704
TI  - Maternal fuels and metabolic measures during pregnancy and neonatal body
      composition: the healthy start study.
AB  - CONTEXT: The impact of specific maternal fuels and metabolic measures during
      early and late gestation on neonatal body composition is not well defined.
      OBJECTIVE: To determine how circulating maternal glucose, lipids, and insulin
      resistance in the first and second halves of pregnancy influence neonatal body
      composition. DESIGN: A prospective pre-birth cohort enrolling pregnant women, the
      Healthy Start Study, was conducted, in which fasting maternal serum samples were
      collected twice during pregnancy to measure glucose, insulin, hemoglobin A1c,
      triglyceride, total cholesterol, high-density lipoprotein, and free fatty acids.
      Neonatal body composition was measured with air displacement plethysmography.
      SETTING: An observational epidemiology study of pregnant women attending
      obstetric clinics at the University of Colorado, Anschutz Medical Center.
      PARTICIPANTS: This analysis includes 804 maternal-neonate pairs. RESULTS: A
      strong positive linear relationship between maternal estimated insulin resistance
      (homeostasis model of assessment for insulin resistance) in the first half of
      pregnancy and neonatal fat mass (FM) and FM percentage (FM%) was detected,
      independent of prepregnancy body mass index (BMI). In the second half of
      pregnancy, positive linear relationships between maternal glucose levels and
      offspring FM and FM% were observed, independent of prepregnancy BMI. An inverse
      relationship was detected between high-density lipoprotein in the first half of
      pregnancy and FM, independent of prepregnancy BMI. Free fatty acid levels in the
      second half of pregnancy were positively associated with higher birth weight,
      independent of prepregnancy BMI. CONCLUSION: Maternal insulin resistance in the
      first half of pregnancy is highly predictive of neonatal FM%, whereas maternal
      glycemia, even within the normal range, is an important driver of neonatal
      adiposity in later pregnancy, independent of prepregnancy BMI. Our data provide
      additional insights on potential maternal factors responsible for fetal fat
      accretion and early development of adiposity.

PMID- 25574707
TI  - Biomechanical analysis of knee and trunk in badminton players with and without
      knee pain during backhand diagonal lunges.
AB  - The contribution of core neuromuscular control to the dynamic stability of
      badminton players with and without knee pain during backhand lunges has not been
      investigated. Accordingly, this study compared the kinematics of the lower
      extremity, the trunk movement, the muscle activation and the balance performance
      of knee-injured and knee-uninjured badminton players when performing backhand
      stroke diagonal lunges. Seventeen participants with chronic knee pain (injured
      group) and 17 healthy participants (control group) randomly performed two
      diagonal backhand lunges in the forward and backward directions, respectively.
      This study showed that the injured group had lower frontal and horizontal motions
      of the knee joint, a smaller hip-shoulder separation angle and a reduced trunk
      tilt angle. In addition, the injured group exhibited a greater left paraspinal
      muscle activity, while the control group demonstrated a greater activation of the
      vastus lateralis, vastus medialis and medial gastrocnemius muscle groups.
      Finally, the injured group showed a smaller distance between centre of mass (COM)
      and centre of pressure, and a lower peak COM velocity when performing the
      backhand backward lunge tasks. In conclusion, the injured group used reduced knee
      and trunk motions to complete the backhand lunge tasks. Furthermore, the
      paraspinal muscles contributed to the lunge performance of the individuals with
      knee pain, whereas the knee extensors and ankle plantar flexor played a greater
      role for those without knee pain. 

PMID- 25574708
TI  - Neurocognitive performance and behavioral symptoms in patients with attention
      deficit/hyperactivity disorder during twenty-four months of treatment with
      methylphenidate.
AB  - OBJECTIVE: This study investigated the trends in neurocognitive function and
      behavioral symptoms among patients with attention-deficit/hyperactivity disorder
      (ADHD) during 24 months of treatment with methylphenidate in a clinical setting.
      METHODS: Study participants consisted of 181 ADHD patients with a mean age of
      13.4+/-2.5 years (ages ranged from 8 to 18 years; 151 boys and 30 girls) who were
      prescribed oral short-acting methylphenidate two or three times daily, with each
      dose ranging between 0.3 and 1.0 mg/kg. At baseline and 6, 12, 18, and 24 months
      from baseline, neurocognitive function was assessed using the Test of Variables
      of Attention (TOVA) on the day the patient was off medication, and behavioral
      symptoms were evaluated using the Swanson, Nolan, and Pelham Version IV Scale for
      ADHD (SNAP-IV) parent form, the SNAP-IV teacher form, and the ADHD-Rating Scale
      (completed by a child psychiatrist). RESULTS: Of the 181 ADHD patients at the
      initial visit, 103 (56.9%) completed the study. During the 24-month
      methylphenidate treatment, only the commission errors in TOVA significantly
      improved; however, the omission errors, response time, response time variability,
      response sensitivity, and ADHD score did not. The behavioral symptoms of ADHD,
      observed by various informants, all declined substantially, and were
      significantly correlated with each other during the long-term follow-up. The
      severity of teacher ratings was lower than that of parent and psychiatrist
      ratings. However, the teacher-rated inattention symptoms showed the strongest
      correlations with TOVA performance. CONCLUSIONS: Findings suggest that
      neurocognitive deficits in ADHD patients, except inhibition ability, might be
      long lasting in realistic settings. In addition, obtaining behavior profile
      assessments from multiple informants, especially from teachers, is vital for
      establishing a complete understanding of ADHD patients.

PMID- 25574710
TI  - Top traits.

PMID- 25574711
TI  - To the editor.

PMID- 25574706
TI  - The role of hypothalamic mTORC1 signaling in insulin regulation of food intake,
      body weight, and sympathetic nerve activity in male mice.
AB  - Insulin action in the brain particularly the hypothalamus is critically involved
      in the regulation of several physiological processes, including energy
      homeostasis and sympathetic nerve activity, but the underlying mechanisms are
      poorly understood. The mechanistic target of rapamycin complex 1 (mTORC1) is
      implicated in the control of diverse cellular functions, including sensing
      nutrients and energy status. Here, we examined the role of hypothalamic mTORC1 in
      mediating the anorectic, weight-reducing, and sympathetic effects of central
      insulin action. In a mouse hypothalamic cell line (GT1-7), insulin treatment
      increased mTORC1 activity in a time-dependent manner. In addition,
      intracerebroventricular (ICV) administration of insulin to mice activated mTORC1
      pathway in the hypothalamic arcuate nucleus, a key site of central action of
      insulin. Interestingly, inhibition of hypothalamic mTORC1 with rapamycin reversed
      the food intake- and body weight-lowering effects of ICV insulin. Rapamycin also
      abolished the ability of ICV insulin to cause lumbar sympathetic nerve
      activation. In GT1-7 cells, we found that insulin activation of mTORC1 pathway
      requires phosphatidylinositol 3-kinase (PI3K). Consistent with this, genetic
      disruption of PI3K in mice abolished insulin stimulation of hypothalamic mTORC1
      signaling as well as the lumbar sympathetic nerve activation evoked by insulin.
      These results demonstrate the importance of mTORC1 pathway in the hypothalamus in
      mediating the action of insulin to regulate energy homeostasis and sympathetic
      nerve traffic. Our data also highlight the key role of PI3K as a link between
      insulin receptor and mTORC1 signaling in the hypothalamus. 

PMID- 25574712
TI  - The crown to implant ratio in fixed prosthodontics.

PMID- 25574713
TI  - Achieving and maintaining apical patency in endodontics: optimizing canal shaping
      procedures.

PMID- 25574714
TI  - Why the general dentist needs to know how to manage oral lichen planus.
AB  - Oral lichen planus (OLP) is a frequently mismanaged chronic disease that requires
      care throughout a patient's life, and therefore a condition the general dentist
      must know how to manage. Patients with OLP often suffer considerable physical
      discomfort and an inability to perform proper oral hygiene, eventually resulting
      in poor periodontal health. In addition, these patients are confronted with the
      psychological stress of knowing that OLP is not curable. This is accompanied by a
      fear of other negative health developments, particularly oral cancer. The
      objective of this study was to identify major issues surrounding the management
      of OLP by the general dentist. A literature review of over 1100 articles was
      performed. An eclectic compilation of the issues revealed 12 major areas of
      concern. This article reviews those concerns and presents strategies for coping
      with the myriad signs, symptoms, and complications associated with this disease,
      as well as educational approaches and legal considerations. A rationale is
      provided to place the responsibility for the management of these patients under
      the person best positioned to coordinate care for this condition--the general
      dentist. A general dentist can contribute to the overall oral health of an OLP
      patient with timely diagnosis, effective treatment, thorough patient education,
      and the orchestration of efforts by a team of health care providers.

PMID- 25574715
TI  - Investigation of antibacterial efficacy of Acacia nilotica against salivary
      mutans streptococci: a randomized control trial.
AB  - This double-blind, randomized control trial sought to evaluate the clinical
      effects of 3 mouthrinses against salivary mutans streptococci (MS). Ninety high
      caries risk volunteers were randomly assigned to 3 groups, each group using a
      selected mouthrinse BID for 30 days. Subjects in Group 1 rinsed with 10 ml of 50%
      Acacia nilotica, Group 2 subjects rinsed with 10 ml of 0.2% chlorhexidine (active
      control), and subjects in Group 3 rinsed with saline water (passive control).
      Unstimulated saliva samples were collected at baseline, 30, and 60 days. MS were
      cultured on mitis salivarius bacitracin agar, and colony counts were obtained.
      The margin of error was fixed at 5%. ANOVA and post hoc least significant
      difference tests were performed. There were significant decreases in the MS
      colony count in the A. nilotica and chlorhexidine groups at 30 days (85% and 83%,
      respectively) and at 60 days (65% and 63%, respectively) (P < 0.0001). The
      antibacterial action of A. nilotica against MS was similar to that of
      chlorhexidine.

PMID- 25574716
TI  - Clinical considerations for selecting implant abutments for fixed prosthodontics.
AB  - There is an overwhelming number of designs and components for dentists to choose
      from when treatment planning implant-supported restorations. The selection
      process can be simplified by establishing priorities on a site-by-site basis to
      facilitate a predictable, esthetic, and stable final result. Clinical
      considerations should include prosthetic support, periodontal stability,
      reparability, and oral hygiene, which often occur in concert. This article
      addresses the principles that guide implant abutment selection when treatment
      planning for fixed prosthodontics.

PMID- 25574717
TI  - Surgical repair of invasive cervical root resorption with calcium-enriched
      mixture cement: a case report.
AB  - Invasive cervical resorption (ICR) occurs in the cervical area of the teeth due
      to the formation of a soft tissue that progressively resorbs dentin. The disease
      is asymptomatic unless the pulp is exposed. This article presents a case
      involving a mandibular canine that was treated with a calcium-enriched mixture
      (CEM) cement. After a full mucoperiosteal flap was performed, the soft tissue was
      curetted away and the cavity filled with CEM biomaterial. One week later, the
      supragingival surface of the CEM was polished and covered with composite resin.
      At a 1-year follow-up visit, the pulp was healthy and the gingival probing depth
      decreased from >3 mm to 1 mm, showing attachment gain. As a biocompatible
      material, CEM has proven its ability in dentinogenesis, cementogenesis, and
      osteogenesis; it may prove to be a suitable biomaterial for treating ICR cases.

PMID- 25574718
TI  - Evaluation of 3 dental unit waterline contamination testing methods.
AB  - Previous studies have found inconsistent results from testing methods used to
      measure heterotrophic plate count (HPC) bacteria in dental unit waterline (DUWL)
      samples. This study used 63 samples to compare the results obtained from an in
      office chairside method and 2 currently used commercial laboratory HPC methods
      (Standard Methods 9215C and 9215E). The results suggest that the Standard Method
      9215E is not suitable for application to DUWL quality monitoring, due to the
      detection of limited numbers of heterotrophic organisms at the required 35
      degrees C incubation temperature. The results also confirm that while the in
      office chairside method is useful for DUWL quality monitoring, the Standard
      Method 9215C provided the most accurate results.

PMID- 25574719
TI  - Local anesthetic calculations: avoiding trouble with pediatric patients.
AB  - Local anesthetic systemic toxicity (LAST) is a rare but avoidable consequence of
      local anesthetic overdose. This article will review the mechanism of action of
      local anesthetic toxicity and the signs and symptoms of LAST. Due to physiologic
      and anatomic differences between children and adults, LAST occurs more frequently
      in children; particularly when 3% mepivacaine is administered. The calculation of
      the maximum recommended dose based on mg/lb body weight, Clark's rule, and the
      Rule of 25 in order to prevent LAST will also be reviewed, as well as the
      appropriate treatment procedures for a local anesthetic overdose.

PMID- 25574720
TI  - The role of the dentist in identifying missing and unidentified persons.
AB  - The longer a person is missing, the more profound the need for dental records
      becomes. In 2013, there were >84,000 missing persons and >8,000 unidentified
      persons registered in the National Crime Information Center (NCIC) database. Tens
      of thousands of families are left without answers or closure, always maintaining
      hope that their relative will be located. Law enforcement needs the cooperation
      of organized dentistry to procure dental records, translate their findings, and
      upload them into the NCIC database for cross-matching with unidentified person
      records created by medical examiner and coroner departments across the United
      States and Canada.

PMID- 25574721
TI  - Nonsurgical endodontic treatment of permanent maxillary incisors with immature
      apex and a large periapical lesion: a case report.
AB  - Immature teeth with necrotic pulp and large periapical lesions are difficult to
      treat via conventional endodontic therapy. However, they can be treated with
      calcium hydroxide and mineral trioxide aggregate (MTA). This article reports the
      case of a nonvital tooth with a periapical lesion and an open apex that was
      treated with a single-visit MTA apical plug. A radiographic evaluation taken 6
      months post-treatment showed a decrease in the periapical lesion; at 1 year,
      complete healing was visible.

PMID- 25574722
TI  - Stress analysis of mandibular implant-retained overdenture with independent
      attachment system: effect of restoration space and attachment height.
AB  - In this in vitro study, 2 implants were embedded in the interforaminal region of
      an acrylic model. Two kinds of retention mechanisms were used to construct
      complete overdentures: ball type and direct abutment (Locator). The ball-type
      retention mechanism models included 3 different collar heights (1, 2, and 3 mm)
      with 15 mm occlusal plane height, and 3 different occlusal plane heights (9, 12,
      and 15 mm) with 1 mm collar height. The direct abutment models included 3
      different occlusal plane heights (9, 12, and 15 mm) with 1 mm cuff height.
      Vertical unilateral and bilateral loads of 150 N were applied to the central
      fossa of the first molar. The stress of the bone around the implant was analyzed
      by finite element analysis. The results showed that by increasing vertical
      restorative space, the maximum stress values around implants were decreased in
      both unilateral and bilateral loading models. The results also showed that the
      increase in maximum stress values around implants correlated with the ball
      attachment collar height. The Locator attachment with a 1 mm cuff height and 9 mm
      occlusal plane height demonstrated 6.147 and 3.914 MPa in unilateral and
      bilateral loading conditions, respectively. While a reduction in the collar
      height of a ball-type retention mechanism and an increase in the vertical
      restorative space in direct abutment retention mechanisms are both
      biomechanically favorable, and may result in reduced stress in peri-implant bone,
      a ball attachment seems to be more favorable in the stress distribution around an
      implant than a Locator attachment.

PMID- 25574723
TI  - p53 expression in oral lichenoid lesions and oral lichen planus.
AB  - The aim of this article was to compare the expression of p53 protein in oral
      lichen planus (OLP) and oral lichenoid reaction (OLR). The study population
      consisted of 65 patients--31 diagnosed with OLP and 34 with OLR. The results
      showed more p53 positive cases in the OLP group than in the OLR group. However,
      the difference between the 2 groups was not statistically significant (P =
      0.114). The most common immunolocalization was observed at the basal cell layer.
      Due to the chance of potential future malignancy, follow-up for all cases is
      recommended.

PMID- 25574724
TI  - Effect of imaging powders on the bond strength of resin cement.
AB  - The application and incomplete removal of a computer-aided design/computer-aided
      manufacture imaging powder may affect the dentin surface prior to bonding a
      ceramic restoration. The purpose of this study was to compare the effect of
      imaging powder residue on the shear bond strength of a self-adhesive resin cement
      to dentin. Mounted human third molars were sectioned coronally with a diamond saw
      to expose the dentin, which was then prepared with a diamond bur mounted in a
      custom jig. The dentin surface was sprayed with 3 different imaging powders. The
      3 powder groups were then divided into 3 subgroups based on the method of powder
      removal: no rinse, 1-second rinse, and 10-second rinse. A control group was
      created that had no application of imaging powder. A self-adhesive resin cement
      was bonded to the surfaces and loaded to failure in a universal testing machine
      after 24 hours of storage. Data was analyzed with Kruskal-Wallis and Mann-Whitney
      nonparametric tests. The bonding to dentin surfaces of the powder groups that
      were rinsed for 1 or 10 seconds were not significantly different from each other
      or the nonpowdered control. The type of imaging powder did not significantly
      affect the bond strength. The nonrinsed powdered dentin surface had a significant
      reduction in bond strength compared to both the control and the rinsed powdered
      surfaces. 

PMID- 25574725
TI  - Crestal approach for removing a migrated dental implant from the maxillary sinus:
      a case report.
AB  - This article reports a rare case of a horizontally displaced dental implant that
      migrated into the maxillary sinus 6 months after 3 implants were inserted into
      the augmented maxillary posterior region. Migration of dental implants into the
      maxillary sinus usually occurs during surgery and can result in serious
      complications.

PMID- 25574726
TI  - Ameloblastic carcinoma of the mandible manifesting as an infected odontogenic
      cyst.
AB  - Ameloblastic carcinoma (AC) is a rare malignant odontogenic tumor. Although most
      ACs appear to originate de novo, some cases originate from a pre-existing
      ameloblastoma. This article presents the case of a 69-year-old man with an AC in
      the left body of the mandible. Radiographically, the lesion resembled an
      odontogenic cyst surrounding an impacted tooth. While ACs tend to have aggressive
      features that distinguish them from their benign counterparts, some are more
      subtle in their presentation. Therefore, it is important that dentists rule out
      malignancy in lesions that do not display obvious radiographic features. 

PMID- 25574727
TI  - Apical plug technique in a calcified immature tooth: a case report.
AB  - Traumatic injury to an immature tooth may result in pulpal necrosis secondary to
      pulp canal obliteration, which makes the management of the tooth a clinical
      challenge for dentists. The present case report describes an innovative apical
      plug technique with mineral trioxide aggregate in a calcified immature tooth
      using an ultrasonic tip and long, thin, tapered fissure burs. The technique was
      proven to be successful clinically and radiographically at 2 years
      postobturation.

PMID- 25574728
TI  - Central giant cell lesion: diagnosis to rehabilitation.
AB  - Central giant cell lesion (CGCL) is a benign bone lesion of unknown etiology that
      primarily affects the mandible, with a predilection for female children and young
      adults. This article describes a case of a 16-year-old boy with a palatal
      swelling of approximately 18 months duration. Clinical, radiographic,
      histopathological, and hematological examinations led to a diagnosis of CGCL.
      Treatment involved a complete enucleation of the lesion and the removal of
      several teeth. A subsequent esthetic/functional rehabilitation was performed
      using a removable prosthesis. The patient was submitted to rigorous clinical and
      radiographic follow-ups, with no signs of recurrence over a 7-year period.

PMID- 25574729
TI  - Alveolar ridge splitting for implant placement: a review of the procedure and
      report of 3 cases.
AB  - In long-standing edentulous cases, the alveolar bone generally demonstrates
      vertical and horizontal atrophy. Rehabilitating these patients with dental
      implants is difficult unless treatment is accompanied by some kind of
      augmentation procedures, all of which include specific disadvantages. One such
      technique, alveolar ridge splitting, is suitable only for enhancing ridge width.
      It has the advantage of reducing treatment time significantly, as implants can be
      placed simultaneously. This article offers a brief description of the procedure
      along with 3 case reports. 

PMID- 25574730
TI  - Management of severe mandibular deviation following partial mandibular resection:
      a case report.
AB  - Extensive mandibular resection commonly leads to a deviation of the mandible,
      facial disfigurement, and difficulty with speech and mastication. The
      rehabilitation of these patients is a prosthodontic challenge. This article
      presents the case of a 60-year-old man who sought prosthetic rehabilitation after
      a right segmental mandibulectomy. The prosthetic rehabilitation was planned in 2
      phases. A palatal ramp was constructed, followed by a mandibular guiding flange.
      After 4 months, the patient's chewing ability, tongue movement, and facial
      esthetics were improved. 

PMID- 25574731
TI  - Rare oral cartilaginous choristoma: a case report and review of the literature.
AB  - Cartilaginous choristomas are extraosseous benign tumors. They occur in abnormal
      sites that usually do not contain chondrocytes. The oral variant of this entity
      is considered to be very rare, with only 38 cases currently published in the
      literature. This article presents a case of an oral cartilaginous choristoma
      lesion. In addition to presenting clinical and histological diagnoses, this
      article compares the present case to recently reported cases. Special attention
      was given to analyzing cells of the oral cartilaginous choristoma, which appear
      as well-differentiated chondrocytes with a pale blue cytoplasm surrounded by a
      light basophilic stroma and no evidence of malignity. Following surgical
      excision, the lesion did not recur, which is similar to other reported cases of
      oral cartilaginous choristomas.

PMID- 25574732
TI  - Atypical presentation of salivary mucocele: diagnosis and management.
AB  - A mucocele is a common pathological lesion involving the minor salivary glands.
      It usually presents as an asymptomatic small superficial swelling over the lower
      labial mucosa. However, uncommon variants of oral mucoceles sometimes occur. Such
      lesions may be difficult to diagnose due to their unusual size and atypical
      clinical presentation. This article describes the case of a deeply embedded large
      mucocele over the buccal mucosa. Ultrasonography was used to visualize the size
      and position of the lesion, and aspiration was used to help in the eventual
      diagnosis. An intraoral approach was used in the complete removal of the lesion. 

PMID- 25574733
TI  - A large dentigerous cyst treated with decompression and orthosurgical traction: a
      case report.
AB  - This article presents the case of an 8-year-old patient who presented with a
      large radiolucency associated with the maxillary left canine and a supernumerary
      tooth. A computed tomography scan showed the radiolucency was in close proximity
      to the roots of the anterior teeth, with no areas of root resorption, and
      expansion into the left maxillary sinus. The boundaries of the maxillary sinus
      floor were still preserved. After positive aspiration of intralesional liquid and
      due to the large size of the radiolucency, a decompression technique was selected
      to preserve the permanent canine. Surgery was performed to remove the
      supernumerary tooth, followed by orthodontic treatment and surgery to allow
      access for orthodontic traction of the permanent canine. More than 5 years post
      treatment, no recurrence was observed and the therapeutic option to position and
      preserve the permanent canine was successful. 

PMID- 25574734
TI  - Impact of toothbrushing with a dentifrice containing calcium peroxide on enamel
      color and roughness.
AB  - This in vitro study sought to evaluate both the bleaching potential and changes
      to average surface roughness (Ra) of enamel after brushing with a dentifrice.
      Fifty-four enamel specimens (4 x 4 x 2 mm) were divided into 3 groups (n = 18)
      and treated with 1 of 3 dentifrices: 1 with calcium peroxide, and 2 without. The
      samples were submitted to 20,000 brushing cycles. Color and Ra were measured
      before and after brushing. Although the Ra increased in all groups after
      brushing, only the dentifrice containing calcium peroxide resulted in an increase
      in reflectance.

PMID- 25574735
TI  - Synthesis of enantiopure reversed structured ether lipids of the 1-O-alkyl-sn-2,3
      diacylglycerol type.
AB  - This report describes the synthesis of reversed structured 1-O-alkyl-2,3-diacyl
      sn-glycerols (DAGEs) possessing a pure saturated even number fatty acid (C6:0
      C16:0) at the sn-2 position along with a pure EPA or DHA located at the terminal
      sn-3 position of the glycerol backbone of chimyl, batyl and selachyl alcohols.
      These adducts were synthesized by a highly efficient two-step chemoenzymatic
      process involving an immobilized Candida antarctica lipase to introduce pure EPA
      and DHA activated as oxime esters exclusively to the sn-3 terminal position of
      enantiopure chimyl, batyl and selachyl alcohols in excellent yields. The
      saturated fatty acids were subsequently incorporated to the remaining sn-2
      position of the resulting 3-monoacylglyceryl ethers (3-MAGEs) using EDAC coupling
      agent in the presence of DMAP in very high to excellent yields (85%-98%). No
      losses of enantiomeric composition were observed during these processes. The
      multiple utilities of the resulting focused library of reversed structured DAGEs
      are discussed including how such compounds may possibly be utilized within the
      pharmaceutical area. 

PMID- 25574737
TI  - Chitosan in mucoadhesive drug delivery: focus on local vaginal therapy.
AB  - Mucoadhesive drug therapy destined for localized drug treatment is gaining
      increasing importance in today's drug development. Chitosan, due to its known
      biodegradability, bioadhesiveness and excellent safety profile offers means to
      improve mucosal drug therapy. We have used chitosan as mucoadhesive polymer to
      develop liposomes able to ensure prolonged residence time at vaginal site. Two
      types of mucoadhesive liposomes, namely the chitosan-coated liposomes and
      chitosan-containing liposomes, where chitosan is both embedded and surface
      available, were made of soy phosphatidylcholine with entrapped fluorescence
      markers of two molecular weights, FITC-dextran 4000 and 20,000, respectively.
      Both liposomal types were characterized for their size distribution, zeta
      potential, entrapment efficiency and the in vitro release profile, and compared
      to plain liposomes. The proof of chitosan being both surface-available as well as
      embedded into the liposomes in the chitosan-containing liposomes was found. The
      capability of the surface-available chitosan to interact with the model porcine
      mucin was confirmed for both chitosan-containing and chitosan-coated liposomes
      implying potential mucoadhesive behavior. Chitosan-containing liposomes were
      shown to be superior in respect to the simplicity of preparation, FITC-dextran
      load, mucoadhesiveness and in vitro release and are expected to ensure prolonged
      residence time on the vaginal mucosa providing localized sustained release of
      entrapped model substances. 

PMID- 25574736
TI  - Statistical research on the bioactivity of new marine natural products discovered
      during the 28 years from 1985 to 2012.
AB  - Every year, hundreds of new compounds are discovered from the metabolites of
      marine organisms. Finding new and useful compounds is one of the crucial drivers
      for this field of research. Here we describe the statistics of bioactive
      compounds discovered from marine organisms from 1985 to 2012. This work is based
      on our database, which contains information on more than 15,000 chemical
      substances including 4196 bioactive marine natural products. We performed a
      comprehensive statistical analysis to understand the characteristics of the novel
      bioactive compounds and detail temporal trends, chemical structures, species
      distribution, and research progress. We hope this meta-analysis will provide
      useful information for research into the bioactivity of marine natural products
      and drug development. 

PMID- 25574738
TI  - New meroterpenoids from the endophytic fungus Aspergillus flavipes AIL8 derived
      from the mangrove plant Acanthus ilicifolius.
AB  - Four new meroterpenoids (2-5), along with three known analogues (1, 6, and 7)
      were isolated from mangrove plant Acanthus ilicifolius derived endophytic fungus
      Aspergillus flavipes. The structures of these compounds were elucidated by NMR
      and MS analysis, the configurations were assigned by CD data, and the
      stereochemistry of 1 was confirmed by X-ray crystallography analysis. A possible
      biogenetic pathway of compounds 1-7 was also proposed. All compounds were
      evaluated for antibacterial and cytotoxic activities. 

PMID- 25574739
TI  - LC-MS-based metabolomics study of marine bacterial secondary metabolite and
      antibiotic production in Salinispora arenicola.
AB  - An LC-MS-based metabolomics approach was used to characterise the variation in
      secondary metabolite production due to changes in the salt content of the growth
      media as well as across different growth periods (incubation times). We used
      metabolomics as a tool to investigate the production of rifamycins (antibiotics)
      and other secondary metabolites in the obligate marine actinobacterial species
      Salinispora arenicola, isolated from Great Barrier Reef (GBR) sponges, at two
      defined salt concentrations and over three different incubation periods. The
      results indicated that a 14 day incubation period is optimal for the maximum
      production of rifamycin B, whereas rifamycin S and W achieve their maximum
      concentration at 29 days. A "chemical profile" link between the days of
      incubation and the salt concentration of the growth medium was shown to exist and
      reliably represents a critical point for selection of growth medium and harvest
      time. 

PMID- 25574740
TI  - Penicibrocazines A-E, five new sulfide diketopiperazines from the marine-derived
      endophytic fungus Penicillium brocae.
AB  - Five new sulfide diketopiperazine derivatives, namely, penicibrocazines A-E (1
      5), along with a known congener (6), were isolated and identified from the
      culture extract of Penicillium brocae MA-231, an endophytic fungus obtained from
      the fresh tissue of the marine mangrove plant Avicennia marina. The structures of
      these compounds were elucidated by detailed interpretation of NMR and mass
      spectroscopic data and the structures of compounds 1 and 3 were confirmed by
      single-crystal X-ray diffraction analysis. All these compounds were examined for
      cytotoxic and antimicrobial activities. Compounds 2-6 exhibited antimicrobial
      activity against some of the tested strains with MIC values ranging from 0.25 to
      64 MUg/mL. 

PMID- 25574742
TI  - Impairment of glutamine/glutamate-gamma-aminobutyric acid cycle in manganese
      toxicity in the central nervous system.
AB  - Manganese (Mn) is an essential trace element that is required for maintaining the
      proper function and regulation of many biochemical and cellular reactions.
      Despite its essentiality, at excessive levels Mn is toxic to the central nervous
      system. The overdose accumulation of Mn in specific brain areas, such as the
      substantia nigra, the globus pallidus and the striatum, triggers neurotoxicity
      resulting in a neurological brain disorder, referred to as manganism. Manganese
      toxicity is associated with the disruption of glutamine (Gln)/glutamate (Glu)
      GABA cycle (GGC). The GGC represents a complex process, since Gln efflux from
      astrocytes must be met by its influx in neurons. Mn toxicity is associated with
      the disruption of both of these critical points in the cycle. In cultured
      astrocytes, pre-treatment with Mn inhibits the initial net uptake of Gln in a
      concentration-dependent manner. Manganese added directly to astrocytes induces
      deregulation in the expression of SNAT3, SNAT2, ASCT2 and LAT2 transporters and
      significantly decreases in Gln uptake mediated by the transporting Systems N and
      ASC, and a decrease in Gln efflux mediated by Systems N, ASC and L. Further, Mn
      disrupts Glu transporting systems leading to both a reduction in Glu uptake and
      elevation in extracellular Glu levels. Interestingly, there appear to be common
      signaling targets of Mn in GGC cycling in glial cells. Namely, the PKC signaling
      is affected by Mn in Gln and Glu transporters expression and function.
      Additionally, Mn was identified to deregulate glutamine synthetase (GS)
      expression and activity. Those evidences could triggers depletion of Gln
      synthesis/metabolism in glia cells and consequently diminish astrocytic-derived
      glutamine, while disruption of Glu removal/transport can mediate dyshomeostasis
      in neurotransmission of functioning neurons. Overdose and excessive Mn
      accumulations in astrocytes not only culminate in pathology, but also affect
      astrocytic protective properties and defect or alternate astrocyte-neuronal
      integrity. Here we highlight the mechanistic commonalities inherent to Mn
      neurotoxicity related to the astrocyte pathology and GGC impairment. 

PMID- 25574743
TI  - In vitro pharmacological evaluation of the radiolabeled C-terminal substance P
      analogue Lys-Phe-Phe-Gly-Leu-Met-NH2: Does a specific binding site exist?
AB  - In the present paper, we report the synthesis, radiolabeling and comprehensive
      pharmacological evaluation of a C-terminally truncated tachykinin derivative, 3H
      KFFGLM-NH2. The C-terminal fragments of endogenous tachykinins are pharmacophores
      responsible for interaction with the tachykinin receptors NK1, NK2 and NK3. The N
      terminal fragments are responsible for modulation of receptor selectivity and
      interactions with other receptor systems. To evaluate and separate the function
      of an NK-pharmacophore from the activity of its parent neurokinin, KFFGLM-NH2 was
      synthesized in both tritiated and unlabeled forms. It has been proposed that the
      obtained NK-binding profiles of specific reference ligands and KFFGLM-NH2
      differentiate monomeric and dimeric forms of NK receptors. We hypothesize that
      dimers of NK receptors could be specific receptor(s) for C-terminal fragments of
      all neurokinins as well as their C-terminal fragments, including H-KFFGLM-NH2.
      Dissociation of dimers into monomers opens access to additional allosteric
      binding sites. Fully elongated undecapeptide substance P interacts with both the
      "tachykinin pocket" and the "allosteric pocket" on the monomeric NK1 receptor,
      resulting in high and selective activation. However, C-terminal hexapeptide
      fragment analogues, recognizing only the "tachykinin pocket", may have less
      specific interactions with all tachykinin receptors in both monomeric and dimeric
      forms. 

PMID- 25574741
TI  - Limited genomic heterogeneity of circulating melanoma cells in advanced stage
      patients.
AB  - Purpose. Circulating melanoma cells (CMCs) constitute a potentially important
      representation of time-resolved tumor biology in patients. To date, genomic
      characterization of CMCs has been limited due to the lack of a robust methodology
      capable of identifying them in a format suitable for downstream characterization.
      Here, we have developed a methodology to detect intact CMCs that enables
      phenotypic, morphometric and genomic analysis at the single cell level.
      Experimental design. Blood samples from 40 metastatic melanoma patients and 10
      normal blood donors were prospectively collected. A panel of 7 chondroitin
      sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAbs) was used to
      immunocytochemically label CMCs. Detection was performed by automated digital
      fluorescence microscopy and multi-parametric computational analysis. Individual
      CMCs were captured by micromanipulation for whole genome amplification and copy
      number variation (CNV) analysis. Results. Based on CSPG4 expression and nuclear
      size, 1-250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients
      (0.5-371.5 CMCs ml(-1)). Morphometric analysis revealed that CMCs have a broad
      spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear
      size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV
      analysis of single CMCs identified deletions of CDKN2A and PTEN, and
      amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal
      amplifications in chr12, 17 and 19 were also found. Conclusions. Our findings
      show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma
      patients. High content analysis of this cell population may contribute to the
      design of effective personalized therapies in patients with melanoma. 

PMID- 25574744
TI  - Assessment of antioxidative activity of alkaloids from Huperzia selago and
      Diphasiastrum complanatum using in vitro systems.
AB  - Free radical-induced oxidative damage is implicated in the pathogenesis of
      neurodegenerative disorders, and antioxidants are presumably of therapeutic value
      in such diseases. Our previous data indicated that free radicals are strongly
      associated with brain aging and also play an important role in cytotoxicity of
      amyloidogenic proteins including ?-synuclein and amyloid ?, which accumulate in
      brains during Parkinson's and Alzheimer's diseases. Disruption of the equilibrium
      of pro-oxidants and antioxidants results in oxidative stress that leads to the
      modification of DNA, proteins, carbohydrates, and lipids. It is widely accepted
      that antioxidants acting as radical scavengers protect the brain against
      oxidative damage in neurodegenerative diseases. Plant products are rich sources
      of phytochemicals and have been found to possess a variety of biological
      activities, including antioxidative potential. The aim of this study was to
      analyse the antioxidative potential of alkaloid fractions from Huperzia selago
      and Diphasiastrum complanatum to protect macromolecules against oxidative damage.
      Thin layer chromatography (TLC) and high-performance liquid chromatography with
      diode array (HPLC-DAD) and electrospray ionisation mass spectrometric detection
      (ESI-MS/MS) were used to carry out a comprehensive characterization of alkaloids
      isolated from the plant material. The effect of the tested compounds on
      iron/ascorbate-induced lipid peroxidation and carbonyl group formation was
      analysed in the rat brain homogenate. Direct free radical scavenging (DPPH assay)
      and the effect on dityrosine formation were measured in cell-free systems. Our
      results indicated that a number of alkaloid extracts at concentration of 25 ug/ml
      exhibited antioxidant activity as indicated by DPPH radical scavenging potential
      (up to 59% inhibition) and inhibition of dityrosine formation. Selected alkaloid
      fractions provided significant protection against lipid peroxidation and protein
      oxidation in rat brain tissue homogenate, reducing iron/ascorbate-induced damage
      by about 20% and 76%, respectively. Overall, the results indicated that selected
      alkaloids isolated from Huperzia selago effectively protect macromolecules from
      oxidative stress injury, which will give us an insight into the potential of
      alkaloids in terms of opening up a new therapeutic approach for oxidative stress
      dependent disorders. 

PMID- 25574745
TI  - Non-woven nanofiber mats - a new perspective for experimental studies of the
      central nervous system?
AB  - (Sub)chronic local drug application is clearly superior to systemic
      administration, but may be associated with substantial obstacles, particularly
      regarding the applications to highly sensitive central nervous system (CNS)
      structures that are shielded from the outer environment by the blood-brain
      barrier. Violation of the integrity of the barrier and CNS tissues by a
      permanently implanted probe or cannula meant for prolonged administration of
      drugs into specific CNS structures can be a severe confounding factor because of
      the resulting inflammatory reactions. In this study, we tested the utility of a
      novel way for (sub)chronic local delivery of highly active (i.e., used in very
      low amounts) drugs to the rat spinal cord employing a non-woven nanofiber mat
      dressing. To this end, we compared the morphology and motoneuron (? + ?) counts
      in spinal cord cervical and lumbar segments between rats with glutamate-loaded
      nanofiber mats applied to the lumbar enlargement and rats with analogical
      implants carrying no glutamate. Half of the rats with glutamate-loaded implants
      were given daily valproate treatment to test its potential for counteracting the
      detrimental effects of glutamate excess. The mats were prepared in-house by
      electrospinning of an emulsion made of a solution of the biocompatible and
      biodegradable poly(L-lactide-co-caprolactone) polymer in a mixture of organic
      solvents, an aqueous phase with or without monosodium glutamate, and sodium
      dodecyl sulfate as an emulsifier; the final glutamate content was 1.4 ug/mg of
      the mat. Three weeks after mat implantation there was no inflammation or
      considerable damage of the spinal cord motoneuron population in the rats with the
      subarachnoid dressing of a glutamate-free mat, whereas the spinal cords of the
      rats with glutamate-loaded nanofiber mats showed clear symptoms of excitotoxic
      damage and a substantial increase in dying/damaged motoneuron numbers in both
      segments studied. The rats given systemic valproate treatment showed
      significantly lower percentages of damaged/dying motoneurons in their lumbar
      enlargements. These results demonstrate the capacity of nanofiber mats for
      generation of neurotoxic glutamate in the rat CNS. However, the tested nanofiber
      mats need further improvements aimed at extending the period of effective drug
      release and rendering the release more steady. 

PMID- 25574746
TI  - On the lack of a clear-cut association between alpha-2-macroglobulin deletion and
      the risk of Alzheimer disease in Poland.
AB  - Alzheimer disease (AD) is a complex, multi-factorial disease with the potential
      involvement of several genes. Alpha-2- macroglobulin (A2M) has been implicated in
      AD on the basis of its ability to mediate the clearance and degradation of ?
      amyloid peptide. Nevertheless, it is not clear whether there are racial
      differences in frequency of polymorphisms of A2M in AD. We examined a group of 50
      unrelated patients from Poland (38 women and 12 men), who were diagnosed
      clinically as probably developing AD (according to the N1NCD3 - ADR PA criteria).
      The patients were examined by a neurologist and a psychologist and had a CT or
      MRI scan of the brain. Fifty individuals of matched age, without any signs of
      dementia, were studied as a control group. DNA was extracted by a routine method
      from a blood sample. Amplification and genotyping at A2M was performed as
      described by Blacker et al. (1997). The genotypic distribution in A2M exon 18 in
      patients with AD and genotype TT in A2M exon 24 was similar to that in the
      controls. Significant differences were noted only in early onset AD in males and
      for old onset disease in females. The deletions were found more frequently in AD;
      however, they were found in only a small proportion of studied patients. These
      findings indicate that A2M is not the only biological candidate gene for AD
      determination. 

PMID- 25574747
TI  - Prevalence of small cerebral bleeds in patients with progressive supranuclear
      palsy: a neuropathological study with 7.0-Tesla magnetic resonance imaging
      correlates.
AB  - INTRODUCTION: Progressive supranuclear palsy (PSP) is a degenerative disease
      affecting mainly the brain stem, basal ganglia and cerebellum. Associated
      cerebrovascular lesions, mainly small cerebral bleeds, are frequently observed in
      some neurodegenerative diseases such as Alzheimer dementia and rare in others
      such as frontotemporal lobar degeneration. The present post-mortem study
      investigates the prevalence and distribution of small cerebral bleeds in PSP
      brains. MATERIAL AND METHODS: Nineteen brains of PSP patients were compared to 12
      age-matched controls. The prevalence and distribution of mini-bleeds were
      investigated on a coronal section of a cerebral hemisphere at the level of the
      mamillary bodies and on a horizontal section through the pons and cerebellum. In
      addition, out of these series T2*-weighted gradient-echo 7.0-Tesla magnetic
      resonance imaging (MRI) of 3 coronal sections of a cerebral hemisphere and of a
      brain stem and cerebellum was performed in 14 PSP and 11 control brains. RESULTS:
      Although the total number of mini-bleeds was the same on neuropathological
      examination of both groups, they prevailed around the dentate nucleus of the
      cerebellum (p = 0.05) and in the tegmentum pontis (p = 0.05) of the PSP brains.
      On MRI the small bleeds were also more frequent around the dentate nucleus of the
      cerebellum (p = 0.02) and in the pons (p = 0.04) of PSP brains. DISCUSSION: In
      PSP brains, mini-bleeds only prevail in the regions affected by the
      neurodegenerative process, similarly to what happens in frontotemporal lobar
      degeneration. They should be considered as the result of increased angiogenesis
      and microglial activation, leading to associated disturbances of the blood-brain
      barrier in the most affected regions of PSP. They are not indicative of
      cerebrovascular disease.

PMID- 25574748
TI  - Methyl-CpG binding protein 2, receptors of innate immunity and receptor for
      advanced glycation end-products in human viral meningoencephalitis.
AB  - Inflammation is a normal host defense reaction to infections and tissue injury.
      In pathology, the process of inflammation is deregulated by various environmental
      factors, prolonged activation of Toll-like receptors (TLRs), induction of
      epigenetic machinery or expression of receptors for advanced glycation end
      products (RAGE). In the present study, we examined immunoexpression of proteins
      participating in the above-mentioned mechanisms, in the brain of patients with
      viral meningoencephalitis. The results showed that depending on the period of the
      disease, the process of inflammation is deregulated in different ways. In an
      early period of viral meningoencephalitis, we found numerous so-called microglial
      nodules which were strongly immunopositive to methyl-CpG protein 2 (MeCP2). This
      protein is an epigenetic factor important for methylation of DNA; therefore, our
      results suggest that cells collected in the nodules may participate in
      modification of the host defense reaction. Moreover, in the early period of viral
      meningoencephalitis, we found that Purkinje cells of the cerebellum contain TLR3
      or TLR9 receptors that can recognize viral pathogens and may activate a self
      destructive mechanism in these neurons. In the later (advanced) period of viral
      meningoencephalitis, despite some of the above observations, RAGE protein was
      detected in the brain of adult and aging patients. It means that in this period
      of the disease, the inflammatory process may be deregulated by numerous post
      translationally modified proteins that are transported to the brain after binding
      with activated RAGE. In addition, young patients appeared more susceptible to
      viral infections than adult and aging patients, because most of them died during
      the early period of meningoencephalitis. 

PMID- 25574749
TI  - Mitofusin 2 expression dominates over mitofusin 1 exclusively in mouse dorsal
      root ganglia - a possible explanation for peripheral nervous system involvement
      in Charcot-Marie-Tooth 2A.
AB  - Mitofusin 2 (Mfn2), a protein of the mitochondrial outer membrane, is essential
      for mitochondrial fusion and contributes to the maintenance and operation of the
      mitochondrial network. Mutations in the mitofusin 2 gene cause axonal Charcot
      Marie-Tooth type 2A (CMT2A), an inherited disease affecting peripheral nerve
      axons. The precise mechanism by which mutations in MFN2 selectively cause the
      degeneration of long peripheral axons is not known. There is a hypothesis
      suggesting the involvement of reduced expression of a homologous protein,
      mitofusin 1 (Mfn1), in the peripheral nervous system, and less effective
      compensation of defective mitofusin 2 by mitofusin 1. We therefore aimed to
      perform an analysis of the mitofusin 1 and mitofusin 2 mRNA and protein
      expression profiles in different mouse tissues, with special attention paid to
      dorsal root ganglia (DRGs), as parts of the peripheral nervous system.
      Quantitative measurement relating to mRNA revealed that expression of the Mfn2
      gene dominates over Mfn1 mainly in mouse DRG, as opposed to other nervous system
      samples and other tissues studied. This result was further supported by Western
      blot evaluation. Both these sets of data confirm the hypothesis that the cellular
      consequences of mutations in the mitofusin 2 gene can mostly be manifested in the
      peripheral nervous system. 

PMID- 25574750
TI  - Blood vessel ultrastructural picture in a CADASIL patient diagnosed at an
      advanced age.
AB  - We report the case of an 84-year-old male patient afflicted by cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
      showing minimal symptoms of disease. The patient was diagnosed on the basis of
      ultrastructural and genetic examinations. Ultrastructurally, a typical vascular
      pathology was found. However, in abnormal capillary vessel walls no granular
      osmiophilic material (GOM) was found. In the arteriole there were only a few GOM
      deposits that revealed various structures, of which only some resembled typical
      round GOM. The arteriolar walls showed severe damage, including fragmentation,
      degeneration and loss of vascular smooth muscle cells (VSMCs) with numerous
      deposits of elastin, mucosubstances, different granular debris, as well as
      collagen fibres in the basement membrane. Lysosomal inclusions with fingerprint
      morphology, atypical for CADASIL, were located in some of the VSMCs. Very old age
      at the onset of the disease may suggest that morphological changes in blood
      vessels, described in this report, may be due to both the disease and the
      patient's age. To our best knowledge it is the first description of pathology of
      blood vessels and GOM morphology in a CADASIL patient diagnosed at an advanced
      age. 

PMID- 25574751
TI  - Case report of an adolescent girl with limb-girdle muscular dystrophy type 2B -
      the usefulness of muscle protein immunostaining in the diagnosis of
      dysferlinopathies.
AB  - Dysferlinopathies are rare disorders of muscle that present two main phenotypes:
      Miyoshi myopathy with primarily distal weakness and limb-girdle muscular
      dystrophy type 2B (LGMD2B) with primarily proximal weakness. They are caused by
      mutations in the gene encoding the skeletal muscle protein dysferlin, which is
      involved in muscle repair. The clinical presentation of the disease is rather
      uncharacteristic, and molecular genetic testing is long-lasting; thus muscle
      biopsy may be essential in the diagnostic process. Histology itself reveals non
      specific changes, but a variety of currently available muscle protein
      immunostains may be very helpful. We present a 19-year-old girl with epilepsy and
      elevated creatine phosphokinase (CPK) concentration. Due to increased CPK,
      myopathy was suspected and muscle biopsy was performed. Light microscopy showed
      no distinctive myopathic changes, and electron microscopy showed no
      abnormalities. Extended immunohistochemistry, performed much later, showed
      complete absence of dysferlin immunostaining. Based on that result, the diagnosis
      of LGMD2B was made, with subsequent genetic testing to be done. Two known
      pathogenic variants were found in the DYSF gene, confirming the diagnosis of
      LGMD2B and allowing proper genetic counseling. 

PMID- 25574752
TI  - Frontotemporal lobar degeneration with MAPT mutation in an Italian-Polish family.
      A case report.
AB  - Frontotemporal lobar degeneration (FTLD) with mutations in the MAPT (microtubule
      associated protein tau) gene (FTLD with MAPT mutation) is a neurodegenerative
      disease with various clinical phenotypes. We present an Italian- Polish family
      with a IVS10+3G>A mutation in the MAPT gene, linked with haplotype H1s in a male
      proband (Fig. 2, II.2, H1s/H1b diplotype) and his sister (Fig. 2, II.1, the
      H1s/H1j diplotype). This report presents clinical, neuropathological and genetic
      testing of the proband and his affected sister, two members of an Italian-Polish
      family consisting of 25 family members. Their clinical history includes dementia
      as well as movement and cardiovascular disorders. Magnetic resonance imaging
      showed frontal and temporal cerebral atrophy. Neuropathological studies of the
      brain samples showed loss of neurons, gliosis, and the occurrence of
      neurofibrillary tangles, numerous neuropil threads, coiled bodies and abundant
      deposits of tau protein, including 3- and 4-repeated isoforms in neurons and
      glial cells. Only in the male proband brain, there were Pick body-like deposits
      in granule neurons of the hippocampus. Pathology of vascular walls was found in
      both cases. Ultrastructurally, the male proband showed clusters of collagen
      fibers mainly in a pericyte position. Beside the typical neurofibrillary
      pathology, aggregated gliofilaments and lipofuscin deposits in astroglia are
      described. Our report suggests that FTLD with IVS10+3G>A MAPT mutation causes
      damage mainly to the central nervous system and induces neuropathological
      changes, depending on the haplotypes of MAPT. In the clinical course of this
      disease, damage of the cardiovascular system may also be observed. 

PMID- 25574755
TI  - A simplified edge illumination set-up for quantitative phase contrast mammography
      with synchrotron radiation at clinical doses.
AB  - This work presents the first study of x-ray phase contrast imaging based on a
      simple implementation of the edge illumination method (EIXPCi) in the field of
      mammography with synchrotron radiation. A simplified EIXPCi set-up was utilized
      to study a possible application in mammography at clinical doses. Moreover,
      through a novel algorithm capable of separating and quantifying absorption and
      phase perturbations of images acquired in EIXPCi modality, it is possible to
      extract quantitative information on breast images, allowing an accurate tissue
      identification. The study was carried out at the SYRMEP beamline of Elettra
      synchrotron radiation facility (Trieste, Italy), where a mastectomy specimen was
      investigated with the EIXPCi technique. The sample was exposed at three different
      energies suitable for mammography with synchrotron radiation in order to test the
      validity of the novel algorithm in extracting values of linear attenuation
      coefficients integrated over the sample thickness. It is demonstrated that the
      quantitative data are in good agreement with the theoretical values of linear
      attenuation coefficients calculated on the hypothesis of the breast with a given
      composition. The results are promising and encourage the current efforts to apply
      the method in mammography with synchrotron radiation. 

PMID- 25574753
TI  - The Status of Heligmosomoides americanus, Representative of an American Clade of
      Vole-Infecting Nematodes.
AB  - Heligmosomoides americanus is shown by molecular phylogenetic analysis of 3
      nuclear (28S, ITS1, and ITS2) and 2 mitochondrial (cytochrome oxidase 1 and
      cytochrome b) loci to be a distinct species of heligmosomid nematode with a long
      independent evolutionary history, and not a subspecies of Heligmosomoides
      polygyrus . Rather than being a recent arrival in North America, the species
      probably originated as a Beringian immigrant with the host vole Phenacomys,
      approximately 2 million years ago (MYA). 

PMID- 25574754
TI  - Hematopoietic stem cell enhancer: a powerful tool in stem cell biology.
AB  - There has been considerable interest in identifying a cis-regulatory element that
      targets gene expression to stem cells. Such an element, termed stem cell
      enhancer, holds the promise of providing important insights into the
      transcriptional programs responsible for inherent stem cell-specific properties
      such as self-renewal capacity. The element also serves as a molecular handle for
      stem cell-specific marking, transgenesis and gene targeting, thereby becoming
      invaluable to stem cell research. A series of candidate enhancers have been
      identified for hematopoietic stem cells (HSCs). This review summarizes currently
      known HSC enhancers with emphasis on an intronic enhancer in the Runx1 gene which
      is essential for the generation and maintenance of HSCs. The element, named eR1
      (+24m), is active specifically in HSCs, but not in progenitors, and is hence the
      most definitive HSC enhancer. 

PMID- 25574756
TI  - High-spin organic molecules.
AB  - Organic molecules with high-spin ground states, besides being fundamentally
      interesting, possess numerous potential applications in diverse fields such
      organic magnetism, MRI contrast agents, and spintronics. Such molecules, once
      thought to exist only as highly reactive intermediates, can be rationally
      designed to have adequate stability for organic synthesis and characterization.
      This Synopsis provides an overview of the factors that lead to high-spin ground
      states as well as recent progress in the design and synthesis of high-spin
      organic molecules. 

PMID- 25574757
TI  - Marked difference in self-assembly, morphology, and cell viability of positional
      isomeric dipeptides generated by reversal of sequence.
AB  - In this study two positional isomeric dipeptides Boc-m-ABA-Aib-OMe () and Boc-Aib
      m-ABA-OMe () synthesized by reversal of the positions of two rigid amino acids (m
      ABA: m-aminobenzoic acid, Aib: alpha-aminoisobutyric acid) showed marked
      difference in morphology under the same environmental conditions. Investigation
      of single crystal structures reveals the difference in crystal packing and higher
      order self-assembly pattern for both the isomeric peptides, which might be the
      responsible factor for their different morphological patterns. Moreover, these
      isomeric dipeptides have produced different cellular viability effects towards
      normal bone cells. These two peptides would have utilities in the model study of
      isomeric peptides/proteins, where morphological difference under identical
      conditions brings changes in their individual bio-activities and where the
      reversal of sequence causes different cellular viability and generates health
      hazard. 

PMID- 25574758
TI  - A magnetically highly frustrated Cu(II)27 coordination cluster containing a Cu18
      folded-sheet motif.
AB  - [Cu(II)27(MU4-O)2(OH)13(OMe)7(vanox)10(NO3)8(OH2)2(MeOH)7](NO3)2.2H2O.11MeOH (1)
      was synthesised from Cu(NO3)2.3H2O and o-vanillin-oxime. Structural analysis
      shows a molecule composed of a Cu18 "folded-sheet" motif linked to a Cu9 bridging
      unit. The cluster is highly frustrated and has an S = 1/2 spin ground state.

PMID- 25574759
TI  - Achieving the photon up-conversion thermodynamic yield upper limit by sensitized
      triplet-triplet annihilation.
AB  - Triplet-triplet annihilation (TTA) based up-conversion is a promising strategy
      for light harvesting the low-energy tail of the solar spectrum with photovoltaic
      technologies. Here, we present a bi-component system for photon managing via TTA
      that allows bypassing the classical statistic limit of 2/5 in the singlet
      generation, achieving a near unitary conversion efficiency. This result is
      obtained because of the peculiar relative position of the triplet and singlet
      energy levels of perylene, used as up-converter and emitter. The system shows a
      record red-to-blue external up-conversion yield of ~10% under an irradiance of 1
      sun. 

PMID- 25574760
TI  - A review: microRNA detection methods.
AB  - MicroRNA (miRNA) detection is of considerable significance in both disease
      diagnosis and in the study of miRNA function. The importance of miRNA itself is
      due to the complicated regulatory functions it plays in various life processes
      and its close relationship with some diseases. Traditional methods for miRNA
      detection do not meet the current demands, so various novel methods have been
      developed with a special focus on sensitivity and specificity. Herein, we
      summarize and discuss the newly developed miRNA detection methods. 

PMID- 25574761
TI  - Bi-compartmental responsive polymer particles.
AB  - A novel type of bi-compartmental copolymer particle was synthesized in one-pot by
      controlling the phase separation during the polymerization process. The resulting
      particles have two distinct compartments, one consisting of mainly poly(acrylic
      acid) (PAA) and the other of poly(N,N'-isopropylacrylamide) (PNIPAM). The
      particles exhibit changeable shapes and properties, such as swelling in solvents
      and deposition on surfaces, and can be used to control emulsification as a
      function of pH. 

PMID- 25574762
TI  - Interaction of Sorghum Tannins with Wheat Proteins and Effect on in Vitro Starch
      and Protein Digestibility in a Baked Product Matrix.
AB  - Carbohydrates contribute the most dietary calories, which makes starchy foods a
      logical target for modifying calorie intake. This study investigated the
      interaction of sorghum bran proanthocyanidins (PA) with proteins during wheat
      flour tortilla processing and impact on in vitro starch digestibility. Brans from
      wheat, white (low in phenols), brown (high PA), and black (high monomeric
      flavonoids) sorghum were used. Changes in phenolic profile, starch, and proteins
      were evaluated. Dough mixing drastically decreased extractable PA (61-72%) but
      not monomeric phenolics; higher MW PA decreased the most. The high PA bran dough
      produced the highest insoluble proteins (460 vs 330 mg/g protein for other
      sorghum brans) at 25% baker's substitution. The high PA bran tortillas also had
      higher slow digesting starch and lower rapidly digesting starch than all other
      bran treatments. Significant sorghum PA-gluten interactions occur during dough
      mixing that may slow starch digestibility in the baked products.

PMID- 25574763
TI  - Facile synthesis and lithium storage properties of a porous NiSi2/Si/carbon
      composite anode material for lithium-ion batteries.
AB  - In this work, a novel, porous structured NiSi2/Si composite material with a core
      shell morphology was successfully prepared using a facile ball-milling method.
      Furthermore, the chemical vapor deposition (CVD) method is deployed to coat the
      NiSi2/Si phase with a thin carbon layer to further enhance the surface electronic
      conductivity and to mechanically stabilize the whole composite structure. The
      morphology and porosity of the composite material was evaluated by scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen
      adsorption measurements (BJH analysis). The as-prepared composite material
      consists of NiSi2, silicon, and carbon phases, in which the NiSi2 phase is
      embedded in a silicon matrix having homogeneously distributed pores, while the
      surface of this composite is coated with a carbon layer. The electrochemical
      characterization shows that the porous and core-shell structure of the composite
      anode material can effectively absorb and buffer the immense volume changes of
      silicon during the lithiation/delithiation process. The obtained NiSi2/Si/carbon
      composite anode material displays an outstanding electrochemical performance,
      which gives a stable capacity of 1272 mAh g(-1) for 200 cycles at a
      charge/discharge rate of 1C and a good rate capability with a reversible capacity
      of 740 mAh g(-1) at a rate of 5C. 

PMID- 25574765
TI  - Characterization of fine motor development: dynamic analysis of children's
      drawing movements.
AB  - In this study, we investigated children's fine motor development by analyzing
      drawing trajectories, kinematics and kinetics. Straight lines drawing task and
      circles drawing task were performed by using a force sensitive tablet. Forty
      right-handed and Chinese mother-tongue students aged 6-12, attending classes from
      grade 1 to 5, were engaged in the experiment. Three spatial parameters, namely
      cumulative trace length, vector length of straight line and vertical diameter of
      circle were determined. Drawing duration, mean drawing velocity, and number of
      peaks in stroke velocity profile (NPV) were derived as kinematic parameters.
      Besides mean normal force, two kinetic indices were proposed: normalized force
      angle regulation (NFR) and variation of fine motor control (VFC) for circles
      drawing task. The maturation and automation of fine motor ability were reflected
      by increased drawing velocity, reduced drawing duration, NPV and NFR, with
      decreased VFC in circles drawing task. Grade and task main effects as well as
      significant correlations between age and parameters suggest that factors such as
      schooling, age and task should be considered in the assessment of fine motor
      skills. Compared with kinematic parameters, findings of NFR and VFC revealed that
      kinetics is another important perspective in the analysis of fine motor movement.

PMID- 25574764
TI  - Antibacterial drug leads: DNA and enzyme multitargeting.
AB  - We report the results of an investigation of the activity of a series of amidine
      and bisamidine compounds against Staphylococcus aureus and Escherichia coli. The
      most active compounds bound to an AT-rich DNA dodecamer (CGCGAATTCGCG)2 and using
      DSC were found to increase the melting transition by up to 24  degrees C. Several
      compounds also inhibited undecaprenyl diphosphate synthase (UPPS) with IC50
      values of 100-500 nM, and we found good correlations (R(2) = 0.89, S. aureus;
      R(2) = 0.79, E. coli) between experimental and predicted cell growth inhibition
      by using DNA DeltaTm and UPPS IC50 experimental results together with one
      computed descriptor. We also solved the structures of three bisamidines binding
      to DNA as well as three UPPS structures. Overall, the results are of general
      interest in the context of the development of resistance-resistant antibiotics
      that involve multitargeting. 

PMID- 25574766
TI  - Ligand-based modeling followed by in vitro bioassay yielded new potent
      glucokinase activators.
AB  - Glucokinase (GK) has received recent interest as a valid antidiabetic target.
      With this in mind, we applied a computational workflow based on combining
      pharmacophore modeling and QSAR analysis followed by in silico screening toward
      the discovery of novel GK activators. Virtual screening identified 10 promising
      bioactivators from the National Cancer Institute (NCI) list of compounds. The
      most potent NCI hit illustrated 6.3-fold GK activation at 10 MUM. These results
      demonstrated that our virtual screening protocol was able to identify novel GK
      activator leads for subsequent development into potential antidiabetic agents.

PMID- 25574767
TI  - Parathyroid adenoma in a young female presenting as recurrent acute pancreatitis
      with a brown tumour of the mandible-A case study.
AB  - INTRODUCTION: Primary hyperparathyroidism is usually seen in females above the
      age of 50 years, with a prevalence of 21/1000,(1) whereas the incidence in
      patients aged 12-28 years is less than 5%.(2) A solitary adenoma is responsible
      for 80% of cases of primary hyperparathyroidism.(3) Primary hyperparathyroidism
      is most commonly asymptomatic.(4) The incidence of acute pancreatitis associated
      with hyperparathyroidism is less than 10%.(5,6) The incidence of
      hyperparathyroidism associated with a Brown tumour is less than 5%.(7)
      PRESENTATION OF CASE: A 19 year old female patient presented with recurrent acute
      pancreatitis and swelling over the mandible. Complete investigative workup
      revealed a solitary parathyroid adenoma causing hyperparathyroidism. Surgical
      exploration with excision of the parathyroid adenoma was performed, following
      which the patient recovered uneventfully. DISCUSSION: The patient was initially
      managed as a case of acute pancreatitis, and although not suspected initially, a
      high index of suspicion for hyperparathyroidism developed after a biopsy of the
      mandibular swelling showed the presence of osteoclastic giant cells indicating
      the possibility of a Brown tumour. Further investigations then revealed the
      presence of a solitary parathyroid adenoma with coexistent hyperparathyroidism
      which was then managed surgically. CONCLUSION: The young age of the patient, and
      her presentation with acute pancreatitis and a Brown tumour of the mandible make
      this an extremely rare presentation of parathyroid adenoma.

PMID- 25574768
TI  - Retained barium in the appendix or right ureteric colic? A case report of
      surgeons dilemma.
AB  - INTRODUCTION: Retention of barium in the vermiform appendix for more than 72h
      following barium meal study is uncommon. It may produce undue concern for
      increased risk for appendicitis and even prophylactic appendectomies have been
      performed for this. PRESENTATION OF CASE: We encountered one such patient who
      presented with X-ray plate suggestive of tubular radio-opacity in the right iliac
      fossa region. The patient had episodes of severe pain in the right lower abdomen
      for which he underwent barium meal study. Further evaluation and investigations
      established the diagnosis as, a case of recurrent right ureteric colic with
      retained barium in the appendix. DISCUSSION: Review of the literature suggests
      that, in absence of acute appendicitis there is no role of appendectomy, even in
      a case of retained barium in the appendix. CONCLUSION: If atypical presentation
      is there, they should be appropriately further investigated.

PMID- 25574769
TI  - Laparoscopic treatment of intussusception.
AB  - INTRODUCTION: The success of laparoscopic approach in children has encouraged the
      application of this technique in young (<2 years) children with non-complicated
      intussusception. MATERIAL AND METHOD: A retrospective analysis of our database
      provided a total of 4 patients who underwent laparoscopic reduction of intestinal
      intussusception between 8/2008 and 4/2013. A comprehensive review of each case
      was done including the video description of the laparoscopic technique of one of
      them. RESULTS: Four patients (2 boys) were treated by laparoscopy for intestinal
      intussusception. Mean age was 9 months (5-20 months). Delay time between initial
      symptoms and diagnosis and between diagnosis and surgery were 3.5 days and 6h
      respectively. Mean operative time was 35min. There were no conversions. There
      were no complications. Patients were discharged after 2.5 days (2-4 days). We
      herein report (video) the laparoscopic approach in a 5 month male child who
      suffered from a ileocecal intussusception. A 10mm trocar was placed in the left
      lower quadrant and two 5mm trocars were placed in the upper left quadrant and
      suprapubic just to the right midline. The cause of the intussusception was
      identified and the bowel was reduced. A concomitant appendectomy was performed.
      CONCLUSION: Laparoscopic reduction of intussusception appears to be a safe
      procedure, in young children with uncomplicated intussusception.

PMID- 25574770
TI  - Presentation of case: Bladder cancer in an 18 year old female patient.
AB  - INTRODUCTION: Bladder cancers are not very common in the young population below
      20 years of age, especially in those who have not been exposed to chemotherapy,
      bladder augmentation surgery and other known risk factors. By highlighting this
      case we hope to raise awareness in the medical community, that the symptom of
      visible haematuria can potentially be due to a bladder malignancy and therefore
      this should be thoroughly investigated. PRESENTATION OF CASE: An 18-year-old
      female presented with intermittent macroscopic haematuria and non-specific
      abdominal pain. Physical examination and routine blood tests were normal. An
      ultrasound scan initially showed a bladder wall lesion, which a flexible
      cystoscopy confirmed. Histology revealed grade 2 papillary transitional cell
      carcinoma of the bladder with no invasion into the lamina propria (G2pTa TCCB).
      DISCUSSION: We recognise through our literature review that paediatric bladder
      cancers are not commonly reported in the UK. In our paper we highlight the
      relevant major studies that have been carried out world-wide, the reported
      incidence so far and gaps in the evidence base. CONCLUSION: Despite the dearth of
      data about paediatric bladder malignancies there is enough case-based evidence,
      from world-wide sources, to support that bladder cancer must be suspected in the
      event of macroscopic haematuria. Ultrasound and cystoscopy are the standard
      diagnostic tools for bladder tumours. Endoscopic resection of the tumour followed
      up by interval ultrasound scans and flexible cystoscopy checks remain the
      mainstay of treatment hitherto.

PMID- 25574771
TI  - Kinetics of cytokine expression in bovine PBMCs and whole blood after in vitro
      stimulation with foot-and-mouth disease virus (FMDV) antigen.
AB  - The interest in analysing antigen-specific cytokine responses has substantially
      increased in recent years, in part due to their use in assessing vaccine
      efficacy. In the present study, the kinetics of IL-2, IL-4 and IFN-gamma
      expression was determined in bovine PBMCs by real-time PCR and in whole blood by
      cytokine-release assay after in vitro stimulation with recall foot-and-mouth
      disease virus (FMDV) antigen. The results showed that the cytokine mRNA of IL-2
      and IFN-gamma in PBMCs were induced early (peak induction at 6 h), whereas the IL
      4 mRNA showed delayed induction (peaked at 24 h). In contrast, the kinetics of
      cytokine proteins in whole blood was different and required the accumulation of
      the proteins before being optimally detected. The peak accumulation of cytokine
      protein in whole blood was recorded at 72 h for IL-2 and IL-4, and 96 h for IFN
      gamma. The findings of this study are of importance when selecting an optimal
      time points for measuring antigen-specific cytokine expression in cattle.

PMID- 25574772
TI  - Molecular analysis of single room humidifier bacteriology.
AB  - Portable, single-room humidifiers are commonly used in homes for comfort and
      health benefits, but also create habitats for microbiology. Currently there is no
      information on home humidifier microbiology aside from anecdotal evidence of
      infection with opportunistic pathogens and irritation from endotoxin exposure. To
      obtain a broader perspective on humidifier microbiology, DNAs were isolated from
      tap source waters, tank waters, and biofilm samples associated with 26
      humidifiers of ultrasonic and boiling modes of operation in the Front Range of
      Colorado. Humidifiers sampled included units operated by individuals in their
      homes, display models continuously operated by a retail store, and new
      humidifiers operated in a controlled laboratory study. The V1V2 region of the
      rRNA gene was amplified and sequenced to determine the taxonomic composition of
      humidifier samples. Communities encountered were generally low in richness and
      diversity and were dominated by Sphingomonadales, Rhizobiales, and
      Burkholderiales of the Proteobacteria, and MLE1-12, a presumably non
      photosynthetic representative of the cyanobacterial phylum. Very few sequences of
      potential health concern were detected. The bacteriology encountered in source
      waters sampled here was similar to that encountered in previous studies of
      municipal drinking waters. Source water bacteriology was found to have the
      greatest effect on tank water and biofilm bacteriology, an effect confirmed by a
      controlled study comparing ultrasonic and boiler humidifiers fed with tap vs.
      treated (deionized, reverse osmosis, 0.2 MUm filtered) water over a period of two
      months. 

PMID- 25574773
TI  - The roles of CRISPR-Cas systems in adaptive immunity and beyond.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) and
      accompanying Cas proteins constitute the adaptive CRISPR-Cas immune system in
      bacteria and archaea. This DNA-encoded, RNA-mediated defense system provides
      sequence-specific recognition, targeting and degradation of exogenous nucleic
      acid. Though the primary established role of CRISPR-Cas systems is in bona fide
      adaptive antiviral defense in bacteria, a growing body of evidence indicates that
      it also plays critical functional roles beyond immunity, such as endogenous
      transcriptional control. Furthermore, benefits inherent to maintaining genome
      homeostasis also come at the cost of reduced uptake of beneficial DNA, and
      preventing strategic adaptation to the environment. This opens new avenues for
      the investigation of CRISPR-Cas systems and their functional characterization
      beyond adaptive immunity. 

PMID- 25574775
TI  - Proton-induced damage on 2-aminooxazole, a potential prebiotic compound.
AB  - Among the complex organic molecules detected in space, in the interstellar
      medium, on meteorites or comets, special interest is devoted to the potentially
      exobiologic-relevant species. In the hypothesis, widely discussed, of a possible
      exogen origin of life, the transport of such compounds and their survival is
      indeed a fundamental question. Recently, suggestion has been made that 2
      aminooxazole could be a possible precursor of RNA nucleotides on early earth and
      its stability to UV radiation or to collisions may be determinant. We have thus
      undertaken a detailed theoretical study of the charge transfer collision dynamics
      induced by the impact of 2-aminooxazole with protons, which could be an important
      process in particular in proton-rich environments. The theoretical treatment has
      been developed through ab initio quantum chemistry molecular calculations
      followed by semiclassical collision dynamics. The results are compared to
      previous investigations on DNA and RNA building blocks in order to extract some
      qualitative trends in the damage of prebiotic species under spatial radiation. 

PMID- 25574776
TI  - From ring-in-ring to sphere-in-sphere: self-assembly of discrete 2D and 3D
      architectures with increasing stability.
AB  - Directed by increasing the density of coordination sites (DOCS) to increase the
      stability of assemblies, discrete 2D ring-in-rings and 3D sphere-in-sphere were
      designed and self-assembled by one tetratopic pyridyl-based ligand with 180
      degrees  diplatinum(II) acceptors and naked Pd(II), respectively. The high DOCS
      resulted by multitopic ligand provided more geometric constraints to form
      discrete structures with high stability. Compared to reported supramolecular
      hexagons and polyhedra by ditotpic ligands, the self-assembly of such giant
      architectures using multitopic ligands with all rigid backbone emphasized the
      structural integrity with precise preorganization of entire architecture, and
      required elaborate synthetic operations for ligand preparation. In-depth
      structural characterization was conducted to support desired structures,
      including multinuclear NMR ((1)H, (31)P, and (13)C) analysis, 2D NMR spectroscopy
      (COSY and NOESY), diffusion-ordered NMR spectroscopy (DOSY), multidimensional
      mass spectrometry, TEM and AFM. Furthermore, a quantitative definition of DOCS
      was proposed to compare 2D and 3D structures and correlate the DOCS and stability
      of assemblies in a quantitative manner. Finally, ring-in-rings in DMSO or DMF
      could undergo hierarchical self-assembly into the ordered nanostructures and
      generated translucent supramolecular metallogels. 

PMID- 25574774
TI  - Enzyme dynamics from NMR spectroscopy.
AB  - CONSPECTUS: Biological activities of enzymes, including regulation or
      coordination of mechanistic stages preceding or following the chemical step, may
      depend upon kinetic or equilibrium changes in protein conformations. Exchange of
      more open or flexible conformational states with more closed or constrained
      states can influence inhibition, allosteric regulation, substrate recognition,
      formation of the Michaelis complex, side reactions, and product release. NMR
      spectroscopy has long been applied to the study of conformational dynamic
      processes in enzymes because these phenomena can be characterized over multiple
      time scales with atomic site resolution. Laboratory-frame spin-relaxation
      measurements, sensitive to reorientational motions on picosecond-nanosecond time
      scales, and rotating-frame relaxation-dispersion measurements, sensitive to
      chemical exchange processes on microsecond-millisecond time scales, provide
      information on both conformational distributions and kinetics. This Account
      reviews NMR spin relaxation studies of the enzymes ribonuclease HI from
      mesophilic (Escherichia coli) and thermophilic (Thermus thermophilus) bacteria,
      E. coli AlkB, and Saccharomyces cerevisiae triosephosphate isomerase to
      illustrate the contributions of conformational flexibility and dynamics to
      diverse steps in enzyme mechanism. Spin relaxation measurements and molecular
      dynamics (MD) simulations of the bacterial ribonuclease H enzymes show that the
      handle region, one of three loop regions that interact with substrates,
      interconverts between two conformations. Comparison of these conformations with
      the structure of the complex between Homo sapiens ribonuclease H and a DNA:RNA
      substrate suggests that the more closed state is inhibitory to binding. The large
      population of the closed conformation in T. thermophilus ribonuclease H
      contributes to the increased Michaelis constant compared with the E. coli enzyme.
      NMR spin relaxation and fluorescence spectroscopy have characterized a
      conformational transition in AlkB between an open state, in which the side chains
      of methionine residues in the active site are disordered, and a closed state, in
      which these residues are ordered. The open state is highly populated in the
      AlkB/Zn(II) complex, and the closed state is highly populated in the
      AlkB/Zn(II)/2OG/substrate complex, in which 2OG is the 2-oxoglutarate cosubstrate
      and the substrate is a methylated DNA oligonucleotide. The equilibrium is shifted
      to approximately equal populations of the two conformations in the
      AlkB/Zn(II)/2OG complex. The conformational shift induced by 2OG ensures that 2OG
      binds to AlkB/Zn(II) prior to the substrate. In addition, the opening rate of the
      closed conformation limits premature release of substrate, preventing generation
      of toxic side products by reaction with water. Closure of active site loop 6 in
      triosephosphate isomerase is critical for forming the Michaelis complex, but
      reopening of the loop after the reaction is (partially) rate limiting. NMR spin
      relaxation and MD simulations of triosephosphate isomerase in complex with
      glycerol 3-phosphate demonstrate that closure of loop 6 is a highly correlated
      rigid-body motion. The MD simulations also indicate that motions of Gly173 in the
      most flexible region of loop 6 contribute to opening of the active site loop for
      product release. Considered together, these three enzyme systems illustrate the
      power of NMR spin relaxation investigations in providing global insights into the
      role of conformational dynamic processes in the mechanisms of enzymes from
      initial activation to final product release.

PMID- 25574778
TI  - Enhanced thermoelectric properties in bulk nanowire heterostructure-based
      nanocomposites through minority carrier blocking.
AB  - To design superior thermoelectric materials the minority carrier blocking effect
      in which the unwanted bipolar transport is prevented by the interfacial energy
      barriers in the heterogeneous nanostructures has been theoretically proposed
      recently. The theory predicts an enhanced power factor and a reduced bipolar
      thermal conductivity for materials with a relatively low doping level, which
      could lead to an improvement in the thermoelectric figure of merit (ZT). Here we
      show the first experimental demonstration of the minority carrier blocking in
      lead telluride-silver telluride (PbTe-Ag2Te) nanowire heterostructure-based
      nanocomposites. The nanocomposites are made by sintering PbTe-Ag2Te nanowire
      heterostructures produced in a highly scalable solution-phase synthesis. Compared
      with Ag2Te nanowire-based nanocomposite produced in similar method, the PbTe
      Ag2Te nanocomposite containing ~5 atomic % PbTe exhibits enhanced Seebeck
      coefficient, reduced thermal conductivity, and ~40% improved ZT, which can be
      well explained by the theoretical modeling based on the Boltzmann transport
      equations when energy barriers for both electrons and holes at the
      heterostructure interfaces are considered in the calculations. For this p-type
      PbTe-Ag2Te nanocomposite, the barriers for electrons, that is, minority carriers,
      are primarily responsible for the ZT enhancement. By extending this approach to
      other nanostructured systems, it represents a key step toward low-cost solution
      processable nanomaterials without heavy doping level for high-performance
      thermoelectric energy harvesting. 

PMID- 25574777
TI  - Can we predict failure in couple therapy early enough to enhance outcome?
AB  - Feedback to therapists based on systematic monitoring of individual therapy
      progress reliably enhances therapy outcome. An implicit assumption of therapy
      progress feedback is that clients unlikely to benefit from therapy can be
      detected early enough in the course of therapy for corrective action to be taken.
      To explore the possibility of using feedback of therapy progress to enhance
      couple therapy outcome, the current study tested whether weekly therapy progress
      could detect off-track clients early in couple therapy. In an effectiveness trial
      of couple therapy, 136 couples were monitored weekly on relationship satisfaction
      and an expert derived algorithm was used to attempt to predict eventual therapy
      outcome. As expected, the algorithm detected a significant proportion of couples
      who did not benefit from couple therapy at Session 3, but prediction was
      substantially improved at Session 4 so that eventual outcome was accurately
      predicted for 70% of couples, with little improvement of prediction thereafter.
      More sophisticated algorithms might enhance prediction accuracy, and a trial of
      the effects of therapy progress feedback on couple therapy outcome is needed. 

PMID- 25574779
TI  - Reaction-based turn-on electrochemiluminescent sensor with a ruthenium(II)
      complex for selective detection of extracellular hydrogen sulfide in rat brain.
AB  - Hydrogen sulfide (H2S) has been drawing increasing attention because it plays an
      important role in the nervous system and has been deemed as a third endogenous
      gas signal molecule besides nitric oxide (NO) and carbon monoxide (CO). In this
      study, using a ruthenium complex, [Ru(bpy)2(bpy-DPA)Cu](4+) (where bpy = 2,2'
      bipyridine and bpy-DPA = 4-methyl-4'-[N,N-bis(2-picolyl)aminomethylene]-2,2'
      bipyridine) as recognition unit, we report a new reaction-based turn-on
      electrochemiluminescent (ECL) sensor to selectively detect extracellular H2S in
      rat brain, coupled with in vivo microdialysis for dialysate sampling. To prepare
      the sensor for sensing endogenous H2S, [Ru(bpy)2(bpy-DPA)](2+) is first designed
      and synthesized, showing high ECL efficiency with tri-n-propylamine (TPA) as a
      coreactant and quenching after reaction with Cu(2+) (forming [Ru(bpy)2(bpy
      DPA)Cu](4+)). Then a Nafion membrane is coated on the surface of glassy carbon
      (GC) electrode and [Ru(bpy)2(bpy-DPA)Cu](4+) is confined onto the Nafion membrane
      through ion exchange. The resulting [Ru(bpy)2(bpy-DPA)Cu](4+)/Nafion/GC sensor
      exhibits a low ECL signal. The [Ru(bpy)2(bpy-DPA)Cu](4+)/Nafion/GC sensor
      demonstrates enhanced ECL signal after reacting with volatile H2S due to the high
      affinity binding between sulfur and Cu(2+), returning to [Ru(bpy)2(bpy
      DPA)](2+)/Nafion/GC. The changes of ECL signal at the sensor depend linearly on
      the concentration of Na2S in the range from 0.5 to 10 MUM, with a detection limit
      of 0.25 MUM. Moreover, the sensor demonstrates high selectivity, free from
      interference especially by other nonvolatile thiol-containing species, such as
      cysteine and glutathione. The basal dialysate level of H2S in the microdialysate
      from the cortex of adult male Sprague-Dawley rats is determined to be 2.3 +/- 0.9
      MUM (n = 4). This method is reliable and is envisaged to help understand the
      regulation of H2S in physiological and pathological events. 

PMID- 25574780
TI  - Reduction mechanism for Eu ions in Al2O3-containing glasses by heat treatment in
      H2 gas.
AB  - Superior functional glasses doped with rare-earth ions have been prepared by
      controlling the valence states of rare-earth ions. However, recent work has
      revealed unresolved questions about the controlling mechanism of rare-earth ions'
      valence states. To address these questions, oxide glasses with and without Al2O3
      and doped with Eu(3+) ions were prepared by a melting process; then, the valence
      states of Eu(3+) ions were investigated during heating under a hydrogen
      environment. The Eu(3+) ions were reduced to Eu(2+) only in the glass containing
      Al(3+) ions; the reduction occurred in the center of the glass over a short
      heating period. It was discovered that the reduction of Eu(3+) ions concurrently
      occurred with the formation of OH bonds which were bound with Al(3+) ions.
      Considering this and the data for the H2 gas diffusion through the glass, we
      conclude that diffusing H2 gas molecules react with Al-O(-) bonds surrounding
      Eu(3+) ions to form AlOH bonds and reduce Eu(3+) ions to Eu(2+) via the extracted
      electrons. When H2 reacts with a glass structure, that hydrogen has transformed
      into -OH bonds and the hydrogen concentration in the glass decreases. In order to
      make up the lost hydrogen, more hydrogen molecules can enter into the glass,
      resulting in the fast reduction of Eu(3+) ions in the center of the glass. 

PMID- 25574782
TI  - Results and prognostic factors for visual improvement after pars plana vitrectomy
      for idiopathic epiretinal membrane.
AB  - BACKGROUND: Pars plana vitrectomy (PPV) for peeling epiretinal membrane is now
      generally recommended with better vision compared with historical series. This
      study reports the results and prognostic factors for postoperative visual
      improvement in a contemporary series. METHODS: Demographic data, best-corrected
      visual acuity (BCVA), and optical coherence tomography parameters of 504 eyes
      (495 patients) that underwent PPV for idiopathic epiretinal membrane from 2003 to
      2012 were tabulated. The primary outcome measure was proportion of eyes with
      improvement of at least two Snellen lines or more of BCVA 3, 6, and 12 months
      after PPV. A secondary outcome was prognostic factors for improvement of at least
      two Snellen lines or more of BCVA after PPV at 3, 6, and 12 months. RESULTS:
      There was a gain of >=2 lines in 211 of 504 eyes (41.7%) at 3 months, in 84 of
      242 eyes (34.7%) at 6 months, and 112 of 233 eyes (48.1%) at 12 months after PPV
      and epiretinal membrane peeling surgery. Poorer preoperative BCVA and
      preoperative pseudophakic lens status were associated with better visual
      improvement at 3 months. CONCLUSION: The lower frequency of moderate BCVA
      improvement for those with good preoperative BCVA and phakic lens status might
      influence visual improvement, and therefore, a recommendation for surgery.

PMID- 25574781
TI  - HIV, violence and women: unmet mental health care needs.
AB  - BACKGROUND: HIV-infected (HIV+) women have high rates of Gender Based Violence
      (GBV). Studies of GBV find that approximately 50-90% of survivors develop mood
      and anxiety disorders. Given that women in sub-Saharan African constitute the
      largest population of HIV+ individuals in the world and the region's high GBV
      prevalence, mental health research with HIV+ women affected by GBV (HIV+GBV+) in
      this region is urgently needed. METHODS: Qualitative methods were used to
      evaluate the mental health care needs of HIV+GBV+ female patients at an HIV
      clinic in the Kisumu County, Kenya. Thirty in-depth interviews and four focus
      groups were conducted with patients, healthcare providers and community leaders.
      Interviews were transcribed, translated and analyzed using qualitative data
      software. RESULTS: Respondents stated that physical, sexual and emotional
      violence against HIV+ women was widely prevalent and perpetrated primarily by
      untested husbands accusing a wife of marital infidelity following her positive
      HIV test result. Mental health problems among HIV+GBV+ women included depressive,
      anxiety, traumatic stress symptoms and suicidal thoughts. Participants opined
      that emotional distress from GBV not only caused HIV treatment default, but also
      led to poor HIV health even if adherent. Respondents agreed that mental health
      treatment was needed for HIV+GBV+ women; most agreed that the best treatment
      modality was individual counseling delivered weekly at the HIV clinic.
      LIMITATIONS: Emotional distress may be higher and/or more varied among HIV+GBV+
      women who are not engaged in HIV care. CONCLUSIONS: Mental health care is needed
      and desired by HIV+GBV+ women in Kisumu County, Kenya.

PMID- 25574783
TI  - Choroidal volume in branch retinal vein occlusion before and after intravitreal
      anti-VEGF injection.
AB  - PURPOSE: The aim of this study is to evaluate the subfoveal choroidal volume
      change in the patients with branch retinal vein occlusion before and after
      intravitreal anti-vascular endothelial growth factor injection using the enhanced
      depth imaging optical coherence tomography. METHODS: We measured the bilateral
      subfoveal choroidal volume in 15 patients (mean age, 64.47 +/- 7.13 years) with
      unilateral branch retinal vein occlusion by using the enhanced depth imaging
      methods of the Spectralis optical coherence tomography system. After an injection
      of intravitreal bevacizumab, we measured the subfoveal choroidal volume of the
      eye with regressed macular edema. RESULTS: The mean subfoveal choroidal volume
      measured in 15 eligible eyes of 15 patients was 7.74 +/- 0.70 mm, which was
      significantly greater than the volume of the fellow eyes (6.38 +/- 0.69 mm; P =
      0.001, Wilcoxon signed-rank test). The subfoveal choroidal volume of the eye with
      regressed macular edema was 6.56 +/- 0.79 mm, which was significantly lower than
      the volume before the treatment (P = 0.001, Wilcoxon signed-rank test).
      CONCLUSION: The subfoveal choroidal volume of the branch retinal vein occlusion
      eyes was significantly greater than the volume of the fellow eyes and decreased
      significantly after an intravitreal anti-vascular endothelial growth factor
      treatment.

PMID- 25574784
TI  - CLINICAL COURSE OF DIABETIC RETINOPATHY IN KOREAN TYPE 2 DIABETES AFTER BARIATRIC
      SURGERY: A Pilot Study.
AB  - PURPOSE: To assess the changes in diabetic retinopathy (DR) in Type 2 diabetes
      (T2DM) patients after bariatric surgery. METHODS: Consecutive 20 patients with
      T2DM who underwent bariatric surgery and were followed for at least 12 months
      were enrolled. The case history was reviewed retrospectively, and laboratory data
      were assessed at baseline and every 3 months postoperatively. Two retinal
      specialists evaluated the severity of DR with dilated fundus examination
      preoperatively and postoperatively. Factors associated with DR progression were
      assessed. RESULTS: During the follow-up period, 2 of 12 patients without DR and 2
      of 3 patients with mild nonproliferative DR before surgery developed moderate
      nonproliferative DR. All five patients with moderate nonproliferative DR or worse
      preoperatively had progression requiring intervention. Preexisting DR (P = 0.005)
      and albuminuria (P = 0.01) were identified as associated with DR progression. Six
      patients (30%) entered remission of T2DM, but remission of T2DM could not halt
      the DR progression. CONCLUSION: Diabetic retinopathy progression can occur in
      patients with or without before DR after bariatric surgery, regardless of
      remission of T2DM. All patients with T2DM should be examined regularly by an
      ophthalmologist postoperatively, and more carefully patients with previous DR or
      albuminuria.

PMID- 25574785
TI  - Fundus changes in branch retinal vein occlusion.
AB  - PURPOSE: To investigate systematically the retinal changes in branch retinal vein
      occlusion (BRVO) and their natural history. METHODS: The study comprised 214
      consecutive patients with BRVO (144 major BRVO and 72 macular BRVO eyes) seen
      within 3 months of onset. Ophthalmic evaluation at initial and follow-up visits
      included recording visual acuity, visual fields, and detailed anterior segment
      and fundus examinations and fluorescein fundus angiography. RESULTS: Initially,
      retinal hemorrhages were moderate to severe in the perifovea and macula in at
      least 65% in major and 52% in macular BRVO; at the fovea, it was 51% in major and
      36% in macular BRVO. Initially, macular edema was more marked in major BRVO than
      in macular BRVO (P = 0.007). Major BRVO had a significantly higher rate of
      development of serous macular detachment (P = 0.002), epiretinal membrane (P =
      0.008), serous retinal detachment (P = 0.002), perivenous sheathing (P < 0.0001),
      optic disk pallor (P < 0.0001), and lipid deposit (P < 0.0001) compared with
      macular BRVO. Retinal and disk neovascularization was seen only in major BRVO.
      The time to resolution of BRVO was significantly longer for major BRVO compared
      with macular BRVO (P = 0.0002). CONCLUSION: Major and macular BRVOs are two
      distinct clinical entities. Initial and final fundus findings in the two types
      differ markedly.

PMID- 25574786
TI  - Incidence of outer retinal tubulation in ranibizumab-treated age-related macular
      degeneration.
AB  - PURPOSE: To investigate the incidence of outer retinal tubulation (ORT) in
      ranibizumab-treated neovascular age-related macular degeneration patients.
      METHODS: We included 480 consecutive patients (546 eyes) with neovascular age
      related macular degeneration, who were treated with variable-dosing intravitreal
      ranibizumab, evaluated with spectral domain optical coherence tomography, and
      followed-up for a minimum period of 6 months. Optical coherence tomographies were
      evaluated for the first appearance of ORT, precursor signs, and type of
      underlying lesion. Visual acuity was also recorded. RESULTS: Outer retinal
      tubulation was observed in 30% of eyes during a mean follow-up period of 26.7
      months (SD, 13.5). Kaplan-Meier survival analysis revealed that the ORT incidence
      (2.5, 17.5, 28.4, and 41.6% at baseline, after 1, 2, and 4 years, respectively)
      continuously increased, despite visually effective anti-vascular endothelial
      growth factor treatment. Outer retinal tubulation was associated with a poorer
      functional benefit. Lower baseline visual acuity was associated with a higher
      risk of developing ORT. CONCLUSION: Incidence of ORT continuously increases
      despite visually optimal anti-vascular endothelial growth factor treatment of age
      related macular degeneration. Outer retinal tubulation might be considered a
      prognostic factor for functional outcome and is relevant to avoid overtreatment.

PMID- 25574787
TI  - Repeated intravitreal dexamethasone implant (Ozurdex) for diabetic macular edema.
AB  - PURPOSE: To evaluate the effects of repeated intravitreal dexamethasone implant.
      METHODS: We reviewed the charts of 12 patients with diabetic macular edema, who
      received at least 2 intravitreal Ozurdex (0.7 mg) on an "as needed" basis. Main
      outcome measures included changes in best-corrected visual acuity, central
      macular thickness, retreatment interval, and incidence of side effects. RESULTS:
      A total of 15 eyes of 12 patients (6 men, 6 women; mean age 62 +/- 12 years) were
      included. Retreatment was judged necessary after mean of 7.8 +/- 4.1 months from
      the first Ozurdex (median, 6 months) (15 of 15 eyes), mean of 4.8 +/- 0.9 months
      from the second Ozurdex (median, 5 months) (7 of 15 eyes), mean of 5.3 +/- 1.5
      months from the third Ozurdex (median, 5 months) (3 of 15 eyes), and mean of 5.6
      +/- 2 months from the fourth Ozurdex (median, 5 months) (3 of 15 eyes). Mean
      baseline best-corrected visual acuity was 0.67 +/- 0.33 logMAR in the overall
      diabetic macular edema population; it significantly improved to 0.53 +/- 0.31
      logMAR after mean of 40.9 +/- 18.2 days from the first Ozurdex (peaking efficacy)
      (P < 0.001), to 0.53 +/- 0.29 logMAR after mean of 34.4 +/- 9.0 days from the
      second Ozurdex (peaking efficacy) (P < 0.003), and stabilized to 0.62 +/- 0.26
      logMAR after mean of 29.8 +/- 12.1 days from the third Ozurdex (peaking efficacy)
      (P = 0.05), to 0.5 +/- 0.26 logMAR after mean of 36.3 +/- 3.2 days from the
      fourth Ozurdex (peaking efficacy) (P = 0.2), and to 0.50 +/- 0.26 logMAR after
      mean of 37.0 +/- 2.6 days from the fifth Ozurdex (peaking efficacy) (P = 0.2).
      Mean baseline central macular thickness significantly decreased from 546 +/- 139
      MUm to 292 +/- 43 MUm at 39.4 +/- 17.9 days from the first Ozurdex (peaking
      efficacy) (P < 0.001), to 297 +/- 47 MUm at 33 +/- 9.4 days from the second
      Ozurdex (peaking efficacy) (P < 0.001), to 293 +/- 22 MUm at 29.8 +/- 12.1 days
      from the third Ozurdex (peaking efficacy) (P = 0.01), and stabilized to 309 +/-
      35 MUm at 36.3 +/- 3.2 days from the fourth Ozurdex (peaking efficacy) (P = 0.1),
      and to 295 +/- 7 MUm at 37.0 +/- 2.6 days from the fifth Ozurdex (peaking
      efficacy) (P = 0.1). No serious adverse events were observed; three eyes
      developed a transient intraocular pressure increase, and cataract was extracted
      in one eye. CONCLUSION: Repeated intravitreal Ozurdex on an "as needed" basis
      with a variable retreatment interval may produce long-term clinically meaningful
      benefits in the treatment of diabetic macular edema, without other significant
      side effects than expected after intraocular corticosteroid treatment.

PMID- 25574788
TI  - Sclerochoroidal calcification: clinical features, outcomes, and relationship with
      hypercalcemia and parathyroid adenoma in 179 eyes.
AB  - PURPOSE: To describe the clinical features and long-term ophthalmic and systemic
      findings in patients with sclerochoroidal calcification (SCC). METHODS:
      Retrospective non-interventional clinical chart review of 179 eyes of 118
      patients with SCC to evaluate for the relationship of SCC with systemic calcium
      metabolic abnormalities. RESULTS: The mean patient age at diagnosis was 69 years.
      There were 47 (40%) men and 71 (60%) women of Caucasian (n = 116, 98%) and
      Hispanic (n = 2, 2%) heritage. The condition was unilateral in 57 patients (48%)
      and bilateral in 61 (52%), with a mean of 1.6 lesions per eye (range, 1-7 lesions
      per eye). The referring diagnosis was choroidal nevus (n = 23, 20%), melanoma (n
      = 15, 13%), lymphoma (n = 12, 10%), metastasis (n = 6, 5%), osteoma (n = 4, 3%),
      SCC (n = 6, 5%), and no diagnosis (n = 51, 43%). Of 277 SCC lesions, the most
      common location was superotemporal quadrant (n = 191, 69%). The largest lesion
      per eye demonstrated mean basal diameter of 3.6 mm and thickness of 1.8 mm, with
      yellow or white color (n = 150 lesions, 84%) and located superiorly (n = 105,
      61%) at the retinal vascular arcade or near the equator (n = 161, 94%). The
      lesion demonstrated overlying focal choroidal atrophy (n = 63, 35%) and retinal
      pigment epithelium atrophy (n = 88, 49%). There was no case of subretinal fluid,
      hemorrhage, or choroidal neovascular membrane. At mean 4 years follow up, there
      was no lesion enlargement, decalcification, or related subretinal
      fluid/hemorrhage, choroidal neovascularization, or vision loss. Ocular treatment
      was not necessary in any case. Systemic outcomes revealed hyperparathyroidism (n
      = 9/33, 27%) with parathyroid adenoma (n = 5/33, 15%), Bartter syndrome (n =
      1/53, 2%), or Gitelman syndrome (n = 6/53, 11%). CONCLUSIONS: Sclerochoroidal
      calcification is a stable deposition of calcium in the sclera that, unlike
      choroidal osteoma, has minimal risk for vision loss. All patients with SCC should
      be evaluated for underlying systemic calcium disorders, especially parathyroid
      and renal metabolic conditions.

PMID- 25574789
TI  - Increased prepubertal body weight enhances leptin sensitivity in
      proopiomelanocortin and neuropeptide y neurons before puberty onset in female
      rats.
AB  - Pubertal onset may be advanced by obesity, with leptin potentially acting as a
      permissive factor. We hypothesized that having increased body weight (BW)
      prepubertally affects the ability of leptin to activate intracellular signaling
      pathways and modulate the expression of hypothalamic neuropeptides involved in
      reproduction and metabolism. Because being raised in small litters (SLs) tends to
      increase BW at weaning, female rats were raised in litters of 4 or large litters
      (LLs) of 12 pups. Leptin (3 MUg/g BW) or vehicle (saline) was injected sc at
      postnatal day (PND) 21 and 30. Rats raised in SLs weighed more at both ages, but
      relative visceral and subcutaneous fat was increased only on PND21. Serum leptin
      levels were not different at PND21 or PND30. At PND21, key elements of
      intracellular leptin signaling (phosphorylated signal transducer and activator of
      transcription 3 and phosphorylated Akt [p-Akt]) were lower in SL than in LL rats.
      Leptin injection stimulated phosphorylated signal transducer and activator of
      transcription 3 in both groups, with a greater increase in LL, whereas p-Akt rose
      only in SL rats. At PND30, basal leptin signaling did not differ between LL and
      SL rats. Leptin activation of Akt was similar at 45 minutes, but at 2 hours p-AKT
      levels were higher in SL than in LL rats, as was the decrease in neuropeptide Y
      mRNA and increase in pro-opiomelanocortin mRNA levels. No change in the
      reproductive axis was found. Thus, being raised in SLs increases BW and visceral
      body fat content, fails to increase plasma leptin concentrations, and increases
      the leptin responsiveness of both neuropeptide Y and pro-opiomelanocortin cells
      in the prepubertal hypothalamus. 

PMID- 25574791
TI  - Current status of robotic simulators in acquisition of robotic surgical skills.
AB  - PURPOSE OF REVIEW: This article provides an overview of the current status of
      simulator systems in robotic surgery training curriculum, focusing on available
      simulators for training, their comparison, new technologies introduced in
      simulation focusing on concepts of training along with existing challenges and
      future perspectives of simulator training in robotic surgery. RECENT FINDINGS:
      The different virtual reality simulators available in the market like dVSS, dVT,
      RoSS, ProMIS and SEP have shown face, content and construct validity in robotic
      skills training for novices outside the operating room. Recently, augmented
      reality simulators like HoST, Maestro AR and RobotiX Mentor have been introduced
      in robotic training providing a more realistic operating environment, emphasizing
      more on procedure-specific robotic training . Further, the Xperience Team
      Trainer, which provides training to console surgeon and bed-side assistant
      simultaneously, has been recently introduced to emphasize the importance of
      teamwork and proper coordination. SUMMARY: Simulator training holds an important
      place in current robotic training curriculum of future robotic surgeons. There is
      a need for more procedure-specific augmented reality simulator training,
      utilizing advancements in computing and graphical capabilities for new
      innovations in simulator technology. Further studies are required to establish
      its cost-benefit ratio along with concurrent and predictive validity.

PMID- 25574792
TI  - Are structured curriculums for laparoscopic training useful? A review of current
      literature.
AB  - PURPOSE OF REVIEW: To review previous, recent, and future perspectives of
      laparoscopic training. RECENT FINDINGS: Published studies showed the importance
      and benefits of training programmes in urologic laparoscopic surgery. In
      addition, laparoscopy at present can be performed for most of surgical modalities
      specifically in experienced centres. Thereof, well designed training programmes
      are needed for performing all-purpose laparoscopic surgeries. Additionally,
      training programmes may help to reduce the laparoscopic complications. However,
      training programmes should include some steps for performing future surgeries.
      Thus, structured training programmes can be more useful for urologists and hence
      should be preferred. Nonetheless, structured training programmes can be difficult
      to perform and need patience with long learning curve. These can help urologists
      to prepare for their first urologic laparoscopic procedures. SUMMARY: Usage of
      laparoscopic procedures in urological field has been increasing parallel to
      developments in minimally invasive technologies worldwide. Therefore, there has
      been an increase in the numbers of urologists who want to learn laparoscopy. At
      this point, a structured curriculum for laparoscopic training comes into
      question. However, laparoscopic surgical modalities need to be trained, in large
      quantities. Training programmes can help surgeons learn and perform laparoscopy
      properly. However, these should be well designed and structured.

PMID- 25574790
TI  - Is Participation in Certain Sports Associated With Knee Osteoarthritis? A
      Systematic Review.
AB  - OBJECTIVE:   Information regarding the relative risks of developing knee
      osteoarthritis (OA) as a result of sport participation is critical for shaping
      public health messages and for informing knee-OA prevention strategies. The
      purpose of this systematic review was to investigate the association between
      participation in specific sports and knee OA. DATA SOURCES:   We completed a
      systematic literature search in September 2012 using 6 bibliographic databases
      (PubMed; Ovid MEDLINE; Journals@Ovid; American College of Physicians Journal
      Club; Cochrane Central Register of Controlled Trials, Cochrane Database of
      Systematic Review, Database of Abstracts of Reviews of Effects; and Ovid
      HealthStar), manual searches (4 journals), and reference lists (56 articles).
      STUDY SELECTION:   Studies were included if they met the following 4 criteria:
      (1) an aim was to investigate an association between sport participation and knee
      OA; (2) the outcome measure was radiographic knee OA, clinical knee OA, total
      knee replacement, self-reported diagnosis of knee OA, or placement on a waiting
      list for a total knee replacement; (3) the study design was case control or
      cohort; and (4) the study was written in English. Articles were excluded if the
      study population had an underlying condition other than knee OA. DATA EXTRACTION:
      One investigator extracted data (eg, group descriptions, knee OA prevalence,
      source of nonexposed controls). DATA SYNTHESIS:   The overall knee-OA prevalence
      in sport participants (n = 3759) was 7.7%, compared with 7.3% among nonexposed
      controls (referent group n = 4730, odds ratio [OR] = 1.1). Specific sports with a
      significantly higher prevalence of knee OA were soccer (OR = 3.5), elite-level
      long-distance running (OR = 3.3), competitive weight lifting (OR = 6.9), and
      wrestling (OR = 3.8). Elite-sport (soccer or orienteering) and nonelite-sport
      (soccer or American football) participants without a history of knee injury had a
      greater prevalence of knee OA than nonexposed participants. CONCLUSIONS:  
      Participants in soccer (elite and nonelite), elite-level long-distance running,
      competitive weight lifting, and wrestling had an increased prevalence of knee OA
      and should be targeted for risk-reduction strategies.

PMID- 25574793
TI  - Cerebrovascular events, secondary intracranial tumors, and mortality after
      radiotherapy for nonfunctioning pituitary adenomas: a subanalysis from the Dutch
      National Registry of Growth Hormone Treatment in Adults.
AB  - CONTEXT: Radiotherapy is frequently administered as adjuvant treatment in
      patients with clinically nonfunctioning pituitary adenomas (NFPAs). However,
      concerns have been raised about potential long-term side effects, including
      cerebrovascular events (CVEs) and secondary intracranial tumors. OBJECTIVE: The
      aim of this study was to analyze the risk of CVEs, secondary intracranial tumors,
      and mortality in irradiated (IRR) NFPA patients, compared with NFPA patients who
      were not irradiated (non-IRR). DESIGN, SETTING, AND PATIENTS: The study cohort
      included 806 patients with a NFPA from the Dutch National Registry of Growth
      Hormone Treatment in Adults, a nationwide long-term surveillance study in severe
      GH-deficient adult patients. IRR patients (n = 456) were compared with non-IRR
      patients (n = 350). MAIN OUTCOME MEASURES: CVEs, secondary intracranial tumors,
      and mortality were measured. RESULTS: Sixty-nine subjects developed a CVE. In
      men, but not in women, the incidence of a CVE was significantly higher in IRR
      patients than in non-IRR patients (hazard ratio 2.99, 95% confidence interval
      1.31-6.79). A secondary intracranial tumor developed in five IRR patients and two
      non-IRR patients. After adjustment for age, radiotherapy was not associated with
      mortality. CONCLUSIONS: The incidence of secondary intracranial tumors and
      mortality did not differ between IRR and non-IRR patients. However, a CVE was
      found significantly more frequently in IRR men but not in women. Further research
      into the long-term effects of cranial radiotherapy seems mandatory. The potential
      risks of radiotherapy have to be taken into account when radiotherapy is
      considered in NFPA patients, and long-term follow-up is recommended.

PMID- 25574794
TI  - Estimating the effect of palliative care interventions and advance care planning
      on ICU utilization: a systematic review.
AB  - OBJECTIVE: We conducted a systematic review to answer three questions: 1) Do
      advance care planning and palliative care interventions lead to a reduction in
      ICU admissions for adult patients with life-limiting illnesses? 2) Do these
      interventions reduce ICU length of stay? and 3) Is it possible to provide
      estimates of the magnitude of these effects? DATA SOURCES: We searched MEDLINE,
      EMBASE, Cochrane Controlled Clinical Trials, and Cumulative Index to Nursing and
      Allied Health Literature databases from 1995 through March 2014. STUDY SELECTION:
      We included studies that reported controlled trials (randomized and
      nonrandomized) assessing the impact of advance care planning and both primary and
      specialty palliative care interventions on ICU admissions and ICU length of stay
      for critically ill adult patients. DATA EXTRACTION: Nine randomized controlled
      trials and 13 nonrandomized controlled trials were selected from 216 references.
      DATA SYNTHESIS: Nineteen of these studies were used to provide estimates of the
      magnitude of effect of palliative care interventions and advance care planning on
      ICU admission and length of stay. Three studies reporting on ICU admissions
      suggest that advance care planning interventions reduce the relative risk of ICU
      admission for patients at high risk of death by 37% (SD, 23%). For trials
      evaluating palliative care interventions in the ICU setting, we found a 26% (SD,
      23%) relative risk reduction in length of stay with these interventions.
      CONCLUSIONS: Despite wide variation in study type and quality, patients who
      received advance care planning or palliative care interventions consistently
      showed a pattern toward decreased ICU admissions and reduced ICU length of stay.
      Although SDs are wide and study quality varied, the magnitude of the effect is
      possible to estimate and provides a basis for modeling impact on healthcare
      costs.

PMID- 25574795
TI  - Patients' perspectives of enrollment in research without consent: the patients'
      experiences in emergency research-progesterone for the treatment of traumatic
      brain injury study.
AB  - OBJECTIVE: Research in acute illness often requires an exception from informed
      consent. Few studies have assessed the views of patients enrolled in exception
      from informed consent trials. This study was designed to assess the views of
      patients and their surrogates of exception from informed consent enrollment
      within the context of a randomized, placebo-controlled trial of an
      investigational agent for traumatic brain injury. DESIGN: Interactive interview
      study. SETTING: Nested within the Progesterone for the Treatment of Traumatic
      Brain Injury trial, a Phase III randomized controlled trial in acute traumatic
      brain injury. SUBJECTS: Patients and surrogates (for patients incapable of being
      interviewed) enrolled in Progesterone for the Treatment of Traumatic Brain Injury
      under exception from informed consent at 12 sites. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Interviews focused on respondents' acceptance of
      exception from informed consent enrollment in Progesterone for the Treatment of
      Traumatic Brain Injury, use of placebo and randomization, understanding of major
      study elements, and views regarding regulatory protections. Descriptive
      statistical analysis was performed; textual data were analyzed thematically.
      Eighty-five individuals were interviewed. Eighty-four percent had positive
      attitudes toward Progesterone for the Treatment of Traumatic Brain Injury
      inclusion. Seventy-eight percent found their inclusion under exception from
      informed consent acceptable, and 72% found use of exception from informed consent
      in Progesterone for the Treatment of Traumatic Brain Injury acceptable in
      general. Only two respondents clearly disagreed with both personal and general
      exception from informed consent enrollment. The most common concerns (26%)
      related to absence of consent. Eighty percent and 92% were accepting of placebo
      use and randomization, respectively. Although there were few black respondents (n
      = 11), they were less accepting of personal exception from informed consent
      enrollment than white respondents (55% vs 83%; p = 0.0494). CONCLUSIONS:
      Acceptance of exception from informed consent in this placebo-controlled trial of
      an investigational agent was high and exceeded acceptance among community
      consultation participants. Exception from informed consent enrollment appears
      generally consistent with patients' preferences.

PMID- 25574797
TI  - Treadmill Running Reverses Cognitive Declines due to Alzheimer Disease.
AB  - PURPOSE: This study investigated the effect of treadmill running on cognitive
      declines in the early and advanced stages of Alzheimer disease (AD) in 3xTg-AD
      mice. METHODS: At 4 months of age, 3xTg-AD mice (N = 24) were assigned to control
      (AD + CON, n = 12) or exercise (AD + EX, n = 12) group. At 24 months of age, 3xTg
      AD mice (N = 16) were assigned to AD + CON (n = 8) or AD + EX (n = 8) group. The
      AD + EX mice were subjected to treadmill running for 12 wk. At each pathological
      stage, the background strain mice were included as wild-type control (WT + CON, n
      = 8-12). RESULTS: At the early stage of AD, 3xTg-AD mice had impaired short- and
      long-term memory based on Morris water maze along with higher cortical Abeta
      deposition, higher hippocampal and cortical tau pathology, and lower hippocampal
      and cortical PSD-95 and synaptophysin. A 12-wk treadmill running reversed the
      impaired cognitive declines and significantly improved the tau pathology along
      with suppression of the decreased PSD-95 and synaptophysin in the hippocampus and
      cortex. At the advanced stage of AD, 3xTg-AD mice had impaired short- and long
      term memory along with higher levels of Abeta deposition, soluble Abeta1-40 and
      Abeta1-42, tau pathology, and lower levels of brain-derived neurotrophic factor,
      PSD-95, and synaptophysin in the hippocampus and cortex. A 12-wk treadmill
      running reversed the impaired cognitive declines and significantly improved the
      Abeta and tau pathology along with suppression of the decreased synaptic proteins
      and brain-derived neurotrophic factor in the hippocampus and cortex. CONCLUSIONS:
      The current findings suggest that treadmill running provides a nonpharmacological
      means to combat cognitive declines due to AD pathology.

PMID- 25574796
TI  - Energy and Macronutrient Intake in the Midwest Exercise Trial 2 (MET-2).
AB  - PURPOSE: This study aimed to examine the effect of exercise training over 10
      months at two levels of energy expenditure on energy and macronutrient intake in
      a sample of previously sedentary, overweight/obese young adults. METHODS: We
      conducted a 10-month trial in 141 young adults who were randomized to either
      supervised exercise 5 d.wk(-1) at 400 and 600 kcal per session or nonexercise
      control. Participants were instructed to maintain their usual ad libitum diet.
      Energy/macronutrient intake was assessed at baseline and 3.5, 7, and 10 months
      over 7-d periods of ad libitum eating in a university cafeteria using digital
      photography. Foods consumed outside the cafeteria were assessed using multiple
      pass recalls. RESULTS: There were no significant between-group differences in
      absolute energy intake at baseline or at any other time point in the total sample
      or in men. In women, absolute energy intake was significantly greater in the 600
      kcal-per-session group versus controls at both 3.5 and 7 months. There were no
      significant between-group differences in relative energy intake (kcal.kg.d(-1))
      at any time point in the total sample, in men or women. There were no significant
      within- or between-group differences of change in absolute or relative energy
      intake in any of the three study groups in the total sample or in men or women.
      No clinically relevant changes in macronutrient intake were observed.
      CONCLUSIONS: Aerobic exercise training does not significantly alter energy or
      macronutrient intake in overweight and obese young adults. The possibility of a
      threshold level beyond which increased exercise energy expenditure fails to
      produce a more negative energy balance and potential sex differences in the
      energy intake response to increased levels of exercise are potentially important.

PMID- 25574798
TI  - Structural basis for preferential avian receptor binding by the human-infecting
      H10N8 avian influenza virus.
AB  - Since December 2013, at least three cases of human infections with H10N8 avian
      influenza virus have been reported in China, two of them being fatal. To
      investigate the epidemic potential of H10N8 viruses, we examined the receptor
      binding property of the first human isolate, A/Jiangxi-Donghu/346/2013 (JD
      H10N8), and determined the structures of its haemagglutinin (HA) in complex with
      both avian and human receptor analogues. Our results suggest that JD-H10N8
      preferentially binds the avian receptor and that residue R137-localized within
      the receptor-binding site of HA-plays a key role in this preferential binding.
      Compared with the H7N9 avian influenza viruses, JD-H10N8 did not exhibit the
      enhanced binding to human receptors observed with the prevalent H7N9 virus
      isolate Anhui-1, but resembled the receptor binding activity of the early
      outbreak H7N9 isolate (Shanghai-1). We conclude that the H10N8 virus is a typical
      avian influenza virus. 

PMID- 25574800
TI  - Comparison of the Effects of Propofol and Sevoflurane Combined With Remifentanil
      on Transcranial Electric Motor-evoked and Somatosensory-evoked Potential
      Monitoring During Brainstem Surgery.
AB  - BACKGROUND: We compared the effect of propofol and sevoflurane combined with
      remifentanil under comparable bispectral index (BIS) levels on transcranial
      electric motor-evoked potentials (TceMEPs) and somatosensory-evoked potentials
      (SSEPs) during brainstem surgery. MATERIALS AND METHODS: A total of 40
      consecutive patients (20 per group) undergoing brainstem surgery were randomly
      assigned to 2 groups receiving either 0.5 MAC sevoflurane or propofol at an
      effect-site concentration of 2.5 ug/mL for maintenance of anesthesia.
      Remifentanil was administered to both groups at a rate of 0.25 to 0.35 MUg/kg/min
      along with cisatracurium (0.03 to 0.04 mg/kg/h). TceMEP recordings were carried
      out in the abductor pollicis brevis, abductor hallucis, and tibialis anterior
      muscles, whereas cortical SSEPs were measured with posterior tibial nerve
      stimulation. Amplitudes and latencies of TceMEPs and SSEPs were recorded at 1, 2,
      3, and 4 hours after the induction of anesthesia. RESULTS: BIS values remained in
      the 45 to 60 range. Amplitudes of TceMEPs were significantly higher in the
      propofol group than those in the sevoflurane group (P<0.05, at all study time
      points in abductor pollicis brevis and abductor hallucis muscles and only 4 h
      after anesthetic induction for tibialis anterior muscle), whereas latencies were
      shorter in the propofol group than those in the sevoflurane group (P<0.05). No
      differences were observed in latency and amplitude while recording SSEPs between
      the 2 anesthetic techniques. None of the patients had TceMEPs and SSEPs amplitude
      or latency changes, exceeding our set limit. CONCLUSIONS: Both sevoflurane and
      propofol at low dosages combined with remifentanil under comparable BIS values
      and partial muscle relaxation can be used when monitoring of TceMEPs and SSEPs is
      required for brainstem surgery.

PMID- 25574803
TI  - Repeated sprint ability in young basketball players: one vs. two changes of
      direction (Part 2).
AB  - The aim of this study was to compare the training effects based on repeated
      sprint ability (RSA) (with one change of direction) with an intensive repeated
      sprint ability (IRSA) (with two changes of direction) on jump performance and
      aerobic fitness. Eighteen male basketball players were assigned to repeated
      sprint ability and intensive repeated sprint ability training groups (RSAG and
      IRSAG). RSA, IRSA, squat jump (SJ), countermovement jump (CMJ) and Yo-Yo
      intermittent recovery level 1 test were assessed before and after four training
      weeks. The RSA and IRSA trainings consisted of three sets of six sprints (first
      two weeks) and eight sprints (second two weeks) with 4-min sets recovery and 20-s
      of sprints recovery. Four weeks of training led to an overall improvement in most
      of the measures of RSA, but little evidence of any differences between the two
      training modes. Jump performance was enhanced: CMJ of 7.5% (P < 0.0001) and 3.1%
      (P = 0.016) in IRSAG and RSAG respectively. While SJ improved of 5.3% (P = 0.003)
      for IRSAG and 3.4% (P = 0.095) for RSAG. Conversely the Yo-Yo distance increased
      21% (P = 0.301) and 34% (P = 0.017) in IRSAG and RSAG respectively. Therefore,
      short-term repeated sprint training with one/two changes of direction promotes
      improvements in both RSA and IRSA respectively but the better increase on jump
      performance shown a few changes on sprint and endurance performances. 

PMID- 25574801
TI  - Randomized trial of endobronchial ultrasound-guided transbronchial needle
      aspiration under general anesthesia versus moderate sedation.
AB  - RATIONALE: Data about the influence of the type of sedation on yield,
      complications, and tolerance of endobronchial ultrasound-guided transbronchial
      needle aspiration (EBUS-TBNA) are based mostly on retrospective studies and are
      largely inconsistent. OBJECTIVES: To determine whether the type of sedation
      influences the diagnostic yield of EBUS-TBNA, its complication rates, and patient
      tolerance. METHODS: Patients referred for EBUS-TBNA were randomized (1:1) to
      undergo this procedure under general anesthesia (GA) or moderate sedation (MS).
      Pathologists were blinded to group allocation. MEASUREMENTS AND MAIN RESULTS: The
      main outcome was "diagnostic yield," defined as the percentage of patients for
      whom EBUS-TBNA rendered a specific diagnosis. One hundred and forty-nine patients
      underwent EBUS-TBNA, 75 under GA and 74 under MS. Demographic and baseline
      clinical characteristics were well balanced. Two hundred and thirty-six lymph
      nodes (LNs) and six masses were sampled in the GA group (average, 3.2 +/- 1.9
      sites/patient), and 200 LNs and six masses in the MS group (average, 2.8 +/- 1.5
      sites/patient) (P = 0.199). The diagnostic yield was 70.7% (53 of 75) and 68.9%
      (51 of 74) for the GA group and MS group, respectively (P = 0.816). The
      sensitivity was 98.2% in the GA group (confidence interval, 97-100%) and 98.1% in
      the MS group (confidence interval, 97-100%) (P = 0.979). EBUS was completed in
      all patients in the GA group, and in 69 patients (93.3%) in the MS group (P =
      0.028). There were no major complications or escalation of care in either group.
      Minor complications were more common in the MS group (29.6 vs. 5.3%) (P < 0.001).
      Most patients stated they "definitely would" undergo this procedure again in both
      groups (P = 0.355). CONCLUSIONS: EBUS-TBNA performed under MS results in
      comparable diagnostic yield, rate of major complications, and patient tolerance
      as under GA. Future prospective multicenter studies are required to corroborate
      our findings. Clinical trial registered with www.clinicaltrials.gov (NCT
      01430962).

PMID- 25574804
TI  - Total protein concentration and diagnostic test results for gray wolf (Canis
      lupus) serum using Nobuto filter paper strips.
AB  - Nobuto filter paper strips are widely used for storing blood-serum samples, but
      the recovery of proteins from these strips following rehydration is unknown. Poor
      recovery of proteins could reduce the concentration of antibodies and antigens
      and reduce the sensitivity of diagnostic assays. We compared the protein
      concentration, and its association with test sensitivity, of eluted Nobuto strip
      samples with paired sera. We collected and froze serum from five gray wolves
      (Canis lupus) for 8 mo. When thawed, we used a spectrophotometer (absorbance 280
      nm) to determine the serum protein concentration for paired sera and Nobuto
      eluates for each animal in 2-fold serial dilutions. Total protein concentration
      was similar for both sample storage methods (Nobuto eluates and control sera),
      except for the undiluted samples in which Nobuto eluates had higher total protein
      concentrations. Both sample storage methods appear to produce similar results
      using the SNAP(r) 4Dx(r) Test to detect antibodies against pathogens causing Lyme
      disease, anaplasmosis, and ehrlichiosis as well as antigen for canine heartworm
      disease.

PMID- 25574805
TI  - Parasite prevalence and community diversity in sympatric and allopatric
      populations of two woodrat species (Sigmodontinae: Neotoma) in central
      California.
AB  - Patterns of host-parasite association may vary across the landscape in part
      because of host and parasite diversity, divergence, local ecology, or
      interactions among these factors. In central coastal California, we quantified
      parasite prevalence, infection intensity, and diversity in two sister species of
      woodrats (Neotoma fuscipes and Neotoma macrotis) where the species co-occur
      (sympatry) and where each species exists alone (allopatry). In feces from 50
      adults we identified seven taxa: the protozoans Eimeria, Giardia, and
      Cryptosporidium, the nematodes Trichuris, Aspicularis, and Eucoleus, and a
      cestode in the family Anoplocephalidae. Gastrointestinal parasite infection
      intensity and diversity were higher in males than in females, a difference that
      was most pronounced in the more aggressive N. fuscipes. Both species had lower
      infection intensity in sympatry than in allopatry and in sympatry the two species
      did not differ in infection intensity in total but did maintain distinct parasite
      communities. Taken together, our findings suggest that host evolutionary
      differences, including perhaps species-specific patterns of aggressive behavior,
      as well as local ecology, influence the likelihood of infection by these
      endoparasite taxa. 

PMID- 25574807
TI  - A geographic cluster of malignant catarrhal fever in moose (Alces alces) in
      Norway.
AB  - Three cases of lethal sheep-associated malignant catarrhal fever (SA-MCF) in free
      ranging moose (Alces alces) were diagnosed in Lesja, Norway, December 2008
      February 2010. The diagnosis was based on PCR identification of ovine herpesvirus
      2 (OvHV-2) DNA (n = 3) and typical histopathologic lesions (n = 1). To study the
      possibility of subclinical or latent MCF virus (MCFV) infection in this moose
      population and in red deer (Cervus elaphus), we examined clinically normal
      animals sampled during hunting in Lesja 2010 by serology and PCR. Sera from 63
      moose and 33 red deer were tested for antibodies against MCFV by competitive
      inhibition enzyme-linked immunosorbent assay. To test for MCFVs, a consensus PCR
      for herpesviral DNA was run on spleen samples from 23 moose and 17 red deer. All
      samples were antibody and PCR negative. Thus, there is no evidence of previous
      exposure, subclinical infection, or latent infection in this sample. This
      seasonal cluster of SA-MCF cases (2008-10) may be attributable to exposure of
      moose to lambs when OvHV-2 shedding is presumed to be maximal, compounded by an
      unusual extended grazing period by sheep in the autumn. 

PMID- 25574806
TI  - A Mycoplasma species of Emydidae turtles in the northeastern USA.
AB  - Mycoplasma infections can cause significant morbidity and mortality in captive
      and wild chelonians. As part of a health assessment of endangered bog turtles
      (Glyptemys muhlenbergii) in the northeastern US, choanal and cloacal swabs from
      these and other sympatric species, including spotted turtles (Clemmys guttata),
      eastern box turtles (Terrapene carolina carolina), wood turtles (Glyptemys
      insculpta), and common snapping turtles (Chelydra serpentina) from 10 sampling
      sites in the states (US) of Delaware, New Jersey, and Pennsylvania, were tested
      by PCR for Mycoplasma. Of 108 turtles tested, 63 (58.3%) were PCR positive for
      Mycoplasma including 58 of 83 bog turtles (70%), three of three (100%) eastern
      box turtles, and two of 11 (18%) spotted turtles; all snapping turtles (n = 7)
      and wood turtles (n = 4) were negative. Sequence analysis of portions of the 16S
      23S intergenic spacer region and the 16S ribosomal RNA gene revealed a single,
      unclassified species of Mycoplasma that has been previously reported in eastern
      box turtles, ornate box turtles (Terrapene ornata ornata), western pond turtles
      (Emys marmorata), and red-eared sliders (Trachemys scripta elegans). We document
      a high incidence of Mycoplasma, in the absence of clinical disease, in wild
      emydid turtles. These findings, along with wide distribution of the identified
      Mycoplasma sp. across a broad geographic region, suggest this bacterium is likely
      a commensal inhabitant of bog turtles, and possibly other species of emydid
      turtles, in the northeastern US. 

PMID- 25574808
TI  - Risk factors for Toxoplasma gondii exposure in semiaquatic mammals in a
      freshwater ecosystem.
AB  - We assessed risk factors for Toxoplasma gondii exposure in semiaquatic mammals in
      east-central Illinois, US. This agricultural region has extensive drainage
      systems that could potentially transport T. gondii oocysts into the watershed. We
      used muskrats (Ondatra zibethicus) and American mink (Neovison vison) as
      sentinels of watershed contamination. We predicted individuals from larger
      subwatersheds would more likely be antibody-positive for T. gondii, as they were
      exposed to drainage from larger areas. We also evaluated amount of urban land
      cover within the subwatershed, proximity to farmsteads, and age of individuals in
      competing models of T. gondii infection. Antibodies to T. gondii were assayed in
      animal sera by modified agglutination tests (titer 25 or higher) and detected in
      18 (60%) of 30 muskrats and 20 (77%) of 26 mink. Infection rates were >=1.7 times
      higher than those typical for mammals in upland habitats in this region.
      Subwatershed size and age class were important predictors of T. gondii infection
      in muskrats (R(2) = 0.35). Models incorporating urban land cover and proximity to
      farmsteads had little support. None of our models of antibody prevalence in mink
      were well supported, possibly because mink are less strictly associated with
      riparian habitats. Because ~91% of our study area is devoted to agricultural
      production and urbanization, transport of T. gondii into freshwater ecosystems is
      likely facilitated by modified drainage practices common in these areas. 

PMID- 25574810
TI  - Enhanced Moran effect by spatial variation in environmental autocorrelation.
AB  - Spatial correlations in environmental stochasticity can synchronize populations
      over wide areas, a phenomenon known as the Moran effect. The Moran effect has
      been confirmed in field, laboratory and theoretical investigations. Little is
      known, however, about the Moran effect in a common ecological case, when
      environmental variation is temporally autocorrelated and this autocorrelation
      varies spatially. Here we perform chemostat experiments to investigate the
      temporal response of independent phytoplankton populations to autocorrelated
      stochastic forcing. In contrast to naive expectation, two populations without
      direct coupling can be more strongly correlated than their environmental forcing
      (enhanced Moran effect), if the stochastic variations differ in their
      autocorrelation. Our experimental findings are in agreement with numerical
      simulations and analytical calculations. The enhanced Moran effect is robust to
      changes in population dynamics, noise spectra and different measures of
      correlation-suggesting that noise-induced synchrony may play a larger role for
      population dynamics than previously thought.

PMID- 25574811
TI  - Creating the health care team of the future: the toronto model for
      interprofessional education and practice.

PMID- 25574812
TI  - H2O2-activatable and O2-evolving nanoparticles for highly efficient and selective
      photodynamic therapy against hypoxic tumor cells.
AB  - The low selectivity of currently available photosensitizers, which causes the
      treatment-related toxicity and side effects on adjacent normal tissues, is a
      major limitation for clinical photodynamic therapy (PDT) against cancer.
      Moreover, since PDT process is strongly oxygen dependent, its therapeutic effect
      is seriously hindered in hypoxic tumor cells. To overcome these problems, a cell
      specific, H(2)O(2)-activatable, and O(2)-evolving PDT nanoparticle (HAOP NP) is
      developed for highly selective and efficient cancer treatment. The nanoparticle
      is composed of photosensitizer and catalase in the aqueous core, black hole
      quencher in the polymeric shell, and functionalized with a tumor targeting ligand
      c(RGDfK). Once HAOP NP is selectively taken up by alpha(v)beta(3) integrin-rich
      tumor cells, the intracellular H(2)O(2) penetrates the shell into the core and is
      catalyzed by catalase to generate O(2), leading to the shell rupture and release
      of photosensitizer. Under irradiation, the released photosensitizer induces the
      formation of cytotoxic singlet oxygen ((1)O(2)) in the presence of O(2) to kill
      cancer cells. The cell-specific and H(2)O(2)-activatable generation of (1)O(2)
      selectively destroys cancer cells and prevents the damage to normal cells. More
      significantly, HAOP NP continuously generates O(2) in PDT process, which greatly
      improves the PDT efficacy in hypoxic tumor. Therefore, this work presents a new
      paradigm for H(2)O(2)-triggered PDT against cancer cells and provides a new
      avenue for overcoming hypoxia to achieve effective treatment of solid tumors.

PMID- 25574809
TI  - Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem
      cells/progenitors through endothelial AT2R and cytoskeletal dysregulation.
AB  - Patients with organ failure of vascular origin have increased circulating
      haematopoietic stem cells and progenitors (HSC/P). Plasma levels of angiotensin
      II (Ang-II), are commonly increased in vasculopathies. Hyperangiotensinemia
      results in activation of a very distinct Ang-II receptor set, Rho family GTPase
      members, and actin in bone marrow endothelial cells (BMEC) and HSC/P, which
      results in decreased membrane integrin activation in both BMEC and HSC/P, and in
      HSC/P de-adhesion and mobilization. The Ang-II effect can be reversed
      pharmacologically and genetically by inhibiting Ang-II production or signalling
      through BMEC AT2R, HSCP Ang-II receptor type 1 (AT1R)/AT2R or HSC/P RhoA, but not
      by interfering with other vascular tone mediators. Hyperangiotensinemia and high
      counts of circulating HSC/P seen in sickle cell disease (SCD) as a result of
      vascular damage, is significantly decreased by Ang-II inhibitors. Our data define
      for the first time the role of Ang-II HSC/P traffic regulation and redefine the
      haematopoietic consequences of anti-angiotensin therapy in SCD. 

PMID- 25574813
TI  - Extrusion and Extruded Products: Changes in Quality Attributes as Affected by
      Extrusion Process Parameters: A Review.
AB  - Extrusion of foods is an emerging technology for the food industries to process
      and market a large number of products of varying size, shape, texture, and taste.
      Extrusion cooking technology has led to production of wide variety of products
      like pasta, breakfast cereals, bread crumbs, biscuits, crackers, croutons, baby
      foods, snack foods, confectionery items, chewing gum, texturized vegetable
      protein (TVP), modified starch, pet foods, dried soups, dry beverage mixes etc.
      The functional properties of extruded foods plays an important role for their
      acceptability which include water absorption, water solubility, oil absorption
      indexes, expansion index, bulk density and viscosity of the dough. The aim of
      this review is to give the detailed outlines about the potential of extrusion
      technology in development of different types of products and the role of
      extrusion-operating conditions and their effect on product development resulting
      in quality changes i.e physical, chemical, and nutritional, experienced during
      the extrusion process. 

PMID- 25574814
TI  - Assessment of a Monte-Carlo simulation of SPECT recordings from a new-generation
      heart-centric semiconductor camera: from point sources to human images.
AB  - Geant4 application for tomographic emission (GATE), a Monte-Carlo simulation
      platform, has previously been used for optimizing tomoscintigraphic images
      recorded with scintillation Anger cameras but not with the new-generation heart
      centric cadmium-zinc-telluride (CZT) cameras. Using the GATE platform, this study
      aimed at simulating the SPECT recordings from one of these new CZT cameras and to
      assess this simulation by direct comparison between simulated and actual recorded
      data, ranging from point sources to human images. Geometry and movement of
      detectors, as well as their respective energy responses, were modeled for the CZT
      'D.SPECT' camera in the GATE platform. Both simulated and actual recorded data
      were obtained from: (1) point and linear sources of (99m)Tc for compared
      assessments of detection sensitivity and spatial resolution, (2) a cardiac insert
      filled with a (99m)Tc solution for compared assessments of contrast-to-noise
      ratio and sharpness of myocardial borders and (3) in a patient with myocardial
      infarction using segmented cardiac magnetic resonance imaging images. Most of the
      data from the simulated images exhibited high concordance with the results of
      actual images with relative differences of only: (1) 0.5% for detection
      sensitivity, (2) 6.7% for spatial resolution, (3) 2.6% for contrast-to-noise
      ratio and 5.0% for sharpness index on the cardiac insert placed in a diffusing
      environment. There was also good concordance between actual and simulated gated
      SPECT patient images for the delineation of the myocardial infarction area,
      although the quality of the simulated images was clearly superior with increases
      around 50% for both contrast-to-noise ratio and sharpness index. SPECT recordings
      from a new heart-centric CZT camera can be simulated with the GATE software with
      high concordance relative to the actual physical properties of this camera. These
      simulations may be conducted up to the stage of human SPECT-images even if
      further refinement is needed in this setting. 

PMID- 25574815
TI  - Health information-seeking behavior of seniors who use the Internet: a survey.
AB  - BACKGROUND: The Internet is viewed as an important source for health information
      and a medium for patient empowerment. However, little is known about how seniors
      use the Internet in relation to other sources for health information. OBJECTIVE:
      The aim was to determine which information resources seniors who use the Internet
      use and trust for health information, which sources are preferred, and which
      sources are used by seniors for different information needs. METHODS: Questions
      from published surveys were selected based on their relevance to the study
      objectives. The Autonomy Preference Index was used to assess information needs
      and preferences for involvement in health decisions. Invitation to participate in
      this online survey was sent to the email list of a local senior organization (298
      addresses) in the Netherlands. RESULTS: There were 118 respondents with a median
      age of 72 years (IQR 67-78 years). Health professionals, pharmacists, and the
      Internet were the most commonly used and trusted sources of health information.
      Leaflets, television, newspapers, and health magazines were also important
      sources. Respondents who reported higher use of the Internet also reported higher
      use of other sources (P<.001). Use of health professionals, pharmacists,
      leaflets, telephone, television, and radio were not significantly different; use
      of all other resources was significantly higher in frequent Internet users. When
      in need of health information, preferred sources were the Internet (46/105,
      43.8%), other sources (eg, magazines 38/105, 36.2%), health professionals
      (18/105, 17.1%), and no information seeking (3/105, 2.8%). Of the 51/107
      respondents who indicated that they had sought health information in the last 12
      months, 43 sought it after an appointment, 23 were preparing for an appointment,
      and 20 were deciding if an appointment was needed. The source used varied by the
      type of information sought. The Internet was used most often for symptoms (27/42,
      64%), prognosis (21/31, 68%), and treatment options (23/41, 62%), whereas health
      professionals were asked for additional information on medications (20/36, 56%),
      side effects (17/36, 47%), coping (17/31, 55%), practical care (12/14, 86%), and
      nutrition/exercise (18/30, 60%). CONCLUSIONS: For these seniors who use the
      Internet, the Internet was a preferred source of health information. Seniors who
      report higher use of the Internet also report higher use of other information
      resources and were also the primary consumers of paper-based resources.
      Respondents most frequently searched for health information after an appointment
      rather than to prepare for an appointment. Resources used varied by health topic.
      Future research should seek to confirm these findings in a general elderly
      population, investigate how seniors seek and understand information on the
      Internet, and investigate how to reach seniors who prefer not to use the Internet
      for health information.

PMID- 25574817
TI  - The role of visible and infrared spectroscopy combined with chemometrics to
      measure phenolic compounds in grape and wine samples.
AB  - The content of phenolic compounds determines the state of phenolic ripening of
      red grapes, which is a key criterion in setting the harvest date to produce
      quality red wines. Wine phenolics are also important quality components that
      contribute to the color, taste, and mouth feel of wines. Spectroscopic techniques
      (e.g., near and mid infrared) offer the potential to simplify and reduce the
      analytical time for a range of grape and wine analytes. It is this
      characteristic, together with the ability to simultaneously measure several
      analytes in the same sample at the same time, which makes these techniques very
      attractive for use in both industry and research. The objective of this mini
      review is to present examples and to discuss different applications of visible
      (VIS), near infrared (NIR) and mid infrared (MIR) to assess and measure phenolic
      compounds in grape and wines. 

PMID- 25574816
TI  - Phosphohistidine phosphatase 1 (PHPT1) also dephosphorylates phospholysine of
      chemically phosphorylated histone H1 and polylysine.
AB  - BACKGROUND: Phosphohistidine phosphatase 1 (PHPT1), also named protein histidine
      phosphatase (PHP), is a eukaryotic enzyme dephosphorylating proteins and peptides
      that are phosphorylated on a histidine residue. A preliminary finding that
      histone H1, which lacks histidine, was phosphorylated by phosphoramidate and
      dephosphorylated by PHPT1 prompted the present investigation. METHODS: Histone H1
      and polylysine were phosphorylated at a low concentration (3.9 mM) of
      phosphoramidate. Their dephosphorylation by recombinant human PHPT1 was
      investigated by using a DEAE-Sepharose spin column technique earlier developed by
      us for studies on basic phosphoproteins and phosphopeptides. Determination of
      protein-bound, acid-labile phosphate was performed by a malachite green method.
      Mass spectrometry (MS) was used to investigate the occurrence of N-epsilon
      phospholysine residues in a phosphorylated histone H1.2 preparation, and to
      measure the activity of PHPT1 against free N-omega-phosphoarginine. RESULTS:
      Histone H1.2, which lacks histidine, was phosphorylated by phosphoramidate on
      several lysine residues, as shown by MS. PHPT1 was shown to dephosphorylate
      phosphohistone H1 at a rate similar to that previously described for the
      dephosphorylation of phosphohistidine-containing peptides. In addition,
      phosphopolylysine was an equally good substrate for PHPT1. However, no
      dephosphorylation of free phosphoarginine by PHPT1 could be detected. CONCLUSION:
      The finding that PHPT1 can dephosphorylate phospholysine in chemically
      phosphorylated histone H1 and polylysine demonstrates a broader specificity for
      this enzyme than known so far.

PMID- 25574818
TI  - On the antimicrobial activity of various peptide-based dendrimers of similar
      architecture.
AB  - Antimicrobial drug resistance is a major human health threat. Among the many
      attempts to tackle this problem, the synthesis of antimicrobial compounds that
      mimic natural antimicrobial peptides appears as a promising approach. Peptide
      based dendrimers can be designed to have higher potency than natural
      antimicrobial peptides and at the same time they can evade the bacterial defense
      system. Novel dendrimers with similar chemical structure but varying potency in
      terms of minimum inhibitory concentration were designed. The dependency between
      dendrimer structure and antibacterial activity as well as their capacity to
      attack model cell membranes was studied. The data suggests that supramolecular
      structure in terms of charge distribution and amphiphilicity, rather than net
      charge, is the main driver for disruption of cellular membranes and this
      correlates well with dendrimer hemolytic activity. 

PMID- 25574819
TI  - Pharmacological profile of xanthohumol, a prenylated flavonoid from hops (Humulus
      lupulus).
AB  - The female inflorescences of hops (Humulus lupulus L.), a well-known bittering
      agent used in the brewing industry, have long been used in traditional medicines.
      Xanthohumol (XN) is one of the bioactive substances contributing to its medical
      applications. Among foodstuffs XN is found primarily in beer and its natural
      occurrence is surveyed. In recent years, XN has received much attention for its
      biological effects. The present review describes the pharmacological aspects of
      XN and summarizes the most interesting findings obtained in the preclinical
      research related to this compound, including the pharmacological activity, the
      pharmacokinetics, and the safety of XN. Furthermore, the potential use of XN as a
      food additive considering its many positive biological effects is discussed. 

PMID- 25574820
TI  - A novel one-pot green synthesis of dispirooxindolo-pyrrolidines via 1,3-dipolar
      cycloaddition reactions of azomethine ylides.
AB  - A facile synthesis of dispirooxindolopyrrolidines has been accomplished via a one
      pot three component 1,3-dipolar cycloaddition reaction. The reaction of
      azomethine ylides generated in situ from L-phenylalanine and substituted isatins
      with a series of unusual (E)-2-oxoindolino-3-ylidene acetophenone dipolarophiles
      in the ionic liquid 1-butyl-3-methylimidazolium bromide [bmim]BF4, furnished the
      cycloadducts in good yields, with the regioisomers 5a-f being obtained with high
      selectivity. Furthermore, the recyclability of [bmim]BF4, up to five times, was
      also investigated. 

PMID- 25574822
TI  - Design, synthesis and anti-tobacco mosaic virus (TMV) activity of 5-chloro-N-(4
      cyano-1-aryl-1H-pyrazol-5-yl)-1-aryl-3-methyl-1H-pyrazole-4-carboxamide
      derivatives.
AB  - A series of novel pyrazole amide derivatives 3a-3p which take TMV PC protein as
      the target has been designed and synthesized by the reactions of 5-chloro-1-aryl
      3-methyl-1H-pyrazole-4-carboxylic acids with 5-amino-1-aryl-1H-pyrazole-4
      carbonitriles. All the compounds were characterized by 1H-NMR, mass spectroscopy
      and elemental analysis. Preliminary bioassays indicated that all the compounds
      acted against the tobacco mosaic virus (TMV) with different in vivo and in vitro
      modes at 500 MUg/mL and were found to possess promising activity. Especially,
      compound 3p showed the most potent biological activity against tobacco mosaic
      virus (TMV) compared to ningnanmycin, and a molecular docking study was performed
      and the binding model revealed that the pyrazole amide moiety was tightly
      embedded in the binding sites of TMV PC (PDB code: 2OM3). 

PMID- 25574823
TI  - Synthesis of some new Thieno[2,3-b]pyridines, Pyrimidino[4',5':4,5]thieno[2,3
      b]pyridine and Pyridines Incorporating 5-Bromobenzofuran-2-yl Moiety.
AB  - 2-Sulfanyl-6-(2-thienyl)pyridine-3-carbonitrile, 1-Amino-6-(5-bromo-benzofuran-2
      yl)-2-oxo-1,2-dihydro-pyridine-3-carbonitrile, thieno[2,3-b]pyridins,
      pyrimidino[4',5':4,5] thieno[2,3-b]pyridine, quinazoline and carbamate
      derivatives were synthesized from sodium 3-(5-bromobenzofuran-2-yl)-3-oxoprop-1
      en-1-olate with. The newly synthesized compounds were elucidated by elemental
      analysis, spectral data, and alternative synthesis whenever possible and chemical
      transportation. 

PMID- 25574821
TI  - Pinelliae rhizoma, a toxic chinese herb, can significantly inhibit CYP3A activity
      in rats.
AB  - Raw Pinelliae Rhizoma (RPR) is a representative toxic herb that is widely used
      for eliminating phlegm or treating cough and vomiting. Given its irritant
      toxicity, its processed products, including Pinelliae Rhizoma Praeparatum (PRP)
      and Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRPZA), are more
      commonly applied and administered concomitantly with other chemical drugs, such
      as cough medications. This study aimed to investigate the effects of RPR, PRP,
      and PRPZA on CYP3A activity. Testosterone (Tes) and buspirone (BP) were used as
      specific probe substrates ex vivo and in vivo, respectively. CYP3A activity was
      determined by the metabolite formation ratios from the substrates. Ex vivo
      results show that the metabolite formation ratios from Tes significantly
      decreased, indicating that RPR, PRP, and PRPZA could inhibit CYP3A activity in
      rats. CYP3A protein and mRNA levels were determined to explore the underlying
      mechanism. These levels showed marked and consistent down-regulation with CYP3A
      activity. A significant decrease in metabolite formation ratios from BP was also
      found in PRPZA group in vivo, implying that PRPZA could inhibit CYP3A activity.
      Conclusively, co-administration of PR with other CYP3A-metabolizing drugs may
      cause drug-drug interactions. Clinical use of PR-related formulae should be
      monitored carefully to avoid adverse interactions. 

PMID- 25574824
TI  - Isoleojaponin, a new Halimane diterpene isolated from Leonurus japonicus.
AB  - Leojaponin (2), a labdane diterpene, was isolated from the EtOH extract of the
      herb of Leonurus japonicus together with a new halimane diterpene named
      isoleojaponin (1). Isoleojaponin has a new diterpene skeleton with a unique cross
      conjugated alpha,beta-unsaturated ketone system, Their structures were elucidated
      by physical and spectroscopic analysis, and the relative configuration of the
      chiral C-9 carbon was determined by a computational method, and analysis of its
      possible biogenesis pathways. 

PMID- 25574830
TI  - Controllable and stepwise synthesis of soluble ladder-conjugated bis(perylene
      imide) fluorenebisimidazole as a multifunctional optoelectronic material.
AB  - By a controllable and stepwise strategy, a soluble ladder-conjugated perylene
      derivative BPI-FBI as the only product has been synthesized, which avoids the
      tough work to isolate regioisomers generated by a conventional one-step
      condensation method. BPI-FBI exhibits broad absorption spectra covering the whole
      visible region from 300 to 700 nm because of the large pi-conjugation skeleton
      and has a low LUMO level inheriting the prototype PDI. In the steady-state space
      charge-limited current (SCLC) devices, BPI-FBI exhibits an intrinsic electron
      mobility of 1.01 * 10(-5) cm(2) V(-1) s(-1). With a high two photon absorbing
      activity in the near-infrared region from 1200 to 1400 nm, BPI-FBI also exhibits
      good optical limiting performance, which will be useful for sensor or human eye
      protection and stabilization of light sources for optical communications. 

PMID- 25574831
TI  - Influence of non-covalent modification of multiwalled carbon nanotubes on the
      crystallization behaviour of binary blends of polypropylene and polyamide 6.
AB  - Blends of polypropylene (PP) and polyamide 6 (PA6) with multiwalled carbon
      nanotubes (MWNTs) were prepared using different processing strategies in a twin
      screw micro-compounder. The effect of MWNTs on the crystallization behaviour of
      the PP phase and the PA6 phase of the blend has been investigated through non
      isothermal crystallization studies by differential scanning calorimetric
      analysis. Furthermore, the effect of the addition of the compatibilizer (PP-g-MA)
      and the modification of MWNTs (m-MWNTs) with a non-covalent organic modifier (Li
      salt of 6 amino hexanoic acid, Li-AHA) has also been studied in context to the
      crystallization behaviour of the PP and PA6 phase in the blend. The
      crystallization studies have indicated a significant increase in bulk
      crystallization temperature of the PP phase in the blend in the presence of
      MWNTs. Moreover, the formation of 'trans-lamellar crystalline' structure
      consisting of PA6 'trans-crystalline lamellae' on MWNTs surface was facilitated
      in the case of blends prepared via 'protocol 2' as compared to the corresponding
      blends prepared via 'protocol 1'. Wide angle X-ray diffraction analysis has
      showed the existence of a beta-polymorph of the PP phase due to incorporation of
      the PA6 phase in the blend. Addition of MWNTs in the blends has facilitated
      further beta-crystalline structure formation of the PP phase. In the presence of
      m-MWNTs, a higher beta-fraction was observed in the PP phase as compared to the
      blend with pristine MWNTs. Addition of PP-g-MA has suppressed the beta-phase
      formation in the PP phase in the blend. X-ray bulk texture analysis revealed that
      incorporation of PA6 as well as pristine/modified MWNTs has influenced the extent
      of orientation of the PP chains towards specific crystalline planes in various
      blend compositions of PP and PA6. 

PMID- 25574832
TI  - Synthesis of 4-substituted oxazolo[4,5-c]quinolines by direct reaction at the C-4
      position of oxazoles.
AB  - A facile synthesis of 4-aryl substituted oxazolo[4,5-c]quinolines has been
      described via a modified Pictet-Spengler method and using Cu(TFA)2 as a catalyst.
      The developed methodology directly functionalizes the C-4 position of oxazoles
      without the aid of any prefunctionalization, in the presence of the more reactive
      C-2 position in good yields. The versatility of the established method has been
      demonstrated by its application in the synthesis of 4-substituted oxazolo
      [1,8]naphthyridine ring systems. 

PMID- 25574826
TI  - CODAS syndrome is associated with mutations of LONP1, encoding mitochondrial AAA+
      Lon protease.
AB  - CODAS syndrome is a multi-system developmental disorder characterized by
      cerebral, ocular, dental, auricular, and skeletal anomalies. Using whole-exome
      and Sanger sequencing, we identified four LONP1 mutations inherited as homozygous
      or compound-heterozygous combinations among ten individuals with CODAS syndrome.
      The individuals come from three different ancestral backgrounds (Amish-Swiss from
      United States, n = 8; Mennonite-German from Canada, n = 1; mixed European from
      Canada, n = 1). LONP1 encodes Lon protease, a homohexameric enzyme that mediates
      protein quality control, respiratory-complex assembly, gene expression, and
      stress responses in mitochondria. All four pathogenic amino acid substitutions
      cluster within the AAA(+) domain at residues near the ATP-binding pocket. In
      biochemical assays, pathogenic Lon proteins show substrate-specific defects in
      ATP-dependent proteolysis. When expressed recombinantly in cells, all altered Lon
      proteins localize to mitochondria. The Old Order Amish Lon variant (LONP1
      c.2161C>G[p.Arg721Gly]) homo-oligomerizes poorly in vitro. Lymphoblastoid cell
      lines generated from affected children have (1) swollen mitochondria with
      electron-dense inclusions and abnormal inner-membrane morphology; (2) aggregated
      MT-CO2, the mtDNA-encoded subunit II of cytochrome c oxidase; and (3) reduced
      spare respiratory capacity, leading to impaired mitochondrial proteostasis and
      function. CODAS syndrome is a distinct, autosomal-recessive, developmental
      disorder associated with dysfunction of the mitochondrial Lon protease. 

PMID- 25574825
TI  - Genome-wide comparative analysis of atopic dermatitis and psoriasis gives insight
      into opposing genetic mechanisms.
AB  - Atopic dermatitis and psoriasis are the two most common immune-mediated
      inflammatory disorders affecting the skin. Genome-wide studies demonstrate a high
      degree of genetic overlap, but these diseases have mutually exclusive clinical
      phenotypes and opposing immune mechanisms. Despite their prevalence, atopic
      dermatitis and psoriasis very rarely co-occur within one individual. By utilizing
      genome-wide association study and ImmunoChip data from >19,000 individuals and
      methodologies developed from meta-analysis, we have identified opposing risk
      alleles at shared loci as well as independent disease-specific loci within the
      epidermal differentiation complex (chromosome 1q21.3), the Th2 locus control
      region (chromosome 5q31.1), and the major histocompatibility complex (chromosome
      6p21-22). We further identified previously unreported pleiotropic alleles with
      opposing effects on atopic dermatitis and psoriasis risk in PRKRA and
      ANXA6/TNIP1. In contrast, there was no evidence for shared loci with effects
      operating in the same direction on both diseases. Our results show that atopic
      dermatitis and psoriasis have distinct genetic mechanisms with opposing effects
      in shared pathways influencing epidermal differentiation and immune response. The
      statistical analysis methods developed in the conduct of this study have produced
      additional insight from previously published data sets. The approach is likely to
      be applicable to the investigation of the genetic basis of other complex traits
      with overlapping and distinct clinical features. 

PMID- 25574833
TI  - Fluorescence in two-photon-excited diffusible samples exposed to photobleaching:
      a simulation-based study.
AB  - We created a simulation model to investigate the characteristics of fluorescence
      in two-photon-excited samples. In the model, the sample is a diffusible solution
      of fluorophore molecules, which is divided into cubic cells and illuminated by a
      train of focused laser pulses described as a Gaussian beam. Simulating the state
      transitions according to a multilevel photodynamic model (also including
      photobleaching and intersystem crossing), the simulator provides the expected
      number and the spatial distribution of emitted photons over time. Our simulations
      demonstrated how the illumination laser power, diffusion, and the photodynamic
      parameters of the fluorophore affect fluorescence. We revealed the unusual
      fluorescent profile that evolves as photobleaching progresses: the most photons
      are not emitted from the focus (where a "dark hole" appears) but from an
      ellipsoid around the focus. The model could be adapted to several fluorescent
      techniques (such as two-photon microscopy and fluorescence recovery after
      photobleaching). Furthermore, it might help to optimize the operating parameters
      of the measurement devices (e.g., in order to reach higher image quality and
      lower photobleaching).

PMID- 25574827
TI  - HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy.
AB  - Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so
      strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(*)01:02
      DQB1(*)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known
      triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting
      autoimmunity triggered by upper-airway infections. Additional effects of other
      HLA-DQ alleles have been reported consistently across multiple ethnic groups.
      Using over 3,000 case and 10,000 control individuals of European and Chinese
      background, we examined the effects of other HLA loci. After careful matching of
      HLA-DR and HLA-DQ in case and control individuals, we found strong protective
      effects of HLA-DPA1(*)01:03-DPB1(*)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38
      0.67], p = 1.01 * 10(-6)) and HLA-DPA1(*)01:03-DPB1(*)04:01 (DP0401; OR = 0.61
      [0.47-0.80], p = 2.07 * 10(-4)) and predisposing effects of HLA-DPB1(*)05:01 in
      Asians (OR = 1.76 [1.34-2.31], p = 4.71 * 10(-05)). Similar effects were found by
      conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45
      [0.38-0.55] p = 8.99 * 10(-17)) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 * 10(
      5)). HLA-class-II-independent associations with HLA-A(*)11:01 (OR = 1.32 [1.13
      1.54], p = 4.92 * 10(-4)), HLA-B(*)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 * 10(
      5)), and HLA-B(*)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 * 10(-5)) were also seen
      across ethnic groups in the HLA class I region. These effects might reflect
      modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles
      on response to viral infections such as that of influenza. 

PMID- 25574834
TI  - An easy-to-detect nona-arginine peptide for epidermal targeting.
AB  - A correlative approach combining synchrotron radiation based IR microscopy and
      fluorescence microscopy enabled the successful detection and quantification of a
      nona-arginine peptide labelled with a Single Core Multimodal Probe for Imaging
      (SCoMPI) in skin biopsies. The topical penetration of the conjugate appeared to
      be time dependent and occurred most probably via the extracellular matrix. 

PMID- 25574835
TI  - Calcium phosphate flocs and the clarification of sugar cane juice from whole of
      crop harvesting.
AB  - Sugar cane biomass is one of the most viable feedstocks for the production of
      renewable fuels and chemicals. Therefore, processing the whole of crop (WC)
      (i.e., stalk and trash, instead of stalk only) will increase the amount of
      available biomass for this purpose. However, effective clarification of juice
      expressed from WC for raw sugar manufacture is a major challenge because of the
      amounts and types of non-sucrose impurities (e.g., polysaccharides, inorganics,
      proteins, etc.) present. Calcium phosphate flocs are important during sugar cane
      juice clarification because they are responsible for the removal of impurities.
      Therefore, to gain a better understanding of the role of calcium phosphate flocs
      during the juice clarification process, the effects of impurities on the
      physicochemical properties of calcium phosphate flocs were examined using small
      angle laser light scattering technique, attenuated total reflectance Fourier
      transformed infrared spectroscopy, and X-ray powder diffraction. Results on
      synthetic sugar juice solutions showed that the presence of SiO2 and Na(+) ions
      affected floc size and floc structure. Starch and phosphate ions did not affect
      the floc structure; however, the former reduced the floc size, whereas the latter
      increased the floc size. The study revealed that high levels of Na(+) ions would
      negatively affect the clarification process the most, as they would reduce the
      amount of suspended particles trapped by the flocs. A complementary study on
      prepared WC juice using cold and cold/intermediate liming techniques was
      conducted. The study demonstrated that, in comparison to the one-stage (i.e.,
      conventional) clarification process, a two-stage clarification process using cold
      liming removed more polysaccharides (<=19%), proteins (<=82%), phosphorus
      (<=53%), and SiO2 (<=23%) in WC juice but increased Ca(2+) (<=136%) and sulfur
      (<=200%).

PMID- 25574836
TI  - Immobilization of carboxymethylated polyethylenimine-metal-ion complexes in
      porous membranes to selectively capture his-tagged protein.
AB  - Membrane adsorbers rapidly capture tagged proteins because flow through membrane
      pores efficiently conveys proteins to binding sites. Effective adsorbers,
      however, require membrane pores coated with thin films that bind multilayers of
      proteins. This work employs adsorption of polyelectrolytes that chelate metal
      ions to create functionalized membranes that selectively capture polyhistidine
      tagged (His-tagged) proteins with binding capacities equal to those of high
      binding commercial beads. Adsorption of functional polyelectrolytes is simpler
      than previous membrane-modification strategies such as growth of polymer brushes
      or derivatization of adsorbed layers with chelating moieties. Sequential
      adsorption of protonated poly(allylamine) (PAH) and carboxymethylated branched
      polyethylenimine (CMPEI) leads to membranes that bind Ni(2+) and capture ~60 mg
      of His-tagged ubiquitin per mL of membrane. Moreover, these membranes enable
      isolation of His-tagged protein from cell lysates in <15 min. The backbone amine
      groups in CMPEI likely increase swelling in water to double protein binding
      compared to films composed of PAH and the chelating polymer poly[(N,N
      dicarboxymethyl)allylamine] (PDCMAA), which has a hydrocarbon backbone. Metal
      leaching from PAH/CMPEI- and PAH/PDCMAA-modified membranes is similar to that
      from GE Hitrap FF columns. Eluates with 0.5 M imidazole contain <10 ppm of
      Ni(2+). 

PMID- 25574837
TI  - HIF2alpha signaling inhibits adherens junctional disruption in acute lung injury.
AB  - Vascular endothelial barrier dysfunction underlies diseases such as acute
      respiratory distress syndrome (ARDS), characterized by edema and inflammatory
      cell infiltration. The transcription factor HIF2alpha is highly expressed in
      vascular endothelial cells (ECs) and may regulate endothelial barrier function.
      Here, we analyzed promoter sequences of genes encoding proteins that regulate
      adherens junction (AJ) integrity and determined that vascular endothelial protein
      tyrosine phosphatase (VE-PTP) is a HIF2alpha target. HIF2alpha-induced VE-PTP
      expression enhanced dephosphorylation of VE-cadherin, which reduced VE-cadherin
      endocytosis and thereby augmented AJ integrity and endothelial barrier function.
      Mice harboring an EC-specific deletion of Hif2a exhibited decreased VE-PTP
      expression and increased VE-cadherin phosphorylation, resulting in defective AJs.
      Mice lacking HIF2alpha in ECs had increased lung vascular permeability and water
      content, both of which were further exacerbated by endotoxin-mediated injury.
      Treatment of these mice with Fg4497, a prolyl hydroxylase domain 2 (PHD2)
      inhibitor, activated HIF2alpha-mediated transcription in a hypoxia-independent
      manner. HIF2alpha activation increased VE-PTP expression, decreased VE-cadherin
      phosphorylation, promoted AJ integrity, and prevented the loss of endothelial
      barrier function. These findings demonstrate that HIF2alpha enhances endothelial
      barrier integrity, in part through VE-PTP expression and the resultant VE
      cadherin dephosphorylation-mediated assembly of AJs. Moreover, activation of
      HIF2alpha/VE-PTP signaling via PHD2 inhibition has the potential to prevent the
      formation of leaky vessels and edema in inflammatory diseases such as ARDS. 

PMID- 25574838
TI  - Polycystin-1 maturation requires polycystin-2 in a dose-dependent manner.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited
      nephropathy responsible for 4%-10% of end-stage renal disease cases. Mutations in
      the genes encoding polycystin-1 (PC1, PKD1) or polycystin-2 (PC2, PKD2) cause
      ADPKD, and PKD1 mutations are associated with more severe renal disease. PC1 has
      been shown to form a complex with PC2, and the severity of PKD1-mediated disease
      is associated with the level of the mature PC1 glycoform. Here, we demonstrated
      that PC1 and PC2 first interact in the ER before PC1 cleavage at the GPS/GAIN
      site and determined that PC2 acts as an essential chaperone for PC1 maturation
      and surface localization. The chaperone function of PC2 was dependent on the
      presence of the distal coiled-coil domain and was disrupted by pathogenic
      missense mutations. In Pkd2-/- mice, complete loss of PC2 prevented PC1
      maturation. In Pkd2 heterozygotes, the 50% PC2 reduction resulted in a
      nonequimolar reduction (20%-25%) of the mature PC1 glycoform. Interbreeding
      between various Pkd1 and Pkd2 models revealed that animals with reduced levels of
      functional PC1 and PC2 in the kidney exhibited severe, rapidly progressive
      disease, illustrating the importance of complexing of these proteins for
      function. Our results indicate that PC2 regulates PC1 maturation; therefore,
      mature PC1 levels are a determinant of disease severity in PKD2 as well as PKD1. 

PMID- 25574839
TI  - Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone
      remodeling.
AB  - Osteoclasts are bone-resorbing cells that are important for maintenance of bone
      remodeling and mineral homeostasis. Regulation of osteoclast differentiation and
      activity is important for the pathogenesis and treatment of diseases associated
      with bone loss. Here, we demonstrate that retinoid X receptors (RXRs) are key
      elements of the transcriptional program of differentiating osteoclasts. Loss of
      RXR function in hematopoietic cells resulted in formation of giant, nonresorbing
      osteoclasts and increased bone mass in male mice and protected female mice from
      bone loss following ovariectomy, which induces osteoporosis in WT females. The
      increase in bone mass associated with RXR deficiency was due to lack of
      expression of the RXR-dependent transcription factor v-maf musculoaponeurotic
      fibrosarcoma oncogene family, protein B (MAFB) in osteoclast progenitors.
      Evaluation of osteoclast progenitor cells revealed that RXR homodimers directly
      target and bind to the Mafb promoter, and this interaction is required for proper
      osteoclast proliferation, differentiation, and activity. Pharmacological
      activation of RXRs inhibited osteoclast differentiation due to the formation of
      RXR/liver X receptor (LXR) heterodimers, which induced expression of sterol
      regulatory element binding protein-1c (SREBP-1c), resulting in indirect MAFB
      upregulation. Our study reveals that RXR signaling mediates bone homeostasis and
      suggests that RXRs have potential as targets for the treatment of bone
      pathologies such as osteoporosis. 

PMID- 25574840
TI  - UCP2-induced fatty acid synthase promotes NLRP3 inflammasome activation during
      sepsis.
AB  - Cellular lipid metabolism has been linked to immune responses; however, the
      precise mechanisms by which de novo fatty acid synthesis can regulate
      inflammatory responses remain unclear. The NLRP3 inflammasome serves as a
      platform for caspase-1-dependent maturation and secretion of proinflammatory
      cytokines. Here, we demonstrated that the mitochondrial uncoupling protein-2
      (UCP2) regulates NLRP3-mediated caspase-1 activation through the stimulation of
      lipid synthesis in macrophages. UCP2-deficient mice displayed improved survival
      in a mouse model of polymicrobial sepsis. Moreover, UCP2 expression was increased
      in human sepsis. Consistently, UCP2-deficient mice displayed impaired lipid
      synthesis and decreased production of IL-1beta and IL-18 in response to LPS
      challenge. In macrophages, UCP2 deficiency suppressed NLRP3-mediated caspase-1
      activation and NLRP3 expression associated with inhibition of lipid synthesis. In
      UCP2-deficient macrophages, inhibition of lipid synthesis resulted from the
      downregulation of fatty acid synthase (FASN), a key regulator of fatty acid
      synthesis. FASN inhibition by shRNA and treatment with the chemical inhibitors
      C75 and cerulenin suppressed NLRP3-mediated caspase-1 activation and inhibited
      NLRP3 and pro-IL-1beta gene expression in macrophages. In conclusion, our results
      suggest that UCP2 regulates the NLRP3 inflammasome by inducing the lipid
      synthesis pathway in macrophages. These results identify UCP2 as a potential
      therapeutic target in inflammatory diseases such as sepsis. 

PMID- 25574844
TI  - Magnolol Inhibits RANKL-induced osteoclast differentiation of raw 264.7
      macrophages through heme oxygenase-1-dependent inhibition of NFATc1 expression.
AB  - Magnolol (1) isolated from Magnolia officinalis exhibits many beneficial effects
      such as anti-inflammatory and antioxidant activity. The aim of this study was to
      evaluate the effects of magnolol (1) on RANKL-induced osteoclast differentiation
      and investigate the underlying molecular mechanisms. Treatment with magnolol (1)
      significantly inhibited osteoclast differentiation of RAW 264.7 macrophages and
      bone-resorbing activity of osteoclasts in the RANKL-induced system. Moreover,
      RANKL-activated JNK/ERK/AP-1 and NF-kappaB signaling, ROS formation, and NFATc1
      activation were attenuated by magnolol (1). A novel finding of this study is that
      magnolol (1) can increase heme oxygenase-1 (HO-1) expression and Nrf2 activation
      in RANKL-stimulated cells. Blocking HO-1 activity with tin protoporphyrin IX
      markedly reversed magnolol (1)-mediated inhibition of osteoclast differentiation,
      NFATc1 nuclear translocation, and MMP-9 activity, suggesting that HO-1
      contributes to the attenuation of NFATc1-mediated osteoclastogenesis by magnolol
      (1). Therefore, the inhibitory effect of magnolol (1) on osteoclast
      differentiation is due to inhibition of MAPK/c-fos/AP-1 and NF-kappaB signaling
      as well as ROS production and up-regulation of HO-1 expression, which ultimately
      suppresses NFATc1 induction. These findings indicate that magnolol (1) may have
      potential to treat bone diseases associated with excessive osteoclastogenesis. 

PMID- 25574843
TI  - Dysregulation of microRNA-219 promotes neurodegeneration through post
      transcriptional regulation of tau.
AB  - Tau is a highly abundant and multifunctional brain protein that accumulates in
      neurofibrillary tangles (NFTs), most commonly in Alzheimer's disease (AD) and
      primary age-related tauopathy. Recently, microRNAs (miRNAs) have been linked to
      neurodegeneration; however, it is not clear whether miRNA dysregulation
      contributes to tau neurotoxicity. Here, we determined that the highly conserved
      brain miRNA miR-219 is downregulated in brain tissue taken at autopsy from
      patients with AD and from those with severe primary age-related tauopathy. In a
      Drosophila model that produces human tau, reduction of miR-219 exacerbated tau
      toxicity, while overexpression of miR-219 partially abrogated toxic effects.
      Moreover, we observed a bidirectional modulation of tau levels in the Drosophila
      model that was dependent on miR-219 expression or neutralization, demonstrating
      that miR-219 regulates tau in vivo. In mammalian cellular models, we found that
      miR-219 binds directly to the 3'-UTR of the tau mRNA and represses tau synthesis
      at the post-transcriptional level. Together, our data indicate that silencing of
      tau by miR-219 is an ancient regulatory mechanism that may become perturbed
      during neurofibrillary degeneration and suggest that this regulatory pathway may
      be useful for developing therapeutics for tauopathies. 

PMID- 25574845
TI  - Organophosphorus insecticides in honey, pollen and bees (Apis mellifera L.) and
      their potential hazard to bee colonies in Egypt.
AB  - There is no clear single factor to date that explains colony loss in bees, but
      one factor proposed is the wide-spread application of agrochemicals.
      Concentrations of 14 organophosphorous insecticides (OPs) in honey bees (Apis
      mellifera) and hive matrices (honey and pollen) were measured to assess their
      hazard to honey bees. Samples were collected during spring and summer of 2013,
      from 5 provinces in the middle delta of Egypt. LC/MS-MS was used to identify and
      quantify individual OPs by use of a modified Quick Easy Cheap Effective Rugged
      Safe (QuEChERS) method. Pesticides were detected more frequently in samples
      collected during summer. Pollen contained the greatest concentrations of OPs.
      Profenofos, chlorpyrifos, malation and diazinon were the most frequently detected
      OPs. In contrast, ethoprop, phorate, coumaphos and chlorpyrifos-oxon were not
      detected. A toxic units approach, with lethality as the endpoint was used in an
      additive model to assess the cumulative potential for adverse effects posed by
      OPs. Hazard quotients (HQs) in honey and pollen ranged from 0.01-0.05 during
      spring and from 0.02-0.08 during summer, respectively. HQs based on lethality due
      to direct exposure of adult worker bees to OPs during spring and summer ranged
      from 0.04 to 0.1 for best and worst case respectively. It is concluded that
      direct exposure and/or dietary exposure to OPs in honey and pollen pose little
      threat due to lethality of bees in Egypt. 

PMID- 25574846
TI  - Bacillus species isolated from tungrymbai and bekang, naturally fermented soybean
      foods of India.
AB  - Tungrymbai and bekang are naturally fermented soybean foods commonly consumed in
      Meghalaya and Mizoram states of India. A total of 39 samples of tungrymbai and 43
      samples of bekang were collected from different villages and markets of Meghalaya
      and Mizoram, respectively and were analysed for microbial load. In both
      tungrymbai and bekang, the average population of Bacillus spp. was 8.2+/-0.1 log
      cfu/g. A total of 428 isolates of Bacillus were isolated from tungrymbai (211)
      and bekang (217) for detailed identification. On the basis of a combination of
      phenotypic and molecular characterisation using ARDRA, ITS-PCR and RAPD-PCR
      techniques, species of Bacillus isolated from tungrymbai were identified as
      Bacillus licheniformis (25.5%), Bacillus pumilus (19.5%) and Bacillus subtilis
      (55%), and species of Bacillus from bekang were Bacillus brevis (2%), Bacillus
      circulans (7.5%), Bacillus coagulans (6.5%), B. licheniformis (16.5%), B. pumilus
      (9.1%), Bacillus sphaericus (4.6%), B. subtilis (51.8%), and Lysinibacillus
      fusiformis (2%). The most dominant bacterium in both products was B. subtilis.

PMID- 25574841
TI  - Global transcriptional disturbances underlie Cornelia de Lange syndrome and
      related phenotypes.
AB  - Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder that
      presents with extensive phenotypic variability, including facial dysmorphism,
      developmental delay/intellectual disability (DD/ID), abnormal extremities, and
      hirsutism. About 65% of patients harbor mutations in genes that encode subunits
      or regulators of the cohesin complex, including NIPBL, SMC1A, SMC3, RAD21, and
      HDAC8. Wiedemann-Steiner syndrome (WDSTS), which shares CdLS phenotypic features,
      is caused by mutations in lysine-specific methyltransferase 2A (KMT2A). Here, we
      performed whole-exome sequencing (WES) of 2 male siblings clinically diagnosed
      with WDSTS; this revealed a hemizygous, missense mutation in SMC1A that was
      predicted to be deleterious. Extensive clinical evaluation and WES of 32 Turkish
      patients clinically diagnosed with CdLS revealed the presence of a de novo
      heterozygous nonsense KMT2A mutation in 1 patient without characteristic WDSTS
      features. We also identified de novo heterozygous mutations in SMC3 or SMC1A that
      affected RNA splicing in 2 independent patients with combined CdLS and WDSTS
      features. Furthermore, in families from 2 separate world populations segregating
      an autosomal-recessive disorder with CdLS-like features, we identified homozygous
      mutations in TAF6, which encodes a core transcriptional regulatory pathway
      component. Together, our data, along with recent transcriptome studies, suggest
      that CdLS and related phenotypes may be "transcriptomopathies" rather than
      cohesinopathies. 

PMID- 25574842
TI  - NOTCH pathway inactivation promotes bladder cancer progression.
AB  - NOTCH signaling suppresses tumor growth and proliferation in several types of
      stratified epithelia. Here, we show that missense mutations in NOTCH1 and NOTCH2
      found in human bladder cancers result in loss of function. In murine models,
      genetic ablation of the NOTCH pathway accelerated bladder tumorigenesis and
      promoted the formation of squamous cell carcinomas, with areas of mesenchymal
      features. Using bladder cancer cells, we determined that the NOTCH pathway
      stabilizes the epithelial phenotype through its effector HES1 and, consequently,
      loss of NOTCH activity favors the process of epithelial-mesenchymal transition.
      Evaluation of human bladder cancer samples revealed that tumors with low levels
      of HES1 present mesenchymal features and are more aggressive. Together, our
      results indicate that NOTCH serves as a tumor suppressor in the bladder and that
      loss of this pathway promotes mesenchymal and invasive features. 

PMID- 25574847
TI  - Anaerobic sporeformers and their significance with respect to milk and dairy
      products.
AB  - Sporeforming bacteria are a significant concern for the international dairy
      industry. Spores present in milk survive heat treatments and can persist during
      downstream processing. If they are present in sufficient numbers in dairy
      products they can cause spoilage or lead to illness as a result of toxin
      production. While many reviews have highlighted the threat posed by spores of
      aerobic bacteria to the dairy industry, few have focused on problems caused by
      the array of different species of anaerobic sporeformers (Clostridium and related
      genera) that can be found in milk. This is despite of the fact that members of
      these bacteria are found throughout the dairy farm environment, and can be
      toxigenic, neurotoxigenic or spoilage bacteria. This makes the possible presence
      of Clostridium and related spores in bulk tank milk (BTM) important from both a
      financial and a public health perspective. In this review dairy associated
      anaerobic sporeformers are assessed from a number of perspectives. This includes
      the taxonomy of this group of bacteria, the important subgroup of this genus the
      "sulphite reducing clostridia" (SRC), how these bacteria are detected in milk
      products, the epidemiological data regarding pathogenic species and strains
      within the SRC group as well as the influence of farming practices on the
      presence of SRC in BTM.

PMID- 25574850
TI  - Correction: High Density Lipoprotein Stimulated Migration of Macrophages Depends
      on the Scavenger Receptor Class B, Type I, PDZK1 and Akt1 and Is Blocked by
      Sphingosine 1 Phosphate Receptor Antagonists.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0106487.]. 

PMID- 25574848
TI  - Annexin II-dependent actin remodelling evoked by hydrogen peroxide requires the
      metalloproteinase/sphingolipid pathway.
AB  - Actin remodeling is a dynamic process associated with cell shape modification
      occurring during cell cycle and proliferation. Oxidative stress plays a role in
      actin reorganization via various systems including p38MAPK. Beside, the mitogenic
      response evoked by hydrogen peroxide (H2O2) in fibroblasts and smooth muscle
      cells (SMC) involves the metalloproteinase (MMPs)/sphingomyelinase 2 (nSMase2)
      signaling pathway. The aim of this work was to investigate whether this system
      plays a role in actin remodeling induced by H2O2. Low H2O2 dose (5uM) rapidly
      triggered a signaling cascade leading to nSMase2 activation, src and annexin 2
      (AnxA2) phosphorylation, and actin remodeling, in fibroblasts and SMC. These
      events were blocked by pharmacological inhibitors of MMPs (Ro28-2653) and p38MAPK
      (SB203580), and were lacking in MMP2(-/-) and in nSMase2-mutant (fro)
      fibroblasts. Likewise, H2O2 was unable to induce actin remodeling in fro and
      MMP2(-/-) fibroblasts or in cells pretreated with p38MAPK, or MMP inhibitors.
      Finally we show that nSMase2 activation by H2O2, depends on MMP2 and p38MAPK, and
      is required for the src-dependent phosphorylation of AnxA2, and actin remodeling.
      Taken together, these findings indicate for the first time that AnxA2
      phosphorylation and actin remodeling evoked by oxidative stress depend on the
      sphingolipid pathway, via MMP2 and p38MAPK. 

PMID- 25574849
TI  - Phenotype classification of zebrafish embryos by supervised learning.
AB  - Zebrafish is increasingly used to assess biological properties of chemical
      substances and thus is becoming a specific tool for toxicological and
      pharmacological studies. The effects of chemical substances on embryo survival
      and development are generally evaluated manually through microscopic observation
      by an expert and documented by several typical photographs. Here, we present a
      methodology to automatically classify brightfield images of wildtype zebrafish
      embryos according to their defects by using an image analysis approach based on
      supervised machine learning. We show that, compared to manual classification,
      automatic classification results in 90 to 100% agreement with consensus voting of
      biological experts in nine out of eleven considered defects in 3 days old
      zebrafish larvae. Automation of the analysis and classification of zebrafish
      embryo pictures reduces the workload and time required for the biological expert
      and increases the reproducibility and objectivity of this classification. 

PMID- 25574851
TI  - Utilization of recycled asphalt concrete with warm mix asphalt and cost-benefit
      analysis.
AB  - The asphalt paving industries are faced with two major problems. These two
      important challenges are generated with an increase in demand for environmentally
      friendly paving mixtures and the problem of rapidly rising raw materials.
      Recycling of reclaimed asphalt pavement (RAP) is a critical necessity to save
      precious aggregates and reduce the use of costly bitumen. Warm Mix Asphalt (WMA)
      technology provides not only the option of recycling asphalt pavement at a lower
      temperature than the temperature maintained in hot mixtures but also encourages
      the utilization of RAP and therefore saves energy and money. This paper describes
      the feasibility of utilizing three different WMA additives (organic, chemical and
      water containing) at recommended contents with different percentages of RAP. The
      mechanical properties and cost-benefit analysis of WMA containing RAP have been
      performed and compared with WMA without RAP. The results indicated that, 30%, 10%
      and 20% can be accepted as an optimum RAP addition related to organic, chemical
      and water containing additives respectively and organic additive with 30% RAP
      content has an appreciable increase in tensile strength over the control mix. It
      was also concluded that the RAP with WMA technology is the ability to reduce
      final cost compared to HMA and WMA mixtures. 

PMID- 25574852
TI  - Bonding in nitroxide spin labels from 14N electric-quadrupole interactions.
AB  - Nitrogen nuclear electric quadrupole couplings from FT-EPR of nitroxide spin
      labels can be used to deduce the covalent transfer pic in the N-O pi-bond, and
      ionicities isigma(NO) and isigma(NC) of the N-O and N-C sigma-bonds, if they are
      combined with the unpaired spin density on the nitrogen rhopi(N) obtained from
      the dipolar hyperfine couplings. Application to EPR data from an analogue of the
      MTSSL nitroxide that is used in site-directed spin-labeling demonstrates how
      environmental polarity and hydrogen bonding are reflected in the bonding
      parameters of the C-NO-C spin label moiety. Several recent publications
      erroneously claim to have deduced three independent bonding parameters from
      nitrogen quadrupole couplings alone.

PMID- 25574855
TI  - Thiolated hemicellulose as a versatile platform for one-pot click-type hydrogel
      synthesis.
AB  - A one-pot synthetic methodology for the thiolation of O-acetyl-galactoglucomannan
      (AcGGM) was developed to merge hemicellulose chemistry with "click" chemistry.
      This was realized by the AcGGM-mediated nucleophilic ring-opening of gamma
      thiobutyrolactone via the activation of the polysaccharide pendant hydroxyl
      groups. The incorporation of thiol functionalities onto the hemicellulose
      backbone was visualized by (1)H and (13)C NMR spectroscopy and was assessed by an
      Ellman's reagent assay of the thiol groups. The versatility of the thiolated
      AcGGM was elaborated and demonstrated by conducting several postmodification
      reactions together with hydrogel formation utilizing thiol-ene and thiol-Michael
      addition "click" reactions. The one-pot synthesis of thiolated AcGGM is a
      straightforward approach that can expand the applications of hemicelluloses
      derived from biomass by employing "click" chemistry. 

PMID- 25574854
TI  - Toward molecular catalysts by computer.
AB  - CONSPECTUS: Rational design of molecular catalysts requires a systematic approach
      to designing ligands with specific functionality and precisely tailored
      electronic and steric properties. It then becomes possible to devise computer
      protocols to design catalysts by computer. In this Account, we first review how
      thermodynamic properties such as redox potentials (E degrees ), acidity constants
      (pKa), and hydride donor abilities (DeltaGH(-)) form the basis for a framework
      for the systematic design of molecular catalysts for reactions that are critical
      for a secure energy future. We illustrate this for hydrogen evolution and
      oxidation, oxygen reduction, and CO conversion, and we give references to other
      instances where it has been successfully applied. The framework is amenable to
      quantum-chemical calculations and conducive to predictions by computer. We review
      how density functional theory allows the determination and prediction of these
      thermodynamic properties within an accuracy relevant to experimentalists (~0.06
      eV for redox potentials, ~1 pKa unit for pKa values, and 1-2 kcal/mol for
      hydricities). Computation yielded correlations among thermodynamic properties as
      they reflect the electron population in the d shell of the metal center, thus
      substantiating empirical correlations used by experimentalists. These
      correlations point to the key role of redox potentials and other properties (pKa
      of the parent aminium for the proton-relay-based catalysts designed in our
      laboratory) that are easily accessible experimentally or computationally in
      reducing the parameter space for design. These properties suffice to fully
      determine free energies maps and profiles associated with catalytic cycles, i.e.,
      the relative energies of intermediates. Their prediction puts us in a position to
      distinguish a priori between desirable and undesirable pathways and mechanisms.
      Efficient catalysts have flat free energy profiles that avoid high activation
      barriers due to low- and high-energy intermediates. The criterion of a flat
      energy profile can be mathematically resolved in a functional in the reduced
      parameter space that can be efficaciously calculated by means of the correlation
      expressions. Optimization of the functional permits the prediction by computer of
      design points for optimum catalysts. Specifically, the optimization yields the
      values of the thermodynamic properties for efficient (high rate and low
      overpotential) catalysts. We are on the verge of design of molecular
      electrocatalysts by computer. Future efforts must focus on identifying actual
      ligands that possess these properties. We believe that this can also be achieved
      through computation, using Taft-like relationships linking molecular composition
      and structure with electron-donating ability and steric effects. We note also
      that the approach adopted here of using free energy maps to decipher catalytic
      pathways and mechanisms does not account for kinetic barriers associated with
      elementary steps along the catalytic pathway, which may make thermodynamically
      accessible intermediates kinetically inaccessible. Such an extension of the
      approach will require further computations that, however, can take advantage of
      Polanyi-like linear free energy relationships linking activation barriers and
      reaction free energies.

PMID- 25574853
TI  - Small molecule disruption of quorum sensing cross-regulation in pseudomonas
      aeruginosa causes major and unexpected alterations to virulence phenotypes.
AB  - The opportunistic pathogen Pseudomonas aeruginosa uses three interwoven quorum
      sensing (QS) circuits-Las, Rhl, and Pqs-to regulate the global expression of
      myriad virulence-associated genes. Interception of these signaling networks with
      small molecules represents an emerging strategy for the development of anti
      infective agents against this bacterium. In the current study, we applied a
      chemical approach to investigate how the Las-Rhl-Pqs QS hierarchy coordinates key
      virulence phenotypes in wild-type P. aeruginosa. We screened a focused library of
      synthetic, non-native N-acyl l-homoserine lactones and identified compounds that
      can drastically alter production of two important virulence factors: pyocyanin
      and rhamnolipid. We demonstrate that these molecules act by targeting RhlR in P.
      aeruginosa, a QS receptor that has seen far less scrutiny to date relative to
      other circuitry. Unexpectedly, modulation of RhlR activity by a single compound
      induces inverse regulation of pyocyanin and rhamnolipid, a result that was not
      predicted using genetic approaches to interrogate QS in P. aeruginosa. Further,
      we show that certain RhlR agonists strongly repress Pqs signaling, revealing
      disruption of Rhl-Pqs cross-regulation as a novel mechanism for QS inhibition.
      These compounds significantly expand the known repertoire of chemical probes
      available to study RhlR in P. aeruginosa. Moreover, our results suggest that
      designing chemical agents to disrupt Rhl-Pqs crosstalk could be an effective
      antivirulence strategy to fight this common pathogen. 

PMID- 25574856
TI  - Generation of Rashba spin-orbit coupling in CdSe nanowire by ionic liquid gate.
AB  - Spintronic devices rely on the spin degree of freedom (DOF), and spin orbit
      coupling (SOC) is the key to manipulate spin DOF. Quasi-one-dimensional
      structures, possessing marked anisotropy gives more choice for the manipulation
      of the spin DOF since the concrete SOC form varies along with crystallographic
      directions. The anisotropy of the Dresselhaus SOC in cadmium selenide (CdSe)
      nanobelt and nanowire was studied by circular photogalvanic effect. It was
      demonstrated that the Dresselhaus SOC parameter is zero along the [0001]
      crystallographic direction, which suppresses the spin relaxation and increases
      the spin diffusion length, and thus is beneficial to the spin manipulation. To
      achieve a device structure with Rashba SOC presence and Dresselhaus SOC absence
      for manipulating the spin DOF, an ionic liquid gate was produced on a nanowire
      grown along the [0001] crystallographic direction, and the Rashba SOC was induced
      by gating, as expected. 

PMID- 25574857
TI  - Lipoprotein concentration, particle number, size and cholesterol efflux capacity
      are associated with mitochondrial oxidative stress and function in an HIV
      positive cohort.
AB  - BACKGROUND: Association of lipoprotein particle size/number and HDL function with
      mitochondrial oxidative stress and function may underlie the excess
      cardiovascular (CVD) risk in HIV. METHODS AND RESULTS: Among HIV infected
      individuals on stable highly active antiretroviral therapy, we related standard
      and novel lipid measures [plasma total cholesterol, triglycerides, HDL-C, LDL-C,
      lipoprotein particle (-P) subclass size and number and HDL function (via
      cholesterol-efflux capacity)] with oxidative stress [peripheral blood mononuclear
      cell's mitochondrial-specific 8-oxo-deoxyguanine (8-oxo-dG)] and function markers
      [oxidative phosphorylation (OXPHOS) NADH dehydrogenase (Complex I) and cytochrome
      c oxidase (Complex IV) enzyme activities]. Multivariable-adjusted logistic and
      linear regression analyses were employed adjusting for age, gender, CD4 nadir,
      viral load, smoking, diabetes, HOMA-IR, hypertension and lipid medications. Among
      150 HIV-infected persons (mean age 52 years, 12% women, median CD4 count 524
      cell/mm3), low HDL-C and high total cholesterol/HDL-C ratio were related to PBMC
      8-oxo-deoxyguanine (p = 0.01 and 0.02 respectively). Large HDL-P and HDL-P size
      were inversely related to PBMC 8-oxo-deoxyguanine (p = 0.04). Small LDL-P (p =
      0.01) and total LDL-P (p = 0.01) were related to decreased OXPHOS Complex I
      activity. LDL-P was related to decreased OXPHOS Complex IV activity (p = 0.02).
      Cholesterol efflux capacity was associated with increased OXPHOS Complex IV
      activity. CONCLUSIONS: HDL concentration and particle size and number are related
      to decreased PBMC mitochondrial oxidative stress whereas HDL function is
      positively related to mitochondrial oxidative function. The association we find
      between atherogenic lipoprotein profile and increased oxidative stress and
      function suggests these pathways may be important in the pathogenesis of
      cardiometabolic disease in HIV disease.

PMID- 25574858
TI  - Plasma soluble urokinase-type plasminogen activator receptor level is
      independently associated with coronary microvascular function in patients with
      non-obstructive coronary artery disease.
AB  - BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a
      novel biomarker released from leukocytes and endothelial cells that has been
      associated with atherosclerotic cardiovascular disease. We hypothesized that
      plasma suPAR level is an independent predictor of coronary microvascular
      function. METHODS: Coronary blood flow velocity and plasma suPAR levels were
      evaluated in patients with non-obstructive coronary artery disease. Coronary flow
      reserve (CFR) was calculated as the ratio of hyperemic to basal average peak
      blood flow velocity and coronary microvascular dysfunction was defined as CFR <=
      2.0 in the setting of a fractional flow reserve value of >=0.75. Plasma suPAR
      levels were measured using ELISA technique. The association between suPAR and CFR
      was investigated using univariate and multivariate regression analyses. RESULTS:
      In 66 patients, 47% were men, 26% had diabetes, 68% had hypertension and 76% had
      dyslipidemia. Mean age was 55 +/- 12 years and median suPAR level 2.82 (2.08
      3.40) ng/mL. Plasma suPAR levels correlated with age (r = 0.31, p = 0.01), body
      mass index (r = 0.25, p = 0.04) and high-sensitivity C-reactive protein (hs-CRP)
      (r = 0.33, p = 0.009). While median suPAR level was not significantly different
      in patients with different cardiovascular risk factors, patients on statin
      therapy had significantly higher suPAR level (p = 0.03). SuPAR correlated
      negatively with CFR and, after multivariate adjustment for established
      cardiovascular risk factors, medications profiles and hs-CRP, suPAR remained an
      independent predictor of CFR (B = -0.30, p = 0.04), indicating an independent
      association between suPAR level and coronary microvascular function. CONCLUSIONS:
      In this cross-sectional study, plasma suPAR level was an independent predictor of
      coronary microvascular function. Larger prospective clinical trials are warranted
      to investigate the prognostic value of this novel biomarker and the role of
      immune dysregulation in coronary microvascular disease.

PMID- 25574860
TI  - Fluorescence sensing of chromium (VI) and ascorbic acid using graphitic carbon
      nitride nanosheets as a fluorescent "switch".
AB  - Using graphitic carbon nitride (g-C3N4) nanosheets, an effective and facile
      fluorescence sensing approach for the label-free and selective determination of
      chromium (VI) (Cr(VI)) was developed. The fluorescence of the solution of g-C3N4
      nanosheets was quenched effectively by Cr(VI) via the inner filter effect. Under
      optimal conditions, a wide detection linear range for Cr(VI) was found to be from
      0.6 MUM to 300 MUM with a limit of detection (LOD) of 0.15 MUM. In addition, the
      fluorescence of the solution of g-C3N4 nanosheets-Cr(VI) could be sensitively
      turned on in the presence of a reductant such as ascorbic acid (AA) via an "on
      off-on" fluorescence response through the oxidation-reduction between Cr(VI) and
      AA. And a wide detection linear range for AA was found to be from 0.5 MUM to 200
      MUM with an LOD of 0.13 MUM. Furthermore, the proposed method has the potential
      application for detection of Cr(VI) in lake waters and AA in biological fluids.

PMID- 25574859
TI  - Leptin and incident cardiovascular disease: the Multi-ethnic Study of
      Atherosclerosis (MESA).
AB  - OBJECTIVE: Higher serum leptin levels have been associated with a modestly higher
      incidence of cardiovascular disease in studies involving mostly Caucasian men. We
      aimed to assess the hypothesis that higher baseline levels of serum leptin are
      associated with higher risk of future cardiovascular disease in a diverse cohort.
      METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a modern, community
      based, ethnically-diverse, and sex-balanced prospective cohort study of US adults
      free from cardiovascular disease. Serum leptin was measured in an ancillary study
      in 2002-2005. This analysis included 1905 MESA participants with baseline leptin
      and incident cardiovascular event data. Leptin levels were modeled as a log
      transformed continuous variable and multivariable-adjusted Cox regression was
      performed for the primary outcome of hard cardiovascular disease, including
      coronary heart disease and stroke. RESULTS: The median follow-up was 7.6 years
      (25th-75th 7.1-8.3) with 7051 and 6738 person-years of follow-up in women and
      men. A hard cardiovascular disease event occurred in 47 women and 63 men. The age
      and ethnicity-adjusted hazard ratio estimates for a 1 standard deviation
      increase in ln(leptin) were 1.16 in women (95% CI 0.78-1.73, p = 0.46) and 0.91
      (95% CI 0.69-1.20, p = 0.51) in men. Pooling sexes, and adjusting for sex in
      addition to age and ethnicity, estimates were 0.98 (95% CI 0.78-1.23, p = 0.89).
      With additional adjustment for cardiovascular risk factors, the results remained
      nonsignificant: 0.87 (95% CI 0.68-1.11, p = 0.26). CONCLUSION: In conclusion, in
      a modern, US prospective cohort study of multi-ethnic women and men of multi
      ethnic backgrounds, leptin levels are not associated with incident cardiovascular
      events.

PMID- 25574861
TI  - A fluorescent nanosensor based on graphene quantum dots-aptamer probe and
      graphene oxide platform for detection of lead (II) ion.
AB  - The sensitive detection of heavy metal ions in the organism and aquatic ecosystem
      using nanosensors based on environment friendly and biocompatible materials still
      remains a challenge. A fluorescent turn-on nanosensor for lead (II) detection
      based on biocompatible graphene quantum dots and graphene oxide by employment of
      Pb(2+)-induced G-quadruplex formation was reported. Graphene quantum dots with
      high quantum yield, good biocompatibility were prepared and served as the
      fluorophore of Pb(2+) probe. Fluorescence turn-off of graphene quantum dots is
      easily achieved through efficient photoinduced electron transfer between graphene
      quantum dots and graphene oxide, and subsequent fluorescence turn-on process is
      due to the formation of G-quadraplex aptamer-Pb(2+) complex triggered by the
      addition of Pb(2+). This nanosensor can distinguish Pb(2+) ion from other ions
      with high sensitivity and good reproducibility. The detection method based on
      this nanosensor possesses a fast response time of one minute, a broad linear span
      of up to 400.0 nM and ultralow detection limit of 0.6 nM.

PMID- 25574863
TI  - "Soft" confinement of graphene in hydrogel matrixes.
AB  - Graphene plays as protagonist among the newly discovered carbon nanomaterials on
      the laboratory bench. Confinement of graphene, combined with enhanced exchange
      properties within aqueous environment, is key for the development of biosensors,
      biomedicine devices, and water remediation applications. Such confinement is
      possible using hydrogels as soft matrixes. Many entrapment methods focused on the
      modification of the graphene structure. In this paper, however, we address a
      confinement method that leaves unchanged the graphene structure, although
      intimately participating in the buildup of a network of polyvinyl alcohol (PVA)
      chains. PVA is a polymer known as biomaterial for its hydrophilicity,
      biocompatibility, and chemical versatility. A robust hybrid PVA-graphene
      construct was obtained starting from a surfactant-assisted sonication of an
      aqueous dispersion of graphite. Stable graphene sheets suspension was
      photopolymerized in a methacryloyl-grafted PVA, using the vinyl moiety present on
      the surfactant scaffold. This method can allow the incorporation in the polymer
      network of oligomers of N-(isopropylacrylammide), p(NiPAAm). These chains display
      in aqueous solution a low critical solution temperature, LCST, around 33  degrees
      C and trigger a volume phase transition when incorporated in a hydrophilic
      network around the physiological temperature. Raman analysis was used to
      characterize the state of hydrogel embedded graphene single sheets. Evidence for
      an intimate interaction of graphene sheets and polymer matrix was collected.
      Release of the anticancer drug doxorubicin showed the active role of the
      graphene/PVA/p(NiPAAm) construct in the drug delivery.

PMID- 25574862
TI  - Non-organic language deficits following awake brain surgery: a case report.

PMID- 25574865
TI  - A review of the use of simulation in dental education.
AB  - In line with the advances in technology and communication, medical simulations
      are being developed to support the acquisition of requisite psychomotor skills
      before real-life clinical applications. This review article aimed to give a
      general overview of simulation in a cognate field, clinical dental education.
      Simulations in dentistry are not a new phenomenon; however, recent developments
      in virtual-reality technology using computer-generated medical simulations of 3
      dimensional images or environments are providing more optimal practice conditions
      to smooth the transition from the traditional model-based simulation laboratory
      to the clinic. Evidence as to the positive aspects of virtual reality include
      increased effectiveness in comparison with traditional simulation teaching
      techniques, more efficient learning, objective and reproducible feedback,
      unlimited training hours, and enhanced cost-effectiveness for teaching
      establishments. Negative aspects have been indicated as initial setup costs,
      faculty training, and the lack of a variety of content and current educational
      simulation programs.

PMID- 25574864
TI  - Relationship between body dissatisfaction and disordered eating: mediating role
      of self-esteem and depression.
AB  - The purpose of this study was to investigate the hypothesis that the effect of
      body dissatisfaction on disordered eating behavior is mediated through self
      esteem and depression. If the effect of body dissatisfaction on disordered eating
      can be explained by self-esteem and depression, treatment may benefit from
      focusing more on self-esteem and depression than body dissatisfaction. We also
      hypothesized body image importance to be associated with lower self-esteem,
      stronger symptoms of depression, and more disordered eating. The results showed
      that the effect of body dissatisfaction on disorder eating was completely
      mediated, whereas the effect of body image importance was partly mediated. Both
      self-esteem and depression were significant mediators. Body image importance and
      self-esteem had a direct effect on restrained eating and compensatory behavior.
      Depression had a direct effect on binge eating. This effect was significantly
      stronger among women. Depression also had a direct effect on restrained eating.
      This effect was positive among women, but negative among men. The results support
      emotion regulation and cognitive behavioral theories of eating disorders,
      indicating that self-esteem and depression are the most proximal factors, whereas
      the effect of body dissatisfaction is indirect. The results point out the
      importance of distinguishing between different symptoms of bulimia. Depression
      may cause binge eating, but compensatory behavior depends on self-esteem and body
      image importance. The results suggest that women may turn to both binge eating
      and restrained eating to escape awareness of negative emotions, whereas men focus
      on eating to a lesser extent than women. Existing treatment focuses on eating
      behavior first and mechanisms such as self-esteem and depression second. The
      results from this study suggest that an earlier focus on self-esteem and
      depression may be warranted in the treatment of disordered eating. 

PMID- 25574866
TI  - High-fidelity simulation of transcutaneous cardiac pacing: characteristics and
      limitations of available high-fidelity simulators, and description of an
      alternative two-mannequin model.
AB  - INTRODUCTION: Transcutaneous cardiac pacing (TCP) is a potentially lifesaving
      technique that is part of the recommended treatment for symptomatic bradycardia.
      Transcutaneous cardiac pacing however is used uncommonly, and its successful
      application is not straightforward. Simulation could, therefore, play an
      important role in the teaching and assessment of TCP competence. However, even
      the highest-fidelity mannequins available on the market have important
      shortcomings, which limit the potential of simulation. METHODS: Six criteria
      defining clinical competency in TCP were established and used as a starting point
      in the creation of an improved TCP simulator. The goal was a model that could be
      used to assess experienced clinicians, an objective that justifies the additional
      effort required by the increased fidelity. RESULTS: The proposed 2-mannequin
      model (TMM) combines a highly modified Human Patient Simulator with a SimMan 3G,
      the latter being used solely to provide the electrocardiography (ECG) tracing.
      The TMM improves the potential of simulation to assess experienced clinicians (1)
      by reproducing key features of TCP, like using the same multifunctional pacing
      electrodes used clinically, allowing dual ECG monitoring, and responding with
      upper body twitching when stimulated, but equally importantly (2) by reproducing
      key pitfalls of the technique, like allowing pacing electrode misplacement and
      reproducing false signs of ventricular capture, commonly, but erroneously, used
      clinically to establish that effective pacing has been achieved (like body
      twitching, electrical artifact on the ECG, and electrical capture without
      ventricular capture). CONCLUSIONS: The proposed TMM uses a novel combination of 2
      high-fidelity mannequins to improve TCP simulation until upgraded mannequins
      become commercially available.

PMID- 25574867
TI  - A robust and inexpensive phantom for fluoroscopically guided lumbar puncture
      training.
AB  - INTRODUCTION: This report describes the creation process for an inexpensive,
      durable, lumbar spine phantom for use in fluoroscopically guided lumbar puncture
      (LP) training. METHODS: The LP phantom prototype was made from a polyvinyl
      chloride lumbar spine model embedded in a translucent rectangular block of
      commercially available thermoplastic polymer gel. Radiology residents with
      limited previous experience performing LP used the phantom for 20 simulated
      procedures to gain confidence before starting patient procedures. The residents
      completed surveys detailing their experiences with the phantom. RESULTS:
      Quantitative evaluation of the phantom using fluoroscopy and computed tomography
      suggested good physical agreement with human anatomy. Six board-certified
      radiologists viewed the phantom under live fluoroscopy and indicated that the
      phantom represented human anatomy with sufficient accuracy. Furthermore, surveys
      from resident trainees indicated that the thermoplastic tissue substitute
      simulated the texture and resistance of human soft tissue reasonably well for the
      purposes of clinical training. The total material cost of the LP phantom
      prototype was approximately US $148.00. CONCLUSIONS: This novel spine phantom can
      be produced with relatively low cost when compared with similar commercially
      available products. The phantom offers reasonable visual and tactile agreement to
      human anatomy and may be useful for improving the confidence of physician
      trainees. The LP phantom is durable and can easily be repaired by reheating the
      polymer tissue substitute.

PMID- 25574868
TI  - Development of a novel task trainer for second trimester ultrasound-guided
      uterine evacuation.
AB  - INTRODUCTION: Second trimester surgical termination of pregnancy by dilation and
      evacuation (D&E) is a procedure that the Obstetrics and Gynecology (OB/GYN)
      Residency Review Committee requires training programs to offer to their residents
      and that many residents desire to learn. However, because of limited numbers of
      credentialed providers, clinical training opportunities may be limited or not
      available at their training institutions. Simulated procedures may allow for
      residents and other learners to be more prepared and capable at the time of their
      first clinical procedures or advanced skill acquisition. METHODS: We describe the
      construction of a low-cost task trainer for simulation of ultrasound-guided
      second trimester uterine evacuation procedures using a preserved pig heart and
      fetal pig. Residents of OB/GYN used the task trainer and completed a survey to
      determine its effectiveness as a teaching tool. RESULTS: With the use of a 5
      point Likert scale survey (1 inferior, 5 superior), 13 OB/GYN trainees felt that
      the task trainer reliably reproduced fetal extraction (4.08), would improve their
      clinical skills (4.46), and would allow them to obtain the skills required to
      perform the task in real life (4.38). The similarity of ultrasound images to real
      life images had a mean score of 3.69. Additional comments about the usefulness of
      this task trainer in learning the skills necessary for D&E procedures from the
      participants were overall positive. CONCLUSIONS: The task trainer for ultrasound
      guided second trimester uterine evacuation showed excellent face validity. This
      low-cost task trainer provides residents and other trainees with a tool to
      practice ultrasound-guided fetal extraction skills and improve proficiency with
      D&E outside the operating room. In addition, it increases their confidence in
      being able to perform the procedure on patients.

PMID- 25574870
TI  - Using the socio-ecological framework to determine breastfeeding obstacles in a
      low-income population in Tijuana, Mexico: healthcare services.
AB  - BACKGROUND: In Mexico, breastfeeding rates are one of the lowest of Latin
      America, with 14.4% of infants under 6 months being exclusively breastfed.
      Previous studies indicate that lack of support from healthcare services is a
      serious obstacle to breastfeeding mothers in Mexico. Our objective was to
      identify the main obstacles to breastfeeding presented by the healthcare services
      in a low-income population in Tijuana, Mexico. MATERIALS AND METHODS: We used a
      socio-ecological framework to determine factors affecting breastfeeding
      practices. In four low-income communities in Tijuana we conducted focus groups
      and interviews with mothers, fathers, grandparents, and key informants. Interview
      notes and focus group transcripts were then studied in-depth independently by
      three researchers. The primary analytic technique was constant comparison.
      RESULTS: One hundred twenty-nine subjects participated in this study: six focus
      groups (n=53) and 51 interviews among mothers, fathers, and grandparents, as well
      as 25 interviews among key informants. Main healthcare service obstacles to
      breastfeeding were erroneous information, lack of training and supervision,
      negative attitudes, miscommunication between healthcare providers (HCPs) and
      patients, detrimental medical practices such as giving free formula at hospitals,
      and the conflict of interest between the infant food industry and the HCPs.
      CONCLUSIONS: This study showed that women in low-income communities in Tijuana
      face multiple obstacles to breastfeeding presented by healthcare services. In
      order to increase breastfeeding rates, institutional and structural changes are
      required.

PMID- 25574872
TI  - Top Marathon performance: interesting debate and troubling trends.

PMID- 25574869
TI  - Neurokinin B is critical for normal timing of sexual maturation but dispensable
      for adult reproductive function in female mice.
AB  - Humans carrying mutations in neurokinin B (NKB) or the NKB receptor fail to
      undergo puberty due to decreased secretion of GnRH. Despite this pubertal delay,
      many of these patients go on to achieve activation of their hypothalamic
      pituitary-gonadal axis in adulthood, a phenomenon termed reversal, indicating
      that NKB signaling may play a more critical role for the timing of pubertal
      development than adult reproductive function. NKB receptor-deficient mice are
      hypogonadotropic but have no defects in the timing of sexual maturation. The
      current study has performed the first phenotypic evaluation of mice bearing
      mutations in Tac2, the gene encoding the NKB ligand, to determine whether they
      have impaired sexual development similar to their human counterparts. Male Tac2-/
      mice showed no difference in the timing of sexual maturation or fertility
      compared with wild-type littermates and were fertile. In contrast, Tac2-/-
      females had profound delays in sexual maturation, with time to vaginal opening
      and first estrus occurring significantly later than controls, and initial
      abnormalities in estrous cycles. However, cycling recovered in adulthood and Tac2
      /- females were fertile, although they produced fewer pups per litter. Thus,
      female Tac2-/- mice parallel humans harboring NKB pathway mutations, with delayed
      sexual maturation and activation of the reproductive cascade later in life.
      Moreover, direct comparison of NKB ligand and receptor-deficient females
      confirmed that only NKB ligand-deficient animals have delayed sexual maturation,
      suggesting that in the absence of the NKB receptor, NKB may regulate the timing
      of sexual maturation through other tachykinin receptors.

PMID- 25574874
TI  - Exercise can protect against a broken heart.

PMID- 25574875
TI  - Concussion in the absence of head impact: a case in a collegiate hammer thrower.

PMID- 25574877
TI  - Coexistent sports-related concussion and cervical SCIWORA in an adolescent: a
      case report.

PMID- 25574878
TI  - Duret hemorrhage after the seventh concussion in a high school football player: a
      case report.

PMID- 25574876
TI  - Occipital neuralgia as a sequela of sports concussion: a case series and review
      of the literature.

PMID- 25574879
TI  - Dental problems in athletes.
AB  - Orofacial injuries and diseases occur in athletes, and they may not always have
      access to dentists. Therefore team physicians should be aware of the common
      injuries and initial management. Treatment of dental injuries will depend on
      whether the teeth are primary or permanent. The most common type of fracture is
      crown fracture, but there are other dental injuries that can lead to future
      complications if not treated promptly and monitored closely. Tooth avulsions need
      to be handled properly, and athletes should see a dentist as soon as possible.
      Despite the urgency of some injuries, other orofacial injuries or diseases, such
      as lacerations and caries, should not be overlooked. Proper education and use of
      mouth guards can assist athletes in reducing their risk of orofacial injuries. 

PMID- 25574880
TI  - Thoracic spine sports-related injuries.
AB  - Although sports-related injuries to the thoracic spine are relatively uncommon,
      they are among the most feared due to the potential for catastrophic neurologic
      injury. The increased biomechanical support of the thoracic spine makes injuries
      in this region particularly rare compared with the cervical and lumbar spine. As
      a result, thoracic spine injuries can be missed easily, difficult to diagnose,
      and problematic to treat. Recognition of mechanism and awareness of injury
      patterns help physicians determine a diagnosis and create an index of suspicion
      for unstable thoracic spine injuries. Aggressive full-contact sports receive the
      most attention for spinal injury; however several sports with repetitive loading
      of the spine can cause severe injuries, including rowing, gymnastics, and golf.
      The goal of this article was to provide an overview of the unique anatomic and
      biomechanical features of the thoracic spine and to discuss some of the more
      common thoracic injuries that can affect athletes. 

PMID- 25574881
TI  - Piriformis syndrome: a cause of nondiscogenic sciatica.
AB  - Piriformis syndrome is a nondiscogenic cause of sciatica from compression of the
      sciatic nerve through or around the piriformis muscle. Patients typically have
      sciatica, buttocks pain, and worse pain with sitting. They usually have normal
      neurological examination results and negative straight leg raising test results.
      Flexion, adduction, and internal rotation of the hip, Freiberg sign, Pace sign,
      and direct palpation of the piriformis cause pain and may reproduce symptoms.
      Imaging and neurodiagnostic studies are typically normal and are used to rule out
      other etiologies for sciatica. Conservative treatment, including medication and
      physiotherapy, is usually helpful for the majority of patients. For recalcitrant
      cases, corticosteroid and botulinum toxin injections may be attempted. Ultrasound
      and other imaging modalities likely improve accuracy of injections. Piriformis
      tenotomy and decompression of the sciatic nerve can be done for those who do not
      respond. 

PMID- 25574882
TI  - Amyotrophic lateral sclerosis: the role of exercise.
AB  - Amyotrophic lateral sclerosis (ALS) is a chronic progressive neurodegenerative
      disease affecting both the upper and lower motor neurons. Given the deterioration
      of skeletal muscle function, historically there has been concern regarding
      exercise and its affect on ALS. This article reviews and explains current
      research, helping patients, caregivers, and providers be equipped better to make
      decisions regarding the treatment of ALS with exercise. 

PMID- 25574883
TI  - A football player with thrombocytopenia.

PMID- 25574884
TI  - Acute liver failure complicating exertional heat stroke: possible role of
      hypophosphatemia.

PMID- 25574885
TI  - Lyme disease in athletes.
AB  - Lyme disease, a bacterial infection transmitted by ticks, is the most common
      vector-borne disease in the northern hemisphere. Athletes who train or compete in
      wooded environments in endemic regions are at increased risk of contracting Lyme
      disease. Variability in clinical presentation, masquerading symptoms, and
      limitations in testing may lead to misdiagnosis. Early diagnosis and treatment
      result in full recovery for most patients with Lyme disease; however symptoms may
      persist for months to years, especially when diagnosis is delayed. This article
      reviews the epidemiology, clinical manifestations, diagnosis, treatment, and
      prevention of Lyme disease, with focus on the athletic population. 

PMID- 25574886
TI  - Depression in athletes: prevalence and risk factors.
AB  - Depression affects an estimated 6.7% of today's adult population in a 12-month
      period. The prevalence rates for certain age groups, such as young adults and
      older adults, are higher. There are approximately 400,000 National Collegiate
      Athletic Association student athletes competing each year and 5 to 7 million high
      school student athletes involved in competitive interscholastic sports. Given
      such a high prevalence rate in certain age groups and a large denominator pool of
      athletes, past notions that athletes are devoid of mental health issues have come
      under scrutiny by sports medicine providers. Initial data suggest that athletes
      are far from immune to depression. The purpose of this article was to review the
      current research on athletes and depression; particularly this article will
      provide an overview of studies, which have investigated the rate of depression
      among athletes, and discuss relevant risk factors, which may contribute to
      depression among athletes. 

PMID- 25574887
TI  - Cholinergic urticaria and exercise-induced anaphylaxis.
AB  - In this article, we will present the physical manifestations of two similar
      conditions. The first is cholinergic urticaria. This is chronic urticaria
      precipitated by an elevated body temperature. The second is exercise-induced
      anaphylaxis. Anaphylaxis can be idiopathic, a result of a specific allergenic
      trigger (food, medication, or insect sting), or exercise induced. We will focus
      on the third subtype. We describe the causes, symptoms, pathophysiology, testing,
      treatment, and prognosis of these two conditions. 

PMID- 25574888
TI  - Sepsis, septic shock, and fatal exertional heat stroke.
AB  - Exertional heat stroke (EHS) is a clinical syndrome of hyperthermia,
      encephalopathy, and multiorgan dysfunction that can be irreversible and fatal.
      While prompt recognition and immediate, aggressive total body cooling can prevent
      progression of the clinical syndrome, even a short delay can exacerbate the
      effects of hyperthermia-induced changes. EHS is linked to an inflammatory
      response that is akin to the systemic inflammatory response syndrome (SIRS).
      However because EHS is not a common problem in most hospital intensive care units
      and is not in the usual list of SIRS causes, it may be overlooked easily.
      Furthermore normalizing the body temperature of patients with EHS, especially
      when hyperthermia recognition and total body cooling are delayed, may not prevent
      SIRS and its clinical consequences. This narrative review focuses on the
      inflammatory response behind the pathway leading to EHS-associated organ
      pathology and recommends a new insight to possible clinical interventions beyond
      whole body cooling. 

PMID- 25574890
TI  - Ultrafiltration for congestive heart failure: the past and the present.
AB  - PURPOSE OF REVIEW: To provide an overview on the most recent evidence for the use
      of extracorporeal and peritoneal ultrafiltration in heart failure, focusing on
      the major publications from the last few years. RECENT FINDINGS: There have been
      several studies investigating the possible use of extracorporeal and peritoneal
      ultrafiltration in the management of acute and chronic heart failure. These
      trials have investigated the potential benefits and advantages of ultrafiltration
      over conventional medical therapy, in terms of clinical outcomes. SUMMARY:
      Although ultrafiltration remains an extremely appealing therapeutic option for
      patients with heart failure and congestion, with several theoretical beneficial
      effects, some of the most recent studies have reported inconsistent findings.
      Differences in the selection of the study population, heterogeneity of the
      indications for use of ultrafiltration, variation in the ultrafiltration
      protocols, and high variability in the pharmacologic therapy used for the control
      group could explain some of these conflicting findings.

PMID- 25574889
TI  - Pathophysiological characteristics and effects of obesity in women with early and
      late manifestation of gestational diabetes diagnosed by the International
      Association of Diabetes and Pregnancy Study Groups criteria.
AB  - CONTEXT: Appropriate risk stratification is essential in gestational diabetes
      (GDM) diagnosis to optimize therapeutic strategies during pregnancy. However,
      there are sparse data related to the newly recommended International Association
      of Diabetes and Pregnancy Study Groups criteria and their use in early pregnancy.
      OBJECTIVE: This study sought to evaluate clinical and pathophysiological
      characteristics less up to gestational week (GW) 21 in women with early and late
      GDM onset. DESIGN AND SETTING: This was a prospective study conducted at the
      Medical University of Vienna. PATIENTS AND INTERVENTIONS: Pregnant women (n =
      211) underwent an oral glucose tolerance test at 16 GW (interquartile range, 14
      18 wk) with multiple measurements of glucose, insulin, and C-peptide for
      evaluation of insulin sensitivity and beta-cell function in addition to detailed
      obstetrical risk assessment. Clinical followups were performed until end of
      pregnancy. MAIN OUTCOME MEASURE: We performed a metabolic characterization of
      early-onset GDM. RESULTS: Of 81 women, 49 (23%) showed early (GDMEarly <= 21 GW)
      and 32 (15%) later manifestation (GDMLate >= 24 GW) whereas 130 (62%) remained
      normal-glucose-tolerant (NGT). In contrast with GDMLate, GDMEarly were affected
      by decreased insulin sensitivity (GDMEarly vs NGT, P < .001; GDMEarlyvs GDMLate,
      P < .001; GDMLate vs NGT, P = .410). However, both early and late manifested
      subjects showed impairments in beta-cell function. GDMEarly showed highest levels
      of preconceptional and actual body mass index (BMI), which was related to fasting
      glucose (r = 0.42, P < .001) and particularly insulin sensitivity (r = -0.51, P <
      .001). Differences in glucose disposal between the subgroups remained constant in
      multivariable analysis including the strongest risk factors for GDM, ie, age,
      history of GDM, and BMI in our population. CONCLUSIONS: Early manifestation of
      GDM is affected by insulin resistance that is partly explained by higher degree
      in obesity. However, beta-cell dysfunction was also detectable in GDMLate,
      indicating defective compensatory mechanisms emerging already in early pregnancy.

PMID- 25574891
TI  - Gender differences in outcomes following cardiac surgery: implications for
      managing patients with mitral valve disease.
AB  - PURPOSE OF REVIEW: This review summarizes the differences in clinical outcomes
      following cardiac surgery according to gender. RECENT FINDINGS: Women comprise a
      large proportion of patients presenting with coronary artery or valvular heart
      disease. Although it is well known that women have poorer survival following
      bypass surgery compared with men, more recent data confirm that women also have
      poorer outcomes after heart valve surgery. Women are also more likely to receive
      mitral valve replacement instead of repair, when compared with men. These
      divergent outcomes are because of many factors, including valve disease and
      clinical presentation, which may result in delayed surgical referral in women.
      SUMMARY: Factors that result in poorer outcomes following heart valve surgery,
      including mitral valve surgery, between men and women remain incompletely
      understood. These may relate to differences in clinical presentation, valve
      morphology, and physiology. Further research is needed to clarify differences in
      heart valve outcomes according to gender.

PMID- 25574892
TI  - Edge-to-edge surgical mitral valve repair in the era of MitraClip: what if the
      annuloplasty ring is missed?
AB  - PURPOSE OF REVIEW: The purpose of this review is to define the role of
      annuloplasty in the surgical edge-to-edge repair, an issue that seems
      particularly relevant in the current MitraClip era, when more than 15 000
      patients have been submitted to a percutaneous transcatheter edge-to-edge repair
      without concomitant annuloplasty. RECENT FINDINGS: Only a few studies have
      reported the clinical and echocardiographic outcomes of the ringless edge-to-edge
      mitral repair. In all of them, however, only mid-term data were provided.
      Recently, the long-term results of the surgical edge-to-edge procedure performed
      without a concomitant annuloplasty in a selected group of patients with
      degenerative mitral regurgitation have been published. SUMMARY: The surgical edge
      to-edge technique should always be combined with prosthetic ring annuloplasty in
      order to provide excellent long-term outcomes in patients with degenerative
      mitral regurgitation. The overall long-term results of the surgical edge-to-edge
      technique without annuloplasty are not satisfactory. The ringless edge-to-edge
      technique is not effective in the challenging setting of extensively calcified
      annulus. In patients without annular calcification, in whom annuloplasty was
      intentionally avoided, the ringless edge-to-edge repair provides acceptable
      results in the mid term but is associated with a high failure rate in the long
      term. In the MitraClip perspective, these findings emphasize the need for a
      reliable annuloplasty to improve the long-term outcomes of the currently
      available transcatheter edge-to-edge procedure.

PMID- 25574893
TI  - Anticoagulation strategies for left ventricular assist devices.
AB  - PURPOSE OF REVIEW: Pump thrombosis can be a devastating complication in patients
      with a left ventricular assist device (LVAD). Treatment options with intravenous
      anticoagulation can lead to further complications. The present review discusses
      the current antithrombotic and anticoagulation strategies following LVAD
      implantation and during suspected pump thrombosis. RECENT FINDINGS: Recently, a
      significant increase in pump thrombosis (HeartMate II) at 3 months after LVAD
      implantation starting in March 2011 has been observed. This observation is likely
      multifaceted; however, recent changes in perioperative anticoagulation, accepting
      lower target international normalized ratios and lack of heparin bridging may
      play a substantial role. The International Society for Heart and Lung
      Transplantation published guidelines surrounding LVAD anticoagulation and
      management options in the setting of pump thrombosis. SUMMARY: Recommendations
      for thromboprophylaxis in patients with LVADs are scarce. The International
      Society for Heart and Lung Transplantation has put together minimum criteria for
      perioperative anticoagulation; however, this is on the basis of poor level of
      evidence (observational studies and expert opinion). Ultimately, clinicians will
      need to individualize the intensity and timing of anticoagulation following LVAD
      implantation to ensure adequate thromboprophylaxis while simultaneously
      minimizing bleeding.

PMID- 25574894
TI  - Evaluation, prevention and management of cancer therapy-induced cardiotoxicity: a
      contemporary approach for clinicians.
AB  - PURPOSE OF REVIEW: While targeted therapies have improved cancer outcomes, unique
      cardiovascular toxicities are increasingly recognized, particularly when
      administered sequentially after anthracyclines or radiation. Patients with cancer
      therapy-induced cardiotoxicity benefit from collaborative care involving
      cardiology and oncology, leading to a new interdisciplinary field called cardio
      oncology. The present review will highlight contemporary clinical issues in
      cardio-oncology. RECENT FINDINGS: Recently, risk factors for cancer therapy
      induced cardiotoxicity have been evaluated in real-world rather than in clinical
      trial patients. Biomarkers and advanced echocardiography are emerging as
      sensitive tools for preclinical identification of cancer therapy-induced
      cardiotoxicity. Single-center studies suggest that cancer therapy-induced
      cardiotoxicity responds to prompt heart failure medical treatment, and such
      therapy may even prevent cardiotoxicity. SUMMARY: Modern cancer therapy has short
      term cardiac risk that may require collaborative management by clinicians with
      expertise in cardiology and oncology. The increased effectiveness of modern
      cancer therapy is resulting in a growing population of cancer survivors who are
      at long-term risk for cardiovascular disease. The present review of contemporary
      clinical issues in cardio-oncology will be of interest to healthcare providers
      who manage cardiotoxicity during cancer therapy, and who follow patients who
      survive cancer but face increased long-term cardiovascular risk.

PMID- 25574895
TI  - Atrial fibrillation and heart failure: a bad combination.
AB  - PURPOSE OF REVIEW: Heart failure and atrial fibrillation are both common cardiac
      conditions that share multiple risk factors. Heart failure is a risk for atrial
      fibrillation and atrial fibrillation is a risk for heart failure. The need to
      understand the interplay between these two cardiac conditions and the
      effectiveness of management options becomes increasingly relevant. RECENT
      FINDINGS: Recent studies have focused on the prognostic nature of atrial
      fibrillation and heart failure, the questionable utility of digoxin and beta
      blocker therapy when heart failure and atrial fibrillation coexist, and the
      efficacy of cardiac ablation and resynchronization therapy with concomitant heart
      failure and atrial fibrillation. SUMMARY: The predominant questions that require
      further attention with respect to atrial fibrillation and heart failure are
      whether catheter ablation and rhythm control offers benefit in a high-risk heart
      failure population with respect to mortality or heart failure reduction, and
      whether cardiac resynchronization therapy implantation truly benefits the
      subgroup of candidate patients with permanent atrial fibrillation. Large
      randomized multicentre studies are currently ongoing to address these important
      questions.

PMID- 25574896
TI  - Evolving role for mineralocorticoid receptor antagonists in heart failure with
      preserved ejection fraction.
AB  - PURPOSE OF REVIEW: The majority of randomized clinical trials in heart failure
      with preserved ejection fraction (HFpEF) have failed to show meaningful
      improvements in clinical outcomes. Recent randomized trials have shown benefits
      from mineralocorticoid receptor antagonists (MRAs) in the management of HFpEF.
      This review will focus on new evidence for MRA therapy in patients with HFpEF.
      RECENT FINDINGS: Three randomized trials were reviewed: the Effect of
      spironolactone on diastolic function and exercise capacity in patients with heart
      failure with preserved ejection fraction: the Aldo-DHF randomized controlled
      trial; the Treatment of Preserved Cardiac Function Heart Failure with an
      Aldosterone Antagonist trial; and its echocardiography substudy. The Aldo-DHF
      trial showed improvements in echocardiographic measures of diastolic function. In
      the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone
      Antagonist trial, hospitalization for heart failure was significantly reduced
      with MRA therapy with no difference in the primary outcome of cardiovascular
      death or hospitalization. In patients with high risk, however, there may be a
      reduction in cardiovascular mortality. We will also briefly discuss finerenone, a
      new generation MRA associated with a lower incidence of hyperkalemia. SUMMARY:
      New evidence shows that MRA therapy decreases left ventricular mass and left
      atrial size, reduces hospitalization, and may reduce cardiovascular mortality in
      patients with high risk.

PMID- 25574897
TI  - Moderate mitral regurgitation at the time of coronary bypass surgery: repair or
      leave it?
AB  - PURPOSE OF REVIEW: Moderate ischemic mitral regurgitation (IMR) is a common
      finding in patients undergoing coronary artery bypass grafting (CABG). In this
      review, we summarize the current evidence on the optimal management of this
      condition. RECENT FINDINGS: In recent years, several randomized clinical trials
      have assessed the impact of concomitant restrictive mitral annuloplasty at the
      time of CABG on reverse left ventricular remodeling, IMR reduction and clinical
      outcomes. SUMMARY: Surgical revascularization alone is a conservative strategy
      that reduces IMR in a significant proportion of patients. Concomitant restrictive
      annuloplasty provides better relief of mitral regurgitation in the immediate
      postoperative period, at the cost of increased perioperative morbidity. The only
      major randomized trial on the issue of moderate IMR published to date showed no
      difference in reverse left ventricular remodeling at 1 year between these two
      approaches. There are insufficient data in the literature to support the routine
      addition of mitral valve repair to CABG in patients with moderate IMR.

PMID- 25574899
TI  - Correlation between NAT2 gene polymorphism and cirrhotic portal hypertension in
      the Chinese population.
AB  - BACKGROUND: Our study aims to discuss the correlation between N-acetyltransferase
      2 (NAT2) gene polymorphism and cirrhotic portal hypertension in the Chinese
      population for the purpose of exploring the functional significance of NAT2 gene
      polymorphism. METHODS: From June 2010 to February 2014, a total of 212
      posthepatitis B cirrhosis patients (the observation group) from the affiliated
      Shandong Province-owned Hospital of Shandong University diagnosed by needle
      biopsy of the liver, B ultrasound, or surgical operation were recruited. These
      212 patients were divided into a cirrhotic portal hypertension group (PHT(+)
      group) (130 patients) and a simple liver cirrhosis (LC) group (PHT(-) group) (82
      patients), and 172 healthy blood donors were enrolled into the control group. The
      polymerase chain reaction-restriction fragment length polymorphism method was
      adopted to detect NAT2 gene polymorphism and some related statistical analysis.
      RESULTS: In these 212 patients, four mutation alleles in the NAT2 gene (WT, M1,
      M2, and M3) were detected. The frequency of patients carrying NAT2 slow
      acetylator genotype in the observation group was higher than that in the control
      group, but there was no significant difference (p>0.05). However, there was a
      significant difference in the NAT2 slow acetylator genotype frequency between the
      PHT(+) group and the control group (p<0.05). The risk for the occurrence of PHT
      in NAT2 slow acetylator genotype carriers was more frequent than that in NAT2
      rapid acetylator genotype carriers. In addition, the diameters of the portal vein
      and splenic vein as well as spleen thickness in NAT2 rapid acetylator genotype
      were obviously bigger than that in the NAT2 slow acetylator genotype.
      CONCLUSIONS: Our study provided empirical evidence that NAT2 gene polymorphism
      may be correlated to the formation of cirrhotic portal hypertension, and it might
      be used as a potential biomarker for genetic susceptibility to PHT in Chinese
      population.

PMID- 25574900
TI  - Primary care management of celiac disease.
AB  - : Celiac disease is an autoimmune disorder with genetic predisposition that
      affects as many as 1 in 100 individuals. Treatment is a lifelong, strict
      adherence to a gluten-free diet. Management by a primary care provider may lead
      to increased adherence and can minimize effects of nonadherence to the diet. 

PMID- 25574898
TI  - Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of
      childhood blindness.
AB  - Blindness due to retinal degeneration affects millions of people worldwide, but
      many disease-causing mutations remain unknown. PNPLA6 encodes the patatin-like
      phospholipase domain containing protein 6, also known as neuropathy target
      esterase (NTE), which is the target of toxic organophosphates that induce human
      paralysis due to severe axonopathy of large neurons. Mutations in PNPLA6 also
      cause human spastic paraplegia characterized by motor neuron degeneration. Here
      we identify PNPLA6 mutations in childhood blindness in seven families with
      retinal degeneration, including Leber congenital amaurosis and Oliver McFarlane
      syndrome. PNPLA6 localizes mostly at the inner segment plasma membrane in
      photoreceptors and mutations in Drosophila PNPLA6 lead to photoreceptor cell
      death. We also report that lysophosphatidylcholine and lysophosphatidic acid
      levels are elevated in mutant Drosophila. These findings show a role for PNPLA6
      in photoreceptor survival and identify phospholipid metabolism as a potential
      therapeutic target for some forms of blindness. 

PMID- 25574901
TI  - Recognizing depression in late life.
AB  - Depression presents differently in older adults than in younger adults and
      frequently occurs with many chronic illnesses in later life, though it is not a
      normal part of aging. The astute practitioner will screen for depression in this
      population and appropriately treat to improve chronic illness management and
      quality of life in older adults.

PMID- 25574902
TI  - Reduced apparent diffusion coefficient in neuromyelitis optica-associated optic
      neuropathy.

PMID- 25574903
TI  - Polymorphisms associated with expression of BPIFA1/BPIFB1 and lung disease
      severity in cystic fibrosis.
AB  - BPI fold containing family A, member 1 (BPIFA1) and BPIFB1 are putative innate
      immune molecules expressed in the upper airways. Because of their hypothesized
      roles in airway defense, these molecules may contribute to lung disease severity
      in cystic fibrosis (CF). We interrogated BPIFA1/BPIFB1 single-nucleotide
      polymorphisms in data from an association study of CF modifier genes and found an
      association of the G allele of rs1078761 with increased lung disease severity (P
      = 2.71 * 10(-4)). We hypothesized that the G allele of rs1078761 is associated
      with decreased expression of BPIFA1 and/or BPIFB1. Genome-wide lung gene
      expression and genotyping data from 1,111 individuals with lung disease,
      including 51 patients with CF, were tested for associations between genotype and
      BPIFA1 and BPIFB1 gene expression levels. Findings were validated by quantitative
      PCR in a subset of 77 individuals. Western blotting was used to measure BPIFA1
      and BPIFB1 protein levels in 93 lung and 101 saliva samples. The G allele of
      rs1078761 was significantly associated with decreased mRNA levels of BPIFA1 (P =
      4.08 * 10(-15)) and BPIFB1 (P = 0.0314). These findings were confirmed with
      quantitative PCR and Western blotting. We conclude that the G allele of rs1078761
      may be detrimental to lung function in CF owing to decreased levels of BPIFA1 and
      BPIFB1. 

PMID- 25574905
TI  - Knowledge, attitudes and beliefs of technical staff towards doping in Spanish
      football.
AB  - The aim of this study was to understand the attitudes, beliefs and knowledge
      among technical staff members of Spanish football teams regarding doping. The
      sample was drawn from 88 football teams that ranged from elite to under-18
      categories. The 237 stakeholders (34.45 +/- 8.59 years) were categorised as
      follows: coaches (COA) (n = 101), physical trainers (PT) (n = 68) and rest of
      technical staff (RTS) (n = 68). The descriptive exploratory design used an
      instrument that combined a validated questionnaire (Performance Enhancement
      Attitude Scale; PEAS) with specific, qualitative open-ended questions. The
      overall mean score from the PEAS (range, 17-102, with higher scores representing
      more permissive attitudes towards doping) was 31.64 +/- 10.77; for COA, 31.91 +/-
      11.42; for PT, 31.28 +/- 9.44; and for RTS, 31.58 +/- 11.18. Regarding
      participants' knowledge and beliefs, most respondents (57.6%) did not know the
      meaning of WADA (World Anti-Doping Agency); 84.9% did not know the prohibited
      list; and 39.2% had used/recommended supplements. In addition, 87.2% recognised
      "differential treatment of doping among sports," with cycling considered most
      affected (62.6%) and team sports least (27.2%, with football at 15%). The
      dangerous lack of knowledge highlights the necessity for anti-doping education
      and prevention programs for all football stakeholders, not just athletes. 

PMID- 25574904
TI  - Mailuoning for acute ischaemic stroke.
AB  - BACKGROUND: Mailuoning is widely used in the treatment of acute ischaemic stroke
      in China. Animal experimental studies and clinical pharmacological research
      indicate that mailuoning might improve blood circulation, prevent ischaemic
      injury, and protect heart and brain tissue. This review was last published in
      2009. As new data have become available, it is necessary to reassess the evidence
      from randomised controlled trials. OBJECTIVES: To determine the effects and
      safety of mailuoning agents (injection or oral liquid) in the treatment of people
      with acute ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke
      Group Trials Register (May 2014), the Cochrane Central Register of Controlled
      Trials (CENTRAL;2014, Issue 4), MEDLINE (1966 to May 2014), Embase (1980 to May
      2014), AMED (1985 to May 2014), the Chinese Stroke Trials Register (June 2014),
      the China Biological Medicine Database (CBM-disc; 1979 to June 2014), China
      Science and Technology Journal database (CSTJ; 1979 to June 2014), Wanfang Data
      Chinese databases (1979 to June 2014), and the China National Knowledge
      Infrastructure (1979 to June 2014). We searched clinical trials and research
      registers, handsearched 10 Chinese journals including relevant conference
      proceedings, scanned reference lists, and contacted the pharmaceutical company
      that manufactures mailuoning. We also attempted to contact trial authors to
      obtain further data. SELECTION CRITERIA: Randomised controlled trials comparing
      mailuoning with placebo or mailuoning plus other treatment compared with that
      other treatment in people with acute ischaemic stroke. DATA COLLECTION AND
      ANALYSIS: Two review authors independently selected trials for inclusion,
      assessed trial quality, and extracted data. MAIN RESULTS: We included 21 trials,
      involving 1746 participants, in this update; six trials were new. The included
      trials did not report the numbers of dead and dependent participants at the end
      of at least three months' follow-up. Of the 12 trials that reported adverse
      events, five events occurred in two trials. There was no significant difference
      between the treatment group and the control group. We assessed 20 trials to be of
      a poor quality: When analysing these trials together, mailuoning was associated
      with a significant increase in the number of participants with an improved
      neurological deficit (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.23 to
      0.42) and showed a significant improvement of neurological deficit with the
      European Stroke Scale (ESS) (mean difference (MD) (fixed) 8.29, 95% CI 3.44 to
      13.15). One placebo-controlled trial, assessed to be of a better methodological
      quality, failed to show a significant improvement of neurological deficit at the
      end of three months' follow-up (MD (fixed) 2.49, 95% CI -1.45 to 6.43) or in
      quality of life. One trial, which reported cognitive function using the Montreal
      Cognitive Assessment as a continuous scale, showed a significant improvement of
      cognitive function (MD (fixed) 2.68, 95% CI 1.82 to 3.54). Two trials assessed
      activities of daily life: One trial showed a significant improvement, but the
      other did not. AUTHORS' CONCLUSIONS: This review did not provide sufficient
      evidence to support the routine use of mailuoning for the treatment of people
      with acute ischaemic stroke. High-quality large-scale randomised controlled
      trials are needed to confirm the efficacy of mailuoning.

PMID- 25574906
TI  - Treating multidrug-resistant tuberculosis in community settings: a wise
      investment.

PMID- 25574907
TI  - Rapid molecular detection of pyrazinamide resistance: the way forward.

PMID- 25574908
TI  - Management of asthma in resource-limited settings: role of low-cost
      corticosteroid/beta-agonist combination inhaler.
AB  - The management of asthma requires medicines that are effective in relaxing airway
      smooth muscles and in reducing airway inflammation. Rapid-acting beta2 agonist is
      a bronchodilator that provides quick symptom relief in patients with asthma.
      However, it does not effectively address the underlying problem of airway
      inflammation. Excess use of inhaled bronchodilators alone for symptom relief may
      result in delay in seeking health care, which in turn may result in delayed use
      of anti-inflammatory agents. Inhaled corticosteroid (ICS) is critical in the
      treatment of airway inflammation; it reduces the risk of life-threatening asthma
      attacks and the need for hospitalisation. ICS is underused, however, and a
      substantial proportion of patients with persistent asthma in resource-limited
      settings have no access to affordable ICS for long-term treatment. International
      guidelines recommend the use of rapid-acting beta-agonists as needed as rescue
      treatment when symptoms occur. Studies have shown that the use of both ICS and
      rapid-acting beta-agonist as needed for symptom relief might be a better option.
      The combination of ICS and rapid-acting bronchodilator in a single inhaler is
      currently too expensive and is not affordable for the poor. Although ICS and
      short-acting beta2 agonist (SABA) for rescue treatment can be obtained to a
      certain extent by using separate ICS and SABA inhalers, the first step is to
      ensure access to affordable, quality-assured essential asthma medicine in
      resource-limited settings.

PMID- 25574909
TI  - Latent tuberculous infection: ethical considerations in formulating public health
      policy.
AB  - There is increasing interest in the introduction of public health policies
      relating to latent tuberculous infection (LTBI). However, there has been little
      previous systematic engagement with LTBI from an ethical perspective. This
      article offers a general overview of ethical issues in relation to LTBI, with
      particular focus on those aspects relevant to the development and implementation
      of public health policy. Key characteristics of LTBI are discussed from an
      ethical perspective, with examples of challenging situations for policy makers. 

PMID- 25574910
TI  - Tuberculosis interferon-gamma responses in the breast milk of human
      immunodeficiency virus infected mothers.
AB  - Tuberculosis (TB) cellular immune responses were examined in the breast milk of
      human immunodeficiency virus infected mothers using the T-SPOT. TB interferon
      gamma release assay (IGRA). Positive TB interferon-gamma (IFN-gamma) responses
      were detected in 6 of 8 (75%) valid breast milk assays. Among 7 mothers with
      paired breast milk and blood assays, TB IFN-gamma responses were higher in breast
      milk than in blood (P = 0.02). The magnitude of TB IFN-gamma responses in
      maternal breast milk and blood were correlated. Elucidating the influence of TB
      immune responses in breast milk on infant TB susceptibility and immunity may
      inform future maternal TB vaccine strategies.

PMID- 25574911
TI  - Markers to differentiate between Kaposi's sarcoma and tuberculous pleural
      effusions in HIV-positive patients.
AB  - BACKGROUND: Kaposi's sarcoma (KS) and tuberculosis (TB) commonly cause pleural
      effusions in high human immunodeficiency virus (HIV) burden resource-limited
      countries. Differentiating between them is challenging, as pleural biopsy and TB
      culture are rarely available. OBJECTIVES: To identify markers to differentiate
      between TB effusions and KS effusions in HIV-positive patients, and to compare
      liquid culture and Xpert MTB/RIF in pleural fluid. METHODS: Fifty HIV-positive
      patients with pleural effusions recruited in Malawi underwent pleural ultrasound
      and aspiration. Fluid visual inspection, cell count, bacterial culture,
      glucose/protein, solid and liquid TB culture and Xpert were performed. RESULTS:
      The mean age of the patients was 32 years; 30/50 (60%) were male and 29 (58%) had
      cutaneous/oral KS. Thirteen (26%) pleural fluid samples were liquid culture
      positive for TB, while 9/13 (69%) were Xpert-positive. Three (10.3%) KS patients
      had culture-positive TB effusions; 17 (58.6%) had KS effusions. The relative risk
      of TB in KS patients increased with limited KS, loculated fluid and low glucose.
      Eleven (52.3%) non-KS patients had culture-positive TB effusions associated with
      male sex, straw-coloured fluid and fibrin stranding on ultrasound. CONCLUSIONS:
      KS patients were most likely to have KS effusion, but TB should be considered.
      Most non-KS patients had TB, supporting the use of World Health Organization
      guidelines. Xpert identified two thirds of liquid culture-positive results.

PMID- 25574912
TI  - Anti-tuberculosis drug resistance in Bangladesh: reflections from the first
      nationwide survey.
AB  - OBJECTIVE: To determine the prevalence of tuberculosis (TB) drug resistance in
      Bangladesh. DESIGN: Weighted cluster sampling among smear-positive cases, and
      standard culture and drug susceptibility testing on solid medium were used.
      RESULTS: Of 1480 patients enrolled during 2011, 12 falsified multidrug-resistant
      TB (MDR-TB) patients were excluded. Analysis included 1340 cases (90.5% of those
      enrolled) with valid results and known treatment antecedents. Of 1049 new cases,
      12.3% (95%CI 9.3-16.1) had strains resistant to any of the first-line drugs
      tested, and 1.4% (95%CI 0.7-2.5) were MDR-TB. Among the 291 previously treated
      cases, this was respectively 43.2% (95%CI 37.1-49.5) and 28.5% (95%CI 23.5-34.1).
      History of previous anti-tuberculosis treatment was the only predictive factor
      for first-line drug resistance (OR 34.9). Among the MDR-TB patients, 19.2% (95%CI
      11.3-30.5; exclusively previously treated) also showed resistance to ofloxacin.
      Resistance to kanamycin was not detected. CONCLUSION: Although MDR-TB prevalence
      was relatively low, transmission of MDR-TB may be increasing in Bangladesh. MDR
      TB with fluoroquinolone resistance is rapidly rising. Integrating the private
      sector should be made high priority given the excessive proportion of MDR-TB
      retreatment cases in large cities. TB control programmes and donors should avoid
      applying undue pressure towards meeting global targets, which can lead to
      corruption of data even in national surveys.

PMID- 25574913
TI  - Nationwide survey of anti-tuberculosis drug resistance in Japan.
AB  - OBJECTIVE: To determine the prevalence of anti-tuberculosis drug resistance in
      Japan. DESIGN: A nationwide drug resistance survey was conducted by convenience
      sampling based on a voluntary hospital consortium. Mycobacterium tuberculosis
      isolates (n = 2292) were collected from August 2007 to July 2008. Drug
      susceptibilities were analysed according to the patients' treatment history, age,
      sex, comorbidities and residential area. We determined susceptibility to the
      following drugs: isoniazid (INH), rifampicin (RMP), streptomycin (SM), ethambutol
      (EMB) and levofloxacin (LVX). RESULTS: The frequencies of drug-resistant isolates
      from new cases were as follows: INH, 3.1%; RMP, 0.7%; SM, 5.6%; EMB, 1.3%; and
      8.5% to any drug. The frequencies of drug-resistant isolates from previously
      treated patients were as follows: INH, 12.3%; RMP, 6.7%; SM, 12.3%; and EMB,
      2.6%. The frequencies of LVX-resistant isolates from new and previously treated
      patients were respectively 3.2% and 6.1% (n = 852). The frequencies of multidrug
      resistant isolates from new and previously treated patients were respectively
      0.4% and 4.1%, with only one extensively drug-resistant case. CONCLUSION: In
      general, the prevalence of drug-resistant TB in Japan during this period was low.
      However, LVX resistance among new patients was relatively high. Japan should
      establish a nationwide surveillance system.

PMID- 25574915
TI  - Impact of reduced hospitalisation on the cost of treatment for drug-resistant
      tuberculosis in South Africa.
AB  - SETTING: The cost of multidrug-resistant tuberculosis (MDR-TB) treatment is a
      major barrier to treatment scale-up in South Africa. OBJECTIVE: To estimate and
      compare the cost of treatment for rifampicin-resistant tuberculosis (RR-TB) in
      South Africa in different models of care in different settings. DESIGN: We
      estimated the costs of different models of care with varying levels of
      hospitalisation. These costs were used to calculate the total cost of treating
      all diagnosed cases of RR-TB in South Africa, and to estimate the budget impact
      of adopting a fully or partially decentralised model vs. a fully hospitalised
      model. RESULTS: The fully hospitalised model was 42% more costly than the fully
      decentralised model (US$13,432 vs. US$7753 per patient). A much shorter hospital
      stay in the decentralised models of care (44-57 days), compared to 128 days of
      hospitalisation in the fully hospitalised model, was the key contributor to the
      reduced cost of treatment. The annual total cost of treating all diagnosed cases
      ranged from US$110 million in the fully decentralised model to US$190 million in
      the fully hospitalised model. CONCLUSION: Following a more decentralised approach
      for treating RR-TB patients could potentially improve the affordability of RR-TB
      treatment in South Africa.

PMID- 25574914
TI  - Community-based care vs. centralised hospitalisation for MDR-TB patients, KwaZulu
      Natal, South Africa.
AB  - SETTING: KwaZulu-Natal, South Africa, a predominantly rural province with a high
      burden of tuberculosis (TB), multidrug-resistant TB (MDR-TB) and human
      immunodeficiency virus (HIV) infection. OBJECTIVE: To determine the most
      effective care model by comparing MDR-TB treatment outcomes at community-based
      sites with traditional care at a central, specialised hospital. DESIGN: A non
      randomised observational prospective cohort study comparing community-based and
      centralised care. Patients at community-based sites were closer to home and had
      easier access to care, and home-based care was available from treatment
      initiation. RESULTS: Four community-based sites treated 736 patients, while 813
      were treated at the centralised hospital (total = 1549 patients). Overall, 75%
      were HIV co-infected (community: 76% vs. hospitalised: 73%, P = 0.45) and 86%
      received antiretroviral therapy (community: 91% vs. hospitalised: 82%, P = 0.22).
      On multivariate analysis, MDR-TB patients were more likely to have a successful
      treatment outcome if they were treated at a community-based site (adjusted OR
      1.43, P = 0.01). However, outcomes at the four community-based sites were
      heterogeneous, with Site 1 demonstrating that home-based care was associated with
      an increased treatment success of 72% compared with success rates of 52-60% at
      the other three sites. CONCLUSION: Community-based care for MDR-TB patients was
      more effective than care in a central, specialised hospital. Home-based care
      further increased treatment success.

PMID- 25574916
TI  - Mutations in the pncA and rpsA genes among 77 Mycobacterium tuberculosis isolates
      in Kazakhstan.
AB  - SETTING: Pyrazinamide (PZA), an important first-line drug for anti-tuberculosis
      treatment, demonstrates potent activity against semi-dormant bacilli in acidic
      environments. However, the diagnosis of PZA resistance is often impeded by
      technical difficulties. OBJECTIVE: To characterise mutations in the pncA and rpsA
      genes among PZA-resistant and PZA-susceptible clinical Mycobacterium tuberculosis
      isolates circulating in Kazakhstan. The potential use of genotyping to identify
      PZA resistance was also investigated. DESIGN: PZA drug susceptibility testing and
      pncA and rpsA gene sequencing were performed on 77 clinical M. tuberculosis
      isolates; mycobacterial interspersed repetitive unit-variable number tandem
      repeat (MIRU-VNTR) typing was performed on 74 clinical M. tuberculosis isolates.
      RESULTS: Of the 77 clinical M. tuberculosis isolates, 41 (53.2%) were
      phenotypically resistant to PZA, whereas 36 (46.7%) were susceptible; 48 (62.3%)
      of these isolates were also multidrug-resistant (MDR). Furthermore, 38 (49.3%)
      clinical isolates showed mutations in the pncA gene and its flanking region; the
      majority of these isolates (n = 36, 94.7%) were also MDR. Gene sequencing showed
      that only synonymous substitutions affecting rpsA occurred. MIRU-VNTR typing
      revealed that 78.4% of isolates were of the Beijing genotype. CONCLUSIONS:
      Sequencing revealed that mutations in pncA, but not in rpsA, occurred in PZA
      resistant M. tuberculosis isolates circulating in the territory of Kazakhstan.

PMID- 25574918
TI  - CXCR3 ligands as clinical markers for pulmonary tuberculosis.
AB  - SETTING: A tertiary care academic medical centre. OBJECTIVE: To evaluate the
      clinical usefulness of CXC chemokine receptor 3 (CXCR3) ligands in active
      pulmonary tuberculosis (TB). DESIGN: Patients with various pulmonary diseases and
      healthy controls were recruited into this cross-sectional study. Plasma levels of
      interferon-gamma (IFN-gamma) and the CXCR3 ligands (CXCL9 [monokine induced by
      IFN-gamma, MIG], CXCL10 [IFN-gamma-inducible 10-kDa protein, IP-10] and CXCL11
      [IFN-inducible T-cell alpha chemoattractant, I-TAC] were measured using enzyme
      immunoassays. RESULTS: The study included 846 subjects: 201 patients with active
      pulmonary TB, 389 with other pulmonary diseases, and 256 controls. CXCR3 ligand
      levels were higher in TB patients than in controls and all other disease groups,
      whereas the IFN-gamma levels did not differ. The area under the curve (AUC) for
      differentiating active TB from all other groups was 0.797 for CXCL9, 0.726 for
      CXCL10, 0.846 for CXCL11 and 0.534 for IFN-gamma. The AUC for differentiating
      active TB from controls was 0.926 for CXCL9, 0.818 for CXCL10, 0.865 for CXCL11
      and 0.575 for IFN-gamma. CXCR3 levels correlated with sputum acid-fast bacilli
      smear grades and the radiographic extent of pulmonary TB. CONCLUSION: CXCR3
      ligands may be useful surrogate markers for diagnosing active TB and for
      assessing TB patients clinically.

PMID- 25574917
TI  - Disputed rpoB mutations can frequently cause important rifampicin resistance
      among new tuberculosis patients.
AB  - SETTING: Greater Mymensingh area, Bangladesh. OBJECTIVES: To document among new
      tuberculosis (TB) patients the proportions and treatment outcomes of silent, non
      disputed and disputed (generally missed by rapid drug susceptibility testing
      [DST]) rpoB mutations, and their detection by commercial molecular assays.
      DESIGN: Retrospective analysis of rpoB sequences from randomly selected ethanol
      preserved diagnostic sputum samples; comparison of sequencing with conventional
      DST results and standard first-line treatment outcome; retesting of samples with
      mutations using the Xpert MTB/RIF and GenoType MTBDRplus assays. RESULTS: Of 1091
      samples, 5.8% failed amplification, and six contained other mycobacteria. In 2005
      and 2010, respectively 2/500 (0.4%) and 11/522 (2.1%) amplicons showed non-silent
      mutations. At least 7/13 of these belonged to the disputed group, with 5/7
      patients suffering adverse treatment outcome. One silent mutation went undetected
      by commercial assays. Following routine DST indications, only three cases with a
      non-silent mutation were eventually detected. CONCLUSIONS: Disputed rpoB
      mutations may be responsible for the majority of rifampicin (RMP) resistance
      among new cases, and lead to adverse outcomes of first-line treatment. Silent
      mutations do not necessarily cause Xpert or line-probe assay false RMP-resistant
      results. Molecular RMP DST could greatly simplify resistance surveillance, in
      addition to offering the best prospects for early and accurate individual
      diagnosis.

PMID- 25574919
TI  - Chest radiograph findings in children with tuberculous meningitis.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is diagnosed based on a combination of
      clinical, laboratory and radiological findings, including signs suggestive of
      tuberculosis (TB) on a standard chest X-ray (CXR). METHODS: We describe the
      radiological features suggestive of intrathoracic TB in children diagnosed with
      TBM during a prospective evaluation of TBM suspects seen at Tygerberg Children's
      Hospital, Cape Town, South Africa. RESULTS: Of 84 children treated for TBM, 31
      (37%) had 'definite' TBM, 45 (55%) 'probable' TBM and 8 (9%) 'possible' TBM. In
      total, 37 (44%) TBM patients had CXR findings suggestive of TB, 9 (11%) with
      disseminated (miliary) TB. Only 1 in 4.39 children aged <=3 years with TBM had
      suggestive CXR findings. The presence of complicated intrathoracic lymph node
      disease was significantly higher in children aged <=3 years (OR 21.69, 95%CI 2.73
      172.67, P < 0.01). Among 6 human immunodeficiency virus infected children, 3
      (50%) had intrathoracic lymphadenopathy. CONCLUSION: The majority of the children
      with TBM, including the very young, did not have signs suggestive of TB on CXR.

PMID- 25574920
TI  - Survey of French physician practices in treatment and control of transmission of
      smear-positive tuberculosis.
AB  - OBJECTIVES: To evaluate isolation practices and management of sputum smear
      positive tuberculosis (TB) in France. METHODS: A survey was conducted using a
      questionnaire e-mailed in 2011 and 2012 to physicians of the French Society of
      Infectious Diseases, the French Respiratory Society and the French National
      Society of Internal Medicine. RESULTS: Of 311 responders, a quarter stated they
      treated more than 25 TB cases per year. A total of 87.8% declared they routinely
      used a four-drug regimen in the initial intensive phase. Of the 311 physicians
      who responded, 31.9% removed isolation precautions after three negative acid-fast
      bacilli (AFB) sputum results, 19.0% after 15 days of treatment and 34.1% only in
      case of clinical improvement. According to 71% of the responders, discharge from
      hospital despite positive AFB sputum smear results was 'possible'. A routine AFB
      sputum smear was performed after 2 months of treatment by only 21% of the
      responders. CONCLUSION: Despite recent national guidelines, the management of
      isolation precautions for sputum smear-positive TB remains heterogeneous, and a
      significant proportion of physicians use a three-drug regimen. Further efforts
      should be made to implement TB guidelines, mainly by raising awareness through
      national scientific institutions, but also by obtaining better evidence.

PMID- 25574921
TI  - Serum drug concentrations of INH and RMP predict 2-month sputum culture results
      in tuberculosis patients.
AB  - BACKGROUND: In Alberta provincial tuberculosis (TB) clinics, serum drug
      concentrations (SDCs) are measured in patients with human immunodeficiency virus,
      diabetes mellitus or at extremes of weight, or showing slow clinical response to
      treatment, to guide treatment. DESIGN: A retrospective review was performed of TB
      cases in Northern Alberta with SDCs measured from 1998 to 2013. Adequacy of SDC
      was based on the maximum concentration (Cmax) achieved in serum, with rifampicin
      (RMP) values <8 MUg/ml and isoniazid (INH) values <3 MUg/ml for daily dosing and
      <9 MUg/ml for intermittent dosing considered inadequate. Clinical variables and
      microbiological outcomes were then compared between the adequate and inadequate
      groups. RESULTS: Of 134 pulmonary TB cases with SDCs for INH and/or RMP, we found
      a significant increase in 2-month sputum culture positivity in the cohort with
      inadequate concentrations of INH compared to those with adequate INH
      concentrations (42.5% vs. 18.3%, P = 0.0084). A similar trend was seen in the
      cohort with inadequate concentrations of RMP (39% vs. 21%, P = 0.0725).
      CONCLUSIONS: Among our study population, low SDCs of INH and, to a lesser extent,
      RMP, appear to be associated with reduced sputum culture conversion after 2
      months of treatment.

PMID- 25574922
TI  - Market assessment of tuberculosis diagnostics in South Africa, 2012-2013.
AB  - OBJECTIVE: To assess the current served available market of tuberculosis (TB)
      diagnostics in South Africa in the public and private sectors. DESIGN: Public and
      private sector test volumes and unit costs were collected for tuberculin skin
      tests, interferon-gamma release assays, smear microscopy, culture, speciation,
      Xpert MTB/RIF, other nucleic acid amplification tests, drug susceptibility
      testing and adenosine deaminase tests. RESULTS: In 2012, during Xpert scale-up,
      the public and private sectors performed a total of 9.2 million TB diagnostic
      tests, at an estimated total value of US$98 million. The public sector accounted
      for 93% of the overall test volume and value. There were no major differences in
      the types of tests performed in both sectors, with microscopy and culture
      accounting for the majority of tests performed (72%). In 2013, the public sector
      market value increased to US$101 million (a 10% increase over 2012): Xpert
      volumes increased by 166%, while total TB test volumes decreased by 12% compared
      to 2012. CONCLUSION: South Africa has a substantial TB diagnostic market in terms
      of both volume and value. The roll-out of Xpert provides insights into how
      markets change in volume and value with the introduction of new tools.

PMID- 25574923
TI  - Quality of life of a migrant population with tuberculosis in West China.
AB  - OBJECTIVE: To describe the quality of life (QOL) of the migrant population with
      pulmonary tuberculosis (PTB) in West China, and identify factors associated with
      QOL. METHODS: A pilot investigation was conducted among 103 migrant individuals
      with PTB in Nanchong Region, Sichuan Province, China. The QOL and social support
      of the patients were investigated using a short version of the World Health
      Organization Quality of Life questionnaire and the Social Support Rating Scale,
      respectively. RESULTS: The mean scores of the QOL of the migrant population were
      respectively 12.1, 12.9 and 11.7 for the physical, psychological and
      environmental domains; these were significantly lower than those of the general
      Chinese population. Non-parametric tests detected the significant effects of the
      following: 1) educational levels on all domains, including social relationship;
      2) age on all domains, except psychological; 3) personal income on the physical
      and environmental domains; and 4) subjective support on all domains, except
      psychological. Multivariate logistic regression analyses confirmed that
      educational levels and subjective support were significantly associated with the
      global health status of the migrant population. CONCLUSIONS: The QOL of patients
      with TB among the migrant population in West China was poor; education and
      subjective support were important influential factors.

PMID- 25574924
TI  - Tuberculosis misclassification among resettled refugees in Buffalo, New York,
      USA.
AB  - BACKGROUND: Discordance in the classification of tuberculosis (TB) disease
      overseas compared to classification in the United States has been observed among
      immigrant populations. OBJECTIVE: To examine TB misclassification among recently
      resettled refugees in Buffalo, NY, between 2005 and 2012. METHODS: Retrospective
      study of refugees resettled to Buffalo from 2005 to 2012 and evaluated at a
      refugee/community health center. Centers for Disease Control and Prevention (CDC)
      Division of Global Migration and Quarantine (DGMQ) Class B1-B3 and American
      Thoracic Society (ATS) Class 2 (LTBI) cases were abstracted. Independent
      variables were demographics, countries of origin and refugee camp internment,
      year of resettlement, purified protein derivative induration, and chest X-ray
      findings, while CDC DGMQ and ATS classification were dependent variables.
      Independent samples t-test and analysis of variance were performed. RESULTS: Of
      284 charts reviewed, 233 (81.2%) were misclassified. Among 101 cases of LTBI
      (B1/B2) diagnosed outside the United States, 51 (50.5%) were overdiagnosed.
      Underdiagnoses occurred among 181/182 refugees (99.5%) originally classified as
      normal overseas. CONCLUSION: These findings suggest that TB misclassification
      among recent immigrants remains widespread. Screening procedures both before and
      after resettlement should be better synchronized. Public health implications
      range from morbidity and costs of unnecessary treatment to the spread of a highly
      communicable disease.

PMID- 25574925
TI  - Tuberculosis patients learning about second-hand smoke (TBLASS): results of a
      pilot randomised controlled trial.
AB  - BACKGROUND: Passive smoking is associated with tuberculosis (TB). Measures are
      required to protect non-smoking TB patients from second-hand smoke (SHS).
      SETTING: We developed a behavioural intervention to encourage TB patients to
      implement smoking restrictions at home in Pakistan. OBJECTIVES: To assess the
      likelihood of such an intervention being successful and to inform a definitive
      trial in future. DESIGN: This was a pilot randomised controlled trial in which
      non-smoking TB patients were randomised to receive either individual-based
      support or individual-based support combined with family reminders. We recruited
      patients living with at least one smoker in their homes. Our primary outcome was
      urinary cotinine level as a measure of SHS exposure 2 months post-randomisation.
      RESULTS: Of 273 patients assessed for eligibility, 150 (56%) patients were
      recruited and all but one were retained throughout the trial. A statistically
      significant absolute reduction was observed in non-smoking participants' exposure
      to SHS based on urinary cotinine levels in both Arm 1 (71%, 95%CI 61-79) and Arm
      2 (76%, 95%CI 67-83) between baseline and follow-up at 2 months. CONCLUSIONS: The
      recruitment and retention rates for trial participants make it feasible to
      conduct a definitive trial in future. The observed effect size makes it
      worthwhile to conduct such a trial.

PMID- 25574927
TI  - Mass treatment to eliminate tuberculosis from an island population.

PMID- 25574926
TI  - Occupational exposures associated with severe exacerbation of asthma.
AB  - BACKGROUND: The exacerbation of asthma by workplace conditions is common, but
      little is known about which agents pose a risk. OBJECTIVE: We used data from an
      existing survey of adults with asthma to identify occupational exposures
      associated with severe exacerbation of asthma. DESIGN: Questionnaires were
      completed by 557 working adults with asthma. Severe exacerbation of asthma in the
      past 12 months was defined as asthma-related hospitalization, or reports of both
      unplanned asthma care and treatment with a short course of oral corticosteroids.
      Occupational exposures for the same time period were assessed using an asthma
      specific job exposure matrix. We modeled severe exacerbation to yield prevalence
      ratios (PRs) for exposures while controlling for potential confounders. RESULTS:
      A total of 164 participants (29%) were positive for severe exacerbation, and 227
      (40.8%) were assessed as being exposed to asthma agents at work. Elevated PRs
      were observed for several specific agents, notably the irritant subcategories of
      environmental tobacco smoke (PR 1.84, 95%CI 1.34-2.51) among all participants,
      inorganic dusts (PR 2.53, 95%CI 1.37-4.67) among men, and the low molecular
      weight subcategory of other highly reactive agents (PR 1.97, 95%CI 1.08-3.60)
      among women. CONCLUSION: Among working adults with asthma, severe exacerbation
      was associated with several occupational agents.

PMID- 25574928
TI  - Breaking down barriers to adherence to standards of tuberculosis care.

PMID- 25574930
TI  - Global pattern for the effect of climate and land cover on water yield.
AB  - Research results on the effects of land cover change on water resources vary
      greatly and the topic remains controversial. Here we use published data worldwide
      to examine the validity of Fuh's equation, which relates annual water yield (R)
      to a wetness index (precipitation/potential evapotranspiration; P/PET) and
      watershed characteristics (m). We identify two critical values at P/PET=1 and
      m=2. m plays a more important role than P/PET when m<2, and a lesser role when
      m>2. When P/PET<1, the relative water yield (R/P) is more responsive to changes
      in m than it is when P/PET>1, suggesting that any land cover changes in non-humid
      regions (P/PET<1) or in watersheds of low water retention capacity (m<2) can lead
      to greater hydrological responses. m significantly correlates with forest
      coverage, watershed slope and watershed area. This global pattern has far
      reaching significance in studying and managing hydrological responses to land
      cover and climate changes. 

PMID- 25574931
TI  - Corrigendum: The tumour suppressor LKB1 regulates myelination through
      mitochondrial metabolism.

PMID- 25574932
TI  - Hydrogen peroxide displacing DNA from nanoceria: mechanism and detection of
      glucose in serum.
AB  - Hydrogen peroxide (H2O2) is a key molecule in biology. As a byproduct of many
      enzymatic reactions, H2O2 is also a popular biosensor target. Recently,
      interfacing H2O2 with inorganic nanoparticles has produced a number of nanozymes
      showing peroxidase or catalase activities. CeO2 nanoparticle (nanoceria) is a
      classical nanozyme. Herein, a fluorescently labeled DNA is used as a probe, and
      H2O2 can readily displace adsorbed DNA from nanoceria, resulting in over 20-fold
      fluorescence enhancement. The displacement mechanism instead of oxidative DNA
      cleavage is confirmed by denaturing gel electrophoresis and surface group pKa
      measurement. This system can sensitively detect H2O2 down to 130 nM (4.4 parts
      per-billion). When coupled with glucose oxidase, glucose is detected down to 8.9
      MUM in buffer. Detection in serum is also achieved with results comparable with
      that from a commercial glucose meter. With an understanding of the ligand role of
      H2O2, new applications in rational materials design, sensor development, and drug
      delivery can be further exploited. 

PMID- 25574929
TI  - The enduring importance of animal models in understanding periodontal disease.
AB  - Whereas no single animal model can reproduce the complexity of periodontitis,
      different aspects of the disease can be addressed by distinct models. Despite
      their limitations, animal models are essential for testing the biological
      significance of in vitro findings and for establishing cause-and-effect
      relationships relevant to clinical observations, which are typically correlative.
      We provide evidence that animal-based studies have generated a durable framework
      for dissecting the mechanistic basis of periodontitis. These studies have
      solidified the etiologic role of bacteria in initiating the inflammatory response
      that leads to periodontal bone loss and have identified key mediators (IL-1, TNF,
      prostaglandins, complement, RANKL) that induce inflammatory breakdown. Moreover,
      animal studies suggest that dysbiosis, rather than individual bacterial species,
      are important in initiating periodontal bone loss and have introduced the concept
      that organisms previously considered commensals can play important roles as
      accessory pathogens or pathobionts. These studies have also provided insight as
      to how systemic conditions, such as diabetes or leukocyte adhesion deficiency,
      contribute to tissue destruction. In addition, animal studies have identified and
      been useful in testing therapeutic targets. 

PMID- 25574934
TI  - Production of medical isotopes from a thorium target irradiated by light charged
      particles up to 70 MeV.
AB  - The irradiation of a thorium target by light charged particles (protons and
      deuterons) leads to the production of several isotopes of medical interest.
      Direct nuclear reaction allows the production of Protactinium-230 which decays to
      Uranium-230 the mother nucleus of Thorium-226, a promising isotope for alpha
      radionuclide therapy. The fission of Thorium-232 produces fragments of interest
      like Molybdenum-99, Iodine-131 and Cadmium-115g. We focus our study on the
      production of these isotopes, performing new cross section measurements and
      calculating production yields. Our new sets of data are compared with the
      literature and the last version of the TALYS code. 

PMID- 25574933
TI  - The bank of biological samples representing individuals exposed to long-term
      ionizing radiation at various doses.
AB  - Collection and storage of biological specimens in biobanks aims to obtain and
      preserve samples of different kinds for biological and medical studies. Here we
      present a description of the Bank of Biological Materials (BBM) housed by the
      Seversk Biophysical Research Centre (SBRC; Seversk, Russia). The main goal of
      maintaining the BBM is to collect and store biological samples suitable for
      genetic studies of people exposed to long-term ionizing radiation. Currently, the
      collection includes 19,194 biological specimens obtained from 8105 donors, of
      whom 42.3% are diagnosed with malignant neoplasms, 28.7% are healthy residents of
      the city of Seversk, 18.8% are healthy employees of the Siberian Group of
      Chemical Enterprises (SGCE), and 10.2% are patients diagnosed with acute
      myocardial infarction. The donors were enrolled using the Regional Medical and
      Dosimetric Register database created by the SBRC. For each donor, DNA specimens
      were extracted from peripheral blood and tissues and cell suspensions for
      cytogenetic analysis were prepared routinely. The BBM's unique collection is
      suitable primarily for studies of individual radiosensitivity of humans (IRH),
      and genetic aspects of the pathophysiology of common human diseases, especially
      in populations exposed to long-term low-dose ionizing radiation. 

PMID- 25574936
TI  - PFO-DBT:MEH-PPV:PC71BM ternary blend assisted platform as a photodetector.
AB  - We present a ternary blend-based bulk heterojunction ITO/PEDOT:PSS/PFO-DBT: MEH
      PPV:PC71BM/LiF/Al photodetector. Enhanced optical absorption range of the active
      film has been achieved by blending two donor components viz. poly[2,7-(9,9-di
      octyl-fluorene)-alt-4,7-bis(thiophen-2-yl)benzo-2,1,3-thiadiazole] (PFO-DBT) and
      poly(2-methoxy-5(2'-ethylhexyloxy) phenylenevinylene (MEH-PPV) along with an
      acceptor component, i.e., (6,6)-phenyl-C71 hexnoic acid methyl ester. The
      dependency of the generation rate of free charge carriers in the organic
      photodetector (OPD) on varied incident optical power density was investigated as
      a function of different reverse biasing voltages. The photocurrent showed
      significant enhancement as the intensity of light impinging on active area of OPD
      is increased. The ratio of Ilight to Idark of fabricated device at -3 V was ~3.5
      * 10(4). The dynamic behaviour of the OPD under on/off switching irradiation
      revealed that sensor exhibits quick response and recovery time of ~800 ms and 500
      ms, respectively. Besides reliability and repeatability in the photoresponse
      characteristics, the cost-effective and eco-friendly fabrication is the added
      benefit of the fabricated OPD.

PMID- 25574935
TI  - Class Energy Image analysis for video sensor-based gait recognition: a review.
AB  - Gait is a unique perceptible biometric feature at larger distances, and the gait
      representation approach plays a key role in a video sensor-based gait recognition
      system. Class Energy Image is one of the most important gait representation
      methods based on appearance, which has received lots of attentions. In this
      paper, we reviewed the expressions and meanings of various Class Energy Image
      approaches, and analyzed the information in the Class Energy Images. Furthermore,
      the effectiveness and robustness of these approaches were compared on the
      benchmark gait databases. We outlined the research challenges and provided
      promising future directions for the field. To the best of our knowledge, this is
      the first review that focuses on Class Energy Image. It can provide a useful
      reference in the literature of video sensor-based gait representation approach. 

PMID- 25574938
TI  - Neural attention and evaluative responses to gay and lesbian couples.
AB  - The goal of the current study was to examine whether differential neural
      attentional capture and evaluative responses for out-group homosexual relative to
      in-group heterosexual targets occur during social categorization. To this end, 36
      heterosexual participants were presented with pictures of heterosexual and
      homosexual couples in a picture-viewing task that was designed to assess implicit
      levels of discomfort toward homosexuality and explicit evaluations of
      pleasantness toward the images. Neural activity in the form of
      electroencephalogram was recorded during the presentation of the pictures, and
      event-related potentials resulting from these stimuli were examined. Participants
      also completed questionnaires that assessed the degree to which they socialized
      with gays and lesbians. Results demonstrated that relative to straight couples,
      larger P2 amplitude was observed in response to gay but not to lesbian couples.
      However, both gay and lesbian couples yielded a larger late positive potential
      than straight couples. Moreover, the degree to which participants differentially
      directed early neural attention to out-group lesbian versus in-group straight
      couples was related to their familiarity with homosexual individuals. This work,
      which provides an initial understanding of the neural underpinnings of attention
      toward homosexual couples, suggests that differences in the processing of sexual
      orientation can occur as early as 200 ms and may be moderated by familiarity.

PMID- 25574937
TI  - An integrated backscatter ultrasound technique for the detection of coronary and
      carotid atherosclerotic lesions.
AB  - The instability of carotid and coronary plaques has been reported to be
      associated with acute coronary syndrome, strokes and other cerebrovascular
      events. Therefore, recognition of the tissue characteristics of carotid and
      coronary plaques is important to understand and prevent coronary and cerebral
      artery disease. Recently, an ultrasound integrated backscatter (IB) technique has
      been developed. The ultrasound IB power ratio is a function of the difference in
      acoustic characteristic impedance between the medium and target tissue, and the
      acoustic characteristic impedance is determined by the density of tissue
      multiplied by the speed of sound. This concept allows for tissue characterization
      of carotid and coronary plaques for risk stratification of patients with coronary
      and cerebral artery disease. Two- and three-dimensional IB color-coded maps for
      the evaluation of tissue components consist of four major components: fibrous,
      dense fibrosis, lipid pool and calcification. Although several ultrasound
      techniques using special mathematical algorithms have been reported, a growing
      body of literature has shown the reliability and usefulness of the IB technique
      for the tissue characterization of carotid and coronary plaques. This review
      summarizes concepts, experimental procedures, image reliability and the
      application of the IB technique. Furthermore, the IB technique is compared with
      other techniques. 

PMID- 25574940
TI  - Diagnosis of drowning using post-mortem computed tomography - state of the art.
AB  - AIM OF THE STUDY: Recent studies using post-mortem computed tomography (PMCT)
      have suggested this imaging modality is of value in the positive diagnosis of
      drowning. We summarize the data from the literature regarding the diagnostic
      value of CT in cases of drowning. MATERIAL AND METHODS: We performed an all
      language search of literature published from 1999 to 2013 with the key words
      "post-mortem CT scan", "drowning and CT scan", "near-drowning diagnosis", and
      "drowning diagnosis". RESULTS: Only 11 articles, whose data enabled complementary
      statistical analysis, were included. The presence of fluid and sediment in
      paranasal sinuses appear to be the determinants of the diagnosis of drowning. The
      presence of fluid in the sinuses had a sensitivity of 100%, and of 90% in the
      trachea and main bronchi. The results were completed by the high specificity of
      the presence of sediment in the paranasal sinuses, upper airways and stomach,
      which was 100% for all three. Haemodilution was present in cases of drowning (p <
      0.001). The values made it possible to formulate a decision algorithm for the
      diagnosis of drowning.

PMID- 25574939
TI  - The effect of social support features and gamification on a Web-based
      intervention for rheumatoid arthritis patients: randomized controlled trial.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is chronic systematic disease that affects
      people during the most productive period of their lives. Web-based health
      interventions have been effective in many studies; however, there is little
      evidence and few studies showing the effectiveness of online social support and
      especially gamification on patients' behavioral and health outcomes. OBJECTIVE:
      The aim of this study was to look into the effects of a Web-based intervention
      that included online social support features and gamification on physical
      activity, health care utilization, medication overuse, empowerment, and RA
      knowledge of RA patients. The effect of gamification on website use was also
      investigated. METHODS: We conducted a 5-arm parallel randomized controlled trial
      for RA patients in Ticino (Italian-speaking part of Switzerland). A total of 157
      patients were recruited through brochures left with physicians and were randomly
      allocated to 1 of 4 experimental conditions with different types of access to
      online social support and gamification features and a control group that had no
      access to the website. Data were collected at 3 time points through
      questionnaires at baseline, posttest 2 months later, and at follow-up after
      another 2 months. Primary outcomes were physical activity, health care
      utilization, and medication overuse; secondary outcomes included empowerment and
      RA knowledge. All outcomes were self-reported. Intention-to-treat analysis was
      followed and multilevel linear mixed models were used to study the change of
      outcomes over time. RESULTS: The best-fit multilevel models (growth curve models)
      that described the change in the primary outcomes over the course of the
      intervention included time and empowerment as time-variant predictors. The growth
      curve analyses of experimental conditions were compared to the control group.
      Physical activity increased over time for patients having access to social
      support sections plus gaming (unstandardized beta coefficient [B]=3.39, P=.02).
      Health care utilization showed a significant decrease for patients accessing
      social support features (B=-0.41, P=.01) and patients accessing both social
      support features and gaming (B=-0.33, P=.03). Patients who had access to either
      social support sections or the gaming experience of the website gained more
      empowerment (B=2.59, P=.03; B=2.29, P=.05; respectively). Patients who were
      offered a gamified experience used the website more often than the ones without
      gaming (t91=-2.41, P=.02; U=812, P=.02). CONCLUSIONS: The Web-based intervention
      had a positive impact (more desirable outcomes) on intervention groups compared
      to the control group. Social support sections on the website decreased health
      care utilization and medication overuse and increased empowerment. Gamification
      alone or with social support increased physical activity and empowerment and
      decreased health care utilization. This study provides evidence demonstrating the
      potential positive effect of gamification and online social support on health and
      behavioral outcomes. TRIAL REGISTRATION: International Standard Randomized
      Controlled Trial Number (ISRCTN): 57366516; http://www.controlled-trials.
      com/ISRCTN57366516 (Archived by webcite at http://www.webcitation.org/6PBvvAvvV).

PMID- 25574942
TI  - Possibilities of post-mortem diagnostics, including immunodiagnostics, in cases
      of sudden death due to anaphylactic and anaphylactoid reactions.
AB  - Postmortem diagnostics of anaphylactic and anaphylactoid reaction as the cause of
      death in cases of sudden deaths without witnesses, as well as those in which
      circumstances of sudden disease and then death are known, seems to be very
      difficult. This is caused by the lack of characteristic macro- or microscopic
      changes to internal organs resulting from a short, or even very short time, that
      elapses from the action of the etiological factor till death. In the above
      mentioned cases it is often impossible to establish univocally the cause of
      death, despite considering information on the cause of disease and its clinical
      symptoms. On the basis of 2 cases of sudden deaths resulted from the intake of
      hazel nuts, and the administration of contrast agent before radiological
      examination, the authors discuss the usefulness of postmortem determinations of
      tryptase and IgE in blood for diagnostics of deaths resulting from anaphylactic
      and anaphylactoid reaction, respectively. 

PMID- 25574941
TI  - Medico-legal aspect of amphetamine-related deaths.
AB  - The subject of the work included 41 cases of death in which amphetamine was
      involved as the direct or indirect cause. Identification and determination of
      xenobiotics in blood samples collected from post-mortem cases were performed by
      high-performance liquid chromatography coupled with tandem mass spectrometry with
      electrospray ionisation (HPLC-ESI-MS-MS). Only for two cases was the cause of
      death amphetamine poisoning. In most of the investigated cases the death was
      caused by poisoning due to complex amphetamine and other psychoactive substances
      (e.g. opiates, benzodiazepines, cocaine). In other cases, multi-organ damage
      (fall from a height, traffic accident), a puncture wound and wound incised,
      drowning, or asphyxiation by hanging were reported. It can be explained as risky,
      murderous, or suicidal actions of people who were under the influence of
      amphetamines. The presented paper focuses on the interpretation of amphetamine
      concentration in blood samples from the perspective of direct or indirect cause
      of death. 

PMID- 25574943
TI  - Medico-legal analysis of a case of mass shooting.
AB  - Despite the existence of organised crime in Slovakia, no case has ever been
      monitored in which one individual used a firearm against several people, as
      happens in the U.S. or in Western Europe. The aim of this work is to demonstrate
      a "unique" case in the history of Slovak criminality, when six members of one
      family were killed and some other accidental victims were wounded or even killed
      by one perpetrator using a firearm. 

PMID- 25574944
TI  - The necessity of repeated assessment of imaging studies contained in medical
      records in medico-legal opinions.
AB  - The paper presents two case reports of living victims, in which imaging studies
      of the chest conducted at a medical facility were an essential part of the medico
      legal opinion. The first case was that of a young male hospitalized due to CT
      evidence of bilateral rib fractions, who claimed to have been assaulted by police
      officers. The other case was that of a six week old baby hospitalized due to
      chest X-ray evidence of right hand side rib fractions. The chest X-ray was
      performed due to one bruise found on the baby's forehead and two small bruises on
      the back, which gave rise to suspicions of child abuse. In both cases, expert
      witnesses in radiology definitively excluded the presence of any fractures. These
      cases indicate that a new assessment of imaging studies contained in medical
      records is needed. Expert opinions based solely on the description of imaging
      studies may result in grave consequences. 

PMID- 25574945
TI  - The motivation behind extended suicide.
AB  - The investigation of motivation of suicidal behaviour in cases of so-called
      extended suicide is of great importance from a forensic-psychological viewpoint.
      The initiator of such action is often a person suffering from endogenous
      depression. The motives behind successful suicide are generally not known. This
      paper aims to demonstrate the motives behind the successful suicide, less
      frequent in our conditions, of two family members - a father and a son. The case
      has been thoroughly analysed by morphological methods with the help of additional
      laboratory tests. At the centre was a suicide letter which was hidden in a very
      unusual way and which was elucidated only thanks to autopsy of both persons. The
      manner of realisation - hanging - was among the most frequent in the region and
      in the state too. The men were not under the influence of any toxic substances.
      The motivation behind the suicide was an escape from hard living conditions. 

PMID- 25574946
TI  - PLEKHM1: a multiprotein adaptor for the endolysosomal system.
AB  - Two papers by McEwan et al. (McEwan et al., 2015a, 2015b) identify interactions
      of PLEKHM1 with autophagosome-associated Atg8 proteins and Salmonella typhimurium
      effector, SifA, linking autophagy and the Salmonella-containing vacuole (SCV) to
      the endolysosomal Rab7/HOPS-regulated tethering machinery.

PMID- 25574947
TI  - SLX4: not SIMply a nuclease scaffold?
AB  - In this issue, Guervilly et al. (2015) and Ouyang et al. (2015) identify SUMO
      interacting motifs (SIMs) in the SLX4 DNA repair nuclease scaffold protein that
      promote its functions in genome stability maintenance pathways independently of
      its ubiquitin-binding properties.

PMID- 25574949
TI  - Hydroxyamination of olefins using Br-N-(CO2Me)2.
AB  - The hydroxyamination reagent Br-N-(CO2Me)2 underwent Markovnikov addition to
      various olefins in the presence of catalytic BF3.OEt2 and provides efficient
      access to aminoalcohols. The reaction provided the trans-1-bromo, 2-N-bis
      carbamate adduct stereoisomer in all cases. The resulting adduct underwent
      cyclization to give an oxazolidinone, which could be readily hydrolyzed to an
      oxazolidin-2-one or an amino alcohol. 

PMID- 25574951
TI  - Dynamics of droplet impact on hydrophobic/icephobic concrete with the potential
      for superhydrophobicity.
AB  - The ability of superhydrophobic surfaces to resist wetting and repel impinging
      water droplets is not less important for practical applications than the contact
      angle and contact angle hysteresis. Here we study novel hydrophobic concrete
      (with the potential for superhydrophobicity) and its ability to repel incoming
      droplets (e.g., rain). It is found that the onset of the pinning mode can be
      delayed by changing the surface topography. Also, the pinning or breakup of
      droplets of higher velocities depends on the incoming angle. Hydrophobic concrete
      with better pinning resistance showed less tendency for ice accretion. 

PMID- 25574948
TI  - The Streptococcus mutans irvA gene encodes a trans-acting riboregulatory mRNA.
AB  - In both prokaryotes and eukaryotes, insight into gene function is typically
      obtained by in silico homology searches and/or phenotypic analyses of strains
      bearing mutations within open reading frames. However, the studies herein
      illustrate how mRNA function is not limited to the expression of a cognate
      protein. We demonstrate that a stress-induced protein-encoding mRNA (irvA) from
      the dental caries pathogen Streptococcus mutans directly modulates target mRNA
      (gbpC) stability through seed pairing interactions. The 5' untranslated region of
      irvA mRNA is a trans riboregulator of gbpC and a critical activator of the DDAG
      stress response, whereas IrvA functions independently in the regulation of
      natural competence. The irvA riboregulatory domain controls GbpC production by
      forming irvA-gbpC hybrid mRNA duplexes that prevent gbpC degradation by an RNase
      J2-mediated pathway. These studies implicate a potentially ubiquitous role for
      typical protein-encoding mRNAs as riboregulators, which could alter current
      concepts in gene regulation.

PMID- 25574950
TI  - Atmospheric processing outside clouds increases soluble iron in mineral dust.
AB  - Iron (Fe) is a key micronutrient regulating primary productivity in many parts of
      the global ocean. Dust deposition is an important source of Fe to the surface
      ocean, but most of this Fe is biologically unavailable. Atmospheric processing
      and reworking of Fe in dust aerosol can increase the bioavailable Fe inputs to
      the ocean, yet the processes are not well understood. Here, we experimentally
      simulate and model the cycling of Fe-bearing dust between wet aerosol and cloud
      droplets. Our results show that insoluble Fe in dust particles readily dissolves
      under acidic conditions relevant to wet aerosols. By contrast, under the higher
      pH conditions generally relevant to clouds, Fe dissolution tends to stop, and
      dissolved Fe precipitates as poorly crystalline nanoparticles. If the dust
      bearing cloud droplets evaporated again (returning to the wet aerosol stage with
      low pH), those neo-formed Fe nanoparticles quickly redissolve, while the
      refractory Fe-bearing phases continue to dissolve gradually. Overall, the
      duration of the acidic, wet aerosol stage ultimately increases the amount of
      potentially bioavailable Fe delivered to oceans, while conditions in clouds favor
      the formation of Fe-rich nanoparticles in the atmosphere. 

PMID- 25574952
TI  - Reversible Janus particle assembly via responsive host-guest interactions.
AB  - Reversible assembly of Janus particles was manipulated by host-guest interaction
      of beta-cyclodextrin (beta-CD) and azobenzene. One side of every Janus particle
      was modified with beta-CD. Superstructures of Janus particles were formed by
      adding azobenzene-containing polymers to the dispersion of Janus particles. The
      superstructures were reversibly disassembled by adding alpha-CD or light
      irradiation. 

PMID- 25574953
TI  - The influence of amino acid sequence on structure and morphology of
      polydiacetylene containing peptide fibres.
AB  - A systematic study was performed on the influence of charge and steric hindrance
      on the assembly into fibres of a series of pentameric peptides based on the well
      known beta-sheet forming sequence Gly-Ala-Gly-Ala-Gly, which were N-terminally
      acylated with pentacosadiynoic acid. To investigate the effect of steric
      hindrance and charge repulsion on the fibre structure, either the N-terminal or
      the C-terminal amino acid in the sequence was replaced by a glutamic acid or
      lysine residue. Furthermore, peptide amphiphiles (PAs) with an amide or a free
      acid group at the C-terminus were compared. Steric hindrance and charge repulsion
      were addressed individually by varying the pH during and after fibre preparation.
      The self-assembled structures were examined with circular dichroism (CD)
      spectroscopy and transmission electron microscopy (TEM). UV spectroscopy was used
      to probe the diacetylene packing in the hydrophobic tail, both by polymerisation
      behaviour and chromatic properties of the polymers. In brief, the assembly was
      hindered more if the modification was close to the alkyl tail, and glutamic acid
      brought about a larger effect than lysine. PAs with two charges yielded
      assemblies which after polymerisation were found to be the most susceptible
      towards changes in pH, behaving as a colour-based pH sensor. Typically, TEM and
      UV showed the same trends, indicating that a distorted morphology as observed
      with TEM is indicative of a poorer molecular packing of the peptide amphiphile
      fibres, probed via the changes in absorption of the polydiacetylene backbone. 

PMID- 25574954
TI  - A polydopamine layer as the nucleation center of MOF deposition on "inert"
      polymer surfaces to fabricate hierarchically structured porous films.
AB  - Effective deposition of MOFs on "inert" solid surfaces is very challenging. In
      this work, we found that polydopamine, which can be facilely and tightly formed
      on any types as well as any forms of solid surfaces, could be used as an
      effective nucleation center for MOF deposition. Based on this finding, various
      MOFs were successfully deposited onto nanofibrous polymer membranes, especially
      the commercially available "inert" ones, affording hierarchically structured
      porous films. 

PMID- 25574957
TI  - Lower prevalence of drug resistance mutations at first-line virological failure
      to first-line therapy with atripla vs. tenofovir + emtricitabine/lamivudine +
      efavirenz administered on a multiple tablet therapy.
AB  - BACKGROUND: Fixed-dose combination antiretroviral therapy administered as a
      single-tablet regimen (STR) may improve virologic suppression rates. The effect
      of STRs on development of resistance when virologic failure occurs on STRs is not
      known. OBJECTIVES: To compare the rate of emergent drug resistance mutations
      (DRMs) on first-line therapy with coformulated tenofovir disoproxil fumarate
      (TDF)/emtricitabine (FTC)/efavirenz (EFV) as an STR versus TDF, lamivudine (3TC)
      or FTC, and EFV given as non-STR. METHODS: Patients from eight cohorts and four
      randomized clinical trials who received first-line antiretroviral therapy with
      Atripla (STR group) or with TDF + FTC/3TC + EFV (non-STR group) were eligible if
      a genotypic resistance test was available immediately after the first episode of
      viral failure. The DRM list from the 2013 version of IAS-USA was used. RESULTS:
      One hundred and eighty-six patients were included in the final analysis, 122
      (65.6%) from eight cohorts and 64 (34.1%) from four randomized clinical trials.
      The overall proportion of patients with at least one DRM at viral failure was
      67.7%, including 53.4% (31 of 58) in the STR group vs. 74.2% (95 of 128) in the
      non-STR group (P = 0.005). Among patients exclusively from cohorts, at least one
      DRM was detected in 53.4% (31 of 58) in the STR group vs. 78.1% (50 of 64) in the
      non-STR group (P = 0.004). DRMs for individual drugs were: TDF, 15.5 vs. 16.4% (P
      = 0.87); 3TC/FTC, 31 vs. 35.2% (P = 0.58); and NNRTI, 51.7 vs. 65.6% (P = 0.07).
      The proportion of patients with an M184V/I among the 128 patients who received
      FTC was 32.8 vs. 36.2% among the 58 treated with 3TC (P = 0.65). CONCLUSIONS:
      Compared to patients receiving the STR-Atripla, those receiving the same
      components individually in a non-STR regimen have a statistically significantly
      increased risk of selecting for DRMs associated with their drugs on failure.

PMID- 25574955
TI  - Evidence for cryptic speciation in directly transmitted gyrodactylid parasites of
      Trinidadian guppies.
AB  - Cryptic species complexes are common among parasites, which tend to have large
      populations and are subject to rapid evolution. Such complexes may arise through
      host-parasite co-evolution and/or host switching. For parasites that reproduce
      directly on their host, there might be increased opportunities for sympatric
      speciation, either by exploiting different hosts or different micro-habitats
      within the same host. The genus Gyrodactylus is a specious group of viviparous
      monogeneans. These ectoparasites transfer between teleosts during social contact
      and cause significant host mortality. Their impact on the guppy (Poecilia
      reticulata), an iconic evolutionary and ecological model species, is well
      established and yet the population genetics and phylogenetics of these parasites
      remains understudied. Using mtDNA sequencing of the host and its parasites, we
      provide evidence of cryptic speciation in Gyrodactylus bullatarudis, G. poeciliae
      and G. turnbulli. For the COII gene, genetic divergence of lineages within each
      parasite species ranged between 5.7 and 17.2%, which is typical of the divergence
      observed between described species in this genus. Different lineages of G.
      turnbulli and G. poeciliae appear geographically isolated, which could imply
      allopatric speciation. In addition, for G. poeciliae, co-evolution with a
      different host species cannot be discarded due to its host range. This parasite
      was originally described on P. caucana, but for the first time here it is also
      recorded on the guppy. The two cryptic lineages of G. bullatarudis showed
      considerable geographic overlap. G. bullatarudis has a known wide host range and
      it can also utilize a killifish (Anablepsoides hartii) as a temporary host. This
      killifish is capable of migrating overland and it could act as a transmission
      vector between otherwise isolated populations. Additional genetic markers are
      needed to confirm the presence of these cryptic Gyrodactylus species complexes,
      potentially leading to more in-depth genetic, ecological and evolutionary
      analyses on this multi-host-parasite system. 

PMID- 25574956
TI  - Relationships of pulmonary function, inflammation, and T-cell activation and
      senescence in an HIV-infected cohort.
AB  - OBJECTIVE: To determine associations between circulating markers of immune
      activation, immune cell senescence, and inflammation with HIV-associated
      abnormalities of pulmonary function. DESIGN: HIV infection is an independent risk
      factor for abnormal pulmonary function. Immune activation, immune senescence, and
      chronic inflammation are characteristics of chronic HIV infection that have been
      associated with other HIV-associated comorbidities and may be related to
      pulmonary disease in this population. METHODS: Participants from an HIV-infected
      cohort (n = 147) completed pulmonary function testing (PFT). Markers of T-cell
      activation and senescence were determined by flow cytometry, and plasma levels of
      interleukin-6, interleukin-8, and C-reactive protein (CRP) were measured, as was
      telomere length of peripheral blood mononuclear cells (PBMC). Regression models
      adjusting for clinical risk factors were constructed to examine relationships
      between biomarkers and PFT outcomes. RESULTS: Activated CD25(+) T cells and
      activated/senescent CD69(+)/CD57(+)/CD28(null) CD4(+) T cells, interleukin-6, and
      CRP were associated with PFT abnormalities. Shortening of PBMC telomere length
      correlated with airflow obstruction and diffusing impairment. Paradoxically,
      circulating senescent CD57(+)/CD28(null) CD8(+) T cells were associated with
      better PFT outcomes. CONCLUSION: Circulating T cells expressing markers of
      activation and inflammatory cytokine levels are independently correlated with PFT
      abnormalities in HIV-infected persons. Overall telomere shortening was also
      associated with pulmonary dysfunction. The paradoxical association of senescent
      CD8(+) T cells and better PFT outcomes could suggest an unrecognized beneficial
      compensatory function of such cells or a redistribution of these cells from the
      circulation to local compartments. Further studies are needed to differentiate
      and characterize functional subsets of local pulmonary and circulating T-cell
      populations in HIV-associated pulmonary dysfunction.

PMID- 25574958
TI  - Antiretroviral drugs for prevention of mother-to-child transmission:
      pharmacologic considerations for a public health approach.
AB  - OBJECTIVE: Efavirenz-based antiretroviral therapy is recommended for prevention
      of mother-to-child transmission of HIV with two programmatic options: lifelong
      therapy for all women or treatment until cessation of breastfeeding. However, the
      risk of HIV resistance emerging after discontinuing efavirenz-based
      antiretroviral therapy is unclear. We review present knowledge surrounding the
      emergence of resistance after stopping efavirenz-based antiretroviral regimens.
      DESIGN: An expert review. METHODS: A literature review was conducted to identify
      studies assessing risk for emergence of efavirenz-related resistance following
      discontinuation of efavirenz-based antiretroviral regimens containing either
      lamivudine and zidovudine or tenofovir disoproxil fumarate and lamivudine.
      Discontinuation strategies including the use of 'pharmacologic tails' are
      discussed in the light of what is known about the pharmacology of the drugs.
      RESULTS: We found no head-to-head comparisons between zidovudine, lamivudine and
      efavirenz and tenofovir disoproxil fumarate, lamivudine and efavirenz. The risk
      for HIV resistance exists, even with a 5-7 day tail of zidovudine and lamivudine.
      For tenofovir disoproxil fumarate, lamivudine and efavirenz, we found no clinical
      data to inform a recommendation for a tail. CONCLUSION: In order to prevent
      emergence of resistance, a tail of at least 2 weeks in duration may be required
      when discontinuing efavirenz in a regimen containing zidovudine and lamivudine.
      Studies are needed to characterize the risk of resistance among women who
      discontinue tenofovir disoproxil fumarate, lamivudine and efavirenz.

PMID- 25574960
TI  - Prevalence, incidence and predictors of peripheral neuropathy in African adults
      with HIV infection within the DART trial.
AB  - OBJECTIVES: We investigated the prevalence, incidence and predictors of new
      peripheral neuropathy episodes in previously untreated, symptomatic HIV-infected
      Ugandan/Zimbabwean adults initiating zidovudine-based antiretroviral therapy
      (ART). DESIGN: An open-label, multicentre, randomized trial. METHODS: Peripheral
      neuropathy was self-reported at 12-weekly clinic visits. Cox regression models
      (excluding participants reporting preexisting peripheral neuropathy at ART
      initiation), considered sex; pre-ART WHO stage, age and CD4(+) cell count; CD4(+)
      cell count versus no CD4(+) cell count monitoring; and time-updated CD4(+) cell
      count, weight and use of stavudine, isoniazid and didanosine. RESULTS: Four
      hundred and twenty-one out of 3316(13%) patients reported preexisting peripheral
      neuropathy at ART initiation. Median (interquartile range, IQR) follow-up in 2895
      participants without preexisting peripheral neuropathy was 4.9 (4.7-5.4) years.
      Three hundred and fifty-four (12%) took stavudine as first-line substitution and
      518 (18%) took isoniazid during follow-up. Two hundred and ninety (11%)
      participants developed a new peripheral neuropathy episode, an incidence of 2.12
      per 100 person-years. Eighteen (0.1%) had a grade 3/4 episode. Independent
      predictors of peripheral neuropathy were current stavudine use [adjusted hazard
      ratio (a)HR 4.16 (95% confidence interval, 95% CI 3.06-5.66], current isoniazid
      use [aHR 1.59 (95% CI 1.02-2.47)] and current didanosine use [aHR 1.60 (95% CI
      1.19-2.14)]. Higher risks were independently associated with higher pre-ART
      weight [aHR (per+5 kg) 1.07 (95% CI 1.01-1.13)] and older age aHR (per 10 years
      older) 1.29 (95% CI 1.12-1.49), but there was no significant effect of sex (P =
      0.13), pre-ART CD4(+) cell count (P = 0.91) or CD4(+) cell count monitoring (P =
      0.73). CONCLUSION: Current stavudine, didanosine or isoniazid use continue to
      increase peripheral neuropathy risks, as does older age and weight at ART
      initiation; however, we found no evidence of increased risk in women in contrast
      to previous studies. The incidence of peripheral neuropathy may now be lower in
      ART programmes, as stavudine and didanosine are no longer recommended. All
      patients receiving isoniazid, either as part of antituberculosis (TB)
      chemotherapy or TB-preventive therapy, should receive pyridoxine as recommended
      in national guidelines.

PMID- 25574962
TI  - Selective acquisition of G190S in HIV-1 subtype A from Russia leading to
      efavirenz and nevirapine treatment failure.

PMID- 25574961
TI  - Complications of cesarean deliveries among HIV-infected women in the United
      States.
AB  - OBJECTIVE: To compare rates of complications associated with cesarean delivery in
      HIV-infected and HIV-uninfected women in the United States and to investigate
      trends in such complications across four study cycles spanning the implementation
      of HAART in the United States (1995-1996, 2000-2001, 2005-2006, 2010-2011).
      DESIGN: The Nationwide Inpatient Sample from the Healthcare Cost and Utilization
      Project is the largest all-payer hospital inpatient care database in the United
      States; when weighted to account for the complex sampling design, nationally
      representative estimates are derived. After restricting the study sample to women
      aged 15-49 years, our study sample consisted of approximately 1 090 000 cesarean
      delivery hospitalizations annually. METHODS: Complications associated with
      cesarean deliveries were categorized as infection, hemorrhage, or surgical
      trauma, based on groups of specific International Classification of Diseases 9th
      revision codes. Length of hospitalization, hospital charges, and in-hospital
      deaths were also examined. RESULTS: The rate of complications significantly
      decreased during the study periods for HIV-infected and HIV-uninfected women.
      However, rates of infectious complications and surgical trauma associated with
      cesarean deliveries remained higher among HIV-infected, compared with HIV
      uninfected women in 2010-2011, as did prolonged hospital stay and in-hospital
      deaths. Length of hospitalization decreased over time for cesarean deliveries of
      HIV-infected women to a greater extent compared with HIV-uninfected women.
      CONCLUSION: In the United States, rates of cesarean delivery complications
      decreased from 1995 to 2011. However, rates of infection, surgical trauma,
      hospital deaths, and prolonged hospitalization are still higher among HIV
      infected women. Clinicians should remain alert to this persistently increased
      risk of cesarean delivery complications among HIV-infected women.

PMID- 25574963
TI  - Antiretroviral nanoparticles: the future is now.

PMID- 25574959
TI  - Thrombocytopenia is associated with an increased risk of cancer during treated
      HIV disease.
AB  - OBJECTIVE: To assess the relationship between platelet counts and risk of AIDS
      and non-AIDS-defining events. DESIGN: Prospective cohort. METHODS: EuroSIDA
      patients with at least one platelet count were followed from baseline (first
      platelet >= 1 January 2005) until last visit or death. Multivariate Poisson
      regression was used to assess the relationship between current platelet counts
      and the incidence of non-AIDS-defining (pancreatitis, end-stage liver/renal
      disease, cancer, cardiovascular disease) and AIDS-defining events. RESULTS: There
      were 62 898 person-years of follow-up (PYFU) among 12 279 patients, including
      1168 non-AIDS-defining events [crude incidence 18.6/1000 PYFU, 95% confidence
      interval (CI) 17.5-19.6] and 735 AIDS-defining events (crude incidence 11.7/1000
      PYFU, 95% CI 10.8-12.5). Patients with thrombocytopenia (platelet count <=100 *
      10/l) had a slightly increased incidence of AIDS-defining events [adjusted
      incidence rate ratio (aIRR) 1.42, 95% CI 1.07-1.86], when compared to those with
      platelet counts 101-200 * 10/l, whereas the incidence of non-AIDS-defining events
      was more than two-fold higher (aIRR 2.66, 95% CI 2.17-3.26). Among non-AIDS
      defining events, the adjusted incidence of cancer (aIRR 2.20, 95% CI 1.61-3.01),
      but not cardiovascular disease (aIRR 0.66, 95% CI 0.32-1.34), was significantly
      higher in patients with thrombocytopenia. The association between
      thrombocytopenia and cancer remained unaltered in sensitivity analyses requiring
      repeated platelet counts to confirm thrombocytopenia and lagging platelets by 1
      year prior to clinical events. CONCLUSION: Patients with thrombocytopenia had
      increased incidence of AIDS-defining and non-AIDS-defining events, but the
      association with the latter, in particular cancer, was stronger. Future studies
      should investigate whether the pathophysiological processes underlying
      thrombocytopenia are associated with the development of cancer during treated HIV
      disease.

PMID- 25574965
TI  - Pulmonary complications associated with pegylated interferon and ribavirin in
      HIV/hepatitis C virus coinfected patients.

PMID- 25574964
TI  - Effects of atorvastatin and pravastatin on immune activation and T-cell function
      in antiretroviral therapy-suppressed HIV-1-infected patients.
AB  - This retrospective study was designed to assess statin effects on T-cell
      activation from HIV-infected individuals. Peripheral blood mononuclear cells from
      antiretroviral therapy suppressed HIV-infected individuals receiving atorvastatin
      or pravastatin were evaluated for T-cell activation, exhaustion and function.
      Atorvastatin was associated with a significant reduction in CD8 T-cell activation
      (HLA-DR, CD38/HLA-DR) and exhaustion (TIM-3, TIM-3/PD-1) whereas pravastatin had
      no effect. In contrast, pravastatin increased antigen specific interferon gamma
      production. These results suggest a differential effect of statins on immune
      activation and function. 

PMID- 25574966
TI  - Minor viral population with drug-resistant mutation and risk of persistent low
      level viremia or 'blips' in HIV-1 subtype C.

PMID- 25574969
TI  - Evaluation of electrostatic binding of PAMAM dendrimers and charged
      phthalocyanines by fluorescence correlation spectroscopy.
AB  - We have assessed host-guest interactions between PAMAM dendrimers and charged
      phthalocyanine probes by Fluorescence Correlation Spectroscopy (FCS). Our results
      show strong binding in water at low ionic strength with an affinity that
      decreases from KB ~ 10(9) to 10(8) M(-1) upon decreasing the phthalocyanine
      charge of z = -4, -2 and -1. The binding affinity also decreases significantly
      upon salt addition leading to KB values of ca. 10(5)-10(6) M(-1). The changes of
      binding affinity probed by varying the phthalocyanine charge, and by changing the
      ionic strength or pH conditions, allowed us to evaluate the electrostatic
      contribution (Kel) in dendrimer-phthalocyanine interactions. In particular, this
      approach afforded values of electrostatic potential for PAMAM dendrimers in water
      at low ionic strength and at dendrimer concentrations in the nanomolar range. The
      electrostatic potential of PAMAM generations 4 and 7 are around 50 mV in close
      agreement with theoretical estimates using the Poisson-Boltzmann cell model.
      Interestingly, the nonelectrostatic binding is significant and contributes even
      more than electrostatic binding to dendrimer-phthalocyanine interactions. The
      nonelectrostatic binding contributes to an affinity of KB above 10(5) M(-1), as
      measured under conditions of low dendrimer charge and high ionic strength, which
      makes these dendrimers promising hosts as drug carriers. 

PMID- 25574967
TI  - A case of iatrogenic adrenal suppression after co-administration of cobicistat
      and fluticasone nasal drops.

PMID- 25574968
TI  - Correlation of the apparent diffusion coefficient (ADC) with the standardized
      uptake value (SUV) in lymph node metastases of non-small cell lung cancer (NSCLC)
      patients using hybrid 18F-FDG PET/MRI.
AB  - OBJECTIVE: To compare the apparent diffusion coefficient (ADC) in lymph node
      metastases of non-small cell lung cancer (NSCLC) patients with standardized
      uptake values (SUV) derived from combined 18F-fluoro-deoxy-glucose-positron
      emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). MATERIAL AND
      METHODS: 38 patients with histopathologically proven NSCLC (mean age 60.1 +/- 9.5
      y) received whole-body PET/CT (Siemens mCTTM) 60 min after injection of a mean
      dose of 280 +/- 50 MBq 18F-FDG and subsequent PET/MRI (mean time after tracer
      injection: 139 +/- 26 min, Siemens Biograph mMR). During PET acquisition,
      simultaneous diffusion-weighted imaging (DWI, b values: 0, 500, 1000 s/mm2) was
      performed. A maximum of 10 lymph nodes per patient suspicious for malignancy were
      analyzed. Regions of interest (ROI) were drawn covering the entire lymph node on
      the attenuation-corrected PET-image and the monoexponential ADC-map. According to
      histopathology or radiological follow-up, lymph nodes were classified as benign
      or malignant. Pearson's correlation coefficients were calculated for all lymph
      node metastases correlating SUVmax and SUVmean with ADCmean. RESULTS: A total of
      146 suspicious lymph nodes were found in 25 patients. One hundred lymph nodes
      were eligible for final analysis. Ninety-one lymph nodes were classified as
      malignant and 9 as benign according to the reference standard. In malignant
      lesions, mean SUVmax was 9.1 +/- 3.8 and mean SUVmean was 6.0 +/- 2.5 while mean
      ADCmean was 877.0 +/- 128.6 x10(-5) mm2/s in PET/MRI. For all malignant lymph
      nodes, a weak, inverse correlation between SUVmax and ADCmean as well as SUVmean
      and ADCmean (r = -0.30, p<0.05 and r = -0.36, p<0.05) existed. CONCLUSION: The
      present data show a weak inverse correlation between increased glucose-metabolism
      and cellularity in lymph node metastases of NSCLC patients. 18F-FDG-PET and DWI
      thus may offer complementary information for the evaluation of treatment response
      in lymph node metastases of NSCLC.

PMID- 25574970
TI  - Genetically encoded tools: bridging the gap between neuronal identity and
      function.
AB  - Genetically encoded tools are positioned to serve a unique and critical role in
      bridging the gap between the genetic identity of neurons and their functional
      properties. However, the use of these tools is limited by our current
      understanding of cell-type identity. As we make technological advances that focus
      on capturing functional aspects of neurons such as connectivity, activity, and
      metabolic states, our understanding of neuronal identity will deepen and may
      enable the use of genetically encoded tools for modulating disease-specific
      circuits for therapeutic purposes.

PMID- 25574971
TI  - Unraveling the edge structures of platinum(111)-supported ultrathin FeO islands:
      the influence of oxidation state.
AB  - We used high-resolution scanning tunneling microscopy to study the structure of
      ultrathin FeO islands grown on Pt(111). Our focus is particularly on the edges of
      the FeO islands that are important in heterogeneous catalysis, as they host the
      active sites on inversed catalysts. To imitate various reaction environments we
      studied pristine, oxidized, and reduced FeO islands. Oxidation of the FeO islands
      by O2 exposure led to the formation of two types of O adatom dislocations and to
      a restructuring of the FeO islands, creating long O-rich edges and few short Fe
      terminated edges. In contrast, reducing the FeO islands led to a dominance of Fe
      rich edges and the occurrence of few and short O-rich edges. In addition, for
      reducing conditions we observed the formation of O vacancy dislocations on the
      FeO islands. Through the identification of O adatom and O vacancy dislocations
      known from closed ultrathin FeO films and geometrical considerations we unraveled
      the atomic structure of the predominant FeO boundaries of pristine, oxidized, and
      reduced FeO islands. The results indicate an astonishing flexibility of the FeO
      islands on Pt(111), since the predominant edge termination and the island shape
      depend strongly on the preparation conditions. 

PMID- 25574972
TI  - In situ growth of MOFs on the surface of si nanoparticles for highly efficient
      lithium storage: Si@MOF nanocomposites as anode materials for lithium-ion
      batteries.
AB  - A simple yet powerful one-pot strategy is developed to prepare metal-organic
      framework-coated silicon nanoparticles via in situ mechanochemical synthesis.
      After simple pyrolysis, the thus-obtained composite shows exceptional
      electrochemical properties with a lithium storage capacity up to 1050 mA h g(-1),
      excellent cycle stability (>99% capacity retention after 500 cycles) and
      outstanding rate performance. These characteristics, combined with their high
      stability and ease of fabrication, make such Si@MOF nanocomposites ideal
      alternative candidates as high-energy anode materials in lithium-ion batteries. 

PMID- 25574973
TI  - Analysis and Antioxidant Activity of Extracts from Broccoli (Brassica oleracea
      L.) Sprouts.
AB  - Samples prepared from fresh broccoli (Brassica oleracea L.) sprouts by water
      distillation or freeze-drying were examined for antioxidant activity using three
      assays. All samples exhibited dose-dependent antioxidant activity. The
      antioxidant activity ranged from 74.48 +/- 0.46% (less volatile sample) to 93.2
      +/- 0.2% (dichloromethane extract sample) at the level of 500 MUg/mL. Both
      dichloromethane extract samples from a water distillate of broccoli sprouts and
      freeze-dried broccoli sprouts showed potent antioxidant activity, which was
      comparable to that of BHT. Among the 43 compounds positively identified by gas
      chromatography-mass spectrometry, 5-methylthiopentylnitrile (31.64 MUg/g) was
      found in the greatest concentration, followed by 4-methylthiobutylisothiocyanate
      (14.55 MUg/g), 4-methylthiobutylnitrile (10.63 MUg/g), 3
      methylthiopropylisothiocyanate (3.00 MUg/g), and 4-methylpentylisothiocyanate
      (2.48 MUg/g). These isothiocyanates are known to possess antioxidant properties.
      Possible phenolic antioxidants found are 4-(1-methylpropyl)phenol (0.012 MUg/g),
      4-methylphenol (0.159 MUg/g), and 2-methoxy-4-vinylphenol (0.009 MUg/g). The
      present study demonstrates that broccoli sprouts are a good source of natural
      antioxidants.

PMID- 25574974
TI  - The impact of TiO2 nanoparticles on uptake and toxicity of benzo(a)pyrene in the
      blue mussel (Mytilus edulis).
AB  - Nanoparticles are emerging contaminants of concern. Knowledge on their
      environmental impacts is scarce, especially on their interactive effects with
      other contaminants. In this study we investigated effects of titanium dioxide
      nanoparticles (TiO2NP) on the blue mussel (Mytilus edulis) and determined their
      influence on the bioavailability and toxicity of benzo(a)pyrene (B(a)P), a
      carcinogenic polyaromatic hydrocarbon (PAH). Blue mussels were exposed to either
      TiO2NP (0.2 and 2.0 mg L(-1)) or B(a)P (20 MUg L(-1)) and to the respective
      combinations of these two compounds. Aqueous contaminant concentrations, the
      uptake of Ti and B(a)P into mussel soft tissue, effects on oxidative stress and
      chromosomal damage were analyzed. The uncoated TiO2NP agglomerated rapidly in the
      seawater. The presence of TiO2NP significantly reduced the bioavailability of
      B(a)P, shown by lowered B(a)P concentrations in exposure tanks and in mussel
      tissue. The activities of antioxidant enzyme superoxide dismutase (SOD), catalase
      (CAT) and glutathione peroxidase (GPx) were impacted by the various exposure
      regimes, indicating oxidative stress in the contaminant exposure groups. While
      SOD activity was increased only in the 0.2TiO2NP exposure group, CAT activity was
      enhanced in both combined exposure groups. The GPx activity was increased only in
      the groups exposed to the two single compounds. In hemocytes, increased
      chromosomal damage was detected in mussels exposed to the single compounds, which
      was further increased after exposure to the combination of compounds. In this
      study we show that the presence of TiO2NP in the exposure system reduced B(a)P
      uptake in blue mussels. However, since most biomarker responses did not decrease
      despite of the lower B(a)P uptake in combined exposures, the results suggest that
      TiO2NP can act as additional stressor, or potentially alters B(a)P toxicity by
      activation.

PMID- 25574976
TI  - Knowledge of dental interns towards emergency management of avulsed tooth in
      dental colleges in Nepal.
AB  - BACKGROUND: Avulsion is most common traumatic injury of tooth. Adequate knowledge
      about management of this situation can save a tooth. This study was conducted to
      investigate the knowledge and attitude of dental interns of Nepal in the
      management of tooth avulsion and also evaluate the need for further education on
      managing avulsed teeth. METHODS: A cross-sectional survey consisting of 18 items
      were filled, collected and mailed back by 121 interns of Nepal from five dental
      colleges. The study period was from July to September 2013. All returned
      questionnaires were analyzed using SPSS 17.0. RESULTS: Dental interns with more
      efficient in answering questions regarding- ideal time for replantation of an
      avulsed tooth (p=0.024), splinting period (p=0.008), the critical factor in the
      outcome of replanted tooth (p=0.010) and the better prognosis with open apex
      (p=0.001). Prior knowledge about management of avulsed tooth had a role in
      correctly answering questions on type of splint used (p=0.022) and better
      prognosis with open apex (p=0.018). Attending educational program on trauma
      management helped them in correctly answering questions on avulsed permanent
      tooth to be replanted (p=0.043) and the type of splint used (p=0.014).
      CONCLUSIONS: Dental interns experience, prior knowledge and educational programs
      with dental management regarding traumatic injuries scored significantly higher
      than without such training or acquired information. However further knowledge
      needs to be enhanced by continued educational programs to ensure appropriate
      treatment.

PMID- 25574975
TI  - Impacts of climate change and land-use scenarios on Margaritifera margaritifera,
      an environmental indicator and endangered species.
AB  - In this study, we assess the impacts of future climate and land-use in the Beca
      River (northern Portugal) under different scenarios and how this will translate
      into the conservation status of the endangered pearl mussel Margaritifera
      margaritifera (Linnaeus, 1758). This species is currently present in several
      stretches of the Beca River that still hold adequate ecological conditions.
      However, the species is threatened by projected declines in precipitation for the
      21st century, with implication on the river flows and water depths that might
      decrease below the species requisites. This situation could be especially
      critical during summer conditions since the ecological flows may not be assured
      and several river stretches may be converted into stagnant isolated pools. The
      habitat connectivity will also be affected with reverberating effects on the
      mobility of Salmo trutta, the host of M. margaritifera, with consequences in the
      reproduction and recruitment of pearl mussels. In addition, human-related threats
      mostly associated with the presence of dams and an predicted increases in
      wildfires in the future. While the presence of dams may decrease even further the
      connectivity and river flow, with wildfires the major threat will be related to
      the wash out of burned areas during storms, eventually causing the disappearance
      of the mussels, especially the juveniles. In view of future climate and land-use
      change scenarios, conservation strategies are proposed, including the negotiation
      of ecological flows with the dam promoters, the replanting of riparian vegetation
      along the water course and the reintroduction of native tree species throughout
      the catchment. 

PMID- 25574977
TI  - General health status of women of reproductive age in Nepal.
AB  - BACKGROUND: Women of reproductive age in Nepal are vulnerable to different health
      problems, which can jeopardize physical and mental development of fetus and
      mother. The aim of this study was to explore the general health status of
      reproductive aged women of Nepal. METHODS: Household survey and health camps were
      conducted in selected Village Development Committees of nine districts in three
      ecological regions of Nepal in 2011-2012. Structured questionnaires were used to
      collect the required information from women of reproductive age (15 to 49 years)
      group. Measurement of blood pressure, anthropometry and presence of thyroid
      swelling, jaundice and edema of the participants were performed. RESULTS: In
      total, 21111 women were interviewed. Women having hypertension (9.4%, n=85) and
      jaundice (0.9%, n=8) were predominant in the Mountain. Prevalence of Grade 2
      thyroid (6.3%, n=320) was found higher in Terai. Prevalence of underweight women
      was significantly higher in women of Terai (26.6%, n=1235) (p<0.001). Prevalence
      of anemia was 26.0% (n=2165) in Hills and 24.7% (n=1232) in Terai. Among the
      pregnant women more than half were anemic and more underweight women were anemic
      (25.4%, n=619). Anemia was significantly associated with pregnancy (p<0.001),
      Hill and Terai ecological regions (p<0.001) and underweight women (p<0.001).
      CONCLUSIONS: General health status of women of reproductive age is still poor.
      Thus, such high-risk population should be the focus of the government and
      concerned bodies to improve the general health status of women and children.

PMID- 25574978
TI  - Return to preinjury status after routine knee arthroscopy in military population.
AB  - BACKGROUND: Knee arthroscopy is frequently advised procedure for knee-related
      problems in serving soldiers. The scanty published literatures have documented
      wide range of recovery duration ranging from nine days to four weeks even for
      routine uncomplicated arthroscopy. However, neither of these studies evaluated
      military population, where arthroscopic procedures are frequent and physical
      demands are different. The aim of this study was to ascertain the time required
      to return to unrestricted physical activities in serving military population.
      METHODS: This was a prospective descriptive study enrolling 51 patients who
      underwent two portal arthroscopic procedures like diagnostic arthroscopy,
      meniscectomy, loose body removal and excision of plica or combination of these. A
      uniform home based physiotherapy protocol was used for everyone. All of them were
      followed up at 2nd, 4th, 6th, 8th and 12th postoperative weeks. At each follow
      up, 2000 International Knee Documentation Committee subjective knee evaluation
      form was filled and submitted for analysis. RESULTS: Although all of our patients
      were able to walk around without any support at two weeks follow up, 88% had
      restriction to activities of daily living because of knee related problems. The
      mean International Knee Documentation Committee score was 41 at 1st follow up,
      which gradually improved to 64, 86, 94, 94 at 4th, 6th, 8th and 12th week follow
      up respectively. At 6 weeks 91% resumed their preinjury status which reached 94%
      in eight weeks. CONCLUSIONS: Most of the soldiers return to unrestricted
      activities within six to eight weeks after diagnostic arthroscopy, meniscectomy,
      loose body removal and excision of plica or combination of these procedures.

PMID- 25574979
TI  - Reproductive morbidity in a village of Kathmandu.
AB  - BACKGROUND: Reproductive morbidity has been a less studied area in developing
      countries. Prevalence of reproductive morbidity and health seeking behavior
      pertaining to it is little known. To reveal the magnitude, this study was carried
      out in a village of Kathmandu district. The objective of the study was to find
      out prevalence of reproductive morbidity and service utilized for them. METHODS:
      A random cross-sectional study was carried out among 200 women of reproductive
      age years in a village using household survey and structured questionnaire.
      RESULTS: The study revealed that 72 percent (144) women of reproductive age years
      have experienced reproductive problem. Gynecological problems contributed for 81
      (40%) women and obstetric problems for about 51% of the married women (48 out of
      94). Service seeking was found to be very low for gynecological morbidity.
      CONCLUSIONS: Reproductive morbidity was found to be very high in the community.
      The prevalence of obstetric morbidity was almost in half the study population,
      whereas gynaecological morbidity was about forty percent among the women of
      reproductive age group. However, seeking care for reproductive morbidity was low
      which requires more attention.

PMID- 25574980
TI  - Correlation between knowledge, attitude and practices on HIV and AIDS: cases from
      the Kathmandu Valley.
AB  - BACKGROUND: This study investigated the correlation between knowledge, attitude
      and practices on HIV and AIDS in the context of Nepal.The study was conducted
      among the 404 respondents; selected from the transport workers, garment factory
      workers, brick factory workers and health workers. METHODS: It was non
      experimental cross sectional study based on descriptive as well as correlational
      research design. Simple random technique was used to select the respondents.
      Survey was conducted to collect the primary data and r value was used to analyze
      the correlation between variables. RESULTS: Finding shows that 391 (96.8%)
      respondents have heard about HIV and AIDS; among them 388 (95.8%) respondents
      were mentioned that they had knowledge of way of HIV transmission also. Total 50
      out of 171 unmarried (29.2%) respondents had pre-marital sexual experience. It
      was found that only 71 (25.6%) respondents had used the condom during their first
      time sexual intercourse.There was significant association (p=.000) found between
      the knowledge on way of HIV transmission and occupation of respondents, similarly
      relationship found (r = .815, p = .000 (2-tailed) between marriage age and age of
      first time sexual intercourseof respondents. But there was no relationship (r =
      .097 and p =.106 (2-tailed) found between Knowledge on way of HIV transmission
      and sex with non-regular sex partners. CONCLUSIONS: Data showed that safer sex
      practices was low than the level of knowledge. The educational status of
      respondents shows the positive association with attitude towards the necessary to
      have knowledge of HIV and AIDS.

PMID- 25574981
TI  - Tracheostomy in tertiary care health institution.
AB  - BACKGROUND: Tracheostomy is the most obliging and one of the oldest operations in
      the history of surgery. It is channel between the trachea and skin in the midline
      in the neck. Most common indications are upper airway obstruction, mechanical
      respiratory insufficiency and pulmonary toileting etc. METHODS: It is a
      retrospective study done in a teaching hospital in eastern Nepal from 2005-2008.
      Medical records of 175 tracheostomized patients were reviewed. Demographic
      variations, indications and outcome were recorded and analyzed. RESULTS: Age
      ranged from 1 to 88 years. Most common age group was 21-30 years followed by 51
      60 years. Common indications for tracheostomy were upper air way obstruction
      (34.3%), prolonged intubation (20%). Common diagnoses were tumor of
      larynx/hypopharynx (26.3%), infectious causes (20.6%) and cut throat (13.7%).
      CONCLUSIONS: Most common indication for tracheostomy in tertiary care health
      institution in Eastern Nepal was upper airway obstruction. Procedure is safe if
      done properly.

PMID- 25574982
TI  - A study of seven day mortality in acute ischemic stroke in a teaching hospital in
      Chitwan.
AB  - BACKGROUND: Stroke mortality rate indicates a measure in hospital quality care.
      Most of the available data are from developed countries and are for late
      mortality. Only few studies on 7-day fatality, a recently implemented indicator
      of early stoke mortality, are reported. We attempted to identify the predictors
      of clinical outcome by 7th day in acute ischemic stroke. METHODS: This
      descriptive study included 100 consecutive cases of acute ischemic stroke
      admitted to Neurology center of a teaching hospital in Chitwan, Nepal. Common
      risk factors were identified. The cases were classified as per TOAST
      classification and severity at admission assessed using National Institutes of
      Health Stroke Scale. Univariate and multivariate analysis was used to analyze the
      data. RESULTS: Thirteen percent patients expired by 7th day. On univariate
      analysis severity of stroke, fever, atrial fibrillation, hypertension at
      admission and early neurological deterioration were related to early 7-day
      mortality where as age, gender, smoking, diabetes mellitus, coronary artery
      disease, early onset seizures, dyslipidemaia, and hematocrit were unrelated to
      early mortality. Multivariate analysis showed that only NIHS score was
      significantly correlated with early mortality. CONCLUSIONS: A mortality rate of
      13 percent was noted by 7th day. A positive association was noted with stroke
      severity, early neurological deterioration, arterial fibrillation, hypertension
      and fever at onset.

PMID- 25574983
TI  - A comparative study on use of 3% saline versus 0.9% saline nebulization in
      children with bronchiolitis.
AB  - BACKGROUND: Bronchiolitis is a common clinical problem in children below 2 years
      presenting with respiratory symptoms. As there is necrosis and sloughing of
      epithelial cells, edema, increased secretion of mucus causing obstruction of
      large and small airways we aim to see the clinical profile and the effect of use
      of hypertonic (3%) saline nebulization in these children. METHODS: A double blind
      randomized controlled trial was conducted at department of Pediatrics, in a
      hospital from July 2012 to August 2013. The computer generated random number was
      used to select the case and control group. All eligible patients were randomly
      assigned to one of two groups: receiving inhalation of 4 ml normal (0.9%) saline
      or hypertonic (3%) saline. Treating physicians, researchers and nurses were all
      blinded of the solution. Both saline were kept in two identical containers and
      labeled as solution A and solution B. Patients in each group will receive three
      treatments on each day of hospitalization and clinical score were obtained 30
      minutes before each inhalation session. RESULTS: Bronchiolitis accounted 11.26%
      of total admissions. Their mean age (+/-SD) was 8.56 (+/-5.013) months with range
      from 45 days to 24 months. A total of 53 (74%) male were enrolled in the study.
      Fifty-seven (79%) children were less than 12 months and 15 (21%) were 12 months -
      24 months. The mean (+/-SD) for duration of hospital stay was 44.82 (+/-23.15)
      and 43.60 (+/-28.25) for 3% and 0.9% group respectively (p=0.86). Likewise, mean
      (SD) duration of oxygen supplementation was 32.50 (+/-20.44) and 34.50 (+/-26.03)
      for 3% and 0.9% group respectively (p=0.85). Moreover, time required for
      normalization of clinical score was 36.79 (+/-19.53) and 38.34 (+/-26.67) for 3%
      and 0.9% group respectively (p=0.80). CONCLUSIONS: There is no advantage of
      hypertonic saline over normal saline nebulization in the management
      bronchiolitis.

PMID- 25574984
TI  - A comparison of midazolam co-induction with propofol priming in propofol induced
      anesthesia.
AB  - BACKGROUND: Combination therapy with two or more different drugs, with the
      intension of reaching the same therapeutic goal, was heavily criticized for a
      long time. However, it is accepted today, especially when advantage over
      monotherapy can be proved. Our study was undertaken to compare whether propofol
      priming and midazolam predosing would affect total induction dose requirement of
      Propofol. METHODS: A prospective randomized, double blind control study was
      conducted where 120 patients (16-65 years) were divided into 3 groups. Group P
      received 0.4 mg/kg of Propofol, Group M received 0.05 mg/kg of Midazolam and
      Group N received 3 ml of Normal Saline 5 minutes after intravenous pethidine 0.75
      mg / kg given for analgesia. We compared the total dose of propofol requirement
      for induction of anaesthesia in all the 3 groups, taking loss of verbal contact
      as the end point. Additionally, changes in haemodynamic status like blood
      pressure and heart rate at various intervals were studied and compared among the
      groups. RESULTS: The groups were similar in terms of age, sex, weight and
      American Society of Anesesthesiologists Physical Status.The dose of Propofol
      required to induce anesthesia in Midazolam group was 1.58 mg/kg,1.86 mg/kg in
      Propofol group and 1.96 mg/kg in the control group. There were less hemodynamic
      changes in Midazolam group compared to the other two. CONCLUSIONS: Pre-dosing
      with Midazolam is more effective than Propofol priming in reducing the dose of
      Propofol induced anaesthesia associated with minimum hemodynamic alterations.

PMID- 25574985
TI  - Diabetic retinopathy in tessellated fundus.
AB  - BACKGROUND: Duration of diabetes, poor control, age of the patient, frequent
      hypoglycemia, hypercholesterolemia, over-weight, smoking, alcohol, renal failure
      and pregnancy have all been suggested as factors which may influence the onset of
      diabetic retinopathy. However, there are cases without retinopathy in spite of
      duration of 30 to 40 years of diabetes and presence of one or other above
      mentioned risk factors, suggesting role of local factors to prevent
      angiopathy.Our study aims to assess whether tessellated fundus is a protective
      factor for diabetic retinopathy. METHODS: This was hospital based descriptive
      study. The patients included in the study were 40 years and above having diabetes
      for 10 years and beyond. Diabetic retinopathy was graded following Early
      treatment Diabetic retinopathy Study. RESULTS: Tigroid fundus was negatively
      associated with diabetic retinopathy (OR 0.49 with 95% confidence interval 0.21
      1.11) and maculopathy (OR 0.43 with 95% confidence interval 0.15-1.3). Age 40-50
      years (OR 0.67 with 95% confidence interval 0.24-1.83), female gender (OR 0.71
      with confidence interval 0.31-1.61), HbA1c <6.5(OR 0.36 with confidence interval
      0.99-1.31) and duration 10-15 years of onset of diabetes (OR 0.58 with confidence
      interval 0.22-1.37) was negatively associated with diabetic retinopathy in
      tigroid fundus diabetics. Age 40-50 years (OR 2.12 with confidence interval 0.43
      10.5), female gender (OR 2.51 with confidence interval 0.38-10.88), HbA1c<6.5 (OR
      3.12 with confidence interval 0.59-16.58) and duration 10-15 years of onset of
      diabetes (OR 1.5 with confidence interval 0.1-18.54) was positively associated
      with retinopathy in non-tigroid fundus. CONCLUSIONS: Tessellated fundus was
      observed as decreased risk for the development of diabetic retinopathy and
      maculopathy.

PMID- 25574986
TI  - Drug dosage adjustment of patients with impaired renal function at hospital
      discharge in a teaching hospital.
AB  - BACKGROUND: Inappropriate dosing and the risk of toxicities are common with the
      patients with impaired renal function. Therefore, appropriate dosing is
      obligatory to prevent the drug toxicities. The present study was performed to
      investigate the appropriateness of dosage adjustment of the drugs that are toxic
      to kidney and/or metabolized or eliminated (TEM) by kidney. METHODS: A
      retrospective study was performed at the time of hospital discharge in the
      patients with impaired renal function. All patients with renal clearance <=50
      ml/min/1.73 m2 were included for the analysis. Data with respect to patient's
      clinical, medications and their dosages, laboratory findings were extracted from
      medical record section. RESULTS: At discharge, there were a total of 848
      prescribed drugs in 116 impaired renal function patients. Of them 404 were
      classified as TEM medication. Dose adjustment according to renal function was
      judged as necessary in 135 TEM medications and 28 were deemed to be used with
      caution. Among these, 108 (80% of 135) medications were considered appropriate in
      dosing, whereas 27 (20%) were inappropriate. Total 14 (10.37%) and 13 (9.63%)
      times of inappropriate dosing were found in those with moderate and severe renal
      impairment, respectively. The frequency of inappropriate dosing was not
      significantly different from moderate than that of the severe renal impairment (p
      > 0.05). CONCLUSIONS: The results of the study demonstrated that dosage
      adjustment of TEM drugs in patients with impaired renal function is less than
      optimum in a considerable number of patients at hospital discharge. Awareness
      raising and monitoring system for inappropriate dosing is critical to improve the
      quality of care in patients with renal dysfunction.

PMID- 25574987
TI  - Hormonal profile and efficacy of long pulse Nd-YAG laser in treatment of
      hirsutism.
AB  - BACKGROUND: Hormones, particularly androgens play a vital role in hair growth,
      differentiation and distribution. Hirsutism is a common entity among Nepalese
      population with skin types III, IV and V. Long pulsed lasers are commonly used
      for hair removal. METHODS: This is a prospective analytical study done in
      Dhulikhel Hospital Kathmandu University Hospital, Kavre, Nepal from November 2010
      to November 2011. Patients were first subjected to hormonal evaluation.
      Androgens, their tropic hormones, insulin resistance markers and endocrine
      components were measured and compared. Subjects were then categorized into two
      groups according to androgen levels: group A (n=30) with significantly high
      androgen (total testosterone and dehydroepiandrosterone sulfate) or elevated
      luteinizing hormone: follicle stimulating hormone ratio, consistent with
      Polycystic Ovarian Syndrome (PCOS) and group B (n=30). Adrenal tumour was ruled
      out in all patients. All patients received long pulse Nd-YAG laser (50J/cm2; 50
      msec pulse duration) therapy at four weeks interval to achieve at least 50% hair
      reduction. RESULTS: Among group A patients, average 8.1 treatment sessions were
      required for substantial hair reduction, whereas, average 5.7 sessions produced
      similar results in group B patients (p-value <0.05). CONCLUSIONS: Patients with
      high androgen level and elevated LH: FSH ratio requires more treatment sessions
      for hair removal with long pulsed ND-YAG laser than patients with normal or low
      hormone level.

PMID- 25574988
TI  - MRI evaluation of knee injury with arthroscopic correlation.
AB  - BACKGROUND: Magnetic Resonance Imaging has emerged as the primary investigation
      for evaluation of the knee injury because of its high resolution and accuracy and
      it has often been regarded as the noninvasive alternative to diagnostic
      arthroscopy. The objective of this study was to find out the various types of
      traumatic lesions of the knee on MRI, to correlate the results with arthroscopy,
      and to establish the accuracy of MRI in detecting ligament and meniscal injury.
      METHODS: This cross sectional study was conducted on 40 patients with knee injury
      over a period of one year. MRI of the knee followed by arthroscopy was performed
      in each case. Arthroscopy was done within 30 days of MRI examination and was
      considered as gold standard. RESULTS: Various types of lesion seen on MRI were as
      follows: joint effusion 27 (67.5%), anterior cruciate ligament tear 23 (57.5%),
      medial meniscus tear 20 (50%), bone contusion 18 (45%), lateral meniscus tear 16
      (40%), medial collateral ligament injury 16 (40%), lateral collateral ligament
      injury 14 (35%) and posterior cruciate ligament tear 14 (35%). Sensitivity,
      specificity and accuracy of MRI in detecting meniscal and cruciate ligament
      injury were as follows: medial meniscus: 85.7%, 89.4%, 87.5%; for lateral
      meniscus: 83.3%, 95.4%, 90%; for anterior cruciate ligament: 91.3%, 88.2%, 90%;
      and for posterior cruciate ligament: 92.8%, 96.1%, 95% respectively. CONCLUSIONS:
      MRI is a noninvasive, useful and reliable diagnostic tool for evaluating knee
      injury and it can be used as a first line investigation in patients with knee
      injury.

PMID- 25574989
TI  - Intestinal type borderline mucinous ovarian tumour.
AB  - A 26 years old para 4 lady presented with abdominal distension following a home
      delivery 18 months back and lactational amenorrhoea following since. Examination
      and investigation findings revealed a large ovarian tumour (28X28 cm) occupying
      the whole of the abdomen. Tumour markers were normal except for a slightly raised
      lactate dehydrogenase enzyme. Patient underwent staging laparotomy- left
      salpingoophorectomy, right tubal ligation with omental biopsy and peritoneal
      fluid cytology. Histopathology report revealed borderline mucinous ovarian tumour
      of intestinal type. Her postoperative period was uneventful and she was advised
      for follow-up. Borderline ovarian tumours are uncommon tumours. In the younger
      age with stage I, fertility sparing surgery is enough and has excellent
      prognosis, but follow up is important.

PMID- 25574990
TI  - Successful intubation with McCoy laryngoscope in a patient with ankylosing
      spondylitis.
AB  - Involvement of cervical spine in ankylosing spondylitis limits neck movement
      resulting in difficult intubation. We report a case of 45-yr-old lady of
      ankylosing spondylitis with restricted neck movement planned for emergency
      laparotomy. Grade 3 Cormack and Lehane laryngoscopic view was observed with
      Macintosh laryngoscope and gum elastic bougie could not be negotiated. At second
      attempt with McCoy blade, the posterior commissure of the vocal cord could be
      visualized and intubation was successful. Thus, in absence of flexible
      laryngoscopes and when awake intubation is not feasible, McCoy blade should be
      considered an alternative than Macintosh blade to attempt intubation in patients
      of ankylosing spondylitis with restricted neck movement.

PMID- 25574991
TI  - Health research and clinical practice: the present scenario.

PMID- 25574992
TI  - Music preferences of mechanically ventilated patients participating in a
      randomized controlled trial.
AB  - Mechanical ventilation (MV) is a life-saving measure and supportive modality
      utilized to treat patients experiencing respiratory failure. Patients experience
      pain, discomfort, and anxiety as a result of being mechanically ventilated. Music
      listening is a non-pharmacological intervention used to manage these
      psychophysiological symptoms associated with mechanical ventilation. The purpose
      of this secondary analysis was to examine music preferences of 107 MV patients
      enrolled in a randomized clinical trial that implemented a patient-directed music
      listening protocol to help manage the psychophysiological symptom of anxiety.
      Music data presented includes the music genres and instrumentation patients
      identified as their preferred music. Genres preferred include: classical, jazz,
      rock, country, and oldies. Instrumentation preferred include: piano, voice,
      guitar, music with nature sounds, and orchestral music. Analysis of three
      patients' preferred music received throughout the course of the study is
      illustrated to demonstrate the complexity of assessing MV patients and the need
      for an ongoing assessment process.

PMID- 25574994
TI  - Nonlinear microscopy of chitin and chitinous structures: a case study of two cave
      dwelling insects.
AB  - We performed a study of the nonlinear optical properties of chemically purified
      chitin and insect cuticle using two-photon excited autofluorescence (TPEF) and
      second-harmonic generation (SHG) microscopy. Excitation spectrum, fluorescence
      time, polarization sensitivity, and bleaching speed were measured. We have found
      that the maximum autofluorescence signal requires an excitation wavelength below
      850 nm. At longer wavelengths, we were able to penetrate more than 150-um deep
      into the sample through the chitinous structures. The excitation power was kept
      below 10 mW (at the sample) in order to diminish bleaching. The SHG from the
      purified chitin was confirmed by spectral- and time-resolved measurements. Two
      cave-dwelling, depigmented, insect species were analyzed and three-dimensional
      images of the cuticular structures were obtained.

PMID- 25574993
TI  - Comparison of procedures for co-registering scalp-recording locations to
      anatomical magnetic resonance images.
AB  - Functional brain imaging techniques require accurate co-registration to
      anatomical images to precisely identify the areas being activated. Many of them,
      including diffuse optical imaging, rely on scalp-placed recording sensors.
      Fiducial alignment is an effective and rapid method for co-registering scalp
      sensors onto anatomy, but is quite sensitive to placement errors. Surface
      Euclidean distance minimization using the Levenberq-Marquart algorithm (LMA) has
      been shown to be very accurate when based on good initial guesses, such as
      precise fiducial alignment, but its accuracy drops substantially with fiducial
      placement errors. Here we compared fiducial and LMA co-registration methods to a
      new procedure, the iterative closest point-to-plane (ICP2P) method, using
      simulated and real data. An advantage of ICP2P is that it eliminates the need to
      identify fiducials and is, therefore, entirely automatic. We show that,
      typically, ICP2P is as accurate as fiducial-based LMA, but is less sensitive to
      initial placement errors. However, ICP2P is more sensitive to spatially
      correlated noise in the description of the head surface. Hence, the best
      technique for co-registration depends on the type of data available to describe
      the scalp and the surface defined by the recording sensors. Under optimal
      conditions, co-registration error using surface-fitting procedures can be reduced
      to ~ 3 mm.

PMID- 25574996
TI  - Identification of risk factors for cesarean delivery following induction of
      labour.
AB  - BACKGROUND: Induction of labor is one of the most common procedures in
      obstetrics. Induction has been found to both increase and decrease the risk of
      cesarean delivery. Various studies have found different factors in different
      studies. The purpose of this study is to increase our knowledge of factors that
      increase risk of cesarean delivery when labour is induced at term. METHODS: A
      prospective observational study was conducted from June 2006-July 2007 at an
      obstetric unit of Eastern Nepal. A total of 348 patients in a 1:1 ratio (vaginal
      delivered n1-174, cesarean delivered n2-174) were enrolled in the study after
      inclusion and exclusion criteria were met. Logistic regression analysis was done
      to assess the significant variables. RESULTS: Maternal age, height, parity,
      indication of induction, gestational period at induction, presence of meconium in
      amniotic fluid, hypertension were not significantly associated with increased
      risk of cesarean delivery. In an adjusted model only birth weight, prolonged
      latent and active phases of labour, Bishop's score <=5 were significantly
      associated with increased risk of cesarean delivery. CONCLUSIONS: Bishop's score
      <=5 at induction, obesity, three doses of misoprostol required for successful
      induction, use of oxytocin, prolonged latent phase, prolonged active phase, birth
      weight of neonate >4kg was significantly associated with increased risk of
      cesarean in unadjusted model but in an adjusted model only birth weight,
      prolonged latent and active phases of labour, Bishop's score <=5 were
      significantly associated with increased risk of cesarean delivery.

PMID- 25574995
TI  - Age-related variation in foraging behaviour in the wandering albatross at South
      Georgia: no evidence for senescence.
AB  - Age-related variation in demographic rates is now widely documented in wild
      vertebrate systems, and has significant consequences for population and
      evolutionary dynamics. However, the mechanisms underpinning such variation,
      particularly in later life, are less well understood. Foraging efficiency is a
      key determinant of fitness, with implications for individual life history trade
      offs. A variety of faculties known to decline in old age, such as muscular
      function and visual acuity, are likely to influence foraging performance. We
      examine age-related variation in the foraging behaviour of a long-lived, wide
      ranging oceanic seabird, the wandering albatross Diomedea exulans. Using
      miniaturised tracking technologies, we compared foraging trip characteristics of
      birds breeding at Bird Island, South Georgia. Based on movement and immersion
      data collected during the incubation phase of a single breeding season, and from
      extensive tracking data collected in previous years from different stages of the
      breeding cycle, we found limited evidence for age-related variation in commonly
      reported trip parameters, and failed to detect signs of senescent decline. Our
      results contrast with the limited number of past studies that have examined
      foraging behaviour in later life, since these have documented changes in
      performance consistent with senescence. This highlights the importance of studies
      across different wild animal populations to gain a broader perspective on the
      processes driving variation in ageing rates. 

PMID- 25574998
TI  - Patient's perception towards quality nursing care.
AB  - BACKGROUND: Quality nursing care remains an important role for patients because
      nurses are involved in almost every aspect of client's care in hospital. Nurses
      interact with patients more often than any other health care personnel in a
      hospital. Patients express their requirements in terms of what they need, want,
      prefer, expect and demand with respect to the nursing service they receive. The
      main objective of this study was to identify the Patient's Perception towards
      Quality Nursing Care. METHODS: A descriptive quantitative and qualitative
      research design was adopted; study areas were Bir-hospital and Tribhuvan
      University Teaching Hospital (TUTH). Non probability purposive sampling technique
      with semi structured interview questionnaire including Likert Scale was used to
      collect the data. Descriptive and inferential statistics were used for analysis.
      RESULTS: Overall perception of respondents about nursing care (nurses' behavior,
      safety and security and admission procedure) is positive as 182 (91%) perceived
      positively, whereas 18 (9%) perceived negatively (not positive). There is no
      significant difference of perception in relation to total nursing care by sex,
      education and occupation status of the respondents as highest percentage of
      respondents had positive perception. CONCLUSIONS: It can be concluded that most
      of the respondents showed positive attitude towards quality nursing care in both
      hospitals.

PMID- 25574997
TI  - Implementation status of self-assessment/peer-group discussion program: a bottom
      up approach of monitoring/supervision in improving quality of health services.
AB  - BACKGROUND: Monitoring/supervision is an essential component for improving the
      quality of health services including rational use of medicines. A new bottom-up
      approach of monitoring/supervision consisting of self-assessment/ peer-group
      discussion was found to be effective in improving prescribing practices. The new
      strategy significantly improved the prescribing practices based on standard
      treatment guidelines. The government has implemented it as a Program in primary
      health care services of Nepal. This article aims to share the implementation
      status of the self-assessment/peer-group discussion Program for improving the
      prescribing practices of common health problems and availability of drugs in the
      district health system. METHODS: Concurrent mixed research design was applied for
      data collection. The data were collected at different levels of health care
      system using in-depth interviews, participatory observations and documentary
      analysis. RESULTS: The Management Division, Department of Health Services
      implemented the Program in 2009-10 and the PHC Revitalization Division, DoHs is
      the implementation division since 2010-11. The Program comprised revision of
      participant's and trainer's manuals, training of trainers and prescribers,
      finalisation of health conditions and indicators, distribution of carbon copy
      prescription pads, and conduction of peer-group discussions.The Program was
      implemented in number of districts. CONCLUSIONS: The government made the policy
      decision to implement the Program for monitoring prescribing practices and the
      availability of free drugs in districts. However, it has covered only few
      districts and needs escalation to cover all 75 districts of the country.

PMID- 25574999
TI  - Gender differences on risk factors of non-communicable diseases--a community
      based cross-sectional study in central Nepal.
AB  - BACKGROUND: Non-communicable diseases are the leading causes of death globally,
      killing more people each year than all other causes combined. As many other
      developing countries, Nepal is also facing double burden of diseases. The aim of
      present study was to assess gender wise differences on prevalence of risk factors
      of non-communicable diseases. METHODS: This was a community based cross sectional
      study which was based on WHO's STEP approach for surveillance risk factors of non
      communicable diseases among males and females. Multi-staged sampling technique
      was used to get required study sample. Descriptive and inferential statistics
      were applied to compare the risk factors between two genders. RESULTS: More than
      two-fifth of male and one-fifth of female respondents were currently using
      tobacco. The proportion of current alcohol users was found higher among the male
      respondents (28.6%) than their female counterparts (13.6%) (P<0.001). Only 35
      (5.3%) of males and 13 (2.3%) of females were found consuming adequate (>=5
      serving) intake of fruits per day. Study revealed that hypertension was slightly
      higher in male 165 (24.8%) than their female counterparts 111 (19.3%) but
      differences between two genders were statistically not significant. CONCLUSIONS:
      The findings of present study suggest that there is high prevalence of risk
      factors of non-communicable diseases among both sexes in central Nepal. The
      finding emphasises the need for a focused national strategies targeting to tackle
      this modern epidemic of non-communicable diseases by incorporating primordial
      prevention activities to all adult population irrespective to gender.

PMID- 25575000
TI  - Effect of sitting posture on development of scoliosis in Duchenne Muscular
      Dystrophy cases.
AB  - BACKGROUND: Scoliosis is a frequent association in boys with Duchenne Muscular
      Dystrophy when the ability to walk is lost around nine to 12 years of age. This
      study assessed the contribution of physical factors including lumbar posture to
      scoliosis in non-ambulatory youth with DMD in Nepal. METHODS: Linear regression
      was used to assess effects of time since loss of ambulation, muscle strength,
      functional severity and lumbar angle as a binary variable on coronal Cobb angle;
      again logistic regression was used to assess effects of muscle strength and cross
      legged sitting on the presence of a lordotic lumbar posture in 22 non-ambulant
      boys and young men. RESULTS: The boys and young men had a mean (SD) age of 15.1
      (4.0) years, had been non-ambulant for 48.6 (33.8) months and used a median of
      3.5 (range 2 to 7) postures a day. The mean Cobb angle was 15.1 (range 0 to 70)
      degrees. Optimal accuracy in predicting scoliosis was obtained with a lumbar
      angle of -6 degrees  as measured by skin markers, and both a lumbar angle <=-6
      degrees  (P=0.112) and better functional ability (P=0.102) were associated with
      less scoliosis. Use of cross-legged sitting postures during the day was
      associated with a lumbar angle <=-6 degrees  (OR 0.061; 95% CI 0.005 - 0.672;
      P=0.022). CONCLUSIONS: Use of cross-legged sitting posture was associated with
      increase in lumbar lordosis. Higher angle of lumbar lordosis and better
      functional ability are associated with lesser degree of scoliosis.

PMID- 25575001
TI  - Microsurgical free flaps at Kathmandu Model Hospital.
AB  - BACKGROUND: Microsurgery is an emerging subspecialty in Nepal. Microsurgery was
      started at Kathmandu Model Hospital in 2007 with the support from Interplast
      Australia and New Zealand. This study will be useful for establishing a baseline
      for future comparisons of outcome variables and for defining the challenges of
      performing microsurgical free flaps in Nepal. METHODS: A retrospective cross
      sectional study was conducted using the clinical records of all the microsurgical
      free flaps performed at Kathmandu Model Hospital from April 2007 to April 2014.
      RESULTS: Fifty-six free flaps were performed. The commonest indication was
      neoplasm followed by post-burn contracture, infection and trauma. Radial artery
      forearm flap was the commonest flap followed by fibula, antero-lateral thigh,
      rectus, tensor facia lata, lattisimus dorsi, deep inferior epigastric artery
      perforator, and deep circumflex iliac artery flap. Radial artery forearm flaps
      and anterolateral thigh flaps were mostly used for burn contracture
      reconstructions. Twelve of the 13 (92%) fibulae were used for mandibular
      reconstruction for oral cancer and ameloblastoma. Rectus flaps were used mainly
      for covering defects over tibia. Hospital stay ranged from six to 67 days with an
      average of fourteen. Fifteen patients (26%) developed complications. The duration
      of operation ranged from six hours to 10.5 hours with an average of nine hours.
      The longest follow up was for four years. CONCLUSIONS: Microsurgery can be
      started even in very resource-poor center if there is support from advanced
      centers and if there is commitment of the institution and surgical team.

PMID- 25575002
TI  - Fine needle aspiration cytology of neck masses in a hospital.
AB  - BACKGROUND: Fine needle aspiration cytology is a valuable technique in the work
      up of masses arising within neck and represents a screening, inexpensive, and
      rapid technique to sample masses found in neck. METHODS: This study included 117
      cases of neck masses, subjected to fine needle aspiration cytology at the
      department of Pathology of a hospital in Nepal from January 2013 to December
      2013. RESULTS: The study included 117 patients with neck masses with median age
      of 37 years. The majority of the patients were in the age group of 20-29 yrs with
      female predominance. The most frequent cause of neck swelling is lymphadenopathy
      65 (55.6%), followed by thyroid swelling 36 (30.7%), soft tissue lesion 12
      (10.3%) and salivary gland lesions 4 (3.4%). The most common lesion in these
      patients was non-neoplastic, followed by malignant neoplasm. Tuberculosis is the
      most common cause of neck lymphadenopathy and colloid goiter is the commonest
      cause of thyroid swelling. In soft tissue, abscess is the most frequent one.
      Pleomorphic adenoma is more common than other salivary gland lesions.
      CONCLUSIONS: Lymphadenopathy is commonest cause of neck mass, followed by thyroid
      gland & soft tissue swellings. Tuberculosis is the most common diagnosis of neck
      masses, followed by colloid goiter. Fine needle aspiration cytology is pretty
      accurate technique to diagnose neck masses and it is helpful to avoid unnecessary
      surgeries and in general clinical management and it is recommended as a first
      line of investigation in the diagnosis of neck masses.

PMID- 25575003
TI  - Nephron sparing surgery in a tertiary care center in Nepal--an initial
      experience.
AB  - BACKGROUND: Malignant renal mass accounts for 2 to 3% of all malignant diseases
      in adults. Radical surgery used to be the treatment of choice with high
      propensity to develop chronic kidney disease in the compromised contralateral
      kidney. Currently, nephron sparing surgery is considered to be the standard of
      care with equivalent oncological outcome. METHODS: This was a retrospective chart
      review of patients with renal mass less than seven cm in size who had open
      nephron sparing surgery from July 2012 to Sep 2013 at Tribhuvan university
      teaching hospital, Nepal. Latest follow up either from record or over telephone
      was documented. RESULTS: Eight patients (mean age 45 years, male: female
      ratio1:1.6) underwent nephron sparing surgery over the specified period. Mean
      size of tumor was 4.75 cm. Mean ischemia time was 16.37 min. Histopathological
      diagnosis was benign in two and renal cell carcinoma in six patients.
      CONCLUSIONS: Nephron sparing surgery is safe in low stage renal tumors. It also
      prevents unnecessary nephrectomy in benign lesions and prevents negative sequelae
      of long term chronic renal impairment in remaining contralateral kidney.

PMID- 25575004
TI  - Comparison of microdilution and standard agar dilution method for determining
      Penicillin resistance among S.pneumoniae.
AB  - BACKGROUND: Antibiotic resistance among different microbial organisms is
      increasing. No study exists from Pakistan comparing methods of determining
      antibiotic resistance among bacterial isolates. METHODS: Ten clinical patient
      sample strains of S.pneumoniae were used to compare agar dilution with broth
      microdilution method for determining Minimum Inhibitory Concentrations (MICs) of
      Penicillin G. Agar dilution was conducted as per National Committee for Clinical
      Laboratory Standards. Broth microdilution was performed in Brain Heart Infusion
      broth using sterile plastic microtiter trays with 96 U-shaped wells. In both
      methods, concentration of Penicillin G ranged from 0.03 to 16ug/mL and S.aureus
      ATCC 29213 with an MIC of 0.25ug/mL was used as a control. MIC <=0.06ug/mL was
      considered sensitivity to antibiotic, MIC 0.12-1.0 intermediate resistance and
      MIC >=2 full resistance. RESULTS: Good agreement was found between two methods.
      Four strains gave identical MICs in both. The other six strains agreed to within
      one log2 dilution step. Both methods categorized same five strains as Penicillin
      sensitive and four as Penicillin resistant; one strain was classified as
      sensitive on agar dilution but resistant on broth microdilution. Broth
      microdilution was more expensive, tedious and time consuming than the agar
      dilution with multipoint inoculator. This would limit its clinical applicability
      in a busy diagnostic lab with a large sample turnover. CONCLUSIONS: We propose
      agar dilution for the clinical labs in developing countries that use Kirby-Bauer
      disk diffusion method and want to initiate MIC determination of antibiotics for
      patient samples.

PMID- 25575006
TI  - Fine needle aspiration cytology of Kikuchi-Fujimoto disease.
AB  - BACKGROUND: Kikuchi-Fujimoto disease is an acute onset febrile illness of unknown
      etiology, predominantly affecting young women with predilection for cervical
      lymphadenopathy. METHODS: The study included 13 cases of Kikuchi-Fujimoto disease
      with both fine needle aspiration cytology and excisional biopsy of lymph node
      available and data & slides were retrieved from the department of Pathology,
      Tribhuvan University Teaching Hospital and Om Hospital & Research Centre Pvt.
      Ltd., Kathmandu, Nepal from August 2009 to July 2013. RESULTS: The mean age of
      the patients was 27.6 years with a range of 17 to 38 years. Twelve of 13 patients
      had cervical lymphadenopathy. Cytomorphological features included cellularity,
      karyorrhectic debris, crescentichistiocytes, necrosis and cellular polymorphism.
      Histologically, Lymph nodes showed partially effaced architecture by paracortical
      pale foci with karyorrhectic debris. These foci were composed of phagocytic & non
      phagocytic histiocytes, plasmacytoid monocytes, immunoblasts and lymphocytes.
      CONCLUSIONS: Kikuchi-Fujimoto disease, in most cases, can be diagnosed
      cytologically on the basis of identification of karyorrhectic debris and
      crescentic macrophages with reactive background.

PMID- 25575005
TI  - Occurrence of amino acid mutation (Ala98Val) of HNF1alpha in association with
      type II diabetes.
AB  - BACKGROUND: Maturity onset diabetes of the young type 3 is a monogenic form of
      diabetes. Gene defects in the Hepatocyte Nuclear Factor -1 alpha (HNF1a) causes
      MODY3. HNF1a gene located in the chromosome (12q24.2) codes for a transcription
      factor which helps in signalling of insulin exocytosis in pancreatic Beta cells.
      A prevalent amino acid polymorphism at codon 98-Ala98Val (exon 1) of the HNF1a
      was shown to be associated with diabetes in the South Indian population. Since
      Nepal shares the ancestral origin with India and people have been sharing similar
      lifestyles for a long period of life it was relevant to check the occurrence of
      same mutation in diabetic population of Nepal as well. The study was carried out
      to identify the occurrence of amino acid mutation (Ala98Val) of HNF 1 alpha in
      association with type 2 diabetes in diabetic population of Kathmandu. METHODS:
      DNA samples were randomly collected from 12 non-diabetic and 56 diabetic
      patients. The DNA samples were amplified using Polymerase Chain Reaction (PCR).
      Restriction Fragment Length Polymorphism (RFLP) was carried out to identify the
      occurrence of the mutation. RESULTS: During the study, out of 12 non-diabetic
      samples, nine were normal while three samples showed heterozygous Ala98Val
      mutation. Whereas, eight diabetic patients were found to have Ala98Val mutation
      and rest 48 had normal genotype. The study thus showed 16.17% occurence of
      Ala98Val mutation among 68 samples. CONCLUSIONS: The study showed the occurrence
      of Ala98Val amino acid mutation in diabetic samples that were taken under study.

PMID- 25575007
TI  - Review of radiation therapy in benign ocular diseases.
AB  - Radiotherapy is a modality used for the treatment of malignant diseases. However
      it is also used as an effective modality in the treatment of many benign
      disorders. It is generally not the first choice of therapy in non malignant
      conditions but usually used when other modalities have failed or may induce more
      side effects. Benign disorders of the eye can cause severe morbidity in terms of
      inflammatory symptoms, loss of vision, pain and diplopia. Radiotherapy in such
      conditions is given in very low doses and the goals are controlling the condition
      and at the same time minimizing late tissue sequelae, if any. Here we highlight
      the use of radiotherapy in most common benign conditions of the eye; mainly
      Pterygium, Haemangioma, Graves' Orbitopathy and Pseudotumour Orbitae.

PMID- 25575008
TI  - Human genital myiasisin extremes of age.
AB  - Genital myiasis is a very rare entity associated with poor personal hygiene,
      restricted mobility, and immunosuppressed status and ulcerating lesions. With the
      reported incidence of only 0.7%, only a few cases have been published so far in
      literature but none from Nepal. Despite such rare occurrence, we present here two
      such cases which we encountered in an interval of three days; one in an unmarried
      teenager and another in a postmenopausal lady with fungating ulcerative growth of
      vulval carcinoma. Both were successfully managed.

PMID- 25575009
TI  - Laparoscopic management of double gallbladder.
AB  - Double gall bladder is a rare congenital anomaly and is challenging to the
      surgeons due to increased risk of post-operative complications. We present a case
      of double gall bladder that was successfully managed laparoscopically.
      Preoperative ultrasonography showed one vesicle of the gall bladder had thick
      wall with multiple calculi while the other had normal thickness without calculus.
      Both the gallbladders were connected to the common bile duct with a single cystic
      duct.

PMID- 25575010
TI  - Tubercular breast abscess--a diagnostic dilemma.
AB  - Tuberculosis affects many organs, however isolated tubercular breast lesion is
      rare. Clinically as well as radiologically it may mimic both pyogenic abscess and
      malignancy. One such case is being reported where a middle aged woman presented
      with painful, gradually increasing breast lump and was diagnosed clinically,
      radiologically, cytologically and even histologically as pyogenic abscess. Poor
      response to antibiotics raised the suspicion of malignancy for which repeat fine
      needle aspiration cytology was done. Well formed granulomas, necrosis and finally
      demonstration of acid fast bacilli established the diagnosis of tubercular
      abscess. No other organs were involved by tuberculosis in this case. Patient
      responded well to antitubercular drugs. Thus diagnostic challenge lies in the
      demonstration of acid fast bacilli in cases of equivocal morphology in routine
      cytology as well as histology. High clinical suspicion, poor response to
      antibiotics, suggestive radiological findings, cytology, histology and
      demonstration of acid fast bacilli -all contributes to the diagnosis of breast
      tuberculosis.

PMID- 25575012
TI  - Wasp bite.

PMID- 25575011
TI  - Cysticercosis of the tongue.
AB  - Cysticercosis is a condition in which a human being acts as the intermediate host
      of Taenia solium, a pork tape worm. The oral mucosa is an uncommonly involved
      site. A rurally living 35 year old vegetarian female presented with a swelling
      over the right side of her tongue of seven months duration. Histopathology of
      excisional biopsy revealed it to be cysticercosis. Diagnosis of cysticercosis was
      clinically unsuspected. The patient was referred to the general medical clinic
      for further treatment.

PMID- 25575013
TI  - Health care evaluation in Nepal.

PMID- 25575014
TI  - Nylon flocked swab severely reduces Hexagon Obti sensibility.
AB  - Hexagon Obti immunological blood test and flocked swab are widely used in
      forensic laboratories. Nevertheless, up to now, no compatibility tests have been
      published between sampling with the ethylene oxide treated flocked swab and the
      Hexagon Obti blood detection strip. In this study, we investigated this
      compatibility. Our work shows that sampling with ethylene oxide treated flocked
      swab reduces by a factor of at least 100 the detection threshold of blood using
      the Hexagon Obti immunological test. 

PMID- 25575015
TI  - Endocrine disorders in Fanconi anemia: recommendations for screening and
      treatment.
AB  - CONTEXT: Endocrine problems are common in patients with Fanconi anemia (FA).
      About 80% of children and adults with FA have at least one endocrine abnormality,
      including short stature, GH deficiency, abnormal glucose or insulin metabolism,
      dyslipidemia, hypothyroidism, pubertal delay, hypogonadism, or impaired
      fertility. The goal of this report is to provide an overview of endocrine
      abnormalities and guidelines for routine screening and treatment to allow early
      diagnosis and timely intervention. EVIDENCE ACQUISITION: This work is based on a
      comprehensive literature review, including relevant articles published between
      1971 and 2014, and proceedings of a Consensus Conference held by the Fanconi
      Anemia Research Fund in 2013. EVIDENCE SYNTHESIS: The panel of experts collected
      published evidence and discussed its relevance to reflect current information
      about the endocrine care of children and adults with FA before the Consensus
      Conference and through subsequent deliberations that led to the consensus.
      CONCLUSIONS: Individuals with FA should be routinely screened for endocrine
      abnormalities, including evaluation of growth; glucose, insulin, and lipid
      metabolism; thyroid function; puberty; gonadal function; and bone mineral
      metabolism. Inclusion of an endocrinologist as part of the multidisciplinary
      patient care team is key to providing comprehensive care for patients with FA.

PMID- 25575017
TI  - Agricultural intensification exacerbates spillover effects on soil
      biogeochemistry in adjacent forest remnants.
AB  - Land-use intensification is a central element in proposed strategies to address
      global food security. One rationale for accepting the negative consequences of
      land-use intensification for farmland biodiversity is that it could 'spare'
      further expansion of agriculture into remaining natural habitats. However, in
      many regions of the world the only natural habitats that can be spared are
      fragments within landscapes dominated by agriculture. Therefore, land-sparing
      arguments hinge on land-use intensification having low spillover effects into
      adjacent protected areas, otherwise net conservation gains will diminish with
      increasing intensification. We test, for the first time, whether the degree of
      spillover from farmland into adjacent natural habitats scales in magnitude with
      increasing land-use intensity. We identified a continuous land-use intensity
      gradient across pastoral farming systems in New Zealand (based on 13 components
      of farmer input and soil biogeochemistry variables), and measured cumulative off
      site spillover effects of fertilisers and livestock on soil biogeochemistry in 21
      adjacent forest remnants. Ten of 11 measured soil properties differed
      significantly between remnants and intact-forest reference sites, for both fenced
      and unfenced remnants, at both edge and interior. For seven variables, the
      magnitude of effects scaled significantly with magnitude of surrounding land-use
      intensity, through complex interactions with fencing and edge effects. In
      particular, total C, total N, delta15N, total P and heavy-metal contaminants of
      phosphate fertilizers (Cd and U) increased significantly within remnants in
      response to increasing land-use intensity, and these effects were exacerbated in
      unfenced relative to fenced remnants. This suggests movement of livestock into
      surrounding natural habitats is a significant component of agricultural
      spillover, but pervasive changes in soil biogeochemistry still occur through
      nutrient spillover channels alone, even in fenced remnants set aside for
      conservation. These results have important implications for the viability of land
      sparing as a strategy for balancing landscape-level conservation and production
      goals in agricultural landscapes. 

PMID- 25575018
TI  - Distinct neural networks support the mere ownership effect under different
      motivational contexts.
AB  - The "mere ownership effect" refers to individuals' tendency to evaluate objects
      they own more favorably than comparable objects they do not own. There are
      numerous behavioral demonstrations of the mere ownership effect, but the neural
      mechanisms underlying the expression of this self-positivity bias during the
      evaluation of self-associated objects have not been identified. The present study
      aimed to identify the neurobiological expression of the mere ownership effect and
      to assess the potential influence of motivational context. During fMRI scanning,
      participants made evaluations of objects after ownership had been assigned under
      the presence or absence of self-esteem threat. In the absence of threat, the mere
      ownership effect was associated with brain regions implicated in processing
      personal/affective significance and valence (ventromedial prefrontal cortex
      [vMPFC], ventral anterior cingulate cortex [vACC], and medial orbitofrontal
      cortex [mOFC]). In contrast, in the presence of threat, the mere ownership effect
      was associated with brain regions implicated in selective/inhibitory cognitive
      control processes (inferior frontal gyrus [IFG], middle frontal gyrus [MFG], and
      lateral orbitofrontal cortex [lOFC]). These findings indicate that depending on
      motivational context, different neural mechanisms (and thus likely different
      psychological processes) support the behavioral expression of self-positivity
      bias directed toward objects that are associated with the self. 

PMID- 25575016
TI  - Endothelial surface glycocalyx can regulate flow-induced nitric oxide production
      in microvessels in vivo.
AB  - Due to its unique location, the endothelial surface glycocalyx (ESG) at the
      luminal side of the microvessel wall may serve as a mechano-sensor and transducer
      of blood flow and thus regulate endothelial functions. To examine this role of
      the ESG, we used fluorescence microscopy to measure nitric oxide (NO) production
      in post-capillary venules and arterioles of rat mesentery under reduced (low) and
      normal (high) flow conditions, with and without enzyme pretreatment to remove
      heparan sulfate (HS) of the ESG and in the presence of an endothelial nitric
      oxide synthase (eNOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA). Rats (SD, 250
      300 g) were anesthetized. The mesentery was gently taken out from the abdominal
      cavity and arranged on the surface of a glass coverslip for the measurement. An
      individual post-capillary venule or arteriole was cannulated and loaded for 45
      min with 5 MUM 4, 5-Diaminofluorescein diacetate, a membrane permeable
      fluorescent indictor for NO, then the NO production was measured for ~10 min
      under a low flow (~300 MUm/s) and for ~60 min under a high flow (~1000 MUm/s). In
      the 15 min after switching to the high flow, DAF-2-NO fluorescence intensity
      increased to 1.27-fold of its baseline, DAF-2-NO continuously increased under the
      high flow, to 1.53-fold of its baseline in 60 min. Inhibition of eNOS by 1 mM L
      NMMA attenuated the flow-induced NO production to 1.13-fold in 15 min and 1.30
      fold of its baseline in 60 min, respectively. In contrast, no significant
      increase in NO production was observed after switching to the high flow for 60
      min when 1 h pretreatment with 50 mU/mL heparanase III to degrade the ESG was
      applied. Similar NO production was observed in arterioles under low and high
      flows and under eNOS inhibition. Our results suggest that ESG participates in
      endothelial cell mechanosensing and transduction through its heparan sulfate to
      activate eNOS.

PMID- 25575019
TI  - Development and Evaluation of an Educational E-Tool to Help Patients With Non
      Hodgkin's Lymphoma Manage Their Personal Care Pathway.
AB  - BACKGROUND: An overload of health-related information is available for patients
      on numerous websites, guidelines, and information leaflets. However, the
      increasing need for personalized health-related information is currently unmet.
      OBJECTIVE: This study evaluates an educational e-tool for patients with non
      Hodgkin's lymphoma (NHL) designed to meet patient needs with respect to
      personalized and complete health-related information provision. The e-tool aims
      to help NHL patients manage and understand their personal care pathway, by
      providing them with insight into their own care pathway, the possibility to keep
      a diary, and structured health-related information. METHODS: Together with a
      multidisciplinary NHL expert panel, we developed an e-tool consisting of two
      sections: (1) a personal section for patients' own care pathway and their
      experiences, and (2) an informative section including information on NHL. We
      developed an ideal NHL care pathway based on the available (inter)national
      guidelines. The ideal care pathway, including date of first consultation,
      diagnosis, and therapy start, was used to set up the personal care pathway. The
      informative section was developed in collaboration with the patient association,
      Hematon. Regarding participants, 14 patients and 6 laymen were asked to evaluate
      the e-tool. The 24-item questionnaire used discussed issues concerning layout (6
      questions), user convenience (3 questions), menu clarity (3 questions),
      information clarity (5 questions), and general impression (7 questions). In
      addition, the panel members were asked to give their feedback by email. RESULTS:
      A comprehensive overview of diagnostics, treatments, and aftercare can be
      established by patients completing the questions from the personal section. The
      informative section consisted of NHL information regarding NHL in general,
      diagnostics, therapy, aftercare, and waiting times. Regarding participants, 6
      patients and 6 laymen completed the questionnaire. Overall, the feedback was
      positive, with at least 75% satisfaction on each feedback item. Important
      strengths mentioned were the use of a low health-literacy level, the opportunity
      to document the personal care pathway and experiences, and the clear overview of
      the information provided. The added value of the e-tool in general was pointed
      out as very useful for preparing the consultation with one's doctor and for
      providing all information on one website, including the opportunity for a
      personalized care pathway and diary. The majority of the revisions concerned
      wording and clarity. In addition, more explicit information on immunotherapy,
      experimental therapy, and psychosocial support was added. CONCLUSIONS: We have
      developed a personal care management e-tool for NHL patients. This tool contains
      a unique way to help patients manage their personal care pathway and give them
      insight into their NHL by providing health-related information and a personal
      diary. This evaluation showed that our e-tool meets patients' needs concerning
      personalized health-related information, which might serve as a good example for
      other oncologic diseases. Future research should focus on the possible impact of
      the e-tool on doctor-patient communication during consultations.

PMID- 25575021
TI  - Nanoantenna enhancement for telecom-wavelength superconducting single photon
      detectors.
AB  - Superconducting nanowire single photon detectors are rapidly emerging as a key
      infrared photon-counting technology. Two front-side-coupled silver dipole
      nanoantennas, simulated to have resonances at 1480 and 1525 nm, were fabricated
      in a two-step process. An enhancement of 50 to 130% in the system detection
      efficiency was observed when illuminating the antennas. This offers a pathway to
      increasing absorption into superconducting nanowires, creating larger active
      areas, and achieving more efficient detection at longer wavelengths. 

PMID- 25575022
TI  - Radiopaque, iodine functionalized, phenylalanine-based poly(ester urea)s.
AB  - The synthesis and characterization of iodine-functionalized phenylalanine-based
      poly(ester urea)s (PEUs) are reported. 4-Iodo-L-phenylalanine and L-phenylalanine
      were separately reacted with 1,6-hexanediol to produce two monomers, bis-4-I-L
      phenylalanine-1,6-hexanediol-diester (1-IPHE-6 monomer) and bis-L-phenylalanine
      1,6-hexanediol-diester (1-PHE-6 monomer). By varying the feed ratio of the 1-IPHE
      6 and 1-PHE-6 monomers, the copolymer composition was modulated resulting in a
      wide variation in thermal, mechanical and radiopacity properties. Microcomputed
      tomography (MU-CT) projections demonstrate that increasing iodine content results
      in greater X-ray contrast. Compression tests of dry and wet porous scaffolds
      indicate that the poly(1-IPHE-6)0.24-co-poly(1-PHE-6)0.76 material results in the
      highest compression modulus. MC3T3 cell viability and spreading studies show PEUs
      are nontoxic to cells. As most medical device procedures require placement
      verification via fluoroscopic imaging, materials that possess inherent X-ray
      contrast are valuable for a number of applications.

PMID- 25575024
TI  - Next-generation genome-scale models for metabolic engineering.
AB  - Constraint-based reconstruction and analysis (COBRA) methods have become widely
      used tools for metabolic engineering in both academic and industrial
      laboratories. By employing a genome-scale in silico representation of the
      metabolic network of a host organism, COBRA methods can be used to predict
      optimal genetic modifications that improve the rate and yield of chemical
      production. A new generation of COBRA models and methods is now being developed-
      encompassing many biological processes and simulation strategies-and next
      generation models enable new types of predictions. Here, three key examples of
      applying COBRA methods to strain optimization are presented and discussed. Then,
      an outlook is provided on the next generation of COBRA models and the new types
      of predictions they will enable for systems metabolic engineering.

PMID- 25575023
TI  - Innate sensing of microbial products promotes wound-induced skin cancer.
AB  - The association between tissue damage, chronic inflammation and cancer is well
      known. However, the underlying mechanisms are unclear. Here we characterize a
      mouse model in which constitutive epidermal extracellular-signal-regulated kinase
      MAP-kinase signalling results in epidermal inflammation, and skin wounding
      induces tumours. We show that tumour incidence correlates with wound size and
      inflammatory infiltrate. Ablation of tumour necrosis factor receptor (TNFR)-1/-2,
      Myeloid Differentiation primary response gene 88 or Toll-like receptor (TLR)-5,
      the bacterial flagellin receptor, but not other innate immune sensors, in
      radiosensitive leukocytes protects against tumour formation. Antibiotic treatment
      inhibits, whereas injection of flagellin induces, tumours in a TLR-5-dependent
      manner. TLR-5 is also involved in chemical-induced skin carcinogenesis in wild
      type mice. Leukocytic TLR-5 signalling mediates upregulation of the alarmin HMGB1
      (High Mobility Group Box 1) in wound-induced papillomas. HMGB1 is elevated in
      tumours of patients with Recessive Dystrophic Epidermolysis Bullosa, a disease
      characterized by chronic skin damage. We conclude that in our experimental model
      the combination of bacteria, chronic inflammation and wounding cooperate to
      trigger skin cancer. 

PMID- 25575025
TI  - Persistence of frequently transmitted drug-resistant HIV-1 variants can be
      explained by high viral replication capacity.
AB  - BACKGROUND: In approximately 10% of newly diagnosed individuals in Europe, HIV-1
      variants harboring transmitted drug resistance mutations (TDRM) are detected. For
      some TDRM it has been shown that they revert to wild type while other mutations
      persist in the absence of therapy. To understand the mechanisms explaining
      persistence we investigated the in vivo evolution of frequently transmitted HIV-1
      variants and their impact on in vitro replicative capacity. RESULTS: We selected
      31 individuals infected with HIV-1 harboring frequently observed TDRM such as
      M41L or K103N in reverse transcriptase (RT) or M46L in protease. In all these
      samples, polymorphisms at non-TDRM positions were present at baseline (median
      protease: 5, RT: 6). Extensive analysis of viral evolution of protease and RT
      demonstrated that the majority of TDRM (51/55) persisted for at least a year and
      even up to eight years in the plasma. During follow-up only limited selection of
      additional polymorphisms was observed (median: 1).To investigate the impact of
      frequently observed TDRM on the replication capacity, mutant viruses were
      constructed with the most frequently encountered TDRM as site-directed mutants in
      the genetic background of the lab strain HXB2. In addition, viruses containing
      patient-derived protease or RT harboring similar TDRM were made. The replicative
      capacity of all viral variants was determined by infecting peripheral blood
      mononuclear cells and subsequently monitoring virus replication. The majority of
      site-directed mutations (M46I/M46L in protease and M41L, M41L + T215Y and K103N
      in RT) decreased viral replicative capacity; only protease mutation L90M did not
      hamper viral replication. Interestingly, most patient-derived viruses had a
      higher in vitro replicative capacity than the corresponding site-directed mutant
      viruses. CONCLUSIONS: We demonstrate limited in vivo evolution of protease and RT
      harbouring frequently observed TDRM in the plasma. This is in line with the high
      in vitro replication capacity of patient-derived viruses harbouring TDRM compared
      to site-directed mutant viruses harbouring TDRM. As site-directed mutant viruses
      have a lower replication capacity than the patient-derived viruses with similar
      mutational patterns, we propose that (baseline) polymorphisms function as
      compensatory mutations improving viral replication capacity.

PMID- 25575026
TI  - Interaction between calpain-1 and HSP90: new insights into the regulation of
      localization and activity of the protease.
AB  - Here we demonstrate that heat shock protein 90 (HSP90) interacts with calpain-1,
      but not with calpain-2, and forms a discrete complex in which the protease
      maintains its catalytic activity, although with a lower affinity for Ca2+.
      Equilibrium gel distribution experiments show that this complex is composed by an
      equal number of molecules of each protein partner. Moreover, in resting cells,
      cytosolic calpain-1 is completely associated with HSP90. Since calpain-1, in
      association with HSP90, retains its proteolytic activity, and the chaperone is
      displaced by calpastatin also in the absence of Ca2+, the catalytic cleft of the
      protease is not involved in this association. Thus, calpain-1 can form two
      distinct complexes depending on the availability of calpastatin in the cytosol.
      The occurrence of a complex between HSP90 and calpain-1, in which the protease is
      still activable, can prevent the complete inhibition of the protease even in the
      presence of high calpastatin levels. We also demonstrate that in basal cell
      conditions HSP90 and calpain-1, but not calpain-2, are inserted in the multi
      protein N-Methyl-D-Aspartate receptor (NMDAR) complex. The amount of calpain-1 at
      the NMDAR cluster is not modified in conditions of increased [Ca2+]i, and this
      resident protease is involved in the processing of NMDAR components. Finally, the
      amount of calpain-1 associated with NMDAR cluster is independent from Ca2+
      mediated translocation. Our findings show that HSP90 plays an important role in
      maintaining a given and proper amount of calpain-1 at the functional sites. 

PMID- 25575028
TI  - Fine particulate matter components and emergency department visits for
      cardiovascular and respiratory diseases in the St. Louis, Missouri-Illinois,
      metropolitan area.
AB  - BACKGROUND: Given that fine particulate matter (<= 2.5 MUm; PM2.5) is a mixture
      of multiple components, it has been of high interest to identify its specific
      health-relevant physical and/or chemical features. OBJECTIVES: We conducted a
      time-series study of PM2.5 and cardiorespiratory emergency department (ED) visits
      in the St. Louis, Missouri-Illinois metropolitan area, using 2 years of daily
      PM2.5 and PM2.5 component measurements (including ions, carbon, particle-phase
      organic compounds, and elements) made at the St. Louis-Midwest Supersite, a
      monitoring site of the U.S. Environmental Protection Agency Supersites ambient
      air monitoring research program. METHODS: Using Poisson generalized linear
      models, we assessed short-term associations between daily cardiorespiratory ED
      visit counts and daily levels of 24 selected pollutants. Associations were
      estimated for interquartile range changes in each pollutant. To allow comparison
      of relationships among multiple pollutants and outcomes with potentially
      different lag structures, we used 3-day unconstrained distributed lag models
      controlling for time trends and meteorology. RESULTS: Considering results of our
      primary models, as well as sensitivity analyses and models assessing co-pollutant
      confounding, we observed robust associations of cardiovascular disease visits
      with 17alpha(H),21beta(H)-hopane and congestive heart failure visits with
      elemental carbon. We also observed a robust association of respiratory disease
      visits with ozone. For asthma/wheeze, associations were strongest with ozone and
      nitrogen dioxide; observed associations of asthma/wheeze with PM2.5 and its
      components were attenuated in two-pollutant models with these gases. Differential
      measurement error due to differential patterns of spatiotemporal variability may
      have influenced patterns of observed associations across pollutants. CONCLUSIONS:
      Our findings add to the growing field examining the health effects of PM2.5
      components. Combustion-related components of the pollutant mix showed
      particularly strong associations with cardiorespiratory ED visit outcomes.

PMID- 25575029
TI  - Nitrogen-doped Fe/Fe3C@graphitic layer/carbon nanotube hybrids derived from MOFs:
      efficient bifunctional electrocatalysts for ORR and OER.
AB  - A novel nitrogen-doped Fe/Fe3C@graphitic layer/carbon nanotube hybrid derived
      from MOFs has been first fabricated by a facile approach. The hybrid exhibited
      outstanding bifunctional electrocatalytic activity for ORR and OER, due to the
      merits of graphitic layer/carbon nanotube structures with highly active N and
      Fe/Fe3C sites. 

PMID- 25575027
TI  - Do pollinators contribute to nutritional health?
AB  - Despite suggestions that animal pollinators are crucial for human nutritional
      health, no studies have actually tested this claim. Here, we combined data on
      crop pollination requirements, food nutrient densities, and actual human diets to
      predict the effects of pollinator losses on the risk of nutrient deficiency. In
      four developing countries and across five nutrients, we found that 0 to 56% of
      populations would become newly at risk if pollinators were removed. Increases in
      risk were most pronounced for vitamin A in populations with moderate levels of
      total nutrient intake. Overall, the effects of pollinator decline varied widely
      among populations and nutrients. We conclude that the importance of pollinators
      to human nutrition depends critically on the composition of local diets, and
      cannot be reliably predicted from global commodity analyses. We identify
      conditions under which severe health effects of pollinator loss are most likely
      to occur. 

PMID- 25575030
TI  - Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam:
      a systematic review and meta-analysis.
AB  - OBJECTIVES: A better dosing strategy can improve clinical outcomes for patients.
      We sought to compare the extended or continuous infusion with conventional
      intermittent infusion of piperacillin/tazobactam, investigating which approach is
      better and worthy of recommendation for clinical use. METHODS: Articles were
      gathered from PubMed, Web of Science, ProQuest, Science Direct, Cochrane, two
      Chinese literature databases (CNKI, Wan Fang Data) and related ICAAC and ACCP
      conferences. Randomized controlled and observational studies that compared
      extended or continuous infusion with conventional intermittent infusion of
      piperacillin/tazobactam were identified from the databases above and analyzed.
      Two reviewers independently extracted and investigated the data. A meta-analysis
      was performed using Revman 5.2 software. The quality of each study was assessed.
      Sensitivity analysis and publication bias were evaluated. RESULTS: Five
      randomized controlled trials and nine observational studies were included in this
      study. All included studies had high quality and no publication bias was found.
      Compared to the conventional intermittent infusion approach, the extended or
      continuous infusion group had a significantly higher clinical cure rate (OR 1.88,
      95% CI 1.29-2.73, P = 0.0009) and a lower mortality rate (OR 0.67, 95% CI 0.50
      0.89, P = 0.005). No statistical difference was observed for bacteriologic cure
      (OR 1.40, 95% CI 0.82-2.37, P = 0.22) between the two dosing regimens. The
      sensitivity analysis showed the results were stable. CONCLUSIONS: Our systematic
      review and meta-analysis suggested that the extended or continuous infusion
      strategy of piperacillin/tazobactam should be recommended for clinical use
      considering its higher clinical cure rate and lower mortality rate in comparison
      with conventional intermittent strategy. Data from this study could be
      extrapolated for other beta-lactam antimicrobials. Therefore, this dosing
      strategy could be considered in clinical practice.

PMID- 25575032
TI  - Current state of prognostication and risk stratification in myelodysplastic
      syndromes.
AB  - PURPOSE OF REVIEW: Myelodysplastic syndromes (MDS) are characterized by
      significant biologic and clinical heterogeneity. Because of the wide outcome
      variability, accurate prognostication is vital to high-quality risk-adaptive care
      of MDS patients. In this review, we discuss the current state of prognostic
      schemes for MDS and overview efforts aimed at utilizing molecular aberrations for
      prognostication in clinical practice. RECENT FINDINGS: Several prognostic
      instruments have been developed and validated with increasing accuracy and
      complexity. Oncologists should be aware of the inherent limitations of these
      prognostic tools as they counsel patients and make clinical decisions. As more
      therapies are becoming available for MDS, the focus of model development is
      shifting from prognostic to treatment-specific predictive instruments. In
      addition to providing additional prognostic data beyond traditional clinical and
      pathologic parameters, the improved understanding of the genetic landscape and
      pathophysiologic consequences in MDS may allow the construction of treatment
      specific predictive instruments. SUMMARY: How to best use the results of
      molecular mutation testing to inform clinical decision making in MDS is still a
      work in progress. Important steps in this direction include standardization in
      performance and interpretation of assays and better understanding of the
      independent prognostic importance of the recurrent mutations, especially the less
      frequent ones.

PMID- 25575033
TI  - Novel strategies to prevent relapse after allogeneic haematopoietic stem cell
      transplantation for acute myeloid leukaemia and myelodysplastic syndromes.
AB  - PURPOSE OF REVIEW: Relapse of haematological neoplasms after allogeneic
      haematopoietic stem cell transplantation (HSCT) remains one of the leading causes
      of death. Treatment of relapse post-HSCT is frequently ineffective and outcomes
      are poor, necessitating preventive strategies that are reviewed below. RECENT
      FINDINGS: Current strategies to prevent relapse after HSCT are geared towards
      four general principles: improving the antitumour effects of conditioning
      regimens prior to HSCT, improving graft selection and engineering to augment the
      graft-versus-leukaemia effect, post-HSCT chemotherapeutic interventions to impair
      growth of residual clonal cells and post-HSCT immune-mediated interventions to
      enhance the graft-versus-leukaemia effect. Strategies based on cell manipulation,
      namely natural killer (NK) cell enrichment and adoptive T cell transfer, are
      emerging. Targeted therapies including vaccinations, FLT3 inhibitors, mAbs and
      chimeric antigen receptor T cell therapy represent a new avenue of treating acute
      myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Studies are underway
      to incorporate all of these strategies in the clinical setting to determine their
      impact on relapse and survival after HSCT. SUMMARY: The most recent evidence
      suggests that strategies using NK cell therapy and targeted immune therapies
      after HSCT may change the current landscape of HSCT for AML and MDS.

PMID- 25575031
TI  - Geographical variation in dementia: examining the role of environmental factors
      in Sweden and Scotland.
AB  - BACKGROUND: This study aimed to estimate the magnitude of geographical variation
      in dementia rates and suggest explanations for this variation. Small-area studies
      are scarce, and none has adequately investigated the relative contribution of
      genetic and environmental factors to the distribution of dementia. METHODS: We
      present 2 complementary small-area hierarchical Bayesian disease-mapping studies
      using the comprehensive Swedish Twin Registry (n = 27,680) and the 1932 Scottish
      Mental Survey cohort (n = 37,597). The twin study allowed us to examine the
      effect of unshared environmental factors. The Scottish Mental Survey study
      allowed us to examine various epochs in the life course-approximately age 11
      years and adulthood. RESULTS: We found a 2- to 3-fold geographical variation in
      dementia odds in Sweden, after twin random effects-likely to capture genetic and
      shared environmental variance-were removed. In Scotland, we found no variation in
      dementia odds in childhood but substantial variation, following a broadly similar
      pattern to Sweden, by adulthood. CONCLUSIONS: There is geographical variation in
      dementia rates. Most of this variation is likely to result from unshared
      environmental factors that have their effect in adolescence or later. Further
      work is required to confirm these findings and identify any potentially
      modifiable socioenvironmental risk factors for dementia responsible for this
      geographical variation in risk. However, if these factors do exist and could be
      optimized in the whole population, our results suggest that dementia rates could
      be halved.

PMID- 25575034
TI  - Cutting the cord from myelodysplastic syndromes: chronic myelomonocytic leukemia
      specific biology and management strategies.
AB  - PURPOSE OF REVIEW: Chronic myelomonocytic leukemia (CMML) is a troublesome
      hematologic malignancy characterized by peripheral blood monocytosis, marrow
      dysplasia, cytopenias, frequent extramedullary involvement by clonal cells, and a
      propensity for progression to acute myeloid leukemia. Although previously
      considered a subtype of the myelodysplastic syndromes (MDS), CMML is now
      recognized as a distinct entity with unique biologic and clinical features. This
      change has created a scientific and clinical research landscape that makes it
      difficult to discern CMML-specific validated conclusions versus speculative
      extrapolation from more general MDS data. RECENT FINDINGS: Here, we review recent
      biologic observations that support the current CMML WHO classification, such as
      the high frequency of SRSF2 and ASXL1 mutations compared with MDS and critical
      dependence of CMML cells on granulocyte-macrophage colony-stimulating factor
      signaling. In addition, we discuss CMML-specific prognostic tools and therapeutic
      results of agents developed for MDS in patients with CMML. SUMMARY: The present
      review focuses on evidence supporting CMML ontology and identifies key clinical
      differences in the management of CMML and that of MDS subtypes.

PMID- 25575035
TI  - Preleukemia: the normal side of cancer.
AB  - PURPOSE OF REVIEW: In the present review, we will define the preleukemic state.
      We aim at increasing awareness and research in the field of preleukemia that will
      nurture targeted therapy for the earlier steps of leukemia evolution. RECENT
      FINDINGS: Emerging evidence supports the role of hematopoietic stem/progenitor
      cells carrying recurrent leukemia-related mutations as the cell of origin of both
      myeloid and lymphoid malignancies. The preleukemic stem cells can maintain at
      least to some extent their functionality; however, they have increased fitness
      endowed by the preleukemic mutations that lead to clonal expansion. SUMMARY: The
      latent preleukemic period before overt leukemia presents can take years, and the
      majority of carriers will never develop leukemia in their lifetime. The
      preleukemic state is not rare, with greater than 1% of individuals having
      acquired one or more of the recognized preleukemic lesions. The high frequency of
      such abnormalities in the population may be the cost of growing old; however,
      another view could be that in order to survive to old age, the hematopoietic
      system must adapt to create robust hematopoietic stem/progenitor cells with an
      increased fitness and clonal expansion. Hence, leukemia does not necessarily
      start as a disease, but rather as a need, with the normally functioning
      preleukemic hematopoietic stem cells trying to maintain health for years but in
      time succumbing to their own acquired virtues.

PMID- 25575036
TI  - Chronic neutrophilic leukemia: novel mutations and their impact on clinical
      practice.
AB  - PURPOSE OF REVIEW: Chronic neutrophilic leukemia (CNL) is a rare BCR-ABL1
      negative myeloid malignancy that is characterized by mature granulocytosis
      without dysgranulopoiesis. Differential diagnosis of CNL includes reactive or
      secondary granulocytosis and other myeloid neoplasms, such as atypical chronic
      myeloid leukemia (aCML) and chronic myelomonocytic leukemia (CMML). Herein, we
      focus on recently described mutations in CNL and their impact on diagnosis,
      prognosis and treatment. RECENT FINDINGS: In 2013, membrane-proximal CSF3R
      mutations, most frequently CSF3RT618I, were described in CNL and aCML. Subsequent
      studies confirmed the presence of such mutations in nearly all patients with CNL
      but not in aCML. Furthermore, the majority of the patients with CSF3R-mutated CNL
      also expressed other mutations, such as SETBP1 and ASXL1, which might be
      prognostically detrimental. Laboratory studies revealed that CSF3RT618I induced
      JAK inhibitor-sensitive activation of JAK-STAT and CNL-like disease in mice. Case
      reports have indicated palliative but not disease-modifying activity of JAK
      inhibitor therapy in CSF3R-mutated CNL. SUMMARY: CNL is now a morphologically and
      molecularly defined myeloid malignancy, and no longer a diagnosis of exclusion.
      The identification of CNL-specific molecular markers provides a much needed
      pathogenetic insight and also offers the opportunity to revise current diagnostic
      criteria and identify prognostic biomarkers and potential drug targets.

PMID- 25575037
TI  - Approach to patients with primary refractory acute myeloid leukemia.
AB  - PURPOSE OF REVIEW: Despite successful remission induction in 60-80% of patients
      with newly diagnosed acute myeloid leukemia, there remain a significant number of
      patients who exhibit primary refractory disease. Here we examine the data for
      predicting likelihood of having refractory disease, available therapeutic
      options, and how to decide the appropriate treatment option for a patient. RECENT
      FINDINGS: Recently identified recurrent molecular mutations and early response to
      chemotherapy as determined by kinetics of peripheral blast clearance or nadir
      bone marrow biopsy assist in determining the likelihood of primary refractory
      disease. Newer cytotoxic agents, used as salvage chemotherapy, or in novel
      conditioning regimens for hematopoietic stem cell transplant may represent
      improvement over prior regimens. FMS-like tyrosine kinase 3 gene inhibitors and
      other targeted therapies currently in clinical trials show promise for select
      patients. Hypomethylating agents provide benefit to patients who are not
      candidates for other therapies. SUMMARY: Recent advances in understanding the
      pathogenesis of acute myeloid leukemia have not yet translated to a significantly
      improved outlook for patients with refractory disease. While there are several
      therapeutic options, outcomes remain poor and further studies are needed to
      identify and validate novel approaches.

PMID- 25575038
TI  - Introducing minimal residual disease in acute myeloid leukemia.
AB  - PURPOSE OF REVIEW: Acute myeloid leukemia (AML) is a heterogeneous disease.
      Detection of minimal residual disease (MRD) has the potential to improve risk
      stratification, and its routine monitoring may allow timely therapeutic actions
      such as allogeneic hematopoietic stem cell transplantation. The current review
      will discuss challenges and available evidence for clinical application of MRD
      detection in AML management. RECENT FINDINGS: The heterogeneous nature of AML,
      variations in genetic aberrations and immunophenotypes among patients and between
      malignant subclones coexisting within a single patient, is a challenge for the
      development of a reliable MRD test in AML. MRD value was demonstrated in subtypes
      of AML in which reliable leukemia-specific genetic marker is present (e.g., core
      binding leukemia, AML positive for NPM1 mutation). Multicolor flow cytometry and
      quantitative PCR monitoring for Wilms tumor 1 gene transcript have also been
      shown to correlate with disease progression. MRD results should always be
      interpreted within patient-specific clinical context considering other risk
      factors and timing of MRD eradication. SUMMARY: Introduction of MRD testing into
      routine clinical practice is a challenge in AML. An improvement in laboratory
      techniques along with identification of additional leukemia-specific markers is
      required.

PMID- 25575040
TI  - Organocatalytic enamine-activation of cyclopropanes for highly stereoselective
      formation of cyclobutanes.
AB  - A novel organocatalytic activation mode of cyclopropanes is presented. The
      reaction concept is based on a design in which a reactive donor-acceptor
      cyclopropane intermediate is generated by in situ condensation of
      cyclopropylacetaldehydes with an aminocatalyst. The mechanism of this enamine
      based activation of cyclopropylacetaldehydes is investigated by the application
      of a combined computational and experimental approach. The activation can be
      traced to a favorable orbital interaction between the pi-orbital of the enamine
      and the sigma*C-C orbital of the cyclopropyl ring. Furthermore, the synthetic
      potential of the developed system has been evaluated. By the application of a
      chiral secondary amine catalyst, the organocatalytically activated cyclopropanes
      show an unexpected and highly stereoselective formation of cyclobutanes,
      functionalizing at the usually inert sites of the donor-acceptor cyclopropane. By
      the application of 3-olefinic oxindoles and benzofuranone, biologically relevant
      spirocyclobutaneoxindoles and spirocyclobutanebenzofuranone can be obtained in
      good yields, high diastereomeric ratios, and excellent enantiomeric excesses. The
      mechanism of the reaction is discussed and two mechanistic proposals are
      presented. 

PMID- 25575039
TI  - Daily intake of bisphenol A and triclosan and their association with
      anthropometric data, thyroid hormones and weight loss in overweight and obese
      individuals.
AB  - Bisphenol A (BPA) and triclosan (TCS) were determined in urine of Belgian
      overweight and obese (n=151) and lean (n=43) individuals. After the first urine
      collection (0M), obese patients started a diet program or have undergone
      bariatric surgery. Hereafter, three additional urine samples from obese patients
      were collected after 3 (3M), 6 (6M) and 12 (12M) months. Both compounds were
      detected in >99% of the samples. BPA had median concentrations of 1.7 and
      1.2ng/mL in obese and lean groups, respectively, while TCS had median
      concentrations of 1.5 and 0.9ng/mL in the obese and lean groups, respectively.
      The obese group had higher urinary concentrations (ng/mL) of BPA (p<0.5), while
      no significant differences were found for TCS between the obese and lean groups.
      No time trends between the different collection moments were observed. The BPA
      concentrations in the obese group were negatively associated with age, while no
      gender difference or relationship with body mass index was observed. For TCS, no
      relationships with gender, BMI, or age were found. The temporal variability of
      BPA and TCS was assessed with calculation of the intraclass correlation
      coefficient, Spearman rank correlation coefficients, and surrogate category
      analysis. We observed evidence that single spot urine samples might be predictive
      of exposure over a longer period of time. Dietary intakes of BPA and TCS did not
      differ significantly among the time points considered after obese individuals
      started losing weight (6 and 12months). Multiple linear regression analyses after
      adjusting for age and weight loss revealed negative associations between urinary
      TCS and serum FT4 in the 0M and 3M female obese individuals and positive
      associations between urinary BPA and serum TSH in the lean group. 

PMID- 25575042
TI  - Synthesis of 4-quinolones via a carbonylative Sonogashira cross-coupling using
      molybdenum hexacarbonyl as a CO source.
AB  - A palladium-catalyzed CO gas-free carbonylative Sonogashira/cyclization sequence
      for the preparation of functionalized 4-quinolones from 2-iodoanilines and
      alkynes via two different protocols is described. The first method (A) yields the
      cyclized products after only 20 min of microwave (MW) heating at 120  degrees C.
      The second method (B) is a gas-free one-pot two-step sequence which runs at room
      temperature, allowing the use of sensitive substituents (e.g., nitro and bromide
      groups). For both protocols, molybdenum hexacarbonyl was used as a solid source
      of CO. 

PMID- 25575041
TI  - Metformin Does Not Predict for Prostate Cancer Diagnosis, Grade, or Volume of
      Disease After Transperineal Template-guided Mapping Biopsy.
AB  - OBJECTIVES: Previous studies have evaluated whether metformin is associated with
      prostate cancer incidence and outcomes with conflicting conclusions. In this
      study, we evaluate the incidence of prostate cancer in diabetic patients treated
      with and without metformin compared with nondiabetic patients. MATERIALS AND
      METHODS: One thousand thirty-four patients underwent transperineal template
      guided mapping biopsy secondary to either an elevated prostate-specific antigen
      (PSA) or a prior biopsy finding of atypical small acinar proliferation/prostatic
      intraepithelial neoplasia. The cohort included 881 nondiabetic men, 65 diabetic
      men treated with metformin, and 88 diabetic men not receiving metformin. In
      metformin-treated patients, the median duration of usage was 6.0 years.
      Differences in prostate cancer diagnosis, histologic grade, and tumor volume were
      compared across the 3 cohorts. RESULTS: There was no statistically significant
      differences discerned between the 3 cohorts in patient age, prebiopsy PSA,
      prostate volume, PSA density, PSA doubling time, PSA velocity, or the total
      number of prior transrectal ultrasound biopsy sessions. Five hundred eighty-four
      patients were diagnosed with prostate cancer. There was no difference in prostate
      cancer diagnosis (P=0.153), Gleason score (P=0.960), the number of positive
      biopsy cores (P=0.764), or risk group stratification (P=0.877) between the 3
      cohorts. In multivariate analysis, only older age predicted for prostate cancer
      diagnosis. In terms of Gleason score >=7, patient age, PSA velocity, and body
      mass index predicted for more aggressive histology. Neither diabetes, metformin
      use or duration was of statistical consequence. CONCLUSION: Metformin did not
      impact incidence of prostate cancer diagnosis, Gleason score distribution, or
      volume of disease.

PMID- 25575046
TI  - Foods for Special Dietary Needs: Non-dairy Plant-based Milk Substitutes and
      Fermented Dairy-type Products.
AB  - A growing number of consumers opt for plant-based milk substitutes for medical
      reasons or as a lifestyle choice. Medical reasons include lactose intolerance,
      with a worldwide prevalence of 75%, and cow's milk allergy. Also, in countries
      where mammal milk is scarce and expensive, plant milk substitutes serve as a more
      affordable option. However, many of these products have sensory characteristics
      objectionable to the mainstream western palate. Technologically, plant milk
      substitutes are suspensions of dissolved and disintegrated plant material in
      water, resembling cow's milk in appearance. They are manufactured by extracting
      the plant material in water, separating the liquid, and formulating the final
      product. Homogenization and thermal treatments are necessary to improve the
      suspension and microbial stabilities of commercial products that can be consumed
      as such or be further processed into fermented dairy-type products. The
      nutritional properties depend on the plant source, processing, and fortification.
      As some products have extremely low protein and calcium contents, consumer
      awareness is important when plant milk substitutes are used to replace cow's milk
      in the diet, e.g. in the case of dairy intolerances. If formulated into palatable
      and nutritionally adequate products, plant-based substitutes can offer a
      sustainable alternative to dairy products. 

PMID- 25575045
TI  - Superconductor-insulator transition in quasi-one-dimensional single-crystal
      Nb2PdS5 nanowires.
AB  - Superconductor-insulator transition (SIT) in one-dimensional (1D) nanowires
      attracts great attention in the past decade and remains an open question since
      contrasting results were reported in nanowires with different morphologies (i.e.,
      granular, polycrystalline, or amorphous) or environments. Nb2PdS5 is a recently
      discovered low-dimensional superconductor with typical quasi-1D chain structure.
      By decreasing the wire diameter in the range of 100-300 nm, we observed a clear
      SIT with a 1D transport character driven by both the cross-sectional area and
      external magnetic field. We also found that the upper critical magnetic field
      (Hc2) decreases with the reduction of nanowire cross-sectional area. The
      temperature dependence of the resistance below Tc can be described by the
      thermally activated phase slip (TAPS) theory without any signature of quantum
      phase slips (QPS). These findings demonstrated that the enhanced Coulomb
      interactions with the shrinkage of the wire diameter competes with the interchain
      Josephson-like coupling may play a crucial role on the SIT in quasi-1D system. 

PMID- 25575047
TI  - Tandem intercalation strategy for single-layer nanosheets as an effective
      alternative to conventional exfoliation processes.
AB  - Simple and effective generation of transition metal chalcogenides (TMCs) in a
      single-layer form has been a challenging task. Here we present a tandem molecular
      intercalation (TMI) as a new exfoliation concept for producing single-layer TMCs
      from multi-layer colloidal TMC nanostructures in solution phase. TMI requires
      tandem Lewis base intercalates, where short 'initiator' molecules first
      intercalate into TMCs to open up the interlayer gap, and the long 'primary'
      molecules then bring the gap to full width so that a random mixture of
      intercalates overcomes the interlayer force. Spontaneous exfoliation then yields
      single-layer TMCs. The TMI process is uniquely advantageous because it works in a
      simple one-step process under safe and mild conditions (that is, room temperature
      without sonication or H2 generation). With the appropriate intercalates, we have
      successfully generated single-layer nanostructures of group IV (TiS2, ZrS2),
      group V (NbS2) and VI (WSe2, MoS2) TMCs. 

PMID- 25575044
TI  - The association between daytime napping and cognitive functioning in chronic
      fatigue syndrome.
AB  - OBJECTIVES: The precise relationship between sleep and physical and mental
      functioning in chronic fatigue syndrome (CFS) has not been examined directly, nor
      has the impact of daytime napping. This study aimed to examine self-reported
      sleep in patients with CFS and explore whether sleep quality and daytime napping,
      specific patient characteristics (gender, illness length) and levels of anxiety
      and depression, predicted daytime fatigue severity, levels of daytime sleepiness
      and cognitive functioning, all key dimensions of the illness experience. METHODS:
      118 adults meeting the 1994 CDC case criteria for CFS completed a standardised
      sleep diary over 14 days. Momentary functional assessments of fatigue,
      sleepiness, cognition and mood were completed by patients as part of usual care.
      Levels of daytime functioning and disability were quantified using symptom
      assessment tools, measuring fatigue (Chalder Fatigue Scale), sleepiness (Epworth
      Sleepiness Scale), cognitive functioning (Trail Making Test, Cognitive Failures
      Questionnaire), and mood (Hospital Anxiety and Depression Scale). RESULTS:
      Hierarchical Regressions demonstrated that a shorter time since diagnosis, higher
      depression and longer wake time after sleep onset predicted 23.4% of the variance
      in fatigue severity (p <.001). Being male, higher depression and more afternoon
      naps predicted 25.6% of the variance in objective cognitive dysfunction (p
      <.001). Higher anxiety and depression and morning napping predicted 32.2% of the
      variance in subjective cognitive dysfunction (p <.001). When patients were
      classified into groups of mild and moderate sleepiness, those with longer daytime
      naps, those who mainly napped in the afternoon, and those with higher levels of
      anxiety, were more likely to be in the moderately sleepy group. CONCLUSIONS:
      Napping, particularly in the afternoon is associated with poorer cognitive
      functioning and more daytime sleepiness in CFS. These findings have clinical
      implications for symptom management strategies.

PMID- 25575049
TI  - [CCL21 promotes the metastasis of human pancreatic cancer Panc-1 cells via
      epithelial- mesenchymal transition].
AB  - OBJECTIVE: To investigate the mechanism underlying that chemokine (C-C motif)
      ligand 21 (CCL21) promotes the metastasis ability of human pancreatic cancer Panc
      1 cells. METHODS: Transwell(TM) was used to access the chemotaxis effect of CCL21
      on Panc-1 cells. Real-time quantitative PCR was performed to detect the
      expression of C-C chemokine receptor type 7 (CCR7) mRNA in the upper and lower
      chambers. Immunofluorescence staining and Western blotting were employed to
      examine the expressions of the epithelial-mesenchymal transition (EMT)-related
      proteins and CD133 of Panc-1 cells in the lower chamber, which were compared with
      those of the upper chamber as the control. RESULTS: The numbers of the Panc-1
      cells induced by 0, 50, 100, 200 ng/mL CCL21 were 13.00 +/- 3.00, 78.00 +/- 9.00,
      161.00 +/- 11.00, 281.00 +/- 17.00, respectively; with the increase of the
      concentration of CCL21, there were more cells migrating from the upper to the
      lower chamber; and the cells in the lower chamber expressed higher level of CCR7
      mRNA than the ones staying in the upper chamber. The relative protein expressions
      of MMP-9, vimentin, E-cadherin and CD133 in the lower chamber were 0.42 +/- 0.04,
      0.36 +/- 0.03, 0.12 +/- 0.02, 0.46 +/- 0.03, respectively, which were
      statistically significantly different from those in the upper chamber (0.15 +/-
      0.02, 0.25 +/- 0.02, 0.25 +/- 0.03, 0.13 +/- 0.02, respectively). CONCLUSION:
      CCL21/CCR7 axis maybe play an important role in the metastasis of pancreatic
      cancer stem cells by EMT and up-regulation of MMP-9.

PMID- 25575048
TI  - [The protective effect of augmenter of liver regeneration on mice with acute
      liver injury by up-regulating the expression levels of regulatory T cells].
AB  - OBJECTIVE: To study the protective effect and mechanism of augmenter of liver
      regeneration (ALR) on mice with acute liver injury. METHODS: Thirty BALB/c mice
      were randomly divided into normal control group, acute liver injury group and ALR
      intervention group. Acute liver injury group was given intraperitoneal injection
      of the mixture (2 mL/kg body mass once) of CCl4 (500 mL/L) and mineral oil. ALR
      intervention group was given ALR plasmid by tail intravenous injection 8 hours
      before CCl4 injection. The control group was injected the same amount of normal
      saline. The pathological changes of liver tissue were detected by HE staining.
      The serum was collected for detecting alanine transaminase (ALT) and aspartate
      transaminase (AST). The frequency of regulatory T cells (Tregs) in liver tissue
      was analyzed by flow cytometry. The mRNA levels of Foxp3, ALR, interleukin-6 (IL
      6) and tumor necrosis factor alpha (TNF-alpha) were measured by real-time
      quantitative PCR (qRT-PCR). RESULTS: The expression level of ALR mRNA in ALR
      intervention group was significantly higher than that in acute liver injury group
      and in normal control group; no statistically significant difference was found
      between the latter two groups. The frequency of Tregs in liver tissue had
      significant differences among these groups; CD25+Foxp3+Treg/CD4+T level was
      higher in ALR intervention group [(5.90 +/- 0.10)%] than in acute liver injury
      group [(4.23 +/- 0.46)%] and in normal control group [(2.93 +/- 0.74)%]; and it
      was higher in acute liver injury group than in normal control group. The
      expression level of Foxp3 mRNA in liver tissue had the same trend as the results
      of flow cytometry. It was higher in ALR intervention group than in acute liver
      injury group and in the normal control group. The mRNA levels of IL-6 and TNF
      alpha in ALR intervention group decreased as compared with acute liver injury
      group; the mRNA levels of IL-6 and TNF-alpha in acute liver injury group
      significantly increased as compared with the control group. CONCLUSION: ALR can
      protect mice against acute liver injury by up-regulating the expression of Tregs,
      which may be related to Tregs-mediated down-regulation of inflammatory cytokines
      IL-6 and TNF-alpha.

PMID- 25575050
TI  - [Inhibition of sunitinib on the expressions of PD-L1 and PD-L2 of mouse bone
      marrow-derived dendritic cells].
AB  - OBJECTIVE: To observe the changes of programmed death-1 ligand 1 (PD-L1) and PD
      L2 expressions on mouse bone marrow-derived dendritic cells (DCs) stimulated by
      sunitinib. METHODS: DCs were randomly divided into four groups which were treated
      with sunitinib (100, 200, 300 ng/mL) and dimethylsulfoxide (DMSO), respectively.
      After 48 hours, PD-L1 and PD-L2 expression levels were analyzed by flow
      cytometry. RESULTS: Compared with the control group, the expression of PD-L1 on
      mature DCs (mDCs) and all DCs [including mature DCs and immature DCs (imDCs)] was
      significantly down-regulated in sunitinib treatment groups. The PD-L1 expression
      percentages of imDCs, mDCs and DCs were significantly reduced in sunitinib
      treatment groups; the percentage of mDCs expressing PD-L2 also dropped in all
      treatment groups, and the percentage of DCs expressing PD-L2 decreased in 100 and
      300 ng/mL sunitinib treatment groups. CONCLUSION: Sunitinib can significantly
      reduce the expressions of PD-L1 and PD-L2 on mouse DCs.

PMID- 25575051
TI  - [Prediction and evolution of B cell epitopes of hemagglutinin in human-infecting
      H6N1 avian influenza virus].
AB  - OBJECTIVE: To predict B cell epitopes of hemagglutinin (HA) of human-infecting
      H6N1 avian influenza virus and analyze their evolutionary characteristics.
      METHODS: The dataset was downloaded from GISAID and GenBank databases. And the
      linear and conformational B cell epitopes of HA were predicted separately by
      various bioinformatic software. Furthermore, the conservation, adaptation and
      other evolutionary characteristics were also analyzed by some bioinformatic
      means. RESULTS: Four linear epitopes (A, B, C and D) and two conformational
      epitopes (E and F) were obtained after consideration of multiple factors. And the
      C epitope and sites ( 41, 157, 186, 187) mutated easily, but the other epitopes
      were very conservative and the D epitope was the most conservative.
      Interestingly, the site 157 was identified under positive selection, suggesting
      that it may be a particularly important site to make the virus evade the attack
      from the host immune system. CONCLUSION: The HA of human-infecting H6N1 avian
      influenza virus has five conservative B cell epitopes (three linear and two
      conformational) and one site under positive selection. The findings would
      facilitate the vaccine development, virus control and pathogenesis understanding.

PMID- 25575052
TI  - [Lentiviral vector-mediated Nanog short-hairpin RNA inhibits the growth of human
      gastric carcinoma xenograft in nude mice].
AB  - OBJECTIVE: To construct lentiviral vector that interferes with Nanog, investigate
      its expression in human gastric cancer cell SGC-7901-transplanted nude mice, and
      explore the effect of shRNA-Nanog transfection on the growth of the xenograft in
      mice. METHODS: Lentivirus carrying shRNA-Nanog was prepared by incorporating
      previously validated siRNA into Nanog gene specific lentiviral vectors. The
      models of human gastric cancer transplantation were constructed in nude mice. The
      mouse models were randomly divided into lentivirus-shRNA-Nanog transfection group
      (experimental group), GFP infection group (empty vector group) and uninfected
      group (control group). The tumor volume and mass changes were measured. Small
      animal in vivo imaging was employed to examine the fluorescent intensity and
      tumor metastasis. The Nanog protein expression was determined by Western blot
      analysis. The apoptosis of transinfected tumor cells was analyzed by TUNEL
      method. Results The gene sequencing demonstrated that the recombinant lentivirus
      carrying shRNA-Nanog was successfully established. In vivo imaging showed that 27
      days after transfection, the total fluorescent intensity in the experimental
      group was significantly lower than that in the empty vector group or the
      uninfected group. The xenograft volume and mass in the experimental group
      decreased significantly as compared with those in the empty vector group or the
      uninfected group. Western blotting indicated that the expression of Nanog protein
      in the experimental group was significantly lower than that in the empty vector
      or uninfected group. TUNEL results revealed that the apoptosis rate in the
      experimental group was significantly higher than that in the other two groups. No
      statistically significant difference was found between the empty vector group and
      the uninfected group. CONCLUSION: We successfully established Nanog gene-shRNA
      expression vector and capsulated it as lentivirus particles, which could inhibit
      the growth of xenograft in nude mice.

PMID- 25575053
TI  - [Silencing of carcinoembryonic antigen-related cell adhesion molecule 1 inhibits
      proliferation and induces apoptosis in human glioma SHG44 cells].
AB  - OBJECTIVE: To investigate the effect of siRNA-induced silencing of
      carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) on
      proliferation and apoptosis in human glioma SHG44 cells. METHODS: Three pairs of
      specific siRNA targeting CEACAM1 were designed and synthesized, and then
      transiently transfected into SHG44 cells via cationic liposome transfection
      method. Transfection efficiency was examined by flow cytometry (FCM). Real-time
      quantitative PCR (qRT-PCR) and Western blotting were respectively used to detect
      CEACAM1 expression at mRNA and protein levels, and the proliferation ability and
      apoptosis of SHG44 cells after transfection were assessed by CCK-8 assay and FCM
      in combination with annexin V-FITC/PI staining, respectively. The expression
      levels of cleaved caspase-3 and cleaved poly(ADP-ribose)polymerase (PARP)
      proteins were detected by Western blotting. RESULTS: The efficiency of CEACAM1
      siRNA transfection into human SHG44 cells were 85%. Forty-eight hours after the
      three pairs of specific CEACAM1 siRNA were transfected into SHG44 cells, qRT-PCR
      and Western blot results showed that the expression of CEACAM1 mRNA and protein
      were significantly inhibited compared with those in the blank control and the
      negative control groups, and the most significant interference effect was CEACAM1
      siRNA3. The proliferation of SHG44 cells was inhibited and the apoptosis rate was
      raised by the CEACAM1-siRNA transfection. The expression levels of cleaved
      caspase-3 and cleaved PARP proteins were up-regulated after silencing of CEACAM1.
      CONCLUSION: The siRNA-mediated CEACAM1 silencing can inhibit the proliferation
      and promote the apoptosis in human glioma SHG44 cells. CEACAM1 gene may be used
      as a potential therapeutic target of glioma.

PMID- 25575054
TI  - [Oxidative stress promotes hepatocyte apoptosis mediated by glycogen synthase
      kinase 3beta].
AB  - OBJECTIVE: To analyze the role of glycogen synthase kinase 3beta (GSK3beta) in
      hepatocyte apoptosis induced by oxidative stress. METHODS: Human HL-7702 hepatoma
      cells were induced by H2O2/antimycin A to establish oxidative stress-induced cell
      apoptosis models. SB216763, a specific inhibitor of GSK3beta, was given to the
      cells two hours before H2O2/antimycin A induction. Cell survival was observed
      using calcein acetoxymethyl ester/propidium iodide (PI) double staining, and cell
      apoptosis was detected using annexin V-FITC/PI staining combined with flow
      cytometry. In the meanwhile, the cell culture supernatant was subjected to
      lactate dehydrogenase (LDH) assay to evaluate the extent of cell death. The
      expressions of p-GSK3beta, GSK3beta, caspase-3, cleaved caspase-3, c-Jun N
      terminal kinase (JNK) and cytochrome C (CytC) proteins were examined using
      Western blotting. RESULTS: Oxidative stress triggered by H2O2/antimycin A
      promoted GSK3beta activity; inhibition of GSK3beta activity by SB216763 relieved
      oxidative stress and reduced cell apoptosis induced by oxidative stress. Compared
      with the model groups, SB216763 intervened group showed that the cell apoptosis
      rate and the level of LDH were reduced significantly, and that the expressions of
      cleaved caspase-3, JNK, CytC proteins decreased. CONCLUSION: GSK3beta is an
      important signaling molecule in the apoptosis pathway induced by oxidative
      stress. The inhibition on GSK3beta may alleviate the oxidative stress-induced
      hepatocyte apoptosis.

PMID- 25575055
TI  - [Leptin promotes the proliferation of airway smooth muscle cells and the
      expressions of HIF-1alpha and NF-kappaB of hypoxic rats].
AB  - OBJECTIVE: To investigate the effect of leptin on the proliferation of airway
      smooth muscle cells (ASMCs) and the expressions of hypoxia-inducible factor
      1alpha (HIF-1alpha) and nuclear factor-kappa B (NF-kappaB) of hypoxic rats.
      METHODS: The rat ASMCs were cultured under normoxic and hypoxic states. The
      hypoxic cells were divided into hypoxia group, leptin 50 MUg/L hypoxia group (L50
      group), leptin 100 MUg/L hypoxia group (L100 group), leptin 200 MUg/L hypoxia
      group (L200 group), leptin 200 MUg/L and leptin receptor antibody hypoxia group
      (ob-R antibody group) by random number table. All the groups are cultured for 24
      hours. Then the CCK-8 method was used to assay cell proliferation rate, and
      Western blotting and real-time RT-PCR to measure the expressions of HIF-1alpha
      and NF-kappaB at protein and mRNA levels. RESULTS: Compared with the normoxic
      group, each hypoxia group had significantly increased cell proliferation .
      Compared with the hypoxia group, cell proliferation rate was significantly raised
      in L50, L100 and L200 groups, and it was positively correlated with the
      concentration (r=0.992). Compared with L50, L100 and L200 groups, the ob-R
      antibody group showed significantly decreased cell proliferation rate. Compared
      with the normoxic group, each hypoxic group has increased expressions of HIF
      1alpha and NF-kappaB mRNA and proteins; compared with the hypoxia group, the
      expressions were significantly elevated in the L50, L100 and L200 groups and
      showed a positive correlation with the concentration; but the expressions were
      reduced in the ob-R antibody group as compared with L50, L100 and L200 groups.
      CONCLUSION: Leptin can promote rat ASMCs proliferation and the expressions of HIF
      1alpha and NF-kappaB under hypoxic condition.

PMID- 25575056
TI  - [Inhibition of S1PR2 activity down-regulates expressions of sphingosine kinase 1
      and MCP-1 in rat glomerular mesangial cells under high glucose].
AB  - OBJECTIVE: To investigate the effects of high glucose and the specific antagonist
      JTE-013 of sphingosine-1-phosphate receptor 2 (S1PR2) on the expressions of
      sphingosine kinase 1 (Sphk1), S1PR2 and monocyte chemoattractant protein-1 (MCP
      1) in rat glomerular mesangial cells. METHODS: The cultured rat GMCs were divided
      into four groups: normal glucose control group (NG, with 5.5 mmol/L glucose),
      mannitol group (HM, with 5.5 mmol/L glucose and 24.5 mmol/L mannitol), high
      glucose group (HG, with 30 mmol/L glucose), JTE-013 group (HJ, with 30 mmol/L
      glucose and 10 MUmol/L JTE-013). The mRNA levels of SphK1, S1PR2 and MCP-1 were
      determined with real-time quantitative PCR in the cells at 0, 12, 24 and 48
      hours, respectively, and the protein expression of MCP-1 in the supernatant was
      determined with ELISA . RESULTS: Compared with those in normal glucose, the mRNAs
      of SphK1 and S1PR2 in rat GMCs under high glucose were down-regulated at 12 hours
      and were then up-regulated as time went on, and peaked at 48 hours. High glucose
      significantly enhanced the mRNA expression of MCP-1 at 12 hours, and the
      expression reached the highest levels at 24 hours, but decreased at 48 hours. The
      protein expression of MCP-1 in rat GMCs time-dependently increased under high
      glucose compared with that in NG. After GMCs were treated with 10 MUmol/L JTE-013
      before exposed to high glucose for 24 hours, the mRNA levels of SphK1, S1PR2 and
      MCP-1 and the protein expression of MCP-1 significantly decreased compared with
      those in HG. CONCLUSION: Inhibition of S1PR2 activity could down-regulate the
      expressions of SphK1 and MCP-1 in rat GMCs under high glucose.

PMID- 25575057
TI  - [miR-25 promotes cell proliferation by targeting RECK in human cervical carcinoma
      HeLa cells].
AB  - OBJECTIVE: To investigate the effect of miR-25 on the proliferation of human
      cervical carcinoma HeLa cells and its association with reversion-inducing
      cysteine-rich protein with Kazal motifs (RECK). METHODS: The recombinant plasmids
      of pcDNATM6.2-GW-pre-miR-25, pmirGLO-RECK-WT, pmirGLO-RECK-MT and anti-miR-25
      were constructed, and their transfection efficiencies into HeLa cells were
      identified by real-time quantitative PCR (qRT-PCR). The potential proliferation
      stimulating function of miR-25 was analyzed by MTT assay in HeLa cells.
      Furthermore, the target effect of miR-25 on the RECK was determined by dual
      luciferase reporter assay system, qRT-PCR and Western blotting. RESULTS: Sequence
      analysis demonstrated that the recombinant plasmids of pcDNATM6.2-GW-pre-miR-25
      and pmirGLO-RECK-WT, pmirGLO-RECK-MT were successfully constructed, and qRT-PCR
      revealed that the transfection efficiencies of pre-miR-25 and anti-miR-25 were
      desirable in HeLa cells. MTT assay showed that miR-25 over-expression promoted
      the proliferation of HeLa cells. In addition, the luciferase activity was
      significantly reduced in HeLa cells cotransfected with pre-miR-25 and RECK-WT.
      The qRT-PCR and Western blotting indicated that the expression level of RECK was
      up-regulated in HeLa cells transfected with anti-miR-25 at the transcriptional
      and posttranscriptional levels. CONCLUSION: miR-25 could promote cell
      proliferation by targeting RECK in HeLa cells.

PMID- 25575058
TI  - [Activation of Wnt/beta-catenin pathway in NK cells by glycogen synthase kinase
      3beta inhibitor TWS119 promotes the expression of CD62L].
AB  - OBJECTIVE: To investigate the effect of Wnt/beta-catenin pathway activation by
      glycogen synthase kinase-3beta inhibitor 4,6-disubstituted pyrrolopyrimidine
      (TWS119) on proliferation and phenotypic characteristics of human nature killer
      (NK) cells. METHODS: The peripheral blood mononuclear cells (PBMCs) were obtained
      from healthy volunteers and added to the complete medium containing recombinant
      human interleukin-2 (rhIL-2) and human AB serum to isolate NK cells from PBMCs.
      After co-cultured with 0-8.0 MUmol/L TWS119 for 72 hours, growth curve and
      Wnt/beta-catenin activation of NK cells in each group were determined by CCK-8
      and Western blotting. The CD107a and CD62L (L-selectin) expressions in the NK
      cells were detected using flow cytometry. RESULTS: NK cells were amplified to
      (61.76 +/- 3.74)% after human PBMCs were cultured for 10 days. The 0-2.0 MUmol/L
      TWS119 could promote the growth of NK cells in a dose-dependent manner, and the
      proliferation rate gradually dropped when TWS119 was more than 2.0 MUmol/L. 0-8.0
      MUmol/L TWS119 could activate Wnt/beta-catenin pathway and up-regulate the
      expression of CD62L in a dose-dependent manner, but it decreased the expression
      of CD107a. CONCLUSION: Human NK cells isolated from peripheral blood treated with
      TWS119 gave rise to early mature CD62L+ NK cells.

PMID- 25575059
TI  - [Preparation of TAT-Ag85B protein vaccine and evaluation of its anti-Myobacterium
      tuberculosis effect].
AB  - OBJECTIVE: To obtain a new Ag85B protein fused with protein transduction domain
      (PTD) produced by a HIV-trans-activating transduction domain (TAT-PTD) expression
      system and investigate its protective effect against Myobacterium tuberculosis as
      a subunit vaccine. METHODS: The pET28a-Ag85B and pET28a-TAT-Ag85B plasmids were
      established and transformed into E.coli BL21(DE3) strains for recombinant protein
      expression and purification. Then three groups of BALB/c mice were subcutaneously
      vaccinated three times with Ag85B protein, TAT-Ag85B protein and PBS,
      respectively. One week after the last immunization, 5 mice in each group were
      sacrificed for detecting serum specific anti-Ag85B and IFN-gamma/IL-2 produced by
      spleen cells using ELISA. Simultaneously, the levels of CD80 and CD86 on
      macrophages which were stimulated by Ag85B or TAT-Ag85B protein were measured
      using flow cytometry. Subsequently, the rest of the mice were intravenously
      injected with virulent Myobacterium tuberculosis H37Rv and their bacterial loads
      in the lung and spleen were determined 1, 2, 4 and 8 weeks after infection.
      Moreover, pulmonary pathological changes were observed by HE staining at 8 weeks
      after infection. RESULTS: Ag85B and TAT-Ag85B proteins were obtained
      successfully. Compared with Ag85B, higher titers of IgG antibodies and the levels
      of IFN-gamma and IL-2 were induced by TAT-Ag85B. Lower bacterial loads in the
      lung and spleen and smaller scale of pulmonary lesion were found in mice
      immunized with TAT-Ag85B than those in Ag85B-treated mice. In addition, TAT-Ag85B
      stimulated higher CD80 and CD86 expressions on macrophages. CONCLUSION: TAT-Ag85B
      protein is an efficient vaccine that induces a strong Th1 immune response and
      provides a good protection against Myobacterium tuberculosis infection. The
      mechanism of the subunit vaccine may be partially explained as the enhanced
      capability of antigen-presentation of macrophages.

PMID- 25575060
TI  - [Isolation and culture of fetal bovine intestine-derived epithelial stem cells
      and the differentiation into hepatocyte-like cells].
AB  - OBJECTIVE: To establish the culture system of fetal bovine intestinal epithelial
      stem cells (IESCs) in vitro, identify specific markers of the cell lines and
      analyze the differentiation potential into hepatocyte-like cells. METHODS: IESCs
      were isolated from the 3- to 5-month fetal bovine intestine by the digestion of
      collagenase I, and cultured in the DMEM/F12 medium. The cell morphology was
      observed, and the proliferation ability and multiple differentiation potential
      were demonstrated by subculturing and its growth curve. The mRNA expressions of
      the surface markers Bmi1, Hes1, Lgr5 and cytokeratin 19 (CK19) were determined by
      reverse transcription PCR (RT-PCR), and the protein levels of Bmi1, LGR5 and CK19
      were detected by immunofluorescence cytochemistry. Under the induction of
      fibroblast growth factor 4 (FGF-4) and hepatocyte growth factor (HGF), the cell
      differentiation into hepatocyte-like cells was assayed by the glycogen staining
      and RT-PCR. RESULTS: IESCs cultured in vitro expressed Bmi1, Hes1, Lgr5 and CK19
      mRNAs, and CK19, Bmi1 and LGR5 proteins. The differentiated cells were positively
      stained by glycogen, and RT-PCR showed that the cells expressed alpha-fetoprotein
      (AFP) and albumin (ALB) mRNAs. CONCLUSION: The culture system of IESCs in vitro
      is successfully established, and the cells are differentiated into hepatocyte
      like cells.

PMID- 25575061
TI  - [Therapeutic efficacy of dendritic cells pulsed by autologous tumor cell lysate
      in combination with CIK cells on advanced renal cell carcinoma].
AB  - OBJECTIVE: To investigate the clinical efficacy of dendritic cells (DCs)
      sensitization by autologous tumor cell lysate in combination with cytokine
      induced killer (CIK) cells on patients with advanced renal cell carcinoma and
      detect their immune functions and adverse effects. METHODS: The study analyzed
      retrospectively 82 patients with advanced renal cell carcinoma admitted in our
      department from January 2011 to December 2013. Peripheral blood mononuclear cells
      (PBMCs) were isolated from the above patients. Adherent cells were cultured to
      produce DCs. The DCs were pulsed with autologous tumor cell lysate (Ag) to
      produce Ag-DC. T lymphocytes were cultured to prepare CIK. The Ag-DC was co
      cultured with CIK to produce Ag-DC-CIK vaccine, and then the phenotypes of the
      DCs and the secretion of IL-12 were evaluated. CIK cell proliferation was
      determined, too. The 41 patients received the immunotherapy of Ag-DC-CIK, and the
      other 41 patients received CIK cell therapy alone. After 2 cycles of treatment,
      the changes of T cell subtypes and cytokines released in the peripheral blood
      were evaluated. The therapeutic outcomes were evaluated with the help of
      imageology. The adverse effects were also observed. RESULTS: Compared with the
      DCs alone, DCs pulsed with autologous tumor cell lysates expressed significantly
      surface molecules CD11c, CD83, CD86 and HLA-DR, and the release of IL-12
      significantly increased. CIK cell proliferation was significantly enhanced after
      co-cultured with the Ag-DC. Meanwhile, the percentages of CD3+CD8+ cells and
      CD3+CD56+ cells went up significantly compared with the controls. Clinical
      responses of the Ag-DC-CIK treatment group were much better than those of the
      control group. No severe adverse effects were seen in the two groups. CONCLUSION:
      DCs derived from PBMCs of advanced renal cell carcinoma patients harboring the
      autologous tumor cell antigens can differentiate into mature DCs, which
      facilitate the proliferation of CIK cells. Ag-DC-CIK vaccine improves the immune
      status of patients with advanced renal cell carcinoma.

PMID- 25575063
TI  - [HBV infection in placental Hofbauer cells and the association with the level of
      HBV replication].
AB  - OBJECTIVE: To study the clinical significance of Hofbauer cells of maternal
      placenta in hepatitis B virus (HBV) vertical infection. METHODS: Hofbauer cells
      were isolated and purified from human placental villi by the methods of enzyme
      digestion, mechanical method and Ficoll-Hypaque separation. The Hofbauer cells
      were identified by anti-CD163 immunohistochemistry and the level of HBV-DNA in
      Hofbauer cells was detected by PCR. The expressions of CD16 (FcgammaRIII) mRNA
      and protein in Hofbauer cells were measured by real-time quantitative PCR (qRT
      PCR) and immunohistochemistry, respectively. RESULTS: The positive detection rate
      of HBV-DNA in Hofbauer cells of HBV-infected pregnant women was 31.67% (19/60),
      and among them, the HBeAg+ and HBeAg- were 46.4% (13/28) and 18.75% (6/32),
      respectively. The expressions of CD16 mRNA and protein in Hofbauer cells of
      patients with HBV-DNA were significantly higher than those in patients without
      HBV-DNA, and had an obvious correlation with the rate of HBV-DNA. CONCLUSION:
      Hofbauer cells as placental macrophages can be infected by HBV, and the infection
      rate is associated with the level of viral replication in vivo.

PMID- 25575062
TI  - [Th2 differentiation features of Mycobacterium tuberculosis heat resistant
      antigen-activated human gammadeltaT cells and the regulation of transcription
      factor T-bet/GATA-3 on differentiation].
AB  - OBJECTIVE: To investigate Th2 differentiation features of Mycobacterium
      tuberculosis heat resistant antigens (MTB-HAg)-activated human gammadeltaT cells
      and the regulation of transcription factor T-box expression in T cells (T-bet)
      and GATA-binding protein 3 (GATA-3) on differentiation. METHODS: Peripheral blood
      mononuclear cells (PBMCs) were stimulated with MTB-HAg to generate MTB-HAg
      activated T cells (MTBAT) and expanded in the neutral condition or Th2 polarizing
      condition. After restimulation for 6 hours with phorbol myristate acetate (PMA,
      10 ng/mL), ionomycin (500 ng/mL) and monensin (2.5 MUmol/L), intracellular
      cytokines (IFN-gamma, IL-4) of gammadeltaT cells and alphabetaT cells among MTBAT
      were detected by four-color fluorescence mAb staining combined with flow
      cytometry. The highly purified gammadeltaT cells and CD4+ T cells were sorted by
      flow cytometer from MTBAT that were cultured in neutral and Th2 polarizing
      conditions for 28 days. The expressions of T-bet and GATA-3 mRNA in purified
      gammadeltaT cells and CD4+ T cells were determined by reverse transcription PCR
      (RT-PCR) technique. RESULTS: gammadeltaT cells among MTBAT cultured in the
      neutral or Th2 polarizing condition predominantly produced IFN-gamma, whereas the
      percentage of IFN-gamma+ alphabetaT cells significantly decreased in the Th2
      polarizing condition as the culture time went by. Compared with the neutral
      condition, Th0 type (IFN-gamma+ IL-4+) gammadeltaT cells significantly increased,
      and Th2 type (IFN-gamma- IL-4+) alphabetaT cells also significantly increased in
      the Th2 polarizing condition. RT-PCR showed that mRNA expression of T-bet was
      still at a high level in gammadeltaT cells that were expanded in the Th2
      polarizing condition, but at a low level in Th2 polarized CD4+ T cells. Moreover,
      the mRNA expressions of GATA-3 in both Th2 polarized gammadeltaT cells and CD4+T
      cells were up-regulated. CONCLUSION: In the Th2 polarizing condition, the
      majority of gammadeltaT cells in MTBAT still remained Th1 profile, whereas the
      portion of gammadeltaT cells differentiated into Th0 type cells. Both
      transcription factor T-bet and GATA-3 failed to display a fully cross-regulation
      function in Th2 polarized gammadeltaT cells.

PMID- 25575064
TI  - [Elevated levels of Th17/regulatory T cells in peripheral blood are associated
      with disease activity of patients with rheumatoid arthritis].
AB  - OBJECTIVE: To detect the relative quantity of Th17 cells and regulatory T cell
      (Tregs) in peripheral blood of patients with rheumatoid arthritis (RA) and
      explore its clinical significance. METHODS: The study enrolled 60 patients who
      met the diagnostic criteria of RA and 15 healthy subjects as control group. Using
      flow cytometry, we tested the percentage of Th17 cells/Tregs in the total CD4+
      cells in peripheral blood and contrasted the difference between the RA patients
      and healthy subjects. Then we analyzed the relationships of the Th17 cells/Tregs
      expression with the numbers of swollen and tender joints, DAS28 scores, pain
      intensity on a visual analogue scale (VAS), erythrocyte sedimentation rate (ESR)
      and C-reactive protein (CRP). RESULTS: Compared with the controls, the RA
      patients presented with significantly increased Th17 cell number and decreased
      Tregs. There was a positive correlation between the number of Th17 cells in
      peripheral blood of the RA patients and the numbers of swollen and tender joints,
      DAS28 scores and CRP, and no correlation between the number of Tregs and the
      indices of the disease activity like the numbers of swollen and tender joints,
      DAS28 scores, pain on the VAS, ESR and CRP. CONCLUSION: The relative quantity of
      Th17 cells rises and that of Tregs drops in peripheral blood of RA patients, and
      the increase of Th17 cells is related to the disease activity of RA.

PMID- 25575065
TI  - [Correlation analysis between killer cell immunoglobulin-like receptor gene
      polymorphism and primary biliary cirrhosis].
AB  - OBJECTIVE: To explore the association between killer cell immunoglobulin-like
      receptor (KIR) gene polymorphism and primary biliary cirrhosis (PBC) in Jiangsu
      Han population. METHODS: Peripheral blood samples were taken from 122 patients
      with PBC hospitalized in third people's hospital of Changzhou in Jiangsu province
      between June 2011 and July 2013 and 198 randomly matched unrelated healthy
      donors. KIR was typed by SYBR(R)Green I real-time PCR genotyping assay. Gene and
      genotype frequencies of KIR were compared between the two groups. RESULTS: The
      gene frequencies of KIR2DL2 and 2DS2 were significantly lower in the PBC group as
      compared with those of the control group. KIR2DL2 and 2DS2 were associated with
      lower risk of PBC. The total 55 KIR genotypes were found in the patients (24
      genotypes) and the controls (47 genotypes). The most commonly observed KIR
      genotype was AA1 , and the next were BX2, BX8, BX4 and BX14 . Only 11 genotypes
      were observed in five individuals or more, allowing for a meaningful comparison
      of genotype frequencies between the patients and controls. There was no
      statistically significant difference in genotype frequencies between the two
      groups. CONCLUSION: The absence of KIR2DL2/2DS2 genotype may be associated with
      protection against PBC in Jiangsu Han population.

PMID- 25575066
TI  - [IL-35 level of peripheral blood is correlated with the immune response to
      hepatitis B vaccine].
AB  - OBJECTIVE: To investigate the relationship of IL-35 level in peripheral blood
      mononuclear cells (PBMCs) and immune response to hepatitis B vaccine and explore
      the factors influencing vaccine immune reaction. METHODS: Our follow-up study
      enrolled 400 healthy volunteers who had received a standard course of
      immunization with hepatitis B vaccine. Chemiluminescence method was carried out
      to quantitatively detect hepatitis B virus surface antibody (HBsAb). PBMCs were
      isolated from 8 cases of non- or hypo-responders and 8 cases of moderate or hyper
      responders, and the total RNA was extracted. Real-time quantitative PCR was
      performed to detect Epstein-Barr virus (EBV)-induced gene 3 (EBI3) and IL-12p35
      mRNA levels. Finally, serum IL-35 level was compared using ELISA between 40 cases
      of non- or hypo-responders and 40 cases of moderate or hyper-responders randomly
      selected from the healthy volunteers to analyze the association with HBsAb level.
      RESULTS: The levels of EBI3 and IL-12p35 mRNAs in PBMCs in moderate or hyper
      responders were significantly higher than those in non- or hypo-responders, and
      the former was (12.73 +/- 2.26) and (7.93 +/- 1.06) folds the latter,
      respectively. The serum IL-35 level in moderate or hyper-responders [(111.50 +/-
      49.53) ng/L] was significantly higher than that in non-or hypo-responders [(15.01
      +/- 12.82) ng/L]; and IL-35 level was positively correlated with HBsAb level
      (r=0.84). CONCLUSION: Peripheral blood IL-35 level was closely correlated with
      the immune response to hepatitis B vaccine and low IL-35 level might be one of
      possible reasons or mechanisms underlying non-response or hypo-response to
      hepatitis B vaccine immunization.

PMID- 25575067
TI  - [Xinfeng Capsule increases peripheral blood BTLA expression of CD19(+) and
      CD24(+) B cells and relieves oxidative stress damage to improve cardiac function
      of patients with rheumatoid arthritis].
AB  - OBJECTIVE: To observe the changes in cardiac function, peripheral blood B and T
      lymphocyte attenuator (BTLA) and oxidative stress related indicators in
      rheumatoid arthritis(RA) patients, thus to explore the mechanism underlying the
      improving effect of Xinfeng Capsule (XFC) on cardiac function. METHODS: The study
      enrolled 100 RA patients and divided them randomly into 2 groups, XFC treatment
      group and leflunomide (LEF) control group (n=50 per group). The treatment lasted
      30 days for one course. Other 40 healthy people from Medical Examination Center
      were included as a normal control (NC) group. Flow cytometry was used to detect
      the expression and activation level of BTLA, Westergren method was used to
      determine erythrocyte sedimentation rate (ESR), and automatic biochemical
      analyzer to examine high sensitivity C-reactive protein (hs-CRP) and rheumatoid
      factor (RF). ELISA method was performed to observe related cytokines (IL-1beta,
      IL-17, IL-35, IFN-gamma) and markers of oxidative stress such as total
      antioxidant capacity (TAOC), malondialdehyde (MDA), reactive oxygen species
      (ROS), superoxide dismutase (SOD), glutathione (GSH). Echocardiography was
      utilized to survey cardiac function parameters including heart ejection fraction
      (EF%), stroke volume (SV%), fractional shortening (FS%), E peak velocities (E)
      and A peak velocities (A) of mitral valve flow, and the ratio of filling fraction
      of E and A (E/A). RESULTS: Compared with the NC group, EF%, E peak velocity, E/A
      were significantly reduced while A peak velocity increased in RA patients, and
      FS% was not found obviously different. In addition, IL-1beta, IL-17 and
      inflammatory indexes like ESR, CRP increased while BTLA, IL-35, IFN-gamma
      decreased significantly; Serum ROS, MDA rose and SOD, GSH dropped significantly
      in RA patients. Correlation analysis showed that the cardiac function parameters
      EF, FS were negatively correlated with CD24+ cells and CD19+CD24+ cells, that E/A
      was positively correlated with BTLA, that A peak velocity was positively related
      to CD19+ cells, that EF was positively related to ROS, that SV was positively
      related with MDA, SOD, that E peak velocity was negatively correlated with TAOC.
      After drug intervention, XFC treatment group got 86% total effective rate. XFC
      obviously improved cardiac function regarding EF%, FS%, E peak, E/A and other
      parameters, increased serum SOD, GSH capacity, eliminated ROS, MDA, increased
      BTLA, IL-35, IFN-gamma, and reduced IL-1beta, IL-17. Compared with LEF group, XFC
      had a better improving effect on DAS28 and cardiac function parameters.
      CONCLUSION: XFC can increase BTLA expression of CD19+ and CD24+ B cells and
      reduce B cell-mediated abnormal humoral immunity and oxidative stress damage,
      thus improving cardiac function and quality of life.

PMID- 25575068
TI  - [Preparation and identification of the polyclonal antibody against heat shock
      protein 70 (DnaK) from Shigella flexneri 5a M90T].
AB  - OBJECTIVE: To generate polyclonal antibodies against Shigella flexneri 5a M90T
      heat shock protein 70 (DnaK) and identify the specificity and titer of
      antibodies. METHODS: The sequence of Shigella flexneri 5a M90T dnaK gene was
      amplified by PCR and inserted into expression vector pET-24a to obtain
      recombinant plasmid pET24a-dnaK. Then the recombinant plasmid pET24a-dnaK was
      transformed into E.coli BL21 (DE3) and expressed under IPTG induction. The
      recombinant DnaK proteins with His-tag (DnaK-His) were then purified by affinity
      purification. The polyclonal antibodies were prepared by immunizing the mice with
      the purified recombinant proteins and then harvesting mouse sera. The specificity
      and titer of the polyclonal antibodies were identified by Western blotting, ELISA
      and immunofluorescent staining. RESULTS: The recombinant plasmid pET24a-dnaK was
      expressed efficiently in E.coli BL21 (DE3). The polyclonal antibodies harvested
      from the mice immunized with DnaK-His were demonstrated being specific to
      Shigella flexneri 5a M90T DnaK proteins, and could be efficient in Western
      blotting, ELISA and immunofluorescent staining. CONCLUSION: The polyclonal
      antibodies against Shigella flexneri 5a M90T DnaK protein have been successfully
      prepared.

PMID- 25575069
TI  - [Preparation and characterization of monoclonal antibodies against human CA50 and
      establishment of chemiluminescence immunoassay system].
AB  - OBJECTIVE: To prepare the anti-human carbohydrate antigen 50(CA50) monoclonal
      antibody (mAb), characterize its immunological features and establish a
      chemiluminescence immunoassay system with it. METHODS: BALB/c mice were immunized
      with human CA50 antigen for preparing mAb using hybridoma technique. Stable anti
      CA50-secreting hybridoma cell lines were obtained after screening. The mAbs were
      purified using protein A after expanding culture. The chemiluminescence
      immunoassay system was established and evaluated in its linear range, accuracy,
      sensitivity, reproducibility, and the blood samples were tested with it. RESULTS:
      Four hybridoma cell lines were obtained respectively and their titers were above
      1:10(8). Anti-CA50 mAbs nearly had no cross-reaction with CA125, CA153, CA199 and
      CA724. The linear detection of the chemiluminescence immunoassay system covered a
      range 0-500 U/mL. The recovery rate for accuracy was 107.08% and its sensitivity
      was 0.83 U/mL. The assay was highly repeatable [coefficient of variation
      (CV)<10%]. The correlation coefficient with the test of reference reagent was
      0.96. CONCLUSION: The monoclonal antibodies against human CA50 had been screened
      and a chemiluminescence immunoassay system for human CA50 detection had been
      established successfully.

PMID- 25575070
TI  - [Preparation and identification of the polyclonal antibody against extracellular
      domain (405T-573Q) of rat Toll-like receptor 2].
AB  - OBJECTIVE: To prepare the polyclonal antibody of the extracellular domain (405T
      573Q) of rat Toll-like receptor 2 (TLR2) and identify its activity. METHODS:
      Firstly, the extracellular domain (507 bp) of rat TLR2 was amplified from rat
      hepatocytes by reverse transcription PCR, and the recombinant plasmid pET28a
      TLR2ex was constructed. Secondly, the fusion protein TLR2ex-6*His was expressed
      in E.coli BL21(DE3) and purified by affinity chromatography. And then, the
      polyclonal antibody was prepared by immunizing the BALB/c mice with the purified
      fusion protein. Finally, the titer and specificity of the polyclonal antibody
      were analyzed by ELISA and Western blotting, respectively. RESULTS: The
      recombinant plasmid pET28a-TLR2ex was successfully constructed, and the TLR2ex
      6*His fusion protein was successfully expressed and purified. Western blotting
      demonstrated that the antibody from the TLR2ex-6*His-immunized BALB/c mice
      specifically and selectively bound with rat TLR2. ELISA also indicated that the
      titer of polyclonal antibody reached 1:76 800. CONCLUSION: The polyclonal
      antibody against the extracellular domain (405T-573Q) of rat TLR2 has been
      successfully prepared.

PMID- 25575071
TI  - Stroke after adult-onset epilepsy: a population-based retrospective cohort study.
AB  - BACKGROUND: Earlier studies indicate a higher risk of subsequent stroke in PWE
      aged >=60. However, little is known of the incidence of subsequent stroke in
      people with epilepsy (PWE) aged 35 through 60. We determined the risk factors
      that increase the incidence of stroke following adult-onset epilepsy in a large
      statewide population over a 10-year period. METHODS: South Carolina hospital
      discharge and emergency department (ED) data from 2000 to 2011 were used. The
      study was limited to persons aged >=35years without prior stroke. Cases included
      patients diagnosed with epilepsy who were hospitalized or visited the ED.
      Controls were people with an isolated fracture of the lower extremity without any
      history of epilepsy or seizure disorders, presumed to approximate the health
      status of the general population. Epilepsy, fracture, stroke, and comorbid
      conditions were ascertained by diagnostic codes from health-care encounters. Only
      persons having stroke occurring >=6months after the onset of epilepsy or after
      the first clinical encounter for controls were included. Cox proportional hazards
      modeling was performed to determine the risk of stroke. RESULTS: There were
      21,035 cases with epilepsy and 16,638 controls who met the inclusion criteria.
      Stroke incidence was 2.5 times higher following adult-onset epilepsy (6.3%)
      compared with controls (2.5%). After adjusting for comorbidities and other
      factors, cases with epilepsy showed a 60% higher risk of stroke (HR=1.6; 95% CI:
      1.42-1.80) compared with controls. Nearly half of the strokes in cases with
      epilepsy occurred in those with first diagnosis between ages 35 and 55. Somatic
      comorbidities associated with increased risk of stroke were more prevalent in
      cases with epilepsy than controls yet similar in both groups with stroke. Risk of
      stroke increased with increasing age in both groups. However, the risk of stroke
      in cases with epilepsy increased faster and was similar to that in controls who
      were >=10years older. CONCLUSION: Adult-onset epilepsy at age 35 and older
      warrants consideration for occult cerebrovascular disease as an etiology of the
      epilepsy, which may also increase the risk of subsequent stroke. Somatic
      comorbidities frequently associated with epilepsy include comorbid conditions
      that share the same underlying pathology with stroke (i.e., hypertension,
      hyperlipidemia, myocardial infarction, diabetes, and arteriosclerosis). This
      increased risk of stroke in patients with adult-onset epilepsy should dictate the
      evaluation and management of stroke risk factors to prevent stroke.

PMID- 25575072
TI  - Isomer-specific trophic transfer of perfluorocarboxylic acids in the marine food
      web of Liaodong Bay, North China.
AB  - Trophic transfers of perfluorocarboxylic acids (PFCAs) have been well studied in
      aquatic food webs; however, most studies examined PFCAs as single compounds
      without differentiating isomers. In this study, an in-port derivatization GC-MS
      method was used to determine PFCA (perfluorooctanoic acid, PFOA;
      perfluorononanoic acid, PFNA; perfluorodecanoate acid, PFDA; perfluoroundecanoate
      acid, PFUnDA; perfluorododecanoate acid, PFDoDA; perfluorotridecanoate acid,
      PFTriDA, and perfluorotetradecanoate acid, PFTeDA) structural isomers in 11
      marine species including benthic invertebrates, fishes, and gulls collected in
      November 2006 from Liaodong Bay in China. The total concentrations of linear
      PFCAs were 0.35-1.10, 0.93-2.61, and 2.13-2.69 ng/g ww, and the corresponding
      percentages of branched PFCAs to linear PFCAs were 6.6-15.5%, 4.2-9.9%, and 4.5
      6.0% in invertebrates, fishes, and birds, respectively. Except for linear PFOA,
      significant positive relationships were found between the concentrations of all
      the target linear PFCAs and trophic levels, and the trophic magnification factors
      (TMFs) ranged from 1.90 to 4.88. Positive correlations between the concentrations
      of branched PFCAs isomers and trophic levels were also observed but were without
      statistical significance. The relatively high biomagnification of linear isomers
      of PFCAs would lead to low percentages of branched PFCAs to total PFCAs in
      organisms at high trophic levels. This study for the first time clarified isomer
      specific trophic transfers of PFCAs in a marine food web.

PMID- 25575073
TI  - Unraveling the TWIST between EMT and cancer stemness.
AB  - Twist1 has a well-established role in inducing Epithelial-Mesenchymal Transition
      (EMT) to promote tumor invasion and metastasis and can also inhibit apoptosis and
      confer stemness. In this issue of Cell Stem Cell, Beck et al. (2015) now show
      that low levels of Twist1 are essential for tumor initiation, maintenance, and
      stemness independent of its EMT-inducing activity.

PMID- 25575074
TI  - Targeting the cellular origin of organ fibrosis.
AB  - Organ fibrosis after injury, which can significantly compromise tissue function,
      is in part due to proliferation of fibroblasts and myofibroblasts of unclear
      cellular origin. Now in Cell Stem Cell, Kramann et al. (2015) show that
      perivascular Gli1+ mesenchymal-stem-cell-like cells generate a large fraction of
      myofibroblasts in disease conditions.

PMID- 25575075
TI  - In search of human hematopoietic stem cell identity.
AB  - Better insight into hematopoietic stem cell (HSC) development in the human embryo
      and fetus is crucial for translational research. In this issue of Cell Stem Cell,
      Prashad et al. (2014) describe a novel surface marker for human fetal liver HSCs,
      glycosylphosphatidylinositol-anchored protein GPI-80, that is functionally
      required for their self-renewal.

PMID- 25575076
TI  - Waddington's valleys and Captain Cook's islands.
AB  - Somatic reprogramming has relied heavily on theoretical models that view
      differentiation in terms of developmental branch point decisions. Recent studies
      in Cell now reveal a dominant role of the microenvironment in shaping epigenetic
      identity of macrophages, thus providing support for alternative models of cell
      fate acquisition. 

PMID- 25575077
TI  - F-class cells: new routes and destinations for induced pluripotency.
AB  - A series of five related publications describe an alternative pluripotent state
      that is dependent on continuous high levels of exogenous reprogramming factor
      expression. A comprehensive effort to molecularly compare the acquisition of this
      state to induced pluripotency aims at providing new insights into the mechanisms
      underlying cellular reprogramming. 

PMID- 25575078
TI  - Clonal evolution in cancer: a tale of twisted twines.
AB  - Intra-tumor heterogeneity of cancer cells hampers the design of effective
      therapies and yet it is poorly reproduced in experimental models. A recent report
      by Eirew at al. provides an in-depth analysis of genetic heterogeneity of breast
      tumor xenografts and shows that changes in clonal diversity might not be
      stochastic. 

PMID- 25575079
TI  - Generating iPSCs: translating cell reprogramming science into scalable and robust
      biomanufacturing strategies.
AB  - Induced pluripotent stem cells (iPSCs) have the potential to transform drug
      discovery and healthcare in the 21(st) century. However, successful
      commercialization will require standardized manufacturing platforms. Here we
      highlight the need to define standardized practices for iPSC generation and
      processing and discuss current challenges to the robust manufacture of iPSC
      products. 

PMID- 25575080
TI  - Different levels of Twist1 regulate skin tumor initiation, stemness, and
      progression.
AB  - Twist1 promotes epithelial-to-mesenchymal transition (EMT), invasion, metastasis,
      and cancer stem cell (CSC) properties. However, it remains unclear whether Twist1
      is also required for tumor initiation and whether Twist1-induced cancer stemness
      and EMT are functionally linked. Using a conditional deletion of Twist1 at
      different stages of skin carcinogenesis, we show that Twist1 is required for skin
      tumor initiation and progression in a gene-dosage-dependent manner. Moreover,
      conditional ablation of Twist1 in benign tumors leads to increased apoptosis,
      reduced cell proliferation, and defective tumor maintenance and propagation
      independently of its EMT-inducing abilities. Concomitant deletion of Twist1 and
      p53 rescues the apoptotic response, but not the cell proliferation and
      propagation defects. These results reveal that Twist1 is required for tumor
      initiation and maintenance in a p53-dependent and -independent manner.
      Importantly, our findings also indicate that tumor stemness and EMT can be
      regulated by distinct mechanisms. 

PMID- 25575082
TI  - Membrane rigidity induced by grafted polymer brush.
AB  - The contribution of neutral polymer brush to the curvature elasticity of the
      grafting surface is investigated theoretically. Using self-consistent field
      theory, we accurately evaluate the dependence of bending modulus on parameters
      including chain length, Flory-Huggins parameter and grafting density and reveal
      the importance of solvent. The results show that the brush-induced bending
      modulus follows a complex dependence on grafting density and Flory-Huggins
      parameter, while it obeys a simple power law with chain length as N(3). The
      method is further applied to calculate the polymer brush's contribution to the
      elastic properties of PEG-grafted lipid monolayers. 

PMID- 25575083
TI  - Electrodeposition and bipolar effects in metallized nanopores and their use in
      the detection of insulin.
AB  - Solid-state nanopore devices with integrated electrodes are an important class of
      single-molecule biosensors, with potential applications in DNA, RNA, and protein
      detection and sequence analysis. Here we investigate solid-state nanopore sensors
      with an embedded gold film, fabricated using semiconductor processing techniques
      and focused ion beam milling. We characterize their geometric structure in three
      dimensions on the basis of experimental conductance studies and modeling as well
      as transmission electron microscopy imaging and tomography. We used
      electrodeposition to further shrink the pores to effective diameters below 10 nm
      and demonstrate how bipolar electrochemical coupling across the membrane can lead
      to significant contributions to the overall pore current and discuss its
      implications for nanopore sensing. Finally, we use metallized nanopores modified
      with homocysteine for the detection of insulin. We show that adsorption of the
      protein to the chemically modified nanopores slows down the translocation process
      to tens of milliseconds, which is orders of magnitude slower than expected for
      conventional electrophoretic transport. 

PMID- 25575081
TI  - Single-cell transcriptome analysis reveals dynamic changes in lncRNA expression
      during reprogramming.
AB  - Cellular reprogramming highlights the epigenetic plasticity of the somatic cell
      state. Long noncoding RNAs (lncRNAs) have emerging roles in epigenetic
      regulation, but their potential functions in reprogramming cell fate have been
      largely unexplored. We used single-cell RNA sequencing to characterize the
      expression patterns of over 16,000 genes, including 437 lncRNAs, during defined
      stages of reprogramming to pluripotency. Self-organizing maps (SOMs) were used as
      an intuitive way to structure and interrogate transcriptome data at the single
      cell level. Early molecular events during reprogramming involved the activation
      of Ras signaling pathways, along with hundreds of lncRNAs. Loss-of-function
      studies showed that activated lncRNAs can repress lineage-specific genes, while
      lncRNAs activated in multiple reprogramming cell types can regulate metabolic
      gene expression. Our findings demonstrate that reprogramming cells activate
      defined sets of functionally relevant lncRNAs and provide a resource to further
      investigate how dynamic changes in the transcriptome reprogram cell state. 

PMID- 25575084
TI  - Minimally invasive decompression versus x-stop in lumbar spinal stenosis: a
      randomized controlled multicenter study.
AB  - STUDY DESIGN: Prospective randomized controlled multicenter study. OBJECTIVE: To
      compare the effect of X-Stop with minimally invasive decompression (MID) in
      patients with neurogenic intermittent claudication due to lumbar spinal stenosis.
      SUMMARY OF BACKGROUND DATA: Lumbar spinal stenosis is the most common indication
      for operative treatment in elderly. Laminectomy has been the "gold standard," but
      MID is now widely used. Another minimally invasive surgery option is X-Stop
      showing good result compared with nonoperative treatment, but showing higher
      reoperation rate than laminectomy. METHODS: We enrolled 96 patients aged 50 to 85
      years, with symptoms of neurogenic intermittent claudication within 250-m walking
      distance and 1- or 2-level lumbar spinal stenosis, randomized to either MID or X
      Stop. Primary outcome was Zurich Claudication Questionnaire in this intention-to
      treat analysis. Secondary outcome was Oswestry Disability Index, EuroQol 5
      dimensional questionnaire, numerical rating scale 11 for lower back pain and leg
      pain, and risk for secondary surgery and complications. RESULTS: No significant
      differences were found in Zurich Claudication Questionnaire between the groups at
      any follow-ups. Both groups had a statistical and clinical significant
      improvement at 6 weeks and throughout the 2-year observation period. The number
      of patients having secondary surgery due to persistent or recurrent symptoms was
      significantly higher in the X-Stop group, odds ratio (95% confidence interval) =
      6.5 (1.3-31.9). Complication rate was similar and low, but more severe for MID.
      CONCLUSION: Both MID and X-Stop led to significant symptom improvements. There
      were no significant clinical differences in effect between the methods at any of
      the follow-up time points. X-Stop had significant higher risk of secondary
      surgery. Complication was more severe for MID.

PMID- 25575085
TI  - Monitoring the quality of robot-assisted pedicle screw fixation in the lumbar
      spine by using a cumulative summation test.
AB  - STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVE: The aim of this
      study was to monitor the quality control of robot-assisted pedicle screw fixation
      accuracy by using a cumulative summation (CUSUM) test at the initial stage of its
      application. SUMMARY OF BACKGROUND DATA: Although robot-assisted pedicle screw
      fixation reduces screw misplacement rates and provides critical support for
      minimally invasive surgical procedures, there have been no reports relating to
      the monitoring of quality control of the accuracy of this robot-assisted pedicle
      screw fixation procedure. METHODS: Patients with lumbar spinal stenosis scheduled
      to undergo surgery were randomly and equally assigned through 1:1 allocation to a
      robot-assisted minimally invasive posterior lumbar interbody fusion (Rom-PLIF)
      group or a conventional open posterior PLIF using freehand technique group. The
      accuracy of pedicle screw placement was evaluated using postoperative computed
      tomography. The primary outcome was the CUSUM analysis for monitoring the quality
      control of the accuracy of pedicle screw insertion between the Rom-PLIF and
      conventional open posterior PLIF using freehand technique groups. RESULTS: Of the
      80 pedicle screws inserted in each group, 4 screws in the Rom-PLIF group, and 7
      in the conventional open PLIF group, breached the pedicle. Of these 11 offending
      screws, 4 cases were categorized as grade B in the Rom-PLIF group, whereas 6 were
      grade B and 1 case was grade C in the Com-PLIF group, using the Gertzbein and
      Robbins classification. Throughout the monitoring period, there was no CUSUM test
      derived indication that the quality of performance of the pedicle screw fixation
      procedure was inadequate in either group. CONCLUSION: First, this study
      demonstrates the adequacy of quality control of robot-assisted pedicle screw
      fixation even early in the application period based on the CUSUM analysis.
      Second, the CUSUM test can be a useful tool for monitoring of the quality of
      procedures related with spine surgery.

PMID- 25575086
TI  - Validation of an administrative coding algorithm for classifying surgical
      indication and operative features of spine surgery.
AB  - STUDY DESIGN: Retrospective review of medical records and administrative data.
      OBJECTIVE: Validate a claims-based algorithm for classifying surgical indication
      and operative features in lumbar surgery. SUMMARY OF BACKGROUND DATA:
      Administrative data are valuable to study rates, safety, outcomes, and costs in
      spine surgery. Previous research evaluates outcomes by procedure, not indications
      and operative features. One previous study validated a coding algorithm for
      classifying surgical indication. Few studies examined claims data for classifying
      patients by operative features. METHODS: Patients undergoing lumbar decompression
      or fusion at a single institution in 2009 for back pain, herniated disc,
      stenosis, spondylolisthesis, or scoliosis were included. Sensitivity and
      specificity of a claims-based algorithm for indication and operative features
      were examined versus medical record abstraction. RESULTS: A total of 477
      patients, including 246 (52%) undergoing fusion and 231 (48%) undergoing
      decompression were included in this study. Sensitivity of the claims-based coding
      algorithm for classifying the indication for the procedure was 71.9% for
      degenerative disc disease, 81.9% for disc herniation, 32.7% for spinal stenosis,
      90.4% for degenerative spondylolisthesis, and 93.8% for scoliosis. Specificity
      was 87.9% for degenerative disc, 85.6% for disc herniation, 90.7% for spinal
      stenosis, 95.0% for degenerative spondylolisthesis, and 97.3% for scoliosis.
      Sensitivity and specificity of claims data for identifying the type of procedure
      for fusion cases was 97.6% and 99.1%, respectively. Sensitivity of claims data
      for characterizing key operative features was 81.7%, 96.4%, and 53.0% for use of
      instrumentation, combined (anterior and posterior) surgical approach, and 3 or
      more disc levels fused, respectively. Specificity was 57.1% for instrumentation,
      94.5% for combined approaches, and 71.9% for 3 or more disc levels fused.
      CONCLUSION: Claims data accurately reflected certain diagnoses and type of
      procedures, but were less accurate at characterizing operative features other
      than the surgical approach. This study highlights both the potential and current
      limitations of claims-based analysis for spine surgery.

PMID- 25575087
TI  - Discectomy-related information on the internet: does the quality follow the
      surge?
AB  - STUDY DESIGN: A quality-control Internet-based study using recognized quality
      scoring systems. OBJECTIVE: To evaluate the quality of information available on
      the Internet. SUMMARY OF BACKGROUND DATA: Quality of health information on the
      Internet is of much concern and the emphasis for appraisal of Internet Web sites
      is needed. This study is to determine if it has improved with the surge in
      Internet usage. METHODS: The 3 most commonly used search engines were identified
      and a search for "Discectomy" was performed on each. Two reviewers categorized
      the Web sites according to their types and the quality of each was assessed using
      recognized scoring systems including the Journal of the American Medical
      Association (JAMA) benchmark, DISCERN score, and discectomy-specific content
      score. The quality of the information was also assessed according to the presence
      and absence of the Health on the Net code. RESULTS: Fifty-three Web sites were
      identified, and analyzed. Commercial Web sites were predominant, 24 of them were
      identified, 7 were governmental, 6 were produced by physicians, none were
      produced by allied health professionals, 3 were academic, 4 were public health
      information Web sites, 4 were attached to social media and discussion groups, 3
      were related to media, and 2 were unspecified. Internet sites with a Health on
      the Net code demonstrated significantly higher quality than those without the
      code (P < 0.0001). Public health information Web sites attained the highest
      overall DISCERN and discectomy-specific scores followed by Web sites of the
      government and nonprofit organizations. CONCLUSION: The overall quality of
      information regarding discectomy remains poor and variable despite an exponential
      increase in the number of users and Web sites, with a slight trend toward
      improvement, only 20% to 30% are of good quality, compared with that 10 years ago
      (<10%). Presence of Health on the Net code is a very reliable marker for health
      information quality.

PMID- 25575088
TI  - A pioneering patient lift: prevention of low back pain in health care workers in
      the 18th century.

PMID- 25575089
TI  - Hyperextension injuries of the thoracolumbar spine in diffuse idiopathic skeletal
      hyperostosis.
AB  - STUDY DESIGN: Retrospective study of a consecutive series of patients with
      thoracolumbar hyperextension injuries (TLHIs) complicated by diffuse idiopathic
      skeletal hyperostosis (DISH) presenting to a single institution during a 9-year
      period. OBJECTIVE: Assess epidemiological data, trauma mechanism, injury
      characteristics in hyperostotic spines, and short-term outcome. SUMMARY OF
      BACKGROUND DATA: An increase in TLHIs complicated by DISH was observed. In
      current literature, only case reports and small case series touch this topic.
      METHODS: All patients with TLHIs in the setting of DISH between January 2002 and
      December 2010 were reviewed retrospectively. Clinical and radiographical data
      during hospitalization including computed tomographic scans of all patients were
      analyzed as to epidemiological issues, trauma characteristics, neurological
      deficits, and short-term outcomes. Statistical analysis was performed to assess
      factors related to trauma characteristics. RESULTS: Twenty patients with 23 TLHIs
      were analyzed. Twelve injuries involved the thoracic region; 1, the lumbar
      region; and 10, the thoracolumbar junction. A total of 85.7% of injuries were due
      to high-energy impact. The distribution of transdiscal and transosseous injuries
      was almost equal (13/10). Patients with DISH with vertebral body fractures were
      significantly older than those with transdiscal injuries (78.3 yr vs. 69.8 yr, P
      < 0.026). Post-traumatic neurological deficit was present in 22.7% patients.
      Neurological complications did not occur in low-energy injuries. On average,
      spines were posteriorly stabilized over 2.1 segments. Twenty percent of the
      patients died within 3 months (average age, 80.7 +/- 5.1 yr, range, 76-88 yr).
      CONCLUSION: To our knowledge, this is the largest series of TLHIs in DISH-altered
      spines in literature. The study helps to understand controversial findings in
      literature about morphological properties of TLHIs in DISH-affected spines.
      Surgeons should be aware of preexisting alterations in traumatized spines and the
      impact on therapeutic decisions. Because of the "aging population" and
      implications of metabolic diseases on an "aging spine," the incidence of TLHIs in
      DISH will probably rise.

PMID- 25575090
TI  - Cultural adaptation, reliability, and validity of neck disability index in Indian
      rural population: a Marathi version study.
AB  - STUDY DESIGN: A cross-sectional study to develop a cultural adaptation of the
      Marathi-neck disability index (NDI) and to investigate its validity and
      reliability. OBJECTIVE: To conduct a study concerning the cultural adaptation of
      the NDI and investigate the validity and reliability of its Marathi version in
      patients with neck pain. SUMMARY OF BACKGROUND DATA: The NDI is a reliable
      instrument for evaluating self-rated disability due to neck pain, but there is no
      published Marathi version and also it has not been tested on a rural population
      yet. Successful linguistic and cultural translation may allow appropriate cross
      cultural comparison for clinical and laboratory research analysis, even in the
      rural parts of the Maharashtra state of India, where English is not the language
      of communication. METHODS: Eighty-one patients having neck pain for at least 3
      months were included in the study. The NDI and visual analogue scale for pain
      were completed by all subjects. Test-retest reliability was determined by using
      intraclass correlation coefficient and Pearson correlation analysis. For the
      determination of construct validity, the relation between the NDI and visual
      analogue scale was examined by Pearson correlation analysis. RESULTS: Intraclass
      correlation coefficient score for test-retest reliability was 0.95 and the
      Cronbach alpha was 0.97. For construct-related validity the correlation of the
      NDI-Marathi version was found to be 0.95 (P < 0.0001). These results showed that
      the construct validity of the Marathi version of the NDI was excellent.
      CONCLUSION: The results suggest that the Marathi version of the NDI that is
      validated in this study is an easy to comprehend, reliable, and valid instrument
      for the measurement for the limitation of activities of daily living and pain
      caused by neck disorders in the Marathi-speaking population.

PMID- 25575091
TI  - Cross-cultural adaptation and validation of the neck disability index to European
      Portuguese language.
AB  - STUDY DESIGN: Cross-cultural adaptation and psychometric testing. OBJECTIVE: To
      complete the cultural adaptation of the European Portuguese version of the neck
      disability index (NDI-PT) and to investigate its reliability and validity in
      patients with chronic neck pain (CNP). SUMMARY OF BACKGROUND DATA: The NDI is the
      most widely used instrument for self-reporting of disability due to neck pain.
      Although the NDI has demonstrated both good reliability and validity, a recent
      systematic review called attention for the poor methodological quality of the
      translation processes and psychometric studies. METHODS: The NDI-PT was first
      piloted in a sample of 40 patients with CNP. Then, 113 patients with CNP
      completed the numeric pain rating scale and twice the NPI-PT with an interval of
      4 to 7 days. Factor structure of the NDI was explored through principal component
      factor analysis. The internal consistency was estimated using the Cronbach alpha
      coefficient. Reliability was determined by repeatability using intraclass
      correlation coefficient (2,1) for the total sample and for the subsample of
      participants who remained stable in CNP status between the initial and follow-up
      assessment based upon the global rating of change scale, and agreement using the
      concept of "limits of agreement." Construct validity was assessed with
      correlations between the NDI-PT and the numeric pain rating scale for convergent
      validity, using Pearson correlation analysis. RESULTS: Exploratory factor
      analysis revealed the existence of 1 major factor that explained 54.7% of the
      variance. Test-retest reliability was 0.9 and internal consistency was 0.95. No
      systematic trend was observed in the Bland and Altman method. The NDI-PT showed a
      good correlation with pain intensity (r = 0.525, P < 0.01). CONCLUSION: The NDI
      PT demonstrated excellent reliability and good construct validity and it may be
      useful for assessing functional status of Portuguese-speaking patients with CNP.

PMID- 25575092
TI  - The Oswestry Disability Index (version 2.1a): validation of a Dutch language
      version.
AB  - STUDY DESIGN: A cross-sectional study on baseline data. OBJECTIVE: To translate
      the Oswestry Disability Index (ODI) version 2.1a into the Dutch language and to
      validate its use in a cohort of patients with chronic low back pain in secondary
      spine care. SUMMARY OF BACKGROUND DATA: Patient-reported outcome measures (PROMs)
      are commonly accepted to evaluate the outcome of spine interventions. Functional
      status is an important outcome in spine research. The ODI is a recommended
      condition-specific patient-reported outcome measure used to evaluate functional
      status in patients with back pain. As yet, no formal translated Dutch version
      exists. METHODS: The ODI was translated according to established guidelines. The
      final version was built into the electronic web-based system in addition with the
      Roland Morris Disability Questionnaire, the numeric rating scale for pain
      severity, 36-Item Short Form Health Survey Questionnaire for quality of life, and
      the hospital anxiety and depression scale. Baseline data were used of 244
      patients with chronic low back pain who participated in a combined physical and
      psychological program. Floor and ceiling effects, internal consistency, and the
      construct validity were evaluated using quality criteria. RESULTS: The mean ODI
      (standard deviation) was 39.6 (12.3); minimum 6, maximum 70. Most of the
      participants (88%) were moderately to severely disabled. Factor analysis
      determined a 1-factor structure (36% explained variance) and the homogeneity of
      ODI items is shown (Cronbach alpha = 0.79). The construct validity is supported
      as all (6:6) the a priori hypotheses were confirmed. Moreover, the ODI and Roland
      Morris Disability Questionnaire, showed a strong significant correlation (r =
      0.68, P < 0.001) and an overlap: mean difference of -18 (95% limits of agreement:
      -44 to 8). CONCLUSION: The Dutch ODI version 2.1a is a valid and valuable tool
      for the measurement of functional status and disability among Dutch patients with
      chronic low back pain. This translated condition-specific patient-reported
      outcome measure version is recommended for use in future back pain research and
      to evaluate outcome of back care in the Netherlands.

PMID- 25575093
TI  - Towards the development of an outcome instrument for spinal trauma: an
      international survey of spinal surgeons.
AB  - STUDY DESIGN: International web-based survey. OBJECTIVE: To identify the most
      relevant aspects of human function and health status from the perspective of
      health care professionals involved in the treatment of spinal trauma patients.
      SUMMARY OF BACKGROUND DATA: There is no universally accepted outcome instrument
      available that is specifically designed or validated for spinal trauma patients,
      contributing to controversies related to the optimal treatment and evaluation of
      many types of spinal injuries. Therefore, the AOSpine Knowledge Forum Trauma aims
      to develop such an instrument using the International Classification of
      Functioning, Disability, and Health (ICF) as its basis. METHODS: Experts from the
      5 AOSpine International world regions were asked to give their opinion on the
      relevance of a compilation of 143 ICF categories for spinal trauma patients on a
      3-point scale: "not relevant," "probably relevant," or "definitely relevant." The
      responses were analyzed using frequency analysis. Possible differences in
      responses between the 5 world regions were analyzed with the Fisher exact test
      and descriptive statistics. RESULTS: Of the 895 invited AOSpine International
      members, 150 (16.8%) participated in this study. A total of 13 (9.1%) ICF
      categories were identified as definitely relevant by more than 80% of the
      participants. Most of these categories were related to the ICF component
      "activities and participation" (n = 8), followed by "body functions" (n = 4), and
      "body structures" (n = 1). Only some minor regional differences were observed in
      the pattern of answers. CONCLUSION: More than 80% of an international group of
      health care professionals experienced in the clinical care of adult spinal trauma
      patients indicated 13 of 143 ICF categories as definitely relevant to measure
      outcomes after spinal trauma. This study creates an evidence base to define a
      core set of ICF categories for outcome measurement in adult spinal trauma
      patients.

PMID- 25575094
TI  - Measuring lumbar reposition accuracy in patients with unspecific low back pain:
      systematic review and meta-analysis.
AB  - STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To evaluate if
      patients with nonspecific chronic low back pain (NSCLBP) show a greater lumbar
      reposition error (RE) than healthy controls. SUMMARY OF BACKGROUND DATA: Studies
      on lumbar RE in patients with NSCLBP present conflicting results. METHODS: A
      systematic review and meta-analysis of the available literature were performed to
      evaluate differences in RE between patients with NSCLBP and healthy controls.
      Data on absolute error, constant error (CE), and variable error were extracted
      and effect sizes (ESs) were calculated. For the CE flexion pattern and active
      extension pattern, subgroups of patients with NSCLBP were analyzed. Results of
      homogeneous studies were pooled. Measurement protocols and study outcomes were
      compared. The quality of reporting and the authors' appraisal of risk of bias
      were investigated. RESULTS: The original search revealed 178 records of which 13
      fulfilled the inclusion criteria. The majority of studies showed that patients
      with NSCLBP produced a significantly larger absolute error (ES, 0.81; 95%
      confidence interval [95% CI], 0.13-1.49) and variable error (ES, 0.57; 95% CI,
      0.05-1.09) compared with controls. CE is direction specific in flexion and active
      extension pattern subgroups of patients with NSCLBP (ES, 0.39; 95% CI, -1.09 to
      0.3) and ES, 0.18; 95% CI, -0.3 to 0.65, respectively). The quality of reporting
      and the authors' appraisal of risk of bias varied considerably. The applied test
      procedures and instrumentation varied between the studies, which hampered the
      comparability of studies. CONCLUSION: Although patients with NSCLBP seemed to
      produce a larger lumbar RE compared with healthy controls, study limitations
      render firm conclusions unsafe. Future studies should pay closer attention to
      power, precision, and reliability of the measurement approach, definition of
      outcome measures, and patient selection. We recommend a large, well-powered,
      prospective randomized control study that uses a standardized measurement
      approach and definitions for absolute error, CE, and variable error to address
      the hypothesis that proprioception may be impaired with CLBP.

PMID- 25575096
TI  - Bifunctional sensing characteristics of chemical vapor deposition synthesized
      atomic-layered MoS2.
AB  - Two-dimensional (2D) molybdenum disulfide (MoS2) atomic layers have a strong
      potential to be adopted for 2D electronic components due to extraordinary and
      novel properties not available in their bulk foams. Unique properties of the
      MoS2, including quasi-2D crystallinity, ultrahigh surface-to-volume, and a high
      absorption coefficient, have enabled high-performance sensor applications.
      However, implementation of only a single-functional sensor presents a limitation
      for various advanced multifunctional sensor applications within a single device.
      Here, we demonstrate the charge-transfer-based sensitive (detection of 120 ppb of
      NO2) and selective gas-sensing capability of the chemical vapor deposition
      synthesized MoS2 and good photosensing characteristics, including moderate
      photoresponsivity (~71 mA/W), reliable photoresponse, and rapid photoswitching
      (<500 ms). A bifunctional sensor within a single MoS2 device to detect photons
      and gas molecules in sequence is finally demonstrated, paving a way toward a
      versatile sensing platform for a futuristic multifunctional sensor. 

PMID- 25575098
TI  - Identification in Rat Plasma and Urine by Linear Trap Quadrupole-Orbitrap Mass
      Spectrometry of the Metabolites of Maslinic Acid, a Triterpene from Olives.
AB  - Maslinic acid is a natural pentacyclic triterpenoid widely distributed in edible
      and medicinal plants with health-promoting activities. The identification and
      quantification of its metabolites is a requirement for a better understanding of
      the biological effects of this triterpene. Therefore, maslinic acid was orally
      administered to Sprague-Dawley rats at a dose of 50 mg/kg of body weight. Blood
      and urine were withdrawn at 45 min. Samples were extracted with ethyl acetate
      prior to liquid chromatography-atmospheric pressure chemical ionization-linear
      trap quadrupole-Orbitrap (LC-APCI-LTQ-Orbitrap) analysis. Screening of plasma
      yielded four monohydroxylated derivatives (M1-M4), one monohydroxylated and
      dehydrogenated metabolite (M5), and two dihydroxylated and dehydrogenated
      compounds (M6 and M7). In urine, M1, M4, M5, and M6 were detected. Quantification
      by LC-APCI-mass spectrometry (MS) revealed maslinic acid as the prevalent
      compound in both plasma (81.8%) and urine (73.9%), which indicates that
      metabolism is low and mainly attributable to phase I reactions.

PMID- 25575097
TI  - Socioeconomic differentials in smoking duration among adult male smokers in
      China: result from the 2006 China Health and Nutrition Survey.
AB  - BACKGROUND: A smoker's risk of diseases and death from smoking is closely related
      to his/her smoking duration. But little is known about the average length of
      smoking and the association between smoking duration and socio-economic status
      (SES) among Chinese smokers. METHODS: A sample of male ever smokers (N = 2,637)
      aged 18+ years was drawn from the 2006 China Health and Nutrition Survey to
      examine the average length of smoking and socioeconomic differentials in smoking
      duration. Kaplan-Meier analysis was used to obtain median smoking duration. Log
      logistic regression models were employed to estimate the relative duration of
      smoking, adjusted for demographic characteristics, smoking history, and health
      status. RESULTS: Results showed that Chinese male ever smokers aged 18 years and
      older had a median duration of smoking of 58 years (95% CI: 56-61). Male ever
      smokers with a lower status job (i.e. farmers, manual and skilled workers,
      service workers, and office staff) had a significantly longer duration of smoking
      than those with a professional or administrative job after adjusted for
      demographic characteristics, smoking history, and health status. Individuals who
      earned the lowest income and who had no education or were being illiterate smoked
      for 11% and 14% longer, respectively, relative to those who had the highest
      income or who had college or above education. CONCLUSION: The findings
      demonstrated the problem of long smoking duration and a pattern of social
      disparities in smoking duration among Chinese male smokers. Social disparities in
      smoking behavior may exacerbate the already existing social inequalities in
      health. Thus, policies and interventions to promote smoking cessation should pay
      more attention to disadvantaged social groups.

PMID- 25575095
TI  - Evaluation overview for the Massachusetts Childhood Obesity Research
      Demonstration (MA-CORD) project.
AB  - BACKGROUND: The Massachusetts Childhood Obesity Research Demonstration (MA-CORD)
      project is a 2-year, multilevel, multisector community intervention to prevent
      and control obesity among children 2-12 years of age from two predominantly low
      income communities in Massachusetts. MA-CORD includes evidence-based
      interventions in multiple sectors, including community health centers, early care
      and education centers, schools, afterschool programs, the Special Supplemental
      Nutrition Program for Women, Infants and Children, and the broader community.
      Currently, implementation of MA-CORD is complete and the final year of data
      collection is in progress. Here, the MA-CORD evaluation plan is described and
      baseline data are presented. METHODS/DESIGN: The impact of MA-CORD on children's
      BMI, lifestyle behaviors, obesity-related care, and quality of life will be
      assessed using sector-specific, pre/post, time-series, and quasi-experimental
      designs. Change in the primary outcomes will be compared for intervention and
      comparison communities. Additionally, change in mean BMI and obesity prevalence
      in intervention school districts will be compared to similar districts throughout
      the state. RESULTS: At baseline in 2012, approximately 16% of preschool-aged and
      25% of school-aged children were obese. Moreover, 15-40% of children consumed no
      vegetables on the previous day, 25-75% drank a sugar-sweetened beverage on the
      previous day, up to 87% had insufficient physical activity, 50-75% had a
      television in the room where they slept, and 50-80% obtained insufficient sleep.
      CONCLUSIONS: There is ample room for improvement in BMI and health behaviors in
      children in MA-CORD communities. If successful, MA-CORD may serve as a model for
      multilevel, multisector approaches to childhood obesity prevention and control.

PMID- 25575100
TI  - Characterization of 3D joint space morphology using an electrostatic model (with
      application to osteoarthritis).
AB  - Joint space morphology can be indicative of the risk, presence, progression,
      and/or treatment response of disease or trauma. We describe a novel methodology
      of characterizing joint space morphology in high-resolution 3D images (e.g. cone
      beam CT (CBCT)) using a model based on elementary electrostatics that overcomes a
      variety of basic limitations of existing 2D and 3D methods. The method models
      each surface of a joint as a conductor at fixed electrostatic potential and
      characterizes the intra-articular space in terms of the electric field lines
      resulting from the solution of Gauss' Law and the Laplace equation. As a test
      case, the method was applied to discrimination of healthy and osteoarthritic
      subjects (N = 39) in 3D images of the knee acquired on an extremity CBCT system.
      The method demonstrated improved diagnostic performance (area under the receiver
      operating characteristic curve, AUC > 0.98) compared to simpler methods of
      quantitative measurement and qualitative image-based assessment by three expert
      musculoskeletal radiologists (AUC = 0.87, p-value = 0.007). The method is
      applicable to simple (e.g. the knee or elbow) or multi-axial joints (e.g. the
      wrist or ankle) and may provide a useful means of quantitatively assessing a
      variety of joint pathologies.

PMID- 25575104
TI  - Esophageal stricture due to magnesium citrate powder ingestion: a unique case.

PMID- 25575099
TI  - Membranoproliferative glomerulonephritis due to visceral leishmaniasis in an HIV
      patient.
AB  - BACKGROUND: Visceral leishmaniasis is an important opportunistic disease in HIV
      positive patients. The information available on the effects of such co-infection
      in the kidney is limited. We describe a patient with HIV/leishmania coinfection
      who developed nephrotic syndrome and membranoproliferative glomerulonephritis. As
      far as we know, only 2 cases of this nephropathy in HIV/leishmania coinfection
      have been reported. CASE REPORT: A 47-year-old man developed nephrotic syndrome.
      He had been diagnosed with HIV infection and visceral leishmaniasis and was
      treated with antiretroviral therapy, antimonial compounds, liposomal amphotericin
      B and miltefosine, but the leishmania followed a relapsing course. Renal biopsy
      disclosed membranoproliferative glomerulonephritis and leishmania amastigotes
      were seen within glomerular capillary lumens. He was given miltefosine and
      liposomal amphotericin B but the leishmaniasis persisted. Stage 3B chronic renal
      disease and nephrotic range proteinuria tend to become stable by 15-month follow
      up. CONCLUSIONS: Our case illustrated some aspects of leishmaniasis in HIV
      patients: its relapsing course, the difficulties in therapy, and the renal
      involvement.

PMID- 25575105
TI  - Abernethy malformation: congenital absence of the portal vein.

PMID- 25575106
TI  - Serrated adenoma prevalence in inflammatory bowel disease surveillance
      colonoscopy, and characteristics revealed by chromoendoscopy and virtual
      chromoendoscopy.
AB  - BACKGROUND: Sessile or nonpolypoid neoplastic lesions, including sessile serrated
      adenomas (SSAs), are difficult to detect in patients with inflammatory bowel
      disease (IBD). OBJECTIVES: To assess the prevalence and endoscopic features of
      SSA in IBD patients undergoing surveillance colonoscopy using novel endoscopic
      techniques. METHODS: Histology results of biopsies from a cohort of 87 patients
      (47 men; median age 51.4 years; median duration of disease 16.9 years; ulcerative
      colitis [n=40], Crohn disease [n=43], ischemic colitis [n=4]) with longstanding
      colonic IBD undergoing surveillance colonoscopy were reviewed. Lesions of
      dysplasia (adenoma-like mass, or dysplasia-associated lesion or mass), SSAs,
      adenoma-like polyps, hyperplastic polyps and inflammatory polyps were identified.
      Surveillance colonoscopy using high-definition alone, or with iScan (Pentax, USA)
      dye-sprayed or virtual chromoendoscopy was performed. Lesion characteristics were
      described before histological diagnosis. RESULTS: Fourteen SSAs were detected in
      87 (11%) IBD patients. The endoscopic characteristics of SSA lesions were:
      nonpolypoid appearance (86%), predominant localization in the proximal colon
      (79%), >6 mm in size (79%), cloudy cover (64%), Kudo pit pattern modified type
      IIO (86%) and irregular spiral vascular pattern (79%). Among the 44 SSAs and
      hyperplastic polyps found in the present study, the above characteristics of SSA
      at colonoscopy had a sensitivity of 92.86% (95% CI 66.06% to 98.8%) and
      specificity of 93.33% (95% CI 77.89% to 98.99%) in predicting a histological
      diagnosis of SSA (positive predictive value 86.67%, negative predictive value
      96.55%). CONCLUSION: SSAs are a common finding at surveillance colonoscopy in IBD
      and have several characteristic features. Further studies are needed to evaluate
      the natural history of these lesions in IBD patients.

PMID- 25575107
TI  - Rates of minor adverse events and health resource utilization postcolonoscopy.
AB  - BACKGROUND: Little is known about minor adverse events (MAEs) following
      outpatient colonoscopies and associated health care resource utilization.
      OBJECTIVE: To estimate the rates of incident MAE at two, 14 and 30 days
      postcolonoscopy, and associated health care resource utilization. A secondary aim
      was to identify factors associated with cumulative 30-day MAE incidence. METHODS:
      A longitudinal cohort study was conducted among individuals undergoing an
      outpatient colonoscopy at the Montreal General Hospital (Montreal, Quebec).
      Before colonoscopy, consecutive individuals were enrolled and interviewed to
      obtain data regarding age, sex, comorbidities, use of
      antiplatelets/anticoagulants and previous symptoms. Endoscopy reports were
      reviewed for intracolonoscopy procedures (biopsy, polypectomy). Telephone or
      Internet follow-up was used to obtain data regarding MAEs (abdominal pain,
      bloating, diarrhea, constipation, nausea, vomiting, blood in the stools, rectal
      or anal pain, headaches, other) and health resource use (visits to emergency
      department, primary care doctor, gastroenterologist; consults with nurse,
      pharmacist or telephone hotline). Rates of incident MAEs and health resources
      utilization were estimated using Bayesian hierarchical modelling to account for
      patient clustering within physician practices. RESULTS: Of the 705 individuals
      approached, 420 (59.6%) were enrolled. Incident MAE rates at the two-, 14- and 30
      day follow-ups were 17.3% (95% credible interval [CrI] 8.1% to 30%), 10.5% (95%
      CrI 2.9% to 23.7%) and 3.2% (95% CrI 0.01% to 19.8%), respectively. The 30-day
      rate of health resources utilization was 1.7%, with 0.95% of participants seeking
      the services of a physician. No predictors of the cumulative 30-day incidence of
      MAEs were identified. DISCUSSION: The incidence of MAEs was highest in the 48 h
      following colonoscopy and uncommon after two weeks, supporting the Canadian
      Association of Gastroenterology's recommendation for assessment of late
      complications at 14 days. Predictors of new onset of MAEs were not identified,
      but wide CrIs did not rule out possible associations. Although <1% of
      participants reported consulting a physician for MAEs, this figure may represent
      a substantial number of visits given the increasing number of colonoscopies
      performed annually. CONCLUSION: Postcolonoscopy MAEs are common, occur mainly in
      the first two weeks postcolonoscopy and result in little use of health resources.

PMID- 25575108
TI  - Predictors of mortality among patients undergoing colectomy for ischemic colitis:
      A population-based United States study.
AB  - BACKGROUND: Ischemic colitis is a potentially life-threatening condition that can
      require colectomy for management. OBJECTIVE: To assess independent predictors of
      mortality following colectomy for ischemic colitis using a nationally
      representative sample of hospitals in the United States. METHODS: The Nationwide
      Inpatient Sample was used to identify all patients with a primary diagnosis of
      acute vascular insufficiency of the colon (International Classification of
      Diseases, Ninth Revision codes 557.0 and 557.9) who underwent a colectomy between
      1993 and 2008. Incidence and mortality are described; multivariate logistic
      regression analysis was performed to determine predictors of mortality. RESULTS:
      The incidence of colectomy for ischemic colitis was 1.43 cases (95% CI 1.40 cases
      to 1.47 cases) per 100,000. The incidence of colectomy for ischemic colitis
      increased by 3.1% per year (95% CI 2.3% to 3.9%) from 1993 to 2003, and
      stabilized thereafter. The postoperative mortality rate was 21.0% (95% CI 20.2%
      to 21.8%). After 1997, the mortality rate significantly decreased at an estimated
      annual rate of 4.5% (95% CI -6.3% to -2.7%). Mortality was associated with older
      age, 65 to 84 years (OR 5.45 [95% CI 2.91 to 10.22]) versus 18 to 34 years;
      health insurance, Medicaid (OR 1.69 [95% CI 1.29 to 2.21]) and Medicare (OR 1.33
      [95% CI 1.12 to 1.58]) versus private health insurance; and comorbidities such as
      liver disease (OR 3.54 [95% CI 2.79 to 4.50]). Patients who underwent colonoscopy
      or sigmoidoscopy (OR 0.78 [95% CI 0.65 to 0.93]) had lower mortality.
      CONCLUSIONS: Colectomy for ischemic colitis was associated with considerable
      mortality. The explanation for the stable incidence and decreasing mortality
      rates observed in the latter part of the present study should be explored in
      future studies.

PMID- 25575109
TI  - Too many authors spoil the credit.

PMID- 25575110
TI  - Minor adverse events postcolonoscopy.

PMID- 25575112
TI  - The hidden realities of endoscopy unit budgeting.

PMID- 25575113
TI  - How to explain recent multiple reports on the decline of inflammatory bowel
      disease in Canada.

PMID- 25575111
TI  - Biomarkers in nonalcoholic fatty liver disease.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition
      characterized by insulin resistance, type 2 diabetes and fat accumulation in the
      liver that may cause hepatic inflammation and progressive scarring leading to
      nonalcoholic steatohepatitis (NASH) and irreversible liver damage (cirrhosis). As
      a result, there has been increased recognition of the need to assess and closely
      monitor individuals for risk factors of components of NAFLD and NASH, as well as
      the severity of these conditions using biomarkers. AIM: To review the biomarkers
      used to diagnose and define the severity of NAFLD and NASH. METHODS: A
      comprehensive PubMed and Google Scholar literature search was performed using the
      terms "non-alcoholic fatty liver disease", "non-alcoholic steatohepatitis", as
      well as the name of each biomarker known to be used. Articles indexed between
      2004 and 2014 were used. Each author read the publications separately and the
      results were discussed. RESULTS: Biomarkers offer a potential prognostic or
      diagnostic indicator for disease manifestation, progression or both. Serum
      biomarkers, including total cholesterol, triglycerides, insulin resistance and C
      peptide, have been used for many years. Emerging biomarkers, such as
      apolipoprotein A1, apolipoprotein B, leptin, adiponectin, free fatty acids,
      ghrelin and tumour necrosis factor-alpha, have been proposed as tools that could
      provide valuable complementary information to that obtained from traditional
      biomarkers. Moreover, markers of cell death and mitochondrial dysfunction
      (cytokeratins) represent powerful predictors of risk. For biomarkers to be
      clinically useful in accurately diagnosing and treating disorders, age-specific
      reference intervals that account for differences in sex and ethnic origin are a
      necessity. CONCLUSIONS: The present review attempts to provide a comprehensive
      analysis of the emerging risk biomarkers of NAFLD and NASH, and to use the
      clinical significance and analytical considerations of each biomarker pointing
      out sentinel features of disease progression.

PMID- 25575114
TI  - MR Quantitative Equilibrium Signal Mapping: A Reliable Alternative to CT in the
      Assessment of Emphysema in Patients with Chronic Obstructive Pulmonary Disease.
AB  - PURPOSE: To compare magnetic resonance (MR) quantitative equilibrium signal (qS0)
      mapping with quantitative computed tomography (CT) in the estimation of emphysema
      in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND
      METHODS: Written informed consent of the original study permitted future
      reanalysis of data. This study was a retrospective analysis of data from an
      institutional review board-approved study. Twenty-four patients with COPD and 12
      healthy patients who did not smoke underwent spirometry and two separate 1.5-T MR
      imaging examinations. All patients with COPD underwent additional chest CT. Lung
      MR qS0 maps were generated from MR images obtained with multiple inversion times
      by fitting the inversion recovery signal equation. Mean, 15th percentile, and
      standard deviation of whole-lung qS0 and relative lung area with a qS0 value
      below 0.20 (RA0.20) were measured and compared between groups with an unpaired t
      test. Reproducibility between two examinations was tested with intraclass
      correlation coefficients (ICCs), and their associations with spirometry and CT
      measurements of 15th percentile attenuation (PA15) and relative lung area with
      attenuation below -950 HU (RA-950) were assessed with the Pearson correlation
      coefficient. RESULTS: Whole-lung mean qS0 and 15th percentile of qS0 were
      significantly lower, whereas RA0.20 and standard deviation of qS0 were
      significantly higher in patients with COPD than in healthy control subjects (P =
      .014, P = .002, P = .005, and P < .001, respectively). Whole-lung mean qS0, the
      15th percentile of qS0, and RA0.20 strongly correlated with RA-950 (r = -0.78, r
      = -0.81, and r = 0.86, respectively; P < .001) and PA15 (r = 0.78, r = 0.79, and
      r = -0.71, respectively; P < .001) and moderately correlated with the ratio of
      forced expiratory volume in 1 second (FEV1) to forced vital capacity (r = 0.63, r
      = 0.67, and r = -0.60, respectively; P < .001) and percentage predicted FEV1 (r =
      0.54, r = 0.62, and r = -0.56, respectively; P <= .001). Good reproducibility of
      qS0 readouts was found in both groups (ICC range, 0.89-0.98). CONCLUSION: Lung MR
      qS0 mapping may be a reliable noncontrast nonradiation alternative to CT in the
      assessment of emphysema in patients with COPD.

PMID- 25575115
TI  - Preoperative Tomosynthesis-guided Needle Localization of Mammographically and
      Sonographically Occult Breast Lesions.
AB  - PURPOSE: To assess the feasibility and accuracy of digital breast tomosynthesis
      (DBT)-guided needle localization for DBT-detected suspicious abnormalities not
      visualized with other modalities and to analyze the imaging and pathologic
      characteristics of abnormalities detected only with DBT to determine the positive
      predictive value for malignancy. MATERIALS AND METHODS: This HIPAA-compliant
      study was approved by the institutional review board, and the requirement to
      obtain informed consent was waived. A retrospective query of the imaging database
      identified 34 consecutive women (average age, 55 years; age range, 28-84 years)
      with 36 lesions who underwent DBT-guided needle localization between April 2011
      and January 2013 with use of commercially available equipment. Imaging findings
      and medical records were reviewed. Findings that were attributable to previous
      surgical changes were classified as benign or probably benign and excluded from
      analysis because the lesions did not proceed to localization. RESULTS:
      Architectural distortion was the imaging finding identified in all 36
      abnormalities (100%). Findings from pathologic examination after the first
      attempt at localization were concordant with those from imaging in 35 of the 36
      lesions (97%), which is suggestive of appropriate sampling. Histologic findings
      were malignant in 17 of the 36 lesions (47%; 95% confidence interval: 30.4%,
      64.5%). Thirteen of the 17 lesions (76%; 95% confidence interval: 50.1%, 93.1%)
      were invasive malignancies. Twenty-two of the 36 abnormalities (61%) were either
      malignant or high-risk lesions (atypical ductal hyperplasia, lobular carcinoma in
      situ, atypical lobular hyperplasia). CONCLUSION: DBT-guided needle localization
      is an accurate and feasible method with which to biopsy DBT-detected suspicious
      architectural distortions not visualized at mammography or sonography. The high
      risk of malignancy in abnormalities detected only with DBT (47%) confirms that
      routine biopsy is required for histologic analysis.

PMID- 25575116
TI  - Two-dimensional shear-wave elastography and conventional US: the optimal
      evaluation of liver fibrosis and cirrhosis.
AB  - PURPOSE: To evaluate the individual and combined performances of two-dimensional
      (2D) shear-wave elastography (SWE) and conventional ultrasonography (US) in
      assessing liver fibrosis and cirrhosis to determine when 2D SWE should be added
      to routine US. MATERIALS AND METHODS: This prospective study was approved by the
      institutional ethics committee, and the patients provided written informed
      consent. Between April 2012 and March 2013, conventional US and 2D SWE
      examinations were performed in 198 patients (mean age, 37.7 years; age range, 18
      67 years) with chronic liver disease. Liver biopsy was used as a reference
      standard for 167 patients; the other 31 patients had decompensated liver
      cirrhosis. Receiver operating characteristic (ROC) curves were obtained to assess
      the diagnostic performance. Differences between the areas under the ROC curves
      (AUCs) were compared by using a Delong test. RESULTS: Two-dimensional SWE was
      significantly superior to US in diagnosis of significant fibrosis (score of F2 or
      greater) (AUC, 0.862 vs 0.725; P = .001) and early cirrhosis (score of F4) (AUC,
      0.926 vs 0.789; P = .007). Combining 2D SWE with US did not increase the
      performance of depicting either significant fibrosis or liver cirrhosis (P = .713
      and 0.410, respectively) relative to 2D SWE alone. There was no significant
      difference between 2D SWE and US in diagnosis of decompensated cirrhosis (AUC,
      0.878 vs 0.925; P = .323). In addition, combining 2D SWE with US did not increase
      the performance relative to that of US alone (P = .372). CONCLUSION: Conventional
      US is sufficient to detect decompensated cirrhosis. Two-dimensional SWE is
      significantly superior to US in detecting liver fibrosis. Combining 2D SWE and US
      did not improve the diagnostic performance for either fibrosis or cirrhosis.

PMID- 25575117
TI  - Advanced adenocarcinoma of the lung: comparison of CT characteristics of patients
      with anaplastic lymphoma kinase gene rearrangement and those with epidermal
      growth factor receptor mutation.
AB  - PURPOSE: To study the differences in computed tomographic (CT) characteristics
      between patients with advanced lung adenocarcinoma who have anaplastic lymphoma
      kinase (ALK) gene rearrangement and those who have epidermal growth factor
      receptor (EGFR) mutations. MATERIALS AND METHODS: This retrospective study was
      approved by the institutional review board. Informed consent was waived. Patients
      with stage IV adenocarcinoma (n = 198) were enrolled from November 2004 to
      December 2013, including 68 patients with ALK rearrangement and 130 with EGFR
      mutation. Two independent radiologists evaluated the main tumor in each patient
      and determined its size, type, margins, lymph node metastasis, and intrathoracic
      metastasis (lung, pleural or pericardial, or bone). A multiple logistic
      regression model was applied to discriminate clinical and CT characteristics
      between the types of mutation. RESULTS: The kappa index for assessment of tumor
      and node stage between radiologists was 0.8530 to 0.9388. Most of the main tumors
      in patients with both types of mutation appeared as solid masses. In univariate
      analysis, patients with an ALK rearrangement were younger (P < .001) and were
      more likely to be men (P = .001), to have never smoked (P = .002), and to have
      pleural or pericardial metastases (P < .05) compared with those with EGFR
      mutations. In multivariate analysis, lobulated margins (odds ratio, 4.815; 95%
      confidence interval [CI]: 1.789, 12.961; P = .002), N2 or N3 lymph node
      involvement (odds ratio, 2.445; 95% CI: 1.005, 5.950; P = .049), and lymphangitic
      lung metastasis (odds ratio, 8.485; 95% CI: 2.238, 32.170; P = .002) were more
      common in patients with ALK rearrangement than in those with EGFR mutation. The
      area under the receiver operating characteristic curve was 0.855. CONCLUSION:
      Adenocarcinomas with ALK rearrangement appeared as solid masses with lobulated
      margins at CT and were more likely to be associated with lymphangitic metastasis,
      advanced lymph node metastasis, and pleural or pericardial metastasis than were
      tumors with EGFR mutations.

PMID- 25575118
TI  - Improving highly accelerated fat fraction measurements for clinical trials in
      muscular dystrophy: origin and quantitative effect of R2* changes.
AB  - Purpose To investigate the effect of R2* modeling in conventional and accelerated
      measurements of skeletal muscle fat fraction in control subjects and patients
      with muscular dystrophy. Materials and Methods Eight patients with Becker
      muscular dystrophy and eight matched control subjects were recruited with
      approval from the Newcastle and North Tyneside 2 Research Ethics Committee and
      with written consent. Chemical-shift images with six widely spaced echo times (in
      3.5-msec increments) were acquired to correlate R2* and muscle fat fraction. The
      effect of incorporating or neglecting R2* modeling on fat fraction magnitude and
      variance was evaluated in a typical three-echo protocol (with 0.78-msec
      increments). Accelerated acquisitions with this protocol with 3.65*, 4.94*, and
      6.42* undersampling were reconstructed by using combined compressed sensing and
      parallel imaging and fat fraction maps produced with R2* modeling. Results Muscle
      R2* at 3.0 T (33-125 sec(-1)) depended on the morphology of fat replacement, the
      highest values occurring with the greatest interdigitation of fat. The inclusion
      of R2* modeling removed bias, which was greatest at low fat fraction, but did not
      increase variance. The 95% limits of agreement of the accelerated acquisitions
      were tight and not degraded by R2* modeling (1.65%, 1.95%, and 2.22% for 3.65*,
      4.94*, and 6.42* acceleration, respectively). Conclusion Incorporating R2*
      modeling prevents systematic errors in muscle fat fraction by up to 3.5% without
      loss of precision and should be incorporated into all muscular dystrophy studies.
      Fat fraction measurements can be accelerated fivefold by using combined
      compressed sensing and parallel imaging, modeling for R2* without loss of
      fidelity.

PMID- 25575119
TI  - Safety of MR Imaging at 1.5 T in Fetuses: A Retrospective Case-Control Study of
      Birth Weights and the Effects of Acoustic Noise.
AB  - PURPOSE: To evaluate the effects of exposure to routine magnetic resonance (MR)
      imaging at 1.5 T during pregnancy on fetal growth and neonatal hearing function
      in relation to the dose and timing of in utero exposure in a group of newborns at
      low risk for congenital hearing impairment or deafness. MATERIALS AND METHODS:
      This retrospective case-control study was approved by the local ethics committee,
      and written informed consent was waived. Between January 2008 and December 2012,
      a group of 751 neonates exposed to MR imaging in utero and a group of control
      subjects comprising 10 042 nonexposed neonates, both groups with no risk factors
      for hearing impairment at birth, were included. Neonatal hearing screening was
      performed by means of otoacoustic emission testing and auditory brain stem
      response according to national guidelines, and the prevalence of hearing
      impairment in the two groups was compared by using a noninferiority test with
      Wilson score confidence intervals. The effect of MR exposure on birth weight
      percentile was examined between the singleton neonates in the exposed group and a
      randomly chosen subset of 1805 singleton newborns of the nonexposed group by
      performing an analysis of variance. RESULTS: The rate of hearing impairment or
      deafness was found to be 0% (0 of 751) in the neonates in the exposed group and
      was not inferior to that in the nonexposed group (34 of 10 042 [0.34%], P < .05).
      There was no between-group difference in birth weight percentiles (50.6% for
      exposed vs 48.4% for nonexposed; P = .22). CONCLUSION: This study showed no
      adverse effects of exposure to 1.5-T MR imaging in utero on neonatal hearing
      function or birth weight percentiles.

PMID- 25575122
TI  - Paradigms shift when solvent-less fluids come into play.
AB  - Solvent-less organic fluids are a new class of functional soft materials. Here
      the available fluid matrix makes it equally competitive with the solvent assisted
      systems. In this Perspective, the ways in which organic fluids challenge the
      established and accepted paradigms is highlighted. In general, fundamental
      properties such as photoisomerization, energy/electron transfer, photon
      upconversion and reversible dioxygen binding are controlled by solvents and/or
      solvent polarity, the presence of oxygen etc. Here solvent-less fluids challenge
      the paradigms by realizing it under neat, solvent-less and ambient conditions.
      This new phase of research has created many potential functional materials, which
      work better and more efficiently compared to the solvent assisted systems. Hence
      this relatively new research topic and the results need special attention. Here
      we discuss a few representative examples to point out the challenges offered in
      their functioning. 

PMID- 25575123
TI  - Oxygen adsorption-induced surface segregation of titanium oxide by activation in
      carbon nanofibers for maximizing photocatalytic performance.
AB  - This research demonstrates a simple method for synthesizing titanium dioxide
      nanoparticle-decorated carbon nanofibers. These nanofibers showed highly
      efficient degradation of methylene blue under UV light because of the synergistic
      effects of the large surface-active sites of titanium dioxide nanoparticles and
      the carbon nanofibers on the photocatalytic properties. 

PMID- 25575120
TI  - MED26 regulates the transcription of snRNA genes through the recruitment of
      little elongation complex.
AB  - Regulation of transcription elongation by RNA polymerase II (Pol II) is a key
      regulatory step in gene transcription. Recently, the little elongation complex
      (LEC)-which contains the transcription elongation factor ELL/EAF-was found to be
      required for the transcription of Pol II-dependent small nuclear RNA (snRNA)
      genes. Here we show that the human Mediator subunit MED26 plays a role in the
      recruitment of LEC to a subset of snRNA genes through direct interaction of EAF
      and the N-terminal domain (NTD) of MED26. Loss of MED26 in cells decreases the
      occupancy of LEC at a subset of snRNA genes and results in a reduction in their
      transcription. Our results suggest that the MED26-NTD functions as a molecular
      switch in the exchange of TBP-associated factor 7 (TAF7) for LEC to facilitate
      the transition from initiation to elongation during transcription of a subset of
      snRNA genes. 

PMID- 25575124
TI  - Diffusiophoresis in suspensions of charged porous particles.
AB  - An analysis of the diffusiophoretic motion in a suspension of charged porous
      spheres in an electrolytic solution with a macroscopic concentration gradient is
      presented. Each porous particle can be a solvent-permeable and ion-penetrable
      charged floc or polyelectrolyte molecule, in which the densities of the fixed
      charges and frictional segments are constant, surrounded by an arbitrary electric
      double layer. The multiparticle interaction effects are considered through the
      use of a unit cell model, which allows the overlap of adjacent double layers. The
      differential equations governing the electric potential, ionic concentration, and
      fluid velocity distributions inside and outside the porous particle in a unit
      cell are linearized by assuming that the system is only slightly deviated from
      equilibrium and then solved as power expansions in its dimensionless fixed-charge
      density. A closed-form expression for the diffusiophoretic velocity of the porous
      particle correct to the second order of the fixed charge density is obtained from
      a balance between the electrostatic and hydrodynamic forces acting on it.
      Detailed comparisons of the results for the multiparticle diffusiophoresis
      obtained from the cell model with various boundary conditions are made. The
      effect of particle interactions on the diffusiophoresis, which is a linear
      combination of electrophoresis and chemiphoresis, can be significant and
      complicated in typical situations. Although the electrophoretic mobility of the
      particles decreases with an increase in the particle volume fraction, their
      chemiphoretic mobility is not necessarily a monotonic function of it. 

PMID- 25575121
TI  - Resolved single-molecule detection of individual species within a mixture of anti
      biotin antibodies using an engineered monomeric nanopore.
AB  - Oligomeric protein nanopores with rigid structures have been engineered for the
      purpose of sensing a wide range of analytes including small molecules and
      biological species such as proteins and DNA. We chose a monomeric beta-barrel
      porin, OmpG, as the platform from which to derive the nanopore sensor. OmpG is
      decorated with seven flexible loops that move dynamically to create a distinct
      gating pattern when ionic current passes through the pore. Biotin was chemically
      tethered to the most flexible one of these loops. The gating characteristic of
      the loop's movement in and out of the porin was substantially altered by analyte
      protein binding. The gating characteristics of the pore with bound targets were
      remarkably sensitive to molecular identity, even providing the ability to
      distinguish between homologues within an antibody mixture. A total of five gating
      parameters were analyzed for each analyte to create a unique fingerprint for each
      biotin-binding protein. Our exploitation of gating noise as a molecular
      identifier may allow more sophisticated sensor design, while OmpG's monomeric
      structure greatly simplifies nanopore production. 

PMID- 25575127
TI  - Arginine kinase in the cladoceran Daphnia magna: cDNA sequencing and expression
      is associated with resistance to toxic Microcystis.
AB  - Nutrient loading derived from anthropogenic activities into lakes have increased
      the frequency, severity and duration of toxic cyanobacterial blooms around the
      world. Although herbivorous zooplankton are generally considered to be unable to
      control toxic cyanobacteria, populations of some zooplankton, including Daphnia,
      have been shown to locally adapt to toxic cyanobacteria and suppress
      cyanobacterial bloom formation. However, little is known about the physiology of
      zooplankton behind this phenomenon. One possible explanation is that some
      zooplankton may induce more tolerance by elevating energy production, thereby
      adding more energy allocation to detoxification expenditure. It is assumed that
      arginine kinase (AK) serves as a core in temporal and spatial adenosine
      triphosphate (ATP) buffering in cells with high fluctuating energy requirements.
      To test this hypothesis, we studied the energetic response of a single Daphnia
      magna clone exposed to a toxic strain of Microcystis aeruginosa, PCC7806.
      Arginine kinase of D. magna (Dm-AK) was successfully cloned. An ATP-gua PtransN
      domain which was described as a guanidine substrate specificity domain and an ATP
      gua Ptrans domain which was responsible for binding ATP were both identified in
      the Dm-AK. Phylogenetic analysis of AKs in a range of arthropod taxa suggested
      that Dm-AK was as dissimilar to other crustaceans as it was to insects. Dm-AK
      transcript level and ATP content in the presence of M. aeruginosa were
      significantly lower than those in the control diet containing only the nutritious
      chlorophyte, Scenedesmus obliquus, whereas the two parameters in the neonates
      whose mothers had been previously exposed to M. aeruginosa were significantly
      higher than those of mothers fed with pure S. obliquus. These findings suggest
      that Dm-AK might play an essential role in the coupling of energy production and
      utilization and the tolerance of D. magna to toxic cyanobacteria. 

PMID- 25575125
TI  - Future directions in research on sexual minority adolescent mental, behavioral,
      and sexual health.
AB  - This article describes current knowledge on sexual, mental, and behavioral health
      of sexual minority (SM) youth and identifies gaps that would benefit from future
      research. A translational sciences framework is used to conceptualize the
      article, discussing findings and gaps along the spectrum from basic research on
      prevalence and mechanisms, to intervention development and testing, to
      implementation. Relative to adults, there has been much less research on
      adolescents and very few studies that had longitudinal follow-up beyond 1 year.
      Due to historical changes in the social acceptance of the SM community, new
      cohorts are needed to represent contemporary life experiences and associated
      health consequences. Important theoretical developments have occurred in
      conceptualizing mechanisms that drive SM health disparities and mechanistic
      research is underway, including studies that identify individual and structural
      risk/protective factors. Research opportunities exist in the utilization of
      sibling-comparison designs, inclusion of parents, and studying romantic
      relationships. Methodological innovation is needed in sampling SM populations.
      There has been less intervention research and approaches should consider natural
      resiliencies, life-course frameworks, prevention science, multiple levels of
      influence, and the importance of implementation. Regulatory obstacles are created
      when ethics boards elect to require parental permission and ethics research is
      needed. There has been inconsistent inclusion of SM populations in the definition
      of "health disparity population," which impacts funding and training
      opportunities. There are incredible opportunities for scholars to make
      substantial and foundational contributions to help address the health of SM
      youth, and new funding opportunities to do so.

PMID- 25575129
TI  - Role of arginine in mediating protein-carbon nanotube interactions.
AB  - Arginine-rich proteins (e.g., lysozyme) or poly-L-arginine peptides have been
      suggested as solvating and dispersing agents for single-wall carbon nanotubes
      (CNTs) in water. In addition, protein structure-function in porous and
      hydrophobic materials is of broad interest. The amino acid residue, arginine
      (Arg(+)), has been implicated as an important mediator of protein/peptide-CNT
      interactions. To understand the structural and thermodynamic aspects of this
      interaction at the molecular level, we employ molecular dynamics (MD) simulations
      of the protein lysozyme in the interior of a CNT, as well as of free solutions of
      Arg(+) in the presence of a CNT. To dissect the Arg(+)-CNT interaction further,
      we also perform simulations of aqueous solutions of the guanidinium ion (Gdm(+))
      and the norvaline (Nva) residue in the presence of a CNT. We show that the
      interactions of lysozyme with the CNT are mediated by the surface Arg(+)
      residues. The strong interaction of Arg(+) residue with the CNT is primarily
      driven by the favorable interactions of the Gdm(+) group with the CNT wall. The
      Gdm(+) group is not as well-hydrated on its flat sides, which binds to the CNT
      wall. This is consistent with a similar binding of Gdm(+) ions to a hydrophobic
      polymer. In contrast, the Nva residue, which lacks the Gdm(+) group, binds to the
      CNT weakly. We present details of the free energy of binding, molecular
      structure, and dynamics of these solutes on the CNT surface. Our results
      highlight the important role of Arg(+) residues in protein-CNT or protein-carbon
      based material interactions. Such interactions could be manipulated precisely
      through protein engineering, thereby offering control over protein orientation
      and structure on CNTs, graphene, or other hydrophobic interfaces.

PMID- 25575128
TI  - A novel "priming-boosting" strategy for immune interventions in cervical cancer.
AB  - Despite the encouraging development of a preventive vaccine for human
      papillomavirus (HPV), it cannot improve ongoing infections. Therefore, a new
      vaccine is urgently needed that can prevent and treat cervical cancer, and cure
      pre-cancerous lesions. In this study, we constructed two peptide-based vaccines.
      The first was a short-term, long-peptide (ST-LP) vaccine that simultaneously
      targeted three key carcinogenic epitopes (E5-E6-E7) on HPV16. We tested this
      vaccine in murine TC-1 cells infected with a recombinant adeno-associated virus
      (rAAV) fused with HPV16E5 DNA (rTC-1 cells), which served as a cell model; we
      also tested it in immune-competent mice loaded with rTC-1 cells, which served as
      an ectopic tumor model. The ST-LP injections resulted in strong, cell-mediated
      immunity, capable of attacking and eliminating abnormal antigen-bearing cells.
      Furthermore, to prolong immunogenic capability, we designed a unique rAAV that
      encoded the three predicted epitopes for a second, long-term, long-peptide (LT
      LP) vaccine. Moreover, we used a new immune strategy of continuous re-injections,
      where three ST-LP injections were performed at one-week intervals (days 0, 7,
      14), then one LT-LP injection was performed on day 120. Our in vitro and in vivo
      studies revealed that this strategy could boost the immune response to produce
      longer and stronger protection against target cells, and mice were thoroughly
      protected from tumor growth. Our results showed that priming the immune system
      with the ST-LP vaccine, followed by boosting the immune system with the LT-LP
      vaccine could generate a rapid, robust, durable cytotoxic T-lymphocyte response
      to HPV16-positive tumors. 

PMID- 25575130
TI  - A mitochondria-targetable fluorescent probe for peroxynitrite: fast response and
      high selectivity.
AB  - A mitochondria-targetable fluorescence probe, methyl(4-hydroxyphenyl)amino
      substituted pyronin (1), was exploited, which could highly selectively sense
      peroxynitrite (ONOO(-)) within seconds.

PMID- 25575131
TI  - Tau proteins in the temporal and frontal cortices in patients with vascular
      dementia.
AB  - We previously reported that, in the brains of older patients with vascular
      dementia (VaD), there is a distinctive accumulation of detergent-extractable
      soluble amyloid-beta, with a predominance of Abeta42 species. It is unclear,
      however, if tau proteins also accumulate in the brains of older VaD subjects.
      Using antibody-specific immunoassays, we assessed concentrations of total tau (t
      tau) and phosphorylated tau protein, measured at 3 phosphorylated sites (i.e.
      Thr181, Ser202/Thr205, and Ser262), as well as synaptophysin in the temporal and
      frontal cortices of 18 VaD, 16 Alzheimer disease (AD), and 16 normal age-matched
      control subjects. There was selective loss of t-tau protein in VaD compared with
      controls and AD subjects (p < 0.021 and p < 0.001, respectively). In contrast,
      phosphorylated tau levels were similar to controls in VaD in both regions, but
      they were increased in the temporal lobes of patients with AD (p < 0.01 and p <
      0.0001 for Ser202/Thr205 and Ser262 phosphorylated sites, respectively). The
      reduced t-tau in the VaD group was unrelated to any low-level neurofibrillary or
      amyloid pathology or age at death. These findings suggest that breaches of
      microvascular or microstructural tissue integrity subsequent to ischemic injury
      in older age may modify tau protein metabolism or phosphorylation and have
      effects on the burden of neurofibrillary pathology characteristic of AD. 

PMID- 25575132
TI  - High-resolution genomic analysis does not qualify atypical plexus papilloma as a
      separate entity among choroid plexus tumors.
AB  - Choroid plexus tumors are rare neoplasms that mainly affect children. They
      include papillomas, atypical papillomas, and carcinomas. Detailed genetic studies
      are rare, and information about their molecular pathogenesis is limited.
      Molecular inversion probe analysis is a hybridization-based method that
      represents a reliable tool for the analysis of highly fragmented formalin-fixed
      paraffin-embedded tissue-derived DNA. Here, analysis of 62 cases showed frequent
      hyperdiploidy in papillomas and atypical papillomas that appeared very similar in
      their cytogenetic profiles. In contrast, carcinomas showed mainly losses of
      chromosomes. Besides recurrent focal chromosomal gains common to all choroid
      plexus tumors, including chromosome 14q21-q22 (harboring OTX2), chromosome 7q22
      (LAMB1), and chromosome 9q21.12 (TRPM3), Genomic Identification of Significant
      Targets in Cancer analysis uncovered focal alterations specific for papillomas
      and atypical papillomas (e.g. 7p21.3 [ARL4A]) and for carcinomas (16p13.3
      [RBFOX1] and 6p21 [POLH, GTPBP2, RSPH9, and VEGFA]). Additional RNA expression
      profiling and gene set enrichment analysis revealed greater expression of cell
      cycle-related genes in atypical papillomas in comparison with that in papillomas.
      These findings suggest that atypical papillomas represent an immature variant of
      papillomas characterized by increased proliferative activity, whereas carcinomas
      seem to represent a genetically distinct tumor group. 

PMID- 25575133
TI  - Progranulin reduction is associated with increased tau phosphorylation in P301L
      tau transgenic mice.
AB  - Granulin (GRN) mutations have been identified in familial frontotemporal lobar
      degeneration patients with ubiquitin pathology. GRN transcript haploinsufficiency
      is proposed as a disease mechanism that leads to the loss of functional
      progranulin (PGRN) protein. Thus, these mutations are strongly involved in
      frontotemporal lobar degeneration pathogenesis. Moreover, recent findings
      indicate that GRN mutations are associated with other neurodegenerative disorders
      with tau pathology, including Alzheimer disease and corticobasal degeneration. To
      investigate the potential influence of a decline in PGRN protein on tau
      accumulation, P301L tau transgenic mice were interbred with GRN-deficient mice,
      producing P301L tau transgenic mice harboring the GRN hemizygote. Brains were
      collected from 13- and 19-month-old mice, and sequential extraction of proteins,
      immunoblotting, and immunohistochemical analyses were performed. Immunoblotting
      analysis revealed that tau phosphorylation was accelerated in the Tris-saline
      soluble fraction of 13-month-old and in the sarkosyl-insoluble fraction of 19
      month-old P301L tau/GRN hemizygotes compared with those in fractions from P301L
      tau transgenic mice. Activity of cyclin-dependent kinases was also upregulated in
      the brains of P301L tau/GRN hemizygote mice. Although the mechanisms involved in
      these findings remain unknown, our data suggest that a reduction in PGRN protein
      might contribute to phosphorylation and intraneuronal accumulation of tau. 

PMID- 25575134
TI  - Notch signaling activation in pediatric low-grade astrocytoma.
AB  - Pilocytic astrocytoma (PA) is the most common primary brain tumor in children;
      various signaling pathways have been implicated in its biology. The Notch
      signaling pathway has been found to play a role in the development, stem cell
      biology, and pathogenesis of several cancers, but its role in PA has not been
      investigated. We studied alterations in Notch signaling components in tumor
      tissue from 18 patients with PA and 4 with other low-grade astrocytomas to
      identify much needed therapeutic targets. We found that Notch pathway members
      were overexpressed at the mRNA (NOTCH1, NOTCH2, HEY1, HEY2) and protein (HES1)
      levels in PAs at various anatomic sites compared with non-neoplastic brain
      samples. These changes were not associated with specific BRAF alterations.
      Inhibiting the Notch pathway in the pediatric low-grade astrocytoma cell lines
      Res186 and Res259 using either RNA interference or a gamma-secretase inhibitor
      resulted in variable, but significant, reduction in cell growth and migration.
      This study suggests a potential role for Notch signaling in pediatric low-grade
      astrocytoma tumorigenesis and that Notch signaling may be a viable pathway
      therapeutic target. 

PMID- 25575135
TI  - Cerebral cortical Abeta42 and PHF-tau in 325 consecutive brain autopsies
      stratified by diagnosis, location, and APOE.
AB  - We used a novel approach to molecular quantification in standard fixed and
      embedded tissue to measure amyloid beta 42 (Abeta(42)) and paired helical
      filament-tau (PHF-tau) in frontal, temporal, and parietal cortices from 325
      consecutive brain autopsies collected as part of a population-based study of
      brain aging and incident dementia in the Seattle area. We observed significant
      effects of APOE epsilon4 on Abeta(42) levels in both diagnostic groups by disease
      stage and region. In contrast, we did not observe a significant effect of APOE
      epsilon4 on PHF-tau levels by disease stage in any region. Levels of Abeta(42)
      and PHF-tau in cerebral cortex were correlated more strongly in the Dementia
      group, and these measures had independent explanatory power for dementia beyond
      those of standard neuropathologic indices. Associations between Lewy body disease
      and Abeta(42) or PHF-tau levels and between Abeta(42) levels and microvascular
      brain injury suggested that these comorbid diseases enhanced the penetrance of
      Alzheimer disease. Our novel approach brings additional insights into the
      molecular pathogenesis of common causes of dementia and may serve as a platform
      for future studies pursuing associations between molecular changes in Alzheimer
      disease and genetic or environmental risk.

PMID- 25575137
TI  - Adenosine kinase expression in cortical dysplasia with balloon cells: analysis of
      developmental lineage of cell types.
AB  - Focal cortical dysplasia type IIB (FCDIIB) is a developmental malformation of the
      cerebral cortex that is associated with pharmacoresistant epilepsy.
      Overexpression of adenosine kinase (ADK) has been regarded as a pathologic
      hallmark of epilepsy. We hypothesized that the epileptogenic mechanisms
      underlying FCDIIB are related to abnormal ADK expression. We used
      immunohistochemistry to examine the expression of ADK and of heterogeneous cell
      population markers of astrocytes (glial fibrillary acidic protein), immature glia
      (vimentin), immature neurons (neuronal class III beta-tubulin, TUJ1),
      multipotential progenitor cells (nestin), mature neurons (microtubule-associated
      protein 2), and antiapoptotic gene products (Bcl-2) in surgically resected human
      epileptic cortical specimens from FCDIIB patients (n = 20). Expression patterns
      were compared with those in normal autopsy (n = 6) and surgical control (n = 6)
      brain samples. Balloon cells in FCDII lesions were immunoreactive for ADK (77%)
      and balloon cells expressing the different cell markers expressing different
      degrees of ADK. Adenosine kinase expression assessed by Western blot and
      enzymatic activity were also greater in FCD versus control samples. These results
      suggest that upregulation of ADK is a common pathologic component of FCDIIB.
      Adenosine kinase might, therefore, be a target in the treatment of epilepsy
      associated with FCD. 

PMID- 25575138
TI  - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive
      to steroids (CLIPPERS): postmortem findings.

PMID- 25575136
TI  - Friedreich ataxia: failure of GABA-ergic and glycinergic synaptic transmission in
      the dentate nucleus.
AB  - Atrophy of large neurons in the dentate nucleus (DN) is an important pathologic
      correlate of neurologic disability in patients with Friedreich ataxia (FA).
      Thinning of the DN was quantified in 29 autopsy cases of FA and 2 carriers by
      measuring the thickness of the gray matter ribbon on stains with anti-glutamic
      acid decarboxylase, the rate-limiting enzyme in the biosynthesis of gamma-amino
      butyric acid (GABA). The DN was thinner than normal in all cases of FA, and
      atrophy correlated inversely with disease duration but not with age at onset or
      length of the homozygous guanine-adenine-adenine trinucleotide expansions. In 13
      of the FA cases, frozen DN tissue was available for assay of frataxin. Dentate
      nucleus atrophy was more severe when frataxin was very low. Immunohistochemical
      staining for glutamic acid decarboxylase revealed grumose reaction and
      preservation of small GABA-ergic neurons in the DN of FA patients. Residual small
      DN neurons and varicose axons also contained the glycine transporter 2,
      identifying them as glycinergic. Immunohistochemistry also confirmed severe loss
      of GABA-A and glycine receptors in the DN with comparable depletion of the
      receptor-anchoring protein gephyrin. Thus, loss of gephyrin and failure to
      position GABA-A and glycine receptors correctly may reduce trophic support of
      large DN neurons and contribute to their atrophy. By contrast, Purkinje cells may
      escape retrograde atrophy in FA by issuing new axonal sprouts to small surviving
      DN neurons where they form reparative grumose clusters. 

PMID- 25575140
TI  - Does ischemia-reperfusion injury affect ovarian reserve and follicle viability in
      a rat model with adnexal torsion?
AB  - OBJECTIVE(S): To evaluate the effect of ischemia-reperfusion on follicle count
      and viability of follicles in a rat model with adnexal torsion. STUDY DESIGN: A
      total of 24 female adult Wistar albino rats were included in the study. In the
      first laparotomy, right ovaries were twisted at 720 degrees  in the
      counterclockwise for a duration of two (n=12), four (n=6) or 16 hours (n=6),
      whereas contralateral sites were kept as controls. In the second laparotomy, the
      right ovaries were detorsioned. Twenty-eight days after the detorsion, both
      ovaries were retrieved with the third laparotomy and placed in formaldehyde for
      subsequent examination under light microscopy and immunohistochemistry for
      proliferating cell nuclear antigen (PCNA). Besides histological evaluation by
      only using a standard scoring system, the viability of the follicles was also
      assessed by PCNA with immunohistochemical staining. RESULTS: Macroscopically,
      after two, four and 16 hours of torsion, all the twisted ovaries had enlarged and
      demonstrated a dark, dusky appearance. However, under light microscopy with 10X
      magnification, the mean primordial+primary follicle count was comparable in
      twisted and control sides (26.7+/-7.6 vs. 28.1+/-5.9 respectively). In terms of
      the means of total tissue damage, only the loss of cohesion was found to be
      significantly different compared to the control sides (2.78+/-0.86 vs. 2.17+/
      0.86, p=0.017). Immunohistochemical staining revealed significantly lower PCNA
      counts in the 16-hour torsion group only. CONCLUSION(S): Even though ovarian
      reserves, reflected by primordial and primary follicle count, are similar between
      torsioned and contralateral ovaries, the viability of the remaining follicles
      might be affected by a long-standing ischemia-reperfusion phenomenon. Follicle
      count may reflect an idea of fertility potential, but immunohistochemical
      staining using viability markers such as PCNA confirms the viability of the
      counted follicles and appears to be a more precise approach necessary for
      demonstrating the functional status.

PMID- 25575139
TI  - The chromatin-modifying protein HMGA2 promotes atypical teratoid/rhabdoid cell
      tumorigenicity.
AB  - Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive pediatric central
      nervous system tumor. The poor prognosis of AT/RT warrants identification of
      novel therapeutic targets and strategies. High-mobility Group AT-hook 2 (HMGA2)
      is a developmentally important chromatin-modifying protein that positively
      regulates tumor growth, self-renewal, and invasion in other cancer types. High
      mobility group A2 was recently identified as being upregulated in AT/RT tissue,
      but the role of HMGA2 in brain tumors remains unknown. We used lentiviral short
      hairpin RNA to suppress HMGA2 in AT/RT cell lines and found that loss of HMGA2
      led to decreased cell growth, proliferation, and colony formation and increased
      apoptosis. We also found that suppression of HMGA2 negatively affected in vivo
      orthotopic xenograft tumor growth, more than doubling median survival of mice
      from 58 days to 153 days. Our results indicate a role for HMGA2 in AT/RT in vitro
      and in vivo and demonstrate that HMGA2 is a potential therapeutic target in these
      lethal pediatric tumors. 

PMID- 25575141
TI  - Smoking and the correlation between birth weight and placental weight. Evidence
      of interaction with maternal haptoglobin phenotype.
AB  - OBJECTIVE: The negative effects of cigarette smoking on human reproduction are
      well known. In a previous paper we have reported that negative effects of smoking
      on fertility are observed in women carrying the Haptoglobin (Hp) 2 phenotype
      only. In the present note we have examined the effect of smoking on the
      correlation between birth weight (BW) and placental weight (PW) and the
      interaction with maternal Hp phenotype. STUDY DESIGN: We have studied 584
      consecutive newborns and their healthy mothers from the White population of the
      central area of Italy. Written informed consent was obtained by mothers to
      participate to this investigation that was approved by the Department of
      Pediatrics. Maternal Hp phenotype was determined by the method of Smithies as
      previously described. Differences between correlation coefficients were evaluated
      according to Snedecor and Cochran and according to Soper. Difference between
      means was calculated by Student's-t test using commercial software (SPSS).
      RESULTS: A strong decrease of correlation is seen in smoking mothers with Hp 2
      phenotype only (p<0.0001). No statistically significant effect of smoking is
      present in mothers with Hp1 or Hp2-1 phenotype. A statistically significant
      decrease of BW in smoking mothers is observed in both Hp 2 mothers and in mothers
      carrying the Hp*1 allele. On the contrary a decrease of PW is observed only in
      mothers carrying Hp*1 allele but not in Hp 2 mothers. This indicates a concordant
      effect of smoking on BW and PW in mothers carrying Hp*1 allele but a discordant
      effect of BW and PW in Hp 2 mothers. This could explain the lack of correlation
      between BW and PW in smoking mothers carrying the Hp 2 phenotype. CONCLUSION: The
      combined phenotype smoking-Hp 2 shows different effects on BW and PW. Hp 2 has no
      effect on the decrease of BW determined by smoking but shows important effect in
      neutralizing the decrease of PW due to smoking: Hp polymorphism may be a factor
      with protective effects prevalent on placental growth as compared to fetal
      growth.

PMID- 25575142
TI  - National MTM Advisory Board comments on stakeholder proceedings on community
      pharmacy and managed care partnerships in quality.

PMID- 25575143
TI  - Standards for compounding of oral liquids for pediatric patients.

PMID- 25575144
TI  - Response: standards for compounding of oral liquids for pediatric patients.

PMID- 25575145
TI  - Corrections.

PMID- 25575146
TI  - Medical marijuana: policy topic for 2015 APhA House of Delegates.

PMID- 25575147
TI  - Being open to missed opportunities.

PMID- 25575148
TI  - Are community-based pharmacists underused in the care of persons living with HIV?
      A need for structural and policy changes.
AB  - OBJECTIVE: To describe community pharmacists' perceptions on their current role
      in direct patient care services, an expanded role for pharmacists in providing
      patient care services, and changes needed to optimally use pharmacists' expertise
      to provide high-quality direct patient care services to people living with human
      immunodeficiency virus (HIV) infections. DESIGN: Cross-sectional study. SETTING:
      Four Midwestern cities in the United States in August through October 2009.
      PARTICIPANTS: 28 community-based pharmacists practicing in 17 pharmacies.
      INTERVENTIONS: Interviews. MAIN OUTCOME MEASURES: Opinions of participants about
      roles of specialty and nonspecialty pharmacists in caring for patients living
      with HIV infections. RESULTS: Pharmacists noted that although challenges in our
      health care system characterized by inaccessible health professionals presented
      opportunities for a greater pharmacist role, there were missed opportunities for
      greater level of patient care services in many community-based nonspecialty
      settings. Many pharmacists in semispecialty and nonspecialty pharmacies expressed
      a desire for an expanded role in patient care congruent with their pharmacy
      education and training. CONCLUSION: Structural-level policy changes needed to
      transform community-based pharmacy settings to patient-centered medical homes
      include recognizing pharmacists as important players in the multidisciplinary
      health care team, extending the health information exchange highway to include
      pharmacist-generated electronic therapeutic records, and realigning financial
      incentives. Comprehensive policy initiatives are needed to optimize the use of
      highly trained pharmacists in enhancing the quality of health care to an ever
      growing number of Americans with chronic conditions who access care in community
      based pharmacy settings.

PMID- 25575150
TI  - Charitable pharmacy services: Impact on patient-reported hospital use, medication
      access, and health status.
AB  - OBJECTIVE: To evaluate the impact that Charitable Pharmacy of Central Ohio
      (CPCO), a pharmacy providing free pharmacy services and medications, had on an
      indigent patient population by determining the change in patient-reported
      hospital use, ability to access medications, and perception of health status
      after receiving CPCO services. DESIGN: Cross-sectional study with face-to-face
      interviews using a convenience sample. SETTING: Columbus, OH, in January to March
      2013. PATIENTS: 206 English-speaking patients 18 years or older at CPCO.
      INTERVENTION: Free pharmacy services and medications provided by CPCO. MAIN
      OUTCOMES MEASURES: Number of patient-reported hospital visits before and after
      CPCO use. RESULTS: In the year before using CPCO, patients reported using the
      hospital a mean of 2.36 (median, 2.00) times per year versus 1.33 (median, 0.67)
      times per year after, a decrease of 1.03 hospital visits per year per patient.
      Before coming to CPCO, 41% of patients were able to have all of their prescribed
      medications filled; this rose to 85% after using CPCO. A total of 89% of patients
      reported that not only was their overall health was better, but they also had a
      better understanding of their medications and believed they were in more control
      of their own health since receiving CPCO services. CONCLUSION: A charitable
      pharmacy model has the potential to decrease health care costs and empower
      patients to be more in control of their health.

PMID- 25575149
TI  - Nonprescription syringe sales: a missed opportunity for HIV prevention in
      California.
AB  - OBJECTIVE: To assess implementation of California Senate Bill SB41 in two inland
      California counties where prevalence of injection drug use is among the highest
      in the nation. DESIGN: Syringe purchase trial. SETTING: Fresno and Kern counties,
      California. PARTICIPANTS: All 248 community pharmacies in the counties. MAIN
      OUTCOME MEASURE: Successful or unsuccessful syringe purchase attempt. RESULTS:
      Only 52 (21.0%) syringe purchase attempts were successful. The proportion of
      successful attempts did not vary by county or by data collector ethnicity. The
      most common reasons for unsuccessful syringe purchase attempts were prescription
      requirements (45.7%), the requested syringe size was not available (10.7%), and
      the pharmacy did not sell syringes (9.7%). In addition, some syringe purchase
      attempts (4.1%) were unsuccessful because the data collector was asked to
      purchase more syringes than allowed by law. Although 80% and 78% of Fresno and
      Kern residents, respectively, live within a 5-minute drive of a community
      pharmacy, less than one-half live within a 5-minute drive of a community pharmacy
      that sold syringes. CONCLUSION: SB41 has not resulted in broad pharmacy-based
      syringe access in California's inland counties, where a disproportionate number
      of cases of human immunodeficiency virus (HIV) infections are associated with
      injection drug use. Additional steps by legislative bodies, regulatory agencies,
      and professional organizations are needed to actively engage pharmacies in
      expanding nonprescription syringe sales to reduce HIV transmission among
      injection drug users.

PMID- 25575151
TI  - Journal of the American Pharmacists Association guidelines for authors.

PMID- 25575153
TI  - Immunization information systems: A decade of progress.

PMID- 25575154
TI  - New drugs: dulaglutide, olodaterol hydrochloride, and vorapaxar sulfate.

PMID- 25575155
TI  - Medication therapy management: primum non nocere.

PMID- 25575157
TI  - Correction: a 'terror of tyrannosaurs': the first trackways of tyrannosaurids and
      evidence of gregariousness and pathology in tyrannosauridae.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0103613.]. 

PMID- 25575159
TI  - Modeling of temperature profiles in an environmental transmission electron
      microscope using computational fluid dynamics.
AB  - The temperature and velocity field, pressure distribution, and the temperature
      variation across the sample region inside an environmental transmission electron
      microscope (ETEM) have been modeled by means of computational fluid dynamics
      (CFD). Heating the sample area by a furnace type TEM holder gives rise to
      temperature gradients over the sample area. Three major mechanisms have been
      identified with respect to heat transfer in the sample area: radiation from the
      grid, conduction in the grid, and conduction in the gas. A parameter sensitivity
      analysis showed that the sample temperature was affected by the conductivity of
      the gas, the emissivity of the sample grid, and the conductivity of the grid.
      Ideally the grid should be polished and made from a material with good
      conductivity, e.g. copper. With hydrogen gas, which has the highest conductivity
      of the gases studied, the temperature difference over the TEM grid is less than 5
      degrees C, at what must be considered typical conditions, and it is concluded
      that the conditions on the sample grid in the ETEM can be considered as
      isothermal during general use.

PMID- 25575156
TI  - Interaction between arsenic exposure from drinking water and genetic
      polymorphisms on cardiovascular disease in Bangladesh: a prospective case-cohort
      study.
AB  - BACKGROUND: Epidemiologic data on genetic susceptibility to cardiovascular
      effects of arsenic exposure from drinking water are limited. OBJECTIVE: We
      investigated whether the association between well-water arsenic and
      cardiovascular disease (CVD) differed by 170 single nucleotide polymorphisms
      (SNPs) in 17 genes related to arsenic metabolism, oxidative stress, inflammation,
      and endothelial dysfunction. METHOD: We conducted a prospective case-cohort study
      nested in the Health Effects of Arsenic Longitudinal Study, with a random
      subcohort of 1,375 subjects and 447 incident fatal and nonfatal cases of CVD.
      Well-water arsenic was measured in 2000 at baseline. The CVD cases, 56 of which
      occurred in the subcohort, included 238 coronary heart disease cases, 165 stroke
      cases, and 44 deaths due to other CVD identified during follow-up from 2000 to
      2012. RESULTS: Of the 170 SNPs tested, multiplicative interactions between well
      water arsenic and two SNPs, rs281432 in ICAM1 (padj = 0.0002) and rs3176867 in
      VCAM1 (padj = 0.035), were significant for CVD after adjustment for multiple
      testing. Compared with those with GC or CC genotype in rs281432 and lower well
      water arsenic, the adjusted hazard ratio (aHR) for CVD was 1.82 (95% CI: 1.31,
      2.54) for a 1-SD increase in well-water arsenic combined with the GG genotype,
      which was greater than expected given aHRs of 1.08 and 0.96 for separate effects
      of arsenic and the genotype alone, respectively. Similarly, the joint aHR for
      arsenic and the rs3176867 CC genotype was 1.34 (95% CI: 0.95, 1.87), greater than
      expected given aHRs for their separate effects of 1.02 and 0.84, respectively.
      CONCLUSIONS: Associations between CVD and arsenic exposure may be modified by
      genetic variants related to endothelial dysfunction.

PMID- 25575160
TI  - Conformational flexibility of fused tetracenedione propellers obtained from one
      pot reductive dimerization of acetylenic quinones.
AB  - Reductive dimerization of acetylenic anthraquinones provides synthetic access to
      flexible nonplanar polyaromatics with a tetracenedione core. In solution, these
      nonplanar, contorted polycycles exist as equilibrating mixtures of two symmetric
      conformers. The fused tetracenediones are easily reduced and exhibit rich
      electrochemical behavior. 

PMID- 25575161
TI  - Structural comparisons of ligand-gated ion channels in open, closed, and
      desensitized states identify a novel propofol-binding site on mammalian gamma
      aminobutyric acid type A receptors.
AB  - BACKGROUND: Most anesthetics, particularly intravenous agents such as propofol
      and etomidate, enhance the actions of the neurotransmitter gamma-aminobutyric
      acid (GABA) at the GABA type A receptor. However, there is no agreement as where
      anesthetics bind to the receptor. A novel approach would be to identify regions
      on the receptor that are state-dependent, which would account for the ability of
      anesthetics to affect channel opening by binding differentially to the open and
      closed states. METHODS: The open and closed structures of the GABA type A
      receptor homologues Gloeobacter ligand-gated ion channel and glutamate-gated
      chloride channel were compared, and regions in the channels that move on channel
      opening and closing were identified. Docking calculations were performed to
      investigate possible binding of propofol to the GABA type A beta3 homomer in this
      region. RESULTS: A comparison between the open and closed states of the
      Gloeobacter ligand-gated ion channel and glutamate-gated chloride channel
      channels identified a region at the top of transmembrane domains 2 and 3 that
      shows maximum movement when the channels transition between the open and closed
      states. Docking of propofol into the GABA type A beta3 homomer identified two
      putative binding cavities in this same region, one with a high affinity and one
      with a lower affinity. Both cavities were adjacent to a histidine residue that
      has been photolabeled by a propofol analog, and both sites would be disrupted on
      channel closing. CONCLUSIONS: These calculations support the conclusion of a
      recent photolabeling study that propofol acts at a site at the interface between
      the extracellular and transmembrane domains, close to the top of transmembrane
      domain 2.

PMID- 25575158
TI  - Septic acute kidney injury: molecular mechanisms and the importance of
      stratification and targeting therapy.
AB  - The most common cause of acute kidney injury (AKI) in hospitalized patients is
      sepsis. However, the molecular pathways and mechanisms that mediate septic AKI
      are not well defined. Experiments performed over the past 20 years suggest that
      there are profound differences in the pathogenesis between septic and ischemic
      AKI. Septic AKI often occurs independently of hypoperfusion, and is mediated by a
      concomitant pro- and anti-inflammatory state that is activated in response to
      various pathogen-associated molecular patterns, such as endotoxin, as well as
      damage-associated molecular patterns. These molecular patterns are recognized by
      Toll-like receptors (TLRs) found in the kidney, and effectuate downstream
      inflammatory pathways. Additionally, apoptosis has been proposed to play a role
      in the pathogenesis of septic AKI. However, targeted therapies designed to
      mitigate the above aspects of the inflammatory state, TLR-related pathways, and
      apoptosis have failed to show significant clinical benefit. This failure is
      likely due to the protean nature of septic AKI, whereby different patients
      present at different points along the immunologic spectrum. While one patient may
      benefit from targeted therapy at one end of the spectrum, another patient at the
      other end may be harmed by the same therapy. We propose that a next important
      step in septic AKI research will be to identify where patients lie on the
      immunologic spectrum in order to appropriately target therapies at the
      inflammatory cascade, TLRs, and possibly apoptosis. 

PMID- 25575162
TI  - Images in Anesthesiology: Detection of Large Inferior Thyroid Artery by
      Ultrasound Prescan before Internal Jugular Vein Catheterization.

PMID- 25575163
TI  - Repeated exposure to ketamine-xylazine during early development impairs motor
      learning-dependent dendritic spine plasticity in adulthood.
AB  - BACKGROUND: Recent studies in rodents suggest that repeated and prolonged
      anesthetic exposure at early stages of development leads to cognitive and
      behavioral impairments later in life. However, the underlying mechanism remains
      unknown. In this study, we tested whether exposure to general anesthesia during
      early development will disrupt the maturation of synaptic circuits and compromise
      learning-related synaptic plasticity later in life. METHODS: Mice received
      ketamine-xylazine (20/3 mg/kg) anesthesia for one or three times, starting at
      either early (postnatal day 14 [P14]) or late (P21) stages of development (n =
      105). Control mice received saline injections (n = 34). At P30, mice were
      subjected to rotarod motor training and fear conditioning. Motor learning-induced
      synaptic remodeling was examined in vivo by repeatedly imaging fluorescently
      labeled postsynaptic dendritic spines in the primary motor cortex before and
      after training using two-photon microscopy. RESULTS: Three exposures to ketamine
      xylazine anesthesia between P14 and P18 impair the animals' motor learning and
      learning-dependent dendritic spine plasticity (new spine formation, 8.4 +/- 1.3%
      [mean +/- SD] vs. 13.4 +/- 1.8%, P = 0.002) without affecting fear memory and
      cell apoptosis. One exposure at P14 or three exposures between P21 and P25 has no
      effects on the animals' motor learning or spine plasticity. Finally, enriched
      motor experience ameliorates anesthesia-induced motor learning impairment and
      synaptic deficits. CONCLUSIONS: Our study demonstrates that repeated exposures to
      ketamine-xylazine during early development impair motor learning and learning
      dependent dendritic spine plasticity later in life. The reduction in synaptic
      structural plasticity may underlie anesthesia-induced behavioral impairment.

PMID- 25575164
TI  - Micelle stabilization via entropic repulsion: balance of force directionality and
      geometric packing of subunit.
AB  - Nanoparticles, 10-30 nm in size, have shown great prospects as nanocarriers for
      drug delivery. We designed amphiphiles based on 3-helix peptide-PEG conjugate
      forming 15 nm micelles (defined as "3-helix micelles") with good in vivo
      stability. Here, we investigated the effect of the site of PEG conjugation on the
      kinetic stability and showed that the conjugation site affects the PEG chain
      conformation and the overall molecular architecture of the subunit. Compared to
      the original design where the PEG chain is located in the middle of the 3-helix
      bundle, micelle kinetic stability was reduced when the PEG chain was attached
      near the N-terminus (t(1/2) = 35 h) but was enhanced when the PEG chain was
      attached near the C-terminus (t(1/2) = 80 h). Quantitative structural and kinetic
      analysis suggest that the kinetic stability was largely dictated by the combined
      effects of entropic repulsion associated with PEG chain conformation and the
      geometric packing of the trimeric subunits. The modular design approach coupled
      with a variety of well-defined protein stucture and functional polymers will
      significantly expand the utility of these materials as nanocarriers to meet
      current demands in nanomedine.

PMID- 25575166
TI  - Outcomes following surgical intervention for impending and gross instability
      caused by multiple myeloma in the spinal column.
AB  - OBJECT: Multiple myeloma is the most common primary tumor of the spine and is the
      most common primary malignant tumor of bone. Although spinal myeloma is
      classically a radiosensitive lesion, clinical or radiographic signs of
      instability merit surgical intervention. The authors present the epidemiology,
      surgical indications, and outcome data of a series of consecutive cases involving
      31 surgically treated patients with diagnoses of multiple myeloma and
      plasmacytoma of the spine (the largest such series reported to date). METHODS:
      Surgical instability was the criterion for operative intervention in this patient
      cohort. The Spinal Instability Neoplastic Score (SINS) was used to make this
      assessment of instability. The cases were analyzed using location of the lesion,
      spinal levels involved, Frankel score, adjuvant therapy, functional outcome, and
      patient survival. RESULTS: All patients undergoing surgical intervention were
      determined to have indeterminate or gross spinal column instability according to
      SINS criteria. The median survival was 78.9 months. No significant difference in
      survival was seen for patients with higher SINS scores or for older patients (>
      55 years). There was a statistically significant difference in survival benefit
      observed for patients receiving chemotherapy and radiation versus radiation alone
      as an adjuvant to surgery (p = 0.02). CONCLUSIONS: In this 10-year analysis, the
      authors report outcomes of surgical intervention for patients with indeterminate
      or gross spinal instability due to multiple myeloma and plasmacytoma of the spine
      with improved neurological function following surgery and low rates of
      instrumentation failure.

PMID- 25575167
TI  - Progressive restoration of spinal sagittal balance after surgical correction of
      lumbosacral spondylolisthesis before skeletal maturity.
AB  - OBJECT: Spinopelvic alignment is crucial in assessing an energy-efficient posture
      in both normal and disease states, such as high-displacement developmental
      spondylolisthesis (HDDS). The overall effect in patients with HDDS who have
      undergone local surgical correction of lumbosacral imbalance for the global
      correction of spinal balance remains unclear. This paper reports the progressive
      spontaneous improvement of global sagittal balance following surgical correction
      of lumbosacral imbalance in patients with HDDS. METHODS: The records of 15
      patients with HDDS who underwent surgery between 2005 and 2010 were reviewed. The
      treatment consisted of L4-sacrum reduction and fusion via a posterior approach,
      resulting in complete correction of lumbosacral kyphosis. Preoperative, 6-month
      postoperative, and final follow-up postoperative angular measurements were taken
      from full-spine lateral radiographs obtained with the patient in a standard
      standing position. Radiographic measurements included pelvic incidence, sacral
      slope, lumbar lordosis, and thoracic kyphosis. The degree of lumbosacral kyphosis
      was evaluated by the lumbosacral angle. Because of the small number of patients,
      nonparametric tests were considered for data analysis. RESULTS: Preoperative
      lumbosacral kyphosis and L-5 anterior slip were corrected by instrumentation.
      Transient neurological complications were noted in 5 patients. Statistical
      analysis showed a significant increase of thoracic kyphosis on 6-month
      postoperative and final follow-up radiographs (p < 0.001). A statistically
      significant decrease of lumbar lordosis was noted between preoperative and 6
      month control radiographs (p < 0.001) and between preoperative and final follow
      up radiographs (p < 0.001). CONCLUSIONS: Based on the authors' observations, this
      technique resulted in an effective reduction of L-5 anterior slip and significant
      reduction of lumbosacral kyphosis (from 69.8 degrees  to 105.13 degrees ). Due to
      complete reduction of lumbosacral kyphosis and anterior trunk displacement
      associated with L-5 anterior slipping, lumbar lordosis progressively decreased
      and thoracic kyphosis progressively increased postoperatively. Adjusting the
      sagittal trunk balance produced not only pelvic anteversion, but also reciprocal
      adjustment of lumbar lordosis and thoracic kyphosis, creating a satisfactory
      level of compensated global sagittal balance.

PMID- 25575168
TI  - Structure and percolation of one-patch spherocylinders.
AB  - When the volume fraction exceeds the threshold, the colloidal particles would
      form a spanning cluster to realize percolation, which is affected by the shape of
      the particles, interaction between particles, etc. In this paper, we use the
      Monte Carlo method to study the structure and percolation of a system of one
      patch spherocylinders which have been fabricated recently [Chaudhary et al., J.
      Am. Chem. Soc., 2012, 134, 12901]. With strong adsorption, one-patch
      spherocylinders self-assemble into multipods which further make contact with each
      other to form a percolation network at a high volume fraction, while the
      percolation network is inhibited by the local structures in a system of one-patch
      spheres. The main multipods are dipods when the patch angle equals pi/3, while
      they are tetrapods and pentapods when the patch angle equals 2pi/3. With
      enhancing the adsorption, the bigger the patch angle, the more the percolation
      threshold drops. The orientational order parameter, the distribution of the
      relative orientation between the nearest neighbors and the probabilities of a
      spherocylinder owning n adsorbing neighbors have been calculated to analyze the
      formation and transition of the structures. 

PMID- 25575170
TI  - Simultaneous quantitative determination of celecoxib and its two metabolites
      using liquid chromatography-tandem mass spectrometry in alternating polarity
      switching mode.
AB  - A simple and rapid quantitative analytical method for the simultaneous detection
      of celecoxib and its two main metabolites, hydroxycelecoxib (celecoxib-OH) and
      celecoxib carboxylic acid (celecoxib-COOH), in rat plasma using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) was developed. The plasma
      sample was prepared through simple protein precipitation, and the reconstitution
      solution (0.1% formic acid in 50% methanol) was optimized to achieve the best
      peak shape and recovery. The analytes were separated using an Atlantis T3 column
      (2.1 mm * 100 mm, 3 MUm), and the mobile phase was composed of 10 mM ammonium
      formate in either 5% acetonitrile or 95% acetonitrile. The detection of the
      analytes was performed in alternating polarity switching mode using electrospray
      ionization. As celecoxib-OH and celecoxib-COOH were slightly unstable following
      freeze-thaw cycles and long-term storage at -80 degrees C in stability tests,
      every analysis was carefully conducted with one-freeze thaw cycle and a short
      storage duration (<1 week). Acceptable accuracy (<15%) and precision (<15%) were
      obtained in intra- and inter-day validations. The method was successfully applied
      to the pharmacokinetic study of celecoxib, celecoxib-OH and celecoxib-COOH
      following the oral administration of celecoxib in rats at a dose of 10mg/kg.
      Comparing the related pharmacokinetic parameters of celecoxib and its
      metabolites, celecoxib was quickly metabolized into celecoxib-OH and subsequently
      converted to celecoxib-COOH in short intervals. The AUCs for the two metabolites
      were less than 10% of that for celecoxib, indicating that the rate of celecoxib
      metabolism was low.

PMID- 25575169
TI  - Automated hollow fiber microextraction based on two immiscible organic solvents
      for the extraction of two hormonal drugs.
AB  - In this research, a rapid efficient and automated instrument based on hollow
      fiber liquid-phase microextraction (HF-LPME) followed by high performance liquid
      chromatography (HPLC) with UV-vis detection was applied for the preconcentration
      and determination of two hormonal drugs (megestrol acetate and levonorgestrel) in
      water and urinary samples. n-Dodecane was used as the supported liquid membrane
      (SLM) and methanol was used as the acceptor phase in the hollow fiber lumen. The
      effects of different parameters such as fiber length, extraction time, stirring
      rate, and ionic strength on the extraction efficiency were investigated using
      modified simplex and central composite design as the screening and optimization
      methods, respectively. The composition effect of SLM and type of acceptor phase
      were optimized separately. For adjustment of the SLM composition,
      trioctylphosphine oxide (TOPO) was chosen. Under optimized condition, the
      calibration curves were linear (r(2)>0.997) in the range of 0.5-200 MUg L(-1).
      LOD for both of the drugs were 0.25 MUg L(-1). The applicability of this
      technique was examined by analyzing drugs in water and urine samples. The
      relative recoveries of the drugs were in the range of 86.2-102.3% that show the
      capability of the method for the determination of the drugs in various matrices.

PMID- 25575171
TI  - Determination of isobavachalcone in rat plasma by LC-MS/MS and its application to
      a pharmacokinetic study.
AB  - A simple and selective specific high-performance liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method for determination of isobavachalcone (IBC) in
      rat plasma was developed. Neobavaisoflavone was used as an internal standard
      (IS). After protein precipitation with acetonitrile (2:1, v/v), the analyte and
      IS were separated on a 2.6 MUm Kinetex C18 column (100 mm*2.1 mm i.d.,
      Phenomenex) by isocratic elution with acetonitrile:water (60:40, v/v) as the
      mobile phase at a flow rate of 0.2 mL/min. An electrospray ionization (ESI)
      source was applied and operated in the negative ion mode; multiple reactions
      monitoring (MRM) mode was used for quantification, and the target fragment ions
      m/z 323.0->118.9 for IBC and m/z 321.1->265.0 for the IS were chosen. Good
      linearity was observed in the concentration range of 3.79-484.5 ng/mL for IBC in
      rat plasma. The recovery of IBC in plasma was in the range of 81.2-89.8%. Intra
      day and inter-day precision were both lower than 10%. This method was suitable
      for pharmacokinetic studies after oral administration of 80 mg/kg IBC in rats. We
      also obtained pharmacokinetic parameters and concentration-time profiles for IBC
      after oral administration of IBC in rats.

PMID- 25575172
TI  - Metabolite profiling for the identification of altered metabolic pathways in
      Alzheimer's disease.
AB  - Gas chromatography coupled to mass spectrometry is the most frequent tool for
      metabolomic profiling of low molecular weight metabolites. Its suitability in
      health survey is beyond doubt, given that primary metabolites involved in central
      pathways of metabolism are usually altered in diseases. The objective of this
      work is to investigate metabolic differences in serum between Alzheimer's disease
      patients and healthy controls in order to elucidate pathological mechanisms
      underlying to disease. Alterations in levels of 23 metabolites were detected,
      including increased lactic acid, alpha-ketoglutarate, isocitric acid, glucose,
      oleic acid, adenosine and cholesterol, as well as decreased urea, valine,
      aspartic acid, pyroglutamate, glutamine, phenylalanine, asparagine, ornithine,
      pipecolic acid, histidine, tyrosine, palmitic and uric acid, tryptophan, stearic
      acid and cystine. Metabolic pathway analysis revealed the involvement of multiple
      affected pathways, such as energy deficiencies, oxidative stress, hyperammonemia,
      and others. Moreover, it is noteworthy that some of these compounds have not been
      previously described in AD research, such as alpha-ketoglutarate, isocitrate
      pipecolic acid, pyroglutamate and adenosine, confirming the potential of this
      metabolomic approach in the search of novel potential markers for early detection
      of Alzheimer's disease. 

PMID- 25575173
TI  - Development and validation of a HPLC-MS/MS method for the determination of
      phytolaccagenin in rat plasma and application to a pharmacokinetic study.
AB  - Radix Phytolaccae (the dried root of Phytolacca acinosa Roxb. or Phytolacca
      americana L.) is widely used in East Asian countries for the treatment of
      inflammation-related diseases. The active component of Radix Phtolaccae is
      Phytolcaccagenin a triterpenoid saponin. Phytolcaccagenin has anti-inflammatory
      activities that exceed those of Esculentoside A and its derivatives regarding
      suppression of LPS-induced inflammation, and has a lower toxicity profile with
      less hemolysis. To date, no information is available about analytical method and
      pharmacokinetic studies of phytolaccagenin. To explore PK profile of this
      compound, a HPLC-MS/MS assay of phytolaccagenin in rat plasma was developed and
      validated. The method was fully validated according to FDA Guidance for industry.
      The detection was performed by a triple-quadrupole tandem mass spectrometer with
      multiple reactions monitoring (MRM) in positive ion mode via electrospray
      ionization. The monitored transitions were m/z 533.2>515.3 for Phytolcaccagenin,
      and 491.2>473.2 for I.S. The analysis was performed on a Symmetry C18 column (4.6
      mm * 50 mm, 3.5 MUm) using gradient elution with the mobile phase consisting of
      acetonitrile and 0.1% formic acid water at a flow rate of 1 ml/min with a 1:1
      splitter ratio. The method was validated with a LLOQ of 20 ng/ml and an ULOQ of
      1000 ng/ml. The response versus concentration data were fitted with 1/x weighting
      and the correlation coefficient (r) were greater than 0.999. The average matrix
      effect and the average extraction recovery were acceptable. This validation in
      rat plasma demonstrated that phytolaccagenin was stable for 30 days when stored
      below -20 degrees C, for 6h at room temperature (RT, 22 degrees C), for 12 h at
      RT for prepared control samples in auto-sampler vials, and during three
      successive freeze/thaw cycles results at -20 degrees C. The validated method has
      been successfully applied to an intravenous bolus pharmacokinetic study of
      phytolaccagenin in male Sprague-Dawley rats (10 mg/kg, i.v.). Blood samples taken
      from 0 to 24h after injection were collected, and data analyzed with WinNonlin.
      The half-life and clearance were 1.4+/-0.9 h and 2.1+/-1.1 L/h/kg, respectively.

PMID- 25575174
TI  - Integrated evaluation of malonyl ginsenosides, amino acids and polysaccharides in
      fresh and processed ginseng.
AB  - Many analytical methods have been developed to characterize ginsenosides in
      ginseng. Relatively less attention has been paid to the malonyl ginsenosides,
      amino acids and polysaccharides in various processing ginsengs. In this study,
      malonyl ginsenosides were characterized by LC-Q-TOF/MS. In positive mode, the
      most abundant ions at m/z 425.38 were observed corresponding to the
      protopanoxadiol-type ginsenosides. A rich diagnostic ion at 835.48 was shown
      representing the malonyl ginsenosides with at least two glucosides. Twelve
      malonyl ginsenosides were rapidly screened using 835.48-835.49 to restructure ion
      chromatograms. In negative mode, besides the high deprotonated ion, a neutral
      loss of 44 Da (CO2) was found. High-energy collision-induced dissociation at 50 V
      produced the most abundant product ion [M-H-malonyl](-) by a neutral loss of 86
      Da. Determination of 17 common amino acids was performed on an automatic amino
      acid analyzer. Arginine, glutamic acid, and aspartic acid were abundant. The
      contents of amino acids were 9.1% in fresh ginseng and 3.1% in black ginseng.
      Phenol-sulfuric acid method was applied to analysis of polysaccharides. The
      contents of polysaccharides were 29.1% in fresh ginseng and 11.1% in black
      ginseng. The optimal growth age for the accumulation of constituents was supposed
      to be 5-6 years. In conclusion, the contents of malonyl ginsenosides, amino
      acids, and polysaccharides, based on decreasing order, ranked as follows: fresh
      ginseng>frozen ginseng>white ginseng>stoved ginseng>red ginseng>black ginseng.
      Processing should be paid more attention for the quality control of ginseng
      products.

PMID- 25575175
TI  - Development and validation of an HPTLC method for apigenin 7-O-glucoside in
      chamomile flowers and its application for fingerprint discrimination of chamomile
      like materials.
AB  - Brewed tea of chamomile flowers (Matricaria recutita L.) (Asteraceae) has been
      extensively consumed for centuries due to either its pleasant taste or medicinal
      purposes. On the other hand, the major problem is difficulty in distinguishing
      the genuine specimen when supplying chamomile through nature-picking.
      Consequently flowers of other Asteraceae members resembling to chamomile in
      appearance may frequently be practiced by lay people or marketed in spice shops
      or bazaars. Evidently detection of such adulterations plays a vital role in terms
      of public health to avoid risk of toxicity (i.e. pyrazolidin alkaloids) and
      ineffective treatments (lack or insufficient concentration of the active
      constituents). This work presents either development and validation of a high
      performance thin-layer chromatographic (HPTLC) method for apigenin 7-O-glucoside
      which is one of the active markers in chamomile flowers or its application for
      the fingerprint discrimination of chamomile-like materials i.e. Anthemis spp.,
      Bellis spp., Chrysanthemum sp. and Tanacetum sp. gathered by local people
      assuming as chamomile. Separation was performed on the silica gel 60 NH2 F254s
      HPTLC plates using the developing solvent system of ethyl acetate-formic acid
      acetic acid-water (30:1.5:1.5:3, v/v/v/v). The proposed HPTLC method may also be
      a leading guide for the quality assessment of chamomile tea products on the
      market.

PMID- 25575177
TI  - The temperature dependent photoswitching of a classic diarylethene monitored by
      in situ X-ray diffraction.
AB  - Organic photochromic molecules including diarylethenes are of particular interest
      for their numerous potential applications including high-density optical data
      storage and light-activated switches. In this report, we examined the temperature
      dependence of the light-drive photocyclization reaction in a classic
      diarylethene. The steady-state populations were monitored spectroscopically and
      by temperature dependent in situ photocrystallography, the latter being the first
      reported example of this technique. The observed decrease in the steady-state
      population with decreasing temperature suggests this classic diarylethene
      possesses an excited-state potential energy surface topology similar to
      previously reported "inverted" diarylethenes. 

PMID- 25575176
TI  - Three-dimensional ultrasound molecular imaging of angiogenesis in colon cancer
      using a clinical matrix array ultrasound transducer.
AB  - OBJECTIVES: We sought to assess the feasibility and reproducibility of 3
      dimensional ultrasound molecular imaging (USMI) of vascular endothelial growth
      factor receptor 2 (VEGFR2) expression in tumor angiogenesis using a clinical
      matrix array transducer and a clinical grade VEGFR2-targeted contrast agent in a
      murine model of human colon cancer. MATERIALS AND METHODS: Animal studies were
      approved by the Institutional Administrative Panel on Laboratory Animal Care.
      Mice with human colon cancer xenografts (n = 33) were imaged with a clinical
      ultrasound system and transducer (Philips iU22; X6-1) after intravenous injection
      of either clinical grade VEGFR2-targeted microbubbles or nontargeted control
      microbubbles. Nineteen mice were scanned twice to assess imaging reproducibility.
      Fourteen mice were scanned both before and 24 hours after treatment with either
      bevacizumab (n = 7) or saline only (n = 7). Three-dimensional USMI data sets were
      retrospectively reconstructed into multiple consecutive 1-mm-thick USMI data sets
      to simulate 2-dimensional imaging. Vascular VEGFR2 expression was assessed ex
      vivo using immunofluorescence. RESULTS: Three-dimensional USMI was highly
      reproducible using both VEGFR2-targeted microbubbles and nontargeted control
      microbubbles (intraclass correlation coefficient, 0.83). The VEGFR2-targeted USMI
      signal significantly (P = 0.02) decreased by 57% after antiangiogenic treatment
      compared with the control group, which correlated well with ex vivo VEGFR2
      expression on immunofluorescence (rho = 0.93, P = 0.003). If only central 1-mm
      tumor planes were analyzed to assess antiangiogenic treatment response, the USMI
      signal change was significantly (P = 0.006) overestimated by an average of 27%
      (range, 2%-73%) compared with 3-dimensional USMI. CONCLUSIONS: Three-dimensional
      USMI is feasible and highly reproducible and allows accurate assessment and
      monitoring of VEGFR2 expression in tumor angiogenesis in a murine model of human
      colon cancer.

PMID- 25575178
TI  - Diagnostic disparity of previous and revised American Thoracic Society guidelines
      for idiopathic pulmonary fibrosis.
AB  - BACKGROUND: A revised guideline for the diagnosis of idiopathic pulmonary
      fibrosis (IPF) was formulated by the American Thoracic Society (ATS) in 2011 to
      improve disease diagnosis and provide a simplified algorithm for clinicians. The
      impact of these revisions on patient classification, however, remain unclear.
      OBJECTIVE: To examine the concordance between diagnostic guidelines to understand
      how revisions impact patient classification. METHODS: A cohort of 54 patients
      with either suspected IPF or a working diagnosis of IPF was evaluated in a
      retrospective chart review, in which patient data were examined according to
      previous and revised ATS guidelines. Patient characteristics influencing the
      fulfillment of diagnostic criteria were compared using one-way ANOVA and chi(2)
      tests. RESULTS: Revised and previous guideline criteria for IPF were met in 78%
      and 83% of patients, respectively. Revised guidelines modified a classification
      based on previous guidelines in 28% of cases. Fifteen percent of patients meeting
      previous ATS guidelines failed to meet revised criteria due to a lack of
      honeycombing on high-resolution computed tomography and the absence of a surgical
      lung biopsy. Patients failing to meet previous and revised diagnostic criteria
      for IPF were younger. CONCLUSION: The revised guidelines for the diagnosis of IPF
      classify a substantial proportion of patients differently than the previous
      guidelines.

PMID- 25575179
TI  - Structure of a low-population intermediate state in the release of an enzyme
      product.
AB  - Enzymes can increase the rate of biomolecular reactions by several orders of
      magnitude. Although the steps of substrate capture and product release are
      essential in the enzymatic process, complete atomic-level descriptions of these
      steps are difficult to obtain because of the transient nature of the intermediate
      conformations, which makes them largely inaccessible to standard structure
      determination methods. We describe here the determination of the structure of a
      low-population intermediate in the product release process by human lysozyme
      through a combination of NMR spectroscopy and molecular dynamics simulations. We
      validate this structure by rationally designing two mutations, the first
      engineered to destabilise the intermediate and the second to stabilise it, thus
      slowing down or speeding up, respectively, product release. These results
      illustrate how product release by an enzyme can be facilitated by the presence of
      a metastable intermediate with transient weak interactions between the enzyme and
      product. 

PMID- 25575181
TI  - Exploring lysine riboswitch for metabolic flux control and improvement of L
      lysine synthesis in Corynebacterium glutamicum.
AB  - Riboswitch, a regulatory part of an mRNA molecule that can specifically bind a
      metabolite and regulate gene expression, is attractive for engineering biological
      systems, especially for the control of metabolic fluxes in industrial
      microorganisms. Here, we demonstrate the use of lysine riboswitch and
      intracellular l-lysine as a signal to control the competing but essential
      metabolic by-pathways of lysine biosynthesis. To this end, we first examined the
      natural lysine riboswitches of Eschericia coli (ECRS) and Bacillus subtilis
      (BSRS) to control the expression of citrate synthase (gltA) and thus the
      metabolic flux in the tricarboxylic acid (TCA) cycle in E. coli. ECRS and BSRS
      were then successfully used to control the gltA gene and TCA cycle activity in a
      lysine producing strain Corynebacterium glutamicum LP917, respectively. Compared
      with the strain LP917, the growth of both lysine riboswitch-gltA mutants was
      slower, suggesting a reduced TCA cycle activity. The lysine production was 63%
      higher in the mutant ECRS-gltA and 38% higher in the mutant BSRS-gltA, indicating
      a higher metabolic flux into the lysine synthesis pathway. This is the first
      report on using an amino acid riboswitch for improvement of lysine biosynthesis.
      The lysine riboswitches can be easily adapted to dynamically control other
      essential but competing metabolic pathways or even be engineered as an "on
      switch" to enhance the metabolic fluxes of desired metabolic pathways. 

PMID- 25575182
TI  - Laser treatment of Ag@ZnO nanorods as long-life-span SERS surfaces.
AB  - UV nanosecond laser pulses have been used to produce a unique surface
      nanostructuration of Ag@ZnO supported nanorods (NRs). The NRs were fabricated by
      plasma enhanced chemical vapor deposition (PECVD) at low temperature applying a
      silver layer as promoter. The irradiation of these structures with single
      nanosecond pulses of an ArF laser produces the melting and reshaping of the end
      of the NRs that aggregate in the form of bundles terminated by melted ZnO
      spherical particles. Well-defined silver nanoparticles (NPs), formed by phase
      separation at the surface of these melted ZnO particles, give rise to a broad
      plasmonic response consistent with their anisotropic shape. Surface enhanced
      Raman scattering (SERS) in the as-prepared Ag@ZnO NRs arrays was proved by using
      a Rhodamine 6G (Rh6G) chromophore as standard analyte. The surface modifications
      induced by laser treatment improve the stability of this system as SERS substrate
      while preserving its activity. 

PMID- 25575180
TI  - Bioengineered human myobundles mimic clinical responses of skeletal muscle to
      drugs.
AB  - Existing in vitro models of human skeletal muscle cannot recapitulate the
      organization and function of native muscle, limiting their use in physiological
      and pharmacological studies. Here, we demonstrate engineering of electrically and
      chemically responsive, contractile human muscle tissues ('myobundles') using
      primary myogenic cells. These biomimetic constructs exhibit aligned architecture,
      multinucleated and striated myofibers, and a Pax7(+) cell pool. They contract
      spontaneously and respond to electrical stimuli with twitch and tetanic
      contractions. Positive correlation between contractile force and GCaMP6-reported
      calcium responses enables non-invasive tracking of myobundle function and drug
      response. During culture, myobundles maintain functional acetylcholine receptors
      and structurally and functionally mature, evidenced by increased myofiber
      diameter and improved calcium handling and contractile strength. In response to
      diversely acting drugs, myobundles undergo dose-dependent hypertrophy or toxic
      myopathy similar to clinical outcomes. Human myobundles provide an enabling
      platform for predictive drug and toxicology screening and development of novel
      therapeutics for muscle-related disorders. 

PMID- 25575183
TI  - Iron-catalyzed directed C2-alkylation and alkenylation of indole with vinylarenes
      and alkynes.
AB  - An iron-N-heterocyclic carbene catalyst generated from an iron(III) salt, an
      imidazolinium salt, and a Grignard reagent promotes alkylation and alkenylation
      reactions at the indole C2-position with vinylarenes and internal alkynes,
      respectively, via imine-directed C-H activation. The former reaction affords 1,1
      diarylalkane derivatives with exclusive regioselectivity. Deuterium-labeling
      experiments suggest that these reactions involve oxidative addition of the C-H
      bond to the iron center, insertion of the unsaturated bond into the Fe-H bond,
      and C-C reductive elimination. 

PMID- 25575184
TI  - A study of the sink effect by blood vessels in radiofrequency ablation.
AB  - The objective of the current work was to study the sink effect in radiofrequency
      ablation (RFA) caused by a blood vessel located close to an electrode in a two
      compartment numerical model, consisting of a spherical tumor embedded in healthy
      liver tissue. Several blood vessels of different sizes were studied at different
      distances from the electrode. It was found that when a straight blood vessel,
      cylindrical in shape, is located parallel to the electrode, the minimum distance
      for a drop of only 10% in the isothermal treatment volume above 50 degrees C,
      compared to the model without the blood vessel, varies from 4.49 mm (for a vessel
      of 2mm in diameter) to 20.02 mm (for a vessel 20mm in diameter). The results can
      be used as a guideline to clinical practitioners, in order to quickly assess the
      potential impact of existing blood vessels on the resulting treatment volume.

PMID- 25575185
TI  - Mathematical model in left ventricle segmentation.
AB  - In this paper a parametric model of the left ventricle is presented. Its task is
      to estimate the myocardium shape on those slices, on which the segmentation
      algorithm has outlined the structure incorrectly. The aim of using the model on
      improperly segmented slices is to improve the accuracy of computing cardiac
      hemodynamic parameters and the heart mass. The proposed model works with any
      segmentation algorithm. The usefulness of the model is the largest while
      determining the myocardium at end-systole and calculating the heart mass. In case
      of the segmentation algorithm applied in this study, the error decreased from
      clinically unacceptable to acceptable after using the presented model. 

PMID- 25575186
TI  - Grain Nutrient Composition of Maize (Zea mays L.) Drought-Tolerant Populations.
AB  - A total of 13 maize populations from the drought-tolerant mini core collection
      from Maize Research Institute gene bank were evaluated for oil, protein, and
      tryptophan contents, fatty acid (FA) composition, and kernel characteristics. All
      accessions are high oil (5.8-7.9%) and protein (10.58-12.45%) genotypes. Most of
      the accessions showed high contents of tryptophan (0.070-0.081%) and saturated
      (12.65-17.91%) and monounsaturated (24.19-45.52%) FAs. Significant positive
      correlations were found between oil and protein and between oil and tryptophan
      contents (p < 0.01). Correlations between oil and principal FA were non
      significant. Several accessions showed multiple nutritional advantages. For
      example, IP6428 had high oil (7.3%), tryptophan (0.081%), and saturated FA
      (17.9%) contents. Moreover, a positive correlation (p < 0.01) between palmitic
      (13.68%) and oleic (34.74%) acids enables the use of IP6428 for developing lines
      high in these FAs. Because drought-tolerant accessions were selected in both
      subtropical and temperate zones, they could be used for breeding value-added
      maize adapted to both environments.

PMID- 25575187
TI  - Anatomic dorsal and volar radioulnar ligament reconstruction with Mersilene
      augmentation for distal radioulnar joint instability.
AB  - Instability of the distal ulna is a fairly common problem after acute distal
      radius fracture (DRF), distal radius malunion, triangular fibrocartilage complex
      injury, and a host of other types of trauma. We present a new anatomic technique
      to stabilize the distal ulna with a tendon graft augmented with Mersilene tape,
      which has been used primarily to treat unidirectional (dorsal or volar)
      instability, but could be used for global instability as well. Of the 12 patients
      who underwent this procedure, 9 had stability fully restored and the remaining 3
      had only mild instability after surgery. The procedure is an effective treatment
      for distal radioulnar joint instability and we believe that this surgical
      technique will be a valuable adjunct to the existing described procedures for
      hand surgeons. We present a retrospective single-surgeon case series with outcome
      measures. 

PMID- 25575188
TI  - The use of computer-aided design and 3-dimensional models in the treatment of
      forearm malunions in children.
AB  - Computer-aided design has several orthopedic applications. In this article we
      propose the use of computer-aided design to address the problem of forearm
      malunions in children. Traditional methods of planning forearm osteotomies
      utilize 2-dimensional radiographs, however, this is not a reliable method to
      address rotational deformities. Our method involves collaboration with clinical
      engineers at Materialise (Leuven, Belgium) to produce patient-specific cutting
      jigs using preoperative computed tomographic scans and 3-dimensional printing
      technology. This method allows for precise planning of complex and multiple
      osteotomies while decreasing the need for intraoperative decision making. Our
      initial results with this technique demonstrate improvements in forearm rotation
      and distal radioulnar joint stability. 

PMID- 25575189
TI  - The follow-up of trapeziometacarpal arthrodesis using V-shaped osteotomy for
      osteoarthritis of the first carpometacarpal joint.
AB  - INTRODUCTION: Osteoarthritis of the trapeziometacarpal joint, also known as the
      thumb carpometacarpal joint, is one of the most common anatomic sites of
      arthritis in the human body. Many surgical techniques to address this problem
      have been developed; including, trapeziectomy with or without ligament
      reconstruction tendon interposition, implant arthroplasty, and arthrodesis. No
      methods have yet proven superior to the others, and each has associated
      limitations and complications. The primary complication found in the literature
      after arthrodesis of the trapeziometacarpal joint is nonunion; with a reported
      incidence in the literature as 13% (8% to 39%). METHODS: In 2010, a new surgical
      technique for this procedure was published by Wolff and Duerinckx in Techniques
      in Hand Surgery. In summary, a V-shaped osteotomy is made at the base of the
      first metacarpal and, together with a matching osteotomy of the trapezium,
      creates a more stable fusion site. Our current research looks at a minimum of 2
      year follow-up of patients treated with this technique between 2004 and 2012.
      RESULTS: Twenty-one patients, including 3 who had bilateral procedures, have
      participated in the study. The average age is 62.6 years (range, 51 to 76 y) with
      an average follow-up of 4.6 years (range, 2 to 8 y). Sixteen are female and 5 are
      male, with a variety of occupations. In these patients, the Quick DASH score
      improved 51% (49.8 to 24.2; P=0.0006), and the Quick DASH Work score improved 56%
      (52.8 to 23.2; P=0.0035). Nineteen of 21 patients said that they wound have the
      procedure again. Range of motion and strength of the operated versus nonoperated
      thumbs were compared and showed very similar capabilities. Seventy-five percent
      (18 of 24) were able to lay their hand flat. There were 4 fibrous unions,
      resulting in an 83% complete fusion rate. There were no infections or
      reoperations for nonunion. CONCLUSION: The data suggest that this procedure is a
      highly successful, pain-relieving, strength-preserving, reproducible arthrodesis
      with a nonunion rate similar to that of the published literature.

PMID- 25575190
TI  - Rational design of an efficient, genetically encodable, protein-encased singlet
      oxygen photosensitizer.
AB  - Singlet oxygen, O(2)(a(1)Delta(g)), plays a key role in many processes of cell
      signaling. Limitations in mechanistic studies of such processes are generally
      associated with the difficulty of controlling the amount and location of
      O(2)(a(1)Delta(g)) production in or on a cell. As such, there is great need for a
      system that (a) selectively produces O(2)(a(1)Delta(g)) in appreciable and
      accurately quantifiable yields and (b) can be localized in a specific place at
      the suborganelle level. A genetically encodable, protein-encased photosensitizer
      is one way to achieve this goal. Through a systematic and rational approach
      involving mutations to a LOV2 protein that binds the chromophore flavin
      mononucleotide (FMN), we have developed a promising photosensitizer that
      overcomes many of the problems that affect related systems currently in use.
      Specifically, by decreasing the extent of hydrogen bonding between FMN and a
      specific amino acid residue in the local protein environment, we decrease the
      susceptibility of FMN to undesired photoinitiated electron-transfer reactions
      that kinetically compete with O(2)(a(1)Delta(g)) production. As a consequence,
      our protein-encased FMN system produces O(2)(a(1)Delta(g)) with the uniquely
      large quantum efficiency of 0.25 +/- 0.03. We have also quantified other key
      photophysical parameters that characterize this sensitizer system, including
      unprecedented H(2)O/D(2)O solvent isotope effects on the O(2)(a(1)Delta(g))
      formation kinetics and yields. As such, our results facilitate future systematic
      developments in this field.

PMID- 25575191
TI  - Child-directed speech: An examination of frequency and reliability in spontaneous
      language samples.
AB  - Little research exists regarding language reliability, meaning that it is unknown
      to what degree language samples represent an individual's typical linguistic
      production. While few studies exist regarding child language reliability, fewer
      exist for adults. This study uses a test-retest procedure to examine frequency
      and reliability of morphosyntactic production in the language of 17 mothers
      interacting with their children. To examine reliability of different sample
      lengths, counts and reliability are calculated at 50, 100, 150 and 200
      utterances. Results are compared to those of children (2;6-3;6) involved in a
      larger study and reported in previous work. Results show that (1) frequency
      counts were higher for adults than children, (2) reliability of most elements was
      markedly lower in adult language, and (3) relative frequency of items in the
      child language samples mirrored those in adult samples.

PMID- 25575192
TI  - Pulsed Light Treatment of Different Food Types with a Special Focus on Meat: A
      Critical Review.
AB  - Today, the increasing demand for minimally processed foods that are at the same
      moment nutritious, organoleptically satisfactory, and free from microbial hazards
      challenges the research and development to establish alternative methods to
      reduce the level of bacterial contamination. As one of the recent emerging
      nonthermal methods, pulsed light (PL) constitutes a technology for the fast,
      mild, and residue-free surface decontamination of food and food contact materials
      in the processing environment. Via high frequency, high intensity pulses of broad
      spectrum light rich in the UV fraction, viable cells as well as spores are
      inactivated in a nonselective multi-target process that rapidly overwhelms cell
      functions and subsequently leads to cell death. This review provides specific
      information on the technology of pulsed light and its suitability for unpackaged
      and packaged meat and meat products as well as food contact materials like
      production surfaces, cutting tools, and packaging materials. The advantages,
      limitations, risks, and essential process criteria to work efficiently are
      illustrated and discussed with relation to implementation on industrial level and
      future aspects. Other issues addressed by this paper are the need to take care of
      the associated parameters such as alteration of the product and utilized
      packaging material to satisfy consumers and other stakeholders. 

PMID- 25575193
TI  - Highly selective adsorption of ethylene over ethane in a MOF featuring the
      combination of open metal site and pi-complexation.
AB  - The introduction of the combination of open metal site (OMS) and pi-complexation
      into MOF has led to very high ethylene-ethane adsorption selectivity at 318 K, as
      illustrated in the context of MIL-101-Cr-SO3Ag. The interactions with ethylene
      from both OMS and pi-complexation in MIL-101-Cr-SO3Ag have been investigated by
      in situ IR spectroscopic studies and computational calculations, which suggest
      that pi-complexation contributes dominantly to the high ethylene-ethane
      adsorption selectivity. 

PMID- 25575194
TI  - Evaluation of Cytotoxicity of Dentin Desensitizing Products.
AB  - OBJECTIVES: To evaluate the cytotoxic effects of the dentin desensitizing
      products (DDPs) used in the treatment of dentin hypersensitivity on cultured
      human gingival and pulpal fibroblast cells. METHODS AND MATERIALS: The cytotoxic
      effects of DDPs (Smart Protect, Systemp Desensitizer, Seal & Protect, Aqua-Prep
      F, Isodan, Gluma, BisBlock, D/Sense Crystal, UltraEZ, Colgate Sensitive Pro
      Relief, Topex, and Clinpro White Varnish) on cultured human gingival- and pulp
      derived fibroblast cells were evaluated using the 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) test (Serva, Heidelberg, Germany) under two
      different conditions. In the first test, different dilutions of the DDPs were
      directly applied onto cultured gingival fibroblast cells, and in the second test,
      the products were applied onto different-thickness dentin discs (0.5 and 1 mm)
      placed above cell culture medium, which contained pulp fibroblast cells. RESULTS:
      According to the cytotoxicity evaluations of gingival fibroblast cells, the
      cytotoxicity of all of the DDPs was very high at 50% concentrations (p<0.05).
      Colgate Sensitive Pro-Relief, Clinpro White Varnish, and Topex showed higher
      cytotoxicity than did the other products (p<0.05), decreasing with further
      dilutions, and these products were found to be less cytotoxic to both types of
      cells (p<0.05) than were the other products with further dilutions. The
      cytotoxicity to human gingival and pulpal fibroblast cells of Systemp
      Desensitizer, Aqua-Prep F, Isodan, and Gluma did not show any decrease with
      further dilutions, and these products were found to be more cytotoxic than the
      other products (p<0.05). CONCLUSIONS: According to the findings of this study,
      Colgate Sensitive Pro-Relief, Topex, and Clinpro White Varnish were less
      cytotoxic than the other DDPs used in this study.

PMID- 25575195
TI  - Surface Treatments that Demonstrate a Significant Positive Effect on the Shear
      Bond Strength of Repaired Resin-modified Glass Ionomer.
AB  - This study examined surface treatment options used to repair resin-modified glass
      ionomer (RMGI; GC Fuji II LC, GC America). Two hundred forty specimens were
      equally divided into four different water/temperature cycling environmental
      conditions. The conditions were 1) five-minute delay, 2) one-week delay with one
      thermocycle, 3) 500 thermocycles, and 4) 24-hour delay in a dry environment,
      followed by 500 thermocycles. Within each of the condition groups, the specimens
      were equally divided again into three different surface treatment groups with 20
      specimens in each. The treatment groups comprised A) sanding, B) sanding and acid
      etch, and C) sanding, acid etch, and dental bonding agent. Our results suggest
      that RMGI is extremely susceptible to the simultaneous exposure of temperature
      cycling and water during the first 24 hours. Our main results reflect that 1)
      during the first five minutes after the initial placement, the surface treatments
      made no difference in terms of the shear bond strength (NS); and 2) when we
      weakened the RMGI by exposing it to water and temperature cycling immediately
      after initial placement, each of the treatments (A<B<C) had a significant
      incremental increase in bond strength (p<0.05). As such, given that a RMGI is
      partially a composite resin, the surface treatment with a dental bonding agent
      did have a significant positive effect on the micromechanical bond strength of
      the repair. 

PMID- 25575196
TI  - Effectiveness of Different Mechanical Methods on Dentin Caries Removal: Micro-CT
      and Digital Image Evaluation.
AB  - PURPOSE: To determine the caries removal effectiveness (CRE) and minimal invasive
      potential (MIP) of caries excavation methods using digital imaging and
      microtomography analyses. METHODS: Twelve human molars with occlusal caries
      lesions in dentin were randomly divided into three groups (carbide bur,
      exacavator, and polymer bur). They were sectioned mesiodistally, and standardized
      digital and computed microtomography x-ray (micro-CT) images were taken from each
      section before and after caries excavation. On each image, initial carious dentin
      (IC), prepared cavity (PC), and residual caries (RC) were defined according to
      visual criteria using ImageJ software. CRE was determined based on the RC/IC
      ratio, whereas MIP was determined by the PC/IC ratio. Data were analyzed using
      one-way analysis of variance and Student t-test or with Kruskal-Wallis and
      Student-Newman-Keuls test. The level of significance was set at 0.05. RESULTS:
      For both digital image and micro-CT analysis, the carbide bur showed higher CRE
      values than the excavator (p=0.0063 and p=0.0263, respectively) and the polymer
      bur (p=0.0028 and p=0.0005, respectively). The latter two presented similar
      results (p>0.05). Regarding MIP, for the digital image analysis, the polymer bur
      was different from the carbide bur (p=0.0030) but was not different from that of
      the excavator (p=0.1240). For micro-CT analysis, the MIP values of all the groups
      were significantly different, and the polymer bur was the most conservative
      method (p<0.05). CONCLUSIONS: The carbide bur was the most effective method for
      caries removal but was not completely conservative. The polymer bur and excavator
      presented low invasive potential but were not able to remove all of the carious
      dentin.

PMID- 25575197
TI  - Effect of Desensitizing Agents on the Bond Strength of Mild and Strong Self
      etching Adhesives.
AB  - BACKGROUND: Desensitizing agents are used, almost as routine practice, in many
      adhesive restorative procedures. There is still debate as to their effect in
      dentin bonding, particularly with self-etching adhesives. The present study aimed
      to evaluate the effect of different desensitizing agents on the bond strength of
      mild and strong self-etching adhesive systems to dentin. MATERIALS AND METHODS:
      One hundred twenty recently extracted, noncarious human molars were used to
      obtain superficial dentin substrate for bonding. No desensitizer was used in the
      control groups. The experimental groups were pretreated with Gluma Desensitizer,
      MicroPrime B, and Dentin Desensitizer immediately prior to bonding with self
      etching adhesives Optibond XTR, Xeno IV, and iBond. A bonding jig was used to
      fabricate composite cylinders, which were stored for either 24 hours or three
      months, after which the shear bond strength (SBS) was evaluated using a notched
      edge testing device at a crosshead speed of 1 mm/min. Failure mode distribution
      was also evaluated at 24 hours and three months. A two-way analysis of variance,
      Tukey test, and Student t-test, with a significance level of p<0.05, were used
      for data analysis. RESULTS: At 24 hours, there was no significant difference in
      SBS when the same adhesive was used with any of the experimental desensitizing
      agents compared with the control group without desensitizer. However, at three
      months, Dentin Desensitizer bonded with Optibond XTR demonstrated significantly
      lower SBS (p<0.001), while Gluma bonded with iBond showed significantly higher
      SBS values (p=0.034) relative to their corresponding control group. Only
      MicroPrime B bonded with Xeno IV and iBond with no desensitizer demonstrated a
      significant reduction in SBS after three months (p=0.034 and p=0.002,
      respectively). The most prevalent type of failure was adhesive. CONCLUSION:
      Desensitizing agents can be used in combination with self-etching adhesives to
      control hypersensitivity without adversely affecting their bond strength to
      dentin.

PMID- 25575198
TI  - Reestablishing Biology, Function, and Esthetics for Fractured, Immature Incisors.
AB  - A seven-year-old boy with enamel-dentin fractures on both maxillary central
      incisors presented to the Piracicaba Dental School-UNICAMP seven days after the
      trauma. At the clinical evaluation, there were no clinical signs of pulp
      exposure, neither tooth was mobile, and both affected teeth presented a positive
      response to sensitivity tests and a negative response for percussion and
      palpation. The radiographic examination showed an undeveloped root and opened
      apex for both teeth. Indirect pulp capping was performed on the left maxillary
      central incisor, followed by a direct restoration. After one month, the patient
      complained of pain in the left central incisor, which responded negatively to
      sensitivity testing. Pulp revascularization was performed only on this tooth and
      was followed for 18 months. During this period, the left maxillary central
      incisor did not recover sensitivity, although radiographic examination showed
      apical closure, a slight increase in root length, and the formation of a
      mineralized barrier between the root canal and sealing material. The technique
      achieved its goal of restoring biological aspects, function, and esthetics of
      traumatized teeth when using this multidisciplinary approach. 

PMID- 25575199
TI  - Cytotoxic Effects of Hydrogen Peroxide on Human Gingival Fibroblasts In Vitro.
AB  - In-office bleaching is a popular treatment in modern esthetic dentistry. However,
      bleaching agents sometimes accidentally adhere to the gingiva and peripheral
      tissues, even when applied by well-trained dentists. This can lead to transient
      pain and whitish changes in the gingiva. Although these symptoms disappear within
      several hours, the effects of bleaching agents on gingiva have not been well
      described in the literature. The present study aimed to elucidate the cytotoxic
      effects of a bleaching agent on cultured human gingival fibroblasts (HGFs). We
      performed a comprehensive analysis of the toxic effects of in-office bleaching
      agents on gingiva using cultured HGFs and DNA microarray. Survival rates of HGFs
      decreased with increases in the concentration of hydrogen peroxide, which became
      significant at concentrations of 1.5 * 10(-3)% or higher at every time point.
      Concentrations lower than 1.5 * 10(-3)% did not affect survival rates of HGFs.
      Cytotoxicity of hydrogen peroxide was significantly weakened by the addition of
      vitamin E. Stimulation by in-office bleaching agents triggered the
      proinflammatory cytokine tumor necrosis factor (TNF)-alpha cascade in gingival
      fibroblasts. As the TNF-alpha cascade can be inhibited by vitamin E additives,
      treatment with vitamin E may protect gingival fibroblasts against the toxic
      effects of an in-office bleaching agent. The present results suggest that local
      administration of vitamin E to gingiva before in-office bleaching may be useful
      for preventing gingival irritation due to accidental adhesion of a bleaching
      agent. 

PMID- 25575200
TI  - Bonding of Adhesive Luting Agents to Caries-affected Dentin Induced by a
      Microcosm Biofilm Model.
AB  - OBJECTIVES: To evaluate the bond strength of adhesive luting agents applied to
      caries-affected dentin (CAD). METHODS: Thirty-six noncarious human third molars
      were abraded to expose an occlusal dentin surface. Caries lesions were induced in
      half of the samples using a microcosm biofilm model. Biofilm was cultivated under
      an anaerobic atmosphere for 14 days in a medium enriched with mucin. The same
      medium containing 1% sucrose was alternated for 4 hours per day. Cylinders of
      resin cement (RelyX ARC, RelyX U200, or BisCem) were built up over the dentin
      substrate and submitted to shear bond load. The samples were then longitudinally
      sectioned. The hardness and elastic modulus of dentin were measured at different
      depths from the occlusal surface. A three-dimensional finite element simulation
      was performed to analyze the residual stress distribution during the shear bond
      strength test. Bond strength data were analyzed by two-way analysis of variance
      (ANOVA) and hardness and elastic modulus by split-plot ANOVA. Multiple
      comparisons were performed with the SNK test (alpha=0.05). RESULTS: For all
      cements, the highest bond strengths were observed in sound dentin. Relyx ARC bond
      strength was similar to that of RelyX U200 for both substrates; BisCem had the
      lowest values. CAD had lower hardness (above a depth of 100 MUm) and elastic
      modulus (above a depth of 150 MUm) values than sound dentin. Stress distribution
      during the bond strength test was similar under all experimental conditions.
      CONCLUSION: Impairment of the mechanical properties of dentin promoted by carious
      lesions reduced the bond strength of adhesive luting agents.

PMID- 25575201
TI  - Enamel Bond Strength of New Universal Adhesive Bonding Agents.
AB  - PURPOSE: Universal bonding agents have been introduced for use as self-etch or
      etch-and-rinse adhesives depending on the dental substrate and clinician's
      preference. The purpose of this study was to evaluate the shear bond strength
      (SBS) of composite to enamel using universal adhesives compared to a self-etch
      adhesive when applied in self-etch and etch-and-rinse modes over time. METHODS
      AND MATERIALS: Extracted human third molars were used to create 120 enamel
      specimens. The specimens were ground flat and randomly divided into three groups:
      two universal adhesives and one self-etch adhesive. Each group was then
      subdivided, with half the specimens bonded in self-etch mode and half in etch-and
      rinse mode. The adhesives were applied as per manufacturers' instructions, and
      composite was bonded using a standardized mold and cured incrementally. The
      groups were further divided into two subgroups with 10 specimens each. One
      subgroup was stored for 24 hours and the second for six months in 37 degrees C
      distilled water and tested in shear. Failure mode was also determined for each
      specimen. RESULTS: A three-way analysis of variance (ANOVA) found a significant
      difference between groups based on bonding agent (p<0.001) and surface treatment
      (p<0.001) but not on time (p=0.943), with no significant interaction (p>0.05).
      Clearfil SE in etch-and-rinse and self-etch modes had more mixed fractures than
      either universal adhesive in either mode. CONCLUSIONS: Etching enamel
      significantly increased the SBS of composite to enamel. Clearfil SE had
      significantly greater bond strength to enamel than either universal adhesive,
      which were not significantly different from each other.

PMID- 25575202
TI  - Conservative Restoration of Worn Mandibular Anterior Teeth Combining Gingival
      Repositioning and a Template Matricing Technique.
AB  - Conservative resin composite restoration of worn mandibular anterior teeth may
      offer an alternative option to full-coverage restorations for the patient.
      Assessment of the occlusal condition is critical because alterations in occlusal
      vertical dimension may not always be possible. By exposing additional coronal
      tooth structure, periodontal crown-lengthening procedures can serve to increase
      clinical crown height when adequate attached gingival tissue is present and supra
      eruption has likely occurred. Fabrication of a custom template made from a
      diagnostic mock-up with proximal stainless steel matrices helps contribute to a
      predictable restorative result and improves chairside efficiency for the dental
      practice. By combining gingival crown lengthening, bonding of resin composite
      material, and selective occlusal adjustment; a short to medium-term, conservative
      option can be made available for the patient. 

PMID- 25575203
TI  - Maxillary and Mandibular Rehabilitation in the Esthetic Zone Using a Digital
      Impression Technique and CAD/CAM-fabricated Prostheses: A Multidisciplinary
      Clinical Report.
AB  - Interdisciplinary treatment planning is necessary in certain clinical situations
      to optimize esthetic treatment outcomes. Patients presenting with severe wear of
      their anterior teeth from iatrogenic influences pose a particularly difficult
      problem in terms of esthetic treatment planning. Collaboration of practitioners
      from the disciplines of orthodontics, periodontics, and restorative dentistry is
      essential for the treatment of patients with complex esthetic dental needs.
      Careful assessment of clinical situations and corresponding specialty
      consultations are of utmost importance to achieve more predictable and esthetic
      treatment outcomes. The purpose of this clinical case is to report to the
      readership a novel digital fabrication of computer-aided design/computer-aided
      manufacturing milled acrylic provisional restorations and final lithium
      disilicate definitive restorations after orthodontic and periodontal therapy with
      virtual master impressions, casts, and articulation. 

PMID- 25575205
TI  - Role and significance of extracellular polymeric substances from granular sludge
      for simultaneous removal of organic matter and ammonia nitrogen.
AB  - This study analyzed the organics and content of metal ions in extracellular
      polymeric substances (EPSs), tightly (TB-EPSs) and loosely (LB-EPSs) bound EPSs
      of granular sludge with simultaneous removal of organic matters and ammonia
      nitrogen, studied the dynamic variation of metal ions in EPSs from granular
      sludge with different particle sizes and the change of zeta potential before and
      after cation exchange resin (CER) treatment. Results showed, with particle size
      increasing, the protein content gradually increased, the content of
      polysaccharide basically unchanged; the content of Ca, Mg, K, Na and Zn also
      increased, whereas others did not show a consistent regularity. The existence of
      metal ions reduced zeta potential of EPSs. The existence of metal ions helped to
      the adhesion among granules, in order to form a granule with bigger particle
      size. 

PMID- 25575204
TI  - Effect of lipase addition on hydrolysis and biomethane production of Chinese food
      waste.
AB  - The lipase obtained from Aspergillums niger was applied to promote the hydrolysis
      of food waste for achieving high biomethane production. Two strategies of lipase
      additions were investigated. One (Group A) was to pre-treat food waste to pre
      decompose lipid to fatty acids before anaerobic digestion, and another one (Group
      B) was to add lipase to anaerobic digester directly to degrade lipid inside
      digester. The lipase was used at the concentrations of 0.1%, 0.5%, and 1.0%
      (w/v). The results showed that Group A achieved higher biomethane production, TS
      and VS reductions than those of Group B. At 0.5% lipase concentration, Group A
      obtained experimental biomethane yield of 500.1 mL/g VS(added), 4.97-26.50%
      higher than that of Group B. The maximum Bd of 73.8% was also achieved in Group
      A. Therefore, lipase pre-treatment strategy is recommended. This might provide
      one of alternatives for efficient biomethane production from food waste and
      mitigating environmental impact associated.

PMID- 25575206
TI  - Mimicking the Fenton reaction-induced wood decay by fungi for pretreatment of
      lignocellulose.
AB  - In this study, the Fenton reaction, which is naturally used by fungi for wood
      decay, was employed to pretreat rice straw and increase the enzymatic
      digestibility for the saccharification of lignocellulosic biomass. Using an
      optimized Fenton's reagent (FeCl3 and H2O2) for pretreatment, an enzymatic
      digestibility that was 93.2% of the theoretical glucose yield was obtained. This
      is the first report of the application of the Fenton reaction to lignocellulose
      pretreatment at a moderate temperature (i.e., 25 degrees C) and with a relatively
      high loading of biomass (i.e., 10% (w/v)). Substantial improvement in the process
      economics of cellulosic fuel and chemical production can be achieved by replacing
      the conventional pretreatment with this Fenton-mimicking process. 

PMID- 25575207
TI  - Use of wavelength-selective optical light filters for enhanced microalgal growth
      in different algal cultivation systems.
AB  - This work is to use thin film nano-materials as light filters to selectively
      transmit certain wavelengths from natural sunlight to algal culture. A red light
      filter (620-710 nm) and blue filter (450-495 nm) were evaluated. Algae were grown
      in flasks, flat panel reactors, and rotating algal biofilm (RAB) system. It was
      found that the light filters did not improve algal growth in flask cultures,
      probably due to the additional reflection of light by the glass wall of the
      flasks. However, the light filters significantly (P<0.05) improved biomass yield
      (13-34%) in flat panel reactors and biomass productivity (70-100%) in RAB system,
      depending on the growth mode and lighter filters. Such improvements may be due to
      the eliminating the ultra-violet (UV) damaging the cellular structure. The
      biomass compositions did not change significantly among different light-filter
      cultures (P>0.05). The research shows a great potential of using light filters to
      improve microalgal growth.

PMID- 25575208
TI  - The characteristics of TAG and EPA accumulation in Nannochloropsis oceanica IMET1
      under different nitrogen supply regimes.
AB  - The strategy of nitrogen limitation has been widely applied to enhance lipid
      production in microalgae. The changes of cellular composition, and the
      characteristics of triacylglycerol (TAG) and eicosapentaenoic acid (EPA)
      accumulation in Nannochloropsis oceanica IMET1 were investigated. The results
      revealed that after nitrogen limitation TAG rather than carbohydrate was the
      dominant carbon sink in N. oceanica IMET1. Different nitrogen supplementation
      strategies were applied in order to achieve high TAG and EPA productivity,
      respectively. Limited nitrogen was supplied to improve TAG production, and a
      maximum productivity of 29.44 mg L(-1) d(-1) was obtained, which was a 6.74-fold
      increase compared to nitrogen-depleted cultivation. The highest EPA productivity
      of 7.66 mg L(-1) d(-1) was achieved under nitrogen-replete cultivation, which is
      different from the condition for TAG maximum productivity because the EPA is in
      glycolipids and phospholipids mainly. The fatty acid composition analysis
      identified the source of acyl group in TAG accumulation.

PMID- 25575209
TI  - Enhanced hydrolysis of Macrocystis pyrifera by integrated hydroxyl radicals and
      hot water pretreatment.
AB  - Integrated hydroxyl radicals and hot water pretreatment (IHRHW) was employed in
      the bioconversion of the brown macroalgae Macrocystis pyrifera (M. pyrifera) in
      this study. The optimum experimental pretreatment condition (100 degrees C, 30
      min, 11.9 mM FeSO4) and the predicted optimum pretreatment condition (113.95
      degrees C, 29.1 min, 12.75 mM FeSO4) were identified using a central composite
      design method. All glucan and xylan were recovered as monosaccharides or
      polysaccharides without a fermentation inhibitor (e.g., hydroxymethyl furfural
      and furfural). The IHRHW-treated macroalgae digestibility reached 88.1% under the
      optimum experimental condition, whereas that under the predicted optimum
      condition reached 92.1%. The value was approximately threefold higher than those
      obtained with untreated M. pyrifera. Carbohydrate recovery and enzymatic
      hydrolysis can be significantly enhanced by the new economic hydroxyl radicals
      and hot water pretreatment.

PMID- 25575210
TI  - Advanced nitrogen removal from wastewater by combining anammox with partial
      denitrification.
AB  - The anammox (anaerobic ammonium oxidation) process has attracted much attention
      for its cost-saving. However, excess nitrate is usually produced which should be
      further treated. In this study, an innovative process combined anammox with
      partial denitrification (nitrate->nitrite) was proposed for advanced nitrogen
      removal in two sequencing batch reactors (SBRs). The nitrate produced in anammox
      SBR (ASBR) was fed into partial denitrification-SBR (DSBR), in which the nitrate
      was reduced to nitrite, and then removed by backflow of the nitrite to ASBR for
      secondary anammox process. Results showed that ~80% nitrate in the effluent of
      previous anammox was converted to nitrite in DSBR. And the maximum nitrogen
      removal efficiency (NRE) of 94.06% was obtained with total nitrogen (TN) in the
      effluent of 10.98 mg/L in average. It indicated that desired effluent quality
      could be achieved, and the advanced nitrogen removal performance was attributed
      to the successful achievement of partial denitrification.

PMID- 25575211
TI  - Biomass and pigments production in photosynthetic bacteria wastewater treatment:
      effects of light sources.
AB  - This study is aimed at enhancing biomass and pigments production together with
      pollution removal in photosynthetic bacteria (PSB) wastewater treatment via
      different light sources. Red, yellow, blue, white LED and incandescent lamp were
      used. Results showed different light sources had great effects on the PSB. PSB
      had the highest biomass production, COD removal and biomass yield with red LED.
      The corresponding biomass, COD removal and biomass yield reached 2580 mg/L, 88.6%
      and 0.49 mg-biomass/mg-COD-removal, respectively. The hydraulic retention time of
      wastewater treatment could be shortened to 72 h with red LED. Mechanism analysis
      showed higher ATP was produced with red LED than others. Light sources could
      significantly affect the pigments production. The pigments productions were
      greatly higher with LED than incandescent lamp. Yellow LED had the highest
      pigments production while red LED produced the highest
      carotenoid/bacteriochlorophyll ratio. Considering both efficiency and energy
      cost, red LED was the optimal light source.

PMID- 25575212
TI  - Minimization of nitrous oxide emission in a pilot-scale oxidation ditch:
      generation, spatial variation and microbial interpretation.
AB  - Nitrous oxide (N2O) emission from wastewater treatment plants (WWTPs) has
      received increasing attention. This paper presented how N2O emission was
      significantly reduced in a pilot-scale Carrousel oxidation ditch under reasonable
      nitrification and denitrification. N2O emission from the reactor was found as low
      as 0.027% of influent nitrogen, which was much less than that from other
      processes. Further measurements on spatial variation of N2O emission in the
      alternative aerobic/anoxic zones with help of a series of batch experiments
      demonstrated that about 90% of the emission was contributed by nitrifier
      denitrification (ND). Moreover, the taxonomic analysis based on high through-put
      16S rRNA gene sequencing revealed that the high abundance of denitrifying
      bacteria and nitrite-oxidizing bacteria (NOB) was responsible for low nitrite
      accumulations and consequent low N2O emissions. However, N2O generation would be
      greatly increased upon the normal operation being shocked by either ammonia
      overload or aeration failure of the oxidation ditch system. 

PMID- 25575213
TI  - Low-temperature vaterite-type LuBO3, a vacancy-stabilized phase synthesized at
      high temperature.
AB  - Low-temperature vaterite-type LuBO(3) (pi-LBO) was prepared by a solid-state
      reaction method at high temperature. The reasoning of the existence of vacancy
      stabilized pi-LBO was investigated for the first time using neutron diffraction
      patterns, Fourier transform infrared (FT-IR) spectra, and high-resolution
      transmission electron microscopy. The results clearly demonstrated that the B and
      O vacancies in pi-LBO came into being during the heating process. The existence
      of an open B(3)O(9) ring consisting of BO(3) and BO(4) units in pi-LBO due to the
      B and O vacancies was demonstrated by FT-IR. The vacuum ultraviolet-ultraviolet
      spectroscopic properties of pi-LBO were studied in detail. In addition, the
      luminescence mechanism of Ce(3+) in pi-LBO was put forward and discussed with
      that of calcite-type LuBO(3) (beta-LBO).

PMID- 25575215
TI  - Correction: Theoretical study and design of multifunctional phosphorescent
      platinum(ii) complexes containing triarylboron moieties for efficient OLED
      emitters.
AB  - Correction for 'Theoretical study and design of multifunctional phosphorescent
      platinum(ii) complexes containing triarylboron moieties for efficient OLED
      emitters' by Yong Wu et al., Phys. Chem. Chem. Phys., 2015, DOI: . 

PMID- 25575214
TI  - The evolution of cyclopropenium ions into functional polyelectrolytes.
AB  - Versatile polyelectrolytes with tunable physical properties have the potential to
      be transformative in applications such as energy storage, fuel cells and various
      electronic devices. Among the types of materials available for these
      applications, nanostructured cationic block copolyelectrolytes offer mechanical
      integrity and well-defined conducting paths for ionic transport. To date, most
      cationic polyelectrolytes bear charge formally localized on heteroatoms and lack
      broad modularity to tune their physical properties. To overcome these challenges,
      we describe herein the development of a new class of functional polyelectrolytes
      based on the aromatic cyclopropenium ion. We demonstrate the facile synthesis of
      a series of polymers and nanoparticles based on monomeric cyclopropenium building
      blocks incorporating various functional groups that affect physical properties.
      The materials exhibit high ionic conductivity and thermal stability due to the
      nature of the cationic moieties, thus rendering this class of new materials as an
      attractive alternative to develop ion-conducting membranes.

PMID- 25575216
TI  - Comparison of the effects of lanthanum, cerium and praseodymium on rumen
      fermentation, nutrient digestion and plasma biochemical parameters in beef
      cattle.
AB  - The objectives of the trial were to compare the effects of supplementing rare
      earth elements (REE) lanthanum (La), cerium (Ce) and praseodymium (Pr) on rumen
      fermentation, nutrient digestion, methane (CH4) production, nitrogen (N) balance
      and plasma biochemical parameters in beef cattle. Four Simmental male cattle,
      aged 12 months, with initial average liveweight of 333 +/- 9 kg and fitted with
      rumen cannulas, were fed with a basal ration composed of concentrate mixture and
      maize silage. Animals received a basal ration without adding REE (Control) or
      three treatments, i.e. supplementing LaCl3, CeCl3 or PrCl3 at 204 mg/kg DM to the
      basal ration, respectively, which were allocated in a 4 * 4 Latin square design.
      Each experimental period lasted 15 d, consisting of 12 d for pre-treatment and
      three subsequent days for sampling. Results showed that all tested levels of REE
      tended to increase neutral detergent fibre digestibility (p = 0.064) and tended
      to decrease rumen CH4 production (p = 0.056). Supplementing LaCl3 and CeCl3
      decreased total N excretion and urinary N excretion, increased N retention (p <
      0.05), tended to increase total urinary purine derivatives (PD) (p = 0.053) and
      microbial N flow (p = 0.095), whereas supplementing PrCl3 did not affect N
      retention, urinary PD and microbial N flow. No differences were found in the
      effects of nutrient digestibility, CH4 production and plasma biochemical
      parameters among LaCl3, CeCl3 and PrCl3. Further trials using graded levels of
      LaCl3, CeCl3 and PrCl3 in a wide range are needed to obtain more pronounced
      results for comparing effects of La, Ce and Pr on rumen fermentation and nutrient
      digestion in beef cattle.

PMID- 25575218
TI  - Neural enhancement for independent living.

PMID- 25575219
TI  - Science-based neurorehabilitation: recommendations for neurorehabilitation from
      basic science.
AB  - Neuroscience has fundamentally changed the understanding of learning and memory
      within recent years. Here, the authors discuss a number of specific areas where
      they believe new understanding of the CNS from basic science is having a
      fundamental impact on neurorehabilitation and is leading to new therapeutic
      approaches. These areas have constituted a basis for development of some basic
      principles for neurorehabilitation: Optimal rehabilitation should involve (a)
      active (patient) participation in the training, (b) training that does not only
      involve many repetitions, but also continues to challenge the skill of the
      training person, (c) motivation and reward, (d) intensive training and practice
      over a long time, (e) careful organization of the training in relation to other
      activities, and (f) incorporation of other potentially beneficial parameters such
      as sleep and diet. It should in this relation also be pointed out that albeit
      neurorehabilitation may be predicted to have the most optimal effect early in
      life and as soon after injury as possible, there is no reason to believe that
      beneficial effects of training may not be obtained late in life or several years
      after injury.

PMID- 25575220
TI  - A fully automated, quantitative test of upper limb function.
AB  - The Rehabilitation Joystick for Computerized Exercise (ReJoyce, Rehabtronics
      Inc., Edmonton, Alberta, Canada), is a workstation on which participants exercise
      dexterous movement tasks in the guise of computer games. The system incorporates
      the ReJoyce Arm and Hand Function Test (RAHFT). Here the authors evaluate the
      RAHFT against the Action Research Arm Test (ARAT) and the Fugl-Meyer Assessment
      (FMA). All 3 tests were performed in 36 separate sessions in 13 tetraplegic
      individuals. Concurrent and criterion validities of the RAHFT were supported by a
      high level of correlation with the ARAT (r2 = .88). Regarding responsiveness, the
      effect size of the RAHFT at week 6 of 1 hr/day exercise training was 1.8.
      Regarding reliability, the mean test-retest difference in RAHFT baseline scores
      was 0.67% +/- 3.6%, which was not statistically significant. The RAHFT showed
      less ceiling effect than either ARAT or FMA. These data help validate the RAHFT
      as a quantitative, automated alternative to the ARAT and FMA. The RAHFT is the
      first comprehensive test of arm and dexterous hand function that does not depend
      on human judgment. It offers a standardized, quantitative outcome evaluation,
      which can be performed not only in the clinic, but also in the participant's
      home, administered by a remote therapist over the Internet.

PMID- 25575221
TI  - Does response inhibition have pre- and postdiagnostic utility in Parkinson's
      disease?
AB  - Parkinson's disease (Pd) is the second most prevalent degenerative neurological
      condition worldwide. Improving and sustaining quality of life is an important
      goal for Parkinson's patients. Key areas of focus to achieve this goal include
      earlier diagnosis and individualized treatment. In this review the authors
      discuss impulse control in Pd and examine how measures of impulse control from a
      response inhibition task may provide clinically useful information (a) within an
      objective test battery to aid earlier diagnosis of Pd and (b) in postdiagnostic
      Pd, to better identify individuals at risk of developing impulse control
      disorders with dopaminergic medication.

PMID- 25575222
TI  - Greater intermanual transfer in the elderly suggests age-related bilateral motor
      cortex activation is compensatory.
AB  - Hemispheric lateralization of movement control diminishes with age; whether this
      is compensatory or maladaptive is debated. The authors hypothesized that if
      compensatory, bilateral activation would lead to greater intermanual transfer in
      older subjects learning tasks that activate the cortex unilaterally in young
      adults. They studied 10 young and 14 older subjects, learning a unimanual
      visuomotor task comprising a feedforward phase, where there is unilateral
      cortical activation in young adults, and a feedback phase, which activates the
      cortex bilaterally in both age groups. Increased intermanual transfer was
      demonstrated in older subjects during feedforward learning, with no difference
      between groups during feedback learning. This finding is consistent with
      bilateral cortical activation being compensatory to maintain performance despite
      declining computational efficiency in neural networks.

PMID- 25575223
TI  - Practice effects in bimanual force control: does age matter?
AB  - The authors examined age-related differences in fine motor control during a
      bimanual coordination task. The task required the modulation of fingertip forces
      in the precision grip according to a visually presented sinusoidal antiphase
      pattern (force range 2-12 N; frequency 0.2 Hz). Thirty-four right-handed
      participants of three age groups (young, early middle-aged, and late middle-aged)
      practiced 30 trials of the task. Accuracy and variability of relative timing and
      relative forces at minima and maxima of the sine wave were analyzed for hand-hand
      and hand-stimulus couplings and compared between age groups. Analysis showed for
      relative timing and force weaker hand-hand than hand-stimulus coupling as well as
      lower accuracy and higher variability for minima as compared to maxima. Further,
      we analyzed practice effects by comparing the first and last trials and
      characterized the course of practice by detecting the transition of a steeper to
      a shallower acquisition slope for the different age groups. Late middle-aged
      participants demonstrated poorer performance than both other groups for all
      parameters. All groups improved performance to a similar amount. However, an age
      related difference in acquisition strategy is visible. Late middle-aged
      participants seemed to have focused on improvement of force amplitude, whereas
      young and early middle-aged focused on timing.

PMID- 25575224
TI  - The potential transformation of our species by neural enhancement.
AB  - Neural enhancement represents recovery of function that has been lost due to
      injury or disease pathology. Restoration of functional ability is the objective.
      For example, a neuroprosthetic to replace a forearm and hand lost to the ravages
      of war or industrial accident. However, the same basic constructs used for neural
      enhancement after injury could amplify abilities that are already in the natural
      normal range. That is, neural enhancement technologies to restore function and
      improve daily abilities for independent living could be used to improve so-called
      normal function to ultimate function. Approaching that functional level by use
      and integration of technology takes us toward the concept of a new species. This
      new subspecies--homo sapiens technologicus--is one that uses technology not just
      to assist but to change its own inherent biological function. The author uses
      examples from prosthetics and neuroprosthetics to address the issue of the
      limitations of constructs on the accepted range of human performance ability and
      aims to provide a cautionary view toward reflection on where our science may take
      the entire species.

PMID- 25575226
TI  - [Who invented it?].

PMID- 25575225
TI  - Association of depression and loneliness with specific cognitive performance in
      non-demented elderly males.
AB  - BACKGROUND: Loneliness and depression are very common in the aged population.
      Both have negative impacts on cognition in the elderly. The present study aimed
      to investigate the effect of loneliness and depression on total as well as
      specific cognitive domains in cognitively normal male subjects. MATERIAL/METHODS:
      A total of 189 cognitively normal male subjects were recruited and underwent
      Cognitive Abilities Screening Instrument (CASI) and Wechsler Digit Span Task
      tests. Depression was assessed by the Geriatric Depression Scale-Short Form (GDS
      SF) and loneliness by UCLA loneliness scales. Partial correlation test was used
      to explore the correlation between loneliness/depression and total as well as
      specific cognition function, with the controlled factors of age and education.
      RESULTS: Both depression and loneliness are negatively correlated with global
      cognitive function as evaluated with CASI (r=-0.227, p=0.002; r=-0.214, p=0.003,
      respectively). The domains of Attention, Orientation, Abstraction and judgment,
      and List-generating fluency of cognitive function were specifically associated
      with loneliness, and the domain of orientation was associated with depression
      after controlling the factors age and years of education. CONCLUSIONS: Our
      findings suggest that loneliness and depression may have negative impacts on
      global and specific domains of cognitive function in non-demented elderly males.
      Both loneliness and depression should be actively recognized earlier and
      appropriately treated because they are significant sources of cognitive
      impairment in the elderly.

PMID- 25575227
TI  - [Letter. Subsyndromal delirium].

PMID- 25575228
TI  - [News from the international literature].

PMID- 25575229
TI  - [Pitfalls of anesthesiologic management in operative or interventional securing
      of aneurysm].
AB  - Despite significant advances in operative, interventional and perioperative
      management aneurysmal subarachnoid hemorrhage is still associated with high rates
      of 30-day mortality in 35% and severe impairments in neurologic functional
      outcomes in up to 50% of the survivors. Apart from severity of initial brain
      injury prognosis depends on the extent of secondary brain injury triggered by re
      rupture, vasospasm, hydrocephalus and/ or further operative, interventional or
      intensive-care associated complications. Due to the complexity of disease the
      paper exclusively deals with pitfalls of anesthesiologic management in operative
      and non-operative aneurysm repair.

PMID- 25575230
TI  - [Case report - a dangerous intoxication after ingestion of alkyl nitrite
      ("poppers")].
AB  - This case report describes the inadvertent poisoning of a young man with
      "poppers" after having ingested an unknown amout of the drug. "Poppers" (alkyl
      nitrite) were made famous in the 1960s as a party drug, and during certain sexual
      practices, and are still in use today. The drug's inhalation leads to a short
      lived rush, vasodilation and relaxtion of smooth muscles. An accidental ingestion
      can lead to a significant build-up of methemoglobin with dire consequences. The
      therapy consists of the intravenous administration of methylene blue.

PMID- 25575231
TI  - [Mass casualty incidents - current concepts and developments].
AB  - Medical concepts and strategies are permanently changing. Due to the emergency
      response in a mass casualty incident everyone who is involved has to work
      together with different organisations and public authorities, which are not part
      of the regular emergency medical service. Within the last 25 years throughout the
      whole country of Germany the role of a "chief emergency physician" has been
      implemented and in preparation for the FIFA World Cup 2006 mobile treatment units
      were set up. In 2007, special units of the "Medical Task Force" - funded by the
      german state - were introduced and have been established by now. They will be a
      permanent part of regional plannings for mass casualty incidents. This article
      highlights current concepts and developments in different parts of Germany.

PMID- 25575232
TI  - [Diclofenac up2date - Part 2: The use in specific groups of patients].
AB  - The non-opioid analgesic diclofenac is used worldwide for musculoskeletal and
      perioperative pain therapy. Despite its frequent use and easy access as an "over
      the counter" drug, gastrointestinal, cardiovascular, and renal adverse drug
      effects have to be considered. Availability of diverse formulations (e.g.
      tablets, suppository, gel-formulations) with different indications, dosage
      recommendations and contraindications may easily lead to confusion, thus
      accounting for inadequate use on the one hand or withholding of an effective
      analgesic. This review may provide physicians in perioperative medicine,
      intensive care and pain therapy with important and suitable information about the
      pharmacology and appropriate use of this drug. 

PMID- 25575233
TI  - [Echocardiography - What you should know?].

PMID- 25575234
TI  - ["Introduction to transthoracic, transesophageal and real time 3Dimensional
      transesophageal echocardiography"].
AB  - Echocardiography allows assessment of cardiac anatomy and function. A tailored
      approach to echocardiographic assessment is essential in hemodynamic unstable
      patients. Standard views allow comprehensive examination and also reduce the
      chances to oversee unexpected findings. TTE should be first choice in emergency
      and intensive care medicine. TEE is standard of care in intraoperative setting. 3
      D echocardiography is valuable in specific situations. Written reporting of
      examination is mandatory.

PMID- 25575235
TI  - [Echocardiography - hemodynamically focused echocardiography].
AB  - Based on the previously published international evidence-based recommendations
      for focused cardiac ultrasound, aim of this paper is to provide a possible
      approach to the complementary application of TTE and TOE in hemodynamically
      unstable patients. Thereby the cardiac ultrasound examination is centered on the
      search of an answer or solution to a clinically relevant question or problem and
      does not replace an all-encompassing examination performed by cardiologists. 

PMID- 25575236
TI  - [Echocardiography for hemodynamic monitoring on ICU?].
AB  - A goal-directed hemodynamic therapy (GDT) using volume substitution and/or
      cardiovascular agents in order to increase stroke volume and consecutively tissue
      oxygenation has been shown to reduce perioperative complications. Previous
      hemodynamic monitoring devices mostly are only able to detect a restriction in
      several parameters of cardiovascular function not always diagnostically
      conclusive to their pathophysiological cause. However, this is mandatory for GDT.
      In this context, discontinuous transthoracic (TTE) and transesophageal (TEE)
      echocardiography is gaining clinical relevance. In addition, recently there
      exists the opportunity to perform a continuous hemodynamic focused
      transesophageal echocardiography ("hemodynamic TEE", hTEE) via a miniaturized
      monoplane probe. With its flexible probe tip the three most important two
      dimensional views of the heart can be obtained to differentiate between
      aforementioned pathophysiological causes of a low cardiac output syndrome. It is
      introduced orally in the patient's esophagus and can remain up to 72 hours in
      situ. First clinical reports/studies were able to demonstrate that a short
      intensive training programme for physicians unexperienced in echocardiography was
      sufficient to adequately initiate GDT. However, further studies have to prove the
      clinical feasibility and the positive effect on patient's outcome.

PMID- 25575237
TI  - [Nobel Prize for a " Egg of Columbus " ? Pioneers and priority challenges to the
      invention of the lumbar puncture and anesthesia].

PMID- 25575241
TI  - Targeted delivery of a sialic acid-blocking glycomimetic to cancer cells inhibits
      metastatic spread.
AB  - Sialic acid sugars are overexpressed by cancer cells and contribute to the
      metastatic cascade at multiple levels. Therapeutic interference of sialic acids,
      however, has been difficult to pursue because of the absence of dedicated tools.
      Here we show that a rationally designed sialic acid-blocking glycomimetic (P
      3F(ax)-Neu5Ac) successfully prevents cancer metastasis. Formulation of P-3F(ax)-
      Neu5Ac into poly(lactic-co-glycolic acid nanoparticles coated with antityrosinase
      related protein-1 antibodies allowed targeted delivery of P-3F(ax)--Neu5Ac into
      melanoma cells, slow release, and long-term sialic acid blockade. Most
      importantly, intravenous injections of melanoma-targeting P-3F(ax)--Neu5Ac
      nanoparticles prevented metastasis formation in a murine lung metastasis model.
      These findings stress the importance of sialoglycans in cancer metastasis and
      advocate that sialic acid blockade using rationally designed glycomimetics
      targeted to cancer cells can effectively prevent cancer metastases. This
      targeting strategy to interfere with sialic acid-dependent processes is broadly
      applicable not only for different types of cancer but also in infection and
      inflammation.

PMID- 25575242
TI  - CCR7-dependent trafficking of RORgamma+ ILCs creates a unique microenvironment
      within mucosal draining lymph nodes.
AB  - Presentation of peptide:MHCII by RORgamma-expressing group 3 innate lymphoid
      cells (ILC3s), which are enriched within gut tissue, is required for control of
      CD4 T-cell responses to commensal bacteria. It is not known whether ILC
      populations migrate from their mucosal and peripheral sites to local draining
      secondary lymphoid tissues. Here we demonstrate that ILC3s reside within the
      interfollicular areas of mucosal draining lymph nodes, forming a distinct
      microenvironment not observed in peripheral lymph nodes. By photoconverting
      intestinal cells in Kaede mice we reveal constitutive trafficking of ILCs from
      the intestine to the draining mesenteric lymph nodes, which specifically for the
      LTi-like ILC3s was CCR7-dependent. Thus, ILC populations traffic to draining
      lymph nodes using different mechanisms. 

PMID- 25575244
TI  - Ultrasound guidance versus anatomical landmarks for internal jugular vein
      catheterization.
AB  - BACKGROUND: Central venous catheters (CVCs) can help with diagnosis and treatment
      of the critically ill. The catheter may be placed in a large vein in the neck
      (internal jugular vein), upper chest (subclavian vein) or groin (femoral vein).
      Whilst this is beneficial overall, inserting the catheter risks arterial puncture
      and other complications and should be performed with as few attempts as possible.
      Traditionally, anatomical 'landmarks' on the body surface were used to find the
      correct place in which to insert catheters, but ultrasound imaging is now
      available. A Doppler mode is sometimes used to supplement plain 'two-dimensional'
      ultrasound. OBJECTIVES: The primary objective of this review was to evaluate the
      effectiveness and safety of two-dimensional (imaging ultrasound (US) or
      ultrasound Doppler (USD)) guided puncture techniques for insertion of central
      venous catheters via the internal jugular vein in adults and children. We
      assessed whether there was a difference in complication rates between traditional
      landmark-guided and any ultrasound-guided central vein puncture.Our secondary
      objectives were to assess whether the effect differs between US and USD; whether
      the effect differs between ultrasound used throughout the puncture ('direct') and
      ultrasound used only to identify and mark the vein before the start of the
      puncture procedure (indirect'); and whether the effect differs between different
      groups of patients or between different levels of experience among those
      inserting the catheters. SEARCH METHODS: We searched the Central Register of
      Controlled Trials (CENTRAL) (2013, Issue 1), MEDLINE (1966 to 15 January 2013),
      EMBASE (1966 to 15 January 2013), the Cumulative Index to Nursing and Allied
      Health Literature (CINAHL) (1982 to 15 January 2013 ), reference lists of
      articles, 'grey literature' and dissertations. An additional handsearch focused
      on intensive care and anaesthesia journals and abstracts and proceedings of
      scientific meetings. We attempted to identify unpublished or ongoing studies by
      contacting companies and experts in the field, and we searched trial registers.
      We reran the search in August 2014. We will deal with identified studies of
      interest when we update the review. SELECTION CRITERIA: We included randomized
      and quasi-randomized controlled trials comparing two-dimensional ultrasound or
      Doppler ultrasound with an anatomical 'landmark' technique during insertion of
      internal jugular venous catheters in both adults and children. DATA COLLECTION
      AND ANALYSIS: Three review authors independently extracted data on methodological
      quality, participants, interventions and outcomes of interest using a
      standardized form. A priori, we aimed to perform subgroup analyses, when
      possible, for adults and children, and for experienced operators and
      inexperienced operators. MAIN RESULTS: Of 735 identified citations, 35 studies
      enrolling 5108 participants fulfilled the inclusion criteria. The quality of
      evidence was very low for most of the outcomes and was moderate at best for four
      of the outcomes. Most trials had an unclear risk of bias across the six domains,
      and heterogeneity among the studies was significant.Use of two-dimensional
      ultrasound reduced the rate of total complications overall by 71% (14 trials,
      2406 participants, risk ratio (RR) 0.29, 95% confidence interval (CI) 0.17 to
      0.52; P value < 0.0001, I2 = 57%), and the number of participants with an
      inadvertent arterial puncture by 72% (22 trials, 4388 participants, RR 0.28, 95%
      CI 0.18 to 0.44; P value < 0.00001, I2 = 35%). Overall success rates were
      modestly increased in all groups combined at 12% (23 trials, 4340 participants,
      RR 1.12, 95% CI 1.08 to 1.17; P value < 0.00001, I2 = 85%), and similar benefit
      was noted across all subgroups. The number of attempts needed for successful
      cannulation was decreased overall (16 trials, 3302 participants, mean difference
      (MD) -1.19 attempts, 95% CI -1.45 to -0.92; P value < 0.00001, I2 = 96%) and in
      all subgroups. Use of two-dimensional ultrasound increased the chance of success
      at the first attempt by 57% (18 trials, 2681 participants, RR 1.57, 95% CI 1.36
      to 1.82; P value < 0.00001, I2 = 82%) and reduced the chance of haematoma
      formation (overall reduction 73%, 13 trials, 3233 participants, RR 0.27, 95% CI
      0.13 to 0.55; P value 0.0004, I2 = 54%). Use of two-dimensional ultrasound
      decreased the time to successful cannulation by 30.52 seconds (MD -30.52 seconds,
      95% CI -55.21 to -5.82; P value 0.02, I2 = 97%). Additional data are available to
      support use of ultrasound during, not simply before, line insertion.Use of
      Doppler ultrasound increased the chance of success at the first attempt by 58%
      (four trials, 199 participants, RR 1.58, 95% CI 1.02 to 2.43; P value 0.04, I2 =
      57%). No evidence showed a difference for the total numbers of perioperative and
      postoperative complications/adverse events (three trials, 93 participants, RR
      0.52, 95% CI 0.16 to 1.71; P value 0.28), the overall success rate (seven trials,
      289 participants, RR 1.09, 95% CI 0.95 to 1.25; P value 0.20), the total number
      of attempts until success (two trials, 69 participants, MD -0.63, 95% CI -1.92 to
      0.66; P value 0.34), the overall number of participants with an arterial puncture
      (six trials, 213 participants, RR 0.61, 95% CI 0.21 to 1.73; P value 0.35) and
      time to successful cannulation (five trials, 214 participants, each using a
      different definition for this outcome; MD 62.04 seconds, 95% CI -13.47 to 137.55;
      P value 0.11) when Doppler ultrasound was used. It was not possible to perform
      analyses for the other outcomes because they were reported in only one trial.
      AUTHORS' CONCLUSIONS: Based on available data, we conclude that two-dimensional
      ultrasound offers gains in safety and quality when compared with an anatomical
      landmark technique. Because of missing data, we did not compare effects with
      experienced versus inexperienced operators for all outcomes (arterial puncture,
      haematoma formation, other complications, success with attempt number one), and
      so the relative utility of ultrasound in these groups remains unclear and no data
      are available on use of this technique in patients at high risk of complications.
      The results for Doppler ultrasound techniques versus anatomical landmark
      techniques are also uncertain.

PMID- 25575243
TI  - Cell type-specific modifications of corticotropin-releasing factor (CRF) and its
      type 1 receptor (CRF1) on startle behavior and sensorimotor gating.
AB  - The corticotropin-releasing factor (CRF) family of peptides and receptors
      coordinates the mammalian endocrine, autonomic, and behavioral responses to
      stress. Excessive CRF production has been implicated in the etiology of stress
      sensitive psychiatric disorders such as posttraumatic stress disorder (PTSD),
      which is associated with alterations in startle plasticity. The CRF family of
      peptides and receptors mediate acute startle response changes during stress, and
      chronic CRF activation can induce startle abnormalities. To determine what neural
      circuits modulate startle in response to chronic CRF activation, transgenic mice
      overexpressing CRF throughout the central nervous system (CNS; CRF-COE(CNS)) or
      restricted to inhibitory GABAergic neurons (CRF-COE(GABA)) were compared across
      multiple domains of startle plasticity. CRF overexpression throughout the CNS
      increased startle magnitude and reduced ability to inhibit startle (decreased
      habituation and decreased prepulse inhibition (PPI)), similar to previous reports
      of exogenous effects of CRF. Conversely, CRF overexpression confined to
      inhibitory neurons decreased startle magnitude but had no effect on inhibitory
      measures. Acute CRF receptor 1 (CRF1) antagonist treatment attenuated only the
      effects on startle induced by CNS-specific CRF overexpression. Specific deletion
      of CRF1 receptors from forebrain principal neurons failed to alter the effects of
      exogenous CRF or stress on startle, suggesting that these CRF1 expressing neurons
      are not required for CRF-induced changes in startle behaviors. These data
      indicate that the effects of CRF activation on startle behavior utilize an
      extensive neural circuit that includes both forebrain and non-forebrain regions.
      Furthermore, these findings suggest that the neural source of increased CRF
      release determines the startle phenotype elicited. It is conceivable that this
      may explain why disorders characterized by increased CRF in cerebrospinal fluid
      (e.g. PTSD and major depressive disorder) have distinct symptom profiles in terms
      of startle reactivity. 

PMID- 25575245
TI  - Ultrasound guidance versus anatomical landmarks for subclavian or femoral vein
      catheterization.
AB  - BACKGROUND: Central venous catheters can help with diagnosis and treatment of the
      critically ill. The catheter may be placed in a large vein in the neck (internal
      jugular vein), upper chest (subclavian vein) or groin (femoral vein). Whilst this
      is beneficial overall, inserting the catheter risks arterial puncture and other
      complications and should be performed in as few attempts as possible.In the past,
      anatomical 'landmarks' on the body surface were used to find the correct place to
      insert these catheters, but ultrasound imaging is now available. A Doppler mode
      is sometimes used to supplement plain 'two-dimensional' ultrasound. OBJECTIVES:
      The primary objective of this review was to evaluate the effectiveness and safety
      of two-dimensional ultrasound (US)- or Doppler ultrasound (USD)-guided puncture
      techniques for subclavian vein, axillary vein and femoral vein puncture during
      central venous catheter insertion in adults and children. We assessed whether
      there was a difference in complication rates between traditional landmark-guided
      and any ultrasound-guided central vein puncture.When possible, we also assessed
      the following secondary objectives: whether a possible difference could be
      verified with use of the US technique versus the USD technique; whether there was
      a difference between using ultrasound throughout the puncture ('direct') and
      using it only to identify and mark the vein before starting the puncture
      procedure ('indirect'); and whether these possible differences might be evident
      in different groups of patients or with different levels of experience among
      those inserting the catheters. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (2013, Issue 1), MEDLINE (1966 to 15
      January 2013), EMBASE (1966 to 15 January 2013), the Cumulative Index to Nursing
      and Allied Health Literature (CINAHL) (1982 to 15 January 2013), reference lists
      of articles, 'grey literature' and dissertations. An additional handsearch
      focused on intensive care and anaesthesia journals and abstracts and proceedings
      of scientific meetings. We attempted to identify unpublished or ongoing studies
      by contacting companies and experts in the field, and we searched trial
      registers. We reran the search in August 2014. We will deal with any studies of
      interest when we update the review. SELECTION CRITERIA: Randomized and quasi
      randomized controlled trials comparing two-dimensional ultrasound or Doppler
      ultrasound versus an anatomical 'landmark' technique during insertion of
      subclavian or femoral venous catheters in both adults and children. DATA
      COLLECTION AND ANALYSIS: Three review authors independently extracted data on
      methodological quality, participants, interventions and outcomes of interest
      using a standardized form. We performed a priori subgroup analyses. MAIN RESULTS:
      Altogether 13 studies enrolling 2341 participants (and involving 2360 procedures)
      fulfilled the inclusion criteria. The quality of evidence was very low
      (subclavian vein N = 3) or low (subclavian vein N = 4, femoral vein N = 2) for
      most outcomes, moderate for one outcome (femoral vein) and high at best for two
      outcomes (subclavian vein N = 1, femoral vein N = 1). Most of the trials had
      unclear risk of bias across the six domains, and heterogeneity among the studies
      was significant.For the subclavian vein (nine studies, 2030 participants, 2049
      procedures), two-dimensional ultrasound reduced the risk of inadvertent arterial
      puncture (three trials, 498 participants, risk ratio (RR) 0.21, 95% confidence
      interval (CI) 0.06 to 0.82; P value 0.02, I2 = 0%) and haematoma formation (three
      trials, 498 participants, RR 0.26, 95% CI 0.09 to 0.76; P value 0.01, I2 = 0%).
      No evidence was found of a difference in total or other complications (together,
      US, USD), overall (together, US, USD), number of attempts until success (US) or
      first-time (US) success rates or time taken to insert the catheter (US).For the
      femoral vein, fewer data were available for analysis (four studies, 311
      participants, 311 procedures). No evidence was found of a difference in
      inadvertent arterial puncture or other complications. However, success on the
      first attempt was more likely with ultrasound (three trials, 224 participants, RR
      1.73, 95% CI 1.34 to 2.22; P value < 0.0001, I2 = 31%), and a small increase in
      the overall success rate was noted (RR 1.11, 95% CI 1.00 to 1.23; P value 0.06,
      I2 = 50%). No data on mortality or participant-reported outcomes were provided.
      AUTHORS' CONCLUSIONS: On the basis of available data, we conclude that two
      dimensional ultrasound offers small gains in safety and quality when compared
      with an anatomical landmark technique for subclavian (arterial puncture,
      haematoma formation) or femoral vein (success on the first attempt) cannulation
      for central vein catheterization. Data on insertion by inexperienced or
      experienced users, or on patients at high risk for complications, are lacking.
      The results for Doppler ultrasound techniques versus anatomical landmark
      techniques are uncertain.

PMID- 25575246
TI  - Provocative dose of methacholine causing a 20% drop in FEV1 should be used to
      interpret methacholine challenge tests with modern nebulizers.
AB  - RATIONALE: The American Thoracic Society guidelines (1999) for methacholine
      challenge tests (MCTs) using the 2-minute tidal breathing protocol were developed
      for the now-obsolete English-Wright (EW) nebulizer. In addition, the guideline
      recommendation to use the provocative concentration of methacholine causing a 20%
      drop in FEV1 (PC20) rather than the provocative dose of methacholine causing a
      20% drop in FEV1 (PD20) for determining the level of bronchial
      hyperresponsiveness has been challenged. OBJECTIVES: To determine if cumulative
      dose or concentration of methacholine delivered to the airways is the determinant
      for airway responsiveness and to validate use of the AeroEclipse* II BAN (Aero;
      Trudell Medical International, London, ON, Canada) nebulizer compared with use of
      the reference standard EW nebulizer. METHODS: Subjects with asthma (10-18 yr old)
      participated in randomized, controlled cross-over experiments comparing four MCT
      protocols using standard methacholine concentrations, but varying: (1)
      methacholine starting concentration (testing for cumulative effect); (2)
      nebulizer (EW versus Aero); and (3) inhalation time. PD20 was calculated using
      nebulizer output rate, inhalation time, and preceding doses delivered. ANOVA
      analyses were used to compare geometric means of PC20 and PD20 between protocols.
      RESULTS: A total of 32 subjects (17 male) participated. PC20 differed when
      starting concentration varied (0.46 vs. 0.80 mg/ml; P<0.0001), whereas PD20 did
      not (0.06 vs. 0.08 mg). PC20 differed with the EW versus the Aero nebulzer with
      30-second inhalation (1.19 vs. 0.43 mg/ml; P=0.0006) and the EW versus the Aero
      nebulizer with 20-second inhalation (1.91 vs. 0.89 mg/ml; P=0.0027), whereas PD20
      did not (0.07 vs. 0.06 mg and 0.11 vs. 0.09 mg, respectively). CONCLUSIONS: In
      MCTs, the cumulative dose (PD20), not the PC20, determines bronchial
      responsiveness. Modern nebulizers may be used for the test if clinical
      interpretation is based on PD20. Clinical trial registered with
      www.clinicaltrials.gov (NCT01288482).

PMID- 25575248
TI  - MRI-guided brain PET image filtering and partial volume correction.
AB  - Positron emission tomography (PET) image quantification is a challenging problem
      due to limited spatial resolution of acquired data and the resulting partial
      volume effects (PVE), which depend on the size of the structure studied in
      relation to the spatial resolution and which may lead to over or underestimation
      of the true tissue tracer concentration. In addition, it is usually necessary to
      perform image smoothing either during image reconstruction or afterwards to
      achieve a reasonable signal-to-noise ratio. Typically, an isotropic Gaussian
      filtering (GF) is used for this purpose. However, the noise suppression is at the
      cost of deteriorating spatial resolution. As hybrid imaging devices such as
      PET/MRI have become available, the complementary information derived from high
      definition morphologic images could be used to improve the quality of PET images.
      In this study, first of all, we propose an MRI-guided PET filtering method by
      adapting a recently proposed local linear model and then incorporate PVE into the
      model to get a new partial volume correction (PVC) method without parcellation of
      MRI. In addition, both the new filtering and PVC are voxel-wise non-iterative
      methods. The performance of the proposed methods were investigated with simulated
      dynamic FDG brain dataset and (18)F-FDG brain data of a cervical cancer patient
      acquired with a simultaneous hybrid PET/MR scanner. The initial simulation
      results demonstrated that MRI-guided PET image filtering can produce less noisy
      images than traditional GF and bias and coefficient of variation can be further
      reduced by MRI-guided PET PVC. Moreover, structures can be much better delineated
      in MRI-guided PET PVC for real brain data. 

PMID- 25575250
TI  - Sorption of grape proanthocyanidins and wine polyphenols by yeasts, inactivated
      yeasts, and yeast cell walls.
AB  - Inactivated yeast fractions (IYFs) can be used in enology to improve the
      stability and mouthfeel of red wines. However, information concerning the
      mechanisms involved and the impact of the IYF characteristics is scarce.
      Adsorption isotherms were used to investigate interactions between grape
      proanthocyanidin fractions (PAs) or wine polyphenols (WP) and a commercial yeast
      strain (Y), the inactivated yeast (IY), the yeast submitted to autolyzis and
      inactivation (A-IY), and the cell walls obtained by mechanical disruption (CW).
      High affinity isotherms and high adsorption capacities were observed for grape
      PAs and whole cells (Y, IY, and A-IY). Affinity and adsorbed amount were lower
      with wine PAs, due to chemical changes occurring during winemaking. By contrast
      to whole cells, grape PAs and WP adsorption on CW remained very low. This raises
      the issue of the part played by cell walls in the interactions between yeast and
      proanthocyanidins and suggests the passage of the latter through the wall pores
      and their interaction with the plasma membrane. 

PMID- 25575249
TI  - Functionalized cyclopentenes through a tandem NHC-catalyzed dynamic kinetic
      resolution and ambient temperature decarboxylation: mechanistic insight and
      synthetic application.
AB  - An unusual room temperature beta-lactone decarboxylation facilitated a five-step
      enantioselective formal synthesis of the cyclopentane core of an estrogen
      receptor beta-agonist. A computational study probed the underlying factors
      facilitating unprecedented, rapid decarboxylation. Aryl substitution promotes
      faster reaction in the retro-[2+2] as a result of conjugative stabilization with
      the forming olefin. Additionally, the configuration of the alpha-ester in these
      fused beta-lactones leads to differential decarboxylation rates. 

PMID- 25575251
TI  - Trainee Involvement in Surgery Is an Asset to the Surgical Team.

PMID- 25575252
TI  - Quality of conduct and reporting of meta-analyses of surgical interventions.
AB  - BACKGROUND: Meta-analyses are useful tools for summarizing surgical evidence as
      they aim to encompass multiple sources of information on a particular research
      question, but they may be prone to methodological and reporting biases. We
      evaluated the conduct and reporting of meta-analyses of surgical interventions.
      METHODS AND FINDINGS: We performed a systematic review of 150 meta-analyses of
      randomized trials of surgical interventions published between January 2010 and
      June 2011. A comprehensive search strategy was executed using MEDLINE, EMBASE,
      and the Cochrane Database of Systematic Reviews. Data were independently
      extracted by 2 authors using the PRISMA statement (preferred reporting items for
      systematic reviews and meta-analyses, a standardized quality of reporting
      guideline) and AMSTAR (a tool for methodological quality). Descriptive statistics
      were used for individual items, and as a measure of overall compliance, PRISMA
      and AMSTAR scores were calculated as the sum of adequately reported domains. A
      median of 8 trials (interquartile range = 8) was included in each meta-analysis.
      One third of all meta-analyses had an author with a background in epidemiology
      and/or statistics. Forty-four percent were published in PRISMA-endorsing journals
      with a median impact factor of 3.5. There was moderate compliance with PRISMA,
      with an average of 71% of items reported, but poorer compliance with AMSTAR, with
      48% of items adequately described, on average. CONCLUSIONS: Substantial gaps in
      the conduct and reporting of meta-analyses within the surgical literature exist,
      mainly in the specification of aims and/or objectives, the use of preplanned
      protocols, and the evaluation of potential bias at the review (rather than trial)
      level. Editorial insistence on using reporting guidelines would improve this
      situation.

PMID- 25575254
TI  - Randomized controlled trial of the use of a large-pore polypropylene mesh to
      prevent incisional hernia in colorectal surgery.
AB  - OBJECTIVE: To reduce the incidence of incisional hernia (IH) in colorectal
      surgery by implanting a mesh on the overlay position. BACKGROUND: The incidence
      of IH in colorectal surgery may be as high as 40%. IH causes severe health and
      cosmetic problems, and its repair increases health care costs. MATERIAL AND
      METHODS: Randomized, controlled, prospective trial. Patients undergoing any
      colorectal procedure (both elective and emergency) through a midline laparotomy
      were divided into 2 groups. The abdomen was closed with an identical technique in
      both groups, except for the implantation of an overlay large-pore polypropylene
      mesh in the study group. Patients were followed up clinically and radiologically
      for 24 months. RESULTS: A total of 107 patients were included: 53 in the study
      group and 54 in the control group. Both groups were homogeneous, except for a
      higher incidence of diabetes in the mesh group. There were 20 emergency
      procedures in the study group and 17 in the control group. There were no
      statistical differences in surgical site infections, seromas, or mortality
      between the groups (33.3%, 13.8%, and 3.7% in the control group and 18.9%, 13.2%,
      and 3.8% in the study group). No mesh rejection was reported. The incidence of IH
      was 17 of 54 (31.5%) in the control group and 6 of 53 (11.3%) in the study group
      (P = 0.011). CONCLUSIONS: The incidence of IH is high in patients undergoing
      elective or emergency surgery for colorectal diseases. The addition of a
      prophylactic large-pore polypropylene mesh on the overlay position decreases the
      incidence of IH without adding morbidity.

PMID- 25575253
TI  - Minimally invasive esophagectomy: results of a prospective phase II multicenter
      trial-the eastern cooperative oncology group (E2202) study.
AB  - OBJECTIVE: The primary aim of this trial was to assess the feasibility of
      minimally invasive esophagectomy (MIE) in a multi-institutional setting.
      BACKGROUND: Esophagectomy is an important, potentially curative treatment for
      localized esophageal cancer, but is a complex operation. MIE may decrease the
      morbidity and mortality of resection, and single-institution studies have
      demonstrated successful outcomes with MIE. METHODS: We conducted a multicenter,
      phase II, prospective, cooperative group study (coordinated by the Eastern
      Cooperative Oncology Group) to evaluate the feasibility of MIE. Patients with
      biopsy-proven high-grade dysplasia or esophageal cancer were enrolled at 17
      credentialed sites. Protocol surgery consisted of either 3-stage MIE or Ivor
      Lewis MIE. The primary end point was 30-day mortality. Secondary end points
      included adverse events, duration of hospital-stay, and 3-year outcomes. RESULTS:
      Protocol surgery was completed in 95 of the 104 patients eligible for the primary
      analysis (91.3%). The 30-day mortality in eligible patients who underwent MIE was
      2.1%; perioperative mortality in all registered patients eligible for primary
      analysis was 2.9%. Median intensive care unit and hospital stay were 2 and 9
      days, respectively. Grade 3 or higher adverse events included anastomotic leak
      (8.6%), acute respiratory distress syndrome (5.7%), pneumonitis (3.8%), and
      atrial fibrillation (2.9%). At a median follow-up of 35.8 months, the estimated 3
      year overall survival was 58.4% (95% confidence interval: 47.7%-67.6%).
      Locoregional recurrence occurred in only 7 patients (6.7%). CONCLUSIONS: This
      prospective multicenter study demonstrated that MIE is feasible and safe with low
      perioperative morbidity and mortality and good oncological results. This approach
      can be adopted by other centers with appropriate expertise in open esophagectomy
      and minimally invasive surgery.

PMID- 25575255
TI  - Mass Spectrometric Analysis of Exhaled Breath for the Identification of Volatile
      Organic Compound Biomarkers in Esophageal and Gastric Adenocarcinoma.
AB  - OBJECTIVE: The present study assessed whether exhaled breath analysis using
      Selected Ion Flow Tube Mass Spectrometry could distinguish esophageal and gastric
      adenocarcinoma from noncancer controls. BACKGROUND: The majority of patients with
      upper gastrointestinal cancer present with advanced disease, resulting in poor
      long-term survival rates. Novel methods are needed to diagnose potentially
      curable upper gastrointestinal malignancies. METHODS: A Profile-3 Selected Ion
      Flow Tube Mass Spectrometry instrument was used for analysis of volatile organic
      compounds (VOCs) within exhaled breath samples. All study participants had
      undergone upper gastrointestinal endoscopy on the day of breath sampling.
      Receiver operating characteristic analysis and a diagnostic risk prediction model
      were used to assess the discriminatory accuracy of the identified VOCs. RESULTS:
      Exhaled breath samples were analyzed from 81 patients with esophageal (N = 48) or
      gastric adenocarcinoma (N = 33) and 129 controls including Barrett's metaplasia
      (N = 16), benign upper gastrointestinal diseases (N = 62), or a normal upper
      gastrointestinal tract (N = 51). Twelve VOCs-pentanoic acid, hexanoic acid,
      phenol, methyl phenol, ethyl phenol, butanal, pentanal, hexanal, heptanal,
      octanal, nonanal, and decanal-were present at significantly higher concentrations
      (P < 0.05) in the cancer groups than in the noncancer controls. The area under
      the ROC curve using these significant VOCs to discriminate esophageal and gastric
      adenocarcinoma from those with normal upper gastrointestinal tracts was 0.97 and
      0.98, respectively. The area under the ROC curve for the model and validation
      subsets of the diagnostic prediction model was 0.92 +/- 0.01 and 0.87 +/- 0.03,
      respectively. CONCLUSIONS: Distinct exhaled breath VOC profiles can distinguish
      patients with esophageal and gastric adenocarcinoma from noncancer controls.

PMID- 25575256
TI  - The Response to Burn Injury in Mice With Human Hematolymphoid Systems.
AB  - OBJECTIVE: To develop an animal model of injury that more closely represents the
      human inflammatory cell response to injury. BACKGROUND: Because the mouse
      inflammatory response to burn injury cannot account for the contribution of human
      specific genes, animal models are needed to more closely recapitulate the human
      inflammatory response and improve the translational impact of injury research. To
      this end, we hypothesized that the human inflammatory cell response to injury
      could be selectively assessed after severe burn injury using humanized mice.
      METHODS: NOD-Scid-IL2Rgamma null mice were transplanted with human hematopoietic
      CD34+ progenitor cells; their engraftment confirmed and then subjected to 30%
      total body surface area steam burn injury. Blood, bone marrow, and lung tissue
      were collected 4 hours after injury and human inflammatory cell mobilization
      analyzed using flow cytometry and immunohistochemistry. RESULTS: Burn injury
      caused mobilization of human inflammatory cells into the systemic circulation.
      Next, burn injury was accompanied by evidence of histologic lung injury and
      concomitant mobilization of human CD45+ immune cells into the lung that were
      associated with increased trafficking of human CD11b+ myeloid cells. CONCLUSIONS:
      These experiments are the first to demonstrate the suitability of humanized mice
      for injury research. They offer the possibility to address very specific research
      questions that are not amenable to traditional mouse models of injury, for
      example, the emerging role of certain human-specific genes that are either
      unrepresented or totally absent, from the mouse genome.

PMID- 25575257
TI  - Training autonomous surgeons: more time or faculty development?

PMID- 25575258
TI  - Gastrografin in Prolonged Postoperative Ileus: A Double-blinded Randomized
      Controlled Trial.
AB  - OBJECTIVE: To investigate the therapeutic value of Gastrografin in shortening
      duration of prolonged postoperative ileus (PPOI) after elective colorectal
      surgery. BACKGROUND: Gut wall edema is central to the pathogenesis of PPOI.
      Hyperosmotic, orally administered, water-soluble contrast media such as
      Gastrografin are theoretically capable of mitigating this edema. METHODS: A
      double-blinded, placebo-controlled, randomized trial was conducted. Participants
      were allocated to receive 100 mL of Gastrografin (Exposure Group) or flavored
      distilled water (Control Group) administered enterally. Other aspects of
      management were standardized. Resolution of PPOI was assessed 12-hourly. RESULTS:
      Eighty patients were randomized equally, with 5 in the Exposure Group and 4 in
      the Control Group excluded from analysis. Participants were evenly matched at
      baseline. Mean duration of PPOI did not differ between Exposure and Control
      Groups (83.7 vs 101.3 hours; P = 0.191). When considering individual markers of
      PPOI resolution, Gastrografin did not affect time to resolution of nausea and
      vomiting (64.5 vs 74.3 hours; P = 0.404) or consumption of oral diet (75.8 vs
      90.0 hours; P = 0.297). However, it accelerated time to flatus or stool (18.9 vs
      32.7 hours; P = 0.047) and time to resolution of abdominal distension (52.8 vs
      77.7 hours; P = 0.013). There were no significant differences between groups in
      nasogastric output; analgesia, antiemetic, or fluid requirement; complications;
      or length of stay. CONCLUSIONS: Gastrografin is not clinically useful in
      shortening an episode of PPOI characterized by upper and lower gastrointestinal
      symptoms. It may however be of therapeutic benefit in the subset of PPOI patients
      who display lower gastrointestinal symptoms exclusively after surgery.

PMID- 25575259
TI  - Does Preoperative Neutrophil to Lymphocyte Ratio Predict Disease-Free Survival
      Rate in Colorectal Cancer Patients Undergoing Curative Surgery?

PMID- 25575260
TI  - Cumulative Metformin Use and Its Impact on Survival in Gastric Cancer Patients
      After Gastrectomy.
AB  - OBJECTIVE: The aim of this study was to evaluate the association between
      metformin and survival of gastric cancer (GC) patients. BACKGROUND: Metformin has
      recently received attention as a potential anticancer treatment. However, no
      study has shown the survival benefit of metformin for GC patients. METHODS: A
      total of 1974 GC patients who underwent curative gastrectomy were compared for
      survival according to groups; 132 diabetic patients treated with metformin, 194
      diabetic patients without metformin, and 1648 non-diabetic patients. RESULTS:
      During the median follow-up period of 6.2 years (interquartile range, 4.7-7.8
      years), 381 patients (19.3%) died, including 302 (15.3%) who died from GC. The
      non-diabetic patients had significantly better recurrence-free survival (RFS; P <
      0.0001), cancer-specific survival (CSS; P = 0.006), and overall survival (OS; P <
      0.0001). However, the diabetic patients treated with metformin had a
      significantly better prognosis than those who were not (OS: hazard ratio [HR] =
      0.584, 95% confidence interval [CI], 0.369-0.926; CSS: HR = 0.57, 95% CI, 0.334
      0.975; RFS: HR = 0.633, 95% CI, 0.410-0.977), and metformin treatment prolonged
      survival in diabetic patients to a rate comparable to that in non-diabetic
      patients. In multivariable analysis using the Cox proportional hazard model with
      time-dependent covariates, each cumulative 6 months of metformin use was
      significantly associated with a decreased risk of recurrence, cancer-specific
      mortality, and all-cause mortality (RFS: HR = 0.864, 95% CI, 0.797-0.937; CSS: HR
      = 0.865, 95% CI, 0.782-0.958; OS: HR 0.870, 95% CI, 0.801-0.945). CONCLUSIONS:
      The increased cumulative duration of metformin use decreased the recurrence, all
      cause mortality, and cancer-specific mortality rates among GC patients with
      diabetes who underwent gastrectomy.

PMID- 25575261
TI  - Could Type and Size of Gallstones Influence Gallbladder Carcinogenesis?

PMID- 25575262
TI  - Synbiotics in Surgery for Chronic Pancreatitis: Are They Truly Effective? A
      Single-blind Prospective Randomized Control Trial.
AB  - BACKGROUND: Postoperative infectious complications in patients undergoing
      pancreatic surgery are a significant cause for morbidity and mortality. Although
      synbiotics have beneficial effects on human health, their clinical value in
      surgical patients remains unclear given a paucity of applicable clinical studies.
      AIM: To determine the impact of perioperative synbiotic therapy on postoperative
      infectious complications, morbidity and mortality in patients undergoing
      pancreatic surgery for chronic pancreatitis. METHODS: A trial was conducted in
      patients with chronic calcific pancreatitis undergoing Frey's procedure. Group A
      received a specific synbiotic composition, 5 days prior and 10 days after the
      surgery. Group B received a placebo. Primary study endpoint was the occurrence of
      postoperative infection during the first 30 days. Secondary outcome measures were
      mortality, length of hospital stay, days in intensive care unit, and duration of
      antibiotic therapy. Using previously accrued data, with alpha of 0.05 and power
      80%, the sample size was calculated as 35 patients for each group with a dropout
      rate of 10%. RESULTS: Of the 79 patients enrolled, 75 completed the trial [group
      A (n = 39) and group B (n = 36)]. The incidence of postoperative infectious
      complications (12.8% vs 39%; P < 0.05), duration of antibiotics therapy (P <
      0.05), and length of hospital stay (P < 0.05) were significantly lower in the
      synbiotic group. CONCLUSIONS: Synbiotics significantly reduce septic
      complications, hospital stay, and antibiotic requirement in patients undergoing
      pancreatic surgery for chronic pancreatitis. Furthermore, basic and clinical
      research would clarify the underlying mechanisms of their therapeutic effect and
      define the appropriate conditions for use.

PMID- 25575263
TI  - Should a Scheduled Colorectal Operation Have a Mechanical Bowel Prep,
      Preoperative Oral Antibiotics, Both, or Neither?

PMID- 25575264
TI  - Colorectal Cancer, Systemic Inflammation, and Outcome: Staging the Tumor and
      Staging the Host.
AB  - OBJECTIVE: This study aims to examine the clinical utility of the combination of
      TNM stage and modified Glasgow Prognostic Score (mGPS) in patients undergoing
      potentially curative resection of colorectal cancer (CRC). BACKGROUND: Of
      measures of the systemic inflammatory response, the mGPS has been most
      extensively validated in patients with cancer. METHODS: Data from 1000
      consecutive patients undergoing potentially curative CRC resection from a single
      institution (January 1997-May 2013) were included. The relationship between mGPS
      [0-C-reactive protein (CRP) <= 10 mg/L, 1-CRP > 10 mg/L and albumin >=35 g/L, 2
      CRP > 10 mg/L and albumin < 35 g/L], TNM stage, and cancer-specific survival
      (CSS) and overall survival (OS) was examined using Kaplan-Meier log-rank survival
      analysis and multivariate Cox regression analysis. RESULTS: An mGPS of 0, 1, and
      2 was observed in 63%, 21%, and 16% of patients, respectively. Median follow-up
      was 56 months (interquartile range: 28-107 months). TNM and mGPS were
      independently associated with CSS and OS (all P < 0.001). In all patients, TNM
      and mGPS stratified 5-year CSS and OS from 97% and 87% (stage I, mGPS = 0) to 32%
      and 26% (stage III, mGPS = 2), respectively. In patients undergoing elective
      resection of colon cancer (n = 575), 5-year CSS and OS ranged from 100% and 87%
      (stage I, mGPS = 0) to 37% and 30% (stage III, mGPS = 2), respectively.
      CONCLUSIONS: This study shows how the combination of TNM and mGPS effectively
      stratifies outcome in patients undergoing potentially curative resection of CRC.
      These data support routine staging of both the tumor and the host in patients
      with CRC.

PMID- 25575266
TI  - Proton-Coupled Electron Transfer During the S-State Transitions of the Oxygen
      Evolving Complex of Photosystem II.
AB  - The oxygen-evolving complex (OEC) of photosystem II (PSII) is a unique Mn4O5Ca
      cluster that catalyzes water oxidation via four photoactivated electron transfer
      steps. As the protein influence on the redox and protonation chemistry of the OEC
      remains an open question, we present a classical valence model of the OEC that
      allows the redox state of each Mn and the protonation state of bridging MU-oxos
      and terminal waters to remain in equilibrium with the PSII protein throughout the
      redox cycle. We find that the last bridging oxygen loses its proton during the
      transition from S0 to S1. Two possible S2 states are found depending on the OEC
      geometry: S2 has Mn4(IV) with a proton lost from a terminal water (W1) trapped by
      the nearby D1-D61 if O5 is closer to Mn4, or Mn1(IV), with partial deprotonation
      of D1-H337 and D1-E329 if O5 is closer to Mn1. In S3, the OEC is Mn4(IV) with W2
      deprotonated. The estimated OEC Em's range from +0.7 to +1.3 V, enabling
      oxidation by P680(+), the primary electron donor in PSII. In chloride-depleted
      PSII, the proton release increases during the S1 to S2 transition, leaving the
      OEC unable to properly advance through the water-splitting cycle. 

PMID- 25575265
TI  - Bile Routing Modification Reproduces Key Features of Gastric Bypass in Rat.
AB  - OBJECTIVE: To evaluate the role of bile routing modification on the beneficial
      effects of gastric bypass surgery on glucose and energy metabolism. BACKGROUND:
      Gastric bypass surgery (GBP) promotes early improvements in glucose and energy
      homeostasis in obese diabetic patients. A suggested mechanism associates a
      decrease in hepatic glucose production to an enhanced intestinal gluconeogenesis.
      Moreover, plasma bile acids are elevated after GBP and bile acids are inhibitors
      of gluconeogenesis. METHODS: In male Sprague-Dawley rats, we performed bile
      diversions from the bile duct to the midjejunum or the mid-ileum to match the
      modified bile delivery in the gut occurring in GBP. Body weight, food intake,
      glucose tolerance, insulin sensitivity, and food preference were analyzed. The
      expression of gluconeogenesis genes was evaluated in both the liver and the
      intestine. RESULTS: Bile diversions mimicking GBP promote an increase in plasma
      bile acids and a marked improvement in glucose control. Bile bioavailability
      modification is causal because a bile acid sequestrant suppresses the beneficial
      effects of bile diversions on glucose control. In agreement with the inhibitory
      role of bile acids on gluconeogenesis, bile diversions promote a blunting in
      hepatic glucose production, whereas intestinal gluconeogenesis is increased in
      the gut segments devoid of bile. In rats fed a high-fat-high-sucrose diet, bile
      diversions improve glucose control and dramatically decrease food intake because
      of an acquired disinterest in fatty food. CONCLUSIONS: This study shows that bile
      routing modification is a key mechanistic feature in the beneficial outcomes of
      GBP.

PMID- 25575268
TI  - International note: association between perceived resilience and health risk
      behaviours in homeless youth.
AB  - Homeless youth are regarded as an extremely high risk group, susceptible to
      suicidal ideation substance abuse, and high rates of mental illness. While there
      exists a substantial body of knowledge regarding resilience of homeless youth,
      few studies has examined the relationship between perceived resilience and health
      risk behaviours. The present study describes the findings from a quantitative
      examination of street-related demographics, resilience, suicidal ideation,
      substance abuse, sexual risk behaviours and violent related behaviours among 227
      homeless youth. The findings revealed that perceived resilience was negatively
      related to suicidal ideation, substance abuse and violence. Suicidal ideation was
      positively related to both substance abuse and violence, whilst violence and
      substance abuse were positively correlated. Multiple regressions showed that
      perceived resilience served as a protective factor for suicidal ideation and
      having multiple sexual lifetime partners, suggesting that youth with lower level
      of perceived resilience were more likely to engage in various health risks
      behaviours. 

PMID- 25575267
TI  - Development of phenotypic and transcriptional biomarkers to evaluate relative
      activity of potentially estrogenic chemicals in ovariectomized mice.
AB  - BACKGROUND: Concerns regarding potential endocrine-disrupting chemicals (EDCs)
      have led to a need for methods to evaluate candidate estrogenic chemicals. Our
      previous evaluations of two such EDCs revealed a response similar to that of
      estradiol (E2) at 2 hr, but a less robust response at 24 hr, similar to the short
      acting estrogen estriol (E3). OBJECTIVES: Microarray analysis using tools to
      recognize patterns of response have been utilized in the cancer field to develop
      biomarker panels of transcripts for diagnosis and selection of treatments most
      likely to be effective. Biological effects elicited by long- versus short-acting
      estrogens greatly affect the risks associated with exposures; therefore, we
      sought to develop tools to predict the ability of chemicals to maintain
      estrogenic responses. METHODS: We used biological end points in uterine tissue
      and a signature pattern-recognizing tool that identified coexpressed transcripts
      to develop and test a panel of transcripts in order to classify potentially
      estrogenic compounds using an in vivo system. The end points used are relevant to
      uterine tissue, but the resulting classification of the compounds is important
      for other sensitive tissues and species. RESULTS: We evaluated biological and
      transcriptional end points with proven short- and long-acting estrogens and
      verified the use of our approach using a phytoestrogen. With our model, we were
      able to classify the diarylheptanoid D3 as a short-acting estrogen. CONCLUSIONS:
      We have developed a panel of transcripts as biomarkers which, together with
      biological end points, might be used to screen and evaluate potentially
      estrogenic chemicals and infer mode of activity.

PMID- 25575269
TI  - The Post-Levator Aponeurosis Fat Pad.
AB  - PURPOSE: To examine the post-aponeurotic space and to confirm and define the
      presence of a post-aponeurosis fat-pad. METHODS: Experimental anatomic study.
      Nineteen-orbits from 10 freeze-preserved, unembalmed cadavers of caucasian
      subjects. In 12 orbits of 7 cadavers, a transconjunctival dissection of the
      everted upper eyelid was undertaken. Muller's muscle (MM) and conjunctiva were
      dissected as a composite flap exposing the posterior surface of the aponeurosis
      (LA) and the commencement of the levator palpebrae superioris (LPS) muscle.
      Anatomical localisation was agreed by 2 senior surgeons and an anatomist (VM). In
      the remaining 7 orbits a 1cm central upper eyelid wedge-excision was paraffin
      embedded and studied histologically. RESULTS: Nineteen upper-eyelids from 10
      freeze-preserved, unembalmed caucasian cadavers (5-male, 5-female, mean age 80.9;
      range 67-91 years) were studied. Of 12 eyelids of 7 cadavers, dissected and
      macroscopically evaluated, a fat-pad was identified in the post-aponeurotic space
      of all eyelids. Of these, 8 (66%) were predominantly diffuse. The remainder,
      mixed diffuse-discrete. All 4 of the latter category appeared multi-lobular. The
      fat-pad was seen to lie predominantly centro-medially, overlying MM, extending
      superiorly beyond the LA to lie posterior to LPS. Of the 7 upper eyelid wedge
      excisions examined microscopically, a fat-pad was identified in all post
      aponeurotic spaces, lying between 2 distinct tracts of smooth muscle. The
      anterior smooth muscle tract was intimately related to the posterior aspect of
      the LA, in keeping with the posterior smooth muscle layer of the aponeurosis. The
      posterior smooth muscle tract was in keeping with MM, thicker than the anterior
      layer, multi-layered and in 6 of 7 eyelids, interspersed with fat. CONCLUSIONS:
      We confirm and describe a distinct layer of fat in the post-aponeurotic space,
      consistently found between MM and the posterior smooth muscle layer of the
      aponeurosis. We refer to this as the post-aponeurosis fat-pad. These findings
      provide further anatomical detail for the surgeon undertaking blepharoptosis
      surgery, who may, in some cases, mistake the presence of fat in this space either
      for the pre-aponeurotic fat-pad, or for degenerative changes within MM that lies
      deep to it.

PMID- 25575270
TI  - Partial Molecular Characterization of Arctium minus Aspartylendopeptidase and
      Preparation of Bioactive Peptides by Whey Protein Hydrolysis.
AB  - In this article, we report the cloning of an aspartic protease (AP) from flowers
      of Arctium minus (Hill) Bernh. (Asteraceae) along with the use of depigmented
      aqueous flower extracts, as a source of APs, for the hydrolysis of whey proteins.
      The isolated cDNA encoded a protein product with 509 amino acids called
      arctiumisin, with the characteristic primary structure organization of typical
      plant APs. Bovine whey protein hydrolysates, obtained employing the enzyme
      extracts of A. minus flowers, displayed inhibitory angiotensin-converting enzyme
      (ACE) and antioxidant activities. Hydrolysates after 3 and 5 h of reaction
      (degree of hydrolysis 2.4 and 5.6, respectively) and the associated peptide
      fraction with molecular weight below 3 kDa were analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption
      ionization/time of flight mass spectrometry, and reverse phase-high-performance
      liquid chromatography. The results obtained in this study demonstrate the
      viability of using proteases from A. minus to increase the antioxidant and
      inhibitory ACE capacity of whey proteins. 

PMID- 25575271
TI  - An update on hypertensive emergencies and urgencies.
AB  - Severe acute arterial hypertension is usually defined as 'hypertensive crisis',
      although 'hypertensive emergencies' or 'hypertensive urgencies', as suggested by
      the Joint National Committee and the European Society of Hypertension, have
      completely different diagnostic and therapeutic approaches.The prevalence and
      demographics of hypertensive emergencies and urgencies have changed over the last
      four decades, but hypertensive emergencies and urgencies are still associated
      with significant morbidity and mortality.Different scientific societies have
      repeatedly produced up-to-date guidelines; however, the treatment of hypertensive
      emergencies and urgencies is still inappropriate, with potential clinical
      implications.This review focuses on hypertensive emergencies and urgencies
      management and treatment, as suggested by recent data. 

PMID- 25575272
TI  - An autopsy study of sudden cardiac death in persons aged 1-40 years in Brescia
      (Italy).
AB  - INTRODUCTION: Sudden cardiac death (SCD), above all when occurring in young
      people, remains a major clinical problem. We have analysed the clinical and post
      mortem findings of patients who were evaluated for SCD. METHODS AND RESULTS: We
      have analysed 54 cases of SCD which occurred in patients aged below 40 years
      during the period 1993-2012 and were studied at the Institute of Forensic
      Medicine of Brescia. The following variables were considered: sex, age, medical
      history, autopsy findings with special reference to macroscopic and histological
      evaluation of the heart and toxicological investigation. In all cases, we also
      performed the dissection of the cardiac conduction tissue with subsequent serial
      sampling and careful microscopic evaluation.Most SCD patients were men (76%),
      with a mean age of 27 years. The results of post mortem investigations have
      identified the following abnormalities: coronary artery disease (18.5%),
      arrhythmogenic right ventricular dysplasia (11.1%), hypertrophic obstructive
      cardiomyopathy (9.2%), severe valvular heart disease (7.4%) and myocarditis
      (7.4%). A case of persistence of the inter-atrial communication with cardiomegaly
      and right and left ventricular hypertrophy was also reported. Examination of the
      cardiac conduction tissue showed abnormalities in 12 cases (22.2%), in whom the
      heart was structurally normal at macroscopic examination. Despite all the
      investigations carried out, any pathogenic substrate that could have justified
      death was not found in 12 cases (22.2%). CONCLUSION: Our study underlines the
      value of an accurate routine post mortem investigation that may show an otherwise
      unsuspected structural heart disease. The serial study of the conduction tissue
      may provide pathologic substrates that may be responsible for the arrhythmic
      cause of death. A meaningful percentage of cases (22%) had no evidence of any
      abnormality. Genetic testing can be indicated in these cases.

PMID- 25575273
TI  - Enhanced platelet activity in atrial septal defect.
AB  - AIMS: Enhanced platelet activity assessed by mean platelet volume (MPV) was
      observed in pulmonary arterial hypertension. This study examined the presence of
      platelet activation in adults with atrial septal defect (ASD), its relationship
      with pulmonary vascular disease and its changes following device closure of the
      defects. METHODS: A total of 76 consecutive patients received transcatheter ASD
      closure and 40 matched healthy volunteers were prospectively enrolled for blood
      tests and transthoracic echocardiography (patients: aged 36 +/- 13, 37% men;
      controls: aged 36 +/- 8, 38% men). MPV, systolic pulmonary arterial pressures
      (PAP), and right ventricular end-diastolic diameters were collected before and
      after ASD closure in patients. RESULTS: The mean MPV levels were significantly
      higher in patients than in controls (10.1 +/- 1.3 to 8.6 +/- 0.9 fl; P < 0.001)
      at baseline. A moderate, positive correlation was also observed between baseline
      MPV levels and systolic PAP (r = 0.542, P < 0.001) in patients. Both MPV levels,
      systolic PAP and right ventricular end-diastolic diameters reduced significantly
      6 months following ASD closure. The 6-month MPV and systolic PAP values were
      comparable to those of the normals. CONCLUSION: Enhanced platelet activity was
      present in ASD and associated with the presence of pulmonary vascular disease.
      This phenomenon was largely reversible following device closure of the defects.

PMID- 25575274
TI  - Localizing factors in atherosclerosis.
AB  - Atherosclerotic vascular disease is the leading cause of death worldwide.
      Although the entire vascular bed is constantly exposed to the same risk factors,
      atheromatous lesions present a distinct intra-individual pattern of localization
      and progression, being consistently more frequent in specific segments of the
      arterial vascular bed. This peculiar distribution may be related to selective
      sensitivity of such locations to the influence of risk factors or to
      histopathological and flow differences, and has relevant clinical implications,
      as the prognosis of the disease varies according to localization. We here review
      the theories that have been formulated to explain such preferential locations, as
      its understanding can be useful to pursue diagnostic screening strategies and
      focused preventive measures. 

PMID- 25575275
TI  - Lung ultrasound and transthoracic impedance for noninvasive evaluation of
      pulmonary congestion in heart failure.
AB  - BACKGROUND: In patients with heart failure, many indexes are available for
      noninvasive identification of pulmonary congestion: E/E' at echocardiography;
      plasma levels of brain natriuretic peptide (BNP) (pg/ml); number of B-lines at
      lung ultrasound; and transthoracic conductance [thoracic fluid content (TFC)TT =
      1/Omega] at impedance cardiography (ICG). METHODS: We obtained 75 measures from
      50 patients (72 +/- 10 years, NYHA 2.4 +/- 0.7, ejection fraction 31 +/- 7%), 25
      of them studied before and after intravenous diuretics, in whom we assessed the
      following: E/e' from Doppler echocardiogram; BNP plasma levels; presence and
      number of B-lines at lung ultrasound; and TFCTT from ICG. We determined the
      relationship among these indexes and their change with treatment, and compared B
      lines and TFC for the diagnosis of pulmonary congestion. Finally, we considered
      the timing and the personnel required for performing and interpreting each test.
      RESULTS: A mutual relationship was observed between all the variables. After
      clinical improvement, changes in each variable were of similar direction and
      magnitude. Congestion (estimated by chest radiograph) was present in 59% of the
      patients: TFC value and B-line number had the best sensitivity and specificity
      for its detection. BNP determination and ICG assessment were performed by a nurse
      (15 min), and echocardiography and lung ultrasound were performed by a
      cardiologist (15 min). CONCLUSION: The correlation between all indexes and their
      consensual change after improvement of the clinical status suggests that they all
      detect pulmonary congestion, and that using at least two indexes improves
      sensitivity and specificity. The choice among the methods may be determined by
      the patient characteristics or by the clinical setting.

PMID- 25575276
TI  - Drug-eluting stent use after coronary atherectomy: results from a multicentre
      experience - The ROTALINK I study.
AB  - AIMS: Until now, there is no medium- to long-term clinical evidence of the best
      treatment after rotational atherectomy. METHODS: From the databases of seven high
      volume centres, years 2005-2010, we retrospectively analysed the long-term
      outcome of patients who had undergone rotational atherectomy followed by plain
      balloon angioplasty or implantation of drug-eluting stent (DES) or bare metal
      stent (BMS). Primary endpoint was the incidence of major adverse cardiovascular
      events (MACE: death, myocardial infarction, target-lesion-revascularization) at
      longest available follow-up. RESULTS: In this registry, we enrolled 1397 patients
      with 1605 lesions, followed for 28.4 +/- 21 months. DES-treated patients were
      more frequently diabetic, had more lesions treated and received a higher number
      of stents. In-hospital MACEs were significantly higher in DES patients (7.6 vs.
      2.6 vs. 2.9%, respectively, P = 0.0001 for both), mainly due to a higher
      incidence of myocardial infarction (6.4 vs. 1.2 vs. 2.1%, P = 0.0001). The 2-year
      follow-up showed a significantly lower incidence of MACE in DES patients (15.1
      vs. 24.2 vs. 20.8%, P = 0.001 for both), driven by a lower incidence of target
      lesion revascularization (8 vs. 14.6 vs. 13.9%, P = 0.002). Myocardial infarction
      rate was lower in the DES group as well (0.4 vs. 3.1% in BMS, P = 0.001). At
      multivariate analysis, BMS implantation and balloon angioplasty were independent
      predictors of long-term MACE. DES implantation was associated with a lower risk
      of long-term myocardial infarction [hazard ratio 0.15, 95% confidence interval
      (95% CI) 0.04-0.67] and target-lesion revascularization (hazard ratio 0.42, 95%
      CI 0.21-0.82). Male sex and DES use were independent predictors of the absence of
      MACE. CONCLUSION: After rotational atherectomy, DES implantation appears to be a
      preferable strategy, as it is associated with lower long-term MACE, despite an
      unexpected increase in periprocedural myocardial infarction.

PMID- 25575277
TI  - Bundle branch blocks and the risk of mortality in the Atherosclerosis Risk in
      Communities study.
AB  - AIMS: The main objective of our study was to evaluate the associations between
      different categories of bundle branch blocks (BBBs) and mortality and to consider
      possible impact of QRS prolongation in these associations. METHODS: This analysis
      included 15 408 participants (mean age 54 years, 55.2% women, and 26.9% blacks)
      from the Atherosclerosis Risk in Communities study. We used Cox regression to
      examine associations between left BBB (LBBB), right BBB (RBBB) and indetermined
      type of ventricular conduction defect [intraventricular conduction defect (IVCD)]
      with coronary heart disease (CHD) death and all-cause mortality. RESULTS: During
      a mean 21 years of follow-up, 4767 deaths occurred; of these, 728 were CHD
      deaths. Compared to No-BBB, LBBB and IVCD were strongly associated with increased
      CHD death (hazard ratios 4.11 and 3.18, respectively; P < 0.001 for both).
      Furthermore, compared to No-BBB with QRS duration less than 100 ms, CHD mortality
      risk was increased 1.33-fold for the No-BBB group with QRS duration 100-109 ms,
      and 1.48-fold with QRS duration 110-119 ms, 3.52-fold for pooled LBBB-IVCD group
      with QRS duration less than 140 ms and 4.96-fold for pooled LBBB-IVCD group with
      QRS duration at least 140 ms (P < 0.001). However, mortality risk was not
      significantly increased for lone RBBB. For all-cause mortality, trends similar to
      those for CHD death were observed within the BBB groups, although at lower levels
      of risk. CONCLUSION: Prevalent LBBB and IVCD, but not RBBB, are associated with
      increased risk of CHD death and all-cause mortality. Mortality risk is further
      increased as the QRS duration is prolonged above 140 ms.

PMID- 25575278
TI  - Non-valvular atrial fibrillation: potential clinical implications of the
      heterogeneous definitions used in trials on new oral anticoagulants.
AB  - AIMS: To evaluate the potential impact of the different definitions of non
      valvular atrial fibrillation reported in the literature and to analyse the
      possible implications for eligibility for novel oral anticoagulants (NOACs) in
      clinical practice. METHODS: We derived the definitions of 'non-valvular atrial
      fibrillation' from the exclusion criteria of the trials on NOACs, and then
      assessed the number and percentage of patients fulfilling the various definitions
      in a cohort of 500 consecutive atrial fibrillation patients, undergoing clinical
      and echocardiographic evaluation in our cardiology department, as either in
      patients or out-patients. RESULTS: Among the 500 atrial fibrillation patients
      (mean age 71.2 +/- 12.6 years), with permanent atrial fibrillation in 45.2% of
      the cases, hypertension was very common, either as the main diagnosis or as an
      associated disease. Valvular heart disease as the main diagnosis (including
      valvular prosthesis) accounted for 22.8% of the cases. At the echocardiographic
      evaluation, valvular alterations were very common, especially mitral
      regurgitation (present, with a variable degree of severity in 63.6% of the
      cases). Application of the RE-LY exclusion criteria with regard to valvular
      disease resulted in 116 (23.2%) patients of our cohort classified as valvular
      atrial fibrillation. This percentage was reduced to 12.2 and 8.8% if ROCKET-AF
      and ARISTOTLE/ENGAGE-AF criteria, respectively, were applied. CONCLUSIONS: Non
      valvular atrial fibrillation is a common clinical entity, but without a unified
      definition in the literature. The impact in daily practice of the different
      definitions adopted in trials is noteworthy, since in one patient out of seven,
      the eligibility for NOACs can be questioned, simply as a consequence of adopting
      a more or less restrictive definition.

PMID- 25575279
TI  - Massive left ventricular ischemia in a patient with anterior ST elevation
      myocardial infarction and anomalous origin of the circumflex artery.

PMID- 25575280
TI  - Induced rupture of vesicles adsorbed on glass by pore formation at the surface
      bilayer interface.
AB  - Supported lipid bilayers (SLBs) are often formed by spontaneous vesicle rupture
      and fusion on a solid surface. A well-characterized rupture mechanism for
      isolated vesicles is pore nucleation and expansion in the solution-exposed
      nonadsorbed area. In contrast, pore formation in the adsorbed bilayer region has
      not been investigated to date. In this work, we studied the detailed mechanisms
      of asymmetric rupture of giant unilamellar vesicles (GUVs) adsorbed on glass
      using fluorescence microscopy. Asymmetric rupture is the pathway where a rupture
      pore forms in a GUV near the edge of the glass-bilayer interface with high
      curvature and then expansion of the pore yields a planar bilayer patch. We show
      that asymmetric rupture occasionally resulted in SLB patches bearing a defect
      pore. The defect formation probability depended on lipid composition, salt
      concentration, and pH. Approximately 40% of negatively charged GUVs under
      physiological conditions formed pore-containing SLB patches, while negatively
      charged GUVs at low salt concentration or pH 4.0 and positively charged GUVs
      exhibited a low probability of defect inclusion. The edge of the defect pore was
      either in contact with (on-edge) or away from (off-edge) the edge of the planar
      bilayer. On-edge pores were predominantly formed over off-edge defects. Pores
      initially formed in the glass-adsorbed region before rupture, most frequently in
      close contact with the edge of the adsorbed region. When a pore formed near the
      edge of the adsorbed area or when the edge of a pore reached that of the adsorbed
      area by pore expansion, asymmetric rupture was induced from the defect site.
      These induced rupture mechanisms yielded SLB patches with an on-edge pore. In
      contrast, off-edge pores were produced when defect pore generation and subsequent
      vesicle rupture were uncoupled. The current results demonstrate that pore
      formation in the surface-adsorbed region of GUVs is not a negligible event. 

PMID- 25575281
TI  - An optimized platform for hydrophilic interaction chromatography-immobilized
      metal affinity chromatography enables deep coverage of the rat liver
      phosphoproteome.
AB  - While analysis of the phosphoproteome has become an important component of
      understanding how cells function, it remains a nontrivial task in terms of the
      number of sample preparation steps and instrument time needed to achieve
      sufficient depth of coverage to produce meaningful results. We previously
      described a multidimensional method that uses hydrophilic interaction
      chromatography (HILIC) followed by Fe(3+) immobilized metal affinity
      chromatography (IMAC) to reduce complexity, improve selectivity, and increase
      phosphopeptide identifications. Here we present refinements to our overall
      protocol that make it simpler and more efficient, while they provide greater
      coverage of the phosphoproteome. We introduce filter-aided sample prep (FASP) for
      cell lysis and trypsin digestion. Following HILIC separation, fractions are IMAC
      enriched using a 96-well filter plate. Finally, enriched samples are analyzed
      using an LC-MS strategy optimized for the fractionation scheme. The optimized
      protocol improves protein recovery, simplifies phosphopeptide enrichment, and
      optimizes instrument time, while it maintains deep coverage of the
      phosphoproteome. By using the refined protocol, we identified more than 16,000
      unique phosphosites from rat liver in a single experiment, which used
      approximately 1 day of instrument time. All together, we present evidence for
      24,485 rat liver phosphosites that represents the deepest coverage of a tissue
      phosphoproteome to date. 

PMID- 25575282
TI  - Cost-effectiveness of nitrogen mitigation by alternative household wastewater
      management technologies.
AB  - Household wastewater, especially from conventional septic systems, is a major
      contributor to nitrogen pollution. Alternative household wastewater management
      technologies provide similar sewerage management services but their life cycle
      costs and nitrogen flow implications remain uncertain. This paper addresses two
      key questions: (1) what are the total costs, nitrogen mitigation potential, and
      cost-effectiveness of a range of conventional and alternative municipal
      wastewater treatment technologies, and (2) what uncertainties influence these
      outcomes and how can we improve our understanding of these technologies? We
      estimate a household nitrogen mass balance for various household wastewater
      treatment systems and combine this mass balance with life cycle cost assessment
      to calculate the cost-effectiveness of nitrogen mitigation, which we define as
      nitrogen removed from the local watershed. We apply our methods to Falmouth, MA,
      where failing septic systems have caused heightened eutrophication in local
      receiving water bodies. We find that flushing and dry (composting) urine
      diversion toilets paired with conventional septic systems for greywater
      management demonstrate the lowest life cycle cost and highest cost-effectiveness
      (dollars per kilogram of nitrogen removed from the watershed). Composting toilets
      are also attractive options in some cases, particularly best-case nitrogen
      mitigation. Innovative/advanced septic systems designed for high-level nitrogen
      removal are cost-competitive options for newly constructed homes, except at their
      most expensive. A centralized wastewater treatment plant is the most expensive
      and least cost-effective option in all cases. Using a greywater recycling system
      with any treatment technology increases the cost without adding any nitrogen
      removal benefits. Sensitivity analysis shows that these results are robust
      considering a range of cases and uncertainties. 

PMID- 25575283
TI  - Explorative function in Prader-Willi syndrome analyzed through an ecological
      spatial task.
AB  - This study was aimed at evaluating the spatial abilities in individuals with
      Prader-Willi syndrome (PWS) by using an ecological large-scale task with multiple
      rewards. To evaluate the extent of spatial deficit in PWS individuals, we compare
      their performances with those of individuals with Williams Syndrome (WS) in which
      the spatial deficits have been widely described. Participants had to explore an
      open space to search nine rewards placed in buckets arranged according to three
      spatial configurations: a Cross, a 3*3 Matrix and a Cluster composed by three
      groups of three buckets each. PWS individuals exhibited an explorative deficit in
      Cluster and Cross configurations, while WS participants in Matrix and Cross
      configurations. The findings indicate that the structural affordances of the
      environment influence the explorative strategies and can be related to how
      spatial information is processed. 

PMID- 25575284
TI  - A comparative study of sensory processing in children with and without Autism
      Spectrum Disorder in the home and classroom environments.
AB  - Sensory processing and higher integrative functions impairments are highly
      prevalent in children with ASD. Context should be considered in analyzing the
      sensory profile and higher integrative functions. The main objective of this
      study is to compare sensory processing, social participation and praxis in a
      group of 79 children (65 males and 14 females) from 5 to 8 years of age (M=6.09)
      divided into two groups: ASD Group (n=41) and Comparison Group (n=38). The
      Sensory Processing Measure (SPM) was used to evaluate the sensory profile of the
      children: parents reported information about their children's characteristics in
      the home environment, and teachers reported information about the same
      characteristics in the classroom environment. The ASD Group obtained scores that
      indicate higher levels of dysfunction on all the assessed measures in both
      environments, with the greatest differences obtained on the social participation
      and praxis variables. The most affected sensory modalities in the ASD Group were
      hearing and touch. Only in the ASD Group were significant differences found
      between the information reported by parents and what was reported by teachers:
      specifically, the teachers reported greater dysfunction than the parents in
      social participation (p=.000), touch (p=.003) and praxis (p=.010). These results
      suggest that the context-specific qualities found in children with ASD point out
      the need to receive information from both parents and teachers during the sensory
      profile assessment process, and use context-specific assessments. 

PMID- 25575285
TI  - Short-term motor learning of dynamic balance control in children with probable
      Developmental Coordination Disorder.
AB  - PURPOSE: To explore the differences in learning a dynamic balance task between
      children with and without probable Developmental Coordination Disorder (p-DCD)
      from different cultural backgrounds. PARTICIPANTS: Twenty-eight Dutch children
      with DCD (p-DCD-NL), a similar group of 17 South African children (p-DCD-SA) and
      21 Dutch typically developing children (TD-NL) participated in the study.
      METHODS: All children performed the Wii Fit protocol. The slope of the learning
      curve was used to estimate motor learning for each group. The protocol was
      repeated after six weeks. Level of motor skill was assessed with the Movement ABC
      2. RESULTS: No significant difference in motor learning rate was found between p
      DCD-NL and p-DCD-SA, but the learning rate of children with p-DCD was slower than
      the learning rate of TD children. Speed-accuracy trade off, as a way to improve
      performance by slowing down in the beginning was only seen in the TD children,
      indicating that TD children and p-DCD children used different strategies.
      Retention of the level of learned control of the game after six weeks was found
      in all three groups after six weeks. The learning slope was associated with the
      level of balance skill for all children. This study provides evidence that
      children with p-DCD have limitations in motor learning on a complex balance task.
      In addition, the data do not support the contention that learning in DCD differs
      depending on cultural background.

PMID- 25575286
TI  - Uncovering the evidence for behavioral interventions with individuals with
      fragile X syndrome: a systematic review.
AB  - Fragile X syndrome (FXS) is associated with a wide range of cognitive, emotional,
      and behavioral difficulties. Although there is considerable research on the
      behavioral phenotype of FXS, few empirical studies of behavioral interventions
      with this population have been identified. Through a hand search of 34 behavioral
      journals, we examined the evidence base for behavioral interventions with
      individuals with FXS and in light of the current state of knowledge regarding the
      FXS behavioral phenotype. Systematic review procedures were used to identify
      behavioral intervention studies that included at least one participant with FXS,
      extract and summarize the data on several relevant dimensions, and rate the
      methodological quality of the studies. Results revealed 31 intervention studies
      with a small number of participants with FXS. Overall, results suggest a
      behavioral approach to intervention with individuals with FXS shows promise.
      Future research focused on individuals with FXS will be necessary to continue to
      examine differences in response to intervention and interventions that
      specifically address phenotypic characteristics. 

PMID- 25575287
TI  - Acute behavioral crises in psychiatric inpatients with autism spectrum disorder
      (ASD): recognition of concomitant medical or non-ASD psychiatric conditions
      predicts enhanced improvement.
AB  - During adolescence, some individuals with autism spectrum disorder (ASD) engage
      in severe challenging behaviors, such as aggression, self-injury, disruption,
      agitation and tantrums. We aimed to assess risk factors associated with very
      acute behavioral crises in adolescents with ASD admitted to a dedicated
      neurobehavioral unit. We included retrospectively in 2008 and 2009 29 adolescents
      and young adults with ASD hospitalized for severe challenging behaviors and
      proposed a guideline (Perisse et al., 2010) that we applied prospectively for 29
      patients recruited for the same indications between 2010 and 2012. In total, 58
      patients were admitted (n=70 hospitalizations, mean age=15.66 (+/-4.07) years,
      76% male). We systematically collected data describing socio-demographic
      characteristics, clinical variables (severity, presence of language, cognitive
      level), comorbid organic conditions, etiologic diagnosis of the episode, and
      treatments. We explored predictors of Global Assessment Functioning Scale (GAFS)
      score and duration of hospitalization at discharge. All but 2 patients exhibited
      severe autistic symptoms and intellectual disability (ID), and two-thirds had no
      functional verbal language. During the inpatient stay (mean=84.3 (+/-94.9) days),
      patients doubled on average their GAFS scores (mean=17.66 (+/-9.05) at admission
      vs. mean=31.4 (+/-9.48) at discharge). Most common etiologies for acute
      behavioral crises were organic causes [n=20 (28%), including epilepsy: n=10 (14%)
      and painful medical conditions: n=10 (14%)], environmental causes [n=17 (25%)
      including lack of treatment: n=11 (16%) and adjustment disorder: n=6 (9%)], and
      non-ASD psychiatric condition [n=33 (48%) including catatonia: n=5 (7%), major
      depressive episode: n=6 (9%), bipolar disorder: n=4 (6%), schizophrenia: n=6
      (9%), other/unknown diagnosis: n=12 (17%)]. We found no influence of age, gender,
      socio-economic status, migration, level of ID, or history of seizure on
      improvement of GAFS score at discharge. Severity of autism at admission was the
      only negative predictor (p<.001). Painful medical conditions (p=.04), non-ASD
      psychiatric diagnoses (p=.001), prior usage of specialized ASD care programs
      (p=.004), functional language (p=.007), as well as a higher number of challenging
      behaviors upon admission (p=.001) were associated with higher GAFS scores at
      discharge. Clinical severity at admission, based on the number of challenging
      behaviors (r=.35, p=.003) and GAFS score (r=-.32, p=.008) was correlated with a
      longer inpatient stay. Longer hospitalization was however correlated (r=.27,
      p=.03) with higher GAFS score at discharge even after adjustment for confounding
      factors. Challenging behaviors among adolescents with ASD may stem from diverse
      risk factors, including environmental problems, comorbid acute psychiatric
      conditions, or somatic illness such as epilepsy or acute pain. The management of
      these behavioral challenges requires a unified, multidisciplinary approach. 

PMID- 25575288
TI  - Effects of an eight-week whole body vibration on lower extremity muscle tone and
      function in children with cerebral palsy.
AB  - The aim of this study was to evaluate the effect of an eight-week whole body
      vibration (WBV) on lower extremity spasticity and ambulatory function in children
      with cerebral palsy with a complete crossover design. Sixteen participants aged
      9.2 (2.1) years participated in this study. Half of the participants received a
      10-min WBV, 3 times a week for 8 weeks. Then a 4-week washout period followed,
      after which they received a sham WBV 3 times a week for 8 weeks. The other half
      received the intervention in a reversed order. The participants were evaluated
      via variables measuring range-of-motion, muscle tone, and ambulatory function
      before, immediately after, 1 day after, and 3 days after each intervention.
      Repeated-measures analyses revealed significant beneficial effects on most
      variables expect the passive range-of-motion measurement. Significant
      correlations were found between timed up-and-go and relaxation index, and between
      timed up-and-go and six-minute walk test. The results suggested that an 8-week
      WBV intervention normalized muscle tone, improved active joint range and enhanced
      ambulatory performance in children with cerebral palsy for at least 3 days. These
      indicated that regular WBV can serve as an alternative, safe, and efficient
      treatment for these children in both clinical and home settings. 

PMID- 25575289
TI  - Public stigma and the perception of rights: differences between intellectual and
      physical disabilities.
AB  - Stigma may have detrimental effects on the rights of individuals with
      disabilities. This study examined the association between stigma and the
      perception of rights of people with intellectual disabilities and people with
      physical disabilities. Telephone interviews using vignette methodology were
      conducted with a nationally representative sample of 605 adults. Items included
      stereotypes, prejudice, behavioral reactions and the perception of rights of
      these individuals. More negative stereotypes, greater social distance and greater
      withdrawal behaviors were found toward people with intellectual disabilities as
      compared to people with physical disabilities. Lower support of rights was found
      toward people with intellectual disabilities as compared to people with physical
      disabilities. Lower degree of acceptance and higher perception of dangerousness
      were associated with greater social distance, which was related to lower
      perception of rights. Programs should aim at decreasing social distance to
      improve support to exercise rights, especially among people with intellectual
      disabilities. 

PMID- 25575293
TI  - The effects of globotriaosylceramide tail saturation level on bilayer phases.
AB  - Globotriaosylceramide (Gb3) is a glycosphingolipid present in the plasma membrane
      that is the natural receptor of the bacterial Shiga toxin. The unsaturation level
      of Gb3 acyl chains has a drastic impact on lipid bilayer properties and phase
      behaviour, and on many Gb3-related cellular processes. For example: the Shiga
      toxin B subunit forms tubular invaginations in the presence of Gb3 with an
      unsaturated acyl chain (U-Gb3), while in the presence of Gb3 with a saturated
      acyl chain (S-Gb3) such invagination does not occur. We have used all-atom
      molecular dynamics simulations to investigate the effects of the Gb3
      concentration and its acyl chain saturation on the phase behaviour of a mixed
      bilayer of dioleoylphosphatidylcholine and Gb3. The simulation results show that:
      (1) the Gb3 acyl chains (longer tails) from one leaflet interdigitate into the
      opposing leaflet and lead to significant bilayer rigidification and
      immobilisation of the lipid tails. S-Gb3 can form a highly ordered, relatively
      immobile phase which is resistant to bending while these changes for U-Gb3 are
      not significant. (2) At low concentrations of Gb3, U-Gb3 and S-Gb3 have a similar
      impact on the bilayer reminiscent of the effect of sphingomyelin lipids and (3)
      At higher Gb3 concentrations, U-Gb3 mixes better with dioleoylphosphatidylcholine
      than S-Gb3. Our simulations also provide the first molecular level structural
      model of Gb3 in membranes. 

PMID- 25575291
TI  - Organochlorine and organophosphorus pesticide residues in raw buffalo milk from
      agroindustrial areas in Assiut, Egypt.
AB  - Raw buffalo milk samples from the agroindustrial zone in upper Egypt were
      analyzed for the presence of organochlorine and organophosphorus pesticides using
      gas chromatography-mass spectroscopy. Five organochlorine pesticides namely,
      alachlor, dieldrin, hexachlorobenzene, lindane and methoxychlor and three
      organophosphorus pesticides chlorpyrifos, malathion, and parathion-methyl were
      detected in the milk samples. In 44% of the samples, the concentrations of
      lindane and malathion residues exceeded tolerance levels set by the European
      Commission (EC) in 2008. In addition, the concentrations of chlorpyrifos,
      methoxychlor, and hexachlorobenzene residues exceeded the 2008 EC maximum
      residual limits (MRLs) by 33, 66, and 88% of the examined samples, respectively.
      However, the levels of alachlor, dieldrin, and parathion-methyl residues were
      below EC MRLs. The results of this study confirm the risks of pesticide residues
      exposure that threaten consumer health in Egypt. Thus, we recommend that
      pesticide residue monitoring programs be instituted in all the developing
      countries. 

PMID- 25575294
TI  - The smallest resonator arrays in atmosphere by chip-size-grown nanowires with
      tunable Q-factor and frequency for subnanometer thickness detection.
AB  - A chip-size vertically aligned nanowire (NW) resonator arrays (VNRs) device has
      been fabricated with simple one-step lithography process by using grown self
      assembled zinc oxide (ZnO) NW arrays. VNR has cantilever diameter of 50 nm, which
      breakthroughs smallest resonator record (>100 nm) functioning in atmosphere. A
      new atomic displacement sensing method by using atomic force microscopy is
      developed to effectively identify the resonance of NW resonator with diameter 50
      nm in atmosphere. Size-effect and half-dimensional properties of the NW resonator
      have been systematically studied. Additionally, VNR has been demonstrated with
      the ability of detecting nanofilm thickness with subnanometer (<10(-9)m)
      resolution. 

PMID- 25575295
TI  - A Comparison of Pain Assessment Measures in Pediatric Sickle Cell Disease: Visual
      Analog Scale Versus Numeric Rating Scale.
AB  - Given the availability of various pain severity scales, greater understanding of
      the agreement between pain scales is warranted. We compared Visual Analog Scale
      (VAS) and Numeric Rating Scale (NRS) pain severity ratings in children with
      sickle cell disease (SCD) to identify the relationship and agreement between pain
      scale ratings. Twenty-eight patients (mean +/- SD age, 14.65 +/- 3.12 y, 50%
      female) receiving pain interventions within the emergency department completed
      serial VAS and NRS pain severity ratings every 30 minutes. Data were used to
      calculate the relationship (Spearman correlation) and agreement (Bland-Altman
      approach) between the VAS and NRS. One hundred twenty-eight paired VAS-NRS
      measurements were obtained. VAS and NRS ratings were significantly correlated for
      the initial assessment (rs = 0.88, P < 0.001) and all assessments (rs = 0.87, P <
      0.001). Differences between VAS and NRS means were -0.52 (P = 0.006) for the
      initial assessment and -0.86 (P < 0.001) across all assessments. The difference
      between VAS and NRS ratings decreased as pain severity increased across all
      assessments (P = 0.027), but not the initial assessment. Within pediatric
      patients with SCD, VAS and NRS ratings were found to trend together; however, VAS
      scores were found to be significantly lower than NRS scores across assessments.
      The agreement between the 2 measures improved at increasing levels of pain
      severity. These findings demonstrate that the VAS and NRS are similar, but cannot
      be used interchangeably when assessing self-reported pain in SCD.

PMID- 25575296
TI  - Differentiated embryonic chondrocytes 1 expression of periodontal ligament tissue
      and gingival tissue in the patients with chronic periodontitis.
AB  - OBJECTIVE: To evaluate the DEC1 expression of periodontal ligament tissue and
      gingival tissue in the patients with chronic periodontitis. METHODS: 20 non
      smoking patients with chronic periodontitis and 20 healthy individuals were
      enrolled. Periodontal ligament tissue and gingival tissue samples from healthy
      subjects were collected during teeth extraction for orthodontic reason or the
      third molar extraction. The parallel samples from patients with chronic
      periodontitis were obtained during periodontal flap operations or teeth
      extraction as part of periodontal treatment. The DEC1 expression and the alkaline
      phosphatase (ALP) activity of both the periodontal ligament tissue and gingival
      tissue were determined by Western blot, Immunohistochemistry and ALP Detection
      Kit. RESULTS: The DEC1 expression of periodontal ligament tissue in the patients
      with chronic periodontitis decreased significantly along with the decreased ALP
      activity. On the contrary, the DEC1 expression of gingival tissue in the patients
      with chronic periodontitis increased significantly. Further study found that the
      DEC1 expression of gingival tissue increased mainly in the suprabasal layer of
      gingival epithelial cells but decreased in the gingival connective tissue of the
      patients with chronic periodontitis. CONCLUSION: The DEC1 expression decreases in
      the periodontal ligament tissue which is related to the osteogenic capacity,
      whereas the DEC1 expression increases in the suprabasal layer of gingival
      epithelial cells which are involved in immune inflammatory response in the
      patients with chronic periodontitis. The findings provide a new target to explore
      the pathology and the therapy of periodontitis.

PMID- 25575297
TI  - Induction of IL-6 and IL-8 by activation of thermosensitive TRP channels in human
      PDL cells.
AB  - OBJECTIVE: The oral cavity is often exposed to not only diverse external
      pathogens but also dramatic temperature changes. In this study, we investigated
      the effect of thermal stress on PDL cells with a focus on the inflammatory
      responses and bone homeostasis. DESIGN: The PDL cells were isolated from healthy
      premolar extracted for orthodontic reasons, and examined using intracellular
      calcium concentration ([Ca(2+)]i) measurement and reverse transcription
      polymerase chain reaction for pro-inflammatory cytokines and bone remodelling
      mediators. RESULTS: We detected the expression of thermosensitive transient
      receptor potential (TRP) channels, such as TRPV1, TRPV2, TRPV3, TRPM8, and TRPA1.
      Functional activation of the channels by thermal stress and their specific
      agonists increased [Ca(2+)]i and interleukin (IL)-6 and IL-8 mRNA expression. A
      selective Ca(2+) chelator, BAPTA-AM, prevented TRP channel agonists-mediated IL-6
      and IL-8 induction. Unlike pro-inflammatory cytokines, the expression of bone
      remodelling mediators, including receptor activator of nuclear factor-kappa B
      ligand and osteoprotegerin, was not altered by treatment with TRP channel
      agonists. CONCLUSIONS: The activation of thermosensitive TRP channels induced IL
      6 and IL-8 expression by increasing [Ca(2+)]i in human PDL cells. Therefore,
      thermal stress may play a critical role in the inflammatory responses of PDL
      cells.

PMID- 25575298
TI  - The role of cilia in the pathogenesis of cystic kidney disease.
AB  - PURPOSE OF REVIEW: Primary (immotile) cilia are specialized organelles present on
      most cell types. Almost all of proteins associated with a broad spectrum of human
      cystic kidney diseases have been localized to the region in or around the cilia.
      Abnormal cilia structure and function have both been reported in animal models
      and human cystic kidneys. The goal of this review is to discuss current
      understanding of the mechanisms by which abnormal genes/proteins and cilia
      interact to potentially influence renal cystogenesis. RECENT FINDINGS: Novel
      direct recording of cilia calcium levels/channel activity suggests that cilia
      form a calcium-mediated signaling microenvironment separate from the cytoplasm,
      which could provide a mechanism for cilia-specific downstream signaling. Genetic
      based studies confirm that cilia are not required for cystogenesis, but modulate
      cystic kidney disease severity through a novel, undefined mechanism. Mechanisms
      by which both cilia-associated and noncilia-associated proteins can alter cilia
      structure/function have also been identified. SUMMARY: Considerable progress has
      been made in defining the mechanisms by which abnormal genes and proteins affect
      cilia structure and function. However, the exact mechanisms by which these
      interactions cause renal cyst formation and progression of cystic kidney disease
      are still unknown.

PMID- 25575300
TI  - Fixed distance photoinduced electron transfer between Fe and Zn porphyrins
      encapsulated within the Zn HKUST-1 metal organic framework.
AB  - An attractive strategy for the development of photocatalytic metal organic
      framework (MOF) materials is to co-encapsulate a photoactive electron donor with
      a catalytic electron acceptor within the MOF. Here we report the co-encapsulation
      of both Zn(ii) tetrakis(tetra 4-sulphonatophenyl)porphyrin (Zn4SP) and Fe(iii)
      tetrakis(tetra 4-sulphonatophenyl)porphyrin (Fe4SP) into an HKUST-1 (Zn) MOF and
      demonstrate photoinduced electron transfer (ET) between the co-encapsulated
      guest. Photo-excitation of the Zn4SP results in fixed-distance inter-molecular ET
      between the encapsulated (3)Zn4SP and the Fe(iii)4SP as evident by the reduction
      in the encapsulated (3)Zn4SP lifetime from 890 MUs (kobs = 1.1 * 10(3) s(-1)) to
      83 MUs (kobs = 1.2 * 10(4) s(-1)) in the presence of Fe4SP giving a kET ~ 1.1 *
      10(4) s(-1). The data are consistent with ET taking place between encapsulated
      porphyrins that are two cages apart in distance with a reorganizational energy of
      ~1.65 eV, beta = 1.25 and DeltaG degrees  = -0.97 eV (within a semi-classical
      Marcus theory framework). 

PMID- 25575299
TI  - Bifunctional fatty acid chemical reporter for analyzing S-palmitoylated membrane
      protein-protein interactions in mammalian cells.
AB  - Studying the functions of S-palmitoylated proteins in cells can be challenging
      due to the membrane targeting property and dynamic nature of protein S
      palmitoylation. New strategies are therefore needed to specifically capture S
      palmitoylated protein complexes in cellular membranes for dissecting their
      functions in vivo. Here we present a bifunctional fatty acid chemical reporter, x
      alk-16, which contains an alkyne and a diazirine, for metabolic labeling of S
      palmitoylated proteins and photo-cross-linking of their involved protein
      complexes in mammalian cells. We demonstrate that x-alk-16 can be metabolically
      incorporated into known S-palmitoylated proteins such as H-Ras and IFITM3, a
      potent antiviral protein, and induce covalent cross-linking of IFITM3
      oligomerization as well as its specific interactions with other membrane proteins
      upon in-cell photoactivation. Moreover, integration of x-alk-16-induced photo
      cross-linking with label-free quantitative proteomics allows identification of
      new IFITM3 interacting proteins. 

PMID- 25575301
TI  - The state of economic evaluation in vision research--adding a fourth for bridge.

PMID- 25575290
TI  - New facets in the regulation of gene expression by ADP-ribosylation and poly(ADP
      ribose) polymerases.

PMID- 25575302
TI  - The roles of akt isoforms in the regulation of podosome formation in fibroblasts
      and extracellular matrix invasion.
AB  - Mesenchymal cells employ actin-based membrane protrusions called podosomes and
      invadopodia for cross-tissue migration during normal human development such as
      embryogenesis and angiogenesis, and in diseases such as atherosclerosis plaque
      formation and cancer cell metastasis. The Akt isoforms, downstream effectors of
      phosphatidylinositol 3 kinase (PI3K), play crucial roles in cell migration and
      invasion, but their involvement in podosome formation and cell invasion is not
      known. In this study, we have used Akt1 and/or Akt2 knockout mouse embryonic
      fibroblasts and Akt3-targeted shRNA to determine the roles of the three Akt
      isoforms in Src and phorbol ester-induced podosome formation, and extracellular
      matrix (ECM) digestion. We found that deletion or knockdown of Akt1 significantly
      reduces Src-induced formation of podosomes and rosettes, and ECM digestion, while
      suppression of Akt2 has little effect. In contrast, Akt3 knockdown by shRNA
      increases Src-induced podosome/rosette formation and ECM invasion. These data
      suggest that Akt1 promotes, while Akt3 suppresses, podosome formation induced by
      Src, and Akt2 appears to play an insignificant role. Interestingly, both Akt1 and
      Akt3 suppress, while Akt2 enhances, phorbol ester-induced podosome formation.
      These data show that Akt1, Akt2 and Akt3 play different roles in podosome
      formation and ECM invasion induced by Src or phorbol ester, thus underscoring the
      importance of cell context in the roles of Akt isoforms in cell invasion. 

PMID- 25575304
TI  - Prospects of molybdenum and rhenium octahedral cluster complexes as X-ray
      contrast agents.
AB  - Investigation of new X-ray contrast media for radiography is an important field
      of science since discovering of X-rays in 1895. Despite the wide diversity of
      available X-ray contrast media the toxicity, especially nephrotoxicity, is still
      a big problem to be solved. The octahedral metal-cluster complexes of the general
      formula [{M6Q8}L6] can be considered as quite promising candidates for the role
      of new radiocontrast media due to the high local concentration of heavy elements,
      high tuning ability of ligand environment and low toxicity. To exemplify this,
      the X-ray computed tomography experiments for the first time were carried out on
      some octahedral cluster complexes of molybdenum and rhenium. Based on the
      obtained data it was proposed to investigate the toxicological proprieties of
      cluster complex Na2H8[{Re6Se8}(P(CH2CH2CONH2)(CH2CH2COO)2)6]. Observed low
      cytotoxic and acute toxic effects along with rapid renal excretion of the cluster
      complex evidence its perspective as an X-ray contrast media for radiography. 

PMID- 25575303
TI  - Evaluation of the cell cytotoxicity and DNA/BSA binding and cleavage activity of
      some dioxidovanadium(V) complexes containing aroylhydrazones.
AB  - Three dioxidovanadium(V) complexes [VO2L(1-3)] (1-3) [HL(1)=1-napthoyl hydrazone
      of 2-acetyl pyridine, HL(2)=2-furoyl hydrazone of 2-acetyl pyridine and
      H2L(3)=isonicotinoyl hydrazone of 2-hydroxy benzaldehyde] have been reported. All
      the complexes were characterized by various spectroscopy (IR, UV-visible and NMR)
      and the molecular structures of 1 and 2 were characterized by single crystal X
      ray diffraction technique. Structural report established five-coordinate
      geometries, distorted toward square pyramidal for each of 1 and 2, based on a
      tridentate -O,N,N coordinating anion and two oxido-O atoms. The experimental
      results show that the complexes interact with calf-thymus DNA (CT-DNA) possibly
      by a groove binding mode, with binding constants of ~10(5)M(-1). All complexes
      show good photo-induced cleavage of pUC19 supercoiled plasmid DNA with complex 1
      showing the highest photo-induced DNA cleavage activity of ~68%. 1-3 also exhibit
      moderate binding affinity in the range of 10(3)-10(4)M(-1) towards bovine serum
      albumin (BSA), while all the complexes show good photo-induced BSA cleavage
      activity. Moreover the antiproliferative activity of all these complexes was
      studied, which reveal all compounds are significantly cytotoxic towards the HeLa
      cell line. 

PMID- 25575305
TI  - The physiology and ecological implications of efficient growth.
AB  - The natural habitats of microbes are typically spatially structured with limited
      resources, so opportunities for unconstrained, balanced growth are rare. In these
      habitats, selection should favor microbes that are able to use resources most
      efficiently, that is, microbes that produce the most progeny per unit of resource
      consumed. On the basis of this assertion, we propose that selection for
      efficiency is a primary driver of the composition of microbial communities. In
      this article, we review how the quality and quantity of resources influence the
      efficiency of heterotrophic growth. A conceptual model proposing innate
      differences in growth efficiency between oligotrophic and copiotrophic microbes
      is also provided. We conclude that elucidation of the mechanisms underlying
      efficient growth will enhance our understanding of the selective pressures
      shaping microbes and will improve our capacity to manage microbial communities
      effectively. 

PMID- 25575306
TI  - Aerobic and anaerobic nitrogen transformation processes in N2-fixing
      cyanobacterial aggregates.
AB  - Colonies of N(2)-fixing cyanobacteria are key players in supplying new nitrogen
      to the ocean, but the biological fate of this fixed nitrogen remains poorly
      constrained. Here, we report on aerobic and anaerobic microbial nitrogen
      transformation processes that co-occur within millimetre-sized cyanobacterial
      aggregates (Nodularia spumigena) collected in aerated surface waters in the
      Baltic Sea. Microelectrode profiles showed steep oxygen gradients inside the
      aggregates and the potential for nitrous oxide production in the aggregates'
      anoxic centres. (15)N-isotope labelling experiments and nutrient analyses
      revealed that N(2) fixation, ammonification, nitrification, nitrate reduction to
      ammonium, denitrification and possibly anaerobic ammonium oxidation (anammox) can
      co-occur within these consortia. Thus, N. spumigena aggregates are potential
      sites of nitrogen gain, recycling and loss. Rates of nitrate reduction to
      ammonium and N(2) were limited by low internal nitrification rates and low
      concentrations of nitrate in the ambient water. Presumably, patterns of N
      transformation processes similar to those observed in this study arise also in
      other phytoplankton colonies, marine snow and fecal pellets. Anoxic microniches,
      as a pre-condition for anaerobic nitrogen transformations, may occur within large
      aggregates (?1 mm) even when suspended in fully oxygenated waters, whereas anoxia
      in small aggregates (<1 to ?0.1 mm) may only arise in low-oxygenated waters (?25
      MUM). We propose that the net effect of aggregates on nitrogen loss is negligible
      in NO(3)(-)-depleted, fully oxygenated (surface) waters. In NO(3)(-)-enriched
      (>1.5 MUM), O(2)-depleted water layers, for example, in the chemocline of the
      Baltic Sea or the oceanic mesopelagic zone, aggregates may promote N-recycling
      and -loss processes.

PMID- 25575307
TI  - Connecting biodiversity and potential functional role in modern euxinic
      environments by microbial metagenomics.
AB  - Stratified sulfurous lakes are appropriate environments for studying the links
      between composition and functionality in microbial communities and are
      potentially modern analogs of anoxic conditions prevailing in the ancient ocean.
      We explored these aspects in the Lake Banyoles karstic area (NE Spain) through
      metagenomics and in silico reconstruction of carbon, nitrogen and sulfur
      metabolic pathways that were tightly coupled through a few bacterial groups. The
      potential for nitrogen fixation and denitrification was detected in both
      autotrophs and heterotrophs, with a major role for nitrogen and carbon fixations
      in Chlorobiaceae. Campylobacterales accounted for a large percentage of
      denitrification genes, while Gallionellales were putatively involved in
      denitrification, iron oxidation and carbon fixation and may have a major role in
      the biogeochemistry of the iron cycle. Bacteroidales were also abundant and
      showed potential for dissimilatory nitrate reduction to ammonium. The very low
      abundance of genes for nitrification, the minor presence of anammox genes, the
      high potential for nitrogen fixation and mineralization and the potential for
      chemotrophic CO2 fixation and CO oxidation all provide potential clues on the
      anoxic zones functioning. We observed higher gene abundance of ammonia-oxidizing
      bacteria than ammonia-oxidizing archaea that may have a geochemical and
      evolutionary link related to the dominance of Fe in these environments. Overall,
      these results offer a more detailed perspective on the microbial ecology of
      anoxic environments and may help to develop new geochemical proxies to infer
      biology and chemistry interactions in ancient ecosystems. 

PMID- 25575308
TI  - Diverse protist grazers select for virulence-related traits in Legionella.
AB  - It is generally accepted that selection for resistance to grazing by protists has
      contributed to the evolution of Legionella pneumophila as a pathogen. Grazing
      resistance is becoming more generally recognized as having an important role in
      the ecology and evolution of bacterial pathogenesis. However, selection for
      grazing resistance presupposes the existence of protist grazers that provide the
      selective pressure. To determine whether there are protists that graze on
      pathogenic Legionella species, we investigated the existence of such organisms in
      a variety of environmental samples. We isolated and characterized diverse
      protists that graze on L. pneumophila and determined the effects of adding L.
      pneumophila on the protist community structures in microcosms made from these
      environmental samples. Several unrelated organisms were able to graze efficiently
      on L. pneumophila. The community structures of all samples were markedly altered
      by the addition of L. pneumophila. Surprisingly, some of the Legionella grazers
      were closely related to species that are known hosts for L. pneumophila,
      indicating the presence of unknown specificity determinants for this interaction.
      These results provide the first direct support for the hypothesis that protist
      grazers exert selective pressure on Legionella to acquire and retain adaptations
      that contribute to survival, and that these properties are relevant to the
      ability of the bacteria to cause disease in people. We also report a novel
      mechanism of killing of amoebae by one Legionella species that requires an intact
      Type IV secretion system but does not involve intracellular replication. We refer
      to this phenomenon as 'food poisoning'. 

PMID- 25575309
TI  - Energy landscapes shape microbial communities in hydrothermal systems on the
      Arctic Mid-Ocean Ridge.
AB  - Methods developed in geochemical modelling combined with recent advances in
      molecular microbial ecology provide new opportunities to explore how microbial
      communities are shaped by their chemical surroundings. Here, we present a
      framework for analyses of how chemical energy availability shape chemotrophic
      microbial communities in hydrothermal systems through an investigation of two
      geochemically different basalt-hosted hydrothermal systems on the Arctic Mid
      Ocean Ridge: the Soria Moria Vent field (SMVF) and the Loki's Castle Vent Field
      (LCVF). Chemical energy landscapes were evaluated through modelling of the Gibbs
      energy from selected redox reactions under different mixing ratios between
      seawater and hydrothermal fluids. Our models indicate that the sediment
      influenced LCVF has a much higher potential for both anaerobic and aerobic
      methane oxidation, as well as aerobic ammonium and hydrogen oxidation, than the
      SMVF. The modelled energy landscapes were used to develop microbial community
      composition models, which were compared with community compositions in
      environmental samples inside or on the exterior of hydrothermal chimneys, as
      assessed by pyrosequencing of partial 16S rRNA genes. We show that modelled
      microbial communities based solely on thermodynamic considerations can have a
      high predictive power and provide a framework for analyses of the link between
      energy availability and microbial community composition. 

PMID- 25575310
TI  - Similarities and seasonal variations in bacterial communities from the blood of
      rodents and from their flea vectors.
AB  - Vector-borne microbes are subject to the ecological constraints of two distinct
      microenvironments: that in the arthropod vector and that in the blood of its
      vertebrate host. Because the structure of bacterial communities in these two
      microenvironments may substantially affect the abundance of vector-borne
      microbes, it is important to understand the relationship between bacterial
      communities in both microenvironments and the determinants that shape them. We
      used pyrosequencing analyses to compare the structure of bacterial communities in
      Synosternus cleopatrae fleas and in the blood of their Gerbillus andersoni hosts.
      We also monitored the interindividual and seasonal variability in these bacterial
      communities by sampling the same individual wild rodents during the spring and
      again during the summer. We show that the bacterial communities in each sample
      type (blood, female flea or male flea) had a similar phylotype composition among
      host individuals, but exhibited seasonal variability that was not directly
      associated with host characteristics. The structure of bacterial communities in
      male fleas and in the blood of their rodent hosts was remarkably similar and was
      dominated by flea-borne Bartonella and Mycoplasma phylotypes. A lower abundance
      of flea-borne bacteria and the presence of Wolbachia phylotypes distinguished
      bacterial communities in female fleas from those in male fleas and in rodent
      blood. These results suggest that the overall abundance of a certain vector-borne
      microbe is more likely to be determined by the abundance of endosymbiotic
      bacteria in the vector, abundance of other vector-borne microbes co-occurring in
      the vector and in the host blood and by seasonal changes, than by host
      characteristics. 

PMID- 25575315
TI  - Structures of tetrasilylmethane derivatives (XMe2Si)2C(SiMe3)2 (X = H, Cl, Br) in
      the gas phase, and their dynamic structures in solution.
AB  - The structures of the molecules (XMe2Si)2C(SiMe3)2, where X = H, Cl, Br, have
      been determined by gas electron diffraction (GED) using the SARACEN method of
      restraints, with all analogues existing in the gas phase as mixtures of C1- and
      C2-symmetric conformers. Variable temperature (1)H and (29)Si solution-phase NMR
      studies, as well as (13)C NMR and (1)H/(29)Si NMR shift correlation and (1)H NMR
      saturation transfer experiments for the chlorine and bromine analogues, are
      reported. At low temperatures in solution there appear to be two C1 conformers
      and two C2 conformers, agreeing with the isolated-molecule calculations used to
      guide the electron diffraction refinements. For (HMe2Si)2C(SiMe3)2 the
      calculations indicated six conformers close in energy, and these were modeled in
      the GED refinement. 

PMID- 25575311
TI  - Divergence across diet, time and populations rules out parallel evolution in the
      gut microbiomes of Trinidadian guppies.
AB  - Diverse microbial consortia profoundly influence animal biology, necessitating an
      understanding of microbiome variation in studies of animal adaptation. Yet,
      little is known about such variability among fish, in spite of their importance
      in aquatic ecosystems. The Trinidadian guppy, Poecilia reticulata, is an
      intriguing candidate to test microbiome-related hypotheses on the drivers and
      consequences of animal adaptation, given the recent parallel origins of a similar
      ecotype across streams. To assess the relationships between the microbiome and
      host adaptation, we used 16S rRNA amplicon sequencing to characterize gut
      bacteria of two guppy ecotypes with known divergence in diet, life history,
      physiology and morphology collected from low-predation (LP) and high-predation
      (HP) habitats in four Trinidadian streams. Guts were populated by several
      recurring, core bacteria that are related to other fish associates and rarely
      detected in the environment. Although gut communities of lab-reared guppies
      differed from those in the wild, microbiome divergence between ecotypes from the
      same stream was evident under identical rearing conditions, suggesting host
      genetic divergence can affect associations with gut bacteria. In the field, gut
      communities varied over time, across streams and between ecotypes in a stream
      specific manner. This latter finding, along with PICRUSt predictions of
      metagenome function, argues against strong parallelism of the gut microbiome in
      association with LP ecotype evolution. Thus, bacteria cannot be invoked in
      facilitating the heightened reliance of LP guppies on lower-quality diets. We
      argue that the macroevolutionary microbiome convergence seen across animals with
      similar diets may be a signature of secondary microbial shifts arising some time
      after host-driven adaptation. 

PMID- 25575312
TI  - Culture and molecular-based profiles show shifts in bacterial communities of the
      upper respiratory tract that occur with age.
AB  - The upper respiratory tract (URT) is a crucial site for host defense, as it is
      home to bacterial communities that both modulate host immune defense and serve as
      a reservoir of potential pathogens. Young children are at high risk of
      respiratory illness, yet the composition of their URT microbiota is not well
      understood. Microbial profiling of the respiratory tract has traditionally
      focused on culturing common respiratory pathogens, whereas recent culture
      independent microbiome profiling can only report the relative abundance of
      bacterial populations. In the current study, we used both molecular profiling of
      the bacterial 16S rRNA gene and laboratory culture to examine the bacterial
      diversity from the oropharynx and nasopharynx of 51 healthy children with a
      median age of 1.1 years (range 1-4.5 years) along with 19 accompanying parents.
      The resulting profiles suggest that in young children the nasopharyngeal
      microbiota, much like the gastrointestinal tract microbiome, changes from an
      immature state, where it is colonized by a few dominant taxa, to a more diverse
      state as it matures to resemble the adult microbiota. Importantly, this
      difference in bacterial diversity between adults and children accompanies a
      change in bacterial load of three orders of magnitude. This indicates that the
      bacterial communities in the nasopharynx of young children have a fundamentally
      different structure from those in adults and suggests that maturation of this
      community occurs sometime during the first few years of life, a period that
      includes ages at which children are at the highest risk for respiratory disease. 

PMID- 25575314
TI  - Studies on antitumor mechanism of two planar platinum(II) complexes with 8
      hydroxyquinoline: synthesis, characterization, cytotoxicity, cell cycle and
      apoptosis.
AB  - [Pt(Q)2] (1) and [Pt(MQ)2] (2) exhibited enhanced cytotoxicity against BEL-7404,
      Hep-G2, NCI-H460, T-24, A549 tumor cells but low cytotoxicity on normal HL-7702
      cells. 1 and 2 could cause the cell cycle arrest in G2 and S phase, respectively.
      While pifithrin-alpha, a specific p53 inhibitor, induced cell cycle arrest in G1
      phase. Although 1, 2 and pifithrin-alpha caused serious inhibition on p53, 1 and
      2 significantly cause the loss of mitochondrial membrane potential and increase
      of the reactive oxygen species level, cytochrome c, apaf-1 and caspase-3/9 ratio
      in BEL-7404 cells. 1 and 2 may trigger the cell apoptosis through a mitochondrial
      dysfunction pathway whereas pifithrin-alpha does not. The interactions of 1 and 2
      with DNA are most probably via an intercalation. 

PMID- 25575316
TI  - Introduction: special issue on old lesbians: exploring community, relationships,
      friendship, and well being.
AB  - This introduction begins with memories of homophobia the editors experienced to
      remind the reader of the general climate old lesbians faced in their younger
      years. Rationale for studying old lesbians and the relevance of the articles
      contained in this issue are described. Some different ways old lesbians identify
      that may affect policy decision and research analysis are included. Early
      significant research on the topic of old lesbians is noted and suggestions for
      future research studies are recommended. 

PMID- 25575313
TI  - Syntheses, characterization, interaction with DNA, cytotoxic and apoptosis of two
      novel complexes of Zn(II) and Mn(II) with 2-methyl-1H-4,5-imidazoledicarboxylic
      acid.
AB  - Two new complexes, Zn(L)2(H2O)2 (1) and Mn(L)2(H2O)2 (2) [L = 2-Methyl-1H-4,5
      imidazoledicarboxylic acid] were synthesized and characterized by elemental
      analysis, infrared spectroscopy, and single crystal X-ray diffraction.
      Intramolecular weak interactions, such as hydrogen-bond and intermolecular
      interactions were presented in the complexes. The activities of the complexes
      binding with DNA, and cytotoxic activities were studied. The binding of complexes
      with fish sperm DNA (FS-DNA) was investigated by fluorescence spectra. Gel
      electrophoresis assay demonstrated the ability of the complexes to cleave the
      pBR322 plasmid DNA. The cytotoxic activities of the complexes were tested against
      the KB cell line. Cytotoxic activity studies showed the two complexes exhibited
      significant cancer cell inhibitory rate. The most active compound was complex 1
      with IC50 and CC50value of 36.5, 429, with the selectivity index (SI = 11.75)
      among the tested compounds. 

PMID- 25575318
TI  - Ghosted images: old lesbians on screen.
AB  - Screen images of old lesbians combine modes of representing female gender,
      lesbian sexuality, and old age, all of which contain layers of otherness within a
      hetero-patriarchal and youth-centered society. Analyzing a range of films, from
      independent to mainstream cinema, this article explores how the ghosted lesbian
      paradigm intersects with narratives of aging as decline in representations of
      lesbian characters who are over the age of sixty. The spectral matters of
      illness, death, mourning, and widowhood inevitably culminate in an unhappy
      ending. Removed from a lesbian community context, intergenerational continuity
      vanishes and the old lesbian emerges as the cultural other. 

PMID- 25575317
TI  - Ageism in the lesbian community.
AB  - Ageist messages are everywhere. Lesbians of all ages must raise their awareness
      of the harm done by ageism and actively combat it. 

PMID- 25575319
TI  - Silence, death, and D/discourse: critical literary practices with lesbian
      seniors.
AB  - This article reports on a federally funded research project in which old lesbians
      were invited to separate out and examine the complicated strands of lives lived
      through times of great social change-times in which notions of "woman,"
      "sexuality," and "subjectivity" have been both over- and under-determined by
      dominant discourse (Stein, 1997). We argue, with Haug (1992), that close
      attention to the personal is central to critical feminist perspectives and that
      writers can become more aware of normalizing cultural influences when they pay
      close attention to language. In this article, we support our position with a case
      study of one participant in our "language school" (Haug, 1992). As we analyzed
      her written life narratives and oral testimony, we conclude that she was able to
      reconsider comfortable "coming out" narratives in order to construct new meaning
      and to challenge her understandings of the past. 

PMID- 25575320
TI  - Old lesbians in the UK: community and friendship.
AB  - Drawing on data from the first large-scale comprehensive study of older lesbian
      life in the United Kingdom, this article explores the nature of friendship and
      community among old lesbians. Strong friendship bonds and social networking
      emerge as key features of old lesbian culture. In particular the article focuses
      on "chosen families," including relationships with ex-lovers, and on the
      extensive network of both organized and informal social groups that continue to
      structure and support a sense of community among old lesbians. It shows the
      lasting importance of friendships and social structures formed earlier in life
      against a background of stigmatization, homophobia, and heterosexism, and argues
      for the recognition of these communities of identity by those who care for older
      people. 

PMID- 25575321
TI  - Lift every voice: voices of African-American lesbian elders.
AB  - Old lesbians of African descent have experienced racism, heterosexism,
      homophobia, and ageism. This article explores the topics of aging, ageism,
      heterosexism, and minority stress among older African-American lesbians. The
      narratives and subsequent analysis offer significant contributions to the
      dialogue regarding Black aging lesbians in the aging and lesbian, gay, bisexual,
      and transgender (LGBT) communities generally and in the African-American and
      African-American lesbian communities specifically. 

PMID- 25575322
TI  - Waking up: LGBT in old age from a provider's front lines perspective.
AB  - A startling and deeply unsettling question from a nursing home resident leads to
      self-reflection, questions about the fate of LGBT residents in nursing homes and
      other aging facilities, and a program to address their needs and educate service
      providers. 

PMID- 25575323
TI  - Older lesbians and work in the Australian health and aged care sector.
AB  - While research has identified challenges lesbians face in the workplace, there is
      limited understanding of the particular experiences of older lesbians, especially
      those working in the health and aged care sector. This article draws on the
      stories of four women who participated in a narrative research project on lesbian
      and gay people's experiences of health and aged care. It highlights the need for
      future research to examine the complexity of identity expression and community
      affiliation, how people negotiate "coming out" in the workplace, the impact of
      discrimination, and the resources (such as friends) available to lesbians in the
      workplace. 

PMID- 25575324
TI  - Elder transgender lesbians: exploring the intersection of age, lesbian sexual
      identity, and transgender identity.
AB  - This study is the first to examine the experiences and needs of an international
      sample of current, English-speaking, lesbian, transgender-identified (trans
      lesbian) adults around a number of later life and end-of-life perceptions,
      preparations, and concerns. I analyzed a subset (n = 276) of the cross-sectional
      data collected from the online Trans MetLife Survey on Later-Life Preparedness
      and Perceptions in Transgender-Identified Individuals (N = 1,963). I assessed
      perceptions and fears around aging, preparation for later life, and end-of-life
      as well as numerous demographic and psycho-social variables. Despite the overall
      feeling that they have aged successfully, the respondent trans-lesbian population
      harbors significant fears about later life. I found that this population, while
      better-prepared than the overall respondent trans-identified population, is still
      ill-prepared for the major legalities and events that occur in the later to end
      of-life time periods. 

PMID- 25575325
TI  - Loneliness and belongingness in older lesbians: the role of social groups as
      "community".
AB  - This article explores loneliness and isolation in older lesbians, looking at the
      benefits offered by an over-55 fortnightly social group in Yorkshire. I argue
      that the women interviewed were more vulnerable to loneliness than their
      heterosexual counterparts as a direct consequence of many years of privacy and
      self-concealment and because they were more likely to be single, childless, and
      have fractured relationships with birth families; all significant losses viewed
      by the women as the "price you paid" for being a lesbian. Although the group did
      not completely alleviate loneliness, it provided a place of safety and offered a
      sanctuary where participants could be themselves and where friendships and other
      groups were formed. For many women, the group's exclusivity to older lesbians and
      bisexual women was deeply significant and influenced their decision to attend. I
      suggest that such groups have a vital role to play in promoting older lesbian,
      gay, bisexual, and transgender well-being and offering protection against
      loneliness and isolation in older age. 

PMID- 25575326
TI  - "Pink" life stories in Amsterdam.

PMID- 25575327
TI  - Share the Care for the LGBT Community.

PMID- 25575328
TI  - Who gets to tell history?

PMID- 25575329
TI  - Notes on art & aging.

PMID- 25575330
TI  - Urgent: the Lesbian Home Movie Project.

PMID- 25575331
TI  - Lesbian blood drives as community-building activism in the 1980s.
AB  - As gay men began voluntarily withdrawing from blood donation in the early 1980s,
      lesbians in community with gay men in several U.S. cities organized drives to
      replenish the blood supply. These drives were sometimes the continuation of
      previously established drives by gay-lesbian organizations or faith communities,
      sometimes new initiatives in response to HIV/AIDS. However, after the initial
      publicity, mention of lesbian blood drives in print is both scarce and brief.
      Focusing on drives organized from 1983 to 1992 by a group known as San Diego
      Blood Sisters, this article is an initial step in documenting lesbian blood
      drives to inform and enrich conversations about histories of responses to
      HIV/AIDS, theoretical discussions of how community connections in the lesbian,
      gay, bisexual, transgender, and queer spectrum are enacted and understood, and
      emerging research on intersections of gender and sexuality as they are expressed
      through blood donorship. 

PMID- 25575332
TI  - Claiming lesbian history: the romance between fact and fiction.
AB  - The contested field of lesbian history exists along a continuum, with undisputed
      evidence on one end and informed speculation on the other. Lesbian historical
      fiction extends the spectrum, envisioning the lives of lesbian pirates, war
      heroes, pioneers, bandits, and stock romantic characters, as well as the handful
      of protagonists examined here whose quests specifically highlight the difficulty
      and importance of researching the lesbian past. The genre blossomed in the 1980s,
      just as the Foucauldian insistence that homosexual identity did not exist before
      the late nineteenth century gained sway in the academy. The proliferation of
      lesbian historical fictions signals the growing desire for more thorough (if not
      completely factual) historical underpinnings of the burgeoning lesbian
      identities, communities, and politics set in motion in the 1970s. 

PMID- 25575334
TI  - Evidence that brief self-affirming implementation intentions can reduce work
      related anxiety in downsize survivors.
AB  - BACKGROUND AND OBJECTIVES: Workers were recruited from a UK further education
      college during a period of organizational downsizing. This study assessed the
      effects of a brief health psychology intervention on work-related stress in
      downsize survivors. DESIGN AND METHODS: Sixty-six employees were randomly
      allocated to one of two conditions: one in which they were asked to create a work
      related self-affirming implementation intention (WS-AII) or a control. Feelings
      of anxiety and depression were measured before and after the intervention or
      control task and three weeks later. Job satisfaction, self-efficacy, and self
      esteem were also measured. RESULTS: There were statistically significant
      differences between the WS-AII condition and the control. Workers who created WS
      AIIs reported an immediate reduction in anxiety. This reduction was also observed
      in their appraisal of job-related anxiety three weeks later. There were no
      significant effects of WS-AIIs on depression, job satisfaction, or self-esteem.
      There was, however, a significant effect on self-efficacy with workers in the WS
      AII condition reporting greater self-efficacy. CONCLUSIONS: The present findings
      suggest that the integration of brief health psychology interventions, such as
      the WS-AII, into existing organizational practice may be of benefit to the well
      being of employees.

PMID- 25575335
TI  - Risk/Benefit Communication about Food-A Systematic Review of the Literature.
AB  - A systematic review relevant to the following research questions was conducted
      (1) the extent to which different theoretical frameworks have been applied to
      food risk/benefit communication and (2) the impact such food risk/benefit
      communication interventions have had on related risk/benefit attitudes and
      behaviors. Fifty four papers were identified. The analysis revealed that
      (primarily European or US) research interest has been relatively recent. Certain
      food issues were of greater interest to researchers than others, perhaps
      reflecting the occurrence of a crisis, or policy concern. Three broad themes
      relevant to the development of best practice in risk (benefit) communication were
      identified: the characteristics of the target population; the contents of the
      information; and the characteristics of the information sources. Within these
      themes, independent and dependent variables differed considerably. Overall, acute
      risk (benefit) communication will require advances in communication process
      whereas chronic communication needs to identify audience requirements. Both
      citizen's risk/benefit perceptions and (if relevant) related behaviors need to be
      taken into account, and recommendations for behavioral change need to be concrete
      and actionable. The application of theoretical frameworks to the study of risk
      (benefit) communication was infrequent, and developing predictive models of
      effective risk (benefit) communication may be contingent on improved theoretical
      perspectives. 

PMID- 25575336
TI  - Nasopharyngeal Carcinoma Invading the Orbit in a Young African American Male.

PMID- 25575337
TI  - Left or right? Rapid visuomotor coding of hand laterality during motor decisions.

PMID- 25575338
TI  - Direct cross-coupling of benzyl alcohols to construct diarylmethanes via
      palladium catalysis.
AB  - A direct arylation to furnish diarylmethanes from benzyl alcohols was realized
      through Pd(PPh3)4-catalyzed Suzuki-Miyaura coupling via benzylic C-O activation
      in the absence of any additives. The arylation is compatible with various
      functional groups. This development provides an atom- and step-economic way to
      approach a diarylmethane scaffold under mild and environmentally benign
      conditions. 

PMID- 25575339
TI  - Surgical Orthodontic Treatment for Open Bite in Noonan Syndrome Patient: A Case
      Report.
AB  - Noonan syndrome, characterized by short stature, facial anomalies, and congenital
      heart defects, may also be associated with hematopoietic disorders. Craniofacial
      anomalies in affected patients include hypertelorism and severe open bite
      associated with masticatory dysfunction. We treated a Noonan syndrome patient
      with a skeletal open bite. Surgical orthodontic treatment including two-jaw
      surgery established a good occlusal relationship after correction of severe
      anemia. Both upper and lower incisors were moved to upright positions, while
      clockwise rotation of the palatal plane and decreased mandibular plane angle were
      accomplished. Lower masticatory activity may affect posttreatment occlusion in
      such cases.

PMID- 25575340
TI  - Indacaterol, a once-daily beta2-agonist, versus twice-daily beta2-agonists or
      placebo for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Indacaterol is an inhaled long-acting beta2-agonist that is
      administered once daily and has been investigated as a treatment for chronic
      obstructive pulmonary disease (COPD). Four different doses have been investigated
      (75 mcg, 150 mcg, 300 mcg and 600 mcg). The relative effects of different doses
      of once-daily indacaterol in the management of patients with COPD are uncertain.
      OBJECTIVES: To compare the efficacy and safety of indacaterol versus placebo and
      alternative twice-daily long-acting beta2-agonists for the treatment of patients
      with stable COPD. SEARCH METHODS: We identified trials from the Cochrane Airways
      Group Specialised Register of trials (CAGR), handsearched respiratory journals
      and meeting abstracts and searched the Novartis trials registry and
      ClinicalTrials.gov. The date of the most recent search was 8 November 2014.
      SELECTION CRITERIA: We included all randomised controlled trials comparing
      indacaterol at any dose versus placebo or alternative long-acting beta2-agonists.
      Trials were required to be of at least 12 weeks' duration and had to include
      adults older than 18 years with a confirmed spirometric diagnosis of COPD. DATA
      COLLECTION AND ANALYSIS: Two review authors (JBG, EJD) independently assessed for
      possible inclusion all citations identified as a result of the search.
      Disagreements were resolved through discussion or, if required, through
      resolution by a third review author (RWB). One review author (JBG) extracted data
      from trials identified by the search and entered these data into Review Manager
      5.1 for statistical analysis. Data entry was cross-checked by a second review
      author (EJD, CJC). MAIN RESULTS: A total of 13 trials with 9961 participants were
      included in the review. Ten trials with a total of 8562 participants involved an
      indacaterol versus placebo comparison. Five trials with a total of 4133
      participants involved an indacaterol versus twice-daily beta2-agonist comparison.
      The comparator beta2-agonists were salmeterol, formoterol and eformoterol. One of
      these trials, with a total of 90 participants, provided no data that could be
      used in this review. Two trials included both indacaterol versus placebo and
      indacaterol versus twice-daily beta2-agonist comparisons. Trials were between 12
      weeks and 52 weeks in duration. Overall the quality of the evidence was strong,
      and risk of significant bias was minimal in most of the included studies.
      Enrolled participants had stable COPD across a range of spirometric severities.
      Forced expiratory volume in 1 second (FEV1) was generally between 30% and 80%
      predicted, and a mean FEV1 of approximately 50% was predicted in most studies.
      Patients with concurrent respiratory disease, including asthma, were excluded.
      Concomitant use of inhaled corticosteroids was permitted.The primary objectives
      were to compare trough FEV1 at the end of dosing, exacerbation rates and quality
      of life. Significant adverse events, mortality and dyspnoea were included as
      secondary outcomes. Compared with placebo, a significant and clinically relevant
      improvement in trough FEV1 was noted with indacaterol (mean difference (MD)
      149.11, 95% confidence interval (CI) 137.09 to 161.12). In addition, compared
      with placebo, a significant improvement in mean St George Respiratory
      Questionaire (SGRQ) score (MD -3.60, 95% CI -4.36 to -2.83) was reported, and the
      proportion of participants experiencing clinically relevant improvement in SGRQ
      score was significantly greater (odds ratio (OR) 1.63, 95% CI 1.46 to 1.84).
      Compared with twice-daily beta2-agonists, a small but statistically significant
      increase in trough FEV1 was seen with indacaterol (MD 61.71 mL, 95% CI 41.24 to
      82.17). Differences between indacaterol and twice-daily beta2-agonists in mean
      SGRQ scores (MD -0.81, 95% CI -2.28 to 0.66) and in the proportions of
      participants achieving clinically relevant improvements in SGRQ scores (OR 1.07,
      95% CI 0.87 to 1.32) were not statistically significant, but the confidence
      intervals are too wide to permit the conclusion that the treatments were
      equivalent. Data were insufficient for analysis of differences in exacerbation
      rates for both placebo and twice-daily beta2-agonist comparisons. AUTHORS'
      CONCLUSIONS: For patients with stable COPD, use of indacaterol versus placebo
      results in statistically significant and clinically meaningful improvements in
      lung function and quality of life. The clinical benefit for lung function is at
      least as good as that seen with twice-daily long-acting beta2-agonists. The
      comparative effect on quality of life remains uncertain, as important differences
      cannot be excluded.

PMID- 25575342
TI  - Flow-mediated synthesis of Boc, Fmoc, and Ddiv monoprotected diamines.
AB  - A series of monoprotected aliphatic diamines (21 examples) were synthesized via
      continuous flow methods. The carbamates and enamines were obtained in 45-91%
      yields using a 0.5 mm diameter PTFE tubular flow reactor. Using readily
      accessible protecting group precursors, the procedure serves as an attractive
      alternative to existing batch-mode synthetic routes by providing direct,
      multigram access to N-Boc-, N-Fmoc-, and N-Ddiv-protected compounds with
      productivity indexes of 1.2-3.6 g/h. 

PMID- 25575341
TI  - Assessing the scale of tumor heterogeneity by complete hierarchical segmentation
      of MRI.
AB  - In many cancers, intratumoral heterogeneity has been found in histology, genetic
      variation and vascular structure. We developed an algorithm to interrogate
      different scales of heterogeneity using clinical imaging. We hypothesize that
      heterogeneity of perfusion at coarse scale may correlate with treatment
      resistance and propensity for disease recurrence. The algorithm recursively
      segments the tumor image into increasingly smaller regions. Each dividing line is
      chosen so as to maximize signal intensity difference between the two regions.
      This process continues until the tumor has been divided into single voxels,
      resulting in segments at multiple scales. For each scale, heterogeneity is
      measured by comparing each segmented region to the adjacent region and
      calculating the difference in signal intensity histograms. Using digital phantom
      images, we showed that the algorithm is robust to image artifacts and various
      tumor shapes. We then measured the primary tumor scales of contrast enhancement
      heterogeneity in MRI of 18 rhabdomyosarcoma patients. Using Cox proportional
      hazards regression, we explored the influence of heterogeneity parameters on
      relapse-free survival. Coarser scale of maximum signal intensity heterogeneity
      was prognostic of shorter survival (p = 0.05). By contrast, two fractal
      parameters and three Haralick texture features were not prognostic. In summary,
      our algorithm produces a biologically motivated segmentation of tumor regions and
      reports the amount of heterogeneity at various distance scales. If validated on a
      larger dataset, this prognostic imaging biomarker could be useful to identify
      patients at higher risk for recurrence and candidates for alternative treatment. 

PMID- 25575344
TI  - The heterogeneity of concentrated prescribing behavior: Theory and evidence from
      antipsychotics.
AB  - We present two new findings based on annual antipsychotic US prescribing data
      from IMS Health on 2867 psychiatrists who wrote 50 or more prescriptions in 2007.
      First, many of these psychiatrists have prescription patterns that are
      statistically significantly different than random draws from national market
      shares for prescriptions by psychiatrists. For example, many have prescription
      patterns that are significantly more concentrated than such draws. Second, among
      psychiatrists who are the most concentrated, different prescribers often
      concentrate on distinct drugs. Motivated by these two findings, we then construct
      a model of physician learning-by-doing that fits these facts and generates two
      further predictions: both concentration (on one or a few drugs) and deviation
      (from the prescription patterns of others) should be smaller for high-volume
      physicians. We find empirical support for these predictions. Furthermore, our
      model outperforms an alternative theory concerning detailing by pharmaceutical
      representatives. 

PMID- 25575345
TI  - Near-field microscopy with a scanning nitrogen-vacancy color center in a diamond
      nanocrystal: A brief review.
AB  - We review our recent developments of near-field scanning optical microscopy
      (NSOM) that uses an active tip made of a single fluorescent nanodiamond (ND)
      grafted onto the apex of a substrate fiber tip. The ND hosting a limited number
      of nitrogen-vacancy (NV) color centers, such a tip is a scanning quantum source
      of light. The method for preparing the ND-based tips and their basic properties
      are summarized. Then we discuss theoretically the concept of spatial resolution
      that is achievable in this special NSOM configuration and find it to be only
      limited by the scan height over the imaged system, in contrast with the standard
      aperture-tip NSOM whose resolution depends critically on both the scan height and
      aperture diameter. Finally, we describe a scheme we have introduced recently for
      high-resolution imaging of nanoplasmonic structures with ND-based tips that is
      capable of approaching the ultimate resolution anticipated by theory. 

PMID- 25575343
TI  - Potential use of Pseudomonas koreensis AGB-1 in association with Miscanthus
      sinensis to remediate heavy metal(loid)-contaminated mining site soil.
AB  - Endophytic bacteria have the potential to promote plant growth and heavy
      metal(loid) (HM) removal from contaminated soil. Pseudomonas koreensis AGB-1,
      isolated from roots of Miscanthus sinensis growing in mine-tailing soil,
      exhibited high tolerance to HMs and plant growth promoting traits. Transmission
      electron microscope (TEM) analysis revealed that AGB-1 sequestered HMs
      extracellularly and their accumulation was visible as dark metal complexes on
      bacterial surfaces and outside of the cells. DNA sequencing of HM resistance
      marker genes indicated high homology to the appropriate regions of the arsB,
      ACR3(1), aoxB, and bmtA determinants. Inoculating mining site soil with AGB-1
      increased M. sinensis biomass by 54%, chlorophyll by 27%, and protein content by
      28%. High superoxide dismutase and catalase activities, and the lower
      malondialdehyde content of plants growing in AGB-1-inoculated soil indicate
      reduced oxidative stress. Metal(loid) concentrations in roots and shoots of
      plants grown in inoculated soil were higher than those of the controls in pot
      trials with mine tailing soil. Results suggest that AGB-1 can be used in
      association with M. sinensis to promote phytostabilization and remediation of HM
      contaminated sites.

PMID- 25575346
TI  - On-chip detection of non-classical light by scalable integration of single-photon
      detectors.
AB  - Photonic-integrated circuits have emerged as a scalable platform for complex
      quantum systems. A central goal is to integrate single-photon detectors to reduce
      optical losses, latency and wiring complexity associated with off-chip detectors.
      Superconducting nanowire single-photon detectors (SNSPDs) are particularly
      attractive because of high detection efficiency, sub-50-ps jitter and nanosecond
      scale reset time. However, while single detectors have been incorporated into
      individual waveguides, the system detection efficiency of multiple SNSPDs in one
      photonic circuit-required for scalable quantum photonic circuits-has been limited
      to <0.2%. Here we introduce a micrometer-scale flip-chip process that enables
      scalable integration of SNSPDs on a range of photonic circuits. Ten low-jitter
      detectors are integrated on one circuit with 100% device yield. With an average
      system detection efficiency beyond 10%, and estimated on-chip detection
      efficiency of 14-52% for four detectors operated simultaneously, we demonstrate,
      to the best of our knowledge, the first on-chip photon correlation measurements
      of non-classical light. 

PMID- 25575347
TI  - Immobilization of DNA aptamers via plasma polymerized allylamine film to
      construct an endothelial progenitor cell-capture surface.
AB  - The endothelial progenitor cells (EPCs) capture stent has drawn increasing
      attentions and become one of the most promising concepts for the next generation
      vascular stent. In this regard, it is of great significance to immobilize a
      molecule with the ability to bind EPC for rapid in vivo endothelialization with
      high specificity. In this work, a facile two-step method aimed at constructing a
      coating with specific EPC capturing aptamers is reported. The processes involves
      as the first-step deposition of plasma polymerized allylamine (PPAam) on a
      substrate to introduce amine groups, followed by the electrostatic adsorption of
      a 34 bases single strand DNA sequence to the PPAam surface as a second step
      (PPAam-DNA). Grazing incidence attenuated total reflection Fourier transform
      infrared spectroscopy (GATR-FTIR) and X-ray photoelectron spectroscopy (XPS)
      confirmed the successful immobilization of the aptamers. Quartz crystal
      microbalance with dissipation (QCM-D) real time monitoring result shows that
      about 175 ng/cm(2) aptamers were conjugated onto the PPAam surface. The
      interactions between the modified surfaces and human umbilical vein endothelial
      cells (ECs), smooth muscle cells (SMCs), and murine induced EPCs derived from
      mesenchymal stem cells (MSCs) were also investigated. It was demonstrated that
      PPAam-DNA samples could capture more EPCs, and present a cellular friendly
      surface for the proliferation of both EPCs and ECs but no effect on the
      hyperplasia of SMCs. Also, the co-culture results of 3 types of cells confirmed
      that the aptamer could specifically bond EPCs rather than ECs and SMCs,
      suggesting the competitive adhesion advantage of EPCs to ECs and SMCs. These data
      demonstrate that the EPC aptamer has large potential for designing an EPC
      captured stent and other vascular grafts with targeted in situ
      endothelialization.

PMID- 25575348
TI  - Effect of surface chemistry on the integrin induced pathway in regulating
      vascular endothelial cells migration.
AB  - The migration of vascular endothelial cells (ECs) is essential for
      reendothelialization after implantation of cardiovascular biomaterials.
      Reendothelialization is largely determined by surface properties of implants. In
      this study, surfaces modified with various chemical functional groups (CH3, NH2,
      COOH, OH) prepared by self-assembled monolayers (SAMs) were used as model system.
      Expressions and distributions of critical proteins in the integrin-induced
      signaling pathway were examined to explore the mechanisms of surface chemistry
      regulating EC migration. The results showed that SAMs modulated cell migration
      were in the order CH3>NH2>OH>COOH, determined by differences in the expressions
      of focal adhesion components and Rho GTPases. Multiple integrin subunits showed
      difference in a surface chemistry-dependent manner, which induced a stepwise
      activation of signaling cascades associated with EC migration. This work provides
      a broad overview of surface chemistry regulated endothelial cell migration and
      establishes association among the surface chemistry, cell migration behavior and
      associated integrin signaling events. Understanding the relationship between
      these factors will help us to understand the surface/interface behavior between
      biomaterials and cells, reveal molecular mechanism of cells sensing surface
      characterization, and guide surface modification of cardiovascular implanted
      materials. 

PMID- 25575349
TI  - Polyvinylidene fluoride/silane-treated hydroxyapatite mixed matrix membrane for
      enzyme capturing.
AB  - The silane coupling agent, N-(beta-aminoethyl)-gamma-aminopropyltrimethoxy silane
      (KH792), was employed to modify the surfaces of nano-hydroxyapatite (HAP)
      particles. The mixed matrix membranes (MMMs) were prepared by embedding pure HAP
      and HAP modified with KH792 (KH792-HAP) inside polyvinylidene fluoride (PVDF)
      matrix respectively. The MMMs were further characterized concerning permeability
      and adsorption capacity. Langmuir adsorption isotherm provides better fit for HAP
      and KH792-HAP than Freundlich isotherm. KH792-HAP has better distribution in the
      polymeric matrix compared to HAP in the polymeric matrix. The MMMs showed
      purification of enzyme via static adsorption and dynamic adsorption, and showed
      the potential of using MMMs for enzyme capturing in enzyme purification
      techniques. The lysozyme (LZ) was used as a model enzyme. The properties and
      structures of MMMs prepared by immersion phase separation process were
      characterized by pure water flux, LZ adsorption and scanning electron microscopy
      (SEM). 

PMID- 25575350
TI  - Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4
      exocytosis through cortical actin remodeling.
AB  - Akt2 and its downstream effectors mediate insulin-stimulated GLUT4-storage
      vesicle (GSV) translocation and fusion with the plasma membrane (PM). Using mass
      spectrometry, we identify actin-capping protein Tropomodulin 3 (Tmod3) as an Akt2
      interacting partner in 3T3-L1 adipocytes. We demonstrate that Tmod3 is
      phosphorylated at Ser71 on insulin-stimulated Akt2 activation, and Ser71
      phosphorylation is required for insulin-stimulated GLUT4 PM insertion and glucose
      uptake. Phosphorylated Tmod3 regulates insulin-induced actin remodelling, an
      essential step for GSV fusion with the PM. Furthermore, the interaction of Tmod3
      with its cognate tropomyosin partner, Tm5NM1 is necessary for GSV exocytosis and
      glucose uptake. Together these results establish Tmod3 as a novel Akt2 effector
      that mediates insulin-induced cortical actin remodelling and subsequent GLUT4
      membrane insertion. Our findings suggest that defects in cytoskeletal remodelling
      may contribute to impaired GLUT4 exocytosis and glucose uptake.

PMID- 25575352
TI  - Sponging up metals: bacteria associated with the marine sponge Spongia
      officinalis.
AB  - The present study explored the bacteria of the sponge Spongia officinalis in a
      metal-polluted environment, using PCR-DGGE fingerprinting, culture-dependent
      approaches and in situ hybridization. The sponge samples collected over three
      consecutive years in the Western Mediterranean Sea contained high concentrations
      of zinc, nickel, lead and copper determined by ICP-MS. DGGE signatures indicated
      a sponge specific bacterial association and suggested spatial and temporal
      variations. The bacterial culturable fraction associated with S. officinalis and
      tolerant to heavy metals was isolated using metal-enriched microbiological media.
      The obtained 63 aerobic strains were phylogenetically affiliated to the phyla
      Proteobacteria, Actinobacteria, and Firmicutes. All isolates showed high
      tolerances to the selected heavy metals. The predominant genus Pseudovibrio was
      localized via CARD-FISH in the sponge surface tissue and validated as a sponge
      associated epibiont. This study is the first step in understanding the potential
      involvement of the associated bacteria in sponge's tolerance to heavy metals. 

PMID- 25575353
TI  - Endoscopic ultrasound-directed transgastric ERCP (EDGE) for Roux-en-Y anatomy: a
      novel technique.
AB  - BACKGROUND: Patients with Roux-en-Y gastric bypass (RYGB) anatomy pose challenges
      when endoscopic retrograde cholangiopancreatography (ERCP) is required. Deep
      enteroscopy-assisted ERCP can allow pancreaticobiliary intervention in these
      patients, but with limited success. This case series describes endoscopic
      ultrasound-directed transgastric ERCP (EDGE) for patients following RYGB.
      METHODS: Patients with RYGB anatomy undergoing EDGE at a tertiary care center
      were included in this prospective single-arm feasibility study. All procedures
      were performed in two stages. First a 16-Fr percutaneous endoscopic gastrostomy
      (PEG) was placed in the excluded stomach using endoscopic ultrasound (EUS)
      guidance. Second, ERCP was performed through the newly fashioned gastrostomy and
      a transcutaneous fully covered metal esophageal stent. RESULTS: Six patients (5
      women, 1 man) with RYGB anatomy underwent EDGE. EUS-guided PEG placement was
      successful in all six patients (100 %). Antegrade ERCP was successful in all six
      patients (100 %) with the stages being separated by a mean of 5.8 days. The mean
      procedure times for the two stages were 81 minutes and 98 minutes. Two patients
      (33 %) had localized PEG site infections that were managed with oral antibiotics.
      There were no adverse events related to ERCP. CONCLUSIONS: EDGE is both feasible
      and safe to perform in RYGB patients. Given the high success rates of our recent
      experience, we suspect that this technique can be performed as a one-stage
      procedure to provide a cost-effective, minimally invasive option for a common
      problem in a growing patient population.

PMID- 25575354
TI  - Comparison of the different responses of surface plasmon resonance and quartz
      crystal microbalance techniques at solid-liquid interfaces under various
      experimental conditions.
AB  - A molecular level understanding of the phenomena taking place at solid-liquid
      interfaces, ranging from changes in mass to conformation changes, is the key to
      developing and improving many chemical and biological systems and their
      scientific and medical applications. Surface plasmon resonance (SPR) and quartz
      crystal microbalance (QCM) techniques are often coupled to achieve this
      understanding. We divided various experimentally relevant scenarios into the
      following six categories: boundary solutions; surface modifications;
      conformation; viscoelastic properties; molecular ruler; and mass sensitivity. For
      each case, based on theoretical analyses, we discuss the following four points
      with respect to discrete adsorbates at solid-liquid interfaces: (1) the different
      types of information that can be obtained, why it can be obtained and how to
      obtain it; (2) the origins of many current approaches and why they are imperfect;
      (3) guidelines for experimental design; and (4) possible studies, such as the
      effect of dimensional confinement and adsorption forces on the ability of
      conformational changes to occur on the receipt of external stimuli and the
      hysteresis in these changes. 

PMID- 25575355
TI  - Lesion Sites Associated with Allocentric and Egocentric Visuospatial Neglect in
      Acute Stroke.
AB  - Visuospatial neglect is a disorder that can often result from stroke and is
      characterized by an inability to attend to contralesional stimuli. Two common
      subtypes include allocentric (object-centered) neglect and egocentric (viewer
      centered) neglect. In allocentric neglect, spatial inattention is localized to
      the contralesional side of an object regardless of its relative position to the
      observer. In egocentric neglect, spatial inattention is localized to the
      contralesional side of the individual's midline. The neuroanatomical correlates
      of each subtype are unknown. However, recent work has suggested that damage to
      temporal, inferior parietal, and occipital areas may result in allocentric
      neglect and that damage to frontoparietal areas may result in egocentric neglect.
      We used voxel-based lesion-symptom mapping (VLSM) to compare lesion location to
      behavioral performance on the conventional six subtests of the Behavioral
      Inattention Test (BIT) in 62 subjects with acute right hemisphere ischemic
      stroke. Results identified an anatomical dissociation in lesion location between
      subjects with neglect based on poor performance on allocentric tests (line
      bisection, copying, and drawing tasks) and on egocentric tests (star, letter, and
      line cancellation). VLSM analyses revealed that poor performance on the
      allocentric tests was associated with lesions to the superior and inferior
      parietal cortices, and the superior and middle temporal gyri. In contrast, poor
      performance on the egocentric tests was associated with lesions in the precentral
      gyrus, middle frontal gyrus, insula, and putamen. Interestingly, the letter
      cancellation test and average performance on egocentric tests were associated
      with frontal and parietal lesions. Some of these parietal lesion locations
      overlapped with lesion locations associated with allocentric neglect. These
      findings are consistent with suggestions that damage to temporal and parietal
      areas is more associated with allocentric neglect and damage to frontal lobe
      areas is more associated with egocentric neglect. 

PMID- 25575356
TI  - Melorheostosis: segmental osteopoikilosis or a separate entity?
AB  - PURPOSE: Melorheostosis is a progressive hyperostotic bone disease that commonly
      affects the appendicular skeleton. Melorheostosis has a significant degree of
      overlap with other hyperostosis conditions including osteopoikilosis and likely
      represent varying degrees of a clinical spectrum. METHODS: This is a report of 2
      patients with melorheostosis who presented with different clinical presentations
      and involvement of different anatomic locations. RESULTS: One of the patients
      presented with foot size asymmetry along with intermittent foot pain and limping.
      This patient also had irregular nonblanching yellow plaque-like lesion on the
      forehead. The second patient presented with abnormal gait but no pain.
      Radiographs demonstrated endosteal hyperostosis, which were consistent with a
      mixed picture of melorheostosis and osteopoikilois. Genetic testing of the LEMD3
      gene from a blood sample was negative in both cases. CONCLUSIONS: The diagnosis
      of melorheostosis can be made based on the clinical and radiographic features and
      can be challenging to differentiate from other hyperostosis conditions. LEVEL OF
      EVIDENCE: Level V.

PMID- 25575357
TI  - Short-term and Long-term Clinical Results of the Surgical Correction of Thumb-in
      Palm Deformity in Patients With Cerebral Palsy.
AB  - BACKGROUND: Thumb-in-palm deformity disturbs a functional grip of the hand in
      patients with cerebral palsy. Reported recurrence rates after surgical correction
      are contradicting and earlier studies are limited to short-term follow-up.
      Therefore, the aim of this retrospective clinical outcome study is to evaluate
      the success rate of surgical correction of thumb-in-palm deformity around 1 year
      and at a minimum of 5 years follow-up. In addition, long-term patient
      satisfaction of the treatment is evaluated. METHODS: Patients with cerebral palsy
      who underwent a surgical correction for their thumb-in-palm deformity between
      April 2003 and April 2008 at the Academic Medical Center in Amsterdam were
      included. All patients were classified into 4 categories according to the
      assessment system of the Committee on Spastic Hand Evaluation. The result of
      surgery was considered "short-term successful" and "long-term successful" when,
      respectively, short-term and long-term classification was better compared with
      preoperative. The association between the patient satisfaction outcomes and the
      long-term clinical outcomes were statistically analyzed. RESULTS: Data were
      collected from 39 patients and their charts. The success rate was 87% at short
      term follow-up, which in the long term decreased to 80%. Interestingly, thumb
      position deteriorated in 29% of the patients between short-term and long-term
      follow-up. In the long term, 74% of the patients were satisfied with the position
      of their thumb and 87% would undergo the surgery again. Both these outcomes were
      statistically significant associated with the long-term success rate (P<0.05).
      CONCLUSIONS: The surgical correction of thumb-in-palm deformity has a high
      clinical success rate and patient satisfaction in the long term. However, it
      should be taken into account that the clinical result around 1 year postoperative
      cannot be considered final.

PMID- 25575358
TI  - Management of Thoracic Insufficiency Syndrome in Patients With Jeune Syndrome
      Using the 70 mm Radius Vertical Expandable Prosthetic Titanium Rib.
AB  - BACKGROUND: Jeune syndrome (JS) often results in lethal thoracic insufficiency
      syndrome. Since 1991, vertical expandable prosthetic titanium rib Dynamic
      PosteroLateral Expansion Thoracoplasty was used at our institution for treatment
      of JS. This study assesses the safety and efficacy of this procedure. METHODS:
      Twenty-four JS patients were treated, 2 lost to follow-up, 17 with a minimum of 2
      year follow-up retrospectively reviewed for clinical course: Assisted Ventilation
      Rate, respiratory rate, capillary blood gases, pulmonary function testings, and
      complications. Upright anteroposterior/lateral radiographs were measured for Cobb
      angle, kyphosis, lordosis, thoracic width, and thoracic/lumbar spinal height.
      Computed tomography scan lung volumes were obtained in 12 patients. RESULTS: Mean
      age at initial implant was 23 months (7 to 62 mo) with an average 8.4 years (2.3
      to 15.6 y) of follow-up. Average chest width increased from 121 to 168 mm at
      follow-up (P<0.001). Preoperatively, 7/17 (41%) patients had scoliosis. The
      remainder developed scoliosis during treatment, 8 requiring additional implants.
      Thoracic and lumbar spinal height was normal preoperatively and stayed normal
      during treatment. Thoracic kyphosis/lumbar lordosis was stable. Average computed
      tomography scan total lung volumes increased 484 to 740 mm3 (P<0.001), and
      Assisted Ventilation Rate status tended to improve (P=0.07). Average forced vital
      capacity was 34% predicted at first test and 27% predicted at last follow-up.
      Early demise after surgery was common with multisystem disease. Mean respiratory
      rate decreased from 35 to 24 bpm at last follow-up (P<0.05). Survival rate of the
      22 patients was 68%. Migration of the rib cradles/titanium slings occurred in 12
      patients, superficial infections in 5 patients, deep infections in 4 patients,
      and wound dehiscence in 5 patients. Infection rate was 4.6% per procedure.
      CONCLUSIONS: The survival rate in JS with surgery was nearly 70% (compared with
      70% to 80% mortality without treatment) with less ventilator dependence. Both C1
      stenosis and scoliosis are common in JS. Spinal height in JS is normal.
      Complications are frequent, but tolerable in view of the clinical gains and
      increase in survival.

PMID- 25575359
TI  - Predicting the Presence of Adjacent Infections in Septic Arthritis in Children.
AB  - BACKGROUND: The gold standard for treatment of septic arthritis is urgent
      surgical debridement. Preoperative magnetic resonance imaging (MRI) may identify
      osteomyelitis, subperiosteal abscesses, and intramuscular abscesses, which
      frequently occur with septic arthritis. If these adjacent infections are not
      recognized, initial treatment may be inadequate. The purpose of this study is to
      develop a prediction algorithm to distinguish septic arthritis with adjacent
      infections from isolated septic arthritis to determine which patients should
      undergo preoperative MRI. METHODS: An IRB-approved retrospective review of 87
      children treated for septic arthritis was performed. All patients underwent MRI.
      Sixteen variables (age, sex, temperature, WBC, CRP, ESR, ANC, hematocrit,
      platelet count, heart rate, systolic blood pressure, diastolic blood pressure,
      symptom duration, weight-bearing status, prior antibiotic therapy, and prior
      hospitalization) from admission were reviewed. Graphical and logistical
      regression analysis was used to determine variables independently predictive of
      adjacent infection. Optimal cutoff values were determined for each variable and a
      prediction algorithm was created. Finally, the model was applied to our patient
      database and each patient with isolated septic arthritis or adjacent infection
      was stratified based upon the number of positive predictive factors. RESULTS: A
      total of 36 (41%) patients had isolated septic arthritis and 51 (59%) had septic
      arthritis with adjacent foci. Five variables (age above 3.6 y, CRP>13.8 mg/L,
      duration of symptoms >3 d, platelets <314*10 cells/MUL, and ANC>8.6*10 cells/MUL)
      were found to be predictive of adjacent infection and were included in the
      algorithm. Patients with >=3 risk factors were classified as high risk for septic
      arthritis with adjacent infection (sensitivity: 90%, specificity: 67%, positive
      predictive value: 80%, negative predictive value: 83%). CONCLUSIONS: Age, CRP,
      duration of symptoms, platelet count, and ANC were predictive of adjacent
      infections. Patients who met >=3 criteria are at high risk for adjacent infection
      and may benefit from preoperative MRI. LEVEL OF EVIDENCE: Level III-retrospective
      comparative study.

PMID- 25575360
TI  - Septic Arthritis of the Elbow in Children: Clinical Presentation and
      Microbiological Profile.
AB  - BACKGROUND: Septic arthritis of the elbow in children is a rare but important
      musculoskeletal infection, and there is little published data to guide treating
      clinicians. The purpose of this study was to describe the clinical presentation
      and diagnostic findings, associated pathology, and microbiological profile of
      septic arthritis of the elbow in a pediatric population. METHODS: We
      retrospectively analyzed a consecutive series of children who had an elbow
      arthrocentesis for presumed septic arthritis and whose joint aspirates were
      positive for microbial growth. Data collected included demographics, presenting
      signs and symptoms, imaging, and laboratory data, including culture results.
      RESULTS: Twelve children underwent diagnostic arthrocentesis of the elbow joint
      for septic arthritis at an average age of 6 years and 9 months (range, 2 mo to 13
      y and 7 mo). Every child had pain, localized erythema and edema, and restricted
      range of motion; 10/12 were febrile. Mean duration of symptoms prior to joint tap
      was 4 days (range, 1 to 14 d). Concurrent osteomyelitis was found in 7 patients,
      as confirmed with magnetic resonance imaging (MRI): 5 at initial presentation and
      2 after readmission for persistent symptoms. Causative pathogens were MSSA (7),
      MRSA (2), Group G streptococcus (1), Pseuodomonas aureginosa (1), and
      Streptococcus pneumonia (1). ESR was >40 mm/h in 8/11 patients, CRP was >2 mg/dL
      in all patients, and synovial WBC count was >50,000 cells/mm in 8/9 patients. One
      patient developed fulminant sepsis during hospitalization and 2 children were
      readmitted within 30 days of discharge for unrecognized osteomyelitis and/or
      recurrence of septic arthritis of the elbow. CONCLUSION: In 12 children studied
      with septic arthritis, S. aureus was the most common pathogen. Diagnosis is often
      delayed, and in most cases inflammatory markers were elevated (ESR>40 mm/h, CRP>2
      mg/dL). Concomitant osteomyelitis is quite common, and therefore magnetic
      resonance imaging should be considered as part of the diagnostic work-up for this
      condition. LEVEL OF EVIDENCE: Level IV-Case series.

PMID- 25575361
TI  - Incidence of Deep Vein Thrombosis and Pulmonary Embolism in the Elective
      Pediatric Orthopaedic Patient.
AB  - BACKGROUND: Although venous thromboembolism (VTE) has been well studied in the
      pediatric trauma population, rates of VTE associated with elective pediatric
      orthopaedic procedures have not been addressed in current literature. The purpose
      of this retrospective study was to identify the incidence of VTE in the elective
      pediatric orthopaedic surgical population and delineate subsets of this
      population at greatest risk. This study may provide valuable data to begin the
      process of resolving the controversy surrounding deep vein thrombosis prophylaxis
      in the pediatric orthopaedic population. METHODS: The Pediatric Health
      Information System was queried for patients admitted on an ambulatory or
      inpatient basis, aged below 18 years, from January 2006 to March 2011 during
      which an elective orthopaedic surgery was the principal procedure performed.
      Patients with diagnoses or procedures related to infection, trauma, malignancy,
      or coagulopathies were excluded. Patients admitted through the emergency
      department or whose orthopaedic procedure was not performed on the admission date
      were excluded. Age, sex, ethnicity, race, admission year, and all
      procedures/diagnoses were recorded. The presence of VTE at the index admission or
      any subsequent readmission within 90 days was recorded. All criteria were coded
      using ICD-9-CM codes. Generalized logistic regression analyses were used to
      identify factors related to VTE. RESULTS: A total of 143,808 admissions (117,676
      patients) matched the inclusion criteria. Thirty-three had a VTE during the index
      admission with an additional 41 at subsequent readmissions, for a total incidence
      of 0.0515% by admission and 0.0629% by patient. In the multivariable model,
      variables significantly (P<0.05) related to VTE included increasing age,
      admission type, diagnosis of metabolic conditions, obesity, and/or syndromes, and
      complications of implanted devices and/or surgical procedures. No procedure
      variables were significantly related to VTE in the multivariable model.
      CONCLUSIONS: The incidence of VTE in this cohort of pediatric patients undergoing
      elective orthopaedic surgery was 0.0515%. In children, underlying diagnosis seems
      to be a stronger predictor of VTE than procedures performed. Diagnosis with a
      metabolic condition, syndrome, and/or obesity, complications of implanted devices
      and/or surgical procedures, older age, and admission as an inpatient were
      significantly related to the development of a VTE. LEVEL OF EVIDENCE: Level IV
      case series.

PMID- 25575362
TI  - A New Classification System to Report Complications in Growing Spine Surgery: A
      Multicenter Consensus Study.
AB  - INTRODUCTION: The use of growth-sparing instrumentation in pediatric spinal
      deformity is associated with a significant incidence of adverse events. However,
      there is no consistent way to report these complications, allowing for meaningful
      comparison of different growth-sparing techniques and strategies. The purpose of
      this study is to develop consensus for a new classification system to report
      these complications. METHODS: The authors, who represent lead surgeons from 5
      major pediatric spine centers, collaborated to develop a classification system to
      report complications associated with growing spine surgery. Following IRB
      approval, this system was then tested using a minimum of 10 patients from each
      center with at least 2-year follow-up after initial implantation of growing
      instrumentation to assess ease of use and consistency in reporting complications.
      Inclusion criteria were only patients who had surgical treatment of early onset
      scoliosis and did not include casting or bracing.Complications are defined as an
      unplanned medical event in the course of treatment that may or may not affect
      final outcome. Severity refers to the level of care and urgency required to treat
      the complication, and can be classified as device related or disease related.
      Severity grade (SV) I is a complication that does not require unplanned surgery,
      and can be corrected at the next scheduled surgery. SVII requires an unplanned
      surgery, with SVIIA requiring a single trip and SVIIB needing multiple trips for
      resolution. SVIII is a complication that substantially alters the planned course
      of treatment. Disease-related complications are classified as grade SVI if no
      hospitalization is required and grade SVII if hospitalization is required. SVIV
      was defined as death, either disease or device related. RESULTS: A total of 65
      patients from 5 institutions met enrollment criteria for the study; 56 patients
      had at least 1 complication and 9 had no complications. There were 14 growing
      rods, 47 VEPTRs, ,and 4 hybrid constructs. The average age at implant was 4.7
      years. There were an average of 5.4 expansions, 1.6 revisions, and 0.8 exchanges
      per patient. The minimum follow-up was 2 years. The most common complications
      were migration (60), infection (31), pneumonia (21), and instrumentation failure
      (23). When classified, the complications were grade I (57), grade IIA (79), grade
      IIB (10), and grade III (6). CONCLUSIONS: Well-documented uncertainty in clinical
      decision making in this area highlights the need for more rigorous clinical
      research. Reporting complications standardized for severity and impact on the
      course of treatment in growing spine surgery is a necessary prerequisite for
      meaningful comparative evaluation of different treatment options. This study
      shows that although complications were common, only 9% (SVIII) were severe enough
      to change the planned course of treatment. SIGNIFICANCE: We propose that future
      studies reporting complications of different methods of growth-sparing spine
      surgery use this classification moving forward so that meaningful comparisons can
      be made between different treatment techniques.

PMID- 25575363
TI  - Delay in diagnosis of chronic obstructive pulmonary disease: reasons and
      solutions.
AB  - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a crippling
      disease with a high worldwide prevalence. It is the fifth-leading cause of death
      worldwide and estimated to become the third-leading cause of death by 2030. This
      review highlights recent studies that discuss reasons for and possible solutions
      to the delay in diagnosis of COPD. RECENT FINDINGS: Delay in COPD diagnosis is
      multifactorial and can be grouped into healthcare provider-related factors,
      patient-related factors, and heterogeneity in the disease itself. The current
      literature strongly supports the lack of awareness and knowledge about COPD among
      healthcare providers as an important factor in misdiagnosis and/or delays in
      diagnosis. Ironically, COPD is both underdiagnosed and overdiagnosed. SUMMARY:
      Achieving the goal of early diagnosis in COPD needs a major overhaul and culture
      change in primary care settings. Respiratory symptoms in a smoker 40 years or
      above should trigger automatic health alert and spirometry indications. Awareness
      of tobacco-related injury is the first building block in prevention and cure.

PMID- 25575351
TI  - Comparison between an alternative and the classic definition of chronic
      bronchitis in COPDGene.
AB  - RATIONALE: Previous studies on chronic bronchitis (CB) have used varying
      definitions. OBJECTIVES: We sought to compare an alternative CB definition, using
      the St. George's Respiratory Questionnaire (SGRQ), a commonly used assessment
      tool, with the classic definition and to investigate if it had independent or
      additive value. METHODS: We analyzed data from 4,513 subjects from Global
      Initiative for Chronic Obstructive Lung Disease groups 1 to 4 in the COPDGene
      cohort. We compared the classic definition of CB with the SGRQ definition,
      defined by their answers to the questions about both cough and phlegm. We
      compared the Classic CB+ versus CB- groups, and the SGRQ CB+ and CB- groups. We
      also analyzed the cohort split into four groups: Classic CB+/SGRQ CB+, Classic
      CB+/SGRQ CB-, Classic CB-/SGRQ CB+, Classic CB-/SGRQ CB-. MEASUREMENTS AND MAIN
      RESULTS: A total of 26.1% subjects were Classic CB+, whereas 39.9% were SGRQ CB+.
      When the SGRQ definition was compared with the Classic CB definition, using this
      as the gold standard, the SGRQ CB definition had a sensitivity and specificity of
      0.87 and 0.77, respectively. The SGRQ CB+ and Classic CB+ groups were strikingly
      similar, with more respiratory symptoms and exacerbations, worse lung function,
      and greater airway wall thickness. In addition, the Classic CB+/SGRQ CB+, Classic
      CB+/SGRQ CB-, and Classic CB-/SGRQ CB+ groups shared similar characteristics as
      well. CONCLUSIONS: The SGRQ CB definition identifies more subjects with chronic
      cough and sputum who share a similar phenotype identified by the Classic CB
      definition. The addition of the SGRQ CB definition to the classic one can be used
      to identify more patients with chronic obstructive pulmonary disease at risk for
      poor outcomes.

PMID- 25575364
TI  - Global perspectives of emerging occupational and environmental lung diseases.
AB  - PURPOSE OF REVIEW: New technologies continue to be introduced into the workplace
      and the environment. These novel technologies also bring in new hazards leading
      to evolving patterns of established occupational and environmental diseases, as
      well as novel conditions never before encountered. RECENT FINDINGS: Many of these
      emerging conditions have appeared in media outlets or in the literature as case
      reports. These sentinel cases often serve as a warning sign for subsequent
      outbreaks. This review will discuss environmental and occupational lung diseases
      and exposures from a global perspective. These diseases and exposures include
      environmental exposure to asbestos and lung diseases, accelerated silicosis in
      sandblasting jean workers, coal worker's pneumoconiosis in surface coal miners,
      health effects of indoor air pollution from burning of biomass fuels and
      exposures to heavy metals and potential health effects from hydraulic fracturing
      (fracking). Other emerging conditions are also discussed, including smog in
      developing countries, sand storms in Asia and the Middle East and respiratory
      illnesses from nanoparticles and man-made fibres. SUMMARY: Clinicians must remain
      vigilant for potential occupational and environmental exposures, especially when
      evaluating patients with unusual and unique presentation, so that occupational
      and environmental risk factors may be identified, and monitoring and preventive
      measures can be implemented early.

PMID- 25575365
TI  - Severe acute exacerbations of chronic obstructive pulmonary disease: does the
      dosage of corticosteroids and type of antibiotic matter?
AB  - PURPOSE OF REVIEW: Severe acute exacerbations of chronic obstructive pulmonary
      disease (AECOPD) are significant events that result in substantial morbidity and
      mortality. Antibiotic therapy and systemic corticosteroids are important
      treatments for patients with severe AECOPD. The objective of this review is to
      summarize the most recent evidence concerning antibiotic and corticosteroid
      therapy, with a focused evaluation on the contribution of antibiotic type and
      corticosteroid dosage on patient outcomes. RECENT FINDINGS: Macrolides should be
      considered the antibiotic of choice for prevention of AECOPD in patients who
      qualify for therapy. Macrolides, fluoroquinolones, and beta-lactams are all
      reasonable treatment options for severe AECOPD and the decision to use one over
      the other should be based upon patient characteristics and institutional or
      regional antimicrobial susceptibility patterns. The best available evidence now
      suggests that higher-dose corticosteroids are not superior to treatment with
      lower-dose corticosteroids in patients with severe AECOPD. Additionally, longer
      durations of systemic corticosteroid therapy do not improve clinical outcomes.
      SUMMARY: Several antibiotic options are efficacious in the management of severe
      AECOPD and drug selection should be patient-specific. Recent studies suggest that
      lower dosages and shorter durations of corticosteroid treatment may be prudent.

PMID- 25575366
TI  - Emerging spectrum of deployment-related respiratory diseases.
AB  - PURPOSE OF REVIEW: Military personnel and civilian contractors who have deployed
      to Iraq, Afghanistan, and other south-west Asia locations since 2001 may be at
      risk for a spectrum of disorders collectively known as deployment-related
      respiratory diseases. Diagnosis is often challenging as typical symptoms of
      cough, dyspnea, and decreased exercise tolerance may be accompanied by subtle
      abnormalities on noninvasive diagnostic testing despite significant
      histopathologic abnormalities identified on lung biopsy. This review describes
      the emerging spectrum of deployment-related respiratory diseases, addresses
      diagnostic challenges, and updates recommendations for evaluation and management.
      RECENT FINDINGS: Investigators from Vanderbilt University, Nashville, TN, found
      constrictive bronchiolitis on 38 surgical lung biopsies in a case series of army
      deployers with unexplained chest symptoms. More recently, in a group of 50
      consecutive deployed patients evaluated at San Antonio Military Medical Center,
      36% were found to have airway hyperreactivity, whereas 42% were undiagnosed.
      SUMMARY: We propose a diagnostic and management algorithm for evaluation of the
      patient with postdeployment respiratory symptoms who are at risk of deployment
      related lung disease.

PMID- 25575368
TI  - Multidimensional approach to dyspnea.
AB  - PURPOSE OF REVIEW: This review focuses on sensory-perceptual and
      affective/emotional domains of dyspnea. RECENT FINDINGS: Recent studies have
      underscored the multidimensional aspect of dyspnea, which comprises three major
      dimensions: the sensory-perceptual domain, the affective distress, and the
      symptom impact or burden. Sensory-perceptual dimension includes ratings of
      dyspnea intensity and its quality, that is, 'how breathing feels like.' Affective
      distress addresses the question of 'how distressing breathing is' and focuses on
      the perception of immediate unpleasantness or the cognitive evaluative response
      about the potential consequence of what is perceived. Symptom impact evaluates
      how dyspnea impacts on functional ability/disability, health status, and/or
      quality of life. SUMMARY: Dyspnea is a debilitating symptom and the major reason
      for seeking medical attention in patients with cardiorespiratory diseases.
      Dyspnea predicts morbidity, quality of life, and mortality in several different
      conditions. Notwithstanding sometimes patients neglect to report dyspnea to their
      clinician because they feel it is not sufficiently relevant to be documented. The
      relationship between what the patients feel, how they express themselves about
      the disease, and how caregivers interpret their complaints is complex and not
      easy to decipher. It is important to correctly recognize dyspnea, and optimize
      and individualize its clinical management.

PMID- 25575369
TI  - Multi-stakeholder taskforces in Bangladesh--a distinctive approach to build
      sustainable tobacco control implementation.
AB  - The MPOWER policy package enables countries to implement effective, evidence
      based strategies to address the threat posed to their population by tobacco. All
      countries have challenges to overcome when implementing tobacco control policy.
      Some are generic such as tobacco industry efforts to undermine and circumvent
      legislation; others are specific to national or local context. Various factors
      influence how successfully challenges are addressed, including the legal
      political framework for enforcement, public and administrative attitudes towards
      the law, and whether policy implementation measures are undertaken. This paper
      examines District Tobacco Control Taskforces, a flexible policy mechanism
      developed in Bangladesh to support the implementation of the Smoking and Tobacco
      Products Usage (Control) Act 2005 and its 2013 Amendment. At the time of this
      study published research and/or data was not available and understanding about
      these structures, their role, contribution, limitations and potential, was
      limited. We consider Taskforce characteristics and suggest that the "package"
      comprises a distinctive tobacco control implementation model. Qualitative data is
      presented from interviews with key informants in ten districts with activated
      taskforces (n = 70) to provide insight from the perspectives of taskforce members
      and non-members. In all ten districts taskforces were seen as a crucial tool for
      tobacco control implementation. Where taskforces were perceived to be functioning
      well, current positive impacts were perceived, including reduced smoking in
      public places and tobacco advertising, and increased public awareness and
      political profile. In districts with less well established taskforces,
      interviewees believed in their taskforce's 'potential' to deliver similar
      benefits once their functioning was improved. Recommendations to improve
      functioning and enhance impact were made. The distinctive taskforce concept and
      lessons from their development may provide other countries with a flexible local
      implementation model for tobacco control. 

PMID- 25575367
TI  - The chronic bronchitis phenotype in chronic obstructive pulmonary disease:
      features and implications.
AB  - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a major public
      health problem that is projected to rank fifth worldwide in terms of disease
      burden and third in terms of mortality. Chronic bronchitis is associated with
      multiple clinical consequences, including hastening lung function decline,
      increasing risk of exacerbations, reducing health-related quality of life, and
      possibly raising all-cause mortality. Recent data suggest greater elucidation on
      the risk factors, radiologic characteristics, and treatment regimens. Our goal
      was to review the literature on chronic bronchitis that has been published in the
      past few years. RECENT FINDINGS: A growing body of literature that more carefully
      describes environmental risk factors, epidemiology, and genetics associated with
      chronic bronchitis. In addition, as computed tomography technology continues to
      improve, the radiologic phenotype associated with chronic bronchitis is better
      understood. SUMMARY: With these new data, the clinician can recognize the newly
      described risk factors and the associated phenotype for chronic bronchitis and
      entertain new treatment options for this high-risk population.

PMID- 25575371
TI  - Accumulation and maternal transfer of perfluorooctane sulphonic acid in yellow
      legged (Larus michahellis) and Audouin's gull (Larus audouinii) from the Ebro
      Delta Natural Park.
AB  - This study aimed to determine the accumulation and maternal transfer of
      perfluorooctane sulphonic acid (PFOS) in yellow-legged gulls (YLG, Larus
      michahellis) and the protected species Audouin's gull (AG, Larus audouinii),
      which cohabit in the Ebro Delta Natural Park (Catalonia, Spain). The Estimated
      Daily Intake (EDI) through diet (fish and crayfish), depuration rates and
      transfer capacity from blood to first eggs was studied for a set of 44 pairs. For
      AG, mean (+/-SD) EDI was of 128 +/- 36 ng/d in males and 119 +/- 32 ng/d in
      females, and for YLG, 170 +/- 48 ng/d in males and 159 +/- 42 ng/d in females.
      PFOS levels in blood were higher in males than females (60.6 +/- 21 and 61.1 +/-
      2 7ng/g ww in AG and YLG males versus 25.2 +/- 12 and 27.3 +/- 14 ng/g ww in AG
      and YLG females), with little differences among species. The lower levels in
      females were attributed to the annual release of PFOS to eggs during the laying
      period, which was estimated of 5544 +/- 1571 ng/egg for AG females and 6716 +/-
      2689 ng/egg for YLG. The overall mass balance of PFOS calculated for both species
      clearly demonstrates that uptake is higher than elimination rates, considering
      depuration rates and transfer of PFOS to eggs, and this explains that PFOS is
      accumulated in gulls in a yearly basis.

PMID- 25575370
TI  - Association between self-reported global sleep status and prevalence of
      hypertension in Chinese adults: data from the Kailuan community.
AB  - BACKGROUND: Assessment of sleep only by sleep duration is not sufficient. This
      cross-sectional study aimed to investigate the potential association of self
      reported global sleep status, which contained both qualitative and quantitative
      aspects, with hypertension prevalence in Chinese adults. METHODS: A total of 5461
      subjects (4076 of them were male) were enrolled in the current study and were
      divided into two groups with the age of 45 years as the cut-off value. Sleep
      status of all subjects was assessed using the standard Pittsburgh Sleep Quality
      Index (PSQI). Hypertension was defined as blood pressure >=140/90 mmHg in the
      current study. RESULTS: After adjusting for basic cardiovascular characteristics,
      the results of multivariate logistic regression indicated that sleep status,
      which was defined as the additive measurement of sleep duration and sleep
      quality, was associated with hypertension prevalence in males of both age groups
      (odds ratio (OR) = 1.11, 95% confidence interval (CI), 1.07-1.15, p < 0.05; OR =
      1.12, 95% CI, 1.08-1.15, p < 0.05) and in females aged <=45years (OR = 1.10, 95%
      CI, 1.02-1.18, p < 0.05). As one component of PSQI, short sleep duration was
      associated with hypertension prevalence only in Chinese male subjects, but this
      association disappeared after the further adjustment of the other components of
      PSQI that measured the qualitative aspect of sleep. CONCLUSION: Association
      between sleep status and hypertension prevalence in Chinese adults varied by age
      and sex. Sleep should be measured qualitatively and quantitatively when
      investigating its association with hypertension.

PMID- 25575372
TI  - The critical fetal stage for maternal manganese exposure.
AB  - Prenatal exposure and the health effects of that exposure have been intensively
      studied for a variety of environmental pollutants and trace elements. However,
      few studies have compared susceptibilities among the three trimesters of
      gestation. Manganese (Mn) is a naturally occurring and abundant trace element in
      the environment. Although the effects of Mn on animals are well documented,
      knowledge of the effects of Mn exposure on pregnant women and fetuses remains
      limited. A longitudinal study was conducted by collecting blood samples during
      all three trimesters, and Mn exposure was completely characterized during
      gestation. The aims of this study were to examine the effects of maternal Mn
      exposure on neonatal birth outcomes and to explore the critical stage of these
      effects. In total, 38, 76 and 76 samples were obtained from singleton pregnant
      women in their first, second and third trimesters, respectively. The cohort of
      pregnant women was selected at a medical center in northern Taiwan. Erythrocyte
      samples were collected during the first, second and third trimesters of
      gestation. Erythrocyte Mn concentrations were measured by inductively coupled
      plasma mass spectrometry. Neonatal birth outcomes were evaluated immediately
      after delivery. A multivariate regression model was used to determine the
      associations between maternal Mn levels in erythrocytes in each trimester and
      neonatal birth outcomes. The geometric mean concentrations of Mn were 2.93
      MUg/dL, 3.96 MUg/dL and 4.41 MUg/dL in the first, second and third trimesters,
      respectively. After adjusting for potential confounders, a consistently negative
      association was found between maternal Mn levels throughout the three trimesters
      and birth outcomes. Log-transformed Mn levels in maternal erythrocytes in the
      second trimester were significantly associated with neonatal birth weight, head
      and chest circumferences, respectively (beta=-556.98 g, p=0.038; beta=-1.87 cm,
      p=0.045; beta=-2.74 cm, p=0.024). Despite the limited sample size in the first
      trimester, negative effects of maternal Mn levels on birth weight (beta=-1108.95
      g, p<0.01) and chest circumference (beta=-4.40 cm, p=0.019) were also observed.

PMID- 25575373
TI  - Hearing preservation among patients undergoing cochlear implantation.
AB  - INTRODUCTION: Despite successful preservation of low-frequency hearing in
      patients undergoing cochlear implantation (CI) with shorter electrode lengths,
      there is still controversy regarding which electrodes maximize hearing
      preservation (HP). The thin straight electrode array (TSEA) has been suggested as
      a full cochlear coverage option for HP. However, very little is known regarding
      its HP potential. METHODS: A retrospective review was performed at two tertiary
      academic medical centers, reviewing the electronic records for 52 patients (mean,
      58.2 yr; range, 11-85 yr) implanted with the Cochlear Nucleus CI422 Slim Straight
      (Centennial, CO, USA) electrode array, referred to herein as the thin straight
      electrode array or TSEA. All patients had a preoperative low-frequency pure-tone
      average (LFPTA) of 85 dB HL or less. Hearing thresholds were measured at initial
      activation (t1) and 6 months after activation (t2). HP was assessed by evaluating
      functional HP using a cutoff level of 85 dB HL PTA. RESULTS: At t1, 54% of the
      subjects had functional hearing; 33% of these subjects had an LFPTA between 71
      and 85 dB HL, and 17% had an LFPTA between 56 and 70 dB HL. At t2, 47% of the
      patients had functional hearing, with 31% having an LFPTA between 71 and 85 dB
      HL. DISCUSSION: Preliminary research suggests that the TSEA has the potential to
      preserve functional hearing in 54% of patients at t1. However, 22% (n = 6) of the
      patients who had functional hearing at t1 (n = 28) lost their hearing between t1
      and t2. Further studies are needed to evaluate factors that influence HP with the
      TSEA electrode and determine the speech perception benefits using electric and
      acoustic hearing over electric alone.

PMID- 25575374
TI  - Scalar localization by cone-beam computed tomography of cochlear implant
      carriers: a comparative study between straight and periomodiolar precurved
      electrode arrays.
AB  - OBJECTIVE: To compare the incidence of dislocation of precurved versus straight
      flexible cochlear implant electrode arrays using cone-beam computed tomography
      (CBCT) image analyses. STUDY DESIGN: Consecutive nonrandomized case-comparison
      study. SETTINGS: Tertiary referral center. PATIENTS: Analyses of patients' CBCT
      images after cochlear implant surgery. INTERVENTION(S): Precurved and straight
      flexible electrode arrays from two different manufacturers were implanted. A
      round window insertion was performed in most cases. Two cases necessitated a
      cochleostomy. The patients' CBCT images were reconstructed in the coronal
      oblique, sagittal oblique, and axial oblique section. MAIN OUTCOME MEASURES: The
      insertion depth angle and the incidence of dislocation from the scala tympani to
      the scala vestibuli were determined. RESULTS: The CBCT images and the incidence
      of dislocation were analyzed in 54 patients (61 electrode arrays). Thirty-one
      patients were implanted with a precurved perimodiolar electrode array and 30
      patients with a straight flexible electrode array. A total of nine (15%) scalar
      dislocations were observed in both groups. Eight (26%) scalar dislocations were
      observed in the precurved array group and one (3%) in the straight array group.
      Dislocation occurred at an insertion depth angle between 170 and 190 degrees in
      the precurved array group and at approximately 370 degrees in the straight array
      group. CONCLUSION: With precurved arrays, dislocation usually occurs in the
      ascending part of the basal turn of the cochlea. With straight flexible electrode
      arrays, the incidence of dislocation was lower, and it seems that straight
      flexible arrays have a higher chance of a confined position within the scala
      tympani than perimodiolar precurved arrays.

PMID- 25575375
TI  - Outward versus inward head thrusts with video-head impulse testing in normal
      subjects: does it matter?
AB  - OBJECTIVE: To investigate the effect of outward and inward head thrusts on the
      efficacy of compensatory eye movements generated during the video-Head Impulse
      Test (v-HIT) in healthy subjects. INTERVENTION: Diagnostic. Rapid movements of
      the head were performed either from the midline towards the side (outward
      thrusts) or from the side towards the midline (inward thrusts). MAIN OUTCOME
      MEASURE: Gain of the vestibulo-ocular reflex (VOR) as reported by two different v
      HIT devices. RESULTS: A small but statistically significant increase of the VOR
      gain was found for outward impulses. This small difference is likely to be
      attributed to increased neck strain during outward impulses, and/or
      hypothetically, that an effect of Alexander's law during fast, high-frequency VOR
      could play a role. However, the differences are minute. CONCLUSION: We conclude
      that because the difference in the VOR gain between outward and inward thrusts
      was slight, both methods are acceptable for clinical use.

PMID- 25575376
TI  - Secondary ion mass spectrometry signatures for verifying declarations of fissile
      material production.
AB  - Direct analysis of uranium enrichment facility components were performed using
      secondary ion mass spectrometry (SIMS). A standard protocol was developed to
      enable preparation of SIMS samples from a corroded pipe piece without disturbing
      the corrosion layer. Unique uranium, oxygen and fluorine containing signatures
      were discovered in the corrosion layer by performing a mass scan of the region of
      interest from 230 to 280amu. These signatures identified the source of the
      corrosion layer as uranium hexafluoride (UF6) or an associated hydrolysis
      product. Isotopic analysis of the corrosion layer determined enrichment of (235)U
      to a value of 0.0116+/-0.0019 for the (235)U/(238)U isotopic ratio as compared to
      the NIST traceable standard (CRM 112-A) with a natural (235)U/(238)U isotopic
      ratio of 0.007254+/-0.000004. SIMS depth analysis revealed that the corrosion
      layer was isotopically homogenous to a depth of ~23.5um. Optical profilometry
      measurements prior to and following SIMS depth analysis were used to determine a
      sputter rate of 0.48nm/s for 18.5keV O(-) ion bombardment of the corrosion layer.
      The data presented is conclusive evidence that SIMS depth analysis can be used to
      identify novel nuclear archeology signatures from uranium enrichment components
      and perform meaningful isotopic analysis of these signatures. 

PMID- 25575377
TI  - Magnetic control of transverse electric polarization in BiFeO3.
AB  - Numerous attempts have been made to realize crossed coupling between
      ferroelectricity and magnetism in multiferroic materials at room temperature.
      BiFeO3 is the most extensively studied multiferroic material that shows
      multiferroicity at temperatures significantly above room temperature. Here we
      present high-field experiments on high-quality mono-domain BiFeO3 crystals reveal
      substantial electric polarization orthogonal to the widely recognized one along
      the trigonal c axis. This novel polarization appears to couple with the domains
      of the cycloidal spin order and, hence, can be controlled using magnetic fields.
      The transverse polarization shows the non-volatile memory effect at least up to
      300 K.

PMID- 25575378
TI  - Federal Public Health Workforce Development: An Evidence-Based Approach for
      Defining Competencies.
AB  - OBJECTIVE: This study reports the use of exploratory factor analysis to describe
      essential skills and knowledge for an important segment of the domestic public
      health workforce-Centers for Disease Control and Prevention (CDC) project
      officers-using an evidence-based approach to competency development and
      validation. DESIGN: A multicomponent survey was conducted. Exploratory factor
      analysis was used to examine the underlying domains and relationships between
      competency domains and key behaviors. The Cronbach alpha coefficient determined
      the reliability of the overall scale and identified factors. SETTING AND
      PARTICIPANTS: All domestic (US state, tribe, local, and territorial) grantees who
      received funding from the CDC during fiscal year 2011 to implement nonresearch
      prevention or intervention programs were invited to participate in a Web-based
      questionnaire. MAIN OUTCOME MEASURE(S): A total of 34 key behaviors representing
      knowledge, skills, and abilities, grouped in 7 domains-communication, grant
      administration and management, public health applied science and knowledge,
      program planning and development, program management, program monitoring and
      improvement, and organizational consultation-were examined. RESULTS: There were
      795 responses (58% response rate). A total of 6 factors were identified with
      loadings of 0.40 or more for all 34 behavioral items. The Cronbach alpha
      coefficient was 0.95 overall and ranged between 0.73 and 0.91 for the factors.
      CONCLUSIONS: This study provides empirical evidence for the construct validity of
      6 competencies and 34 key behaviors important for CDC project officers and serves
      as an important first step to evidence-driven workforce development efforts in
      public health.

PMID- 25575379
TI  - Four shades of brown: tuning of electrochromic polymer blends toward high
      contrast eyewear.
AB  - We report a straightforward strategy of accessing a wide variety of colors
      through simple predictive color mixing of electrochromic polymers (ECPs). We have
      created a set of brown ECP blends that can be incorporated as the active material
      in user-controlled electrochromic eyewear. Color mixing of ECPs proceeds in a
      subtractive fashion, and we acquire various hues of brown through the mixing of
      cyan and yellow primaries in combination with orange and periwinkle-blue
      secondary colors. Upon oxidation, all of the created blends exhibit a change in
      transmittance from ca. 10 to 70% in a few seconds. We demonstrate the
      attractiveness of these ECP blends as active materials in electrochromic eyewear
      by assembling user-controlled, high-contrast, fast-switching, and fully solution
      processable electrochromic lenses with colorless transmissive states and colored
      states that correspond to commercially available sunglasses. The lenses were
      fabricated using a combination of inkjet printing and blade-coating to illustrate
      the feasibility of using soluble ECPs for high-throughput and large-scale
      processing. 

PMID- 25575380
TI  - Hydrogel patterning by diffusion through the matrix and subsequent light
      triggered chemical immobilization.
AB  - A novel approach to hyaluronic acid (HA) hydrogel with a chemical gradient of the
      matrix-linked bisphosphonate (BP) groups is presented. The method consists of two
      steps, including initial generation of physical gradient patterns of BPs by
      diffusion of BP acrylamide reagent into HA matrix carrying thiol groups and
      subsequent chemical immobilization of the BP groups by UV light-triggered thiol
      ene addition reaction. This gradient hydrogel permits spatial three-dimensional
      regulation of secondary interactions of different molecules with the polymer
      matrix. In particular, graded amounts of cytochrome c (cyt c) were reversibly
      absorbed in the hydrogel, thus enabling the subsequent spatially controlled
      release of the therapeutic protein. The obtained patterned hydrogel acts also as
      a unique reactor in which peroxidase-catalyzed oxidation of a substrate is
      determined by spatial position of the enzyme (cyt c) in the matrix resulting in a
      range of product concentrations. As an example, matrix template-assisted
      oxidation of 3,3',5,5'-tetarmethylbenzydine (TMB) in the presence of H2O2 occurs
      simultaneously at different rates within the gradient hydrogel. Moreover, calcium
      binding to the gradient HABP hydrogel reflects the pattern of immobilized BP
      groups eventually leading to the graded biomineralization of the matrix. This
      approach opens new possibilities for use of hydrogels as dynamic models for
      biologic three-dimensional structures such as extracellular matrix. 

PMID- 25575381
TI  - Dynamics of Gastrovascular Circulation in the Hydrozoan Podocoryne carnea: the
      One-Polyp Case.
AB  - Time-lapse video microscopy and image analysis algorithms were used to generate
      high-resolution time series of the length and volume of a single hydrozoan polyp
      before and after feeding. A polyp of Podocoryne carnea prior to feeding is
      effectively static in length and volume. At 20{deg}C, feeding elicits 8
      millihertz (mHz) oscillations in polyp length and volume. A polyp connected to a
      colony by a single stolon displayed an abrupt transition from low-amplitude, 8
      mHz oscillations to large-amplitude, 6-mHz oscillations at 1.5-2 h after feeding.
      The transition was preceded by a substantial decrease in polyp volume and
      increase in length which coincided with the export of food items from the
      digestive cavity of the polyp into the colonial gastrovascular system. In
      contrast, 8-mHz oscillations of a polyp isolated from a colony continued for 12.7
      h after feeding, at which time particulates from the digestive cavity were
      exported into the hydrorhiza and a 4-mHz subharmonic became briefly dominant.
      Regular oscillatory behavior was terminated by regurgitation at comparable
      intervals post-feeding in coupled and isolated polyps. These observations are
      compatible with the hypothesis that the presence of nutrients in the digestive
      cavity induces polyp oscillations and that release of nutrients into the
      gastrovascular system similarly induces unfed polyps to oscillate, thereby
      distributing the contents of the fed polyp throughout the colony. 

PMID- 25575382
TI  - High contents of trimethylamine oxide correlating with depth in deep-sea teleost
      fishes, skates, and decapod crustaceans.
AB  - In muscles of shallow-living marine animals, the osmolyte trimethylamine N-oxide
      (TMAO) is reportedly found (in millimoles of TMAO per kilogram of tissue wet
      weight) at 30-90 in shrimp, 5-50 in crabs, 61-181 in skates, and 10-70 in most
      teleost fish. Recently our laboratory reported higher levels (83-211 mmol/kg),
      correlating with habitat depth, in deep-sea gadiform teleosts. We now report the
      same trend in muscles of other animals, collected off the coast of Oregon from
      bathyal (1800-2000 m) and abyssal plain (2850 m) sites. TMAO contents (mmol/kg +/
      SD) were as follows: zoarcid teleosts, 103 +/- 9 (bathyal) and 197 +/- 2
      (abyssal); scorpaenid teleosts, 32 +/- 0 (shallow) and 141 +/- 16 (bathyal);
      rajid skates, 215 +/- 13 (bathyal) and 244 +/- 23 (abyssal); caridean shrimp, 76
      +/- 16 (shallow), 203 +/- 35 (bathyal), and 299 +/- 28 (abyssal); Chionoecetes
      crabs, 22 +/- 2 (shallow) and 164 +/- 15 (bathyal). Deep squid, clams, and
      anemones also had higher contents than shallow species. Osmoconformers showed
      compensation between TMAO and other osmolytes. Urea contents (typically 300
      mmol/kg in shallow elasmobranchs) in skates were 214 +/- 5 (bathyal) and 136 +/-
      9 (abyssal). Glycine contents in shrimp were 188 +/- 17 (shallow) and 52 +/- 20
      (abyssal). High TMAO contents may reflect diet, reduce osmoregulatory costs,
      increase buoyancy, or counteract destabilization of proteins by pressure. 

PMID- 25575383
TI  - Differences in the Composition of Adhesive and Non-Adhesive Mucus From the Limpet
      Lottia limatula.
AB  - The mucus used by the limpet Lottia limatula to form glue-like attachments was
      compared biochemically to the slippery mucus produced during other activities,
      such as suction adhesion. Colorimetric assays revealed the protein content of the
      adhesive mucus to be 2.1 times greater than that of the non-adhesive form, and
      the carbohydrate content to be 1.9 times greater. Both forms of mucus contained
      roughly six times as much protein as carbohydrate, and there was no difference in
      their inorganic elemental compositions. Quantitative analysis of the protein
      content by SDS-PAGE and a scanning densitometer revealed a similar protein
      composition in both forms of mucus; but three notable differences emerged. First,
      the overall difference in protein concentration was confirmed. In addition, there
      was a 118 kD protein that was common only in the adhesive mucus, and a 68 kD
      protein that occurred only in the non-adhesive mucus. 

PMID- 25575384
TI  - Calcium Dependence of Settlement and Nematocyst Discharge in Actinulae of the
      Hydroid Tubularia mesembryanthemum.
AB  - The influence of Ca2+ and Mg2+ ions on both atrichous isorhiza (AI) discharge and
      settlement of actinular larvae of the hydroid Tubularia mesembryanthemum was
      investigated. Mg2+-supplemented artificial seawater (ASW) completely inhibited
      both events at a concentration of 206 mM, whereas lowered Mg2+ concentrations
      enhanced them. Ca2+ ions in the bathing solution highly regulated AI discharge
      and settlement, and Mg2+ ions may down-regulate these events. The effect of
      inorganic Ca2+-channel blockers, including Gd3+ and La3+, was also examined.
      Larval settlement was inhibited by Co2+, Ni2+, Cd2+, La3+, and Gd3+, with half
      inhibitory concentrations (IC50) of 5800, 260, 53, 45, and 7 {mu}M, respectively;
      AI discharge was also inhibited by these ions, with IC50 values of 6600, 500, 78,
      41, and 5 {mu}M, respectively. These results suggest possible involvement of
      stretch-activated Ca2+ channels in the signal transmission of both AI discharge
      and larval settlement. 

PMID- 25575385
TI  - Free radicals and chemiluminescence as products of the spontaneous oxidation of
      sulfide in seawater, and their biological implications.
AB  - The discovery of symbioses between marine invertebrates and sulfide-oxidizing
      bacteria at deep-sea hydrothermal vents and in other high-sulfide marine
      environments has stimulated research into the adaptations of metazoans to
      potentially toxic concentrations of sulfide. Most of these studies have focused
      on a particular action of sulfide--its disruption of aerobic metabolism by the
      inhibition of mitochondrial respiration--and on the adaptations of sulfide
      tolerant animals to avoid this toxic effect (1). We propose that sulfidic
      environments impose another, hitherto over-looked type of toxicity: exposure to
      free radicals of oxygen, which may be produced during the spontaneous oxidation
      of sulfide, thus imposing an oxidative stress. Here we present evidence that
      oxygen- and sulfur-centered free radicals are produced during the oxidation of
      sulfide in seawater, and we propose a reaction pathway for sulfide oxidation that
      is consistent with our observations. We also show that chemiluminescence at
      visible wavelengths occurs during sulfide oxidation, providing a possible
      mechanism for the unexplained light emission from hydrothermal vents (2, 3). 

PMID- 25575386
TI  - Metamorphosis in the Marine Snail Ilyanassa obsoleta, Yes or NO?
AB  - Metamorphosis is a crucial life-history event that can change an organism's form,
      function, behavior, and ecological interactions. In the Mollusca, several
      neurotransmitters and neuromodulators play inductive or inhibitory roles in the
      pathways that govern larval metamorphosis. Nitric oxide (NO) has been implicated
      in developmental processes in vertebrates and arthropods, but not previously in
      molluscs. We determined that NO donors block pharmacologically induced
      metamorphosis in the mud snail Ilyanassa obsoleta, whereas injections of
      inhibitors of nitric oxide synthase (NOS) allow competent larvae to become
      juveniles. We describe a new developmental role for NO, as an endogenous
      inhibitor of molluscan metamorphosis. 

PMID- 25575387
TI  - Development basis of phenotypic variation in egg production in a colonial
      ascidian: primary oocyte production versus oocyte development.
AB  - Colonies of the ascidian Botryllus schlosseri (a cyclical hermaphrodite) exhibit
      extreme variability in egg production, and there is a large genetic component to
      this phenotypic variation. Therefore, the developmental bases of variation among
      different genotypes was investigated. Colonies differing in egg production
      (assayed as number of eggs per asexual bud) were cultured in a common garden
      experiment, and buds were collected and fixed early in the reproductive cycle.
      The buds were serially sectioned, and the number and size of the oocytes in the
      developing ovaries were determined for the different genotypes. Because the buds
      were collected prior to the onset of vitellogenesis, they contained oocytes at
      the three previtellogenic stages. In reproductive colonies (>0.7 eggs per bud),
      there were negative relationships between the final number of eggs per bud and
      (1) the total number of oocytes present, (2) the number of stage 1 oocytes
      present, and (3) the number of stage 2 oocytes present. There was no relationship
      between these parameters in nonreproductive colonies (<0.3 eggs per bud). In
      contrast, the number of stage 3 oocytes per bud was positively correlated with
      the final number of eggs per bud in both reproductive and nonreproductive
      colonies. In reproductive animals there was a negative relationship between the
      total number of oocytes per bud and the percentage of oocytes at stage 3 in
      oogenesis. A principal component analysis revealed that a single vector equally
      weighted for the number of eggs per bud, the total number of oocytes per bud, and
      the percentage of oocytes at stage 3 accounted for 84% of the observed variation
      in reproductive colonies. These data indicate that the phenotypic variation in
      egg production among the B. schlosseri colonies in the Damariscotta River, Maine,
      is controlled by genetic variation in both the number of oocytes that populate
      developing ovaries, and the percentage of oocytes that reach stage 3 in
      oogenesis. 

PMID- 25575388
TI  - Late Larval Development and Onset of Symbiosis in the Scleractinian Coral Fungia
      scutaria.
AB  - Many corals that harbor symbiotic algae (zooxanthellae) produce offspring that
      initially lack zooxanthellae. This study examined late larval development and the
      acquisition of zooxanthellae in the scleractinian coral Fungia scutaria, which
      produces planula larvae that lack zooxanthellae. Larvae reared under laboratory
      conditions developed the ability to feed 3 days after fertilization; feeding
      behavior was stimulated by homogenized Artemia. Larvae began to settle and
      metamorphose 5 days after fertilization. In laboratory experiments, larvae
      acquired experimentally added zooxanthellae by ingesting them while feeding.
      Zooxanthellae entered the gastric cavity and were phagocytosed by endodermal
      cells. As early as 1 h after feeding, zooxanthellae were observed in both
      endodermal and ectodermal cells. Larvae were able to form an association with
      three genetically distinct strains of zooxanthellae. Both zooxanthellate and
      azooxanthellate larvae underwent metamorphosis, and azooxanthellate polyps were
      able to acquire zooxanthellae from the environment. Preliminary evidence suggests
      that the onset of symbiosis may influence larval development; in one study
      symbiotic larvae settled earlier than aposymbiotic larvae. Protein profiles of
      eggs and larvae throughout development revealed a putative yolk protein doublet
      that was abundant in eggs and 1-day-old larvae and was absent by day 6. This
      study is the first to examine the onset of symbiosis between a motile cnidarian
      host and its algal symbiont. 

PMID- 25575389
TI  - Ultraviolet Radiation and Distribution of the Solitary Ascidian Corella inflata
      (Huntsman).
AB  - The solitary ascidian Corella inflata is a common fouling organism in many areas
      of Puget Sound and the San Juan Archipelago, Washington, USA. Despite its
      abundance, it is conspicuously absent from areas that receive direct sunlight.
      Previous work suggests that ascidians in unshaded habitats can be overgrown and
      killed by algal overgrowth. In this study, we tested the hypothesis that UV
      irradiation contributes to C. inflata distribution by killing individuals exposed
      to direct sunlight. To test this, we exposed C. inflata embryos, larvae,
      juveniles, and adults to UV irradiation and measured the responses. We also
      tested for UV-absorbing compounds in larvae, juveniles, and adults. In the
      laboratory, UV significantly damaged all life stages; the earliest stages were
      most vulnerable. A 3-week UV exposure significantly shortened adult life span.
      Juveniles suffered 100% mortality after only 3 days. Tadpole larvae decreased
      settlement and metamorphosis after 1 day of UV exposure, and embryos exhibited
      developmental abnormalities after only 30 minutes of exposure. None of the life
      history stages had apparent UV-absorbing compounds. Given the vulnerability of
      this species to UV, we suggest that its unique life-history traits (i.e., time of
      spawning, brooding behavior, length of larval life) help it persist in its
      preferred habitat and avoid dispersal into inappropriate, UV-exposed areas. 

PMID- 25575390
TI  - Time in residence affects escape and agonistic behavior in adult male american
      lobsters.
AB  - Acquisition and retention of a shelter by a lobster are two of the variables that
      play a role in lobster agonistic interactions. Since shelter procurement and
      retention are important for lobster survival, behaviors related to this activity
      frequently outrank other daily behaviors (e.g., searching for food). Here, we
      examine the effects of time in residence on the parameters of the escape response
      of the American lobster, Homarus americanus. Adult male intermolt lobsters (Stage
      C4) were placed in an experimental tank for three different time periods (one
      hour, 24 hours, and 48 hours). The probability of eliciting an escape response
      was inversely related to the time spent in the tank. Eighty percent of the
      animals in residence for 1 h tailflipped in response to a threat, whereas only
      14% of the animals in residence for 48 h tailflipped. There were also significant
      changes in some of the parameters of the escape response among animals in
      residence for 24 h compared to those in residence for 1 h. The number of
      tailflips and the distance traveled were reduced, although frequency, velocity,
      acceleration, force, and work factors were not significantly different.
      Furthermore, with increased time in residence, lobsters switched from an
      avoidance or escape-prone behavior to an aggressive-prone behavior. Most of the
      animals in residence for 48 h approached and attacked a threat-stimulus rather
      than fleeing from it. On an empirically defined "index of aggressiveness," in
      which various behaviors were numerically ranked from least aggressive (0) to most
      aggressive (6), animals residing in the tank for 1 h had an average index value
      of 0.1 compared to a value of 5.0 for animals in residence for 48 h. These
      findings are consonant with the suggestion that lobsters that have occupied a
      given space for an extended period of time take possession of the site and defend
      it instead of fleeing when threatened with a threat-inducing stimulus; it
      supports the idea that shelter retention increases aggressiveness and diminishes
      avoidance behaviors. 

PMID- 25575391
TI  - Tunic morphology and cellulosic components of pyrosomas, doliolids, and salps
      (thaliacea, urochordata).
AB  - The morphology and cellulosic composition of the tunic was studied in pelagic
      tunicates (3 pyrosomas, 2 doliolids, and 13 salps). The tunic is transparent and
      gelatinous, consisting of an electron-dense cuticular layer with a fibrous tunic
      matrix. The thickness and density of the cuticular layer and of the tunic matrix
      differ from species to species. In some salps, the cuticular layer has numerous
      minute protrusions that are structurally identical to those found in several
      ascidians. Free mesenchymal cells (tunic cells) are distributed in the tunic.
      Whereas the number of tunic cells in the pyrosomas is similar to that in
      ascidians, there are many fewer tunic cells in doliolids and salps. These
      differences may be caused by the different functions of the tunic in each group.
      The existence of cellulose in the tunic was confirmed using electron diffraction
      in all of the species studied thus far. Their diffractograms indicate that the
      cellulose microfibrils consist of nearly pure I{beta} of the allomorph. These
      results show that tunic morphology and cellulosic composition are similar in
      ascidians and thaliaceans (pyrosomas, doliolids, and salps). The tunic is
      considered to be a homologous tissue in these animals, and their most recent
      common ancestor would have possessed this tissue. 

PMID- 25575403
TI  - Could changes in adiponectin drive the effect of statins on the risk of new-onset
      diabetes? The case of pitavastatin.
AB  - Statins represent the elective lipid-lowering strategy in hyperlipidemic and high
      cardiovascular-risk patients. Despite excellent safety and tolerability,
      reversible muscle-related and dose-dependent adverse events may decrease a
      patient's compliance. Large meta-analyses, post-hoc and genetic studies showed
      that statins might increase the risk of new-onset diabetes (NOD), particularly in
      insulin-resistant, obese, old patients. Race, gender, concomitant medication,
      dose and treatment duration may also contribute to this effect. Based on this
      evidence, to warn against the possibility of statin-induced NOD or worsening
      glycemic control in patients with already established diabetes, FDA and EMA
      changed the labels of all the available statins in the USA and Europe. Recent
      meta-analyses and retrospective studies demonstrated that statins'
      diabetogenicity is a dose-related class effect, but the mechanism(s) is not
      understood. Among statins, only pravastatin and pitavastatin do not deteriorate
      glycemic parameters in patients with and without type 2 diabetes mellitus.
      Interestingly, available data, obtained in small-scale, retrospective or single
      center clinical studies, document that pitavastatin, while ameliorating lipid
      profile, seems protective against NOD. Beyond differences in pharmacokinetics
      between pitavastatin and the other statins (higher oral bioavailability, lower
      hepatic uptake), its consistent increases in plasma adiponectin documented in
      clinical studies may be causally connected with its effect on glucose metabolism.
      Adiponectin is a protein with antiatherosclerotic, anti-inflammatory and
      antidiabetogenic properties exerted on liver, skeletal muscle, adipose tissue and
      pancreatic beta cells. Further studies are required to confirm this unique
      property of pitavastatin and to understand the mechanism(s) leading to this
      effect. 

PMID- 25575404
TI  - Hidradenitis Suppurativa: A Case Study.

PMID- 25575405
TI  - Esmolol added in repeated, cold, oxygenated blood cardioplegia improves
      myocardial function after cardiopulmonary bypass.
AB  - OBJECTIVE: This study investigated if the beta-receptor blocking agent esmolol,
      added to standard oxygenated blood cardioplegia, improved myocardial function
      after weaning from bypass. DESIGN: A block-randomized, blinded study. SETTING: A
      university laboratory. PARTICIPANTS: Twenty anesthetized pigs, Norwegian
      Landrace. INTERVENTIONS: After cardiopulmonary bypass, cardiac arrest was induced
      with cold (12 degrees C), oxygenated blood cardioplegia, enriched with either
      esmolol or vehicle, repeated every 20 minutes. After 100 minutes the heart was
      reperfused and weaned. MEASUREMENTS AND MAIN RESULTS: Left ventricular function
      was evaluated with pressure-volume loops, local myocardial function with
      multilayer strain and strain rate by epicardial short-axis tissue Doppler
      imaging. One hour after declamping, preload recruitable stroke work did not
      differ between groups, but increased to 72+/-3 mmHg in esmolol-treated animals v
      57+/-4 mmHg (p<0.001) in controls after 3 hours. Radial peak ejection strain rate
      also was increased by esmolol; 6.0+/-1.0 s(-1)v 2.9+/-0.3 s(-1) (p<0.001) in
      subendocardium and 3.9+/-0.5 s(-1)v 2.3+/-0.2 s(-1) (p<0.005) in the
      midmyocardium. Cardiac index was increased, 4.0+/-0.2 L/min/m(2) by esmolol v
      3.3+/-0.1 L/min/m(2) for controls (p<0.05). Isovolumetric relaxation time
      constant was reduced by esmolol, 23+/-1 ms v 26+/-1 ms (p<0.025). Troponin-T did
      not differ and was 339+/-48 ng/L for the esmolol group and 357+/-55 ng/L for the
      control group (p = 0.81). CONCLUSIONS: Esmolol added to blood cardioplegia
      preserved systolic cardiac function during the first 3 hours after reperfusion in
      a porcine model with 100 minutes of cardioplegic arrest.

PMID- 25575407
TI  - Focused Echocardiography During Glucagon Administration to Diagnose Beta-Blocker
      Induced Cardiomyopathy.

PMID- 25575406
TI  - The development of a perioperative echocardiography consult service: the Nebraska
      experience.

PMID- 25575409
TI  - Validation of the Intensive Care National Audit and Research Centre Scoring
      System in a UK Adult Cardiac Surgery Population.
AB  - OBJECTIVE: The Intensive Care National Audit and Research Centre (ICNARC) scoring
      system was conceived in 2007, utilizing 12 physiologic variables taken from the
      first 24 hours of adult admissions to the general intensive care unit (ICU) to
      predict in-hospital mortality. The authors aimed to evaluate the ICNARC score in
      predicting mortality in cardiac surgical patients compared to established cardiac
      risk models such as logistic EuroSCORE as well as to the Acute Physiology and
      Chronic Health Evaluation (APACHE) II. DESIGN: Retrospective analysis of data
      collected prospectively. SETTING: Single-center study in a cardiac intensive care
      in a regional cardiothoracic center. PARTICIPANTS: Patients undergoing cardiac
      surgery between January 2010 and June 2012. METHODS: A total of 1,646 patients
      were scored preoperatively using the logistic EuroSCORE and postoperatively using
      ICNARC and APACHE II. Data for comparison of scoring systems are presented as
      area under the receiver operating characteristic curve. MEASUREMENTS AND MAIN
      RESULTS: The mean age at surgery was 67 years+/-10.1. The mortality from all
      cardiac surgery was 3.2%. The mean logistic EuroSCORE was 7.31+/-10.13, the mean
      ICNARC score was 13.42+/-5.055, while the mean APACHE II score was 6.32+/-7.731.
      The c-indices for logistic EuroSCORE, ICNARC, and APACHE II were 0.801, 0.847 and
      0.648, respectively. CONCLUSION: The authors have, for the first time, validated
      the ICNARC score as a useful predictor of postoperative mortality in adult
      cardiac surgical patients. This could have implications for postoperative
      management, focusing the utilization of resources as well as a method to measure
      and compare performance in the cardiothoracic ICU.

PMID- 25575408
TI  - Acute Kidney Injury and Long-term Risk of Cardiovascular Events After Cardiac
      Surgery: A Population-Based Cohort Study.
AB  - OBJECTIVE: To examine the impact of postoperative acute kidney injury (AKI) on
      the long-term risk of myocardial infarction, heart failure, stroke, and all-cause
      mortality after elective cardiac surgery. The authors investigated whether time
      of onset of AKI altered the association between AKI and the adverse events.
      DESIGN: Population-based cohort study in 2006-2011. SETTING: Two university
      hospitals. PARTICIPANTS: Adult elective cardiac surgical patients. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: AKI was defined as an increase in baseline
      creatinine according to the Kidney Disease Improving Global Outcomes criteria.
      AKI was defined within 30 days of surgery, and also analyzed as early- or late
      onset AKI. The authors followed patients from postoperative day 30 until
      hospitalization with myocardial infarction, heart failure, stroke, or death.
      Adjustment for confounding factors was done using propensity scores and
      standardized-mortality-ratio weights. A total of 1,457 (30.7%) of 4,742 patients
      developed AKI within 30 days of surgery and 470 (9.9%) patients experienced a
      composite cardiovascular endpoint. Comparing patients with and without
      postoperative AKI, weighted hazard ratio (HR) and 95% confidence intervals (CI)
      of 5-year risk of the composite cardiovascular endpoint was 1.41 (95% CI: 1.11
      1.80). For each endpoint separately the weighted HR was similarly increased.
      Ninety-one days to 5-year weighted HR of all-cause mortality was 1.37 (95% CI:
      1.05-1.80). The effect of AKI was similar for early- and late-onset AKI.
      CONCLUSIONS: Early- and late-onset AKI within 30 days of elective cardiac surgery
      was associated with a similarly increased 5-year risk of myocardial infarction,
      heart failure, stroke, and increased all-cause mortality.

PMID- 25575410
TI  - Central Venous-Arterial pCO2 Difference Identifies Microcirculatory Hypoperfusion
      in Cardiac Surgical Patients With Normal Central Venous Oxygen Saturation: A
      Retrospective Analysis.
AB  - OBJECTIVE: Parameters such as central venous oxygen saturation (ScvO2) are used
      increasingly to monitor adequate hemodynamic treatment. However, it still remains
      challenging to identify patients with assumed adequate circulatory status
      quantified by ScvO2 who suffer from macro- and microcirculatory hypoperfusion.
      The authors hypothesized that central venous-arterial pCO2 difference (dCO2)
      could serve as an additional parameter to evaluate the adequacy of perfusion in
      cardiac surgery patients. DESIGN: Retrospective data analysis of a prospective
      interventional study. SETTING: University medical center. PARTICIPANTS: Patients
      undergoing surgery with cardiopulmonary bypass. INTERVENTIONS: The dCO2 was
      measured postoperatively. The patients with an ScvO2>=70% were divided into 2
      groups, the high-dCO2 group (>=8 mmHg) and the low-dCO2 group (<8 mmHg).
      MEASUREMENTS AND MAIN RESULTS: Sixty patients were included in this analysis.
      Twenty-five patients had ScvO2>=70%, 4 patients were assigned to the high-dCO2
      group. Patients of the high-dCO2 group had significantly longer intensive care
      unit (ICU) stays (4 d; 1-29 v 1 d; 1-1; p = 0.02), significantly prolonged need
      for mechanical ventilation (41.5 h; 11-263.5; v 10 h; 7-11; p = 0.03), and higher
      cardiovascular complication rates in the ICU on postoperative days 3, 4, and 5 (p
      = 0.02). The mixed venous saturation (SvO2) after 1 hour in the ICU was
      significantly lower, lactate levels were significantly higher, and the plasma
      disappearance rate of indocyanine green was significantly lower after 1 hour in
      the ICU (14.6%/min; 11.6-19.8%/min v 23.6%/min; 22.5-27.3%/min; p = 0.02) in the
      high-dCO2 group. Cytokines increased significantly postoperatively in the high
      dCO2 group. CONCLUSIONS: The authors described dCO2 as a routinely available tool
      to detect global and microcirculatory hypoperfusion in postoperative cardiac
      surgical patients. The authors showed that in patients with an ScvO2>=70%, a high
      dCO2 (>=8 mmHg) was associated with increased postoperative lactate levels and
      decreased splanchnic function. These findings were associated with a longer need
      for mechanical ventilation and longer ICU stay.

PMID- 25575411
TI  - Initial clinical experience with a miniaturized transesophageal echocardiography
      probe in a cardiac intensive care unit.
AB  - OBJECTIVE: To investigate the safety of a novel, miniaturized, monoplane
      transesophageal echocardiography probe (mTEE) and its potential as a hemodynamic
      monitoring tool. DESIGN: This was a retrospective analysis of the clinical
      evaluation of a disposable mTEE in ventilated patients with severe cardiogenic
      shock requiring hemodynamic support. mTEE assessment was performed by operators
      with mixed levels of TEE training. Information on hemodynamic interventions based
      on mTEE findings was recorded. SETTING: A tertiary university cardiac critical
      care unit. PARTICIPANTS: Male and female critical care patients admitted to the
      unit with severe hemodynamic instability. INTERVENTIONS: Insertion of
      miniaturized disposable TEE probe and hemodynamic and other critical care
      interventions based on this and conventional monitoring. MEASUREMENTS AND MAIN
      RESULTS: In 41 patients (51.2% female, 73.2% after cardiac surgery), hemodynamic
      support probe insertion was accomplished without major complications. A total of
      195 mTEE studies were performed, resulting in changes in therapy in 37 (90.2%)
      patients based on mTEE findings, leading to an improvement in hemodynamic
      parameters in 33 (80.5%) patients. Right ventricular (RV) failure was diagnosed
      in 25 patients (67.6%) and mTEE had a direct therapeutic impact on management of
      RV failure in 17 patients (68 %). CONCLUSIONS: Insertion and operation of a
      novel, miniaturized transoesophageal echocardiography probe can be performed for
      up to 72 hours without major complications. Repeated assessment using this device
      provides complementary information to invasive monitoring in the majority of
      patients and has an impact on hemodynamic management.

PMID- 25575412
TI  - Sentinel physician's network in Reunion Island: a tool for infectious diseases
      surveillance.
AB  - The surveillance of infectious diseases in Reunion Island is based on a sentinel
      network of family physicians (FPs) coordinated by the Indian Ocean regional
      institute for public health surveillance (French acronym OI Cire). The objectives
      are to identify and monitor outbreaks of influenza, gastroenteritis, and chicken
      pox, and to characterize circulating influenza viruses. The network can monitor
      other potentially epidemic diseases. METHOD: The Reunion sentinel network ensures
      a continuous and permanent surveillance. Physicians send their weekly activity
      data to the Cire that collects, processes, and interprets it; they also collect
      samples for biological surveillance of influenza. Statistical thresholds, based
      on historical data and the estimated numbers of incident cases, are calculated to
      follow the trend, detect outbreaks, and quantify their impact. RESULTS: The
      network currently includes 56 FPs and pediatricians, accounting for 6.5% of FPs
      on the island. The network has clarified the seasonality of influenza during the
      austral winter and identified the seasonality of acute diarrhea with an epidemic
      peak when school starts in August. The sentinel FPs's reports allowed monitoring
      the epidemic trend and estimating the number of cases during the 2005 and 2006
      chikungunya outbreaks and 2009 influenza A (H1N1) outbreaks. CONCLUSION: The
      network has proven its contribution, responsiveness, and reliability for
      epidemiological surveillance during outbreak. It is an essential tool for
      infectious diseases surveillance in Reunion Island.

PMID- 25575413
TI  - Long-term increased factor VIII levels are associated to interleukin-6 levels but
      not to post-thrombotic syndrome in patients with deep venous thrombosis.
AB  - INTRODUCTION: Increased FVIII levels are a well established risk factor for deep
      venous thrombosis (DVT), whose etiopathogenesis is not yet well understood. In
      this study, we aimed to evaluate the possibility that inflammatory markers and
      post-thrombotic syndrome (PTS) could contribute to FVIII levels in patients with
      a history of DVT. DESIGN AND METHODS: It is a case-control study that included 68
      patients with DVT of the lower limbs 32 months after the acute episode, and 67
      healthy adults as controls. We evaluated plasma levels of FVIII, VWF, D-dimer and
      serum levels of CRP, IL-6, IL-8, TNF-alpha in patients and controls. The presence
      of PTS was evaluated by the Villalta scale. RESULTS: Patients with DVT presented
      higher levels of FVIII, VWF and D-dimer when compared to controls (P <= 0.001).
      Almost 50% of patients presented FVIII levels above 90th percentile. Furthermore,
      IL-6 (1.19 vs. 0.98 pg/mL, P = 0.01) and TNF-alpha (2.27 vs. 1.57 pg/mL, P <=
      0.001) were also higher in patients when compared to controls. In a linear
      regression multivariate model, VWF and IL-6 levels were independent factors
      associated with FVIII levels (P <= 0.001). FVIII levels were not increased in
      patients with PTS. Patients with PTS showed higher levels of IL-8 when compared
      to patients without PTS (23.03 vs. 18.20 pg/mL, P = 0.04). CONCLUSIONS: In
      conclusion, we demonstrated that DVT is associated with increased levels of
      inflammatory and coagulation markers, including FVIII, even a long time after the
      acute episode. Moreover, IL-6 levels were an independent factor associated with
      FVIII levels. Finally, PTS seems to be related to inflammatory cytokine IL-8, a
      proinflammatory and proangiogenic chemokine, but not to FVIII levels.

PMID- 25575414
TI  - Accuracy of inverse treatment planning on substitute CT images derived from MR
      data for brain lesions.
AB  - BACKGROUND: In this pilot study we evaluated the performance of a substitute CT
      (s-CT) image derived from MR data of the brain, as a basis for optimization of
      intensity modulated rotational therapy, final dose calculation and derivation of
      reference images for patient positioning. METHODS: S-CT images were created using
      a Gaussian mixture regression model on five patients previously treated with
      radiotherapy. Optimizations were compared using D max, D min, D median and D mean
      measures for the target volume and relevant risk structures. Final dose
      calculations were compared using gamma index with 1%/1 mm and 3%/3 mm acceptance
      criteria. 3D geometric evaluation was conducted using the DICE similarity
      coefficient for bony structures. 2D geometric comparison of digitally
      reconstructed radiographs (DRRs) was performed by manual delineation of relevant
      structures on the s-CT DRR that were transferred to the CT DRR and compared by
      visual inspection. RESULTS: Differences for the target volumes in optimization
      comparisons were small in general, e.g. a mean difference in both D min and D max
      within +/-0.3%. For the final dose calculation gamma evaluations, 100% of the
      voxels passed the 1%/1 mm criterion within the PTV. Within the entire external
      volume between 99.4% and 100% of the voxels passed the 3%/3 mm criterion. In the
      3D geometric comparison, the DICE index varied between approximately 0.8-0.9,
      depending on the position in the skull. In the 2D DRR comparisons, no appreciable
      visual differences were found. CONCLUSIONS: Even though the present work involves
      a limited number of patients, the results provide a strong indication that
      optimization and dose calculation based on s-CT data is accurate regarding both
      geometry and dosimetry.

PMID- 25575415
TI  - Methyl jasmonate elicits the production of methyl (E)-2-hexenoate from (Z)-2
      hexenol via (Z)-2-hexenal in Achyranthes bidentata plant.
AB  - The medicinal herbal plant Achyranthes bidentata (A. bidentata) produces the
      sweet-odor ester - methyl (E)-2-hexenoate (1) as the major volatile in response
      to methyl jasmonate (MeJA). Here, we investigated the biosynthetic pathway of
      methyl (E)-2-hexenoate (1). The common plant precursor (Z)-3-hexenal was only
      slightly metabolized into methyl (E)-2-hexenoate (1), and its application
      scarcely enhanced the production of this ester. By contrast, a structurally
      related alcohol, (Z)-2-hexenol, as well as a deuteride derivative thereof could
      be efficiently metabolized into methyl (E)-2-hexenoate (1). Thus, we hypothesize
      that A. bidentata possess a specific pathway for the production of methyl (E)-2
      hexenoate (1) from (Z)-2-hexenol in response to MeJA. 

PMID- 25575417
TI  - [TINU syndrome: report of 3 cases].

PMID- 25575416
TI  - A high-throughput screening assay for identification of inhibitors of the A1AO
      ATP synthase of the rumen methanogen Methanobrevibacter ruminantium M1.
AB  - We report the development of a high-throughput screening platform to identify
      inhibitors of the membrane-bound A1Ao-ATP synthase from the rumen methanogen
      Methanobrevibacter ruminantium M1. Inhibitors identified in the screen were
      tested against growing cultures of M. ruminantium, validating the approach to
      identify new inhibitors of methanogens. 

PMID- 25575418
TI  - [New neuroretinal rim analysis with spectral domain optical coherence tomography,
      Spectralis (Heidelberg Engineering, Germany). Preliminary study].
AB  - INTRODUCTION: Clinical determination of the outer limits of the optic disk (OD)
      doesn't always correspond to the true anatomic limits of the optic nerve head
      (ONH) defined by the Bruch's membrane opening (BMO). A new index analyzing the OD
      with optical coherence tomography (OCT), "minimal rim width" (BMO-MRW), evaluates
      the smallest thickness of the neuroretinal rim between the BMO and the internal
      limiting membrane. The purpose of this study was to evaluate new software for
      automatic measurement of the BMO-MRW. MATERIALS AND METHODS: This study
      investigated 95 eyes: 40 control eyes and 55 eyes followed and treated for
      primary open angle glaucoma (42 early glaucoma, 7 moderate glaucoma and 6
      advanced glaucoma). After a precise localization of the OD center, 24 radial
      scans of the ONH are taken with the Spectralis OCT (Heidelberg Engineering,
      Germany). From the 48 measurements of BMO-MRW, the mean thickness as well as that
      in each of the 6 papillary sectors of this new index are calculated. ROC curves
      analysis (receiver operating characteristic) was used to assess the diagnostic
      capabilities of the various parameters. RESULTS: Thicknesses of all parameters
      were statistically lower in glaucoma than in controls. The mean value and
      inferotemporal sector (IT) had the best diagnostic capabilities without
      significant difference between them (BMO-MRW-average = 0.890 +/- 0.062, BMO-MRW
      IT = 0.881 +/- 0.066, P = 0.59). The area under the curve was lowest in the
      temporal sector (0.820 +/- 086 statistically lower than the average value, P =
      0.04). CONCLUSIONS: This preliminary study of a new automated analysis of the
      neuroretinal rim highlights the diagnostic value of the BMO-MRW index. This
      evaluation appears to be best correlated with the anatomy of the ONH with good
      diagnostic sensitivity.

PMID- 25575421
TI  - Healthcare utilization by obese and overweight children.
AB  - OBJECTIVE: To examine the relationship between childhood obesity and health care
      use in a large, nationally representative group of children with measured
      anthropometrics. STUDY DESIGN: Analysis of 5 combined National Health and
      Nutrition Survey datasets from 2001 to 2010. Unadjusted and adjusted logistic
      regression models assessed the relationship between health care use variables and
      weight status (overweight: body mass index 85th to <95th percentile for age and
      sex; obese: body mass index >=95th percentile for age and sex) for children 2-18
      years of age. RESULTS: Overweight and obese children are more likely to receive
      their routine medical care in an emergency department than a primary care setting
      (overweight OR 1.95; 95% CI 1.22-3.14 and obese OR 1.88; 95% CI 1.24-2.86) than
      their normal-weight peers. After we adjusted for relevant covariates, this
      finding persisted among overweight, but not obese, children. Other health care
      use variables were not significantly associated with weight status. CONCLUSION:
      Overweight children may be more likely to use the emergency department than
      primary care settings for routine medical care. Interventions to establish
      primary care medical homes for overweight children merit consideration.

PMID- 25575420
TI  - Functional outcomes at age 7 years of moderate preterm and full term children
      born small for gestational age.
AB  - OBJECTIVE: To compare functional outcomes of 7-year-old (school-age) children
      born small for gestational age (SGA; ie, a birth weight z score <= -1 SD), with
      appropriate for gestational age (AGA) peers, born moderately preterm or full
      term. STUDY DESIGN: Data were collected as part of the Longitudinal Preterm
      Outcome Project study, a community-based, prospective cohort study of 336 AGA and
      42 SGA born children (median gestational age 35 weeks, range 31-41). Of the SGA
      children, 32 were moderately preterm, 10 were full term; of the AGA, these
      numbers were 216 and 120, respectively. At 6.9 years, we assessed intelligence,
      verbal memory, attention, visuomotor integration, and motor skills and we
      collected the parent-reported executive functioning. We compared the outcomes of
      the SGA children with those of their AGA peers. RESULTS: The performance of SGA
      children was similar to that of their AGA peers, except for attention control
      which was abnormal more often in SGA children (OR 3.99, 95% CI 1.32-12.12). The
      IQ of SGA children was 3 points lower, but this difference failed to reach
      significance. CONCLUSIONS: At school age, children born SGA have a greater risk
      of abnormal test scores on attention control than children born AGA, independent
      of gestational age. Their motor and many other cognitive functions are similar.
      The impact of these outcomes seems limited. Nevertheless, the consequences for
      school performance deserve attention.

PMID- 25575419
TI  - [DSAEK after failed penetrating keratoplasty].
AB  - PURPOSE: To report the anatomic and functional outcomes of Descemet's stripping
      automated endothelial keratoplasty (DSAEK) in 32 eyes after failed penetrating
      keratoplasty (PK). SUBJECTS AND METHODS: This retrospective, single-center
      observational study was performed on 32 eyes of 26 patients with failed PK grafts
      who underwent DSAEK between June 2009 and June 2013 at Clermont-Ferrand
      University Medical Center. Primary outcomes measured were: graft survival rates,
      functional improvement (visual acuity), and complications. RESULTS: Mean follow
      up was 16.45 months [6-36]. Graft survival at 12 months was 76.1 % [68.1-82.3].
      PK grafts cleared in 75 % of cases. Eight primary DSAEKs detached and/or
      decentered early (prior to day 8, average 6.22 days): 3 underwent repeat DSAEK
      with a new graft, and 3 underwent conversion to PK. Results were available for 26
      patients at 6 months. Mean preoperative best-corrected visual acuity (BCVA) in
      logMAR increased from 1.48 (counting fingers at 2 meters) to 0.996 logMAR (1/10)
      at 6 months. BCVA improved in 17 patients (68 %). BCVA improved an average of 5.2
      lines (P=0.0006). Eight patients had a large number of comorbid conditions that
      limited final visual acuity. DISCUSSION: Anatomic outcomes are similar to other
      studies. Final average BCVA was limited by severe comorbid conditions and
      performance of DSAEK solely for comfort. Many surgical strategies have been
      described to decrease graft dislocation and primary graft failure. Adapting graft
      trephine diameter to the host cornea as measured by AS-OCT, using a nomogram
      based on posterior corneal curvature obtained on AS-OCT, may be an interesting
      approach. CONCLUSION: DSAEK allows for quick visual recovery by preserving the
      anterior corneal curvature. It is an essential option for restoring corneal
      clarity in PK failure due to endothelial decompensation. A longer follow-up would
      allow a comparison of graft survival for the two techniques in this context.

PMID- 25575423
TI  - Fever is common postoperatively following posterior spinal fusion: infection is
      an uncommon cause.
AB  - OBJECTIVE: To determine the frequency and clinical significance of postoperative
      fever in pediatric patients undergoing posterior spinal fusion (PSF). STUDY
      DESIGN: A retrospective chart review was performed for consecutive patients
      undergoing PSF at a single institution between June 2005 and April 2011, with a
      minimum of 2-year follow up. Exclusion criteria were previous spine surgery, a
      combined anterior-posterior approach, and delayed wound closure at the time of
      surgery. RESULTS: Two hundred and seventy-eight patients with an average age of
      13 years (1-22 years) met inclusion criteria, with the following diagnoses:
      adolescent idiopathic scoliosis 43%, neuromuscular/syndromic scoliosis 39%,
      congenital scoliosis 11%, spondylolisthesis 4%, and Scheuermann kyphosis 3%.
      Seventy-two percent (201/278) of patients had a maximum temperature (Tmax) >38(
      degrees ) postoperatively, and 9% (27/278) Tmax >39( degrees ). The percentage of
      febrile patients trended down following the first postoperative day. Infection
      rate was 4% (12/278). There was no correlation between Tmax >38( degrees ) or
      Tmax >39( degrees ), and timing of fever, positive blood or urine cultures,
      pneumonia, or surgical site infection. CONCLUSION: Seventy-two percent of
      pediatric patients undergoing PSF experienced postoperative fever, and 9% of
      patients had Tmax>39( degrees ). There was no significant correlation between
      fever and positive blood culture, urine culture, pneumonia, or surgical site
      infection. This information may help relieve stress for families and healthcare
      providers, and obviate routine laboratory evaluation for fever alone.

PMID- 25575424
TI  - Mode of delivery and outcomes by birth weight among spontaneous and induced
      singleton cephalic nulliparous labors.
AB  - OBJECTIVE: To assess the effect of birth weight on mode of delivery among
      nulliparous women in a setting with no policy of elective induction for suspected
      macrosomia. METHODS: In an observational study, data were assessed from
      nulliparous women with a single cephalic pregnancy of at least 37 weeks in
      spontaneous (Robson group 1) and induced (Robson group 2a) labor attending a
      hospital in Dublin, Ireland, between January 1, 2008, and December 31, 2009. The
      primary outcome measure was mode of delivery. RESULTS: A total of 7528
      nulliparous labors were included (4989 in group 1 and 2539 in group 2a). The
      cesarean section rate was 15.1% overall (n=1139), with 411 (8.2%) in group 1, and
      728 (28.7%) in group 2a. Cesarean delivery rates rose with increasing birth
      weight in group 1, from 119 (6.3%) of 1886 infants weighing 3000-3499 g and 160
      (8.5%) of 1892 weighing 3500-3999 g, to 19 (26.8%) of 71 weighing 4500-4999 g.
      Rates of cesarean delivery were significantly higher in induced labor (group 2a)
      for each birth-weight category, ranging from 202 (25.9%) of 781 weighing 3000
      3499 g and 243 (27.0%) of 899 weighing 3500-3999 g, to 38 (48.1%) of 79 weighing
      4500-4999 g (P<0.01 for all). CONCLUSION: In a setting with standardized
      management of labor, birth weight remains a significant determinant of mode of
      delivery.

PMID- 25575422
TI  - Poor head growth as a presenting sign of a cortisol-secreting adrenal adenoma in
      a 2-year-old boy.
AB  - Typical signs of glucocorticoid excess in children are weight gain and poor
      linear growth. We describe a 2-year-old boy with a cortisol-secreting adenoma who
      presented with a dramatic decline in head growth. This case underscores concern
      of adverse effects of excess glucocorticoid on brain growth in very young
      children. 

PMID- 25575425
TI  - Complications of adenotonsillectomy for obstructive sleep apnea in school-aged
      children.
AB  - INTRODUCTION: Adenotonsillectomy is the treatment of choice for most children
      with obstructive sleep apnea syndrome, but can lead to complications. Current
      guidelines recommend that high-risk children be hospitalized after
      adenotonsillectomy, but it is unclear which otherwise-healthy children will
      develop post-operative complications. We hypothesized that polysomnographic
      parameters would predict post-operative complications in children who
      participated in the Childhood AdenoTonsillectomy (CHAT) study. METHODS: Children
      in the CHAT study aged 5-9 years with apnea hypopnea index 2-30/h or obstructive
      apnea index 1-20/h without comorbidities other than obesity/asthma underwent
      adenotonsillectomy. Associations between demographic variables and surgical
      complications were examined with Chi square and Fisher's exact tests.
      Polysomnographic parameters between subjects with/without complications were
      compared using Mann-Whitney tests. RESULTS: Of the 221 children (median apnea
      hypopnea index 4.7/h, range 1.2-27.7/h; 31% obese), 16 (7%) children experienced
      complications. 3 (1.4%) children had respiratory complications including
      pulmonary edema, hypoxemia and bronchospasm. Thirteen (5.9%) had non-respiratory
      complications, including dehydration (4.5%), hemorrhage (2.3%) and fever (0.5%).
      There were no statistically significant associations between demographic
      parameters (gender, race, and obesity) or polysomnographic parameters (apnea
      hypopnea index, % total sleep time with SpO2<92%, SpO2 nadir, % sleep time with
      end-tidal CO2>50Torr) and complications. CONCLUSIONS: This study showed a low
      risk of post-adenotonsillectomy complications in school-aged healthy children
      with obstructive apnea although many children met published criteria for
      admission due to obesity, or polysomnographic severity. In this specific
      population, none of the polysomnographic or demographic parameters predicted post
      operative complications. Further research could identify the patients at greatest
      risk of post-operative complications.

PMID- 25575426
TI  - Patient selection in congenital pyriform aperture stenosis repair - 14 year
      experience and systematic review of literature.
AB  - PURPOSE: Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of
      respiratory distress in neonates that may necessitate early surgical
      intervention. Restenosis and granulation are postoperative concerns that may
      prompt a return to the operating room. Reoperation places children at increased
      risk of perioperative complications and prolonged hospital stays. We are
      presenting a review of our institutional experience of 16 patients treated for
      CNPAS over a 14 year period and a systematic review with pooled data analysis to
      determine the effect of craniofacial and neurologic anomalies on surgical
      success. METHODS: Retrospective chart review of all cases of CNPAS treated at our
      tertiary children's hospital between 1999 and 2013. Systematic review of English
      language literature was conducted adhering to the PRISMA statement to determine
      the effect of neurologic anomalies and craniofacial dysmorphism (CFD) on surgical
      failure for CNPAS treatment. Univariate and exact multiple logistic regression
      were used for analysis of an individual patient data analysis. RESULTS: 10
      patients had surgery and 6 were treated medically. Average pyriform apertures
      were 5.71+/-1.72mm for the surgical group and 4.83+/-1.26mm for the medical group
      (p=0.38). 31% had neurological impairments. 31% had craniofacial dysmorphisms
      (CFD). 2 patients developed restenosis and 1 required tracheotomy. Both of these
      patients had other CFDs. Literature review captured 63 surgical patients and 9
      failures in 6 series of CNPAS. 4.6% of patients without CFD and 36.8% of patients
      with CFD required surgical revision (p=0.023, OR13.8). CONCLUSION: When repairing
      CNPAS, co-morbidities must be considered. Impaired respiration, central
      neurologic deficits and extensive craniofacial anomalies may require additional
      surgeries or an alternative approach.

PMID- 25575427
TI  - Does primary indication for tonsillectomy influence post-tonsillectomy
      haemorrhage rates in children?
AB  - INTRODUCTION: A significant risk in tonsillectomy that causes concern to surgeon
      and patient is post-tonsillectomy bleed. Secondary haemorrhage is mainly post
      operative bleed presenting at or 24h after surgery. Classical teaching indicates
      infection as the cause. There are not enough published data to evaluate the post
      tonsillectomy bleed rates in patients operated for obstructive sleep apnoea
      versus recurrent tonsillitis. We suspected secondary bleed rates to be higher in
      patients with recurrent tonsillitis. METHODS: A retrospective review of case
      notes of patients presenting to Accident & Emergency department within 4 weeks of
      tonsillectomy or adeno-tonsillectomy was performed. 568 patients presented with
      post-operative complications over the 5-year period 2008-2013. Of these, 222
      presented with post-operative secondary bleed. Electronic case records were used
      to identify indication of operation and matched with coding data. These coded
      data were also used to identify number of operations and primary indications over
      the 5-year period. RESULTS: The proportion of OSA patients receiving
      tonsillectomy or adenotonsillectomy surgery increased over the 5-year period.
      Secondary haemorrhage rate for recurrent tonsillitis surgery was around 4.9% and
      for OSA surgery was around 15.6%. Comparison of recurrent tonsillitis against OSA
      for post-operative bleed showed a relative risk of 0.31 (CI 0.24-0.41). The
      incidence of bleeding mirrored primary indication for each year. CONCLUSION: The
      bleed rate for OSA was unexpectedly higher than for recurrent tonsillitis. The
      primary indication for tonsillectomy affects secondary bleeding rate.

PMID- 25575428
TI  - PrEP in substance abuse treatment: a qualitative study of treatment provider
      perspectives.
AB  - OBJECTIVES: To examine substance abuse treatment providers' views on engaging
      clients in Pre-exposure Prophylaxis (PrEP) care and research trials. METHODS:
      Thirty-six medical and counseling service providers in six New York City
      outpatient substance abuse treatment programs participated in semi-structured
      qualitative interviews. Thematic content analysis was conducted by three coders,
      independently. RESULTS: Providers' perspectives toward PrEP were characterized by
      six salient themes: 1) Limited PrEP awareness. 2) Ambivalence about PrEP; 3)
      Perception of multiple challenges to delivery; 4) Uncertainty about clients'
      ability to be adherent to medication; 5) Concerns about medication safety/side
      effects; and 6) Perception of multiple barriers to conducting clinical trials.
      CONCLUSIONS: Despite anticipated challenges, providers supported the introduction
      of PrEP in outpatient substance abuse treatment. Comprehensive training for
      providers is needed and should include PrEP eligibility criteria, strategies to
      support adherence and medication monitoring guidelines. Linkages between
      substance abuse treatment and primary care and/or enhancement of capacity within
      clinics to offer PrEP may help facilitate PrEP delivery. When conducting research
      in outpatient clinics, it is particularly important to protect client
      confidentiality.

PMID- 25575429
TI  - Anthropometrics indices of obesity, and all-cause and cardiovascular disease
      related mortality, in an Asian cohort with type 2 diabetes mellitus.
AB  - AIM: The study investigated the relationship of general (body mass index [BMI])
      and central (waist circumference [WC]; waist-hip ratio [WHipR]; waist-height
      ratio [WHeightR]) adiposity with all-cause and cardiovascular disease (CVD)
      related mortality in an Asian population with diabetes. METHODS: A total of
      13,278 participants with type 2 diabetes mellitus (T2DM) recruited from public
      sector primary-care and specialist outpatients clinics in Singapore were followed
      up for a median duration of 2.9 years, during which time there were 524 deaths.
      Cox proportional-hazards regression and competing-risk models were used to obtain
      hazard ratios (HRs) for anthropometric variables of all-cause and CVD-related
      mortality. RESULTS: After adjusting for BMI, the highest quintiles of WC, WHipR
      and WHeightR were all positively associated with mortality compared with the
      lowest quintiles, with WHeightR exhibiting the largest effect sizes [all-cause
      mortality HR: 2.13, 95% confidence interval (CI): 1.33-3.42; CVD-related
      mortality HR: 3.42, 95% CI: 1.62-7.19]. Being overweight but not obese
      (BMI:>=23.0 but<27.5kg/m(2)) was associated with a decreased risk of CVD-related
      mortality in those aged>=65 years (HR: 0.47, 95% CI: 0.29-0.75), but not in those
      aged<65 years (HR: 1.11, 95% CI: 0.49-2.50). CONCLUSION: Overweight, but not
      obesity, was associated with a reduction in risk of mortality. This was seen in
      T2DM patients aged>=65 years, but not in those younger than this. At the same
      BMI, having higher central-obesity indices such as WC, WHipR and WHeightR also
      increased the risk of mortality.

PMID- 25575430
TI  - Histamine restores biliary mass following carbon tetrachloride-induced damage in
      a cholestatic rat model.
AB  - BACKGROUND: Bile duct ligation coupled with carbon tetrachloride induces
      apoptosis of large but not small cholangiocytes. Histidine decarboxylase
      regulates histamine synthesis. We have shown that: (i) cholangiocytes express
      histidine decarboxylase and secrete histamine and (ii) histamine stimulates
      biliary growth. AIMS: To demonstrate that histidine decarboxylase/histamine
      regulates cholangiocyte homeostasis after carbon tetrachloride treatment.
      METHODS: In vivo, normal and bile duct ligated rats were treated with saline or
      histamine (0.5mg/kg body weight) and given carbon tetrachloride by gavage 2 days
      before sacrifice. Serum, liver blocks and large cholangiocytes were obtained.
      Histidine decarboxylase, bile duct mass and proliferation were measured in liver
      sections and in cholangiocytes. Apoptosis was measured by immunohistochemistry
      and gene expression. Histamine levels were evaluated in serum. In vitro, large
      cholangiocytes were treated with carbon tetrachloride in the absence/presence of
      histamine before evaluating proliferation. RESULTS: After bile duct ligation
      there was enhanced ductal mass, histidine decarboxylase expression and serum
      histamine levels. Carbon tetrachloride treatment enhanced biliary apoptosis, and
      decreased histidine decarboxylase and serum histamine levels and biliary
      proliferation, changes that were restored by histamine. In vitro, cholangiocytes
      treated with carbon tetrachloride had a lower proliferative capacity that was
      reversed when cells were pre-treated with histamine. CONCLUSION: Histidine
      decarboxylase may be a key regulator of cholangiocyte homeostasis during biliary
      injury.

PMID- 25575431
TI  - A cost-effectiveness model to personalize antiviral therapy in naive patients
      with genotype 1 chronic hepatitis C.
AB  - BACKGROUND AND AIMS: Rapid virologic response is the best predictor of sustained
      virologic response with dual therapy in genotype-1 chronic hepatitis C, and its
      evaluation was proposed to tailor triple therapy in F0-F2 patients. Bio
      mathematical modelling of viral dynamics during dual therapy has potentially
      higher accuracy than rapid virologic in the identification of patients who will
      eventually achieve sustained response. Study's objective was the cost
      effectiveness analysis of a personalized therapy in naive F0-F2 patients with
      chronic hepatitis C based on a bio-mathematical model (model-guided strategy)
      rather than on rapid virologic response (guideline-guided strategy). METHODS: A
      deterministic bio-mathematical model of the infected cell dynamics was validated
      in a cohort of 135 patients treated with dual therapy. A decision-analytic
      economic model was then developed to compare model-guided and guideline-guided
      strategies in the Italian setting. RESULTS: The outcomes of the cost
      effectiveness analysis with model-guided and guideline-guided strategy were 19.1
      19.4 and 18.9-19.3 quality-adjusted-life-years. Total per-patient lifetime costs
      were ?25,200-?26,000 with model-guided strategy and ?28,800-?29,900 with
      guideline-guided strategy. When comparing model-guided with guideline-guided
      strategy the former resulted more effective and less costly. CONCLUSIONS: The
      adoption of the bio-mathematical predictive criterion has the potential to
      improve the cost-effectiveness of a personalized therapy for chronic hepatitis C,
      reserving triple therapy for those patients who really need it.

PMID- 25575432
TI  - The actin-related protein Sac1 is required for morphogenesis and cell wall
      integrity in Candida albicans.
AB  - Candida albicans is a common pathogenic fungus and has aroused widespread
      attention recently. Actin cytoskeleton, an important player in polarized growth,
      protein secretion and organization of cell shape, displays irreplaceable role in
      hyphal development and cell integrity. In this study, we demonstrated a homologue
      of Saccharomyces cerevisiae Sac1, in C. albicans. It is a potential PIP
      phosphatase with Sac domain which is related to actin organization, hyphal
      development, biofilm formation and cell wall integrity. Deletion of SAC1 did not
      lead to insitiol-auxotroph phenotype in C. albicans, but this gene rescued the
      growth defect of S. cerevisiae sac1Delta in the insitiol-free medium. Hyphal
      induction further revealed the deficiency of sac1Delta/Delta in hyphal
      development and biofilm formation. Fluorescence observation and real time PCR (RT
      PCR) analysis suggested both actin and the hyphal cell wall protein Hwp1 were
      overexpressed and mislocated in this mutant. Furthermore, cell wall integrity
      (CWI) was largely affected by deletion of SAC1, due to the hypersensitivity to
      cell wall stress, changed content and distribution of chitin in the mutant. As a
      result, the virulence of sac1Delta/Delta was seriously attenuated. Taken
      together, this study provides evidence that Sac1, as a potential PIP phosphatase,
      is essential for actin organization, hyphal development, CWI and pathogenicity in
      C. albicans. 

PMID- 25575433
TI  - Long-term outcome following advancement flaps for high anal fistulas in an Asian
      population: a single institution's experience.
AB  - BACKGROUND: The management of high anal fistula is often complicated and
      challenging. In spite of numerous new techniques, the advancement flap technique
      remained an integral procedure in its management. The purpose of this study was
      to determine the long-term outcome of advancement flap procedures for high anal
      fistulas. METHODS: A retrospective review of patients who have undergone an
      advancement flap procedure for high anal fistula of cryptoglandular origin from
      June 2003 to April 2012 was performed. Patients were contacted via telephone to
      evaluate their continence status using the Wexner score. RESULTS: Sixty-one
      patients with a median age of 48 (range, 19-74) years and a median follow-up of
      6.5 (range, 1-59) months were evaluated. Fifty-three (86.9 %) patients had
      successful surgery while 8 (13.1 %) failed the procedure. Four of them underwent
      subsequent surgery. Of the 53 patients who had a successful procedure, 27 were
      successfully contacted for a telephone interview. Twenty-one (77.8 %) of them
      reported a Wexner score of '0'. Two (7.4 %) patients had a Wexner score of <4,
      another 2 had a score of '4' and '10', while the last 2 patients had a score of
      >10. CONCLUSION: Advancement flap procedure is effective in the management of
      high anal fistulas with an acceptable success rate. The majority of the patients
      experienced good anal continence.

PMID- 25575434
TI  - Leptin activates cytosolic calcium responses through protein kinase-C dependent
      mechanism in immortalized RFamide-related peptide-3 neurons.
AB  - RFamide-related peptide-3 (RFRP-3), a mammalian ortholog of avian gonadotropin
      inhibitory hormone (GnIH), seems to be an important regulator of the hypothalamus
      pituitary-gonadal (HPG) reproductive axis. Leptin, a permissive hormonal
      regulator of fertility, provides energy signal to brain. According to current
      view, leptin does not act directly on gonadotrophin-releasing hormone (GnRH)
      neurons. RFRP-3 neurons have been shown to express leptin receptors. The goal of
      the present study was to examine whether leptin acts through RFRP-3 neurons to
      modulate activity of the GnRH neurons. For this aim, the effects of leptin on
      intracellular free Ca(2+) levels ([Ca(2+)]i) in RFRP-3 neurons were investigated
      by using in vitro calcium imaging system. In the present study, rHypoE-7 cell
      line was used as a model to explore the effects of leptin on RFRP-3 neurons.
      rHypoE-7 cells were placed on glass coverslip and loaded with 1 MUM Fura-2 AM.
      [Ca(2+)]i responses were quantified by the changes in 340/380 ratio. Leptin (0.1
      10 MUM) caused increases in [Ca(2+)]i in a dose-dependent manner. The changes in
      [Ca(2+)]i were significantly attenuated by pre-treatment with protein kinase C
      inhibitor. These results demonstrate that leptin activates intracellular calcium
      signaling in RFRP-3 neurons through PKC-dependent pathway, and thus leptin may
      exert its effect on GnRH neurons by means of RFRP-3 cells.

PMID- 25575435
TI  - Cattle ticks in Cameroon: is Rhipicephalus (Boophilus) microplus absent in
      Cameroon and the Central African region?
AB  - In most parts of the world, ticks are rapidly developing resistance to commonly
      used acaricides thus rendering control difficult. This constraint is further
      compounded by the introduction of new species in areas where they did not exist
      before. Such is the case with the introduction into and rapid spread of
      Rhipicephalus (Boophilus) microplus in some countries of West Africa. With the
      looming threat of its further spread in the region, the objective of the present
      study was to update knowledge on cattle ticks in Cameroon. Among 19,189 ticks
      collected monthly from 60 animals in 5 herds from March 2012 to February 2013,
      Rh. (B.) decoloratus was the most abundant species with a relative prevalence of
      62.2%, followed by Amblyomma variegatum (28.4%), Rh. (B.) annulatus (0.2%), Rh.
      (B.) geigyi (0.03%), other Rhipicephalus spp. (8.4%) and Hyalomma spp. (0.3%).
      Rh. (B.) decoloratus and A. variegatum were also the most widely distributed in
      space. Infestation rate was generally high, with average tick count/animal of
      about 80 during peak periods. Tick distribution and abundance in the different
      sites was as varied as the underlying factors, among which the most important
      were management systems and climatic factors. The effects of rainfall and
      temperature were confounded by other factors and difficult to evaluate. However,
      it appears tick development depends among other factors, on a humidity threshold,
      above which there is not much more effect. Rh. microplus was not found during
      this study, but more extensive tick collections have to be done to confirm this.
      In conclusion, cattle tick infestation in Cameroon remains an important cause for
      concern. Farmers need assistance in the use and management of acaricides in order
      to increase their efficiency and reduce the development of resistance. Although
      Rh. microplus was not found, its introduction from other West African countries
      is imminent if adequate measures, especially in the control and limitation of
      animal movements, are not taken. 

PMID- 25575436
TI  - Mesenchymal stem cells reside in a vascular niche in the decidua basalis and are
      absent in remodelled spiral arterioles.
AB  - INTRODUCTION: Maternal decidua basalis tissue attached to the placenta following
      delivery is a source of decidual mesenchymal stem cells (DMSCs). The in vitro
      characteristics of DMSCs have been partly defined but their in vivo function(s)
      are poorly understood. The anatomic location, or niche, provides clues regarding
      potential in vivo function(s) of DMSCs, but the niche has not been described.
      METHODS: Cells were isolated from the decidua basalis and flow cytometric
      analyses showed the expected phenotypic profile for MSC cell surface markers. In
      vitro, the cells differentiated into adipocytes, osteocytes, and chondrocytes.
      DMSCs were then stained with antibodies by immunofluorescence detection. RESULTS:
      Immunocytochemistry revealed that DMSCs were positive for FZD-9, STRO-1, 3G5, and
      alpha-SMA as expected and lacked expression of vWF and Ck7. Fluorescence in situ
      hybridization analysis showed the cultured cells were of maternal origin.
      Immunofluorescence was carried out on placental bed biopsies using the FZD-9,
      STRO-1, 3G5, and alpha-SMA antibodies. DMSCs were located in the vascular niche
      in decidua basalis. Immunofluorescence with antibodies to FZD-9, Ck7 and vWF
      revealed DMSCs in the vascular niche surrounding intact non-transformed spiral
      arterioles but DMSCs were absent in fully transformed spiral arterioles.
      DISCUSSION: Spiral arteriole remodelling is a critical feature of human
      pregnancy. The DMSC niche was investigated in fully transformed and non
      transformed spiral arterioles. DMSCs have not been previously implicated in
      spiral arteriole remodelling. The absence of DMSCs around fully transformed
      spiral arterioles suggests they are a target for replacement or destruction by
      invading placental extravillous trophoblast cells, which carry out spiral
      arteriole remodelling.

PMID- 25575437
TI  - Automatic differentiation of placental perfusion compartments by time-to-peak
      analysis in mice.
AB  - INTRODUCTION: The aim of this study was to develop an automatic differentiation
      of two perfusion compartments within the mouse placenta based on times of maximal
      contrast enhancement for a detailed and reproducible perfusion assessment.
      METHODS: Placentas (n = 17) from pregnant BALB/c mice (n = 10) were examined in
      vivo at 7T on gestation day 16.5. Coronal dual-echo 3D T1-weighted gradient-echo
      sequences were acquired after application of contrast agent for dynamic MRI. An
      adapted gamma variate function was fitted to the discrete concentration time
      curves to evaluate the effect of noise on perfusion and segmentation results.
      Time-to-peak maps based on fitted and discrete curves of each placenta were used
      to classify each voxel into the high- or low-blood flow compartment using k-means
      clustering. Perfusion analysis was performed using the steepest slope model and
      also applied to fitted and discrete curves. Results were compared to manually
      defined compartments from two independent observers using the Dice coefficient D.
      RESULTS: Manually defined placental areas of high-flow and low-flow were similar
      to the automatic segmentation for discrete (D = 0.76/0.75; D = 0.76/0.79) and
      fitted (D = 0.80/0.80; D = 0.81/0.82) concentration time curves. Mean perfusion
      values of discrete and fitted curves ranged in the high-flow compartment from 134
      to 142 ml/min/100 ml (discrete) vs. 138-143 ml/min/100 ml (fitted) and in the low
      flow compartment from 91 to 94 ml/min/100 ml (discrete) vs. 74-82 ml/min/100 ml
      (fitted). DISCUSSION: Our novel approach allows the automatic differentiation of
      perfusion compartments of the mouse placenta. The approach may overcome
      limitations of placental perfusion analyses caused by tissue heterogeneity and a
      potentially biased selection of regions of interest.

PMID- 25575438
TI  - Metadherin contributes to the pathogenesis of chronic lymphocytic leukemia
      partially through Wnt/beta-catenin pathway.
AB  - Metadherin (MTDH) is involved in aberrant proliferation, migration, and
      chemoresistance of tumor cells. It has been demonstrated that it can promote
      tumor growth by modulation multiple oncogenic signaling pathways. However, MTDH
      expression, significance, and related mechanism in chronic lymphocytic leukemia
      (CLL) are still unclear. The objective of this study was to investigate the
      expression of MTDH in CLL and the involvement of Wnt/beta-catenin signaling
      pathway in MTDH effects. Overexpression of MTDH mRNAs was seen in CLL samples.
      MTDH expression was associated with Rai stage classification of CLL, and altered
      levels of beta2-MG and lactate dehydrogenase in serum samples from patients.
      Overexpression of MTDH protein was seen in 87 % of CLL samples. Specific siRNAs
      inhibited MEC-1 cell growth and enhanced cell apoptosis (P < 0.05). Inhibition of
      MTDH expression resulted in decreased expression levels of lymphoid enhancer
      binding factor 1 (LEF-1), and its downstream target genes c-myc and cyclin D1.
      And there was a strong correlation between MTDH and LEF-1 protein expression in
      14 patients with CLL. The results demonstrate that MTDH is specifically expressed
      in B cell of CLL and exert a preservative role through activation of Wnt
      signaling pathway. Our findings indicated that MTDH may be a potential
      therapeutic target of CLL. 

PMID- 25575440
TI  - Clinical efficacy of preoperative chemotherapy with or without ifosfamide in
      patients with osteosarcoma of the extremity: meta-analysis of randomized
      controlled trials.
AB  - Ifosfamide has been used in neoadjuvant chemotherapy since the mid-1980s.
      Although several studies have been conducted, the results remain controversial.
      Randomized controlled trials have an improved balance of confounding factors and
      reliable results. Thus, we performed a meta-analysis based on randomized
      controlled trials to gather more evidence of the effect of ifosfamide on
      neoadjuvant chemotherapy for patients with osteosarcoma of the extremity. An
      electronic search was conducted via the Internet retrieval system to identify
      eligible trials until September 2014. Odds ratios (ORs) and 95 % confidence
      interval (CI) were calculated to compare the results of ifosfamide and ifosfamide
      free therapies. Four trials with a total of 1,378 patients were eligible for our
      meta-analysis. Overall, compared with neoadjuvant chemotherapy without
      ifosfamide, the use of ifosfamide had no advantage in terms of histological
      response to chemotherapy (cHR; OR 1.36; 95 % CI 0.90-2.03, P = 0.140), 5-year
      event-free survival (EFS; OR 1.16; 95 % CI 0.789-1.75, P = 0.464), and 5-year
      overall survival (OS; OR 1.06; 95 % CI 0.70-1.59, P = 0.794). However,
      improvement was noted in the rate of limb salvage (OR 4.06; 95 % CI 2.04-8.10, P
      < 0.001). Neoadjuvant chemotherapy with ifosfamide for patients with extremity
      osteosarcoma might not increase the cHR and exhibited no significant effect on
      either EFS or OS. However, ifosfamide therapy could significantly increase the
      rate of limb salvage for osteosarcoma of the extremity, which suggests that the
      preoperative use of ifosfamide could increase the success rate of limb salvage
      operation. 

PMID- 25575439
TI  - N-cadherin participated in invasion and metastasis of human esophageal squamous
      cell carcinoma via taking part in the formation of vasculogenic mimicry.
AB  - Vasculogenic mimicry (VM) refers to the unique ability of highly aggressive tumor
      cells to mimic the pattern of embryonic vasculogenic networks, and the presence
      of VM correlates to an increased risk of metastasis and poor clinical outcome of
      cancers. Several key molecules, including N-cadherin, have been implicated in VM.
      However, the role of N-cadherin in the formation of VM in esophageal squamous
      cell carcinoma (ESCC) had not been elucidated. In this study, firstly we aimed to
      identify VM patterns in ESCC tissues and to explore their clinical significance.
      VM was present in 12 out of 56 samples, and ESCC with lymph node metastasis had a
      higher incidence of VM than that without lymph node metastasis. More importantly,
      VM channels were associated with the expression of N-cadherin in ESCC tissues. In
      order to further explore the role of N-cadherin in VM formation and invasion and
      metastasis in ESCC, secondly, we silenced the expression of N-cadherin with small
      hairpin RNA in ESCC cell line KYSE-70; herein, we showed that KYSE-70 cells with
      N-cadherin silencing lost not only the capacity to form tube-like structures on
      collagen (VM) but also the invasion, metastasis and proliferation ability in KYSE
      70 cells in vitro. Taken together, antivascular therapies targeting tumor cell VM
      may be an effective approach to the treatment of patients with highly metastatic
      ESCC. 

PMID- 25575441
TI  - Scrub typhus caused by Orientia tsutsugamushi Kawasaki-related genotypes in
      Shandong Province, northern China.
AB  - Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate
      intracellular bacterium and characterized by dramatic genetic diversity. To
      elucidate the genotypes of O. tsutsugamushi populating in patients in Shandong
      Province, a new epidemic zone in China, we sequenced partial of the 56-kDa type
      specific antigen gene (TSA) and identified the genotypes of 43 O. tsutsugamushi
      samples from human patients confirmed with scrub typhus from 2010 to 2013. All of
      the 43 sequences are in the same clade, 39 of them are in one branch and the
      other four sequences, nominated as SH1002, SH1306, SH1309, and SH1307 are in four
      separate branches. To clarify the clinical characterizations caused by Kawasaki
      related genotypes, we studied the clinical profiles of these 43 scrub typhus
      patients. Most patients (88.1%) were farmers lived in rural areas. They presented
      with fever (100.0%), headache (79.1%), dizziness (32.6%), generalized myalgia
      (48.8%), fatigue (53.5%), anorexia (53.5%), facial flushing (23.3%), conjunctival
      congestion (11.6%), skin rashes (58.1%) and lymphadenopathy (23.3%). Eschar
      (97.7%) was quite common in patients, which provided doctors with a luminous clue
      for diagnosis of scrub typhus. Thrombocytopenia was seen in 23.1% of patients,
      and three patients (7.0%) had bronchopneumonia. There was no death report in
      Shandong Province during the study period. The present study provides beneficial
      data for clinical, serological, and molecular diagnosis of scrub typhus
      infections, and also provides foundations for subsequent studies. 

PMID- 25575442
TI  - Genetic variations in merozoite surface antigen genes of Babesia bovis detected
      in Vietnamese cattle and water buffaloes.
AB  - The genes that encode merozoite surface antigens (MSAs) in Babesia bovis are
      genetically diverse. In this study, we analyzed the genetic diversity of B. bovis
      MSA-1, MSA-2b, and MSA-2c genes in Vietnamese cattle and water buffaloes. Blood
      DNA samples from 258 cattle and 49 water buffaloes reared in the Thua Thien Hue
      province of Vietnam were screened with a B. bovis-specific diagnostic PCR assay.
      The B. bovis-positive DNA samples (23 cattle and 16 water buffaloes) were then
      subjected to PCR assays to amplify the MSA-1, MSA-2b, and MSA-2c genes.
      Sequencing analyses showed that the Vietnamese MSA-1 and MSA-2b sequences are
      genetically diverse, whereas MSA-2c is relatively conserved. The nucleotide
      identity values for these MSA gene sequences were similar in the cattle and water
      buffaloes. Consistent with the sequencing data, the Vietnamese MSA-1 and MSA-2b
      sequences were dispersed across several clades in the corresponding phylogenetic
      trees, whereas the MSA-2c sequences occurred in a single clade. Cattle- and water
      buffalo-derived sequences also often clustered together on the phylogenetic
      trees. The Vietnamese MSA-1, MSA-2b, and MSA-2c sequences were then screened for
      recombination with automated methods. Of the seven recombination events detected,
      five and two were associated with the MSA-2b and MSA-2c recombinant sequences,
      respectively, whereas no MSA-1 recombinants were detected among the sequences
      analyzed. Recombination between the sequences derived from cattle and water
      buffaloes was very common, and the resultant recombinant sequences were found in
      both host animals. These data indicate that the genetic diversity of the MSA
      sequences does not differ between cattle and water buffaloes in Vietnam. They
      also suggest that recombination between the B. bovis MSA sequences in both cattle
      and water buffaloes might contribute to the genetic variation in these genes in
      Vietnam. 

PMID- 25575443
TI  - A new era of improving progression-free survival with dual blockade in
      postmenopausal HR(+), HER2(-) advanced breast cancer.
AB  - Disease progression despite existing endocrine therapies remains a major
      challenge to the effective management of hormone-receptor-positive (HR(+)), human
      epidermal growth factor receptor-2-negative (HER2(-)), advanced breast cancer.
      Recent advances in elucidating the molecular mechanisms of disease progression
      have identified the existence of adaptive "cross-talk" between the estrogen
      receptor (ER) and various growth factor receptor and intracellular signaling
      pathways, allowing breast cancer cells to escape the inhibitory effects of
      endocrine therapy. These findings provide the clinical rationale for enhancing or
      extending endocrine sensitivity by combining endocrine therapy with a targeted
      agent against a compensatory pathway. In BOLERO-2, adding the mTOR inhibitor
      everolimus to endocrine therapy significantly improved progression-free survival
      (PFS) in patients with HR(+) advanced breast cancer previously treated with
      nonsteroidal aromatase inhibitor therapy. Notably, PFS benefits were comparable
      in subgroup analyses of first- and later-line settings. These results contrast
      with those of the large first-line HORIZON study, wherein adding the mTOR
      inhibitor temsirolimus to endocrine therapy did not improve PFS. Therefore, it is
      unclear whether a targeted agent should only be combined with endocrine therapy
      to restore endocrine sensitivity or whether it may also prevent or delay
      resistance in hormone-sensitive advanced breast cancer. Numerous additional
      targeted agents are currently being evaluated in combination with endocrine
      therapies, including PI3K, cyclin-dependent kinase 4/6, SRC, and histone
      deacetylase inhibitors. Appropriate patient selection based on prior treatment
      history will become increasingly important in maximizing the incremental benefit
      derived from these new agents combined with existing endocrine therapies in HR(+)
      advanced breast cancer. 

PMID- 25575444
TI  - A polygenic risk score for breast cancer in women receiving tamoxifen or
      raloxifene on NSABP P-1 and P-2.
AB  - Recent genetic studies have identified common variation in susceptibility loci
      that stratify lifetime risks of breast cancer and may inform prevention and
      screening strategies. However, whether these loci have similar implications for
      women treated with tamoxifen or raloxifene (SERMs) is unknown. We conducted a
      matched case-control study of 592 cases who developed breast cancer and 1,171
      unaffected women from 32,859 participants on SERM therapy enrolled on NSABP P-1
      and P-2 breast cancer prevention trials. We formed a quantitative polygenic risk
      score (PRS) using genotypes of 75 breast cancer-associated single nucleotide
      polymorphisms and examined the PRS as a risk factor for breast cancer among women
      treated with SERMs. The PRS ranged from 3.98 to 7.74, with a one-unit change
      associated with a 42 % increase in breast cancer (OR = 1.42; P = 0.0002). The PRS
      had a stronger association with breast cancer among high-risk women with no first
      degree family history (OR = 1.62) compared to those with a positive family
      history (OR = 1.32) (P intx = 0.04). There was also suggestion that PRS was a
      stronger risk factor for ER-positive (OR = 1.59, P = 0.0002) than ER-negative (OR
      = 1.05, P = 0.84) breast cancer (P intx = 0.10). Associations did not differ by
      tamoxifen or raloxifene treatment, age at trial entry, 5-year predicted Gail
      model risk or other clinical variables. The PRS is a strong risk factor for ER
      positive breast cancer in moderate to high-risk individuals treated with either
      tamoxifen or raloxifene for cancer prevention. These data suggest that common
      genetic variation informs risk of breast cancer in women receiving SERMs.

PMID- 25575445
TI  - Mutation screening of PALB2 in clinically ascertained families from the Breast
      Cancer Family Registry.
AB  - Loss-of-function mutations in PALB2 are associated with an increased risk of
      breast cancer, with recent data showing that female breast cancer risks for PALB2
      mutation carriers are comparable in magnitude to those for BRCA2 mutation
      carriers. This study applied targeted massively parallel sequencing to
      characterize the mutation spectrum of PALB2 in probands attending breast cancer
      genetics clinics in the USA. The coding regions and proximal intron-exon
      junctions of PALB2 were screened in probands not known to carry a mutation in
      BRCA1 or BCRA2 from 1,250 families enrolled through familial cancer clinics by
      the Breast Cancer Family Registry. Mutation screening was performed using Hi
      Plex, an amplicon-based targeted massively parallel sequencing platform.
      Screening of PALB2 was successful in 1,240/1,250 probands and identified nine
      women with protein-truncating mutations (three nonsense mutations and five
      frameshift mutations). Four of the 33 missense variants were predicted to be
      deleterious to protein function by in silico analysis using two different
      programs. Analysis of tumors from carriers of truncating mutations revealed that
      the majority were high histological grade, invasive ductal carcinomas. Young
      onset was apparent in most families, with 19 breast cancers under 50 years of
      age, including eight under the age of 40 years. Our data demonstrate the utility
      of Hi-Plex in the context of high-throughput testing for rare genetic mutations
      and provide additional timely information about the nature and prevalence of
      PALB2 mutations, to enhance risk assessment and risk management of women at high
      risk of cancer attending clinical genetic services.

PMID- 25575446
TI  - Luminal progenitor and fetal mammary stem cell expression features predict breast
      tumor response to neoadjuvant chemotherapy.
AB  - Mammary gland morphology and physiology are supported by an underlying cellular
      differentiation hierarchy. Molecular features associated with particular cell
      types along this hierarchy may contribute to the biological and clinical
      heterogeneity observed in human breast carcinomas. Investigating the normal
      cellular developmental phenotypes in breast tumors may provide new prognostic
      paradigms, identify new targetable pathways, and explain breast cancer subtype
      etiology. We used transcriptomic profiles coming from fluorescence-activated cell
      sorted (FACS) normal mammary epithelial cell types from several independent human
      and murine studies. Using a meta-analysis approach, we derived consensus gene
      signatures for both species and used these to relate tumors to normal mammary
      epithelial cell phenotypes. We then compiled a dataset of breast cancer patients
      treated with neoadjuvant anthracycline and taxane chemotherapy regimens to
      determine if normal cellular traits predict the likelihood of a pathological
      complete response (pCR) in a multivariate logistic regression analysis with
      clinical markers and genomic features such as cell proliferation. Most human and
      murine tumor subtypes shared some, but not all, features with a specific FACS
      purified normal cell type; thus for most tumors a potential distinct cell type of
      'origin' could be assigned. We found that both human luminal progenitor and mouse
      fetal mammary stem cell features predicted pCR sensitivity across all breast
      cancer patients even after controlling for intrinsic subtype, proliferation, and
      clinical variables. This work identifies new clinically relevant gene signatures
      and highlights the value of a developmental biology perspective for uncovering
      relationships between tumor subtypes and their potential normal cellular
      counterparts. 

PMID- 25575448
TI  - Gamma oscillations in visual cortex: the stimulus matters.

PMID- 25575447
TI  - Effects of dietary selenium on host response to necrotic enteritis in young
      broilers.
AB  - The effects of dietary supplementation of young broiler chickens with an organic
      selenium (Se) formulation, B-Traxim Se, on experimental necrotic enteritis (NE)
      were studied. Chickens treated with three Se doses (0.25, 0.50, 1.00 mg/kg) from
      hatch were orally challenged with Eimeria maxima at 14 days of age followed by
      Clostridium perfringens to induce NE. Chickens fed with 0.50 mg/kg Se showed
      significantly increased body weights and antibody levels against NetB, and
      significantly reduced gut lesions compared with non-supplemented chickens.
      However, there were no significant differences in Eimeria oocyst shedding between
      the Se-treated and non-supplemented groups. Levels of IL-1beta, IL-6, IL-8, iNOS,
      LITAF, TNFSF15, AvBD6, AvBD8, and AvBD13 transcripts were increased in the gut
      and spleen of at least one of the three Se-treated groups compared with the non
      treated group. These results suggest that dietary supplementation of young
      broilers with Se might be beneficial to reduce the negative consequence of NE. 

PMID- 25575449
TI  - Spatial imagery relies on a sensory independent, though sensory sensitive,
      functional organization within the parietal cortex: a fMRI study of angle
      discrimination in sighted and congenitally blind individuals.
AB  - Although vision offers distinctive information to space representation,
      individuals who lack vision since birth often show perceptual and
      representational skills comparable to those found in sighted individuals.
      However, congenitally blind individuals may result in impaired spatial analysis,
      when engaging in 'visual' spatial features (e.g., perspective or angle
      representation) or complex spatial mental abilities. In the present study, we
      measured behavioral and brain responses using functional magnetic resonance
      imaging in sighted and congenitally blind individuals during spatial imagery
      based on a modified version of the mental clock task (e.g., angle discrimination)
      and a simple recognition control condition, as conveyed across distinct sensory
      modalities: visual (sighted individuals only), tactile and auditory. Blind
      individuals were significantly less accurate during the auditory task, but
      comparable-to-sighted during the tactile task. As expected, both groups showed
      common neural activations in intraparietal and superior parietal regions across
      visual and non-visual spatial perception and imagery conditions, indicating the
      more abstract, sensory independent functional organization of these cortical
      areas, a property that we named supramodality. At the same time, however,
      comparisons in brain responses and functional connectivity patterns across
      experimental conditions demonstrated also a functional lateralization, in a way
      that correlated with the distinct behavioral performance in blind and sighted
      individuals. Specifically, blind individuals relied more on right parietal
      regions, mainly in the tactile and less in the auditory spatial processing. In
      sighted, spatial representation across modalities relied more on left parietal
      regions. In conclusions, intraparietal and superior parietal regions subserve
      supramodal spatial representations in sighted and congenitally blind individuals.
      Differences in their recruitment across non-visual spatial processing in sighted
      and blind individuals may be related to distinctive behavioral performance and/or
      mental strategies adopted when they deal with the same spatial representation as
      conveyed through different sensory modalities. 

PMID- 25575451
TI  - Right hemisphere or valence hypothesis, or both? The processing of hybrid faces
      in the intact and callosotomized brain.
AB  - The valence hypothesis and the right hemisphere hypothesis in emotion processing
      have been alternatively supported. To better disentangle the two accounts, we
      carried out two studies, presenting healthy participants and an anterior
      callosotomized patient with 'hybrid faces', stimuli created by superimposing the
      low spatial frequencies of an emotional face to the high spatial frequencies of
      the same face in a neutral expression. In both studies we asked participants to
      judge the friendliness level of stimuli, which is an indirect measure of the
      processing of emotional information, despite this remaining "invisible". In
      Experiment 1 we presented hybrid faces in a divided visual field paradigm using
      different tachistoscopic presentation times; in Experiment 2 we presented hybrid
      chimeric faces in canonical view and upside-down. In Experiments 3 and 4 we
      tested a callosotomized patient, with spared splenium, in similar paradigms as
      those used in Experiments 1 and 2. Results from Experiments 1 and 3 were
      consistent with the valence hypothesis, whereas results of Experiments 2 and 4
      were consistent with the right hemisphere hypothesis. This study confirms that
      the low spatial frequencies of emotional faces influence the social judgments of
      observers, even when seen for 28 ms (Experiment 1), possibly by means of
      configural analysis (Experiment 2). The possible roles of the cortical and
      subcortical emotional routes in these tasks are discussed in the light of the
      results obtained in the callosotomized patient. We propose that the right
      hemisphere and the valence accounts are not mutually exclusive, at least in the
      case of subliminal emotion processing.

PMID- 25575452
TI  - Ill-defined problem solving in amnestic mild cognitive impairment: linking
      episodic memory to effective solution generation.
AB  - It is well accepted that the medial temporal lobes (MTL), and the hippocampus
      specifically, support episodic memory processes. Emerging evidence suggests that
      these processes also support the ability to effectively solve ill-defined
      problems which are those that do not have a set routine or solution. To test the
      relation between episodic memory and problem solving, we examined the ability of
      individuals with single domain amnestic mild cognitive impairment (aMCI), a
      condition characterized by episodic memory impairment, to solve ill-defined
      social problems. Participants with aMCI and age and education matched controls
      were given a battery of tests that included standardized neuropsychological
      measures, the Autobiographical Interview (Levine et al., 2002) that scored for
      episodic content in descriptions of past personal events, and a measure of ill
      defined social problem solving. Corroborating previous findings, the aMCI group
      generated less episodically rich narratives when describing past events.
      Individuals with aMCI also generated less effective solutions when solving ill
      defined problems compared to the control participants. Correlation analyses
      demonstrated that the ability to recall episodic elements from autobiographical
      memories was positively related to the ability to effectively solve ill-defined
      problems. The ability to solve these ill-defined problems was related to measures
      of activities of daily living. In conjunction with previous reports, the results
      of the present study point to a new functional role of episodic memory in ill
      defined goal-directed behavior and other non-memory tasks that require flexible
      thinking. Our findings also have implications for the cognitive and behavioural
      profile of aMCI by suggesting that the ability to effectively solve ill-defined
      problems is related to sustained functional independence. 

PMID- 25575450
TI  - Role of inter-hemispheric transfer in generating visual evoked potentials in V1
      damaged brain hemispheres.
AB  - Partial cortical blindness is a visual deficit caused by unilateral damage to the
      primary visual cortex, a condition previously considered beyond hopes of
      rehabilitation. However, recent data demonstrate that patients may recover both
      simple and global motion discrimination following intensive training in their
      blind field. The present experiments characterized motion-induced neural activity
      of cortically blind (CB) subjects prior to the onset of visual rehabilitation.
      This was done to provide information about visual processing capabilities
      available to mediate training-induced visual improvements. Visual Evoked
      Potentials (VEPs) were recorded from two experimental groups consisting of 9 CB
      subjects and 9 age-matched, visually-intact controls. VEPs were collected
      following lateralized stimulus presentation to each of the 4 visual field
      quadrants. VEP waveforms were examined for both stimulus-onset (SO) and motion
      onset (MO) related components in postero-lateral electrodes. While stimulus
      presentation to intact regions of the visual field elicited normal SO-P1, SO-N1,
      SO-P2 and MO-N2 amplitudes and latencies in contralateral brain regions of CB
      subjects, these components were not observed contralateral to stimulus
      presentation in blind quadrants of the visual field. In damaged brain
      hemispheres, SO-VEPs were only recorded following stimulus presentation to intact
      visual field quadrants, via inter-hemispheric transfer. MO-VEPs were only
      recorded from damaged left brain hemispheres, possibly reflecting a native
      left/right asymmetry in inter-hemispheric connections. The present findings
      suggest that damaged brain hemispheres contain areas capable of responding to
      visual stimulation. However, in the absence of training or rehabilitation, these
      areas only generate detectable VEPs in response to stimulation of the intact
      hemifield of vision. 

PMID- 25575453
TI  - Adult exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with
      disruption of the hypothalamic-pituitary-testicular axis.
AB  - Reproductive physiology involves complex biological processes that can be
      disrupted by exposure to environmental contaminants. The effects of bisphenol A
      (BPA) on spermatogenesis and sperm quality is still unclear. The objective of
      this study was to investigate the reproductive toxicity of BPA at dosages
      considered to be safe (5 or 25mg BPA/kg/day). We assessed multiple sperm
      parameters, the relative expression of genes involved in the central regulation
      of the hypothalamic-pituitary-testicular axis, and the serum concentrations of
      testosterone, estradiol, LH and FSH. BPA exposure reduced sperm production,
      reserves and transit time. Significant damage to the acrosomes and the plasma
      membrane with reduced mitochondrial activity and increased levels of defective
      spermatozoa may have compromised sperm function and caused faster movement
      through the epididymis. BPA exposure reduced the serum concentrations of
      testosterone, LH and FSH and increased the concentration of estradiol. The
      relative gene expression revealed an increase in gonadotropin releasing hormone
      receptor (Gnrhr), luteinizing hormone beta (Lhb), follicle stimulating hormone
      beta (Fshb), estrogen receptor beta (Esr2) and androgen receptor (Ar) transcripts
      in the pituitary and a reduction in estrogen receptor alpha (Esr1) transcripts in
      the hypothalamus. In this study, we demonstrated for the first time that adult
      male exposure to BPA caused a reduction in sperm production and specific
      functional parameters. The corresponding pattern of gene expression is indicative
      of an attempt by the pituitary to reestablish normal levels of LH, FSH and
      testosterone serum concentrations. In conclusion, these data suggest that at
      dosages previously considered nontoxic to reproductive function, BPA compromises
      the spermatozoa and disrupts the hypothalamic-pituitary-gonadal axis, causing a
      state of hypogonadotropic hypogonadism. 

PMID- 25575454
TI  - Clinical research and medical care: towards effective and complete integration.
AB  - BACKGROUND: Despite their close relationship, clinical research and medical care
      have become separated by clear boundaries. The purpose of clinical research is to
      generate generalizable knowledge useful for future patients, whereas medical care
      aims to promote the well-being of individual patients. The evolution towards
      patient-centered medicine and patient-oriented research, and the gradual
      standardization of medicine are contributing to closer ties between clinical
      research and medical practice. But the integration of both activities requires
      addressing important ethical and methodological challenges. DISCUSSION: From an
      ethical perspective, clinical research should evolve from a position of
      paternalistic beneficence to a situation in which the principle of non
      maleficence and patient autonomy predominate. The progressive adoption of
      "patient-oriented informed consent", "patient equipoise", and "altruism-based
      research", and the application of risk-based ethical oversight, in which the
      level of regulatory scrutiny is adapted to the potential risk for patients, are
      crucial steps to achieve the integration between research and care. From a
      methodological standpoint, careful and systematic observations should have
      greater relevance in clinical research, and experiments should be embedded into
      usual clinical practice. Clinical research should focus on individuals through
      the development of patient-oriented research. In a complementary way, the
      integration of experiments into medical practice through the systematic
      application of "point of care research" could help to generate knowledge for the
      individuals and for the populations. SUMMARY: The integration of clinical
      research and medical care will require researchers, clinicians, health care
      managers, and patients to reevaluate the way they understand both activities. The
      development of an integrated learning health care system will contribute to
      generating and applying clinically relevant medical knowledge, producing benefits
      for present and future patients.

PMID- 25575455
TI  - Adrenomedullary progenitor cells: Isolation and characterization of a multi
      potent progenitor cell population.
AB  - The adrenal is a highly plastic organ with the ability to adjust to physiological
      needs by adapting hormone production but also by generating and regenerating both
      adrenocortical and adrenomedullary tissue. It is now apparent that many adult
      tissues maintain stem and progenitor cells that contribute to their maintenance
      and adaptation. Research from the last years has proven the existence of stem and
      progenitor cells also in the adult adrenal medulla throughout life. These cells
      maintain some neural crest properties and have the potential to differentiate to
      the endocrine and neural lineages. In this article, we discuss the evidence for
      the existence of adrenomedullary multi potent progenitor cells, their isolation
      and characterization, their differentiation potential as well as their clinical
      potential in transplantation therapies but also in pathophysiology. 

PMID- 25575456
TI  - Effect of liraglutide on proliferation and differentiation of human adipose stem
      cells.
AB  - Glucagon-Like Peptide-1 (GLP-1) receptor agonists, used as glucose-lowering
      drugs, also induce weight loss by inhibiting food intake. The present study was
      aimed at the assessment of the in vitro effects of the GLP-1 receptor agonist
      liraglutide on proliferation and differentiation of human adipose stem cells
      (ASC) obtained from subcutaneous adipose tissue of morbidly obese subjects
      undergoing bariatric surgery. Liraglutide (10-100 nM) significantly inhibited ASC
      proliferation and viability, with a maximum effect at 6 days of culture (45% and
      50%, for liraglutide 10 and 100 nM, respectively); the effect was reverted by
      exendin 9-39. Glucose uptake was significantly reduced by liraglutide in a dose
      dependent manner. Treatment with liraglutide reduced intracellular lipid
      accumulation in differentiating ASC, together with FABP-4 mRNA expression (-18%, 
      23%, -46%, for 1 nM, 10 nM and 100 nM, respectively), whereas it stimulated
      adiponectin (APN) expression (1.86-, 2.64-, 2.28-fold increase, for 1 nM, 10 nM
      and 100 nM, respectively). Liraglutide exerts effects on human adipose cell
      precursors, inhibiting proliferation and differentiation, while stimulating the
      expression of the insulin-sensitizing adipokine APN. These effects could
      contribute to the actions of GLP-1 receptor agonists on body weight and insulin
      sensitivity. 

PMID- 25575457
TI  - Flatfish metamorphosis: a hypothalamic independent process?
AB  - Anuran and flatfish metamorphosis are tightly regulated by thyroid hormones that
      are the necessary and sufficient factors that drive this developmental event. In
      the present study whole mount in situ hybridization (WISH) and quantitative PCR
      in sole are used to explore the central regulation of flatfish metamorphosis.
      Central regulation of the thyroid in vertebrates is mediated by the hypothalamus
      pituitary-thyroid (HPT) axis. Teleosts diverge from other vertebrates as
      hypothalamic regulation in the HPT axis is proposed to be through hypothalamic
      inhibition although the regulatory factor remains enigmatic. The dynamics of the
      HPT axis during sole metamorphosis revealed integration between the activity of
      the thyrotrophes in the pituitary and the thyroid follicles. No evidence was
      found supporting a role for thyroid releasing hormone (trh) or corticotrophin
      releasing hormone (crh) in hypothalamic control of TH production during sole
      metamorphosis. Intriguingly the results of the present study suggest that neither
      hypothalamic trh nor crh expression changes during sole metamorphosis and raises
      questions about the role of these factors and the hypothalamus in regulation of
      thyrotrophs. 

PMID- 25575459
TI  - Patients recovering from abdominal surgery who walked with volunteers exhibited
      improved postoperative recovery profiles during hospitalization: reply.

PMID- 25575460
TI  - Diagnostic evaluation of achalasia: from the whalebone to the Chicago
      classification.
AB  - From the earliest description of dysphagia relieved by dilatation with a
      whalebone in 1674 we have witnessed the evolution of esophageal function testing
      from the conventional manometry to the high-resolution manometry (HRM) and
      esophageal topography pressure plotting that have led to the revised Chicago
      classification for esophageal motility disorders in 2014. The goals of this paper
      are, therefore, (1) to highlight the historical milestones that have led to the
      diagnostic definition of achalasia, as we know it today; (2) to describe the
      evaluation process of patients with suspected achalasia; (3) to describe the
      diagnostic value of the HRM and the usefulness of the Chicago classification in
      predicting treatment outcomes. The value of Chicago classification is linked to
      the ability of the clinician to perform a thorough clinical evaluation to
      identify and correlate specific clinical phenotypes to specific manometric
      subtypes and predict treatment outcomes. Chicago classification, however, cannot
      predict which treatment, pneumatic dilatation, or Heller myotomy, should be
      selected for those with a specific subtype of achalasia. 

PMID- 25575458
TI  - Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early
      stage breast cancer.
AB  - PURPOSE: Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss.
      Receptor Activator of Nuclear Factor Kappa-B (RANK)-RANK ligand (RANK-L)
      signaling balances bone resorption and formation. Osteoprotegerin (OPG) acts as a
      decoy receptor for RANK, interrupting osteoclast activation and bone resorption.
      This study examined the relationship between OPG and bone loss in women with
      CIOF. METHODS: Premenopausal women with stage I/II breast cancers receiving
      adjuvant chemotherapy were evaluated at chemotherapy initiation, 6 and 12 months.
      Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN),
      follicle stimulating hormone (FSH), ionized calcium, osteocalcin, and OPG were
      serially measured. CIOF was defined as a negative pregnancy test, FSH levels >30
      MIU/mL, and >=3 months of amenorrhea. RESULTS: Forty women were enrolled; 31
      (77.5%) met CIOF criteria. BMD significantly decreased (p < 0.001) in the CIOF
      group at both time points: LS BMD decreased from a median of 0.993 g/cm(2) to
      0.976 g/cm(2) and 0.937 g/cm(2) at 6 and 12 months, respectively. OPG was
      significantly elevated at 6 months (median increase 0.30 pmol/L, p = 0.015) and
      then decreased at 12 months to levels still above baseline (median difference 0.2
      pmol/L, p = 0.70). CONCLUSIONS: In what was likely a compensatory response to
      rapid bone loss, CIOF patients' OPG levels increased at 6 months and then
      decreased at 12 months to values greater than baseline assessments. This
      phenomenon is described in other diseases, but never before in CIOF.

PMID- 25575461
TI  - Crohn's disease-specific anti-CUZD1 pancreatic antibodies are absent in ruminants
      with paratuberculosis.
AB  - BACKGROUND: Pancreatic autoantibodies (PABs) specifically recognizing GP2 and/or
      CUZD1 are present in more than 35% of patients with Crohn's disease (CrD). We
      have recently provided evidence of the presence of GP2-specific PABs in ruminants
      with paratuberculosis (ptb), a Mycobacterium avium paratuberculosis (MAP)-induced
      disease resembling CrD. OBJECTIVE: To assess whether anti-CUZD1 antibodies are
      also present in ruminants with ptb. METHODS: A total of 110 samples (73 cattle/37
      sheep) were studied including 40 with ptb (24 cattle/16 sheep; 20 anti-GP2
      antibody pos) and 70 without ptb (49 cattle/21 sheep; 10 anti-GP2 antibody pos).
      The samples were pre-characterized for anti-MAP and anti-GP2 antibodies by ELISA.
      Evidence of MAP was confirmed by PCR. Anti-CUZD1 antibody testing was performed
      by indirect immunofluorescence (IIF) based on transfected HEK293 cells expressing
      CUZD1. Anti-sheep or anti-cattle specific antisera were used as revealing
      antibodies. RESULTS: None of the ruminant sera had anti-CUZD1 antibodies by IIF
      testing at dilutions varying from 1/10 to 1/160. Methodological flaws were
      prevented by a series of tests. Control sera from anti-CUZD1 positive CrD samples
      have shown anti-CUZD1 antibody reactivity at various concentrations. Antibody
      reactivity to GP2-expressing HEK293 cells has confirmed the reactivity to GP2 in
      ruminant sera found positive for anti-GP2 antibodies by ELISA. CONCLUSION: The
      present study has found no evidence of anti-CUZD1 PABs in MAP-induced ptb. Our
      findings indicate that the induction of CUZD1-specific PABs is unrelated to MAP
      infection and that the mechanisms responsible for the loss of tolerance to GP2
      and CUZD1 are probably quite distinct.

PMID- 25575462
TI  - Expression, purification, crystallization, and preliminary X-ray crystallographic
      studies of the human adiponectin receptors, AdipoR1 and AdipoR2.
AB  - The adiponectin receptors (AdipoR1 and AdipoR2) are membrane proteins with seven
      transmembrane helices. These receptors regulate glucose and fatty acid
      metabolism, thereby ameliorating type 2 diabetes. The full-length human AdipoR1
      and a series of N-terminally truncated mutants of human AdipoR1 and AdipoR2 were
      expressed in insect cells. In small-scale size exclusion chromatography, the
      truncated mutants AdipoR1Delta88 (residues 89-375) and AdipoR2Delta99 (residues
      100-386) eluted mostly in the intact monodisperse state, while the others eluted
      primarily as aggregates. However, gel filtration chromatography of the large
      scale preparation of the tag-affinity-purified AdipoR1Delta88 revealed the
      presence of an excessive amount of the aggregated state over the intact state.
      Since aggregation due to contaminating nucleic acids may have occurred during the
      sample concentration step, anion-exchange column chromatography was performed
      immediately after affinity chromatography, to separate the intact AdipoR1Delta88
      from the aggregating species. The separated intact AdipoR1Delta88 did not undergo
      further aggregation, and was successfully purified to homogeneity by gel
      filtration chromatography. The purified AdipoR1Delta88 and AdipoR2Delta99
      proteins were characterized by thermostability assays with 7-diethylamino-3-(4
      maleimidophenyl)-4-methyl coumarin, thin layer chromatography of bound lipids,
      and surface plasmon resonance analysis of ligand binding, demonstrating their
      structural integrities. The AdipoR1Delta88 and AdipoR2Delta99 proteins were
      crystallized with the anti-AdipoR1 monoclonal antibody Fv fragment, by the
      lipidic mesophase method. X-ray diffraction data sets were obtained at
      resolutions of 2.8 and 2.4 A, respectively. 

PMID- 25575464
TI  - Pancreatic involvement in Legionella pneumonia.
AB  - Legionella-associated pancreatitis has been rarely reported. Since this condition
      is very rarely suspected and investigated in patients with Legionella pneumonia,
      its incidence is probably underestimated. Here we report a case of Legionella
      pneumonia-associated pancreatitis and review the relevant related literature. 

PMID- 25575463
TI  - Infective endocarditis on ICU: risk factors, outcome and long-term follow-up.
AB  - OBJECTIVE: To identify factors associated with short-term, intermediate and long
      term outcome in patients with infective endocarditis (IE) and the need for
      treatment on intensive care unit (ICU). DESIGN AND SETTING: Retrospective
      analysis and long-term follow-up by questionnaire in the two medical ICUs of our
      university hospital. PATIENTS: We conducted a retrospective analysis of all
      consecutive patients with IE and need for ICU treatment in our department between
      2002 and 2009. All patients fulfilled the modified Duke criteria for definite
      diagnosis of IE. MEASUREMENTS AND MAIN RESULTS: Data of 216 patients (aged 62 +/-
      14 years, 31 % female) were analyzed, 15.7 % of whom had prosthetic valve
      endocarditis. Infectious agent (IA) was identified in 74 % and surgery was
      performed in 57 %. 56 patients (24.9 %) died on ICU, 9 patients were sent to
      palliative care units and died several days later. During follow-up, another 44
      patients died. Multivariate Cox-regression analysis identified the following
      independent risk factors: High initial SAPS II for 30d-, multiple organ failure
      and high maximum SAPS II for 100d- and high maximum leukocyte count for long-term
      mortality. Surgical intervention during ICU was an independent predictor of a
      better 30d outcome. CONCLUSIONS: In contrast to general IE populations, IA and
      the type of infected impaired valve are not main predictors of survival in
      critically ill IE-patients. Biomarker of acute infection and markers for severity
      of illness (scores and organ failure) are independent risk factors for mortality.
      The surgical clearance of infected valve, device or abscesses is an independent
      predictor of 30d outcome.

PMID- 25575465
TI  - Environmentally-defined enhancer populations regulate diversity of tissue
      resident macrophages.
AB  - Macrophages represent a class of cells specialized for phagocytosis that occurs
      in multiple, phenotypically distinct populations throughout the body. Two studies
      published in Cell demonstrate that these phenotypic differences reflect drastic
      differences in the populations of enhancers that regulate transcription, and that
      this epigenomic diversity is, in fact, highly plastic and sensitive to
      environmental cues. 

PMID- 25575466
TI  - Good food and bad: Nutritional and pleasurable eating in ancient Greece.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This paper speaks to the theme of the boundaries
      of food and medicine as constructed in the Greek and Roman worlds. It examines
      how physicians developed innovative ways of thinking about the body that did not
      attribute health and sickness to the intervention of gods. Ancient physicians and
      natural historians conceived of new potencies for substances and described their
      impact on the body's physiology between the late fifth century BC and the early
      third century AD. The legacy of these ideas and practices had great traction in
      the Mediterranean world and survived into Early Modern Times, and until the rise
      of new forms of science. MATERIALS AND METHODS: This article analyses texts
      transmitted from the ancient world and considers how substances were attributed
      nutritional and medical potency. The texts relevant to this analysis include
      medical and philosophical treatises as well as cookery books. The article
      highlights discussions about the nature of food and drugs and the herbs thought
      to cross the boundaries between them. It interrogates different contexts within
      which foods were thought good or bad for the body, and the social and moral
      connotations attached to those perceptions. CONCLUSION: Much of the analysis is
      devoted to understanding the flavours that were a key marker in the nutritional
      potencies attributed to foodstuffs. However there are clear and influential moral
      boundaries set by Plato in the discourse around food and pleasure. While every
      physician should be a chef, and many wrote cookery books that have been lost, a
      chef's talent was located in increasing pleasure, and therefore a less valuable
      skill. However the different literary genres show overlapping terminology and
      concerns, particularly with the quality of ingredients. Poor taste was not only a
      culinary concern. With regard to the setting of boundaries between foods and
      medicines, the transition between one category and another is frequently
      determined by the preparation and strengthening of a food's potency.

PMID- 25575467
TI  - Antidiarrhoeal activity of aqueous extract of Mangifera indica L. leaves in
      female albino rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Mangifera indica L. leaves have a long history of
      indigenous use, as an antidiarrhoeal agent among others, without any scientific
      study that has substantiated or refuted this claim. Therefore, the aims of this
      study were to determine the secondary metabolites in the aqueous extract of
      Mangifera indica leaves and its acclaimed antidiarrhoeal activity in rats.
      MATERIALS AND METHODS: The aqueous leaf extract of Mangifera indica was screened
      for its constituent secondary plant metabolites. In each of the diarrhoeal
      models, female albino rats were assigned into 5 groups (A, B, C, D and E)
      containing five animals each such that rats in groups A and B were the positive
      and negative controls respectively while those in groups C, D and E received 25,
      50 and 100mg/kg body weight of the extract respectively in addition to specific
      requirements of the model. RESULTS: The extract contained alkaloids (4.20mg/g),
      flavonoids (13.60mg/g), phenolics (1.50mg/g) and saponins (3.10mg/g) while
      tannins, anthraquinones, cardiac glycosides and steroids were not detected. In
      the castor oil-induced diarrhoeal model, the onset time of diarrhoea was
      significantly prolonged by the 25 and 50mg/kg body weight whereas there was no
      episode in the 100mg/kg body weight treated animals. The extract (25 and 50mg/kg
      body weight) decreased the number, water content, fresh weight and total number
      of wet feaces and increased the inhibition of defecations. All the doses of the
      extract significantly increased the Na(+) -K(+) ATPase activity in the small
      intestine. The extract dose dependently decreased the masses and volume of
      intestinal fluid with corresponding increase in inhibition of intestinal fluid
      content in the castor oil-induced enteropooling model. The extract also reduced
      the distance travelled by charcoal meal in the 30min gastrointestinal transit
      model. All these changes were similar to the reference drugs with the 100mg/kg
      body weight of the extract exhibiting the most profound antidiarrhoeal activity.
      CONCLUSION: The study concluded that the aqueous extract of Mangifera indica
      leaves possess antidiarrhoeal activity in chemical induced diarrhoeal models and
      thus justifies its age long folkloric use in managing diarrhoea. The presence of
      alkaloids, flavonoids, phenolics, saponins and enhancement of Na(+) -K(+) ATPase
      activity might play roles in the antidiarrhoeal activity of the plant extract.

PMID- 25575468
TI  - Eucommia ulmoides Oliv. bark aqueous extract inhibits osteoarthritis in a rat
      model of osteoarthritis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. bark (EU) is a common
      traditional Chinese herbal medicine for treatment of osteoarthritis (OA), but its
      therapeutic effect on OA and the underlying mechanisms have not been fully
      clarified. Our previous study showed that Eucommia ulmoides Oliv. bark aqueous
      extract (EUE) had a protective effect on cartilage, and this study was aimed to
      investigate the anti-osteoarthritis effect and mechanisms of EUE in a rat model
      of osteoarthritis. MATERIALS AND METHODS: Thirty-two 5-week-old specific pathogen
      free Sprague-Dawley rats which were randomized into four even groups (n=8). Group
      A received sham operation while the OA model was established using the modified
      Hulth technique in groups B, C and D. For eight weeks after operation, in
      addition to routine feeding, group A received gavage with deionized water, group
      B with deionized water, group C with 1.35 g/kg/day EUE, and group D with 2.7
      g/kg/day EUE. Eight weeks postoperatively, all of the animals were euthanized for
      radiological, gross and histopathological observations to evaluate the effect of
      EUE on OA and to determine its potential mechanisms. RESULTS: Radiological and
      histopathological observations showed that the articular degenerative changes
      were significantly more alleviated in groups C and D than in group B, while there
      were no obviously degenerative manifestations in group A. Mankin's scores in
      groups C and D were significantly lower than in group B (P<0.01). The severity of
      OA was significantly less in group D than in group C (P<0.01). The IL-1beta and
      IL-6 contents in serum and MMP-3 secretion in articular cartilage were
      significantly lower in groups C and D than those in group B (P<0.01), and
      significantly lower in group D than those in group C (P<0.01). Compared with
      group B, phosphorylated Akt was significantly down-regulated in groups C and D.
      CONCLUSIONS: EUE may inhibit the progression of osteoarthritis by inhibiting the
      PI3K/Akt pathway to delay cartilage degeneration, reduce inflammatory cytokines
      and prevent MMP-3 secretion. Therefore, EU is a potential therapeutic agent for
      OA, but its efficacy is limited.

PMID- 25575469
TI  - Antiresorptive therapy in the management of cancer treatment-induced bone loss.
AB  - Cancer treatment-induced bone loss treatment has an important role to prevent
      bone loss-related events like fracture, significant morbidity, mortality,
      disfigurement and loss of self-esteem, and health-care expenditure. Numerous
      factors, including treatment regimens and bone metastasis, increase the risk of
      osteoporosis or local bone destruction in most breast and prostate cancer
      patients. Cytotoxic chemotherapies, radiation, and hormonal therapies can lead to
      premature menopause and decrease bone mineral density. Over 60 % of breast cancer
      patients within 1 year of beginning postoperative adjuvant chemotherapy
      experience ovarian failure. Also, ovarian ablation and aromatase inhibitors used
      to treat breast cancer and orchiectomy and androgen deprivation therapy (ADT; to
      treat prostate cancer) cause substantial bone loss. In this article, we will
      focus mainly on antiresorptive therapy in the management of cancer treatment
      induced bone loss (CTIBL). An understanding of CTIBL is critical for determining
      how to assess the risk and identify which patients may benefit from preventive
      therapy. 

PMID- 25575470
TI  - [Hip fracture prosthetics in German trauma surgery. State of the art].
AB  - BACKGROUND: To improve patient safety and quality in joint arthroplasty a
      certification of arthroplasty centers (EndoCert(c)) and a German arthroplasty
      register (EPRD) have been implemented. This should guarantee a long-term
      improvement in documentation of arthroplasty in the future. Although the stages
      of operations in elective and trauma-associated joint arthroplasty are
      comparable, the surgical preconditions are often quite different. As required by
      the German Society of Trauma Surgery (DGU) this study analyzed the current
      situation with respect to the proportion of fracture-associated joint
      arthroplasties among the total volume carried out in Germany. MATERIAL AND
      METHODS: A uniform internet-based questionnaire was sent to all listed trauma
      centers in Germany by the central office of the DGU. In addition any information
      regarding hip joint arthroplasty in 2011 was collected from the Federal
      Statistical Office of Germany. RESULTS: The questionnaire was returned by 324 (47
      %) out of 690 of the trauma centers contacted. A total of 34,135 total hip
      arthroplasties (THA) and 26,753 total knee arthroplasties (TKA) were carried out
      in 2011 by these clinics. The absolute numbers for total endoprosthesis
      replacement cited by the trauma centers were 5718 THAs and 3829 TKAs. According
      to the data from the Federal Statistical Office of Germany 131,966 hip fractures
      were registered in 2011, including 69,582 femoral neck fractures (patient age >19
      years) and 62,384 pertrochanteric fractures. From a total number of THAs of
      approximately 200,000 in Germany 47,695 (approximately 25 %) of these were
      associated with trauma. DISCUSSION: The data analyzed in this study and the
      results obtained from known literature sources demonstrate that THA is the most
      frequently performed procedure in trauma management of femoral neck fractures.
      Because of the ubiquitous and high incidence and the need for emergency treatment
      due to correlated risks and complications of delayed treatment, a high and
      standardized around the clock (24 h and 7 days a week) treatment option is
      mandatory. Long waiting times to treatment or transfer are inacceptable due to
      the increased mortality and complications.

PMID- 25575471
TI  - The application of tribology in assessing texture perception of oral liquid
      medicines.
AB  - The palatability of medicines is likely to have a significant impact on patient
      adherence and consequently, on the safety and efficacy of a medicinal product.
      Palatability encompasses properties of medicines not limited to taste including
      swallowability (e.g. size, shape, texture). However, there has been limited work
      undertaken to measure the texture of medicines and how this may affect
      palatability and subsequent adherence. Tribology offers an understanding of oral
      processes and can allow physical properties of materials to be linked to
      "mouthfeel". This paper describes a preliminary application of tribology to oral
      liquid medicines and demonstrates that this technique is useful in the
      development of future oral liquid medicines. 

PMID- 25575473
TI  - Formulation and process optimization of multiparticulate pulsatile system
      delivered by osmotic pressure-activated rupturable membrane.
AB  - In this study, a multiparticulate pulsatile drug delivery system activated by a
      rupturable controlled-release membrane (Eudragit((r)) RS) via osmotic pressure
      (with NaCl as the osmogent) was developed and characterized for omeprazole,
      omeprazole sodium, and propranolol HCl which have different water solubilities.
      Multiparticulates in pellet form for incorporation with or without the osmogent
      were manufactured by three methods and then used to coat a polymeric membrane.
      Results demonstrated that drug/osmogent-containing pellets manufactured by the
      extrusion/spheronization method with incorporation of the osmogent were optimal.
      The lag time (tL) to initiate pulsatile release is regulated by tL=l(2)/(6*D),
      which is dependent on the coating levels (l(2)) and plasticizer content (D). The
      pulsatile release pattern was found to be dependent on the osmotic pressure
      (osmogent), drug solubility, and mechanical properties of the polymeric membrane
      (elasticity and toughness). Omeprazole with lower water solubility could not
      generate sufficient osmotic pressure to create a crack in the membrane to
      activate pulsatile release, whereas the two other model drugs with higher
      solubilities could. But adsorption of omeprazole sodium on Eudragit((r)) RS via
      charge-charge interactions led the its incomplete release. Finally, with 4%
      osmogent of NaCl added, a lag time in a range from 0 to 12h proportionally
      regulated by varying both the membrane thickness and plasticizer level initiated
      the complete pulsatile release of propranolol HCl. In conclusion, a
      multiparticulate pulsatile drug delivery system activated by a rupturable
      controlled-release membrane via osmotic pressure was successfully developed, and
      clinical applications of chronotherapy with drugs like propranolol HCl are
      expected. 

PMID- 25575472
TI  - Protein release from water-swellable poly(D,L-lactide-PEG)-b-poly(epsilon
      caprolactone) implants.
AB  - In this study, water-swellable multiblock copolymers composed of semi-crystalline
      poly(epsilon-caprolactone) [PCL] blocks and amorphous blocks consisting of
      poly(D,L-lactide) (PDLLA) and poly(ethylene glycol) (PEG) [PDLLA-PEG] were
      synthesized. The block ratio of these [PDLLA-PEG]-b-[PCL] multiblock copolymers
      was varied and the degradation of implants prepared of these polymers by hot melt
      extrusion (HME) was compared with implants prepared of [PCL-PEG]-b-[PCL], a
      copolymer which has been described previously (Stankovic et al., 2014). It was
      shown that the initial degradation rate of the [PDLLA-PEG]-b-[PCL] multiblock
      copolymers increased with increasing the content of amorphous [PDLLA-PEG] block
      and that the degradation rate of these multiblock copolymers was faster than that
      of the [PCL-PEG]-b-[PCL] multiblock copolymers due to rapid degradation of the
      [PDLLA-PEG] block. Furthermore, the release of the model proteins lysozyme and
      bovine serum albumin from polymer implants prepared by HME was studied. It was
      found that the protein release from [PDLLA-PEG]-b-[PCL] copolymers was
      incomplete, which is not acceptable for any application of these polymers.
      Besides, [PCL-PEG]-b-[PCL] copolymers showed slow and continuous release. We
      hypothesize that the incomplete release is explained by an irreversible
      interaction between the proteins and polymer degradation products or by
      entrapment of the protein in the hydrophobic and non-swellable polymer matrix
      that was left after degradation and loss of the hydrophilic [PDLLA-PEG] blocks
      from the degrading polymer.

PMID- 25575474
TI  - Dramatic improvement of the solubility of pseudolaric acid B by cyclodextrin
      complexation: preparation, characterization and validation.
AB  - As one of the most important technologies to improve the solubility of poorly
      water-soluble drugs, the solubilization effects of cyclodextrins (CDs)
      complexation are, on occasions, not as large as expected, which tends to detract
      from the wider application of CDs. In this study, a dramatic improvement of the
      solubility of pseudolaric acid B (PAB) by CDs has been found with a 600 fold
      increase by HP-beta-CD complexation. In addition, the solubility enhancement of
      PAB by various CDs, including alpha-CD, beta-CD, gamma-CD, HP-beta-CD and SBE
      beta-CD was investigated by phase solubility studies. The inclusion complex of
      PAB/HP-beta-CD was prepared by different methods and characterized by
      differential scanning calorimetry (DSC), powder X-ray diffractometry (XRD),
      nuclear magnetic resonance spectroscopy ((1)H NMR) together with molecular
      simulation. The results indicated that the solubility of PAB was increased to
      15.78mgmL(-1) in the presence of 30% HP-beta-CD, which is a 600 fold increase
      compared with that in pure water. And the chemical stability of PAB in PBS (pH
      7.4) can be enhanced. The results of DSC and XRD showed the absence of
      crystallinity in the PAB/HP-beta-CD inclusion complex prepared by the saturated
      water solution method. The results of (1)H NMR together with molecular simulation
      indicated the conjugated diene side-chain of PAB was included into the cavity of
      HP-beta-CD, with the free energy of -20.34+/-4.69kJmol(-1). While the enzymatic
      degradation site of the carboxyl polar bond is located in the hydrophilic outer
      of HP-beta-CD resulted in no significant difference for the enzymatic degradation
      rate between PAB and PAB/HP-beta-CD complexes in rat plasma. In summary, the
      PAB/HP-beta-CD inclusion complex prepared in this study can greatly improve the
      solubility and chemical stability of PAB, which will result in the in vivo
      administration of PAB as a liquid solution. 

PMID- 25575475
TI  - Successful partnerships with third sector organisations to enhance the healthcare
      student experience: a partnership evaluation.
AB  - There is limited research surrounding academic partnerships and more research is
      needed to educate universities, and the private, public and third sectors about
      the benefits and limitations of such partnerships. The aim of this study was to
      outline the unique partnership between Macmillan Cancer Support and De Montfort
      University and to evaluate the progress of this partnership. A qualitative
      approach was employed which involved interviews with nine members of the
      partnership's steering group. Interviews were transcribed and analysed using
      thematic analysis. The results showed that a partnership between a university and
      a third sector charity can have mutual benefits for all those involved,
      particularly for students and those affected by cancer. Furthermore, the module
      to develop volunteering among families affected cancer, created through this
      partnership is now being considered by other universities as a way of providing
      holistic and non-traditional lecture based learning experiences. Recommendations
      are made for future partnerships between third sector charities and universities.

PMID- 25575477
TI  - Edwardsiella tarda evades serum killing by preventing complement activation via
      the alternative pathway.
AB  - Edwardsiella tarda is a Gram-negative bacterium with a broad host range that
      includes a wide variety of farmed fish as well as humans. E. tarda has long been
      known to be able to survive in host serum, but the relevant mechanism is unclear.
      In this study, we investigated the fundamental question, i.e. whether E. tarda
      activated serum complement or not. We found that (i) when incubated with flounder
      serum, E. tarda exhibited a high survival rate (87.6%), which was slightly but
      significantly reduced in the presence of Mg(2+); (ii) E. tarda-incubated serum
      possessed strong hemolytic activity and bactericidal activity, (iii) compared to
      the serum incubated with a complement-sensitive laboratory Escherichia coli
      strain, E. tarda-incubated serum exhibited much less chemotactic activity, (iv)
      in contrast to the serum incubated with live E. tarda, the serum incubated with
      heat-inactivated E. tarda exhibited no apparent hemolytic capacity. Taken
      together, these results indicate for the first time that E. tarda circumvents
      serum attack by preventing, to a large extent, complement activation via the
      alternative pathway, and that heat-labile surface structures likely play an
      essential role in the complement evasion of E. tarda.

PMID- 25575476
TI  - Macrobrachium rosenbergii mannose binding lectin: synthesis of MrMBL-N20 and
      MrMBL-C16 peptides and their antimicrobial characterization, bioinformatics and
      relative gene expression analysis.
AB  - Mannose-binding lectin (MBL), an antimicrobial protein, is an important component
      of innate immune system which recognizes repetitive sugar groups on the surface
      of bacteria and viruses leading to activation of the complement system. In this
      study, we reported a complete molecular characterization of cDNA encoded for MBL
      from freshwater prawn Macrobrachium rosenbergii (Mr). Two short peptides (MrMBL
      N20: (20)AWNTYDYMKREHSLVKPYQG(39) and MrMBL-C16: (307)GGLFYVKHKEQQRKRF(322)) were
      synthesized from the MrMBL polypeptide. The purity of the MrMBL-N20 (89%) and
      MrMBL-C16 (93%) peptides were confirmed by MS analysis (MALDI-ToF). The purified
      peptides were used for further antimicrobial characterization including minimum
      inhibitory concentration (MIC) assay, kinetics of bactericidal efficiency and
      analysis of hemolytic capacity. The peptides exhibited antimicrobial activity
      towards all the Gram-negative bacteria taken for analysis, whereas they showed
      the activity towards only a few selected Gram-positive bacteria. MrMBL-C16
      peptides produced the highest inhibition towards both the Gram-negative and Gram
      positive bacteria compared to the MrMBL-N20. Both peptides do not produce any
      inhibition against Bacillus sps. The kinetics of bactericidal efficiency showed
      that the peptides drastically reduced the number of surviving bacterial colonies
      after 24 h incubation. The results of hemolytic activity showed that both
      peptides produced strong activity at higher concentration. However, MrMBL-C16
      peptide produced the highest activity compared to the MrMBL-N20 peptide. Overall,
      the results indicated that the peptides can be used as bactericidal agents. The
      MrMBL protein sequence was characterized using various bioinformatics tools
      including phylogenetic analysis and structure prediction. We also reported the
      MrMBL gene expression pattern upon viral and bacterial infection in M.
      rosenbergii gills. It could be concluded that the prawn MBL may be one of the
      important molecule which is involved in antimicrobial mechanism. Moreover, MrMBL
      derived MrMBL-N20 and MrMBL-C16 peptides are important antimicrobial peptides for
      the recognition and eradication of viral and bacterial pathogens. 

PMID- 25575478
TI  - Optimal area of retinal photocoagulation necessary for suppressing active iris
      neovascularization associated with diabetic retinopathy.

PMID- 25575482
TI  - Cocytus: Have you begun your descent?
AB  - The vast majority of trainees entering a fellowship express a sincere interest in
      pursuing an 'academic career'. However, even the most dedicated souls will find
      their own path toward that worthy goal fraught with a number of unanticipated
      hazards--any one of which could result in a fullstop of professional advancement.
      Of interest, many of the obstacles are actually self-imposed, usually buried
      within the subconscious self. Without guidance of how to recognize and address
      these shortcomings, abandonment of one's original career trajectory may be
      seriously considered, and often acted upon. By the time any one of us has
      completed training, taken the boards, and gotten to this inflection point, we are
      at least in our mid- to late-30s. What then, is there to do, about this looming
      phenomenon, whenever it may occur? Perhaps we can draw comfort from a historical
      figure who has been there, and done that. His journey embodies the value of
      mentoring in traversing the succession of personal perils that are commonplace in
      today's professional environment.

PMID- 25575479
TI  - New hypothesis and treatment targets of depression: an integrated view of key
      findings.
AB  - Major depressive disorder (MDD) is a common and devastating psychiatric disorder
      characterized by persistent low mood, cognitive disorder, and impaired social
      function. Despite its complex mechanisms, increasing evidence has identified the
      involvement of neurotrophic factors, inflammatory cytokines, the hypothalamus
      pituitary-adrenal axis, and glutamate receptors in the pathophysiology of this
      illness. The present review synthesizes recent research achievements to define
      the network between different hypotheses of MDD and to understand which part is
      most pivotal for its pathogenesis. By integrating MDD-related signal pathways, we
      highlight brain-derived neurotrophic factor (BDNF) dysfunction and increased
      apoptosis as the final common cascades, and new therapeutic strategies aiming to
      enhance BDNF function have been shown to exert a rapid and effective
      antidepressant action. 

PMID- 25575484
TI  - Foreword.

PMID- 25575480
TI  - Path from schizophrenia genomics to biology: gene regulation and perturbation in
      neurons derived from induced pluripotent stem cells and genome editing.
AB  - Schizophrenia (SZ) is a devastating mental disorder afflicting 1% of the
      population. Recent genome-wide association studies (GWASs) of SZ have identified
      >100 risk loci. However, the causal variants/genes and the causal mechanisms
      remain largely unknown, which hinders the translation of GWAS findings into
      disease biology and drug targets. Most risk variants are noncoding, thus likely
      regulate gene expression. A major mechanism of transcriptional regulation is
      chromatin remodeling, and open chromatin is a versatile predictor of regulatory
      sequences. MicroRNA-mediated post-transcriptional regulation plays an important
      role in SZ pathogenesis. Neurons differentiated from patient-specific induced
      pluripotent stem cells (iPSCs) provide an experimental model to characterize the
      genetic perturbation of regulatory variants that are often specific to cell type
      and/or developmental stage. The emerging genome-editing technology enables the
      creation of isogenic iPSCs and neurons to efficiently characterize the effects of
      SZ-associated regulatory variants on SZ-relevant molecular and cellular
      phenotypes involving dopaminergic, glutamatergic, and GABAergic
      neurotransmissions. SZ GWAS findings equipped with the emerging functional
      genomics approaches provide an unprecedented opportunity for understanding new
      disease biology and identifying novel drug targets. 

PMID- 25575483
TI  - Adjuvant vaginal brachytherapy decreases the risk of vaginal recurrence in
      patients with stage I non-invasive uterine papillary serous carcinoma. A multi
      institutional study.
AB  - OBJECTIVES: To investigate the impact of adjuvant vaginal brachytherapy on
      vaginal recurrence in stage I non-invasive uterine papillary serous carcinoma
      (UPSC). METHODS: This is a retrospective multi-institutional study from 2000
      2012. 103 patients who underwent surgical treatment with non-invasive stage IA
      UPSC were included. RESULTS: 85% and 55% underwent staging lymphadenectomy and
      omentectomy respectively. 28.2% (29/103) developed recurrence. Vaginal, pelvic
      and extra-pelvic recurrences developed in 7.8% (8/103), 3.9% (4/103) and 16.5%
      (17/103) respectively. Among patients who were observed or received only
      chemotherapy, the rate of vaginal recurrence was 10.9% (7/64) compared to 2.6%
      (1/39) among those who received vaginal brachytherapy +/- chemotherapy (p=0.035).
      The rate of vaginal recurrence was not different between those who were observed
      and those who received only chemotherapy (9.3% vs. 14.3%, p=0.27). The 5-year
      progression free survival (PFS) and overall survival (OS) for the entire cohort
      were 88.3% and 90.6%. Patients who underwent surgical staging had longer PFS
      (p=0.001) and OS (p=0.0005) compared to those who did not. In multivariable
      analysis controlling for age, histology, chemotherapy, brachytherapy, and staging
      lymphadenectomy, only lymphadenectomy was an independent predictor of PFS (HR
      0.28, 95% CI 0.11-0.71, p=0.0037) and OS (HR 0.27, 95% CI 0.10-0.71, p=0.0035).
      Neither chemotherapy nor brachytherapy were predictors of PFS or OS. CONCLUSIONS:
      This is the largest study reported in stage I non-invasive UPSC. The majority of
      recurrences were extra-pelvic. Vaginal brachytherapy has a significant role in
      reducing the risk of vaginal recurrence and surgical staging was the only
      predictor of outcome. Therefore, both should be considered in these patients.

PMID- 25575481
TI  - High versus low-dose rate brachytherapy for cervical cancer.
AB  - OBJECTIVES: Brachytherapy plays an important role in the treatment of cervical
      cancer. While small trials have shown comparable survival outcomes between high
      (HDR) and low-dose rate (LDR) brachytherapy, little data is available in the US.
      We examined the utilization of HDR brachytherapy and analyzed the impact of type
      of brachytherapy on survival for cervical cancer. METHODS: Women with stages IB2
      IVA cervical cancer treated with primary (external beam and brachytherapy)
      radiotherapy between 2003-2011 and recorded in the National Cancer Database
      (NCDB) were analyzed. Generalized linear mixed models and Cox proportional
      hazards regression were used to examine predictors of HDR brachytherapy use and
      the association between HDR use and survival. RESULTS: A total of 10,564 women
      including 2681 (25.4%) who received LDR and 7883 (74.6%) that received HDR were
      identified. Use of HDR increased from 50.2% in 2003 to 83.9% in 2011 (P<0.0001).
      In a multivariable model, year of diagnosis was the strongest predictor of use of
      HDR. While patients in the Northeast were more likely to receive HDR therapy,
      there were no other clinical or socioeconomic characteristics associated with
      receipt of HDR. In a multivariable Cox model, survival was similar between the
      HDR and LDR groups (HR=0.93; 95% CI 0.83-1.03). Similar findings were noted in
      analyses stratified by stage and histology. Kaplan-Meier analyses demonstrated no
      difference in survival based on type of brachytherapy for stage IIB (P=0.68),
      IIIB (P=0.17), or IVA (P=0.16) tumors. CONCLUSIONS: The use of HDR therapy has
      increased rapidly. Overall survival is similar for LDR and HDR brachytherapy.

PMID- 25575485
TI  - Comparison of content and in vitro bioaccessibility of provitamin A carotenoids
      in home cooked and commercially processed orange fleshed sweet potato (Ipomea
      batatas Lam).
AB  - Vitamin A deficiency (VAD) remains a public health problem in some regions of
      Brazil. Increased use of orange-fleshed sweet potato (OFSP) as a source of pro
      vitamin A represents a potential strategy for prevention of VAD. We compared the
      pro-vitamin A content, vitamin A equivalency and bioaccessibility of beta
      carotene (betaC) of two varieties of home cooked OFSP and two commercial sources
      of processed OFSP. Pro-vitamin A carotenoid content in home cooked, Beauregard
      variety of OFSP exceeded that in Amelia variety and commercial products for
      babies. All-trans-betaC was the most abundant carotenoid in raw, cooked and
      commercial OFSP. Boiling and frying OFSP generally decreased total betaC. A
      serving of 100 g FW Beauregard variety of cooked OFSP contained greater than 100%
      of the estimated average requirement (EAR) for children and women, and up to 92%
      EAR for lactating women. Although the efficiency of micellarization of all-trans
      betaC during simulated digestion of OFSP was relatively low (4-8%) and
      significantly less than for cis-isomers, the quantities of trans-betaC
      incorporated into micelles from boiled Beauregard and fried Amelia varieties
      exceeded that in micelles generated by digesting commercial OFSP. The
      bioaccessibility of pro-vitamin A carotenoids in the micelle fraction of digested
      OFSP was confirmed with differentiated cultures of Caco-2 human intestinal cells.
      Continued development of OFSP such as the Amelia and Beauregard varieties that
      are rich in trans-betaC and dissemination of best practices for home cooking are
      encouraged to increase consumption of this food to decrease the risk of vitamin A
      deficiency in Brazil.

PMID- 25575486
TI  - Evaluation of the total antioxidant capacity, polyphenol contents and starch
      hydrolase inhibitory activity of ten edible plants in an in vitro model of
      digestion.
AB  - The total phenolics contents, total antioxidant capacity (TAC) and starch
      hydrolase inhibitory activity of the aqueous extracts of 10 edible plants and the
      stability of these parameters after the gastric and duodenal digestion in an in
      vitro model was investigated. The TAC was evaluated using the oxygen radical
      absorbance capacity (ORAC) assay, ferric reducing antioxidant power (FRAP) and 2,
      2-diphenyl-1-picrylhydrazyl (DPPH*) and 2, 2-azinobis-(3-ethylbenzothiazoline-6
      sulfonic acid) (ABTS*+) radical scavenging assays. Characterization and
      quantification of five polyphenol compounds which were previously identified to
      be present in all the selected plants were carried out. None of the extracts
      showed a decrease in the total phenolics content or the ORAC and FRAP values
      following digestion. None of the quantified phenolic compounds had decreased
      during any of the digestion phases - an observation which was deemed as
      beneficial in terms of therapeutic properties. Overall, the parameters analyzed
      were relatively stable throughout the digestive process in all the extracts. 

PMID- 25575487
TI  - Variation in nutritional quality and chemical composition of fresh strawberry
      fruit: combined effect of cultivar and storage.
AB  - Bioclimatic air ionisation system (BI) works by neutralising air pollutants and
      microorganisms by means of oxidation with "activated oxygen". We investigated the
      effects of storage on changes in weight loss, chemical and sensory fruit
      properties in eight cultivars of strawberries (Fragaria x ananassa Duch.). All
      cultivars were evaluated for their standard parameters of quality (soluble solids
      content, total acidity, vitamin C content, total antioxidant activity - TAC,
      total phenolic and anthocyanins content) at different store conditions: fresh
      fruits-control, cold stored (at 4  degrees C) fruits without controlled
      atmospheres and cold stored (at 4  degrees C) fruits in BI. The present study
      outlines that anthocyanins of the strawberries stored in BI were subjected to
      significant degradation. These strawberries have prolonged shelf-life accompanied
      by weight loss reduction, TAC increment, and sensory properties improvement in
      tested cultivars, retaining other nutritional fruit qualities.

PMID- 25575488
TI  - A randomized, double-blind, duloxetine-referenced study comparing efficacy and
      tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults
      with MDD.
AB  - RATIONALE: Vortioxetine has reduced depressive symptoms in adults with major
      depressive disorder (MDD) in multiple clinical trials. OBJECTIVES: The aim of
      this study is to evaluate the efficacy, safety, and tolerability of vortioxetine
      15 and 20 mg vs placebo in adults with MDD. METHODS: Patients were randomized
      1:1:1:1 to vortioxetine 15 mg, vortioxetine 20 mg, duloxetine 60 mg (active
      reference), or placebo. The primary efficacy endpoint was mean change in
      Montgomery-Asberg Depression Rating Scale (MADRS) total score at week 8 (MMRM).
      Safety/tolerability assessments included physical examinations, vital signs,
      laboratory evaluations, electrocardiograms, adverse events (AEs), Columbia
      Suicide Severity Rating Scale, Arizona Sexual Experiences Scale, and
      Discontinuation-Emergent Signs and Symptoms checklist. RESULTS: Six hundred and
      fourteen patients were randomized. Mean changes in MADRS scores were -12.83 (+/
      0.834), -14.30 (+/-0.890), -15.57 (+/-0.880), and -16.90 (+/-0.884) for placebo,
      vortioxetine 15 mg (P = .224), vortioxetine 20 mg (P = .023), and duloxetine 60
      mg (P < .001) (P vs placebo), respectively. AEs reported by >=5 % of vortioxetine
      patients included nausea, headache, diarrhea, dizziness, dry mouth, constipation,
      vomiting, insomnia, fatigue, and upper respiratory infection. Treatment-emergent
      sexual dysfunction, suicidal ideation or behavior, and discontinuation symptoms
      were not significantly different between vortioxetine and placebo. CONCLUSIONS:
      Vortioxetine 20 mg significantly reduced MADRS total scores after 8 weeks of
      treatment. Both vortioxetine doses were well tolerated. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov identifier NCT01153009; www.clinicaltrials.gov/
      .

PMID- 25575489
TI  - Reductions in synaptic proteins and selective alteration of prepulse inhibition
      in male C57BL/6 mice after postnatal administration of a VIP receptor (VIPR2)
      agonist.
AB  - RATIONALE: An abundance of genetic and epidemiologic evidence as well as
      longitudinal neuroimaging data point to developmental origins for schizophrenia
      and other mental health disorders. Recent clinical studies indicate that
      microduplications of VIPR2, encoding the vasoactive intestinal peptide (VIP)
      receptor VPAC2, confer significant risk for schizophrenia and autism spectrum
      disorder. Lymphocytes from patients with these mutations exhibited higher VIPR2
      gene expression and VIP responsiveness (cAMP induction), but mechanisms by which
      overactive VPAC2 signaling may lead to these psychiatric disorders are unknown.
      OBJECTIVES: We subcutaneously administered the highly selective VPAC2 receptor
      agonist Ro 25-1553 to C57BL/6 mice from postnatal day 1 (P1) to P14 to determine
      if overactivation of VPAC2 receptor signaling during postnatal brain maturation
      affects synaptogenesis and selected behaviors. RESULTS: Western blot analyses on
      P21 revealed significant reductions of synaptophysin and postsynaptic density
      protein 95 (PSD-95) in the prefrontal cortex, but not in the hippocampus in Ro 25
      1553-treated mice. The same postnatally restricted treatment resulted in a
      disruption in prepulse inhibition of the acoustic startle measured in adult mice.
      No effects were observed in open-field locomotor activity, sociability in the
      three-chamber social interaction test, or fear conditioning or extinction.
      CONCLUSION: Overactivation of the VPAC2 receptor in the postnatal mouse results
      in a reduction in synaptic proteins in the prefrontal cortex and selective
      alterations in prepulse inhibition. These findings suggest that the VIPR2-linkage
      to mental health disorders may be due in part to overactive VPAC2 receptor
      signaling during a critical time of synaptic maturation.

PMID- 25575490
TI  - Leucine supplementation does not affect protein turnover and impairs the
      beneficial effects of endurance training on glucose homeostasis in healthy mice.
AB  - Endurance exercise training as well as leucine supplementation modulates glucose
      homeostasis and protein turnover in mammals. Here, we analyze whether leucine
      supplementation alters the effects of endurance exercise on these parameters in
      healthy mice. Mice were distributed into sedentary (C) and exercise (T) groups.
      The exercise group performed a 12-week swimming protocol. Half of the C and T
      mice, designated as the CL and TL groups, were supplemented with leucine (1.5 %
      dissolved in the drinking water) throughout the experiment. As well known,
      endurance exercise training reduced body weight and the retroperitoneal fat pad,
      increased soleus mass, increased VO2max, decreased muscle proteolysis, and
      ameliorated peripheral insulin sensitivity. Leucine supplementation had no effect
      on any of these parameters and worsened glucose tolerance in both CL and TL mice.
      In the soleus muscle of the T group, AS-160(Thr-642) (AKT substrate of 160 kDa)
      and AMPK(Thr-172) (AMP-Activated Protein Kinase) phosphorylation was increased by
      exercise in both basal and insulin-stimulated conditions, but it was reduced in
      TL mice with insulin stimulation compared with the T group. Akt phosphorylation
      was not affected by exercise but was lower in the CL group compared with the
      other groups. Leucine supplementation increased mTOR phosphorylation at basal
      conditions, whereas exercise reduced it in the presence of insulin, despite no
      alterations in protein synthesis. In trained groups, the total FoxO3a protein
      content and the mRNA for the specific isoforms E2 and E3 ligases were reduced. In
      conclusion, leucine supplementation did not potentiate the effects of endurance
      training on protein turnover, and it also reduced its positive effects on glucose
      homeostasis. 

PMID- 25575491
TI  - Independent and co-morbid HIV infection and Meth use disorders on oxidative
      stress markers in the cerebrospinal fluid and depressive symptoms.
AB  - Both HIV infection and Methamphetamine (Meth) use disorders are associated with
      greater depressive symptoms and oxidative stress; whether the two conditions
      would show additive or interactive effects on the severity of depressive
      symptoms, and whether this is related to the level of oxidative stress in the CNS
      is unknown. 123 participants were evaluated, which included 41 HIV-seronegative
      subjects without substance use disorders (Control), 25 with recent (<6 months)
      moderate to severe Meth use disorders (Meth), 34 HIV-seropositive subjects
      without substance use disorders (HIV) and 23 HIV+Meth subjects. Depressive
      symptoms were assessed with the Center for Epidemiologic Studies-Depression Scale
      (CES-D), and oxidative stress markers were evaluated with glutathione (GSH), 4
      hydroxynonenal (HNE), and activities of gamma-glutamyltransferase (GGT) and
      glutathione peroxidase (GPx) in the cerebrospinal fluid (CSF). Compared with
      Controls, HIV subjects had higher levels of HNE (+350%) and GGT (+27%), and lower
      level of GSH (-34%), while Meth users had higher levels of GPx activity (+23%)
      and GSH (+30 %). GGT correlated with GPx, and with age, across all subjects (p <
      0.0001). CES-D scores correlated with CSF HNE levels only in Control and HIV
      groups, but not in Meth and HIV+Meth groups. HIV and Meth use had an interactive
      effects on depressive symptoms, but did not show additive or interactive effects
      on oxidative stress. The differential relationship between depressive symptoms
      and oxidative stress response amongst the four groups suggest that depressive
      symptoms in these groups are mediated through different mechanisms which are not
      always related to oxidative stress.

PMID- 25575492
TI  - PPARalpha signaling in the hippocampus: crosstalk between fat and memory.
AB  - Major functions of the hippocampus are to generate, organize and store memory.
      This is a complex process, which is orchestrated by a group of molecules, called
      plasticity-related molecules. To control these various plasticity-related
      molecules at the transcriptional level, we have been endowed with cAMP response
      element-binding protein (CREB), also known as a master regulator of memory.
      Interestingly, we have seen that this master regulator is regulated at the
      transcriptional level in the hippocampus by peroxisome proliferator-activated
      receptor alpha (PPARalpha), a nuclear hormone receptor family transcription
      factor that is known to control the metabolism of fatty acids in the liver,
      underlying a possible crosstalk between fat and memory. Although liver PPARalpha
      does not directly control hippocampal CREB, this opens up an important
      possibility to improve hippocampal functions and to be resistant to memory loss
      by PPARalpha ligands and maintaining normal levels of PPARalpha in the
      hippocampus. 

PMID- 25575494
TI  - Bioethics, population studies, and geneticophobia.
AB  - In any research of human populations, the classical principles of bioethics
      (respect for autonomy, non-maleficence, beneficence, proportionality between
      risks and benefits, and justice) should be strictly followed. The question of
      individual and/or community rights should also be considered, as well as some
      neglected rights, such as the right to benefit from progress in science and
      technology and the right to know the nature of the group's biological and
      cultural history; however, in their urge to assure rights, social researchers,
      bioethics commissions, non-governmental organizations, and community leaders are,
      in many cases, crossing the limits of good sense. DNA is sometimes interpreted as
      synonymous to demoniac, and there is a frequent behaviour that I could only
      describe using a neologism: geneticophobia. There is an irrational attitude
      against genetic studies aiming to unravel the biological history of a given
      people and to classify any genome population study as "racist". This behaviour
      should be opposed; science and the scientific study of humankind are the only way
      we have to reach the socially adequate objective of the maximum of happiness to
      the largest number of persons. 

PMID- 25575493
TI  - Clinical characteristics of anastomotic leakage after an anterior resection for
      rectal cancer by assessing of the international classification on anastomotic
      leakage.
AB  - PURPOSE: The International Study Group of Rectal Cancer (ISREC) has proposed a
      new definition of anastomotic leakage (AL) which was simply classified into three
      grades; however, these criteria have not been assessed well. The aims of this
      study are to assess the new definition and to show the clinical features of AL
      after an anterior resection for rectal cancer. METHODS: Fifty consecutive
      patients developed AL after an anterior resection for rectal cancer was
      retrospectively assessed. AL was defined by the ISREC criteria. RESULTS: Twenty
      seven (54 %) patients with AL were diagnosed by drain contents. The postoperative
      day of diagnosis for AL was later in grade A versus grades B and C (p = 0.038 vs
      p = 0.006, respectively). Permanent stoma (PS) was significantly more frequent in
      patients with grade C but not grade B compared to the patients with no AL (p <
      0.001 and p = 0.171, respectively). In patients without diverting stoma, there
      was more serious grade of AL (p < 0.001). CONCLUSIONS: Differences were observed
      in the postoperative day of diagnosis, the creation rate of PS, and impact on
      diverting stoma after AL between each grade of leakage. The new classification
      was easy and reasonable to evaluate AL. As a result, it should be widely used in
      future studies.

PMID- 25575495
TI  - Phylloides tumours of the breast: best practice for follow-up.
AB  - Phylloides tumours are rare fibroepithelial breast tumours accounting for 1% of
      breast cancers. No UK guidance exists on the assessment, treatment and follow-up
      of these patients. To assess the diagnostic accuracy of the clinical core biopsy
      compared to the gold standard excision biopsy and determine the current follow-up
      practice and recurrence rate of phylloides tumours across two UK hospital trusts.
      Multicentre retrospective analysis of all cases of phylloides tumours over 6
      years at Worcestershire Acute NHS Trust (WANHST) and Gloucestershire Hospitals
      NHS Trust (GHNHST). 94 Patients included. Mean age 48 years. Mean clinical and
      radiological size of lesions 31.7 and 35.4 mm, respectively, preoperative core
      biopsy sensitivity was 87% for WANHST and 74% for GHNHST with a positive
      predictive value of 90 and 100%, respectively. 29 Different follow-up regimes
      were observed from the practice of the 10 surgeons observed following diagnosis
      and resection of tumours. The follow-up length ranged from discharge following
      one post-operative clinic attendance to 5-year clinical and/or radiological
      follow-up. 4 Benign and 2 malignant recurrent phylloides tumours were seen. All
      benign recurrences were local and found independently of follow-up. The earliest
      benign phylloides recurrence was at 6 years and the latest at 10 years. There is
      no standard follow-up of benign or malignant phylloides tumours. This study
      suggests that in the benign group, the risk of recurrence is small. We advocate
      no routine follow-up of benign phylloides tumours.

PMID- 25575497
TI  - Practice Guideline Recommendations on Perioperative Fasting: A Systematic Review.
AB  - BACKGROUND: Traditionally, perioperative fasting consisted of being nil by mouth
      (NBM) from midnight before surgery and fasting postoperatively until recovery of
      bowel function. These outdated practices persist despite emerging evidence
      revealing that excessive fasting results in negative outcomes and delayed
      recovery. Various evidence-based, multimodal, enhanced recovery protocols
      incorporating minimized perioperative fasting have arisen to improve patient
      outcomes and streamline recovery, but implementation remains limited. This
      article aims to review current fasting guidelines, assess their quality,
      summarize relevant recommendations, and identify gaps in evidence. METHODS: A
      systematic literature search of Medline and CINAHL and a manual search of
      relevant websites identified guidelines containing suitable grading systems and
      fasting recommendations. Guideline quality was assessed using the Appraisal of
      Guidelines Research and Evaluation (AGREE) tool. Grading systems were
      standardized to the American Society for Parenteral and Enteral Nutrition format
      and recommendations summarized based on grading and guideline quality. RESULTS:
      Nineteen guidelines were included. Rigor of development scores ranged from 29%
      95%, with only 8 guidelines explicitly declaring the use of systematic
      methodology. Applicability scores were lowest, averaging 32%. Ten recommendation
      types were extracted and summarized. Strong and consistent evidence exists for
      the minimization of perioperative fasting, for a 2-hour preoperative fast after
      clear fluids, and for early recommencement of oral food and fluid intake
      postoperatively. CONCLUSIONS: This article presents several high-level
      recommendations ready for immediate implementation, while poorly graded and
      inconsistent recommendations reveal key areas for future research. Meanwhile,
      guideline quality requires improvement, especially regarding rigor of development
      and applicability, through systematic methodology, reporting transparency, and
      implementation strategies.

PMID- 25575498
TI  - Terence Stephenson: Ready to navigate stormy waters once again?

PMID- 25575496
TI  - Insights on the evolution of mycoparasitism from the genome of Clonostachys
      rosea.
AB  - Clonostachys rosea is a mycoparasitic fungus that can control several important
      plant diseases. Here, we report on the genome sequencing of C. rosea and a
      comparative genome analysis, in order to resolve the phylogenetic placement of C.
      rosea and to study the evolution of mycoparasitism as a fungal lifestyle. The
      genome of C. rosea is estimated to 58.3 Mb, and contains 14,268 predicted genes.
      A phylogenomic analysis shows that C. rosea clusters as sister taxon to plant
      pathogenic Fusarium species, with mycoparasitic/saprotrophic Trichoderma species
      in an ancestral position. A comparative analysis of gene family evolution reveals
      several distinct differences between the included mycoparasites. Clonostachys
      rosea contains significantly more ATP-binding cassette (ABC) transporters,
      polyketide synthases, cytochrome P450 monooxygenases, pectin lyases, glucose
      methanol-choline oxidoreductases, and lytic polysaccharide monooxygenases
      compared with other fungi in the Hypocreales. Interestingly, the increase of ABC
      transporter gene number in C. rosea is associated with phylogenetic subgroups B
      (multidrug resistance proteins) and G (pleiotropic drug resistance transporters),
      whereas an increase in subgroup C (multidrug resistance-associated proteins) is
      evident in Trichoderma virens. In contrast with mycoparasitic Trichoderma
      species, C. rosea contains very few chitinases. Expression of six group B and
      group G ABC transporter genes was induced in C. rosea during exposure to the
      Fusarium mycotoxin zearalenone, the fungicide Boscalid or metabolites from the
      biocontrol bacterium Pseudomonas chlororaphis. The data suggest that tolerance
      toward secondary metabolites is a prominent feature in the biology of C. rosea. 

PMID- 25575499
TI  - Development and validation of a predictive model for all-cause hospital
      readmissions in Winnipeg, Canada.
AB  - OBJECTIVE: A number of predictive models have been developed to identify patients
      at risk of hospital readmission. Most of these have focused on readmission within
      30 days of discharge. We used population-based health administrative data to
      develop a predictive model for hospital readmission within 12 months of discharge
      in Winnipeg, Canada. METHODS: This was a retrospective cohort study with
      derivation and validation data sets. Multivariable logistic regression analyses
      were performed and factors significantly associated with readmission were
      selected to construct a risk scoring tool. RESULTS: Several variables were
      identified that predicted readmission (i.e. older age, male, at least one
      hospital admission in the previous two years, an emergent (index) hospital
      admission, Charlson comorbidity score >0 and length of stay). Discrimination
      power was acceptable (C statistic =0.701). At a median risk score threshold, the
      sensitivity, specificity, positive and negative predictive values were 45.5%,
      79%, 68.8% and 58.6%. CONCLUSIONS: This predictive model demonstrated that
      hospital readmission within 12 months of discharge can be reasonably well
      predicted based on administrative data. It will help health care providers target
      interventions to prevent unnecessary hospital readmissions.

PMID- 25575500
TI  - Higher antihypertensive dose increases risk of falls in older people.

PMID- 25575502
TI  - Long-term survival in pre-specified groups at risk in the Oslo Study, 1972-1973.
AB  - AIMS: Using the Oslo Study of 1972-1973, we wished to compare the long-term
      mortality pattern up to 40 years, in both the healthy cardiovascular groups at
      supposedly high and low risk, and in some groups having cardiovascular disease at
      screening. METHODS: At the screening, 16,203 (63% of those invited) men aged 40
      49 years participated. Study groups were identified by means of questionnaires
      regarding diseases, blood pressure and measurements of total cholesterol,
      triglycerides and glucose. We identified six groups: very high cholesterol, very
      high blood pressure, very high glucose, non-smoking with non-elevated such risk
      factors, from a randomized diet and antismoking trial, and a randomized drug
      treatment in mild-to-moderate hypertension. Statistical analyses were by Cox
      regression analysis, with Kaplan-Meier graphs. RESULTS: The supposedly low-risk
      group had a total mortality of one-third of other groups, such as: men with
      hypertension, diabetes or hypercholesterolemia, or those whom participated in the
      two trials. Between these latter groups, we found 2-5 years of difference in
      their median survival time, but their absolute risk stayed at rather high levels
      through all the years, with the median remaining a lifetime that was 3-8 years
      shorter than the men whom were free of known cardiovascular disease, diabetes or
      hypertension. CONCLUSIONS: The long-term preventive effects on total mortality
      seem large, if the levels of the classical risk factors of blood pressure, total
      cholesterol and glucose can be adequately controlled, concurrently with a non
      smoking behavior. The study indicated that non-smoking and a low total
      cholesterol value were the most important contributors to extended survival.

PMID- 25575501
TI  - Long-term persistence of oral human papillomavirus type 16: the HPV Infection in
      Men (HIM) study.
AB  - Persistent infection with oral HPV16 is believed to drive the development of most
      oropharyngeal cancers. However, patterns of oral HPV16 persistence remain
      understudied, particularly among HIV-negative individuals. Oral HPV16 persistence
      was evaluated among 1,626 participants of the HPV Infection in Men (HIM) Study.
      Twenty-three oral HPV16-positive men who provided an oral gargle sample on >=2
      study visits were included in the analysis. Archived oral samples from all follow
      up visits were tested for HPV16 using Linear Array and INNO-LiPA detection
      methods. Persistence was evaluated using consecutive HPV16-positive visits held
      approximately 6 months apart and using the Kaplan-Meier method. Oral HPV16
      positive men were aged 18 to 64 years [median, 36 years; interquartile range
      (IQR), 25-42] and were followed for a median of 44.4 months (IQR, 29.9-49.5). Of
      13 incident infections, 4 (30.8%) persisted >=12 months, 1 (10.0%) persisted >=24
      months, and none persisted >=36 months [median infection duration, 7.3 months;
      95% confidence interval (CI), 6.4-NA)]. Of 10 prevalent infections, 9 (90.0%)
      persisted >=12 months, 8 (80.0%) persisted >=24 months, 4 (57.1%) persisted >=36
      months, and 2 (40.0%) persisted >=48 months (median infection duration, NA).
      Twelve-month persistence of incident infections increased significantly with age
      (Ptrend = 0.028). Prevalent oral HPV16 infections in men persisted longer than
      newly acquired infections, and persistence appeared to increase with age. These
      findings may explain the high prevalence of oral HPV observed at older ages.
      Understanding oral HPV16 persistence will aid in the identification of men at
      high-risk of developing HPV-related oropharyngeal cancer.

PMID- 25575503
TI  - The Effect of Parental Presence on Weight-Related Discussions Between Physicians
      and Their Overweight Adolescent Patients.

PMID- 25575505
TI  - Synergy in scientific publishing: the ESA-Oxford University Press Partnership.

PMID- 25575504
TI  - Age-dependent speciation can explain the shape of empirical phylogenies.
AB  - Tens of thousands of phylogenetic trees, describing the evolutionary
      relationships between hundreds of thousands of taxa, are readily obtainable from
      various databases. From such trees, inferences can be made about the underlying
      macroevolutionary processes, yet remarkably these processes are still poorly
      understood. Simple and widely used evolutionary null models are problematic:
      Empirical trees show very different imbalance between the sizes of the daughter
      clades of ancestral taxa compared to what models predict. Obtaining a simple
      evolutionary model that is both biologically plausible and produces the imbalance
      seen in empirical trees is a challenging problem, to which none of the existing
      models provide a satisfying answer. Here we propose a simple, biologically
      plausible macroevolutionary model in which the rate of speciation decreases with
      species age, whereas extinction rates can vary quite generally. We show that this
      model provides a remarkable fit to the thousands of trees stored in the online
      database TreeBase. The biological motivation for the identified age-dependent
      speciation process may be that recently evolved taxa often colonize new regions
      or niches and may initially experience little competition. These new taxa are
      thus more likely to give rise to further new taxa than a taxon that has remained
      largely unchanged and is, therefore, well adapted to its niche. We show that age
      dependent speciation may also be the result of different within-species
      populations following the same laws of lineage splitting to produce new species.
      As the fit of our model to the tree database shows, this simple biological
      motivation provides an explanation for a long standing problem in macroevolution.

PMID- 25575506
TI  - The Assisted Dying Bill and the role of the physician.
AB  - This article explores the role of the physician in the Assisted Dying Bill, which
      is currently progressing through the House of Lords. The Supreme Court decision
      in Nicklinson and Others has alerted Parliament to the possibility that the
      current prohibition against assisted suicide may breach Article 8 of the European
      Convention in relation to the right to choose how to end one's life. In this
      article, the role of healthcare professionals in the proposed legalisation of
      physician-assisted suicide is examined, together with consideration of key
      ethical concerns over who might be permitted to access assisted dying. Whether
      the proposed law presents an ethically sound alternative to the current
      prohibition against assisting in suicide is not clear, but Parliament must now
      respond in order to address human rights issues and the call to legalise
      medically assisted suicide. 

PMID- 25575507
TI  - Talking about death is not the same as communicating about death.

PMID- 25575508
TI  - A Rapid Centrifugation-Assisted Solid-Phase Extraction and Liquid Chromatography
      Method for Determination of Loureirin A and Loureirin B of Dragon's Blood
      Capsules in Rat Plasma and Urine After Oral Administration.
AB  - A simple, sensitive and rapid centrifugation-assisted solid-phase extraction
      (SPE) with high-performance liquid chromatography (SPE-HPLC) method was developed
      for simultaneous determination of the metabolites loureirin A and loureirin B
      from Dragon's blood in rat plasma and urine. The development of the extraction
      procedure included optimization of some important extraction phases. After
      evaluation, the metabolites of Dragon's blood were extracted by centrifugation
      assisted SPE and separated by using HPLC. This method showed good linearity (r(2)
      > 0.99), and in the rat plasma and urine, the recoveries were 93.1 and 95.7% for
      loureirin A and were 90.1 and 94.2% for loureirin B. The relative standard
      deviation (RSD) values of intraday and interday precision in rat plasma and urine
      for loureirin A were <3.84 and 2.01%, respectively. The RSD values of the
      intraday and interday precision in rat plasma and urine for loureirin B were
      below 4.25 and 5.83%, respectively. Thus, the established method is suitable for
      metabolism studies of loureirin A and loureirin B in rat plasma and urine. 

PMID- 25575509
TI  - Simultaneous Determination of Aliskiren Hemifumarate, Amlodipine Besylate and
      Hydrochlorothiazide in Spiked Human Plasma Using UPLC-MS/MS.
AB  - A sensitive UPLC-MS/MS method was developed and validated for simultaneous
      estimation of aliskiren hemifumarate (ALS), amlodipine besylate (AML) and
      hydrochlorothiazide (HCZ) in spiked human plasma using valsartan as an internal
      standard (IS). Liquid-liquid extraction was used for purification and pre
      concentration of analytes. The mobile phase consisted of 0.1% formic acid in
      ammonium acetate buffer (0.02 M, pH 3.5) and methanol (25:75, v/v), flowing
      through XBridge BEH (50 * 2.1 mm ID, 5 um) C18 column, at a flow rate of 0.6 mL
      min(-1). Multiple reaction monitoring (MRM) transitions were measured using an
      electrospray source in the positive ion mode for ALS and AML, whereas HCZ and IS
      were measured in negative ion mode. Validation of the method was performed as per
      US-FDA guidelines with linearity in the range of 2.0-400.0, 0.3-25.0 and 5.0
      400.0 ng mL(-1) for ALS, AML and HCZ, respectively. In human plasma, ALS, AML and
      HCZ were stable for at least 1 month at -70 +/- 5 degrees C and for at least 6 h
      at ambient temperature. After extraction from plasma, the reconstituted samples
      of ALS, AML and HCZ were stable in the autosampler at ambient temperature for 6
      h. The LC-MS/MS method is suitable for bioequivalence and pharmacokinetic studies
      of this combination. 

PMID- 25575510
TI  - Nucleolar stress and impaired stress granule formation contribute to C9orf72 RAN
      translation-induced cytotoxicity.
AB  - Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are the two
      common neurodegenerative diseases that have been associated with the
      GGGGCC.GGCCCC repeat RNA expansion in a noncoding region of C9orf72. It has been
      previously reported that unconventional repeat-associated non-ATG (RAN)
      translation of GGGGCC.GGCCCC repeats produces five types of dipeptide-repeat
      proteins (referred to as RAN proteins): poly-glycine-alanine (GA), poly-glycine
      proline (GP), poly-glycine-arginine (GR), poly-proline-arginine (PR) and poly
      proline-alanine (PA). Although protein aggregates of RAN proteins have been found
      in patients, it is unclear whether RAN protein aggregation induces neurotoxicity.
      In the present study, we aimed to understand the biological properties of all
      five types of RAN proteins. Surprisingly, our results showed that none of these
      RAN proteins was aggregate-prone in our cellular model and that the turnover of
      these RAN proteins was not affected by the ubiquitin-proteasome system or
      autophagy. Moreover, poly-GR and poly-PR, but not poly-GA, poly-GP or poly-PA,
      localized to the nucleolus and induced the translocation of the key nucleolar
      component nucleophosmin, leading to nucleolar stress and cell death. This poly-GR
      and poly-PR-mediated defect in nucleolar function was associated with the
      suppression of ribosomal RNA synthesis and the impairment of stress granule
      formation. Taken together, the results of the present study suggest a simple
      model of the molecular mechanisms underlying RAN translation-mediated
      cytotoxicity in C9orf72-linked ALS/FTD in which nucleolar stress, but not protein
      aggregation, is the primary contributor to C9orf72-linked neurodegeneration. 

PMID- 25575511
TI  - The RNA-binding protein Rbfox1 regulates splicing required for skeletal muscle
      structure and function.
AB  - The Rbfox family of RNA-binding proteins is highly conserved with established
      roles in alternative splicing (AS) regulation. High-throughput studies aimed at
      understanding transcriptome remodeling have revealed skeletal muscle as
      displaying one of the largest number of AS events. This finding is consistent
      with requirements for tissue-specific protein isoforms needed to sustain muscle
      specific functions. Rbfox1 is abundant in vertebrate brain, heart and skeletal
      muscle. Genome-wide genetic approaches have linked the Rbfox1 gene to autism, and
      a brain-specific knockout mouse revealed a critical role for this splicing
      regulator in neuronal function. Moreover, a Caenorhabditis elegans Rbfox1 homolog
      regulates muscle-specific splicing. To determine the role of Rbfox1 in muscle
      function, we developed a conditional knockout mouse model to specifically delete
      Rbfox1 in adult tissue. We show that Rbfox1 is required for muscle function but a
      >70% loss of Rbfox1 in satellite cells does not disrupt muscle regeneration. Deep
      sequencing identified aberrant splicing of multiple genes including those
      encoding myofibrillar and cytoskeletal proteins, and proteins that regulate
      calcium handling. Ultrastructure analysis of Rbfox1(-/-) muscle by electron
      microscopy revealed abundant tubular aggregates. Immunostaining showed
      mislocalization of the sarcoplasmic reticulum proteins Serca1 and Ryr1 in a
      pattern indicative of colocalization with the tubular aggregates. Consistent with
      mislocalization of Serca1 and Ryr1, calcium handling was drastically altered in
      Rbfox1(-/-) muscle. Moreover, muscle function was significantly impaired in
      Rbfox1(-/-) muscle as indicated by decreased force generation. These results
      demonstrate that Rbfox1 regulates a network of AS events required to maintain
      multiple aspects of muscle physiology. 

PMID- 25575513
TI  - Matrix metalloproteinase (MMP)-19-deficient fibroblasts display a profibrotic
      phenotype.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and usually lethal
      interstitial lung disease of unknown etiology characterized by aberrant
      activation of epithelial cells that induce the migration, proliferation and
      activation of fibroblasts. The resulting distinctive fibroblastic/myofibroblastic
      foci are responsible for the excessive extracellular matrix (ECM) production and
      abnormal lung remodeling. We have recently found that matrix metalloproteinase 19
      (MMP-19)-deficient (Mmp19-/-) mice develop an exaggerated bleomycin-induced lung
      fibrosis, but the mechanisms are unclear. In this study, we explored the effect
      of MMP-19 deficiency on fibroblast gene expression and cell behavior. Microarray
      analysis of Mmp19-/- lung fibroblasts revealed the dysregulation of several
      profibrotic pathways, including ECM formation, migration, proliferation, and
      autophagy. Functional studies confirmed these findings. Compared with wild-type
      mice, Mmp19-/- lung fibroblasts showed increased alpha1 (I) collagen gene and
      collagen protein production at baseline and after transforming growth factor-beta
      treatment and increased smooth muscle-alpha actin expression (P < 0.05).
      Likewise, Mmp19-deficient lung fibroblasts showed a significant increase in
      proliferation (P < 0.01) and in transmigration and locomotion over Boyden
      chambers coated with type I collagen or with Matrigel (P < 0.05). These findings
      suggest that, in lung fibroblasts, MMP-19 has strong regulatory effects on the
      synthesis of key ECM components, on fibroblast to myofibroblast differentiation,
      and in migration and proliferation. 

PMID- 25575512
TI  - Evidence for several independent genetic variants affecting lipoprotein (a)
      cholesterol levels.
AB  - Lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerosis-related
      events that is under strong genetic control (heritability = 0.68-0.98). However,
      causal mutations and functional validation of biological pathways modulating
      Lp(a) metabolism are lacking. We performed a genome-wide association scan to
      identify genetic variants associated with Lp(a)-cholesterol levels in the Old
      Order Amish. We confirmed a previously known locus on chromosome 6q25-26 and
      found Lp(a) levels also to be significantly associated with a SNP near the APOA5
      APOA4-APOC3-APOA1 gene cluster on chromosome 11q23 linked in the Amish to the
      APOC3 R19X null mutation. On 6q locus, we detected associations of Lp(a)
      cholesterol with 118 common variants (P = 5 * 10(-8) to 3.91 * 10(-19)) spanning
      a ~5.3 Mb region that included the LPA gene. To further elucidate variation
      within LPA, we sequenced LPA and identified two variants most strongly associated
      with Lp(a)-cholesterol, rs3798220 (P = 1.07 * 10(-14)) and rs10455872 (P = 1.85 *
      10(-12)). We also measured copy numbers of kringle IV-2 (KIV-2) in LPA using
      qPCR. KIV-2 numbers were significantly associated with Lp(a)-cholesterol (P =
      2.28 * 10(-9)). Conditional analyses revealed that rs3798220 and rs10455872 were
      associated with Lp(a)-cholesterol levels independent of each other and KIV-2 copy
      number. Furthermore, we determined for the first time that levels of LPA mRNA
      were higher in the carriers than non-carriers of rs10455872 (P = 0.0001) and were
      not different between carriers and non-carriers of rs3798220. Protein levels of
      apo(a) were higher in the carriers than non-carriers of both rs10455872 and
      rs3798220. In summary, we identified multiple independent genetic determinants
      for Lp(a)-cholesterol. These findings provide new insights into Lp(a) regulation.

PMID- 25575514
TI  - Airway responsiveness in CD38-deficient mice in allergic airway disease: studies
      with bone marrow chimeras.
AB  - CD38 is a cell-surface protein involved in calcium signaling and contractility of
      airway smooth muscle. It has a role in normal airway responsiveness and in airway
      hyperresponsiveness (AHR) developed following airway exposure to IL-13 and TNF
      alpha but appears not to be critical to airway inflammation in response to the
      cytokines. CD38 is also involved in T cell-mediated immune response to protein
      antigens. In this study, we assessed the contribution of CD38 to AHR and
      inflammation to two distinct allergens, ovalbumin and the epidemiologically
      relevant environmental fungus Alternaria. We also generated bone marrow chimeras
      to assess whether Cd38(+/+) inflammatory cells would restore AHR in the CD38
      deficient (Cd38(-/-)) hosts following ovalbumin challenge. Results show that wild
      type (WT) mice develop greater AHR to inhaled methacholine than Cd38(-/-) mice
      following challenge with either allergen, with comparable airway inflammation.
      Reciprocal bone marrow transfers did not change the native airway phenotypic
      differences between WT and Cd38(-/-) mice, indicating that the lower airway
      reactivity of Cd38(-/-) mice stems from Cd38(-/-) lung parenchymal cells.
      Following bone marrow transfer from either source and ovalbumin challenge, the
      phenotype of Cd38(-/-) hosts was partially reversed, whereas the airway phenotype
      of the WT hosts was preserved. Airway inflammation was similar in Cd38(-/-) and
      WT chimeras. These results indicate that loss of CD38 on hematopoietic cells is
      not sufficient to prevent AHR and that the magnitude of airway inflammation is
      not the predominant underlying determinant of AHR in mice. 

PMID- 25575515
TI  - Oxidized phospholipids protect against lung injury and endothelial barrier
      dysfunction caused by heat-inactivated Staphylococcus aureus.
AB  - Increased endothelial cell (EC) permeability and vascular inflammation along with
      alveolar epithelial damage are key features of acute lung injury (ALI). Products
      of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine oxidation (OxPAPC)
      showed protective effects against inflammatory signaling and vascular EC barrier
      dysfunction induced by gram-negative bacterial wall lipopolysaccharide (LPS). We
      explored the more general protective effects of OxPAPC and investigated whether
      delayed posttreatment with OxPAPC boosts the recovery of lung inflammatory injury
      and EC barrier dysfunction triggered by intratracheal injection of heat-killed
      gram-positive Staphylococcus aureus (HKSA) bacteria. HKSA-induced pulmonary EC
      permeability, activation of p38 MAP kinase and NF-kappaB inflammatory cascades,
      secretion of IL-8 and soluble ICAM1, fibronectin deposition, and expression of
      adhesion molecules ICAM1 and VCAM1 by activated EC were significantly attenuated
      by cotreatment as well as posttreatment with OxPAPC up to 16 h after HKSA
      addition. Remarkably, posttreatment with OxPAPC up to 24 h post-HKSA challenge
      dramatically accelerated lung recovery by restoring lung barrier properties
      monitored by Evans blue extravasation and protein content in bronchoalveolar
      lavage (BAL) fluid and reducing inflammation reflected by decreased MIP-1, KC,
      TNF-alpha, IL-13 levels and neutrophil count in BAL samples. These studies
      demonstrate potent in vivo and in vitro protective effects of posttreatment with
      anti-inflammatory oxidized phospholipids in the model of ALI caused by HKSA.
      These results warrant further investigations into the potential use of OxPAPC
      compounds combined with antibiotic therapies as a treatment of sepsis and ALI
      induced by gram-positive bacterial pathogens. 

PMID- 25575518
TI  - Effects of periodontal treatment on glycemic control in type 2 diabetic patients:
      a meta-analysis of randomized controlled trials.
AB  - The association between diabetes and inflammatory periodontal diseases has been
      studied extensively. However, there is a lack of robustness and homogeneity among
      studies describing effects of periodontal treatment on glycemic control. The aim
      of this study was to carry out a meta-analysis to understand whether periodontal
      treatment could improve glycemic control in type 2 diabetic patients. Electronic
      searches were carried out on MEDLINE, EMBASE and the Cochrane central register of
      controlled trials from 1980 to July 2012. Randomized controlled trials of
      periodontal therapy on glycemic control in diabetic patients with a minimum of 3
      months of follow-up were included. Meta-analysis was carried out with 8 studies
      involving 515 participants using Stata 11.0 software. Our results showed that
      periodontal treatment could lead to a significant decrease in HbA1c level. The
      standardized mean difference between intervention groups and control groups was
      significant: 1.03% (95% confidence interval: 0.31% to 1.70%, P = 0.003) from
      baseline to 3 months, and 1.18% (95% confidence interval: 0.72% to 1.64%, P <
      0.001) from baseline to 6 months. Periodontal treatment could lead to a non
      significant decrease in fasting plasma glucose (FPG) levels from baseline to 3
      months. The standardized mean difference between the intervention and the control
      group was 0.69 mg/dl (95% confidence interval: -0.27 mg/dl to 1.66 mg/dl, P =
      0.158). Our analysis indicated that periodontal treatment could improve glycemic
      control in type 2 diabetic patients with periodontal diseases. 

PMID- 25575517
TI  - Inhibition of protein phosphatase 1 reverses alcohol-induced ciliary dysfunction.
AB  - Airway mucociliary clearance is a first-line defense of the lung against inhaled
      particles and debris. Among individuals with alcohol use disorders, there is an
      increase in lung diseases. We previously identified that prolonged alcohol
      exposure impairs mucociliary clearance, known as alcohol-induced ciliary
      dysfunction (AICD). Cilia-localized enzymes, known as the ciliary metabolon, are
      key to the pathogenesis of AICD. In AICD, cyclic nucleotide-dependent ciliary
      kinases, which modulate phosphorylation to regulate cilia beat, are desensitized.
      We hypothesized that alcohol activates cilia-associated protein phosphatase 1
      (PP1) activity, driving phosphorylation changes of cilia motility regulatory
      proteins. To test this hypothesis we identified the effects of prolonged alcohol
      exposure on phosphatase activity, cilia beat, and kinase responsiveness and cilia
      associated phosphorylation targets when stimulated by beta-agonist or cAMP.
      Prolonged alcohol activated PP1 and blocked cAMP-dependent cilia beat and protein
      kinase A (PKA) responsiveness and phosphorylation of a 29-kDa substrate of PKA.
      Importantly, prolonged alcohol-induced phosphatase activation was inhibited by
      the PP1 specific inhibitor, inhibitor-2 (I-2), restoring cAMP-stimulated cilia
      beat and PKA responsiveness and phosphorylation of the 29-kDa substrate. The I-2
      inhibitory effect persisted in tissue, cell, and isolated cilia-organelle models,
      highlighting the association of ciliary metabolon-localized enzymes to AICD.
      Prolonged alcohol exposure drives ciliary metabolon-localized PP1 activation. PP1
      activation modifies phosphorylation of a 29-kDa protein related to PKA activity.
      These data reinforce our previous findings that alcohol is acting at the level of
      the ciliary metabolon to cause ciliary dysfunction and identifies PP1 as a
      therapeutic target to prevent or reverse AICD. 

PMID- 25575519
TI  - Training and cardiovascular responses from cigarette smoke exposure.
AB  - The aim of this study was to evaluate the early effect of the endurance training
      (ET) on systolic blood pressure (SBP), heart rate (HR) and rate pressure-product
      (RPP) after acute cigarette smoke exposure. Twenty male Wistar rats were randomly
      allocated into two groups: trained (TEx; n = 10) and control (CEx; n = 10),
      exposed to smoke. TEx rats undertook ET during 2 weeks (swimming, 5 days/week; 1
      h/session) and CEx group was kept in sedentary lifestyle. After ET protocol both
      groups were exposed to cigarette smoke only once (total 1 h; 2 * 30 min with
      interval of 10 min between exposures; rate of 10 cigarettes/30 min). SBP, HR and
      RPP were measured after 2 weeks and just after (5 min) acute cigarette smoke
      (tail plethysmograph). All parameters did not differ (P > 0.05) between TEx (RPP
      = 45018 +/- 1970 mmHg/bpm) and CEx (43695 +/- 2579 mmHg/bpm) after ET protocol.
      However, all cardiovascular parameters increased (P < 0.05) only for CEx just
      after the cigarette smoke exposure. We concluded that ET can attenuate the
      aggression from acute smoking to cardiovascular system, with a few days of
      training and even with no chronic effect on these parameters at basal condition. 

PMID- 25575516
TI  - Silencing of MUC8 by siRNA increases P2Y2-induced airway inflammation.
AB  - Mucin hypersecretion and overproduction are frequent manifestations of
      respiratory disease. Determining the physiological function of airway mucin is
      presently considered more important than identifying the relevant signaling
      pathways. The lack of a full-length human mucin 8 (MUC8) cDNA sequence has
      hindered the generation of a Muc8 knockout mouse line. Thus, the precise
      physiological functions of MUC8 are unclear. Herein, we investigated the function
      of MUC8 using a small-interfering RNA (siRNA)-mediated genetic silencing approach
      in human airway epithelial cells. Herein, intracellular IL-1alpha production was
      stimulated by an ATP/P2Y2 complex. While ATP/P2Y2 increased IL-1alpha secretion
      in a time-dependent manner, treatment with P2Y2-specific siRNA significantly
      decreased IL-1alpha secretion. Moreover, ATP increased P2Y2-mediated upregulation
      of MUC8 expression; however, IL-1alpha significantly decreased the extent to
      which ATP/P2Y2 upregulated MUC8 expression. Interestingly, treatment with MUC8
      specific siRNA decreased the production of anti-inflammatory cytokines (TGF-beta
      and IL-1 receptor antagonist) and increased the production of inflammatory
      cytokines (IL-1alpha and IL-6) in our system. In addition, siRNA-mediated
      knockdown of MUC8 expression dramatically increased the secretion of inflammatory
      chemokines and resulted in an approximately threefold decrease in cell
      chemotaxis. We propose that MUC8 may function as an anti-inflammatory mucin that
      participates in inflammatory response by attracting immune cells/cytokines to the
      site of inflammation. Our results provide new insight into the physiological
      function of MUC8 and enhance our understanding of mucin overproduction during
      airway inflammation.

PMID- 25575520
TI  - Effects of garlic oil on interleukin-6 mediated cardiac hypertrophy in
      hypercholesterol-fed hamsters.
AB  - Hypercholesterol diets are the major causes of cardiac hypertrophy and various
      cardiac disorders. The purpose of this study is to evaluate the effects of garlic
      oil on cardiac hypertrophy induced by hypercholesterol diets. Golden Syrian
      hamsters were fed with 2% cholesterol or 2% cholesterol plus 1% garlic oil for 2
      months. Heart architecture changes were measured by hematoxylin-eosin staining
      and the molecular mechanism was determined by western blotting. Garlic oil
      reduced whole-heart weight to bone weight ratio, and left ventricle weight to
      bone weight ratio in the cholesterol-fed group. Moreover, the garlic oil group
      showed significantly reduced interleukin-6, phosphorylated (p)-extracellular
      signal-regulated kinase-5, p-mitogen-activated protein kinase-5, calcineurin,
      nuclear transcription factor of nuclear factor of activated T-cells-3 and p-GATA
      binding protein 4 when compared with the cholesterol group. However, no changes
      were observed in gp-130, signal transducer and activator of transcription-3, p
      P38 and p-Jun N-terminal kinases protein levels in all groups. The results show
      that garlic oil may be useful in the treatment of hypertrophy-associated
      cardiovascular diseases. 

PMID- 25575521
TI  - Upregulated Hsp27 expression in the cardioprotection induced by acute stress and
      oxytocin in ischemic reperfused hearts of the rat.
AB  - In view of the cardioprotective effect of oxytocin (OT) released in response to
      stress, the aim of this study was to evaluate the role of heat shock proteins
      Hsps 70, 27 and 20 in stress-induced cardioprotection in isolated, perfused rat
      hearts. Rats were divided in two main groups: unstressed and stressed rats, and
      all of them were subjected to i.c.v. infusion of vehicle or drugs: unstressed
      rats [control: vehicle, OT (100 ng/5 MUl), atosiban (ATO; 4.3 MUg/5 MUl) as OT
      antagonist, ATO+OT], and stressed rats [St: stress, OT+St, ATO+St]. After
      anesthesia, hearts were isolated and subjected to 30 min regional ischemia and 60
      min subsequent reperfusion (IR). Acute stress protocol included swimming for 10
      min before anesthesia. Malondialdehyde in coronary effluent was measured and the
      expression of Hsp 70, 27 and 20 was measured in myocardium using real-time
      reverse transcriptase polymerase chain reaction (RT-PCR). The malondialdehyde
      levels, which decreased in the St and OT groups, increased by the administration
      of atosiban as an OT antagonist. The expression of Hsp27 increased 4 to 5 folds
      by stress induction and i.c.v. infusion of OT. Central administration of atosiban
      prior to both stress and OT decreased Hsp27 mRNA levels. These findings suggest
      that endogenous OT may participate in stress-induced cardioprotection via Hsp27
      over-expression as an early response. 

PMID- 25575522
TI  - Alteration of cardiac ACE2/Mas expression and cardiac remodelling in rats with
      aortic constriction.
AB  - The recent discovery of the new components of the renin-angiotensin system (RAS)
      suggests the importance of the maintenance of cardiovascular structure and
      functions. To assess the role of the angiotensin-converting enzyme 2 (ACE2)-Mas
      receptor axis in the regulation of cardiac structure and function, the present
      work investigated the expression of ACE2 and Mas receptor in the heart in the
      cardiac remodeling that occurs in aortic constricted rats. Partial abdominal
      aortic ligation was carried out in Sprague-Dawley rats. Angiotensin AT1 receptor
      blockade and ACE inhibition were achieved by losartan and enalapril treatment,
      respectively. Results showed that aortic constriction increased left ventricular
      hypertrophy, fibrosis, mean arterial pressure (MAP), plasma renin activity (PRA)
      and cardiac ACE levels, but decreased the expression of cardiac ACE2 and Mas
      receptor. Losartan treatment significantly decreased MAP, left ventricle
      hypertrophy (LVH), fibrosis, and increased cardiac ACE2 and Mas expression.
      Enalapril also improved the cardiac parameters with a rise in cardiac ACE2, but
      did not change the Mas level. In conclusion, aortic constriction results in
      cardiac hypertrophy, fibrosis and a rise of cardiac ACE expression. Both AT1
      receptor blocker and ACE inhibitor play a cardioprotective role in aortic
      constriction. However, AT1 receptor blocker particularly promotes cardiac ACE2
      and Mas receptor levels. ACE inhibitor is associated with the inhibition of ACE
      and normalization of cardiac ACE2 activity. 

PMID- 25575523
TI  - Inhibition of carotid sinus baroreflex in neonatal rats exposed to chronic
      intermittent hypobaric hypoxia.
AB  - Chronic intermittent hypobaric hypoxia (CIHH) facilitates carotid sinus
      baroreflex (CSB) in adult rats, but the effect of CIHH on CSB in young rats is
      not known. The purpose of present study was to investigate the effect of CIHH on
      CSB in the young rat treated with CIHH from neonatal age, and the role of nitric
      oxide (NO) and Ca2+ in the effect of CIHH. Neonatal male Sprague-Dawley rats were
      randomly divided into three groups: 42-day CIHH treatment group (CIHH42), 56-day
      CIHH treatment group (CIHH56), and an age-matched control group (control). CIHH
      neonatal rats with the maternal rats were exposed to a simulated high-altitude
      hypoxia in a hypobaric chamber mimicking 5,000-m altitude (O2 at 11.1%) for 42 or
      56 days, 6 h per day, respectively. Isolated carotid sinus perfusion technique
      was used to test CSB of the rats. After 42-day and 56-day CIHH exposure, the CSB
      of the rats was inhibited significantly, manifesting as decrease of peak slope
      (PS) and reflex decrease (RD), and increase of threshold pressure (TP),
      equilibrium pressure (EP) and saturation pressure (SP). This inhibitory effect
      was canceled by L-type calcium channel activator Bay K 8644, but not by nitric
      oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The
      data showed that CIHH inhibited CSB in anesthetized young rats through blocking L
      type calcium channels in carotid sinus baroreceptor. 

PMID- 25575524
TI  - Effects of RING-SH2Grb2, a chimeric protein containing the E3 ligase domain of
      Cbl, on the EGFR pathway.
AB  - The E3 ubiquitin-protein ligase Casitas B-lineage lymphoma protein (Cbl)
      negatively regulates epidermal growth factor receptor (EGFR) signaling pathway in
      many organisms, and has crucial roles in cell growth, development and human
      pathologies, including lung cancers. RING-SH2Grb2 a chimeric protein of 215 amino
      acids containing the RING domain of Cbl that provides E3 ligase activity, and the
      SH2 domain of Grb2 that serves as an adaptor for EGFR. In this study, we
      demonstrated that RING-SH2Grb2 could promote the ubiquitinylation and degradation
      of EGFR in a human non-small cell lung carcinoma cell line H1299. Moreover, we
      discovered that the RING-SH2Grb2 chimera promoted the internalization of ligand
      bound EGFR, inhibited the growth of H1299 cells, and significantly suppressed
      tumor growth in a xenograft mouse model. In summary, our results revealed a
      potential new cancer therapeutic approach for non-small cell lung cancer. 

PMID- 25575525
TI  - Manufacturing road map for tissue engineering and regenerative medicine
      technologies.
AB  - The Regenerative Medicine Foundation Annual Conference held on May 6 and 7, 2014,
      had a vision of assisting with translating tissue engineering and regenerative
      medicine (TERM)-based technologies closer to the clinic. This vision was achieved
      by assembling leaders in the field to cover critical areas. Some of these
      critical areas included regulatory pathways for regenerative medicine therapies,
      strategic partnerships, coordination of resources, developing standards for the
      field, government support, priorities for industry, biobanking, and new
      technologies. The final day of this conference featured focused sessions on
      manufacturing, during which expert speakers were invited from industry,
      government, and academia. The speakers identified and accessed roadblocks
      plaguing the field where improvements in advanced manufacturing offered many
      solutions. The manufacturing sessions included (a) product development toward
      commercialization in regenerative medicine, (b) process challenges to scale up
      manufacturing in regenerative medicine, and (c) infrastructure needs for
      manufacturing in regenerative medicine. Subsequent to this, industry was invited
      to participate in a survey to further elucidate the challenges to translation and
      scale-up. This perspective article will cover the lessons learned from these
      manufacturing sessions and early results from the survey. We also outline a road
      map for developing the manufacturing infrastructure, resources, standards,
      capabilities, education, training, and workforce development to realize the
      promise of TERM.

PMID- 25575526
TI  - Concise review: tailoring bioengineered scaffolds for stem cell applications in
      tissue engineering and regenerative medicine.
AB  - The potential for the clinical application of stem cells in tissue regeneration
      is clearly significant. However, this potential has remained largely unrealized
      owing to the persistent challenges in reproducibly, with tight quality criteria,
      and expanding and controlling the fate of stem cells in vitro and in vivo. Tissue
      engineering approaches that rely on reformatting traditional Food and Drug
      Administration-approved biomedical polymers from fixation devices to porous
      scaffolds have been shown to lack the complexity required for in vitro stem cell
      culture models or translation to in vivo applications with high efficacy. This
      realization has spurred the development of advanced mimetic biomaterials and
      scaffolds to increasingly enhance our ability to control the cellular
      microenvironment and, consequently, stem cell fate. New insights into the biology
      of stem cells are expected to eventuate from these advances in material science,
      in particular, from synthetic hydrogels that display physicochemical properties
      reminiscent of the natural cell microenvironment and that can be engineered to
      display or encode essential biological cues. Merging these advanced biomaterials
      with high-throughput methods to systematically, and in an unbiased manner, probe
      the role of scaffold biophysical and biochemical elements on stem cell fate will
      permit the identification of novel key stem cell behavioral effectors, allow
      improved in vitro replication of requisite in vivo niche functions, and,
      ultimately, have a profound impact on our understanding of stem cell biology and
      unlock their clinical potential in tissue engineering and regenerative medicine. 

PMID- 25575527
TI  - Putative immunogenicity expression profiling using human pluripotent stem cells
      and derivatives.
AB  - Autologous human induced pluripotent stem cells (hiPSCs) should allow cellular
      therapeutics without an associated immune response. This concept has been
      controversial since the original report that syngeneic mouse iPSCs elicited an
      immune response after transplantation. However, an investigative analysis of any
      potential acute immune responses in hiPSCs and their derivatives has yet to be
      conducted. In the present study, we used correlative gene expression analysis of
      two putative mouse "immunogenicity" genes, ZG16 and HORMAD1, to assay their human
      homologous expression levels in human pluripotent stem cells and their
      derivatives. We found that ZG16 expression is heterogeneous across multiple human
      embryonic stem cell and hiPSC-derived cell types. Additionally, ectopic
      expression of ZG16 in antigen-presenting cells is insufficient to trigger a
      detectable response in a peripheral blood mononuclear cell coculture assay.
      Neither of the previous immunogenicity-associated genes in the mouse currently
      appears to be relevant in a human context. 

PMID- 25575528
TI  - The psychiatric consequences of physical injury in military personnel: predicting
      and managing the risk.

PMID- 25575529
TI  - The relationship between low-level benzene exposure and blood cell counts in
      Korean workers.
AB  - OBJECTIVES: Benzene is a well-known haematological toxin causing aplastic anaemia
      and leukaemia. Some recent studies have shown that low-level benzene exposure (<1
      ppm) disturbs the haematopoietic system. However, other studies showed
      inconsistent results. The aim of the present study was to examine the
      relationship between low-level benzene exposure and blood cell counts in Korean
      workers. METHODS: Blood cell counts of benzene-exposed workers were extracted
      from a nationwide Special Health Examination Database from 2000 to 2008. If a
      worker did not take a blood test for benzene between 2000 and 2004, the worker
      was selected for analysis. In total, 8679 personal air benzene measurements were
      extracted from the nationwide Workplace Environment Measurement Database from
      2004 to 2008. Mean benzene levels were calculated and assigned to benzene-exposed
      workers using various combinations of factory/industry/process codes. Mixed
      effects models were used to examine dose-related associations between benzene
      levels and white blood cell (WBC), red blood cell (RBC), platelet, neutrophil and
      lymphocyte counts. RESULTS: In total, 21 140 blood samples were tested from 10
      702 workers between 2005 and 2008; 40% of the workers had repeated blood tests
      (average, 3.4 times). RBC counts in male workers showed a significant negative
      association with low-level benzene exposure. WBC, platelet, neutrophil and
      lymphocyte counts did not show a consistent association with low-level benzene
      exposure. CONCLUSIONS: Our findings support the potential haematotoxicity of low
      level benzene exposure (<1 ppm). A longitudinal study with direct benzene
      measurements for exposed workers is needed to confirm the toxicity of low-level
      benzene exposure.

PMID- 25575530
TI  - Varicose veins in the lower extremities in relation to occupational mechanical
      exposures: a longitudinal study.
AB  - OBJECTIVES: To evaluate if occupational mechanical exposures are associated with
      an increased risk of surgery for varicose veins (VV) in the lower extremities.
      METHODS: We conducted a longitudinal study of persons from the Musculoskeletal
      Research Database at the Danish Ramazzini Centre who were 18-65 years old when
      they provided baseline questionnaire data during 1993-2004. Exposure estimates
      were obtained from a job exposure matrix based on expert ratings. The register
      information on first-time surgery for VV was retrieved. We used Cox regression
      analyses. RESULTS: During 416,317 person-years of follow-up among 38,036 persons,
      851 first-time operations for VV occurred. Using standing/walking <4 h/day and
      uncommon lifting as references, exposure-response relationships with risk of
      surgery were found for men. For women, the risk increased too, but without clear
      exposure-response patterns. The adjusted HRs for >=6 h/day spent standing/walking
      were 3.17 (95% CI 2.06 to 4.89) and 2.34 (95% CI 1.72 to 3.19) for men and women,
      respectively. For high lifting exposures (>=1000 kg/day), the adjusted HRs were
      3.95 (95% CI 2.32 to 6.73) for men and 2.54 (95% CI 1.95 to 3.31) for women.
      Other risk factors were increasing age for men and parity for women. Minimal
      leisure-time physical activity, a high body mass index and smoking were not
      associated with increased risk. CONCLUSIONS: The results suggested an increased
      risk of surgery for VV in relation to prolonged standing/walking and heavy
      lifting and a preventive potential of more than 60% of all cases in exposed
      occupations.

PMID- 25575531
TI  - Trends in incidence of occupational asthma, contact dermatitis, noise-induced
      hearing loss, carpal tunnel syndrome and upper limb musculoskeletal disorders in
      European countries from 2000 to 2012.
AB  - OBJECTIVES: The European Union (EU) strategy for health and safety at work
      underlines the need to reduce the incidence of occupational diseases (OD), but
      European statistics to evaluate this common goal are scarce. We aim to estimate
      and compare changes in incidence over time for occupational asthma, contact
      dermatitis, noise-induced hearing loss (NIHL), carpal tunnel syndrome (CTS) and
      upper limb musculoskeletal disorders across 10 European countries. METHODS: OD
      surveillance systems that potentially reflected nationally representative trends
      in incidence within Belgium, the Czech Republic, Finland, France, Italy, the
      Netherlands, Norway, Spain, Switzerland and the UK provided data. Case counts
      were analysed using a negative binomial regression model with year as the main
      covariate. Many systems collected data from networks of 'centres', requiring the
      use of a multilevel negative binomial model. Some models made allowance for
      changes in compensation or reporting rules. RESULTS: Reports of contact
      dermatitis and asthma, conditions with shorter time between exposure to causal
      substances and OD, were consistently declining with only a few exceptions. For OD
      with physical causal exposures there was more variation between countries.
      Reported NIHL was increasing in Belgium, Spain, Switzerland and the Netherlands
      and decreasing elsewhere. Trends in CTS and upper limb musculoskeletal disorders
      varied widely within and between countries. CONCLUSIONS: This is the first direct
      comparison of trends in OD within Europe and is consistent with a positive impact
      of European initiatives addressing exposures relevant to asthma and contact
      dermatitis. Taking a more flexible approach allowed comparisons of surveillance
      data between and within countries without harmonisation of data collection
      methods.

PMID- 25575532
TI  - Enhancement of cancer chemotherapeutic efficacy of cyclophosphamide by Curculigo
      orchioides Gaertn and its ameliorative effects on cyclophosphamide-induced
      oxidative stress.
AB  - Cyclophosphamide (CTX) is a synthetic antineoplastic drug with severe and life
      threatening side effects. Studies in search of protective agents, preferably
      natural products, that can alleviate these side effects are valuable because they
      can contribute to improve current chemotherapeutic treatment strategies.
      Curculigo orchioides Gaertn (family Hypoxidaceae) is well known for its medicinal
      use in the Indian Ayurvedic system of medicine, and various studies have been
      reported that proved its immunomodulatory and anti-inflammatory properties. In
      this study, the tumor reduction capacity of CTX in combination with C orchioides
      methanolic extract was studied using Dalton's lymphoma ascites-induced solid
      tumor models. Effect of C orchioides on the reversal of the damage induced by CTX
      administration (intraperitoneally) was also determined in this study. For this,
      solid tumor volume, serum cytokine levels, hematolological parameters, intestinal
      histopathology, and serum and tissue biochemical parameters (Glutathione [GSH],
      alkaline phosphatase [ALP], glutamate pyruvate transaminase [GPT], lipid
      peroxidation [LPO]) were analyzed. Immune suppression and increased serum
      proinflammatory cytokine levels caused by CTX administration (25 mg/kg body
      weight) were reversed by C orchioides (20 mg/kg body weight). The alcoholic
      extract enhanced the tumor reduction capacity of CTX and reduced GPT and ALP
      levels in liver and serum, which were elevated by CTX administration. The LPO
      level was also lower in the CTX-administered animals when treated with the C
      orchioides extract. In conclusion, the plant extract when administered in
      combination with CTX, can result in enhanced anticancer properties; it also
      ameliorates the toxic side effects of CTX. 

PMID- 25575533
TI  - Percutaneous epicardial access for mapping and ablation is feasible in patients
      with prior cardiac surgery, including coronary bypass surgery.
AB  - BACKGROUND: Prior cardiac surgery, especially the presence of coronary artery
      bypass grafts, is thought to preclude percutaneous epicardial access (EpiAcc)
      and, therefore, mapping and ablation. We evaluated the feasibility and safety of
      EpiAcc in patients with a prior cardiac operation. METHODS AND RESULTS: We
      retrospectively analyzed all patients who underwent EpiAcc for ablation for
      ventricular tachycardia or symptomatic premature ventricular complexes between
      2004 and 2013 at Mayo Clinic, Rochester, MN. Of 162 patients who underwent
      EpiAcc, 18 had prior cardiac surgery (median age, 64 years, all men). This
      included 10 coronary artery bypass grafts, 2 epicardial implantable cardioverter
      defibrillator placement, 5 valve surgery, 2 septal myectomy, 1 aortic arch
      replacement, 1 myocardial bridge unroofing, and 1 myocardial perforation repair
      (3 patients had multiple procedures). Access was successful in 12 of 18; the
      inferior approach was used in 78%. Successful access was achieved in 6 of 10
      patients with prior coronary artery bypass grafts. Adhesiolysis was required in
      10 patients with the sheath, access wire, and pigtail or ablation catheter.
      Intraprocedural coronary angiography was performed in 8 patients. A total of 45
      ventricular tachycardias/premature ventricular complexes were ablated. Thirteen
      patients underwent endocardial-only ablation, 2 had epicardial-only ablation,
      whereas 3 had endocardial-epicardial ablation. Ablation was deemed successful in
      13 of 18 patients. Four patients had bleeding complications (pericardial
      effusion, pericardial hematoma, hemoperitoneum, and pericardial tamponade). In
      patients with coronary grafts, there was no evidence of acute graft disruption.
      CONCLUSIONS: Percutaneous EpiAcc is feasible in patients with previous cardiac
      surgery, including coronary artery bypass grafts. However, adhesiolysis is
      frequently required. Although the risk of coronary graft injury is low, life
      threatening complications may occur.

PMID- 25575535
TI  - Systematic technique-dependent differences in CT versus MRI measurement of the
      tibial tubercle-trochlear groove distance.
AB  - BACKGROUND: The tibial tubercle-trochlear groove (TTTG) distance is used to
      quantify the degree of lateralization of the patellar tendon insertion on the
      tibial tubercle relative to the deepest part of the trochlear groove.
      Disagreement exists as to whether the TTTG distance measured on computed
      tomography (CT) and magnetic resonance imaging (MRI) can be considered
      equivalent. PURPOSE: To compare TTTG distance as measured on axial CT and MRI and
      to investigate the potential effect of patient positioning between modalities.
      STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: Patients
      who received both CT and MRI of the same knee for any indication from August 2010
      to April 2014 were included in this study. The TTTG distances were measured twice
      by 2 raters in a randomized order, with at least 30 days between ratings to
      minimize recall bias. Inter- and intrarater reliability of CT and MRI
      measurements and intermethod reliability were assessed with intraclass
      correlation coefficients (ICCs). Bland-Altman plots were also created to assess
      agreement. Differences in patient positioning were investigated to determine its
      effect on the TTTG distance. RESULTS: Fifty-nine patients (age, 32.8 +/- 12.9
      years) were included. Interrater ICCs were excellent for both CT and MRI
      measurements. Intrarater ICCs were excellent for both raters. Absolute agreement
      ICCs for intermethod reliability were fair to good, but consistency type
      agreement was excellent. A systematic bias of lower MRI distances (bias = -2.8
      mm) compared with CT was observed. The investigation of CT versus MRI imaging
      techniques demonstrated that the standard MRI examination places the knee in
      approximately 4.6 degrees  of relative varus alignment compared with CT.
      CONCLUSION: A systematic bias toward lower TTTG distances on MRI compared with CT
      was found. This finding is likely dependent on imaging technique, including
      patient positioning. Patient knees were positioned in varus on the MRI compared
      with the CT examination, with resulting lower TTTG distances on MRI compared with
      CT. The TTTG distances on CT and MRI vary with imaging technique, which may be
      attributable to patient positioning and result in differences among imaging
      centers.

PMID- 25575534
TI  - Elevated adult neurogenesis in brain subventricular zone following in vivo
      manganese exposure: roles of copper and DMT1.
AB  - The brain subventricular zone (SVZ) is a source of neural precursor cells; these
      cells travel along the rostral migratory stream (RMS) to destination areas in the
      process of adult neurogenesis. Recent x-ray fluorescence (XRF) studies reveal an
      extensive accumulation of copper (Cu) in the SVZ. Earlier human and animal
      studies also suggest an altered Cu homeostasis after manganese (Mn) exposure.
      This study was designed to test the hypothesis that Mn exposure by acting on the
      divalent metal transporter-1 (DMT1) altered Cu levels in SVZ and RMS, thereby
      affecting adult neurogenesis. Adult rats received intraperitoneal (i.p.)
      injections of 6 mg Mn/kg as MnCl2 once daily for 4 weeks with concomitant
      injections of bromodeoxyuridine (BrdU) for 5 days in the last week. In control
      rats, Cu levels were significantly higher in the SVZ than other brain regions
      examined. Mn exposure significantly reduced Cu concentrations in the SVZ (P <
      0.01). Immunohistochemical data showed that in vivo Mn exposure significantly
      increased numbers of BrdU(+) cells, which were accompanied with increased GFAP(+)
      astrocytic stem cells and DCX(+) neuroblasts in SVZ and RMS. Quantitative RT-PCR
      and Western blot confirmed the increased expression of DMT1 in SVZ following in
      vivo Mn exposure, which contributed to Mn accumulation in the neurogenesis
      pathway. Taken together, these results indicate a clear disruptive effect of Mn
      on adult neurogenesis; the effect appears due partly to Mn induction of DMT1 and
      its interference with cellular Cu regulation in SVZ and RMS. The future research
      directions based on these observations are also discussed. 

PMID- 25575536
TI  - Can the site-frequency spectrum distinguish exponential population growth from
      multiple-merger coalescents?
AB  - The ability of the site-frequency spectrum (SFS) to reflect the particularities
      of gene genealogies exhibiting multiple mergers of ancestral lines as opposed to
      those obtained in the presence of population growth is our focus. An excess of
      singletons is a well-known characteristic of both population growth and multiple
      mergers. Other aspects of the SFS, in particular, the weight of the right tail,
      are, however, affected in specific ways by the two model classes. Using an
      approximate likelihood method and minimum-distance statistics, our estimates of
      statistical power indicate that exponential and algebraic growth can indeed be
      distinguished from multiple-merger coalescents, even for moderate sample sizes,
      if the number of segregating sites is high enough. A normalized version of the
      SFS (nSFS) is also used as a summary statistic in an approximate Bayesian
      computation (ABC) approach. The results give further positive evidence as to the
      general eligibility of the SFS to distinguish between the different histories. 

PMID- 25575537
TI  - Genotype-Guided Dosing of Coumarin Anticoagulants: A Meta-analysis of Randomized
      Controlled Trials.
AB  - BACKGROUND: Coumarin anticoagulants (acenocoumarol, phenprocoumon, and warfarin)
      are generally used for the prevention of stroke in patients with atrial
      fibrillation or for the therapy and prevention of venous thromboembolism.
      However, the safe use of coumarin anticoagulants is restricted by a narrow
      therapeutic window and large interindividual dosing variations. Some studies
      found that the effectiveness and safety of coumarin anticoagulants therapy were
      increased by pharmacogenetic-guided dosing algorithms, while others found no
      significant effect of genotype-guided therapy. METHODS: Four electronic databases
      were searched from January 1, 2000, to March 1, 2014, for randomized controlled
      trials of patients who received coumarin anticoagulants according to genotype
      guided dosing algorithms. The primary outcome was the percentage of time that the
      international normalized ratio (INR) was within the normal range (2.0-3.0).
      Secondary outcomes included major bleeding events, thromboembolic events, and INR
      >=4 events. RESULTS: Eight studies satisfied the inclusion and exclusion
      criteria. Genotype-guided dosing of coumarin anticoagulants improved the
      percentage of time within the therapeutic INR range (95% confidence interval
      [CI], 0.02-0.28; P = .02; I(2) = 70%). Subgroup analysis was performed after
      dividing the nongenotype-guided group into a standard-dose group (95% CI, 0.14
      0.49; P = .0004; I(2) = 50%) and a clinical variables-guided dosing algorithm
      group (95% CI, -0.07-0.15; P = .48; I(2) = 34%). There is a statistically
      significant reduction in numbers of secondary outcomes (INR >=4 events, major
      bleeding events, and thromboembolic events; 95% CI, 0.79-1.00; P = .04). Subgroup
      analysis of secondary outcomes showed no significant difference between genotype
      guided dosing and clinical variables-guided dosing (95% CI, 0.84-1.10; P = .57;
      I(2) = 11%), but genotype-guided dosing reduced secondary outcomes compared with
      standard dosing (95% CI, 0.62-0.92; P = .006; I(2) = 0%). CONCLUSIONS: This meta
      analysis showed that genotype-guided dosing increased the effectiveness and
      safety of coumarin therapy compared with standard dosing but did not have
      advantages compared with clinical variables-guided dosing.

PMID- 25575538
TI  - Pomalidomide plus low-dose dexamethasone in multiple myeloma with deletion 17p
      and/or translocation (4;14): IFM 2010-02 trial results.
AB  - The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) can be
      safely administered to patients with end-stage relapsed/refractory multiple
      myeloma (RRMM). However, we observed a shorter median progression-free survival
      (PFS) and overall survival (OS) in these patients when characterized with adverse
      cytogenetics (deletion 17p and translocation [4;14]) in the Intergroupe
      Francophone Myelome (IFM) 2009-02 trial. We then sought to determine whether MM
      with adverse cytogenetics would benefit more from Pom-Dex if exposed earlier in
      the multicenter IFM 2010-02 trial. The intention-to-treat population included 50
      patients, with a median age of 63 years (38% were >=65 years). Interestingly,
      there was a striking difference in time to progression (TTP), duration of
      response, and overall response rate (ORR) according to the presence of del(17p)
      compared with t(4;14) (TTP, 7.3 vs 2.8 months; duration of response, 8.3 vs 2.4
      months; and ORR, 32% vs 15%). OS was prolonged after Pom-Dex, particularly in
      t(4;14), given the short TTP, suggesting that patients were rescued at relapse
      with further lines of therapy. Pom-Dex, a doublet immunomodulatory drug-based
      regimen, is active and well tolerated in adverse cytogenetic patients with early
      RRMM, particularly in those with del(17p), who are characterized by a high and
      rapid development of a refractoriness state and known for their poor prognosis.
      Future studies will determine the underlying mechanisms of Pom-Dex activity in
      del(17p). This trial is registered at www.clinicaltrials.gov as #NCT01745640. 

PMID- 25575539
TI  - Intraperitoneal administration of activated protein C prevents postsurgical
      adhesion band formation.
AB  - Postsurgical peritoneal adhesion bands are the most important causes of
      intestinal obstruction, pelvic pain, and female infertility. In this study, we
      used a mouse model of adhesion and compared the protective effect of activated
      protein C (APC) to that of the Food and Drug Administration-approved antiadhesion
      agent, sodium hyaluronate/carboxymethylcellulose (Seprafilm) by intraperitoneal
      administration of either APC or Seprafilm to experimental animals. Pathological
      adhesion bands were graded on day 7, and peritoneal fluid concentrations of
      tissue plasminogen activator (tPA), d-dimer, thrombin-antithrombin complex, and
      cytokines (IL-1beta, IL-6, interferon-gamma, tumor necrosis factor-alpha,
      transforming growth factor-beta1) were evaluated. Inflammation scores were also
      measured based on histologic data obtained from peritoneal tissues. Relative to
      Seprafilm, intraperitoneal administration of human APC led to significantly
      higher reduction of postsurgical adhesion bands. Moreover, a markedly lower
      inflammation score was obtained in the adhesive tissues of the APC-treated group,
      which correlated with significantly reduced peritoneal concentrations of
      proinflammatory cytokines and an elevated tPA level. Further studies using
      variants of human APC with or without protease-activated receptor 1 (PAR1)
      signaling function and mutant mice deficient for either endothelial protein C
      receptor (EPCR) or PAR1 revealed that the EPCR-dependent signaling activity of
      APC is primarily responsible for its protective activity in this model. These
      results suggest APC has therapeutic potential for preventing postsurgical
      adhesion bands. 

PMID- 25575540
TI  - Programmable 3D silk bone marrow niche for platelet generation ex vivo and
      modeling of megakaryopoiesis pathologies.
AB  - We present a programmable bioengineered 3-dimensional silk-based bone marrow
      niche tissue system that successfully mimics the physiology of human bone marrow
      environment allowing us to manufacture functional human platelets ex vivo. Using
      stem/progenitor cells, megakaryocyte function and platelet generation were
      recorded in response to variations in extracellular matrix components, surface
      topography, stiffness, coculture with endothelial cells, and shear forces.
      Millions of human platelets were produced and showed to be functional based on
      multiple activation tests. Using adult hematopoietic progenitor cells our system
      demonstrated the ability to reproduce key steps of thrombopoiesis, including
      alterations observed in diseased states. A critical feature of the system is the
      use of natural silk protein biomaterial allowing us to leverage its
      biocompatibility, nonthrombogenic features, programmable mechanical properties,
      and surface binding of cytokines, extracellular matrix components, and
      endothelial-derived proteins. This in turn offers new opportunities for the study
      of blood component production ex vivo and provides a superior tissue system for
      the study of pathologic mechanisms of human platelet production.

PMID- 25575542
TI  - Risk assessment in the management of newly diagnosed classical Hodgkin lymphoma.
AB  - Treatment of Hodgkin lymphoma is associated with 2 major types of risk: that the
      treatment may fail to cure the disease or that the treatment will prove
      unacceptably toxic. Careful assessment of the amount of the lymphoma (tumor
      burden), its behavior (extent of invasion or specific organ compromise), and host
      related factors (age; coincident systemic infection; and organ dysfunction,
      especially hematopoietic, cardiac, or pulmonary) is essential to optimize
      outcome. Elaborately assembled prognostic scoring systems, such as the
      International Prognostic Factors Project score, have lost their accuracy and
      value as increasingly effective chemotherapy and supportive care have been
      developed. Identification of specific biomarkers derived from sophisticated
      exploration of Hodgkin lymphoma biology is bringing promise of further
      improvement in targeted therapy in which effectiveness is increased at the same
      time off-target toxicity is diminished. Parallel developments in functional
      imaging are providing additional potential to evaluate the efficacy of treatment
      while it is being delivered, allowing dynamic assessment of risk during
      chemotherapy and adaptation of the therapy in real time. Risk assessment in
      Hodgkin lymphoma is continuously evolving, promising ever greater precision and
      clinical relevance. This article explores the past usefulness and the emerging
      potential of risk assessment for this imminently curable malignancy. 

PMID- 25575541
TI  - A multicenter randomized open-label study of rituximab plus rhTPO vs rituximab in
      corticosteroid-resistant or relapsed ITP.
AB  - This study aimed to compare the efficacy and safety of rituximab (RTX) plus
      recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune
      thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed.
      Recruited patients were randomized at a ratio of 2:1 into 2 groups: the
      combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38).
      Overall response was achieved in 79.2% of patients in the combination group vs
      71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was
      45.4% in the combination group compared with 23.7% in the monotherapy group (P =
      .026). The combination group had significantly shorter time to response (TTR;
      median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4
      90 days) (P < .01). There was no difference between these 2 groups in terms of
      the long-term response (P = .12). Our findings demonstrated that the combination
      of RTX and rhTPO significantly increased the CR rate and shortened TTR compared
      with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP
      but failed to show a beneficial effect on the long-lasting response. This study
      is registered at www.clinicaltrials.gov as #NCT01525836. 

PMID- 25575543
TI  - Ribosomopathies and the paradox of cellular hypo- to hyperproliferation.
AB  - Ribosomopathies are largely congenital diseases linked to defects in ribosomal
      proteins or biogenesis factors. Some of these disorders are characterized by
      hypoproliferative phenotypes such as bone marrow failure and anemia early in
      life, followed by elevated cancer risks later in life. This transition from hypo-
      to hyperproliferation presents an intriguing paradox in the field of hematology
      known as "Dameshek's riddle." Recent cancer sequencing studies also revealed
      somatically acquired mutations and deletions in ribosomal proteins in T-cell
      acute lymphoblastic leukemia and solid tumors, further extending the list of
      ribosomopathies and strengthening the association between ribosomal defects and
      oncogenesis. In this perspective, we summarize and comment on recent findings in
      the field of ribosomopathies. We explain how ribosomopathies may provide clues to
      help explain Dameshek's paradox and highlight some of the open questions and
      challenges in the field. 

PMID- 25575544
TI  - Sequential selection of variables using short permutation procedures and multiple
      adjustments: An application to genomic data.
AB  - This work proposes a sequential methodology for selecting variables in
      classification problems in which the number of predictors is much larger than the
      sample size. The methodology includes a Monte Carlo permutation procedure that
      conditionally tests the null hypothesis of no association among the outcomes and
      the available predictors. In order to improve computing aspects, we propose a new
      parametric distribution, the Truncated and Zero Inflated Gumbel Distribution. The
      final application is to find compact classification models with improved
      performance for genomic data. Results using real data sets show that the proposed
      methodology selects compact models with optimized classification performances.

PMID- 25575545
TI  - Lipid production and mixotrophic growth features of cyanobacterial strains
      isolated from various aquatic sites.
AB  - The present study was conducted to determine the potential of five cyanobacteria
      strains isolated from aquatic zones to induce lipid production. The phylogenetic
      affiliation of the isolates was determined by 16S rRNA gene sequencing. Amongst
      the isolates, an efficient cyanobacterium, Synechococcus sp. HS01 showing maximal
      biomass and lipid productivity, was selected for further studies. In order to
      compare lipid productivity, the HS01 strain was grown in different media to
      screen potential significant culture ingredients and to evaluate mixotrophic
      cultivation. Mixotrophic cultivation of the strain using ostrich oil as a carbon
      source resulted in the best lipid productivity. GC analysis of fatty acid methyl
      esters of the selected cyanobacterial strain grown in media supplemented with
      ostrich oil showed a high content of C16 (palmitoleic acid and palmitic acid) and
      C18 (linoleic acid, oleic acid and linolenic acid) fatty acids of 42.7 and 42.8
      %, respectively. Transmission electron micrographs showed that the HS01 cells
      exhibited an elongated rod-shaped appearance, either isolated, paired, linearly
      connected or in small clusters. According to initial experiments, ostrich oil,
      NaNO3 and NaCl were recognized as potential essential nutrients and selected for
      optimization of media with the goal of maximizing lipid productivity. A culture
      optimization technique using the response surface method demonstrated a maximum
      lipid productivity of 56.5 mg l(-1) day(-1). This value was 2.82-fold higher than
      that for the control, and was achieved in medium containing 1.12 g l(-1) NaNO3, 1
      % (v/v) ostrich oil and 0.09 % (w/v) NaCl.

PMID- 25575546
TI  - Production of the antibiotic FR-008/candicidin in Streptomyces sp. FR-008 is co
      regulated by two regulators, FscRI and FscRIV, from different transcription
      factor families.
AB  - In Streptomyces sp. FR-008, the biosynthetic gene cluster of the polyene
      antibiotic FR-008, also known as candicidin, consists of 21 genes, including four
      regulatory genes, fscRI-fscRIV. Our bioinformatics analyses indicate that FscRI
      has an N-terminal PAS domain, whereas the other three regulators have N-terminal
      AAA domains and are members of the LAL (large ATP-binding regulators of the LuxR
      type) family. Deletion of fscRI abolished the production of FR-008, with
      production restored in the complemented strain, supporting a critical role for
      FscRI in FR-008 biosynthesis. Consistent with these findings, transcription of
      genes involved in the biosynthesis and efflux of FR-008 was greatly downregulated
      in a DeltafscRI mutant. Interestingly, the regulatory gene fscRIV was also
      downregulated in the DeltafscRI mutant. Production of FR-008 was reduced, but not
      abrogated, in an fscRIV deletion mutant, and although structural genes were
      downregulated in DeltafscRIV, the changes were much less dramatic than in
      DeltafscRI, suggesting a stronger regulatory role for FscRI. Remarkably,
      transcription of fscRI was also decreased in DeltafscRIV. Expression of fscRI
      restored antibiotic production in a DeltafscRIV mutant, but not vice versa.
      Putative binding sequences for FscRI were identified upstream of fscRIV and the
      three structural genes fscA, fscB and fscD, which encode large modular polyketide
      synthases. Our findings suggest that fscRI and fscRIV are interregulatory,
      whereas expression of fscRII and fscRIII appears to be independent of fscRI and
      fscRIV. This study demonstrates that the regulation of polyene antibiotic
      synthesis can involve mutually regulated transcriptional activators that belong
      to different families. 

PMID- 25575547
TI  - The anti-inflammatory effects of acetaminophen and N-acetylcysteine through
      suppression of the NLRP3 inflammasome pathway in LPS-challenged piglet
      mononuclear phagocytes.
AB  - Acetaminophen (AAP) and N-acetylcysteine (NAC) have been found to have anti
      inflammatory effects via the TLR-NF-kappaB pathway in LPS-challenged piglets.
      However, the action mechanisms employed by AAP and NAC have yet to be completely
      understood. This study investigated the anti-inflammatory effects and mechanisms
      of AAP and NAC on LPS-induced inflammatory responses via the NLRP3 inflammasome
      pathway in piglet mononuclear phagocytes. The results show that mRNA expression
      levels of IL-1beta, IL-18 and NLRP3, as well as the protein level of cleaved
      caspase-1, are significantly increased after LPS challenge in vitro. LPS
      stimulation did not change ASC and caspase-1 mRNA levels, which were components
      of NLRP3 inflammasome complex. AAP (0.5-1.0 mM) and NAC (0.5-1.0 mM) used
      individually or in combination could down-regulate protein expression of cleaved
      caspase-1 and mRNA expression of IL-1beta, IL-18 and NLRP3. NAC could
      significantly enhance the above inhibition actions of AAP. The combined use of
      AAP plus NAC had better inhibition action on the NLRP3 inflammasome pathway.
      These results indicate that the anti-inflammatory effects of AAP and NAC occur
      via the regulation on mRNA expression of NLRP3 and activation of caspase-1. The
      anti-inflammatory activity of AAP and NAC could be related to the suppression of
      NLRP3 inflammasome pathway under LPS stimulation. 

PMID- 25575548
TI  - Association of Rare Loss-Of-Function Alleles in HAL, Serum Histidine: Levels and
      Incident Coronary Heart Disease.
AB  - BACKGROUND: Histidine is a semiessential amino acid with antioxidant and anti
      inflammatory properties. Few data are available on the associations between
      genetic variants, histidine levels, and incident coronary heart disease (CHD) in
      a population-based sample. METHODS AND RESULTS: By conducting whole exome
      sequencing on 1152 African Americans in the Atherosclerosis Risk in Communities
      (ARIC) study and focusing on loss-of-function (LoF) variants, we identified 3
      novel rare LoF variants in HAL, a gene that encodes histidine ammonia-lyase in
      the first step of histidine catabolism. These LoF variants had large effects on
      blood histidine levels (beta=0.26; P=1.2*10(-13)). The positive association with
      histidine levels was replicated by genotyping an independent sample of 718 ARIC
      African Americans (minor allele frequency=1%; P=1.2*10(-4)). In addition, high
      blood histidine levels were associated with reduced risk of developing incident
      CHD with an average of 21.5 years of follow-up among African Americans (hazard
      ratio=0.18; P=1.9*10(-4)). This finding was validated in an independent sample of
      European Americans from the Framingham Heart Study (FHS) Offspring Cohort.
      However, LoF variants in HAL were not directly significantly associated with
      incident CHD after meta-analyzing results from the CHARGE Consortium.
      CONCLUSIONS: Three LoF mutations in HAL were associated with increased histidine
      levels, which in turn were shown to be inversely related to the risk of CHD among
      both African Americans and European Americans. Future investigations on the
      association between HAL gene variation and CHD are warranted.

PMID- 25575549
TI  - Single-cell-level spatial gene expression in the embryonic neural differentiation
      niche.
AB  - With the rapidly increasing availability of high-throughput in situ hybridization
      images, how to effectively analyze these images at high resolution for global
      patterns and testable hypotheses has become an urgent challenge. Here we
      developed a semi-automated image analysis pipeline to analyze in situ
      hybridization images of E14.5 mouse embryos at single-cell resolution for more
      than 1600 telencephalon-expressed genes from the Eurexpress database. Using this
      pipeline, we derived the spatial gene expression profiles at single-cell
      resolution across the cortical layers to gain insight into the key processes
      occurring during cerebral cortex development. These profiles displayed high
      spatial modularity in gene expression, precisely recapitulated known
      differentiation zones, and uncovered additional unknown transition zones or
      cellular states. In particular, they revealed a distinctive spatial transition
      phase dedicated to chromatin remodeling events during neural differentiation,
      which can be validated by genomic clustering patterns, epigenetic modifications
      switches, and network modules. Our analysis further revealed a role of mitotic
      checkpoints during spatial gene expression state transition. As a novel approach
      to analyzing at the single-cell level the spatial modularity, dynamic trajectory,
      and transient states of gene expression during embryonic neural differentiation
      and to inferring regulatory events, our approach will be useful and applicable in
      many different systems for understanding the dynamic differentiation processes in
      vivo and at high resolution. 

PMID- 25575550
TI  - Evidence of digenic inheritance in Alport syndrome.
AB  - BACKGROUND: Alport syndrome is a clinically heterogeneous, progressive
      nephropathy caused by mutations in collagen IV genes, namely COL4A3 and COL4A4 on
      chromosome 2 and COL4A5 on chromosome X. The wide phenotypic variability and the
      presence of incomplete penetrance suggest that a simple Mendelian model cannot
      completely explain the genetic control of this disease. Therefore, we explored
      the possibility that Alport syndrome is under digenic control. METHODS: Using
      massively parallel sequencing, we identified 11 patients who had pathogenic
      mutations in two collagen IV genes. For each proband, we ascertained the presence
      of the same mutations in up to 12 members of the extended family for a total of
      56 persons studied. RESULTS: Overall, 23 mutations were found. Individuals with
      two pathogenic mutations in different genes had a mean age of renal function
      deterioration intermediate with respect to the autosomal-dominant form and the
      autosomal-recessive one, in line with molecule stoichiometry of the disruption of
      the type IV collagen triple helix. CONCLUSIONS: Segregation analysis indicated
      three possible digenic segregation models: (i) autosomal inheritance with
      mutations on different chromosomes, resembling recessive inheritance (five
      families); (ii) autosomal inheritance with mutations on the same chromosome
      resembling dominant inheritance (two families) and (iii) unlinked autosomal and X
      linked inheritance having a peculiar segregation (four families). This pedigree
      analysis provides evidence for digenic inheritance of Alport syndrome. Clinical
      geneticists and nephrologists should be aware of this possibility in order to
      more accurately assess inheritance probabilities, predict prognosis and identify
      other family members at risk.

PMID- 25575551
TI  - Florida violated federal law by underfunding healthcare for needy children, judge
      rules.

PMID- 25575552
TI  - Delivery of cosmetic covers to persons with transtibial and transfemoral
      amputations in an outpatient prosthetic practice.
AB  - BACKGROUND: Limb loss negatively impacts body image to the extent that functional
      activity and societal participation are affected. Scientific literature is
      lacking on the subject of cosmetic covering for prostheses and the rate of
      cosmetic cover utilization by cover type, gender, amputation level, and type of
      healthcare reimbursement. OBJECTIVES: To describe the delivery of cosmetic covers
      in lower limb prostheses in a sample of people with lower extremity amputation.
      STUDY DESIGN: Cross-sectional design METHODS: Patient records from an outpatient
      practice were reviewed for people who received a transtibial or transfemoral
      prosthesis within a selected 2-year period. RESULTS: A total of 294 records were
      reviewed. Regardless of the amputation level, females were significantly (p <=
      0.05) more likely to receive a cover. Type of insurance did not affect whether or
      not a cover was used, but Medicare reimbursed more pull-up skin covers.
      CONCLUSION: There were differences regarding cosmetic cover delivery based on
      gender, and Medicare reimbursed for more pull-up skin covers at the transtibial
      level than other reimbursors did. This analysis was conducted in a warm, tropical
      geographic region of the United States. Results may differ in other parts of the
      world based on many factors including climate and local views of body image and
      disability. CLINICAL RELEVANCE: Cosmetic covering rates are clinically relevant
      because they provide insight into which gender is utilizing more cosmetic covers.
      Furthermore, it can be determined which type of covers are being utilized with
      greater frequency and which insurance type is providing more coverage for them.

PMID- 25575553
TI  - Headache is often over-investigated and overtreated, US study shows.

PMID- 25575554
TI  - Schistosomiasis presenting in travellers: a 15 year observational study at the
      Hospital for Tropical Diseases, London.
AB  - BACKGROUND: Schistosomiasis in returning travellers is one of the most common
      imported tropical infections with potentially serious complications, which are
      preventable if diagnosed early. METHODS: A review was undertaken of consecutive
      cases of schistosomiasis presenting at the Hospital for Tropical Diseases,
      London, UK from 1997 to 2012. RESULTS: All 1020 schistosomiasis cases were from
      Africa and Schistosoma haematobium was the predominant species in those with
      microscopy confirmed schistosomiasis (74.2%, 204/252). The number of cases of
      imported schistosomiasis is decreasing steadily as a proportion of travellers
      seen. The majority of cases were in travellers originating from non-endemic
      settings (81.8%, 707/864). The most common symptom was of genitourinary
      complaints (22.6%, 230/1020), predominantly haematuria (17.8%, 181/1020); 36.1%
      (368) of cases were asymptomatic. Overall 42% had eosinophilia, and 62% of ova
      positive S. haematobium cases had haematuria on urine dip. Thus, no single
      screening tool was sufficient to identify or rule out schistosomiasis when used
      alone. Serology testing was a more sensitive tool in travellers than in other
      patients (p=0.007). CONCLUSIONS: The prevalence of schistosomiasis in presenting
      travellers is decreasing. The predominant presenting species has shifted from S.
      mansoni to S. haematobium. No single test can reliably diagnose schistosomiasis,
      with eosinophilia and urine dip having low sensitivity. Clinicians need to
      continue to undertake a wide spectrum of diagnostic tests to ensure cases of
      schistosomiasis are not missed.

PMID- 25575555
TI  - Are we nearly there yet? Coverage and compliance of mass drug administration for
      lymphatic filariasis elimination.
AB  - Lymphatic filariasis has been targeted for elimination by 2020, and a threshold
      of 65% coverage of mass drug administration (MDA) has been adopted by the Global
      Programme to Eliminate Lymphatic Filariasis (GPELF). A recent review by Babu and
      Babu of 36 studies of MDA for lymphatic filariasis in India found that coverage,
      defined as receipt of tablets, ranged from 48.8 to 98.8%, while compliance,
      defined as actual ingestion of tablets, was 22% lower on average. Moreover, the
      denominator for these coverage figures is the eligible, rather than total,
      population. By contrast, the 65% threshold, in the original modelling study,
      refers to ingestion of tablets in the total population. This corresponds to
      GPELF's use of 'epidemiological drug coverage' as a trigger for the Transmission
      Assessment Surveys (TAS), which indicate whether to proceed to post-MDA
      surveillance. The existence of less strict definitions of 'coverage' should not
      lead to premature TAS that could impair MDA's sustainability.

PMID- 25575556
TI  - Human physiological benefits of viewing nature: EEG responses to exact and
      statistical fractal patterns.
AB  - Psychological and physiological benefits of viewing nature have been extensively
      studied for some time. More recently it has been suggested that some of these
      positive effects can be explained by nature's fractal properties. Virtually all
      studies on human responses to fractals have used stimuli that represent the
      specific form of fractal geometry found in nature, i.e. statistical fractals, as
      opposed to fractal patterns which repeat exactly at different scales. This raises
      the question of whether human responses like preference and relaxation are being
      driven by fractal geometry in general or by the specific form of fractal geometry
      found in nature. In this study we consider both types of fractals (statistical
      and exact) and morph one type into the other. Based on the Koch curve, nine
      visual stimuli were produced in which curves of three different fractal
      dimensions evolve gradually from an exact to a statistical fractal. The patterns
      were shown for one minute each to thirty-five subjects while qEEG was
      continuously recorded. The results showed that the responses to statistical and
      exact fractals differ, and that the natural form of the fractal is important for
      inducing alpha responses, an indicator of a wakefully relaxed state and
      internalized attention. 

PMID- 25575557
TI  - Pathway to psychological change from the structural stability theory.
AB  - We show that a path not yet considered exists in the parameter space of the cusp
      catastrophe that constitutes a 'target-trajectory,' along which psychological
      change may be achieved in a variety of situations by taking advantage of the
      protagonists' resistance. The parameters Pathogen - the pathogenic agent - and
      Therapy, or Dissent and Remedy, are used depending on whether the theory is
      applied to psychotherapy or conflict, respectively. This proposed target
      trajectory offers: (a) conditions optimised in therapy with regard to the
      intrinsic limitations for the reduction of a patient's pathogenic agent, and in
      conflict with regard to the 'red-lines' of the protagonists, and (b) the benefit
      of a step of rapid decrease in the potential barrier to change. Questions raised
      concern the benefit that a patient may obtain from performing his cognitive task
      in psychotherapy with minimal requirement for the reduction of his pathogen, and
      the role that a step of rapid decrease in a potential barrier may play in
      decision-making, in particular when it comes to end a conflict. The argument is
      developed in detail for psychoanalytic resistance, relying on principles and
      procedures described in numerous texts of psychoanalysis. The theory deals with
      scaling laws - power laws - rather than strict equalities. 

PMID- 25575558
TI  - Recurrent multi-day patterns of intimate partner violence and alcohol intake in
      violent relationships.
AB  - Consistent links exist between male and female alcohol intake and intimate
      partner violence (IPV). However, the nature of the relationship remains unclear.
      This study explores the temporal relationships between violence and heavy alcohol
      intake, looking for multi-day patterns. 200 women with a recent history of
      husband-to-wife abuse from six primary care clinics were asked to complete daily
      assessments using Interactive Verbal Response (IVR) via telephone for 12 weeks.
      To identify recurrent strings of activities, we used orbital decomposition. Multi
      day patterns were found at the 5-, 7- and 9-day levels, but most represented
      extensions of 4-day patterns. Overall, consecutive days of male-perpetrated,
      moderate-severe violence were common. In addition, heavy alcohol intake by the
      husband was underrepresented on days involving verbal abuse only but
      overrepresented in consecutive days of such abuse; husband's alcohol intake
      preceded his verbal abuse and a sequence of husband-perpetrated verbal abuse
      followed by mutual abuse followed by wife-perpetrated verbal abuse was noted. No
      patterns involved heavy alcohol intake by the wife. In conclusion, few patterns
      involved heavy alcohol intake by men and none by women. Although husband's heavy
      alcohol intake may contribute to onset and maintenance of verbal abuse, it plays
      little role in recurrent patterns of physical violence.

PMID- 25575559
TI  - A Dynamical View of High School Attendance: An Assessment of Short-term and Long
      term Dependencies in Five Urban Schools.
AB  - While school attendance is a critical mediator to academic achievement, its time
      dependent characteristics are rarely investigated. To remedy situation, this
      paper reports on the analysis of daily attendance rates in five urban high
      schools over a seven-year period. Traditional time series analyses were conducted
      to estimate short-range and cyclical dependencies in the data. An Autoregressive
      Fractional Integrated Moving Average (ARFIMA) approach was used to address long
      range correlational patterns, and detect signs of self-organized criticality. The
      analysis reveals a strong cyclical pattern (weekly) in all five schools, and
      evidence for self-organized criticality in one of the five. These findings
      illustrate the insufficiency of traditional statistical summary measures to
      characterize the distribution of daily attendance, and they suggest that daily
      attendance is not necessarily the stable and predictable feature of school
      effectiveness it is conventionally assumed to be. While educational practitioners
      can probably attest to the many of the irregularities in attendance patterns as
      well as some of their sources, a systematic description of these temporal aspects
      needs to be included in our assessment of daily attendance behavior to inform
      policy decisions, if only to better align formal research in this area with
      existing local knowledge about those patterns. 

PMID- 25575560
TI  - Fractals and dynamics in art and design.
AB  - Many styles of visual art that build on fractal imagery and chaotic dynamics in
      the creative process have been examined in NDPLS in recent years. This article
      presents a gallery of artwork turned into design that appeared in the promotional
      products of the Society for Chaos Theory in Psychology & Life Sciences. The
      gallery showcases a variety of new imaging styles, including photography, that
      reflect a deepening perspective on nonlinear dynamics and art. The contributing
      artworks in design formats combine to render the verve that transcends the
      boundaries between the artistic and scientific communities. 

PMID- 25575561
TI  - Identification of nonviable genes affecting touch sensitivity in Caenorhabditis
      elegans using neuronally enhanced feeding RNA interference.
AB  - Caenorhabditis elegans senses gentle touch along the body via six touch receptor
      neurons. Although genetic screens and microarray analyses have identified several
      genes needed for touch sensitivity, these methods miss pleiotropic genes that are
      essential for the viability, movement, or fertility of the animals. We used
      neuronally enhanced feeding RNA interference to screen genes that cause lethality
      or paralysis when mutated, and we identified 61 such genes affecting touch
      sensitivity, including five positive controls. We confirmed 18 genes by using
      available alleles, and further studied one of them, tag-170, now renamed txdc-9.
      txdc-9 preferentially affects anterior touch response but is needed for tubulin
      acetylation and microtubule formation in both the anterior and posterior touch
      receptor neurons. Our results indicate that neuronally enhanced feeding RNA
      interference screens complement traditional mutageneses by identifying additional
      nonviable genes needed for specific neuronal functions. 

PMID- 25575563
TI  - Laccases: old enzymes with a promising future.

PMID- 25575562
TI  - New paradigms in the repair of oxidative damage in human genome: mechanisms
      ensuring repair of mutagenic base lesions during replication and involvement of
      accessory proteins.
AB  - Oxidized bases in the mammalian genome, which are invariably mutagenic due to
      their mispairing property, are continuously induced by endogenous reactive oxygen
      species and more abundantly after oxidative stress. Unlike bulky base adducts
      induced by UV and other environmental mutagens in the genome that block
      replicative DNA polymerases, oxidatively damaged bases such as 5-hydroxyuracil,
      produced by oxidative deamination of cytosine in the template strand, do not
      block replicative polymerases and thus need to be repaired prior to replication
      to prevent mutation. Following up our earlier studies, which showed that the Nei
      endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of the five base excision
      repair (BER)-initiating enzymes in mammalian cells, has enhanced expression
      during the S-phase and higher affinity for replication fork-mimicking single
      stranded (ss) DNA substrates, we recently provided direct experimental evidence
      for NEIL1's role in replicating template strand repair. The key requirement for
      this event, which we named as the 'cow-catcher' mechanism of pre-replicative BER,
      is NEIL1's non-productive binding (substrate binding without product formation)
      to the lesion base in ss DNA template to stall DNA synthesis, causing fork
      regression. Repair of the lesion in reannealed duplex is then carried out by
      NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER
      initiating enzymes) also interact with several accessory and non-canonical
      proteins including the heterogeneous nuclear ribonucleoprotein U and Y-box
      binding protein 1 as well as high mobility group box 1 protein, whose precise
      roles in BER are still obscure. In this review, we have discussed the recent
      advances in our understanding of oxidative genome damage repair pathways with
      particular focus on the pre-replicative template strand repair and the role of
      scaffold factors like X-ray repairs cross-complementing protein 1 and poly (ADP
      ribose) polymerase 1 and other accessory proteins guiding distinct BER sub
      pathways. 

PMID- 25575564
TI  - c-kit(+) cells: the tell-tale heart of cardiac regeneration?
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in the
      developed world. Although ongoing therapeutic strategies ameliorate symptoms and
      prolong life for patients with cardiovascular diseases, they do not solve the
      critical issue related to the loss of cardiac tissue. Accordingly,
      stem/progenitor cell therapy has emerged as a paramount approach for cardiac
      repair and regeneration. In this regard, c-kit(+) cells have animated much
      interest and controversy. These cells are self-renewing, clonogenic, and
      multipotent and display a noteworthy potential to differentiate into all
      cardiovascular lineages. However, their functional contribution to cardiomyocyte
      turnover is one of the centrally debated issues concerning their regenerative
      potential. Regardless, plentiful preclinical and clinical studies have been
      conducted which provide evidence for the capacity of c-kit(+) cells to improve
      cardiac function. The purpose of this review is to give a comprehensive,
      impartial, critical description and evaluation of the literature on c-kit(+)
      cells from bench to bedside in order to address their true potential, benefits
      and controversies. 

PMID- 25575565
TI  - Abnormal accumulation of desmin in gastrocnemius myofibers of patients with
      peripheral artery disease: associations with altered myofiber morphology and
      density, mitochondrial dysfunction and impaired limb function.
AB  - Patients with peripheral artery disease (PAD) develop a myopathy in their
      ischemic lower extremities, which is characterized by myofiber degeneration,
      mitochondrial dysfunction and impaired limb function. Desmin, a protein of the
      cytoskeleton, is central to maintenance of the structure, shape and function of
      the myofiber and its organelles, especially the mitochondria, and to translation
      of sarcomere contraction into muscle contraction. In this study, we investigated
      the hypothesis that disruption of the desmin network occurs in gastrocnemius
      myofibers of PAD patients and correlates with altered myofiber morphology,
      mitochondrial dysfunction, and impaired limb function. Using fluorescence
      microscopy, we evaluated desmin organization and quantified myofiber content in
      the gastrocnemius of PAD and control patients. Desmin was highly disorganized in
      PAD but not control muscles and myofiber content was increased significantly in
      PAD compared to control muscles. By qPCR, we found that desmin gene transcripts
      were increased in the gastrocnemius of PAD patients as compared with control
      patients. Increased desmin and desmin gene transcripts in PAD muscles correlated
      with altered myofiber morphology, decreased mitochondrial respiration, reduced
      calf muscle strength and decreased walking performance. In conclusion, our
      studies identified disruption of the desmin system in gastrocnemius myofibers as
      an index of the myopathy and limitation of muscle function in patients with PAD.

PMID- 25575566
TI  - Immunohistochemical detection of FLAG-tagged endogenous proteins in knock-in
      mice.
AB  - With recent advances in immunohistochemical (IHC) techniques,
      immunohistochemistry now plays a more important role in research, especially in
      mouse models where characterization of cellular patterns of protein expression
      has become critical. Even with these recent advances, a paucity of IHC quality
      antibodies for some proteins still exists. To address this, we have developed a
      novel IHC assay that utilizes a commercially available goat anti-DDDDK peptide
      polyclonal antibody on paraffin-embedded tissues from knock-in mice expressing
      proteins of interest tagged with a 3 * FLAG epitope at physiologically relevant
      levels. Focusing on two 3 * FLAG-tagged proteins for which specific antibodies
      were available, USP48 and RIPK3, we were able to validate our anti-DDDDK assay by
      comparing the IHC directed against the actual proteins to the anti-DDDDK IHC
      assay, which recognizes the FLAG epitope. We were also able to detect a third 3 *
      FLAG-tagged protein, BAP1, for which quality reagents were not available. This
      universal IHC method will enable researchers to characterize the expression
      patterns of proteins of interest when specific antibodies are lacking.

PMID- 25575567
TI  - Syndecan-4 is a major syndecan in primary human endothelial cells in vitro,
      modulated by inflammatory stimuli and involved in wound healing.
AB  - Syndecans are important cell surface proteoglycans with many functions; yet, they
      have not been studied to a very large extent in primary human endothelial cells.
      The purpose of this study was to investigate syndecan-4 expression in cultured
      human umbilical vein endothelial cells (HUVECs) and assess its role in
      inflammatory reactions and experimental wound healing. qRT-PCR analysis revealed
      that syndecan-3 and syndecan-4 were highly expressed in HUVECs, whereas the
      expression of syndecan-1 and -2 was low. HUVECs were cultured with the
      inflammatory mediators lipopolysaccharide (LPS) and interleukin 1beta (IL-1beta).
      As a result, syndecan-4 expression showed a rapid and strong increase. Syndecan-1
      and -2 expressions decreased, whereas syndecan-3 was unaffected. Knockdown of
      syndecan-4 using siRNA resulted in changes in cellular morphology and focal
      adhesion sites, delayed wound healing and tube formation, and increased secretion
      of the pro-inflammatory and angiogenic chemokine, CXCL8. These data suggest
      functions for syndecan-4 in inflammatory reactions, wound healing and
      angiogenesis in primary human endothelial cells.

PMID- 25575568
TI  - An innovative method for obtaining consistent images and quantification of
      histochemically stained specimens.
AB  - Obtaining digital images of color brightfield microscopy is an important aspect
      of biomedical research and the clinical practice of diagnostic pathology.
      Although the field of digital pathology has had tremendous advances in whole
      slide imaging systems, little effort has been directed toward standardizing color
      brightfield digital imaging to maintain image-to-image consistency and tonal
      linearity. Using a single camera and microscope to obtain digital images of three
      stains, we show that microscope and camera systems inherently produce image-to
      image variation. Moreover, we demonstrate that post-processing with a widely used
      raster graphics editor software program does not completely correct for session
      to-session inconsistency. We introduce a reliable method for creating consistent
      images with a hardware/software solution (ChromaCalTM; Datacolor Inc., NJ) along
      with its features for creating color standardization, preserving linear tonal
      levels, providing automated white balancing and setting automated brightness to
      consistent levels. The resulting image consistency using this method will also
      streamline mean density and morphometry measurements, as images are easily
      segmented and single thresholds can be used. We suggest that this is a superior
      method for color brightfield imaging, which can be used for quantification and
      can be readily incorporated into workflows.

PMID- 25575570
TI  - Food, immunity, and the microbiome.
AB  - There is increasing evidence that ingested diet-borne components are involved in
      the pathogenesis of disorders such as inflammatory bowel diseases,
      atherosclerosis, and type 2 diabetes. Nutrients can have short- and long-term
      effects in shaping the composition of the microbiota. Western diets (enriched in
      fat, phosphatidylcholine, and L-carnitine) promote inflammation and
      atherosclerosis through specific fatty acids and degradation products such as
      trimethylamine N-oxide. Other dietary factors such as carbazoles or tryptophan
      enriched proteins have anti-inflammatory properties-partly via activation of aryl
      hydrocarbon receptors. The microbiota and its metabolic machinery produce a
      myriad of metabolites that serve as important messengers between the diet,
      microbiota, and host. Short-chain fatty acids affect immune responses and
      epithelial integrity via G-protein-coupled receptors and epigenetic mechanisms.
      By increasing our understanding of interactions between diet, immunity, and the
      microbiota, we might develop food-based approaches to prevent or treat many
      diseases. There now is scientific evidence to support the adage "we are what we
      eat," and this process begins in early life. 

PMID- 25575569
TI  - Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal
      pseudo-obstruction.
AB  - BACKGROUND & AIMS: Chronic intestinal pseudo-obstruction (CIPO) is characterized
      by severe intestinal dysmotility that mimics a mechanical subocclusion with no
      evidence of gut obstruction. We searched for genetic variants associated with
      CIPO to increase our understanding of its pathogenesis and to identify potential
      biomarkers. METHODS: We performed whole-exome sequencing of genomic DNA from
      patients with familial CIPO syndrome. Blood and lymphoblastoid cells were
      collected from patients and controls (individuals without CIPO); levels of
      messenger RNA (mRNA) and proteins were analyzed by quantitative reverse
      transcription polymerase chain reaction, immunoblot, and mobility shift assays.
      Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was
      suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut
      tissues were collected and analyzed. RESULTS: We identified a homozygous mutation
      (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with
      CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients
      with CIPO compared with controls. In zebrafish, suppression of rad21a reduced
      expression of runx1; this phenotype was corrected by injection of human RAD21
      mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino
      zebrafish had delayed intestinal transit and greatly reduced numbers of enteric
      neurons, similar to patients with CIPO. This defect was greater in zebrafish with
      suppressed expression of ret and rad21, indicating their interaction in the
      regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not
      RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed
      expression of APOB, compared with control vector. The gut-specific isoform of
      APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the
      RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut
      biopsy specimens. CONCLUSIONS: Some patients with CIPO carry mutations in RAD21
      that disrupt the ability of its product to regulate genes such as RUNX1 and APOB.
      Reduced expression of rad21 in zebrafish, and dysregulation of these target
      genes, disrupts intestinal transit and the development of enteric neurons.

PMID- 25575571
TI  - Training in interventional endoscopy: current and future state.

PMID- 25575573
TI  - Private company says it can no longer run NHS hospital.

PMID- 25575572
TI  - Nutrients, foods, and colorectal cancer prevention.
AB  - Diet has an important role in the development of colorectal cancer. In the past
      few decades, findings from extensive epidemiologic and experimental
      investigations have linked consumption of several foods and nutrients to the risk
      of colorectal neoplasia. Calcium, fiber, milk, and whole grains have been
      associated with a lower risk of colorectal cancer, and red meat and processed
      meat have been associated with an increased risk. There is substantial evidence
      for the potential chemopreventive effects of vitamin D, folate, fruits, and
      vegetables. Nutrients and foods also may interact, as a dietary pattern, to
      influence colorectal cancer risk. Diet likely influences colorectal
      carcinogenesis through several interacting mechanisms. These include the direct
      effects on immune responsiveness and inflammation, and the indirect effects of
      overnutrition and obesity-risk factors for colorectal cancer. Emerging evidence
      also implicates the gut microbiota as an important effector in the relationship
      between diet and cancer. Dietary modification therefore has the promise of
      reducing colorectal cancer incidence. 

PMID- 25575574
TI  - Liver damage and caspase-dependent apoptosis is related to protein malnutrition
      in mice: effect of methionine.
AB  - This study aimed to determine whether the effects on the mouse liver caused by
      three periods of feeding a protein-free diet for 5 days followed by a normal
      complete diet for 5 days (3PFD-CD) are prevented by a constant methionine supply
      (3PFD+Met-CD). The expressions of carbonic anhydrase III (CAIII), fatty acid
      synthase (FAS), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and glutathione
      S-transferase P1 (GSTP1) were assessed by proteomics and reverse transcriptase
      polymerase chain reactions. The liver redox status was examined by measuring the
      activities of superoxide dismutase (SOD) and catalase (CAT), as well as protein
      carbonylation. Because oxidative stress can result in apoptosis, the activity and
      content of caspase-3, as well as the x-linked inhibitor of the apoptosis protein
      (XIAP) and mitochondrial caspase-independent apoptosis inducing factor (AIF)
      contents were assessed. In addition, the liver histomorphology was examined.
      Compared to the controls fed a normal complete diet throughout, feeding with 3PFD
      CD increased the FAS content, decreased the CAIII content, decreased both the SOD
      and CAT activities, and increased protein carbonylation. It also activated
      caspase-3, decreased the XIAP content, decreased the AIF content, increased the
      number of GSTP1-positive foci and caspase-3-positive cells, and caused fatty
      livers. Conversely, the changes were lessened to varying degrees in mice fed
      3PFD+Met-CD. The present results indicate that a regular Met supply lessens the
      biochemical changes, damage, and caspase-dependent apoptosis provoked by
      recurrent dietary amino acid deprivation in the mouse liver. 

PMID- 25575575
TI  - Ga-68 MAA Perfusion 4D-PET/CT Scanning Allows for Functional Lung Avoidance Using
      Conformal Radiation Therapy Planning.
AB  - BACKGROUND: Ga-68-macroaggregated albumin ((68)Ga-perfusion) positron emission
      tomography/computed tomography (PET/CT) is a novel imaging technique for the
      assessment of functional lung volumes. The purpose of this study was to use this
      imaging technique for functional adaptation of definitive radiotherapy plans in
      patients with non-small cell lung cancer (NSCLC). METHODS: This was a prospective
      clinical trial of patients with NSCLC who received definitive 3-dimensional (3D)
      conformal radiotherapy to 60 Gy in 30 fx and underwent pretreatment respiratory
      gated (4-dimensional [4D]) perfusion PET/CT. The "perfused" lung volume was
      defined as all lung parenchyma taking up radiotracer, and the "well-perfused"
      lung volume was contoured using a visually adapted threshold of 30% maximum
      standardized uptake value (SUV max). Alternate 3D conformal plans were
      subsequently created and optimized to avoid perfused and well-perfused lung
      volumes. Functional dose volumetrics were compared using mean lung dose (MLD), V5
      (volume receiving 5 Gy or more), V10, V20, V30, V40, V50, and V60 parameters.
      RESULTS: Fourteen consecutive patients had alternate radiotherapy plans created
      based on functional lung volumes. When considering the original treatment plan,
      the dose to perfused and well-perfused functional lung volumes was similar to
      that of the conventional anatomical lung volumes with an average MLD of 12.15,
      12.67, and 12.11 Gy, respectively. Plans optimized for well-perfused lung
      improved functional V30, V40, V50, and V60 metrics (all P values <.05). The
      functional MLD of well-perfused lung was improved by a median of 0.86 Gy, P <
      .01. However, plans optimized for perfused lung only showed significant
      improvement in the functional V60 dose parameter (median 1.00%, P = .04) but at a
      detriment of a worse functional V5 (median 3.33%, P = .05). CONCLUSIONS: This
      study demonstrates proof of principle that 4D-perfusion PET/CT may enable
      functional lung avoidance during treatment planning of patients with NSCLC.
      Radiotherapy plans adapted to well-perfused but not perfused functional lung
      volumes allow for reduction in dose to functional lung using 3D conformal
      radiotherapy.

PMID- 25575576
TI  - Quality Assurance of a 50-kV Radiotherapy Unit Using EBT3 GafChromic Film: A
      Feasibility Study.
AB  - PURPOSE: Radiochromic EBT3 film is gaining acceptance as a valuable dosimetry
      system for high-energy photon beams. The advantages of these films over other
      dosimetry systems are low spectral sensitivity and high spatial resolution. The
      aim of this study was to validate EBT3 film as a dosimeter for machine and
      treatment quality assurance (QA) of a 50-kV radiotherapy unit. METHODS AND
      MATERIALS: Absolute and relative doses were acquired using EBT3 GafChromic films
      and compared to a parallel-plate ionization chamber (IC), the standard IC for low
      energy X-rays. EBT3 was also used to evaluate beam profiles and output factors.
      Two films above each other, mimicking the clinical situation of a dosimeter on
      top of the skin, were simultaneously irradiated to evaluate EBT3 as in vivo
      dosimeter. All films were irradiated for 3 minutes, which corresponds with a
      surface dose of 3.25 +/- 0.07 Gy. RESULTS: A fifth-order polynomial function was
      found to be the best fit for the calibration curves. Good agreement between IC
      and EBT3 was found for absolute (0.92% for green and red color channels) and
      relative (1.2% and 1.0% for green and red color channels, respectively)
      dosimetry. Output factors for IC and EBT3 were comparable within 2.04% and 1.02%
      for the green and red color channels, respectively. Flatness and symmetry at the
      surface were within 2%. By applying film as in vivo dosimeter, an absorption of
      4.70% needs to be taken into account with respect to the surface dose.
      CONCLUSION: EBT3 GafChromic film is a feasible and valuable QA and dosimetry tool
      for a 50-kV radiotherapy unit. EBT3 can be used for absolute and relative
      dosimetry, measurement of output factors and beam profiles. In vivo patient
      specific QA can also be performed if one corrects for the dose absorption of the
      film.

PMID- 25575577
TI  - Ways of coping of Chinese caregivers for family members with schizophrenia in two
      metropolitan cities: Guangzhou and Hong Kong, China.
AB  - BACKGROUND: In Chinese societies, family caregivers play an important role in the
      recovery of persons with serious mental illness, such as schizophrenia. While
      family caregivers are often invaluable sources of caregiving in the community, a
      majority of them lack adequate knowledge and support skills to cope with the
      tasks involved. AIMS: This study compares the coping strategies and psychological
      health of caregivers for family members with schizophrenia in two Chinese cities,
      Hong Kong and Guangzhou. METHOD: A total of 109 caregivers, including 39 from
      Hong Kong and 70 from Guangzhou, were recruited from non-governmental mental
      health organizations in the two cities. They were assessed by the Chinese version
      of the Ways of Coping Questionnaire and the General Health Questionnaire.
      RESULTS: While there was no significant difference in the psychological distress
      of the family caregivers in the two locations, the Guangzhou caregivers adopt
      significantly more of the eight coping strategies, namely, confronting coping,
      distancing, self-control, seeking social support, accepting responsibility,
      escape-avoidance, planful problem solving and positive reappraisal, than their
      counterparts in Hong Kong. Significant correlations were also found between
      psychological distress and coping strategies of caregivers in the two cities.
      CONCLUSION: There were significant differences in the coping strategies of family
      caregivers for people with schizophrenia in the two Chinese cities. Further
      studies are warranted to investigate factors affecting their coping strategies
      and their effects on psychological health.

PMID- 25575578
TI  - Role of traditional healers in the pathway to care of patients with bipolar
      disorder in Egypt.
AB  - BACKGROUND: A large number of mentally ill patients prefer to visit non-medical
      practitioners such as traditional healers because of the confidence in the
      system, affordability and accessibility of the service. This may lead to delay in
      seeking psychiatric services and has prognostic impact. AIM: To assess the rate
      of bipolar affective disorder (BAD) patients seeking traditional healers, the
      sociodemographic and clinical correlates of those patients. METHODS: We assessed
      350 patients with BAD after confirmation of diagnosis with Structured Clinical
      Interview for DSM-IV Axis I Disorder (SCID-I) research version and assessment of
      functioning with Global Assessment of Functioning scale. They were assessed for
      percent, rate and timing of seeking traditional healers. RESULTS: In all, 40.8%
      sought traditional healers, with 34.9% more than four times. Of those, 62.2% were
      before seeking psychiatric services and 37.8% after. Lower educational level,
      less impairment of functioning and presence of hallucinations were significant
      correlates. CONCLUSION: This study shows that most of the patients suffering from
      mental illness prefer to approach faith healers first, which may delay entry to
      psychiatric care and thereby negatively impact the prognosis of BAD. This
      highlights the importance of mental health education and developing a positive
      collaborative relationship with traditional healers.

PMID- 25575579
TI  - Survival and neurocognitive outcomes after cardiac extracorporeal life support in
      children less than 5 years of age: a ten-year cohort.
AB  - BACKGROUND: Survival after pediatric cardiac extracorporeal life support (ECLS)
      is guarded, and neurological morbidity varies widely. Our objective is to report
      our 10-year experience with cardiac ECLS, including survival and kindergarten
      entry neurocognitive outcomes; to identify predictors of mortality or adverse
      neurocognitive outcomes; and to compare 2 eras, before and after 2005. METHODS
      AND RESULTS: From 2000 to 2009, 98 children had venoarterial cardiac ECLS. Sixty
      four patients (65%) survived to hospital discharge, and 50 (51%) survived <=5
      years of age. Neurocognitive follow-up of survivors was completed at mean (SD)
      age of 52.9 (8) months using Wechsler Preschool and Primary Scale of
      Intelligence. Logistic regression analysis found the longer time (hours) for
      lactate to fall below 2 mmol/L on ECLS (hazard ratio, 1.39; 95% confidence
      interval, 1.05, 1.84; P=0.022), and the amount of platelets (mL/kg) given in the
      first 48 hours (hazard ratio, 1.18; 95% confidence interval, 1.06, 1.32; P=0.002)
      was independently associated with higher in-hospital mortality. Receiving ECLS
      after the year 2005 was independently associated with lower risk of in-hospital
      mortality (hazard ratio, 0.36; 95% confidence interval, 0.13, 0.99; P=0.048).
      Extracorporeal cardiopulmonary resuscitation was not independently associated
      with mortality or neurocognitive outcomes. Era was not independently associated
      with neurocognitive outcomes. The full-scale intelligence quotient of survivors
      without chromosomal abnormalities was 79.7 (16.6) with 25% below 2 SD of the
      population mean. CONCLUSIONS: Mortality has improved over time; time for lactate
      to fall on ECLS and volume of platelets transfused are independent predictors of
      mortality. Extracorporeal cardiopulmonary resuscitation and era were not
      independently associated with neurocognitive outcomes.

PMID- 25575580
TI  - Association between use of statins and outcomes in heart failure with reduced
      ejection fraction: prospective propensity score matched cohort study of 21 864
      patients in the Swedish Heart Failure Registry.
AB  - BACKGROUND: In heart failure (HF) with reduced ejection fraction, randomized
      trials of statins did not demonstrate improved outcomes. However, randomized
      trials may not always be generalizable. The aim was to determine whether statins
      are associated with improved outcomes in an unselected nationwide population of
      patients with HF with reduced ejection fraction overall and in relation to
      ischemic heart disease (IHD). METHODS AND RESULTS: In the Swedish Heart Failure
      Registry, 21 864 patients with HF with reduced ejection fraction (age +/- SD,
      72+/-12 years; 29% women), of whom 10 345 (47%) were treated with statins, were
      studied. Propensity scores for statin use were derived from 42 baseline
      variables. The associations between statin use and outcomes were assessed with
      Cox regressions in a population matched 1:1 based on propensity score and age and
      in the overall population with adjustment for propensity score and age. The
      primary outcome was all-cause mortality; secondary outcomes were cardiovascular
      mortality; HF hospitalization; and combined all-cause mortality or cardiovascular
      hospitalization. Survival at 1 year in the matched population was 83% for statin
      treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence
      interval, 0.76-0.86; P<0.001). In the unmatched population, 1-year survival was
      85% for statin-treated versus 79% for untreated patients, hazard ratio after
      adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80
      0.89; P<0.001). No examined baseline variables interacted with statin use except
      for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70
      0.82, P<0.001) with IHD and 0.95 (95% confidence interval, 0.85-1.07; P=0.430
      without IHD. Statin use was also associated with reduced risk for all 3 secondary
      outcomes. CONCLUSIONS: In an unselected nationwide population of patients with HF
      with reduced ejection fraction, statins were associated with improved outcomes,
      specifically in the presence of IHD. This contrasts with previous randomized
      controlled trials. Additional randomized controlled trials with more generalized
      inclusion or focused on IHD may be warranted.

PMID- 25575581
TI  - CT findings in a patient with bilateral metachronous carotidynia.
AB  - Carotidynia is a self-limiting, idiopathic clinical syndrome characterized by
      acute unilateral neck pain and tenderness of the carotid artery. We describe a
      unique case of bilateral carotidynia that occurred metachronously, with each
      incident resolving without long-term sequelae. Knowledge of this entity is
      important to properly interpret the imaging findings and to not mistake this
      finding as an ill-defined tumor, thus avoiding unnecessary biopsy. 

PMID- 25575582
TI  - Totally extraperitoneal (TEP) endoscopic inguinal hernia repair with TAP
      (transversus abdominis plane) block as a day-case: a prospective cohort study.
AB  - BACKGROUND: Totally extraperitoneal (TEP) endoscopic inguinal hernia repair is
      indicated for recurrent and bilateral inguinal hernias and traditionally is
      performed under general anesthesia. However, interventions that minimize pain and
      reduce opioid consumption have certain advantages for patients by avoiding side
      effects such as nausea and vomiting. The transversus abdominis plane (TAP) block
      has been used to minimize pain in a diverse range of surgical procedures but its
      safety on patients undergoing TEP repair has yet to be investigated. AIM: To
      assess the results of outpatient TEP repair with TAP block without curare.
      METHODS: Consecutive patients undergoing elective TEP procedure were
      prospectively enrolled. Patients in two institutes received a similar anesthetic,
      surgical, and analgesic treatment protocol. RESULTS: Fifty consecutive day-case
      patients were included in this series. The TEP repair was successful in 49
      patients and there was one conversion to transabdominal pre-peritoneal (TAPP)
      endoscopic inguinal hernia repair. The mean duration of surgery was 20min for
      unilateral hernia and 40min for bilateral hernia. CONCLUSION: These preliminary
      results suggest that day-case endoscopic hernia repair (TEP) with TAP block
      without curare is effective, safe, reproducible and can be proposed in all
      patients.

PMID- 25575583
TI  - Mass spectrometry imaging of biological tissue: an approach for multicenter
      studies.
AB  - Mass spectrometry imaging has become a popular tool for probing the chemical
      complexity of biological surfaces. This led to the development of a wide range of
      instrumentation and preparation protocols. It is thus desirable to evaluate and
      compare the data output from different methodologies and mass spectrometers.
      Here, we present an approach for the comparison of mass spectrometry imaging data
      from different laboratories (often referred to as multicenter studies). This is
      exemplified by the analysis of mouse brain sections in five laboratories in
      Europe and the USA. The instrumentation includes matrix-assisted laser
      desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDI-Fourier
      transform ion cyclotron resonance (FTICR), atmospheric-pressure (AP)-MALDI
      Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental
      parameters such as measurement speed, imaging bin width, and mass spectrometric
      parameters are discussed. All datasets were converted to the standard data format
      imzML and displayed in a common open-source software with identical parameters
      for visualization, which facilitates direct comparison of MS images. The imzML
      conversion also allowed exchange of fully functional MS imaging datasets between
      the different laboratories. The experiments ranged from overview measurements of
      the full mouse brain to detailed analysis of smaller features (depending on
      spatial resolution settings), but common histological features such as the corpus
      callosum were visible in all measurements. High spatial resolution measurements
      of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low
      micrometer range. We discuss general considerations for planning and performing
      multicenter studies in mass spectrometry imaging. This includes details on the
      selection, distribution, and preparation of tissue samples as well as on data
      handling. Such multicenter studies in combination with ongoing activities for
      reporting guidelines, a common data format (imzML) and a public data repository
      can contribute to more reliability and transparency of MS imaging studies. 

PMID- 25575585
TI  - Using feature objects aided strategy to evaluate the biomethane production of
      food waste and corn stalk anaerobic co-digestion.
AB  - Feature objects aided strategy was used to predict and evaluate the biomethane
      production of food waste and corn stalk anaerobic co-digestion. The kinetics of
      co-digestion and mono-digestion of food waste and/or corn stalk was also
      analyzed. The results indicated that the compositions of food waste and corn
      stalk were significantly different. The anaerobic digestion of three feature
      objects at different mixing ratios showed the different biomethane yields and
      kinetic constants. Food waste and corn stalk co-digestion enhanced the digestion
      rate and achieved 22.48% and 41.55% higher biomethane production than those of
      food waste and corn stalk mono-digestion, respectively. 

PMID- 25575584
TI  - Bupropion increases selection of high effort activity in rats tested on a
      progressive ratio/chow feeding choice procedure: implications for treatment of
      effort-related motivational symptoms.
AB  - BACKGROUND: Depression and related disorders are characterized by deficits in
      behavioral activation, exertion of effort, and other psychomotor/motivational
      dysfunctions. Depressed patients show alterations in effort-related decision
      making and a bias towards selection of low effort activities. It has been
      suggested that animal tests of effort-related decision making could be useful as
      models of motivational dysfunctions seen in psychopathology. METHODS: Because
      clinical studies have suggested that inhibition of catecholamine uptake may be a
      useful strategy for treatment of effort-related motivational symptoms, the
      present research assessed the ability of bupropion to increase work output in
      rats responding on a test of effort-related decision-making (ie, a progressive
      ratio/chow feeding choice task). With this task, rats can choose between working
      for a preferred food (high-carbohydrate pellets) by lever pressing on a
      progressive ratio schedule vs obtaining a less preferred laboratory chow that is
      freely available in the chamber. RESULTS: Bupropion (10.0-40.0 mg/kg
      intraperitoneal) significantly increased all measures of progressive ratio lever
      pressing, but decreased chow intake. These effects were greatest in animals with
      low baseline levels of work output on the progressive ratio schedule. Because
      accumbens dopamine is implicated in effort-related processes, the effects of
      bupropion on markers of accumbens dopamine transmission were examined. Bupropion
      elevated extracellular dopamine levels in accumbens core as measured by
      microdialysis and increased phosphorylated dopamine and cyclic-AMP related
      phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent
      with D1 and D2 receptor stimulation. CONCLUSION: The ability of bupropion to
      increase exertion of effort in instrumental behavior may have implications for
      the pathophysiology and treatment of effort-related motivational symptoms in
      humans.

PMID- 25575586
TI  - CQC rates 43 of 50 GP practices good or outstanding in its latest report.

PMID- 25575587
TI  - An international ecological study of adult height in relation to cancer incidence
      for 24 anatomical sites.
AB  - BACKGROUND: Anthropometric indices associated with childhood growth and height
      attained in adulthood, have been associated with an increased incidence of
      certain malignancies. To evaluate the cancer-height relationship, we carried out
      a study using international data, comparing various cancer rates with average
      adult height of women and men in different countries. METHODS: An ecological
      analysis of the relationship between country-specific cancer incidence rates and
      average adult height was conducted for twenty-four anatomical cancer sites. Age
      standardized rates were obtained from GLOBOCAN 2008. Average female (112
      countries) and male (65 countries) heights were sourced and compiled primarily
      from national health surveys. Graphical and weighted regression analysis was
      conducted, taking into account BMI and controlling for the random effect of
      global regions. RESULTS: A significant positive association between a country's
      average adult height and the country's overall cancer rate was observed in both
      men and women. Site-specific cancer incidence for females was positively
      associated with height for most cancers: lung, kidney, colorectum, bladder,
      melanoma, brain and nervous system, breast, non-Hodgkin lymphoma, multiple
      myeloma, corpus uteri, ovary, and leukemia. A significant negative association
      was observed with cancer of the cervix uteri. In males, site-specific cancer
      incidence was positively associated with height for cancers of the brain and
      nervous system, kidney, colorectum, non-Hodgkin lymphoma, multiple myeloma,
      prostate, testicular, lip and oral cavity, and melanoma. CONCLUSION: Incidence of
      cancer was associated with tallness in the majority of anatomical/cancer sites
      investigated. The underlying biological mechanisms are unclear, but may include
      nutrition and early-life exposure to hormones, and may differ by anatomical site.

PMID- 25575588
TI  - Effect of dissolved inorganic carbon on beta-carotene and fatty acid production
      in Dunaliella sp.
AB  - This study aimed to explore the effect of sodium bicarbonate (0-200 mM) on the
      production of beta-carotene and lipid content in Dunaliella salina and Dunaliella
      bardawil. Total carotenoid and chlorophyll content were determined at regular
      intervals by a UV-VIS spectrophotometer. The beta-carotene and lipid contents
      were analyzed using high-performance liquid chromatography (HPLC) and gas
      chromatography coupled with mass spectrometry (GC-MS). The HPLC results revealed
      a twofold increase of beta-carotene in D. salina and D. bardawil cultures grown
      with sodium bicarbonate. Moreover, total fatty acid profiles from GC-MS indicated
      a maximum relative percentage of saturated fatty acids (tetradecanoic acid, 10,13
      diethyl, methyl ester and methyl 16-methyl-heptadecanoate) compared to
      polyunsaturated fatty acids in both algae. Our results indicate that the optimum
      concentration of bicarbonate (100 to 150 mM) was required to stimulate a positive
      effect on beta-carotene production as well as the lipid profile in Dunaliella sp.

PMID- 25575589
TI  - One-step purification and porin transport activity of the major outer membrane
      proteins P2 from Haemophilus influenzae, FomA from Fusobacterium nucleatum and
      PorB from Neisseria meningitidis.
AB  - Bacterial porins are major outer membrane proteins that function as essential
      solute transporters between the bacteria and the extracellular environment.
      Structural features of porins are also recognized by eukaryotic cell receptors
      involved in innate and adaptive immunity. To better investigate the function of
      porins, proper refolding is necessary following purification from inclusion
      bodies [1, 2]. Using a single-step size exclusion chromatographic method, we have
      purified three major porins from pathogenic bacteria, the OmpP2 (P2) from
      Haemophilus influenzae, FomA from Fusobacterium nucleatum and PorB from Neisseria
      meningitidis, at high yield and report their unique solute transport activity
      with size exclusion limit. Furthermore, we have optimized their purification
      method and achieved improvement of their thermostability for facilitating
      functional and structural analyses. 

PMID- 25575590
TI  - Identification of FAH domain-containing protein 1 (FAHD1) as oxaloacetate
      decarboxylase.
AB  - Fumarylacetoacetate hydrolase (FAH) domain-containing proteins occur in both
      prokaryotes and eukaryotes, where they carry out diverse enzymatic reactions,
      probably related to structural differences in their respective FAH domains;
      however, the precise relationship between structure of the FAH domain and the
      associated enzyme function remains elusive. In mammals, three FAH domain
      containing proteins, FAHD1, FAHD2A, and FAHD2B, are known; however, their
      enzymatic function, if any, remains to be demonstrated. In bacteria, oxaloacetate
      is subject to enzymatic decarboxylation; however, oxaloacetate decarboxylases
      (ODx) were so far not identified in eukaryotes. Based on molecular modeling and
      subsequent biochemical investigations, we identified FAHD1 as a eukaryotic ODx
      enzyme. The results presented here indicate that dedicated oxaloacetate
      decarboxylases exist in eukaryotes. 

PMID- 25575591
TI  - Anchoring of protein kinase A by ERM (ezrin-radixin-moesin) proteins is required
      for proper netrin signaling through DCC (deleted in colorectal cancer).
AB  - Netrin-1, acting through its principal receptor DCC (deleted in colorectal
      cancer), serves as an axon guidance cue during neural development and also
      contributes to vascular morphogenesis, epithelial migration, and the pathogenesis
      of some tumors. Several lines of evidence suggest that netrin-DCC signaling can
      regulate and be regulated by the cAMP-dependent protein kinase, PKA, although the
      molecular details of this relationship are poorly understood. Specificity in PKA
      signaling is often achieved through differential subcellular localization of the
      enzyme by interaction with protein kinase A anchoring proteins (AKAPs). Here, we
      show that AKAP function is required for DCC-mediated activation of PKA and
      phosphorylation of cytoskeletal regulatory proteins of the Mena/VASP (vasodilator
      stimulated phosphoprotein) family. Moreover, we show that DCC and PKA physically
      interact and that this association is mediated by the ezrin-radixin-moesin (ERM)
      family of plasma membrane-actin cytoskeleton cross-linking proteins. Silencing of
      ERM protein expression inhibits DCC-PKA interaction, DCC-mediated PKA activation,
      and phosphorylation of Mena/VASP proteins as well as growth cone morphology and
      neurite outgrowth. Finally, although expression of wild-type radixin partially
      rescued growth cone morphology and tropism toward netrin in ERM-knockdown cells,
      expression of an AKAP-deficient mutant of radixin did not fully rescue growth
      cone morphology and switched netrin tropism from attraction to repulsion. These
      data support a model in which ERM-mediated anchoring of PKA activity to DCC is
      required for proper netrin/DCC-mediated signaling. 

PMID- 25575592
TI  - Biochemical characterization and structural analysis of a bifunctional
      cellulase/xylanase from Clostridium thermocellum.
AB  - We expressed an active form of CtCel5E (a bifunctional cellulase/xylanase from
      Clostridium thermocellum), performed biochemical characterization, and determined
      its apo- and ligand-bound crystal structures. From the structures, Asn-93, His
      168, His-169, Asn-208, Trp-347, and Asn-349 were shown to provide hydrogen
      bonding/hydrophobic interactions with both ligands. Compared with the structures
      of TmCel5A, a bifunctional cellulase/mannanase homolog from Thermotoga maritima,
      a flexible loop region in CtCel5E is the key for discriminating substrates.
      Moreover, site-directed mutagenesis data confirmed that His-168 is essential for
      xylanase activity, and His-169 is more important for xylanase activity, whereas
      Asn-93, Asn-208, Tyr-270, Trp-347, and Asn-349 are critical for both activities.
      In contrast, F267A improves enzyme activities. 

PMID- 25575593
TI  - Differential effect of plant lipids on membrane organization: specificities of
      phytosphingolipids and phytosterols.
AB  - The high diversity of the plant lipid mixture raises the question of their
      respective involvement in the definition of membrane organization. This is
      particularly the case for plant plasma membrane, which is enriched in specific
      lipids, such as free and conjugated forms of phytosterols and typical
      phytosphingolipids, such as glycosylinositolphosphoceramides. This question was
      here addressed extensively by characterizing the order level of membrane from
      vesicles prepared using various plant lipid mixtures and labeled with an
      environment-sensitive probe. Fluorescence spectroscopy experiments showed that
      among major phytosterols, campesterol exhibits a stronger ability than beta
      sitosterol and stigmasterol to order model membranes. Multispectral confocal
      microscopy, allowing spatial analysis of membrane organization, demonstrated
      accordingly the strong ability of campesterol to promote ordered domain formation
      and to organize their spatial distribution at the membrane surface. Conjugated
      sterol forms, alone and in synergy with free sterols, exhibit a striking ability
      to order membrane. Plant sphingolipids, particularly
      glycosylinositolphosphoceramides, enhanced the sterol-induced ordering effect,
      emphasizing the formation and increasing the size of sterol-dependent ordered
      domains. Altogether, our results support a differential involvement of free and
      conjugated phytosterols in the formation of ordered domains and suggest that the
      diversity of plant lipids, allowing various local combinations of lipid species,
      could be a major contributor to membrane organization in particular through the
      formation of sphingolipid-sterol interacting domains. 

PMID- 25575594
TI  - Cross-talk between two nucleotide-signaling pathways in Staphylococcus aureus.
AB  - Nucleotide-signaling pathways are found in all kingdoms of life and are utilized
      to coordinate a rapid response to external stimuli. The stringent response
      alarmones guanosine tetra- (ppGpp) and pentaphosphate (pppGpp) control a global
      response allowing cells to adapt to starvation conditions such as amino acid
      depletion. One more recently discovered signaling nucleotide is the secondary
      messenger cyclic diadenosine monophosphate (c-di-AMP). Here, we demonstrate that
      this signaling nucleotide is essential for the growth of Staphylococcus aureus,
      and its increased production during late growth phases indicates that c-di-AMP
      controls processes that are important for the survival of cells in stationary
      phase. By examining the transcriptional profile of cells with high levels of c-di
      AMP, we reveal a significant overlap with a stringent response transcription
      signature. Examination of the intracellular nucleotide levels under stress
      conditions provides further evidence that high levels of c-di-AMP lead to an
      activation of the stringent response through a RelA/SpoT homologue (RSH) enzyme
      dependent increase in the (p)ppGpp levels. This activation is shown to be
      indirect as c-di-AMP does not interact directly with the RSH protein. Our data
      extend this interconnection further by showing that the S. aureus c-di-AMP
      phosphodiesterase enzyme GdpP is inhibited in a dose-dependent manner by ppGpp,
      which itself is not a substrate for this enzyme. Altogether, these findings add a
      new layer of complexity to our understanding of nucleotide signaling in bacteria
      as they highlight intricate interconnections between different nucleotide
      signaling networks. 

PMID- 25575595
TI  - Characterization of the pivotal carbon metabolism of Streptococcus suis serotype
      2 under ex vivo and chemically defined in vitro conditions by isotopologue
      profiling.
AB  - Streptococcus suis is a neglected zoonotic pathogen that has to adapt to the
      nutritional requirements in the different host niches encountered during
      infection and establishment of invasive diseases. To dissect the central
      metabolic activity of S. suis under different conditions of nutrient
      availability, we performed labeling experiments starting from [(13)C]glucose
      specimens and analyzed the resulting isotopologue patterns in amino acids of S.
      suis grown under in vitro and ex vivo conditions. In combination with classical
      growth experiments, we found that S. suis is auxotrophic for Arg, Gln/Glu, His,
      Leu, and Trp in chemically defined medium. De novo biosynthesis was shown for
      Ala, Asp, Ser, and Thr at high rates and for Gly, Lys, Phe, Tyr, and Val at
      moderate or low rates, respectively. Glucose degradation occurred mainly by
      glycolysis and to a minor extent by the pentose phosphate pathway. Furthermore,
      the exclusive formation of oxaloacetate by phosphoenolpyruvate (PEP)
      carboxylation became evident from the patterns in de novo synthesized amino
      acids. Labeling experiments with S. suis grown ex vivo in blood or cerebrospinal
      fluid reflected the metabolic adaptation to these host niches with different
      nutrient availability; however, similar key metabolic activities were identified
      under these conditions. This points at the robustness of the core metabolic
      pathways in S. suis during the infection process. The crucial role of PEP
      carboxylation for growth of S. suis in the host was supported by experiments with
      a PEP carboxylase-deficient mutant strain in blood and cerebrospinal fluid. 

PMID- 25575596
TI  - Septin dynamics are essential for exocytosis.
AB  - Septins are a family of 14 cytoskeletal proteins that dynamically form hetero
      oligomers and organize membrane microdomains for protein complexes. The
      previously reported interactions with SNARE proteins suggested the involvement of
      septins in exocytosis. However, the contradictory results of up- or down
      regulation of septin-5 in various cells and mouse models or septin-4 in mice
      suggested either an inhibitory or a stimulatory role for these septins in
      exocytosis. The involvement of the ubiquitously expressed septin-2 or general
      septin polymerization in exocytosis has not been explored to date. Here, by nano
      LC with tandem MS and immunoblot analyses of the septin-2 interactome in mouse
      brain, we identified not only SNARE proteins but also Munc-18-1 (stabilizes
      assembled SNARE complexes), N-ethylmaleimide-sensitive factor (NSF) (disassembles
      SNARE complexes after each membrane fusion event), and the chaperones Hsc70 and
      synucleins (maintain functional conformation of SNARE proteins after complex
      disassembly). Importantly, alpha-soluble NSF attachment protein (SNAP), the
      adaptor protein that mediates NSF binding to the SNARE complex, did not interact
      with septin-2, indicating that septins undergo reorganization during each
      exocytosis cycle. Partial depletion of septin-2 by siRNA or impairment of septin
      dynamics by forchlorfenuron inhibited constitutive and stimulated exocytosis of
      secreted and transmembrane proteins in various cell types. Forchlorfenuron
      impaired the interaction between SNAP-25 and its chaperone Hsc70, decreasing SNAP
      25 levels in cultured neuroendocrine cells, and inhibited both spontaneous and
      stimulated acetylcholine secretion in mouse motor neurons. The results
      demonstrate a stimulatory role of septin-2 and the dynamic reorganization of
      septin oligomers in exocytosis. 

PMID- 25575597
TI  - Erythromelalgia mutation Q875E Stabilizes the activated state of sodium channel
      Nav1.7.
AB  - The human voltage-gated sodium channel Nav1.7 plays a crucial role in
      transmission of noxious stimuli. The inherited pain disorder erythromelalgia
      (IEM) has been linked to Nav1.7 gain-of-function mutations. Here we show that the
      IEM-associated Q875E mutation located on the pore module of Nav1.7 produces a
      large hyperpolarizing shift (-18 mV) in the voltage dependence of activation.
      Three-dimensional homology modeling indicates that the side chains of Gln-875 and
      the gating charge Arg-214 of the domain I voltage sensor are spatially close in
      the activated conformation of the channel. We verified this proximity by using an
      engineered disulfide bridge approach. The Q875E mutation introduces a negative
      charge that may modify the local electrical field experienced by the voltage
      sensor and, upon activation, interact directly via a salt bridge with the Arg-214
      gating charge residue. Together these processes could promote transition to, and
      stabilization of, the domain I voltage sensor in the activated conformation and
      thus produce the observed gain of function. In support of this hypothesis, an
      increase in the extracellular concentration of Ca(2+) or Mg(2+) reverted the
      voltage dependence of activation of the IEM mutant to near WT values, suggesting
      a cation-mediated electrostatic screening of the proposed interaction between
      Q875E and Arg-214. 

PMID- 25575598
TI  - Adiponectin reduces hepatic stellate cell migration by promoting tissue inhibitor
      of metalloproteinase-1 (TIMP-1) secretion.
AB  - Hepatic stellate cells (HSC) are central players in liver fibrosis that when
      activated, proliferate, migrate to sites of liver injury, and secrete
      extracellular matrix. Obesity, a known risk factor for liver fibrosis is
      associated with reduced levels of adiponectin, a protein that inhibits liver
      fibrosis in vivo and limits HSC proliferation and migration in vitro. Adiponectin
      mediated activation of adenosine monophosphate-activated kinase (AMPK) inhibits
      HSC proliferation, but the mechanism by which it limits HSC migration to sites of
      injury is unknown. Here we sought to elucidate how adiponectin regulates HSC
      motility. Primary rat HSCs were isolated and treated with adiponectin in
      migration assays. The in vivo actions of adiponectin were examined by treating
      mice with carbon tetrachloride for 12 weeks and then injecting them with
      adiponectin. Cell and tissue samples were collected and analyzed for gene
      expression, signaling, and histology. Serum from patients with liver fibrosis was
      examined for adiponectin and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      protein. Adiponectin administration into mice increased TIMP-1 gene and protein
      expression. In cultured HSCs, adiponectin promoted TIMP-1 expression and through
      binding of TIMP-1 to the CD63/beta1-integrin complex reduced phosphorylation of
      focal adhesion kinase to limit HSC migration. In mice with liver fibrosis,
      adiponectin had similar effects and limited focal adhesion kinase
      phosphorylation. Finally, in patients with advanced fibrosis, there was a
      positive correlation between serum adiponectin and TIMP-1 levels. In sum, these
      data show that adiponectin stimulates TIMP-1 secretion by HSCs to retard their
      migration and contributes to the anti-fibrotic effects of adiponectin. 

PMID- 25575600
TI  - How does lipid lowering prevent coronary events? New insights from human imaging
      trials.

PMID- 25575601
TI  - The year in cardiology: heart failure 2014.

PMID- 25575602
TI  - Islamic Values and Nursing Practice in Kuwait.
AB  - PURPOSE: This qualitative study sought to illuminate the perception among Muslim
      nurses in Kuwait of the role of Islamic values on their nursing practice. DESIGN:
      Ethnography, specifically Leininger's small scale ethnonursing design, guided the
      study. METHOD: Eighteen male and female Muslim nurses from five countries, who
      were working as nurses in Kuwait, were interviewed. The interviews were
      transcribed and examined for themes. FINDINGS: Seven themes emerged (1)
      altruistic relationships as a core value; (2) all care as spiritual care; (3)
      desire for greater understanding and respect as nurses and as Muslims; (4)
      professional kinship that transcends culture, religion, and nationality; (5)
      nursing ethics from divine ethics; (6) religious teachings promoting health; (7)
      radical acceptance of God's will, balanced with hope of reward. CONCLUSIONS: The
      centrality of the value altruism to nursing care from the Islamic perspective and
      the apparent seamless integration of care of the spirit with care of the body
      were significant findings consistent with the literature. The deep longing to be
      better understood, both as nurses and as Muslims, speaks to needed public
      education across the spectrum of religious belief and needed strengthening of
      professional kinship.

PMID- 25575599
TI  - Personalized contact strategies and predictors of time to survey completion:
      analysis of two sequential randomized trials.
AB  - BACKGROUND: Effective strategies for contacting and recruiting study participants
      are critical in conducting clinical research. In this study, we conducted two
      sequential randomized controlled trials of mail- and telephone-based strategies
      for contacting and recruiting participants, and evaluated participant-related
      variables' association with time to survey completion and survey completion
      rates. Subjects eligible for this study were survivors of acute lung injury who
      had been previously enrolled in a 12-month observational follow-up study
      evaluating their physical, cognitive and mental health outcomes, with their last
      study visit completed at a median of 34 months previously. METHODS: Eligible
      subjects were contacted to complete a new research survey as part of two
      randomized trials, initially using a randomized mail-based contact strategy,
      followed by a randomized telephone-based contact strategy for non-responders to
      the mail strategy. Both strategies focused on using either a personalized versus
      a generic approach. In addition, 18 potentially relevant subject-related
      variables (e.g., demographics, last known physical and mental health status) were
      evaluated for association with time to survey completion. RESULTS: Of 308
      eligible subjects, 67% completed the survey with a median (IQR) of 3 (2, 5)
      contact attempts required. There was no significant difference in the time to
      survey completion for either randomized trial of mail- or phone-based contact
      strategy. Among all subject-related variables, age <=40 years and minority race
      were independently associated with a longer time to survey completion.
      CONCLUSION: We found that age <=40 years and minority race were associated with a
      longer time to survey completion, but personalized versus generic approaches to
      mail- and telephone-based contact strategies had no significant effect. Repeating
      both mail and telephone contact attempts was important for increasing survey
      completion rate. TRIAL REGISTRATION: NCT00719446.

PMID- 25575603
TI  - Usher syndrome: an effective sequencing approach to establish a genetic and
      clinical diagnosis.
AB  - Usher syndrome is an autosomal recessive disorder characterized by retinitis
      pigmentosa, sensorineural hearing loss and, in some cases, vestibular
      dysfunction. The disorder is clinically and genetically heterogeneous and, to
      date, mutations in 11 genes have been described. This finding makes difficult to
      get a precise molecular diagnosis and offer patients accurate genetic
      counselling. To overcome this problem and to increase our knowledge of the
      molecular basis of Usher syndrome, we designed a targeted resequencing custom
      panel. In a first validation step a series of 16 Italian patients with known
      molecular diagnosis were analysed and 31 out of 32 alleles were detected (97% of
      accuracy). After this step, 31 patients without a molecular diagnosis were
      enrolled in the study. Three out of them with an uncertain Usher diagnosis were
      excluded. One causative allele was detected in 24 out 28 patients (86%) while the
      presence of both causative alleles characterized 19 patients out 28 (68%).
      Sixteen novel and 27 known alleles were found in the following genes: USH2A
      (50%), MYO7A (7%), CDH23 (11%), PCDH15 (7%) and USH1G (2%). Overall, on the 44
      patients the protocol was able to characterize 74 alleles out of 88 (84%). These
      results suggest that our panel is an effective approach for the genetic diagnosis
      of Usher syndrome leading to: 1) an accurate molecular diagnosis, 2) better
      genetic counselling, 3) more precise molecular epidemiology data fundamental for
      future interventional plans. 

PMID- 25575604
TI  - Cochlear implant users move in time to the beat of drum music.
AB  - Cochlear implant users show a profile of residual, yet poorly understood, musical
      abilities. An ability that has received little to no attention in this population
      is entrainment to a musical beat. We show for the first time that a heterogeneous
      group of cochlear implant users is able to find the beat and move their bodies in
      time to Latin Merengue music, especially when the music is presented in unpitched
      drum tones. These findings not only reveal a hidden capacity for feeling musical
      rhythm through the body in the deaf and hearing impaired population, but
      illuminate promising avenues for designing early childhood musical training that
      can engage implanted children in social musical activities with benefits
      potentially extending to non-musical domains. 

PMID- 25575605
TI  - DNA methylation regulates bromodomain-containing protein 2 expression during
      adipocyte differentiation.
AB  - Obesity is characterized by excessive accumulation of white adipose tissue.
      Bromodomain-containing protein 2 (Brd2), which belongs to the bromodomain and
      extraterminal domain family of proteins, suppresses adipocyte differentiation.
      DNA methylation is critical for several differentiation processes and possibly in
      adipocyte differentiation. However, whether DNA methylation regulates the
      expression of Brd2 is not clear. In our study, we demonstrated that DNA
      methylation contributes to the regulation of Brd2 expression during pre-adipocyte
      differentiation. Brd2 mRNA levels were low in pre-adipocytes, increased in early
      adipocytes, and declined in mature adipocytes. To test whether and how Brd2
      expression is regulated by DNA methylation during the differentiation of 3T3-L1
      pre-adipocytes to adipocytes, cells were cultured in the presence of the
      methylation inhibitor 5-aza-2'-deoxycytidine (5-Aza). Pre-adipocytes and
      adipocytes exposed to 5-Aza exhibited a dose-dependent increase in Brd2
      transcription levels, while only mature adipocytes exhibited increased expression
      of Brd2 protein. Subsequently, we tested the DNA methylation status of the Brd2
      promoter region. Bisulfite-sequencing analysis revealed that six CpG sites in two
      predicted promoters of Brd2 were demethylated in early adipocytes and highly
      methylated in mature adipocytes. Digestion of bisulfite-converted PCR products of
      the Brd2 promoter region from 3T3-L1 cells with BstU1 (CGGC) revealed that the
      demethylation rate of the Brd2 promoter was consistent with Brd2 mRNA expression
      in differentiating 3T3-L1 cells. In conclusion, DNA demethylation of the Brd2
      promoter region induced Brd2 expression during differentiation of 3T3-L1 cells
      into adipocytes. 

PMID- 25575606
TI  - MiR-214 regulates the pathogenesis of patients with coronary artery disease by
      targeting VEGF.
AB  - Circulating microRNAs (miRNAs) in patient body fluids have recently been
      considered to hold the potential of being novel disease biomarkers and drug
      targets. We aimed to investigate the correlation between the levels of
      circulating miR-214 and the expression of vascular endothelial growth factor
      (VEGF) in the pathogenesis of coronary heart disease patients to further explore
      the mechanism involved in the vasculogenesis. Three different cohorts, including
      13 acute myocardial infarction patients, 176 angina pectoris patients, and 127
      control subjects, were enrolled to investigate the expression levels of
      circulating miR-214 in patients with myocardial ischemia and also the
      relationship between plasma miR-214 and severity of coronary stenosis. Plasma miR
      214 levels of participants were examined by real-time quantitative PCR.
      Simultaneously, plasma cardiac troponin I concentrations were measured by ELISA
      assays. We further detected the correlation of miR-214 and VEGF by molecular and
      animal assays. MiR-214 was enriched in not only diseased endothelial progenitor
      cells (EPCs) but also the plasma of coronary artery disease (CAD) patients.
      Besides, we found out miR-214 was able to suppress VEGF expression and EPC
      activities. Reporter assays confirmed the direct binding and repression of miR
      214 to the 39-UTR of VEGF mRNA. Knockdown of miR-214 not only restored VEGF
      levels and angiogenic activities of diseased EPCs in vitro, but also further
      promoted blood flow recovery in ischemic limbs of mice. Circulating miR-214 may
      be a new biomarker for CAD and as a potential diagnostic tool. And increased miR
      214 level may be used to predict the presence and severity of coronary lesions in
      CAD patients. 

PMID- 25575607
TI  - Reticulated platelets and antiplatelet therapy response in diabetic patients.
AB  - Increased platelet turnover and high level of reticulated platelets are
      associated with low response to antiplatelet therapy in diabetes mellitus type 2.
      This study evaluated association between percentage of reticulated platelets
      (%RP) and the response to antiplatelet therapy in patients with type 2 diabetes
      mellitus (T2DM). This prospective, pilot, case-control, clinical trial included
      79 subjects stratified in three groups: group I included 30 patients with T2DM,
      group II included 34 non-diabetic patients and 15 healthy age and sex matched
      healthy volunteers were enrolled in control group. Platelet response to
      clopidogrel and aspirin was assessed by Multiplate((r)) aggregometry analyzer.
      Individual response to dual antiplatelet therapy was estimated by the percentage
      of decrease in overall platelet aggregability (%DPA) obtained after antiplatelet
      therapy, calculated by presented formulas: %DPAadp = 100 * (1 - ADP/TRAP) and
      %DPAaspi = 100 * (1 - ASPI/TRAP). %RP was significantly higher in diabetics, than
      in non-diabetics, (3.17 +/- 1.26 vs. 2.39 +/- 1.56; p < 0.05). Significantly
      lower response to clopidogrel (31.55 +/- 13.02 vs. 50.24 +/- 11.38; p < 0.001)
      and aspirin (52.33 +/- 22.67 vs. 64.31 +/- 16.47; p < 0.05) therapy was observed
      in diabetics. %RP negatively correlated with response to clopidogrel therapy, but
      positively with metabolic profile indicators in diabetics (p < 0.05, all).
      Correlation of %RP with metabolic profile indicators and poor response to
      antiplatelet therapy suggest that altered metabolic profile can affect platelet
      turnover in T2DM leading to low responsiveness to antiplatelet therapy in these
      patients.

PMID- 25575608
TI  - [Polynesian adaptation of the Mini-Mental State Examination].
AB  - This study aimed to develop and validate a Polynesian version of the MMSE (Mini
      Mental State Examination). For this study a sample (n=112) of healthy people were
      evaluated with the French version of the consensual version of the MMSE, to
      target and modify some inadequate items for French Polynesia. Subsequently, a
      second sample (n=112) with the same characteristics (age, educational level) as
      well as 46 healthy people aged 60 years and more were evaluated with the adaptive
      version of the MMSE (P-MMSE). This version was then applied to 17 participants
      with Alzheimer disease. The control subjects were selected according to their age
      and educational level. The variables gender and evaluation sites were checked. An
      analysis of the results showed a significant dissociation between the two
      versions as well as a meaningful effect on global performance of the variables
      age (r=-0.45) and educational level (r=-0.25). Cut-off scores taking into
      consideration these variables were defined. The sensitivity and specificity
      values of the new cut-off scores were much greater than 0.5. Various global cut
      off scores were also analyzed. A general cut-off score (<=23) was defined and
      yielded 82 % sensitivity and 75 % specificity in detecting Alzheimer disease. 

PMID- 25575609
TI  - [Withdrawal of artificial nutrition and hydration in severe stroke: medical,
      legal and ethical considerations].
AB  - In the majority of cases, severe stroke is accompanied by difficulty in
      swallowing and an altered state of consciousness requiring artificial nutrition
      and hydration. Because of their artificial nature, nutrition and hydration are
      considered by law as treatment rather basic care. Withdrawal of these treatments
      is dictated by the refusal of unreasonable obstinacy enshrined in law and is
      justified by the risk of severe disability and very poor quality of life. It is
      usually the last among other withholding and withdrawal decisions which have
      already been made during the long course of the disease. Reaching a collegial
      consensus on a controversial decision such as artificial nutrition and hydration
      withdrawal is a difficult and complex process. The reluctance for such decisions
      is mainly due to the symbolic value of food and hydration, to the fear of "dying
      badly" while suffering from hunger and thirst, and to the difficult distinction
      between this medical act and euthanasia. The only way to overcome such reluctance
      is to ensure flawless accompaniment, associating sedation and appropriate comfort
      care with a clear explanation (with relatives but also caregivers) of the
      rationale and implications of this type of decision. All teams dealing with this
      type of situation must have thoroughly thought through the medical, legal and
      ethical considerations involved in making this difficult decision. 

PMID- 25575610
TI  - [Follow-up of a cohort of patients after substitution of phenytoin for phenytoin
      sodium in an epilepsy center].
AB  - In March 2012, the French Health Products Safety Agency interrupted the
      commercialization of di-hydan (phenytoin). It was replaced by diphantoine
      (phenytoin sodium) and prescribers were informed that posology was equivalent for
      both products. We conducted a retrospective study of phenytoinemia and clinical
      effects comparatively for these two drugs in a population of adult patients with
      epilepsy admitted in La TEPPE. Forty-four patients were included. Mean age was
      47.6 years. Phenytoinemia significantly decreased after substitution (17.14mg/L
      with di-hydan versus 12.17mg/L with diphantoine, P<8 10(-6)). Moreover an
      increase in post substitution posology of diphantoine was noticed (264.77mg/L
      with di-hydan versus 274.73mg/L with diphantoine), although not significant
      (P=0.11). Increase of seizures was non-significant (P = 0.09). The decrease of
      phenytoinemia was probably due to the difference of composition between the
      drugs: a 100mg di-hydan tablet contains 100mg of phenytoin whereas a 100mg
      diphantoine tablet contains 92mg. The specific non-linear kinetics of phenytoin
      reinforces this difference. A prospective study could better evaluate the risk of
      substituting di-hydan with diphantoine. 

PMID- 25575611
TI  - Impact of repeated measures of joint space width on the sample size calculation:
      An application to hip osteoarthritis.
AB  - OBJECTIVE: The aims of the study were to investigate the impact of aggregation of
      repeated readings (a) on minimising variability of joint space width (JSW)
      measurements based on calculation of the smallest detectable difference (SDD) and
      (b) on sample size calculation in a hip OA randomized controlled trial (RCT).
      METHODS: (a) Post-hoc analysis of 50 radiographs from a hip OA RCT (ECHODIAH).
      JSW reliability was calculated by the SDD through the aggregation of repeated
      readings of hip OA radiographs by an experienced rheumatologist. (b) The observed
      SDDs were applied to the real ECHODIAH data, to determine the post-hoc
      theoretical sample sizes. RESULTS: (a) Although the intra-reader reliability did
      not improve, SDDs decreased from 0.75 mm to 0.27 mm when aggregating two or more
      consecutive readings. (b) A significant decrease of sample size was noticed until
      three consecutive paired JSW measurements, with a sample size ranging from 6588
      patients per group (SDD=0.75 mm) to 377 patients (SDD=0.45 mm). However, an
      increase of the sample size was observed for smaller SDDs. CONCLUSION: In hip OA,
      the aggregation of repeated radiograph readings leads to a significant decrease
      in SDD, although the intra-reader reliability of the experienced reader remains
      stable. The decrease in SDD allowed to reduce significantly the post-hoc
      calculation of sample size until a SDD value of 0.45 mm. For smaller cut-offs of
      radiological progression, the sample size increased again indicating that gain in
      sensitivity does not automatically lead to gain in sample size, particularly if
      the treatment effect is limited.

PMID- 25575612
TI  - Bilateral radiolucent hand lesions in a patient with lymphoma mimicking
      sarcoidosis.

PMID- 25575614
TI  - Characterization of Sphingomonas sp. JB13 exo-inulinase: a novel detergent-, salt
      , and protease-tolerant exo-inulinase.
AB  - A glycoside hydrolase family 32 exo-inulinase gene was cloned from Sphingomonas
      sp. JB13 and expressed in Escherichia coli BL21 (DE3). The purified recombinant
      enzyme (rInuAJB13) showed an apparently optimal activity at pH 5.5 and 55 
      degrees C and remained activity at 10-70  degrees C. The addition of most metal
      ions and chemical reagents showed little or no effect (retaining more than 76.5 %
      activity) on the enzyme activity, notably the addition of surfactants SDS, CTAB,
      Tween 80, and Triton X-100. Most local liquid detergents, including Balin, Walch,
      Ariel, Tide, Tupperware, and Bluemoon, also showed little or no effect (retaining
      more than 77.8 % activity) on the enzyme activity. rInuAJB13 exhibited 135.3
      163.6 % activity at the NaCl concentration of 1.0-4.5 M. After incubation with up
      to 57.0 mg mL(-1) trypsin and 90.0 mg mL(-1) proteinase K at 37  degrees C for 60
      min (pH 7.2), rInuAJB13 retained more than 80 % of its initial activity. The
      enzyme presents a high proportion (28.0 %) of amino acid residues G, A, and V.
      This paper is the first to report a detergent-, salt-, and protease-tolerant exo
      inulinase.

PMID- 25575613
TI  - Novel characteristics of a carbohydrate-binding module 20 from hyperthermophilic
      bacterium.
AB  - In this study, a gene fragment coding carbohydrate-binding module 20 (CBM20) in
      the amylopullulanase (APU) gene was cloned from the hyperthermophilic bacteria
      Thermoanaerobacter pseudoethanolicus 39E and expressed in Escherichia coli. The
      protein, hereafter Tp39E, possesses very low sequence similarity with the CBM20s
      previously reported and has no starch binding site 2. Tp39E did not demonstrate
      thermal denaturation at 50  degrees C; however, thermal unfolding of the protein
      was observed at 59.5  degrees C. A binding assay with Tp39E was conducted using
      various soluble and insoluble substrates, and starch was the best binding
      polysaccharide. Intriguingly, Tp39E bound, to a lesser extent, to soluble and
      insoluble xylan as well. The dissociation constant (K d) and the maximum specific
      binding (B max) of Tp39E to corn starch granules were 0.537 MUM and 5.79 MUM/g,
      respectively, at pH 5.5 and 20  degrees C. 99APU1357 with a Tp39E domain
      exhibited 2.2-fold greater activity than a CBM20-truncation mutant when starch
      granules were the substrate. Tp39E was an independently thermostable CBM and had
      a considerable effect on APU activity in the hydrolysis of insoluble substrates.

PMID- 25575616
TI  - Reliability and Validity of the Before-School Functioning Scale in Children With
      ADHD.
AB  - OBJECTIVE: Children with ADHD frequently manifest behavioral difficulties in the
      morning prior to school. We sought to assess the reliability and validity of the
      Before-School Functioning Questionnaire (BSFQ) as a measure of morning behaviors
      impaired by ADHD. METHOD: We used pre-treatment data from a randomized crossover
      study of 6- to 12-year-old participants comparing the methylphenidate transdermal
      delivery system (MTS) with a placebo transdermal system (PTS) for a total of 4
      weeks. RESULTS: The BSFQ investigator-rated scale shows very good internal
      homogeneity (Cronbach's alpha = .91), good test-retest reliability ( r = .60),
      good concurrent validity ( r range = .42-.86), and a strong treatment effect
      (effect size = -.93). The self-rated BSFQ showed lower levels of reliability and
      validity. CONCLUSION: The investigator-rated BSFQ should be used in future trials
      of ADHD medications aimed at assessing efficacy in the morning before school.

PMID- 25575615
TI  - Differential expression of sulfur assimilation pathway genes in Acidithiobacillus
      ferrooxidans under Cd2+ stress: evidence from transcriptional, enzymatic, and
      metabolic profiles.
AB  - Acidithiobacillus ferrooxidans is a heavy metal-tolerant acidophilic
      chemolithotroph found in acidic mine effluent and is used commercially in the
      bioleaching of sulfide ores. In this work, we investigated the interplay between
      divalent cadmium (Cd(2+)) resistance and expression of genes involved in the
      sulfur assimilation pathway (SAP). We also investigated the response of the thiol
      containing metal-chelating metabolites, cysteine and glutathione(GSH), to
      increasing Cd(2+) concentrations. During growth in the presence of 30 mM Cd(2+),
      the concentrations of mRNA for 5 genes in the SAP pathway increased more than
      fourfold: these encode ATP sulfurylase (ATPS), adenosine 5'-phosphosulfate (APS)
      reductase, sulfite reductase (SiR), serine acetyltransferase (SAT) and O
      acetylserine (thiol) lyase (OAS-TL). Increased transcription was also reflected
      in increased enzyme activities: those of SAT and adenosylphosphosulfate reductase
      (APR) reached a peak of 26- and 15.8-fold, respectively, compared to the control
      culture in the presence of 15 mM Cd(2+). In contrast, the activity of OAS-TL,
      which is responsible for the biosynthesis of cysteine, was diminished. At the
      metabolite level, the intracellular cysteine and GSH contents nearly doubled.
      These results suggested that Cd(2+) induced transcription of SAP genes, while
      directly inhibiting the activities of some enzymes (e.g., OAS-TL). Overall, these
      results are consistent with a detoxification/resistance mechanism involving
      enhanced sulfur uptake and sequestration of Cd(2+) by cysteine and glutathione.

PMID- 25575617
TI  - Intensity modulated radiotherapy for locally advanced and metastatic pancreatic
      cancer: a mono-institutional retrospective analysis.
AB  - BACKGROUND: To evaluate the role of intensity modulated radiotherapy (IMRT) for
      locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC),
      and the prognostic factors in the setting of multidisciplinary approach
      strategies. METHODS: 63 patients with LAPC and MPC receiving IMRT in our
      institution were retrospectively identified. Information on patient baseline,
      treatment characteristics and overall survival (OS) time were collected. Data of
      pain relief and toxicity were evaluated. Univariate and multivariate analyses
      were conducted to investigate the prognostic factors. RESULTS: All patients
      received IMRT with a median dose of 46.0 Gy. The median OS for LAPC and MPC
      patients were 15.7 months and 8.0 months, respectively (p = 0.029). Symptomatic
      improvements were observed in the 44 patients with abdominal/back pain after
      radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in those
      with severe pain. Only 13.9% and 14.8% cases presented Grade >= 3 hematologic
      toxicities in RT and CCRT group, while no cases developed Grade >= 3 non
      hematologic toxicities in both groups. Multivariate analysis indicated that
      tumors located in pancreas body/tail (HR 0.28, p = 0.008), pretreatment CA19-9 <
      1000 U/mL (HR 0.36, p = 0.029) and concurrent chemotherapy (HR 0.37, p = 0.016)
      were independent favorable predictors for OS. CONCLUSIONS: CCRT further improved
      OS for LAPC and MPC with acceptable toxicities, and use of RT markedly alleviated
      pain. Tumors located in pancreas body/tail, pretreatment CA19-9 level of < 1000
      U/mL and CCRT were associated with better OS. However, regional intra-arterial
      chemotherapy did not show any survival benefit in our study.

PMID- 25575618
TI  - Spatiotemporal spread of the 2014 outbreak of Ebola virus disease in Liberia and
      the effectiveness of non-pharmaceutical interventions: a computational modelling
      analysis.
AB  - BACKGROUND: The 2014 epidemic of Ebola virus disease in parts of west Africa
      defines an unprecedented health threat. We developed a model of Ebola virus
      transmission that integrates detailed geographical and demographic data from
      Liberia to overcome the limitations of non-spatial approaches in projecting the
      disease dynamics and assessing non-pharmaceutical control interventions. METHODS:
      We modelled the movements of individuals, including patients not infected with
      Ebola virus, seeking assistance in health-care facilities, the movements of
      individuals taking care of patients infected with Ebola virus not admitted to
      hospital, and the attendance of funerals. Individuals were grouped into randomly
      assigned households (size based on Demographic Health Survey data) that were
      geographically placed to match population density estimates on a grid of 3157
      cells covering the country. The spatial agent-based model was calibrated with a
      Markov chain Monte Carlo approach. The model was used to estimate Ebola virus
      transmission parameters and investigate the effectiveness of interventions such
      as availability of Ebola treatment units, safe burials procedures, and household
      protection kits. FINDINGS: Up to Aug 16, 2014, we estimated that 38.3% of
      infections (95% CI 17.4-76.4) were acquired in hospitals, 30.7% (14.1-46.4) in
      households, and 8.6% (3.2-11.8) while participating in funerals. We noted that
      the movement and mixing, in hospitals at the early stage of the epidemic, of
      patients infected with Ebola virus and those not infected was a sufficient driver
      of the reported pattern of spatial spread. The subsequent decrease of incidence
      at country and county level is attributable to the increasing availability of
      Ebola treatment units (which in turn contributed to drastically decreased
      hospital transmission), safe burials, and distribution of household protection
      kits. INTERPRETATION: The model allows assessment of intervention options and the
      understanding of their role in the decrease in incidence reported since Sept 7,
      2014. High-quality data (eg, to estimate household secondary attack rate, contact
      patterns within hospitals, and effects of ongoing interventions) are needed to
      reduce uncertainty in model estimates. FUNDING: US Defense Threat Reduction
      Agency, US National Institutes of Health.

PMID- 25575619
TI  - Controlling Ebola: key role of Ebola treatment centres.

PMID- 25575620
TI  - Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects.
AB  - BACKGROUND: After no research in humans for >40 years, there is renewed interest
      in using lysergic acid diethylamide (LSD) in clinical psychiatric research and
      practice. There are no modern studies on the subjective and autonomic effects of
      LSD, and its endocrine effects are unknown. In animals, LSD disrupts prepulse
      inhibition (PPI) of the acoustic startle response, and patients with
      schizophrenia exhibit similar impairments in PPI. However, no data are available
      on the effects of LSD on PPI in humans. METHODS: In a double-blind, randomized,
      placebo-controlled, crossover study, LSD (200 MUg) and placebo were administered
      to 16 healthy subjects (8 women, 8 men). Outcome measures included psychometric
      scales; investigator ratings; PPI of the acoustic startle response; and
      autonomic, endocrine, and adverse effects. RESULTS: Administration of LSD to
      healthy subjects produced pronounced alterations in waking consciousness that
      lasted 12 hours. The predominant effects induced by LSD included visual
      hallucinations, audiovisual synesthesia, and positively experienced derealization
      and depersonalization phenomena. Subjective well-being, happiness, closeness to
      others, openness, and trust were increased by LSD. Compared with placebo, LSD
      decreased PPI. LSD significantly increased blood pressure, heart rate, body
      temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine.
      Adverse effects produced by LSD completely subsided within 72 hours. No severe
      acute adverse effects were observed. CONCLUSIONS: In addition to marked
      hallucinogenic effects, LSD exerts methylenedioxymethamphetamine-like
      empathogenic mood effects that may be useful in psychotherapy. LSD altered
      sensorimotor gating in a human model of psychosis, supporting the use of LSD in
      translational psychiatric research. In a controlled clinical setting, LSD can be
      used safely, but it produces significant sympathomimetic stimulation.

PMID- 25575621
TI  - Host effects contributing to cancer therapy resistance.
AB  - There are several approaches for the management of malignant disease. However,
      tumor resistance to therapy is still a major challenge in the clinic. Efflux
      transporters, genetic responses and enzyme activity in tumor cells are examples
      of the main modalities that account for resistance to therapy. In addition,
      emerging evidence suggests that the host also plays a significant role in
      promoting therapy resistance. Recruitment of different host cell types to the
      treated tumor site occurs in response to a range of therapies, including
      chemotherapy, radiation and even targeted drugs. This host response may have a
      protective effect on the tumor cells, not only negating anti-tumor activity, but
      also promoting a resistant tumor. In this review, we focus on host-tumor
      interactions leading to therapy resistance with special emphasis on different
      host cells and secreted factors within the tumor microenvironment. The
      development of novel inhibitors that block the host response to therapy could be
      used as a treatment strategy to enhance therapy outcomes and survival. 

PMID- 25575622
TI  - Adolescent judgments and reasoning about the failure to include peers with social
      disabilities.
AB  - Adolescents with autism spectrum disorder often do not have access to crucial
      peer social activities. This study examines how typically developing adolescents
      evaluate decisions not to include a peer based on disability status, and the
      justifications they apply to these decisions. A clinical interview methodology
      was used to elicit judgments and justifications across four contexts. We found
      adolescents are more likely to judge the failure to include as acceptable in
      personal as compared to public contexts. Using logistic regression, we found that
      adolescents are more likely to provide moral justifications as to why failure to
      include is acceptable in a classroom as compared to home, lab group, and soccer
      practice contexts. Implications for intervention are also discussed. 

PMID- 25575625
TI  - The human histaminergic system in neuropsychiatric disorders.
AB  - Histaminergic neurons are exclusively located in the hypothalamic tuberomamillary
      nucleus, from where they project to many brain areas. The histaminergic system is
      involved in basic physiological functions, such as the sleep-wake cycle, energy
      and endocrine homeostasis, sensory and motor functions, cognition, and attention,
      which are all severely affected in neuropsychiatric disorders. Here, we present
      recent postmortem findings on the alterations in this system in neuropsychiatric
      disorders, including Parkinson's disease (PD), Alzheimer's disease (AD),
      Huntington's disease (HD), depression, and narcolepsy. In addition, we highlight
      the need to validate animal models for these diseases and also for Tourette's
      syndrome (TS) in relation to alterations in the histaminergic system. Moreover,
      we discuss the potential for, and concerns over, the use of novel histamine 3
      receptor (H3R) antagonists/inverse agonists as treatment for such disorders. 

PMID- 25575626
TI  - Chemical constituents from the aerial parts of Melandrium firmum.
AB  - Two new anthraquinones, melrubiellin C (1) and melrubiellin D (2), were isolated
      from the aerial parts of Melandrium firmum Rohrbach, together with eight known
      compounds (3-10). The structures of these compounds were elucidated using 1D and
      2D NMR (COSY, HMQC, HMBC and NOESY) experiments. All isolated compounds were
      tested for their cytotoxicity against NCI-H460, Hep G2, MKN-28 and A-549 cells.
      Of these 10 compounds, 1 and 2 exhibited moderate cytotoxicity with IC50 values
      ranging from 9.54 to 32.41 MUM.

PMID- 25575627
TI  - The double-edged sword of AMPK signaling in cancer and its therapeutic
      implications.
AB  - 5'-AMP-activated protein kinase (AMPK) plays a pivotal role in maintaining energy
      and redox homeostasis under various metabolic stress conditions. Metabolic
      adaptation, which can be triggered by the activation of AMPK during metabolic
      stress, is the critical process for cell survival through the maintenance of ATP
      and NADPH levels. The importance of such regulation of fundamental process poses
      the AMPK signaling pathway in one of the most attractive therapeutic targets in
      many pathologies such as diabetes and cancer. In cancer, however, accumulating
      data suggest that the role of AMPK would not be simply defined as anti- or pro
      tumorigenic, but it seems to have two faces like a double-edged sword.
      Importantly, recent studies showed that the anti-tumorigenic effects of many
      'indirect' AMPK activators such as anti-diabetic biguanides are not dependent on
      AMPK; rather the activation of AMPK induces the resistance to their cytotoxic
      effects, emphasizing the pro-tumorigenic effect of AMPK. In this review, we
      summarize and discuss recent findings suggesting the two faces of AMPK in cancer,
      and discuss how we can exploit this unique feature of AMPK for novel therapeutic
      intervention. 

PMID- 25575628
TI  - Cancer metabolism: targeting cancer universality.
AB  - Cancer metabolism has taken a step forward lately using modern molecular and
      chemical biology techniques. The future direction will most likely be defined by
      scientists looking for the commonality between cancer types, using metabolic gene
      signatures, RNA and protein signatures of metabolic enzymes. Cancer metabolism
      may be the missing link between the inductive and deductive methods in the
      scientific method. 

PMID- 25575629
TI  - [Disease and disability. The ICF model].
AB  - Diagnoses alone, e.g. according to the international classification of diseases
      10 (ICD-10), do not give information on the illness severity, treatment needs and
      consequences. This depends on the functional health status, e.g. according to the
      international classification of functioning, disability and health (ICF) which
      discriminates between impairment of functions, limitations in activity and
      capacity and participation restrictions. The German social law (SGB IX) defines
      disability as a chronic health status which lasts longer than 6 months and which
      results in participation restrictions. Participation restrictions are impaired
      capacities which not allow context or role requirements to be fulfilled. There
      are many instruments to measure capacities, such as the Mini-ICF-APP which was
      especially developed for mental disorders. As most mental disorders are chronic
      illnesses which lead to participation restrictions they must be conceptualized as
      mental disabilities. The consequence is that they must be treated under a social
      psychiatric perspective focussing on functions, capacities and context alike. 

PMID- 25575630
TI  - [The contribution of neuroscience to the concept of mental disorder].
AB  - AIM: In this article the contribution of neuroscience to the concept of mental
      disorder is discussed against the background of biological psychiatry and
      philosophy of mind. RESULTS AND DISCUSSION: Psychiatric nosology is confronted by
      similar challenges as every general nosology. Among these are the role of
      dysfunction versus "normal" function, the fuzzy boundary of health and disorder,
      the role of subjective suffering and the role of causal mechanisms. In the case
      of mental disorders, a further issue is that every nosology has to take a stance
      about what mental processes actually are. In this article, the disorder concepts
      of the fifth edition of the diagnostic and statistical manual of mental disorders
      (DSM-5) and of the research domain criteria (RDoC) approach of the National
      Institute of Mental Health are explained and discussed. Furthermore, it is argued
      that a sound psychiatric nosology should not be purely descriptive but should
      also take the causal mechanisms of disorders into account. A recent suggestion,
      the theory of mechanistic property clusters, is introduced. Taking recent
      discussion on the philosophy of mind into account, it becomes apparent that the
      obvious assumption that mental disorders are (nothing more than) disorders of the
      brain might not be correct: at least this has been suggested by the theory of
      situated cognition. It is concluded that a sound psychiatric nosology will have
      to consider contemporary theories of mental disorders; however, such a synthesis
      has yet to be formulated.

PMID- 25575631
TI  - [Intraneural hemangioma of the ulnar nerve].

PMID- 25575632
TI  - [Hippocampal stroke].
AB  - Unilateral cerebral ischemia of the hippocampus is very rare. This paper reviews
      the literature and presents the case of a 59-year-old woman with an amnestic
      syndrome due to a left hippocampal stroke. The patient suffered from retrograde
      amnesia which was most severe over the 2 days prior to presenting and a slight
      anterograde amnesia. In addition, a verbal memory disorder was confirmed 1 week
      after admission by neurological tests. As risk factors, arterial hypertension and
      a relative hyper-beta lipoproteinemia were found. This case shows that unilateral
      amnestic stroke, e.g. in the hippocampus region, may be the cause of an amnestic
      syndrome and should be included in the differential diagnostics. 

PMID- 25575633
TI  - The hearts of competitive athletes: an up-to-date overview of exercise-induced
      cardiac adaptations.
AB  - Intense and regular physical exercise is responsible for various cardiac changes
      (electrical, structural and functional) that represent physiological adaptation
      to exercise training. This remodeling, commonly referred to as 'athlete's heart',
      can overlap with several pathological entities, in which sudden cardiac death may
      be the first clinical presentation. Although pre-competitive screening can
      identify athletes with life-threatening cardiovascular abnormalities, there are
      no widely used standardized pre-participation programs and those currently
      implemented are controversial. Data from personal and family history, features of
      physical examination and changes in the 12-lead electrocardiogram can raise the
      suspicion of cardiac disease and lead to early detection of entities such as
      hypertrophic cardiomyopathy. However, interpreting the electrocardiogram is often
      challenging, because some changes are considered physiological in athletes. Thus,
      clinical decision-making in such cases can prove difficult: missing a condition
      associated with an increased risk of life-threatening events, or conversely,
      mislabeling an athlete with a disease that leads to unnecessary disqualification,
      are both situations to avoid. This paper provides an up-to-date review of the
      physiological cardiac effects of exercise training and highlights key points that
      should be taken into consideration in the assessment of young competitive
      athletes. 

PMID- 25575634
TI  - Successful percutaneous repositioning of a dislodged atrial pacemaker lead with a
      deflectable catheter.

PMID- 25575635
TI  - Mitochondrial energy failure in HSD10 disease is due to defective mtDNA
      transcript processing.
AB  - Muscle, heart and liver were analyzed in a male subject who succumbed to HSD10
      disease. Respiratory chain enzyme analysis and BN-PAGE showed reduced activities
      and assembly of complexes I, III, IV, and V. The mRNAs of all RNase P subunits
      were preserved in heart and overexpressed in muscle, but MRPP2 protein was
      severely decreased. RNase P upregulation correlated with increased expression of
      mitochondrial biogenesis factors and preserved mitochondrial enzymes in muscle,
      but not in heart where this compensatory mechanism was incomplete. We demonstrate
      elevated amounts of unprocessed pre-tRNAs and mRNA transcripts encoding
      mitochondrial subunits indicating deficient RNase P activity. This study provides
      evidence of abnormal mitochondrial RNA processing causing mitochondrial energy
      failure in HSD10 disease. 

PMID- 25575636
TI  - Polymerase gamma mutator mice rely on increased glycolytic flux for energy
      production.
AB  - Several studies have illustrated that the polymerase gamma mutator (PolG) mice
      have reduced mitochondrial content secondary to systemic mitochondrial
      dysfunction, and subsequently a lower capacity to perform aerobic respiration and
      endurance exercise. We sought to delineate the extent of glycolysis as a means of
      energy production in the PolG mice in the absence of optimal mitochondrial
      function. PolG mice display an enhanced reliance on glycolysis as compared to
      their wild-type counterparts. This is evident by the resting hypoglycemia, higher
      PFK content, and elevated plasma lactate levels in the PolG mice. In vitro
      experiments provide further proof that PolG derived dermal fibroblasts have a
      higher rate of, and capacity for, glycolysis. PolG mice also have enhanced
      capacity to perform hepatic gluconeogenesis that is likely enhancing the Cori
      cycle capacity. 

PMID- 25575637
TI  - In reply: Is propofol more neurotoxic in the developing brain?

PMID- 25575638
TI  - Towards a better preclinical model of PTSD: characterizing animals with weak
      extinction, maladaptive stress responses and low plasma corticosterone.
AB  - Most of the available preclinical models of PTSD have focused on isolated
      behavioural aspects and have not considered individual variations in response to
      stress. We employed behavioural criteria to identify and characterize a
      subpopulation of rats that present several features analogous to PTSD-like states
      after exposure to classical fear conditioning. Outbred Sprague-Dawley rats were
      segregated into weak- and strong-extinction groups on the basis of behavioural
      scores during extinction of conditioned fear responses. Animals were subsequently
      tested for anxiety-like behaviour in the open-field test (OFT), novelty
      suppressed feeding (NSF) and elevated plus maze (EPM). Baseline plasma
      corticosterone was measured prior to any behavioural manipulation. In a second
      experiment, rats underwent OFT, NSF and EPM prior to being subjected to fear
      conditioning to ascertain whether or not pre-stress levels of anxiety-like
      behaviours could predict extinction scores. We found that 25% of rats exhibit low
      extinction rates of conditioned fear, a feature that was associated with
      increased anxiety-like behaviour across multiple tests in comparison to rats
      showing strong extinction. In addition, weak-extinction animals showed low levels
      of corticosterone prior to fear conditioning, a variable that seemed to predict
      extinction recall scores. In a separate experiment, anxiety measures taken prior
      to fear conditioning were not predictive of a weak-extinction phenotype,
      suggesting that weak-extinction animals do not show detectable traits of anxiety
      in the absence of a stressful experience. These findings suggest that extinction
      impairment may be used to identify stress-vulnerable rats, thus providing a
      useful model for elucidating mechanisms and investigating potential treatments
      for PTSD.

PMID- 25575639
TI  - Ubiquitin-specific protease 14 regulates c-Jun N-terminal kinase signaling at the
      neuromuscular junction.
AB  - BACKGROUND: Ubiquitin-specific protease 14 (USP14) is one of three proteasome
      associated deubiquitinating enzymes that remove ubiquitin from proteasomal
      substrates prior to their degradation. In vitro evidence suggests that inhibiting
      USP14's catalytic activity alters the turnover of ubiquitinated proteins by the
      proteasome, although whether protein degradation is accelerated or delayed seems
      to be cell-type and substrate specific. For example, combined inhibition of USP14
      and the proteasomal deubiquitinating enzyme UCH37 halts protein degradation and
      promotes apoptosis in multiple myeloma cells, whereas USP14 inhibition alone
      accelerates the degradation of aggregate-prone proteins in immortalized cell
      lines. These findings have prompted interest in USP14 as a therapeutic target
      both inside and outside of the nervous system. However, loss of USP14 in the
      spontaneously occurring ataxia mouse mutant leads to a dramatic neuromuscular
      phenotype and early perinatal lethality, suggesting that USP14 inhibition may
      have adverse consequences in the nervous system. We therefore expressed a
      catalytically inactive USP14 mutant in the mouse nervous system to determine
      whether USP14's catalytic activity is required for neuromuscular junction (NMJ)
      structure and function. RESULTS: Mice expressing catalytically inactive USP14 in
      the nervous system exhibited motor deficits, altered NMJ structure, and synaptic
      transmission deficits that were similar to what is observed in the USP14
      deficient ataxia mice. Acute pharmacological inhibition of USP14 in wild type
      mice also reduced NMJ synaptic transmission. However, there was no evidence of
      altered proteasome activity when USP14 was inhibited either genetically or
      pharmacologically. Instead, these manipulations increased the levels of non
      proteasome targeting ubiquitin conjugates. Specifically, we observed enhanced
      proteasome-independent ubiquitination of mixed lineage kinase 3 (MLK3).
      Consistent with the direct activation of MLK3 by ubiquitination, we also observed
      increased activation of its downstrea targets MAP kinase kinase 4 (MKK4) and c
      Jun N-terminal kinase (JNK). In vivo inhibition of JNK improved motor function
      and synapse structure in the USP14 catalytic mutant mice. CONCLUSIONS: USP14's
      catalytic activity is required for nervous system structure and function and has
      an ongoing role in NMJ synaptic transmission. By regulating the ubiquitination
      status of protein kinases, USP14 can coordinate the activity of intracellular
      signaling pathways that control the development and activity of the NMJ.

PMID- 25575640
TI  - Immunonutrition stimulates immune functions and antioxidant defense capacities of
      leukocytes in radiochemotherapy-treated head & neck and esophageal cancer
      patients: A double-blind randomized clinical trial.
AB  - BACKGROUND: Immunonutrition has been reported to improve the immune status of
      perioperative cancer patients, thereby reducing complications and length of
      hospital stay. AIM: This study aimed to assess whether immunonutrition enriched
      in arginine, EPA & DHA and nucleotides could impact the immune cells responses in
      head & neck and esophageal cancer patients treated by radiochemotherapy (RCT).
      METHODS: A double-blind clinical trial was carried out in 28 patients randomized
      into two groups, receiving either an immunomodulating enteral nutrition formula
      (IEN, n = 13, Impact((r)), Nestle) or an isoenergetic isonitrogenous standard
      enteral nutrition formula (SEN, n = 15) throughout RCT (5-7 weeks). After
      isolation from whole blood, immune cells metabolism and functions were assessed
      at the beginning (Db) and at the end (De) of RCT. RESULTS: Immunonutrition
      maintained CD4(+)/CD8(+) T-lymphocyte counts ratio and CD3 membrane expression
      between Db and De. Polymorphonuclear cells CD62L and CD15 densities and ROS
      production were increased in IEN patients. Peripheral blood mononuclear cells
      (PBMC) production of pro-inflammatory prostaglandin-E2 was stable in IEN patients
      and lower than in SEN patients at De. Genes coding for immune receptors,
      antioxidant enzymes and NADPH oxidase subunits were overexpressed in the PBMC of
      IEN vs SEN patients at De. CONCLUSION: Immunonutrition can enhance immune cell
      responses through the modulation of their phenotypes and functions. By modulating
      the gene expression of immune cells, immunonutrition could make it easier for the
      organism to adapt to the systemic inflammation and oxidative stress induced by
      RCT. CLINICAL TRIAL REGISTRATION: This clinical trial has been registered on
      ClinicalTrial.gov website: NCT00333099.

PMID- 25575641
TI  - To what extent do structural quality indicators of (nutritional) care influence
      malnutrition prevalence in nursing homes?
AB  - BACKGROUND & AIMS: Many residents in European healthcare institutions are
      malnourished, with reported malnutrition prevalence rates of up to 60%. Due to
      the negative effects of malnutrition it is important to optimize the quality of
      nutritional care. If structural quality indicators of nutritional care might
      improve resident care and outcome is not yet known. The aim of this study is to
      explore whether structural quality indicators for nutritional care influence
      malnutrition prevalence in Dutch, German and Austrian nursing homes. METHODS:
      This study follows a cross-sectional, multi-center design. Data were collected by
      using a standardised questionnaire at resident, ward and institution level.
      RESULTS: Data from 214 nursing homes (NL = 133, G = 61, A = 20) were analysed.
      The prevalence of malnutrition varied significantly between the three countries
      (NL = 18.2% G = 20.1% A = 22.5%). Two structural quality indicators at ward level
      namely (1) the policy that the care file should include the nutritional intake
      for each patient and (2) having a weight measurement policy at ward level are
      predictive for malnutrition prevalence. Furthermore also the variable country was
      of influence. CONCLUSIONS: A policy of registering nutritional intake in the file
      of the patient and a policy to assess the patient's weight regularly have a
      positive influence on malnutrition prevalence.

PMID- 25575642
TI  - The marmoset as a model for the study of primate parental behavior.
AB  - Parental behavior is important for the development of mammalian offspring.
      Research on the mechanisms underlying parental behavior, however, has been
      largely restricted to rodent models. As a consequence, although research on
      parent-infant relationships has been conducted using macaque monkeys for more
      than half a century, little is known about the neural mechanisms and brain
      regions associated with such behaviors in primates. This article reviews parental
      behavior and its endocrinological mechanisms in marmosets and tamarins, both
      cooperative breeders in the callitrichid family, and compares these findings with
      studies of macaque monkeys. The paper examines the similarities and differences
      between marmosets and humans, and suggests the possibility that marmosets can be
      a model for future studies of the neural underpinnings and endocrinology
      underlying human parental behavior. 

PMID- 25575643
TI  - The spinal cord of the common marmoset (Callithrix jacchus).
AB  - The marmoset spinal cord possesses all the characteristic features of a typical
      mammalian spinal cord, but with some interesting variation in the levels of
      origin of the limb nerves. In our study Nissl and ChAT sections of the each
      segment of the spinal cord in two marmosets (Ma5 and Ma8), we found that the
      spinal cord can be functionally and anatomically divided into six regions: the
      prebrachial region (C1 to C3); the brachial region (C4 to C8) - segments
      supplying the upper limb; the post-brachial region (T1 to L1) - containing the
      sympathetic outflow, and supplying the hypaxial muscles of the body wall; the
      crural region (L2 to L5) - segments supplying the lower limb; the postcrural
      region (L6) - containing the parasympathetic outflow; and the caudal region (L7
      to Co4) - supplying the tail. In the rat, mouse, and rhesus monkey, the
      prebrachial region consists of segments C1 to C4 (with the phrenic nucleus
      located at the C4 segment), and the brachial region extends from C5 to T1
      inclusive. The prefixing of the upper limb outflow in these two marmosets mirrors
      the finding in the literature that a large C4 contribution to the brachial plexus
      is common in humans. 

PMID- 25575644
TI  - Hydrogen sulfide attenuates high fat diet-induced cardiac dysfunction via the
      suppression of endoplasmic reticulum stress.
AB  - Diabetic cardiomyopathy is a significant contributor to the morbidity and
      mortality associated with diabetes and metabolic syndrome. However, the
      underlying molecular mechanisms that lead to its development have not been fully
      elucidated. Hydrogen sulfide (H2S) is an endogenously produced signaling molecule
      that is critical for the regulation of cardiovascular homeostasis. Recently,
      therapeutic strategies aimed at increasing its levels have proven
      cardioprotective in models of acute myocardial ischemia-reperfusion injury and
      heart failure. The precise role of H2S in the pathogenesis of diabetic
      cardiomyopathy has not yet been established. Therefore, the goal of the present
      study was to evaluate circulating and cardiac H2S levels in a murine model of
      high fat diet (HFD)-induced cardiomyopathy. Diabetic cardiomyopathy was produced
      by feeding mice HFD (60% fat) chow for 24 weeks. HFD feeding reduced both
      circulating and cardiac H2S and induced hallmark features of type-2 diabetes. We
      also observed marked cardiac dysfunction, evidence of cardiac enlargement,
      cardiac hypertrophy, and fibrosis. H2S therapy (SG-1002, an orally active H2S
      donor) restored sulfide levels, improved some of the metabolic perturbations
      stemming from HFD feeding, and attenuated HFD-induced cardiac dysfunction.
      Additional analysis revealed that H2S therapy restored adiponectin levels and
      suppressed cardiac ER stress stemming from HFD feeding. These results suggest
      that diminished circulating and cardiac H2S levels play a role in the
      pathophysiology of HFD-induced cardiomyopathy. Additionally, these results
      suggest that H2S therapy may be of clinical importance in the treatment of
      cardiovascular complications stemming from diabetes. 

PMID- 25575645
TI  - Risk of merkel cell carcinoma after solid organ transplantation.
AB  - BACKGROUND: Solid organ transplant recipients have elevated risks of virus
      related cancers, in part because of long-term immunosuppression. Merkel cell
      carcinoma (MCC) is an aggressive skin cancer recently found to have a viral
      origin, but little is known regarding the occurrence of MCC after transplant.
      METHODS: We linked the US Scientific Registry of Transplant Recipients with data
      from 15 population-based cancer registries to ascertain MCC occurrence among
      189498 solid organ transplant recipients from 1987 to 2009. Risks for MCC
      following transplantation were compared with the general population using
      standardized incidence ratios, and Poisson regression was used to compare
      incidence rates according to key patient and transplant characteristics. All
      statistical tests were two-sided. RESULTS: After solid organ transplantation,
      overall risk of MCC was increased 23.8-fold (95% confidence interval = 19.6 to
      28.7, n = 110). Adjusted risks were highest among older recipients, increased
      with time since transplantation, and varied by organ type (all P <= .007).
      Azathioprine, cyclosporine, and mTOR inhibitors given for maintenance
      immunosuppression increased risk, and non-Hispanic white recipients on
      cyclosporine and azathioprine experienced increasing MCC risk with lower latitude
      of residence (ie, higher ultraviolet radiation exposure, P = .012). CONCLUSIONS:
      MCC risk is sharply elevated after solid organ transplant, likely resulting from
      long-term immunosuppression. Immunosuppressive medications may act
      synergistically with ultraviolet radiation to increase risk.

PMID- 25575646
TI  - Merkel cell carcinoma and immunosuppression: what we still need to know.

PMID- 25575648
TI  - Erratum to: The Ability to Diagnose Intrahepatic Cholangiocarcinoma Definitively
      Using Novel Branched DNA-Enhanced Albumin RNA In Situ Hybridization Technology.

PMID- 25575647
TI  - Synaptic therapy in Alzheimer's disease: a CREB-centric approach.
AB  - Therapeutic attempts to cure Alzheimer's disease (AD) have failed, and new
      strategies are desperately needed. Motivated by this reality, many laboratories
      (including our own) have focused on synaptic dysfunction in AD because synaptic
      changes are highly correlated with the severity of clinical dementia. In
      particular, memory formation is accompanied by altered synaptic strength, and
      this phenomenon (and its dysfunction in AD) has been a recent focus for many
      laboratories. The molecule cyclic adenosine monophosphate response element
      binding protein (CREB) is at a central converging point of pathways and
      mechanisms activated during the processes of synaptic strengthening and memory
      formation, as CREB phosphorylation leads to transcription of memory-associated
      genes. Disruption of these mechanisms in AD results in a reduction of CREB
      activation with accompanying memory impairment. Thus, it is likely that
      strategies aimed at these mechanisms will lead to future therapies for AD. In
      this review, we will summarize literature that investigates 5 possible
      therapeutic pathways for rescuing synaptic dysfunction in AD: 4 enzymatic
      pathways that lead to CREB phosphorylation (the cyclic adenosine monophosphate
      cascade, the serine/threonine kinases extracellular regulated kinases 1 and 2,
      the nitric oxide cascade, and the calpains), as well as histone
      acetyltransferases and histone deacetylases (2 enzymes that regulate the histone
      acetylation necessary for gene transcription). 

PMID- 25575649
TI  - Real clinical practice of catheter therapy for deep venous thrombosis:
      periprocedural and 6-month outcomes from the EDO registry.
AB  - A recent national study in Japan indicated that 5.8 % of deep venous thrombosis
      (DVT) patients were treated using endovascular procedures, 83 % of which included
      catheter-directed thrombolysis (CDT). However, the details of these endovascular
      procedures and their outcomes have not yet been fully evaluated. Using DVT data
      from the EDO registry (EnDOvascular treatment registry) database, a total of 35
      symptomatic iliac or femoral DVT patients who received endovascular treatment
      (54.3 % male, age 64.7 +/- 15.1) were analyzed. The dominant patient risks were
      being bedridden (22.9 %) and May-Thurner syndrome (25.7 %). Approximately 77.1 %
      of patients were treated using an antegrade approach, and CDT and other
      endovascular procedures were performed in 82.9 and 57.1 % of patients,
      respectively. A periprocedural inferior vena cava (IVC) filter was used in 94.1 %
      of patients, which remained implanted in 37.1 and 20.0 % of patients after
      discharge and 6 months after hospitalization, respectively. After 6 months of
      treatment, 2.9 % of patients experienced a recurrence of DVT and 5.7 % suffered
      revascularization, but no patient had a recurrence of pulmonary embolism.
      Subjective symptoms improved in 80.0 % of patients, while 2.9 % of patients felt
      worse at 6 months after treatment. Postthrombotic syndrome-related symptoms were
      observed in seven patients (19.4 %), and edema was most frequently observed (71.4
      %). The details of CDT procedures, such as approach site and the removal of the
      IVC filter, varied among hospitals. Despite improved symptoms, further procedural
      standardization and data collection should be conducted to reduce complications
      and improve outcomes. 

PMID- 25575650
TI  - [Macrophage activation syndrome in a patient with systemic juvenile idiopathic
      arthritis].
AB  - Machrophage activation syndrome (MAS) is a rare and potentially fatal disease,
      commonly associated with chronic rheumatic diseases, mainly juvenile idiopathic
      arthritis. It is included in the group of secondary forms of haemophagocytic
      syndrome, and other causes are lymphoproliferative diseases and infections. Its
      most important clinical and laboratorial manifestations are non-remitting fever,
      splenomegaly, bleeding, impairment of liver function, cytopenias,
      hypoalbuminemia, hypertriglyceridemia, hypofibrinogenemia and hyperferritinemia.
      The treatment needs to be started quickly, and the majority of cases have a good
      response with corticosteroids and cyclosporine. The Epstein-Barr virus is
      described as a possible trigger for many cases of MAS, especially in these
      patients in treatment with tumor necrosis factor (TNF) blockers. In these
      refractory cases, etoposide (VP16) should be administered, associated with
      corticosteroids and cyclosporine. Our objective is to describe a rare case of MAS
      probably due to EBV infection in a subject with systemic-onset juvenile
      idiopathic arthritis, which achieved complete remission of the disease after
      therapy guided by 2004-HLH protocol. 

PMID- 25575651
TI  - Quantitative analytical method to evaluate the metabolism of vitamin D.
AB  - A method for quantitative analysis of vitamin D (both D2 and D3) and its main
      metabolites - monohydroxylated vitamin D (25-hydroxyvitamin D2 and 25
      hydroxyvitamin D3) and dihydroxylated metabolites (1,25-dihydroxyvitamin D2, 1,25
      dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3) in human serum is here
      reported. The method is based on direct analysis of serum by an automated
      platform involving on-line coupling of a solid-phase extraction workstation to a
      liquid chromatograph-tandem mass spectrometer. Detection of the seven analytes
      was carried out by the selected reaction monitoring (SRM) mode, and quantitative
      analysis was supported on the use of stable isotopic labeled internal standards
      (SIL-ISs). The detection limits were between 0.3-75pg/mL for the target
      compounds, while precision (expressed as relative standard deviation) was below
      13.0% for between-day variability. The method was externally validated according
      to the vitamin D External Quality Assurance Scheme (DEQAS) through the analysis
      of ten serum samples provided by this organism. The analytical features of the
      method support its applicability in nutritional and clinical studies targeted at
      elucidating the role of vitamin D metabolism. 

PMID- 25575653
TI  - Trends in tobacco consumption in three different birth cohorts of elderly of Sao
      Paulo, Brazil.
AB  - BACKGROUND: The effects of birth cohorts reflect the historical differences in
      physical and social environments. The objectives of the present study were to
      describe the tobacco consumption and to evaluate the behavioral trends with
      respect to smoking in three different birth cohorts of a population-based sample
      of elderly individuals. METHODS: A series of three cross-sectional studies
      conducted with elderly individuals of 60-64 years of age interviewed in 2000
      (birth cohort 1936-1940; n=427), 2006 (birth cohort 1942-1946; n=298) and 2011
      (birth cohort 1947-1951; n=355) in a population-based sample from the city of Sao
      Paulo, Brazil. The interviewees were participating in a prospective cohort study
      entitled Health, Well-Being and Aging (Saude, Bem-Estar e Envelhecimento [SABE]).
      Data on tobacco consumption were self-reported and interviewees were then
      classified as never smokers, former smokers or current smokers. Linear model for
      categorical data was used to test differences on tobacco consumption between
      three birth elderly cohorts. FINDINGS: Men were more likely than women to be
      smokers. Being evangelical and having more schooling constituted protective
      factors against smoking. Regarding trends, the tobacco consumption of the men did
      not change in any of the three cohorts studied (p=0.7454), whereas there was an
      increase in the number of women smokers, principally former smokers, over the
      periods evaluated (p=0.0189). CONCLUSIONS: These results suggest that the anti
      smoking policies implemented in Brazil were effective in women of this age group;
      however, different prevention strategies are required to target elderly men.

PMID- 25575652
TI  - Mortality among older adults with opioid use disorders in the Veteran's Health
      Administration, 2000-2011.
AB  - BACKGROUND: The population of people with opioid use disorders (OUD) is aging.
      There has been little research on the effects of aging on mortality rates and
      causes of death in this group. We aimed to compare mortality in older (>= 50
      years of age) adults with OUD to that in younger (<50 years) adults with OUD and
      older adults with no history of OUD. We also examined risk factors for specific
      causes of death in older adults with OUD. METHODS: Using data from the Veteran's
      Health Administration National Patient Care Database (2000-2011), we compared all
      cause and cause-specific mortality rates in older adults with OUD to those in
      younger adults with OUD and older adults without OUD. We then generated a Cox
      regression model with specific causes of death treated as competing risks.
      RESULTS: Older adults with OUD were more likely to die from any cause than
      younger adults with OUD. The drug-related mortality rate did not decline with
      age. HIV-related and liver-related deaths were higher among older OUD compared to
      same-age peers without OUD. There were very few clinically important predictors
      of specific causes of death. CONCLUSION: Considerable drug-related mortality in
      people with OUD suggests a need for greater access to overdose prevention and
      opioid substitution therapy across the lifespan. Elevated risk of liver-related
      death in older adults may be addressed through antiviral therapy for hepatitis C
      virus infection. There is an urgent need to explore models of care that address
      the complex health needs of older adults with OUD.

PMID- 25575655
TI  - A test of the Energetics-Hormone Vocalization model in the green treefrog.
AB  - Male courtship displays may be regulated by, and affect the production of,
      circulating hormones. The Energetics-Hormone Vocalization (EHV) model, for
      example, posits that interactions among chorusing male anuran amphibians
      stimulate androgen production that then mediates an increase in vocal effort.
      Increased vocal effort is expected to deplete energy reserves and increase
      glucocorticoid levels that, in turn, negatively affect androgen levels and
      vocalization. Androgen levels, glucocorticoid levels, and vocal effort are thus
      expected to increase across and within nights of chorus activity and should be
      positively correlated in calling males; energy reserves should decline temporally
      and be inversely related to glucocorticoid levels. We tested predictions of the
      EHV model in the green treefrog, Hyla cinerea. Consistent with the model, both
      testosterone and dihydrotestosterone levels increased across the breeding season
      in calling males. However, testosterone levels decreased and dihydrotestosterone
      levels did not change within nights of chorus activity, suggesting that chorusing
      behavior did not drive the seasonal elevation in androgens. Corticosterone (CORT)
      level remained relatively stable across the breeding season and decreased within
      nights of chorus activity, contrary to model predictions. Body condition, the
      proxy for energetic state, was inversely correlated with CORT level but
      discrepancies between model predictions and temporal patterns of CORT production
      arose because there was no evidence of a temporal decrease in body condition or
      increase in vocal effort. Moreover, androgen and CORT levels were not positively
      correlated with vocal effort. Additional ecological and physiological measures
      may be needed to support predictions of the EHV model. 

PMID- 25575654
TI  - Discovery of novel inhibitors for the treatment of glaucoma.
AB  - INTRODUCTION: Glaucoma is a neurodegenerative disease with heterogeneous causes
      that result in retinal ganglionic cell (RGC) death. The discovery of ocular
      antihypertensives has shifted glaucoma therapy, largely, from surgery to medical
      intervention. Indeed, several intraocular pressure (IOP)-lowering drugs, with
      different mechanisms of action and RGC protective property, have been developed.
      AREAS COVERED: In this review, the authors discuss the main new class of kinase
      inhibitors used as glaucoma treatments, which lower IOP by enhancing drainage
      and/or lowering production of aqueous humor. The authors include novel inhibitors
      under preclinical evaluation and investigation for their anti-glaucoma treatment.
      Additionally, the authors look at treatments that are in clinics now and which
      may be available in the near future. EXPERT OPINION: Treatment of glaucoma
      remains challenging because the exact cause is yet to be delineated.
      Neuroprotection to the optic nerve head is undisputable. The novel Rho-associated
      kinase inhibitors have the capacity to lower IOP and provide optic nerve and RGC
      protection. In particular, the S-isomer of roscovitine has the capacity to lower
      IOP and provide neuroprotection. Combinations of selected drugs, which can
      provide maximal and sustained IOP-lowering effects as well as neuroprotection,
      are paramount to the prevention of glaucoma progression. In the near future,
      microRNA intervention may be considered as a potential therapeutic target.

PMID- 25575656
TI  - Aza follow-ups to BI 207524, a thumb pocket 1 HCV NS5B polymerase inhibitor. Part
      1: Mitigating the genotoxic liability of an aniline metabolite.
AB  - A series of heterocyclic aza-analogs of BI 207524 (2), a potent HCV NS5B
      polymerase thumb pocket 1 inhibitor, was investigated with the goal to reduce the
      liability associated with the release of a genotoxic aniline metabolite in vivo.
      Analog 4, containing a 2-aminopyridine aniline isostere that is negative in the
      Ames test was identified, and was found to provide comparable GT1a/1b potency to
      2. Although the cross-species PK profile, poor predicted human liver distribution
      of analog 4 and allometry principles projected high doses to achieve a strong
      antiviral response in patients, this work has provided a path forward toward the
      design of novel thumb pocket 1 NS5B polymerase inhibitors with improved safety
      profiles. 

PMID- 25575657
TI  - Structure-based design of low-nanomolar PIM kinase inhibitors.
AB  - PIM kinases are implicated in variety of cancers by promoting cell survival and
      proliferation and are targets of interest for therapeutic intervention. We have
      identified a low-nanomolar pan-PIM inhibitor (PIM1/2/3 potency 5:14:2nM) using
      structure based modeling. The crystal structure of this compound with PIM1
      confirmed the predicted binding mode and protein-ligand interactions except those
      in the acidic ribose pocket. We show the SAR suggesting the importance of having
      a hydrogen bond donor in this pocket for inhibiting PIM2; however, this
      interaction is not important for inhibiting PIM1 or PIM3. In addition, we report
      the discovery of a new class of PIM inhibitors by using computational de novo
      design tool implemented in MOE software (Chemical Computing Group). These
      inhibitors have a different interaction profile. 

PMID- 25575658
TI  - Selective CB2 receptor agonists. Part 3: the optimization of a piperidine-based
      series that demonstrated efficacy in an in vivo neuropathic pain model.
AB  - A novel class of potent cannabinoid receptor 2 (CB2) agonists based on a (S)
      piperidine scaffold was identified using ligand-based pharmacophore models.
      Optimization of solubility and metabolic stability led to the identification of
      several potent CB2 agonists (e.g., 30) that displayed selectivity over
      cannabinoid receptor 1 (CB1) and acceptable drug like properties. In rats,
      compound 30 demonstrated a favorable pharmacokinetic profile and efficacy in a
      Streptozotocin-induced diabetic neuropathy model, with full reversal of
      mechanical hyperalgesia. 

PMID- 25575659
TI  - SAR-studies of gamma-secretase modulators with PPARgamma-agonistic and 5
      lipoxygenase-inhibitory activity for Alzheimer's disease.
AB  - We present the design, synthesis and biological evaluation of compounds
      containing a 2-(benzylidene)hexanoic acid scaffold as multi-target directed gamma
      secretase-modulators. Broad structural variations were undertaken to elucidate
      the structure-activity-relationships at the 5-position of the aromatic core.
      Compound 13 showed the most potent activity profile with IC50 values of 0.79MUM
      (Abeta42), 0.3MUM (5-lipoxygenase) and an EC50 value of 4.64MUM for PPARgamma
      activation. This derivative is the first compound exhibiting low micromolar to
      nanomolar activities for these three targets. Combining gamma-secretase
      modulation, PPARgamma-agonism and inhibition of 5-lipoxygenase in one compound
      could be a novel disease-modifying multi-target-strategy for Alzheimer's disease
      to concurrently address the causative amyloid pathology and secondary pathologies
      like chronic brain inflammation. 

PMID- 25575660
TI  - Structural measurements and cell line studies of the copper-PEG-Rifampicin
      complex against Mycobacterium tuberculosis.
AB  - The bacterium responsible for tuberculosis is increasing its resistance to
      antibiotics resulting in new multidrug-resistant Mycobacterium tuberculosis (MDR
      TB) and extensively drug-resistant tuberculosis (XDR-TB). In this study, several
      analytical techniques including NMR, FT-ICR, MALDI-MS, LC-MS and UV/Vis are used
      to study the copper-Rifampicin-Polyethylene glycol (PEG-3350) complex. The copper
      (II) cation is a carrier for the antibiotic Rifampicin as well as nutrients for
      the bacterium. The NIH-NIAID cell line containing several Tb strains (including
      antibiotic resistant strains) is tested against seven copper-PEG-RIF complex
      variations. 

PMID- 25575661
TI  - A prospective study on the morbidity resulting from calvarial bone harvesting for
      intraoral reconstruction.
AB  - Calvarial bone grafts are used for reconstruction of the maxilla or mandible to
      enable implant placement. The aim of this study was to assess the morbidity
      resulting from the use of calvarial bone grafts to reconstruct the maxilla and
      mandible. Thirty-six consecutive patients were included in this prospective study
      (14 men and 22 women; mean age 59 +/- 8.2 years). Perioperative and postoperative
      complications related to harvesting of the calvarial bone were scored, as well as
      the occurrence of intraoral complications (average follow-up 25 +/- 12 months).
      Perioperative exposure of the dura occurred in four patients and the graft broke
      during harvesting in five patients. With a change in the technique, these
      complications no longer occurred. Postoperative pain levels at the calvarial
      donor site were low (visual analogue scale (VAS) 1.9 +/- 2.0 on day 1) and of
      short duration (5.2 +/- 4.7 days to becoming pain-free). In all cases sufficient
      bone could be harvested to enable the placement of implants. The exposure of the
      dura and the intraoral complications were of no clinical consequence. Therefore,
      calvarial bone grafts appear to be promising for use in pre-implant intraoral
      reconstructions.

PMID- 25575662
TI  - The distribution in tissues and urine of arsenic metabolites after subchronic
      exposure to dimethylarsinic acid (DMAV) in rats.
AB  - Dimethylarsinic acid (DMA(V)) acted as cancer promoter promoted urinary bladder,
      liver, and lung carcinogenesis in rats. Understanding of the distribution of
      arsenicals in critical sites will aid to define the action of DMA(V)-induced
      toxicity and carcinogenicity. The present experiment was conducted to compare the
      accumulated levels of arsenicals in the liver, kidney, and bladder of both male
      and female rats after subchronic exposure to DMA(V). After exposure to DMA(V) in
      drinking water for 10 weeks, urinary DMA concentrations of 100 and 200 ppm DMA(V)
      treated rats increased significantly compared with those of the control rats.
      Smaller amount of trimethylarsinic acid (TMA) was detected in urine, but not in
      liver, kidney, and bladder muscle. In the liver and kidney, the levels of DMA in
      DMA(V)-treated rats significantly increased compared with those of the control
      group, but there was no difference between 100 and 200 ppm DMA(V)-treated rats.
      DMA did not accumulate in bladder muscle. There was no difference for DMA
      concentrations between male and female rats. Our results suggest that the
      accumulation of DMA in the liver and kidney was saturated above 100 ppm DMA(V)
      treatment concentration, and DMA(V) was a little partly metabolized to TMA, and
      TMA was rapidly excreted into urine.

PMID- 25575663
TI  - Assessment of oxidative stress in hippocampus, cerebellum and frontal cortex in
      rat pups exposed to lead (Pb) during specific periods of initial brain
      development.
AB  - Epidemiological studies in children have proved that lead (Pb) exposure causes
      deficits in neural and cognitive functions. The present study assessed the
      oxidative stress on postnatal day 30, in the hippocampus, cerebellum and frontal
      cortex of rat pups exposed to Pb during specific periods of early brain
      development. Five groups of rat pups were investigated, and 0.2% Pb acetate in
      drinking was the dosage used. (i) Gestation and lactation (GL) group (n = 9) of
      rat pups was exposed to Pb during gestation and lactation through their mother,
      (ii) gestation (G) group (n = 9) of rat pups was exposed to Pb during gestation
      only, (iii) lactation (L) group (n = 9) of rat pups was exposed to Pb during
      lactation only, (iv) pre-gestation (PG) group (n = 9) of rat pups was born to
      mothers who were exposed to Pb for 1 month before conception, and (v) normal
      control (NC) (n = 9) group of rats pups had no exposure to Pb during gestation
      and lactation period. From the present study, it is evident that Pb exposure
      during different periods of early brain development (GL, G, L and PG groups)
      causes oxidative stress and lactation period (postnatal period) of Pb exposure
      produces maximum oxidative stress.

PMID- 25575664
TI  - Effects of methionine chelate- or yeast proteinate-based supplement of copper,
      iron, manganese and zinc on broiler growth performance, their distribution in the
      tibia and excretion into the environment.
AB  - A straight-run flock of 1-day-old Cobb 400 chicks (n = 432) was distributed into
      four treatment groups (9 replicate pens in each group, 12 birds in a pen) for a
      38-day feeding trial evaluating the effects of a methionine chelate (Met-TM)- or
      a yeast proteinate (Yeast-TM)-based supplement of copper (Cu), iron (Fe),
      manganese (Mn) and zinc (Zn) on growth performance, bone criteria and some
      metabolic indices in commercial broiler chickens. The diets were either not
      supplemented with any trace elements at all (negative control, NC) or
      supplemented with an inorganic (sulphate) trace element premix (inorganic TM
      (ITM), 1 g/kg feed), the Met-TM (1 g/kg feed) and the Yeast-TM (0.5 g/kg feed).
      Body weight, feed conversion ratio and dressed meat yield at 38 days were better
      in the Yeast-TM-supplemented group as compared with the NC, ITM and Met-TM groups
      (p < 0.01). The birds supplemented with Met-TM and Yeast-TM consumed less feed
      than the NC and ITM-supplemented group (p < 0.001). Supplementation of trace
      elements irrespective of source increased the total ash content in the tibia (p <
      0.001). However, concentration of Cu was lower in the Met-TM and Yeast-TM groups
      compared with the NC and the ITM groups (p < 0.05) although that of Fe, Mn and Zn
      was not affected at all by the dietary treatments. Total protein concentration in
      serum increased when either Met-TM or Yeast-TM was supplemented (p < 0.05) to the
      birds. Serum alkaline phosphatase activity, however, increased when the trace
      elements from either inorganic or organic sources were supplemented (p < 0.05).
      Compared with the ITM-supplemented group, excretion of Cu, Fe, Mn and Zn was
      lower in the birds supplemented with Met-TM or Yeast-TM, especially in the latter
      group (p < 0.05). The present experiment revealed that supplementation of
      broilers with methionine chelates or yeast proteinate forms of Cu, Fe, Mn and Zn
      improved body weight and feed conversion ratio (FCR) and markedly reduced
      excretion of the said trace elements. The study revealed that it may be possible
      to improve broiler performance and reduce excretion of critical trace elements
      into the environment by complete replacement of inorganic trace minerals from
      their dietary regime and replacing the same with methionine chelate or yeast
      proteinate forms.

PMID- 25575665
TI  - Increased DNA damage and oxidative stress among silver jewelry workers.
AB  - Silver has long been valued as a precious metal, and it is used to make
      ornaments, jewelry, high-value tableware, utensils, and currency coins. Human
      exposures to silver and silver compounds can occur oral, dermal, or by
      inhalation. In this study, we investigated genotoxic and oxidative effects of
      silver exposure among silver jewelry workers. DNA damage in peripheral
      mononuclear leukocytes was measured by using the comet assay. Serum total
      antioxidative status (TAS), total oxidative status (TOS), total thiol contents,
      and ceruloplasmin levels were measured by using colorimetric methods among silver
      jewelry workers. Moreover, oxidative stress index (OSI) was calculated. Results
      were compared with non-exposed healthy subjects. The mean values of mononuclear
      leukocyte DNA damage were significantly higher than control subjects (p < 0.001).
      Serum TOS, OSI, and ceruloplasmin levels were also found to be higher in silver
      particles exposed group than those of non-exposed group (p < 0.001, p < 0.001, p
      < 0.01, respectively). However, serum TAS levels and total thiol contents of
      silver exposed group were found significantly lower (p < 0.05, p < 0.001,
      respectively). Exposure to silver particles among silver jewelry workers caused
      oxidative stress and accumulation of severe DNA damage.

PMID- 25575666
TI  - Analysis of blood trace elements and biochemical indexes levels in severe
      craniocerebral trauma adults with Glasgow Coma Scale and injury severity score.
AB  - We aimed to investigate the correlation between the Glasgow Coma Scale (GCS), the
      injury severity score (ISS) and serum levels of trace elements (TE) in severe
      trauma patients to analyze alteration of the levels of trace elements and serum
      biochemical indexes in the period of admission from 126 adult cases of severe
      brain trauma with traffic accidents. Multi-trace elements for patients in the
      trauma-TE groups were used. The results indicated that all patients presented an
      acute trace elements deficiency syndrome (ATEDs) after severe trauma, and the
      correlation between ISS and serum levels of Fe, Zn, and Mg was significant.
      Compared to the normal control group, levels of the trace elements in serum were
      significantly decreased after trauma, suggesting that enhancement of immunity to
      infection and multiple organ failure (MOF) via the monitoring and supplement of
      trace elements will be a good strategy to severe traumatic patients in clinics. 

PMID- 25575667
TI  - Retarded PDI diffusion and a reductive shift in poise of the calcium depleted
      endoplasmic reticulum.
AB  - BACKGROUND: Endoplasmic reticulum (ER) lumenal protein thiol redox balance
      resists dramatic variation in unfolded protein load imposed by diverse
      physiological challenges including compromise in the key upstream oxidases.
      Lumenal calcium depletion, incurred during normal cell signaling, stands out as a
      notable exception to this resilience, promoting a rapid and reversible shift
      towards a more reducing poise. Calcium depletion induced ER redox alterations are
      relevant to physiological conditions associated with calcium signaling, such as
      the response of pancreatic cells to secretagogues and neuronal activity. The core
      components of the ER redox machinery are well characterized; however, the
      molecular basis for the calcium-depletion induced shift in redox balance is
      presently obscure. RESULTS: In vitro, the core machinery for generating
      disulfides, consisting of ERO1 and the oxidizing protein disulfide isomerase,
      PDI1A, was indifferent to variation in calcium concentration within the
      physiological range. However, ER calcium depletion in vivo led to a selective 2.5
      fold decline in PDI1A mobility, whereas the mobility of the reducing PDI family
      member, ERdj5 was unaffected. In vivo, fluorescence resonance energy transfer
      measurements revealed that declining PDI1A mobility correlated with formation of
      a complex with the abundant ER chaperone calreticulin, whose mobility was also
      inhibited by calcium depletion and the calcium depletion-mediated reductive shift
      was attenuated in cells lacking calreticulin. Measurements with purified proteins
      confirmed that the PDI1A-calreticulin complex dissociated as Ca(2+)
      concentrations approached those normally found in the ER lumen ([Ca(2+)]K(0.5max)
      = 190 MUM). CONCLUSIONS: Our findings suggest that selective sequestration of
      PDI1A in a calcium depletion-mediated complex with the abundant chaperone
      calreticulin attenuates the effective concentration of this major lumenal thiol
      oxidant, providing a plausible and simple mechanism for the observed shift in ER
      lumenal redox poise upon physiological calcium depletion.

PMID- 25575668
TI  - Adolescent rats are resistant to forming ethanol seeking habits.
AB  - Early age of onset alcohol drinking is significantly more likely to lead to
      alcohol use disorders (AUDs) than alcohol drinking that begins after the age of
      18. Unfortunately, the majority of people in the United States begin drinking in
      adolescence. Therefore, it is important to understand how early alcohol drinking
      leads to increased risk for AUDs so that better treatments and prevention
      strategies can be developed. Adolescents perceive greater rewarding properties of
      alcohol, and adolescents may be more likely to form alcohol-seeking habits that
      promote continued use throughout the lifetime. Therefore, we compared the
      development of alcohol seeking habits in adolescent and adult male, Sprague
      Dawley rats. Rats were trained to lever press to receive 10% ethanol+0.1%
      saccharin on a schedule that promotes habit formation. Rats were tested using a
      contingency degradation procedure at different points in training. Adult rats
      formed ethanol-seeking habits with only moderate training, while adolescents
      remained goal-directed even with extended training. Nevertheless, adolescents
      consumed more ethanol than adults throughout the experiment and continued to
      consume more ethanol than adults when they reached adulthood. Therefore, early
      onset alcohol use may promote AUD formation through establishment of high levels
      of drinking that becomes habitual in adulthood.

PMID- 25575669
TI  - Functional characterization of an anthocyanidin reductase gene from the fibers of
      upland cotton (Gossypium hirsutum).
AB  - MAIN CONCLUSION: Metabolic profiling, gene cloning, enzymatic analysis, ectopic
      expression, and gene silencing experiments demonstrate that the anthocyanidin
      reductase (ANR) pathway is involved in the biosynthesis of proanthocyanidins in
      upland cotton. Proanthocyanidins (PAs) are oligomeric or polymeric flavan-3-ols,
      however, the biosynthetic pathway of PAs in cotton remains to be elucidated.
      Here, we report on an anthocyanidin reductase (ANR) gene from cotton fibers and
      the ANR pathway of PAs. Phytochemical analysis demonstrated that leaves, stems,
      roots, and early developing fibers produced PAs and their monomers, including (-)
      epicatechin, (-)-catechin, (-)-epigallocatechin, and (-)-gallocatechin. Crude PA
      extractions from different tissues were boiled in Butanol:HCl. Cyanidin,
      delphinidin, and pelargonidin were produced, indicating that cotton PAs include
      diverse extension unit structures. An ANR cDNA homolog (named GhANR1) was cloned
      from developing fibers. The open reading frame, composed of 1,011 bp nucleotides,
      was expressed in E. coli to obtain a recombinant protein. In the presence of
      NADPH, the recombinant enzyme catalyzed cyanidin, delphinidin, and pelargonidin
      to (-)-epicatechin and (-)-catechin, (-)-epigallocatechin and (-)-gallocatechin,
      and (-)-epiafzelechin and (-)-afzelechin, respectively. The ectopic expression of
      GhANR11 in an Arabidopsis ban mutant allowed for the reconstruction of the ANR
      pathway and PA biosynthesis in the seed coat. Virus-induced gene silencing (VIGS)
      of GhANR11 led to a significant increase in anthocyanins and a decrease in the
      PAs, (-)-epicatechin, and (-)-catechin in the stems and leaves of VIGS-infected
      plants. Taken together, these data demonstrate that the ANR pathway contributes
      to the biosynthesis of flavan-3-ols and PAs in cotton.

PMID- 25575670
TI  - Topographic anatomy of the ulnar tunnel.
AB  - PURPOSE: The aim of this study was to clarify the definition of the anterior wall
      of the ulnar tunnel and to reveal the topographical characteristics of the
      various components of the ulnar tunnel. MATERIALS AND METHODS: Twenty-two
      forearms from 11 embalmed cadavers (7 males, 4 females; mean age, 67.8 years)
      were carefully dissected. RESULTS: In all cases, the anterior wall of the ulnar
      tunnel comprised the hypothenar fascia, which originated from the tendon of the
      flexor carpi ulnaris muscle. The palmar carpal ligament, the distal extent of the
      antebrachial fascia, was located deep to the anterior wall and formed only the
      anterior boundary of the proximal hiatus of the ulnar tunnel. The hypothenar
      fascia was attached to the flexor retinaculum at 15.2 mm lateral to the pisiform
      bone. However, the palmar carpal ligament was attached to the flexor retinaculum
      just lateral to the ulnar artery; the distance between the attachment of the
      palmar carpal ligament and the pisiform bone was 8.7 mm. Anatomical variations
      potentially associated with ulnar nerve compression were observed. The accessory
      abductor digiti minimi muscle and the fibrous band crossing the ulnar nerve in
      the ulnar tunnel were found in 27 and 23 % of forearms, respectively. CONCLUSION:
      A more detailed description of the anterior wall of the ulnar tunnel than was
      previously available is presented herein, and topographic and metric data
      regarding each structure of the tunnel are reported.

PMID- 25575672
TI  - The impact of a temporary recurrent street closure on physical activity in New
      York City.
AB  - At least 70 US cities have now introduced ciclovias-large-scale street closures
      to promote physical activity-joining numerous other cities worldwide that have
      implemented ciclovias in efforts to improve population health. We assessed the
      impact of Summer Streets, a New York City program in which 6.9 contiguous miles
      of urban streets were closed to traffic and opened for walking, cycling, and
      group activities, such as dancing and yoga, on population physical activity
      levels. Screen line counts were used to estimate attendance, and a street
      intercept survey was conducted to assess demographic characteristics of
      participants, baseline adherence to physical activity recommendations, and type
      and duration of physical activity at Summer Streets. In addition, a traffic study
      was used to determine if there were vehicular traffic delays as a result of the
      program. About 50,000 people participated in Summer Streets; among participating
      New Yorkers, bicyclists averaged 6.7 miles, runners 4.3 miles, and walkers 3.6
      miles, equivalent to 72-86 min of moderate physical activity. Among New Yorkers
      attending Summer Streets, 24 % reported that they did not routinely engage in
      moderate- or vigorous-intensity physical activity. These non-routine exercisers
      engaged in the equivalent of 26-68 min of moderate-intensity physical activity at
      Summer Streets. Summer Streets served as an enticement for New Yorkers, including
      those who did not ordinarily meet physical activity recommendations, to engage in
      physical activity. There were no significant vehicular traffic delays during the
      program.

PMID- 25575673
TI  - The interactions between temperature and activity levels in driving metabolic
      rate: theory, with empirical validation from contrasting ectotherms.
AB  - The rate of change in resting metabolic rate (RMR) as a result of a temperature
      increase of 10  degrees C is termed the temperature coefficient (Q10), which is
      often used to predict how an organism's total MR will change with temperature.
      However, this method neglects a potentially key component of MR; changes in
      activity level (and thus activity MR; AMR) with temperature may significantly
      alter the relationship between MR and temperature. The present study seeks to
      describe how thermal effects on total MR estimated from RMR-temperature
      measurements can be misleading when the contribution of activity to total MR is
      neglected. A simple conceptual framework illustrates that since the relationship
      between activity levels and temperature can be different to the relationship
      between RMR and temperature, a consistent relationship between RMR and total MR
      cannot be assumed. Thus the thermal effect on total MR can be considerably
      different to the thermal effect on RMR. Simultaneously measured MR and activity
      from three ectotherm species with differing behavioural and physiological
      ecologies were used to empirically examine how changes in temperature drive
      changes in RMR, activity level, AMR and the Q10 of MR. These species exhibited
      varied activity- and MR-temperature relationships, underlining the difficulty in
      predicting thermal influences on activity levels and total MR. These data support
      a model showing that thermal effects on total MR will deviate from predictions
      based solely on RMR; this deviation will depend upon the difference in Q10
      between AMR and RMR, and the relative contribution of AMR to total MR. To develop
      mechanistic, predictive models for species' metabolic responses to temperature
      changes, empirical information about the relationships between activity levels,
      MR and temperature, such as reported here, is required. This will supersede
      predictions based on RMR alone.

PMID- 25575674
TI  - An ant-plant by-product mutualism is robust to selective logging of rain forest
      and conversion to oil palm plantation.
AB  - Anthropogenic disturbance and the spread of non-native species disrupt natural
      communities, but also create novel interactions between species. By-product
      mutualisms, in which benefits accrue as side effects of partner behaviour or
      morphology, are often non-specific and hence may persist in novel ecosystems. We
      tested this hypothesis for a two-way by-product mutualism between epiphytic ferns
      and their ant inhabitants in the Bornean rain forest, in which ants gain housing
      in root-masses while ferns gain protection from herbivores. Specifically, we
      assessed how the specificity (overlap between fern and ground-dwelling ants) and
      the benefits of this interaction are altered by selective logging and conversion
      to an oil palm plantation habitat. We found that despite the high turnover of ant
      species, ant protection against herbivores persisted in modified habitats.
      However, in ferns growing in the oil palm plantation, ant occupancy, abundance
      and species richness declined, potentially due to the harsher microclimate. The
      specificity of the fern-ant interactions was also lower in the oil palm
      plantation habitat than in the forest habitats. We found no correlations between
      colony size and fern size in modified habitats, and hence no evidence for partner
      fidelity feedbacks, in which ants are incentivised to protect fern hosts. Per
      species, non-native ant species in the oil palm plantation habitat (18 % of
      occurrences) were as important as native ones in terms of fern protection and
      contributed to an increase in ant abundance and species richness with fern size.
      We conclude that this by-product mutualism persists in logged forest and oil palm
      plantation habitats, with no detectable shift in partner benefits. Such
      persistence of generalist interactions in novel ecosystems may be important for
      driving ecosystem functioning.

PMID- 25575675
TI  - Butyrylcholinesterase genotype and enzyme activity in relation to Gulf War
      illness: preliminary evidence of gene-exposure interaction from a case-control
      study of 1991 Gulf War veterans.
AB  - BACKGROUND: Epidemiologic studies have implicated wartime exposures to
      acetylcholinesterase (AChE)-inhibiting chemicals as etiologic factors in Gulf War
      illness (GWI), the multisymptom condition linked to military service in the 1991
      Gulf War. It is unclear, however, why some veterans developed GWI while others
      with similar exposures did not. Genetic variants of the enzyme
      butyrylcholinesterase (BChE) differ in their capacity for metabolizing AChE
      inhibiting chemicals, and may confer differences in biological responses to these
      compounds. The current study assessed BChE enzyme activity and BChE genotype in
      1991 Gulf War veterans to evaluate possible association of this enzyme with GWI.
      METHODS: This case-control study evaluated a population-based sample of 304 Gulf
      War veterans (144 GWI cases, meeting Kansas GWI criteria, and 160 controls). BChE
      enzyme activity levels and genotype were compared, overall, in GWI cases and
      controls. Potential differences in risk associated with cholinergic-related
      exposures in theater were explored using stratified analyses to compare
      associations between GWI and exposures in BChE genetic and enzyme activity
      subgroups. RESULTS: Overall, GWI cases and controls did not differ by mean BChE
      enzyme activity level or by BChE genotype. However, for the subgroup of Gulf War
      veterans with less common, generally less active, BChE genotypes (K/K, U/AK, U/A,
      A/F, AK/F), the association of wartime use of pyridostigmine bromide (PB) with
      GWI (OR=40.00, p=0.0005) was significantly greater than for veterans with the
      more common U/U and U/K genotypes (OR=2.68, p=0.0001). CONCLUSIONS: Study results
      provide preliminary evidence that military personnel with certain BChE genotypes
      who used PB during the 1991 Gulf War may have been at particularly high risk for
      developing GWI. Genetic differences in response to wartime exposures are
      potentially important factors in GWI etiology and should be further evaluated in
      conjunction with exposure effects.

PMID- 25575676
TI  - Nano-Mg(OH)2-induced proliferation inhibition and dysfunction of human umbilical
      vein vascular endothelial cells through caveolin-1-mediated endocytosis.
AB  - Nano-Mg(OH)2 is efficiently used in pollutant adsorption and removal due to its
      high adsorption capability, low-cost, and recyclability. A recent research from
      our group showed that Mg(OH)2 nanoflakes are not evidently internalized by cancer
      cells and are not cytotoxic. But the biocompatibility and potential toxicity of
      nano-Mg(OH)2 in a normal biological system are largely unclear. Nanoparticles
      could affect the function of endothelial cells, and endothelial dysfunction
      represents an early sign of lesion within the vasculature. Here, we applied the
      human umbilical vein vascular endothelial cells (HUVECs) as an in vitro model of
      the endothelium to study the cytotoxicity of nano-Mg(OH)2. Our results showed
      that nano-Mg(OH)2 at 200 MUg/ml impaired proliferation and induced dysfunction of
      HUVECs, but did not result in cell necrosis and apoptosis. Transmission electron
      microscopy images and immunofluorescence results showed that the nano-Mg(OH)2
      could enter HUVECs through caveolin-1-mediated endocytosis. Nano-Mg(OH)2 at high
      concentrations decreased the level of caveolin-1 and increased the activity of
      endothelial nitric oxide synthase (eNOS), thus leading to the production of
      excess nitric oxide (NO). In this work, we provide the cell damage concentrations
      of nano-Mg(OH)2 nanoparticles, and we propose a mechanism of injury induced by
      nano-Mg(OH)2 in HUVECs. 

PMID- 25575677
TI  - Significant Association Between Fc Receptor-Like 3 Polymorphisms (-1901A>G and 
      658C>T) and Neuromyelitis Optica (NMO) Susceptibility in the Chinese Population.
AB  - Neuromyelitis optica (NMO) is an autoimmune disorder. In pathogenesis, NMO
      immunoglobulin G (NMO-IgG) selectively binds to aquaporin-4 (AQP4) and resulted
      in neuritis, myelitis, and brain lesion. Fc receptor-like 3 (FCRL3) gene encodes
      a member of the immunoglobulin receptor superfamily, which plays an important
      part in regulating immune activities. This study aimed at investigating the
      association between FCRL3 polymorphisms and NMO susceptibility and, hopefully, to
      contribute to the development of novel methods for diagnosis and treatment of
      NMO. We selected 150 NMO patients and 300 healthy controls from the Chinese
      population. Tag single nucleotide polymorphisms (SNPs) were identified with
      reference to CBI-dbSNP and HapMap databases. DNA were extracted and amplified.
      Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS) was applied to determine the polymorphisms. chi (2), odds ratio
      (OR), and 95 % confidence interval (95 % CI) were presented to evaluate genotype
      distribution and association between SNPs and NMO susceptibility. Six out of 15
      SNPs were selected according to the filter. No significant altered genotype
      distribution was observed concerning -11G>C, -166C>T, -219G>C, and -1629C>G
      polymorphisms. The G allele of -1901A>G variation was demonstrated to be more
      frequent in patients compared with controls (P < 0.001). The T allele of -658C>T
      polymorphism was significantly more prevalent in NMO patients than controls (P =
      0.009). In summary, the study revealed that the G allele in -1901A>G polymorphism
      and T allele in -658C>T polymorphism are genetic risk factors for NMO in the
      Chinese population. Further research is needed to account for different
      ethnicities and clarify the mechanisms behind, which might contribute to the
      elucidation of novel diagnosis methods.

PMID- 25575678
TI  - SIL1 Rescued Bip Elevation-Related Tau Hyperphosphorylation in ER Stress.
AB  - Endoplasmic reticulum (ER) stress has been indicated in the early stage of
      Alzheimer's disease (AD), in which tau hyperphosphorylation is one major
      pathological alteration. The elevation of binding immunoglobulin protein (Bip),
      an important ER chaperon, was reported in AD brain. It is important to study the
      roles of ER-related chaperons in tau hyperphosphorylation. In this research,
      increased Bip was found in the brains of the AD model mice (Tg2576) compared to
      the age-matched control mice. Meanwhile, deficiency of SIL1, an important co
      chaperon of Bip, was observed in brains of Tg2576 mice and in ER stress both in
      vivo and in vitro. Then, we transfected Bip-EGFP plasmid into HEK293 cells stably
      expressing the longest human tau (HEK293/tau) or N2a cells and found that
      increased Bip induced tau hyperphosphorylation via activating glycogen synthase
      kinase-3beta (GSK-3beta), an important tau kinase, and increased the association
      with tau and GSK-3beta. When we overexpressed SIL1 in Bip-transfected HEK293/tau
      cells and thapsigargin-treated HEK293/tau cells, significantly reduced tau
      hyperphosphorylation and GSK-3beta activation were observed. These results
      suggested the important roles of ER-related chaperons, Bip and SIL1, in AD-like
      tau hyperphosphorylation. 

PMID- 25575679
TI  - Sodium Channel Voltage-Gated Beta 2 Plays a Vital Role in Brain Aging Associated
      with Synaptic Plasticity and Expression of COX5A and FGF-2.
AB  - The role of sodium channel voltage-gated beta 2 (SCN2B) in brain aging is largely
      unknown. The present study was therefore designed to determine the role of SCN2B
      in brain aging by using the senescence-accelerated mice prone 8 (SAMP8), a brain
      senescence-accelerated animal model, together with the SCN2B transgenic mice. The
      results showed that SAMP8 exhibited impaired learning and memory functions,
      assessed by the Morris water maze test, as early as 8 months of age. The
      messenger RNA (mRNA) and protein expressions of SCN2B were also upregulated in
      the prefrontal cortex at this age. Treatment with traditional Chinese anti-aging
      medicine Xueshuangtong (Panax notoginseng saponins, PNS) significantly reversed
      the SCN2B expressions in the prefrontal cortex, resulting in improved learning
      and memory. Moreover, SCN2B knockdown transgenic mice were generated and bred to
      determine the roles of SCN2B in brain senescence. A reduction in the SCN2B level
      by 60.68% resulted in improvement in the hippocampus-dependent spatial
      recognition memory and long-term potential (LTP) slope of field excitatory
      postsynaptic potential (fEPSP), followed by an upregulation of COX5A mRNA levels
      and downregulation of fibroblast growth factor-2 (FGF-2) mRNA expression.
      Together, the present findings indicated that SCN2B could play an important role
      in the aging-related cognitive deterioration, which is associated with the
      regulations of COX5A and FGF-2. These findings could provide the potential
      strategy of candidate target to develop antisenescence drugs for the treatment of
      brain aging.

PMID- 25575680
TI  - Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration.
AB  - Fenpropathrin is one of the widely used pyrethroids in agriculture and household
      and also reported to have neurotoxic effects in rodent models. In our Parkinson's
      disease (PD) clinic, there was a unique patient with a history of daily exposure
      to fenpropathrin for 6 months prior to developing Parkinsonian symptoms
      progressively. Since whether fenpropathrin is related to any dopaminergic
      degeneration was unknown, we aimed in this study to evaluate the neurotoxic
      effects of fenpropathrin on the dopaminergic system and associated mechanisms in
      vitro and in vivo. In cultured SH-SY5Y cells, fenpropathrin caused cell death,
      reactive oxygen species generation, Lewy body-associated proteins aggregation,
      and Lewy body-like intracytoplasmic inclusions formation. In rodent animals, two
      different injections of fenpropathrin were used for administrations,
      intraperitoneal (i.p), or stereotaxical (ST). The rats exhibited lower number of
      pokes 60 days after first i.p injection, while the rats in ST group showed a
      significant upregulation of apomorphine-evoked rotations 60 days after first
      injection. Decreased tyrosine hydroxylase (TH) and vesicular monoamine
      transporter 2 (VMAT2) immunoreactivity, while increased dopamine transporter
      (DAT) immunoreactivity were observed in rats of either i.p or ST group 60 days
      after the last exposure to fenpropathrin. However, the number of TH-positive
      cells in the substantia nigra was more reduced 120 days after the first i.p
      injection than those of 60 days. Our data demonstrated that exposure to
      fenpropathrin could mimic the pathologic and pathogenetic features of PD
      especially in late onset cases. These results imply fenpropathrin as a DA
      neurotoxin and a possible environmental risk factor for PD.

PMID- 25575681
TI  - Developmental and Functional Brain Impairment in Offspring from Preeclampsia-Like
      Rats.
AB  - Preeclampsia is associated with developmental delay in infants and with an
      increased risk of various diseases in adulthood, including hypertension and
      epilepsy. It has been reported that several organs show developmental retardation
      and functional deficiency in offspring of preeclamptic rats. However, the
      developmental and functional changes in brains of the offspring of preeclamptic
      rats remain unknown. Here, we established a preeclampsia-like rat model induced
      using Nomega-nitro-L-arginine methyl ester (L-NAME) to analyze the developmental
      and functional changes in brains of the offspring. Body and brain weights were
      decreased in the L-NAME group at postnatal day 0 (P0). However, there were no
      significant differences between the L-NAME and control groups in brain and body
      weights at P56. Upon further analysis, we detected a deficiency in neurogenesis,
      but not in apoptosis, which contributed to the smaller brains of the offspring in
      the L-NAME group at P0. Additionally, we observed an increase in gliogenesis to
      compensate for the brain weights of the offspring at P56. Although the weight and
      laminar structure of the brains were essentially normal at P56, spatial learning
      and memory were severely impaired. We also found that adult hippocampal
      neurogenesis was disrupted in the offspring from preeclampsia-like rats, which
      may explain the cognitive deficiency. Moreover, qRT-PCR revealed a reduced
      expression of neurogenesis-related genes in the offspring. Overall, we have
      described the deleterious effects of preeclampsia on the brains of offspring,
      providing clues to the cellular and molecular mechanisms involved in this
      pathogenesis, which may aid in the development of therapeutic approaches. 

PMID- 25575682
TI  - Cypermethrin Stimulates GSK3beta-Dependent Abeta and p-tau Proteins and Cognitive
      Loss in Young Rats: Reduced HB-EGF Signaling and Downstream Neuroinflammation as
      Critical Regulators.
AB  - Pesticide exposure is recognized as a risk factor for Alzheimer's disease (AD).
      We investigated early signs of AD-like pathology upon exposure to a pyrethroid
      pesticide, cypermethrin, reported to impair neurodevelopment. We treated weanling
      rats with cypermethrin (10 and 25 mg/kg) and detected dose-dependent increase in
      the key proteins of AD, amyloid beta (Abeta), and phospho-tau, in frontal cortex
      and hippocampus as early as postnatal day 45. Upregulation of Abeta pathway
      involved an increase in amyloid precursor protein (APP) and its pro-amyloidogenic
      processing through beta-secretase (BACE) and gamma-secretase. Tau pathway
      entailed elevation in tau and glycogen-synthase kinase-3-beta (GSK3beta)
      dependent, phospho-tau. GSK3beta emerged as a molecular link between the two
      pathways, evident from reduction in phospho-tau as well as BACE upon treating
      GSK3beta inhibitor, lithium chloride. Exploring the mechanism revealed an
      attenuated heparin-binding epidermal growth factor (HB-EGF) signaling and
      downstream astrogliosis-mediated neuroinflammation to be responsible for inducing
      Abeta and phospho-tau. Cypermethrin caused a proximal reduction in HB-EGF, which
      promoted astrocytic nuclear factor kappa B signaling and astroglial activation
      close to Abeta and phospho-tau. Glial activation stimulated generation of
      interleukin-1 (IL-1), which upregulated GSK3beta, and APP and tau as well,
      resulting in co-localization of Abeta and phospho-tau with IL-1 receptor.
      Intracerebral insertion of exogenous HB-EGF restored its own signaling and
      suppressed neuroinflammation and thereby Abeta and phospho-tau in cypermethrin
      exposed rats, proving a central role of reduced HB-EGF signaling in cypermethrin
      mediated neurodegeneration. Furthermore, cypermethrin stimulated cognitive
      impairments, which could be prevented by exogenous HB-EGF. Our data demonstrate
      that cypermethrin induces premature upregulation of GSK3beta-dependent Abeta and
      tau pathways, where HB-EGF signaling and neuroinflammation serve as essential
      regulators.

PMID- 25575684
TI  - Researchers say they will send unpublished alteplase data to UK drug regulator on
      request.

PMID- 25575683
TI  - Migration and Phagocytic Ability of Activated Microglia During Post-natal
      Development is Mediated by Calcium-Dependent Purinergic Signalling.
AB  - Microglia play an important role in synaptic pruning and controlled phagocytosis
      of neuronal cells during developmental stages. However, the mechanisms that
      regulate these functions are not completely understood. The present study was
      designed to investigate the role of purinergic signalling in microglial migration
      and phagocytic activity during post-natal brain development. One-day-old BALB/c
      mice received lipopolysaccharide (LPS) and/or a purinergic analogue (2
      methylthioladenosine-5'-diphosphate; 2MeSADP), intracerebroventrically (i.c.v.).
      Combined administration of LPS and 2MeSADP resulted in activation of microglia as
      evident from increased expression of ionised calcium-binding adapter molecule 1
      (Iba1). Activated microglia showed increased expression of purinergic receptors
      (P2Y2, P2Y6 and P2Y12). LPS either alone or in combination with 2MeSADP induced
      the expression of Na(+)/Ca(2+) exchanger (NCX-1) and P/Q-type Ca(2+) channels
      along with MARCKS-related protein (MRP), which is an integral component of cell
      migration machinery. In addition, LPS and 2MeSADP administration induced the
      expression of microglial CD11b and DAP12 (DNAX-activation protein 12), which are
      known to be involved in phagocytosis of neurons during development.
      Interestingly, administration of thapsigargin (TG), a specific Ca(2+)-ATPase
      inhibitor of endoplasmic reticulum, prevented the LPS/2MeSADP-induced microglial
      activation and migration by down-regulating the expression of Iba1 and MRP,
      respectively. Moreover, TG also reduced the LPS/2MeSADP-induced expression of
      CD11b/DAP12. Taken together, the findings reveal for the first time that Ca(2+)
      mediated purinergic receptors regulate the migration and phagocytic ability of
      microglia during post-natal brain development. 

PMID- 25575685
TI  - The effects of point pollutants-originated heavy metals (lead, copper, iron, and
      cadmium) on fish living in Yesilirmak River, Turkey.
AB  - In this study, the association between heavy metals in water and cyprinids
      sampled from the Yesilirmak River stretch, which is frequently exposed to
      pollutant sources (a sugar production factory (Turhal) and solid wastes dump area
      (Tasliciftlik) was explored, and the oxidative effects of heavy metals on
      cyprinids were evaluated through analyzing some liver enzymes, namely, superoxide
      dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and cortisol. The heavy
      metal concentrations of both fish and water, collected from three different
      locations along the river during the summer of 2011 and winter of 2010 (Turhal,
      Tasliciftlik, and Gumenek), were determined by inductively coupled plasma atomic
      emission spectroscopy (ICP-AES). The water and fish liver heavy metal
      concentrations exhibited increasing trends from upstream (Gumenek) to downstream
      (Turhal). The water and liver samples collected during the summer had higher
      heavy metal concentrations than those obtained during the winter. The mean heavy
      metal concentrations increased from Gumenek to Turhal. The liver heavy metal
      concentrations were higher than those in the water and exhibited almost the same
      increasing trend from Gumenek to Turhal. Positive relationships between liver and
      water heavy metal concentrations, especially for cadmium (R 2 = 0.91) and lead (R
      2 = 0.98), were obtained. Among the liver enzymes, only MDA followed the same
      increasing trend from Gumenek to Turhal as was obtained for heavy metals. On the
      other hand, CAT and SOD had a contrary spatial pattern of change to those of
      heavy metals and MDA. Although the values of heavy metals and MDA in Tasliciftlik
      were between the two other locations, fish inhabiting this locality had
      significantly higher values of cortisol, which is an indication of the other
      stress-causing factors for fish.

PMID- 25575686
TI  - Older persons' narrations on falls and falling-stories of courage and endurance.
AB  - Fall related injuries in nursing homes have a major impact on the quality of life
      in later adulthood and there is a dearth of studies on falling and fall
      prevention from the older person's perspective. The aim of the study was to
      identify how older persons perceive falling, fall prevention, and fall accidents.
      Six in-depth interviews were carried out and a hermeneutic phenomenological
      method was used to describe and interpret the older persons' accounts.
      Interpretations of Levinasian and Heidegarian philosophy related to dwelling and
      mobility helped cultivate important insights. Symbolic and physical environments
      are important for the participants' well-being. The older persons in the study
      did not wish to dwell on the subject of falling and spoke of past and present
      coping strategies and the importance of staying on their feet. The women spoke
      about endurance in their daily lives. The men's narrations were more dramatic;
      they became animated when they spoke of their active past lives. As the scope of
      the study is small, these gender differences require further investigation.
      However, their stories give specific knowledge about the individual and their
      symbolic environmental circumstances and universal knowledge about the importance
      of integrating cultural environmental knowledge in health promotion and care
      work. Traditional fall prevention interventions are often risk oriented and based
      on generalized knowledge applied to particular cases. The findings indicate a
      need for contextual life-world knowledge and an understanding of fall prevention
      as a piece in a larger puzzle within a broader framework of culture, health, and
      well-being. Showing an interest in the older persons' stories can help safeguard
      their integrity and promote their well-being. This can ignite a spark that
      kindles their desire to participate in meaningful exercises and activities. 

PMID- 25575687
TI  - Impact of a Performance Improvement CME activity on the care and treatment of
      patients with psoriasis.
AB  - BACKGROUND: The Performance Improvement (PI) CME format improves physician
      performance in other specialties but data are lacking in dermatology. OBJECTIVE:
      We sought to assess the impact of a PI CME activity on physician practice
      patterns for patients with psoriasis, which was developed, implemented, and
      evaluated by the American Academy of Dermatology (AAD), in part to assist
      dermatologists in fulfilling Part IV of their Maintenance of Certification
      requirements. METHODS: In this PI CME activity, participants: (1) self-audited
      patient charts, which met inclusion criteria in stage A, and reflected on their
      results, benchmarked against peers; (2) reviewed educational materials in stage B
      and developed an improvement plan; and (3) self-audited a different set of
      patient charts following the plan's implementation. Aggregate stage A and C data
      were analyzed using chi(2) tests. RESULTS: We found a statistically significant
      improvement in the advisement of patients with psoriasis regarding their
      increased risk for cardiovascular disease, to contact their primary care provider
      for cardiovascular risk assessment, and in shared decision making regarding the
      treatment plan. We also found an overall statistically significant improvement in
      history taking per the guidelines. LIMITATIONS: Learner chart selection bias,
      self-reporting of chart data, and lack of a control group are limitations.
      CONCLUSIONS: The AAD psoriasis PI CME activity demonstrated significantly
      improved dermatologists' documentation of patient's history, counseling of
      patients for lifestyle behaviors, and shared decision making.

PMID- 25575688
TI  - Drug transporters play a key role in the complex process of Imatinib resistance
      in vitro.
AB  - Imatinib resistance has been associated with BCR-ABL alterations, but other
      mechanisms might be involved, like drug transporters. Additionally, the impact of
      poor adherence in resistance has been little explored. Using sensitive and
      resistance CML cell lines, we investigated the expression of influx/efflux
      transporters, like P-gP and OCT1. In the therapeutic interruption model, we
      observed decrease of influx and increase in efflux transporters combined with BCR
      ABL over-expression. Comparatively, resistant cells obtained by continuous TKI
      exposure only demonstrated alterations in drug's transporters. By exploring P-gP
      expression of resistant cells, we observed the potential of P-gP inhibitor in
      circumventing Imatinib resistance. Our results revealed the importance of
      treatment interruptions for expected response levels and show the complexity of
      Imatinib resistant process. Efflux transports appear as not only relevant for
      acquisition of resistant phenotype, but also as valid therapeutic tool for
      managing resistance. 

PMID- 25575689
TI  - Bioinformatic analysis of a PLP-dependent enzyme superfamily suitable for
      biocatalytic applications.
AB  - In this review we analyse structure/sequence-function relationships for the
      superfamily of PLP-dependent enzymes with special emphasis on class III
      transaminases. Amine transaminases are highly important for applications in
      biocatalysis in the synthesis of chiral amines. In addition, other enzyme
      activities such as racemases or decarboxylases are also discussed. The substrate
      scope and the ability to accept chemically different types of substrates are
      shown to be reflected in conserved patterns of amino acids around the active
      site. These findings are condensed in a sequence-function matrix, which
      facilitates annotation and identification of biocatalytically relevant enzymes
      and protein engineering thereof. 

PMID- 25575690
TI  - Radiation therapy and the global health agenda.

PMID- 25575691
TI  - Frequency of moderate-to-vigorous physical activity (MVPA) is a greater predictor
      of systemic inflammation than total weekly volume of MVPA: Implications for
      physical activity promotion.
AB  - Few studies have differentiated the effects of total physical activity volume vs.
      physical activity frequency on health. Therefore, the purpose of this study was
      to examine whether daily frequency of moderate-to-vigorous physical activity
      (MVPA) throughout the week or overall weekly accumulation of MVPA is a greater
      predictor of systemic inflammation. Data from the 2003-2006 NHANES were used,
      which included 2330 adults (>= 20 years). Participants wore an accelerometer for
      7 days to assess physical activity, with C-reactive protein (CRP) measured from a
      blood sample. Only participants with 7 valid (10+ hours/day of monitoring) days
      of monitoring were included. Two physical activity variables were created: 1)
      total weekly accumulation of MVPA, and 2) the number of days per week
      participants engaged in >= 30 min/day of MVPA. After adjusting for age, gender,
      race-ethnicity, poverty level, comorbid illness, body mass index, sedentary
      behavior, and smoking status, participants engaging in more days of >= 30 min/day
      of MVPA had lower log-transformed CRP levels (beta=-0.01, P<.001), and in a
      separate multivariate model, total weekly MVPA volume (beta=-0.005, P=.002) was
      also inversely associated with log-transformed CRP levels. However, when both
      MVPA frequency and total weekly volume were entered into the model at the same
      time, MVPA frequency remained significant (beta=-0.01, P=.04), but total weekly
      MVPA volume was no longer significant (beta=-0.001, P=.82). In conclusion, MVPA
      frequency, compared to total weekly MVPA accumulation, is a stronger predictor of
      CRP among the U.S. adults. Clinicians are encouraged to advise their patients to
      engage in consistent physical activity throughout the week.

PMID- 25575692
TI  - Can low-level ethanol exposure during pregnancy influence maternal care? An
      investigation using two strains of rat across two generations.
AB  - Gestational alcohol use is well documented as detrimental to both maternal and
      fetal health, producing an increase in offspring's tendency for alcoholism, as
      well as in behavioral and neuropsychological disorders. In both rodents and in
      humans, parental care can influence the development of offspring physiology and
      behavior. Animal studies that have investigated gestational alcohol use on
      parental care and/or their interaction mostly employ heavy alcohol use and single
      strains. This study aimed at investigating the effects of low gestational ethanol
      dose on parental behavior and its transgenerational transmission, with comparison
      between two rat strains. Pregnant Sprague Dawley (SD) and Long Evans (LE)
      progenitor dams (F0) received 1g/kg ethanol or water through gestational days 17
      20 via gavage, or remained untreated in their home cages. At maturity, F1 female
      offspring were mated with males of the same strain and treatment and were left
      undisturbed through gestation. Maternal behavior was scored in both generations
      during the first six postnatal days. Arch-back nursing (ABN) was categorized as:
      1, when the dam demonstrated minimal kyphosis; 2, when the dam demonstrated
      moderate kyphosis; and 3, when the dam displayed maximal kyphosis. Overall, SD
      showed greater amounts of ABN than LE dams and spent more time in contact with
      their pups. In the F0 generation, water and ethanol gavage increased ABN1 and
      contact with pups in SD, behaviors which decreased in treated LE. For ABN2,
      ethanol-treated SD dams showed more ABN2 than water-treated dams, with no effect
      of treatment on LE animals. In the F1 generation, prenatal exposure affected
      retrieval. Transgenerational transmission of LG was observed only in the
      untreated LE group. Strain-specific differences in maternal behavior were also
      observed. This study provides evidence that gestational gavage can influence
      maternal behavior in a strain-specific manner. Our results also suggest that the
      experimental procedure during gestation and genetic variations between strains
      may play an important role in the behavioral effects of prenatal manipulations. 

PMID- 25575693
TI  - Age-related changes of brain iron load changes in the frontal cortex in
      APPswe/PS1DeltaE9 transgenic mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating
      pathology leading to disastrous cognitive impairments and dementia, associated
      with major social and economic costs to society. Iron can catalyze damaging free
      radical reactions. With age, iron accumulates in brain frontal cortex regions and
      may contribute to the risk of AD. In this communication, we investigated the age
      related brain iron load changes in the frontal cortex of 6- and 12-month-old
      C57BL/6J (C57) and APPswe/PS1DeltaE9 (APP/PS1) double transgenic mouse by using
      graphite furnace atomic absorption spectrometry (GFAAS) and Perls' reaction. In
      the present study, we also evaluated the age-related changes of DMT1 and FPN1 by
      using Western blot and qPCR. We found that compared with 6-month-old APP/PS1 mice
      and the 12-month-old C57 mice, the 12-month-old APP/PS1 mice had increased iron
      load in the frontal cortex. The levels of DMT1 were significantly increased and
      the FPN1 were significantly reduced in the frontal cortex of the 12-month-old
      APP/PS1 mice than that in the 6-month-old APP/PS1 mice and 12-month-old C57 mice.
      We conclude that in AD damage occurs in conjunction with iron accumulation, and
      the brain iron load associated with loss control of the brain iron metabolism
      related protein DMT1 and FPN1 expressions. 

PMID- 25575694
TI  - Blood lead level and its relationship to essential elements in preschool children
      from Nanning, China.
AB  - OBJECTIVE: Our study aimed to assess the distribution of blood lead level and its
      relationship to essential elements in preschool children in an urban area of
      China. DESIGN AND METHODS: A total of 6741 children aged 0- to 6-year-old were
      recruited. Levels of lead, zinc, copper, iron, calcium, and magnesium in whole
      blood samples were determined using atomic absorption spectrometry. RESULTS: The
      mean blood lead level (BLL) and the prevalence of BLL>=10MUg/dl (5.26+/
      4.08MUg/dl and 6.84%, respectively) increased with age gradually, and there was a
      gender-difference for blood lead, copper, zinc and iron levels. Compared with the
      group of children who had BLLs<5MUg/dl, the groups of 5<=BLLs<10MUg/dl and
      10<=BLLs<15MUg/dl showed higher blood zinc, iron and magnesium levels, and a
      lower blood calcium level. A positive correlation of lead with zinc, iron and
      magnesium, and a negative correlation of lead with calcium were found in the
      group of children with BLL<5MUg/dl. CONCLUSION: Age- and gender-differences were
      found when assessing the BLL and intoxication prevalence in preschool children.
      Metabolic disorder of essential elements was found even with a low level of lead
      exposure.

PMID- 25575695
TI  - Postnatal interleukin-1beta administration after experimental prolonged febrile
      seizures enhances epileptogenesis in adulthood.
AB  - It remains unclear whether prolonged febrile seizures (pFS) in childhood
      facilitate mesial temporal lobe epilepsy (MTLE) in adulthood. Interleukin (IL)
      1beta is associated with seizures in children and immature animal models. Here,
      we use a rat model of pFS to study the effects of IL-1beta on adult
      epileptogenesis, hippocampal damage, and cognition. We produced prolonged
      hyperthermia-induced seizures on postnatal days (P) 10-11 and administered IL
      1beta or saline intranasally immediately after the seizures. Motor and cognitive
      functions were assessed at P85 using rotarod and passive avoidance tests.
      Electroencephalogram recordings were conducted at P90 and P120. Hippocampal CA1
      and CA3 neurons and gliosis were quantified at the end of the experiment.
      Spontaneous seizure incidence was significantly greater in rats that had received
      IL-1beta than in those that had received saline or those without hyperthermia
      induced seizures (p < 0.05). Seizure frequency did not differ significantly
      between the three groups and no motor deficits were observed. Passive avoidance
      learning was impaired in rats that received IL-1beta compared with controls (p <
      0.05), but was not different from that in rats that received saline. Hippocampal
      cell numbers and gliosis did not differ between the three groups. These results
      indicate that neuronal loss and gliosis are not prerequisites for the
      epileptogenic process that follows pFS. Our results suggest that infantile pFS
      combined with IL-1beta overproduction can enhance adulthood epileptogenesis, and
      might contribute to the development of MTLE. 

PMID- 25575696
TI  - The role of IL-21 in immunity and cancer.
AB  - Interleukin-21 (IL-21), produced predominantly by CD4+ T cells and natural killer
      T (NKT) cells, is a newly discovered member of the common gamma-chain family of
      cytokines. It has been implicated in many immunological processes and has been
      linked to autoimmune diseases, allergies and other inflammatory diseases. In
      recent years, the role for IL-21 in the pathogenesis of cancer has also been
      extensively studied. In this review, we will discuss recent advances concerning
      the role of IL-21 in immunological processes and the pathogenesis of cancer. 

PMID- 25575697
TI  - The acute effects of tobacco smoking and alcohol consumption on video-lottery
      terminal gambling.
AB  - RATIONALE: Gamblers often use alcohol and/or tobacco when they gamble but little
      is known about the extent to which drinking or smoking affects gambling behavior.
      OBJECTIVES: This study examined the acute effects of alcohol and nicotine
      containing tobacco administration on the subjective and behavioral responses to
      video-lottery terminal (VLT) gambling in 16 regular video-lottery terminal
      players (11 male) who were also regular consumers of alcohol and tobacco.
      METHODS: During four double-blind, counterbalanced sessions, participants
      assessed the subjective effects of nicotine-containing tobacco or denicotinized
      tobacco following the administration of a moderately intoxicating dose of alcohol
      or a placebo beverage. They were then given $40 and provided with an opportunity
      to gamble using an authentic VLT. RESULTS: Alcohol administration was associated
      with increased ratings of several subjective descriptors including "intoxicated",
      "high", "want alcohol", "crave cigarette", and "want to gamble" but did not
      affect subsequent gambling behavior. In contrast, relative to denicotinized
      tobacco, the administration of nicotine containing tobacco was associated with
      increased average wagers, but did not significantly alter subjective state.
      CONCLUSIONS: Findings suggest that both alcohol and nicotine-containing tobacco
      may acutely increase the propensity to gamble using VLTs, but they may do so
      through separate processes.

PMID- 25575698
TI  - Procalcitonin in the assessment of bacteraemia in emergency department patients:
      results of a large retrospective study.
AB  - BACKGROUND: The aim of this study was to evaluate the use of procalcitonin in the
      assessment of bacteraemia in patients in the emergency department, both alone and
      in conjunction with existing inflammatory markers of bacterial infection.
      METHODS: We enrolled 3305 cases (range 20-90 years) for which we retrospectively
      compared procalcitonin concentration, blood culture results, body temperature,
      absolute neutrophil count, and C-reactive protein concentration. The positive
      predictive value and the negative predictive value of procalcitonin were
      established at different cut-off concentrations. Receiver operating
      characteristic curves were plotted, and the areas under the ROC curves
      calculated, to allow assessment of the diagnostic accuracy of (a) a combination
      of three existing inflammatory markers of bacterial infection (body temperature,
      C-reactive protein, absolute neutrophil count), and (b) this combination with
      procalcitonin. RESULTS: Positive predictive values of procalcitonin using 0.1, 1,
      2, and 5 ng/mL as the cut-off values were 21.2, 32.2, 34.2, and 37.0%,
      respectively. Negative predictive values of procalcitonin using 0.1, 1, 2, and 5
      ng/mL as the cut-off values were 95.1, 92.2, 91.1, and 89.0%, respectively. Areas
      under the curve of three inflammatory markers (absolute neutrophil count, C
      reactive protein, and body temperature) combined was 0.879; areas under the curve
      of these markers combined with procalcitonin was 0.932 (p = 0.018). CONCLUSIONS:
      When procalcitonin is used as a serum marker for ruling out bacteraemia, a cut
      off of 0.1 ng/mL may be used. Procalcitonin improves the diagnostic accuracy of
      existing markers of bacteraemia.

PMID- 25575699
TI  - Appropriateness of prescribing thyroxine in primary care.
AB  - INTRODUCTION: A practice hypothyroid register is part of the quality and outcomes
      framework. In literature, the prevalence of hypothyroidism is stated to be 2% but
      the prevalence, defined from quality and outcomes framework data, is 3.2% in the
      UK and 3.6% in Plymouth. We sought to investigate the diagnosis of hypothyroidism
      and reasons for prescription of thyroxine to patients on the hypothyroid register
      in Plymouth. METHODS: A letter was sent to the 10 practices with the highest
      prevalence of hypothyroidism requesting a list of patients on their registers.
      The hospital pathology system was used to identify those with biochemically
      documented hypothyroidism (defined as thyroid stimulating hormone >10 mU/L) For
      two large practices the clinical records of the remaining patients were reviewed
      to ascertain the reasons for prescription of thyroxine and whether it led to
      symptomatic improvement. RESULTS: Seven practices responded with 1246 patients on
      their registers, of whom 43.6% had documented hypothyroidism. A review of notes
      of patients on the register, but without documented hypothyroidism, showed <25%
      to have an improvement in symptoms after prescription of thyroxine. Tiredness was
      the most common symptom prompting prescription of thyroxine. CONCLUSION: Of the
      patients on the register, only 43.6% had documented biochemical evidence of
      hypothyroidism and, from notes review of those without documented hypothyroidism,
      at least two-thirds may have been prescribed thyroxine outwith current national
      guidance. If this is correct, it has significant resource implications, impacts
      upon the workload of primary care, pharmacy and the laboratory service and may
      have clinical implications for patients.

PMID- 25575700
TI  - Focused metabolomics using liquid chromatography/electrospray ionization tandem
      mass spectrometry for analysis of urinary conjugated cholesterol metabolites from
      patients with Niemann-Pick disease type C and 3beta-hydroxysteroid dehydrogenase
      deficiency.
AB  - BACKGROUND: Various conjugated cholesterol metabolites are excreted in urine of
      the patients with metabolic abnormalities and hepatobiliary diseases. We aimed to
      examine the usefulness of precursor ion scan and neutral loss scan for the
      characterization of conjugated cholesterol metabolites in urine. METHODS: A
      mixture of authentic standards of conjugated cholesterol metabolites was used for
      investigating the performance of the present method. The urine of patients with
      Niemann-Pick diseases type C and 3beta-hydroxysteroid dehydrogenase deficiency
      were analysed by precursor ion scan of m/z 97, 74, and 124. RESULTS: A precursor
      ion scan of m/z 97 was effective for identifying conjugates with ester sulphates
      on hydroxyl groups whereas ester sulphates on phenolic alcohols were signalled by
      a neutral loss scan of 80 Da. Monosaccharide-conjugated cholesterol metabolites
      were signalled by a precursor ion scan of m/z 113. Although precursor ion scan of
      m/z 74 and 124 was effective for finding glycine- and taurine-conjugated
      metabolites, high intensity of product ions (m/z 74 and 124) disturbed
      measurement of other multiply conjugated metabolites. The urine samples contained
      many conjugated cholesterol metabolites, and there were several disease-specific
      intense peaks. We found several unknown intense peaks with three known peaks in
      urine of the Niemann-Pick type C patient. In the patient with 3beta
      hydroxysteroid dehydrogenase deficiency, intense peaks that were tentatively
      identified as 5-cholenoic acid sulphates and their glycine and taurine conjugates
      were present. CONCLUSION: The method should lead to the discovery of new urinary
      biomarkers for these disturbances of cholesterol catabolism and transport.

PMID- 25575701
TI  - Application of WHO recommendations in outcome assessment of clinical series
      published in hand surgery journals with five years interval.
AB  - Outcome measurement is becoming increasingly important in hand surgery. The
      International classification of functioning, disability and health (ICF), is a
      WHO multi-dimensional approach to health condition including three domains: body
      "functions and structures", activities and participation. The aim of this study
      was to measure how often these three ICF domains were included in outcome
      measurements of the clinical series published in the American, European and
      French hand surgery journals. Our study included clinical series published in
      2007 and 2012 in the American Journal Of Hand Surgery, European Journal Of Hand
      Surgery and Chirurgie de la Main. Analysis of each of these publications was done
      in two steps. First, we checked the presence or absence of the three domains of
      ICF in outcome measurement without considering the way it was measured. Then, we
      reported the use of evaluation instruments and/or quantitative measurement for
      each domain. We included 54 series in 2007 and 119 in 2012. The number of series
      reporting on the three domains and using at least one quantitative measurement
      for each domain represents 6% of articles in 2007 and 10% in 2012. This study
      shows that the quality of outcome measurement has improved over these 5 years,
      but remains poor according to the ICF recommendation.

PMID- 25575702
TI  - Filling in the gaps of the papilionoid legume phylogeny: the enigmatic Amazonian
      genus Petaladenium is a new branch of the early-diverging Amburaneae clade.
AB  - Recent deep-level phylogenies of the basal papilionoid legumes (Leguminosae,
      Papilionoideae) have resolved many clades, yet left the phylogenetic placement of
      several genera unassessed. The phylogenetically enigmatic Amazonian monospecific
      genus Petaladenium had been believed to be close to the genera of the Genistoid
      Ormosieae clade. In this paper we provide the first DNA phylogenetic study of
      Petaladenium and show it is not part of the large Genistoid clade, but is a new
      branch of the Amburaneae clade, one of the first-diverging lineages of the
      Papilionoideae phylogeny. This result is supported by the chemical observation
      that the quinolizidine alkaloids, a chemical synapomorphy of the Genistoids, are
      absent in Petaladenium. Parsimony and Bayesian phylogenetic analysis of nuclear
      ITS/5.8S and plastid matK and trnL intron agree with a new interpretation of
      morphology that Petaladenium is sister to Dussia, a genus comprising ~18 species
      of trees largely confined to rainforests in Central America and northern South
      America. Petaladenium, Dussia, and Myrospermum have papilionate flowers in a
      clade otherwise with radial floral symmetry, loss of petals or incompletely
      differentiated petals. Our phylogenetic analyses also revealed well-supported
      resolution within the three main lineages of the ADA clade (Angylocalyceae,
      Dipterygeae, and Amburaneae). We also discuss further molecular phylogenetic
      evidence for the undersampled Amazonian genera Aldina and Monopteryx, and the
      tropical African Amphimas, Cordyla, Leucomphalos, and Mildbraediodendron. 

PMID- 25575703
TI  - Transfusion-related acute lung injury following coronary artery bypass graft
      surgery.
AB  - Blood transfusion is sometimes a necessary procedure during or following coronary
      artery bypass graft (CABG) surgery. However, transfusion-related acute lung
      injury (TRALI)/possible TRALI is a rare and fatal complication and characterized
      by acute hypoxemia and non-cardiogenic pulmonary edema that occurs within 6 hours
      following a transfusion. Anti-leukocyte antibodies or, possibly, other bioactive
      substances cause inflammation and capillary endothelial destruction in
      susceptible recipients' lungs. Prompt diagnosis and mechanical ventilatory
      support are important. A successful treatment of two male patients following CABG
      surgery, compatible with TRALI/possible TRALI, is presented here. 

PMID- 25575704
TI  - Dramatic regression of coronary artery stenosis three years after diagnosis.
AB  - While strategies for the prevention of the progression of coronary artery lesions
      have been proposed, documentation of the regression of significant coronary
      artery lesions is rare. Lifestyle modifications and exercise have been reported
      to influence the regression of coronary disease, but a dramatic disappearance of
      coronary artery lesions demonstrated angiographically has been rarely reported.
      We describe a case where diet and lifestyle modifications, along with lipid
      lowering therapy, led to the significant regression of coronary artery stenosis. 

PMID- 25575705
TI  - A paediatric ECMO case of plasma leakage through a polymethylpentene oxygenator.
AB  - Polymethylpentene (PMP) oxygenators, utilised for ECMO, are commonly believed to
      be resistant to plasma leakage. Whilst uncommon, plasma leakage has been
      previously reported with PMP fibres, both in vivo and in vitro. We describe a
      paediatric ECMO case during which plasma leakage occurred and oxygenator function
      gradually deteriorated, ultimately necessitating device replacement. To our
      knowledge, this is the first case of plasma leakage described using a PMP device
      during paediatric ECMO. Subsequent investigation is described, demonstrating that
      a protein coating reduces the free passage of solution across the PMP membrane. 

PMID- 25575706
TI  - The ORF3 protein of porcine circovirus type 2 promotes secretion of IL-6 and IL-8
      in porcine epithelial cells by facilitating proteasomal degradation of regulator
      of G protein signalling 16 through physical interaction.
AB  - Porcine circovirus type 2 (PCV2) is the main aetiological agent of postweaning
      multisystemic wasting syndrome. The mechanism of pathogenicity associated with
      PCV2 infection is still not fully understood. Nevertheless, the fact that large
      amounts of proinflammatory cytokines within lymphoid tissues are released during
      the early stage of PCV2 infection may induce chronic inflammatory responses
      followed by the destruction of lymphoid tissues. However, how PCV2 infection
      causes an excessive inflammatory response in the host immune system during the
      early stage of PCV2 infection has still not been elucidated. In this study, we
      show that direct interaction between the PCV2 ORF3 and regulator of G protein
      signalling 16 (RGS16) within the cytoplasm of host cells leads to ubiquitin
      mediated proteasomal degradation of RGS16. Facilitated degradation of the RGS16
      by PCV2 ORF3 further enhances NFkappaB translocation into the nucleus through the
      ERK1/2 signalling pathway and increased IL-6 and IL-8 mRNA transcripts.
      Consequently, more severe inflammatory responses and leukocyte infiltration occur
      around host cells. This evidence may be the first clue explaining the molecular
      basis of how excessive amounts of proinflammatory cytokines within lymphoid
      tissues are released during the early stage of PCV2 infection.

PMID- 25575707
TI  - Murine cytomegalovirus strains co-replicate at multiple tissue sites and
      establish co-persistence in salivary glands in the absence of Ly49H-mediated
      competition.
AB  - Infection with multiple genetically distinct strains of pathogen is common and
      can lead to positive (complementation) or negative (competitive) within-host
      interactions. These interactions can alter aspects of the disease process and
      help shape pathogen evolution. Infection of the host with multiple strains of
      cytomegalovirus (CMV) occurs frequently in humans and mice. Profound, NK-cell
      mediated (apparent) competition has been identified in C57BL/6 mice, and
      prevented the replication and shedding of certain co-infecting CMV strains.
      However, the frequency of such strong competition has not been established. Other
      within-host interactions such as complementation or alternative forms of
      competition remain possible. Moreover, high rates of recombination in both human
      CMV and murine CMV (MCMV) suggest prolonged periods of viral co-replication,
      rather than strong competitive suppression. An established model was employed to
      investigate the different possible outcomes of multi-strain infection in other
      mouse strains. In this study, co-replication of up to four strains of MCMV in the
      spleen, liver and salivary glands was observed in both MCMV-susceptible and MCMV
      resistant mice. In the absence of apparent competition, no other forms of
      competition were unmasked. In addition, no evidence of complementation between
      viral strains was observed. Importantly, co-replication of MCMV strains was
      apparent for up to 90 days in the salivary glands. These data indicated that
      competition was not the default outcome of multi-strain CMV infection. Prolonged,
      essentially neutral, co-replication may be the norm, allowing for multi-strain
      transmission and prolonged opportunities for recombination.

PMID- 25575708
TI  - Genetic interaction between NS4A and NS4B for replication of Japanese
      encephalitis virus.
AB  - Flavivirus NS4A and NS4B are important membrane proteins for viral replication
      that are assumed to serve as the scaffold for the formation of replication
      complexes. We previously demonstrated that a single Lys-to-Arg mutation at
      position 79 in NS4A (NS4A-K79R) significantly impaired Japanese encephalitis
      virus (JEV) replication. In this study, the mutant virus was subject to genetic
      selection to search for the potential interaction between NS4A and other viral
      components. Sequencing of the recovered viruses revealed that, in addition to an
      A97E change in NS4A itself, a Y3N compensatory mutation located in NS4B had
      emerged from independent selections. Mutagenesis analysis, using a genome-length
      RNA and a replicon of JEV, demonstrated that both adaptive mutations greatly
      restored the replication defect caused by NS4A-K79R. Our results, for the first
      time to our knowledge, clearly showed the genetic interaction between NS4A and
      NS4B, although the mechanism underlying their interaction is unknown. 

PMID- 25575709
TI  - Informed drug choices for neuropathic pain.

PMID- 25575710
TI  - Pharmacotherapy for neuropathic pain in adults: a systematic review and meta
      analysis.
AB  - BACKGROUND: New drug treatments, clinical trials, and standards of quality for
      assessment of evidence justify an update of evidence-based recommendations for
      the pharmacological treatment of neuropathic pain. Using the Grading of
      Recommendations Assessment, Development, and Evaluation (GRADE), we revised the
      Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the
      pharmacotherapy of neuropathic pain based on the results of a systematic review
      and meta-analysis. METHODS: Between April, 2013, and January, 2014, NeuPSIG of
      the International Association for the Study of Pain did a systematic review and
      meta-analysis of randomised, double-blind studies of oral and topical
      pharmacotherapy for neuropathic pain, including studies published in peer
      reviewed journals since January, 1966, and unpublished trials retrieved from
      ClinicalTrials.gov and websites of pharmaceutical companies. We used number
      needed to treat (NNT) for 50% pain relief as a primary measure and assessed
      publication bias; NNT was calculated with the fixed-effects Mantel-Haenszel
      method. FINDINGS: 229 studies were included in the meta-analysis. Analysis of
      publication bias suggested a 10% overstatement of treatment effects. Studies
      published in peer-reviewed journals reported greater effects than did unpublished
      studies (r(2) 9.3%, p=0.009). Trial outcomes were generally modest: in
      particular, combined NNTs were 6.4 (95% CI 5.2-8.4) for serotonin-noradrenaline
      reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7.7 (6.5
      9.4) for pregabalin; 7.2 (5.9-9.21) for gabapentin, including gabapentin extended
      release and enacarbil; and 10.6 (7.4-19.0) for capsaicin high-concentration
      patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol,
      and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE,
      final quality of evidence was moderate or high for all treatments apart from
      lidocaine patches; tolerability and safety, and values and preferences were
      higher for topical drugs; and cost was lower for tricyclic antidepressants and
      tramadol. These findings permitted a strong recommendation for use and proposal
      as first-line treatment in neuropathic pain for tricyclic antidepressants,
      serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak
      recommendation for use and proposal as second line for lidocaine patches,
      capsaicin high-concentration patches, and tramadol; and a weak recommendation for
      use and proposal as third line for strong opioids and botulinum toxin A. Topical
      agents and botulinum toxin A are recommended for peripheral neuropathic pain
      only. INTERPRETATION: Our results support a revision of the NeuPSIG
      recommendations for the pharmacotherapy of neuropathic pain. Inadequate response
      to drug treatments constitutes a substantial unmet need in patients with
      neuropathic pain. Modest efficacy, large placebo responses, heterogeneous
      diagnostic criteria, and poor phenotypic profiling probably account for moderate
      trial outcomes and should be taken into account in future studies. FUNDING:
      NeuPSIG of the International Association for the Study of Pain.

PMID- 25575712
TI  - An editor's considerations in publishing industry-sponsored studies.
AB  - The fundamental responsibility of a journal editor is to assure that studies
      accepted for publication provide rigorous original scientific information and
      reviews that are considered important to the readership. The fundamental
      requirements of such reports from an editor's perspective include objectivity and
      transparency in each of the study design, implementation of investigation
      methods, acquisition of data, inclusive analysis and interpretation of results,
      appropriate application of statistical methods, presentation of outcomes in the
      context of a balanced and comprehensive review of relevant literature, and
      meaningful conclusions. In proceeding on these presumptions, editors then have
      the responsibility of obtaining rigorous, objective, and constructive reviews of
      these reports so that they can make an unbiased decision regarding their
      disposition. The fundamental objective in this is to enhance the ultimate
      scientific validity and value of the work if and when it is accepted for
      publication. Guidelines have been advanced by several organizations to identify
      how such editorial responsibilities can be fulfilled. These guidelines also
      pertain to investigators, authors, and sponsors of the studies, which the various
      reports and reviews describe. The present article reviews these guidelines as
      they relate to both industry-sponsored and investigator-initiated investigations
      and as relevant to the variety of reports that a scientific/medical journal such
      as Urologic Oncology: Seminars and Original Investigations receives for
      publication.

PMID- 25575711
TI  - High expression of long intervening non-coding RNA OLMALINC in the human cortical
      white matter is associated with regulation of oligodendrocyte maturation.
AB  - BACKGROUND: Long intervening non-coding RNAs (lincRNAs) are a recently discovered
      subclass of non-coding RNAs. LincRNAs are expressed across the mammalian genome
      and contribute to the pervasive transcription phenomenon. They display a tissue
      specific and species-specific mode of expression and are present abundantly in
      the brain. RESULTS: Here, we report the expression patterns of oligodendrocyte
      maturation-associated long intervening non-coding RNA (OLMALINC), which is highly
      expressed in the white matter (WM) of the human frontal cortex compared to the
      grey matter (GM) and peripheral tissues. Moreover, we identified a novel isoform
      of OLMALINC that was also up-regulated in the WM. RNA-interference (RNAi)
      knockdown of OLMALINC in oligodendrocytes, which are the major cell type in the
      WM, caused significant changes in the expression of genes regulating
      cytostructure, cell activation and membrane signaling. Gene ontology enrichment
      analysis revealed that over 10% of the top 25 up- and down-regulated genes were
      involved in oligodendrocyte maturation. RNAi experiments in neuronal cells
      resulted in the perturbation of genes controlling cell proliferation.
      Furthermore, we identified a novel cis-natural antisense non-coding RNA, which we
      named OLMALINC-AS, which maps to the first exon of the dominant isoform of
      OLMALINC. CONCLUSIONS: Our study has demonstrated for the first time that a
      primate-specific lincRNA regulates the expression of genes critical to human
      oligodendrocyte maturation, which in turn might be regulated by an antisense
      counterpart.

PMID- 25575713
TI  - Urokinase-type plasminogen activator receptor (uPAR) expression is associated
      with T-stage and survival in urothelial carcinoma of the bladder.
AB  - OBJECTIVES: To evaluate the expression-and localization pattern of the urokinase
      type plasminogen activator receptor (uPAR), focusing on its clinical implications
      in patients with urothelial neoplasia of the bladder treated with radical
      cystectomy. uPAR is a central molecule in tissue remodeling during cancer
      invasion and metastasis and is an established prognostic marker in cancer. The
      expression and localization of uPAR and its prognostic significance is only
      limitedly investigated in urothelial bladder neoplasia. MATERIALS AND METHODS:
      The expression-and localization pattern of uPAR was investigated in formalin
      fixed paraffin-embedded tumor tissue from 149 patients treated with radical
      cystectomy between 1988 and 2005. uPAR expression was determined by
      immunohistochemistry and scored as either negative or positive. Separate values
      were obtained for cancer cells, macrophages, and myofibroblasts at the invasive
      front and tumor core, respectively. Statistical analyses were performed to
      evaluate the association of uPAR localization and score with clinicopathologic
      covariates and survival. RESULTS: uPAR positivity was seen in 122/137 (89%) and
      118/149 (74%) of the neoplasias at the invasive front and tumor core,
      respectively. uPAR was primarily expressed by myofibroblasts and macrophages in
      the surrounding stroma as well as some cancer cells. A significant association
      between uPAR positivity and T-stage as well as grade was found for all 3 cell
      types in tumor core (P <= 0.04 for all comparisons). In univariate analysis, the
      uPAR positive group had a shorter survival than the uPAR negative group (hazard
      ratio = 2.39; 95% CI: 1.15-5.01; P = 0.020). CONCLUSIONS: The expression of uPAR
      is a possible prognostic marker that could be useful in identification of
      patients with aggressive, highly invasive tumors that could benefit from
      additional chemotherapy or more intensive follow-up after cystectomy.

PMID- 25575714
TI  - Immunotherapy for castration-resistant prostate cancer: Progress and new
      paradigms.
AB  - BACKGROUND: The approval of sipuleucel-T in conjunction with data from other
      immunotherapeutic trials for prostate cancer and other solid tumors demonstrates
      the potential of harnessing the patients' immune system for long-term survival.
      Thus, a range of therapeutic approaches are under evaluation. This review
      describes the rationale for immunotherapy for prostate cancer, summarizes the
      approaches under evaluation, and discusses sequencing options for immunotherapy
      in the current treatment paradigm. DESIGN: References for this review were
      identified through searches of PubMed with the search terms "prostate cancer,"
      "immune system," "vaccine," "immunotherapy," and "T cells." Articles were also
      identified through searches of the authors' own files. The final reference list
      was generated based on originality and relevance. RESULTS: The immune system can
      recognize and respond to prostate tumor antigens, effected through tumor
      associated antigens and tumor infiltration of immune effector cells. However,
      evidence also suggests that prostate tumors are adept at escaping immunological
      recognition, thus hypothesizing multiple therapeutic strategies. Therapeutic
      approaches could include vaccination and modulation of T-cell function via the
      blockade of checkpoint receptors such as cytotoxic T-lymphocyte antigen-4 and
      programmed death 1. In phase III trials, sipuleucel-T improved overall survival
      for an M1 patient population with castration-resistant prostate cancer and
      ipilimumab also did so when given after radiotherapy in a subset of better risk
      patients. In randomized phase II trials, prostate-specific antigen-TRICOM
      improved overall survival and tasquinimod improved progression-free survival.
      CONCLUSION: Although immunotherapy has the potential to affect advanced prostate
      cancer, additional research is needed to (1) identify predictive or surrogate
      markers of activity, (2) understand which agents are clinically effective alone
      or in combination with other therapies, and (3) define the optimal timing for an
      immunotherapy to achieve maximal benefit.

PMID- 25575715
TI  - Prognostic accuracy of Prostate Health Index and urinary Prostate Cancer Antigen
      3 in predicting pathologic features after radical prostatectomy.
AB  - OBJECTIVE: To compare the prognostic accuracy of Prostate Health Index (PHI) and
      Prostate Cancer Antigen 3 in predicting pathologic features in a cohort of
      patients who underwent radical prostatectomy (RP) for prostate cancer (PCa).
      METHODS AND MATERIALS: We evaluated 156 patients with biopsy-proven, clinically
      localized PCa who underwent RP between January 2013 and December 2013 at 2
      tertiary care institutions. Blood and urinary specimens were collected before
      initial prostate biopsy for [-2] pro-prostate-specific antigen (PSA), its
      derivates, and PCA3 measurements. Univariate and multivariate logistic regression
      analyses were carried out to determine the variables that were potentially
      predictive of tumor volume > 0.5 ml, pathologic Gleason sum >= 7, pathologically
      confirmed significant PCa, extracapsular extension, and seminal vesicles
      invasions. RESULTS: On multivariate analyses and after bootstrapping with 1,000
      resampled data, the inclusion of PHI significantly increased the accuracy of a
      baseline multivariate model, which included patient age, total PSA, free PSA,
      rate of positive cores, clinical stage, prostate volume, body mass index, and
      biopsy Gleason score (GS), in predicting the study outcomes. Particularly, to
      predict tumor volume > 0.5, the addition of PHI to the baseline model
      significantly increased predictive accuracy by 7.9% (area under the receiver
      operating characteristics curve [AUC] = 89.3 vs. 97.2, P>0.05), whereas PCA3 did
      not lead to a significant increase. Although both PHI and PCA3 significantly
      improved predictive accuracy to predict extracapsular extension compared with the
      baseline model, achieving independent predictor status (all P's < 0.01), only PHI
      led to a significant improvement in the prediction of seminal vesicles invasions
      (AUC = 92.2, P < 0.05 with a gain of 3.6%). In the subset of patients with GS <=
      6, PHI significantly improved predictive accuracy by 7.6% compared with the
      baseline model (AUC = 89.7 vs. 97.3) to predict pathologically confirmed
      significant PCa and by 5.9% compared with the baseline model (AUC = 83.1 vs.
      89.0) to predict pathologic GS >= 7. For these outcomes, PCA3 did not add
      incremental predictive value. CONCLUSIONS: In a cohort of patients who underwent
      RP, PHI is significantly better than PCA3 in the ability to predict the presence
      of both more aggressive and extended PCa.

PMID- 25575716
TI  - [Comparison of GlideScope(r) Cobalt and McGrath(r) Series 5 video laryngoscopes
      with direct laryngoscopy in a simulated regurgitation/aspiration scenario].
AB  - BACKGROUND: Video laryngoscopy has become increasingly important in airway
      management in the pre- and intrahospital settings. However, using video
      laryngoscopes in the presence of body fluids can make visualization of the airway
      difficult. A simulated regurgitation model was used to compare two video
      laryngoscopes (VL) with direct laryngoscopy. MATERIALS AND METHODS: A total of 72
      physicians participated in this randomized trial. The hypopharynx from an Airway
      Management Trainer was filled with artificially warmed turbid liquid. In
      addition, the cervical spine of the manikin was immobilized. The VL GlideScope(r)
      (GS) and McGrath(r) Series 5 (McG) were examined with the laryngoscope with
      Macintoshspatel (DL). Fogging of the camera optics in percent (0 %= clear view,
      100 %= no view), the visibility of the glottis by Cormack and Lehane
      classification (C&L), and the POGO Score (percentage of glottic opening), the
      time until the endotracheal tube placement, and the success rate were evaluated.
      RESULTS: No fogging (median 0 %) was present using the GS (interquartile range
      [IQR]: 0-4), in contrast 45 % fogging was found in the McG group (IQR: 30-60; p <
      0.001). Glottic visualization using C&L was better using VL (p < 0.001). A
      similar result was observed using the POGO Scale: GS 90 % (IQR: 76-100), McG 80 %
      (IQR: 70-90), and DL 20 % (IQR: 0-50). The time for correct placement was in the
      DL with 27.6 s (IQR: 22.5-35) faster (p < 0.001), with the GS 48.5 s (IQR: 34.3
      65.1) and the McG 66.3 s (IQR: 45.4-90). Successful placement was possible with
      GS in all cases (72/72), with DL in 71/72 cases, and with the McG in 70/72 cases.
      CONCLUSION: Using a video laryngsocope with an "anti-fogging" system improved
      visualization in a simulated aspiration model. In this scenario, VL showed no
      advantage to direct laryngoscopy in terms of success rate and speed of
      intubation.

PMID- 25575717
TI  - Role of indirect readout mechanism in TATA box binding protein-DNA interaction.
AB  - Gene expression generally initiates from recognition of TATA-box binding protein
      (TBP) to the minor groove of DNA of TATA box sequence where the DNA structure is
      significantly different from B-DNA. We have carried out molecular dynamics
      simulation studies of TBP-DNA system to understand how the DNA structure alters
      for efficient binding. We observed rigid nature of the protein while the DNA of
      TATA box sequence has an inherent flexibility in terms of bending and minor
      groove widening. The bending analysis of the free DNA and the TBP bound DNA
      systems indicate presence of some similar structures. Principal coordinate
      ordination analysis also indicates some structural features of the protein bound
      and free DNA are similar. Thus we suggest that the DNA of TATA box sequence
      regularly oscillates between several alternate structures and the one suitable
      for TBP binding is induced further by the protein for proper complex formation. 

PMID- 25575718
TI  - Outcome 5 years after surgical treatment of acetabular fractures: a prospective
      clinical and radiographic follow-up of 101 patients.
AB  - INTRODUCTION: The aim of this study was to evaluate functional outcome after
      surgically treated acetabular fracture using radiography and patient-reported
      outcome measures, and to determine predictors of hip joint failure 5 years post
      surgery. PATIENTS AND METHODS: All patients with acetabular fractures treated
      with open reduction and internal fixation (ORIF) at our unit are prospectively
      entered into a local register. 101 acetabular fractures in 112 patients treated
      from 2004 to 2007 were eligible for analysis 5 years after surgery. Radiographs
      and questionnaires regarding physical function (Short Form[SF]-36) and pelvic
      discomfort index (PDI, 100 % = worst outcome) were obtained. The primary outcome
      measure was "joint failure" defined as either secondary total hip arthroplasty
      (THA) or a Girdlestone situation. Univariable analysis was used to compare
      patients with joint failure to those without, and binary logistic regression
      analysis was performed to identify risk factors of joint failure. RESULTS: 77 %
      of 101 followed patients had a preserved hip joint 5 years after surgery, and
      failure of the hip joint most often occurred within the first 2 years after
      injury. Patients with preserved hip joints had higher scores in the SF-36
      physical function domain (median 75 vs. 48; p = 0.004) and better PDI (28 vs. 43
      %, p = 0.03). Femoral head impaction was associated with an increased risk of
      joint failure [relative risk (RR) = 15.2, 95 % CI 3-95; p = 0.002], as was an age
      of >=60 years at the time of injury (RR = 4.2, CI 1.3-15; p = 0.02). CONCLUSIONS:
      Patients with failed hip joints after surgery for acetabular fracture have
      inferior global and disease-specific functional outcomes, even after secondary
      arthroplasty surgery. We suggest that patients with predictors of joint failure
      could benefit from other treatment strategies than ORIF, and primary insertion of
      THA may be an alternative treatment strategy for this subgroup.

PMID- 25575719
TI  - A special instrument to accurately and safely remove the femoral head.
AB  - BACKGROUND: Intracapsular hip fractures occur frequently, and most of them need
      operation. But current femoral head removal instruments used in the operation
      have many disadvantages. We optimized them. METHODS: We added a sleeve to the
      cork screw to strengthen the torque created by it. A scale is also added to the
      joint of the sleeve and the cork screw, which can be used to measure the depth of
      insertion. DISCUSSION: The optimized instrument decreased the risk and saved the
      time of operation.

PMID- 25575721
TI  - Study supports link between injectable hormonal contraceptive and HIV risk.

PMID- 25575720
TI  - Update TFCC: histology and pathology, classification, examination and
      diagnostics.
AB  - The TFCC is a crucial stabilizer of the DRUJ. Based on its superficial and deep
      fibers, the TFCC guarantees unrestricted pronation and supination which is
      essential for performing sophisticated tasks. The ability to perform complex
      movements is of uppermost importance for hand function. Therefore, a functional
      intact TFCC is a prerequisite in this context. The articular disc of the TFCC is
      a fibrocartilaginous extension of the superficial zone of hyaline articular
      cartilage which arises from the radius. The peripheral 10-40 % of the TFC is
      vascularized. Degeneration of the articular disc is common with increasing age.
      Even though the central part of the articular disc is avascular, potential
      regeneration of lesions could be detected. The Palmer and Atzei classifications
      of TFCC lesions are complementary. TFCC innervation is based on different nerves.
      There is a high variability. A diligent clinical examination facilitates specific
      tests which help to allocate symptoms to the pathology. Therefore, a thorough
      clinical examination is not dispensable. Wrist arthroscopy remains the "gold
      standard" for diagnosing TFCC pathologies despite technical progress in imaging
      modalities. MR arthrography may have the potential to become a real alternative
      to wrist arthroscopy for diagnosing TFCC pathologies with technical progress in
      the future. 

PMID- 25575722
TI  - [Modern diagnostics of cystic liver lesions and hemangiomas].
AB  - CLINICAL ISSUE: Cystic liver lesions incorporate a broad heterogeneous group of
      mostly benign but also malignant abnormalities. The radiological aim is the non
      invasive diagnosis with the use of different imaging modalities to determine the
      type of lesion. STANDARD RADIOLOGICAL METHODS: The common generally asymptomatic
      incidental findings of cystic lesions on ultrasound, computed tomography (CT) and
      magnetic resonance imaging (MRI) must be classified on the basis of specific
      imaging features. Such a differentiation is essential because the clinical
      consequences and the appropriate therapy can vary depending on the underlying
      pathology. Due to the morphological overlap of many cystic lesions, conventional
      radiological methods are often insufficient. METHODICAL INNOVATIONS: The huge
      advances in cross-sectional imaging (multidetector CT, MRI with special sequences
      and different contrast agents and MR cholangiopancreatography) in combination
      with the clinical history usually enable a non-invasive diagnosis. Pathognomonic
      morphological and hemodynamic lesion features, as well as a knowledge of the
      pathomechanisms, help to differentiate this broad spectrum of entities.
      ACHIEVEMENTS: In this article the different entities of cystic liver lesions,
      together with the appropriate diagnostic method for detection and distinction and
      including their strengths and limitations, are demonstrated. PRACTICAL
      RECOMMENDATIONS: A well-founded knowledge about the development of various cystic
      liver lesions and the suitable choice of imaging method facilitate a non-invasive
      diagnosis.

PMID- 25575723
TI  - [Focal nodular hyperplasia and hepatocellular adenoma].
AB  - CLINICAL ISSUE: Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA)
      are liver lesions of hepatocellular origin. The FNH is a commonly occurring
      hepatic lesion whereas HCA is very rare. Non-invasive differentiation between HCA
      subtypes and atypical FNH may pose a diagnostic challenge as both entities
      predominantly occur in middle-aged female patients. STANDARD RADIOLOGICAL
      METHODS: The conventional imaging modalities include ultrasound (US), computed
      tomography (CT) and magnetic resonance imaging (MRI). Distinguishing FNH from HCA
      is of great importance clinically as FNH is considered to be a benign lesion and
      needs no further management. In contrast HCA is considered to be a borderline
      tumor due to the risk of hemorrhage, growth and even malignant transformation and
      requires individualized management. METHODOLOGICAL INNOVATIONS: The above
      mentioned radiological procedures usually enable an accurate and certain
      diagnosis of a typical FNH to be achieved. In cases of atypical FNH, particularly
      in patients with a clinical history of malignancy, these imaging modalities are
      insufficient to establish a clear diagnosis. In this scenario, the use of modern
      hepatobiliary contrast-enhanced MRI will enable a differentiation between FNH and
      metastasis with a high sensitivity and specificity. Furthermore, it allows a
      differentiation of FNH from 90 % of adenoma subtypes. ACHIEVEMENTS: This article
      describes the histopathological and radiological features of these lesions and
      explains the advantages and limitations of various imaging modalities used for
      the diagnosis and differentiation of these entities. PRACTICAL RECOMMENDATIONS:
      The new classification of HCAs according to phenotype and genotype and their
      imaging features, as well as different enhancement patterns, are described. The
      correlation between HCA subtypes and their individual management are also
      discussed.

PMID- 25575724
TI  - [Primary liver tumors : hepatocellular versus intrahepatic cholangiocellular
      carcinoma].
AB  - CLINICAL ISSUE: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocellular
      carcinoma (ICC) are the most commonly occurring and important primary liver
      tumors. Originating from one pluripotent liver stem cell both tumor entities can
      occur in a cirrhotic liver and also in patients without cirrhosis. Several risk
      factors have been identified as causative for both carcinomas; therefore, tumor
      screening is advantageous, especially for high-risk patients who could be
      diagnosed in an early stage to allow curative treatment. Surgical resection,
      interventional procedures and transplantation are available as curative treatment
      options when diagnosed in time. STANDARD RADIOLOGICAL METHODS: Common
      characteristic features and morphology in cross-sectional imaging by ultrasound
      (US), multidetector computed tomography (CT) and magnetic resonance imaging (MRI)
      as well as screening aspects are presented and discussed. METHODICAL INNOVATIONS:
      Recent findings show a better understanding of the carcinogenesis model of both
      liver tumors originating from one pluripotent liver stem cell. Further
      developments of modern cross-sectional imaging modalities, especially MRI in
      combination with diffusion-weighted imaging and intravenous administration of
      hepatocyte-specific contrast agents enable early detection, exact
      differentiation, staging and treatment evaluation of HCC and ICC ACHIEVEMENTS: In
      this article we discuss modern, multiparametric imaging modalities, which allow a
      complete and reliable diagnosis of the majority of these tumor entities.
      PRACTICAL RECOMMENDATIONS: Contrast-enhanced MRI, using hepatocyte-specific
      contrast agents, is currently the most accurate procedure for the noninvasive
      diagnosis and treatment evaluation of HCC and ICC.

PMID- 25575725
TI  - Methotrexate-mediated activation of an AMPK-CREB-dependent pathway: a novel
      mechanism for vascular protection in chronic systemic inflammation.
AB  - AIMS: Premature cardiovascular events complicate chronic inflammatory conditions.
      Low-dose weekly methotrexate (MTX), the most widely used disease-modifying drug
      for rheumatoid arthritis (RA), reduces disease-associated cardiovascular
      mortality. MTX increases intracellular accumulation of adenosine monophosphate
      (AMP) and 5-aminoimidazole-4-carboxamide ribonucleotide which activates AMP
      activated protein kinase (AMPK). We hypothesised that MTX specifically protects
      the vascular endothelium against inflammatory injury via induction of AMPK
      regulated protective genes. METHODS/RESULTS: In the (NZW*BXSB)F1 murine model of
      inflammatory vasculopathy, MTX 1 mg/kg/week significantly reduced intramyocardial
      vasculopathy and attenuated end-organ damage. Studies of human umbilical vein
      endothelial cells (HUVEC) and arterial endothelial cells (HAEC) showed that
      therapeutically relevant concentrations of MTX phosphorylate AMPKalpha(Thr172),
      and induce cytoprotective genes including manganese superoxide dismutase (MnSOD)
      and haem oxygenase-1 (HO-1). These responses were preserved when HUVECs were
      pretreated with tumour necrosis factor-alpha to mimic dysfunctional endothelium.
      Furthermore, MTX protected against glucose deprivation-induced endothelial
      apoptosis. Mechanistically, MTX treatment led to cyclic AMP response element
      binding protein (CREB)(Ser133) phosphorylation, while AMPK depletion attenuated
      this response and the induction of MnSOD and HO-1. CREB siRNA inhibited
      upregulation of both cytoprotective genes by MTX, while chromatin
      immunoprecipitation demonstrated CREB binding to the MnSOD promoter in MTX
      treated EC. Likewise, treatment of (NZW*BXSB)F1 mice with MTX enhanced
      AMPKalpha(Thr172) phosphorylation and MnSOD, and reduced aortic intercellular
      adhesion molecule-1 expression. CONCLUSIONS: These data suggest that MTX
      therapeutically conditions vascular endothelium via activation of AMPK-CREB. We
      propose that this mechanism contributes to the protection against cardiovascular
      events seen in patients with RA treated with MTX.

PMID- 25575726
TI  - Anti-GAD Antibody, Seizures, Cerebellar Ataxias and Vitiligo: A Diagnostic
      Challenge.

PMID- 25575727
TI  - Mini-Review: Effects of Ethanol on GABAA Receptor-Mediated Neurotransmission in
      the Cerebellar Cortex--Recent Advances.
AB  - Studies from several laboratories have shown that ethanol impairs cerebellar
      function, in part, by altering GABAergic transmission. Here, we discuss recent
      advances in our understanding of the acute effects of ethanol on GABA(A) receptor
      mediated neurotransmission at cerebellar cortical circuits, mainly focusing on
      electrophysiological studies with slices from laboratory animals. These studies
      have shown that acute ethanol exposure increases GABA release at molecular layer
      interneuron-to-Purkinje cell synapses and also at reciprocal synapses between
      molecular layer interneurons. In granule cells, studies with rat cerebellar
      slices have consistently shown that acute ethanol exposure both potentiates tonic
      currents mediated by extrasynaptic GABA(A) receptors and also increases the
      frequency of spontaneous inhibitory postsynaptic currents mediated by synaptic
      GABA(A) receptors. These effects have been also documented in some granule cells
      from mice and nonhuman primates. Currently, there are two distinct models on how
      ethanol produces these effects. In one model, ethanol primarily acts by directly
      potentiating extrasynaptic GABA(A) receptors, including a population that excites
      granule cell axons and stimulates glutamate release onto Golgi cells. In the
      other model, ethanol acts indirectly by increasing spontaneous Golgi cell firing
      via inhibition of the Na(+)/K(+) ATPase, a quinidine-sensitive K(+) channel, and
      neuronal nitric oxide synthase. It was also demonstrated that a direct inhibitory
      effect of ethanol on tonic currents can be unmasked under conditions of low
      protein kinase C activity. In the last section, we briefly discuss studies on the
      chronic effect of ethanol on cerebellar GABA(A) receptor-mediated transmission
      and highlight potential areas where future research is needed.

PMID- 25575728
TI  - Effect of montelukast on clinical score and cytokine levels of infants for
      clinically diagnosed acute bronchiolitis.
AB  - BACKGROUND: Acute bronchiolitis comprises a major cause for morbidity in infants
      with viral infection which induces an immune inflammatory response that may
      produce long lasting harmful effects. Currently, there is no effective therapy
      for bronchiolitis. OBJECTIVE: Our aim was to investigate the efficacy of five-day
      montelukast therapy in acute bronchiolitis management. METHODS: The study
      included 50 infants with acute bronchiolitis. The infants with first episode of
      acute bronchiolitis were randomly assigned to receive daily montelukast dose of
      4mg over five days after admission or no treatment. Plasma eotaxin, IL-4, IL-8
      and IFN-gamma levels were evaluated before and after treatment by ELISA method.
      In the present study, the primary outcome measure was change in clinical severity
      score, whilst secondary outcome measures were changes in plasma eotaxin, IL-4, IL
      8, IFN-gamma levels. RESULTS: No significant differences was found in clinical
      severity score with five-day montelukast treatment (p>0.05, Mann-Whitney U test).
      There were no significant differences in plasma eotaxin, IL-4, IL-8, IFN-gamma
      levels between the groups (p>0.05 Mann-Whitney U test). There was significant
      decrease in plasma IFN-gamma levels following five-day montelukast treatment
      (p=0.027, Wilcoxon). There were no significant differences in plasma IL-4, IL-8,
      IFN-gamma levels between the groups after five-day montelukast treatment (p>0.05,
      Wilcoxon). There was significant increase in eotaxin levels after five-day
      montelukast treatment (p=0.009, Wilcoxon). CONCLUSION: Our study showed that
      montelukast affected plasma IFN-gamma and eotaxin levels after five days of
      treatment. Further studies are needed to demonstrate effects of montelukast on
      chemokine levels in bronchiolitis.

PMID- 25575729
TI  - The Association of ASA Class on Total Knee and Total Hip Arthroplasty Readmission
      Rates in an Academic Hospital.
AB  - Total hip and knee arthroplasties are two of the most successful orthopaedic
      procedures. However, with the increasing demand, estimated future costs for these
      procedures are enormous. Recent data suggest post-discharge care may account for
      up to 35% of total episode payments. Yet, little is known about targets that can
      help improve quality and reduce cost. This retrospective study shows an ASA score
      of >= 3 is associated with a 2.9 times (P = 0.0082) greater risk of re-admission
      in total joint arthroplasty patients. The current literature corroborates this
      finding by demonstrating an increase risk of post-operative complications in
      patients with an ASA of >= 3. Therefore, the ASA score is a potential target for
      interventions designed to increase quality and lower cost in arthroplasty
      patients.

PMID- 25575730
TI  - Medial over-resection of the tibia in total knee arthroplasty for varus deformity
      using computer navigation.
AB  - We are reporting a series of 35 cases in which downsizing, lateralizing of the
      tibial baseplate and resection of the uncovered medial plateau bone releases the
      medial collateral ligament and tightens the lateral collateral ligament. Result
      in excellent ligamentous balance and correction to neutral mechanical axis. The
      mean follow up was 32.8 months (11-95 months) and the average pre-operative varus
      was 9.47 degrees  (3.5-15 degrees ) with the average post-operative alignment was
      0.65 degrees  varus. We obtained a mean correction of 0.45 degrees  for every mm
      (millimeter) of bone resected. We did not have any varus collapse or instability.
      Medial Over-resection could be employed as a technique in the management of varus
      OA knee with 2mm of resection giving about 10 correction of deformity.

PMID- 25575731
TI  - Studies of the photosensitizer disulfonated meso-tetraphenyl chlorin in an
      orthotopic rat bladder tumor model.
AB  - BACKGROUND: Photochemical internalization (PCI) is a novel technology for the
      release of a therapeutic molecule from endocytic vesicles into the cytosol of a
      cell. The release of molecules occurs after activation of an endocytic membrane
      embedded photosensitizer by light. In this study uptake and localization of the
      photosensitizer disulfonated tetraphenyl chlorin (TPCS2a) were explored to
      optimize a PCI protocol in an orthotopic rat bladder tumor model. METHODS: Female
      Fischer F344 rats were intravesically instilled with 0.4*10(6) AY-27 transitional
      carcinoma cells before allowing tumor growth for 14 days. The photosensitizer
      TPCS2a was intravesically instilled at different concentrations, and bladders
      were excised after different time intervals. The retention, penetration, and
      localization of intratumoral TPCS2a were explored ex vivo using fluorescence
      spectroscopy and fluorescence microscopy to determine an optimal PCI protocol.
      These results were compared to histological analysis of necrotic areas after
      activation of intratumoral TPCS2a by red light (652nm, 0.5J/cm(2)). RESULTS: A
      superficial distribution pattern of the photosensitizer TPCS2a was seen in
      bladder tumor tissue, and TPCS2a was almost cleared from the tumors after 72h.
      The highest retention of TPCS2a was found at 24h after instillation when using a
      concentration of 3mg/ml. CONCLUSION: An optimal PCI protocol was defined for the
      tumor model, including a 24-h TPCS2a-to-light interval and a dose of 3mg/ml
      TPCS2a. This protocol will be utilized for the study of PCI-enhanced therapeutic
      effects on non-muscle invasive bladder cancer, using a potent chemotherapeutic
      under an optimal light dose.

PMID- 25575732
TI  - Characterization and colonization of endomycorrhizal Rhizoctonia fungi in the
      medicinal herb Anoectochilus formosanus (Orchidaceae).
AB  - The medicinal effects and techniques for cultivating Anoectochilus formosanus are
      well-documented, but little is known about the mycorrhizal fungi associated with
      A. formosanus. Rhizoctonia (Thanatephorus) anastomosis group 6 (AG-6) was the
      most common species isolated from fungal pelotons in native A. formosanus and
      represented 67% of the sample. Rhizoctonia (Ceratobasidium) AG-G, P, and R were
      also isolated and represent the first occurrence in the Orchidaceae. Isolates of
      AG-6, AG-R, and AG-P in clade I increased seed germination 44-91% and promoted
      protocorm growth from phases III to VI compared to asymbiotic treatments and
      isolates of AG-G in clade II and Tulasnella species in clade III. All isolates in
      clades I to III formed fungal pelotons in tissue-cultured seedlings of A.
      formosanus, which exhibited significantly greater growth than nonmycorrhizal
      seedlings. An analysis of the relative effect of treatment ([Formula: see text])
      showed that the low level of colonization ([Formula: see text]) by isolates in
      clade I resulted in a significant increase in seedling growth compared to
      isolates in clades II (0.63-0.82) and III (0.63-0.75). There was also a negative
      correlation (r = -0.8801) with fresh plant weight and fungal colonization. Our
      results suggest that isolates in clade I may represent an important group
      associated with native populations of A. formosanus and can vary in their ability
      to establish a symbiotic association with A. formosanus. The results presented
      here are potentially useful for advancing research on the medicinal properties,
      production, and conservation of A. formosanus in diverse ecosystems.

PMID- 25575733
TI  - Artemisinin inhibits the proliferation, migration, and inflammatory reaction
      induced by tumor necrosis factor-alpha in vascular smooth muscle cells through
      nuclear factor kappa B pathway.
AB  - BACKGROUND: Atherosclerosis is an inflammatory disease with the most common
      pathologic process leading to cardiovascular diseases. The aim of this study was
      to evaluate the effect of artemisinin (ART) on the proliferation, migration, and
      inflammation induced by tumor necrosis factor-alpha (TNF-alpha) of rat vascular
      smooth muscle cells (VSMCs). MATERIALS AND METHODS: Primary rat VSMCs were
      pretreated with ART and then co-incubated with TNF-alpha. Cell proliferation was
      evaluated by MTT assay. Cell migration was assessed by transwell assay. Reactive
      oxygen species (ROS) production was measured by flow cytometry after staining
      with dichloro-dihydro-fluorescein diacetate. Inflammation factors of nitric oxide
      and prostaglandin E2 (PGE2) were measured by responding assay kits. Expression
      levels of nuclear factor kappa B (NF-kappaB) subunit NF-kappaB p65 and the
      regulator inhibitor of nuclear factor kappa-B kinase-alpha (IkappaBalpha) were
      tested by Western blot, meanwhile, the activation of NF-kappaB was observed by
      immunofluorescence assay. RESULTS: The proliferation, migration, and inflammation
      of VSMCs induced by TNF-alpha were significantly inhibited by ART treatment in a
      dose-dependent manner. Treatment with 100 MUM ART for 2 h significantly reduced
      the expression of proliferating cell nuclear antigen and migration-related
      proteins matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP
      9). On the other hand, the same treatment decreased the inflammation factors
      production of nitric oxide and PGE2. Fluorescence-activated cell sorting analysis
      revealed that ART suppressed the ROS production induced by TNF-alpha. Western
      blot analysis showed that both inflammation mediators inducible nitric oxide
      synthase and cyclooxygenase and the NF-kappaB pathway subunit NF-kappaB p65 were
      downregulated by ART. CONCLUSIONS: The results suggest that ART can effectively
      inhibit the proliferation, migration, and inflammation of VSMCs induced by TNF
      alpha through ROS-mediated NF-kappaB signal pathway.

PMID- 25575734
TI  - Neutrophil extracellular traps contribute to the intestine damage in endotoxemic
      rats.
AB  - BACKGROUND: Sepsis is one of the most troublesome problems in critically ill
      patients and often accompanied with multiple organ dysfunction and high
      mortality. Gut injury or dysfunction may contribute to the pathogenesis of
      sepsis. Neutrophil extracellular traps (NETs) do not only kill microorganisms but
      also damage host cells during inflammatory response to infection. The aim of this
      study was to investigate whether NETs are capable of promoting the impairment of
      the gut in a rat model of lipopolysaccharide (LPS)-induced sepsis. METHODS: The
      sepsis model was induced in rats by intraperitoneal injection of LPS (10 mg/kg).
      All rats were divided into three groups as follows: 1) control group; 2) LPS
      group; and 3) LPS + DNase I group. The DNase I solution (10 mg/kg) was injected
      intravenously to disrupt NETs 30 min after the LPS treatment. The animals were
      sacrificed at 3 h and 24 h after LPS or saline challenge. The intestinal cell
      apoptosis was examined by detecting the level of cleaved caspase-3 and terminal
      deoxynucleotidyl transferase dUTP nick-end labeling assays. The length and
      morphology of Villi were assessed histologically through hematoxylin and eosin
      stain. The levels of tumor necrosis factor-alpha and interleukin-10 in serum and
      intestine were detected by enzyme-linked immunosorbent assay. Intestinal injury
      was evaluated with Chiu scoring system. RESULTS: A large number of neutrophils
      infiltrated were activated to release NETs in the intestine of LPS-induced septic
      rats. The disruption of NETs reduced the acute systemic inflammatory response and
      apoptosis of intestinal epithelial cells and alleviated histologic pathogenesis.
      Removal of NETs provided a beneficial effect on intestinal injury. CONCLUSIONS:
      This study demonstrates that the release of NETs may contribute to the intestinal
      damage during sepsis.

PMID- 25575735
TI  - Urgent endovascular ligature of a ruptured splenic artery pseudoaneurysm in a
      patient with acute pancreatitis: a case report.
AB  - INTRODUCTION: We report on the successful endovascular treatment of a ruptured
      splenic artery pseudoaneurysm. Our patient had acute pancreatitis superimposed on
      chronic calcific pancreatitis and chronic renal impairment. Contrast-enhanced
      ultrasonography was used to assess post-embolization results. CASE PRESENTATION:
      Our patient was a 67-year-old white Caucasian man with recurrent pancreatitis.
      Computed tomography angiography showed a pancreatic pseudocyst with a ruptured
      pseudoaneurysm, which was successfully embolized using an endovascular
      percutaneous approach. At six months, persistent renal failure led to contrast
      enhanced ultrasonography. This confirmed the absence of turbulent blood flow and
      extravasation of contrast medium in the pseudocyst. CONCLUSION: Our experience
      with this case leads us to support the role of interventional radiology as a
      first-line treatment tool. Contrast-enhanced ultrasonography can be used to
      follow-up embolization procedures in patients with impaired renal function.

PMID- 25575736
TI  - Prion-like features of misfolded Abeta and tau aggregates.
AB  - Recent findings have shown that several misfolded proteins can transmit disease
      pathogenesis in a prion-like manner by transferring their conformational
      properties to normally folded units. However, the extent by which these molecule
      to-molecule or cell-to-cell spreading processes reflect the entire prion behavior
      is now subject of controversy, especially due to the lack of epidemiological data
      supporting inter-individual transmission of non-prion protein misfolding
      diseases. Nevertheless, extensive research has shown that several of the typical
      characteristics of prions can be observed for Abeta and tau aggregates when
      administered in animal models. In this article we review recent studies
      describing the prion-like features of both proteins, highlighting the
      similarities with bona fide prions in terms of inter-individual transmission,
      their strain-like conformational diversity, and the transmission of misfolded
      aggregates by different routes of administration. 

PMID- 25575737
TI  - Plumage pigment differences underlying the yellow-red differentiation in the
      Northern Flicker (Colaptes auratus).
AB  - Elucidating the processes that create species differences is a central goal of
      evolutionary biology. The Northern Flicker (Colaptes auratus) exists as two well
      differentiated subspecies groups in North America, the Yellow-shafted (auratus
      group) and Red-shafted Flickers (cafer group), which differ strikingly in the
      color of the underside and rachises of flight feathers, and of malar and nuchal
      patches. We investigated the physiological basis of these conspicuous phenotypic
      differences by identifying and quantifying the pigments involved. The yellow
      feathers of auratus contained carotenoids commonly found in nature (lutein, beta
      cryptoxanthin, zeaxanthin and beta-carotene). The orange to red shafts/vanes of
      cafer and hybrids contained these carotenoids as well as mono- and diketo
      carotenoids (notably adonirubin, alpha-doradexanthin, canthaxanthin,
      astaxanthin), representing oxygenated products at carbon C4(4') of the
      carotenoids present in auratus. Oxygenation of feather carotenoids at C4(4')
      correlated closely with shaft/vane redness. Carotenoid hydroxylation at C3(3')
      and the proportion of carotenoids with epsilon end-rings also varied with color
      and belie differences in the activity of several carotenoid-modifying enzymes
      between the two subspecies groups. Curiously, occasional yellow feathers in red
      shafted individuals had the carotenoids of auratus, hence the differences are not
      constitutive in cafer, underscoring regulatory differences. The red malar stripe
      of cafer, the black malar stripe and red nuchal patch of auratus all contained
      similar types and amounts of carotenoids, mostly 3-hydroxy-4-keto-carotenoids.
      The biochemical differences between two strongly differentiated forms we
      uncovered shed light on how plumage coloration can change over evolutionary time
      and point to further avenues of research. 

PMID- 25575738
TI  - Molecular characterization of betaine-homocysteine methyltransferase 1 from the
      liver, and effects of aestivation on its expressions and homocysteine
      concentrations in the liver, kidney and muscle, of the African lungfish,
      Protopterus annectens.
AB  - Homocysteine accumulation has numerous deleterious effects, and betaine
      homocysteine S-methyltransferase (BHMT) catalyses the synthesis of methionine
      from homocysteine and betaine. This study aimed to determine homocysteine
      concentrations, and mRNA expression levels and protein abundances of bhmt1/Bhmt1
      in the liver, kidney and muscle of the African lungfish, Protopterus annectens,
      during the induction (6 days), maintenance (6 months) or arousal (3 days after
      arousal) phase of aestivation. The homocysteine concentration decreased
      significantly in the liver of P. annectens after 6 days or 6 months of
      aestivation, but it returned to the control level upon arousal. By contrast,
      homocysteine concentrations in the kidney and muscle remained unchanged during
      the three phases of aestivation. The complete coding cDNA sequence of bhmt1 from
      P. annectens consisted of 1236 bp, coding for 412 amino acids. The Bhmt1 from P.
      annectens had a close phylogenetic relationship with those from tetrapods and
      Callorhinchus milii. The expression of bhmt1 was detected in multiple
      organs/tissues of P. annectens, and this is the first report on the expression of
      bhmt1/Bhmt1 in animal skeletal muscle. The mRNA and protein expression levels of
      bhmt1/Bhmt1 were up-regulated in the liver of P. annectens during the induction
      and maintenance phases of aestivation, possibly to regulate the hepatic
      homocysteine concentration. The significant increase in hepatic Bhmt1 protein
      abundance during the arousal phase could be a response to increased cellular
      methylation for the purpose of tissue reconstruction. Unlike the liver, Bhmt1
      expression in the kidney and muscle of P. annectens was regulated
      translationally, and its up-regulation could be crucial to prevent homocysteine
      accumulation.

PMID- 25575739
TI  - Phenotypic variability in gap junction syndromic skin disorders: experience from
      KID and Clouston syndromes' clinical diagnostics.
AB  - Connexins belong to the family of gap junction proteins which enable direct cell
      to-cell communication by forming channels in adjacent cells. Mutations in
      connexin genes cause a variety of human diseases and, in a few cases, result in
      skin disorders. There are significant differences in the clinical picture of two
      rare autosomal dominant syndromes: keratitis-ichthyosis-deafness (KID) syndrome
      and hidrotic ectodermal dysplasia (Clouston syndrome), which are caused by GJB2
      and GJB6 mutations, respectively. This is despite the fact that, in both cases,
      malfunctioning of the same family proteins and some overlapping clinical features
      (nail dystrophy, hair loss, and palmoplantar keratoderma) is observed. KID
      syndrome is characterized by progressive vascularizing keratitis, ichthyosiform
      erythrokeratoderma, and neurosensory hearing loss, whereas Clouston syndrome is
      characterized by nail dystrophy, hypotrichosis, and palmoplantar keratoderma. The
      present paper presents a Polish patient with sporadic KID syndrome caused by the
      mutation of p.Asp50Asn in GJB2. The patient encountered difficulties in obtaining
      a correct diagnosis. The other case presented is that of a family with Clouston
      syndrome (caused by p.Gly11Arg mutation in GJB6), who are the first reported
      patients of Polish origin suffering from this disorder. Phenotype diversity among
      patients with the same genotypes reported to date is also summarized. The
      conclusion is that proper diagnosis of these syndromes is still challenging and
      should always be followed by molecular verification.

PMID- 25575740
TI  - Computational Modelling of Multi-folded Balloon Delivery Systems for Coronary
      Artery Stenting: Insights into Patient-Specific Stent Malapposition.
AB  - Despite the clinical effectiveness of coronary artery stenting, percutaneous
      coronary intervention or "stenting" is not free of complications. Stent
      malapposition (SM) is a common feature of "stenting" particularly in challenging
      anatomy, such as that characterized by long, tortuous and bifurcated segments. SM
      is an important risk factor for stent thrombosis and recently it has been
      associated with longitudinal stent deformation. SM is the result of many factors
      including reference diameter, vessel tapering, the deployment pressure and the
      eccentric anatomy of the vessel. For the purpose of the present paper, virtual
      multi-folded balloon models have been developed for simulated deployment in both
      constant and varying diameter vessels under uniform pressure. The virtual
      balloons have been compared to available compliance charts to ensure realistic
      inflation response at nominal pressures. Thereafter, patient-specific simulations
      of stenting have been conducted aiming to reduce SM. Different scalar indicators,
      which allow a more global quantitative judgement of the mechanical performance of
      each delivery system, have been implemented. The results indicate that at
      constant pressure, the proposed balloon models can increase the minimum stent
      lumen area and thereby significantly decrease SM. 

PMID- 25575741
TI  - Gene expression profile of high-fat diet-fed C57BL/6J mice: in search of
      potential role of azelaic acid.
AB  - High-fat diet (HFD) elevates circulatory fatty acids and influences glucose and
      fat metabolism. Azelaic acid (AzA), a naturally occurring alpha,omega
      dicarboxylic acid in wheat, rye, barley, oat seeds and sorghum, has been reported
      to exert antidiabetic effects in HFD-induced type 2 diabetes mellitus (T2DM)
      C57BL/6J mice. The present study was undertaken to identify the genes that are
      differentially modulated by treatment with AzA in HFD-fed mice. Mice were fed HFD
      for 10 weeks and subjected to intragastric administration of 80 mg/kg body weight
      (BW) of AzA daily along with HFD from 11 to 15 weeks. Lipid profile, adipokines
      and cytokines were examined in the plasma/liver of mice. Whole genome profiling
      was performed in the liver of mice using microarray and validated by qRT-PCR,
      Western blot and immunohistochemical analyses. HFD intake resulted in
      significantly elevated lipids (except high-density lipoproteins), resistin,
      tumour necrosis factor alpha and interleukin-6 with marked reduction in
      adiponectin. Administration of AzA to HFD-fed mice significantly restored the
      lipids, adipokines and cytokines to near normal. Transcript profiling revealed
      that HFD intake activated the genes involved in stress response, cell cycle
      regulation and apoptosis. Treatment with AzA caused increased expression of genes
      involved in reactive oxygen species (ROS) scavenging, receptor-mediated
      signalling, transcription, protein modification and insulin signal transduction.
      AzA activates insulin signal molecules leading to insulin sensitivity. The
      ability of AzA to modulate the expression of these genes supports the notion that
      AzA is a promising drug candidate for the treatment of insulin resistance
      associated with T2DM.

PMID- 25575742
TI  - High rate of unnecessary thymectomy and its cause. Can computed tomography
      distinguish thymoma, lymphoma, thymic hyperplasia, and thymic cysts?
AB  - PURPOSE: To determine the non-therapeutic thymectomy rate in a recent six-year
      consecutive thymectomy cohort, the etiology of these unnecessary thymectomies,
      and the differentiating CT features of thymoma, lymphoma, thymic hyperplasia, and
      thymic cysts. MATERIALS AND METHODS: Electronic data base query of all
      thymectomies performed at the Massachusetts General Hospital from 2006 to 2012
      yielded 160 thymectomy cases, 124 of which had available imaging. The non
      therapeutic thymectomy rate (includes thymectomy for lymphoma and benign disease)
      was calculated. Preoperative clinical and CT imaging features were assessed by
      review of the in-house electronic medical record by 2 thoracic surgeons and 2
      pathology-blinded radiologists, respectively. RESULTS: The non-therapeutic
      thymectomy rate of 43.8% (70/160) was largely secondary to concern for thymoma
      and was comprised of lymphoma (54.3%, 38/70), thymic bed cysts (24.3%, 17/70),
      thymic hyperplasia (17.1%, 12/70), and reactive or atrophic tissue (4.3%, 3/70).
      Among these four lesions, there were significant differences in location with
      respect to midline, morphology, circumscription, homogeneity of attenuation,
      fatty intercalation, coexistent lymphadenopathy, overt pericardial invasion, and
      mass effect (p<0.001). True thymic cysts ranged in attenuation from -20 to
      58Hounsfield units (HU), with a mean attenuation of 23HU. CONCLUSION: The high
      rate of unnecessary thymectomy was due to misinterpretation of thymic cysts,
      thymic hyperplasia, and lymphoma as thymoma on chest CT. This study demonstrates
      differentiating features between thymoma, lymphoma, thymic hyperplasia, and
      thymic cysts on chest CT which may help triage more patients away from thymectomy
      toward less invasive and non-invasive means of diagnosis and thereby lower the
      non-therapeutic thymectomy rate.

PMID- 25575743
TI  - Drug-eluting versus plain balloon angioplasty for the treatment of failing
      dialysis access: final results and cost-effectiveness analysis from a prospective
      randomized controlled trial (NCT01174472).
AB  - OBJECTIVE: To report the final results and cost-effectiveness analysis of a
      prospective randomized controlled trial investigating drug-eluting balloon (DEB)
      versus plain balloon angioplasty (BA) for the treatment of failing dialysis
      access (NCT01174472). METHODS: 40 patients were randomized to angioplasty with
      either DEB (n=20) or BA (n=20) for treatment of significant venous stenosis
      causing a failing dialysis access. Both arteriovenous fistulas (AVF) and
      synthetic arteriovenous grafts (AVG) were included. Angiographic follow up was
      scheduled every two months. Primary endpoints were technical success and target
      lesion primary patency at 1 year. Cumulative and survival analysis was performed.
      Incremental net benefit (INB) and incremental cost effectiveness ratio (ICER)
      were calculated and the cost-effectiveness acceptability curve (CEAC) was drawn.
      RESULTS: Baseline variables were equally distributed between the two groups. At 1
      year, cumulative target lesion primary patency was significantly higher after DEB
      application (35% vs. 5% after BA, p<0.001). Overall, median primary patency was
      0.64 years in case of DEB vs. 0.36 years in case of BA (p=0.0007; unadjusted
      HR=0.27 [95%CI: 0.13-0.58]; Cox adjusted HR=0.23 [95%CI: 0.10-0.50]). ICER was
      2198 Euros (?) per primary patency year of dialysis access gained. INB was 1068?
      (95%CI: 31-2105?) for a willingness-to-pay (WTP) threshold of 5000?
      (corresponding acceptability probability >97%). CONCLUSION: DEB angioplasty may
      be a cost-effective option that significantly improves patency after angioplasty
      of venous stenoses of failing vascular dialysis access. Further large-scale
      randomized trials are warranted.

PMID- 25575744
TI  - Coupled equilibria of a self-associating drug loaded into polymeric
      nanoparticles.
AB  - Doxorubicin (DOX) and other anti-cancer drugs are often formulated using
      nanoparticles for passive or active targeting and reducing detrimental side
      effects. Anionic polymers have been shown to effectively facilitate loading of
      cationic DOX hydrochloride into nanoparticles with high efficiency. One powerful
      method to study DOX loading into anionic polymeric nanoparticles has been
      isothermal titration calorimetry (ITC), but the curves are complex and were
      previously interpreted in a largely qualitative manner only. Here we present
      detailed quantitative modelling of such ITC data, corroborated by zeta potential
      measurements and dynamic light scattering. The model takes into account 3 coupled
      equilibria. First, DOX self-associates in solution to dimers and larger
      aggregates. This effect is modelled in terms of the stepwise aggregation model.
      Second, DOX binds with a 1:1 stoichiometry to the carboxylic acids in the polymer
      at low salt. At about 33% saturation, the nanoparticles collapse in size and the
      enthalpy of further binding becomes less exothermic. Third, free DOX also stacks
      onto polymer-bound DOX. This stacking effect is very weak and hardly detected by
      ITC. It is, however, revealed by a positive zeta potential. The present work
      demonstrates the power of combining ITC with light scattering and zeta potential
      measurements for studying the thermodynamics of drug loading into polymeric
      nanoparticles. 

PMID- 25575745
TI  - Measurement of anti-Mullerian hormone: performances of a new ultrasensitive
      immunoassay.
AB  - The measurement of anti-Mullerian hormone (AMH) is relevant for the evaluation of
      primary ovarian insufficiency, success of assisted reproductive therapies, and
      also to support the diagnosis of polycystic ovary syndrome. Our study
      demonstrated excellent analytical performances for the Ansh Laboratories AMH
      immunoassay and an overall good agreement with the AMH Gen II assay.
      Nevertheless, the two AMH immunoassays are not using the same couple of
      antibodies and therefore not commutable and the definition of specific reference
      values and cut-point remains necessary. 

PMID- 25575746
TI  - Three-dimensional endothelial cell morphogenesis under controlled ion release
      from copper-doped phosphate glass.
AB  - Copper ions represent a promising angiogenic agent but are associated with
      cytotoxicity at elevated concentrations. Phosphate-based glasses (PGs) exhibit
      adjustable dissolution properties and allow for controlled ion release. This
      study examined the formation of capillary-like networks by SVEC4-10 endothelial
      cells (ECs) seeded in a three-dimensional (3D) type I collagen hydrogel matrix
      mixed with PG particles of the formulation 50P2O5-30CaO-(20-x)Na2O-xCuO (x=0 and
      10 mol%). Copper and total phosphorus release decreased over time and was more
      sustained in the case of 10% CuO PG. Moreover, increasing the concentration of
      10% CuO PG in collagen substantially delayed dissolution along with preferential
      release of copper. A 3D morphometric characterization method based on confocal
      laser scanning microscopy image stacks was developed in order to quantify EC
      network length, connectivity and branching. Network length was initially reduced
      in a concentration-dependent fashion by 10% CuO PG and, to a lesser extent, by 0%
      CuO PG, but reached values identical to the non-PG control by day 5 in culture.
      This reduction was attributed to a PG-mediated decrease in cell metabolic
      activity while cell proliferation as well as network connectivity and branching
      were independent of PG content. Gene expression of matrix metalloproteinases
      (MMP)-1 and -2 was up-regulated by PGs, indicating that MMPs did not play a
      critical role in network growth. The relationship between ion release and EC
      morphogenesis in 3D provided in this study is expected to contribute to an
      ultimately successful pro-angiogenic application of CuO-doped PGs.

PMID- 25575747
TI  - Can two-dimensional measured peak sagittal plane excursions during drop vertical
      jumps help identify three-dimensional measured joint moments?
AB  - BACKGROUND: Less optimal sagittal plane movement patterns are believed to
      increase knee injury risk in female athletes. To facilitate clinical screening
      with a user-friendly method, the purpose of the present study was to examine the
      temporal relationships between two-dimensional measured sagittal plane kinematics
      and three-dimensional joint moments during the double-leg drop vertical jump
      (DVJ) and single-leg DVJ (SLDVJ). METHODS: Fifty injury-free female athletes were
      tested. Maximal excursions of hip flexion, knee flexion and ankle dorsiflexion
      were measured through two-dimensional video analysis. Three-dimensional motion
      and ground reaction forces were recorded to calculate external hip flexion, knee
      flexion and knee abduction moments during the entire stance phase of DVJ and
      SLDVJ. One-dimensional statistical parametric mapping was used to examine
      relationships between peak two-dimensional kinematic variables and three
      dimensional moment profiles. RESULTS: Hip flexion was significantly related to
      the hip and knee flexion moment for both tests and knee abduction moment for DVJ
      during the time frames corresponding with highest three-dimensional moments,
      while knee flexion was significantly related to the hip flexion moment during
      these time frames. No significant relationships were found for ankle dorsiflexion
      with any of the joint moments. CONCLUSIONS: Two-dimensional measured sagittal
      plane hip flexion angles at the deepest landing position were associated with
      peak joint moments of the hip and knee during DVJ and SLDVJ, while the amount of
      knee flexion was only associated with the hip flexion moment. Assessment of knee
      injury risk with two-dimensional video analysis could benefit from measuring
      maximal hip flexion, more so than knee flexion.

PMID- 25575748
TI  - Effects of salinity on metal uptake and metallothionein mRNA levels in the organs
      of tilapia exposed to cadmium, copper, and zinc ions.
AB  - This study aimed to determine the effects of salinity on metal uptake and
      metallothionein (MT) mRNA levels in tilapia exposed to three metal ions. Male
      Oreochromis niloticus * O. aureus juveniles (hereafter, "tilapia") were exposed
      to various concentrations (100, 500, and 1 ppm) of metal ions (Cd(2+), Cu(2+) and
      Zn(2+)) in freshwater and water with two levels of salinity (10 and 20 ppt) for 7
      days. Tests were then performed to investigate the effects of salinity on metal
      concentrations and MT mRNA induction in the test subjects' organs. Saline
      decreased cadmium (Cd) uptake and MT mRNA fold induction in various internal
      organs, but it did not enhance MT mRNA induction in the gills. Exposure to Cu(2+)
      caused greater copper (Cu) levels in the brains, intestines and livers, but Cu
      uptake in the intestines and kidneys occurred only at 10 ppm. MT mRNA induction
      caused by Cu(2+) was observed in various internal organs, but it occurred in the
      gills only at greater levels of salinity. Exposure at greater salinities also
      decreased zinc (Zn) uptake and MT mRNA induction in all organs except the gills.
      Although greater salinity decreased Cd and Zn uptake, the metal content in the
      water correlated with the MT mRNA levels in most of the organs, except for the
      intestines. In conclusion, metal accumulations in the livers and kidneys of
      tilapia correlated with MT mRNA levels. The levels of MT mRNA in the livers and
      kidneys of tilapia might therefore be used as biomarkers of exposure to Cd(2+),
      Cu(2+) and Zn(2+) in water of various salinities.

PMID- 25575749
TI  - Epidermal keratinocytes initiate wound healing and pro-inflammatory immune
      responses following percutaneous schistosome infection.
AB  - Keratinocytes constitute the majority of cells in the skin's epidermis, the first
      line of defence against percutaneous pathogens. Schistosome larvae (cercariae)
      actively penetrate the epidermis to establish infection, however the response of
      keratinocytes to invading cercariae has not been investigated. Here we address
      the hypothesis that cercariae activate epidermal keratinocytes to promote the
      development of a pro-inflammatory immune response in the skin. C57BL/6 mice were
      exposed to Schistosoma mansoni cercariae via each pinna and non-haematopoietic
      cells isolated from epidermal tissue were characterised for the presence of
      different keratinocyte sub-sets at 6, 24 and 96 h p.i. We identified an expansion
      of epidermal keratinocyte precursors (CD45(-), CD326(-), CD34(+)) within 24 h of
      infection relative to naive animals. Following infection, cells within the
      precursor population displayed a more differentiated phenotype (alpha6integrin(
      )) than in uninfected skin. Parallel immunohistochemical analysis of pinnae
      cryosections showed that this expansion corresponded to an increase in the
      intensity of CD34 staining, specifically in the basal bulge region of hair
      follicles of infected mice, and a higher frequency of keratinocyte Ki67(+) nuclei
      in both the hair follicle and interfollicular epidermis. Expression of pro
      inflammatory cytokine and stress-associated keratin 6b genes was also transiently
      upregulated in the epidermal tissue of infected mice. In vitro exposure of
      keratinocyte precursors isolated from neonatal mouse skin to excretory/secretory
      antigens released by penetrating cercariae elicited IL-1alpha and IL-1beta
      production, supporting a role for keratinocyte precursors in initiating cutaneous
      inflammatory immune responses. Together, these observations indicate that
      S.mansoni cercariae and their excretory/secretory products act directly upon
      epidermal keratinocytes, which respond by initiating barrier repair and pro
      inflammatory mechanisms similar to those observed in epidermal wound healing.

PMID- 25575750
TI  - Uncertainty, risk analysis and change for Ebola personal protective equipment
      guidelines.

PMID- 25575751
TI  - Unusual parotid swelling: what is the diagnosis?

PMID- 25575752
TI  - Integrating big data and actionable health coaching to optimize wellness.
AB  - The Hundred Person Wellness Project (HPWP) is a 10-month pilot study of 100
      'well' individuals where integrated data from whole-genome sequencing, gut
      microbiome, clinical laboratory tests and quantified self measures from each
      individual are used to provide actionable results for health coaching with the
      goal of optimizing wellness and minimizing disease. In a commentary in BMC
      Medicine, Diamandis argues that HPWP and similar projects will likely result in
      'unnecessary and potential harmful over-testing'. We argue that this new approach
      will ultimately lead to lower costs, better healthcare, innovation and economic
      growth. The central points of the HPWP are: 1) it is focused on optimizing
      wellness through longitudinal data collection, integration and mining of
      individual data clouds, enabling development of predictive models of wellness and
      disease that will reveal actionable possibilities; and 2) by extending this study
      to 100,000 well people, we will establish multiparameter, quantifiable wellness
      metrics and identify markers for wellness to early disease transitions for most
      common diseases, which will ultimately allow earlier disease intervention,
      eventually transitioning the individual early on from a disease back to a
      wellness trajectory.

PMID- 25575753
TI  - Microarray and Co-expression Network Analysis of Genes Associated with Acute
      Doxorubicin Cardiomyopathy in Mice.
AB  - Clinical use of doxorubicin (DOX) in cancer therapy is limited by its dose
      dependent cardiotoxicity. But molecular mechanisms underlying this phenomenon
      have not been well defined. This study was to investigate the effect of DOX on
      the changes of global genomics in hearts. Acute cardiotoxicity was induced by
      giving C57BL/6J mice a single intraperitoneal injection of DOX (15 mg/kg).
      Cardiac function and apoptosis were monitored using echocardiography and TUNEL
      assay at days 1, 3 and 5. Myocardial glucose and ATP levels were measured.
      Microarray assays were used to screen gene expression profiles in the hearts at
      day 5, and the results were confirmed with qPCR analysis. DOX administration
      caused decreased cardiac function, increased cardiomyocyte apoptosis and
      decreased glucose and ATP levels. Microarrays showed 747 up-regulated genes and
      438 down-regulated genes involved in seven main functional categories. Among
      them, metabolic pathway was the most affected by DOX. Several key genes,
      including 2,3-bisphosphoglycerate mutase (Bpgm), hexokinase 2, pyruvate
      dehydrogenase kinase, isoenzyme 4 and fructose-2,6-bisphosphate 2-phosphatase,
      are closely related to glucose metabolism. Gene co-expression networks suggested
      the core role of Bpgm in DOX cardiomyopathy. These results obtained in mice were
      further confirmed in cultured cardiomyocytes. In conclusion, genes involved in
      glucose metabolism, especially Bpgm, may play a central role in the pathogenesis
      of DOX-induced cardiotoxicity. 

PMID- 25575754
TI  - Can probiotics be used to treat allergic diseases?
AB  - Probiotics are proprietary formulations of specific microorganisms and quantified
      populations of live bacteria that are intended to confer a health benefit on the
      host. These different strains and combinations of microorganisms have a wide and
      varying range of clinical and immunologic capacities that can modify intestinal
      microbial populations in ways that can benefit the host. The enhanced presence of
      probiotic bacteria in the intestinal microbiota has been found to correlate with
      protection against atopy. The prevalence of allergic diseases such as asthma,
      allergic rhinitis, and atopic dermatitis has increased sharply over the past 2-3
      decades in many countries, and allergies are now the most common chronic disease
      among children throughout the world. In the past few years, probiotics have been
      advocated for the management of allergic diseases in many parts of the world. So
      far, probiotics have shown more promise, albeit limited, in the primary
      prevention of allergic disease rather than in the treatment of established
      disease. 

PMID- 25575755
TI  - Mental rotation training: transfer and maintenance effects on spatial abilities.
AB  - One of the aims of research in spatial cognition is to examine whether spatial
      skills can be enhanced. The goal of the present study was thus to assess the
      benefit and maintenance effects of mental rotation training in young adults.
      Forty-eight females took part in the study: 16 were randomly assigned to receive
      the mental rotation training (based on comparing pairs of 2D or 3D objects and
      rotation games), 16 served as active controls (performing parallel non-spatial
      activities), and 16 as passive controls. Transfer effects to both untrained
      spatial tasks (testing both object rotation and perspective taking) and visual
      and verbal tasks were examined. Across the training sessions, the group given
      mental rotation training revealed benefits in the time it took to make judgments
      when comparing 3D and 2D objects, but their mental rotation speed did not
      improve. When compared with the other groups, the mental rotation training group
      did show transfer effects, however, in tasks other than those practiced (i.e., in
      object rotation and perspective-taking tasks), and these benefits persisted after
      1 month. The training had no effect on visual or verbal tasks. These findings are
      discussed from the spatial cognition standpoint and with reference to the
      (rotation) training literature.

PMID- 25575756
TI  - The processing difference between person names and common nouns in sentence
      contexts: an ERP study.
AB  - Person names and common nouns differ in how they are stored in the mental
      lexicon. Using event-related potentials, this study compared the integration of
      names and nouns into sentence contexts. Both person names and common nouns were
      highly related in meaning and either congruent or incongruent within the previous
      contexts. Name incongruence elicited an N400 effect, suggesting that people were
      able to rapidly retrieve the semantic meaning of names from long-term memory even
      when this process was mediated by person identification. Conversely, participants
      showed a "good enough" processing of the nouns due to their low specificity level
      and, thus, rich semantic associations, leading to a P600 effect. These
      distinctive ERP effects provide clear evidence for the distinctive semantic
      representations of these word categories by showing that the activation of a
      name's meaning is mediated by a single connection between identity-specific
      information and person identity, whereas multiple connections exist between nouns
      and their meanings. 

PMID- 25575757
TI  - Toll-like receptor 4 is involved in renoprotective effect of ischemic
      postconditioning after renal ischemia/reperfusion injury in rats.
AB  - OBJECTIVE: To investigate whether the protective effects of ischemic
      postconditioning (IPoC) are associated with the modulation of toll-like receptor
      4 (TLR4) expression. METHODS: We subjected Wistar rats to 45 minutes of ischemia
      followed by reperfusion at 24 hours. Before reperfusion, rats were treated with 6
      cycles of 10 seconds of reperfusion followed by 10 seconds of ischemia. Blood
      samples were collected for the detection of blood urea nitrogen and creatinine
      levels. Histologic examinations were evaluated, and immunohistochemistry was also
      performed for localization of TLR4. The expression of TNF-alpha, IL-1beta, IL-6,
      MCP-1, and TLR4 were studied by real-time polymerase chain reaction or Western
      blot. RESULTS: The results indicated that blood urea nitrogen and creatinine
      levels increased significantly in the ischemia/reperfusion (I/R) group. Rats
      treated with IPoC showed obviously less renal damage. Immunohistochemistry showed
      that TLR4 was ameliorated by IPoC. Real-time polymerase chain reaction showed
      that IPoC could significantly inhibit the increased messenger ribonucleic acid
      level of TNF-alpha, IL-1beta, IL-6, MCP-1, and TLR4 induced by I/R. Western blot
      indicated that the expression of TLR4 was upregulated in I/R group, but IPoC
      could inhibit this increase. CONCLUSION: These findings indicated that IPoC could
      reduce the expression of TLR4 after renal I/R injury, and the modulation of TLR4
      may play a role in the renoprotective effect of IPoC.

PMID- 25575759
TI  - Method for colorimetric detection of double-stranded nucleic acid using leuco
      triphenylmethane dyes.
AB  - Because loop-mediated isothermal amplification (LAMP) can amplify substantial
      amounts of DNA under isothermal conditions, its applications for simple genetic
      testing have attracted considerable attention. A positive LAMP reaction is
      indicated by the turbidity caused by by-products or by the color change after
      adding a metallochromic indicator to the reaction solution, but these methods
      have certain limitations. Leuco crystal violet (LCV), a colorless dye obtained
      after sodium sulfite treatment of crystal violet (CV), was used as a new
      colorimetric method for detecting LAMP. LCV is reconverted into CV through
      contact with double-stranded DNA (dsDNA). Therefore, the positive reaction of
      LAMP is indicated by color change from colorless to violet. The assay is
      sensitive enough to detect LAMP products, with a detection limit of 7.1 ng/MUl
      for dsDNA. It is also highly selective to dsDNA, and interference with single
      stranded DNA and deoxynucleotide triphosphates (dNTPs) is not observed. LCV
      facilitates direct colorimetric detection of the main product rather than a by
      product of the LAMP reaction; therefore, this method can be used under various
      reaction conditions such as those with added pyrophosphatase in solution. This
      colorimetric LAMP detection method using LCV is useful for point-of-care genetic
      testing given its simplicity.

PMID- 25575758
TI  - Identification of oxidized phospholipids in bronchoalveolar lavage exposed to low
      ozone levels using multivariate analysis.
AB  - Chemical reactions with unsaturated phospholipids in the respiratory tract lining
      fluid have been identified as one of the first important steps in the mechanisms
      mediating environmental ozone toxicity. As a consequence of these reactions,
      complex mixtures of oxidized lipids are generated in the presence of mixtures of
      non-oxidized naturally occurring phospholipid molecular species, which challenge
      methods of analysis. Untargeted mass spectrometry and statistical methods were
      employed to approach these complex spectra. Human bronchoalveolar lavage (BAL)
      was exposed to low levels of ozone, and samples with and without derivatization
      of aldehydes were analyzed by liquid chromatography electrospray ionization
      tandem mass spectrometry. Data processing was carried out using principal
      component analysis (PCA). Resulting PCA scores plots indicated an ozone dose
      dependent increase, with apparent separation between BAL samples exposed to 60
      ppb ozone and non-exposed BAL samples as well as a clear separation between
      ozonized samples before and after derivatization. Corresponding loadings plots
      revealed that more than 30 phosphatidylcholine (PC) species decreased due to
      ozonation. A total of 13 PC and 6 phosphatidylglycerol oxidation products were
      identified, with the majority being structurally characterized as chain-shortened
      aldehyde products. This method exemplifies an approach for comprehensive
      detection of low-abundance, yet important, components in complex lipid samples.

PMID- 25575760
TI  - Assembling long heteroduplexes by asymmetric polymerase chain reaction and
      annealing the resulting single-stranded DNAs.
AB  - We developed an effective protocol for generating high-purity heteroduplexes via
      annealing single-stranded DNAs (ssDNAs) derived from plasmid DNA by asymmetric
      polymerase chain reaction (A-PCR). With the addition of dimethyl sulfoxide, a one
      step A-PCR procedure can generate ssDNAs stably at a range of reaction
      temperatures. Several annealing buffers can anneal two ssDNAs into heteroduplexes
      effectively. We further developed a simple strategy to create d(GATC)
      hemimethylated heteroduplexes by annealing fully methylated homoduplexes in the
      presence of excessive unmethylated ssDNAs. The constructed heteroduplexes have
      been well tested as substrates for mismatch repair in Escherichia coli and, thus,
      can be used in various biotechnology applications.

PMID- 25575761
TI  - Enzymatic synthesis of phytosterol esters catalyzed by Candida rugosa lipase in
      water-in-[Bmim]PF6 microemulsion.
AB  - A water-in-ionic liquid microemulsion ([Bmim]PF6/Tween20/H2O) was applied as
      reusable reaction medium to esterify phytosterols with fatty acid by Candida
      rugosa lipase (CRL) successfully. Two kinds of commercial CRLs, AY30 and AYS
      which cannot effectively catalyze esterification in conventional reaction system
      were found effective in the microemulsion system. Effects of reaction parameters
      on esterification were investigated; results showed that the conversion rate of
      87.9 and 95.1 % was obtained in 24 and 48 h of reaction, respectively, under the
      optimized condition: the molar ratio of water to Tween 20 (w 0 value) at 5.4,
      Tween 20 at a concentration of 305 mM, 50  degrees C,pH 7.4, 10 % of enzyme
      loading (w/w, with respect to total reactants), and phytosterols/lauric acid
      molar ratio of 1:2. Moreover, by using n-hexane as the extraction agent, the
      lipase-encapsulated microemulsion could be reused at least seven times (>168 h)
      without significant changes in the conversion rate, while achieving a purpose of
      simple separation and purification. 

PMID- 25575762
TI  - A novel procedure for purification of uridine 5'-monophosphate based on
      adsorption methodology using a hyper-cross-linked resin.
AB  - The conventional ion exchange process used for recovery of uridine 5'
      monophosphate (UMP) from the enzymatic hydrolysate of RNA is environmentally
      harmful and cost intensive. In this work, an innovative benign process, which
      comprises adsorption technology and use of a hyper-cross-linked resin as a
      stationary phase is proposed. The adsorption properties of this kind of resin in
      terms of adsorption equilibrium as well as kinetics were evaluated. The
      influences of the operating conditions, i.e., initial UMP concentration, feed
      flow rate, and bed height on the breakthrough curves of UMP in the fixed bed
      system were investigated. Subsequently, a chromatographic column model was
      established and validated for the prediction of the experimentally attained
      breakthrough curves of UMP and the main impurity component (phosphate ion) with a
      real enzymatic hydrolysate of RNA as a feed mixture. At the end of this paper,
      the crystallization of UMP was carried out. The purity of the final product
      (uridine 5'-monophosphate disodium, UMPNa2) of over 99.5 % was obtained. 

PMID- 25575763
TI  - A novel anaerobic two-phase system for biohydrogen production and in situ
      extraction of organic acid byproducts.
AB  - Owing to CO2-free emission, hydrogen is considered as a potential green
      alternative of fossil fuels. Water is the major emission of hydrogen combustion
      process and gravimetric energy density of hydrogen is nearly three times more
      than that of gasoline and diesel fuel. Biological hydrogen production, therefore,
      has commercial significance; especially, when it is produced from low-cost
      industrial waste-based feedstock. Light independent anaerobic fermentation is
      simple and mostly studied method of biohydrogen production. During hydrogen
      production by this method, a range of organic acid byproducts are produced.
      Accumulation of these byproducts is inhibitory for hydrogen production as it may
      result in process termination due to sharp decrease in medium pH or by possible
      metabolic shift. For the first time, therefore, a two-phase anaerobic bioreactor
      system has been reported for biohydrogen production which involves in situ
      extraction of different organic acids. Among different solvents, based on
      biocompatibility oleyl alcohol has been chosen as the organic phase of the two
      phase system. An organic:aqueous phase ratio of 1:50 has been found to be optimum
      for hydrogen production. The strategy was capable of increasing the hydrogen
      production from 1.48 to 11.65 mmol/L-medium.

PMID- 25575764
TI  - A randomized phase II study of combination therapy with S-1, oral leucovorin, and
      oxaliplatin (SOL) and mFOLFOX6 in patients with previously untreated metastatic
      colorectal cancer.
AB  - PURPOSE: Biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV)
      enhances antitumor activity. LV is thus often added to 5-FU-based regimens for
      the treatment of metastatic colorectal cancer (mCRC). A combination of S-1,
      oxaliplatin, and LV (SOL) was shown to be feasible, effective, and safe in a
      previous phase I trial. We therefore conducted a randomized phase II trial to
      evaluate efficacy and safety of SOL compared with mFOLFOX6. METHODS: Patients
      with mCRC and no prior chemotherapy were randomly assigned to receive either SOL
      or mFOLFOX6. SOL consisted of S-1 (40-60 mg bid) plus oral LV (25 mg bid) for 1
      week and oxaliplatin (85 mg/m(2)) on day 1, repeated every 2 weeks. RESULTS:
      Among 107 patients enrolled from July 2008 through July 2009, 105 (56 in the SOL
      group and 49 in the mFOLFOX6 group) were eligible and evaluated. The median
      progression-free survival was 9.6 months in the SOL group and 6.9 months in the
      mFOLFOX6 group [hazard ratio (HR) 0.83, 95 % confidence interval (CI) 0.49-1.40].
      The median overall survival was 29.9 and 25.9 months, respectively (HR 0.91, 95 %
      CI 0.55-1.49). The response rate was 55 % in both groups. Grade 3 or 4 adverse
      drug reactions were neutropenia (20 % with SOL vs 41 % with mFOLFOX6), sensory
      neuropathy (20 vs 2.0 %), anorexia (13 vs 7.8 %), fatigue (11 vs 5.9 %), and
      diarrhea (11 vs 3.9 %). CONCLUSIONS: SOL demonstrated promising efficacy and
      acceptable toxicity as first-line chemotherapy for mCRC. Further studies of SOL
      combined with molecular target agents are warranted.

PMID- 25575765
TI  - End of the road for a dysfunctional end organ: laparoscopic gastrectomy for
      refractory gastroparesis.
AB  - INTRODUCTION: Gastroparesis is a functional disorder resulting in debilitating
      nausea, esophageal reflux, and abdominal pain and is frequently refractory to
      medical treatment. Therapies such as pyloroplasty and neurostimulators can
      improve symptoms. When medical and surgical treatments fail, palliative
      gastrectomy is an option. We examined outcomes after gastrectomy for
      postoperative, diabetic, and idiopathic gastroparesis. METHODS: A prospective
      database was queried for gastrectomies performed for gastroparesis from 1999 to
      2013. Primary outcomes were improvements in pre- versus postoperative symptoms at
      last follow-up, measured on a five-point scale. Secondary outcome was operative
      morbidity. RESULTS: Thirty-five patients underwent laparoscopic total or near
      total gastrectomies for postoperative (43 %), diabetic (34 %), or idiopathic (23
      %) gastroparesis. Antiemetics and prokinetics afforded minimal relief for one
      third of patients. There were no mortalities. Six patients suffered a leak, all
      treated with surgical reintervention. With a median follow-up of 6 months, nausea
      improved or resolved in 69 %. Chronic abdominal pain improved or resolved in 70
      %. Belching and bloating resolved for 79 and 89 %, respectively (p < 0.01).
      CONCLUSIONS: Regardless of etiology, medically refractory gastroparesis can be a
      devastating disease. Near-total gastrectomy can ameliorate or relieve nausea,
      belching, and bloating. Chronic abdominal pain commonly resolved or improved with
      resection. Despite attendant morbidity, gastrectomy can effectively palliate
      symptoms of gastroparesis.

PMID- 25575766
TI  - Ezetimibe ameliorates atherogenic lipids profiles, insulin resistance and
      hepatocyte growth factor in obese patients with hypercholesterolemia.
AB  - BACKGROUND: Ezetimibe ameliorates serum low-density lipoprotein cholesterol (LDL
      c) and it has been approved for the treatment of hypercholesterolemia. However,
      the effects of ezetimibe on specific biomarkers have not been fully clarified in
      obese Japanese patients. METHODS: A total of 101 patients (47 males and 54
      females) were registered in this study during 2011 and 2012. All patients were
      over 20 years old, were obese [body mass index (BMI) >= 25 kg/m(2)] and had
      hypercholesterolemia (LDL-c >= 120 mg/dl). After excluding 10 subjects (7 who
      dropped out and 3 with missing data), 91 patients (39 males and 52 females) were
      analyzed. They were treated with 10 mg ezetimibe once a day for 24 weeks and were
      evaluated at 12 and 24 weeks. RESULTS: Following 12 weeks of ezetimibe therapy,
      BMI (p < 0.001), waist circumference (p < 0.001), total cholesterol (p < 0.001),
      LDL-c (p < 0.001), non high-density lipoprotein cholesterol [HDL-c] (p < 0.001),
      triglycerides (p < 0.05) and remnant-like particle cholesterol (RLP-c; p < 0.001)
      were significantly decreased. Following 24 weeks of ezetimibe therapy, BMI (p <
      0.05), waist circumference (p < 0.001), total cholesterol (p < 0.001), LDL-c (p <
      0.001), non HDL-c (p < 0.001), triglycerides (p < 0.05), RLP-c (p < 0.001),
      insulin (p < 0.05) and hepatocyte growth factor (HGF; p < 0.05) were
      significantly decreased. In contrast, HDL-c (p < 0.001) was significantly
      increased. CONCLUSIONS: Ezetimibe ameliorated not only atherogenic lipid profiles
      but also anthropometric factors, insulin resistance and biomarkers such as HGF.
      Ezetimibe may have pleiotropic effects on obese patients with
      hypercholesterolemia.

PMID- 25575767
TI  - MicroRNA-15a down-regulation is associated with adverse prognosis in human
      glioma.
AB  - OBJECTIVE: The aim of this study was to investigate whether miR-15a has
      prognostic relevance in human gliomas. METHODS: The expression levels of miR-15a
      were analyzed in glioma surgical resection tissues by microarray and quantitative
      real-time PCR. Survival analysis by the Kaplan-Meier method was performed to
      assess prognostic significance. RESULTS: Downregulation of miR-15a was detected
      in most primary gliomas, which was confirmed by qRT-PCR analysis. Additionally,
      the down-regulation of miR-15a was significantly associated with the WHO grade (P
      = 0.003), the low KPS (P = 0.027), time to recurrence (P = 0.044) and the poor OS
      (P = 0.046). Using Kaplan-Meier analysis, a comparison of survival curves of low
      versus high expresser of miR-15a revealed a highly significant difference in OS
      (P = 0.001) and DFS (P = 0.006), which suggested that low expression of miR-15a
      is associated with a worse prognosis. Multivariate analyses showed that miR-15a
      expression was independent risk factors predicting OS [Hazard ratio (HR), 7.52;
      95 % confidence interval (CI), 2.63-21.47; P = 0.002] and DFS [HR, 11.56; 95 %
      CI, 5.17-25.96; P < 0.001] in glioma. CONCLUSIONS: These findings indicated for
      the first time that the expression of miR-15a is significantly correlated with
      prognosis in glioma patients, suggesting that the miR-15a may serve as
      independent prognostic marker.

PMID- 25575768
TI  - Misuse of stimulant medication among college students: a comprehensive review and
      meta-analysis.
AB  - The misuse of stimulant medication among college students is a prevalent and
      growing problem. The purpose of this review and meta-analysis is to summarize the
      current research on rates and demographic and psychosocial correlates of
      stimulant medication misuse among college students, to provide methodological
      guidance and other ideas for future research, and to provide some preliminary
      suggestions for preventing and reducing misuse on college campuses. Random
      effects meta-analysis found that the rate of stimulant medication misuse among
      college students was estimated at 17 % (95 % CI [0.13, 0.23], p < .001) and
      identified several psychological variables that differentiated misusers and
      nonusers, including symptoms of attention-deficit/hyperactivity disorder,
      problems associated with alcohol use, and marijuana use. A qualitative review of
      the literature also revealed that Greek organization membership, academic
      performance, and other substance use were associated with misuse. Students are
      misusing primarily for academic reasons, and the most common source for obtaining
      stimulant medication is peers with prescriptions. Interpretation of findings is
      complicated by the lack of a standard misuse definition as well as validated
      tools for measuring stimulant misuse. The relation between stimulant medication
      misuse and extra curricular participation, academic outcomes, depression, and
      eating disorders requires further investigation, as do the reasons why students
      divert or misuse and whether policies on college campuses contribute to the high
      rates of misuse among students. Future research should also work to develop and
      implement effective prevention strategies for reducing the diversion and misuse
      of stimulant medication on college campuses. 

PMID- 25575769
TI  - Risk factors for periprosthetic joint infection after total joint arthroplasty: a
      systematic review and meta-analysis.
AB  - Many of the mooted risk factors associated with periprosthetic joint infection
      (PJI) after total joint arthroplasty (TJA) remain controversial and are not well
      characterized. Online and manual searches were performed using Medline, Embase,
      Chinese National Knowledge Infrastructure and the Cochrane Central Database from
      January 1980 to March 2014). For inclusion, studies had to meet the quality
      assessment criteria of the CONSORT statement, and be concerned with evaluation of
      risk factors for PJI after TJA. Two reviewers extracted the relevant data
      independently and any disagreements were resolved by consensus. Fourteen studies
      were included in this meta-analysis. The following significant risk factors for
      PJI were identified: body mass index (both continuous and dichotomous variables);
      diabetes mellitus; corticosteroid therapy; hypoalbuminaemia; history of
      rheumatoid arthritis; blood transfusion; presence of a wound drain; wound
      dehiscence; superficial surgical site infection; coagulopathy; malignancy,
      immunodepression; National Nosocomial Infections Surveillance Score >=2; other
      nosocomial infection; prolonged operative time; and previous surgery. Factors
      that were not significantly associated with PJI were: cirrhosis; hypothyroidism;
      urinary tract infection; illicit drug abuse; alcohol abuse;
      hypercholesterolaemia; hypertension, ischaemic heart disease; peptic ulcer
      disease; hemiplegia or paraplegia; dementia; and operation performed by a staff
      surgeon (vs a trainee). Strategies to prevent PJI after TJA should focus, in
      particular, on those patients at greatest risk of infection according to their
      individual risk factors. 

PMID- 25575770
TI  - Clostridium difficile infection targets.

PMID- 25575781
TI  - Low concentrations of cylindrospermopsin induce increases of reactive oxygen
      species levels, metabolism and proliferation in human hepatoma cells (HepG2).
AB  - Human hepatoma cells (HepG2) were exposed to purified cylindrospermopsin (CYN), a
      potent toxicant for eukaryotic cells produced by several cyanobacteria. CYN was
      not toxic at concentrations up to 10 MUgl(-1), leading to increased viability and
      metabolism in cells cultured with 10% fetal bovine serum (FBS). Reduction of FBS
      concentration to 2% and induction of cytochrome P450 (CYP) isoforms were
      performed in order to make xenobiotic-metabolizing capacity of HepG2 cells
      closest to that of 'normal' cells. HepG2 cells proliferated less after CYPs
      induction, and this induction has lead to similar results of non-induced cells,
      except for few individual parameters such lipid peroxidation. Foremost, low
      concentrations of CYN (below or equal 10 MUgl(-1)) have induced HepG2 cells
      proliferation and metabolism increase, which was not expected.

PMID- 25575782
TI  - Toxicity of copper oxide nanoparticles in lung epithelial cells exposed at the
      air-liquid interface compared with in vivo assessment.
AB  - The toxicity of spark-generated copper oxide nanoparticles (CuONPs) was evaluated
      in human bronchial epithelial cells (HBEC) and lung adenocarcinoma cells (A549
      cells) using an in vitro air-liquid interface (ALI) exposure system. Dose
      response results were compared to in vivo inhalation and instillation studies of
      CuONPs. Cells were exposed to filtered, particle-free clean air (controls) or
      spark-generated CuONPs. The number median diameter, geometric standard deviation
      and total number concentration of CuONPs were 9.2 nm, 1.48 and
      2.27*10(7)particles/cm(3), respectively. Outcome measures included cell
      viability, cytotoxicity, oxidative stress and proinflammatory chemokine
      production. Exposure to clean air (2 or 4h) did not induce toxicity in HBEC or
      A549 cells. Compared with controls, CuONP exposures significantly reduced cell
      viability, increased lactate dehydrogenase (LDH) release and elevated levels of
      reactive oxygen species (ROS) and IL-8 in a dose-dependent manner. A549 cells
      were significantly more susceptible to CuONP effects than HBEC. Antioxidant
      treatment reduced CuONP-induced cytotoxicity. When dose was expressed per area of
      exposed epithelium there was good agreement of toxicity measures with murine in
      vivo studies. This demonstrates that in vitro ALI studies can provide meaningful
      data on nanotoxicity of metal oxides.

PMID- 25575783
TI  - New labeled derivatives of the neuroprotective peptide colivelin: synthesis,
      characterization, and first in vitro and in vivo applications.
AB  - Colivelin (CL), first reported in 2005, is the most potent member of the humanin
      family of neuroprotective peptides with in vitro and in vivo rescuing action
      against insults associated with Alzheimer's disease (AD). The objective of the
      present work is the design, synthesis and characterization of specific CL
      derivatives that can be used as molecular probes in the investigation of the
      unknown mechanism of CL action. Within this framework, three CL derivatives
      bearing suitable tags, i.e., the fluorescent moiety FITC, the streptavidin
      counterpart biotinyl-group, and the (99m)Tc-radiometal chelating unit dimethylGly
      Ser-Cys, were developed and subsequently applied in biological evaluation
      experiments. Specifically, the FITC-labeled derivative of CL was used in confocal
      microscopy, where specific binding at the periphery of F11 cells was observed;
      the biotin-labeled derivative of CL was used in an in-house developed ELISA-type
      assay, where specific and concentration-dependent binding with the beta-amyloid
      peptide of AD was shown; finally, the (99m)Tc-radiolabeled derivative of CL was
      used in in vivo biodistribution studies in healthy Swiss Albino mice, where 0.58%
      of the radioactivity administered was measured in the mouse brain 2min after
      injection. The above first successful applications of the CL probes demonstrate
      their potential to contribute in the field of neuroprotective peptides. 

PMID- 25575784
TI  - Molecular characterization of cbfbeta gene and identification of new
      transcription variants: implications for function.
AB  - The CBFbeta gene encodes a transcription factor that, in combination with
      CBFalpha (also called Runx, runt-related transcription factor) regulates
      expression of several target genes. CBFbeta interacts with all Runx family
      members, such as RUNX2, a regulator of bone-related gene transcription that
      contains a conserved DNA-binding domain. CBFbeta stimulates DNA binding of the
      Runt domain, and is essential for most of the known functions of RUNX2. A
      comparative analysis of the zebrafish cbfbeta gene and protein, and of its
      orthologous identified homologous proteins in different species indicates a
      highly conserved function. We cloned eleven zebrafish cbfbeta gene transcripts,
      one resulting in the known Cbfbeta protein (with 187 aa), and three additional
      variants resulting from skipping exon 5a (resulting in a protein with 174 aa) or
      exon 5b (resulting in a protein with 201 aa), both observed for the first time in
      zebrafish, and a completely novel isoform containing both exon 5a and 5b
      (resulting in a protein with 188 aa). Functional analysis of these isoforms
      provides insight into their role in regulating gene transcription. From the other
      variants two are premature termination Cbfbeta forms, while the others show in
      frame exon-skipping causing changes in the Cbfbeta domain that may affect its
      function. 

PMID- 25575785
TI  - Endurance training prevents TWEAK but not myostatin-mediated cardiac remodelling
      in cancer cachexia.
AB  - Strategies to prevent tumour burden-induced cardiac remodelling that might
      progress to heart failure are necessary to improve patients' health outcomes and
      tolerability to cancer therapies. Exercise has been suggested as a measure to
      prevent cardiac damage; however, its effectiveness on regulating cardiac
      remodelling secondary to cancer was never addressed. Using an animal model of
      mammary tumorigenesis, we studied the impact of 35weeks of endurance training on
      heart, focusing on the signalling pathways modulated by pro-inflammatory and
      wasting cytokines. The cardiac fibrosis and myofiber disorganization induced by
      tumour burden was paralleled by the increase of myostatin and TWEAK with the
      activation of signalling pathways involving Smad-3, NF-kappaB, TRAF-6 and atrogin
      1. The activation of Akt/mTOR was observed in heart from rats with tumours, for
      which contributed the extracellular matrix. Endurance training prevented the
      increase of serum and cardiac TWEAK promoted by cancer, as well as the activation
      of NF-kappaB, TRAF6, atrogin-1 and p70S6K in heart. Data highlight the impact of
      exercise in the modulation of signalling pathways activated by wasting cytokines
      and the resulting outcomes on heart adaptation. Future studies focused on the
      cellular pathways underlying cardiac remodelling will assist in the development
      of exercise programs targeting cancer-related cardiac alterations. 

PMID- 25575786
TI  - Cellular localization of beta-carotene 15,15' oxygenase-1 (BCO1) and beta
      carotene 9',10' oxygenase-2 (BCO2) in rat liver and intestine.
AB  - The intestine and liver are crucial organs for vitamin A uptake and storage.
      Liver accounts for 70% of total body retinoid stores. Vitamin A deficiency (VAD)
      is a major micronutrient deficiency around the world. The provitamin A
      carotenoid, beta-carotene, is a significant source of vitamin A in the diet. beta
      Carotene 15,15' oxygenase-1 (BCO1) and beta-carotene 9',10' oxygenase-2 (BCO2)
      are the two known carotenoid cleavage enzymes in humans. BCO1 and BCO2 are highly
      expressed in liver and intestine. Hepatocytes and hepatic stellate cells are two
      main cell types involved in the hepatic metabolism of retinoids. Stellate-like
      cells in the intestine also show ability to store vitamin A. Liver is also known
      to accumulate carotenoids, however, their uptake, retention and metabolism in
      specific liver and intestinal cell types is still unknown. Hence, we studied the
      cellular and subcellular expression and localization of BCO1 and BCO2 proteins in
      rat liver and intestine. We demonstrate that both BCO1 and BCO2 proteins are
      localized in hepatocytes and mucosal epithelium. We also show that BCO1 is also
      highly expressed in hepatic stellate cells (HSC) and portal endothelial cells in
      liver. At the subcellular level in liver, BCO1 is found in cytosol, while BCO2 is
      found in mitochondria. In intestine, immunohistochemistry showed strong BCO1
      immunoreactivity in the duodenum, particularly in Brunner's glands. Both BCO1 and
      BCO2 showed diffuse presence along epithelia with strong immunoreactivity in
      endothelial cells and in certain epithelial cells which warrant further
      investigation as possible intestinal retinoid storage cells.

PMID- 25575787
TI  - Long-term outcomes in heart transplantation using donors with a history of past
      and present cocaine use.
AB  - OBJECTIVES: Organ donors with a history of cocaine use are thought to be less
      favourable for orthotopic heart transplantation (OHT). This study examined long
      term survival in OHT using donors with a history of cocaine use. METHODS: The
      United Network for Organ Sharing (UNOS) database was examined for primary, adult
      heart transplants from 2000 to 2010. Cox proportional hazards analysis using
      covariates associated with mortality was used to examine survival. RESULTS: There
      were 19 636 total OHTs with 2274 (11.6%) using donors with a history of dependent
      cocaine use (DCU). Of these, 1008 (44.3%) donors were current cocaine users.
      Recipients of DCU were more likely to be male (79.0 vs 75.7%, P < 0.001), more
      likely diabetic (16.5 vs 14.8%, P = 0.003) and were less likely to be sex
      mismatched (23.0 vs 28.6%, P < 0.001). DCU donors were older (32.5 vs 31.4 years,
      P < 0.001), more likely male (79.7 vs 69.8%, P < 0.001) and had higher ischaemic
      times (3.27 vs 3.20 h, P = 0.001). On multivariate analysis, DCU was not
      associated with mortality [hazard ratio (HR): 0.95, 95% CI: 0.87-1.03, P = 0.22].
      Variables associated with mortality included recipient body mass index, sex
      mismatch, race mismatch, black race, ischaemic time, recipient creatinine, donor
      age, donor smoking history and mechanical ventilation or extracorporeal membrane
      oxygen as a bridge to transplantation. On subset analysis, CCU was not associated
      with mortality (HR: 0.97, 95% CI: 0.89-1.05, P = 0.42). On Kaplan-Meier analysis,
      median survival was not different when comparing current (3890.0 days), past
      (3,889.0 days) and non-cocaine using donors (4165.0 days); P = 0.54. CONCLUSIONS:
      Use of carefully selected donors with a history of past and current cocaine use
      does not result in worse outcomes.

PMID- 25575788
TI  - Use of self-expanding venous cannula in tricuspid reoperation.
AB  - Significant tricuspid regurgitation requiring surgical correction is associated
      with poor survival in patients undergoing tricuspid valve reoperations. Right
      chamber dilatation increases the risk of injury during resternotomy. The novel
      technique of peripheral cannulation using an expandable venous cannula for
      cardiopulmonary bypass can help to reduce the risk of complications and
      associated morbidity, thus enhancing the short-term outcomes. 

PMID- 25575789
TI  - Complications and surgical conversion after total aortic repair using
      endovascular repair in patients with Marfan syndrome.
AB  - We report a case of a Marfan syndrome patient who developed a complicated
      clinical course after total aortic repair using a hybrid technique. After hybrid
      total aortic repair, this patient was required to undergo open thoracic and
      thoracoabdominal aortic repair due to impending rupture of the aorta. Moreover,
      the abdominal aortic graft was rereplaced due to debranching graft occlusion of
      the coeliac artery and the left renal artery. 

PMID- 25575790
TI  - Ultrahigh-performance liquid chromatography-ion trap mass spectrometry
      characterization of the steroidal saponins of Dioscorea panthaica Prain et
      Burkill and its application for accelerating the isolation and structural
      elucidation of steroidal saponins.
AB  - Dioscorea panthaica is a traditional Chinese medicinal herb used in the treatment
      of various physiological conditions, including cardiovascular disease,
      gastropathy and hypertension. Steroidal saponins (SS) are the main active
      ingredients of this herb and have effects on myocardial ischemia and cancer. The
      phytochemical evaluation of SS is both time-consuming and laborious, and the
      isolation and structural determination steps can be especially demanding. For
      this reason, the development of new methods to accelerate the processes involved
      in the identification, isolation and structural elucidation of SS is highly
      desirable. In this study, a new ultrahigh performance liquid chromatography-ion
      trap mass spectrometry (UHPLC-IT/MS(n)) method has been developed for the
      identification of the SS in D. panthaica Prain et Burkill. Notably, the current
      method can distinguish between spirostanol and furostanol-type compounds based on
      the fragmentation patterns observed by electrospray ionization-ion trap mass
      spectrometry (ESI-IT/MS(n)) analysis. UHPLC-IT/MS(n) was used to conduct a
      detailed investigation of the number, structural class and order of the sugar
      moieties in the sugar chains of the SS present in D. panthaica. The established
      fragmentation features were used to analyze the compounds found in the 65%
      ethanol fraction of the water extracts of D. panthaica. Twenty-three SS were
      identified, including 11 potential new compounds and six groups of isomers. Two
      of these newly identified SS were selected as representative examples, and their
      chemical structures were confirmed by (1)H and (13)C NMR analyses. This newly
      developed UHPLC-IT/MS(n) method therefore allowed for the efficient
      identification, isolation and structural determination of the SS in D. panthaica.

PMID- 25575791
TI  - Spotlight on cellular lipid binding proteins.

PMID- 25575793
TI  - Ca(2+) influx mediates the TRPV4-NO pathway in neuropathic hyperalgesia following
      chronic compression of the dorsal root ganglion.
AB  - Chronic compression of the dorsal root ganglion (DRG) (CCD) in rats is a typical
      model of neuropathic pain. TRPV4 contributed to mechanical allodynia induced by
      the CCD model. Our previous study demonstrated that TRPV4 enhances neuropathic
      hyperalgesia through a NO-cGMP-PKG cascade. However, the underlying mechanism(s)
      is still largely unknown. Therefore, the aim of the present study was to test
      whether TRPV4-mediated Ca(2+) influx is involved in the TRPV4-NO pathway.
      Regulation of intracellular calcium concentration by intrathecal injection of
      TRPV4-targeted siRNA significantly decreased the behavioural hyperalgesia, NF
      kappaB activity, and NO content in CCD rats. Intraperitoneal (i.p.) injection of
      mibefradil significantly induced dose-dependent increases in the paw withdrawal
      latency (PWL) and mechanical withdrawal thresholds (MWT), as well as decreases in
      NF-kappaB activity and NO content in DRG of CCD rats. Moreover, pre-treatment
      with 4alpha-PDD attenuated the suppressive effects of mibefradil on CCD-induced
      neuropathic hyperalgesia, NF-kappaB activity, and NO production. The data showed
      that TRPV4-mediated Ca(2+) influx might be engaged in the TRPV4-NO pathway in
      neuropathic hyperalgesia in the CCD model. 

PMID- 25575792
TI  - Chromoblastomycosis due to Fonsecaea monophora in a man with nephritic syndrome.
AB  - Chromoblastomycosis is a chronic subcutaneous mycosis caused by dematiaceous
      fungi. Fonsecaea monophora, a new species segregated from F. pedrosoi, may be the
      most prevalent pathogen of chromoblastomycosis in southern China. Herein, we
      report a rare case of chromoblastomycosis in a man with nephritic syndrome. He
      presented with an asymptomatic red plaque on the back of his left wrist that had
      appeared and enlarged over a period of 1.5 years, without any prior trauma. He
      was initially diagnosed with sporotrichosis. However, he did not respond to a 6
      month course of potassium iodide treatment. The lesion slowly enlarged and became
      verrucous instead. Concurrently, a similar maculopapule appeared on his left
      forearm. Histopathological examination of a biopsy specimen indicated the
      presence of sclerotic bodies in the dermis. The fungus was identified as
      Fonsecaea spp. based on the results of a slide culture; in addition, the agent
      was confirmed to be F. monophora by using molecular methods. The patient
      demonstrated marked improvement after receiving appropriate antifungal therapy
      for 3 months. To our knowledge, this is the first case of chromoblastomycosis
      caused by F. monophora in an immunosuppressed patient. The identification of the
      agent by molecular techniques is important for epidemiological purposes. Thus, we
      believe that combination therapy with itraconazole and terbinafine would be a
      suitable option for infections caused by F. monophora.

PMID- 25575794
TI  - Magnolol derivative 002C-3 protects brain against ischemia-reperfusion injury via
      inhibiting apoptosis and autophagy.
AB  - Neuroprotective agents can rescue ischemic penumbra in cerebral ischemia.
      However, the clinically effective neuroprotective agents for cerebral ischemic
      injury remain deficient in clinic so far. This study was undertaken to
      investigate the brain protective effect of 002C-3 and its potential mechanisms in
      rats, and its preliminary toxicity in mice. A transient middle cerebral artery
      occlusion (tMCAO) model in rats was used to evaluate its effect and mechanism, a
      dose limited experiment was used to evaluate its preliminary toxicity. 10
      50MUg/kg of 002C-3 (single iv bolus after reperfusion) significantly reduced
      neurological scores, infarct volumes and brain water contents, and the effect was
      more potent than that of magnolol under the same mole dose; 50MUg/kg of 002C-3
      significantly decreased the number of TUNEL-positive cells, reduced the activity
      of caspase-3, and lowered the autophagy-related proteins LC3-II and Beclin-1
      level in I-R cerebral tissue. At 1000 times' dose of high effective dose (ip)
      002C-3 failed to show evident toxicity in mice, and the mean body weight of mice
      treated with 002C-3 was almost the same as that of the vehicle control, but
      magnolol caused evident toxicity and death. In conclusion, 002C-3 has significant
      protective effect against cerebral ischemia-reperfusion injury; the effect is
      more potent than magnolol; this effect is maybe associated with its inhibition of
      both apoptosis and autophagy; its toxicity is greatly reduced compared to
      magnolol. These results provided data for its further research and development. 

PMID- 25575795
TI  - Activation of cannabinoid receptor 1 inhibits increased bladder activity induced
      by nerve growth factor.
AB  - Nerve growth factor (NGF) is an important mediator of inflammatory pain, in part
      by sensitizing afferent nerve fibers, and expression of NGF is increased during
      bladder inflammation. We investigated whether intravesical instillation of the
      selective cannabinoid receptor 1 (CB1) agonist arachidonyl-2'-chloroethylamide
      (ACEA) affects NGF-induced increased bladder activity in female C57BL/6J wild
      type (WT) mice. We also examined the effects of intravesical NGF in female fatty
      acid amide hydrolase knock-out (FAAH KO) mice. We found that CB1 and tyrosine
      kinase A (trkA, the high-affinity NGF receptor) were present in L6 dorsal root
      ganglion (DRG) afferent neurons and in bladders of both genotypes. Intravesical
      NGF increased bladder activity that was inhibited by intravesical ACEA in WT
      mice. The inhibitory effects of ACEA were reversed by the selective CB1
      antagonist AM 251. Intravesical NGF failed to affect bladder activity in FAAH KO
      mice, and treatment with AM251, restored the stimulatory effects of NGF on the
      bladder in FAAH KO mice. These results indicate that activation of CB1 inhibits
      increased bladder activity induced by NGF. 

PMID- 25575796
TI  - Administration of a PTEN inhibitor BPV(pic) attenuates early brain injury via
      modulating AMPA receptor subunits after subarachnoid hemorrhage in rats.
AB  - The aim of this study was to investigate whether the phosphatase and tensin
      homolog deleted on chromosome ten (PTEN) inhibitor dipotassium bisperoxo(pyridine
      2-carboxyl) oxovanadate (BPV(pic)) attenuates early brain injury by modulating
      alpha-amino-3-hydroxy-5-methyl-4-isoxa-zolep-propionate (AMPA) receptor subunits
      after subarachnoid hemorrhage (SAH). A standard intravascular perforation model
      was used to produce the experimental SAH in Sprague-Dawley rats. BPV(pic)
      treatment (0.2mg/kg) was evaluated for effects on neurological score, brain water
      content, Evans blue extravasation, hippocampal neuronal death and AMPA receptor
      subunits alterations after SAH. We found that BPV(pic) is effective in
      attenuating BBB disruption, lowering edema, reducing hippocampal neural death and
      improving neurological outcomes. In addition, the AMPA receptor subunit GluR1
      protein expression at cytomembrane was downregulated, whereas the expression of
      GluR2 and GluR3 was upregulated after BPV(pic) treatment. Our results suggest
      that PTEN inhibited by BPV(pic) plays a neuroprotective role in SAH
      pathophysiology, possibly by alterations in glutamate AMPA receptor subunits. 

PMID- 25575797
TI  - Psychosocial moderators of associations between life events and changes in
      physical activity after leaving high school.
AB  - OBJECTIVES: To examine 1) associations between life events and changes in leisure
      time physical activity (LTPA) in school leavers and 2) whether these associations
      are moderated by psychosocial factors. METHODS: Final year students (n=440) from
      high schools in rural Western Australia completed annual telephone interviews on
      three occasions; baseline (T1), one-year follow-up (T2; n=440) and two-year
      follow-up (T3; n=374). LTPA was measured using the Minnesota Leisure-time
      Physical Activity Questionnaire. Life events included moving out of home, working
      full-time and studying full-time. Psychosocial factors included enjoyment, self
      efficacy, outcome expectations, club membership, and support from family and
      friends. Mixed linear regression models examined the effect of life events on
      changes in LTPA from T1 to T2 and T1 to T3. RESULTS: A decline in LTPA across all
      time points was observed. Those who continued full-time education had a smaller
      LTPA decline than those who did not. Those who were not a member of a sporting
      club at T1 had greater LTPA decline if they worked full-time at T2. CONCLUSIONS:
      There is a need for interventions to prevent declines in LTPA among school
      leavers, especially those who do not enter tertiary education. Encouraging
      sporting club membership during high school might be important.

PMID- 25575798
TI  - Sedentary work--associations between five-year changes in occupational sitting
      time and body mass index.
AB  - OBJECTIVE: The aim of this study is to investigate the association between five
      year changes in occupational sitting and body mass index (BMI) in working adults.
      METHODS: We analyzed data from The Danish Work Environment Cohort Study (2005 and
      2010, n=3.482). Data on occupational sitting, weight, height and several
      potential confounders were self-reported. The association between change in
      occupational sitting (hours) (categorized as large decrease <-7.5, moderate
      decrease -7.5 to <-2.5, no change -2.5 to 2.5, moderate increase >2.5 to 7.5 and
      large increase >7.5) and change in BMI was explored by multiple linear regression
      analyses. RESULTS: 43.0% men and 36.1% women had high occupational sitting time
      (>=25h per week) at baseline. 31.8% men and 27.2% women decreased while 30.0% men
      and 33.0% women increased occupational sitting. The proportion of obese (BMI>=30)
      increased almost 3% for both genders. BMI changed 0.13 (CI: 0.06; 0.20,
      p=0.0003), per category of change in occupational sitting in women, but no
      association was found in men. CONCLUSION: In women, there is a positive
      association between five-year changes in occupational sitting and BMI.

PMID- 25575799
TI  - Addressing inequalities in physical activity participation: implications for
      public health policy and practice.
AB  - OBJECTIVE: To investigate the characteristics of those doing no moderate-vigorous
      physical activity (MVPA) (0 days/week), some MVPA (1-4 days/week) and sufficient
      MVPA (>= 5 days/week) to meet the guidelines in order to effectively develop and
      target PA interventions to address inequalities in participation. METHOD: A
      population survey (2010/2011) of 4653 UK adults provided data on PA and socio
      demographic characteristics. An ordered logit model investigated the covariates
      of 1) participating in no PA, 2) participating in some PA, and 3) meeting the PA
      guidelines. Model predictions were derived for stereotypical subgroups to
      highlight important policy and practice implications. RESULTS: Mean age of
      participants was 45 years old (95% CI 44.51, 45.58) and 42% were male.
      Probability forecasting showed that males older than 55 years of age
      (probability=0.20; 95% CI 0.11, 0.28), and both males (probability=0.31; 95% CI
      0.17, 0.45) and females (probability=0.38; 95% CI 0.27, 0.50) who report poor
      health are significantly more likely to do no PA. CONCLUSIONS: Understanding the
      characteristics of those doing no MVPA and some MVPA could help develop
      population-level interventions targeting those most in need. Findings suggest
      that interventions are needed to target older adults, particularly males, and
      those who report poor health.

PMID- 25575800
TI  - Implementation of school based physical activity interventions: a systematic
      review.
AB  - OBJECTIVE: Implementation science is an emerging area in physical activity (PA)
      research. We sought to establish the current state of the evidence related to
      implementation of school-based PA models to explore 1) the relationship between
      implementation and health outcomes, and 2) factors that influence implementation.
      METHODS: We searched 7 electronic databases (1995-2014) and included controlled
      studies of school-based PA programmes for healthy youth (6-18 y) measuring at
      least one physical health-related outcome. For objective 1, studies linked
      implementation level to student-level health outcome(s). For objective 2, studies
      reported factors associated with implementation. RESULTS: There was substantial
      variability in how health outcomes and implementation were assessed. Few studies
      linked implementation and health outcomes (n=15 interventions). Most (11/15)
      reported a positive relationship between implementation and at least one health
      outcome. Implementation factors were reported in 29 interventions. Of 22 unique
      categories, time was the most prevalent influencing factor followed by resource
      availability/quality and supportive school climate. CONCLUSIONS: Implementation
      evaluation supports scale-up of effective school-based PA interventions and thus
      population-level change. Our review serves as a call to action to 1) address the
      link between implementation and outcome within the school-based PA literature and
      2) improve and standardize definitions and measurement of implementation.

PMID- 25575801
TI  - Association between unmet dental needs and school absenteeism because of illness
      or injury among U.S. school children and adolescents aged 6-17 years, 2011-2012.
AB  - BACKGROUND: We assessed the prevalence of dental disease among U.S. children and
      adolescents aged 6-17 years, as well as the impact of unmet dental needs on
      school absenteeism because of illness/injury within the past 12 months. METHODS:
      Data were from the 2011/2012 National Survey of Children's Health (n=65,680).
      Unmet dental need was defined as lack of access to appropriate and timely
      preventive or therapeutic dental healthcare when needed within the past 12
      months. The impact of unmet dental needs on school absenteeism was measured using
      a multivariate generalized linear model with Poisson probability distribution
      (p<0.05). RESULTS: Within the past 12 months, 21.8% (10.8 million) of all U.S.
      children and adolescents aged 6-17 years had "a toothache, decayed teeth, or
      unfilled cavities." Of all U.S. children and adolescents aged 6-17 years, 15.8%
      (7.8 million) reported any unmet dental need (i.e., preventive and/or therapeutic
      dental need) within the past 12 months. The mean number of days of school absence
      because of illness/injury was higher among students with an unmet therapeutic
      dental need in the presence of a dental condition compared to those reporting no
      unmet dental need (beta=0.25; p<0.001). CONCLUSIONS: Enhanced and sustained
      efforts are needed to increase access to dental services among underserved U.S.
      children and adolescents.

PMID- 25575802
TI  - Mean arterial pressure is better at predicting future metabolic syndrome in the
      normotensive elderly: a prospective cohort study in Taiwan.
AB  - OBJECTIVE: To compare four different blood pressure (BP) measurements-systolic BP
      (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)
      in predicting future metabolic syndrome (MetS) among the normotensive elderly
      population, and to estimate the optimal cutoff value of the best single
      measurement for clinical practice. METHODS: A total of 2782 non-medicated
      participants aged >= 60 years were enrolled in a standard health examination
      program in Taiwan from January 2004 to December 2013. Two thirds of the
      participants were randomly designated as the training group (n=1855) and the
      other one third as the validation group (n=927). The mean follow-up time was 3.60
      years for both the training and validation groups. MAP and PP were calculated
      from SBP and DBP. RESULTS: SBP, DBP, and MAP were associated with future MetS,
      whereas PP was not. MAP had the largest hazard ratio in Cox regression (men 1.342
      [95% CI 1.158-1.555] and women 1.348 [95% CI 1.185-1.534] in the training group;
      men 1.640 [95% CI 1.317-2.041] and women 1.485 [95% CI 1.230-1.794] in the
      validation group) and the largest area under the receiver operating
      characteristic curve (men 0.598 +/- 0.021 and women 0.602 +/- 0.021 in the
      training group). Multivariable Cox regression further indicated that a higher MAP
      level was independently associated with the future occurrence of MetS.
      Participants with MAP above the cutoff value (84.0mm Hg for men, 83.3mm Hg for
      women) had a higher cumulative incidence of MetS than did their counterparts
      after four years' follow-up in both the training and validation groups. The
      results derived from the training data could be replicated in the validation
      data, indicating that the results were generalizable across distinct samples.
      CONCLUSIONS: MAP is more accurate than SBP, DBP, and PP in predicting future MetS
      among the normotensive geriatric population. Calculation of MAP is recommended
      when dealing with normotensive patients aged >= 60 years in clinical practice.

PMID- 25575803
TI  - Sex Offender Recidivism Revisited: Review of Recent Meta-analyses on the Effects
      of Sex Offender Treatment.
AB  - The effectiveness of sex offender treatment programs continues to generate
      misinformation and disagreement. Some literature reviews conclude that treatment
      does not reduce recidivism while others suggest that specific types of treatment
      may warrant optimism. The principal purpose of this study is to update the most
      recent meta-analyses of sex offender treatments and to compare the findings with
      an earlier study that reviewed the meta-analytic studies published from 1995 to
      2002. More importantly, this study examines effect sizes across different age
      populations and effect sizes across various sex offender treatments. Results of
      this review of meta-analyses suggest that sex offender treatments can be
      considered as "proven" or at least "promising," while age of participants and
      intervention type may influence the success of treatment for sex offenders. The
      implications of these findings include achieving a broader understanding of
      intervention moderators, applying such interventions to juvenile and adult
      offenders, and outlining future areas of research. 

PMID- 25575805
TI  - Batchwise dyeing of bamboo cellulose fabric with reactive dye using ultrasonic
      energy.
AB  - Bamboo is a regenerated cellulose fiber usually dyed with reactive dyes. This
      paper presents results of the batchwise dyeing of bamboo fabric with reactive
      dyes by ultrasonic (US) and conventional (CN) dyeing methods. The study was
      focused at comparing the two methods for dyeing results, chemicals, temperature
      and time, and effluent quality. Two widely used dyes, CI Reactive Black 5 (bis
      sulphatoethylsulphone) and CI Reactive Red 147 (difluorochloropyrimidine) were
      used in the study. The US dyeing method produced around 5-6% higher color yield
      (K/S) in comparison to the CN dyeing method. A significant savings in terms of
      fixation temperature (10 degrees C) and time (15 min), and amounts of salt (10
      g/L) and alkali (0.5-1% on mass of fiber) was realized. Moreover, the dyeing
      effluent showed considerable reductions in the total dissolved solids content
      (minimum around 29%) and in the chemical oxygen demand (minimum around 13%) for
      the US dyebath in comparison to the CN dyebath. The analysis of colorfastness
      tests demonstrated similar results by US and CN dyeing methods. A microscopic
      examination on the field emission scanning electron microscope revealed that the
      US energy did not alter the surface morphology of the bamboo fibers. It was
      concluded that the US dyeing of bamboo fabric produces better dyeing results and
      is a more economical and environmentally sustainable method as compared to CN
      dyeing method.

PMID- 25575804
TI  - Overview on mechanisms of acetic acid resistance in acetic acid bacteria.
AB  - Acetic acid bacteria (AAB) are a group of gram-negative or gram-variable bacteria
      which possess an obligate aerobic property with oxygen as the terminal electron
      acceptor, meanwhile transform ethanol and sugar to corresponding aldehydes,
      ketones and organic acids. Since the first genus Acetobacter of AAB was
      established in 1898, 16 AAB genera have been recorded so far. As the main
      producer of a world-wide condiment, vinegar, AAB have evolved an elegant adaptive
      system that enables them to survive and produce a high concentration of acetic
      acid. Some researches and reviews focused on mechanisms of acid resistance in
      enteric bacteria and made the mechanisms thoroughly understood, while a few
      investigations did in AAB. As the related technologies with proteome,
      transcriptome and genome were rapidly developed and applied to AAB research, some
      plausible mechanisms conferring acetic acid resistance in some AAB strains have
      been published. In this review, the related mechanisms of AAB against acetic acid
      with acetic acid assimilation, transportation systems, cell morphology and
      membrane compositions, adaptation response, and fermentation conditions will be
      described. Finally, a framework for future research for anti-acid AAB will be
      provided. 

PMID- 25575806
TI  - Refining dosing by oral gavage in the dog: a protocol to harmonise welfare.
AB  - INTRODUCTION: The dog is a frequently-used, non-rodent species in the safety
      assessment of new chemical entities. We have a scientific and ethical obligation
      to ensure that the best quality of data is achieved from their use. Oral gavage
      is a technique frequently used to deliver a compound directly into the stomach.
      As with other animals, in the dog, gavage is aversive and the frequency of its
      use is a cause for welfare concern but little research has been published on the
      technique nor how to Refine it. A Welfare Assessment Framework (Hall, 2014) was
      previously developed for use with the laboratory-housed dog and a contrasting
      pattern of behaviour, cardiovascular and affective measures were found in dogs
      with positive and negative welfare. METHODS: Using the framework, this study
      compared the effects of sham dosing (used to attempt to habituate dogs to dosing)
      and a Refined training protocol against a control, no-training group to determine
      the benefit to welfare and scientific output of each technique. RESULTS: Our
      findings show that sham dosing is ineffective as a habituation technique and
      'primes' rather than desensitises dogs to dosing. Dogs in the control group
      showed few changes in parameters across the duration of the study, with some
      undesirable changes during dosing, while dogs in the Refined treatment group
      showed improvements in many parameters. DISCUSSION: It is recommended that if
      there is no time allocated for pre-study training a no-sham dosing protocol is
      used. However, brief training periods show a considerable benefit for welfare and
      quality of data to be obtained from the dogs' use.

PMID- 25575807
TI  - The relationship between the degree of cognitive impairment and retinal nerve
      fiber layer thickness.
AB  - The goal of the present study is to investigate the relationship between the
      degree of cognitive impairment and retinal nerve fiber layer (RNFL) thickness
      which is measured by the optical coherence tomography (OCT). Thirty-five patients
      with Alzheimer's disease (AD), 35 patients with mild cognitive impairment (MCI),
      and 35 healthy volunteers, between the ages of 60-87, who were examined in the
      neurology outpatient clinic among 2012-2013 were prospectively involved in our
      study. Mini mental state examination (MMSE) test, montreal cognitive assessment
      (MOCA), and also neuropsychological test batteries were used for the
      neurocognitive evaluation. RNFL thickness was measured by the OCT technique and
      the differences among groups were studied. The relationship between RNFL
      thickness and MMSE scores with demographic characteristics was investigated. RNFL
      thickness was significantly lower in AD and MCI groups compared with the control
      group (p < 0.01). No significant differences of RNFL were found between the MCI
      and the AD groups (p > 0.05). Significant correlation was found between MMSE
      scores and the RNFL values (p < 0.05). Significant thinning in RNFL along with
      age was detected (p < 0.05). In our study, it is thought that retinal nerve fiber
      degeneration and central nervous system degeneration may be concurrent according
      to the thinning of RNFL measured by OCT in AD and MCI groups. RNFL measurement
      may also be useful for early diagnosis and evaluation of the disease progression.
      Further studies are needed to optimize the utility of this method as an ocular
      biomarker in AD.

PMID- 25575808
TI  - The non glycanated endocan polypeptide slows tumor growth by inducing stromal
      inflammatory reaction.
AB  - Endocan expression is increasingly studied in various human cancers. Experimental
      evidence showed that human endocan, through its glycan chain, is implicated in
      various processes of tumor growth. We functionally characterize mouse endocan
      which is also a chondroitin sulfate proteoglycan but much less glycanated than
      human endocan. Distant domains from the O-glycanation site, located within exons
      1 and 2 determine the glycanation pattern of endocan. In opposite to the human
      homologue, overexpression of mouse endocan in HT-29 cells delayed the tumor
      appearance and reduced the tumor growth rate. This tumor growth inhibition is
      supported by non glycanated form of mouse endocan. Non glycanated human endocan
      overexpressed in HT-29, A549 or K1000 cells also exhibited an anti-tumor effect.
      Moreover, systemic delivery of non glycanated human endocan also results in HT-29
      tumor growth delay. In vitro, endocan polypeptide did not affect HT-29 cell
      proliferation, nor cell viability. In tumor tissue sections, a stromal
      inflammatory reaction was observed only in tumors overexpressing endocan
      polypeptide, and depletion of CD122+ cells was able to delete partially the anti
      tumor effect of endocan polypeptide. These results reveal a novel pathway for
      endocan in the control of tumor growth, which involves inflammatory cells of the
      innate immunity. 

PMID- 25575809
TI  - Decreased expression of GRIM-19 by DNA hypermethylation promotes aerobic
      glycolysis and cell proliferation in head and neck squamous cell carcinoma.
AB  - To identify novel tumor suppressor genes that are down-regulated by promoter
      hypermethylation in head and neck squamous cell carcinoma (HNSCC), genome-wide
      methylation profiling was performed using a methylated DNA immunoprecipitation
      (MeDIP) array in HNSCC and normal mucosa tissue samples. Promoter
      hypermethylation of the candidate gene, gene associated with retinoid-interferon
      induced mortality-19 (GRIM-19), was confirmed in HNSCC cell lines. Multivariate
      regression analysis determined that GRIM-19 hypermethylation was an independent
      significant factor for HNSCC diagnosis (OR:125.562; P < 0.001). HNSCC patients
      with lower ratio of GRIM-19/ACTB hypermethylation had increased overall and
      disease free survival. Furthermore, the optimal cutoff provided 90% sensitivity
      and 77% specificity of GRIM-19 hypermethylation as a diagnostic marker for HNSCC.
      Ectopic expression of GRIM-19 in HNSCC cells led to increased oxygen consumption,
      reduced glycolysis and decreased cell proliferation. HNSCC cells ectopically
      expressing GRIM-19 displayed increased p53 activity as well as decreased Stat3
      and HIF-1alpha activities. Moreover, GRIM-19 knockdown not only resulted in
      decreased oxygen consumption and increased aerobic glycolysis but also promoted
      cell proliferation and tumorigenic capacity in HNSCC cells. Our data indicate
      that decreased GRIM-19 expression due to promoter hypermethylation may be
      important in head and neck carcinogenesis by promoting cell proliferation and
      regulating metabolic activity. 

PMID- 25575810
TI  - Impact of age on the survival of patients with liver cancer: an analysis of
      27,255 patients in the SEER database.
AB  - BACKGROUND & AIMS: The risk of liver cancer (LC) is regarded as age dependent.
      However, the influence of age on its prognosis is controversial. The aim of our
      study was to compare the long-term survival of younger versus older patients with
      LC. METHODS: In this retrospective study, we searched Surveillance, Epidemiology,
      and End-RESULTS (SEER) population-based data and identified 27,255 patients
      diagnosed with LC between 1988 and 2003. These patients were categorized into
      younger (45 years and under) and older age (over 45 years of age) groups. Five
      year cancer specific survival data was obtained. Kaplan-Meier methods and
      multivariable Cox regression models were used to analyze long-term survival
      outcomes and risk factors. RESULTS: There were significant differences between
      groups with regards to pathologic grading, histologic type, stage, and tumor size
      (p < 0.001). The 5-year liver cancer specific survival (LCSS) rates in the
      younger and older age groups were 14.5% and 8.4%, respectively (p < 0.001 by
      univariate and multivariate analysis). A stratified analysis of age on cancer
      survival showed only localized and regional stages to be validated as independent
      predictors, but not for advanced stages. CONCLUSIONS: Compared to older patients,
      younger patients with LC have a higher LCSS after surgery, despite the poorer
      biological behavior of this carcinoma.

PMID- 25575811
TI  - Overexpression of N-terminal kinase like gene promotes tumorigenicity of
      hepatocellular carcinoma by regulating cell cycle progression and cell motility.
AB  - Amplification and overexpression of CHD1L is one of the most frequent genetic
      alterations in hepatocellular carcinoma (HCC). Here we found that one of CHD1L
      downstream targets, NTKL, was frequently upregulated in HCC, which was
      significantly correlated with vascular invasion (P = 0.012) and poor prognosis (P
      = 0.050) of HCC. ChIP assay demonstrated the binding of CHD1L to the promoter
      region of NTKL. QRT-PCR study showed that the expression of NTKL positively
      correlated with CHD1L expression in both clinical samples and cell lines.
      Functional study found that NTKL had strong oncogenic roles, including increased
      cell growth, colony formation in soft agar, and tumor formation in nude mice.
      Further study found that NTKL could promote G1/S transition by decreasing P53 and
      increasing CyclinD1 expressions. NTKL overexpression could accelerate the mitotic
      exit and chromosome segregation, which led to the cytokinesis failure and
      subsequently induced apoptosis. NTKL also regulated cell motility by facilitating
      philopodia and lamellipodia formation through regulating F-actin reorganization
      and the phosphorylation of small GTPase Rac1/cdc42. Using co-IP and mass
      spectrometry approach, we identified the large GTPase dynamin2 as an interacting
      protein of NTKL, which might be responsible for the phenotype alterations caused
      by NTKL overexpression, such as cytokinesis failure, increased cell motility and
      abnormal of cell division. 

PMID- 25575812
TI  - Identification of the oncogenic kinase TOPK/PBK as a master mitotic regulator of
      C2H2 zinc finger proteins.
AB  - TOPK/PBK is an oncogenic kinase upregulated in most human cancers and its high
      expression correlates with poor prognosis. TOPK is known to be activated by Cdk1
      and needed for mitotic cell division; however, its mitotic functions are not yet
      fully understood. In this study, we show that TOPK plays a global mitotic role by
      simultaneously regulating hundreds of DNA binding proteins. C2H2 zinc finger
      proteins (ZFPs) constitute the largest family of human proteins. All C2H2 ZFPs
      contain a highly conserved linker sequence joining their multi-zinc finger
      domains. We have previously shown that phosphorylation of this conserved motif
      serves as a global mechanism for the coordinate dissociation of C2H2 ZFPs from
      condensing chromatin, during mitosis. Here, using a panel of kinase inhibitors,
      we identified K252a as a potent inhibitor of mitotic ZFP linker phosphorylation.
      We generated a biotinylated form of K252a and used it to purify candidate
      kinases. From these candidates we identified TOPK/PBK, in vitro and in vivo, as
      the master ZFP linker kinase. Furthermore, we show precise temporal correlation
      between TOPK activating phosphorylation by Cdk1 and linker phosphorylation in
      mitosis. The identification of this fundamental role of TOPK underscores its
      significance as a promising novel target of cancer therapeutics. 

PMID- 25575813
TI  - Gene expression analysis of head and neck squamous cell carcinoma survival and
      recurrence.
AB  - The squamous cell carcinomas represent about 90 % of all head and neck cancers,
      ranking the sixth most common human cancer. Approximately 450,000 of new cases of
      head and neck squamous cell carcinoma (HNSCC) are diagnosed every year.
      Unfortunately, because of diagnosis at the advanced stages and early metastasis
      to the lymph nodes, the HNSCC is associated with very high death rate.
      Identification of signature biomarkers and molecularly targeted therapies could
      provide more effective and specific cancer treatment, prevent recurrence, and
      increase survival rate. We used paired tumor and adjacent normal tissue samples
      to screen with RT2 ProfilerTM PCR Array Human Cancer PathwayFinderTM . Total of
      20 up-regulated genes and two down-regulated genes were screened out. Out of 22
      genes, 12 genes were subsequently validated to be significantly altered in the
      HNSCC; the samples were from all 41 patients. Five year survival and recurrence
      selected genes that could represent the biomarkers of survival and recurrence of
      the disease. We believe that comprehensive understanding of the unique genetic
      characteristics of HNSCC could provide novel diagnostic biomarkers and meet the
      requirement for molecular-targeted therapy for the HNSCC. 

PMID- 25575814
TI  - MIG-7 and phosphorylated prohibitin coordinately regulate lung cancer
      invasion/metastasis.
AB  - Growth factors and COX-2/PGE2 enhance lung cancer invasion/metastasis via
      PI3K/Akt and RAS/Raf. Here, we explored their mechanism of action further. We
      found first that higher levels of migration inducting gene-7 protein (MIG-7) and
      PHB phosphorylated at threonine 258 (phospho-PHBT258) are positively correlated
      with advanced stages of human lung cancer in tissue microarray. PGE2 or growth
      factors such as EGF, HGF and IGF-1 increased complex formation of phospho-PHBT258
      with Ras, phospho-AktS473, phospho-Raf-1S338, MEKK1 and IKKalpha/betaS176/180 in
      the raft domain transiently within 1 hour and MIG-7 in the cytosol 12-24 hours
      later. Association of phospho-PHBT258 with MEKK1 but not MEKK3 activates
      IKK/IkappaB/NF-kappaB and MEK/ERK to increase cellular COX-2/PGE2 and an E
      cadherin suppressor Snail leading to enhancement of epithelial-mesenchymal
      transition (EMT) and lung cancer migration/invasion. MIG-7, on the other hand,
      was induced by growth factors and PGE2 via Akt/GSK-3beta in a phospho-PHBT258
      independent manner. MIG-7 increased two E-cadherin suppressors ZEB-1 and Twist to
      enhance EMT and cancer migration/invasion. Downregulating phospho-PHBT258 and MIG
      7 had an additive effect on attenuating lung cancer invasion/metastasis and
      prolonging the survival of xenograft mice. Phospho-PHBT258 and MIG-7 may thus
      play complementary roles in the initiation and sustainment of the effects of
      growth factors and COX-2/PGE2 on cancer invasion/metastasis.

PMID- 25575815
TI  - Tumor-targeting Salmonella typhimurium A1-R arrests growth of breast-cancer brain
      metastasis.
AB  - Brain metastasis is a morbid, treatment-resistant, end-stage frequent occurrence
      in breast cancer patients. The aim of this study was to evaluate the efficacy of
      tumor-targeting Salmonella typhimurium A1-R on breast cancer brain metastases.
      High brain-metastatic variants of murine 4T1 breast cancer cells expressing red
      fluorescent protein (RFP) were injected orthotopically in the mammary fat pad in
      non-transgenic nude mice or in the left ventricle of non-transgenic nude mice and
      transgenic nude mice expressing nestin-driven green fluorescent protein (ND-GFP).
      ND-GFP mice express GFP in nascent blood vessels. In the orthotopically-injected
      mice, the primary tumor was surgically-resected in order to allow brain
      metastasis to develop. At various time points, the tumors and vasculature in the
      brain were imaged by confocal and stereo fluorescence microscopy. Some of the
      breast cancer cells that reached the brain extravasated and grew perivascularly
      and some of the cells proliferated within the vasculature. S. typhimurium A1-R
      significantly inhibited brain metastasis in both metastatic models and increased
      survival of the orthotopically-transplanted, primary-tumor-resected mice
      (p<0.05). The results of the present study suggest the clinical potential of
      bacterial therapy of breast cancer brain metastasis. 

PMID- 25575816
TI  - Dichloroacetate blocks aerobic glycolytic adaptation to attenuated measles virus
      and promotes viral replication leading to enhanced oncolysis in glioblastoma.
AB  - Targeting reprogrammed energy metabolism such as aerobic glycolysis is a
      potential strategy for cancer treatment. However, tumors exhibiting low-rate
      glycolysis or metabolic heterogeneity might be resistant to such treatment. We
      hypothesized that a therapeutic modality that drove cancer cells to high-rate
      glycolysis might sensitize cancer cells to interference directed against
      metabolic flux. In this study, we found that attenuated oncolytic measles virus
      Edmonston strain (MV-Edm) caused glioblastoma cells to shift to high-rate aerobic
      glycolysis; this adaptation was blocked by dichloroacetate (DCA), an inhibitor of
      glycolysis, leading to profound cell death of cancer cells but not of normal
      cells. DCA enhanced viral replication by mitigating mitochondrial antiviral
      signaling protein (MAVS)-mediated innate immune responses. In a subcutaneous
      glioblastoma (GBM) xenograft mouse model, low-dose MV-Edm and DCA significantly
      inhibited tumor growth in vivo. We found that DCA impaired glycolysis (blocking
      bioenergetic generation) and enhanced viral replication (increasing bioenergetic
      consumption), which, in combination, accelerated bioenergetic exhaustion leading
      to necrotic cell death. Taken together, oncolytic MV-Edm sensitized cancer cells
      to DCA, and in parallel, DCA promoted viral replication, thus, improving
      oncolysis. This novel therapeutic approach should be readily incorporated into
      clinical trials. 

PMID- 25575817
TI  - Histone demethylase RBP2 decreases miR-21 in blast crisis of chronic myeloid
      leukemia.
AB  - Chronic myeloid leukemia in the blastic phase (CML-BP) responds poorly to
      clinical treatments and is usually fatal. In this study, we found that the
      histone H3 lysine 4 (H3K4) demethylase RBP2 (also called JARID1A and KDM5A) is
      underexpressed in CML-BP. The RBP2 histone demethylase stimulates leukemia cell
      differentiation and inhibits cell proliferation. We identified miR-21 was
      directly downregulated by RBP2 and found that miR-21 downregulated PDCD4
      expression in leukemia cells. By binding to miR-21 promoter and by demethylating
      of trimethylated H3K4 at the miR-21 locus, RBP2 downregulated miR-21 expression.
      This in turn activated PDCD4. In conclusion, RBP2 epigenetically downregulated
      miR-21 in blast transformation of CML. 

PMID- 25575818
TI  - Simplify p53: just an activator.

PMID- 25575819
TI  - TORC2 inhibition may boost DNA-damaging chemotherapy.
AB  - Comment on: Selvarajah J, Elia A, Carroll VA, Moumen A. DNA damage-induced S and
      G2/M cell cycle arrest requires mTORC2-dependent regulation of Chk1. Oncotarget.
      2015; 6:427-40. 

PMID- 25575820
TI  - Mcl-1 and tumor cell persistence.

PMID- 25575822
TI  - Methyl-beta-cyclodextrin up-regulates collagen I expression in chronologically
      aged skin via its anti-caveolin-1 activity.
AB  - Caveolin-1 (Cav-1) is one of the key molecules to modulate collagen metabolism in
      the skin. This study aimed to unravel the relationship between Cav-1 and collagen
      levels in the aged skin, and also to evaluate a new role of anti-Cav-1 agent as a
      collagen-modulating agent. A negative correlation between Cav-1 and collagen I
      (COL I) was detected in chronologically aged skin of humans and mice, which was
      further confirmed by Cav-1 knock-down or knock-out experiments. Next, we tested
      whether methyl-beta-cyclodextrin (MbetaCD) as a chemical Cav-1 inhibitor could be
      developed as a collagen-modulating agent in the skin. Testing different
      conditions of MbetaCD injection via the intra-dermal route revealed that 2.5%
      MbetaCD administered twice per week for two months showed a potent COL I-up
      regulating activity, leading to the increase of skin thickness (P < 0.05) without
      adverse reactions such as skin fibrosis. In human dermal fibroblasts, MbetaCD
      treatment induced up-regulated COL I and down-regulated Cav-1, supporting the
      results of mouse experiments. Collectively, MbetaCD has a COL I-enhancing
      activity in chronologically-aged skin, where Cav-1 acts as a brake in COL I
      expression, suggesting its potential role for an anti-aging agent.

PMID- 25575821
TI  - Neoalbaconol induces cell death through necroptosis by regulating RIPK-dependent
      autocrine TNFalpha and ROS production.
AB  - Necroptosis/regulated necrosis is a caspase-independent, but receptor interacting
      protein kinase (RIPK)-dependent form of cell death. In previous studies,
      neoalbaconol (NA), a constituent extracted from Albatrellus confluens, was
      demonstrated to induce necroptosis in some cancer cell lines. The molecular
      mechanism of NA-induced necroptosis is described in this research study. We
      determined that NA-induced cell death is partly dependent on tumor necrosis
      factor alpha (TNFalpha) feed-forward signaling. More importantly, NA abolished
      the ubiquitination of RIPK1 by down-regulating E3 ubiquitin ligases, cellular
      inhibitors of apoptosis protein 1/2 (cIAP1/2) and TNFalpha receptor-associated
      factors (TRAFs). The suppression of RIPK1 ubiquitination induced the activation
      of the non-canonical nuclear factor-kappaB (NF-kappaB) pathway and stimulated the
      transcription of TNFalpha. Moreover, we also found that NA caused RIPK3-mediated
      reactive oxygen species (ROS) production and contribution to cell death. Taken
      together, these results suggested that two distinct mechanisms are involved in NA
      induced necroptosis and include RIPK1/NF-kappaB-dependent expression of TNFalpha
      and RIPK3-dependent generation of ROS. 

PMID- 25575823
TI  - DNA damage induces GDNF secretion in the tumor microenvironment with paracrine
      effects promoting prostate cancer treatment resistance.
AB  - Though metastatic cancers often initially respond to genotoxic therapeutics,
      acquired resistance is common. In addition to cytotoxic effects on tumor cells,
      DNA damaging agents such as ionizing radiation and chemotherapy induce injury in
      benign cells of the tumor microenvironment resulting in the production of
      paracrine-acting factors capable of promoting tumor resistance phenotypes. In
      studies designed to characterize the responses of prostate and bone stromal cells
      to genotoxic stress, we found that transcripts encoding glial cell line-derived
      neurotrophic factor (GDNF) increased several fold following exposures to
      cytotoxic agents including radiation, the topoisomerase inhibitor mitoxantrone
      and the microtubule poison docetaxel. Fibroblast GDNF exerted paracrine effects
      toward prostate cancer cells resulting in enhanced tumor cell proliferation and
      invasion, and these effects were concordant with the expression of known GDNF
      receptors GFRA1 and RET. Exposure to GDNF also induced tumor cell resistance to
      mitoxantrone and docetaxel chemotherapy. Together, these findings support an
      important role for tumor microenvironment damage responses in modulating
      treatment resistance and identify the GDNF signaling pathway as a potential
      target for improving responses to conventional genotoxic therapeutics. 

PMID- 25575824
TI  - Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer
      patients with a novel, high-sensitivity multiplexed mutation detection platform.
AB  - BACKGROUND: Circulating tumor DNA (ctDNA) holds promise as a non-invasive means
      for tumor monitoring in solid malignancies. Assays with high sensitivity and
      multiplexed analysis of mutations are needed to enable broad application.
      METHODS: We developed a new assay based on sequence-specific synchronous
      coefficient of drag alteration (SCODA) technology, which enriches for mutant DNA
      to achieve high sensitivity and specificity. This assay was applied to plasma and
      tumor tissue from non-metastatic and metastatic colorectal cancer (CRC) patients,
      including patients undergoing surgical resection for CRC liver metastases.
      RESULTS: Across multiple characterization experiments, the assay demonstrated a
      limit of detection of 0.001% (1 molecule in 100,000) for the majority of the 46
      mutations in the panel. In CRC patient samples (n=38), detected mutations were
      concordant in tissue and plasma for 93% of metastatic patients versus 54% of non
      metastatic patients. For three patients, ctDNA identified additional mutations
      not detected in tumor tissue. In patients undergoing liver metastatectomy, ctDNA
      anticipated tumor recurrence earlier than carcinoembryonic antigen (CEA) value or
      imaging. CONCLUSIONS: The multiplexed SCODA mutation enrichment and detection
      method can be applied to mutation profiling and quantitation of ctDNA, and is
      likely to have particular utility in the metastatic setting, including patients
      undergoing metastatectomy.

PMID- 25575826
TI  - Limisphaera ngatamarikiensis gen. nov., sp. nov., a thermophilic, pink-pigmented
      coccus isolated from subaqueous mud of a geothermal hotspring.
AB  - A novel bacterial strain, NGM72.4(T), was isolated from a hot spring in the
      Ngatamariki geothermal field, New Zealand. Phylogenetic analysis based on 16S
      rRNA gene sequences grouped it into the phylum Verrucomicrobia and class level
      group 3 (also known as OPB35 soil group). NGM72.4(T) stained Gram-negative, and
      was catalase- and oxidase-positive. Cells were small cocci, 0.5-0.8 um in
      diameter, which were motile by means of single flagella. Transmission electron
      micrograph (TEM) imaging showed an unusual pirellulosome-like intracytoplasmic
      membrane. The peptidoglycan content was very small with only trace levels of
      diaminopimelic acid detected. No peptidoglycan structure was visible in TEM
      imaging. The predominant isoprenoid quinone was MK-7 (92%). The major fatty acids
      (>15%) were C(16 : 0), anteiso-C(15 : 0), iso-C(16 : 0) and anteiso-C(17 : 0).
      Major phospholipids were phosphatidylethanolamine (PE),
      phosphatidylmonomethylethanolamine (PMME) and cardiolipin (CL), and a novel
      analogous series of phospholipids where diacylglycerol was replaced with
      diacylserinol (sPE, sPMME, sCL). The DNA G+C content was 65.6 mol%. Cells
      displayed an oxidative chemoheterotrophic metabolism. NGM72.4(T) is a strictly
      aerobic thermophile (growth optimum 60-65  degrees C), has a slightly
      alkaliphilic pH growth optimum (optimum pH 8.1-8.4) and has a NaCl tolerance of
      up to 8 g l(-1). Colonies were small, circular and pigmented pale pink. The
      distinct phylogenetic position and phenotypic traits of strain NGM72.4(T)
      distinguish it from all other described species of the phylum Verrucomicrobia
      and, therefore, it is considered to represent a novel species in a new genus for
      which we propose the name Limisphaera ngatamarikiensis gen. nov., sp. nov. The
      type strain is NGM72.4(T) ( = ICMP 20182(T) = DSM 27329(T)).

PMID- 25575825
TI  - Inhibition of the Warburg effect with a natural compound reveals a novel
      measurement for determining the metastatic potential of breast cancers.
AB  - Metabolism is an important differentiating feature of cancer cells. Lactate
      dehydrogenases (LDH) A/B are metabolically important proteins and are involved in
      the critical step of inter-conversion of lactate to pyruvate. Panepoxydone (PP),
      a natural NF-kB inhibitor, significantly reduces the oxygen consumption and
      lactate production of MCF-7 and triple negative (MDA-MB-231, MDA-MB-468 and MDA
      MB-453) breast cancer cells. We further observed that PP inhibited mitochondrial
      membrane potential and the ATP synthesis using flow cytometry. PP also up
      regulated LDH-B and down-regulated LDH-A expression levels in all breast cancer
      cells to similar levels observed in HMEC cells. Over-expression of LDH-B in
      cancer cell lines leads to enhanced apoptosis, mitochondrial damage, and reduced
      cell migration. Analyzing the patient data set GDS4069 available on the GEO
      website, we observed 100% of non TNBC and 60% of TNBC patients had less LDH-B
      expression than LDH-A expression levels. Herein we report a new term called
      Glycolytic index, a novel method to calculate utilization of oxidative
      phosphorylation in breast cancer cells through measuring the ratio of the LDH-B
      to LDH-A. Furthermore, inhibitors of NF-kB could serve as a therapeutic agent for
      targeting metabolism and for the treatment of triple negative breast cancer. 

PMID- 25575827
TI  - Methanoculleus taiwanensis sp. nov., a methanogen isolated from deep marine
      sediment at the deformation front area near Taiwan.
AB  - A mesophilic, hydrogenotrophic methanogen, strain CYW4(T), was isolated from deep
      sea sediment obtained by the Ocean Researcher I cruiser, ORI-961, in 2011. The
      sediment was from the deformation front area offshore of south-western Taiwan.
      Here, seismic reflections indicated that methane hydrates were abundant. The
      methanogenic substrates utilized by strain CYW4(T) were formate and H2/CO2, but
      not acetate, secondary alcohols, methylamines, methanol and ethanol. Cells of
      strain CYW4(T) were non-motile, irregular cocci and 0.6-1.5 um in diameter. The S
      layer protein had an Mr of 112 000. The optimum growth conditions were at 37 
      degrees C, pH 8.1 and 0.08 M NaCl. Growth of the strain was stimulated by
      acetate. The G+C content of the chromosomal DNA of strain CYW4(T) was 61 mol%.
      Phylogenetic analysis revealed that strain CYW4(T) was most closely related to
      Methanoculleus marisnigri JR1(T) (96.82 % 16S rRNA gene sequence similarity).
      Based on the morphological, phenotypic and phylogenetic characteristics presented
      here, it is evident that strain CYW4(T) represents a novel species of the genus
      Methanoculleus, and the name Methanoculleus taiwanensis sp. nov. is proposed. The
      type strain is CYW4(T) ( = BCRC AR10043(T) = NBRC 110782(T)). The optical density
      of cultures of strain CYW4(T) dropped abruptly upon entering the stationary
      growth phase. During this time numerous particles of approximately 50 nm in
      diameter were observed on and around the cells. This suggests that strain CYW4(T)
      harbours a lytic virus that is induced in the stationary phase, which is of
      interest because only a few lytic viruses have been reported in methanogens. 

PMID- 25575828
TI  - Burkholderia susongensis sp. nov., a mineral-weathering bacterium isolated from
      weathered rock surface.
AB  - A novel type of mineral-weathering bacterium was isolated from the weathered
      surface of rock (mica schist) collected from Susong (Anhui, China). Cells of
      strain L226(T) were Gram-stain-negative. The strain grew optimally at 30  degrees
      C, with 1 % (w/v) NaCl and at pH 7.0 in trypticase soy broth. On the basis of 16S
      rRNA gene phylogeny, strain L226(T) was shown to belong to the genus Burkholderia
      and the closest phylogenetic relatives were Burkholderia sprentiae WSM5005(T)
      (98.3 %), Burkholderia acidipaludis NBRC 101816(T) (98.2 %), Burkholderia tuberum
      STM678(T) (97.2 %) and Burkholderia diazotrophica JPY461(T) (97.1 %). The DNA G+C
      content was 63.5 mol% and the respiratory quinone was Q-8. The major fatty acids
      were C16 : 0, C17 : 0 cyclo and C19 : 0 cyclo omega8c. The polar lipid profile of
      strain L226(T) consisted of a mixture of phosphatidylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol, unknown lipids and unidentified
      aminophospholipids. Based on the low level of DNA-DNA relatedness (ranging from
      25.8 % to 34.4 %) to the tested type strains of species of the genus Burkholderia
      and unique phenotypic characteristics, it is suggested that strain L226(T)
      represents a novel species of the genus Burkholderia, for which the name
      Burkholderia susongensis sp. nov., is proposed. The type strain is L226(T) ( =
      CCTCC AB2014142(T) = JCM 30231(T)). 

PMID- 25575829
TI  - Gynuella sunshinyii gen. nov., sp. nov., an antifungal rhizobacterium isolated
      from a halophyte, Carex scabrifolia Steud.
AB  - An antifungal bacterial strain, designated YC6258(T), was isolated from the
      rhizosphere of a halophyte (Carex scabrifolia Steud.) growing in a tidal flat
      area of Namhae Island, Korea. Cells of the strain were Gram-stain-negative,
      facultatively anaerobic, moderately halophilic, rod-shaped and motile by a single
      polar flagellum. Phylogenetic analysis based on 16S rRNA gene sequences showed
      that strain YC6258(T) formed a phyletic lineage distinct from members of the most
      closely related genera, Saccharospirillum and Reinekea, with less than 91.2 %
      sequence similarities. The major cellular fatty acids were C18 : 1omega7c, C16 :
      0 and Summed feature 3 (C16 : 1omega7c/ C16 : 1omega6c). The quinone system of
      strain YC6258(T) consisted mainly of ubiquinone Q-8. The polar lipid profile
      exhibited phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol
      and unknown lipids. The DNA G+C content was 48.9 mol%. Based on the phylogenetic
      and phenotypic characteristics, strain YC6258(T) should be classified as a
      representative of a novel species in a novel genus for which the name Gynuella
      sunshinyii gen. nov., sp. nov. is proposed. The type strain is YC6258(T) (KCCM
      43015(T) = NBRC 109345(T)). 

PMID- 25575830
TI  - Establishment of a mass gathering department within health service systems.

PMID- 25575831
TI  - Tropheryma whipplei as a causative agent of travelers' diarrhea: further studies
      required.

PMID- 25575832
TI  - Response to 'Re: Aneurysmal degeneration of the inflow artery after arteriovenous
      access for hemodialysis'.

PMID- 25575833
TI  - The impact of early pelvic and lower limb reperfusion and attentive peri
      operative management on the incidence of spinal cord ischemia during
      thoracoabdominal aortic aneurysm endovascular repair.
AB  - OBJECTIVE/BACKGROUND: Spinal cord ischemia (SCI) is a devastating complication
      following endovascular thoracoabdominal aortic aneurysm (TAAA) repair. In an
      attempt to reduce its incidence two peri-procedural changes were implemented by
      the authors in January 2010: (i) all large sheaths are withdrawn from the iliac
      arteries immediately after deploying the central device and before cannulation
      and branch extension to the visceral vessels; (ii) the peri-operative protocol
      has been modified in an attempt to optimize oxygen delivery to the sensitive
      cells of the cord (aggressive blood and platelet transfusion, median arterial
      pressure monitoring >85 mmHg, and systematic cerebrospinal fluid drainage).
      METHODS: Between October 2004 and December 2013, 204 endovascular TAAA repairs
      were performed using custom made devices manufactured with branches and
      fenestrations to maintain visceral vessel perfusion. Data from all of these
      procedures were prospectively collected in an electronic database. Early post
      operative results in patients treated before (group 1, n = 43) and after (group
      2, n = 161 patients) implementation of the modified implantation and peri
      operative protocols were compared. RESULTS: Patients in groups 1 and 2 had
      similar comorbidities (median age at repair 70.9 years [range 65.2-77.0 years]),
      aneurysm characteristics (median diameter 58.5 mm [range 53-65 mm]), and length
      of procedure (median 190 minutes [range 150-240 minutes]). The 30 day mortality
      rate was 11.6% in group 1 versus 5.6% in group 2 (p = .09). The SCI rate was
      14.0% versus 1.2% (p < .01). If type IV TAAAs were excluded from this analysis,
      the SCI rate was 25.0% (6/24 patients) in group 1 versus 2.1% (2/95 patients) in
      group 2 (p < .01). CONCLUSION: The early restoration of arterial flow to the
      pelvis and lower limbs, and aggressive peri-operative management significantly
      reduces SCI following type I-III TAAA endovascular repair. With the use of these
      modified protocols, extensive TAAA endovascular repairs are associated with low
      rates of SCI.

PMID- 25575835
TI  - Dermatologic disorders in 118 patients with autoimmune (immunoglobulin G4
      related) pancreatitis: a retrospective cohort analysis.
AB  - BACKGROUND: Autoimmune pancreatitis is the prototypical manifestation of
      immunoglobulin G4-related disease, a fibroinflammatory syndrome that can affect
      virtually any organ. Rarely, skin involvement has been reported in immunoglobulin
      G4-related disease. Isolated case reports have described other distinct
      associated dermatoses. OBJECTIVE: Our objective was to determine the frequency
      and nature of dermatologic manifestations of immunoglobulin G4-related disease in
      patients with autoimmune pancreatitis. METHODS: Retrospective analysis of
      dermatologic conditions of patients with autoimmune pancreatitis. RESULTS: Among
      the 118 identified patients, 31 (26.3%) had a dermatologic diagnosis [mean
      (standard deviation; SD) follow-up 5.9 (4.6) years]. Two patients (1.7%) had
      necrobiotic xanthogranuloma; three (2.5%) had another xanthomatous or
      xanthogranulomatous process. One patient (0.8%) had pemphigus erythematosus. No
      patient had immunoglobulin G4-related skin disease. CONCLUSION: Skin involvement
      in immunoglobulin G4-related disease appears to be rare. A disproportionately
      high number of patients had xanthomatous or xanthogranulomatous processes,
      including necrobiotic xanthogranuloma. It remains unclear whether the association
      between immunoglobulin G4-related disease and necrobiotic xanthogranuloma or
      other xantho(granulo)matous processes represents shared pathophysiology, a mutual
      underlying driver, or coincidence, though the results of this study cast doubt on
      the latter. Although pemphigus was not reported in immunoglobulin G4-related
      disease previously, the prominent role of the immunoglobulin G4 subclass in each
      condition makes this association intriguing.

PMID- 25575834
TI  - Comparison of backbone dynamics of the type III antifreeze protein and antifreeze
      like domain of human sialic acid synthase.
AB  - Antifreeze proteins (AFPs) are found in a variety of cold-adapted (psychrophilic)
      organisms to promote survival at subzero temperatures by binding to ice crystals
      and decreasing the freezing temperature of body fluids. The type III AFPs are
      small globular proteins that consist of one alpha-helix, three 3(10)-helices, and
      two beta-strands. Sialic acids play important roles in a variety of biological
      functions, such as development, recognition, and cell adhesion and are
      synthesized by conserved enzymatic pathways that include sialic acid synthase
      (SAS). SAS consists of an N-terminal catalytic domain and a C-terminal antifreeze
      like (AFL) domain, which is similar to the type III AFPs. Despite having very
      similar structures, AFL and the type III AFPs exhibit very different temperature
      dependent stability and activity. In this study, we have performed backbone
      dynamics analyses of a type III AFP (HPLC12 isoform) and the AFL domain of human
      SAS (hAFL) at various temperatures. We also characterized the structural/dynamic
      properties of the ice-binding surfaces by analyzing the temperature gradient of
      the amide proton chemical shift and its correlation with chemical shift deviation
      from random coil. The dynamic properties of the two proteins were very different
      from each other. While HPLC12 was mostly rigid with a few residues exhibiting
      slow motions, hAFL showed fast internal motions at low temperature. Our results
      provide insight into the molecular basis of thermostability and structural
      flexibility in homologous psychrophilic HPLC12 and mesophilic hAFL proteins.

PMID- 25575836
TI  - Relocation of a rust resistance gene R 2 and its marker-assisted gene pyramiding
      in confection sunflower (Helianthus annuus L.).
AB  - KEY MESSAGE: The rust resistance gene R 2 was reassigned to linkage group 14 of
      the sunflower genome. DNA markers linked to R 2 were identified and used for
      marker-assisted gene pyramiding in a confection type genetic background. Due to
      the frequent evolution of new pathogen races, sunflower rust is a recurring
      threat to sunflower production worldwide. The inbred line Morden Cross 29 (MC29)
      carries the rust resistance gene, R 2 , conferring resistance to numerous races
      of rust fungus in the US, Canada, and Australia, and can be used as a broad
      spectrum resistance resource. Based on phenotypic assessments and SSR marker
      analyses on the 117 F2 individuals derived from a cross of HA 89 with MC29
      (USDA), R 2 was mapped to linkage group (LG) 14 of the sunflower, and not to the
      previously reported location on LG9. The closest SSR marker HT567 was located at
      4.3 cM distal to R 2 . Furthermore, 36 selected SNP markers from LG14 were used
      to saturate the R 2 region. Two SNP markers, NSA_002316 and SFW01272, flanked R 2
      at a genetic distance of 2.8 and 1.8 cM, respectively. Of the three closely
      linked markers, SFW00211 amplified an allele specific for the presence of R 2 in
      a marker validation set of 46 breeding lines, and SFW01272 was also shown to be
      diagnostic for R 2 . These newly developed markers, together with the previously
      identified markers linked to the gene R 13a , were used to screen 524 F2
      individuals from a cross of a confection R 2 line and HA-R6 carrying R 13a .
      Eleven homozygous double-resistant F2 plants with the gene combination of R 2 and
      R 13a were obtained. This double-resistant line will be extremely useful in
      confection sunflower, where few rust R genes are available, risking evolution of
      new virulence phenotypes and further disease epidemics.

PMID- 25575837
TI  - Spot form of net blotch resistance in barley is under complex genetic control.
AB  - KEY MESSAGE: Evaluation of resistance to Pyrenophora teres f. maculata in barley
      breeding populations via association mapping revealed a complex genetic
      architecture comprising a mixture of major and minor effect genes. In the search
      for stable resistance to spot form of net blotch (Pyrenophora teres f. maculata,
      SFNB), association mapping was conducted on four independent barley (Hordeum
      vulgare L.) breeding populations comprising a total of 898 unique elite breeding
      lines from the Northern Region Barley Breeding Program in Australia for discovery
      of quantitative trait loci (QTL) influencing resistance at seedling and adult
      plant growth stages. A total of 29 significant QTL were validated across multiple
      breeding populations, with 22 conferring resistance at both seedling and adult
      plant growth stages. The remaining 7 QTL conferred resistance at either seedling
      (2 QTL) or adult plant (5 QTL) growth stages only. These 29 QTL represented 24
      unique genomic regions, of which five were found to co-locate with previously
      identified QTL for SFNB. The results indicated that SFNB resistance is controlled
      by a large number of QTL varying in effect size with large effects QTL on
      chromosome 7H. A large proportion of the QTL acted in the same direction for both
      seedling and adult responses, suggesting that phenotypic selection for SFNB
      resistance performed at either growth stage could achieve adequate levels of
      resistance. However, the accumulation of specific resistance alleles on several
      chromosomes must be considered in molecular breeding selection strategies.

PMID- 25575838
TI  - Erratum to: Genome-wide association study (GWAS) of carbon isotope ratio
      (delta(13)C) in diverse soybean [Glycine max (L.) Merr.] genotypes.

PMID- 25575839
TI  - Large effect QTL explain natural phenotypic variation for the developmental
      timing of vegetative phase change in maize (Zea mays L.).
AB  - KEY MESSAGE: Natural variation for the timing of vegetative phase change in maize
      is controlled by several large effect loci, one corresponding to Glossy15 , a
      gene known for regulating juvenile tissue traits. Vegetative phase change is an
      intrinsic component of developmental programs in plants. Juvenile and adult
      vegetative tissues in grasses differ dramatically in their anatomical and
      biochemical composition affecting the utility of specific genotypes as animal
      feed and biofuel feedstock. The molecular network controlling the process of
      developmental transition is incompletely characterized. In this study, we used
      scoring for juvenile and adult epicuticular wax as an entry point to discover
      quantitative trait loci (QTL) controlling phenotypic variation for the
      developmental timing of juvenile to adult transition in maize. We scored the last
      leaf with juvenile wax on 25 recombinant inbred line families of the B73
      reference Nested Association Mapping (NAM) population and the intermated B73*Mo17
      (IBM) population across multiple seasons. A total of 13 unique QTL were
      identified through genome-wide association analysis across the NAM populations,
      three of which have large effects. A QTL located on chromosome nine had the most
      significant SNPs within Glossy15, a gene controlling expression of juvenile leaf
      traits. The second large effect QTL is located on chromosome two. The most
      significant SNP in this QTL is located adjacent to a homolog of the Arabidopsis
      transcription factor, enhanced downy mildew-2, which has been shown to promote
      the transition from juvenile to adult vegetative phase. Overall, these results
      show that several major QTL and potential candidate genes underlie the extensive
      natural variation for this developmental trait.

PMID- 25575840
TI  - Genetic mapping of the nulliplex-branch gene (gb_nb1) in cotton using next
      generation sequencing.
AB  - KEY MESSAGE: Using bulked segregant analysis based on next-generation sequencing,
      the recessive nulliplex-branch gene was mapped between two SNP markers ~600 kb
      apart. In a "nulliplex-branch" cotton mutant, most of the flowers arise directly
      from leaf axils on the main shoot, which usually does not have a fruiting branch.
      A nulliplex-branch is a useful trait by which to study cotton architecture;
      however, the genetic basis of this mutant has remained elusive. In this study,
      bulked segregant analysis combined with next-generation sequencing technology was
      used to finely map the underlying genes that result in a nulliplex-branch plant.
      The nulliplex-branch Pima cotton variety, Xinhai-18, was crossed with the normal
      branch upland cotton line, TM-1, resulting in an F2 population. The nulliplex
      branch trait was found to be controlled by the recessive gene gb_nb1. Allelic
      single-nucleotide polymorphisms (SNPs) were discovered by reduced-representation
      sequencing between the parents, and their profiles were also characterized in the
      nulliplex-branch and normal branch bulks constructed using the F2 plants. A
      candidate ~9.0 Mb-long region comprising 42 SNP markers was found to be
      associated with gb_nb1, which helped localize it at the ~600-kb interval on Chr
      16 by segregation analysis in the F2 population. The closely linked markers with
      gb_nb1 developed in this study will facilitate the marker-assisted selection of
      the nulliplex-branch trait, and the fine map constructed will accelerate map
      based cloning of gb_nb1.

PMID- 25575841
TI  - Management of complications and compromised free flaps following major head and
      neck surgery.
AB  - Microvascular free flaps are preferred for most major head and neck
      reconstruction surgeries because of better functional outcomes, improved
      esthetics, and generally higher success rates. Numerous studies have investigated
      measures to prevent flap loss, but few have evaluated the optimal treatment for
      free flap complications. This study aimed to determine the complication rate
      after free flap reconstructions and discusses our management strategies. Medical
      records of 260 consecutive patients who underwent free flap reconstructions for
      head and neck defects between July 2006 and June 2010 were retrospectively
      reviewed for patient and surgical characteristics and postoperative
      complications. The results revealed that microvascular free flaps were extremely
      reliable, with a 3.5 % incidence of flap failure. There were 78 surgical site
      complications. The most common complication was neck wound infection, followed by
      dehiscence, vascular congestion, abscess, flap necrosis, hematoma,
      osteoradionecrosis, and brisk bleeding. Twenty patients with poor wound healing
      received hyperbaric oxygen therapy, which was ineffective in three patients who
      eventually experienced complete flap loss. Eleven patients with vascular
      congestion underwent medicinal leech therapy, which was effective. Among the 78
      patients with complications, 44 required repeat surgery, which was performed for
      postoperative brisk bleeding in three. Eventually, ten patients experienced
      partial flap loss and nine experienced complete flap loss, with the latter
      requiring subsequent pectoralis major flap reconstruction. Microvascular free
      flap reconstruction represents an essential and reliable technique for head and
      neck defects and allows surgeons to perform radical resection with satisfactory
      functional results and acceptable complication rates.

PMID- 25575842
TI  - Tumor site and disease stage as predictors of quality of life in head and neck
      cancer: a prospective study on patients treated with surgery or combined therapy
      with surgery and radiotherapy or radiochemotherapy.
AB  - In this prospective study, we compared the short-term quality of life (QOL) of
      two subgroups of head and neck cancers: oropharyngeal and laryngeal cancers.
      Patients treated with curative surgery, were asked to participate in the study
      using the EORTC QLQ-C30 and H&N35 questionnaires to examine QOL. The oropharynx
      group consisted of 32 (48 %) patients, while the larynx group consisted of 35 (52
      %) patients. All patients were treated with either curative surgery alone or
      curative surgery combined with adjuvant radiotherapy or radiochemotherapy. The
      questionnaires were handed out pre- and post-therapy (10 months). At baseline, an
      impaired overall QOL (=EORTC QLQ-C30 global score) with a value of 53.4 for the
      whole patient collective was found; the overall QOL after 10 months improved
      (60.2, p < 0.05). Between the two patient groups, there was no difference in the
      global score after 10 months. The oropharynx patients described more problems
      with fatigue and oral cavity associated. The main symptoms in the larynx group
      were loss of sensual function and coughing. The present investigation revealed
      that the general post-therapy QOL in two subgroups of head and neck cancer
      reached a satisfying level.

PMID- 25575843
TI  - Reduction of thermocoagulative injury via use of a picosecond infrared laser
      (PIRL) in laryngeal tissues.
AB  - The carbon dioxide (CO2) laser is routinely used in glottic microsurgery for the
      treatment of benign and malignant disease, despite significant collateral thermal
      damage secondary to photothermal vaporization without thermal confinement.
      Subsequent tissue response to thermal injury involves excess collagen deposition
      resulting in scarring and functional impairment. To minimize collateral thermal
      injury, short-pulse laser systems such as the microsecond pulsed erbium:yttrium
      aluminium-garnet (Er:YAG) laser and picosecond infrared laser (PIRL) have been
      developed. This study compares incisions made in ex vivo human laryngeal tissues
      by CO2 and Er:YAG lasers versus PIRL using light microscopy, environmental
      scanning electron microscopy (ESEM), and infrared thermography (IRT). In
      comparison to the CO2 and Er:YAG lasers, PIRL incisions showed significantly
      decreased mean epithelial (59.70 um) and subepithelial (22.15 um) damage zones (p
      < 0.05). Cutting gaps were significantly narrower for PIRL (133.70 um) compared
      to Er:YAG and CO2 lasers (p < 0.05), which were more than 5 times larger. ESEM
      revealed intact collagen fibers along PIRL cutting edges without obvious
      carbonization, in comparison to diffuse carbonization and tissue melting seen for
      CO2 and Er:YAG laser incisions. IRT demonstrated median temperature rise of 4.1 K
      in PIRL vocal fold incisions, significantly less than for Er:YAG laser cuts
      (171.85 K; p < 0.001). This study has shown increased cutting precision and
      reduced lateral thermal damage zones for PIRL ablation in comparison to
      conventional CO2 and Er:YAG lasers in human glottis and supraglottic tissues. 

PMID- 25575844
TI  - Chronic diseases and life events accounted for 2-18 % population attributable
      risks for adult hearing loss: UK Adult Psychiatric Morbidity Survey, 2007.
AB  - Links between chronic diseases and hearing loss in adults have emerged. However,
      previous investigations were not complete, and the role of life events was
      unclear. Therefore, it was aimed to examine the relationships of common chronic
      diseases and life events and adult hearing loss in a country-wide and population
      based study. Data were retrieved from UK Adult Psychiatric Morbidity Survey,
      2007, being cross-sectional, including demographics, self-reported prior health
      conditions and hearing loss (ever and in the last 12 months), and several major
      life events. Analyses included Chi square test, t test, logistic regression
      model, and population attributable risk estimation. People who had prior health
      conditions including cancer, migraine, dementia, depression, cataracts, chronic
      bronchitis, allergy, bowel problem, bladder problem, arthritis, muscle problem or
      skin problem tended to report hearing loss than their counterparts. People who
      have experienced major life events including post-traumatic stress disorder,
      serious illness of close relatives, death of family, serious problems with
      friends, major financial crisis, valuables stolen, being bullied, violence at
      home, sexual abuse or running away from home were also more likely to experience
      ever hearing loss problem or that in the last 12 months. 2.0-13.1 % adult hearing
      loss could be delayed or prevented by managing chronic diseases while 4.1-18.1 %
      might be delayed or prevented by minimizing the negative effects of life events.
      Chronic diseases and life events were associated with hearing loss in adults.
      Better managing lifestyle to minimize detrimental impacts in future health and
      nursing programs would be suggested.

PMID- 25575845
TI  - Bright spotty lesions on the spinal cord: an additional MRI indicator of
      neuromyelitis optica spectrum disorder?

PMID- 25575846
TI  - A case of variably protease-sensitive prionopathy treated with doxycyclin.

PMID- 25575847
TI  - Performance characteristics of methods for quantifying spontaneous intracerebral
      haemorrhage: data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial.
AB  - BACKGROUND: Poor prognosis after intracerebral haemorrhage (ICH) is related to
      haemorrhage characteristics. Along with developing therapeutic interventions, we
      sought to understand the performance of haemorrhage descriptors in large clinical
      trials. METHODS: Clinical and neuroimaging data were obtained for 548
      participants with ICH from the Efficacy of Nitric Oxide in Stroke (ENOS) trial.
      Independent observers performed visual categorisation of the largest diameter,
      measured volume using ABC/2, modified ABC/2, semiautomated segmentation (SAS),
      fully automatic measurement methods; shape, density and intraventricular
      haemorrhage were also assessed. Intraobserver and interobserver reliability were
      determined for these measures. RESULTS: ICH volume was significantly different
      among standard ABC/2, modified ABC/2 and SAS: (mean) 12.8 (SD 16.3), 8.9 (9.2),
      12.8 (13.1) cm(3), respectively (p<0.0001). There was excellent agreement for
      haemorrhage volume (n=193): ABC/2 intraobserver intraclass correlation
      coefficient (ICC) 0.96-0.97, interobserver ICC 0.88; modified ABC/2 intraobserver
      ICC 0.95-0.97, interobserver ICC 0.91; SAS intraobserver ICC 0.95-0.99,
      interobserver ICC 0.93; largest diameter: (visual) interadjudicator ICC 0.82,
      (visual vs measured) adjudicator vs observer ICC 0.71; shape intraobserver ICC
      0.88 interobserver ICC 0.75; density intraobserver ICC 0.86, interobserver ICC
      0.73. Graeb score (mean 3.53) and modified Graeb (5.22) scores were highly
      correlated. Using modified ABC/2, ICH volume was underestimated in regular (by
      2.2-2.5 cm(3), p<0.0001) and irregular-shaped haemorrhages (by 4.8-4.9 cm(3),
      p<0.0001). Fully automated measurement of haemorrhage volume was possible in only
      5% of cases. CONCLUSIONS: Formal measurement of haemorrhage characteristics and
      visual estimates are reproducible. The standard ABC/2 method is superior to the
      modified ABC/2 method for quantifying ICH volume. CLINICAL TRIAL REGISTRATION:
      ISRCTN9941422.

PMID- 25575849
TI  - Impact of land cover and land use change on runoff characteristics.
AB  - Change in Land Cover and Land Use (LCLU) influences the runoff characteristics of
      a drainage basin to a large extent, which in turn, affects the surface and
      groundwater availability of the area, and hence leads to further change in LCLU.
      This forms a vicious circle. Hence it becomes essential to assess the effect of
      change in LCLU on the runoff characteristics of a region in general and of small
      watershed levels (sub-basin levels) in particular. Such an analysis can
      effectively be carried out by using watershed simulation models with integrated
      GIS frame work. SWAT (Soil and Water Analysis Tool) model, being one of the
      versatile watershed simulation models, is found to be suitable for this purpose
      as many GIS integration modules are available for this model (e.g. ArcSWAT,
      MWSWAT). Watershed simulation using SWAT requires the land use and land cover
      data, soil data and many other features. With the availability of repository of
      satellite imageries, both from Indian and foreign sources, it becomes possible to
      use the concurrent local land use and land cover data, thereby enabling more
      accurate modelling of small watersheds. Such availability will also enable us to
      assess the effect of LCLU on runoff characteristics and their reverse impact. The
      current study assesses the effect of land use and land cover on the runoff
      characteristics of two watersheds in Kerala, India. It also assesses how the
      change in land use and land cover in the last few decades affected the runoff
      characteristics of these watersheds. It is seen that the reduction in the forest
      area amounts to 60% and 32% in the analysed watersheds. However, the changes in
      the surface runoff for these watersheds are not comparable with the changes in
      the forest area but are within 20%. Similarly the maximum (peak) value of runoff
      has increased by an amount of 15% only. The lesser (aforementioned) effect than
      expected might be due to the fact that forest has been converted to agricultural
      purpose with major portion as plantations which have comparatively similar
      characteristics of the forest except for evapo-transpiration. The double sided
      action (increase in evapo-transpiration owing to species like rubber and increase
      percolation due to its plantation method by using terracing) might be the reason
      for relatively smaller effect of the land use change, not commensurate with the
      changes in the forest area amounting to 60% and 32% for Manali and Kurumali
      watersheds respectively. Water harvesting methods like rain harvesting ditches
      can be made mandatory where species with high evapo-transpiration are grown. This
      action shall enhance the groundwater percolation and shall counter act the effect
      due to high evapo-transpiration. 

PMID- 25575848
TI  - Clinical features of hepatocellular carcinoma associated with nonalcoholic fatty
      liver disease: a review of human studies.
AB  - Most cases of hepatocellular carcinoma (HCC) in Japan develop in the background
      of chronic liver disease caused by hepatitis C virus (HCV). Recently, however,
      HCV-associated HCC has been shown to be decreasing, while non-B and non-C HCC
      (NBNC-HCC), which is negative for HCV and hepatitis B virus infection, has
      increased. The main cause of NBNC-HCC is alcoholic liver disease, but the recent
      increase of NBNC-HCC is thought to be due to an increase in patients with
      nonalcoholic fatty liver disease (NAFLD). Approximately 10% of NAFLD cases
      involve nonalcoholic steatohepatitis (NASH), and NASH can progress to liver
      cirrhosis and its associated complications such as HCC. There are no accurate
      data on the percentage of NASH-related HCC among all-cause HCC in Japan, because
      no large-scale investigation has been performed. However, the rate is thought to
      be about 3% of overall HCC, which is lower than that in the United States. The
      incidence of HCC in patients with NASH-related cirrhosis is thought to be 2% per
      year, which is lower than that in HCV-related cirrhosis. Risks for NASH-related
      HCC include advanced hepatic fibrosis, older age, and being male. NAFLD that
      includes NASH is associated with metabolic syndrome, which includes obesity and
      diabetes, and metabolic syndrome is a risk factor for HCC. Genetic factors and
      dietary patterns may also be related to NASH-related HCC. Thus, regular HCC
      surveillance, as performed for patients with viral chronic liver disease, is
      required for patients with NAFLD, and diagnostic markers are required for simple,
      rapid and specific detection of NASH-related HCC.

PMID- 25575850
TI  - N-terminal pro-brain natriuretic peptide and cardiac troponin I for the
      prognostic utility in elderly patients with severe sepsis or septic shock in
      intensive care unit: A retrospective study.
AB  - BACKGROUNDS: Using biomarkers to predict mortality in patient with severe sepsis
      or septic shock is of importance, as these patients frequently have high
      mortality and unsatisfied outcome. N-terminal pro-brain natriuretic peptide (NT
      proBNP) and cardiac troponin I (cTnI) play extremely important roles in
      prognostic value in the mortality of severe sepsis and septic shock. AIMS: The
      present study was retrospectively designed to evaluate the predicting mortality
      of NT-proBNP and cTnI in elderly patients with severe sepsis or septic shock
      administered in the intensive care unit (ICU) and also to evaluate whether the
      predicting ability of Acute Physiology and Chronic Health Evaluation II (APACHE
      II) score or C-reactive protein (CRP) was increased in combination with the
      biomarkers. PATIENTS AND METHODS: A cohort of 430 patients (aged >=65 years) with
      severe sepsis or septic shock admitted to our ICU between October 2011 and
      December 2013 was included in the study. Patient data including clinical,
      laboratory, and survival and mortality were collected. All patients were examined
      with NT-proBNP, cTnI, CRP, and APACHE-II score and were categorized as the
      survived and deceased groups according to the outcome 30 days after ICU
      treatment. RESULTS: The levels of NT-proBNP and cTnI (P < .01) or CRP (P < .05)
      were significantly higher in the deceased group than those in the survived group.
      The predicting mortality of APACHE-II score alone was low but largely improved,
      when it was combined with both NT-proBNP and cTnI (P < .05). CONCLUSION: The
      alteration of NT-proBNP and cTnI levels strongly predicated the ICU prognosis in
      elderly patients with severe sepsis or septic shock. N-terminal pro-brain
      natriuretic peptide and cTnI were superior to CRP in predicting mortality. The
      predicting ability of APACHE-II score was improved only when combined with NT
      proBNP and cTnI.

PMID- 25575851
TI  - Impact of obesity on sepsis mortality: A systematic review.
AB  - PURPOSE: Sepsis and severe sepsis are the most common cause of death among
      critically ill patients admitted in medical intensive care units. As more than
      one-third of the adult population of the United States is obese; we undertook a
      systematic review of the association between obesity and mortality among patients
      admitted with sepsis, severe sepsis, or septic shock. MATERIALS AND METHODS: A
      systematic review was conducted to identify pertinent studies using a
      comprehensive search strategy. Studies reporting mortality in obese patients
      admitted with sepsis were identified. RESULTS: Our initial search identified 183
      studies of which 7 studies met our inclusion criteria. Three studies reported no
      significant association between obesity and mortality, 1 study observed increased
      mortality among obese patients, whereas 3 studies found lower mortality among
      obese patients. CONCLUSION: Our review of the current clinical evidence of
      association of obesity with sepsis mortality revealed mixed results. Clinicians
      are faced with a number of challenges while managing obese patients with sepsis
      and should be mindful of the impact of obesity on antibiotics administration,
      fluid resuscitation, and ventilator management. Further studies are needed to
      elicit the impact of obesity on mortality in patients with sepsis.

PMID- 25575852
TI  - The paracrine effects of adipose-derived stem cells on neovascularization and
      biocompatibility of a macroencapsulation device.
AB  - The foreign-body response to biomaterials compromises the performance of many
      biomedical devices by severe fibrosis and limited neovascularization. Mesenchymal
      stem cells are known to secrete cytokines for treating inflammatory conditions.
      In this study, we aim to investigate whether the paracrine products of adipose
      derived mesenchymal stem cells (ADSCs) can affect the microenvironment of
      biomaterials and improve tissue responses to biomaterial implants. A model system
      was built by loading ADSC spheroids into a macroencapsulation device composed of
      polytetrafluoroethylene (PTFE) filtration membranes. Soluble ADSC factors that
      diffused out of the device in vitro promoted the angiogenetic activity of
      endothelial cells and affected the secretion pattern of macrophages. In vivo
      study was carried out by subcutaneously embedding blank or ADSC-laden devices in
      rats. Following a 4 week implantation, the ADSC-laden devices were better
      vascularized and induced significantly less fibrotic tissue formation in
      comparison to the non-cellular controls. This study may facilitate our
      understanding of foreign-body responses and suggest new ways to improve the
      tissue reaction of biomedical devices for cell-based therapy.

PMID- 25575853
TI  - Myoconductive and osteoinductive free-standing polysaccharide membranes.
AB  - Free-standing (FS) membranes have increasing applications in the biomedical field
      as drug delivery systems for wound healing and tissue engineering. Here, we
      studied the potential of free-standing membranes made by the layer-by-layer
      assembly of chitosan and alginate to be used as a simple biomimetic system of the
      periosteum. The design of a periosteum-like membrane implies the elaboration of a
      thick membrane suitable for both muscle and bone formation. Our aim was to
      produce well-defined ~50 MUm thick polysaccharide membranes that could be easily
      manipulated, were mechanically resistant, and would enable both myogenesis and
      osteogenesis in vitro and in vivo. The membranes were chemically crosslinked to
      improve their mechanical properties. Crosslinking chemistry was followed via
      Fourier transform infrared spectroscopy and the mechanical properties of the
      membranes were assessed using dynamic mechanical analysis. The loading and
      release of the potent osteoinductive growth factor bone morphogenetic protein 2
      (BMP-2) inside and outside of the FS membrane was followed by fluorescence
      spectroscopy in a physiological buffer over 1 month. The myogenic and osteogenic
      potentials of the membranes in vitro were assessed using BMP-2-responsive
      skeletal myoblasts. Finally, their osteoinductive properties in vivo were studied
      in a preliminary experiment using a mouse ectopic model. Our results showed that
      the more crosslinked FS membranes enabled a more efficient myoblast
      differentiation in myotubes. In addition, we showed that a tunable amount of BMP
      2 can be loaded into and subsequently released from the membranes, depending on
      the crosslinking degree and the initial BMP-2 concentration in solution. Only the
      more crosslinked membranes were found to be osteoinductive in vivo. These
      polysaccharide-based membranes have strong potential as a periosteum-mimetic
      scaffold for bone tissue regeneration.

PMID- 25575854
TI  - Drug-loaded bubbles with matched focused ultrasound excitation for concurrent
      blood-brain barrier opening and brain-tumor drug delivery.
AB  - Focused ultrasound (FUS) with microbubbles has been used to achieve local blood
      brain barrier opening (BBB opening) and increase the penetration of therapeutic
      drugs into brain tumors. However, inertial cavitation of microbubbles during FUS
      induced BBB opening causes intracerebral hemorrhaging (ICH), leading to acute and
      chronic brain injury and limiting the efficiency of drug delivery. Here we
      investigated whether induction of drug (1,3-bis(2-chloroethyl)-1-nitrosourea,
      BCNU)-loaded bubbles (BCNU bubbles) to oscillate at their resonant frequency
      would reduce inertial cavitation during BBB opening, thereby eliminating ICH and
      enhancing drug delivery in a rat brain model. FUS was tested at 1 and 10 MHz,
      over a wide range of pressure (mechanical index ranging from 0.16 to 1.42) in the
      presence of BCNU bubbles. Excitation of BCNU bubbles by resonance frequency
      matched FUS (10 MHz) resulted in predominantly stable cavitation and
      significantly reduced the occurrence of potential hazards of exposure to
      biological tissues during the BBB opening process. In addition, the drug release
      process could be monitored by acoustic emission obtained from ultrasound imaging.
      In tumor-bearing animals, BCNU bubbles with FUS showed significant control of
      tumor progression and improved maximum survival from 26 to 35 days. This study
      provides useful advancements toward the goal of successfully translating FUS
      theranostic bubble-enhanced brain drug delivery into clinical use.

PMID- 25575855
TI  - Effect of calcium phosphate coating and rhBMP-2 on bone regeneration in rabbit
      calvaria using poly(propylene fumarate) scaffolds.
AB  - Various calcium phosphate based coatings have been evaluated for better bony
      integration of metallic implants and are currently being investigated to improve
      the surface bioactivity of polymeric scaffolds. The aim of this study was to
      evaluate the role of calcium phosphate coating and simultaneous delivery of
      recombinant human bone morphogenetic protein-2 (rhBMP-2) on the in vivo bone
      regeneration capacity of biodegradable, porous poly(propylene fumarate) (PPF)
      scaffolds. PPF scaffolds were coated with three different calcium phosphate
      formulations: magnesium-substituted beta-tricalcium phosphate (beta-TCMP),
      carbonated hydroxyapatite (synthetic bone mineral, SBM) and biphasic calcium
      phosphate (BCP). In vivo bone regeneration was evaluated by implantation of
      scaffolds in a critical-sized rabbit calvarial defect loaded with different doses
      of rhBMP-2. Our data demonstrated that scaffolds with each of the calcium
      phosphate coatings were capable of sustaining rhBMP-2 release and retained an
      open porous structure. After 6weeks of implantation, micro-computed tomography
      revealed that the rhBMP-2 dose had a significant effect on bone formation within
      the scaffolds and that the SBM-coated scaffolds regenerated significantly greater
      bone than BCP-coated scaffolds. Mechanical testing of the defects also indicated
      restoration of strength in the SBM and beta-TCMP with rhBMP-2 delivery. Histology
      results demonstrated bone growth immediately adjacent to the scaffold surface,
      indicating good osteointegration and osteoconductivity for coated scaffolds. The
      results obtained in this study suggest that the coated scaffold platform
      demonstrated a synergistic effect between calcium phosphate coatings and rhBMP-2
      delivery and may provide a promising platform for the functional restoration of
      large bone defects. 

PMID- 25575856
TI  - Preoperative short-term traction prior to posterior vertebral column resection:
      procedure and role.
AB  - PURPOSE: Severe rigid spine deformity with sharp curve can be effectively
      corrected by posterior vertebral column resection (PVCR). Meanwhile, high risk of
      this procedure also has been recognized generally. The aim of this study is to
      review and evaluate the role of preoperative skull-femoral traction prior to PVCR
      for extremely severe rigid spinal deformity with sharp angular curve >150 degrees
      . METHODS: Twelve cases with extremely severe rigid deformities and sharp curves
      were treated by skull-femoral traction before operation. For them, the mean
      preoperative major scoliotic curve and kyphosis were 153 degrees  (110 degrees 
      168 degrees ) and 109 degrees  (61 degrees -180 degrees ). Continuous skull
      femoral traction in supine position was started 4 weeks before operation. In the
      process of traction, tolerance, neurologic status, deformity changes, etc., were
      reviewed and documented for analysis. PVCR were performed in all these patients
      for final and main correction. RESULTS: The final traction force in the 12 cases
      was 63% of body weight. After 4-week traction, the main scoliotic curve and
      kyphosis were decreased by 34 and 31%. In 1 week, main scoliotic curve and
      kyphosis were decreased by 19 and 15%. In 2 weeks, the major scoliosis curve was
      decreased by 11%, but kyphosis was unexpectedly increased by 4%. Deformity in the
      last 2 weeks was less significant than the first 2 weeks. After PVCR, the main
      scoliotic curve and kyphosis were improved 69 and 66%. No permanent neurological
      damage occurred. CONCLUSION: Preoperative skull-femoral traction effectively
      mitigates the neurological risks of PVCR for extremely severe rigid spinal
      deformity with sharp curve. During traction, scoliosis can be improved more
      significantly and easily than kyphosis.

PMID- 25575857
TI  - Robot-assisted spine surgery: feasibility study through a prospective case
      matched analysis.
AB  - PURPOSE: While image guidance and neuronavigation have enabled a more accurate
      placement of pedicle implants, they can inconvenience the surgeon. Robot-assisted
      placement of pedicle screws appears to overcome these disadvantages. However,
      recent data concerning the superiority of currently available robots in assisting
      spinal surgeons are conflicting. The aim of our study was to evaluate the
      percentage of accurately placed pedicle screws, inserted using a new robotic
      guidance system. METHOD: 20 Patients were operated on successively by the same
      surgeon using robotic assistance (ROSATM, Medtech) (Rosa group 10 patients, n =
      40 screws) or by the freehand conventional technique (Freehand group 10 patients,
      n = 50 screws). Patient characteristics as well as the duration of the operation
      and of exposure to X rays were recorded. RESULTS: The mean age of patients in
      each group (RG and FHG) was 63 years. Mean BMI and operating time among the RG
      and FHG were, respectively, 26 and 27 kg/m(2), and 187 and 119 min. Accurate
      placement of the implant (score A and B of the Gertzbein Robbins classification)
      was achieved in 97.3% of patients in the RG (n = 36) and in 92% of those in the
      FHG (n = 50). Four implants in the RG were placed manually following failed
      robotic assistance. CONCLUSION: We report a higher rate of precision with robotic
      as compared to the FH technique. Providing assistance by permanently monitoring
      the patient's movements, this image-guided tool helps more accurately pinpoint
      the pedicle entry point and control the trajectory. Limitations of the study
      include its small sized and non-randomized sample. Nevertheless, these
      preliminary results are encouraging for the development of new robotic techniques
      for spinal surgery.

PMID- 25575858
TI  - Genetic variation in PBMC-produced IFN-gamma and TNF-alpha associations with
      relapse in multiple sclerosis.
AB  - BACKGROUND: Alterations in peripheral blood mononuclear cell (PBMC) cytokine
      production have been found in multiple sclerosis (MS) compared to healthy
      controls. We have previously found that stimulated PBMC-produced TNF-alpha and
      IFN-gamma modulated MS relapse risk, such that raised TNF-alpha was protective,
      while raised IFN-gamma increased relapse risk. OBJECTIVE: To assess whether SNPs
      within genes for relevant cytokines and their receptors modulate the associations
      of TNF-alpha and IFN-gamma with relapse, thus providing additional information
      about these cytokine effects and the roles of these genes in MS. METHODS:
      Prospective cohort of 91 participants with relapsing-remitting MS and cytokine
      and genotype data. SNPs (N=361) within a window of 10 kb around each
      cytokine/cytokine receptor gene (N=84) were selected for analysis. Predictors of
      PBMC cytokines were evaluated by multilevel mixed-effects linear regression.
      Predictors of relapse were evaluated by Cox proportional hazards regression.
      Bonferroni correction was used to adjust for multiple testing; thus p<1.39 * 10(
      4) was defined as significant. RESULTS: Individuals of GG genotype of rs3218295
      (within the gene IL2RB) demonstrated a significant protective effect of TNF-alpha
      on relapse while those of GA/AA genotype showed a significant positive
      association (pinteraction=5.04 * 10(-5)). Carriers of CC genotype of rs522807 (3'
      region of TNFRSF1B) and the AA genotype of rs25879 (5' region of IL3) showed a
      strong association between IFN-gamma and increased relapse risk
      (pinteraction=8.21 * 10(-5) and 1.70 * 10(-5), respectively). CONCLUSIONS: Our
      results show novel modulation of TNF-alpha and IFN-gamma associations with
      relapse by SNPs in major cytokines. These findings suggest the potential for
      these genes and/or their products as potential therapeutic targets in MS.

PMID- 25575859
TI  - Tumefactive multiple sclerosis and hepatitis C virus 2a/2C infection: Dual
      benefit of long-term interferon beta-1a therapy?
AB  - Hepatitis C virus (HCV) infection has been implicated in triggering acute
      disseminated encephalomyelitis but not tumefactive multiple sclerosis. We report
      the case of a 17-year-old female who presented with a 5-day history of left
      hemiparesis and hemisensory loss followed by a right third nerve palsy.
      Tumefactive multiple sclerosis was diagnosed based on the absence of
      encephalopathic signs, the presence of tumefactive brain lesions, the exclusion
      of neoplastic and infectious causes of the lesions by biopsy, and the occurrence
      of relapse after a period of remission. The patient was at risk for HCV infection
      due to parenteral drug abuse and multiple sexual partners. Serial HCV antibody
      tests and RNA polymerase chain reaction assays revealed acute HCV infection and
      genotyping showed HCV genotype 2a/2c. She was treated with high-dose
      methylprednisolone and discharged with only mild left hand weakness. Interferon
      beta-1a 30mcg was administered intramuscularly once a week. Remission from HCV
      infection was achieved in three years without standard anti-HCV therapy. This
      case suggests that CNS myelin is a potential target of the immune response to HCV
      2a/2c infection, the HCV 2a/2c virus may be involved in triggering autoimmune
      tumefactive brain lesions, and interferon beta-1a is effective against HCV 2a/2c
      infection. We recommend serial HCV antibody testing and HCV RNA PCR assay,
      preferably with HCV genotyping, in all patients with acute inflammatory
      demyelinating diseases of the CNS. 

PMID- 25575860
TI  - The feasibility phase of a community antenatal lifestyle programme [The Lifestyle
      Course (TLC)] for women with a body mass index (BMI)>= 30 kg/m(2.).
AB  - INTRODUCTION: maternal obesity [body mass index (BMI)>=30kg/m(2)] is a cause for
      concern because of increasing rates and risk of associated complications.
      However, little is known about how to improve the health of women with a
      BMI>=30kg/m(2). OBJECTIVE AND METHODS: a 10-week antenatal lifestyle programme
      (The Lifestyle Course - TLC), underpinned by behaviour change theory, was
      developed in a programme of research which included a prospective, multicentred,
      feasibility phase (n=227). Participants had a BMI>=30kg/m(2) at the start of
      their pregnancy, planned to deliver in two areas of Greater Manchester and were
      aged 18 or over. The objectives were to (1) assess the feasibility of the
      intervention and (2) to pilot the trial processes and outcome measures. FINDINGS:
      (1) Trial intervention: only 22% of women in the feasibility phase had received
      gestational weight advice prior to the study. One or more TLC sessions were
      attended by 79% of women and 97% said they would recommend TLC to a friend due to
      the content suitability, perceived personal gains and extra care received.
      Changes to the TLC were suggested and implemented in the pilot phase. (2) Trial
      processes: recruitment rates (36%), retention rates (100%) and questionnaire
      completion rates up to one year (33%) were found. Daily general 'lifestyle'
      diaries and pedometers were not acceptable data collection tools (response rates
      of 32% and 16% respectively). However, specific food diaries were acceptable
      (response rates of 80-81%). The major challenge was the collection of maternal
      weight data at the follow-up points. CONCLUSIONS AND IMPLICATIONS: the antenatal
      intervention (TLC) designed for this programme of work appears to suit the needs
      of women with a BMI>=30kg/m(2). The need for an antenatal intervention is clear
      from this study and also highlights reflections on effective communication with
      pregnant women with a BMI>=30kg/m(2). Lessons learnt for designing a future trial
      include effective ways to communicate with pregnant women with a BMI>=30kg/m(2).
      TRIAL REGISTRATION: ISRCTN29860479.

PMID- 25575861
TI  - Female genital mutilation: knowledge, attitude and practices of Flemish midwives.
AB  - BACKGROUND: health professionals in Belgium are confronted with female genital
      mutilation (FGM). To date, no survey to assess knowledge, attitudes and practices
      on FGM was conducted among midwives in the Northern region of Belgium. OBJECTIVE:
      the objective of this study was to assess the knowledge, attitude and practices
      of Flemish midwives regarding female genital mutilation (FGM). DESIGN: we used a
      quantitative design, using KAP study (semi-structured questionnaire). SETTING:
      labour wards, maternity wards and maternal intensive care units (MIC) in 56
      hospitals in Flemish region of Belgium. PARTICIPANTS: 820 midwives, actively
      working in labour wards, maternity wards and maternal intensive care units (MIC).
      FINDINGS: 820 valid questionnaires (40.9%) were returned. More than 15% of the
      respondents were recently confronted with FGM. They were mostly faced with the
      psychological and sexual complications caused by FGM. Few respondents were aware
      of existing guidelines regarding FGM in their hospitals (3.5%). The results also
      showed that only 20.2% was aware of the exact content of the law. The majority of
      midwives condemned the harmful traditional practice: FGM was experienced as a
      form of violence against women or a violation of human rights. Only 25.9%
      declared that FGM forms a part of their midwifery program. The vast majority of
      respondents (92.5%) indicated a need for more information on the subject. KEY
      CONCLUSIONS: this study indicated that midwives in Flanders are confronted with
      FGM and its complications and highlighted the gaps in the knowledge of Flemish
      midwives regarding FGM. This may interfere with the provision of adequate care
      and prevention of FGM for the new-born daughter. IMPLICATIONS FOR PRACTICE: there
      is an important need for appropriate training of (student)midwives concerning FGM
      as well as for the development and dissemination of clear guidelines in Flemish
      hospitals.

PMID- 25575862
TI  - The NHS lacks cardiovascular screening tools suitable for patients of South Asian
      descent.

PMID- 25575863
TI  - A spatio-temporal cardiomyocyte targeted vector system for efficient delivery of
      therapeutic payloads to regress cardiac hypertrophy abating bystander effect.
AB  - Diverse array of therapeutic regimens, drugs or siRNA, are commonly used to
      regress cardiac hypertrophy, although, bystander effect and lower retention of
      bioactive molecules significantly reduce their functional clinical efficacy.
      Carvedilol, a widely used and effective anti-hypertrophic drug, simultaneously
      blocks beta-adrenergic receptors non-specifically in various organs. Likewise,
      non-specific genome-wide downregulation of p53 expression by specific siRNA
      efficiently abrogates cardiac hypertrophy but results in extensive tumorigenesis
      affecting bystander organs. Therefore, delivery of such therapeutics had been a
      challenge in treating cardiovascular dysfunction. Cardiac tissue engineering was
      successfully accomplished in this study, by encapsulating such bioactive
      molecules with a stearic acid modified Carboxymethyl chitosan (CMC) nanopolymer
      conjugated to a homing peptide for delivery to hypertrophied cardiomyocytes in
      vivo. The peptide precisely targeted cardiomyocytes while CMC served as the
      vector mediator to pathological myocardium. Controlled delivery of active
      therapeutic payloads within cardiomyocytes resulted in effective regression of
      cardiac hypertrophy. Thus, this novel nano-construct as a spatio-temporal vector
      would be a potential tool for developing effective therapeutic strategies within
      cardiac micro-environment via targeted knockdown of causal genes. 

PMID- 25575864
TI  - Delivery of bortezomib with nanoparticles for basal-like triple-negative breast
      cancer therapy.
AB  - Basal-like triple negative breast cancer (TNBC) has received particular clinical
      interest due to its high frequency, poor baseline prognosis and lack of effective
      clinical therapy. Bortezomib, which was the first proteasome inhibitor approved
      for the treatment of multiple myeloma, has been proven to be worth investigating
      for this subtype of breast cancer. In our study, the amphiphilic copolymer
      poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-b-PLA) was utilized as an
      excellent delivery carrier of bortezomib (BTZ) to overcome its clinical
      limitations including low water solubility and unstable properties. Bortezomib
      encapsulated nanoparticles (NPBTZ) can efficiently deliver the drug into both
      CSCs (cancer stem cells) and non-CSCs, resulting in proliferation inhibition and
      apoptosis induction. Remarkably, NPBTZ can more effectively affect the stemness
      of CSCs compared with free BTZ. Administration of this drug delivery system can
      markedly prolong the bortezomib circulation half-life and augment the enrichment
      of drugs in tumor tissue, then enhance the suppression of tumor growth,
      suggesting the therapeutic promise of NPBTZ delivery in basal-like TNBC therapy.

PMID- 25575865
TI  - pH-sensitive oncolytic adenovirus hybrid targeting acidic tumor microenvironment
      and angiogenesis.
AB  - Although oncolytic adenoviruses (Ads) are an attractive option for cancer gene
      therapy, the intravenous administration of naked Ad still encounters unfavorable
      host responses, non-specific interactions, and heterogeneity in targeted cancer
      cells. To overcome these obstacles and achieve specific targeting of the tumor
      microenvironment, Ad was coated with the pH-sensitive block copolymer, methoxy
      poly(ethylene glycol)-b-poly(l-histidine-co-l-phenylalanine) (PEGbPHF). The
      physicochemical properties of the generated nanocomplex, Ad/PEGbPHF, were
      assessed. At pH6.4, GFP-expressing Ad/PEGbPHF induced significantly higher GFP
      expression than naked Ad in both coxsackie and adenovirus receptor (CAR)-positive
      and -negative cells. To assess the therapeutic efficacy of the Ad/PEGbPHF complex
      platform, an oncolytic Ad expressing VEGF promoter-targeting transcriptional
      repressor (KOX) was used to form complexes. At pH6.4, KOX/PEGbPHF significantly
      suppressed VEGF gene expression, cancer cell migration, vessel sprouting, and
      cancer cell killing effect compared to naked KOX or KOX/PEGbPHF at pH7.4,
      demonstrating that KOX/PEGbPHF can overcome the lack of CAR that is frequently
      observed in tumor tissues. The antitumor activity of KOX/PEGbPHF systemically
      administered to a tumor xenograft model was significantly higher than that of
      naked KOX. Furthermore, KOX/PEGbPHF showed lower hepatic toxicity and did not
      induce an innate immune response against Ad. Altogether, these results
      demonstrate that pH-sensitive polymer-coated Ad complex significantly increases
      net positive charge upon exposure to hypoxic tumor microenvironment, allowing
      passive targeting to the tumor tissue. It may offer superior potential for
      systemic therapy, due to its improved tumor selectivity, increased therapeutic
      efficacy, and lower toxicity compared to naked KOX. 

PMID- 25575866
TI  - Development of porous PLGA/PEI1.8k biodegradable microspheres for the delivery of
      mesenchymal stem cells (MSCs).
AB  - Multipotent mesenchymal stem cells (MSCs) promise a therapeutic alternative for
      many debilitating and incurable diseases. However, one of the major limitations
      for the therapeutic application of human MSC (hMSC) is the lengthy ex vivo
      expansion time for preparing a sufficient amount of cells due to the low
      engraftment rate after transplantation. To solve this conundrum, a porous
      biodegradable polymeric microsphere was investigated as a potential scaffold for
      the delivery of MSCs. The modified water/oil/water (W1/O/W2) double emulsion
      solvent evaporation method was used for the construction of porous microspheres.
      PEI1.8k was blended with poly(lactic-co-glycolic acid) (PLGA) to enhance
      electrostatic cellular attachment to the microspheres. The porous PLGA/PEI1.8k
      (PPP) particles demonstrated an average particle size of 290MUm and an average
      pore size of 14.3MUm, providing a micro-carrier for the MSC delivery. PPP
      particles allowed for better attachment of rMSCs than non-porous PLGA/PEI1.8k
      (NPP) particles and non-porous (NP) and porous PLGA (PP) microspheres. rMSC
      successfully grew on the PPP particles for 2weeks in vitro. Next, PPP particles
      loaded with 3 different amounts of hMSC showed increased in vivo engraftment
      rates and maintained the stemness characteristics of hMSC compared with hMSCs
      alone group in rats 2weeks after intramyocardial administration. These customized
      PPP particles for MSC delivery are a biodegradable and injectable scaffold that
      can be used for clinical applications. 

PMID- 25575868
TI  - Dentomaxillofacial imaging with panoramic views and cone beam CT.
AB  - Panoramic and intraoral radiographs are the basic imaging modalities used in
      dentistry. Often they are the only imaging techniques required for delineation of
      dental anatomy or pathology. Panoramic radiography produces a single image of the
      maxilla, mandible, teeth, temporomandibular joints and maxillary sinuses. During
      the exposure the x-ray source and detector rotate synchronously around the
      patient producing a curved surface tomography. It can be supplemented with
      intraoral radiographs. However, these techniques give only a two-dimensional view
      of complicated three-dimensional (3D) structures. As in the other fields of
      imaging also dentomaxillofacial imaging has moved towards 3D imaging. Since the
      late 1990s cone beam computed tomography (CBCT) devices have been designed
      specifically for dentomaxillofacial imaging, allowing accurate 3D imaging of hard
      tissues with a lower radiation dose, lower cost and easier availability for
      dentists when compared with multislice CT. Panoramic and intraoral radiographies
      are still the basic imaging methods in dentistry. CBCT should be used in more
      demanding cases. In this review the anatomy with the panoramic view will be
      presented as well as the benefits of the CBCT technique in comparison to the
      panoramic technique with some examples. Also the basics as well as common errors
      and pitfalls of these techniques will be discussed. Teaching Points * Panoramic
      and intraoral radiographs are the basic imaging methods in dentomaxillofacial
      radiology.* CBCT imaging allows accurate 3D imaging of hard tissues.* CBCT offers
      lower costs and a smaller size and radiation dose compared with MSCT.* The
      disadvantages of CBCT imaging are poor soft tissue contrast and artefacts.* The
      Sedentexct project has developed evidence-based guidelines on the use of CBCT in
      dentistry. 

PMID- 25575867
TI  - Genetically engineered theranostic mesenchymal stem cells for the evaluation of
      the anticancer efficacy of enzyme/prodrug systems.
AB  - Over the past decade, various enzyme/prodrug systems such as thymidine
      kinase/ganciclovir (TK/GCV), yeast cytosine deaminase/5-fluorocytosine (yCD/5-FC)
      and nitroreductase/CB1954 (NTR/CB1954) have been used for stem cell mediated
      suicide gene therapy of cancer. Yet, no study has been conducted to compare and
      demonstrate the advantages and disadvantages of using one system over another.
      Knowing that each enzyme/prodrug system has its own strengths and weaknesses, we
      utilized mesenchymal stem cells (MSCs) as a medium to perform for the first time
      a comparative study that illustrated the impact of subtle differences among these
      systems on the therapeutic outcome. For therapeutic purposes, we first
      genetically modified MSCs to stably express a panel of four suicide genes
      including TK (TK007 and TK(SR39) mutants), yeast cytosine deaminase:uracil
      phosphoribosyltransferase (yCD:UPRT) and nitroreductase (NTR). Then, we evaluated
      the anticancer efficacies of the genetically engineered MSCs in vitro and in vivo
      by using SKOV3 cell line which is sensitive to all four enzyme/prodrug systems.
      In addition, all MSCs were engineered to stably express luciferase gene making
      them suitable for quantitative imaging and dose-response relationship studies in
      animals. Considering the limitations imposed by the prodrugs' bystander effects,
      our findings show that yCD:UPRT/5-FC is the most effective enzyme/prodrug system
      among the ones tested. Our findings also demonstrate that theranostic MSCs are a
      reliable medium for the side-by-side evaluation and screening of the
      enzyme/prodrug systems at the preclinical level. The results of this study could
      help scientists who utilize cell-based, non-viral or viral vectors for suicide
      gene therapy of cancer make more informed decisions when choosing enzyme/prodrug
      systems.

PMID- 25575869
TI  - Levels and sources of PCDDs, PCDFs and dl-PCBs in the water ecosystems of central
      Poland - a mini review.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are unwanted
      by-products in a variety of industrial and thermal processes. They have been
      present on Earth long before the human era, since they may be also formed as a
      result of forest fires or volcanic explosions. Polychlorinated biphenyls (PCBs)
      in turn, have been intentionally produced by humans. Poland was a minor producer
      of PCB mixtures (Chlorofen and Tarnol), which were a source of direct and
      indirect environmental diffusion with PCB and less with PCDDs/PCDFs. Industrial
      accidents with PCDDs/PCDFs were absent in Poland. Their stability and resistance
      to thermal breakdown made them very dangerous for environment and, in
      consequence, due to their environmental persistence, bioaccumulation and
      biomagnification in the terrestrial and aquatic food chains, to humans. Humans
      may become affected by PCDDs/PCDFs and PCBs through environmental (soil and water
      contamination, fish and food), occupational (incinerators; pulp, paper and
      metallurgy industry; copper production), or accidental (Seveso accident)
      exposure. The aim of this review was to evaluate environmental hazard caused by
      PCDDs, PCDFs and dioxin-like-PCBs in the central region of Poland based on the
      accessible data on diffusion of those compounds in sediments and riverine,
      reservoir and storm water from our previous studies and discussed in the context
      of other achievements in Poland and elsewhere. 

PMID- 25575870
TI  - Can less be more? Comparison of an 8-item placement quality measure with the 50
      item Dundee Ready Educational Environment Measure (DREEM).
AB  - Clinical clerks learn more than they are taught and not all they learn can be
      measured. As a result, curriculum leaders evaluate clinical educational
      environments. The quantitative Dundee Ready Environment Measure (DREEM) is a de
      facto standard for that purpose. Its 50 items and 5 subscales were developed by
      consensus. Reasoning that an instrument would perform best if it were underpinned
      by a clearly conceptualized link between environment and learning as well as
      psychometric evidence, we developed the mixed methods Manchester Clinical
      Placement Index (MCPI), eliminated redundant items, and published validity
      evidence for its 8 item and 2 subscale structure. Here, we set out to compare
      MCPI with DREEM. 104 students on full-time clinical placements completed both
      measures three times during a single academic year. There was good agreement and
      at least as good discrimination between placements with the smaller MCPI. Total
      MCPI scores and the mean score of its 5-item learning environment subscale
      allowed ten raters to distinguish between the quality of educational
      environments. Twenty raters were needed for the 3-item MCPI training subscale and
      the DREEM scale and its subscales. MCPI compares favourably with DREEM in that
      one-sixth the number of items perform at least as well psychometrically, it
      provides formative free text data, and it is founded on the widely shared
      assumption that communities of practice make good learning environments. 

PMID- 25575871
TI  - Regulatory focus in predictions about others.
AB  - Based on social projection research, four studies investigated whether people
      rely on their own regulatory focus when making predictions about others. Chronic
      (Study 1) and induced (Study 2) regulatory focus shaped estimations of others'
      strategic promotion or prevention inclinations and choices between enriched
      (fitting promotion) and impoverished options (fitting prevention). Providing
      indirect process evidence via boundary conditions, participants only relied on
      their induced regulatory focus in predictions of others' inclinations to seek
      romantic alternatives to the extent that this did not run counter to stereotypic
      gender beliefs (Study 3). In addition, participants only relied on their induced
      regulatory focus in preference predictions concerning promotion and prevention
      products when they lacked idiosyncratic target knowledge (Study 4). These effects
      were not mediated by mood, judgment-certainty, perceived task-enjoyment, or task
      difficulty. Implications of these findings for social projection research as well
      as possible interpersonal consequences are delineated. 

PMID- 25575872
TI  - The different behavioral intentions of collectivists and individualists in
      response to social exclusion.
AB  - We investigated how participants with collectivistic and individualistic
      orientation cope with social exclusion on a behavioral level. In Studies 1 and 2,
      we found participants with more individualistic orientation to indicate more
      antisocial behavioral intentions in response to exclusion than in response to
      inclusion; however, participants with more collectivistic orientation did not
      differ in their behavioral intentions between exclusion and inclusion. In the
      third and fourth study, we replicated our findings across cultures: German and
      U.S. participants indicated more antisocial and avoiding behavioral intentions
      under exclusion than under inclusion, whereas Turkish and Indian participants did
      not differ in their behavioral intentions between exclusion and inclusion. In
      Studies 3 and 4, only German and U.S. participants were significantly affected by
      exclusion, showing more negative mood, which correlated with their behavioral
      intentions. In Study 4, the different behavioral intentions of collectivists and
      individualists were mediated by a different threat experience. The findings
      emphasize the role of self-construal and culture, as well as the self-threat
      inherent in exclusion. 

PMID- 25575873
TI  - Prevalence and risk factors of inadequate cervical dilation following laminaria
      insertion in second-trimester abortion--case control study.
AB  - OBJECTIVE: The objective was to explore the prevalence of and risk factors for
      inadequate cervical dilation following insertion of a single set of laminaria in
      women scheduled for dilation & evacuation (D&E) at 14-24 weeks' gestation. STUDY
      DESIGN: We retrospectively reviewed all cases of women who underwent pregnancy
      termination by D&E at 14-24 weeks' gestation between January 2003 and December
      2013. All cases in which the surgical procedure was cancelled due to failure to
      achieve adequate cervical dilation after a single set of laminaria inadequate
      cervical dilation were included. The control group was women who underwent D&E
      following adequate cervical dilation after a single set of laminaria, and were
      matched according to gestational week in a ratio of 1:3. RESULTS: The overall
      dilation failure rate was 3.2%, with 4.0% among the induced-abortion patients and
      1.5% among the patients with fetal demise (p=.002). Patients who had inadequate
      cervical dilation had lower rates of gravidity (p=.002) and previous spontaneous
      vaginal delivery (p<.001), along with higher rates of primigravidity, nulliparity
      (p<.001), previous cesarean section/s (p=.041), previous abdominal surgeries
      (p=.001) and previous cervical procedures (p=.003), compared to controls. A
      multivariable logistic regression analysis revealed two risk factors for
      inadequate cervical dilation following laminaria insertion, namely, previous
      cesarean section (p=.002) and previous cervical procedure (p<.001), whereas
      increased gravidity was found to protect against inadequate cervical dilation
      (p=.002). CONCLUSIONS: Previous cesarean section/s, cervical procedures and
      primigravidity were found to be risk factors for failure to achieve adequate
      cervical dilation after a single set of laminaria. Women who are scheduled for
      D&E, and in whom one of these risk factors exists, might benefit from additional
      interventions to achieve better cervical preparation.

PMID- 25575874
TI  - Pilot test of the Healthy Food Environment Policy Index (Food-EPI) to increase
      government actions for creating healthy food environments.
AB  - OBJECTIVES: Effective government policies are essential to increase the
      healthiness of food environments. The International Network for Food and
      Obesity/non-communicable diseases (NCDs) Research, Monitoring and Action Support
      (INFORMAS) has developed a monitoring tool (the Healthy Food Environment Policy
      Index (Food-EPI)) and process to rate government policies to create healthy food
      environments against international best practice. The aims of this study were to
      pilot test the Food-EPI, and revise the tool and process for international
      implementation. SETTING: New Zealand. PARTICIPANTS: Thirty-nine informed,
      independent public health experts and non-governmental organisation (NGO)
      representatives. PRIMARY AND SECONDARY OUTCOME MEASURES: Evidence on the extent
      of government implementation of different policies on food environments and
      infrastructure support was collected in New Zealand and validated with government
      officials. Two whole-day workshops were convened of public health experts and NGO
      representatives who rated performance of their government for seven policy and
      seven infrastructure support domains against international best practice. In
      addition, the raters evaluated the level of difficulty of rating, and
      appropriateness and completeness of the evidence presented for each indicator.
      RESULTS: Inter-rater reliability was 0.85 (95% CI 0.81 to 0.88; Gwet's AC2) using
      quadratic weights, and increased to 0.89 (95% CI 0.85 to 0.92) after deletion of
      the problematic indicators. Based on raters' assessments and comments, major
      changes to the Food-EPI tool include strengthening the leadership domain,
      removing the workforce development domain, a stronger focus on equity, and adding
      community-based programmes and government funding for research on obesity and
      diet-related NCD prevention, as good practice indicators. CONCLUSIONS: The
      resulting tool and process will be promoted and offered to countries of varying
      size and income globally. International benchmarking of the extent of government
      policy implementation on food environments has the potential to catalyse greater
      government action to reduce obesity and NCDs, and increase civil society's
      capacity to advocate for healthy food environments.

PMID- 25575875
TI  - Protocol for the surgical and large bore procedures in malignant pleural
      mesothelioma and radiotherapy trial (SMART Trial): an RCT evaluating whether
      prophylactic radiotherapy reduces the incidence of procedure tract metastases.
AB  - INTRODUCTION: Patients with malignant pleural mesothelioma (MPM) may develop
      painful 'procedure tract metastasis' (PTM) at the site of previous pleural
      interventions. Prophylactic radiotherapy has been used to minimise this
      complication; however, three small randomised trials have shown conflicting
      results regarding its effectiveness. The surgical and large bore procedures in
      malignant pleural mesothelioma and radiotherapy trial (SMART Trial) is a suitably
      powered, multicentre, randomised controlled trial, designed to evaluate the
      efficacy of prophylactic radiotherapy within 42 days of pleural instrumentation
      in preventing the development of PTM in MPM. METHODS AND ANALYSIS: 203 patients
      with a histocytologically proven diagnosis of MPM, who have undergone a large
      bore pleural intervention (thoracic surgery, large bore chest drain, indwelling
      pleural catheter or local anaesthetic thoracoscopy) in the previous 35 days, will
      be recruited from UK hospitals. Patients will be randomised (1:1) to receive
      immediate radiotherapy (21 Gy in 3 fractions over 3 working days within 42 days
      of the pleural intervention) or deferred radiotherapy (21 Gy in 3 fractions over
      3 working days given if a PTM develops). Patients will be followed up for 12
      months. The primary outcome measure is the rate of PTM until death or 12 months
      (whichever is sooner), as defined by the presence of a clinically palpable nodule
      of at least 1 cm diameter felt within 7 cm of the margins of the procedure site
      as confirmed by two assessors. Secondary outcome measures include chest pain,
      quality of life, analgaesic requirements, healthcare utilisation and safety
      (including radiotherapy toxicity). ETHICS AND DISSEMINATION: The trial has
      received ethical approval from the Southampton B Research Ethics Committee
      (11/SC/0408). There is a Trial Steering Committee, including independent members
      and a patient and public representative. The trial results will be published in a
      peer-reviewed journal and presented at international conferences. TRIAL
      REGISTRATION NUMBER: ISRCTN72767336.

PMID- 25575876
TI  - A short-term risk-benefit analysis of occasional and regular use of low-dose
      aspirin in primary prevention of vascular diseases: a nationwide population-based
      study.
AB  - OBJECTIVE: To calculate the short-term risk-benefit effect of occasional and
      regular use of low-dose aspirin (<=100 mg/day) in primary prevention. STUDY
      DESIGN: Two retrospective cohort studies. SETTING: Taiwan. PARTICIPANTS: 63 788
      and 24 910 patients of two nationwide population-based studies were examined.
      METHODS: Two databases of 1 000 000 patients were randomly sampled from data of
      Taiwan's National Health Insurance (NHI) for years 1997-2000 (NHI 2000) and 2005
      (NHI 2005). In NHI 2000, 63 788 patients 30-95 years of age were found not to
      have previously been prescribed aspirin before 1 January 2000, but to have first
      been prescribed low-dose aspirin after that date. They were also found to be at
      risk of first hospitalisation for any major vascular diseases including
      haemorrhage (major gastrointestinal haemorrhage or cerebral haemorrhage) and
      ischaemia (acute myocardial infarction or ischaemic stroke) after their first
      prescription. We also applied it to NHI 2005, and the number of eligible patients
      was 24 910. Patients prescribed low-dose aspirin for <20% of the days of a 60-day
      follow-up period were considered to be occasional users, and those prescribed low
      dose aspirin for >=80% of the days were considered to be regular users.
      Differences in rate of haemorrhage and ischaemia between these users were used to
      calculate their net clinical risk. PRIMARY OUTCOME: Vascular diseases. RESULTS:
      In NHI 2000, the overall unadjusted rates of haemorrhage and ischaemia were 0.09%
      and 0.21%, respectively, for occasional users and 0.32% and 2.30%, respectively,
      for regular users. Adjusted net clinical risk of low-dose aspirin use between the
      two groups was 2.24% (95% CI 2.03% to 2.48%; p<0.001). Similar results were also
      found in NHI 2005. CONCLUSIONS: Short-term regular use of low-dose aspirin might
      not be better than occasional use for preventing major vascular diseases in
      primary prevention. Prescribing regular low-dose aspirin for primary prevention
      should be done with caution. Future studies should explore the risk-benefit
      effect of long-term low-dose aspirin use in primary prevention.

PMID- 25575877
TI  - Novel reassortant H5N5 viruses bind to a human-type receptor as a factor in
      pandemic risk.
AB  - Highly pathogenic avian influenza A(HPAI) H5N1 viruses pose a serious pandemic
      threat due to their virulence and high mortality in humans, and their
      increasingly expanding host range and significant ongoing evolution could enhance
      their human-to-human transmissibility. Recently, various reassortant viruses were
      detected in different domestic poultry, with the HA gene derived from the
      A/goose/Guangdong/1/96-like (Gs/GD-like) lineage and the NA gene from influenza
      viruses of other subtypes. It is reported that some natural reassortant H5N5
      highly pathogenic avian influenza viruses were isolated from poultry in China.
      And their HA genes were belonged to a new clade 2.3.4.4. We evaluated the
      receptor binding property and transmissibility in guinea pigs of these
      reassortant H5N5 HPAIVs. The results showed that these viruses bound to both
      avian-type (alpha-2,3) and human-type (alpha-2,6) receptors. In addition, we
      found that one of these viruses, 031, not only replicated but also transmitted
      efficiently in guinea pigs. Therefore, such reassortant influenza viruses may
      pose a pandemic threat. 

PMID- 25575878
TI  - Identification of a novel herpesvirus in captive Eastern box turtles (Terrapene
      carolina carolina).
AB  - Herpesviruses are significant pathogens of chelonians which most commonly cause
      upper respiratory tract disease and necrotizing stomatitis. Herpesvirus infection
      was identified in two populations of captive Eastern box turtles (Terrapene
      carolina carolina) using histopathology and polymerase chain reaction (PCR) with
      DNA sequencing. Necrotizing lesions with eosinophilic to amphophilic intranuclear
      inclusion bodies were identified in the tissues of one hatch-year individual in
      January 2013, which was herpesvirus positive by PCR. A separate captive group of
      adults had an observed herpesvirus prevalence of 58% using PCR in July 2011. In
      these cases, a novel herpesvirus, Terrapene herpesvirus 1 (TerHV1), was
      identified and serves as the first herpesvirus sequenced in the genus Terrapene.
      Similar to the other herpesviruses of the Order Testudines, TerHV1 clusters with
      the genus Scutavirus of the subfamily Alphaherpesvirinae. 

PMID- 25575879
TI  - Mycoplasma gallisepticum in vivo induced antigens expressed during infection in
      chickens.
AB  - Until now only a few genes encoding virulence factors have been characterized in
      the avian pathogen Mycoplasma gallisepticum. In order to identify candidate
      targets associated with infection we applied an immunoscreening technique-in vivo
      induced antigen technology (IVIAT)-to detect immunogens of M. gallisepticum
      strain Rlow expressed preferentially during in vivo infection. We identified 13
      in vivo-induced (IVI) proteins that correspond to different functional categories
      including: previously reported putative virulence factors (GapA, PlpA, Hlp3, VlhA
      1.07 and VlhA 4.01), transport (PotE, MGA_0241 and 0654), translation (L2, L23,
      ValS), chaperone (GroEL) and a protein with unknown function (MGA_0042). To
      validate the in vivo antigenic reactivity, 10 IVI proteins were tested by Western
      blot analysis using serum samples collected from chickens experimentally (with
      strain Rlow) and naturally (outbreaks, N=3) infected with M. gallisepticum. All
      IVI proteins tested were immunogenic. To corroborate these results, we tested
      expression of IVI genes in chickens experimentally infected with M. gallisepticum
      Rlow, and in MRC-5 human lung fibroblasts cell culture by using relative real
      time reverse-transcription PCR (RT-PCR). With the exception of MGA_0338, all six
      genes tested (MGA_1199, 0042, 0654, 0712, 0928 and 0241) were upregulated at
      least at one time point during experimental infection (2-4 week post-infection).
      In contrast, the expression of seven out of eight IVI genes (MGA_1199, 0152,
      0338, 0042, 0654, 0712, 0928) were downregulated in MRC-5 cell culture at both 2
      and 4h PI; MGA_0241 was upregulated 2h PI. Our data suggest that the identified
      IVI antigens may have important roles in the pathogenesis of M. gallisepticum
      infection in vivo. 

PMID- 25575880
TI  - Serological evidence of avian influenza virus and canine influenza virus
      infections among stray cats in live poultry markets, China.
AB  - From January 2010 to January 2012, we collected sera samples from 700 stray cats
      living in close proximity to poultry farms or poultry markets in 4 provinces in
      China. A number of cats had evidence of avian and canine influenza virus
      infection: avian H9N2 [24 by HI >=1:20 and 16 by microneutralization (MN) assay
      >=1:80]; avian H5N1 (9 by HI >=1:20 and 3 by MN assay >=1:80) and canine H3N2 (32
      by HI >=1:20 and 18 by MN >=1:80). Bivariate analyses revealed that cats sampled
      near live poultry markets and cats with influenza-like-illness were at increased
      risk of having elevated antibody titers by HI against avian H9N2, avian H5N1, or
      canine H3N2 viruses. Hence, cats may play a very important role in the ecology of
      novel influenza viruses and periodic epidemiological surveillance for novel
      influenza infections among stray cats could serve as an early warning system for
      human threats. 

PMID- 25575881
TI  - Functional connectivity pattern during rest within the episodic memory network in
      association with episodic memory performance in bipolar disorder.
AB  - In this study, we sought to examine the intrinsic functional organization of the
      episodic memory network during rest in bipolar disorder (BD). The previous work
      suggests that deficits in intrinsic functional connectivity may account for
      impaired memory performance. We hypothesized that regions involved in episodic
      memory processing would reveal aberrant functional connectivity in patients with
      bipolar disorder. We examined 21 patients with BD and 21 healthy matched controls
      who underwent functional magnetic resonance imaging (fMRI) during a resting
      condition. We did a seed-based functional connectivity analysis (SBA), using the
      regions of the episodic memory network that showed a significantly different
      activation pattern during task-related fMRI as seeds. The functional connectivity
      scores (FC) were further correlated with episodic memory task performance. Our
      results revealed decreased FC scores within frontal areas and between frontal and
      temporal/hippocampal/limbic regions in BD patients in comparison with controls.
      We observed higher FC in BD patients compared with controls between frontal and
      limbic regions. The decrease in fronto-frontal functional connectivity in BD
      patients showed a significant positive association with episodic memory
      performance. The association between task-independent dysfunctional frontal
      limbic FC and episodic memory performance may be relevant for current
      pathophysiological models of the disease. 

PMID- 25575883
TI  - Neuron-derived orphan receptor 1: working towards a common goal.

PMID- 25575882
TI  - Role of phosphoinositide 3-kinase IA (PI3K-IA) activation in cardioprotection
      induced by ouabain preconditioning.
AB  - Acute myocardial infarction, the clinical manifestation of ischemia-reperfusion
      (IR) injury, is a leading cause of death worldwide. Like ischemic preconditioning
      (IPC) induced by brief episodes of ischemia and reperfusion, ouabain
      preconditioning (OPC) mediated by Na/K-ATPase signaling protects the heart
      against IR injury. Class I PI3K activation is required for IPC, but its role in
      OPC has not been investigated. While PI3K-IB is critical to IPC, studies have
      suggested that ouabain signaling is PI3K-IA-specific. Hence, a pharmacological
      approach was used to test the hypothesis that OPC and IPC rely on distinct PI3K-I
      isoforms. In Langendorff-perfused mouse hearts, OPC was initiated by 4 min of
      ouabain 10 MUM and IPC was triggered by 4 cycles of 5 min ischemia and
      reperfusion prior to 40 min of global ischemia and 30 min of reperfusion. Without
      affecting PI3K-IB, ouabain doubled PI3K-IA activity and Akt phosphorylation at
      Ser(473). IPC and OPC significantly preserved cardiac contractile function and
      tissue viability as evidenced by left ventricular developed pressure and end
      diastolic pressure recovery, reduced lactate dehydrogenase release, and decreased
      infarct size. OPC protection was blunted by the PI3K-IA inhibitor PI-103, but not
      by the PI3K-IB inhibitor AS-604850. In contrast, IPC-mediated protection was not
      affected by PI-103 but was blocked by AS-604850, suggesting that PI3K-IA
      activation is required for OPC while PI3K-IB activation is needed for IPC.
      Mechanistically, PI3K-IA activity is required for ouabain-induced Akt activation
      but not PKCepsilon translocation. However, in contrast to PKCepsilon
      translocation which is critical to protection, Akt activity was not required for
      OPC. Further studies shall reveal the identity of the downstream targets of this
      new PI3K IA-dependent branch of OPC. These findings may be of clinical relevance
      in patients at risk for myocardial infarction with underlying diseases and/or
      medication that could differentially affect the integrity of cardiac PI3K-IA and
      IB pathways.

PMID- 25575884
TI  - Does wearing shoes affect your biomechanical efficiency?
AB  - Studies involving minimalist shoes have dramatically increased this past 10
      years. While a deeper knowledge of the related modifications has ensued regarding
      the kinematics, electromyographic, and dynamic patterns, little is known
      regarding the modifications at the muscle forces and muscle fiber levels. The aim
      of the present study was to assess at a muscular level the modifications brought
      up when running barefoot, using 0mm midsole height running shoe, or using
      classical midsole height running shoes. An EMG-Driven model that combines the
      kinematics, dynamics, and electromyographic data was used to estimate the Triceps
      Surae (TS) muscle forces and fiber behavior during running using different
      footwear conditions. Despite differences at the joint level between barefoot and
      shod running when looking at ankle joint range of motion, or foot-ground angle at
      touchdown, the results showed no effect of footwear neither on the maximal muscle
      forces nor on the relative amount of force produced by each muscle within the TS
      muscle group when wearing different footwear. On the contrary, different
      behaviors of muscle fibers were shown with lower amplitudes of fiber lengths for
      the Gastrocnemii biarticular muscles when running barefoot. This particular
      results reveal that wearing a shoe, even with a very thin sole, could deeply
      modify the intricate muscle-tendon mechanics of running. 

PMID- 25575886
TI  - Recent applications of Vitreoscilla hemoglobin technology in bioproduct synthesis
      and bioremediation.
AB  - Since its first use in 1990 to enhance production of alpha-amylase in E. coli,
      engineering of heterologous hosts to express the hemoglobin from the bacterium
      Vitreoscilla (VHb) has become a widely used strategy to enhance production of a
      variety of bioproducts, stimulate bioremediation, and increase growth and
      survival of engineered organisms. The hosts have included a variety of bacteria,
      yeast, fungi, higher plants, and even animals. The beneficial effects of VHb
      expression are presumably the result of one or more of its activities. The
      available evidence indicates that these include oxygen binding and delivery to
      the respiratory chain and oxygenases, protection against reactive oxygen species,
      and control of gene expression. In the past 4 to 5 years, the use of this "VHb
      technology" has continued in a variety of biotechnological applications in a wide
      range of organisms. These include enhancement of production of an ever wider
      array of bioproducts, new applications in bioremediation, a possible role in
      enhancing aerobic waste water treatment, and the potential to enhance growth and
      survival of both plants and animals of economic importance. 

PMID- 25575885
TI  - An updated view on horseradish peroxidases: recombinant production and
      biotechnological applications.
AB  - Horseradish peroxidase has been the subject of scientific research for centuries.
      It has been used exhaustively as reporter enzyme in diagnostics and
      histochemistry and still plays a major role in these applications. Numerous
      studies have been conducted on the role of horseradish peroxidase in the plant
      and its catalytic mechanism. However, little progress has been made in its
      recombinant production. Until now, commercial preparations of horseradish
      peroxidase are still isolated from plant roots. These preparations are commonly
      mixtures of various isoenzymes of which only a small fraction has been described
      so far. The composition of isoenzymes in these mixed isolates is subjected to
      uncontrollable environmental conditions. Nowadays, horseradish peroxidase regains
      interest due to its broad applicability in the fields of medicine, life sciences,
      and biotechnology in cancer therapy, biosensor systems, bioremediation, and
      biocatalysis. These medically and commercially relevant applications, the recent
      discovery of new natural isoenzymes with different biochemical properties, as
      well as the challenges in recombinant production render this enzyme particularly
      interesting for future biotechnological solutions. Therefore, we reviewed
      previous studies as well as current developments with biotechnological emphasis
      on new applications and the major remaining biotechnological challenge-the
      efficient recombinant production of horseradish peroxidase enzymes. 

PMID- 25575887
TI  - Isolation and characterization of novel lipases/esterases from a bovine rumen
      metagenome.
AB  - Improving the health beneficial fatty acid content of meat and milk is a major
      challenge requiring an increased understanding of rumen lipid metabolism. In this
      study, we isolated and characterized rumen bacterial lipases/esterases using
      functional metagenomics. Metagenomic libraries were constructed from DNA
      extracted from strained rumen fluid (SRF), solid-attached bacteria (SAB) and
      liquid-associated rumen bacteria (LAB), ligated into a fosmid vector and
      subsequently transformed into an Escherichia coli host. Fosmid libraries
      consisted of 7,744; 8,448; and 7,680 clones with an average insert size of 30 to
      35 kbp for SRF, SAB and LAB, respectively. Transformants were screened on spirit
      blue agar plates containing tributyrin for lipase/esterase activity. Five SAB and
      four LAB clones exhibited lipolytic activity, and no positive clones were found
      in the SRF library. Fosmids from positive clones were pyrosequenced and twelve
      putative lipase/esterase genes and two phospholipase genes retrieved. Although
      the derived proteins clustered into diverse esterase and lipase families, a
      degree of novelty was seen, with homology ranging from 40 to 78% following BlastP
      searches. Isolated lipases/esterases exhibited activity against mostly short- to
      medium-chain substrates across a range of temperatures and pH. The function of
      these novel enzymes recovered in ruminal metabolism needs further investigation,
      alongside their potential industrial uses.

PMID- 25575888
TI  - Microbial diversity observed during hemp retting.
AB  - Historically used in textile and paper industry, hemp fibres have started to find
      new applications in composite materials with important economic and ecological
      advantages. However, their applications are limited since manufacturers have some
      difficulties to standardise fabrication processes. This study is a first step
      before selection and isolation of strains that could later be used to optimise
      microbial retting efficiency and hence fibre quality. We studied six samples
      harvested on different ground types, at different dates and with different
      retting durations on field to obtain an exhaustive representation of the process.
      After DNA extraction, total bacteria and fungi associated with stems during
      retting were specifically quantified using real-time PCR. Then, using sequence
      analysis of randomly cloned 16S and 18S ribosomal RNA (rRNA) genes, a
      phylogenetic characterisation of the dominant microorganisms was carried out.
      Quantitatively, we showed that there were 8.1-9.5 log10 16S rRNA gene copies per
      gram of hemp straw for bacteria and 8.6-9.6 log10 18S rRNA gene copies per gram
      for fungi. Qualitatively, we noticed a higher bacterial diversity in comparison
      to fungi. This work showed that in the different samples, the same species were
      present but in significantly different proportions according to ground type,
      harvest dates and retting durations on field. The most frequent bacterial
      sequences were affiliated to species Escherichia coli, Pantoea agglomerans,
      Pseudomonas rhizosphaerae, Rhodobacter sp., Pseudomonas fulva, Rhizobium
      huautlense and Massilia timonae, whereas fungal sequences were principally
      related to the genera Cladosporium and Cryptococcus.

PMID- 25575889
TI  - The relief of microtherm inhibition for p-fluoronitrobenzene mineralization using
      electrical stimulation at low temperatures.
AB  - Low temperature aggravates biological treatment of refractory p
      fluoronitrobenzene (p-FNB) because of microtherm inhibition of microbial
      activity. Considering the potential characterization of energy supply for
      microbial metabolism and spurring microbial activity by electrical stimulation, a
      bioelectrochemical system (BES) was established to provide sustaining electrical
      stimulation for p-FNB mineralization at a low temperature. Electrical stimulation
      facilitated p-FNB treatment and bioelectrochemical reaction rate constants for
      the removal and defluorination of p-FNB at 10  degrees C were 0.0931 and 0.0054
      h(-1), which were higher than the sums of the rates found using a biological
      system and an electrocatalytic system by 62.8 and 64.8%, respectively. At a low
      temperature, microbial activity in terms of dehydrogenase and ATPase was found to
      be higher with electrical stimulation, being 121.1 and 100.1% more active than
      that in the biological system. Moreover, stronger antioxidant ability was
      observed in the BES, which implied a better cold-resistance and relief of
      microtherm inhibition by electrical stimulation. Bacterial diversity analysis
      revealed a significant evolution of microbial community by electrical
      stimulation, and Clostridia was uniquely enriched. One bacterial sequence close
      to Pseudomonas became uniquely predominant, which appeared to be crucial for
      excellent p-FNB treatment performance in the BES at a low temperature. Economic
      evaluation revealed that the energy required to mineralize an extra mole of p-FNB
      was found to be 247 times higher by heating the system than by application of
      electrical stimulation. These results indicated that application of electrical
      stimulation is extremely promising for treating refractory waste at low
      temperatures.

PMID- 25575890
TI  - Regulation of myo-inositol catabolism by a GntR-type repressor SCO6974 in
      Streptomyces coelicolor.
AB  - Myo-inositol is important for Streptomyces growth and morphological
      differentiation. Genomic sequence analysis revealed a myo-inositol catabolic gene
      cluster in Streptomyces coelicolor. Disruption of the corresponding genes in this
      cluster abolished the bacterial growth on myo-inositol as a single carbon source.
      The transcriptions of these genes were remarkably enhanced by addition of myo
      inositol in minimal medium. A putative regulatory gene SCO6974, encoding a GntR
      family protein, is situated in the cluster. Disruption of SCO6974 significantly
      enhanced the transcription of myo-inositol catabolic genes. SCO6974 was shown to
      interact with the promoter regions of myo-inositol catabolic genes using
      electrophoretic mobility shift assays. DNase I footprinting assays demonstrated
      that SCO6974 recognized a conserved palindromic sequence
      (A/T)TGT(A/C)N(G/T)(G/T)ACA(A/T). Base substitution of the conserved sequence
      completely abolished the binding of SCO6974 to the targets demonstrating that
      SCO6974 directly represses the transcriptions of myo-inositol catabolic genes.
      Furthermore, the disruption of SCO6974 was correlated with a reduced sporulation
      of S. coelicolor in mannitol soya flour medium and with the overproduction of
      actinorhodin and calcium-dependent antibiotic. The addition of myo-inositol
      suppressed the sporulation deficiency of the mutant, indicating that the effect
      could be related to a shortage in myo-inositol due to its enhanced catabolism in
      this strain. This enhanced myo-inositol catabolism likely yields dihydroxyacetone
      phosphate and acetyl-CoA that are indirect or direct precursors of the
      overproduced antibiotics. 

PMID- 25575891
TI  - Brain natriuretic peptide as a predictor of weaning from mechanical ventilation
      in patients with respiratory illness.
AB  - BACKGROUND: Cardiovascular dysfunction has been reported as an important
      mechanism of weaning failure. Brain natriuretic peptide (BNP) is a sensitive and
      specific marker for cardiovascular dysfunction. OBJECTIVE: To determine the value
      of BNP levels measured at initiation and end of a 2h spontaneous breathing trial
      (SBT) as a predictor of successful weaning of mechanical ventilation in patients
      with respiratory illness. PATIENTS AND METHODS: Thirty consecutive patients ready
      for weaning were prospectively enrolled in this cross-sectional analytic study
      over a 6-month period. All patients had been on spontaneous mode of weaning for
      at least 2h. Tidal volume, respiratory rate, rapid shallow breathing index
      (RSBI), minute ventilation and PaO2/FiO2 were observed at initiation of SBT. BNP
      was measured at the initiation (BNP1) and at the end of SBT (BNP2). Weaning
      failure is defined as either the failure of SBT or the need for reintubation
      within 48 h following extubation. RESULTS: Out of the 30 included patients, 14
      (46.6%) patients had failed weaning. PaCO2 and BNP2 were significantly higher in
      the patients with failed weaning as compared to those with successful weaning (P
      = 0.025, P = 0.031 respectively). However, BNP1 levels were not statistically
      significant between the 2 groups (P = 0.722). On multiple regression analysis,
      BNP% (percent change in the BNP level during the 2-h SBT) was the only predictor
      of weaning success. As compared to other weaning parameters, BNP% <= 14.9 had the
      best sensitivity, specificity, positive and negative predictive value.
      CONCLUSION: Measuring the percentage change in the BNP level during a SBT may be
      a good predictor of weaning success from mechanical ventilation in respiratory
      patients.

PMID- 25575893
TI  - Preoperative endoscopic ultrasound-guided fine needle aspiration does not impair
      survival of patients with resected pancreatic cancer.
AB  - OBJECTIVE: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) allows
      preoperative tissue confirmation of malignancy, but fear of tumour cell
      dissemination along the needle track has limited its use. We hypothesised that if
      tumour cell dissemination occurs with EUS-FNA, survival after complete resection
      would be impaired. We aimed to evaluate the association of preoperative EUS-FNA
      with long-term outcomes of patients with resected pancreatic cancer. DESIGN:
      Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare
      data, we identified patients with locoregional pancreatic cancer who underwent
      curative intent surgery from 1998 to 2009. The patients who received EUS-FNA
      within the peridiagnostic period were included in the EUS-FNA group. Patients who
      did not receive EUS evaluation or who underwent EUS without FNA were included in
      the non-EUS-FNA group. Overall survival and pancreatic cancer-specific survival
      were compared after controlling for relevant covariates. RESULTS: A total of 2034
      patients with pancreatic cancer were included (90% pancreatic adenocarcinoma). Of
      these, 498 (24%) patients were in EUS-FNA group. Patients with multiple
      comorbidities and more recent diagnosis were more likely to receive EUS-FNA. In
      multivariate analysis, after controlling for age, race, gender, tumour histology,
      tumour stage, tumour grade, tumour location, SEER site, year of diagnosis,
      undergoing percutaneous aspiration/biopsy, Charlson Comorbidity Index, radiation
      and chemotherapy, EUS-FNA was marginally associated with improved overall
      survival (HR 0.84, 95% CI 0.72 to 0.99), but did not affect cancer-specific
      survival (HR 0.87, 95% CI 0.74 to 1.03). CONCLUSIONS: Preoperative EUS-FNA was
      not associated with increased risk of mortality. These data suggest that EUS-FNA
      can be safely performed for the work-up of suspicious pancreatic lesions.

PMID- 25575894
TI  - Expression of Cyclooxygenase-2 in Squamous Cell Carcinoma and Keratoacanthoma and
      its Clinical Significance.
AB  - Cyclooxygenase (COX), also known as prostaglandin endoperoxide synthase,
      catalyzes the conversion of arachidonic acid to prostanoids. There are two
      different isoforms of COX, referred to as COX-1 and COX-2. Overexpression of COX
      2 has been demonstrated in various neoplasms. In this study, we plan to utilize
      COX-2 in understanding the difference of squamous cell carcinoma and
      keratoacanthoma which have many similarities in both morphological and
      histological features. The objective of this study is to study the expression of
      COX-2 in squamous cell carcinoma and keratoacanthoma and to discuss its clinical
      significance. The expression of COX-2 in 55 cases of skin tumors (including 30
      specimens of squamous cell carcinoma, 25 specimens of keratoacanthoma) and 20
      normal skin tissues was detected by immunohistochemical technique. The positive
      expression of COX-2 was found in 73.3 % (22/30) of squamous cell carcinoma and 12
      % (3/25) of keratoacanthoma cases. The positive expression rate of COX-2 in 55
      skin tumors (45.5 %) was significantly higher than that in normal skin tissues (5
      %) (chi (2) = 10.598 %, P < 0.05). The expression of COX-2 in squamous cell
      carcinoma (73.3 %) was significantly higher than that in keratoacanthoma (12 %)
      (chi (2) = 20.69, P < 0.05). COX-2 overexpression may play a potential role in
      the pathogenesis of skin tumors. The positive expression rate of COX-2 is
      associated with the malignant degree of the tumor, and also it may help
      differentiating squamous cell carcinoma from keratoacanthoma. 

PMID- 25575892
TI  - Tear exchange and contact lenses: a review.
AB  - Tear exchange beneath a contact lens facilitates ongoing fluid replenishment
      between the ocular surface and the lens. This exchange is considerably lower
      during the wear of soft lenses compared with rigid lenses. As a result, the
      accumulation of tear film debris and metabolic by-products between the cornea and
      a soft contact lens increases, potentially leading to complications. Lens design
      innovations have been proposed, but no substantial improvement in soft lens tear
      exchange has been reported. Researchers have determined post-lens tear exchange
      using several methods, notably fluorophotometry. However, due to technological
      limitations, little remains known about tear hydrodynamics around the lens and,
      to-date, true tear exchange with contact lenses has not been shown. Further
      knowledge regarding tear exchange could be vital in aiding better contact lens
      design, with the prospect of alleviating certain adverse ocular responses. This
      article reviews the literature to-date on the significance, implications and
      measurement of tear exchange with contact lenses. 

PMID- 25575895
TI  - Study of Anxiety/Depression in Patients with Coronary Heart Disease After
      Percutaneous Coronary Intervention.
AB  - The objective of this study is to study the involvement of anxiety/depression in
      patients with coronary heart disease after percutaneous coronary intervention.
      Inpatients in the Department of Cardiology of Xuzhou Center Hospital from
      December 2012 to July 2014 were divided into stent group (100 cases) and the non
      stent group (50 cases). Fifty cases in the stent group were treated with
      psychological methods, called intervention group, and other 50 cases were
      untreated and called non-intervention group. All patients were assessed for
      anxiety and depression using self-rating anxiety scale and self-rating depression
      scale, 1 day after admission, 1 day after coronary angiography, and when they
      were discharged. No significant differences were observed on biochemical
      criterion, and anxiety scores or depression scores between the stent and the non
      stent groups before percutaneous coronary intervention (P value >0.05 for all).
      After percutaneous coronary intervention, anxiety/depression scores in the
      intervention group and non-intervention group were significantly higher than
      those in the non-stent group (P < 0.05). There were no significant differences
      between the intervention group and the non-intervention group on
      anxiety/depression scores (P > 0.05). On the day of discharge, the
      anxiety/depression scores were the lowest in the intervention group (P < 0.05).
      Coronary artery intervention can increase patients' anxiety/depression, but
      appropriate psychological intervention can reduce the negative emotions. 

PMID- 25575896
TI  - A Randomized Study to Compare the Analgesic Efficacy of Ultrasound-Guided Block
      of Fascia Iliaca Compartment or Femoral Nerve After Patella Fracture Surgery.
AB  - The aim of this study was to compare the analgesic efficacy of the ultrasound
      guided block of femoral nerve or fascia iliaca compartment in patients who
      underwent patella fracture surgery. Fifty patients were blinded and randomized
      into groups treated with continuous fascia iliaca compartment block (CFICB) (n =
      25) or continuous femoral nerve block (CFNB) (n = 25) after patella fracture
      surgery. Analgesic effects of the two methods were assessed and compared.
      Patients from the two groups showed no significant difference in visible analog
      scales at rest and during movement, fentanyl consumption, nausea, and vomiting.
      The time of catheter insertion was significantly shorter in carrying out CFICB
      compared to that in performing CFNB (8.3 +/- 1.4 vs 14.5 +/- 3.0 min). Three of
      the 25 patients in CFNB group experienced dysesthesia of anterior of the thigh, a
      complication which was not observed in CFICB-treated patients. CFICB and CFNB
      were equally effective in relieving pain after the patella fracture surgery.
      However, compared to CFNB, CFICB was found to be safer and easier to perform. 

PMID- 25575897
TI  - Aberrant Methylation Changes Detected in Cutaneous Squamous Cell Carcinoma of
      Immunocompetent Individuals.
AB  - In order to elucidate the role of epigenetic alterations in the development of
      cutaneous squamous cell carcinoma (SCC), we analyzed both gene-specific promoter
      hypermethylation and repetitive sequence hypomethylation in cutaneous SCC as well
      as normal skin tissue samples. We showed that methylation of DAPK1 and CDH13 was
      associated with cutaneous SCC. While methylation frequency of DAPK1 was increased
      from sun-protected normal skin, sun-exposed normal skin, perilesional to lesional
      tissues, methylation of CDH13 was almost exclusively detected in cutaneous SCC
      tissues. Further, methylation of DAPK1 and CDH13 was neither correlated with the
      presence of HPV nor with the presence of p53 mutations in lesional skin tissues.
      Finally, we detected trend of reduced methylation level of repetitive sequences
      from sun-protected, sun-exposed normal skin samples to perilesional, and lesional
      tissues from SCC patients. We conclude that both gene-specific hypermethylation
      and repetitive sequence hypomethylation are present in cutaneous SCC tissue
      samples; these epigenetic changes might represent an independent pathway in the
      development of cutaneous SCC. 

PMID- 25575898
TI  - The Hundred Person Wellness Project and Google's Baseline Study: medical
      revolution or unnecessary and potentially harmful over-testing?
AB  - The Hundred Person Wellness Project is an ambitious pilot undertaking, which aims
      to intensely monitor 100 individuals over 10 months. Patients with abnormal
      findings will be treated, in hopes that this early intervention will avoid, or
      delay, symptomatic disease. Google's "Baseline Study" is of similar scope and
      will enroll 10,000 people over 2 to 3 years. I here speculate that these
      approaches will likely not be effective in preventing disease, but instead, lead
      to unnecessary and potentially harmful interventions. Examples from the cancer
      screening experience over the last 30 years are provided, which show that
      intensive testing may uncover indolent disease or incidental findings which, when
      treated, may cause more harm than good. Additional examples show that aggressive
      treatments for cancer and other diseases do not always lead to better patient
      outcomes. I conclude that the recent advances in omics provide us with
      unprecedented opportunities for high content clinical testing, but such testing
      should be used with caution to avoid the harmful consequences of over-diagnosis
      and over-treatment. Despite the detailed rebuttals by Hood and colleagues in
      another commentary in BMC Medicine, time will show the actual benefits and harms
      of these ambitious initiatives.

PMID- 25575899
TI  - Audiologic impairment associated with bilirubin-induced neurologic damage.
AB  - Hyperbilirubinemia occurs commonly in neonates and is usually mild and transient,
      with no long-lasting sequelae. However, bilirubin-induced neurologic damage may
      occur in some infants. The auditory pathway is the most sensitive part of the
      central nervous system to bilirubin-induced toxicity, and permanent sequelae may
      result from only moderately elevated total serum/plasma bilirubin levels. The
      damage to the auditory system occurs primarily within the brainstem and cranial
      nerve VIII, and manifests clinically as auditory neuropathy spectrum disorder. 

PMID- 25575900
TI  - Neural circuits underlying tongue movements for the prey-catching behavior in
      frog: distribution of primary afferent terminals on motoneurons supplying the
      tongue.
AB  - The hypoglossal motor nucleus is one of the efferent components of the neural
      network underlying the tongue prehension behavior of Ranid frogs. Although the
      appropriate pattern of the motor activity is determined by motor pattern
      generators, sensory inputs can modify the ongoing motor execution. Combination of
      fluorescent tracers were applied to investigate whether there are direct contacts
      between the afferent fibers of the trigeminal, facial, vestibular,
      glossopharyngeal-vagal, hypoglossal, second cervical spinal nerves and the
      hypoglossal motoneurons. Using confocal laser scanning microscope, we detected
      different number of close contacts from various sensory fibers, which were
      distributed unequally between the motoneurons innervating the protractor,
      retractor and inner muscles of the tongue. Based on the highest number of
      contacts and their closest location to the perikaryon, the glossopharyngeal-vagal
      nerves can exert the strongest effect on hypoglossal motoneurons and in agreement
      with earlier physiological results, they influence the protraction of the tongue.
      The second largest number of close appositions was provided by the hypoglossal
      and second cervical spinal afferents and they were located mostly on the proximal
      and middle parts of the dendrites of retractor motoneurons. Due to their small
      number and distal location, the trigeminal and vestibular terminals seem to have
      minor effects on direct activation of the hypoglossal motoneurons. We concluded
      that direct contacts between primary afferent terminals and hypoglossal
      motoneurons provide one of the possible morphological substrates of very quick
      feedback and feedforward modulation of the motor program during various stages of
      prey-catching behavior. 

PMID- 25575901
TI  - Investigation of methanogenic community structures in rural biogas digesters from
      different climatic regions in Yunnan, southwest China.
AB  - Understanding of the microbial community structures of the biogas digesters in
      different climatic regions can help improve the methane production in the
      fermentation process. The methanogenic archaeal diversity in four rural biogas
      digesters (BNA, JSA, LJA, and XGA) was investigated by a culture-independent rRNA
      approach in different climatic regions in Yunnan. Community structure composed of
      711 clones in the all libraries. A total of 33 operational taxonomic units (OTUs)
      were detected, and major groups of methanogens were the orders Methanosarcinales
      and Methanomicrobiales. 63.2 % of all archaeal OTUs belong to the order
      Methanosarcinales which mostly contain acetotrophic methanogens.
      Methanomicrobiales (19.5 % in all OTUs) were detected in considerable number.
      Additionally, there were minor rates of uncultured archaea. The principal
      component analysis indicated that the genus Methanosaeta was mainly affected by
      the fermentation temperatures.

PMID- 25575903
TI  - Erratum to: Comparative assessment of physical and cognitive ergonomics
      associated with robotic and traditional laparoscopic surgeries.

PMID- 25575902
TI  - Independent evolution of four heme peroxidase superfamilies.
AB  - Four heme peroxidase superfamilies (peroxidase-catalase, peroxidase
      cyclooxygenase, peroxidase-chlorite dismutase and peroxidase-peroxygenase
      superfamily) arose independently during evolution, which differ in overall fold,
      active site architecture and enzymatic activities. The redox cofactor is heme b
      or posttranslationally modified heme that is ligated by either histidine or
      cysteine. Heme peroxidases are found in all kingdoms of life and typically
      catalyze the one- and two-electron oxidation of a myriad of organic and inorganic
      substrates. In addition to this peroxidatic activity distinct (sub)families show
      pronounced catalase, cyclooxygenase, chlorite dismutase or peroxygenase
      activities. Here we describe the phylogeny of these four superfamilies and
      present the most important sequence signatures and active site architectures. The
      classification of families is described as well as important turning points in
      evolution. We show that at least three heme peroxidase superfamilies have ancient
      prokaryotic roots with several alternative ways of divergent evolution. In later
      evolutionary steps, they almost always produced highly evolved and specialized
      clades of peroxidases in eukaryotic kingdoms with a significant portion of such
      genes involved in coding various fusion proteins with novel physiological
      functions. 

PMID- 25575904
TI  - Erratum to: Reoperation rates after laparoscopic fundoplication.

PMID- 25575905
TI  - Erratum to: Liquid-injection for preperitoneal dissection of transabdominal
      preperitoneal (TAPP) inguinal hernia repair.

PMID- 25575906
TI  - Erratum to: Standardized laparoscopic NOSE-colectomy is feasible with low
      morbidity.

PMID- 25575907
TI  - Erratum to: A cost evaluation methodology for surgical technologies.

PMID- 25575909
TI  - Growth Patterns of HIV Infected Indian Children in Response to ART: A Clinic
      Based Cohort Study.
AB  - OBJECTIVE: To describe catch-up growth after antiretroviral therapy (ART)
      initiation among children living with human immunodeficiency virus (CLHIV),
      attending a private clinic in India. METHODS: This is a retrospective analysis of
      data of CLHIV attending Prayas clinic, Pune, India. Height and weight z scores
      (HAZ, WAZ) were calculated using WHO growth charts. Catch-up growth post-ART was
      assessed using a mixed method model in cases where baseline and at least one
      subsequent follow-up HAZ/WAZ were available. STATA 12 was used for statistical
      analysis. RESULTS: During 1998 to 2011, 466 children were enrolled (201 girls and
      265 boys; median age = 7 y). A total of 302 children were ever started on ART; of
      which 73 and 76 children were included for analysis for catch up growth in WAZ
      and HAZ respectively. Median WAZ and HAZ increased from -2.14 to -1.34 (p =
      0.007) and -2.42 to -1.94 (p = 0.34), respectively, 3 y post ART. Multivariable
      analysis using mixed model (adjusted for gender, guardianship, baseline age,
      baseline WAZ/HAZ, baseline and time varying WHO clinical stage) showed gains in
      WAZ (coef = 0.2, 95 % CI: -0.06 to 0.46) and HAZ (coef = 0.49, 95 % CI: 0.21 to
      0.77) with time on ART. Lower baseline WAZ/HAZ and older age were associated with
      impaired catch-up growth. Children staying in institutions and with baseline
      advanced clinical stage showed higher gain in WAZ. CONCLUSIONS: The prevalence of
      stunting and underweight was high at ART initiation. Sustained catch-up growth
      was seen with ART. The study highlights the benefit of early ART in achieving
      normal growth in CLHIV.

PMID- 25575908
TI  - Do statins impair cognition? A systematic review and meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: In 2012, the United States Food and Drug Administration (FDA) issued
      a warning regarding potential adverse effects of HMG-CoA reductase inhibitors
      (statins) on cognition, based on the Adverse Events Reporting System and a review
      of the medical literature. We aimed to synthesize randomized clinical trial
      (RCTs) evidence on the association between statin therapy and cognitive outcomes.
      METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL through December 2012,
      and reviewed published systematic reviews of statin treatment. We sought RCTs
      that compared statin treatment versus placebo or standard care, and reported at
      least one cognitive outcome (frequency of adverse cognitive events or
      measurements using standard neuropsychological cognitive test scores). Studies
      reporting sufficient information to calculate effect sizes were included in meta
      analyses. Standardized and unstandardized mean differences were calculated for
      continuous outcomes for global cognition and for pre-specified cognitive domains.
      The main outcome was change in cognition measured by neuropsychological tests; an
      outcome of secondary interest was the frequency of adverse cognitive events
      observed during follow-up. RESULTS: We identified 25 RCTs (all placebo
      controlled) reporting cognitive outcomes in 46,836 subjects, of which 23 RCTs
      reported cognitive test results in 29,012 participants. Adverse cognitive
      outcomes attributable to statins were rarely reported in trials involving
      cognitively normal or impaired subjects. Furthermore, meta-analysis of cognitive
      test data (14 studies; 27,643 participants) failed to show significant adverse
      effects of statins on all tests of cognition in either cognitively normal
      subjects (standardized mean difference 0.01, 95% confidence interval, CI, -0.01
      to 0.03, p = 0.42) or Alzheimer's disease subjects (standardized mean difference 
      0.05, 95% CI -0.19 to 0.10, p = 0.38). CONCLUSIONS: Statin therapy was not
      associated with cognitive impairment in RCTs. These results raise questions
      regarding the continued merit of the FDA warning about potential adverse effects
      of statins on cognition.

PMID- 25575910
TI  - Testicular Tumors in Undescended Testes in Children Below 5 y of Age.
AB  - OBJECTIVE: To evaluate the presentation, treatment and outcome of testicular
      tumors in undescended testes (UDT) in boys below 5 y of age. METHODS: Case
      records of boys below 5 y of age, diagnosed to have germ cell tumors (GCT) in the
      UDT were reviewed. RESULTS: Seven children in the age range of 05-54 mo (mean 26
      mo) were included. While five of these 7 (71 %) presented with abdominal mass
      [one antenatally detected], 2 (29 %) were detected to have a GCT during
      orchiopexy. In three of these five with abdominal mass, the alpha-fetoprotein
      (alphaFP) was markedly elevated. Two of these three with elevated alphaFP were
      endodermal sinus tumors while the third was embryonal carcinoma. The 4th patient
      with an abdominal mass was diagnosed to have an immature teratoma (IMT) while the
      patient with antenatally diagnosed mass had a mature cystic teratoma (MT). Both
      the patients with incidentally detected mass during the orchiopexy had mature
      teratoma (MT). All the seven children are alive and disease free at last follow
      up. CONCLUSIONS: Though rare, boys with impalpable undescended testes may develop
      germ cell tumors early in childhood. These can be managed with chemotherapy and
      resection and have a good disease free outcome.

PMID- 25575911
TI  - Does treatment assignment influence the prognosis of patients with symptomatic
      severe aortic stenosis?
AB  - OBJECTIVE: Aortic valve replacement (AVR) is the standard therapy in patients
      with symptomatic aortic stenosis (AS). In high surgical risk patients,
      alternative therapeutic options to medical treatment (MT) such as trans-catheter
      aortic valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) have been
      proposed. In this study we evaluated whether treatment assignment influences per
      se the prognosis of these subjects. PATIENTS AND METHODS: Criteria for treatment
      assignment were based on patient's clinical conditions, Logistic EuroSCORE and
      other co-morbidities ignored by EuroSCORE. Due to baseline clinical differences
      between patients with diverse treatment assignment, we used propensity score
      matching to achieve balance. RESULTS: 368 patients were studied: 141 underwent
      AVR, 127 TAVI, 49 BAV and 51 MT. 84 events (deaths for all causes) occurred
      during 14 months of follow-up: 11 AVR (8%), 26 TAVI (20%), 18 MT (35%), 29 BAV
      group (59%). Traditional Cox analysis identified treatment assignment as
      independent predictor of events (HR 1.82 [CI 1.10-3.25]) together with lower left
      ventricular ejection fraction, impaired renal function and history of heart
      failure. Matched Cox analysis by propensity score confirmed treatment assignment
      as an independent prognosticator of events (HR 1.90 [CI 1.27-2.85]), and showed
      similar rate events in TAVI and AVR patients, while it was significantly
      increased in BAV and MT patients. CONCLUSIONS: Treatment assignment may influence
      outcome of symptomatic patients with AS.

PMID- 25575912
TI  - Examining the Latent Structure of Acute Stress Disorder Symptoms in Filipino
      Victims of a Flashflood Disaster.
AB  - Although Acute Stress Disorder (ASD) was introduced in the Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition for a number of years
      already, only few studies have examined ASD in its latent level. Utilizing 998
      respondents who experienced a deadly flashflood, the results revealed that of the
      7 models, Dysphoric arousal model fitted best whereas the new DSM-5 single factor
      model received the lowest fit. The findings of the study are pertinent in the
      current changes of ASD in DSM-5 and would elucidate further ASD's latent
      structure that best represent Asian sample, particularly Filipinos. 

PMID- 25575913
TI  - National Healthcare Safety Network report, data summary for 2013, Device
      associated Module.

PMID- 25575914
TI  - Response surface-optimized removal of Reactive Red 120 dye from its aqueous
      solutions using polyethyleneimine enhanced ultrafiltration.
AB  - Retention of toxic dyes with molecular weights lower than the molecular weight
      cut-off (MWCO) of the ultrafiltration membranes can be improved through selective
      binding of the target dyes to a water-soluble polymer, followed by
      ultrafiltration of the macromolecular complexes formed. This method, often
      referred to as polymer enhanced ultrafiltration (PEUF), was investigated in the
      present study, using polyethyleneimine (PEI) as the chelating agent. Model azo
      dye Reactive Red 120 was selected as the poorly biodegradable, target
      contaminant, because of its frequent recalcitrant presence in colored effluents,
      and its eventual ecotoxicological impacts on the environment. The effects of the
      governing process factors, namely, cross flow rate, transmembrane pressure
      polymer to dye ratio and pH, on target dye rejection efficiency were meticulously
      examined. Additionally, each parameter level was statistically optimized using
      central composite design (CCD) from the response surface methodology (RSM)
      toolkit, with an objective to maximize performance efficiency. The results
      revealed high dye retention efficiency over 99%, accompanied with reasonable
      permeate flux over 100L/m(2)h under optimal process conditions. The estimated
      results were elucidated graphically through response surface (RS) plots and
      validated experimentally. The analyses clearly established PEUF as a novel,
      reasonably efficient and economical route for recalcitrant dye treatment. 

PMID- 25575931
TI  - Introductory paragraph.

PMID- 25575930
TI  - Fibulin-1 suppresses endothelial to mesenchymal transition in the proximal
      outflow tract.
AB  - Endothelial to mesenchymal transition (EMT) that occurs during cardiac outflow
      tract (OFT) development is critical for formation of the semilunar valves.
      Fibulin-1 (Fbln1) is an extracellular matrix protein that is present at several
      sites of EMT, including the OFT (i.e., E9.5-10.5). The aim of this study was to
      determine the role of Fbln1 in EMT during the earliest events of OFT development.
      Examination of proximal OFT cushions in Fbln1 null embryos detected
      hypercellularity at both E9.5 (93% increase; p = 0.002) and E10.5 (43% increase;
      p = 0.01) as compared to wild type, suggesting that Fbln1 normally suppresses OFT
      endocardial cushion EMT. This was supported by studies of proximal OFT cushion
      explants, which showed that explants from Fbln1 null embryos displayed a 58%
      increase in cells migrating from the explants as compared to wild type (p =
      0.005). We next evaluated the effects of Fbln1 deficiency on the expression of
      factors that regulate proximal OFT EMT. At E9.5, Fbln1 null proximal OFT
      endocardium and EMT-derived mesenchyme showed increased TGFbeta2 (58% increase; p
      = 0.01) and increased Snail1-positive nuclei (27% increase; p = 0.0003).
      Histological examination of OFT cushions in Fbln1 null embryos (E9.5) also
      detected cells present in the cushion that were determined to be erythrocytes
      based on round morphology, autofluorescence, and positive staining for
      hemoglobin. Erythrocytes were also detected in Fbln1 null OFT cushions at E10.5.
      Together, the findings indicate that Fbln1 normally suppresses proximal OFT EMT
      preventing proximal cushion hypercellularity and blood cell accumulation. 

PMID- 25575932
TI  - Effects of training on upper limb function after cervical spinal cord injury: a
      systematic review.
AB  - OBJECTIVE: To summarize the evidence for the effectiveness of exercise training
      in promoting recovery of upper extremity function after cervical spinal cord
      injury. DATA SOURCES: Medline, Cochrane, CINAHL, EMBASE and PEDro were used to
      search the literature. REVIEW METHODS: Two reviewers independently selected and
      summarized the included studies. Methodological quality of the selected articles
      was scored using the Downs and Black checklist. RESULTS: A total of 16 studies
      were included, representing a total of 426 participants. Overall, the internal
      validity and reporting of the studies was fair to good, while power and external
      validity were poor. Interventions included exercise therapy, electrical
      stimulation, functional electrical stimulation, robotic training and repetitive
      transcranial magnetic stimulation. Most of the studies reported improvements in
      muscle strength, arm and hand function, activity of daily living or quality of
      life after intervention. CONCLUSIONS: Training including exercise therapy,
      electrical stimulation, functional electrical stimulation of the upper limb
      following cervical spinal cord injury leads to improvements in muscle strength,
      upper limb function and activity of daily living or quality of life. Further
      research is needed into the effects of repetitive transcranial magnetic
      stimulation and robotic training on upper limb function.

PMID- 25575934
TI  - Beyond memory: a focus on the other neuropsychiatric symptoms of dementia.

PMID- 25575935
TI  - An unsubstantiated conclusion.

PMID- 25575936
TI  - Emerging drugs for the treatment of axial and peripheral spondyloarthritis.
AB  - INTRODUCTION: The topic under discussion is of strong relevance to the field of
      spondyloarthritis (SpA) because, in addition to established biological, there are
      new promising compounds. The reason for the review is to put all available data
      together to allow for an overview on recent developments and to especially inform
      readers about emerging drugs, biologics and small molecules in the field of SpA.
      AREAS COVERED: This review on new therapies in axial and peripheral SpA
      comprising psoriatic arthritis (PsA) shows, that, in addition to the established
      anti-TNF agents infliximab, etanercept, adalimumab, golimumab, certolizumab and
      the first biosimilar approved in the EU, there are at least two emerging
      biologics in the field of SpA: ustekinumab, a compound targeting IL12/IL-23 via
      the p40 subunit of both cytokines works for psoriasis and PsA and probably also
      for Crohn's disease, and the anti-IL-17 antibody secukinumab which has also been
      shown to work in psoriasis, both compounds seem to also work in ankylosing
      spondylitis. In addition, the potential of two small molecules, apremilast a
      phoshodiesterase4 inhibitor and tofacitinib, a januskinase inhibitor is
      discussed. EXPERT OPINION: Since, in contrast to rheumatoid arthritis, the
      therapeutic array in SpA is currently limited to TNF-blockers, and since there is
      still an unmet need because some patients do not respond to anti-TNF therapy at
      all or they loose response, new agents with a different mechanism of action are
      eagerly awaited.

PMID- 25575937
TI  - Impact of bevacizumab administered dose on overall survival of patients with
      progressive glioblastoma.
AB  - Bevacizumab (BEV, Avastin((r))) produces durable objective radiological responses
      of 20-26 %, median response durations of 16-18 weeks, and median overall survival
      (mOS) of 31-40 weeks. While the use of BEV is well-established, the lack of dose
      response studies in glioblastoma (GBM) patients raises the question whether
      current dosing practice is optimal. As a result of differing approaches to BEV
      dosing that ranged from the FDA approved package insert dose of 10 mg/kg every 2
      weeks to 7.5 mg/kg every 3-4 weeks, among physicians within Northern California
      Kaiser Permanente hospitals over 4+ years, we did an IRB-approved retrospective
      analysis of patients seen in Northern California Kaiser Permanente facilities and
      treated with BEV. Between September 1, 2008 and August 31, 2013, 181 patients
      received BEV for tumor progression/recurrence starting 2.6 weeks after completion
      of chemoradiation. The integrated BEV administered dose-week (AUCBEV) for all
      patients had a median AUCBEV of 3.6 mg.wk/kg). Maximum likelihood analysis found
      patients over 65 years did worse than younger patients (p = 0.004), women lived
      longer (p = 0.002), and patients treated below the AUCBEV did better than those
      treated above the median AUCBEV (p = 0.003). mOS for BEV starting 1 month after
      chemoradiation was 45 versus 68 weeks (p = 0.012) and BEV starting 3 months after
      chemoradiation was 40 versus 74 weeks (p = 0.0085). Dosing BEV at half the
      standard dose for progressive/recurrent GBM was at least equivalent to or, maybe
      better than standard dosing. Unexplained was the observation that females had
      longer OS with BEV than males.

PMID- 25575939
TI  - Enlarging scalp mass.

PMID- 25575940
TI  - Efficacy of fluticasone propionate/formoterol fumarate in the treatment of
      asthma: a pooled analysis.
AB  - BACKGROUND: Fluticasone propionate and formoterol fumarate have been combined in
      a single inhaler (fluticasone/formoterol; flutiform((r))) for the maintenance
      treatment of asthma. This pooled analysis assessed the efficacy of
      fluticasone/formoterol versus fluticasone in patients who previously received
      inhaled corticosteroids. METHODS: Data were pooled from five randomised studies
      in patients with asthma (aged >=12 years) treated for 8 or 12 weeks with
      fluticasone/formoterol (100/10, 250/10 or 500/20 MUg b.i.d.; n = 528 delivered
      via pMDI) or fluticasone alone (100, 250 or 500 MUg b.i.d.; n = 527). RESULTS:
      Fluticasone/formoterol provided significantly greater increases than fluticasone
      alone in mean morning forced expiratory volume in 1 second (FEV1) from pre-dose
      at baseline to 2 hours post-dose at study end (least-squares mean [LSM] treatment
      difference: 0.146L; p < 0.001) and in pre-dose FEV1 from baseline to study end
      (LSM treatment difference: 0.048 L; p = 0.043). Compared with fluticasone,
      fluticasone/formoterol provided greater increases in the percentage of asthma
      control days (no symptoms, no rescue medication use and no sleep disturbance due
      to asthma) from baseline to study end (LSM treatment difference: 8.6%; p <
      0.001), and was associated with a lower annualised rate of exacerbations (rate
      ratio: 0.71; p = 0.014). CONCLUSIONS: In summary, fluticasone/formoterol provides
      clinically significant improvements in lung function and asthma control measures,
      with a lower incidence of exacerbations than fluticasone alone.

PMID- 25575938
TI  - Prognosis of glioblastoma with faint MGMT methylation-specific PCR product.
AB  - Methylation-specific polymerase chain reaction (MSP) for the promoter methylation
      status of O(6)-methylguanine-DNA-methyltranferase (MGMT) gene theoretically
      provides a positive or negative result. However, the faint MSP product is
      difficult to interpret. The aim of this study was to evaluate the significance of
      faint MSP product in glioblastoma (GBM). Critical concentrations of methylated
      control DNA, i.e., 100, 1, 0.5 and 0 % were run parallel with 116 newly diagnosed
      GBMs in order to standardize the interpretation and to distinguish positive (+),
      equivocal (+/-), and negative (-; unmethylated) results. Cases with the faint MSP
      product and its intensity between those of 1 and 0.5 % DNA controls were
      considered equivocal (+/-). MGMT methylation quantifications were also determined
      by quantitative real-time MSP (qMSP) and pyrosequencing (PSQ), and protein
      expression was detected by immunohistochemistry. There were significant
      correlations between MSP and all the aforementioned studies. The concordance
      rates between the MSP+ and qMSP+ cases, as well as the MSP- and qMSP- cases were
      100 %, and the MSP+/- cases comprised 76.5 % of qMSP+ cases and 23.5 % of qMSP-
      cases. PSQ study showed that heterogeneous methylation was more frequently
      encountered in the MSP+/- cases. Multivariate analyses disclosed that although
      the overall survival of the MSP+/- cases was indistinct from that of the MSP+
      cases, its progression free survival was significantly worse and was indistinct
      from that of the MSP- cases. In conclusion, GBMs with faint MGMT MSP products
      should be distinguished from MSP+ cases as their behaviors were different.

PMID- 25575941
TI  - Bias in estimators of archaic admixture.
AB  - This article evaluates bias in one class of methods used to estimate archaic
      admixture in modern humans. These methods study the pattern of allele sharing
      among modern and archaic genomes. They are sensitive to "ghost" admixture, which
      occurs when a population receives archaic DNA from sources not acknowledged by
      the statistical model. The effect of ghost admixture depends on two factors:
      branch-length bias and population-size bias. Branch-length bias occurs because a
      given amount of admixture has a larger effect if the two populations have been
      separated for a long time. Population-size bias occurs because differences in
      population size distort branch lengths in the gene genealogy. In the absence of
      ghost admixture, these effects are small. They become important, however, in the
      presence of ghost admixture. Estimators differ in the pattern of response.
      Increasing a given parameter may inflate one estimator but deflate another. For
      this reason, comparisons among estimators are informative. Using such
      comparisons, this article supports previous findings that the archaic population
      was small and that Europeans received little gene flow from archaic populations
      other than Neanderthals. It also identifies an inconsistency in estimates of
      archaic admixture into Melanesia.

PMID- 25575942
TI  - Modeling the genealogy of a cultural trait.
AB  - The mathematical study of genealogies has yielded important insights in
      population biology, such as the ability to estimate the time to the most recent
      common ancestor (MRCA) of a sample of genetic sequences or of a group of
      individuals. Here we introduce a model of cultural genealogies that is a step
      toward answering similar questions for cultural traits. In our model individuals
      can inherit from a variable, potentially large number of ancestors, rather than
      from a fixed, small number of ancestors (one or two) as is typical of genetic
      evolution. We first show that, given a sample of individuals, a cultural common
      ancestor does not necessarily exist. We then introduce a related concept: the
      most recent unique ancestor (MRUA), i.e., the most recent single individual who
      is the earliest cultural ancestor of the sample. We show that, under neutral
      evolution, the time to the MRUA can be staggeringly larger than the time to MRCA
      in a single ancestor model, except when the average number of learning
      opportunities per individuals is small. Our results point out that the properties
      of cultural genealogies may be very different from those of genetic genealogies,
      with potential implications for reconstructing the histories of cultural traits. 

PMID- 25575944
TI  - Tanshinone IIA attenuates the cerebral ischemic injury-induced increase in levels
      of GFAP and of caspases-3 and -8.
AB  - Tanshinone IIA (TSA) is a lipid soluble agent derived from the root of Salvia
      miltiorrhiza (Danshen). This plant is a traditional Chinese herb, which has been
      used widely in China especially for enhancing circulation. However mechanisms
      underlying its efficacy remain poorly understood. The present study was designed
      to illuminate events that may underlie the apparently neuroprotective effects of
      TSA following ischemic insult. Adult Sprague-Dawley rats were subjected to
      transient focal cerebral ischemia by use of a middle cerebral artery occlusion
      model. They were then randomly divided into a sham-operated control group, and
      cerebral ischemia/reperfusion groups receiving a two-hour occlusion. Further
      subsets of groups received the same durations of occlusion or were sham-operated
      but then received daily i.p. injections of high or low doses of TSA, for seven or
      15days. Hematoxylin and eosin staining revealed lesions in the entorhinal cortex
      of both rats subject to ischemia and to a lesser extent to those receiving TSA
      after surgery. Levels of glial fibrillary acidic protein (GFAP), caspase-3 and
      caspase-8, were quantified by both immunohistochemistry and Western blotting. TSA
      treatment after middle cerebral artery occlusion, markedly reduced infarct size,
      and reduced the expression of caspase-3 and caspase-8. These changes were
      considered protective and were generally proportional to the dose of TSA used.
      These results suggest that TSA may effect neuroprotection by way of reduction of
      the extent of cell inflammation and death within affected regions.

PMID- 25575943
TI  - Between the primate and 'reptilian' brain: Rodent models demonstrate the role of
      corticostriatal circuits in decision making.
AB  - Decision making can be defined as the flexible integration and transformation of
      information from the external world into action. Recently, the development of
      novel genetic tools and new behavioral paradigms has made it attractive to study
      behavior of all kinds in rodents. By some perspectives, rodents are not an
      acceptable model for the study of decision making due to their simpler behavior
      often attributed to their less extensive cortical development when compared to
      non-human primates. We argue that decision making can be approached with a common
      framework across species. We review insights from comparative anatomy that
      suggest the expansion of cortical-striatal connectivity is a key development in
      evolutionary increases in behavioral flexibility. We briefly review studies that
      establish a role for corticostriatal circuits in integrative decision making.
      Finally, we provide an overview of a few recent, highly complementary rodent
      decision making studies using genetic tools, revealing with new cellular and
      temporal resolution how, when and where information can be integrated and
      compared in striatal circuits to influence choice. 

PMID- 25575945
TI  - The effects of social defeat on behavior and dopaminergic markers in mice.
AB  - The present study investigated the effects of chronic social defeat stress on
      several behavioral parameters, and the expression of dopaminergic markers, i.e.,
      dopamine D1 receptors (D1Rs), dopamine D2 receptors (D2Rs), and dopamine and
      cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein-32 (DARPP-32), in
      the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HIP) of mouse
      brains. After 10days of social defeat stress, the defeated mice were divided into
      two groups: one group underwent a series of behavioral tests. The other group was
      sacrificed on the 11th day and tissue samples were collected for Western
      blotting. The behavioral tests comprised tests of locomotion, light/dark
      preference, social interaction, as well as the novel object recognition test
      (NORT), Morris water maze, and forced swimming test (FST). We measured the
      expression of D1Rs, D2Rs, total DARPP-32, phospho-Thr34 or Thr75-DARPP-32 using
      Western blotting. The defeated mice showed increased anxiety- and depression-like
      behaviors, and impaired cognition. No significant differences in D1Rs and D2Rs
      expression were shown between defeated and control mice in any area studied. A
      significantly increased expression in total DARPP-32, and phospho-DARPP-32 was
      observed in the PFC or AMY of defeated mice. These data suggest that alterations
      in dopaminergic markers may be involved in anxiety- and depression-like
      behaviors, and cognitive impairment induced by social defeat stress.

PMID- 25575946
TI  - Plastic oscillators and fixed rhythms: changes in the phase of clock-gene rhythms
      in the PVN are not reflected in the phase of the melatonin rhythm of grass rats.
AB  - The same clock-genes, including Period (PER) 1 and 2, that show rhythmic
      expression in the suprachiasmatic nucleus (SCN) are also rhythmically expressed
      in other brain regions that serve as extra-SCN oscillators. Outside the
      hypothalamus, the phase of these extra-SCN oscillators appears to be reversed
      when diurnal and nocturnal mammals are compared. Based on mRNA data, PER1 protein
      is expected to peak in the late night in the paraventricular nucleus of the
      hypothalamus (PVN) of nocturnal laboratory rats, but comparable data are not
      available for a diurnal species. Here we use the diurnal grass rat (Arvicanthis
      niloticus) to describe rhythms of PER1 and 2 proteins in the PVN of animals that
      either show the species-typical day-active (DA) profile, or that adopt a night
      active (NA) profile when given access to running wheels. For DA animals housed
      with or without wheels, significant rhythms of PER1 or PER2 protein expression
      featured peaks in the late morning; NA animals showed patterns similar to those
      expected from nocturnal laboratory rats. Since the PVN is part of the circuit
      that controls pineal rhythms, we also measured circulating levels of melatonin
      during the day and night in DA animals with and without wheels and in NA wheel
      runners. All three groups showed elevated levels of melatonin at night, with
      higher levels during both the day and night being associated with the levels of
      activity displayed by each group. The differential phase of rhythms in the clock
      gene protein in the PVN of diurnal and nocturnal animals presents a possible
      mechanism for explaining species differences in the phase of autonomic rhythms
      controlled, in part, by the PVN. The present study suggests that the phase of the
      oscillator of the PVN does not determine that of the melatonin rhythm in diurnal
      and nocturnal species or in diurnal and nocturnal chronotypes within a species.

PMID- 25575947
TI  - The endocannabinoid system within the dorsal lateral geniculate nucleus of the
      vervet monkey.
AB  - The endocannabinoid system mainly consists of cannabinoid receptors type 1 (CB1R)
      and type 2 (CB2R), their endogenous ligands termed endocannabinoids (eCBs), and
      the enzymes responsible for the synthesis and degradation of eCBs. These
      cannabinoid receptors have been well characterized in rodent and monkey retinae.
      Here, we investigated the expression and localization of the eCB system beyond
      the retina, namely the first thalamic relay, the dorsal lateral geniculate
      nucleus (dLGN), of vervet monkeys using immunohistochemistry methods. Our results
      show that CB1R is expressed throughout the dLGN with more prominent labeling in
      the magnocellular layers. The same pattern is observed for the degradation
      enzyme, fatty acid amide hydrolase (FAAH). However, the synthesizing enzyme N
      acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) is expressed
      homogenously throughout the dLGN with no preference for any of the layers. These
      proteins are weakly expressed in the koniocellular layers. These results suggest
      that the presence of the eCB system throughout the layers of the dLGN may
      represent a novel site of neuromodulatory action in normal vision. The larger
      amount of CB1R in the dLGN magnocellular layers may explain some of the
      behavioral effects of cannabinoids associated with the integrity of the dorsal
      visual pathway that plays a role in visual-spatial localization and motion
      perception.

PMID- 25575948
TI  - Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic
      ovarian syndrome.
AB  - OBJECTIVE: To study the relationship between the lactonase activities and status
      of paraoxonase 1 (PON1) and its association with the PON1 genetic polymorphisms
      in women with polycystic ovarian syndrome (PCOS). DESIGN: A case-control study.
      METHODS: A total of 455 PCOS patients and 441 control women were included in this
      study. The lactonase activities and concentrations of PON1 were assayed using 5
      thiobutyl butyrolactone (TBBL) and 7-O-diethylphosphoryl-3-cyano-4-methyl-7
      hydroxycoumarin (DEPCyMC) respectively. A normalized lactonase activity (NLA) was
      estimated based on the ratio of TBBLase:DEPCyMCase activity. The PON1 genotypes,
      serum malondialdehyde (MDA) levels and total antioxidant capacity were analyzed.
      RESULTS: The lactonase activities and levels of PON1 were higher in PCOS patients
      than in the control women. However, the NLA did not significantly differ between
      groups. The -108C->T variation of the PON1 gene showed decreased lactonase
      activities and levels of PON1 in a genotype-dependent manner (CC>CT>TT); the 192Q
      >R variation of the PON1 gene showed increased PON1 lactonase activities and NLA;
      and the 55L->M variation of the PON1 gene showed decreased lactonase activities
      and levels of PON1 but an increased NLA. A multivariable regression analysis
      showed that the -108C/T, 192Q/R, and 55L/M variations of the PON1 gene, serum
      apolipoprotein A1, and MDA levels were significant predictors of PON1 lactonase
      activity, PON1 level, and NLA. CONCLUSIONS: The serum lactonase activities and
      concentrations of PON1 are increased in PCOS patients. The increased oxidative
      stress and the -108C/T, 192Q/R, and 55L/M genetic polymorphisms of PON1 may be
      associated with these changes.

PMID- 25575950
TI  - The incidence of Staphylococcus aureus ST8-USA300 among French pediatric
      inpatients is rising.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) formerly colonized and
      infected only inpatients in hospitals, but have been reported in community
      settings worldwide over the last 20 years. In France, the prevalence of such MRSA
      remains low and outbreaks have, until now, been mainly due to the ST80 clone.
      However, there were two outbreaks of MRSA clone ST-USA300 recently in France,
      including one involving children. To investigate epidemiological developments, we
      studied the 77 MRSA isolated from pediatric patients hospitalized between 2008
      and 2013 in three French hospitals. The median incidence of MRSA was stable and
      low (0.137 per 100 admissions). The prevalence of Panton-Valentine leukocidin
      (PVL)-positive MRSA was high (33.8 %). The 26 PVL-positive MRSA were genetically
      diverse, with two clones being predominant: ST80 (12 isolates, 46.1 %) and ST8
      USA300 (8 isolates, 30.8 %). The incidence of ST8-USA300 increased over the 6
      year period. We believe that screening for ST8-USA300 should be improved: medical
      biologists should be encouraged to search for PVL genes in all MRSA isolates
      recovered from abscesses, whatever the susceptibility pattern of the isolate, and
      not only when suggestive of ST80. 

PMID- 25575949
TI  - The levels of antibodies to Panton-Valentine leukocidin (PVL) vary with PVL
      prevalence along a north-to-south gradient.
AB  - Recent research on Staphylococcus aureus vaccine development has focused on
      active immunization against Panton-Valentine leukocidin (PVL), a potent
      leukotoxin associated with both superficial and severe deep-seated infections.
      PVL prevalence is highly variable worldwide, but it is unknown to what extent
      immunity to PVL varies between patients from geographic areas with different PVL
      positive S. aureus prevalences. We conducted a retrospective multicentric study
      of anti-PVL and anti-alpha-toxin (Hla) antibody levels in uninfected adult
      patients from France (low PVL prevalence; n = 200), Algeria (moderate prevalence;
      n = 143), and Senegal (high prevalence; n = 228). The antibody levels were
      quantified by an enzyme-linked immunosorbent assay (ELISA) procedure. Because Hla
      is present in virtually all S. aureus strains, its corresponding antibody levels
      were considered to reflect population exposure to S. aureus. Compared with French
      participants, the average anti-PVL antibody levels were 2.5-fold and 8.2-fold
      higher in Algerian and Senegalese participants, respectively (p < 0.001).
      Conversely, anti-Hla antibody levels did not differ between participants from the
      three countries, suggesting that the observed differences in anti-PVL antibody
      levels were not biased by variations in population exposure to S. aureus. Hence,
      anti-PVL antibody levels in the general populations of France, Algeria, and
      Senegal vary widely and match variations in PVL-positive S. aureus strain
      prevalence, with an increasing north-to-south gradient. To conclude, immunity to
      PVL in a given population correlates with local PVL prevalence. This finding can
      help to inform PVL vaccine strategies. 

PMID- 25575951
TI  - Effect of a silane coupling agent on the mechanical properties of a
      microfibrillated cellulose composite.
AB  - Composite materials reinforced with microfibrillated cellulose (MFC) fibers were
      prepared and characterized in terms of their mechanical properties. The surface
      of the MFC fibers was treated with a silane coupling reagent having an NH2
      functional group to improve fiber-matrix adhesion. Due to the unique structure of
      the MFC, which consists of nano-order-scale interconnected fibrils and
      microfibrils with greatly expanded surface area and submicron pore size compared
      to conventional cellulose, it was possible to enhance the effect of silane
      coupling agent and thereby improve the compatibility between the fibers and
      matrix and also the dispersibility of fibers. The Young's modulus was
      significantly increased to more than 70%. 

PMID- 25575952
TI  - Virtual screening of molecular properties of chitosan and derivatives in search
      for druggable molecules.
AB  - Druggability of chitosan monomer and Schiff bases as well as reduced Schiff base
      derivatives of chitosan were examined. Oral bioavailability and bioactivity of
      all these molecules against selected drug targets as well as ADME/Tox studies
      were conducted. All the molecules satisfied Lipinski's rule of five confirming
      their oral bioavailability. They also show good bioactivity score for protease
      and enzyme inhibition. ADME/Tox studies conducted shows that almost all the
      derivatives are free from toxicity risks. It is observed that these molecules
      exhibit fairly good drug score and are orally viable molecules. Chelation of
      chitosan and its derivatives with essential metal ions might be the mechanism
      driving their bioactivity. Thus chitosan monomer and the derivatives studied, can
      serve as good lead molecules for further research. 

PMID- 25575953
TI  - Aggression in Huntington's disease: a systematic review of rates of aggression
      and treatment methods.
AB  - Aggression is commonly reported in individuals with Huntington's disease (HD).
      While correlating factors for aggression are often speculated about, features
      that are associated with, and contribute to, aggression in this population have
      not been clearly determined. This systematic review investigates rates of
      aggression and treatment options for aggression in HD. A number of key findings
      were revealed. Studies reporting on rates of aggression revealed that its
      prevalence is high, falling between 22 and 66 percent in the majority of studies.
      Aggression may be more common in males with HD, and is also found in higher rates
      in individuals who experience frequent falls, have obsessive-compulsive symptoms
      and suicidal ideation. There is little research investigating antecedents for
      aggression in HD. A wide variety of psychotropic medications have been reported
      in the literature to treat individuals with HD and aggressive behaviour. However,
      due to methodological limitations, no treatment recommendations can be made,
      based on the current literature. Two non-medication therapies have been
      investigated, behaviour support and sensory modulation intervention. However,
      again, due to methodological limitations with these studies, further research is
      needed before they can be recommended as frontline interventions. This review
      highlights the need for further methodologically rigorous studies investigating
      the treatment of aggression in HD. 

PMID- 25575954
TI  - Comparison of phosphodiesterase 10A, dopamine receptors D1 and D2 and dopamine
      transporter ligand binding in the striatum of the R6/2 and BACHD mouse models of
      Huntington's disease.
AB  - BACKGROUND: Phosphodiesterase 10A (PDE10A) is expressed at high levels in the
      striatum and has been proposed both as a biomarker for Huntington's disease
      pathology and as a target for intervention. OBJECTIVE: PDE10A radiotracers have
      been successfully used to measure changes in binding density in Huntington's
      disease patients, but little is known about PDE10A binding in mouse models that
      are used extensively to model pathology and test therapeutic interventions.
      METHODS: Our study investigated changes in PDE10A binding using the selective
      tracer 3H-7980 at specific ages of two Huntington's disease transgenic mouse
      models: R6/2, a short-lived model carrying exon-1 of mutant HTT and BACHD, a
      longer-lived model carrying full-length mutant HTT. PDE10A binding was compared
      to binding of known markers of striatal atrophy in Huntington's disease, e.g.
      dopamine transporter (DAT) and dopamine receptors D1 and D2. RESULTS: We found
      that in the R6/2 model at 6 weeks of age, mice showed high variability of
      binding, however binding of all ligands was significantly decreased at 8 and 12
      weeks of age. In contrast, no changes were detectable in the BACHD model at 8, 10
      or 12 month of age. CONCLUSIONS: These findings suggest that radiotracer binding
      of PDE10A, DAT, D1 and D2 receptor in the R6/2 model may be a good indicator of
      striatal pathological changes that are observed in Huntington's disease patients,
      and that the first 12 months in the BACHD model may be more reflective of early
      stages of the disease.

PMID- 25575955
TI  - An automated and quantitative method to evaluate progression of striatal
      pathology in Huntington's disease transgenic mice.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a
      polyglutamine expansion in the Huntingtin protein which results in the selective
      degeneration of striatal medium spiny neurons (MSN). A number of genetic mouse
      models have been developed to model HD phenotype. Most of these models display
      impaired performance in motor coordination assays and variety of
      neuropathological abnormalities. Quantitative neuropathological assessment in
      these mice requires application of stereological techniques and very labor
      intensive and time consuming. Here, we report a development of a novel paradigm
      that simplifies and accelerates quantitative evaluation of striatal atrophy in HD
      mice. To achieve this goal, we crossed YAC128 HD transgenic mice with Rgs9-EGFP
      mice. In Rgs9-EGFP mice the EGFP transgene is expressed selectively in MSN
      neurons at high levels. Using high resolution fluorescence laser scanning imager,
      we have been able to precisely measure striatal area and intensity of EGFP
      expression in coronal slices from these mice at 2 months, 4 months and 9 months
      of age. Using this approach, we demonstrated significant reduction in striatal
      volume in YAC128 mice at 4 months and 9 months of age when compared to wild type
      littermates. We evaluated behavior performance of these mice at 2 months, 4
      months and 6 months of age and demonstrated significant impairment of YAC128 mice
      in beam walk assay at 4 months and 6 months of age. This new mouse model and the
      quantitative neuropathological scoring paradigm may simplify and accelerate
      discovery of novel neuroprotective agents for HD. 

PMID- 25575956
TI  - We can predict when driving is no longer safe for people who have HD using
      standard neuropsychological measures.
AB  - BACKGROUND: Early cognitive dysfunction in Huntington's Disease (HD) is typically
      of a subcortical frontal executive type, with bradyphrenia, poor spatial and
      working memory, poor planning and organization, a lack of judgment, and poor
      mental flexibility. Although there is literature suggesting a correlation between
      deficits in speed of processing, working memory and executive function on driving
      competency, there is little direct evidence comparing these declines on tests to
      actual driving skills. OBJECTIVE: The current study examines the utility of
      specific neuropsychological measures in predicting actual driving competency in
      patients with HD. METHODS: Fifty-two patients at the UConn Health HD Program
      underwent yearly neuropsychological evaluations and were included in this study.
      Four scales were chosen a priori to predict driving impairment because of their
      reported relationship to driving ability. Within each test category, subjects who
      scored below the threshold suggestive of neurological impairment were found to
      have results within the impaired range (1.5 standard deviations below corrective
      normative data). A referral to the Connecticut Department of Motor Vehicles (DMV)
      for a driving evaluation was subsequently made on patients who were found
      impaired on any two of these tests. RESULTS: The authors found a strong
      relationship between scores on a simple battery of four neuropsychological tests
      and driving competency. CONCLUSIONS: This short battery may prove of pragmatic
      value for clinicians working with people with HD and their families.

PMID- 25575957
TI  - Interventional differences among Huntington's disease patients by disease
      progression in commercial and medicaid populations.
AB  - BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disease
      that spans distinct disease stages over 15-20 years. Various interventions are
      available which may allow patients to live outside of a nursing home for a longer
      time. However, little is known about use of these interventions by disease stage
      and by insurance type. OBJECTIVE: We compared use of interventions among early,
      middle and late stages of HD in commercial (C) and Medicaid (M) health insurance
      populations. METHODS: HD patients (ICD-9-CM 333.4) were identified from Thomson
      Reuters' MarketScan C and M database (2002-2009) and hierarchically grouped into
      disease stages based upon the presence of defining clinical markers. RESULTS: A
      total of 1,272 HD patients (752/520 C/M) were identified. While stage
      distribution was nearly uniform in the C database - 34.0/35.5/34.0%
      (early/middle/late stage) - in the M population the majority were late stage
      (74.0%). Overall mean age was similar between C and M populations. Among late
      stage patients, more M patients resided in a nursing home (M:73.8% v. C:40.6%)
      and received hospice care (M:18.4% v. C:11.3%). Physical therapy (PT) and home
      assistance were the most frequent interventions used by middle-stage patients,
      however more C patients received PT (C:64.0% v. M:37.1%) while more M patients
      received home assistance (M:75.3% v. C:53.2%). Among late-stage patients, PT was
      also higher in the C population (56.3% v. 48.3%). More M patients had assistive
      devices at home in both middle (M:25.8% v. C:9.7%) and late stages (M:35.6%
      v.C:23.4%). CONCLUSIONS: Apparent interventional differences emerged which varied
      by disease stage and insurance type.

PMID- 25575958
TI  - Region-specific pro-survival signaling and global neuronal protection by wild
      type Huntingtin.
AB  - BACKGROUND: Huntington's disease (HD), caused by polyglutamine expansion in
      huntingtin (Htt), results in severe neurodegeneration in the striatum, and to a
      lesser extent, cortex and hippocampus. In contrast, non-expanded huntingtin
      (wildtype, wtHtt) enhances pro-survival trophic factor BDNF expression and
      protects striatal neurons from excitotoxicity, a mechanism thought to contribute
      to HD pathophysiology; however, it is unknown whether these effects of wtHtt
      extend to other brain areas. OBJECTIVE: Test wtHtt's role in pro-survival
      signaling and neuroprotection in striatum, cortex and hippocampus. METHODS:
      Levels of nuclear phosphorylated cAMP response element-binding protein (pCREB), a
      regulator of pro-survival gene transcription, and resistance to NMDA-induced
      apoptosis in primary neuronal cultures - hippocampal and corticostriatal co
      culture -were assessed using immunocytochemistry and excitotoxicity assays,
      respectively. Cultures from wild-type FVB/N (WT) mice were compared with those
      from YAC18 mice on an FVB/N background, expressing both human, full-length wtHtt
      and normal levels of murine Htt. RESULTS: Basal pCREB was higher in YAC18
      striatal but not cortical or hippocampal neurons; however, all three types showed
      decreased apoptosis in YAC18 vs. WT cultures. Increased striatal neuronal pCREB
      required wtHtt overexpression in both cortical and striatal neurons. Reduced
      response to exogenous BDNF, or its soluble scavenger TrkB-Fc, suggested enhanced
      BDNF signaling contributes to increased YAC18 striatal pCREB. CONCLUSION: Basal
      pro-survival signaling does not predict neuronal vulnerability to apoptosis in
      our culture system, since wtHtt overexpression elevates basal pCREB selectively
      in striatal neurons but is more globally neuroprotective. These results extend
      knowledge of the physiological roles of huntingtin, facilitating development of
      HD therapeutics.

PMID- 25575959
TI  - Longitudinal metabolite changes in Huntington's disease during disease onset.
AB  - BACKGROUND: Previous cross-sectional magnetic resonance spectroscopy (MRS)
      studies in Huntington's disease (HD) have demonstrated differences in metabolite
      concentrations in several regions of interest, especially the putamen and caudate
      nucleus. OBJECTIVE: To assess metabolite changes in both premanifest and early HD
      over a two year follow up period using MRS at 7 Tesla in several regions of
      interest. METHODS: In 13 HD gene carriers (10 premanifest and 3 manifest HD)
      proton MRS was performed at baseline and after 24 months. At follow up, four of
      the premanifest HD gene carriers had progressed into manifest HD, as assessed by
      clinical measures. 7T MR proton spectroscopy was performed in three regions of
      interest; the caudate nucleus, putamen and prefrontal cortex. Six metabolites
      were quantified for each region at each time point. Statistical analysis was
      performed using Wilcoxon signed rank tests. RESULTS: Across all subjects, a
      longitudinal decrease in the caudate nucleus in creatine (p = 0.038) and myo
      inositol (p = 0.015) concentrations was found. A significant decrease in the
      putamen was seen in the total N-acetylaspartate (tNAA) (p = 0.028) and choline
      concentrations (p = 0.028). For premanifest HD converters, a non-significant high
      rate of tNAA decrease in the putamen was found compared to non-converting
      premanifest HD. CONCLUSION: Over a two year period we have demonstrated
      metabolite changes in the caudate nucleus and putamen of HD gene carriers around
      disease onset. This demonstrates the potential of MRS for providing a biomarker
      of disease progression and for evaluating future therapeutic interventions.

PMID- 25575960
TI  - Presymptomatic glutamate levels in prefrontal cortex in the Hdh(CAG150) mouse
      model of Huntington's disease.
AB  - BACKGROUND: Huntington's disease (HD) is a genetic neurodegenerative disorder
      with few available treatments. Clinical observations suggest prefrontal
      dysfunction in early stages of HD is associated with altered glutamate transport.
      Evidence from the R6/2 mouse model suggests an abnormal increase in glutamate
      signaling in the sensorimotor cortex and striatum. OBJECTIVE: The present study
      was designed to determine if a similar deficit in glutamate function occurs in
      the prefrontal cortex (PFC) of Hdh(CAG150) mice. METHODS: We used the following
      groups of 40 week old male and female Hdh(CAG150) mice: homozygote n = 7,
      heterozygote n = 7, wild type n = 6. Motor coordination was evaluated using a
      hanging wire grid test and a balance beam. Microdialysis measurements were taken
      from the PFC of freely moving mice while glutamate transporters were inhibited by
      L-trans-pyrrolidine-2, 4-dicarboxylate (PDC) and compared to baseline glutamate
      levels. RESULTS: RESULTS indicated an elevation in glutamate levels in response
      to PDC but no significant difference among genotype groups. When comparing wild
      type and homozygote alone, a significant difference in total extracellular
      glutamate was observed. Contrary to our original hypothesis, the homozygote group
      had lower glutamate levels compared to their wild type counterparts. Furthermore,
      there was a significant difference in GABA measurements across genotypes.
      CONCLUSIONS: Our results suggest a mechanistic dichotomy between R6/2 and
      Hdh(CAG150) mice and underscores the need to select the appropriate HD mouse
      model when assessing therapeutic interventions. In particular, the time when
      animals are evaluated can have a significant impact on behavioral and
      physiological measures and so should be carefully considered.

PMID- 25575961
TI  - Application of the 2012 Systemic Lupus International Collaborating Clinics
      classification criteria to patients in a regional Swedish systemic lupus
      erythematosus register.
AB  - INTRODUCTION: In 2012, the Systemic Lupus International Collaborating Clinics
      (SLICC) network presented a new set of criteria (SLICC-12) to classify systemic
      lupus erythematosus (SLE). The present study is the first to evaluate the
      performance of SLICC-12 in an adult European study population. Thus, SLICC-12
      criteria were applied to confirmed SLE cases in our regional SLE register as well
      as to individuals with a fair suspicion of systemic autoimmune disease who were
      referred to rheumatology specialists at our unit. METHODS: We included 243
      confirmed SLE patients who met the 1982 American College of Rheumatology (ACR-82)
      classification criteria and/or the Fries 'diagnostic principle' (presence of
      antinuclear antibodies on at least one occasion plus involvement of at least two
      defined organ systems) and 55 controls with possible systemic autoimmune disease,
      including the presence of any SLE-related autoantibody. RESULTS: SLICC-12 showed
      a diagnostic sensitivity of 94% (95% confidence interval (CI), 0.90 to 0.96)
      compared with 90% (95% CI, 0.85 to 0.93) for the updated set of ACR criteria from
      1997 (ACR-97), whereas ACR-82 failed to identify every fifth true SLE case.
      However, the disease specificity of SLICC-12 reached only 74% (95% CI, 0.60 to
      0.84) and did not change much when involvement of at least two different organs
      was required as an indicator of systemic disease. In addition, SLICC-12
      misclassified more of the controls compared to ACR-82, ACR-97 and Fries.
      CONCLUSIONS: Establishing a standard definition of SLE continues to challenge
      lupus researchers and clinicians. We confirm that SLICC-12 has advantages with
      regard to diagnostic sensitivity, whereas we found the diagnostic specificity to
      be surprisingly low. To accomplish increased sensitivity and specificity figures,
      a combination of criteria sets for clinical SLE studies should be considered.

PMID- 25575962
TI  - Bone geometry on the contact stress in the shoulder for evaluation of pressure
      ulcers: finite element modeling and experimental validation.
AB  - This research presents the finite element modeling (FEM) of human-specific
      computed tomography (CT) data to study the effect of bone prominences on contact
      stress in the shoulder for prevention of pressure ulcers. The 3D geometry of
      scapula, skin, and surrounding soft tissues in the shoulder was reconstructed
      based on the anonymous CT data of a human subject in a prone posture (without
      loading on the shoulder) for FEM analysis of the contact stress. FEM analysis
      results show that the maximum stress is located at the prominence of the scapula
      with sharp bone geometry. This demonstrates that stress concentration at the bone
      prominence is a significant factor to cause the high contact stress, which is a
      source for pressure ulcers. For experimental validation, a physical shoulder
      model manufactured by 3D printing of the bone geometry and the mold for molding
      of tissue-mimicking silicone was developed. Compression tests of the mattress
      foam and silicone were conducted to find the nonlinear stress-strain relations as
      inputs for FEM. Experiments of compressing the shoulder model against the foam
      were carried out. Three flexible force sensors were embedded inside the model to
      measure the contact forces and compared to the FEM predictions. Results show that
      the FEM predicted forces match well with the experimental measurements and
      demonstrate that FEM can accurately predict the stress distributions in the
      shoulder to study the effect of bone geometry on the inception of pressure
      ulcers. 

PMID- 25575963
TI  - The reactivity of well-dispersed zerovalent iron nanoparticles toward
      pentachlorophenol in water.
AB  - In order to prevent the aggregation of nanoparticles (NPs), surface modification
      or the addition of a stabilizer are used for stabilization. However, the real
      reactivity of NPs is still unclear because of the surface coating. For different
      physical dispersion methods, the particle stabilization for nanoscale zerovalent
      iron (NZVI) particles and their reactivity are studied. The particle properties
      of different preparations and their reactivity toward one polychlorinated
      aromatic compound, pentachlorophenol (PCP), with different electrolytes are also
      evaluated. Ultrasonication (US) with magnetic stirring disperses NZVI and Pd/Fe
      NPs well in water and does not affect the surface redox property a lot under the
      operating conditions in this study. The well-suspended NZVI cannot dechlorinate
      PCP but adsorption removal is observed. Compared to shaking, which gives limited
      removal of PCP (about 43%), Pd/Fe NPs remove 81% and 93% of PCP from water in the
      US and the US/stirring systems, respectively, which demonstrates that a greater
      surface area is exposed because of effective dispersion of Pd/Fe NPs. As the Pd
      doping increases, the dechlorination kinetics of PCP is improved, which shows
      that a catalyst is needed. With US/stirring, chloride ions do not significantly
      affect the removal kinetics of PCP, but the removal efficiency increases in the
      presence of nitrate ions because PCP anions were adsorbed and coagulated by the
      greater amount of iron (hydro)oxides that are generated from the reduction of
      nitrate on Pd/Fe. However, bicarbonate ions significantly block the adsorption
      and reaction sites on the Pd/Fe NP surface with US/stirring. The US/stirring
      method can be used to evaluate the actual activity of NPs near the nanoscale. The
      use of Pd/Fe NPs with US/stirring removes PCP from water effectively, even in the
      presence of common anions expect a high concentration of bicarbonate. 

PMID- 25575964
TI  - Effect of PPARdelta agonist on stearoyl-CoA desaturase 1 in human pancreatic
      cancer cells: role of MEK/ERK1/2 pathway.
AB  - OBJECTIVE: The stearoyl-CoA desaturase 1 (SCD1), also known as Delta9-desaturase,
      is a regulatory enzyme in the cellular lipid modification process that has been
      linked to pancreatic cancer and diabetes. The aim of the present study was to
      investigate the effect of peroxisome proliferative-activated receptor delta
      (PPARdelta) agonist and ERK1/2- and EGF receptor (EGFR)-dependent pathways on the
      expression of SCD1 in human pancreatic carcinoma cell line PANC-1. METHODS: PANC
      1 cells cultured in RPMI-1640 were exposed to the commonly used MEK inhibitor
      PD98059, EGFR-selective inhibitor AG1478, and PPARdelta agonist GW0742. Changes
      in mRNA, protein expression and activity index of SCD1 were then determined using
      real-time reverse transcription polymerase chain reaction, Western blot and gas
      liquid chromatography, respectively. RESULTS: The activity index and expression
      of SCD1 (p<0.01) decreased following treatment with PPARdelta agonist at both
      mRNA and protein levels, whereas significant increases were observed after
      treatment with MEK or EGFR inhibitor. It was also found that the activity index
      of SCD1 were lower (p<0.01) in the combined treatment compared to the incubation
      with either inhibitor alone. CONCLUSIONS: PPARdelta and MEK/ERK1/2- and EGFR
      dependent pathways affect the expression and activity of SCD1 in pancreatic
      cancer cells. Furthermore, the aforementioned kinase signalling pathways were
      involved in an inhibitory effect on the expression and activity of SCD1 in these
      cells, possibly via PPARdelta activation.

PMID- 25575965
TI  - Spatial analysis of paediatric swimming pool submersions by housing type.
AB  - OBJECTIVE: Drowning is a major cause of unintentional childhood death. The
      relationship between childhood swimming pool submersions, neighbourhood
      sociodemographics, housing type and swimming pool location was examined in Harris
      County, Texas. STUDY DESIGN AND SETTING: Childhood pool submersion incidents were
      examined for spatial clustering using the Nearest Neighbor Hierarchical Cluster
      (Nnh) algorithm. To relate submersions to predictive factors, an Markov Chain
      Monte Carlo (MCMC) Poisson-Lognormal-Conditional Autoregressive (CAR) spatial
      regression model was tested at the census tract level. RESULTS: There were 260
      submersions; 49 were fatal. Forty-two per cent occurred at single-family
      residences and 36% at multifamily residential buildings. The risk of a submersion
      was 2.7 times higher for a child at a multifamily than a single-family residence
      and 28 times more likely in a multifamily swimming pool than a single family
      pool. However, multifamily submersions were clustered because of the
      concentration of such buildings with pools. Spatial clustering did not occur in
      single-family residences. At the tract level, submersions in single-family and
      multifamily residences were best predicted by the number of pools by housing type
      and the number of children aged 0-17 by housing type. CONCLUSIONS: Paediatric
      swimming pool submersions in multifamily buildings are spatially clustered. The
      likelihood of submersions is higher for children who live in multifamily
      buildings with pools than those who live in single-family homes with pools.

PMID- 25575966
TI  - Insights into osteoarthritis progression revealed by analyses of both knee
      tibiofemoral compartments.
AB  - OBJECTIVE: To identify disease relevant genes and pathways associated with knee
      Osteoarthritis (OA) progression in human subjects using medial and lateral
      compartment dominant OA knee tissue. DESIGN: Gene expression of knee cartilage
      was comprehensively assessed for three regions of interest from human medial
      dominant OA (n = 10) and non-OA (n = 6) specimens. Histology and gene expression
      were compared for the regions with minimal degeneration, moderate degeneration
      and significant degeneration. Agilent whole-genome microarray was performed and
      data were analyzed using Agilent GeneSpring GX11.5. Significant differentially
      regulated genes were further investigated by Ingenuity Pathway Analysis (IPA) to
      identify functional categories. To confirm their association with disease
      severity as opposed to site within the knee, 30 differentially expressed genes,
      identified by microarray, were analyzed by quantitative reverse-transcription
      polymerase chain reaction on additional medial (n = 16) and lateral (n = 10)
      compartment dominant knee OA samples. RESULTS: A total of 767 genes were
      differentially expressed >= two-fold (P <= 0.05) in lesion compared to relatively
      intact regions. Analysis of these data by IPA predicted biological functions
      related to an imbalance of anabolism and catabolism of cartilage matrix
      components. Up-regulated expression of IL11, POSTN, TNFAIP6, and down-regulated
      expression of CHRDL2, MATN4, SPOCK3, VIT, PDE3B were significantly associated
      with OA progression and validated in both medial and lateral compartment dominant
      OA samples. CONCLUSIONS: Our study provides a strategy for identifying targets
      whose modification may have the potential to ameliorate pathological alternations
      and progression of disease in cartilage and to serve as biomarkers for
      identifying individuals susceptible to progression.

PMID- 25575967
TI  - The relation of MRI-detected structural damage in the medial and lateral
      patellofemoral joint to knee pain: the Multicenter and Framingham Osteoarthritis
      Studies.
AB  - OBJECTIVE: To examine the relation of cartilage loss and bone marrow lesions
      (BMLs) in the medial and lateral patellofemoral joint (PFJ) to knee pain.
      METHODS: We categorized the location of full-thickness cartilage loss and BMLs in
      the PFJ on knee magnetic resonance imaging (MRIs) from the Multicenter
      Osteoarthritis (MOST) and Framingham Osteoarthritis (FOA) Studies as no damage,
      isolated medial, isolated lateral, or both medial and lateral (mixed). We
      determined the relation of MRI lesions in each PFJ region to prevalent knee pain.
      Differences in knee pain severity were compared among categories of PFJ full
      thickness cartilage loss and BMLs using quantile regression. RESULTS: In MOST (n
      = 1137 knees), compared with knees without full-thickness cartilage loss, knees
      with isolated lateral or mixed PFJ full-thickness cartilage loss had 1.9 (1.3,
      2.8) and 1.9 (1.2, 2.9) times the odds of knee pain, respectively, while isolated
      medial cartilage loss had no association with knee pain. BMLs in both the medial
      and lateral PFJ had 1.5 (1.1, 2.0) times the odds of knee pain compared with
      knees without BMLs. Knee pain severity was lowest in knees with isolated medial
      PFJ cartilage loss or BMLs. In FOA (n = 934 knees), neither isolated medial nor
      lateral cartilage loss was associated with knee pain, whereas isolated BMLs in
      either region were associated with pain. CONCLUSIONS: Results were not completely
      concordant but suggest that knee pain risk and severity is greatest with
      cartilage loss isolated to (MOST) or inclusive of (MOST and FOA) the lateral PFJ.
      While BMLs in either the medial or lateral PFJ are related to pain.

PMID- 25575968
TI  - A chondrocyte infiltrated collagen type I/III membrane (MACI(r) implant) improves
      cartilage healing in the equine patellofemoral joint model.
AB  - Autologous chondrocyte implantation (ACI) has improved outcome in long-term
      studies of joint repair in man. However, ACI requires sutured periosteal flaps to
      secure the cells, which precludes minimally-invasive implantation, and introduces
      complications with arthrofibrosis and graft hypertrophy. This study evaluated ACI
      on a collagen type I/III scaffold (matrix-induced autologous chondrocyte
      implantation; MACI((r))) in critical sized defects in the equine model. METHODS:
      Chondrocytes were isolated from horses, expanded and seeded onto a collagen I/III
      membrane (ACI-MaixTM) and implanted into one of two 15-mm defects in the femoral
      trochlear ridge of six horses. Control defects remained empty as ungrafted
      debrided defects. The animals were examined daily, scored by second look
      arthroscopy at 12 weeks, and necropsy examination 6 months after implantation.
      Reaction to the implant was determined by lameness, and synovial fluid
      constituents and synovial membrane histology. Cartilage healing was assessed by
      arthroscopic scores, gross assessment, repair tissue histology and
      immunohistochemistry, cartilage glycosaminoglycan (GAG) and DNA assay, and
      mechanical testing. RESULTS: MACI((r)) implanted defects had improved
      arthroscopic second-look, gross healing, and composite histologic scores,
      compared to spontaneously healing empty defects. Cartilage GAG and DNA content in
      the defects repaired by MACI implant were significantly improved compared to
      controls. Mechanical properties were improved but remained inferior to normal
      cartilage. There was minimal evidence of reaction to the implant in the synovial
      fluid, synovial membrane, subchondral bone, or cartilage. CONCLUSIONS: The
      MACI((r)) implant appeared to improve cartilage healing in a critical sized
      defect in the equine model evaluated over 6 months.

PMID- 25575969
TI  - Change in the plasmid copy number in acetic acid bacteria in response to growth
      phase and acetic acid concentration.
AB  - Plasmids pGE1 (2.5 kb), pGE2 (7.2 kb), and pGE3 (5.5 kb) were isolated from
      Gluconacetobacter europaeus KGMA0119, and sequence analyses revealed they
      harbored 3, 8, and 4 genes, respectively. Plasmid copy numbers (PCNs) were
      determined by real-time quantitative PCR at different stages of bacterial growth.
      When KGMA0119 was cultured in medium containing 0.4% ethanol and 0.5% acetic
      acid, PCN of pGE1 increased from 7 copies/genome in the logarithmic phase to a
      maximum of 12 copies/genome at the beginning of the stationary phase, before
      decreasing to 4 copies/genome in the late stationary phase. PCNs for pGE2 and
      pGE3 were maintained at 1-3 copies/genome during all phases of growth. Under a
      higher concentration of ethanol (3.2%) the PCN for pGE1 was slightly lower in all
      the growth stages, and those of pGE2 and pGE3 were unchanged. In the presence of
      1.0% acetic acid, PCNs were higher for pGE1 (10 copies/genome) and pGE3 (6
      copies/genome) during the logarithmic phase. Numbers for pGE2 did not change,
      indicating that pGE1 and pGE3 increase their PCNs in response to acetic acid.
      Plasmids pBE2 and pBE3 were constructed by ligating linearized pGE2 and pGE3 into
      pBR322. Both plasmids were replicable in Escherichia coli, Acetobacter
      pasteurianus and G. europaeus, highlighting their suitability as vectors for
      acetic acid bacteria. 

PMID- 25575970
TI  - Prospecting cold deserts of north western Himalayas for microbial diversity and
      plant growth promoting attributes.
AB  - Microbial communities in different samples collected from cold deserts of north
      western Himalayas, India, were analyzed using 16S rRNA gene sequencing and
      phospholipid fatty acids (PLFA) analysis. A total of 232 bacterial isolates were
      characterized employing 16S rDNA-Amplified Ribosomal DNA Restriction Analysis
      with the three restriction endonucleases Alu I, Msp I and Hae III, which led to
      formation of 29-54 groups for the different sites, adding up to169 groups. 16S
      rRNA gene based phylogenetic analysis, revealed that 82 distinct species of 31
      different genera, belonged to four phyla Actinobacteria, Bacteroidetes,
      Firmicutes and Proteobacteria. PLFA profiling was performed for concerned samples
      which gave an estimate of microbial communities without cultivating the
      microorganisms. PLFA analysis led to characterization of diverse group of
      microbes in different samples such as gram-negative, gram-positive bacteria,
      actinomycetes, cyanobacteria, anaerobic bacteria, sulphate reducing bacteria and
      fungi. The representative strains were screened for their plant growth promoting
      attributes, which included production of ammonia, HCN, gibberellic acid, IAA and
      siderophore; solubilization of phosphorus and activity of ACC deaminase. In vitro
      antifungal activity assay was performed against Rhizoctonia solani and
      Macrophomina phaseolina. Cold adapted microorganisms may serve as inoculants for
      crops growing under cold climatic conditions. To our knowledge, this is the first
      report for the presence of Arthrobacter nicotianae, Brevundimonas terrae,
      Paenibacillus tylopili and Pseudomonas cedrina in cold deserts and exhibit
      multifunctional PGP attributes at low temperatures. 

PMID- 25575971
TI  - Production of biodiesel from vegetable oil and microalgae by fatty acid
      extraction and enzymatic esterification.
AB  - The aim of this work was to obtain biodiesel (methyl esters) from the
      saponifiable lipids (SLs) fraction of the microalga Nannochloropsis gaditana,
      whose biomass dry weight contains 12.1 wt% of these lipids. SLs were extracted
      from the microalga as free fatty acids (FFAs) for subsequent transformation to
      methyl esters (biodiesel) by enzymatic esterification. Extraction as FFAs rather
      than as SLs allows them to be obtained with higher purity. Microalgal FFAs were
      obtained by direct saponification of lipids in the biomass and subsequent
      extraction-purification with hexane. Esterification of FFAs with methanol was
      catalysed by lipase Novozym 435 from Candida antarctica. Stability studies of
      this lipase in the operational conditions showed that the esterification degree
      (ED) attained with the same batch of lipase remained constant over six reaction
      cycles (36 h total reaction time). The optimal conditions attained for 4 g of
      FFAs were 25 degrees C, 200 rpm, methanol/FFA molar ratio of 1.5:1, Novozym
      435/FFA ratio of 0.025:1 w/w and 4 h reaction time. In these conditions the ED
      attained was 92.6%, producing a biodiesel with 83 wt% purity from microalgal
      FFAs. Several experimental scales were tested (from 4 to 40 g FFAs), and in all
      cases similar EDs were obtained.

PMID- 25575972
TI  - Faster in vivo clearance of human embryonic kidney than Chinese hamster ovary
      cell derived protein: Role of glycan mediated clearance.
AB  - This investigation used in vivo and in vitro tools to study pharmacokinetics and
      glycosylation of two monomeric antibodies produced either transiently by HEK293
      cells or stably by Chinese hamster ovary cells, and demonstrated that higher in
      vivo clearance of human embryonic kidney antibody was due to higher
      glycosylation, thus higher mannose receptor mediated uptake. 

PMID- 25575973
TI  - The impact of abdominal aortic aneurysm on muscle mass and energy expenditure: A
      novel preliminary investigation.
AB  - OBJECTIVE: Vascular surgical patients, including those with abdominal aortic
      aneurysm (AAA), are nutritionally vulnerable. The aim of this study was to
      compare resting energy expenditure (REE) of patients with AAA relative to age-
      and gender-matched controls and explore relationships between aneurysm size and
      muscle mass. METHODS: Twenty patients with AAA underwent assessment of REE using
      indirect calorimetry. Mid-arm circumference and triceps skinfold thickness were
      measured and corrected arm muscle area calculated. Twenty gender- and age-matched
      controls were assessed using the same procedures. RESULTS: Mean (SD) age of
      participants with AAA was 74.7 (7.7) years, size of AAA ranged from 45 to 70 mm.
      Median (IQR) REE was significantly higher than controls [5990 (5469, 7017) kJ/day
      versus 5086 (4536, 5886) kJ/day, p = .011; or 69 (64, 80) kJ/kg/day versus 66
      (61, 69) kJ/kg/day, p = .046]. While weight-adjusted REE was independent of
      aneurysm size (r = .200; p = .397), as aneurysm size increased, weight-adjusted
      corrected arm muscle area decreased (r = -.576; p = .008). CONCLUSION: The raised
      REE and decline in muscle mass associated with larger AAA suggest that early
      detection and attention to nutritional requirements of patients with AAA may be
      warranted.

PMID- 25575974
TI  - Epidemiology and treatment strategies of iliac vein thrombophlebitis.
AB  - INTRODUCTION: This study aimed to determine the epidemiology of iliac vein
      thrombophlebitis and describe gender differences associated with the management
      of this pathology. METHODS: The 2010 National Inpatient Sample was
      retrospectively reviewed to include all inpatients with ICD-9 codes identifying
      iliac vein thrombophlebitis (451.81). Demographics, disposition, anticoagulation,
      thrombolytics, stent placement, open operative intervention, complications (deep
      vein thrombosis/pulmonary embolism), and mortality rates were reported.
      Statistical analysis included descriptive statistics and Student's t-testing with
      P < 0.05 deemed significant. RESULTS: The incidence of iliac vein
      thrombophlebitis was 1/1,000,000 people. Men had an average age of 48 +/- 20
      years and women were significantly older at 59 +/- 18 years (P = 0.02). There
      were no differences in treatment strategies or rates of complications between men
      and women including pulmonary embolism (23% for males, 16% of females) and deep
      vein thrombosis (29% for males and 19% for females). Length of stay between
      groups was not significant (11 +/- 20 days for males and 7.7 +/- 6 days for
      females). Overall mortality was 1.5%. CONCLUSION: Iliac vein thrombophlebitis is
      a rare disease. Females who develop iliac vein thrombophlebitis are significantly
      older than their male counterparts. The rates of deep vein thrombosis, pulmonary
      embolism, and interventional strategies are not different between the sexes.

PMID- 25575975
TI  - Evaluating outcomes of alternative dosing strategies for cefepime: a qualitative
      systematic review.
AB  - OBJECTIVE: To perform a qualitative systematic review of the evidence comparing
      traditional with prolonged intermittent or continuous infusions of cefepime based
      on clinical and pharmacodynamic outcomes. DATA SOURCES: PubMed (1946 to October
      2014), EMBASE (1980 to October 2014), CENTRAL, Cochrane Database of Systematic
      Reviews, Web of Science, and International Pharmaceutical Abstracts (1970 to
      October 2014) were searched using the terms cefepime, pharmacokinetics,
      pharmacodynamics, drug administration, intravenous infusions, intravenous drug
      administration, continuous infusion, extended infusion, and intermittent therapy.
      Reference lists from relevant materials were reviewed. STUDY SELECTION AND DATA
      EXTRACTION: Articles evaluating administration regimens of cefepime, one of which
      included the traditional, manufacturer-recommended 0.5-hour infusion and the
      other a prolonged or continuous infusion were included. Prespecified clinical
      outcomes of interest included all-cause mortality, length of hospital stay,
      clinical cure, and adverse events. The primary pharmacodynamic outcome was
      percentage time of unbound drug concentration remaining above the minimum
      inhibitory concentration. DATA SYNTHESIS: In all, 18 studies were included; 6
      studies assessed clinical outcomes, and 12 assessed pharmacodynamic outcomes.
      Prolonged or continuous infusions of cefepime achieved the pharmacodynamic
      targets more often than traditional infusions. The association of improved
      clinical outcomes with prolonged or continuous infusions is unclear. All-cause
      mortality was significantly decreased with the use of a prolonged cefepime
      infusion in a retrospective study. Two prospective, randomized studies
      demonstrated no statistically significant difference in mortality between
      prolonged and intermittent infusions. CONCLUSIONS: The available literature on
      prolonged and continuous infusions of cefepime demonstrated an improved
      achievement of pharmacodynamic targets; however, the effect on clinical outcomes
      is inconclusive. Well-designed prospective studies are required to determine
      optimal dosing and administration strategies.

PMID- 25575976
TI  - High-grade acute organ toxicity and p16(INK4A) expression as positive prognostic
      factors in primary radio(chemo)therapy for patients with head and neck squamous
      cell carcinoma.
AB  - BACKGROUND: Superior treatment response and survival for patients with human
      papilloma virus (HPV)-positive head and neck cancer (HNSCC) are documented in
      clinical studies. However, the relevance of high-grade acute organ toxicity
      (HGAOT), which has also been correlated with improved prognosis, has attracted
      scant attention in HPV-positive HNSCC patients. Hence we tested the hypothesis
      that both parameters, HPV and HGAOT, are positive prognostic factors in patients
      with HNSCC treated with definite radiotherapy (RT) or radiochemotherapy (RCT).
      PATIENTS AND METHODS: Pretreatment tumor tissue and clinical records were
      available from 233 patients receiving definite RT (62 patients) or RCT (171
      patients). HPV infection was analysed by means of HPV DNA detection or p16(INK4A)
      expression; HGAOT was defined as the occurrence of acute organ toxicity >grade 2
      according to the Common Toxicity Criteria. Both variables were correlated with
      overall survival (OS) using Cox proportional hazards regression. RESULTS:
      Positivity for HPV DNA (44 samples, 18.9 %) and p16(INK4A) expression (102
      samples, 43.8 %) were significantly correlated (p < 0.01), and HGAOT occurred in
      77 (33 %) patients. Overall, the 5-year OS was 23 %; stratified for p16(INK4A)
      expression and HGAOT, OS rates were 47 %, 42 %, 20 % and 10 % for patients with
      p16(INK4A) expression and HGAOT, patients with HGAOT only, patients with
      p16(INK4A) expression only, and patients without p16(INK4A) expression or HGAOT,
      respectively. After multivariate testing p16(INK4A) expression (p = 0.003) and
      HGAOT (p < 0.001) were significantly associated with OS. CONCLUSION: P16(INK4A)
      expression and HGAOT are independent prognostic factors for OS of patients with
      HNSCC, whereas p16(INK4A) expression is particularly important for patients
      without HGAOT.

PMID- 25575977
TI  - Treatment of acromegaly patients with risk-adapted single or fractionated
      stereotactic high-precision radiotherapy: High local control and low toxicity in
      a pooled series.
AB  - PURPOSE: The purpose of this work was to evaluate a prospectively initiated two
      center protocol of risk-adapted stereotactic radiosurgery (SRS) or stereotactic
      radiotherapy (SRT) in patients with acromegaly. PATIENTS AND METHODS: In total 35
      patients (16 men/19 women, mean age 54 years) were prospectively included in a
      treatment protocol of SRS [planning target volume (PTV < 4 ccm, > 2 mm to optic
      pathways = low risk] or SRT (PTV >= 4 ccm, <= 2 mm to optic pathways = high
      risk). The mean tumor volume was 3.71 ccm (range: 0.11-22.10 ccm). Based on the
      protocol guidelines, 21 patients were treated with SRS and 12 patients with SRT,
      2 patients received both consecutively. RESULTS: The median follow-up (FU)
      reached 8 years with a 5-year overall survival (OS) of 87.3% [confidence interval
      (CI): 70.8-95.6%] and 5-year local control rate of 97.1% (CI: 83.4-99.8%). Almost
      80% (28/35) presented tumor shrinkage during FU. Endocrinological cure was
      achieved in 23% and IGF-1 normalization with reduced medication was achieved in
      40% of all patients. An endocrinological response was generally achieved within
      the first 3 years, but endocrinological cure can require more than 8 years. A new
      adrenocorticotropic hypopituitarism occurred in 13 patients (46.4%). A new visual
      field disorder and a new oculomotor palsy occurred in 1 patient, respectively.
      Patients with occurrence of visual/neurological impairments had a longer FU (p =
      0.049). CONCLUSION: Our SRS/SRT protocol proved to be safe and successful in
      terms of tumor control and protection of the visual system. The timing and rate
      of endocrine improvements are difficult to predict. One has to accept an
      unavoidable rate of additional adrenocorticotropic hypopituitarism in the long
      term.

PMID- 25575978
TI  - The SS x-ray unit as an instrument for "total registration" and "race selection".
AB  - OBJECTIVES: The aim of this article is to show that, after the onset of World War
      II at the latest, the central task of the x-ray unit of the Nazi-SS
      (Schutzstaffel) led by Prof. Hans Holfelder was by no means the early diagnosis
      of tuberculosis. Its primary purpose, rather, was to serve the various "racial"
      and inhuman aims of the SS itself. METHODS: Main historical sources and
      information about the SS x-ray unit are surveyed and analyzed. RESULTS: Clearly,
      the significance of the x-ray storm unit was increasingly subordinated to the
      necessities of the war until its original objectives disappeared from focus
      completely. The main purpose of operation of the x-ray storm unit thus by no
      means lay in the early detection of tuberculosis and did not therefore serve
      tuberculosis control. CONCLUSION: The actual objective lay, rather, in the
      implementation of SS aims in terms of Volk politics, genetics, and "racial
      hygiene".

PMID- 25575979
TI  - Successful radiation treatment of chylous ascites following
      pancreaticoduodenectomy.
AB  - Chylous ascites is a rare complication following pancreaticoduodenectomy. We
      report on a case of chylous ascites following pancreaticoduodenectomy in a 76
      year-old patient diagnosed with pancreatic cancer. There are various known
      conservative management strategies, including dietary measures or total
      parenteral nutrition. Unfortunately, conservative treatment-with total parenteral
      nutrition and fasting over a period of 4 weeks-was not successful in the present
      case. The daily output volume of chylous ascites was up to 2500 ml/day. Based on
      clinical experiences with successfully treated lymphocutaneous fistulas, low-dose
      radiotherapy was initiated. External beam radiotherapy comprising a total dose of
      8.0 Gy to the paraaortic lymph node region was administered in daily single
      fractions of 1.0 Gy (five fractions/week). Throughout the course of external beam
      radiotherapy, the secretion of abdominal ascites rapidly decreased, resulting in
      complete resolution after 2 weeks. There was no clinical evidence of chylous
      ascites on follow-up. As a result of this experience, we believe that external
      beam radiotherapy should be considered as an alternative therapy in refractory
      cases of chylous ascites. 

PMID- 25575980
TI  - Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma
      cell lines.
AB  - BACKGROUND AND PURPOSE: Cafestol is a diterpene molecule found in coffee beans
      and has anticarcinogenic properties. The aim of the study was to examine the
      effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells.
      MATERIALS AND METHODS: Three HNSCC cell lines (SCC25, CAL27 and FaDu) were
      treated with increasing doses of cafestol. Then combination experiments with
      cisplatin and irradiation were carried out. Drug interactions and possible
      synergy were calculated using the combination index analysis. Clonogenic assays
      were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the
      rate of apoptosis was measured with flow cytometry. RESULTS: Treatment of HNSCC
      cells with cafestol leads to a dose-dependent reduction of cell viability and to
      induction of apoptosis. Combination with irradiation shows a reduction of
      clonogenic survival compared to each treatment method alone. In two of the cell
      lines a significant additive effect was observed. CONCLUSION: Cafestol is a
      naturally occurring effective compound with growth-inhibiting properties in head
      and neck cancer cells. Moreover, it leads to a significant inhibition of colony
      formation.

PMID- 25575981
TI  - Reirradiation for recurrent head and neck cancer with salvage interstitial pulsed
      dose-rate brachytherapy: Long-term results.
AB  - PURPOSE: To assess the long-term results of protocol-based interstitial pulsed
      dose-rate (PDR) brachytherapy as reirradiation combined with simultaneous
      chemotherapy and interstitial hyperthermia in selected patients with recurrent
      head and neck tumors. MATERIALS AND METHODS: A total of 104 patients with biopsy
      proven recurrent head and neck cancer were treated with interstitial PDR
      brachytherapy. Salvage surgery had also been undergone by 53/104 (51%) patients
      (R1 or R2 resection in > 80% of patients). Salvage brachytherapy alone was
      administered in 81 patients (78%), with a median total dose of 56.7 Gy. Salvage
      brachytherapy in combination with external beam radiotherapy (EBRT) was performed
      in 23/104 patients (32%), using a median total dose of DREF = 24 Gy.
      Simultaneously to PDR brachytherapy, concomitant chemotherapy was administered in
      58/104 (55.8%) patients. A single session of interstitial hyperthermia was also
      used to treat 33/104 (31.7%) patients. The analysis was performed after a median
      follow-up of 60 months. RESULTS: Calculated according to Kaplan-Meier, local
      tumor control rates after 2, 5, and 10 years were 92.5, 82.4, and 58.9%,
      respectively. Comparing results of salvage PDR brachytherapy with or without
      simultaneous chemotherapy, the 10-year local control rates were 76 vs. 39% (p =
      0014), respectively. No other patient- or treatment-related parameters had a
      significant influence on treatment results. Soft tissue necrosis or bone necrosis
      developed in 18/104 (17.3%) and 11/104 (9.6%) patients, respectively, but only 3%
      of patients required surgical treatment. CONCLUSION: PDR interstitial
      brachytherapy with simultaneous chemotherapy is a very effective and, in
      experienced hands, also a safe treatment modality in selected patients with head
      and neck cancer in previously irradiated areas.

PMID- 25575983
TI  - Silodosin: a review of its use in the treatment of the signs and symptoms of
      benign prostatic hyperplasia.
AB  - Silodosin is a highly selective alpha1A-adrenoceptor antagonist indicated for the
      treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Oral
      silodosin had a rapid onset of effect in men with lower urinary tract symptoms
      (LUTS) associated with BPH, with improvements seen in voiding and storage
      symptoms, maximum urinary flow rate and health-related quality of life in well
      designed, 12-week trials. Silodosin was noninferior to tamsulosin in terms of
      improving LUTS associated with BPH. The efficacy of silodosin was maintained in 9
      month extension studies and was also seen in a phase IV study conducted in a real
      world setting. Silodosin was generally well tolerated and was associated with a
      low risk of orthostatic hypotension. Abnormal ejaculation was the most commonly
      reported adverse event, although few patients discontinued treatment with
      silodosin because of this adverse event. In conclusion, silodosin is a useful
      option for the treatment of LUTS associated with BPH. 

PMID- 25575982
TI  - Evolutionary conservation of the CDK targets in eukaryotic DNA replication
      initiation.
AB  - A fundamental requirement for all organisms is the faithful duplication and
      transmission of the genetic material. Failure to accurately copy and segregate
      the genome during cell division leads to loss of genetic information and
      chromosomal abnormalities. Such genome instability is the hallmark of the
      earliest stages of tumour formation. Cyclin-dependent kinase (CDK) plays a vital
      role in regulating the duplication of the genome within the eukaryotic cell
      cycle. Importantly, this kinase is deregulated in many cancer types and is an
      emerging target of chemotherapeutics. In this review, I will consider recent
      advances concerning the role of CDK in replication initiation across eukaryotes.
      The implications for strict CDK-dependent regulation of genome duplication in the
      context of the cell cycle will be discussed. 

PMID- 25575984
TI  - A Handy EEG Electrode Set for patients suffering from altered mental state.
AB  - Although electroencephalography (EEG) is an important diagnostic tool for
      investigating patients with unexplained altered mental state (AMS), recording of
      emergency EEG is not a clinical routine. This is mainly due to the cumbersome
      electrode solutions. A Handy EEG Electrode Set consists of ten EEG, two EOG, two
      ground and two commutative reference hydrogel-coated silver wire electrodes
      attached to a thin polyester carrier film. The clinical usefulness of the Handy
      EEG Electrode Set was tested in 13 patients (five females, eight males) with AMS.
      EEG recordings were conducted at the same time with a standard 10-20 electrode
      set. The registration in the first patient case without the behind-ear electrodes
      (T9 and T10), indicated that these electrodes are very crucial to provide
      clinically relevant information from posterior regions of brain. In following 12
      cases, the sensitivity and specificity for detecting EEG abnormality based on the
      Handy EEG Electrode Set recordings were 83 and 100 %, respectively. The Handy EEG
      Electrode Set proved to be easy to use and to provide valuable information for
      the neurophysiological evaluation of a patient suffering from AMS. However,
      further studies with larger number of patients are warranted to clarify the true
      diagnostic accuracy and applicability of this approach. 

PMID- 25575986
TI  - Elevated CO2 mitigates drought and temperature-induced oxidative stress
      differently in grasses and legumes.
AB  - Increasing atmospheric CO2 will affect plant growth, including mitigation of
      stress impact. Such effects vary considerably between species-groups. Grasses
      (Lolium perenne, Poa pratensis) and legumes (Medicago lupulina, Lotus
      corniculatus) were subjected to drought, elevated temperature and elevated CO2.
      Drought inhibited plant growth, photosynthesis and stomatal conductance, and
      induced osmolytes and antioxidants in all species. In contrast, oxidative damage
      was more strongly induced in the legumes than in the grasses. Warming generally
      exacerbated drought effects, whereas elevated CO2 reduced stress impact. In the
      grasses, photosynthesis and chlorophyll levels were more protected by CO2 than in
      the legumes. Oxidative stress parameters (lipid peroxidation, H2O2 levels), on
      the other hand, were generally more reduced in the legumes. This is consistent
      with changes in molecular antioxidants, which were reduced by elevated CO2 in the
      grasses, but not in the legumes. Antioxidant enzymes decreased similarly in both
      species-groups. The ascorbate-glutathione cycle was little affected by drought
      and CO2. Overall, elevated CO2 reduced drought effects in grasses and legumes,
      and this mitigation was stronger in the legumes. This is possibly explained by
      stronger reduction in H2O2 generation (photorespiration and NADPH oxidase), and a
      higher availability of molecular antioxidants. The grass/legume-specificity was
      supported by principal component analysis. 

PMID- 25575985
TI  - Obstetric and perinatal outcome in type 1 diabetes patients with diabetic
      nephropathy during 1988-2011.
AB  - AIMS/HYPOTHESIS: Our aim was to analyse possible changes in the glycaemic
      control, BP, markers of renal function, and obstetric and perinatal outcomes of
      parturients with diabetic nephropathy during 1988-2011. METHODS: The most recent
      childbirth of 108 consecutive type 1 diabetes patients with diabetic nephropathy
      and a singleton pregnancy were studied. Two periods, 1988-1999 and 2000-2011,
      were compared. RESULTS: The prepregnancy and the first trimester median HbA1c
      values persisted at high levels (8.2% [66 mmol/mol] vs 8.5% [69 mmol/mol], p =
      0.16 and 8.3% [67 mmol/mol] vs 8.4% [68 mmol/mol], p = 0.67, respectively), but
      decreased by mid-pregnancy (6.7% [50 mmol/mol] vs 6.9% [52 mmol/mol], p = 0.11).
      Antihypertensive medication usage increased before pregnancy (34% vs 65%, p =
      0.002) and in the second and third trimesters of pregnancy (25% vs 47%, p = 0.02,
      and 36% vs 60%, p = 0.01, respectively). BP exceeded 130/80 mmHg in 62% and 61%
      (p = 0.87) of patients in the first trimester, and in 95% and 93% (p = 0.69) in
      the third trimester, respectively. No changes were observed in the markers of
      renal function. Pre-eclampsia (52% vs 42%, p = 0.29) and preterm birth rates
      before 32 and 37 gestational weeks (14% vs 21%, p = 0.33, and 71% vs 77%, p =
      0.49, respectively) remained high. The elective and emergency Caesarean section
      rates were 71% and 45% (p = 0.01) and 29% and 48% (p = 0.05), respectively.
      Neonatal intensive care unit admissions increased from 26% to 49% (p = 0.02).
      CONCLUSIONS/INTERPRETATION: Early pregnancy glycaemic control and hypertension
      management were suboptimal in both time periods. Pre-eclampsia and preterm
      delivery rates remained high in patients with diabetic nephropathy.

PMID- 25575987
TI  - Identification of a xyloglucan-specific endo-(1-4)-beta-D-glucanase inhibitor
      protein from apple (Malus * domestica Borkh.) as a potential defense gene against
      Botryosphaeria dothidea.
AB  - Botryosphaeria dothidea is the causal agent of apple ring rot which is a highly
      destructive apple disease in China. Here, a putative xyloglucan-specific endo-(1
      4)-beta-d-glucanase inhibitor protein from Malus*domestica (designated as
      MdXEGIP1) was found to be involved in defense against B. dothidea infection.
      MdXEGIP1 shares high amino acid sequence identity with other apple XEGIPs, but
      exhibited significantly different responses to B. dothidea infection.
      Quantitative real-time PCR revealed that MdXEGIP1 expression was significantly
      induced in shoot bark of apple plant by B. dothidea and showed different
      expression pattern in resistant and susceptible apple cultivars. In resistant
      cultivar, MdXEGIP1 expression was elevated with larger amplitude than that in
      susceptible cultivar after B. dothidea infection. MdXEGIP1 expression was also
      significantly enhanced by treatment with exogenous methyl jasmonate and salicylic
      acid in apple plantlets. Further investigation revealed that recombinant MdXEGIP1
      has significant inhibitor activity to XEGs from family 12 and 74 of glycoside
      hydrolase. More importantly, recombinant MdXEGIP1 inhibited crude enzyme solution
      of XEG from B. dothidea, suggesting that MdXEGIP1 might protect apple plant from
      B. dothidea infection by inhibiting XEG activity. Taken together, the results
      indicated that MdXEGIP1 is a potential defense gene against B. dothidea in apple.

PMID- 25575988
TI  - Transcriptional control of vitamin C defective 2 and tocopherol cyclase genes by
      light and plastid-derived signals: the partial involvement of GENOMES UNCOUPLED
      1.
AB  - Previous findings have suggested that light and plastid-derived signals are
      involved in the regulation of biosynthetic pathways for l-ascorbic acid (AsA) and
      tocopherols (Toc). Photosynthetic electron transport (PET) activity, plastid gene
      expression (PGE), and the tetrapyrrole metabolism have been identified as signals
      that regulate nuclear gene expression through the GENOMES UNCOUPLED 1 (GUN1)
      protein. Here, we examined the effects of disrupting GUN1 on these pathways. The
      expression of vitamin C defective 2 (VTC2) and tocopherol cyclase (TC) genes,
      which encode key enzymes in the AsA and Toc biosynthetic pathways, respectively,
      was affected by illumination and darkness in parallel with the levels of both
      these antioxidants. However, the GUN1 disruption had no effect on these
      biosynthetic pathways under light-dark conditions. All treatments that inhibited
      PET, PGE, and the tetrapyrrole metabolism interrupted both biosynthetic pathways;
      however, this was partially mitigated by the GUN1 disruption. The expression
      patterns of VTC2 and TC reflected the levels of both antioxidants under most of
      the conditions examined. Our results suggest that the transcriptional control of
      VTC2 and TC by light and plastid-derived signals is important for the regulation
      of the biosynthetic pathways, and that GUN1 is at least partially involved in the
      plastid-derived signals-dependent regulation. 

PMID- 25575989
TI  - Non-climacteric ripening and sorbitol homeostasis in plum fruits.
AB  - During ripening fruits undergo several physiological and biochemical
      modifications that influence quality-related properties, such as texture, color,
      aroma and taste. We studied the differences in ethylene and sugar metabolism
      between two genetically related Japanese plum cultivars with contrasting ripening
      behaviors. 'Santa Rosa' (SR) behaved as a typical climacteric fruit, while the
      bud sport mutant 'Sweet Miriam' (SM) displayed a non-climacteric ripening
      pattern. SM fruit displayed a delayed ripening that lasted 120 days longer than
      that of the climacteric fruit. At the full-ripe stage, both cultivars reached
      similar final size and weight but the non-climacteric fruits were firmer than the
      climacteric fruits. Fully ripe non-climacteric plum fruits, showed an
      accumulation of sorbitol that was 2.5 times higher than that of climacteric
      fruits, and the increase in sorbitol were also paralleled to an increase in
      sucrose catabolism. These changes were highly correlated with decreased activity
      and expression of NAD(+)-dependent sorbitol dehydrogenase and sorbitol oxidase
      and increased sorbitol-6-phosphate dehydrogenase activity, suggesting an enhanced
      sorbitol synthesis in non-climacteric fruits. 

PMID- 25575990
TI  - Ectopic expression of a Catalpa bungei (Bignoniaceae) PISTILLATA homologue
      rescues the petal and stamen identities in Arabidopsis pi-1 mutant.
AB  - PISTILLATA (PI) plays crucial roles in Arabidopsis flower development by
      specifying petal and stamen identities. To investigate the molecular mechanisms
      underlying organ development of woody angiosperm in Catalpa, we isolated and
      identified a PI homologue, referred to as CabuPI (C. bungei PISTILLATA), from two
      genetically cognate C. bungei (Bignoniaceae) bearing single and double flowers.
      Sequence and phylogenetic analyses revealed that the gene is closest related to
      the eudicot PI homologues. Moreover, a highly conserved PI-motif is found in the
      C-terminal regions of CabuPI. Semi-quantitative and quantitative real time PCR
      analyses showed that the expression of CabuPI was restricted to petals and
      stamens. However, CabuPI expression in the petals and stamens persisted
      throughout all floral development stages, but the expression levels were
      different. In 35S::CabuPI transgenic homozygous pi-1 mutant Arabidopsis, the
      second and the third whorl floral organs produced normal petals and a different
      number of stamens, respectively. Furthermore, ectopic expression of the CabuPI in
      transgenic wild-type or heterozygote pi-1 mutant Arabidopsis caused the first
      whorl sepal partially converted into a petal-like structure. These results
      clearly reveal the functional conservation of PI homologues between C. bungei and
      Arabidopsis.

PMID- 25575992
TI  - Improvement of growth, fruit weight and early blight disease protection of tomato
      plants by rhizosphere bacteria is correlated with their beneficial traits and
      induced biosynthesis of antioxidant peroxidase and polyphenol oxidase.
AB  - Five plant growth promoting rhizobacteria (PGPRs) of different genera, newly
      isolated from healthy tomato rhizosphere, were characterized with phosphate
      solubilizing and root colonizing ability. Treatment with these isolates recorded
      a significant increase in seed germination and seedling vigor as well as tomato
      growth and fruit weight which might be partly attributed to the ability of the
      PGPRs to produce IAA and enhance nutrient uptake and chlorophyll content in
      treated plants. More importantly, a strong protection against early blight
      disease was observed in PGPR-pretreated tomato plants infected with Alternaria
      solani which is in accordance with the presence of siderophores, HCN, chitinase
      and glucanase in the isolated PGPRs. Additionally, a significantly enhanced
      accumulation of antioxidant peroxidase (POX) and polyphenol oxidase (PPO) enzymes
      was observed in the PGPR-pretreated plants with or without pathogen infection in
      comparison with water or pathogen control. Notably, the highest increase in POX
      and PPO accumulations was recorded in tomato plants raised from seeds primed with
      TN_Vel-35 strain. A significant upregulation of POX and PPO in tomato plants
      subjected to similar treatment with TN_Vel-35 versus respective control was also
      noticed, further strengthening that the PGPR-induced POX and PPO biosyntheses
      also contribute to PGPR-mediated protection against early blight disease in
      tomato plants. 

PMID- 25575991
TI  - The impact of heat stress targeting on the hormonal and transcriptomic response
      in Arabidopsis.
AB  - Targeting of the heat stress (HS, 40 degrees C) to shoots, roots or whole plants
      substantially affects Arabidopsis physiological responses. Effective stress
      targeting was proved by determination of the expression of HS markers, HsfA2 and
      HSA32, which were quickly stimulated in the targeted organ(s), but remained low
      in non-stressed tissues for at least 2h. When shoots or whole plants were
      subjected to HS, a transient decrease in abscisic acid, accompanied by a small
      increase in active cytokinin levels, was observed in leaves, consistent with
      stimulation of transpiration, the main cooling mechanism in leaves. HS
      application targeted to part of plant resulted in a rapid stimulation of
      expression of components of cytokinin signaling pathway (especially of receptor
      genes) in the non-exposed tissues, which indicated fast inter-organ
      communication. Under all HS treatments, shoot apices responded by transient
      elevation of active cytokinin contents and stimulation of transcription of genes
      involved in photosynthesis and carbohydrate metabolism. Duration of this
      stimulation was negatively correlated with stress strength. The impact of
      targeted HS on the expression of 63 selected genes, including those coding
      regulatory 14-3-3 proteins, was compared. Stimulation of GRF9 (GRF14MU) in
      stressed organs after 2-6h may be associated with plant stress adaptation. 

PMID- 25575993
TI  - Pyramiding taro cystatin and fungal chitinase genes driven by a synthetic
      promoter enhances resistance in tomato to root-knot nematode Meloidogyne
      incognita.
AB  - Meloidogyne incognita, one of the major root-knot nematode (RKN) species in
      agriculture, attacks many plant species, causing severe economic losses. Genetic
      engineering of plants with defense-responsive genes has been demonstrated to
      control RKN. These studies, however, focused on controlling RKN at certain growth
      stages. In the present study, a dual gene overexpression system, utilizing a
      plant cysteine proteinase inhibitor (CeCPI) and a fungal chitinase (PjCHI-1), was
      used to transform tomato (Solanum lycopersicum) in order to provide protection
      from all growth stages of RKN. A synthetic promoter, pMSPOA, containing NOS-like
      and SP8a elements, was employed to drive the expression of introduced genes. Gall
      formation and the proportion of female nematodes in the population, as well as
      effects on the reproduction of RKN, were monitored in both transgenic and control
      plants. RKN eggs collected from transgenic plants displayed reduced chitin
      content and retardation in embryogenesis. The results demonstrated that
      transgenic plants had inhibitory effects on RKN that were superior to plants
      transformed with a single gene. The pyramiding expression system produced
      synergistic effects by the two defense-responsive genes, leading to a detrimental
      effect on all growth stages of RKN. 

PMID- 25575994
TI  - Delayed flowering is associated with lack of photosynthetic acclimation in Pigeon
      pea (Cajanus cajan L.) grown under elevated CO2.
AB  - In the present study, we investigated the likely consequences of future
      atmospheric CO2 concentrations [CO2] on growth, physiology and reproductive
      phenology of Pigeonpea. A short duration Pigeonpea cultivar (ICPL 15011) was
      grown without N fertilizer from emergence to final harvest in CO2 enriched
      atmosphere (open top chambers; 550MUmolmol(-1)) for two seasons. CO2 enrichment
      improved both net photosynthetic rates (Asat) and foliar carbohydrate content by
      36 and 43%, respectively, which further reflected in dry biomass after harvest,
      showing an increment of 29% over the control plants. Greater carboxylation rates
      of Rubisco (Vcmax) and photosynthetic electron transport rates (Jmax) in elevated
      CO2 grown plants measured during different growth periods, clearly demonstrated
      lack of photosynthetic acclimation. Further, chlorophyll a fluorescence
      measurements as indicated by Fv/Fm and DeltaF/Fm' ratios justified enhanced
      photosystem II efficiency. Mass and number of root nodules were significantly
      high in elevated CO2 grown plants showing 58% increase in nodule mass ratio (NMR)
      which directly correlated with Pn. Growth under high CO2 showed significant
      ontogenic changes including delayed flowering. In conclusion, our data
      demonstrate that the lack of photosynthetic acclimation and increased
      carbohydrate-nitrogen reserves modulate the vegetative and reproductive growth
      patterns in Pigeonpea grown under elevated CO2. 

PMID- 25575995
TI  - Deciphering priming-induced improvement of rapeseed (Brassica napus L.)
      germination through an integrated transcriptomic and proteomic approach.
AB  - Rape seeds primed with -1.2 MPa polyethylene glycol 6000 showed improved
      germination performance. To better understand the beneficial effect of
      osmopriming on seed germination, a global expression profiling method was used to
      compare, for the first time, transcriptomic and proteomic data for osmoprimed
      seeds at the crucial phases of priming procedure (soaking, drying), whole priming
      process and subsequent germination. Brassica napus was used here as a model to
      dissect the process of osmopriming into its essential components. A total number
      of 952 genes and 75 proteins were affected during the main phases of priming and
      post-priming germination. Transcription was not coordinately associated with
      translation resulting in a limited correspondence between mRNAs level and protein
      abundance. Soaking, drying and final germination of primed seeds triggered
      distinct specific pathways since only a minority of genes and proteins were
      involved in all phases of osmopriming while a vast majority was involved in only
      one single phase. A particular attention was paid to genes and proteins involved
      in the transcription, translation, reserve mobilization, water uptake, cell cycle
      and oxidative stress processes.

PMID- 25575996
TI  - Light and COP1 regulate level of overexpressed DET1 protein.
AB  - de-etiolated 1 (det1) and constitutive photomorphogenic 1 (cop1) were initially
      identified as constitutively photomorphogenic Arabidopsis mutants, exhibiting
      light-grown phenotypes in the dark. Subsequently, both were shown to be
      components of Damaged DNA Binding protein 1 (DDB1)/CULLIN4-type complexes.
      Arabidopsis has two DDB1 homologues, DDB1A and DDB1B, and DDB1A mutants enhance
      det1 phenotypes. Here we examine ddb1a cop1 double mutants and find that ddb1a
      weakly enhances some cop1 phenotypes but not others, suggesting developmental
      regulation of COP1-DDB1A interaction. DET1 loss of function strongly enhances
      cop1 phenotypes. Here we show that MycDET1 overexpression also enhances cop1
      phenotypes, thus MycDET1 overexpression in cop1 mutants also generates loss of
      function effects. Finally, the effect of the cop1 mutant background on the
      biochemical properties of MycDET1 was examined. MycDET1 levels were found to be
      lower in the dark than in the light and this difference required COP1. In
      summary, both DDB1A loss of function and MycDET1 overexpression enhance cop1
      phenotypes, while cop1 mutants fail to exhibit light regulation of MycDET1
      levels.

PMID- 25575997
TI  - Phosphite cannot be used as a phosphorus source but is non-toxic for microalgae.
AB  - Phosphorous (P) plays a critical role for all living organisms as a structural
      component of RNA, DNA and phospholipids. Microalgae are autotrophs organisms that
      have been reported to only assimilate the fully oxidized phosphate (Pi) as P
      source. However, there are microorganisms capable of utilizing P reduced
      compounds (i.e. phosphite (Phi) and hypophosphite) as a sole P source, such as
      bacteria and cyanobacteria. In this study, we evaluated whether microalgae, such
      as Chlamydomonas reinhardtii, Botryococcus braunii and Ettlia oleoabundans, are
      capable of using Phi as a sole P source. Our studies revealed that these three
      microalgae are unable to use Phi as a sole P source. We also found that when Phi
      is present at concentrations equal or higher than that of Pi, Phi has an
      inhibitory effect on C. reinhardtii growth. However, since C. reinhardtii was
      able to survive for a long period of cultivation in the presence of high
      concentrations of Phi and to recover cell division capacity after transfer to
      media containing Pi, we noticed that Phi is not toxic for this microalga. We
      propose that the inhibitory effect of Phi on C. reinhardtii growth might be
      caused, at least in part, by a competition between the transport of Pi and Phi. 

PMID- 25575998
TI  - Potassium transporter TRH1 subunits assemble regulating root-hair elongation
      autonomously from the cell fate determination pathway.
AB  - Trichoblasts of trh1 plants form root-hair initiation sites that fail to undergo
      tip growth resulting in a tiny root-hair phenotype. TRH1 belongs to Arabidopsis
      KT/KUP/HAK potassium transporter family controlling root-hair growth and
      gravitropism. Double mutant combinations between trh1 and root-hair mutants
      affecting cell fate or root-hair initiation exhibited additive phenotypes,
      suggesting that TRH1 acts independently and developmentally downstream of root
      hair initiation. Bimolecular Fluorescence Complementation (BiFC), upon TRH1
      YFP(C) and TRH1-YFP(N) co-transformation into tobacco epidermal cells, led to
      fluorescence emission indicative of TRH1 subunit homodimerization. Yeast two
      hybrid analysis revealed two types of interactions. The hydrophilic segment
      between the second and the third transmembrane domain extending from residues
      Q105 to T141 is competent for a relatively weak interaction, whereas the region
      at the C-terminal beyond the last transmembrane domain, extending from amino
      acids R565 to A729, strongly self-interacts. These domains likely facilitate the
      co-assembly of TRH1 subunits forming an active K(+) transport system within
      cellular membrane structures. The results support the role of TRH1 acting as a
      convergence point between the developmental root-hair pathway and the
      environmental/hormonal signaling pathway to preserve auxin homeostasis ensuring
      plant adaptation in changing environments.

PMID- 25575999
TI  - Light avoidance reduces ascorbic acid accumulation in the peel of Citrus fruit.
AB  - Citrus fruits are highly consumed worldwide and represent one of the most
      important sources of ascorbic acid (AsA). However, information about the
      molecular mechanisms regulating AsA accumulation in Citrus fruit and the effects
      of environmental factors is scarce. In this study we have investigated the effect
      of fruit shading on AsA content and the expression of AsA biosynthetic, degrading
      and recycling genes in fruits of different Citrus species. Immature-green fruits
      were covered at the end of the cell enlargement phase and AsA concentration in
      the flavedo declined and remained at low levels as compared with light-exposed
      fruits. Fruit shading marginally altered the expression of genes from the l
      galactose pathway and this effect was variable in the four Citrus species.
      However, specific isoforms (GalUR8 or GalUR12) from the l-galacturonic acid
      pathway were significantly repressed paralleling the reduction in AsA
      concentration. No significant effect of shading was detected in transcription of
      genes of the myo-inositol and l-gulose pathways as well as recycling and
      degradation. Collectively, results indicate that light avoidance inhibited
      accumulation of AsA in the flavedo of Citrus fruits and suggest that the l
      galacturonic acid pathway has a relevant contribution to AsA content in this
      tissue. 

PMID- 25576000
TI  - OsARF16, a transcription factor regulating auxin redistribution, is required for
      iron deficiency response in rice (Oryza sativa L.).
AB  - Plant response to iron deficiency is the most important feature for survival in
      Fe-limited soils. Several phytohormones, including auxin, are involved in iron
      uptake and homeostasis. However, the mechanisms behind how auxin participates in
      the iron deficiency response in rice are largely unknown. We found that OsARF16
      was involved in the iron deficiency response and the induction of iron deficiency
      response genes. Most Fe-deficient symptoms could be partially restored in the
      osarf16 mutant, including dwarfism, photosynthesis decline, a reduction in iron
      content and root system architecture (RSA) regulation. OsARF16 expression was
      induced in the roots and shoots by Fe deprivation. Restoration of the phenotype
      could also be mimicked by 1-NOA, an auxin influx inhibitor. Furthermore, the qRT
      PCR data indicated that the induction of Fe-deficiency response genes by iron
      deficiency was more compromised in the osarf16 mutant than in Nipponbare. In
      conclusion, osarf16, an auxin insensitive mutant, was involved in iron deficiency
      response in rice. Our results reveal a new biological function for OsARF16 and
      provide important information on how ARF-medicated auxin signaling affects iron
      signaling and the iron deficiency response. This work may help us to improve
      production or increased Fe nutrition of rice to iron deficiency by regulating
      auxin signaling. 

PMID- 25576001
TI  - Proteomic analysis of changes in the Kandelia candel chloroplast proteins reveals
      pathways associated with salt tolerance.
AB  - The plant chloroplast is one of the most sensitive organelles in response to salt
      stress. Chloroplast proteins extracted from seedling leaves were separated by two
      dimensional gel electrophoresis (2-DE). More than 600 protein spots could be
      distinguished on each gel. Fifty-eight differentially expressed protein spots
      were detected, of which 46 could be identified through matrix-assisted laser
      desorption ionization time-of-flight/time-of-flight mass spectrometry (MALDI
      TOF/TOF-MS). These proteins were found to be involved in multiple aspects of
      chloroplast metabolism pathways such as photosynthesis, ATP synthesis,
      detoxification and antioxidation processes, nitrogen assimilation and fixation,
      protein metabolism, and tetrapyrrole biosynthesis. The results indicated that K.
      candel could withstand up to 500 mM NaCl stress for a measured period of 3 days,
      by maintaining normal or high photosynthetic electron transfer efficiency and an
      only slightly stimulated Calvin cycle. Meanwhile, we found that ROS scavenging,
      nitrogen assimilation, protein degradation and chaperone function in chloroplasts
      were also of importance for salt tolerance of K. candel. The ultrastructural and
      physiological data agree with chloroplast proteome results. These findings allow
      further exploration of our knowledge on salt adaptation in woody halophytes and
      may contribute to the development of more salt-tolerant plants in the future.

PMID- 25576002
TI  - A Japanese plum alpha-l-arabinofuranosidase/beta-D-xylosidase gene is
      developmentally regulated by alternative splicing.
AB  - A full-length cDNA clone named PsARF/XYL was obtained from Prunus salicina
      Lindl., and determined to encode a putative alpha-l-arabinofuranosidase/beta-d
      xylosidase belonging to glycoside hydrolase (GH, EC 3.2.1.-) family 3. Two
      related PsARF/XYL cDNAs were amplified, one from a fully-spliced transcript
      (PsARF/XYLa) and another one from an intron-retained transcript (PsARF/XYLb). The
      protein deduced from PsARF/XYLb is a truncated peptide at C-terminus that
      conserves the active-site amino acid sequence. High levels of PsARF/XYLa and
      PsARF/XYLb transcripts are detectable in several plant tissues. PsARF/XYLb
      transcripts accumulate progressively during the phase of exponential fruit growth
      but they become barely noticeable during on-tree ripening, or after a 6-h
      exposure of preclimacteric full-size plums to ethylene. In contrast, PsARF/XYLa
      is expressed throughout fruit development, and transcript accumulation parallels
      the climacteric rise in ethylene production during ripening. PsARF/XYLa
      expression is strongly induced in preclimacteric full-size plums after a 6-h
      treatment with physiologically active concentrations of ethylene. These findings
      suggest that PsARF/XYL gene is post-transcriptionally regulated by alternative
      splicing during development and that ethylene may be involved in this regulation.
      The isolation of a partial cDNA clone, PsARF1, is also reported. It encodes a
      putative cell-wall alpha-l-arabinofuranosidase, and its transcription is rapidly
      inhibited by ethylene in mature green plums. 

PMID- 25576003
TI  - Overcoming ammonium toxicity.
AB  - Ammonia (ammonium ion under physiological conditions) is one of the key nitrogen
      sources in cellular amino acid biosynthesis. It is continuously produced in
      living organisms by a number of biochemical processes, but its accumulation in
      cells leads to tissue damage. Current knowledge suggests that a few enzymes and
      transporters are responsible for maintaining the delicate balance of ammonium
      fluxes in plant tissues. In this study we analyze the data in the scientific
      literature and the publicly available information on the dozens of biochemical
      reactions in which endogenous ammonium is produced or consumed, the enzymes that
      catalyze them, and the enzyme and transporter mutants listed in plant metabolic
      and genetic databases (Plant Metabolic Network, TAIR, and Genevestigator). Our
      compiled data show a surprisingly high number of little-studied reactions that
      might influence cellular ammonium concentrations. The role of ammonium in
      apoptosis, its relation to oxidative stress, and alterations in ammonium
      metabolism induced by environmental stress need to be explored in order to
      develop methods to manage ammonium toxicity. 

PMID- 25576004
TI  - VvGONST-A and VvGONST-B are Golgi-localised GDP-sugar transporters in grapevine
      (Vitis vinifera L.).
AB  - Plant nucleotide-sugar transporters (NSTs) are responsible for the import of
      nucleotide-sugar substrates into the Golgi lumen, for subsequent use in
      glycosylation reactions. NSTs are specific for either GDP- or UDP-sugars, and
      almost all transporters studied to date have been isolated from Arabidopsis
      thaliana L. In order to determine the conservation of the import mechanism in
      other higher plant species, here we report the identification and
      characterisation of VvGONST-A and VvGONST-B from grapevine (Vitis vinifera L. cv.
      Thompson Seedless), which are the orthologues of the GDP-sugar transporters
      GONST3 and GONST4 in Arabidopsis. Both grapevine NSTs possess the molecular
      features characteristic of GDP-sugar transporters, including a GDP-binding domain
      (GXL/VNK) towards the C-terminal. VvGONST-A and VvGONST-B expression is highest
      at berry setting and decreases throughout berry development and ripening.
      Moreover, we show using green fluorescent protein (GFP) tagged versions and
      brefeldin A treatments, that both are localised in the Golgi apparatus.
      Additionally, in vitro transport assays after expression of both NSTs in tobacco
      leaves indicate that VvGONST-A and VvGONST-B are capable of transporting GDP
      mannose and GDP-glucose, respectively, but not a range of other UDP- and GDP
      sugars. The possible functions of these NSTs in glucomannan synthesis and/or
      glycosylation of sphingolipids are discussed. 

PMID- 25576005
TI  - Overexpression of ShDHN, a dehydrin gene from Solanum habrochaites enhances
      tolerance to multiple abiotic stresses in tomato.
AB  - Dehydrins (DHNs) play important roles in plant adaptation to abiotic stress. In
      this study, a cold-induced SK3-type DHN gene (ShDHN) isolated from wild tomato
      species Solanum habrochaites was characterized for its function in abiotic stress
      tolerance. ShDHN was constitutively expressed in root, leaf, stem, flower and
      fruit. ShDHN was continuously up-regulated during cold stress and showed higher
      expression level in the cold-tolerant S. habrochaites than in the susceptible S.
      lycopersicum. Moreover, ShDHN expression was also regulated by drought, salt,
      osmotic stress, and exogenous signaling molecules. Overexpression of ShDHN in
      cultivated tomato increased tolerance to cold and drought stresses and improved
      seedling growth under salt and osmotic stresses. Compared with the wild-type, the
      transgenic plants accumulated more proline, maintained higher enzymatic
      activities of superoxide dismutase and catalase, and suffered less membrane
      damage under cold and drought stresses. Moreover, the transgenic plants
      accumulated lower levels of H2O2 and O2(-) under cold stress, and had higher
      relative water contents and lower water loss rates under dehydration conditions.
      Furthermore, overexpression of ShDHN in tomato led to the up- or down-regulated
      expression of several genes involved in ROS scavenging and JA signaling pathway,
      including SOD1, GST, POD, LOX, PR1 and PR2. Taken together, these results
      indicate that ShDHN has pleiotropic effects on improving plant adaptation to
      abiotic stresses and that it possesses potential usefulness in genetic
      improvement of stress tolerance in tomato.

PMID- 25576007
TI  - Contracting private hospitals: experiences from Southeast and East Asia.
AB  - In resource-scarce settings governments have increasingly looked at ways of
      engaging the private sector in achieving national health system goals. This study
      is a comparative analysis of institutional contracting for hospital services in
      three southeast and east Asian countries, namely Thailand, the Philippines and
      South Korea. In addition, the case of Singapore, where public hospitals are
      corporatized, is reviewed. Primary data were collected through in-depth
      interviews and analysed under a triangulation approach. Institutional contracting
      is only used in three out of four countries. In these three countries,
      institutional contracting inter alia aims at increasing access to hospital
      services, although the scale of private hospital participation depends on
      contextual factors. Neither strategic provider selection mechanisms nor a
      preferred provider system is part of the institutional contracting models
      reviewed. In Thailand and the Philippines, performance-based rewards or sanctions
      have played a limited role so far and there is relatively little dialogue between
      contract parties, indicating that the contracting tool has not been used to the
      fullest extent possible and suggesting that capacity development especially
      regarding contract and relationship management is needed. Although there is
      virtually no information available about the cost of contracting, the findings of
      this study suggest that the potential of institutional contracting arrangements
      should be explored further to improve health system outcomes and thereby support
      countries in their quest for universal health coverage. 

PMID- 25576006
TI  - An endoplasmic reticulum magnesium transporter is essential for pollen
      development in Arabidopsis.
AB  - Magnesium is one of the essential macro-elements for plant growth and
      development, participated in photosynthesis and various metabolic processes. The
      Mg-transport abilities of the AtMGT (Magnesium Transporter) genes were identified
      in bacteria or yeast mutant system. In our previous studies, both the AtMGT5 and
      AtMGT9 were found essential for pollen development in Arabidopsis. Here we report
      another AtMGT member, AtMGT4, which was localized to the endoplasmic reticulum,
      was essential for pollen development as well. AtMGT4 expressed notably in pollen
      grains from bicellular pollen stage to mature pollen stage. A T-DNA insertional
      mutant of the gene, named mgt4-1, showed pollen abortive phenotype, thus we could
      not get any homozygous mutant from progenies of self-crossed +/mgt4-1 plants.
      Meanwhile, nearly half of pollens in AtMGT4-RNAi transgenic lines were sterile,
      consistent with the phenotype of +/mgt4-1 mutant. Transgenic plants expressing
      AtMGT4 in the mgt4-1 background could recover the pollen fertility to the wild
      type. Together, our findings demonstrated that the disruption of AtMGT4 in
      Arabidopsis could cause a defect of pollen development. The visible pollen
      abortion appeared at bicellular pollen stage in +/mgt4-1.

PMID- 25576008
TI  - Urothelial carcinoma in situ: concerns about daily practice.

PMID- 25576009
TI  - Review of the current management of lower urinary tract injuries by the EAU
      Trauma Guidelines Panel.
AB  - CONTEXT: The most recent European Association of Urology (EAU) guidelines on
      urologic trauma were published in 2014. OBJECTIVE: To present a summary of the
      2014 version of the EAU guidelines on urologic trauma of the lower urinary tract
      with an emphasis on diagnosis and treatment. EVIDENCE ACQUISITION: The EAU Trauma
      Panel reviewed the English-language literature via a Medline search for lower
      urinary tract injury (LUTI) up to November 2013. The focus was on newer
      publications and reviews, although older key references could be included.
      EVIDENCE SYNTHESIS: A full version of the guidelines is available in print (EAU
      Guidelines 2014 edition, ISBN/EAN 978-90-79754-65-6) and online (www.uroweb.org).
      Blunt trauma is the main cause of LUTI. The preferred diagnostic modality for
      bladder and urethral injury is cystography and urethrography, respectively. In
      the treatment of bladder injuries, it is important to distinguish between extra-
      and intraperitoneal ruptures. Treatment of male anterior urethral injuries
      depends on the cause (blunt vs penetrating vs penile-fracture-related injury).
      Blunt posterior urethral injuries can be corrected by immediate/early endoscopic
      realignment. If this is not possible, such injuries are managed by suprapubic
      urinary diversion and deferred (>3 mo) urethroplasty. Treatment of female
      urethral injuries depends on the location of the injury and is usually surgical.
      CONCLUSIONS: Correct treatment of LUTIs is important to minimise long-term
      urinary symptoms and sexual dysfunction. This review performed by the EAU trauma
      panel summarises the current management of LUTIs. PATIENT SUMMARY: Patients with
      trauma to the lower urinary tract benefit from accurate diagnosis and appropriate
      treatment according to the nature and severity of their injury.

PMID- 25576010
TI  - The fibrinolytic system-more than fibrinolysis?
AB  - The fibrinolytic system, known for its ability to regulate the activation of the
      zymogen plasminogen into active plasmin, has been primarily associated with the
      removal of fibrin and blood clots. Tissue-type plasminogen activator, the most
      well-recognized plasminogen activator, was harnessed for therapeutic benefit
      against thromboembolic disorders more than 30 years ago, whereas inhibition of
      this system has been proven effective for certain bleeding disorders. However, in
      recent years, new and unexpected functional roles for this system have been
      identified mostly in relation to the central nervous system that are both
      unrelated and independent of fibrin degradation and clot removal. Hence, it seems
      reasonable to ask whether agents used to modify components or activities of the
      fibrinolytic system have any clinical consequences unrelated to their intended
      use in hemostasis. This review will provide an overview of these new features of
      the fibrinolytic system and will also focus on prospective considerations in the
      use of fibrinolytic and antifibrinolytic agents. 

PMID- 25576011
TI  - Topical application of tranexamic acid in primary total hip arthroplasty: a
      systemic review and meta-analysis.
AB  - OBJECTIVE: A systematic review of randomized controlled trials (RCTs) and non
      RCTs was performed to evaluate efficacy for the reduction of postoperative blood
      loss and transfusion requirements of topical use of tranexamic acid in patients
      undergoing primary total hip arthroplasty. METHOD: Potential articles were
      identified from Medline (1966 - September 2014), Embase (1980 - September 2014),
      Pubmed (1980 - September 2014) and The Cochrane Central Register of Controlled
      Trials. Other internet databases are also searched to find trials according to
      the Cochrane Collaboration guidelines. Moreover, gray literatures are also
      selected from the reference list of the included studies. High quality randomized
      controlled trials (RCTs) and non-RCTs were selected. The software RevMan 5.1 was
      used for the mate-analysis. RESULTS: Four RCTs and four non-RCT meet the
      inclusion criteria. There were significant differences in hemoglobin, total blood
      loss, transfusion requirements and postoperative drainage volume between TXA
      groups and control groups. There were no significant differences in length of
      stay, incidence of wound infection, deep vein thrombosis (DVT) and pulmonary
      embolism (PE) between treatment and control groups. CONCLUSIONS: Present meta
      analysis indicates that the antifibrinolytic agent, also known as tranexamic
      acid, could reduce hemoglobin decline, volume of drainage, total blood loss and
      transfusion requirements after THA, and is not related to adverse reactions or
      complications such as wound infection, DVT and PE.

PMID- 25576013
TI  - Use of a megavoltage electronic portal imaging device to identify prosthetic
      materials.
AB  - To achieve accurate dose calculations in radiation therapy the electron density
      of patient tissues must be known. This information is ordinarily gained from a
      computed tomography (CT) image that has been calibrated to allow relative
      electron density (RED) to be determined from CT number. When high density objects
      such as metallic prostheses are involved, direct use of the CT data can become
      problematic due to the artefacts introduced by high attenuation of the beam. This
      requires manual correction of the density values, however the properties of the
      implanted prosthetic are not always known. A method is introduced where the RED
      of such an object can be determined using the treatment beam of a linear
      accelerator with an electronic portal imaging device. The technique was tested
      using a metallic hip replacement that was placed within a container of water.
      Compared to the theoretical RED of 6.8 for cobalt-chromium alloy, these
      measurements calculated a value of 6.4 +/- 0.7. This would allow the distinction
      of an implant as Co-Cr or steel, which have similar RED, or titanium, which is
      much less dense with an RED of 3.7.

PMID- 25576012
TI  - Conversion of laparoscopic surgery for perforated peptic ulcer: a single-center
      study.
AB  - PURPOSE: A perforated peptic ulcer can be managed laparoscopically in selected
      patients. The purpose of this study was to evaluate whether conversion of
      emergency laparoscopy is inferior to primary median laparotomy in terms of
      postoperative morbidity and mortality. METHODS: We analyzed patients who
      underwent laparoscopic or open surgery for a perforated peptic ulcer at the
      Department of Surgery, University of Schleswig-Holstein, Campus Luebeck between
      January, 1996 and December, 2010. Perforations were graded according to the Boey
      classification, a preoperative risk-scoring system. RESULTS: Conversion to
      laparotomy was necessary in 20 of the 45 patients who underwent laparoscopic
      surgery (CG); therefore, laparoscopic operations were completed in 25 patients
      (LG). The third patient cohort comprised 139 patients who underwent primary
      laparotomy (OG). Overall minor morbidity was significantly lower (p = 0.048) in
      the LG patients than in the OG patients, whereas no significant differences were
      found in major morbidity and mortality, particularly between the OG and CG.
      CONCLUSION: Patients' suitability for laparoscopic management should be decided
      on according to Boey's clinical scoring system. Our findings demonstrated that
      conversion from laparoscopy to laparotomy was not associated with elevated
      postoperative morbidity or mortality versus initial laparotomy. Therefore,
      emergency operations may be commenced laparoscopically in selected patients,
      especially considering the postoperative advantages of this approach.

PMID- 25576014
TI  - Targeted prevention of childhood anxiety: engaging parents in an underserved
      community.
AB  - Selective prevention programs hold the promise of alleviating child anxiety
      symptoms, decreasing the risk for emotional problems across the lifespan. Such
      programs have particular public health import for young children of poor,
      underserved communities. Identifying factors related to parent engagement, and
      methods to improve engagement, are paramount in the effort to develop anxiety
      focused, community prevention programs. This feasibility study investigated the
      effect of an enhanced recruitment strategy to maximize parent engagement, as well
      as factors related to attendance in a single session focused on anxiety
      prevention. Participants were poor, ethnic minority parents of children aged 11
      71 months (n = 256) who completed a survey that assessed anxiety risk according
      to trauma exposure, child anxiety, or parent anxiety, as well as preferences for
      preventive services (phase 1). Those meeting risk criteria (n = 101) were invited
      to a preventive group session (phase 2). Half of parents received enhanced
      recruitment (ER), which included personalized outreach, matching parent
      preferences, and community endorsement. Other parents were invited by mail. Chi
      square analyses indicated that ER was associated with planning to attend (49 vs.
      6% of control). Parents receiving ER were 3.5 times more likely to attend. Higher
      sociodemographic risk was correlated with higher child anxiety symptoms but not
      attendance. Results highlight the need for improved strategies for engaging
      parents in preventive, community-based interventions.

PMID- 25576015
TI  - Community connectedness, challenges, and resilience among gay Latino immigrants.
AB  - To date, relatively little psychological research has focused on the experiences
      of lesbian, gay, bisexual, and transgender (LGBT) Latino/a immigrants to the
      United States. This qualitative study used face-to-face semi-structured
      interviews to explore the unique sources of stress, challenges, as well as
      opportunities and factors related to resilience among 13 gay Latino first- and
      second-generation immigrants. Iterative coding of interview transcripts revealed
      four key themes, each of which is illustrated with verbatim quotes: (1) feelings
      of connectedness to the LGBT community, (2) feelings of connectedness to the
      Latino/a community, (3) intersectional challenges and strategies, and (4) well
      being, strength, and resilience. As suggested by these themes, gay Latino
      immigrants have distinct sources of stress and conflict, many of them associated
      with community memberships, but also draw on unique sources of support and
      adaptive thoughts and behaviors in facing stressors. Implications for studying
      risk and resilience factors among stigmatized populations, including LGBT
      individuals and immigrants, are discussed. 

PMID- 25576016
TI  - Social media as social capital of LGB individuals in Hong Kong: its relations
      with group membership, stigma, and mental well-being.
AB  - Social media are found to facilitate social information exchange among lesbian,
      gay, and bisexual (LGB) individuals who are subjected to social stigma. This
      study tested the protective role of LGB-tailored social media uses and
      gratifications in promoting LGB group membership, which we hypothesized to reduce
      LGB stigma and enhance mental health among LGB individuals in Hong Kong. Based on
      a sample of 233 Chinese LGB individuals in Hong Kong, structural equation
      modeling showed evidence for our hypotheses, chi(df=62)(2)= 88.20, GFI = 0.95,
      CFI = 0.98, NNFI = 0.98, SRMR = 0.07, RMSEA = 0.04. Community surveillance,
      identity expression, and emotional support on social media may promote mental
      health by instilling a sense of group membership and reducing stigma. Social
      media may build camaraderie and bolster resilience among LGB individuals that may
      otherwise be difficult in conservative regions.

PMID- 25576017
TI  - The clock stopped too soon: a tribute to David J.H. Phillips (1952-2014).

PMID- 25576018
TI  - Subgroup analysis of PD tremor with loading: action tremor as a combination of
      classical rest and physiological tremor.
AB  - BACKGROUND: In Parkinson disease, tremor is a challenging symptom to manage,
      partly due to inadequate characterization. The current (classic) model of tremor
      is characterized by a resting tremor with a single strong peak in 3.5-6.5Hz
      range. The presence of action tremor, including postural, isometric, and kinetic
      tremors, has been disputed in the literature but not comprehensively evaluated.
      Analysis of hand tremor in action compared to rest, and possible subgrouping of
      tremor trends, may improve characterization. METHODS: Twenty Parkinson patients
      and 14 controls were recruited. Tremor amplitude was measured across 9
      sequentially loaded tasks, in off and on medication states. Tremor energy was
      separated into 2 frequency bands (B1, 3.5-6.5Hz; B2=physiological tremor, 7.5
      16.5Hz) across all activity levels. Automatic classification was used for
      subgroup analysis. FINDINGS: Automatic classification yielded 3 predominant
      tremor trends (G1, G2, and G3). These were significantly different from each
      other and from controls. G1 demonstrated closest resemblance to classical
      Parkinsonian tremor, with highest tremor energy at rest and with overall
      dominance in B1 for lower loads. G2-G3 did not show tremor energy dominance in
      either band. Medication reduced tremor energy only for G1 in both B1 and B2.
      INTERPRETATION: Subgrouping the loading effect on tremor is a novel and viable
      method of rationalizing (non-classic) action tremor in Parkinson disease. Rest
      and action tremors appear not to be limited to 3.5-6.5Hz and may have
      considerable share of physiological tremor. Finding the contribution of each
      frequency band to total tremor energy and their trends with load may optimize
      therapy options.

PMID- 25576019
TI  - Age-related differences do affect postural kinematics and joint kinetics during
      repetitive lifting.
AB  - BACKGROUND: Age is considered a risk factor for manual handling-related injuries
      and older workers incur higher injury-related costs than younger co-workers. This
      study investigated the differences between the kinematics and kinetics of
      repetitive lifting in two groups of handlers of different ages. METHODS: Fourteen
      younger (mean 24.4 yr) and 14 older (mean 47.2 yr) males participated in the
      study. Participants repetitively lifted a box weighing 13 kg at a frequency of 10
      lifts/min for a maximum of 20 min. Postural kinematics (joint and lumbosacral
      angles and angular velocities) and kinetics (joint moments) were measured
      throughout the lifting task using motion analysis and ground reaction forces.
      Muscle fatigue of the erector spinae was assessed using electromyography.
      FINDINGS: Peak lumbosacral, trunk, hip and knee flexion angles differed
      significantly between age groups over the duration of the task, as did
      lumbosacral and trunk angular velocities. The younger group increased peak lumbar
      flexion by approximately 18% and approached 99% of maximum lumbosacral flexion
      after 20 min, whereas the older group increased lumbar flexion by 4% and
      approached 82% maximum flexion. The younger group had a larger increase in peak
      lumbosacral and trunk angular velocities during extension, which may be related
      to the increased back muscle fatigue observed among the younger group.
      INTERPRETATION: Older participants appeared to control the detrimental effects of
      fatigue associated with repetitive lifting and limit lumbar spine range of
      motion. The higher rates of musculoskeletal injury among older workers may stem
      from a complex interaction of manual handling risk factors.

PMID- 25576020
TI  - Striving for perfection and falling short: The influence of goals on probability
      matching.
AB  - Probability matching in sequential prediction tasks is argued to occur because
      participants implicitly adopt the unrealistic goal of perfect prediction of
      sequences. Biases in the understanding of randomness then lead them to generate
      mixed rather than pure sequences of predictions in attempting to achieve this
      goal. In Study 1, N = 350 participants predicted 100 trials of a binary-outcome
      event. Two factors were manipulated: probability bias (the outcomes were
      equiprobable or distributed with a 75%-25% bias), and goal type-namely, whether
      single-trial predictions or the perfect prediction of four-trial sequences was
      emphasized and rewarded. As we hypothesized, predicting sequences led to more
      probability-matching behavior than did predicting single trials, for both the
      bias and no-bias conditions. In Study 1B, we added a control condition to
      distinguish the effects of the grouped presentation of trials from the effects of
      sequence-level perfect-prediction rewards. The results supported goal type rather
      than presentation format as the cause of the Study 1 differences in matching
      between the sequence and single-trial conditions. In Study 2, all participants (N
      = 300) predicted the outcomes for five-trial sequences, but with different goal
      levels being rewarded: 60%, 80%, or 100% correct predictions. The 100% goal
      resulted in the most probability matching, as hypothesized. Paradoxically, using
      the inferior strategy of probability matching may be triggered by adopting an
      unrealistic perfect-prediction goal.

PMID- 25576021
TI  - Increase in cognitive eating restraint predicts weight loss and change in other
      anthropometric measurements in overweight/obese premenopausal women.
AB  - In modern societies characterized by food abundance, dietary restraint may serve
      as a factor in the successful control of weight or facilitation of weight loss.
      This secondary analysis of data examined whether changes in cognitive eating
      restraint (CER) and disinhibition predicted weight loss in a sample of 60
      overweight/obese premenopausal women [mean +/- SD, age = 35.9 +/- 5.8 y; weight =
      84.4 +/- 13.1 kg; body mass index (BMI) = 31.0 +/- 4.3 kg/m(2)]. Changes in
      weight, BMI, waist circumference, hip circumference, waist-to-hip ratio and body
      fat percentage (BF%) were examined in relation to changes in CER, disinhibition
      and hunger as measured by the Eating Inventory questionnaire at baseline and week
      18 of an 18-week dietary intervention. Multivariate linear regression analysis
      was used to identify predictors of weight loss and changes in other
      anthropometric variables from baseline to study completion. Increase in CER was
      found to be the most robust predictor of reduction in weight (P < 0.0001), BMI (P
      < 0.0001), waist circumference (P < 0.001), hip circumference (P < 0.0001) and
      BF% (P < 0.0001). Effect of increase in CER on change in BMI, hip circumference
      and BF% was moderated by increase in disinhibition (all P < 0.05). Results
      suggest that strategies that target CER and disinhibition should be emphasized in
      programs proposed to treat and prevent obesity. 

PMID- 25576022
TI  - Degree of food processing of household acquisition patterns in a Brazilian urban
      area is related to food buying preferences and perceived food environment.
AB  - OBJECTIVE: This cross-sectional study examined the association between local food
      environment and consumers' acquisition of ultra-processed food. METHODS:
      Households were randomly selected from 36 census tracts in Santos City, Brazil.
      Mothers, of varying economic status, who had children ages 10 or younger (n =
      538) were interviewed concerning: their household food acquisition of 31 groups
      of food and beverages, perceptions of local food environment, food sources
      destinations, means of transportation used, and socioeconomic status. Food
      acquisition patterns were classified based on the degree of industrial food
      processing. Logistic regression models were fitted to assess the association
      between consumer behaviors and acquisition patterns. RESULTS: The large variety
      of fresh produce available in supermarkets was significantly related to lower
      odds of ultra-processed food purchases. After adjusting for sociodemographic
      characteristics, higher odds for minimally-processed food acquisition were
      associated with: frequent use of specialized markets to purchase fruits and
      vegetables (OR 1.89, 95% CI 1.01-2.34), the habit of walking to buy food (OR
      1.58, 95% CI 1.08-2.30), and perceived availability of fresh produce in
      participants' neighborhood (OR 1.58, 95% CI 1.08-2.30). Acquisition of ultra
      processed food was positively associated with the use of taxis as principal means
      of transportation to food sources (OR 2.35, 95% CI 1.08-5.13), and negatively
      associated with perceived availability of a variety of fruits and vegetables in
      the neighborhood (OR 0.57, 95% CI 0.37-0.88). CONCLUSION: The results suggest
      that interventions aiming to promote acquisition of less processed food in
      settings similar to Santos, may be most effective if they focus on increasing the
      number of specialized fresh food markets in local neighborhood areas, improve
      residents' awareness of these markets' availability, and provide appropriate
      transportation.

PMID- 25576023
TI  - Synergistic effects of social support and self-efficacy on dietary motivation
      predicting fruit and vegetable intake.
AB  - BACKGROUND: Self-efficacy and social support are considered relevant predictors
      of fruit and vegetable intake. This study examines whether the effect of self
      efficacy on fruit and vegetable intake is mediated by intention and whether this
      motivational process is moderated by received dietary social support. METHODS: A
      longitudinal study with two measurement points in time, four weeks apart, on
      fruit and vegetable intake was carried out with 473 students aged 19 years on
      average (52% women). In a conditional process analysis, dietary intention was
      specified as a mediator between self-efficacy and fruit and vegetable intake,
      whereas received dietary support was specified as a moderator of the self
      efficacy-intention association, controlling for baseline fruit and vegetable
      intake. RESULTS: Self-efficacy was positively associated with fruit and vegetable
      intake four weeks later, and intention mediated this process. Moreover, an
      interaction between received dietary support and self-efficacy on intention
      emerged. CONCLUSIONS: The effect of self-efficacy on fruit and vegetable intake
      was fully mediated by intention. Moreover, received support exhibited a
      moderating role within the motivational process: high dietary support appeared to
      accentuate the positive relationship between self-efficacy and dietary intention.

PMID- 25576024
TI  - Human-associated fluoroquinolone-resistant Escherichia coli clonal lineages,
      including ST354, isolated from canine feces and extraintestinal infections in
      Australia.
AB  - Phylogenetic group D extraintestinal pathogenic Escherichia coli (ExPEC),
      including O15:K52:H1 and clonal group A, have spread globally and become
      fluoroquinolone-resistant. Here we investigated the role of canine feces as a
      reservoir of these (and other) human-associated ExPEC and their potential as
      canine pathogens. We characterized and compared fluoroquinolone-resistant E. coli
      isolates originally identified as phylogenetic group D from either the feces of
      hospitalized dogs (n = 67; 14 dogs) or extraintestinal infections (n = 53; 33
      dogs). Isolates underwent phylogenetic grouping, random amplified polymorphic DNA
      (RAPD) analysis, virulence genotyping, resistance genotyping, human-associated
      ExPEC O-typing, and multi-locus sequence typing. Five of seven human-associated
      sequence types (STs) exhibited ExPEC-associated O-types, and appeared in separate
      RAPD clusters. The largest subgroup (16 fecal, 26 clinical isolates) were ST354
      (phylogroup F) isolates. ST420 (phylogroup B2); O1-ST38, O15:K52:H1-ST393, and
      O15:K1-ST130 (phylogroup D); and O7-ST457, and O1-ST648 (phylogroup F) were also
      identified. Three ST-specific RAPD sub-clusters (ST354, ST393, and ST457)
      contained closely related isolates from both fecal or clinical sources. Genes
      encoding CTX-M and AmpC beta-lactamases were identified in isolates from five
      STs. Major human-associated fluoroquinolone-resistant +/- extended-spectrum
      cephalosporin-resistant ExPEC of public health importance may be carried in dog
      feces and cause extraintestinal infections in some dogs.

PMID- 25576025
TI  - The adhesive protein invasin of Yersinia pseudotuberculosis induces neutrophil
      extracellular traps via beta1 integrins.
AB  - Yersinia pseudotuberculosis adhesive protein invasin is crucial for the bacteria
      to cross the intestine epithelium by binding to beta1 integrins on M-cells and
      gaining access to the underlying tissues. After the crossing invasin can bind to
      beta1 integrins on other cell surfaces, however effector proteins delivered by
      the type III secretion system Y. pseudotuberculosis efficiently inhibit potential
      immune responses induced by this interaction. Here, we use mutant Y.
      pseudotuberculosis strains lacking the type III secretion system and additionally
      invasin-expressing Escherichia coli to analyze neutrophil responses towards
      invasin. Our data reveals that invasin induces production of reactive oxygen
      species and release of chromatin into the extracellular milieu, which we
      confirmed to be neutrophil extracellular traps by immunofluorescence microscopy.
      This was mediated through beta1 integrins and was dependent on both the
      production of reactive oxygen species and signaling through phosphoinositide 3
      kinase. We therefore have gained insight into a potential role of integrins in
      inflammation and infection clearance that has not previously been described,
      suggesting that targeting of beta1 integrins could be utilized as an adjunctive
      therapy against yersiniosis. 

PMID- 25576026
TI  - Group B Streptococcus pili mediate adherence to salivary glycoproteins.
AB  - Group B Streptococcus (GBS) is a leading cause of neonatal sepsis, pneumonia and
      meningitis, and is responsible for a rising number of severe invasive infections
      in adults. For all disease manifestations, colonisation is a critical first step.
      GBS has frequently been isolated from the oropharynx of neonates and adults.
      However, little is understood about the mechanisms of GBS colonisation at this
      site. In this study it is shown that three GBS strains (COH1, NEM316, 515) have
      capacity to adhere to human salivary pellicle. Heterologous expression of GBS
      pilus island (PI) genes in Lactococcus lactis to form surface-expressed pili
      demonstrated that GBS PI-2a and PI-1 pili bound glycoprotein-340 (gp340), a
      component of salivary pellicle. By contrast, PI-2b pili did not interact with
      gp340. The variation was attributable to differences in capacities for backbone
      and ancillary protein subunits of each pilus to bind gp340. Furthermore, while
      GBS strains were aggregated by fluid-phase gp340, this mechanism was not mediated
      by pili, which displayed specificity for immobilised gp340. Thus pili may enable
      GBS to colonise the soft and hard tissues of the oropharynx, while evading an
      innate mucosal defence, with implications for risk of progression to severe
      diseases such as meningitis and sepsis. 

PMID- 25576027
TI  - The requirement of histone modification by PRDM12 and Kdm4a for the development
      of pre-placodal ectoderm and neural crest in Xenopus.
AB  - In vertebrates, pre-placodal ectoderm and neural crest development requires
      morphogen gradients and several transcriptional factors, while the involvement of
      histone modification remains unclear. Here, we report that histone-modifying
      factors play crucial roles in the development of pre-placodal ectoderm and neural
      crest in Xenopus. During the early neurula stage, PRDM12 was expressed in the
      lateral pre-placodal ectoderm and repressed the expression of neural crest
      specifier genes via methylation of histone H3K9. ChIP-qPCR analyses indicated
      that PRDM12 promoted the occupancy of the trimethylated histone H3K9 (H3K9me3) on
      the Foxd3, Slug, and Sox8 promoters. Injection of the PRDM12 MO inhibited the
      expression of presumptive trigeminal placode markers and decreased the occupancy
      of H3K9me3 on the Foxd3 promoter. Histone demethylase Kdm4a also inhibited the
      expression of presumptive trigeminal placode markers in a similar manner to
      PRDM12 MO and could compensate for the effects of PRDM12. ChIP-qPCR analyses
      revealed that promotion of the occupancy of H3K9me3 on the Foxd3, Slug, and Sox8
      promoters was inhibited by Kdm4a overexpression. Taken together, these data
      indicate that histone modification was essential for pre-placodal ectoderm and
      neural crest development. 

PMID- 25576028
TI  - Tug of war--the influence of opposing physical forces on epithelial cell
      morphology.
AB  - The shape of a single animal cell is determined both by its internal cytoskeleton
      and through physical interactions with its environment. In a tissue context, this
      extracellular environment is made up largely of other cells and the extracellular
      matrix. As a result, the shape of cells residing within an epithelium will be
      determined both by forces actively generated within the cells themselves and by
      their deformation in response to forces generated elsewhere in the tissue as they
      propagate through cell-cell junctions. Together these complex patterns of forces
      combine to drive epithelial tissue morphogenesis during both development and
      homeostasis. Here we review the role of both active and passive cell shape
      changes and mechanical feedback control in tissue morphogenesis in different
      systems. 

PMID- 25576029
TI  - Epithelial and neural cadherin expression in the mammalian reproductive tract and
      gametes and their participation in fertilization-related events.
AB  - Mammalian fertilization involves a series of well-orchestrated cell-cell
      interaction steps between gametes, as well as among spermatozoa and somatic cells
      of both the male and female reproductive tracts. Cadherins are Ca(2+)-dependent
      glycoproteins that have been involved in cellular adhesion and signaling in
      somatic cells. Taking into account that Ca(2+) ions are required during
      fertilization, the involvement of these proteins in adhesion events during this
      process can be anticipated. This report presents an overview on two members of
      classical cadherins, Epithelial (E-) and Neural (N-) cadherin in reproductive
      biology. Its provides evidence of studies done by several research groups about
      the expression of E- and N-cadherin during spermatogenesis, oogenesis and
      folliculogenesis, and their involvement in gamete transport in the reproductive
      tracts. Moreover, it describes current knowledge of E- and N-cadherin presence in
      cells of the cumulus-oocyte complex and spermatozoa from several mammalian
      species, and shows gathered evidence on their participation in different steps of
      the fertilization process. A brief summary on general information of both
      proteins is also presented. 

PMID- 25576030
TI  - Characteristics of spermatozoa and reproductive organs in relation to age and
      body weight in Swedish moose (Alces alces).
AB  - Knowledge of the reproductive biology of game species is vital for sustainable
      management. In moose (Alces alces), research in reproductive characteristics has
      focused on the female, whereas there are few studies in male moose. The aim of
      the present study was to investigate sperm morphology and chromatin integrity
      (SCSA), and their relationships with testicular and epididymal features, as well
      as temporal aspects with respect to the hunting season. In total, 143 male moose
      aged 1.5-11.5 years were sampled from 2008 to 2011. The proportion of normal
      spermatozoa (PNS) ranged from 1.5% to 82.0%, with a mean of 51%, and the %DFI
      (DNA fragmentation index) ranged from 2.5% to 36.7% (mean 9.5). PNS decreased
      temporally, and was positively associated with carcass and testes weight. Body
      weight and testes weight had positive effect on PNS regardless of age. No effect
      of any explanatory variables was observed on the DFI. The testis/body weight
      ratio of moose (0.033%) is among the lowest reported among mammals, indicating a
      less polygynous mating system than in roe deer and red deer. For reproduction
      success in moose, a high body weight in males is favorable, as is a balanced sex
      ratio. Thus, males should not be harvested prior to the time when the majority of
      females have passed their first oestrus of the season. 

PMID- 25576031
TI  - India plans to track use of toilets in rural areas to encourage their use.

PMID- 25576032
TI  - Self emulsifying drug delivery system for enhanced solubility and dissolution of
      glipizide.
AB  - The aim of this study was to develop self emulsifying drug delivery systems
      (SEDDS) of glipizide and to convert it into solid SEDDS (S-SEDDS) using
      Syloid((r)) 244 FP as adsorbent. Solubility study, ternary phase diagram,
      robustness to dilution, thermodynamic stability study and globule size analysis
      were adopted to optimize liquid SEDDS. S-SEDDS were evaluated for various studies
      including in vivo study. The optimized liquid SEDDS formulation consisted of
      phosphatidylcholine, Tween 80 and Transcutol P as oil, surfactant and cosolvent.
      In vivo study demonstrated that blood glucose levels were efficiently controlled
      with S-SEDDS compared with pure drug. The results of this study suggest the
      potential use of developed S-SEDDS formulation for the delivery of poorly water
      soluble drug glipizide. 

PMID- 25576033
TI  - The sum is more than the parts: crystal and solution data reveal that the
      PIDDosome core complex is a dynamic assembly.

PMID- 25576034
TI  - Stress cardiomyopathy: Thinking outside the octopus pot.

PMID- 25576035
TI  - Mechanical support of patients with heart failure: What are the future hurdles?

PMID- 25576036
TI  - The broken heart syndrome: Takotsubo cardiomyopathy.
AB  - First described in 1990, Takotsubo cardiomyopathy consists of a transient
      systolic dysfunction of localized segments of the left ventricle. Commonly
      occurring in postmenopausal women, Takotsubo is often associated with intense
      physical and/or emotional stress. It is traditionally identified by distinctive
      wall motion patterns on transthoracic echocardiogram and left ventriculography.
      Further understanding of the disease mechanisms and recognition of at-risk
      populations has potentially tremendous therapeutic benefit. 

PMID- 25576037
TI  - EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using
      polymeric nanocomplex.
AB  - BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is overexpressed in solid
      tumors and regarded as a putative cancer stem cell marker. Here, we report that
      employing EpCAM aptamer (EpApt) and EpCAM siRNA (SiEp) dual approach, for the
      targeted delivery of siRNA to EpCAM positive cancer cells, efficiently inhibits
      cancer cell proliferation. RESULTS: Targeted delivery of siRNA using
      polyethyleneimine is one of the efficient methods for gene delivery, and thus, we
      developed a novel aptamer-PEI-siRNA nanocomplex for EpCAM targeting. PEI
      nanocomplex synthesized with EpCAM aptamer (EpApt) and EpCAM siRNA (SiEp) showed
      198 nm diameter sized particles by dynamic light scattering, spherical shaped
      particles, of 151 +/- 11 nm size by TEM. The surface charge of the nanoparticles
      was -30.0 mV using zeta potential measurements. Gel retardation assay confirmed
      the PEI-EpApt-SiEp nanoparticles formation. The difference in size observed by
      DLS and TEM could be due to coating of aptamer and siRNA on PEI nanocore. Flow
      cytometry analysis revealed that PEI-EpApt-SiEp has superior binding to cancer
      cells compared to EpApt or scramble aptamer (ScrApt) or PEI-ScrApt-SiEp. PEI
      EpApt-SiEp downregulated EpCAM and inhibited selectively the cell proliferation
      of MCF-7 and WERI-Rb1 cells. CONCLUSIONS: The PEI nanocomplex fabricated with
      EpApt and siEp was able to target EpCAM tumor cells, deliver the siRNA and
      silence the target gene. This nanocomplex exhibited decreased cell proliferation
      than the scrambled aptamer loaded nanocomplex in the EpCAM expressing cancer
      cells and may have potential for EpCAM targeting in vivo.

PMID- 25576038
TI  - Synthesis of variants of Marfey's reagent having d-amino acids as chiral
      auxiliaries and liquid-chromatographic enantioseparation of (RS)-Mexiletine in
      spiked plasma: assessment and comparison with L-amino acid analogs.
AB  - Five d-amino acids have been used for the first time to synthesize chiral
      derivatizing reagents (as variants of Marfey's reagent) by nucleophilic
      displacement of one of the fluorine atoms in 1,5-difluoro-2,4-dinitrobenzene as
      against the literature reports on application of only l-amino acids or their
      amides as chiral auxiliaries in dinitrobenzene (DNB) moiety. Five other DNB based
      reagents were also prepared by nucleophilic substitution of fluorine atom with
      the set of the same amino acids in l-configuration, as chiral auxiliaries. These
      reagents were characterized and used for synthesis of diastereomers of (RS)
      Mexiletine spiked in human plasma. Diastereomers were synthesized employing
      microwave irradiation and were separated on reversed-phase C18 column.
      Performance of the two types of chiral derivatizing reagents was compared. The
      reagents containing d-amino acids provided enhanced separation of diastereomers
      than those containing l-amino acids. The best resolution was obtained using
      mobile phase consisting of acetonitrile and 0.1% trifluoroacetic acid in gradient
      mode. The detection was carried out at 340nm. The method so developed was
      validated for linearity, accuracy and precision. The limit of quantitation was
      found to be approximately 25.2ngmL(-1) in human plasma. 

PMID- 25576039
TI  - Simplified in vitro refolding and purification of recombinant human granulocyte
      colony stimulating factor using protein folding cation exchange chromatography.
AB  - Protein folding-strong cation exchange chromatography (PF-SCX) has been employed
      for efficient refolding with simultaneous purification of recombinant human
      granulocyte colony stimulating factor (rhG-CSF). To acquire a soluble form of
      renatured and purified rhG-CSF, various chromatographic conditions, including the
      mobile phase composition and pH was evaluated. Additionally, the effects of
      additives such as urea, amino acids, polyols, sugars, oxidizing agents and their
      amalgamations were also investigated. Under the optimal conditions, rhG-CSF was
      efficaciously solubilized, refolded and simultaneously purified by SCX in a
      single step. The experimental results using ribose (2.0M) and arginine (0.6M)
      combination were found to be satisfactory with mass yield, purity and specific
      activity of 71%, >=99% and 2.6*10(8)IU/mg respectively. Through this
      investigation, we concluded that the SCX refolding method was more efficient than
      conventional methods which has immense potential for the large-scale production
      of purified rhG-CSF. 

PMID- 25576040
TI  - Lewis acid/base character and crystallisation properties of poly(butylene
      terephthalate).
AB  - Two grades of poly(butylene terephthalate) were analysed by means of inverse gas
      chromatography (IGC) and the results correlated with the respective
      crystallisation properties. The following parameters were determined by IGC: the
      dispersive component of the surface tension, the enthalpy and the entropy of
      adsorption of selected polar and apolar probes, and the Lewis acidity and
      basicity constants, Ka and Kb respectively. The interpretation of the values
      determined for Ka and Kb is in agreement with the FTIR spectra relating to the
      carboxyl end-group and the hydroxyl end-group concentrations in these polymers.
      The differences in the molecular weight values and in the end-group type and
      concentration, between the two grades of PBT, do not cause differences in the
      crystallisation activation energy. This observation suggests that there is a
      leading contribution of the Lewis basic sites to the crystallisation activation
      energy of the grades of PBT that were analysed. However, the lower value of Ka
      and the greater molar mass of one of the PBT grades lead to a corresponding lower
      crystallisation degree. 

PMID- 25576041
TI  - Prion protein-coated magnetic beads: synthesis, characterization and development
      of a new ligands screening method.
AB  - Prion diseases are characterized by protein aggregation and neurodegeneration.
      Conversion of the native prion protein (PrP(C)) into the abnormal scrapie PrP
      isoform (PrP(Sc)), which undergoes aggregation and can eventually form amyloid
      fibrils, is a critical step leading to the characteristic path morphological
      hallmark of these diseases. However, the mechanism of conversion remains unclear.
      It is known that ligands can act as cofactors or inhibitors in the conversion
      mechanism of PrP(C) into PrP(Sc). Within this context, herein, we describe the
      immobilization of PrP(C) onto the surface of magnetic beads and the morphological
      characterization of PrP(C)-coated beads by fluorescence confocal microscopy.
      PrP(C)-coated magnetic beads were used to identify ligands from a mixture of
      compounds, which were monitored by UHPLC-ESI-MS/MS. This affinity-based method
      allowed the isolation of the anti-prion compound quinacrine, an inhibitor of PrP
      aggregation. The results indicate that this approach can be applied to not only
      "fish" for anti-prion compounds from complex matrixes, but also to screening for
      and identify possible cellular cofactors involved in the deflagration of prion
      diseases. 

PMID- 25576042
TI  - Determination of trichloroanisole and trichlorophenol in wineries' ambient air by
      passive sampling and thermal desorption-gas chromatography coupled to tandem mass
      spectrometry.
AB  - The present paper describes the calibration of selected passive samplers used in
      the quantitation of trichlorophenol and trichloroanisole in wineries' ambient
      air, by calculating the corresponding sampling rates. The method is based on
      passive sampling with sorbent tubes and involves thermal desorption-gas
      chromatography-triple quadrupole mass spectrometry analysis. Three commercially
      available sorbents were tested using sampling cartridges with a radial design
      instead of axial ones. The best results were found for Tenax TATM. Sampling rates
      (R-values) for the selected sorbents were determined. Passive sampling was also
      used for accurately determining the amount of compounds present in the air.
      Adequate correlation coefficients between the mass of the target analytes and
      exposure time were obtained. The proposed validated method is a useful tool for
      the early detection of trichloroanisole and its precursor trichlorophenol in
      wineries' ambient air while avoiding contamination of wine or winery facilities. 

PMID- 25576043
TI  - Matrix precipitation: a general strategy to eliminate matrix interference for
      pharmaceutical toxic impurities analysis.
AB  - Matrix interference, which can lead to false positive/negative results,
      contamination of injector or separation column, incompatibility between sample
      solution and the selected analytical instrument, and response inhibition or even
      quenching, is commonly suffered for the analysis of trace level toxic impurities
      in drug substance. In this study, a simple matrix precipitation strategy is
      proposed to eliminate or minimize the above stated matrix interference problems.
      Generally, a sample of active pharmaceutical ingredients (APIs) is dissolved in
      an appropriate solvent to achieve the desired high concentration and then an anti
      solvent is added to precipitate the matrix substance. As a result, the target
      analyte is extracted into the mixed solution with very less residual of APIs.
      This strategy has the characteristics of simple manipulation, high recovery and
      excellent anti-interference capability. It was found that the precipitation ratio
      (R, representing the ability to remove matrix substance) and the proportion of
      solvent (the one used to dissolve APIs) in final solution (P, affecting R and
      also affecting the method sensitivity) are two important factors of the
      precipitation process. The correlation between R and P was investigated by
      performing precipitation with various APIs in different solvent/anti-solvent
      systems. After a detailed mathematical reasoning process, P=20% was proved to be
      an effective and robust condition to perform the precipitation strategy. The
      precipitation method with P=20% can be used as a general strategy for toxic
      impurity analysis in APIs. Finally, several typical examples are described in
      this article, where the challenging matrix interference issues have been resolved
      successfully. 

PMID- 25576044
TI  - Screening of oil sources by using comprehensive two-dimensional gas
      chromatography/time-of-flight mass spectrometry and multivariate statistical
      analysis.
AB  - Using comprehensive two-dimensional gas chromatography coupled to time-of-flight
      mass spectrometry (GC*GC/TOFMS), volatile and semi-volatile organic compounds in
      crude oil samples from different reservoirs or regions were analyzed for the
      development of a molecular fingerprint database. Based on the GC*GC/TOFMS
      fingerprints of crude oils, principal component analysis (PCA) and cluster
      analysis were used to distinguish the oil sources and find biomarkers. As a
      supervised technique, the geological characteristics of crude oils, including
      thermal maturity, sedimentary environment etc., are assigned to the principal
      components. The results show that tri-aromatic steroid (TAS) series are the
      suitable marker compounds in crude oils for the oil screening, and the relative
      abundances of individual TAS compounds have excellent correlation with oil
      sources. In order to correct the effects of some other external factors except
      oil sources, the variables were defined as the content ratio of some target
      compounds and 13 parameters were proposed for the screening of oil sources. With
      the developed model, the crude oils were easily discriminated, and the result is
      in good agreement with the practical geological setting. 

PMID- 25576047
TI  - The Lone Ranger's mask sign.

PMID- 25576045
TI  - Prognostic value of an immediate lateral standing X-ray with a TLSO in patients
      with a thoracolumbar burst fracture.
AB  - The final collapse of a "stable" thoracolumbar burst fracture is difficult to
      predict. This collapse was prospectively studied radiologically in patients with
      T12 or L1 burst fractures who, after evaluating the admission x-rays and the CT
      scan with the patients themselves, opted for a rigid thoracolumbar brace with
      support in the sternal manubrium (TLSO). On the other hand, patients with rigid
      braces sometimes have low back pain on follow-up (due to overload of the L5-S1
      joints). HYPOTHESIS: the standing lateral x-ray with only a TLSO for support
      (intrinsic mechanical stability) provides information on the final collapse and
      could also provide information on the low back pain. The study included 50
      patients (20 males and 30 females, age: 63+14 years) admitted during 2011 and
      2012, with 2 losses to follow-up. VARIABLES: Farcy index and local kyphosis (Cobb
      at 3 vertebrae). X-Rays: admission, with TLSO (immediate: Rx0), and at 3 and 6
      months. They were compared with the final clinical and radiological results. It
      was decided to surgically intervene in 4 patients after Rx0. There were no
      painful sequelae at the fracture level, and 16/44 (31%) had low back pain. Using
      linear regression mathematical models, the increase in the Farcy index (Rx0-Rx
      admission) was associated with the appearance of low back pain and with local
      kyphosis (Rx0-Rx admission), and with the final kyphosis. It is advisable to
      perform a lateral standing X-ray after TLSO for information on the final collapse
      of the fracture and the appearance of accompanying low back pain.

PMID- 25576046
TI  - Radioiodine remnant ablation in low-risk differentiated thyroid cancer: the "con"
      point of view.
AB  - A growing body of evidence is challenging the indiscriminate use of postoperative
      radioiodine for remnant ablation (RRA) in low-risk (LR) differentiated thyroid
      cancer patients. We critically reviewed the current evidence on which the
      rationale for RRA is based for LR patients and analyzed the new evidence-based
      recommendations for LR patients from the draft of the 2015 American Thyroid
      Association (ATA) guidelines. Cost-effective tools for staging and follow-up,
      such as neck ultrasonography and serial thyroglobulin testing, are useful for
      monitoring non-RRA-treated patients. Recurrence rates are very low in non-RRA
      treated LR patient cohorts. Most RRA side effects are mild and transient, but can
      impair a patient's quality of life. RRA is appropriately not routinely
      recommended in LR patients according to the draft 2015 ATA guidelines and should
      be reserved for higher-risk patients. 

PMID- 25576048
TI  - 18F-FDG PET/CT as a potential predictor of survival in patient with oesophageal
      cancer: a preliminary result.
AB  - AIMS: A study was undertaken to investigate the value of pretreatment PET-CT in
      predicting survival in patients with oesophageal cancer (OC). METHODS: Between
      June 2010 and December 2011, 18 consecutive OC patients median (61.00 +/- 12.07
      years) with median survival of 7.5 month had a pretreatment PET-CT scan. Staging
      of the disease was made in accordance to the American Joint Committee on Cancer
      staging system (7th edition) and grouped as stage I-IIA and stage IIB-IV. Maximum
      standardized uptake value (SUVmax), size of a primary tumour and the presence of
      fluorodeoxyglucose (FDG)-avid lymph nodes were evaluated for all patients.
      Survival was analysed using the Kaplan-Meier product limit method and Cox
      proportional hazards regression model. RESULTS: PET-CT stages I-IIA and IIB-IV
      had a 1-year survival of 50% and 25%, respectively. Patient with size of primary
      tumour (<4.5 cm) had significantly (p < 0.036) better survival than those with
      large size (>4.5 cm). Multivariate Cox regression analysis showed that SUVmax of
      >5.5 in the primary tumour [hazard ratio (HR) 23.017; 95% confidence interval, p
      = 0.038] and the presence of FDG-avid lymph node (HR 1.248; p = 0.028) were
      strongly predictive of poor overall survival on multivariate analysis.
      CONCLUSION: Pretreatment 18F-FDG PET-CT SUVmax of a primary tumour and the
      presence of FDG-avid lymph nodes independently predict survival in patients with
      oesophageal carcinoma which may potentially be used as surrogate markers for
      prognostic and therapeutic purposes.

PMID- 25576049
TI  - Incidental findings detected on emergency abdominal CT scans: a 1-year review.
AB  - INTRODUCTION: In recent years, there has been a substantial rise in the use of
      computed tomography (CT) in the emergency medicine setting. Accordingly, with
      increased CT usage there has been an upsurge in incidental pathology detection.
      METHODS: A retrospective review of all emergency CT abdominal scans performed at
      a university teaching hospital was examined. The frequency of incidental
      findings, their clinical significance and workload effect for the radiology
      department was assessed. RESULTS: 1155 patients had an emergency abdominal CT
      scan of which 700 had incidental findings detected. Of the incidental findings,
      143 were deemed indeterminate requiring urgent investigations. Twenty-four occult
      neoplasms were confirmed subsequently. Additionally, 259 patients were
      recommended for additional diagnostics. The cumulative effect of the initial
      emergency abdominal CT was 15,015 relative value units (RVU). Subsequent imaging
      of incidental findings resulted in another 1674 RVU workload for radiology.
      CONCLUSION: Incidental findings cause considerable debate and concern over which
      patients require significant follow-up, investigations, and/or surveillance. This
      exerts significant pressures on sub-specialties for their expert input, with
      increased workload and implications on healthcare service provision.

PMID- 25576050
TI  - The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism
      in skeletal muscle.
AB  - Insulin and exercise stimulate glucose uptake into skeletal muscle via different
      pathways. Both stimuli converge on the translocation of the glucose transporter
      GLUT4 from intracellular vesicles to the cell surface. Two Rab guanosine
      triphosphatases-activating proteins (GAPs) have been implicated in this process:
      AS160 for insulin stimulation and its homolog, TBC1D1, are suggested to regulate
      exercise-mediated glucose uptake into muscle. TBC1D1 has also been implicated in
      obesity in humans and mice. We investigated the role of TBC1D1 in glucose
      metabolism by generating TBC1D1(-/-) mice and analyzing body weight, insulin
      action, and exercise. TBC1D1(-/-) mice showed normal glucose and insulin
      tolerance, with no difference in body weight compared with wild-type littermates.
      GLUT4 protein levels were reduced by ~40% in white TBC1D1(-/-) muscle, and
      TBC1D1(-/-) mice showed impaired exercise endurance together with impaired
      exercise-mediated 2-deoxyglucose uptake into white but not red muscles. These
      findings indicate that the RabGAP TBC1D1 plays a key role in regulating GLUT4
      protein levels and in exercise-mediated glucose uptake in nonoxidative muscle
      fibers.

PMID- 25576051
TI  - miR-30 promotes thermogenesis and the development of beige fat by targeting
      RIP140.
AB  - Members of the microRNA (miR)-30 family have been reported to promote
      adipogenesis and inhibit osteogenesis, yet their role in the regulation of
      thermogenesis remains unknown. In this study, we show that miR-30b/c
      concentrations are greatly increased during adipocyte differentiation and are
      stimulated by cold exposure or the beta-adrenergic receptor activator.
      Overexpression and knockdown of miR-30b and -30c induced and suppressed,
      respectively, the expression of thermogenic genes such as UCP1 and Cidea in brown
      adipocytes. Forced expression of miR-30b/c also significantly increased
      thermogenic gene expression and mitochondrial respiration in primary adipocytes
      derived from subcutaneous white adipose tissue, demonstrating a promoting effect
      of miRNAs on the development of beige fat. In addition, knockdown of miR-30b/c
      repressed UCP1 expression in brown adipose tissue in vivo. miR-30b/c targets the
      3'-untranslated region of the receptor-interacting protein 140 (RIP140), and
      overexpression of miR-30b/c significantly reduced RIP140 expression. Consistent
      with RIP140 as a target of miR-30b/c in regulating thermogenic gene expression,
      overexpression of RIP140 greatly suppressed the promoting effect of miR-30b/c on
      the expression of UCP1 and Cidea in brown adipocytes. Taken together, the data
      from our study identify miR-30b/c as a key regulator of thermogenesis and uncover
      a new mechanism underlying the regulation of brown adipose tissue function and
      the development of beige fat.

PMID- 25576052
TI  - Blunted brain energy consumption relates to insula atrophy and impaired glucose
      tolerance in obesity.
AB  - Brain energy consumption induced by electrical stimulation increases systemic
      glucose tolerance in normal-weight men. In obesity, fundamental reductions in
      brain energy levels, gray matter density, and cortical metabolism, as well as
      chronically impaired glucose tolerance, suggest that disturbed neuroenergetic
      regulation may be involved in the development of overweight and obesity. Here, we
      induced neuronal excitation by anodal transcranial direct current stimulation
      versus sham, examined cerebral energy consumption with (31)P magnetic resonance
      spectroscopy, and determined systemic glucose uptake by euglycemic
      hyperinsulinemic glucose clamp in 15 normal-weight and 15 obese participants. We
      demonstrate blunted brain energy consumption and impaired systemic glucose uptake
      in obese compared with normal-weight volunteers, indicating neuroenergetic
      dysregulation in obese humans. Broadening our understanding of reduced multifocal
      gray matter volumes in obesity, our findings show that reduced appetite- and
      taste-processing area morphometry is associated with decreased brain energy
      levels. Specifically, gray matter volumes of the insula relate to brain energy
      content in obese participants. Overall, our results imply that a diminished
      cerebral energy supply may underlie the decline in brain areas assigned to food
      intake regulation and therefore the development of obesity.

PMID- 25576053
TI  - BAMBI elimination enhances alternative TGF-beta signaling and glomerular
      dysfunction in diabetic mice.
AB  - BMP, activin, membrane-bound inhibitor (BAMBI) acts as a pseudo-receptor for the
      transforming growth factor (TGF)-beta type I receptor family and a negative
      modulator of TGF-beta kinase signaling, and BAMBI(-/-) mice show mild endothelial
      dysfunction. Because diabetic glomerular disease is associated with TGF-beta
      overexpression and microvascular alterations, we examined the effect of diabetes
      on glomerular BAMBI mRNA levels. In isolated glomeruli from biopsies of patients
      with diabetic nephropathy and in glomeruli from mice with type 2 diabetes, BAMBI
      was downregulated. We then examined the effects of BAMBI deletion on
      streptozotocin-induced diabetic glomerulopathy in mice. BAMBI(-/-) mice developed
      more albuminuria, with a widening of foot processes, than BAMBI(+/+) mice, along
      with increased activation of alternative TGF-beta pathways such as extracellular
      signal-related kinase (ERK)1/2 and Smad1/5 in glomeruli and cortices of BAMBI(-/
      ) mice. Vegfr2 and Angpt1, genes controlling glomerular endothelial stability,
      were downmodulated in glomeruli from BAMBI(-/-) mice with diabetes. Incubation of
      glomeruli from nondiabetic BAMBI(+/+) or BAMBI(-/-) mice with TGF-beta resulted
      in the downregulation of Vegfr2 and Angpt1, effects that were more pronounced in
      BAMBI(-/-) mice and were prevented by a MEK inhibitor. The downregulation of
      Vegfr2 in diabetes was localized to glomerular endothelial cells using a histone
      yellow reporter under the Vegfr2 promoter. Thus, BAMBI modulates the effects of
      diabetes on glomerular permselectivity in association with altered ERK1/2 and
      Smad1/5 signaling. Future therapeutic interventions with inhibitors of
      alternative TGF-beta signaling may therefore be of interest in diabetic
      nephropathy.

PMID- 25576054
TI  - Overweight in mice and enhanced adipogenesis in vitro are associated with lack of
      the hedgehog coreceptor boc.
AB  - Obesity arises from a combination of genetic, environmental, and behavioral
      factors. However, the processes that regulate white adipose tissue (WAT)
      expansion at the level of the adipocyte are not well understood. The Hedgehog
      (HH) pathway plays a conserved role in adipogenesis, inhibiting fat formation in
      vivo and in vitro, but it has not been shown that mice with reduced HH pathway
      activity have enhanced adiposity. We report that mice lacking the HH coreceptor
      BOC displayed age-related overweight and excess WAT. They also displayed
      alterations in some metabolic parameters but normal food intake. Furthermore,
      they had an exacerbated response to a high-fat diet, including enhanced weight
      gain and adipocyte hypertrophy, livers with greater fat accumulation, and
      elevated expression of genes related to adipogenesis, lipid metabolism, and
      adipokine production. Cultured Boc(-/-) mouse embryo fibroblasts showed enhanced
      adipogenesis relative to Boc(+/+) cells, and they expressed reduced levels of HH
      pathway target genes. Therefore, a loss-of-function mutation in an HH pathway
      component is associated with WAT accumulation and overweight in mice. Variant
      alleles of such HH regulators may contribute to WAT accumulation in human
      individuals with additional genetic or lifestyle-based predisposition to obesity.

PMID- 25576055
TI  - Enhancement of hypothalamic STAT3 acetylation by nuclear receptor Nur77 dictates
      leptin sensitivity.
AB  - Leptin, an anorexigenic hormone in the hypothalamus, suppresses food intake and
      increases energy expenditure. Failure to respond to leptin will lead to obesity.
      Here, we discovered that nuclear receptor Nur77 expression is lower in the
      hypothalamus of obese mice compared with normal mice. Injection of leptin results
      in significant reduction in body weight in wild-type mice but not in Nur77
      knockout (KO) littermates or mice with specific Nur77 knockdown in the
      hypothalamus. Hypothalamic Nur77 not only participates in leptin central control
      of food intake but also expands leptin's reach to liver and adipose tissues to
      regulate lipid metabolism. Nur77 facilitates signal transducer and activator of
      transcription 3 (STAT3) acetylation by recruiting acetylase p300 and
      disassociating deacetylase histone deacetylase 1 (HDAC1) to enhance the
      transcriptional activity of STAT3 and consequently modulates the expression of
      downstream gene Pomc in the hypothalamus. Nur77 deficiency compromises response
      to leptin in mice fed a high-fat diet. Severe leptin resistance in Nur77 KO mice
      with increased appetite, lower energy expenditure, and hyperleptinemia
      contributes to aging-induced obesity. Our study opens a new avenue for regulating
      metabolism with Nur77 as the positive modulator in the leptin-driven antiobesity
      in the hypothalamus.

PMID- 25576056
TI  - Liver-specific expression of dominant-negative transcription factor 7-like 2
      causes progressive impairment in glucose homeostasis.
AB  - Investigations on the metabolic role of the Wnt signaling pathway and hepatic
      transcription factor 7-like 2 (TCF7L2) have generated opposing views. While some
      studies demonstrated a repressive effect of TCF7L2 on hepatic gluconeogenesis, a
      recent study using liver-specific Tcf7l2(-/-) mice suggested the opposite. As a
      consequence of redundant and bidirectional actions of transcription factor (TCF)
      molecules and other complexities of the Wnt pathway, knockout of a single Wnt
      pathway component may not effectively reveal a complete metabolic picture of this
      pathway. To address this, we generated the liver-specific dominant-negative (DN)
      TCF7L2 (TCF7L2DN) transgenic mouse model LTCFDN. These mice exhibited progressive
      impairment in response to pyruvate challenge. Importantly, LTCFDN hepatocytes
      displayed elevated gluconeogenic gene expression, gluconeogenesis, and loss of
      Wnt-3a-mediated repression of gluconeogenesis. In C57BL/6 hepatocytes, adenovirus
      mediated expression of TCF7L2DN, but not wild-type TCF7L2, increased
      gluconeogenesis and gluconeogenic gene expression. Our further mechanistic
      exploration suggests that TCF7L2DN-mediated inhibition of Wnt signaling causes
      preferential interaction of beta-catenin (beta-cat) with FoxO1 and increased
      binding of beta-cat/FoxO1 to the Pck1 FoxO binding site, resulting in the
      stimulation of Pck1 expression and increased gluconeogenesis. Together, our
      results using TCF7L2DN as a unique tool revealed that the Wnt signaling pathway
      and its effector beta-cat/TCF serve a beneficial role in suppressing hepatic
      gluconeogenesis.

PMID- 25576057
TI  - Selective IL-2 responsiveness of regulatory T cells through multiple intrinsic
      mechanisms supports the use of low-dose IL-2 therapy in type 1 diabetes.
AB  - Low-dose interleukin-2 (IL-2) inhibited unwanted immune responses in several
      clinical settings and is currently being tested in patients with type 1 diabetes
      (T1D). Low-dose IL-2 selectively targets regulatory T cells (Tregs), but the
      mechanisms underlying this selectivity are poorly understood. We show that IL-2
      dependent STAT5 activation in Tregs from healthy individuals and patients with
      T1D occurred at an ~10-fold lower concentration of IL-2 than that required by T
      memory (TM) cells or by in vitro-activated T cells. This selective Treg
      responsiveness is explained by their higher expression of IL-2 receptor subunit
      alpha (IL-2Ralpha) and gamma chain and also endogenous serine/threonine
      phosphatase protein phosphates 1 and/or 2A activity. Genome-wide profiling
      identified an IL-2-dependent transcriptome in human Tregs. Quantitative
      assessment of selected targets indicated that most were optimally activated by a
      100-fold lower concentration of IL-2 in Tregs versus CD4(+) TM cells. Two such
      targets were selectively increased in Tregs from T1D patients undergoing low-dose
      IL-2 therapy. Thus, human Tregs possess an IL-2-dependent transcriptional
      amplification mechanism that widens their selective responses to low IL-2. Our
      findings support a model where low-dose IL-2 selectively activates Tregs to
      broadly induce their IL-2/IL-2R gene program and provide a molecular underpinning
      for low-dose IL-2 therapy to enhance Tregs for immune tolerance in T1D.

PMID- 25576058
TI  - Metformin and Rapamycin Reduce Pancreatic Cancer Growth in Obese Prediabetic Mice
      by Distinct MicroRNA-Regulated Mechanisms.
AB  - Metformin treatment is associated with a decreased risk and better prognosis of
      pancreatic cancer (PC) in patients with type 2 diabetes, but the mechanism of
      metformin's PC growth inhibition in the context of a prediabetic state is
      unknown. We used a Panc02 pancreatic tumor cell transplant model in diet-induced
      obese (DIO) C57BL/6 mice to compare the effects of metformin and the direct
      mammalian target of rapamycin (mTOR) inhibitor rapamycin on PC growth, glucose
      regulation, mTOR pathway signaling, and candidate microRNA (miR) expression. In
      DIO/prediabetic mice, metformin and rapamycin significantly reduced pancreatic
      tumor growth and mTOR-related signaling. The rapamycin effects centered on
      decreased mTOR-regulated growth and survival signaling, including increased
      expression of let-7b and cell cycle-regulating miRs. Metformin (but not
      rapamycin) reduced glucose and insulin levels and expression of miR-34a and its
      direct targets Notch, Slug, and Snail. Metformin also reduced the number and size
      of Panc02 tumor spheres in vitro and inhibited the expression of Notch in
      spheroids. Our results suggest that metformin and rapamycin can both inhibit
      pancreatic tumor growth in obese, prediabetic mice through shared and distinct
      mechanisms. Metformin and direct mTOR inhibitors, alone or possibly in
      combination, represent promising intervention strategies for breaking the
      diabetes-PC link. 

PMID- 25576059
TI  - A mutant allele encoding DNA binding-deficient FoxO1 differentially regulates
      hepatic glucose and lipid metabolism.
AB  - Insulin signaling in the liver blunts glucose production and stimulates
      triglyceride biosynthesis. FoxO1 is required for cAMP induction of hepatic
      glucose production and is permissive for the effect of insulin to suppress this
      process. Moreover, FoxO1 ablation increases lipogenesis. In this study, we
      investigated the pleiotropic actions of FoxO1 on glucose and lipid metabolism. To
      this end, we reconstituted FoxO1 function in mice with a liver-specific deletion
      of Foxo1 using targeted knock-in of an allele encoding a DNA binding-deficient
      FoxO1 mutant (L-DBD). Chow-reared L-DBD mice showed defects in hepatic glucose
      production but normal liver triglyceride content despite increased rates of de
      novo lipogenesis and impaired fatty acid oxidation in isolated hepatocytes. Gene
      expression studies indicated that FoxO1 regulates the expression of glucokinase
      via a cell-nonautonomous coregulatory mechanism, while its regulation of glucose
      6-phosphatase proceeds via a cell-autonomous action as a direct transcriptional
      activator. These conclusions support a differential regulation of hepatic glucose
      and lipid metabolism by FoxO1 based on the mechanism by which it alters the
      expression of key target genes involved in each process.

PMID- 25576060
TI  - Effects of intranasal insulin on hepatic fat accumulation and energy metabolism
      in humans.
AB  - Studies in rodents suggest that insulin controls hepatic glucose metabolism
      through brain-liver crosstalk, but human studies using intranasal insulin to
      mimic central insulin delivery have provided conflicting results. In this
      randomized controlled crossover trial, we investigated the effects of intranasal
      insulin on hepatic insulin sensitivity (HIS) and energy metabolism in 10 patients
      with type 2 diabetes and 10 lean healthy participants (CON). Endogenous glucose
      production was monitored with [6,6-(2)H2]glucose, hepatocellular lipids (HCLs),
      ATP, and inorganic phosphate concentrations with (1)H/(31)P magnetic resonance
      spectroscopy. Intranasal insulin transiently increased serum insulin levels
      followed by a gradual lowering of blood glucose in CON only. Fasting HIS index
      was not affected by intranasal insulin in CON and patients. HCLs decreased by 35%
      in CON only, whereas absolute hepatic ATP concentration increased by 18% after 3
      h. A subgroup of CON received intravenous insulin to mimic the changes in serum
      insulin and blood glucose levels observed after intranasal insulin. This resulted
      in a 34% increase in HCLs without altering hepatic ATP concentrations. In
      conclusion, intranasal insulin does not affect HIS but rapidly improves hepatic
      energy metabolism in healthy humans, which is independent of peripheral
      insulinemia. These effects are blunted in patients with type 2 diabetes.

PMID- 25576061
TI  - Insulin resistance predicts medial temporal hypermetabolism in mild cognitive
      impairment conversion to Alzheimer disease.
AB  - Alzheimer disease (AD) is characterized by progressive hypometabolism on [(18)F]
      fluorodeoxyglucose positron emission tomography (FDG-PET) scans. Peripheral
      insulin resistance (IR) increases AD risk. No studies have examined associations
      between FDG metabolism and IR in mild cognitive impairment (MCI) and AD, as well
      as MCI conversion to AD. We studied 26 cognitively normal (CN), 194 MCI (39 MCI
      progressors, 148 MCI-stable, 2 years after baseline), and 60 AD subjects with
      baseline FDG-PET from the Alzheimer's Disease Neuroimaging Initiative. Mean FDG
      metabolism was derived for AD-vulnerable regions of interest (ROIs), including
      lateral parietal and posteromedial cortices, medial temporal lobe (MTL),
      hippocampus, and ventral prefrontal cortices (vPFC), as well as postcentral gyrus
      and global cerebrum control regions. The homeostasis model assessment of IR (HOMA
      IR) was used to measure IR. For AD, higher HOMA-IR predicted lower FDG in all
      ROIs. For MCI-progressors, higher HOMA-IR predicted higher FDG in the MTL and
      hippocampus. Control regions showed no associations. Higher HOMA-IR predicted
      hypermetabolism in MCI-progressors and hypometabolism in AD in medial temporal
      regions. Future longitudinal studies should examine the pathophysiologic
      significance of the shift from MTL hyper- to hypometabolism associated with IR.

PMID- 25576063
TI  - Letter to: "Vitamin D levels and bone mass in rheumatoid arthritis".

PMID- 25576062
TI  - Foregut exclusion disrupts intestinal glucose sensing and alters portal nutrient
      and hormonal milieu.
AB  - The antidiabetes effects of Roux-en-Y gastric bypass (RYGB) are well-known, but
      the underlying mechanisms remain unclear. Isolating the proximal small intestine,
      and in particular its luminal glucose sensors, from the nutrient stream has been
      proposed as a critical change, but the pathways involved are unclear. In a rodent
      model, we tested the effects of isolating and then stimulating a segment of
      proximal intestine using glucose analogs to examine their impact on glucose
      absorption (Gabsorp) and hormone secretion after a glucose bolus into the distal
      jejunum. Analogs selective for sodium-glucose cotransporter (SGLT) family members
      and the sweet taste receptor were tested, and measurements of the portosystemic
      gradient were used to determine Gabsorp and hormone secretion, including GLP-1.
      Proximal intestinal isolation reduced Gabsorp and GLP-1 secretion. Stimulation of
      the glucose-sensing protein SGLT3 increased Gabsorp and GLP-1 secretion. These
      effects were abolished by vagotomy. Sweet taste receptor stimulation only
      increased GLP-1 secretion. This study suggests a novel role for SGLT3 in
      coordinating intestinal function, as reflected by the concomitant modulation of
      Gabsorp and GLP-1 secretion, with these effects being mediated by the vagus
      nerve. Our findings provide potential mechanistic insights into foregut exclusion
      in RYGB and identify SGLT3 as a possible antidiabetes therapeutic target.

PMID- 25576064
TI  - Skills, expertise and role of Australian emergency clinicians in caring for
      people with advanced cancer.
AB  - OBJECTIVES: To explore the views of Australian emergency department (ED)
      clinicians about their skills, role and expertise in caring for people with
      advanced cancer. METHODS: A cross-sectional electronic survey of doctors and
      nurses working in Australian EDs was undertaken. Comparisons were made by
      demographics and whether respondents had received palliative care education.
      RESULTS: The sample comprised 444 doctors (response rate 13.5%), the majority
      Fellows (emergency medicine specialists) of the Australasian College for
      Emergency Medicine, and 237 nurses, from all states, territories and regions
      (metropolitan and regional). A minority (n=123, 20.6%) felt that the ED was not
      an appropriate place for patients with advanced cancer to present for acute care,
      while almost two-thirds (n=397, 64.8%) found caring for such patients rewarding,
      particularly nurses and those who had received palliative care education; very
      few (n=40, 6.5%) reported feeling uncomfortable talking to the families of dying
      patients. A minority (n=129, 21.0%) felt that it was not appropriate for junior
      medical staff to assess these patients, nurses much more than doctors (42.9% vs
      8.5%, p<0.001). Over half (n=338, 55.1%) felt sufficiently skilled in managing
      pain for people with advanced cancer, with Fellows, more experienced doctors, and
      those who had received palliative care education more likely to feel skilled.
      CONCLUSIONS: ED clinicians in Australia, particularly those who have received
      palliative care education, feel comfortable and adequately skilled in managing
      people with advanced cancer presenting to EDs, and most find it rewarding. The
      importance of palliative care education to emergency clinicians' training should
      be recognised.

PMID- 25576065
TI  - Isotonic versus hypotonic saline solution for maintenance intravenous fluid
      therapy in children: a systematic review.
AB  - BACKGROUND: The administration of hypotonic saline solution for maintenance
      intravenous fluid (IVF) therapy has been the standard of care, but recent
      evidence has shown this treatment to be associated with hyponatremia-related
      complications. The aim of this systematic review was to determine which IVF,
      i.e., a hypotonic or an isotonic saline solution, poses less risk for the
      development of hyponatremia among hospitalized children who require maintenance
      IVF therapy. METHODS: Medline, Cochrane Library, LILACS, Current Controlled
      Trials, reference lists, and abstract proceedings were searched for randomized
      controlled trials (RCTs) comparing hypotonic and isotonic saline solutions for
      maintenance IVF therapy in hospitalized children. Two reviewers independently
      assessed all potentially relevant studies and subsequently extracted data and
      evaluated the methodological quality of the RCTs. Studies were then combined and
      analyzed using a random effects model. RESULTS: Eleven RCTs met the inclusion
      criteria. Our analysis of these 11 RCTs showed that among hospitalized children
      receiving maintenance IVF therapy, isotonic solutions significantly decreased the
      risk of developing hyponatremia [relative risk (RR) 0.50, 95% confidence interval
      (CI) 0.40-0.62] without significantly increasing the risk for hypernatremia (RR
      0.83, 95% CI 0.41-1.67). CONCLUSIONS: Current evidence does not support the
      standard practice of prescribing a hypotonic saline solution as maintenance IVF
      therapy to hospitalized children. Although there is no single IVF composition
      ideal for all children, an isotonic saline solution does appear to be the safer
      choice when maintenance IVF therapy is used in the general pediatric population.

PMID- 25576066
TI  - Positive role of rituximab in switching from cyclosporine to mycophenolate
      mofetil for children with high-dose steroid-dependent nephrotic syndrome.
AB  - BACKGROUND: Recent randomized studies indicate that mycophenolate mofetil (MMF)
      is inferior to cyclosporine (CsA) in preventing relapses of nephrotic syndrome
      (NS). During the last decade, rituximab (RTX) has emerged as a rescue therapy in
      patients with complicated, frequently relapsing, or steroid-dependent NS. CASE
      DIAGNOSIS/TREATMENT: After introducing RTX in our single center, we analyzed 26
      patients with steroid-dependent NS who had relapses while receiving long-term CsA
      and who were subsequently switched to MMF. MMF was adjusted to maintain a
      targeted predose mycophenolic acid (MPA) level of 2-5 MUg/ml. Moreover, for
      patients who required MMF and high-dose prednisolone (PSL) to maintain remission,
      a single infusion of RTX (375 mg/m(2)) was added. The primary endpoint was the
      probability of achieving PSL-free remission for >1 year. At a mean follow-up of
      28.8 +/- 9.9 months, 11 of 26 patients (42 %) required RTX treatment, and 22 of
      those patients (85 %) achieved PSL-free sustained remission. The mean predose MPA
      levels for patients who achieved PSL-free sustained remission were significantly
      higher compared with those for patients who did not (3.1 MUg/ml vs. 1.7 MUg/ml, p
      < 0.05). CONCLUSIONS: After RTX introduction, most patients were able to switch
      from CsA to MMF and achieve sustained PSL-free remission.

PMID- 25576067
TI  - A novel use of a statewide telecolposcopy network for recruitment of participants
      in a Phase I clinical trial of a human papillomavirus therapeutic vaccine.
AB  - BACKGROUND: Historically, recruitment and retention of young women in
      intervention-based clinical trials have been challenging. In August 2012,
      enrollment for a clinical trial testing of an investigational human
      papillomavirus therapeutic vaccine called PepCan was opened at our institution.
      This study was an open-label, single-arm, single-institution, dose-escalation
      Phase I clinical trial. Women with recent Papanicolaou smear results showing high
      grade squamous intraepithelial lesions or results that could not rule out high
      grade squamous intraepithelial lesion were eligible to enroll. Patients with
      biopsy-confirmed high-grade squamous intraepithelial lesion were also eligible.
      Colposcopy was performed at the screening visit, and participants became eligible
      for vaccination when the diagnosis of high-grade squamous intraepithelial lesion
      was confirmed with biopsy and other inclusion criteria were met. The aim of this
      study was to identify strategies and factors effective in recruitment and
      retention of study participants. METHODS: Potential vaccine candidates were
      recruited through direct advertisement as well as referrals, including referrals
      through the Arkansas telecolposcopy network. The network is a federally funded
      program, administered by physicians and advanced practice nurses. The network
      telemedically links rural health sites and allows physician-guided colposcopy and
      biopsies to be conducted by advanced practice nurses. A variety of strategies
      were employed to assure good retention, including face-to-face contact with the
      study coordinator at the time of consent and most of study visits; frequent
      contact using text messaging, phone calls, and e-mails; and creation of a private
      Facebook page to improve communication among research staff and study
      participants. A questionnaire, inquiring about motivation for joining the study,
      occupation, education, household income, number of children, and number of sexual
      partners, was administered at the screening visit with the intent of identifying
      factor(s) associated with recruitment and retention. RESULTS: A total of 37
      participants were enrolled between September 2012 and March 2014. The largest
      proportion of participants (46%) was enrolled from the telecolposcopy network.
      Others were enrolled through outside institutions (43%), in-house referrals (8%),
      or direct advertisement (3%). Most participants were motivated to join the study
      to take care of their health issues. Only two participants joined the Facebook
      private page. Of the 24 participants who qualified for vaccination, only 1
      terminated early due to an unanticipated move. CONCLUSION: The availability of a
      large number of potential participants from the telecolposcopy network increased
      recruitment to this clinical trial by 85% over other traditional means of
      recruitment. The telecolposcopy network is not only a means of providing a
      gynecological service to women who otherwise would forego care but also a novel
      and valuable resource in recruiting participants for a clinical trial.

PMID- 25576068
TI  - Automated measurements for individualized heart rate correction of the QT
      interval.
AB  - BACKGROUND: Subject-specific electrocardiographic QT interval correction for
      heart rate is often used in clinical trials with frequent electrocardiographic
      recordings. However, in these studies relatively few 10-s, 12-lead
      electrocardiograms may be available for calculating the individual correction.
      Highly automated QT and RR measurement tools have made it practical to measure
      electrocardiographic intervals on large volumes of continuous electrocardiogram
      data. The purpose of this study was to determine whether an automated method can
      be used in lieu of a manual method. METHODS: In 49 subjects who completed all
      treatments in a four-armed crossover study we compared two methods for derivation
      of individualized rate-correction coefficients: manual measurement on 10-s
      electrocardiograms and automated measurement of QT and RR during continuous 24-h
      electrocardiogram recordings. The four treatments, received by each subject in a
      latin-square randomization sequence were placebo, moxifloxacin, and two doses of
      an investigational drug. RESULTS: Analysis of continuous electrocardiogram data
      yielded a lower standard deviation of QT:RR regression values than the manual
      method, though the differences were not statistically significant. The within
      subject and within-treatment coefficients of variation between the manual and
      automated methods were not significantly different. Corrected QT values from the
      two methods had similar rates of true and false positive identification of
      moxifloxacin's QT prolonging effect. CONCLUSION: An automated method for
      individualized rate correction applied to continuous electrocardiogram data could
      be advantageous in clinical trials, as the automated method is simpler, is based
      upon a much larger volume of data, yields similar results, and requires no human
      over-reading of the measurements.

PMID- 25576069
TI  - Response to commentary: "A comparative study of three-year weight loss and
      outcomes after laparoscopic gastric bypass in patients with 'yellow light'
      psychological clearance".

PMID- 25576070
TI  - Platelet-rich plasma and other cellular strategies in orthopedic surgery.
AB  - The use of biologics in the treatment of musculoskeletal disease has become
      increasingly more common as research studies continue to provide further
      elucidation of their mechanisms in healing. Platelet-rich plasma, patches, growth
      factors, and stem cells are among the many biologics under active investigation
      and have varying levels of success in augmenting surgical or nonoperative
      interventions. However, the limitations of these treatments exist, and clear
      guidelines for their indications and application have yet to be established. Well
      designed clinical trials will help determine the appropriate future use of
      biologics to ensure consistent outcomes. 

PMID- 25576072
TI  - Management of complications after reverse shoulder arthroplasty.
AB  - Reverse total shoulder arthroplasty (RTSA) has become the treatment of choice for
      patients with rotator cuff arthropathy. Complication rate after RTSA has been
      reported to be three to five times that of conventional total shoulder
      arthroplasty. Intraoperative and postoperative complications include neurological
      injury, infection, dislocation or instability, acromial or scapular spine
      fracture, hematoma, and scapular notching. Knowledge of optimal component
      placement along with preoperative planning and recognition of risk factors are
      essential in optimizing patient outcome. The purpose of this review article is to
      identify the most common and serious complications associated with the RTSA and
      discuss the current methods of management. Complications after RTSA pose a
      significant challenge for healthcare providers and economic burden to society.
      Therefore, it is essential to make the proper diagnosis and develop and implement
      early management plans to improve patient outcome and satisfaction. 

PMID- 25576071
TI  - Management of complications after revision shoulder arthroplasty.
AB  - Complications after revision shoulder arthroplasty are similar to those in the
      primary setting which include instability, fracture, bone loss, infection, nerve
      injury, and loosening. Unlike in the primary setting, however, the rate of
      complications for revisions is significantly greater and the management is more
      complex because of overlapping complications and limited treatment options.
      Furthermore, there is a paucity of evidence-based literature to direct the
      management options in these patients. The purposes of this review are to broadly
      outline the major complications that are seen in revision shoulder arthroplasty
      and to provide general principles on how to recognize and approach these complex
      cases. 

PMID- 25576073
TI  - CHF6001 II: a novel phosphodiesterase 4 inhibitor, suitable for topical pulmonary
      administration--in vivo preclinical pharmacology profile defines a potent anti
      inflammatory compound with a wide therapeutic window.
AB  - CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)
      2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide]
      is a novel phosphodiesterase 4 (PDE4) inhibitor designed for use in pulmonary
      diseases by inhaled administration. Intratracheal administration of CHF6001 to
      ovalbumin-sensitized Brown-Norway rats suppressed the antigen-induced decline of
      lung functions (ED50 = 0.1 umol/kg) and antigen-induced eosinophilia (ED50 = 0.03
      umol/kg) when administered (0.09 MUmol/kg) up to 24 hours before antigen
      challenge, in agreement with CHF6001-sustained lung concentrations up to 72 hours
      after intratracheal treatment (mean residence time 26 hours). Intranasal, once
      daily administration of CHF6001 inhibited neutrophil infiltration observed after
      11 days of tobacco smoke exposure in mice, both upon prophylactic (0.15-0.45
      umol/kg per day) or interventional (0.045-0.45 umol/kg per day) treatment.
      CHF6001 was ineffective in reversing ketamine/xylazine-induced anesthesia (a
      surrogate of emesis in rat) up to 5 umol/kg administered intratracheally, a dose
      50- to 150-fold higher than anti-inflammatory ED50 observed in rats. When given
      topically to ferrets, no emesis and nausea were evident up to 10 to 20 umol/kg,
      respectively, whereas the PDE4 inhibitor GSK-256066 (6-[3
      (dimethylcarbamoyl)phenyl]sulfonyl-4-(3-methoxyanilino)-8-methylquinoline-3
      carboxamide) induced nausea at 1 umol/kg intratracheally. A 14-day inhalation
      toxicology study in rats showed a no-observed-adverse-effect level dose of 4.4
      umol/kg per day for CHF6001, lower than the 0.015 MUmol/kg per day for GSK
      256066. CHF6001 was found effective and extremely well tolerated upon topical
      administration in relevant animal models, and may represent a step forward in
      PDE4 inhibition for the treatment of asthma and chronic obstructive respiratory
      disease. 

PMID- 25576074
TI  - Efficacy and mechanism of action of volasertib, a potent and selective inhibitor
      of Polo-like kinases, in preclinical models of acute myeloid leukemia.
AB  - Polo-like kinase 1 (Plk1), a member of the Polo-like kinase family of
      serine/threonine kinases, is a key regulator of multiple steps in mitosis. Here
      we report on the pharmacological profile of volasertib, a potent and selective
      Plk inhibitor, in multiple preclinical models of acute myeloid leukemia (AML)
      including established cell lines, bone marrow samples from AML patients in short
      term culture, and subcutaneous as well as disseminated in vivo models in immune
      deficient mice. Our results indicate that volasertib is highly efficacious as a
      single agent and in combination with established and emerging AML drugs,
      including the antimetabolite cytarabine, hypomethylating agents (decitabine,
      azacitidine), and quizartinib, a signal transduction inhibitor targeting FLT3.
      Collectively, these preclinical data support the use of volasertib as a new
      therapeutic approach for the treatment of AML patients, and provide a foundation
      for combination approaches that may further improve and prolong clinical
      responses. 

PMID- 25576076
TI  - Use of an adhesive polyurethane film for ear retraction.

PMID- 25576075
TI  - CHF6001 I: a novel highly potent and selective phosphodiesterase 4 inhibitor with
      robust anti-inflammatory activity and suitable for topical pulmonary
      administration.
AB  - This study examined the pharmacologic characterization of CHF6001 [(S)-3,5
      dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3
      (cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide], a
      novel phosphodiesterase (PDE)4 inhibitor designed for treating pulmonary
      inflammatory diseases via inhaled administration. CHF6001 was 7- and 923-fold
      more potent than roflumilast and cilomilast, respectively, in inhibiting PDE4
      enzymatic activity (IC50 = 0.026 +/- 0.006 nM). CHF6001 inhibited PDE4 isoforms A
      D with equal potency, showed an elevated ratio of high-affinity rolipram binding
      site versus low-affinity rolipram binding site (i.e., >40) and displayed >20,000
      fold selectivity versus PDE4 compared with a panel of PDEs. CHF6001 effectively
      inhibited (subnanomolar IC50 values) the release of tumor necrosis factor-alpha
      from human peripheral blood mononuclear cells, human acute monocytic leukemia
      cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383).
      Moreover, CHF6001 potently inhibited the activation of oxidative burst in
      neutrophils and eosinophils, neutrophil chemotaxis, and the release of interferon
      gamma from CD4(+) T cells. In all these functional assays, CHF6001 was more
      potent than previously described PDE4 inhibitors, including roflumilast, UK
      500,001 [2-(3,4-difluorophenoxy)-5-fluoro-N-((1S,4S)-4-(2-hydroxy-5
      methylbenzamido)cyclohexyl)nicotinamide], and cilomilast, and it was comparable
      to GSK256066 [6-((3-(dimethylcarbamoyl)phenyl)sulfonyl)-4-((3
      methoxyphenyl)amino)-8-methylquinoline-3-carboxamide]. When administered
      intratracheally to rats as a micronized dry powder, CHF6001 inhibited
      liposaccharide-induced pulmonary neutrophilia (ED50 = 0.205 MUmol/kg) and
      leukocyte infiltration (ED50 = 0.188 MUmol/kg) with an efficacy comparable to a
      high dose of budesonide (1 MUmol/kg i.p.). In sum, CHF6001 has the potential to
      be an effective topical treatment of conditions associated with pulmonary
      inflammation, including asthma and chronic obstructive pulmonary disease. 

PMID- 25576077
TI  - A randomized controlled trial of postoperative pain control after subpectoral
      breast augmentation using intercostal nerve block versus bupivacaine pectoralis
      major infiltration: a pilot study.

PMID- 25576079
TI  - Reduced granulocyte counts in sputum may reflect aggravated disease.

PMID- 25576078
TI  - Maternal smoking during pregnancy and offspring type 1 diabetes mellitus risk:
      accounting for HLA haplotype.
AB  - The main objective of this study was to investigate the risk of type 1 diabetes
      mellitus (T1D) in children exposed to tobacco smoking in utero, also taking
      genetic predisposition as expressed by HLA haplotype into account. In Skane, the
      southernmost county of Sweden, all children born 1999-2005 who developed T1D were
      registered, resulting in 344 cases. For each child with T1D, three control
      children, matched for HLA haplotype and birthyear, were selected. Information on
      prenatal smoking exposure was retrieved from a regional birth register.
      Conditional logistic regressions were used to evaluate T1D risk following
      prenatal smoking exposure. In these data, maternal smoking in early pregnancy was
      associated with a higher risk of her child developing T1D [odds ratio (OR) 2.83;
      95% confidence interval (CI) 1.67-4.80 for 1-9 cigarettes/day, and OR 3.91; 95%
      CI 1.22-12.51 for >9 cigarettes/day]. Results remained through all adjustments
      and sensitivity analyses. When genetic predisposition in terms of HLA haplotype
      was taken into account, we found that children exposed to smoking during fetal
      life were at higher risk of developing T1D in childhood.

PMID- 25576080
TI  - Reply: To PMID 25195169.

PMID- 25576081
TI  - Component-resolved diagnosis of baker's allergy based on specific IgE to
      recombinant wheat flour proteins.
AB  - BACKGROUND: Sensitization to wheat flour plays an important role in the
      development and diagnosis of baker's asthma. OBJECTIVES: We evaluated wheat
      allergen components as sensitizers for bakers with work-related complaints, with
      consideration of cross-reactivity to grass pollen. METHODS: Nineteen recombinant
      wheat flour proteins and 2 cross-reactive carbohydrate determinants were tested
      by using CAP-FEIA in sera of 101 bakers with wheat flour allergy (40 German, 37
      Dutch, and 24 Spanish) and 29 pollen-sensitized control subjects with wheat
      specific IgE but without occupational exposure. IgE binding to the single
      components was inhibited with wheat flour, rye flour, and grass pollen. The
      diagnostic efficiencies of IgE tests with single allergens and combinations were
      evaluated by assessing their ability to discriminate between patients with
      baker's allergy and control subjects based on receiver operating characteristic
      analyses. RESULTS: Eighty percent of bakers had specific IgE levels of 0.35 kUA/L
      or greater and 91% had specific IgE levels of 0.1 kUA/L or greater to at least
      one of the 21 allergens. The highest frequencies of IgE binding were found for
      thiol reductase (Tri a 27) and the wheat dimeric alpha-amylase inhibitor 0.19
      (Tri a 28). Cross-reactivity to grass pollen was proved for 9 components, and
      cross-reactivity to rye flour was proved for 18 components. A combination of IgE
      tests to 5 components, Tri a 27, Tri a 28, tetrameric alpha-amylase inhibitor CM2
      (Tri a 29.02), serine protease inhibitor-like allergen (Tri a 39), and 1-cys
      peroxiredoxin (Tri a 32), produced the maximal area under the curve (AUC = 0.84)
      in receiver operating characteristic analyses, but this was still lower than the
      AUC for wheat- or rye flour-specific IgE (AUC = 0.89 or 0.88, respectively).
      CONCLUSIONS: Component-resolved diagnostics help to distinguish between
      sensitization caused by occupational flour exposure and wheat seropositivity
      based on cross-reactivity to grass pollen. For routine diagnosis of baker's
      allergy, however, allergen-specific IgE tests with whole wheat and rye flour
      extracts remain mandatory because of superior diagnostic sensitivity.

PMID- 25576082
TI  - Sustained high levels of neuroprotective, high molecular weight, phosphorylated
      tau in the longest-lived rodent.
AB  - Tau protein is primarily expressed in neuronal axons and modulates microtubule
      stability. Tau phosphorylation, aggregation, and subcellular mislocalization
      coincide with neurodegeneration in numerous diseases, including Alzheimer's
      disease (AD). During AD pathogenesis, tau misprocessing accompanies Abeta
      accumulation; however, AD animal models, despite elevated Abeta, fail to develop
      tauopathy. To assess whether lack of tau pathology is linked to short life span
      common to most AD models, we examined tau processing in extraordinarily long
      lived, mouse-sized naked mole-rats (NMRs; approximately 32 years), which express
      appreciable levels of Abeta throughout life. We found that NMRs, like other
      mammals, display highest tau phosphorylation during brain development. Although
      tau phosphorylation decreases with aging, unexpectedly adult NMRs have higher
      levels than transgenic mice overexpressing mutant human tau. However, in sharp
      contrast with the somatodendritic accumulation of misprocessed tau in the
      transgenic mice, NMRs maintain axonal tau localization. Intriguingly, the adult
      NMR tau protein is 88 kDa, much larger than 45-68 kDa tau expressed in other
      mammals. We propose that this 88 kDa tau protein may offer exceptional
      microtubule stability and neuroprotection against lifelong, elevated Abeta.

PMID- 25576083
TI  - Redundancy: a critical obstacle to improving cancer therapy.
AB  - A system characterized by redundancy has various elements that are able to act in
      the same biologic or dynamic manner, where the inhibition of one of those
      elements has no significant effect on the global biologic outcome or on the
      system's dynamic behavior. Methods that aim to predict the effectiveness of
      cancer therapies must include evolutionary and dynamic features that would change
      the static view that is widely accepted. Here, we explore several important
      issues about mechanisms of redundancy, heterogeneity, biologic importance, and
      drug resistance and describe methodologic challenges that, if overcome, would
      significantly contribute to cancer research.

PMID- 25576084
TI  - Interferon regulatory factor-1 signaling regulates the switch between autophagy
      and apoptosis to determine breast cancer cell fate.
AB  - Interferon regulatory factor-1 (IRF1) is a tumor suppressor that regulates cell
      fate in several cell types. Here, we report an inverse correlation in expression
      of nuclear IRF1 and the autophagy regulator ATG7 in human breast cancer cells
      that directly affects their cell fate. In mice harboring mutant Atg7, nuclear
      IRF1 was increased in mammary tumors, spleen, and kidney. Mechanistic
      investigations identified ATG7 and the cell death modulator beclin-1 (BECN1) as
      negative regulators of IRF1. Silencing ATG7 or BECN1 caused estrogen receptor
      alpha to exit the nucleus at the time when IRF1 nuclear localization occurred.
      Conversely, silencing IRF1 promoted autophagy by increasing BECN1 and blunting
      IGF1 receptor and mTOR survival signaling. Loss of IRF1 promoted resistance to
      antiestrogens, whereas combined silencing of ATG7 and IRF1 restored sensitivity
      to these agents. Using a mathematical model to prompt signaling hypotheses, we
      developed evidence that ATG7 silencing could resensitize IRF1-attenuated cells to
      apoptosis through mechanisms that involve other estrogen-regulated genes.
      Overall, our work shows how inhibiting the autophagy proteins ATG7 and BECN1 can
      regulate IRF1-dependent and -independent signaling pathways in ways that engender
      a new therapeutic strategy to attack breast cancer.

PMID- 25576085
TI  - The relationship between pain, fatigue, depression and functional performance in
      stable heart failure.
AB  - OBJECTIVE: Evaluate the relationship between pain, fatigue, depression,
      demographic, clinical, and functional variables in stable heart failure (HF).
      BACKGROUND: Pain, fatigue and depression are common in HF. Little is known about
      the relationship between pain, fatigue and depression and functional measures in
      this population. METHODS: Secondary data analysis of a cross sectional study of
      173 stable HF patients. Associations between clinical and demographic factors,
      pain (SF-36), depression (CES-D), and fatigue (MAF) to functional performance and
      capacity (SF-36 role limitations due to physical functioning and 6-Minute Walk
      Test) were evaluated using hierarchical multiple regressions. RESULTS: The sample
      was 65% male with a mean age of 60. Fifty-seven percent (n = 100) had pain, 54%
      (n = 94) had fatigue, and 46% (n = 79) had depression. Pain, depression and
      fatigue were negatively associated with functional performance but not functional
      capacity when controlling for demographic and clinical covariates. CONCLUSIONS:
      Pain, fatigue and depression were associated with decreased functional
      performance in stable HF. Symptom management interventions are needed in HF.

PMID- 25576086
TI  - Predictors for identifying patients with patellofemoral pain syndrome responding
      to femoral nerve mobilization.
AB  - OBJECTIVE: To identify the predictors for successful neurodynamic management in
      patients with patellofemoral pain syndrome. DESIGN: Prospective cohort,
      prediction rule study. SETTING: Hospital. PARTICIPANTS: Patients with
      patellofemoral pain syndrome (N=51) underwent clinical examination and
      measurement of physical parameters, including femoral slump test, lower-extremity
      alignment, flexibility and muscle strength, and functional level. INTERVENTION:
      Patients received 6 treatment sessions of femoral nerve mobilization within 2
      weeks. MAIN OUTCOME MEASURES: Pain level during functional testing was assessed
      before and after the first and sixth session of treatment. Patients were then
      grouped into responder and nonresponder groups. Criteria for the responder group
      was a pain score decrease >=50% or Global Rating Scale score >=4. Chi-square and
      independent t tests were used to identify potential variables with a significance
      level of .10, and stepwise logistic regression was used to find predictors with a
      significance level of .05. RESULTS: Twenty-five patients responded to the initial
      treatment (immediate effect), and 28 patients responded after 6 sessions (longer
      term effect). A positive femoral slump test was identified as the predictor for
      the immediate treatment effect. The prediction factors for the longer-term effect
      included responding to femoral nerve mobilization the first time and a bilateral
      difference in hip extension angles. Application of the clinical predictors
      improved the success rate to 90% for 1 treatment session and 93% for 6 treatment
      sessions. CONCLUSIONS: Clinicians could use the positive femoral slump test and a
      bilateral difference in hip extension angles during the femoral slump test to
      determine whether or not patients with patellofemoral pain syndrome might benefit
      from femoral nerve mobilization.

PMID- 25576087
TI  - Ramp-related incidents involving wheeled mobility device users during transit bus
      boarding/alighting.
AB  - OBJECTIVES: To estimate the prevalence of wheeled mobility device (WhMD) ramp
      related incidents while boarding/alighting a public transit bus and to determine
      whether the frequency of incidents is less when the ramp slope meets the proposed
      Americans with Disabilities Act (ADA) maximum allowable limit of <=9.5 degrees .
      DESIGN: Observational study. SETTING: Community public transportation.
      PARTICIPANTS: WhMD users (N=414) accessing a public transit bus equipped with an
      instrumented ramp. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Prevalence of boarding/alighting incidents involving WhMD users and associated
      ramp slopes; factors affecting incidents. RESULTS: A total of 4.6% (n=35) of WhMD
      users experienced an incident while boarding/alighting a transit bus.
      Significantly more incidents occurred during boarding (6.3%, n=26) than during
      alighting (2.2%, n=9) (P<.01), and when the ramp was deployed to street level
      (mean slope=11.4 degrees ) compared with sidewalk level (mean slope=4.2 degrees )
      (P=.01). The odds ratio for experiencing an incident when the ramp slope exceeded
      the proposed ADA maximum allowable ramp slope was 5.4 (95% confidence interval,
      2.4-12.2; P<.01). The odds ratio for assistance being rendered to board/alight
      when the ramp slope exceeded the proposed ADA maximum allowable ramp slope was
      5.1 (95% confidence interval, 2.9-9.0; P<.01). CONCLUSIONS: The findings of this
      study support the proposed ADA maximum allowable ramp slope of 9.5 degrees . Ramp
      slopes >9.5 degrees  and ramps deployed to street level are associated with a
      higher frequency of incidents and provision of assistance. Transit agencies
      should increase awareness among bus operators of the effect kneeling and
      deployment location (street/sidewalk) have on the ramp slope. In addition, ramp
      components and the built environment may contribute to incidents. When
      prescribing WhMDs, skills training must include ascending/descending ramps at
      slopes encountered during boarding/alighting to ensure safe and independent
      access to public transit buses.

PMID- 25576088
TI  - Alzheimer's disease: current and future therapy.

PMID- 25576089
TI  - A pivotal moment in Alzheimer's disease and dementia: how global unity of purpose
      and action can beat the disease by 2025.
AB  - The world is at a pivotal moment in the global fight against Alzheimer's disease,
      a disease that by 2013 affected 44.4 million people globally and is expected to
      affect 75.6 million by 2030. France, Australia, Japan, US and Great Britain are
      among the countries that have adopted national policies to address the growing
      numbers. Multilateral organizations have also prioritized the disease, and
      possibly most significantly, the G8, under British Prime Minister David Cameron's
      leadership, set its focus on dementia starting December 2013. Despite the growing
      attention, the response has not been commensurate with the urgency of the
      situation, and we need to promote comprehensive collaboration that catalyzes the
      development of new treatments, initiates the creation of innovative financial
      models for research and drives the utilization of technological innovation with
      the aim to reverse the trajectory of this devastating disease. 

PMID- 25576090
TI  - Mechanistic time scales in adhesive mixing investigated by dry particle sizing.
AB  - This study exploits the mechanisms governing blending of adhesive mixtures, i.e.
      random mixing, de-agglomeration and adhesion, and their relative importance to
      achieve mixing homogeneity. To this end, blending of micronized particles (fines)
      with carrier particles was carried out using a high shear mixer. Dry particle
      sizing using laser diffraction coupled with a strong powder dispersion unit was
      employed to measure the fines content in samples collected during mixing, and
      hence to assess blend homogeneity. The method was also employed to evaluate the
      relative strength of the agglomerates present in the fines. Particle sizing using
      a non-destructive imaging technique was used to monitor changes in particle size
      during blending. It could be shown that the de-agglomeration of the fine-particle
      agglomerates is the slowest mechanism and hence the rate-limiting step as regards
      achieving a homogeneous adhesive mixture. Consequently, a longer mixing time is
      needed for blending of larger agglomerates. Being fast, simple and reproducible,
      the laser diffraction technique was shown to be an efficient method for
      measurement of fine particle content and homogeneity of a mixture, while the non
      destructive image analysis was able to give relevant information on the rate of
      de-agglomeration of the fine-particle agglomerates as well as on the size of the
      resulting carrier-fine particle assemblies. 

PMID- 25576091
TI  - Monocular deprivation delays the dynamic changes of phosphorylated synapsin Ia/b
      at site-1 in contralateral visual cortex of juvenile mice.
AB  - Synapsins as a family of presynaptic terminal phosphoprotein participates in
      neuronal development, but their role in the synaptic plasticity of visual cortex
      is unclear. In this study, the impact of monocular deprivation (MD) on dynamic
      changes of isoform-specific protein expression and site 1 phosphorylation of
      synapsins in visual cortex of the postnatal mice were observed by using the
      technique of Western blot analysis. The results showed that the total (T-)
      protein levels of synapsins including the isoform of Ia/b, IIa/b and IIIa were
      about 21-26% of adult level in visual cortex of mice at postnatal 7 days (P7),
      and then the T-synapsin Ia/b and IIb could quickly reach adult level at P35.
      However, the T-synapsin IIa and IIIa increased more slowly (71-74% at P35), and
      then kept increasing in the visual cortex of mice at P60. Unlike to the changes
      of T-synapsins, the level of phosphorylated (P-) synapsin Ia/b (not IIa/b and
      IIIa) at site 1 increased with development to the highest level at P21, and then
      decreased rapidly to a low level in visual cortex of mice at P35-60. In addition,
      we found that the levels of P-synapsin Ia/b increased significantly in left
      visual cortex of P28 and P35 (not P21 and P42) mice with 1-week MD of right eye;
      and no significant changes of T-synapsins were observed in both left and right
      sides of visual cortex in P21-42 mice with MD treatment. These results suggested
      that the isoform-specific protein expression and site-1 phosphorylation of
      synapsins might play a different role in the synaptic plasticity of visual
      cortex, and MD delays the dynamic changes of phosphorylated synapsin Ia/b at site
      1 in contralateral visual cortex of juvenile mice.

PMID- 25576092
TI  - Necrostatin-1 ameliorates intracerebral hemorrhage-induced brain injury in mice
      through inhibiting RIP1/RIP3 pathway.
AB  - Necroptosis is a recently discovered programmed necrosis, regulated by receptor
      interacting protein kinase 1 (RIP1) and RIP3 after death signal stimulation and
      could be specifically inhibited by necrostatin-1. The aim of this study was to
      investigate the role of RIP1 and RIP3 signal pathways in a mouse model of
      collagenase-induced intracerebral hemorrhage (ICH) and assess the effect of
      necrostatin-1 on brain injury after ICH. We found that RIP1 and RIP3 proteins
      were abundantly expressed and increased in mice brain after ICH. Necrostatin-1
      pretreatment improved neurological function and attenuated brain edema in mice
      after ICH. Moreover, necrostatin-1 reduced RIP1-RIP3 interaction and propidium
      iodide (PI) positive cell death, and further inhibited microglia activation and
      pro-inflammatory mediator genes [tumor necrosis factor-a (TNF-alpha) and
      interleukin-1beta (IL-1beta)] expression after ICH. These findings indicate that
      RIP1/RIP3-mediated necroptosis is an important mechanism of cell death after ICH.
      Through inhibiting necroptosis, necrostatin-1 plays a protective role in reducing
      necrotic cell death after ICH. Necrostatin-1 is a promising therapeutic agent
      that protects cells from necroptosis and improves functional outcome. 

PMID- 25576093
TI  - Comparison of Automated and Manual DNA Isolation Methods for DNA Methylation
      Analysis of Biopsy, Fresh Frozen, and Formalin-Fixed, Paraffin-Embedded
      Colorectal Cancer Samples.
AB  - Automated DNA isolation can decrease hands-on time in routine pathology. Our aim
      was to apply automated DNA isolation and perform DNA methylation analyses. DNA
      isolation was performed manually from fresh frozen (CRC = 10, normal = 10)
      specimens and colonic biopsies (CRC = 10, healthy = 10) with QIAamp DNA Mini Kit
      and from FFPE blocks (CRC = 10, normal = 10) with QIAamp DNA FFPET Kit. Automated
      DNA isolation was performed with MagNA Pure DNA and Viral NA SV kit on MagNA Pure
      96 system. DNA methylation of MAL, SFRP1, and SFRP2 were analyzed with
      methylation-specific high-resolution melting analysis. Yield of automatically
      isolated samples was equal in fresh frozens and significantly lower compared to
      manually isolated biopsy and FFPE samples. OD260/280 of fresh frozen and biopsy
      samples were similar after both isolations, automated isolation resulted in lower
      purity in FFPE samples. Both protocols resulted in similar OD260/230 from fresh
      frozens, automated isolation method was superior in biopsies and manual protocol
      in FFPE samples. DNA methylation of biopsies, fresh frozen samples were highly
      similar after both methods, results of automatically and manually isolated FFPE
      samples were different. Automated DNA isolation from fresh frozen samples can be
      suitable for high-throughput laboratories. 

PMID- 25576094
TI  - Preferential cytotoxicity of bortezomib toward highly malignant human liposarcoma
      cells via suppression of MDR1 expression and function.
AB  - Liposarcoma is the most common soft tissue sarcoma with a high risk of relapse.
      Few therapeutic options are available for the aggressive local or metastatic
      disease. Here, we report that the clinically used proteasome inhibitor bortezomib
      exhibits significantly stronger cytotoxicity toward highly malignant human
      liposarcoma SW872-S cells compared with its parental SW872 cells, which is
      accompanied by enhanced activation of apoptotic signaling both in vitro and in
      vivo. Treatment of cells with Jun-N-terminal kinase (JNK) inhibitor SP60015 or
      the translation inhibitor cycloheximide ameliorated this enhanced apoptosis.
      Bortezomib inhibited MDR1 expression and function more effectively in SW872-S
      cells than in SW872 cells, indicating that the increased cytotoxicity relies on
      the degree of proteasome inhibition. Furthermore, the pharmacological or genetic
      inhibition of sarco/endoplasmic reticulum calcium-ATPase (SERCA) 2, which is
      highly expressed in SW872-S cells, resulted in partial reversal of cell growth
      inhibition and increase of MDR1 expression in bortezomib-treated SW872-S cells.
      These results show that bortezomib exhibits preferential cytotoxicity toward
      SW872-S cells possibly via highly expressed SERCA2-associated MDR1 suppression
      and suggest that bortezomib may serve as a potent agent for treating advanced
      liposarcoma. 

PMID- 25576095
TI  - Maternal taurine supplementation attenuates maternal fructose-induced metabolic
      and inflammatory dysregulation and partially reverses adverse metabolic
      programming in offspring.
AB  - Excessive fructose consumption is associated with insulin resistance (IR) and
      nonalcoholic fatty liver disease (NAFLD), and high fructose intake during
      pregnancy can lead to compromised fetal development in the rat. Evidence suggests
      that the amino acid taurine can ameliorate fructose-induced IR and NAFLD in
      nonpregnant animals. This study investigated the efficacy of taurine
      supplementation on maternal fructose-induced metabolic dysfunction and neonatal
      health. Time-mated Wistar rats were randomized to four groups during pregnancy
      and lactation: (a) control diet (CON), (b) CON supplemented with 1.5% taurine in
      drinking water (CT), (c) CON supplemented with fructose solution (F) and (d) F
      supplemented with taurine (FT). Maternal and neonatal weights, plasma cytokines
      and hepatic gene expression were analyzed. Maternal hyperinsulinemia, increased
      homeostasis model assessment of IR indices and elevated proinflammatory cytokines
      were observed in F group and normalized in FT group. Maternal fructose-induced
      hepatic steatosis accompanied with increased liver weight was ameliorated with
      taurine supplementation. Maternal hepatic sterol regulatory element-binding
      protein-1c and fatty acid synthase expression was significantly increased in the
      F group compared to the CON, CT and FT groups. Neonatal hepatic
      phosphoenolpyruvate carboxykinase expression was increased in male F neonates
      compared to the CON, CT and FT groups and was increased in female F and FT
      neonates compared to CON and CT. Interleukin-1beta expression was decreased in
      male CT and FT neonates compared to other male groups. Hepatic tumour necrosis
      factor receptor-1 was lower in the male FT group than the F group. These results
      demonstrate that maternal taurine supplementation can partially reverse fructose
      induced maternal metabolic dysfunction and may ameliorate adverse developmental
      programming effects in offspring in a sex-specific manner. 

PMID- 25576096
TI  - Sociosexual behaviors during the transition from non-receptivity to receptivity
      in rats housed in a seminatural environment.
AB  - Female behavioral estrus is defined as the period between the first lordosis
      displayed during the estrus cycle to the lordosis that is not followed by another
      within 60 min. In a seminatural environment, an estrous female consistently
      displays lordosis in response to every male mount from the start of behavioral
      estrus until the end of it. This means that the female suddenly changes from a
      state of complete non-receptivity to full receptivity and then abruptly changes
      back to non-receptivity. It is unlikely that these abrupt changes are caused by
      sudden changes in serum concentration of ovarian steroids. Here, we present the
      results of a detailed study of sociosexual behaviors during the transition from
      non-receptivity to receptivity and vice versa. The frequency of male mounting was
      close to zero before and after estrus. It remained at a constant, high level
      throughout estrus. Female paracopulatory behavior and male pursuit of the female
      increased drastically from a very low level before estrus to a high level during
      estrus. They returned to low levels immediately after estrus. None of the many
      other behavior patterns registered changed during the transitions. It appears
      that the sudden increase in male pursuit and female paracopulatory behavior can
      explain the beginning of behavioral estrus, and their equally sudden
      disappearance causes it to end. The neurochemical mechanisms behind these almost
      instantaneous behavioral changes are unknown.

PMID- 25576097
TI  - Antifungal activity of the essential oil of Angelica major against Candida,
      Cryptococcus, Aspergillus and dermatophyte species.
AB  - The composition and antifungal activity of the essential oil (EO) of Angelica
      major and its main components alpha-pinene and cis-beta-ocimene against
      clinically relevant yeasts and moulds were evaluated. EO from the plant's aerial
      parts was obtained by hydrodistillation and analysed by gas chromatography (GC)
      and gas chromatography/mass spectrometry (GC/MS). The oil showed high contents of
      alpha-pinene (21.8 %) and cis-beta-ocimene (30.4 %). Minimum inhibitory
      concentrations (MICs) were measured according to the broth macrodilution
      protocols by the Clinical and Laboratory Standards Institute (CLSI). The EO,
      alpha-pinene and cis-beta-ocimene displayed low MICs and minimum fungicidal
      concentrations (MFCs) against dermatophytes and Cryptococcus neoformans, with
      alpha-pinene being the most active. Regarding Candida species, the EO
      susceptibility profiles seem to be diverse and not correlated with fluconazole
      susceptibility patterns. Moreover, an inhibition of yeast-mycelium transition was
      demonstrated at sub-inhibitory concentrations of the EO, alpha-pinene and cis
      beta-ocimene in C. albicans. In addition, their haemolytic activity was low. The
      activity displayed by A. major EO and its main components associated with low
      cytotoxic activity confirms their potential as an antifungal agent against fungal
      species frequently implicated in human mycoses, particularly cryptococcosis and
      dermatophytosis. The association with commercial antifungal compounds could bring
      benefits, by the effect on germ tube formation, and be used in mucocutaneous
      candidiasis treatment. 

PMID- 25576098
TI  - Knowledge, attitudes and practices regarding rabies and exposure to bats in two
      rural communities in Guatemala.
AB  - BACKGROUND: Rabies is a fatal encephalitis caused by rabies virus, of the genus
      Lyssavirus. The principal reservoir for rabies in Latin America is the common
      vampire bat (Desmodus rotundus), which feeds routinely on the blood of cattle,
      and when livestock are scarce, may prey on other mammals, including humans.
      Although rabies is endemic in common vampire bat populations in Guatemala, there
      is limited research on the extent of exposure to bats among human populations
      living near bat refuges. RESULTS: A random sample of 270 of 473 households (57%)
      in two communities located within 2 Km of a known bat roost was selected and one
      adult from each household was interviewed. Exposure to bats (bites, scratches or
      bare skin contact) was reported by 96 (6%) of the 1,721 residents among the
      selected households. Of those exposed, 40% received rabies post-exposure
      prophylaxis. Four percent of household respondents reported that they would seek
      rabies post exposure prophylaxis if they were bitten by a bat. CONCLUSIONS: These
      findings demonstrate that exposure to bats in communities near bat roosts is
      common but recognition of the potential for rabies transmission from bats is low.
      There is a need for educational outreach to raise awareness of bat-associated
      rabies, prevent exposures to bats and ensure appropriate health-seeking
      behaviours for bat-inflicted wounds, particularly among communities living near
      bat roosts in Guatemala.

PMID- 25576099
TI  - One type of VEGFR is involved in WSSV infection to the Pacific whiteleg shrimp
      Litopenaeus vannamei.
AB  - VEGF signaling pathway plays vital roles in many physiological processes
      including cell proliferation, differentiation, migration, survival, cell-cell
      communication, vessel permeability and virus-host interaction in mammalian
      species. However, the VEGF signaling pathway and its biological function are
      still poorly understood in crustaceans. In the present study, an essential member
      of VEGF signaling pathway, VEGF receptor (LvVEGFR), was isolated from Penaeid
      shrimp Litopenaeus vannamei and its function during virus infection was analyzed.
      The deduced amino acid sequence of LvVEGFR possessed all common features of
      VEGFRs reported in other species, including a signal peptide, six IG-like
      domains, one immunoglobulin subtype 2 domain, a transmembrane domain, a
      juxtamembrane domain, a protein kinase domain separated by a kinase insert
      sequence, one ATP binding site and one tyrosine-protein kinase active site.
      LvVEGFR is mainly expressed in hemocytes and intestine. The transcriptional level
      of LvVEGFR could be obviously up-regulated in hemocytes and intestine after WSSV
      infection. Silencing of LvVEGFR gene by double-strand RNA (dsRNA) interference
      could not only lead to a decrease of virus copy number in WSSV infected shrimp,
      but also reduce the mortality of shrimp during WSSV infection. These data
      suggested that VEGF signaling pathway might play an important role during viral
      infection to shrimp. 

PMID- 25576100
TI  - Effect of double coating of one-step self-etching adhesive on micromorphology and
      microtensile bond strength to sound vs demineralized dentin.
AB  - AIM: The purpose of the present study was to evaluate (1) the one-step adhesive
      system application method (doubling the adhesive coatings) in regard to
      microtensile bond strength (MTB) and (2) the interfacial morphology of one-step
      adhesives to sound vs demineralized dentin. MATERIALS AND METHODS: Forty dentin
      fragments were randomly allocated to 2 groups: D. demineralized dentin and S.
      sound dentin. Specimens were also subdivided into 2 groups (n = 10), according to
      the one-step adhesive [AEO (Adper Easy One), 3M ESPE] application method: M,
      According to the manufacturer's instructions, and D, based on the application of
      two consecutive layers. After adhesive light polymerization, a resin composite
      block (Filtek Z250, 3M ESPE) was built on the dentin surface. Resin-tooth blocks
      were sectioned into 0.9 mm thick slabs, and one slab of each block was prepared
      for adhesive interface analysis by scanning electron microscopy (SEM). The
      remaining slabs were sectioned into 0.8 mm(2) sticks that were subjected to
      tensile stress (0.5 mm/min). Data were subjected to two-way ANOVA and Tukey's
      test (alpha = 0.05). RESULTS: The application of two consecutive layers of AEO
      adhesive system did not Influence MTB values for sound dentin. When two
      consecutive layers of one-step adhesive system were applied, MTB was
      statistically greater in demineralized vs sound dentin. SEM analysis demonstrated
      that the application of two consecutive adhesive layers to sound and
      demineralized dentin produced longer resin tags. CONCLUSION: It can be concluded
      that the application of two consecutive adhesive layers improved bond strength to
      deminera-lized dentin, but no such effect was observed for sound dentin. CLINICAL
      SIGNIFICANCE: Application of double coats of one-step self-etching adhesive
      improved bond strength to demineralized dentin.

PMID- 25576101
TI  - Influence of fluoride concentration and pH Value of 35% hydrogen peroxide on the
      hardness, roughness and morphology of bovine enamel.
AB  - AIM: The aim of this in vitro study was to evaluate the effects of different
      sodium fuoride (NaF) concentrations and pH values on the Knoop hardness (KHN),
      surface roughness (SR), and morphology of bovine incisors bleached with 35%
      hydrogen peroxide (HP). MATERIALS AND METHODS: Sixty-five bovine incisors were
      fragmented (5 mm(2) * 2 mm) and distributed in 5 groups: Control (unbleached),
      Low NaF/Acidic (35% HP + 1.3% NaF, pH 5.5), Low NaF/Neutral (35% HP + 1.3% NaF,
      pH 7.0), High NaF/ Acidic (35% HP + 2% NaF, pH 5.5), and High NaF/Neutral (35% HP
      + 2% NaF, pH 7.0). KHN analysis was performed with a microhardness tester under a
      load of 25 gf for 5 seconds. The average SR was obtained with a rugosimeter. KHN
      and SR were analyzed before and after treatments. For morphological analysis,
      specimens were dehydrated and gold-sputtered, and scanning electron micrographs
      were obtained and analyzed by 3 examiners with a double-blinded technique. KHN
      and SR results were analyzed by one-way ANOVA and Tukey's test (p < 0.05).
      RESULTS: Only the Low NaF/Acidic and Low NaF/Neutral groups showed significant
      differences between the initial and final KHN values. All bleached groups
      presented significant differences between the initial and final SR values. Among
      the bleached groups, the least and most morphological changes were shown by the
      High NaF/Neutral and the Low NaF/Acidic group, respectively. CONCLUSION:
      Treatment with 35% HP and 2% NaF at pH 7.0 promoted the least changes in
      morphology, hardness and roughness among the bleached groups. CLINICAL
      SIGNIFICANCE: In-office bleaching with high-concentration HP and 2% NaF at
      neutral pH promoted the least changes in enamel hardness, SR, and morphology
      compared to other treatments.

PMID- 25576102
TI  - Evaluation of mental foramen position from panoramic dental radiographs.
AB  - OBJECTIVE: Evaluate the position of mental foramen by measuring the vertical bone
      height from digital panoramic radiograph and also the variation of resorption
      pattern by gender and extraction time frame. Materials and methods/study design:
      Digital panoramic radiographs of 500 patients were reviewed. The study population
      was divided into four age groups aged 30 to 70 years as (30-39, 40-49, 50-59 and
      60-70 years of age). Radiographic Position of mental foramen was evaluated in
      each panoramic radiograph by measuring the distance from the marginal bone to the
      mental foramen was being measured. Measurements were taken in each radiograph
      using Clini-view software. The data collected was subjected to statistical
      analysis using paired students t-test and chi-square tests. RESULTS AND
      CONCLUSION: In our study it was noted that the vertical measurements calculated
      from the superior margin of mental foramen to the crest of alveolar ridge were
      greater in edentulous men than in women. This measurement decreased significantly
      with age. We have noted here that resorption pattern between males and females
      can be used as an early diagnostic tool and for implant analysis. Studies
      comparing right and left side edentulous mandibular region are needed for further
      confirmation.

PMID- 25576103
TI  - Comparison of nickel and chromium ions released from stainless steel and NiTi
      wires after immersion in Oral B(r), Orthokin(r) and artificial saliva.
AB  - AIM: Oral environment of the mouth is a suitable place for biodegradation of
      alloys used in orthodontic wires. The toxicity of these alloys namely nickel and
      chromium has concerned the researchers about the release of these ions from
      orthodontic wires and brackets. The aim of this study was to measure the levels
      of nickel and chromium ions released from 0.018" stainless steel (SS) and NiTi
      wires after immersion in three solutions. MATERIALS AND METHODS: One hundred and
      forty-four round NiTi and 144 round SS archwires with the diameters of 0.018"
      were immersed in Oral B(r), Orthokin(r) and artificial saliva. The amounts of
      nickel and chromium ions released were measured after 1, 6, 24 hours and 7 days.
      RESULTS: Two way repeated ANOVA showed that the amount of chromium and nickel
      significantly increased in all solutions during all time intervals (p < 0.002).
      CONCLUSION: Chromium and nickel ions were released more in NiTi wire in all
      solutions compared with SS wire. The lowest increase rate was also seen in
      artificial saliva. CLINICAL SIGNIFICANCE: There is general consensus in
      literature that even very little amounts of nickel and chromium are dangerous for
      human body specially when absorbed orally; therefore, knowing the precise amount
      of these ions released from different wires when immersed in different
      mouthwashes is of high priority.

PMID- 25576105
TI  - Resistance of teeth with simulated incomplete rhizogenesis with intraradicular
      post or root canal filling.
AB  - AIM: The aim of this study was to evaluate the fracture strength (FS) of bovine
      incisors with simulated incomplete rhizogenesis (IR) after different
      intraradicular treatments. MATERIALS AND METHODS: Incomplete rhizogenesis was
      simulated by sectioning the crowns and roots of 40 bovine incisors. Root canal
      preparation was performed and the samples divided into 4 groups (n = 10): GI
      negative control with intra-radicular preparation; GII-positive control without
      intra-radicular preparation; GIII-glass fiber post cemented with resin cement and
      GIV-root canal obturation with Epiphany/Resilon system. In GIII and GIV, 4.0 mm
      apical plugs of mineral trioxide aggregate (MTA) were done. The samples were
      embedded into cylinders with polystyrene resin, and the periodontal ligament was
      simulated with a medium-viscosity polyether-based impression material (Impregum
      Soft). The specimens were submitted to compressive fracture strength test (0.5
      mm/min at 135 degrees  in relation to the long axis of the tooth) in a mechanical
      testing machine MTS 810. Data were submitted to ANOVA and Tukey's test (alpha =
      0.05). RESULTS: GIII produced the highest FS values (p < 0.05). GI and GIV showed
      similar FS results (p > 0.05) but smaller than GII (p < 0.05). CONCLUSION: Glass
      fiber intraradicular posts provided the FS increase of teeth with simulated
      incomplete rhizogenesis. Epiphany/Resilon root canal flling with MTA plug did not
      provide the increase of the fracture strength to teeth with simulated incomplete
      rhizogenesis. CLINICAL SIGNIFICANCE: The fiber post reinforces the root structure
      of teeth with incomplete rhizogenesis.

PMID- 25576104
TI  - Influence of simulated pulpal pressure on efficacy of bleaching gels.
AB  - AIM: The aim of this study was to investigate the Influence of simulated pulpal
      pressure on efficacy of bleaching gels. MATERIALS AND METHODS: Cylindrical enamel
      dentin specimens from bovine teeth (3 mm diameter, enamel and dentin layer each 1
      mm thick) were divided into 4 groups, according to the bleaching treatment:
      negative control (non-bleached), bleached with 10% carbamide peroxide (CP),
      bleached with 7.5% hydrogen peroxide (HP) and bleached with 35% hydrogen
      peroxide. Ten percent CP gel was applied for 8 h/day and 7.5% HP for 1 h/day,
      during 14 days. For 35% HP treatment, two sessions of 45 minutes each were
      employed. In intermediate periods specimens were stored in artificial saliva.
      Experimental groups (n = 19) were subdivided according to the simulation of
      pulpal pressure (25 mm Hg) during bleaching treatment. Initial color measurement
      and after bleaching treatment were assessed by spectrophotometry, using CIE
      L*a*b* system. The data were statistically analyzed by ANOVA and Dunnett's post
      hoc tests (p < 0.05). RESULTS: There was significant difference of DeltaE for all
      experimental groups compared to negative control group, according to Dunnett's
      test (p < 0.0001). There were no significant difference for total color variation
      (DeltaE) among experimental groups (p > 0.05). CONCLUSION: It was concluded that
      all bleaching gels showed bleaching efficacy compared to non-bleached group and
      that the simulated pulpal pressure did not Influence the bleaching outcomes of
      the tested gels. CLINICAL SIGNIFICANCE: Although numerous in vitro studies
      investigating the efficacy of bleaching agents have been performed, they do not
      properly simulate the pulpal pressure. In order to make these studies closer to
      clinical conditions, it is important to reproduce these conditions in laboratory,
      so the results can be more reliable. This in vitro study was performed under
      simulated pulpal pressure, aiming to investigate its Influence on dental
      bleaching outcomes.

PMID- 25576106
TI  - Clinical and radiographic evaluation of narrow-diameter titanium-zirconium
      implants in unilateral atrophic mandibular distal extensions: a 1-year pilot
      study.
AB  - BACKGROUND: The use of endosseous dental implants has led to more sophisticated
      fxed options when considering treatment of patients with distal extensions. The
      use of narrow-diameter implants may reduce the necessity for bone augmentation.
      The mechanical strength of titanium is limited, so titanium alloys with greater
      tensile and fatigue strength may be preferable. PURPOSE: The purpose of this
      study was to evaluate clinically and radiographically the performance of narrow
      diameter bone level implants made from titanium-zirconium alloy (TiZr,
      Roxolid(TM)) in restoring unilateral atrophic mandibular distal extensions with
      fxed dental prostheses. MATERIALS AND METHODS: Twenty partially edentulous
      patients with unilateral atrophic mandibular distal extensions received two 3.3
      mm diameter bone level TiZr implants (Straumann AG, Basel, Switzerland). The two
      implants were restored with 3-units ceramo-metal fxed partial dentures.
      Standardized clinical and radiographic parameters (survival rate, probing pocket
      depth and marginal bone loss) were evaluated at the time of the completion of the
      prosthetic treatment (baseline) and after 3, 6 and 12 months of functional
      loading. Prosthetic complications were also assessed. RESULTS: The survival rate
      for narrow-diameter bone level TiZr implants was 100% after 1 year of functional
      loading. There were no statistically significant differences between the values
      of probing pocket depth over the follow-up period. All implants showed less than
      1 mm of marginal bone loss at the end of the follow-up period. CONCLUSION: Within
      the limitations of this 1-year pilot study, the use of narrow-diameter bone level
      TiZr implants appears to be predictable in restoring the unilateral atrophic
      mandibular distal extensions. This type of implants meets established success and
      survival criteria after 1 year.

PMID- 25576107
TI  - Apical extrusion of debris and irrigant using novel preparation systems.
AB  - AIM: The aim of this in vitro study was to assess the amount of apically extruded
      debris and irrigant using Reciproc vs self-adjusting fle (SAF) and to investigate
      the effect, if any, of gravitational force via mandibular and maxillary
      positioning of the teeth. MATERIALS AND METHODS: Forty human mandibular premolars
      were randomly assigned to four groups of 10 teeth each. The root canals were
      instrumented according to the manufacturers' instructions using the Reciproc and
      SAF. Sodium hypochlorite was used as the irrigant. The apically extruded debris
      was collected in pre-weighted glass vials using the Myers and Montgomery method,
      and teeth were placed in vials both in downward and upward positions. After
      drying, the mean weight of debris was assessed with a microbalance and
      statistically analyzed using two-way ANOVA with Bonferroni correction. RESULTS:
      All instrumentation techniques and positions caused measurable apical extrusion
      of debris. A significant difference was observed according to position and
      instrument used (p < 0.05). The Reciproc extruded significantly more debris than
      SAF and vial downward position extruded significantly more debris than upward
      position (p < 0.05). CONCLUSION: Under the conditions of this study, all systems
      caused apical debris extrusion, especially in the downward position. CLINICAL
      SIGNIFICANCE: According to results of this study, the SAF was associated with
      less debris extrusion compared to the Reciproc in both mandibular and maxillary
      positions.

PMID- 25576108
TI  - Comparison of internal fit between implant abutments and cast metal crowns vs
      laser-sintered crowns.
AB  - AIM: A common problem related to cemented single crowns is the internal misfit,
      which may cause inadequate retention, especially when seated on the implant
      abutment. The aim of this study was to compare the internal fit of Co-Cr crowns
      using a traditional lost-wax casting technique from laser-sintered Co-Cr alloy
      crowns. MATERIALS AND METHODS: Twelve metallic crowns per each technique were
      fabricated. The effect of the thickness of cement, originated internal gap was
      evaluated. Crowns were cemented on the implant abutments with resin cement, and
      the internal fit of crowns was measured at five areas with an optical microscope.
      The data were analyzed, and the means were compared with a t-test (p<0.05).
      RESULTS: The internal gap width measurements for the laser-sintered group (min.
      52.19 +/- 11.61 MUm and max. 140.01 +/- 31.84 MUm) indicated the presence of a
      significantly closed internal gap compared to the crowns obtained through the
      lost wax method (min. 65.50 +/- 9.54 MUm and max. 313.46 +/- 48.12 MUm).
      CONCLUSION: The fit of the metal crown likely varies with the fabrication
      technique. The use of techniques that enable the adjustment of crown parameters,
      such as the laser sintering technique, maintains the desired fit between casting
      and implant abutments. CLINICAL SIGNIFICANCE: This study investigated which
      technique affects the internal fit of cemented implant-supported crowns,
      comparing the use of lost wax casting and laser-sintered metal dental alloys. The
      results of this study indicate that the use of laser-sintered crowns can improve
      for crown accuracy.

PMID- 25576109
TI  - Scanning electron microscopic analysis to compare the cleaning efficiency of
      three different irrigation systems at different root canal levels: an in vitro
      study.
AB  - AIM: This study compared the efficacy of conventional, endovac and ultrasonic
      irrigation system for the removal of debris from root canal walls, using scanning
      electron microscopy (SEM) at cervical, middle and apical 3rd. MATERIALS AND
      METHODS: A total of 30 freshly extracted human mandibular premolars with complete
      root formation were selected and divided into group 1 endovac, group 2
      conventional and group 3 ultrasonic. After instrumentation and irrigation, the
      teeth were sectioned in buccolingual direction and analyzed by SEM and the
      results were analyzed statistically by students unpaired 't' test. RESULTS: There
      was significant difference between mean values of cervical (CV), middle (M), and
      apical (A) when endovac compared with conventional and conventional compared with
      ultrasonic group (i.e. < 0.05) and no significant difference between mean values
      at CV, M and A when endovac compared with ultrasonic group. CONCLUSION: Among all
      groups ultrasonic and endovac group showed cleaner canal walls and less amount of
      debris than conventional group. CLINICAL SIGNIFICANCE: Application of ultrasonic
      and endovac can be used effectively for irrigation of canals leading to least
      debris and better prognosis.

PMID- 25576110
TI  - Evaluation of the effect of a home bleaching agent on surface characteristics of
      indirect esthetic restorative materials--part II microhardness.
AB  - BACKGROUND: The exponential usage of esthetic restorative materials is beholden
      to society needs and desires. Interaction between the bleaching agents and the
      esthetic restorative materials is of critical importance. AIM: This in vitro
      study has been conducted to evaluate the effect of a home bleaching agent,
      carbamide peroxide (CP) 38%, on the microhardness of the fiber reinforced
      composite (FRC), overglazed, autoglazed, or polished porcelain specimens.
      MATERIALS AND METHODS: For overglazed, autoglazed, polished ceramics and also FRC
      cylindrical specimens (n = 20 per group) were prepared. The specimens were stored
      in distilled water at 37 degrees C for 48 hours prior to testing. Six samples
      from each group were selected randomly as negative controls which were stored in
      distilled water at 37 degrees C that was changed daily. CP 38% was applied on the
      test specimens for 15 minutes, twice a day for 14 days. By using Knoop
      microhardness tester microhardness testing for baseline, control and test
      specimens was conducted. Data were statistically analyzed using paired t-test,
      Mann-Whitney test, and Kruskal-Wallis test. RESULTS: Home bleaching significantly
      decreased the surface microhardness of all the test samples (p < 0.05), whereas
      the control groups did not show statistically significant changes after 2 weeks.
      The polished porcelain and polished composite specimens showed the most
      significant change in microhard-ness after bleaching process (p < 0.05).
      CONCLUSION: Although the type of surface preparation affects the susceptibility
      of the porcelain surface to the bleaching agent, no special preparation can
      preclude such adverse effects. CLINICAL SIGNIFICANCE: The contact of home
      bleaching agents with esthetic restorative materials is unavoidable. Therefore
      protecting these restorations from bleaching agents and reglazing or at least
      polishing the restorations after bleaching is recommended.

PMID- 25576111
TI  - Influence of fiber post cementation length on coronal microleakage values in
      vitro and finite element analysis.
AB  - AIM: This study aims to evaluate, the Influence of different fiber posts
      cementation lengths by finite element analysis (FEA) and coronal microleakage.
      MATERIALS AND METHODS: Fifty anterior bovine teeth were sectioned to obtain roots
      with 16 mm length. The coronal length of the post was 6 mm for all groups, while
      the radicular length were varied 6, 8, 10 or 12 mm. The fiber posts surfaces were
      cleaned with alcohol and silanized. Then the posts were cemented using a two
      steps total etch-and-rinse adhesive system + conventional resin cement. Forty
      teeth were submitted to mechanical cycling (45 degrees ; 2.000.000 cycles; 90N;
      4Hz; 37 degrees C) and ten teeth with radicular length of 12 mm was not
      submitted, ser ving as c ontrol. So, the experimental design was composed by
      different ratios of post coronal length/post radicular length and mechanical
      cycling (MC): Gr1- 1/1 + MC; Gr2- 3/4 + MC; Gr3- 3/5 + MC; Gr4- 1/2 + MC. All
      groups were immersed in a 1% toluidine blue solution. After 24 hours, the teeth
      were longitudinally sectioned and the microleakage scores was given by a blind
      operator. Data were submitted to Kruskal-Wallis test (p = 0.05). The experimental
      variables were simulated in two-dimensional finite element analysis (2D-FEA). The
      maximum principal stress distributions were compared. RESULTS: No difference was
      observed in microleakage values between the cycled groups, whilst the control
      groups showed the lowest values. FEA analysis showed similar maximum principal
      stress distribution between the groups. CONCLUSION: Mechanical cycling affected
      the values of coronal microleakage and different cementation length generated
      similar values of coronal microleakage and stress distribution. CLINICAL
      SIGNIFICANCE: These results showed that from the microleakage point of view, more
      conservative cementation lengths have the same effect as longer cementation
      lengths.

PMID- 25576112
TI  - The influence of different angles and reciprocation on the shaping ability of two
      nickel-titanium rotary root canal instruments.
AB  - PURPOSE: The purpose of the present study was to investigate and compare the
      effect of different reciprocating movements and angles on the shaping ability of
      the WaveOne and the single-fle ProTaper F2 using cone beam computed tomography
      (CBCT). MATERIALS AND METHODS: The mesiobuccal canals of 40 extracted maxillary
      molars, with curvatures of 20 to 45 degrees  were coded and randomly divided into
      4 equal experimental groups according to the instrument used (ProTaper F2 fle and
      Wa-veOne) and the reciprocation range, for both instruments, a 150 degrees  angle
      was used for cutting and a 30 degrees  angle was used for release. Group 1 -
      WaveOne primary 150 degrees  CCW rotation angle and 30 degrees  CW rotation
      angle; Group 2 - WaveOne 90 degrees  CCW rotation angle and 30 degrees  CW
      rotation angle; Group 3 - ProTaper F2 150 degrees  CW rotation angle and 30
      degrees  CCW rotation angle; Group 4 - ProTaper F2 90 degrees  CW rotation angle
      and 30 degrees  CCW rotation angle. Canals were scanned before and after
      preparation using CBCT to evaluate the volumetric change, canal transportation
      and the canal centering ability at 2.6, 5.2 and 7.8 mm from the apex. The mean +/
      standard deviation (SD) values were analyzed, and the significance level was set
      at p <= 0.05. RESULTS: There was no significant difference in the amount of
      dentin removed among the experimental groups, except that WaveOne 150 degrees CCW
      30 degrees CW significantly showed the least volume of dentin removed (0.40 +/-
      0.9) at 7.8 mm. All rotary systems tested in the different groups resulted in
      canal transportation in different directions at all examined levels. WaveOne 150
      degrees CCW 30 degrees CW, demonstrated the lowest mean value of root canal
      transportation in both the mesial and furcal directions and in both the coronal
      and apical directions compared to the other groups. At the 7.8 level, WaveOne 150
      degrees CCW 30 degrees CW yielded the highest mean centering ratio, whereas
      ProTaper F2 CW 150 degrees  CCW 30 degrees  yielded the lowest, statistically
      significant at p <= 0.05. CONCLUSION: The results of the present study
      demonstrated that differences among various reciprocating motions and angles
      could affect the shaping ability of a single-fle Nickel-titanium (NiTi)
      instrument.

PMID- 25576113
TI  - The prestretching effect on the force decay of orthodontic elastic chain.
AB  - This in vitro study evaluated the Influence of prestretching, in the force decay
      of orthodontic elastic chains, at three time intervals: 2, 7 and 30 days with the
      brands Morelli, Orthometric and American Orthodontics. In the experimental group,
      prestretching was performed, stretching the elastics to increase them by 50% of
      their original length three times in a quick and sequential mode. All of the
      elastic chains were kept stretched and stored in artificial saliva at 37 degrees
      C until the time of force measurement. For comparisons between the control and
      experimental groups, the Mann-Whitney test was used. For comparisons between time
      points and brands, the Kruskal-Wallis test was used, and for multiple
      comparisons, Miller's post-hoc test was used. The results showed statistically
      significant differences among the different commercial brands tested at the
      initial time point. The mean force at the initial time point ranged from 2.57 to
      3.17 N. By day 2, the force values were between 0.97 and 1.49 N; by day 7, the
      values were 0.56 and 0.94 N. By day 30, the force values ranged between 0.27 and
      0.66 N. We concluded that performing and duration of prestretching and the brand
      all Influenced the force decay of orthodontic elastic chains. Time had a greater
      Influence on the decay of the elastics than brand or prestretching.

PMID- 25576114
TI  - The comparison of mandibular radiomorphometric indices in panoramic radiography
      between patients with chronic periodontitis and healthy individuals.
AB  - AIM: Osteoporosis and periodontitis are two separate diseases with different
      origins and manifestations. It is believed that these diseases linked together,
      because they both lead to bone damage, some risk factors are similar, they both
      have the highest prevalence in middle-aged and older women. Some studies showed
      that the use of panoramic radiography and special indices could be reliable tools
      for osteoporosis screening. This study was performed to evaluate the relationship
      between periodontal disease and jaw osteoporotic indices. MATERIALS AND METHODS:
      Eighty-two patients with chronic periodontitis and 80 healthy individuals were
      selected, they had been referred to a private oral and maxillofacial radiology
      clinic to take a panoramic radiograph. Then panoramic indicators; including the
      mandibular cortical index (MCI), mental index (MI), and panoramic mandible index
      (PMI) in both groups were measured, recorded and analyzed. RESULTS: The mean age
      of investigated individuals was 39/8 +/- 9/33. 58.6% of participants were females
      and 41.4% were males. MI and PMI levels in the periodontal group were more than
      the periodontally healthy group, but the differences between the two groups was
      not statistically significant (p = 0.808 and p = 0.102 respectively). The MCI
      level was significantly different between two groups (p = 0.028). CONCLUSION: The
      results of this study showed that there is significant relationship between MCI
      in panoramic radiography and chronic periodontitis. It is suggested to perform
      more studies to confrm if this index could be used for screening and indicating
      of bone status in high risk individuals. This study did not show a strong
      evidence of a relationship between osteoporosis and periodontitis. CLINICAL
      SIGNIFICANCE: Since panoramic radiographs are routinely used for screening in
      dental practice, any association between radiomorphometric indices of mandible in
      periodontitis patients might be useful in prediction of osteoporosis in patients
      referring to dental clinics.

PMID- 25576115
TI  - Clinicopathologic evaluation of lesions associated with tobacco usage.
AB  - INTRODUCTION: Tobacco usage in different forms is the single most common
      etiological factor responsible for oral cancers. The aim of the present study was
      to record various mucosal lesions associated with tobacco usage and to ascertain
      the prevalence of dysplasia in them by histopathological evaluation and to
      compare the extent of dysplastic features seen among patients associated with a
      habit of smoked and smokeless form of tobacco. MATERIALS AND METHODS: Seventy-six
      patients with the clinical diagnosis of tobacco related lesions (Leukoplakia,
      Erythroplakia, Nicotina stomatitis, Tobacco pouch keratosis) were selected. A
      detailed description of the clinical presentation of the lesion was noted and the
      patients were subjected to incisional biopsy followed by a histopathological
      evaluation. RESULTS: Showed dysplastic changes in 50 cases (65.8%) ranging from
      mild dysplasia in 27 cases (35.5%), moderate dysplasia in 17 cases (22.4%) and 6
      cases (7.9%) showed severe dysplasia. Moderate to severe dysplasia was 1.83 times
      more likely to occur with smokeless tobacco usage when compared to smoked form.
      Data obtained from this study reveals that patients with a duration of tobacco
      usage more than 10 years were 2.17 times more likely to have moderate to severe
      dysplasia (p = 0.154). CONCLUSION: Thus, the study highlights the role of oral
      physicians in detecting oral mucosal lesions and screening high-risk patients on
      a regular basis and also reaffrms the importance of public education, stressing
      the risk factors for oral cancers.

PMID- 25576116
TI  - An in vitro evaluation of the cytotoxicity of varying concentrations of sodium
      hypochlorite on human mesenchymal stem cells.
AB  - AIM: To evaluate and compare the cytotoxicity of various concentrations of sodium
      hypochlorite on immortalized human bone marrow mesenchymal stem cells (MSCs).
      MATERIALS AND METHODS: The 5.25 percent sodium hypochlo-rite (NaOCl) at
      concentrations of 0.5, 0.1, 0.025, 0.0125, and 0.005 mg/ml were used to assess
      the cytotoxic effect on MSCs. Immortalized human bone marrow mesenchymal stem
      cells (hTERT-MSCs) were exposed to NaOCl at 5 different concentrations. Cell
      viability was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) and alamarBlue assays. The cell morphology changes were assessed
      with scanning electron microscopy (SEM) after exposure to 2, 4, and 24 hour
      incubation. The ethidium bromide/acridine orange (EB/ AO) fuorescent stain was
      applied to the cells in the 8-chamber slides after they were incubated with the
      testing agents for 2 and 4 hours to detect live and dead cells. The observations
      were quantitatively and qualitatively analyzed. RESULTS: The cell viability study
      using MTT assay and AB assay showed significant reduction with varying
      concentration at 2 and 4 hours incubation period. The cell viability decreased
      with the higher percentage of NaOCl. The exposure time also revealed an inverse
      relation to the cell viability. The SEM analysis showed reduction in the number
      of cells and morphological alterations with 0.5 mg/ml at 2 and 4 hours compared
      to 0.025 mg/ml NaOCl. Destruction of the cells with structural alterations and
      lysis was evident under fuorescence microscope when the cells were exposed to 0.5
      mg/ml NaOCl. CONCLUSION: Within the limitations of this in vitro study it can be
      concluded that NaOCl is toxic to the human bone marrow MSCs. The cell lysis was
      evident with higher concentration of sodium hypochlorite. From the observations,
      it can be concluded that a lower concentration of NaOCl may be used as endodontic
      irrigant due to its cytotoxic properties. Further studies are mandatory to evolve
      a consensus on the optimal concentration of sodium hypochlorite to be used as
      endodontic irrigant.

PMID- 25576117
TI  - Oral health-related quality of life and periodontal and dental health status in
      Iranian hemodialysis patients.
AB  - AIM: The aim of this study was to evaluate oral health status and oral health
      related quality of life (OHRQoL) in Iranian patients undergoing hemodialysis.
      MATERIALS AND METHODS: In this cross-sectional study 145 (95 dentate and 50
      edentulous) patients undergoing hemodialysis participated. Demographic
      information, laboratory findings and dental health status was recorded by a
      standard form. Oral hygiene status was obtained by simplifed oral hygiene index
      (OHI-S) and oral health was evaluated by decay missing flling teeth (DMFT) index,
      plaque index (PLI) and periodontal disease index. Oral health related quality of
      life was determined by means of short form oral health impact profle (OHIP-14)
      and general oral health assessment index (GOHAI). RESULTS: The mean (+/- SD)
      DMFT, PLI and PDI were 15.47 +/- 7.85, 2.03 +/- 0.95, 4.09 +/- 1.31 respectively.
      OHI-S was good in 7 (7.4%), fair 25 (26.6%) and poor in 38 (26.6%) of patients.
      The mean OHIP-14 and GOHAI scores were 31.32 +/- 12.53 and 29.07 +/- 8.5
      respectively. The self-perceived oral health of 58 (40%) was good, 49(33.8%) was
      fair and 38 (26.2%) was poor. Patients with higher scores for the questionnaires
      had significantly worst self-rated oral health. Besides, there was a significant
      positive correlation between dental and periodontal variables with OHIP-14 and
      GOHAI scores. CONCLUSION: Hemodialysis patients had a poor oral hygiene and
      periodontal status, weak attitudes and negligence toward oral health but they
      were satisfed of their oral health condition and their OHRQoL was approximately
      good. Therefor it should be communications between nephrologists and oral health
      care professionals for promoting the oral health status of the patients. CLINICAL
      SIGNIFICANCE: The findings high light the need of comprehensive oral examinations
      including periodontal therapy, restorative treatment, preventive dental treatment
      and follow-up care in the hemodialysis patients.

PMID- 25576118
TI  - Orthodontic management of a patient with cerebral palsy: six years follow-up.
AB  - AIM: Cerebral palsy (CP) is a disorder that affects muscle tone, movement and
      motor skills. CP can also lead to other health issues, including vision, hearing
      and speech problems, as well as learning disabilities and dental problems. A case
      report describing the successful orthodontic treatment of a 10-year-old boy with
      the dyskinesia type of CP and severe malocclusion is presented. MATERIALS AND
      METHODS: A 10-year and 2-month old boy was presented by his parents for
      orthodontic treatment, complaining of his unsatisfactory occlusion and poor
      chewing efficacy. An extraoral examination showed a convex profle. An intraoral
      examination showed the patient to be in mixed dentition with a class II molar
      relationship, 10 mm overjet and 4 mm overbite. In addition, his maxillary and
      mandibular arches were severely crowded. Cephalometric analysis indicated a
      severe skeletal class II discrepancy, which was confrmed by an ANB of 12 degrees
      . The frst phase of treatment involved the use of twin blocks with a headgear
      tube to attempt some growth modification and reduce the overjet. Once it was
      clear that the appliance was being well tolerated and the oral hygiene was
      satisfactory, the fxed appliance was used. RESULTS: Because of the good
      participation of the patient and his parents, orthodontic treatment was
      successful in the patient, achieving a normal overjet in combination with
      successful orofacial therapy. CONCLUSION: As demonstrated in our case report, the
      success of the treatment was dependent on the cooperation of the patient and his
      parents. Furthermore, this case illustrates the importance of the treatment by a
      dental team in patients with CP.

PMID- 25576119
TI  - The radix entomolaris and radix paramolaris: an endodontic challenge.
AB  - Success of endodontic treatment depends on the proper identi-fication of all the
      canals, thorough chemomechanical preparation followed by three-dimensional
      obturation with hermetic seal. Failure of any of these steps may occur due to
      unusual tooth morphology. Usually mandibular molars have two roots with three
      canals but in few teeth, the number of roots and canals vary. The variation in
      the number of roots, if extra root located lingually called radix entomolaris
      (RE) or located bucally called radix paramolaris (RP). This article presents
      successful endo-dontic treatment of two mandibular frst molars with extra roots
      one is with radix entomolaris and other is with radix paramolaris, both of which
      are rare microstructures.

PMID- 25576120
TI  - Complete ossification of the stylohyoid chain as cause of Eagle's syndrome: a
      very rare case report.
AB  - AIM: To report on a patient with Eagle's syndrome with a complete and very large
      ossification of the stylohyoid complex on the right side that to our best
      knowledge has never been published previously. BACKGROUND: Eagle's syndrome is
      characterized by a set of symptoms that are caused by the irritation of the
      neurovascular and soft-tissues caused by an elongated styloid process or
      ossification of stylohyoid ligament. CASE DESCRIPTION: Because of the high
      discomfort and pain degree as well as limitations of mandibular and head mobility
      and also the thickness of the ossifed stylohyoid chain, the patient was treated
      surgically by removing the hypertrophic segment. CONCLUSION: These symptoms
      subsided completely after the surgical excision of the anomaly. The elongated
      styloid process on the left side was symptom free. CLINICAL SIGNIFICANCE: Eagle's
      syndrome symptoms are not specific and can mimic those of other disorders, the
      syndrome must be included in the differential diagnosis of patients with pain in
      the orofacial, pharyngeal and cervical area.

PMID- 25576121
TI  - An esthetics rehabilitation with computer-aided design/ computer-aided
      manufacturing technology.
AB  - AIM: This paper describes a case of a rehabilitation involving Computer Aided
      Design/Computer Aided Manufacturing (CAD-CAM) system in implant supported and
      dental supported prostheses using zirconia as framework. BACKGROUND: The CAD-CAM
      technology has developed considerably over last few years, becoming a reality in
      dental practice. Among the widely used systems are the systems based on zirconia
      which demonstrate important physical and mechanical properties of high strength,
      adequate fracture toughness, biocompatibility and esthetics, and are indicated
      for unitary prosthetic restorations and posterior and anterior framework. CASE
      DESCRIPTION: All the modeling was performed by using CAD-CAM system and
      prostheses were cemented using resin cement best suited for each situation.
      CONCLUSION: The rehabilitation of the maxillary arch using zirconia framework
      demonstrated satisfactory esthetic and functional results after a 12-month
      control and revealed no biological and technical complications. CLINICAL
      SIGNIFICANCE: This article shows the important of use technology CAD/CAM in the
      manufacture of dental prosthesis and implant-supported.

PMID- 25576122
TI  - Atraumatic extraction, implant placement and immediate provisionalization.
AB  - Front tooth extraction typically results in significant loss of hard and soft
      tissue volume, both in the vestibular-lingual and mesiodistal directions. As
      these changes can compromise the esthetic results of prosthetic rehabilitation,
      extraction techniques that cause minimal trauma to the remnant tissues are
      applied in combination with immediate implant placement to minimize such
      alterations. The case reported in the present article illustrates a therapeutic
      plan consisting of atraumatic extraction followed by immediate implant placement
      and provisionalization. When carefully indicated and planned, our results
      indicate that this technique may provide promising immediate results relative to
      the maintenance and stability of the peri-implanted tissues.

PMID- 25576123
TI  - Aggressive periodontitis in a Nigerian teaching hospital.
AB  - AIM: These case series were aimed at highlighting late presentations of
      aggressive periodontitis (AP) in a teaching hospital as well as proffering
      possible reasons for such presentations which would serve as part of the solution
      to prevent such presentations in the future. BACKGROUND: Aggressive periodontitis
      is a severe form of destructive periodontitis traditionally believed to present
      around puberty. However, many cases seen in a teaching hospital presented much
      later for yet-to-be explained reasons. CASE DESCRIPTION: Seven patients referred
      to the specialist periodontal clinic of a Nigerian teaching hospital presented
      with clinical features consistent with AP. Most of the patients were over twenty
      and some over thirty years of age. CONCLUSION: Aggressive periodontitis patients
      seen in our center were often outside the traditional age brackets. The range of
      treatment options available to the patients were under-utilized due to serious
      financial constraints. CLINICAL SIGNIFICANCE: Aggressive periodontitis comes with
      serious psychological challenges and severe morbidity. Prompt diagnosis and
      effective management hold the key to success It is important to investigate why
      many of the cases seen in our center presented that late. Could be due to
      ignorance and poverty or could be due to failure of dentists recognize these
      cases and consequent misdiagnosis? Further studies are needed to answer these
      questions.

PMID- 25576124
TI  - The ambiguous salivary myoepithelial cells.
AB  - Salivary gland neoplasms present with a diverse histological pattern which is
      mainly because of the presence of specialized myoepithelial cells (MECs). These
      are contractile epithelial cells with smooth muscle like properties. They have
      been also noticed in mammary glands, lacrimal glands, prostate gland, and the
      sweat glands and have varied functions. MECs play an important role in the
      histogenesis of many salivary gland tumors. Knowledge of MECs leads to a better
      understanding of the histological diversity of salivary gland neoplasms. This
      article reviews the physiology, histology, identification and role of these cells
      in salivary gland pathology.

PMID- 25576125
TI  - Dental amalgam phase-down.

PMID- 25576126
TI  - Thirty years of psychosocial research in epilepsy: personal reflections of a
      social scientist.

PMID- 25576127
TI  - Formation of aldehydes and carboxylic acids in ozonated surface water and
      wastewater: a clear relationship with fluorescence changes.
AB  - This study examined the formation of aldehydes and carboxylic acids in ozonated
      surface water and municipal wastewater secondary effluent and addressed
      correlations between the generation of these compounds and concurrent changes of
      the fluorescence of natural/effluent organic matter (NOM/EfOM) substrates.
      Ozonation was effective in removing fluorophores in all excitation/emission
      matrix (EEM) regions, with those operationally assigned to humic- and protein
      like species showing relatively higher reactivity than fulvic-like species.
      Examination of HO exposures and attendant changes of fluorescence-based
      parameters allows establishing strong linear relationships between formation of
      the aldehydes and carboxylic acids and the relative changes of integrated
      fluorescence (DeltaIF/IF0). This demonstrates the feasibility of surrogate
      monitoring of the formation of biodegradable ozonation by-products via online
      measurements of water/wastewater EEM fluorescence. 

PMID- 25576128
TI  - Mineralization of aniline in aqueous solution by electrochemical activation of
      persulfate.
AB  - Oxidative degradation of aniline in aqueous solution was carried out by coupling
      electrolysis with persulfate oxidation, in which a synergistic effect occurred.
      Experiments were performed under a batch-wise mode to evaluate the influence of
      various operation parameters on the electrolytic behavior, such as acidity of
      aqueous solution, temperature, electrode potential, persulfate anion
      concentration and nitrogen/oxygen gas dosage. The aniline pollutants could be
      almost entirely mineralized by means of electro-activated persulfate oxidation,
      wherein sulfate radicals were presumed to be principal oxidizing agents. Besides,
      electrogenerated hydrogen peroxide originated from cathodic reduction of oxygen,
      supplied chiefly by anodic oxidation of water, would contribute partially for
      decomposition of aniline. On the whole, the electro-activated persulfate process
      is a very promising method for treatment of aniline in wastewater. 

PMID- 25576129
TI  - Photocatalytic degradation of polycyclic aromatic hydrocarbon benzo[a]pyrene by
      iron oxides and identification of degradation products.
AB  - Photocatalytic decay profiles of polycyclic aromatic hydrocarbon (PAH)
      benzo[a]pyrene (B[a]P) have been investigated on various synthesized iron oxides
      and on soil surfaces under a set of diverse conditions. Samples were analysed
      using the developed HPLC procedure. Results of the present study demonstrate
      fastest photodisintegration of B[a]P on goethite followed by haematite,
      magnetite, akaganeite and maghemite, respectively. The effect of soil pH,
      irradiation wavelength and iron oxide and oxalic acid dose on the degradation of
      B[a]P was evaluated. The studies revealed enhancement in photodegradation in the
      presence of oxalic acid due to the occurrence of fenton like reaction. The
      results showed faster B[a]P degradation under short wavelength UV radiation. Rate
      constants in acidic, neutral and alkaline soils under optimum dissipation
      conditions were 1.11*10(-2), 7.69*10(-3) and 9.97*10(-3) h(-1), respectively. The
      study indicates that iron oxides along with oxalic acid are effective
      photocatalyst for the remediation of benzo[a]pyrene contaminated soil surfaces.
      The degradation products of B[a]P in the soils of different pH in presence of
      goethite were identified and degradation pathways proposed. Peaks due to toxic
      metabolites such as diones, diols and epoxides disappear after 120 h in all the
      three soils.

PMID- 25576130
TI  - Variations in dissolved organic nitrogen concentration in biofilters with
      different media during drinking water treatment.
AB  - Dissolved organic nitrogen (DON) is potential precursor of disinfection
      byproducts (DBPs), especially nitrogenous DBPs. In this study, we investigated
      the impact of biofilters on DON concentration changes in a drinking water plant.
      A small pilot plant was constructed next to a sedimentation tank in a drinking
      water plant and included activated carbon, quartz sand, anthracite, and ceramsite
      biofilters. As the biofilter layer depth increased, the DON concentration first
      decreased and then increased, and the variation in DON concentration differed
      among the biofilters. In the activated carbon biofilter, the DON concentration
      was reduced by the largest amount in the first part of the column and increased
      by the largest amount in the second part of the column. The biomass in the
      activated carbon filter was less than that in the quartz sand filter in the upper
      column. The heterotrophic bacterial proportion among bacterial flora in the
      activated carbon biofilter was the largest, which might be due to the significant
      reduction in DON in the first part of the column. Overall, the results indicate
      that the DON concentration in biofiltered water can be controlled via the
      selection of appropriate biofilter media. We propose that a two-layer biofilter
      with activated carbon in the upper layer and another media type in the lower
      layer could best reduce the DON concentration.

PMID- 25576131
TI  - Soil bioretention protects juvenile salmon and their prey from the toxic impacts
      of urban stormwater runoff.
AB  - Green stormwater infrastructure (GSI), or low impact development, encompasses a
      diverse and expanding portfolio of strategies to reduce the impacts of stormwater
      runoff on natural systems. Benchmarks for GSI success are usually framed in terms
      of hydrology and water chemistry, with reduced flow and loadings of toxic
      chemical contaminants as primary metrics. Despite the central goal of protecting
      aquatic species abundance and diversity, the effectiveness of GSI treatments in
      maintaining diverse assemblages of sensitive aquatic taxa has not been widely
      evaluated. In the present study we characterized the baseline toxicity of
      untreated urban runoff from a highway in Seattle, WA, across six storm events.
      For all storms, first flush runoff was toxic to the daphniid Ceriodaphnia dubia,
      causing up to 100% mortality or impairing reproduction among survivors. We then
      evaluated whether soil media used in bioretention, a conventional GSI method,
      could reduce or eliminate toxicity to juvenile coho salmon (Oncorhynchus kisutch)
      as well as their macroinvertebrate prey, including cultured C. dubia and wild
      collected mayfly nymphs (Baetis spp.). Untreated highway runoff was generally
      lethal to salmon and invertebrates, and this acute mortality was eliminated when
      the runoff was filtered through soil media in bioretention columns. Soil
      treatment also protected against sublethal reproductive toxicity in C. dubia.
      Thus, a relatively inexpensive GSI technology can be highly effective at
      reversing the acutely lethal and sublethal effects of urban runoff on multiple
      aquatic species. 

PMID- 25576132
TI  - Coke industry and steel metallurgy as the source of soil contamination by
      technogenic magnetic particles, heavy metals and polycyclic aromatic
      hydrocarbons.
AB  - Application of integrated magnetic, geochemical and mineralogical methods for
      qualitative and quantitative assessment of forest topsoils exposed to the
      industrial emissions was the objective of this manuscript. Volume magnetic
      susceptibility (kappa) in three areas of southern Poland close to the coke and
      metallurgical plants was measured directly in the field. Representative topsoil
      samples were collected for further chemical and mineralogical analyses. Topsoil
      magnetic susceptibility in the studied areas depended mainly on the content of
      technogenic magnetic particles (TMPs) and decreased downwind at increasing
      distance from the emitters. In the vicinity of coking plants a high amount of
      polycyclic aromatic hydrocarbons (PAHs) was observed, especially the most
      carcinogenic ones with four- and five-member rings. No significant concentration
      of TMPs (estimated on the base of kappa values) and heavy metals (HM) was
      observed in area where the coke plant was the only pollution source. In areas
      with both coke and metallurgical industry, higher amounts of TMPs, PAHs and HM
      were detected. Morphological and mineralogical analyses of TMPs separated from
      contaminated soil samples revealed their high heterogeneity in respect of
      morphology, grain size, mineral and chemical constitution. Pollution load index
      and toxicity equivalent concentration of PAHs used for soil quality assessment
      indicated its high level of pollution. 

PMID- 25576133
TI  - Bacterial ability in AsIII oxidation and AsV reduction: Relation to arsenic
      tolerance, P uptake, and siderophore production.
AB  - The relationship between bacterial ability in arsenic transformation, siderophore
      production, and P uptake was investigated using six arsenic-resistant bacteria
      isolated from the rhizosphere of arsenic-hyperaccumulator Pteris vittata.
      Bacterial strains of PG5 and 12 were better arsenite (AsIII) oxidizers (31-46 vs.
      6.2-21% of 1 mM AsIII) whereas PG 6, 9, 10 and 16 were better arsenate (AsV)
      reducers (58-95 vs. 7.5-46% of 1 mM AsV). Increase in AsV concentration from 0 to
      1 mM induced 3.0-8.4 times more P uptake by bacteria but increase in P
      concentration from 0.1 to 1 mM reduced AsV uptake by 17-71%, indicating that P
      and AsV were taken up by P transporters. Bacteria producing more siderophores
      (PG5 and 12; >73 MUM equiv) showed greater AsIII oxidation and AsIII resistance
      than those producing less siderophore (PG 6, 9, 10 and 16; <23 MUM equiv). This
      observation was further supported by results obtained from mutants of Pseudomonas
      fluorescens impaired in siderophore production, as they were 23-25% less tolerant
      to AsIII than the wild-type. Arsenic-resistant bacteria increased their arsenic
      tolerance by retaining less arsenic in cells via efficient AsIII oxidation and
      AsV reduction, which were impacted by P uptake and siderophore production.

PMID- 25576134
TI  - Glucocorticoid-induced impairment of long-term memory retrieval in female rats:
      influences of estrous cycle and estrogen.
AB  - Using an inhibitory avoidance (IA) task, the effects of glucocorticoids on memory
      retrieval in intact and ovariectomized (OVX) female rats were investigated. Young
      adult female rats were trained in a one trial IA task (1-mA, 3-s footshock). The
      latency to reenter the dark compartment of the apparatus was recorded in the
      retention test performed 48h after training. Pre-retrieval injection of
      corticosterone (CORT, 1, 3, and 10mg/kg) to OVX rats impaired memory retrieval at
      all doses tested. Similar administration of CORT (3mg/kg) in intact female rats
      impaired memory retrieval in the estrus phase (when endogenous plasma levels of
      estrogen are low) but not in the proestrus phase (when endogenous levels of
      estrogen are high). Concurrent administration of CORT (3mg/kg) and 17-beta
      estradiol (15MUg/kg) in both proestrus and estrous phases impaired memory
      retrieval. Our findings indicate that the effects of corticosterone on memory
      retrieval are modulated by the estrous cycle and 17-beta-estradiol. 

PMID- 25576135
TI  - TuCASA questionnaire for assessment of children with obstructive sleep apnea:
      validation.
AB  - OBJECTIVE: The aim of the present study was to validate The Tucson Children's
      Assessment of Sleep Apnea Study (TuCASA) questionnaire for use in the Brazilian
      population. METHODS: Of the total 62 children who participated in the present
      study (27 girls), aged 4 to 11 years, 45 (72.6%) had sleep-disordered breathing
      (SDB) diagnosed by polysomnography, while 17 (27.4%) had no sleep disorders.
      Translation, back-translation, and pretesting were previously performed. The
      final Portuguese-language version of TuCASA was administered to the participants
      from May 2012 to August 2013. The interviewer was blinded to presence or absence
      of SDB. Cronbach's alpha for the overall scale (with 95% CI) and the effect of
      excluding any items were evaluated. RESULTS: There was no difference among TuCASA
      items/score and the presence of SDB with either age or gender. The TuCASA had a
      Cronbach's alpha coefficient of 0.726 (95% CI 0.614 to 0.817), which denotes
      satisfactory internal consistency - a finding reinforced by evaluation of the
      effect of item exclusion on the questionnaire. Convergent validity was also
      satisfactory, in as much as most correlations were positive and significant.
      CONCLUSION: The translated version of the TuCASA questionnaire was validated for
      Brazilian populations and proved to be a reliable, validated instrument that can
      be used in clinical practice for evaluation of children with symptoms of SDB.

PMID- 25576136
TI  - Transcranial direct current stimulation on primary sensorimotor area has no
      effect in patients with drug-naive restless legs syndrome: a proof-of-concept
      clinical trial.
AB  - OBJECTIVE: To evaluate the efficacy of transcranial direct current stimulation
      (tDCS) in people with drug-naive restless legs syndrome (RLS). METHODS: A two
      week, double-blind, randomized, sham-controlled trial was performed. Thirty-three
      females with RLS were recruited. Participants received five sessions of tDCS
      using cathodal, anodal or sham stimulation. They were assessed at baseline (T0),
      three days (T1) and 13 days (T2) after the end of tDCS. Primary outcomes included
      the International RLS Group Rating Scale (IRLS) and the Clinical Global
      Impressions-Improvement (CGI-I). Secondary outcomes included the Patient Global
      Impression scale, the Pittsburgh Sleep Quality Index, the Medical Outcome Study
      sleep subscales, and the Beck Depression Inventory. Objective neurophysiological
      changes were assessed using event-related desynchronization/synchronization
      (ERD/ERS) of electroencephalography. RESULTS: The changes in the IRLS scores, as
      well as the responder rate in the CGI-I scale, did not differ significantly among
      the groups. There was also no significant difference in any of the secondary
      outcome measures and ERD/ERS among the groups. CONCLUSIONS: Transcranial direct
      current stimulation with electrodes on the sensorimotor areas showed no
      significant effect in people with drug-naive RLS.

PMID- 25576137
TI  - Narcolepsy with and without cataplexy, idiopathic hypersomnia with and without
      long sleep time: a cluster analysis.
AB  - BACKGROUND: The successive editions of the International Classification of Sleep
      Disorders (ICSD) reflect the evolution of the concepts of various sleep
      disorders. This is particularly the case for central disorders of
      hypersomnolence, with continuous changes in terminology and divisions of
      narcolepsy, idiopathic hypersomnia, and recurrent hypersomnia. According to the
      ICSD 2nd Edition (ICSD-2), narcolepsy with cataplexy (NwithC), narcolepsy without
      cataplexy (Nw/oC), idiopathic hypersomnia with long sleep time (IHwithLST), and
      idiopathic hypersomnia without long sleep time (IHw/oLST) are four, well-defined
      hypersomnias of central origin. However, in the absence of biological markers,
      doubts have been raised as to the relevance of a division of idiopathic
      hypersomnia into two forms, and it is not yet clear whether Nw/oC and IHw/oLST
      are two distinct entities. With this in mind, it was decided to empirically
      review the ICSD-2 classification by using a hierarchical cluster analysis to see
      whether this division has some relevance, even though the terms "with long sleep
      time" and "without long sleep time" are inappropriate. RESULTS: The cluster
      analysis differentiated three main clusters: Cluster 1, "combined monosymptomatic
      hypersomnia/narcolepsy type 2" (people initially diagnosed with IHw/oLST and
      Nw/oC); Cluster 2 "polysymptomatic hypersomnia" (people initially diagnosed with
      IHwithLST); and Cluster 3, narcolepsy type 1 (people initially diagnosed with
      NwithC). CONCLUSIONS: Cluster analysis confirmed that narcolepsy type 1 and
      polysymptomatic hypersomnia are independent sleep disorders. People who were
      initially diagnosed with Nw/oC and IHw/oLST formed a single cluster, referred to
      as "combined monosymptomatic hypersomnia/narcolepsy type 2."

PMID- 25576138
TI  - Reasons for loss to follow-up of patients with podoconiosis in the Amhara Region,
      northern Ethiopia.
AB  - BACKGROUND: Podoconiosis is a non-infectious form of tropical lymphoedema
      characterised by swelling of the feet and lower legs. Treatment is simple and
      effective yet evidence indicates that a proportion of patients become lost to
      follow-up. METHODS: This study was a quantitative questionnaire-based study which
      aimed to identify the most common reasons for loss to follow-up of patients. A
      total of 191 participants registered with the International Orthodox Christian
      Charities (IOCC) who had become lost to follow-up were included in a cross
      sectional survey based in the Amhara Region, northern Ethiopia. RESULTS: The most
      common reason was distance, stated by 26.7% (51/191). This was significantly
      associated with living further from the treatment site (p=0.02). Having had
      podoconiosis for longer was protective against this (p=0.03). For each additional
      hour of travel time a patient lived from the treatment centre, the odds of them
      reporting 'distance' as the main reason for becoming lost to follow-up increased
      by 1.61 (95% CI: 1.25-2.08). CONCLUSIONS: The consequences of podoconiosis are
      exacerbated by walking long distances, but in most areas, this is currently
      required of patients in order to receive treatment. We recommend expansion of
      services to widen treatment availability, since provision of transport to and
      from treatment centres is unlikely to be feasible.

PMID- 25576139
TI  - Inflammatory colorectal polyps in miniature Dachshunds frequently develop
      ventrally in the colorectal mucosa.
AB  - This study explored the hypothesis that inflammatory colorectal polyps (ICRPs) in
      miniature Dachshunds are more likely to occur ventrally in the colorectum. Angle
      fixed colonoscopic images were collected from 11 miniature Dachshunds with ICRPs
      and randomly rotated. Macroscopic severity at 12 divided angles was scored by
      four veterinarians blinded to the rotation angle. Mean prevalence and severity
      scores of ICRPs were significantly higher ventrally than dorsally (P < 0.01). 

PMID- 25576140
TI  - Limited evidence for trans-generational effects of maternal dietary
      supplementation with omega-3 fatty acids on immunity in broiler chickens.
AB  - The aim of the present study was to investigate whether the immune response of
      broiler chickens is modulated by including different omega-3 (omega-3)
      polyunsaturated fatty acids (PUFAs) in the maternal diet. Broiler breeder hens (n
      = 120 birds per group) were fed one of four diets, differing in the ratios of n
      6:n-3 PUFAs and eicosapentaenoic acid (EPA):docosahexaenoic acid (DHA). At 28
      weeks of age, the eggs produced were incubated to obtain 720 chicks (n = 180 per
      group). All broiler chicks were fed a control diet and were vaccinated against
      Newcastle disease virus (NDV). Blood samples were taken at different time points
      after immunisation with human serum albumin (HuSA) in Freund's adjuvant to
      determine the acute phase response, antibody response and cytokine production.
      Addition of EPA to the maternal diet was associated with greater ovotransferrin
      concentrations post-immunisation, compared to other groups. Altering the ratios
      of n-6:n-3 PUFA or EPA:DHA in the maternal diet did not affect the offspring in
      terms of production of caeruloplasmin, alpha1-acid glycoprotein, interleukin (IL)
      1beta, IL-6, IL-12 or tumour necrosis factor (TNF)-alpha. Dietary manipulation of
      the maternal diet did not influence the specific antibody response to HuSA or
      NDV, nor did it alter the levels of natural antibody binding to keyhole limpet
      haemocyanin in the offspring. Thus, maternal supplementation with n-3 PUFAs
      played a minor role in perinatal programming of the immune response of broiler
      chickens.

PMID- 25576141
TI  - Expression of Toll-like receptor 9 (TLR9) in the lungs and lymphoid tissue of
      pigs.
AB  - The pattern of distribution of Toll-like receptor 9 (TLR9) in different tissues
      varies between species. The aim of the present study was to describe the
      distribution of TLR9 expression in selected tissues and organs of healthy pigs at
      3 weeks and 3 months of age. Representative formalin-fixed samples of lung,
      thymus and secondary lymphoid tissues were evaluated by immunohistochemistry.
      TLR9 positive staining was observed in epithelial cells, vascular endothelium and
      myoepithelial-like cells, as well as in cells of the alveolar septa of the lung.
      Antigen presenting cells of perifollicular zones (interdigitating, macrophage and
      dendritic-like cells) of the Peyer's patches, lymph nodes, spleen and thymus were
      also immunoreactive for TLR9. No differences were seen in TLR9 protein expression
      in tissues from the two age groups.

PMID- 25576142
TI  - The transition from primary to secondary school in mainstream education for
      children with autism spectrum disorder.
AB  - The transition from primary to secondary education (hereafter 'school
      transition') is a major ecological shift that poses considerable social,
      emotional, academic and organisational challenges. It is commonly assumed that
      this school transition is especially difficult for children with autism spectrum
      disorder, but that idea is mainly based on anecdotal evidence and requires
      systematic investigation. We describe change and continuity for children with
      autism spectrum disorder (N = 28, mean age = 11.29 years, mean full-scale IQ =
      87.86) transitioning in mainstream education from primary to secondary school.
      Levels of psychopathology, adaptive functioning and peer victimisation were
      measured by parent, self and teacher report in the last year of primary school,
      and again after one term of secondary school. At follow-up, all participants were
      still in their secondary school, and there was no evidence for a marked
      escalation of difficulties during the transition. Instead, we observed high
      levels of psychopathology and maladaption at baseline which persisted across the
      transition and were in some cases under-recognised. By parent report, levels of
      bullying fell from primary to secondary school. Future research should
      investigate factors, such as school characteristics, that influence the move to
      secondary education in autism spectrum disorder, to inform the development of
      interventions to promote successful school transition. 

PMID- 25576143
TI  - [Surgical therapy for pulmonary metastases from malignant melanoma].
AB  - Results of previous studies question the benefits of pulmonary surgery in
      patients with pulmonary metastases from malignant melanoma. A systematic
      literature search and analysis of articles published since 1 January 2000 was
      carried out to investigate the advantages of metastasectomy and alternative forms
      of therapy. Patients reached a median survival time of 17-40 months and 5-year
      survival rates between 18% and 39.4% after metastasectomy. Intrathoracic
      recurrence occurred in 30 % of patients but could be successfully treated with re
      operations in some cases. Various monoclonal antibodies are currently available
      and achieve a median survival time of up to 17 months. Pulmonary metastasectomy
      is the treatment of choice in selected patients; however, in the future the
      benefits should be revalidated in comparison with pharmaceuticals of the current
      generation. 

PMID- 25576145
TI  - [Abscopal effect in the treatment of malignant melanoma].
AB  - BACKGROUND: The clearance of non-irradiated tumors after localized radiation
      therapy is known as the abscopal effect. CASE REPORT: In the present case report
      we initiated a combined therapeutic approach based on sequential administration
      of ipilimumab plus temozolomide in combination with radiotherapy. The treatment
      regime was well tolerated and resulted in unusually long disease stabilization
      and in a complete response of brain and kidney metastases. Thus, it is speculated
      that the clinical response was the result of an abscopal effect. CONCLUSION: The
      present case report highlights the possible clinical benefit of the abscopal
      effect in the treatment of malignant melanoma.

PMID- 25576146
TI  - [Nonallergic comorbidities of atopic dermatitis].
AB  - BACKGROUND: Recognizing the whole spectrum of comorbidities related to atopic
      dermatitis (AD) is prerequisite for adequate, patient-centered care. OBJECTIVES:
      Based on systematic reviews (SRs) and published case-control studies, the current
      evidence on nonallergic comorbidities of AD is summarized. MATERIALS AND METHODS:
      A comprehensive systematic literature search was performed in Medline and Embase
      (Search period: through 15 November 2014). RESULTS: In total, nine systematic
      reviews were included. Six reviews investigating the association between AD and
      cancer suggested a decreased risk of glioma, meningioma, and acute lymphoblastic
      leukemia in patients with current or previous AD. One SR reported a consistent
      positive association of AD with attention deficit hyperactivity disorder. In
      comparison, two SRs focusing on the relationship between AD and diabetes mellitus
      type 1 and multiple sclerosis showed that there is no evidence supporting an
      association. A further screening of individual observational studies concerning
      immunological and psychiatric diseases pointed out that AD seems to be a
      significant risk factor for Crohn's disease, affective, schizophrenic, and
      behavior disorders. CONCLUSION: Further longitudinal studies are needed to verify
      the existence of causal relationships. Interdisciplinary working groups are
      desirable to investigate explanations for genetic and physiologic mechanisms of
      described associations between AD and nonallergic comorbidities.

PMID- 25576147
TI  - Do Statins Reduce the Health and Health Care Costs of Obesity?
AB  - CONTEXT: Obesity impacts both individual health and, given its high prevalence,
      total health care spending. However, as medical technology evolves, health
      outcomes for a number of obesity-related illnesses improve. This article examines
      whether medical innovation can mitigate the adverse health and spending
      associated with obesity, using statins as a case study. Because of the
      relationship between obesity and hypercholesterolaemia, statins play an important
      role in the medical management of obese individuals and the prevention of costly
      obesity-related sequelae. METHODS: Using well-recognized estimates of the health
      impact of statins and the Future Elderly Model (FEM)-an established dynamic
      microsimulation model of the health of Americans aged over 50 years-we estimate
      the changes in life expectancy, functional status and health care costs of
      obesity due to the introduction and widespread use of statins. RESULTS: Life
      expectancy gains of statins are estimated to be 5-6 % greater for obese
      individuals than for healthy-weight individuals, but most of these additional
      gains are associated with some level of disability. Considering both medical
      spending and the value of quality-adjusted life-years, statins do not
      significantly alter the costs of class 1 and 2 obesity (body mass index [BMI]
      >=30 and >=35 kg/m(2), respectively) and they increase the costs of class 3
      obesity (BMI >=40 kg/m(2)) by 1.2 %. CONCLUSIONS: Although statins are very
      effective medications for lowering the risk of obesity-associated illnesses, they
      do not significantly reduce the costs of obesity.

PMID- 25576149
TI  - Accelerated formulation development of monoclonal antibodies (mAbs) and mAb-based
      modalities: review of methods and tools.
AB  - More therapeutic monoclonal antibodies and antibody-based modalities are in
      development today than ever before, and a faster and more accurate drug discovery
      process will ensure that the number of candidates coming to the biopharmaceutical
      pipeline will increase in the future. The process of drug product development
      and, specifically, formulation development is a critical bottleneck on the way
      from candidate selection to fully commercialized medicines. This article reviews
      the latest advances in methods of formulation screening, which allow not only the
      high-throughput selection of the most suitable formulation but also the
      prediction of stability properties under manufacturing and long-term storage
      conditions. We describe how the combination of automation technologies and high
      throughput assays creates the opportunity to streamline the formulation
      development process starting from early preformulation screening through to
      commercial formulation development. The application of quality by design (QbD)
      concepts and modern statistical tools are also shown here to be very effective in
      accelerated formulation development of both typical antibodies and complex
      modalities derived from them. 

PMID- 25576148
TI  - Cost-of-illness studies for bipolar disorder: systematic review of international
      studies.
AB  - BACKGROUND AND OBJECTIVES: Bipolar disorder (BD) may result in a greater burden
      than all forms of cancer, Alzheimer's disease and epilepsy. Cost-of-illness (COI)
      studies provide useful information on the economic burden that BD imposes on a
      society. Furthermore, COI studies are pivotal sources of evidence used in
      economic evaluations. This study aims to give a general overview of COI studies
      for BD and to discuss methodological issues that might potentially influence
      results. This study also aims to provide recommendations to improve practice in
      this area, based on the review. METHODS: A search was performed to identify COI
      studies of BD. The following electronic databases were searched: MEDLINE, EMBASE,
      PsycInfo, Cochrane Database of Systematic Reviews, HMIC and openSIGLE. The
      primary outcome of this review was the annual cost per BD patient. A narrative
      assessment of key methodological issues was also included. Based on these
      findings, recommendations for good practice were drafted. RESULTS: Fifty-four
      studies were included in this review. Because of the widespread methodological
      heterogeneity among included studies, no attempt has been made to pool results of
      different studies. Potential areas for methodological improvement were
      identified. These were: description of the disease and population, the approach
      to deal with comorbidities, reporting the rationale and impact for choosing
      different cost perspectives, and ways in which uncertainty is addressed.
      CONCLUSIONS: This review showed that numerous COI studies have been conducted for
      BD since 1995. However, these studies employed varying methods, which limit the
      comparability of findings. The recommendations provided by this review can be
      used by those conducting COI studies and those critiquing them, to increase the
      credibility and reporting of study results.

PMID- 25576150
TI  - Prevalence of silent vertebral fractures detected by vertebral fracture
      assessment in young Portuguese men with hyperthyroidism.
AB  - BACKGROUND: Hyperthyroidism is a risk factor for reduced bone mineral density
      (BMD) and osteoporotic fractures. Vertebral fracture assessment (VFA) by dual
      energy X-ray absorptiometry (DXA) is a radiological method of visualization of
      the spine, which enables patient comfort and reduced radiation exposure.
      OBJECTIVES: This study was carried out to evaluate BMD and the prevalence of
      silent vertebral fractures in young men with hyperthyroidism. DESIGN: We
      conducted a cross-sectional study in a group of Portuguese men aged up to 50
      years and matched in hyperthyroidism (n=24) and control (n=24) groups. MATERIALS
      AND METHODS: A group of 48 Portuguese men aged up to 50 years was divided and
      matched in hyperthyroidism (n=24) and control (n=24) groups. BMD (g/cm(2)) at L1
      L4, hip, radius 33%, and whole body as well as the total body masses (kg) were
      studied by DXA. VFA was used to detect fractures and those were classified by
      Genant's semiquantitative method. No patient had previously been treated for
      hyperthyroidism, osteoporosis, or low bone mass. Adequate statistical tests were
      used. RESULTS: The mean age, height, and total fat mass were similar in both
      groups (P>=0.05). The total lean body mass and the mean BMD at lumbar spine, hip,
      and whole body were significantly decreased in the hyperthyroidism group. In this
      group, there was also a trend for an increased prevalence of reduced
      BMD/osteoporosis and osteoporotic vertebral fractures. CONCLUSIONS: The results
      obtained using VFA technology (confirmed by X-ray) suggest that the BMD changes
      in young men with nontreated hyperthyroidism may lead to the development of
      osteoporosis and vertebral fractures. This supports the pertinence of using VFA
      in the routine of osteoporosis assessment to detect silent fractures precociously
      and consider early treatment.

PMID- 25576152
TI  - Computer and online health information literacy among Belgrade citizens aged 66
      89 years.
AB  - Computer users over 65 years of age in Serbia are rare. The purpose of this study
      was to (i) describe main demographic characteristics of computer users older than
      65; (ii) evaluate their online health information literacy and (iii) assess
      factors associated with computer use in this population. Persons above 65 years
      of age were recruited at the Community Health Center 'Vracar' in Belgrade from
      November 2012 to January 2013. Data were collected after medical checkups using a
      questionnaire. Of 480 persons who were invited to participate 354 (73.7%) agreed
      to participate, while 346 filled in the questionnaire (72.1%). A total of 70
      (20.2%) older persons were computer users (23.4% males vs. 17.7% females). Of
      those, 23.7% explored health-related web sites. The majority of older persons who
      do not use computers reported that they do not have a reason to use a computer
      (76.5%), while every third senior (30.4%) did not own a computer. Predictors of
      computer use were being younger [odds ratio (OR) = 2.14, 95% confidence interval
      (CI) 1.30-4.04; p = 0.019], having less members of household (OR = 2.97, 95% CI
      1.45-6.08; p = 0.003), being more educated (OR = 3.53, 95% CI 1.88-6.63; p =
      0.001), having higher income (OR = 2.31, 95% CI 1.17-4.58; p = 0.016) as well as
      fewer comorbidities (OR = 0.42, 95% CI 0.23-0.79; p = 0.007). Being male was
      independent predictor of online health information use at the level of marginal
      significance (OR = 4.43, 95% CI 1.93-21.00; p = 0.061). Frequency of computer and
      Internet use among older adults in Belgrade is similar to other populations.
      Patterns of Internet use as well as non-use demonstrate particular socio-cultural
      characteristics. 

PMID- 25576153
TI  - Trials of Ebola vaccine set to begin in west Africa.

PMID- 25576151
TI  - Collaboration of geldanamycin-activated P70S6K and Hsp70 against beta-amyloid
      induced hippocampal apoptosis: an approach to long-term memory and learning.
AB  - One of the neuropathological hallmarks of Alzheimer's disease (AD) is the
      accumulation of beta-amyloid peptides (Abeta) in senile plaques. Abeta-induced
      oxidative stress is believed to be responsible for degeneration and apoptosis of
      neurons and consequent cognitive and memory deficits. Here, we investigated the
      possible neuroprotective effect of the heat shock protein 90 (Hsp90) inhibitor
      geldanamycin (GA) against amyloid pathogenesis in adult male Wistar rats. GA or
      vehicle was injected into the lateral cerebral ventricles of rats 24 h before
      injection of Abeta (1-42) in CA1 area of hippocampus. The learning and memory of
      the rats were assessed 7 days after injection of Abeta using passive avoidance
      (PA) task. As potential contributing factors in Abeta-induced memory decline, we
      evaluated apoptotic markers and also used terminal-transferase UTP nick end
      labeling (TUNEL) technique to detect apoptosis in the hippocampus of Abeta
      injected rats. Our behavioral data suggest that GA pretreatment can significantly
      suppress memory deficits in Abeta-injected rats. There was also not only a marked
      increase in Hsp70 level but also upregulated 70 kDa ribosomal protein S6 kinase
      (p70S6K) in the hippocampus of GA-treated groups with a reduction in apoptotic
      factors including caspase-3, poly (ADP-ribose) polymerase, Bax/Bcl-2 ratio, and
      TUNEL-positive cells as well. Thus, we conclude that GA exerts its protective
      effects against Abeta (1-42) toxicity and memory deficits, at least in part, by
      upregulating of Hsp70 and P70S6K. 

PMID- 25576154
TI  - Energy deficit is clinically relevant for critically ill patients: no.

PMID- 25576155
TI  - Aberrant internal carotid artery: a risky condition for tracheal intubation.

PMID- 25576156
TI  - Energy deficit is clinically relevant for critically ill patients: yes.

PMID- 25576157
TI  - The Iatroref study: medical errors are associated with symptoms of depression in
      ICU staff but not burnout or safety culture.
AB  - PURPOSE: Staff behaviours to optimise patient safety may be influenced by
      burnout, depression and strength of the safety culture. We evaluated whether
      burnout, symptoms of depression and safety culture affected the frequency of
      medical errors and adverse events (selected using Delphi techniques) in ICUs.
      METHODS: Prospective, observational, multicentre (31 ICUs) study from August 2009
      to December 2011. RESULTS: Burnout, depression symptoms and safety culture were
      evaluated using the Maslach Burnout Inventory (MBI), CES-Depression scale and
      Safety Attitudes Questionnaire, respectively. Of 1,988 staff members, 1,534 (77.2
      %) participated. Frequencies of medical errors and adverse events were
      804.5/1,000 and 167.4/1,000 patient-days, respectively. Burnout prevalence was 3
      or 40 % depending on the definition (severe emotional exhaustion,
      depersonalisation and low personal accomplishment; or MBI score greater than -9).
      Depression symptoms were identified in 62/330 (18.8 %) physicians and 188/1,204
      (15.6 %) nurses/nursing assistants. Median safety culture score was 60.7/100
      [56.8-64.7] in physicians and 57.5/100 [52.4-61.9] in nurses/nursing assistants.
      Depression symptoms were an independent risk factor for medical errors. Burnout
      was not associated with medical errors. The safety culture score had a limited
      influence on medical errors. Other independent risk factors for medical errors or
      adverse events were related to ICU organisation (40 % of ICU staff off work on
      the previous day), staff (specific safety training) and patients (workload). One
      on-one training of junior physicians during duties and existence of a hospital
      risk-management unit were associated with lower risks. CONCLUSIONS: The frequency
      of selected medical errors in ICUs was high and was increased when staff members
      had symptoms of depression.

PMID- 25576158
TI  - Myths about critical care echocardiography: the ten false beliefs that
      intensivists should understand.

PMID- 25576160
TI  - Escovopsis trichodermoides sp. nov., isolated from a nest of the lower attine ant
      Mycocepurus goeldii.
AB  - Currently, five species are formally described in Escovopsis, a specialized
      mycoparasitic genus of fungus gardens of attine ants (Hymenoptera: Formicidae:
      tribe Attini). Four species were isolated from leaf-cutting ants in Brazil,
      including Escovopsis moelleri and Escovopsis microspora from nests of Acromyrmex
      subterraneus molestans, Escovopsis weberi from a nest of Atta sp. and Escovopsis
      lentecrescens from a nest of Acromyrmex subterraneus subterraneus. The fifth
      species, Escovopsis aspergilloides was isolated from a nest of the higher attine
      ant Trachymyrmex ruthae from Trinidad. Here, we describe a new species,
      Escovopsis trichodermoides isolated from a fungus garden of the lower attine ant
      Mycocepurus goeldii, which differs from the five other species by highly
      branched, trichoderma-like conidiophores lacking swollen vesicles, with reduced
      conidiogenous cells and distinctive conidia morphology. Phylogenetic analyses
      based on partial tef1 gene sequences support the distinctiveness of this species.
      A portion of the internal transcribed spacers of the nuclear rDNA was sequenced
      to serve as a DNA barcode. Future molecular and morphological studies in this
      group of fungi will certainly unravel the taxonomic diversity of Escovopsis
      associated with fungus-growing ants. 

PMID- 25576159
TI  - Testosterone regulates thyroid cancer progression by modifying tumor suppressor
      genes and tumor immunity.
AB  - Cancer gender disparity has been observed for a variety of human malignancies.
      Thyroid cancer is one such cancer with a higher incidence in women, but more
      aggressive disease in men. There is scant evidence on the role of sex hormones on
      cancer initiation/progression. Using a transgenic mouse model of follicular
      thyroid cancer (FTC), we found castration led to lower rates of cancer in females
      and less advanced cancer in males. Mechanistically, less advanced cancer in
      castrated males was due to increased expression of tumor suppressor (Glipr1,
      Sfrp1) and immune-regulatory genes and higher tumor infiltration with M1
      macrophages and CD8 cells. Functional study showed that GLIPR1 reduced cell
      growth and increased chemokine secretion (Ccl5) that activates immune cells. Our
      data demonstrate that testosterone regulates thyroid cancer progression by
      reducing tumor suppressor gene expression and tumor immunity. 

PMID- 25576161
TI  - Combined methylation of p16 and hMLH1 (CMETH2) discriminates a subpopulation with
      better prognosis in colorectal cancer patients with microsatellite instability
      tumors.
AB  - The aim of this study was to determine the frequency of p16 and hMLH1 genes
      simultaneous methylation in colorectal cancer patients with Microsatellite
      Instability (MSI) tumors. We also wanted to analyze the relationship with other
      clinical features, with BRAF gene V600E mutation and with prognosis. Samples from
      fifty one patients with MSI positive sporadic colorectal cancer were included.
      DNA was extracted from tumor samples. Promoter methylation was analyzed using
      bisulfite modification and was detected by quantitative methylation-specific PCR.
      BRAF gene was amplified using specific primers and mutations were detected by
      real time PCR. Simultaneous methylation was transformed in a new variable called
      CMETH2. Frequency of CMETH2 was analyzed and compared with other
      clinicopathological variables. 33.3 % of patients were positive for CMETH2 and 25
      % had BRAF V600E mutation. CMETH2 was related with proximal location, with poorly
      differentiated tumors and with BRAF V600E mutation. CMETH2 only showed influence
      in the overall survival (OS) in patients with distal tumors. However, with regard
      to the disease free survival (DFS) measure, CMETH2 was independent prognostic
      factor. We were able to discriminate tumors with high methylation features using
      a transformation analysis of variables into a new computed one (CMETH2). CMETH2
      has demonstrated to be a useful prognostic factor in MSI tumors. The prognostic
      value of CMETH2 in DFS was independent of other clinicopathological variables.
      The use of CMETH2 could help in the election of the best therapeutic alternative
      for CCR patients with MSI tumors.

PMID- 25576163
TI  - 'Deferred or chickened out?' Decision making among male carers of people with
      dementia.
AB  - In this paper, we present new insight into the ways in which carers of people
      with dementia make decisions in the context of seemingly declining autonomy and
      freedom associated with the condition. Our focus is on the ways in which carers
      reflect on decisions made in different temporal contexts (day-to-day, medium- and
      long term). Drawing on data and analysis from in-depth interviews with male
      informal carers of women with mild to moderate dementia living in the northwest
      of England, we outline how the decision-making process is dependent on the
      temporality of the decisions. Arguably unsurprisingly, we found that short-term
      or 'day-to-day' decisions were made with input from those cared for, while longer
      term decisions were deferred until a point when necessity meant carers had to
      make decisions themselves. However, and importantly, carers were aware of the
      implications of how they were making decision, including the potential impact in
      terms of partial withdrawal, or even full denial, of autonomy of those they care
      for. Consequently, we argue that carers adopt a form of practised autonomy to
      negotiate the complexity of everyday decision making while managing longer term
      uncertainty and anxiety.

PMID- 25576162
TI  - Conjugation and deconjugation reactions within the fetoplacental compartment in a
      sheep model: a key factor determining bisphenol A fetal exposure.
AB  - The widespread human exposure to bisphenol A (BPA), an endocrine disruptor
      targeting developmental processes, underlines the need to better understand the
      mechanisms of fetal exposure. Animal studies have shown that at a late stage of
      pregnancy BPA is efficiently conjugated by the fetoplacental unit, mainly into
      BPA-glucuronide (BPA-G), which remains trapped within the fetoplacental unit.
      Fetal exposure to BPA-G might in turn contribute to in situ exposure to bioactive
      BPA, following its deconjugation into parent BPA at the level of fetal sensitive
      tissues. The objectives of our study were 1) to characterize the BPA glucurono-
      and sulfoconjugation capabilities of the ovine fetal liver at different
      developmental stages, 2) to compare hepatic conjugation activities in human and
      sheep, and 3) to evaluate the extent of BPA conjugation and deconjugation
      processes in placenta and fetal gonads. At an early stage of pregnancy, and
      despite functional sulfoconjugation activity, ovine fetuses expressed low hepatic
      BPA conjugation capabilities, suggesting that this stage of development
      represents a critical window in terms of BPA exposure. Conversely, the late ovine
      fetus expressed an efficient detoxification system that metabolized BPA into BPA
      G. Hepatic glucuronidation activities were quantitatively similar in adult sheep
      and humans. In placenta, BPA conjugation and BPA-G deconjugation activities were
      relatively balanced, whereas BPA-G hydrolysis was systematically higher than BPA
      conjugation in gonads. The possible reactivation of BPA-G into BPA could
      contribute to an increased exposure of fetal sensitive tissues to bioactive BPA
      in situ. 

PMID- 25576164
TI  - Establishing a complex surgical oncology program with low morbidity and mortality
      at a community hospital.
AB  - BACKGROUND: We report our experience with a large volume of complex oncologic
      resections and describe the framework necessary to develop a program with low
      morbidity and mortality in a community hospital. METHODS: From August 2010 to May
      2014, 224 consecutive patients underwent abdominal oncological resection, at a
      community hospital by a single surgeon (R.N.B.). Cases included pancreatic,
      gastric, hepatobiliary, colorectal, hyperthermic intraperitoneal chemotherapy
      with cytoreduction, splenic, and sarcoma resections. We retrospectively reviewed
      our prospectively maintained database and evaluated postoperative complications.
      RESULTS: There was no 0, 30-, 60-, or 90-day mortality. The complication rate was
      44%, including 5% grade I, 28% grade II, 9% grade III, and 1% grade IV
      complications. The median length of stay was 8 days. Mean follow-up for the
      entire group was 643 days. CONCLUSION: Our study demonstrates that complex
      oncologic resections can be safely performed in the community setting if a well
      organized, surgeon-led multidisciplinary team is assembled.

PMID- 25576165
TI  - African-American women have equivalent outcomes following autologous free flap
      breast reconstruction despite greater preoperative risk factors.
AB  - BACKGROUND: Disparities along racial and ethnic lines exist in breast cancer
      treatment and reconstruction. This study compares preoperative characteristics
      among female breast cancer patients who received autologous breast reconstruction
      to determine if race affects clinical outcomes. METHODS: Women receiving
      autologous breast reconstruction at a single institution from 2005 to 2011 were
      identified within a prospectively maintained database. Preoperative risk factors
      and rates of postoperative morbidity and mortality were assessed with respect to
      race. RESULTS: African-American patients had significantly higher rates of
      preoperative comorbidities than Caucasian patients. Despite the heightened
      preoperative risk factors, postoperative complications did not significantly
      differ between racial categories. CONCLUSION: As the alleviation of healthcare
      disparities remains a focus of healthcare reform, these findings are beneficial
      in further educating African-American breast cancer patients and their providers
      of the safe and viable option of autologous tissue transfer for breast
      reconstruction.

PMID- 25576166
TI  - A rare case of jejuno-ileal intussusception secondary to a gastrointestinal
      stromal tumour.
AB  - Gastrointestinal stromal tumours (GISTs) are rare tumours, making up 0.2-1% of
      gastrointestinal malignancies [Zakaria and Daradkeh (Jejunojejunal
      intussusception induced by a gastrointestinal stromal tumour. Case Rep Surg 2012;
      2022: :173680)]. Their relative rarity combined with non-specific presentation
      results in tumours often remaining undiagnosed until surgery or histological
      examination [Martis et al. (A rare case of jejunojejunal intussusception in an
      adult. Indian J Surg 2013; 75: (Suppl 1):18-20)]. Presentation as a lead point
      for intussusception is particularly rare. We present the first case of GIST
      leading to intussusception at the jejuno-ileal junction in an otherwise well
      patient prior to presentation. Provisional diagnosis was made during emergency
      laparotomy, and confirmed through histological analysis. A typical
      immunohistochemical profile was identified, after which the patient was commenced
      on adjuvant imatinib therapy. We discuss classical presentation of
      intussusception and GIST. Further considerations of the investigation and
      treatment options of GISTs are also presented. 

PMID- 25576167
TI  - Use of amniotic membrane graft in the surgical management of cicatricial
      ectropion associated with cetuximab therapy.
AB  - Cetuximab (Erbitux) is an antiepidermal growth factor receptor (EGFR) monoclonal
      antibody that has been shown to delay the progression of metastatic colorectal
      cancer. The cutaneous side effects of cetuximab resulting from its effects on
      normal epidermal cells are well established. Periocular side effects, including
      blepharitis, trichomegaly, dry eye and conjunctivitis, have also been reported.
      We present a case of cicatricial ectropion associated with cetuximab therapy
      successfully managed with surgical repair using amniotic membrane graft. A 60
      year-old man presented with bilateral lower eyelid cicatricial ectropion
      developing 3 days after the addition of cetuximab therapy to his baseline
      chemotherapeutic regimen. This was successfully managed with surgical repair
      using an amniotic membrane graft. Surgical repair with the amniotic membrane
      graft is a viable treatment option for cicatricial ectropion associated with EGFR
      inhibitor therapy. 

PMID- 25576168
TI  - A case series of two glomus tumors of the gastrointestinal tract.
AB  - Two recent cases of glomus tumors (GTs) of the gastrointestinal tract presented
      with symptoms of GI bleeding. GTs, typically benign lesions of mesenchymal
      origin, are rarely seen in the GI tract, and most commonly involve the distal
      appendages. This case series discusses the tumor biology, presentation, imaging,
      endoscopic findings, pathology and management of GTs. While diagnosis of GTs is
      typically made on final surgical pathology, there are defining characteristics
      that can separate a GT from a gastrointestinal stromal tumor on endoscopic
      ultrasound (EUS) and CT imaging. The classic pathological findings are discussed,
      and surgical decision-making is reviewed. New developments in the form of EUS
      guided biopsy and endoscopic submucosal dissection present new avenues for
      diagnosis and treatment of submucosal lesions of the GI tract, including GTs.
      While typically a benign tumor requiring no adjuvant therapy, this study
      discusses some very rare cases of metastatic GT in the literature. 

PMID- 25576169
TI  - Normal anatomy and anatomic variants of vascular foramens in the cervical
      vertebrae: a paleo-osteological study and review of the literature.
AB  - We investigated 923 cervical vertebrae belonging to late-antiquity and medieval
      skeletal remains and assessed the qualitative and quantitative structural
      characteristics of transverse foramens (TF) and additional vascular canals. We
      also reviewed the pertinent literature. Double TF were chiefly observed in C6
      (with a right/left side prevalence of 35.7 and 44.4%, respectively) and C5
      vertebrae (23.6 and 23.9%, right/left side, respectively), while unclosed TF were
      mainly documented in C1 vertebrae (8.4%). Retrotransverse canal and
      retrotransverse groove were present in 8.5 and 17.8%, respectively, of C1
      vertebrae examined, while arcuate foramens and supertransverse foramens were
      found in 7.3 and 3.7% of specimens, respectively. TF diameter decreased from C6
      to C2 vertebrae, being smallest in C7 and greatest in C1 vertebrae, with no
      left/right significant difference. There was a significant correlation between TF
      diameter and stature, but only on the right side. The mean area of the arcuate
      foramen was lower than the mean area of the ipsilateral TF (24.5 +/- 5.7 vs 28.5
      +/- 7.7 mm(2), respectively; p = 0.048), possibly causing compression of the
      vertebral artery within the arcuate foramen. The study of human vertebrae
      excavated from archaeological sites is a simple and effective way to analyze the
      morphology and quantitative anatomy of vascular foramens.

PMID- 25576170
TI  - Monthly microperimetry (MP1) measurement of macular sensitivity after
      dexamethasone implantation (Ozurdex) in retinal vein occlusions.
AB  - PURPOSE: To evaluate changes in macular sensitivity as measured via
      microperimetry (MP) in patients with macular edema (ME) secondary to retinal vein
      occlusion (RVO) after dexamethasone implantation (DEX implantation, Ozurdex), in
      comparison to distance visual acuity, reading ability, and spectral domain
      optical coherence tomography (SD-OCT). METHODS: Twenty-three patients with ME
      secondary to RVO were treated with a DEX implantation in this prospective,
      observational case study. Patients were controlled at baseline and then monthly
      with microperimetry and assessment of distance visual acuity, reading ability,
      and SD- OCT. Side effects of the DEX implant were monitored by measuring the
      intraocular pressure (IOP) and lens grading with Lens Opacities Classification
      System (LOCS) charts. RESULTS: The 23 patients with RVO included 16 patients with
      branch retinal vein occlusion (BRVO) and 7 patients with central retinal vein
      occlusion (CRVO). Improvement in distance visual acuity, reading ability, and in
      central 8-points microperimetry showed statistical significance from month 1 to
      3, whereas the 40-points microperimetry improved with statistical significance
      from month 1 to 2. The reduction of central retinal thickness measured with SD
      OCT remained statistically significant until month 4. Subgroup analysis of
      patients with BRVO and CRVO confirmed the best test results observed at month two
      after DEX implantation. CONCLUSIONS: The highest macular sensitivity was measured
      two months after DEX implantation. This corresponds to the best test results for
      distance visual acuity, reading ability, and SD-OCT observed two months after
      treatment.

PMID- 25576171
TI  - A case-control study to assess aspirin as a risk factor of bleeding in
      rhegmatogenous retinal detachment surgery.
AB  - PURPOSE: The purpose of this study was to evaluate the hemorrhagic risk factors
      during the management of primary rhegmatogenous retinal detachment (RD). METHODS:
      Three hundred and twenty-two patients with (n = 74) or without (n = 248) bleeding
      (anterior segment, choroidal, intravitreal and/or subretinal) during or after RD
      surgery were included in this case-control study. Exclusion criteria were:
      history of trauma, vitreoretinal surgery, diabetic retinopathy, and taking
      clopidogrel and/or a vitamin K antagonist. Univariate and multivariate analyses
      were performed to identify risk factors of perioperative bleeding. RESULTS:
      Aspirin was not significantly associated with bleeding complications during or
      after surgery (p = 0.8). Scleral buckling (with cryotherapy and gas tamponnade)
      was performed in 47 % of the cases and pars plana vitrectomy in 53 % of the
      cases. Independent risk factors of perioperative hemorrhage were the number of
      cryotherapy impacts (odds ratio =1.12 [1.06; 1.20], 95 % confidence interval),
      transscleral drainage (OR = 4.22 [1.62; 10.98]), and use of pars plana vitrectomy
      (OR = 3.39 [1.36; 8.47]). Bleeding complications were associated with a lower
      single-operation anatomical success rate (74 % vs 84 %, p = 0.03). There was also
      a trend toward an association between bleeding complications, a higher total
      number of RD recurrences (0.19 +/- 0.5 in the non-bleeding group vs 0.34 +/- 0.6,
      p = 0.06), and a lower final visual acuity (0.5 +/- 0.6 logMAR vs 0.7 +/- 0.7, p
      = 0.09). CONCLUSION: This case-control study suggests that aspirin is not a major
      risk factor of hemorrhagic complications during and after RD surgery.
      Perioperative bleeding leads to a lower single-operation anatomic success rate.

PMID- 25576173
TI  - What does my avatar say about me? Inferring personality from avatars.
AB  - Many individuals now meet and develop friendships while online. As a result,
      people must form impressions of online acquaintances based on that person's
      online representation. Here, we investigate personality inferences and intentions
      to befriend based solely on simple avatars (i.e., customized cartoon
      representations of the self). Our data show that some traits are more easily
      inferred from avatars than others, avatars can communicate accurate and
      distinctive information regarding personality, and individuals with certain
      personality traits create avatars that are more likely to be perceived
      accurately. We also found that agreeable and normative individuals created
      avatars that elicited more desire for friendship from others, implying that the
      impression given by one's digital avatars may have social consequences.

PMID- 25576172
TI  - CD40 ligand induces expression of vascular cell adhesion molecule 1 and E
      selectin in orbital fibroblasts from patients with Graves' orbitopathy.
AB  - PURPOSE: The aim of this study was to detect the effect of the CD40 ligand
      (CD40L) on the expression of vascular cell adhesion molecule 1 (VCAM-1) and E
      Selectin in orbital fibroblasts (OFs) from patients with Graves' orbitopathy
      (GO), as well as the signaling pathways involved in this effect. METHODS: OFs
      were isolated from orbital tissues obtained from patients with severe GO who were
      undergoing orbital decompression surgery. VCAM-1 and E-selectin RNA and protein
      expression levels were quantified in OFs stimulated with soluble CD40L (sCD40L).
      RNA and protein quantification was performed with real-time polymerase chain
      reaction (PCR) and western blot analysis. Cytoplasmic and nuclear fractions were
      isolated in order to detect the nuclear translocation of nuclear factor-kappaB
      (NF-kappaB). Signaling pathway inhibitors were applied to determine the pathways
      involved. RESULTS: Compared to unstimulated OFs, the mRNA and protein levels of
      VCAM-1 and E-selectin in OFs incubated with sCD40L were significantly increased.
      This was observed in dose- and time-course experiments, and the inductive effects
      of sCD40L were much weaker in OFs from healthy donors. At the same time, we
      observed that CD40L induced nuclear translocation of NF-kappaB, also in a dose-
      and time-dependent manner. The up-regulation of VCAM-1 and E-selectin, as well as
      the NF-kappaB nuclear translocation induced by CD40L, was significantly
      attenuated by inhibitors targeting mitogen-activated protein kinases (MAPKs),
      phosphatidylinositol 3-kinase (PI3K), and NF-kappaB. CONCLUSIONS: CD40L
      demonstrated the ability to up-regulate the expression of VCAM-1 and E-selectin
      at the pre-translational level in OFs from patients with GO. The MAPK and PI3K
      pathways and NF-kappaB may play important roles in CD40L-induced VCAM-1 and E
      selectin expression.

PMID- 25576175
TI  - Factors affecting the quality of life of young neurosurgeons: a survey.

PMID- 25576174
TI  - The influence of MU-opioid and noradrenaline reuptake inhibition in the
      modulation of pain responsive neurones in the central amygdala by tapentadol in
      rats with neuropathy.
AB  - Treatments for neuropathic pain are either not fully effective or have
      problematic side effects. Combinations of drugs are often used. Tapentadol is a
      newer molecule that produces analgesia in various pain models through two
      inhibitory mechanisms, namely central MU-opioid receptor (MOR) agonism and
      noradrenaline reuptake inhibition. These two components interact synergistically,
      resulting in levels of analgesia similar to opioid analgesics such as oxycodone
      and morphine, but with more tolerable side effects. The right central nucleus of
      the amygdala (CeA) is critical for the lateral spinal ascending pain pathway,
      regulates descending pain pathways and is key in the emotional-affective
      components of pain. Few studies have investigated the pharmacology of limbic
      brain areas in pain models. Here we determined the actions of systemic tapentadol
      on right CeA neurones of animals with neuropathy and which component of
      tapentadol contributes to its effect. Neuronal responses to multimodal peripheral
      stimulation of animals with spinal nerve ligation or sham surgery were recorded
      before and after two doses of tapentadol. After the higher dose of tapentadol
      either naloxone or yohimbine were administered. Systemic tapentadol resulted in
      dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both
      naloxone and yohimbine reversed this effect to an extent that was modality
      selective. The interactions of the components of tapentadol are not limited to
      the synergy between the MOR and alpha2-adrenoceptors seen at spinal levels, but
      are seen at this supraspinal site where suppression of responses may relate to
      the ability of the drug to alter affective components of pain. 

PMID- 25576176
TI  - Relationship between physicochemical properties and enzymatic hydrolysis of
      sugarcane bagasse varieties for bioethanol production.
AB  - The structural and physicochemical characteristics are associated with resistance
      of plant cell walls to saccharification by enzymes. The effect of physicochemical
      properties on glucose yield of bagasse from different varieties of sugarcane at
      low and high enzyme dosages was investigated. The result showed that glucose
      yield at low enzyme dosage was positively linear correlated with the yield at
      high enzyme dosage, for both the untreated and pretreated materials. The
      pretreatment significantly increased the accessibility of substrates by enzyme
      due to the increase of internal and external surface area. Glucose yield also
      showed a linear correlation with dye adsorption. However, the increase in glucose
      yield as a result of pretreatment did not correlate with the increases in
      crystallinity index and decreases in degree of polymerization. The Principal
      Component Analysis of infrared data indicated that lignin was the main component
      that differentiated the varieties before and after pretreatment. These results
      suggested that the key differences in pretreatment responses among varieties
      could be mainly attributed to their differences in the internal and external
      surface area after pretreatment. 

PMID- 25576177
TI  - Child neurology practice guidelines: past, present, and future.
AB  - BACKGROUND: Practice guidelines have been developed in child neurology during the
      last fifteen years to address important clinical questions and provide evidence
      based recommendations for patient care. METHODS: This review describes the
      guideline development process and how it has evolved to meet the needs of child
      neurologists. RESULTS: Several current child neurology guidelines are reviewed
      and the advantages and disadvantages of guidelines, as well as the legal
      consequences of using them to determine a standard of care are discussed. The
      future of guidelines and of their influence on integrated support systems also is
      considered. CONCLUSIONS: Child neurology practice guidelines are a helpful
      resource for clinicians, families and institutions as they provide evidence-based
      recommendations concerning the diagnosis and management of common neurological
      conditions affecting children. Incorporating consensus processes has allowed
      expansion of clinically relevant recommendations that has increased the utility
      of guidelines.

PMID- 25576178
TI  - Comparison of Health Care Resource Utilization by Immigrants Versus Native
      Elderly People.
AB  - To compare the utilization of health care resources (drug prescriptions, hospital
      admissions and health care services) by immigrant versus native elderly people
      (65 years or more), by using administrative database of the Lombardy Region. For
      each immigrant (an older people born out of Italy), one person born in Lombardy
      (native) was randomly selected and matched by age, sex and general practitioner.
      The 25,508 immigrants selected were less prescribed with at least one drug (OR
      0.72, 95 % CI 0.67-0.76) and had a lesser use of health care services (OR 0.79,
      95 % CI 0.75-0.84) than natives. No statistically significant differences were
      found for hospital admission rates (OR 0.99, 95 % CI 0.99-1.04). A lower rate of
      health care resource utilization was observed in elderly immigrants who had been
      living in the host region for as many as 10 years.

PMID- 25576179
TI  - Use of Regional Data to Validate and Recalibrate Self-reported Hypertension:
      Highlighting Differences in Immigrant Groups in New York City.
AB  - Self-reported hypertension has not been validated in specific Hispanic subgroups
      (Puerto Ricans, Dominicans) and in Asian Americans. The objectives were to assess
      validity of self-reported hypertension in Hispanic and Asian American adults, and
      to recalibrate self-reported hypertension with measured values. Data were from
      the New York City Community Health Survey 2005-2008 and the Heart Follow-Up Study
      (HFUS) 2010 (included measured hypertension). Sensitivity and specificity were
      calculated in the HFUS data; recalibration was conducted using a previously
      described method by Mentz et al. Sensitivity was similar in Puerto Ricans and
      Dominicans versus whites. The differences in hypertension prevalence after
      recalibration were largest in Hispanics. No substantial differences occurred
      among Asian Americans. Factors such as low health literacy or insurance status
      are potential explanations for bias in self-reported hypertension among Hispanic
      subgroups. Surveillance systems may consider recalibration, potentially in areas
      with a high percentage of Hispanics or uninsured. 

PMID- 25576180
TI  - Breastfeeding and Asthmatic Symptoms in The Offspring of Latinas: The Role of
      Maternal Nativity.
AB  - Previous research has generally found exclusive breastfeeding to protect against
      asthma in young children. However, maternal nativity in a Latina population has
      not been assessed as a potential confounder or effect modifier. Using cross
      sectional data restricted to Latina mothers (n = 704) from a birth cohort in Los
      Angeles interviewed in 2003 and 2006, we estimated risk ratios (RR) for exclusive
      breastfeeding and asthmatic symptoms in the offspring. 56 children (8%) had
      asthmatic symptoms at age 3.5 years. We found a 49% reduction in risk of
      asthmatic symptoms with >3 months of exclusive breastfeeding (aRR 0.51, 95% CI
      0.28, 0.90). Foreign-born Latinas were more likely to initiate and continue
      breastfeeding for at least 3 months compared with US-born Latinas. Three or more
      months of exclusive breastfeeding reduced the risk of asthmatic symptoms in the
      offspring of Latinas, and maternal nativity did not confound or modify this
      association.

PMID- 25576181
TI  - [Behavioral concepts in the treatment of chronic pain].
AB  - In recent decades there has been much work on cognitive behavioral approaches to
      chronic pain. Now there is a considerable variety of concepts and interventions
      which share the same roots but differ in theoretical issues and application.
      Psychotherapeutic interventions are ideally embedded into an interdisciplinary
      setting and base on a bio-psycho-social perspective. Starting from a classical
      operant model we will describe the model of fear avoidance and the model of
      acceptance in the therapy of chronic pain. The latter have been influencing
      therapy and theory in recent years. The cognitive behavioral perspective on
      chronic pain has, therefore, not only become more differentiated and complex but
      also more complicated. 

PMID- 25576182
TI  - Changes in the mitochondrial antioxidant systems in neurodegenerative diseases
      and acute brain disorders.
AB  - Oxidative and nitrosative stress (ONS) contributes to the pathogenesis of most
      brain maladies, and the magnitude of ONS is related to the ability of cellular
      antioxidants to neutralize the accumulating reactive oxygen and nitrogen species
      (ROS/RNS). While the major ROS/RNS scavengers and regenerators of bio-oxidized
      molecules, superoxide dysmutases (SODs), glutathione (GSH), thioredoxin (Trx) and
      peroxiredoxin (Prx), are distributed in all cellular compartments. This review
      specifically focuses on the role of the systems operating in mitochondria. There
      is a growing consensus that the mitochondrial SOD isoform - SOD2 and GSH are
      critical for the cellular antioxidant defense. Variable changes of the expression
      or activities of one or more of the mitochondrial antioxidant systems have been
      documented in the brains derived from human patients and/or in animal models of
      neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), cerebral
      ischemia, toxic brain cell damage associated with overexposure to mercury or
      excitotoxins, or hepatic encephalopathy. In many cases, ambiguity of the
      responses of the different antioxidant systems in one and the same disease needs
      to be more conclusively evaluated before the balance of the changes is viewed as
      beneficial or detrimental. Modulation of the mitochondrial antioxidant systems
      may in the future become a target of antioxidant therapy. 

PMID- 25576183
TI  - SK channel activation modulates mitochondrial respiration and attenuates neuronal
      HT-22 cell damage induced by H2O2.
AB  - Previous studies established an essential role for small conductance calcium
      activated potassium (SK) channels in neuronal cell death pathways induced by
      glutamate excitotoxicity in cortical neurons in vitro and after cerebral ischemia
      in vivo. In addition to the intracellular calcium deregulation, glutamate-induced
      cell death also involves mechanisms of oxidative stress and mitochondrial
      dysfunction. Therefore, we sought to investigate whether SK channel activation
      might also affect mechanisms of intrinsic death pathways induced by reactive
      oxygen species (ROS) such as hydrogen peroxide (H2O2). Exposure of immortalized
      hippocampal HT-22 cells to H2O2 imposed activation of a cascade of intracellular
      toxic events resulting in intracellular ROS production, mitochondrial loss of
      function, and ultimately cell death. Using a pharmacological approach to activate
      SK channels with CyPPA, we demonstrated a reduction of H2O2-mediated
      intracellular ROS production and cell death. Interestingly, CyPPA mediated
      neuroprotection in conditions of extracellular calcium and/or pyruvate depletion,
      pointing to a neuroprotective role of mitochondrial SK channels. Moreover, CyPPA
      partially inhibited H2O2-induced mitochondrial superoxide production, but did not
      prevent mitochondrial membrane depolarization. CyPPA treatment resulted in slight
      ATP depletion and a reduction of mitochondrial respiration/oxygen consumption.
      These findings postulate that SK channels mediate a protective effect by
      preventing neuronal death from subsequent oxidative stress through an adaptive
      metabolic response at the level of mitochondria. Therefore, SK channel activation
      may serve as a therapeutic target, where mitochondrial dysfunction and related
      mechanisms of oxidative stress contribute to progressive degeneration and death
      of neurons. 

PMID- 25576184
TI  - Neuroprotective effects of the allosteric agonist of metabotropic glutamate
      receptor 7 AMN082 on oxygen-glucose deprivation- and kainate-induced neuronal
      cell death.
AB  - Although numerous studies demonstrated a neuroprotective potency of unspecific
      group III mGluR agonists in in vitro and in vivo models of excitotoxicity, little
      is known about the protective role of group III mGlu receptor activation against
      neuronal cell injury evoked by ischemic conditions. The aim of the present study
      was to assess neuroprotective potential of the allosteric agonist of mGlu7
      receptor, N,N'-Bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082)
      against oxygen-glucose deprivation (OGD)- and kainate (KA)-evoked neuronal cell
      damage in primary neuronal cultures, with special focus on its efficacy after
      delayed application. We demonstrated that in cortical neuronal cultures exposed
      to a 180 min OGD, AMN082 (0.01-1 uM) in a concentration- and time-dependent way
      attenuated the OGD-induced changes in the LDH release and MTT reduction assays.
      AMN082 (0.5 and 1 uM) produced also neuroprotective effects against KA-evoked
      neurotoxicity both in cortical and hippocampal cultures. Of particular importance
      was the finding that AMN082 attenuated excitotoxic neuronal injury after delayed
      application (30 min after OGD, or 30 min-1 h after KA). In both models of
      neurotoxicity, namely OGD- and KA-induced injury, the neuroprotective effects of
      AMN082 (1 uM) were reversed by the selective mGlu7 antagonist, 6-(4
      Methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridin-4(5H)-one
      hydrochloride (MMPIP, 1 uM), suggesting the mGlu7-dependent mechanism of
      neuroprotective effects of AMN082. Next, we showed that AMN082 (0.5 and 1 uM)
      attenuated the OGD-induced increase in the number of necrotic nuclei as well
      inhibited the OGD-evoked calpain activation, suggesting the participation of
      these processes in the mechanism of AMN082-mediated protection. Additionally, we
      showed that protection evoked by AMN082 (1 uM) in KA model was connected with the
      inhibition of toxin-induced caspase-3 activity, and this effect was abolished by
      the mGlu7 receptor antagonist. The obtained results indicated that the activation
      of mGlu7 receptors may be a promising target for neuroprotection against ischemic
      and excitotoxic insults.

PMID- 25576185
TI  - Factor Structure and Initial Validation of a Multidimensional Measure of
      Difficulties in the Regulation of Positive Emotions: The DERS-Positive.
AB  - Emotion regulation difficulties are a transdiagnostic construct relevant to
      numerous clinical difficulties. Although the Difficulties in Emotion Regulation
      Scale (DERS) is a multidimensional measure of maladaptive ways of responding to
      emotions, it focuses on difficulties with the regulation of negative emotions and
      does not assess emotion dysregulation in the form of problematic responding to
      positive emotions. The aim of this study was to develop and validate a measure of
      clinically relevant difficulties in the regulation of positive emotions (DERS
      Positive). Findings revealed a three-factor structure and supported the internal
      consistency and construct validity of the total and subscale scores. 

PMID- 25576186
TI  - Immunotoxicity in ascidians: antifouling compounds alternative to organotins-IV.
      The case of zinc pyrithione.
AB  - New biocides such as the organometallic compound zinc pyrithione (ZnP) have been
      massively introduced by many countries in formulations of antifouling paints
      following the ban on tributyltin (TBT). The effects of sublethal concentrations
      (LC50=82.5 MUM, i.e., 26.2 mg/l) on cultured haemocytes of the ascidian Botryllus
      schlosseri have been investigated and compared with TBT. The percentage of
      haemocytes with amoeboid morphology and containing phagocytised yeast cells were
      significantly (p<0.05) reduced after exposure to 0.1 (31.7 MUg/l) and 0.5 MUM
      (158 MUg/l), respectively. An antagonistic interaction in inducing cytoskeletal
      alterations was observed when ZnP and TBT were co-present in the exposure medium.
      ZnP affected only the actin component. As caused by TBT, ZnP induced apoptosis
      and inhibited both oxidative phosphorylation and lysosomal activities. In
      contrast to the case of TBT, a decrement in Ca(2+)-ATPase activity and a decrease
      in cytosolic Ca(2+) were detected after incubation at the highest concentration
      (1 MUM, i.e., 317.7 MUg/l) used. In comparison with other antifouling compounds,
      ZnP shows as much toxicity as TBT to cultured haemocytes at extremely low
      concentrations interfering with fundamental cell activities.

PMID- 25576187
TI  - Life stage dependent responses to the lampricide, 3-trifluoromethyl-4-nitrophenol
      (TFM), provide insight into glucose homeostasis and metabolism in the sea lamprey
      (Petromyzon marinus).
AB  - The primary method of sea lamprey (Petromyzon marinus) control in the Great Lakes
      is the treatment of streams and rivers with the pesticide 3-trifluoromethyl-4
      nitrophenol (TFM), which targets larval sea lamprey. However, less is known about
      the effects of TFM on other stages of the sea lamprey's complex life cycle. The
      goal of this study was to determine how TFM affected internal energy stores,
      metabolites, and ion balance in larval, juvenile (parasitic) and adult sea
      lamprey. The larvae were more tolerant to TFM than the adults, with a 2-fold
      higher 12h TFM LC50 and a 1.5-fold higher LC99.9. Acute (3h) exposure of the
      larvae, parasites and adults to their respective 12h TFM LC99.9 led to marked
      reductions in glycogen and phosphocreatine in the adult brain, with lesser or no
      effect in the larvae and parasites. Increased lactate in the brain, at less than
      the expected stoichiometry, suggested that it was exported to the blood. Kidney
      glycogen declined after TFM exposure, suggesting that this organ plays an
      important role in glucose homeostasis. TFM-induced disturbances to ion balance
      were minimal. In conclusion, TFM perturbs energy metabolism in all major stages
      of the sea lamprey life cycle in a similar fashion, but the adults appear to be
      the most sensitive. Thus, the adult stage could be a viable and effective target
      for TFM treatment, particularly when used in combination with other existing and
      emerging strategies of sea lamprey control. 

PMID- 25576188
TI  - OSC2 and CYP716A14v2 catalyze the biosynthesis of triterpenoids for the cuticle
      of aerial organs of Artemisia annua.
AB  - Artemisia annua is widely studied for its ability to accumulate the antimalarial
      sesquiterpenoid artemisinin. In addition to producing a variety of
      sesquiterpenoids, A. annua also accumulates mono-, di-, and triterpenoids, the
      majority of which are produced in the glandular trichomes. A. annua also has
      filamentous trichomes on its aerial parts, but little is known of their
      biosynthesis potential. Here, through a comparative transcriptome analysis
      between glandular and filamentous trichomes, we identified two genes, OSC2 and
      CYP716A14v2, encoding enzymes involved in the biosynthesis of specialized
      triterpenoids in A. annua. By expressing these genes in Saccharomyces cerevisiae
      and Nicotiana benthamiana, we characterized the catalytic function of these
      proteins and could reconstitute the specialized triterpenoid spectrum of A. annua
      in these heterologous hosts. OSC2 is a multifunctional oxidosqualene cyclase that
      produces alpha-amyrin, beta-amyrin, and delta-amyrin. CYP716A14v2 is a P450
      belonging to the functionally diverse CYP716 family and catalyzes the oxidation
      of pentacyclic triterpenes, leading to triterpenes with a carbonyl group at
      position C-3, thereby providing an alternative biosynthesis pathway to 3-oxo
      triterpenes. Together, these enzymes produce specialized triterpenoids that are
      constituents of the wax layer of the cuticle covering the aerial parts of A.
      annua and likely function in the protection of the plant against biotic and
      abiotic stress. 

PMID- 25576189
TI  - Besnoitia besnoiti infection in cattle and mice: ultrastructural pathology in
      acute and chronic besnoitiosis.
AB  - Current knowledge on bovine besnoitiosis, caused by the emerging apicomplexan
      pathogen Besnoitia besnoiti, is still fragmentary. So far, studies dealing with
      ultrastructural pathology focused mainly on the easily accessible chronic stage,
      whereas ultrastructural investigations of tachyzoites were confined to in vitro
      studies. In the study presented here, the ultrastructural pathology of naturally
      B. besnoiti-infected cattle in the acute and chronic disease stages and
      experimentally B. besnoiti-infected mice was monitored. Further, the
      ultrastructure of tachyzoites and bradyzoites was investigated. Skin samples of
      two adult Limousin cows and one adult Limousin bull naturally infected with B.
      besnoiti and liver and skin samples of gamma-interferon knockout mice infected
      with B. besnoiti were examined in semithin sections stained with toluidine blue
      and safranin and in ultrathin sections contrasted with uranyl acetate and lead
      citrate. Samples of vessel walls of the bull and nasal mucosa of one cow were
      examined by scanning electron microscopy. Few tachyzoites-like endozoites were
      detected for the first time in bovine skin, and large numbers of tachyzoites were
      detected in murine skin and liver. Within tissue cysts in bovine skin, numerous
      bradyzoites were observed displaying signs of degeneration. Tachyzoites had
      apicomplexan endozoite ultrastructure. B. besnoiti tachyzoites and bradyzoites
      differed in shape and the number of amylopectin granules. Transmission and
      scanning electron microscopy confirmed the presence of two different cyst wall
      layers, and the present results on cyst wall ultrastructure were in accordance
      with those previously obtained by histological sections. 

PMID- 25576190
TI  - Erratum to: Dujardinascaris gigantea sp. n. (Nematoda: Ascaridida) from the
      critically endangered crocodile Alligator sinensis Fauvel (Reptilia: Crocodylia).

PMID- 25576191
TI  - Depletion of regulatory T cells decreases cardiac parasitosis and inflammation in
      experimental Chagas disease.
AB  - Infection with the protozoan parasite Trypanosoma cruzi may lead to a potentially
      fatal cardiomyopathy known as Chagas heart disease. This disease is characterized
      by infiltration of the myocardium by mononuclear cells, including CD4+ T cells,
      together with edema, myofibrillary destruction, and fibrosis. A multifaceted
      systemic immune response develops that ultimately keeps parasitemia and tissue
      parasitosis low. T helper 1 and other pro-inflammatory T cell responses are
      effective at keeping levels of T. cruzi low in tissues and blood, but they may
      also lead to tissue inflammation when present chronically. The mechanism by which
      the inflammatory response is regulated in T. cruzi-infected individuals is
      complex, and the specific roles that Th17 and T regulatory (Treg) cells may play
      in that regulation are beginning to be elucidated. In this study, we found that
      depletion of Treg cells in T. cruzi-infected mice leads to reduced cardiac
      parasitosis and inflammation, accompanied by an augmented Th1 response early in
      the course of infection. This is followed by a downregulation of the Th1 response
      and increased Th17 response late in infection. The effect of Treg cell depletion
      on the Th1 and Th17 cells is not observed in mice immunized with T. cruzi in
      adjuvant. This suggests that Treg cells specifically regulate Th1 and Th17 cell
      responses during T. cruzi infection and may also be important for modulating
      parasite clearance and inflammation in the myocardium of T. cruzi-infected
      individuals.

PMID- 25576193
TI  - Confirmed enterovirus encephalitis with associated steroid-responsive acute
      disseminated encephalomyelitis: an overlapping infection and inflammation
      syndrome.
AB  - BACKGROUND: Inflammatory disorders of the central nervous system have generally
      been separated into infectious or immune-mediated aetiologies. However, there are
      emerging examples of confirmed infectious viral infection of the brain followed
      by secondary inflammation or autoimmunity that is amenable to immune suppressive
      therapies. METHODS: We report four children with confirmed enterovirus
      encephalitis (CSF enterovirus PCR positivity), who had MRI evidence of
      inflammatory demyelination compatible with ADEM. RESULTS: Two patients had a
      monophasic course, whereas two had a biphasic course. Serum myelin
      oligodendrocyte glycoprotein antibodies were negative in two tested patients,
      although all patients had mirrored CSF and serum oligoclonal bands. All four
      patients only improved with introduction of immune therapy (corticosteroids in
      three, corticosteroid and intravenous immunoglobulin in one). CONCLUSION: These
      cases provide a further example of the overlap between CNS infection and immune
      mediated CNS disease. Randomised controlled trials investigating immune therapies
      in encephalitis are required.

PMID- 25576192
TI  - Novobiocin and peptide analogs of alpha-factor are positive allosteric modulators
      of the yeast G protein-coupled receptor Ste2p.
AB  - G protein-coupled receptors (GPCRs) are the target of many drugs prescribed for
      human medicine and are therefore the subject of intense study. It has been
      recognized that compounds called allosteric modulators can regulate GPCR activity
      by binding to the receptor at sites distinct from, or overlapping with, that
      occupied by the orthosteric ligand. The purpose of this study was to investigate
      the nature of the interaction between putative allosteric modulators and Ste2p, a
      model GPCR expressed in the yeast Saccharomyces cerevisiae that binds the
      tridecapeptide mating pheromone alpha-factor. Biological assays demonstrated that
      an eleven amino acid alpha-factor analog and the antibiotic novobiocin were
      positive allosteric modulators of Ste2p. Both compounds enhanced the biological
      activity of alpha-factor, but did not compete with alpha-factor binding to Ste2p.
      To determine if novobiocin and the 11-mer shared a common allosteric binding
      site, a biologically-active analog of the 11-mer peptide ([Bio-DOPA]11-mer) was
      chemically cross-linked to Ste2p in the presence and absence of novobiocin.
      Immunoblots probing for the Ste2p-[Bio-DOPA]11-mer complex revealed that
      novobiocin markedly decreased cross-linking of the [Bio-DOPA]11-mer to the
      receptor, but cross-linking of the alpha-factor analog [Bio-DOPA]13-mer, which
      interacts with the orthosteric binding site of the receptor, was minimally
      altered. This finding suggests that both novobiocin and [Bio-DOPA]11-mer compete
      for an allosteric binding site on the receptor. These results indicate that Ste2p
      may provide an excellent model system for studying allostery in a GPCR. 

PMID- 25576194
TI  - Avian reovirus S1133-induced apoptosis is associated with Bip/GRP79-mediated Bim
      translocation to the endoplasmic reticulum.
AB  - In this study the mechanism of avian reovirus (ARV) S1133-induced pathogenesis
      was investigated, with a focus on the contribution of ER stress to apoptosis. Our
      results showed that upregulation of the ER stress response protein, as well as
      caspase-3 activation, occurred in ARV S1133-infected cultured cells and in SPF
      White Leghorn chicks organs. Upon infection, Bim was translocated specifically to
      the ER, but not mitochondria, in the middle to late infectious stages. In
      addition, ARV S1133 induced JNK phosphorylation and promoted JNK-Bim complex
      formation, which correlated with the Bim translocation and apoptosis induction
      that was observed at the same time point. Knockdown of BiP/GRP78 by siRNA and
      inhibition of BiP/GRP78 using EGCG both abolished the formation of the JNK-Bim
      complex, caspase-3 activation, and subsequent apoptosis induction by ARV S1133
      efficiently. These results suggest that BiP/GRP78 played critical roles and works
      upstream of JNK-Bim in response to the ARV S1133-mediated apoptosis process. 

PMID- 25576195
TI  - 17beta-estradiol protects against apoptosis induced by interleukin-1beta in rat
      nucleus pulposus cells by down-regulating MMP-3 and MMP-13.
AB  - In our previous study, 17beta-estradiol was proved to protect rat annulus
      fibrosus cells against apoptosis induced by interleukin-1beta (IL-1beta).
      However, whether 17beta-estradiol has protective effect on rat nucleus pulposus
      cells remains unclear. The purpose of this study was to further explore the
      effects of 17beta-estradiol on rat nucleus pulposus cells based on IL-1beta
      induced apoptosis. TUNEL assay and Annexin V/PI double staining were used to
      detect apoptosis and revealed that IL-1beta induced notable apoptosis, which was
      reversed by 17beta-estradiol. Meanwhile, cell viability and binding ability were
      decreased by IL-1beta, but activated caspase-3 was increased. However, all of the
      detected effects of IL-1beta were eliminated by 17beta-estradiol. Furthermore,
      real-time quantitative RT-PCR was used to further find that IL-1beta
      downregulated expression level of type II collagen, aggrecan, tissue inhibitor of
      matrix metalloproteinase (TIMP)-1, while upregulated matrix metalloproteinase
      (MMP)-3, MMP-13 and Bcl-2, which was further confirmed by western blot. Finally,
      17beta-estradiol was proved to abolish the above negative effects of IL-1beta. In
      summary, this work presented that IL-1beta maybe induced apoptosis of rat nucleus
      pulposus cells, which was resisted by 17beta-estradiol by down-regulating MMP-3
      and MMP-13 via a mitochondrial pathway. This research provides a novel insight
      into the anti-apoptotic effect of 17beta-estradiol on IL-1beta-induced
      cytotoxicity, and may potentially lead to a better understanding of the clinical
      effects of 17beta-estradiol, especially in terms of intervertebral disc
      degeneration. 

PMID- 25576196
TI  - Application of a two-stage fuzzy neural network to a prostate cancer prognosis
      system.
AB  - OBJECTIVE: This study intends to develop a two-stage fuzzy neural network (FNN)
      for prognoses of prostate cancer. METHODS: Due to the difficulty of making
      prognoses of prostate cancer, this study proposes a two-stage FNN for prediction.
      The initial membership function parameters of FNN are determined by cluster
      analysis. Then, an integration of the optimization version of an artificial
      immune network (Opt-aiNET) and a particle swarm optimization (PSO) algorithm is
      developed to investigate the relationship between the inputs and outputs.
      RESULTS: The evaluation results for three benchmark functions show that the
      proposed two-stage FNN has better performance than the other algorithms. In
      addition, model evaluation results indicate that the proposed algorithm really
      can predict prognoses of prostate cancer more accurately. CONCLUSIONS: The
      proposed two-stage FNN is able to learn the relationship between the clinical
      features and the prognosis of prostate cancer. Once the clinical data are known,
      the prognosis of prostate cancer patient can be predicted. Furthermore, unlike
      artificial neural networks, it is much easier to interpret the training results
      of the proposed network since they are in the form of fuzzy IF-THEN rules. These
      rules are very important for medical doctors. This can dramatically assist
      medical doctors to make decisions.

PMID- 25576197
TI  - Therapeutic potential of peroxynitrite decomposition catalysts: a patent review.
AB  - INTRODUCTION: Peroxynitrite is a cytotoxic oxidant species implicated in a host
      of pathologies, including inflammatory and neurodegenerative diseases, cancer,
      radiation injury and chronic pain. With the recognition of the role of
      peroxynitrite in disease, numerous experimental and therapeutic tools have arisen
      to probe peroxyntirite's pathophysiological contribution and attenuate its
      oxidative damage. Peroxynitrite decomposition catalysts (PNDCs) are redox-active
      compounds that detoxify peroxynitrite by catalyzing its isomerization or
      reduction to nitrate or nitrite. AREAS COVERED: This review discusses recent
      research articles and patents published 1995 - 2014 on the development and
      therapeutic use of PNDCs. Iron and manganese metalloporphyrin PNDCs attenuate the
      toxic effects of peroxynitrite and are currently being developed for clinical
      applications. Additionally, some Mn porphyrin-based PNDCs have optimized
      pharmaceutical properties such that they exhibit greater peroxynitrite
      selectivity. Other classes of PNDC agents, including
      bis(hydroxyphenyl)dipyrromethenes and metallocorroles, have demonstrated
      preclinical efficacy, oral availability and reduced toxicity risk. EXPERT
      OPINION: Interest in the drug-like properties of peroxynitrite-neutralizing
      agents has grown with the realization that PNDCs will be powerful tools in the
      treatment of disease. The design of compounds with enhanced oral availability and
      peroxynitrite selectivity is a critical step toward the availability of safe,
      effective and selective redox modulators for the treatment of peroxynitrite
      associated pathologies.

PMID- 25576198
TI  - Effects of activated carbon characteristics on the electrosorption capacity of
      titanium dioxide/activated carbon composite electrode materials prepared by a
      microwave-assisted ionothermal synthesis method.
AB  - Titanium dioxide (TiO2)/ activated carbon (AC) composite materials, as capacitive
      deionization electrodes, were prepared by a two-step microwave-assisted
      ionothermal synthesis method. The electrosorption capacity of the composite
      electrodes was studied and the effects of AC characteristics were explored. These
      effects were investigated by multiple analytical techniques, including X-ray
      photoelectron spectroscopy, thermogravimetry analysis and electrochemical
      impedance spectroscopy, etc. The experimental results indicated that the
      electrosorption capacity of the TiO2/AC composite electrode is dependent on the
      characteristics of AC including the pore structure and the surface property. An
      enhancement in electrosorption capacity was observed for the TiO2/AC composite
      electrode prepared from the AC with higher mesopore content and less hydrophilic
      surface. This enhancement is due to the deposition of anatase TiO2 with suitable
      amount of Ti-OH. On the other hand, a decline in electrosorption capacity was
      observed for the TiO2/AC composite electrode prepared from the AC with higher
      micropore content and highly hydrophilic surface. High content of hydrogen bond
      complex formed between the functional group on hydrophilic surface with H2O,
      which will slow down the TiO2 precursor-H2O reaction. In such situation, the
      effect of TiO2 becomes unfavorable as the loading amount of TiO2 is less and the
      micropore can also be blocked. 

PMID- 25576199
TI  - Developing the surveillance algorithm for detection of failure to recognize and
      treat severe sepsis.
AB  - OBJECTIVE: To develop and test an automated surveillance algorithm (sepsis
      "sniffer") for the detection of severe sepsis and monitoring failure to recognize
      and treat severe sepsis in a timely manner. PATIENTS AND METHODS: We conducted an
      observational diagnostic performance study using independent derivation and
      validation cohorts from an electronic medical record database of the medical
      intensive care unit (ICU) of a tertiary referral center. All patients aged 18
      years and older who were admitted to the medical ICU from January 1 through March
      31, 2013 (N=587), were included. The criterion standard for severe sepsis/septic
      shock was manual review by 2 trained reviewers with a third superreviewer for
      cases of interobserver disagreement. Critical appraisal of false-positive and
      false-negative alerts, along with recursive data partitioning, was performed for
      algorithm optimization. RESULTS: An algorithm based on criteria for suspicion of
      infection, systemic inflammatory response syndrome, organ hypoperfusion and
      dysfunction, and shock had a sensitivity of 80% and a specificity of 96% when
      applied to the validation cohort. In order, low systolic blood pressure, systemic
      inflammatory response syndrome positivity, and suspicion of infection were
      determined through recursive data partitioning to be of greatest predictive
      value. Lastly, 117 alert-positive patients (68% of the 171 patients with severe
      sepsis) had a delay in recognition and treatment, defined as no lactate and
      central venous pressure measurement within 2 hours of the alert. CONCLUSION: The
      optimized sniffer accurately identified patients with severe sepsis that bedside
      clinicians failed to recognize and treat in a timely manner.

PMID- 25576200
TI  - Influence of apical root resection on the biomechanical response of a single
      rooted tooth-part 2: apical root resection combined with periodontal bone loss.
AB  - INTRODUCTION: In a clinical situation, an apically resected tooth is often
      accompanied by a varying degree of periodontal bone loss. The purpose of this
      study was to assess the influence of apical root resection combined with
      periodontal bone loss on the biomechanical response of a single-rooted tooth.
      METHODS: A basic intact model and a basic apically resected model of the upper
      central incisor were selected for the numerical analysis. From each basic model,
      6 models were developed assuming different amounts of periodontal bone loss (0,
      0.5, 1, 1.5, 2, and 3 mm). Maximum von Mises stress (sigma max), maximum tooth
      displacement (DeltaR max), and effective crown-to-root ratio (alpha) were
      calculated for each condition. RESULTS: There were only marginal differences (a
      2.1% difference in sigma max and a 16.9% difference in DeltaR max) between the
      biomechanical responses of the intact model and the apically resected model when
      the tooth was supported by a normal periodontium. However, when destruction of
      the periodontium was assumed, the intact model and the apically resected model
      responded differently. The difference increased as the periodontal bone loss
      progressed, resulting in a 68.7% difference in sigma max and a 56.3% difference
      in DeltaR max when the periodontal bone loss increased to 3 mm (alpha = 0.48).
      CONCLUSIONS: Although the biomechanical response of an apically resected tooth
      was relatively stable when the tooth was supported by a normal periodontium, the
      apically resected tooth showed a more deteriorated response compared with the
      intact tooth as the periodontal bone loss progressed.

PMID- 25576201
TI  - Periapical cytokine expression in sickle cell disease.
AB  - INTRODUCTION: Sickle cell anemia (SCA) is the most prevalent genetic disease
      worldwide. Patients with SCA exhibit increased levels of proinflammatory
      mediators as part of a permanently activated immunoinflammatory status. METHODS:
      The aim of this study was to evaluate the mRNA expression levels of the cytokines
      interferon (IFN-gamma), tumor necrosis factor, interleukin (IL-1beta, IL-17A, IL
      10), receptor activator for nuclear factor kappa B ligand, and the chemokines
      CCL2/MCP-1 and CCL5 in the periapical interstitial fluid from SCA individuals
      compared with healthy individuals. Samples were collected from 12 teeth of SCA
      patients and 12 non-SCA patients with apical periodontitis. In addition, 12 teeth
      were sampled from the periapical region of healthy patients with vital pulp
      (control). The expression of cytokine mRNA was detected by using real-time
      polymerase chain reaction. RESULTS: The expression of mRNA for the Th1-associated
      cytokines IFN-gamma, tumor necrosis factor-alpha, and IL-1beta were significantly
      higher in SCA individuals than in the control individuals (P < .05). Among Th1
      associated cytokines, only IFN-gamma was significantly increased in non-SCA
      compared with control patients (vital pulp). The expression of IL-17A mRNA was
      significant higher in SCA cases than in control samples (P < .05), whereas the IL
      10 mRNA expression was significantly increased in SCA and non-SCA individuals
      when compared with the control group. Similar levels of receptor activator for
      nuclear factor kappa B ligand, CCL2, and CCL5 mRNA expression were observed in
      all samples. However, no significant differences were observed in the expression
      of cytokine or chemokine mRNA between SCA and non-SCA individuals (P > .05).
      CONCLUSIONS: The results were able to demonstrate that SCA patients presented
      prone proinflammatory ability, despite the fact that any differences in
      periapical immune responses between SCA and non-SCA individuals were not
      observed.

PMID- 25576202
TI  - The effect of obturation technique on the push-out bond strength of calcium
      silicate sealers.
AB  - INTRODUCTION: Calcium silicate-based sealers are known to have excellent sealing
      ability and bioactivities. They are typically recommended to be used in a single
      cone (SC) technique. No studies have evaluated the effects of the thermoplastic
      obturation technique on the dentin interface of these sealers. The purpose of
      this study was to evaluate the push-out bond strengths of MTA Plus Sealer (Avalon
      Biomed Inc, Bradenton, FL) and EndoSequence BC Sealer (BC; Brasseler USA,
      Savannah, GA) when they were used in a thermoplastic technique. METHODS: Fifty
      single-rooted human extracted teeth were randomly divided into 5 groups (n = 10),
      instrumented, and obturated with the SC technique or continuous wave (CW)
      technique: group 1, BC-SC; group 2, BC-CW; group 3, MTA Plus-SC; group 4, MTA
      Plus-CW; and group 5, AH Plus (Dentsply DeTrey, Konstanz, Germany)-CW. The roots
      were sectioned into 1.0-mm-thick slices, and bond strengths were measured using a
      standardized push-out test. The mode of failure was determined by visual
      inspection under magnification. RESULTS: The MTA Plus-CW had statistically
      significant lower bond strengths than all other groups. The BC-SC group had
      statistically higher bond strengths than the MTA Plus-SC and AH Plus-CW groups.
      No significant differences were seen among the other groups. Modes of failure
      were predominately cohesive or mixed except for group 4 (ie, MTA Plus-CW) in
      which nearly half the specimens had no visible sealer. CONCLUSIONS: BC and MTA
      Plus sealer showed favorable bond strengths when used in an SC technique. The CW
      obturation technique decreased the bond strengths of these sealers.

PMID- 25576203
TI  - Color stabilities of calcium silicate-based materials in contact with different
      irrigation solutions.
AB  - INTRODUCTION: Mineral trioxide aggregate (MTA) has been reported to cause tooth
      discoloration when applied in the esthetic zone. A previous study has shown
      discoloration of MTA in contact with root canal irrigation solutions. Moreover,
      there are limited data on color stability of novel calcium silicate-based
      materials. This study aimed to evaluate color changes of 4 calcium silicate-based
      materials in contact with different irrigation solutions. METHODS: ProRoot white
      MTA (Dentsply Tulsa Dental, Johnson City, TN), white MTA Angelus (Angelus
      Solucoes Odontologicas, Londrina, Brazil), Biodentine (Septodont, Saint Maur des
      Fosses, France), and BioAggregate (Innovative Bioceramix, Vancouver, BC, Canada)
      samples were assessed. Materials were mixed according to the manufacturers'
      instructions. Cylindric samples (10-mm diameter and 2-mm height) were obtained by
      curing in molds for each material's setting time at 100% humidity and 37 degrees
      C. Each specimen was immersed in 5% sodium hypochlorite, 2% chlorhexidine
      gluconate, or distilled water for 24 hours. Color changes were measured with a
      spectrophotometer. Data were analyzed by using 2-way analysis of variance and
      post hoc Bonferroni tests. RESULTS: All materials exhibited clinically
      perceptible discoloration when immersed in sodium hypochlorite and chlorhexidine
      gluconate. ProRoot white MTA showed a statistically significant difference from
      Bioaggregate, Biodentine, and white MTA Angelus. Distilled water did not cause
      clinically perceptible discoloration of any material. CONCLUSIONS: In
      esthetically critical regions, compounds free of bismuth oxide, Biodentine, and
      BioAggregate can be considered as alternatives to MTA. However, all calcium
      silicate-based materials exhibited clinically perceptible color changes.

PMID- 25576204
TI  - Treatment of large apical lesions with mucosal fenestration: a clinical study
      with long-term evaluation.
AB  - INTRODUCTION: Mucosal fenestration at the root apex may compromise the treatment
      results of periradicular surgery from exposing the surgical wound to the oral
      environment. The purpose of this study was to evaluate the long-term outcomes of
      periapical lesions with mucosal fenestrations treated by guided tissue
      regeneration (GTR) combined with the management of soft tissue defects. METHODS:
      Five patients with mucosal fenestration and large periapical lesions were treated
      by endodontic surgeries and periodontal regenerative procedures during 1999 to
      2006. The barrier membranes and osseous grafts were placed over the periapical
      defects after root end resection and retrograde filling. The mucosal openings in
      all cases were sutured, whereas a connective tissue graft was placed before
      repositioning the flap in 2 cases. RESULTS: The cases involving connective tissue
      grafting showed complete soft tissue coverage, whereas 2 of the 3 cases involving
      primary closure of fenestrations still had a small soft tissue opening that was
      further managed by placement of a connective tissue graft beneath in 1 case and
      direct suturing in the other case. After at least 6 years (72-160 months) of
      follow-up, all cases showed complete soft tissue and radiographic healing.
      CONCLUSIONS: Connective tissue grafting in combination with GTR therapy
      facilitated fenestration closure and ensured long-term success in the treatment
      of a large periapical bony defect with mucosal fenestration.

PMID- 25576205
TI  - The effect of using RC prep during root canal preparation on the incidence of
      dentinal defects.
AB  - INTRODUCTION: The purpose of this in vitro study was to evaluate the effect of
      using RC Prep (Well-Prep, Vericom Co, Anyang, Korea) during root canal
      preparation on the incidence of defects in root canal walls. METHODS: One hundred
      extracted mandibular incisors with single canals were randomly divided into 1
      control group and 4 experimental groups (n = 20). The teeth in group 1 (control)
      were coronally flared with Gates Glidden drills (Mani, Japan), but no further
      preparation was made. All teeth in the experimental groups were first coronally
      flared with Gates Glidden drills and then prepared similarly by means of ProTaper
      instruments (Dentsply Maillefer, Ballaigues, Switzerland). The difference between
      the experimental groups was the following: in group 2, saline was used as an
      irrigation solution without the application of RC Prep; in group 3, teeth were
      irrigated with saline, and RC Prep was also applied to canals before the
      insertion of each file; in group 4, sodium hypochlorite (NaOCl) was used for
      irrigation without the application of RC Prep; and in group 5, both NaOCl and RC
      Prep were used. The apical root surface and horizontal sections 3, 6, and 9 mm
      from the apex were observed under a microscope. The presence of cracks was noted.
      The chi-square test and Fisher exact test were used for statistical analysis of
      differences between and among the groups. RESULTS: A significant difference was
      found between and among the 5 groups (P < .05). Group 4 (NaOCl), which had the
      highest number of cracked teeth, was significantly different from group 1
      (control) (P < .05). RC Prep, with both saline and NaOCl, had no significant
      effect on the incidence of microcrack formation (P > .05). When data were pooled,
      regardless of whether RC Prep was used, there was a significant difference
      between saline (groups 2 + 3) and NaOCl (groups 4 + 5) (P < .05). CONCLUSIONS: RC
      Prep was unable to reduce the risk of dentinal defects. NaOCl caused more defects
      compared with saline.

PMID- 25576206
TI  - Shaping ability of 4 different single-file systems in simulated S-shaped canals.
AB  - INTRODUCTION: The aim of this study was to compare the shaping ability of 4
      different single-file systems in simulated S-shaped canals. METHODS: Sixty-four S
      shaped canals in resin blocks were prepared to an apical size of 25 using
      Reciproc (VDW, Munich, Germany), WaveOne (Dentsply Maillefer, Ballaigues,
      Switzerland), OneShape (Micro Mega, Besancon, France), and F360 (Komet Brasseler,
      Lemgo, Germany) (n = 16 canals/group) systems. Composite images were made from
      the superimposition of pre- and postinstrumentation images. The amount of resin
      removed by each system was measured by using a digital template and image
      analysis software. Canal aberrations and the preparation time were also recorded.
      The data were statistically analyzed by using analysis of variance, Tukey, and
      chi-square tests. RESULTS: Canals prepared with the F360 and OneShape systems
      were better centered compared with the Reciproc and WaveOne systems. Reciproc and
      WaveOne files removed significantly greater amounts of resin from the inner side
      of both curvatures (P < .05). Instrumentation with OneShape and Reciproc files
      was significantly faster compared with WaveOne and F360 files (P < .05). No
      instrument fractured during canal preparation. CONCLUSIONS: Under the conditions
      of this study, all single-file instruments were safe to use and were able to
      prepare the canals efficiently. However, single-file systems that are less
      tapered seem to be more favorable when preparing S-shaped canals.

PMID- 25576207
TI  - Effect of varying water-to-powder ratios and ultrasonic placement on the
      compressive strength of mineral trioxide aggregate.
AB  - INTRODUCTION: The purpose of this study was to compare the compressive strength
      of mineral trioxide aggregate (MTA) when mixed with 2 different water-to-powder
      (WP) proportions using either hand or ultrasonic placement. METHODS: Tooth
      colored ProRoot MTA (Dentsply Maillefer, Ballaigues, Switzerland) and white MTA
      Angelus (Angelus Solucoes Odontologicas, Londrina, Brazil) were investigated. One
      gram of each MTA powder was mixed with either 0.34 or 0.40 g distilled water. The
      4 groups were further divided into 2 groups of 5 specimens for each of the
      following techniques: conventional (ie, hand placement) and placement using
      indirect ultrasonic activation for 30 seconds. All specimens were subjected to
      compressive strength testing after 4 days. The results were statistically
      analyzed with multivariate analysis of variance and Tukey Honestly Significant
      Difference tests at a significance level of P < .05. RESULTS: The mean
      compressive strength values of ProRoot MTA (84.17 +/- 22.68) were significantly
      greater than those of MTA Angelus (47.71 +/- 14.29) (P < .01). Specimens mixed
      with the 0.34 WP ratio had higher compressive strength values (72.85 +/- 25.77)
      than those mixed with the 0.40 WP ratio (56.69 +/- 24.85) (P < .05). The highest
      compressive strength values were recorded for ProRoot MTA specimens that were
      mixed in the 0.34 WP ratio, and then the samples were placed with ultrasonic
      activation (mean = 91.35 MPa). The lowest values were recorded for MTA Angelus
      samples that were mixed in the 0.40 WP ratio, and the specimens were placed
      without ultrasonic activation (mean = 36.36 MPa). Ultrasonic activation had no
      significant difference in terms of compressive strength. CONCLUSIONS: When using
      ProRoot MTA and MTA Angelus, higher WP ratios resulted in lower compressive
      strength values. Ultrasonication had no significant effect on the compressive
      strength of the material regardless of the WP ratio that was used. Therefore,
      adherence to the manufacturer's recommended WP ratio when preparing MTA for use
      in dental applications is advised.

PMID- 25576208
TI  - Rapid method for the detection of root canal bacteria in endodontic therapy.
AB  - INTRODUCTION: Complete eradication of microorganisms is essential for successful
      root canal therapy. However, current methods to evaluate persistent bacteria
      after therapy are not widely practiced. Adenosine triphosphate (ATP) is an
      indicator of viable cells. The bioluminescence-based ATP assay is easy to
      perform, and results can be obtained in a clinically relevant time frame of 5
      minutes. The aims of this study were to evaluate the sensitivity of the ATP
      detection method and the specificity of this assay for viable cells and to
      compare the ATP and culture methods from root canal samples of patients
      undergoing endodontic treatment. METHODS: The sensitivity of the ATP assay was
      determined using bacterial species commonly isolated from root canals. Bacteria
      were treated with sodium hypochlorite; after which, culture plating and the ATP
      assay were performed. Forty-three root canal samples before (S1) and after (S2)
      instrumentation and 36 samples after the removal of calcium hydroxide dressing
      (S3) were collected from patients undergoing root canal treatment and subjected
      to ATP assay and anaerobic culture. RESULTS: The sensitivity of the ATP assay was
      determined to be between 10 and 100 bacterial cells. This method of detection
      also correlated well with the presence of viable bacteria. The ATP readings
      obtained allowed clear segregation of anaerobic culture-positive and -negative
      samples obtained from infected root canals of patients. CONCLUSIONS: The ATP
      detection method can be used as a rapid tool to determine the presence of viable
      bacteria during root canal therapy. This method may be potentially useful as an
      adjunct to root canal treatment.

PMID- 25576209
TI  - Effect of raloxifene on periapical lesions in ovariectomized rats.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of raloxifene
      (RLX) during progression of periapical lesions in ovariectomized (OVX) rats.
      METHODS: Female Wistar rats were OVX or subjected to sham surgery and received
      vehicle or RLX by gavage for 90 days. The treatment groups were as follows: sham
      surgery and treated with vehicle (SHAM-veh), OVX and treated with vehicle (OVX
      veh), and OVX and treated with RLX (OVX-RLX). During treatment, the pulp of lower
      first molar was exposed to the oral environment for induction of periapical
      lesion that was analyzed 7 or 30 days after procedure. Blood samples were taken
      from jugular vein for measurement of estradiol, and the mandibles were removed
      and prepared for radiographic, histopathologic, histometric, and
      immunohistochemical analysis. RESULTS: Estradiol plasma concentration showed
      hypoestrogenism in OVX rats. The histopathologic analysis of the OVX/RLX group
      was similar to that of the SHAM-veh group, whereas OVX-veh group showed larger
      periapical lesions with more intense inflammatory response and more cells
      positive for tartrate-resistant acid phosphatase. Radiographically, the groups
      were similar, but lesions on day 7 were smaller than lesions on day 30.
      CONCLUSIONS: The results suggest that hypoestrogenism potentiates the progression
      of periapical lesions, and such condition was reversed by treatment with RLX.

PMID- 25576210
TI  - Association between chronic apical periodontitis and low-birth-weight preterm
      births.
AB  - INTRODUCTION: The objective of this study was to investigate the association
      between chronic apical periodontitis (CAP) and low-birth-weight preterm births
      (LBWPB). METHODS: Sixty-three women in postpartum period were included in this
      case-control study. The case group consisted of mothers of LBWPB infants (n =
      33), and the control group was represented by mothers of newborns at term (n =
      30). The CAP diagnosis was performed by using periapical radiographs through the
      periapical index in postpartum period. The chi(2) test, Fisher exact test, and
      linear and logistic regression were used for statistical analysis. RESULTS: It
      was observed that CAP was present in 54.5% of mothers in the case group and 20.0%
      in the control group (P = .004); postpartum women with CAP had about 3.5 times
      greater odds of LBWPB newborns than women without CAP (adjusted odds ratio, 3.52;
      95% confidence interval, 1.01-12.32). Postpartum women who reported 6 or more
      prenatal consultations reduced odds of LBWPB newborns in 80% (adjusted odds
      ratio, 0.20; 95% CI, 0.06-0.69). It can be estimated that the increase of 1 unit
      of periapical index had a significant association with the reduction of 11/2
      gestational weeks in the crude analysis (beta = -1.5, P = .010) and the reduction
      of 211 g in birth weight after the adjusted analysis (beta = -211, P = .058).
      CONCLUSIONS: Prematurity and low birth weight were associated with
      radiographically detected CAP. Women with CAP in postpartum period had greater
      odds of LBWPB.

PMID- 25576211
TI  - CD44-SLC1A2 fusion transcripts in primary colorectal cancer.
AB  - A CD44-SLC1A2 fusion has recently been discovered in a subset of primary gastric
      cancers, and an APIP-SLC1A2 fusion has been described in a colon cancer cell line
      (SNU-C1); however, whether such SLC1A2 fusions occur in primary colorectal cancer
      (CRC) and whether such fusions are specific for gastrointestinal cancers remain
      uncertain. In the present study, we examined 90 primary CRCs and 112 primary non
      small cell lung cancers (NSCLCs) for CD44-SLC1A2 and APIP-SLC1A2 fusion
      transcripts using RT-PCR and subsequent sequencing analyses. Although the
      expression of both types of SLC1A2 fusion transcripts was not detected in any of
      the NSCLCs, the expression of CD44-SLC1A2, but not the APIP-SLC1A2 fusion
      transcript, was detected in one (1.1 %) CRC. The CD44-SLC1A2 fusion transcript
      was expressed in cancerous tissue but not in corresponding non-cancerous tissue,
      and the fusion occurred between exon 1 of CD44 and exon 2 of SLC1A2; it was
      expected that a slightly truncated but functional SLC1A2 protein would be
      produced under the CD44 promoter. A quantitative RT-PCR analysis revealed that
      SLC1A2 mRNA expression was upregulated in CRC containing SLC1A2 fusion
      transcripts, while it was downregulated in most other CRCs. The SLC1A2 fusion
      positive carcinoma was located on the right-side of colon, was a mucinous
      adenocarcinoma, was immunohistochemically negative for MSH2 mismatch repair
      protein, and contained no APC or KRAS mutations. Together, these results suggest
      that the expression of SLC1A2 fusion transcripts is related to a subset of
      primary CRCs and may contribute to the elucidation of the characteristics of
      SLC1A2 fusion-positive CRCs in the future.

PMID- 25576212
TI  - Thyroid cancer in Egypt: histopathological criteria, correlation with survival
      and oestrogen receptor protein expression.
AB  - Thyroid cancer represents approximately 1% of new cancer and oestrogen may play a
      role in the pathogenesis of thyroid neoplasm. We aimed to study the
      clinicopathological criteria and ER expression of thyroid cancer in Mansoura
      University (Egypt), and to correlate the survival to these clinicopathological
      data and ER expression. This retrospective study reviewed 644 patients with
      histologically proven thyroid carcinoma during the period from 2003 to 2011. 152
      cases during the period between 2008 and 2011 were retrieved from the archive and
      examined by immunohistochemistry for oestrogen receptor-alpha (ER) expression. ER
      alpha expression is significantly associated with the female sex, lymph node
      metastasis, TNM stage, extrathyroid extension, multifocality disease and
      recurrence and in the whole series (p < 0.5). The same was noticed in papillary
      carcinoma (PTC) except the gender of the patient. Tumour type, extrathyroid
      extension and ER expression were the independent prognostic factors of DFS, while
      in PTC, only ER expression was the independent one. The histological type was the
      only independent prognostic factor for OAS in the series were studied for ER
      expression, while extrathyroid extension was the only one that affected OAS of
      PTC. There was significant positive correlation with lymph node metastasis and ER
      expression in whole patient and PTC cases. No difference in survival between the
      low and high ranges of positive oestrogen expression. The prognosis of thyroid
      carcinoma in Egypt is similar to that occurs worldwide. ER-alpha expression was a
      significant prognostic marker for DFS in thyroid cancer and can be used as a
      predictive factor of lymph node metastasis.

PMID- 25576213
TI  - A meta-analysis of body mass index of adolescent and adult survivors of pediatric
      acute lymphoblastic leukemia.
AB  - PURPOSE: We conducted a meta-analysis of existing studies to examine body mass
      index (BMI) of adolescent and adult survivors of pediatric acute lymphoblastic
      leukemia (ALL) compared to individuals without cancer. METHODS: Studies were
      identified and reviewed using specific inclusion criteria. The effect size was
      odds ratio (OR) of the prevalence of overweight/obese BMI (>= 25 kg/m(2)) in ALL
      survivors versus comparison groups. Study data were coded and validated. Fixed
      effects (FE) and random-effects (RE) estimates of the effect size were estimated.
      RESULTS: A total of 9 studies met our inclusion criteria. Survivors were more
      likely to be overweight/obese compared to comparison groups (FE OR = 1.12, 95% CI
      1.06-1.18 and RE OR = 1.28, 95% CI 1.07-1.53). When limited to studies from North
      American samples, female survivors were overweight/obese more often than the
      comparison groups (FE OR = 1.30, 95% CI 1.19-1.43). CONCLUSIONS: Adolescent and
      adult survivors of pediatric ALL, especially female survivors, may be at a higher
      risk of being overweight/obese compared to individuals without cancer. However,
      few studies provided detailed information on patient and treatment factors (e.g.,
      cranial radiation) that can impact BMI. Standardized reporting of study content
      is vital for providing robust information on the risk of developing late effects
      among cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Adolescent and adult
      survivors of pediatric ALL require additional weight management resources such as
      targeted counseling for physical activity and dietician support both early in
      treatment and after the end of their therapy. Female survivors may need
      additional guidance to develop healthy eating practices and to participate in
      exercise programs.

PMID- 25576214
TI  - Contextual factors influencing health-related quality of life in African American
      and Latina breast cancer survivors.
AB  - PURPOSE: This study explored the relationships between systemic- and individual
      level contextual factors and health-related quality of life (HRQOL) in a cohort
      of African American and Latina breast cancer survivors (BCS). METHODS: Baseline
      questionnaire data of 320 BCS who participated in a HRQOL psycho-educational
      intervention were abstracted from the parent study. Hierarchical regression
      analysis tested the independent effects of contextual factors on HRQOL. RESULTS:
      HRQOL was higher in BCS who: were diagnosed at < stage 2 (b = -1.38, p < 0.05),
      expressed satisfaction with their health care (b = 0.20, p < 0.001), had fewer
      comorbidities (b = - 0.60, p < 0.001) and depressive symptoms (b = -0.30, p <
      0.001), and practiced healthy diet and exercise habits (b = 0.02, p < 0.05).
      Demographic and cancer-related factors accounted for 14 % of the variance in
      HRQOL (F[6, 274] = 7.25, p < 0.001). The socio-cultural context (i.e., ethnicity,
      life stress, perceived social support) explained 20 % of the variance in HRQOL
      (FDelta[3, 271] = 27.32, p < 0.001). The health care system context contributed
      an additional 8 % to explaining HRQOL (FDelta[1, 270] = 34.88, p < 0.001). Health
      status and behavioral factors accounted for 18 % of the variance (FDelta[4, 266]
      = 29.55, p < 0.001). The full model explained 59 % of the variance in HRQOL
      (F[14, 266] = 27.76, p < 0.001). CONCLUSIONS: HRQOL in ethnic minority BCS is
      multifaceted and is significantly influenced by cancer-related, socio-cultural,
      health care system, health status, and behavioral contextual factors. Therefore,
      survivorship research and practice must address broad multi-level domains to
      achieve equitable and optimal breast cancer outcomes. IMPLICATIONS FOR CANCER
      SURVIVORS: To enhance HRQOL, survivors must be provided the know-how and support
      to maintain healthy lifestyle and self-management practices. Advocates must
      engage the care team to consider systemic factors, including life stress and
      community resources, to be more patient-centered.

PMID- 25576215
TI  - Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll
      like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis
      B vaccine in patients with chronic kidney disease and type 2 diabetes mellitus.
AB  - BACKGROUND: Many patients with chronic kidney disease (CKD) are hyporesponsive to
      currently licensed alum-adjuvanted hepatitis B vaccines, including Engerix-B((r))
      (HBsAg-Eng). Seroprotection rates (SPRs) are further reduced in CKD patients with
      diabetes mellitus. Three doses of an investigational hepatitis B vaccine (HBsAg
      1018) that uses a Toll-like receptor 9 agonist demonstrated superior SPRs to 4
      double doses of HBsAg-Eng in a large phase 3 trial of CKD patients. METHODS: A
      prespecified subgroup analysis of immunogenicity was conducted in CKD
      participants with type 2 diabetes in the phase 3 trial. RESULTS: In 328
      participants, the peak SPR in the HBsAg-1018 group met criteria for
      noninferiority and superiority to the peak SPR in the HBsAg-Eng group. The peak
      geometric mean concentration of antibody against hepatitis B surface antigen in
      the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng
      group. CONCLUSION: HBsAg-1018 induced significantly higher seroprotection than
      HBsAg-Eng in CKD patients with diabetes.

PMID- 25576216
TI  - Poly-(lactic-co-glycolic-acid)-based particulate vaccines: particle uptake by
      dendritic cells is a key parameter for immune activation.
AB  - Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as
      biodegradable delivery system to improve the potency and safety of protein-based
      vaccines. In this study we analyzed how the size of PLGA particles, and hence
      their ability to be engulfed by dendritic cells (DC), affects the type and
      magnitude of the immune response in comparison to sustained release from a local
      depot. PLGA microparticles (MP, volume mean diameter~112 MUm) and nanoparticles
      (NP, Z-average diameter~350 nm) co-encapsulating ovalbumin (OVA) and poly(I:C),
      with comparable antigen (Ag) release characteristics, were prepared and
      characterized. The immunogenicity of these two distinct particulate vaccines was
      evaluated in vitro and in vivo. NP were efficiently taken up by DC and greatly
      facilitated MHC I Ag presentation in vitro, whereas DC cultured in the presence
      of MP failed to internalize significant amounts of Ag and hardly showed MHC I Ag
      presentation. Vaccination of mice with NP resulted in significantly better
      priming of Ag-specific CD8(+) T cells compared to MP and OVA emulsified with
      incomplete Freund's adjuvant (IFA). Moreover, NP induced a balanced TH1/TH2-type
      antibody response, compared to vaccinations with IFA which stimulated a
      predominant TH2-type response, whereas MP failed to increase antibody titers. In
      conclusion, we postulate that particle internalization is of crucial importance
      and therefore particulate vaccines should be formulated in the nano- but not
      micro-size range to achieve efficient uptake, significant MHC class I cross
      presentation and effective T and B cell responses.

PMID- 25576217
TI  - Association of body mass index with embryonic aneuploidy.
AB  - OBJECTIVE: To determine whether an association exists between body mass index
      (BMI) and embryo ploidy in patients undergoing in vitro fertilization (IVF) with
      trophectoderm biopsy and 24-chromosome preimplantation genetic screening (PGS).
      DESIGN: Retrospective cohort study. SETTING: University-based fertility center.
      PATIENT(S): 279 women aged 20-45 years with documented height and weight from the
      day of oocyte retrieval who underwent 24-chromosome PGS between 2010 and 2013.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):  PRIMARY OUTCOMES: number and
      percentage of euploid embryos. RESULT(S): Patients were grouped by World Health
      Organization (WHO) BMI class: underweight (<18.5, n = 11), normal weight (18.5
      24.9, n = 196), overweight (25-29.9, n = 50), and obese (>=30, n = 22). Groups
      were similar by age (mean +/- standard error of the mean: 37.5 +/- 1.2 to 39.2 +/
      0.9), ovarian reserve, and IVF cycle parameters. There was no difference in the
      number or percentage of euploid embryos by BMI category (<18.5: 27.6% +/- 8.5;
      18.5-24.9: 34.5% +/- 2.2; 25-29.9: 32.1% +/- 4.3; >=30: 30.9% +/- 7.3). Age was
      inversely related to euploidy, but adjusted multivariate regression models failed
      to demonstrate a statistically significant relationship between BMI and euploidy
      in underweight (adjusted odds ratio [AOR] 0.44; 95% confidence interval [CI],
      0.09-2.10), overweight (AOR 0.90; 95% CI, 0.43-2.00), or obese (AOR 0.74; 95% CI,
      0.25-2.20) patients compared with the normal-weight reference group.
      CONCLUSION(S): No statistically significant relationship was identified between
      BMI and euploidy in an otherwise homogenous cohort of patients undergoing IVF
      with PGS, suggesting that the negative impact of overweight and obesity on IVF
      and reproductive outcomes may not be related to aneuploidy.

PMID- 25576218
TI  - Genome-wide characterization of essential, toxicity-modulating and no-phenotype
      genes in S. cerevisiae.
AB  - Based on the requirements for an organism's viability, genes can be classified
      into essential genes and non-essential genes. Non-essential genes can be further
      classified into toxicity-modulating genes and no-phenotype genes based on the
      fitness phenotype of yeast cells when the gene is deleted under DNA-damaging
      conditions. In this study, graph theoretical approaches were used to characterize
      essential, toxicity-modulating and no-phenotype genes for S. cerevisiae in the
      physical interaction (PI) network and the perturbation sensitivity (PS) network.
      We also gained previously published biological datasets to gain a more complete
      understanding of the differences and relationships between essential, toxicity
      modulating genes and no-phenotype genes. The analysis results indicate that
      toxicity-modulating genes have similar properties as essential genes, and
      toxicity-modulating genes might represent a middle ground between essential genes
      and no-phenotype genes, suggesting that cells initiate highly coordinated
      responses to damage that are similar to those needed for vital cellular
      functions. These findings may elucidate the mechanisms for understanding toxicity
      modulating processes relevant to certain diseases. 

PMID- 25576219
TI  - MicroRNA expression profiling and functional annotation analysis of their targets
      associated with the malignant transformation of oral leukoplakia.
AB  - In spite the tremendous achievements that have been acquired in the field of
      molecular biology, the underlying mechanism associated with malignant transformed
      oral leukoplakia (OLK) is still unclear and poorly understood. The aim of this
      study is to investigate the microRNA (miRNA) expression profiles in OLK and its
      aggressive transformed tissues from the white lesion of human oral mucosa. The
      original miRNA expression dataset was downloaded from Gene Expression Omnibus
      (GEO) database and differentially expressed miRNAs were identified using two
      sample t test method. Unsupervised hierarchical clustering and principal
      component analysis of these differentially expressed miRNAs indicated that 38
      miRNA candidates could significantly discriminate OLK from malignant transformed
      oral mucosa samples. Besides, potential transcription factors were predicted
      using CyTargetLinker plugin and the miRNA-mRNA regulatory network associated with
      the malignant pathogenesis was visualized in Cytoscape environment. Totally, 3
      miRNA signatures (miR-129-5p, miR-339-5p and miR-31*) were found to be hubs that
      mediated the initiation and progression of OLK from the non-malignant to the
      aggressive one via targeting various transcription factors. Functional enrichment
      analysis based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) suggested that the dysregulation of immune response was responsible for
      oral carcinogenesis. In conclusion, we constructed a miRNA-mRNA regulatory
      network associated with the malignant transformation of OLK, and screened out
      some miRNAs and transcription factors that may have prominent roles during OLK
      malignant progression. 

PMID- 25576220
TI  - MicroRNA-124 regulates glucocorticoid sensitivity by targeting phosphodiesterase
      4B in diffuse large B cell lymphoma.
AB  - Glucocorticoids (GCs) are chemotherapeutic drugs commonly used to treat
      hematological malignancies. However, a significant fraction of patients develop
      resistance to GCs during treatment. A better insight into how GC resistance
      develops is therefore needed. It was previously shown that cyclic AMP (cAMP)
      induces sensitivity to GCs by inhibiting the AKT/mTOR/MCL1 signaling, while high
      levels of phosphodiesterase 4B (PDE4B) reverse the effect of cAMP on GC responses
      in B-cell lymphoma. Here, we show that miR-124 influences GC-induced apoptosis by
      directly targeting PDE4B. Stable expression of miR-124 in diffuse large B cell
      lymphoma (DLBCL) cell lines diminished PDE4B expression. This was associated with
      increased cAMP levels, inhibition of the AKT/mTOR/MCL1 survival pathway,
      upregulation of GRalpha expression, and improved sensitivity to GCs in the
      presence of forskolin, an activator of adenylyl cyclase. Interestingly, miR-124
      did not affect GC sensitivity in the absence of forskolin, indicating that the
      effect of this miRNA is accomplished via downregulation of PDE4B expression.
      Further, restoration of PDE4B expression in miR-124 cells rescued the phenotypic
      effect of this miRNA, demonstrating the critical role of PDE4B in miR-124
      mediated regulation of the GC response. Our study supports the notion that miR
      124 could be an attractive therapeutic target for overcoming GC resistance in
      DLBCL.

PMID- 25576221
TI  - Catalase C-262T polymorphism and risk of prostate cancer: evidence from meta
      analysis.
AB  - Catalase is an important endogenous antioxidant enzyme that detoxifies hydrogen
      peroxide to oxygen and water, thus limiting the deleterious effects of reactive
      oxygen species. Several studies investigated the role of the Catalase (CAT) C
      262T gene polymorphism on the risk of prostate cancer (PCa), but get conflicting
      results. We performed a meta-analysis based on five studies, to determine whether
      Catalase C-262T polymorphism contributes to the risk of prostate cancer using
      odds ratios (OR) with 95% confidence intervals (CI). On the whole, our evidence
      indicates that CAT C-262T polymorphism significantly increases PCa risk in the
      allele comparison model (OR=1.094, 95% CI=1.015-1.178, P=0.018). In the
      stratified analysis by ethnicity, the same results are found among Caucasians
      (allele model, OR=1.090, 95% CI=1.009-1.177, P=0.028, dominant model, OR=1.108,
      95% CI=1.023-1.201, P=0.012, recessive model, OR=1.379, 95% CI=1.158-1.641,
      P=0.000, homozygous model, OR=1.429, 95% CI=1.196-1.707, P=0.000, and
      heterozygote model, OR=1.224, 95% CI=1.020-1.469, P=0.030). In conclusion, this
      meta-analysis suggests a positive correlation between Catalase C-262T
      polymorphism and the development of PCa. 

PMID- 25576222
TI  - Transcriptome analysis of distinct Lindera glauca tissues revealed the
      differences in the unigenes related to terpenoid biosynthesis.
AB  - The Lindera glauca, an economically and ecologically important tree species, has
      emerged as a novel potential plant for the intensive studies of essential oil
      owing to its characteristic aroma and medicinal property in distinct tissues.
      However, the transcriptome information and molecular research on this species is
      still unknown to date. To reveal the formation and accumulation mechanism of
      essential oil in distinct L. glauca tissues, it is crucial to analyze
      transcriptome and to identify the full repertoire of potential unigenes involved
      in terpenoid biosynthesis. In this paper, the transcriptomes of the roots,
      sarcocarps, stems, leaves and kernels of L. glauca were analyzed for the first
      time by using short-read sequencing technology (Illumina). A total of 27.2GB
      valid reads (the average length=92.7bp) was obtained from distinct L. glauca
      tissues, and then assembled de novo into 264,831 unigenes by Trinity strategy
      (mean size=560.2bp). The resulting 98,141 unigenes (38%) of all the assembled
      unigenes were annotated in multiple public databases, of which 114 potential
      unigenes were identified to be involved in the terpenoid biosynthetic
      accumulation in L. glauca. Additionally, the differential expression profiles
      revealed 675, 697, 432, 1702 and 844 high tissue-specificity expressions of
      unigenes in the roots, sarcocarps, stems, leaves and kernels of L. glauca,
      respectively. Overall, these obtained comprehensive unigene resources will
      contribute to advance the research regarding the specific plant and more
      specifically discovery of genes participating in the terpenoid pathway and its
      regulation in specific tissues of the L. glauca, but also could help the
      understanding of the differential accumulation of secondary metabolites in
      distinct plant tissues. 

PMID- 25576223
TI  - Two nearly complete mitogenomes of wheat stem borers, Cephus pygmeus (L.) and
      Cephus sareptanus Dovnar-Zapolskij (Hymenoptera: Cephidae): an unusual elongation
      of rrnS gene.
AB  - Two nearly complete mitochondrial genomes (mitogenomes) of wheat stem borers,
      Cephus pygmeus and Cephus sareptanus (Hymenoptera: Cephidae), were sequenced,
      characterised and compared with the previously known mitogenome of Cephus
      cinctus. The gene orders are mostly conserved, except for translocation of trnM
      and swapped position of trnI and trnQ. An A+T bias was found, but a deviation
      from strand asymmetry was also detected on the J strand. All protein coding genes
      (PCGs) are initiated by ATN codons, except for nad1, nad2 and atp8, and all are
      terminated with TAA, TA- or T- as a stop codon. The predicted secondary
      structures of rrnS and rrnL genes are mostly consistent with reported
      hymenopteran species. However, an unusual elongation in rrnS, not know elsewhere
      in the order, was discovered in Cephus species. Three autonomous sequences
      detected in domains I and II are mainly responsible for the length expansions.

PMID- 25576224
TI  - Identification of functional SNPs potentially served as a genetic risk factor for
      the pathogenesis of parakeratosis in the gene encoding human deoxyribonuclease I
      like 2 (DNase 1L2) implicated in terminal differentiation of keratinocytes.
AB  - In the present study, we evaluated all of the 35 non-synonymous SNPs in the gene
      encoding DNase I-like 2 (DNase 1L2), implicated in terminal differentiation of
      keratinocytes, to seek a functional SNP that would potentially affect the levels
      of in vivo DNase 1L2 activity. Based on a compiled expression analysis of the
      amino acid-substituted DNase 1L2 corresponding to each of the 35 non-synonymous
      SNPs in the gene, these 35 SNPs were grouped into 4 classes according to the
      alteration of catalytic activity caused by the corresponding amino acid
      substitution in the DNase 1L2 protein; we were able to identify 12 non-synonymous
      SNPs as functional SNPs abolishing or substantially reducing the activity. Almost
      all of the amino acid residues corresponding to the SNPs abolishing the activity
      were completely or highly conserved in not only the DNase I family, but also
      animal DNase 1L2. Each of the minor alleles of these functional SNPs producing a
      loss-of-function or low activity-harboring variant was absent in 14 different
      populations derived from 3 ethnic groups, allowing us to assume that DNASE1L2 is
      generally well conserved with regard to these non-synonymous SNPs, thereby
      avoiding any marked reduction of the enzyme activity in human populations.
      However, it seems likely that each of the minor alleles for these SNPs may serve
      as a genetic risk factor for multiple skin diseases such as psoriasis, in which
      there is an aberrant retention of nuclear chromatin in cornified keratinocytes
      through incomplete DNA degradation.

PMID- 25576225
TI  - Doubling up on the fly: NeuroMorpho.Org Meets Big Data.

PMID- 25576226
TI  - Comparison of four software packages for CT lung volumetry in healthy
      individuals.
AB  - OBJECTIVES: To compare CT lung volumetry (CTLV) measurements provided by
      different software packages, and to provide normative data for lung densitometric
      measurements in healthy individuals. METHODS: This retrospective study included
      51 chest CTs of 17 volunteers (eight men and nine women; mean age, 30 +/- 6
      years), who underwent spirometrically monitored CT at total lung capacity (TLC),
      functional residual capacity (FRC), and mean inspiratory capacity (MIC).
      Volumetric differences assessed by four commercial software packages were
      compared with analysis of variance (ANOVA) for repeated measurements and
      benchmarked against the threshold for acceptable variability between spirometric
      measurements. Mean lung density (MLD) and parenchymal heterogeneity (MLD-SD) were
      also compared with ANOVA. RESULTS: Volumetric differences ranged from 12 to 213
      ml (0.20 % to 6.45 %). Although 16/18 comparisons (among four software packages
      at TLC, MIC, and FRC) were statistically significant (P < 0.001 to P = 0.004),
      only 3/18 comparisons, one at MIC and two at FRC, exceeded the spirometry
      variability threshold. MLD and MLD-SD significantly increased with decreasing
      volumes, and were significantly larger in lower compared to upper lobes (P <
      0.001). CONCLUSIONS: Lung volumetric differences provided by different software
      packages are small. These differences should not be interpreted based on
      statistical significance alone, but together with absolute volumetric
      differences. KEY POINTS: * Volumetric differences, assessed by different CTLV
      software, are small but statistically significant. * Volumetric differences are
      smaller at TLC than at MIC and FRC. * Volumetric differences rarely exceed
      spirometric repeatability thresholds at MIC and FRC. * Differences between CTLV
      measurements should be interpreted based on comparison of absolute differences. *
      MLD increases with decreasing volumes, and is larger in lower compared to upper
      lobes.

PMID- 25576227
TI  - Acute radial nerve entrapment at the spiral groove: detection by DTI-based
      neurography.
AB  - OBJECTIVES: This study evaluated the potential of three-tesla diffusion tensor
      imaging (DTI) and tractography to detect changes of the radial (RN) and median
      (MN) nerves during transient upper arm compression by a silicon ring tourniquet.
      METHODS: Axial T2-weighted and DTI sequences (b = 700 s/mm(2), 16 gradient
      encoding directions) of 13 healthy volunteers were obtained. Fractional
      anisotropy (FA) and apparent diffusion coefficient (ADC) values of the MN and RN
      were measured at the spiral groove and further visualized in 3D by deterministic
      tractography (thresholds: FA = .15, angle change = 27 degrees ). RESULTS:
      Local/lesional RN FA values increased (p = 0.001) and ADC values decreased (p =
      0.02) during a 20-min upper arm compression, whereas no significant FA (p = 0.49)
      or ADC (p = 0.73) changes of the MN were detected. There were no T2-w nerve
      signal changes or alterations of nerve trajectories in 3D. CONCLUSIONS: Acute
      nerve compression of the RN leads to changes of its three-tesla DTI metrics.
      Peripheral nerve DTI provides non-invasive insights into the "selective"
      vulnerability of the RN at the spiral groove. KEY POINTS: * DTI-based neurography
      detects nerve changes during acute nerve compression. * Compression leads to a
      transient increase in local radial nerve FA values. * DTI provides insights into
      radial nerve vulnerability at the spiral groove.

PMID- 25576228
TI  - Chest HRCT findings in acute transformation of adult T-cell lymphoma/leukemia.
AB  - OBJECTIVES: To assess chest high-resolution computed tomography (HRCT) findings
      in patients with acute transformation of adult T cell leukaemia/lymphoma (ATLL).
      METHODS: We retrospectively identified 72 consecutive patients at our institution
      with ATLL between October 2000 and March 2014. The cases included acute type (n =
      20), lymphoma type (n = 21), smouldering type (n = 24) and chronic type (n = 7).
      Sixteen (7 men, 9 women; aged 36-85 years, mean 63.3 years) of 31 patients (24
      with smouldering and seven with chronic type; 51.6 %) developed acute
      transformation of ATLL, and had undergone chest HRCT examinations. Parenchymal
      abnormalities, enlarged lymph nodes, pericardial effusion, pleural effusion and
      skin lesions were evaluated on HRCT. RESULTS: Chest HRCT of 15 of the 16 patients
      showed abnormal findings, including ground-glass opacity (GGO) (n = 8),
      consolidation (n = 5), interlobular septal thickening (n = 5) and nodules (n =
      5). Pleural effusion was found in five patients, lymph node enlargement in 10
      patients and multiple skin thickening in two patients. CONCLUSIONS: Almost all
      patients with acute transformation of ATLL had abnormal findings on chest HRCT,
      which consisted mainly of lymph node enlargement, GGO, interlobular septal
      thickening, nodules and bilateral pleural effusions. KEY POINTS: * The
      recognition of CT findings of acute transformation is important * Almost all
      patients with acute transformation have abnormal findings on HRCT *
      Characteristic CT features are present in acute transformation of indolent ATLL.

PMID- 25576229
TI  - Iohexol versus diatrizoate for fecal/fluid tagging during CT colonography
      performed with cathartic preparation: comparison of examination quality.
AB  - OBJECTIVE: We aimed to compare iohexol vs. diatrizoate as fecal/fluid tagging
      agents for computed tomography colonography (CTC) regarding examination quality.
      METHODS: Forty prospective patients (M:F = 23:17; 63 +/- 11.6 years) received CTC
      using 50 mL (350 mgI/mL) oral iohexol for tagging. Forty other indication
      matched, age-matched, and sex-matched patients who underwent CTC using 100 mL
      diatrizoate for tagging and otherwise the same technique, were retrospectively
      identified. Two groups were compared regarding overall examination quality, per
      patient and per-segment scores of colonic bubbles (0 [no bubbles] to 5 [the
      largest amount]), and the volume, attenuation, and homogeneity (untagged,
      layered, and homogeneous) of the residual colonic fluid. RESULTS: The iohexol
      group demonstrated a greater amount of colonic bubbles than the diatrizoate
      group: mean per-patient scores +/- SD of 1.2 +/- 0.8 vs. 0.7 +/- 0.6,
      respectively (p = 0.003); and rates of segments showing >= grade 3 bubbles of
      12.9 % (85/659) vs. 1.6 % (11/695), respectively (p = 0.001). Residual colonic
      fluid amount standardized to the colonic volume did not significantly differ: 7.2
      % +/- 4.2 vs. 7.8 % +/- 3.7, respectively (p = 0.544). Tagged fluid attenuation
      was mostly comparable between groups and the fluid was homogeneously tagged in
      98.7 % (224/227) vs. 99.5 % (218/219) segments, respectively (p = 0.344). Iohexol
      caused more colonic bubbles when used during cathartic CTC. Otherwise,
      examination quality was similarly adequate with both iohexol and diatrizoate. KEY
      POINTS: * When used for tagging, iohexol caused significantly more colonic
      bubbles than diatrizoate. * The residual colonic fluid amount did not
      significantly differ between iohexol and diatrizoate. * The quality of fluid
      tagging was similarly adequate in both iohexol and diatrizoate.

PMID- 25576230
TI  - Development of an online, publicly accessible naive Bayesian decision support
      tool for mammographic mass lesions based on the American College of Radiology
      (ACR) BI-RADS lexicon.
AB  - PURPOSE: To develop and validate a decision support tool for mammographic mass
      lesions based on a standardized descriptor terminology (BI-RADS lexicon) to
      reduce variability of practice. MATERIALS AND METHODS: We used separate training
      data (1,276 lesions, 138 malignant) and validation data (1,177 lesions, 175
      malignant). We created naive Bayes (NB) classifiers from the training data with
      tenfold cross-validation. Our "inclusive model" comprised BI-RADS categories, BI
      RADS descriptors, and age as predictive variables; our "descriptor model"
      comprised BI-RADS descriptors and age. The resulting NB classifiers were applied
      to the validation data. We evaluated and compared classifier performance with ROC
      analysis. RESULTS: In the training data, the inclusive model yields an AUC of
      0.959; the descriptor model yields an AUC of 0.910 (P < 0.001). The inclusive
      model is superior to the clinical performance (BI-RADS categories alone, P <
      0.001); the descriptor model performs similarly. When applied to the validation
      data, the inclusive model yields an AUC of 0.935; the descriptor model yields an
      AUC of 0.876 (P < 0.001). Again, the inclusive model is superior to the clinical
      performance (P < 0.001); the descriptor model performs similarly. CONCLUSION: We
      consider our classifier a step towards a more uniform interpretation of
      combinations of BI-RADS descriptors. We provide our classifier at www.ebm
      radiology.com/nbmm/index.html . KEY POINTS: * We provide a decision support tool
      for mammographic masses at www.ebm-radiology.com/nbmm/index.html . * Our tool may
      reduce variability of practice in BI-RADS category assignment. * A formal
      analysis of BI-RADS descriptors may enhance radiologists' diagnostic performance.

PMID- 25576231
TI  - Measurement of oro-caecal transit time by magnetic resonance imaging.
AB  - OBJECTIVES: To assess prospectively the agreement of orocaecal transit time
      (OCTT) measurements by lactulose hydrogen breath test (LHBT) and magnetic
      resonance imaging (MRI) in healthy subjects. METHODS: Volunteers underwent
      abdominal 1.5-T MRI using axial and coronal single-shot fast-spin-echo T2
      weighted sequences, having fasted and after lactulose ingestion (10 g/125 mL).
      Imaging and H2 excretion gas-chromatography were performed concurrently every 15
      min up to 180 min. MR images were analyzed using semiautomatic segmentation to
      calculate small bowel gas volume (SBGV) and visually to detect bolus arrival in
      the caecum. Agreement between MRI- and LHBT-OCTT was assessed. RESULTS: Twenty
      eight subjects (17 men/11 women; mean age +/- standard deviation 30 +/- 8 years)
      were evaluated. Two H2 non-producers on LHBT were excluded. OCTT measured by MRI
      and LHBT was concordant in 18/26 (69 %) subjects (excellent agreement, k =
      0.924). Median SBGV was 49.0 mL (interquartile interval 44.1 - 51.6 mL). In 8/26
      (31 %) subjects, MRI showed that the lactulose bolus was in the terminal ileum
      and not the caecum when H2E increased on LHBT. Median OCTT measured by MRI was
      significantly longer than OCTT measured by LHBT [135 min (120 - 150 min) vs.
      127.5 min (105 - 150 min); p = 0.008]. Above baseline levels, correlation between
      [H2] and SBGV was significant (r = 0.964; p < 0.001). CONCLUSIONS: MRI provides
      valid measurements of OCTT and gas production in the small bowel. KEY POINTS: *
      MRI is a valid technique to measure OCTT. * Excellent agreement between MRI and
      LHBT was found. * Measuring gas production using MRI may provide evidence of
      small bowel fermentation.

PMID- 25576232
TI  - Whole-body intravoxel incoherent motion imaging.
AB  - OBJECTIVES: To investigate the technical feasibility of whole-body intravoxel
      incoherent motion (IVIM) imaging. MATERIALS AND METHODS: Whole-body MR images of
      eight healthy volunteers were acquired at 3T using a spin-echo echo-planar
      imaging sequence with eight b-values. Coronal parametrical whole-body maps of
      diffusion (D), pseudodiffusion (D*), and the perfusion fraction (Fp) were
      calculated. Image quality was rated qualitatively by two independent
      radiologists, and inter-reader reliability was tested with intra-class
      correlation coefficients (ICCs). Region of interest (ROI) analysis was performed
      in the brain, liver, kidney, and erector spinae muscle. RESULTS: Depiction of
      anatomic structures was rated as good on D maps and good to fair on D* and Fp
      maps. Exemplary mean D (10(-3) mm(2)/s), D* (10(-3) mm(2)/s) and Fp (%) values
      (+/- standard deviation) of the renal cortex were as follows: 1.7 +/- 0.2; 15.6
      +/- 6.5; 20.9 +/- 4.4. Inter-observer agreement was "substantial" to "almost
      perfect" (ICC = 0.80 - 0.92). The coefficient of variation of D* was
      significantly lower with the proposed algorithm compared to the conventional
      algorithm (p < 0.001), indicating higher stability. CONCLUSION: The proposed IVIM
      protocol allows computation of parametrical maps with good to fair image quality.
      Potential future clinical applications may include characterization of widespread
      disease such as metastatic tumours or inflammatory myopathies. KEY POINTS: * IVIM
      imaging allows estimation of tissue perfusion based on diffusion-weighted MRI. *
      In this study, a clinically suitable whole-body IVIM algorithm is presented. *
      Coronal parametrical whole-body maps showed good depiction of anatomic details. *
      Potential future applications include detection of widespread metastatic or
      inflammatory disease.

PMID- 25576233
TI  - Phosphatidylcholine contributes to in vivo (31)P MRS signal from the human liver.
AB  - OBJECTIVES: To demonstrate the overlap of the hepatic and bile phosphorus ((31)P)
      magnetic resonance (MR) spectra and provide evidence of phosphatidylcholine
      (PtdC) contribution to the in vivo hepatic (31)P MRS phosphodiester (PDE) signal,
      suggested in previous reports to be phosphoenolpyruvate (PEP). METHODS: Phantom
      measurements to assess the chemical shifts of PEP and PtdC signals were performed
      at 7 T. A retrospective analysis of hepatic 3D (31)P MR spectroscopic imaging
      (MRSI) data from 18 and five volunteers at 3 T and 7 T, respectively, was
      performed. Axial images were inspected for the presence of gallbladder, and PDE
      signals in representative spectra were quantified. RESULTS: Phantom experiments
      demonstrated the strong pH-dependence of the PEP chemical shift and proved the
      overlap of PtdC and PEP (~2 ppm relative to phosphocreatine) at hepatic pH.
      Gallbladder was covered in seven of 23 in vivo 3D-MRSI datasets. The
      PDE(gall)/gamma-ATP(liver) ratio was 4.8-fold higher (p = 0.001) in the
      gallbladder (PDE(gall)/gamma-ATP(liver) = 3.61 +/- 0.79) than in the liver
      (PDE(liver)/gamma-ATP(liver) = 0.75 +/- 0.15). In vivo 7 T (31)P MRSI allowed
      good separation of PDE components. The gallbladder is a strong source of
      contamination in adjacent (31)P MR hepatic spectra due to biliary
      phosphatidylcholine. CONCLUSIONS: In vivo (31)P MR hepatic signal at 2.06 ppm may
      represent both phosphatidylcholine and phosphoenolpyruvate, with a higher
      phosphatidylcholine contribution due to its higher concentration. KEY POINTS: *
      In vivo (31)P MRS from the gallbladder shows a dominant biliary
      phosphatidylcholine signal at 2.06 ppm. * Intrahepatic (31)P MRS signal at 2.06
      ppm may represent both intrahepatic phosphatidylcholine and phosphoenolpyruvate.
      * In vivo (31)P MRS has the potential to monitor hepatic phosphatidylcholine.

PMID- 25576234
TI  - Tetanus after envenomations caused by freshwater stingrays.
AB  - Injuries caused by freshwater stingray are common in several regions of South
      America, although they are underreported. The riverside inhabitants are the main
      victims in the Amazonian and Midwest regions of South America. The fishermen are
      injured mainly in the new focus of colonization of the rivers by freshwater
      stingrays. With the increasing population in these regions, where freshwater
      stingrays are found, there has been a significant increase in injuries within the
      general population. The highest increase occurred among tourists from other
      regions, where these animals are not known, when visiting these areas. The
      envenomations from the stingray causes prolonged and intense pain, both local and
      regionally. Generally these are associated with other local inflammatory
      manifestations, such as swelling and erythema. The injury often progresses to
      necrosis and it is considered potentially tetanogenic. A secondary infection is
      also a frequent local complication and most frequently is caused by Aeromonas
      species, usually Aeromonas hydrophila. Herein we report the first 2 cases of
      tetanus after freshwater stingray injuries: a 51-year-old men who had tetanus and
      recovered without sequel and the second a 67-year-old men who had severe tetanus
      and a deep, necrotizing soft-tissue infection with sepsis, septic shock and
      evolution to death. 

PMID- 25576235
TI  - Quantification of ricin, RCA and comparison of enzymatic activity in 18 Ricinus
      communis cultivars by isotope dilution mass spectrometry.
AB  - The seeds of the Ricinus communis (Castor bean) plant are the source of the
      economically important commodity castor oil. Castor seeds also contain the
      proteins ricin and R. communis agglutinin (RCA), two toxic lectins that are
      hazardous to human health. Radial immunodiffusion (RID) and the enzyme linked
      immunosorbent assay (ELISA) are two antibody-based methods commonly used to
      quantify ricin and RCA; however, antibodies currently used in these methods
      cannot distinguish between ricin and RCA due to the high sequence homology of the
      respective proteins. In this study, a technique combining antibody-based affinity
      capture with liquid chromatography and multiple reaction monitoring (MRM) mass
      spectrometry (MS) was used to quantify the amounts of ricin and RCA independently
      in extracts prepared from the seeds of eighteen representative cultivars of R.
      communis which were propagated under identical conditions. Additionally, liquid
      chromatography and MRM-MS was used to determine rRNA N-glycosidase activity for
      each cultivar and the overall activity in these cultivars was compared to a
      purified ricin standard. Of the cultivars studied, the average ricin content was
      9.3 mg/g seed, the average RCA content was 9.9 mg/g seed, and the enzymatic
      activity agreed with the activity of a purified ricin reference within 35%
      relative activity. 

PMID- 25576236
TI  - Identification of C-type isolectins in the venom of the scorpionfish Scorpaena
      plumieri.
AB  - Chemical analyses of the hemagglutinating fraction from Scorpaena plumieri venom
      revealed that it contains five components (Sp-CL 1-5) with similar
      chromatographic elution profiles (35-38% of acetonitrile), molecular masses
      (16,800-17,000 Da) and N-terminal sequences, suggesting that they are isoforms of
      the same protein. The amino acid sequence of Sp-CL4 was determined and shown to
      have homology with fish C-type lectins. These data demonstrate for the first time
      the presence of C-type isolectins in a scorpionfish venom. 

PMID- 25576238
TI  - In-vitro assessment of the probiotic potential of Lactobacillus plantarum KCC-24
      isolated from Italian rye-grass (Lolium multiflorum) forage.
AB  - The aim of the present study was to determine the probiotic potential of the
      lactic acid bacteria Lactobacillus plantarum KCC-24 (L. plantarum KCC-24), that
      was isolated and characterized from Italian ryegrass (Lolium multiflorum) forage.
      The following experiments were performed to assess the probiotic characteristics
      such as antifungal activity, antibiotic susceptibility, resistance to low pH,
      stimulated gastric juice and bile salts, proteolytic activity, auto-aggregation,
      cell surface hydrophobicity, and in vitro antioxidant property. The isolated L.
      plantarum KCC-24 exhibited significant antifungal activity against the various
      fungal strains of Aspergillus fumigatus (73.43%), Penicillium chrysogenum
      (59.04%), Penicillium roqueforti (56.67%), Botrytis elliptica (40.23%), Fusarium
      oxysporum (52.47%) and it was susceptible to numerous antibiotics, survived in
      low pH, was resistant to stimulated gastric juices and bile salts (0.3% w/v).
      Moreover, L. plantarum KCC-24 exhibited good proteolytic activity. In addition L.
      plantarum KCC-24 showed potent antioxidant and hydrogen peroxide resistant
      property. In conclusion, the isolated L. plantarum KCC-24 exhibited several
      characteristics to prove it's excellent as a potential probiotic candidate for
      developing quality food for ruminant animals and human.

PMID- 25576239
TI  - Nephroprotective action of renin-angiotensin-aldosterone system blockade in
      chronic kidney disease patients: the landscape after ALTITUDE and VA NEPHRON-D
      trails.
AB  - The intervention in the renin-angiotensin-aldosterone system (RAAS) is currently
      the most effective strategy that combines blood pressure lowering and
      renoprotection. Several large, randomized, controlled trials evidenced the
      renoprotective potential of the angiotensin-converting enzyme inhibitors (ACEIs)
      and angiotensin II receptor blockers (ARBs) in nephropathies of almost any
      etiology. Mineralocorticoid receptor antagonists and direct renin inhibitor,
      aliskiren, as add-on treatments to standard therapy including the optimal dose of
      ACEIs or ARBs reduce albuminuria or proteinuria and slow development of renal
      dysfunction more than placebo. No clinical evidence is available however about
      whether these strategies may influence on long-term kidney outcome. Three recent
      trials suggested that aggressive RAAS blockade, that is, combination of 2 RAAS
      blocking agents, does not decrease cardiovascular and renal morbidity and may
      carry an increased risk of serious complications. This article reviews an
      evidence-based approach on the use of RAAS-inhibiting agents in chronic kidney
      disease and considers the implementation of dual RAAS blockade with reference to
      the results of ALTITUDE and VA NEPHRON-D trails aiming to aid clinicians in their
      treatment decisions for patients with chronic kidney disease. 

PMID- 25576237
TI  - An alkaline phosphatase reporter for use in Clostridium difficile.
AB  - Clostridium difficile is an anaerobic, Gram-positive pathogen that causes severe
      gastrointestinal disease in humans and other mammals. C. difficile is notoriously
      difficult to work with and, until recently, few tools were available for genetic
      manipulation and molecular analyses. Despite the recent advances in the field,
      there is no simple or cost-effective technique for measuring gene transcription
      in C. difficile other than direct transcriptional analyses (e.g., quantitative
      real-time PCR and RNA-seq), which are time-consuming, expensive and difficult to
      scale-up. We describe the development of an in vivo reporter assay that can
      provide qualitative and quantitative measurements of C. difficile gene
      expression. Using the Enterococcus faecalis alkaline phosphatase gene, phoZ, we
      measured expression of C. difficile genes using a colorimetric alkaline
      phosphatase assay. We show that inducible alkaline phosphatase activity
      correlates directly with native gene expression. The ability to analyze gene
      expression using a standard reporter is an important and critically needed tool
      to study gene regulation and design genetic screens for C. difficile and other
      anaerobic clostridia.

PMID- 25576240
TI  - Endothelial progenitor cells and asymmetric dimethylarginine after renal
      transplantation.
AB  - Levels of the endogenous nitric oxide synthase inhibitor asymmetrical
      dimethylarginine (ADMA) are elevated and endothelial progenitor cells (EPCs)
      decreased in patients undergoing renal transplantation (Tx) and may contribute to
      cardiovascular complications. In this study, we tested the hypothesis that
      elevated ADMA and decreased EPC can be positively influenced with regular
      physical exercise early after Tx. Blood samples for analysis of ADMA and EPC were
      obtained from randomly selected 64 patients after Tx who agreed to participate in
      a supervised aerobic exercise program for 6 months (group I). Samples were
      collected before the training began, 1 month after surgery (with stabilized renal
      function), and at 6 months after initiation. Sixty-two age, sex, human leukocyte
      antigens (HLA) typing, duration of previous dialysis, history of cardiovascular
      disease, and immunosupression regimen-matched transplant patients who did not
      exercise regularly were examined as controls (group II). There were no
      differences in ADMA levels and EPC count between both groups before the training
      program began. After 6 months of exercise, ADMA concentration in the group I
      decreased (3.50 +/- 0.45 vs. 2.11 +/- 0.35 MUmol/L; P < .01) and was also lower
      comparing with group II (2.11 +/- 0.23 vs. 3.25 +/- 0.35 MUmol/L; P < .01). In
      the same period, EPC cells increased from 2.085 +/- 650 cells/mL versus 3.991 +/-
      560 cells/mL, P < .01 in group I; but in group II, changes were nonsignificant (P
      = .11). Blood lipids, HbA1c, insulin, and systolic blood pressure were also
      affected by the training program. Elevated ADMA level and decreased EPC count
      were significantly influenced by early regular exercise in patients after Tx.

PMID- 25576241
TI  - Exome sequencing reveals three novel candidate predisposition genes for diffuse
      gastric cancer.
AB  - Gastric cancer is the fourth most common cancer worldwide and the second leading
      cause of cancer mortality. Three hereditary gastric cancer syndromes have been
      described; hereditary diffuse gastric cancer (HDGC), familial intestinal gastric
      cancer (FIGC) and gastric adenocarcinoma and proximal polyposis of the stomach
      (GAPPS). Thirty per cent of HDGC families have heterozygous germline mutations in
      CDH1, which encodes E-cadherin. A germline truncating mutation in the gene
      encoding alpha-E-catenin (CTNNA1) was also recently discovered in a family with
      HDGC, but no other genes specifically predisposing to gastric cancer have been
      identified, leaving the majority of cases showing familial aggregation without a
      known genetic cause. The aim of this study was to find the putative gastric
      cancer predisposing gene defect in a family with HDGC that had previously been
      tested negative for mutations in CDH1. In this family, there were six cases of
      diffuse gastric cancer in two generations. Exome sequencing was applied to two
      affected family members. The shared variants which were predicted deleterious in
      silico and could not be found in databases or in a control set of over 4,000
      individuals were Sanger sequenced in a third family member. Three candidate
      variants were identified: p.Glu1313Lys in Insulin receptor (INSR), p.Arg81Pro in
      F-box protein 24 (FBXO24) and p.Pro1146Leu in DOT1-like histone H3K79
      methyltransferase (DOT1L). These variants and adjacent regions were screened for
      in an additional 26 gastric cancer patients with a confirmed (n = 13) or
      suspected (n = 13) family history of disease, but no other non-synonymous
      mutations were identified. This study identifies INSR, FBXO24 and DOT1L as new
      candidate diffuse gastric cancer susceptibility genes, which should be validated
      in other populations. Of these genes, INSR is of special interest as insulin
      signaling was recently shown to affect tumor cell invasion capability by
      modulating E-cadherin glycosylation.

PMID- 25576242
TI  - Thyroid autoimmunity as a window to autoimmunity: An explanation for sex
      differences in the prevalence of thyroid autoimmunity.
AB  - Autoimmune thyroid diseases (AITDs), predominately Graves' disease and
      Hashimoto's thyroiditis, comprise the most common autoimmune diseases in humans.
      Both have the production of anti-thyroid antibody as an important aspect and both
      are much more prevalent in females, being at least 10 times more common than in
      males. Using these two clues, a hypothesis for the initiation of thyroid
      autoimmunity is proposed that helps to make the case that the thyroid is one of
      the most sensitive sites for autoimmunity and helps account for the prevalence
      and the observed sex differences in AITDs and associated diseases, such as type 1
      diabetes and Latent Autoimmune Diabetes in Adults (LADA). The primary mechanisms
      proposed involve the underlying state of inflammation as a result of the
      adipokines, especially leptin, TNF-alpha, and IL-6, and the receptors able to
      recognize pathogen-associated molecular patterns (PAMP's) and damage-associated
      molecular patterns (DAMP's) through Toll-like receptors (TLR) and others
      receptors present on thyrocytes. The adipokines are produced by adipose tissue,
      but have hormone-like and immune modulating properties. As the levels of leptin
      are significantly higher in females, an explanation for the sex difference in
      thyroid autoimmunity emerges. The ability of the thyrocytes to participate in
      innate immunity through the TLR provides an adjuvant-like signal and allows for
      the action of other agents, such as environmental factors, viruses, bacteria, and
      even stress to provide the initiation step to break tolerance to thyroid self
      antigens. Seeing the thyroid as one of the most sensitive sites for autoimmunity,
      means that for many autoimmune disorders, if autoimmunity is present, it is
      likely to also be present in the thyroid - and that that condition in the thyroid
      was probably earlier. The evidence is seen in multiple autoimmune syndrome. 

PMID- 25576243
TI  - Persistence and breakdown of strand symmetry in the human genome.
AB  - Afreixo, V., Bastos, C.A.C., Garcia, S.P., Rodrigues, J.M.O.S., Pinho, A.J.,
      Ferreira, P.J.S.G., 2013. The breakdown of the word symmetry in the human genome.
      J. Theor. Biol. 335, 153-159 analyzed the word symmetry (strand symmetry or the
      second parity rule) in the human genome. They concluded that strand symmetry
      holds for oligonucleotides up to 6 nt and is no longer statistically significant
      for oligonucleotides of higher orders. However, although they provided some new
      results for the issue, their interpretation would not be fully justified. Also,
      their conclusion needs to be further evaluated. Further analysis of their
      results, especially those of equivalence tests and word symmetry distance, shows
      that strand symmetry would persist for higher-order oligonucleotides up to 9 nt
      in the human genome, at least for its overall frequency framework
      (oligonucleotide frequency pattern). 

PMID- 25576244
TI  - Decreased levels of serum omentin-1 in patients with inflammatory bowel disease.
AB  - BACKGROUND: Inflammation is involved in the mechanism of inflammatory bowel
      disease (IBD). Omentin, a newly discovered adipokine, is thought to play an anti
      inflammatory role. This study aimed to determine whether serum levels of omentin
      1 are associated with the presence and disease activity of IBD. MATERIAL/METHODS:
      This study consisted of 192 patients with IBD: 100 with Crohn's disease [CD], 92
      with ulcerative colitis [UC], and 104 healthy subjects. Serum levels of omentin-1
      were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum
      omentin-1 levels were significantly decreased in CD and UC patients compared with
      healthy controls. Multivariable logistic regression analysis revealed that serum
      omentin-1 levels were inversely associated with the presence of CD and UC. Active
      CD and UC patients both had significantly decreased levels of serum omentin-1
      compared with inactive CD and UC patients. In both CD and UC patients, serum
      omentin-1 levels were significantly associated with decreased levels of body mass
      index (BMI) and C-reactive protein (CRP). CONCLUSIONS: Decreased serum omentin-1
      levels could be considered as an independent predicting marker of the presence
      and disease activity of IBD.

PMID- 25576245
TI  - Evaluation of Spray BIO-Max DIM-P in Dogs for Oral Bioavailability and in Nu/nu
      Mice Bearing Orthotopic/Metastatic Lung Tumor Models for Anticancer Activity.
AB  - PURPOSE: In an effort to prepare an oral dosage form for poorly bioavailable anti
      cancer agents, we have incorporated spray drying using a customized spray gun
      generating enteric coated Self-emulsifying drug delivery systems. The objective
      of this study was to design and evaluate pharmacokinetics and pharmacodynamic
      characteristics of Spray BIO-Max DIM-P (SB DIM-P). METHODS: SB DIM-P was prepared
      and optimized based on physico-chemical characteristics using design of
      experiment (DOE-Vr 8.0) software. Pharmacokinetic parameters in dogs and rats
      were evaluated and analyzed using Winonlin. Anti-tumor activity was carried out
      in orthotopic and metastatic lung tumor models using size M capsules in mice.
      RESULTS: Based on the optimization using DOE analysis of SB DIM-P
      characteristics, formulations were selected for further investigation.
      Pharmacokinetic studies showed a 30% increase in oral bioavailability in rats and
      ~2.9 times more bioavailability of SB DIM-P compare to solution in dogs. SB DIM-P
      showed ~20-25% more tumor volume/weight reduction in H1650 metastatic tumor model
      and ~25-30% tumor volume/weight reduction in A549 orthotopic tumor model compared
      to DIM-P solution. CONCLUSIONS: Our studies demonstrate the potential application
      of spray dried enteric coated self-emulsifying delivery system (SB DIM-P) to
      enhances oral absorption and efficacy of DIM-P in lung tumor models.

PMID- 25576246
TI  - NMR spectroscopic and quantum mechanical analyses of enhanced solubilization of
      hesperidin by theasinensin a.
AB  - PURPOSE: The use of hesperidin in the pharmaceutical field is limited by its
      aqueous insolubility. The effects of natural compounds in tea on the solubility
      of hesperidin were evaluated and the underlying mechanism was investigated by
      nuclear-magnetic resonance (NMR) and quantum mechanical calculations. METHODS:
      The solubility of hesperidin was measured by liquid chromatography time-of-flight
      mass spectrometry; the structure of the hesperidin/theasinensin A complex was
      characterized by (1)H-NMR, diffusion-ordered NMR spectroscopy, and rotating frame
      NOE spectroscopy, as well as theoretically by quantum mechanical calculations.
      RESULTS: Among the natural compounds in tea, theasinensin A was the most
      effective in improving hesperidin solubility. The complexation of hesperidin with
      theasinensin A led to changes in the chemical shift of protons in hesperidin
      (Deltadelta: 0.01-0.27 ppm) and diffusion coefficient (DeltaD: 0.66-1.32 * 10(
      10) m(2)/s) of hesperidin. ROE correlation signals between hesperidin and
      theasinensin A and quantum mechanical calculations revealed that two hesperidin
      molecules formed a stable complex with theasinensin A (2:1 complex) with a DeltaG
      energy of -23.5 kJ/mol. CONCLUSIONS: This is the first study that provides
      insight into the enhanced solubility of hesperidin through interactions with
      theasinensin A via a 2:1 complex formation between hesperidin and theasinensin A.

PMID- 25576247
TI  - Lessons from conducting trans-national Internet-mediated participatory research
      with hidden populations of cannabis cultivators.
AB  - BACKGROUND: Internet-mediated research methods are increasingly used to access
      hidden populations. The International Cannabis Cultivation Questionnaire (ICCQ)
      is an online survey designed to facilitate international comparisons into the
      relatively under-researched but increasingly significant phenomenon of domestic
      cannabis cultivation. The Global Cannabis Cultivation Research Consortium has
      used the ICCQ to survey over 6000 cannabis cultivators across 11 countries. In
      this paper, we describe and reflect upon our methodological approach, focusing on
      the digital and traditional recruitment methods used to access this hidden
      population and the challenges of working across multiple countries, cultures and
      languages. METHODS: Descriptive statistics showing eligibility and completion
      rates and recruitment source by country of residence. RESULTS: Over three
      quarters of eligible respondents who were presented with the survey were included
      in the final sample of n=6528. English-speaking countries expended more effort to
      recruit participants than non-English-speaking countries. The most effective
      recruitment modes were cannabis websites/groups (33%), Facebook (14%) and news
      articles (11%). While respondents recruited through news articles were older,
      growing practice variables were strikingly similar between these main recruitment
      modes. CONCLUSION: Through this process, we learnt that there are trade-offs
      between hosting multiple surveys in each country vs. using one integrated
      database. We also found that although perceived anonymity is routinely assumed to
      be a benefit of using digital research methodologies, there are significant
      limits to research participant anonymity in the current era of mass digital
      surveillance, especially when the target group is particularly concerned about
      evading law enforcement. Finally, we list a number of specific recommendations
      for future researchers utilising Internet-mediated approaches to researching
      hidden populations.

PMID- 25576249
TI  - Erratum to: Reverse shoulder arthroplasty in acute fractures provides better
      results than in revision procedures for fracture sequelae.

PMID- 25576248
TI  - Timing of surgical decompression for traumatic cervical spinal cord injury.
AB  - PURPOSE: Although there have been numerous studies aimed at determining the
      effects and safety of early vs. late surgical decompression for traumatic
      cervical spinal cord injury, controversies still exist regarding the optimal
      timing of surgery for this serious spinal trauma. This study was conducted to
      evaluate the effectiveness and safety of early vs. late surgical decompression
      for lower cervical spine trauma associated with spinal cord injury. METHODS: A
      retrospective review of was performed on consecutive patients who underwent
      surgical decompression for lower cervical (C3-C7) spine trauma associated with
      spinal cord injury at six institutions across China from January 2007 to January
      2012. These patients were analysed according to the timing of surgical
      intervention. The early group comprised patients who underwent surgery within the
      first 72 hours after being injured, whilst the late group comprised patients who
      underwent surgery after the first 72 hours. For analysis of neurologic
      improvement, patients who had completed a follow-up of at least six months were
      assessed. Other outcomes analysed were hospitalisation periods, complications and
      mortality. RESULTS: A total of 595 patients were identified (456 men and 139
      women at an average age of 41.4 years), with 212 in the early group and 383 in
      the late group. Patients in both groups had made a significant neurologic
      improvement in the final follow-up, but no statistically significant difference
      was noted between groups. Patients in the early group had a significantly shorter
      hospital stay (15.4 vs. 18.3 days, p <0.001) but realised no benefits in terms of
      intensive care unit length of stay and ventilator days. No significant
      differences were identified between groups with regards complications (pneumonia,
      pulmonary embolism, wound infection, sepsis and urinary tract infection).
      Compared with the late group, the early group had a significantly higher
      incidence of postoperative neurological deterioration (6.6 vs. 0.7 %, p <0.001)
      and mortality (7.1 vs. 2.1 %, p = 0.003). CONCLUSION: The timing of surgery for
      patients sustaining traumatic lower cervical spine injury with neurological
      involvement did not affect neurological recovery. Early surgical intervention was
      associated with a higher incidence of mortality and neurological deterioration
      compared with late surgical intervention, indicating that surgery after the first
      72 hours might be relatively safe.

PMID- 25576251
TI  - Identification of microRNAs differentially expressed involved in male flower
      development.
AB  - Hickory (Carya cathayensis Sarg.) is one of the most economically important woody
      trees in eastern China, but its long flowering phase delays yield. Our
      understanding of the regulatory roles of microRNAs (miRNAs) in male flower
      development in hickory remains poor. Using high-throughput sequencing technology,
      we have pyrosequenced two small RNA libraries from two male flower
      differentiation stages in hickory. Analysis of the sequencing data identified 114
      conserved miRNAs that belonged to 23 miRNA families, five novel miRNAs including
      their corresponding miRNA*s, and 22 plausible miRNA candidates. Differential
      expression analysis revealed 12 miRNA sequences that were upregulated in the
      later (reproductive) stage of male flower development. Quantitative real-time PCR
      showed similar expression trends as that of the deep sequencing. Novel miRNAs and
      plausible miRNA candidates were predicted using bioinformatic analysis methods.
      The miRNAs newly identified in this study have increased the number of known
      miRNAs in hickory, and the identification of differentially expressed miRNAs will
      provide new avenues for studies into miRNAs involved in the process of male
      flower development in hickory and other related trees. 

PMID- 25576252
TI  - [Aspirin and venous thromboses].
AB  - BACKGROUND: The pharmacological prevention of venous thromboembolism (VTE) has so
      far been carried out mainly with classic (low-molecular-weight heparins,
      coumarins) or new direct oral anticoagulants (DOACs). The role of antiplatelet
      treatment with aspirin is controversial. New data, however, suggest a paradigm
      shift with the reassessment of aspirin as part of a multimodal antithrombotic
      approach. OBJECTIVE: The article provides an up-to-date overview of the role of
      antiplatelet treatment with aspirin in the primary and secondary prevention of
      VTE. CURRENT DATA AND RESULTS: Primary prevention of surgery-related VTE with
      anticoagulants is effective but apparently not superior to a multimodal approach
      with aspirin, pneumatic compression, and early mobilization. Against this
      background, aspirin is now also included in the VTE prevention guidelines in the
      US (ACCP, AAOS) but not in the UK (NICE) and Germany (AMWF). A final evaluation
      of aspirin as compared to classic anticoagulants and DOACs in primary prophylaxis
      requires further randomized controlled, prospective trials. These should also
      consider the iatrogenic risk of bleeding as well as possible postoperative
      complications, such as retarded wound healing that might require prolonged
      hospitalization. After ending guideline-conforming anticoagulant treatment in
      patients with idiopathic VTE, administration of aspirin reduces the risk of
      recurrent VTE by about 40% without increasing the risk of severe bleeding
      (standardized INSPIRE evaluation of ASPIRE and WARFASA data). These data add to
      the current use of aspirin in the prevention of arterial thrombosis the new
      option of preventing spontaneous VTE. CONCLUSION: On the basis of new data from
      recent studies, an indication can be made for the use of aspirin, combined with
      other preventive measures, in the prevention of primary and secondary venous
      thromboses.

PMID- 25576254
TI  - Presarcopenia and sarcopenia in hip-fracture women: prevalence and association
      with ability to function in activities of daily living.
AB  - BACKGROUND AND AIMS: Sarcopenia staging systems have been proposed, but little is
      known on their application in hip-fracture patients. Our aim was to assess the
      prevalence of presarcopenia and sarcopenia and their association with ability to
      function in activities of daily living in hip-fracture women. METHODS: We
      investigated white women (N = 138 of 149) who were consecutively admitted to a
      rehabilitation hospital because of their first hip fracture. In each woman, we
      measured appendicular lean mass (aLM) by dual-energy X-ray absorptiometry, at a
      median of 18 days after hip fracture occurrence. On the same day, we assessed
      grip strength with a handheld dynamometer. Functional autonomy was assessed by
      the Barthel Index. We used the European Working Group on Sarcopenia in Older
      People (EWGSOP) definition to calculate the prevalence of presarcopenia and
      sarcopenia, taking into account both aLM/height(2) and handgrip strength. Gait
      speed was not considered, because of the recent hip fracture. RESULTS: Twenty
      three (17 %) of the 138 women fulfilled the diagnostic criteria for presarcopenia
      whereas 80 (58 %) were sarcopenic. The women with presarcopenia were younger,
      healthier and with higher Barthel Index scores (median 65 vs. 55; interquartile
      range 60-75 and 50-60, respectively; p < 0.001) than those with sarcopenia.
      Significant differences in Barthel Index scores at the time of assessment (but
      not at the end of the rehabilitation course) persisted after multiple adjustments
      (p < 0.001). CONCLUSIONS: The prevalence of presarcopenia and sarcopenia was high
      in hip-fracture women. Presarcopenic women had higher ability to function in
      activities of daily living than sarcopenic women.

PMID- 25576253
TI  - Repeated application of 4-aminopyridine provoke an increase in entorhinal cortex
      excitability and rearrange AMPA and kainate receptors.
AB  - Entorhinal cortex is a highly epilepsy-prone brain region. Effects of repetitive
      seizures on ionotropic glutamate receptors (iGluRs) were investigated in rat
      entorhinal cortex slices. Seizures were induced by daily administration of 4
      aminopyridine (4-AP). Electrophysiological, pharmacological and histological
      investigations were carried out to determine changes in synaptic efficacy and in
      sensitivity of iGluRs due to recurring seizures. Repeated 4-AP-induced seizures
      increased the amplitude of evoked synaptic field responses in rat entorhinal
      cortical slices. While vulnerability to inhibition of AMPA receptors by the
      specific antagonist GYKI 52466 was slightly reduced, responsiveness to NMDA
      receptor antagonist APV remained unaffected. Testing of bivalent cation
      permeability of iGluRs revealed reduced Ca(2+)-influx through non-NMDA receptors.
      According to the semi-quantitative histoblot analysis GluA1-4, GluA1, GluA2,
      GluK5, GluN1 and GluN2A subunit protein expression differently altered. While
      there was a marked decrease in the level of GluA1-4, GluA2 and GluK5 receptor
      subunits, GluA1 and GluN2A protein levels moderately increased. The results
      indicate that brief convulsions, repeated daily for 10 days can increase overall
      entorhinal cortex excitability despite a reduction in AMPA/kainate receptor
      activity, probably through the alteration of local network susceptibility.

PMID- 25576255
TI  - Simultaneous bilateral femoral neck fracture and end-stage renal disease in a 76
      year-old woman: a case report.
AB  - Hip fracture is a common occurrence in the elderly. Due to the growing demand for
      the specific care of these patients, we established the Orthogeriatric Unit (OGU)
      at San Gerardo University Hospital (Italy) in 2007. However, simultaneous
      bilateral femoral neck fractures among the geriatric population (those aged >=65
      years) are rarely reported in the literature. Reporting the rare case of a frail
      76-year-old woman admitted with bilateral hip fracture and end-stage renal
      disease, we explain the important role played by the OGU and its flexible
      multidisciplinary approach for providing comprehensive care to patients with
      multimorbidity and clinical complexity. The team of geriatricians, orthopedic
      surgeons, anesthesiologists, and, in this case, a nephrologist, helped in the
      careful planning and timing of the single-step surgical repair, decided the
      appropriate type of anesthesia, and optimized outcomes. After a prompt evaluation
      of the patient, the OGU approach can achieve clinical stabilization prior to
      intervention. Along with a strict follow-up in the postoperative phase, this
      could result in a significant reduction of complications and mortality rates and
      an early start to a tailored rehabilitation process. We strongly suggest
      employing facilities with multidisciplinary teams for cases involving complex
      patients at short-term high risk for poor clinical outcomes. Indeed, the usual
      single-specialist model of care is gradually being abandoned worldwide. 

PMID- 25576256
TI  - Mucus permeating carriers: formulation and characterization of highly densely
      charged nanoparticles.
AB  - The GI mucus layer represents a significant block to drug carriers absorption.
      Taking an example from nature, virus-mimicking nanoparticles (NPs) with highly
      densely charged surface were designed with the aim to improve their mucus
      permeation ability. NPs were formulated by combining chitosan with chondroitin
      sulfate and were characterized by particle size, zeta-potential and
      hydrophobicity. The interaction occurring between NPs and diluted porcine
      intestinal mucus was investigated by a new method. Furthermore, the rotating tube
      technique was exploited to evaluate the NPs permeation ability in fresh undiluted
      porcine intestinal mucus. NPs (400-500 nm) presenting a slightly positive (4.02
      mV) and slightly negative (-3.55 mV) zeta-potential resulted to be hydrophobic
      and hydrophilic, respectively. On the one hand the hydrophobic NPs undergo
      physico-chemical changes when incubated with mucus, namely the size increased and
      the zeta-potential decreased. On the other hand, the hydrophilic NPs did not
      significantly change size and net charge during incubation with mucus. Both types
      of NPs showed a 3-fold higher diffusion ability compared to the reference 50/50
      DL-lactide/glycolide copolymer NPs (136 nm, -23 mV, hydrophilic). Based on these
      results, this work gives valuable information for the further design of mucus
      penetrating NPs.

PMID- 25576257
TI  - Exploratory study on association of single-nucleotide polymorphisms with
      hydromorphone analgesia in ED.
AB  - OBJECTIVES: The objective of this study is to provide information on distribution
      of important single-nucleotide polymorphisms (SNPs) and evaluate their
      associations with clinical response to intravenous hydromorphone in emergency
      department. METHODS: A prospective exploratory study was performed. A convenience
      sample of adult emergency department patients with acute pain deemed to require
      intravenous opioids received 1 mg of intravenous hydromorphone. Primary outcome
      was pain score (numeric rating scale, NRS) reduction between baseline and 30
      minutes after medication administration. Secondary outcomes were pain relief,
      patient satisfaction with analgesia, desire for more analgesics, and side effects
      (nausea, vomiting, and pruritis). Single-nucleotide polymorphisms in OPRM1 gene
      (opioid receptor, A118G), ABCB1 gene (opioid transporter, C3435T), COMT gene
      (pain sensitivity, G1947A), and UGT2B7 gene (opioid metabolism, -G840A) were
      tested. We used Kruskal-Wallis test to compare the primary outcome and chi(2)
      test (or Fisher test) to compare the secondary outcomes among patients carrying
      different SNPs. RESULTS: One thousand four hundred thirty-eight patients were
      screened, and 163 patients were enrolled in the study. The mean age was 39 years.
      Sixty-three percent were female, 58% were Hispanic, and 67% had pain located in
      abdomen. The median pain NRS reduction at 30 minutes was 5 (interquartile range,
      3-8). There was no difference in pain NRS reduction among patients carrying
      different SNPs. Secondary outcome analysis revealed statistically significant
      associations between patient satisfaction with treatment and OPRM1 and between
      nausea and UGT2B7. CONCLUSIONS: This exploratory study did not show a significant
      difference in pain NRS reduction among patients carrying different SNPs. Patient
      satisfaction with analgesia and nausea were statistically significantly
      associated with OPRM1 and UGT2B7, respectively.

PMID- 25576258
TI  - Transient ischemic attack related to sweetened beverage consumption.

PMID- 25576259
TI  - [Combined treatment of sildenafil and inhaled iloprost in pediatric patients with
      severe pulmonary arterial hypertension].

PMID- 25576260
TI  - [Persistent fifth aortic arch with patent ductus arteriosus].
AB  - Persistent fifth aortic arch is a rare congenital vascular anomaly, with no
      clinical impact, so diagnosis is usually an incidental finding occasionally
      associated with other congenital heart defects. We report a case of persistent
      fifth aortic arch associated with patent ductus arteriosus.

PMID- 25576261
TI  - On the nature of the electromyographic signals recorded during vibration
      exercise.
AB  - PURPOSE: Surface electromyography (EMG) has been widely used to measure
      neuromuscular activity during vibration exercise (VE) to investigate the
      underlying mechanisms elicited by VE. However, the EMG spectrum recorded during
      VE shows sharp peaks at the vibration frequency whose interpretation remains
      controversial. Some authors considered those peaks as a result of motion
      artifacts, while others interpreted them as due to vibration-induced
      neuromuscular activity. The aim of the present study is to clarify the nature of
      those sharp peaks observed during VE. METHODS: Three independent EMG measurements
      were performed during VE: in vitro (IVT), in vivo at rest ([Formula: see text]),
      and in vivo during voluntary contraction ([Formula: see text]). The amplitudes of
      the EMG vibration frequency components ([Formula: see text]) were extracted for
      all measurements. The conduction velocity (CV) of the vibration frequency
      components and the full EMG spectrum were also estimated during voluntary
      contraction. RESULTS: Our spectrum analysis revealed small [Formula: see text]
      for IVT and [Formula: see text], accounting for only 3.3 and 7.6 % of that
      obtained from [Formula: see text]. Moreover, the CV estimation indicated the EMG
      vibration components to propagate along the muscle fiber with CV [Formula: see
      text] 6.5 m/s, comparable to the CV estimated using the full EMG spectrum (5.7
      m/s). CONCLUSION: We may therefore conclude that the sharp spectral peaks
      observed during VE are mainly due to vibration-induced muscle activity rather
      than motion artifacts.

PMID- 25576262
TI  - Non-invasive estimation of hydration status changes through tear fluid osmolarity
      during exercise and post-exercise rehydration.
AB  - PURPOSE: To determine if tear fluid osmolarity (Tosm) can track changes in
      hydration status during exercise and post-exercise rehydration. METHODS: Nineteen
      male athletes (18-37 years, 74.6 +/- 7.9 kg) completed two randomized,
      counterbalanced trials; cycling (~95 min) with water intake to replace fluid
      losses or water restriction to progressively dehydrate to 3 % body mass loss
      (BML). After exercise, subjects drank water to maintain body mass (water intake
      trials) or progressively rehydrate to pre-exercise body mass (water restriction
      trials) over a 90-min recovery period. Plasma osmolality (Posm) and Tosm
      measurements (mean of right and left eyes) were taken pre-exercise, during rest
      periods between exercise bouts corresponding to 1, 2, and 3 % BML, and
      rehydration at 2, 1, and 0 % BML. RESULTS: During exercise mean (+/- SD) Tosm was
      significantly higher in water restriction vs. water intake trials at 1 % BML (299
      +/- 9 vs. 293 +/- 9 mmol/L), 2 % BML (301 +/- 9 vs. 294 +/- 9 mmol/L), and 3 %
      BML (302 +/- 9 vs. 292 +/- 8 mmol/L). Mean Tosm progressively decreased during
      post-exercise rehydration and was not different between trials at 1 % BML (291 +/
      8 vs. 290 +/- 7 mmol/L) and 0 % BML (288 +/- 7 vs. 289 +/- 8 mmol/L). Mean Tosm
      tracked changes in hydration status similar to that of mean Posm; however, the
      individual responses in Tosm to water restriction and water intake was
      considerably more variable than that of Posm. CONCLUSION: Tosm is a valid
      indicator of changes in hydration status when looking at the group mean; however,
      large differences among subjects in the Tosm response to hydration changes limit
      its validity for individual recommendations.

PMID- 25576264
TI  - Animals and memory.

PMID- 25576263
TI  - Acute effect of static exercise on the cardiovascular system: assessment by
      cardiovascular magnetic resonance.
AB  - PURPOSE: The acute effect of static exercise on the global dynamics of the
      cardiovascular system is poorly understood. The use of cardiovascular magnetic
      resonance (CMR) may be useful for evaluating this effect. METHODS: A total of 12
      healthy individuals underwent CMR imaging at rest and while performing a maximal
      sustained static exercise (weight elevation with both legs). We analyzed the
      effects on left and right ventricular function, ascending aorta dynamics, and
      venous capacitance using standard cine and phase-contrast sequences. RESULTS: We
      observed excellent reproducibility in the measurements of the images obtained at
      rest as well as during static exercise. During exercise, we observed reduced left
      (-35 +/- 8 %, p < 0.001) and right (-44 +/- 9 %, p < 0.001) ventricle end
      diastolic volumes, reduced left (-35 +/- 16 %, p < 0.001) and right (-43 +/- 8 %,
      p < 0.001) ventricle end-systolic volumes (both with a significantly greater
      reduction in the right ventricle), a reduced superior vena cava cross-sectional
      area (-20 +/- 17 %, p = 0.003), and increased left ventricle wall thickness. We
      estimated that there was an increase in left ventricle contractility. There were
      no significant changes in the left and right ventricular ejection fractions.
      During exercise, we noted a tendency toward decreased aortic distensibility and a
      reduction of ascending aorta systolic expansion. CONCLUSIONS: In healthy
      individuals, an acute maximal static exercise produced a reduction in the left
      ventricle, right ventricle, and superior vena cava volumes as well as signs of
      increased aortic stiffness without increasing left ventricular systolic wall
      stress. CMR is feasible and useful in evaluating the hemodynamic effects of
      static exercise.

PMID- 25576265
TI  - Veterinary homeopathy: meta-analysis of randomised placebo-controlled trials.
AB  - BACKGROUND: Meta-analysis of randomised controlled trials (RCTs) of veterinary
      homeopathy has not previously been undertaken. For all medical conditions and
      species collectively, we tested the hypothesis that the outcome of homeopathic
      intervention (treatment and/or prophylaxis, individualised and/or non
      individualised) is distinguishable from corresponding intervention using
      placebos. METHODS: All facets of the review, including literature search
      strategy, study eligibility, data extraction and assessment of risk of bias, were
      described in an earlier paper. A trial was judged to comprise reliable evidence
      if its risk of bias was low or was unclear in specific domains of assessment.
      Effect size was reported as odds ratio (OR). A trial was judged free of vested
      interest if it was not funded by a homeopathic pharmacy. Meta-analysis was
      conducted using the random-effects model, with hypothesis-driven sensitivity
      analysis based on risk of bias. RESULTS: Nine of 15 trials with extractable data
      displayed high risk of bias; low or unclear risk of bias was attributed to each
      of the remaining six trials, only two of which comprised reliable evidence
      without overt vested interest. For all N = 15 trials, pooled OR = 1.69 [95%
      confidence interval (CI), 1.12 to 2.56]; P = 0.01. For the N = 2 trials with
      suitably reliable evidence, pooled OR = 2.62 [95% CI, 1.13 to 6.05]; P = 0.02).
      CONCLUSIONS: Meta-analysis provides some very limited evidence that clinical
      intervention in animals using homeopathic medicines is distinguishable from
      corresponding intervention using placebos. The low number and quality of the
      trials hinders a more decisive conclusion.

PMID- 25576266
TI  - Effect of a homeopathic complex on reproductive performance in a commercial pig
      farm.
AB  - BACKGROUND AND AIM: Alternative therapies based on homeopathy can be effective in
      improving reproductive performance in intensive pig breeding. In this study, the
      effect of a homeopathic complex on reproductive performance of sows under
      intensive farming has been investigated. MATERIAL AND METHODS: Over period of
      three years, 186 sows were recruited from a farm where a large proportion of
      animals were suffering from prolonged weaning-to-oestrus intervals (WEI) and
      weaning-to-service intervals (WSI). Sows were allocated to two groups; once per
      month, one group was given a homeopathic complex (Borax 10 mK plus Lycopodium 10
      mK), while the other group was given a hydro-alcoholic solution (placebo). The
      follow-up period started one week before the expected date of oestrus, continued
      for two pregnancies and ended after the weaning of the second farrowing. To
      evaluate reproductive performance, during the follow-up we collected data on
      quantitative parameters such as the average number of stillbirths, newborns, and
      repeat services per farrowing. Time-related data such as WEI, WSI, length of the
      two pregnancies and weaning periods were also collected to measure the length of
      the follow-up of each sow. Differences in quantitative parameters between the two
      groups were evaluated using parametric and non-parametric statistics. Time
      related data were used to plot Kaplan-Meier curves and in Cox regression models
      to evaluate whether treated sows had a higher probability of experiencing a
      shorter follow-up in comparison to untreated sows. RESULTS: We did not found
      significant differences in the number of newborns, while the number of
      stillbirths was higher in the treatment group, even if the difference was
      slightly significant (p-value = 0.03). The number of repeat services was lower in
      the treatment group, and this difference was highly significant (p-value <
      0.001). Results from the Cox regression models suggest that the end of the follow
      up was reached by sows of the treatment group at about twice the rate of sows of
      the control group (model 2, Hazard Ratiotreatment = 2.27; 95%CI: 1.56-3.24).

PMID- 25576268
TI  - Effect of homeopathic Lycopodium clavatum on memory functions and cerebral blood
      flow in memory-impaired rats.
AB  - BACKGROUND: Lycopodium clavatum (Lyc) is a widely used homeopathic medicine for
      the liver, urinary and digestive disorders. Recently, acetyl cholinesterase
      (AchE) inhibitory activity has been found in Lyc alkaloid extract, which could be
      beneficial in dementia disorder. However, the effect of Lyc has not yet been
      explored in animal model of memory impairment and on cerebral blood flow. AIM:
      The present study was planned to explore the effect of Lyc on learning and memory
      function and cerebral blood flow (CBF) in intracerebroventricularly (ICV)
      administered streptozotocin (STZ) induced memory impairment in rats. MATERIALS
      AND METHODS: Memory deficit was induced by ICV administration of STZ (3 mg/kg) in
      rats on 1st and 3rd day. Male SD rats were treated with Lyc Mother Tincture (MT)
      30, 200 and 1000 for 17 days. Learning and memory was evaluated by Morris water
      maze test on 14th, 15th and 16th day. CBF was measured by Laser Doppler flow
      meter on 17th day. RESULTS: STZ (ICV) treated rats showed impairment in learning
      and memory along with reduced CBF. Lyc MT and 200 showed improvement in learning
      and memory. There was increased CBF in STZ (ICV) treated rats at all the
      potencies of Lyc studied. CONCLUSION: The above study suggests that Lyc may be
      used as a drug of choice in condition of memory impairment due to its beneficial
      effect on CBF.

PMID- 25576267
TI  - Effects of homeopathic Anax imperator on behavioural and pain models in mice.
AB  - BACKGOUND: Homeopathy is a medical theory and practice that asserts that disease
      can be cured by remedies that produce symptoms in a healthy person similar to
      those suffered by a patient with a malady. METHODS: The aim of this study was to
      investigate effects of homeopathic Anax imperator (dragonfly) (Anax-i 30c and
      Anax-i 200c) in the forced swim test (FST), elevated plus-maze (EPM) test, hot
      plate (HP) test and open field test and examined NPY1 receptor expression, in
      naive mice. RESULTS: In the FST, treatment with Anax-i 30c or Anax-i 200c
      significantly diminished immobility time while in EPM test, Anax-i 200c increased
      the percentage of time spent in open arms as well as the percentage of open
      arm/total arms. In the HP test, Anax-i 30c or Anax-i 200c decreased the total
      time mice spent licking their hind paws while in open field test, treatment with
      Anax-i 200c increased the total distance and speed mice traveled compared to the
      control group. Three weeks of daily injections with Anax-i 30c or Anax-i 200c
      caused significant weight loss in mice. Anax-i 30c or Anax-i 200c treatment
      significantly decreased NPY1 receptor expression, and Anax-i 30c also decreased
      NPY2 receptor expression. CONCLUSION: These results suggest that the homeopathic
      Anax-i exerts antidepressant, anxiolytic and analgesic-like effects and causes
      hyperlocomotion and weight loss.

PMID- 25576269
TI  - Hepatoprotective effect of Lycopodium clavatum 30CH on experimental model of
      paracetamol-induced liver damage in rats.
AB  - INTRODUCTION: Homeopathic Lycopodium clavatum is indicated for disorders of the
      digestive system and its accessory organs, including atony of the liver and liver
      tissue failure. Tis suggests that it may have action on drug-induced hepatitis,
      as occurs in paracetamol overdose. PURPOSE: To evaluate the effectiveness of
      Lycopodium clavatum 30C (Lyc) as a hepatoprotector against liver damage
      experimentally induced by paracetamol (Pct) in Wistar rats. METHODOLOGY: Thirty
      animals subdivided into 6 groups were used. Animals from the treated groups were
      pretreated for 8 days with Lyc 30c (0.25 ml/day), receiving a dose of 3 g/kg of
      Pct on the 8th day. A positive control group received similar treatment,
      replacing Lyc 30c with 30% ethanol and a negative control received only 30%
      ethanol. After 24 and 72 h, the animals were sacrificed for tissue and blood
      sample collection. Subsequently, enzyme serum measurements indicative of liver
      damage (aspartate-aminotransferase (AST) and Alanine-aminotransferase (ALT)) and
      liver histological and morphometric analyses were performed. RESULTS:
      Pretreatment with Lyc 30c reduced hepatic lesions produced by Pct overdose as
      evidenced by a significant reduction (p < 0.05) in ALT levels in the LyP 24h
      group (901.04 +/- 92.05 U/l) compared to the respective control group (1866.28 +/
      585.44 U/l), promoted a significant decrease in the number of acinar zone 1
      affected by necrosis and inflammatory infiltration (15.46 +/- 13.86 clr/cm(2) in
      LyP72 for 73.75 +/- 16.60 clr/cm(2) in PC72), and inhibition of 1,2-glycol
      (glycogen) depletion in zone 3 (a significant reduction in Lyc 72 h group animals
      in comparison to the control group). Significant changes concerning the
      development of fibrosis or alterations in transaminase levels were not observed
      after 72 h. CONCLUSION: Lyc 30c exerted a moderate hepatoprotective effect on
      acute Pct-induced hepatitis, mainly shown by a histological decrease in necrosis
      and inflammatory foci, preserved glycogen and other 1,2-glycols in zone 3 and
      reduced serum levels of ALT and AST.

PMID- 25576270
TI  - DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by Ruta
      graveolens in human colon cancer cells.
AB  - In the present study, we investigated the anti-cancer effect of various potencies
      of Ruta graveolens (Ruta) on COLO-205 cell line, as evidenced by cytotoxicity,
      migration, clonogenecity, morphological and biochemical changes and modification
      in the levels of genes associated with apoptosis and cell cycle. On treatment of
      COLO-205 cells maximal effects were seen with mother tincture (MT) and 30C
      potencies, wherein decrease in cell viability along with reduced clonogenecity
      and migration capabilities were noted. In addition morphological and biochemical
      alterations such as nuclear changes (fragmented nuclei with condensed chromatin)
      and DNA ladder-like pattern (increased amount of fragmented DNA) in COLO-205
      cells indicating apoptotic related cell death were seen. The expression of
      apoptosis and cell-cycle related regulatory genes assessed by reverse
      transcriptase-PCR revealed an up-regulation of caspase 9, caspase-3, Bax, p21 and
      p27 expression and down-regulation of Bcl-2 expression in treated cells. The mode
      of cell death was suggestive of intrinsic apoptotic pathway along with cell cycle
      arrest at the G2/M of the cell cycle. Our findings indicate that phytochemicals
      present in Ruta showed potential for natural therapeutic product development for
      colon carcinoma. 

PMID- 25576271
TI  - Trypanosoma cruzi: biotherapy made from trypomastigote modulates the inflammatory
      response.
AB  - This study evaluates the effect of Trypanosoma cruzi biotherapy 17dH (BIOT) on
      mice of different ages, infected with the protozoa concerned. METHOD: Performing
      a blind, controlled, randomized by drawing experiment, 110 animals four or eight
      week-old, Swiss, male mice were divided into infected control treated
      hydroalcoholic 7% (CI-4 = 34 or CI-8 = 21 animals) and infected control treated
      with biotherapy 17dH-0.2 mL/animal/20 consecutive days/oral regimen (BIOT-4 = 33
      or BIOT-8 = 21 animals). Animals were inoculated intraperitoneally with 1400
      trypomastigote, T. cruzi Y-strain. Parasitological, immunological and
      histopathologic parameters were evaluated statistically, using Statistica-8.0 and
      R 3.0.2 program to analysis of survival. The study was approved by the Ethics
      Committee for Animal Experimentation/UEM. RESULTS: Four-week-old mice showed no
      statistical difference in parasitemia (P = 0.5718) between the treated and
      control group. Eight-week-old mice from the treated group had a higher parasite
      peak (P = 0.0424) and higher parasitemia (P < 0.005) than the control. To both
      groups of 4 and 8 weeks of age, treated or untreated, survival of mice was higher
      in the treated group than in the control, although it was not statistically
      significant (p-value = 0.32, 0.55 respectively). Four-week-old mice displayed a
      spleen section with a number of amastigote nests significantly higher in BIOT-4
      than CI-4 (P = 0.01). In eight-week-old mice the number of amastigote nests (P <
      0.001) and inflammatory foci (P < 0.06-10% significance) in the liver section
      were smaller in BIOT-8 than CI-8. Spleen giant cells were significantly higher in
      CI-8 than in BIOT-8 (P < 0.01). Eight-week-old animals treated with biotherapy
      showed higher parasitemia and lower tissue parasitism. Opposite pattern was
      observed in four-week-old animals. CONCLUSION: There is a difference of high
      diluted medication effect in four and eight-week-old mice. In the group of
      animals 8 weeks the immunomodulatory effect seems to have been higher. Hence,
      treatment with the medicine produced from T. cruzi modulates the inflammatory
      response with increased apoptosis and decreased serum levels of TGF-beta.

PMID- 25576272
TI  - Homeopathic treatment of multimorbid patients: a prospective outcome study with
      polarity analysis.
AB  - BACKGROUND: The treatment of multimorbid patients who have a combination of three
      or more concurrent complaints is one of the core competencies of homeopathy. In
      this article we introduce the application of polarity analysis (PA) in
      multimorbidity. PA came to prominence through the Swiss homeopathic ADHD double
      blind study, which successfully demonstrated a significant difference between
      highly dilute homeopathic remedies and placebo. PA enables homeopaths to
      calculate a relative healing probability, based on Boenninghausen's grading of
      polar symptoms. After its evaluation in the treatment of a variety of acute and
      chronic disease, which showed improved results compared to a conventional
      homeopathic approach, it was a challenge to test PA with multimorbid patients.
      Since such patients almost invariably have a multiple symptoms, the question was
      whether we can nevertheless successfully use Polarity Analysis or whether the
      method is rendered ineffective by the multitude of symptoms. METHODS: We treated
      50 multimorbid patients with PA and prospectively followed them over one year.
      RESULTS: 43 patients (86%) completed the observation period, achieving an average
      improvement of 91% in their initial symptoms. Six patients dropped out, and one
      did not achieve an improvement of 80%, and was therefore also counted as a
      treatment failure. The cost of homeopathic treatment was 41% of projected
      equivalent conventional treatment. CONCLUSIONS: Polarity Analysis is an effective
      method for treating multimorbidity. The multitude of symptoms does not prevent
      the method from achieving good results. Homeopathy may be capable of taking over
      a considerable proportion of the treatment of multimorbid patients, at lower
      costs than conventional medicine.

PMID- 25576273
TI  - Primary endpoint results of the OMEGA Study: One-year clinical outcomes after
      implantation of a novel platinum chromium bare metal stent.
AB  - BACKGROUND/PURPOSE: Bare metal stents (BMS) have similar rates of death and
      myocardial infarction (MI) compared to drug-eluting stents (DES). DES lower
      repeat revascularization rates compared to BMS, but may have higher rates of late
      stent thrombosis (ST) potentially due to impaired endothelialization requiring
      longer dual anti-platelet therapy (DAPT). OMEGA evaluated a novel BMS designed to
      have improved deliverability and radiopacity, in comparison to currently
      available platforms. METHODS/MATERIALS: OMEGA was a prospective, multicenter,
      single-arm study enrolling 328 patients at 37 sites (US and Europe). Patients
      received the OMEGA stent (bare platinum chromium element stent) for the treatment
      of de novo native coronary artery lesions (<=28 mm long; diameter >=2.25 mm to
      <=4.50mm). The primary endpoint was 9-month target lesion failure (TLF: cardiac
      death, target vessel-related MI, target lesion revascularization [TLR]) compared
      to a prespecified performance goal (PG) based on prior generation BMS. All major
      cardiac events were independently adjudicated. DAPT was required for a minimum of
      1 month post procedure. RESULTS: In the OMEGA study, the mean age was 65; 17% had
      diabetes mellitus. The primary endpoint was met; 9 month TLF rate was 11.5%, and
      the upper 1-sided 95% confidence bound of 14.79% was less than the prespecified
      PG of 21.2% (p<0.0001). One-year event rates were low including a TLF rate of
      12.8% and an ST rate of 0.6% at 12 months. CONCLUSIONS: One-year outcomes of
      OMEGA show low rates of TLF, revascularization and ST. This supports safety and
      efficacy of the OMEGA BMS for the treatment of coronary artery disease.

PMID- 25576274
TI  - Patient radiation exposure in right versus left trans-radial approach for
      coronary procedures.
AB  - OBJECTIVES: The aim of this study was to compare radiation exposure, assessed by
      dose-area product (DAP), in right trans-radial approach (RR) versus left trans
      radial approach (LR) for coronary procedures. BACKGROUND: In LR the catheter
      course is more similar to trans-femoral approach, thus allowing an easier
      negotiation of coronary ostia which, in turn, might translate into reduced
      fluoroscopy time (FT) and radiation exposure as compared to RR. METHODS: We
      retrospectively selected diagnostic and interventional procedures (PCI) performed
      by RR or LR at our center from May 2009 to May 2014. We only included in the
      analysis the procedures in which DAP values were available. RESULTS: We analyzed
      1464 procedures, 1175 of which performed by RR (80.3%) and 289 by LR (19.7%).
      Median DAP values were significantly higher in RR as compared to LR for
      diagnostic and interventional procedures (4482 vs. 3540 cGy.cm(2) and 11523 vs.
      10086 cGy.cm(2), respectively; p < 0.05). No significant differences were
      observed in FT and in contrast volume (CV). In the propensity-matched cohort,
      consisting of 269 procedures for each group, no significant differences between
      LR and RR were observed in median DAP values for both diagnostic and
      interventional procedures (3990 vs. 3542 cGy.cm(2) and 9964 vs. 10216 cGy.cm(2),
      respectively; p = ns); FT and CV were also similar. At multiple linear regression
      analysis laterality of trans-radial approach was not associated with DAP.
      CONCLUSIONS: In an experienced trans-radial center LR is not associated with a
      reduction in radiation exposure, FT or CV as compared to RR.

PMID- 25576275
TI  - Implications of climate and land-use change for landscape processes,
      biodiversity, ecosystem services, and governance.
AB  - This introduction to the Special Issue summarizes the results of 14 scientific
      articles from the interdisciplinary research program Ekoklim at Stockholm
      University, Sweden. In this program, we investigate effects of changing climate
      and land use on landscape processes, biodiversity, and ecosystem services, and
      analyze issues related to adaptive governance in the face of climate and land-use
      change. We not only have a research focus on the 22 650 km(2) Norrstrom catchment
      surrounding lake Malaren in south-central Sweden, but we also conduct research in
      other Swedish regions. The articles presented here show complex interactions
      between multiple drivers of change, as well as feedback processes at different
      spatiotemporal scales. Thus, the Ekoklim program highlights and deals with issues
      relevant for the future challenges society will face when land-use change
      interacts with climate change.

PMID- 25576276
TI  - Screening variability and change of soil moisture under wide-ranging climate
      conditions: Snow dynamics effects.
AB  - Soil moisture influences and is influenced by water, climate, and ecosystem
      conditions, affecting associated ecosystem services in the landscape. This paper
      couples snow storage-melting dynamics with an analytical modeling approach to
      screening basin-scale, long-term soil moisture variability and change in a
      changing climate. This coupling enables assessment of both spatial differences
      and temporal changes across a wide range of hydro-climatic conditions. Model
      application is exemplified for two major Swedish hydrological basins, Norrstrom
      and Pitealven. These are located along a steep temperature gradient and have
      experienced different hydro-climatic changes over the time period of study, 1950
      2009. Spatially, average intra-annual variability of soil moisture differs
      considerably between the basins due to their temperature-related differences in
      snow dynamics. With regard to temporal change, the long-term average state and
      intra-annual variability of soil moisture have not changed much, while inter
      annual variability has changed considerably in response to hydro-climatic changes
      experienced so far in each basin. 

PMID- 25576277
TI  - Regional-scale land-cover change during the 20th century and its consequences for
      biodiversity.
AB  - Extensive changes in land cover during the 20th century are known to have had
      detrimental effects on biodiversity in rural landscapes, but the magnitude of
      change and their ecological effects are not well known on regional scales. We
      digitized historical maps from the beginning of the 20th century over a 1652
      km(2) study area in southeastern Sweden, comparing it to modern-day land cover
      with a focus on valuable habitat types. Semi-natural grassland cover decreased by
      over 96 % in the study area, being largely lost to afforestation and
      silviculture. Grasslands on finer soils were more likely to be converted into
      modern grassland or arable fields. However, in addition to remaining semi-natural
      grassland, today's valuable deciduous forest and wetland habitats were mostly
      grazed grassland in 1900. An analysis of the landscape-level biodiversity
      revealed that plant species richness was generally more related to the modern
      landscape, with grazing management being a positive influence on species
      richness.

PMID- 25576278
TI  - Climate change effects on the Baltic Sea borderland between land and sea.
AB  - Coastal habitats are situated on the border between land and sea, and ecosystem
      structure and functioning is influenced by both marine and terrestrial processes.
      Despite this, most scientific studies and monitoring are conducted either with a
      terrestrial or an aquatic focus. To address issues concerning climate change
      impacts in coastal areas, a cross-ecosystem approach is necessary. Since habitats
      along the Baltic coastlines vary in hydrology, natural geography, and ecology,
      climate change projections for Baltic shore ecosystems are bound to be highly
      speculative. Societal responses to climate change in the Baltic coastal
      ecosystems should have an ecosystem approach and match the biophysical realities
      of the Baltic Sea area. Knowledge about ecosystem processes and their responses
      to a changing climate should be integrated within the decision process, both
      locally and nationally, in order to increase the awareness of, and to prepare for
      climate change impacts in coastal areas of the Baltic Sea. 

PMID- 25576279
TI  - A boreal invasion in response to climate change? Range shifts and community
      effects in the borderland between forest and tundra.
AB  - It has been hypothesized that climate warming will allow southern species to
      advance north and invade northern ecosystems. We review the changes in the
      Swedish mammal and bird community in boreal forest and alpine tundra since the
      nineteenth century, as well as suggested drivers of change. Observed changes
      include (1) range expansion and increased abundance in southern birds, ungulates,
      and carnivores; (2) range contraction and decline in northern birds and
      carnivores; and (3) abundance decline or periodically disrupted dynamics in
      cyclic populations of small and medium-sized mammals and birds. The first warm
      spell, 1930-1960, stands out as a period of substantial faunal change. However,
      in addition to climate warming, suggested drivers of change include land use and
      other anthropogenic factors. We hypothesize all these drivers interacted,
      primarily favoring southern generalists. Future research should aim to
      distinguish between effects of climate and land-use change in boreal and tundra
      ecosystems. 

PMID- 25576281
TI  - Microrefugia: Not for everyone.
AB  - Microrefugia are sites that support populations of species when their ranges
      contract during unfavorable climate episodes. Here, we review and discuss two
      aspects relevant for microrefugia. First, distributions of different species are
      influenced by different climatic variables. Second, climatic variables differ in
      the degree of local decoupling from the regional climate. Based on this, we
      suggest that only species limited by climatic conditions decoupled from the
      regional climate can benefit from microrefugia. We argue that this restriction
      has received little attention in spite of its importance for microrefugia as a
      mechanism for species resilience (the survival of unfavorable episodes and
      subsequent range expansion). Presence of microrefugia will depend on both the
      responses of individual species to local climatic variation and how climate
      forcing factors shape the correlation between local and regional climate across
      space and time. 

PMID- 25576280
TI  - The spatial and temporal components of functional connectivity in fragmented
      landscapes.
AB  - Connectivity is key for understanding how ecological systems respond to the
      challenges of land-use change and habitat fragmentation. Structural and
      functional connectivity are both established concepts in ecology, but the
      temporal component of connectivity deserves more attention. Whereas functional
      connectivity is often associated with spatial patterns (spatial functional
      connectivity), temporal functional connectivity relates to the persistence of
      organisms in time, in the same place. Both temporal and spatial processes
      determine biodiversity responses to changes in landscape structure, and it is
      therefore necessary that all aspects of connectivity are considered together. In
      this perspective, we use a case study to outline why we believe that both the
      spatial and temporal components of functional connectivity are important for
      understanding biodiversity patterns in the present-day landscape, and how they
      can also help us to make better-informed decisions about conserving and restoring
      landscapes and improving resilience to future change. 

PMID- 25576282
TI  - Change in spring arrival of migratory birds under an era of climate change,
      Swedish data from the last 140 years.
AB  - Many migratory bird species have advanced their spring arrival during the latest
      decades, most probably due to climate change. However, studies on migratory
      phenology in the period before recent global warming are scarce. We have analyzed
      a historical dataset (1873-1917) of spring arrival to southern and central Sweden
      of 14 migratory bird species. In addition, we have used relative differences
      between historical and present-day observations (1984-2013) to evaluate the
      effect of latitude and migratory strategy on day of arrival over time. There was
      a larger change in spring phenology in short-distance migrants than in long
      distance migrants. Interestingly, the results further suggest that climate change
      has affected the phenology of short-distance migrants more in southern than in
      central Sweden. The results suggest that the much earlier calculated arrival to
      southern Sweden among short-distance migrants mirrors a change in location of
      wintering areas, hence, connecting migration phenology and wintering range
      shifts. 

PMID- 25576284
TI  - Mapping bundles of ecosystem services reveals distinct types of
      multifunctionality within a Swedish landscape.
AB  - Ecosystem services (ES) is a valuable concept to be used in the planning and
      management of social-ecological landscapes. However, the understanding of the
      determinant factors affecting the interaction between services in the form of
      synergies or trade-offs is still limited. We assessed the production of 16 ES
      across 62 municipalities in the Norrstrom drainage basin in Sweden. We combined
      GIS data with publically available information for quantifying and mapping the
      distribution of services. Additionally, we calculated the diversity of ES for
      each municipality and used correlations and k-means clustering analyses to assess
      the existence of ES bundles. We found five distinct types of bundles of ES
      spatially agglomerated in the landscape that could be explained by regional
      social and ecological gradients. Human-dominated landscapes were highly
      multifunctional in our study area and urban densely populated areas were hotspots
      of cultural services. 

PMID- 25576283
TI  - Climate change, phenology, and butterfly host plant utilization.
AB  - Knowledge of how species interactions are influenced by climate warming is
      paramount to understand current biodiversity changes. We review phenological
      changes of Swedish butterflies during the latest decades and explore potential
      climate effects on butterfly-host plant interactions using the Orange tip
      butterfly Anthocharis cardamines and its host plants as a model system. This
      butterfly has advanced its appearance dates substantially, and its mean flight
      date shows a positive correlation with latitude. We show that there is a large
      latitudinal variation in host use and that butterfly populations select plant
      individuals based on their flowering phenology. We conclude that A. cardamines is
      a phenological specialist but a host species generalist. This implies that
      thermal plasticity for spring development influences host utilization of the
      butterfly through effects on the phenological matching with its host plants.
      However, the host utilization strategy of A. cardamines appears to render it
      resilient to relatively large variation in climate.

PMID- 25576285
TI  - A social-ecological analysis of ecosystem services in two different farming
      systems.
AB  - In this exploratory study we use existing in situ qualitative and quantitative
      data on biophysical and social indicators to compare two contrasting Swedish
      farming systems (low intensity and high intensity) with regard to ecosystem
      service supply and demand of a broad suite of services. We show that the value
      (demand) placed on a service is not necessarily connected to the quantity
      (supply) of the service, most clearly shown for the services recreation,
      biodiversity, esthetic experience, identity, and cultural heritage. To better
      capture this complexity we argue for the need to develop portfolios of indicators
      for different ecosystem services and to further investigate the different aspects
      of supply and demand. The study indicates that available data are often ill
      suited to answer questions about local delivery of services. If ecosystem
      services are to be included in policy, planning, and management, census data need
      to be formatted and scaled appropriately. 

PMID- 25576286
TI  - Predicting climate change effects on wetland ecosystem services using species
      distribution modeling and plant functional traits.
AB  - Wetlands provide multiple ecosystem services, the sustainable use of which
      requires knowledge of the underlying ecological mechanisms. Functional traits,
      particularly the community-weighted mean trait (CWMT), provide a strong link
      between species communities and ecosystem functioning. We here combine species
      distribution modeling and plant functional traits to estimate the direction of
      change of ecosystem processes under climate change. We model changes in CWMT
      values for traits relevant to three key services, focusing on the regional
      species pool in the Norrstrom area (central Sweden) and three main wetland types.
      Our method predicts proportional shifts toward faster growing, more productive
      and taller species, which tend to increase CWMT values of specific leaf area and
      canopy height, whereas changes in root depth vary. The predicted changes in CWMT
      values suggest a potential increase in flood attenuation services, a potential
      increase in short (but not long)-term nutrient retention, and ambiguous outcomes
      for carbon sequestration. 

PMID- 25576287
TI  - Dissecting the ecosystem service of large-scale pollutant retention: The role of
      wetlands and other landscape features.
AB  - Various features of a landscape contribute to the regulating ecosystem service of
      reducing waterborne pollutant loading to downstream environments. At local
      scales, wetlands have been shown to be effective in retaining pollutants. Here,
      we investigate the landscape-scale contribution to pollutant retention provided
      by multiple wetlands. We develop a general analytical model which shows that the
      retention contribution of wetlands and other landscape features is only
      significant if a large fraction of the total waterborne pollutant transport
      passes through them. Next, by means of a statistical analysis of official data,
      we quantify the nutrient retention contribution of wetlands for multiple sub
      catchments in two Swedish Water Management Districts. We compare this with the
      retention contribution of two other landscape features: the waterborne transport
      distance and major lakes. The landscape-scale retention contribution of wetlands
      is undetectable; rather, the other two landscape features account for much of the
      total nutrient retention. 

PMID- 25576288
TI  - Closing the collaborative gap: Aligning social and ecological connectivity for
      better management of interconnected wetlands.
AB  - Understanding how governance structures align to ecological processes in a
      landscape is critical for effective management of ecological resources.
      Ecological resources are not independent from each other, instead they are
      interconnected, and their well-being is often critically dependent on upholding
      ecological connectivity, especially in times of change and disturbances.
      Coordination and collaboration among managing actors, each managing their own
      piece of the puzzle, is therefore essentially a requirement for effective
      management. We present a conceptual model that includes ecological resources,
      managing and coordinating actors, along with an explicit representation on how
      all these entities are connected to each other. We apply this model to 25
      municipalities that manage 408 wetlands in central Sweden. The study shows a good
      social and ecological alignment, however with a high prevalence for coordination
      through third parties. We discuss this pattern emergence, its potential
      implications, and examine which municipalities adopt these coordinating
      functions. 

PMID- 25576289
TI  - Anticipatory governance for social-ecological resilience.
AB  - Anticipation is increasingly central to urgent contemporary debates, from climate
      change to the global economic crisis. Anticipatory practices are coming to the
      forefront of political, organizational, and citizens' society. Research into
      anticipation, however, has not kept pace with public demand for insights into
      anticipatory practices, their risks and uses. Where research exists, it is deeply
      fragmented. This paper seeks to identify how anticipation is defined and
      understood in the literature and to explore the role of anticipatory practice to
      address individual, social, and global challenges. We use a resilience lens to
      examine these questions. We illustrate how varying forms of anticipatory
      governance are enhanced by multi-scale regional networks and technologies and by
      the agency of individuals, drawing from an empirical case study on regional water
      governance of Malaren, Sweden. Finally, we discuss how an anticipatory approach
      can inform adaptive institutions, decision making, strategy formation, and
      societal resilience. 

PMID- 25576291
TI  - In situ atomic scale mechanical microscopy discovering the atomistic mechanisms
      of plasticity in nano-single crystals and grain rotation in polycrystalline
      metals.
AB  - In this review, we briefly introduce our in situ atomic-scale mechanical
      experimental technique (ASMET) for transmission electron microscopy (TEM), which
      can observe the atomic-scale deformation dynamics of materials. This in situ
      mechanical testing technique allows the deformation of TEM samples through a
      simultaneous double-tilt function, making atomic-scale mechanical microscopy
      feasible. This methodology is generally applicable to thin films, nanowires
      (NWs), tubes and regular TEM samples to allow investigation of the dynamics of
      mechanically stressed samples at the atomic scale. We show several examples of
      this technique applied to Pt and Cu single/polycrystalline specimens. The in situ
      atomic-scale observation revealed that when the feature size of these materials
      approaches the nano-scale, they often exhibit "unusual" deformation behaviours
      compared to their bulk counterparts. For example, in Cu single-crystalline NWs,
      the elastic-plastic transition is size-dependent. An ultra-large elastic strain
      of 7.2%, which approaches the theoretical elasticity limit, can be achieved as
      the diameter of the NWs decreases to ~6 nm. The crossover plasticity transition
      from full dislocations to partial dislocations and twins was also discovered as
      the diameter of the single-crystalline Cu NWs decreased. For Pt nanocrystals
      (NC), the long-standing uncertainties of atomic-scale plastic deformation
      mechanisms in NC materials (grain size G less than 15 nm) were clarified. For
      larger grains with G<~10 nm, we frequently observed movements and interactions of
      cross-grain full dislocations. For G between 6 and 10 nm, stacking faults
      resulting from partial dislocations become more frequent. For G<~6 nm, the
      plasticity mechanism transforms from a mode of cross-grain dislocation to a
      collective grain rotation mechanism. This grain rotation process is mediated by
      grain boundary (GB) dislocations with the assistance of GB diffusion and
      shuffling. These in situ atomic-scale images provide a direct demonstration that
      grain rotation, through the evolution of the misorientation angle between
      neighbouring grains, can be quantitatively assessed by the dislocation content
      within the grain boundaries. In combination with the revolutionary Cs-corrected
      sub-angstrom imaging technologies developed by Urban et al., the opportunities
      for experimental mechanics at the atomic scale are emerging.

PMID- 25576290
TI  - Primary mediastinal seminomas: a comprehensive immunohistochemical study with a
      focus on novel markers.
AB  - Primary mediastinal seminomas are unusual tumors that can present in a pure form
      or as part of a mixed germ cell tumor. Contrary to testicular seminomas, little
      is known about the expression of novel immunohistochemical markers in mediastinal
      seminomas. This study investigates the immunohistochemical features of these
      tumors with a focus on novel markers. Thirty-two cases of primary mediastinal
      seminomas were reviewed; and representative whole-tissue sections were selected
      for immunohistochemical studies using antibodies directed against high molecular
      weight cytokeratin 5/6 (CK5/6), low molecular weight cytokeratin (CAM5.2),
      octamer-binding transcription factor 3/4 (OCT3/4), spalt-like transcription
      factor 4 (SALL4), GATA binding protein 3 (GATA-3), sry-related HMG box 2 (SOX2),
      SOX17, human T cell leukemia/lymphoma 1 (TCL1), glypican 3, melanoma associated
      antigen C2 (MAGEC2), and paired box gene 8 (Pax8). The percentage of positive
      tumor cells as well as the intensity of staining was evaluated and scored. Thirty
      one cases (97%) expressed SOX17, whereas 29 cases (91%) were positive for OCT3/4
      and SALL4, respectively. Twenty-eight cases (88%) expressed MAGEC2 and CAM5.2,
      respectively. Two cases (6%) were positive for Pax8, and a single case (3%) was
      positive for TCL1. None of the cases stained with CK5/6, GATA-3, SOX2, or
      glypican 3. Similar to testicular seminomas, mediastinal seminomas show
      consistent expression of OCT3/4, SALL4, SOX17, and MAGEC2 and are negative for
      SOX2, glypican 3, GATA-3, and CK5/6. Pax8 positivity is only inconsistently
      identified in mediastinal seminomas. Contrary to their testicular counterparts,
      mediastinal tumors show diffuse expression of low-molecular-weight cytokeratin in
      up to 90% of cases and are commonly negative for TCL1. Although there is some
      immunohistochemical overlap between testicular and mediastinal seminomas,
      considerable differences also exist and should be acknowledged when dealing with
      these tumors. 

PMID- 25576292
TI  - Comparative activities of vancomycin, tigecycline and rifampin in a rat model of
      methicillin-resistant Staphylococcus aureus osteomyelitis.
AB  - OBJECTIVES: Implant-associated methicillin-resistant Staphylococcus aureus (MRSA)
      infections are challenging to treat. We compared antimicrobial activities in a
      rat model of chronic osteomyelitis in the context of retention of the foreign
      body without debridement. METHODS: MRSA was inoculated into the proximal tibia
      and a wire implanted. Four weeks after infection, treatment with vancomycin 50
      mg/kg every 12 h, tigecycline 14 mg/kg every 12 h, rifampin 25 mg/kg every 12 h,
      or the combination of vancomycin or tigecycline plus rifampin was administered
      intraperitoneally for 21 days. RESULTS: MRSA was cultured from all tibias in the
      control group (median, 6.06 log10 CFU/g bone). Median bacterial counts (log10
      CFU/g) at 48 h post-treatment were 6.16 for vancomycin (p = 0.753), 2.29 for
      vancomycin plus rifampin (p < 0.001), 5.90 for tigecycline (p = 0.270), 0.10 for
      tigecycline plus rifampin (p < 0.001), and 0.91 for rifampin (p = 0.044)
      treatment. Three deaths were observed in the tigecycline plus rifampin group.
      Median bacterial counts (log10 CFU/g) at two weeks post-treatment were 5.65 for
      vancomycin (p = 0.6), 4.05 for vancomycin plus rifampin (p = 0.105), 5.68 for
      tigecycline (p = 0.401), 4.05 for tigecycline plus rifampin (p = 0.028), and 5.98
      for rifampin (p = 0.297) treatment. CONCLUSIONS: Tigecycline plus rifampin
      resulted in a significant bacterial count decrease, an effect more prominent at
      48 h than two weeks after treatment completion. Tigecycline was not well
      tolerated at the dose studied.

PMID- 25576293
TI  - Ten-year mortality risk predictors after primary total knee arthroplasty for
      osteoarthritis.
AB  - PURPOSE: To determine predictors of mortality up to 10 post-operative years.
      METHODS: A cohort of 1,569 consecutive patients who underwent primary cementless
      total knee arthroplasty (TKA) for osteoarthritis was prospectively evaluated.
      Patient mortality was compared to the general population using standardized
      mortality ratios (SMR). The effects on patient mortality and surgical data, as
      well as post-operative outcomes, were analysed using Cox regression analysis.
      RESULTS: The 10-year survival was 88.9% in females and 73.4% in males (p =
      0.001). The SMR were higher for females under 50 years (213.1%) and for males
      over 70 years (170.5%). Aged 70 or older and male gender were predictive for
      mortality in any post-operative time. Lengthening of the follow-up time showed
      different patterns of other risk mortality factors. Within 8 years, high Charlson
      index, poorer post-operative clinical status, and quality of life were also
      associated with an increased mortality risk, and obesity was protective factor.
      However, 10-year mortality was only associated with age, female gender, post
      operative walking disability, and increasing post-operative WOMAC pain score.
      CONCLUSION: In this study, patient-related factors that can help identify
      patients at risk were only age and gender, while recovery of walking ability,
      WOMAC pain, and SF-12 mental component were important survival factors among post
      operative factors. This study identified important patient-related predictors of
      mortality after TKA, which may be useful in order to inform the patients of the
      potential risks. LEVEL OF EVIDENCE: IV.

PMID- 25576294
TI  - Management of crizotinib therapy for ALK-rearranged non-small cell lung
      carcinoma: an expert consensus.
AB  - Within 4 years of the discovery of anaplastic lymphoma kinase (ALK)
      rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor
      crizotinib gained US and European approval for the treatment of advanced ALK
      positive NSCLC. This was due to the striking response data observed with
      crizotinib in phase I and II trials in patients with ALK-positive NSCLC, as well
      as the favorable tolerability and safety profile observed. Recently published
      phase III data established crizotinib as a new standard of care for this NSCLC
      molecular subset. A consequence of such rapid approval, however, is the limited
      clinical experience and relative paucity of information concerning optimal
      therapy management. In this review, we discuss the development of crizotinib and
      the clinical relevance of its safety profile, examining crizotinib-associated
      adverse events in detail and making specific management recommendations.
      Crizotinib-associated adverse events were mostly mild to moderate in severity in
      clinical studies, and appropriate monitoring and supportive therapies are
      considered effective in avoiding the need for dose interruption or reduction in
      most cases. Therapy management of patients following disease progression on
      crizotinib is also discussed. Based on available clinical data, it is evident
      that patients may have prolonged benefit from crizotinib after Response
      Evaluation Criteria in Solid Tumors-defined disease progression, and crizotinib
      should be continued for as long as the patient derives benefit.

PMID- 25576295
TI  - Genetic variants in genes of tricarboxylic acid cycle key enzymes are associated
      with prognosis of patients with non-small cell lung cancer.
AB  - INTRODUCTION: Non-small cell lung cancer (NSCLC) is characterized by poor
      prognosis and only a few molecular markers may be potentially used to predict the
      outcome. Metabolic reprogramming is a hallmark of cancer, including the
      alterations of tricarboxylic acid (TCA) cycle key enzymes. However, the
      significance of single nucleotide polymorphisms (SNPs) in genes encoding these
      key enzymes has not been investigated in NSCLC. PATIENTS AND METHODS: In this
      study, we genotyped 18 potentially functional SNPs in 7 genes belonging to 3 TCA
      cycle enzyme families (SDH, FH and IDH) using Sequenom iPLEX genotyping system in
      a cohort of 500 NSCLC patients. Multivariate Cox proportional hazards model and
      Kaplan-Meier curve were used for the survival analysis. RESULTS: Our results
      showed that SDHC gene: SNP rs12064957, IDH2 gene: SNP rs11540478 and FH gene: SNP
      rs1414493 were associated with overall survival (OS) and SDHA gene: SNP
      rs13173911, IDH2 gene: SNP rs4932158 were associated with recurrence-free
      survival (RFS) of NSCLC patients. Unfavorable genotypes of these SNPs showed a
      significant cumulative effect on OS and RFS of NSCLC patients (both P<0.001).
      Furthermore, survival tree analysis indicated that FH: rs1414493 was the primary
      risk factor contributing to OS of NSCLC patients and the IDH2: rs4932158 was the
      primary risk factor contributing to RFS of NSCLC patients. CONCLUSION: Our data
      suggest that SNPs in TCA cycle key enzyme genes may serve as potential biomarkers
      to predict the outcomes of NSCLC. Further studies with different ethnicities are
      needed to validate our findings and generalize their clinical utility.

PMID- 25576296
TI  - Matrine protects neuro-axon from CNS inflammation-induced injury.
AB  - Neuro-axonal injury in the central nervous system (CNS) is one of the major
      pathological hallmarks of experimental autoimmune encephalomyelitis (EAE), an
      experimental model of multiple sclerosis (MS). Matrine (MAT), a quinolizidine
      alkaloid derived from the herb Radix Sophorae Flave, has recently been shown to
      effectively suppress EAE through an anti-inflammatory mechanism. However, whether
      MAT can also protect myelin/axons from damage is not known. In the present study
      we show that, while untreated rats developed severe clinical disease, CNS
      inflammatory demyelination, and axonal damage, these clinical and pathological
      signs were significantly reduced by MAT treatment. Consistently, MAT treatment
      reduced the concentration of myelin basic protein in serum and downregulated
      expression of beta-amyloid (Abeta) and B-site APP cleaving enzyme 1 (BACE-1) in
      the CNS. Further, the CNS of MAT-treated rats exhibited increased expression of
      brain-derived neurotrophic factor (BDNF), an important factor for neuronal
      survival and axonal growth. Together, these results demonstrate that MAT
      effectively prevented neuro-axonal injury, which can likely be attributed to
      inhibiting risk factors such as BACE-1 and upregulating neuroprotective factors
      such as BDNF. We conclude that this novel natural reagent, MAT, which effectively
      protects neuro-axons from CNS inflammation-induced damage, could be a potential
      candidate for the treatment of neurodegenerative diseases such as MS. 

PMID- 25576298
TI  - Statures in Han populations of China.

PMID- 25576297
TI  - Sodium valproate ameliorates diabetes-induced fibrosis and renal damage by the
      inhibition of histone deacetylases in diabetic rat.
AB  - Recent reports emphasize the contribution of histone deacetylases (HDACs) in the
      pathogenesis of diabetic renal injury and fibrosis. Valproic acid (VPA) is a
      first-line drug used for the treatment of epilepsy and migraine as well as
      established as a HDAC inhibitor. The present study was aimed to evaluate the anti
      fibrotic and renoprotective effects of VPA in diabetic nephropathy (DN). Diabetes
      was induced by single injection of STZ (50mg/kg), whereas VPA at the doses of 150
      and 300mg/kg/day was administered for 8 consecutive weeks by oral route in
      Sprague Dawley rats. The renal injuries and fibrosis were assessed by histology,
      fibrosis specific staining and fibroblast activation by a transmission electron
      microscope, while expression of proteins of interest was evaluated by western
      blotting and immunohistochemistry. VPA treatment ameliorated the histological
      alterations as well as fibrosis, and decreased the expression of TGF-beta1, CTGF,
      alpha-SMA, fibronectin, collagen I, COX-2, ICAM-1 and HDAC4/5/7. Further, VPA
      treatment significantly increased histone H3 acetylation and MMP-2 expression.
      The present study clearly established that VPA treatment ameliorates the renal
      injury and fibrosis in diabetic kidney by preventing the myofibroblast activation
      and fibrogenesis by HDAC inhibition and associated mechanisms, thereby improving
      the profibrotic and anti-fibrotic protein balance. 

PMID- 25576299
TI  - Impact of insect-resistant GM rice on pesticide use and farmers' health in China.
AB  - The economic benefits of insect-resistant genetically modified (GM) crops have
      been well documented, but the impact of such crops and the consequent reduction
      in pesticide use on farmers' health remains largely unknown. Through the analysis
      of the data collected from the physical examination from farmers in China, we
      show that GM rice significantly reduces pesticide use and the resultant not only
      visible but also invisible adverse effects on farmers' neurological,
      hematological, and electrolyte system. Hence, the commercialization of GM rice is
      expected to improve the health of farmers in developing countries, where
      pesticide application is necessary to mitigate crop loss. 

PMID- 25576300
TI  - Internet gaming disorder, social network disorder and laterality: handedness
      relates to pathological use of social networks.
AB  - The internet age bears new challenges that include health risks. It is agreed
      that excessive internet use may reach pathological levels. However, the concept
      of internet addiction lacks specificity and, therefore, warrants studies on its
      diagnostic and etiologic classification. This study was conducted to characterize
      the novel DSM-5 criteria for internet gaming disorder and the adapted criteria
      for the "social network disorder". Based on the established association of
      handedness and substance use disorders, we also explored whether internet use
      related to laterality. For this study, 3,287 volunteers participated in the
      online survey and gave particulars concerning their internet use in general,
      internet gaming and use of social networks, laterality markers (hand, foot, eye,
      ear, rotational preference in gymnastics, and head turning asymmetry) and health
      status. Of the participants, 1.1 % fulfilled the criteria for internet gaming
      disorder, and 1.8 % fulfilled the criteria for social network disorder. The
      applied criteria were highly correlated with the time spent on the respective
      internet activities (p < 4 * 10(-56)). The analyses of comorbidity and working
      hours support the thresholds of 5/9 criteria and >=30 h/week spent on the
      internet for the classification as pathological (p < 5 * 10(-2)). Moreover, we
      found that left-handedness related to more affirmed criteria and longer times
      spent on social networks (p <= 4 * 10(-2)). The provided criteria proved to be
      user-friendly, comprehensible and well accepted. The results contribute to a
      better understanding of pathological internet gaming and social network use and
      provide evidence that biological markers of substance use disorders are involved
      in internet addiction.

PMID- 25576303
TI  - Medicinal use of cannabis in Europe: the fact that more countries legalize the
      medicinal use of cannabis should not become an argument for unfettered and
      uncontrolled use.

PMID- 25576301
TI  - Mass spectrometry of human leukocyte antigen class I peptidomes reveals strong
      effects of protein abundance and turnover on antigen presentation.
AB  - HLA class I molecules reflect the health state of cells to cytotoxic T cells by
      presenting a repertoire of endogenously derived peptides. However, the extent to
      which the proteome shapes the peptidome is still largely unknown. Here we present
      a high-throughput mass-spectrometry-based workflow that allows stringent and
      accurate identification of thousands of such peptides and direct determination of
      binding motifs. Applying the workflow to seven cancer cell lines and primary
      cells, yielded more than 22,000 unique HLA peptides across different allelic
      binding specificities. By computing a score representing the HLA-I sampling
      density, we show a strong link between protein abundance and HLA-presentation (p
      < 0.0001). When analyzing overpresented proteins - those with at least fivefold
      higher density score than expected for their abundance - we noticed that they are
      degraded almost 3 h faster than similar but nonpresented proteins (top 20%
      abundance class; median half-life 20.8h versus 23.6h, p < 0.0001). This validates
      protein degradation as an important factor for HLA presentation. Ribosomal,
      mitochondrial respiratory chain, and nucleosomal proteins are particularly well
      presented. Taking a set of proteins associated with cancer, we compared the
      predicted immunogenicity of previously validated T-cell epitopes with other
      peptides from these proteins in our data set. The validated epitopes indeed tend
      to have higher immunogenic scores than the other detected HLA peptides.
      Remarkably, we identified five mutated peptides from a human colon cancer cell
      line, which have very recently been predicted to be HLA-I binders. Altogether, we
      demonstrate the usefulness of combining MS-analysis with immunogenesis prediction
      for identifying, ranking, and selecting peptides for therapeutic use. 

PMID- 25576304
TI  - Bypass surgery is more cost-effective than percutaneous coronary interventions
      for most patients with multivessel or left main coronary artery disease.

PMID- 25576305
TI  - Purification and characterization of the membrane-bound quinoprotein glucose
      dehydrogenase of Gluconacetobacter diazotrophicus PAL 5.
AB  - Acetic acid bacteria oxidize a great number of substrates, such as alcohols and
      sugars, using different enzymes that are anchored to the membrane. In particular,
      Gluconacetobacter diazotrophicus is distinguished for its N2-fixing activity
      under high-aeration conditions. Ga. diazotrophicus is a true endophyte that also
      has membrane-bound enzymes to oxidize sugars and alcohols. Here we reported the
      purification and characterization of the membrane-bound glucose dehydrogenase
      (GDHm), an oxidoreductase of Ga. diazotrophicus. GDHm was solubilized and
      purified by chromatographic methods. Purified GDHm was monomeric, with a
      molecular mass of 86 kDa. We identified the prosthetic group as pyrroloquinoline
      quinone, whose redox state was reduced. GDHm showed an optimum pH of 7.2, and its
      isoelectric point was 6.0. This enzyme preferentially oxidized D-glucose, 2-deoxy
      D-glucose, D-galactose and D-xylose; its affinity towards glucose was ten times
      greater than that of E. coli GDHm. Finally, Ga. diazotrophicus GDHm was capable
      of reducing quinones such as Q 1, Q 2, and decylubiquinone; this activity was
      entirely abolished in the presence of micromolar concentrations of the inhibitor,
      myxothiazol. Hence, our purification method yielded a highly purified GDHm whose
      molecular and kinetic parameters were determined. The possible implications of
      GDHm activity in the mechanism for reducing competitor microorganisms, as well as
      its participation in the respiratory system of Ga. diazotrophicus, are discussed.

PMID- 25576306
TI  - Acid stability of the kinetically stable alkaline serine protease possessing
      polyproline II fold.
AB  - The kinetically stable alkaline serine protease from Nocardiopsis sp.; NprotI,
      possessing polyproline II fold (PPII) was characterized for its pH stability
      using proteolytic assay, fluorescence and Circular Dichroism (CD) spectroscopy,
      and Differential Scanning Calorimetry (DSC). NprotI was found to be functionally
      stable when incubated at pH 1.0, even after 24 h, while after incubation at pH
      10.0, drastic loss in the activity was observed. The enzyme showed enhanced
      activity after incubation at pH 1.0 and 3.0, at higher temperature (50-60 
      degrees C). NprotI maintained the overall PPII fold in broad pH range as seen
      using far UV CD spectroscopy. The PPII fold of NprotI incubated at pH 1.0
      remained fairly intact up to 70  degrees C. Based on the isodichroic point and Tm
      values revealed by secondary structural transitions, different modes of thermal
      denaturation at pH 1.0, 5.0 and 10.0 were observed. DSC studies of NprotI
      incubated at acidic pH (pH 1.0-5.0) showed Tm values in the range of 74-76 
      degrees C while significant decrease in Tm (63.8  degrees C) was observed at pH
      10.0. NprotI could be chemically denatured at pH 5.0 (stability pH) only with
      guanidine thiocynate. NprotI can be classified as type III protein among the
      three acid denatured states. Acid tolerant and thermostable NprotI can serve as a
      potential candidate for biotechnological applications.

PMID- 25576307
TI  - Evaluating the importance of the tentorial angle in the paramedian
      supracerebellar-transtentorial approach for selective amygdalohippocampectomy.
AB  - OBJECTIVE: A challenging step of the paramedian supracerebellar-transtentorial
      approach is to expose the anterior portion of the mediobasal-temporal region
      (MTR), a step that seems most affected by the steepness of the tentorium. The
      objective of this study was to define magnetic resonance imaging measurements
      that can predict the level of challenge in exposing the anterior portion of the
      MTR. METHODS: Cranial magnetic resonance imaging studies of 100 healthy
      individuals were examined. The tentorial and occipital angles were measured, and
      the amount of brain tissue that remained hidden on the microscopic view in front
      of the petrous apex was indirectly estimated. These measurements were
      statistically compared with the cephalic index of each person. RESULTS: The mean
      values for the tentorial and occipital angles were 42 degrees  (range 25 degrees 
      53 degrees ) and 98 degrees  (range 69 degrees -122 degrees ), respectively. The
      results proved that the higher the tentorial angle, the higher the occipital
      angle and the greater the amount of hidden brain tissue. Of 100 persons, 3 (3%)
      were found to be dolichocephalic, 23 (23%) were mesocephalic, and 74 (74%) were
      brachycephalic. Statistical analysis proved that individuals with a
      dolichocephalic cranial shape have lower tentorial and occipital angles.
      CONCLUSIONS: The results provide strong evidence proving that the lesser the
      tentorial and occipital angles, the easier the exposure of the anterior portion
      of the MTR during the paramedian supracerebellar-transtentorial approach. The
      tendency of the cranial shape toward dolichocephaly seems to have the same
      practical value in choosing the approach. It is easier to expose the anterior
      portion of the MTR in these individuals.

PMID- 25576308
TI  - CHCHD10 mutations in Italian patients with sporadic amyotrophic lateral
      sclerosis.

PMID- 25576302
TI  - Molecular control of PtdIns(3,4,5)P3 signaling in neutrophils.
AB  - Neutrophils play critical roles in innate immunity and host defense. However,
      excessive neutrophil accumulation or hyper-responsiveness of neutrophils can be
      detrimental to the host system. Thus, the response of neutrophils to inflammatory
      stimuli needs to be tightly controlled. Many cellular processes in neutrophils
      are mediated by localized formation of an inositol phospholipid,
      phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), at the plasma
      membrane. The PtdIns(3,4,5)P3 signaling pathway is negatively regulated by lipid
      phosphatases and inositol phosphates, which consequently play a critical role in
      controlling neutrophil function and would be expected to act as ideal therapeutic
      targets for enhancing or suppressing innate immune responses. Here, we
      comprehensively review current understanding about the action of lipid
      phosphatases and inositol phosphates in the control of neutrophil function in
      infection and inflammation. 

PMID- 25576309
TI  - Reply: CHCHD10 mutations in Italian patients with sporadic amyotrophic lateral
      sclerosis.

PMID- 25576311
TI  - Reply: Cognition in SCA21 reflects developmental and adult onset cerebellar
      cognitive affective syndrome.

PMID- 25576310
TI  - Cognition in SCA21 reflects developmental and adult onset cerebellar cognitive
      affective syndrome.

PMID- 25576312
TI  - An underexamined inequality: cultural and psychological barriers to men's
      engagement with communal roles.
AB  - Social psychological research has sought to understand and mitigate the
      psychological barriers that block women's interest, performance, and advancement
      in male-dominated, agentic roles (e.g., science, technology, engineering, and
      math). Research has not, however, correspondingly examined men's
      underrepresentation in communal roles, traditionally occupied by women (e.g.,
      careers in health care, early childhood education, and domestic roles including
      child care). In this article, we seek to provide a roadmap for research on this
      underexamined inequality by (a) outlining the benefits of increasing men's
      representation in communal roles; (b) reviewing cultural, evolutionary, and
      historical perspectives on the asymmetry in status assigned to men's and women's
      roles; and (c) articulating the role of gender stereotypes in creating social and
      psychological barriers to men's interest and inclusion in communal roles. We
      argue that promoting equal opportunities for both women and men requires a better
      understanding of the psychological barriers to men's involvement in communal
      roles. 

PMID- 25576313
TI  - Editorial.

PMID- 25576314
TI  - Patterns of cumulative abuse among female survivors of intimate partner violence:
      links to women's health and socioeconomic status.
AB  - Drawing on the Women's Health Effects Study, a community sample of women (N =
      309) who recently left an abusive partner, this study examines patterns of
      cumulative abuse experiences over the life course, their socioeconomic
      correlates, and associations with a range of health outcomes. Latent class
      analysis identified four groups of women with differing cumulative abuse
      profiles: Intimate Partner Violence (IPV) Dominant, Child Abuse and IPV, All
      Forms, and All Forms Extreme. We find a relationship pattern between cumulative
      abuse and socioeconomic circumstances, and significantly worse health outcomes
      among women with the All Forms Extreme profile. Implications for research and
      practice are discussed. 

PMID- 25576315
TI  - Improving Adherence to Evidence-Based Guidelines for Chemotherapy-Induced Nausea
      and Vomiting.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is one of the most common side
      effects experienced by patients receiving chemotherapy. Antiemetic medications
      can be used to effectively prevent and treat CINV. Choice and dose of antiemetics
      are often based on provider preference rather than evidenced-based information.
      CINV antiemetic prescribing guidelines provide an evidence-based approach and
      standardization for the management of this common side effect. The purpose of
      this quality improvement project was to improve adherence to CINV antiemetic
      guidelines. Despite distribution of CINV guidelines, there was inconsistent
      compliance with their use. When providers reported unfamiliarity with the
      guidelines, they were reintroduced and direct provider feedback was given to
      improve adherence. This quality improvement project demonstrates the need for
      continued reinforcement to sustain change that results in the best care for
      children experiencing CINV. 

PMID- 25576316
TI  - Chronic Sorrow in Mothers of Children With Cancer.
AB  - Chronic sorrow, a progressive, persistent, and endless feeling of grief, is seen
      in parents of children with chronic diseases. This study aimed to investigate
      chronic sorrow in mothers of children with cancer in selected hospitals in
      Tehran, Iran. It also sought to clarify the relationships between chronic sorrow
      and some demographic characteristics. In this descriptive, cross-sectional study,
      264 mothers attending 3 pediatric teaching hospitals in Tehran were selected
      using convenience sampling. The subjects completed a demographic questionnaire
      and Kendall Chronic Sorrow Questionnaire (Persian version). Data were analyzed
      with descriptive and inferential (Mann-Whitney and Kruskal-Wallis tests)
      statistics in SPSS 16.0. The mean score on the Kendall Chronic Sorrow
      Questionnaire was 76.39 +/- 15.81. Chronic sorrow was likely present or present
      in 97.7% of the mothers (n = 252). The mean scores on the Disparity, Sadness, and
      Getting Along subscales were 30.26 +/- 104.209, and 33.38 +/- 42.777,
      respectively, and the mean score for coping was 12.75 +/- 11.922. The
      relationships between most demographic characteristics and scores on the Kendall
      Chronic Sorrow Questionnaire were not significant. Chronic sorrow is a concept
      experienced by families of children with cancer. The health care provider's
      knowledge about this concept and its components can facilitate the development of
      better support and treatment programs and lead to improved quality of life for
      children and their families. 

PMID- 25576317
TI  - Meshing Gears: Mothers and Their Adolescents Returning to Their Social Life After
      Cancer Treatment in Taiwan.
AB  - Adolescents with cancer and their parents have to deal with the challenge of
      returning to their pre-diagnosis social life. The purpose of this study was to
      describe the subjective lived experiences of Taiwanese mothers and their
      adolescents who had completed cancer treatment and were returning to school.
      Eight Taiwanese mother-adolescent dyads were recruited by purposive sampling.
      Core themes were extracted using phenomenological method and dyadic analysis.
      Findings were metaphorically captured by the theme "meshing gears." The mothers
      and their adolescents were initially like 2 gears spinning alone, side by side
      due to experiencing different distress related to their social roles. To move
      toward a normal and healthy life journey, the mothers and their adolescents
      worked together as a well-tuned machine. This phenomenon is similar to gears
      meshing without friction to keep moving forward together. Our results suggest
      that health care professionals should provide follow-up care and
      interdisciplinary school reentry services to adolescent cancer survivors to
      improve their quality of life. 

PMID- 25576318
TI  - Pregnancy in a Patient With a Malignant Brain Tumor Taking Temozolomide: Case
      Report and Review of the Literature.
AB  - Temozolomide (TMZ), an alkylating agent used in the treatment of malignant
      gliomas, is a pregnancy category D medication that is not advised for use in
      pregnant women. We report the case of a 19-year-old woman with anaplastic
      oligodendroglioma (high-grade glioma) who became pregnant during maintenance
      chemotherapy consisting of TMZ 200 mg/m(2) administered 5 days monthly. The TMZ
      was immediately discontinued after she developed a positive pregnancy test. She
      delivered a full-term healthy baby boy with no prenatal or perinatal
      complications. Adolescents and young adults with brain tumors are often sexually
      active and should receive intensive and repeated anticipatory guidance regarding
      contraception while receiving chemotherapy. Pediatric oncology nurses are in a
      unique position to provide this education for patients and ensure that young
      women have appropriate pregnancy testing prior to chemotherapy administration. 

PMID- 25576319
TI  - "Being Mindful": Does it Help Adolescents and Young Adults Who Have Completed
      Cancer Treatment?
AB  - PURPOSE: Feelings of excitement and relief upon finishing cancer treatment are
      often juxtaposed with a time that can be challenging, distressing, and uncertain
      for adolescents and young adults (AYAs). The purpose of this study was to examine
      whether a mindful dispositional trait was associated with better adaptive
      outcomes for these young people. METHODS: AYAs who had finished cancer treatment
      (N = 76; mean age, 18.5; years, SD, 3.4 years) completed questionnaires measuring
      mindfulness, psychological distress, and uncertainty around their cancer
      experience. A median split was performed based on the total scores for the
      mindfulness measure to establish high and low mindfulness groups. RESULTS: No
      significant differences were found between these 2 groups on demographic or
      cancer variables. There were significant differences between the groups on the
      distress and uncertainty scores such that the higher mindfulness group reported
      significantly less distress and uncertainty. CONCLUSIONS: The current findings
      suggest the potential for a broader application of mindfulness to more fully
      assist young people throughout the whole pathway of cancer care.

PMID- 25576321
TI  - Which treatment option for couples with unexplained or mild male subfertility?

PMID- 25576322
TI  - Trial results raise hope for dengue fever vaccine.

PMID- 25576320
TI  - Prevention of multiple pregnancies in couples with unexplained or mild male
      subfertility: randomised controlled trial of in vitro fertilisation with single
      embryo transfer or in vitro fertilisation in modified natural cycle compared with
      intrauterine insemination with controlled ovarian hyperstimulation.
AB  - OBJECTIVES: To compare the effectiveness of in vitro fertilisation with single
      embryo transfer or in vitro fertilisation in a modified natural cycle with that
      of intrauterine insemination with controlled ovarian hyperstimulation in terms of
      a healthy child. DESIGN: Multicentre, open label, three arm, parallel group,
      randomised controlled non-inferiority trial. SETTING: 17 centres in the
      Netherlands. PARTICIPANTS: Couples seeking fertility treatment after at least 12
      months of unprotected intercourse, with the female partner aged between 18 and 38
      years, an unfavourable prognosis for natural conception, and a diagnosis of
      unexplained or mild male subfertility. INTERVENTIONS: Three cycles of in vitro
      fertilisation with single embryo transfer (plus subsequent cryocycles), six
      cycles of in vitro fertilisation in a modified natural cycle, or six cycles of
      intrauterine insemination with ovarian hyperstimulation within 12 months after
      randomisation. MAIN OUTCOME MEASURES: The primary outcome was birth of a healthy
      child resulting from a singleton pregnancy conceived within 12 months after
      randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing
      pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and
      neonatal morbidity and mortality RESULTS: 602 couples were randomly assigned
      between January 2009 and February 2012; 201 were allocated to in vitro
      fertilisation with single embryo transfer, 194 to in vitro fertilisation in a
      modified natural cycle, and 207 to intrauterine insemination with controlled
      ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples
      in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the
      in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the
      intrauterine insemination with controlled ovarian hyperstimulation group. This
      corresponds to a risk, relative to intrauterine insemination with ovarian
      hyperstimulation, of 1.10 (95% confidence interval 0.91 to 1.34) for in vitro
      fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro
      fertilisation in a modified natural cycle. These 95% confidence intervals do not
      extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy
      rates per ongoing pregnancy were 6% (7/121) after in vitro fertilisation with
      single embryo transfer, 5% (5/102) after in vitro fertilisation in a modified
      natural cycle, and 7% (8/119) after intrauterine insemination with ovarian
      hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo
      transfer compared with intrauterine insemination with ovarian hyperstimulation;
      one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared
      with intrauterine insemination with controlled ovarian hyperstimulation).
      CONCLUSIONS: In vitro fertilisation with single embryo transfer and in vitro
      fertilisation in a modified natural cycle were non-inferior to intrauterine
      insemination with controlled ovarian hyperstimulation in terms of the birth of a
      healthy child and showed comparable, low multiple pregnancy rates.Trial
      registration Current Controlled Trials ISRCTN52843371; Nederlands Trial Register
      NTR939.

PMID- 25576323
TI  - On the fate of particles liberated from hydroxyapatite coatings in vivo.
AB  - PURPOSE: Hydroxyapatite (HA) has been used as a coating for orthopaedic implants
      for over 30 years to help promote the fixation of orthopaedic implants into the
      surrounding bone. However, concerns exist about the fate of the hydroxyapatite
      coating and hydroxyapatite particles in vivo, especially in the wake of recent
      concerns about particulates from metal-on-metal bearings. METHODS: Here, we
      assess the mechanisms of particle detachment from coated orthopaedic devices as
      well as the safety and performance concerns and biomedical implications arising
      from the liberation of the particles by review of the literature. FINDINGS: The
      mechanisms that can result in the detachment of the HA coating from the implant
      can be mechanical or biochemical, or both. Mechanical mechanisms include implant
      insertion, abrasion, fatigue and micro-motion. Biochemical mechanisms that
      contribute to the liberation of HA particles include dissolution into extra
      cellular fluid, cell-mediated processes and crystallisation of amorphous phases.
      The form the particles take once liberated is influenced by a number of factors
      such as coating method, the raw powder morphology, processing parameters, coating
      thickness and coating structure. CONCLUSIONS: This review summarises and
      discusses each of these factors and concludes that HA is a safe biomimetic
      material to use as a coating and does not cause any problems in particulate form
      if liberated as debris from an orthopaedic implant.

PMID- 25576324
TI  - Neurogenetic and Neuroimaging Evidence for a Conceptual Model of Dopaminergic
      Contributions to Obesity.
AB  - As the incidence of obesity continues to rise, clinicians and researchers alike
      are seeking explanations for why some people become obese while others do not.
      While caloric intake and physical activity most certainly play a role, some
      individuals continue to gain weight despite careful attention to these factors.
      Increasing evidence suggests that genetics may play a role, with one potential
      explanation being genetic variability in genes within the neurotransmitter
      dopamine pathway. This variability can lead to a disordered experience with the
      rewarding properties of food. This review of literature examines the extant
      knowledge about the relationship between obesity and the dopaminergic reward
      pathways in the brain, with particularly strong evidence provided from
      neuroimaging and neurogenetic data. Pubmed, Google Scholar, and Cumulative Index
      to Nursing and Allied Health Literature searches were conducted with the search
      terms dopamine, obesity, weight gain, food addiction, brain regions relevant to
      the mesocortical and mesolimbic (reward) pathways, and relevant dopaminergic
      genes and receptors. These terms returned over 200 articles. Other than a few
      sentinel articles, articles were published between 1993 and 2013. These data
      suggest a conceptual model for obesity that emphasizes dopaminergic genetic
      contributions as well as more traditional risk factors for obesity, such as
      demographics (age, race, and gender), physical activity, diet, and medications. A
      greater understanding of variables contributing to weight gain and obesity is
      imperative for effective clinical treatment.

PMID- 25576325
TI  - Importin-alpha-mediated nucleolar localization of potato mop-top virus TRIPLE
      GENE BLOCK1 (TGB1) protein facilitates virus systemic movement, whereas TGB1 self
      interaction is required for cell-to-cell movement in Nicotiana benthamiana.
AB  - Recently, it has become evident that nucleolar passage of movement proteins
      occurs commonly in a number of plant RNA viruses that replicate in the cytoplasm.
      Systemic movement of Potato mop-top virus (PMTV) involves two viral transport
      forms represented by a complex of viral RNA and TRIPLE GENE BLOCK1 (TGB1)
      movement protein and by polar virions that contain the minor coat protein and
      TGB1 attached to one extremity. The integrity of polar virions ensures the
      efficient movement of RNA-CP, which encodes the virus coat protein. Here, we
      report the involvement of nuclear transport receptors belonging to the importin
      alpha family in nucleolar accumulation of the PMTV TGB1 protein and,
      subsequently, in the systemic movement of the virus. Virus-induced gene silencing
      of two importin-alpha paralogs in Nicotiana benthamiana resulted in significant
      reduction of TGB1 accumulation in the nucleus, decreasing the accumulation of the
      virus progeny in upper leaves and the loss of systemic movement of RNA-CP. PMTV
      TGB1 interacted with importin-alpha in N. benthamiana, which was detected by
      bimolecular fluorescence complementation in the nucleoplasm and nucleolus. The
      interaction was mediated by two nucleolar localization signals identified by
      bioinformatics and mutagenesis in the TGB1 amino-terminal domain. Our results
      showed that while TGB1 self-interaction is needed for cell-to-cell movement,
      importin-alpha-mediated nucleolar targeting of TGB1 is an essential step in
      establishing the efficient systemic infection of the entire plant. These results
      enabled the identification of two separate domains in TGB1: an internal domain
      required for TGB1 self-interaction and cell-to-cell movement and the amino
      terminal domain required for importin-alpha interaction in plants, nucleolar
      targeting, and long-distance movement.

PMID- 25576326
TI  - Natural compounds for solar photoprotection: a patent review.
AB  - INTRODUCTION: Ultraviolet irradiation has deleterious effects on human skin,
      including tanning, sunburn, cancer and connective tissue degradation
      (photoaging). Botanical antioxidants have been shown to be associated with
      reduced incidence of photocarcinogenesis and photoaging through their
      photoprotective profile. AREAS COVERED: Here, the authors summarized therapeutic
      patent applications concerning the employment of medicinal plants on the
      technological development of a formulation with photoprotective or photoaging
      application. So, the patent search was conducted in the databases WIPO,
      Espacenet, USPTO and Derwent, using the keywords - photoaging, photoprotection
      and the IPC A61K 8/97 (cosmetics or similar cleaning supplies obtained from
      vegetable origin, for example, plant extracts) and A61K 36/00 (medicinal
      preparations of undetermined constitution containing material from algae,
      lichens, fungi or plants, or derivatives thereof, for example, traditional herbal
      medicines). We found 180 patents, out of which 25 were evaluated using inclusion
      criteria as application of natural products with photoprotective or photoaging
      application. EXPERT OPINION: We found that some patents related to the cosmetic
      compositions for improving skin wrinkle and either preventing or reducing the
      signs of photoaging and sunburn. The cosmetic compositions are manufactured in
      the form of a lotion, gel, soluble liquid, cream, essence, oil-in-water-type or
      water-in-oil-type formulation, containing the vegetal extracts as an active
      ingredient.

PMID- 25576327
TI  - A Qualitative Case Study Exploring Nurse Engagement With Electronic Health
      Records and E-Prescribing.
AB  - There is a national focus on the adoption and use of electronic health records
      (EHRs) with electronic prescribing (e-Rx) for the goal of providing safe and
      quality care. Although there is a large body of literature on the benefits of
      adoption, there is also increasing evidence of the unintentional consequences
      resulting from use. As little is known about how use of EHR with e-Rx systems
      affects the roles and responsibilities of nurses, the purpose of this qualitative
      case study was to describe how nurses adapt to using an EHR with e-Rx system in a
      rural ambulatory care practice. Six themes emerged from the data. Findings
      revealed that nurses adjust their routine in response to providers' preferential
      behavior about EHR with e-Rx systems yet retained focus on the patient and care
      coordination. Although perceived as more efficient, EHR with e-Rx adoption
      increased workload and introduced safety risks. 

PMID- 25576329
TI  - Efficacy and tolerability of vildagliptin-based versus comparative dual therapy
      in type 2 diabetes : Results of the Austrian subpopulation of the EDGE study.
AB  - BACKGROUND: The aim of this post hoc analysis of data from the Austrian
      subpopulation of the EDGE study was the evaluation of the effectiveness and
      tolerability of vildagliptin as an add-on to an existing oral antidiabetic (OAD)
      monotherapy versus a combination therapy with two OADs without vildagliptin in
      patients with inadequately controlled type 2 diabetes. PATIENTS AND METHODS: In
      Austria, 422 patients were included. In the framework of regular visits (at
      baseline, about once per quarter, and at the study end, after 12 months), adverse
      events (AEs), courses, and changes of therapy were recorded. In addition to the
      primary end point defined in the primary study, i.e., a reduction of HbA1c by >
      0.3 % without hypoglycemia, weight gain >= 5 %, peripheral edema, or
      discontinuation due to gastrointestinal events, the most clinically relevant
      secondary end point, i.e., HbA1c reduction < 7 % without hypoglycemia or >= 3 %
      increase in body weight after 12 months was used for the analysis of the Austrian
      data. RESULTS: The initial HbA1c of all enrolled patients was 8.3 +/- 1.4 %. The
      mean reduction of HbA1c was - 1.1 % in the vildagliptin cohort and - 1.0 % in the
      comparator cohort. In the vildagliptin cohort, 56.4 % of patients, and in the
      comparator cohort, 45.9 % of patients, reached the primary end point (odds ratio:
      1.53, p = 0.04). In the vildagliptin cohort, 18.7 % of patients, and in the
      comparator cohort, 16.9 % of patients, reached the secondary end point (odds
      ratio: 1.13, p = 0.68). The incidence of hypoglycemic events (two in each
      cohort), AEs (approximately 15 % in each cohort), and serious AEs (approximately
      2 % in each cohort) was comparable between the two groups. CONCLUSION: In a "real
      life" setting, the effectiveness of vildagliptin as second-line treatment is
      superior to comparator OADs with regard to a reduction in HbA1c of greater than
      0.3 % from baseline without well-recognized side effects in patients with
      inadequately controlled type 2 diabetes (mean baseline HbA1c: 8.5 % (vildagliptin
      cohort) vs. 8.1 % (comparator cohort)).

PMID- 25576328
TI  - Identifying strains that contribute to complex diseases through the study of
      microbial inheritance.
AB  - It has been 35 y since Carl Woese reported in PNAS how sequencing ribosomal RNA
      genes could be used to distinguish the three domains of life on Earth. During the
      past decade, 16S rDNA sequencing has enabled the now frequent enumeration of
      bacterial communities that populate the bodies of humans representing different
      ages, cultural traditions, and health states. A challenge going forward is to
      quantify the contributions of community members to wellness, disease risk, and
      disease pathogenesis. Here, we explore a theoretical framework for studies of the
      inheritance of bacterial strains and discuss the advantages and disadvantages of
      various study designs for assessing the contribution of strains to complex
      diseases. 

PMID- 25576330
TI  - Is there a safer electrosurgical current for endoscopic sphincterotomy in
      patients with liver cirrhosis?
AB  - BACKGROUND: Endoscopic sphincterotomy has a higher risk of bleeding in patients
      with cirrhosis. Advanced Child stage and coagulopathy are well-known risk
      factors. We aimed to determine the role of electrosurgical currents in the
      development of endoscopic sphincterotomy bleeding in cirrhotic patients. METHODS:
      The study was a retrospective observational study and included 19,642 patients
      who underwent endoscopic retrograde cholangiopancreatography between 2004 and
      2013. The incidence of endoscopic sphincterotomy bleeding in cirrhotic patients
      who underwent sphincterotomy after 2009 with an electrosurgical generator
      applying alternating current in the pulse cut mode (Group 2) was compared with a
      historical control group who underwent endoscopic sphincterotomy between 2004 and
      2009 via blended current (Group 1). RESULTS: Group 1 included 15 patients (six
      women, nine men, mean age: 62.2 +/- 12.9 years). Group 2 included 14 patients
      (six women, eight men, mean age: 63.6 +/- 16.9 years). There was no statistically
      significant difference between the demographic and clinical characteristics of
      the two groups. Endoscopic sphincterotomy bleeding was observed in three patients
      in Group 1 (two endoscopic bleeding and one clinically significant bleeding) and
      none of the patients in Group 2 (p = 0.77). There were no cases of perforation or
      pancreatitis in both groups. One patient in Group 2 developed cholangitis.
      CONCLUSIONS: Endoscopic sphincterotomy bleeding is less frequently observed in
      patients with cirrhosis who underwent sphincterotomy with alternating mixed
      current in the pulse cut mode compared with those with blended current.

PMID- 25576331
TI  - Does neutrophil-to-lymphocyte ratio predict active ulcerative colitis?
AB  - BACKGROUND: Inflammatory markers have been studied in ulcerative colitis (UC) for
      diagnosis, disease activity, and prediction of relapse. Blood neutrophil-to
      lymphocyte (N/L) ratio has been used to determine outcomes of some malignancies
      and coronary artery disease. Blood N/L ratio is a simple sign of clinical
      inflammation. In this study, we examined N/L ratio in recurrent patients
      suffering from UC. METHODS: The aim of the present study was to analyze N/L
      ratios in serum samples of UC patients in remission and active phases. Patients'
      age, extend of the disease, disease duration, disease activity, drug, and other
      medical history were all noted for patients. C-reactive protein, erythrocyte
      sedimentation rate, and complete blood count were determined for patients.
      RESULTS: Forty-nine UC patients were admitted into the present study. The blood
      N/L ratios were significantly increased in active phase compared with inactive UC
      patients (p < 0.05). The cut-off value for N/L ratio for the detection of active
      UC patients was calculated as >= 2.3 using receiver operating characteristic
      analysis [sensitivity: 61.2 %, specificity: 66.7 %, AUC: 0.650 (0.540-0.760), p =
      0.01]. CONCLUSIONS: Present study shows that in patients with UC, the blood N/L
      ratio is associated with active disease. N/L ratio may be used as an activity
      parameter in UC.

PMID- 25576332
TI  - Peripheral facial palsy as an initial symptom of Lyme neuroborreliosis in an
      Austrian endemic area.
AB  - BACKGROUND: The objective of this study was to analyze the percentage as well as
      clinical and laboratory characteristics of Lyme neuroborreliosis (LNB) in
      patients admitted with peripheral facial palsy. Additionally, we looked for
      diagnostic criteria to distinguish Bell's palsy from facial palsy due to LNB.
      METHODS: Data collection was done retrospectively from 2007 until 2012. We
      identified 278 consecutive patients, who were admitted to the department of
      Neurology due to peripheral facial palsy. Patients were routinely investigated
      for LNB including clinical neurological examination and cerebral spinal fluid
      (CSF) analysis. Demographic and clinical data were analyzed according to a
      standardized protocol. RESULTS: In 19 (male (m) = 14/female (f) = 5) out of 278
      patients (7 %), a diagnosis of LNB was established. There were 8 patients (3 %)
      identified with varicella zoster (VZV) (m = 7/f = 1) and 13 patients (5 %) with
      facial palsy due to diabetic mononeuropathy (m = 5/f = 8). A total of 207
      patients (75 %) were diagnosed as Bell's palsy (m = 110/f = 97). Compared with
      CSF of patients with facial palsy due to VZV and diabetic mononeuropathy,
      patients with LNB showed higher cell count, protein and lactate levels, whereas
      patients with facial palsy due to diabetic mononeuropathy showed higher glucose
      level. With respect to seasonal clustering, an accumulation of 74 % of the LNB
      cases was detected from June to October, whereas in the rest of the year there
      were only 26 % of the LNB cases. Patients with Bell's palsy are more evenly
      distributed over the year. Regarding neurological signs and symptoms, radicular
      symptoms were only reported in the LNB group. Despite radicular symptoms for LNB,
      no specific signs or symptoms were found for facial palsy due to VZV, Bell's
      palsy, or diabetic mononeuropathy. CONCLUSIONS: According to the results of our
      study, we recommend CSF testing in any case for patients with facial palsy in an
      endemic area from June to October especially if additional radicular symptoms are
      present. To establish recommendations for a diagnostic workup in patients with
      facial palsy in areas endemic for Borrelia, the seasonal clustering of LNB as
      well as specific clinical features should also be confirmed in a future
      prospective trial.

PMID- 25576333
TI  - Length and weight of newborns in Croatia from 1985 to 2009.
AB  - BACKGROUND: Constitutional characteristics of humans are changing. People are
      becoming taller and they weigh more. These changes influence birth weight and
      birth length as well. METHODS: A study was conducted on 2414 mothers and their
      newborns from 1985 to 2009 in Zagreb, Croatia, to establish a secular change in
      the weight and length of infants and the factors that are most related to these
      changes. RESULTS: Birth weight has increased significantly in the past 25 years,
      and it is higher in male newborns. Taller mothers, with higher weight and body
      mass index, deliver newborns with higher birth weight. Weight gain in pregnancy
      has positive impact on birth weight. Multiparas and older and more educated women
      deliver newborns with higher weight. Birth weight does not depend on father's
      education. The number of newborns with birth weight more than 4000 g is
      increasing, but not significantly. Birth length was not significantly higher.
      Birth length is higher in male newborns, in newborns with higher birth weight and
      newborns of older and more educated mothers. CONCLUSION: Better life conditions
      and better health care improves population constitutional characteristics that
      have implications in higher birth weight and birth length. This could be an
      important change that influences delivery modalities.

PMID- 25576334
TI  - Excessive sweating induced by interaction between agomelatine and duloxetine
      hydrochloride: case report and review of the literature.
AB  - OBJECTIVE: In this case report, we describe a case in which the clinical pharmacy
      team was asked to provide recommendations on possible continued use of
      combination antidepressants in a 62-year-old Slovenian female patient with major
      depressive disorder following agomelatine and duloxetine hydrochloride-induced
      excessive sweating. When agomelatine was administered as an additional treatment,
      drug-induced excessive sweating was observed after a daily intake of 90 mg of
      duloxetine hydrochloride and 25 mg of agomelatine. After thorough discussion, it
      was decided not to rechallenge with agomelatine because of the serious adverse
      effect. After agomelatine discontinuation and switching to trazodone, symptoms
      immediately improved. DISCUSSION: Duloxetine hydrochloride-induced sweating has
      been reported frequently, but excessive sweating induced by agomelatine and
      duloxetine hydrochloride has not been reported in the literature. The adverse
      effect was determined by a clinical pharmacist using the Naranjo probability
      scale and was probably associated with agomelatine use (6 points) and possibly
      associated with duloxetine hydrochloride use (4 points). The exact mechanism for
      this adverse effect in this patient is not known, but we believe that a
      pharmacodynamic drug-drug interaction between agomelatine and duloxetine
      hydrochloride had occurred. CONCLUSION: Such a case has not yet been described in
      literature; however, an adverse effect associated with drug-drug interaction can
      occur, as this report clearly demonstrates. The benefits of this antidepressant
      combination need to be carefully balanced with the risks associated with its use.
      This case report also highlights the increased potential for adverse reactions
      when prescribing antidepressant combinations and importance of clinical
      pharmacists' involvement in the psychiatric patients' pharmacotherapy.

PMID- 25576335
TI  - Does corticosteroid treatment cause prolonged recovery and increased total
      bilirubin level in severe ADAMTS-13-deficient TTP patient?
AB  - A 41-year-old female patient complaining of fatigue, headache, mild confusion,
      and rush on her lower extremities was admitted to our emergency department.
      Laboratory tests revealed that he had anemia, thrombocytopenia, and increased
      levels of indirect bilirubin and lactic dehydrogenase (LDH) in blood tests.
      Direct and indirect Coombs tests were negative, and fragmented erythrocytes were
      observed in peripheral blood smears. The patient was diagnosed with thrombotic
      thrombocytopenic purpura (TTP). The best supportive care was provided.
      Therapeutic plasma exchange (TPE) and 1 mg/kg methylprednisolone treatments were
      administered. On the 10th day of treatment, LDH level and fragmented red blood
      cells in peripheral blood smear were decreased, but his direct and indirect
      bilirubin levels increased despite the fact that he was treated with 1 mg/kg
      methylprednisolone and TPE. The patient had severe ADAMTS-13 deficiency. After
      discontinued steroids treatment, his bilirubin level normalized within 4 days. On
      the 4th day after bilirubin level normalized, vincristine treatment was
      administered. TPE was also continued. There was no consensus about the optimal
      schedule for discontinuing plasmapheresis therapy, and also we observed total
      bilirubin level improvement with discontinued corticosteroid treatment. In this
      case, corticosteroid treatment was linked with the increase of total bilirubin
      level in severe ADAMTS-13-deficient TTP patient.

PMID- 25576337
TI  - Functional Tuning of CARs Reveals Signaling Threshold above Which CD8+ CTL
      Antitumor Potency Is Attenuated due to Cell Fas-FasL-Dependent AICD.
AB  - Chimeric antigen receptor (CAR) development is biased toward selecting constructs
      that elicit the highest magnitude of T-cell functional outputs. Here, we show
      that components of CAR extracellular spacer and cytoplasmic signaling domain
      modulate, in a cooperative manner, the magnitude of CD8(+)CTL activation for
      tumor-cell cytolysis and cytokine secretion. Unexpectedly, CAR constructs that
      generate the highest in vitro activity, either by extracellular spacer length
      tuning or by the addition of cytoplasmic signaling modules, exhibit attenuated
      antitumor potency in vivo, whereas CARs tuned for moderate signaling outputs
      mediate tumor eradication. Recursive CAR triggering renders CTLs expressing
      hyperactive CARs highly susceptible to activation-induced cell death (AICD) as a
      result of augmented FasL expression. CAR tuning using combinations of
      extracellular spacers and cytoplasmic signaling modules, which limit AICD of
      CD8(+)CTLs, may be a critical parameter for achieving clinical activity against
      solid tumors.

PMID- 25576336
TI  - Peptide/MHC tetramer-based sorting of CD8+ T cells to a leukemia antigen yields
      clonotypes drawn nonspecifically from an underlying restricted repertoire.
AB  - Testing of T cell-based cancer therapeutics often involves measuring cancer
      antigen-specific T-cell populations with the assumption that they arise from in
      vivo clonal expansion. This analysis, using peptide/MHC tetramers, is often
      ambiguous. From a leukemia cell line, we identified a CDK4-derived peptide
      epitope, UNC-CDK4-1 (ALTPVVVTL), that bound HLA-A*02:01 with high affinity and
      could induce CD8+ T-cell responses in vitro. We identified UNC-CDK4-1/HLA-A*02:01
      tetramer+ populations in 3 of 6 patients with acute myeloid leukemia who had
      undergone allogeneic stem cell transplantation. Using tetramer-based, single-cell
      sorting and T-cell receptor beta (TCRbeta) sequencing, we identified recurrent
      UNC-CDK4-1 tetramer-associated TCRbeta clonotypes in a patient with a UNC-CDK4-1
      tetramer+ population, suggesting in vivo T-cell expansion to UNC-CDK4-1. In
      parallel, we measured the patient's TCRbeta repertoire and found it to be highly
      restricted/oligoclonal. The UNC-CDK4-1 tetramer-associated TCRbeta clonotypes
      represented >17% of the entire TCRbeta repertoire-far in excess of the UNC-CDK4-1
      tetramer+ frequency-indicating that the recurrent TCRbeta clonotypes identified
      from UNC-CDK-4-1 tetramer+ cells were likely a consequence of the extremely
      constrained T-cell repertoire in the patient and not in vivo UNC-CDK4-1-driven
      clonal T-cell expansion. Mapping recurrent TCRbeta clonotype sequences onto
      TCRbeta repertoires can help confirm or refute antigen-specific T-cell expansion
      in vivo.

PMID- 25576338
TI  - Participation in four rounds of a French colorectal cancer screening programme
      with guaiac faecal occult blood test: a population-based open cohort study.
AB  - OBJECTIVES: Four randomized controlled trials have demonstrated the efficacy of
      screening using a guaiac faecal occult blood test (gFOBT) on colorectal cancer
      (CRC) mortality. Whether their results are transposable to the real world is
      unknown. This study aimed to assess the determinants of participation in the
      first four rounds of the CRC screening programme using a gFOBT implemented since
      2003 in the Haut-Rhin (Alsace) part of the French national programme. METHODS: We
      performed a population-based open cohort study of all residents aged 50-74,
      around 200,000 people. They were invited by mail to participate every other year.
      The gFOBT kits (Hemoccult II) were first provided by general practitioners, and
      then directly mailed to persons who failed to comply. RESULTS: The uptake
      decreased significantly across all rounds, from 54.3% to 47.1% (p < 0.0001),
      mainly in people younger than 60. The proportion of people screened by general
      practitioners increased significantly from 77.0% in the first round to 84.2% in
      the fourth (p < 0.01). Overall, 61.3% of the invited population participated at
      least once, and 14.3% had completed all the four tests. The colonoscopy uptake
      was around 91%, among the highest ever reported. CONCLUSIONS: Despite the
      involvement of general practitioners, the uptake and adherence to repeat testing
      are modest and deteriorate with time, so that the reduction in CRC mortality in
      reality will be significantly lower than that in the trials. The benefit-risk
      balance of the French programme is, at present, less favourable than that shown
      in the trials.

PMID- 25576339
TI  - Measuring the burden of interval cancers in long-standing screening mammography
      programmes.
AB  - OBJECTIVES: Mammography screening programme sensitivity is evaluated by comparing
      the interval cancer rate (ICR) with the expected breast cancer incidence without
      screening, ie. the proportional interval cancer rate (PICR). The PICR is usually
      found by extrapolating pre-screening incidence rates, whereas ICR is calculated
      from data available in the screening programmes. As there is no consensus
      regarding estimation of background incidence, we seek to validate the ICR measure
      against the PICR. METHODS: Screening data from the three mammography screening
      programmes of Stockholm, Copenhagen, and Funen in the period 1989-2011 provided
      data to calculate the ICR. The most commonly described methods of extrapolating
      pre-screening incidence rates to calculate the PICR were illustrated and PICRs
      were calculated by year and programme using these different methods and compared
      with the ICRs. RESULTS: PICRs varied greatly, reaching a difference of 32-34% in
      Stockholm, 79% in Copenhagen, and 100-106% in Funen between the highest and the
      lowest value, depending on which method was applied. PICRs exhibited large
      variations yearly and from programme to programme. ICRs did not vary to the same
      extent, ranging on average from 0.100 to 0.136 in the first 12-months and between
      0.201 and 0.225 in the last 12-months of the two-year period after a negative
      screen across the three programmes. CONCLUSION: The value of the PICR is hugely
      influenced by which method is applied, whereas the ICR is calculated purely on
      data available within programmes. We find that the PICR, the establishing
      indicator for sensitivity, could preferably be replaced by the ICR.

PMID- 25576341
TI  - microRNA-143 is associated with the survival of ALDH1+CD133+ osteosarcoma cells
      and the chemoresistance of osteosarcoma.
AB  - This study investigated the role of miR-143 in the chemoresistance of
      osteosarcoma tumor cells and the associated mechanisms. Real-time PCR was used to
      measure miR-143 levels. Western blot was used to detect protein expression. Cell
      proliferation was analyzed by MTT assay and Matrigel colony formation assay.
      Forced miR-143 expression was established by adenoviral vector infection. Cell
      death was detected by Hoechst33342 staining. Loss of miR-143 expression was
      observed in osteosarcomas, which correlated with shorter survival of patients
      with osteosarcomas underlying chemotherapy. In chemoresistant SAOS-2 and U2OS
      osteosarcomas cells, miR-143 levels were significantly downregulated and
      accompanied by increases in ATG2B, Bcl-2, and/or LC3-II protein levels, high rate
      of ALDH1(+)CD133(+) cells, and an increase in Matrigel colony formation ability.
      H2O2 upregulated p53 and miR-143, but downregulated ATG2B, Bcl-2, and LC3-I
      expression in U2OS cells (wild-type p53) but not in SAOS-2 (p53-null) cells.
      Forced miR-143 expression significantly reversed chemoresistance as well as
      downregulation of ATG2B, LC3-I, and Bcl-2 expression in SAOS-2- and U2OS
      resistant cells. Forced miR-143 expression significantly inhibited tumor growth
      in xenograft SAOS-2-Dox and U2OS-Dox animal models. Loss of miR-143 expression is
      associated with poor prognosis of patients with osteosarcoma underlying
      chemotherapy. The chemoresistance of osteosarcoma tumor cells to doxorubicin is
      associated with the downregulation of miR-143 expression, activation of
      ALDH1(+)CD133(+) cells, activation of autophagy, and inhibition of cell death.
      miR-143 may play a crucial role in the chemoresistance of osterosarcoma tumors. 

PMID- 25576340
TI  - Direct intracardiac injection of umbilical cord-derived stromal cells and
      umbilical cord blood-derived endothelial cells for the treatment of ischemic
      cardiomyopathy.
AB  - The development of new therapeutic strategies is necessary to reduce the
      worldwide social and economic impact of cardiovascular disease, which produces
      high rates of morbidity and mortality. A therapeutic option that has emerged in
      the last decade is cell therapy. The aim of this study was to compare the effect
      of transplanting human umbilical cord-derived stromal cells (UCSCs), human
      umbilical cord blood-derived endothelial cells (UCBECs) or a combination of these
      two cell types for the treatment of ischemic cardiomyopathy (IC) in a Wistar rat
      model. IC was induced by left coronary artery ligation, and baseline
      echocardiography was performed seven days later. Animals with a left ventricular
      ejection fraction (LVEF) of <=40% were selected for the study. On the ninth day
      after IC was induced, the animals were randomized into the following experimental
      groups: UCSCs, UCBECs, UCSCs plus UCBECs, or vehicle (control). Thirty days after
      treatment, an echocardiographic analysis was performed, followed by euthanasia.
      The animals in all of the cell therapy groups, regardless of the cell type
      transplanted, had less collagen deposition in their heart tissue and demonstrated
      a significant improvement in myocardial function after IC. Furthermore, there was
      a trend of increasing numbers of blood vessels in the infarcted area. The median
      value of LVEF increased by 7.19% to 11.77%, whereas the control group decreased
      by 0.24%. These results suggest that UCSCs and UCBECs are promising cells for
      cellular cardiomyoplasty and can be an effective therapy for improving cardiac
      function following IC. 

PMID- 25576342
TI  - Inhibition of glycogen synthase kinase-3beta prevents sympathetic
      hyperinnervation in infarcted rats.
AB  - We have demonstrated that nerve growth factor (NGF) expression in the myocardium
      is selectively increased during chronic stage of myocardial infarction, resulting
      in sympathetic hyperinnervation. Glycogen synthase kinase-3 (GSK-3) signal has
      been shown to play key roles in the regulation of cytoskeletal assembly during
      axon regeneration. We assessed whether lithium, a GSK-3 inhibitor, attenuates
      cardiac sympathetic reinnervation after myocardial infarction through attenuated
      NGF expression and Tau expression. Twenty-four hours after ligation of the
      anterior descending artery, male Wistar rats were randomized to either LiCl or
      SB216763, chemically unrelated inhibitors of GSK-3beta, a combination of LiCl and
      SB216763, or vehicle for four weeks. Myocardial norepinephrine levels revealed a
      significant elevation in vehicle-treated rats compared with sham-operated rats,
      consistent with excessive sympathetic reinnervation after infarction.
      Immunohistochemical analysis for sympathetic nerve also confirmed the change of
      myocardial norepinephrine. This was paralleled by a significant upregulation of
      NGF protein and mRNA in the vehicle-treated rats, which was reduced after
      administering either LiCl, SB216763, or combination. Arrhythmic scores during
      programmed stimulation in the vehicle-treated rats were significantly higher than
      those treated with GSK-3 inhibitors. Addition of SB216763 did not have additional
      beneficial effects compared with those seen in rats treated with LiCl alone.
      Furthermore, lithium treatment increased Tau1 and decreased AT8 and AT180 levels.
      Chronic use of lithium after infarction, resulting in attenuated sympathetic
      reinnervation by GSK-3 inhibition, may modify the arrhythmogenic response to
      programmed electrical stimulation. 

PMID- 25576344
TI  - Greater maternal insensitivity in childhood predicts greater electrodermal
      reactivity during conflict discussions with romantic partners in adulthood.
AB  - In this study, we drew on prospective, longitudinal data to investigate the long
      term predictive significance of the quality of early parent-child relationship
      experiences for adults' sympathetic nervous system (SNS) activity during conflict
      discussions with their romantic partners. Maternal sensitivity was repeatedly
      assessed across childhood via direct observations of mother-child interactions.
      When the children in the study became adults (34-37 years old), electrodermal
      activity-an index of SNS arousal and a psychophysiological marker of behavioral
      inhibition-was recorded for 37 participants while at rest and while they
      attempted to resolve conflicts in their romantic relationships. Individuals who
      had experienced less sensitive maternal caregiving during childhood had greater
      increases in electrodermal activity during conflict discussions with their adult
      partners, relative to resting conditions. This longitudinal association was not
      accounted for by observed or self-reported romantic-relationship quality, gender,
      ethnicity, or early socioeconomic factors. 

PMID- 25576343
TI  - Extracellular regulated protein kinases 1/2 phosphorylation is required for
      hepatic differentiation of human umbilical cord-derived mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) have the capacity to restore liver function by
      differentiating into hepatocyte like cells. However, the underlying mechanisms
      are not well understood. Here, we have investigated the signals involved in the
      hepatic differentiation of human umbilical cord-derived mesenchymal stem cells
      (hUCMSCs). hUCMSCs were treated with mouse fetal liver-conditioned medium (FLCM)
      to induce hepatic differentiation. Flow cytometry, reverse transcription PCR,
      real-time PCR, immunocytochemistry, and polymerase chain reaction (PCR) array
      were used to detect the expression of MSC- and hepotocyte-specific markers in
      FLCM-treated hUCMSCs. Urea production and cytochrome P450 3A4 (CYP3A4) activity
      were used as indicators to evaluate liver cell characteristics. Raf/mitogen
      activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)
      was analyzed in hUCMSCs by Western blotting. Following FLCM treatment, expression
      of MSC-specific markers decreased, while hepatocyte-specific gene expression was
      increased. Urea production, albumin secretion, glycogen storage, and CYP3A4
      activity were significantly enhanced in FLCM-treated cells. In addition, ERK1/2
      phosphorylation was increased in a time-dependent manner through Raf/MEK/ERK
      pathway, and phosphorylation was sustained at a high level during hepatic
      induction. Inhibition of ERK1/2 activation by U0126 (an ERK1/2 inhibitor) and
      pFLAG-CMV-ERK1(K71R) (negative mutant of ERK1) reversed the expression of liver
      specific genes in hUCMSCs and affected hepatic function significantly. In
      summary, this work shows that ERK1/2 phosphorylation plays an important role in
      inducing hepatic differentiation of hUCMSCs in FLCM. 

PMID- 25576346
TI  - Explicit memory and implicit memory in occipital lobe stroke patients.
AB  - BACKGROUND: Occipital stroke patients mainly showed cortical blindness and
      unilateral vision loss; memory is generally reserved. Recent reports from
      neuroimaging show the occipital lobe may be involved in the processing of
      implicit memory (IM), especially the perception type of IM processing. In this
      study, we explored the explicit memory (EM) and IM damage in occipital lobe
      stroke patients. METHODS: A total of 25 occipital strokes and 29 years of age,
      educational level equivalent healthy controls (HCs), evaluated by using immediate
      recall, delayed recall, recognition for EM tasks, picture identification, and
      category exemplar generation for IM tasks. RESULTS: There was no significant
      difference between occipital stroke patients and HCs in EM tasks and category
      exemplar generation task. In the picture identification task, occipital lobe
      stroke group score was poorer than HC group, the results were statistically
      significant, but in the pictures identify rate, occipital stroke patients and
      normal control group had no significant difference. CONCLUSIONS: The occipital
      stroke patients may have IM damage, primarily damage the perception type of IM
      priming effects, which was unrelated with their cortical blindness.

PMID- 25576345
TI  - Longitudinal progress of overall intelligibility, voice, resonance, articulation
      and oromyofunctional behavior during the first 21 months after Belgian facial
      transplantation.
AB  - PURPOSE: The purpose of this study is to document the longitudinal progress of
      speech intelligibility, speech acceptability, voice, resonance, articulation and
      oromyofunctional behavior in a male facial transplant patient 8 days, 15 days, 5
      months, 12 months and, finally, 21 months after surgery. METHOD: Identical
      objective (Dysphonia Severity Index, nasometry, acoustic analysis) and subjective
      (consensus perceptual evaluation, Dutch speech intelligibility test; flexible
      videolaryngostroboscopy/naso-endoscopy) assessment techniques and questionnaires
      (speech and voice handicap index, oral health impact profile, facial disability
      index) were used during each of the five postsurgical assessments. RESULTS: The
      pattern of results shows a longitudinal progress of speech intelligibility and
      acceptability and of the interactive processes underpinning overall speech
      intelligibility. Vocal quality is normal and resonance is characterized by
      hypernasality. The phonetic inventory is complete but four phonetic disorders
      remain. Outcomes pertaining to articulation (formant analysis) show evident
      progress over time. Lip functions are improving but still decreased. CONCLUSIONS:
      Transplantation of the face in this patient has largely restored speech. To what
      extent resonance, articulation, and lip functions can be enhanced by the
      permanent use of a palatal obturator, by specialized facial and lip movement
      exercises in combination with motor-oriented speech therapy, is subject for
      further research. Learning outcomes Facial transplantation: Readers will be able
      to (1) describe the relationship between facial transplantation and the impact on
      speech and oromyofunctional behavior, (2) identify variables that influence the
      outcome after facial transplantation, (3) define an assessment protocol after
      facial transplantation, (4) define facial transplantation.

PMID- 25576347
TI  - Predicting stroke outcome using clinical- versus imaging-based scoring system.
AB  - BACKGROUND: Several models to predict outcome in ischemic stroke patients
      receiving intravenous (i.v.) alteplase can be divided into clinical-based and
      imaging-based systems. Alberta Stroke Program Early Computed Tomography (CT)
      Score (ASPECTS) and Dense cerebral artery sign/early infarct signs on admission
      CT scan, prestroke modified Rankin Scale (mRS) score, Age, Glucose level at
      baseline, Onset-to-treatment time, and baseline National Institutes of Health
      Stroke Scale score (DRAGON) are typical imaging- and clinical-based scoring
      systems, respectively. Therefore, we compared predictability of stroke outcome of
      clinical (DRAGON)- and imaging (ASPECTS)-based scoring systems. METHODS: We
      analyzed patients who were diagnosed with middle cerebral artery territory stroke
      and treated with i.v. alteplase at Gachon University Gil Hospital over 5 years
      and compared performance of 2 scoring systems for prediction of good functional
      outcome (mRS, 0-2) with Pearson correlation and area under the curve-receiver
      operating characteristic (AUC-ROC). In addition, we analyzed predicting power of
      several clinical factors and 2 scoring systems by multiple regression analysis.
      RESULTS: Study population (N = 120) had mean age of 66.2 +/- 13.2 years. ASPECTS
      (r = -.841, P < .0001) and DRAGON (r = .657, P < .0001) were significantly
      correlated with good functional outcome. In addition, statistical comparisons
      suggested that ASPECTS (AUC-ROC, .972; 95% confidence interval [CI], .947-.996)
      is significantly superior to DRAGON (AUC-ROC, .854; 95% CI, .786-.922) in
      predicting functional outcome (difference between areas, .118 +/- .0332; 95% CI,
      .0559-.180, P = .0002). Multiple regression analysis revealed that ASPECTS was
      the independent predictor of good prognosis (OR, 6.59 per 1-point increase; 95%
      CI, 2.35-18.49; P < .0001 and OR, 77.67 for ASPECTS >= 8; 95% CI, 14.30-421.79; P
      < .0001). CONCLUSIONS: ASPECTS is superior method for predicting functional
      outcome in acute ischemic stroke patients receiving i.v. alteplase compared with
      DRAGON and integration of ASPECTS score into clinical care pathway as decision
      making tool can be reasonable.

PMID- 25576348
TI  - Determinants of white matter hyperintensity burden differ at the extremes of ages
      of ischemic stroke onset.
AB  - BACKGROUND: Age is a well-known risk factor for both stroke and increased burden
      of white matter hyperintensity (WMH), as detected on magnetic resonance imaging
      (MRI) scans. However, in patients diagnosed with ischemic stroke (IS), WMH volume
      (WMHv) varies significantly across age groups. We sought to examine the
      determinants of WMH burden across the ages of stroke onset with the goal to
      uncover potential age-specific stroke prevention targets. METHODS: Adult subjects
      from an ongoing hospital-based cohort study of IS patients with admission brain
      MRI were categorized as having early (<55 years), late (>75 years), or average
      (55-75 years) age of stroke onset. WMHv was measured using a previously
      validated, MRI-based semi-automated method and normalized for linear regression
      analyses. RESULTS: Of 1008 IS subjects, 249 had early-onset stroke (24.7%), and
      311 had late-onset stroke (30.9%). In multivariable analysis of WMHv using
      backward stepwise selection, only age (beta = .02, P = .018), hypertension (beta
      = .24, P = .049), and history of tobacco use (beta = .38, P = .001) were
      independently associated with WMHv in patients with early-onset stroke, whereas
      male sex (beta = -.30, P = .007), hyperlipidemia (beta = -.27, P = .015), and
      current alcohol use (beta = .23, P = .034) were independently associated with
      WMHv in patients with late-onset stroke. CONCLUSIONS: History of tobacco use is a
      strong independent predictor of WMH burden in patients with early-onset stroke,
      whereas age is no longer associated with WMHv in IS patients older than 75 years
      of age. These findings suggest that the major risk factors to target for stroke
      prevention differ across age groups and may be modifiable.

PMID- 25576349
TI  - Sporadic Carney complex without PRKAR1A mutation in a young patient with ischemic
      stroke.
AB  - We describe a 29-year-old male, with a previous history of testicular tumor, who
      presented with a posterior circulation ischemic stroke associated to an atrial
      myxoma. Dermatologic observation disclosed spotty skin and mucosal pigmentation
      (lentigines), and a cutaneous myxoma was histopathologically confirmed. Although
      there was no family history of any of the Carney complex (CNC) features and no
      mutations in the PRKAR1A gene were found, these findings lead to the diagnosis of
      CNC. We emphasize the importance of recognizing this entity in young patients
      with stroke. 

PMID- 25576350
TI  - Determinants of the health-related quality of life for stroke survivors.
AB  - BACKGROUND: To identify the factors that greatly influence stroke-specific health
      related quality of life (HRQoL). The following 5 categories were explored
      simultaneously in a cross-sectional study: (1) sociodemographic, (2) clinical,
      (3) symptom severity and physical, (4) neurocognitive, and (5) psychosocial
      factors. METHODS: A total of 134 patients who experienced a stroke at least 6
      months prior were recruited by convenience sampling. Subjective HRQoL levels were
      measured using disease-specific scales, the Stroke-specific Quality of Life (SS
      QoL)-12, and the modified SS-QoL-8, with a newly added subscale, "activities," as
      well as the total score. After sociodemographic and clinical data were collected,
      patients were scored with the National Institutes of Health Stroke Scale, Mini
      Mental State Examination, and the Barthel Index (BI). All patients completed the
      SS-QoL-12, SS-QoL-8, and Stroke Impact Scale (SIS) version 3.0 by self-report.
      Multiple hierarchical regressions were conducted using the stepwise method.
      RESULTS: Compared with neurocognitive (type 4) factors, the stroke-specific HRQoL
      levels were significantly impacted by psychosocial (type 5) and "symptom severity
      and physical" (type 3) factors. The individual factors that significantly
      influenced stroke-specific HRQoL were the SIS 3.0 social participation subscore
      and the BI total score. None of the neurocognitive (type 4) factors were
      significantly associated with the either SS-QoL-12 score or SS-QoL-8 score.
      CONCLUSIONS: Research and health care aimed to facilitate social participation
      and limitations in performing daily activities can be beneficial to improve the
      HRQoL levels of the patients with stroke.

PMID- 25576352
TI  - A novel neural-inspired learning algorithm with application to clinical risk
      prediction.
AB  - Clinical risk prediction - the estimation of the likelihood an individual is at
      risk of a disease - is a coveted and exigent clinical task, and a cornerstone to
      the recommendation of life saving management strategies. This is especially
      important for individuals at risk of cardiovascular disease (CVD) given the fact
      that it is the leading causes of death in many developed counties. To this end,
      we introduce a novel learning algorithm - a key factor that influences the
      performance of machine learning-based prediction models - and utilities it to
      develop CVD risk prediction tool. This novel neural-inspired algorithm, called
      the Artificial Neural Cell System for classification (ANCSc), is inspired by
      mechanisms that develop the brain and empowering it with capabilities such as
      information processing/storage and recall, decision making and initiating actions
      on external environment. Specifically, we exploit on 3 natural neural mechanisms
      responsible for developing and enriching the brain - namely neurogenesis,
      neuroplasticity via nurturing and apoptosis - when implementing ANCSc algorithm.
      Benchmark testing was conducted using the Honolulu Heart Program (HHP) dataset
      and results are juxtaposed with 2 other algorithms - i.e. Support Vector Machine
      (SVM) and Evolutionary Data-Conscious Artificial Immune Recognition System (EDC
      AIRS). Empirical experiments indicate that ANCSc algorithm (statistically)
      outperforms both SVM and EDC-AIRS algorithms. Key clinical markers identified by
      ANCSc algorithm include risk factors related to diet/lifestyle, pulmonary
      function, personal/family/medical history, blood data, blood pressure, and
      electrocardiography. These clinical markers, in general, are also found to be
      clinically significant - providing a promising avenue for identifying potential
      cardiovascular risk factors to be evaluated in clinical trials. 

PMID- 25576353
TI  - Clinical outcomes in elderly patients with advanced non-small cell lung cancer:
      results from ARIES, a bevacizumab observational cohort study.
AB  - AIMS: Retrospective analyses from first-line clinical studies in advanced non
      small cell lung cancer (NSCLC) have reported conflicting results on progression
      free survival (PFS) and overall survival benefits with the addition of
      bevacizumab to chemotherapy in elderly patients. Here we report effectiveness and
      safety outcomes by age subgroup for patients with NSCLC in the ARIES
      observational cohort study. MATERIALS AND METHODS: ARIES enrolled patients with
      advanced non-squamous NSCLC who received first-line bevacizumab-containing
      treatment per physician's choice. Kaplan-Meier estimates were used to calculate
      medians and 95% confidence intervals for PFS and overall survival for patients
      aged <65, >=65, <75 and >=75 years. RESULTS: In total, 1967 patients receiving
      first-line treatment with bevacizumab and chemotherapy were enrolled. The median
      PFS and overall survival values were 6.4 (95% confidence interval = 6.0-6.8) and
      14.2 (95% confidence interval = 12.7-15.2) months for patients aged <65 years,
      respectively, and 6.8 (95% confidence interval = 6.3-7.0) and 12.1 (95%
      confidence interval = 11.4-13.1) months for patients >=65 years, respectively.
      For patients <75 years, the median PFS and overall survival values were 6.6 (95%
      confidence interval = 6.3-6.9) and 13.5 (95% confidence interval = 12.6-14.5)
      months, respectively, and 6.6 (95% confidence interval = 5.9-7.1) and 11.6 (95%
      confidence interval = 10.0-12.5) months, respectively, for patients >=75 years.
      Incidence proportions of bevacizumab-associated adverse events were generally
      similar across all age groups. CONCLUSIONS: Data from the ARIES study suggest
      that treatment with bevacizumab in combination with chemotherapy is a viable
      first-line treatment option for elderly bevacizumab-eligible patients with
      advanced non-squamous NSCLC.

PMID- 25576354
TI  - The generation of centripetal force when walking in a circle: insight from the
      distribution of ground reaction forces recorded by plantar insoles.
AB  - BACKGROUND: Turning involves complex reorientation of the body and is accompanied
      by asymmetric motion of the lower limbs. We investigated the distribution of the
      forces under the two feet, and its relation to the trajectory features and body
      medio-lateral displacement during curved walking. METHODS: Twenty-six healthy
      young participants walked under three different randomized conditions: in a
      straight line (LIN), in a circular clockwise path and in a circular counter
      clockwise path. Both feet were instrumented with Pedar-X insoles. An
      accelerometer was fixed to the trunk to measure the medio-lateral inclination of
      the body. We analyzed walking speed, stance duration as a percent of gait cycle
      (%GC), the vertical component of the ground reaction force (vGRF) of both feet
      during the entire stance, and trunk inclination. RESULTS: Gait speed was faster
      during LIN than curved walking, but not affected by the direction of the curved
      trajectory. Trunk inclination was negligible during LIN, while the trunk was
      inclined toward the center of the path during curved trajectories. Stance
      duration of LIN foot and foot inside the curved trajectory (Foot-In) was longer
      than for foot outside the trajectory (Foot-Out). vGRF at heel strike was larger
      in LIN than in curved walking. At mid-stance, vGRF for both Foot-In and Foot-Out
      was higher than for LIN foot. At toe off, vGRF for both Foot-In and Foot-Out was
      lower than for LIN foot; in addition, Foot-In had lower vGRF than Foot-Out.
      During curved walking, a greater loading of the lateral heel occurred for Foot
      Out than Foot-In and LIN foot. On the contrary, a smaller lateral loading of the
      heel was found for Foot-In than LIN foot. At the metatarsal heads, an opposite
      behaviour was seen, since lateral loading decreased for Foot-Out and increased
      for Foot-In. CONCLUSIONS: The lower gait speed during curved walking is shaped by
      the control of trunk inclination and the production of asymmetric loading of heel
      and metatarsal heads, hence by the different contribution of the feet in
      producing the body inclination towards the centre of the trajectory.

PMID- 25576355
TI  - A co-expression gene network associated with developmental regulation of apple
      fruit acidity.
AB  - Apple fruit acidity, which affects the fruit's overall taste and flavor to a
      large extent, is primarily determined by the concentration of malic acid.
      Previous studies demonstrated that the major QTL malic acid (Ma) on chromosome 16
      is largely responsible for fruit acidity variations in apple. Recent advances
      suggested that a natural mutation that gives rise to a premature stop codon in
      one of the two aluminum-activated malate transporter (ALMT)-like genes (called
      Ma1) is the genetic causal element underlying Ma. However, the natural mutation
      does not explain the developmental changes of fruit malate levels in a given
      genotype. Using RNA-seq data from the fruit of 'Golden Delicious' taken at 14
      developmental stages from 1 week after full-bloom (WAF01) to harvest (WAF20), we
      characterized their transcriptomes in groups of high (12.2 +/- 1.6 mg/g fw, WAF03
      WAF08), mid (7.4 +/- 0.5 mg/g fw, WAF01-WAF02 and WAF10-WAF14) and low (5.4 +/-
      0.4 mg/g fw, WAF16-WAF20) malate concentrations. Detailed analyses showed that a
      set of 3,066 genes (including Ma1) were expressed not only differentially (P FDR
      < 0.05) between the high and low malate groups (or between the early and late
      developmental stages) but also in significant (P < 0.05) correlation with malate
      concentrations. The 3,066 genes fell in 648 MapMan (sub-) bins or functional
      classes, and 19 of them were significantly (P FDR < 0.05) co-enriched or co
      suppressed in a malate dependent manner. Network inferring using the 363 genes
      encompassed in the 19 (sub-) bins, identified a major co-expression network of
      239 genes. Since the 239 genes were also differentially expressed between the
      early (WAF03-WAF08) and late (WAF16-WAF20) developmental stages, the major
      network was considered to be associated with developmental regulation of apple
      fruit acidity in 'Golden Delicious'.

PMID- 25576356
TI  - Inhibition of HIV-1 entry by the tricyclic coumarin GUT-70 through the
      modification of membrane fluidity.
AB  - Membrane fusion between host cells and HIV-1 is the initial step in HIV-1
      infection, and plasma membrane fluidity strongly influences infectivity. In the
      present study, we demonstrated that GUT-70, a natural product derived from
      Calophyllum brasiliense, stabilized plasma membrane fluidity, inhibited HIV-1
      entry, and down-regulated the expression of CD4, CCR5, and CXCR4. Since GUT-70
      also had an inhibitory effect on viral replication through the inhibition of NF
      kappaB, it is expected to be used as a dual functional and viral mutation
      resistant reagent. Thus, these unique properties of GUT-70 enable the development
      of novel therapeutic agents against HIV-1 infection. 

PMID- 25576357
TI  - DNA damage and ER stress contribute to oblongifolin C-induced cell killing in
      Bax/Bak-deficient cells.
AB  - A key clinical problem in oncology is the treatment of apoptosis-resistant
      tumors. Tumor cells deficient in both of the proapoptotic proteins Bax and Bak
      are protected against most chemotherapeutic drug-induced apoptosis. We report
      here that a natural compound, oblongifolin C (OC), effectively eliminates Bax/Bak
      deficient murine embryonic fibroblasts and colon carcinoma HCT116 cells. OC not
      only triggers DNA double-strand breaks and DNA damage response, but also inhibits
      repair of DNA damage. In addition, OC induces ER stress through upregulation of
      the transcription factor CHOP and activation of JNK kinases. Upon treatment with
      OC, cells undergo Bax/Bak-independent, caspase-mediated apoptosis. Taken
      together, our data establish a rationale for the broad use of OC to treat
      apoptosis deficient tumors. 

PMID- 25576358
TI  - EpCAM is up-regulated by EGF via ERK1/2 signaling and suppresses human epithelial
      ovarian cancer cell migration.
AB  - Although epithelial cell adhesion molecule (EpCAM) is overexpressed in human
      epithelial ovarian cancer (EOC), some contradictory results have been reported
      regarding the correlation between EpCAM overexpression and patient survival. In
      addition to this controversy, the function and regulation of EpCAM in EOC remain
      largely unknown. Here, we show that epidermal growth factor (EGF) up-regulates
      EpCAM expression by activating ERK1/2 signaling in a human EOC cell line, SKOV3.
      Additionally, EpCAM overexpression suppresses not only basal but also EGF
      stimulated SKOV3 cell migration, whereas EpCAM knockdown increases both basal and
      EGF-stimulated cell migration in another human EOC cell line, OVCAR4. This study
      demonstrates the regulation of EpCAM and its role in mediating the effects of EGF
      on human EOC cell migration. 

PMID- 25576359
TI  - On the tubulin polymerization promoting proteins of zebrafish.
AB  - Recently, Aoki et al. [15] have been published a paper (Biochem. Biophys. Res.
      Commun. 445 (2014) 357-362.) in which they identified possible downstream genes
      required for the extension of peripheral axons in primary sensory neurons of
      zebrafish. Tppp was claimed as one of them but, as I show, it is the tppp3-like
      gene, a paralog of tppp, which plays this role. There are three tppp paralogs in
      fishes: tppp1 (named also tppp), tppp3 and tppp3-like. Tppp1 and tppp3 are the
      orthologs of the corresponding human genes, however, the classification of the
      third one is ambiguous. It is known that the genomes of the early vertebrate
      lineage underwent two complete genome duplications, which result in the presence
      of several paralogs in vertebrates. A teleost fish specific third whole genome
      duplication also occurred. Thus the tppp3-like gene can be either an ortholog of
      human TPPP2 or a fourth paralog (tppp4) absent in tetrapods but present in
      fishes; finally a tppp3a gene which can be originated from the third, fish
      specific, whole genome duplication. Comparing the sequences of vertebrate and
      recently available lamprey tppps I show that the tppp3-like gene is a TPPP2
      ortholog. Synteny data are in accordance with this suggestion.

PMID- 25576360
TI  - miR-25 modulates NSCLC cell radio-sensitivity through directly inhibiting BTG2
      expression.
AB  - A large proportion of the NSCLC patients were insensitive to radiotherapy, but
      the exact mechanism is still unclear. This study explored the role of miR-25 in
      regulating sensitivity of NSCLC cells to ionizing radiation (IR) and its
      downstream targets. Based on measurement in tumor samples from NSCLC patients,
      this study found that miR-25 expression is upregulated in both NSCLC and radio
      resistant NSCLC patients compared the healthy and radio-sensitive controls. In
      addition, BTG expression was found negatively correlated with miR-25a expression
      in the both tissues and cells. By applying luciferase reporter assay, we verified
      two putative binding sites between miR-25 and BTG2. Therefore, BTG2 is a directly
      target of miR-25 in NSCLC cancer. By applying loss-and-gain function analysis in
      NSCLC cell lines, we demonstrated that miR-25-BTG2 axis could directly regulated
      BTG2 expression and affect radiotherapy sensitivity of NSCLC cells. 

PMID- 25576361
TI  - A bidirectional drug repositioning approach for Parkinson's disease through
      network-based inference.
AB  - Parkinson's Disease (PD) is one of the most prevailing neurodegenerative
      disorders. Novel computational approaches are required to find new ways of using
      the existing drugs or drug repositioning, as currently there exists no cure for
      PD. We proposed a new bidirectional drug repositioning method that consists of
      Top-down and Bottom-up approaches and finally gives information about significant
      repositioning drug candidates. This method takes into account of the topological
      significance of drugs in the tripartite Indication-drug-target network (IDTN) as
      well the significance of their targets in the PD-specific protein-protein
      interaction network (PPIN). 9 non-Parkinsonian drugs have been proposed as the
      significant repositioning candidates for PD. In order to find out the efficiency
      of the repositioning candidates we introduced a parameter called the On-target
      ratio (OTR). The average OTR value of final repositioning candidates has been
      found to be higher than that of known PD specific drugs. 

PMID- 25576362
TI  - Systematic drug safety evaluation based on public genomic expression
      (Connectivity Map) data: myocardial and infectious adverse reactions as
      application cases.
AB  - Adverse drug reaction (ADR) is of great importance to both regulatory agencies
      and the pharmaceutical industry. Various techniques, such as quantitative
      structure-activity relationship (QSAR) and animal toxicology, are widely used to
      identify potential risks during the preclinical stage of drug development.
      Despite these efforts, drugs with safety liabilities can still pass through
      safety checkpoints and enter the market. This situation raises the concern that
      conventional chemical structure analysis and phenotypic screening are not
      sufficient to avoid all clinical adverse events. Genomic expression data
      following in vitro drug treatments characterize drug actions and thus have become
      widely used in drug repositioning. In the present study, we explored prediction
      of ADRs based on the drug-induced gene-expression profiles from cultured human
      cells in the Connectivity Map (CMap) database. The results showed that drugs
      inducing comparable ADRs generally lead to similar CMap expression profiles.
      Based on such ADR-gene expression association, we established prediction models
      for various ADRs, including severe myocardial and infectious events. Drugs with
      FDA boxed warnings of safety liability were effectively identified. We therefore
      suggest that drug-induced gene expression change, in combination with effective
      computational methods, may provide a new dimension of information to facilitate
      systematic drug safety evaluation.

PMID- 25576351
TI  - Baseline feature of a randomized trial assessing the effects of disease
      management programs for the prevention of recurrent ischemic stroke.
AB  - BACKGROUND: Comprehensive and long-term patient education programs designed to
      improve self-management can help patients better manage their medical condition.
      Using disease management programs (DMPs) that were created for each of the risk
      factor according to clinical practice guidelines, we evaluate their influence on
      the prevention of stroke recurrence. METHODS: This is a randomized study
      conducted with ischemic stroke patients within 1 year from their onset. Subjects
      in the intervention group received a 6-month DMPs that included self-management
      education provided by a nurse along with support in collaboration with the
      primary care physician. Those in the usual care group received ordinary
      outpatient care. The primary end points are stroke recurrence and stroke death.
      Patients were enrolled for 2 years with plans for a 2-year follow-up after the 6
      month education period (total of 30 months). RESULTS: A total of 321 eligible
      subjects (average age, 67.3 years; females, 96 [29.9%]), including 21 subjects
      (6.5%) with transient ischemic attack, were enrolled in this study. Regarding
      risk factors for stroke, 260 subjects (81.0%) had hypertension, 249 subjects
      (77.6%) had dyslipidemia, 102 subjects (31.8%) had diabetes mellitus, 47 subjects
      (14.6%) had atrial fibrillation, and 98 subjects (30.5%) had chronic kidney
      disease. There were no significant differences between the 2 groups with respect
      to subject characteristics. CONCLUSIONS: This article describes the rationale,
      design, and baseline features of a randomized controlled trial that aimed to
      assess the effects of DMPs for the secondary prevention of stroke. Subject follow
      up is in progress and will end in 2015.

PMID- 25576363
TI  - Cold tolerance of the Antarctic nematodes Plectus murrayi and Scottnema
      lindsayae.
AB  - The cold tolerance of the Antarctic nematodes Scottnema lindsayae and Plectus
      murrayi was determined using material freshly isolated from the field. Both
      species could survive low temperatures but the survival of S. lindsayae was
      greater than that of P. murrayi. Field soil temperatures in late spring-early
      summer indicated a minimum temperature of -19.5  degrees C and a maximum cooling
      rate of 0.71  degrees C min(-1). In P. murrayi grown in culture, there was no
      significant effect of acclimation, nor of the two culture media used, on survival
      after freezing but survival was greater if freezing was seeded at -1  degrees C
      than at lower temperatures. The freezing survival ability of P. murrayi is much
      less than that of Panagrolaimus davidi CB1, another Antarctic nematode.
      Cryomicroscopy indicates that P. murrayi can survive low temperatures by either
      cryoprotective dehydration or freezing tolerance, but that freezing tolerance is
      the dominant strategy. Measurable thermal hysteresis was detected only in highly
      concentrated extracts of the nematodes, indicating the presence of an antifreeze
      protein, but at the concentrations likely to be found in vivo, the major function
      of the ice active protein involved is probably recrystallization inhibition. 

PMID- 25576364
TI  - A Burst of miRNA Innovation in the Early Evolution of Butterflies and Moths.
AB  - MicroRNAs (miRNAs) are involved in posttranscriptional regulation of gene
      expression. Because several miRNAs are known to affect the stability or
      translation of developmental regulatory genes, the origin of novel miRNAs may
      have contributed to the evolution of developmental processes and morphology.
      Lepidoptera (butterflies and moths) is a species-rich clade with a well
      established phylogeny and abundant genomic resources, thereby representing an
      ideal system in which to study miRNA evolution. We sequenced small RNA libraries
      from developmental stages of two divergent lepidopterans, Cameraria ohridella
      (Horse chestnut Leafminer) and Pararge aegeria (Speckled Wood butterfly),
      discovering 90 and 81 conserved miRNAs, respectively, and many species-specific
      miRNA sequences. Mapping miRNAs onto the lepidopteran phylogeny reveals rapid
      miRNA turnover and an episode of miRNA fixation early in lepidopteran evolution,
      implying that miRNA acquisition accompanied the early radiation of the
      Lepidoptera. One lepidopteran-specific miRNA gene, miR-2768, is located within an
      intron of the homeobox gene invected, involved in insect segmental and wing
      patterning. We identified cubitus interruptus (ci) as a likely direct target of
      miR-2768, and validated this suppression using a luciferase assay system. We
      propose a model by which miR-2768 modulates expression of ci in the segmentation
      pathway and in patterning of lepidopteran wing primordia. 

PMID- 25576365
TI  - The relationship between dN/dS and scaled selection coefficients.
AB  - Numerous computational methods exist to assess the mode and strength of natural
      selection in protein-coding sequences, yet how distinct methods relate to one
      another remains largely unknown. Here, we elucidate the relationship between two
      widely used phylogenetic modeling frameworks: dN/dS models and mutation-selection
      (MutSel) models. We derive a mathematical relationship between dN/dS and scaled
      selection coefficients, the focal parameters of MutSel models, and use this
      relationship to gain deeper insight into the behaviors, limitations, and
      applicabilities of these two modeling frameworks. We prove that, if all
      synonymous changes are neutral, standard MutSel models correspond to dN/dS <= 1.
      However, if synonymous codons differ in fitness, dN/dS can take on arbitrarily
      high values even if all selection is purifying. Thus, the MutSel modeling
      framework cannot necessarily accommodate positive, diversifying selection, while
      dN/dS cannot distinguish between purifying selection on synonymous codons and
      positive selection on amino acids. We further propose a new benchmarking strategy
      of dN/dS inferences against MutSel simulations and demonstrate that the widely
      used Goldman-Yang-style dN/dS models yield substantially biased dN/dS estimates
      on realistic sequence data. In contrast, the less frequently used Muse-Gaut-style
      models display much less bias. Strikingly, the least-biased and most precise
      dN/dS estimates are never found in the models with the best fit to the data,
      measured through both AIC and BIC scores. Thus, selecting models based on
      goodness-of-fit criteria can yield poor parameter estimates if the models
      considered do not precisely correspond to the underlying mechanism that generated
      the data. In conclusion, establishing mathematical links among modeling
      frameworks represents a novel, powerful strategy to pinpoint previously
      unrecognized model limitations and strengths.

PMID- 25576366
TI  - Regulation of splicing factors by alternative splicing and NMD is conserved
      between kingdoms yet evolutionarily flexible.
AB  - Ultraconserved elements, unusually long regions of perfect sequence identity, are
      found in genes encoding numerous RNA-binding proteins including arginine-serine
      rich (SR) splicing factors. Expression of these genes is regulated via
      alternative splicing of the ultraconserved regions to yield mRNAs that are
      degraded by nonsense-mediated mRNA decay (NMD), a process termed unproductive
      splicing (Lareau et al. 2007; Ni et al. 2007). As all human SR genes are affected
      by alternative splicing and NMD, one might expect this regulation to have
      originated in an early SR gene and persisted as duplications expanded the SR
      family. But in fact, unproductive splicing of most human SR genes arose
      independently (Lareau et al. 2007). This paradox led us to investigate the origin
      and proliferation of unproductive splicing in SR genes. We demonstrate that
      unproductive splicing of the splicing factor SRSF5 (SRp40) is conserved among all
      animals and even observed in fungi; this is a rare example of alternative
      splicing conserved between kingdoms, yet its effect is to trigger mRNA
      degradation. As the gene duplicated, the ancient unproductive splicing was lost
      in paralogs, and distinct unproductive splicing evolved rapidly and repeatedly to
      take its place. SR genes have consistently employed unproductive splicing, and
      while it is exceptionally conserved in some of these genes, turnover in specific
      events among paralogs shows flexible means to the same regulatory end. 

PMID- 25576368
TI  - Differential effects of short- and long-term antipsychotic treatment on the
      expression of neuregulin-1 and ErbB4 receptors in the rat brain.
AB  - Neuregulin-1 (NRG1) and ErbB4 genes have been identified as candidate genes for
      schizophrenia. Post-mortem studies indicated that NRG1-ErbB4 signalling is
      impaired in schizophrenia subjects. This study investigated whether short- or
      long-term antipsychotic treatment has different effects on the expression of NRG1
      and ErbB4 receptors. Female Sprague-Dawley rats were treated orally with either
      aripiprazole (0.75 mg/kg), haloperidol (0.1 mg/kg), olanzapine (0.5 mg/kg), or
      vehicle, 3 times/day for 1 or 12 weeks. Western blotting was performed to examine
      the expression of NRG1 isoforms (135 kDa, 70 kDa and 40 kDa) and ErbB4 receptors.
      Both 1-week haloperidol and olanzapine treatment increased NRG1-70kDa expression
      in the hippocampus; haloperidol also up-regulated ErbB4 levels in the prefrontal
      cortex (PFC). In the 12-week group, aripiprazole decreased the expression of all
      three NRG1 isoforms and ErbB4 receptors in the PFC, NRG1-70 kDa and -40 kDa in
      the cingulate cortex (Cg), and NRG1-135 kDa, -70 kDa and ErbB4 receptors in the
      hippocampus; haloperidol reduced NRG1-135 kDa in the PFC, NRG1-40 kDa in all
      three brain regions, and ErbB4 receptor levels in the PFC and hippocampus; NRG1
      40 kDa in the PFC and Cg was also down-regulated by olanzapine. These results
      suggest that the time-dependent and region-specific effects of antipsychotics on
      NRG1-ErbB4 signalling may contribute to the efficacy of antipsychotics to treat
      schizophrenia.

PMID- 25576367
TI  - Comorbid substance use disorders in schizophrenia: a latent class approach.
AB  - Schizophrenia is a complex psychiatric disorder with a characteristic disease
      course and heterogeneous etiology. While substance use disorders and a family
      history of psychosis have individually been identified as risk factors for
      schizophrenia, it is less well understood if and how these factors are related.
      To address this deficiency, we examined the relationship between substance use
      disorders and family history of psychosis in a sample of 1219 unrelated patients
      with schizophrenia. The lifetime rate of substance use disorders in this sample
      was 50%, and 30% had a family history of psychosis. Latent class mixture modeling
      identified three distinct patient subgroups: (1) individuals with low probability
      of substance use disorders; (2) patients with drug and alcohol abuse, but no
      symptoms of dependence; and (3) patients with substance dependence. Substance use
      was related to being male, to a more severe disease course, and more acute
      symptoms at assessment, but not to an earlier age of onset of schizophrenia or a
      specific pattern of positive and negative symptoms. Furthermore, substance use in
      schizophrenia was not related to a family history of psychosis. The results
      suggest that substance use in schizophrenia is an independent risk factor for
      disease severity and onset. 

PMID- 25576369
TI  - Is obsessive-compulsive symptomatology a risk factor for Alzheimer-type dementia?
AB  - In the present study, we hypothesized that lifetime Obsessive-Compulsive (OC)
      symptomatology would be risk factors for the development of Alzheimer's disease
      (AD). For this aim, first we compared 39 patients with AD and 30 age and gender
      matched control subjects. We have found that lifetime and current OC symptoms
      (OCs) and comorbid diagnosis of Obsessive-Compulsive Personality Disorder in AD
      patients were significantly more prevalent than in control group. AD patients had
      more likely to have lifetime and current hoarding, and checking obsessions
      compared to controls. The rate of lifetime and current hoarding, and checking
      compulsions also appeared to be higher in AD patients in comparison to control
      subjects. Hoarding and checking obsessions, and compulsions seemed to proceed
      through the dementia in contrast to other OCs. The mean number of lifetime
      compulsions seemed to predict the diagnosis of AD. When we compared AD patients
      with and without OCs, we have found that OC symptomatology prior to AD did not
      cause an earlier onset of dementia and more severe cognitive impairment. Further
      longitudinal clinical, genetic and neuroimaging investigations are required to
      determine if lifetime presence of OCs would predispose to the development of
      later AD. 

PMID- 25576370
TI  - Social feeding in Caenorhabditis elegans is modulated by antipsychotic drugs and
      calmodulin and may serve as a protophenotype for asociality.
AB  - Here, we define a protophenotype as an endophenotype that has been conserved
      during evolution. Social feeding in Caenorhabditis elegans may be an example of a
      protophenotype related to asociality in schizophrenia. It is regulated by the
      highly conserved neuropeptide Y receptor, NPR-1, and we speculated that social
      feeding should be affected by antipsychotic drugs. The social feeding strain, npr
      1(g320), was exposed to antipsychotic drugs, dopamine or calmodulin antagonists
      on plates with bacterial lawns, and the number of aggregates on the plates was
      counted as a measure of social feeding. First-generation antipsychotics,
      chlorpromazine, trifluoperazine, fluphenazine, and haloperidol, and the second
      generation drug, olanzapine, inhibited social feeding. Dopamine accelerated
      aggregation, whereas selective D2 dopamine receptor antagonists, sulpiride and
      raclopride, were inhibitory. Calmodulin antagonists effectively inhibited social
      feeding, as did RNAi knockdown of calmodulin (cmd-1) expression. In addition, gap
      junction inhibitors prevented aggregation, which is consistent with the hub-and
      spoke arrangement of neurons that regulate social feeding via functional gap
      junctions. The studies described here revealed novel connections between
      dopaminergic signaling, the NPY receptor, calmodulin, and gap junctions in the
      regulation of social behavior in C. elegans. These pathways are evolutionarily
      conserved, and have also been implicated in the pathogenesis of schizophrenia.

PMID- 25576372
TI  - Decreased in vivo alpha2 adrenoceptor binding in the Flinders Sensitive Line rat
      model of depression.
AB  - Depression is a debilitating heterogeneous disorder and the underlying mechanisms
      remain elusive. Alterations in monoaminergic neurotransmission, including
      noradrenergic, have been implicated in the etiology of depression. Although
      depression is difficult to model in animals, the availability of animal models
      with face, predictive and construct validity permits more in-depth investigations
      resulting in a greater understanding of the disease. We investigated the role of
      noradrenaline (NA) and alpha2 adrenoceptors in vivo in a genetic model of
      depression, the Flinders Sensitive Line (FSL) rat. We determined baseline
      differences in NA receptor volume of distribution to alpha2 adrenoceptors in FSL,
      in comparison with two routinely used controls, Flinders Resistant Line (FRL) and
      Sprague-Dawley (SD) rats using positron emission tomography (PET) imaging and the
      carbon-11 labeled radioligand yohimbine. We demonstrate a 42-47% reduction in the
      binding of the tracer in the cortex, striatum, cerebellum, thalamus and pons of
      FSL rats compared to the two control groups. Our results suggest that the
      behavioral deficits expressed in the FSL depression model are associated with
      functional over-activity of the NA system.

PMID- 25576371
TI  - Anisomycin in the medial prefrontal cortex reduces reconsolidation of cocaine
      associated memories in the rat self-administration model.
AB  - We tested the hypothesis that infusion of anisomycin into the medial prefrontal
      cortex (mPFC) disrupts the reconsolidation of a cocaine-associated memory in the
      rat cocaine self-administration model. Male Sprague-Dawley rats were trained to
      lever press for cocaine self-administration (0.5 mg/kg/infusion) along with a cue
      light presentation on an FR1 followed by an FR3 schedule of reinforcement for 2
      h/day. Rats were then given extinction sessions or an equivalent forced
      abstinence period followed by a 5 min memory reactivation session during which
      time they received an ip cocaine injection (10 mg/kg, ip) and were allowed to
      press for contingent cue light presentation. Immediately after reactivation, they
      were administered an intra-mPFC infusion of vehicle or anisomycin. Two additional
      control groups received extinction and either no memory reactivation and intra
      mPFC infusions as above or intra-mPFC infusions 6 h after memory reactivation. A
      fourth group received forced abstinence and intra-mPFC infusions immediately
      after memory reactivation. Combined cocaine + cue-induced reinstatement was given
      2-3 days (early) and 8-12 days (late) later. Rats given anisomycin in the
      Extinction + Reactivation demonstrated decreased reinstatement, while anisomycin
      treatment did not alter behavior in any of the other three groups. These results
      suggest that extinction training may recruit the mPFC such that it renders the
      memory susceptible to disruption by anisomycin. These findings have implications
      for using extinction training prior to or in conjunction with other therapies,
      including reconsolidation disruption, to enhance prefrontal control over drug
      seeking behavior.

PMID- 25576375
TI  - Plastic reconstructive and esthetic surgery and tobacco, a legal approach.
AB  - Tobacco is a supplementary surgical risk factor to which some of our patients
      expose themselves. A patient who smokes incurs a heightened risk of medical
      accident. This is now accepted scientific knowledge, and no currently practicing
      plastic surgeon can be unaware of the close connection between smoking and
      postoperative cutaneous healing complications. On this subject, surgeons are
      invested with a duty to advise. And when a patient continues to smoke, a
      physician can refuse to operate, except in the event of an emergency. In some
      cases, however, he can go ahead with the operation, provided that his analysis of
      the risk/benefit highlights the interest of the surgery for the patient, whatever
      may be the tobacco-related complications. It is nonetheless necessary that the
      latter be preliminary informed and that he or she knowingly accept the risk. 

PMID- 25576374
TI  - Fluoxetine treatment reverses the intergenerational impact of maternal separation
      on fear and anxiety behaviors.
AB  - Early life stress increases risks of fear and anxiety related disorders in
      adulthood, which may be alleviated by fluoxetine treatment. However, the
      intergenerational impacts of maternal separation (MS) on fear and anxiety
      behaviors from father to their offspring are little known. And the potential
      effects of fluoxetine treatment on the intergenerational transmission have not
      been well tested. Here, we investigated whether fluoxetine can reverse the
      intergenerational effects of MS on fear and anxiety behaviors. The first
      generation (F1) male rats were exposed to MS 3 h daily from postnatal day 2-14
      and then treated with fluoxetine for four weeks during adulthood before fear
      conditioning. We found that maternal separation significantly impaired contextual
      fear extinction in F1 adult male rats but not in their second generation (F2).
      Although no obvious effects of MS on anxiety were observed in F1 male rats, the
      F2 offspring displayed a phenotype of low anxiety-like behaviors despite they
      were reared in normal condition. Fluoxetine treatment in F1 males not only
      reversed the impairment of fear extinction in F1 males but also the low anxiety
      like behaviors in their F2 offspring. These findings highlight the
      intergenerational impacts of early life stress on fear and anxiety behaviors, and
      provide a new sight of the intergenerational effect of fluoxetine therapy for
      early life stress related mental problems.

PMID- 25576373
TI  - Differential effects of the dopamine D3 receptor antagonist PG01037 on cocaine
      and methamphetamine self-administration in rhesus monkeys.
AB  - The dopamine D3 receptor (D3R) has been shown to mediate many of the behavioral
      effects of psychostimulants associated with high abuse potential. This study
      extended the assessment of the highly selective D3R antagonist PG01037 on cocaine
      and methamphetamine (MA) self-administration to include a food-drug choice
      procedure. Eight male rhesus monkeys (n=4/group) served as subjects in which
      complete cocaine and MA dose-response curves were determined daily in each
      session. When choice was stable, monkeys received acute and five-day treatment of
      PG01037 (1.0-5.6 mg/kg, i.v.). Acute administration of PG01037 was effective in
      reallocating choice from cocaine to food and decreasing cocaine intake, however,
      tolerance developed by day 5 of treatment. Up to doses that disrupted responding,
      MA choice and intake were not affected by PG01037 treatment. PG01037 decreased
      total reinforcers earned per session and the behavioral potency was significantly
      greater on MA-food choice compared to cocaine-food choice. Furthermore, the acute
      efficacy of PG01037 was correlated with the sensitivity of the D3/D2R agonist
      quinpirole to elicit yawning. These data suggest (1) that efficacy of D3R
      compounds in decreasing drug choice is greater in subjects with lower D3R,
      perhaps suggesting that it is percent occupancy that is the critical variable in
      determining efficacy and (2) differences in D3R activity in chronic cocaine vs.
      MA users. Although tolerance developed to the effects of PG01037 treatment on
      cocaine choice, tolerance did not develop to the disruptive effects on food
      maintained responding. These findings suggest that combination treatments that
      decrease cocaine-induced elevations in DA may enhance the efficacy of D3R
      antagonists on cocaine self-administration.

PMID- 25576376
TI  - Smoking or not smoking? That is the question.

PMID- 25576377
TI  - Fungal necrotizing fasciitis, an emerging infectious disease caused by
      Apophysomyces (Mucorales).
AB  - BACKGROUND: The mucoralean fungi are emerging causative agents of primary
      cutaneous infections presenting in the form of necrotizing fasciitis. AIMS: The
      aim of this study was to investigate a series of suspected necrotizing fasciitis
      cases by Apophysomyces species over one-year period in a northern Indian
      hospital. METHODS: The clinical details of those patients suspected to suffer
      from fungal necrotizing fasciitis were recorded. Skin biopsies from local wounds
      were microscopically examined and fungal culturing was carried out on standard
      media. The histopathology was evaluated using conventional methods and special
      stains. Apophysomyces isolates were identified by their morphology and by
      molecular sequencing of the internal transcribed spacer (ITS) region of the
      ribosomal genes. Antifungal susceptibility testing was carried out following
      EUCAST guidelines and treatment progress was monitored. RESULTS: Seven patients
      were found to be suffering from necrotizing fasciitis caused by Apophysomyces
      spp. Six isolates were identified as Apophysomyces variabilis and one as
      Apophysomyces elegans. Five patients had previously received intramuscular
      injections in the affected area. Three patients recovered, two died and the other
      two left treatment against medical advice and are presumed to have died due to
      their terminal illnesses. Posaconazole and terbinafine were found to be the most
      active compounds against A. variabilis, while the isolate of A. elegans was
      resistant to all antifungals tested. CONCLUSIONS: Apophysomyces is confirmed as
      an aggressive fungus able to cause fatal infections. All clinicians,
      microbiologists and pathologists need to be aware of these emerging mycoses as
      well as of the risks involved in medical practices, which may provoke serious
      fungal infections such as those produced by Apophysomyces.

PMID- 25576379
TI  - Perception of the material properties of wood based on vision, audition, and
      touch.
AB  - Most research on the multimodal perception of material properties has
      investigated the perception of material properties of two modalities such as
      vision-touch, vision-audition, audition-touch, and vision-action. Here, we
      investigated whether the same affective classifications of materials can be found
      in three different modalities of vision, audition, and touch, using wood as the
      target object. Fifty participants took part in an experiment involving the three
      modalities of vision, audition, and touch, in isolation. Twenty-two different
      wood types including genuine, processed, and fake were perceptually evaluated
      using a questionnaire consisting of twenty-three items (12 perceptual and 11
      affective). The results demonstrated that evaluations of the affective properties
      of wood were similar in all three modalities. The elements of "expensiveness,
      sturdiness, rareness, interestingness, and sophisticatedness" and "pleasantness,
      relaxed feelings, and liked-disliked" were separately grouped for all three
      senses. Our results suggest that the affective material properties of wood are at
      least partly represented in a supramodal fashion. Our results also suggest an
      association between perceptual and affective properties, which will be a useful
      tool not only in science, but also in applied fields. 

PMID- 25576378
TI  - Norm-based coding of facial identity in adults with autism spectrum disorder.
AB  - It is unclear whether reported deficits in face processing in individuals with
      autism spectrum disorders (ASD) can be explained by deficits in perceptual face
      coding mechanisms. In the current study, we examined whether adults with ASD
      showed evidence of norm-based opponent coding of facial identity, a perceptual
      process underlying the recognition of facial identity in typical adults. We began
      with an original face and an averaged face and then created an anti-face that
      differed from the averaged face in the opposite direction from the original face
      by a small amount (near adaptor) or a large amount (far adaptor). To test for
      norm-based coding, we adapted participants on different trials to the near versus
      far adaptor, then asked them to judge the identity of the averaged face. We
      varied the size of the test and adapting faces in order to reduce any
      contribution of low-level adaptation. Consistent with the predictions of norm
      based coding, high functioning adults with ASD (n = 27) and matched typical
      participants (n = 28) showed identity aftereffects that were larger for the far
      than near adaptor. Unlike results with children with ASD, the strength of the
      aftereffects were similar in the two groups. This is the first study to
      demonstrate norm-based coding of facial identity in adults with ASD.

PMID- 25576380
TI  - Visual discomfort and the spatial distribution of Fourier energy.
AB  - Quite independently of what they represent, some images provoke discomfort, and
      even headaches and seizures in susceptible individuals. The visual system has
      adapted to efficiently process the images it typically experiences, and in nature
      these images are usually scale-invariant. In this work, we sought to characterize
      the images responsible for discomfort in terms of their adherence to low-level
      statistical properties typically seen in natural scenes. It has been conventional
      to measure scale invariance in terms of the one-dimensional Fourier amplitude
      spectrum, by averaging amplitude over orientations in the Fourier domain.
      However, this loses information on the evenness with which information at various
      orientations is represented. We therefore fitted a two-dimensional surface
      (regular circular cone 1/f in logarithmic coordinates) to the two-dimensional
      amplitude spectrum. The extent to which the cone fitted the spectrum explained an
      average of 18% of the variance in judgments of discomfort from images including
      rural and urban scenes, works of non-representational art, images of buildings
      and animals, and images generated from randomly disposed discs of varying
      contrast and size. Weighting the spectrum prior to fitting the surface to allow
      for the spatial frequency tuning of contrast sensitivity explained an average of
      27% of the variance. Adjusting the shape of the cone to take account of the
      generally greater energy in horizontal and vertical orientations improved the
      fit, but only slightly. Taken together, our findings show that a simple measure
      based on first principles of efficient coding and human visual sensitivity
      explained more variance than previously published algorithms. The algorithm has a
      low computational cost and we show that it can identify the images involved in
      cases that have reached the media because of complaints. We offer the algorithm
      as a tool for designers rather than as a simulation of the biological processes
      involved. 

PMID- 25576381
TI  - C6 ceramide dramatically enhances docetaxel-induced growth inhibition and
      apoptosis in cultured breast cancer cells: a mechanism study.
AB  - Here we reported that co-administration of docetaxel and a cell-permeable short
      chain ceramide (C6) resulted in a striking increase in growth inhibition and
      apoptosis in primary and transformed breast cells (MCF-7 and MDA-231), which were
      associated with mitochondrial permeability transition pore (mPTP) opening, a
      significant reactive oxygen species (ROS) production and the pro-apoptotic AMP
      Protein Kinase (AMPK) as well as c-Jun N-terminal kinases (JNK) activations.
      Contrarily, the mPTP blocker sanglifehrin A (SfA) or the ROS scavenger N-acetyl-l
      cysteine (NAC) largely inhibited co-administration-induced cytotoxicity. Further,
      cyclosporin A (CsA), the inhibitor of cyclophilin-D (Cyp-D, the key mPTP
      component), as well as Cyp-D RNA silencing also suppressed breast cancer cell
      death by the co-treatment, while cells overexpressing Cyp-D showed
      hypersensitivity to docetaxel. Meanwhile, JNK and AMPK inhibition alleviated cell
      death induced by the co-administration in cultured breast cancer cells.
      Significantly, C6 ceramide plus docetaxel caused dramatic human epidermal growth
      factor receptor (HER)-1/-2 degradation and downstream Akt/Erk inhibition in HER-2
      expressing MDA-231 cells. These in vitro findings provide confidence in support
      of further development of C6 ceramide as an adjunct of docetaxel for the
      treatment of the metastatic breast cancer.

PMID- 25576382
TI  - Regulatory mechanisms that control mitotic kinesins.
AB  - During mitosis, the mitotic spindle is assembled to align chromosomes at the
      spindle equator in metaphase, and to separate the genetic material equally to
      daughter cells in anaphase. The spindle itself is a macromolecular machine
      composed of an array of dynamic microtubules and associated proteins that
      coordinate the diverse events of mitosis. Among the microtubule associated
      proteins are a plethora of molecular motor proteins that couple the energy of ATP
      hydrolysis to force production. These motors, including members of the kinesin
      superfamily, must function at the right time and in the right place to insure the
      fidelity of mitosis. Misregulation of mitotic motors in disease states, such as
      cancer, underlies their potential utility as targets for antitumor drug
      development and highlights the importance of understanding the molecular
      mechanisms for regulating their function. Here, we focus on recent progress about
      regulatory mechanisms that control the proper function of mitotic kinesins and
      highlight new findings that lay the path for future studies. 

PMID- 25576383
TI  - Distinct functional roles of cytoplasmic dynein defined by the intermediate chain
      isoforms.
AB  - The motor protein, cytoplasmic dynein is responsible for the movement of a
      variety of cargoes toward microtubule minus ends in cells. Little is understood
      about how dynein is regulated to specifically transport its various cargoes. In
      vertebrates, the dynein motor domain (DYNC1H) is encoded by a single gene; while
      there are two genes for the five smaller subunits that comprise the cargo binding
      domain of the dynein complex. The isoforms of the intermediate chain (DYNC1I)
      provide a good model system with which to study the roles the different isoforms
      of the cargo domain subunits have in designating specific dynein functions. The
      intermediate chains (DYNC1I) play a key scaffold role in the dynein complex. In
      neurons, dynein complexes with different intermediate chain isoforms have
      distinct roles, including cargo binding and transport. Some of the phospho
      isoforms of the intermediate chain also specify binding to specific cargo. These
      data support the model that cytoplasmic dynein can be specifically regulated
      through the different isoforms of the subunits. 

PMID- 25576384
TI  - Thymopentin enhances the generation of T-cell lineage derived from human
      embryonic stem cells in vitro.
AB  - Thymopentin is a group of biologically active peptide secreted mainly by the
      epithelial cells of thymic cortex and medulla. Whether it promotes T cells
      production from human embryonic stem cells(hESCs) in vitro remains an elusive
      issue. In the present study, we develop a novel strategy that enhances T-cell
      lineage differentiation of hESCs in collagen matrix culture by sequential
      cytokine cocktails treatment combined with thymopentin stimulation. We observed
      that approximately 30.75% cells expressed CD34 on day 14 of the cultures and
      expressed the surface markers of erythroid, lymphoid and myeloid lineages. The
      results of colony assays and gene expressions by RT-PCR analysis also
      demonstrated that hematopoietic progenitor cells (HPCs) derived from hESCs were
      capable of multi-lineage differentiation. Further study revealed that culturing
      with thymopentin treatment, the CD34(+)CD45RA(+)CD7(+) cells sorted from HPCs
      expressed T-cell-related genes, IKAROS, DNTT, TCRgamma and TCRbeta, and T-cell
      surface markers, CD3, cytoplasmic CD3, CD5, CD27, TCRgammadelta, CD4 and CD8. The
      differentiated cells produced the cytokines including IFN-gamma, IL-2 and TNF
      alpha in response to stimulation, providing the evidence for T-cell function of
      these cells. In conclusion, thymopentin enhances T-cell lineage differentiation
      from hESCs in vitro by mimicking thymus peptide environment in vivo.

PMID- 25576385
TI  - Scoparone attenuates RANKL-induced osteoclastic differentiation through
      controlling reactive oxygen species production and scavenging.
AB  - Scoparone, one of the bioactive components of Artemisia capillaris Thunb, has
      various biological properties including immunosuppressive, hepatoprotective, anti
      allergic, anti-inflammatory, and antioxidant effects. This study aims at
      evaluating the anti-osteoporotic effect of scoparone and its underlying mechanism
      in vitro. Scoparone demonstrated potent cellular antioxidant capacity. It was
      also found that scoparone inhibited the receptor activator of nuclear factor
      kappaB ligand (RANKL)-induced osteoclast differentiation and suppressed cathepsin
      K and tartrate-resistant acid phosphatase (TRAP) expression via c-jun N-terminal
      kinase (JNK)/extracellular signal-regulated kinase (ERK)/p38-mediated c-Fos
      nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway.
      During osteoclast differentiation, the production of general reactive oxygen
      species (ROS) and superoxide anions was dose-dependently attenuated by scoparone.
      In addition, scoparone diminished NADPH (nicotinamide adenine dinucleotide
      phosphate) oxidase 1 (Nox1) expression and activation via the tumor necrosis
      factor receptor-associated factor 6 (TRAF6)-cSrc-phosphatidylinositol 3-kinase
      (PI3k) signaling pathway and prevented the disruption of mitochondrial electron
      transport chain system. Furthermore, scoparone augmented the expression of
      superoxide dismutase 1 (SOD1) and catalase (CAT). The overall results indicate
      that the inhibitory effect of scoparone on RANKL-induced osteoclast
      differentiation is attributed to the suppressive effect on ROS and superoxide
      anion production by inhibiting Nox1 expression and activation and protecting the
      mitochondrial electron transport chain system and the scavenging effect of ROS
      resulting from elevated SOD1 and CAT expression.

PMID- 25576386
TI  - Silencing of nodal modulator 1 inhibits the differentiation of P19 cells into
      cardiomyocytes.
AB  - Nodal modulator 1 (NOMO1), a highly conserved transmembrane protein, has been
      identified as a part of a protein complex that participates in the Nodal
      signaling pathway, a critical determinant of heart and visceral organ formation.
      We previously found that the NOMO1 gene was substantially downregulated in human
      ventricular septal defect (VSD) myocardium and, thus, may be an important
      molecular pathway in human heart development. In this study, we aimed to
      investigate the effects of NOMO1 gene silencing by RNA interference (RNAi) during
      early mouse cardiac differentiation using P19 cells as a model system. Our
      results revealed that the differentiated P19 cell population exhibited
      downregulated NOMO1 levels and expressed lower levels of Nodal signaling
      mediators, such as Nodal, Cripto and Smad2, than the negative control. Similarly,
      cardiomyocyte-specific sarcomeric markers, such as cardiac troponin T, as well as
      expression of cardiogenesis-related transcriptional factors, such as Nkx2.5,
      Gata4 and Tbx5 were found to be downregulated in P19 differentiated
      cardiomyocytes in NOMO1-silenced cells when compared to controls. In conclusion,
      our results indicate that NOMO1 gene knockdown inhibits the differentiation of
      P19 cells into cardiomyocytes, which highlights a potential role for NOMO1 in
      early cardiogenesis.

PMID- 25576387
TI  - Author's response to: Acid-fast bacilli culture positivity and drug resistance in
      abdominal tuberculosis.

PMID- 25576388
TI  - A study of gender-wise risk association between fatty liver and metabolic
      syndrome components (Asia-Pacific criteria) in a South Indian urban cohort.
AB  - BACKGROUND: Metabolic syndrome (MS) is associated with fatty liver (FL) disease.
      Gender differences in this association are not known. AIM: The aim of the present
      study was to determine gender-wise association between FL and MS components
      (using Asia-Pacific guidelines 2007) in an urban south Indian cohort with normal
      liver function tests (LFT). METHODS: Records of consecutive attendees of a Master
      Health Check up program were reviewed for age, gender, body mass index (BMI),
      blood pressure, fasting blood sugar (FBS), high-density lipoproteins,
      triglyceride (TG) levels, presence of FL by ultrasound. The cohort was grouped
      gender-wise as FL and nonfatty liver (NFL). Foreign nationals; those with alcohol
      intake >20 g/day; and those with diabetes, hypertension, hypertriglyceridemia,
      chronic liver disease, or abnormal LFT were excluded. STATISTICS: Chi-square,
      gender-wise univariate and logistic regression analyses of each MS component for
      FL, relative risk (RR), and 95 % confidence interval (CI) for significant factors
      (p < 0.05 and RR or log odds >1.5) were calculated. RESULTS: Of the 1,075 (63 %
      males) cases included, 45.8 % had FL. Gender (log odds 1.6 compared to women) and
      BMI >=25 kg/m(2) (RR 1.6 % to 95 % CI 1.3 to 1.9; log odds 2.2) were the only
      factors associated with FL in men. In women, age >=40 years (log odds 2.3),
      fasting blood sugar (FBS) >=100 mg/dL (RR 1.8-1.4 to 2.3; log odds 1.9), and TG
      >=150 mg/dL (RR 1.7-1.3 to 2.1; log odds 1.7) were independently associated with
      FL. CONCLUSION: There was a gender-wise difference in MS components associated
      with hepatic steatosis and normal LFT in a south Indian urban cohort.

PMID- 25576389
TI  - Infectious bovine keratoconjunctivitis (pinkeye).
AB  - As is the case for controlling other infectious livestock diseases, the most
      successful efforts to control infectious bovine keratoconjunctivitis (IBK) will
      include consideration of the host, the environment, herd management, and ongoing
      surveillance even after the immediate crisis has passed. Research over many years
      has led to the discovery of a variety of antibiotic treatments and antibiotic
      regimens that can be effective against IBK. The discoveries of Mor bovoculi and
      reports of IBK associated with Mycoplasma spp without concurrent Mor bovis or Mor
      bovoculi have raised new questions into the roles that other organisms may play
      in IBK pathogenesis. 

PMID- 25576390
TI  - Pointwise characterization of the elastic properties of planar soft tissues:
      application to ascending thoracic aneurysms.
AB  - In this manuscript, we present a combined experimental and computational
      technique that can identify the heterogeneous elastic properties of planar soft
      tissues. By combining inverse membrane analysis, digital image correlation, and
      bulge inflation tests, we are able to identify a tissue's mechanical properties
      locally. To show how the proposed method could be implemented, we quantified the
      heterogeneous material properties of a human ascending thoracic aortic aneurysm
      (ATAA). The ATAA was inflated at a constant rate using a bulge inflation device
      until it ruptured. Every 3 kPa images were taken using a stereo digital image
      correlation system. From the images, the three-dimensional displacement of the
      sample surface was determined. A deforming NURBS mesh was derived from the
      displacement data, and the local strains were computed. The wall stresses at each
      pressure increment were determined using inverse membrane analysis. The local
      material properties of the ATAA were then identified using the pointwise stress
      and strain data. To show that it is necessary to consider the heterogeneous
      distribution of the mechanical properties in the ATAA, three different forward
      finite element simulations using pointwise, elementwise, and homogeneous material
      properties were compared. The forward finite element predictions revealed that
      heterogeneous nature of the ATAA must be accounted for to accurately reproduce
      the stress-strain response. 

PMID- 25576392
TI  - The challenges of developing effective anti-inflammatory agents in cystic
      fibrosis.

PMID- 25576391
TI  - The cost of hospital readmissions: evidence from the VA.
AB  - This paper is an examination of hospital 30-day readmission costs using data from
      119 acute care hospitals operated by the U.S. Veterans Administration (VA) in
      fiscal year 2011. We applied a two-part model that linked readmission probability
      to readmission cost to obtain patient level estimates of expected readmission
      cost for VA patients overall, and for patients discharged for three prevalent
      conditions with relatively high readmission rates. Our focus was on the variable
      component of direct patient cost. Overall, managers could expect to save $2140
      for the average 30-day readmission avoided. For heart attack, heart failure, and
      pneumonia patients, expected readmission cost estimates were $3432, $2488 and
      $2278. Patient risk of illness was the dominant driver of readmission cost in all
      cases. The VA experience has implications for private sector hospitals that treat
      a high proportion of chronically ill and/or low income patients, or that are
      contemplating adopting bundled payment mechanisms. 

PMID- 25576393
TI  - PPARalpha via HNF4alpha regulates the expression of genes encoding hepatic amino
      acid catabolizing enzymes to maintain metabolic homeostasis.
AB  - The liver is the main organ involved in the metabolism of amino acids (AA), which
      are oxidized by amino acid catabolizing enzymes (AACE). Peroxisome proliferator
      activated receptor-alpha (PPARalpha) stimulates fatty acid beta-oxidation, and
      there is evidence that it can modulate hepatic AA oxidation during the transition
      of energy fuels. To understand the role and mechanism of PPARalpha's regulation
      of AA catabolism, the metabolic and molecular adaptations of Ppara-null mice were
      studied. The role of PPARalpha on AA metabolism was examined by in vitro and in
      vivo studies. In wild-type and Ppara-null mice, fed increasing concentrations of
      the dietary protein/carbohydrate ratio, we measured metabolic parameters, and
      livers were analyzed by microarray analysis, histology and Western blot.
      Functional enrichment analysis, EMSA and gene reporter assays were performed.
      Ppara-null mice presented increased expression of AACE in liver affecting AA,
      lipid and carbohydrate metabolism. Ppara-null mice had increased glucagon/insulin
      ratio (7.2-fold), higher serum urea (73.1 %), lower body protein content (19.7 %)
      and decreased several serum AA in response to a high-protein/low-carbohydrate
      diet. A functional network of differentially expressed genes, suggested that
      changes in the expression of AACE were regulated by an interrelationship between
      PPARalpha and HNF4alpha. Our data indicated that the expression of AACE is down
      regulated through PPARalpha by attenuating HNF4alpha transcriptional activity as
      observed in the serine dehydratase gene promoter. PPARalpha via HNF4alpha
      maintains body protein metabolic homeostasis by down-regulating genes involved in
      amino acid catabolism for preserving body nitrogen. 

PMID- 25576394
TI  - Online learning and control of attraction basins for the development of
      sensorimotor control strategies.
AB  - Imitation and learning from humans require an adequate sensorimotor controller to
      learn and encode behaviors. We present the Dynamic Muscle Perception-Action(DM
      PerAc) model to control a multiple degrees-of-freedom (DOF) robot arm. In the
      original PerAc model, path-following or place-reaching behaviors correspond to
      the sensorimotor attractors resulting from the dynamics of learned sensorimotor
      associations. The DM-PerAc model, inspired by human muscles, permits one to
      combine impedance-like control with the capability of learning sensorimotor
      attraction basins. We detail a solution to learn incrementally online the DM
      PerAc visuomotor controller. Postural attractors are learned by adapting the
      muscle activations in the model depending on movement errors. Visuomotor
      categories merging visual and proprioceptive signals are associated with these
      muscle activations. Thus, the visual and proprioceptive signals activate the
      motor action generating an attractor which satisfies both visual and
      proprioceptive constraints. This visuomotor controller can serve as a basis for
      imitative behaviors. In addition, the muscle activation patterns can define
      directions of movement instead of postural attractors. Such patterns can be used
      in state-action couples to generate trajectories like in the PerAc model. We
      discuss a possible extension of the DM-PerAc controller by adapting the
      Fukuyori's controller based on the Langevin's equation. This controller can serve
      not only to reach attractors which were not explicitly learned, but also to learn
      the state/action couples to define trajectories. 

PMID- 25576395
TI  - Bursting activity of substantia nigra pars reticulata neurons in mouse
      parkinsonism in awake and anesthetized states.
AB  - Electrophysiological changes in basal ganglia neurons are hypothesized to
      underlie motor dysfunction in Parkinson's disease (PD). Previous results in head
      restrained MPTP-treated non-human primates have suggested that increased bursting
      within the basal ganglia and related thalamic and cortical areas may be a
      hallmark of pathophysiological activity. In this study, we investigated whether
      there is increased bursting in substantia nigra pars reticulata (SNpr) output
      neurons in anesthetized and awake, head-restrained unilaterally lesioned 6-OHDA
      mice when compared to control mice. Confirming previous studies, we show that
      there are significant changes in the firing rate and pattern in SNpr neuron
      activity under urethane anesthesia. The regular firing pattern of control
      urethane-anesthetized SNpr neurons was not present in the 6-OHDA-lesioned group,
      as the latter neurons instead became phase locked with cortical slow wave
      activity (SWA). Next, we examined whether such robust electrophysiological
      changes between groups carried over to the awake state. SNpr neurons from both
      groups fired at much higher frequencies in the awake state than in the
      anesthetized state and surprisingly showed only modest changes between awake
      control and 6-OHDA groups. While there were no differences in firing rate between
      groups in the awake state, an increase in the coefficient of variation (CV) was
      observed in the 6-OHDA group. Contrary to the bursting hypothesis, this increased
      CV was not due to changes in bursting but was instead due to a mild increase in
      pausing. Together, these results suggest that differences in SNpr activity
      between control and 6-OHDA lesioned mice may be strongly influenced by changes in
      network activity during different arousal and behavioral states. 

PMID- 25576396
TI  - Rescuable folding defective NaV1.1 (SCN1A) mutants in epilepsy: properties,
      occurrence, and novel rescuing strategy with peptides targeted to the endoplasmic
      reticulum.
AB  - Mutations of the voltage gated Na(+) channel Na(V)1.1 (SCN1A) are important
      causes of different genetic epilepsies and can also cause familial hemiplegic
      migraine (FHM-III). In previous studies, some rescuable epileptogenic folding
      defective mutants located in domain IV of Na(V)1.1 have been identified, showing
      partial loss of function also with maximal rescue. Variable rescue may be one of
      the causes of phenotypic variability, and rescue might be exploited for
      therapeutic approaches. Recently, we have identified a folding defective FHM-III
      Na(V)1.1 mutant that showed overall gain of function when rescued, consistent
      with a differential pathomechanism. Here, we have evaluated functional properties
      and cell surface expression of six Na(V)1.1 epileptogenic missense mutations in
      different rescuing conditions, including a novel one that we have developed
      expressing a selective sodium channel toxin (CsEI) targeted to the endoplasmic
      reticulum (ER). All the mutants showed loss of function and reduced cell surface
      expression, consistently with possibility of rescue. Four of them were rescuable
      by incubation at low temperature and interactions with different co-expressed
      proteins or a pharmacological chaperone (phenytoin). Notably, CsEI was able to
      rescue four mutants. Thus, Na(V)1.1 folding defective mutants can be relatively
      common and mutations inducing rescuable folding defects are spread in all
      Na(V)1.1 domains. Importantly, epileptogenic mutants showed overall loss of
      function even upon rescue, differently than FHM-III ones. The effectiveness of
      CsEI demonstrates that interactions in the ER are sufficient for inducing rescue,
      and provides a proof of concept for developing possible therapeutic approaches
      that may overcome some limitations of pharmacological chaperones.

PMID- 25576399
TI  - The National Injury Surveillance System in China: a six-year review.
AB  - INTRODUCTION: This article aims to describe the National Injury Surveillance
      System (NISS) in China from its establishment in 2006 to the methods used and
      some key findings from 2006 to 2011. METHODS: From 2003 to 2005, based upon
      specific injury case definitions, a pilot study was conducted to explore the
      feasibility of a National Injury Surveillance System (NISS) in China. The NISS
      formally started operations in January 2006, and 126 hospitals from 43 sample
      points (23 rural, 20 urban) were selected to participate. Doctors and nurses in
      participating hospitals were trained to administer standardised data collection
      forms. Chinese Center for Disease Control and Prevention is in charge of
      analysing data and releasing findings. RESULTS: From 2006 to 2011, the annual
      recorded injury cases increased from 340,000 to 630,000, the majority being male
      (65%) and over 80% aged 15-64 years. Falls (32%), road traffic injuries (23%) and
      blunt injuries (19%) were the most common causes. More than 70% of cases were of
      minor severity, and over 75% of cases were discharged after treatment in the
      emergency department. CONCLUSIONS: The NISS is the first hospital-based national
      system in China, therefore considered an important source of injury data. It has
      the potential to describe injury morbidity in China and to be utilised to develop
      national technical and policy documents.

PMID- 25576398
TI  - A discussion on the limits of carbon-fibres reinforced polymers prompted by a
      case of destruent synovitis in the wrist.

PMID- 25576400
TI  - Liraglutide as add-on therapy to insulin in type 2 diabetes mellitus: a
      retrospective, observational study from a daily clinical practice setting in
      Switzerland.
AB  - INTRODUCTION: In most patients with type 2 diabetes mellitus (T2DM) and
      progressive beta-cell insufficiency, insulin therapy is required to achieve
      sufficient glycemic control. However, insulin therapy may lead to weight gain and
      increasing risk of hypoglycemia. Glucagon-like peptide-1 receptor agonists are
      being used as add-on therapy to insulin with favorable metabolic effects.
      Nonetheless, to date only few studies exist reporting on the combination of
      liraglutide and insulin with a short follow-up period. The aim of this study was
      to evaluate the efficacy and safety of liraglutide as add-on to insulin in
      patients with T2DM over a time period of up to 24-28 months. METHODS: Data of
      patients with T2DM, treated with insulin and liraglutide at an outpatient clinic
      in a tertiary referral hospital from October 2009 until December 2011 were
      retrospectively examined (n = 36). Glycated hemoglobin (HbA1c), weight, total
      daily insulin dose and side effects were assessed 5-8 months prior to
      liraglutide, at baseline and at follow-up visits after 3, 6, 12-16 and 24-28
      months. RESULTS: Median HbA1c decreased significantly from 7.7% [interquartile
      range (IQR) 7.0-8.6] at baseline to 6.8% (IQR 6.5-7.7, p = 0.001) at 3 months and
      6.9% (IQR 6.3-7.6, p = 0.0001) at 6 months, but re-increased thereafter (at 24-28
      months, median 7.5%, IQR 7.1-8.2, p = 1.0). Median weight decreased significantly
      from 99.8 kg (IQR 81-110) at baseline to 97.7 kg (IQR 81.2-108.2, p = 0.027) at 3
      months, but rose again thereafter. Insulin dosage did not change significantly
      over time. No severe hypoglycemia or major side effects occurred. CONCLUSIONS: In
      this observational study, adding liraglutide to insulin in daily clinical
      practice reduced HbA1c significantly within 6 months, but there may be a non
      sustainable effect during long-term treatment.

PMID- 25576397
TI  - Pin1 cysteine-113 oxidation inhibits its catalytic activity and cellular function
      in Alzheimer's disease.
AB  - The unique proline isomerase Pin1 is pivotal for protecting against age-dependent
      neurodegeneration in Alzheimer's disease (AD), with its inhibition providing a
      molecular link between tangle and plaque pathologies. Pin1 is oxidatively
      modified in human AD brains, but little is known about its regulatory mechanisms
      and pathological significance of such Pin1 modification. In this paper, our
      determination of crystal structures of oxidized Pin1 reveals a series of Pin1
      oxidative modifications on Cys113 in a sequential fashion. Cys113 oxidization is
      further confirmed by generating antibodies specifically recognizing oxidized
      Cys113 of Pin1. Furthermore, Pin1 oxidation on Cys113 inactivates its catalytic
      activity in vitro, and Ala point substitution of Cys113 inactivates the ability
      of Pin1 to isomerize tau as well as to promote protein turnover of tau and APP.
      Moreover, redox regulation affects Pin1 subcellular localization and Pin1
      mediated neuronal survival in response to hypoxia treatment. Importantly, Cys113
      oxidized Pin1 is significantly increased in human AD brain comparing to age
      matched controls. These results not only identify a novel Pin1 oxidation site to
      be the critical catalytic residue Cys113, but also provide a novel oxidative
      regulation mechanism for inhibiting Pin1 activity in AD. These results suggest
      that preventing Pin1 oxidization might help to reduce the risk of AD. 

PMID- 25576401
TI  - Religious, Ethical and Legal Considerations in End-of-Life Issues: Fundamental
      Requisites for Medical Decision Making.
AB  - Religion and spirituality have always played a major and intervening role in a
      person's life and health matters. With the influential development of patient
      autonomy and the right to self-determination, a patient's religious affiliation
      constitutes a key component in medical decision making. This is particularly
      pertinent in issues involving end-of-life decisions such as withdrawing and
      withholding treatment, medical futility, nutritional feeding and do-not
      resuscitate orders. These issues affect not only the patient's values and
      beliefs, but also the family unit and members of the medical profession. The law
      also plays an intervening role in resolving conflicts between the sanctity of
      life and quality of life that are very much pronounced in this aspect of
      healthcare. Thus, the medical profession in dealing with the inherent ethical and
      legal dilemmas needs to be sensitive not only to patients' varying religious
      beliefs and cultural values, but also to the developing legal and ethical
      standards as well. There is a need for the medical profession to be guided on the
      ethical obligations, legal demands and religious expectations prior to handling
      difficult end-of-life decisions. The development of comprehensive ethical codes
      in congruence with developing legal standards may offer clear guidance to the
      medical profession in making sound medical decisions. 

PMID- 25576402
TI  - Paeoniflorin inhibits skin lesions in imiquimod-induced psoriasis-like mice by
      downregulating inflammation.
AB  - Psoriasis is a common chronic immune-mediated inflammatory disease. It is well
      known that macrophages, neutrophils and T-helper 1 (Th1)/T-helper 17 (Th17) cells
      play important roles in skin lesions by provoking inflammation. Paeoniflorin (PF)
      is the major effective component extracted from the root of Paeonia lactiflora,
      which has been widely used in China to treat inflammatory and autoimmune
      diseases, including psoriasis. Although PF shows a clinical therapeutic effect on
      psoriasis patients, how PF affects infiltrated immune cells in psoriasis skin
      lesions is still unknown. In this study, using a generated imiquimod (IMQ)
      induced psoriasis-like mouse model, we found that PF ameliorates inflammation and
      skin lesions. Subsequent analyses showed that PF decreases the number of
      F4/80(+)CD68(+) macrophages and their related cytokine production (TNF-alpha, IL
      1beta, IL-6, IL-12 and inducible nitric oxide synthase (iNOS)) in the skin of IMQ
      challenged mice. Moreover, PF suppresses the number of CD11b(+)Gr-1(+)
      neutrophils and the expression of macrophage inflammatory protein-2 (MIP-2; a
      counterpart of human IL-8, which is responsible for the recruitment of
      neutrophils in mice). Finally, PF also down-regulates Th1- and Th17-related
      cytokine expression. Therefore, our new findings reveal that PF alleviates
      psoriatic skin lesions by inhibiting inflammation, which provides new insights
      into the immunomodulatory effect of PF in psoriasis treatment. 

PMID- 25576403
TI  - Aucubin prevents interleukin-1 beta induced inflammation and cartilage matrix
      degradation via inhibition of NF-kappaB signaling pathway in rat articular
      chondrocytes.
AB  - Proinflammatory cytokine interleukin-1beta (IL-1beta) plays a crucial role in the
      pathogenesis of Osteoarthritis (OA) by stimulating several mediators contributed
      to cartilage degradation. Aucubin, a natural compound derived from plants which
      has been shown to possess diverse biological activities including anti
      inflammatory property, may benefit the IL-1beta stimulated chondrocytes. The
      present study was aimed to investigate the effects of Aucubin on IL-1beta
      stimulated rat chondrocytes. Rat chondrocytes were cultured and pretreated with
      Aucubin (1, 10, 20, 50MUM), and then stimulated with or without IL-1beta
      (10ng/ml). Gene and protein expression of MMP-3, MMP-9, MMP-13, cyclooxygenase-2
      (COX-2), inducible nitric oxide synthase (iNOS) was determined by real-time PCR
      and Western blotting respectively. Nitric oxide (NO) production was quantified by
      Griess reagent. Phosphorylation and nuclear translocation of p65 were detected by
      western blotting and immunofluorescence, respectively. We found that Aucubin
      significantly reversed the elevated gene and protein expression of MMP-3, MMP-9,
      MMP-13, iNOS, COX-2 and the production of NO induced by IL-1beta challenge in rat
      chondrocytes. Furthermore, Aucubin was able to suppress the IL-1beta-mediated
      phosphorylation and nuclear translocation of p65, indicating Aucubin may possibly
      act via the NF-kappaB signaling pathway. The present study proposes that Aucubin
      may be a potential therapeutic choice in the treatment of OA due to its anti
      inflammatory and chondroprotective features. 

PMID- 25576405
TI  - President's page: Worldwide expansion of cardiac CT--an impressive growth in
      recent years.

PMID- 25576404
TI  - The effects of baicalin on the TLR2/4 signaling pathway in the peripheral blood
      mononuclear cells of a lipopolysaccharide-induced rat fever model.
AB  - Baicalin, which is a flavonoid compound isolated from Scutellariae radix, has
      significant antipyretic effects. The aim of the present study was to evaluate the
      effects of baicalin on the Toll-like receptor 2/4 (TLR2/4) signaling pathway in
      the peripheral blood mononuclear cells (PBMCs) of a rat fever model induced by
      lipopolysaccharide (LPS). Sprague-Dawley rats were injected intraperitoneally
      with 100MUg/kg LPS with or without a 160mg/kg baicalin treatment to induce fever.
      The results showed that baicalin significantly reduced the body temperatures of
      the fever-induced rats, inhibited the LPS-modulated upregulation of TLR4 mRNA and
      protein expression and TNF-alpha and IL-1beta mRNA expression in the rat PBMCs
      and downregulated nuclear factor-kappaB activation with simultaneous decreases in
      TNF-alpha and IL-1beta protein expression. The LPS and baicalin had no
      significant effect on TLR2 mRNA or protein expression in the PBMCs. These data
      suggest that baicalin can inhibit the TLR4 signaling pathway in the PBMCs of our
      animal model. Our findings may provide new mechanistic insights into the
      antipyretic effects of baicalin. 

PMID- 25576406
TI  - Coronary CT angiography for the detection of coronary artery stenosis in patients
      referred for transcatheter aortic valve replacement.
AB  - BACKGROUND: Coronary CT has become the foremost noninvasive imaging modality for
      detecting coronary stenoses in patients with suspected coronary artery disease.
      Nevertheless, little is known about its performance in patients undergoing
      transcatheter aortic valve replacement (TAVR). OBJECTIVE: This study investigates
      the diagnostic performance of coronary CT angiography in patients referred for
      TAVR. METHODS: One hundred and fifteen consecutive patients with severe aortic
      stenosis underwent CT angiography with retrospective electrocardiography
      triggered acquisition and an iterative reconstruction algorithm, of whom 23 (20%)
      had prior coronary artery bypass graft (CABG) surgery. Diagnostic accuracy of CT
      for detecting significant coronary stenosis (>= 50% luminal diameter stenosis in
      segments >= 2 mm) in the left main, proximal, or middle segments of coronary
      arteries and bypass grafts was compared with that of invasive coronary
      angiography. RESULTS: In the overall study population, the sensitivity,
      specificity, and positive and negative predictive value of CT angiography for the
      detection of coronary segment or bypass graft lesions were 96% (47 of 49), 73%
      (48 of 66), 72% (47 of 65), and 96% (48 of 50), respectively. The per-patient
      diagnostic yield of CT angiography was consistent among patients without prior
      CABG (93% [28 of 30], 73% [45 of 62], 62% [28 of 45], and 96% [45 of 47],
      respectively) and among patients with prior CABG (100% [19 of 19], 75% [3 of 4],
      95% [19 of 20], and 100% [3 of 3], respectively). CONCLUSION: Among patients
      referred for TAVR, coronary CT angiography with retrospective gating and
      iterative reconstruction may allow detection of significant stenosis in the
      proximal or middle segments of coronary arteries and could permit the evaluation
      of patients after bypass grafts.

PMID- 25576409
TI  - [Ebola 2014: drama and hope].

PMID- 25576408
TI  - Natural organic matter alters size-dependent effects of nanoCuO on the feeding
      behaviour of freshwater invertebrate shredders.
AB  - Nanoparticle size and the presence of natural organic matter (NOM) may influence
      the toxicity of nanoCuO to aquatic biota, but their interactive effects have been
      poorly investigated. We examined the feeding behaviour of the invertebrate
      shredder Allogamus ligonifer when exposed to sublethal concentrations of nanoCuO
      (50 and 100 mg L(-1)) with three particle sizes (12, 50 and 80 nm) in the absence
      or presence of humic acid (HA, 100 mg L(-1)) as a proxy of NOM. We further
      examined the ability of invertebrates to recover from the stressors. In the
      absence of nanoCuO and HA, the feeding rate of shredders was 0.416 mg leaf DM mg(
      1 )animal DM day(-1). The exposure to increased nanoCuO concentrations inhibited
      the feeding rate and effects were stronger as nanoparticle size decreased (up to
      83.3% inhibition for 12 nm particles). The exposure to HA alone inhibited the
      feeding activity by 52.7%. However, the co-exposure to nanoCuO and HA alleviated
      the inhibitory effects promoted by smaller and medium sized nanoCuO (up to
      29.5%). The recovery of feeding activity by the shredders after stress removal
      was very low; maximum recovery (16.7%) was found for invertebrates rescued from
      pre-exposure to lower concentration of nanoCuO with larger size.

PMID- 25576410
TI  - Stenotrophomonas maltophilia interferes via the DSF-mediated quorum sensing
      system with Candida albicans filamentation and its planktonic and biofilm modes
      of growth.
AB  - Stenotrophomonas maltophilia is a nosocomial pathogen of increasing importance.
      S. maltophilia K279a genome encodes a diffusible signal factor (DSF) dependent
      quorum sensing (QS) system that was first identified in Xanthomonas campestris
      pv. campestris. DSF from X. campestris is a homologue of farnesoic acid, a
      Candida albicans QS signal which inhibits the yeast-to-hyphal shift. Here we
      describe the antagonistic effects of S. maltophilia on C. albicans on
      filamentation as well as on its planktonic and biofilm modes of growth. To
      determine the role of the DSF-mediated quorum sensing system in these effects, C.
      albicans ATCC 10231 and C. albicans tup1 mutant, locked in the filamentous form,
      were grown with K279a or with its rpfF deletion mutant (DSF-). A significant
      reduction in viable counts of C. albicans was observed in planktonic cocultures
      with K279a as well as in mixed biofilms. Furthermore, no viable cells of C.
      albicans tup1 were recovered from K279a mixed biofilms. Fungal viability was also
      assessed by labeling biofilms with SYTO 9 and propidium iodide. Confocal images
      showed that K279a can kill hyphae and also yeast cells. Light microscopic
      analysis showed that K279a severely affects hyphae integrity. On the other hand,
      the presence of K279a rpfF did not affect fungal morphology or viability. In
      conclusion, we report for the first time that S. maltophilia interferes with two
      key virulence factors of C. albicans, the yeast-to-hyphal transition and biofilm
      formation. DSF could be directly responsible for these effects or may induce the
      gene expression involved in antifungal activity.

PMID- 25576407
TI  - Analysis of ventricular function by CT.
AB  - The assessment of ventricular function, cardiac chamber dimensions, and
      ventricular mass is fundamental for clinical diagnosis, risk assessment,
      therapeutic decisions, and prognosis in patients with cardiac disease. Although
      cardiac CT is a noninvasive imaging technique often used for the assessment of
      coronary artery disease, it can also be used to obtain important data about left
      and right ventricular function and morphology. In this review, we will discuss
      the clinical indications for the use of cardiac CT for ventricular analysis,
      review the evidence on the assessment of ventricular function compared with
      existing imaging modalities such cardiac magnetic resonance imaging and
      echocardiography, provide a typical cardiac CT protocol for image acquisition and
      postprocessing for ventricular analysis, and provide step-by-step instructions to
      acquire multiplanar cardiac views for ventricular assessment from the standard
      axial, coronal, and sagittal planes. Furthermore, both qualitative and
      quantitative assessments of ventricular function as well as sample reporting are
      detailed. 

PMID- 25576412
TI  - First isolation of enteroaggregative Escherichia coli O104:H4 from a diarrhea
      case in Argentina.
AB  - We describe the first isolation of an enteroaggregative Escherichia coli (EAEC)
      O104:H4 strain associated with an acute diarrhea case in Argentina. Two multiplex
      PCRs (mPCR) were performed as screening of genes mPCR1 (eae, lt, and st) and
      mPCR2 (IpaH, aggR, stx1 and stx2). A mPCR to detect the rfbO104, fliCH4 and terD
      genes, and PCR assays for the detection of pCVD432 plasmid, aaiC and lpfO113
      genes were included. Biochemical and antimicrobial susceptibility assays as well
      as serotyping were performed. The identified E. coli strain was susceptible to
      all antimicrobials tested and harbored the aggR, aaiC, pCVD432 plasmid, lpfO113,
      rfbO104, fliCH4 and terD genes. Although serotype EAEC O104:H4 rarely spreads and
      sporadic cases have been reported, global concern increased after the large-scale
      outbreak in Europe in 2011. The finding of EAEC O104:H4 reinforces the need for
      improved methodologies for the detection of all E. coli pathotypes. 

PMID- 25576411
TI  - [Brain abscess caused by Haemophilus influenzae type E in a pediatric patient
      suffering from Apert syndrome].
AB  - We report a case of a brain abscess caused by Haemophilus influenzae type e in a
      12 year-old patient suffering from Apert syndrome. Apert syndrome is
      characterized by the premature closure of cranial sutures. In 2010 the patient
      suffered head trauma in the frontal area with cranial fracture and a
      cerebrospinal fluid fistula. In February 2013 he was admitted to hospital with
      fever, vomiting and generalized tonic-clonic seizure with deteriorating mental
      status/progressive sensory impairment. The computerized axial tomographic scan
      showed a right frontal lesion, perilesional edema, mild ventricular dilatation
      and pansinusitis. A brain abscess was diagnosed and drained. The clinical sample
      was then cultured. A gram negative coccobacillus was isolated and identified as
      Haemophilus influenzae serotype e. Empirical treatment was started with meropenem
      (120 mg/kg/day) and vancomycin (60 mg/kg/day), which was later switched to
      ceftriaxone (100 mg/kg/day) and metronidazole (500 mg/8 h) after culture results
      arrived. The patient was discharged in good clinical condition.

PMID- 25576413
TI  - [Molecular identification of Candida lusitaniae in lower respiratory tract
      infection].
AB  - Candida lusitaniae is a yeast that has emerged as a low frequency nosocomial
      pathogen in deep infections. Although it usually shows in vitro susceptibility to
      all antifungal agents, in vivo resistance to amphotericin B has been observed in
      several clinical cases. Therefore, its early identification in the course of
      therapy is important. We report the isolation of C. lusitaniae as an etiologic
      agent of a lower respiratory tract infection in a male patient. Urine and sputum
      cultures were negative for bacteria and positive for this yeast. Isolates were
      identified by routine phenotypic methods and confirmed by sequencing and
      restriction fragment length polymorphism analysis of PCR internal spacer of
      ribosomal DNA. 

PMID- 25576414
TI  - [Isolation of Sporothrix pallida complex in clinical and environmental samples
      from Chile].
AB  - The isolation of S. pallida complex from medical samples and home garden soil of
      a patient in Chile is here in reported. Fungi of the Sporothrix schenckii complex
      can cause various infections. In Chile, the medical and environmental isolates of
      these this complex are rare. The aim of this study was to identify an unusual
      agent in a case of onychomycosis and to detect its presence in the patient's home
      garden. For this purpose, clinical samples were obtained by scraping the
      patient's subungueal first right toe nail as well as by taking soil samples from
      different areas of her home garden. Species identification was performed by
      morphophysiology and one of the strains isolated from the patient's toe nail was
      sent to CBS for molecular confirmation (14.062). S. pallida complex was
      identified both from the patient's toe nail and samples taken from her home
      garden. 

PMID- 25576415
TI  - [Endemic and epidemic bovine neosporosis: description of two events in beef
      cattle].
AB  - The aim of this study was to describe two events in which Neospora caninum was
      involved in bovine abortions in beef cattle. In the first event, 11 abortions in
      57 heifers were recorded in 45 days. One aborted heifer was 5 times more likely
      to be seropositive than a non-aborted heifer (OR=4.9; IC 1.2-19.9) (p<0.05). In
      the second event, no association between serological results and abortions were
      observed (OR=0,69; 0,06-7,31) (p>0.05). Neither antibodies nor isolation of other
      pathogens were achieved in any case. On the contrary, antibodies and
      pathognomonic histopathological lesions were observed in the four fetuses from
      both cases. Interestingly, the findings in the first event suggest the epidemic
      behavior of the disease. In contrast, in the second event it appears that few
      abortions were due to N. caninum, suggesting the presence of endemic neosporosis.

PMID- 25576416
TI  - [Frequency and antimicrobial resistance of Acinetobacter species in a university
      hospital of Buenos Aires City].
AB  - Two-hundred Acinetobacter isolates belonging to 200 patients admitted to Hospital
      de Clinicas Jose de San Martin during the period March 2013-June 2014 were
      analyzed. The identification was performed by mass spectrometry and was confirmed
      by molecular methods. Susceptibility to antimicrobials was studied by the Vitek-2
      system. A 94% correlation of both identification methods was found. Multidrug
      resistant Acinetobacter baumannii was the predominant genomic species (92.6%) in
      hospital-acquired infections, whereas Acinetobacter pitti and Acinetobacter
      nosocomialis accounted for 3.5% and 0.5% of the isolates recovered, respectively.
      In community-acquired infections a major predominance of the different genomic
      species was observed. Acinetobacter johnsonii and A. baumannii are the most
      frequent species, accounting for 45.9% of the isolates recovered. Resistance to
      carbapenems and minocycline was only observed in A. baumannii. Mass
      spectrophotometry was an effective tool for the identification of the different
      genomic species. 

PMID- 25576417
TI  - Microbiological and physicochemical analysis of yatei (Tetragonisca angustula)
      honey for assessing quality standards and commercialization.
AB  - Due to the interest in the production and trading of yatei (Tetragonisca
      angustula) honey in the province of Misiones, Argentina, in this work we assessed
      microbiological and physicochemical parameters in order to contribute to the
      elaboration of standards for quality control and promote commercialization.
      Results showed that yatei honey samples had significantly different
      microbiological and physicochemical characteristics in comparison to established
      quality standards for Apis mellifera honey. Thus, we observed that values for pH
      (3.72), glucose (19.01 g/100g) and fructose (23.74 g/100g) were lower than A.
      mellifera quality standards, while acidity (79.42 meq/kg), moisture (24%), and
      mould and yeast count (MY) (3.02 log CFU/g) were higher. The acid content was
      correlated with glucose (R2=0.75) and fructose (R2=0.68) content, and also with
      mould and yeast counts (R2=0.45) to a lesser extent. The incidence of
      microorganisms in yatei honey samples reached 42.85% and 39% for Clostridium
      sulfite-reducers and Bacillus spp., respectively. No C. botulinum or B. cereus
      cells were detected. Enterococcus spp. and Staphylococcus spp. incidence was
      similar (ca. 7.14%), whereas Escherichia coli and Salmonella spp. were not
      detected. We conclude that the microbiological and physicochemical properties of
      yatei honey are different from those of A. mellifera honey; hence, different
      quality standards could be implemented to promote its commercialization.

PMID- 25576418
TI  - Bacteriophage cocktail reduces Salmonella enterica serovar Enteritidis counts in
      raw and smoked salmon tissues.
AB  - The use of bacteriophages for the biocontrol of food-borne pathogens is
      increasingly gaining acceptance. In this study, the effectiveness of
      bacteriophages to reduce Salmonella Enteritidis counts was evaluated in raw and
      smoked salmon tissues. Groups of 25 samples each were contaminated with S.
      Enteritidis, treated with a phage mix and then incubated for ten days at 18 
      degrees C and 4  degrees C. A significant bacterial reduction was obtained on
      days 3, 6 and 10 in raw salmon samples incubated at 18  degrees C (from 0.75 to
      3.19 log10 CFU/g) and at 4  degrees C (from 2.82 to 3.12 log10 CFU/g), whereas in
      smoked salmon lower reductions were achieved (from 1.02 to 1.96 log10 CFU/g at 18
      degrees C and from 0.50 to 1.16 log10 CFU/g at 4  degrees C). These results show
      the potential effectiveness of this bacteriophage cocktail as a biocontrol agent
      against S. Enteritidis in raw and smoked salmon tissues.

PMID- 25576420
TI  - Response of ligninolytic macrofungi to the herbicide atrazine: dose-response
      bioassays.
AB  - The effect of atrazine concentrations on mycelial growth and ligninolytic enzyme
      activities of eight native ligninolytic macrofungi isolated in Veracruz, Mexico,
      were evaluated in a semi-solid culture medium. Inhibition of mycelial growth and
      growth rates were significantly affected (p=0.05) by atrazine concentrations
      (468, 937, 1875, and 3750 mg/l). In accordance with the median effective
      concentration (EC50), Pleurotus sp. strain 1 proved to be the most tolerant
      isolate to atrazine (EC50=2281.0 mg/l), although its enzyme activity was not the
      highest. Pycnoporus sanguineus strain 2, Daedalea elegans and Trametes maxima
      showed high laccase activity (62.7, 31.9, 29.3 U mg/protein, respectively)
      without atrazine (control); however, this activity significantly increased
      (p<0.05) (to 191.1, 83.5 and 120.6 U mg/protein, respectively) owing to the
      effect of atrazine (937 mg/l) in the culture medium. Pleurotus sp. strain 2 and
      Cymatoderma elegans significantly increased (p<0.05) their manganese peroxidase
      (MnP) activities under atrazine stress at 468 mg/l. The isolates with high EC50
      (Pleurotus sp. strain 1) and high enzymatic activity (P. sanguineus strain 2 and
      T. maxima) could be considered for future studies on atrazine mycodegradation.
      Furthermore, this study confirms that atrazine can increase laccase and MnP
      activities in ligninolytic macrofungi.

PMID- 25576419
TI  - [Characterization of growth-promoting rhizobacteria in Eucalyptus nitens
      seedlings].
AB  - Rhizospheric and endophytic bacteria were isolated from the rizosphere and root
      tissue of Eucalyptus nitens. The objective of this work was to evaluate their
      capacity to promote growth in seedlings of the same species under greenhouse
      conditions. The isolates that improved seedling growth were identified and
      characterized by their capacity to produce indoleacetic acid (IAA), solubilize
      phosphates and increase 1-aminocyclopropane-1-carboxylate (ACC) deaminase
      activity. One hundred and five morphologically different strains were isolated,
      15 of which promoted E. nitens seedling growth, significantly increasing the
      height (50%), root length (45%) as well as the aerial and root dry weight (142%
      and 135% respectively) of the plants. Bacteria belonged to the genus
      Arthrobacter, Lysinibacillus, Rahnella and Bacillus. Isolates A.
      phenanthrenivorans 21 and B. cereus 113 improved 3.15 times the emergence of E.
      nitens after 12 days, compared to control samples. Among isolated R. aquatilis,
      78 showed the highest production of IAA (97.5+/-2.87 MUg/ml) in the presence of
      tryptophan and the highest solubilizer index (2.4) for phosphorus, while B.
      amyloliquefaciens 60 isolate was positive for ACC deaminase activity. Our results
      reveal the potential of the studied rhizobacteria as promoters of emergence and
      seedling growth of E. nitens, and their possible use as PGPR inoculants, since
      they have more than one mechanism associated with plant growth promotion.

PMID- 25576421
TI  - Diurnal variation in bacterioplankton composition and DNA damage in the microbial
      community from an Andean oligotrophic lake.
AB  - Laguna Azul is an oligotrophic lake situated at 4,560 m above sea level and
      subject to a high level of solar radiation. Bacterioplankton community
      composition (BCC) was analysed by denaturing gradient gel electrophoresis and the
      impact of solar ultraviolet radiation was assessed by measuring cyclobutane
      pyrimidine dimers (CPD). Furthermore, pure cultures of Acinetobacter johnsonii A2
      and Rhodococcus sp. A5 were exposed simultaneously and CPD accumulation was
      studied. Gel analyses generated a total of 7 sequences belonging to Alpha
      proteobacteria (1 band), Beta-proteobacteria (1 band), Bacteroidetes (2 bands),
      Actinobacteria (1 band), and Firmicutes (1 band). DGGE profiles showed minimal
      changes in BCC and no CPD was detected even though a high level of damage was
      found in biodosimeters. A. johnsonii A2 showed low level of DNA damage while
      Rhodococcus sp. A5 exhibited high resistance since no CPD were detected under
      natural UV-B exposure, suggesting that the bacterial community is well adapted to
      this highly solar irradiated environment.

PMID- 25576422
TI  - [Aspects of the innate immune response to intramammary Staphylococcus aureus
      infections in cattle].
AB  - Staphylococcus aureus is the pathogen most frequently isolated from bovine
      mastitis worldwide, causing chronic intramammary infections that limit profitable
      dairying. The objective of this article is to characterize the mechanisms
      involved in S. aureus mammary gland infections considering two different aspects
      of the infectious process; on the one hand, the aspects involved in the host
      innate immune response and on the other hand, the capacity of this organism to
      evade the immune system and interact with different cell types. The exploration
      of S. aureus interactions with the immune response of bovine mammary gland will
      help identify targets to outline new preventive or curative alternatives for
      intramammary infections caused by this organism.

PMID- 25576423
TI  - Fungi and bacteria in the biodeterioration of archeological fibers. Analysis
      using different microscopic techniques.

PMID- 25576424
TI  - [Trypanosoma cruzi in an immunocompromised patient. Reactivation of Chagas
      disease in a resident of La Rioja city, Argentina].

PMID- 25576425
TI  - Generation of highly cytotoxic natural killer cells for treatment of acute
      myelogenous leukemia using a feeder-free, particle-based approach.
AB  - Natural killer (NK) cell immunotherapy as a cancer treatment shows promise, but
      expanding NK cells consistently from a small fraction (~ 5%) of peripheral blood
      mononuclear cells (PBMCs) to therapeutic amounts remains challenging. Most
      current ex vivo expansion methods use co-culture with feeder cells (FC), but
      their use poses challenges for wide clinical application. We developed a particle
      based NK cell expansion technology that uses plasma membrane particles (PM
      particles) derived from K562-mbIL15-41BBL FCs. These PM-particles induce
      selective expansion of NK cells from unsorted PBMCs, with NK cells increasing 250
      fold (median, 35; 10 donors; range, 94 to 1492) after 14 days of culture and up
      to 1265-fold (n = 14; range, 280 to 4426) typically after 17 days. The rate and
      efficiency of NK cell expansions with PM-particles and live FCs are comparable
      and far better than stimulation with soluble 41BBL, IL-15, and IL-2. Furthermore,
      NK cells expand selectively with PM-particles to 86% (median, 35; range, 71% to
      99%) of total cells after 14 days. The extent of NK cell expansion and cell
      content was PM-particle concentration dependent. These NK cells were highly
      cytotoxic against several leukemic cell lines and also against patient acute
      myelogenous leukemia blasts. Phenotype analysis of these PM-particle-expanded NK
      cells was consistent with an activated cytotoxic phenotype. This novel NK cell
      expansion methodology has promising clinical therapeutic implications.

PMID- 25576427
TI  - Guest-editorial: Computer-based intelligent technologies for improving the
      quality of life.

PMID- 25576426
TI  - Bridging the gap in connectomic studies: A particle filtering framework for
      estimating structural connectivity at network scale.
AB  - The ultimate goal of neuroscience is understanding the brain at a functional
      level. This requires the investigation of the structural connectivity at multiple
      scales: from the single-neuron micro-connectomics to the brain-region macro
      connectomics. In this work, we address the study of connectomics at the
      intermediate mesoscale, introducing a probabilistic approach capable of
      reconstructing complex topologies of large neuronal networks. Suitable
      directional features are designed to model the local neuritic architecture and a
      feature-based particle filtering framework is proposed which allows the spatial
      tracking of neurites on microscopy images. The experimental results on cultures
      of increasing complexity, grown on High-Density Micro Electrode Arrays, show good
      stability and performance as compared to ground truth annotations drawn by domain
      experts. We also show how the method can be used to dissect the structural
      connectivity of inhibitory and excitatory subnetworks opening new perspectives
      towards the investigation of functional interactions among multiple cellular
      populations. 

PMID- 25576428
TI  - Accentuated hypo- and hyper-NK lymphocyte CD8 expression is a marker of NK
      subsets' misbalance and is predictive for reproductive failures.
AB  - INTRODUCTION: NK cells play critical yet poorly defined role in reproductive
      processes. Role of CD8alphaalpha expression on a part of peripheral blood NK
      lymphocyte population is not clear. PATIENTS AND METHODS: During isolated double
      blinded clinical investigation we studied blood samples from 153 women with
      multiple reproductive failures undergoing IVF which were drawn 5-12d before
      embryo transfer procedure. 90 women had IVF failures (IVFf), 24 became pregnant
      with subsequent pregnancy failure (Pf), 39 became pregnant with subsequent
      successful pregnancy. During retrospective study we analyzed our laboratory data
      of 1045 infertile women which underwent routine immunology investigation after
      IVF failures. Lymphocyte phenotype and NK cytotoxicity was studied by FACScan
      flow cytometer using BD monoclonal abs. RESULTS: We showed that NK-CD8 expression
      being increased? (>60%) was predictive for IVFf (OR 3.523, p=0.0193, n=23) while
      being decreased? (<40%) was significantly predictive for subsequent Pf (OR 4.571,
      p=0.0418, n=37). Balanced "conditionally normal" NKCD8 expression (40-60%, n=93)
      was very significantly predictive for whole reproductive success after IVF (OR
      3.972, p=0.0021). Analysing retrospective data, we found decreased CD3- CD56++
      and T lymphocyte frequency in both "accentuated" groups compared to patients with
      "conditionally normal" NK-CD8 expression (n=562). NK-CD8 expression? (n=341) was
      associated with elevated HLADR expression on NK, CD3+, CD3+ CD8+, CD3+ CD4+
      cells. Meanwhile, NK-CD8 expression ? (n=142) was associated with elevated NK
      frequency, NK cytotoxicity levels and CD158a expression on NK cells,
      simultaneously with decreased CD3CD8 and CD3+ CD56+ numbers. CONCLUSION: Both
      hypo- and hyper-NK lymphocyte CD8 expression "accentuations" associated with NK
      subsets' misbalance (NK and T lymphocyte phenotype and cytotoxicity). Both hypo-
      and hyper-NK lymphocyte CD8 expression "accentuations" associated with poor IVF
      outcome, possibly through their association with other unfavorable accentuated
      parameters that result into unfavorable combination of "accentuated phenotype".

PMID- 25576429
TI  - Risk factors for piperacillin/tazobactam-resistant Gram-negative infection in
      hematology/oncology patients with febrile neutropenia.
AB  - PURPOSE: Febrile neutropenia (FN) is a life-threatening complication of cancer
      therapy, and initial ineffective therapy is associated with poor outcomes.
      Piperacillin/tazobactam (PTZ) is a commonly used empiric antibiotic for the
      treatment of FN, but resistance among Gram-negative pathogens is well described.
      We conducted a retrospective case-control study to identify risk factors for PTZ
      resistant (PTZ-R) Gram-negative isolates. METHODS: Hematology/oncology patients
      with FN from November 2007 to November 2013 with a positive culture for Gram
      negative bacilli were divided into two groups: PTZ-sensitive (PTZ-S) and PTZ-R. A
      multivariable model using logistic regression was constructed to identify risk
      factors for PTZ-R. RESULTS: A total of 171 patients were included (25 PTZ-R, 146
      PTZ-S), yielding a 14.6 % resistance rate. Thirty-day all-cause mortality was
      significantly higher in the PTZ-R group (29 vs 11 %, P = 0.024). Multivariable
      analysis yielded intensive care unit (ICU) status (odds ratio (OR) 20.18; 95 %
      confidence interval (CI) 1.03-397.35; P = 0.048), antibiotics for > 14 days in
      the previous 90 days (OR 6.02; CI 1.17-30.93; P = 0.032), and respiratory source
      (OR 13.65; CI 1.14-163.57; P = 0.039) as significant risk factors for PTZ-R, and
      the receiver operating characteristic area under the curve of the model was
      0.894. Among PTZ-R isolates, 88 % were sensitive to meropenem and 100 % were
      sensitive to amikacin. CONCLUSIONS: Given the high mortality rates in the PTZ-R
      group, a risk-factor-guided approach driven by this multivariable model may help
      identify patients that could benefit from amikacin combination therapy to help
      optimize empiric therapy in this setting.

PMID- 25576431
TI  - Decision-making preferences of Jordanian women diagnosed with breast cancer.
AB  - PURPOSE: The purpose of the study was to determine Jordanian women's preferences
      regarding participation in decision-making related to their breast cancer
      treatment. METHODS: A cross-sectional survey design was used in this study. A
      convenience sample of 156 Jordanian women, who had a confirmed, first-time
      diagnosis of breast cancer within 18 months prior to the study and had undergone
      treatment at three hospitals in Central and Northern Jordan, was recruited for
      the study. A modified version of the Control Preferences Scale was used for data
      collection. RESULTS: More than half of the participants (57 %) wanted the
      physician to make the decision about the appropriate treatment, approximately 33
      % wanted to share the decision with the physician, and only 10 % wanted to make
      their own decisions. Participants aged more than 50 years, those with secondary
      school education or less, and those who were undergoing treatment at the public
      or teaching hospital under study were more likely to prefer a passive role in
      decision-making regarding treatment. CONCLUSIONS: Although more than half of the
      participants involved in this study preferred to play a passive role, their
      preferences in this regard varied. This highlighted the importance of
      individually assessing patients' preferences regarding participation in the
      decision-making process and provision of information that is tailored according
      to each patient's needs.

PMID- 25576430
TI  - Analysis of factors related to arm weakness in patients with breast cancer
      related lymphedema.
AB  - PURPOSE: The aim of this study was to evaluate the ratio of significant weakness
      in the affected arm of breast cancer-related lymphedema patients to their
      unaffected side. Another purpose was to identify factors related to arm weakness
      and physical function in patients with breast cancer-related lymphedema. METHODS:
      Consecutive patients (n = 80) attended a single evaluation session following
      their outpatient lymphedema clinic visit. Possible independent factors (i.e.,
      lymphedema, pain, psychological, educational, and behavioral) were evaluated.
      Handgrip strength was used to assess upper extremity muscle strength and the
      disabilities of arm, shoulder, and hand (DASH) questionnaire was used to assess
      upper extremity physical function. Multivariate logistic regression was performed
      using factors that had significant differences between the handgrip weakness and
      non-weakness groups. RESULTS: Out of the 80 patients with breast cancer-related
      lymphedema, 29 patients (36.3 %) had significant weakness in the affected arm.
      Weakness of the arm with lymphedema was not related to lymphedema itself, but was
      related to the fear of using the affected limb (odds ratio = 1.76, 95 %
      confidence interval = 1.30-2.37). Fears of using the affected limb and depression
      significantly contributed to the variance in DASH scores. CONCLUSIONS:
      Appropriate physical and psychological interventions, including providing
      accurate information and reassurance of physical activity safety, are necessary
      to prevent arm weakness and physical dysfunction in patients with breast cancer
      related lymphedema.

PMID- 25576432
TI  - Successful use of central venous catheters in the management of recurrent
      malignant pleural effusions: one new option.
AB  - BACKGROUND: Malignant pleural effusion (MPE) is a common clinical problem in
      patients with malignancy. To date, placement of various catheters has been
      suggested as an effective alternative method for traditional treatment of
      recurrent MPE. In this study, we report our experience in managing treatment of
      recurrent MPE by placing a central vein catheter without a radiologic guide.
      METHODS: Patients with recurrent MPE who underwent triple-lumen central vein
      catheter insertion (2010-2013) were retrospectively reviewed. Clinical,
      procedural, complication, and outcome details were analyzed. Patients were
      carefully selected, and the central catheters were inserted as a palliative
      measure. We assessed the quality of life of patients using the EORTC QLQ-C30.
      RESULTS: A total of 84 patients with recurrent MPE were enrolled in this study.
      Fifty-six males and 28 females with mean age of 57.8 +/- 12.4 years old underwent
      the procedure. There were no preoperative or postoperative complications related
      to the procedure. The EORTC QLQ-C30 questionnaire showed a significant
      improvement following catheter placement in symptom scales at 30 days (p = 0.01)
      and at 60 days (p = 0.002). CONCLUSIONS: Triple-lumen central catheter insertion
      is a simple, noninvasive option in patients with recurrent MPE that can be
      performed the patient's bedside. Further research is needed to confirm the
      results and to assess the impact of central catheter insertion on the quality of
      life of these patients.

PMID- 25576433
TI  - Phase III placebo-controlled, double-blind, randomized trial of pegfilgrastim to
      reduce the risk of febrile neutropenia in breast cancer patients receiving
      docetaxel/cyclophosphamide chemotherapy.
AB  - PURPOSE: Pegfilgrastim is a pegylated form of filgrastim, a recombinant protein
      of granulocyte colony-stimulating factor, that is used to reduce the risk of
      febrile neutropenia (FN). Here, we report the results of a phase III trial of
      pegfilgrastim in breast cancer patients receiving docetaxel and cyclophosphamide
      (TC) chemotherapy. METHODS: We conducted a double-blind, placebo-controlled,
      randomized trial to determine the efficacy of pegfilgrastim in reducing the risk
      of FN in early-stage breast cancer patients. A total of 351 women (177 in the
      pegfilgrastim group and 174 in the placebo group) between 20 and 69 years of age
      with stage I-III invasive breast carcinoma who were to receive TC chemotherapy
      (docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks) as either
      neoadjuvant or adjuvant therapy were enrolled; 346 of these patients were treated
      with either pegfilgrastim (n = 173) or placebo (n = 173). RESULTS: The incidence
      of FN was significantly lower in the pegfilgrastim group than in the placebo
      group (1.2 vs. 68.8 %, respectively; P < 0.001). In addition, patients in the
      pegfilgrastim group required less hospitalization and antibiotics for FN. Most
      adverse events were consistent with those expected for breast cancer subjects
      receiving TC chemotherapy. CONCLUSIONS: Pegfilgrastim is safe and significantly
      reduces the incidence of FN in breast cancer patients.

PMID- 25576434
TI  - Geriatric assessment as an aide to understanding falls in older adults with
      cancer.
AB  - PURPOSE: In older adults, falls are a common cause of functional decline,
      institutionalization, and reduced quality of life. This study (1) investigates
      the prevalence of falls in a large sample of community-dwelling older adults with
      a cancer diagnosis and (2) evaluates the association of falls with domains of
      comprehensive geriatric assessment (CGA) that pertain to falls risk. METHODS:
      Patients completed a CGA that includes a self-reported measure of number of falls
      in the past 6 months. Summary statistics are used to describe prevalence of falls
      and associations with hypothesized risk factors using Fisher's exact tests and
      multivariable logistic regression. RESULTS: A total of 1172 patients were
      enrolled, mean age 73 (65-99), 74 % female, and 89 % Caucasian. Two hundred fifty
      six (22 %) reported one or more falls within the last 6 months. Patients with at
      least one instrumental activities of daily living (IADL) or physical function
      deficit had more falls as compared those with no deficits identified (p <=
      0.001). The number of daily medications, comorbidities, Timed Up and Go score >14
      s, and poor vision were also associated with increased falls (p <= 0.001).
      Reduced physical function, poor vision, and low performance status had the
      highest adjusted odds ratio (3.6, 3.4, and 3.0, respectively) for falls.
      CONCLUSIONS: There is a high prevalence of falls in community-dwelling older
      patients with a cancer diagnosis. Falls are significantly associated with several
      measures of geriatric assessment including IADL, physical function,
      comorbidities, medications, and vision. Timely identification and management of
      risk factors for falls are important considerations in the care of older cancer
      patients.

PMID- 25576435
TI  - Movement of chromosomes with severed kinetochore microtubules.
AB  - Experiments dating from 1966 and thereafter showed that anaphase chromosomes
      continued to move poleward after their kinetochore microtubules were severed by
      ultraviolet microbeam irradiation. These observations were initially met with
      scepticism as they contradicted the prevailing view that kinetochore fibre
      microtubules pulled chromosomes to the pole. However, recent experiments using
      visible light laser microbeam irradiations have corroborated these earlier
      experiments as anaphase chromosomes again were shown to move poleward after their
      kinetochore microtubules were severed. Thus, multiple independent studies using
      different techniques have shown that chromosomes can indeed move poleward without
      direct microtubule connections to the pole, with only a kinetochore 'stub' of
      microtubules. An issue not yet settled is: what propels the disconnected
      chromosome? There are two not necessarily mutually exclusive proposals in the
      literature: (1) chromosome movement is propelled by the kinetochore stub
      interacting with non-kinetochore microtubules and (2) chromosome movement is
      propelled by a spindle matrix acting on the stub. In this review, we summarise
      the data indicating that chromosomes can move with severed kinetochore
      microtubules and we discuss proposed mechanisms for chromosome movement with
      severed kinetochore microtubules.

PMID- 25576436
TI  - [Good reproducibility of a 14-item food frequency questionnaire for
      cardiovascular prevention in students].
AB  - Diet is a modifiable risk factor of atherosclerosis. A 14-item food frequency
      questionnaire (FFQ) has been developed. The reproducibility of this FFQ is
      unknown in a student population whereas its use could be of interest. METHODS:
      This FFQ allows calculating different scores for different food groups involved
      in cardiovascular disease. The vascular dietary score (VDS) can be calculated.
      The VSD ranges from -17 to +19. The higher the VSD, the better diet.
      Reproducibility was assessed in sports faculty students using mean tests
      comparing measurement 1 and 2 (minimum time interval >= 7 days) and intra-class
      correlation (ICC) tests. RESULTS: Thirty students (50% men) were included in a
      French Sports Faculty. Time between two FFQ assessments was 19 +/- 9 days. Mean
      VSD was 0.50 +/- 3.70 for the first assessment and 0.30 +/- 3.14 for the second
      one (non significant). Any score for each food group was statistically
      significant between the first and the second measurement. ICC of VSD was 0.68
      [95% confidence interval: 0.43-0.83]. CONCLUSION: This FFQ that assesses a risky
      vascular diet has good reproducibility. This tool could be useful for large
      studies involving students.

PMID- 25576437
TI  - Zirconia abutments and restorations: from laboratory to clinical investigations.
AB  - In last years the use of zirconia in dentistry has become very popular.
      Unfortunately, the clinical indications for a dental use of zirconia are not
      completely clear yet, neither are their limitations. The objective of this review
      was to evaluate the basic science knowledge on zirconia and to discuss some
      aspects of the clinical behavior of zirconia-based restorations. In particular,
      one of the goals was highlighting the possible correlation between in vitro and
      in vivo studies. The definition of concepts like success, survival and failure
      was still debated and the correlation between in vitro results and predictability
      of clinical behavior was investigated. 

PMID- 25576438
TI  - High cumulative oxygen levels are associated with improved survival of children
      treated with mild therapeutic hypothermia after cardiac arrest.
AB  - AIM: The aim of this study was to analyze the relationship between the partial
      pressure of arterial oxygen (PaO2) and in-hospital (IH) mortality in children
      after cardiac arrest (CA) using the conventional cutoff analysis, which was
      compared with the cumulative analysis, a new method in PaO2 analysis.
      Additionally, we analyzed this relationship for children with and without mild
      therapeutic hypothermia (MTH; 32-34  degrees C). METHODS: This observational
      cohort study included all children (aged >28 days) with CA and return of
      spontaneous circulation (ROSC) between 2002 and 2011. The first research question
      was the association between PaO2 and IH mortality after ROSC. This was analyzed
      for three hyperoxia cutoff values, and for three time intervals using the
      cumulative PaO2 determined with the area under the curve (AUC). For the second
      research question, these analyses were repeated for children with and without
      MTH. RESULTS: Of the 200 patients included (median age 2.6 years), 84 (42%)
      survived to hospital discharge. Fifty-eight children (29%) were treated with MTH.
      With the cutoff analysis and the AUC analysis we found no relationship between
      PaO2 and IH mortality. However, analysis of the MTH-group showed a lower IH
      mortality in children with high cumulative PaO2 levels on two of the three time
      intervals. Multivariable analysis showed significantly higher odds of survival
      (0.643 (95% confidence interval (CI) 0.424-0.976), 0.554 (95% CI 0.335-0.916)).
      CONCLUSIONS: Cumulative PaO2 analysis showed that the IH mortality is
      significantly lower in MTH-treated children with high PaO2 levels. The effects of
      cumulative PaO2 on the outcome need to be studied further, and this will help us
      to achieve individualized goal-directed therapy.

PMID- 25576439
TI  - Immune and inflammatory responses in pigs infected with Trichuris suis and
      Oesophagostomum dentatum.
AB  - The aim of the present study was to investigate parasite induced immune responses
      in pigs co-infected with Trichuris suis and Oesophagostomum dentatum as compared
      to mono-species infected pigs. T. suis is known to elicit a strong immune
      response leading to rapid expulsion, and a strong antagonistic effect on O.
      dentatum populations has been observed in co-infected pigs. Forty-eight helminth
      naive pigs were allocated into 4 groups in a 2-factorial design. Two groups were
      trickle inoculated with either 10 T. suis eggs/kg/day (Group T) or 20 O. dentatum
      L3/kg/day (Group O). Group OT was infected with same levels of both T. suis and
      O. dentatum (Group OT) and Group C remained uninfected. In each group, six pigs
      were necropsied after 35 days and the remaining pigs after 71 days. Parasite E/S
      antigen specific serum antibodies were quantified by an in-direct ELISA. qPCR was
      used to measure the expression of immune function related genes in the mucosa of
      proximal colon and the draining lymph node. Highly significant interactions were
      identified for O. dentatum specific IgG1 (p<0.0001) and IgG2 (p<0.0006)
      antibodies with a remarkable 2-fold higher antibody response in group OT pigs as
      compared to group O. These findings indicated that T. suis enhanced the antibody
      response against O. dentatum in Group OT. The gene expression data confirmed a
      strong Type 2 response to T. suis (e.g. marked increase in IL-13, ARG1 and CCL11)
      and clearly weaker in amplitude and/or delayed onset response to O. dentatum in
      the single infected group. Interactions were found between the two nematodes with
      regard to several cytokines, e.g. the increase in IL-13 observed in Group T was
      absent in Group OT (p=0.06, proximal colon mucosa, 35 and 71 p.i.). Some of these
      immune response-related interactions may support, or even partially explain, the
      observed interactions between the two worm populations in co-infected pigs.

PMID- 25576441
TI  - Susceptibility of Rhipicephalus (Boophilus) microplus to ivermectin (200, 500 and
      630 MUg/kg) in field studies in Brazil.
AB  - The present study aimed to determine the susceptibility of 17 Rhipicephalus
      (Boophilus) microplus populations, originating in the Southeast and Southern
      regions of Brazil, to different ivermectin concentrations (200, 500 and 630
      MUg/kg), administered through subcutaneous or topical (pour-on) routes. R. (B.)
      microplus populations from the states of Minas Gerais (seven populations), Sao
      Paulo (seven populations) and Parana (three populations) were chosen for the
      tests. The selected cattle were allocated to treatment groups on day 0, and block
      formation was based on the arithmetic mean of female ticks (4.5-8.0 mm long)
      counted on three consecutive days (-3, -2 and -1). To evaluate the therapeutic
      and residual efficacies of these formulations, tick counts (females ranging from
      4.5 to 8.0 mm long) were performed on days 3, 7 and 14 post-treatment, and
      continued on a weekly basis thereafter until the end of each experiment. The
      results obtained throughout this study, utilizing field efficacy studies, allowed
      us to conclude that the resistance of R. (B.) microplus against 200 and 500
      MUg/kg ivermectin is widely disseminated because all tick populations that had
      contact with these specific concentrations were diagnosed as resistant. However,
      it is possible to infer that R. (B.) microplus resistance against 630 MUg/kg
      ivermectin was also widespread, diagnosed at six of ten analyzed properties.
      Resistance of these ectoparasites to 630 MUg/kg ivermectin is most likely
      emerging in three other populations of R. (B.) microplus. Strategies of
      resistance management need to be quickly determined to keep the selection
      pressure at a minimum level in Brazil.

PMID- 25576440
TI  - Pyrantel resistance in two herds of donkey in the UK.
AB  - Resistance to currently available anthelmintics is a serious phenomenon which is
      prevalent globally. Cyathostomins are one of the major parasites, and are of
      primary concern in donkeys. There have been reports of emerging resistance to
      pyrantel, but the status of pyrantel resistance in donkey populations in the UK
      is largely unknown. This report investigates pyrantel resistance in two
      geographically isolated donkey herds in the South West of England. The first herd
      had suspected pyrantel resistance, with already established resistance to other
      anthelmintics. In the second herd the efficacy of pyrantel was not suspected at
      the time the study took place. Faecal Egg Count Reduction Test (FECRT) was
      carried out, revealing large scale resistance. Eighty one percent of the first
      herd and 73% of the second herd had a FEC of less than 95% after treatment, and
      anthelmintic resistance was confirmed using the World Association for the
      Advancement of Veterinary Parasitology guidelines. These findings indicate that
      anthelmintic resistance to pyrantel exists in both tested donkey populations and
      illustrate the continuing development of resistance through different classes of
      chemotherapeutics. 

PMID- 25576442
TI  - Histomonas meleagridis--new insights into an old pathogen.
AB  - The protozoan flagellate Histomonas meleagridis is the etiological agent of
      histomonosis, first described in 1893. It is a fastidious disease in turkeys,
      with pathological lesions in the caeca and liver, sometimes with high mortality.
      In chickens the disease is less fatal and lesions are often confined to the
      caeca. The disease was well controlled by applying nitroimidazoles and
      nitrofurans for therapy or prophylaxis. Since their introduction into the market
      in the middle of the previous century, research nearly ceased as outbreaks of
      histomonosis occurred only very rarely. With the ban of these drugs in the last
      two decades in North America, the European Union and elsewhere, in combination
      with the changes in animal husbandry, the disease re-emerged. Consequently,
      research programs were set up in various places focusing on different features of
      the parasite and the disease. For the first time studies were performed to
      elucidate the molecular repertoire of the parasite. In addition, research has
      been started to investigate the parasite's interaction with its host. New
      diagnostic methods and tools were developed and tested with samples obtained from
      field outbreaks or experimental infections. Some of these studies aimed to
      clarify the introduction of the protozoan parasite into a flock and the
      transmission between birds. Finally, a strong focus was placed on research
      concentrated on the development of new treatment and prophylactic strategies,
      urgently needed to combat the disease. This review aims to summarize recent
      research activities and place them into context with older literature. 

PMID- 25576443
TI  - Compulsion in a different artistic format for a patient with FTD.

PMID- 25576444
TI  - ADHD, autism and neuroradiological complications among phenylketonuric children
      in Upper Egypt.
AB  - The aim of this study is to evaluate the neuropsychological status in a cohort of
      children with early and continuously treated phenylketonuria in Assiut, Upper
      Egypt. The study was implemented in seventy-eight phenylketonuria (PKU) children.
      Only 34 patients met the inclusion criteria. Investigated patients were evaluated
      according to detailed history, neurological examination, Childhood Autism Rating
      Scale, full scale Intelligence Quotient, attention deficit hyperactivity
      disorder, electroencephalography and magnetic resonance imaging (MRI). This study
      concluded that the prognosis for early diagnosed children with PKU treated from
      the first weeks of life is generally good. However, they are at increased risk
      for neurological complications and behavioral problems. So, neonatal screening
      for PKU is highly recommended in Egypt, for early detection and management. In
      addition, neuropsychological and MRI assessments in PKU children should be done. 

PMID- 25576446
TI  - CNS Pseudallescheria boydii infection.

PMID- 25576445
TI  - Clinical utility and applicability of biomarker-based diagnostic criteria for
      Alzheimer's disease: a BeDeCo survey.
AB  - We conducted a survey regarding the medical care of patients with dementia in
      expert settings in Belgium. Open, unrestricted and motivated answers were
      centralized, blindly interpreted and structured into categories. The report of
      the results was then submitted to the participants in subsequent plenary meetings
      and through email. Fourteen experts responded to the questionnaire, confirming
      that recent propositions to modify Alzheimer's disease (AD) diagnostic criteria
      and options have stirred up debate among well-informed and dedicated experts in
      the field. The opinions were not unanimous and illustrate how difficult it is to
      find a standardized method of diagnosing this disease. The responses to the
      survey suggest that application of a step-by-step pragmatic method is used in
      practice. Only when the combination of clinical findings and classical structural
      neuro-imaging is insufficient for a diagnosis or suggests an atypical
      presentation, additional biomarkers are considered. Interestingly, few
      differences, if any, were observed between the use of biomarkers in MCI and in
      AD. In conclusion, the Belgian experts consulted in this survey were generally in
      agreement with the new diagnostic criteria for AD, although some concern was
      expressed about them being too "amyloidocentric". Although the clinical
      examination, including a full neuropsychological evaluation, is still considered
      as the basis for diagnosis, most experts also stated that they use biomarkers to
      help with diagnosis. 

PMID- 25576447
TI  - [Prevalence and risk factors of multi-drug resistant organism colonization among
      long-term care facilities in Gran Canaria (Spain)].
AB  - INTRODUCTION: Multidrug resistant organisms (MDRO) are an important cause of
      nosocomial infections, with complicated clinical-therapeutic management and
      elevated morbidity-mortality, and an increase in healthcare costs. In long term
      care facilities (LTCFs) colonization/infection by MDRO among residents is
      increasing, and they may act as reservoirs and vehicles for the dissemination and
      production of outbreaks by resistant strains in acute hospitals. This study aimed
      at determining the prevalence of carriers of some common MDRO, and identifying
      factors associated with carrier state. MATERIAL AND METHODS: A cross-sectional
      prevalence study was conducted on 235 residents in two LTCFs in the province of
      Las Palmas de Gran Canaria (Canary Islands, Spain) between October and November
      of 2012. The presence of MMR was investigated in nasal, pharyngeal and rectal
      swabs using selective media. Risk factors associated with carrier state were
      calculated using univariate and multivariate analysis. RESULTS: More than one
      third (36.2%) of residents were found to be carriers of >= 1 distinct MDROs. More
      than one-quarter (26.6%) were carriers of ESBL producing Enterobacteriaceae, and
      10.2% were MRSA carriers. Factors found to be associated with colonization by any
      MDRO were: prior colonization or infection by MDRO, hospitalization in the past 3
      months, recurrent infections of the urinary tract, and peripheral arterial
      disease. CONCLUSIONS: The prevalence of MDRO in the LTCFs settings studied is
      greater than that found in the literature, and in particular ESBL producing
      Enterobacteriaceae. Due to the high prevalence of infection/colonization by MDRO,
      it is possible that residents of LTCFs could act as important reservoirs of MDRO,
      and facilitate their spread into the acute care setting.

PMID- 25576449
TI  - Calcium ion as cellular messenger.

PMID- 25576448
TI  - Altered breathing syndrome in heart failure: newer insights and treatment
      options.
AB  - In patients with heart failure (HF), altered breathing patterns, including
      periodic breathing, Cheyne-Stokes breathing, and oscillatory ventilation, are
      seen in several situations. Since all forms of altered breathing cause similar
      detrimental effects on clinical outcomes, they may be considered collectively as
      an "altered breathing syndrome." Altered breathing syndrome should be recognized
      as a comorbid condition of HF and as a potential therapeutic target. In this
      review, we discuss mechanisms and therapeutic options of altered breathing while
      sleeping, while awake at rest, and during exercise. 

PMID- 25576450
TI  - Function of Ca2+ -/calmodulin-dependent protein kinase IV in Ca2+ -stimulated
      neuronal signaling and behavior.
AB  - The activity of Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) is
      sensitive to activity-dependent changes in the level of intracellular Ca(2+).
      Following neuronal stimulation, the activation of CaMKIV may trigger synaptic
      modifications and transcriptional responses, both of which are involved in
      regulating cognitive and emotional behavior. Here, we used CaMKIV knockout (KO)
      neurons and mice to examine the function of CaMKIV in Ca(2+)-stimulated
      intracellular signaling and animal behavior, respectively. Following NMDA
      receptor activation or membrane depolarization, the up-regulation of CREB (cAMP
      responsive element binding protein) and its target gene Bdnf (brain-derived
      neurotrophic factor) was intact in cortical neurons obtained from CaMKIV KO mice.
      CaMKIV KO mice displayed severe impairment in contextual fear memory but normal
      locomotor activity and anxiety level in the contextual training chamber. Although
      CaMKIV KO mice showed normal memory in the standard passive avoidance task, they
      were defective in learning the temporal dissociative passive avoidance task. As
      indicated by the light/dark test and marble-burying test data, CaMKIV KO mice
      showed less anxiety and normal perseveration. In the voluntary wheel-running
      test, CaMKIV KO mice showed normal running time and distance but higher maximal
      running speed. Our results demonstrate the function of CaMKIV in regulating
      different forms of fear memory, anxiety, and certain aspect of motor function. 

PMID- 25576451
TI  - The calcium sensing receptor: from calcium sensing to signaling.
AB  - The Ca(2+)-sensing receptor (the CaSR), a G-protein-coupled receptor, regulates
      Ca(2+) homeostasis in the body by monitoring extracellular levels of Ca(2+)
      ([Ca(2+)]o) and responding to a diverse array of stimuli. Mutations in the Ca(2+)
      sensing receptor result in hypercalcemic or hypocalcemic disorders, such as
      familial hypocalciuric hypercalcemia, neonatal severe primary
      hyperparathyroidism, and autosomal dominant hypocalcemic hypercalciuria.
      Compelling evidence suggests that the CaSR plays multiple roles extending well
      beyond not only regulating the level of extracellular Ca(2+) in the human body,
      but also controlling a diverse range of biological processes. In this review, we
      focus on the structural biology of the CaSR, the ligand interaction sites as well
      as their relevance to the disease associated mutations. This systematic summary
      will provide a comprehensive exploration of how the CaSR integrates extracellular
      Ca(2+) into intracellular Ca(2+) signaling. 

PMID- 25576452
TI  - RGK regulation of voltage-gated calcium channels.
AB  - Voltage-gated calcium channels (VGCCs) play critical roles in cardiac and
      skeletal muscle contractions, hormone and neurotransmitter release, as well as
      slower processes such as cell proliferation, differentiation, migration and
      death. Mutations in VGCCs lead to numerous cardiac, muscle and neurological
      disease, and their physiological function is tightly regulated by kinases,
      phosphatases, G-proteins, calmodulin and many other proteins. Fifteen years ago,
      RGK proteins were discovered as the most potent endogenous regulators of VGCCs.
      They are a family of monomeric GTPases (Rad, Rem, Rem2, and Gem/Kir), in the
      superfamily of Ras GTPases, and they have two known functions: regulation of
      cytoskeletal dynamics including dendritic arborization and inhibition of VGCCs.
      Here we review the mechanisms and molecular determinants of RGK-mediated VGCC
      inhibition, the physiological impact of this inhibition, and recent evidence
      linking the two known RGK functions. 

PMID- 25576453
TI  - Life after the birth of the mitochondrial Na+/Ca2+ exchanger, NCLX.
AB  - Powered by the mitochondrial membrane potential, Ca(2+) permeates the
      mitochondria via a Ca(2+) channel termed Ca(2+) uniporter and is pumped out by a
      Na(+)/Ca(2+) exchanger, both of which are located on the inner mitochondrial
      membrane. Mitochondrial Ca(2+) transients are critical for metabolic activity and
      regulating global Ca(2+) responses. On the other hand, failure to control
      mitochondrial Ca(2+) is a hallmark of ischemic and neurodegenerative diseases.
      Despite their importance, identifying the uniporter and exchanger remains elusive
      and their inhibitors are non-specific. This review will focus on the
      mitochondrial exchanger, initially describing how it was molecularly identified
      and linked to a novel member of the Na(+)/Ca(2+) exchanger superfamily termed
      NCLX. Molecular control of NCLX expression provides a selective tool to determine
      its physiological role in a variety of cell types. In lymphocytes, NCLX is
      essential for refilling the endoplasmic reticulum Ca(2+) stores required for
      antigen-dependent signaling. Communication of NCLX with the store-operated
      channel in astroglia controls Ca(2+) influx and thereby neuro-transmitter release
      and cell proliferation. The refilling of the Ca(2+) stores in the sarcoplasmic
      reticulum, which is controlled by NCLX, determines the frequency of action
      potential and Ca(2+) transients in cardiomyocytes. NCLX is emerging as a hub for
      integrating glucose-dependent Na(+) and Ca(2+) signaling in pancreatic beta
      cells, and the specific molecular control of NCLX expression resolved the
      controversy regarding its role in neurons and beta cells. Future studies on an
      NCLX knockdown mouse model and identification of human NCLX mutations are
      expected to determine the role of mitochondrial Ca(2+) efflux in organ activity
      and whether NCLX inactivation is linked to ischemic and/or neurodegenerative
      syndromes. Structure-function analysis and protein analysis will identify the
      NCLX mode of regulation and its partners in the inner membrane of the
      mitochondria.

PMID- 25576454
TI  - Membrane protein reconstitution for functional and structural studies.
AB  - Membrane proteins are involved in various critical biological processes, and
      studying membrane proteins represents a major challenge in protein biochemistry.
      As shown by both structural and functional studies, the membrane environment
      plays an essential role for membrane proteins. In vitro studies are reliant on
      the successful reconstitution of membrane proteins. This review describes the
      interaction between detergents and lipids that aids the understanding of the
      reconstitution processes. Then the techniques of detergent removal and a few
      useful techniques to refine the formed proteoliposomes are reviewed. Finally the
      applications of reconstitution techniques to study membrane proteins involved in
      Ca(2+) signaling are summarized. 

PMID- 25576456
TI  - Two complexes at the site of microtubule nucleation.

PMID- 25576455
TI  - CLIP: viewing the RNA world from an RNA-protein interactome perspective.
AB  - The pervasive transcription of the genome creates many types of non-coding RNAs
      (ncRNAs). However, we know very little regarding the functions and the regulatory
      mechanisms of these ncRNAs. Exploring the interactions of RNA and RNA binding
      proteins (RBPs) is vital because it can allow us to truly understand how these
      ncRNAs behave in vivo. High-throughput sequencing of RNA isolated by cross
      linking immunoprecipitation (HITS-CLIP or CLIP-seq) and its variants have been
      successfully used as systemic techniques to study RBP binding sites. In this
      review, we will explain the major differences between the CLIP techniques,
      summarize successful applications of these techniques, discuss limitations of
      CLIP, present some suggested solutions and project their promising future roles
      in studying the RNA world. 

PMID- 25576457
TI  - Agreement between cardiologists and fellows in interpretation of ischemic
      electrocardiographic changes in acute myocardial infarction.
AB  - BACKGROUND: Time from symptom onset may not be the best indicator for choosing
      reperfusion therapy for patients presenting with acute ST-elevation myocardial
      infarction (STEMI); consequently ECG-based methods have been developed. METHODS:
      This study evaluated the inter-observer agreement between experienced
      cardiologists and junior doctors in identifying the ECG findings of the pre
      infarction syndrome (PIS) and evolving myocardial infarction (EMI). The ECGs of
      353 STEMI patients were independently analyzed by two cardiologists, one fellow
      in cardiology, one fellow in internal medicine and a medical student. The last
      two were given a half-hour introduction of the PIS/EMI-algorithm. RESULTS: The
      inter-observer reliability between all the investigators was found to be good
      according to kappa statistics (kappa 0.632-0.790) for the whole study population.
      When divided into different subgroups, the inter-observer agreements were from
      good to very good between the cardiologists and the fellow in cardiology (kappa
      0.652 -0.813) and from moderate to good (kappa 0.464-0.784) between the fellow in
      internal medicine, medical student and the others. CONCLUSIONS: The PIS and EMI
      ECG patterns are reliably identified by experienced cardiologists and can be
      easily adopted by junior doctors.

PMID- 25576458
TI  - Prospectively recorded and MedDRA-coded safety data of intravenous
      methylprednisolone therapy in Graves' orbitopathy.
AB  - CONTEXT: Safety of intravenous (IV) steroid pulses in patients with Graves'
      orbitopathy (GO) is still controversial while steroid dose and treatment
      application have not been finalized. Frequency, severity and characterization of
      adverse events (AE) were prospectively analyzed. SETTING: Academic referral
      orbital center with a joint thyroid-eye clinic. PATIENTS: Eighty consecutive and
      unselected patients with active and severe GO. METHODS: During an established
      treatment with IV methylprednisolone (cumulative dose 4.5 g) occurring AE were
      prospectively coded according to the standardized and recognized medical
      dictionary for regulatory activities (MedDRA). Outcome and severity of AE were
      documented. AEs judged as at least possibly related to drug treatment were graded
      as side effect (SE). AEs matching a seriousness criteria as defined by the ICH
      guideline E6 (good clinical practice) were graded as serious. RESULTS: A total of
      38.75% (31/80) of the treated GO patients reported at least one AE while 18
      patients (22.5%) reported at least one SE. All SE were within the safety profile
      of IV methylprednisolone; 31/32 SE (96.87%) were mild-moderate and reversible and
      only 1/80 patient (1.25%) stopped steroid treatment due to exacerbation of her
      depression. Most AE were accessory symptoms of the underlying disease and a few
      only were directly related to IV steroids. Most AEs (90.6%) were graded as mild.
      Only six patients (7.5%) were hospitalized, three of them due to a dysthyroid
      optic neuropathy. CONCLUSIONS: Prospective and standardized evaluation with
      MedDRA and the ICH guideline demonstrated the good pharmacological tolerance and
      low morbidity of this moderate steroid regimen.

PMID- 25576459
TI  - Vitamin D and autoimmunity: what happens in autoimmune polyendocrine syndromes?
AB  - PURPOSE: To evaluate the Vitamin D status of patients with a single autoimmune
      disease and of patients with several autoimmune diseases. METHODS: We enrolled 35
      patients with isolated type 1 diabetes mellitus (T1DM), 60 with autoimmune
      polyendocrine syndromes (APS) including T1DM and 72 control subjects. Among
      patients with APS, 10 were classified as type 2 (Addison's disease + T1DM),
      whereas the other 50 as type 3 (autoimmune thyroid disease + T1DM + other
      autoimmune diseases). Vitamin D (25-OHD) levels were assessed by a
      chemiluminescent immunoassay in all patients and controls on samples drawn in the
      morning of the same months. RESULTS: Both groups of APS and T1DM patients showed
      25-OHD levels significantly lower than healthy controls (p < 0.001 for both vs
      controls), without any significant difference between the two groups (p = 0.80).
      The highest prevalence of vitamin D deficiency (values <20 ng/ml) was observed in
      APS type 3 subgroup (8 out of 50 patients, 16%). CONCLUSIONS: Patients with APS
      present reduced vitamin D circulating levels, but the vitamin D status is not
      different between patients with single or multiple autoimmune diseases. The kind
      of autoimmune disease, rather than the association of several autoimmune
      diseases, may influence negatively the levels of vitamin D. Further prospective
      studies are needed to clarify if impaired vitamin D level is a causal factor in
      the pathogenesis of autoimmune diseases or a consequence of them.

PMID- 25576460
TI  - Pneumococcal pneumonia suppresses allergy development but preserves respiratory
      tolerance in mice.
AB  - Colonization with Streptococcus pneumoniae (S. pneumoniae) is associated with an
      increased risk for recurrent wheeze and asthma. Killed S. pneumoniae showed some
      potential as an effective immunomodulatory therapy in a murine model of asthma.
      Murine studies demonstrated protection against allergic asthma by symbiotic
      bacteria via triggering regulatory T cell response: treatment with killed S.
      pneumoniae resulted in suppressed levels of allergen-specific Th2 cytokines,
      while early immunization generated a protective Th1 response. We investigated the
      impact of lung infection with live S. pneumoniae on both the development and
      maintenance of allergic airway inflammation and respiratory tolerance in mice.
      BALB/c mice were infected intratracheally with S. pneumoniae either prior to or
      after tolerance or allergy were induced, using ovalbumin (OVA) as model allergen.
      Infection of mice with S. pneumoniae prior to sensitization or after
      manifestation of allergic airway inflammation suppressed the development of an
      allergic phenotype as judged by reduced eosinophil counts in bronchoalveolar
      lavage fluid, decreased IgE serum levels and Th2 cytokines, relative to non
      infected allergic control mice. In contrast, infection of mice with S. pneumoniae
      after manifestation of allergic airway inflammation combined with late mucosal re
      challenge did not affect the allergic response. Moreover, induction and
      maintenance of respiratory tolerance to OVA challenge were not altered in S.
      pneumoniae-infected mice, demonstrating that mice remained tolerant to the model
      allergen and were protected from the development of allergic airway inflammation
      regardless of the time point of infection. Our results suggest that a bacterial
      infection may decrease the manifestation of an allergic phenotype not only prior
      to sensitization but also after manifestation of allergic airway inflammation in
      mice, whereas both, induction and maintenance of respiratory tolerance are not
      affected by pneumococcal pneumonia. These data may point to a role for
      undisturbed development and maintenance of mucosal tolerance for the prevention
      of allergic inflammation also in humans. 

PMID- 25576461
TI  - Survey of patients' experiences and their certainty of suspected adverse drug
      reactions.
AB  - BACKGROUND: Patients are best placed to recognize and monitor their own
      experiences of adverse drug reactions (ADRs), however they may need medicines
      information to help them do so. In Thailand patients rarely receive information
      leaflets, but are permitted to report ADRs directly to the regulator. OBJECTIVES:
      To determine frequency of ADRs reported by hospital out-patients, the information
      sources used to evaluate suspected ADRs and patients' confidence in ADR
      identification. SETTING: Srinagarind hospital in Khon Kaen, the second-largest
      province of North-eastern Thailand. METHODS: A questionnaire designed for self
      completion and distributed to out-patients at this tertiary hospital using
      systematic random sampling over a 2-month period. MAIN OUTCOME MEASURES:
      Frequency of reported ADRs, information sources confirming ADRs and degree of
      confidence in ADR identification. RESULTS: Of 1,195 questionnaires distributed,
      1,044 usable responses were obtained (87.4 %). The majority of respondents were
      female (57.1 %) with average age 39.6 +/- 13.6 years. Of 1,044 valid
      questionnaires, 257 (24.7 %) patients indicated they had experienced an ADR with
      high (56.0 %) and moderate (31.9 %) degree of confidence in ADR identification.
      The most frequent causative agent was an anti-infective (19.1 % of the patients).
      Major sources of information used for ADR assessment were healthcare
      professionals (35.5 %) and past ADR experience (25.5 %), with information
      leaflets being used infrequently (14.6 %). CONCLUSIONS: This study showed high
      frequency of ADRs among Thai patients who were mostly confident about casual
      relationships with medicines. Patients mostly used healthcare professionals as
      confirmation source to evaluate suspected ADRs. Reliable medicines information
      sources such as information leaflets should be made more widely available.

PMID- 25576463
TI  - The place of corticosteroids in migraine attack management: A 65-year systematic
      review with pooled analysis and critical appraisal.
AB  - BACKGROUND AND OBJECTIVES: Headaches recur in up to 87% of migraine patients
      visiting the emergency department (ED), making ED recidivism a management
      challenge. We aimed herein to determine the role of corticosteroids in the acute
      management of migraine in the ED and outpatient care. METHODS: Advanced search
      strategies employing PubMed/MEDLINE, Web of Science, and Cochrane Library
      databases inclusive of a relevant gray literature search was employed for
      Clinical Studies and Systematic Reviews by combining the terms "migraine" and
      "corticosteroids" spanning all previous years since the production of synthetic
      corticosteroids ca. 1950 until August 30, 2014. Methods were in accordance with
      MOOSE guidelines. RESULTS: Twenty-five studies (n = 3989, median age 37.5 years,
      interquartile range or IQR 35-41 years; median male:female ratio 1:4.23, IQR
      1:2.1-6.14; 52% ED-based, 56% randomized-controlled) and four systematic reviews
      were included. International Classification of Headache Disorders criteria were
      applied in 64%. Nineteen studies (76%) indicated observed outcome differences
      favoring benefits of corticosteroids, while six (24%) studies indicated non
      inferior outcomes for corticosteroids. Median absolute risk reduction was 30%
      (range 6%-48.2%), and 11% (6%-48.6%) for 24-, and 72-hour headache recurrence,
      respectively. Parenteral dexamethasone was the most commonly (56%) administered
      steroid, at a median single dose of 10 mg (range 4-24 mg). All meta-analyses
      revealed efficacy of adjuvant corticosteroids to various abortive medications
      indicating generalizability. Adverse effects were tolerable. Higher disability,
      status migrainosus, incomplete pain relief, and previous history of headache
      recurrence predicted outcome favorability. CONCLUSIONS: Our literature review
      suggests that with corticosteroid treatment, recurrent headaches become milder
      than pretreated headaches and later respond to nonsteroidal therapy. Single-dose
      intravenous dexamethasone is a reasonable option for managing resistant, severe,
      or prolonged migraine attacks.

PMID- 25576462
TI  - Involving community pharmacists in pharmacy practice research: experiences of
      peer interviewing.
AB  - BACKGROUND: Translation of interest in research into active engagement of
      community pharmacists as research partners/co-researchers remains a challenge.
      Involving pharmacists in specific research techniques such as peer interviewing,
      however, may enhance validity of the results. OBJECTIVE: To enhance community
      pharmacists' involvement in pharmacy practice research through peer interview
      training. METHOD: A subgroup of participants in a multi-phase pharmacy practice
      research project trained to do peer interviews. These pharmacist interviewers
      attended a workshop and were mentored. Comments from their feedback forms and
      ongoing engagement with the Research Associate were thematically analysed.
      RESULTS: Positive themes from five interviewers included the importance of the
      topic and their wish to learn skills beyond their everyday role. The small group
      format of the training day helped to build confidence. Interviewers felt their
      shared professional background helped them to capture relevant comments and probe
      effectively. There were challenges, however, for interviewers to balance research
      activities with their daily work. Interviewers experienced difficulty in securing
      uninterrupted time with interviewees which sometimes affected data quality by
      'rushing'. CONCLUSION: Community pharmacists can be engaged as peer interviewers
      to the benefit of the volunteers and research team, but must be well resourced
      and supported.

PMID- 25576464
TI  - Putting migraine to sleep: Rexants as a preventive strategy.

PMID- 25576466
TI  - New Editor-in-Chief.

PMID- 25576465
TI  - Implication of suspicious cytology in endoscopic ultrasound-guided fine-needle
      aspiration for pancreatic cancer.
AB  - PURPOSE: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become
      a preferred technique to evaluate pancreatic masses. The clinical management of a
      "suspicious for adenocarcinoma" cytological diagnosis is unclear in unresectable
      cases. We sought to determine whether a suspicious diagnosis in the setting of a
      high clinical suspicion of malignancy could be sufficient for initiating non
      operative therapy, such as chemotherapy, in unresectable patients. METHODS:
      Twenty-nine solid pancreatic mass cytology specimens obtained by EUS-FNA with a
      diagnosis of suspicious for adenocarcinoma were identified from 2000 to 2012.
      Pathology, clinical, and radiologic data were analyzed. RESULTS: Additional
      procedures were performed in 21 of the 29 patients. Sixteen of the 21 patients
      had confirmation of malignancy on further tissue sampling and an additional 2 had
      confirmed unresectable cancers during surgical exploration. Three of the 21
      patients had benign diagnoses on subsequent tissue sampling. Of the remaining
      eight patients who did not undergo additional diagnostic procedures, six were
      deemed clinically malignant and treated, one died within a year of the EUS-FNA,
      and one was lost to follow-up. CONCLUSIONS: Consideration of a suspicious
      diagnosis on EUS-FNA of solid pancreatic masses as sufficient for initiating non
      operative therapy is reasonable in the setting of a high clinical suspicion of
      malignancy.

PMID- 25576467
TI  - N-acyl dopamine derivates as lead compound for implementation in transplantation
      medicine.
AB  - Conjugates of fatty acids with ethanolamine, amino acids or monoamine
      neurotransmitters occur widely in nature giving rise to so-called
      endocannabinoids. Anandamide and 2-arachidonoyl glycerol are the best
      characterized endocannabinoids activating both cannabinoid receptors (CB1 and
      CB2) and transient receptor potential vanilloid type 1 (TRPV1) channels
      (anandamide) or activating cannabinoid receptors only (2-arachidonoyl glycerol).
      TRPV1 is also activated by vanilloids, such as capsaicin, and endogenous
      neurolipins, e.g. N-arachidonoyl dopamine (NADA) and N-oleoyl dopamine (OLDA).
      Because donor dopamine treatment has shown to improve transplantation outcome in
      renal and heart recipients, this review will mainly focus on the biological
      activities of N-acyl dopamine derivates (NADD) as potential non-hemodynamic
      alternative for implementation in transplantation medicine. Hence the influence
      of NADD on transplantation relevant entities, i.e. cold inflicted injury,
      cytoprotection, I/R-injury, immune-modulation and inflammation will be
      summarized. The cytoprotective properties of endogenous endocannabinoids in this
      context will be briefly touched upon. 

PMID- 25576469
TI  - Biofilm layers affect the treatment outcomes of NaF and Nano-hydroxyapatite.
AB  - During caries formation, dental biofilms function not only as acid producers but
      also as reservoirs and diffusion barriers for active caries-preventive
      components. The aim of this study was to investigate the influence of biofilms as
      a stagnant layer on the efficacy of NaF and nano-hydroxyapatite (nHA). Biofilms
      of Streptococcus mutans C180-2 were formed on the surfaces of artificially
      demineralized enamel in an active attachment biofilm model. After 2 days of
      biofilm formation, the model was subjected to a pH-cycling schedule, together
      with a control group without biofilms. Specimens were treated for 5 min twice
      daily with water, a 10% nHA slurry, or 18.4 mM NaF. At the end of the pH-cycling
      period, the biofilms were removed for the determination of the viable counts, the
      lactic acid production, and the calcium content. The mineral changes in the
      demineralized enamel blocks were analyzed by transversal microradiography. No
      differences in the biofilm viable counts and lactic acid production were found in
      the different treatment groups. The mean calcium content of the biofilms in the
      nHA group was 60.7 +/- 15.3 mmol/g wet weight, which was approximately 8-fold
      higher than in the other 2 groups. The application of NaF resulted in net
      remineralization, but in the presence of a biofilm, net demineralization was
      observed. In contrast, nHA treatment reduced further demineralization compared
      with the water treatment, but the presence of a biofilm enhanced this effect. In
      conclusion, the presence of biofilms clearly influenced the treatment outcomes of
      anticaries products. Biofilms could either enhance or impede their efficacy. This
      result implies that biofilms should be included in the in vitro tests for the
      preclinical screening of caries-protective agents. 

PMID- 25576468
TI  - Outcomes of midurethral sling procedures in women with mixed urinary
      incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to compare midurethral sling (MUS)
      urinary outcomes in women with stress urinary incontinence (SUI) only versus
      mixed UI (MUI). METHODS: This was a retrospective cohort study of women who
      underwent primary MUS surgery for SUI. MUI was defined as at least "moderately"
      bothersome urgency and stress incontinence on the Urinary Distress Inventory (UDI
      6) subscale of the Pelvic Floor Distress Inventory-20 (PFDI-20). The primary
      outcome was SUI cure defined by a response of "no," "not at all," or "somewhat"
      bothersome SUI on both of the two UDI-6 stress subscale items. Symptom impact was
      assessed using the Urinary Impact Questionnaire (UIQ-7). Multivariable models
      assessed the effect of MUI on SUI outcomes. RESULTS: One thousand one hundred and
      ninety-one primary MUS procedures were reviewed. Seven hundred and fifteen out of
      1,191 (60%) questionnaires were returned and 534 out of 715 (75%) had completed
      baseline and follow-up questionnaires. Mean (+/- SD) follow-up time was 35 +/- 15
      months. Women with MUI had a higher (worse) baseline total score on the UDI-6 (p
      <= 0.001). A lower proportion of women with MUI had SUI success compared with the
      SUI only group (64 vs 84.5%, p <  0.001). On multivariable analyses, women in the
      MUI group were at an increased risk of SUI failure (OR 2.5, 95% CI 1.6, 4.0), but
      greater improvements in UDI-6 (-31.6 +/- 30.6 vs -15.5 +/- 25.1), and UIQ-7
      scores (-21.7 +/- 35.3 vs -15.1 +/- 28.2) compared with women with SUI only (all
      p < 0.02). CONCLUSIONS: Women with MUI are at an increased risk of SUI failure
      after MUS compared with women with SUI only, but experience greater overall
      improvement in the impact of urinary symptoms on the quality of life.

PMID- 25576470
TI  - Involvement of TRPV1 and TRPA1 in incisional intraoral and extraoral pain.
AB  - Thermal and mechanical hypersensitivity in the injured region is a common
      complication. Although it is well known clinically that thermal and mechanical
      sensitivity of the oral mucosa is different from that of the skin, the mechanisms
      underlying injured pain of the oral mucosa remain poorly understood. The
      transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1)
      in primary afferent neurons are known to contribute to pathological pain.
      Therefore, we investigated whether TRPV1 and/or TRPA1 contribute to thermal and
      mechanical hypersensitivity following oral mucosa or whisker pad skin incision.
      Strong heat and mechanical and cold hypersensitivity was caused in the buccal
      mucosa and whisker pad skin following incisions. On day 3 after the incisions,
      the number of TRPV1-immunoreactive (IR) and TRPA1-IR trigeminal ganglion (TG)
      neurons innervating the buccal mucosa and whisker pad skin was significantly
      increased, and the number of TRPV1/TRPA1-IR TG neurons innervating whisker pad
      skin, but not the buccal mucosa, was significantly increased. Administration of
      the TRPV1 antagonist, SB366791, to the incised site produced a significant
      suppression of heat hyperalgesia in both the buccal mucosa and whisker pad skin,
      as well as mechanical allodynia in the whisker pad skin. Administration of the
      TRPA1 antagonist, HC-030031, to the incised site suppressed mechanical allodynia
      and cold hyperalgesia in both the buccal mucosa and whisker pad skin, as well as
      heat hyperalgesia in the whisker pad skin. These findings indicate that altered
      expressions of TRPV1 and TRPA1 in TG neurons are involved in thermal and
      mechanical hypersensitivity following the buccal mucosa and whisker pad skin
      incision. Moreover, diverse changes in the number of TRPV1 and TRPA1 coexpressed
      TG neurons in whisker pad skin-incised rats may contribute to the intracellular
      interactions of TRPV1 and TRPA1 associated with whisker pad skin incision,
      whereas TRPV1 and TRPA1 expression in individual TG neurons is involved in buccal
      mucosa-incised pain. 

PMID- 25576471
TI  - Polymerization behavior of hydrophilic-rich phase of dentin adhesive.
AB  - The 2-fold objectives of this study were 1) to understand whether model
      hydrophobic- and hydrophilic-rich phase mimics of dentin adhesive polymerize
      similarly and 2) to determine which factor, the dimethacrylate component,
      bisphenol A glycerolate dimethacrylate (BisGMA) or photoinitiator concentration,
      has greater influence on the polymerization of the hydrophilic-rich phase mimic.
      Current dentin adhesives are sensitive to moisture, as evidenced by nanoleakage
      in the hybrid layer and phase separation into hydrophobic- and hydrophilic-rich
      phases. Phase separation leads to limited availability of the cross-linkable
      dimethacrylate monomer and hydrophobic photoinitiators within the hydrophilic
      rich phase. Model hydrophobic-rich phase was prepared as a single-phase solution
      by adding maximum wt% deuterium oxide (D2O) to HEMA/BisGMA neat resins containing
      45 wt% 2-hydroxyethyl methacrylate (HEMA). Mimics of the hydrophilic-rich phase
      were prepared similarly but using HEMA/BisGMA neat resins containing 95, 99,
      99.5, and 100 wt% HEMA. The hydrophilic-rich mimics were prepared with standard
      or reduced photoinitiator content. The photoinitiator systems were camphorquinone
      (CQ)/ethyl 4-(dimethylamino)benzoate (EDMAB) with or without [3-(3, 4-dimethyl-9
      oxo-9H-thioxanthen-2-yloxy)-2-hydroxypropyl]trimethylammonium chloride (QTX). The
      polymerization kinetics was monitored using a Fourier transform infrared
      spectrophotometer with a time-resolved collection mode. The hydrophobic-rich
      phase exhibited a significantly higher polymerization rate compared with the
      hydrophilic-rich phase. Postpolymerization resulting in the secondary rate maxima
      was observed for the hydrophilic-rich mimic. The hydrophilic-rich mimics with
      standard photoinitiator concentration but varying cross-linker (BisGMA) content
      showed postpolymerization and a substantial degree of conversion. In contrast,
      the corresponding formulations with reduced photoinitiator concentrations
      exhibited lower polymerization and inhibition/delay of postpolymerization within
      2 h. Under conditions relevant to the wet, oral environment, photoinitiator
      content plays an important role in the polymerization of the hydrophilic-rich
      phase mimic. Since the hydrophilic-rich phase is primarily water and
      monomethacrylate monomer (e.g., HEMA as determined previously), substantial
      polymerization is important to limit the potential toxic response from HEMA
      leaching into the surrounding tissues. 

PMID- 25576472
TI  - Different requirements for Wnt signaling in tongue myogenic subpopulations.
AB  - The tongue is a muscular organ that is essential in vertebrates for important
      functions, such as food intake and communication. Little is known about
      regulation of myogenic progenitors during tongue development when compared with
      the limb or trunk region. In this study, we investigated the relationship between
      different myogenic subpopulations and the function of canonical Wnt signaling in
      regulating these subpopulations. We found that Myf5- and MyoD-expressing myogenic
      subpopulations exist during embryonic tongue myogenesis. In the Myf5-expressing
      myogenic progenitors, there is a cell-autonomous requirement for canonical Wnt
      signaling for cell migration and differentiation. In contrast, the MyoD
      expressing subpopulation does not require canonical Wnt signaling during tongue
      myogenesis. Taken together, our results demonstrate that canonical Wnt signaling
      differentially regulates the Myf5- and MyoD-expressing subpopulations during
      tongue myogenesis. 

PMID- 25576473
TI  - Corrigendum.
AB  - Cagetti MG, Carta G, Cocco F, Sale S, Congiu G, Mura A, Strohmenger L, Lingstrom
      P, Campus G; Italian Experimental Group on Oral Health. 2014. Effect of
      fluoridated sealants on adjacent tooth surfaces: a 30-mo randomized clinical
      trial. J Dent Res. 93(7 Suppl):59S-65S. (Original DOI: 10.1177/0022034514535808)
      There was a typo in two confidence intervals (CIs) in the Abstract. Original
      sentence: Incidence rate ratios (IRRs) were 0.70 (95% confidence interval: 0.50,
      0.68; p < .01) for GIC vs. RB and 0.79 (95% confidence interval: 0.53, 1.04; p =
      .005) for fluoride-RB vs. RB. Corrected sentence: Incidence rate ratios (IRRs)
      were 0.70 (95% confidence interval: 0.50, 0.86; p < .01) for GIC vs. RB and 0.79
      (95% confidence interval: 0.67, 0.89; p = .005) for fluoride-RB vs. RB. There was
      also a typo in two CIs in the Results section. Original sentence: IRR was 0.70
      (95% confidence interval [CI]: 0.50, 0.68; p < .01) between GIC and RB and 0.89
      (95% CI: 0.89, 1.28; p = .10) between GIC and fluoride-RB. IRR between fluoride
      RB and RB groups was 0.79 (95% CI: 0.53, 1.04; p = .005). Corrected sentence: IRR
      was 0.70 (95% confidence interval [CI]: 0.50, 0.86; p < .01) between GIC and RB
      and 0.89 (95% CI: 0.89, 1.28; p = .10) between GIC and fluoride-RB. IRR between
      fluoride-RB and RB groups was 0.79 (95% CI: 0.67, 0.89; p = .005). In the first
      CI, the digits were inadvertently inverted. In the second, the reported CI was
      from another variable not included in the article. The correct CIs are 0.50, 0.86
      and 0.67, 0.89. 

PMID- 25576474
TI  - Phase II Pragmatic Randomized Controlled Trial of Patient-Led Therapies (Mirror
      Therapy and Lower-Limb Exercises) During Inpatient Stroke Rehabilitation.
AB  - BACKGROUND AND OBJECTIVE: Patient-led therapy has the potential to increase the
      amount of therapy patients undertake during stroke rehabilitation and to enhance
      recovery. Our objective was to assess the feasibility and acceptability of 2
      patient-led therapies during the acute stages of stroke care: mirror therapy for
      the upper limb and lower-limb exercises for the lower limb. METHODS: This was a
      blind assessed, multicenter, pragmatic randomized controlled trial of patient-led
      upper-limb mirror therapy and patient-led lower leg exercises. Stroke survivors
      with upper and lower limb limitations, undergoing inpatient rehabilitation and
      able to consent were recruited at least 1 week poststroke. RESULTS: Both
      interventions proved feasible, with >90% retention. No serious adverse events
      were reported. Both groups did less therapy than recommended; typically 5 to 15
      minutes for 7 days or less. Participants receiving mirror therapy (n = 63) tended
      to do less practice than those doing lower-limb exercises (n = 31). Those with
      neglect did 69% less mirror therapy than those without (P = .02), which was not
      observed in the exercise group. Observed between-group differences were modest
      but neglect, upper-limb strength, and dexterity showed some improvement in the
      mirror therapy group. No changes were seen in the lower-limb group. CONCLUSIONS:
      Both patient-led mirror therapy and lower-limb exercises during inpatient stroke
      care are safe, feasible, and acceptable and warrant further investigation.
      Practice for 5 to 15 minutes for 7 days is a realistic prescription unless
      strategies to enhance adherence are included.

PMID- 25576475
TI  - Anterolateral tibial osteotomy for accessing osteochondral lesions of the talus
      in autologous osteochondral transplantation: functional and t2 MRI analysis.
AB  - BACKGROUND: Autologous osteochondral transplantation (AOT) is a primary treatment
      strategy for large or cystic osteochondral lesions of the talus (OLT) or a
      secondary replacement strategy after failed bone marrow stimulation. The
      technique requires perpendicular access to the talar dome, which is often
      difficult to obtain for posterior or lateral lesions. Traditional methods to
      access these areas have required disruption of the syndesmotic complex with
      concern over osteotomy reduction, malalignment, and ligament disruption. An
      alternate to these traditional methods of access is an anterolateral tibial
      osteotomy. The purpose of this study was to report functional and magnetic
      resonance imaging (MRI) outcomes in a series of patients that underwent AOT for
      treatment of an OLT via an anterolateral tibial osteotomy. METHODS: Records of
      patients that underwent an anterolateral tibial osteotomy for AOT were
      retrospectively reviewed. Pre- and postoperative Foot and Ankle Outcome Scores
      (FAOS) and demographic data were recorded. Magnetic resonance observation of
      cartilage repair tissue (MOCART) was used to assess morphologic state of tibial
      cartilage at the repair site of the osteotomy. Quantitative T2 mapping MRI was
      analyzed in the superficial and deep cartilage layers of the repair site of the
      osteotomy and in adjacent normal cartilage to serve as control tissue. Seventeen
      patients with a mean age of 36.9 (range, 17-76) years underwent anterolateral
      tibial osteotomy with a mean follow-up of 64 (range, 29 to 108) months. MOCART
      data were available in 9 of 17 patients, and quantitative T2 mapping was
      available in 6 patients. RESULTS: FAOS significantly improved from an average
      39.2 (range, 14 to 66) out of 100 points preoperatively to 81.2 (range, 19 to 98)
      postoperatively (P < .01). The average MOCART score was 73.9 out of 100 points
      (range, 40 to 100). Quantitative T2 analysis demonstrated relaxation times that
      were not significantly different from the normal native cartilage in both the
      deep half and superficial half of interface repair tissue (P > .05). CONCLUSION:
      This study demonstrated that the anterolateral tibial osteotomy was a reasonable
      alternative for accessing centrolateral or posterolateral OLT for AOT with
      limited morbidity associated with the osteotomy. The evidence demonstrated
      adequate osteotomy and cartilaginous healing with improvement in functional
      outcome scores at medium-term follow-up. LEVEL OF EVIDENCE: Level IV,
      retrospective case series.

PMID- 25576477
TI  - Ectopic Gallbladder.

PMID- 25576476
TI  - A Rare Complication of a Barium-Contrast Study.

PMID- 25576478
TI  - Preventing postoperative recurrence of Crohn's disease: how can we improve
      results?

PMID- 25576480
TI  - Exploring the Legacies of Filmed Patient Narratives: The Interpretation and
      Appropriation of Patient Films by Health Care Staff.
AB  - We trace the legacies of filmed patient narratives that were edited and screened
      to encourage engagement with a participatory quality improvement project in an
      acute hospital setting in England. Using Gabriel's theory of "narrative
      contract," we examine the initial success of the films in establishing common
      grounds for participatory project and later, and more varied, interpretations of
      the films. Over time, the films were interpreted by staff as either useful
      sources of learning by critical reflection, dubious (invalid or unreliable)
      representations of patient experience, or as "closed" items available as
      auditable evidence of completed quality improvement work. We find these
      interpretations of the films to be shaped by the effect of social distance, the
      differential outcomes of project work, and changing organizational agendas. We
      consider the wider conditions of patient narrative as a form of quality
      improvement knowledge with immediate potency and fragile or fluid legitimacy over
      time. 

PMID- 25576481
TI  - "Three in the Room": Embodiment, Disclosure, and Vulnerability in Qualitative
      Research.
AB  - The researcher's body in qualitative research is often absented, an absence that
      can render deceptively tidy research accounts. In this article, I reflect on the
      interplay of embodiment and disclosure in the interview dynamic and the way in
      which my body became an object of inquiry in the research process. Three
      qualitative studies inform the article: the first exploring the experiences of 40
      people living with hepatitis C in New Zealand and Australia, the second
      comprising life-history interviews with 38 people who inject drugs in London, and
      the third following 27 people through hepatitis C treatment in London. Bodily and
      verbal disclosures of my history, as someone with/without hepatitis C and a
      former heroin user, affected the energy of the interview dynamic, also embodied
      understandings of illness and drug use. Disclosure can enhance researcher
      vulnerability and I close with reflection on the ethical implications of
      "enhanced rapport" in the research situation. 

PMID- 25576479
TI  - Multi-ethnic analysis reveals soluble L-selectin may be post-transcriptionally
      regulated by 3'UTR polymorphism: the Multi-Ethnic Study of Atherosclerosis
      (MESA).
AB  - L-Selectin is constitutively expressed on leukocytes and mediates their
      interaction with endothelial cells during inflammation. Previous studies on the
      association of soluble L-selectin (sL-selectin) with cardiovascular disease (CVD)
      are inconsistent. Genetic variants associated with sL-selectin levels may be a
      better surrogate of levels over a lifetime. We explored the association of
      genetic variants and sL-selectin levels in a race/ethnicity stratified random
      sample of 2,403 participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
      Through a genome-wide analysis with additive linear regression models, we found
      that rs12938 on the SELL gene accounted for a significant portion of the protein
      level variance across all four races/ethnicities. To evaluate potential
      additional associations, elastic net models were used for variants located in the
      SELL/SELP/SELE genetic region and an additional two SNPs, rs3917768 and
      rs4987361, were associated with sL-selectin levels in African Americans. These
      variants accounted for a portion of protein variance that ranged from 4 % in
      Hispanic to 14 % in African Americans. To investigate the relationship of these
      variants with CVD, 6,317 subjects were used. No significant association was found
      between any of the identified SNPs and carotid intima-media thickness or presence
      of carotid plaque using linear and logistic regression, respectively. Similarly
      no significant results were found for coronary artery calcium or coronary heart
      disease events. In conclusion, we found that variants within the SELL gene are
      associated with sL-selectin levels. Despite accounting for a significant portion
      of the protein level variance, none of the variants was associated with clinical
      or subclinical CVD.

PMID- 25576482
TI  - Dynamics of the lipid droplet proteome of the Oleaginous yeast rhodosporidium
      toruloides.
AB  - Lipid droplets (LDs) are ubiquitous organelles that serve as a neutral lipid
      reservoir and a hub for lipid metabolism. Manipulating LD formation, evolution,
      and mobilization in oleaginous species may lead to the production of fatty acid
      derived biofuels and chemicals. However, key factors regulating LD dynamics
      remain poorly characterized. Here we purified the LDs and identified LD
      associated proteins from cells of the lipid-producing yeast Rhodosporidium
      toruloides cultured under nutrient-rich, nitrogen-limited, and phosphorus-limited
      conditions. The LD proteome consisted of 226 proteins, many of which are involved
      in lipid metabolism and LD formation and evolution. Further analysis of our
      previous comparative transcriptome and proteome data sets indicated that the
      transcription level of 85 genes and protein abundance of 77 proteins changed
      under nutrient-limited conditions. Such changes were highly relevant to lipid
      accumulation and partially confirmed by reverse transcription-quantitative PCR.
      We demonstrated that the major LD structure protein Ldp1 is an LD marker protein
      being upregulated in lipid-rich cells. When overexpressed in Saccharomyces
      cerevisiae, Ldp1 localized on the LD surface and facilitated giant LD formation,
      suggesting that Ldp1 plays an important role in controlling LD dynamics. Our
      results significantly advance the understanding of the molecular basis of lipid
      overproduction and storage in oleaginous yeasts and will be valuable for the
      development of superior lipid producers. 

PMID- 25576483
TI  - The anillin-related region of Bud4 is the major functional determinant for Bud4's
      function in septin organization during bud growth and axial bud site selection in
      budding yeast.
AB  - The anillin-related protein Bud4 of Saccharomyces cerevisiae is required for
      axial bud site selection by linking the axial landmark to the septins, which
      localize at the mother bud neck. Recent studies indicate that Bud4 plays a role
      in septin organization during cytokinesis. Here we show that Bud4 is also
      involved in septin organization during bud growth prior to cytokinesis, as
      bud4Delta shs1Delta cells displayed an elongated bud morphology and defective
      septin organization at 18 degrees C. Bud4 overexpression also affected septin
      organization during bud growth in shs1Delta cells at 30 degrees C. Bud4 was
      previously thought to associate with the septins via its central region, while
      the C-terminal anillin-related region was not involved in septin association.
      Surprisingly, we found that the central region of Bud4 alone targets to the bud
      neck throughout the cell cycle, unlike full-length Bud4, which localizes to the
      bud neck only during G2/M phase. We identified the anillin-related region to be a
      second targeting domain that cooperates with the central region for proper septin
      association. In addition, the anillin-related region could largely mediate Bud4's
      function in septin organization during bud growth and bud site selection. We show
      that this region interacts with the C terminus of Bud3 and the two segments
      depend on each other for association with the septins. Moreover, like the
      bud4Delta mutant, the bud3Delta mutant genetically interacts with shs1Delta and
      cdc12-6 mutants in septin organization, suggesting that Bud4 and Bud3 may
      cooperate in septin organization during bud growth. These observations provide
      new insights into the interaction of Bud4 with the septins and Bud3. 

PMID- 25576486
TI  - Pharmacological characterization of [3H]VUF11211, a novel radiolabeled small
      molecule inverse agonist for the chemokine receptor CXCR3.
AB  - Chemokine receptor CXCR3 has attracted much attention, as it is thought to be
      associated with a wide range of immune-related diseases. As such, several small
      molecules with different chemical structures targeting CXCR3 have been
      discovered. Despite limited clinical success so far, these compounds serve as
      interesting tools for investigating receptor activation and antagonism.
      Accumulating evidence suggests that many of these compounds are allosteric
      modulators for CXCR3. One feature of allosteric ligands is that the magnitude of
      the mediated allosteric effect is dependent on the orthosteric probe that is
      used. Consequently, there is a risk for incorrect assessment of affinity for
      allosteric modulators with orthosteric radioligands, which has so far been the
      most applied approach for chemokine receptors. Therefore, we aimed to use a small
      molecule allosteric ligand from the piperazinyl-piperidine class, also known as
      VUF11211 [(S)-5-chloro-6-(4-(1-(4-chlorobenzyl)piperidin-4-yl)-3-ethylpiperazin-1
      yl)-N-ethylnicotinamide]. VUF11211 acts as an inverse agonist at a constitutively
      active mutant of CXCR3. Radiolabeling of VUF11211 gave [(3)H]VUF11211, which in
      radioligand binding studies shows high affinity for CXCR3 (Kd = 0.65 nM) and
      reasonably fast association (kon= 0.03 minute(-1)nM(-1)) and dissociation
      kinetics (koff = 0.02 minute(-1)). The application of the [(3)H]VUF11211 to
      assess CXCR3 pharmacology was validated with diverse classes of CXCR3 compounds,
      including both antagonists and agonists, as well as VUF11211 analogs.
      Interestingly, VUF11211 seems to bind to a different population of CXCR3
      conformations compared with the CXCR3 agonists CXC chemokine ligand 11 (CXCL11),
      VUF11418 [1-((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)-N-((2'
      iodobiphenyl-4-yl)methyl)-N,N-dimethylmethanaminium Iodide], and VUF10661 [N-(6
      amino-1-(2,2-diphenylethylamino)-1-oxohexan-2-yl)-2-(4-oxo-4-phenylbutanoyl)
      1,2,3,4-tetrahydroisoquinoline-3-carboxamide]. These findings, taken together,
      indicate that this allosteric inverse agonist radioligand for CXCR3 may
      facilitate the discovery, characterization, and optimization of allosteric
      modulators for the chemokine receptor CXCR3. 

PMID- 25576484
TI  - DNA double-strand breaks and telomeres play important roles in trypanosoma brucei
      antigenic variation.
AB  - Human-infecting microbial pathogens all face a serious problem of elimination by
      the host immune response. Antigenic variation is an effective immune evasion
      mechanism where the pathogen regularly switches its major surface antigen. In
      many cases, the major surface antigen is encoded by genes from the same gene
      family, and its expression is strictly monoallelic. Among pathogens that undergo
      antigenic variation, Trypanosoma brucei (a kinetoplastid), which causes human
      African trypanosomiasis, Plasmodium falciparum (an apicomplexan), which causes
      malaria, Pneumocystis jirovecii (a fungus), which causes pneumonia, and Borrelia
      burgdorferi (a bacterium), which causes Lyme disease, also express their major
      surface antigens from loci next to the telomere. Except for Plasmodium, DNA
      recombination-mediated gene conversion is a major pathway for surface antigen
      switching in these pathogens. In the last decade, more sophisticated molecular
      and genetic tools have been developed in T. brucei, and our knowledge of
      functions of DNA recombination in antigenic variation has been greatly advanced.
      VSG is the major surface antigen in T. brucei. In subtelomeric VSG expression
      sites (ESs), VSG genes invariably are flanked by a long stretch of upstream 70-bp
      repeats. Recent studies have shown that DNA double-strand breaks (DSBs),
      particularly those in 70-bp repeats in the active ES, are a natural potent
      trigger for antigenic variation in T. brucei. In addition, telomere proteins can
      influence VSG switching by reducing the DSB amount at subtelomeric regions. These
      findings will be summarized and their implications will be discussed in this
      review. 

PMID- 25576485
TI  - Functional complementation analyses reveal that the single PRAT family protein of
      trypanosoma brucei is a divergent homolog of Tim17 in saccharomyces cerevisiae.
AB  - Trypanosoma brucei, a parasitic protozoan that causes African trypanosomiasis,
      possesses a single member of the presequence and amino acid transporter (PRAT)
      protein family, which is referred to as TbTim17. In contrast, three homologous
      proteins, ScTim23, ScTim17, and ScTim22, are found in Saccharomyces cerevisiae
      and higher eukaryotes. Here, we show that TbTim17 cannot rescue Tim17, Tim23, or
      Tim22 mutants of S. cerevisiae. We expressed S. cerevisiae Tim23, Tim17, and
      Tim22 in T. brucei. These heterologous proteins were properly imported into
      mitochondria in the parasite. Further analysis revealed that although ScTim23 and
      ScTim17 were integrated into the mitochondrial inner membrane and assembled into
      a protein complex similar in size to TbTim17, only ScTim17 was stably associated
      with TbTim17. In contrast, ScTim22 existed as a protease-sensitive soluble
      protein in the T. brucei mitochondrion. In addition, the growth defect caused by
      TbTim17 knockdown in T. brucei was partially restored by the expression of
      ScTim17 but not by the expression of either ScTim23 or ScTim22, whereas the
      expression of TbTim17 fully complemented the growth defect caused by TbTim17
      knockdown, as anticipated. Similar to the findings for cell growth, the defect in
      the import of mitochondrial proteins due to depletion of TbTim17 was in part
      restored by the expression of ScTim17 but was not complemented by the expression
      of either ScTim23 or ScTim22. Together, these results suggest that TbTim17 is
      divergent compared to ScTim23 but that its function is closer to that of ScTim17.
      In addition, ScTim22 could not be sorted properly in the T. brucei mitochondrion
      and thus failed to complement the function of TbTim17. 

PMID- 25576487
TI  - Transient receptor potential melastatin-3 (TRPM3)-induced activation of AP-1
      requires Ca2+ ions and the transcription factors c-Jun, ATF2, and ternary complex
      factor.
AB  - The steroid pregnenolone sulfate activates the transcription factor activator
      protein-1 (AP-1) via stimulation of transient receptor potential melastatin-3
      (TRPM3) channels. Here, we show that the signaling pathway requires an influx of
      Ca(2+) ions into the cells and a rise in the intracellular Ca(2+) levels. The
      upregulation of AP-1 was attenuated in cells that overexpressed mitogen activated
      protein kinase phosphatase-1, indicating that Ca(2+) ions prolong the signaling
      cascade via activation of mitogen activated protein kinases. On the
      transcriptional level, expression of a dominant-negative mutant of the basic
      region leucine zipper protein c-Jun, a major constituent of the AP-1
      transcription factor complex, or expression of a c-Jun-specific short hairpin RNA
      attenuated pregnenolone sulfate-induced AP-1 activation. In addition, stimulation
      of TRPM3 channels increased the transcriptional activation potential of the basic
      region leucine zipper protein ATF2. Inhibition of ATF2 target gene expression via
      expression of a dominant-negative mutant of ATF2 or expression of an ATF2
      specific short hairpin RNA interfered with TRPM3-mediated stimulation of AP-1.
      Moreover, we show that a dominant-negative mutant of the ternary complex factor
      (TCF) Elk-1 attenuated the upregulation of AP-1 following stimulation of TRPM3
      channels. Thus, c-Jun, ATF2, and TCFs are required to connect the intracellular
      signaling cascade elicited by activation of TRPM3 channels with enhanced
      transcription of AP-1-regulated genes. We conclude that pregnenolone sulfate
      induced TRPM3 channel activation changes the gene expression pattern of the cells
      by activating transcription of c-Jun-, ATF2-, and TCF-controlled genes. 

PMID- 25576488
TI  - Repression of the nuclear receptor small heterodimer partner by steatotic drugs
      and in advanced nonalcoholic fatty liver disease.
AB  - The small heterodimer partner (SHP) (NR0B2) is an atypical nuclear receptor that
      lacks a DNA-binding domain. It interacts with and inhibits many transcription
      factors, affecting key metabolic processes, including bile acid, cholesterol,
      fatty acid, and drug metabolism. Our aim was to determine the influence of
      steatotic drugs and nonalcoholic fatty liver disease (NAFLD) on SHP expression
      and investigate the potential mechanisms. SHP was found to be repressed by
      steatotic drugs (valproate, doxycycline, tetracycline, and cyclosporin A) in
      cultured hepatic cells and the livers of different animal models of NAFLD:
      iatrogenic (tetracycline-treated rats), genetic (glycine N-methyltransferase
      deficient mice), and nutritional (mice fed a methionine- and choline-deficient
      diet). Among the different transcription factors investigated, CCAAT-enhancer
      binding protein alpha (C/EBPalpha) showed the strongest dominant-repressive
      effect on SHP expression in HepG2 and human hepatocytes. Reporter assays revealed
      that the inhibitory effect of C/EBPalpha and steatotic drugs colocalize between 
      340 and -509 base pair of the SHP promoter, and mutation of a predicted
      C/EBPalpha response element at -473 base pair abolished SHP repression by both
      C/EBPalpha and drugs. Moreover, inhibition of major stress signaling pathways
      demonstrated that the mitogen-activated protein kinase kinase 1/2 pathway
      activates, while the phosphatidylinositol 3 kinase pathway represses SHP in a
      C/EBP-dependent manner. We conclude that SHP is downregulated by several
      steatotic drugs and in advanced NAFLD. These conditions can activate signals that
      target C/EBPalpha and consequently repress SHP, thus favoring the progression and
      severity of NAFLD. 

PMID- 25576490
TI  - The impact of weight loss on circulating cytokines in Beagle dogs.
AB  - Chronic low-grade inflammation in obesity is characterized by an increased
      production of pro-inflammatory and chemotactic cytokines that are contributing to
      insulin resistance and related co-morbidities. Cytokines act in networks and
      exhibit pleiotropic effects so we investigated the circulating levels of a wide
      array of cytokines (pro and anti-inflammatory, chemotactic and growth factors) in
      a canine model of weight loss. The dogs served as their own control in order to
      study the impact of weight loss independent of potential confounding factors,
      such as history of excess weight or gender. While low-grade inflammation had been
      previously investigated in obese dogs by measuring changes in adipokines, acute
      phase proteins and key pro-inflammatory cytokines, to the best of our knowledge
      this is the first study to evaluate how weight loss impacts a wide array of
      circulating cytokines. Eighteen overweight Beagle dogs were recruited (six spayed
      females and 12 neutered males), and none of them were grossly obese according to
      the body condition score (BCS). All the dogs reached an ideal weight by the end
      of the program. Parameters were assessed before (baseline), at mid-point (month
      3) and at end-point (month 6). Plasma GM-CSF, IL-2, Il-4, IL-6, IL-7, IL-8, IL
      10, IL-15, IL-18, IFNgamma, IP-10, TNFalpha, monocyte chemotactic protein 1 (MCP
      1), keratinocyte chemokine (KC) were measured with canine multiplex immunoassays.
      Fat mass was assessed by dual energy X-ray absorption (DEXA). Several cytokines
      decreased throughout the weight loss program (p<0.01) and were correlated with
      the percentage of fat measured by DEXA (p<0.05): chemotactic (MCP-1), growth
      factors (GM-CSF, IL-7 and IL-2), and pro-inflammatory (KC and IL-18). We could
      not show trends for several cytokines, possibly because their level may be lower
      than the assay sensitivity: anti-inflammatory (IL-4 and IL-10), and pro
      inflammatory (IL-6 and TNFalpha). In conclusion, while our findings for several
      pro-inflammatory and chemotactic cytokines are in accordance with human and
      rodent studies, we may have identified additional cytokines, such as growth
      factors, related to obesity-induced low-grade inflammation. Considering the
      weight loss was enabled by an adjusted diet, the role of this association of
      cytokines in insulin resistance and related co-morbidities needs to be clarified.
      Our results could help better understand the cytokine biology in dogs, and as
      such are relevant for further elucidating the relationship between immune
      function and metabolism/nutrition. 

PMID- 25576489
TI  - Covalent adduct formation between the plasmalogen-derived modification product 2
      chlorohexadecanal and phloretin.
AB  - Hypochlorous acid added as reagent or generated by the myeloperoxidase (MPO)-H2O2
      Cl(-) system oxidatively modifies brain ether-phospholipids (plasmalogens). This
      reaction generates a sn2-acyl-lysophospholipid and chlorinated fatty aldehydes. 2
      Chlorohexadecanal (2-ClHDA), a prototypic member of chlorinated long-chain fatty
      aldehydes, has potent neurotoxic potential by inflicting blood-brain barrier
      (BBB) damage. During earlier studies we could show that the dihydrochalcone-type
      polyphenol phloretin attenuated 2-ClHDA-induced BBB dysfunction. To clarify the
      underlying mechanism(s) we now investigated the possibility of covalent adduct
      formation between 2-ClHDA and phloretin. Coincubation of 2-ClHDA and phloretin in
      phosphatidylcholine liposomes revealed a half-life of 2-ClHDA of approx. 120min,
      decaying at a rate of 5.9*10(-3)min(-1). NMR studies and enthalpy calculations
      suggested that 2-ClHDA-phloretin adduct formation occurs via electrophilic
      aromatic substitution followed by hemiacetal formation on the A-ring of
      phloretin. Adduct characterization by high-resolution mass spectroscopy confirmed
      these results. In contrast to 2-ClHDA, the covalent 2-ClHDA-phloretin adduct was
      without adverse effects on MTT reduction (an indicator for metabolic activity),
      cellular adenine nucleotide content, and barrier function of brain microvascular
      endothelial cells (BMVEC). Of note, 2-ClHDA-phloretin adduct formation was also
      observed in BMVEC cultures. Intraperitoneal application and subsequent GC-MS
      analysis of brain lipid extracts revealed that phloretin is able to penetrate the
      BBB of C57BL/6J mice. Data of the present study indicate that phloretin scavenges
      2-ClHDA, thereby attenuating 2-ClHDA-mediated brain endothelial cell dysfunction.
      We here identify a detoxification pathway for a prototypic chlorinated fatty
      aldehyde (generated via the MPO axis) that compromises BBB function in vitro and
      in vivo. 

PMID- 25576491
TI  - Extracellular matrix turnover in coronary artery ectasia patients.
AB  - Dysregulation of the metabolism of the extracellular matrix (ECM) may contribute
      to coronary artery ectasia (CAE). This study evaluated the turnover of main ECM
      components and related proteolytic enzymes activities. In this study, thirty
      patients with CAE, 30 patients with coronary artery disease (CAD) and 30 subjects
      with normal coronary arteries (Control) were selected. The following circulating
      ECM metabolism markers were measured: soluble elastin (sElastin), collagen type I
      cross-linked telopeptides (ICTP), procollagen type I carboxy terminal peptide
      (PICP), protocollagen III N-terminal propeptide (PIIINP), and procollagen a1(III)
      C-terminal propeptide (PIIICP). Serum total elastase activity and total matrix
      metalloproteinase (MMP) activity were also determined. The level of sElastin was
      higher in the CAE group than in the CAD and Control groups (P1 = 0.009, P2 =
      0.000). There was no difference in ICTP (P = 0.168) or PIIICP (P = 0.079) among
      the three groups. PICP was significantly elevated in CAE (P1 = 0.001, P2 =
      0.002). PIIINP was also significantly increased in CAE (P1 = 0.002, P2 = 0.007).
      Total elastase activity was higher in the CAE group than in the other two groups
      (P1 = 0.006, P2 = 0.022). Total MMP activity was significantly higher in the CAE
      group than the Control group (P2 = 0.013) but not higher than the CAD group (P1 =
      0.477). In conclusion, within CAE patients the main changes in ECM metabolism
      were increased degradation of elastin fibres and the transition of collagen from
      type III to type I. Elastase and MMPs appear to be associated with this kind of
      ECM turnover.

PMID- 25576494
TI  - Implementation of behavior change techniques in mobile applications for physical
      activity.
AB  - BACKGROUND: Mobile applications (apps) for physical activity are popular and hold
      promise for promoting behavior change and reducing non-communicable disease risk.
      App marketing materials describe a limited number of behavior change techniques
      (BCTs), but apps may include unmarketed BCTs, which are important as well.
      PURPOSE: To characterize the extent to which BCTs have been implemented in apps
      from a systematic user inspection of apps. METHODS: Top-ranked physical activity
      apps (N=100) were identified in November 2013 and analyzed in 2014. BCTs were
      coded using a contemporary taxonomy following a user inspection of apps. RESULTS:
      Users identified an average of 6.6 BCTs per app and most BCTs in the taxonomy
      were not represented in any apps. The most common BCTs involved providing social
      support, information about others' approval, instructions on how to perform a
      behavior, demonstrations of the behavior, and feedback on the behavior. A latent
      class analysis of BCT configurations revealed that apps focused on providing
      support and feedback as well as support and education. CONCLUSIONS: Contemporary
      physical activity apps have implemented a limited number of BCTs and have favored
      BCTs with a modest evidence base over others with more established evidence of
      efficacy (e.g., social media integration for providing social support versus
      active self-monitoring by users). Social support is a ubiquitous feature of
      contemporary physical activity apps and differences between apps lie primarily in
      whether the limited BCTs provide education or feedback about physical activity.

PMID- 25576493
TI  - Regular soda policies, school availability, and high school student consumption.
AB  - BACKGROUND: Beginning in the 2014-2015 school year, all U.S. schools
      participating in federally reimbursable meal programs are required to implement
      new nutrition standards for items sold in competitive venues. Multilevel
      mediation modeling examining direct, mediated, and indirect pathways between
      policy, availability, and student consumption might provide insight into possible
      outcomes of implementing aspects of the new standards. PURPOSE: To employ
      multilevel mediation modeling using state- and school district-level policies
      mandating school soda bans, school soda availability, and student soda
      consumption. METHODS: The 2010-2012 Monitoring the Future surveys obtained
      nationally representative data on high school student soda consumption; school
      administrators provided school soda availability data. State laws and district
      policies were compiled and coded. Analyses conducted in 2014 controlled for state
      , school-, and student-level characteristics. RESULTS: State-district-school
      models found that state bans were associated with significantly lower school soda
      availability (c, p<0.05) but district bans showed no significant associations. No
      significant direct, mediated, or indirect associations between state policy and
      student consumption were observed for the overall sample. Among African American
      high school students, state policy was associated directly with significantly
      lower school soda availability (a, p<0.01), and-indirectly through lower school
      availability-with significantly lower soda consumption (a*b, p<0.05).
      CONCLUSIONS: These analyses indicate state policy focused on regular soda
      strongly affected school soda availability, and worked through changes in school
      availability to decrease soda consumption among African American students, but
      not the overall population.

PMID- 25576492
TI  - Envisioning the dynamics and flexibility of Mre11-Rad50-Nbs1 complex to decipher
      its roles in DNA replication and repair.
AB  - The Mre11-Rad50-Nbs1 (MRN) complex is a dynamic macromolecular machine that acts
      in the first steps of DNA double strand break repair, and each of its components
      has intrinsic dynamics and flexibility properties that are directly linked with
      their functions. As a result, deciphering the functional structural biology of
      the MRN complex is driving novel and integrated technologies to define the
      dynamic structural biology of protein machinery interacting with DNA. Rad50
      promotes dramatic long-range allostery through its coiled-coil and zinc-hook
      domains. Its ATPase activity drives dynamic transitions between monomeric and
      dimeric forms that can be modulated with mutants modifying the ATPase rate to
      control end joining versus resection activities. The biological functions of
      Mre11's dual endo- and exonuclease activities in repair pathway choice were
      enigmatic until recently, when they were unveiled by the development of specific
      nuclease inhibitors. Mre11 dimer flexibility, which may be regulated in cells to
      control MRN function, suggests new inhibitor design strategies for cancer
      intervention. Nbs1 has FHA and BRCT domains to bind multiple interaction partners
      that further regulate MRN. One of them, CtIP, modulates the Mre11 excision
      activity for homologous recombination repair. Overall, these combined properties
      suggest novel therapeutic strategies. Furthermore, they collectively help to
      explain how MRN regulates DNA repair pathway choice with implications for
      improving the design and analysis of cancer clinical trials that employ DNA
      damaging agents or target the DNA damage response. 

PMID- 25576496
TI  - National Institutes of Health funding for behavioral interventions to prevent
      chronic diseases.
AB  - Chronic non-communicable diseases (NCDs) cause the majority of premature deaths,
      disability, and healthcare expenditures in the U.S. Six largely modifiable risk
      behaviors and factors (tobacco use, poor nutrition, physical inactivity, alcohol
      abuse, drug abuse, and poor mental health) account for more than 50% of premature
      mortality and considerably more morbidity and disability. The IOM proposed that
      population burden of disease and preventability should be major determinants of
      the amount of research funding provided by the U.S. NIH. Data on NIH prevention
      funding between fiscal years 2010 and 2012 for human behavioral interventions
      that target the modifiable risk factors of NCDs were analyzed during 2013-2014.
      The NIH prevention portfolio comprises approximately 37% human behavioral studies
      and 63% basic biomedical, genetic, and animal studies. Approximately 65% of
      studies were secondary prevention versus 23% for primary prevention, and 71% of
      studies intervened at the individual and family levels. Diet and exercise were
      the most-studied risk factors (41%), and few studies conducted economic analyses
      (12%). NIH spends an estimated $2.2-$2.6 billion annually (7%-9% of the total of
      $30 billion) on human behavioral interventions to prevent NCDs. Although NIH
      prevention funding broadly aligns with the current burden of disease, overall
      funding remains low compared to funding for treatment, which suggests funding
      misalignment with the preventability of chronic diseases. 

PMID- 25576497
TI  - Monitoring of laser effects on the conduction system by using an open-irrigated
      electrode-laser mapping and ablation catheter: laser catheter mapping.
AB  - AIMS: To assess the laser effects on the conduction system in dog hearts by
      monitoring potential amplitudes (PA) in the focused local electrograms (LEG)
      recorded via pin electrodes (PEs) from the tip of an open-irrigated electrode
      laser mapping and ablation (ELMA) catheter. METHODS AND RESULTS: A total of 54
      mapping guided laser impacts (continuous wave Nd:YAG 1064 nm), at 15 W,
      irrigation rate 30 mL/min, one per dog, were aimed at the sinus nodal (SN) (n =
      20) and atrioventricular (AV) nodal (n = 24) areas, and at the His bundle and
      fascicles (n = 5, each). Laser effects were assessed by monitoring of PA in the
      bipolar focused LEGs. Electrophysiological and electropharmacological tests were
      performed prior to, immediately following, and 3-11 months after the experiments.
      Lesions were evaluated morphometrically and histopathologically. During laser
      application PA gradually dwindled. Radiation times limited to 3-5 s were allowed
      for recovery of PA without affecting functions of the conduction system. Graded
      laser application modulated SN and AV nodal functions permanently, or caused
      stable complete AV conduction block with a mapping-dependent escape rhythm and
      electrical axis deviation after radiation aimed at a fascicle. CONCLUSIONS:
      Monitoring of PAs recorded in the LEG via PE of the ELMA catheter during laser
      application is a unique claim of the laser method that enhances the assessment of
      local electrical activity and ablation efficacy. It allows the assessment of
      laser effects on the conduction system during ablation. By using the ELMA
      catheter described, long-term modulation of SN and AV nodal functions are
      achievable and unwanted complete heart block or fascicular block can be avoided.

PMID- 25576495
TI  - Total and cause-specific mortality of U.S. nurses working rotating night shifts.
AB  - BACKGROUND: Rotating night shift work imposes circadian strain and is linked to
      the risk of several chronic diseases. PURPOSE: To examine associations between
      rotating night shift work and all-cause; cardiovascular disease (CVD); and cancer
      mortality in a prospective cohort study of 74,862 registered U.S. nurses from the
      Nurses' Health Study. METHODS: Lifetime rotating night shift work (defined as >=3
      nights/month) information was collected in 1988. During 22 years (1988-2010) of
      follow-up, 14,181 deaths were documented, including 3,062 CVD and 5,413 cancer
      deaths. Cox proportional hazards models estimated multivariable-adjusted hazard
      ratios (HRs) and 95% CIs. RESULTS: All-cause and CVD mortality were significantly
      increased among women with >=5 years of rotating night shift work, compared to
      women who never worked night shifts. Specifically, for women with 6-14 and >=15
      years of rotating night shift work, the HRs were 1.11 (95% CI=1.06, 1.17) and
      1.11 (95% CI=1.05, 1.18) for all-cause mortality and 1.19 (95% CI=1.07, 1.33) and
      1.23 (95% CI=1.09, 1.38) for CVD mortality. There was no significant association
      between rotating night shift work and all-cancer mortality (HR>=15years=1.08, 95%
      CI=0.98, 1.19) or mortality of any individual cancer, with the exception of lung
      cancer (HR>=15years=1.25, 95% CI=1.04, 1.51). CONCLUSIONS: Women working rotating
      night shifts for >=5 years have a modest increase in all-cause and CVD mortality;
      those working >=15 years of rotating night shift work have a modest increase in
      lung cancer mortality. These results add to prior evidence of a potentially
      detrimental effect of rotating night shift work on health and longevity.

PMID- 25576499
TI  - Adolescent diet and time use clusters and associations with overweight and
      obesity and socioeconomic position.
AB  - Risk factors for adolescent overweight and obesity include low levels of physical
      activity, high levels of sedentary behavior, low fruit and vegetable intake, and
      low socioeconomic position (SEP). To date, the vast majority of research
      investigating associations between lifestyle behaviors and weight status analyze
      dietary and time use factors separately. Our research aimed to describe
      Australian youth time use and diet clusters and explore relationships with weight
      status and SEP (parental education and income). Cluster analysis of the National
      Children's Nutrition and Physical Activity Survey data from Australians aged 9 to
      16 years (random sample n = 1,853) was conducted. Time use data (17 age-adjusted
      time use variables) and dietary data (7 age-adjusted diet variables) were
      collected via 24-hour recalls. Two clusters were associated with a reduced
      frequency of overweight and obesity (the boys' Active Sitter and girls' Healthy
      Academic clusters) and one with an increased frequency of overweight and obesity
      (the boys' Unhealthy cluster). Of these three clusters, two demonstrated
      associations with parental income and/or parental education level. The boys'
      Unhealthy cluster was associated with low SEP status (parental income and
      education), and the girls' Healthy Academic cluster was associated with high
      parental income. Not all unhealthy adolescent clusters were associated with
      overweight and obesity. The findings suggest sex-specific diet and activity
      clusters can be used to identify at-risk subgroups and inform multifaceted
      interventions to address overweight and obesity. 

PMID- 25576498
TI  - Mathematical modeling of combinatorial regulation suggests that apparent positive
      regulation of targets by miRNA could be an artifact resulting from competition
      for mRNA.
AB  - MicroRNAs bind to and regulate the abundance and activity of target messenger RNA
      through sequestration, enhanced degradation, and suppression of translation.
      Although miRNA have a predominantly negative effect on the target protein
      concentration, several reports have demonstrated a positive effect of miRNA,
      i.e., increase in target protein concentration on miRNA overexpression and
      decrease in target concentration on miRNA repression. miRNA-target pair-specific
      effects such as protection of mRNA degradation owing to miRNA binding can explain
      some of these effects. However, considering such pairs in isolation might be an
      oversimplification of the RNA biology, as it is known that one miRNA interacts
      with several targets, and conversely target mRNA are subject to regulation by
      several miRNAs. We formulate a mathematical model of this combinatorial
      regulation of targets by multiple miRNA. Through mathematical analysis and
      numerical simulations of this model, we show that miRNA that individually have a
      negative effect on their targets may exhibit an apparently positive net effect
      when the concentration of one miRNA is experimentally perturbed by
      repression/overexpression in such a multi-miRNA multitarget situation. We show
      that this apparent unexpected effect is due to competition and will not be
      observed when miRNA interact noncompetitively with the target mRNA. This result
      suggests that some of the observed unusual positive effects of miRNA may be due
      to the combinatorial complexity of the system rather than due to any inherently
      unusual positive effect of the miRNA on its target. 

PMID- 25576500
TI  - Bioactive fused heterocycles: Nucleoside analogs with an additional ring.
AB  - The following mini-review summarizes the basic literature data regarding
      synthesis, biological activity, structure-activity relationship, and discussion
      of the mechanisms of action of two major classes of nucleoside analogs with fused
      heterocyclic rings: (i) the ethenonucleosides and their related derivatives of
      the 5,9-dihydro-3-glycosyl-6-alkyl-9-oxo-5H-imidazo[1,2-a]purine type; (ii) the
      bicyclic nucleosides of 6-alkyl-2,3-dihydrofurano[2,3-d]-pyrimidin-2(3H)-one and
      6-alkyl-2,3-dihydropyrrolo[2,3-d]-pyrimidin-2(3H,7H)-one. 

PMID- 25576501
TI  - Chikungunya: here today, where tomorrow?

PMID- 25576502
TI  - Allocate carbon for a reason: priorities are reflected in the 13C/12C ratios of
      plant lipids synthesized via three independent biosynthetic pathways.
AB  - It has long been theorized that carbon allocation, in addition to the carbon
      source and to kinetic isotopic effects associated with a particular lipid
      biosynthetic pathway, plays an important role in shaping the carbon isotopic
      composition ((13)C/(12)C) of lipids (Park and Epstein, 1961). If the latter two
      factors are properly constrained, valuable information about carbon allocation
      during lipid biosynthesis can be obtained from carbon isotope measurements.
      Published work of Chikaraishi et al. (2004) showed that leaf lipids isotopic
      shifts from bulk leaf tissue Deltadelta(13)C(bk-lp) (defined as
      delta(13)C(bulkleaftissue)-delta(13)C(lipid)) are pathway dependent: the
      acetogenic (ACT) pathway synthesizing fatty lipids has the largest isotopic
      shift, the mevalonic acid (MVA) pathway synthesizing sterols the lowest and the
      phytol synthesizing 1-deoxy-D-xylulose 5-phosphate (DXP) pathway gives
      intermediate values. The differences in Deltadelta(13)C(bk-lp) between C3 and C4
      plants Deltadelta(13)C(bk-lp,C4-C3) are also pathway-dependent:
      Deltadelta(13)C(ACT)(bk-lp,C4-C3) > Deltadelta(13)C(DXP(bk-lp,C4-C3) >
      Deltadelta(13)C(MVA)(bk-lp,C4-C3). These pathway-dependent differences have been
      interpreted as resulting from kinetic isotopic effect differences of key but
      unspecified biochemical reactions involved in lipids biosynthesis between C3 and
      C4 plants. After quantitatively considering isotopic shifts caused by (dark)
      respiration, export-of-carbon (to sink tissues) and photorespiration, we propose
      that the pathway-specific differences Deltadelta(13)C(bk-lp,C4-C3) can be
      successfully explained by C4-C3 carbon allocation (flux) differences with
      greatest flux into the ACT pathway and lowest into the MVA pathways (when flux is
      higher, isotopic shift relative to source is smaller). Highest carbon allocation
      to the ACT pathway appears to be tied to the most stringent role of water-loss
      minimization by leaf waxes (composed mainly of fatty lipids) while the lowest
      carbon allocation to the MVA pathway can be largely explained by the fact that
      sterols act as regulatory hormones and membrane fluidity modulators in rather low
      concentrations.

PMID- 25576503
TI  - Orofacial granulomatosis as a presenting feature of Crohn's disease.
AB  - An 11-year-old girl was referred to oral medicine with persistent facial
      swelling. She was diagnosed with orofacial granulomatosis (OFG) and was treated
      conservatively for 7 years, with no evidence of systemic illness. Aged 17 she re
      presented with a flare up of her OFG, watery diarrhoea and fluctuating febrile
      episodes. Inflammatory markers were raised and an MR enterogram revealed terminal
      ileal Crohn's disease. This case highlights that OFG may precede the onset of
      intestinal Crohn's disease.

PMID- 25576504
TI  - Advanced digital subtraction angiography and MR fusion imaging protocol applied
      to accurate placement of flow diverter device.
AB  - In recent years there has been a progressive increase in interventional
      neuroradiology procedures, partially due to improvements in devices, but also to
      the simultaneous development of technologies and radiological images. Cone beam
      CT (Dyna-CT; Siemens) is a method recently used to obtain pseudo CT images from
      digital subtraction angiography (DSA) with a flat panel detector. Using dedicated
      software, it is then possible to merge Dyna-CT images with images from a
      different source. We report here the usefulness of advanced DSA techniques (Syngo
      Dyna CT, three-dimensional DSA iPilot) for the treatment of an intracranial
      aneurysm with a flow diverter device. Merging MR and Dyna-CT images at the end of
      the procedure proved to be a simple and rapid additional method of verifying the
      success of the intervention. 

PMID- 25576505
TI  - Cretinism presenting as a pseudotumour.
AB  - A 43-year-old man from a remote part of India (over 1800 km from our
      institution), presented with a headache of 3 years duration. He was of short
      stature, had delayed puberty and was mentally retarded. On evaluation he was
      detected to have primary hypothyroidism with markedly elevated thyroid
      stimulating hormone titres. A CT of the brain revealed a large sellar mass with
      suprasellar extension into the third ventricle causing obstructive hydrocephalus.
      Surgical intervention was deferred due to absence of visual impairment and the
      presence of gross hypothyroidism. The clinical diagnosis of congenital
      hypothyroidism was confirmed by the absence of radioiodine uptake in the thyroid
      bed. With thyroid hormone replacement therapy, the 'tumour' underwent significant
      reduction in size with the resolution of hydrocephalus thereby favouring a
      potential pituitary pseudotumour. This was an unusual situation of a giant
      pituitary pseudotumour detected in an adult with untreated congenital
      hypothyroidism.

PMID- 25576506
TI  - 'Granuloma gravidarum': persistence in puerperal period an unusual presentation.
AB  - Granuloma gravidarum (GG), an inflammatory lesion, develops in the oral mucosa of
      pregnant women in response to chronic low-grade irritants and hormonal factors. A
      persistent granuloma gravidarum post partum and appropriate management strategies
      are discussed. Patients must be encouraged to undergo regular dental check-ups
      during the gestational period. Simple oral hygiene measures are highly effective
      in combating most oral lesions encountered in pregnancy. 

PMID- 25576507
TI  - Quetiapine-induced myocarditis presenting as acute STEMI.
AB  - An 18-year-old man diagnosed with attention-deficit hyperactivity disorder was
      recently started on quetiapine in addition to regular methylphenidate, which he
      had been taking for a number of years. He presented with chest pain and
      inferolateral ST elevation, and underwent urgent coronary angiography, which
      showed normal coronary arteries. The initial troponin level was raised and an
      inpatient echocardiogram showed mild left ventricular systolic dysfunction with
      no evidence of regional wall motion abnormality. Cardiac MRI showed subepicardial
      late gadolinium enhancement, which was suggestive of myocarditis. Quetiapine and
      methylphenidate were discontinued and the patient was discharged home after 1
      week. He was followed up within 8 weeks with complete recovery and no symptoms.

PMID- 25576508
TI  - Pneumomediastinum and pneumoretroperitoneum: an extremely rare presentation of
      acute appendicitis.
AB  - A 22-year-old woman presented with abdominal pain for 12 days. On examination,
      the abdomen was slightly distended and painful to palpation in the right flank.
      Subsequent abdominal imaging showed inflammation in the right iliac fossa,
      retroperitoneal air pockets with inflammation, and signs of pneumomediastinum.
      Exploratory laparotomy revealed a perforated retrocaecal appendix with abscess
      extending to the retroperitoneum. Surgical intervention involved a right
      hemicolectomy followed by end-to-side anastomosis of the ileum to the transverse
      colon. Histopathological examination of the resected specimen revealed intense
      inflammation of the caecum and no signs of malignancy. The patient was discharged
      in good condition 54 days after surgery.

PMID- 25576509
TI  - Retroperitoneal abscess: an extra-abdominal manifestation.
AB  - Retroperitoneal abscesses are unusual occurrences with occult and insidious
      presentations. There is often a lack of abdominal signs, leading to delays in
      drainage and high mortality rates. We report a case of thigh emphysema in an 88
      year-old patient with diabetes. Prior to admission the patient reported a vague 4
      week history of left thigh pain and an inability to fully weight bear. She
      presented to our emergency department with sepsis and acute kidney impairment. An
      X-ray of her left femur revealed widespread gas between muscular planes. A
      retroperitoneal abscess involving the left renal fossa, psoas, iliacus and upper
      thigh muscles was revealed on an urgent CT scan. The patient was transferred to
      intensive care unit (ICU) and underwent an emergency drainage. Despite ICU the
      patient died 2 days after admission.

PMID- 25576510
TI  - Cone beam CT as an aid to diagnosing mixed radiopaque radiolucent lesions in the
      mandibular incisor region.
AB  - We present two cases where the identities of mixed radiopaque radiolucent lesions
      in the lower incisor region were unclear, although the position of the lesions
      and positive pulp sensitivity tests were suggestive of periapical osseous
      dysplasia. In the first case, the lesion presented as a solitary round mixed
      radiopaque radiolucent periapical lesion, suggestive in some images as periapical
      osseous dysplasia. Cone beam CT (CBCT) provided clear images, which confirmed the
      diagnosis and, additionally, the images showed evidence of initial lesions
      associated with other anterior teeth and some destruction of the labial plate,
      not evident on the conventional radiographs. In the second case, radiopacities
      were identified within the lesion on conventional radiographs, but CBCT imaging
      also showed extensive and unexpected perforation of the lingual plate. Such
      destruction of cortical plates may be a feature of periapical osseous dysplasia,
      which is not visible in conventional radiography. 

PMID- 25576511
TI  - Painful acute radiation thyroiditis induced by 131I treatment of Graves' disease.
AB  - A 44-year-old woman, chronic smoker with Graves' disease was treated with
      radioactive iodine ablation (RAI). One week after the treatment, she presented
      with severe pain in the anterior neck with radiation to the angle of the jaw
      associated with fatigue, tremor and odynophagia. Physical examination
      demonstrated an asymmetric and exquisitely tender thyroid gland. There was no
      laboratory evidence of thyrotoxicosis. Acute radiation thyroiditis was diagnosed.
      Non-steroidal anti-inflammatory drugs and hydrocodone-acetaminophen started
      initially were ineffective for pain control. Prednisone provided relief and was
      continued for 1 month with a tapering dose. Symptoms completely resolved after 1
      month at which time the thyroid remained diffusely enlarged and non-tender. Three
      months following RAI ablation she developed hypothyroid symptoms. Levothyroxine
      was initiated. The patient has remained asymptomatic on continued follow-up care.

PMID- 25576512
TI  - Lamellar macular hole after intravitreal ocriplasmin injection.
AB  - Intravitreal ocriplasmin was recently approved by the Food and Drug
      Administration to achieve medical vitreolysis in the setting of vitreomacular
      adhesion (VMA). We report a case of a 76-year-old woman who developed a lamellar
      macular hole following treatment with intravitreal ocriplasmin injection for VMA.
      A pathophysiological mechanism to explain this previously unreported complication
      of ocriplasmin injection is proposed. 

PMID- 25576513
TI  - Bilateral eccentric vision training on pseudovitelliform dystrophy with
      microperimetry biofeedback.
AB  - Low vision patients with eccentric viewing (EV) use extrafoveal retinal areas to
      compensate for the loss of central vision. Such retinal loci are known as the
      preferred retinal locus (PRL). It is known that EV is accompanied by unstable
      fixation. Microperimetry systems with biofeedback training have been used as a
      rehabilitation aid to improve fixation stability in EV patients. Normally, only
      the best or dominant eye is selected for such rehabilitation. This case report
      describes the rehabilitation on both eyes by means of PRL relocation with MAIA
      microperimetry (Centervue, Padova, Italy) with biofeedback training technology of
      a 74-year-old woman diagnosed with adult pseudovitelliform dystrophy. The patient
      presented binocularly similar anatomical and functional characteristics with the
      PRL located over the dystrophic area. At the end of the 3 months rehabilitation
      period, the PRL was successfully relocated inferiorly from the fovea showing
      relevant visual acuity improvement.

PMID- 25576514
TI  - An unusual treatable cause for proximal muscle weakness.

PMID- 25576515
TI  - Progressive headache in a 48-year-old man.

PMID- 25576516
TI  - Hereditary haemorrhagic telangiectasia.

PMID- 25576517
TI  - Overall survival and renal function after partial and radical nephrectomy among
      older patients with localised renal cell carcinoma: a propensity-matched
      multicentre study.
AB  - BACKGROUND: This study aimed to evaluate the overall survival (OS) rate and renal
      function after radical nephrectomy (RN) and partial nephrectomy (PN) in patients
      aged ?65years. METHODS: Patients who underwent RN (n=622) or PN (n=622) for renal
      cell carcinoma (pT1N0M0) between 1999 and 2011 were propensity-score matched in
      our multicentre database. To investigate the relative effect of PN on OS
      according to age, we divided the patients into two age subgroups (<65 and
      ?65years). The 5-year OS rates and probabilities of freedom from chronic kidney
      disease (CKD III or IV) were estimated using the Kaplan-Meier method and separate
      Cox proportional hazards models. RESULTS: The 5-year OS rates after surgery were
      94.7% for PN and 91.9% for RN in the older patients (P=0.698). The corresponding
      rates in the younger patients were 99.7% for PN and 96.3% for RN (P=0.015). In
      separate Cox hazards models for OS, the older patients who underwent PN were not
      significantly different from their RN-treated counterparts (hazard ratio (HR):
      0.960; 95% confidence interval (CI): 0.277-2.321, P=0.797). Kidney function was
      significantly better preserved after PN than after RN at all ages. However, stage
      IV CKD in the older patients did not occur more frequently in the RN arm than in
      the PN arm. CONCLUSIONS: Although PN was associated with improved renal function
      compared with RN, it did not confer a benefit of higher survival rate in elderly
      patients (?65yearsold).

PMID- 25576518
TI  - The giardial ENTH protein participates in lysosomal protein trafficking and
      endocytosis.
AB  - In the protozoa parasite Giardia lamblia, endocytosis and lysosomal protein
      trafficking are vital parasite-specific processes that involve the action of the
      adaptor complexes AP-1 and AP-2 and clathrin. In this work, we have identified a
      single gene in Giardia encoding a protein containing an ENTH domain that defines
      monomeric adaptor proteins of the epsin family. This domain is present in the
      epsin or epsin-related (epsinR) adaptor proteins, which are implicated in
      endocytosis and Golgi-to-endosome protein trafficking, respectively, in other
      eukaryotic cells. We found that GlENTHp (for G. lamblia ENTH protein) localized
      in the cytosol, strongly interacted with PI3,4,5P3, was associated with the alpha
      subunit of AP-2, clathrin and ubiquitin and was involved in receptor-mediated
      endocytosis. It also bonded PI4P, the gamma subunit of AP-1 and was implicated in
      ER-to-PV trafficking. Alteration of the GlENTHp function severely affected
      trophozoite growth showing an unusual accumulation of dense material in the
      lysosome-like peripheral vacuoles (PVs), indicating that GlENTHp might be
      implicated in the maintenance of PV homeostasis. In this study, we showed
      evidence suggesting that GlENTHp might function as a monomeric adaptor protein
      supporting the findings of other group indicating that GlENTHp might be placed at
      the beginning of the ENTH family. 

PMID- 25576519
TI  - Retinoids induce Nur77-dependent apoptosis in mouse thymocytes.
AB  - Nur77 is a transcription factor, which plays a determinant role in mediating T
      cell receptor-induced cell death of thymocytes. In addition to regulation of
      transcription, Nur77 contributes to apoptosis induction by targeting
      mitochondria, where it can convert Bcl-2, an anti-apoptotic protein into a
      proapoptotic molecule. Previous studies have demonstrated that retinoids are
      actively produced in the mouse thymus and can induce a transcription-dependent
      apoptosis in mouse thymocytes. Here we show that retinoic acids induce the
      expression of Nur77, and retinoid-induced apoptosis is completely dependent on
      Nur77, as retinoids were unable to induce apoptosis in Nur77 null thymocytes. In
      wild-type thymocytes retinoids induced enhanced expression of the apoptosis
      related genes FasL, TRAIL, NDG-1, Gpr65 and Bid, all of them in a Nur77-dependent
      manner. The combined action of these proteins led to Caspase 8-dependent Bid
      cleavage in the mitochondria. In addition, we could demonstrate the Nur77
      dependent induction of STAT1 leading to enhanced Bim expression, and the
      mitochondrial translocation of Nur77 leading to the exposure of the Bcl-2/BH3
      domain. The retinoid-induced apoptosis was dependent on both Caspase 8 and STAT1.
      Our data together indicate that retinoids induce a Nur77-dependent cell death
      program in thymocytes activating the mitochondrial pathway of apoptosis. 

PMID- 25576521
TI  - Finite element analysis of posterior cervical fixation.
AB  - BACKGROUND CONTEXT: Despite largely, used in the past, biomechanical test, to
      investigate the fixation techniques of subaxial cervical spine, information is
      lacking about the internal structural response to external loading. It is not yet
      clear which technique represents the best choice and whether stabilization
      devices can be efficient and beneficial for three-column injuries (TCI).
      HYPOTHESIS: The different posterior cervical fixation techniques (pedicle screw
      PS, lateral mass screw LS, and transarticular screw TS) have respective
      indications. MATERIALS AND METHODS: A detailed, geometrically accurate, nonlinear
      C3-C7 finite element model (FEM) had been successfully developed and validated.
      Then three FEMs were reconstructed from different fixation techniques after C4-C6
      TCI. A compressive preload of 74N combined with a pure moment of 1.8 Nm in
      flexion, extension, left-right lateral bending, and left-right axial rotation was
      applied to the FEMs. RESULTS: The ROM results showed that there were obvious
      significant differences when comparing the different fixation techniques. PS and
      TS techniques can provide better immediate stabilization, compared to LS
      technique. The stress results showed that the variability of von Mises stress in
      the TS fixation device was minimum and LS fixation device was maximum.
      Furthermore, the screws inserted by TS technique had high stress concentration at
      the middle part of the screws. Screw inserted by PS and LS techniques had higher
      stress concentration at the actual cap-rod-screw interface. CONCLUSIONS: The
      research considers that spinal surgeon should first consider using the TS
      technique to treat cervical TCI. If PS technique is used, we should eventually
      prolong the need for external bracing in order to reduce the higher risk of
      fracture on fixation devices. If LS technique is used, we should add anterior
      cervical operation for acquire a better immediate stabilization.

PMID- 25576520
TI  - Looking Back on Rear-Facing Car Seats: Surveying US Parents in 2011 and 2013.
AB  - OBJECTIVE: We sought to determine the age at which US parents first turned their
      child's car seat to face forward and information sources used to make that
      decision at the time of the release of the 2011 guidelines for child passenger
      safety and 30 months later. METHODS: We administered 2 separate cross-sectional
      Web-based surveys of nationally representative panels of US parents in May 2011
      and November 2013. Survey participation rate was 54% in both years. Parents of
      children <=4 years old responded to questions about transitioning from rear
      facing to forward-facing car seats (n = 495 in 2011; n = 521 in 2013). RESULTS:
      In 2011, 33% of parents of 1- to 4-year-old children who had been turned to face
      forward (n = 409) turned at or before 12 months and 16% turned at 2 years or
      older. In 2013, 24% of parents of 1- to 4-year-old children who had been turned
      to face forward (n = 413) turned at or before 12 months and 23% turned at 2 years
      or older. Car seat packaging and clinicians were the most common information
      sources. Demographic characteristics associated with turning to face forward at
      or before 12 months of age in 2011 (parent age, education, household income,
      rural residence) were not significantly associated with transitioning at or
      before 12 months in 2013. CONCLUSIONS: Delaying the transition to a forward
      facing car seat still represents an opportunity to improve passenger safety in
      the United States. As common sources of information, clinicians may be
      influential in a parent's decision to turn their child's car seat to face
      forward.

PMID- 25576524
TI  - Fracture, inflation and floatation embolisation of PTCA balloon.
AB  - This case outlines an unusual complication of coronary intervention, the likely
      mechanisms leading to this and possible retrieval options. It is the first case
      to the best of our knowledge reporting this complication. A 78-year-old Caucasian
      man underwent coronary stenting. During the procedure kinking and subsequent
      fracture of a non-compliant percutaneous transluminal coronary angioplasty (PTCA)
      balloon occurred. Injection of contrast down the guide to opacify the coronary
      arteries resulted in 'inflation' of the balloon with air, and embolisation of the
      inflated balloon into the proximal left anterior descending artery. The embolised
      balloon was retrieved by removal of the guide catheter and wire as a unit. The
      patient had a good angiographic outcome. This case highlights risks associated
      with usage of kinked balloons catheters, and describes for the first time to our
      knowledge, the inflation of a PTCA balloon with air from its shaft within the
      catheter, causing 'floatation' embolisation into the coronary artery. 

PMID- 25576525
TI  - Breast pain in a patient on dialysis: a rare manifestation of calcific uraemic
      arteriolopathy.
AB  - A 63-year-old woman presented with progredient bilateral breast pain. Her medical
      history included rheumatoid arthritis, AA amyloidosis and end-stage renal disease
      treated by peritoneal dialysis. Inflamed skin alterations of the breast and
      laboratory values suggested mastitis non-puerpuralis but antibiotics did not
      resolve the symptoms. Sonography and mammography showed severe vessel
      calcification suggesting calcific uraemic arteriolopathy (calciphylaxis) as a
      rare complication of chronic kidney disease. Treatment included intensified
      haemodialysis, thiosulfate application, analgaesia and wound management leading
      to significant improvement, however, without complete remission. 

PMID- 25576526
TI  - Sore throat... don't forget Lemierre's syndrome.

PMID- 25576528
TI  - Geospatial patterns in human papillomavirus vaccination uptake: evidence from
      uninsured and publicly insured children in North Carolina.
AB  - BACKGROUND: Human papillomavirus (HPV) vaccination coverage is far below the
      national objective set by Healthy People 2020. This paper explores spatial
      patterns in HPV vaccination uptake. METHODS: Secondary data for publicly funded
      HPV vaccinations among age-eligible children from 2008 through 2013 from the
      North Carolina Immunization Registry (NCIR) were used in 2014 in an ecological
      analysis at the ZIP code tabulation area (ZCTA) level. We tested for spatial
      autocorrelation in unadjusted HPV vaccination rates using choropleth maps and
      Moran's I. We estimated nonspatial and spatial negative binomial models with
      spatially correlated random effects adjusted for demographic, economic, and
      healthcare variables drawn from the 2010 U.S. Census Bureau, 2008-2012 American
      Community Survey, 2010 ZIP Business Patterns, and the 2012-2013 Area Resource
      File. RESULTS: The NCIR revealed areas of especially low rates in publicly funded
      HPV vaccinations among uninsured and means-tested, publicly insured children. For
      boys, but not girls, ZCTAs tended to have HPV vaccination rates that were similar
      to their neighbors. This result was partially explained by included ZCTA
      characteristics, but not wholly. CONCLUSIONS: To the extent that the geospatial
      clustering of vaccination rates is due to causal influences from one ZCTA to
      another (e.g., through information networks), targeting interventions to increase
      HPV vaccination in one area could also lead to increases in neighboring areas.
      IMPACT: Spatial targeting of HPV vaccination, especially in clusters of low
      vaccination areas, could be an effective strategy to reduce the spread of HPV and
      related cancers. Cancer Epidemiol Biomarkers Prev; 24(3); 595-602. (c)2015 AACR.

PMID- 25576527
TI  - Paraneoplastic leukemoid reaction in a patient with BRAF V600E-mutated metastatic
      malignant melanoma.
AB  - A paraneoplastic leukemoid reaction is a rare condition of extreme leucocytosis
      in patients with solid malignancies. The differential diagnosis is often a true
      challenge. We present a case of a 56-year old woman with a history of stage IIIA
      malignant melanoma resected in 2004 that was diagnosed in May 2013 with BRAF
      V600E-mutated metastatic disease (left arm mass, lungs and adrenal glands). The
      laboratory findings revealed leucocytosis with granulocytosis that increased
      progressively to values up to 120.0 * 10(9)/L. After a diagnostic work-up, a
      diagnosis of a paraneoplastic leukemoid reaction was established. We report the
      response of leucocytosis to radiation and BRAF inhibitor therapy, albeit short
      lived. To the best of our knowledge, this is the first case report of a
      paraneoplastic leukemoid reaction in metastatic melanoma with characterisation of
      BRAF V600 mutation status. It remains unclear whether the aggressive tumour
      phenotype is related to the leukemoid reaction and whether this is related to the
      BRAF mutation.

PMID- 25576529
TI  - New plasmid-mediated aminoglycoside 6'-N-acetyltransferase, AAC(6')-Ian, and
      ESBL, TLA-3, from a Serratia marcescens clinical isolate.
AB  - OBJECTIVES: Enterobacteriaceae clinical isolates showing amikacin resistance (MIC
      64 to >256 mg/L) in the absence of 16S rRNA methyltransferase (MTase) genes were
      found. The aim of this study was to clarify the molecular mechanisms underlying
      amikacin resistance in Enterobacteriaceae clinical isolates that do not produce
      16S rRNA MTases. METHODS: PCR was performed to detect already-known amikacin
      resistance determinants. Cloning experiments and sequence analyses were performed
      to characterize unknown amikacin resistance determinants. Transfer of amikacin
      resistance determinants was performed by conjugation and transformation. The
      complete nucleotide sequence of the plasmids was determined by next-generation
      sequencing technology. Amikacin resistance enzymes were purified with a column
      chromatography system. The enzymatic function of the purified protein was
      investigated by thin-layer chromatography (TLC) and HPLC. RESULTS: Among the 14
      isolates, 9 were found to carry already-known amikacin resistance determinants
      such as aac(6')-Ia and aac(6')-Ib. Genetic analyses revealed the presence of a
      new amikacin acetyltransferase gene, named aac(6')-Ian, located on a 169 829 bp
      transferable plasmid (p11663) of the Serratia marcescens strain NUBL-11663, one
      of the five strains negative for known aac(6') genes by PCR. Plasmid p11663 also
      carried a novel ESBL gene, named blaTLA-3. HPLC and TLC analyses demonstrated
      that AAC(6')-Ian catalysed the transfer of an acetyl group from acetyl coenzyme A
      onto an amine at the 6'-position of various aminoglycosides. CONCLUSIONS: We
      identified aac(6')-Ian as a novel amikacin resistance determinant together with a
      new ESBL gene, blaTLA-3, on a transferable plasmid of a S. marcescens clinical
      isolate.

PMID- 25576530
TI  - Injury risk factors, screening tests and preventative strategies: a systematic
      review of the evidence that underpins the perceptions and practices of 44
      football (soccer) teams from various premier leagues.
AB  - PURPOSE: To systematically review the scientific level of evidence for the 'Top
      3' risk factors, screening tests and preventative exercises identified by a
      previously published survey of 44 premier league football (soccer) teams. Also,
      to provide an overall scientific level of evidence and graded recommendation
      based on the current research literature. METHODS: A systematic literature search
      (Pubmed [MEDLINE], SportDiscus, PEDRO and Cochrane databases). The quality of the
      articles was assessed and a level of evidence (1++ to 4) was assigned. Level 1++
      corresponded to the highest level of evidence available and 4, the lowest. A
      graded recommendation (A: strong, B: moderate, C: weak, D: insufficient evidence
      to assign a specific recommendation) for use in the practical setting was given.
      RESULTS: Fourteen studies were analysed. The overall level of evidence for the
      risk factors previous injury, fatigue and muscle imbalance were 2++, 4 and
      'inconclusive', respectively. The graded recommendation for functional movement
      screen, psychological questionnaire and isokinetic muscle testing were all 'D'.
      Hamstring eccentric had a weak graded 'C' recommendation, and eccentric exercise
      for other body parts was 'D'. Balance/proprioception exercise to reduce ankle and
      knee sprain injury was assigned a graded recommendation 'D'. CONCLUSIONS: The
      majority of perceptions and practices of premier league teams have a low level of
      evidence and low graded recommendation. This does not imply that these
      perceptions and practices are not important or not valid, as it may simply be
      that they are yet to be sufficiently validated or refuted by research.

PMID- 25576532
TI  - Temporal Cortex Morphology in Mesial Temporal Lobe Epilepsy Patients and Their
      Asymptomatic Siblings.
AB  - Temporal cortex abnormalities are common in patients with mesial temporal lobe
      epilepsy due to hippocampal sclerosis (MTLE+HS) and believed to be relevant to
      the underlying mechanisms. In the present study, we set out to determine the
      familiarity of temporal cortex morphologic alterations in a cohort of MTLE+HS
      patients and their asymptomatic siblings. A surface-based morphometry (SBM)
      method was applied to process MRI data acquired from 140 individuals (50 patients
      with unilateral MTLE+HS, 50 asymptomatic siblings of patients, and 40 healthy
      controls). Using a region-of-interest approach, alterations in temporal cortex
      morphology were determined in patients and their asymptomatic siblings by
      comparing with the controls. Alterations in temporal cortex morphology were
      identified in MTLE+HS patients ipsilaterally within the anterio-medial regions,
      including the entorhinal cortex, parahippocampal gyrus, and temporal pole. Subtle
      but similar pattern of morphology changes with a medium effect size were also
      noted in the asymptomatic siblings. These localized alterations were related to
      volume loss that appeared driven by shared contractions in cerebral cortex
      surface area. These findings indicate that temporal cortex morphologic
      alterations are common to patients and their asymptomatic siblings and suggest
      that such localized traits are possibly heritable. 

PMID- 25576533
TI  - Dissociated Neural Representations of Pain Expressions of Different Races.
AB  - To investigate whether coding pain expressions of own-race and other-race
      individuals engages overlapping or distinct neuronal populations, we recorded
      event-related brain potentials from Chinese and Caucasian adults when viewing an
      adaptor face (with pain or neutral expressions) and a target face (with only pain
      expression) presented in rapid succession. If distinct neuronal populations are
      engaged in coding pain expressions of different races, repetition suppression
      (RS) of neural activity to pain expressions, that is, decreased neural responses
      to target faces preceded by pain versus neutral adaptors, should occur when an
      adaptor and a target are of the same race but not when they are of different
      races. We found that neural responses to adaptor faces at 128-188 ms (P2) and 200
      300 ms (N2) over the frontal/central areas were positively shifted by pain versus
      neutral expressions. Moreover, RS of neural responses to target faces in the
      P2/N2 windows occurred when an adaptor and a target were of the same race but not
      when their racial identities differed, and these effects were observed in both
      Chinese and Caucasian participants. Our results suggest that perception of pain
      expressions of different races may recruit distinct neuronal assemblies at a
      specific stage of the processing stream. 

PMID- 25576531
TI  - Atypical Sulcal Pattern in Children with Developmental Dyslexia and At-Risk
      Kindergarteners.
AB  - Developmental dyslexia (DD) is highly heritable and previous studies observed
      reduced cortical volume, white matter integrity, and functional alterations in
      left posterior brain regions in individuals with DD. The primary sulcal pattern
      has been hypothesized to relate to optimal organization and connections of
      cortical functional areas. It is determined during prenatal development and may
      reflect early, genetically influenced, brain development. We characterize the
      sulcal pattern using graph-based pattern analysis and investigate whether sulcal
      patterns in parieto-temporal and occipito-temporal regions are atypical in
      elementary school-age children with DD and pre-readers/beginning readers
      (preschoolers/kindergarteners) with a familial risk (elementary school-age
      children: n [males/females], age range = 17/11, 84-155 months;
      preschoolers/kindergarteners: 16/15, 59-84 months). The pattern of sulcal basin
      area in left parieto-temporal and occipito-temporal regions was significantly
      atypical (more sulcal basins of smaller size) in children with DD and further
      correlated with reduced reading performance on single- and nonword reading
      measures. A significantly atypical sulcal area pattern was also confirmed in
      younger preschoolers/kindergarteners with a familial risk of DD. Our results
      provide further support for atypical early brain development in DD and suggest
      that DD may originate from altered organization or connections of cortical areas
      in the left posterior regions. 

PMID- 25576534
TI  - Fine Tuning of Synaptic Plasticity and Filtering by GABA Released from
      Hippocampal Autaptic Granule Cells.
AB  - The functional consequence of gamma-aminobutyric acid (GABA) release at mossy
      fiber terminals is still a debated topic. Here, we provide multiple evidence of
      GABA release in cultured autaptic hippocampal granule cells. In ~50% of the
      excitatory autaptic neurons, GABA, VGAT, or GAD67 colocalized with vesicular
      glutamate transporter 1-positive puncta, where both GABAB and GABAA receptors
      (Rs) were present. Patch-clamp recordings showed a clear enhancement of autaptic
      excitatory postsynaptic currents in response to the application of the GABABR
      antagonist CGP58845 only in neurons positive to the selective granule cell marker
      Prox1, and expressing low levels of GAD67. Indeed, GCP non-responsive excitatory
      autaptic neurons were both Prox1- and GAD67-negative. Although the amount of
      released GABA was not sufficient to activate functional postsynaptic GABAARs, it
      effectively activated presynaptic GABABRs that maintain a tonic "brake" on the
      probability of release and on the size of the readily releasable pool and
      contributed to resting potential hyperpolarization possibly through extrasynaptic
      GABAAR activation. The autocrine inhibition exerted by GABABRs on glutamate
      release enhanced both paired-pulse facilitation and post-tetanic potentiation.
      Such GABABR-mediated changes in short-term plasticity confer to immature granule
      cells the capability to modulate their filtering properties in an activity
      dependent fashion, with remarkable consequences on the dynamic behavior of neural
      circuits.

PMID- 25576535
TI  - Planning Movements in Visual and Physical Space in Monkey Posterior Parietal
      Cortex.
AB  - Neurons in the posterior parietal cortex respond selectively for spatial
      parameters of planned goal-directed movements. Yet, it is still unclear which
      aspects of the movement the neurons encode: the spatial parameters of the
      upcoming physical movement (physical goal), or the upcoming visual limb movement
      (visual goal). To test this, we recorded neuronal activity from the parietal
      reach region while monkeys planned reaches under either normal or prism-reversed
      viewing conditions. We found predominant encoding of physical goals while fewer
      neurons were selective for visual goals during planning. In contrast, local field
      potentials recorded in the same brain region exhibited predominant visual goal
      encoding, similar to previous imaging data from humans. The visual goal encoding
      in individual neurons was neither related to immediate visual input nor to visual
      memory, but to the future visual movement. Our finding suggests that action
      planning in parietal cortex is not exclusively a precursor of impending physical
      movements, as reflected by the predominant physical goal encoding, but also
      contains spatial kinematic parameters of upcoming visual movement, as reflected
      by co-existing visual goal encoding in neuronal spiking. The co-existence of
      visual and physical goals adds a complementary perspective to the current
      understanding of parietal spatial computations in primates. 

PMID- 25576536
TI  - Sensory Deviancy Detection Measured Directly Within the Human Nucleus Accumbens.
AB  - Rapid changes in the environment evoke a comparison between expectancy and actual
      outcome to inform optimal subsequent behavior. The nucleus accumbens (NAcc), a
      key interface between the hippocampus and neocortical regions, is a candidate
      region for mediating this comparison. Here, we report event-related potentials
      obtained from the NAcc using direct intracranial recordings in 5 human
      participants while they listened to trains of auditory stimuli differing in their
      degree of deviation from repetitive background stimuli. NAcc recordings revealed
      an early mismatch signal (50-220 ms) in response to all deviants. NAcc activity
      in this time window was also sensitive to the statistics of stimulus deviancy,
      with larger amplitudes as a function of the level of deviancy. Importantly, this
      NAcc mismatch signal also predicted generation of longer latency scalp potentials
      (300-400 ms). The results provide direct human evidence that the NAcc is a key
      component of a network engaged in encoding statistics of the sensory
      environmental. 

PMID- 25576537
TI  - Pretraining Cortical Thickness Predicts Subsequent Perceptual Learning Rate in a
      Visual Search Task.
AB  - We report that preexisting individual differences in the cortical thickness of
      brain areas involved in a perceptual learning task predict the subsequent
      perceptual learning rate. Participants trained in a motion-discrimination task
      involving visual search for a "V"-shaped target motion trajectory among inverted
      "V"-shaped distractor trajectories. Motion-sensitive area MT+ (V5) was
      functionally identified as critical to the task: after 3 weeks of training,
      activity increased in MT+ during task performance, as measured by functional
      magnetic resonance imaging. We computed the cortical thickness of MT+ from
      anatomical magnetic resonance imaging volumes collected before training started,
      and found that it significantly predicted subsequent perceptual learning rates in
      the visual search task. Participants with thicker neocortex in MT+ before
      training learned faster than those with thinner neocortex in that area. A similar
      association between cortical thickness and training success was also found in
      posterior parietal cortex (PPC). 

PMID- 25576546
TI  - Evidence-based dental education and systematic reviews.

PMID- 25576545
TI  - Rapid fluorescence in situ hybridisation (FISH) for HER2 (ERBB2) assessment in
      breast and gastro-oesophageal cancer.
AB  - Evaluation of HER2 (ERBB2) gene amplification or protein expression is standard
      of care in breast (BR) and advanced stage gastro-oesophageal cancers to identify
      patients eligible for anti-HER2 therapies. Here, we evaluate a rapid fluorescence
      in situ hybridisation (FISH) technology (HER2 instant quality (IQ) FISH pharmDx
      Kit) for detection of HER2 in patients with BR and gastro-oesophageal cancer
      using 30 FFPE samples that had been previously evaluated with the PathVysion HER2
      DNA Probe Kit. Cases were scored as positive (HER2:CEN-17 >=2.0), negative
      (HER2:CEN-17 <2.0) or equivocal according to the ASCO/CAP 2013 BR cancer
      guidelines. Ten samples were positive for HER2 amplification while 20 were
      negative; none were equivocal. The IQ FISH was able to detect low level
      amplification (HER2:CEN-17 ratio 2.4). The HER2 IQ FISH pharmDx Kit is a FDA
      approved kit that offers a rapid turnaround time (approximately 3.5 h) and in our
      laboratory was 100% concordant with prior PathVysion results.

PMID- 25576547
TI  - Characteristics of the Cochrane Oral Health Group systematic reviews.
AB  - The Cochrane Oral Health Group (COHG) was formed in 1994 with the aim of
      producing systematic reviews that primarily include oral health randomized
      controlled trials (RCTs). The purpose of this cross-sectional study was to
      characterize reviews published by the COHG. In September 2013, the COHG database
      was accessed, and all publications were downloaded. Reviews with no studies
      identified according to the inclusion criteria were labeled "empty reviews." The
      complete Cochrane database included a total of 5,697 reviews, of which the COHG
      database included 142 reviews. Of these 142, 69 (48.6%) did not reach a
      conclusion, including 20 (14.1%) that were identified as empty reviews. Of the
      122 non-empty reviews, 116 (95.1%) were based exclusively on RCTs. The median
      number of RCTs and patients included in the non-empty reviews were seven and 489,
      respectively. The median number of included RCTs and patients for reviews that
      reached conclusions were 12 and 934, respectively, and there were five RCTs and
      211 patients for reviews without conclusions. Overall, the characteristics of the
      Cochrane oral health reviews (OH-CSRs) were similar to Cochrane reviews published
      in other disciplines (All-CSRs). The authors observed a significant difference in
      the median number of RCTs and patients included when reviews that reached
      conclusions were separated from those that did not. A greater proportion of empty
      reviews were present in OH-CSRs compared with All-CSRs. Turning the Cochrane
      reviews into a tool that is more relevant in clinical practice will require
      implementation of a methodology allowing inclusion of non-RCTs while controlling
      for possible bias. 

PMID- 25576538
TI  - Planning Ahead: Object-Directed Sequential Actions Decoded from Human
      Frontoparietal and Occipitotemporal Networks.
AB  - Object-manipulation tasks (e.g., drinking from a cup) typically involve
      sequencing together a series of distinct motor acts (e.g., reaching toward,
      grasping, lifting, and transporting the cup) in order to accomplish some
      overarching goal (e.g., quenching thirst). Although several studies in humans
      have investigated the neural mechanisms supporting the planning of visually
      guided movements directed toward objects (such as reaching or pointing), only a
      handful have examined how manipulatory sequences of actions-those that occur
      after an object has been grasped-are planned and represented in the brain. Here,
      using event-related functional MRI and pattern decoding methods, we investigated
      the neural basis of real-object manipulation using a delayed-movement task in
      which participants first prepared and then executed different object-directed
      action sequences that varied either in their complexity or final spatial goals.
      Consistent with previous reports of preparatory brain activity in non-human
      primates, we found that activity patterns in several frontoparietal areas
      reliably predicted entire action sequences in advance of movement. Notably, we
      found that similar sequence-related information could also be decoded from pre
      movement signals in object- and body-selective occipitotemporal cortex (OTC).
      These findings suggest that both frontoparietal and occipitotemporal circuits are
      engaged in transforming object-related information into complex, goal-directed
      movements. 

PMID- 25576549
TI  - Dental students' perceptions of and experiences with prosthodontics: ten
      graduating classes at one institution.
AB  - It is important for members of the dental specialties to understand what
      motivates students to enter the specialty in order to ensure its continuing
      development and ability to meet patient needs. The aim of this study was to
      compare ten graduating classes at Harvard School of Dental Medicine (HSDM)
      regarding students' experiences with and perceptions of prosthodontics and
      factors influencing those interested in pursuing prosthodontics as a specialty.
      In 2013, HSDM students in the classes of 2012-16 were surveyed, achieving a
      response rate of 81%. Survey questions sought information regarding specialty
      choice, factors influencing the choice, student experiences with prosthodontics,
      and student perceptions of the dental disciplines. Responses were compared to
      those from a prior study of the HSDM classes of 2007-11. The responses showed a
      decrease in negative student experiences with prosthodontics. The students
      regarded prosthodontics highly for its impact on patient quality of life;
      however, students interested in pursuing prosthodontics as a specialty decreased.
      All students said provider enjoyment was most important in choice of specialty.
      Cost of program, patient type, and program location were factors that especially
      influenced students interested in prosthodontics. The improved student
      experiences with and perspectives on prosthodontics may be a result of a
      curriculum change that led to more prosthodontics procedures and case completions
      by students. The fall in students interested in prosthodontics may have resulted
      from prosthodontic faculty transitions that occurred when the survey was
      conducted, as well as large debt burdens in spite of the fact that
      prosthodontists' earnings are among the highest in dentistry. Faculty must
      educate and mentor students about the realities of the profession, provide
      positive learning experiences in the field, and encourage students who enjoy
      prosthodontics to pursue specialty training. 

PMID- 25576548
TI  - Assessment of the calibration of periodontal diagnosis and treatment planning
      among dental students at three dental schools.
AB  - Calibration in diagnosis and treatment planning is difficult to achieve due to
      variations that exist in clinical interpretation. To determine if dental faculty
      members are consistent in teaching how to diagnose and treat periodontal disease,
      variations among dental students can be evaluated. A previous study reported high
      variability in diagnoses and treatment plans of periodontal cases at Indiana
      University School of Dentistry. This study aimed to build on that one by
      extending the research to two additional schools: Marquette University School of
      Dentistry and West Virginia University School of Dentistry. Diagnosis and
      treatment planning by 40 third- and fourth-year dental students were assessed at
      each of the schools. Students were asked to select the diagnosis and treatment
      plans on a questionnaire pertaining to 11 cases. Their responses were compared
      using chi-square tests, and multirater kappa statistics were used to assess
      agreement between classes and between schools. Logistic regression models were
      used to evaluate the effects of school, class year, prior experience, and
      GPA/class rank on correct responses. One case had a statistically significant
      difference in responses between third- and fourth-year dental students. Kappas
      for school agreement and class agreement were low. The students from Indiana
      University had higher diagnosis and treatment agreements than the Marquette
      University students, and the Marquette students fared better than the West
      Virginia University students. This study can help restructure future periodontal
      courses for a better understanding of periodontal diagnosis and treatment
      planning. 

PMID- 25576550
TI  - Do dental students use optimal study strategies?
AB  - Research on human learning has shown that repeated retrieval practice or self
      testing maximizes learning. However, recent studies have found undergraduate
      students to be largely unaware of the benefits of self-testing. The aim of this
      study was to examine dental students' study strategies and utilization of
      retrieval techniques for learning. All second-year dental students at New York
      University College of Dentistry were invited to participate. Of the total 360
      students, 66 completed the two-question survey, for a response rate of 18.3%. The
      first question asked students to choose from a list of twelve study strategies
      the ones they used and to rank their top five in order of personal preference.
      Repeated reading was the most frequently used strategy with 83.3% of students
      reporting that they used it and 43.9% naming it as their top strategy. Of these
      students, 45.5% indicated that they self-tested while studying, but none
      indicated it was their number one strategy. The second question asked students
      how they would study after reading a textbook chapter for the first time. They
      were asked to choose one option from three possibilities: going back and
      restudying, self-testing (with the possibility of restudying afterward), or some
      other strategy. On this question, 25.8% chose restudying, 45.5% chose self
      testing, and 28.8% indicated they would use another study strategy. Thus, 54.6%
      of the students reported they would not test themselves after reading a textbook
      chapter. Of those who chose self-testing, only seven students indicated they
      would do so to improve learning. The results of this study suggest that the
      students lacked sufficient awareness of the superiority of self-testing for
      learning. 

PMID- 25576551
TI  - Perceptions of uncivil student behavior in dental education.
AB  - Students and faculty members in the health professions classroom are expected to
      exhibit professional behaviors that are conducive to maintaining a positive
      learning environment, but there is little published research concerning
      incivility in the area of dental education. The aim of this study was to evaluate
      differences in perceptions of incivility between dental faculty and students,
      between students in different courses of study, and between students in different
      years of dental study. The study utilized an anonymous electronic survey of all
      dental faculty and administrators and all dental, dental hygiene, and dental
      laboratory technology students at a single institution. The survey instrument
      contained questions concerning perceived uncivil behavior in the classroom and
      clinical settings. Response rates were 54% for faculty and administrators and
      ranged from 60% to 97% for students in various years and programs. The results
      were analyzed based on gender, course of study, year of study, and ethnicity.
      Significant differences were found regarding perceptions of civil behaviour
      between faculty and students, male and female students, the year of study, and
      the course of study. These differences point to the need for further research as
      well as administrative leadership and faculty development to define guidelines in
      this area in order to ensure a positive learning environment. 

PMID- 25576552
TI  - Teaching dental students to interact with survivors of traumatic events:
      development of a two-day module.
AB  - Dentists are likely to treat patients who have experienced a wide range of
      traumatic life events, including child abuse and neglect, domestic violence,
      sexual assault, elder abuse, and exposure to combat. In order to effectively
      treat survivors of traumatic events, dentists must understand how these patients
      may present in oral health settings, the basic mandated reporting requirements
      related to abuse and neglect, and communication strategies to help engage trauma
      survivors in dental treatment. A traditional lecture-format educational module on
      trauma-informed care was developed and implemented for second-year dental
      students (N=92) at one U.S. dental school, after which a needs assessment was
      performed (all 92 students participated). This assessment then informed
      development of an enhanced module for the subsequent group of second-year dental
      students (N=102) at the same school. The revised (final) module was more
      interactive in nature, expanded to multiple sessions, and included more
      discussion of mandated reporting and appropriate dentist-patient communication in
      relation to traumatic events. All 102 students participated in assessments of the
      revised module. Comparison of pre and post tests and needs assessments between
      the initial and final modules indicated that the extended, more interactive final
      module was more effective in meeting the educational objectives. Results showed
      that the final module increased the students' knowledge in the health-related
      manifestations of traumatic events and slightly improved their confidence levels
      in treating survivors of trauma. Dentists who are prepared to deliver trauma
      informed care may help individual patients feel more at ease and increase
      engagement in regular preventive care. Suggestions for future educational efforts
      in this area are discussed. 

PMID- 25576553
TI  - Preparation time and perceptions of Brazilian specialists and dental students
      regarding simulated root canals for endodontic teaching: a preliminary study.
AB  - The aim of this preliminary study was to evaluate the desirability of alternative
      models of artificial teeth versus extracted natural teeth for use in preclinical
      dental education. Specifically, the study was designed to compare the preparation
      time and perceptions of difficulty of undergraduate dental students and
      endodontists in carrying out root canal preparations on resin models (both clear
      and opaque) and extracted natural teeth. Twenty participants-ten fifth-year
      students at a Brazilian dental school and ten endodontists with at least five
      years' experience in the specialty-performed root canal instrumentation on two
      samples of each model. Preparation times were recorded, and the participants
      completed a questionnaire about the anatomical and physical characteristics of
      these models. The results showed that the time required for performing endodontic
      procedures in the natural teeth was higher than in the alternative models. The
      perceptions of the students and specialists regarding some topics on the
      questionnaire were significantly different. The students had more positive
      opinions about artificial teeth made of opaque resin, while the specialists had
      more positive opinions about simulated root canals in clear resin blocks. This
      study suggests that neither of the alternative models fulfilled requirements to
      replace natural teeth in endodontic teaching; improvements are still necessary to
      accomplish this goal. 

PMID- 25576554
TI  - Background, training experiences, and career plans of U.S. periodontal residents:
      report of a web-based survey.
AB  - The purpose of this cross-sectional study was to survey the backgrounds and
      perspectives of U.S. periodontal residents in 2012. A 64-item web-based survey
      was distributed to all periodontal residents in the United States (544 residents
      enrolled in 54 graduate programs) via email in March 2012. Data on the residents'
      demographics, experiences during graduate periodontal training, and goals were
      collected and analyzed, and percentages were calculated. The survey had a 19.1%
      response rate. Most of the respondents (74%) had graduated from international
      dental schools, and 81.7% were in combined programs (clinical training combined
      with a Master's degree, PhD, or other doctoral degree). Almost one-fourth of the
      responding residents (24%) reported a total debt of more than $300,000 after
      graduation. More than 60% of the respondents planned to practice in a private
      setting as an associate, partner, or solo practice owner. The responding
      residents reported having chosen their graduate programs based mainly on the
      programs' clinical education and reputation (72% and 48%, respectively). Future
      studies will determine educational trends and outcomes for periodontal residents
      in the longer term. 

PMID- 25576555
TI  - Training needs for general dentistry residents to place and restore two-implant
      retained mandibular overdentures.
AB  - Implant therapy is rapidly becoming a standard of care for replacing missing
      dentition. Predoctoral dental curricula include some training in the implant
      restorative phase but offer limited exposure to the surgical phase, so it is
      important for postdoctoral general dentistry residency programs to provide
      competency training in all phases of implant therapy. The aim of this study was
      to determine the training needed for general dentistry residents to achieve
      competence in this area, specifically by defining the number of clinical
      experiences necessary in both the surgical and prosthetic phases of implant
      retained mandibular overdenture construction (IRMOD). Fifteen Advanced Education
      in General Dentistry (AEGD) residents at one academic dental institution placed
      two implants in a total of 50 patients with edentulous mandibles and subsequently
      restored them with IRMOD. The supervising faculty member and the residents
      evaluated the competency level on a five-point scale after each implant placement
      and prosthetic case completion. According to the faculty evaluations, the
      residents achieved surgical competence after placing two implants in four to six
      cases and prosthetic management competence after restoring two to four cases of
      IRMOD. All 50 patients were satisfied with the treatment outcomes of IRMOD. This
      study concluded that general dentistry residents could potentially achieve
      competence in both the surgical and prosthetic phases of implant therapy while
      enrolled in an AEGD program. 

PMID- 25576556
TI  - Attitudes and perceptions of U.S. dental students and faculty regarding dental
      licensure.
AB  - The aim of this study was to assess the attitudes and perceptions of U.S. dental
      students and faculty members about National Board Dental Examination (NBDE)
      pass/fail reporting, an Integrated NBDE, clinical examinations, licensure process
      and strategies, and validity of licensure. A survey instrument consisting of ten
      statements with response options on a five-point Likert scale and a free-text
      comment section was developed and distributed through SurveyMonkey. A total of
      411 students and 186 faculty members from ten U.S. dental schools participated,
      with an estimated response rate of 17%. Faculty and student responses were
      compared using the Mann-Whitney U test. These students' and faculty members'
      attitudes and perceptions were similar. Both groups showed mixed attitudes about
      NBDE scores as pass/fail, rather than numerical scores. The Integrated NBDE
      solicited mixed opinions and concerns that it would be complicated and stressful
      because students would be challenged to memorize information from earlier years.
      However, a single national clinical examination was highly preferred by both
      groups, preferably with simulated rather than real patients. Other strategies,
      such as background checks and continuing education requirements, were supported
      by both groups. Most of the licensure process strategies and policies were
      supported by both student and faculty respondents in the dental schools surveyed.

PMID- 25576557
TI  - The influence of examiner type on dental students' OSCE scores.
AB  - The purpose of this study was to evaluate the difference in grading of objective
      structured clinical examinations (OSCEs) at Harvard School of Dental Medicine
      (HSDM) by full-time faculty examiners, part-time faculty examiners, and
      postgraduate resident examiners. The OSCE is an evaluation of clinical competence
      and is used as a multidisciplinary examination at HSDM. Two examiners are
      selected for each of ten disciplines. Evaluators meet to review the case before
      the OSCE is given, and faculty examiners are given the opportunity to write exam
      questions based on the students' expected level of knowledge and ability. All
      examiners also meet on the day of the OSCE to review the case and discuss
      relevant issues. Students are randomly assigned to examiners and meet with one
      examiner at a time in each discipline during the examination. Analysis of OSCE
      scores on four exams given to HSDM students between 2012 and 2013 suggests that
      part-time faculty members tended to score students significantly higher than full
      time faculty members or postgraduate residents. This may be a result of reduced
      contact time between students and the part-time faculty although it may also
      point to a need for more efforts in calibration of the part-time faculty members
      who take part in the OSCE. 

PMID- 25576558
TI  - Attitudes towards shared learning of trainee dental technicians and undergraduate
      dental students.
AB  - The challenges of health care are increasingly complex and subject to frequent
      change. Meeting these demands requires that health professionals work in
      partnership with each other and the patient. One way of contributing to this is
      for students to learn together. However, effective teamwork requires an education
      system that helps to foster understanding among all those entering the health
      workforce. The purpose of this study was to investigate the attitudes towards
      shared learning of undergraduate dental students and trainee dental technicians
      in a university dental school/hospital in the United Kingdom. Twenty-five trainee
      dental technicians and 75 undergraduate dental students took part in the study
      over five academic years. Data were collected using structured questionnaires. A
      100% response rate was achieved from the questionnaires. The results indicated
      the majority of students recognized the benefits of shared learning and viewed
      the acquisition of teamworking skills as useful for their future working lives,
      beneficial to the care of their patients, and likely to enhance professional
      working relationships. The study also found a positive association of being
      valued as an individual in the dental team by all student groups. Future dental
      curricula should provide opportunities to develop effective communication between
      these two groups and encourage teamworking opportunities. These opportunities
      need to be systematically developed in the dental curriculum to achieve the
      desired goals. 

PMID- 25576560
TI  - Multiscale 3-D + T intracranial aneurysmal flow vortex detection.
AB  - OBJECTIVE: Characteristics of vortices within intracranial aneurysmal flow
      patterns have been associated with increased risk of rupture. The classifications
      of these vortex characteristics are commonly based upon qualitative scores, and
      are, therefore, subjective to user interpretation. We present a quantitative
      method for automatic time-resolved characterization of 3-D flow patterns and
      vortex detection within aneurysms. METHODS: Our approach is based upon the
      combination of kernel deconvolution and Jacobian analysis of the velocity field.
      The deconvolution approach is accurate in detecting vortex centers but cannot
      discriminate between vortices and high-shear regions. Therefore, this approach is
      combined with analysis of the Jacobian of the velocity field. Scale-space theory
      is used to evaluate aneurysmal flow velocity fields at various scales. RESULTS:
      The proposed algorithm is applied to computational fluid dynamics and time
      resolved 3-D phase-contrast magnetic resonance imaging of aneurysmal flow.
      CONCLUSION: Results show that the proposed algorithm efficiently detects,
      visualizes, and quantifies vortices in intracranial aneurysmal velocity patterns
      at multiple scales and follows the temporal evolution of these patterns.
      SIGNIFICANCE: Quantitative analysis performed with this method has the potential
      to reduce interobserver variability in aneurysm classification.

PMID- 25576561
TI  - Extraction of time and frequency features from grip force rates during dexterous
      manipulation.
AB  - The time course of grip force from object contact to onset of manipulation has
      been extensively studied to gain insight into the underlying control mechanisms.
      Of particular interest to the motor neuroscience and clinical communities is the
      phenomenon of bell-shaped grip force rate (GFR) that has been interpreted as
      indicative of feedforward force control. However, this feature has not been
      assessed quantitatively. Furthermore, the time course of grip force may contain
      additional features that could provide insight into sensorimotor control
      processes. In this study, we addressed these questions by validating and applying
      two computational approaches to extract features from GFR in humans: 1) fitting a
      Gaussian function to GFR and quantifying the goodness of the fit [root-mean
      square error, (RMSE)]; and 2) continuous wavelet transform (CWT), where we
      assessed the correlation of the GFR signal with a Mexican Hat function.
      Experiment 1 consisted of a classic pseudorandomized presentation of object mass
      (light or heavy), where grip forces developed to lift a mass heavier than
      expected are known to exhibit corrective responses. For Experiment 2, we applied
      our two techniques to analyze grip force exerted for manipulating an inverted T
      shaped object whose center of mass was changed across blocks of consecutive
      trials. For both experiments, subjects were asked to grasp the object at either
      predetermined or self-selected grasp locations ("constrained" and "unconstrained"
      task, respectively). Experiment 1 successfully validated the use of RMSE and CWT
      as they correctly distinguished trials with versus without force corrective
      responses. RMSE and CWT also revealed that grip force is characterized by more
      feedback-driven corrections when grasping at self-selected contact points. Future
      work will examine the application of our analytical approaches to a broader range
      of tasks, e.g., assessment of recovery of sensorimotor function following
      clinical intervention, interlimb differences in force control, and force
      coordination in human-machine interactions. 

PMID- 25576562
TI  - Evaluation of peritoneal microbubble oxygenation therapy in a rabbit model of
      hypoxemia.
AB  - Alternative extrapulmonary oxygenation technologies are needed to treat patients
      suffering from severe hypoxemia refractory to mechanical ventilation. We
      previously demonstrated that peritoneal microbubble oxygenation (PMO), in which
      phospholipid-coated oxygen microbubbles (OMBs) are delivered into the peritoneal
      cavity, can successfully oxygenate rats suffering from a right pneumothorax. This
      study addressed the need to scale up the procedure to a larger animal with a
      splanchnic cardiac output similar to humans. Our results show that PMO therapy
      can double the survival time of rabbits experiencing complete tracheal occlusion
      from 6.6 +/-0.6 min for the saline controls to 12.2 +/-3.0 min for the bolus PMO
      treated cohort. Additionally, we designed and tested a new peritoneal delivery
      system to circulate OMBs through the peritoneal cavity. Circulation achieved a
      similar survival benefit to bolus delivery under these conditions. Overall, these
      results support the feasibility of the PMO technology to provide extrapulmonary
      ventilation for rescue of severely hypoxic patients. 

PMID- 25576564
TI  - Spatially Sparse, Temporally Smooth MEG Via Vector l0 .
AB  - In this paper, we describe a new method for solving the magnetoencephalography
      inverse problem: temporal vector l0-penalized least squares (TV-L0LS). The method
      calculates maximally sparse current dipole magnitudes and directions via spatial
      l0 regularization on a cortically-distributed source grid, while constraining the
      solution to be smooth with respect to time. We demonstrate the utility of this
      method on real and simulated data by comparison to existing methods. 

PMID- 25576563
TI  - Health service use, out-of-pocket payments and catastrophic health expenditure
      among older people in India: the WHO Study on global AGEing and adult health
      (SAGE).
AB  - BACKGROUND: Healthcare financing through out-of-pocket payments and inequities in
      healthcare utilisation are common in low and middle income countries (LMICs).
      Given the dearth of pertinent studies on these issues among older people in
      LMICs, we investigated the determinants of health service use, out-of-pocket and
      catastrophic health expenditures among older people in one LMIC, India. METHODS:
      We accessed data from a nationally representative, multistage sample of 2414
      people aged 65 years and older from the WHO's Study on global AGEing and adult
      health in India. Sociodemographic characteristics, health profiles, health
      service utilisation and out-of-pocket health expenditure were assessed using
      standard instruments. Multivariate zero-inflated negative binomial regression
      models were used to evaluate the determinants of health service visits.
      Multivariate Heckman sample selection regression models were used to assess the
      determinants of out-of-pocket and catastrophic health expenditures. RESULTS: Out
      of-pocket health expenditures were higher among participants with disability and
      lower income. Diabetes, hypertension, chronic pulmonary disease, heart disease
      and tuberculosis increased the number of health visits and out-of-pocket health
      expenditures. The prevalence of catastrophic health expenditure among older
      people in India was 7% (95% CI 6% to 8%). Older men and individuals with chronic
      diseases were at higher risk of catastrophic health expenditure, while access to
      health insurance lowered the risk. CONCLUSIONS: Reducing out-of-pocket health
      expenditure among older people is an important public health issue, in which
      social as well as medical determinants should be prioritised. Enhanced public
      health sector performance and provision of publicly funded insurance may protect
      against catastrophic health expenses and healthcare inequities in India.

PMID- 25576565
TI  - Robust Prostate Segmentation Using Intrinsic Properties of TRUS Images.
AB  - Accurate segmentation is usually crucial in transrectal ultrasound (TRUS) image
      based prostate diagnosis; however, it is always hampered by heavy speckles.
      Contrary to the traditional view that speckles are adverse to segmentation, we
      exploit intrinsic properties induced by speckles to facilitate the task, based on
      the observations that sizes and orientations of speckles provide salient cues to
      determine the prostate boundary. Since the speckle orientation changes in
      accordance with a statistical prior rule, rotation-invariant texture feature is
      extracted along the orientations revealed by the rule. To address the problem of
      feature changes due to different speckle sizes, TRUS images are split into
      several arc-like strips. In each strip, every individual feature vector is
      sparsely represented, and representation residuals are obtained. The residuals,
      along with the spatial coherence inherited from biological tissues, are combined
      to segment the prostate preliminarily via graph cuts. After that, the
      segmentation is fine-tuned by a novel level sets model, which integrates (1) the
      prostate shape prior, (2) dark-to-light intensity transition near the prostate
      boundary, and (3) the texture feature just obtained. The proposed method is
      validated on two 2-D image datasets obtained from two different sonographic
      imaging systems, with the mean absolute distance on the mid gland images only
      1.06+/-0.53 mm and 1.25+/-0.77 mm, respectively. The method is also extended to
      segment apex and base images, producing competitive results over the state of the
      art.

PMID- 25576566
TI  - A learning framework for age rank estimation based on face images with scattering
      transform.
AB  - This paper presents a cost-sensitive ordinal hyperplanes ranking algorithm for
      human age estimation based on face images. The proposed approach exploits
      relative-order information among the age labels for rank prediction. In our
      approach, the age rank is obtained by aggregating a series of binary
      classification results, where cost sensitivities among the labels are introduced
      to improve the aggregating performance. In addition, we give a theoretical
      analysis on designing the cost of individual binary classifier so that the
      misranking cost can be bounded by the total misclassification costs. An efficient
      descriptor, scattering transform, which scatters the Gabor coefficients and
      pooled with Gaussian smoothing in multiple layers, is evaluated for facial
      feature extraction. We show that this descriptor is a generalization of
      conventional bioinspired features and is more effective for face-based age
      inference. Experimental results demonstrate that our method outperforms the state
      of-the-art age estimation approaches.

PMID- 25576567
TI  - SaCoseg: object cosegmentation by shape conformability.
AB  - In this paper, an object cosegmentation method based on shape conformability is
      proposed. Different from the previous object cosegmentation methods which are
      based on the region feature similarity of the common objects in image set, our
      proposed SaCoseg cosegmentation algorithm focuses on the shape consistency of the
      foreground objects in image set. In the proposed method, given an image set where
      the implied foreground objects may be varied in appearance but share similar
      shape structures, the implied common shape pattern in the image set can be
      automatically mined and regarded as the shape prior of those unsatisfactorily
      segmented images. The SaCoseg algorithm mainly consists of four steps: 1) the
      initial Grabcut segmentation; 2) the shape mapping by coherent point drift
      registration; 3) the common shape pattern discovery by affinity propagation
      clustering; and 4) the refinement by Grabcut with common shape constraint. To
      testify our proposed algorithm and establish a benchmark for future work, we
      built the CoShape data set to evaluate the shape-based cosegmentation. The
      experiments on CoShape data set and the comparison with some related
      cosegmentation algorithms demonstrate the good performance of the proposed
      SaCoseg algorithm.

PMID- 25576568
TI  - Consistency-driven alternating optimization for multigraph matching: a unified
      approach.
AB  - The problem of graph matching (GM) in general is nondeterministic polynomial
      complete and many approximate pairwise matching techniques have been proposed.
      For a general setting in real applications, it typically requires to find the
      consistent matching across a batch of graphs. Sequentially performing pairwise
      matching is prone to error propagation along the pairwise matching sequence, and
      the sequences generated in different pairwise matching orders can lead to
      contradictory solutions. Motivated by devising a robust and consistent multiple
      GM model, we propose a unified alternating optimization framework for multi-GM.
      In addition, we define and use two metrics related to graphwise and pairwise
      consistencies. The former is used to find an appropriate reference graph, which
      induces a set of basis variables and launches the iteration procedure. The latter
      defines the order in which the considered graphs in the iterations are
      manipulated. We show two embodiments under the proposed framework that can cope
      with the nonfactorized and factorized affinity matrix, respectively. Our multi-GM
      model has two major characters: 1) the affinity information across multiple
      graphs are explored in each iteration by fixing part of the matching variables
      via a consistency-driven mechanism and 2) the framework is flexible to
      incorporate various existing pairwise GM solvers in an out-of-box fashion, and
      also can proceed with the output of other multi-GM methods. The experimental
      results on both synthetic data and real images empirically show that the proposed
      framework performs competitively with the state-of-the-art.

PMID- 25576569
TI  - Temporally coherent superresolution of textured video via dynamic texture
      synthesis.
AB  - This paper addresses the problem of hallucinating the missing high-resolution
      (HR) details of a low-resolution (LR) video while maintaining the temporal
      coherence of the reconstructed HR details using dynamic texture synthesis (DTS).
      Most existing multiframe-based video superresolution (SR) methods suffer from the
      problem of limited reconstructed visual quality due to inaccurate subpixel motion
      estimation between frames in an LR video. To achieve high-quality reconstruction
      of HR details for an LR video, we propose a texture-synthesis (TS)-based video SR
      method, in which a novel DTS scheme is proposed to render the reconstructed HR
      details in a temporally coherent way, which effectively addresses the temporal
      incoherence problem caused by traditional TS-based image SR methods. To further
      reduce the complexity of the proposed method, our method only performs the TS
      based SR on a set of key frames, while the HR details of the remaining nonkey
      frames are simply predicted using the bidirectional overlapped block motion
      compensation. After all frames are upscaled, the proposed DTS-SR is applied to
      maintain the temporal coherence in the HR video. Experimental results demonstrate
      that the proposed method achieves significant subjective and objective visual
      quality improvement over state-of-the-art video SR methods.

PMID- 25576570
TI  - Progressive halftone watermarking using multilayer table lookup strategy.
AB  - In this paper, a halftoning-based multilayer watermarking of low computational
      complexity is proposed. An additional data-hiding technique is also employed to
      embed multiple watermarks into the watermark to be embedded to improve the
      security and embedding capacity. At the encoder, the efficient direct binary
      search method is employed to generate 256 reference tables to ensure the output
      is in halftone format. Subsequently, watermarks are embedded by a set of
      optimized compressed tables with various textural angles for table lookup. At the
      decoder, the least mean square metric is considered to increase the differences
      among those generated phenotypes of the embedding angles and reduce the required
      number of dimensions for each angle. Finally, the naive Bayes classifier is
      employed to collect the possibilities of multilayer information for classifying
      the associated angles to extract the embedded watermarks. These decoded
      watermarks can be further overlapped for retrieving the additional hidden-layer
      watermarks. Experimental results show that the proposed method requires only 8.4
      ms for embedding a watermark into an image of size 512*512 , under the 32-bit
      Windows 7 platform running on 4GB RAM, Intel core i7 Sandy Bridge with 4GB RAM
      and IDE Visual Studio 2010. Finally, only 2 MB is required to store the proposed
      compressed reference table. 

PMID- 25576571
TI  - Learning multiple linear mappings for efficient single image super-resolution.
AB  - Example learning-based superresolution (SR) algorithms show promise for restoring
      a high-resolution (HR) image from a single low-resolution (LR) input. The most
      popular approaches, however, are either time- or space-intensive, which limits
      their practical applications in many resource-limited settings. In this paper, we
      propose a novel computationally efficient single image SR method that learns
      multiple linear mappings (MLM) to directly transform LR feature subspaces into HR
      subspaces. In particular, we first partition the large nonlinear feature space of
      LR images into a cluster of linear subspaces. Multiple LR subdictionaries are
      then learned, followed by inferring the corresponding HR subdictionaries based on
      the assumption that the LR-HR features share the same representation
      coefficients. We establish MLM from the input LR features to the desired HR
      outputs in order to achieve fast yet stable SR recovery. Furthermore, in order to
      suppress displeasing artifacts generated by the MLM-based method, we apply a fast
      nonlocal means algorithm to construct a simple yet effective similarity-based
      regularization term for SR enhancement. Experimental results indicate that our
      approach is both quantitatively and qualitatively superior to other application
      oriented SR methods, while maintaining relatively low time and space complexity.

PMID- 25576572
TI  - Stretch Evoked Potentials in Healthy Subjects and After Stroke: A Potential
      Measure for Proprioceptive Sensorimotor Function.
AB  - Sensory feedback is of vital importance in motor control, yet rarely assessed in
      diseases with impaired motor function like stroke. Muscle stretch evoked
      potentials (StrEPs) may serve as a measure of cortical sensorimotor activation in
      response to proprioceptive input. The aim of this study is: 1) to determine early
      and late features of the StrEP and 2) to explore whether StrEP waveform and
      features can be measured after stroke. Consistency of StrEP waveforms and
      features was evaluated in 22 normal subjects. StrEP features and similarity
      between hemispheres were evaluated in eight subacute stroke subjects. StrEPs of
      normal subjects had a consistent shape across conditions and sessions (mean cross
      correlation waveforms > 0.75). Stroke subjects showed heterogeneous StrEP
      waveforms. Stroke subjects presented a normal early peak (40 ms after movement
      onset) but later peaks had abnormal amplitudes and latencies. No significant
      differences between stroke subjects with good and poor motor function were found
      (P > 0.14). With the consistent responses of normal subjects the StrEP meets a
      prerequisite for potential clinical value. Recording of StrEPs is feasible even
      in subacute stroke survivors with poor motor function. How StrEP features relate
      to clinical phenotypes and recovery needs further investigation.

PMID- 25576574
TI  - A remotely-controlled locomotive IC driven by electrolytic bubbles and wireless
      powering.
AB  - A batteryless remotely-controlled locomotive IC utilizing electrolytic bubbles as
      propelling force is realized in 0.35 MUm CMOS technology. Without any external
      components, such as magnets and on-board coils, the bare IC is wirelessly powered
      and controlled by a 10 MHz ASK modulated signal with RS232 control commands to
      execute movement in four moving directions and with two speeds. The receiving
      coil and electrolysis electrodes are all integrated on the locomotive chip. The
      experiment successfully demonstrated that the bare IC moved on the surface of an
      electrolyte with a speed up to 0.3 mm/s and change moving directions according to
      the commands. The total power consumptions of the chip are 207.4 MUW and 180 MU W
      while the output electrolysis voltages are 2 V and 1.3 V, respectively. 

PMID- 25576573
TI  - A fully integrated nose-on-a-chip for rapid diagnosis of ventilator-associated
      pneumonia.
AB  - Ventilator-associated pneumonia (VAP) still lacks a rapid diagnostic strategy.
      This study proposes installing a nose-on-a-chip at the proximal end of an
      expiratory circuit of a ventilator to monitor and to detect metabolite of
      pneumonia in the early stage. The nose-on-a-chip was designed and fabricated in a
      90-nm 1P9M CMOS technology in order to downsize the gas detection system. The
      chip has eight on-chip sensors, an adaptive interface, a successive approximation
      analog-to-digital converter (SAR ADC), a learning kernel of continuous restricted
      Boltzmann machine (CRBM), and a RISC-core with low-voltage SRAM. The
      functionality of VAP identification was verified using clinical data. In total,
      76 samples infected with pneumonia (19 Klebsiella, 25 Pseudomonas aeruginosa, 16
      Staphylococcus aureus, and 16 Candida) and 41 uninfected samples were collected
      as the experimental group and the control group, respectively. The results
      revealed a very high VAP identification rate at 94.06% for identifying healthy
      and infected patients. A 100% accuracy to identify the microorganisms of
      Klebsiella, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida from VAP
      infected patients was achieved. This chip only consumes 1.27 mW at a 0.5 V supply
      voltage. This work provides a promising solution for the long-term unresolved
      rapid VAP diagnostic problem. 

PMID- 25576575
TI  - 2.5D heterogeneously integrated microsystem for high-density neural sensing
      applications.
AB  - Heterogeneously integrated and miniaturized neural sensing microsystems are
      crucial for brain function investigation. In this paper, a 2.5D heterogeneously
      integrated bio-sensing microsystem with MU-probes and embedded through-silicon
      via (TSVs) is presented for high-density neural sensing applications. This
      microsystem is composed of MU-probes with embedded TSVs, 4 dies and a silicon
      interposer. For capturing 16-channel neural signals, a 24 * 24 MU-probe array
      with embedded TSVs is fabricated on a 5*5 mm(2) chip and bonded on the back side
      of the interposer. Thus, each channel contains 6 * 6 MU -probes with embedded
      TSVs. Additionally, the 4 dies are bonded on the front side of the interposer and
      designed for biopotential acquisition, feature extraction and classification via
      low-power analog front-end (AFE) circuits, area-power-efficient analog-to-digital
      converters (ADCs), configurable discrete wavelet transforms (DWTs), filters, and
      a MCU. An on-interposer bus ( MU-SPI) is designed for transferring data on the
      interposer. Finally, the successful in-vivo test demonstrated the proposed 2.5D
      heterogeneously integrated bio-sensing microsystem. The overall power of this
      microsystem is only 676.3 MUW for 16-channel neural sensing. 

PMID- 25576577
TI  - Passivity of switched recurrent neural networks with time-varying delays.
AB  - This paper is concerned with the passivity analysis for switched neural networks
      subject to stochastic disturbances and time-varying delays. First, using the
      multiple Lyapunov functions method, a state-dependent switching law is designed
      to present a stochastic passivity condition. Second, a hysteresis switching law
      involving both the current state and the previous value of the switching signal
      are presented to avoid chattering resulted from the state-dependent switching.
      Third, based on the average dwell-time approach, a class of switching signals is
      determined to guarantee the switched neural network stochastically passive.
      Finally, three numerical examples are provided to illustrate the characteristics
      of three proposed switching laws. 

PMID- 25576578
TI  - Twin support vector machine for clustering.
AB  - The twin support vector machine (TWSVM) is one of the powerful classification
      methods. In this brief, a TWSVM-type clustering method, called twin support
      vector clustering (TWSVC), is proposed. Our TWSVC includes both linear and
      nonlinear versions. It determines k cluster center planes by solving a series of
      quadratic programming problems. To make TWSVC more efficient and stable, an
      initialization algorithm based on the nearest neighbor graph is also suggested.
      The experimental results on several benchmark data sets have shown a comparable
      performance of our TWSVC. 

PMID- 25576579
TI  - Dynamic State Estimation of Power Systems With Quantization Effects: A Recursive
      Filter Approach.
AB  - In this paper, a recursive filter algorithm is developed to deal with the state
      estimation problem for power systems with quantized nonlinear measurements. The
      measurements from both the remote terminal units and the phasor measurement unit
      are subject to quantizations described by a logarithmic quantizer. Attention is
      focused on the design of a recursive filter such that, in the simultaneous
      presence of nonlinear measurements and quantization effects, an upper bound for
      the estimation error covariance is guaranteed and subsequently minimized. Instead
      of using the traditional approximation methods in nonlinear estimation that
      simply ignore the linearization errors, we treat both the linearization and
      quantization errors as norm-bounded uncertainties in the algorithm development so
      as to improve the performance of the estimator. For the power system with such
      kind of introduced uncertainties, a filter is designed in the framework of robust
      recursive estimation, and the developed filter algorithm is tested on the IEEE
      benchmark power system to demonstrate its effectiveness.

PMID- 25576576
TI  - The FRK1 mitogen-activated protein kinase kinase kinase (MAPKKK) from Solanum
      chacoense is involved in embryo sac and pollen development.
AB  - The fertilization-related kinase 1 (ScFRK1), a nuclear-localized mitogen
      activated protein kinase kinase kinase (MAPKKK) from the wild potato species
      Solanum chacoense, belongs to a small group of pMEKKs that do not possess an
      extended N- or C-terminal regulatory domain. Initially selected based on its
      highly specific expression profile following fertilization, in situ expression
      analyses revealed that the ScFRK1 gene is also expressed early on during female
      gametophyte development in the integument and megaspore mother cell and, later,
      in the synergid and egg cells of the embryo sac. ScFRK1 mRNAs are also detected
      in pollen mother cells. Transgenic plants with lower or barely detectable levels
      of ScFRK1 mRNAs lead to the production of small fruits with severely reduced seed
      set, resulting from a concomitant decline in the number of normal embryo sacs
      produced. Megagametogenesis and microgametogenesis were affected, as megaspores
      did not progress beyond the functional megaspore (FG1) stage and the microspore
      collapsed around the first pollen mitosis. As for other mutants that affect
      embryo sac development, pollen tube guidance was severely affected in the ScFRK1
      transgenic lines. Gametophyte to sporophyte communication was also affected, as
      observed from a marked change in the transcriptomic profiles of the sporophytic
      tissues of the ovule. The ScFRK1 MAPKKK is thus involved in a signalling cascade
      that regulates both male and female gamete development. 

PMID- 25576580
TI  - Energy-to-peak state estimation for Markov jump RNNs with time-varying delays via
      nonsynchronous filter with nonstationary mode transitions.
AB  - In this paper, the problem of energy-to-peak state estimation for a class of
      discrete-time Markov jump recurrent neural networks (RNNs) with randomly
      occurring nonlinearities (RONs) and time-varying delays is investigated. A
      practical phenomenon of nonsynchronous jumps between RNNs modes and desired mode
      dependent filters is considered, and a nonstationary mode transition among the
      filters is used to model the nonsynchronous jumps to different degrees that are
      also mode dependent. The RONs are used to model a class of sector-like
      nonlinearities that occur in a probabilistic way according to a Bernoulli
      sequence. The time-varying delays are supposed to be mode dependent and unknown,
      but with known lower and upper bounds a priori. Sufficient conditions on the
      existence of the nonsynchronous filters are obtained such that the filtering
      error system is stochastically stable and achieves a prescribed energy-to-peak
      performance index. Further to the recent study on the class of nonsynchronous
      estimation problem, a monotonicity is observed in obtaining filtering performance
      index, while changing the degree of nonsynchronous jumps. A numerical example is
      presented to verify the theoretical findings. 

PMID- 25576581
TI  - Linear regression-based efficient SVM learning for large-scale classification.
AB  - For large-scale classification tasks, especially in the classification of images,
      additive kernels have shown a state-of-the-art accuracy. However, even with the
      recent development of fast algorithms, learning speed and the ability to handle
      large-scale tasks are still open problems. This paper proposes algorithms for
      large-scale support vector machines (SVM) classification and other tasks using
      additive kernels. First, a linear regression SVM framework for general nonlinear
      kernel is proposed using linear regression to approximate gradient computations
      in the learning process. Second, we propose a power mean SVM (PmSVM) algorithm
      for all additive kernels using nonsymmetric explanatory variable functions. This
      nonsymmetric kernel approximation has advantages over the existing methods: 1) it
      does not require closed-form Fourier transforms and 2) it does not require extra
      training for the approximation either. Compared on benchmark large-scale
      classification data sets with millions of examples or millions of dense feature
      dimensions, PmSVM has achieved the highest learning speed and highest accuracy
      among recent algorithms in most cases. 

PMID- 25576582
TI  - On the role of astroglial syncytia in self-repairing spiking neural networks.
AB  - It has been shown that brain-like self-repair can arise from the interactions
      between neurons and astrocytes where endocannabinoids are synthesized and
      released from active neurons. This retrograde messenger feeds back to local
      synapses directly and indirectly to distant synapses via astrocytes. This
      direct/indirect feedback of the endocannabinoid retrograde messenger results in
      the modulation of the probability of release (PR) at synaptic sites. When
      synapses fail, there is a corresponding falloff in the firing activity of the
      associated neurons, and hence the strength of the direct feedback messenger
      diminishes. This triggers an increase in PR of healthy synapses, due to the
      indirect messenger from other active neurons, which is the catalyst for the
      repair process. In this paper, the repair process is implemented by developing a
      new learning rule that captures the spike-timing-dependent plasticity and
      Bienenstock, Cooper, and Munro learning rules. The rule is activated by the
      increase in PR and results in a potentiation of the weight values, which
      reestablishes the firing activity of neurons. In addition, this self-repairing
      mechanism is extended to network-level repair where astrocyte to astrocyte
      communications are implemented using a linear gap junction model. This
      facilitates the implementation of an astroglial syncytium involving multiple
      astrocytes, which relays the indirect feedback messenger to distant neurons: each
      astrocyte is bidirectionally coupled to neurons. A detailed and comprehensive set
      of results with analysis is presented demonstrating repair at both cellular and
      network levels. 

PMID- 25576583
TI  - Optimal codesign of nonlinear control systems based on a modified policy
      iteration method.
AB  - This brief studies the optimal codesign of nonlinear control systems:
      simultaneous design of physical plants and related optimal control policies.
      Nonlinearity of the optimal codesign problem could come from either a
      nonquadratic cost function or the plant. After formulating the optimal codesign
      into a nonconvex optimization problem, an iterative scheme is proposed in this
      brief by adding an additional step of system-equivalence-based policy improvement
      to the conventional policy iteration. We have proved rigorously that the closed
      loop system performance can be improved after each step of the proposed policy
      iteration scheme, and the convergence to a suboptimal solution is guaranteed. It
      is also shown that under certain conditions, this additional policy improvement
      step can be conducted by solving a quadratic programming problem. The linear
      version of the proposed methodology is addressed in the context of linear
      quadratic regulator. Finally, the effectiveness of the proposed methodology is
      illustrated through the optimal codesign of a load-positioning system. 

PMID- 25576584
TI  - Synchronization of linearly coupled networks with delays via aperiodically
      intermittent pinning control.
AB  - In this paper, we investigate the exponential synchronization problem for
      linearly coupled networks with delay by pinning a simple aperiodically
      intermittent controller. The network topology can be directed. Different from
      previous works, the intermittent control can be aperiodic. Two types of delay are
      considered. The first case is that the delay is time-varying and large, and in
      this case, there is no restriction imposed on the delay and the control (and/or
      rest) width. The other one is that the delay is small enough so that it is less
      than the minimum of control width. Different approaches are provided to
      investigate these two cases, and some criteria are given to realize exponential
      synchronization. Furthermore, by applying the adaptive approach to the second
      model, we establish a general adaptive theory for intermittent control, which can
      be applied not only to networks without time delay, but also to delayed networks,
      regardless of whether the intermittent control is periodic or aperiodic. Finally,
      the numerical simulations are given to verify the validness of the theoretical
      results. 

PMID- 25576586
TI  - Coexistence of ZigBee-Based WBAN and WiFi for Health Telemonitoring Systems.
AB  - The development of telemonitoring via wireless body area networks (WBANs) is an
      evolving direction in personalized medicine and home-based mobile health. A WBAN
      consists of small, intelligent medical sensors which collect physiological
      parameters such as electrocardiogram, electroencephalography, and blood pressure.
      The recorded physiological signals are sent to a coordinator via wireless
      technologies, and are then transmitted to a healthcare monitoring center. One of
      the most widely used wireless technologies in WBANs is ZigBee because it is
      targeted at applications that require a low data rate and long battery life.
      However, ZigBee-based WBANs face severe interference problems in the presence of
      WiFi networks. This problem is caused by the fact that most ZigBee channels
      overlap with WiFi channels, severely affecting the ability of healthcare
      monitoring systems to guarantee reliable delivery of physiological signals. To
      solve this problem, we have developed an algorithm that controls the load in WiFi
      networks to guarantee the delay requirement for physiological signals, especially
      for emergency messages, in environments with coexistence of ZigBee-based WBAN and
      WiFi. Since WiFi applications generate traffic with different delay requirements,
      we focus only on WiFi traffic that does not have stringent timing requirements.
      In this paper, therefore, we propose an adaptive load control algorithm for
      ZigBee-based WBAN/WiFi coexistence environments, with the aim of guaranteeing
      that the delay experienced by ZigBee sensors does not exceed a maximally
      tolerable period of time. Simulation results show that our proposed algorithm
      guarantees the delay performance of ZigBee-based WBANs by mitigating the effects
      of WiFi interference in various scenarios. 

PMID- 25576585
TI  - A Novel Method for Automated Diagnosis of Epilepsy Using Complex-Valued
      Classifiers.
AB  - The study reported herein proposes a new method for the diagnosis of epilepsy
      from electroencephalography (EEG) signals based on complex classifiers. To carry
      out this study, first the features of EEG data are extracted using a dual-tree
      complex wavelet transformation at different levels of granularity to obtain size
      reduction. In subsequent phases, five features (based on statistical measurements
      maximum value, minimum value, arithmetic mean, standard deviation, median value)
      are obtained by using the feature vectors, and are presented as the input
      dimension to the complex-valued neural networks. The evaluation of the proposed
      method is conducted using the k-fold cross-validation methodology, reporting on
      classification accuracy, sensitivity, and specificity. The proposed method is
      tested using a benchmark EEG dataset, and high accuracy rates were obtained. The
      stated results show that the proposed method can be used to design an accurate
      classification system for epilepsy diagnosis. 

PMID- 25576587
TI  - Pose Estimation for General Cameras Using Lines.
AB  - In this paper, we address the problem of pose estimation under the framework of
      generalized camera models. We propose a solution based on the knowledge of the
      coordinates of 3-D straight lines (expressed in the world coordinate frame) and
      their corresponding image pixels. Previous approaches used the knowledge of the
      coordinates of 3-D points (zero dimensional elements) and their corresponding
      images (zero dimensional elements). In this paper, pixels belonging to the image
      of 3-D lines are used. There is no need to establish correspondences between
      pixels and 3-D points. Correspondences are established between 3-D lines and
      their images. There is no need to identify individual pixels. The use of
      correspondences between pixels (that belong to the images of the 3-D lines) and 3
      D lines facilitates the correspondence problem when compared to the use of world
      and image points. This is one of the contributions of this paper. The approach is
      both evaluated and validated using synthetic data and also real images. 

PMID- 25576588
TI  - Fully Connected Cascade Artificial Neural Network Architecture for Attention
      Deficit Hyperactivity Disorder Classification From Functional Magnetic Resonance
      Imaging Data.
AB  - Automated recognition and classification of brain diseases are of tremendous
      value to society. Attention deficit hyperactivity disorder (ADHD) is a diverse
      spectrum disorder whose diagnosis is based on behavior and hence will benefit
      from classification utilizing objective neuroimaging measures. Toward this end,
      an international competition was conducted for classifying ADHD using functional
      magnetic resonance imaging data acquired from multiple sites worldwide. Here, we
      consider the data from this competition as an example to illustrate the utility
      of fully connected cascade (FCC) artificial neural network (ANN) architecture for
      performing classification. We employed various directional and nondirectional
      brain connectivity-based methods to extract discriminative features which gave
      better classification accuracy compared to raw data. Our accuracy for
      distinguishing ADHD from healthy subjects was close to 90% and between the ADHD
      subtypes was close to 95%. Further, we show that, if properly used, FCC ANN
      performs very well compared to other classifiers such as support vector machines
      in terms of accuracy, irrespective of the feature used. Finally, the most
      discriminative connectivity features provided insights about the pathophysiology
      of ADHD and showed reduced and altered connectivity involving the left
      orbitofrontal cortex and various cerebellar regions in ADHD. 

PMID- 25576589
TI  - Reliable Mixed Hinfinity and Passivity-Based Control for Fuzzy Markovian
      Switching Systems With Probabilistic Time Delays and Actuator Failures.
AB  - This paper is concerned with the problem of reliable mixed H infinity and
      passivity-based control for a class of stochastic Takagi-Sugeno (TS) fuzzy
      systems with Markovian switching and probabilistic time varying delays. Different
      from the existing works, the Hinfinity and passivity control problem with
      probabilistic occurrence of time-varying delays and actuator failures is
      considered in a unified framework, which is more general in some practical
      situations. The main aim of this paper is to design a reliable mixed Hinfinity
      and passivity-based controller such that the stochastic TS fuzzy system with
      Markovian switching is stochastically stable with a prescribed mixed Hinfinity
      and passivity performance level gamma > 0 . Based on the Lyapunov-Krasovskii
      functional (LKF) involving lower and upper bound of probabilistic time delay and
      convex combination technique, a new set of delay-dependent sufficient condition
      in terms of linear matrix inequalities (LMIs) is established for obtaining the
      required result. Finally, a numerical example based on the modified truck-trailer
      model is given to demonstrate the effectiveness and applicability of the proposed
      design techniques.

PMID- 25576590
TI  - Content-Based Visual Landmark Search via Multimodal Hypergraph Learning.
AB  - While content-based landmark image search has recently received a lot of
      attention and became a very active domain, it still remains a challenging
      problem. Among the various reasons, high diverse visual content is the most
      significant one. It is common that for the same landmark, images with a wide
      range of visual appearances can be found from different sources and different
      landmarks may share very similar sets of images. As a consequence, it is very
      hard to accurately estimate the similarities between the landmarks purely based
      on single type of visual feature. Moreover, the relationships between landmark
      images can be very complex and how to develop an effective modeling scheme to
      characterize the associations still remains an open question. Motivated by these
      concerns, we propose multimodal hypergraph (MMHG) to characterize the complex
      associations between landmark images. In MMHG, images are modeled as independent
      vertices and hyperedges contain several vertices corresponding to particular
      views. Multiple hypergraphs are firstly constructed independently based on
      different visual modalities to describe the hidden high-order relations from
      different aspects. Then, they are integrated together to involve discriminative
      information from heterogeneous sources. We also propose a novel content-based
      visual landmark search system based on MMHG to facilitate effective search.
      Distinguished from the existing approaches, we design a unified computational
      module to support query-specific combination weight learning. An extensive
      experiment study on a large-scale test collection demonstrates the effectiveness
      of our scheme over state-of-the-art approaches. 

PMID- 25576591
TI  - Optimal Tracking Control of Unknown Discrete-Time Linear Systems Using Input
      Output Measured Data.
AB  - In this paper, an output-feedback solution to the infinite-horizon linear
      quadratic tracking (LQT) problem for unknown discrete-time systems is proposed.
      An augmented system composed of the system dynamics and the reference trajectory
      dynamics is constructed. The state of the augmented system is constructed from a
      limited number of measurements of the past input, output, and reference
      trajectory in the history of the augmented system. A novel Bellman equation is
      developed that evaluates the value function related to a fixed policy by using
      only the input, output, and reference trajectory data from the augmented system.
      By using approximate dynamic programming, a class of reinforcement learning
      methods, the LQT problem is solved online without requiring knowledge of the
      augmented system dynamics only by measuring the input, output, and reference
      trajectory from the augmented system. We develop both policy iteration (PI) and
      value iteration (VI) algorithms that converge to an optimal controller that
      require only measuring the input, output, and reference trajectory data. The
      convergence of the proposed PI and VI algorithms is shown. A simulation example
      is used to verify the effectiveness of the proposed control scheme. 

PMID- 25576592
TI  - Trimming of two major type 1 diabetes driving antigens, GAD65 and IA-2, allows
      for successful expression in Lactococcus lactis.
AB  - Type 1 diabetes (T1D) is a chronic autoimmune disease characterised by excessive
      immune reactions against auto-antigens of pancreatic beta-cells. Restoring auto
      antigen tolerance remains the superior therapeutic strategy. Oral auto-antigen
      administration uses the tolerogenic nature of the gut-associated immune system to
      induce antigen-specific tolerance. However, due to gastric degradation, proper
      mucosal product delivery often imposes a challenge. Recombinant Lactococcus
      lactis have proven to be effective and safe carriers for gastrointestinal
      delivery of therapeutic products: L. lactis secreting diabetes-associated auto
      antigens in combination with interleukin (IL)-10 have demonstrated therapeutic
      efficacy in a well-defined mouse model for T1D. Here, we describe the
      construction of recombinant L. lactis secreting the 65 kDa isoform of glutamic
      acid decarboxylase (GAD65) and tyrosine phosphatase-like protein ICA512 (IA-2),
      two major T1D-related auto-antigens. Attempts to secrete full size human GAD65
      and IA-2 protein by L. lactis were unsuccessful. Trimming of GAD65 and IA-2 was
      investigated to optimise antigen secretion while maintaining sufficient bacterial
      growth. GAD65370-575 and IA-2635-979 showed to be efficiently secreted by
      recombinant L. lactis. Antigen secretion was verified by immunoblotting. Plasmid
      derived GAD65 and IA-2 expression was combined in single strains with human IL-10
      expression, a desired combination to allow tolerance induction. This study
      reports the generation of recombinant L. lactis secreting two major diabetes
      related auto-antigens: human GAD65 and IA-2, by themselves or combined with the
      anti-inflammatory cytokine human IL-10. Prohibitive sequence obstacles hampering
      antigen secretion were resolved by trimming the full size proteins. 

PMID- 25576593
TI  - The history of probiotics: the untold story.
AB  - Probiotic, a word derived from Latin, means 'for life'. A long time before the
      awareness of probiotic microorganisms, fermented products, such as beer, bread,
      wine, kefir, kumis and cheese had been very frequently used for nutritional and
      therapeutic purposes. It is widely believed that fermented products were probably
      found, or better to say, discovered spontaneously. The legend tells that yoghurt
      is most likely resulted from a fermentation process within the animal skin bags
      used for transportation of water and milk in regions with low humidity and high
      temperatures (Middle Asia and Middle East). The history of probiotics goes
      paralel with the evolution of human race and, thanks to the sophisticated
      techniques at the moment, can be traced back to the ancient times, nearly 10,000
      years ago. The aims of this review are to highlight the important events for
      probiotic history, to correct the widely available anonymous misinformation in
      the literature and to remind to the readers important characters in its history. 

PMID- 25576594
TI  - Acupuncture's role in tendinopathy: new possibilities.

PMID- 25576595
TI  - The inducible costimulator augments Tc17 cell responses to self and tumor tissue.
AB  - The inducible costimulator (ICOS) plays a key role in the development of Th17
      cells, but its role in the development and antitumor activity of IL-17-producing
      CD8(+) T cells (Tc17) remains unknown. We found that ICOS costimulation was
      important for the functional maintenance, but not differentiation, of Tc17 cells
      in vitro. Blocking the ICOS pathway using an antagonist mAb or by using recipient
      mice genetically deficient in the ICOS ligand reduced the antitumor activity of
      adoptively transferred Tc17 cells. Conversely, activating Tc17 cells with an ICOS
      agonist in vitro enhanced their capacity to eradicate melanoma and induce
      autoimmune vitiligo when infused into mice. However, ICOS stimulation did not
      augment the antitumor activity of IL-2 expanded T cells. Additional investigation
      revealed that ICOS stimulation not only increased IL-2Ralpha, CXCR3, and IL-23R
      expression on Tc17 cells, but also dampened their expression of suppressive
      molecule CD39. Although Tc17 cells activated with an ICOS agonist cosecreted
      heightened IL-17A, IL-9, and IFN-gamma, their therapeutic effectiveness was
      critically dependent on IFN-gamma production. Depletion of IL-17A and IL-9 had
      little impact on antitumor Tc17 cells activated with an ICOS agonist.
      Collectively, our work reveals that the ICOS pathway potentiates the antitumor
      activity of adoptively transferred Tc17 cells. This work has major implications
      for the design of vaccine, Ab and cell-based therapies for autoimmunity,
      infectious disease, and cancer. 

PMID- 25576596
TI  - Alternatively spliced myeloid differentiation protein-2 inhibits TLR4-mediated
      lung inflammation.
AB  - We previously identified a novel alternatively spliced isoform of human myeloid
      differentiation protein-2 (MD-2s) that competitively inhibits binding of MD-2 to
      TLR4 in vitro. In this study, we investigated the protective role of MD-2s in LPS
      induced acute lung injury by delivering intratracheally an adenovirus construct
      that expressed MD-2s (Ad-MD-2s). After adenovirus-mediated gene transfer, MD-2s
      was strongly expressed in lung epithelial cells and readily detected in
      bronchoalveolar lavage fluid. Compared to adenovirus serotype 5 containing an
      empty vector lacking a transgene control mice, Ad-MD-2s delivery resulted in
      significantly less LPS-induced inflammation in the lungs, including less protein
      leakage, cell recruitment, and expression of proinflammatory cytokines and
      chemokines, such as IL-6, keratinocyte chemoattractant, and MIP-2.
      Bronchoalveolar lavage fluid from Ad-MD-2s mice transferred into lungs of naive
      mice before intratracheal LPS challenge diminished proinflammatory cytokine
      levels. As house dust mite (HDM) sensitization is dependent on TLR4 and HDM Der p
      2, a structural homolog of MD-2, we also investigated the effect of MD-2s on HDM
      induced allergic airway inflammation. Ad-MD-2s given before HDM sensitization
      significantly inhibited subsequent allergic airway inflammation after HDM
      challenge, including reductions in eosinophils, goblet cell hyperplasia, and IL-5
      levels. Our study indicates that the alternatively spliced short isoform of human
      MD-2 could be a potential therapeutic candidate to treat human diseases induced
      or exacerbated by TLR4 signaling, such as Gram-negative bacterial endotoxin
      induced lung injury and HDM-triggered allergic lung inflammation. 

PMID- 25576598
TI  - Interplay Between Transmitted and Acquired HIV Type 1 Drug Resistance: Reasons
      for a Disconnect.

PMID- 25576597
TI  - Defining CD4 T cell memory by the epigenetic landscape of CpG DNA methylation.
AB  - Memory T cells are primed for rapid responses to Ag; however, the molecular
      mechanisms responsible for priming remain incompletely defined. CpG methylation
      in promoters is an epigenetic modification, which regulates gene transcription.
      Using targeted bisulfite sequencing, we examined methylation of 2100 genes
      (56,000 CpGs) mapped by deep sequencing of T cell activation in human naive and
      memory CD4 T cells. Four hundred sixty-six CpGs (132 genes) displayed
      differential methylation between naive and memory cells. Twenty-one genes
      exhibited both differential methylation and gene expression before activation,
      linking promoter DNA methylation states to gene regulation; 6 of 21 genes encode
      proteins closely studied in T cells, whereas 15 genes represent novel targets for
      further study. Eighty-four genes demonstrated differential methylation between
      memory and naive cells that correlated to differential gene expression following
      activation, of which 39 exhibited reduced methylation in memory cells coupled
      with increased gene expression upon activation compared with naive cells. These
      reveal a class of primed genes more rapidly expressed in memory compared with
      naive cells and putatively regulated by DNA methylation. These findings define a
      DNA methylation signature unique to memory CD4 T cells that correlates with
      activation-induced gene expression. 

PMID- 25576599
TI  - Reemergence and amplification of tuberculosis in the Canadian arctic.
AB  - BACKGROUND: Between November 2011 and November 2012, a Canadian village of 933
      persons had 50 culture-positive cases of tuberculosis, with 49 sharing the same
      genotype. METHODS: We performed Illumina-based whole-genome sequencing on
      Mycobacterium tuberculosis isolates from this village, during and before the
      outbreak. Phylogenetic trees were generated using the maximum likelihood method.
      RESULTS: Three distinct genotypes were identified. Strain I (n = 7) was isolated
      in 1991-1996. Strain II (n = 8) was isolated in 1996-2004. Strain III (n = 62)
      first appeared in 2007 and did not arise from strain I or II. Within strain III,
      there were 3 related but distinct clusters: IIIA, IIIB, and IIIC. Between 2007
      and 2010, cluster IIIA predominated (11 of 22 vs 2 of 40; P < .001), whereas in
      2011-2012 clusters IIIB (n = 18) and IIIC (n = 20) predominated over cluster IIIA
      (n = 11). Combined evolutionary and epidemiologic analysis of strain III cases
      revealed that the outbreak in 2011-2012 was the result of >=6 temporally
      staggered events, spanning from 1 reactivation case to a point-source outbreak of
      20 cases. CONCLUSIONS: After the disappearance of 2 strains of M. tuberculosis in
      this village, its reemergence in 2007 was followed by an epidemiologic
      amplification, affecting >5% of the population.

PMID- 25576600
TI  - Assessing the Paradox Between Transmitted and Acquired HIV Type 1 Drug Resistance
      Mutations in the Swiss HIV Cohort Study From 1998 to 2012.
AB  - BACKGROUND: Transmitted human immunodeficiency virus type 1 (HIV) drug resistance
      (TDR) mutations are transmitted from nonresponding patients (defined as patients
      with no initial response to treatment and those with an initial response for whom
      treatment later failed) or from patients who are naive to treatment. Although the
      prevalence of drug resistance in patients who are not responding to treatment has
      declined in developed countries, the prevalence of TDR mutations has not.
      Mechanisms causing this paradox are poorly explored. METHODS: We included
      recently infected, treatment-naive patients with genotypic resistance tests
      performed <= 1 year after infection and before 2013. Potential risk factors for
      TDR mutations were analyzed using logistic regression. The association between
      the prevalence of TDR mutations and population viral load (PVL) among treated
      patients during 1997-2011 was estimated with Poisson regression for all TDR
      mutations and individually for the most frequent resistance mutations against
      each drug class (ie, M184V/L90M/K103N). RESULTS: We included 2421 recently
      infected, treatment-naive patients and 5399 patients with no response to
      treatment. The prevalence of TDR mutations fluctuated considerably over time. Two
      opposing developments could explain these fluctuations: generally continuous
      increases in the prevalence of TDR mutations (odds ratio, 1.13; P = .010),
      punctuated by sharp decreases in the prevalence when new drug classes were
      introduced. Overall, the prevalence of TDR mutations increased with decreasing
      PVL (rate ratio [RR], 0.91 per 1000 decrease in PVL; P = .033). Additionally, we
      observed that the transmitted high-fitness-cost mutation M184V was positively
      associated with the PVL of nonresponding patients carrying M184V (RR, 1.50 per
      100 increase in PVL; P < .001). Such association was absent for K103N (RR, 1.00
      per 100 increase in PVL; P = .99) and negative for L90M (RR, 0.75 per 100
      increase in PVL; P = .022). CONCLUSIONS: Transmission of antiretroviral drug
      resistance is temporarily reduced by the introduction of new drug classes and
      driven by nonresponding and treatment-naive patients. These findings suggest a
      continuous need for new drugs, early detection/treatment of HIV-1 infection.

PMID- 25576601
TI  - Arsenite oxidase also functions as an antimonite oxidase.
AB  - Arsenic and antimony are toxic metalloids and are considered priority
      environmental pollutants by the U.S. Environmental Protection Agency. Significant
      advances have been made in understanding microbe-arsenic interactions and how
      they influence arsenic redox speciation in the environment. However, even the
      most basic features of how and why a microorganism detects and reacts to antimony
      remain poorly understood. Previous work with Agrobacterium tumefaciens strain 5A
      concluded that oxidation of antimonite [Sb(III)] and arsenite [As(III)] required
      different biochemical pathways. Here, we show with in vivo experiments that a
      mutation in aioA [encoding the large subunit of As(III) oxidase] reduces the
      ability to oxidize Sb(III) by approximately one-third relative to the ability of
      the wild type. Further, in vitro studies with the purified As(III) oxidase from
      Rhizobium sp. strain NT-26 (AioA shares 94% amino acid sequence identity with
      AioA of A. tumefaciens) provide direct evidence of Sb(III) oxidation but also
      show a significantly decreased Vmax compared to that of As(III) oxidation. The
      aioBA genes encoding As(III) oxidase are induced by As(III) but not by Sb(III),
      whereas arsR gene expression is induced by both As(III) and Sb(III), suggesting
      that detection and transcriptional responses for As(III) and Sb(III) differ.
      While Sb(III) and As(III) are similar with respect to cellular extrusion (ArsB or
      Acr3) and interaction with ArsR, they differ in the regulatory mechanisms that
      control the expression of genes encoding the different Ars or Aio activities. In
      summary, this study documents an enzymatic basis for microbial Sb(III) oxidation,
      although additional Sb(III) oxidation activity also is apparent in this
      bacterium. 

PMID- 25576602
TI  - Metabolic engineering of an ATP-neutral Embden-Meyerhof-Parnas pathway in
      Corynebacterium glutamicum: growth restoration by an adaptive point mutation in
      NADH dehydrogenase.
AB  - Corynebacterium glutamicum uses the Embden-Meyerhof-Parnas pathway of glycolysis
      and gains 2 mol of ATP per mol of glucose by substrate-level phosphorylation
      (SLP). To engineer glycolysis without net ATP formation by SLP, endogenous
      phosphorylating NAD-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      was replaced by nonphosphorylating NADP-dependent glyceraldehyde-3-phosphate
      dehydrogenase (GapN) from Clostridium acetobutylicum, which irreversibly converts
      glyceraldehyde-3-phosphate (GAP) to 3-phosphoglycerate (3-PG) without generating
      ATP. As shown recently (S. Takeno, R. Murata, R. Kobayashi, S. Mitsuhashi, and M.
      Ikeda, Appl Environ Microbiol 76:7154-7160, 2010,
      http://dx.doi.org/10.1128/AEM.01464-10), this ATP-neutral, NADPH-generating
      glycolytic pathway did not allow for the growth of Corynebacterium glutamicum
      with glucose as the sole carbon source unless hitherto unknown suppressor
      mutations occurred; however, these mutations were not disclosed. In the present
      study, a suppressor mutation was identified, and it was shown that heterologous
      expression of udhA encoding soluble transhydrogenase from Escherichia coli partly
      restored growth, suggesting that growth was inhibited by NADPH accumulation.
      Moreover, genome sequence analysis of second-site suppressor mutants that were
      able to grow faster with glucose revealed a single point mutation in the gene of
      non-proton-pumping NADH:ubiquinone oxidoreductase (NDH-II) leading to the amino
      acid change D213G, which was shared by these suppressor mutants. Since related
      NDH-II enzymes accepting NADPH as the substrate possess asparagine or glutamine
      residues at this position, D213G, D213N, and D213Q variants of C. glutamicum NDH
      II were constructed and were shown to oxidize NADPH in addition to NADH. Taking
      these findings together, ATP-neutral glycolysis by the replacement of endogenous
      NAD-dependent GAPDH with NADP-dependent GapN became possible via oxidation of
      NADPH formed in this pathway by mutant NADPH-accepting NDH-II(D213G) and thus by
      coupling to electron transport phosphorylation (ETP). 

PMID- 25576603
TI  - AmyM, a Novel Maltohexaose-Forming alpha-Amylase from Corallococcus sp. strain
      EGB.
AB  - A novel alpha-amylase, AmyM, was purified from the culture supernatant of
      Corallococcus sp. strain EGB. AmyM is a maltohexaose-forming exoamylase with an
      apparent molecular mass of 43 kDa. Based on the results of matrix-assisted laser
      desorption ionization-time of flight mass spectrometry and peptide mass
      fingerprinting of AmyM and by comparison to the genome sequence of Corallococcus
      coralloides DSM 2259, the AmyM gene was identified and cloned into Escherichia
      coli. amyM encodes a secretory amylase with a predicted signal peptide of 23
      amino acid residues, which showed no significant identity with known and
      functionally verified amylases. amyM was expressed in E. coli BL21(DE3) cells
      with a hexahistidine tag. The signal peptide efficiently induced the secretion of
      mature AmyM in E. coli. Recombinant AmyM (rAmyM) was purified by Ni
      nitrilotriacetic acid (NTA) affinity chromatography, with a specific activity of
      up to 14,000 U/mg. rAmyM was optimally active at 50 degrees C in Tris-HCl buffer
      (50 mM; pH 7.0) and stable at temperatures of <50 degrees C. rAmyM was stable
      over a wide range of pH values (from pH 5.0 to 10.0) and highly tolerant to high
      concentrations of salts, detergents, and various organic solvents. Its activity
      toward starch was independent of calcium ions. The Km and Vmax of recombinant
      AmyM for soluble starch were 6.61 mg ml(-1) and 44,301.5 MUmol min(-1) mg(-1),
      respectively. End product analysis showed that maltohexaose accounted for 59.4%
      of the maltooligosaccharides produced. These characteristics indicate that AmyM
      has great potential in industrial applications. 

PMID- 25576604
TI  - Distinct roles for carbohydrate-binding modules of glycoside hydrolase 10 (GH10)
      and GH11 xylanases from Caldicellulosiruptor sp. strain F32 in thermostability
      and catalytic efficiency.
AB  - Xylanases are crucial for lignocellulosic biomass deconstruction and generally
      contain noncatalytic carbohydrate-binding modules (CBMs) accessing recalcitrant
      polymers. Understanding how multimodular enzymes assemble can benefit protein
      engineering by aiming at accommodating various environmental conditions. Two
      multimodular xylanases, XynA and XynB, which belong to glycoside hydrolase
      families 11 (GH11) and GH10, respectively, have been identified from
      Caldicellulosiruptor sp. strain F32. In this study, both xylanases and their
      truncated mutants were overexpressed in Escherichia coli, purified, and
      characterized. GH11 XynATM1 lacking CBM exhibited a considerable improvement in
      specific activity (215.8 U nmol(-1) versus 94.7 U nmol(-1)) and thermal stability
      (half-life of 48 h versus 5.5 h at 75 degrees C) compared with those of XynA.
      However, GH10 XynB showed higher enzyme activity and thermostability than its
      truncated mutant without CBM. Site-directed mutagenesis of N-terminal amino acids
      resulted in a mutant, XynATM1-M, with 50% residual activity improvement at 75
      degrees C for 48 h, revealing that the disordered region influenced protein
      thermostability negatively. The thermal stability of both xylanases and their
      truncated mutants were consistent with their melting temperature (Tm), which was
      determined by using differential scanning calorimetry. Through homology modeling
      and cross-linking analysis, we demonstrated that for XynB, the resistance against
      thermoinactivation generally was enhanced through improving both domain
      properties and interdomain interactions, whereas for XynA, no interdomain
      interactions were observed. Optimized intramolecular interactions can accelerate
      thermostability, which provided microbes a powerful evolutionary strategy to
      assemble catalysts that are adapted to various ecological conditions. 

PMID- 25576605
TI  - Metabolism of 2-methylpropene (isobutylene) by the aerobic bacterium
      Mycobacterium sp. strain ELW1.
AB  - An aerobic bacterium (Mycobacterium sp. strain ELW1) that utilizes 2
      methylpropene (isobutylene) as a sole source of carbon and energy was isolated
      and characterized. Strain ELW1 grew on 2-methylpropene (growth rate = 0.05 h(-1))
      with a yield of 0.38 mg (dry weight) mg 2-methylpropene(-1). Strain ELW1 also
      grew more slowly on both cis- and trans-2-butene but did not grow on any other C2
      to C5 straight-chain, branched, or chlorinated alkenes tested. Resting 2
      methylpropene-grown cells consumed ethene, propene, and 1-butene without a lag
      phase. Epoxyethane accumulated as the only detected product of ethene oxidation.
      Both alkene consumption and epoxyethane production were fully inhibited in cells
      exposed to 1-octyne, suggesting that alkene oxidation is initiated by an alkyne
      sensitive, epoxide-generating monooxygenase. Kinetic analyses indicated that 1,2
      epoxy-2-methylpropane is rapidly consumed during 2-methylpropene degradation,
      while 2-methyl-2-propen-1-ol is not a significant metabolite of 2-methylpropene
      catabolism. Degradation of 1,2-epoxy-2-methylpropane by 2-methylpropene-grown
      cells led to the accumulation and further degradation of 2-methyl-1,2-propanediol
      and 2-hydroxyisobutyrate, two sequential metabolites previously identified in the
      aerobic microbial metabolism of methyl tert-butyl ether (MTBE) and tert-butyl
      alcohol (TBA). Growth of strain ELW1 on 2-methylpropene, 1,2-epoxy-2
      methylpropane, 2-methyl-1,2-propanediol, and 2-hydroxyisobutyrate was fully
      inhibited when cobalt ions were omitted from the growth medium, while growth on 3
      hydroxybutyrate and other substrates was unaffected by the absence of added
      cobalt ions. Our results suggest that, like aerobic MTBE- and TBA-metabolizing
      bacteria, strain ELW1 utilizes a cobalt/cobalamin-dependent mutase to transform 2
      hydroxyisobutyrate. Our results have been interpreted in terms of their impact on
      our understanding of the microbial metabolism of alkenes and ether oxygenates. 

PMID- 25576606
TI  - A halophilic bacterium inhabiting the warm, CaCl2-rich brine of the perennially
      ice-covered Lake Vanda, McMurdo Dry Valleys, Antarctica.
AB  - Lake Vanda is a perennially ice-covered and stratified lake in the McMurdo Dry
      Valleys, Antarctica. The lake develops a distinct chemocline at about a 50-m
      depth, where the waters transition from cool, oxic, and fresh to warm, sulfidic,
      and hypersaline. The bottom water brine is unique, as the highly chaotropic salts
      CaCl2 and MgCl2 predominate, and CaCl2 levels are the highest of those in any
      known microbial habitat. Enrichment techniques were used to isolate 15 strains of
      heterotrophic bacteria from the Lake Vanda brine. Despite direct supplementation
      of the brine samples with different organic substrates in primary enrichments,
      the same organism, a relative of the halophilic bacterium Halomonas
      (Gammaproteobacteria), was isolated from all depths sampled. The Lake Vanda (VAN)
      strains were obligate aerobes and showed broad pH, salinity, and temperature
      ranges for growth, consistent with the physicochemical properties of the brine.
      VAN strains were halophilic and quite CaCl2 tolerant but did not require CaCl2
      for growth. The fact that only VAN strain-like organisms appeared in our
      enrichments hints that the highly chaotropic nature of the Lake Vanda brine may
      place unusual physiological constraints on the bacterial community that inhabits
      it. 

PMID- 25576607
TI  - Oligopolyphenylenevinylene-conjugated oligoelectrolyte membrane insertion
      molecules selectively disrupt cell envelopes of Gram-positive bacteria.
AB  - The modification of microbial membranes to achieve biotechnological strain
      improvement with exogenous small molecules, such as oligopolyphenylenevinylene
      conjugated oligoelectrolyte (OPV-COE) membrane insertion molecules (MIMs), is an
      emerging biotechnological field. Little is known about the interactions of OPV
      COEs with their target, the bacterial envelope. We studied the toxicity of three
      previously reported OPV-COEs with a selection of Gram-negative and Gram-positive
      organisms and demonstrated that Gram-positive bacteria are more sensitive to OPV
      COEs than Gram-negative bacteria. Transmission electron microscopy demonstrated
      that these MIMs disrupt microbial membranes and that this occurred to a much
      greater degree in Gram-positive organisms. We used a number of mutants to probe
      the nature of MIM interactions with the microbial envelope but were unable to
      align the membrane perturbation effects of these compounds to previously reported
      membrane disruption mechanisms of, for example, cationic antimicrobial peptides.
      Instead, the data support the notion that OPV-COEs disrupt microbial membranes
      through a suspected interaction with diphosphatidylglycerol (DPG), a major
      component of Gram-positive membranes. The integrity of model membranes containing
      elevated amounts of DPG was disrupted to a greater extent by MIMs than those
      prepared from Escherichia coli total lipid extracts alone. 

PMID- 25576608
TI  - Inhibitory effects of C2 to C10 1-alkynes on ammonia oxidation in two
      Nitrososphaera species.
AB  - A previous study showed that ammonia oxidation by the Thaumarchaeota
      Nitrosopumilus maritimus (group 1.1a) was resistant to concentrations of the C8 1
      alkyne, octyne, which completely inhibits activity by ammonia-oxidizing bacteria.
      In this study, the inhibitory effects of octyne and other C2 to C10 1-alkynes
      were evaluated on the nitrite production activity of two pure culture isolates
      from Thaumarchaeota group 1.1b, Nitrososphaera viennensis strain EN76 and
      Nitrososphaera gargensis. Both N. viennensis and N. gargensis were insensitive to
      concentrations of octyne that cause complete and irreversible inactivation of
      nitrite production by ammonia-oxidizing bacteria. However, octyne concentrations
      (>=20 MUM) that did not inhibit N. maritimus partially inhibited nitrite
      production in N. viennensis and N. gargensis in a manner that did not show the
      characteristics of irreversible inactivation. In contrast to previous studies
      with an ammonia-oxidizing bacterium, Nitrosomonas europaea, octyne inhibition of
      N. viennensis was: (i) fully and immediately reversible, (ii) not competitive
      with NH4 (+), and (iii) without effect on the competitive interaction between NH4
      (+) and acetylene. Both N. viennensis and N. gargensis demonstrated the same
      overall trend in regard to 1-alkyne inhibition as previously observed for N.
      maritimus, being highly sensitive to <=C5 alkynes and more resistant to longer
      chain length alkynes. Reproducible differences were observed among N. maritimus,
      N. viennensis, and N. gargensis in regard to the extent of their
      resistance/sensitivity to C6 and C7 1-alkynes, which may indicate differences in
      the ammonia monooxygenase binding and catalytic site(s) among the Thaumarchaeota.

PMID- 25576609
TI  - Genetic determinants of reutericyclin biosynthesis in Lactobacillus reuteri.
AB  - Reutericyclin is a unique antimicrobial tetramic acid produced by some strains of
      Lactobacillus reuteri. This study aimed to identify the genetic determinants of
      reutericyclin biosynthesis. Comparisons of the genomes of reutericyclin-producing
      L. reuteri strains with those of non-reutericyclin-producing strains identified a
      genomic island of 14 open reading frames (ORFs) including genes coding for a
      nonribosomal peptide synthetase (NRPS), a polyketide synthase (PKS), homologues
      of PhlA, PhlB, and PhlC, and putative transport and regulatory proteins. The
      protein encoded by rtcN is composed of a condensation domain, an adenylation
      domain likely specific for d-leucine, and a thiolation domain. rtcK codes for a
      PKS that is composed of a ketosynthase domain, an acyl-carrier protein domain,
      and a thioesterase domain. The products of rtcA, rtcB, and rtcC are homologous to
      the diacetylphloroglucinol-biosynthetic proteins PhlABC and may acetylate the
      tetramic acid moiety produced by RtcN and RtcK, forming reutericyclin. Deletion
      of rtcN or rtcABC in L. reuteri TMW1.656 abrogated reutericyclin production but
      did not affect resistance to reutericyclin. Genes coding for transport and
      regulatory proteins could be deleted only in the reutericyclin-negative L.
      reuteri strain TMW1.656DeltartcN, and these deletions eliminated reutericyclin
      resistance. The genomic analyses suggest that the reutericyclin genomic island
      was horizontally acquired from an unknown source during a unique event. The
      combination of PhlABC homologues with both an NRPS and a PKS has also been
      identified in the lactic acid bacteria Streptococcus mutans and Lactobacillus
      plantarum, suggesting that the genes in these organisms and those in L. reuteri
      share an evolutionary origin. 

PMID- 25576611
TI  - Anoxygenic photosynthesis controls oxygenic photosynthesis in a cyanobacterium
      from a sulfidic spring.
AB  - Before the Earth's complete oxygenation (0.58 to 0.55 billion years [Ga] ago),
      the photic zone of the Proterozoic oceans was probably redox stratified, with a
      slightly aerobic, nutrient-limited upper layer above a light-limited layer that
      tended toward euxinia. In such oceans, cyanobacteria capable of both oxygenic and
      sulfide-driven anoxygenic photosynthesis played a fundamental role in the global
      carbon, oxygen, and sulfur cycle. We have isolated a cyanobacterium,
      Pseudanabaena strain FS39, in which this versatility is still conserved, and we
      show that the transition between the two photosynthetic modes follows a
      surprisingly simple kinetic regulation controlled by this organism's affinity for
      H2S. Specifically, oxygenic photosynthesis is performed in addition to anoxygenic
      photosynthesis only when H2S becomes limiting and its concentration decreases
      below a threshold that increases predictably with the available ambient light.
      The carbon-based growth rates during oxygenic and anoxygenic photosynthesis were
      similar. However, Pseudanabaena FS39 additionally assimilated NO3 (-) during
      anoxygenic photosynthesis. Thus, the transition between anoxygenic and oxygenic
      photosynthesis was accompanied by a shift of the C/N ratio of the total bulk
      biomass. These mechanisms offer new insights into the way in which, despite
      nutrient limitation in the oxic photic zone in the mid-Proterozoic oceans,
      versatile cyanobacteria might have promoted oxygenic photosynthesis and total
      primary productivity, a key step that enabled the complete oxygenation of our
      planet and the subsequent diversification of life. 

PMID- 25576610
TI  - Microbial engineering for aldehyde synthesis.
AB  - Aldehydes are a class of chemicals with many industrial uses. Several aldehydes
      are responsible for flavors and fragrances present in plants, but aldehydes are
      not known to accumulate in most natural microorganisms. In many cases, microbial
      production of aldehydes presents an attractive alternative to extraction from
      plants or chemical synthesis. During the past 2 decades, a variety of aldehyde
      biosynthetic enzymes have undergone detailed characterization. Although metabolic
      pathways that result in alcohol synthesis via aldehyde intermediates were long
      known, only recent investigations in model microbes such as Escherichia coli have
      succeeded in minimizing the rapid endogenous conversion of aldehydes into their
      corresponding alcohols. Such efforts have provided a foundation for microbial
      aldehyde synthesis and broader utilization of aldehydes as intermediates for
      other synthetically challenging biochemical classes. However, aldehyde toxicity
      imposes a practical limit on achievable aldehyde titers and remains an issue of
      academic and commercial interest. In this minireview, we summarize published
      efforts of microbial engineering for aldehyde synthesis, with an emphasis on de
      novo synthesis, engineered aldehyde accumulation in E. coli, and the challenge of
      aldehyde toxicity. 

PMID- 25576612
TI  - Effect of temperature and relative humidity on the survival of foodborne viruses
      during food storage.
AB  - Millions of people suffer from foodborne diseases throughout the world every
      year, and the importance of food safety has grown worldwide in recent years. The
      aim of this study was to investigate the survival of hepatitis A virus (HAV) and
      viral surrogates of human norovirus (HuNoV) (bacteriophage MS2 and murine
      norovirus [MNV]) in food over time. HAV, MNV, and MS2 were inoculated onto either
      the digestive gland of oysters or the surface of fresh peppers, and their
      survival on these food matrices was measured under various temperature (4 degrees
      C, 15 degrees C, 25 degrees C, and 40 degrees C) and relative humidity (RH) (50%
      and 70%) conditions. Inoculated viruses were recovered from food samples and
      quantified by a plaque assay at predetermined time points over 2 weeks (0, 1, 3,
      7, 10, and 14 days). Virus survival was influenced primarily by temperature. On
      peppers at 40 degrees C and at 50% RH, >4- and 6-log reductions of MNV and HAV,
      respectively, occurred within 1 day. All three viruses survived better on
      oysters. In addition, HAV survived better at 70% RH than at 50% RH. The survival
      data for HAV, MS2, and MNV were fit to three different mathematical models
      (linear, Weibull, and biphasic models). Among them, the biphasic model was
      optimum in terms of goodness of fit. The results of this study suggest that major
      foodborne viruses such as HAV and HuNoV can survive over prolonged periods of
      time with a limited reduction in numbers. Because a persistence of foodborne
      virus on contaminated foods was observed, precautionary preventive measures
      should be performed. 

PMID- 25576613
TI  - Piliation of Lactobacillus rhamnosus GG promotes adhesion, phagocytosis, and
      cytokine modulation in macrophages.
AB  - Recently, spaCBA-encoded pili on the cell surface of Lactobacillus rhamnosus GG
      were identified to be key molecules for binding to human intestinal mucus and
      Caco-2 intestinal epithelial cells. Here, we investigated the role of the SpaCBA
      pilus of L. rhamnosus GG in the interaction with macrophages in vitro by
      comparing the wild type with surface mutants. Our results show that SpaCBA pili
      play a significant role in the capacity for adhesion to macrophages and also
      promote bacterial uptake by these phagocytic cells. Interestingly, our data
      suggest that SpaCBA pili also mediate anti-inflammatory effects by induction of
      interleukin-10 (IL-10) mRNA and reduction of interleukin-6 (IL-6) mRNA in a
      murine RAW 264.7 macrophage cell line. These pili appear to mediate these effects
      indirectly by promoting close contact with the macrophages, facilitating the
      exertion of anti-inflammatory effects by other surface molecules via yet unknown
      mechanisms. Blockage of complement receptor 3 (CR3), previously identified to be
      a receptor for streptococcal pili, significantly decreased the uptake of pilus
      expressing strains in RAW 264.7 cells, while the expression of IL-10 and IL-6
      mRNA by these macrophages was not affected by this blocking. On the other hand,
      blockage of Toll-like receptor 2 (TLR2) significantly reduced the expression of
      IL-6 mRNA irrespective of the presence of pili. 

PMID- 25576614
TI  - Comparison of concentration methods for quantitative detection of sewage
      associated viral markers in environmental waters.
AB  - Pathogenic human viruses cause over half of gastroenteritis cases associated with
      recreational water use worldwide. They are relatively difficult to concentrate
      from environmental waters due to typically low concentrations and their small
      size. Although rapid enumeration of viruses by quantitative PCR (qPCR) has the
      potential to greatly improve water quality analysis and risk assessment, the
      upstream steps of capturing and recovering viruses from environmental water
      sources along with removing PCR inhibitors from extracted nucleic acids remain
      formidable barriers to routine use. Here, we compared the efficiency of virus
      recovery for three rapid methods of concentrating two microbial source tracking
      (MST) viral markers human adenoviruses (HAdVs) and polyomaviruses (HPyVs) from
      one liter tap water and river water samples on HA membranes (90 mm in diameter).
      Samples were spiked with raw sewage, and viral adsorption to membranes was
      promoted by acidification (method A) or addition of MgCl2 (methods B and C).
      Viral nucleic acid was extracted directly from membranes (method A), or viruses
      were eluted with NaOH and concentrated by centrifugal ultrafiltration (methods B
      and C). No inhibition of qPCR was observed for samples processed by method A, but
      inhibition occurred in river samples processed by B and C. Recovery efficiencies
      of HAdVs and HPyVs were ~10-fold greater for method A (31 to 78%) than for
      methods B and C (2.4 to 12%). Further analysis of membranes from method B
      revealed that the majority of viruses were not eluted from the membrane,
      resulting in poor recovery. The modification of the originally published method A
      to include a larger diameter membrane and a nucleic acid extraction kit that
      could accommodate the membrane resulted in a rapid virus concentration method
      with good recovery and lack of inhibitory compounds. The frequently used strategy
      of viral absorption with added cations (Mg(2+)) and elution with acid were
      inefficient and more prone to inhibition, and will result in underestimation of
      the prevalence and concentrations of HAdVs and HPyVs markers in environmental
      waters. 

PMID- 25576615
TI  - Efficient metabolic exchange and electron transfer within a syntrophic
      trichloroethene-degrading coculture of Dehalococcoides mccartyi 195 and
      Syntrophomonas wolfei.
AB  - Dehalococcoides mccartyi 195 (strain 195) and Syntrophomonas wolfei were grown in
      a sustainable syntrophic coculture using butyrate as an electron donor and carbon
      source and trichloroethene (TCE) as an electron acceptor. The maximum
      dechlorination rate (9.9 +/- 0.1 MUmol day(-1)) and cell yield [(1.1 +/- 0.3) *
      10(8) cells MUmol(-1) Cl(-)] of strain 195 maintained in coculture were,
      respectively, 2.6 and 1.6 times higher than those measured in the pure culture.
      The strain 195 cell concentration was about 16 times higher than that of S.
      wolfei in the coculture. Aqueous H2 concentrations ranged from 24 to 180 nM
      during dechlorination and increased to 350 +/- 20 nM when TCE was depleted,
      resulting in cessation of butyrate fermentation by S. wolfei with a theoretical
      Gibbs free energy of -13.7 +/- 0.2 kJ mol(-1). Carbon monoxide in the coculture
      was around 0.06 MUmol per bottle, which was lower than that observed for strain
      195 in isolation. The minimum H2 threshold value for TCE dechlorination by strain
      195 in the coculture was 0.6 +/- 0.1 nM. Cell aggregates during syntrophic growth
      were observed by scanning electron microscopy. The interspecies distances to
      achieve H2 fluxes required to support the measured dechlorination rates were
      predicted using Fick's law and demonstrated the need for aggregation. Filamentous
      appendages and extracellular polymeric substance (EPS)-like structures were
      present in the intercellular spaces. The transcriptome of strain 195 during
      exponential growth in the coculture indicated increased ATP-binding cassette
      transporter activities compared to the pure culture, while the membrane-bound
      energy metabolism related genes were expressed at stable levels. 

PMID- 25576616
TI  - Resistant microbial cooccurrence patterns inferred by network topology.
AB  - Although complex cooccurrence patterns have been described for microbes in
      natural communities, these patterns have scarcely been interpreted in the context
      of ecosystem functioning and stability. Here we constructed networks from species
      cooccurrences between pairs of microorganisms which were extracted from five
      individual aquatic time series, including a dystrophic and a eutrophic lake as
      well as an open ocean site. The resulting networks exhibited higher clustering
      coefficients, shorter path lengths, and higher average node degrees and levels of
      betweenness than those of random networks. Moreover, simulations demonstrated
      that taxa with a large number of cooccurrences and placement at convergence
      positions in the network, so-called "hubs" and "bottlenecks," confer resistance
      against random removal of "taxa." Accordingly, we refer to cooccurrences at
      convergence positions as system-relevant interdependencies, as they, like hubs
      and bottlenecks, determine network topology. These topology features of the
      cooccurrence networks point toward microbial community dynamics being resistant
      over time and thus could provide indicators for the state of ecosystem stability.

PMID- 25576617
TI  - Improvement of LysM-mediated surface display of designed ankyrin repeat proteins
      (DARPins) in recombinant and nonrecombinant strains of Lactococcus lactis and
      Lactobacillus Species.
AB  - Safety and probiotic properties make lactic acid bacteria (LAB) attractive hosts
      for surface display of heterologous proteins. Protein display on nonrecombinant
      microorganisms is preferred for therapeutic and food applications due to
      regulatory requirements. We displayed two designed ankyrin repeat proteins
      (DARPins), each possessing affinity for the Fc region of human IgG, on the
      surface of Lactococcus lactis by fusing them to the Usp45 secretion signal and to
      the peptidoglycan-binding C terminus of AcmA, containing lysine motif (LysM)
      repeats. Growth medium containing a secreted fusion protein was used to test its
      heterologous binding to 10 strains of species of the genus Lactobacillus, using
      flow cytometry, whole-cell enzyme-linked immunosorbent assay (ELISA), and
      fluorescence microscopy. The fusion proteins bound to the surfaces of all
      lactobacilli; however, binding to the majority of bacteria was only 2- to 5-fold
      stronger than that of the control. Lactobacillus salivarius ATCC 11741
      demonstrated exceptionally strong binding (32- to 55-fold higher than that of the
      control) and may therefore be an attractive host for nonrecombinant surface
      display. Genomic comparison of the species indicated the exopolysaccharides of
      Lb. salivarius as a possible reason for the difference. Additionally, a 15-fold
      concentration-dependent increase in nonrecombinant surface display on L. lactis
      was demonstrated by growing bacteria with sublethal concentrations of the
      antibiotics chloramphenicol and erythromycin. Nonrecombinant surface display on
      LAB, based on LysM repeats, was optimized by selecting Lactobacillus salivarius
      ATCC 11741 as the optimal host and by introducing antibiotics as additives for
      increasing surface display on L. lactis. Additionally, effective display of
      DARPins on the surfaces of nonrecombinant LAB has opened up several new
      therapeutic possibilities. 

PMID- 25576618
TI  - L-lactate production from biodiesel-derived crude glycerol by metabolically
      engineered Enterococcus faecalis: cytotoxic evaluation of biodiesel waste and
      development of a glycerol-inducible gene expression system.
AB  - Biodiesel waste is a by-product of the biodiesel production process that contains
      a large amount of crude glycerol. To reuse the crude glycerol, a novel
      bioconversion process using Enterococcus faecalis was developed through
      physiological studies. The E. faecalis strain W11 could use biodiesel waste as a
      carbon source, although cell growth was significantly inhibited by the oil
      component in the biodiesel waste, which decreased the cellular NADH/NAD(+) ratio
      and then induced oxidative stress to cells. When W11 was cultured with glycerol,
      the maximum culture density (optical density at 600 nm [OD600]) under anaerobic
      conditions was decreased 8-fold by the oil component compared with that under
      aerobic conditions. Furthermore, W11 cultured with dihydroxyacetone (DHA) could
      show slight or no growth in the presence of the oil component with or without
      oxygen. These results indicated that the DHA kinase reaction in the glycerol
      metabolic pathway was sensitive to the oil component as an oxidant. The lactate
      dehydrogenase (Ldh) activity of W11 during anaerobic glycerol metabolism was 4.1
      fold lower than that during aerobic glycerol metabolism, which was one of the
      causes of low l-lactate productivity. The E. faecalis pflB gene disruptant
      (Deltapfl mutant) expressing the ldhL1LP gene produced 300 mM l-lactate from
      glycerol/crude glycerol with a yield of >99% within 48 h and reached a maximum
      productivity of 18 mM h(-1) (1.6 g liter(-1) h(-1)). Thus, our study demonstrates
      that metabolically engineered E. faecalis can convert crude glycerol to l-lactate
      at high conversion efficiency and provides critical information on the recycling
      process for biodiesel waste. 

PMID- 25576619
TI  - Temporal stability of the microbial community in sewage-polluted seawater exposed
      to natural sunlight cycles and marine microbiota.
AB  - Billions of gallons of untreated wastewater enter the coastal ocean each year.
      Once sewage microorganisms are in the marine environment, they are exposed to
      environmental stressors, such as sunlight and predation. Previous research has
      investigated the fate of individual sewage microorganisms in seawater but not the
      entire sewage microbial community. The present study used next-generation
      sequencing (NGS) to examine how the microbial community in sewage-impacted
      seawater changes over 48 h when exposed to natural sunlight cycles and marine
      microbiota. We compared the results from microcosms composed of unfiltered
      seawater (containing naturally occurring marine microbiota) and filtered seawater
      (containing no marine microbiota) to investigate the effect of marine microbiota.
      We also compared the results from microcosms that were exposed to natural
      sunlight cycles with those from microcosms kept in the dark to investigate the
      effect of sunlight. The microbial community composition and the relative
      abundance of operational taxonomic units (OTUs) changed over 48 h in all
      microcosms. Exposure to sunlight had a significant effect on both community
      composition and OTU abundance. The effect of marine microbiota, however, was
      minimal. The proportion of sewage-derived microorganisms present in the
      microcosms decreased rapidly within 48 h, and the decrease was the most
      pronounced in the presence of both sunlight and marine microbiota, where the
      proportion decreased from 85% to 3% of the total microbial community. The results
      from this study demonstrate the strong effect that sunlight has on microbial
      community composition, as measured by NGS, and the importance of considering
      temporal effects in future applications of NGS to identify microbial pollution
      sources. 

PMID- 25576620
TI  - Physical covering for control of Escherichia coli O157:H7 and Salmonella spp. in
      static and windrow composting processes.
AB  - This study investigated the effect of a 30-cm covering of finished compost (FC)
      on survival of Escherichia coli O157:H7 and Salmonella spp. in active static and
      windrow composting systems. Feedstocks inoculated with E. coli O157:H7 (7.41 log
      CFU/g) and Salmonella (6.46 log CFU/g) were placed in biosentry tubes (7.5-cm
      diameter, 30-cm height) at three locations: (i and ii) two opposing sides at the
      interface between the FC cover layer (where present) and the feedstock material
      (each positioned approximately 10 cm below the pile's surface) and (iii) an
      internal location (top) (approximately 30 cm below the surface). On specific
      sampling days, surviving populations of inoculated E. coli O157:H7 and
      Salmonella, generic E. coli, and coliforms in compost samples were determined.
      Salmonella spp. were reduced significantly within 24 h in windrow piles and were
      below the detection limit after 3 and 7 days at internal locations of windrow and
      static piles containing FC covering, respectively. Likewise, E. coli O157:H7 was
      undetectable after 1 day in windrow piles covered with finished compost. Use of
      FC as a covering layer significantly increased the number of days that
      temperatures in the windrows remained >=55 degrees C at all locations and in
      static piles at internal locations. These time-temperature exposures resulted in
      rapid reduction of inoculated pathogens, and the rate of bacterial reduction was
      rapid in windrow piles. The sample location significantly influenced the survival
      of these pathogens at internal locations compared to that at interface locations
      of piles. Finished compost covering of compost piles aids in the reduction of
      pathogens during the composting process. 

PMID- 25576624
TI  - Catheter-Based Radiofrequency Renal Denervation: Location Effects on Renal
      Norepinephrine.
AB  - BACKGROUND: Clinical studies indicate that blood pressure (BP)-lowering effects
      of radiofrequency (RF) renal denervation (RD) are sustained for up to 2 years,
      although a recent clinical trial failed to find a major effect compared to sham
      treatment. In most previous studies, the efficacy of RD has not been assessed.
      The current study determined whether RD in different regions of the renal artery
      causes different degrees of RD as assessed with renal norepinephrine (NE) levels.
      METHODS AND RESULTS: Unilateral RD was performed on 14 pigs divided into 3
      groups: RD near the ostium, in the main renal artery near the bifurcation, and in
      extrarenal branches of the renal artery. After 2 weeks post-RD, the pigs were
      euthanized, renal cortex tissue was collected for NE measurement, and renal
      arteries were prepared for histological analysis. Renal NE decreased by 12% with
      RD at the ostium, 45% with RD near the bifurcation in the main renal artery, and
      74% when RD was performed in extrarenal artery branches. The number of renal
      nerves was greatest in extrarenal branches and in the main artery compared to the
      ostium and the average distance from the lumen was greatest for nerves at the
      ostium and least at the branches. CONCLUSIONS: RF RD lowers renal NE more
      significantly when performed in branches of the renal artery closer to the
      kidney. Increased efficacy of RF RD in extrarenal arterial branches may be due to
      the greater number of nerves in close proximity to the artery lumen in the
      branches.

PMID- 25576626
TI  - Defective autophagy in vascular smooth muscle cells alters contractility and Ca2+
      homeostasis in mice.
AB  - Autophagy is an evolutionary preserved process that prevents the accumulation of
      unwanted cytosolic material through the formation of autophagosomes. Although
      autophagy has been extensively studied to understand its function in normal
      physiology, the role of vascular smooth muscle (SM) cell (VSMC) autophagy in
      Ca(2+) mobilization and contraction remains poorly understood. Recent evidence
      shows that autophagy is involved in controlling contractile function and Ca(2+)
      homeostasis in certain cell types. Therefore, autophagy might also regulate
      contractile capacity and Ca(2+)-mobilizing pathways in VSMCs. Contractility
      (organ chambers) and Ca(2+) homeostasis (myograph) were investigated in aortic
      segments of 3.5-mo-old mice containing a SM cell-specific deletion of autophagy
      related 7 (Atg7; Atg7(fl/fl) SM22alpha-Cre(+) mice) and in segments of
      corresponding control mice (Atg7(+/+) SM22alpha-Cre(+)). Our results indicate
      that voltage-gated Ca(2+) channels (VGCCs) of Atg7(fl/fl) SM22alpha-Cre(+) VSMCs
      were more sensitive to depolarization, independent of changes in resting membrane
      potential. Contractions elicited with K(+) (50 mM) or the VGCC agonist BAY K8644
      (100 nM) were significantly higher due to increased VGCC expression and activity.
      Interestingly, the sarcoplasmic reticulum of Atg7(fl/fl) SM22alpha-Cre(+) VSMCs
      was enlarged, which, combined with increased sarco(endo)plasmic reticulum Ca(2+)
      ATPase 2 expression and higher store-operated Ca(2+) entry, promoted inositol
      1,4,5-trisphosphate-mediated contractions of Atg7(fl/fl) SM22alpha-Cre(+)
      segments and maximized the Ca(2+) storing capacity of the sarcoplasmic reticulum.
      Moreover, decreased plasma membrane Ca(2+)-ATPase expression in Atg7(fl/fl)
      SM22alpha-Cre(+) VSMCs hampered Ca(2+) extrusion to the extracellular
      environment. Overall, our study indicates that defective autophagy in VSMCs leads
      to an imbalance between Ca(2+) release/influx and Ca(2+) reuptake/extrusion,
      resulting in higher basal Ca(2+) concentrations and significant effects on
      vascular reactivity. 

PMID- 25576625
TI  - Efficacy of prophylactic flavan-3-ol in permanent focal ischemia in 12-mo-old
      mice.
AB  - The consumption of flavan-3-ol-containing foods, including (-)-epicatechin (EC),
      has been linked to lower incidence of cardiovascular disease and stroke. We
      previously demonstrated nuclear transcription factor erythroid 2p45-related
      factor-2 (Nrf2) -dependent EC efficacy in reducing stroke-induced deficits in 2
      mo-old mice; yet stroke is primarily a disease of the elderly. Because
      neuroinflammation, oxidative stress, and vascular dysfunction are hallmarks of
      aging, we tested whether Nrf2 mediates EC efficacy in aging mice through
      modulation of glial responses and blood brain barrier permeability. First, we
      compared anastomosis in naive wild-type and C57BL/6 Nrf2(-/-) mice to identify
      potential differences in cerebrovascular architecture. Data showed no significant
      differences in the number of anastomoses or mean intersection points, indicating
      similar gross vascular physiology. To assess efficacy and mechanisms of
      protection, wild-type or Nrf2(-/-) mice were administered the minimum effective
      EC dose established in our previous studies before the permanent distal middle
      cerebral artery occlusion. Similar to previous results with young mice, 12-mo-old
      wild types also showed significant reductions in infarct volume (41.01 +/-
      29.57%) and improved performance in removing adhesive tape relative to vehicle
      treated controls, whereas a trend toward protection was observed in Nrf2(-/-).
      However, EC did not reduce immunoreactivity for the microglia/macrophage marker
      anti-ionized calcium-binding adapter molecule 1, suggesting that dampened
      activation/recruitment did not account for EC protection. Furthermore, there were
      no differences in mouse IgG extravasation or spontaneous hemorrhage between EC
      treated groups. These data demonstrate that EC protection occurs independent of
      microglia/macrophage modulation or blood brain barrier preservation, suggesting
      that the glial cell responses in young mice are compensatory to another, and
      potentially novel, protective mechanism. 

PMID- 25576627
TI  - Ca2+ entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance.
AB  - Ubiquitously expressed Trpm2 channel limits oxidative stress and preserves
      mitochondrial function. We first demonstrated that intracellular Ca(2+)
      concentration increase after Trpm2 activation was due to direct Ca(2+) influx and
      not indirectly via reverse Na(+)/Ca(2+) exchange. To elucidate whether Ca(2+)
      entry via Trpm2 is required to maintain cellular bioenergetics, we injected
      adenovirus expressing green fluorescent protein (GFP), wild-type (WT) Trpm2, and
      loss-of-function (E960D) Trpm2 mutant into left ventricles of global Trpm2
      knockout (gKO) or WT hearts. Five days post-injection, gKO-GFP heart slices had
      higher reactive oxygen species (ROS) levels but lower oxygen consumption rate
      (OCR) than WT-GFP heart slices. Trpm2 but not E960D decreased ROS and restored
      OCR in gKO hearts back to normal levels. In gKO myocytes expressing Trpm2 or its
      mutants, Trpm2 but not E960D reduced the elevated mitochondrial superoxide (O2(.
      )) levels in gKO myocytes. After hypoxia-reoxygenation (H/R), Trpm2 but not E906D
      or P1018L (inactivates Trpm2 current) lowered O2(.-) levels in gKO myocytes and
      only in the presence of extracellular Ca(2+), indicating sustained Ca(2+) entry
      is necessary for Trpm2-mediated preservation of mitochondrial function. After
      ischemic-reperfusion (I/R), cardiac-specific Trpm2 KO hearts exhibited lower
      maximal first time derivative of LV pressure rise (+dP/dt) than WT hearts in
      vivo. After doxorubicin treatment, Trpm2 KO mice had worse survival and lower
      +dP/dt. We conclude 1) cardiac Trpm2-mediated Ca(2+) influx is necessary to
      maintain mitochondrial function and protect against H/R injury; 2) Ca(2+) influx
      via cardiac Trpm2 confers protection against H/R and I/R injury by reducing
      mitochondrial oxidants; and 3) Trpm2 confers protection in doxorubicin
      cardiomyopathy.

PMID- 25576628
TI  - Brain-derived neurotrophic factor modulates angiotensin signaling in the
      hypothalamus to increase blood pressure in rats.
AB  - Brain-derived neurotrophic factor (BDNF) expression increases in the
      paraventricular nucleus of the hypothalamus (PVN) in response to hypertensive
      stimuli including stress and hyperosmolarity. However, it is unclear whether BDNF
      in the PVN contributes to increases in blood pressure (BP). We tested the
      hypothesis that increased BDNF levels within the PVN would elevate baseline BP
      and heart rate (HR) and cardiovascular stress responses by altering central
      angiotensin signaling. BP was recorded using radiotelemetry in male Sprague
      Dawley rats after bilateral PVN injections of adeno-associated viral vectors
      expressing green fluorescent protein (GFP) or myc epitope-tagged BDNF fusion
      protein. Cardiovascular responses to acute stress were evaluated 3 to 4 wk after
      injections. Additional GFP and BDNF-treated animals were equipped with osmotic
      pumps for intracerebroventricular infusion of saline or the angiotensin type-1
      receptor (AT1R) inhibitor losartan (15 MUg.0.5 MUl(-1).h(-1)). BDNF treatment
      significantly increased baseline BP (121 +/- 3 mmHg vs. 99 +/- 2 mmHg in GFP), HR
      (394 +/- 9 beats/min vs. 314 +/- 4 beats/min in GFP), and sympathetic tone
      indicated by HR- and BP-variability analysis and adrenomedullary tyrosine
      hydroxylase protein expression. In contrast, body weight and BP elevations to
      acute stressors decreased. BDNF upregulated AT1R mRNA by ~80% and downregulated
      Mas receptor mRNA by ~50% in the PVN, and losartan infusion partially inhibited
      weight loss and increases in BP and HR in BDNF-treated animals without any effect
      in GFP rats. Our results demonstrate that BDNF overexpression in the PVN results
      in sympathoexcitation, BP and HR elevations, and weight loss that are mediated,
      at least in part, by modulating angiotensin signaling in the PVN. 

PMID- 25576632
TI  - Impact of tDCS on cerebral autoregulation in aging and in patients with
      cerebrovascular diseases.

PMID- 25576629
TI  - Passive leg movement and nitric oxide-mediated vascular function: the impact of
      age.
AB  - In young healthy men, passive leg movement (PLM) elicits a robust nitric oxide
      (NO)-dependent increase in leg blood flow (LBF), thus providing a novel approach
      to assess NO-mediated vascular function. While the magnitude of the LBF response
      to PLM is markedly reduced with age, the role of NO in this attenuated response
      in the elderly is unknown. Therefore, this study sought to determine the
      contribution of NO in the PLM-induced LBF with age. Fourteen male subjects (7
      young, 24 +/- 1 yr; and 7 old, 75 +/- 3 yr) underwent PLM with and without NO
      synthase (NOS) inhibition achieved by intra-arterial infusion of N(G)-monomethyl
      L-arginine (L-NMMA). LBF was determined second-by-second by Doppler ultrasound,
      and central hemodynamics were measured by finger photoplethysmography. NOS
      inhibition blunted the PLM-induced peak increase in LBF in the young (control:
      668 +/- 106; L-NMMA: 431 +/- 95 Deltaml/min; P = 0.03) but had no effect in the
      old (control: 266 +/- 98; L-NMMA: 251 +/- 92 Deltaml/min; P = 0.59). Likewise,
      the magnitude of the reduction in the overall (i.e., area under the curve) PLM
      induced LBF response to NOS inhibition was less in the old (LBF: -31 +/- 18 ml)
      than the young (LBF: -129 +/- 21 ml; P < 0.01). These findings suggest that the
      age-associated reduction in PLM-induced LBF in the elderly is primarily due to a
      reduced contribution to vasodilation from NO and therefore support the use of PLM
      as a novel approach to assess NO-mediated vascular function across the lifespan.

PMID- 25576633
TI  - MRI biomarkers in mild traumatic brain injury.

PMID- 25576634
TI  - Susceptibility-weighted MRI in mild traumatic brain injury.
AB  - OBJECTIVE: To compare the frequency of microbleeds identified by susceptibility
      weighted MRI (SWMRI) in patients with mild traumatic brain injury (mTBI) and
      normal controls, and correlate these findings with neuropsychological tests.
      METHODS: Research ethics committee approval and patient written informed consents
      were obtained. One hundred eleven patients with mTBI without parenchymal
      hemorrhage on CT and conventional MRI received SWMRI as well as a digit span and
      continuous performance test. One hundred eleven healthy volunteers without
      history of traumatic brain injury were enrolled as the control group and received
      conventional MRI with additional SWMRI study. We analyzed the number and location
      of microbleeds in both groups. RESULTS: Twenty-six patients with mTBI and 12
      control subjects presented microbleeds on SWMRI (p = 0.0197). Sixty microbleeds
      were found in 26 patients with mTBI and 15 microbleeds in 12 control subjects.
      The mTBI group showed notably more microbleeds in the cortex/subcortical region
      (52 microbleeds, 86.7%, vs 3 microbleeds, 20%; p < 0.0001). Conversely, the
      control group showed more microbleeds in the central brain (9 microbleeds, 60%,
      vs 3 microbleeds, 5%; p < 0.0001). There was no statistical difference in number
      of microbleeds in the cerebellum and brainstem (p = 0.2598 and p = 0.4932,
      respectively). Patients with mTBI who had detected microbleeds had lower digit
      span scores than the patients with negative SWMRI findings (p = 0.017).
      CONCLUSION: Presence of mTBI-related microbleeds showed a neuropsychological
      defect on short-term memory function, indicating that the presence of microbleeds
      could be a possible severity biomarker for mTBI. Addition of the SWMRI technique
      to the MRI protocol for patients with mTBI is recommended.

PMID- 25576635
TI  - Seeing big nerves in small children.

PMID- 25576636
TI  - Peripheral nerve ultrasound in pediatric Charcot-Marie-Tooth disease type 1A.
AB  - OBJECTIVE: To investigate differences in nerve cross-sectional area (CSA) as
      measured by peripheral nerve ultrasound in children with Charcot-Marie-Tooth
      disease type 1A (CMT1A) compared to healthy controls. METHODS: This was a cross
      sectional, matched, case-control study. CSA of the median, ulnar, tibial, and
      sural nerves was measured by peripheral nerve ultrasound. The mean difference in
      CSA between children with CMT1A and controls at each nerve site was determined.
      The relationship between nerve CSA and age/body metrics, and between nerve CSA
      and neurologic disability in CMT1A, was also evaluated. RESULTS: Twenty-nine
      children with CMT1A and 29 age- and sex-matched controls were enrolled. Nerve CSA
      was significantly increased in children with CMT1A compared to controls (1.9- to
      3.5-fold increase, p < 0.001). The increase in nerve CSA with age was
      disproportionately greater in those with CMT1A. Nerve CSA showed a strong
      positive linear correlation with age, height, and weight in both the CMT1A and
      control groups. Disease severity correlated with both nerve CSA and age.
      CONCLUSIONS: Children with CMT1A have significantly increased nerve CSA compared
      to controls, and the increase in nerve CSA with age is disproportionately greater
      in CMT1A, suggesting ongoing nerve hypertrophy throughout childhood. Nerve CSA
      correlates with neurologic disability. These findings demonstrate the utility of
      peripheral nerve ultrasound as a diagnostic tool in pediatric neuropathies, and
      as an outcome measure in natural history studies and clinical trials in CMT1A.
      CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that
      measurement of nerve CSA by peripheral nerve ultrasound accurately identifies
      patients with CMT1A.

PMID- 25576637
TI  - Vascular safety of brain plasticity induction via transcranial direct currents.

PMID- 25576638
TI  - Macroautophagic cargo sequestration assays.
AB  - Macroautophagy, the process responsible for bulk sequestration and lysosomal
      degradation of cytoplasm, is often monitored by means of the autophagy-related
      marker protein LC3. This protein is linked to the phagophoric membrane by
      lipidation during the final steps of phagophore assembly, and it remains
      associated with autophagic organelles until it is degraded in the lysosomes. The
      transfer of LC3 from cytosol to membranes and organelles can be measured by
      immunoblotting or immunofluorescence microscopy, but these assays provide no
      information about functional macroautophagic activity, i.e., whether the
      phagophores are actually engaged in the sequestration of cytoplasmic cargo and
      enclosing this cargo into sealed autophagosomes. Moreover, accumulating evidence
      suggest that macroautophagy can proceed independently of LC3. There is therefore
      a need for alternative methods, preferably effective cargo sequestration assays,
      which can monitor actual macroautophagic activity. Here, we provide an overview
      of various approaches that have been used over the last four decades to measure
      macroautophagic sequestration activity in mammalian cells. Particular emphasis is
      given to the so-called "LDH sequestration assay", which measures the transfer of
      the autophagic cargo marker enzyme LDH (lactate dehydrogenase) from the cytosol
      to autophagic vacuoles. The LDH sequestration assay was originally developed to
      measure macroautophagic activity in primary rat hepatocytes. Subsequently, it has
      found use in several other cell types, and in this article we demonstrate a
      further validation and simplification of the method, and show that it is
      applicable to several cell lines that are commonly used to study autophagy. 

PMID- 25576639
TI  - Testosterone differs between suicide attempters and community controls in men and
      women of China.
AB  - OBJECTIVE: To understand how physiological markers of men and women characterize
      the differences in suicide attempt, we hypothesize that attempted suicides have
      higher level of testosterone than their non-suicidal counterparts, which should
      be true of both men and women. METHODS: In Shandong Province of China, 245 rural
      suicide attempters aged 16-50years were consecutively recruited from October 1,
      2009 to March 31, 2011. They were compared with 245 age and gender matched
      community controls. Blood sample was extracted at the time of interview for both
      patients and controls, and the plasma testosterone level was tested for
      comparisons. RESULTS: The testosterone level was significantly higher for male
      suicide attempters than for their community counterparts, with the OR of 1.211
      (95%CI: 1.055-1.391), even when some other factors were adjusted, such as
      education years, family SES, marital status, coping skills, impulsivity, and
      psychiatric disorders. There was also a tendency that high testosterone level was
      related to female suicide attempt, with the OR being 1.209 (95%CI: 0.719-2.031).
      CONCLUSIONS: Testosterone, as a form of physiological marking, is somewhat
      another predictor of attempted suicide. Besides other factors, it might be the
      testosterone, not gender, which explains the suicide risks and the gender ratio
      of the rates. The lack of sample size limited this current study to establish a
      significant and positive relationship between testosterone and suicide risk in
      women as found in men.

PMID- 25576640
TI  - Sweet taste threshold for sucrose inversely correlates with depression symptoms
      in female college students in the luteal phase.
AB  - Influences of depression symptoms on the sweet taste threshold were investigated
      in healthy college students (30 males and 40 females). Depression symptoms were
      scored by SDS (Self-Rating Depression Scale), and anxiety levels by STAI (State-
      and Trait-Anxiety Inventory). Recognition thresholds for sucrose were determined.
      In female students, the menstrual phase on the day of the experiment was self
      reported. Depression symptoms, anxiety levels, and the recognition threshold for
      sucrose were not different among the 3 groups, i.e. males, females in the
      follicular phase, and females in the luteal phase. Depression symptoms were
      positively correlated with state and trait anxiety in all groups. The sweet taste
      threshold was inversely correlated with depression symptoms (r=-0.472, p=0.031)
      and trait anxiety (r=-0.506, p=0.019) in females in the luteal phase. In males as
      well as females in the follicular phase, however, no correlation between sweet
      taste threshold and depression was found. The results show that the recognition
      threshold for sucrose reduces with increased depression in females with a higher
      anxiety trait, but only in the luteal phase. It is hypothesized that brain
      regions, which spatially overlap and are responsible for both aversive emotions
      and gustatory processing, are susceptible to periodic changes in gonadal hormones
      due to the menstrual cycle. 

PMID- 25576641
TI  - Characterization of insulin-loaded liposome using column-switching HPLC.
AB  - We evaluated the drug-encapsulation state of insulin (INS)-loaded liposome using
      a novel column-switching HPLC system that can automatically separate unloaded
      drug from encapsulated drug by hydrophobic interaction. When the INS-loaded
      liposome was dispersed in water (pH 7.4), the encapsulation efficiency (EE)
      obtained by the column-switching HPLC system was consistent with that obtained by
      a conventional ultracentrifugation method. However, the INS-loaded liposome
      dispersed in 0.1% acetic acid (pH 3.3) showed disagreement between the EEs
      obtained by both methods. Considering the results of particle size, zeta
      potential, and transmission electron microscope (TEM) observations, we
      hypothesized that the column-switching HPLC method was able to distinguish INS
      adsorbed onto the liposome surface from the encapsulated INS, although an
      ultracentrifugation method precipitated the adsorbed INS onto the liposome
      surface along with the encapsulated INS. Therefore, the novel column-switching
      HPLC system may be a more accurate and useful technique for characterization and
      optimization of the INS-loaded liposome formulation. 

PMID- 25576642
TI  - Effectiveness of dry needling for myofascial trigger points associated with neck
      and shoulder pain: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate current evidence of the effectiveness of dry needling of
      myofascial trigger points (MTrPs) associated with neck and shoulder pain. DATA
      SOURCES: PubMed, EBSCO, Physiotherapy Evidence Database, ScienceDirect, The
      Cochrane Library, ClinicalKey, Wanfang Data Chinese database, China Knowledge
      Resource Integrated Database, Chinese Chongqing VIP Information, and SpringerLink
      databases were searched from database inception to January 2014. STUDY SELECTION:
      Randomized controlled trials were performed to determine whether dry needling was
      used as the main treatment and whether pain intensity was included as an outcome.
      Participants were diagnosed with MTrPs associated with neck and shoulder pain.
      DATA EXTRACTION: Two reviewers independently screened the articles, scored
      methodological quality, and extracted data. The results of the study of pain
      intensity were extracted in the form of mean and SD data. Twenty randomized
      controlled trials involving 839 patients were identified for meta-analysis. DATA
      SYNTHESIS: Meta-analyses were performed using RevMan version 5.2 and Stata
      version 12.0. The results suggested that compared with control/sham, dry needling
      of MTrPs was effective in the short term (immediately to 3 days) (standardized
      mean difference [SMD]=-1.91; 95% confidence interval [CI], -3.10 to -.73; P=.002)
      and medium term (SMD=-1.07; 95% CI, -1.87 to -.27; P=.009); however, wet needling
      (including lidocaine) was superior to dry needling in relieving MTrP pain in the
      medium term (SMD=1.69; 95% CI, .40-2.98; P=.01). Other therapies (including
      physiotherapy) were more effective than dry needling in treating MTrP pain in the
      medium term (9-28d) (SMD=.62; 95% CI, .02-1.21; P=.04). CONCLUSIONS: Dry needling
      can be recommended for relieving MTrP pain in neck and shoulders in the short and
      medium term, but wet needling is found to be more effective than dry needling in
      relieving MTrP pain in neck and shoulders in the medium term.

PMID- 25576643
TI  - Identifying posttraumatic amnesia in individuals with a Glasgow Coma Scale of 15
      after mild traumatic brain injury.
AB  - OBJECTIVE: To examine the utility of the Abbreviated Westmead Post-traumatic
      Amnesia Scale, which includes the Glasgow Coma Scale (GCS) and 3 picture cards
      used to measure amnesia, in identifying the presence or absence of posttraumatic
      amnesia in individuals with mild traumatic brain injury (mTBI). DESIGN:
      Prospective study using data from the Abbreviated Westmead Post-traumatic Amnesia
      Scale. SETTING: Trauma hospital. PARTICIPANTS: Individuals with possible mTBI who
      presented between April and September 2011 (N=252; age range, 18-65y; mean age,
      37.4+/-13.9y; 77% men). INTERVENTION: Administration of the Abbreviated Westmead
      Post-traumatic Amnesia Scale. MAIN OUTCOME MEASURES: GCS and Abbreviated Westmead
      Post-traumatic Amnesia Scale pass/fail rates. RESULTS: Of the individuals, 169
      (mean age, 35.1+/-13.6y; 77% men) received the scale. A pass/fail performance was
      achieved a median 121 minutes (interquartile range, 89-205min) after triage. Of
      the 45 who failed, 31 (69%) had a GCS score of 15. The likelihood of failing was
      associated with being older (odds ratio [OR], 1.03; 95% confidence interval [CI],
      1.02-1.06; P<.05), having consumed alcohol (OR, 3.09; 95% CI, 1.42-6.74; P<.01),
      and the scale being administered closer to the time of the injury (OR, 0.99; 95%
      CI, 0.99-1.00; P<.05). Nineteen (42%) of those who failed had consumed alcohol,
      11 had a GCS score of 15, and 8 had a GCS score of 14. CONCLUSIONS: A GCS score
      of 15 does not always signify return to normative cognitive function. Individuals
      with a GCS score of 15 who are acutely cognitively impaired are at risk of not
      being accurately identified. The addition of an amnesia score to the GCS in the
      Abbreviated Westmead Post-traumatic Amnesia Scale will assist in making a
      diagnosis of mTBI.

PMID- 25576645
TI  - Investigation of negative BOLD responses in human brain through NIRS technique. A
      visual stimulation study.
AB  - Despite negative blood oxygenation level dependent (BOLD) responses to visual
      stimuli have recently gained considerable interest, the explanation for their
      underlying neuronal and vascular mechanisms is still controversial. In the
      present study, a multimodal experimental approach is presented to shed light on
      the negative BOLD phenomenon in the human brain. In particular, information from
      functional magnetic resonance imaging (fMRI) and near infrared spectroscopy
      (NIRS) was integrated to confirm and gain insight into the phenomenon of negative
      BOLD responses (NBRs) to unpatterned intermittent photic stimulation (IPS) in
      healthy subjects. Eight healthy subjects participated in the study. Consistent
      findings emerged from the activation analysis of fMRI and NIRS data and the
      comparison of BOLD and hemoglobin responses at the single channel level showed
      that NBRs are related to a decrease in oxyhemoglobin (HbO) combined with a lower
      increase in deoxyhemoglobin (HHb), corresponding to a decrease in total
      hemoglobin (THb) and estimated cerebral blood volume (CBV). The HbO and HHb
      variations were significant in at least one channel in six subjects out of eight
      (p<0.05). The NIRS technique allowed obtaining valuable information on the
      vascular determinants of the NBRs, since the discrimination between HbO, HHb and
      THb information provided a more comprehensive view of the negative BOLD
      phenomenon. The within and between subject heterogeneous BOLD-Hb temporal
      relations pave the way to further investigations into the neurovascular
      properties of NBRs. 

PMID- 25576646
TI  - Language-motor interference reflected in MEG beta oscillations.
AB  - The involvement of the brain's motor system in action-related language processing
      can lead to overt interference with simultaneous action execution. The aim of the
      current study was to find evidence for this behavioural interference effect and
      to investigate its neurophysiological correlates using oscillatory MEG analysis.
      Subjects performed a semantic decision task on single action verbs, describing
      actions executed with the hands or the feet, and abstract verbs. Right hand
      button press responses were given for concrete verbs only. Therefore, longer
      response latencies for hand compared to foot verbs should reflect interference.
      We found interference effects to depend on verb imageability: overall response
      latencies for hand verbs did not differ significantly from foot verbs. However,
      imageability interacted with effector: while response latencies to hand and foot
      verbs with low imageability were equally fast, those for highly imageable hand
      verbs were longer than for highly imageable foot verbs. The difference is
      reflected in motor-related MEG beta band power suppression, which was weaker for
      highly imageable hand verbs compared with highly imageable foot verbs. This
      provides a putative neuronal mechanism for language-motor interference where the
      involvement of cortical hand motor areas in hand verb processing interacts with
      the typical beta suppression seen before movements. We found that the
      facilitatory effect of higher imageability on action verb processing time is
      perturbed when verb and motor response relate to the same body part. Importantly,
      this effect is accompanied by neurophysiological effects in beta band
      oscillations. The attenuated power suppression around the time of movement,
      reflecting decreased cortical excitability, seems to result from motor simulation
      during action-related language processing. This is in line with embodied
      cognition theories. 

PMID- 25576644
TI  - cis-Acting RNA elements in the hepatitis C virus RNA genome.
AB  - Hepatitis C virus (HCV) infection is a rapidly increasing global health problem
      with an estimated 170 million people infected worldwide. HCV is a hepatotropic,
      positive-sense RNA virus of the family Flaviviridae. As a positive-sense RNA
      virus, the HCV genome itself must serve as a template for translation,
      replication and packaging. The viral RNA must therefore be a dynamic structure
      that is able to readily accommodate structural changes to expose different
      regions of the genome to viral and cellular proteins to carry out the HCV life
      cycle. The ~ 9600 nucleotide viral genome contains a single long open reading
      frame flanked by 5' and 3' non-coding regions that contain cis-acting RNA
      elements important for viral translation, replication and stability. Additional
      cis-acting RNA elements have also been identified in the coding sequences as well
      as in the 3' end of the negative-strand replicative intermediate. Herein, we
      provide an overview of the importance of these cis-acting RNA elements in the HCV
      life cycle.

PMID- 25576647
TI  - Impulse control in the dorsolateral prefrontal cortex counteracts post-diet
      weight regain in obesity.
AB  - A variety of studies suggest that efficient treatments to induce short-term
      dietary success in obesity exist. However, sustained maintenance of reduced
      weight is rare as a large proportion of patients start to regain weight when
      treatment is discontinued. Thus, from a clinical perspective, it would be
      desirable to identify factors that counteract post-diet weight regain across
      longer time-scales. To address this question, we extended our previous work on
      neural impulse control mechanisms of short-term dietary success in obesity and
      now investigated the mechanisms counteracting long-term weight regain after a
      diet. Specifically, we measured neural impulse control during a delay discounting
      task with fMRI at two time points, i.e. the beginning ('T0') and the end ('T12')
      of a one-year follow-up interval after a 12-week diet. Then, we tested whether
      activity in the dorsolateral prefrontal cortex (DLPFC) at T0 and whether activity
      changes across the follow-up period (T0-T12) are linked to success in weight
      maintenance. The analyses conducted show that control-related DLPFC activity at
      T0 was coupled to the degree of success in weight maintenance. Consistently, also
      behavioral measures of control were linked to the degree of success in
      maintenance. A direct comparison of neural and behavioral control parameters for
      prognostic weight change modeling revealed that neural signals were more
      informative. Taken together, neural impulse control in the DLPFC measured with
      fMRI directly after a diet predicts real-world diet success in obese patients
      across extended time periods. 

PMID- 25576649
TI  - Automation of ALK gene rearrangement testing with fluorescence in situ
      hybridization (FISH): a feasibility study.
AB  - In the past several years we have observed a significant increase in our
      understanding of molecular mechanisms that drive lung cancer. Specifically in the
      non-small cell lung cancer sub-types, ALK gene rearrangements represent a sub
      group of tumors that are targetable by the tyrosine kinase inhibitor Crizotinib,
      resulting in significant reductions in tumor burden. Phase II and III clinical
      trials were performed using an ALK break-apart FISH probe kit, making FISH the
      gold standard for identifying ALK rearrangements in patients. FISH is often
      considered a labor and cost intensive molecular technique, and in this study we
      aimed to demonstrate feasibility for automation of ALK FISH testing, to improve
      laboratory workflow and ease of testing. This involved automation of the pre
      treatment steps of the ALK assay using various protocols on the VP 2000
      instrument, and facilitating automated scanning of the fluorescent FISH specimens
      for simplified enumeration on various backend scanning and analysis systems. The
      results indicated that ALK FISH can be automated. Significantly, both the
      Ikoniscope and BioView system of automated FISH scanning and analysis systems
      provided a robust analysis algorithm to define ALK rearrangements. In addition,
      the BioView system facilitated consultation of difficult cases via the internet. 

PMID- 25576650
TI  - Acquiring visual information for locomotion by older adults: a systematic review.
AB  - Developments in technology have facilitated quantitative examination of gaze
      behavior in relation to locomotion. The objective of this systematic review is to
      provide a critical evaluation of available evidence and to explore the role of
      gaze behavior among older adults during different forms of locomotion. Database
      searches were conducted to identify research papers that met the inclusion
      criteria of (1) study variables that included direct measurement of gaze and at
      least one form of locomotion, (2) participants who were older adults aged 60
      years and above, and (3) reporting original research. Twenty-five papers related
      to walking on a straight path and turning (n=4), stair navigation (n=3), target
      negotiation and obstacle circumvention (n=13) and perturbation-evoked sudden loss
      of balance (n=5) were identified for the final quality assessment. The reviewed
      articles were found to have acceptable quality, with scores ranging from 47.06%
      to 94.12%. Overall, the current literature suggests that differences in gaze
      behavior during locomotion appear to change in late adulthood, especially with
      respect to transfer of gaze to and from a target, saccade-step latency, fixation
      durations on targets and viewing patterns. These changes appear to be
      particularly pronounced for older adults with high risk of falling and impaired
      executive functioning. 

PMID- 25576648
TI  - Dissecting the mechanism of colorectal tumorigenesis based on RNA-sequencing
      data.
AB  - OBJECTIVE: This study aimed to identify the differentially expressed genes
      (DEGs), mutated genes and fusion genes in colorectal cancer. MATERIALS AND
      METHODS: RNA-sequencing data (ID: SRP009386) from cancerous, paracancerous non
      tumor and distant normal tissue from one Chinese patient with stage III
      colorectal cancer were downloaded from Sequence Read Archive. Quality control was
      checked using FastQC, followed by sequence alignment against the hg19 reference
      genome using TopHat v1.3.3. The expression levels were quantified using
      Cufflinks, followed by DEGs screening using NOISeq. Enrichment analysis was
      performed using DAVID. Transcription factors were screened using TRANSFA. Mutated
      loci were identified using SAMTools and VCFTools. Gene fusion events were
      detected by TopHat-fusion. RESULTS: In total 2440, 1887 and 834 DEGs were
      respectively detected in cancerous vs. normal tissue, cancerous vs. paracancerous
      tissue and paracancerous vs. normal tissue. The up-regulated genes from cancerous
      and paracancerous tissue compared with normal tissue were enriched in
      "extracellular matrix receptor interaction" and "focal adhesion pathway" as well
      as some biological processes except for "negative regulation of programmed cell
      death" uniquely presenting in cancer. Dysregulated transcription factors
      including SOX4, BCL6, CEBPB and MSX2 were enriched in the unique biological
      process. Trp53 was identified with one mutated locus 7577142 (C -> T) on
      chromosome 17. BCL6 also experienced missense mutation. Additionally, COL1A1
      PPP2R2C and EXPH5-COL1A2 were observed fusion genes in cancer tissue.
      CONCLUSIONS: The unique biological process in cancer tissue may be the cause for
      colorectal carcinogenesis. The screened transcription factors, mutated genes and
      fusion genes may contribute to the progression of colorectal cancer.

PMID- 25576652
TI  - Growth performance and feed conversion efficiency of three edible mealworm
      species (Coleoptera: Tenebrionidae) on diets composed of organic by-products.
AB  - Insects receive increasing attention as an alternative protein-rich food source
      for humans. Producing edible insects on diets composed of organic by-products
      could increase sustainability. In addition, insect growth rate and body
      composition, and hence nutritional quality, can be altered by diet. Three edible
      mealworm species Tenebrio molitor L., Zophobas atratus Fab. and Alphitobius
      diaperinus Panzer were grown on diets composed of organic by-products originating
      from beer brewing, bread/cookie baking, potato processing and bioethanol
      production. Experimental diets differed with respect to protein and starch
      content. Larval growth and survival was monitored. Moreover, effects of dietary
      composition on feed conversion efficiency and mealworm crude protein and fatty
      acid profile were assessed. Diet affected mealworm development and feed
      conversion efficiency such that diets high in yeast-derived protein appear
      favourable, compared to diets used by commercial breeders, with respect to
      shortening larval development time, reducing mortality and increasing weight
      gain. Diet also affected the chemical composition of mealworms. Larval protein
      content was stable on diets that differed 2-3-fold in protein content, whereas
      dietary fat did have an effect on larval fat content and fatty acid profile.
      However, larval fatty acid profile did not necessarily follow the same trend as
      dietary fatty acid composition. Diets that allowed for fast larval growth and low
      mortality in this study led to a comparable or less favourable n6/n3 fatty acid
      ratio compared to control diets used by commercial breeders. In conclusion, the
      mealworm species used in this study can be grown successfully on diets composed
      of organic by-products. Diet composition did not influence larval protein
      content, but did alter larval fat composition to a certain extent. 

PMID- 25576651
TI  - Lifelong brain health is a lifelong challenge: from evolutionary principles to
      empirical evidence.
AB  - Although the human brain is exceptional in size and information processing
      capabilities, it is similar to other mammals with regard to the factors that
      promote its optimal performance. Three such factors are the challenges of
      physical exercise, food deprivation/fasting, and social/intellectual engagement.
      Because it evolved, in part, for success in seeking and acquiring food, the brain
      functions best when the individual is hungry and physically active, as typified
      by the hungry lion stalking and chasing its prey. Indeed, studies of animal
      models and human subjects demonstrate robust beneficial effects of regular
      exercise and intermittent energy restriction/fasting on cognitive function and
      mood, particularly in the contexts of aging and associated neurodegenerative
      disorders. Unfortunately, the agricultural revolution and the invention of effort
      sparing technologies have resulted in a dramatic reduction or elimination of
      vigorous exercise and fasting, leaving only intellectual challenges to bolster
      brain function. In addition to disengaging beneficial adaptive responses in the
      brain, sedentary overindulgent lifestyles promote obesity, diabetes and
      cardiovascular disease, all of which may increase the risk of cognitive
      impairment and Alzheimer's disease. It is therefore important to embrace the
      reality of the requirements for exercise, intermittent fasting and critical
      thinking for optimal brain health throughout life, and to recognize the dire
      consequences for our aging population of failing to implement such brain-healthy
      lifestyles. 

PMID- 25576654
TI  - Removal of ethylene from air stream by adsorption and plasma-catalytic oxidation
      using silver-based bimetallic catalysts supported on zeolite.
AB  - Dynamic adsorption of ethylene on 13X zeolite-supported Ag and Ag-M(x)O(y) (M:
      Co, Cu, Mn, and Fe), and plasma-catalytic oxidation of the adsorbed ethylene were
      investigated. The experimental results showed that the incorporation of Ag into
      zeolite afforded a marked enhancement in the adsorptivity for ethylene. The
      addition of transition metal oxides was found to have a positive influence on the
      ethylene adsorption, except Fe(x)O(y). The presence of the additional metal
      oxides, however, appeared to somewhat interrupt the diffusion of ozone into the
      zeolite micro-pores, leading to a decrease in the plasma-catalytic oxidation
      efficiency of the ethylene adsorbed there. Among the second additional metal
      oxides, Fe(x)O(y) was able to reduce the emission of ozone during the plasma
      catalytic oxidation stage while keeping a high effectiveness for the oxidative
      removal of the adsorbed ethylene. The periodical treatment consisting of
      adsorption followed by plasma-catalytic oxidation may be a promising energy
      efficient ethylene abatement method.

PMID- 25576653
TI  - Annotation and expression analysis of cuticular proteins from the tobacco
      hornworm, Manduca sexta.
AB  - The insect cuticle is a unique material that covers the exterior of the animal as
      well as lining the foregut, hindgut, and tracheae. It offers protection from
      predators and desiccation, defines body shape, and serves as an attachment site
      for internal organs and muscle. It has demonstrated remarkable variations in
      hardness, flexibility and elasticity, all the while being light weight, which
      allows for ease of movement and flight. It is composed primarily of chitin,
      proteins, catecholamines, and lipids. Proteomic analyses of cuticle from
      different life stages and species of insects has allowed for a more detailed
      examination of the protein content and how it relates to cuticle mechanical
      properties. It is now recognized that several groups of cuticular proteins exist
      and that they can be classified according to conserved amino acid sequence
      motifs. We have annotated the genome of the tobacco hornworm, Manduca sexta, for
      genes that encode putative cuticular proteins that belong to seven different
      groups: proteins with a Rebers and Riddiford motif (CPR), proteins analogous to
      peritrophins (CPAP), proteins with a tweedle motif (CPT), proteins with a 44
      amino acid motif (CPF), proteins that are CPF-like (CPFL), proteins with an 18
      amino acid motif (18 aa), and proteins with two to three copies of a C-X5-C motif
      (CPCFC). In total we annotated 248 genes, of which 207 belong to the CPR family,
      the most for any insect genome annotated to date. Additionally, we discovered new
      members of the CPAP family and determined that orthologous genes are present in
      other insects. We established orthology between the M. sexta and Bombyx mori
      genes and identified duplication events that occurred after separation of the two
      species. Finally, we utilized 52 RNAseq libraries to ascertain gene expression
      profiles that revealed commonalities and differences between different tissues
      and developmental stages. 

PMID- 25576655
TI  - Rapid and convergent evolution in the glioblastoma multiforme genome.
AB  - Determining which mutations drive tumor progression is a defining question in
      cancer genomics. We analyzed sequence evolution in Glioblastoma multiforme (GBM)
      by computing the number of parallel mutations and by estimating omega=dN/dS, a
      measure of the strength and direction of selection. The omega values of almost
      all 7617 mutated genes in GBM are much higher than in germline genes. We
      identified only 21 genes under significant positive selection in GBM, as well as
      29 genes under significant purifying selection, including several zinc finger
      proteins. Therefore, most of the high omega values in the GBM genome are due to
      weaker purifying selection rather than positive selection. We also found multiple
      recurrent mutations in GBM, several of which are associated with patient survival
      time. Our results suggest that convergence and neutral evolution play a
      significant role in GBM, and that sites with recurrent mutations can serve as
      molecular diagnostics of the clinical course of GBM tumors. 

PMID- 25576656
TI  - Towards quantitative electrostatic potential mapping of working semiconductor
      devices using off-axis electron holography.
AB  - Pronounced improvements in the understanding of semiconductor device performance
      are expected if electrostatic potential distributions can be measured
      quantitatively and reliably under working conditions with sufficient sensitivity
      and spatial resolution. Here, we employ off-axis electron holography to
      characterize an electrically-biased Si p-n junction by measuring its
      electrostatic potential, electric field and charge density distributions under
      working conditions. A comparison between experimental electron holographic phase
      images and images obtained using three-dimensional electrostatic potential
      simulations highlights several remaining challenges to quantitative analysis. Our
      results illustrate how the determination of reliable potential distributions from
      phase images of electrically biased devices requires electrostatic fringing
      fields, surface charges, specimen preparation damage and the effects of limited
      spatial resolution to be taken into account. 

PMID- 25576657
TI  - Immunoadjuvant effect of diethylcarbamazine in experimental filariasis.
AB  - Lymphatic filariasis caused by tissue dwelling nematodes is endemic in 73
      countries and drugs have been administered to control or stop the infection.
      Resurgence of the infection after mass drug administration necessitates the study
      of several parasite antigens or adjuvants for vaccine developments. In this
      study, diethylcarbamazine (DEC) was evaluated for its efficacy as adjuvant
      against the filarial parasite; Brugia malayi microfilariae (mf) by combining with
      the Escherichia coli expressed recombinant BmShp-1 protein. Shp-1 is one of the
      sheath proteins expressed by adult female and microfilarial stage of the filarial
      parasite. Hence, immunoprophylactic efficacy of Shp-1 using DEC and alum
      adjuvants was compared in BALB/c mice model by an in situ micropore chamber
      method. Shp-1 antibody titre was high when the mice were immunized with Shp-1
      along with DEC and they exhibited balanced Th1/Th2 profile. DEC also induced
      significantly high T-cell proliferation (P<0.001) when stimulated with Shp-1
      compared to alum. Significantly high percentage protection against B. malayi
      microfilariae was observed in Shp-1+DEC immunized mice groups (P<0.05) and hence
      it is concluded that the need of repeated drug administration can be controlled
      when there is a possibility of developing protective immunity in the host against
      mf by vaccination. 

PMID- 25576658
TI  - IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in
      activated microglia cells.
AB  - The development of agents that can modulate microglial activation has been
      suggested as one potential strategy for the treatment or prevention of
      neurodegenerative diseases. Among these agents, resveratrol, with its anti
      inflammatory action, has been described to have neuroprotective effects. In this
      paper we demonstrate that in LPS-stimulated microglia resveratrol pretreatment
      reduced, in a dose-dependent manner, pro-inflammatory cytokines IL-1beta, TNF
      alpha and IL-6 mRNA expression and increased the release of anti-inflammatory
      interleukin (IL)-10. Moreover, resveratrol pretreatment up-regulated the
      phosphorylated forms of JAK1 and STAT3, as well as suppressor of cytokine
      signaling (SOCS)3 protein expression in LPS activated cells, demonstrating that
      the JAK-STAT signaling pathway is involved in the anti-inflammatory effect
      exerted by resveratrol. By supplementing the cultures with an IL-10 neutralizing
      antibody (IL-10NA) we obtained the opposite effect. Taken together, these data
      allow us to conclude that the LPS-induced pro-inflammatory response in microglial
      cells can be markedly reduced by resveratrol, through IL-10 dependent up
      regulation of SOCS3, requiring the JAK-STAT signaling pathway. 

PMID- 25576659
TI  - Lipoxin A4 attenuates endothelial dysfunction during experimental cerebral
      malaria.
AB  - A breakdown of the brain-blood barrier (BBB) due to endothelial dysfunction is a
      primary feature of cerebral malaria (CM). Lipoxins (LX) are specialized pro
      resolving mediators that attenuate endothelial dysfunction in different vascular
      beds. It has already been shown that LXA4 prolonged Plasmodium berghei-infected
      mice survival by a mechanism that depends on inhibiting IL-12 production and
      CD8(+)IFN-gamma(+) T cells in brain tissue; however, the effects of this
      treatment on endothelial dysfunction induced during experimental cerebral malaria
      (ECM) remains to be elucidated. Herein, we investigate the role of LXA4 on
      endothelial dysfunction during ECM. The treatment of P. berghei-infected mice
      with LXA4 prevented BBB breakdown and ameliorated behavioral symptoms but did not
      modulate TNF-alpha production. In addition, microcirculation analysis showed that
      treatment with LXA4 significantly increased functional capillary density in
      brains of P. berghei-infected C57BL/6 mice. Furthermore, histological analyses of
      brain sections demonstrated that exogenous LXA4 reduced capillary congestion that
      was accompanied by reduced ICAM-1 expression in the brain tissue. In agreement,
      LXA4 treatment of endothelial cells stimulated by Plasmodium berghei (Pb)- or
      Plasmodium falciparum (Pf)-parasitized red blood cells (RBCs) inhibited ICAM-1
      expression. Additionally, LXA4 treatment restored the expression of HO-1 that is
      reduced during ECM. As well, LXA4 treatment inhibits PbRBC and PfRBC adhesion to
      endothelial cells that was reversed by the use of an HO-1 inhibitor (ZnPPIX). Our
      results demonstrate for the first time that LXA4 ameliorates endothelial
      dysfunction during ECM by modulating ICAM-1 and HO-1 expression in brain tissue. 

PMID- 25576660
TI  - Automated flow cytometric analysis across large numbers of samples and cell
      types.
AB  - Multi-parametric flow cytometry is a key technology for characterization of
      immune cell phenotypes. However, robust high-dimensional post-analytic strategies
      for automated data analysis in large numbers of donors are still lacking. Here,
      we report a computational pipeline, called FlowGM, which minimizes operator
      input, is insensitive to compensation settings, and can be adapted to different
      analytic panels. A Gaussian Mixture Model (GMM)-based approach was utilized for
      initial clustering, with the number of clusters determined using Bayesian
      Information Criterion. Meta-clustering in a reference donor permitted automated
      identification of 24 cell types across four panels. Cluster labels were
      integrated into FCS files, thus permitting comparisons to manual gating. Cell
      numbers and coefficient of variation (CV) were similar between FlowGM and
      conventional gating for lymphocyte populations, but notably FlowGM provided
      improved discrimination of "hard-to-gate" monocyte and dendritic cell (DC)
      subsets. FlowGM thus provides rapid high-dimensional analysis of cell phenotypes
      and is amenable to cohort studies. 

PMID- 25576661
TI  - Epigenetic control of autoimmune diseases: from bench to bedside.
AB  - Genome-wide association studies have revealed several genes predisposing to
      autoimmunity, however, concordance rates in monozygotic twins are significantly
      below 50% for several autoimmune diseases. The limited presence of a strong
      genetic association only in some patients supports that other non-genetic
      mechanisms are active in these pathologies. Epigenetic modifications such as DNA
      methylation, histone modification, and microRNA signaling regulate gene
      expression and are sensitive to external stimuli and they might be as bridging
      between genetic and environmental factors. Some evidence has highlighted the
      involvement of epigenetic alterations in the pathogenesis of various autoimmune
      diseases giving rise to great expectations among clinicians and researchers. The
      direct role of these alterations in the initiation/progression of autoimmune
      diseases is still unclear. The knowledge in depth of these pathogenic and
      epigenetic mechanisms will increase the possibility of the control and/or
      prevention of autoimmune diseases through the use of drugs that target epigenetic
      pathways. Moreover, we could use epigenetic-related biomarkers to follow this
      complicated framework (for example H3K4me3 and miRNA-155 are among those proposed
      biomarkers). This article reviews current understanding of the epigenetic
      involvement in the field of autoimmune diseases especially in systemic lupus
      erythematosus, rheumatoid arthritis, sclerosis multiple and type 1 diabetes. 

PMID- 25576662
TI  - Fusobacterium nucleatum: a commensal-turned pathogen.
AB  - Fusobacterium nucleatum is an anaerobic oral commensal and a periodontal pathogen
      associated with a wide spectrum of human diseases. This article reviews its
      implication in adverse pregnancy outcomes (chorioamnionitis, preterm birth,
      stillbirth, neonatal sepsis, preeclampsia), GI disorders (colorectal cancer,
      inflammatory bowel disease, appendicitis), cardiovascular disease, rheumatoid
      arthritis, respiratory tract infections, Lemierre's syndrome and Alzheimer's
      disease. The virulence mechanisms involved in the diseases are discussed, with
      emphasis on its colonization, systemic dissemination, and induction of host
      inflammatory and tumorigenic responses. The FadA adhesin/invasin conserved in F.
      nucleatum is a key virulence factor and a potential diagnostic marker for F.
      nucleatum-associated diseases. 

PMID- 25576664
TI  - Parent feeding interactions and practices during childhood cancer treatment. A
      qualitative investigation.
AB  - In the general population it is evident that parent feeding practices can
      directly shape a child's life long dietary intake. Young children undergoing
      childhood cancer treatment may experience feeding difficulties and limited food
      intake, due to the inherent side effects of their anti-cancer treatment. What is
      not clear is how these treatment side effects are influencing the parent-child
      feeding relationship during anti-cancer treatment. This retrospective qualitative
      study collected telephone based interview data from 38 parents of childhood
      cancer patients who had recently completed cancer treatment (child's mean age:
      6.98 years). Parents described a range of treatment side effects that impacted on
      their child's ability to eat, often resulting in weight loss. Sixty-one percent
      of parents (n = 23) reported high levels of stress in regard to their child's
      eating and weight loss during treatment. Parents reported stress, feelings of
      helplessness, and conflict and/or tension between parent and the child during
      feeding/eating interactions. Parents described using both positive and negative
      feeding practices, such as: pressuring their child to eat, threatening the
      insertion of a nasogastric feeding tube, encouraging the child to eat and
      providing home cooked meals in hospital. Results indicated that parent stress may
      lead to the use of coping strategies such as positive or negative feeding
      practices to entice their child to eat during cancer treatment. Future research
      is recommended to determine the implication of parent feeding practice on the
      long term diet quality and food preferences of childhood cancer survivors. 

PMID- 25576663
TI  - Synaptic clustering within dendrites: an emerging theory of memory formation.
AB  - It is generally accepted that complex memories are stored in distributed
      representations throughout the brain, however the mechanisms underlying these
      representations are not understood. Here, we review recent findings regarding the
      subcellular mechanisms implicated in memory formation, which provide evidence for
      a dendrite-centered theory of memory. Plasticity-related phenomena which affect
      synaptic properties, such as synaptic tagging and capture, synaptic clustering,
      branch strength potentiation and spinogenesis provide the foundation for a model
      of memory storage that relies heavily on processes operating at the dendrite
      level. The emerging picture suggests that clusters of functionally related
      synapses may serve as key computational and memory storage units in the brain. We
      discuss both experimental evidence and theoretical models that support this
      hypothesis and explore its advantages for neuronal function. 

PMID- 25576665
TI  - Determinants of immunodominance for CD4 T cells.
AB  - The term immunodominance was originally defined as a restricted T cell response
      to a short peptide sequence derived from a given protein. The question of what
      determines immunodominance has been a longstanding battle for the past two
      decades. Hundreds of papers have been written on different aspects of epitope
      selection during antigen processing documenting the complexity of the process.
      Antigen processing machinery involves several accessory molecules and chaperons
      coevolved with proteins of Major Histocompatibility Complex (MHC) molecules that
      each plays its part in epitope selection. These molecules are targeted to
      specialized vesicular compartments that also accommodate antigen processing
      enzymes called cathepsins. Within the antigen processing compartments, highly
      regulated pH gradient and reducing conditions and enzymes necessary for
      denaturation of the antigens are available and function to optimize processing of
      antigen and selection of the fittest for transport to the cell membrane and
      presentation to T cells. Despite the complexity, a cell free reductionist antigen
      processing system was recently reported that included only few purified proteins,
      but was shown to process and select physiologically relevant epitopes from full
      length protein antigens. Due to its minimalist nature the system has been quite
      helpful in dissecting the factors that contribute to epitope selection during
      antigen processing. In this review, we would summarize and highlight models that
      may explain how the dominant epitope may be selected for presentation to CD4(+)
      helper T cells.

PMID- 25576666
TI  - Excessive retinol intake exacerbates choroidal neovascularization through
      upregulated vascular endothelial growth factor in retinal pigment epithelium in
      mice.
AB  - As a part of the visual cycle, all-trans-retinol (all-trans-ROL), the major form
      of vitamin A in circulating blood, is transported to the retinal pigment
      epithelium (RPE). All-trans-ROL is essential for normal retina function. However,
      recent researches have shown that excessive retinol intake can cause increase of
      all-trans-retinal. This can lead to the accumulation of lipofuscin, which is
      important in the pathogenesis of retina degeneration disease, such as dry type
      age-related macular degeneration (AMD). Since there are few reports regarding the
      involvement of all-trans-ROL in exudative AMD, we investigated the effects of all
      trans-ROL in vitro and in vivo. We evaluated vascular endothelial growth factor
      (VEGF) expression in ARPE-19 cells and THP-1 cells after all-trans-ROL treatment
      using ELISA and real-time RT-PCR. In-vitro tube formation assay was performed
      with HUVEC cells using the conditioned medium (CM) obtained from ARPE-19 cells
      treated with all-trans-ROL. Transcriptional activity of retinoic acid receptor
      (RAR) was evaluated using luciferase assay. In mice, VEGF expressions were
      investigated in the retina and RPE/choroid after three weeks of excessive oral
      retinol intake. Laser-induced choroidal neovascularization (CNV) models were
      evaluated after they were fed with various doses of retinol. VEGF mRNA expression
      and VEGF production were significantly increased in all-trans-ROL treated ARPE-19
      cells, which were inhibited by an RAR antagonist LE540. In contrast, there were
      no significant changes in VEGF production in THP-1 cells. Transcriptional
      activity of RAR was upregulated by all-trans-ROL treatment in ARPE-19 cells. The
      CM, obtained from ARPE-19 cells treated with all-trans-ROL, induced more
      capillary-like tube formation than cells treated with control vehicles. In vivo,
      the high retinol diet group has increased VEGF expression in the RPE/choroid and
      larger lesion size was induced. Our results suggest that all-trans-ROL is a pro
      angiogenic factor. Excessive retinoid intake may be a potential risk factor for
      exudative AMD.

PMID- 25576668
TI  - Negative regulation of TGFbeta-induced lens epithelial to mesenchymal transition
      (EMT) by RTK antagonists.
AB  - An eclectic range of ocular growth factors with differing actions are present
      within the aqueous and vitreous humors that bathe the lens. Growth factors that
      exert their actions via receptor tyrosine kinases (RTKs), such as FGF, play a
      normal regulatory role in lens; whereas other factors, such as TGFbeta, can lead
      to an epithelial to mesenchymal transition (EMT) that underlies several forms of
      cataract. The respective downstream intracellular signaling pathways of these
      factors are in turn tightly regulated. One level of negative regulation is
      thought to be through RTK-antagonists, namely, Sprouty (Spry), Sef and Spred that
      are all expressed in the lens. In this study, we tested these different negative
      regulators and compared their ability to block TGFbeta-induced EMT in rat lens
      epithelial cells. Spred expression within the rodent eye was confirmed using RT
      PCR, western blotting and immunofluorescence. Rat lens epithelial explants were
      used to examine the morphological changes associated with TGFbeta-induced EMT
      over 3 days of culture, as well as alpha-smooth muscle actin (alpha-sma)
      immunolabeling. Cells in lens epithelial explants were transfected with either a
      reporter (EGFP) vector (pLXSG), or with plasmids also coding for different RTK
      antagonists (i.e. pLSXG-Spry1, pLSXG-Spry2, pLXSG-Sef, pLSXG-Spred1, pLSXG
      Spred2, pLSXG-Spred3), before treating with TGFbeta for up to 3 days. The
      percentages of transfected cells that underwent TGFbeta-induced morphological
      changes consistent with an EMT were determined using cell counts and validated
      with a paired two-tailed t-test. Explants transfected with pLXSG demonstrated a
      distinct transition in cell morphology after TGFbeta treatment, with ~60% of the
      cells undergoing fibrotic-like cell elongation. This percentage was significantly
      reduced in cells overexpressing the different antagonists, indicative of a block
      in lens EMT. Of the antagonists tested under these in vitro conditions, Spred1
      was the most potent demonstrating the greatest block in TGFbeta-induced fibrotic
      cell elongation/EMT. Through the overexpression of RTK-antagonists in lens
      epithelial cells we have established a novel role for Spry, Spred and Sef as
      negative regulators of TGFbeta-induced EMT. Further investigations may help us
      develop a better understanding of the molecular mechanisms involved in
      maintaining the integrity of the normal lens epithelium, with these antagonists
      serving as putative therapeutic agents for prevention of EMT, and hence
      cataractogenesis. 

PMID- 25576667
TI  - Blue light-induced inflammatory marker expression in the retinal pigment
      epithelium-choroid of mice and the protective effect of a yellow intraocular lens
      material in vivo.
AB  - Oxidative stress in the retinal pigment epithelium (RPE) is a well-accepted
      pathogenic change in vision-threatening diseases such as age-related macular
      degeneration. One source of oxidative stress is excessive light exposure, which
      causes excessive activation of the visual cycle. Because short wavelength light
      (blue light) has more energy, it is reported to be more harmful to photoreceptor
      cells than the other wavelengths of light. However, the biological effect of blue
      light in the RPE of living animals and the protective effect of a yellow
      intraocular lens (IOL) material that blocks blue light is still obscure.
      Therefore, we compared the pathogenic effect in the RPE-choroid complexes of mice
      exposed to light in a box made of a clear or a yellow IOL material. We measured
      the level of reactive oxygen species (ROS) using 2', 7'
      dichlorodihydrofluorescein diacetate, the mRNA levels of inflammatory cytokines
      and a macrophage marker by real-time polymerase chain reaction, and the protein
      level of monocyte chemotactic protein-1 (MCP-1) by ELISA. The ROS level after
      light exposure was suppressed in the RPE-choroids of light-exposed mice in the
      yellow IOL material box. In parallel, all the inflammatory cytokines that we
      measured and a macrophage marker were also suppressed in the RPE-choroids of
      light-exposed mice in the yellow IOL material box. Therefore, a yellow IOL
      material suppressed, and thus blue light exacerbated, the increase in the ROS
      level and inflammatory cytokine expression as well as macrophage recruitment in
      the RPE-choroid in vivo after light exposure. 

PMID- 25576669
TI  - A variant of CLEC16A gene confers protection for Vogt-Koyanagi-Harada syndrome
      but not for Behcet's disease in a Chinese Han population.
AB  - Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) are two common form
      of uveitis in China. The aim of this study was to investigate the association of
      C-type lectin domain family 16, member A (CLEC16A) gene polymorphisms with Vogt
      Koyanagi-Harada syndrome and Behcet's disease in a Chinese Han population. A two
      stage association study was carried out in 988 VKH syndrome patients,400 BD
      patients and 976 healthy controls. Eight single nucleotide polymorphisms of
      CLEC16A gene were determined with the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method. The data were analyzed by chi(2)
      test or Fisher's exact test and corrected for multiple comparisons by the
      Bonferroni method. The first stage study showed that the frequency of the A
      allele of rs6498169 was significantly decreased in VKH syndrome patients (Pc =
      1.1 * 10(-2), OR = 0.7, 95%CI = 0.6-0.9). No significant association was observed
      in the other 7 SNPs between VKH syndrome patients and controls. No association
      was found with BD for the 8 SNPs tested. We further confirmed the association of
      single nucleotide polymorphism rs6498169 with VKH syndrome in another cohort.
      Consistent with the first stage study, the combined study showed significantly
      lower frequencies of the AA genotype and the A allele of rs6498169 in VKH
      syndrome patients (Pc = 3.5 * 10(-4), OR = 0.6, 95%CI = 0.5-0.7; Pc = 8.2 * 10(
      4), OR = 0.8, 95%CI = 0.7-0.9, respectively). In conclusion, the study suggested
      that a CLEC16A polymorphism may be protective against VKH syndrome in a Chinese
      Han population. 

PMID- 25576670
TI  - The diuresis clinic: a new paradigm for the treatment of mild decompensated heart
      failure.
AB  - BACKGROUND: Heart failure results in approximately 1 million hospital admissions
      annually in the United States and is the leading cause of 30-day readmissions.
      METHODS: This study explores the impact of a diuresis clinic on heart failure
      outcomes and cost. Data were collected prospectively on all consecutive patients
      who received intravenous diuretics and multidisciplinary care in the clinic from
      its establishment from October 2011 to December 2012, as well as a comparison
      cohort of patients with heart failure who were admitted to the hospital for <48
      hours. The percentage of hospitalized days was calculated for both cohorts 180
      days before and 180 days after each patient's index visit. RESULTS: In the
      diuresis clinic group, 106 patients (mean age, 68.2 +/- 13 years; 48% were women)
      were treated over 328 visits (1-22 visits per person), with a mean intravenous
      furosemide dose of 100 mg, average urine output of 1460 +/- 730 mL, and weight
      loss of 2.3 +/- 1.8 kg. Days hospitalized decreased from 38.3 to 31.2 per 1000
      patient-days after the index diuresis clinic visit (P < .01). In the comparison
      group, 143 patients (mean age, 69 +/- 16 years; 54% were women) were admitted for
      <48 hours. Days hospitalized increased from 14.4 to 21.0 per 1000 patient-days
      after index admission (P < .01). On multivariate analysis, the diuresis clinic
      was associated with 3 fewer days in the hospital per 180 days per patient, with
      an estimated annual savings of $12,113 per patient. CONCLUSIONS: Compared with a
      brief hospital stay, treatment of mild decompensated heart failure in a diuresis
      clinic resulted in a substantial and cost-effective decline in the rate of
      subsequent hospitalization.

PMID- 25576671
TI  - Treatment with recombinant lubricin attenuates osteoarthritis by positive
      feedback loop between articular cartilage and subchondral bone in ovariectomized
      rats.
AB  - Osteoarthritis (OA) is a most commonly multifactorial degenerative joint disease
      along with the aging population, particularly in postmenopausal women. During the
      onset of OA, articular cartilage and subchondral bone act in concert as a
      functional unit. This present study is to investigate the effects of early or
      late treatment with recombinant lubricin on the onset of osteoarthritis (OA) in
      ovariectomized (OVX) rats. We found that both early and late recombinant lubricin
      treatments attenuated the onset of OA by positive feedback loop between articular
      cartilage and subchondral bone, although late treatment contributed to a lesser
      effect compared with early treatment. Specifically, treatment with recombinant
      lubricin protected articular cartilage from degeneration, demonstrated by lower
      proteoglycan loss, lower OARSI scores, less calcification cartilage zone and
      reduced immunostaining for collagen X (Col X) and matrix metalloproteinase (MMP
      13) but increased the expression of lubricin, in comparison with vehicle-treated
      OVX rat group. Further, chondroprotective effects of lubricin normalized bone
      remodeling in subchondral bone underneath. It's suggested that treatment with
      recombinant lubricin inhibited the elevation of TRAP and Osterix positive cells
      in OVX rats and led to the normalization of subchondral bone microarchitectures
      with the suppression of subsidence of bone volume ratio (BV/TV) and trabecular
      thickness (Tb.Th) and the increase of trabecular separation (Tb.Sp) in vehicle
      treated OVX rats. What's more, the normalization of subchondral bone in turn
      attenuated the articular cartilage erosion by inhibiting vascular invasion from
      subchondral bone to calcified cartilage zone, exemplified by inhibiting the
      elevation of CD31 positive cells in calcified cartilage and angiography in
      subchondral bone. Together, these results shed light that both early and late
      recombinant lubricin treatments attenuate the onset of OA by balancing the
      interplay between articular cartilage and subchondral bone in OVX rats, while
      also providing a further rationale for its therapeutic targeting to
      postmenopausal OA and suggesting that treatment timing is a pivotal factor for
      better effect acquisition. 

PMID- 25576673
TI  - Impact of demographic, environmental, and lifestyle factors on vitamin D
      sufficiency in 9084 Japanese adults.
AB  - BACKGROUND: Little is known about correlates of vitamin D status in Asian
      populations. In this study, we established the prevalence of vitamin D
      sufficiency in the Murakami region (latitude N38 degrees 13') in Niigata, Japan,
      and examined demographic, environmental, and lifestyle factors that might be
      associated with vitamin D sufficiency, with the aim of clarifying the relative
      contributions of previously described determinants of vitamin D status as well as
      identifying new determinants in this Japanese population. METHODS: This study
      involved a cross-sectional analysis of baseline data obtained from a cohort study
      conducted in 2011-2013. Participants were 9084 individuals aged between 40 and 74
      years who provided blood samples for the determination of plasma 25
      hydroxyvitamin D [25(OH)D] concentrations. Lifestyle information was obtained
      from 8498 participants, with some missing values regarding different lifestyle
      factors. Multiple logistic regression analysis was used to obtain odds ratios for
      vitamin D sufficiency, which was defined as a plasma 25(OH)D concentration >= 75
      nmol/L. RESULTS: The prevalence of vitamin D sufficiency (i.e., plasma 25(OH)D
      concentration >= 75 nmol/L) was 9.1%, and significant associations were observed
      with male gender (P<0.0001; OR=2.37, 95% CI: 1.84-3.05), older age (P for trend
      <0.0001), lower BMI (P for trend <0.0001), higher METs score (P for
      trend=0.0138), higher vitamin D intake (P for trend=0.0467), summer season (P for
      trend <0.0001), longer duration outdoors (P for trend=0.0026), no sunscreen use
      (P=0.0135; OR=1.40, 95% CI: 1.07-1.82), higher salmon consumption (P for trend
      <0.0001), higher alcohol consumption (P for trend <0.0001), and lower coffee
      consumption (P for trend=0.0025). Unlike other populations previously reported,
      vitamin D sufficiency was associated with older age. CONCLUSIONS: The prevalence
      of vitamin D sufficiency (i.e., 25[OH]D >= 75 nmol/L) was low (9.1%) in this
      Japanese population. A number of demographic, environmental, and lifestyle
      factors are associated with vitamin D sufficiency, and thus lifestyle
      modification may present an opportunity to achieve vitamin D sufficiency.

PMID- 25576672
TI  - Diabetes and fracture risk in older U.S. adults.
AB  - OBJECTIVE: We examined the diabetes-fracture relationship by race/ethnicity,
      including the link between pre-diabetes and fracture. RESEARCH DESIGN AND
      METHODS: We used Medicare- and mortality-linked data for respondents aged 65years
      and older from the third National Health and Nutrition Examination Survey (NHANES
      III) and NHANES 1999-2004 for three race/ethnic groups: non-Hispanic whites
      (NHW), non-Hispanic blacks (NHB), and Mexican Americans (MA). Diabetes was
      defined as diagnosed diabetes (self-reported) and diabetes status: diagnosed and
      undiagnosed diabetes (positive diagnosis or hemoglobin A1c (A1C)>=6.5%); pre
      diabetes (no diagnosis and A1C between 5.7% and 6.4%); and no diabetes (no
      diagnosis and A1C<5.7%). Non-skull fractures (n=750) were defined using published
      algorithms. Hazards ratios (HRs) were calculated using Cox proportional hazards
      models. RESULTS: The diabetes-fracture relationship differed significantly by
      race/ethnicity (pinteraction<0.05). Compared to those without diagnosed diabetes,
      the HRs for those with diagnosed diabetes were 2.37 (95% CI 1.49-3.75), 1.87 (95%
      CI 1.02-3.40), and 1.22 (95% CI 0.93-1.61) for MA, NHB, and NHW, respectively,
      after adjusting for significant confounders. HRs for diagnosed and undiagnosed
      diabetes were similar to those for diagnosed diabetes alone. Pre-diabetes was not
      significantly related to fracture risk, however. Compared to those without
      diabetes, adjusted HRs for those with pre-diabetes were 1.42 (95% CI 0.72-2.81),
      and 1.20 (95% CI 0.96-1.51) for MA and NHW, respectively. There were insufficient
      fracture cases to examine detailed diabetes status in NHB. CONCLUSIONS: The
      diabetes-fracture relationship was stronger in MA and NHB. Pre-diabetes was not
      significantly associated with higher fracture risk, however.

PMID- 25576674
TI  - Deletion of Nrf2 reduces skeletal mechanical properties and decreases load-driven
      bone formation.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor
      expressed in many cell types, including osteoblasts, osteocytes, and osteoclasts.
      Nrf2 has been considered a master regulator of cytoprotective genes against
      oxidative and chemical insults. The lack of Nrf2 can induce pathologies in
      multiple organs. The aim of this study was to investigate the role of Nrf2 in
      load-driven bone metabolism using Nrf2 knockout (KO) mice. Compared to age
      matched littermate wild-type controls, Nrf2 KO mice have significantly lowered
      femoral bone mineral density (-7%, p<0.05), bone formation rate (-40%, p<0.05),
      as well as ultimate force (-11%, p<0.01). The ulna loading experiment showed that
      Nrf2 KO mice were less responsive than littermate controls, as indicated by
      reduction in relative mineralizing surface (rMS/BS, -69%, p<0.01) and relative
      bone formation rate (rBFR/BS, -84%, p<0.01). Furthermore, deletion of Nrf2
      suppressed the load-driven gene expression of antioxidant enzymes and Wnt5a in
      cultured primary osteoblasts. Taken together, the results suggest that the loss
      of-function mutation of Nrf2 in bone impairs bone metabolism and diminishes load
      driven bone formation. 

PMID- 25576675
TI  - Detection of methamphetamine and its main metabolite in fingermarks by liquid
      chromatography-mass spectrometry.
AB  - A sensitive and efficient method applying liquid chromatography-mass spectrometry
      for the analysis of methamphetamine and its main metabolite in fingermark
      deposits was described. Using this method, good linear relationship of
      methamphetamine was obtained in the range of 0.005MUg to 0.5MUg per cotton swab,
      the limit of detection was 1.5ng per cotton swab, the limit of quantitation was
      5.0ng per cotton swab and the average values of recovery ratios were above 70.1%.
      Moreover, the influence factors for the detection of methamphetamine in
      fingermarks, such as kinds of substrates, development methods and extraction
      methods, were all discussed in details. The results showed that good recovery
      ratios could be obtained on painted wood and smooth substrates surfaces.
      Development methods in commercial powder could not influence the quality of
      examination of exogenous drug in latent fingermark. Furthermore, the results
      indicated that the method mentioned here could be applied in the analysis of
      forensic trace evidences and samples obtained in clinically addicted cases. 

PMID- 25576677
TI  - Modelling of facial growth in Czech children based on longitudinal data: Age
      progression from 12 to 15 years using 3D surface models.
AB  - Dealing with the increasing number of long-term missing children and juveniles
      requires more precise and objective age progression techniques for the prediction
      of their current appearance. Our contribution includes detailed and real facial
      growth information used for modelling age progression during adolescence. This
      study was based on an evaluation of the overall 180 three-dimensional (3D) facial
      scans of Czech children (23 boys, 22 girls), which were longitudinally studied
      from 12 to 15 years of age and thus revealed the real growth-related changes. The
      boys underwent more marked changes compared with the girls, especially in the
      regions of the eyebrow ridges, nose and chin. Using modern geometric morphometric
      methods, together with their applications, we modelled the ageing and allometric
      trajectories for both sexes and simulated the age-progressed effects on facial
      scans. The facial parts that are important for facial recognition (eyes, nose,
      mouth and chin) all deviated less than 0.75mm, whereas the areas with the largest
      deviations were situated on the marginal parts of the face. The mean error
      between the predicted and real facial morphology obtained by modelling the
      children from 12 to 15 years of age was 1.92mm in girls and 1.86mm in boys. This
      study is beneficial for forensic artists as it reduces the subjectivity of age
      progression methods. 

PMID- 25576676
TI  - Forensic intelligence for medicine anti-counterfeiting.
AB  - Medicine counterfeiting is a crime that has increased in recent years and now
      involves the whole world. Health and economic repercussions have led
      pharmaceutical industries and agencies to develop many measures to protect
      genuine medicines and differentiate them from counterfeits. Detecting counterfeit
      is chemically relatively simple for the specialists, but much more information
      can be gained from the analyses in a forensic intelligence perspective.
      Analytical data can feed criminal investigation and law enforcement by detecting
      and understanding the criminal phenomenon. Profiling seizures using chemical and
      packaging data constitutes a strong way to detect organised production and
      industrialised forms of criminality, and is the focus of this paper. Thirty-three
      seizures of a commonly counterfeited type of capsule have been studied. The
      results of the packaging and chemical analyses were gathered within an organised
      database. Strong linkage was found between the seizures at the different
      production steps, indicating the presence of a main counterfeit network
      dominating the market. The interpretation of the links with circumstantial data
      provided information about the production and the distribution of counterfeits
      coming from this network. This forensic intelligence perspective has the
      potential to be generalised to other types of products. This may be the only
      reliable approach to help the understanding of the organised crime phenomenon
      behind counterfeiting and to enable efficient strategic and operational decision
      making in an attempt to dismantle counterfeit network. 

PMID- 25576678
TI  - How can age and lifestyle variables affect DNA damage, repair capacity and
      endogenous biomarkers of oxidative stress?
AB  - Age-related DNA damage has been regarded as one of the possible explanations of
      aging, and these age-related changes have been associated with lifestyle
      variables. Considering this, the purpose of this study was to investigate how age
      and lifestyle may affect DNA damage, DNA repair capacity and endogenous
      biomarkers of oxidative stress. Sixty-one healthy men (40 to 89 yrs) were
      enrolled in this study. The results showed that DNA strand breaks (DNA SBs) and
      DNA repair capacity were greater in the older group (>=65 yrs) compared to the
      younger group (<65 yrs) (p<0.05). FPG-sensitive sites, total antioxidant capacity
      and lipid peroxidation (MDA) were not statistically different between groups. The
      correlation test showed that DNA damage variables were not correlated with any
      lifestyle variable excepting DNA SBs which was correlated with aerobic capacity
      (6MWT). DNA SBs and DNA repair were positively correlated with age. The multiple
      regression analysis revealed that the aerobic capacity (6MWT) and MDA were the
      predictors for the variation of DNA SBs (41.9%). In conclusion these results
      suggest that DNA SB damage increases with age but not FPG-sensitive sites.
      Moreover, base excision repair capacity increases with age without the increase
      of oxidative damage to DNA. The most predictable variables of DNA SBs were the
      aerobic capacity and MDA.

PMID- 25576679
TI  - Outcome in acute heart failure: prognostic value of acute kidney injury and
      worsening renal function.
AB  - BACKGROUND: The prognostic value of worsening renal function (WRF) in acute heart
      failure is debated. Moreover, it is not clear if the use of angiotensin
      converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in
      this context is detrimental. METHOD AND RESULTS: In a retrospective cohort study
      of 646 patients hospitalized for acute heart failure, the risk of death or
      readmission associated with acute kidney injury (AKI) present at admission, WRF
      during the 1st 7 days, and up-titration of ACEI/ARB were analyzed in a Cox
      proportional hazards model. AKI, WRF, hemoglobin concentration, ACEI/ARB up
      titration, and use of loop diuretics before admission were significantly
      associated with the primary outcome in univariate analysis. In a multivariate
      model, the association remained significant for AKI (hazard ratio [HR] 1.29, 95%
      confidence interval [CI] 1.13-1.47; P = .0002), WRF (HR 1.24, 95% CI 1.06-1.45; P
      = .0059), and ACEI/ARB up-titration (HR 0.79, 95% CI 0.64-0.97; P = .026). There
      was no excess mortality in patients with ACEI/ARB up-titration despite WRF.
      CONCLUSIONS: Both AKI and WRF are strongly associated with poor outcome in
      patients hospitalized for acute heart failure. ACEI/ARB up-titration seems to be
      protective.

PMID- 25576680
TI  - Dietary sodium adherence is poor in chronic heart failure patients.
AB  - BACKGROUND: We sought to determine the rates and predictors of dietary sodium
      restriction and to evaluate the reliability of 24-hour urine collection as a tool
      to estimate dietary sodium intake in heart failure (HF) patients. METHODS AND
      RESULTS: We evaluated the 24-hour urinary sodium excretion of 305 outpatients
      with HF and reduced ejection fraction who were educated on following a <2 g
      sodium diet. The mean sodium excretion according to a single sample from each
      participant was 3.15 +/- 1.58 g, and 23% were adherent to the <2 g
      recommendation. One hundred sixty-eight participants provided 2 samples with
      urinary creatinine excretion within normative range. Averaging both resulted in a
      mean sodium excretion of 3.21 +/- 1.20 g and lower adherence rates to the <2-gram
      diet: 14% versus 23% (P = .019). Multivariate logistic regression showed only
      male sex and higher body mass index (BMI) to be associated with nonadherence
      (male: odds ratio [OR] 2.20, 95% confidence interval [CI] 1.25-3.88; 1 unit BMI:
      OR 1.05, 95% CI 1.01-1.10). Bland-Altman plots of urinary sodium and creatinine
      showed poor reproducibility between samples. CONCLUSIONS: In this chronic HF
      population, sodium consumption probably exceeds recommended amounts, particularly
      in men and those with higher BMI. Urine analyses were not highly reproducible,
      suggesting variation in both diet and urine collection.

PMID- 25576681
TI  - Modulation of ventilatory reflex control by cardiac resynchronization therapy.
AB  - BACKGROUND: Heart failure (HF) is characterized by heightened sensitivities of
      the CO2 chemoreflex and the ergoreflex which promote increased ventilatory drive
      manifested as increased minute ventilation per volume of expired CO2 (VE/VCO2).
      The aims of this study were to evaluate the effects of cardiac resynchronization
      therapy (CRT) on carbon dioxide (CO2) chemosensitivity and the arterial CO2
      setpoint. METHODS AND RESULTS: Consecutive HF patients (n = 35) who underwent
      clinically indicated CRT were investigated by means of cardiopulmonary exercise
      testing and CO2 chemosensitivity evaluation with the use of a rebreathe method
      before and 4-6 months after CRT. Pre- and post-CRT measures were compared with
      the use of either paired t test or Wilcoxon test. Decreased peak VE/VCO2 (44 +/-
      10 vs 40 +/- 8; P < .01), CO2 chemosensitivity (2.2 +/- 1.1 vs 1.7 +/- 0.8 L min(
      1) mm Hg(-1); P = .04), and increased peak end-tidal CO2 (29 +/- 5 vs 31 +/- 5 mm
      Hg; P < .01) were also observed after CRT. Multivariate analysis adjusted for age
      and sex showed the decrease of peak VE/VCO2 from before to after CRT to be most
      strongly associated with the increase of peak end-tidal CO2 (beta = -0.84; F =
      21.5; P < .0001). CONCLUSIONS: Decrease of VE/VCO2 after CRT is associated with
      decreased CO2 chemosensitivity and increase of the arterial CO2 setpoint, which
      is consistent with decreased activation of both the CO2 chemoreflex and the
      ergoreflex.

PMID- 25576682
TI  - Differential prognostic impact of resting heart rate in older compared with
      younger patients with chronic heart failure--insights from TIME-CHF.
AB  - BACKGROUND: There is little information regarding the prognostic role of resting
      heart rate (HR) in older compared with younger patients with chronic heart
      failure (HF). METHODS AND RESULTS: In patients enrolled in the Trial of
      Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure
      (TIME-CHF) with sinus rhythm, effects of baseline HR (>=70 vs <70 beats/min
      [bpm]) on 18-month outcomes were compared between older (>=75 years; n = 186) and
      younger (<75 years; n = 141) patients. Older patients with lower (61 +/- 6 bpm)
      and higher (83 +/- 9 bpm) HR had similar left ventricular ejection fraction
      (LVEF), New York Heart Association (NYHA) functional class, N-terminal pro-B-type
      natriuretic peptide (NT-proBNP), and survival and HF hospitalization-free
      survival. In contrast, younger patients with higher HR (81 +/- 7 bpm) had higher
      NT-proBNP and NYHA functional class, lower LVEF, and a higher risk of death
      (hazard ratio 4.01 [95% confidence interval (CI) 1.17 -13.69]; P = .02) and death
      or HF hospitalization (hazard ratio 2.35 [95% CI 1.01-5.50]; P = .04) than those
      with lower HR (62 +/- 5 bpm), with the association between higher HR and survival
      remaining significant after adjustment for NYHA functional class, LVEF, and NT
      proBNP. CONCLUSIONS: In contrast to HF patients aged <75 years, we found no
      association between HR and worse outcomes in HF patients aged >=75 years.

PMID- 25576683
TI  - Structural bisphenol analogues differentially target steroidogenesis in murine MA
      10 Leydig cells as well as the glucocorticoid receptor.
AB  - Although much information on the endocrine activity of bisphenol A (BPA) is
      available, a proper human hazard assessment of analogues that are believed to
      have a less harmful toxicity profile is lacking. Here the possible effects of
      BPA, bisphenol F (BPF), bisphenol S (BPS), as well as the brominated structural
      analogue and widely used flame retardant tetrabromobisphenol A (TBBPA) on human
      glucocorticoid and androgen receptor (GR and AR) activation were assessed. BPA,
      BPF, and TBBPA showed clear GR and AR antagonism with IC50 values of 67 MUM, 60
      MUM, and 22 nM for GR, and 39 MUM, 20 MUM, and 982 nM for AR, respectively,
      whereas BPS did not affect receptor activity. In addition, murine MA-10 Leydig
      cells exposed to the bisphenol analogues were assessed for changes in secreted
      steroid hormone levels. Testicular steroidogenesis was altered by all bisphenol
      analogues tested. TBBPA effects were more directed towards the male end products
      and induced testosterone synthesis, while BPF and BPS predominantly increased the
      levels of progestagens that are formed in the beginning of the steroidogenic
      pathway. The MA-10 Leydig cell assay shows added value over the widely used H295R
      steroidogenesis assay because of its fetal-like characteristics and specificity
      for the physiologically more relevant testicular Delta4 steroidogenic pathway.
      Therefore, adding an in vitro assay covering fetal testicular steroidogenesis,
      such as the MA-10 cell line, to the panel of tests used to screen potential
      endocrine disruptors, is highly recommendable.

PMID- 25576684
TI  - Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin.
AB  - Understanding the mechanism of action of the yessotoxin (YTX) is crucial since
      this drug has potential pharmacological effects in allergic processes, tumor
      proliferation and neurodegenerative diseases. It has been described that YTX
      activates apoptosis after 24h of treatment, while after 48 h of incubation with
      the toxin a decrease in cell viability corresponding to cellular differentiation
      or non-apoptotic cell death was observed. In this paper, these processes were
      extensively studied by using the erythroleukemia K-562 cell line. On one hand,
      events of K-562 cell differentiation into erythrocytes after YTX treatment were
      studied using hemin as positive control of cell differentiation. Cell
      differentiation was studied through the cyclic nucleotide response element
      binding (phospho-CREB) and the transferrin receptor (TfR) expression. On the
      other hand, using rapamycin as positive control, autophagic hallmarks, as non
      apoptotic cell death, were studied after toxin exposure. In this case, the
      mechanistic target of rapamycin (mTOR) and light chain 3B (LC3B) levels were
      measured to check autophagy activation. The results showed that cell
      differentiation was not occurring after 48 h of toxin incubation while at this
      time the autophagy was triggered. Furthermore after 24h of toxin treatment none
      of these processes were activated. In addition, the role of the type 4A
      phosphodiesterase (PDE4A), the intracellular target of YTX, was checked. PDE4A
      silencing experiments showed different regulation steps of PDE4A in the
      autophagic processes triggered either by traditional compounds or YTX. In
      summary, after 48 h YTX treatment PDE4A-dependent autophagy, as non-apoptotic
      programmed cell death, is activated.

PMID- 25576685
TI  - Telmisartan attenuates the inflamed mesenteric adipose tissue in spontaneous
      colitis by mechanisms involving regulation of neurotensin/microRNA-155 pathway.
AB  - Mesenteric adipose tissue hypertrophy is unique to Crohn's disease while the
      molecular basis of the crosstalk between MAT and the intestinal inflammation is
      largely unknown. Telmisartan is an angiotensin II type 1 receptor blocker and a
      peroxisome proliferator-activated receptor-receptor-gamma agonist which has
      beneficial effects on fat distribution and pro-inflammatory adipokine expression.
      We evaluated the effect of telmisartan upon mesenteric adipose tissue alterations
      and inflammatory features in IL-10(-)/(-) mice. We found that treatment with
      telmisartan significantly ameliorated the severity of colitis in IL-10(-)/(-)
      mice. Additionally, administration of telmisartan was associated with restoration
      of mesenteric adipose tissue adipocyte morphology and the expression of
      adipokines. Furthermore, telmisartan treatment suppressed the
      neurotensin/microRNA-155 pathway in mesenteric adipose tissue from spontaneous
      colitis which was confirmed by an in vitro study using cultured mesenteric
      adipose tissue from Crohn's disease patients. Administration of telmisartan
      showed promising results in spontaneous colitis which was associated with the
      attenuated mesenteric adipose tissue alteration which at least in part, was
      associated with its activity in the regulation of the neurotensin/microRNA-155
      pathway. These results support the hypothesis that regulating the abnormal immune
      response in adipose tissue is an important target for the treatment of Crohn's
      disease. 

PMID- 25576686
TI  - Aldehyde dehydrogenase-independent bioactivation of nitroglycerin in porcine and
      bovine blood vessels.
AB  - The vascular bioactivation of the antianginal drug nitroglycerin (GTN), yielding
      1,2-glycerol dinitrate and nitric oxide or a related activator of soluble
      guanylate cyclase, is catalyzed by aldehyde dehydrogenase-2 (ALDH2) in rodent and
      human blood vessels. The essential role of ALDH2 has been confirmed in many
      studies and is considered as general principle of GTN-induced vasodilation in
      mammals. However, this view is challenged by an early report showing that
      diphenyleneiodonium, which we recently characterized as potent ALDH2 inhibitor,
      has no effect on GTN-induced relaxation of bovine coronary arteries (De La Lande
      et al., 1996). We investigated this issue and found that inhibition of ALDH2
      attenuates GTN-induced coronary vasodilation in isolated perfused rat hearts but
      has no effect on relaxation to GTN of bovine and porcine coronary arteries. This
      observation is explained by low levels of ALDH2 protein expression in bovine
      coronary arteries and several types of porcine blood vessels. ALDH2 mRNA
      expression and the rates of GTN denitration were similarly low, excluding a
      significant contribution of ALDH2 to the bioactivation of GTN in these vessels.
      Attempts to identify the responsible pathway with enzyme inhibitors did not
      provide conclusive evidence for the involvement of ALDH3A1, cytochrome P450, or
      GSH-S-transferase. Thus, the present manuscript describes a hitherto unrecognized
      pathway of GTN bioactivation in bovine and porcine blood vessels. If present in
      the human vasculature, this pathway might contribute to the therapeutic effects
      of organic nitrates that are not metabolized by ALDH2. 

PMID- 25576688
TI  - Reply: To PMID 24161349.

PMID- 25576687
TI  - Metoclopramide Nasal Spray Reduces Symptoms of Gastroparesis in Women, but not
      Men, With Diabetes: Results of a Phase 2B Randomized Study.
AB  - BACKGROUND & AIMS: Metoclopramide nasal spray, unlike oral tablets, is absorbed
      even when patients have delayed gastric emptying or nausea and vomiting. We
      performed a randomized phase 2b study to evaluate the efficacy and safety of 10
      mg and 14-mg metoclopramide nasal spray vs placebo in patients with diabetes and
      gastroparesis. METHODS: We performed a multicenter, double-blind study of 285
      subjects (71% female) with type 1 or type 2 diabetes and a previous diagnosis of
      gastroparesis. Subjects were assigned randomly to groups given metoclopramide
      nasal spray (10 or 14 mg) or placebo 30 minutes before meals and bedtime for 28
      days. The primary end point was the change in total symptom score from baseline
      to week 4, based on symptom items (nausea, bloating, early satiety, and upper
      abdominal pain) reported in daily diaries. We performed a prespecified subgroup
      analysis of male vs female subjects. RESULTS: Subjects given metoclopramide nasal
      spray had an overall reduction in symptom scores, although there was no
      statistically significant difference in reduction between the metoclopramide
      groups and the placebo group. Gastroparesis symptom scores were reduced
      significantly in female subjects given either dose of metoclopramide compared
      with placebo (mean reduction from 10-mg dose, 1.2 +/- 1.18; P = .0247; mean
      reduction from 14-mg dose, 1.3 +/- 0.94; P = .0215). In men, symptom scores
      decreased more in the placebo group than the metoclopramide groups. The most
      common treatment-emergent adverse effects were dysgeusia, headache, and fatigue.
      CONCLUSIONS: Metoclopramide nasal spray reduces symptoms of gastroparesis in
      women, but not in men, with diabetes. Patient sex therefore might be considered
      in the selection of treatment for diabetic gastroparesis. ClinicalTrials.gov no:
      NCT00845858.

PMID- 25576689
TI  - Industry payments to gastroenterologists across the United States.

PMID- 25576690
TI  - Localising semantic and syntactic processing in spoken and written language
      comprehension: an Activation Likelihood Estimation meta-analysis.
AB  - We conducted an Activation Likelihood Estimation (ALE) meta-analysis to identify
      brain regions that are recruited by linguistic stimuli requiring relatively
      demanding semantic or syntactic processing. We included 54 functional MRI studies
      that explicitly varied the semantic or syntactic processing load, while holding
      constant demands on earlier stages of processing. We included studies that
      introduced a syntactic/semantic ambiguity or anomaly, used a priming manipulation
      that specifically reduced the load on semantic/syntactic processing, or varied
      the level of syntactic complexity. The results confirmed the critical role of the
      posterior left Inferior Frontal Gyrus (LIFG) in semantic and syntactic
      processing. These results challenge models of sentence comprehension highlighting
      the role of anterior LIFG for semantic processing. In addition, the results
      emphasise the posterior (but not anterior) temporal lobe for both semantic and
      syntactic processing. 

PMID- 25576691
TI  - alpha integrin cytoplasmic tails can rescue the loss of Rho-family GTPase
      signaling in the C. elegans somatic gonad.
AB  - Integrin signaling relies on multiple, distinct pathways to impact a diverse set
      of cell behaviors. The Rho family of GTPases are well-established downstream
      signaling partners of integrins that regulate cell shape, polarity, and
      migration. The nematode C. elegans provides a simple in vivo system for studying
      both integrins and the Rho family. Our previous work showed that the C. elegans
      alpha integrin cytoplasmic tails have tissue-specific functions during
      development. Here, we use chimeric alpha integrins to show that the cytoplasmic
      tails can rescue the loss of the Rho family of GTPases in three cell types in the
      somatic gonad. Knockdown of rho-1 by RNAi causes defects in sheath cell actin
      organization, ovulation, and vulva morphology. Chimeric alpha integrin ina-1 with
      the pat-2 cytoplasmic tail can rescue both actin organization and ovulation after
      rho-1 RNAi, yet cannot restore vulva morphology. Knockdown of cdc-42 by RNAi
      causes defects in sheath cell actin organization, ovulation, vulva morphology,
      and distal tip cell migration. Chimeric alpha integrin pat-2 with the ina-1
      cytoplasmic tail can rescue vulva morphology defects and distal tip cell
      migration after cdc-42 RNAi, yet cannot restore sheath cell actin organization or
      ovulation. Disruption of Rac yields the same phenotype in distal tip cells
      regardless of alpha integrin cytoplasmic tail composition. Taken together, the
      cytoplasmic tails of alpha integrins can bypass signaling from members of the Rho
      family of GTPases during development. 

PMID- 25576692
TI  - Spectroscopic examination of effects of iodide on the chloramination of natural
      organic matter.
AB  - This study examined reactions of NOM with chloramine in the presence of varying
      iodide concentrations using in situ methods of absorbance and fluorescence. The
      data showed that the consumption of iodide during chloramination could be
      quantified by the differential absorbance of NOM at 225 nm. Examination of the
      kinetics of iodide consumption demonstrated the presence of two different
      reaction stages corresponding to the engagement of fast and slow reactive site in
      NOM. Interactions between the fast site and chloramine in the presence of iodide
      did not show specific effects of the incorporation of iodine compared to that of
      chlorine but the engagement of the slow site caused changes of NOM fluorophores
      and chromophores specific to iodine. Comparison of changes of the slope of log
      processed NOM absorbance spectra (S325-350) and decreases of NOM fluorescence
      intensity showed the presence of heavy atom effects whose extent was proportional
      to the incorporation of iodine in the organic substrate. The data also indicated
      that the engagement of the slow site was accompanied by the formation of
      intermediate species whose nature remains to be elucidated.

PMID- 25576693
TI  - From the affinity constant to the half-saturation index: understanding
      conventional modeling concepts in novel wastewater treatment processes.
AB  - The "affinity constant" (KS) concept is applied in wastewater treatment models to
      incorporate the effect of substrate limitation on process performance. As an
      increasing number of wastewater treatment processes rely on low substrate
      concentrations, a proper understanding of these so-called constants is critical
      in order to soundly model and evaluate emerging treatment systems. In this paper,
      an in-depth analysis of the KS concept has been carried out, focusing on the
      different physical and biological phenomena that affect its observed value. By
      structuring the factors influencing half-saturation indices (newly proposed
      nomenclature) into advectional, diffusional and biological, light has been shed
      onto some of the apparent inconsistencies present in the literature.
      Particularly, the importance of non-ideal mixing as a source of variability
      between observed KS values in different systems has been illustrated.
      Additionally, discussion on the differences existent between substrates that
      affect half-saturation indices has been carried out; it has been shown that the
      observed KS for some substrates will reflect transport or biological limitations
      more than others. Finally, potential modeling strategies that could alleviate the
      shortcomings of the KS concept have been provided. These could be of special
      importance when considering the evaluation and design of emerging wastewater
      treatment processes. 

PMID- 25576694
TI  - Pathogen transport and fate modeling in the Upper Salem River Watershed using
      SWAT model.
AB  - Simulation of the fate and transport of pathogen contamination was conducted with
      SWAT for the Upper Salem River Watershed, located in Salem County, New Jersey.
      This watershed is 37 km(2) and land uses are predominantly agricultural. The
      watershed drains to a 32 km stretch of the Salem River upstream of the head of
      tide. This strech is identified on the 303(d) list as impaired for pathogens. The
      overall goal of this research was to use SWAT as a tool to help to better
      understand how two pathogen indicators (Escherichia coli and fecal coliform) are
      transported throughout the watershed, by determining the model parameters that
      control the fate and transport of these two indicator species. This effort was
      the first watershed modeling attempt with SWAT to successfully simulate E. coli
      and fecal coliform simultaneously. Sensitivity analysis has been performed for
      flow as well as fecal coliform and E. coli. Hydrologic calibration at six
      sampling locations indicate that the model provides a "good" prediction of
      watershed outlet flow (E = 0.69) while at certain upstream calibration locations
      predictions are less representative (0.32 < E < 0.70). Monthly calibration and
      validation of the pathogen transport and fate model was conducted for both fecal
      coliform (0.07 < E < 0.47 and -0.94 < E < 0.33) and E. coli (0.03 < E < 0.39 and 
      0.81 < E < 0.31) for the six sampling points. The fit of the model compared
      favorably with many similar pathogen modeling efforts. The research contributes
      new knowledge in E. coli and fecal coliform modeling and will help increase the
      understanding of sensitivity analysis and pathogen modeling with SWAT at the
      watershed scale.

PMID- 25576695
TI  - Reduction of sediment internal P-loading from eutrophic lakes using thermally
      modified calcium-rich attapulgite-based thin-layer cap.
AB  - We conducted a laboratory evaluation of a low-cost P-capping agent-700 degrees C
      heated natural calcium-rich attapulgite (NCAP700)-in terms of its ability to
      reduce internal P-loading in lake sediments. Batch studies indicated that NCAP700
      could effectively reduce sediment mobile P (P mobile) in various types of lake
      sediment, and the dosage equation required to immobilize P mobile was developed
      accordingly. The equation was then applied to a laboratory incubation study on
      intact sediment cores. The results indicated that the NCAP700-based thin-layer
      cap can enhance the redox potential (Eh), pH and dissolved oxygen (DO) in surface
      sediment. However, this enhancing effect was decreased with increasing time. P
      fluxes and the concentration of P in overlying water and pore water from sediment
      could be effectively inhibited under anaerobic conditions. P fractionation
      analysis indicated that 34.5% of P mobile was bound in the upper 2 cm sediment
      layer during a 40-day remediation period, but this only exerted a minor influence
      on the P mobile in the 2-4 cm sediment layer. P immobilization by NCAP700 was
      mainly achieved through transformation of P mobile to stable Ca-P. These results
      indicate that NCAP700 can be used for lake eutrophication control by means of
      thin-layer capping.

PMID- 25576696
TI  - Modeling climate change, urbanization, and fire effects on Pinus palustris
      ecosystems of the southeastern U.S.
AB  - Managing ecosystems for resilience and sustainability requires understanding how
      they will respond to future anthropogenic drivers such as climate change and
      urbanization. In fire-dependent ecosystems, predicting this response requires a
      focus on how these drivers will impact fire regimes. Here, we use scenarios of
      climate change, urbanization and management to simulate the future dynamics of
      the critically endangered and fire-dependent longleaf pine (Pinus palustris)
      ecosystem. We investigated how climate change and urbanization will affect the
      ecosystem, and whether the two conservation goals of a 135% increase in total
      longleaf area and a doubling of fire-maintained open-canopy habitat can be
      achieved in the face of these drivers. Our results show that while climatic
      warming had little effect on the wildfire regime, and thus on longleaf pine
      dynamics, urban growth led to an 8% reduction in annual wildfire area. The
      management scenarios we tested increase the ecosystem's total extent by up to 62%
      and result in expansion of open-canopy longleaf by as much as 216%, meeting one
      of the two conservation goals for the ecosystem. We find that both conservation
      goals for this ecosystem, which is climate-resilient but vulnerable to
      urbanization, are only attainable if a greater focus is placed on restoration of
      non-longleaf areas as opposed to maintaining existing longleaf stands. Our
      approach demonstrates the importance of accounting for multiple relevant
      anthropogenic threats in an ecosystem-specific context in order to facilitate
      more effective management actions. 

PMID- 25576697
TI  - Recovery and biological oxidation of dissolved methane in effluent from UASB
      treatment of municipal sewage using a two-stage closed downflow hanging sponge
      system.
AB  - A two-stage closed downflow hanging sponge (DHS) reactor was used as a post
      treatment to prevent methane being emitted from upflow anaerobic sludge blanket
      (UASB) effluents containing unrecovered dissolved methane. The performance of the
      closed DHS reactor was evaluated using real municipal sewage at ambient
      temperatures (10-28  degrees C) for one year. The first stage of the closed DHS
      reactor was intended to recover dissolved methane from the UASB effluent and
      produce a burnable gas with a methane concentration greater than 30%, and its
      recovery efficiency was 57-88%, although the amount of dissolved methane in the
      UASB effluent fluctuated in the range of 46-68 % of methane production greatly
      depending on the temperature. The residual methane was oxidized and the remaining
      organic carbon was removed in the second closed DHS reactor, and this reactor
      performed very well, removing more than 99% of the dissolved methane during the
      experimental period. The rate at which air was supplied to the DHS reactor was
      found to be one of the most important operating parameters. Microbial community
      analysis revealed that seasonal changes in the methane-oxidizing bacteria were
      key to preventing methane emissions.

PMID- 25576698
TI  - Effects of non-consumptive wildlife-oriented tourism on marine species and
      prospects for their sustainable management.
AB  - Marine non-consumptive wildlife-oriented tourism, whereby tourists observe and/or
      interact closely with animals, without purposely having a detrimental effect on
      them, has been growing globally in recent decades. Human-mediated feeding
      (provisioning) is widely used by tour operators to attract target species,
      facilitate viewing and interaction with tourists. Although potential effects of
      such provisioning on terrestrial fauna have been given moderate scientific
      research attention, equivalent research in the marine environment is limited.
      Effects of provisioning marine wildlife may include direct habituation,
      behavioural change, and/or dietary impacts among individuals and species. There
      may also be disruption to the species associated assemblage. It was found that
      the literature on the effects of non-consumptive wildlife tourism is fragmented
      and results from different areas and taxa are frequently contradictory. Most
      studies appeared to be of a few years duration, at most. This reflects the
      relative immaturity of the industry - many enterprises studied typically
      commenced within the 1990 s. Studies (other than fish) tended to focus on a focal
      species with few addressing the wider implications for the associated assemblage.
      Supplementary feeding may also have impacts on the health and wellbeing of
      provisioned animals. It is concluded that such nature tourism is often not benign
      - focal species and their assemblage are often disrupted. We conclude that
      funding to better understand the impacts and thus address them is imperative. To
      supplement funding for the research and monitoring required, an additional charge
      could incorporated into the fee charged to those engaging in marine wildlife
      tourism.

PMID- 25576699
TI  - Anodal transcranial direct current stimulation (tDCS) increases frontal-midline
      theta activity in the human EEG: a preliminary investigation of non-invasive
      stimulation.
AB  - Rhythmical brain activity in the range between four and eight Hz acquired over
      frontal-midline EEG recording sites - so called frontal-midline theta activity -
      is regarded as one of the most prominent neural signatures of sustained
      attention. It is reported to parametrically increase with cognitive load and is
      thought to be generated in medial prefrontal cortex. Here we explored the
      possibility of using anodal transcranial direct current stimulation over frontal
      sites to enhance frontal-midline theta activity and to increase sustained
      attention performance. We used a small preliminary sample to test a novel direct
      current stimulation electrode configuration by which we were able to
      significantly increase frontal-midline theta amplitude in a resting condition
      after the end of the stimulation period. Using standardised low resolution
      electromagnetic tomography analysis the effect in the surface EEG was localised
      to right prefrontal and left medial prefrontal brain areas. Transcranial direct
      current stimulation did, however, not have any impact on behavioural performance
      during a sustained attention task. This most likely was due to a very fast
      washout of the stimulation's after effect on theta activity. Although these are
      only preliminary results from a rather small sample, this study demonstrates that
      transcranial direct current stimulation can be used to rather selectively enhance
      frontal-midline theta amplitude. 

PMID- 25576700
TI  - The role of hepcidin in chronic mild stress-induced depression.
AB  - Depression is one of the most prevalent challenges of mental conditions. Yet its
      exact etiology has not been clear. Chronic stress increases the production of
      cytokines, which can lead to depression. Hepcidin, an iron modulator, is involved
      in the inflammation process as well as iron homeostasis. This study was designed
      to investigate the role of hepcidin, on stress-induced depression. 60 male wistar
      rats were entered the experiment. We used a chronic unpredictable mild stress
      (for 28 days) as a rat model of depression. In stressed group, three subgroups
      were treated with three different doses of dalteparin (a hepcidin inhibitor):
      70IU/kg, 100IU/kg and 140IU/kg daily, for 4 weeks. The animals in the stressed
      group had more depressive-like behavior than the control group. Moreover, chronic
      mild stress produced an increased serum interleukin-6 levels. These effects were
      accompanied by an obvious increase in hepcidin mRNA level and iron content in the
      hippocampus. These changes were blocked by the injection of dalteparin. In
      conclusion, inhibition of hepcidin may reduce many pathological changes seen in
      stress-induced depressive disorders. 

PMID- 25576701
TI  - The protective effects of urocortin1 against intracerebral hemorrhage by
      activating JNK1/2 and p38 phosphorylation and further increasing VEGF via
      corticotropin-releasing factor receptor 2.
AB  - Urocortin (UCN) has exhibited antiinflammatory and neuroprotective effects on
      intracerebral hemorrhage (ICH). However, the underlying mechanisms are still not
      clear. Therefore, this study was aimed to investigate effects of UCN1 on ICH in
      vitro and in vivo and further explore the possible mechanism. ICH was induced by
      an infusion of autologous blood into the unilateral striatum of anesthetized male
      Sprague-Dawley rats. The rats were randomly divided into three groups (8 rats per
      group): sham ICH control group, ICH saline group and ICH UCN1 group. UCN1 was
      infused into the lateral ventricle after 1h post-ICH. Neurological deficits were
      evaluated by modified neurological severity score (mNSS). Brain edema was
      assessed using the dry/wet method. The neurological cell metabolic activity of
      N2a and SH-SY5Y was detected by CCK-8. The level of VEGF, JNK and p38 were
      determined by enzyme-linked immunosorbent assay and western blot. Post-treatment
      with UCN1 could improve neurological deficits and reduce brain edema. Moreover,
      UCN1 could increase the metabolic activity of neuron cells dose-dependently and
      these effects could be abolished by corticotropin-releasing factor receptor 2
      (CRFR2) antagonist anti-Svg-30. Furthermore, the level of VEGF, JNK and p38 were
      up-regulated by post-treatment with UCN1 via CRFR2. The protective effects of
      UCN1 against ICH are possibly mediated by activating the phosphorylation of JNK
      and p38 and further increasing the level of VEGF via CRFR2. 

PMID- 25576702
TI  - Corticosterone increases intracellular Zn(2+) release in hippocampal HT-22 cells.
AB  - The previous studies suggested that the hippocampal zinc dyshomeostasis and high
      glucocorticoid level might hurt hippocampal function. However, the effect of
      corticosterone (CORT) on hippocampus zinc homeostasis is not fully characterized.
      In this study, we investigated the intracellular Zn(2+) concentration in
      hippocampal HT-22 cells after CORT treatment. The cells were incubated with 10MUM
      CORT for 0h-24h, 0MUM-50MUM CORT for 6h and 2.5MUM glucocorticoid receptor
      antagonist RU486 administered 30min before CORT application. The results showed
      that 10MUM CORT increased the intracellular Zn(2+) level after 6h, which was
      diminished by 2.5MUM RU486. Co-treatment of ZnSO4 and CORT augmented the increase
      in Zn(2+) level. TPEN, a membrane-permeable chelator for intracellular Zn(2+)
      greatly attenuated the Zn(2+) increase by CORT, while DTPA, a chelator for
      extracellular Zn(2+), had no same effects. CCK-8 tests demonstrated that 10MUM
      CORT treatment for 6h had no inhibition effect on cells. However, intracellular
      reactive oxygen species (ROS) production increased and adenosine triphosphate
      (ATP) level decreased significantly after same CORT treatment, which was
      corrected by TPEN and aggravated by ZnSO4. It could be suggested that the
      increased intracellular Zn(2+) by CORT was greatly dependent on intracellular
      Zn(2+) release, but not extracellular Zn(2+) intake. Meanwhile, our results
      demonstrated that increased intracellular Zn(2+) by CORT resulted in ROS
      generation and decreased ATP level in cells, which have possible roles in the
      hippocampal function disorder induced by stress. 

PMID- 25576703
TI  - Potential involvement of the mitochondrial unfolded protein response in
      depressive-like symptoms in mice.
AB  - Many evidences strongly suggest that a mitochondrial deficit is implicated in
      major depression. A mitochondrial deficit leads to mitochondrial stress
      responses, including the mitochondrial unfolded protein response (UPRmt), which
      is associated with certain brain disorders such as spastic paraplegia and
      Parkinson's disease. However, there is no evidence regarding the relationship
      between depressive disorder and UPRmt. Mice treated with chronic restraint stress
      showed significant depressive-like behaviors in the tail suspension and forced
      swim tests, decreased oxygen consumption rate, and increased levels of molecules
      associated with UPRmt such as Hspa9, Hspd1, Ubl5, Abcb10, and ClpP. All of the
      UPRmt-related molecules were significantly correlated with depressive-like
      behavior in the forced swim test. Thus, the present study is to reveal a
      relationship between the UPRmt and depressive disorder, suggesting that the UPRmt
      is a potential drug target for depressive disorders. 

PMID- 25576705
TI  - Enhanced calcium responses to serotonin receptor stimulation in T-lymphocytes
      from schizophrenic patients--a pilot study.
AB  - Even if more extensively investigated in affective disorders, the serotonergic
      system is likely to be also implicated in modulating the pathogenesis of
      schizophrenia, where it closely interacts with the dopaminergic and glutamatergic
      system. To substantiate this notion, we studied the intensity and dynamics of
      cellular Ca(2+) responses to serotonin (5-hydoxytryptamine, 5-HT) in peripheral
      lymphocytes taken from currently non-psychotic schizophrenic patients. To this
      aim, peripheral lymphocytes were freshly obtained from healthy controls and a
      naturalistic collective of patients with schizophrenia in remission.
      Intracellular Ca(2+) responses were recorded in real-time by ratiometric
      fluorometry after 5-HT or phythaemagglutinin (PHA) stimulation, which served as
      an internal reference for Ca(2+) responsivity to non-specific stimulation. The
      intracellular Ca(2+) peak early after applying the 5-HT trigger was significantly
      elevated in schizophrenic patients. No significant differences of Ca(2+) peak
      levels were seen in response to stimulation with the mitogenic agent PHA,
      although responses to 5-HT and PHA were positively correlated in individual
      patients or controls. In conclusion, the serotonergic response patterns in
      peripheral lymphocytes from schizophrenic patients seem to be elevated, if
      employing sensitive tools like determination of intracellular Ca(2+) responses.
      Our observations suggest that the participation of serotonergic neurotransmitter
      system in the pathogenesis of schizophrenia may deserve more interest, even if it
      should only act as a modulator on the main pathology in the dopaminergic and
      glutamatergic systems. We hope that this pilot study will prompt further studies
      with larger patient collectives to revisit this question. 

PMID- 25576704
TI  - Apolipoprotein 4 may increase viral load and seizure frequency in mesial temporal
      lobe epilepsy patients with positive human herpes virus 6B.
AB  - This study investigated whether apolipoprotein 4 (ApoE4) was associated with the
      presence of human herpes virus (HHV)-6B in mesial temporal lobe epilepsy (MTLE).
      Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) was
      used to determine ApoE polymorphism in 46 patients with MTLE and 19 controls.
      Nested PCR and real-time PCR were applied to determine HHV-6B DNA and
      immunohistochemistry (IHC) for HHV-6B protein. Viral DNA load was significantly
      increased in MTLE patients with HHV-6B(+)/ApoE4 compared with those with HHV
      6B(+)/non-ApoE4 (p=0.031). Semi-quantitative analysis of IHC showed significantly
      increased number of positive cells for HHV-6B proteins G116/64/54, P98 and U94 in
      patients with HHV-6B(+)/ApoE4 than HHV-6B(+)/non-ApoE4 (p=0.009, 0.035 and 0.009,
      respectively). Patients with HHV-6B(+)/ApoE4 showed higher seizure frequency than
      those with HHV-6B(+)/non-ApoE4 (p=0.005). There was no significant difference of
      ApoE alleles between MTLE with and without HHV-6B (p=0.115). ApoE4 was not
      associated with initial infection of HHV-6B in MTLE. However, ApoE4 may
      facilitate HHV-6B reactivation, DNA replication, virus protein expression and
      increase seizure frequency in MTLE. Further investigations are needed to
      understand the biomolecular mechanism underlying interaction between ApoE and HHV
      6B. 

PMID- 25576707
TI  - Blood pressure level profiles among obese children and adolescents with different
      stature.

PMID- 25576706
TI  - Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central
      renin-angiotensin system in 1alpha(OH)ase knockout mice.
AB  - Previously, we reported that active vitamin D deficiency in mice causes secondary
      hypertension and cardiac dysfunction, but the underlying mechanism remains
      largely unknown. To clarify whether exogenous active vitamin D rescues
      hypertension by normalizing the altered central renin-angiotensin system (RAS)
      via an antioxidative stress mechanism, 1-alpha-hydroxylase [1alpha(OH)ase]
      knockout mice [1alpha(OH)ase(-/-)] and their wild-type littermates were fed a
      normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high
      calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l
      cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type
      littermates, 1alpha(OH)ase(-/-)mice had high mean arterial pressure, increased
      levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and
      increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV
      proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione
      peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these
      pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus
      rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3
      normalizes the altered central RAS in 1alpha(OH)ase(-/-)mice, at least partially,
      through a central antioxidative mechanism. 

PMID- 25576708
TI  - Does Trastuzumab cause permanent severe mitral regurgitation?

PMID- 25576709
TI  - Anomalous single coronary artery (R-type) in the elderly: description of benign
      and isolated variant.

PMID- 25576710
TI  - Prevalence of atrial fibrillation and its risk factors in rural China: a cross
      sectional study.
AB  - OBJECTIVES: To evaluate the prevalence of atrial fibrillation (AF) in physical
      laborers in rural China and identify contributing risk factors. METHODS: A cross
      sectional study of 11,956 permanent residents of Liaoning Province in rural
      China>=35y of age (primarily physical laborers) was conducted between January and
      August 2013 (response rate 85.3%). All participants completed a questionnaire and
      underwent a physical exam, echocardiography and electrocardiography. Blood
      samples were drawn for laboratory analyses, and AF was diagnosed on the basis of
      history and electrocardiograph findings. Risk factors for AF were evaluated with
      a stepwise logistic regression analysis. RESULTS: The prevalence of AF was 1.2%
      overall, but rose steeply with age (0.1% in those 35-44y of age, and 4.6% in
      those>=75y); there was no significant gender difference at any age. Independent
      risk factors for AF were age (odds ratio [OR] 1.89; P<0.001), diabetes (OR 2.07;
      P=0.001), history of myocardial infarction (OR 5.91; P<0.001), low left
      ventricular ejection fraction (OR 1.85; P=0.005), and low physical activity (OR
      1.72; P=0.003), whereas obesity, hypertension, cholesterol and triglyceride
      levels, current smoking and drinking, left ventricular hypertrophy, and family
      history of AF were not significant contributors. CONCLUSIONS: Although the
      prevalence of AF in physical labors in rural China is low, age, diabetes, history
      of myocardial infarction, low left ventricular ejection fraction, and low
      physical activity are independent risk factors.

PMID- 25576712
TI  - Variations in afferent conduction and axonal morphometrics of aortic depressive
      nerve imply wider baroreflex function of low-threshold and sex-specific
      myelinated Ah-type baroreceptor neurons in rats.

PMID- 25576711
TI  - QTc interval prolongation in systemic sclerosis: correlations with clinical
      variables.

PMID- 25576713
TI  - On the quest of unraveling the pathophysiology of Takotsubo syndrome.

PMID- 25576714
TI  - Genetic screening for the detection of a rare form of cardiomyopathy in a young
      patient with recurrent syncopes.

PMID- 25576715
TI  - Deficiency of creatine kinase in a ST-segment elevation myocardial infarction
      patient with Kartagener syndrome.

PMID- 25576716
TI  - Left ventricular structure and function among sisters of peripartum
      cardiomyopathy patients.

PMID- 25576717
TI  - Prompt and accurate diagnosis of ventricular arrhythmias with a novel index based
      on phase space reconstruction of ECG.
AB  - AIM: To develop a statistical index based on the phase space reconstruction (PSR)
      of the electrocardiogram (ECG) for the accurate and timely diagnosis of
      ventricular tachycardia (VT) and ventricular fibrillation (VF). METHODS: Thirty
      two ECGs with sinus rhythm (SR) and 32 ECGs with VT/VF were analyzed using the
      PSR technique. Firstly, the method of time delay embedding were employed with the
      insertion of delay "tau" in the original time-series X(t), which produces the
      Y(t)=X(t-tau). Afterwards, a PSR diagram was reconstructed by plotting Y(t)
      against X(t). The method of box counting was applied to analyze the behavior of
      the PSR trajectories. Measures as mean (MU), standard deviation (sigma) and
      coefficient of variation (CV=sigma/MU), kurtosis (beta) for the box counting of
      PSR diagrams were reported. RESULTS: During SR, CV was always <0.05, while with
      the onset of arrhythmia CV increased >0.05. A similar pattern was observed with
      beta, where <6 was considered as the cut-off point between SR and VT/VF.
      Therefore, the upper threshold for SR was considered CVth=0.05 and betath<6. For
      optimisation of the accuracy, a new index (J) was proposed: J=wCVCVth+1
      wbetabetath. During SR the upper limit of J was the value of 1. Furthermore CV,
      beta and J crossed the cut-off point timely before the onset of arrhythmia
      (average time: 4min 31s; SD: 2min 30s); allowing sufficient time for preventive
      therapy. CONCLUSION: The J index improved ECG utility for arrhythmia monitoring
      and detection utility, allowing the prompt and accurate diagnosis of ventricular
      arrhythmias.

PMID- 25576718
TI  - Recovery of absence seizure-like symptoms in a patient after slow pathway
      radiofrequency ablation.

PMID- 25576719
TI  - Necessity of epicardial ablation for ventricular tachycardia after sequential
      endocardial approach.
AB  - BACKGROUND: Catheter ablation (CA) of ventricular tachycardia (VT) is an
      important treatment option in patients with structural heart disease (SHD) and
      implantable cardioverter defibrillator (ICD). A subset of patients requires
      epicardial CA for VT. OBJECTIVE: The purpose of the study was to assess the
      significance of epicardial CA in these patients after a systematic sequential
      endocardial approach. METHODS: Between January 2009 and October 2012 CA for VT
      was analyzed. A sequential CA approach guided by earliest ventricular activation,
      pacemap, entrainment and stimulus to QRS-interval analysis was used. Acute CA
      success was assessed by programmed ventricular stimulation. ICD interrogation and
      24h-Holter ECG were used to evaluate long-term success. RESULTS: One hundred
      sixty VT ablation procedures in 126 consecutive patients (114 men; age 65+/
      12years) were performed. Endocardial CA succeeded in 250 (94%) out of 265 treated
      VT. For 15 (6%) VT an additional epicardial CA was performed and succeeded in 9
      of these 15 VT. Long-term FU (25+/-18.2month) showed freedom of VT in 104 pts
      (82%) after 1.2+/-0.5 procedures, 11 (9%) suffered from repeated ICD shocks and
      11 (9%) died due to worsening of heart failure. CONCLUSIONS: Despite a
      heterogenic substrate for VT in SHD, endocardial CA alone results in high acute
      success rates. In this study additional epicardial CA following a sequential
      endocardial mapping and CA approach was performed in 6% of VT. Thus, due to
      possible complications epicardial CA should only be considered if endocardial CA
      fails.

PMID- 25576720
TI  - Unity is strength - a panel of 4 microRNAs decreases cardiomyocyte hypertrophy.

PMID- 25576721
TI  - Incidence of acute kidney injury in reported cases of lead related cardiac
      perforation.

PMID- 25576722
TI  - Health-related quality of life five years after coronary artery bypass graft
      surgery.

PMID- 25576723
TI  - Prognostic value of ventricular heart rate in patients with permanent atrial
      fibrillation and heart failure.

PMID- 25576724
TI  - Percutaneous transaortic valve implantation for severe aortic regurgitation in a
      patient with a porto-pulmonary hypertension.

PMID- 25576725
TI  - Prognostic value of in-hospital change in cystatin C in patients with acutely
      decompensated heart failure and renal dysfunction.

PMID- 25576726
TI  - Muscle squeezing of the culprit coronary artery in a patient with ST-elevation
      myocardial infarction after postconditioning with lactate-enriched blood.

PMID- 25576727
TI  - Adjunct coronary endarterectomy increases cerebrovascular accident after coronary
      artery bypass grafting: a meta-analysis of 17,600 patients.

PMID- 25576728
TI  - A single centre retrospective cohort study to evaluate the association between
      implementation of an acute myocardial infarction clinical pathway and clinical
      outcomes.

PMID- 25576729
TI  - Use of different types of angiotensin converting enzyme inhibitors and mortality
      in systolic heart failure.
AB  - BACKGROUND: Angiotensin converting enzyme-inhibitors (ACEIs) are the first-line
      treatment for patients with heart failure (HF) with reduced ejection fraction
      (EF). The benefit of ACEIs in HF is regarded as a class effect and different
      types of agents are used interchangeably. However, evidence on the comparable
      effectiveness of different ACEIs is scarce. We conducted a registry-based cohort
      study to assess all-cause mortality associated with the use of enalapril,
      perindopril, and trandolapril, as compared with ramipril, in patients with
      systolic HF. METHODS: Patients with systolic HF (EF <=40%), 2003-2012, were
      identified using the Danish HF Registry. New users of enalapril (n=1807),
      perindopril (n=1064), ramipril (n=3270), or trandolapril (n=1150), who started
      treatment within 60days of first-time hospital diagnosis of HF, were selected for
      inclusion. Subgroup analyses were conducted by sex, age, NYHA-level, EF, and
      ischemic heart disease. All analyses were adjusted for empirical risk scores for
      mortality. RESULTS: During follow-up, 291 deaths were observed among users of
      enalapril (incidence rate per 100person-years [IR], 10.1), 212 among users of
      perindopril (IR, 10.5), 568 among users of ramipril (IR, 10.6), and 251 among
      users of trandolapril (IR, 12.1). No significant differences in all-cause
      mortality were observed with the use of enalapril (adjusted hazard ratio [aHR]
      0.95, 95% CI 0.82-1.10), perindopril (aHR 1.07, 95% CI 0.92-1.26), or
      trandolapril (aHR 1.08, 95% CI 0.93-1.26), as compared with ramipril. No
      significant differences were observed in subgroup analyses. CONCLUSIONS: These
      findings suggest equal effect of different types of ACEIs on mortality in
      systolic HF.

PMID- 25576731
TI  - People with pain were less likely to learn to live with disease symptoms: Welsh
      Health Survey, 2012.

PMID- 25576730
TI  - Modified Potts shunt in an adult with pulmonary arterial hypertension and
      recurrent syncope - three-year follow-up.

PMID- 25576732
TI  - One incision, two cannulations for minimally invasive aortic valve surgery.

PMID- 25576733
TI  - Hepsin inhibits CDK11p58 IRES activity by suppressing unr expression and eIF
      2alpha phosphorylation in prostate cancer.
AB  - Hepsin is a type II transmembrane serine protease frequently overexpressed in
      prostate cancer (PCa). However, the role of hepsin in PCa remains unclear. In
      this study, we found that hepsin inhibited the internal ribosome entry site
      (IRES) activity and expression of CDK11p58, which is associated with cell cycle
      progression and pro-apoptotic signaling in PCa. Hepsin suppressed CDK11p58 IRES
      activity in PCa by modulating unr expression and eIF-2alpha phosphorylation.
      Further studies revealed that hepsin inhibited the expression of unr by directly
      binding to unr IRES element and suppressing its activity, and also repressed eIF
      2alpha phosphorylation through down-regulating the expression and phosphorylation
      of general control non-derepressible-2 (GCN2). Taken together, our data suggest a
      novel role of hepsin in regulating CDK11p58 IRES activity, and imply that hepsin
      may act on the machinery of translation to modulate cell cycle progression and
      survival in PCa cells.

PMID- 25576734
TI  - Calibration-free quantification of interior properties of porous media with x-ray
      computed tomography.
AB  - A method is presented for interpreting the values of x-ray attenuation
      coefficients reconstructed in computed tomography of porous media, while
      overcoming the ambiguity caused by the multichromatic nature of x-rays, dilution
      by void, and material heterogeneity. The method enables determination of porosity
      without relying on calibration or image segmentation or thresholding to
      discriminate pores from solid material. It distinguishes between solution
      accessible and inaccessible pores, and provides the spatial and frequency
      distributions of solid-matrix material in a heterogeneous medium. This is
      accomplished by matching an image of a sample saturated with a contrast solution
      with that saturated with a transparent solution. Voxels occupied with solid
      material and inaccessible pores are identified by the fact that they maintain the
      same location and image attributes in both images, with voxels containing
      inaccessible pores appearing empty in both images. Fully porous and accessible
      voxels exhibit the maximum contrast, while the rest are porous voxels containing
      mixtures of pore solutions and solid. This matching process is performed with an
      image registration computer code, and image processing software that requires
      only simple subtraction and multiplication (scaling) processes. The process is
      demonstrated in dolomite (non-uniform void distribution, homogeneous solid
      matrix) and sandstone (nearly uniform void distribution, heterogeneous solid
      matrix) samples, and its overall performance is shown to compare favorably with a
      method based on calibration and thresholding. 

PMID- 25576735
TI  - Analysis of JSI TRIGA MARK II reactor physical parameters calculated with TRIPOLI
      and MCNP.
AB  - New computational model of the JSI TRIGA Mark II research reactor was built for
      TRIPOLI computer code and compared with existing MCNP code model. The same
      modelling assumptions were used in order to check the differences of the
      mathematical models of both Monte Carlo codes. Differences between the TRIPOLI
      and MCNP predictions of keff were up to 100pcm. Further validation was performed
      with analyses of the normalized reaction rates and computations of kinetic
      parameters for various core configurations. 

PMID- 25576736
TI  - Effects of engineered iron nanoparticles on the bryophyte, Physcomitrella patens
      (Hedw.) Bruch & Schimp, after foliar exposure.
AB  - The effects of iron nanoparticles on bryophytes (Physcomitrella patens) were
      studied following foliar exposure. We used iron nanoparticles (Fe-NP)
      representative of industrial emissions from the metallurgical industries. After a
      characterization of iron nanoparticles and the validation of nanoparticle
      internalization in cells, the effects (cytotoxicity, oxidative stress, lipid
      peroxidation of membrane) of iron nanoparticles were determined through the
      axenic culturing of Physcomitrella patens exposed at five different
      concentrations (5 ng, 50 ng, 500 ng, 5 ug and 50 ug per plant). Following
      exposure, the plant health, measured as ATP concentrations, was not impacted.
      Moreover, we studied oxidative stress in three ways: through the measure of
      reactive oxygen species (ROS) production, through malondialdehyde (MDA)
      production and also through glutathione regulation. At concentrations tested over
      a short period, the level of ROS, MDA and glutathione were not significantly
      disturbed.

PMID- 25576737
TI  - Improving conversion yield of fermentable sugars into fuel ethanol in 1st
      generation yeast-based production processes.
AB  - Current fuel ethanol production using yeasts and starch or sucrose-based
      feedstocks is referred to as 1st generation (1G) ethanol production. These
      processes are characterized by the high contribution of sugar prices to the final
      production costs, by high production volumes, and by low profit margins. In this
      context, small improvements in the ethanol yield on sugars have a large impact on
      process economy. Three types of strategies used to achieve this goal are
      discussed: engineering free-energy conservation, engineering redox-metabolism,
      and decreasing sugar losses in the process. Whereas the two former strategies
      lead to decreased biomass and/or glycerol formation, the latter requires
      increased process and/or yeast robustness. 

PMID- 25576738
TI  - Antileishmanial activity of quinazoline derivatives: synthesis, docking screens,
      molecular dynamic simulations and electrochemical studies.
AB  - A series of quinazoline-2,4,6-triamine were synthesized and evaluated in vitro
      against Leishmania mexicana. Among them, N(6)-(ferrocenmethyl)quinazolin-2,4,6
      triamine (H2) showed activity on promastigotes and intracellular amastigotes, as
      well as low cytotoxicity in mammalian cells. Docking and electrochemical studies
      showed the importance of both the ferrocene and the heterocyclic nucleus to the
      observed activity. H2 is readily oxidized electrochemically, indicating that the
      mechanism of action probably involves redox reactions. 

PMID- 25576739
TI  - A novel series of thiazolyl-pyrazoline derivatives: synthesis and evaluation of
      antifungal activity, cytotoxicity and genotoxicity.
AB  - In the current work, new thiazolyl-pyrazoline derivatives (1-22) were synthesized
      and evaluated for their antifungal effects against pathogenic yeasts and molds
      using a broth microdilution assay. Ames assay was carried out to determine the
      genotoxicity of the most effective antifungal derivatives. The cytotoxicity of
      the compounds (1-22) was also investigated against A549 human lung adenocarcinoma
      and NIH/3T3 mouse embryonic fibroblast cells. Among these derivatives, 2-[5-(4
      fluorophenyl)-3-(5-methylthiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl]-4-(4
      methylsulfonylphenyl)thiazole (18) can be identified as the most promising
      anticandidal derivative due to its notable inhibitory effect on Candida
      zeylanoides with a MIC value of 250 MUg/mL when compared with ketoconazole (MIC =
      250 MUg/mL), low cytotoxicity against NIH/3T3 cells and non-mutagenic effect. On
      the other hand, 2-[5-(4-fluorophenyl)-3-(5-chlorothiophen-2-yl)-4,5-dihydro-1H
      pyrazol-1-yl]-4-(4-bromophenyl)thiazole (4) can be considered as the most
      promising anticancer agent against A549 cancer cells owing to its notable
      inhibitory effect on A549 cells with an IC50 value of 62.5 MUg/mL when compared
      with cisplatin (IC50 = 45.88 MUg/mL) and low cytotoxicity against NIH/3T3 cells. 

PMID- 25576740
TI  - Photocytotoxic oxovanadium(IV) complexes of ferrocenyl-terpyridine and
      acetylacetonate derivatives.
AB  - Oxovanadium(IV) complexes [VO(Fc-tpy)(acac)](ClO4) (1), [VO(Fc-tpy)(nap
      acac)](ClO4) (2), [VO(Fc-tpy)(py-acac)](ClO4) (3) and [VO(Ph-tpy)(py-acac)](ClO4)
      (4) of 4'-ferrocenyl-2,2':6',2"-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2"
      terpyridine (Ph-tpy) having monoanionic acetylacetonate (acac),
      naphthylacetylacetonate (nap-acac) or pyrenylacetylacetonate (py-acac) ligand
      were prepared, characterized and their photocytotoxicity in visible light
      studied. The ferrocenyl complexes 1-3 showed an intense charge transfer band near
      585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near 0.66 V
      and -0.95 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf
      thymus DNA showed significant photocleavage of plasmid DNA in green light (568
      nm) forming OH radicals. The complexes that are photocytotoxic in HeLa and MCF-7
      cancer cells in visible light (400-700 nm) with low dark toxicity remain nontoxic
      in normal fibroblast 3T3 cells. ICP-MS and fluorescence microscopic studies show
      significant cellular uptake of the complexes. Photo-irradiation of the complexes
      causes apoptotic cell death by ROS as evidenced from the DCFDA assay.

PMID- 25576741
TI  - Sulfated glycans in inflammation.
AB  - Sulfated glycans such as glycosaminoglycans on proteoglycans are key players in
      both molecular and cellular events of inflammation. They participate in leukocyte
      rolling along the endothelial surface of inflamed sites; chemokine regulation and
      its consequential functions in leukocyte guidance, migration and activation;
      leukocyte transendothelial migration; and structural assembly of the
      subendothelial basement membrane responsible to control tissue entry of cells.
      Due to these and other functions, exogenous sulfated glycans of various
      structures and origins can be used to interventionally down-regulate inflammation
      processes. In this review article, discussion is given primarily on the anti
      inflammatory functions of mammalian heparins, heparan sulfate, chondroitin
      sulfate, dermatan sulfate and related compounds as well as the holothurian
      fucosylated chondroitin sulfate and the brown algal fucoidans. Understanding the
      underlying mechanisms of action of these sulfated glycans in inflammation, helps
      research programs involved in developing new carbohydrate-based drugs aimed to
      combat acute and chronic inflammatory disorders. 

PMID- 25576742
TI  - Dietary ractopamine influences sarcoplasmic proteome profile of pork Longissimus
      thoracis.
AB  - Dietary ractopamine improves pork leanness, whereas its effect on sarcoplasmic
      proteome has not been characterized. Therefore, the influence of ractopamine on
      sarcoplasmic proteome of post-mortem pork Longissimus thoracis muscle was
      examined. Longissimus thoracis samples were collected from carcasses (24 h post
      mortem) of purebred Berkshire barrows (n=9) managed in mixed-sex pens and fed
      finishing diets containing ractopamine (RAC; 7.4 mg/kg for 14 days followed by
      10.0 mg/kg for 14 days) or without ractopamine for 28 days (CON). Sarcoplasmic
      proteome was analyzed using two-dimensional electrophoresis and mass
      spectrometry. Nine protein spots were differentially abundant between RAC and CON
      groups. Glyceraldehyde-3-phosphate dehydrogenase and phosphoglucomutase-1 were
      over-abundant in CON, whereas serum albumin, carbonic anhydrase 3, L-lactate
      dehydrogenase A chain, fructose-bisphosphate aldolase A, and myosin light chain
      1/3 were over-abundant in RAC. These results suggest that ractopamine influences
      the abundance of enzymes involved in glycolytic metabolism, and the differential
      abundance of glycolytic enzymes could potentially influence the conversion of
      muscle to meat.

PMID- 25576743
TI  - Microvascular blood flow monitoring with laser speckle contrast imaging using the
      generalized differences algorithm.
AB  - Laser speckle contrast imaging (LSCI) is a full-field optical technique to
      monitor microvascular blood flow with high spatial and temporal resolutions. It
      is used in many medical fields such as dermatology, vascular medicine, or
      neurosciences. However, LSCI leads to a large amount of data: image sampling
      frequency is often of several Hz and recordings usually last several minutes.
      Therefore, clinicians often perform regions of interest in which a spatial
      averaging of blood flow is performed and the result is followed with time.
      Unfortunately, this leads to a poor spatial resolution for the analyzed data. At
      the same time, a higher spatial resolution for the perfusion maps is wanted. To
      get over this dilemma we propose a new post-acquisition visual representation for
      LSCI perfusion data using the so-called generalized differences (GD) algorithm.
      From a stack of perfusion images, the procedure leads to a new single image with
      the same spatial resolution as the original images and this new image reflects
      perfusion changes. The algorithm is herein applied on simulated stacks of images
      and on experimental LSCI perfusion data acquired in three different situations
      with a commercialized laser speckle contrast imager. The results show that the GD
      algorithm provides a new way of visualizing LSCI perfusion data. 

PMID- 25576744
TI  - Spatial and seasonal heterogeneity of atmospheric particles induced reactive
      oxygen species in urban areas and the role of water-soluble metals.
AB  - Adverse health effects are associated with exposure to atmospheric particulate
      matter (PM), which carry various chemical constituents and induce both exogenous
      and endogenous oxidative stress. This study investigated the spatial and seasonal
      variability of PM-induced ROS at four sites with different characteristics in
      Hong Kong. Cytotoxicity, exogenous and endogenous ROS was determined on a dose
      and time dependent analysis. Large spatial variation of ROS was observed with
      fine PM at urban site showing highest ROS levels while coarse PM at traffic site
      ranks the top. No consistent seasonal difference was observed for ROS levels
      among all sites. The highly heterogeneous distribution of PM-induced ROS
      demonstrates the differential capability of PM to produce oxidative stress, and
      the need to use appropriate metrics as surrogates of exposure instead of PM mass
      in epidemiologic studies. Several transition metals were found associated with
      ROS by different degree illustrating the complexity of mechanisms involved. 

PMID- 25576745
TI  - Effect of different cross-linking methods and processing parameters on drug
      release from hydrogel beads.
AB  - The purpose of this work was to evaluate different methods of cross-linking for
      developing diltiazem-resin complex loaded carboxymethyl xanthan gum (CMXG)
      hydrogel beads to achieve highest possible drug entrapment and extended release
      for effective cardio-protection. The hydrogel beads were prepared by ionic cross
      linking and dual cross-linking using simultaneous (SIM) and sequential (SEQ)
      methods. Among the three methods, SEQ method produced smaller sized beads having
      higher drug entrapment efficacy and prolonged release characteristics as
      evidenced from mean dissolution time and diffusion coefficient of drug. Keeping
      the concentration of ionic cross-linker constant, increase in the amount of
      covalent cross-linker and cross-linking time decreased the drug release. Higher
      release of the drug in acid solution was attributed to the higher solubility of
      the basic drug and higher swelling of the matrices in acid solution. Comparison
      of FTIR spectra, drug content and dissolution profiles indicated that the drug
      was stable in the beads when kept under stress condition up to 3 months. In
      conclusion, the sequential method was found superior for producing CMXG hydrogel
      beads as a prolonged release delivery device in cardiovascular diseases. 

PMID- 25576746
TI  - Synthesis and characterization of water-soluble chitosan grafted with hydrophilic
      aliphatic polyester.
AB  - Traditionally, hydrophobic aliphatic polyester has been employed to modify
      chitosan and organic soluble or swellable graft copolymers have been obtained. In
      this work, linear poly(butylene tartrate) (PBT) with hydrophilic pendant hydroxyl
      groups, which was synthesized by direct polycondensation of tartaric acid and
      butanediol under mild condition, was chosen to modify chitosan and synthesize PBT
      grafted chitosan (CS-g-PBT) with the mediation of 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide in aqueous solution of an ionic liquid. The
      chain length of the grafted PBT could be facilely controlled by varying the
      molecular weight of PBT. The chemical structures of CS-g-PBT were systematically
      characterized by 1H NMR, attenuated total reflectance Fourier transform infrared
      and wide-angle X-ray diffraction. The thermal properties were investigated by
      thermogravimetric analysis and differential scanning calorimetry. The water
      solubility of chitosan has been effectively improved after grafting with PBT and
      a water-soluble chitosan derivative has been synthesized. Meanwhile, the water
      solubility of grafts varies regularly with chain length of grafted PBT.

PMID- 25576748
TI  - From the Editor-in-Chief.

PMID- 25576747
TI  - Biorefineries for the production of top building block chemicals and their
      derivatives.
AB  - Due to the growing concerns on the climate change and sustainability on
      petrochemical resources, DOE selected and announced the bio-based top 12 building
      blocks and discussed the needs for developing biorefinery technologies to replace
      the current petroleum based industry in 2004. Over the last 10 years after its
      announcement, many studies have been performed for the development of efficient
      technologies for the bio-based production of these chemicals and derivatives.
      Now, ten chemicals among these top 12 chemicals, excluding the l-aspartic acid
      and 3-hydroxybutyrolactone, have already been commercialized or are close to
      commercialization. In this paper, we review the current status of biorefinery
      development for the production of these platform chemicals and their derivatives.
      In addition, current technological advances on industrial strain development for
      the production of platform chemicals using micro-organisms will be covered in
      detail with case studies on succinic acid and 3-hydroxypropionic acid as
      examples. 

PMID- 25576749
TI  - The health workforce crisis in Pakistan: a critical review and the way forward.
AB  - Today, the developing world suffers due to the health "workforce crisis." The
      World Health Report 2006 uses this term to study the current scenario in the
      developing countries. Human resource planning is a critical activity within the
      broader sectoral planning, especially when it comes to the health sector.
      Pakistan faces an acute shortage of different cadres of healthcare workers, which
      is bound to escalate further because of the high population growth rate,
      inequitable distribution and out-migration of the healthcare workforce. In the
      wake of ongoing reforms in the health sector of Pakistan, it is suggested that
      for the strengthening of health systems, there ought to be a serious thought
      process involved for developing a human resource plan for the health sector that
      responds to the needs of the population and the disease burden. A national
      strategy is imperative to retain, train and incentivize the health workforce. 

PMID- 25576750
TI  - Are non-critical medical devices potential sources of infections in healthcare
      facilities?
AB  - This paper reviewed studies that investigated the contamination of non-critical
      medical devices (NCMDs) and their potential as routes for nosocomial infection
      transmission. Using MEDLINE Entrez PubMed, relevant publications were identified
      using "nosocomial infections" in combination with each of the following:
      stethoscopes, ultrasound transducers, tourniquets, pens, scissors, white coats,
      thermometers, blood pressure cuffs, dermatoscopes and otoscopes. Of 258 studies
      identified, 51 fulfilled the study inclusion criteria and had sufficient
      information on microbiological assessment of the NCMDs. All the studies reported
      microbial contamination of NCMDs, with Staphylococcus species as the predominant
      contaminant. The studies reported that health workers rarely disinfect NCMDs
      between uses with different patients. Most studies recorded NCMD contamination
      rates ranging from 25% to 100%. Percentage contamination of NCMDs by methicillin
      resistant Staphylococcus aureus ranged from 2.3% to 32%. To reduce the
      possibility of a nosocomial infection transmission through contaminated NCMDs,
      disinfection of NCMDs before using them on each patient must be strictly adhered
      to. 

PMID- 25576752
TI  - Systematic review of health-related quality of life measures for inflammatory
      bowel disease.
AB  - BACKGROUND AND AIM: Several measures have been developed to assess the health
      related quality of life [HRQoL] of patients with inflammatory bowel disease
      [IBD]. Our aim is to systematically review the HRQoL measures specific for
      patients with IBD and to appraise their measurement properties and methodological
      quality. METHODS: We searched the PubMed, Embase, and PsycINFO databases for
      original articles describing the development and/or evaluation of one or more of
      the measurement properties [e.g. internal consistency, reliability, validity,
      responsiveness] of HRQoL measures specific for IBD. We assessed the measurement
      properties and examined the methodological quality of the measurement properties
      of each instrument using a standardized checklist. RESULTS: We examined the full
      text of 75 articles that we deemed potentially eligible and identified 10 disease
      specific HRQoL measures in IBD that covered different aspects of patients' lives.
      Internal consistency, construct validity, and content validity were the commonly
      evaluated measurement properties. Seven HRQoL measures scored positive for at
      least four of eight measurement properties. The majority of studies were rated as
      'fair' to 'poor' when assessing their methodology quality. The most established
      HRQoL measure in the literature was the Inflammatory Bowel Disease Questionnaire
      [IBDQ]. CONCLUSIONS: Most of the included HRQoL measures did not include all the
      required measurement properties or had a problem with their methodological
      quality. The most widely used and validated measure was the IBDQ. Further
      validation studies are required to support the use of other HRQoL measures.

PMID- 25576753
TI  - Changes in serum trough levels of infliximab during treatment intensification but
      not in anti-infliximab antibody detection are associated with clinical outcomes
      after therapeutic failure in Crohn's disease.
AB  - BACKGROUND AND AIMS: Intensification of the infliximab (IFX) regimen is
      recommended if the treatment effect is inadequate. However, the rationale for
      this is not well defined as the underlying mechanisms vary. The aim of this study
      was to explore the association between changes in serum IFX and anti-IFX
      antibodies (Abs) after IFX intensification and clinical outcomes. METHODS: We
      performed a post hoc analysis of a randomized clinical trial including 42 Crohn's
      disease patients with IFX treatment failure, all treated with an intensified IFX
      regimen (5mg/kg every 4 week) for 12 weeks. Trough serum IFX and anti-IFX Ab
      concentrations were measured by a homogeneous mobility shift binding assay (HMSA)
      and a functional cell-based reporter gene assay (RGA) at treatment failure and
      the end of the trial. RESULTS: Twenty-one patients (50%) regained clinical
      response on the intensified IFX regimen. The increase in serum trough levels of
      IFX during treatment intensification was higher among responders than non
      responders (RGA, 8.8 versus 3.0 MUg/mL, p = 0.035; HMSA, 9.9 versus 4.7 MUg/mL, p
      = 0.040), and differentiated patients by clinical outcome (RGA, area under
      receiver operating characteristic curve [AUC] 0.75 [0.53-0.97], p = 0.035; HMSA,
      AUC 0.74 [0.53-0.95], p = 0.042). All responders exhibited an IFX increase >=2.6
      MUg/mL (sensitivity 100%, specificity 50%). Anti-IFX Abs detected by HMSA in 13
      patients (32%) were often non-functional and became undetectable during IFX
      intensification. However, even functional anti-IFX Abs detected by RGA in six
      patients (15%) became undetectable. CONCLUSION: Increase in IFX levels following
      treatment intensification was associated with improved clinical outcomes,
      indicating insufficient drug levels in a subgroup of patients. Anti-IFX Abs may
      become undetectable during treatment intensification, suggesting lowered
      production or the formation of immune complexes.

PMID- 25576754
TI  - Intrapartum corticosteroid use significantly increases the risk of gestational
      diabetes in women with inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Women with inflammatory bowel disease (IBD) may be at higher
      risk of adverse pregnancy outcomes. This study compared perinatal outcomes in
      women with and without IBD. METHODS: The population-based Data Integration,
      Measurement, and Reporting (DIMR) administrative discharge database was used to
      identify women (>=18 years of age) in Alberta, Canada, with IBD who delivered a
      baby between 2006 and 2009 inclusive. Women without IBD were randomly sampled and
      matched in a 3:1 ratio to IBD cases by age at conception (+/-1 year). Odds ratios
      of gestational diabetes, preterm birth, low birth weight, cesarean section, and
      neonatal intensive care unit admission were calculated. RESULTS: One hundred and
      sixteen IBD patients were age-matched to 381 pregnant women without IBD.
      Gestational diabetes, preterm birth, and cesarean section were more common in
      women with IBD compared with controls (6.9 versus 1.8%, p = 0.03; 12.9 versus
      0.3%, p < 0.0001; 43.1 versus 21.0%, p = 0.009, respectively). On multivariate
      analysis, women with IBD were independently more likely to have gestational
      diabetes (odds ratio [OR] = 4.3; 95% confidence interval [CI] 1.2-16.3), preterm
      birth (OR = 19.7, 95% CI 2.2-173.9), and to deliver by cesarean section (OR =
      2.7, 95% CI 1.6-4.6) after adjusting for age and smoking status. CONCLUSION:
      Intrapartum corticosteroid use significantly increases the risk of gestational
      diabetes in women with IBD. Furthermore, IBD patients are at higher risk of
      preterm delivery and are more likely to undergo cesarean section compared with a
      healthy age-matched population. The finding of a higher risk of gestational
      diabetes is a novel finding not previously reported in the IBD literature.

PMID- 25576755
TI  - Observed relationships between leaf H218O Peclet effective length and leaf
      hydraulic conductance reflect assumptions in Craig-Gordon model calculations.
AB  - Stable oxygen isotope techniques may be a useful tool to investigate the pathways
      of water movement within leaves. However, implementation of such methods is
      limited due to uncertainty in the effective path length (L) for the Peclet effect
      in leaf water enrichment models. Previous studies have found relationships
      between L and physiological parameters such as transpiration rate (E) and leaf
      hydraulic conductance (k(leaf)) both within and between species. However, these
      studies relied on assumptions in their calculation of L, which were not directly
      tested. Eucalyptus paniculata Smith was used to evaluate the relationships
      between L, k(leaf) and E under differing water availability and a range of leaf
      temperatures. Coupled gas exchange and transpiration isotope measurements allowed
      previous assumptions to be directly tested. L was significantly and negatively
      related to both k(leaf) and E when the isotopic signature of water vapour was
      assumed to be in equilibrium with source water, was equivalent to the room vapour
      or equal to source water. However, the relationship between L and k(leaf) was non
      significant when measured delta( 18)O of transpired vapour was used and
      disappeared entirely when non-steady-state leaves were excluded, and when
      evaporation site water was calculated from coupled gas exchange and transpiration
      isotope values. These results suggest that great care must be taken when
      calculating L, particularly regarding assumptions of isotopic steady state and
      delta( 18)O of vapour. Previous suggestions of changes in pathways for water
      movement as transpiration rate varied need to be reassessed in light of these
      observations.

PMID- 25576756
TI  - Distilling allometric and environmental information from time series of conduit
      size: the standardization issue and its relationship to tree hydraulic
      architecture.
AB  - Trees are among the best natural archives of past environmental information.
      Xylem anatomy preserves information related to tree allometry and
      ecophysiological performance, which is not available from the more customary ring
      width or wood-density proxy parameters. Recent technological advances make tree
      ring anatomy very attractive because time frames of many centuries can now be
      covered. This calls for the proper treatment of time series of xylem anatomical
      attributes. In this article, we synthesize current knowledge on the biophysical
      and physiological mechanisms influencing the short- to long-term variation in the
      most widely used wood-anatomical feature, namely conduit size. We also clarify
      the strong mechanistic link between conduit-lumen size, tree hydraulic
      architecture and height growth. Among the key consequences of these biophysical
      constraints is the pervasive, increasing trend of conduit size during ontogeny.
      Such knowledge is required to process time series of anatomical parameters
      correctly in order to obtain the information of interest. An appropriate
      standardization procedure is fundamental when analysing long tree-ring-related
      chronologies. When dealing with wood-anatomical parameters, this is even more
      critical. Only an interdisciplinary approach involving ecophysiology, wood
      anatomy and dendrochronology will help to distill the valuable information about
      tree height growth and past environmental variability correctly. 

PMID- 25576757
TI  - Morphological, biochemical and physiological traits of upper and lower canopy
      leaves of European beech tend to converge with increasing altitude.
AB  - The present work has explored for the first time acclimation of upper versus
      lower canopy leaves along an altitudinal gradient. We tested the hypothesis that
      restrictive climatic conditions associated with high altitudes reduce within
      canopy variations of leaf traits. The investigated beech (Fagus sylvatica L.)
      forest is located on the southern slope of the Hruby Jesenik Mountains (Czech
      Republic). All measurements were taken on leaves from upper and lower parts of
      the canopy of mature trees (>85 years old) growing at low (400 m above sea level,
      a.s.l.), middle (720 m a.s.l.) and high (1100 m a.s.l.) altitudes. Compared with
      trees at higher altitudes, those growing at low altitudes had lower stomatal
      conductance, slightly lower CO(2) assimilation rate (A(max)) and leaf mass per
      area (LMA), and higher photochemical reflectance index, water-use efficiency and
      Rubisco content. Given similar stand densities at all altitudes, the different
      growth conditions result in a more open canopy and higher penetration of light
      into lower canopy with increasing altitude. Even though strong vertical gradients
      in light intensity occurred across the canopy at all altitudes, lower canopy
      leaves at high altitudes tended to acquire the same morphological, biochemical
      and physiological traits as did upper leaves. While elevation had no significant
      effect on nitrogen (N) and carbon (C) contents per unit leaf area, LMA, or total
      content of chlorophylls and epidermal flavonoids in upper leaves, these increased
      significantly in lower leaves at higher altitudes. The increases in N content of
      lower leaves were coupled with similar changes in A(max). Moreover, a high N
      content coincided with high Rubisco concentrations in lower but not in upper
      canopy leaves. Our results show that the limiting role of light in lower parts of
      the canopy is reduced at high altitudes. A great capacity of trees to adjust the
      entire canopy is thus demonstrated.

PMID- 25576758
TI  - Patterns and variability in seedling carbon assimilation: implications for tree
      recruitment under climate change.
AB  - Predicting future forests' structure and functioning is a critical goal for
      ecologists, thus information on seedling recruitment will be crucial in
      determining the composition and structure of future forest ecosystems. In
      particular, seedlings' photosynthetic response to a changing environment will be
      a key component determining whether particular species establish enough
      individuals to maintain populations, as growth is a major determinant of
      survival. We quantified photosynthetic responses of sugar maple (Acer saccharum
      Marsh.), pignut hickory (Carya glabra Mill.), northern red oak (Quercus rubra L.)
      and eastern black oak (Quercus velutina Lam.) seedlings to environmental
      conditions including light habitat, temperature, soil moisture and vapor pressure
      deficit (VPD) using extensive in situ gas exchange measurements spanning an
      entire growing season. We estimated the parameters in a hierarchical Bayesian
      version of the Farquhar model of photosynthesis, additionally informed by soil
      moisture and VPD, and found that maximum Rubisco carboxylation (V(cmax)) and
      electron transport (J(max)) rates showed significant seasonal variation, but not
      the peaked patterns observed in studies of adult trees. Vapor pressure deficit
      and soil moisture limited J(max) and V(cmax) for all four species. Predictions
      indicate large declines in summer carbon assimilation rates under a 3  degrees C
      increase in mean annual temperature projected by climate models, while spring and
      fall assimilation rates may increase. Our model predicts decreases in summer
      assimilation rates in gap habitats with at least 90% probability, and with 20
      99.9% probability in understory habitats depending on species. Predictions also
      show 70% probability of increases in fall and 52% probability in spring in
      understory habitats. All species were impacted, but our findings suggest that oak
      species may be favored in northeastern North America under projected increases in
      temperature due to superior assimilation rates under these conditions, though as
      growing seasons become longer, the effects of climate change on seedling
      photosynthesis may be complex.

PMID- 25576759
TI  - First experiences with the Radial Reload with Tri-stapleTM technology in low
      rectal surgery.
AB  - INTRODUCTION: Low rectal surgery remains challenging. New surgical stapler
      devices have been developed to counteract problems of impaired visibility and
      inability to get low into the pelvis. One of them is the Radial Reload (RR) with
      Tri-staple(TM) Technology (Covidien, New Haven, CT, USA). The aim of this study
      was to assess the first impressions and experiences regarding handling of this
      new stapler device in low anterior resection procedures in living humans.
      METHODS: A questionnaire, consisting of 27 statements concerning accessibility,
      maneuverability and visibility, was sent to 35 surgeons worldwide. RESULTS: A
      total of 85 rectal surgical procedures, both open and laparoscopic, were assessed
      by 31 surgeons. In 97% of the procedures the surgeons agreed that the RR stapler
      device facilitated access in the low pelvis. The first stapler device firing
      achieved complete transection in 54% of the procedures. According to the
      surgeons' assessments, in 91% percent of the procedures the RR stapler device
      enabled creation of adequate margins. Visualization of the pelvic floor was
      reported in 93% of the procedures. In the surgeons' opinion, the RR stapler
      device was considered clinically acceptable in 93% of the procedures. In 79% of
      the procedures the surgeon preferred the RR stapler device over the stapler
      device they normally used. CONCLUSION: This study showed that the first
      experiences with the RR stapler device of 33 surgeons in 85 low rectal procedures
      are positive. It facilitates low stapling in both open and laparoscopic
      procedures. Good visibility, maneuverability and the possibility to create
      adequate distal margins were reported.

PMID- 25576760
TI  - Lipid profile changes in patients undergoing bariatric surgery: a comparative
      study between sleeve gastrectomy and mini-gastric bypass.
AB  - OBJECTIVE: To prospectively evaluate the effect of different types of bariatric
      surgery on lipid profile. METHODS: Total cholesterol (TC), High-Density
      Lipoprotein cholesterol (HDLc), Low-Density-Lipoprotein cholesterol (LDLc) and
      triglycerides (TG) levels were evaluated before surgery and at 3 different post
      operative time-points (3, 6 and 12 months) in consecutive obese subjects
      undergoing mini-gastric bypass (MGB) or sleeve gastrectomy (SG). RESULTS: At
      baseline, 74 MGB and 86 SG subjects were comparable for lipid profile and
      prevalence of hypercholesterolemia/hypertriglyceridemia. During the post
      operative follow-up, both MGB and SG subjects showed significant changes in lipid
      profile. However, at 3 months, MGB patients showed higher changes in TC (beta =
      0.179, p = 0.022) and TG (beta = 0.265, p = 0.001) than those undergoing SG. At 6
      month post-operative follow-up, these differences were confirmed only for TC.
      After a 12-month follow-up, MGB and SG were entirely comparable for changes in
      lipid profile with the exception of HDLc, whose changes were higher in SG group
      (beta = 0.130, p = 0.039). Overall, the probability to normalize lipid profile
      during the 12-month follow-up was similar in MGB and in SG patients (OR:1.24,
      95%CI:0.41-3.76, p = 0.689). CONCLUSION: Despites some differences at 3-6 post
      operative months, during a 12-month follow-up, SG and MGB showed a similar
      efficacy in the improvement of lipid profile of obese patients.

PMID- 25576761
TI  - Single-port laparoscopic reversal of Hartmann's procedure via the colostomy site.
AB  - BACKGROUND: The aim of this study was to report our initial experience with
      single-port laparoscopic reversal of Hartmann's procedure (SP-LHR). METHODS:
      Between December 2009 and March 2014, 23 patients underwent single-port
      laparoscopic reversal of Hartmann's procedure. Single-port laparoscopic surgeries
      (SPLS) were performed through the preexisting stoma site. A commercially
      available single port with one 5 mm and two 12 mm trocars was used with
      conventional straight and rigid laparoscopic instruments. Patient demographics
      and operative and postoperative outcomes were analyzed. RESULTS: SP-LHR was
      successful in 22 patients. No additional incisions for trocars or conversions to
      open surgery were necessary. In 1 patient, the procedure was aborted. The median
      operative time and postoperative length of stay were 165 min (range, 100-340 min)
      and 8 days (range, 4-31 days), respectively. The median time to the resumption of
      oral intake was 3 days (range, 1-16 days). No intraoperative complications were
      noted; there were four postoperative complications including one anastomotic
      leak. CONCLUSIONS: In our experience, SP-LHR via the colostomy site was safe and
      feasible, and may be considered an additional surgical option for experienced
      SPLS surgeons in selected patients.

PMID- 25576762
TI  - Survival impact of cytoreduction to microscopic disease for advanced stage cancer
      of the uterine corpus: a retrospective cohort study.
AB  - OBJECTIVE: To assess the impact of cytoreduction to no gross residual disease
      (R0) on overall survival (OS) in patients with stage III-IV uterine
      carcinosarcoma (CS), papillary serous/clear cell (UPSC/CC) and endometrioid
      carcinoma (EC). METHODS: We retrospectively identified 168 patients who underwent
      primary surgery for advanced uterine cancer between 1984 and 2009 in two teaching
      hospitals in Brooklyn, New York. Histology, stage, grade, residual disease (RD),
      adjuvant therapy, age, race and OS were collected. OS was calculated using the
      Kaplan-Meier method. Predictive factors were compared using the log-rank test and
      Cox regression analysis. RESULTS: Our cohort included 54 patients with CS (stage
      III, n = 32; stage IV, n = 22), 54 patients with UPSC/CC (stage III, n = 20;
      stage IV, n = 34) and 60 patients with EC (stage III, n = 45; stage IV, n = 15).
      R0 was achieved in 64% of patients with CS, in 53% of patients with UPSC/CC and
      in 68% of patients with EC. There was no interaction between histologic subtype
      and feasibility of complete cytoreduction (p = 0.39). R0 was associated with a
      median OS of 25 months (95% CI [18, 33]) versus 13 months (95% CI [8, 18]) in
      patients with gross RD (p = 0.03). This effect was uniform among histologic
      subtypes. On multivariate analysis, predictors of increased mortality were gross
      residual disease (HR = 2.0, 95% CI [1.1, 3.7], p = 0.01), stage IV (HR = 1.8, 95%
      CI [1.1, 3.1], p = 0.02) and age (HR = 1.04 per year of age, 95% CI [1.02, 1.07],
      p = 0.002). CONCLUSION: Cytoreductive surgery to R0 is associated with improved
      OS in advanced uterine cancer. This effect is uniform among histologies. There is
      no interaction between histologic subtype and feasibility of complete
      cytoreduction.

PMID- 25576763
TI  - Chewing gum and postoperative ileus in adults: a systematic literature review and
      meta-analysis.
AB  - INTRODUCTION: Post-operative ileus (POI) is a major problem following elective
      abdominal surgery. Several studies have been published investigating the use of
      chewing gum to reduce POI. These studies however, have produced variable results.
      Thus, there is currently no consensus on whether chewing gum should be widely
      instituted as a means to help reduce POI. METHODS: We performed a systematic
      literature review to evaluate whether the use of chewing gum post-operatively
      improves POI in abdominal surgery. A comprehensive review of the literature was
      conducted according to the guidelines in the PRISMA statement. The following
      databases were searched: MEDLINE, PUBMED, EMBASE, SCOPUS, Science Direct, CINAHL
      and the Cochrane Central Register of Controlled Trials. Clinical outcomes were
      extracted and meta-analysis was performed. RESULTS: There were 1019 patients from
      12 randomised controlled studies included in this review. Only one study was
      conducted in an Enhanced Recovery after Surgery (ERAS) environment. Seven of the
      twelve studies concluded that chewing gum reduced post-operative ileus. The
      remaining five studies found no clinical improvement. Overall, there was a small
      benefit in reducing time to flatus, and time to bowel motion, but no difference
      in the length of stay or complications. CONCLUSION: Chewing gum offers only a
      small benefit in reducing time to flatus and time to passage of bowel motion
      following abdominal surgery. This benefit is of limited clinical significance.
      Further studies should be conducted in a modern peri-operative care environment.

PMID- 25576764
TI  - Computational prediction of origin of replication in bacterial genomes using
      correlated entropy measure (CEM).
AB  - We have carried out an analysis on 500 bacterial genomes and found that the de
      facto GC skew method could predict the replication origin site only for 376
      genomes. We also found that the auto-correlation and cross-correlation based
      methods have a similar prediction performance. In this paper, we propose a new
      measure called correlated entropy measure (CEM) which is able to predict the
      replication origin of all these 500 bacterial genomes. The proposed measure is
      context sensitive and thus a promising tool to identify functional sites. The
      process of identifying replication origins from the output of CEM and other
      methods has been automated to analyze a large number of genomes in a faster
      manner. We have also explored the applicability of SVM based classification of
      the workability of each of these methods on all the 500 bacterial genomes based
      on its length and GC content. 

PMID- 25576765
TI  - Dendrimers complexed with HIV-1 peptides interact with liposomes and lipid
      monolayers.
AB  - AIMS: We have investigated the effect of surface charge of model lipid membranes
      on their interactions with dendriplexes formed by HIV-derived peptides and 2
      types of positively charged carbosilane dendrimers (CBD). METHODS: Interaction of
      dendriplexes with lipid membranes was measured by fluorescence anisotropy,
      dynamic light scattering and Langmuir-Blodgett techniques. The morphology of the
      complexes was examined by transmission electron microscopy. RESULTS: All
      dendriplexes independent of the type of peptide interacted with model lipid
      membranes. Negatively charged vesicles composed of a mixture of DMPC/DPPG
      interacted more strongly, and it was accompanied by an increase in anisotropy of
      the fluorescent probe localized in polar domain of lipid bilayers. There was also
      an increase in surface pressure of the lipid monolayers. Mixing negatively
      charged liposomes with dendriplexes increased liposome size and made their
      surface charges more positive. CONCLUSIONS: HIV-peptide/dendrimer complexes
      interact with model lipid membranes depending on their surface charge.
      Carbosilane dendrimers can be useful as non-viral carriers for delivering HIV
      peptides into cells.

PMID- 25576766
TI  - Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice.
AB  - Sodium meta-arsenite (SA) is an orally available arsenic compound. We
      investigated the effects of SA on the development of autoimmune type 1 diabetes.
      Female non-obese diabetic (NOD) mice were orally intubated with SA (5mg/kg/day)
      from 8weeks of age for 8weeks. The cumulative incidence of diabetes was monitored
      until 30weeks of age, islet histology was examined, and lymphocytes including T
      cells, B cells, CD4+ IFN-gamma+ cells, CD8+ IFN-gamma+ cells, CD4+ IL-4+ cells,
      and regulatory T cells were analyzed. We also investigated the diabetogenic
      ability of splenocytes using an adoptive transfer model and the effect of SA on
      the proliferation, activation, and expression of glucose transporter 1 (Glut1) in
      splenocytes treated with SA in vitro and splenocytes isolated from SA-treated
      mice. SA treatment decreased the incidence of diabetes and delayed disease onset.
      SA treatment reduced the infiltration of immunocytes in islets, and splenocytes
      from SA-treated mice showed a reduced ability to transfer diabetes. The number of
      total splenocytes and T cells and both the number and the proportion of CD4+ IFN
      gamma+ and CD8+ IFN-gamma+ T cells in the spleen were significantly reduced in SA
      treated NOD mice compared with controls. The number, but not the proportion, of
      regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either
      in vitro or in vivo inhibited proliferation of splenocytes. In addition, the
      expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment.
      These results suggest that SA reduces proliferation and activation of T cells,
      thus preventing autoimmune diabetes in NOD mice. 

PMID- 25576767
TI  - Desmoid tumors in neurosurgery: a review of the literature.
AB  - Desmoid tumors (DTs) are rare myofibroblastic neoplasms, which are mostly
      sporadic, but sometimes associated with familial adenomatous polyposis syndrome.
      Neurosurgical cases of DT have been very scarce. We review the literature
      concerning neurosurgical DTs and describe the first case of a cicatricial DT
      after the resection of vestibular schwannoma, presenting as a painful swelling in
      the retrosigmoid scar. Contrary to other localizations in the body, standard-of
      care wide margin resection cannot be performed in intracranial and spinal DTs.
      Therefore, maximally safe resection followed by radiotherapy when tumor margins
      are not free can be proposed as a treatment strategy in neurosurgical DTs. 

PMID- 25576768
TI  - Prospective associations between loneliness and emotional intelligence.
AB  - Loneliness has been linked cross-sectionally to emotional skill deficits (e.g.,
      Zysberg, 2012), but missing from the literature is a longitudinal examination of
      these relationships. The present study fills that gap by examining the
      prospective relationships between loneliness and emotional functioning in young
      adolescents in England. One hundred and ninety-six adolescents aged 11-13 years
      (90 females) took part in the study and completed the youth version of the Mayer
      Salovey-Caruso Emotional Intelligence Test (MSCEIT-YV) and the peer-related
      subscale of the Loneliness and Aloneness Scale for Children and Adolescents
      (LACA) at two time points, which were 10 months apart. Prospective associations
      were obtained for male and female adolescents separately using cross-lagged
      statistical techniques. Our results showed prospective links between
      understanding and managing emotions and loneliness for both females and males.
      Perceiving and using emotions were prospectively linked to loneliness in males
      only. Possible explanations and directions for future research are discussed. 

PMID- 25576769
TI  - The impact of men's magazines on adolescent boys' objectification and courtship
      beliefs.
AB  - Although much attention concerning the potential impact of sexualized media has
      focused on girls and women, less is known about how this content effects boys'
      perceptions of women and courtship. Accordingly, the current three-wave panel
      study investigated whether exposure to sexualizing magazines predicts adolescent
      boys' (N = 592) sexually objectifying notions of women and their beliefs about
      feminine courtship strategies. The results indicated that when boys consumed
      sexualizing magazines more often, they expressed more gender-stereotypical
      beliefs about feminine courtship strategies over time. This association was
      mediated by boys' objectification of women. The possibility of a reciprocal
      relation whereby beliefs about courtship strategies predict future consumption of
      sexualizing magazines was also explored but received no support. Discussion
      focuses on effects of sexualizing media on boys, and supports future research to
      build on multidisciplinary knowledge.

PMID- 25576770
TI  - A novel BLAST-Based Relative Distance (BBRD) method can effectively group members
      of protein arginine methyltransferases and suggest their evolutionary
      relationship.
AB  - We developed a novel BLAST-Based Relative Distance (BBRD) method by Pearson's
      correlation coefficient to avoid the problems of tedious multiple sequence
      alignment and complicated outgroup selection. We showed its application on
      reconstructing reliable phylogeny for nucleotide and protein sequences as
      exemplified by the fmr-1 gene and dihydrolipoamide dehydrogenase, respectively.
      We then used BBRD to resolve 124 protein arginine methyltransferases (PRMTs) that
      are homologues of nine mammalian PRMTs. The tree placed the uncharacterized PRMT9
      with PRMT7 in the same clade, outside of all the Type I PRMTs including PRMT1 and
      its vertebrate paralogue PRMT8, PRMT3, PRMT6, PRMT2 and PRMT4. The PRMT7/9 branch
      then connects with the type II PRMT5. Some non-vertebrates contain different
      PRMTs without high sequence homology with the mammalian PRMTs. For example, in
      the case of Drosophila arginine methyltransferase (DART) and Trypanosoma brucei
      methyltransferases (TbPRMTs) in the analyses, the BBRD program grouped them with
      specific clades and thus suggested their evolutionary relationships. The BBRD
      method thus provided a great tool to construct a reliable tree for members of
      protein families through evolution. 

PMID- 25576771
TI  - New insights into the amphibious life of Biomphalaria glabrata and susceptibility
      of its egg masses to fungal infection.
AB  - The air-breathing snail Biomphalaria glabrata proliferates in stagnant
      freshwater, and nothing is known about the survival of eggs in intermittently
      (rather than perpetually) wet habitats. In the present study their egg masses
      matured, and juveniles subsequently eclosed and were mobile in a stable water
      film of transitory habitats simulated by two different simple test devices
      described here. The viability of eggs maintained in an unstable film however, was
      diminished. The maturation of egg masses in a water film or in water was
      significantly prevented by the entomopathogenic fungi Beauveria bassiana and
      Metarhizium anisopliae. The efficiency depended on the fungal propagule and test
      environment. Hyphal bodies were more effective against egg masses than conidia.
      This appears to be a first report of activity of either entomopathogen against a
      mollusc. Both devices offer accurate and reproducible conditions to test both
      biological questions and the effects of substances or pathogens against B.
      glabrata egg masses in water films. 

PMID- 25576772
TI  - Laser-induced ocular hypertension in adult rats does not affect non-RGC neurons
      in the ganglion cell layer but results in protracted severe loss of cone
      photoreceptors.
AB  - To investigate the long-term effects of laser-photocoagulation (LP)-induced
      ocular hypertension (OHT) in the innermost and outermost (outer-nuclear and outer
      segment)-retinal layers (ORL). OHT was induced in the left eye of adult rats. To
      investigate the ganglion cell layer (GCL) wholemounts were examined at 1, 3 or 6
      months using Brn3a-immunodetection to identify retinal ganglion cells (RGCs) and
      DAPI-staining to detect all nuclei in this layer. To study the effects of LP on
      the ORL up to 6 months, retinas were: i) fresh extracted to quantify the levels
      of rod-, S- and L-opsin; ii) cut in cross-sections for morphometric analysis, or;
      iii) prepared as wholemounts to quantify and study retinal distributions of
      entire populations of RGCs (retrogradely labeled with fluorogold, FG), S- and L
      cones (immunolabeled). OHT resulted in wedge-like sectors with their apex on the
      optic disc devoid of Brn3a(+)RGCs but with large numbers of DAPI(+)nuclei. The
      levels of all opsins diminished by 2 weeks and further decreased to 20% of basal
      levels by 3 months. Cross-sections revealed focal areas of ORL degeneration. RGC
      survival at 15 days represented approximately 28% and did not change with time,
      whereas the S- and L-cone populations diminished to 65% and 80%, or to 20 and 35%
      at 1 or 6 months, respectively. In conclusion, LP induces in the GCL selective
      RGCs loss that does not progress after 1 month, and S- and L-cone loss that
      progresses for up to 6 months. Thus, OHT results in severe damage to both the
      innermost and the ORL. 

PMID- 25576773
TI  - Expressive inhibition in response to stress: implications for emotional
      processing following trauma.
AB  - Expressive inhibition--the willful restriction of expressed emotion--is
      documented in individuals reporting trauma-related distress, but its impact on
      global affective functioning remains unclear. Theoretical models propose that
      chronic activation of negative emotion and deliberate restriction of affect
      operate synergistically to produce trauma-related emotional deficits. The current
      project examined the impact of these factors on subjective experience and
      physiological activation following exposure to an analog trauma. University
      students (N=192; Mage=20, 57% female, 42% White/Non-Hispanic) viewed a graphic
      film depicting scenes of a televised suicide. Participants then viewed either a
      sadness- or humor-eliciting film under instructions to inhibit [nsadness=45,
      nhumor=52] or naturally express emotion [nsadness=48, nhumor=47]. Expressive
      inhibition was associated with restricted amusement specifically among
      participants viewing the humor film. Inhibition also produced attenuated
      sympathetic and parasympathetic recovery, irrespective of film assignment.
      Evidence of disruptions in emotional processing supports models identifying
      inhibition as a possible mechanism in post-trauma affect dysregulation.

PMID- 25576774
TI  - Mobile genetic elements in Clostridium difficile and their role in genome
      function.
AB  - Approximately 11% the Clostridium difficile genome is made up of mobile genetic
      elements which have a profound effect on the biology of the organism. This
      includes transfer of antibiotic resistance and other factors that allow the
      organism to survive challenging environments, modulation of toxin gene
      expression, transfer of the toxin genes themselves and the conversion of non
      toxigenic strains to toxin producers. Mobile genetic elements have also been
      adapted by investigators to probe the biology of the organism and the various
      ways in which these have been used are reviewed. 

PMID- 25576775
TI  - ER stress induced by the OCH1 mutation triggers changes in lipid homeostasis in
      Kluyveromyces lactis.
AB  - In Kluyveromyces lactis yeast, OCH1 encodes for the alpha-1,6-mannosyltrasferase
      that adds the initial alpha-1,6-mannose to the outer-chains of N-glycoproteins.
      Kloch1-1 mutant cells showed altered calcium homeostasis and endoplasmic
      reticulum (ER) stress. Since ER plays a major role in lipid biosynthesis and
      lipid droplet (LD) formation, herein the impact of Och1p depletion on lipid
      homeostasis was investigated. Transcriptional profiles of genes involved in
      biosynthesis of fatty acids, their amount and composition changed in mutant
      cells. An increased amount of ergosterol was determined in these cells. Enhanced
      transcription of genes involved in both synthesis and mobilization of LDs was
      also found in Kloch1-1 cells, accompanied by a reduced amount of LDs. We provide
      evidence that ER alterations, determined by protein misfolding as a result of
      reduced N-glycosylation, induced altered lipid homeostasis in Kloch1-1 cells.
      Chemical chaperone 4-phenyl butyrate (4-PBA) slightly alleviated the LD phenotype
      in cells depleted of Och1p. Remarkably, complete suppression of ER stress, via
      increased expression of plasma membrane calcium channel subunit Mid1, fully
      restored lipid homeostasis in mutant cells. To further reinforce this finding,
      low numbers of LDs were observed in wild type cells when ER stress was triggered
      by DTT treatment. 

PMID- 25576776
TI  - The potential of clostridial spores as therapeutic delivery vehicles in tumour
      therapy.
AB  - Despite substantial investment in prevention, treatment and aftercare, cancer
      remains a leading cause of death worldwide. More effective and accessible
      therapies are required. A potential solution is the use of endospore forming
      Clostridium species, either on their own, or as a tumour delivery vehicle for
      anti-cancer drugs. This is because intravenously injected spores of these
      obligate anaerobes can exclusively germinate in the hypoxic/necrotic regions
      present in solid tumours and nowhere else in the body. Research aimed at
      exploiting this unique phenomenon in anti-tumour strategies has been ongoing
      since the early part of the 20th century. Only in the last decade, however, has
      there been significant progress in the development and refinement of strategies
      based on spore-mediated tumour colonisation using a range of clostridial species.
      Much of this progress has been due to advances in genomics and our ability to
      modify strains using more sophisticated gene tools. 

PMID- 25576777
TI  - Anterograde conduction to the His bundle during right ventricular overdrive
      pacing distinguishes septal pathway atrioventricular reentry from atypical
      atrioventricular nodal reentrant tachycardia.
AB  - BACKGROUND: Distinguishing orthodromic atrioventricular reciprocating tachycardia
      (ORT) using a retrograde septal accessory pathway (AP) from atypical
      atrioventricular nodal reentrant tachycardia (AVNRT) may be challenging.
      Specifically, excluding the presence and participation of an AP may require
      multiple diagnostic maneuvers. OBJECTIVE: The purpose of this study was to assess
      the relative value of commonly used right ventricular (RV) pacing maneuvers,
      including identification of anterograde His-bundle activation with entrainment,
      to differentiate ORT using a retrograde septal AP from atypical AVNRT. METHODS:
      From March 2009 to June 2014, 56 patients (28 female; age 43.9 +/- 17.4 years)
      who underwent electrophysiologic study and ablation for supraventricular
      tachycardia (26 ORT using septal AP and 30 atypical AVNRT) that exhibited a
      concentric atrial activation pattern and a septal ventriculoatrial interval >70
      ms were analyzed. RESULTS: Overdrive pacing maneuvers or ventricular extrastimuli
      failed on at least 1 occasion to correctly identify a septal AP. Overall, 16 ORT
      patients and 26 AVNRT patients had successful RV entrainment, and 12 (75%) ORT
      patients showed anterograde His capture (11 patients) and/or anterograde septal
      ventricular capture (3 patients). None of the patients with atypical AVNRT showed
      anterograde conduction to the His bundle with entrainment. CONCLUSION: RV pacing
      maneuvers are useful to exclude an AP in patients with AVNRT having concentric
      atrial activation sequence and a septal ventriculoatrial interval >70 ms;
      however, none are consistently diagnostic. When observed in this patient
      population, anterograde His-bundle or septal ventricular capture during RV
      entrainment was diagnostic for ORT using a septal AP.

PMID- 25576778
TI  - To the Editor--Interatrial block: Another risk to take into account after
      radiofrequency ablation of typical atrial flutter.

PMID- 25576780
TI  - Automated external defibrillator rescues among children with diagnosed and
      treated long QT syndrome.
AB  - BACKGROUND: Long QT syndrome (LQTS) is a potentially lethal yet highly treatable
      cardiac channelopathy. A comprehensive LQTS-directed treatment program often
      includes an automated external defibrillator (AED). OBJECTIVE: The purpose of
      this study was to determine the incidence of AED rescues among children
      evaluated, risk-stratified, and treated in an LQTS specialty center. METHODS: We
      performed a retrospective review of the electronic medical records to identify
      1665 patients evaluated in our Genetic Heart Rhythm Clinic (1999-2013). Subset
      analysis was performed on 291 children managed without an implantable
      cardioverter-defibrillator (ICD). RESULTS: The average age at diagnosis was 8.3
      +/- 5.7 years with an average. QTc of 463 +/- 40 ms (17% >=500 ms). The
      represented LQTS genotypes included type 1 (LQT1) in 52%, type 2 (LQT2) in 35%,
      and type 3 (LQT3) in 7%. During follow-up, 3 of 291 children (1%) had a cardiac
      arrest with an appropriate AED rescue (2/51 symptomatic, 1/240 asymptomatic). The
      first AED rescue occurred during exercise in a symptomatic 3-year-old boy with
      compound LQT1 treated with beta-blocker and videoscopic left cardiac sympathetic
      denervation (LCSD). The second AED rescue occurred in a remotely symptomatic 14
      year-old boy with high-risk LQT2 (QTc >550 ms) on a beta-blocker who previously
      declined a prophylactic ICD. The third AED rescue involved an asymptomatic 17
      year-old girl with LQT3 on mexiletine who collapsed in school. CONCLUSION: An AED
      should seldom be necessary in an appropriately treated child with LQTS.
      Nevertheless, despite only 3 AED rescues in more than 1700 patient-years, an AED
      can be a lifesaving and cost-effective part of an LQTS patient's comprehensive
      sudden death prevention program.

PMID- 25576779
TI  - Sinus rhythm restoration and arrhythmia noninducibility are major predictors of
      arrhythmia-free outcome after ablation for long-standing persistent atrial
      fibrillation: a prospective study.
AB  - BACKGROUND: The impact of restoring sinus rhythm (SR) by initial ablation in
      patients with long-standing persistent atrial fibrillation (LSPAF) is not fully
      established. OBJECTIVE: The purpose of this study was to investigate the
      prognostic value of SR restoration at the initial procedure and arrhythmia
      noninducibility at the final repeat procedure for long-term outcome. METHODS: A
      total of 203 patients (22% female; age 59 +/- 9 years) underwent stepwise
      catheter ablation for LSPAF. RESULTS: The procedural end-point of SR restoration
      was achieved in 50% of patients. During follow-up (median 48 months) and after
      1.7 procedures per patient, 72% of patients were free from arrhythmia off
      antiarrhythmic drugs. Failure to restore SR was independently predicted by left
      atrial (LA) long-axis diameter >=68 mm (relative risk [RR] 1.55, P = .03],
      proportion of high-voltage LA sites <20% (RR 1.62, P = .02), and left atrial
      appendage (LAA) atrial fibrillation cycle length (AFCL) <155 ms (RR 1.5, P =
      .05). Arrhythmia recurrence after the initial procedure was predicted by SR
      nonrestoration (RR 2.99, P <.000001) and LAA AFCL >=155 ms (RR 1.90, P = .0002).
      Arrhythmia recurrence after the final procedure was predicted by SR
      nonrestoration at the initial procedure (RR 2.83, P = .0007), persistent AF
      duration >=24 months (RR 2.74, P = .002), LAA outflow velocity <40 cm/s (RR 2.21,
      P = .006), and LAA AFCL >=155 ms (RR 1.92, P = .02). In 115 patients with repeat
      procedure(s), failure to achieve arrhythmia noninducibility at the final
      procedure (19% of patients) was associated with arrhythmia recurrence (RR 8.9, P
      < .000001). CONCLUSION: SR restoration at the initial procedure and arrhythmia
      noninducibility at the last repeat procedure were major predictors of arrhythmia
      free outcome after ablation for LSPAF.

PMID- 25576781
TI  - Arsenic speciation in the dispersible colloidal fraction of soils from a mine
      impacted creek.
AB  - Arsenic and iron speciation in the dispersible colloid fraction (DCF; 10-1000 nm)
      from an As-rich mine waste pile, sediments of a streambed that collects runoff
      from waste pile, the streambed subsoil, and the sediments of a downstream pond
      were investigated by combining asymmetrical-flow field-flow fractionation
      (AsFlFFF)/inductively-coupled plasma-mass spectrometry (ICP-MS), transmission
      electron microscopy (TEM) and X-ray absorption (XAS) spectroscopy. Calcium, Fe
      and As (Fe/As molar ratio ~ 1) were the main components of the DCF from waste
      pile. TEM/EDS and As and Fe XAS analysis revealed the presence of nanoparticle
      scorodite in this same DCF, as well as Fe nanoparticles in all samples downstream
      of the waste pile. Arsenic and Fe XAS showed As(V) adsorbed onto nanoparticulate
      ferrihydrite in the DCF of downstream samples. Micro-X-ray fluorescence indicated
      a strong correlation between Fe and As in phyllosilicate/Fe(3+) (oxi) hydroxide
      aggregates from the sediment pond. Fractionation analysis showed the mean
      particle size of the DCF from the streambed sample to be smaller than that of the
      streambed subsoil and sediment ponds samples. These results show that an
      important and variable fraction of As may be bound to dispersible colloids that
      can be released from contaminated soils and transported downstream in natural
      systems.

PMID- 25576782
TI  - Enhancement of soil retention for phenanthrene in binary cationic gemini and
      nonionic surfactant mixtures: characterizing two-step adsorption and partition
      processes through experimental and modeling approaches.
AB  - The enhancement of soil retention for phenanthrene (PHE) through the addition of
      a binary mixture of cationic gemini (12-2-12) and nonionic surfactants (C12E10)
      was investigated. The maximum apparent sorption coefficient Kd(*) reached 4247.8
      mL/g through the addition of mixed 12-2-12 gemini and C12E10 surfactants, which
      was markedly higher than the summed individual results in the presence of
      individual 12-2-12 gemini (1148.6 mL/g) or C12E10 (210.0 mL/g) surfactant.
      However, the sorption of 12-2-12 gemini was inhibited by the increasing C12E10
      dose; and a higher initial 12-2-12 gemini dose showed a higher "desorption" rate.
      The present study also addressed the sorption behavior of the single 12-2-12
      gemini surfactant at the soil/aqueous interface. The sorption isotherm was
      divided into two steps to elucidate the sorption process; and the sorption
      schematics were proposed to elaborate the growth of surfactant aggregates
      corresponding to the various steps of the sorption isotherm. Finally, a two-step
      adsorption and partition model (TAPM) was developed to simulate the sorption
      process. Analysis of the equilibrium data indicated that the sorption isotherms
      of 12-2-12 gemini fitted the TAPM model better. Thermodynamic calculations
      confirmed that the 12-2-12 gemini sorption at the soil/aqueous interface was
      spontaneous and exothermic from 288 to 308K.

PMID- 25576783
TI  - Kinetic, equilibrium and thermodynamic studies on sorption of uranium and thorium
      from aqueous solutions by a selective impregnated resin containing carminic acid.
AB  - In this work, the removal of uranium and thorium ions from aqueous solutions was
      studied by solid-liquid extraction using an advantageous extractant-impregnated
      resin (EIR) prepared by loading carminic acid (CA) onto Amberlite XAD-16 resin
      beads. Batch sorption experiments using CA/XAD-16 beads for the removal of U(VI)
      and Th(IV) ions were carried out as a function of several parameters, like
      equilibration time, metal ion concentration, etc. The equilibrium data obtained
      from the sorption experiments were adjusted to the Langmuir isotherm model and
      the calculated maximum sorption capacities in terms of monolayer sorption were in
      agreement with those obtained from the experiments. The experimental data on the
      sorption behavior of both metal ions onto the EIR beads fitted well in both
      Bangham and intra-particle diffusion kinetic models, indicating that the intra
      particle diffusion is the rate-controlling step. The thermodynamic studies at
      different temperatures revealed the feasibility and the spontaneous nature of the
      sorption process for both uranium and thorium ions. 

PMID- 25576784
TI  - Why do we need a nonhuman primate model of smoking-induced COPD?
AB  - This Commentary highlights the article by Polverino et al, describing the
      development of a novel nonhuman primate model of cigarette smoke-induced chronic
      obstructive pulmonary disease. 

PMID- 25576785
TI  - Identification of long-range epigenetic silencing on chromosome 15q25 and its
      clinical implication in gastric cancer.
AB  - Recent genome-wide epigenomic and transcription profiling studies have
      demonstrated that epigenetic silencing can encompass multiple neighboring genes,
      termed as long-range epigenetic silencing (LRES). Herein, we identified a novel
      LRES region by comparing gene expression of human colon cancer HCT116 cells with
      their DNA methyltransferase 1 and DNA methyltransferase 3B double-knockout
      derivative double-knockout cells. Ten consecutive genes spanning 3 Mb of
      chromosome 15q25 were coordinately silenced, with eight genes showing promoter
      CpG island hypermethylation and enrichment of repressive histone marks, which
      were evaluated by bisulfite sequencing analysis and chromatin immunoprecipitation
      assay. Comparison of primary gastric tumor specimens with normal tissue confirmed
      that the long-range silencing of this region was tumor specific. Methylation of
      genes within the LRES region was evaluated in 190 gastric tumor tissues using the
      MethyLight assay, and their association with clinicopathological features, such
      as older age, high-grade differentiation, and diffuse or mixed-type histology,
      was determined. LRES-positive gastric cancer patients (six or more methylated
      genes) showed lower recurrence and better survival. Our findings emphasize the
      differential dynamics of DNA methylation and histone modification, indicating the
      importance of studying the relationship of each epigenetic modification in the
      context of chromatin domains. Patients with LRES showed lower recurrence and
      better prognosis, indicating that stratifying patients according to underlying
      molecular features, such as LRES regions, may better predict recurrence and
      survival. 

PMID- 25576786
TI  - Corticosteroid-loaded biodegradable nanoparticles for prevention of corneal
      allograft rejection in rats.
AB  - Immunologic graft rejection is one of the main causes of short and long-term
      graft failure in corneal transplantation. Steroids are the most commonly used
      immunosuppressive agents for postoperative management and prevention of corneal
      graft rejection. However, steroids delivered in eye drops are rapidly cleared
      from the surface of the eye, so the required frequency of dosing for corneal
      graft rejection management can be as high as once every 2h. Additionally, these
      eye drops are often prescribed for daily use for 1 year or longer, which can
      result in poor patient compliance and steroid-related side effects. Here, we
      report a biodegradable nanoparticle system composed of Generally Regarded as Safe
      (GRAS) materials that can provide sustained release of corticosteroids to prevent
      corneal graft rejection following subconjunctival injection provided initially
      during transplant surgery. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles
      containing dexamethasone sodium phosphate (DSP) exhibited a size of 200 nm, 8
      wt.% drug loading, and sustained drug release over 15 days in vitro under sink
      conditions. DSP-loaded nanoparticles provided sustained ocular drug levels for at
      least 7 days after subconjunctival administration in rats, and prevented corneal
      allograft rejection over the entire 9-week study when administered weekly. In
      contrast, control treatment groups that received weekly injections of either
      placebo nanoparticles, saline, or DSP in solution demonstrated corneal graft
      rejection accompanied by severe corneal edema, neovascularization and opacity
      that occurred in <= 4 weeks. Local controlled release of corticosteroids may
      reduce the rate of corneal graft rejection, perhaps especially in the days
      immediately following surgery when risk of rejection is highest and when typical
      steroid eye drop administration requirements are particularly onerous.

PMID- 25576787
TI  - Nanogrooved surface-patterns induce cellular organization and axonal outgrowth in
      neuron-like PC12-cells.
AB  - Modulation of a materials surface topography can be used to steer various aspects
      of adherent cell behaviour, such as cell directional organization. Especially
      nanometric sized topographies, featuring sizes similar to for instance the axons
      of the spiral ganglion cells, are interesting for such purpose. Here, we utilized
      nanosized grooves in the range of 75-500 nm, depth of 30-150 nm, and pitches
      between 150 nm and 1000 nm for cell culture of neuron-like PC12 cells. The
      organizational behaviour was evaluated after 7 days of culture by bright field
      and scanning electron microscopy. Nanotopographies were shown to induce aligned
      cell-body/axon orientation and an increased axonal outgrowth. Our findings
      suggest that a threshold for cell body alignment of neuronal cells exists on
      grooved topographies with a groove width of 130 nm, depth of 70 nm and pitch of
      300 nm, while axon alignment can already be induced by grooves with 135 nm width,
      52 nm depth and 200 nm pitch. However, no threshold has been found for axonal
      outgrowth, as all of the used patterns increased outgrowth of PC12-axons. In
      conclusion, surface nanopatterns have the potential to be utilized as an
      electrode modification for a stronger separation of cells, and can be used to
      direct cells towards the electrode contacts of cochlear implants. 

PMID- 25576788
TI  - Morphological and morphometric characterization of direct transdifferentiation of
      support cells into hair cells in ototoxin-exposed neonatal utricular explants.
AB  - We have studied aminoglycoside-induced vestibular hair-cell renewal using long
      term culture of utricular macula explants from 4-day-old rats. Explanted utricles
      were exposed to 1 mM of gentamicin for 48 h, during 2nd and 3rd days in vitro
      (DIV), and then recovering in unsupplemented medium. Utricles were harvested at
      specified time points from the 2nd through the 28th DIV. The cellular events that
      occurred within hair cell epithelia during the culture period were documented
      from serial sectioned specimens. Vestibular hair cells (HCs) and supporting cells
      (SCs) were systematically counted using light microscopy (LM) with the assistance
      of morphometric software. Ultrastructural observations were made from selected
      specimens with transmission electron microscopy (TEM). After 7 DIV, i.e. four
      days after gentamicin exposure, the density of HCs was 11% of the number of HCs
      observed in non-gentamicin-exposed control explants. At 28 DIV the HC density was
      61% of the number of HCs observed in the control group explant specimens.
      Simultaneously with this increase in HCs there was a corresponding decline in the
      number of SCs within the epithelium. The proportion of HCs in relation to SCs
      increased significantly in the gentamicin-exposed explant group during the 5th to
      the 28th DIV period of culture. There were no significant differences in the
      volume estimations of the gentamicin-exposed and the control group explants
      during the observed period of culture. Morphological observations showed that
      gentamicin exposure induced extensive loss of HCs within the epithelial layer,
      which retained their intact apical and basal linings. At 7 to 14 DIV (i.e. 3-11
      days after gentamicin exposure) a pseudostratified epithelium with multiple
      layers of disorganized cells was observed. At 21 DIV new HCs were observed that
      also possessed features resembling SCs. After 28 DIV a new luminal layer of HCs
      with several layers of SCs located more basally characterized the gentamicin
      exposed epithelium. No mitoses were observed within the epithelial layer of any
      explants. Our conclusion is that direct transdifferentiation of SCs into HCs was
      the only process contributing to the renewal of HCs after gentamicin exposure in
      these explants of vestibular inner ear epithelia obtained from the labyrinths of
      4-day-old rats.

PMID- 25576789
TI  - Informative prior distributions for ELISA analyses.
AB  - Immunoassays are capable of measuring very small concentrations of substances in
      solutions and have an immense range of application. Enzyme-linked immunosorbent
      assay (ELISA) tests in particular can detect the presence of an infection, of
      drugs, or hormones (as in the home pregnancy test). Inference of an unknown
      concentration via ELISA usually involves a non-linear heteroscedastic regression
      and subsequent prediction, which can be carried out in a Bayesian framework. For
      such a Bayesian inference, we are developing informative prior distributions
      based on extensive historical ELISA tests as well as theoretical considerations.
      One consideration regards the quality of the immunoassay leading to two practical
      requirements for the applicability of the priors. Simulations show that the
      additional prior information can lead to inferences which are robust to
      reasonable perturbations of the model and changes in the design of the data. On
      real data, the applicability is demonstrated across different laboratories, for
      different analytes and laboratory equipment as well as for previous and current
      ELISAs with sigmoid regression function. Consistency checks on real data (similar
      to cross-validation) underpin the adequacy of the suggested priors. Altogether,
      the new priors may improve concentration estimation for ELISAs that fulfill
      certain design conditions, by extending the range of the analyses, decreasing the
      uncertainty, or giving more robust estimates. Future use of these priors is
      straightforward because explicit, closed-form expressions are provided. This work
      encourages development and application of informative, yet general, prior
      distributions for other types of immunoassays. 

PMID- 25576790
TI  - Nuclear factor kappa B-dependent Zif268 expression in hippocampus is required for
      recognition memory in mice.
AB  - Long-term memory formation requires gene expression after acquisition of new
      information. The first step in the regulation of gene expression is the
      participation of transcription factors (TFs) such as nuclear factor kappa B (NF
      kB), which are present before the neuronal activity induced by training. It was
      proposed that the activation of these types of TFs allows a second step in gene
      regulation by induction of immediate-early genes (IEGs) whose protein products
      are, in turn, TFs. Between these IEGs, zif268 has been found to play a critical
      role in long-term memory formation and reprocessing after retrieval. Here we
      found in mice hippocampus that, on one hand, NF-kB was activated 45 min after
      training in a novel object recognition (NOR) task and that inhibiting NF-kB
      immediately after training by intrahippocampal administration of NF-kB Decoy DNA
      impaired NOR memory consolidation. On the other hand, Zif268 protein expression
      was induced 45 min after NOR training and the administration of DNA antisense to
      its mRNA post-training impaired recognition memory. Finally, we found that the
      inhibition of NF-kB by NF-kB Decoy DNA reduced significantly the training-induced
      Zif268 increment, indicating that NF-kB is involved in the regulation of Zif268
      expression. Thus, the present results support the involvement of NF-kB activity
      dependent Zif268 expression in the hippocampus during recognition memory
      consolidation.

PMID- 25576791
TI  - Co-morbid beta-amyloid toxicity and stroke produce impairments in an ambiguous
      context task in rats without any impairment in spatial working memory.
AB  - Sporadic Alzheimer's disease (AD) accounts for a high proportion of AD cases.
      Therefore, it is of importance to investigate other factors that contribute to
      the etiology and progression of AD. AD is characterized by decreased cholinergic
      tone, tau hyperphosphorylation and beta-amyloid (Abeta) accumulation. In addition
      to the hallmark pathology, other factors have been identified that increase the
      risk of AD, including stroke. This study examined the combined effects of beta
      amyloid administration and unilateral stroke in an animal model of AD. Adult rats
      were given a sham surgery, bilateral intraventricular infusion of 10 MUL of 50n
      mol Abeta(25-35), a unilateral injection of endothelin-1 into the right striatum,
      or Abeta and endothelin-1 administration in combination. Following a recovery
      period, rats were tested in the 1-trial place learning variant of the Morris
      water task followed by an ambiguous discriminative fear-conditioning to context
      task. After behavioural assessment, rats were euthanized, and representative
      sections of the medial septum were analyzed for differences in choline
      acetyltransferase (ChAT) immunohistochemistry. No differences were observed in
      spatial working memory, but the combined effect of Abeta and stroke resulted in
      deficits in the discriminative fear-conditioning to context task. A trend towards
      decreased ChAT-positive staining in the medial septum was observed. This study
      indicates that Abeta and stroke in combination produce worse functional
      consequences than when experienced alone, furthering the concept of AD as a
      disease with multiple and complex etiologies.

PMID- 25576792
TI  - Total- and methyl-mercury concentrations and methylation rates across the
      freshwater to hypersaline continuum of the Great Salt Lake, Utah, USA.
AB  - We examined mercury (Hg) speciation in water and sediment of the Great Salt Lake
      and surrounding wetlands, a locale spanning fresh to hypersaline and oxic to
      anoxic conditions, in order to test the hypothesis that spatial and temporal
      variations in Hg concentration and methylation rates correspond to observed
      spatial and temporal trends in Hg burdens previously reported in biota. Water
      column, sediment, and pore water concentrations of methylmercury (MeHg) and total
      mercury (THg), as well as related aquatic chemical parameters were examined.
      Inorganic Hg(II)-methylation rates were determined in selected water column and
      sediment subsamples spiked with inorganic divalent mercury (204Hg(II)). Net
      production of Me204Hg was expressed as apparent first-order rate constants for
      methylation (kmeth), which were also expanded to MeHg production potential (MPP)
      rates via combination with tin reducible 'reactive' Hg(II) (Hg(II)R) as a proxy
      for bioavailable Hg(II). Notable findings include: 1) elevated Hg concentrations
      previously reported in birds and brine flies were spatially proximal to the
      measured highest MeHg concentrations, the latter occurring in the anoxic deep
      brine layer (DBL) of the Great Salt Lake; 2) timing of reduced Hg(II)-methylation
      rates in the DBL (according to both kmeth and MPP) coincides with reduced Hg
      burdens among aquatic invertebrates (brine shrimp and brine flies) that act as
      potential vectors of Hg propagation to the terrestrial ecosystem; 3) values of
      kmeth were found to fall within the range reported by other studies; and 4) MPP
      rates were on the lower end of the range reported in methodologically comparable
      studies, suggesting the possibility that elevated MeHg in the anoxic deep brine
      layer results from its accumulation and persistence in this quasi-isolated
      environment, due to the absence of light (restricting abiotic photo
      demethylation) and/or minimal microbiological demethylation.

PMID- 25576793
TI  - Evaluating the effectiveness of on-street bicycle lane and assessing risk to
      bicyclists in Charlotte, North Carolina.
AB  - The objectives of this manuscript are (1) to evaluate the effectiveness of on
      street bicycle lane in reducing crashes involving bicyclists on urban roads, (2)
      to quantify and compare risk to bicyclists on road segments with and without on
      street bicycle lane, (3) to evaluate the effect of on-street bicycle lane on
      other road network users (all crashes), and, (4) to assess the role of on-network
      characteristics (speed limit, the number of lanes, the width of on-street bicycle
      lane, the width of the right-most travel lane, and, the numbers of driveways,
      unsignalized approaches and signalized intersections per unit distance) on risk
      to bicyclists. Data for thirty-six segments with on-street bicycle lane and
      twenty-six segments without on-street bicycle lane in the city of Charlotte,
      North Carolina were extracted to compute and compare measures such as the number
      of bicycle crashes per center-lane mile, the number of bicycle crashes per annual
      million vehicle miles traveled (MVMT), the number of all crashes per center-lane
      mile, and the number of all crashes per MVMT. The results obtained from analysis
      indicate that bicyclists are three to four times at higher risk (based on traffic
      conditions) on segments without on-street bicycle lane than when compared to
      segments with on-street bicycle lane. An analysis conducted considering all
      crashes showed that on-street bicycle lanes do not have a statistically
      significant negative effect on overall safety. An increase in annual MVMT
      (exposure) and the number of signalized intersections per mile increases the
      number of bicycle crashes, while an increase in on-street bicycle lane width or
      right-most travel lane width (if on-street bicycle lane cannot be provided)
      decreases the number of bicycle crashes. Installing wider on-street bicycle
      lanes, limiting driveways to less than 50 per mile and unsignalized approaches to
      less than 10 per mile, increasing spacing between signalized intersections, and,
      facilitating wider right-most travel lane if on-street bicycle lane cannot be
      provided reduces occurrence of bicycle crashes and lowers risk to bicyclists on
      roads. 

PMID- 25576794
TI  - Structure of inorganic pyrophosphatase from Staphylococcus aureus reveals
      conformational flexibility of the active site.
AB  - Cytoplasmic inorganic pyrophosphatase (PPiase) is an enzyme essential for
      survival of organisms, from bacteria to human. PPiases are divided into two
      structurally distinct families: family I PPiases are Mg(2+)-dependent and present
      in most archaea, eukaryotes and prokaryotes, whereas the relatively less
      understood family II PPiases are Mn(2+)-dependent and present only in some
      archaea, bacteria and primitive eukaryotes. Staphylococcus aureus (SA), a
      dangerous pathogen and a frequent cause of hospital infections, contains a family
      II PPiase (PpaC), which is an attractive potential target for development of
      novel antibacterial agents. We determined a crystal structure of SA PpaC in
      complex with catalytic Mn(2+) at 2.1A resolution. The active site contains two
      catalytic Mn(2+) binding sites, each half-occupied, reconciling the previously
      observed 1:1 Mn(2+):enzyme stoichiometry with the presence of two divalent metal
      ion sites in the apo-enzyme. Unexpectedly, despite the absence of the substrate
      or products in the active site, the two domains of SA PpaC form a closed active
      site, a conformation observed in structures of other family II PPiases only in
      complex with substrate or product mimics. A region spanning residues 295-298,
      which contains a conserved substrate binding RKK motif, is flipped out of the
      active site, an unprecedented conformation for a PPiase. Because the mutant of
      Arg295 to an alanine is devoid of activity, this loop likely undergoes an induced
      fit conformational change upon substrate binding and product dissociation. This
      closed conformation of SA PPiase may serve as an attractive target for rational
      design of inhibitors of this enzyme. 

PMID- 25576795
TI  - Real-time UV imaging identifies the role of pH in insulin dissolution behavior in
      hydrogel-based subcutaneous tissue surrogate.
AB  - For parenteral biopharmaceuticals, subcutaneous diffusion and, in the case of
      solid implants or suspensions, dissolution may govern the clinical profile of the
      drug product. Insight into the dissolution and diffusion processes of
      biopharmaceuticals after parenteral administration is fundamental in the
      development of new protein drug formulations. Using insulin as a model compound,
      the aim of this work was to develop a UV imaging-based method to study the real
      time dissolution and diffusion behavior of solid protein drugs under stagnant
      conditions in a hydrogel matrix mimicking the subcutaneous tissue. Dissolution of
      proteins and peptides is a complex phenomenon as it may be coupled to the
      complicated acid base properties of these substances. UV imaging allowed the real
      time dissolution and diffusion processes of insulin at different pH values and of
      different insulins to be studied. Dissolution rates were obtained, and the
      quantitative performance of the developed UV imaging method was verified. It was
      shown that the UV imaging dissolution method was able to differentiate between
      the behavior of different insulins and that human insulin dissolution was highly
      dependent on pH. pH effects in the microenvironment of the human insulin compacts
      at pH 7.40 and 3.00 were observed by UV-Vis imaging, explaining the different
      dissolution kinetics of human insulin at pH 7.40 and 3.00 as compared to pH 5.40.
      In conclusion, UV-Vis imaging may be a useful tool for studying dissolution,
      diffusion and pH effects in the vicinity of solid protein drug in a hydrogel
      matrix with the aim of achieving a better understanding of in vivo dissolution
      processes. 

PMID- 25576796
TI  - Addressing the recovery of feeding rates in post-exposure feeding bioassays:
      Cyathura carinata as a case study.
AB  - Post-exposure bioassays are used in environmental assessment as a cost-effective
      tool, but the effects of organism's recovery after exposure to pollutant has not
      yet been addressed in detail. The recoveries of post-exposure feeding rates after
      being exposed to two sublethal concentrations of cadmium during two different
      exposure periods (48h and 96h) were evaluated under laboratory conditions using
      the estuarine isopod Cyathura carinata. Results showed that feeding depression
      was a stable endpoint up to 24h after cadmium exposure, which is useful for
      ecotoxicological bioassays. 

PMID- 25576797
TI  - Injury-specific promoters enhance herpes simplex virus-mediated gene therapy for
      treating neuropathic pain in rodents.
AB  - Chronic neuropathic pain is often difficult to treat with current pain
      medications. Gene therapy is presently being explored as a therapeutic approach
      for the treatment of neuropathic and cancer pain. In this study, we sought to use
      an injury-specific promoter to deliver the mu-opioid receptor (MOR) transgene
      such that expression would occur during the injured state only in response to
      release of injury-specific galanin. To determine whether an injury-specific
      promoter can produce neuron-specific MOR expression and enhanced antinociception,
      we compared animals infected with a galanin promoter virus (galMOR) or a human
      cytomegalovirus promoter virus (cmvMOR). In behavioral assays, we found an
      earlier onset and a larger magnitude of antinociception in animals infected with
      galMOR compared with cmvMOR. Immunohistochemical analysis of dorsal root ganglion
      neurons revealed a significant increase in MOR-positive staining in cmvMOR- and
      galMOR-treated mice. Spinal cord sections from galMOR-treated mice showed a
      greater increase in density but not area of MOR-positive staining. These results
      suggest that using injury-specific promoters to drive gene expression in primary
      afferent neurons can influence the onset and magnitude of antinociception in a
      rodent model of neuropathic pain and can be used to upregulate MOR expression in
      populations of neurons that are potentially injury specific. PERSPECTIVE: An
      injury-specific promoter (galMOR) was used to drive MOR expression in a
      population- and injury-specific manner. GalMOR increased antinociception and
      density of MOR staining in the spinal cord. This article presents evidence that
      promoter selection is an important component in successful gene expression in an
      injury- and population-specific manner.

PMID- 25576798
TI  - Neuronal activity patterns in the mediodorsal thalamus and related cognitive
      circuits are modulated by metabotropic glutamate receptors.
AB  - The mediodorsal thalamus (MD) likely plays an important role in cognition as it
      receives abundant afferent connections from the amygdala and prefrontal cortex
      (PFC). Indeed, disturbed activity within the MD is thought to precipitate
      cognitive deficits associated with schizophrenia. As compounds acting at the
      Group II metabotropic glutamate (mGlu) receptors (subtypes mGlu2/mGlu3) have
      efficacy in animal models of schizophrenia, we investigated whether a Group II
      agonist and an mGlu2 positive allosteric modulator (PAM) could modulate MD
      activity. Extracellular single-unit recordings were made in vivo from MD neurones
      in anaesthetised rats. Responses were elicited by electrical stimulation of the
      PFC and/or amygdala, with Group II compounds locally applied as required. The
      Group II agonist reduced inhibition evoked in the MD: an effect manifested as an
      increase in short-latency responses, and a decrease in long-latency burst-firing.
      This disinhibitory action of the Group II receptors in the MD represents a
      mechanism of potential therapeutic importance as increased inhibition in the MD
      has been associated with cognitive deficit-onset. Furthermore, as co-application
      of the mGlu2 PAM did not potentiate the Group II agonist effects in the MD, we
      suggest that the Group II disinhibitory effect is majority-mediated via mGlu3.
      This heterogeneity in Group II receptor thalamic physiology bears consequence, as
      compounds active exclusively at the mGlu2 subtype are unlikely to perturb
      maladapted MD firing patterns associated with cognitive deficits, with activity
      at mGlu3 receptors possibly more appropriate. Indeed, polymorphisms in the mGlu3,
      but not the mGlu2, gene have been detected in patients with schizophrenia. 

PMID- 25576799
TI  - Diagnosis of a novel hemoglobinopathy of compound heterozygosity of hemoglobin
      S/hemoglobin Q India.
AB  - BACKGROUND: A novel double heterozygosity for the alpha chain variant Hb Q India
      and beta chain variant Hb S is described. Hb S is prevalent in the central part
      of India while Hb Q India in its heterozygous state is found mainly in Sindhi
      families. METHODS: Identification of both the variants, Hb S and Hb Q India, was
      done based on chromatograms of HPLC and capillary zone electrophoresis (CE).
      Confirmation of variants was done by PCR based amplification refractory mutation
      system (ARMS) technique. RESULTS: Both HPLC and CE confirmed the presence of Hb
      S. HPLC showed a pointed narrow peak of Hb Q India at retention time of 4.55min
      while it is eluted in Hb D zone on CE. A hybrid variant of these alpha and beta
      globin chains was eluted in Hb C window and Hb C zone on HPLC and CE
      respectively. Molecular studies using ARMS technique confirmed these findings.
      Both the cases showed positive sickling test and presented with mild anemia.
      CONCLUSION: This is a unique 2 index cases for compound heterozygosity of Hb S
      with Hb Q India.

PMID- 25576801
TI  - Evolutionary aspects in intermediate filament proteins.
AB  - Intermediate filament (IF) proteins, together with tubulins and actins,
      constitute the majority of cytoskeletal proteins in metazoans. Proteins of the IF
      family fulfil increasingly diverse functions but share common structural
      features. Phylogenetic analysis within the metazoan lineage traces back their
      origin to a common lamin-like ancestor. Major steps in lamin evolution occurred
      at the base of the vertebrate radiation, while cytoplasmic IF protein subfamilies
      evolved independently in the major metazoan lineages. 

PMID- 25576800
TI  - Increased expression of IL-18 in the serum and islets of type 1 diabetics.
AB  - Type 1 diabetes (T1D) is a chronic disease characterized by autoimmune-mediated
      destruction of pancreatic insulin-producing beta cells. Interleukin (IL)-18 is a
      pro-inflammatory cytokine implicated in the pathogenesis of a number of
      inflammatory diseases. Here, we analyzed IL-18 levels in the plasma of juveniles
      with T1D. Compared to control subjects, IL-18 levels were significantly elevated
      in patients with T1D. On the other hand, levels of IL-18 binding protein (IL
      18BP) and IL-37, two negative regulators of IL-18 function, remained unchanged
      when comparing T1D to control samples. Notably, however, although IL-18BP levels
      were not elevated, IL-18 and IL-18BP were found to be positively correlated in
      type 1 diabetics. Even so, free, unbound IL-18 remained significantly increased
      in diabetic patients. Additionally, correlation studies also revealed that IL-18
      and IL-18BP are positively correlated with HbA1c levels in T1D patients,
      suggesting a potential link between IL-18 and metabolic control in these
      patients. Finally, we observed a significant increase in IL-18 protein expression
      within human pancreatic islet specimens collected from type 1 diabetics. These
      results further expand our knowledge of the role of IL-18 in T1D, may give
      insight into common pathogenic mechanisms associated with metabolic control in
      both T1D and T2D, and suggest that targeting this cytokine may improve
      therapeutic outcomes for T1D patients.

PMID- 25576802
TI  - The role of neutrophil gelatinase associated lipocalin (NGAL) as biological
      constituent linking depression and cardiovascular disease.
AB  - Depression is more common in patients with cardiovascular disease than in the
      general population. Conversely, depression is a risk factor for developing
      cardiovascular disease. Comorbidity of these two pathologies worsens prognosis.
      Several mechanisms have been indicated in the link between cardiovascular disease
      and depression, including inflammation. Systemic inflammation can have long
      lasting effects on the central nervous system, which could be associated with
      depression. NGAL is an inflammatory marker and elevated plasma levels are
      associated with both cardiovascular disease and depression. While patients with
      depression show elevated NGAL levels, in patients with comorbid heart failure,
      NGAL levels are significantly higher and associated with depression scores.
      Systemic inflammation evokes NGAL expression in the brain. This is considered a
      proinflammatory effect as it is involved in microglia activation and reactive
      astrocytosis. Animal studies support a direct link between NGAL and
      depression/anxiety associated behavior. In this review we focus on the role of
      NGAL in linking depression and cardiovascular disease. 

PMID- 25576803
TI  - Impact of traumatic brain injury on sleep structure, electrocorticographic
      activity and transcriptome in mice.
AB  - Traumatic brain injury (TBI), including mild TBI (mTBI), is importantly
      associated with vigilance and sleep complaints. Because sleep is required for
      learning, plasticity and recovery, we here evaluated the bidirectional
      relationship between mTBI and sleep with two specific objectives: (1) Test that
      mTBI rapidly impairs sleep-wake architecture and the dynamics of the
      electrophysiological marker of sleep homeostasis (i.e., non-rapid eye movement
      sleep delta (1-4Hz) activity); (2) evaluate the impact of sleep loss following
      mTBI on the expression of plasticity markers that have been linked to sleep
      homeostasis and on genome-wide gene expression. A closed-head injury model was
      used to perform a 48h electrocorticographic (ECoG) recording in mice submitted to
      mTBI or Sham surgery. mTBI was found to immediately decrease the capacity to
      sustain long bouts of wakefulness as well as the amplitude of the time course of
      ECoG delta activity during wakefulness. Significant changes in ECoG spectral
      activity during wakefulness, non-rapid eye movement and rapid eye movement sleep
      were observed mainly on the second recorded day. A second experiment was
      performed to measure gene expression in the cerebral cortex and hippocampus after
      a mTBI followed either by two consecutive days of 6h sleep deprivation (SD) or of
      undisturbed behavior (quantitative PCR and next-generation sequencing). mTBI
      modified the expression of genes involved in immunity, inflammation and glial
      function (e.g., chemokines, glial markers) and SD changed that of genes linked to
      circadian rhythms, synaptic activity/neuronal plasticity, neuroprotection and
      cell death and survival. SD appeared to affect gene expression in the cerebral
      cortex more importantly after mTBI than Sham surgery including that of the
      astrocytic marker Gfap, which was proposed as a marker of clinical outcome after
      TBI. Interestingly, SD impacted the hippocampal expression of the plasticity
      elements Arc and EfnA3 only after mTBI. Overall, our findings reveal alterations
      in spectral signature across all vigilance states in the first days after mTBI,
      and show that sleep loss post-mTBI reprograms the transcriptome in a brain area
      specific manner and in a way that could be deleterious to brain recovery. 

PMID- 25576804
TI  - Colloidal silver nanoparticles improve anti-leukemic drug efficacy via
      amplification of oxidative stress.
AB  - Recently, increased reactive oxygen species (ROS) levels and altered redox status
      in cancer cells have become a novel therapeutic strategy to improve cancer
      selectivity over normal cells. It has been known that silver nanoparticles
      (AgNPs) display anti-leukemic activity via ROS overproduction. Hence, we
      hypothesized that AgNPs could improve therapeutic efficacy of ROS-generating
      agents against leukemia cells. In the current study, N-(4
      hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, was used as a drug model
      of ROS induction to investigate its synergistic effect with AgNPs. The data
      exhibited that AgNPs with uniform size prepared by an electrochemical method
      could localize in the lysosomes, mitochondria and cytoplasm of SHI-1 cells. More
      importantly, AgNPs together with 4-HPR could exhibit more cytotoxicity and
      apoptosis via overproduction of ROS in comparison with that alone. Taken
      together, these results reveal that AgNPs combined with ROS-generating drugs
      could potentially enhance therapeutic efficacy against leukemia cells, thereby
      providing a novel strategy for AgNPs in leukemia therapy. 

PMID- 25576805
TI  - Gold nanoparticles conjugated dopamine as sensing platform for SERS detection.
AB  - In this work, the properties of dopamine and dopamine-quinone on gold
      nanoparticles (Au NPs) surface were studied by the constructed Au NPs/dopamine
      sensing platform using surface enhanced Raman scattering (SERS) spectroscopy.
      Interestingly, the Au NPs/dopamine-quinone exhibited the characteristic Raman
      band at 1270, 1335 and 1480 cm(-1) at pH 10.0, whereas, no obvious Raman band of
      Au NPs/dopamine was observed at pH = 6.0. Also, dopamine-quinone could be reduced
      by glutathione (GSH) and dopamine could be oxidized easily by superoxide radical
      anion (O2(-)), thus, this sensing platform could be used to determine the
      concentration of GSH and O2(-) in a wide range. Importantly, the utility of Au
      NPs/dopamine platform was demonstrated in living HeLa and normal human liver (HL
      7702) cells, and responded to the concentration changes of reactive oxygen
      species (ROS) in real time.

PMID- 25576806
TI  - Sorption and release of drugs in/from cross-linked poly(ethyleneimine) multilayer
      films deposited onto silica microparticles.
AB  - Multilayer thin films are useful materials in fabrication of controlled drug
      delivery systems and in controlling drug release processes. Herein, we report the
      fabrication of single polycation multilayers based on branched poly(ethylene
      imine) (PEI) mediated by dianhydrides (DA), as cross-linker and source of
      carboxylic groups, deposited onto Daisogel silica microparticles, and their
      sorption/release properties for some anionic drugs as a function of the cross
      linker concentration. Pyromellitic dianhydride (PM) and 3,3',4,4'
      benzophenonetetracarboxylic dianhydride (BTCDA) were used as DA reagents. The
      monotonous increase of the (PEI-DA)n multilayers was demonstrated by Fourier
      transform infrared spectroscopy, point of zero charge (pzc), and X-ray
      photoelectron spectroscopy. The sorption properties of the PEI multilayer films
      for two drugs (diclofenac sodium, DS, and indomethacin, IDM) and a model dye
      (Ponceau SS, PSS) were influenced by the number of PEI layers and the weight
      ratio between cross-linker and silica microparticles during the cross-linking
      steps. It was found that the adsorbed amount of drugs increased with the number
      of PEI layers and with the decrease of DA concentration. The Langmuir, Sips, and
      Dubinin-Radushkevich model isotherms were applied to fit the sorption equilibrium
      data of IDM onto the Daisogel//(PEI-DA)n composites. The maximum equilibrium
      sorption capacity, qm, evaluated by the Langmuir model, at 25  degrees C, was
      37.05 mg IDM/g of Daisogel//(PEI-BTCDA)8.5, and 39.99 mg IDM/g of Daisogel//(PEI
      PM)8.5, for a weight percentage of DA/silica of 0.1% w/w. Cumulative release of
      DS was almost 100% within 180 min, while IDM was desorbed at a level of 35%, in
      320 min, supporting a sustained release was gained with the cross-linked PEI
      films. The stability of the (PEI-DA)n multilayers during the successive
      sorption/desorption cycles of PSS was demonstrated.

PMID- 25576807
TI  - Langmuir and Langmuir-Blodgett films of lipids and penicillinase: Studies on
      adsorption and enzymatic activity.
AB  - Bioelectronic devices, such as biosensors, can be constructed with enzymes
      immobilized in ultrathin solid films, for which preserving the enzymatic
      catalytic activity is fundamental for optimal performance. In this sense,
      nanostructured films in which molecular architectures can be controlled are of
      interest. In this present work, the adsorption of the enzyme penicillinase onto
      Langmuir monolayers of the phospholipid dimyristoylphosphatidic acid was
      investigated and characterized with surface pressure-area isotherms and
      polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS).
      The incorporation of the enzyme in the lipid monolayer not only caused the film
      to expand, but also could be identified through amide bands in the PM-IRRAS
      spectra, with the CN and CO dipole moments being identified, lying parallel to
      monolayer plane. Structuring of the enzyme into alpha-helices was identified in
      the mixed enzyme-phospholipid monolayer and preserved when transferred to solid
      as a Langmuir-Blodgett (LB) film. The enzyme-lipid LB films were then
      characterized with PM-IRRAS, atomic force microscopy and fluorescence
      spectroscopy. Measurements of the catalytic activity showed that the enzyme
      accommodated in the LB films preserved 76% of the enzyme activity in relation to
      the homogeneous medium. The method presented here not only allows for enhanced
      catalytic activity toward penicillin, but also can be useful to explain why
      certain film architectures exhibit better enzyme activity. 

PMID- 25576808
TI  - Characterization of the modified chitosan membrane cross-linked with genipin for
      the cultured corneal epithelial cells.
AB  - OBJECTIVES: To modify a chitosan membrane (CM) by cross-linking the chitosan with
      genipin, a naturally occurring cross-linker extracted from Gardenia jasminoides
      fructus, with the aim of developing a new cell culture support and to observe the
      phenotypes of cultured human corneal epithelial cells (HCECs) on genipin-cross
      linked chitosan membrane (GCM). METHODS: We tested the cross-linking
      characteristics and mechanical strength of the GCM. CMs modified by cross-linking
      with different concentrations of genipin were prepared to investigate the rate of
      membrane degradation. The biocompatibility of the GCMs was investigated by
      determining the viability of HCECs cultured on them in vitro. The morphology of
      the HCECs cultured on CM or GCM was analyzed by confocal microscopy and scanning
      electron microscopy (SEM). Immunocytochemical staining was conducted to determine
      the phenotypes of the cultured cells. RESULTS: The fixation index of the GCM was
      31 +/- 3% after treatment of CM with 0.5mM genipin. A stress-strain test showed
      that the GCM could tolerate three times the mechanical force of noncross-linked
      CM. The biodegradation rate of GCM was much slower than for CM. A 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay showed that
      cell viability was not affected by cross-linking with 5.0mM genipin. SEM showed
      that the cultured HCECs adhered to and grew well on the surface of the GCM.
      Immunocytochemical staining showed keratin 3 (K3) and connexin 43 (Cx-43)
      immunoreactive HCECs on the GCM and their proliferative ability was not
      significantly affected by strong immunoreactivity of Ki-67 and p63 markers.
      CONCLUSIONS: GCM has potential as a scaffold for corneal epithelium in ocular
      surface surgery and greater mechanical strength and slower degradation than
      unmodified CM.

PMID- 25576809
TI  - Rational design of didodecyldimethylammonium bromide-based nanoassemblies for
      gene delivery.
AB  - Nonviral gene vectors are a hot topic for gene delivery. High cost and low
      transfection efficiency hinder the application of them. The aim of this study was
      to find out the optimal gene vectors with lower cost and more effective gene
      delivery than commonly used gene vectors. A cheap cationic lipid,
      didodecyldimethylammonium bromide (DDAB) was the basic component and the other
      components included oleic acid (OA), cholesterol (Chol), cholesteryl succinyl
      poly(ethylene glycol) 1500 (CHS-PEG), poly(D,L-lactide-co-glycolide)-methoxy
      poly(ethylene glycol) (PLGA-PEG). The combinations of DDAB/OA/Chol, DDAB/OA/CHS
      PEG and DDAB/PLGA-PEG were adopted to prepare the nanoassemblies named CNA, CPNA
      and PPNA, respectively. The optimal component ratios were screened out according
      to their Langmuir monolayer behavior. The optimal preparation method of
      nanoassemblies involved firstly compressing DNA or siRNA with the cationic lipid
      (DDAB) and secondly being coated with the helper lipids (OA and CHS-PEG) or the
      helper polymer (PLGA-PEG). The complexes of genes and cationic lipids were
      encapsulated into the core of CPNA and PPNA. The optimal gene vectors (CPNA and
      PPNA) with small sizes, low negative surface charges and non-exposure of cationic
      lipids were achieved. They had the advantages of no cytotoxicity, high
      transfection efficiency and low cost. More importantly, CPNA and PPNA were not
      sensitive to serum and showed the similar or higher transfection efficiency of
      pDNA and siRNA compared to Lipofectamine 2000. CPNA could mainly enter cell
      plasma based on endocytosis. The rational design method is useful for the design
      and optimization of DDAB-based gene carriers and other cationic lipid-based
      carriers.

PMID- 25576810
TI  - Gold nanoparticle incorporated polymer/bioactive glass composite for controlled
      drug delivery application.
AB  - The present study discusses the development of a biodegradable polymer
      encapsulated-nanogold incorporated-bioactive glass composite (AuPBG) by a low
      temperature method. The composite was analyzed by atomic force microscopy (AFM),
      X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy,
      thermogravimetry (TG), fluorescence and dissolution analysis. The composite
      exhibited aggregation behaviour in solid and solution states and exhibited
      negative zeta potential (-13.3 +/- 1.4 mV). The composite exhibited fast
      degradation starting from the 5(th) day onwards in phosphate buffered saline
      (PBS) for a period of 14 days. The composite showed fluorescence quenching effect
      at pH 7 and the fluorescence recovered at pH 5. The composite has been found to
      be suitable for the release of doxorubicin at high rates at acidic pH (~ 5) which
      is the intracellular pH of tumour cells. The drug loading ratio is also high and
      it exhibited a controlled release for a period of 8 days in PBS. The system
      serves as a promising material for targeted drug delivery applications.

PMID- 25576811
TI  - Green-step assembly of low density lipoprotein/sodium carboxymethyl cellulose
      nanogels for facile loading and pH-dependent release of doxorubicin.
AB  - In this study, a simple and green approach was developed to produce a novel
      nanogel via self-assembly of low density lipoproteins (LDL) and sodium
      carboxymethyl cellulose (CMC), to efficiently deliver doxorubicin (DOX) to cancer
      cells. Under optimal conditions, the stable nanogels were of spherical shape with
      an average diameter of about 90 nm, PDI<0.3 and a zeta potential -35 mV.
      Furthermore, the cationic anticancer drug, doxorubicin (DOX) was effectively
      encapsulated into LDL/CMC nanogels with an exceptionally high encapsulation
      efficiency of ~ 98%. The release of DOX from DOX-LDL/CMC nanogels was pH
      dependent, and DOX was released at a quicker rate at pH 6.2 than at pH 7.4.
      Importantly, the DOX-LDL/CMC nanogels were shown to effectively kill cancer cells
      in vitro. The IC50 of the DOX-LDL/CMC nanogels in HeLa and HepG2 cells was
      approximately 2.45 and 1.72 times higher than that of free DOX. The slightly
      reduced antitumor efficacy was primarily due to the less cellular uptake of the
      DOX-LDL/CMC nanogels, which was confirmed by confocal laser scanning microscope
      (CLSM) and flow cytometry analysis. The high DOX payload and pH-dependent drug
      release rendered LDL/CMC nanogels as an efficient carrier for doxorubicin and
      possibly be used for other cationic drugs in different biomedical applications.

PMID- 25576813
TI  - Phospatidylserine or ganglioside--which of anionic lipids determines the effect
      of cationic dextran on lipid membrane?
AB  - In this work the influence of cationic polymer, namely diethylaminoethyl DEAE
      dextran on model lipid membranes was investigated. This polymer is of a wide
      application as a biomaterial and a drug carrier and its cytotoxicity toward
      various cancer cells was also confirmed. It was suggested that anticancer effect
      of cationic dextran is connected with the binding of the polymer to the
      negatively charged sialic acid residues overexpressed in cancer membrane. This
      fact encouraged us to perform the studies aimed at verifying whether the effect
      of cationic DEAE-dextran on membrane is determined only by the presence of the
      negatively charged lipid in the system or the kind of anionic lipid is also
      important. To reach this goal systematic investigations on the effect of dextran
      on various one-component lipid monolayers and multicomponent hepatoma cell model
      membranes differing in the level and the kind of anionic lipids
      (phosphatidylserine, sialic acid-containing ganglioside GM3 or their mixture)
      were done. As evidenced the results the effect of DEAE-dextran on the model
      system is determined by anionic lipid-polymer electrostatic interactions.
      However, the magnitude of the effect of cationic polymer is strongly dependent on
      the kind of anionic lipid in the model system. Namely, the packing and ordering
      of the mixtures containing ganglioside GM3 were more affected by DEAE-dextran
      than phosphatidylserine-containing monolayers. Although the experiments were done
      on model systems and therefore further studies are highly needed, the collected
      data may indicate that ganglioside may be important in the differentiation of the
      effect of cationic dextran on membranes. 

PMID- 25576812
TI  - Formulation of glutathione responsive anti-proliferative nanoparticles from
      thiolated Akt1 siRNA and disulfide-crosslinked PEI for efficient anti-cancer gene
      therapy.
AB  - In this study, thiol-modified siRNA (SH-siRNA) was delivered by bioreducible
      polyethylenimine (ssPEI), to enhance physicochemical properties of polyplexes and
      function of siRNA through disulfide bonding between SH-siRNA and ssPEI. The ssPEI
      was utilized to deliver Akt1 SH-siRNA for suppression of Akt1 mRNA and blockage
      of Akt1 protein translation, resulting in reduced cellular proliferation and the
      induction of apoptosis. Disulfide bondings between the ssPEI and SH-siRNA through
      thiol groups in both were confirmed by DTT treatment. Complexation between ssPEI
      and Akt1SH-siRNA was enhanced and reduced surface charge of ssPEI/Akt1SH-siRNA
      complexes with smaller average particle sizes even at lower N/P ratios was
      obtained compared with PEI/Akt1siRNA ones. Cellular uptake of ssPEI/Akt1SH-siRNA
      complexes in CT-26 mouse colon cancer cells was also enhanced. The ssPEI/Akt1SH
      siRNA complexes reduced proliferation and increased apoptosis of mouse colon
      cancer cells in vitro. In an in vivo mouse tumor model, the complexes reduced
      tumor proliferation and downregulation of Akt1 compared to controls. 

PMID- 25576814
TI  - Reduction-sensitive amphiphilic copolymers made via multi-component Passerini
      reaction for drug delivery.
AB  - One-step synthesis of amphiphilic polymers containing disulfide bond within the
      hydrophobic backbone was demonstrated via multi-component Passerini reaction. The
      obtained polymer was self-assembled into micelles in aqueous solution. Curcumin
      (CUR), an effective and safe anticancer agent, which was limited by its water
      insolubility and poor bioavailability, was loaded into the micelles as a model
      drug. The nanoscale polymeric micelles were confirmed by dynamic light scattering
      (DLS) and transmission electron microscopy (TEM). Faster intracellular CUR
      release was observed by confocal laser scanning microscopy (CLSM) in the HeLa
      cells pretreated with GSH than in the unpretreated ones. Micelles also loaded
      with NH2-BODIPY which was almost non-fluorescent and gave strong enhanced
      fluorescence under acid conditions. The phenomenon of the stronger enhanced
      fluorescence in the pretreated HeLa cells showed further that the obtained
      polymer was reduction-sensitive. In vitro MTT assays showed that the micelles
      were biocompatible and CUR-loaded micelles had higher cellular proliferation
      inhibition in contrast to free CUR toward HeLa cells. These results highlight the
      potential of using multi-component Passerini reaction to make functional
      copolymers as smart nanocarriers for drug delivery. 

PMID- 25576815
TI  - Bacterial (BKH1) assisted silica nanoparticles from silica rich substrates: a
      facile and green approach for biotechnological applications.
AB  - A green technique of silica nanoparticles (SiO2-NPs) formation by using a
      thermophilic bacterium (BKH1) as biological template is demonstrated here. SiO2
      NPs are synthesized from inorganic (magnesium tri-silicate), and organic
      (tetraethyl orthosilicate) precursor with the help of BKH1 bacteria. BKH1 derived
      SiO2-NPs are subjected to Atomic Force Microscopy, Transmission Electron
      Microscopy, and Field Emission Scanning Electron Microscopy equipped with Energy
      Dispersive X-ray Analyzer to establish nanoparticle morphology. In addition,
      Infrared Spectroscopy reveals the presence of chemical and functional groups in
      SiO2-NPs samples and X-ray diffraction, the amorphous nature. The Zeta potential
      (zeta) reveals substantial stability of bacteria derived SiO2-NPs in the aqueous
      environment. Presence of two intense luminescence peaks in the UV and visible
      regions merits the bacteria derived SiO2-NPs for use as an optical probe in
      biomedical applications. This novel mode of bacteria derived SiO2-NPs formation
      is eco-friendly and ambient temperature synthesis approach. It avoids the complex
      protocol of multi-steps synthesis of silica nanoparticles, hence likely to be
      cost-effective. In-depth translation research is suggested for the synthesis of
      silica nanoparticles in large quantities using thermophilic BKH1 template. 

PMID- 25576816
TI  - Functional short-chain zwitterion coated silica nanoparticles with antifouling
      property in protein solutions.
AB  - A new functional nanoparticle, consisting of a silica core onto which short-chain
      zwitterions are chemically connected, was successfully prepared and showed
      excellent antifouling performance to protein solutions. These nanoparticles (NPs)
      own excellent stability even in 1M NaCl solutions for at least 48 h. The
      interaction between these "zwitterated" NPs and proteins were investigated by
      dynamic light scattering (DLS), turbidimetric titration, and isothermal titration
      calorimetry (ITC). The results demonstrated that the zwitterated NPs had
      antifouling property both in single protein solutions and serum (fetal bovine
      serum, FBS). The zwitterated NPs also own abundant functional groups which could
      conjugate with biomolecules for future applications in therapeutic and diagnostic
      field.

PMID- 25576817
TI  - One-pot preparation of cross-linked amphiphilic fluorescent polymer based on
      aggregation induced emission dyes.
AB  - Facile one-pot preparation of cross-linked amphiphilic fluorescent polymer based
      on aggregation induced emission (AIE) dyes and 2-isocyanatoethyl methacrylate
      (IM) has been developed. This was carried out first by free radical
      polymerization between AIE monomer (PhE) and IM, and then polyethyleneimine (PEI)
      was introduced to obtain the cross-linked fluorescent polymer. The resulted cross
      linked amphiphilic polymer was prone to self-assemble into stable nanoparticles
      in aqueous solution with surplus amino groups on the surface which made them
      highly water dispersible and can be further functionalized. The as-prepared
      fluorescent polymer nanoparticles (PhE-IM-PEI FPNs) were fully characterized by a
      series of techniques including (1)H NMR spectrum, X-ray photoelectron
      spectroscopy, Fourier transform infrared spectroscopy, transmission electron
      microscopy, dynamic light scattering, UV-vis absorption spectrum, and
      fluorescence spectra. Such FPNs demonstrated intense orange fluorescence with a
      high quantum yield of about 40%. Biocompatibility evaluation and cell uptake
      behavior of the nanoparticles were further investigated to explore their
      potential biomedical applications; the demonstrated excellent biocompatibility
      made them promising for cell imaging. 

PMID- 25576819
TI  - Reply: To PMID 25139139.

PMID- 25576818
TI  - Previous prelabor or intrapartum cesarean delivery and risk of placenta previa.
AB  - OBJECTIVE: The purpose of this study was to examine the association between
      previous cesarean delivery and subsequent placenta previa while distinguishing
      cesarean delivery before the onset of labor from intrapartum cesarean delivery.
      STUDY DESIGN: We conducted a retrospective cohort study of electronic medical
      records from 20 Utah hospitals (2002-2010) with restriction to the first 2
      singleton deliveries of nulliparous women at study entry (n=26,987). First
      pregnancy delivery mode was classified as (1) vaginal (reference), (2) cesarean
      delivery before labor onset (prelabor), or (3) cesarean delivery after labor
      onset (intrapartum). Risk of second delivery previa was estimated by previous
      delivery mode with the use of logistic regression and was adjusted for maternal
      age, insurance, smoking, comorbidities, previous pregnancy loss, and history of
      previa. RESULTS: Most first deliveries were vaginal (82%; n=22,142), followed by
      intrapartum cesarean delivery (14.6%; n=3931), or prelabor cesarean delivery
      (3.4%; n=914). Incidence of second delivery previa was 0.29% (n=78) and differed
      by previous delivery mode: vaginal, 0.24%; prelabor cesarean delivery, 0.98%;
      intrapartum cesarean delivery, 0.38% (P<.001). Relative to vaginal delivery,
      previous prelabor cesarean delivery was associated with an increased risk of
      second delivery previa (adjusted odds ratio, 2.62; 95% confidence interval, 1.24
      5.56). There was no significant association between previous intrapartum cesarean
      delivery and previa (adjusted odds ratio, 1.22; 95% confidence interval, 0.68
      2.19). CONCLUSION: Previous prelabor cesarean delivery was associated with a >2
      fold significantly increased risk of previa in the second delivery, although the
      approximately 20% increased risk of previa that was associated with previous
      intrapartum cesarean delivery was not significant. Although rare, the increased
      risk of placenta previa after previous prelabor cesarean delivery may be
      important when considering nonmedically indicated prelabor cesarean delivery.

PMID- 25576820
TI  - Pregnancy induces persistent changes in vascular compliance in primiparous women.
AB  - OBJECTIVE: Pregnancy induces rapid, progressive, and substantial changes to the
      cardiovascular system. The low recurrence risk of preeclampsia, despite familial
      predisposition, suggests an adaptation associated with pregnancy that attenuates
      the risk for subsequent preeclampsia. We aimed to evaluate the persistent effect
      of pregnancy on maternal cardiovascular physiology. STUDY DESIGN: Forty-five
      healthy nulliparous women underwent baseline cardiovascular assessment before
      conception and repeated an average of 30 months later. After baseline evaluation,
      17 women conceived singleton pregnancies and all delivered at term. The remaining
      28 women comprised the nonpregnant control group. We measured mean arterial blood
      pressure, cardiac output, plasma volume, pulse wave velocity, uterine blood flow,
      and flow-mediated vasodilation at each visit. RESULTS: There was a significant
      decrease in mean arterial pressure from the prepregnancy visit to postpartum in
      women with an interval pregnancy (prepregnancy, 85.3+/-1.8; postpartum, 80.5+/
      1.8 mm Hg), with no change in nonpregnant control subjects (visit 1, 80.3+/-1.4;
      visit 2, 82.8+/-1.4 mm Hg) (P=.002). Pulse wave velocity was significantly
      decreased in women with an interval pregnancy (prepregnancy, 2.73+/-0.05;
      postpartum, 2.49+/-0.05 m/s), as compared with those without an interval
      pregnancy (visit 1, 2.56+/-0.04; visit 2, 2.50+/-0.04 m/s) (P=.005). We did not
      observe a residual effect of pregnancy on cardiac output, plasma volume, uterine
      blood flow, or flow-mediated vasodilation. CONCLUSION: Our observations of
      decreased mean arterial pressure and reduced arterial stiffness following
      pregnancy suggest a significant favorable effect of pregnancy on maternal
      cardiovascular remodeling. These findings may represent a mechanism by which
      preeclampsia risk is reduced in subsequent pregnancies.

PMID- 25576821
TI  - The effect of maternal sleep-disordered breathing on the infant's
      neurodevelopment.
AB  - OBJECTIVE: We sought to examine the effect of maternal sleep-disordered breathing
      (SDB) on infant general movements (GMs) and neurodevelopment. STUDY DESIGN:
      Pregnant women with uncomplicated full-term pregnancies and their offspring were
      prospectively recruited from a community and hospital low-risk obstetric
      surveillance. All participants completed a sleep questionnaire on second
      trimester and underwent ambulatory sleep evaluation (WatchPAT; Itamar Medical,
      Caesarea, Israel). They were categorized as SDB (apnea hypopnea index>5) and
      controls. Infant GMs were assessed in the first 48 hours and at 8-11 and 14-16
      weeks of age. At 12 months of age the Infant Developmental Inventory and the
      Brief Infant Sleep Questionnaire were administered. RESULTS: In all, 74 women and
      their full-term infants were studied. Eighteen (24%) women had SDB. Mean
      birthweight was 3347.1+/-423.9 g. Median Apgar score at 5 minutes was 10 (range,
      8-10). In adjusted comparisons, no differences were found between infants born to
      mothers with SDB and controls in GM scores in all 3 evaluations. Low social
      developmental score was detected at 12 months in 64% of infants born to SDB
      mothers compared to 25% of infants born to controls (adjusted P=.036; odds ratio,
      16.7). Infant snoring was reported by 41.7% of mothers with SDB compared to 7.5%
      of controls (P=.004). CONCLUSION: Our preliminary results suggest that maternal
      SDB during pregnancy has no adverse effect on neonatal and infant neuromotor
      development but may affect social development at 1 year.

PMID- 25576822
TI  - Response to the "Viewpoint" article regarding thyroid-screening in pregnancy.

PMID- 25576823
TI  - Impact of an urban multi-metal contamination gradient: metal bioaccumulation and
      tolerance of river biofilms collected in different seasons.
AB  - The aim of this study was to investigate the repeatability and seasonal
      variability of the biological response of river biofilms chronically exposed to a
      multi-metal pressure in an urban contamination gradient. Biofilms were grown on
      immersed plastic membranes at three sites on the Seine river upstream (site 1)
      and downstream (sites 2 and 3) from Paris (France). They were collected in four
      different seasons (autumn, spring, summer and winter). Biofilm tolerance to Cu,
      Ni, Pb and Zn was measured using a PICT (Pollution-Induced Community Tolerance)
      approach with a previously developed short-term toxicity test based on beta
      glucosidase (heterotrophic) activity. Metal concentrations in the river and also
      in the biofilm samples (total and non-exchangeable bioaccumulated metals) were
      also monitored. Biofilm-accumulated metal concentrations reflected the increase
      of the multi-metal exposure along the urban gradient. These concentrations were
      strongly correlated with dissolved and particulate organic carbon and with the
      total metal fraction in the river water, which recalls the significant influence
      of the environmental parameters on metal uptake processes in river biofilms.
      Overall, natural biofilms allow monitoring water quality by integrating the
      variations of a diffuse metal contamination overtime. Tolerance levels globally
      increased from site 1 to site 3 reflecting the metal pollution gradient measured
      in the river water collected at the three sites. Cu tolerance tended to increase
      during warm seasons but no clear seasonal tendency could be found for Ni, Pb and
      Zn. Furthermore, principal component analysis clearly discriminated samples
      collected upstream (site 1) from samples collected downstream (sites 2 and 3)
      along the first principal component which was correlated to the metal gradient.
      Samples collected in winter were also separated from the others along the second
      principal component correlated to parameters like water temperature and Total
      Suspended Solids concentration. This study shows that chronic in situ exposure to
      environmental metal concentrations has a significant impact on natural biofilms.
      Biofilm tolerance to metals and biofilm metal bioaccumulation both reflect metal
      exposure levels although they remain low when compared to Environmental Quality
      Standards from the European Water Framework Directive. Yet temperature appears as
      an important environmental variable shaping community structure and response to
      toxic exposure which shows that the sampling date is an important parameter to
      consider when using natural river biofilms to assess the impacts of urban
      pressure. 

PMID- 25576824
TI  - Functional characterisation of a TLR accessory protein, UNC93B1, in Atlantic
      salmon (Salmo salar).
AB  - Toll-like receptors (TLRs) are indispensable components of the innate immune
      system, which recognise conserved pathogen associated molecular patterns (PAMPs)
      and induce a series of defensive immune responses to protect the host.
      Biosynthesis, localisation and activation of TLRs are dependent on TLR accessory
      proteins. In this study, we identified the accessory protein, UNC93B1, from
      Atlantic salmon (Salmo salar) whole-genome shotgun (WGS) contigs aided by the
      conserved gene synteny of genes flanking UNC93B1 in fish, birds and mammals.
      Phylogenetic analysis showed that salmon UNC93B1 grouped with other vertebrate
      UNC93B1 molecules, and had highest amino acid identity and similarity to
      zebrafish UNC93B1. The salmon UNC93B1 gene organisation was also similar in
      structure to mammalian UNC93B1. Our gene expression studies revealed that salmon
      UNC93B1 was more highly expressed in spleen, liver and gill tissues but was
      expressed at a lower level in head kidney tissue in post-smolts relative to parr.
      Moreover, salmon UNC93B1 mRNA transcripts were up-regulated in vivo in spleen
      tissue from polyI:C treated salmon and in vitro in polyI:C or IFNgamma stimulated
      Salmon Head Kidney-1 (SHK-1) cells. Initial studies into the functional role of
      salmon UNC93B1 in fish TLR signalling found that both wild type salmon UNC93B1
      and a molecule with a site-directed mutation (H424R) co-immunoprecipitated with
      salmon TLR19, TLR20a and TLR20d. Overall, these data illustrate the potential
      importance of UNC93B1 as an accessory protein in fish TLR signalling. 

PMID- 25576825
TI  - Profile of infective endocarditis at a tertiary-care hospital in Japan over a 14
      year period: characteristics, outcome and predictors for in-hospital mortality.
AB  - OBJECTIVES: The aims of this study were to describe the epidemiological features
      and clinical characteristics of infective endocarditis (IE) at a tertiary-care
      hospital in Japan and to identify the factors associated with in-hospital
      mortality. METHODS: A retrospective observational study was conducted at a 925
      bed tertiary-care teaching hospital in Japan. All adult patients diagnosed with
      definite IE between August 2000 and July 2014 according to the modified Duke
      criteria were included. RESULTS: A total of 180 patients (60.6% men; mean age,
      69.1 years) with definite IE were included. The most common pathogen was
      Staphylococcus aureus (27.2%). Nine patients (5.0%) had culture-negative IE.
      Transthoracic and transoesophageal echocardiography were performed in 180 (100%)
      and 132 patients (73.3%), respectively, and vegetations were detected in 128
      patients (71.1%). Surgical therapy was performed in 31 patients (17.2%). Overall,
      the in-hospital mortality rate was 26.1%. The independent predictors of in
      hospital mortality were methicillin-resistant S. aureus (MRSA), vascular
      phenomena, health care-associated IE and heart failure. CONCLUSIONS: MRSA,
      vascular phenomena, health care-associated IE and heart failure were independent
      predictors of in-hospital mortality. The unique characteristics in our cohort
      were the very high mean age, low rate of culture-negative IE, high rate of
      definite IE without detected vegetations and predominance of S. aureus.

PMID- 25576826
TI  - Patterns of anemia during malaria.

PMID- 25576827
TI  - Probable Crimean-Congo hemorrhagic fever virus transmission occurred after
      aerosol-generating medical procedures in Russia: nosocomial cluster.
AB  - We report here a fatal case of laboratory confirmed Crimean-Congo hemorrhagic
      fever (CCHF), which caused nosocomial infection in eight health care workers
      (HCWs), who had provided medical care for the patient. All the HCWs survived. The
      report demonstrates that airborne transmission of CCHF is a real risk, at least
      when the CCHF patient is in a ventilator. During performance of any aerosol
      generating medical procedures for any CCHF patient airborne precautions should
      always be added to standard precautions, in particular, airway protective N95
      mask or equivalent standard, eye protection, single airborne precaution room, or
      a well-ventilated setting. 

PMID- 25576828
TI  - Insight into the structural flexibility and function of Mycobacterium
      tuberculosis isocitrate lyase.
AB  - Isocitrate lyase (ICL), is a key enzyme of the glyoxylate shunt crucial for the
      survival of Mycobacterium tuberculosis (Mtb) in macrophages during persistent
      infection. MtbICL catalyses the first step of this carbon anaplerosis cycle and
      is considered as a potential anti-tubercular drug target. The MtbICL is a
      tetramer with 222 symmetry, and each subunit of the enzymeis composed of 14 alpha
      helices and 14 beta-strands. We studied the conformational flexibility of the
      enzyme to get a deeper insight into its stability and function. Our studies show
      that the mutation of His180, close to the MtbICL signature sequence (K193KCGH197)
      completely abolishes the oligomeric conformation and function of the enzyme.
      Molecular dynamics studies suggest that the loss of interaction between His180
      and Tyr89 most likely alters the orientation of Tyr89 side chain, thereby causing
      the movement of helices alpha6, alpha12, alpha13 and alpha14 in the vicinity and
      affecting the tetrameric assembly. We further show that the oligomerization of
      MtbICL is primarily mediated by the inter subunit interactions, and strengthened
      by the helix swapping of alpha12-alpha13 between adjacent subunits. Furthermore,
      the enzyme activity is influenced by the interactions between the residues of lid
      region (P411NSSTTALTGSTEEGQFH428) and the loop region (T391KHQREV397). Mutation
      of glutamates of the lid region to non homologous residues (E423A or E424A) or
      basic residues (E423K or E424K) inactivates the enzyme, whereas the activity is
      not much compromised in case of homologous mutations (E423D or E424D). 

PMID- 25576829
TI  - Phenotypic characterization and complementation analysis of Bacillus subtilis 6S
      RNA single and double deletion mutants.
AB  - 6S RNA, a global regulator of transcription in bacteria, binds to housekeeping
      RNA polymerase (RNAP) holoenzymes to competitively inhibit transcription from DNA
      promoters. Bacillus subtilis encodes two 6S RNA homologs whose differential
      functions are as yet unclear. We constructed derivative strains of B. subtilis
      PY79 lacking 6S-1 RNA (DeltabsrA), 6S-2 RNA (DeltabsrB) or both (DeltabsrAB) to
      study the physiological role of the two 6S RNAs. We observed two growth
      phenotypes of mutant strains: (i) accelerated decrease of optical density toward
      extended stationary phase and (ii) faster outgrowth from stationary phase under
      alkaline stress conditions (pH 9.8). The first phenotype was observed for
      bacteria lacking bsrA, and even more pronounced for DeltabsrAB bacteria, but not
      for those lacking bsrB. The magnitude of the second phenotype was relatively weak
      for DeltabsrB, moderate for DeltabsrA and again strongest for DeltabsrAB
      bacteria. Whereas DeltabsrAB bacteria complemented with bsrB or bsrA (strains
      DeltabsrAB + B and DeltabsrAB + A) mimicked the phenotypes of the DeltabsrA and
      DeltabsrB strains, respectively, complementation with the gene ssrS encoding
      Escherichia coli 6S RNA failed to cure the "low stationary optical density"
      phenotype of the double mutant, despite ssrS expression, in line with previous
      findings. Finally, proteomics (two-dimensional differential gel electrophoresis,
      2D-DIGE) of B. subtilis 6S RNA deletion strains unveiled a set of proteins that
      were expressed at higher levels particularly during exponential growth and
      preferentially in mutant strains lacking 6S-2 RNA. Several of these proteins are
      involved in metabolism and stress responses. 

PMID- 25576830
TI  - Dose-response estrogen promotes osteogenic differentiation via GPR40 (FFAR1) in
      murine BMMSCs.
AB  - Estrogen plays an essential role in bone formation, and estrogen modulation
      dysfunction is tightly associated with postmenopausal osteoporosis (PMOP). The
      underlying mechanisms of estrogen-mediated osteogenic differentiation have not
      been well defined. In this study, murine bone marrow mesenchymal stem cells were
      induced to undergo osteogenic differentiation, and gene expression analysis or
      GPR40 expression manipulation was performed. Bilateral ovariectomized or sham
      operated C57BL/6 mice were administered GPR40 agonist (GW9508) for bone mineral
      density analysis. We identified GPR40, a long chain unsaturated fatty acid
      receptor, to be regulated by estrogen and involved in osteogenic differentiation
      both in vivo and in vitro. Mechanistically, the Wnt/beta-catenin signaling
      pathway is essential for GPR40 to promote osteogenic differentiation.
      Furthermore, in vivo GW9508 administration rescued estrogen-deficient bone loss,
      indicating the essential role of the GPR40 receptor. To our knowledge, this is
      the first study that provides evidence for GPR40 as a positive regulator of
      osteogenesis and Wnt/beta-catenin signaling. These results indicate that GPR40
      may function as an endogenous promoter of estrogen-induced osteogenic
      differentiation through Wnt/beta-catenin signaling activation. Therefore, as the
      global population of ages and the prevalence of metabolic-related disorders,
      especially PMOP, increases, our findings suggest that GPR40 is a key in
      understanding the link between bone and fat. It may also be a useful target for
      the treatment of bone complications in the future. 

PMID- 25576831
TI  - Anticoagulant mechanism and platelet deaggregation property of a non-cytotoxic,
      acidic phospholipase A2 purified from Indian cobra (Naja naja) venom: inhibition
      of anticoagulant activity by low molecular weight heparin.
AB  - In the present study, anticoagulant and platelet modulating activities of an
      acidic phospholipase A2 (NnPLA2-I) purified from Indian cobra Naja naja venom was
      investigated. The NnPLA2-I displayed a mass of 15.2 kDa and 14,186.0 Da when
      analyzed by SDS-PAGE and MALDI-TOF-MS, respectively. Peptide mass fingerprinting
      analysis of the NnPLA2-I showed its significant similarity with phospholipase A2
      enzymes purified from cobra venom. BLAST analysis of one tryptic peptide sequence
      of NnPLA2-I demonstrated putative conserved domains of the PLA2-like superfamily.
      The Km and Vmax values of NnPLA2-I toward hydrolysis of its most preferred
      substrate-phosphotidylcholine (PC)-were determined to be 0.72 mM and 29.3 MUmol
      min(-1) mg(-1), respectively. The anticoagulant activity of NnPLA2-I was found to
      be higher than the anticoagulant activity of heparin/AT-III or warfarin. The
      histidine modifying reagent, monovalent and polyvalent antivenom differentially
      inhibited the catalytic and anticoagulant activities of NnPLA2-I. Low molecular
      weight heparin did not inhibit the catalytic and platelet deaggregation activity
      of NnPLA2-I, albeit its anticoagulant activity was significantly reduced. The
      NnPLA2-I showed a non-enzymatic, mixed inhibition of thrombin with a Ki value of
      9.3 nM. Heparin significantly decreased, with an IC50 value of 15.23 mIU, the
      thrombin inhibitory activity of NnPLA2-I. The NnPLA2-I uniquely increased the
      amidolytic activity of FXa without influencing its prothrombin activating
      property. NnPLA2-I showed dose-dependent deaggregation of platelet rich plasma
      (PRP) and inhibited the collagen and thrombin-induced aggregation of PRP.
      However, deaggregation of washed platelets by NnPLA2-I demonstrated in presence
      of PC or platelet poor plasma. Alkylation of histidine residue of NnPLA2-I
      resulted in 95% and 21% reduction of its platelet deaggregation and platelet
      binding properties, respectively. NnPLA2-I did not show cytotoxicity against
      human glioblastoma U87MG cells, bactericidal or hemolytic activity. The future
      therapeutic application of NnPLA2-I for treatment and prevention of
      cardiovascular disorders is therefore suggested.

PMID- 25576832
TI  - Mechanistic insights into the inhibitory effects of palmitoylation on cytosolic
      thioredoxin reductase and thioredoxin.
AB  - Overnutrition can lead to oxidative stress, but its underlying mechanism remains
      unclear. In this study, we report that human liver-derived HepG2 cells utilize
      cytosolic thioredoxin reductase (TrxR1) and thioredoxin (hTrx1) to defend against
      the high glucose/palmitate-mediated increase in reactive oxygen species. However,
      enhanced TrxR1/hTrx1 palmitoylation occurs in parallel with a decrease in their
      activities under the conditions studied here. An autoacylation process appears to
      be the major mechanism for generating palmitoylated TrxR1/Trx1 in HepG2 cells. A
      novel feature of this post-translational modification is the covalent inhibition
      of TrxR1/hTrx1 by palmitoyl-CoA, an activated form of palmitate. The palmitoyl
      CoA/TrxR1 reaction is NADPH-dependent and produces palmitoylated TrxR1 at an
      active site selenocysteine residue. Conversely, S-palmitoylation occurs at the
      structural Cys62/Cys69/Cys72 residues but not the active site Cys32/Cys35
      residues of hTrx1. Palmitoyl-CoA concentration and the period of incubation with
      TrxR1/hTrx1 are important factors that influence the inhibitory efficacy of
      palmitoyl-CoA on TrxR1/hTrx1. Thus, an increase in TrxR1/hTrx1 palmitoylation
      could be a potential consequence of high glucose/palmitate. The time-dependent
      inactivation of the NADPH-TrxR1-Trx1 system by palmitoyl-CoA occurs in a biphasic
      manner - a fast phase followed by a slow phase. Kinetic analysis suggests that
      the fast phase is consistent with a fast and reversible association between
      TrxR1/hTrx1 and palmitoyl-CoA. The slow phase is correlated with a slow and
      irreversible inactivation, in which selenolate/thiolate groups nucleophilically
      attack the alpha-carbon of bound palmitoyl-CoA, leading to the formation of
      thioester/selenoester bonds. hTrx1 can enhance rate of fast phase but limits the
      rate of slow phase when it is present in a preincubation mixture containing
      NADPH, TrxR1 and palmitoyl-CoA. Therefore, hTrx1 may provide palmitoylation sites
      or partially protect the TrxR1 active site selenol/thiol group(s) from
      palmitoylation. Our data suggest that Se/S-palmitoylation acts as an important
      modulator of TrxR1/hTrx1 activities, representing a novel potential mechanism
      that underlies overnutrition-induced events. 

PMID- 25576833
TI  - Activation of p53 mediated glycolytic inhibition-oxidative stress-apoptosis
      pathway in Dalton's lymphoma by a ruthenium (II)-complex containing 4-carboxy N
      ethylbenzamide.
AB  - There is a general agreement that most of the cancer cells switch over to aerobic
      glycolysis (Warburg effect) and upregulate antioxidant enzymes to prevent
      oxidative stress induced apoptosis. Thus, there is an evolving view to target
      these metabolic alterations by novel anticancer agents to restrict tumor
      progression in vivo. Previously we have reported that when a non toxic dose (10
      mg/kg bw i.p.) of a novel anticancer ruthenium(II)-complex containing 4-carboxy N
      ethylbenzamide; Ru(II)-CNEB, was administered to the Dalton's lymphoma (DL)
      bearing mice, it regressed DL growth by inducing apoptosis in the DL cells. It
      also inactivated M4-LDH (M4-lactate dehydrogenase), an enzyme that drives
      anaerobic glycolysis in the tumor cells. In the present study we have
      investigated whether this compound is able to modulate regulation of glycolytic
      inhibition-apoptosis pathway in the DL cells in vivo. We observed that Ru(II)
      CNEB could decline expression of the inducible form of 6-phosphofructo-2-kinase
      (iPFK2: PFKFB3), the master regulator of glycolysis in the DL cells. The complex
      also activated superoxide dismutase (the H2O2 producing enzyme) but declined the
      levels of catalase and glutathione peroxidase (the two H2O2 degrading enzymes) to
      impose oxidative stress in the DL cells. This was consistent with the enhanced
      p53 level, decline in Bcl2/Bax ratio and activation of caspase 9 in those DL
      cells. The findings suggest that Ru(II)-CNEB is able to activate oxidative stress
      apoptosis pathway via p53 (a tumor supressor protein) mediated repression of
      iPFK2, a key glycolytic regulator, in the DL cells in vivo.

PMID- 25576834
TI  - Estimation of the Arctic aerosols from local and long-range transport using
      relationships between 210Pb and 212Pb atmospheric activity concentrations.
AB  - In this study, the aerosol activity concentrations of (210)Pb at 28 Canadian
      radiological monitoring stations from 2009 to 2013 were analyzed. The results
      show that the ratio of (210)Pb winter average concentration to summer average
      concentration increases with increasing latitude. This could be used to evaluate
      the transport of pollutants to the Arctic region such as the Arctic haze from
      Eurasia through long-range atmospheric transport during winter. Based on 12 years
      of monitoring results from the Yellowknife station that includes both (210)Pb and
      (212)Pb concentrations, the study confirms that the seasonal distribution of
      (210)Pb to (212)Pb activity concentration ratios has a significant peak in winter
      and a relatively low value in summer, which can be used as an indicator of the
      air mass flow to the Arctic. The period dominated by long-range aerosol transport
      and Arctic haze was estimated by fitting a Gaussian distribution function to the
      peak values of this ratio in winter. A peak width parameter of full width at half
      maximum (FWHM) allows a year by year estimate of the period of influence by long
      range transport of aerosols, and this varied between 67 and 88 days in this
      study. The fitted Gaussian peak also shows that the season of the continental
      influenced air mass in Yellowknife usually starts in mid-to-late November and
      ends in mid-to-late April. Thus, the (210)Pb to (212)Pb ratio distributions may
      enable the determination of periods dominated by long-range aerosol transport and
      the scale of the Arctic haze at different latitudes. 

PMID- 25576835
TI  - Ethnic density and obesity: evidence from fixed-effects models.
AB  - We use data from the 1980 to 2004 waves of the National Longitudinal Survey of
      Youth, 1979 Cohort to examine the association between the ethnic density of
      metropolitan areas and obesity among U.S. blacks and Latinos. Although minority
      groups' obesity rates tend to be higher in metropolitan areas containing many co
      ethnics, controlling for other areal characteristics and unobserved time-constant
      confounders via fixed-effects models dramatically alters this association. In the
      fixed-effects models, higher levels of co-ethnic density are inversely associated
      with black males' obesity risk and unrelated to the obesity risk of black
      females, Latinas, and Latino males. For most groups, marrying and having children
      increases the risk of obesity. 

PMID- 25576836
TI  - Dreaming of toilets: using photovoice to explore knowledge, attitudes and
      practices around water-health linkages in rural Kenya.
AB  - As part of a knowledge, attitudes, practices and empowerment (KAPE) project
      implemented by the United Nations University Institute for Water, Environment and
      Health (UNU-INWEH) in the Lake Victoria Basin, this paper reports findings from a
      photovoice study with women in Usoma, a lakeshore community in Western Kenya.
      Drawing on ecosocial and political ecology theory, findings reveal that access to
      water, perceptions and practices were shaped by ecological and broader structural
      factors. Further, collective actions to improve access were constrained by
      institutional and economic structures, thus (re)enforcing inequalities. 

PMID- 25576837
TI  - Mobilizing Drug Consumption Rooms: inter-place networks and harm reduction drug
      policy.
AB  - This article discusses the learning and politics involved in spreading Drug
      Consumption Rooms (DCRs) globally. DCRs are health facilities, operating under a
      harm reduction philosophy, where people consume illicit drugs in a supervised
      setting. Approximately 90 are located in almost 60 cities in 11 countries. They
      are intensely local attempts to improve the lives of specific populations and
      urban neighborhoods. DCRs are also global models that travel. This article
      examines the relationship between DCRs as facilities that are fixed in place and
      DCRs as globally-mobilized models of drug policy and public health practice.
      Drawing on research from seven countries, we apply concepts from the policy
      mobilities literature to analyze the travels of the DCR model and the political
      strategies involved in the siting of these public health service facilities. We
      detail the networked mobilization of the DCR model from Europe to Canada and
      Australia, the learning among facilities, the strategies used to mold the DCR
      model to local contexts, and the role of DCR staff in promoting continued
      proliferation of DCRs. We conclude by identifying some immobilities of DCRs to
      identify questions about practices, principles and future directions of harm
      reduction. 

PMID- 25576838
TI  - Developmental patterns of emission of scent compounds and related gene expression
      in roses of the cultivar Rosa x hybrida cv. 'Yves Piaget'.
AB  - 2-Phenylethanol (2PE) and 3,5-dimethoxytoluene (DMT) are characteristic scent
      compounds in specific roses such as Rosa x hybrida cv. 'Yves Piaget'. We analyzed
      the endogenous concentrations and emission of 2PE and DMT during the unfurling
      process in different floral organs, as well as changes in transcript levels of
      the two key genes, PAR and OOMT2. The emission of both 2PE and DMT increased
      during floral development to reach peaks at the fully unfurled stage. The
      relative transcripts of PAR and OOMT2 also increased during floral development.
      Whereas the maximum for OOMT2 was found at the fully unfurled stage (stage 4),
      similar expression levels of PAR were detected at stage 4 and the senescence
      stage (stage 6). The results demonstrate a positive correlation between the
      expression levels of PAR and OOMT2 and the emission of 2PE and DMT. In addition,
      endogenous volatiles and relative transcripts showed tissue- and development
      specific patterns. 

PMID- 25576839
TI  - Early response of wheat seminal roots growing under copper excess.
AB  - Growth reduction caused by copper excess during plant photoautotrophic metabolism
      has been widely investigated, but information regarding early responses of root
      apical meristem (RAM) to toxic concentrations of this metal at the initial
      heterotrophic stage is certainly scarce. We analysed some determinants of seminal
      root growth in developing wheat seedlings germinated in the presence of 1, 5 and
      10 MUM CuCl2, focussing on oxidative damage to cell membrane and to proteins, and
      investigated the expression patterns of some genes relevant to cell cycle
      progression and cell expansion. The proliferation zone of the RAM was shorter
      under 5 and 10 MUM CuCl2. Cyclin D and CDKA levels remained unchanged in the root
      apexes of wheat seedlings grown under these Cu(2+) concentrations, but more
      carbonylated levels of both proteins and less ubiquitinated-cyclin D was detected
      under 10 MUM CuCl2. Increased levels of ROS were revealed by fluorescent probes
      at this Cu(2+) dose, and severe cell membrane damage took place at 5 and 10 MUM
      CuCl2. Several genes related to retinoblastome phosphorylation and therefore
      involved in the transition from G1 to S cell cycle stage were found to be
      downregulated at 10 MUM CuCl2, while most expansin genes here analysed were
      upregulated, even at a non-toxic concentration of 1 MUM. These results together
      with previous findings suggest that a "common" signal which involves oxidative
      posttranslational modifications of specific cell cycle proteins may be necessary
      to induce root growth arrest under Cd(2+) and Cu(2+) stress.

PMID- 25576840
TI  - High-temperature effect on genes engaged in DNA methylation and affected by DNA
      methylation in Arabidopsis.
AB  - Along with its essential role in the maintenance of genome integrity, DNA
      methylation takes part in regulation of genes which are important for plant
      development and stress response. In plants, DNA methylation process can be
      directed by small RNAs in process known as RNA-directed DNA methylation (RdDM)
      involving two plant-specific RNA polymerases - PolIV and PolV. The aim of the
      present study was to investigate the effect of heat stress on the expression of
      genes encoding key players in DNA methylation - DNA methyltransferase (MET1,
      CMT3, and DRM2), the largest subunits of PoIIV and PolV (NRPD1 and NRPE1
      respectively) and the DNA demethylase ROS1. We also examined the high-temperature
      effect on two protein-coding genes - At3g50770 and At5g43260 whose promoters
      contain transposon insertions and are affected by DNA-methylation, as well as on
      the AtSN1, a SINE-like retrotransposon. To assess the involvement of PolIV and
      PolV in heat stress response, the promoter methylation status and transcript
      levels of these genes were compared between wild type and double mutant lacking
      NRPD1 and NRPE1. The results demonstrate coordinated up-regulation of the DRM2,
      NRPD1 and NRPE1 in response to high temperature and suggest that PolIV and/or
      PolV might be required for the induction of DRM2 expression under heat stress.
      The ROS1 expression was confirmed to be suppressed in the mutant lacking active
      PolIV and PolV that might be a consequence of abolished DNA methylation. The
      increased expression of At3g50770 in response to elevated temperature correlated
      with reduced promoter DNA methylation, while the stress response of At5g43260 did
      not show inverse correlation between promoter methylation and gene expression.
      Our results also imply that PolIV and/or PolV could regulate gene expression
      under stress conditions not only through RdDM but also by acting in other
      regulatory processes. 

PMID- 25576841
TI  - A key to dissect the triad of insomnia, chronic pain, and depression.

PMID- 25576842
TI  - The Acanthamoeba shikimate pathway has a unique molecular arrangement and is
      essential for aromatic amino acid biosynthesis.
AB  - The shikimate pathway is the only known biosynthetic route for de novo synthesis
      of aromatic compounds. It is described as an ancient eukaryotic innovation that
      has been retained in a subset of eukaryotes, replaced in plants through the
      acquisition of the chloroplast, but lost in many including humans. Herein, we
      demonstrate that Acanthamoeba castellanii possesses the shikimate pathway by
      biochemical and a combination of bioinformatics and molecular biological methods.
      The growth of A. castellanii (Neff strain and a recently isolated clinical
      specimen, both T4 genotypes) is inhibited by glyphosate [N-(phosphonomethyl)
      glycine], an inhibitor of EPSP synthase and the addition of phenylalanine and
      tryptophan, which are dependent on the shikimate pathway, rescued A. castellanii
      from glyphosate indicating that glyphosate was specific in action. A. castellanii
      has a novel complement of shikimate pathway enzymes including unique gene
      fusions, two Type I and one Type II DAHP synthases (for which their likely
      sensitivities to feedback inhibition by phenylalanine, tyrosine and tryptophan
      has been modelled) and a canonical chorismate synthase. The shikimate pathway in
      A. castellanii therefore has a novel molecular arrangement, is required for amino
      acid biosynthesis and represents an attractive target for antimicrobials. 

PMID- 25576843
TI  - Randomness in the evolution of cooperation.
AB  - Tag-based ethnocentric cooperation is a highly robust behavior which can evolve
      and prevail under a wide variety of conditions. Recent studies have demonstrated,
      however, that ethnocentrism can temporarily be suppressed by other competing
      strategies, especially in its early evolutionary stages. In a series of
      computational experiments, conducted with an agent-based evolutionary model of
      tag-mediated cooperation, we addressed the question of whether a stochastically
      established and once dominant non-ethnocentric strategy such as indiscriminate
      altruism can stably persist and permanently outweigh ethnocentrism. Our model,
      simulated on various complex network topologies, employs simple haploid genetics
      and asexual reproduction of computational agents equipped with memory and
      heritable phenotypic traits. We find that in combination with an implemented
      memory mechanism and tags, random bias acting in favor of altruists can lead to
      their long-lasting victory over all other types of strategists. The difference in
      density between altruistic and ethnocentric cooperators increases with greater
      rewiring of the underlying network, but decreases with growing population size.
      These findings suggest that randomness plays an important role in promoting non
      ethnocentric cooperation and contributes to our understanding of how other than
      adaptive mechanisms can initiate the design of novel behavioral phenotypes,
      thereby shaping surprisingly new evolutionary pathways. 

PMID- 25576844
TI  - Regulation of insulin sensitivity, insulin production, and pancreatic beta cell
      survival by angiotensin-(1-7) in a rat model of streptozotocin-induced diabetes
      mellitus.
AB  - The aim of this study is to determine the antidiabetic activity of Ang-(1-7), an
      important component of the renin-angiotensin system, in a rat model of
      streptozotocin (STZ)-induced type 2 diabetes mellitus (DM). A total of 36 male
      Wistar rats were randomly divided into 3 groups: control group fed standard
      laboratory diet, DM group fed high-fat diet and injected with STZ, and Ang-(1-7)
      group receiving injection of STZ followed by Ang-(1-7) treatment. Body weight,
      blood glucose levels, fasting serum Ang II and insulin levels, and homeostasis
      model assessment of insulin resistance (HOMA-IR) were measured. The pancreas was
      collected for histological examination and gene expression analysis. Notably, the
      Ang-(1-7) group showed a significant decrease in fasting blood glucose and serum
      Ang II levels and HOMA-IR values and increase in fasting serum insulin levels.
      Pancreatic beta cells in the control and Ang-(1-7) groups were normally
      distributed in the center of pancreatic islets with large clear nuclei. In
      contrast, pancreatic beta cells in the DM group had a marked shrinkage of the
      cytoplasm and condensation of nuclear chromatin. Ang-(1-7) treatment
      significantly facilitated insulin production by beta cells in diabetic rats. The
      DM-associated elevation of inducible nitric oxide synthase (iNOS), caspase-3,
      caspase-9, caspase-8, and Bax and reduction of Bcl-2 was significantly reversed
      by Ang-(1-7) treatment. Taken together, Ang-(1-7) protects against STZ-induced DM
      through improvement of insulin resistance, insulin secretion, and pancreatic beta
      cell survival, which is associated with reduction of iNOS expression and
      alteration of the Bcl-2 family. 

PMID- 25576846
TI  - Computational methods in metabolic engineering for strain design.
AB  - Metabolic engineering uses genetic approaches to control microbial metabolism to
      produce desired compounds. Computational tools can identify new biological routes
      to chemicals and the changes needed in host metabolism to improve chemical
      production. Recent computational efforts have focused on exploring what compounds
      can be made biologically using native, heterologous, and/or enzymes with broad
      specificity. Additionally, computational methods have been developed to suggest
      different types of genetic modifications (e.g. gene deletion/addition or up/down
      regulation), as well as suggest strategies meeting different criteria (e.g. high
      yield, high productivity, or substrate co-utilization). Strategies to improve the
      runtime performances have also been developed, which allow for more complex
      metabolic engineering strategies to be identified. Future incorporation of
      kinetic considerations will further improve strain design algorithms. 

PMID- 25576845
TI  - Computing the functional proteome: recent progress and future prospects for
      genome-scale models.
AB  - Constraint-based models enable the computation of feasible, optimal, and realized
      biological phenotypes from reaction network reconstructions and constraints on
      their operation. To date, stoichiometric reconstructions have largely focused on
      metabolism, resulting in genome-scale metabolic models (M-Models). Recent
      expansions in network content to encompass proteome synthesis have resulted in
      models of metabolism and protein expression (ME-Models). ME-Models advance the
      predictions possible with constraint-based models from network flux states to the
      spatially resolved molecular composition of a cell. Specifically, ME-Models
      enable the prediction of transcriptome and proteome allocation and limitations,
      and basal expression states and regulatory needs. Continued expansion in
      reconstruction content and constraints will result in an increasingly refined
      representation of cellular composition and behavior. 

PMID- 25576847
TI  - Plasma arginine/ADMA ratio as a sensitive risk marker for atherosclerosis:
      Shimane CoHRE study.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA), which acts an endogenous
      inhibitor of nitric oxide synthase (NOS), is involved in the pathogenesis of
      cardiovascular disease. Arginine (Arg) may regulate vascular endothelial
      function, since Arg is the substrate of NO competing with ADMA. In our previous
      study, low Arg/ADMA ratio is an independent risk for microangiopathy-related
      cerebral damage. PURPOSE: Here, we performed a cross-sectional study to evaluate
      the association between the Arg/ADMA ratio and the maximal intima-media thickness
      (IMT) in the carotid artery. SUBJECTS AND METHODS: Participants were 785
      community-dwelling Japanese people without any severe disorders. Plasma
      concentration of Arg and ADMA in fasting blood sample was determined using HPLC.
      IMT was measured in the bilateral carotid artery by ultrasonography. RESULTS:
      Among quartiles stratified by the Arg/ADMA ratio, ANOVA showed a significant
      difference in IMT and the IMT in Q1 (the lowest quartile) was significantly
      higher than that in Q4 (the highest quartile). In multiple linear regression
      analysis, age, the male gender, lower BMI, the presence of hypertension and lower
      Arg/ADMA ratio were independently correlated with IMT, while IMT was not
      correlated with Arg or ADMA alone. In addition, the Arg/ADMA ratio was associated
      with IMT independent of age, sex, BMI and the presence of hypertension with odds
      ratio 0.21 (95%CI: 0.05-0.88) in multiple logistic regression analysis for IMT
      1.5 mm or more. CONCLUSION: Imbalance of Arg and ADMA is independently involved
      in the progression of atherosclerosis, and the Arg/ADMA ratio may be a sensitive
      marker for atherosclerosis.

PMID- 25576848
TI  - Bilirubin, platelet activation and heart disease: a missing link to
      cardiovascular protection in Gilbert's syndrome?
AB  - Gilbert's syndrome (GS) is a relatively common condition, inducing a benign, non
      hemolytic, unconjugated hyperbilirubinemia. Gilbert's Syndrome is associated with
      mutation in the Uridine Glucuronosyl Transferase 1A1 (UGT1A1) gene promoter,
      reducing UGT1A1 activity, which normally conjugates bilirubin allowing its
      elimination from the blood. Individuals with GS demonstrate mildly elevated
      plasma antioxidant capacity caused by elevated levels of unconjugated bilirubin
      (UCB), reduced thiols and glutathione. Interestingly, the development of, and
      risk of mortality from, cardiovascular disease is remarkably reduced in GS
      individuals. An explanation for this protection may be explained by bilirubin's
      ability to inhibit multiple processes that induce platelet hyper-reactivity and
      thrombosis, thus far under-appreciated in the literature. Reactive oxygen species
      are produced continuously via metabolic processes and have the potential to
      oxidatively modify proteins and lipids within cell membranes, which may encourage
      the development of thrombosis and CVDs. Oxidative stress induced platelet hyper
      reactivity significantly increases the risk of thrombosis, which can potentially
      lead to tissue infarction. Here, we discuss the possible mechanisms by which
      increased antioxidant status might influence platelet function and link this to
      cardiovascular protection in GS. In summary, this is the first article to discuss
      the possible role of bilirubin as an anti-thrombotic agent, which inhibits
      platelet activation and potentially, organ infarction, which could contribute to
      the reduced mortality rate in mildly hyperbilirbinemic individuals. 

PMID- 25576849
TI  - Statin myopathy: a problem looking for a solution.

PMID- 25576850
TI  - The effect of wild card designations and rare alleles in forensic DNA database
      searches.
AB  - Forensic DNA databases are powerful tools used for the identification of persons
      of interest in criminal investigations. Typically, they consist of two parts: (1)
      a database containing DNA profiles of known individuals and (2) a database of DNA
      profiles associated with crime scenes. The risk of adventitious or chance matches
      between crimes and innocent people increases as the number of profiles within a
      database grows and more data is shared between various forensic DNA databases,
      e.g. from different jurisdictions. The DNA profiles obtained from crime scenes
      are often partial because crime samples may be compromised in quantity or
      quality. When an individual's profile cannot be resolved from a DNA mixture,
      ambiguity is introduced. A wild card, F, may be used in place of an allele that
      has dropped out or when an ambiguous profile is resolved from a DNA mixture.
      Variant alleles that do not correspond to any marker in the allelic ladder or
      appear above or below the extent of the allelic ladder range are assigned the
      allele designation R for rare allele. R alleles are position specific with
      respect to the observed/unambiguous allele. The F and R designations are made
      when the exact genotype has not been determined. The F and R designation are
      treated as wild cards for searching, which results in increased chance of
      adventitious matches. We investigated the probability of adventitious matches
      given these two types of wild cards.

PMID- 25576851
TI  - Dihydrolipoyl dehydrogenase as a potential UVB target in skin epidermis; using an
      integrated approach of label-free quantitative proteomics and targeted metabolite
      analysis.
AB  - Photodamage is extrinsically induced by overexposure to ultraviolet (UV)
      radiation, and it increases the risk of various skin disorders. Therefore,
      discovery of novel biomarkers of photodamage is important. In this study, using
      LC-MS/MS analysis of epidermis from UVB-irradiated hairless mice, we identified
      57 proteins whose levels changed after UVB exposure, and selected 7 proteins
      related to the tricarboxylic acid (TCA) cycle through pathway analysis.
      Dihydrolipoyl dehydrogenase (DLD) was the only TCA cycle-associated protein that
      showed a decreased expression after the UVB exposure. We also performed targeted
      analysis to detect intermediates and products of the TCA cycle using GC-TOF-MS.
      Interestingly, malic acid and fumaric acid levels significantly decreased in the
      UVB-treated group. Our results demonstrate that DLD and its associated
      metabolites, malic acid and fumaric acid, may be candidate biomarkers of UVB
      induced skin photoaging. Additionally, we showed that Aloe vera, a natural skin
      moisturizer, regulated DLD, malic acid and fumaric acid levels in UVB-exposed
      epidermis. Our strategy to integrate the proteome and targeted metabolite to
      detect novel UVB targets will lead to a better understanding of skin photoaging
      and photodamage. Our study also supports that A. vera exerts significant anti
      photodamage activity via regulation of DLD, a novel UVB target, in the epidermis.
      BIOLOGICAL SIGNIFICANCE: This study is the first example of an integration of
      proteomic and metabolite analysis techniques to find new biomarker candidates for
      the regulation of the UVB-induced skin photoaging. DLD, malic acid, and fumaric
      acid can be used for development of cosmeceuticals and nutraceuticals regulating
      the change of skin metabolism induced by the UVB overexposure. Moreover, this is
      also the first attempt to investigate the role of the TCA cycle in photodamaged
      epidermis. Our integration of the proteomic and targeted metabolite analyses will
      lead to a better understanding of the unidentified photobiological results from
      UVB-irradiated models and can elicit new diagnostic and treatment strategies
      based on altered metabolism.

PMID- 25576853
TI  - Proteomic characterization and comparison of mammalian milk fat globule proteomes
      by iTRAQ analysis.
AB  - Milk fat globule membrane (MFGM) proteins are known to be involved in many
      biological functions; however, their components and inter-species complexity have
      not yet been completely elucidated. We investigated the protein composition of
      the MFGM-enriched fraction from Holstein, Jersey, yak, buffalo, goat, camel,
      horse, and human. Extracted proteins from the MFGM-enriched fractions were
      identified and quantified by an iTRAQ proteomic approach. We identified 520
      protein species categorized as biological processes, cellular components and
      molecular function according to their annotation. Cellular process, localization,
      transport, signal transduction, and response to stimulus were the most common
      biological processes; binding and catalytic activities were the most prevalent
      molecular functions. Pathway analysis revealed several pathways, including
      glycolysis/gluconeogenesis, peroxisome proliferator-activated receptor signaling,
      and fatty acid biosynthesis. Quantified MFGM-enriched proteins were subjected to
      discriminative proteomic profiling by principal component analysis and a
      hierarchical clustering method, and then organized into four major clusters: (1)
      Holstein, Jersey, and yak milk; (2) buffalo and goat milk; (3) Holstein, Jersey,
      buffalo, yak, and goat milk; and (4) camel, horse, and human milk. These novel
      quantitative data provide insight into the protein composition of the MFGM and
      their potential physiological functions, and highlight the significant
      differences in the MFGM fractions among mammalian species. BIOLOGICAL
      SIGNIFICANCE: Milk fat globule membrane (MFGM) proteins have exhibited a
      relatively larger diversity than other milk fractions, and implicated health
      beneficial effects. Proteomic analysis of MFGM protein was mainly focused on
      human, bovine and goat in previous studies. Recently, there is an increasing
      demand for natural milk from minor dairy animals. Differences in protein
      components were not yet elucidated that required the integration of this
      information across multiple species. Thus, iTRAQ analysis of the proteins in MFGM
      fractions from Holstein, Jersey, yak, buffalo, goat, camel, horse, and human was
      performed in this study. A total of 520 proteins were identified and quantified
      in the MFGM fractions. The results were contributed to a comprehensive overview
      and discriminative profiling of the MFGM proteome across species.

PMID- 25576852
TI  - Sexual differences in the sialomes of the zebra tick, Rhipicephalus pulchellus.
AB  - Ticks rely exclusively on vertebrate blood for their survival. During feeding
      ticks inject into their hosts a sophisticated salivary potion that overcomes host
      hemostasis and adverse inflammatory responses. These mediators may also enhance
      pathogen transmission. Knowledge of the tick salivary protein repertoire may lead
      to vaccine targets to disrupt feeding and/or parasite transmission as well as to
      the discovery of novel pharmacological agents. Male saliva may also assist
      reproduction because males use their mouthparts to lubricate and introduce their
      spermatophores into the females' genital pore. The analyses of the sialomes of
      male and female ticks independently allow us to understand the strategy used by
      each gender to feed successfully. We sequenced cDNA libraries from pools of
      salivary glands from adult male and female Rhipicephalus pulchellus feeding at
      different time points, using the Illumina HiSeq protocol. De novo assembly of a
      total of 241,229,128 paired-end reads lead to extraction of 50,460 coding
      sequences (CDS), 11,277 of which had more than 75% coverage to known transcripts,
      or represented novel sequences, and were submitted to GenBank. Additionally, we
      generated the proteome, from the salivary gland extracts of male and female R.
      pulchellus, yielding a total of 454 and 2063 proteins respectively which were
      identified by one or more peptides with at least 95% confidence. The data set is
      presented as an annotated hyperlinked Excel spreadsheet, describing 121 putative
      secreted protein families. Female and male specific transcripts were identified.
      BIOLOGICAL SIGNIFICANCE: This annotated R. pulchellus database represents a
      mining field for future experiments involving the resolution of time-dependent
      transcript expression in this tick species, as well as to define novel vaccine
      targets and discover novel pharmaceuticals. Gender specific proteins may
      represent different repertoires of pharmacological reagents to assist feeding by
      each sex, and in males may represent proteins that assist reproduction similarly
      to seminal proteins in other animals.

PMID- 25576854
TI  - A signature for immune response correlates with HCV treatment outcome in
      Caucasian subjects.
AB  - Broad proteomic profiling was performed on serum samples of phase 2 studies
      (PROVE1, PROVE2, and PROVE3) of the direct-acting antiviral drug telaprevir in
      combination with peg-interferon and ribavirin in subjects with HCV. Using only
      profiling data from subjects treated with peg-interferon and ribavirin, a
      signature composed of pretreatment levels of 13 components was identified that
      correlated well (R(2)=0.68) with subjects' underlying immune response as measured
      by week 4 viral decline and was highly predictive of sustained virologic response
      in non-African American subjects (AUC=0.99). The signature was validated by
      predicting in an independent cohort of non-African American subjects treated with
      telaprevir, peg-interferon and ribavirin (AUC=0.854). Samples from extreme
      responders were over-represented in these analyses. Proteins identified as
      differentially-expressed between responders and non-responders to HCV treatment
      were quantified using multiple reaction monitoring in samples from all Caucasian
      subjects in the peg-interferon and ribavirin arms of PROVE1 and PROVE2, revealing
      15 proteins that were significantly differentially expressed between treatment
      responders and non-responders. Seven of the proteins are part of focal adhesions
      or other macromolecular assemblies that form structural links between integrins
      and the actin cytoskeleton and are involved in antiviral response. BIOLOGICAL
      SIGNIFICANCE: HCV is a significant health problem. We describe a novel approach
      for identifying markers that predicts HCV treatment response different treatment
      regimens and use this approach to identify a novel HCV treatment response
      signature. The signature has potential to guide optimization of HCV treatment
      regimens.

PMID- 25576855
TI  - High bone mass in adult mice with diet-induced obesity results from a combination
      of initial increase in bone mass followed by attenuation in bone formation;
      implications for high bone mass and decreased bone quality in obesity.
AB  - Obesity is generally recognized as a condition which positively influences bone
      mass and bone mineral density (BMD). Positive effect of high body mass index
      (BMI) on bone has been recognized as a result of increased mechanical loading
      exerted on the skeleton. However, epidemiologic studies indicate that obesity is
      associated with increased incidence of fractures. The results presented here
      offer a new perspective regarding the mechanisms which may be responsible for the
      increase of bone mass and concurrent decrease in bone quality. Two groups of 12
      week old C57BL/6 males were fed either high fat diet (HFD) or regular diet (RD)
      for 11 weeks. Metabolic profile, bone parameters and gene expression were
      assessed in these groups at the end of the experiment. Additionally, bone status
      was evaluated in a third group of 12 week old animals corresponding to animals at
      the start of the feeding period. Administration of HFD resulted in development of
      a diet-induced obesity (DIO), glucose intolerance, alteration in energy
      metabolism, and impairment in WAT function, as compared to the age-matched
      control animals fed RD. The expression of adiponectin, FABP4/aP2, DIO2 and FoxC2
      were decreased in WAT of DIO animals, as well as transcript levels for IGFBP2,
      the cytokine regulating both energy metabolism and bone mass. At the end of
      experiment, DIO mice had higher bone mass than both control groups on RD, however
      they had decreased bone formation, as assessed by calcein labeling, and increased
      marrow adipocyte content. This study suggests that the bone mass acquired in
      obesity is a result of a two-phase process. First phase would consist of either
      beneficial effect of fat expansion to increase bone mass by increased mechanical
      loading and/or increased production of bone anabolic adipokines and/or
      nutritional effect of fatty acids. This is followed by a second phase
      characterized by decreased bone formation and bone turnover resulting from
      development of metabolic impairment. 

PMID- 25576856
TI  - Fenofibrate (PPARalpha agonist) induces beige cell formation in subcutaneous
      white adipose tissue from diet-induced male obese mice.
AB  - Browning is characterized by the formation of beige/brite fat depots in
      subcutaneous white adipose tissue (sWAT). This study aimed to examine whether the
      chronic activation of PPARalpha by fenofibrate could induce beige cell depots in
      the sWAT of diet-induced obese mice. High-fat fed animals presented overweight,
      insulin resistance and displayed adverse sWAT remodeling. Fenofibrate
      significantly attenuated these parameters. Treated groups demonstrated active UCP
      1 beige cell clusters within sWAT, confirmed through higher gene expression of
      PPARalpha, PPARbeta, PGC1alpha, BMP8B, UCP-1, PRDM16 and irisin in treated
      groups. PPARalpha activation seems to be pivotal to trigger browning through
      irisin induction and UCP-1 transcription, indicating that fenofibrate increased
      the expression of genes typical of brown adipose tissue (BAT) in the sWAT,
      characterizing the formation of beige cells. These findings put forward a
      possible role of PPARalpha as a promising therapeutic for metabolic diseases via
      beige cell induction. 

PMID- 25576857
TI  - Vitamin D supplementation during short-term caloric restriction in healthy
      overweight/obese older women: Effect on glycemic indices and serum osteocalcin
      levels.
AB  - The effect of vitamin D supplementation and caloric restriction (CR) on glycemic
      indices and osteocalcin (OC) is not clear. In this randomized controlled double
      blind trial, we examined whether vitamin D3 supplementation at 2500 IU/d (D) or
      placebo has differential effects on markers of insulin sensitivity and bone
      turnover in overweight/obese postmenopausal women during 6 weeks of caloric
      restriction (weight loss; WL, n = 39) compared to weight maintenance (WM, n =
      37). Seventy-six women (57 +/- 6 years) completed this study and the WL groups
      lost 4 +/- 1% of body weight. Baseline serum 25-hydroxyvitamin D (25OHD) was 24.8
      +/- 5.6 ng/mL at baseline; the rise was greatest in WL-D group (p < 0.05). There
      was an interaction between vitamin D intake and weight on serum OC, insulin,
      glucose and markers of insulin sensitivity (p < 0.05). The change in OC was
      explained by changes in serum 25OHD and insulin (model R(2) = 25.6%). Overall,
      vitamin D supplementation and CR influence serum osteocalcin levels and modestly
      favor improvements in insulin sensitivity.

PMID- 25576858
TI  - Kinetic characterization of human thyroperoxidase. Normal and pathological enzyme
      expression in Baculovirus system: a molecular model of functional expression.
AB  - BACKGROUND: Human thyroperoxidase (hTPO) is a membrane-bound glycoprotein located
      at the apical membrane of the thyroid follicular cells which catalyzes iodide
      oxidation and organification in the thyroglobulin (TG) tyrosine residues, leading
      to the thyroid hormone synthesis by coupling of iodotyrosine residues. Mutations
      in hTPO gene are the main cause of iodine organification defects (IOD) in
      infants. METHODS: We investigated the functional impact of hTPO gene missense
      mutations previously identified in our laboratory (p.C808R, p.G387R and p.P499L).
      In order to obtain the whole wild-type (WT) coding sequence of hTPO, sequential
      cloning strategy in pGEMT vector was carried out. Then, site-directed mutagenesis
      was performed. WT and mutant hTPOs were cloned into the pAcGP67B transfer vector
      and the recombinant proteins were expressed in Baculovirus System, purified and
      characterized by SDS-PAGE and Western blot. Moreover, we report for the first
      time the kinetic constants of hTPO, of both WT and mutant enzymes. RESULTS: The
      functional evaluation of the recombinant hTPOs showed decreased activity in the
      three mutants with respect to WT. Regarding to the affinity for the substrate,
      the mutants showed higher Km values with respect to the WT. Additionally, the
      three mutants showed lower reaction efficiencies (Vmax/Km) with respect to WT
      hTPO. CONCLUSIONS: We optimize the expression and purification of recombinant
      hTPOs using the Baculovirus System and we report for the first time the kinetic
      characterization of hTPOs.

PMID- 25576859
TI  - Guanylate cyclase C agonists: emerging gastrointestinal therapies and actions.

PMID- 25576860
TI  - Hepatitis C treatment: the data flood goes on-an update from the liver meeting
      2014.

PMID- 25576861
TI  - Optimization of the tissue source, malignancy, and initial substrate of tumor
      cell-derived matrices to increase cancer cell chemoresistance against 5
      fluorouracil.
AB  - The low chemoresistance of in vitro cancer cells inhibits the development of new
      anti-cancer drugs. Thus, development of a new in vitro culture system is required
      to increase the chemoresistance of in vitro cancer cells. Tumor cell-derived
      matrices have been reported to increase the chemoresistance of in vitro cancer
      cells. However, it remains unclear how tissue sources and the malignancy of cells
      used for the preparation of matrices affect the chemoresistance of tumor cell
      derived matrices. Moreover, it remains unclear how the initial substrates used
      for the preparation of matrices affect the chemoresistance. In this study, we
      compared the effects of tissue sources and the malignancy of tumor cells, as well
      as the effect of the initial substrates on chemoresistance against 5-fluorouracil
      (5-FU). The chemoresistance of breast and colon cancer cells against 5-FU
      increased on matrices prepared with cells derived from the corresponding original
      tissues with higher malignancy. Moreover, the chemoresistance against 5-FU was
      altered on matrices prepared using different initial substrates that exhibited
      different characteristics of protein adsorption. Taken together, these results
      indicated that the appropriate selection of tissue sources, malignancy of tumor
      cells, and initial substrates used for matrix preparation is important for the
      preparation of tumor cell-derived matrices for chemoresistance assays.

PMID- 25576862
TI  - 3D-fibroblast tissues constructed by a cell-coat technology enhance tight
      junction formation of human colon epithelial cells.
AB  - Caco-2, human colon carcinoma cell line, has been widely used as a model system
      for intestinal epithelial permeability because Caco-2 cells express tight
      junctions, microvilli, and a number of enzymes and transporters characteristic of
      enterocytes. However, the functional differentiation and polarization of Caco-2
      cells to express sufficient tight-junctions (a barrier) usually takes over 21
      days in culture. This may be due to the cell culture environment, for example
      inflammation induced by plastic petri dishes. Three-dimensional (3D) sufficient
      cell microenvironments similar to in vivo natural conditions (proteins and
      cells), will promote rapid differentiation and higher functional expression of
      tight junctions. Herein we report for the first time an enhancement in tight
      junction formation by 3D-cultures of Caco-2 cells on monolayered (1L) and eight
      layered (8L) normal human dermal fibroblasts (NHDF). Trans epithelial electric
      resistance (TEER) of Caco-2 cells was enhanced in the 3D-cultures, especially 8L
      NHDF tissues, depending on culture times and only 10 days was enough to reach the
      same TEER value of Caco-2 monolayers after a 21 day incubation. Relative mRNA
      expression of tight-junction proteins of Caco-2 cells on 3D-cultures showed
      higher values than those in monolayer structures. Transporter gene expression
      patterns of Caco-2 cells on 3D-constructs were almost the same as those of Caco-2
      monolayers, suggesting that there was no effect of 3D-cultures on transporter
      protein expression. The expression correlation between carboxylesterase 1 and 2
      in 3D-cultures represented similar trends with human small intestines. The
      results of this study clearly represent a valuable application of 3D-Caco-2
      tissues for pharmaceutical applications.

PMID- 25576863
TI  - WITHDRAWN: IRE1alpha-TRAF2-ASK1 complex-mediated endoplasmic reticulum stress and
      mitochondrial dysfunction contribute to CXC195-induced apoptosis in human bladder
      carcinoma T24 cells.
AB  - This article has been withdrawn at the request of the author. The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 25576864
TI  - A rare mutation in MYH7 gene occurs with overlapping phenotype.
AB  - Mutations in the beta-myosin heavy chain gene (MYH7) cause different muscle
      disorders. The specific molecular pathobiological processes that cause these
      different phenotypes remains unexplained. We describe three members of a family
      with an autosomal dominant mutation in the distal rod of MYH7 [c.5401G> A
      (p.Glu1801Lys)] displaying a complex phenotype characterized by Laing Distal
      Myopathy like phenotype, left ventricular non compaction cardiomyopathy and Fiber
      Type Disproportion picture at muscle biopsy. We suggest that this overlapping
      presentation confirm the phenotypic variability of MYH7 myopathy and may be
      helpful to improve the genotype phenotype correlation. 

PMID- 25576865
TI  - Comparative study on the inhibition of plasmin and delta-plasmin via benzamidine
      derivatives.
AB  - The potent fibrinolytic enzyme, plasmin has numerous clinical applications for
      recannulizing vessels obstructed by thrombus. Despite its diminutive size, 91
      kDa, success in the recombinant expression of this serine protease has been
      limited. For this reason, a truncated non-glycosylated plasmin variant was
      developed capable of being expressed and purified from E. coli. This mutated
      plasmin, known as delta-plasmin, eliminates four of the five kringle domains
      present on native plasmin, retaining only kringle 1 fused directly to the
      unmodified catalytic domain of plasmin. This study demonstrates that delta
      plasmin exhibits similar kinetic characteristics to full length plasmin despite
      its heavily mutated form; KM = 268.78 +/- 19.12, 324.90 +/- 8.43 MUM and Kcat =
      770.48 +/- 41.73, 778.21 +/- 1.51 1/min for plasmin and delta-plasmin,
      respectively. A comparative analysis was also carried out to investigate the
      inhibitory effects of a range of benzamidine based small molecule inhibitors:
      benzamidine, p-aminobenzamidine, 4-carboxybenzamidine, 4-aminomethyl benzamidine,
      and pentamidine. All of the small molecule inhibitors, with the exception of
      unmodified benzamidine, demonstrated comparable competitive inhibition constants
      (Ki) for both plasmin and delta-plasmin ranging from Ki < 4 MUM for pentamidine
      to Ki > 1000 MUM in the case of aminomethyl benzamidine. This result further
      supports that delta-plasmin retains much of the same functionality as native
      plasmin despite its greatly reduced size and complexity. This study serves the
      purpose of demonstrating the tunable inhibition of plasmin and delta-plasmin with
      potential applications for the improved clinical delivery of delta-plasmin to
      treat various thrombi.

PMID- 25576866
TI  - APOBEC3A and 3C decrease human papillomavirus 16 pseudovirion infectivity.
AB  - Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)
      proteins are cellular DNA/RNA-editing enzymes that play pivotal roles in the
      innate immune response to viral infection. APOBEC3 (A3) proteins were reported to
      hypermutate the genome of human papillomavirus 16 (HPV16), the causative agent of
      cervical cancer. However, hypermutation did not affect viral DNA maintenance,
      leaving the exact role of A3 against HPV infection elusive. Here we examine
      whether A3 proteins affect the virion assembly using an HPV16 pseudovirion (PsV)
      production system, in which PsVs are assembled from its capsid proteins L1/L2
      encapsidating a reporter plasmid in 293FT cells. We found that co-expression of
      A3A or A3C in 293FT cells greatly reduced the infectivity of PsV. The reduced
      infectivity of PsV assembled in the presence of A3A, but not A3C, was attributed
      to the decreased copy number of the encapsidated reporter plasmid. On the other
      hand, A3C, but not A3A, efficiently bound to L1 in co-immunoprecipitation assays,
      which suggests that this physical interaction may lead to reduced infectivity of
      PsV assembled in the presence of A3C. These results provide mechanistic insights
      into A3s' inhibitory effects on the assembly phase of the HPV16 virion. 

PMID- 25576867
TI  - Active calpain in phagocytically competent human neutrophils: electroinjection of
      fluorogenic calpain substrate.
AB  - Calpain has been implicated in the apparent expansion of neutrophil plasma
      membrane that accompanies cell spreading and phagocytosis. In order to test this
      hypothesis, an internally quenched fluorescent peptide substrate of calpain-1
      which increased in fluorescence on cleavage, was micro-electroinjected into
      neutrophils. The fluorescence intensity increased in a significant number of
      neutrophils, including those which appeared to be in a morphologically resting
      (spherical) state. In order to test whether calpain was activated by an elevation
      of cytosolic Ca(2+) during the injection, Ca(2+) chelators were added to the
      injectate and cytosolic free Ca(2+) in the receiving neutrophil was
      simultaneously monitored. It was shown that this approach could be used without
      raising Ca(2+) within the injected cell. Despite this, approximately 75% of
      individual neutrophils had calpain activity which consumed the substrate within
      approx. 100 s. It was found that all neutrophils had elevated calpain activity
      were phagocytically competent; whereas neutrophils with low or undetectable
      calpain activity failed to undergo phagocytosis. This association was consistent
      with the hypothesis that calpain activity within neutrophils was necessary for
      them to undergo efficient phagocytosis.

PMID- 25576868
TI  - Hedgehog signaling is synergistically enhanced by nutritional deprivation and
      ligand stimulation in human fibroblasts of Gorlin syndrome.
AB  - Hedgehog signaling is a pivotal developmental pathway that comprises hedgehog,
      PTCH1, SMO, and GLI proteins. Mutations in PTCH1 are responsible for Gorlin
      syndrome, which is characterized by developmental defects and tumorigenicity.
      Although the hedgehog pathway has been investigated extensively in Drosophila and
      mice, its functional roles have not yet been determined in human cells. In order
      to elucidate the mechanism by which transduction of the hedgehog signal is
      regulated in human tissues, we employed human fibroblasts derived from three
      Gorlin syndrome patients and normal controls. We investigated GLI1 transcription,
      downstream of hedgehog signaling, to assess native signal transduction, and then
      treated fibroblasts with a recombinant human hedgehog protein with or without
      serum deprivation. We also examined the transcriptional levels of hedgehog
      related genes under these conditions. The expression of GLI1 mRNA was
      significantly higher in Gorlin syndrome-derived fibroblasts than in control
      cells. Hedgehog stimulation and nutritional deprivation synergistically enhanced
      GLI1 transcription levels, and this was blocked more efficiently by vismodegib, a
      SMO inhibitor, than by the natural compound, cyclopamine. Messenger RNA profiling
      revealed the increased expression of Wnt signaling and morphogenetic molecules in
      these fibroblasts. These results indicated that the hedgehog stimulation and
      nutritional deprivation synergistically activated the hedgehog signaling pathway
      in Gorlin syndrome fibroblasts, and this was associated with increments in the
      transcription levels of hedgehog-related genes such as those involved in Wnt
      signaling. These fibroblasts may become a significant tool for predicting the
      efficacies of hedgehog molecular-targeted therapies such as vismodegib. 

PMID- 25576869
TI  - Reactive oxygen species promote heat shock protein 90-mediated HBV capsid
      assembly.
AB  - Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS)
      production and has been associated with the development of hepatocellular
      carcinoma (HCC). ROS are also an important factor in HCC because the accumulated
      ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative
      stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of
      the defense mechanism. Hsp90 prevents cellular component from oxidative stress,
      and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known
      whether molecules regulated by oxidative stress are involved in HBV capsid
      assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly,
      which is an important step for the packing of viral particles, here, we show that
      ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid
      assembly was facilitated by ROS with Hsp90, whereas it was decreased without
      Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid
      assembly. Consistent with the result of cell-free system, ROS and buthionine
      sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation
      in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90
      during HBV capsid assembly. 

PMID- 25576870
TI  - Platelet-derived growth factor-D modulates extracellular matrix homeostasis and
      remodeling through TIMP-1 induction and attenuation of MMP-2 and MMP-9 gelatinase
      activities.
AB  - Platelet-derived growth factor-D (PDGF-D) is a more recent recognized growth
      factor involved in the regulation of several cellular processes, including cell
      proliferation, transformation, invasion, and angiogenesis by binding to and
      activating its cognate receptor PDGFR-beta. After bile duct ligation or in the
      carbon tetrachloride-induced hepatic fibrosis model, PDGF-D showed upregulation
      comparable to PDGF-B. Moreover, adenoviral PDGF-D gene transfer induced hepatic
      stellate cell proliferation and liver fibrosis. We here investigated the
      molecular mechanism of PDGF-D involvement in liver fibrogenesis. Therefore, the
      GRX mouse cell line was stimulated with PDGF-D and evaluated for fibrotic markers
      and PDGF-D signaling pathways in comparison to the other PDGF isoforms. We found
      that PDGF-D failed to enhance Col I and alpha-smooth muscle actin (alpha-SMA)
      production but has capacity to upregulate expression of the tissue inhibitor of
      metalloprotease 1 (TIMP-1) resulting in attenuation of MMP-2 and MMP-9 gelatinase
      activity as indicated by gelatinase zymography. This phenomenon was restored
      through application of a PDGF-D neutralizing antibody. Unexpectedly, PDGF-D
      incubation decreased both PDGFR-alpha and -beta in mRNA and protein levels, and
      PDGF-D phosphorylated typrosines specific for PDGFR-alpha and -beta. We conclude
      that PDGF-D intensifies fibrogenesis by interfering with the fibrolytic activity
      of the TIMP-1/MMP system and that PDGF-D signaling is mediated through both PDGF
      alpha and -beta receptors. 

PMID- 25576871
TI  - 7-Ketocholesterol induces the reduction of KCNMB1 in atherosclerotic blood
      vessels.
AB  - Hypertension is a high-risk symptom in atherosclerotic patients, and vascular
      rigidity is one of the main factors leading to hypertension. beta1-Subunit of
      BKCa channel (KCNMB1; MaxiKbeta1) has been reported as a modulator of vascular
      flexibility. To determine the relationship between atherosclerosis and KCNMB1, we
      studied some atherogenic factors affecting vascular tone. Blood of
      atherosclerotic patients shows increased concentration of 7-ketocholesterol (7K),
      which has been studied as a harmful lipid to blood vessels. Our data showed that
      KCNMB1 was significantly down-regulated in the presence of 7K, in a dose-/time
      dependent manner in vascular smooth muscle cells (VSMCs). And, the reduction of
      KCNMB1 was confirmed in cell images of 7K-stimulated VSMCs and in vessel tissue
      images of ApoE knock-out mice. To determine whether aryl hydrocarbon receptor
      (AhR) was involved in the reduction of KCNMB1 by 7K-stimulation, protein level of
      AhR was analyzed by Western blot. Our data showed that the reduction of KCNMB1
      was modulated through the AhR pathway. In conclusion, results of our study
      suggest that 7K induces the reduction of KCNMB1 through the AhR pathway. 

PMID- 25576872
TI  - Lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) is a substrate of
      cathepsin-F, a cysteine protease mutated in type-B-Kufs-disease.
AB  - The lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) has been
      identified as a receptor for enterovirus 71 uptake and mannose-6-phosphate
      independent lysosomal trafficking of the acid hydrolase beta-glucocerebrosidase.
      Here we show that LIMP-2 undergoes proteolytic cleavage mediated by lysosomal
      cysteine proteases. Heterologous expression and in vitro studies suggest that
      cathepsin-F is mainly responsible for the lysosomal processing of wild-type LIMP
      2. Furthermore, examination of purified lysosomes revealed that LIMP-2 undergoes
      proteolysis in vivo. Mutations in the gene encoding cathepsin-F (CTSF) have
      recently been associated with type-B-Kufs-disease, an adult form of neuronal
      ceroid-lipofuscinosis. In this study we show that disease-causing cathepsin-F
      mutants fail to cleave LIMP-2. Our findings provide evidence that LIMP-2
      represents an in vivo substrate of cathepsin-F with relevance for understanding
      the pathophysiology of type-B-Kufs-disease.

PMID- 25576873
TI  - Extracellular acidification activates ovarian cancer G-protein-coupled receptor 1
      and GPR4 homologs of zebra fish.
AB  - Mammalian ovarian G-protein-coupled receptor 1 (OGR1) and GPR4 are identified as
      a proton-sensing G-protein-coupled receptor coupling to multiple intracellular
      signaling pathways. In the present study, we examined whether zebra fish OGR1 and
      GPR4 homologs (zOGR1 and zGPR4) could sense protons and activate the multiple
      intracellular signaling pathways and, if so, whether the similar positions of
      histidine residue, which is critical for sensing protons in mammalian OGR and
      GPR4, also play a role to sense protons and activate the multiple signaling
      pathways in the zebra fish receptors. We found that extracellular acidic pH
      stimulated CRE-, SRE-, and NFAT-promoter activities in zOGR1 overexpressed cells
      and stimulated CRE- and SRE- but not NFAT-promoter activities in zGPR4
      overexpressed cells. The substitution of histidine residues at the 12th, 15th,
      162th, and 264th positions from the N-terminal of zOGR1 with phenylalanine
      attenuated the proton-induced SRE-promoter activities. The mutation of the
      histidine residue at the 78th but not the 84th position from the N-terminal of
      zGPR4 to phenylalanine attenuated the proton-induced SRE-promoter activities.
      These results suggest that zOGR1 and zGPR4 are also proton-sensing G-protein
      coupled receptors, and the receptor activation mechanisms may be similar to those
      of the mammalian receptors. 

PMID- 25576874
TI  - Structure and evolution of N-domains in AAA metalloproteases.
AB  - Metalloproteases of the AAA (ATPases associated with various cellular activities)
      family play a crucial role in protein quality control within the cytoplasmic
      membrane of bacteria and the inner membrane of eukaryotic organelles. These
      membrane-anchored hexameric enzymes are composed of an N-terminal domain with one
      or two transmembrane helices, a central AAA ATPase module, and a C-terminal
      Zn(2+)-dependent protease. While the latter two domains have been well studied,
      so far, little is known about the N-terminal regions. Here, in an extensive
      bioinformatic and structural analysis, we identified three major, non-homologous
      groups of N-domains in AAA metalloproteases. By far, the largest one is the FtsH
      like group of bacteria and eukaryotic organelles. The other two groups are
      specific to Yme1: one found in plants, fungi, and basal metazoans and the other
      one found exclusively in animals. Using NMR and crystallography, we determined
      the subunit structure and hexameric assembly of Escherichia coli FtsH-N,
      exhibiting an unusual alpha+beta fold, and the conserved part of fungal Yme1-N
      from Saccharomyces cerevisiae, revealing a tetratricopeptide repeat fold. Our
      bioinformatic analysis showed that, uniquely among these proteins, the N-domain
      of Yme1 from the cnidarian Hydra vulgaris contains both the tetratricopeptide
      repeat region seen in basal metazoans and a region of homology to the N-domains
      of animals. Thus, it is a modern-day representative of an intermediate in the
      evolution of animal Yme1 from basal eukaryotic precursors. 

PMID- 25576875
TI  - The use of a frailty index to predict adverse health outcomes (falls, fractures,
      hospitalization, medication use, comorbid conditions) in people with intellectual
      disabilities.
AB  - Frailty in older people can be seen as the increased likelihood of future
      negative health outcomes. Lifelong disabilities in people with intellectual
      disabilities (ID) may not only influence their frailty status but also the
      consequences. Here, we report the relation between frailty and adverse health
      outcomes in older people with ID (50 years and over). In a prospective population
      based study, frailty was measured at baseline with a frailty index in 982 older
      adults with ID (>=50 yr). Information on negative health outcomes (falls,
      fractures, hospitalization, increased medication use, and comorbid conditions)
      was collected at baseline and after a three-year follow-up period. Odds ratios or
      regression coefficients for negative health outcomes were estimated with the
      frailty index, adjusted for gender, age, level of ID, Down syndrome and baseline
      adverse health condition. The frailty index was related to an increased risk of
      higher medication use and several comorbid conditions, but not to falls,
      fractures and hospitalization. Frailty at baseline was related to negative health
      outcomes three years later in older people with ID, but to a lesser extent than
      found in the general population. 

PMID- 25576876
TI  - Kinesthetic deficit in children with developmental coordination disorder.
AB  - The aim of this study was to measure and compare kinesthetic sensitivity in
      children with developmental coordination disorder (DCD) and typically developing
      (TD) children between 6 and 11 years old. 30 children with DCD aged 6 to 11 years
      (5 in each age group) and 30 TD children participated in the study. Participants
      placed their forearms on a passive motion apparatus which extended the elbow
      joint at constant velocities between 0.15 and 1.35 degrees s(-1). Participants
      were required to concentrate on detection of passive arm motion and press a
      trigger held in their left hand once they sensed it. The detection time was
      measured for each trial. The DCD group was significantly less sensitive in
      detection of passive motion than TD children. Further analysis of individual age
      groups revealed that kinesthetic sensitivity was worse in DCD than TD children
      for age groups beyond six years of age. Our findings suggested that individual
      with DCD lag behind their TD counterparts in kinesthetic sensitivity. Between the
      ages of 7 and 11 years the difference between groups is quantifiable and
      significant with 11 year old children with DCD performing similar to 7 year old
      TD children. 

PMID- 25576877
TI  - Visuospatial working memory underlies choice-impulsivity in boys with attention
      deficit/hyperactivity disorder.
AB  - The present study examined the directional relationship between choice
      impulsivity and separate indices of phonological and visuospatial working memory
      performance in boys (aged 8-12 years) with (n=16) and without ADHD (n=19).
      Results indicated that high ratings of overall ADHD, inattention, and
      hyperactivity were significantly associated with increased impulsivity and poorer
      phonological and visuospatial working memory performance. Further, results from
      bias-corrected bootstrapped mediation analyses revealed a significant indirect
      effect of visuospatial working memory performance, through choice-impulsivity, on
      overall ADHD, inattention, and hyperactivity/impulsivity. Collectively, the
      findings suggest that deficits of visuospatial working memory underlie choice
      impulsivity, which in turn contributes to the ADHD phenotype. Moreover, these
      findings are consistent with a growing body of literature that identifies working
      memory as a central neurocognitive deficit of ADHD. 

PMID- 25576878
TI  - Weight gain and incident knee osteoarthritis in asymptomatic at risk patients: a
      step closer to primary prevention trials.

PMID- 25576879
TI  - OA phenotypes, rather than disease stage, drive structural progression-
      identification of structural progressors from 2 phase III randomized clinical
      studies with symptomatic knee OA.
AB  - BACKGROUND/PURPOSE: The aim of this study was to identify key characteristics of
      disease progression through investigation of the association of radiographic
      progression over two years with baseline Joint Space Width (JSW), Kellgren
      Lawrence (KL) grade, Western Ontario and McMaster Universities Arthritis Index
      (WOMAC) pain, Joint Space Narrowing (JSN), and BMI. METHODS: Data from 2206
      subjects (4390 knees) were combined for this post-hoc analysis of two randomized,
      double-blind, multi-center, placebo-controlled phase III trials (NCT00486434 and
      NCT00704847) that evaluated the efficacy and safety of 2-years treatment with
      oral salmon calcitonin of subjects with painful knee osteoarthritis (OA).
      RESULTS: There was a clear positive and significant correlation between KL grade
      and WOMAC pain and total WOMAC, albeit the variance in pain measures was from min
      to-max for all KL categories, emphasizing the heterogeneity of this patient
      population and pain perception. 32% of target knees did not progress, and only
      51% had changes over minimum significant change (MSC). BMI, KL-Score and WOMAC
      pain was diagnostic, but only KL-score and pain had prognostic value, albeit pain
      in a non-linear manner. CONCLUSION: These data clearly describe significant
      associations between KL grade, JSW, pain and BMI in patients with symptomatic
      knee OA. KL grade, BMI and WOMAC pain were diagnostically associated with OA
      based on JSW but only KL-score and pain in a non-linier fashion was prognostic.
      50% of patients did not progress more than MSC, highlighting the importance for
      identification of structural progressors and the phenotypes associated with
      these. These results suggest that disease phenotypes, rather than disease status,
      are responsible for disease progression.

PMID- 25576880
TI  - Pterional transsylvian-transinsular approach in three cavernomas of the left
      anterior mesiotemporal region.
AB  - OBJECTIVE: To describe the pterional transsylvian-transinsular approach for
      cavernomas of the left anterior mesiotemporal region in three patients. METHODS:
      A retrospective analysis of patients who underwent surgery for cavernous angiomas
      in the temporal lobe was performed via the left mesiotemporal lobe (MTL). The
      technique was as follows: using the pterional approach, the Sylvian fissure was
      widely opened, distally to proximally. The temporal branch of the middle cerebral
      artery was displaced medially, and once the limiting sulcus of the insula was
      located, an 8mm long corticotomy was performed, just behind the limen insulae.
      The dissection was extended through the white matter until the anterior portion
      of the temporal horn was reached. Finally, lesion resection was performed.
      RESULTS: Three patients presented with cavernomas in the anterior sector of the
      MTL and underwent the transsylvian-transinsular approach. There were no deaths in
      this series. One patient sustained a permanent postoperative deficit, a right
      homonymous quadrantanopia. CONCLUSION: The pterional transsylvian-transinsular
      approach allows for selective resection of lesions located in the anterior
      mesiotemporal region (MTR) of the dominant hemisphere, while avoiding damage to
      the lateral or basal cortex of the temporal lobe or to structures in the dominant
      hemisphere.

PMID- 25576881
TI  - Surgical resection of upper-middle clivus chordomas via a modified anterior
      transpetrous approach.
AB  - BACKGROUND: Skull base chordomas are challenging and have a high rate of
      recurrence. METHODS: A modified anterior transpetrous approach (ATPA) was
      performed in 17 upper clivus chordomas, and clinical data were retrospectively
      studied. RESULTS: All 17 cases were radically treated via the modified ATPA, and
      the total removal and subtotal removal rates were 23.5% and 76.5%, respectively.
      The primary complaints were headaches and visual disturbances. The short-term
      postoperative complications were diplopia (12 cases, 70.6%) and facial numbness
      (7 cases, 41.2%). With a mean follow up of 44.5 months, 5 cases (29.4%) presented
      with tumor recurrence, and most cases had relatively good outcomes except for 2
      patients who died because of rapid recurrence. The long-term complications were
      facial numbness (35.3%). CONCLUSIONS: The upper skull base chordomas could be
      radically removed via the modified ATPA under selected conditions, with limited
      complications and improved outcomes. The radical surgery treatment strategy was
      recommended for skull base chordomas. However, the present series included
      limited cases; therefore, post-operative follow-up, long-term outcomes and a
      larger number of cases of clivus chordomas should be observed to evaluate the
      effectiveness of the modified ATPA approach.

PMID- 25576882
TI  - Efficacy of radio frequency thermocoagulation in surgery for giant supratentorial
      meningiomas: a historical control study.
AB  - BACKGROUND: Surgery for giant meningiomas carries a high risk of bleeding and is
      time-consuming. This historical control study tests the hypothesis that the use
      of radio frequency thermocoagulation (RFT) during surgery improves outcome.
      METHODS: From November 2010 to October 2011, 20 giant vascularized meningiomas
      were surgically resected with intraoperative use of ultrasound-guided RFT prior
      to resection. The historical control group consisted of 25 patients in whom
      tumors were removed without RFT by the same surgical team. Blood loss during
      resection, changes in tumor consistency, time taken for the operation, and the
      extent of resection were compared between the two groups. RESULTS: There was less
      blood lost during resection and the duration of the operation was shorter in RFT
      assisted surgery than in the historical control group (P<0.05). Apart from the
      effect of devascularization, the tumor consistency became soft after RFT, which
      could also be beneficial. CONCLUSIONS: Satisfactory devascularization and tumor
      softening were achieved after RFT without incremental complications. RFT-assisted
      surgery for giant vascularized supratentorial meningiomas is easier and safer
      than non-RFT surgery.

PMID- 25576883
TI  - Lateral transzygomatic middle fossa approach and its extensions: surgical
      technique and 3D anatomy.
AB  - BACKGROUND: Various approaches to lesions involving the middle fossa and
      cavernous sinus (CS), with and without posterior fossa extension have been
      described. In the present study, we describe the surgical technique for the
      extradural lateral tranzygomatic middle fossa approach and its extensions,
      highlight relevant 3D anatomy. METHODS: Simulations of the lateral transzygomatic
      middle fossa approach and its extensions were performed in four silicon-injected
      formalin fixed cadaveric heads. The step-by-step description and relevant anatomy
      was documented with 3D photographs. RESULT: The lateral transzygomatic middle
      fossa approach is particularly useful for lesions involving the middle fossa with
      and without CS invasion, extending to the posterior fossa and involving the
      clinoidal region. This approach incorporates direct lateral positioning of
      patient, frontotemporal craniotomy with zygomatic arch osteotomy, extradural
      elevation of the temporal lobe, and delamination of the outer layer of the
      lateral CS wall. Extradural drilling of the sphenoid wing and anterior clinoid
      process allows entry into the CS through the superior wall and exposure of the
      clinoidal segment of the ICA. Posteriorly, drilling the petrous apex allows
      exposure of the ventral brainstem from trigeminal to facial nerve and can be
      extended to the interpeduncular fossa by division of the superior petrosal sinus.
      CONCLUSION: The present study illustrates 3D anatomical relationships of the
      lateral transzygomatic middle fossa approach with its extensions. This approach
      allows wide access to different topographic areas (clinoidal region and clinoidal
      ICA, the entire CS, and the posterior fossa from the interpeduncular fossa to the
      facial nerve) via a lateral trajectory. Precise knowledge of technique and
      anatomy is necessary to properly execute this approach.

PMID- 25576884
TI  - Frame-based stereotactic neurosurgery in children under the age of seven:
      Freiburg University's experience from 99 consecutive cases.
AB  - INTRODUCTION: Stereotactic frame-based procedures proved to be precise, safe and
      are of widespread use among adult patients. Regarding pediatric patients few data
      is available, therefore the use of the stereotactic frame remains controversial
      in this population. This motivated us to report our experience in stereotactic
      procedures in the youngest patients and review the literature concerning this
      subject. METHODS: All frame-based procedures performed in patients younger than
      seven years in the University of Freiburg during the last 10 years were
      retrospectively analyzed and discussed under the light of the current literature.
      RESULTS: The studied population was composed of 72 patients under the age of
      seven (mean 3.4+/-2.1 years-old), in whom 99 stereotactic procedures were
      performed. Brain tumor was present in 60 patients, hydrocephalus in five, cystic
      lesions in three, intracranial abscess in three and epilepsy in one patient.
      Stereotactic surgery was performed in 36 cases for brachytherapy, in 29 for
      biopsy, in 20 cases for cyst puncture, in eight for stereotactically guided
      endoscopic ventriculostomy, in five for catheter placement and in one case for
      depth electrode insertion. The overall complication rate was 5%. There were three
      cases of pin penetration through the skull, one case of frame dislocation after
      extensive cyst drainage and two skull fractures. Neurologic deficit related to
      frame fixation was observed in none of the cases. In disagreement with other
      authors, no case of pin related infection, air embolism, hematoma or CSF leak was
      observed. CONCLUSION: Frame-based stereotactic neurosurgery is a safe technique
      also in the youngest patients. Rather than the simple use of torque-limiting
      devices training and experience in the manual adjustment of the stereotactic
      frame in children have been proven to be crucial factors that contribute to
      reducing pin related complications.

PMID- 25576885
TI  - Results of endoscopic third ventriculostomy in elderly patients >=65 years of
      age.
AB  - INTRODUCTION: Endoscopic third ventriculostomy (ETV) has been accepted as the
      procedure of choice for the treatment of obstructive hydrocephalus in children
      and adults. The role and outcome of this procedure in the elderly has not been
      evaluated yet. MATERIALS AND METHODS: Over an 11-year interval we retrospectively
      analyzed data of patients, 65+ years of age, who underwent ETV in our center.
      Success of the procedure was assessed in terms of symptom relief and/or
      elimination of the need for shunting. Additionally pre- and postoperative
      ventricular volumes were estimated using Evan's index (Ei) and fronto-occipital
      horn ratio (FOR). In our analysis we compared the results of the elderly patients
      with those of the pediatric and adult age groups treated in our center. RESULTS:
      We obtained data of 16 elderly cases (11 males, 5 females), mean age 72.8 years
      (66-83 years) out of the 91 patients treated with ETV in total. The success rate
      was 75% in this age group; mean follow-up 18.4 months (2-55 months). In 10
      patients a mass lesion was the underlying cause of hydrocephalus. Mean
      ventricular size reduction was 18% and 13.5% (Ei and FOR) in the success group
      vs. 7.6% and 6.2% in the failure group. Three out of four patients who had
      shunting pre-EVT, became shunt independent post-operatively. The presence of flow
      void over the stoma was 100% correlated with success. All 7 patients with a
      primary or metastatic brain tumor were able to receive radiation therapy.
      CONCLUSION: Also in elderly, ETV is a safe and efficient procedure, with success
      rates similar to the younger population. Further research is required to set up a
      prognostic scoring system for this age group.

PMID- 25576886
TI  - Plasma fibrinogen levels in patients with benign and malignant ovarian tumors.
AB  - OBJECTIVE: Plasma fibrinogen is a key acute phase protein and known to be
      elevated in ovarian cancer. We aimed to investigate the association between
      plasma fibrinogen and malignant and benign ovarian tumors. METHODS: In a
      retrospective, single-center study, we evaluated preoperative plasma fibrinogen
      levels in 471 patients with benign and in 224 patients with malignant (borderline
      ovarian tumor [BOT]: n=36, epithelial ovarian cancer [EOC]: n=188) ovarian
      tumors. The association between preoperative plasma fibrinogen levels and clinico
      pathological parameters was investigated. A multivariate logistic regression
      model was performed to identify an independent association. RESULTS: Mean
      (standard deviation) preoperative plasma fibrinogen levels in patients with
      benign ovarian tumors, BOT, and invasive ovarian cancers were 346.7 (99.7), 372.8
      (114), and 472.6 (148.4) mg/dL, respectively (p<0.001). Within the EOC cohort,
      patients with advanced stage disease had higher plasma fibrinogen levels (485.5
      [151.3] mg/dL) than patients with early stage disease (430.9 [130.3] mg/dL;
      p=0.03). In a multivariate model plasma fibrinogen was identified to be
      independently associated with the presence of BOT and EOC. In the subgroup of
      patients <50 years, plasma fibrinogen levels remained independently associated
      with malignant ovarian tumors in CA 125 positive and negative patients.
      CONCLUSION: Plasma fibrinogen levels are independently associated with malignant
      ovarian tumors. Plasma fibrinogen levels showed an independent association with
      malignant ovarian tumors in the subgroup of patients <50 years, in whom
      differential diagnosis of ovarian tumors is particularly challenging.

PMID- 25576888
TI  - TEMPORARY REMOVAL: Celebrating the Past, Present and IDEAL Future AAGL.
AB  - The publisher regrets that this article has been temporarily removed. A
      replacement will appear as soon as possible in which the reason for the removal
      of the article will be specified, or the article will be reinstated. The full
      Elsevier Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 25576887
TI  - Mild hypoxia in vivo regulates cardioprotective SUR2A: A role for Akt and LDH.
AB  - High-altitude residents have lower mortality rates for ischaemic heart disease
      and this is ascribed to cardiac gene remodelling by chronic hypoxia. SUR2A is a
      cardioprotective ABC protein serving as a subunit of sarcolemmal ATP-sensitive
      K(+) channels. The purpose of this study was to determine whether SUR2A is
      regulated by mild hypoxia in vivo and to elucidate the underlying mechanism. Mice
      were exposed to either 21% (control) or 18% (mild hypoxia) oxygen for 24h.
      Exposure to 18% oxygen did not affect partial pressure of O(2) (PO(2)) and CO(2)
      (PCO(2)) in the blood, haematocrit or level of ATP in the heart. However, hypoxia
      increased myocardial lactate dehydrogenase (LDH) and lactate as well as NAD(+)
      without affecting total NAD. SUR2A levels were significantly increased as well as
      myocardial resistance to ischaemia-reperfusion. Exposure to 18% oxygen did not
      phosphorylate extracellular signal regulated kinases (ERK1/2) or AMP activated
      protein kinase (AMPK), but it phosphorylated protein kinase B (Akt). An inhibitor
      of phosphoinositide 3-kinases (PI3K), LY294002 (0.2mg/mouse), abolished all
      observed effects of hypoxia. LDH inhibitors, galloflavin (50 MUM) and sodium
      oxamate (80 mM) significantly decreased levels of SUR2A in heart embryonic H9c2
      cells, while inactive mutant LDH form, gly193-M-LDH increased cellular
      sensitivity towards stress induced by 2,4-dinitrophenol (10mM). Treatment of H9c2
      cells with sodium lactate (30 mM) increased intracellular lactate, but did not
      affect LDH activity or SUR2A levels. We conclude that PI3K/Akt signalling pathway
      and LDH play a crucial role in increase of cardiac SUR2A induced by in vivo
      exposure to 18% oxygen.

PMID- 25576889
TI  - Compensation among graduated fellowship in minimally invasive gynecologic surgery
      fellows.
AB  - STUDY OBJECTIVE: The Fellowship in Minimally Invasive Gynecologic Surgery (FMIGS)
      is a postresidency fellowship developed with the mission to train the next
      generation of minimally invasive gynecologic surgeons. The need for surgeons
      trained in this field has increased, yet there remains a paucity of information
      regarding the compensation of these specialized surgeons. DESIGN: A survey was
      sent via e-mail to FMIGS graduates (N = 221) using an online survey tool; it was
      sent twice more to increase the response rate between July and December 2013. The
      survey collected information on current and starting salaries and benefits as
      well as academic rank, location, practice type, and practice breadth. Comparisons
      were analyzed using multivariable linear regression models (Canadian Task Force
      Classification II-2). SETTING: E-mail-based survey. PATIENTS: Graduates of the
      FMIGS. INTERVENTIONS: A single survey sent 3 times. MEASUREMENTS AND MAIN
      RESULTS: Of 221 graduates surveyed, 164 responded (response rate = 74%). Sixty
      one percent of respondents (n = 100) were from academic institutions, and the
      remainder were from private practice (n = 64). Of all respondents, 27 (16.5%)
      reported less than 1 year of postfellowship experience and had a median starting
      salary of $216 399 (range, $106 834-$542 930). Survey respondents were on average
      3.3 years (range, 0-14) out of fellowship with a median salary of $238 198
      (range, $108 200-$993 765). Academic surgeons (average experience = 3.4 years)
      earned $208 743 (range, $106 834-$542 930) compared with private practice
      surgeons (average experience = 3.2 years) who earned $233 020 (range, $115 000
      $454 448). CONCLUSION: Salaries and compensation benefits of graduates of the
      FMIGS are varied. This information is very relevant to those attempting to hire
      or become employed as gynecologic surgical specialists.

PMID- 25576890
TI  - Decrease of colonization in the chicks' cecum and internal organs of Salmonella
      enterica serovar Pullorum by deletion of cpdB by Red system.
AB  - Salmonella enterica serovar Pullorum (S. Pullorum) is a worldwide poultry
      pathogen of considerable economic importance, particularly in those countries
      with a developing poultry industry. A variety of genes that affect S. Pullorum
      colonization in chickens had been identified. 2',3'-cyclic phosphodiesterase
      (cpdB) is the bifunctional enzyme which possess 2',3'-cyclic phosphodiesterase as
      well as 3'-nucleotidase activity. To assess the role of cpdB of S. Pullorum in
      colonization of cecum and internal organs in poultry, seven-day-old chicks were
      infected with 10(9) CFU/ml of a cpdB mutant and wild type strain. High number of
      cpdB mutant and wild type strain colonized the internal organs shortly after
      infection, but no colonization of cpdB mutant were observed from internal organs
      at day 10 post-infection, meanwhile, wild type bacteria in internal organs were
      observed at day 16 post-infection. Furthermore, the colonization of cpdB mutant
      in the cecum was seriously decreased from 6 days post-infection simultaneously
      wild type strain was increased and seriously decreased at day 8 post-infection.
      At day 12 post-infection, no cpdB mutant was observed from cecum, however high
      numbers of wild type strain were isolated at day 16 post-infection. It is
      concluded that cpdB is involved in long-term colonization of S. Pullorum in the
      chicks' cecum and internal organs. In addition, deletion of cpdB from S. Pullorum
      was not affect the morphology and growth of bacteria. 

PMID- 25576891
TI  - Circulating and excretory nitrite and nitrate: their value as measures of nitric
      oxide synthesis, bioavailability and activity is inherently limited.

PMID- 25576892
TI  - Relationships between IL-6 gene polymorphism, low BMD and periodontitis in
      postmenopausal women.
AB  - OBJECTIVE: IL-6 plays critical roles in bone resorption and the pathogenesis of
      periodontitis in both inflammation and alveolar bone loss. A negative correlation
      was observed between periodontitis and truncal bone mineral density (BMD) in
      postmenopausal women. The C allele carriers of a genetic polymorphism IL-6-572G/C
      have higher levels of serum IL-6 compared to G allele carriers. We investigated
      the possible effect of IL-6-572G/C polymorphism on the relationship between low
      BMD and periodontitis in postmenopausal women. SUBJECTS AND METHODS: A total of
      300 postmenopausal Japanese women who lived in Yokogoshi area of Niigata City,
      Japan, participated in this study. Genomic DNA was extracted from peripheral
      blood. The IL-6-572G/C genotypes were determined by the restriction fragment
      length polymorphism method. Bone mineral density (BMD) of right femoral neck and
      serum bone metabolism markers were measured. Low BMD was defined to have the
      BMD<80% of the mean for young adults. Periodontal parameters at two sites per
      tooth were measured. RESULTS: Serum osteocalcin levels were significantly lower
      in the IL-6-572G/G genotype (p=0.025). In the -572G allele non-carriers,
      percentages of PPD>=4mm sites were significantly higher in low BMD group compared
      with the healthy control group (p=0.021). Logistic regression analysis revealed
      low BMD to be associated with periodontitis (Odds ratio=1.736, p=0.027) after
      adjusted with IL-6-572G carriage, age, serum albumin level. CONCLUSIONS: IL-6
      572G/C polymorphism was not an independent risk factor of low BMD or
      periodontitis, but may affect the relationship between the two diseases in
      postmenopausal Japanese women.

PMID- 25576893
TI  - Anti-inflammatory effects of Huangqin tang extract in mice on ulcerative colitis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: HuangqinTang (HQT) is a traditional Chinese
      formula which is composed of Scutellaria baicalensis Georgi, Paeonia lactiflora
      Pall, Glycyrrhiza uralensis Fisch, and Ziziphus jujube Mill. HQT has been used in
      China for a wide range of disorders, especially in gastrointestinal inflammation
      with symptoms of nausea, vomiting, diarrhea, abdominal cramps and so on. AIM OF
      THE STUDY: To investigate the protective effects of HQT extract on 2, 4, 6
      trinitrobenzenesulfonic acid (TNBS) induced colitis in mice. MATERIALS AND
      METHODS: Different doses of HQT extract (1, 2 and 4 g/kg/day) and
      salicylazosulfapyridine (SASP, 500 mg/kg/day) were administered by gavage for 7
      days after the induction of colitis with TNBS. The effects were studied by
      macroscopic score, histological analysis, immunohistochemical study of Cyclo
      oxygenase-2 protein expression, as well as by determination of inflammation
      markers such as myeloperoxidase (MPO) and mRNA expression levels of pro
      inflammatory cytokines, including TNF-alpha, IL-1beta and IL-6. RESULTS: In TNBS
      induced group, mice body weight decreased gradually and did not recover at the
      end of the experiment, as compared with that of control group (p<0.01). Edema and
      redness were also discovered in the colons profoundly and scores representing
      inflammation were all high in this group (p<0.01). The level of colonic MPO
      activity and the tissue levels of TNF-alpha, IL-1beta and IL-6 were markedly
      increased (p<0.01). The mice treated with HQT extract and SASP recovered
      significantly compared with the TNBS group (p<0.01). CONCLUSION: Our results
      suggested that the efficacy of HQT extract, especially at the higher dose, was
      analogous to that of SASP, which implicated its potential application as a
      natural alternative medicine in colitis treatment.

PMID- 25576894
TI  - Anti-obesity effect of total phenylpropanoid glycosides from Ligustrum robustum
      Blume in fatty diet-fed mice via up-regulating leptin.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In Chinese folk medicine, the leaves of Ligustrum
      robustum Blume (LR) were commonly used in the treatment of obesity and
      hyperlipidemia. This study aimed to evaluate the anti-obesity effect and
      mechanisms of total phenylpropanoid glycosides from Ligustrum robustum Blume
      (LRTPG) in fatty diet-fed C57BL/6J mice. MATERIALS AND METHODS: C57BL/6J mice
      were divided randomly into 6 groups, i.e., control, model, positive (Orlistat
      0.12g/kg), and LRTPG at three dosages (0.3, 0.6 or 1.2g/kg), respectively.
      Control mice were fed with standard diet; the others were fed with fatty diet.
      After 4 weeks' modeling, therapy mice were intragastrically administrated with
      positive drug or LRTPG for 5 weeks, respectively. Pharmacodynamic effects
      including body weight, fat weight, Lee's index, serum lipid levels, morphological
      changes and adipocyte area ratio were evaluated. The mechanisms were explored as
      the factors related to lipids metabolism in gene expressions by real-time PCR,
      and assured as the protein level of differential gene by Western blotting.
      RESULTS: The anti-obesity effects of LRTPG in all treated mice were shown as
      decreased body weight, fat mass, Lee's index, total cholesterol (TC) level, and
      adipocyte area. The mechanisms were demonstrated as elevated mRNA and protein
      levels of adipose leptin, and consequently decreasing mRNA of adipose acyl
      coenzyme A: diacylglycerol acyltransferase (DGAT) with increasing mRNA of hepatic
      cholesterol 7alpha-hydroxylase (CYP7A1), which led to inhibition of triglyceride
      (TG) synthesis and promotion of cholesterol catabolism. CONCLUSIONS: The anti
      obesity effect of LRTPG in fatty diet-fed mice was related to the up-regulation
      of leptin, which may provide scientific evidence supporting the traditional usage
      of LR on obesity in China.

PMID- 25576895
TI  - Ethnopharmacological surveys and pharmacological studies of plants used in
      traditional medicine in the treatment of HIV/AIDS opportunistic diseases in
      Gabon.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological surveys were conducted in
      two regions of Gabon. This led to highlighting some of the medicinal plants used
      by local populations in the management of HIV/AIDS opportunistic diseases. Two
      regions with the highest occurrence of HIV/AIDS cases were visited and
      ethnopharmarcological data was gathered. These regions were the Estuaire Province
      (Libreville and its neighborhood) and the Haut-Ogooue Province (Franceville and
      its neighborhood). The opportunistic diseases and symptomatic conditions
      considered during this study were: diarrhea, respiratory tract infections, cough,
      tuberculosis, abscesses, stomach ache, skin rashes, venereal diseases, typhoid
      fever, anemia, general tiredness, hepatitis and vomiting. MATERIALS AND METHODS:
      The reported species were evaluated through three parameters: specificity,
      reliability and frequency. Plant parts of relevant species were harvested and
      extracted with an aqueous alcohol solution (ethanol/water: 1/1). The extracts
      obtained were submitted to phytochemical screening and in vitro microbiological
      assays on some clinical isolates and ATCC strains, involved in HIV/AIDS
      opportunistic diseases through the Agar well diffusion and Microbroth dilution
      methods. RESULTS: Among the 52 species identified during this survey, Coelocaryon
      klainei Pierre ex Heckel (Myristicaceae), Dacryodes klaineana (Pierre) H.J. Lam
      (Bursecaceae), Phyllanthus diandrus Pax (Euphorbiaceae), Saccoglotys gabonensis
      (Baill.) Urb. (Humiriaceae) and Tetrorchidium didymostemon (Baill.) Pax & K.
      Hoffm. (Euphorbiaceae) were submitted to in vitro microbiological assays.
      Phyllanthus diandrus bark and leaves show best antibacterial activities against
      Pseudomonas aeruginosa and Klebsiella pneumoniae with MIC value of 0.25
      respectively. Phytochemical screening revealed the presence in all the plant
      parts extracts of potentially bioactive molecules, including polyphenols,
      especially flavonoids and tannins. CONCLUSION: It is concluded that some of these
      plants might be submitted to further scientific studies, including the
      identification and isolation of bioactive principles, that could be developed to
      drugs for the treatment of HIV/AIDS opportunistic diseases.

PMID- 25576896
TI  - Pharmacokinetic profiles of hydroxysafflor yellow A following intravenous
      administration of its pure preparations in healthy Chinese volunteers.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hydroxysafflor yellow A (HSYA), the major active
      marker compound isolated from Carthamus tinctorius L., has been demonstrated to
      possess various attractive pharmacological activities. However, there is a lack
      of information about the complete clinical pharmacokinetic profiles of HSYA
      following the administration of its pure preparations. The purpose of this study
      was to fully characterize the pharmacokinetic (PK) properties of HSYA in healthy
      Chinese volunteers following drip intravenous infusion of injectable powder of
      pure HSYA (IPPH), a new drug recently approved for the phase I clinical study by
      China Food and Drug Administration. MATERIALS AND METHODS: 36 healthy subjects of
      either sex were recruited in this single-center, and open-label, single doses
      (25, 50, and 75 mg) and multiple doses (50 mg, once daily, 7 consecutive days)
      study. Plasma samples were analyzed with a validated LC-MS/MS method. Various PK
      parameters were estimated from the plasma concentration versus time data using
      non-compartmental methods. RESULTS: After single dose administration of IPPH, the
      values of AUC(0-t), AUC(0-infinity) and C(max) for HSYA were statistically
      proportional over the dose range of 25-75 mg. After 7 repeated doses of 50 mg
      IPPH, both C(max) and AUC(0-infinity) were significantly decreased, from 3207 to
      2959 MUg L(-1), and from 12,811 to 12,135 ug h L(-1) respectively, while t(1/2)
      was significantly prolonged from 3.912 to 4.414 h. The minimum plasma
      concentrations on day 5, 6 and 7 showed good stability with no significant
      difference. Both Cmax and AUC of HSYA in male volunteers were generally lower
      than that in females. IPPH was generally well tolerated in healthy volunteers by
      either single or multiple dosing. CONCLUSION: HSYA displayed moderately linear PK
      properties over the doses ranging from 25 to 75 mg of IPPH. Repeated
      administration of IPPH once daily could not lead to the in-vivo drug
      accumulation, but significantly affect PK behavior of HSYA. Gender difference
      should be considered for dosage recommendation in the clinic.

PMID- 25576897
TI  - Chemical characterization and biological activity of Chaga (Inonotus obliquus), a
      medicinal "mushroom".
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In Russian traditional medicine, an extract from
      the mushroom Inonotus obliquus (Fr.) Pil'at is used as an anti-tumor medicine and
      diuretic. It has been reported that Inonotus obliquus has therapeutic effects,
      such as anti-inflammatory, immuno-modulatory and hepatoprotective effects. This
      study was designed to investigate the chemical composition and biological
      properties of aqueous and ethanolic extracts of Inonotus obliquus from Finland,
      Russia, and Thailand. Their antioxidative, antimicrobial, and antiquorum
      properties were tested as well as the cytotoxicity on various tumor cell lines.
      MATERIALS AND METHODS: The tested extract was subjected to conventional chemical
      study to identified organic acids and phenolic compounds. Antioxidative activity
      was measured by several different assays. Antimicrobial potential of extracts was
      tested by microdilution method, and antiquorum sensing activity and antibiofilm
      formation of Inonotus obliquus extracts was tested on Pseudomonas aeruginosa.
      Cytotoxicity of the extracts was tested on tumor cells (MCF-7, NCI-H460, HeLa and
      HepG2) and non-tumor liver cells primary cultures. RESULTS: Oxalic acid was found
      as the main organic acid, with the highest amount in the aqueous extract from
      Russia. Gallic, protocatechuic and p-hydroxybenzoic acids were detected in all
      samples. Inonotus obliquus extracts showed high antioxidant and antimicrobial
      activity. Extracts were tested at subMIC for anti-quorum sensing (AQS) activity
      in Pseudomonas aeruginosa and all extracts showed definite AQS activity. The
      assays were done using twitching and swarming of bacterial cultures, and the
      amount of produced pyocyanin as QS parameters. All the extracts demonstrated
      cytotoxic effect on four tumor cell lines and not on primary porcine liver cells
      PLP2. CONCLUSIONS: As the Inonotus obliquus presence in Chaga conks is limited,
      further purification is necessary to draw quantitative conclusions. The presence
      of AQS activity in medicinal mushrooms suggests a broader anti-infectious disease
      protection than only immunomodulatory effects.

PMID- 25576898
TI  - Phenolic composition and effects on allergic contact dermatitis of phenolic
      extracts Sapium sebiferum (L.) Roxb. leaves.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Sapium sebiferum (L.) Roxb. have
      long been used in Traditional Chinese Medicine (TCM) for the treatment of eczema,
      shingles, edema, swelling, ascites, scabs, and snakebites, among other maladies.
      The present study was an outreach research behind our previous study and aimed to
      analyze the chemical composition of phenolic extracts of Sapium sebiferum leaves
      and evaluate their effects on allergic contact dermatitis (ACD). MATERIALS AND
      METHODS: The main compounds of Sapium sebiferum leaves were identified using UPLC
      PDA method by comparing retention times and UV-vis spectra with those of
      reference standards. Their effects on ACD were examined using a
      dinitrofluorobenzene (DNFB) induced mice ACD model. Chemical parameters including
      reactive oxygen species (ROS), MDA and GSH/T-GSH ratio of ear tissue were also
      determined. RESULTS: Seven compounds including gallic acid, ellagic acid,
      hyperin, isoquercitrin, astragalin, quercetin and kaempferol were identified from
      Sapium sebiferum leaves, and their contents were also determined; ellagic acid,
      isoquercitrin and astragalin were in the majority. Phenolic extracts of Sapium
      sebiferum leaves exhibited dose-dependent inhibitory effects on edema induced by
      ACD at doses of 0.03, 0.1 and 0.3 mg/ear. The application of extracts also
      decreased ROS and MDA levels and increased GSH/T-GSH ratio of ear tissue.
      CONCLUSION: The present study demonstrated that the bioactivity of Sapium
      sebiferum leaves may be due to the existence of the identified phenolic
      components, and several high polarity compounds were also active. The beneficial
      effect of Sapium sebiferum leaves on skin diseases is based on its antioxidant
      activity or effects on antioxidant defense system.

PMID- 25576900
TI  - Traumatic atlantoaxial dislocation with Hangman fracture.
AB  - BACKGROUND CONTEXT: Traumatic bilateral-atlantoaxial dislocations are rare
      injuries. Hangman fractures, conversely, represent 4% to 7% of all cervical
      fractures and frequently involve a combination C1-C2 fracture pattern. Presently,
      there is no report in the English literature of a traumatic C2-spondylolisthesis
      associated with a C1-C2 rotatory dislocation. This injury complex cannot be
      cataloged using current classification schemes and no established treatment
      recommendations exist. PURPOSE: To report a unique case of a Hangman fracture
      associated with bilateral C1-C2 rotatory-dislocation, which does not fit into
      existing classification systems, and discuss our treatment approach. STUDY
      DESIGN: A clinical case report and review of the literature. METHODS: Chart
      review and analysis of relevant literature. There were no study-specific
      conflicts of interest. RESULTS: A 26-year-old man sustained a traumatic C2
      spondylolisthesis along with C1-C2 rotatory subluxation in an automobile
      collision. The patient was originally placed in a halo crown and vest and then
      taken for an open reduction and stabilization through a posterior approach for
      persistent C1-C2 subluxation. The patient is currently 16 months postoperative
      and back to work as a plumber. CONCLUSIONS: The injury complex encountered cannot
      be described using the available classification systems. Our treatment included
      initial stabilization with halo placement, followed by a posterior C1, C2, and C3
      segmental reduction and fixation resulting in radiographic fusion and a good
      clinical outcome.

PMID- 25576899
TI  - Characterization of the mutational landscape of anaplastic thyroid cancer via
      whole-exome sequencing.
AB  - Anaplastic thyroid carcinoma (ATC) is a frequently lethal malignancy that is
      often unresponsive to available therapeutic strategies. The tumorigenesis of ATC
      and its relationship to the widely prevalent well-differentiated thyroid
      carcinomas are unclear. We have analyzed 22 cases of ATC as well as 4 established
      ATC cell lines using whole-exome sequencing. A total of 2674 somatic mutations
      (121/sample) were detected. Ontology analysis revealed that the majority of
      variants aggregated in the MAPK, ErbB and RAS signaling pathways. Mutations in
      genes related to malignancy not previously associated with thyroid tumorigenesis
      were observed, including mTOR, NF1, NF2, MLH1, MLH3, MSH5, MSH6, ERBB2, EIF1AX
      and USH2A; some of which were recurrent and were investigated in 24 additional
      ATC cases and 8 ATC cell lines. Somatic mutations in established thyroid cancer
      genes were detected in 14 of 22 (64%) tumors and included recurrent mutations in
      BRAF, TP53 and RAS-family genes (6 cases each), as well as PIK3CA (2 cases) and
      single cases of CDKN1B, CDKN2C, CTNNB1 and RET mutations. BRAF V600E and RAS
      mutations were mutually exclusive; all ATC cell lines exhibited a combination of
      mutations in either BRAF and TP53 or NRAS and TP53. A hypermutator phenotype in
      two cases with >8 times higher mutational burden than the remaining mean was
      identified; both cases harbored unique somatic mutations in MLH mismatch-repair
      genes. This first comprehensive exome-wide analysis of the mutational landscape
      of ATC identifies novel genes potentially associated with ATC tumorigenesis, some
      of which may be targets for future therapeutic intervention. 

PMID- 25576901
TI  - The value of lumbar dorsal root ganglion blocks in predicting the response to
      decompressive surgery in patients with diagnostic doubt.
AB  - BACKGROUND CONTEXT: Pain as a consequence of nerve root compression may not be
      easy to diagnose. Degenerative changes causing nerve root compression on magnetic
      resonance imaging (MRI) are common but not necessarily symptomatic while the
      distribution of pain attributable to a particular nerve root is variable.
      Selective dorsal root ganglion blocks (DRGBs) have been used in these situations
      to aid the diagnostic process, although their use remains controversial. PURPOSE:
      We sought to investigate the positive predictive value of DRGBs in predicting
      response to decompressive surgery on a particular nerve root in a patient cohort
      with diagnostic uncertainty after clinical examination and MRI. STUDY
      DESIGN/SETTING: This was a retrospective review of prospectively collected data
      on 100 consecutive patients. METHODS: One hundred consecutive patients who
      underwent diagnostic DRGB under the senior author were identified
      retrospectively. Clinical records were reviewed for the reason for diagnostic
      uncertainty, level assessed, whether the DRGB reproduced pain typical for the
      patient's symptoms, whether there was anatomically appropriate sensory and motor
      disturbance, whether good pain relief was achieved, and whether they had good
      response to surgery. RESULTS: Of 100 patients recruited, four were removed from
      analysis owing to inadequate surgical decompression proven on postoperative MRI.
      Of the remaining 96 patients, 74 achieved immediate relief in their symptoms
      after DRGB. Fifty-one patients underwent surgical decompression after a
      successful root block; 41 patients achieved a good result from this surgery, and
      10 did not. Nine patients who had no relief in their symptoms from DRGB still
      underwent surgery to decompress the same nerve root; six patients had relief of
      their symptoms from surgery, two did not respond, and one was lost to follow-up.
      The most common reason for diagnostic uncertainty was multilevel disease (74%)
      followed by patients with atypical pain (23%). The most common level assessed was
      the L5 nerve root. The positive predictive value was found to be 80.4%, the
      negative predictive value was 22.2%, with a sensitivity of 85.4% and a
      specificity of 16.7%. CONCLUSIONS: In patients with diagnostic doubt, a positive
      DRGB is a good predictor of a positive outcome after surgery to decompress that
      nerve root. However, the negative predictive value is poor. This result could
      almost certainly be improved if there was a better definition of what constitutes
      a positive, and more importantly a negative, DRGB result. In the meantime, DRGBs
      are a useful adjunct in predicting the outcome of decompressive surgery in people
      with pain as a consequence of potential lumbosacral nerve root compression.

PMID- 25576902
TI  - Assessment of stress patterns on a spinal motion segment in healthy versus
      osteoporotic bony models with or without disc degeneration: a finite element
      analysis.
AB  - BACKGROUND CONTEXT: With an increasing prevalence of low back pain, physicians
      strive to optimize the treatment of patients with degenerated motion segments.
      There exists a consensus in literature that osteoporotic patients exhibit
      nonphysiologic loading patterns, while degenerated intervertebral discs (IVDs)
      are also believed to alter spine biomechanics. PURPOSE: To evaluate alterations
      occurring in lumbosacral spine biomechanics of an osteoporotic model, with or
      without IVD degeneration, when compared with a healthy spine segment. STUDY
      DESIGN: The investigation was based on finite element (FE) analysis of a patient
      specific lumbosacral spine model. METHODS: A biorealistic model of a lumbosacral
      spine segment is introduced to determine the morbidity of disc degeneration and
      osteoporosis. The model was verified and validated for the purpose of the study
      and subjected to a dynamic FE analysis, considering anisotropic bone properties
      and solid ligamentous tissue. RESULTS: The yielded results merit high clinical
      interest. Osteoporosis resulted in a nonuniform increase of facet joint loading,
      which was even more pronounced in the scenario simulating a degenerated disc. The
      results also revealed an enslavement of intradiscal pressure to the disc state
      (in the degenerated and superior adjacent level). CONCLUSIONS: The investigation
      presented refined insight into the dynamic biomechanical response of a
      degenerated spine segment. The increase in the calculated occurring stresses was
      considered as critical in the motion segment adjacent and superior to the
      degenerated one. This suggests that prevalent trauma in a motion segment may be a
      symptomatic condition of a poorly treated formal pathology in the inferior spine
      level.

PMID- 25576903
TI  - Radiation exposure during scoliosis surgery: a prospective study.
AB  - BACKGROUND CONTEXT: The present literature on the cancer risks related to
      radiation exposure in patients and surgeons during scoliosis surgery is sparse.
      PURPOSE: To assess the radiation exposure in patients and surgeons during
      scoliosis surgery and estimate the increased cancer risk of both groups. STUDY
      DESIGN: Over a 6-month period, we conducted a prospective study to monitor the
      intraoperative radiation dose received by both patients and surgeons during
      scoliosis cases. PATIENT SAMPLE: It included 30 consecutive patients undergoing
      scoliosis surgery by a team of two surgeons (S1 and S2). OUTCOME MEASURES: We
      measured the radiation exposure to the eyes, thyroid, and hands for each surgeon;
      measured the difference of radiation exposure between the two surgeons; the
      difference in radiation exposure with respect to the proximity of the surgeon to
      the X-ray tube, and the radiation exposure for each patient. METHODS: An
      electronic dosimeter was attached over the thyroid guard and a thermoluminescent
      dosimeter ring on both hands of each surgeon. The patients were monitored using
      the dose area product (DAP) measurements from the image intensifier, and their
      radiation exposure was calculated with the Monte Carlo calculation. RESULTS: The
      mean eye dose per procedure for the two surgeons S1 and S2 was 0.8 MUSv and 1.3
      MUSv, respectively. The mean thyroid dose for S2 and S1 was 1.2 MUSv and 1.4
      MUSv, respectively. The dose recorded by the surgeon on the same side of the
      patient as the X-ray tube was significantly higher than for the surgeon on the
      far side (p<.05). Mean DAP per procedure was 91.3 cGycm(2) and the mean radiation
      dose for patients was 252.9 MUSv. The increase in cancer risk for patients and
      surgeons was 0.001% and 0.0005%, respectively, for each year of exposure.
      CONCLUSIONS: A significantly higher dose of radiation during scoliosis surgery
      was received by the surgeon standing on the same side as the X-ray tube. However,
      both surgeons received a total radiation dose of less than 1% of the recommended
      dose limit per year and, therefore, the total radiation exposure in both surgeons
      and patients was well within the recommended safe limits.

PMID- 25576904
TI  - Leptin exerts proliferative and anti-apoptotic effects on goose granulosa cells
      through the PI3K/Akt/mTOR signaling pathway.
AB  - Leptin was known as a pivotal regulator for the control of food intake and energy
      expenditure. However, leptin has also been found to be involved in the regulation
      of female reproductive system through interactions with pathways in the
      hypothalamic-hypophyseal axis and direct action at the ovarian level. In the
      present study, granulosa cells from goose ovarian preovulatory (F1-F3) follicles
      were cultured with leptin (0, 1, 10 or 100ng/ml). The proliferative and anti
      apoptotic actions of leptin in granulosa cells were revealed by CCK-8, BrdU and
      TUNEL assays. Quantitative real-time PCR and Western blot analyses further
      indicated that leptin treatment led to increased expression of cyclin D1, cyclin
      D2, cyclin D3 and bcl-2, and decreased expression of p21 and caspase-3. The
      effects were involved in the activation of the PI3K/Akt/mTOR signaling pathway,
      as leptin treatment enhanced the expression of PI3K, Akt1, Akt2, Raptor, mTOR,
      S6K and p-S6K. Moreover, blockade of the PI3K/Akt/mTOR pathway attenuated the
      influences of leptin on proliferation and apoptosis of granulosa cells,
      considering that activated factors by leptin were inhibited in the presence of
      either 20MUM LY294002 (a PI3K inhibitor) or 10MUM rapamycin (an mTOR inhibitor).
      In addition, leptin had a modulatory effect on the expression of its receptor at
      the transcriptional and translational levels, and blockade of PI3K/Akt/mTOR
      inhibited both basal and leptin-induced Lepr gene and protein expression. These
      findings suggest that leptin exerts its proliferative and anti-apoptotic effects
      on goose granulosa cells through the PI3K/Akt/mTOR signaling pathway via
      interaction with its receptor. 

PMID- 25576905
TI  - VDR FokI polymorphism is associated with a reduced T-helper cell population under
      vitamin D stimulation in type 1 diabetes patients.
AB  - BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease mediated by T-helper
      (Th) cells. Additionally, the immune system regulator vitamin D, exerts its
      modulatory effects through the vitamin D receptor (VDR) expressed in Th cells.
      Furthermore, several genetic variants in the VDR gene including the VDR FokI
      (rs10735810) polymorphism have been implicated in T1D susceptibility in some
      Caucasian populations. Aim of the present study was to investigate the possible
      functional role of the VDR FokI gene polymorphism in Th cells from T1D patients
      and healthy controls (HC). METHODS: Isolated Th cells from 23 HC and 20 T1D
      patients were stimulated for 72h with 25-hydroxyvitamin D3 (25(OH)D3) and 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3). After in vitro culture CD3(+)CD4(+) (CD4(+))
      Th cell subsets were characterized by flow cytometry and gene expression of VDR
      was measured by Taqman assay. Finally, the VDR FokI polymorphism was genotyped.
      RESULTS: Significant lower VDR gene expression was observed in non-stimulated and
      25(OH)D3 stimulated Th cells from T1D compared to HC (p=0.04 and p=0.005,
      respectively). In addition, by stratifying subjects into VDR FokI genotypes,
      significant lower percentage of CD4(+) cells was observed in 25(OH)D3 and
      1,25(OH)2D3 stimulated Th cells from T1D patients carrying the "FF" genotype
      compared to those with the genotypes "Ff/ff" (p=0.02 and p=0.05, respectively).
      Moreover, looking at vitamin D effects according to VDR FokI genotypes, CD4(+)
      cells were significantly down-regulated by 25(OH)D3 and 1,25(OH)2D3 only in T1D
      "FF" carriers (p=0.01 and p=0.02; respectively). CONCLUSION: According to these
      results, T1D patients carrying the "FF" genotype with an adequate vitamin D
      therapy may benefit from a more balanced T cell immunity. However, further
      research is needed to confirm these premilinary findings and to elucidate
      functional mechanisms of genetic variation in the vitamin D system. This article
      is part of a Special Issue entitled '17th Vitamin D Workshop'.

PMID- 25576906
TI  - Progesterone attenuates Abeta(25-35)-induced neuronal toxicity via JNK
      inactivation and progesterone receptor membrane component 1-dependent inhibition
      of mitochondrial apoptotic pathway.
AB  - Progesterone, which acts as a neurosteroid in nervous system, has been shown to
      have neuroprotective effects in different experiments in vitro and in vivo. Our
      previous study demonstrates that progesterone exerts neuroprotections in
      Alzheimer's disease-like rats. Present study attempted to evaluate the protective
      effects of progesterone on Abeta-treated neurons and potential mechanisms
      involved in neuroprotection. Results showed that treatment with progesterone
      protected primary cultured rat cortical neurons against Abeta(25-35)-induced
      apoptosis. Furthermore, we observed that progesterone alleviated mitochondrial
      dysfunction by rescuing mitochondrial membrane potential under Abeta challenge.
      Moreover, progesterone could also attenuate Bax/Bcl-2 proteins ratio upregulation
      and inhibit the activation of caspase-3 in Abeta-treated neurons. These indicate
      that progesterone attenuates Abeta(25-35)-induced neuronal toxicity by inhibiting
      mitochondria-associated apoptotic pathway. Both classic progesterone receptors
      (classic PR) and progesterone receptor membrane component 1 (PGRMC1), a special
      progesterone membrane receptor, are broadly expressed throughout the brain. The
      protective effect of progesterone was partially abolished by PGRMC1 inhibitor
      AG205 rather than classic PR antagonist RU486 in this study. Additionally,
      progesterone protected neurons by inhibiting Abeta-induced activation of JNK,
      which was an upstream signaling component in Abeta-induced mitochondria
      associated apoptotic pathway. But this process was independent of PGRMC1. Taken
      together, these results suggest that progesterone exerts a protective effect
      against Abeta(25-35)-induced insults at least in part by two complementary
      pathways: (1) progesterone receptor membrane component 1-dependent inhibition of
      mitochondrial apoptotic pathway, and (2) blocking Abeta-induced JNK activation.
      The present study provides new insights into the mechanism by which progesterone
      brings neuroprotection. This article is part of a Special Issue entitled
      'Steroids & Nervous System'.

PMID- 25576907
TI  - Compensatory fronto-parietal hyperactivation during set-shifting in unmedicated
      patients with Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) often suffer from impairments in executive
      functions, such as mental rigidity, which can be measured as impaired set
      shifting. Previous studies have shown that set-shifting deficits in patients with
      PD result from hypo-excitation of the caudate nucleus and lateral prefrontal
      cortices. The results of these studies may have been influenced by the inclusion
      of patients on dopaminergic medication, and by choosing set-shifting paradigms in
      which performance also depends on other cognitive mechanisms, such as matching-to
      sample. To circumvent these potential confounding factors, we tested patients
      with PD that were not on dopamine replacement therapy, and we developed a new
      feedback-based paradigm to measure the cognitive construct set-shifting more
      accurately. In this case-control study, 18 patients with PD and 35 well-matched
      healthy controls performed the set-shifting task, while task-related neural
      activation was recorded using functional magnetic resonance imaging.
      Behaviourally, PD patients, compared with healthy controls, made more errors
      during repeat trials, but not set-shift trials. The patients, compared with
      controls, showed increased task-related activation of the bilateral inferior
      parietal cortex, and the right superior frontal gyrus, and decreased activation
      of the right ventrolateral prefrontal cortex during set-shift trials. Our
      findings suggest that, despite decreased task-related activation of the right
      ventrolateral prefrontal cortex, these early-stage unmedicated patients with PD
      do not yet suffer from set-shifting deficits due to compensatory hyperactivation
      in the inferior parietal cortex and the superior frontal gyrus. 

PMID- 25576908
TI  - Pushing to the limits: the dynamics of cognitive control during exhausting
      exercise.
AB  - This study aimed at investigating concurrent changes in cognitive control and
      cerebral oxygenation (Cox) during steady intense exercise to volitional
      exhaustion. Fifteen participants were monitored using prefrontal near-infrared
      spectroscopy and electromyography of the thumb muscles during the completion of
      an Eriksen flanker task completed either at rest (control condition) or while
      cycling at a strenuous intensity until exhaustion (exercise condition). Two time
      windows were matched between the conditions to distinguish a potential exercise
      induced evolutive cognitive effect: an initial period and a terminal period. In
      the initial period, Cox remained unaltered and, contrary to theoretical
      predictions, exercise did not induce any deficit in selective response
      inhibition. Rather, the drop-off of the delta curve as reaction time lengthened
      suggested enhanced efficiency of cognitive processes in the first part of the
      exercise bout. Shortly before exhaustion, Cox values were severely reduced -
      though not characteristic of a hypofrontality state - while no sign of deficit in
      selective response inhibition was observed. Despite this, individual's
      susceptibility to making fast impulsive errors increased and less efficient
      online correction of incorrect activation was observed near exhaustion. A
      negative correlation between Cox values and error rate was observed and is
      discussed in terms of cerebral resources redistribution. 

PMID- 25576909
TI  - Sustained meaning activation for polysemous but not homonymous words: evidence
      from EEG.
AB  - Theoretical linguistic accounts of lexical ambiguity distinguish between
      homonymy, where words that share a lexical form have unrelated meanings, and
      polysemy, where the meanings are related. The present study explored the
      psychological reality of this theoretical assumption by asking whether there is
      evidence that homonyms and polysemes are represented and processed differently in
      the brain. We investigated the time-course of meaning activation of different
      types of ambiguous words using EEG. Homonyms and polysemes were each further
      subdivided into two: unbalanced homonyms (e.g., "coach") and balanced homonyms
      (e.g., "match"); metaphorical polysemes (e.g., "mouth") and metonymic polysemes
      (e.g., "rabbit"). These four types of ambiguous words were presented as primes in
      a visual single-word priming delayed lexical decision task employing a long ISI
      (750 ms). Targets were related to one of the meanings of the primes, or were
      unrelated. ERPs formed relative to the target onset indicated that the
      theoretical distinction between homonymy and polysemy was reflected in the N400
      brain response. For targets following homonymous primes (both unbalanced and
      balanced), no effects survived at this long ISI indicating that both meanings of
      the prime had already decayed. On the other hand, for polysemous primes (both
      metaphorical and metonymic), activation was observed for both dominant and
      subordinate senses. The observed processing differences between homonymy and
      polysemy provide evidence in support of differential neuro-cognitive
      representations for the two types of ambiguity. We argue that the polysemous
      senses act collaboratively to strengthen the representation, facilitating
      maintenance, while the competitive nature of homonymous meanings leads to decay.

PMID- 25576910
TI  - Developmental patterns of expressive language hemispheric lateralization in
      children, adolescents and adults using functional near-infrared spectroscopy.
AB  - The development of language hemispheric specialization is not well understood in
      young children, especially regarding expressive language functions. In this
      study, we investigated age-related changes in expressive language lateralization
      patterns in a population of children (3-6 and 7-10 years old), adolescents (11-16
      years old), and young adults (19-30 years old). During functional near-infrared
      spectroscopy recordings, all participants performed a verbal fluency task, which
      consisted in naming as many words as possible belonging to a given semantic
      category. Hemoglobin concentration changes were measured in bilateral frontal and
      temporal cortical areas. During the language task, results showed a strong left
      hemisphere response along with weaker right hemisphere activation in all groups.
      Age-related increases in hemodynamic responses were found bilaterally, with
      younger children showing smaller hemodynamic responses than adolescents and
      adults in both hemispheres. Overall, these findings confirm that a left
      hemisphere specialization is already established in young children and persists
      through adulthood. Early left hemisphere specialization for expressive language
      suggests that language development hinges on structural and functional properties
      of the human brain with little reorganization occurring with development. 

PMID- 25576911
TI  - Severe dental fluorosis and cognitive deficits.

PMID- 25576913
TI  - A microRNA-1280/JAG2 network comprises a novel biological target in high-risk
      medulloblastoma.
AB  - Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high
      risk medulloblastoma (MB) pathogenesis. However, the exact biological functions
      of PDGFRalpha and PDGFRbeta signaling in MB biology remain poorly understood.
      Here, we report the subgroup specific expression of PDGFRalpha and PDGFRbeta and
      their associated biological pathways in MB tumors. c-MYC, a downstream target of
      PDGFRbeta but not PDGFRalpha, is involved in PDGFRbeta signaling associated with
      cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRbeta
      and c-MYC blocks MB cell proliferation and migration synergistically. Integrated
      analysis of miRNA and miRNA targets regulated by both PDGFRbeta and c-MYC reveals
      that increased expression of JAG2, a target of miR-1280, is associated with high
      metastatic dissemination at diagnosis and a poor outcome in MB patients. Our
      study may resolve the controversy on the role of PDGFRs in MB and unveils JAG2 as
      a key downstream effector of a PDGFRbeta-driven signaling cascade and a potential
      therapeutic target. 

PMID- 25576914
TI  - alpha-Radioimmunotherapy with 213Bi-anti-CD38 immunoconjugates is effective in a
      mouse model of human multiple myeloma.
AB  - In spite of development of molecular therapeutics, multiple myeloma (MM) is fatal
      in most cases. CD38 is a promising target for selective treatment of MM. We
      tested radioimmunoconjugates consisting of the alpha-emitter 213Bi coupled to an
      anti-CD38 MAb in preclinical treatment of MM. Efficacy of 213Bi-anti-CD38-MAb was
      assayed towards different MM cell lines with regard to induction of DNA double
      strand breaks, induction of apoptosis and initiation of cell cycle arrest.
      Moreover, mice bearing luciferase-expressing MM xenografts were treated with
      213Bi-anti-CD38-MAb. Therapeutic efficacy was monitored by bioluminescence
      imaging, overall survival and histology. 213Bi-anti-CD38-MAb treatment induced
      DNA damage which did not result in activation of the G2 DNA-damage-response
      checkpoint, but instead in mitotic arrest and subsequent mitotic catastrophe. The
      anti-tumor effect of 213Bi-anti-CD38-MAb correlated with the expression level of
      CD38 in each MM cell line. In myeloma xenografts, treatment with 213Bi-anti-CD38
      MAb suppressed tumor growth via induction of apoptosis in tumor tissue and
      significantly prolonged survival compared to controls. The major organ systems
      did not show any signs of 213Bi-induced toxicity. Preclinical treatment of MM
      with 213Bi-anti-CD38-MAb turned out as an effective therapeutic option.

PMID- 25576915
TI  - Multiple receptor tyrosine kinase activation attenuates therapeutic efficacy of
      the fibroblast growth factor receptor 2 inhibitor AZD4547 in FGFR2 amplified
      gastric cancer.
AB  - Fibroblast growth factor receptor 2 (FGFR2)-targeted therapy has attracted
      considerable attention as novel anticancer agents in gastric cancer (GC).
      However, intrinsic or acquired drug resistance has emerged as a major challenge
      to their clinical use. In this study, we demonstrated that several receptor
      tyrosine kinase (RTK), including EGFR, HER3 and MET, activations contributed to
      AZD4547 (a selective FGFR2 inhibitor) hyposensitivity in FGFR2 amplified GC
      cells. The rescue effect was abrogated by inhibiting these RTKs with their
      targeted tyrosine kinase inhibitors (TKIs). In addition, synergy in growth
      inhibition was observed when the GC cells were treated with a combination of
      AZD4547 and cetuximab (an EGFR monoclonal antibody) both in vitro and in vivo.
      More importantly, tissue microarray analysis revealed that these resistance
      conferring RTKs were highly expressed in FGFR2 positive GC patients. Taken
      together, these observations demonstrated RTKs including EGFR, HER3 and MET
      activations as novel mechanisms of hyposensitivity to AZD4547. It will be
      clinically valuable to investigate the involvement of RTK-mediated signaling in
      intrinsicor acquired resistance to FGFR2 TKIs in GC. A combination targeted
      therapeutic strategy may be recommended for treating FGFR2 amplified GC patients
      with these RTK activations. 

PMID- 25576916
TI  - Functional repair of p53 mutation in colorectal cancer cells using trans
      splicing.
AB  - Mutation in the p53 gene is arguably the most frequent type of gene-specific
      alterations in human cancers. Current p53-based gene therapy contains the
      administration of wt-p53 or the suppression of mutant p53 expression in p53
      defective cancer cells. . We hypothesized that trans-splicing could be exploited
      as a tool for the correction of mutant p53 transcripts in p53-mutated human
      colorectal cancer (CRC) cells. In this study, the plasmids encoding p53 pre-trans
      splicing molecules (PTM) were transfected into human CRC cells carrying p53
      mutation. The plasmids carrying p53-PTM repaired mutant p53 transcripts in p53
      mutated CRC cells, which resulted in a reduction in mutant p53 transcripts and an
      induction of wt-p53 simultaneously. Intratumoral administration of adenovirus
      vectors carrying p53 trans-splicing cassettes suppressed the growth of tumor
      xenografts. Repair of mutant p53 transcripts by trans-splicing induced cell-cycle
      arrest and apoptosis in p53-defective colorectal cancer cells in vitro and in
      vivo. In conclusion, the present study demonstrated for the first time that trans
      splicing was exploited as a strategy for the repair of mutant p53 transcripts,
      which revealed that trans-splicing would be developed as a new therapeutic
      approach for human colorectal cancers carrying p53 mutation. 

PMID- 25576917
TI  - Ammonium is a key determinant on the dietary restriction of yeast chronological
      aging in culture medium.
AB  - New evidences have recently emerged from studies in yeast and in higher
      eukaryotes showing the importance of nutrient balance in dietary regimes and its
      effects on longevity regulation.We have previously shown that manipulation of
      ammonium concentration in the culture and/or aging medium can drastically affect
      chronological lifespan (CLS)of Saccharomyces cerevisiae, especially in amino acid
      restricted cells. Here we describe that the CLS shortening under amino acid
      restriction can be completely reverted by removing ammonium from the culture
      medium. Furthermore, the absence of ammonium, and of any rich nitrogen source,
      was so effective in extending CLS that no beneficial effect could be observed by
      further imposing calorie restriction conditions. When present in the culture
      medium,ammonium impaired the consumption of the auxotrophy-complementing amino
      acids and caused in an improper cell cycle arrest of the culture.TOR1 deletion
      reverted ammonium effects both in amino acid restricted and non-restricted
      cultures, whereas, Ras2p and Sch9p seem to have only a milder effect in the
      mediation of ammonium toxicity under amino acid restriction and no effect on non
      restricted cultures.Our studies highlight ammonium as a key effector in the
      nutritional equilibrium between rich and essential nitrogen sources and glucose
      required for longevity promotion.

PMID- 25576918
TI  - Amyloid precursor-like protein 2 (APLP2) affects the actin cytoskeleton and
      increases pancreatic cancer growth and metastasis.
AB  - Amyloid precursor-like protein 2 (APLP2) is aberrantly expressed in pancreatic
      cancer. Here we showed that APLP2 is increased in pancreatic cancer metastases,
      particularly in metastatic lesions found in the diaphragm and intestine.
      Examination of matched human primary tumor-liver metastasis pairs showed that
      38.1% of the patients had positive APLP2 expression in both the primary tumor and
      the corresponding liver metastasis. Stable knock-down of APLP2 expression (with
      inducible shRNA) in pancreatic cancer cells reduced the ability of these cells to
      migrate and invade. Loss of APLP2 decreased cortical actin and increased
      intracellular actin filaments in pancreatic cancer cells. Down-regulation of
      APLP2 decreased the weight and metastasis of orthotopically transplanted
      pancreatic tumors in nude mice. 

PMID- 25576919
TI  - Co-expression of PKM2 and TRIM35 predicts survival and recurrence in
      hepatocellular carcinoma.
AB  - The identification of prognostic markers for hepatocellular carcinoma (HCC) is
      needed for clinical practice. Tripartite motif-containing 35 (TRIM35) is a tumor
      suppressor of HCC. TRIM35 inhibits phosphorylation of pyruvate kinase isoform M2
      (PKM2), which is involved in aerobic glycolysis of cancer cells. We found that
      expression of PKM2 was significantly increased in HCC tissues. This
      overexpression of PKM2 was correlated with a high TNM stage and level of vascular
      invasion. Patients with HCC who were positive for PKM2 expression and negative
      for TRIM35 expression had shorter overall survival and time to recurrence than
      patients who were negative for PKM2 and positive for TRIM35. Furthermore,
      PKM2/TRIM35 combination was an independent and significant risk factor for
      recurrence and survival. In conclusion, PKM2 (+) and TRIM35 (-) contribute to the
      aggressiveness and poor prognosis of HCC. PKM2/TRIM35 expression could be a
      biomarker for the prognosis of HCC and target for cancer therapy. 

PMID- 25576921
TI  - PARP targeting counteracts gliomagenesis through induction of mitotic catastrophe
      and aggravation of deficiency in homologous recombination in PTEN-mutant glioma.
AB  - Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults
      and one of the most aggressive cancers. PARP-1 is a nuclear protein involved in
      multiple facets of DNA repair and transcriptional regulation. In this study we
      dissected the action of PARP inhibition in different GBM cell lines with either
      functional or mutated PTEN that confers resistance to diverse therapies. In PTEN
      mutant cells, PARP inhibition induced a severe genomic instability, exacerbated
      homologous recombination repair (HR) deficiency and down-regulated the Spindle
      Assembly Checkpoint (SAC) factor BUBR1, leading to mitotic catastrophe (MC). EGFR
      gene amplification also represents a signature of genetic abnormality in GBM. To
      more effectively target GBM cells, co-treatment with a PARP inhibitor and an EGFR
      blocker, erlotinib, resulted in a strong suppression of ERK1/2 activation and in
      vivo the combined effect elicited a robust reduction in tumour development. In
      conclusion, PARP inhibition targets PTEN-deficient GBM cells through accentuation
      of SAC repression and aggravation of HR deficiency, leading to the induction of
      genomic instability and eventually deriving to mitotic catastrophe (MC); the
      inhibition of PARP and co-treatment with an inhibitor of pro-survival pathways
      strongly retarded in vivo gliomagenesis. 

PMID- 25576920
TI  - mTOR kinase inhibitors synergize with histone deacetylase inhibitors to kill B
      cell acute lymphoblastic leukemia cells.
AB  - High activity of the mechanistic target of rapamycin (mTOR) is associated with
      poor prognosis in pre-B-cell acute lymphoblastic leukemia (B-ALL), suggesting
      that inhibiting mTOR might be clinically useful. However, emerging data indicate
      that mTOR inhibitors are most effective when combined with other target agents.
      One strategy is to combine with histone deacetylase (HDAC) inhibitors, since B
      ALL is often characterized by epigenetic changes that silence the expression of
      pro-apoptotic factors. Here we tested combinations of mTOR and pan-HDAC
      inhibitors on B-ALL cells, including both Philadelphia chromosome-positive (Ph+)
      and non-Ph cell lines. We found that mTOR kinase inhibitors (TOR-KIs) synergize
      with HDAC inhibitors to cause apoptosis in B-ALL cells and the effect is greater
      when compared to rapamycin plus HDAC inhibitors. The combination of TOR-KIs with
      the clinically approved HDAC inhibitor vorinostat increased apoptosis in primary
      pediatric B-ALL cells in vitro. Mechanistically, TOR-KI and HDAC inhibitor
      combinations increased expression of pro-death genes, including targets of the
      Forkhead Box O (FOXO) transcription factors, and increased sensitivity to
      apoptotic triggers at the mitochondria. These findings suggest that targeting
      epigenetic factors can unmask the cytotoxic potential of TOR-KIs towards B-ALL
      cells. 

PMID- 25576922
TI  - 12/15 Lipoxygenase regulation of colorectal tumorigenesis is determined by the
      relative tumor levels of its metabolite 12-HETE and 13-HODE in animal models.
AB  - Colorectal cancer (CRC) continues to be a major cause of morbidity and mortality.
      The arachidonic acid (AA) pathway and linoleic acid (LA) pathway have been
      implicated as important contributors to CRC development and growth. Human 15
      lipoxygenase 1 (15-LOX-1) converts LA to anti-tumor 13-S-hydroxyoctadecadienoic
      acid (13-HODE)and 15-LOX-2 converts AA to 15-hydroxyeicosatetraenoic acid (15
      HETE). In addition, human 12-LOX metabolizes AA to pro-tumor 12-HETE. In rodents,
      the function of 12-LOX and 15-LOX-1 and 15-LOX-2 is carried out by a single
      enzyme, 12/15-LOX. As a result, conflicting conclusions concerning the role of 12
      LOX and 15-LOX have been obtained in animal studies. In the present studies, we
      determined that PD146176, a selective 15-LOX-1 inhibitor, markedly suppressed 13
      HODE generation in human colon cancer HCA-7 cells and HCA-7 tumors, in
      association with increased tumor growth. In contrast, PD146176 treatment led to
      decreases in 12-HETE generation in mouse colon cancer MC38 cells and MC38 tumors,
      in association with tumor inhibition. Surprisingly, deletion of host 12/15-LOX
      alone led to increased MC38 tumor growth, in association with decreased tumor 13
      HODE levels, possibly due to inhibition of 12/15-LOX activity in stroma.
      Therefore, the effect of 12/15-LOX on colorectal tumorigenesis in mouse models
      could be affected by tumor cell type (human or mouse), relative 12/15 LOX
      activity in tumor cells and stroma as well as the relative tumor 13-HODE and 12
      HETE levels. 

PMID- 25576923
TI  - Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma
      cells.
AB  - We used whole genome microarray analysis to identify potential candidate genes
      with differential expression in BRAFV600E vs NRASQ61R melanoma cells. We
      selected, for comparison, a peculiar model based on melanoma clones, isolated
      from a single tumor characterized by mutually exclusive expression of BRAFV600E
      and NRASQ61R in different cells. This effort led us to identify two genes, SEMA6A
      and MICAL1, highly expressed in BRAF-mutant vs NRAS-mutant clones. Real-time PCR,
      Western blot and immunohistochemistry confirmed preferential expression of Sema6A
      and Mical1 in BRAFV600E melanoma. Sema6A is a member of the semaphorin family,
      and it complexes with the plexins to regulate actin cytoskeleton, motility and
      cell proliferation. Silencing of Sema6A in BRAF-mutant cells caused cytoskeletal
      remodeling, and loss of stress fibers, that in turn induced cell death.
      Furthermore, Sema6A depletion caused loss of anchorage-independent growth,
      inhibition of chemotaxis and invasion. Forced Sema6A overexpression, in NRASQ61R
      clones, induced anchorage-independent growth, and a significant increase of
      invasiveness. Mical1, that links Sema/PlexinA signaling, is also a negative
      regulator of apoptosis. Indeed, Mical-1 depletion in BRAF mutant cells restored
      MST-1-dependent NDR phosphorylation and promoted a rapid and massive NDR
      dependent apoptosis. Overall, our data suggest that Sema6A and Mical1 may
      represent new potential therapeutic targets in BRAFV600E melanoma. 

PMID- 25576924
TI  - Transcriptional regulation of Sox2 by the retinoblastoma family of pocket
      proteins.
AB  - Cellular reprogramming to iPSCs has uncovered unsuspected links between tumor
      suppressors and pluripotency factors. Using this system, it was possible to
      identify tumor suppressor p27 as a repressor of Sox2 during differentiation. This
      led to the demonstration that defects in the repression of Sox2 can contribute to
      tumor development. The members of the retinoblastoma family of pocket proteins,
      pRb, p107 and p130, are negative regulators of the cell cycle with tumor
      suppressor activity and with roles in differentiation. In this work we studied
      the relative contribution of the retinoblastoma family members to the regulation
      of Sox2 expression. We found that deletion of Rb or p130 leads to impaired
      repression of Sox2, a deffect amplified by inactivation of p53. We also
      identified binding of pRb and p130 to an enhancer with crucial regulatory
      activity on Sox2 expression. Using cellular reprogramming we tested the impact of
      the defective repression of Sox2 and confirmed that Rb deficiency allows the
      generation of iPSCs in the absence of exogenous Sox2. Finally, partial depletion
      of Sox2 positive cells reduced the pituitary tumor development initiated by Rb
      loss in vivo. In summary, our results show that Sox2 repression by pRb is a
      relevant mechanism of tumor suppression. 

PMID- 25576925
TI  - Insulin-independent role of adiponectin receptor signaling in Drosophila germline
      stem cell maintenance.
AB  - Adipocytes have key endocrine roles, mediated in large part by secreted protein
      hormones termed adipokines. The adipokine adiponectin is well known for its role
      in sensitizing peripheral tissues to insulin, and several lines of evidence
      suggest that adiponectin might also modulate stem cells/precursors. It remains
      unclear, however, how adiponectin signaling controls stem cells and whether this
      role is secondary to its insulin-sensitizing effects or distinct. Drosophila
      adipocytes also function as an endocrine organ and, although no obvious
      adiponectin homolog has been identified, Drosophila AdipoR encodes a well
      conserved homolog of mammalian adiponectin receptors. Here, we generate a null
      AdipoR allele and use clonal analysis to demonstrate an intrinsic requirement for
      AdipoR in germline stem cell (GSC) maintenance in the Drosophila ovary. AdipoR
      null GSCs are not fully responsive to bone morphogenetic protein ligands from the
      niche and have a slight reduction in E-cadherin levels at the GSC-niche junction.
      Conversely, germline-specific overexpression of AdipoR inhibits natural GSC loss,
      suggesting that reduction in adiponectin signaling might contribute to the normal
      decline in GSC numbers observed over time in wild-type females. Surprisingly,
      AdipoR is not required for insulin sensitization of the germline, leading us to
      speculate that insulin sensitization is a more recently acquired function than
      stem cell regulation in the evolutionary history of adiponectin signaling. Our
      findings establish Drosophila female GSCs as a new system for future studies
      addressing the molecular mechanisms whereby adiponectin receptor signaling
      modulates stem cell fate. 

PMID- 25576926
TI  - Tie1 is required for lymphatic valve and collecting vessel development.
AB  - Tie1 is a receptor tyrosine kinase with broad expression in embryonic
      endothelium. Reduction of Tie1 levels in mouse embryos with a hypomorphic Tie1
      allele resulted in abnormal lymphatic patterning and architecture, decreased
      lymphatic draining efficiency, and ultimately, embryonic demise. Here we report
      that Tie1 is present uniformly throughout the lymphatics and from late
      embryonic/early postnatal stages, becomes more restricted to lymphatic valve
      regions. To investigate later events of lymphatic development, we employed Cre
      loxP recombination utilizing a floxed Tie1 allele and an Nfatc1Cre line, to
      provide loxP excision predominantly in lymphatic endothelium and developing
      valves. Interestingly, unlike the early prenatal defects previously described by
      ubiquitous endothelial deletion, excision of Tie1 with Nfatc1Cre resulted in
      abnormal lymphatic defects in postnatal mice and was characterized by agenesis of
      lymphatic valves and a deficiency of collecting lymphatic vessels. Attenuation of
      Tie1 signaling in lymphatic endothelium prevented initiation of lymphatic valve
      specification by Prox1 high expression lymphatic endothelial cells that is
      associated with the onset of turbulent flow in the lymphatic circulation. Our
      findings reveal a fundamental role for Tie1 signaling during lymphatic vessel
      remodeling and valve morphogenesis and implicate it as a candidate gene involved
      in primary lymphedema. 

PMID- 25576927
TI  - Diverse ETS transcription factors mediate FGF signaling in the Ciona anterior
      neural plate.
AB  - The ascidian Ciona intestinalis is a marine invertebrate belonging to the sister
      group of the vertebrates, the tunicates. Its compact genome and simple,
      experimentally tractable embryos make Ciona well-suited for the study of cell
      fate specification in chordates. Tunicate larvae possess a characteristic
      chordate body plan, and many developmental pathways are conserved between
      tunicates and vertebrates. Previous studies have shown that FGF signals are
      essential for neural induction and patterning at sequential steps of Ciona
      embryogenesis. Here we show that two different ETS family transcription factors,
      Ets1/2 and Elk1/3/4, have partially redundant activities in the anterior neural
      plate of gastrulating embryos. Whereas Ets1/2 promotes pigment cell formation in
      lateral lineages, both Ets1/2 and Elk1/3/4 are involved in the activation of
      Myt1L in medial lineages and the restriction of Six3/6 expression to the anterior
      most regions of the neural tube. We also provide evidence that photoreceptor
      cells arise from posterior regions of the presumptive sensory vesicle, and do not
      depend on FGF signaling. Cells previously identified as photoreceptor progenitors
      instead form ependymal cells and neurons of the larval brain. Our results extend
      recent findings on FGF-dependent patterning of anterior-posterior compartments in
      the Ciona central nervous system. 

PMID- 25576928
TI  - Wnt7b is required for epithelial progenitor growth and operates during epithelial
      to-mesenchymal signaling in pancreatic development.
AB  - Wnt signaling is a well conserved pathway critical for growth, patterning and
      differentiation of multiple tissues and organs. Previous studies on Wnt signaling
      in the pancreas have been based predominantly on downstream pathway effector
      genes such as beta-catenin. We here provide evidence that the canonical-pathway
      member Wnt7b is a physiological regulator of pancreatic progenitor cell growth.
      Genetic deletion of Wnt7b in the developing pancreas leads to pancreatic
      hypoplasia due to reduced proliferation of pancreatic progenitor cells during the
      phase of pancreas development marked by rapid progenitor cell growth. While the
      differentiation potential of pancreatic progenitor cells is unaffected by Wnt7b
      deletion, through a gain-of-function analysis, we find that early pancreatic
      progenitor cells are highly sensitive to Wnt7b expression, but later lose such
      competence. By modulating the level and the temporal windows of Wnt7b expression
      we demonstrate a significant impact on organ growth and morphogenesis
      particularly during the early branching stages of the organ, which negatively
      affects generation of the pro-endocrine (Ngn3(+)/Nkx6.1(+)), and pro-acinar
      (Ptf1A(+)) fields. Consequently, Wnt7b gain-of-function results in failed
      morphogenesis and almost complete abrogation of the differentiation of endocrine
      and acinar cells, leading to cystic epithelial metaplasia expressing ductal
      markers including Sox9, Hnf6 and Hnf1beta. While Wnt7b is expressed exclusively
      in the developing pancreatic epithelium, adjacent mesenchymal cells in the organ
      display a direct trophic response to elevated Wnt7b and increase expression of
      Lef1, cFos and desmin. Of note, in contrast to the pancreatic epithelium, the
      pancreatic mesenchyme remains competent to respond to Wnt7b ligand, at later
      stages in development. We conclude that Wnt7b helps coordinate pancreatic
      development through autocrine, as well as paracrine mechanisms, and as such
      represents a novel bi-modal morphogen ligand. 

PMID- 25576929
TI  - Low-cost and highly efficient DNA biosensor for heavy metal ion using specific
      DNAzyme-modified microplate and portable glucometer-based detection mode.
AB  - A simple and low-cost DNA sensing platform based on Pb(2+)-specific DNAzyme
      modified microplate was successfully developed for highly sensitive monitoring of
      lead ion (Pb(2+), one kind of toxic heavy metal ion) in the environmental samples
      coupling with a portable personal glucometer (PGM)-based detection mode. The
      detection cell was first prepared simply by means of immobilizing the DNAzyme on
      the streptavidin-modified microplate. Gold nanoparticle labeled with single
      stranded DNA and invertase (Enz-AuNP-DNA) was utilized as the signal-transduction
      tag to produce PGM substrate (glucose). Upon addition of lead ion into the
      microplate, the substrate strand of the immobilized DNAzyme was catalytically
      cleaved by target Pb(2+), and the newly generated single-strand DNA in the
      microplate could hybridize again with the single-stranded DNA on the Enz-AuNP
      DNA. Accompanying with the Enz-AuNP-DNA, the carried invertase could convert
      sucrose into glucose. The as-produced glucose could be monitored by using a
      widely accessible PGM for in situ amplified digital readout. Based on Enz-AuNP
      DNA amplification strategy, as low as 1.0 pM Pb(2+) could be detected under the
      optimal conditions. Moreover, the methodology also showed good reproducibility
      and high selectivity toward target Pb(2+) against other metal ions because of
      highly specific Pb(2+)-dependent DNAzyme, and was applicable for monitoring
      Pb(2+) in the naturally contaminated sewage and spiked drinking water samples.

PMID- 25576930
TI  - Molecular mimicry between Mycobacterium leprae proteins (50S ribosomal protein L2
      and Lysyl-tRNA synthetase) and myelin basic protein: a possible mechanism of
      nerve damage in leprosy.
AB  - Autoantibodies against various components of host are known to occur in leprosy.
      Nerve damage is the primary cause of disability associated with leprosy. The aim
      of this study was to detect the level of autoantibodies and lympho-proliferative
      response against myelin basic protein (MBP) in leprosy patients (LPs) and their
      correlation with clinical phenotypes of LPs. Further, probable role of molecular
      mimicry in nerve damage of LPs was investigated. We observed significantly high
      level of anti-MBP antibodies in LPs across the spectrum and a positive
      significant correlation between the level of anti-MBP antibodies and the number
      of nerves involved in LPs. We report here that 4 B cell epitopes of myelin A1 and
      Mycobacterium leprae proteins, 50S ribosomal L2 and lysyl tRNA synthetase are
      cross-reactive. Further, M. leprae sonicated antigen hyperimmunization was
      responsible for induction of autoantibody response in mice which could be
      adoptively transferred to naive mice. For the first time our findings suggest the
      role of molecular mimicry in nerve damage in leprosy. 

PMID- 25576931
TI  - Validation of patient health questionnaire (PHQ) for major depression in Chinese
      outpatients with multiple somatic symptoms: a multicenter cross-sectional study.
AB  - BACKGROUND: Despite the high co-morbidity of depressive symptoms in patients with
      multiple somatic symptoms, the validity of the 9-item Patient Health
      Questionnaire (PHQ-9) has not yet been investigated in Chinese patients with
      multiple somatic symptoms. METHODS: The multicenter cross-sectional study was
      conducted in ten outpatient departments located in four cities in China. The
      psychometric properties of the PHQ-9 were examined by confirmative factor
      analysis (CFA). Criterion validation was undertaken by comparing results with
      depression diagnoses obtained from the Mini International Neuropsychiatric
      Interview (MINI) as the gold standard. RESULTS: Overall, 491 patients were
      recruited of whom 237 had multiple somatic symptoms (SOM+ group, PHQ-15>=10).
      Cronbach's alpha of the PHQ-9 was 0.87, 0.87, and 0.90 for SOM+ patients, SOM-
      patients, and total sample respectively. All items and the total score were
      moderately correlated. The factor models of PHQ-9 tested by CFA yielded similar
      diagnostic performance when compared to sum score estimation. Multi-group
      confirmatory factor analysis based on unidimensional model showed similar
      psychometric properties over the groups with low and high somatic symptom burden.
      The optimal cut-off point to detect depression in Chinese outpatients was 10 for
      PHQ-9 (sensitivity=0.77, specificity=0.76) and 3 for PHQ-2 (sensitivity=0.77,
      specificity=0.74). LIMITATIONS: Potential selection bias and nonresponse bias
      with applied sampling method. CONCLUSIONS: PHQ-9 (cut-off point=10) and PHQ-2
      (cut-off point=3) were reliable and valid to detect major depression in Chinese
      patients with multiple somatic symptoms.

PMID- 25576932
TI  - Dual antibody therapy to harness the innate anti-tumor immune response to enhance
      antibody targeting of tumors.
AB  - Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for
      cancer treatment: therapies focus on enhancing the immune system's innate and
      adaptive anti-tumor response. Early immunotherapeutics have achieved impressive
      clinical outcomes and monoclonal antibodies are now integral to therapeutic
      strategies in a variety of cancers. However, only recently have antibodies
      targeting innate immune cells entered clinical development. Innate immune
      effector cells play important roles in generating and maintaining antitumor
      immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody
      dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for
      tumor eradication. These cytolytic processes are initiated by the detection of a
      tumor-targeting antibody and can be augmented by activating co-stimulatory
      pathways or blocking inhibitory signals on innate immune cells. The combination
      of FDA-approved monoclonal antibodies with innate effector-targeting antibodies
      has demonstrated potent preclinical therapeutic synergy and early-phase
      combinatorial clinical trials are ongoing. 

PMID- 25576933
TI  - A new relation between prevalence and incidence of a chronic disease.
AB  - In 1991 Keiding published a relation between the age-specific prevalence and
      incidence of a chronic disease (in Age-specific incidence and prevalence: a
      statistical perspective. J. Roy. Stat. Soc. A, 154, 371-412). For special cases
      alternative formulations by differential equations were given recently in Brinks
      et al. (2013, Deriving age-specific incidence from prevalence with an ordinary
      differential equation. Statist. Med., 32, 2070-2078) and in Brinks & Landwehr
      (2014, Age- and time-dependent model of the prevalence of non-communicable
      diseases and application to dementia in Germany, Theor. Popul. Biol., 92, 62-68).
      From these works, we generalize formulations and discuss the advantages of the
      novel approach. As an implication, we obtain a new way of estimating the
      incidence rate of a chronic disease from prevalence data. This enables us to
      employ cross-sectional studies where otherwise expensive and lengthy follow-up
      studies are needed. This article illustrates and validates the novel method in a
      simulation study about dementia in Germany.

PMID- 25576934
TI  - Optical properties of two-dimensional zigzag and armchair graphyne nanoribbon
      semiconductor.
AB  - Optical properties of zigzag and armchair graphyne nanoribbon (GNR) sheet were
      investigated. Effect of increasing the width of nanoribbon on optical properties
      and optical band gap in particular was also studied. Calculations were based on
      density functional theory (DFT) and the results showed that these structures were
      semiconductors with the optical band gap of about 1-3.5 eV; this value was higher
      than for the armchair than zigzag structures. With increasing the width of the
      ribbons, optical band gap decreased in both structures and maximum electron
      energy loss spectroscopy (EELS) and dielectric constant increased for the zigzag
      and armchair structures. Moreover, for the armchair structure, maximum optical
      reflectivity versus GNR width was a linear function, while it showed a teeth
      behavior for the zigzag structure.

PMID- 25576935
TI  - Crystal structures, spectroscopic and theoretical study of novel Schiff bases of
      2-(methylthiomethyl)anilines.
AB  - New Schiff bases derived from p-methoxysalicylaldehyde and 2
      (methylthiomethyl)anilines (substituted with methyl, methoxy, nitro) were
      synthesized and characterized by elemental analyses, FT-IR, NMR, electronic
      spectra and quantum chemical calculations. X-ray crystallography of two compounds
      showed the solid structures are stabilized by intramolecular and intermolecular H
      bonds. The effect of OH?N interaction between the phenolic hydrogen and imine
      nitrogen on the proton and carbon NMR shifts, and the role of CH?O and CH?S
      contacts are discussed. The bond lengths and angles, (1)H and (13)C NMR data,
      E(LUMO-HOMO), dipole moments and polarizability of the compounds were predicted
      by density functional theory, DFT (B3LYP/6-31G**) method. The experimental
      geometric parameters and the NMR shifts were compared with the calculated values,
      which gave good correlations. The electronic effects of aryl ring substituents
      (methyl, methoxy and nitro) on the properties of the resulting compounds, such as
      the color, NMR shifts, electronic spectra and the calculated energy band gaps,
      dipole moments and polarizability are discussed. Increase in electron density
      shifted the phenolic proton resonance to lower fields. The methoxy-substituted
      compound has a small dipole moment and subsequent large polarizability value.
      Highest polarity was indicated by the nitro compound which also showed high
      polarizability due to its larger size. The energy gaps obtained from E(LUMO-HOMO)
      calculations suggest these compounds may have applications as organic
      semiconducting materials.

PMID- 25576936
TI  - Ni(II), Pd(II) and Pt(II) complexes of (1H-1,2,4-triazole-3
      ylimino)methyl]naphthalene-2-ol. Structural, spectroscopic, biological,
      cytotoxicity, antioxidant and DNA binding.
AB  - Metal complexes of the general formula [ML(H2O)Cl]nH2O; n=1 for M=Ni and Pt and
      n=2 for M=Pd, L=Schiff base (HL) derived from the condensation of 3-amino-1,2,4
      triazole and 2-hydroxy-1-naphthaldehyde, were prepared. The synthesized ligand
      and its metal complexes were characterized on the basis of elemental analyses,
      spectral and magnetic studies as well as thermal analysis. The IR spectra
      revealed that the ligand is coordinated to the metal ions in bidentate manner via
      the N-atom of the azomethine group and the phenolic OH group. Square planar
      geometry was proposed for Pd(II) and Pt(II) complexes and tetrahedral for Ni(II)
      complex. The ligand and its metal complexes were screened against the sensitive
      organisms Escherichia coli as Gram-negative bacteria, Staphylococcus aureus as
      Gram-positive bacteria, Aspergillus flavus and Candida albicans as fungi.
      Moreover, the anticancer activity of the ligand and its metal complexes was
      evaluated in liver carcinoma (HEPG2) cell line. The results obtained indicated
      that the Schiff base ligand is more effective than its metal complexes towards
      the tested cell line. Ni(II), Pd(II) and Pt(II) complexes as well as the free
      Schiff base ligand were tested for their antioxidant activities. The DNA-binding
      properties of the studied complexes have been investigated by electronic
      absorption and viscosity measurements. 

PMID- 25576937
TI  - Colorimetric detection of anions in aqueous media using N-monosubstituted
      diaminomaleonitrile-based azo-azomethine receptors: real-life applications.
AB  - New N-monosubstituted diaminomaleonitrile-based azo-azomethine dyes have been
      synthesized in order to develop colorimetric sensors for detection of
      biologically important anions in aqueous media. Importantly, the reported sensor
      decorated with strong electron-withdrawing group can detect inorganic fluoride in
      water even at 0.037 ppm level, which is lower than WHO permissible level (below 1
      ppm). Successfully, the prepared dyes were used for qualitative and quantitative
      detection of inorganic fluoride in toothpaste and mouthwash. The anion
      recognition mechanism was also investigated by detailed UV-Vis and (1)H NMR
      experiments. The detailed (1)H NMR experiments corroborated that anion
      recognition is based on the deprotonation phenomenon.

PMID- 25576938
TI  - Spectroscopic investigation (FT-IR and FT-Raman), vibrational assignments, HOMO
      LUMO, NBO, MEP analysis and molecular docking study of 2-[(4
      chlorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-(phenylsulfanyl)-pyrimidine-5
      carbonitrile, a potential chemotherapeutic agent.
AB  - Vibrational spectral analysis of 2-[(4-chlorobenzyl)sulfanyl]-4-(2-methylpropyl)
      6-(phenylsulfanyl)-pyrimidine-5-carbonitrile was carried out using FT-IR and FT
      Raman spectroscopic techniques. The equilibrium geometry and vibrational wave
      numbers have been computed using density functional B3LYP method with 6
      311++G(d,p)(5D,7F) as basis set. Stability of the molecule arising from hyper
      conjugative interactions, charge delocalization has been analyzed using NBO
      analysis. The nonlinear optical behavior of the title compound is also
      theoretically predicted. From the MEP, it is evident that the negative charge
      covers the C=N group and the positive region is over the phenyl and the
      pyrimidine rings. From the potential energy scan it is clear that the lone pairs
      of the sulfur atom prefer to point away from the pyrimidine ring and the C=N
      group resulting with two possible minimum conformations at the N4C8S1C25 angle
      equal nearly 0 degrees  or 150 degrees . Molecular docking results suggest that
      the compound might exhibit inhibitory activity against GPb and may act as
      potential anti-diabetic compound.

PMID- 25576939
TI  - Enhancement of nonlinear optical (NLO) properties of indigo through modification
      of auxiliary donor, donor and acceptor.
AB  - In this study, indigo based dyes with high non-linear optical response have been
      investigated. Density functional theory (DFT) was used to study non-linear
      optical properties of indigo and newly designed dyes (IM-Dye-0, IM-Dye-1, IM-Dye
      2 and IM-Dye-3). The time dependant density functional theory (TDDFT) was used to
      calculate the excitation energies. The HOMO-LUMO energy gaps of newly designed
      dyes were smaller as compare with indigo dye. Absorption maxima of newly designed
      dyes strongly red shifted as compare with indigo dye. High non-linear optical
      (NLO) response of newly designed dyes revealed that these materials would be
      excellent for NLO applications. This theoretical approach of designing will pave
      the way for experimentalists to synthesize high response NLO compound. 

PMID- 25576940
TI  - Synthesis and characterization of chromium(III) Schiff base complexes:
      antimicrobial activity and its electrocatalytic sensing ability of catechol.
AB  - A series of acyclic Schiff base chromium(III) complexes were synthesized with the
      aid of microwave irradiation method. The complexes were characterized on the
      basis of elemental analysis, spectral analysis such as UV-Visible, Fourier
      transform infrared (FT-IR), nuclear magnetic resonance (NMR), electron
      paramagnetic resonance (EPR) spectroscopies and electrospray ionization (ESI)
      mass spectrometry. Electrochemical analysis of the complexes indicates the
      presence of chromium ion in +3 oxidation state. Cr (III) ion is stabilized by the
      tetradentate Schiff base ligand through its nitrogen and phenolic oxygen. From
      the spectral studies it is understood that the synthesized chromium(III)
      complexes exhibits octahedral geometry. Antimicrobial activity of chromium
      complexes was investigated towards the Gram positive and Gram negative bacteria.
      In the present work, an attempt was made to fabricate a new kind of modified
      electrode based on chromium Schiff base complexes for the detection of catechol
      at nanomolar level. 

PMID- 25576941
TI  - Synthesis, crystal structures, luminescence and catalytic properties of two d10
      metal coordination polymers constructed from mixed ligands.
AB  - Two new coordination polymers [Cd(bmb)(hmph)]n (1), {[Ag(bmb)].H2btc}n (2)
      (bmb=1,4-bis(2-methylbenzimidazol-1-ylmethyl)benzene, H2hmph=homophthalic acid,
      H3btc=1,3,5-benzenetetracarboxylic acid) were synthesized under hydrothermal
      conditions and characterized by single-crystal X-ray diffraction methods, IR
      spectroscopy, TGA, XRPD and elemental analysis. Complex 1 features a 3D threefold
      interpenetrating dia array with a 4-connected 6(6) topology. Complex 2 shows a 1D
      helix chain structure connected by L1 ligands, which is finally extended into a
      rarely 2D 4L2 supramolecular network via C-H?O hydrogen bond interactions. In
      addition, the luminescence and catalytic properties of the two complexes for the
      degradation of the methyl orange azo dye in a Fenton-like process were presented.
      The degradation efficiency of the methyl orange azo dye for 1 and 2 are 56% and
      96%, respectively. 

PMID- 25576942
TI  - Application of Savitzky-Golay differentiation filters and Fourier functions to
      simultaneous determination of cefepime and the co-administered drug,
      levofloxacin, in spiked human plasma.
AB  - The present work is concerned with simultaneous determination of cefepime (CEF)
      and the co-administered drug, levofloxacin (LEV), in spiked human plasma by
      applying a new approach, Savitzky-Golay differentiation filters, and combined
      trigonometric Fourier functions to their ratio spectra. The different parameters
      associated with the calculation of Savitzky-Golay and Fourier coefficients were
      optimized. The proposed methods were validated and applied for determination of
      the two drugs in laboratory prepared mixtures and spiked human plasma. The
      results were statistically compared with reported HPLC methods and were found
      accurate and precise. 

PMID- 25576943
TI  - Vibrational spectra of guaiacylglycerol-beta-guaiacyl ether: experiment and
      theory.
AB  - As an important inter-unit of lignin, guaiacylglycerol-beta-guaiacyl (GG) ether
      has been synthesized, and characterized using terahertz time-domain spectroscopy
      in the frequency range of 5-85 cm(-1). Seven absorption peaks have been observed.
      Among these peaks, the 49.8 cm(-1) and 57.6 cm(-1) vibrations are propose to be
      characteristic absorption peaks of GG ether. Raman spectra were also measured in
      the range of 50-3500 cm(-1). The vibrations of the two lowest energy forms, i.e.,
      erythro 1r4s and threo 1s4s, were calculated using density functional theory at
      the B3LYP/6-311G** level and assigned according to potential energy distribution.
      In addition, the contents of erythro and threo forms in GG sample could be
      estimated by comparing the waveform similarities between theoretical and observed
      curves in the 33.0-80.0 cm(-1) range. Results showed that the observed curve of
      GG sample is a combination of erythro 1s4r and threo 1s4s. The four absorption
      vibrations below 33.0 cm(-1) could be assigned to phonon, inter-molecular modes
      and/or hydrogen bond vibrations. Terahertz spectra and Raman spectra, together
      with theoretical calculations, could be powerful methods for predicting contents
      of different isomers in sample.

PMID- 25576944
TI  - Novel A3B-type tert-butyl-substituted tribenzodiazepinoporphyrazine: synthesis,
      spectral properties and DFT study.
AB  - Novel A3B-type 8(9),13(14),18(19)-tri-tert-butyl-2(5),4(7)-bis(4-tert
      butylphenyl)tribenzo[g,l,q]-6H-1,4-diazepino[2,3-b]porphyrazine, which has high
      solubility in organic solvents, was obtained by template co-condensation of 2,3
      dicyano-5,7-bis(4-tert-butylphenyl)-6H-1,4-diazepine and 4-tert
      butylphthalonitrile. It was characterized by UV/Vis, (1)H, (13)C NMR
      spectroscopy, and MALDI-TOF/TOF mass spectrometry. We have demonstrated for the
      first time using fluorescence spectroscopy measurements and quantum-chemical
      calculations that the complicated UV/Vis spectrum of A3B-type
      tribenzodiazepinoporphyrazine is due to the formation of stable H-type
      aggregates. 

PMID- 25576945
TI  - Spectrophotometric determination of trace carbaryl in water and grain samples by
      inhibition of the rhodamine-B oxidation.
AB  - A novel, sensitive, selective and simple kinetic spectrophotometric method has
      been developed for determination of trace levels of carbaryl based on its
      inhibitory effect on the oxidation of rhodamine-B by chlorine and bromine
      released from reaction of potassium bromate with hydrochloric acid in micellar
      medium. A linear relationship was observed between the inhibitory effect and the
      concentration of the compound. The absorbance was monitored at the maximum
      wavelength of 555 nm. The effect of different parameters such as pH, temperature
      and concentration of rhodamine-B, potassium bromate and surfactant on the
      reaction were investigated and optimum conditions were established. Under the
      selected experimental conditions, carbaryl was determined in the range of 0.04
      0.4 MUg mL(-1). Sandell's sensitivity and molar absorptivity were found to be
      0.00055 MUg cm(-2) and 3.658*10(5) L mol(-1) cm(-1) respectively. The proposed
      method was applied satisfactorily for the determination of carbaryl in water and
      different grain samples. The results were compared with those obtained by
      reference method and were found to be in agreement.

PMID- 25576946
TI  - Synthesis, molecular docking and biological evaluation of novel 6-(4-(4
      aminophenylsulfonyl)phenylamino)-5H-benzo[a]phenothiazin-5-one derivatives.
AB  - A novel series of 6-(4-(4-aminophenylsulfonyl)phenylamino)-5H
      benzo[a]phenothiazin-5-one derivatives have been synthesized and examined for
      their in vitro antibacterial activity against a panel of Gram-positive and Gram
      negative bacteria. Among these, N-(4-(4-(5-oxo-5H-benzo[a]phenothiazin-6
      ylamino)phenylsulfonyl)phenyl)-3,5-bis(trifluoromethyl)benzamide (3n) (0.4
      MUg/mL) and 4-ethyl-N-(4-(4-(5-oxo-5H-benzo[a]phenothiazin-6
      ylamino)phenylsulfonyl)phenyl)benzamide (3l) (0.6 MUg/mL) systems exhibited a
      potent inhibitory activity against Gram-positive organism Bacillus subtilis, when
      compare to the other synthesized compounds. Sparfloxacin (9.76 MUg/mL),
      Norfloxacin (no activity) were employed as the standard drugs. An evaluation of
      the cytotoxicity of the title compounds (1, 2, 3a-n) revealed that they displayed
      low toxicity (26-115 mg/L) against cervical cancer cell line (SiHa). The results
      of these studies suggest that, phenothiazin-5-one derivatives are interesting
      binding agents for the development of new Gram-positive and Gram-negative
      antibacterial agents. To understand the interactions with protein receptors,
      docking simulation was done with crystal structures of B.subtilis (YmaH) and
      histone deacetylase (HDAC8) to determine the probable binding conformation.

PMID- 25576947
TI  - Raman and terahertz spectroscopical investigation of cocrystal formation process
      of piracetam and 3-hydroxybenzoic acid.
AB  - Cocrystallization can improve physical and chemical properties of active
      pharmaceutical ingredient, and this feature has great potential in pharmaceutical
      development. In this study, the cocrystal of piracetam and 3-hydroxybenzoic acid
      under grinding condition has been characterized by Raman and terahertz
      spectroscopical techniques. The major vibrational modes of individual starting
      components and cocrystal are obtained and assigned. Spectral results show that
      the vibrational modes of the cocrystal are different from those of the
      corresponding parent materials. The dynamic process of such pharmaceutical
      cocrystal formation has also been monitored directly with Raman and THz spectra.
      The formation rate is pretty fast in first several 20 min grinding time, and then
      it becomes slow. After ~35 min, such process has been almost completed. These
      results offer us the unique means and benchmark for characterizing the cocrystal
      conformation from molecule-level and also provide us rich information about the
      reaction dynamic during cocrystal formation process in pharmaceutical fields.

PMID- 25576948
TI  - Conformational study of some 4'-substituted 2-(phenylselanyl)-2-(ethylsulfanyl)
      acetophenones.
AB  - The conformational analysis of some 4'-substituted 2-(phenylselanyl)-2
      (ethylsulfanyl)-acetophenones bearing the substituents NO2 (1), Br (2), H (3), Me
      (4) and OMe (5) was performed by nu(CO) IR analysis, B3LYP/6-31+G(d,p) and single
      point polarisable continuum model (PCM) calculations, along with NBO analysis for
      1, 3 and 5. Calculations for 1-5 indicate the existence of three stable
      conformations, c1, c2 and c3, whose stability depends on the balance between
      electrostatic and orbital interactions that are strictly related to the
      geometrical arrangement. The comparison between the experimental IR spectra in
      solution and the computed data in gas phase for 1-5 allows the c1 conformer to be
      assigned to the less intense component at higher frequency of the carbonyl
      doublet and both the c2 and c3 ones to the more intense lower frequency
      component. The sum of the calculated molar fraction of c2 and c3 conformers
      decreases from 95% to 63% on going from 1 to 5 (in gas phase), and this trend
      compares well with the PCM calculations and the IR experimental data for the
      majority of the solvents for all compounds 1-5. The NBO analysis for 1, 3 and 5
      shows that the sum of the relevant orbital delocalization energies for the c1, c2
      and c3 conformers is almost constant and does not match the computed stability
      order. The lowest stability of the c1 conformer for 1-3 can be related to the
      small value of the alpha dihedral angle that enables a strong electrostatic
      destabilizing repulsion between the O(CO)(delta-)...S(delta-) atoms. The relative
      stability of the c1 conformer increases for 4 and 5 as the alpha dihedral angle
      enlarges and the repulsion is minimized. Moreover, the strong repulsive field
      effect between the C(delta+)=O(delta-) and C(delta+)-S(delta-) dipoles exerted to
      a greater extent on the c1 conformers of 1-3 with respect to 4 and 5, causes a
      major increase of the corresponding C=O bond orders and related carbonyl
      frequencies. For the c2 conformer, the electrostatic destabilizing repulsion
      between the O(delta-)...Se(delta-) atoms is weaker than that involving the
      O(delta-)...S(delta-) atoms in the c1 conformer and therefore has negligible
      effects on the conformer stability that is mainly determined by the sum of the
      orbital interactions. The c3 conformer has the shortest S(delta-)...Se(delta-)
      contact for all compounds and thus the related electrostatic repulsion seems to
      be the most important factor that affects its stability. In conclusion, the
      computed order of stability of the three conformers for 1-5 depends on the
      electrostatic repulsions between close charged atoms rather than on the sum of
      the orbital delocalization energies that are quite similar for all the
      conformers.

PMID- 25576949
TI  - Combined spectroscopic and DFT studies on 6-bromo-4-chloro-3-formyl coumarin.
AB  - The FTIR and FT-Raman spectra of 6-bromo-4-chloro-3-formyl coumarin (6B4C3FC)
      have been recorded in the region 4000-400 and 4000-100 cm(-1), respectively. The
      optimized geometry, frequency and intensity of the vibrational bands were
      obtained by the density functional theory (DFT) using 6-31G(d,p) basis set. The
      harmonic vibrational frequencies were scaled and compared with experimental
      values. The observed and the calculated frequencies were found to be in good
      agreement. The UV-Visible spectrum was also recorded and compared with the
      theoretical values. The calculated HOMO and LUMO energies show that charge
      transfer occurs within molecule. The first order hyperpolarizability (beta0) of
      6B4C3FC is 21 times greater than that of urea. Stability of the molecule arising
      from hyperconjugative interactions, charge delocalization have been analyzed
      using natural bond orbital (NBO) analysis. Information about the charge density
      distribution of the molecule and its chemical reactivity has been obtained by
      mapping molecular electrostatic potential surface. In addition, the non-linear
      optical properties were discussed from the dipole moment values and the
      excitation wavelength in the UV-Visible region.

PMID- 25576950
TI  - Agricultural waste as a source for the production of silica nanoparticles.
AB  - The major interest of the paper deals with the extraction of silica from four
      natural sources such as rice husk, bamboo leaves, sugarcane bagasse and groundnut
      shell. These waste materials in large quantities can create a serious
      environmental problem. Hence, there is a need to adopt proper strategy to reduce
      the waste. In the present investigation, all the waste materials are subjected to
      moisture removal in a hot plate and sintered at 900 degrees C for 7 h. The
      sintered powder was treated with 1 M NaOH to form sodium silicate and then with
      6M H2SO4 to precipitate silica. The prepared silica powders were characterized by
      FT-IR, XRD and SEM-EDAX analysis. The silica recovered from different sources was
      found to vary between 52% and 78%. Magnesium substituted silica was formed from
      the groundnut waste and further treatment is required to precipitate silica.

PMID- 25576951
TI  - Energy drink consumption and later alcohol use among early adolescents.
AB  - INTRODUCTION: Little is known about the association between energy drink and
      other substance use in early adolescence despite the fact that the consumption of
      energy drinks during this developmental period is becoming increasingly common.
      The aim of this study was to examine concurrent and longitudinal associations
      between energy drink and alcohol use among middle school students. In addition,
      sensation seeking and parental monitoring were examined as factors that could
      potentially explain any associations found. METHODS: A sample of 144 youth
      participating in the Camden Youth Development Study was utilized. Self-report
      questionnaire data was collected over a 16-month period. RESULTS: Frequency of
      energy drink use at the initial assessment predicted increases in frequency of
      alcohol use 16 months later (adjusting for initial frequency of alcohol use).
      Levels of parental monitoring partially accounted for this association; in
      contrast, there was no evidence that sensation seeking was related to this
      association. CONCLUSION: Youth who consume energy drinks in early adolescence are
      at risk for alcohol use later; this may be partially related to low levels of
      parental monitoring being associated with the consumption of both substances.
      Future research is needed to further explain this association; this may lead to
      opportunities for early intervention for youth at high risk for alcohol use.

PMID- 25576952
TI  - An experimental investigation of the functional relationship between social
      phobia and cigarette smoking.
AB  - INTRODUCTION: Individuals with social phobia (SP) represent a large group with
      elevated rates of cigarette smoking and cessation rates lower than that of
      individuals without psychopathology. For individuals with SP, cigarette smoking
      may be used to reduce social anxiety in anticipation of and during social
      situations. However, no study to date has experimentally examined this
      association. The aim of the current study was to experimentally examine the
      relationship between cigarette smoking and SP as a function of induced social
      stress. METHOD: We recruited daily smokers ages 18-21 who scored in either a
      clinical or normative range on the Social Interaction Anxiety Scale (SIAS).
      Participants included 54 smokers (42.6% female, 77.8% White, age
      M(SD)=19.65(1.18), CPSD M(SD)=7.67(4.36), 46.30% high SP) who attended two
      sessions: one social stress session and one neutral session. RESULTS: Results
      indicated that high SP smokers experienced significant decreases in negative
      affect (NA) following smoking a cigarette when experiencing social stress. This
      effect was specific to high SP smokers under social stress and was not observed
      among individuals' average in SP or when examining changes in positive affect.
      CONCLUSIONS: For individuals with SP, cigarette smoking may be maintained due to
      changes in NA associated with smoking specifically in the context of social
      stress. These results speak to the importance of targeted cessation interventions
      that address the nature of smoking for individuals with SP.

PMID- 25576953
TI  - Construction of a random circular permutation library using an engineered
      transposon.
AB  - Circular permutation is an important protein engineering tool used to create
      sequence diversity of a protein by changing its linear order of amino acid
      sequence. Circular permutation has proven to be effective in the evolution of
      proteins for desired properties while maintaining similar three-dimensional
      structures. Due to the lack of a robust design principle guiding the selection of
      new termini, construction of a combinatorial library is much preferred for
      comprehensive evaluation of circular permutation. Unfortunately, the conventional
      methods used to create random circular permutation libraries cause significant
      sequence modification at new termini of circular permutants. In addition, these
      methods impose additional limitations by requiring either relatively inefficient
      blunt-end ligation during library construction or redesign of transposons for
      tailored expression of circular permutants. In this study, we present the
      development of an engineered transposon for facile construction of random
      circular permutation libraries. We provide evidence that minimal modification at
      the new termini of the random circular permutants is possible with our engineered
      transposon. In addition, our method enables the use of sticky-end ligation during
      library construction and provides external tunability for expression of random
      circular permutants. 

PMID- 25576954
TI  - ZnO-CuxO/polypyrrole nanocomposite modified electrode for simultaneous
      determination of ascorbic acid, dopamine, and uric acid.
AB  - Novel zinc oxide (ZnO) nanosheets and copper oxide (CuxO, CuO, and Cu2O)
      decorated polypyrrole (PPy) nanofibers (ZnO-CuxO-PPy) have been successfully
      fabricated for the simultaneous determination of ascorbic acid (AA), dopamine
      (DA), and uric acid (UA). The morphology and structure of ZnO-CuxO-PPy
      nanocomposites were characterized by scanning electron microscopy (SEM), X-ray
      diffraction (XRD), and Raman spectroscopy. Compared with the bare glassy carbon
      electrode (GCE), PPy/GCE, CuxO-PPy/GCE, and ZnO-PPy/GCE, ZnO-CuxO-PPy/GCE
      exhibits much higher electrocatalytic activities toward the oxidation of AA, DA,
      and UA with increasing peak currents and decreasing oxidation overpotentials.
      Cyclic voltammetry (CV) results show that AA, DA, and UA could be detected
      selectively and sensitively at ZnO-CuxO-PPy/GCE with peak-to-peak separation of
      150 and 154 mV for AA-DA and DA-UA, respectively. The calibration curves for AA,
      DA, and UA were obtained in the ranges of 0.2 to 1.0 mM, 0.1 to 130.0 MUM, and
      0.5 to 70.0 MUM, respectively. The lowest detection limits (signal/noise=3) were
      25.0, 0.04, and 0.2 MUM for AA, DA, and UA, respectively. With good selectivity
      and sensitivity, the current method was applied to the determination of DA in
      injectable medicine and UA in urine samples.

PMID- 25576955
TI  - Sequence variants in the bovine silent information regulator 6, their linkage and
      their associations with body measurements and carcass quality traits in Qinchuan
      cattle.
AB  - Silent information regulator 6 (SIRT6) belongs to the family of class III
      nicotinamide adenine dinucleotide (NAD)-dependent deacetylase and plays an
      essential role in DNA repair and metabolism. This study was conducted to detect
      potential polymorphisms of the bovine SIRT6 gene and explore their relationships
      with body measurement and carcass quality in Qinchuan cattle. Four sequence
      variants (SVs) were identified in intron 6, exon 7, exon 9, and 3' UTR, via
      sequencing technology conducted in 468 individual Qinchuan cattle. Eleven
      different haplotypes were identified, of which two major haplotypes had a
      frequency of 45.7% (-CACT-) and 14.8% (-CGTC-). Three SVs (SV2, SV3 and SV4) were
      significantly associated with some of the body measurements and carcass quality
      traits (P<0.05 or P<0.01), and the H2H7 (CC-GA-TT-TC) diplotype had better
      performance than other combinations. Our results suggest that some polymorphisms
      in SIRT6 are associated with production traits and may be used as candidates for
      marker-assisted selection (MAS) and management in beef cattle breeding programs.

PMID- 25576956
TI  - Comparative profiling of gene expression in Camellia sinensis L. cultivar
      AnJiBaiCha leaves during periodic albinism.
AB  - The AnJiBaiCha albino mutant tea cultivar has a reversible albino phenotype at
      low temperatures. Albino AnJiBaiCha leaves contain high levels of amino acids,
      which are important components affecting the quality of tea as a beverage. To
      examine the molecular mechanism of albinism and amino acid enrichment in
      AnJiBaiCha, we used the amplified fragment length polymorphism (cDNA-AFLP)
      technique to isolate genes that are differentially expressed during periodic
      albinism in AnJiBaiCha. A total of 127 transcript-derived fragments (TDFs) were
      successfully sequenced; among those, 60 TDFs showed high similarity to sequences
      with known functions, but 67 TDFs were not similar to any known genes. The
      identified transcripts include transcription factors, ubiquitination-related
      genes, chloroplast biogenesis genes, signal transduction genes, stress-related
      genes, cell cycle genes, and carbohydrate and energy metabolism genes. To
      validate the cDNA-AFLP results, quantitative real-time PCR was used to confirm
      the differential expression of six of the identified genes. The cDNA-AFLP and
      quantitative real-time PCR results correlated well, indicating that the cDNA-AFLP
      results are reliable. This study provides insights into the molecular mechanisms
      by which periodic albinism and amino acid accumulation take place in AnJiBaiCha. 

PMID- 25576957
TI  - Toxicological assessment of Ashitaba Chalcone.
AB  - The plant Angelica keiskei contains two main physiologically active flavonoid
      chalcones, 4-hydroxyderricin and xanthoangelol. Known as ashitaba in Japan,
      powder from the sap is widely consumed for its medicinal properties in Asia as a
      dietary supplement. Limited previously reported mammalian studies were without
      evidence of toxicity. GLP studies reported here, including a bacterial reverse
      mutation assay, a chromosome aberration assay, and an in vivo micronucleus assay
      are negative for genotoxicity. A GLP- compliant 90-day repeated oral gavage study
      of ashitaba yellow sap powder containing 8.45% chalcones in Sprague Dawley rats
      resulted in expected known physiological effects on coagulation parameters and
      plasma lipids at 300 and 1000 mg/kg/day. Ashitaba-related pathology included a
      dose-related male rat-specific alpha 2-urinary globulin nephropathy at 100, 300,
      and 1000 mg/kg/day and jejunal lymphangiectasia in both sexes at 1000 mg/kg/day.
      All other study parameters and histopathological changes were incidental or not
      of toxicological concern. Based on these studies ashitaba chalcone powder is not
      genotoxic with a NOAEL of 300 mg/kg in male and female rats. 

PMID- 25576958
TI  - A case of intra-abdominal hemorrhage secondary to peliosis hepatis.
AB  - INTRODUCTION: peliosis hepatis (PH) is a rare vascular condition of the liver
      characterized by the presence of cystic blood filled cavities distributed
      randomly throughout the liver parenchyma Tsokos and co-workers [1-6]. Peliosis is
      most commonly found in the liver but can also involve the spleen, bone marrow,
      lungs, and abdominal lymph nodes Tsokos and Erbersdobler [1]. PRESENTATION OF
      CASE: We report a case of peliosis hepatis diagnosed post laparotomy. She
      required a re-look laparotomy with removal of packs peritoneal lavage, placement
      of intraseed and subhepatic drain. The patient was discharged after an 11-day
      recovery period. CONCLUSION: We examine the literature and subsequently discuss
      the etiology and management of peliosis. Peliosis is a rare vascular condition of
      the liver characterized by the presence of cystic blood filled cavities. Causes
      are associated with a number of conditions, however, etiology is largely unknown.
      Management is overwhelmingly conservative except in a handful of cases.

PMID- 25576959
TI  - Small bowell perforation and mesentery injury after an unusual blunt abdominal
      trauma-Case report.
AB  - INTRODUCTION: In blunt abdominal trauma, lesions of the small bowell and
      mesentery are often underdiagnosed; although unusual, they represent the third
      most injured organ, with increasing morbidity and mortality. PRESENTATION OF
      CASE: The authors present the case of a 68 years old male, admitted to the
      emergency department after being hit by a bale of straw, weighing around 300kg,
      in the abdomen. After successful ressuscitation, a CT scan was performed,
      suggesting hemoperitoneum because of vascular lesion of the right colon bleeding.
      An exploratory laparotomy was performed, confirming the presence of blood in the
      abdominal cavity and identifying jejunal perforation, an apparently innocent
      hematoma of the small bowel mesentery (beside the bowel wall) distally to the
      first lesion and a laceration of the sigmoid serosa; a segmental jejunal
      resection and suture of the colon serosa were performed. In the early post
      operative period, an enteric discharge was noticed, mandating surgical
      reexploration; a previously unnoticed bowel perforation, in the mesenteric border
      where the hematoma was identified, justified an additional enterectomy, after
      what the patients recovery progressed uneventfully. DISCUSSION: In this case, a
      sudden increase in abdominal pressure could explain that missed rupture of the
      mesenteric border of the jejunum, also causing the mesenteric hematoma, or, in
      spite of that, a state of low perfusion could have lead to total wall ischemia of
      an already irrigation compromised segment. Only noted after surgical exploration,
      despite prior evaluation with a computed tomography. Small bowell and mesenteric
      injuries are potentially missed due to decreased exploratory laparotomies for
      blunt abdominal trauma. CONCLUSION: Although uncommon, small bowel and mesenteric
      injuries are associated with high morbidity and mortality. High clinical
      suspicion is essential for an early diagnosis.

PMID- 25576960
TI  - Leiomyosarcoma of the mesentry, a rare mesentric tumour.
AB  - Leiomyosarcoma is extremely rare with a reported incidence of 1:350,000. So
      accurate preoperative diagnosis of mesenteric soft tissue tumor is generally
      difficult. Leiomyosarcoma is a malignant tumour arising from smoothcell lineage.
      Mesenteric leiomyosarcoma occurs most commonly in middle-aged individuals. We
      describe a case of leiomyosarcoma arising from the ileal mesentery in a 33 year
      old male patient. The diagnosis was based on histopathologic evaluation using
      immunohistochemical staining. 

PMID- 25576961
TI  - Degloved foot sole successfully reconstructed with split thickness skin grafts.
AB  - INTRODUCTION: The current opinion is that split thickness skin grafts are not
      suitable to reconstruct a degloved foot sole. The tissue is too fragile to carry
      full bodyweight; and therefore, stress lesions frequently occur. The treatment of
      choice is the reuse of the avulsed skin whenever possible, or else the use of a
      full thickness fascio-cutaneus flap. PRESENTATION OF THE CASE: A young male
      sustained a crush injury to his right foot with deglovement of the plantar
      surface and part of the dorsum. DISCUSSION: Split thickness skin grafts are not
      suitable for full weight bearing, but in special circumstances, certain patients,
      a lot of time and patience, early mobilization and gradual increasing partial
      weight bearing it is worthwhile to try. To toughen the foot sole pressure
      distribution is necessary and can be reached in several ways, soft and springy
      materials of the inlay, but also socks, orthopedic shoes, casting, orthotics or
      walking aids. CONCLUSION: This case-report illustrates that the reconstruction of
      a degloved foot sole with split-thickness skin grafts can be successful; a
      silicon inner sole was used to prevent stress lesions.

PMID- 25576962
TI  - Boundary objects in complementary and alternative medicine: acupuncture vs.
      Christian Science.
AB  - Nearly four in ten American use complementary or alternative medicine (CAM) each
      year. Even with a large number of patients, CAM practitioners face scrutiny from
      physicians and biomedical researchers who, in an era of evidence-based medicine,
      argue there is little evidence to support CAM treatments. Examining how CAM has
      or has not been integrated into American health care is crucial in understanding
      the contemporary boundaries of healthcare systems. An analytical tool from
      science and technology studies, boundary objects, can help scholars of medicine
      understand which practices become integrated into these systems. Using a
      comparative analysis based on archival and interview data, this paper examines
      the use of boundary objects in two alternative medical practices - acupuncture
      and Christian Science. While boundary objects alone cannot explain what health
      practices succeed or fail, juxtaposing the use of boundary objects by different
      CAM groups identifies the work boundary objects do to facilitate integration and
      the conditions under which they "work." I find that acupuncturists' use of
      sterile needles as a boundary objects assists in their effective integration into
      U.S. healthcare because needles are both a symbol of biomedical prowess and a
      potentially unsafe device requiring regulation. Christian Scientists' use of the
      placebo effect as a boundary object has not succeeded because they fail to
      acknowledge the different contextual definitions of the placebo effect in
      biomedical communities. This comparative analysis highlights how context affects
      which boundary objects "work" for CAM practices and theorizes why alternative
      health practices succeed or fail to become integrated into healthcare systems. 

PMID- 25576963
TI  - Alterations in brain neurotrophic and glial factors following early age chronic
      methylphenidate and cocaine administration.
AB  - Attention deficit hyperactivity disorder (ADHD) overdiagnosis and a
      pharmacological attempt to increase cognitive performance, are the major causes
      for the frequent (ab)use of psychostimulants in non-ADHD individuals.
      Methylphenidate is a non-addictive psychostimulant, although its mode of action
      resembles that of cocaine, a well-known addictive and abused drug. Neuronal- and
      glial-derived growth factors play a major role in the development, maintenance
      and survival of neurons in the central nervous system. We hypothesized that
      methylphenidate and cocaine treatment affect the expression of such growth
      factors. Beginning on postnatal day (PND) 14, male Sprague Dawley rats were
      treated chronically with either cocaine or methylphenidate. The rats were
      examined behaviorally and biochemically at several time points (PND 35, 56, 70
      and 90). On PND 56, rats treated with cocaine or methylphenidate from PND 14
      through PND 35 exhibited increased hippocampal glial-cell derived neurotrophic
      factor (GDNF) mRNA levels, after 21 withdrawal days, compared to the saline
      treated rats. We found a significant association between cocaine and
      methylphenidate treatments and age progression in the prefrontal protein
      expression of brain derived neurotrophic factor (BDNF). Neither treatments
      affected the behavioral parameters, although acute cocaine administration was
      associated with increased locomotor activity. It is possible that the increased
      hippocampal GDNF mRNA levels, may be relevant to the reduced rate of drug seeking
      behavior in ADHD adolescence that were maintained from childhood on
      methylphenidate. BDNF protein level increase with age, as well as following
      stimulant treatments at early age may be relevant to the neurobiology and
      pharmacotherapy of ADHD. 

PMID- 25576964
TI  - Reduced processing of alcohol cues predicts abstinence in recently detoxified
      alcoholic patients in a three-month follow up period: an ERP study.
AB  - One of the major challenges in alcohol dependence is relapse prevention, as rates
      of relapse following detoxification are high. Drug-related motivational processes
      may represent key mechanisms in alcoholic relapse. In the present study, event
      related potentials (ERPs) were recorded during a visual oddball task administered
      to 29 controls (11 females) and 39 patients (9 females). Deviant stimuli were
      related or unrelated to alcohol. For patients, the task was administered
      following a 3-week detoxification course. Of these, 19 relapsed during the three
      months follow-up period. The P3, an ERP component associated with activation of
      arousal systems in the brain and motivational engagement, was examined with the
      aim to link the fluctuation of its amplitude in response to alcohol versus non
      alcohol cues to the observed relapse rate. Results showed that compared to
      relapsers, abstainers presented with a decreased P3 amplitude for alcohol related
      compared to non-alcohol related pictures (p=.009). Microstate analysis and
      sLORETA topography showed that activation for both types of deviant cues in
      abstainers originated from the inferior and medial temporal gyrus and the uncus,
      regions implicated in detection of target stimuli in oddball tasks and of
      biologically relevant stimuli. Through hierarchical regression, it was found that
      the P3 amplitude difference between alcohol and non-alcohol related cues was the
      best predictor of relapse vulnerability (p=.013). Therefore, it seems that a
      devaluation of the motivational significance of stimuli related to alcohol,
      measurable through electrophysiology, could protect from a relapse within three
      months following detoxification in alcohol-dependent patients. 

PMID- 25576965
TI  - NR2B antagonist CP-101,606 inhibits NR2B phosphorylation at tyrosine-1472 and its
      interactions with Fyn in levodopa-induced dyskinesia rat model.
AB  - The augmented tyrosine phosphorylation of NR2B subunit of N-methyl-d-aspartate
      receptors (NMDAR) dependent on Fyn kinase has been associated with levodopa (l
      dopa)-induced dyskinesia (LID). CP-101,606, one selective NR2B subunit
      antagonist, can improve dyskinesia. Yet, the accurate action mechanism is less
      well understood. In the present study, the evidences were investigated. Valid 6
      hydroxydopamine-lesioned parkinsonian rats were treated with l-dopa
      intraperitoneally for 22 days to induce LID rat model. On day 23, rats received
      either CP-101,606 (0.5mg/kg) or vehicle with each l-dopa dose. On the day of 1,
      8, 15, 22, and 23 during l-dopa treatment, we determined abnormal involuntary
      movements (AIMs) in rats. The levels of NR2B phosphorylation at tyrosine-1472
      (pNR2B-Tyr1472) and interactions of NR2B with Fyn in LID rat model were detected
      by immunoblotting and immunoprecipitation. Results showed that CP-101,606
      attenuated l-dopa-induced AIMs. In agreement with behavioral analysis, CP-101,606
      reduced the augmented pNR2B-Tyr1472 and its interactions with Fyn triggered
      during the l-dopa administration in the lesioned striatum of parkinsonian rats.
      Moreover, CP-101,606 also decreased the level of Ca(2+)/calmodulin-dependent
      protein kinase II at threonine-286 hyperphosphorylation (pCaMKII-Thr286), which
      was the downstream signaling amplification molecule of NMDAR overactivation and
      closely associated with LID. However, the protein level of NR2B and Fyn had no
      difference under the above conditions. These data indicate that the inhibition of
      the interactions of NR2B with Fyn and NR2B tyrosine phosphorylation may
      contribute to the CP-101,606-induced downregulation of NMDAR function and provide
      benefit for the therapy of LID. 

PMID- 25576966
TI  - The roles of liar intention, lie content, and theory of mind in children's
      evaluation of lies.
AB  - This study found that 7-, 9-, and 11-year-old children and young adults
      identified prosocial lies as lies less frequently and evaluated them less
      negatively than selfish lies (liar intention effect); lies about opinions were
      identified as lies less frequently and evaluated less negatively than those about
      reality (lie content effect). The lie content effect was more pronounced in the
      prosocial lies than in the selfish lies for both identification and evaluation.
      Overall, the older participants considered liar intention more than the younger
      participants in lie evaluation. For the child participants, second-order belief
      understanding correlated marginally with sensitivity to liar intention in the
      opinion lies, but not with content sensitivity. Finally, lie identification
      correlated with evaluation in the prosocial-opinion lies for all of the children.
      The independent effects of intention and content could potentially explain
      children's development in "white lie" understanding demonstrated in the
      literature. Although the content effect appears to stem from a more general
      concern for whether communication is about objective reality, the intention
      effect may involve theory of mind. 

PMID- 25576968
TI  - Reprogramming of somatic cells: possible methods to derive safe, clinical-grade
      human induced pluripotent stem cells.
AB  - Derivation of pluripotent stem cells from adult somatic tissues by reprogramming
      technology has opened new therapeutic possibilities. Current most efficient
      procedures for derivation of induced pluripotent stem (iPS) cells are based on
      the viral vectors, which represent the danger of insertional mutagenesis during
      incorporation of introduced genes into the host genome. To circumvent this
      problem, the new, safe, non-integrative and non-viral strategies of reprogramming
      have been developed. In this review we discuss novel DNA-free and viral-free
      methods of reprogramming to iPS cells including protein transduction, mRNA and
      microRNA delivery.

PMID- 25576967
TI  - Parenting predictors of cognitive skills and emotion knowledge in
      socioeconomically disadvantaged preschoolers.
AB  - This study examined the concurrent and longitudinal associations of parental
      responsiveness and inferential language input with cognitive skills and emotion
      knowledge among socioeconomically disadvantaged preschoolers. Parents and 2- to 4
      year-old children (mean age=3.21 years, N=284) participated in a parent-child
      free play session, and children completed cognitive (language, early literacy,
      early mathematics) and emotion knowledge assessments. Approximately 1 year later,
      children completed the same assessment battery. Parental responsiveness was coded
      from the videotaped parent-child free play sessions, and parental inferential
      language input was coded from transcripts of a subset of 127 of these sessions.
      All analyses controlled for child age, gender, and parental education, and
      longitudinal analyses controlled for initial skill level. Parental responsiveness
      significantly predicted all concurrent cognitive skills as well as literacy,
      math, and emotion knowledge 1 year later. Parental inferential language input was
      significantly positively associated with children's concurrent emotion knowledge.
      In longitudinal analyses, an interaction was found such that for children with
      stronger initial language skills, higher levels of parental inferential language
      input facilitated greater vocabulary development, whereas for children with
      weaker initial language skills, there was no association between parental
      inferential language input and change in children's vocabulary skills. These
      findings further our understanding of the roles of parental responsiveness and
      inferential language input in promoting children's school readiness skills.

PMID- 25576969
TI  - Neuroprotective effects of histone deacetylase inhibitors in brain ischemia.
AB  - Stroke resulting from cerebral ischemia or haemorrhage is a common cause of the
      death of neuronal cells and neurological dysfunction in humans. Finding
      therapeutics to improve outcome from brain ischemic injury has proved to be
      challenging. The efficacy of neuroprotective compounds identified in experimental
      brain ischemia models thus far have failed to successfully translate in clinical
      human trials. Recent experimental evidence indicates that inhibition of zinc
      dependent histone deacetylases can protect neuronal and oligodendroglial cells
      from the damaging effects of ischemic insult, which may contribute to improved
      functional outcome. In this review we briefly highlight the current data
      supporting a beneficial role of histone deacetylation in experimental brain
      ischemia. We also discuss the molecular mechanism of neuroprotection.

PMID- 25576970
TI  - NMDA receptor antagonists MK-801 and memantine induce tolerance to oxygen and
      glucose deprivation in primary cultures of rat cerebellar granule cells.
AB  - Preconditioning is an experimental strategy for reducing ischemic brain damage.
      There are reports that brief exposure of neurons to NMDA-receptor antagonists may
      be an adequate preconditioning stressor. We studied effects of preconditioning of
      the cerebellar granule cells (CGC) in primary culture by 30-minute exposure to
      NMDA receptor antagonists 0.5 MUM MK-801 or 5 MUM memantine. CGC were challenged
      with oxygen and glucose deprivation (OGD) or excitotoxic glutamate and cell
      viability was tested 24 h later using calcein/ethidium homodimer-1 staining. We
      studied glutamate-induced increases in 45Ca uptake and in the intracellular Ca2+
      level assessed with the fluorescent probe fluo-3. The number of living cells in
      OGD-treated cultures decreased by 42%. Preconditioning with MK-801 or memantine
      24 h earlier reduced cell death to 8% and 30% and 48 h earlier to 27% and 33%,
      respectively. Pretreatment with MK-801 followed by the standard MK-801 wash out
      was slightly cytoprotective in a glutamate excitotoxicity test performed
      immediately; the protection increased significantly 24 h after preconditioning.
      In both cases the extensive wash out of MK-801 after preconditioning resulted in
      loss of cytoprotection. The increase in the intracellular Ca2+ level evoked by
      glutamate was decreased 24 h after preconditioning and even halved in the
      neuronal cultures 48 h after preconditioning with MK-801 and memantine. Glutamate
      induced 45Ca uptake in these cells was decreased by 18%, irrespective of the time
      laps after preconditioning. These results demonstrate that preconditioning of CGC
      with NMDA receptor antagonists induces prolonged tolerance to OGD, which is
      accompanied by the reduction of glutamate-evoked calcium fluxes. The causal
      relationship between these effects may be suggested.

PMID- 25576971
TI  - The role of the GABA-A receptor of the adjacent intact dorsal root ganglion
      neurons in rats with neuropathic pain.
AB  - We aim to investigate the changes of The gamma-aminobutyric acid (GABA) signals
      in the adjacent intact dorsal root ganglion (DRG) and the contribution of these
      changes to the development and maintenance of neuropathic pain (NPP). After
      establishment of neuropathic pain model with the lumbar 5 spinal nerve ligation
      (L5 SNL), the GABA-evoked currents were recorded in the acutely dissociated L4
      DRG neurons using whole-cell patch clamp. Moreover, Muscimol or Bicuculline were
      respectively topically injected to the L4 DRG at the time of nerve injury and
      post-operative 5 days (POD5). The pain thresholds of hind paw were recorded. We
      found that the incidence and amplitude of GABA currents significantly decreased
      in the large and medium L4 DRG neurons after SNL (P<0.05). Furthermore, in the L5
      SNL rats, 20 MUg Muscimol injected immediately after injury caused a long-lasting
      attenuation of mechanical allodynia (P<0.05), whereas the thermal hyperalgesia
      was not alleviated (P>0.05). 0.15 MUg Bicuculline further decreased the pain
      thresholds (P<0.05) and reversed the pain-alleviating effects of Muscimol.
      However, at POD5, 20 MUg Muscimol only exhibited transient alleviating effects
      (P<0.05). In conclusion, the decrease of inhibition signal mediated by GABA-A
      receptor in the adjacent intact DRG neurons may be crucial in the development of
      hyperalgesia in NPP.

PMID- 25576972
TI  - Single course of antenatal betamethasone produces delayed changes in morphology
      and calbindin-D28k expression in a rat's cerebellar Purkinje cells.
AB  - In the current study, we analyzed the impact of antenatal betamethasone on
      macroscopic cerebellar development, Purkinje cell morphology and the expression
      of the neuroprotective protein calbindin-D28k. Pregnant rats (Sprague-Dawley)
      were randomly divided into two experimental groups: control (CONT) and
      betamethasone-treated (BET). At gestational day 20 (G20), BET dams were
      subcutaneously injected with a solution of 0.17 mg kg-1 of betamethasone, while
      CONT animals received a similar volume of saline. At postnatal days 22 (P22) and
      P52, BET and CONT offspring were behaviorally evaluated, and the cerebella were
      histologically and immunohistochemically processed. Animals that were prenatally
      treated with a single course of betamethasone exhibited long-lasting behavioral
      changes consistent with anxiety-like behavior in the open-field test, together
      with (1) reduced cerebellar weight and volume, (2) Purkinje cell dendritic
      atrophy, and (3) an overexpression of calbindin-D28k. The current results
      indicate that an experimental single course of betamethasone in pregnant rats
      produces long-lasting anxiety-like behaviors, together with macroscopic and
      microscopic cerebellar alterations.

PMID- 25576973
TI  - Interleukin 6 deficiency affects spontaneous activity of mice in age- and sex
      dependent manner.
AB  - We analyzed the role of interleukin 6 (IL-6) in modulation of the pattern of mice
      spontaneous activity. Wild type (WT) and IL-6 deficient mice of both sexes, young
      and aging, were housed individually and various types of their activity were
      recorded and analyzed with the Phenorack system in their home cages during 72
      hours-long sessions. All investigated groups of mice were active mainly during
      the dark phase of the 24-hours cycle. Generally, the IL-6 deficient animals were
      more active than their WT controls and females of both genotypes more active than
      males. Aging mice were less active than the sex and genotype-matched young
      animals. The independent variables (age, sex and genotype) strongly interacted,
      which suggests that the modulatory influence of IL-6 on mice behavior may be
      different in males and females and that it changes during aging. We conclude that
      under normal physiological conditions signaling of IL-6 via its receptor
      participates in modulation of the basic pattern of activity. This modulation
      differs in males and females and changes with aging.

PMID- 25576974
TI  - Assessment of postural stability in young healthy subjects based on directional
      features of posturographic data: vision and gender effects.
AB  - Directional characteristics of postural sway and their impact on postural
      stability control (PSC) still need to be clarified. To assess the directional
      characteristics of PSC, center-of-pressure (COP) while standing quiet was
      recorded and analyzed in 46 young healthy subjects. The participants completed
      five 60-s trials with 'eyes open' and five with 'eyes closed'. The control
      asymmetry was characterized using three standardized COP measures: mean sway
      velocity (V), sway ratio (SR), and sway directional index (DI). The COP data were
      low-pass filtered at 10 Hz. In such conditions the V, SR and DI revealed
      consistent and unique differences in both the anteroposterior (AP) and the
      mediolateral (ML) controls. Each of the COP measures showed the involvement of
      different neuromuscular and biomechanical mechanisms in the stabilization of
      standing posture. The DI documented a very stable proportion between frontal and
      saggital controls, with roughly 60% of the swaying movements being performed in
      the AP direction. The AP DI was significantly higher in comparison with the ML
      value (0.71+/-0.04 vs. 0.55+/-0.06). This proportion remained at the same level
      in both experimental groups and it was only slightly affected by the visual
      conditions. Analysis of the SR confirmed that to maintain stable stance the
      neuromuscular system must allocate 50% more effort to control AP stability. The
      results also documented gender-related differences in postural stability.
      Generally the female subjects appeared to have lower postural stability as
      evidenced by higher COM and COP velocities. Consequently the higher SR values
      observed in the female group indicate a need for higher neuromuscular efforts to
      maintain stable posture. The introduced here set of COP measures proved to be a
      valuable standard for static posturography, creating the opportunity for improved
      and reliable assessment of postural stability.

PMID- 25576975
TI  - Temporal dynamics of the Oppel-Kundt Illusion compared to the Muller-Lyer
      Illusion.
AB  - In psychophysical experiments, subjects reported whether the filled part of the
      Oppel-Kundt stimulus was longer than the empty one at different durations of the
      stimuli presentations. The experimental data yielded a smooth function indicating
      a gradual augmentation of the illusion strength within a relatively wide 100-1000
      ms interval of the exposure durations. On the contrary, the experiments with the
      Muller-Lyer stimuli showed a gradual decrease of the illusion magnitude within
      the same interval of expositions. In the supplementary experiments, the stimuli
      with uniformly filled or outlined rectangles of fixed duration were used; various
      combinations of the rectangles with the regular sequences of filling stripes were
      also taken. It was demonstrated that the superposition of the stimuli did not
      change the illusion strength noticeably. The results obtained in the study
      support the suggestion that the filled interval overestimation in the Oppel-Kundt
      stimulus may be related to spatiotemporal integration along a continuous path of
      neural excitation evoked by the real and illusory contours of the filling.

PMID- 25576976
TI  - Anxiolytic and antidepressive effects of electric stimulation of the
      paleocerebellar cortex in pentylenetetrazol kindled rats.
AB  - Anxiety and depression are component of interictal behavioral deteriorations that
      occur as a consequence of kindling, a procedure to induce chronic epilepsy. The
      aim of this study was to evaluate the possible effects of electrical stimulation
      (ES) of paleocerebellar cortex on anxiety and depressive-like behavior in a PTZ
      kindled epilepsy model. Kindling was induced via pentylenetetrazol (PTZ) (25.0
      mg/kg IP daily) during three weeks. Locomotion in open field, elevated plus-maze
      (EPM) and Porsolt forced swimming test have been used for the assessment of
      anxiety and depression-like behavior. ES (100 Hz) has been delivered to V-VII
      lobules of vermal cortex of kindled rats. ES of paleocerebellum reversed kindling
      induced reduction of crossings of central squares, increased rearings, and
      decreased the number of defecations in open field. The duration that kindled
      animals spent in the open arms of the EPM increased in post- ES period, and the
      number of enterings into the closed arms of the EPM decreased. The duration of
      the immobility response in the swimming test in kindled rats was reduced after
      ESs of paleocerebellum. In all: ES of paleocerebellar structures suppressed
      anxious and depressive-like behavior in PTZ-kindled rats.

PMID- 25576977
TI  - The neural correlates of specific executive dysfunctions in Parkinson's disease.
AB  - Several functional neuroimaging studies in patients with Parkinson's disease (PD)
      have suggested that changes in the fronto-parietal-striatal networks are
      associated with deficits in executive functioning. However, executive functions
      (EF) are multifaceted and include three dissociable components: working memory,
      response inhibition, and task-switching. This study investigated which component
      of executive functioning is most strongly associated with fronto-parietal
      striatal efficiency in PD. PD patients (with and without executive dysfunction),
      and age-matched healthy subjects, completed a battery of cognitive tests
      previously shown to discriminate among the three EF components. Principal
      component analysis conducted on the selected cognitive test variables yielded
      three expected EF components. The component scores were used in regression
      analysis to assess the relationship between the EF efficiency and blood
      oxygenation level-dependent (BOLD) signal related to performing the n-back, an
      experimental task that draws upon multiple components of executive functioning:
      working memory, response inhibition, and task-switching. We found distinct neural
      correlates of specific executive dysfunctions in patients with PD. However, all
      of them seem to be associated with fronto-parietal-striatal efficiency.

PMID- 25576978
TI  - Transplantation of human bone marrow stromal cell-derived neuroregenrative cells
      promotes functional recovery after spinal cord injury in mice.
AB  - Transplantation of bone marrow stromal cells (BMSCs) for spinal cord injury (SCI)
      has been shown to improve functional outcome. BMSCs can be easily obtained from
      bone marrow aspirate and have fewer problems in the clinical application for
      human SCI from the ethical and legal points of view. Recently, we produced cells
      with neural stem and/or progenitor cell property and neural regeneration
      supporting capacity from human bone marrow stromal cells (human bone marrow
      stromal cell-derived neuroregenerative cells: hBMSC-NRs). The aim of the present
      study was to clarify the effectiveness of transplantation of hBMSC-NRs to injured
      spinal cord of severe combined immunodeficiency (NOD/SCID) mice. Neurite
      outgrowth assay of PC-12 cells was performed. One week after a T9-level contusion
      SCI, hBMSCs or hBMSC-NRs were transplanted into the spinal cord. After the
      transplantation, functional and histological examinations were performed.
      Conditioned media of hBMSC-NRs significantly promoted the neurite outgrowth of PC
      12 cells in vitro. Transplanted hBMSC-NRs survived in the injured spinal cord 8
      weeks after SCI. Immunohistochemistry revealed that the density of serotonin
      positive fibers of the transplanted group was significantly higher than that of
      the control group at the epicenter and caudal segment to the injured site. The
      recovery of hind limb function of the hBMSC-NRs group was significantly better
      than that of the control group. In conclusion, hBMSC-NRs can be one of the
      realistic candidates for cell transplantation therapy for human SCI.

PMID- 25576979
TI  - Efficacy of GM6001 as an adjuvant to ceftriaxone in a neonatal rat model of
      Streptococcus pneumoniae meningitis.
AB  - Evidence has demonstrated that matrix metalloproteinases (MMPs) contribute to the
      pathophysiology of bacterial meningitis; therefore, MMP inhibitors may be a
      neuroprotective treatment for brain injury caused by meningitis because of their
      antiinflammatory effects. The objective of this study was to evaluate the effect
      of the MMP inhibitor GM6001 in a rat model of S. pneumoniae meningitis. For these
      experiments, 7-day-old Sprague-Dawley rats were randomly divided into an
      uninfected group, meningitis group, antibiotic group and GM6001+antibiotic group.
      Uninfected animals were sham infected with sterile saline. Rats in the other
      three groups were inoculated with S. pneumoniae and left untreated, treated with
      ceftriaxone, or treated with ceftriaxone combined with GM6001. Rats in the
      meningitis group were severely ill, and MMP-9 was significantly up-regulated. The
      change in brain water content was consistent with the MMP-9 level. A significant
      loss of neurons and impaired learning function were observed in the meningitis
      group. Treatment with the antibiotic and GM6001 significantly down-regulated the
      level of MMP-9, decreased the brain water content, attenuated neuronal injury and
      improved learning. Conclusions: GM6001 protected the brain from damage caused by
      S. pneumoniae, and this effect may occur via downregulating MMP-9 and decreasing
      brain water content.

PMID- 25576980
TI  - The value of susceptibility-weighted imaging (SWI) in patients with non-neonatal
      hypoxic-ischemic encephalopathy.
AB  - OBJECTIVE: In susceptibility-weighted imaging (SWI) in the normal brain, cortical
      veins appear hypointense due to paramagnetic properties of deoxy-hemoglobin.
      Global cerebral anoxia decreases cerebral oxygen metabolism, thereby increasing
      oxy-hemoglobin levels in cerebral veins. We hypothesized that a lower cerebral
      oxygen extraction fraction in comatose patients with non-neonatal hypoxic
      ischemic encephalopathy (IHE) produces a pattern of global rarefied or pseudo
      diminished cortical veins due to higher oxy-hemoglobin. PURPOSE: (1) To
      investigate the topographic relationship between susceptibility effects in
      cortical veins and related diffusion restrictions on diffusion-weighted imaging
      (DWI) in patients with IHE. (2) To relate imaging findings to patterns of altered
      resting activity on surface EEG. METHODS: Twenty-three IHE patients underwent
      MRI. EEG patterns were used to classify the depth of coma. Regional vs. global
      susceptibility changes on SWI and patterns of DWI restrictions were compared with
      the depth of coma. RESULTS: All patients exhibited areas of restricted cortical
      diffusion and SWI abnormalities. The dominant DWI restrictions encompassed
      widespread areas along the precuneus, frontal and parietal association cortices
      and basal ganglia. For SWI, nineteen patients had generalized bi-hemispherical
      patterns, the EEG patterns correlated with coma grades III-V. Four patients had
      focal decreases of deoxy-hemoglobin following DWI restrictions; associated with
      normal EEGs. CONCLUSION: Focal patterns of diamagnetic effects on SWI according
      to relative decreases in deoxy-hemoglobin due to reduced metabolic demand are
      associated with normal EEG in IHE patients. Global patterns indicated increased
      depth of coma and widespread cortical damage. CLINICAL RELEVANCE: The results
      indicate a potential diagnostic value of SWI in patients with IHE.

PMID- 25576981
TI  - Asphyxial cardiac arrest from drowning: giving E-CPR the cold shoulder.

PMID- 25576982
TI  - Computed tomography findings of complications resulting from cardiopulmonary
      resuscitation.
AB  - INTRODUCTION: This retrospective study was conducted to evaluate injuries related
      to cardiopulmonary resuscitation (CPR) and their associated factors using
      postmortem computed tomography (PMCT) and whole body CT after successful
      resuscitation. METHODS: The inclusion criteria were adult, non-traumatic, out-of
      hospital cardiac arrest patients who were transported to our emergency room
      between April 1, 2008 and March 31, 2013. Following CPR, PMCT was performed in
      patients who died without return of spontaneous circulation (ROSC). Similarly, CT
      scans were performed in patients who were successfully resuscitated within 72h
      after ROSC. The injuries associated with CPR were analysed retrospectively on CT
      images. RESULTS: During the study period, 309 patients who suffered out-of
      hospital cardiac arrest were transported to our emergency room and received CPR;
      223 were enrolled in the study. The CT images showed that 156 patients (70.0%)
      had rib fractures, and 18 patients (8.1%) had sternal fractures. Rib fractures
      were associated with older age (78.0 years vs. 66.0 years, p<0.01), longer
      duration of CPR (41min vs. 33min, p<0.01), and lower rate of ROSC (26.3% vs.
      55.3%, p<0.01). All sternal fractures occurred with rib fractures and were
      associated with a greater number of rib fractures, higher age, and a lower rate
      of ROSC than rib fractures only cases. Bilateral pneumothorax was observed in two
      patients with rib fractures. CONCLUSIONS: PMCT is useful for evaluating
      complications related to chest compression. Further investigations with PMCT are
      needed to reduce complications and improve the quality of CPR.

PMID- 25576983
TI  - Fulfilling caloric demands according to indirect calorimetry may be beneficial
      for post cardiac arrest patients under therapeutic hypothermia.
AB  - INTRODUCTION: We sought to investigate the energy requirements for patients under
      therapeutic hypothermia, and the relationship of energy fulfillment to patient
      outcome. PATIENTS AND METHODS: Adult patients admitted to our ICU after
      successful resuscitation from cardiac arrest for post resuscitation therapeutic
      hypothermia from April, 2012 to March, 2014 were enrolled. Body temperature was
      managed using the surface cooling device (Arctic Sun((r)), IMI). Calorimeter
      module on the ventilator (Engstrom carestation((r)), GE) was used for indirect
      calorimetry. Energy expenditure (EE) and respiratory quotient (RQ) were recorded
      continuously, as the average of the recent 2h. Measurements were started at the
      hypothermic phase and continued until the rewarming was completed. Cumulative
      energy deficit was calculated as the sum of difference between EE and daily
      energy provision for the 4 days during hypothermia therapy. RESULTS: Seven
      patients were eligible for analysis. Median EE for the hypothermic phase (day 1)
      was 1557.0kcald(-1). EE was elevated according with the rise in body temperature,
      reaching 2375kcald(-1) at normothermic phase. There was significant association
      between cumulative energy deficit and the length of ICU stay, among patients with
      good neurologic recovery (cerebral performance category (CPC): 1-3). CONCLUSION:
      The EE for patients under therapeutic hypothermia was higher than expected.
      Meeting the energy demand may improve patient outcome, as observed in the length
      of ICU stay for the present study. A larger, prospective study is awaited to
      validate the results of our study.

PMID- 25576984
TI  - Evolution of plant virus movement proteins from the 30K superfamily and of their
      homologs integrated in plant genomes.
AB  - Homologs of Tobacco mosaic virus 30K cell-to-cell movement protein are encoded by
      diverse plant viruses. Mechanisms of action and evolutionary origins of these
      proteins remain obscure. We expand the picture of conservation and evolution of
      the 30K proteins, producing sequence alignment of the 30K superfamily with the
      broadest phylogenetic coverage thus far and illuminating structural features of
      the core all-beta fold of these proteins. Integrated copies of pararetrovirus 30K
      movement genes are prevalent in euphyllophytes, with at least one copy intact in
      nearly every examined species, and mRNAs detected for most of them. Sequence
      analysis suggests repeated integrations, pseudogenizations, and positive
      selection in those provirus genes. An unannotated 30K-superfamily gene in
      Arabidopsis thaliana genome is likely expressed as a fusion with the At1g37113
      transcript. This molecular background of endopararetrovirus gene products in
      plants may change our view of virus infection and pathogenesis, and perhaps of
      cellular homeostasis in the hosts. 

PMID- 25576985
TI  - Detection of blaCTX-M-type genes in complex class 1 integrons carried by
      Enterobacteriaceae isolated from retail chicken meat in Brazil.
AB  - CTX-M-type extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae
      have been increasingly identified in humans and animals, and their potential
      transmission by contaminated food has been highlighted. In this study, we report
      for the first time the isolation of multidrug-resistant (MDR) Escherichia coli,
      Klebsiella pneumoniae and Proteus mirabilis strains harboring blaCTXM-2 or
      blaCTXM-8 gene variants in chicken meat sold in markets in southeast Brazil. In
      this regard, the genetic environment of the blaCTX-M-2 gene is composed of a
      complex class 1 integron and an ISCR1-associated sequence with dfr and/or aadA
      gene cassettes located within the variable region. In summary, chicken meat may
      be a reservoir of MDR Enterobacteriaceae harboring blaCTX-M-type genes, which is
      a public health concern. 

PMID- 25576986
TI  - The effect of surface properties of polycrystalline, single phase metal coatings
      on bacterial retention.
AB  - In the food industry microbial contamination of surfaces can result in product
      spoilage which may lead to potential health problems of the consumer. Surface
      properties can have a substantial effect on microbial retention. The surface
      characteristics of chemically different coatings (Cu, Ti, Mo, Ag, Fe) were
      defined using white light profilometry (micro-topography and surface features),
      atomic force microscopy (nano-topography) and physicochemical measurements. The
      Ag coating had the greatest topography measurements and Fe and Mo the least. Mo
      was the most hydrophobic coating (lowest gammaAB,gamma(+), gamma(-)) whilst Ag
      was the most hydrophilic (greatest gammaAB,gamma(+), gamma(-)). The
      physicochemical results for the Fe, Ti and Cu coatings were found to lie between
      those of the Ag and Mo coatings. Microbiological retention assays were carried
      out using Listeria monocytogenes, Escherichia coli and Staphylococcus aureus in
      order to determine how surface properties influenced microbial retention. It was
      found that surface chemistry had an effect on microbial retention, whereas the
      shape of the surface features and nano-topography did not. L. monocytogenes and
      S. aureus retention to the surfaces were mostly affected by surface micro
      topography, whereas retention of E. coli to the coatings was mostly affected by
      the coating physicochemistry. There was no trend observed between the bacterial
      cell surface physicochemistry and the coating physicochemistry. This work
      highlights that different surface properties may be linked to factors affecting
      microbial retention hence, the use of surface chemistry, topography or
      physicochemical factors alone to describe microbial retention to a surface is no
      longer adequate. Moreover, the effects of surface parameters on microbial
      retention should be considered individually for each bacterial genus. 

PMID- 25576987
TI  - Selective catalytic conversion of bio-oil over high-silica zeolites.
AB  - Four high silica zeolites, i.e., HSZ-385, 890, 960, and 990 were utilized for the
      selective catalytic conversion of bio-oil from Fallopia japonica to certain
      chemicals in a fixed-bed reactor. The Beta-type HSZ-960 zeolite showed the
      highest selectivity to hydrocarbons, especially to aromatics as well as PAH
      compounds with the lowest unwanted chemicals while HSZ-890 showed high
      selectivity to aromatics. NH3-Temperature Programmed Desorption (TPD) analysis
      indicated that different amounts of acid sites in different zeolites determined
      the catalytic activity for the oxygen removal from bio-oil, in which the acid
      sites at low temperature (LT) region gave more contribution within the utilized
      temperature region. The reusability test of HSZ-960 showed the stability of
      hydrocarbons yield at higher temperature due to the significant contribution of
      coke gasification which assisted further deoxygenation of bio-oil. These results
      provide a guidance to select suitable zeolite catalysts for the upgrading of bio
      oil in a practical process. 

PMID- 25576988
TI  - Multi-gene genetic programming based predictive models for municipal solid waste
      gasification in a fluidized bed gasifier.
AB  - A multi-gene genetic programming technique is proposed as a new method to predict
      syngas yield production and the lower heating value for municipal solid waste
      gasification in a fluidized bed gasifier. The study shows that the predicted
      outputs of the municipal solid waste gasification process are in good agreement
      with the experimental dataset and also generalise well to validation (untrained)
      data. Published experimental datasets are used for model training and validation
      purposes. The results show the effectiveness of the genetic programming technique
      for solving complex nonlinear regression problems. The multi-gene genetic
      programming are also compared with a single-gene genetic programming model to
      show the relative merits and demerits of the technique. This study demonstrates
      that the genetic programming based data-driven modelling strategy can be a good
      candidate for developing models for other types of fuels as well. 

PMID- 25576989
TI  - Study on loading coefficient in steam explosion process of corn stalk.
AB  - The object of this work was to evaluate the effect of loading coefficient on
      steam explosion process and efficacy of corn stalk. Loading coefficient's
      relation with loading pattern and material property was first revealed, then its
      effect on transfer process and pretreatment efficacy of steam explosion was
      assessed by established models and enzymatic hydrolysis tests, respectively, in
      order to propose its optimization strategy for improving the process economy.
      Results showed that loading coefficient was mainly determined by loading pattern,
      moisture content and chip size. Both compact loading pattern and low moisture
      content improved the energy efficiency of steam explosion pretreatment and
      overall sugar yield of pretreated materials, indicating that they are desirable
      to improve the process economy. Pretreatment of small chip size showed opposite
      effects in pretreatment energy efficiency and enzymatic hydrolysis performance,
      thus its optimization should be balanced in investigated aspects according to
      further techno-economical evaluation. 

PMID- 25576990
TI  - Performance of nitrate-dependent anaerobic ferrous oxidizing (NAFO) process: a
      novel prospective technology for autotrophic denitrification.
AB  - Nitrate-dependent anaerobic ferrous oxidizing (NAFO) is a valuable biological
      process, which utilizes ferrous iron to convert nitrate into nitrogen gas,
      removing nitrogen from wastewater. In this work, the performance of NAFO process
      was investigated as a nitrate removal technology. The results showed that NAFO
      system was feasible for autotrophic denitrification. The volumetric loading rate
      (VLR) and volumetric removal rate (VRR) under steady state were 0.159+/-0.01 kg
      N/(m(3) d) and 0.073+/-0.01 kg-N/(m(3) d), respectively. In NAFO system, the
      effluent pH was suggested as an indicator which demonstrated a good correlation
      with nitrogen removal. The nitrate concentration was preferred to be less than
      130 mg-N/L. Organic matters had little influence on NAFO performance. Abundant
      iron compounds were revealed to accumulate in NAFO sludge with peak value of
      51.73% (wt), and they could be recycled for phosphorus removal, with capacity of
      16.57 mg-P/g VS and removal rate of 94.77+/-2.97%, respectively.

PMID- 25576991
TI  - The contrasting responses of soil microorganisms in two rice cultivars to
      elevated ground-level ozone.
AB  - Although elevated ground-level O3 has a species-specific impact on plant growth,
      the differences in soil biota responses to O3 pollution among rice cultivars are
      rarely reported. Using O3 Free-Air Concentration Enrichment, the responses of the
      rhizospheric bacterial communities in the O3-tolerant (YD6) and the O3-sensitive
      (IIY084) rice cultivars to O3 pollution and their differences were assessed by
      pyrosequencing at rice tillering and anthesis stages. Elevated ground-level O3
      negatively influenced the bacterial community in cultivar YD6 at both rice growth
      stages by decreasing the bacterial phylogenetic diversities and response ratios.
      In contrast, in cultivar IIY084, the bacterial community responded positively at
      the rice tillering stage under O3 pollution. However, several keystone bacterial
      guilds were consistently negatively affected by O3 pollution in two rice
      cultivars. These findings indicate that continuously O3 pollution would
      negatively influence rice agroecosystem and the crop cultivar is important in
      determining the soil biota responses to elevated O3.

PMID- 25576992
TI  - Rubella.
AB  - Rubella remains an important pathogen worldwide, with roughly 100,000 cases of
      congenital rubella syndrome estimated to occur every year. Rubella-containing
      vaccine is highly effective and safe and, as a result, endemic rubella
      transmission has been interrupted in the Americas since 2009. Incomplete rubella
      vaccination programmes result in continued disease transmission, as evidenced by
      recent large outbreaks in Japan and elsewhere. In this Seminar, we provide
      present results regarding rubella control, elimination, and eradication policies,
      and a brief review of new laboratory diagnostics. Additionally, we provide novel
      information about rubella-containing vaccine immunogenetics and review the
      emerging evidence of interindividual variability in humoral and cell-mediated
      innate and adaptive immune responses to rubella-containing vaccine and their
      association with haplotypes and single-nucleotide polymorphisms across the human
      genome.

PMID- 25576993
TI  - The primary open-angle african american glaucoma genetics study: baseline
      demographics.
AB  - PURPOSE: To describe the baseline characteristics of the Primary Open-Angle
      African American Glaucoma Genetics (POAAGG) study cohort, the largest African
      American population with primary open-angle glaucoma (POAG) recruited at a single
      institution (University of Pennsylvania [UPenn], Department of Ophthalmology,
      Scheie Eye Institute) to date. DESIGN: Population-based, cross-sectional, case
      control study. PARTICIPANTS: A total of 2520 African American subjects aged 35
      years or more who were recruited from the greater Philadelphia, Pennsylvania
      area. METHODS: Each subject underwent a detailed interview and eye examination.
      The interview assessed demographic, behavioral, medical, and ocular risk factors.
      Current ZIP codes surrounding UPenn were recorded and US census data were queried
      to infer socioeconomic status. The eye examination included measurement of visual
      acuity (VA) and intraocular pressure, and a detailed anterior and posterior
      segment examination, including gonioscopy, dilated fundus and optic disc
      examination, visual fields, stereo disc photography, optical coherence
      tomography, and measurement of central corneal thickness. MAIN OUTCOME MEASURES:
      The baseline characteristics of gender, age, and glaucoma diagnosis were
      collected. Body mass index (BMI), hypertension, diabetes, alcohol and tobacco
      use, ocular conditions (including blindness, cataract, nonproliferative diabetic
      retinopathy, and age-related macular degeneration), and use of ocular medication
      and surgery were examined. Median population density, income, education level,
      and other socioeconomic measures were determined for the study cohort. RESULTS:
      Of the 2520 African Americans recruited to the POAAGG study to date, 2067
      (82.0%), including 807 controls and 1260 POAG cases, met all inclusion criteria
      and completed the detailed clinical ocular examination. Cases were more likely to
      have a lower BMI (P < 0.01) and report a history of blindness (VA of <=20/200; P
      < 0.001), whereas controls were more likely to have diabetes (P < 0.001), have
      nonproliferative diabetic retinopathy (P = 0.02), and be female (P < 0.001).
      Study participants were drawn largely from predominantly African American
      neighborhoods of low income, high unemployment, and lower education surrounding
      UPenn. CONCLUSIONS: The POAAGG study has currently recruited more than 2000
      African Americans eligible for a POAG genetics study. Blindness and low BMI were
      significantly associated with POAG. This population was predominantly recruited
      from neighborhoods whose population income exists at or near the federal poverty
      level.

PMID- 25576994
TI  - Therapies for macular edema associated with central retinal vein occlusion: a
      report by the American Academy of Ophthalmology.
AB  - PURPOSE: To review the available evidence regarding the safety and efficacy of
      therapies for the treatment of macular edema (ME) associated with central retinal
      vein occlusion (CRVO). METHODS: A literature search of the PubMed database was
      last conducted in March 2014 with no date restrictions but limited to articles
      published in English. A literature search of the Cochrane Library was also
      conducted in March 2014 with no date restrictions and without a language
      limitation. The combined searches yielded 108 citations, of which 20 were deemed
      clinically relevant for the Ophthalmic Technology Assessment Committee
      Retina/Vitreous panel to review in full text. Three additional studies were also
      identified for panel review. The level of evidence of these selected studies was
      reviewed by the panel methodologist. RESULTS: There were 7 citations representing
      4 clinical trials that provided level I evidence supporting the use of anti
      vascular endothelial growth factor (VEGF) pharmacotherapies for ME associated
      with CRVO, including intravitreal ranibizumab (2), aflibercept (3), and
      bevacizumab (2). There were 3 citations representing 2 studies with level I
      evidence for intravitreal corticosteroid injection with dexamethasone
      intravitreal implant (2 citations) or triamcinolone (1 citation), although
      cataract and glaucoma were observed in these studies. Level I evidence is
      available on the limited benefit of macular grid-pattern laser photocoagulation
      (1 citation). Eight other citations reviewed were rated as level II, and 4
      citations were rated as level III. Long-term efficacy results (>=2 years of
      follow-up) are limited to intravitreal ranibizumab at this time, and few studies
      have evaluated combination therapy with anti-VEGF and corticosteroid versus
      monotherapy of either class of drug. CONCLUSIONS: Level I evidence indicates that
      intravitreal anti-VEGF pharmacotherapy is safe and effective over 2 years for ME
      associated with CRVO and that delay in treatment is associated with worse visual
      outcomes. In addition, level I evidence demonstrates short-term efficacy of
      intravitreal corticosteroid but also an association with a higher frequency of
      adverse events.

PMID- 25576995
TI  - Assessment of accuracy and precision of quantification of ultra-widefield images.

PMID- 25576996
TI  - Why is it hard to make progress in assessing children's decision-making
      competence?
AB  - BACKGROUND: For decades, the discussion on children's competence to consent to
      medical issues has concentrated around normative concerns, with little progress
      in clinical practices. Decision-making competence is an important condition in
      the informed consent model. In pediatrics, clinicians need to strike a proper
      balance in order to both protect children's interests when they are not fully
      able to do so themselves and to respect their autonomy when they are. Children's
      competence to consent, however, is currently not assessed in a standardized way.
      Moreover, the correlation between competence to give informed consent and age in
      children has never been systematically investigated, nor do we know which factors
      exactly contribute to children's competence.This article aims at identifying
      these gaps in knowledge and suggests options for dealing with the obstacles in
      empirical research in order to advance policies and practices regarding
      children's medical decision-making competence. DISCUSSION: Understanding
      children's competency is hampered by the law. Legislative regulations concerning
      competency are established on a strong presumption that persons older than a
      certain age are competent, whereas younger persons are not. Furthermore, a number
      of contextual factors are believed to be of influence on a child's decision
      making competence: the developmental stage of children, the influence of parents
      and peers, the quality of information provision, life experience, the type of
      medical decision, and so on. Ostensibly, these diverse and extensive barriers
      hinder any form of advancement in this conflicted area. Addressing these
      obstacles encourages the discussion on children's competency, in which the most
      prominent question concerns the lack of a clear operationalization of children's
      competence to consent. Empirical data are needed to substantiate the discussion.
      SUMMARY: The empirical approach offers an opportunity to give direction to the
      debate. Recommendations for future research include: studying a standardized
      assessment instrument covering all four relevant dimensions of competence
      (understanding, reasoning, appreciation, expressing a choice), including a study
      population of children covering the full age range of 7 to 18 years, improving
      information provision, and assessing relevant contextual data.

PMID- 25576997
TI  - Structural adjustment and public spending on health: evidence from IMF programs
      in low-income countries.
AB  - The relationship between health policy in low-income countries (LICs) and
      structural adjustment programs devised by the International Monetary Fund (IMF)
      has been the subject of intense controversy over past decades. While the
      influence of the IMF on health policy can operate through various pathways, one
      main link is via public spending on health. The IMF has claimed that its programs
      enhance government spending for health, and that a number of innovations have
      been introduced to enable borrowing countries to protect health spending from
      broader austerity measures. Critics have pointed to adverse effects of Fund
      programs on health spending or to systematic underfunding that does not allow
      LICs to address health needs. We examine the effects of Fund programs on
      government expenditures on health in low-income countries using data for the
      period 1985-2009. We find that Fund programs are associated with higher health
      expenditures only in Sub-Saharan African LICs, which historically spent less than
      any other region. This relationship turns negative in LICs in other regions. We
      outline the implications of these findings for health policy in a development
      context. 

PMID- 25576998
TI  - Extent of margin involvement, lymphovascular invasion, and extensive intraductal
      component predict for residual disease after wide local excision for breast
      cancer.
AB  - In the present study, we identified predictors of residual disease after an
      inadequate wide local excision. Residual tumor was more likely when tumor was
      present at the inked margin, when more than a single radial margin was affected,
      and in tumors associated with lymphovascular invasion and an extensive
      intraductal component. BACKGROUND: Positive margins after wide local excision
      (WLE) increase the probability of residual disease, and additional surgery is
      often recommended. However, residual tumor will be found in only two thirds of
      cases, suggesting that additional surgery can be avoided in many instances. In
      the present study, we sought to establish the frequency of residual tumor when
      the surgical margins are inadequate and to identify factors that predict for
      residual tumor. MATERIALS AND METHODS: A retrospective review was performed of
      720 consecutive patients who had undergone WLE for ductal carcinoma in situ and
      nonmetastatic breast cancer at a single unit from January 1, 2004 to December 31,
      2010. RESULTS: At least a single radial margin was affected (either involved or
      close, defined as tumor < 1 mm from the margin) in 244 patients who had undergone
      WLE, and either the anterior or posterior margin was affected in another 103
      patients. Reoperation was performed in 215 patients with affected radial margins
      and 9 others with affected anterior or posterior margins. Residual disease was
      found in 98 of 224 patients (43.8%) and was more likely when tumor was present at
      the inked margin, when > 1 radial margin was affected, and when lymphovascular
      invasion (LVI) or an extensive intraductal component (EIC) was present. The
      association with tumor size was of borderline significance. No association was
      found with tumor histologic type or patient age. CONCLUSION: Additional
      evaluation is needed to determine whether additional surgery can be safely
      omitted in women with tumors without LVI or EIC when a single radial margin has
      been deemed to be close.

PMID- 25576999
TI  - Hungry today, unhappy tomorrow? Childhood hunger and subjective wellbeing later
      in life.
AB  - I use anchoring vignettes to show that, on data for eleven European countries,
      exposure to episodes of hunger in childhood leads people to adopt lower
      subjective standards to evaluate satisfaction with life in adulthood. I also show
      that, as a consequence, estimates of the association between childhood starvation
      and late-life wellbeing that do not allow for reporting heterogeneity are biased
      towards finding a positive correlation. These results highlight the need to
      consider rescaling when drawing inference on subjective outcomes. 

PMID- 25577001
TI  - A review of some recent studies on the stable isotope profiling of
      methylamphetamine: Is it a useful adjunct to conventional chemical profiling?
AB  - This paper reviews a body of work published by the authors over a number of years
      aimed at providing a complementary "signature" to conventional chemical profiling
      of methylamphetamine. The work, beginning in 2009, was undertaken because of the
      changing nature of clandestine methylamphetamine manufacture which has seen a
      dramatic rise in production and a major shift to a higher quality product. As
      manufacturing methods changed and methylamphetamine purity increased some
      conventional drug profiling techniques became less useful as an intelligence
      tool. For instance, the value of the organic impurity profile, a mainstay of
      conventional profiling, decreases as there are fewer impurities present in seized
      samples. However, whilst many seizures may contain less conventional chemical
      intelligence another property of the methylamphetamine molecule is always
      available, i.e. the light element stable isotope ratios. The stable isotope
      ratios of carbon, hydrogen and nitrogen are an integral part of the
      methylamphetamine molecule itself. This review describes previous work by the
      authors and by researchers in other national laboratories to investigate and
      implement the use of stable isotope ratios as an everyday methylamphetamine
      profiling tool. It also looks at how powerful this technique can be when used to
      compare samples from different seizures. 

PMID- 25577002
TI  - Provenancing of unidentified World War II casualties: Application of strontium
      and oxygen isotope analysis in tooth enamel.
AB  - In 2010 and 2012 two sets of unidentified human remains of two World War II
      soldiers were recovered in the area where the 1944-1945 Kapelsche Veer bridgehead
      battle took place in The Netherlands. Soldiers of four Allied nations: British
      Royal Marine Commandos, Free Norwegian Commandos, Free Poles and Canadians,
      fought against the German Army in this battle. The identification of these two
      casualties could not be achieved using dental record information of DNA analysis.
      The dental records of Missing in Action soldiers of the Allied nations did not
      match with the dental records of the two casualties. A DNA profile was determined
      for the casualty found in 2010, but no match was found. Due to the lack of
      information on the identification of the casualties provided by routine methods,
      an isotope study was conducted in teeth from the soldiers to constrain their
      provenance. The isotope study concluded that the tooth enamel isotope composition
      for both casualties matched with an origin from the United Kingdom. For one of
      the casualties a probable origin from the United Kingdom was confirmed, after the
      isotope study was conducted, by the recognition of a characteristic belt buckle
      derived from a Royal Marine money belt, only issued to British Royal Marines,
      found with the remains of the soldier. 

PMID- 25577003
TI  - A global survey of the stable isotope and chemical compositions of bottled and
      canned beers as a guide to authenticity.
AB  - This study presents a dataset, derived from the analysis of 162 bottled and
      canned beers from around the globe, which may be used for comparison with
      suspected counterfeit or substitute products. The data comprise delta2H and
      delta18O compositions of the whole beer and delta13C compositions of the dry
      residue (mostly sugar) together with the concentrations of five anions (F, Cl,
      NO3, SO4, PO4) and seven cations (Ca, K, Mg, SiO2, V, Mn, Sr). A strong
      correlation, consistent with natural waters but offset from the Global Meteoric
      Water Line, was observed between the delta2H/delta18O composition of the beers.
      The extent of the offset could be explained by the brewing process and the
      alcohol and sugars present in the beers. Correlations between inorganic analytes
      were consistent with the addition of salts in the brewing process. Beers were
      classified as follows: ale, lager, stout or wheat-beer and the chemical
      composition was found to be characteristic of the assigned type, with lagers
      being the most readily classified. A combination of chemical and isotopic data
      was found to be characteristic of the geographical origin (on a continental
      scale) and could most easily identify beers from Australasia or Europe. A global
      map of delta18O data revealed a geo-spatial distribution that mirrored existing
      maps of the isotopic composition of annual precipitation. This confirmed a
      commonsense view that local precipitation will be the primary source for the
      water used in brewing. Using this isoscape (or alcoscape) it may be possible to
      assess the geographical origins of samples for which genuine comparative samples
      cannot be obtained.

PMID- 25577004
TI  - The potential for application of ink stable isotope analysis in questioned
      document examination.
AB  - We investigated a novel application of stable isotope abundance analysis of
      nitrogen (15N), carbon (13C), hydrogen (2H), and oxygen (18O) to characterize pen
      ink. We focused on both ballpoint and gel pen inks. We found that the isotope
      ratios of ink from pens purchased together in a package were similar and within
      package stable isotope ratio variability was not significantly larger than the
      variability of isotope reference materials used during analysis. In contrast, the
      isotope ratios of ink from pens of the same brand purchased in three states of
      the continental USA were significantly different from each other and there was
      isotope ratio variation among pens of the same brand but different, unknown
      production periods. The stable isotope ratios of inked paper were statistically
      distinguishable using measured delta15N values. Paper inked with different gel
      pens was statistically distinguishable using measured delta2H values. The
      capacity of stable isotope ratios to differentiate among ballpoint inks as well
      as gel inks shows that stable isotope analysis may be a useful and quantifiable
      investigative technique for questioned document examination, although current
      sample size requirements limit its utility. Application of the technique in
      casework will require the development of micro-scale sampling and analysis
      methods.

PMID- 25577005
TI  - Identification of the geographical place of origin of an unidentified individual
      by multi-isotope analysis.
AB  - A multi-isotope investigation (Sr and Pb isotopes and delta18O, delta13C and
      delta15N) was applied to bone and teeth from an unidentified male found drowned
      in the"IJ" Ruyterkade in Amsterdam, The Netherlands in March of 1999. The
      individual remained unidentified until mid 2013, after the isotope study was
      completed. Coupled delta13C and delta15N values in bone collagen recovered from
      rib and femur are consistent with an omnivore living in a region where C3-type
      diet dominates (i.e. Europe). Integrated Sr and Pb isotopes and delta18O values
      in canine and third molar teeth and femur and rib bone data exclude extended
      residence in north-west Europe and particularly The Netherlands. Characteristic
      Pb isotope ratios coupled with inferred delta18O values of drinking water argue
      for a most probable place of origin for the unidentified individual in west and
      south Poland, south-east Slovakia and the region of Ukraine-Romania-Bulgaria,
      specifically the region associated with the Carpathian Mountains. Independent of
      the isotope study, the Cold Case Team made a positive identification with an
      individual from south-west Poland, validating the results of the multiple
      isotopic approach.

PMID- 25577006
TI  - Biometrics from the carbon isotope ratio analysis of amino acids in human hair.
AB  - This study compares and contrasts the ability to classify individuals into
      different grouping factors through either bulk isotope ratio analysis or amino
      acid-specific isotope ratio analysis of human hair. Using LC-IRMS, we measured
      the isotope ratios of 14 amino acids in hair proteins independently, and
      leucine/isoleucine as a co-eluting pair, to provide 15 variables for
      classification. Multivariate analysis confirmed that the essential amino acids
      and non-essential amino acids were mostly independent variables in the
      classification rules, thereby enabling the separation of dietary factors of
      isotope intake from intrinsic or phenotypic factors of isotope fractionation.
      Multivariate analysis revealed at least two potential sources of non-dietary
      factors influencing the carbon isotope ratio values of the amino acids in human
      hair: body mass index (BMI) and age. These results provide evidence that compound
      specific isotope ratio analysis has the potential to go beyond region-of-origin
      or geospatial movements of individuals-obtainable through bulk isotope
      measurements-to the provision of physical and characteristic traits about the
      individuals, such as age and BMI. Further development and refinement, for example
      to genetic, metabolic, disease and hormonal factors could ultimately be of great
      assistance in forensic and clinical casework. 

PMID- 25577007
TI  - Isotopic profiling of seized benzylpiperazine and trifluoromethylphenylpiperazine
      tablets using delta13C and delta15N stable isotopes.
AB  - This paper demonstrates the use of isotopic analysis of 23 benzylpiperazine (BZP)
      and trifluoromethylphenylpiperazine (TFMPP) containing tablets seized on two
      independent occasions by the Northern Territory (NT) Police, Australia. Isolation
      (High Performance Liquid Chromatography (HPLC)) of BZP and TFMPP followed by
      Isotope Ratio Mass Spectrometry (IRMS) (carbon and nitrogen stable isotopes)
      analysis was performed. Results are presented for delta13C and delta15N values of
      the respective piperazine analogues. The isotopic data and statistical analysis
      suggest a common source of manufacture for the BZP samples but suggest different
      sources for the TFMPP isolated from the corresponding BZP containing tablets
      investigated. The use of IRMS in this case study demonstrated the ability to
      obtain information regarding the BZP/TFMPP sources unattainable via conventional
      chemical analysis.

PMID- 25577008
TI  - Precursor discrimination of designer drug benzylpiperazine using delta13C and
      delta15N stable isotopes.
AB  - Advances in analytical technology and emerging techniques have resulted in the
      increased exploitation of chemical and isotopic profiling for source
      linkage/discrimination of illicit drugs for forensic purposes. Although not
      routinely used for illicit drug investigations, such information has been
      obtained and its application demonstrated through the use of isotope ratio mass
      spectrometry (IRMS). There is a solid platform of research available relating to
      the isotopic analysis of methylenedioxymethamphetamine (MDMA) and methamphetamine
      (MA), however with the recently flourishing designer drug market it was of
      interest to examine the isotopic profiles of the popular 'party drug'
      benzylpiperazine hydrochloride (BZP.HCl). A preliminary analysis of delta13C and
      delta15N isotopic ratios in BZP.HCl products and corresponding synthetic
      intermediates (piperazine.HCl) synthesized in-house from three different
      precursor suppliers was conducted using IRMS. Analysis of the delta13C and
      delta15N isotopic data indicated that discrimination and correct grouping of all
      the intermediates and some of the product samples examined in this study were
      achievable.

PMID- 25577009
TI  - Tracking mobility using human hair: What can we learn from lead and strontium
      isotopes?
AB  - The isotope ratios of strontium (Sr) and lead (Pb) in water derive from local
      geology and their isotopic signature can be linked to the age and type of
      underlying bedrocks and soils (if applicable), and are transferred up the food
      chain. Both elements are transferred to human blood through diet and water, and
      some of it will ultimately be incorporated into the hair structure, making Sr and
      Pb isotopes interesting tools for tracing human mobility. In this study, we
      analyzed both the elemental concentration and isotope ratios of Sr and Pb from
      four different women of different ages to monitor their permanent relocation from
      central France to Eastern Canada during the summer 2012. For comparison, we also
      characterized bulk hair samples of sedentary individuals and local tap waters
      from their regions of origin and of settlement. Our results indicate that the
      87Sr/86Sr and 206Pb/204Pb ratios are significantly modified by the change of
      environment, but also confirm that human hair compositions are impacted by other
      external factors (such as dust). Sr and Pb isotope systematics demonstrate their
      added value for detecting human mobility, but require further studies to better
      constrain the main sources and processes controlling their respective budgets in
      human hair for provenancing purposes.

PMID- 25577010
TI  - Provenancing of unidentified corpses by stable isotope techniques - presentation
      of case studies.
AB  - Stable isotope methods can be used to determine the provenance of unidentified
      corpses. Body tissue materials such as teeth, bone, hair and nail taken from
      mortal remains provide information of different time periods of an individuals'
      life from childhood to death. Tissues of newborns contain provenance information
      of different time periods during pregnancy of the child's mother. The results of
      stable isotope analyses of body residues of two adults and a newborn found in
      Germany between 2010 and 2012 are presented. To determine the geographic origin
      and movements of unknown individuals, stable isotopes of hydrogen, carbon,
      nitrogen and sulphur were analysed in hair and bone collagen samples. Amino acid
      composition and, as a consequence, delta2H, delta13C, delta15N, and delta34S
      values in human keratin and bone collagen are different. Consequently correction
      factors were determined to compare isotopic data of bone collagen with those of
      an extensive worldwide reference hair collection. The isotopic signatures in hair
      and in bone collagen samples were compared to geographical groups of reference
      hair samples by canonical discriminant analysis. The results served as the basis
      for providing provenance constraints for the unidentified persons as requested by
      the police and prosecution. Ultimately the individuals were identified; hence the
      isotopic provenance interpretations can be critically evaluated and are shown to
      be successful.

PMID- 25577011
TI  - [Nicolas Lemery, apothicary and chemist].

PMID- 25577012
TI  - In search of innovative therapeutics for neuropsychiatric disorders: the case of
      neurodegenerative diseases.
AB  - The recent medical literature highlights the lack of new drugs able to prevent or
      treat neurodegenerative diseases such as Alzheimer disease or Parkinson disease.
      Yet, the prevalence of these diseases is growing, related to increasing life
      expectancy, and is leading to a rise in their economic and social cost. At the
      same time, pharmaceutical companies are reducing or halting their investment in
      neuropharmacological research. Why have advances in basic neuroscience and our
      understanding of these diseases not allowed innovative discoveries in drug
      research? This review will try to explain this failure and suggest possible
      solutions: develop basic and clinical research but with the emphasis on
      translational and truly collaborative research; improve preclinical studies by
      developing more appropriate animal models, using new biomarkers and methodologies
      such as imaging suitable for clinical trials, providing worthwhile information on
      the ability of the drug to reach its intended target and induce significant
      pharmacological changes; build a new system of research management, based on
      stronger interdisciplinary relations between preclinical and clinical research
      and including the introduction of international precompetitive research between
      academic teams, start-up companies and pharmaceutical laboratories; hold early
      discussions with the regulatory authorities during preclinical studies and at the
      beginning of clinical trials in order to validate the methodological approaches;
      involve patients' associations in this new organization of research. These
      changes should help to ensure the discovery of effective treatments for these
      pathologies. 

PMID- 25577013
TI  - [Fecal microbiota transplantation: review].
AB  - Fecal microbiota transplantation (FMT) has gained an increasing medical interest,
      since the recognition of the role of disturbed microbiota in the development of
      various diseases. To date, FMT is an established treatment modality for multiple
      recurrent Clostridium difficile infection (RCDI), despite lack of standardization
      of the procedure. Persisting normalization of the disturbed colonic microbiota
      associated with RCDI seems to be responsible for the therapeutic effect of FMT.
      For other diseases, FMT should be considered strictly experimental, only offered
      to patients in an investigational clinical setting. Although the concept of FMT
      is appealing, current expectations should be damped until future evidence arises.

PMID- 25577014
TI  - Formulation and stability study of a pediatric 2% phenylephrine hydrochloride eye
      drop solution.
AB  - INTRODUCTION: We present formulation and stability evaluation of a 2% (w/v)
      phenylephrine hydrochloride biocompatible eye drop solution, routinely prepared
      in hospital pharmacy under aseptic conditions, for retinal examination of
      neonates and premature infants. MATERIALS AND METHODS: Eye drop solution was
      formulated by dissolution of phenylephrine hydrochloride and disodium hydrogen
      phosphate as buffering agent in sterile water for injection and sodium chloride
      for injection as isotonic agent. The previous solution was sterile filtered
      through under aseptic conditions, in an iso class 5 air quality clean room under
      horizontal laminar airflow hood. Physical stability (visual inspection,
      osmolality measurements), chemical stability (pH measurement, phenylephrine assay
      by liquid chromatography coupled with an ultra-high resolution and accurate mass)
      and sterility evaluation of phenylephrine eye drop solution stored at ambient
      temperature were studied during 60 days. RESULTS AND DISCUSSION: The formulated
      eye drop solution had a pH of 6.90+/-0.05 and an osmolality of 285+/-2 mOsm/kg.
      Throughout the 60 days study the solutions remained clear without any
      precipitation or color modification, sterility was maintained, pH and osmolality
      were not significantly modified and no significant loss of product was detected
      using liquid chromatography coupled with an ultra-high resolution and accurate
      mass instrument suggesting the lack of degradation. CONCLUSION: These results
      indicate that 2% phenylephrine hydrochloride eye drop solutions were physically,
      chemically and microbiologically stable for at least 60 days when stored in type
      I amber glass vials at room temperature, allowing the compounding of higher batch
      sizes.

PMID- 25577015
TI  - [Effect of the microencapsulation process parameters piroxicam by complex
      coacervation].
AB  - INTRODUCTION: The gelatin-acacia system is used for the microencapsulation of
      piroxicam by complex coacervation. MATERIALS AND METHODS: The effect of some
      formulation parameters and process, namely the ratio of gelatin/gum acacia,
      core/wall ratio, concentration of crosslinking agent and crosslinking time are
      studied. The microcapsules properties are evaluated. RESULTS: The results showed
      that the microcapsules have a spherical shape, a coacervation efficiency greater
      than 70%, an average diameter less than 250 microns, a good stability and
      finally, the better values are obtained for gelatin/acacia ratio (5/3), ratio
      core/wall (1/4), an amount of 2 mL of crosslinking agent and a crosslinking time
      of 60 minutes.

PMID- 25577016
TI  - [Injectable preparation of labeled leucine with the carbon 13 for a clinical
      research program on the Alzheimer disease: pharmaceutical control of raw
      materials and the finished product and stability study].
AB  - INTRODUCTION: The L-leucine labeled (L-[U-(13)C] Leu) is a stable isotopic tracer
      administered by parenteral route within the framework of a new clinical research
      program concerning the diagnosis of the Alzheimer's disease. To meet regulatory
      requirements and have ready to use solution with an expiration date, a
      pharmaceutical control of raw materials and the finished product followed by a
      stability study were realised. MATERIALS AND METHOD: After the pharmaceutical
      control of raw materials, the solution of L-[U-(13)C] Leu was prepared according
      to the good practices preparation. Prepared bottles were stored for 1 year of a
      share in a climatic chamber (25  degrees C+/-2  degrees C) and the other in a
      refrigerator (5  degrees C+/-3  degrees C). To assess stability, the
      physicochemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C] Leu
      concentration, sodium concentration, isotopic enrichment) and microbiological
      (bacterial endotoxin and sterility) were performed at regular intervals for 1
      year. RESULTS: Neither significant decrease of L-[U-(13)C] Leu concentration and
      sodium concentration nor pH and osmolality variation were observed for 1 year.
      Isotopic enrichment higher than 99.9% reflected the stability of labelling of L
      leucine molecule. The sub-visible particles, the bacterial endotoxin and
      sterility were in accordance with the European pharmacopoeia attesting limpidity,
      apyrogenicity and sterility of this injectable preparation. DISCUSSION AND
      CONCLUSION: The injectable preparation of L-[U-(13)C] Leu was stable after 1 year
      for two preservation conditions, ensuring to safety for administration for human
      within the framework of this clinical research.

PMID- 25577017
TI  - Sarcopenia among hospitalized patients - A cross-sectional study.
AB  - BACKGROUND & AIMS: Data on the prevalence of sarcopenia among hospitalized older
      patients are scarce and there is no available information on the burden of
      sarcopenia among younger patients. The present study aims to increase the
      knowledge about the frequency of sarcopenia among hospitalized patients and to
      evaluate the influence of different diagnostic criteria in these estimates.
      METHODS: A cross-sectional study was conducted in hospitalized adult patients.
      Sarcopenia was defined, according to the European Working Group on Sarcopenia in
      Older People (EWGSOP), as the presence of both low muscle mass, assessed by
      Bioelectrical Impedance Analysis (BIA), adjusted for height, and low muscle
      function (hand grip strength). Two other criteria were applied, also using hand
      grip strength for evaluating muscle function, one that also assessed muscle mass
      by BIA, but adjusted for weight, and another which estimated muscle mass based on
      mid-arm muscle circumference. Nutritional status was evaluated by Patient
      Generated Subjective Global Assessment. The degree of agreement between the
      different diagnostic criteria was assessed using kappa. Multivariable logistic
      regression models were used in order to identify factors associated with
      sarcopenia. RESULTS: 608 hospitalized adult patients aged >=18 years composed the
      study sample. According to EWGSOP's criteria, 25.3% patients were sarcopenic.
      However, depending on age and on the applied criteria, frequency of sarcopenia
      varied from 5% to 41.1% for men and from 4.9% to 38.3% for women. There was 95.7%
      (k = 0.89) agreement between criteria that estimated muscle mass by BIA.
      According to EWGSOP criteria approximately 20% of the non-undernourished patients
      were sarcopenic. Furthermore, 29.5% of overweight and 18.7% of obese patients
      were sarcopenic. Factors associated with sarcopenia were male gender, age >=65
      years, moderate or severe dependence, being undernourished and admitted to a
      medical ward. CONCLUSIONS: Sarcopenia is frequent among hospitalized patients and
      varies widely depending on the applied diagnostic criteria. Sarcopenia was
      identified in a considerable proportion of patients aged under >=65 years and in
      non-undernourished, namely among overweight and obese.

PMID- 25577018
TI  - Proconsul heseloni distal radial and ulnar epiphyses from the Kaswanga Primate
      Site, Rusinga Island, Kenya.
AB  - Only two distal epiphyses of a radius and ulna are consensually attributed to the
      holotype skeleton of Proconsul heseloni, KNM-RU 2036. Here, we describe seven
      adult and immature distal antebrachial (radial and ulnar) epiphyses from two
      other individuals of P. heseloni from the Lower Miocene deposits of the Kaswanga
      Primate Site (KPS), Rusinga Island, Kenya. Because KNM-RU 2036 and KNM-KPS
      individuals III and VIII are conspecific and penecontemporaneous, their
      comparison provides the opportunity i) to characterize, for the first time, the
      morphological variation of the distal radioulnar joint in a Miocene ape, P.
      heseloni, and ii) to investigate the functional and evolutionary implications.
      Our results show that the distal antebrachial epiphyses of KNM-KPS III and VIII
      correspond to stages of bone maturation that are more advanced than those of KNM
      RU 2036 (larger articulations and sharper articular borders and ligament
      attachments that are more developed). Accordingly, functional interpretations
      based solely on the skeleton of KNM-RU 2036 have involved an underestimation of
      the forearm rotation abilities of P. heseloni. In particular, the KPS fossils do
      not exhibit the primitive morphology of distal radioulnar syndesmosis, as those
      of KNM-RU 2036 and most nonhominoid primates, but rather the morphology of an
      incipient diarthrosis (as in extant lorisines and hominoids). The distal
      radioulnar diarthrosis permits more mobility and maintenance of the wrist during
      repeated and slow rotation of the forearms, which facilitates any form of
      quadrupedal locomotion on discontinuous and variably oriented supports. By
      providing the oldest evidence of a distal radioulnar joint in an early Miocene
      hominoid, the main conclusions of this study are consistent with the role of
      cautious climbing as a prerequisite step for the emergence of positional
      adaptations in apes. 

PMID- 25577019
TI  - Archaeogenomic insights into the adaptation of plants to the human environment:
      pushing plant-hominin co-evolution back to the Pliocene.
AB  - The colonization of the human environment by plants, and the consequent evolution
      of domesticated forms is increasingly being viewed as a co-evolutionary plant
      human process that occurred over a long time period, with evidence for the co
      evolutionary relationship between plants and humans reaching ever deeper into the
      hominin past. This developing view is characterized by a change in emphasis on
      the drivers of evolution in the case of plants. Rather than individual species
      being passive recipients of artificial selection pressures and ultimately
      becoming domesticates, entire plant communities adapted to the human environment.
      This evolutionary scenario leads to systems level genetic expectations from
      models that can be explored through ancient DNA and Next Generation Sequencing
      approaches. Emerging evidence suggests that domesticated genomes fit well with
      these expectations, with periods of stable complex evolution characterized by
      large amounts of change associated with relatively small selective value,
      punctuated by periods in which changes in one-half of the plant-hominin
      relationship cause rapid, low-complexity adaptation in the other. A corollary of
      a single plant-hominin co-evolutionary process is that clues about the initiation
      of the domestication process may well lie deep within the hominin lineage. 

PMID- 25577020
TI  - The causes of cancer, revisited.

PMID- 25577021
TI  - Retrospective study on the occurrence of the feline lungworms Aelurostrongylus
      abstrusus and Troglostrongylus spp. in endemic areas of Italy.
AB  - Aelurostrongylus abstrusus is a metastrongyloid nematode infesting the
      respiratory system of domestic cats worldwide. Troglostrongylus brevior and
      Troglostrongylus subcrenatus, two lungworms thought to infest wild felids, have
      been found recently in domestic cats from Spain and Italy. These unexpected
      findings have raised doubts about the assumed past and present occurrence of
      Troglostrongylus spp., especially T. brevior, in domestic hosts and suggest that
      there may have been missed detection or misdiagnosis. The present retrospective
      study evaluated the presence of lungworms in cats from Italy with a diagnosis of
      respiratory parasitism or with compatible lung lesions from 2002 to 2013. Sixty
      eight samples of DNA and larvae from cats with a diagnosis of aelurostrongylosis,
      and 53 formalin-fixed paraffin-embedded lung samples from cats confirmed as
      lungworm infested or with compatible lesions, were investigated using two DNA
      based assays specific for A. abstrusus or T. brevior. All DNA and larval samples
      were positive for A. abstrusus and one was additionally positive for T. brevior.
      Most paraffin-embedded lung tissues were positive only for A. abstrusus, but two
      samples tested positive for both lungworms and one for T. brevior only. This
      study supports the major role of A. abstrusus in causing feline respiratory
      parasitism in endemic areas of Italy.

PMID- 25577022
TI  - Area of hock hair loss in dairy cows: risk factors and correlation with a
      categorical scale.
AB  - Data from 3691 dairy cows from 76 farms were used to investigate the risk factors
      associated with the area of hair loss over the lateral aspect of the hock and the
      correlation between the area of hair loss (as calculated using a hock map) and
      hock lesion scores determined using a pre-existing categorical scale. Six factors
      were associated with a greater area of hair loss, including cows with locomotion
      score 3, a cleanliness score (10/28 to 18/28), high daily milk yield (25.1-58.1
      kg), poor body condition score (1-1.5), duration of winter housing (>=41 days)
      and some combinations of cubicle base and bedding materials. Compared with cows
      housed in cubicles with a concrete base and whole straw or rape straw bedding,
      cows housed in cubicles with concrete bases with sand or chopped straw bedding
      had smaller areas of hair loss and cows housed on a mattress base with whole
      straw or rape straw bedding had larger areas of hair loss. Area of hair loss, as
      measured on hock maps, was not significantly different between cows with score 1
      (median 23.6 cm(2)) and score 2 (median 20.3 cm(2)) on the categorical scale for
      hock lesions. This suggests that the categorical scale was not reflecting the
      extent of hair loss and that hock maps are a good alternative for studying the
      dynamics of hock lesions over time. 

PMID- 25577023
TI  - Systematic review and meta-analysis of hydrocarbon exposure and the risk of
      Parkinson's disease.
AB  - BACKGROUND: There is no consensus on the association between exposure to
      hydrocarbons and the risk of Parkinson's disease (PD). We conducted a systematic
      review and meta-analysis to summarise the epidemiological evidence and included a
      new large case-control study. METHODS: Data were extracted following a predefined
      protocol. Risk estimates regarding the association between hydrocarbon exposure
      and PD were consolidated to produce a summary odds ratio (OR), 95% confidence
      intervals (CI), and p-value. In our case-control study, 1463 PD patients and 685
      controls were recruited from clinical trials and completed a structured
      questionnaire describing their previous working exposure to hydrocarbons and
      other demographic measures. The association between exposure to hydrocarbons and
      risk of PD was evaluated using logistic regression. RESULTS: The systematic
      search identified 13 case-control studies matching the inclusion criteria. The
      meta-analysis included 3020 PD cases and 6494 controls. The summary OR was 1.32
      (95% CI 1.08-1.62, p = 0.006) for hydrocarbon exposure (ever versus never). In
      the PD GEN study, occupational exposure to hydrocarbons significantly increased
      the risk of PD (OR = 1.61; 95% CI 1.10-2.36, p = 0.014), and risk dose
      dependently increased for subjects exposed greater than 10 years compared to
      subjects never exposed (OR = 2.19; 95% CI 1.13-4.26, p = 0.021). The addition of
      PD GEN data increased the total numbers to 4483 PD cases and 7179 controls and
      strengthened the significant association (summary OR = 1.36; 95% CI 1.13-1.63, p
      = 0.001). CONCLUSIONS: This systematic review supports a positive association
      between hydrocarbon exposure and PD. Data from prospective studies are required
      to reinforce the relationship between hydrocarbon exposure and PD.

PMID- 25577024
TI  - Long-term outcome of deep brain stimulation in fragile X-associated tremor/ataxia
      syndrome.
AB  - INTRODUCTION: Fragile X-associated tremor/ataxia syndrome (FXTAS) presents as
      complex movement disorder including tremor and cerebellar ataxia. The efficacy
      and safety of deep brain stimulation of the nucleus ventralis intermedius of the
      thalamus in atypical tremor syndromes like FXTAS remains to be determined.
      METHODS: Here, we report the long-term outcome of three male genetically
      confirmed FXTAS patients treated with bilateral neurostimulation of the nucleus
      ventralis intermedius for up to four years. RESULTS: All patients demonstrated
      sustained improvement of both tremor and ataxia - the latter included improvement
      of intention tremor and axial tremor. Kinematic gait analyses further
      demonstrated a regularization of the gait cycle. Initial improvements of hand
      functional disability were not sustained and reached the preoperative level of
      impairment within one to two years from surgery. CONCLUSION: Our data on patients
      with a genetic cause of tremor show favorable outcome and may contribute to
      improved patient stratification for neurostimulation therapy in the future.

PMID- 25577025
TI  - Severity of orthostatic hypotension in the course of Parkinson's disease: no
      correlation with the duration of the disease.
AB  - BACKGROUND: Orthostatic hypotension (OH) is a common issue in Parkinson's disease
      (PD), affecting about 30%-40% of PD patients. Symptoms of OH include
      lightheadedness, dizziness, postural instability, vertigo and blurred vision. OH
      considerably contributes to disease burden and reduced quality of life for PD
      patients. OBJECTIVE: To determine whether the severity of OH in PD advances
      significantly with the duration of the disease. METHODS: For 106 PD patients
      lying-to-standing orthostatic tests were performed to evaluate orthostasis.
      Severity of OH was measured as maximal drop of systolic blood pressure (SBP)
      after postural challenge, as the mean of three measurements. The relationship
      between the maximal drop of SBP and the duration of PD was tested applying ANOVA.
      Consecutively, 64 patients under regular ambulant supervision received
      appointments to evaluate their orthostasis repeatedly. From these patients a
      separate cohort was set up to investigate OH progression in the course of PD.
      RESULTS: The lack of a correlation between the severity of OH in PD and the
      duration of the disease was determined (p = 0.064). The long term analysis for
      the patients under regular ambulant supervision demonstrated that the severity of
      OH does not advance in the course of PD in a statistically significant manner (p
      = 0.83). CONCLUSIONS: OH does not appear to be a symptom only of the late stage
      of PD. The presence of OH along with early motor signs does not necessarily point
      to multiple system atrophy.

PMID- 25577026
TI  - Development of a psychosocial distress measure for Ugandan adolescents living
      with HIV.
AB  - Psychological distress among adolescents living with HIV (ALH) has been
      associated with risky behaviors including non-adherence to anti-retroviral
      therapy, leading to increased risk for AIDS morbidity and mortality. Efforts to
      establish the nature, prevalence, and impact of psychological distress among ALH
      in Uganda are hindered by the lack of culturally relevant assessment tools. The
      purpose of this study was to develop and test a measure for psychological
      distress for Ugandan ALH aged 12-19 years (N = 508; 53.1 % female). Using a mixed
      method approach, we developed and tested a 25-item checklist with six subscales
      anhedonia, depressive-anxiety, isolation, suicidal ideation, sleep problems, and
      somatization. We found adequate reliability for the scale (alpha = 0.89), and a
      satisfactory measurement structure in our confirmatory factor analyses (RMSEA
      <1.0, and CFI and TLI >0.90). We discuss the potential use of this culturally
      sensitive scale to examine psychological distress among ALH in Uganda. 

PMID- 25577027
TI  - Nonlinear analysis of tRNAs nucleotide sequences by random walks: randomness and
      order in the primitive informational polymers.
AB  - In order to test the hypothesis that the nucleotide sequences of the primitive
      informational polymers might not be chosen randomly and in the attempt to compare
      among taxa, we propose a comparison of computer-generated random sequences with
      tRNAs nucleotide sequences present in the bacterial and archaeal genomes, being
      tRNAs molecules possible "fossils" of the time (billions years ago) in which life
      arose. Our approach is based on the analysis of sequences of tRNAs described as
      random walks and the distances from the origin evaluated by the use of nonlinear
      indexes (largest Lyapunov exponent, entropy, BDS statistic). Six different tRNAs
      of Bacteria and Archaea (ten Archaea and ten Bacteria, thermophilic and
      mesophilic ones; n = 120), and computer-generated random sequences (n = 50) were
      studied. Our data show that tRNAs present indices statistical lower than the ones
      of computer-generated random data (tRNAs own a more ordered sequence than random
      ones: Lyapunov, p < 0.01; entropy, p < 0.05; BDS, p < 0.01). The observed
      deviation from pure randomness should be arisen from some constraints like the
      secondary structure of this biologic macromolecule and/or from a "frozen"
      stochastic transition, or even from the possible peculiar origin of tRNA by
      replication of older proto-RNA. Comparing between taxa, in the species studied,
      Bacteria present BDS and Base ratio (G+C)/(A+T) indexes statistically lower than
      in Archaea, together which a 20% of entropy increase. The analysis of a greater
      number of tRNAs and species will permit to explain if this finding, showing a
      higher randomness in the bacterial tRNAs sequences, is linked to the different
      base ratio, to the different environments in which the microorganisms live or to
      an evolutionary effect.

PMID- 25577028
TI  - Stereotactic radiotherapy for head neck cancer.

PMID- 25577029
TI  - Stapediovestibular dislocation depicted on temporal bone computed tomography with
      3D rendering.
AB  - Stapediovestibular dislocation is an unusual form of ossicular trauma. In this
      article, a case of medial stapediovestibular dislocation and pneumolabyrinth due
      to penetrating injury with a stick diagnosed on temporal bone CT is described. In
      particular, 3D CT renderings can aid in the evaluation of the displaced ossicles.

PMID- 25577030
TI  - Date-independent parameters: an innovative method to assess fetal cerebellar
      vermis.
AB  - The objectives of this paper were to identify gestational age-independent
      parameters for cerebellar vermis (CV) evaluation and examine their use in CV
      integrity assessments. Using three-dimensional ultrasonography, we obtained the
      following measurements from 217 pregnant women carrying 18-37-week-old fetuses:
      the largest area of the CV, vermal craniocaudal distance (VCC), vermal anterior
      to posterior diameter, and vermal perimeter (VP). In addition, fetal growth
      parameters (biparietal diameter, head circumference femoral length [FL], humeral
      length, transverse cerebellar diameter, and abdominal circumference) were
      evaluated. The ratios of the CV dimensions to each other and to the fetal growth
      parameters were calculated. Ratios showing no significant correlation with
      gestational age and acceptable internal validity in subsequent bootstrap analyses
      were chosen. The normal ranges of the specific parameters were compared with
      cases identified with posterior fossa anomalies (PFA). The ratios VP/FL (mean
      1.20, SD 0.09), VCC/FL (mean 0.36, SD 0.03), and VCC/VP (mean 0.3, SD 0.03) were
      chosen using our protocol. These parameters were not significantly different
      between normal fetuses and those with PFA and an intact vermis. However, VP/FL
      and VCC/FL values were abnormal in cases of hypoplastic vermis or vermian
      agenesis, while the VP/VCC value was abnormal only in cases of vermian agenesis.
      The VP/FL, VCC/FL, and VCC/VP ratios are gestational age-independent parameters
      in evaluation of CV integrity. 

PMID- 25577031
TI  - Intentional esophageal intubation to improve visualization during emergent
      endotracheal intubation in the context of massive vomiting: a case report.
AB  - Impaired visualization during intubation due to vomitus of gastric contents is a
      potential cause of failed intubation. An 82-year-old woman was intubated
      emergently for respiratory distress secondary to aspiration of gastric contents.
      Her intubation was hindered by the presence of a massive amount of ongoing
      vomitus that impaired visualization and overwhelmed all suction capabilities.
      Intentional blind intubation of the esophagus with an endotracheal tube was
      performed with successful diversion of ongoing vomitus away from the airway.
      Thereafter, after brief suctioning, the larynx was quickly visualized and the
      patient was successfully intubated. 

PMID- 25577032
TI  - Effect of hydroxyethyl starch 130/0.4 on ischemia-reperfusion determinants in
      minor lower extremity surgery with tourniquet application.
AB  - STUDY OBJECTIVE: To investigate the effect of 6% hydroxyethyl starch (HES)
      (130/0.4) infusion on ischemia-reperfusion determinants in minor lower extremity
      operations with tourniquet application. DESIGN: Prospective, randomized, clinical
      trial. SETTING: University hospital operation room. PATIENTS: American Society of
      Anesthesiologists I and II 40 patients between 18 and 65 years of age who were
      scheduled to undergo knee arthroscopy and below-knee minor orthopedic surgery.
      INTERVENTIONS: Patients were randomized into 2 groups (normal saline [NS] group
      and HES group). Unilateral spinal anesthesia with 2-mL 0.5% hyperbaric
      bupivacaine after 10 mL/kg NS intravenous infusion to NS group and 10 mL/kg 6%
      HES intravenous infusions to HES group. MAIN OUTCOME MEASURES: Blood samples were
      obtained from antecubital vein for malondialdehyde, xanthine oxidase, and
      hypoxanthine before tourniquet inflation and after 10 minutes of tourniquet
      deflation. RESULTS: There was no significant difference between groups with
      respect of hemodynamic data. There were no significant differences between 2
      groups in terms of malondialdehyde values before tourniquet inflation and after
      tourniquet deflation. In the HES group, xanthine oxidase levels after tourniquet
      deflation were significantly lower than xanthine oxidase levels before tourniquet
      inflation (P < .05). In the HES group, hypoxanthine levels after tourniquet
      deflation were similar with the basal levels; however, they were significantly
      higher than levels obtained before tourniquet inflation in the SF group (P <
      .05). CONCLUSION: HES infusion may be beneficial for reduction of tourniquet
      associated ischemia-reperfusion injury; however, further large-scale studies are
      needed to fully elucidate its mechanism.

PMID- 25577033
TI  - Development of a physiologically based pharmacokinetic model for a domain
      antibody in mice using the two-pore theory.
AB  - Domain antibodies (dAbs) are the smallest antigen-binding fragments of
      immunoglobulins. To date, there is limited insight into the pharmacokinetics of
      dAbs, especially their distribution into tissues and elimination. The objective
      of this work was to develop a physiologically-based pharmacokinetic model to
      investigate the biodisposition of a non-specific dAb construct in mice. Following
      a single IV administration of 10 mg/kg dummy dAb protein to twenty four female
      mice, frequent blood samples were collected and whole body lateral sections were
      analyzed by quantitative whole-body autoradiography. The model is based on the
      two-pore hypothesis of extravasation where organ-specific isogravimetric flow
      rates (Jorg,ISO) and permeability-surface area products (PSorg) are expressed as
      linear functions of the lymph flow rate (Jorg) and the kidney compartment is
      modified to account for glomerular filtration of dAb. As a result, only Jorg,
      glomerular filtration coefficient and the combined volume of Bowman's capsule,
      proximal and distal renal tubules and loop of Henle were optimized by fitting
      simultaneously all blood and organ data to the model. Our model captures the
      pharmacokinetic profiles of dAb in blood and all organs and shows that
      extravasation into interstitial space is a predominantly diffusion-driven
      process. The parameter values were estimated with good precision (%RMSE ~ 30) and
      low cross-correlation (R(2) < 0.2). We developed a flexible model with a limited
      parameter number that may be applied to other biotherapeutics after adapting for
      size-related effects on extravasation and renal elimination processes.

PMID- 25577034
TI  - Why Mothers and Young Children Agree or Disagree in Their Reports of the Child's
      Problem Behavior.
AB  - This study examined multiple determinants of discrepancies between mother and
      child reports of problem behavior. In 5,414 6-year-olds, child problem behavior
      was assessed by self-report using the Berkeley Puppet Interview and by maternal
      report using the Child Behavior Checklist. Patterns in mother-child reports were
      modeled using latent profile analysis. Four profiles, differing in problem level,
      and the direction and magnitude of mother-child discrepancies, were identified:
      one profile representing agreement (46%), another representing slight
      discrepancies (30%), and two representing higher problem levels and more
      discrepancies. In the latter two profiles either children (11%) or mothers (13%)
      reported more problems. Compared to the first profile, the second was
      predominantly characterized by a positive family environment, the third by child
      cognitive difficulties, and the fourth by harsh discipline and poor family
      functioning. Knowledge about specific child/family characteristics that
      contribute to mother-child discrepancies can help to interpret informants'
      reports and to make diagnostic decisions.

PMID- 25577035
TI  - Prediction and interpretation of the lipophilicity of small peptides.
AB  - Peptide-based drug discovery has considerably expanded and solid in silico tools
      for the prediction of physico-chemical properties of peptides are urgently
      needed. In this work we tested some combinations of descriptors/algorithms to
      find the best model to predict [Formula: see text] of a series of peptides. To do
      that we evaluate the models statistical performances but also their skills in
      providing a reliable deconvolution of the balance of intermolecular forces
      governing the partitioning phenomenon. Results prove that a PLS model based on
      VolSurf+ descriptors is the best tool to predict [Formula: see text] of neutral
      and ionised peptides. The mechanistic interpretation also reveals that the
      inclusion in the chemical structure of a HBD group is more efficient in
      decreasing lipophilicity than the inclusion of a HBA group. 

PMID- 25577036
TI  - Vaginal group B streptococcus status during intrapartum antibiotic prophylaxis.
AB  - OBJECTIVE: To assess maternal group B streptococcus (GBS) colonization status and
      the pharmacokinetic profile of penicillin G in the umbilical cord and amniotic
      fluid compartment during 4 hours of intrapartum antibiotic prophylaxis (IAP).
      METHODS: In a prospective study at a hospital in Montevideo, Uruguay, 60 GBS
      carriers in active labor after a singleton pregnancy of 37 weeks or more were
      enrolled between April 1, 2011, and April 30, 2012. Intravenous penicillin G was
      administered via a standard regimen. Rectovaginal samples were obtained before
      IAP initiation, and 2 and 4 hours after the initial dose. Penicillin G
      concentrations were measured by high-performance liquid chromatography. Samples
      were obtained from fetal cord blood in all cases and from amniotic fluid obtained
      from patients who delivered by cesarean. RESULTS: Among the 60 participants, 43
      (72%) had a positive rectovaginal sample before IAP initiation. Of these women,
      23 (53%) had negative cultures after 2 hours; after 4 hours, only 5 (12%)
      remained positive for GBS. The penicillin G concentration in amniotic fluid and
      cord blood was above the minimum inhibitory concentration (0.12 MUg/mL) in all
      cases. CONCLUSION: Four hours of IAP was needed to reduce the number of women
      with positive GBS cultures to 12%. Therefore, 4 hours of IAP might be necessary
      to achieve overall effectiveness from this treatment.

PMID- 25577037
TI  - Dual receptor-targeting 99mTc-labeled Arg-Gly-Asp-conjugated Alpha-Melanocyte
      stimulating hormone hybrid peptides for human melanoma imaging.
AB  - INTRODUCTION: The aim of this study was to examine whether the substitution of
      the Lys linker with the aminooctanoic acid (Aoc) and polyethylene glycol (PEG)
      linker could substantially decrease the non-specific renal uptake of (99m)Tc
      labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone (alpha-MSH)
      hybrid peptides. METHODS: The RGD motif {Arg-Gly-Asp-DTyr-Asp} was coupled to
      [Cys(3,4,10), D-Phe(7), Arg(11)]alpha-MSH3-13 via the Aoc or PEG2 linker to
      generate RGD-Aoc-(Arg(11))CCMSH and RGD-PEG-(Arg(11))CCMSH. The biodistribution
      results of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG2-(Arg(11))CCMSH
      were examined in M21 human melanoma-xenografted nude mice. RESULTS: The
      substitution of Lys linker with Aoc and PEG2 linker significantly reduced the
      renal uptake of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG2
      (Arg(11))CCMSH by 58% and 63% at 2h post-injection. The renal uptake of (99m)Tc
      RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG2-(Arg(11))CCMSH was 27.93 +/- 3.98 and
      22.01 +/- 9.89% ID/g at 2 h post-injection. (99m)Tc-RGD-Aoc-(Arg(11))CCMSH
      displayed higher tumor uptake than (99m)Tc-RGD-PEG2-(Arg(11))CCMSH (2.35 +/- 0.12
      vs. 1.71 +/- 0.25% ID/g at 2 h post-injection). The M21 human melanoma lesions
      could be clearly visualized by SPECT/CT using (99m)Tc-RGD-Aoc-(Arg(11))CCMSH as
      an imaging probe. CONCLUSIONS: The favorable effect of Aoc and PEG2 linker in
      reducing the renal uptake provided a new insight into the design of novel dual
      receptor-targeting radiolabeled peptides.

PMID- 25577038
TI  - Radiolabeled antibodies in prostate cancer: a case study showing the effect of
      host immunity on antibody bio-distribution.
AB  - OBJECTIVES: Human tumors xenografted in immunodeficient mice are crucial models
      in nuclear medicine to evaluate the effectiveness of candidate diagnostic and
      therapeutic compounds. However, little attention has been focused on the
      biological profile of the host model and its potential effects on the bio
      distribution and tumor targeting of the tracer compound under study. We
      specifically investigated the dissimilarity in bio-distribution of (111)In-DTPA
      5A10, which targets free prostate specific antigen (fPSA), in two animal models.
      METHODS: In vivo bio-distribution studies of (111)In-DTPA-5A10 were performed in
      immunodeficient BALB/c-nu or NMRI-nu mice with subcutaneous (s.c.) LNCaP tumors.
      Targeting-specificity of the tracer was assessed by quantifying the uptake in (a)
      mice with s.c. xenografts of PSA-negative DU145 cells as well as (b) BALB/c-nu or
      NMRI-nu mice co-injected with an excess of non-labeled 5A10. Finally, the effect
      of neonatal Fc-receptor (FcRn) inhibition on the bio-distribution of the
      conjugate was studied by saturating FcRn-binding capacity with nonspecific IgG1.
      RESULTS: The inherent biological attributes of the mouse model substantially
      influenced the bio-distribution and pharmacokinetics of (111)In-DTPA-5A10. With
      LNCaP xenografts in BALB/c-nu mice (with intact B and NK cells but with deficient
      T cells) versus NMRI-nu mice (with intact B cells, increased NK cells and absent
      T cells), we observed a significantly higher hepatic accumulation (26 +/- 3.9
      versus 3.5 +/- 0.4%IA/g respectively), and concomitantly lower tumor uptake (25
      +/- 11 versus 52 +/- 10%IA/g respectively) in BALB/c-nu mice. Inhibiting FcRn by
      administration of nonspecific IgG1 just prior to (111)In-DTPA-5A10 did not change
      tumor accumulation significantly. CONCLUSIONS: We demonstrated that the choice of
      immunodeficient mouse model importantly influence the bio-distribution of (111)In
      DTPA-5A10. This study further highlighted important considerations in the
      evaluation of preclinical tracers, with respect to gaining information on their
      performance in the translational setting. Investigators utilizing xenograft
      models need to assess not only radiolabeling strategies, but also the host
      immunological status.

PMID- 25577040
TI  - Discovery of piperidine ethers as selective orexin receptor antagonists (SORAs)
      inspired by filorexant.
AB  - Highly selective orexin receptor antagonists (SORAs) of the orexin 2 receptor
      (OX2R) have become attractive targets both as potential therapeutics for insomnia
      as well as biological tools to help further elucidate the underlying pharmacology
      of the orexin signaling pathway. Herein, we describe the discovery of a novel
      piperidine ether 2-SORA class identified by systematic lead optimization
      beginning with filorexant, a dual orexin receptor antagonist (DORA) that recently
      completed Phase 2 clinical trials. Changes to the ether linkage and pendant
      heterocycle of filorexant were found to impart significant selectivity for OX2R,
      culminating in lead compound PE-6. PE-6 displays sub-nanomolar binding affinity
      and functional potency on OX2R while maintaining >1600-fold binding selectivity
      and >200-fold functional selectivity versus the orexin 1 receptor (OX1R). PE-6
      bears a clean off-target profile, a good overall preclinical pharmacokinetic (PK)
      profile, and reduces wakefulness with increased NREM and REM sleep when evaluated
      in vivo in a rat sleep study. Importantly, subtle structural changes to the
      piperidine ether class impart dramatic changes in receptor selectivity. To this
      end, our laboratories have identified multiple piperidine ether 2-SORAs, 1-SORAs,
      and DORAs, providing access to a number of important biological tool compounds
      from a single structural class. 

PMID- 25577039
TI  - Synthesis and evaluation of NS5A inhibitors containing diverse heteroaromatic
      cores.
AB  - Inhibitors of the HCV NS5A nonstructural protein are showing promising clinical
      potential in the treatment of hepatitis C when used in combination with other
      direct-acting antiviral agents. Current NS5A clinical candidates such as
      daclatasvir, ledipasvir, and ombitasvir share a common pharmacophore that
      features a pair of (S)-methoxycarbonylvaline capped pyrrolidines linked to
      various cores by amides, imidazoles and/or benzimidazoles. In this Letter, we
      describe the evaluation of NS5A inhibitors which contain alternative
      heteroaromatic replacements for these amide mimetics. The SAR knowledge gleaned
      in the optimization of scaffolds containing benzoxazoles was parlayed toward the
      identification of potent NS5A inhibitors containing other heteroaromatic
      replacements such as indoles and imidazopyridines. 

PMID- 25577041
TI  - Benzimidazole-containing HCV NS5A inhibitors: effect of 4-substituted
      pyrrolidines in balancing genotype 1a and 1b potency.
AB  - The treatment of HCV with highly efficacious, well-tolerated, interferon-free
      regimens is a compelling clinical goal. Trials employing combinations of direct
      acting antivirals that include NS5A inhibitors have shown significant promise in
      meeting this challenge. Herein, we describe our efforts to identify inhibitors of
      NS5A and report on the discovery of benzimidazole-containing analogs with
      subnanomolar potency against genotype 1a and 1b replicons. Our SAR exploration of
      4-substituted pyrrolidines revealed that the subtle inclusion of a 4-methyl group
      could profoundly increase genotype 1a potency in multiple scaffold classes. 

PMID- 25577042
TI  - Predicting the impact of adverse events and treatment duration on medical
      resource utilization-related costs in hepatitis C genotype 1 treatment-naive
      patients receiving antiviral therapy.
AB  - OBJECTIVES: Studies on medical resource utilization (MRU) and related costs are
      important for evaluating the potential patient management and cost-effectiveness
      implications of antiviral treatments for hepatitis C virus (HCV) infection. The
      objectives of this study were (i) to compare the MRU and related costs for two
      treatment approaches; (ii) to identify the main drivers of resource use and
      costs; and (iii) to assess the effects of various treatment regimen attributes on
      MRU-related costs in a UK clinical setting. METHODS: The analysis used data
      collected alongside the simeprevir (SMV) phase III trials for treatment-naive
      genotype 1 HCV-infected patients; these data covered outpatient consultations
      with specialists, emergency room visits and hospital admissions. Logistic
      regressions were constructed to estimate the predictors of resource utilization,
      and a two-part multivariable analysis model was used to determine the total costs
      of treatment in the UK. RESULTS: Data on 731 patients receiving SMV plus
      pegylated interferon and ribavirin (SMV/PegIFN/R) or PegIFN/R were included in
      the analysis. While MRU was similar between the SMV and PegIFN/R groups, MRU
      related costs were significantly lower in the SMV group than in the PegIFN/R
      group (P < 0.05). High body mass index (P < 0.05), severe fibrosis (P < 0.05),
      shortened treatment duration to 24 weeks (P < 0.05), and anaemia and rash during
      treatment (P < 0.001) were identified as predictors of hospitalization and
      outpatient visits and as drivers of total costs. Univariate sensitivity analyses
      suggested that shortened treatment duration and lower occurrence of rash lead to
      large cost savings. CONCLUSION: This study identified both baseline and on
      treatment antiviral therapy characteristics as drivers of MRU-related costs for
      HCV patients following antiviral therapy. The shortened treatment duration and
      reduction in rash due to treatment with SMV triple therapy lead to substantial
      non-drug cost savings, compared with PegIFN/R treatment. This suggests that there
      are potential patient management and cost-effectiveness implications associated
      with the choice of specific antiviral treatments.

PMID- 25577043
TI  - Authentication of beef versus horse meat using 60 MHz 1H NMR spectroscopy.
AB  - This work reports a candidate screening protocol to distinguish beef from horse
      meat based upon comparison of triglyceride signatures obtained by 60 MHz (1)H NMR
      spectroscopy. Using a simple chloroform-based extraction, we obtained classic low
      field triglyceride spectra from typically a 10 min acquisition time. Peak
      integration was sufficient to differentiate samples of fresh beef (76
      extractions) and horse (62 extractions) using Naive Bayes classification.
      Principal component analysis gave a two-dimensional "authentic" beef region
      (p=0.001) against which further spectra could be compared. This model was
      challenged using a subset of 23 freeze-thawed training samples. The outcomes
      indicated that storing samples by freezing does not adversely affect the
      analysis. Of a further collection of extractions from previously unseen samples,
      90/91 beef spectra were classified as authentic, and 16/16 horse spectra as non
      authentic. We conclude that 60 MHz (1)H NMR represents a feasible high-throughput
      approach for screening raw meat.

PMID- 25577044
TI  - Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) in eel, trout, and barbel
      from the River Roya, Northern Italy.
AB  - Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) contribute to the dietary
      intake of total PCBs. They are consumed via ingestion of contaminated fish and
      fishery products. Thus, it is important to quantify their levels in aquatic
      organisms in order to evaluate the risks associated with fish consumption by
      humans. In 2013, an advisory against consumption of fish from the River Roya (IT)
      was disseminated after NDL PCBs were found to exceed maximum levels set by EU
      Regulations. We investigated the presence of NDL PCBs in eel, trout and barbel
      from the River Roya. We found concentrations in the range of 9.2-27.6 ng g(
      )(1)ww in barbel, 9.2-97.0 ng g(-1)ww in trout and 9.0-239.5 ng g(-1)ww in eel.
      The distribution of congeners among different species did not show significant
      variations and was characterized by a higher proportion of 153, 138 and 180
      congeners, according to their high resistance to metabolic degradation.

PMID- 25577045
TI  - Behaviour of liposomes loaded with bovine serum albumin during in vitro
      digestion.
AB  - This study examined the stability of liposomes loaded with negatively charged
      protein (bovine serum albumin, BSA) during in vitro digestion. Zeta-potential and
      morphology measurements confirmed that BSA-loaded liposomes were successfully
      prepared, with an encapsulation efficiency of around 34%. The encapsulated BSA
      and the integrity of the liposomes remained unchanged with time when the
      liposomes were digested in a simulated gastric environment, suggesting that the
      liposomal membrane protected the entrapped BSA from pepsin hydrolysis. BSA-loaded
      liposomes exhibited lower stability in simulated intestinal fluid, as shown by
      damaged membranes and the release of free fatty acids. Also, lipolysis kinetics
      revealed that bile salts and ionic strength could facilitate a high level of free
      fatty acid release. This work further supplemented our knowledge about the
      effects of gastrointestinal digestion conditions on liposomal properties and
      provided valuable information for the design of liposome formulations for the
      food and health care industries. 

PMID- 25577046
TI  - Monitoring peroxides generation during model wine fermentation by FOX-1 assay.
AB  - The quality of wine is mainly determined during the alcoholic fermentation that
      gradually transforms the grape juice into wine. Along this process the yeast goes
      through several stressful stages which can affect its fermentative ability and
      industrial performance, affecting wine quality. Based on their actual application
      on industrial winemaking, commercial Saccharomyces cerevisiae strains (EC1118,
      QA23, VIN7 and VL3) were used. They were inoculated in batch laboratory
      fermentations in a model wine solution for evaluating the production of reactive
      oxygen species (ROS) during the yeast's alcoholic fermentation. For first time
      total hydroperoxides were determined by FOX-1 assay to follow ROS generation. The
      total hydroperoxides accumulated along the 10 days of fermentation peaked up to
      10.0 MUM in yeast EC1118, of which 1.3 MUM was hydrogen peroxide (H2O2). The FOX
      1 based analytical approach herein presented is a valuable tool for the
      quantification of ROS oxidative damage during winemaking.

PMID- 25577047
TI  - Determination of dansylated amino acids and biogenic amines in Cannonau and
      Vermentino wines by HPLC-FLD.
AB  - Free amino acids (AA) and biogenic amines (BA) were quantified for the first time
      in Cannonau and Vermentino wines, the two most popular "Controlled Designation of
      Origin" wines from Sardinia (Italy). An analytical method for the simultaneous
      determination of AA and BA was developed, using selective derivatization with
      dansyl chloride followed by HPLC with fluorescence detection. Thirty-two
      compounds were identified in the wines analysed. High levels of AA were found,
      with proline being the most abundant with average levels of 1244 +/- 398 and 1008
      +/- 281 mg/L in Cannonau and Vermentino wines, respectively. BA were detected at
      average concentrations <10mg/L, except putrescine which reached 20.5 +/- 10.2mg/L
      in Cannonau wines. Histamine was never detected in any Vermentino wines. gamma
      Aminobutyric acid, 4-hydroxyproline, glycine, leucine+isoleucine and putrescine
      proved to be useful for differentiating Cannonau wines from Vermentino wines.

PMID- 25577048
TI  - Characterisation of cell-wall polysaccharides from mandarin segment membranes.
AB  - In an attempt to develop a process of enzymatic peeling of mandarin segments
      suitable for use on an industrial scale, the cell wall fraction of the segment
      membrane of Satsuma mandarin fruits was extracted to obtain a chelating agent
      soluble pectin fraction (ChSS), a dilute sodium hydroxide-soluble pectin fraction
      (DASS), a 1M sodium hydroxide-soluble hemicellulose fraction (1MASS), a 4M sodium
      hydroxide-soluble hemicellulose fraction (4MASS) and a cellulose-rich residue
      (3.1, 0.9, 0.4, 0.7 and 1.6%w/w of fresh membrane, respectively). The ChSS pectin
      consisted mainly of galacturonic acid followed by arabinose and galactose. The
      DASS fraction contained less galacturonic acid and more neutral sugars than ChSS.
      Eighty-nine percent of the galacturonic acid present in the segment membranes was
      recovered in the above two pectin fractions. The two hemicellulosic fractions
      consisted of two different molecular weight populations, which also differed in
      their sugar composition. Arabinose, xylose, mannose, galactose and glucose were
      the main sugar constituents of these hemicellulose fractions. In addition to an
      (arabino)xylan and a xyloglucan, the presence of an arabinogalactan is suggested
      by the sugar composition of both hemicelluloses. The pectin fractions were also
      characterised by their degradability by the pectic enzymes polygalacturonase,
      pectinmethylesterase and rhamnogalacturonan hydrolase. However the degree of
      degradation of the pectin fractions by enzymes differed, and the amount of the
      polymeric materials resistant to further degradation and the oligomeric products
      also differed. Using pectic enzymes it is possible to obtain peeled mandarin
      segments ready to eat or for canning. 

PMID- 25577049
TI  - Cooking quality and starch digestibility of gluten free pasta using new bean
      flour.
AB  - The use of rice/leguminous blend may be nutritionally convenient in gluten free
      product manufacturing. Gluten free spaghetti was prepared with rice flour and
      different concentrations of bean flour (included at levels of 0%, 20% and 40%,
      w/w) derived from a new developed white-seeded low phytic acid and lectin free
      (ws+lpa+lf) bean cultivar. Protein, ash and dietary fibre contents increased
      linearly (P<0.05) while total starch decreased quadratically (P<0.05) with the
      inclusion of ws+lpa+lf bean flour. The colour of spaghetti was influenced
      (P<0.05) by ws+lpa+lf bean inclusion. With respect to 0% spaghetti, the inclusion
      of ws+lpa+lf bean increased linearly (P<0.05) the optimal cooking time and the
      water absorption capacity, without affecting cooking loss and texture properties.
      The ws+lpa+lf bean inclusion increases quadratically (P<0.05) the resistant
      starch content, while decreasing quadratically (P<0.05) the in vitro glycemic
      index. The partial replacement of rice flour with bean flour can favourably be
      used in gluten free spaghetti formulation. 

PMID- 25577050
TI  - Changes in physicochemical characteristics and free amino acids of hawthorn
      (Crataegus pinnatifida) fruits during maturation.
AB  - In this study, changes in physicochemical characteristics associated with fruit
      quality and free amino acids were investigated during maturation of hawthorn
      fruits. Significant differences in these parameters were found during maturation.
      The color turned progressively from mature green to semi-red, to reach bright
      red; the shape changed gradually from oval to round or approached round; the
      size, weight, and edible part (flesh/core ratio) of hawthorns increased while the
      density of intact fruits did not change. The content of moisture, total soluble
      sugars, soluble pectin, reduced ascorbic acid, total ascorbic acid, fructose, and
      sucrose increased while crude protein content decreased significantly. The levels
      of starch, sucrose, titratable acidity, protopectin, pectin, total free amino
      acids, and total essential amino acids initially increased and then decreased
      gradually during maturation. The outcomes of this study provide additional and
      useful information for fresh consumption and processing as well as utilization of
      dropped unripe hawthorn fruits. 

PMID- 25577051
TI  - Liquid chromatography-electrospray ionization tandem mass spectrometry and
      dynamic multiple reaction monitoring method for determining multiple pesticide
      residues in tomato.
AB  - A quick and sensitive liquid chromatography-electrospray ionization tandem mass
      spectrometry method, using dynamic multiple reaction monitoring and a 1.8-MUm
      particle size analytical column, was developed to determine 57 pesticides in
      tomato in a 13-min run. QuEChERS (quick, easy, cheap, effective, rugged, and
      safe) method for samples preparations and validations was carried out in
      compliance with EU SANCO guidelines. The method was applied to 58 tomato samples.
      More than 84% of the compounds investigated showed limits of detection equal to
      or lower than 5 mg kg(-1). A mild (<20%), medium (20-50%), and strong (>50%)
      matrix effect was observed for 72%, 25%, and 3% of the pesticides studied,
      respectively. Eighty-one percent of the pesticides showed recoveries ranging
      between 70% and 120%. Twelve pesticides were detected in 35 samples, all below
      the maximum residue levels permitted in the Brazilian legislation; 15 samples
      exceeded the maximum residue levels established by the EU legislation for
      methamidophos; and 10 exceeded limits for acephate and four for bromuconazole.

PMID- 25577052
TI  - Analyzing a dipeptide library to identify human dipeptidyl peptidase IV
      inhibitor.
AB  - Human dipeptidyl peptidase IV (hDPPIV) inhibitors provide an effective strategy
      for the treatment of type 2 diabetes. Because certain peptides are known to act
      as hDPPIV inhibitors, a dataset of possible peptides with their inhibition
      intensities will facilitate the development of functional food for type 2
      diabetes. In this study, we examined a total of 337 dipeptides with respect to
      their hDPPIV inhibitory effects. Amino acid residues at N-termini dominated their
      inhibition intensities. Particularly highly inhibitory dipeptides discovered
      included the following novel dipeptides: Thr-His, Asn-His, Val-Leu, Met-Leu, and
      Met-Met. Using our dataset, prime candidates contributing to the hDPPIV
      inhibitory effect of soy protein hydrolyzates were successfully identified.
      Possible dietary proteins potentially able to produce particularly highly hDPPIV
      inhibitory peptides are also discussed on the basis of the dataset. 

PMID- 25577054
TI  - Determination of halosulfuron-methyl herbicide in sugarcane juice and tomato by
      capillary electrophoresis-tandem mass spectrometry.
AB  - A capillary electrophoresis-tandem mass spectrometry (CE-MS/MS) method for the
      determination of halosulfuron-methyl (HSU) residue in samples of sugarcane juice
      and tomato is introduced and validated. The samples were submitted to a QuEChERS
      extraction procedure followed by electrophoretic separation in NH4HCO3
      electrolyte (adjusted to pH 8.5) and detection by electrospray-tandem mass
      spectrometry. The total HSU migration took place in less than 3.5 min, and the
      detection was accomplished by monitoring three fragmentation processes of this
      anion: m/z 435-182, 139, and 83. The R(2) values for concentrations up to 100 ppb
      (MUg kg(-1)) were, respectively, 0.992, 0.992, and 0.978. Recovery values for
      samples spiked at three concentration levels (10, 20 and 50 ppb) were in the
      range of 96-104% with standard deviation not greater than 5.0%. The limit of
      detection for HSU in sugarcane juice and tomato was 2 ppb for both samples.

PMID- 25577053
TI  - Extraction, purification and identification of antifreeze proteins from cold
      acclimated malting barley (Hordeum vulgare L.).
AB  - Antifreeze proteins from cold-acclimated malting barley were extracted by
      infiltration-centrifugation. The infiltration time was optimised, and its
      extraction effect was evaluated. The effect of cold acclimation on the
      accumulation of barley antifreeze proteins (BaAFPs) was assessed by comparing the
      thermal hysteresis activities (THA) of proteins extracted from both cold
      acclimated and non-cold acclimated barley grain. Ultra-filtration, ammonium
      precipitation and column chromatography were used successively to purify the
      BaAFPs, and MALDI-TOF-MS/MS was used for protein identification. The results
      showed that infiltration-centrifugation was more targeted than the traditional
      method, and 10h was the optimal infiltration time. THA was observed only after
      cold acclimation implied that AFPs only began to accumulate after cold
      acclimation. After purification, BaAFP-I was obtained at an electrophoresis level
      and its THA was 1.04 degrees C (18.0 mg ml(-1)). The mass fingerprinting and
      sequencing results indicated the homology of the BaAFP-I to alpha-amylase
      inhibitor BDAI-1 (Hordeum vulgare).

PMID- 25577055
TI  - Detecting quinoxaline-2-carboxylic acid in animal tissues by using sensitive
      rapid enzyme-linked immunosorbent assay and time-resolved fluoroimmunoassay.
AB  - An indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and time
      resolved fluoroimmunoassay (TR-FIA) based on an anti-N-butylquinoxaline-2
      carboxamide (BQCA) monoclonal antibody were standardized and validated for
      quinoxaline-2-carboxylic acid (QCA) screening in animal tissues and its
      performance were compared to HPLC. The sensitivities obtained for edible tissue
      extracts were 1.62 and 1.12 ng ml(-1) for ic-ELISA and TR-FIA detection,
      respectively. Two samples were spiked with QCA and analyzed by both methods. The
      recovery values ranged from 92.6% to 112.2% and the coefficients of variation
      were less than 15% for QCA spiking into swine tissue samples at concentrations of
      2.5-50.0 MUg kg(-1). Excellent correlations (r(2)=0.987-0.996) of the ic
      ELISA/HPLC and TR-FIA/HPLC data were observed for processed samples. The results
      demonstrated that the ic-ELISA and TR-FIA methods were rapid and accurate for the
      residue detection of QCA in animal tissues.

PMID- 25577056
TI  - Mechanism of reactive carbonyl species trapping by hydroxytyrosol under simulated
      physiological conditions.
AB  - This investigation reveals that hydroxytyrosol (HT) could compete with lysine,
      arginine and histidine to bind methylglyoxal (MGO) and reducing the formation of
      advanced glycation end products. Kinetic of the degradation of HT in
      presence/absence of MGO under simulated physiological conditions is monitored by
      HPLC coupled to a QTOF spectrometer. HT should previously be oxidized to DOPAC
      (3,4-dihydroxyphenylacetic acid) which reacts with MGO by electrophilic aromatic
      substitution of the ortho-diphenyl ring. DOPAC was detected as the major
      degradation product of HT under simulated physiological conditions. Ortho
      hydroxyl groups are necessary to promote the nucleophilic addition of MGO by HT
      and related compounds. The formation of four adducts were described by mass
      spectrometry, but monoDOPAC-monoMGO adduct (C11H12O6) was predominant. Results
      suggest that HT and its degradation product DOPAC could have a relevant role in
      preventing the formation of advanced glycation end products and therefore
      potentially mitigate the diabetic complications. 

PMID- 25577057
TI  - Comparison of UPLC and HPLC methods for determination of vitamin C.
AB  - Ultra performance liquid chromatography (UPLC) and high-performance liquid
      chromatography (HPLC) methods for determination of ascorbic acid (AA) and total
      AA (TAA) contents (as the sum of AA and dehydroascorbic acid (DHAA) after its
      reduction to AA) in fruit beverages and in pharmaceutical preparations were
      compared. Both methods are rapid: total time of analysis was 15 and 6 min for
      HPLC and UPLC methods, respectively. The methods were validated in terms of
      linearity, instrument precision, limits of detection (LOD) and quantification
      (LOQ), accuracy and recovery. Intra- and inter-day instrument precisions for
      fruit juices, expressed as RSD, were 2.2% and 2.4% for HPLC, respectively, and
      1.7% and 1.9% for UPLC, respectively. For vitamin C tablets, inter- and intra-day
      precisions were 0.4% and 0.5%, respectively (HPLC), and 0.5% and 0.3%,
      respectively (UPLC). Both methods were sensitive: LOD was 0.049 MUg/mL for HPLC
      and 0.024 MUg/mL for UPLC while LOQs were 0.149 and 0.073 MUg/mL for HPLC and
      UPLC, respectively. These methods could be useful in the routine qualitative and
      quantitative analysis of AA or TAA in pharmaceutical preparations or fruit
      beverages. However, UPLC method is more sensitive, faster and consumes less
      eluent.

PMID- 25577058
TI  - Antioxidant components of Viburnum opulus L. determined by on-line HPLC-UV-ABTS
      radical scavenging and LC-UV-ESI-MS methods.
AB  - Antioxidant activity of the juice and seed and skin extracts prepared with
      methanol, acetonitrile, and water of Viburnum opulus L. grown in Eastern Black
      Sea Region were studied with an on-line HPLC-ABTS method and off-line antioxidant
      methods, among which a linear positive correlation was observed. The fruit
      extracts were analysed with the HPLC-UV method optimised with 14 standard
      phenolics. Identification of the phenolic components in the juice was made using
      an HPLC-UV-ESI-MS method. Nineteen phenolic compounds in juice were identified by
      comparing the retention times and mass spectra with those of the standards and
      the phenolics reported in the literature. The major peaks in the juice belonged
      to coumaroyl-quinic acid, chlorogenic acid, procyanidin B2, and procyanidin
      trimer. Quite different antioxidant composition profiles were obtained from the
      extracts with the solvents of different polarities. The antioxidant activities of
      the seed extracts were higher than those of the skin extracts in general. 

PMID- 25577059
TI  - Pulsed electric field (PEF)-induced aggregation between lysozyme, ovalbumin and
      ovotransferrin in multi-protein system.
AB  - The aggregation of multi-proteins is of great interest in food processing and a
      good understanding of the formation of aggregates during PEF processing is needed
      for the application of the process to pasteurize protein-based foods. The
      aggregates formation of a multi-protein system (containing ovalbumin,
      ovotransferrin and lysozyme) was studied through turbidity, size exclusion
      chromatography and SDS-PAGE patterns for interaction studies and binding forces.
      Results from size exclusion chromatography indicated that there was no soluble
      aggregates formed during PEF processing. The existence of lysozyme was important
      to form insoluble aggregates in the chosen ovalbumin solution. The results of SDS
      PAGE patterns indicated that lysozyme was prone to precipitate, and was
      relatively the higher component of aggregates. Citric acid could be effective in
      inhibiting lysozyme from interacting with other proteins during PEF processing.
      Blocking the free sulphydryl by N-ethylmaleimide (NEM) did not affect aggregation
      inhibition. 

PMID- 25577060
TI  - Influence of pig rennet on proteolysis, organic acids content and microbiota of
      Pecorino di Farindola, a traditional Italian ewe's raw milk cheese.
AB  - The use of pig rennet is very ancient and in Italy is only applied in the
      manufacture of Pecorino di Farindola cheese. In order to evaluate the key role of
      this rennet in the establishment of peculiar features of Pecorino di Farindola,
      cheeses made from raw ewes' milk using calf (A) and kid (B) rennets were compared
      to those produced with pig (C) rennet. The use of pig rennet for Pecorino di
      Farindola cheese making confers physico-chemical and proteolytic characteristics
      that differentiate it from cheeses produced with other coagulants. However, no
      microbiological differences were observed. Chesses made with pig and kid rennets
      were characterised by higher proteolysis after 7 days of ripening. The content of
      isovaleric and propionic acids at the end of ripening was correlated with the
      presence of propionibacteria.

PMID- 25577061
TI  - Neural networks applied to discriminate botanical origin of honeys.
AB  - The aim of this work is develop a tool based on neural networks to predict the
      botanical origin of honeys using physical and chemical parameters. The managed
      database consists of 49 honey samples of 2 different classes: monofloral (almond,
      holm oak, sweet chestnut, eucalyptus, orange, rosemary, lavender, strawberry
      trees, thyme, heather, sunflower) and multifloral. The moisture content,
      electrical conductivity, water activity, ashes content, pH, free acidity,
      colorimetric coordinates in CIELAB space (L(*), a(*), b(*)) and total phenols
      content of the honey samples were evaluated. Those properties were considered as
      input variables of the predictive model. The neural network is optimised through
      several tests with different numbers of neurons in the hidden layer and also with
      different input variables. The reduced error rates (5%) allow us to conclude that
      the botanical origin of honey can be reliably and quickly known from the
      colorimetric information and the electrical conductivity of honey. 

PMID- 25577062
TI  - Thermodynamics of the interaction of the food additive tartrazine with serum
      albumins: a microcalorimetric investigation.
AB  - The thermodynamics of the interaction of the food colourant tartrazine with two
      homologous serum proteins, HSA and BSA, were investigated, employing
      microcalorimetric techniques. At T=298.15K the equilibrium constants for the
      tartrazine-BSA and HSA complexation process were evaluated to be (1.92 +/- 0.05)
      * 10(5)M(-1) and (1.04 +/- 0.05) * 10(5)M(-1), respectively. The binding was
      driven by a large negative standard molar enthalpic contribution. The binding was
      dominated essentially by non-polyelectrolytic forces which remained largely
      invariant at all salt concentrations. The polyelectrolytic contribution was weak
      at all salt concentrations and accounted for only 6-18% of the total standard
      molar Gibbs energy change in the salt concentration range 10-50mM. The negative
      standard molar heat capacity values, in conjunction with the enthalpy-entropy
      compensation phenomenon observed, established the involvement of dominant
      hydrophobic forces in the complexation process. Tartrazine enhanced the stability
      of both serum albumins against thermal denaturation.

PMID- 25577063
TI  - Brewing effect on levels of biogenic amines in different coffee samples as
      determined by LC-UV.
AB  - Eight biogenic amines (spermine, spermidine, putrescine, histamine, tyramine,
      phenylethylamine, cadaverine and serotonin) were determined by LC-UV after
      derivatization with dansyl-chloride in both ground coffee and coffee beverages
      obtained by different methods. In ground coffee, the most relevant amine was PUT,
      followed by SPD, HIS, TYR, CAD, SPM, PHE, and SER, with the total BAs content
      decreasing as the roasting degree increased. In coffee brews, the order was PUT,
      SPM, TYR, CAD, SPD, PHE, HIS, and SER, but at a very low level in comparison with
      the amount of BAs determined in roasted ground coffee. Beverages prepared by
      espresso, capsule, and pod machines had the lowest BAs contents, as a result of
      the thermal and physical stress imposed on ground coffee by these methods, while
      mocha contained the highest BAs amounts owing to lower pressure and longer
      brewing time. 

PMID- 25577064
TI  - Novel method for determination of zinc traces in beverages and water samples by
      solid surface fluorescence using a conventional quartz cuvette.
AB  - A new method for zinc pre-concentration/separation and determination by molecular
      fluorescence is proposed. The metal was complexed with o-phenanthroline and eosin
      at pH 7.5 in Tris; a piece of filter paper was used as a solid support and solid
      fluorescent emission measured using a conventional quartz cuvette. Under optimal
      conditions, the limits of detection and quantification were 0.36 * 10(-3) and
      1.29 * 10(-3) MUg L(-1), respectively, and the linear range from 1.29 * 10(-3) to
      4.50 MUg L(-1). This method showed good sensitivity and selectivity, and it was
      applied to the determination of zinc in foods and tap water. The absence of
      filtration reduced the consumption of water and electricity. Additionally, the
      use of common filter papers makes it a simpler and more rapid alternative to
      conventional methods, with sensitivity and accuracy similar to atomic
      spectroscopies using a typical laboratory instrument.

PMID- 25577065
TI  - Pre-mortem stress and the subsequent effect on flesh quality of pre-rigor
      filleted Atlantic salmon (Salmo salar L.) during ice storage.
AB  - The impact of pre-mortem stress and the subsequent effect on flesh quality of pre
      rigor filleted Atlantic salmon (Salmo salar L.) was investigated. Market-sized
      salmon were sampled before or during crowding, and before and after pumping and
      live chilling, representing accumulating stress and fatigue. Blood parameters
      (pH, Na(+), iCa, pCO2, pO2, glucose, Hct, lactate) and muscle pH confirm a
      stepwise increase of stress, depending on whether the fish were uncrowded
      (control), just crowded, uncrowded and chilled or crowded and chilled. Drip loss,
      water-holding capacity (WHC) and muscle pH during ice storage were not affected
      by pre-slaughtering conditions. However, a significant effect of storage time was
      observed. Significantly lowest firmness (N) was observed in crowded and chilled
      salmon whereas the cathepsin L activity was found to be significantly affected by
      crowding, live chilling and storage time. Moreover, small effects were observed
      regarding colour and contents of free amino acids. 

PMID- 25577066
TI  - Evaluation of dihydroquercetin-3-O-glucoside from Malbec grapes as copigment of
      malvidin-3-O-glucoside.
AB  - Malbec is a wine grape variety of great phenolic potential characterized for its
      high levels of anthocyanins and dihydroflavonols. To evaluate the possible
      implication of dihydroflavonols in the expression of red wine color through
      reactions of copigmentation or condensation, assays were carried out in wine
      model systems with different malvidin-3-O-glucoside:dihydroquercetin-3-O
      glucoside molar ratios. The addition of increasing levels of dihydroquercetin-3-O
      glucoside to a constant malvidin-3-O-glucoside concentration resulted in a
      hyperchromic effect associated with a darkening of the anthocyanin solutions,
      greater quantity of color and visual saturation, perceptible to the human eye.
      Copigmentation and thermodynamic measurements showed that dihydroquercetin-3-O
      glucoside can act as an anthocyanin copigment, similar to other usual wine
      components like flavanols or phenolic acids, although apparently less efficient
      than flavonols. The high levels of dihydroflavonols existing in Malbec wines in
      relation to other non-anthocyanin phenolics should make this family of compounds
      particularly important to explain the color expression in Malbec young red wines.

PMID- 25577067
TI  - Anthocyanins as markers for the classification of Argentinean wines according to
      botanical and geographical origin. Chemometric modeling of liquid chromatography
      mass spectrometry data.
AB  - A study of Argentinean red wines was performed by direct injection of untreated
      wine samples into a liquid chromatography-mass spectrometry system, processing
      the collected data with two chemometric algorithms: multivariate curve resolution
      with alternating least-squares and discriminant unfolded partial least-squares (D
      UPLS). The objectives were: (1) the chemometric resolution of profiles in the
      modes represented by elution time and m/z ratio, (2) the discrimination of
      samples according to varietal and/or geographical origin, and (3) the
      identification of key compounds helping to perform sample discrimination. The
      results indicate that all wine varietals can be adequately discriminated, and
      also three wine producing regions (located in the east, south and north of the
      Cuyo region) were differentiated from the remaining regions. The applied
      chemometric models allowed the tentative identification of anthocyanin compounds
      as responsible for both type of discriminations, in the case of D-UPLS by
      employing the concept of variables importance in the projection. 

PMID- 25577068
TI  - Optimization of a phase separation based magnetic-stirring salt-induced liquid
      liquid microextraction method for determination of fluoroquinolones in food.
AB  - Herein, we developed a novel integrated apparatus to perform phase separation
      based on magnetic-stirring, salt-induced, liquid-liquid microextraction for
      determination of five fluoroquinolones in animal-based foods by HPLC analysis.
      The novel integrated apparatus consisted of three simple HDPE (high density
      polyethylene) parts that were used to separate the solvent from the aqueous
      solution prior to retrieving the extractant. The extraction parameters were
      optimized using the response surface method based on central composite design:
      791 MUL of acetone solvent, 2.5 g of Na2SO4, pH 1.7, 3.0 min of stir time, and
      5.5 min centrifugation. The limits of detection were 0.07-0.53 MUg kg(-1) and
      recoveries were 91.6-105.0% for the five fluoroquinolones from milk, eggs and
      honey. This method is easily constructed from inexpensive materials, extraction
      efficiency is high, and the approach is compatible with HPLC analysis. Thus, it
      has excellent prospects for sample pre-treatment and analysis of fluoroquinolones
      in animal-based foods.

PMID- 25577069
TI  - A generic and rapid strategy for determining trace multiresidues of sulfonamides
      in aquatic products by using an improved QuEChERS method and liquid
      chromatography-electrospray quadrupole tandem mass spectrometry.
AB  - A rapid and efficient multiresidue method that involves using improved QuEChERS
      method and liquid chromatography-electrospray tandem mass spectrometry (LC-ESI
      MS/MS) was developed to measure trace levels of sulfonamides in fish tissue. This
      proposed method was proven to be a powerful, highly sensitive, and
      environmentally friendly analytical tool that requires minimal sample
      preparation. The typical MS/MS fragmentation patterns of the [M+H](+) were 156
      m/z, 108 m/z, and 92 m/z. Separation was performed on HC-C18 columns with a
      gradient elution by using methanol -5mM ammonium acetate containing formic acid
      (pH 3.5). This method was validated and exhibited favorable performance as well
      as acceptable accuracy (80.2-93.5%), precision (3.82-8.71%), sensitivity (limits
      of detection (LODs) 0.43-1.22 MUg kg(-1), limits of quantification (LOQs) 1.27
      3.71 MUg kg(-1); decision limit (CCalpha) 1.49-10.9 MUg kg(-1), detection
      capability (CCbeta) 1.71-11.4 MUg kg(-1)), and an acceptable matrix effect (-18.2
      18.4%). This methodology has been successfully applied in analyzing various fish
      tissue from local markets.

PMID- 25577070
TI  - Phosphoproteome analysis of sarcoplasmic and myofibrillar proteins in bovine
      longissimus muscle in response to postmortem electrical stimulation.
AB  - Protein phosphorylation changes of the sarcoplasmic and myofibrillar proteins in
      beef longissimus muscle in response to electrical stimulation (ES) was
      investigated. Sarcoplasmic and myofibrillar proteins purified from muscle samples
      taken at 0, 3 and 10h after ES were separated on SDS-PAGE and stained with
      phosphorous and protein specific stains. There was a significant effect of ES on
      phosphorylation of total sarcoplasmic and myofibrillar proteins (P<0.05).
      However, although there an instant effect of ES on the phosphorylation level of
      the myofibrillar proteins, the ES effect on the sarcoplasmic proteins (P<0.05)
      was first observed after 3h. Several protein bands were analyzed by LC-MS/MS,
      revealing that the major glycolytic proteins, including glycogen debranching
      enzyme, glycogen phosphorylase and 6-phosphofructokinase probably are affected by
      ES together with different heat shock proteins. This work gives an insight into
      the regulation of the glycolytic enzymes and muscle contraction on application of
      electrical stimulation. 

PMID- 25577071
TI  - Improvement of stability and carotenoids fraction of virgin olive oils by
      addition of microalgae Scenedesmus almeriensis extracts.
AB  - Humans are not capable of synthesizing carotenoids de novo and thus, their
      presence in human tissues is entirely of dietary origin. Consumption of essential
      carotenoids is reduced due to the lower intake of fruits and vegetables.
      Microalgae are a good source of carotenoids that can be exploited. In the present
      work, carotenoids rich extracts from Scenedesmus almeriensis were added to extra
      virgin olive oils at different concentrations (0.1 and 0.21 mg/mL) in order to
      enhance the consumption of these bioactives. Extracts brought changes in olive
      oils color, turning them orange-reddish. Quality of olive oils was improved,
      since peroxidation was inhibited. Olive oils fatty acids and tocopherols were not
      affected. beta-carotene and lutein contents increase considerably, as well as
      oxidative stability, improving olive oils shelf-life and nutritional value.
      Inclusion of S. almeriensis extracts is a good strategy to improve and enhance
      the consumption of carotenoids, since olive oil consumption is increasing.

PMID- 25577073
TI  - Effects of NaCl and soaking temperature on the phenolic compounds, alpha
      tocopherol, gamma-oryzanol and fatty acids of glutinous rice.
AB  - Soaking is one of the important steps of the parboiling process. In this study,
      we investigated the effect of changes in different sodium chloride (NaCl) content
      (0%, 1.5% and 3.0% NaCl, w/v) of soaking media and soaking temperatures (30
      degrees C, 45 degrees C and 60 degrees C) on the phenolic compounds (alpha
      tocopherol, gamma-oryzanol) and on the fatty acids of glutinous rice, compared
      with unsoaked samples. Overall, the total phenolic content, total phenolic acids,
      gamma-oryzanol, saturated fatty acid and mono-unsaturated fatty acid of the
      glutinous rice showed an increasing trend as NaCl content and soaking temperature
      increased, while alpha-tocopherol and polyunsaturated fatty acids decreased.
      Soaking at 3.0% NaCl provided the highest total phenolic content, total phenolic
      acids and gamma-oryzanol (0.2mg GAE/g, 63.61 MUg/g and 139.76 mg/100g,
      respectively) for the soaking treatments tested. Nevertheless, the amount of
      alpha-tocopherol and polyunsaturated fatty acid were found to be the highest
      (18.30/100g and 39.74%, respectively) in unsoaked rice.

PMID- 25577072
TI  - Microwave-assisted diluted acid digestion for trace elements analysis of edible
      soybean products.
AB  - A new method for the decomposition of soybean based edible products (soy extract,
      textured soy protein, transgenic soybeans, and whole soy flour) was developed to
      essential (Co, Cr, Cu, Fe, Mn, Ni, Se, V, and Zn) and non-essential (As, Ba, Cd,
      Pb, and Sr) trace elements determination by ICP OES and ICP-MS respectively.
      Effects related to the concentration of HNO3 (2.1-14.5 mol L(-1)) and the use of
      hydrogen peroxide on the efficiency of decomposition was evaluated based on the
      residual carbon content (RCC). It was demonstrated that 2.1 mol L(-1) HNO3 plus
      1.0 mL H2O2 was suitable for an efficient digestion, since RCC was lower than 18%
      and the agreement with certified values and spike recoveries were higher than 90%
      for all analytes. The concentrations of analytes in the samples (minimum-maximum
      in mgkg(-1)) were: The concentrations of analytes in the samples (minimum-maximum
      in mgkg(-1)) were: As (<0.007-0.040), Ba (0.064-10.6), Cd (<0.006-0.028), Co
      (0.012-102), Cr (0.56-5.88), Cu (6.53-13.9), Fe (24.9-126), Mn (16.4-35.2), Ni
      (0.74-4.78), Se (<2.90-25), Sr (2.48-20.1), Pb (<0.029-0.11), V (<0.027-20), and
      Zn (30.1-47.3). Soy-based foods investigated in this study presented variable
      composition in terms of essential and potentially toxic elements, which can be
      attributed to different methods of processing.

PMID- 25577074
TI  - Inactivation of tannins in milled sorghum grain through steeping in dilute NaOH
      solution.
AB  - Steeping milled sorghum in up to 0.4% NaOH was investigated as a method of tannin
      inactivation. NaOH steeping substantially reduced assayable total phenols and
      tannins in both Type III and Type II sorghums and with Type III sorghum caused a
      60-80% reduction in alpha-amylase inhibition compared to a 20% reduction by water
      steeping. NaOH treatment also reduced starch liquefaction time and increased free
      amino nitrogen. Type II tannin sorghum did not inhibit alpha-amylase and
      consequently the NaOH treatment had no effect. HPLC and LC-MS of the tannin
      extracts indicated a general trend of increasing proanthocyanidin/procyanidin
      size with increasing NaOH concentration and steeping time, coupled with a
      reduction in total area of peaks resolved. These show that the NaOH treatment
      forms highly polymerised tannin compounds, too large to assay and to interact
      with the alpha-amylase. NaOH pre-treatment of Type III sorghums could enable
      their utilisation in bioethanol production. 

PMID- 25577075
TI  - A direct correlation between the antioxidant efficiencies of caffeic acid and its
      alkyl esters and their concentrations in the interfacial region of olive oil
      emulsions. The pseudophase model interpretation of the "cut-off" effect.
AB  - Recently published results for a series of homologous antioxidants, AOs, of
      increasing alkyl chain length show a maximum in AO efficiency followed by a
      significant decrease for the more hydrophobic AOs, typically called the "cut-off"
      effect. Here we demonstrate that in olive oil emulsions both antioxidant
      efficiencies and partition constants for distributions of AOs between the oil and
      interfacial regions, PO(I), show a maximum at the C8 ester. A reaction between
      caffeic acid, CA, and its specially synthesised C1-C16 alkyl esters, and a
      chemical probe is used to estimate partition constants for AO distributions and
      interfacial rate constants, kI, in intact emulsions based on the pseudophase
      kinetic model. The model provides a natural interpretation for both the maximum
      and the "cut-off" effect. More than 70% of the CA esters are in the interfacial
      region even at low surfactant volume fraction, PhiI=0.005.

PMID- 25577076
TI  - Concentration of some heavy metals in rice types available in Shiraz market and
      human health risk assessment.
AB  - This investigation was conducted to survey the levels of some heavy metals such
      as cadmium, lead, chromium, nickel and cobalt in domestic cultivated and imported
      rice sold on the Shiraz - Iran markets. The potential human health risk
      assessment was conducted by considering estimated weekly intake (EWI) of toxic
      metals from eating rice and compared calculated values with provisional tolerable
      weekly intake (PTWI). The mean values for lead and cadmium in domestic cultivated
      and imported rice were considerably higher than allowable limits set by FAO/WHO.
      In combination of recent rice consumption data, the estimated weekly intakes of
      toxic element were calculated for Iranian population. EWI for cadmium, nickel,
      chromium through imported and domestic cultivated rice consumption was lower than
      the PTWI. The EWI for lead were considerably higher than other measured toxic
      metals. The highest mean level of EWI for lead was observed in some imported rice
      samples (25.76 MUg/kg body weight).

PMID- 25577077
TI  - Influence of protein type on oxidation and digestibility of fish oil-in-water
      emulsions: gliadin, caseinate, and whey protein.
AB  - The influence of three surface-active proteins on the oxidative stability and
      lipase digestibility of emulsified omega-3 oils was examined: deamidated wheat
      gliadin (gliadin); sodium caseinate (CN); whey protein isolate (WPI). Gliadin and
      WPI were more effective at inhibiting lipid oxidation (hydroperoxides and TBARS)
      of fish oil-in-water emulsions than CN. Protein oxidation during storage was
      determined by measuring the loss of tryptophan fluorescence. The CN-emulsions
      exhibited the highest loss of tryptophan fluorescence during aging, as well as
      the highest amount of lipid oxidation. Potential reasons for the differences in
      oxidative stability of the emulsions with different proteins include differences
      in interfacial film thickness, protein chelating ability, and antioxidant amino
      acids profiles. During in vitro digestion, gliadin-stabilized emulsions had the
      lowest digestion rate of the three proteins. These results have important
      implications for using proteins to fabricate emulsion-based delivery systems for
      omega-3 oils. 

PMID- 25577078
TI  - Purification and identification of novel antioxidant peptides from egg white
      protein and their antioxidant activities.
AB  - The aim of this study was to isolate antioxidant peptides from egg white protein
      hydrolysates (EWPH) and identify novel antioxidant peptides by LC tandem mass
      spectrometric and mid-infrared spectroscopy (MIR). The amino acid composition of
      peptides was also analyzed by amino acid analyzer on the basis of ninhydrin
      reaction. Three novel peptides with molecular weights of 628.64 Da, 630.71 Da,
      and 684.1 Da were identified as Asp-His-Thr-Lys-Glu (DHTKE), Phe-Phe-Glu-Phe-His
      (FFGFN) and Met-Pro-Asp-Ala-His-Leu (MPDAHL), respectively. DHTKE exhibited the
      best oxygen radical absorbance capacity (P<0.05). The concentration of FFGFN and
      MPDAHL to scavenge 50% of DPPH radicals was 80 mM and 60mM, respectively. Thus,
      the three peptides may have potential applications as a functional food, which
      could also be used as nutraceutical compounds.

PMID- 25577079
TI  - Phospholipids and terpenes modulate Caco-2 transport of acai anthocyanins.
AB  - Anthocyanins (ANC) are common polyphenolics in plants, but are poorly absorbed
      into the bloodstream upon consumption. Phospholipids (PL) and terpenes (TP) may
      serve as enhancing agents in absorption. This study evaluated their role in
      transepithelial transport within a Caco-2 cell monolayer-model system and impact
      on ANC stability. Acai fruit ANC were isolated and found to transport, at a low
      rate (1.22%), in the absence of soy lecithin phospholipids and Valencia orange
      terpenes, yet their addition significantly increased the transport of both
      cyanidin-3-glucoside and cyanidin-3-rutinoside. The best transport results
      (5.21%) were observed when combinations of PL (5000 mg/l) and TP (50mg/l) were
      used. The presence of PL and TP had no influence on ANC degradation over a 40 day
      storage period. Results demonstrated the potential of PL and TP to increase
      intestinal transport of ANC, and present advancement towards the formulation of
      functional foods that support improved ANC absorption.

PMID- 25577080
TI  - HPLC and LC-MS/MS methods for determination of sodium benzoate and potassium
      sorbate in food and beverages: performances of local accredited laboratories via
      proficiency tests in Turkey.
AB  - High Performance Liquid Chromatography LC-UV and LC-MS/MS methods were developed
      and validated for quantitative analyses of sodium benzoate and potassium sorbate
      in foods and beverages. HPLC-UV and LC-MS/MS methods were compared for
      quantitative analyses of sodium benzoate and potassium sorbate in a
      representative ketchup sample. Optimisation of the methods enabled the
      chromatographic separation of the analytes in less than 4 min. A correlation
      coefficient of 0.999 was achieved over the measured calibration range for both
      compounds and methods (HPLC and LC-MS/MS). The uncertainty values of sodium
      benzoate and potassium sorbate were found as 0.199 and 0.150 mg/L by HPLC and
      0.072 and 0.044 mg/L by LC-MS/MS, respectively. Proficiency testing performance
      of Turkish accredited laboratories between the years 2005 and 2013 was evaluated
      and reported herein. The aim of the proficiency testing scheme was to evaluate
      the performance of the laboratories, analysing benzoate and sorbate in tomato
      ketchup.

PMID- 25577081
TI  - Bioactive beta-carbolines norharman and harman in traditional and novel raw
      materials for chicory coffee.
AB  - The beta-carboline compounds norharman and harman exhibit neuroactive activity in
      the human body. Chicory coffee has proved to be a source of beta-carboline
      compounds. This study assessed the norharman and harman contents of traditional
      and novel raw materials for the production of chicory coffee, as well as in
      samples of chicory coffee with novel additives. The highest content of the beta
      carbolines among the traditional raw materials was recorded in roasted sugar beet
      (2.26 MUg/g), while roasting the chicory caused a 25-fold increase in the content
      of norharman in this raw material (from 0.05 to 1.25 MUg/g). In novel raw
      materials not subjected to the action of high temperature, beta-carboline was not
      detected. Among the roasted novel raw materials, the highest contents of harman
      and norharman were found in artichokes. High harman levels were also recorded in
      roasted chokeberry.

PMID- 25577082
TI  - Fluorescence spectroscopy coupled with PARAFAC and PLS DA for characterization
      and classification of honey.
AB  - Fluorescence spectroscopy coupled with parallel factor analysis (PARAFAC) and
      Partial least squares Discriminant Analysis (PLS DA) were used for
      characterization and classification of honey. Excitation emission spectra were
      obtained for 95 honey samples of different botanical origin (acacia, sunflower,
      linden, meadow, and fake honey) by recording emission from 270 to 640 nm with
      excitation in the range of 240-500 nm. The number of fluorophores present in
      honey, excitation and emission spectra of each fluorophore, and their relative
      concentration are determined using a six-component PARAFAC model. Emissions from
      phenolic compounds and Maillard reaction products exhibited the largest
      difference among classes of honey of different botanical origin. The PLS DA
      classification model, constructed from PARAFAC model scores, detected fake honey
      samples with 100% sensitivity and specificity. Honey samples were also classified
      using PLS DA with errors of 0.5% for linden, 10% for acacia, and about 20% for
      both sunflower and meadow mix.

PMID- 25577083
TI  - Functionality study of Na6PMo11FeO40 as a mushroom tyrosinase inhibitor.
AB  - The inhibitory effects of iron-substituted phosphomolybdic acid (Na6PMo11FeO40,
      abbreviated as PMo11Fe) on mushroom tyrosinase were investigated. The Native-PAGE
      results show that PMo11Fe has an inhibitory effect on tyrosinase. A
      spectrophotometric analysis shows that PMo11Fe is a reversible and noncompetitive
      inhibitor with KI=KIS=0.47 mmol L(-1). The effects of PMo11Fe on the preservation
      of lotus root slices were studied. The results show that PMo11Fe can
      significantly slow the browning rate of lotus root slices, inhibit the activity
      of polyphenol oxidase (PPO), enhance the activity of peroxidase (POD) and
      superoxide dismutase (SOD), maintain high levels of glutathione (GSH), ascorbic
      acid (ASA) and sucrose and control the peroxidation degree of fresh-cut fruits
      and vegetables. This study may help to elucidate the design of mushroom
      tyrosinase inhibitors of polyoxometalates (abbreviated as POMs) and a theoretical
      basis for the use of POMs to inhibit fruit spoilage.

PMID- 25577084
TI  - LC-MS investigations on interactions between isolated beta-lactoglobulin peptides
      and lipid oxidation product malondialdehyde.
AB  - Interactions between secondary lipid oxidation product malondialdehyde (MDA) and
      selected beta-lactoglobulin (beta-Lg) peptides were investigated. Selected
      tryptic peptides of beta-Lg (ALPMHIR, LIVTQTMK and VLVLDTDYK) were fractionated
      via preparative-HPLC and incubated with MDA at 37 degrees C and 60 degrees C for
      7 days. Changes in samples were monitored with LC-ESI-MS coupled with UV and
      fluorescence detectors. Prominent modifications in peptide samples included
      formation of two distinct types of MDA adducts observed with mass increments of
      54 and 134 amu, corresponding to Schiff base and dihydropyridine (DHP)-type
      adducts, respectively. Modified peptides with m/z +54 amu were more stable at 37
      degrees C than at 60 degrees C but showed more rapid formation than compounds
      with m/z +134 amu. MDA-peptide adducts resulting in +134 amu mass increment
      displayed strong fluorescent characteristics and they were more stable than
      Schiff base adducts at 60 degrees C.

PMID- 25577085
TI  - Water-soluble extracts from defatted sesame seed flour show antioxidant activity
      in vitro.
AB  - Defatted white and gold sesame seed flour, recovered as a byproduct after sesame
      oil extraction, was extracted with 70% ethanol to obtain polar-soluble crude
      extracts. The in vitro antioxidant activity of the extract was evaluated by DPPH
      free radical scavenging activity and oxygen radical absorbing capacity (ORAC).
      The polar-soluble crude extracts of both sesame seed types exhibited good
      antioxidant capacity, especially by the ORAC method with 34,720 and 21,700 MUmol
      Trolox equivalent/100g of white and gold sesame seed extract, respectively. HPLC,
      butanol extraction, and UPLC-MS analyses showed that different compounds
      contributed to the antioxidant activity of the polar-soluble crude extracts.
      Sesaminol glycosides were identified in the butanol-soluble fractions; whereas,
      purified water-soluble fraction contained ferulic and vanillic acids. This study
      shows that hydrophilic antioxidants in the purified water-soluble fraction
      contributed to the antioxidant activity of white and gold sesame seed polar
      soluble crude extracts.

PMID- 25577086
TI  - Development of a colorimetric sensor array for squid spoilage assessment.
AB  - The aim of this work was to develop and evaluate a rapid, easy-to-use
      optoelectronic system for the shelf-life assessment of squid in cold storage. For
      this purpose, an optoelectronic nose was designed, which consisted of an array
      containing six sensing materials prepared by combining different dyes and two
      inorganic supports (aluminium oxide and silica gel). Samples were packaged with
      the colorimetric array and kept in cold storage for 12 days. Squid spoilage was
      monitored simultaneously by the colorimetric array and by the physico-chemical
      and microbial analyses during storage. Samples exceeded the acceptability limits
      for microbial counts on the third day. PCA analysis carried out with CIELab
      showed that the colorimetric array was able to discriminate between fresh squid
      fit for consumption and spoiled squid. The statistical models obtained by PLS,
      with the optoelectronic nose, successfully predicted CO2 and O2 content in the
      headspace as well as microbial growth.

PMID- 25577087
TI  - Effect of preprocessing and compressed propane extraction on quality of cilantro
      (Coriandrum sativum L.).
AB  - Dehydration leads to quality defects in cilantro such as loss in structure,
      color, aroma and flavor. Solvent extraction with compressed propane may improve
      the dehydrated quality. In the present study, effect of drying temperature,
      particle size, and propane extraction on color, volatile composition, and fatty
      acid composition of cilantro was evaluated. Cilantro was dehydrated (40 degrees C
      or 60 degrees C), size reduced and separated into three particles sizes, and
      extracted with compressed propane at 21-27 degrees C. Major volatile compounds
      found in dried cilantro were E-2-tetradecenal, dodecanal, E-2-dodecenal, and
      tetradecanal. Major fatty acids were linoleic acid and alpha-linolenic acid.
      Drying at 60 degrees C compared to 40 degrees C resulted in better preservation
      of color (decrease in browning index values) and volatile compounds. Propane
      extraction led to a positive change in color values and a decrease in volatile
      composition, oil content, and fatty acid composition. 

PMID- 25577088
TI  - Influence of deficit irrigation timing on the fruit quality of grapefruit (Citrus
      paradisi Mac.).
AB  - The irrigation necessities for grapefruit production are very high. Due to the
      scarcity of water resources, growers use deficit irrigation (DI) - which could
      affect the fruit quality. Different DI strategies were studied: Control
      (irrigated at 100% ETc) and T1, T2 and T3 (50% ETc at phases I, II and III of
      fruit growth, respectively). Strategy T1 only delayed external maturation
      depending on the duration of the water stress. High water stress in T2 delayed
      fruit maturation, increased acidity and reduced the sugar concentration. Under
      T2, trees suffering moderate water stress showed increased flavonoid and phenolic
      contents but decreased lycopene levels. External maturation was delayed in T3
      when severe stress occurred during the first part of phase III. Strategy T3
      advanced internal ripening when moderate water stress occurred during the first
      40 days of phase III, increasing sugar accumulation, promoted by the high acidity
      of the fruits. Moderate water stress also increased beta-carotene, flavonoids and
      phenolics levels.

PMID- 25577089
TI  - In silico methods to identify meat-derived prolyl endopeptidase inhibitors.
AB  - According to the World Health Organization (WHO), approximately 450 million
      people suffer from mental or neurological disorders and five of the ten leading
      causes of disability and premature death worldwide are psychiatric conditions.
      Social, biological and neurological sciences provided extensive understanding
      into the role of risk and protective factors in the development of mental
      disorders and poor mental health. Altered activity of a number of enzymes, such
      as prolyl endopeptidase (PEP, EC 3.4.21.26), has been linked to the prevention
      and treatment of a number of mental disorders, including anxiety, depression and
      Alzheimer's disease. The inhibition of PEP has potential for use in the
      prevention and in the treatment of mental disorders. The objective of this work
      was to identify PEP-inhibitory peptides from meat proteins using in silico
      methods. In this paper, five proteins commonly found in meat by-products were
      evaluated as a substrate for use in the generation of PEP inhibitory peptides.
      These include serum albumin, collagen and myosin. These proteins were cleaved in
      silico using BIOPEP and ExPASy PeptideCutter and the generated peptides were
      compared to known PEP-inhibiting peptides in the database of BIOPEP. A number of
      novel PEP inhibitory peptide sequences were identified in this study, including
      PPL, APPH, IPP and PPG with corresponding IC50 values of 2.86, 3.95, 4.02 and
      2.70 mM, respectively. This work demonstrates the usefulness of in silico
      analysis for predicting the release of PEP-inhibiting peptides from meat
      proteins.

PMID- 25577090
TI  - Microcapsule preparation of allyl isothiocyanate and its application on mature
      green tomato preservation.
AB  - Studies have shown that AITC can effectively control pathogenic fungi, which
      cause fruits and vegetables decay and rotting during storage. However, because of
      its strong irritant, AITC has not been conveniently used in fruits and vegetables
      preservation. Microencapsulation techniques may solve this problem. Up to 2%
      (w/v) gelatin and 2% (w/v) gum arabic (as wall material and materials), as well
      as AITC (as core material) were prepared used to form microcapsules with a ratio
      of 1:2 (the core material: to wall material). On the basis of the microcapsule
      option conditions, the AITC microcapsule encapsulation efficiency is above 90%,
      which can effectively control AITC release decrease irritant. Compared with
      control group, the storage time of the tomato of AITC microcapsule preservation
      was prolonged significantly, and the sensory quality of the tomato was better.
      Thus, the AITC microcapsule preservation has broad application prospects and
      development value prospects. 

PMID- 25577091
TI  - Supplemental selenium improves wheat grain yield and quality through alterations
      in biochemical processes under normal and water deficit conditions.
AB  - The paper mainly reported the effects of exogenous selenium (Se) supply (Se seed
      priming, Se fertigation and Se foliar spray) on physiological and antioxidant
      system of wheat aiming to clarify its effect on yield and nutritional quality of
      wheat under both normal and water deficit conditions. Water stress markedly
      decreased the grain Se, iron (Fe), phosphorous (P), zinc (Zn) and magnesium (Mg)
      contents. Supplemental Se (Na2SeO4) improved the yield and quality of water
      stressed plants due to enhancement in the production of osmoprotectants and
      increased activity of antioxidant enzymes. The foliar spray of Se was more
      effective than Se fertigation and Se seed treatment. To the best of our
      knowledge, this is the first elaborate study that involved various Se application
      methods to evaluate the efficiency of Se supply to plants that would be crucial
      to develop better understanding of Se translocation and accumulation within crop
      plants under drought stress. 

PMID- 25577092
TI  - Isolation of antioxidant phytoconstituents from the seeds of Lens culinaris
      Medik.
AB  - Lens culinaris Medik (Leguminosae) is an annual, bushy and herbaceous plant
      cultivated globally for its edible seeds. A methanolic extract of the seeds
      contained four new antioxidant compounds, namely beta-sitosteryl-3-(2'-n
      eicosanyloxy)-benzoate (3), n-octadec-9-enoyl-1-beta-D-glucurano-pyranoside (4)
      alpha-D-galactopyranosyl-(6 -> 1')-alpha-D-galactopyranosyl-(6' -> 1")-alpha-D
      galactopyranosyl-(6" -> 1''')-alpha-d-galactopyranoside (5) and benzoyl-O-alpha-D
      glucopyranosyl-(2a -> 1b)-O-alpha-D-glucopyranosyl-(2b -> 1c)-O-alpha-D
      glucopyranosyl-(6c -> 1d)-O-alpha-D-glucopyranosyl-(6d -> 1e)-O-alpha-D-gluco
      pyranoside (6) along with two known compounds n-heptadecanyl n-octadec-9-enoate
      (1) and beta-sitosterol (2) on the basis of chromatographic and spectral data
      analytical techniques. Compound 3 showed significant antioxidant activity
      compared to compounds 4, 5, and 6.

PMID- 25577093
TI  - A validated HPLC method for the analysis of herbal teas from three chemotypes of
      Brazilian Lippia alba.
AB  - Infusions and decoctions of three chemotypes of Lippia alba (Mill.) N. E. Brown
      (Verbenaceae) were investigated for their quantitative profiles by HPLC-DAD-ESI
      MS analyses. An RP-HPLC method was developed which permitted the quality control
      of the preparations. The correct choice of the column allowed the detailed
      characterization of the constituents in a total analysis time of 35 min. The HPLC
      method was accordingly validated for linearity range, LOD, LOQ, accuracy and
      precision. For the quantitative analysis the three major phytochemical groups
      were taken into consideration, namely iridoids, phenylpropanoids and flavonoids.
      Comparative quantitative analyses revealed significant differences among the
      chemotypes that should be taken into account in the uses of the herbal teas. The
      developed HPLC-UV assay proved to be an efficient and alternative method for the
      discrimination of the three chemotypes. This is the first report of detailed
      analysis of the chemical composition of the constituents of L. alba chemotypes'
      teas.

PMID- 25577094
TI  - Effect of malondialdehyde treatment on the IgE binding capacity and
      conformational structure of shrimp tropomyosin.
AB  - The aim of this work was to determine the effect of malondialdehyde (MDA)
      treatment of shrimp tropomyosin (TM) with respect to IgE binding capacity and
      conformational structure. Following treatment with MDA, changes in TM molecular
      weight were characterized by SDS-PAGE and TM cross-linking was observed, then the
      aggregates were recognized by IgG/IgE in immunoblot analysis. Meanwhile, TM
      allergenicity slowly decreased following MDA treatment. These data show a
      correlation between the loss of TM structure and allergenic potential. TM
      secondary structure became more disordered following treatment with increasing
      concentrations of MDA. Moreover, the enhancement of surface hydrophobicity was
      also in accordance with the effect caused by MDA. Additionally, MDA treatment
      resulted in an increase in carbonyl content and a decrease in free amine groups
      and available lysine. The results suggest that MDA-induced conformational changes
      in TM can significantly influence the antigenicity and allergenicity of TM. 

PMID- 25577095
TI  - Proteomic identification of allergenic seed proteins, napin and cruciferin, from
      cold-pressed rapeseed oils.
AB  - In Finland and France atopic children commonly react to seeds of oilseed rape and
      turnip rape in skin prick tests (SPT) and open food challenges. These seeds are
      not as such in dietary use and therefore the routes of sensitization are unknown.
      Possible allergens were extracted from commercial cold-pressed and refined
      rapeseed oils and identified by gel-based tandem nanoflow liquid chromatography
      mass spectrometry (LC-MS/MS). Napin (a 2S albumin), earlier identified as a major
      allergen in the seeds of oilseed rape and turnip rape, and cruciferin (an 11S
      globulin), a new potential seed allergen, were detected in cold-pressed oils, but
      not in refined oils. Pooled sera from five children sensitized or allergic to
      oilseed rape and turnip rape seeds reacted to these proteins from cold-pressed
      oil preparations and individual sera from five children reacted to these proteins
      extracted from the seeds when examined with IgE immunoblotting. Hence cold
      pressed rapeseed oil might be one possible route of sensitization for these
      allergens. 

PMID- 25577096
TI  - Trypsin from the digestive system of carp Cirrhinus mrigala: purification,
      characterization and its potential application.
AB  - Trypsin was purified 35.64-fold with 4.97% recovery from the viscera of carp
      Cirrhinus mrigala (mrigal) by ammonium sulfate precipitation, ion exchange and
      affinity chromatography. The purified enzyme was active at a wide range of pH
      (7.0-9.2) and temperature (10-50 degrees C). The purified enzyme exhibited high
      thermal stability up to 50 degrees C for 1h. The enzyme activity was stabilized
      by Ca(+2) (2mM) up to 7h at 40 degrees C. The Km and kcat values of purified
      enzyme were 0.0672 mM and 92.09/s/mM, respectively. Soybean trypsin inhibitor and
      phenylmethylsulphonylflouride completely inhibited the enzyme activity. The
      specific inhibitor of trypsin, N-alpha-p-tosyl-L-lysine chloromethyl ketone
      inhibited 99.67% activity. Na(+), K(+) and Li(+) inhibited 20.99 +/- 5.25%, 16.53
      +/- 4.80% and 18.99 +/- 1.42% of enzyme activity, respectively. Divalent ions
      Mg(+2), Zn(+2), Co(+2), Hg(+2) and Cd(+2) inhibited 21.61 +/- 2.22%, 31.62 +/-
      1.78%, 31.62 +/- 1.96%, 85.68 +/- 1.51% and 47.95 +/- 2.13% enzyme activity,
      respectively. SDS-PAGE showed that the molecular mass of purified enzyme was 21.7
      kDa. MALDI-TOF study showed a peptide sequence of AFCGGSLVNENKMHSAGHCYKSRIQV at
      the N-Terminal. This sequence recorded 76-84% identity with trypsin from Thunnus
      thynnus and other fish species. This confirmed that the purified protein was
      trypsin. The purified enzyme has potential applications in detergent and food
      industry because of its thermal stability and alkaline nature.

PMID- 25577097
TI  - Determination of ametoctradin residue in fruits and vegetables by modified quick,
      easy, cheap, effective, rugged, and safe method using ultra-performance liquid
      chromatography/tandem mass spectrometry.
AB  - A rapid, effective and sensitive method to quantitatively determine ametoctradin
      residue in apple, cucumber, cabbage, tomato and grape was developed and validated
      using ultra-performance liquid chromatography coupled with tandem mass
      spectrometry (UPLC-MS/MS). The target compound was determined in less than 5.0
      min using an electrospray ionisation source in positive mode (ESI+). The limit of
      detection was below 0.043 MUg kg(-1), whereas the limits of quantification did
      not exceed 0.135 MUg kg(-1) in all five matrices. The method showed excellent
      linearity (R(2)>0.9969) for the target compound. Recovery studies were performed
      in all matrices at three spiked levels (1, 10 and 100 MUg L(-1)). The mean
      recoveries from five matrices ranged from 81.81% to 100.1%, with intra-day
      relative standard deviations (RSDr) in the range of 0.65-7.88% for the test
      compound. This method will be useful for the quick and routine detection of
      ametoctradin residues in potato, grape, cucumber, apple and tomato.

PMID- 25577098
TI  - Analysis of volatile thiols in alcoholic beverages by simultaneous
      derivatization/extraction and liquid chromatography-high resolution mass
      spectrometry.
AB  - A simultaneous derivatization/extraction method followed by liquid chromatography
      electrospray-high resolution mass spectrometry for the determination of volatile
      thiols in hydroalcoholic matrixes was optimized and used to identify and quantify
      volatile thiols in wine and beer samples. The method was evaluated in terms of
      sensitivity, precision, accuracy and selectivity. The experimental LOQs of eleven
      thiols tested ranged between 0.01 ng/L and 10 ng/L. Intra-day relative standard
      deviation (RSD) was in general lower than 10% and inter-day RSD ranged between
      10% and 30%. Recovery in the model and real matrixes ranged from 45% to 129%. The
      method was then applied for the analysis of four white wines and six beers. Five
      out of the eleven reference thiols were identified and quantified in the samples
      analyzed. The non-target approach, carried out by monitoring the diagnostic ion
      at m/z 275.9922 [C13H10ONSe](+) in the fragmentation spectrum, allowed detecting,
      in the same samples, fourteen non-target thiols.

PMID- 25577099
TI  - Screening antimutagenic and antiproliferative properties of extracts isolated
      from Jackfruit pulp (Artocarpus heterophyllus Lam).
AB  - The present focused on the study of the antimutagenic and antiproliferative
      potential of pulp Jackfruit (Artocarpus heterophyllus Lam) extract, using
      Salmonella typhimurium tester strains TA98 and TA100 with metabolic activation
      (S9) and a cancer cell line M12.C3.F6 (murine B-cell lymphoma), respectively.
      Jackfruit pulp extract was sequentially fractionated by chromatography (RP-HPLC)
      and each fraction was tested for antimutagenic and antiproliferative activities.
      The organic extracts obtained from Jackfruit pulp reduced the number of
      revertants caused by aflatoxin B1 (AFB1) and proliferation of cells M12.C3.F6; a
      dose-response relationship was showed. Sequential RP-HPLC fractionation of the
      active extracts produced both antimutagenic and/or antiproliferative fractions.
      These results suggested that the Jackfruit contained compounds with
      chemoprotective properties to reduce the mutagenicity of AFB1, also proliferation
      of a cancer cell line. 

PMID- 25577100
TI  - Potential of hyperspectral imaging for rapid prediction of hydroxyproline content
      in chicken meat.
AB  - In this study, the potential of hyperspectral imaging (HSI) for predicting
      hydroxyproline content in chicken meat was investigated. Spectral data contained
      in the hyperspectral images (400-1000 nm) of chicken meat was extracted, and a
      partial least square regression (PLSR) model was then developed for predicting
      hydroxyproline content. The model yielded acceptable results with regression
      coefficient in prediction (Rp) of 0.874 and root mean error squares in prediction
      (RMESP) of 0.046. Based on the eight optimal wavelengths selected by regression
      coefficients (RC) from the PLSR model, a new RC-PLSR model was built and good
      results were shown with high Rp of 0.854 and low RMSEP of 0.049. Finally,
      distribution maps of hydroxyproline were created by transferring the RC-PLSR
      model to each pixel in the hyperspectral images. The results demonstrated that
      HSI has the capability for rapid and non-destructive determination of
      hydroxyproline content in chicken meat.

PMID- 25577101
TI  - Fatty acid composition of Swedish bakery products, with emphasis on trans-fatty
      acids.
AB  - Trans-fatty acids (TFA) have been associated with increased risk of coronary
      heart disease, by affecting blood lipids and inflammation factors. Current
      nutrition recommendations emphasise a limitation of dietary TFA intake. The aim
      of this study was to investigate fatty acid composition in sweet bakery products,
      with emphasis on TFA, on the Swedish market and compare fatty acid composition
      over time. Products were sampled in 2001, 2006 and 2007 and analysed for fatty
      acid composition by using GC. Mean TFA levels were 0.7% in 2007 and 5.9% in 2001
      of total fatty acids. In 1995-97, mean TFA level was 14.3%. In 2007, 3 of 41
      products had TFA levels above 2% of total fatty acids. TFA content had decreased
      in this product category, while the proportion of saturated (SFA) and
      polyunsaturated (PUFA) fatty acids had increased, mostly through increased levels
      of 16:0 and 18:2 n-6, respectively. The total fat content remained largely
      unchanged. 

PMID- 25577102
TI  - Expression and characterization of a novel beta-glucosidase, with
      transglycosylation and exo-beta-1,3-glucanase activities, from Rhizomucor miehei.
AB  - A novel beta-glucosidase gene, designated RmBglu3B, was cloned from the
      thermophilic fungus, Rhizomucor miehei CAU432. Its 2196-bp open reading frame
      encoded 731 amino acids. Its deduced amino-acid sequence showed highest identity
      (66%) with a glycoside hydrolase family 3 beta-glucosidase from R. miehei
      NRRL5382. RmBglu3B was successfully expressed in Escherichia coli. The
      recombinant enzyme was purified to homogeneity with 18.2-fold purification and
      59% recovery yield. Molecular masses of 76.5 kDa, by SDS-PAGE, and 66.4 kDa, by
      gel filtration, suggested that it is a monomer. Optimal pH and temperature of the
      purified enzyme were 5.0 and 50 degrees C, respectively. RmBglu3B exhibited a
      broad range of substrate specificity, catalyzing the cleavage of beta-1,2, beta
      1,3, beta-1,4 and beta-1,6 linkages, in various oligosaccharides, to liberate
      glucose. RmBglu3B also showed relatively high activity (19.1 U/mg) toward
      laminaran and transglycosylation activity, enabling gentiobiose production. This
      enzyme is a potential candidate for several industrial applications.

PMID- 25577103
TI  - Furan formation from fatty acids as a result of storage, gamma irradiation, UV-C
      and heat treatments.
AB  - The effects of gamma and UV-C irradiation in comparison with thermal processing
      and storage at 25 degrees C on formation of furan from different fatty acids were
      investigated. Results showed that furan was generated from polyunsaturated fatty
      acids such as linoleic and linolenic acid during thermal (120 degrees C, 25 min)
      and UV-C (11.5 J/cm(2)) treatments. Gamma irradiation (up to 20 kGy) did not
      induce formation of significant amounts of furan from any of the fatty acids
      studied. Storage of unsaturated fatty acid emulsions at 25 degrees C for 3 days
      led to the formation of furan (7-11 ng/mL) even without prior thermal or non
      thermal treatments. pH significantly impacted furan formation with >3.5 times
      more furan formed at pH 9 than at pHs 3 or 6 during 3 days at 25 degrees C. The
      addition of Trolox, BHA, and propyl gallate had no significant effect on furan
      formation from linolenic acid while alpha-tocopherol and FeSO4 promoted furan
      formation.

PMID- 25577104
TI  - Organically vs conventionally grown winter wheat: effects on grain yield,
      technological quality, and on phenolic composition and antioxidant properties of
      bran and refined flour.
AB  - Since organic food is widely assumed to have a better nutritional quality than
      conventional food, our aim was to study the effects of organic vs conventional
      cropping systems on yield and the phenolic composition of winter wheat cv.
      'Bologna'. Although organic wheat yielded less than conventional wheat, mainly
      due to the nitrogen shortage, and its bread-making quality was lower, the
      cultivation system did not affect the total amounts of phenolics and phenolic
      acids. Of the eight phenolic acids identified, only ferulic acid was influenced
      by the cultivation system. Phenolic composition and quantity were significantly
      affected by the milling fraction (bran or white flour): phenolics were more
      concentrated in the bran, which showed the highest antioxidant power. Under the
      conditions adopted in this study, an organic cropping system can maintain or even
      increase the health properties of the wheat milled products, provided a reduction
      in grain yield is accepted. 

PMID- 25577105
TI  - Determination of EDTA in feed and premix formulations by HPLC-DAD.
AB  - A simple analytical method for the quantitative determination of
      ethylenediaminetetraacetic acid (EDTA) in feed and premix formulations was
      developed and validated. The method involves an extraction with an acidic ferric
      chloride solution, to quantitatively convert EDTA species in the samples into the
      Fe(III)-EDTA complex, and its subsequent detection by Ion-Pair-Reversed Phase
      High Performance Liquid Chromatography-Diode Array Detection (IP-RP-HPLC-DAD). A
      robust validation procedure was performed according to the Decision 2002/657/EC
      at concentrations ranging from 25 to 100 mg kg(-1) on sample. Good recoveries
      (85.6-92.8%) were obtained; repeatability of the method was in the range of 1.3
      8.0%, with an intermediate precision ranging from 6.0% to 8.6%, both of them
      expressed as relative standard deviation (RSD). No interfering species hindered
      the straightforward detection of EDTA. Hence, the proposed method can be adopted
      for an effective and rapid routine analysis of products for livestock.

PMID- 25577106
TI  - Effect of simulated processing on the antioxidant capacity and in vitro protein
      digestion of fruit juice-milk beverage model systems.
AB  - The effects of simulated processing (pH adjustment and thermal treatment) on the
      antioxidant capacity and in vitro protein digestion of fruit juice-milk beverage
      (FJMB) models consisting of whey protein (WP), and chlorogenic acid (CHA) or
      catechin (CAT) were investigated. Results indicated that CAT was more susceptible
      to processing than CHA, and showed a significant (p < 0.05) decrease in ABTS and
      FRAP after sterilization (121 degrees C/10 min) and pH adjustment to 6.8. WP
      addition had different effects (none, masking, synergetic effect) on the
      antioxidant activity of FJMB. Pasteurization (63 degrees C/30 min) and pH
      adjustment (pH 3.7 or pH 6.8) had either non-significant or slight effects on
      FJMB's antioxidant capacity, while sterilization significantly (p<0.05) increased
      or decreased its ABTS and FRAP depending on the different models. In vitro
      digestion of WP in FJMB was obviously (p < 0.05) inhibited by phenolics to
      varying degrees, and little influenced (p>0.05) by pasteurization, whereas
      sterilization initially accelerated WP digestion but did not change its overall
      digestibility.

PMID- 25577107
TI  - Production of rare sugars from common sugars in subcritical aqueous ethanol.
AB  - A new isomerization reaction was developed to synthesize rare ketoses. D
      tagatose, D-xylulose, and D-ribulose were obtained in the maximum yields of 24%,
      38%, and 40%, respectively, from the corresponding aldoses, D-galactose, D
      xylose, and D-ribose, by treating the aldoses with 80% (v/v) subcritical aqueous
      ethanol at 180 degrees C. The maximum productivity of D-tagatose was ca. 80
      g/(Lh). Increasing the concentration of ethanol significantly increased the
      isomerization of D-galactose. Variation in the reaction temperature did not
      significantly affect the production of D-tagatose from D-galactose. Subcritical
      aqueous ethanol converted both 2,3-threo and 2,3-erythro aldoses to the
      corresponding C-2 ketoses in high yields. Thus, the treatment of common aldoses
      in subcritical aqueous ethanol can be regarded as a new method to synthesize the
      corresponding rare sugars.

PMID- 25577108
TI  - Effect of beta-aminobutyric acid on cell wall modification and senescence in
      sweet cherry during storage at 20 degrees C.
AB  - The effects of postharvest beta-aminobutyric acid (BABA) treatment on fruit
      firmness, pectin degrading enzymes, cell wall constituents and microstructural
      alterations of pericarp in sweet cherry fruit were investigated. BABA
      significantly delayed the decline of fruit firmness and inhibited the increase of
      membrane permeability and the accumulation of malondialdehyde in cherries. The
      BABA-treated fruit exhibited significantly higher contents of water-soluble
      pectin, CDTA-soluble pectin, Na2CO3-soluble pectin, total pectin, cellulose and
      hemicellulose than the control during storage. Activities of pectin degrading
      enzymes including polygalacturonase and pectinmethylesterase were markedly
      reduced by BABA treatment. Observations by scanning electron microscopy showed
      BABA maintained smooth cuticle and integrated structure of subepidermal cell in
      sweet cherry. These results suggest that the delay in fruit senescence by BABA
      may be due to depressed membrane permeability and malondialdehyde content,
      reduced activities of polygalacturonase and pectinmethylesterase, enhanced cell
      wall polysaccharides content, and integrated subepidermal cell structure in sweet
      cherry. 

PMID- 25577109
TI  - Effect of physical state of gelatin-plasticizer based films on to the occurrence
      of Maillard reactions.
AB  - The aim of this study was to evaluate the occurrence of the Maillard reaction on
      gelatin-based films (bovine and salmon) in the glassy state, in mixtures with low
      molecular weight plasticizers (e.g. glycerol, glucose and trehalose) at different
      storage times. For testing, the gelatin-plasticizer films were stored under
      glassy conditions (Tg-10 degrees C), previously determined by calorimetric tests.
      Studies under accelerated conditions (T ? Tg) were also developed. Color, opacity
      and browning index (Br) were evaluated by computer vision at all storage times.
      Results showed in samples stored under glassy conditions that the Maillard
      reaction did not occur, independent of gelatin origin and type of plasticizer.
      Changes in color stated by opacity and Br were only significant (p < 0.05) in
      gelatin-glucose systems under accelerated storage conditions. The inhibition of
      reaction in gelatin films in the glassy state was related to the well-known
      conditions of low molecular mobility of glassy matrices, but also with the non
      Maillard reactive characteristics of glycerol and trehalose.

PMID- 25577110
TI  - D-glucose, D-galactose, and D-lactose non-enzyme quantitative and qualitative
      analysis method based on Cu foam electrode.
AB  - Here, D-glucose, D-galactose, and D-lactose non-enzyme quantitative and
      qualitative analysis method using Cu foam electrode had been investigated. Porous
      Cu foam material was prepared by electrodeposition strategy, and used as working
      electrode. Cyclic voltammetry (CV) explained sweetener electro-oxidation process
      occurring on Cu foam electrode. Amperometric i-t scanning results demonstrated
      that Cu foam electrode fast responded to D-glucose, D-galactose, and D-lactose in
      linear concentration range between 0.18 mM and 3.47 mM with significant
      sensitivity of 1.79 mA cm(-2)mM(-1), 0.57 mA cm(-2)mM(-1), and 0.64 mA cm(-2)mM(
      1), respectively. Limit of detection (LOD) was 9.30 MUM, 29.40 MUM, and 26 MUM
      respectively (S/N=3). Sweetener species was decided by stochastic resonance (SR)
      signal-to-noise ratio (SNR) eigen peak located noise intensities. Interference
      experiment results demonstrated that Cu foam electrode selectively responded to
      sweeteners against interference chemicals. The proposed method provides a
      promising way for sweetener non-enzyme quantitative and qualitative analysis.

PMID- 25577111
TI  - Synthetic analogues of flavonoids with improved activity against platelet
      activation and aggregation as novel prototypes of food supplements.
AB  - We investigated the ability of quercetin and apigenin to modulate platelet
      activation and aggregation, and compared the observed efficacy with that
      displayed by their synthetic analogues 2-phenyl-4H-pyrido[1,2-a]pyrimidin-4-ones,
      1-4, and 2,3-diphenyl-4H-pyrido[1,2-a]pyrimidin-4-ones, 5-7. Platelet aggregation
      was explored through a spectrophotometric assay on platelet-rich plasma (PRP)
      treated with the thromboxane A2 mimetic U46619, collagen and thrombin in
      presence/absence of various bioisosteres of flavonoids (12.5-25-50-100 MUM). The
      platelet density, (mean platelet component, MPC), was measured by the Advia 120
      Hematology System as a marker surrogate of platelet activation. The induced P
      selectin expression, which reflects platelet degranulation/activation, was
      quantified by flow cytometry on PRP. Our synthetic compounds modulated
      significantly both platelet activation and aggregation, thus turning out to be
      more effective than the analogues quercetin and apigenin when tested at a
      concentration fully consistent with their use in vivo. Accordingly, they might be
      used as food supplements to increase the efficacy of natural flavonoids.

PMID- 25577112
TI  - Coffee's country of origin determined by NMR: the Colombian case.
AB  - The determination of the origin of coffee beans by NMR fingerprinting has been
      shown promising and classification has been reported for samples of different
      countries and continents. Here we show that this technique can be extended and
      applied to discriminate coffee samples from one country against all others,
      including its closest neighbors. Very high classification rates are reported
      using a large number of spectra (>300) acquired over a two-year period. As
      original aspects it can be highlighted that this study was performed in fully
      automatic mode and with non-deuterated coffee extracts. This is achieved using a
      series of experiments to procure a robust suppression of the solvent peaks. As
      is, the method represents a cost effective opportunity for countries to protect
      their national productions. 

PMID- 25577113
TI  - A new cloud point extraction procedure for determination of inorganic antimony
      species in beverages and biological samples by flame atomic absorption
      spectrometry.
AB  - A new cloud-point extraction (CPE) for the determination of antimony species in
      biological and beverages samples has been established with flame atomic
      absorption spectrometry (FAAS). The method is based on the fact that formation of
      the competitive ion-pairing complex of Sb(III) and Sb(V) with Victoria Pure Blue
      BO (VPB(+)) at pH 10. The antimony species were individually detected by FAAS.
      Under the optimized conditions, the calibration range for Sb(V) is 1-250 MUg L(
      1) with a detection limit of 0.25 MUg L(-1) and sensitive enhancement factor of
      76.3 while the calibration range for Sb(III) is 10-400 MUg L(-1) with a detection
      limit of 5.15 MUg L(-1) and sensitive enhancement factor of 48.3. The precision
      as a relative standard deviation is in range of 0.24-2.35%. The method was
      successfully applied to the speciative determination of antimony species in the
      samples. The validation was verified by analysis of certified reference materials
      (CRMs).

PMID- 25577114
TI  - Antioxidant and antiproliferative activity of chokeberry juice phenolics during
      in vitro simulated digestion in the presence of food matrix.
AB  - Chokeberry juice was subjected to in vitro gastric digestion in the presence of
      food matrix in order to determine the changes in polyphenol content and
      antioxidant activity. Addition of food matrix immediately decreased the total
      phenolic content, anthocyanin content, DPPH scavenging activity as well as total
      reducing power by 36%, 90%, 45% and 44%, respectively. After in vitro digestion,
      total phenolic content, anthocyanin content and reducing power are slightly
      elevated, but they are still lower than in initial non-digested juice. The effect
      of digested juice on Caco-2 cells proliferation was also studied, and the
      reduction of proliferative rate by approximately 25% was determined. Our results
      suggested that although a large proportion of chokeberry phenolics undergo
      transformation during digestion they are still potent as antioxidant and
      antiproliferative agents. 

PMID- 25577115
TI  - A riboswitch sensor to determine vitamin B12 in fermented foods.
AB  - We describe a sensitive and selective method for determination of vitamin B12
      content in fermented foods using riboswitch sensor. A riboswitch amplicon from
      Propionibacterium freudenreichii was cloned in p519NGFP vector in Escherichia
      coli BL21 (DE3). The expression of green fluorescence protein was revers
      correlated to the concentrations of adenosylcobalamin. Adenosylcobalamin directly
      binds to riboswitch region leading to conformational changes in the secondary
      structure of mRNA, thus inhibiting expression. After various examinations, a
      standard curve was obtained from 10 to 1000 ng/mL of cyanocobalamin. The limit of
      determination is 10 ng/mL. The inter-assay coefficients of variation were 7.5%
      for the range of 10-1000 ng/mL. The recovery of this method was 92.3%. This
      method has no or less responses to nucleic acid, pseudovitamin B12, vitamin B12
      bound to intrinsic factor and haptocorrin. The riboswitch sensor results were
      similar with HPLC, but they were Ca. 24% lower than the microbiological assay
      results.

PMID- 25577116
TI  - Vitamin A Palmitate-beta-cyclodextrin inclusion complexes: characterization,
      protection and emulsification properties.
AB  - The interest in the production of foods enriched with vitamins, in order to
      prevent diseases related with their deficiency, has recently increased. However,
      the low stability and the low water solubility of certain vitamins make difficult
      their incorporation in foodstuff, especially in water-based formulations. This
      limitation is typically overcome by using encapsulating systems such as
      cyclodextrins. In this paper the formation of water-soluble inclusion complexes
      of Vitamin A Palmitate with beta-cyclodextrins, without the use of organic
      solvents, is described. The objective was to increase the water solubility of
      Vitamin A Palmitate and its stability against different external factors to
      eventually enrich aqueous-based products. The stability of Vitamin A Palmitate in
      the complexes towards temperature, oxygen and UV light was investigated. All
      results showed a notably increase of Vitamin A Palmitate water solubility and
      stability in front of those variables when encapsulated. The surface activity of
      the complex suggests its possible use as stabilizer in emulsion formulations. 

PMID- 25577117
TI  - Determination of essential and toxic elements in Hungarian honeys.
AB  - The aim of this present study was determination of essential and toxic element
      concentrations in 34 mono- and multi-floral honey samples from four geographical
      regions of Hungary, and examination of the connection between the floral origin
      and the element content. Ten elements (Al, Ca, Cu, Fe, K, Mg, Mn, P, S and Zn)
      were identified by ICP-OES and six (As, Cd, Cr, Mo, Pb, Se) were analysed by ICP
      MS. Potassium, calcium, and phosphorus were the most abundant elements with mean
      concentrations of 372, 47.9 and 44.3 mg kg(-1), respectively. The essential
      element content was very low in the analysed samples and generally below
      literature values. The concentrations of toxic elements were sufficiently low as
      to pose no risk to human health. The concentrations of aluminium, arsenic,
      cadmium and lead were low, with mean concentrations of 1028, 15.6, 0.746 and 45.5
      MUg kg(-1), respectively. Three honey groups (acacia, rape and sunflower) were
      distinguished by linear discriminant analysis from their element content.

PMID- 25577118
TI  - Quantification of nitropropanoyl glucosides in karaka nuts before and after
      treatment.
AB  - A high performance liquid chromatography (HPLC) method was developed to assay
      nitropropanoyl glucosides in the nuts of karaka (Corynocarpus laevigatus) a
      traditional food of New Zealand Maori. Levels of glucosides, measured as 3
      nitropropanoic acid, ranged from 50.25 to 138.62 g kg(-1) (5.0-13.9% w/w) and
      were highest in nuts from unripe drupes; these levels are higher than any
      previously reported. Other parts of the drupe also contained nitropropanoyl
      glucosides but at lower levels than the nut. Treatment procedures to remove the
      glucosides from the nuts varied in their efficacy with soxhlet extraction
      removing 98.7% and prolonged boiling and cold water extraction both removing 96%.
      These findings confirm the traditional methods for preparation of these nuts for
      consumption.

PMID- 25577119
TI  - Metal concentration and antioxidant activity of edible mushrooms from Turkey.
AB  - This study presents information on the antioxidant activity and heavy metal
      concentrations of Polyporus sulphureus, Macrolepiota procera, Lycoperdon perlatum
      and Gomphus clavatus mushrooms collected from the province of Mugla in the South
      Aegean Region of Turkey. Antioxidant activities of mushroom samples were
      evaluated by four complementary tests. All tests showed L. perlatum and G.
      clavatus to possess extremely high antioxidant potential. Antioxidant activity of
      the samples was strongly correlated with total phenolic-flavonoid content. In
      terms of heavy metal content, L. perlatum exceeded the legal limits for daily
      intake of Pb, Fe, Mn, Cr, Ni and Co contents (0.461, 738.00, 14.52, 1.27, 1.65,
      0.417 mg/day, respectively) by a 60-kg consumer. Co contents of M. procera (0.026
      mg/day) and P. sulphureus (0.030 mg/day) and Cd contents of G. clavatus (0.071
      mg/day) were also above the legal limits. According to these results, L. perlatum
      should not be consumed, despite the potentially beneficial antioxidant activity.
      Additionally, M. procera and G. clavatus should not be consumed daily due to
      their high levels of Cd and Co.

PMID- 25577120
TI  - Interactions of polyphenols with carbohydrates, lipids and proteins.
AB  - Polyphenols are secondary metabolites in plants, investigated intensively because
      of their potential positive effects on human health. Their bioavailability and
      mechanism of positive effects have been studied, in vitro and in vivo. Lately, a
      high number of studies takes into account the interactions of polyphenols with
      compounds present in foods, like carbohydrates, proteins or lipids, because these
      food constituents can have significant effects on the activity of phenolic
      compounds. This paper reviews the interactions between phenolic compounds and
      lipids, carbohydrates and proteins and their impact on polyphenol activity. 

PMID- 25577121
TI  - Evidence of oleuropein degradation by olive leaf protein extract.
AB  - The enzymatic activity of raw protein olive leaf extract has been investigated in
      vivo, on olive leaf homogenate and, in vitro with pure oleuropein and other
      phenolic substrates. At least two types of enzymes were found to be involved in
      the degradation of endogenous oleuropein in olive leaves. As for the in vitro
      experiments, the presence of active polyphenoloxidase and beta-glucosidase was
      determined by HPLC and UV-Visible spectroscopy. Interestingly, both the enzymatic
      activities were found to change during the storage of olive leaves. Specifically,
      the protein extracts obtained from fresh leaves showed the presence of both the
      enzymatic activities, because oleuropein depletion occurred simultaneously with
      the formation of the oleuropein aglycon, 3,4-DHPEA-EA. In comparison leaves
      subjected to the drying process showed a polyphenoloxidase activity leading
      exclusively to the formation of oxidation products responsible for the typical
      brown coloration of the reaction solution. 

PMID- 25577122
TI  - Physicochemical characteristics, polyphenol compositions and antioxidant
      potential of pomegranate juices from 10 Chinese cultivars and the environmental
      factors analysis.
AB  - Various pomegranate cultivars are grown in several regions of China, but
      comparative study of their juice polyphenols, antioxidant potentials, and health
      benefits are few. In the present study, physicochemical characteristics,
      polyphenol compositions, and antioxidant potentials of pomegranate aril juices
      from 10 cultivars in 4 Chinese regions were investigated. The results showed that
      the soluble solid content, reducing sugar content, titratable acid content of
      them were 13.97-16.30 degrees Brix, 62.82-110.70 g/L, 2.657-36.62 g/L,
      respectively. The total polyphenols, flavonoids, tannin and anthocyanin
      concentrations were 3.15-7.43 mg GaE/mL, 0.045-0.335 mg QuE/mL, 0.540-2.531 mg
      TaE/mL, and 0.004-0.160 mg CyE/mL, respectively. Sugar acid ratio, titratable
      acid content, total flavonoid concentration, and DPPH scavenging capacity were
      affected mainly by sweet and sour cultivar type, while soluble solid content and
      total anthocyanin concentration were affected by environment. Temperature in
      maturity period and latitude of growing region significantly effected on
      polyphenol and antioxidant potential levels of pomegranate juice.

PMID- 25577123
TI  - Simultaneous detection of multi-allergens in an incurred food matrix using ELISA,
      multiplex flow cytometry and liquid chromatography mass spectrometry (LC-MS).
AB  - Food allergy is a public health concern and an important food safety issue. Food
      allergies affect up to 6% of infants and children and 4% of adults. The objective
      of this work was to determine differences in the detection of single and multiple
      allergens (i.e., casein, soy protein, and gluten) in an incurred food matrix
      before and after baking. Cookies were used as a model food system. Three methods,
      namely, multiplex assay (a new optimized method based on flow cytometry for
      multiple allergen analysis), enzyme-linked immunosorbent assay (ELISA) using
      commercial kits and LC-MS were used to detect allergens in the samples before and
      after baking. The ELISA kits performed well in detecting allergens in the raw
      samples with recoveries of 91-108%, 88-127% and 85-108% for casein, soy protein
      and gluten, respectively. Recoveries were poor for the baked cookies (67-90%, 66
      95% and 66-88% for casein, soy protein and gluten, respectively). The multiplex
      flow cytometry assay permitted multiple allergen detection in the raw samples,
      with the following recoveries based on soluble protein: casein, 95-107%; soy
      protein, 92-97%, and gluten, 96-99%. Data for the baked cookies were as follows:
      casein, 84-90%; soy protein, 80-88%, and gluten, 80-90%. The LC-MS technique
      detected marker peptides that could be used to identify allergens in the baked
      food samples up to concentrations of 10 ppm for casein and soy protein, and 100
      ppm for gluten. To the best of our knowledge, the current study is the first to
      compare ELISA, LC-MS and multiplex flow cytometry methods for the detection of
      multiple allergens simultaneously incurred in a model food system.

PMID- 25577124
TI  - Antioxidant activities of tocopherols/tocotrienols and lipophilic antioxidant
      capacity of wheat, vegetable oils, milk and milk cream by using
      photochemiluminescence.
AB  - The purpose of this study was to measure the antioxidant activity (AOA) of
      tocopherols and tocotrienols by using photochemiluminescence (PCL). This method
      enables to detect total lipophilic antioxidants. The AOA of all vitamin E isomers
      depended on number and position of methyl groups in the chroman ring. Correlation
      between the AOA and the redox potential and the biological activity of the
      tocochromanols was observed. The second aim was to analyse different kinds of
      wheat, vegetable oils, milk and milk cream on their antioxidant capacity (AOC) by
      using PCL and alpha-TEAC. The contents of vitamin E and carotenoids were analysed
      by HPLC. Correlations between the sum of carotenoids and vitamin E and the AOC
      were detected. Based on high vitamin E contents, the oils had the highest and in
      contrast, the product macaroni showed the lowest AOC. A concentration-dependent
      effect was observed in both assays, PCL and alpha-TEAC. 

PMID- 25577125
TI  - A Caco-2 cell-based quantitative antioxidant activity assay for antioxidants.
AB  - A Caco-2 cell-based antioxidant activity (CAA) assay for quantitative evaluation
      of antioxidants was developed by optimizing seeding density and culture time of
      Caco-2 cells, incubation time and concentration of fluorescent probe (2',7'
      dichlorofluorescin diacetate, DCFH-DA), incubation way and incubation time of
      antioxidants (pure phytochemicals) and DCFH-DA with cells, and detection time of
      fluorescence. Results showed that the CAA assay was of good reproducibility and
      could be used to evaluate the antioxidant activity of antioxidants at the
      following conditions: seeding density of 5 * 10(4)/well, cell culture time of
      24h, co-incubation of 60 MUM DCFH-DA and pure phytochemicals with Caco-2 cells
      for 20 min and fluorescence recorded for 90 min. Additionally, a significant
      correlation was observed between CAA values and rat plasma ORAC values following
      the intake of antioxidants for selected pure phytochemicals (R(2) = 0.815, p <
      0.01), demonstrating the good biological relevance of CAA assay.

PMID- 25577126
TI  - Impact of US Brown Swiss genetics on milk quality from low-input herds in
      Switzerland: interactions with grazing intake and pasture type.
AB  - This study investigated the effect of, and interactions between, contrasting
      crossbreed genetics (US Brown Swiss [BS] * Improved Braunvieh [BV] * Original
      Braunvieh [OB]) and feeding regimes (especially grazing intake and pasture type)
      on milk fatty acid (FA) profiles. Concentrations of total polyunsaturated FAs,
      total omega-3 FAs and trans palmitoleic, vaccenic, alpha-linolenic,
      eicosapentaenoic and docosapentaenoic acids were higher in cows with a low
      proportion of BS genetics. Highest concentrations of the nutritionally desirable
      FAs, trans palmitoleic, vaccenic and eicosapentaenoic acids were found for cows
      with a low proportion of BS genetics (0-24% and/or 25-49%) on high grazing intake
      (75-100% of dry matter intake) diets. Multivariate analysis indicated that the
      proportion of OB genetics is a positive driver for nutritionally desirable
      monounsaturated and polyunsaturated FAs while BS genetics proportion was positive
      driver for total and undesirable individual saturated FAs. Significant genetics *
      feeding regime interactions were also detected for a range of FAs.

PMID- 25577127
TI  - Vitamin D deficiency is associated with pulmonary dysfunction in cystic fibrosis.
AB  - BACKGROUND: Vitamin D deficiency is common in CF. Whether vitamin D affects
      pulmonary function in CF is unknown. METHODS: Data were abstracted from
      clinically stable CF patients who had pulmonary function studies and serum 25
      hydroxyvitamin D [25(OH)D, ng/ml] levels drawn within 2 months of each other.
      Findings were adjusted for multiple variables known to affect pulmonary function
      in CF. RESULTS: Enrollees totaled 597. Overall mean 25(OH)D level was 29.6+/-12.8
      ng/ml (SD). Serum 25(OH)D levels showed a significant correlation with forced
      expiratory volume in 1s (FEV1) % predicted (r=0.20, p<0.0001) and forced vital
      capacity % predicted (r=0.13, p=0.0019). Multivariate analysis revealed that
      serum 25(OH)D remained an independent predictor of FEV1 % predicted even after
      controlling for multiple other factors known to affect CF lung function.
      CONCLUSIONS: Serum 25(OH)D levels are significantly associated with pulmonary
      function in CF. Further study is required to determine whether this association
      is causal.

PMID- 25577128
TI  - The reputation of punishers.
AB  - Punishment is a potential mechanism to stabilise cooperation between self
      regarding agents. Theoretical and empirical studies on the importance of a
      punitive reputation have yielded conflicting results. Here, we propose that a
      variety of factors interact to explain why a punitive reputation is sometimes
      beneficial and sometimes harmful. We predict that benefits are most likely to
      occur in forced play scenarios and in situations where punishment is the only
      means to convey an individual's cooperative intent and willingness to uphold
      fairness norms. By contrast, if partner choice is possible and an individual's
      cooperative intent can be inferred directly, then individuals with a nonpunishing
      cooperative reputation should typically be preferred over punishing cooperators. 

PMID- 25577129
TI  - Proteomic analysis of urethral protein expression in an estrogen receptor alpha
      deficient murine model of stress urinary incontinence.
AB  - PURPOSE: The roles of estrogen receptor alpha (ERalpha) in stress urinary
      incontinence (SUI) remain elusive. This study was conducted to understand the
      molecular mechanism of ERalpha against SUI. METHODS: Wild-type (ERalpha(+/+)) and
      ACTB-cre ERalpha knockout (ERalpha(-/-)) female mice were generated. Urethral
      function and protein expression were measured. Leak point pressures (LPP) and
      maximum urethral closure pressure (MUCP) were assessed in mice under urethane
      anesthesia. After the measurements, the urethras were removed for proteomic
      analysis using the two-dimensional differential gel electrophoresis and liquid
      chromatography-mass spectrometry technology. Interaction between these ERalpha
      pathway proteins was further analyzed by using MetaCore. Lastly, Western blot and
      immunochemistry (IHC) were used to confirm the candidate protein expression
      levels and locations, respectively. RESULTS: Compared with the ERalpha(+/+)
      group, the LPP and MUCP values of the ERalpha(-/-) group were significantly
      decreased. Additionally, we identified 11 differentially expressed proteins in
      the urethra of ERalpha(-/-) female mice; five proteins were down-regulated and
      six were up-regulated. The majority of the ERalpha knockout-modified proteins
      were involved in muscle development, contraction, and regulation, as well as
      immune response (amphoterin signaling and phagocytosis), proteolysis, and cell
      adhesion (platelet aggregation and integrin-mediated cell-matrix adhesion). IHC
      and Western blot confirmed the down-regulation of tropomyosin and up-regulation
      of myosin in urethra. CONCLUSIONS: This is the first study to estimate protein
      expression changes in urethras from ERalpha(-/-) female mice. These changes could
      be related to the molecular mechanism of ERalpha in SUI.

PMID- 25577130
TI  - Significant increase in detection of prostate cancer recurrence following radical
      prostatectomy with an early imaging acquisition protocol with 18F-fluorocholine
      positron emission tomography/computed tomography.
AB  - PURPOSE: To highlight a new imaging acquisition protocol during (18)F
      fluorocholine PET/CT in patients with biochemical recurrence after RP. METHODS: A
      total of 146 patients with PSA levels between 0.2 and 1 ng/ml with negative
      conventional imaging who did not receive salvage treatment were prospectively
      enrolled. Imaging acquisition protocol included an early dynamic phase (1-8 min),
      a conventional whole body (10-20 min), and a late phase (30-40 min). Sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      were measured. Univariable and multivariable analyses were performed to identify
      independent predictors of positive PET/CT. RESULTS: The median trigger PSA was
      0.6 ng/ml (IQR 0.43-0.76). Median PSA doubling time (PSA DT) was 7.91 months (IQR
      4.42-11.3); median PSA velocity (PSAV) was 0.02 ng/ml per month (IQR 0.02-0.04).
      Overall, (18)F-fluorocholine PET/CT was positive in 111 of 146 patients (76 %).
      Out of 111 positive examinations, 80 (72.1 %) were positive only in the early
      dynamic phase. Sensitivity, specificity, PPV, NPV, and accuracy were 78.9, 76.9,
      97.2, 26.3, and 78.7 %, respectively. At multivariable logistic regression,
      trigger PSA >= 0.6 ng/ml [odds ratio (OR) 3.13; p = 0.001] and PSAV >= 0.04 ng/ml
      per month (OR 4.95; p = 0.004) were independent predictors of positive PET/CT.
      The low NPV remains the main limitation of PET/CT in this setting of patients.
      CONCLUSIONS: The increased sensitivity, thanks to the early imaging acquisition
      protocol, makes (18)F-fluorocholine PET/CT an attractive tool to detect prostate
      cancer recurrences in patients with a PSA level <1 ng/ml.

PMID- 25577131
TI  - Fifteen-year single-centre experience with three different surgical procedures of
      nerve-sparing cystectomy in selected organ-confined bladder cancer patients.
AB  - OBJECTIVES: To evaluate technical feasibility and oncologic and functional
      outcomes of three different surgical procedures of nerve-sparing radical
      cystectomy (NS-RC) for the treatment of organ-confined bladder cancer at a single
      referral centre. MATERIALS AND METHODS: All consecutive cases of NS-RC carried
      out between 1997 and 2012 were retrospectively analysed. NS-RC included nerve
      sparing cysto-vesicleprostatectomy (NS-CVP), capsule-sparing cystectomy (CS-C)
      and seminal-sparing cysto-prostatectomy (SS-CP). Peri-operative parameters and
      post-operative outcomes were analysed. RESULTS: Overall, 90 patients underwent NS
      RC, 35 (38.9 %) of whom received a NS-CVP, while 36 (40 %) and 19 (21.1 %)
      underwent capsule CS-C and SS-CP, respectively. No difference was registered
      comparing oncologic outcomes of the three different techniques; however, two
      local recurrences after CS-C were attributed to the surgical technique. Complete
      post-operative daytime and night-time urinary continence (UC) at 24 and 48 months
      was achieved in 94.4 and 74.4 % and in 88.8 and 84.4 % of cases, respectively. CS
      C showed both the best UC and sexual function preservation rate at early follow
      up (24 months). Overall, a satisfactory post-operative erectile function (IIEF-5
      >= 22) was proved in 57 (68.6 %) and 54 (65.0 %) patients at 24 and 48 months,
      respectively. Significant difference was found when comparing sexual function
      preservation rate of NS-CVP (28.5 %) to that of CS-C (91.6 %) and SS-CP (84.2 %).
      CONCLUSION: NS-RC for male patients accounted for 7.4 % of overall radical
      cystectomy. To a limited extent of the selected organ-confined bladder cancers
      treated, the three different procedures analysed showed comparable results in
      terms of local recurrence and cancer-specific survival. Both CS-C and SS-CP
      procedures provided excellent functional outcomes when compared to original NS
      CVP.

PMID- 25577132
TI  - Gas exchange and lung mechanics in patients with acute respiratory distress
      syndrome: comparison of three different strategies of positive end expiratory
      pressure selection.
AB  - PURPOSE: The purpose of the study was to compare gas exchange and lung mechanics
      between different strategies to select positive end-expiratory pressure (PEEP) in
      acute respiratory distress syndrome (ARDS). METHODS: In 20 consecutive ARDS
      patients, 3 PEEP selection strategies were evaluated. One strategy was based on
      oxygenation using the ARDS network PEEP/fraction of inspired oxygen (Fio2) table;
      and two were based on lung mechanics, either PEEP titrated to reach a plateau
      pressure of 28 to 30 cm H2O as in the ExPress trial or best respiratory
      compliance method during a derecruitment maneuver. Gas exchange, airway
      pressures, stress index (SI), and end-expiratory transpulmonary pressure (P(tpe))
      and end-inspiratory transpulmonary pressure (P(tpi)) values were assessed. Data
      are expressed as median (interquartile range [IQR]). RESULTS: Lower total PEEP
      levels were observed with the use of the PEEP/Fio2 table (8.7 [6-10] cm H2O);
      intermediate PEEP levels, with the Best Compliance approach (13.0 [10.2-13.8] cm
      H2O); and higher PEEP levels, with the ExPress strategy (16.5 [15.0-18.5] cm H2O)
      (P < .01). Pao2/Fio2 ratio was lower with the PEEP/Fio2 table. Oxygenation with
      Best Compliance approach and ExPress strategy was not different with lower
      plateau pressure in the former (23 [20-25] vs 30 [29-30] cm H2O; P < .01). Paco2
      was slightly higher with the ExPress method than the others 2 strategies.
      Negative P(tpe) was observed in 35% of the patients with the PEEP/Fio2 table, in
      15% applying the Best Compliance, and in only 1 case with the ExPress method.
      Higher SI and P(tpi), with lower lung compliance, were obtained with ExPress
      strategy. CONCLUSIONS: Using a best respiratory compliance approach resulted in
      better oxygenation levels without risk of overdistension according to SI and
      P(tpi), achieving a mild risk of lung collapse according to P(tpe).

PMID- 25577133
TI  - Phase I study of nanoliposomal irinotecan (PEP02) in advanced solid tumor
      patients.
AB  - PURPOSE: To define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD)
      and pharmacokinetics (PK) of PEP02, a novel liposome-encapsulated irinotecan, in
      patients with advanced refractory solid tumors. METHODS: Patients were enrolled
      in cohorts of one to three to receive escalating dose of PEP02 in a phase I
      trial. PEP02, from 60 to 180 mg/m(2), was given as a 90-min intravenous infusion,
      every 3 weeks. RESULTS: A total of 11 patients were enrolled into three dose
      levels: 60 (one patient), 120 (six patients) and 180 mg/m(2) (four patients). DLT
      was observed in three patients, one at 120 mg/m(2) (grade 3 catheter-related
      infection) and two at 180 mg/m(2) (grade 4 neutropenia lasting for >3 days in
      one, grade 4 hematological toxicities and grade 4 diarrhea in the other). MTD was
      determined as 120 mg/m(2). Comparing with those after free-form irinotecan in the
      literature, the dose-normalized PK of SN-38 (the active metabolite) after PEP02
      was characterized by lower C max, prolonged terminal half-life and higher AUC but
      with significant inter-individual variation. One patient who died of treatment
      related toxicity had significantly higher C max and AUC levels of SN-38 than
      those of the other three patients at 180 mg/m(2). Post hoc pharmacogenetic study
      showed that the patient had a combined heterozygosity genotype of UGT1A1*6/*28.
      Two patients had objective tumor response. CONCLUSIONS: PEP02 apparently modified
      the PK parameters of irinotecan and SN-38 by liposome encapsulation. The MTD of
      PEP02 monotherapy at 3-week interval is 120 mg/m(2), which will be the
      recommended dose for future studies.

PMID- 25577134
TI  - A dose-escalation study of oxaliplatin/capecitabine/irinotecan (XELOXIRI) and
      bevacizumab as a first-line therapy for patients with metastatic colorectal
      cancer.
AB  - PURPOSE: The aim of this study was to determine the recommended dose (RD) of a
      triweekly capecitabine, oxaliplatin, irinotecan, and bevacizumab
      (XELOXIRI/bevacizumab) regimen that was easier to administer than
      FOLFOXIRI/bevacizumab, using capecitabine instead of 5-fuorouracil (5-FU), in
      patients with metastatic colorectal cancer (mCRC). METHODS: Patients received
      oxaliplatin (100 mg/m(2), day 1), capecitabine (1,700 mg/m(2) per day from day 2
      to 15), irinotecan (100, 120, 150 mg/m(2) for dose levels 1, 2, 3, day 1), and
      bevacizumab (7.5 mg/kg, day 1), repeated every 3 weeks. Dose-limiting toxicities
      (DLTs) were assessed in the first two cycles to determine the maximum tolerated
      dose (MTD). RESULTS: Twelve patients received a median of 6.5 cycles of therapy
      (range 2-12). The DLT was grade 4 neutropenia, observed in one of six patients at
      dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of
      irinotecan was defined as 150 mg/m(2). The most common grade >=3 toxicities were
      neutropenia (41 %), anemia (17 %), diarrhea (8 %), and febrile neutropenia (8 %).
      The response rate and median progression-free survival were 83 % and 15 months,
      respectively. CONCLUSIONS: XELOXIRI/bevacizumab is a feasible regimen for
      patients with mCRC, neutropenia was the DLT, and the RD of irinotecan is 150
      mg/m(2). The response rate observed is very promising and warrants further
      investigation.

PMID- 25577135
TI  - Increasing incidence of acute kidney injury: also a problem in pregnancy?

PMID- 25577136
TI  - New insights into gastrointestinal anthrax infection.
AB  - Bacterial infections are the primary cause of gastrointestinal (GI) disorders in
      both developing and developed countries, and are particularly dangerous for
      infants and children. Bacillus anthracis is the 'archetype zoonotic' pathogen; no
      other infectious disease affects such a broad range of species, including humans.
      Importantly, there are more case reports of GI anthrax infection in children than
      inhalational disease. Early diagnosis is difficult and widespread systemic
      disease develops rapidly. This review highlights new findings concerning the
      roles of the gut epithelia, commensal microbiota, and innate lymphoid cells
      (ILCs) in initiation of disease and systemic dissemination in animal models of GI
      anthrax, the understanding of which is crucial to designing alternative therapies
      that target the establishment of infection. 

PMID- 25577138
TI  - Increased recruitment of bone marrow-derived cells into the brain associated with
      altered brain cytokine profile in senescence-accelerated mice.
AB  - Bone marrow-derived cells enter the brain in a non-inflammatory condition through
      the attachments of choroid plexus and differentiate into ramified myeloid cells.
      Neurodegenerative conditions may be associated with altered immune-brain
      interaction. The senescence-accelerated mouse prone 10 (SAMP10) undergoes earlier
      onset neurodegeneration than C57BL/6 (B6) strain. We hypothesized that the
      dynamics of immune cells migrating from the bone marrow to the brain is perturbed
      in SAMP10 mice. We created 4 groups of radiation chimeras by intra-bone marrow
      bone marrow transplantation using 2-month-old (2 mo) and 10 mo SAMP10 and B6 mice
      as recipients with GFP transgenic B6 mice as donors, and analyzed histologically
      4 months later. In the [B6 -> 10 mo SAMP10] chimeras, more ramified marrow
      derived cells populated a larger number of discrete brain regions than the other
      chimeras, especially in the diencephalon. Multiplex cytokine assays of the
      diencephalon prepared from non-treated 3 mo and 12 mo SAMP10 and B6 mice revealed
      that 12 mo SAMP10 mice exhibited higher tissue concentrations of CXCL1, CCL11, G
      CSF, CXCL10 and IL-6 than the other groups. Immunohistologically, choroid plexus
      epithelium and ependyma produced CXCL1, while astrocytic processes in the
      attachments of choroid plexus expressed CCL11 and G-CSF. The median eminence
      produced CXCL10, hypothalamic neurons G-CSF and tanycytes CCL11 and G-CSF. These
      brain cytokine profile changes in 12 mo SAMP10 mice were likely to contribute to
      acceleration of the dynamics of marrow-derived cells to the diencephalon. Further
      studies on the functions of ramified marrow-derived myeloid cells would enhance
      our understanding of the brain-bone marrow interaction.

PMID- 25577139
TI  - Liver metastasis of ethmoid sinus adenocarcinoma.
AB  - INTRODUCTION: Sinonasal cancer is an uncommon neoplasm, often associated with
      exposure to occupational hazards and delayed diagnosis. CASE REPORT: The authors
      report a rare case of solitary liver metastasis from ethmoid sinus adenocarcinoma
      treated by surgical resection. No clinical or radiological sign of recurrence was
      observed with a follow-up of 3 months. DISCUSSION: Adenocarcinoma of the ethmoid
      sinus is characterized by its aggressiveness and its tendency to recurrence.
      Metastases are rare and can be found in unexpected organs due to dissemination
      via collateral venous plexuses. The role of chemotherapy has not been clearly
      established. Due to their rarity, the treatment of metastases has not yet been
      defined.

PMID- 25577140
TI  - Is it time for a paradigm shift in understanding embryo selection?
AB  - BACKGROUND: Embryo selection has been an integral feature of in vitro
      fertilization (IVF) almost since its inception. Since the advent of extended
      blastocyst stage embryo culture, and especially with increasing popularity of
      elective single embryo transfer (eSET), the concept of embryo selection has
      increasingly become a mainstay of routine IVF. DISCUSSION: We here, however,
      argue that embryo selection via blastocyst stage embryo transfer (BSET), as
      currently practiced, at best improves IVF outcomes only for a small minority of
      patients undergoing IVF cycles. For a large majority BSET is either ineffective
      or, indeed, may actually be harmful by decreasing IVF pregnancy chances. Overall,
      only a small minority of patients, thus, benefit from prolonged embryo culture,
      while BSET, as a tool to enhance IVF outcomes, is increasingly utilized as
      routine care in IVF for all patients. SUMMARY: Since newer methods of embryo
      selection, like preimplantation genetic screening (PGS) and closed system embryo
      incubation with time-lapse photography are practically dependent on BSET, these
      concepts of embryo selection, currently increasingly adopted in mainstream IVF,
      require reconsideration. They, automatically, transfer the downsides of BSET,
      including decreases in IVF pregnancy chances in some patients, to these new
      procedures, and in addition raise serious questions about cost-effectiveness.

PMID- 25577137
TI  - Preserved emotional awareness of pain in a patient with extensive bilateral
      damage to the insula, anterior cingulate, and amygdala.
AB  - Functional neuroimaging investigations of pain have discovered a reliable pattern
      of activation within limbic regions of a putative "pain matrix" that has been
      theorized to reflect the affective dimension of pain. To test this theory, we
      evaluated the experience of pain in a rare neurological patient with extensive
      bilateral lesions encompassing core limbic structures of the pain matrix,
      including the insula, anterior cingulate, and amygdala. Despite widespread damage
      to these regions, the patient's expression and experience of pain was intact, and
      at times excessive in nature. This finding was consistent across multiple pain
      measures including self-report, facial expression, vocalization, withdrawal
      reaction, and autonomic response. These results challenge the notion of a "pain
      matrix" and provide direct evidence that the insula, anterior cingulate, and
      amygdala are not necessary for feeling the suffering inherent to pain. The
      patient's heightened degree of pain affect further suggests that these regions
      may be more important for the regulation of pain rather than providing the
      decisive substrate for pain's conscious experience. 

PMID- 25577141
TI  - Thrombelastographic pattern recognition in renal disease and trauma.
AB  - BACKGROUND: Thrombelastography (TEG) is a viscoelastic hemostatic assay. We have
      observed that end-stage renal disease (ESRD) and trauma-induced coagulopathy
      (TIC) produce distinctive TEG tracings. We hypothesized that rigorously definable
      TEG patterns could discriminate between healthy controls and patients with ESRD
      and TIC. METHODS: TEG was performed on blood from ESRD patients (n = 54) and
      blood from trauma patients requiring a massive blood transfusion (n = 16). Plots
      of independent TEG parameters were analyzed for patterns coupled to disease
      state, compared with controls. Decision trees for taxonomic classification were
      then built using the "R-Project" statistical software. RESULTS: Minimally
      overlapping clusters of TEG results were observed for the three patient groups
      when coordinate pairs of maximum amplitude (MA) and TEG-activated clotting time
      (ACT) were plotted on orthogonal axes. Based on these groupings, a taxonomical
      classification tree was constructed using MA and TEG ACT. Branch points were set
      at an ACT of 103 s, and these branches subdivided for MA at 60.8 mm for the high
      ACT branch and 72.6 mm for the low ACT branch, providing a correct classification
      rate of 93.4%. CONCLUSIONS: ESRD and TIC demonstrate distinct TEG patterns. The
      coagulopathy of ESRD is typified by a prolonged enzymatic phase of clot
      formation, with normal-to-elevated final clot strength. Conversely, TIC is
      typified by prolonged clot formation and weakened clot strength. Our taxonomic
      categorization constitutes a rigorous system for the algorithmic interpretation
      of TEG based on cluster analysis. This will form the basis for clinical decision
      support software for viscoelastic hemostatic assays.

PMID- 25577142
TI  - Prognostic value of the platelet to lymphocyte ratio change in liver cancer.
AB  - BACKGROUND: There is limited evidence concerning the postoperative platelet to
      lymphocyte ratio change (DeltaPLR) in relation to the prognosis of hepatocellular
      carcinoma (HCC). This study was designed to evaluate the prognostic value of
      DeltaPLR in patients with hepatitis B virus (HBV)-related small HCC who underwent
      liver resection. MATERIALS AND METHODS: We retrospectively reviewed 219 patients
      with HBV-related small HCC who underwent liver resection between February 2007
      and April 2013. The patients were divided into two groups as follows: group A
      (DeltaPLR >=2.875, n = 94) and group B (DeltaPLR <2.875, n = 125), according to
      receiver operating characteristic analysis. Demographic, clinical, and follow-up
      data were analyzed, and multivariate analysis was used to identify prognostic
      factors. RESULTS: The 1-, 3-, and 5-y overall survival (OS) rates were 90.5%,
      72.3%, and 42.1%, respectively, in group A and 98.1%, 89.5%, and 86.4%,
      respectively, in group B (P < 0.001). Correspondingly, the 1-, 3-, and 5-y
      recurrence-free survival (RFS) rates were 57.5%, 36.1%, and 22.8%, respectively,
      in group A and 84.3%, 62.4%, and 55.4%, respectively, in group B (P < 0.001).
      Multivariate analysis showed that DeltaPLR was an independent prognostic factor
      for both OS (P < 0.001, hazard ratio = 5.452, 95% confidence interval 2.592
      11.467) and RFS (P < 0.001, hazard ratio = 2.191, 95% confidence interval 1.4611
      3.288). CONCLUSIONS: DeltaPLR was an independent prognostic factor for OS and RFS
      in patients with HBV-related small HCC who underwent liver resection.

PMID- 25577143
TI  - Penehyclidine hydrochloride postconditioning on lipopolysaccharide-induced acute
      lung injury by inhibition of inflammatory factors in a rodent model.
AB  - BACKGROUND: Sepsis is associated with acute lung injury (ALI) and high mortality.
      The aim of this study was to investigate the effects of different doses of
      penehyclidine hydrochloride (PHC) postconditioning on ALI induced by sepsis in a
      rat model. METHODS: A rat model of ALI was induced by intravenous injection of
      lipopolysaccharide (LPS). The different doses of PHC were administrated
      intravenously at 30 min after LPS administration (low dose, 0.3 mg/kg; medium
      dose, 1.0 mg/kg, and high dose, 3.0 mg/kg). After 6 h, arterial blood samples
      were obtained for blood gas analyses. Meanwhile, lung tissue was harvested and
      lung injury was assessed by the histopathologic changes (hematoxylin and eosin
      staining) and wet-to-dry lung weight ratio. The tumor necrosis factor-alpha and
      interleukin-6 levels in bronchoalveolar lavage fluid, as well as the nuclear
      factor-kappa B protein expressions, and the myeloperoxidase activities in lung
      tissues were measured by immunohistochemistry or enzyme-linked immunosorbent
      assay, respectively. RESULTS: LPS-induced severe lung injury evidenced by
      increased pathologic scores and lung wet-to-dry weight ratio, which was
      accompanied by increases in the expression of pulmonary nuclear factor-kappa B
      protein and the activity of pulmonary myeloperoxidase and the levels of
      interleukin-6 and tumor necrosis factor-alpha in bronchoalveolar lavage fluid.
      The arterial oxygen tension (PaO2), pH, and the PaO2/fraction of inspired oxygen
      ratio (PaO2/FiO2) decreased significantly and the carbon dioxide tension (PaCO2)
      increased notedly after an LPS injection. All doses of PHC could significantly
      ameliorate lung injury and improve the previously mentioned variables (P < 0.05
      or 0.01). Furthermore, the protection of medium dose (1.0 mg/kg) could be better
      than that of low or high dose. CONCLUSIONS: These findings indicated that
      different doses of PHC, especially to medium dose, could prevent LPS-induced ALI
      in rats, at least in part, by inhibiting inflammatory response. Moreover, the
      protection of pharmacologic postconditioning with PHC is limited by a "ceiling
      effect."

PMID- 25577144
TI  - Hypercapnic acidosis prolongs survival of skin allografts.
AB  - BACKGROUND: Evidence reveals that hypercapnic acidosis (HCA) modulates immune
      responses. However, the effect of HCA on allogenic skin graft rejection is
      unknown. We examined whether HCA might improve skin graft survival in a mouse
      model of skin transplantation. METHODS: A major histocompatibility-complex
      incompatible BALB/c to C57BL/6 mouse skin transplantation model was used. Animals
      were divided into sham control, air, and HCA groups. Mice in the HCA group were
      exposed daily to 5% CO2 in air for 1 h. Skin grafts were harvested for histologic
      analyses. Nuclear factor (NF)-kappaB activation was determined in harvested
      draining lymph nodes. Spleen weights and serum levels of tumor necrosis factor
      alpha and chemokine (C-X-C motif) ligand 2 were serially assessed after skin
      transplantation. RESULTS: Skin allografts survived significantly longer in the
      HCA group of mice than those in the air group. Allografted mice in the air group
      underwent a 2.1-fold increase in spleen weight compared with a 1.1-fold increase
      in the mice with HCA on day 3. There were increased inflammatory cell
      infiltration, folliculitis, focal dermal-epidermal separation, and areas of
      epidermal necrosis in the air group that were reduced with HCA treatment. In the
      HCA group, CD8(+) T cell infiltration at day 7 decreased significantly but not
      CD4(+) T cell infiltration. In addition, HCA significantly suppressed serum tumor
      necrosis factor-alpha on days 1 and 3 and chemokine (C-X-C motif) ligand 2 on
      days 1 and 10. Furthermore, the HCA group had remarkably suppressed NF-kappaB
      activity in draining lymph nodes. CONCLUSIONS: HCA significantly prolonged the
      survival of incompatible skin allografts in mice by reducing proinflammatory
      cytokine production, immune cell infiltration, and NF-kappaB activation.

PMID- 25577145
TI  - Intraoperative ventilation strategy during cardiopulmonary bypass attenuates the
      release of matrix metalloproteinases and improves oxygenation.
AB  - BACKGROUND: Patients undergoing open heart surgery with cardiopulmonary bypass
      (CPB) often develop a systemic immune reaction, characterized by an increase of
      proinflammatory and anti-inflammatory mediators. We previously demonstrated that
      continued mechanical ventilation during CPB reduces this response. We
      hypothesized that this strategy may also impact on matrix metalloproteinase (MMP)
      release. MATERIAL AND METHODS: Thirty consecutive patients undergoing coronary
      artery bypass grafting with CPB were randomized into a ventilated (VG) (n = 15)
      and a standard non-ventilated group (NVG) (n = 15). Blood was collected at the
      beginning, at the end of surgery, and on the five consecutive days. MMPs, tissue
      inhibitor of matrix metalloproteinase 1 (TIMP-1), and lipocalin 2 (LCN2) were
      measured by enzyme-linked immunosorbent assay. Parameters of transpulmonary
      oxygen transport were assessed at different time points. RESULTS: MMP-8, MMP-9,
      and LCN2 were significantly lower at the end of surgery in VG compared with those
      in NVG patients (MMP-8 [ng/mL]: 7.1 [3.5] versus 12.5 [7.7], P = 0.02; MMP-9
      [ng/mL]: 108 [42] versus 171 [98], P = 0.029; LCN2 [ng/mL]: 109 [42] versus 171
      [98], P = 0.03). TIMP-1 concentrations were lower on postoperative day one, (TIMP
      1 [ng/mL]: 174 [55] versus 273 [104], P = 0.003), whereas MMP-3 levels were lower
      on postoperative days four and five (MMP-3 [ng/mL]: 44 [17] versus 67 [35], P =
      0.026). The arterial partial pressure of oxygen/fraction of inspired oxygen ratio
      was significantly higher in VG patients throughout the postoperative observation
      period, which did not affect the length of postoperative ventilatory support.
      CONCLUSIONS: Continued mechanical ventilation during CPB reduces serum levels of
      MMPs, their inhibitor TIMP-1 and LCN2, which preserves MMP-9 activity. The
      present study suggests that continued mechanical ventilation improves
      postoperative oxygenation and could potentially prevent aggravation of lung
      injury after CPB.

PMID- 25577146
TI  - Angiogenic and growth factors in gastric cancer.
AB  - BACKGROUND: Antiangiogenic treatment is at the horizon in the palliative
      treatment of gastric cancer (GC), but data on proangiogenic biomarkers are still
      limited. The aim of this study was to analyze five proteins with a function in
      tumor angiogenesis: vascular endothelial growth factor (VEGF), angiopoietin-2
      (Ang-2), follistatin, leptin, and platelet endothelial cell adhesion molecule 1
      (CD31) in peripheral blood and corresponding tumor tissue. MATERIAL AND METHODS:
      From 2008-2010, tumor tissue (n = 76) and corresponding preoperative serum (n =
      69) of patients with localized GC were collected; 45 had perioperative
      chemotherapy. Protein serum or tumor lysate levels of these factors were measured
      by an angiogenesis multiplex immunoassay and correlated with response and
      survival. RESULTS: Serum Ang-2 had prognostic relevance in the whole study
      population (P = 0.027). In subgroup analysis, serum VEGF and Ang-2 had prognostic
      relevance in primarily resected patients (P = 0.028; P = 0.048) but no
      association was found in neoadjuvantly treated patients. Follistatin
      concentration in the tumor tissue was associated with prognosis in all patients
      (P = 0.019). Tumor VEGF concentrations were correlated with histopathologic
      response (P = 0.011), with patients showing >50% remaining tumor having higher
      VEGF concentrations. The tissue Ang-2/VEGF ratio was significantly correlated
      with both clinical and histopathologic response (P = 0.029, P = 0.009).
      Additionally, the level of leptin in the tissue was associated with clinical
      response: nonresponding patients had higher leptin levels than those of
      responding patients (P = 0.032). CONCLUSIONS: Our results show the importance of
      angiogenetic factors in serum and tumor tissue in GC for prognosis and treatment
      response. Further trials in larger patient populations are warranted for a
      further evaluation of proangiogenetic factors as biomarkers in gastrointestinal
      cancer.

PMID- 25577147
TI  - SRC tyrosine kinases regulate neuronal differentiation of mouse embryonic stem
      cells via modulation of voltage-gated sodium channel activity.
AB  - Voltage-gated Na(+) channel activity is vital for the proper function of
      excitable cells and has been indicated in nervous system development. Meanwhile,
      the Src family of non-receptor tyrosine kinases (SFKs) has been implicated in the
      regulation of Na(+) channel activity. The present investigation tests the
      hypothesis that Src family kinases influence neuronal differentiation via a
      chronic regulation of Na(+) channel functionality. In cultured mouse embryonic
      stem (ES) cells undergoing neural induction and terminal neuronal
      differentiation, SFKs showed distinct stage-specific expression patterns during
      the differentiation process. ES cell-derived neuronal cells expressed multiple
      voltage-gated Na(+) channel proteins (Nav) and underwent a gradual increase in
      Na(+) channel activity. While acute inhibition of SFKs using the Src family
      inhibitor PP2 suppressed the Na(+) current, chronic inhibition of SFKs during
      early neuronal differentiation of ES cells did not change Nav expression.
      However, a long-lasting block of SFK significantly altered electrophysiological
      properties of the Na(+) channels, shown as a right shift of the current-voltage
      relationship of the Na(+) channels, and reduced the amplitude of Na(+) currents
      recorded in drug-free solutions. Immunocytochemical staining of differentiated
      cells subjected to the chronic exposure of a SFK inhibitor, or the Na(+) channel
      blocker tetrodotoxin, showed no changes in the number of NeuN-positive cells;
      however, both treatments significantly hindered neurite outgrowth. These findings
      suggest that SFKs not only modulate the Na(+) channel activation acutely, but the
      tonic activity of SFKs is also critical for normal development of functional
      Na(+) channels and neuronal differentiation or maturation of ES cells.

PMID- 25577148
TI  - Antiviral effect of sulfated Chuanmingshen violaceum polysaccharide in chickens
      infected with virulent Newcastle disease virus.
AB  - Newcastle disease virus (NDV) belonging to the Paramyxovirinae subfamily is one
      of the most devastating pathogens in poultry. Although vaccines are widely
      applied to control the infection, outbreaks of Newcastle disease (ND) repeatedly
      happen. Currently, there are no alternative control measures available for ND. In
      the present study, we found that sulfated Chuanmingshen violaceum polysaccharide
      (sCVPS) were potent inhibitors of NDV in specific pathogen free chickens infected
      with a virulent strain. With sCVPS treatment, the survival rate increased by
      almost 20% and virus titers in test organs, including brain, lung, spleen and
      thymus, were significantly decreased. The sCVPS also exhibited the ability to
      prevent viral transmission by reducing the amount of virus shed in saliva and
      feces. Higher concentrations of interferon alpha and gamma in serum were detected
      in chickens treated with sCVPS, indicating that one of the antiviral mechanisms
      may be attributed to the property of immunoenhancement. Histopathological
      examination showed that sCVPS could alleviate the tissue lesions caused by NDV
      infection. These results suggest that sCVPS are expected to be a new alternative
      control measure for NDV infection and further studies could be carried out to
      evaluate the antiviral activity of sCVPS against other paramyxoviruses. 

PMID- 25577149
TI  - An encapsidated viral protein and its role in RNA packaging by a non-enveloped
      animal RNA virus.
AB  - Alphatetraviruses are small (+) ssRNA viruses with non-enveloped, icosahedral,
      T=4 particles that assemble from 240 copies of a single capsid protein precursor.
      This study is focused on the mechanisms underlying selection and packaging of
      genomic vRNAs by Helicoverpa armigera stunt virus. We demonstrate that the viral
      protein, p17, is packaged at low levels (between 4 and 8 copies per capsid)
      raising the possibility of icosahedral asymmetry in wild-type particles. p17
      promotes packaging of vRNA2 by virus-like particles (VLPs) generated from plasmid
      expressed vRNA2. The 5' and 3' UTRs of RNA2 are not required for encapsidation.
      VLPs produced by recombinant baculoviruses package vRNA2 at detectable levels
      even in the absence of p17 and apparently excluding baculoviral transcripts. This
      suggests a role for p17 in vRNA selectivity. This is one of few examples of the
      packaging of a minor non-structural protein by (+) ssRNA animal viruses. 

PMID- 25577151
TI  - International standardization and classification of human papillomavirus types.
AB  - Established Human Papillomavirus (HPV) types, up to HPV202, belong to 49 species
      in five genera. International standardization in classification and quality
      standards for HPV type designation and detection is ensured by the International
      HPV Reference Center. The center i) receives clones of potentially novel HPV
      types, re-clones and re-sequences them. If confirmed, an HPV type number is
      assigned and posted on www.hpvcenter.se. ii) distributes reference clone samples,
      for academic research, under Material Transfer Agreements agreed with the
      originator. iii) provides preliminary checking of whether new sequences represent
      novel types iv) issues international proficiency panels for HPV genotyping. The
      rate of HPV type discovery is increasing, probably because of metagenomic
      sequencing. gamma-genus today contains 79HPV types and 27 species, surpassing ?
      and beta genera with 65 and 51HPV types, respectively. Regular issuing of
      proficiency panels based on HPV reference clones has resulted in global
      improvement of HPV genotyping services. 

PMID- 25577152
TI  - UL84-independent replication of human cytomegalovirus strains conferred by a
      single codon change in UL122.
AB  - The UL84 gene of human cytomegalovirus (HCMV) is thought to be involved in the
      initiation of viral DNA replication, and is essential for replication of strains
      AD169 and Towne. Hence, discovery that strain TB40-BAC4 is viable in the absence
      of UL84 presented an enigma requiring an explanation. Data reported here show
      that strain TR also tolerated loss of UL84, whereas strains FIX, Merlin, Ph, and
      Toledo did not. UL84-independent growth required the viral replication origin.
      The genetic locus in TB40 that controls UL84 dependence was mapped to codon 388
      of the UL122 gene, which encodes the immediate early 2 (IE2) 86kD protein.
      Introduction of this TB40-BAC4 variant (H388D) into FIX and Toledo clones
      converted these strains to UL84 independence. These results provide genetic
      evidence in virus-infected cells that supports the hypothesis that UL122
      participates in the initiation of viral DNA replication by a mechanism involving
      transcription-mediated activation of the origin. 

PMID- 25577150
TI  - Interferon-lambda4 is a cell-autonomous type III interferon associated with pre
      treatment hepatitis C virus burden.
AB  - Genetic variants surrounding the interferon-lambda3 (IFNL3) gene are strongly
      associated with clearance of hepatitis C virus (HCV). A variant (rs368234815
      TT/DeltaG) upstream of IFNL3 was recently implicated to control expression of a
      novel gene termed IFNL4. We conducted genetic analysis of rs368234815 in a
      chronic HCV patient cohort and molecular studies of IFNL4 in primary human
      hepatocytes (PHHs). Analysis of PHHs that are heterozygous at rs368234815
      revealed that the IFNL4 transcript isoform is rare, accounting for 2% of
      transcripts arising from the IFNL4 locus. Nevertheless, IFNL4 over-expression
      inhibited replication of multiple Flaviviridae and IFNL4 anti-viral potency
      required the IFNL receptor. In contrast to IFNL3, IFNL4 was inefficiently
      secreted and appeared to act in a cell-autonomous manner. Genetic analysis
      revealed associations of rs368234815 with sustained virological response and pre
      treatment viral load. The findings suggest that IFNL4 is an atypical IFNL whose
      activity may be maladaptive to clearance of HCV infection. 

PMID- 25577153
TI  - Prevalence of osteoporotic vertebral fracture in Spanish women over age 45.
AB  - The aim of this work is to study the prevalence of osteoporotic vertebral
      fractures in Spanish women over 45 years of age, based on the selection of a
      nationwide sample. An observational, cross-sectional, multicenter study was
      conducted during 2006, in all of Spain's regions. The sample analyzed was of 5000
      individuals, representative of the female population over age 45 in Spain. A
      questionnaire was used to determine which factors are most often associated with
      vertebral fractures. We also assessed whether the Prevalent Vertebral Fracture
      Index, proposed by Vogt, is useful in indicating a possible osteoporotic
      vertebral fracture. Five hundred orthopedic surgeons, from various Spanish
      regions, were trained in different aspects of the study: inclusion and exclusion
      criteria, management of the risk factor questionnaire, and implementation of the
      Vogt questionnaire. The number of fracture cases was 1549 (31.79%). 528 Women
      (34.08%) had a single vertebral fracture, and 1021 (65.92%) had multiple
      vertebral fractures. The following factors were statistically significantly
      associated with vertebral fracture: age, late menarche, early menopause, diabetes
      mellitus, hyperparathyroidism, rheumatoid arthritis, height loss, daily physical
      activity, corticosteroid therapy, personal history of osteoporotic fracture and
      previous diagnosis of osteoporosis. The differences in Vogt score according to
      age and fracture status were statistically significant. The conclusion of the
      study is that vertebral osteoporotic fracture in the female Spanish population is
      frequent. The high prevalence in the Spanish population older than 60 years is
      probably related to malnutrition in the period from 1936 to 1952. 

PMID- 25577154
TI  - First-line drugs inhibiting the renin angiotensin system versus other first-line
      antihypertensive drug classes for hypertension.
AB  - BACKGROUND: Renin-angiotensin system (RAS) inhibitors are widely prescribed for
      treatment of hypertension, especially for diabetic patients on the basis of
      postulated advantages for the reduction of diabetic nephropathy and
      cardiovascular morbidity and mortality. Despite widespread use of angiotensin
      converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for
      hypertension in both diabetic and non-diabetic patients, the efficacy and safety
      of RAS inhibitors compared to other antihypertensive drug classes remains
      unclear. OBJECTIVES: To evaluate the benefits and harms of first-line RAS
      inhibitors compared to other first-line antihypertensive drugs in patients with
      hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Group's
      Specialised Register, MEDLINE, MEDLINE In-Process, EMBASE and ClinicalTrials.gov
      for randomized controlled trials up to November 19, 2014 and the Cochrane Central
      Register of Controlled Trials (CENTRAL) up to October 19, 2014. The WHO
      International Clinical Trials Registry Platform (ICTRP) is searched for inclusion
      in the Cochrane Hypertension Group's Specialised Register. SELECTION CRITERIA: We
      included randomized, active-controlled, double-blinded studies with at least six
      months follow-up in people with primary elevated blood pressure (>=130/85 mmHg),
      which compared first-line RAS inhibitors with other first-line antihypertensive
      drug classes and reported morbidity and mortality or blood pressure outcomes.
      Patients with proven secondary hypertension were excluded. DATA COLLECTION AND
      ANALYSIS: Two authors independently selected the included trials, evaluated the
      risk of bias and entered the data for analysis. MAIN RESULTS: We included 42
      studies, involving 65,733 participants, with a mean age of 66 years. Much of the
      evidence for our key outcomes is dominated by a small number of large studies at
      a low risk of bias for most sources of bias. Imbalances in the added second-line
      antihypertensive drugs in some of the studies were important enough for us to
      downgrade the quality of the evidence.Primary outcomes were all-cause death,
      fatal and non-fatal stroke, fatal and non-fatal myocardial infarction (MI), fatal
      and non-fatal congestive heart failure (CHF) requiring hospitalization, total
      cardiovascular (CV) events (consisted of fatal and non-fatal stroke, fatal and
      non-fatal MI and fatal and non-fatal CHF requiring hospitalizations), and ESRF.
      Secondary outcomes were systolic blood pressure (SBP), diastolic blood pressure
      (DBP) and heart rate (HR).Compared with first-line calcium channel blockers
      (CCBs), we found moderate quality evidence that first-line RAS inhibitors
      decreased heart failure (HF) (35,143 participants in 5 RCTs, RR 0.83, 95% CI 0.77
      to 0.90, ARR 1.2%), and moderate quality evidence that they increased stroke
      (34,673 participants in 4 RCTs, RR 1.19, 95% CI 1.08 to 1.32, ARI 0.7%). They had
      similar effects on all-cause death (35,226 participants in 5 RCTs, RR 1.03, 95%
      CI 0.98 to 1.09; moderate quality evidence), total CV events (35,223 participants
      in 6 RCTs, RR 0.98, 95% CI 0.93 to 1.02; moderate quality evidence), total MI
      (35,043 participants in 5 RCTs, RR 1.01, 95% CI 0.93 to 1.09; moderate quality
      evidence). The results for ESRF do not exclude potentially important differences
      (19,551 participants in 4 RCTs, RR 0.88, 95% CI 0.74 to 1.05; low quality
      evidence).Compared with first-line thiazides, we found moderate quality evidence
      that first-line RAS inhibitors increased HF (24,309 participants in 1 RCT, RR
      1.19, 95% CI 1.07 to 1.31, ARI 1.0%), and increased stroke (24,309 participants
      in 1 RCT, RR 1.14, 95% CI 1.02 to 1.28, ARI 0.6%). They had similar effects on
      all-cause death (24,309 participants in 1 RCT, RR 1.00, 95% CI 0.94 to 1.07;
      moderate quality evidence), total CV events (24,379 participants in 2 RCTs, RR
      1.05, 95% CI 1.00 to 1.11; moderate quality evidence), and total MI (24,379
      participants in 2 RCTs, RR 0.93, 95% CI 0.86 to 1.01; moderate quality evidence).
      Results for ESRF do not exclude potentially important differences (24,309
      participants in 1 RCT, RR 1.10, 95% CI 0.88 to 1.37; low quality
      evidence).Compared with first-line beta-blockers, we found low quality evidence
      that first-line RAS inhibitors decreased total CV events (9239 participants in 2
      RCTs, RR 0.88, 95% CI 0.80 to 0.98, ARR 1.7%), and low quality evidence that they
      decreased stroke (9193 participants in 1 RCT, RR 0.75, 95% CI 0.63 to 0.88, ARR
      1.7% ). Our analyses do not exclude potentially important differences between
      first-line RAS inhibitors and beta-blockers on all-cause death (9193 participants
      in 1 RCT, RR 0.89, 95% CI 0.78 to 1.01; low quality evidence), HF (9193
      participants in 1 RCT, RR 0.95, 95% CI 0.76 to 1.18; low quality evidence), and
      total MI (9239 participants in 2 RCTs, RR 1.05, 95% CI 0.86 to 1.27; low quality
      evidence).Blood pressure comparisons between RAS inhibitors and other classes
      showed either no differences or small differences that did not necessarily
      correlate with the differences in the morbidity outcomes.In the protocol, we
      identified non-fatal serious adverse events (SAE) as a primary outcome. However,
      when we extracted the data from included studies, none of them reported total SAE
      in a manner that could be used in the review. Therefore, there is no information
      about SAE in the review. AUTHORS' CONCLUSIONS: We found predominantly moderate
      quality evidence that all-cause mortality is similar when first-line RAS
      inhibitors are compared to other first-line antihypertensive agents. First-line
      thiazides caused less HF and stroke than first-line RAS inhibitors. The quality
      of the evidence comparing first-line beta-blockers and first-line RAS inhibitors
      was low and the lower risk of total CV events and stroke seen with RAS inhibitors
      may change with the publication of additional trials. Compared with first-line
      CCBs, first-line RAS inhibitors reduced HF but increased stroke. The magnitude of
      the reduction in HF exceeded the increase in stroke. The small differences in
      effect on blood pressure between the different classes of drugs did not correlate
      with the differences in the primary outcomes.

PMID- 25577155
TI  - Giant congenital melanocytic nevi: selected aspects of diagnostics and treatment.
AB  - BACKGROUND: Treatment of giant melanocytic nevi (GMN) remains a multidisciplinary
      challenge. We present analysis of diagnostics, treatment, and follow- up in
      children with GMN to establish obligatory procedures in these patients.
      MATERIAL/METHODS: In 24 children with GMN, we analyzed: localization, main nevus
      diameter, satellite nevi, brain MRI, catecholamines concentrations in 24-h urine
      collection, surgery stages number, and histological examinations. The t test was
      used to compare catecholamines concentrations in patient subgroups. RESULTS: Nine
      children had "bathing trunk" nevus, 7 had main nevus on the back, 6 on head/neck,
      and 2 on neck/shoulder and neck/thorax. Brain MRI revealed neurocutaneous
      melanosis (NCM) in 7/24 children (29.2%), symptomatic in 1. Among urine
      catecholamines levels from 20 patients (33 samples), dopamine concentration was
      elevated in 28/33, noradrenaline in 15, adrenaline in 11, and vanillylmandelic
      acid in 4. In 6 NCM children, all catecholamines concentrations were higher than
      in patients without NCM (statistically insignificant). In all patients,
      histological examination of excised nevi revealed compound nevus, with
      neurofibromatic component in 15 and melanoma in 2. They remain without
      recurrence/metastases at 8- and 3-year-follow-up. There were 4/7 NCM patients
      with more than 1 follow-up MRI; in 1 a new melanin deposit was found and in 3
      there was no progression. CONCLUSIONS: Early excision with histological
      examination speeds the diagnosis of melanoma. Brain MRI is necessary to
      confirm/rule-out NCM. High urine dopamine concentration in GMN children,
      especially with NCM, is an unpublished finding that can indicate patients with
      more serious neurological disease. Treatment of GMN children should be tailored
      individually for each case with respect to all medical/psychological aspects.

PMID- 25577156
TI  - Operating characteristics of depression and anxiety disorder phenotype dimensions
      and trait neuroticism: a theoretical examination of the fear and distress
      disorders from the Netherlands study of depression and anxiety.
AB  - BACKGROUND: The receiver operating characteristics (ROC) of anhedonic depression
      and anxious arousal to detect the distress- (major depression, dysthymia,
      generalized anxiety disorder) and fear-disorder clusters (i.e. panic disorder,
      agoraphobia, social phobia) have not been reported in a large sample. METHODS: A
      sample of 2981 persons underwent structured psychiatric interview; n=652 were
      without lifetime depression and anxiety disorder history. Participants also
      completed a neuroticism scale (Revised NEO Five Factor Inventory [NEO-FFI]), and
      the 30-item short adaptation of the Mood and Anxiety Symptoms Questionnaire (MASQ
      D30) measuring anhedonic depression, anxious arousal and general distress.
      Maximal sensitivity and specificity was determined by the Youden Index and the
      area-under-the-curve (AUC) in ROC analysis. RESULTS: A total of 2624 completed
      all measures (age M=42.4 years+/-13.1, 1760 females [67.1%]), including 1060
      (40.4%) persons who met criteria for a distress-disorder, and 973 (37.1%) who met
      criteria for a fear-disorder. The general distress dimension provided the highest
      ROC values in the detection of the distress-disorders (AUC=.814,
      sensitivity=71.95%, specificity=76.34%, positive predictive value=67.33, negative
      predictive value=80.07). None of the measures provided suitable operating
      characteristics in the detection of the fear-disorders with specificity values
      <75%. LIMITATIONS: Over sampling of depression and anxiety disorders may lead to
      inflated positive- and negative predictive values. CONCLUSIONS: The MASQ-D30
      general distress dimension showed clinically suitable operating characteristics
      in the detection of distress-disorders. Neither neuroticism nor the MASQ-D30
      dimensions provided suitable operating characteristics in the detection of the
      fear-disorders.

PMID- 25577157
TI  - Association between age of disease-onset, cognitive performance and cortical
      thickness in bipolar disorders.
AB  - OBJECTIVES: Neuroimaging studies in patients with bipolar disorder (BD) have
      indicated a number of structural brain changes, including reduced cortical
      thickness. However, the effects of the course of illness, clinical and cognitive
      variables on cortical thickness in BD patients have not yet been evaluated.
      METHODS: A total of 67 individuals (32 patients with euthymic BD and 35 healthy
      and age-matched controls) underwent 3D-anatomical magnetic resonance imaging
      (MRI). Whole-brain cortical thickness and group differences were assessed using
      the Freesurfer software. Course of disease variables, clinical and cognitive
      parameters were correlated with cortical thickness measures. RESULTS: We found
      reduced cortical thickness in BD patients compared with controls in the frontal
      and temporal lobes and in several limbic areas. We also report significant
      associations between cortical thickness and age of disease-onset, speed of
      cognitive processing, executive function and depression severity in BD patients.
      CONCLUSIONS: Cortical thickness reduction across frontal and limbic areas is a
      structural correlate of affective symptom severity and cognitive impairments in
      BD as well of age of disease-onset. We may assume that frontal lobe structural
      abnormalities are present in bipolar disorder, and might lead to dysfunctional
      cognitive functioning. The causality and functional relevance beyond mere
      correlation, however, is yet to be established. Our findings encourage further
      longitudinal studies in BD patients and in healthy at-risk subjects in order to
      discern the temporal order and development of morphological changes and clinical
      symptoms.

PMID- 25577158
TI  - Impact of bariatric surgery on clinical depression. Interrupted time series study
      with matched controls.
AB  - BACKGROUND: Obesity is associated with depression. This study aimed to evaluate
      whether clinical depression is reduced after bariatric surgery (BS). METHODS:
      Obese adults who received BS procedures from 2002 to 2014 were sampled from the
      UK Clinical Practice Research Datalink. An interrupted time series design, with
      matched controls, was conducted from three years before, to a maximum of seven
      years after surgery. Controls were matched for body mass index (BMI), age, gender
      and year of procedure. Clinical depression was defined as a medical diagnosis
      recorded in year, or an antidepressant prescribed in year to a participant ever
      diagnosed with depression. Adjusted odds ratios (AOR) were estimated. RESULTS:
      There were 3045 participants (mean age 45.9; mean BMI 44.0kg/m(2)) who received
      BS, including laparoscopic gastric banding in 1297 (43%), gastric bypass in 1265
      (42%), sleeve gastrectomy in 477 (16%) and six undefined. Before surgery, 36% of
      BS participants, and 21% of controls, had clinical depression; between-group AOR,
      2.02, 95%CI 1.75-2.33, P<0.001. In the second post-operative year 32% had
      depression; AOR, compared to time without surgery, 0.83 (0.76-0.90, P<0.001). By
      the seventh year, the prevalence of depression increased to 37%; AOR 0.99 (0.76
      1.29, P=0.959). LIMITATIONS: Despite matching there were differences in
      depression between BS and control patients, representing the highly selective
      nature of BS. CONCLUSIONS: Depression is frequent among individuals selected to
      undergo bariatric surgery. Bariatric surgery may be associated with a modest
      reduction in clinical depression over the initial post-operative years but this
      is not maintained.

PMID- 25577159
TI  - Specificity of abnormal brain volume in major depressive disorder: a comparison
      with borderline personality disorder.
AB  - BACKGROUND: Abnormal brain volume has been frequently demonstrated in major
      depressive disorder (MDD). It is unclear if these findings are specific for MDD
      since aberrant brain structure is also present in disorders with depressive
      comorbidity and affective dysregulation, such as borderline personality disorder
      (BPD). In this transdiagnostic study, we aimed to investigate if regional brain
      volume loss differentiates between MDD and BPD. Further, we tested for
      associations between brain volume and clinical variables within and between
      diagnostic groups. METHODS: 22 Females with a DSM-IV diagnosis of MDD, 17 females
      with a DSM-IV diagnosis of BPD and without comorbid posttraumatic stress
      disorder, and 22 age-matched female healthy controls (HC) were investigated using
      magnetic resonance imaging. High-resolution structural data were analyzed using
      voxel-based morphometry. RESULTS: A significant (p<0.05, cluster-corrected)
      volume decrease of the anterior cingulate cortex (ACC) was found in MDD compared
      to HC, as opposed to volume decreases of the amygdala in BPD compared to both HC
      and MDD. Sensitivity and specificity of regional gray matter volume for a
      diagnosis of MDD were modest to fair. Amygdala volume was related to depressive
      symptoms across the entire patient sample. LIMITATIONS: Potential limitations of
      this study include the modest sample size and the heterogeneous psychotropic drug
      treatment. CONCLUSIONS: ACC volume reduction is more pronounced in MDD with an
      intermediate degree of volume loss in BPD compared to HC. In contrast, amygdala
      volume loss is more pronounced in BPD compared to MDD, yet amygdala volume is
      associated with affective symptom expression in both disorders.

PMID- 25577160
TI  - Exploring the links between the phenomenology of creativity and bipolar disorder.
AB  - BACKGROUND: The links between bipolar disorder (BD) and creativity have
      historically attracted academic and public interest. Previous research highlights
      common characteristics of people considered to be highly creative, and those
      diagnosed with BD, including extraversion, impulsivity, divergent thinking and
      high motivation (Ma, 2009). METHOD: In the first phenomenological study focussing
      on the links between creativity and extreme mood, an Interpretative
      Phenomenological Analysis (IPA) approach was used to collect and analyse in-depth
      interview data from seven people diagnosed with BD in the UK. RESULTS: Four key
      themes were constructed to reflect and convey the collective accounts: 1. High
      mood leads to an expanding mind; 2. Full steam ahead; 3. A reciprocal
      relationship between mood and creativity 4. Reframing bipolar experiences through
      creative activity. LIMITATIONS: Participants were a small sample of people who
      were identified as having BD on the basis of a clinical diagnosis and Mood
      Disorders screening Questionnaire (MDQ), and who defined themselves as creative
      without further corroboration. CONCLUSIONS: Among this sample, creativity was
      recognised as a valued aspect of BD. Clinical services may usefully draw on
      creative resources to aid assessment and formulation, and even utilise the
      effects of creativity on the management of mood. Research demonstrates a high
      prevalence of non-adherence to medication among persons with BD and this
      ambivalence might be better understood when the links between extreme mood and
      creativity are considered.

PMID- 25577161
TI  - Genomewide admixture study in Mexican Mestizos with multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a complex immune-mediated disease. It has
      been suggested that genetic factors could explain differences in the prevalence
      among ethnic groups. To know whether genetic ancestry is a potential risk factor
      for MS in Mexican patients and to identify candidate genes for the susceptibility
      to the disease we conducted an initial trial of genome-wide analysis. METHODS: 29
      patients with diagnosis of definitive MS and 132 unrelated healthy controls were
      genotyped using the Affymetrix human 6.0 array. After QC procedures, ancestry
      determination and a preliminary case-control association study were performed.
      RESULTS: We identified significant differences in the European ancestry
      proportion between MS cases and controls (33.1 vs. 25.56, respectively;
      p=0.0045). Imputation analysis in the MHC region on chromosome 6 showed a signal
      with a significant level (p<0.00005) on the HLA-DRB region. Additionally, a
      preliminary association analysis highlighted the ASF1B as novel candidate gene
      participating in MS. CONCLUSION: Our data suggest that European ancestry is a
      risk factor to develop MS in Mexican Mestizo population. Conversely, indigenous
      ancestry of Asian origin seems to confer protection. Further studies with more MS
      cases are needed to confirm these findings.

PMID- 25577162
TI  - Hegemann's disease and fishtail deformity: aetiopathogenesis, radiographic
      appearance and clinical outcome.
AB  - PURPOSE: A systematic review regarding clinical studies on Hegemann's disease and
      fishtail deformity was performed with the aims to: (1) formulate the most up-to
      date theory on aetiology in order to better define these conditions, (2)
      summarise the most frequent radiographic descriptions on radiographs and (3) give
      an overview of different treatment options. METHODS: A systematic review of
      studies to date on Hegemann's disease and fishtail deformity was performed.
      Studies were eligible if: (1) the article provides a description of Hegemann's
      disease or fishtail deformity, (2) original data of at least one patient was
      available, (3) the article was written in English, German or Dutch and (4) a full
      manuscript was available. Animal studies, reviews and expert opinions were not
      included. RESULTS: We included a total of 22 articles: seven regarding Hegemann's
      disease including eight patients and 15 regarding fishtail deformity including 58
      patients. CONCLUSIONS: Fishtail deformity and Hegemann's disease seem to be a
      spectrum of vascular disorders of the distal humerus, varying from a benign mild
      vascular disorder to a complete avascular necrosis after fractures. Additional
      imaging is advised to confirm the presence of a fishtail deformity, intra
      articular loose bodies and signs of osteoarthritis to decide if, and what,
      operative treatment is needed. As long as no clear aetiology for both diseases
      exist and the clinical symptoms and radiographic appearance are difficult to
      distinguish, both entities should preferably be named as 'vascular disturbance of
      the trochlear growth plate' to overcome confusing definitions and discussions.

PMID- 25577164
TI  - Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial.
AB  - BACKGROUND: N-methyl-D-aspartate receptor antagonists, such as ketamine, have
      rapid antidepressant effects in patients with treatment-resistant depression
      (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and
      N-methyl-D-aspartate receptor antagonist, may also be a rapidly acting treatment
      for TRD. METHODS: In this blinded, placebo-controlled crossover trial, 20
      patients with TRD were randomly assigned to 1-hour inhalation of 50% nitrous
      oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). The primary
      endpoint was the change on the 21-item Hamilton Depression Rating Scale (HDRS-21)
      24 hours after treatment. RESULTS: Mean duration of nitrous oxide treatment was
      55.6 +/- 2.5 (SD) min at a median inspiratory concentration of 44% (interquartile
      range, 37%-45%). In two patients, nitrous oxide treatment was briefly
      interrupted, and the treatment was discontinued in three patients. Depressive
      symptoms improved significantly at 2 hours and 24 hours after receiving nitrous
      oxide compared with placebo (mean HDRS-21 difference at 2 hours, -4.8 points, 95%
      confidence interval [CI], -1.8 to -7.8 points, p = .002; at 24 hours, -5.5
      points, 95% CI, -2.5 to -8.5 points, p < .001; comparison between nitrous oxide
      and placebo, p < .001). Four patients (20%) had treatment response (reduction
      >=50% on HDRS-21) and three patients (15%) had a full remission (HDRS-21 <= 7
      points) after nitrous oxide compared with one patient (5%) and none after placebo
      (odds ratio for response, 4.0, 95% CI, .45-35.79; OR for remission, 3.0, 95% CI,
      .31-28.8). No serious adverse events occurred; all adverse events were brief and
      of mild to moderate severity. CONCLUSIONS: This proof-of-concept trial
      demonstrated that nitrous oxide has rapid and marked antidepressant effects in
      patients with TRD.

PMID- 25577165
TI  - Molecular characterization of 3'UTRs of J subgroup avian leukosis virus in
      passerine birds in China.
AB  - To assess the status of avian leukosis virus subgroup J (ALV-J) infection in
      passerine birds in China, 365 passerine birds collected from northeast China from
      2011 to 2013 were tested, and two ALV-J strains were isolated from yellow-browed
      warbler and marsh tit. The 3'untranslated regions (3'UTRs) of the two strains
      were amplified, cloned, and sequenced, with the results showing that the 3'UTRs
      of the two strains contained multiple mutations and deletions, which are similar
      to viral strains isolated from Chinese layer chickens. These results demonstrate
      the presence of ALV-J in passerine birds and reveal the molecular characteristics
      of the 3'UTRs of ALV-J from passerine birds.

PMID- 25577163
TI  - An overview of the metabolic functions of osteocalcin.
AB  - A recent unexpected development of bone biology is that bone is an endocrine
      organ contributing to the regulation of a number of physiological processes. One
      of the functions regulated by bone through osteocalcin, an osteoblast specific
      hormone, is glucose homeostasis. In this overview, we explain the rationale why
      we hypothesized that there should be a coordinated endocrine regulation between
      bone mass and energy metabolism. We then review the experiments that identified
      the endocrine function of osteocalcin and the cell biology events that allow
      osteocalcin to become a hormone. We also demonstrate the importance of this
      regulation to understand whole-body glucose homeostasis in the physiological
      state and in pathological conditions. Lastly we discuss the epidemiological and
      genetic evidence demonstrating that this function of osteocalcin is conserved in
      humans. 

PMID- 25577166
TI  - Complete genome sequence of two rabbit hemorrhagic disease virus variant b
      isolates detected on the Iberian Peninsula.
AB  - We report the complete genome sequences of two isolates (RHDV-N11 and CBVal16) of
      variant rabbit hemorrhagic disease virus (RHDVb). Isolate N11 was detected in
      young domestic animals during a rabbit hemorrhagic disease (RHD) outbreak that
      occurred in 2011 on a rabbit farm in Navarra, Spain, while CBVal16 was isolated
      from a wild rabbit found dead in Valpacos, Northern Portugal, a year later. The
      viral sequences reported show 84.8-85.1 % and 78.3-78.5 % identity to RHDVAst/89
      and RCV-A1 MIC-07, representative members of the pathogenic genogroup 1 RHDV and
      apathogenic rabbit calicivirus, respectively. In comparison with other RHDV
      isolates belonging to the previously known genogroups 1-6, RHDVb shows marked
      phenotypic differences, as it causes disease preferentially in young rabbits
      under 40 days of age and shows modified red blood cell agglutination profiles as
      well as antigenic differences that allow this variant to escape protection by the
      currently available vaccines.

PMID- 25577167
TI  - A new nepovirus identified in mulberry (Morus alba L.) in China.
AB  - An isometric virus was identified in mulberry leaves showing symptoms of mulberry
      mosaic leaf roll (MMLR) disease. Its genome consists of two (+)ssRNAs. RNA1 and
      RNA2 have 7183 and 3742 nucleotides, excluding the 3'-terminal poly(A) tail.
      Based on phylogenetic analysis of the RNA1-encoded polyprotein and CP amino acid
      sequences, the properties of the the 3'-UTR of RNA1 and RNA2, and <75 % identity
      in the CP amino acid sequence, this virus is proposed to be a new member of the
      genus Nepovirus, subgroup A. Since a causal relationship between this virus and
      MMLR has not been established, it is tentatively referred to as MMLR-associated
      virus.

PMID- 25577168
TI  - Identification and sequence determination of a novel double-stranded RNA
      mycovirus from the entomopathogenic fungus Beauveria bassiana.
AB  - An isolate of the entomopathogenic fungus Beauveria bassiana was found to contain
      five double-stranded (ds) RNA elements ranging from 1.5 to more than 3 kbp. The
      complete sequence of the largest dsRNA element is described here. Analysis of the
      RdRp nucleotide sequence reveals its similarity to unclassified dsRNA elements,
      such as Alternaria longipes dsRNA virus 1, and its distant relationship to the
      RNA-dependent RNA polymerases of members of the family Partitiviridae.

PMID- 25577169
TI  - [Comparison between closure and absence of closure after removal of fully
      impacted mandibular third molar: a prospective randomized study].
AB  - We prospectively and randomly assessed the absence of surgical wound closure on
      the patient's postoperative outcome when removing impacted mandibular third
      molars. MATERIAL AND METHOD: Patients were randomized in 2 groups: the "open
      group" (O) and the "closed group" (C). We considered the postoperative
      perimandibular edema, postoperative pain, and limitation of mouth opening at
      preoperative time, Day2, and Day7. The same physician performed all preoperative
      (D0) and postoperative measures (D2, D7). RESULTS: Fifty-four patients (27 female
      and 27 male patients) were included in the study. Ninety-nine cases of impacted
      mandibular third molars were studied. The statistical analysis revealed a
      significantly more important postoperative edema in Group C at D2 (P<0.0001) and
      at D7 (P<0.0001). Postoperative mandibular pain was significantly greater in
      Group C at D2 (P<0.05) but not at D7 (P>0.05). The decrease of mouth opening was
      significantly more important in Group C at D2 and at D7 (P<0.05). DISCUSSION: Our
      prospective randomized study data suggests a significant improvement of
      postoperative outcome when the mucoperiosteal flap was not sutured after removal
      of impacted third molars.

PMID- 25577170
TI  - Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating
      PI3K, ERK and Free Radical Scavenging.
AB  - Although statins, or hydroxymethylglutaryl coenzyme A (HMG-Co A) reductase
      inhibitors, are generally used to decrease levels of circulating cholesterol,
      they have also been reported to have neuroprotective effects through various
      mechanisms. However, recent results have indicated that they may be harmful in
      patients with amyotrophic lateral sclerosis (ALS). In this study, we investigate
      whether atorvastatin protects motor neuron-like cells (NSC-34D) from oxidative
      stress. To evaluate the effects of atorvastatin or hydrogen peroxide or both on
      NSC-34D cells, the cells were treated with various combinations of these agents.
      To evaluate the viability of the cells, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assays and trypan blue staining were performed.
      Levels of free radicals and intracellular signaling proteins were evaluated using
      the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and
      Western blotting, respectively. Atorvastatin protected NSC-34D cells against
      oxidative stress in a concentration-dependent manner. This neuroprotective effect
      of atorvastatin was blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K)
      inhibitor and by FR180204, a selective extracellular signal-related kinase (ERK)
      inhibitor. Atorvastatin treatment increased the expression levels of
      p85alphaPI3K, phosphorylated Akt, phosphorylated glycogen synthase kinase-3beta,
      phosphorylated ERK, and Bcl-2, which are proteins related to survival.
      Furthermore, atorvastatin decreased the levels of cytosolic cytochrome C, Bax,
      cleaved caspase-9, and cleaved caspase-3, which are associated with death in
      oxidative stress-injured NSC-34D cells. We conclude that atorvastatin has a
      protective effect against oxidative stress in motor neurons by activating the
      PI3K and ERK pathways as well as by scavenging free radicals. These findings
      indicate that statins could help protect motor neurons from oxidative stress.

PMID- 25577171
TI  - Propofol Administration During Early Postnatal Life Suppresses Hippocampal
      Neurogenesis.
AB  - Propofol is currently one of the most widely used intravenous anesthetics and has
      been indicated to induce cognitive dysfunction in adults. Here, we investigated
      the effects of propofol exposure during early postnatal life on hippocampal
      neurogenesis. Propofol (30 or 60 mg/kg) was administered to mice on either
      postnatal day (P) 7 or P7-P9; cell proliferation and neurogenesis in the dentate
      gyrus (DG) were evaluated on P8 or P17. It showed that exposure to propofol on P7
      decreased hippocampal cell proliferation as indicated by BrdU and Sox2
      immunostaining at P8 in propofol treatment at the dosage of 60 mg/kg but not at
      the dosage of 30 mg/kg. Western blots revealed propofol treatment decreased Akt
      or extracellular signal-related kinase (ERK) 1/2 phosphorylation in the
      hippocampus at P8. Propofol treatment on P7 to P9 reduced the numbers of newly
      formed neurons in the DG at P17, which was accompanied by delay of granule neuron
      maturation and decreased the density of dendritic spines, particularly the
      mushroom-shaped mature spines. Furthermore, the in vitro findings indicated
      propofol suppressed cell proliferation and cell mitosis and activated apoptosis
      of C17.2 neural stem cell line in a dose-dependent manner. These findings suggest
      that propofol impairs cell proliferation and inhibits neurogenesis in the
      immature mouse brain and thus is possibly involved in the cognitive dysfunction
      induced by propofol anesthesia.

PMID- 25577173
TI  - Erratum to: Elevated cerebral cortical CD24 levels in patients and mice with
      traumatic brain injury: a potential negative role in nuclear factor kappa
      B/inflammatory factor pathway.

PMID- 25577174
TI  - Single nucleotide polymorphisms in immune response genes in acute Q fever cases
      with differences in self-reported symptoms.
AB  - Genes involved in human immune response are well recognized to influence the
      clinical course of infection. The association of host genetics with
      susceptibility to and severity of clinical symptoms in acute Q fever was
      investigated. Single nucleotide polymorphisms (SNPs) in the IFNG
      (rs2430561/rs1861493), STAT1 (rs1914408), and VDR (rs2228570) genes were
      determined in 85 patients from the 2007 Dutch acute Q fever outbreak, and a
      symptom score was calculated. IFNG rs1861493 showed a significant association
      with the symptom score; IFNG rs2430561 showed a similar trend. These SNPs were
      then used to reproduce results in a 2009 outbreak population (n = 123). The
      median symptom score differed significantly in both populations: 2 versus 7. The
      significant association of IFNG rs1861493 with symptom score in the first
      population was not reproduced in the second population. We hypothesize that
      individuals in the second outbreak were exposed to a higher Coxiella burnetii
      dose compared to the first, which overruled the protection conferred by the A
      allele of IFNG rs1861493 in the first population. 

PMID- 25577175
TI  - Economic evaluation of a preemptive treatment strategy for invasive fungal
      infection in neutropenic patients with hematological diseases.
AB  - We compared the expected medical costs of empirical and preemptive treatment
      strategies for invasive fungal infection in neutropenic patients with
      hematological diseases. Based on the results of two clinical trials with
      different backgrounds reported by Oshima et al. [J Antimicrob Chemother 60(2):350
      355; Oshima study] and Cordonnier et al. [Clin Infect Dis 48(8):1042-1051;
      PREVERT study], we developed a decision tree model that represented the outcomes
      of empirical and preemptive treatment strategies, and estimated the expected
      medical costs of medications and examinations in the two strategies. We assumed
      that micafungin was started in the empirical group at 5 days after fever had
      developed, while voriconazole was started in the preemptive group only when
      certain criteria, such as positive test results of imaging studies and/or serum
      markers, were fulfilled. When we used an incidence of positive test results of
      6.7 % based on the Oshima study, the expected medical costs of the empirical and
      preemptive groups were 288,198 and 150,280 yen, respectively. Even in the case of
      the PREVERT study, in which the incidence of positive test results was 32.9 %,
      the expected medical costs in the empirical and preemptive groups were 291,871
      and 284,944 yen, respectively. A sensitivity analysis indicated that the expected
      medical costs in the preemptive group would exceed those in the empirical group
      when the incidence of positive test results in the former was over 34.4 %. These
      results suggest that a preemptive treatment strategy can be expected to reduce
      medical costs compared with empirical therapy in most clinical settings. 

PMID- 25577172
TI  - ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia.
AB  - An acute bout of exercise can exacerbate pain, hindering participation in regular
      exercise and daily activities. The mechanisms underlying pain in response to
      acute exercise are poorly understood. We hypothesized that proton accumulation
      during muscle fatigue activates acid-sensing ion channel 3 (ASIC3) on muscle
      nociceptors to produce hyperalgesia. We investigated the role of ASIC3 using
      genetic and pharmacological approaches in a model of fatigue-enhanced
      hyperalgesia. This model uses two injections of pH 5.0 saline into muscle in
      combination with an electrically induced fatigue of the same muscle just prior to
      the second injection of acid to induce mechanical hyperalgesia. We show a
      significant decrease in muscle force and decrease in muscle pH after 6 min of
      electrical stimulation. Genetic deletion of ASIC3 using knockout mice and
      pharmacological blockade of ASIC3 with APETx2 in muscle prevents the fatigue
      enhanced hyperalgesia. However, ASIC3(-/-) mice and APETx2 have no effect on the
      fatigue response. Genetic deletion of ASIC3 in primary afferents innervating
      muscle using an HSV-1 expressing microRNA (miRNA) to ASIC3 surprisingly had no
      effect on the development of the hyperalgesia. Muscle fatigue increased the
      number of macrophages in muscle, and removal of macrophages from muscle with
      clodronate liposomes prevented the development of fatigue-enhanced hyperalgesia.
      Thus, these data suggest that fatigue reduces pH in muscle that subsequently
      activates ASIC3 on macrophages to enhance hyperalgesia to muscle insult.

PMID- 25577176
TI  - Intravenous immunoglobulin for chronic residual peripheral neuropathy in
      eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a
      multicenter, double-blind trial.
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg
      Strauss syndrome, frequently affects the peripheral nervous system. We conducted
      a multicenter, double-blind, three-arm treatment period, randomized, pre-post
      trial to assess the efficacy of intravenous immunoglobulin (IVIg) administration
      for residual peripheral neuropathy in patients with EGPA that is in remission,
      indicated by laboratory indices. Twenty-three patients were randomly assigned
      into three groups, in which the timing of IVIg and placebo administration was
      different. Each group received one course of intervention and two courses of
      placebo at 2-week intervals. Treatment effects were assessed every 2 weeks for 8
      weeks. The primary outcome measure, the amount of change in the manual muscle
      testing sum score 2 weeks after IVIg administration, significantly increased (p =
      0.002). The results over time suggested that this effect continued until the last
      assessment was done 8 weeks later. The number of muscles with manual muscle
      testing scores of three or less (p = 0.004) and the neuropathic pain scores
      represented by the visual analogue scale (p = 0.005) also improved significantly
      2 weeks after IVIg administration. This study indicates that IVIg treatment for
      EGPA patients with residual peripheral neuropathy should be considered even when
      laboratory indices suggest remission of the disease.

PMID- 25577177
TI  - Decreased interhemispheric functional connectivity in subtypes of Parkinson's
      disease.
AB  - Parkinson's disease (PD) can be classified into tremor-dominant (TD) subtype and
      akinetic-rigid (AR) subtype, which exhibit different clinical courses and
      prognoses. However, the neural mechanisms underlying different subtypes of PD are
      not well understood. Using voxel-mirrored homotopic connectivity (VMHC), we
      examined the homotopic resting-state functional connectivity patterns in akinetic
      rigid PD (AR-PD) and tremor-dominant PD (TD-PD) to study the neural basis for
      these disparate manifestations of PD. Twenty-one TD-PD patients, 29 AR-PD
      patients and 26 normal control subjects participated in this study. Resting-state
      fMRI data were analyzed using VMHC. Correlations between VMHC values and each
      clinical characteristic were also calculated. Compared with normal control
      subjects and subjects with AR-PD, subjects with TD-PD exhibited significantly
      lower VMHC values in the posterior lobe of the cerebellum. Moreover, tremor
      scores and VMHC values for the cerebellum were found to be significantly
      negatively correlated in TD-PD patients. By contrast, subjects with AR-PD
      exhibited lower VMHC values in the precentral gyrus compared with normal control
      subjects. These findings suggest that functional coordination between homotopic
      brain regions is impaired in AR-PD and TD-PD patients. This study provides
      evidence of both cerebellum-related connectivity deficits in TD-PD. The finding
      that VMHC values and tremor scores were significantly correlated suggests that
      VMHC measurements may be of potential clinical relevance in TD-PD. 

PMID- 25577178
TI  - Effects of parent management training programs on disruptive behavior for
      children with a developmental disability: a meta-analysis.
AB  - This meta-analysis determined the effects of parent management training (PMT) on
      disruptive behaviors in children with a developmental disability. Parent
      management training programs, based on behavioral theories of psychology, are
      commonly used in addressing disruptive behavior in children. Eleven studies met
      inclusion criteria with a total of 540 participants, with 275 in experimental
      groups and 265 in control groups. The effect of PMT on the disruptive behavior in
      children with a developmental disability was significant (g=0.39). The moderator
      effects of type of PMT, delivery type and setting, and administrator level of
      education were also significant. The moderator effects of child age, and session
      number and duration were not significant in this meta-analysis. 

PMID- 25577179
TI  - Development of a tool to describe overall health, social independence and
      activity limitation of adolescents and young adults with disability.
AB  - There is a need for research that focuses on the correlation between self
      perceived quality of life (QoL) and the health outcomes of adolescents with
      disability transitioning to adulthood. To better understand the transition
      experience of adolescents and young adults with disability, we developed a
      questionnaire to assess the impact of disability on QoL. We recruited 174
      participants who were 15-24 years old and diagnosed with Fragile X syndrome
      (FXS), spina bifida (SB) or muscular dystrophy (MD) and conducted an exploratory
      factor analysis to identify factors that characterize QoL. Five factors emerged:
      emotional health, physical health, independence, activity limitation, and
      community participation. To validate the tool, we linked medical claims and other
      administrative data records and examined the association of the factor scores
      with health care utilization and found the questionnaire can be utilized among
      diverse groups of young people with disability. 

PMID- 25577180
TI  - Perinatal stroke causes abnormal trajectory and laterality in reaching during
      early infancy.
AB  - The developmental progression of reaching and early signs of upper extremity
      neglect is common concern for infants at risk for hemiparesis and cerebral palsy.
      We investigated the emergence of reaching and laterality in infants at risk for
      hemiplegic cerebral palsy. Eight infants with perinatal stroke (PS) and thirteen
      infants with typical development (TD) were assessed bimonthly from 2 to 7 months
      of age for 10 visits per infant. Reaching number and hand-toy contact duration
      were measured. Infants with PS demonstrated a linear trajectory of reaching
      behaviors with asymmetrical upper extremity performance. Infants with TD
      demonstrated a linear and quadratic trajectory of reaching behaviors and
      symmetrical upper extremity performance over the same age range. These results
      suggest that infants with PS have delay reaching and early signs of neglect not
      currently accounted for in clinical practice. 

PMID- 25577181
TI  - The preliminary analysis of the reliability and validity of the Chinese Edition
      of the CSBS DP.
AB  - This study marked a preliminary attempt to standardize the Chinese Edition of the
      Communication and Symbolic Behavior Scales Developmental Profile (Wetherby &
      Prizant, 2002; CSBS DP) to assist in the early identification of young children
      with special needs in Taiwan. The study was conducted among 171 infants and
      toddlers aged 1-2. It also included a follow-up study one year after the initial
      test. Three domestically developed standardized child development inventories
      were used to measure the concurrent validity and predictive validity. The Chinese
      Edition of the CSBS DP demonstrated overall good test-retest and inter-rater
      reliability. It also showed good concurrent and predictive validity. The current
      study yields preliminary evidence that the Chinese Edition of the CSBS DP could
      be a valuable assessment tool worthy of wider distribution. Future research
      should employ random sampling to establish a true national norm. Additionally,
      the follow-up study needs to include atypical groups and to expand to children
      aged 6-12 months to strengthen the applicability of the instrument in Taiwan. 

PMID- 25577182
TI  - Substance use disorders in individuals with mild to borderline intellectual
      disability: current status and future directions.
AB  - Knowledge regarding substance use (SU) and substance use disorder (SUD) in
      individuals with mild to borderline intellectual disabilities (ID) has increased
      over the last decade, but is still limited. Data on prevalence and risk factors
      are fragmented, and instruments for screening and assessment and effective
      treatment interventions are scarce. Also, scientific developments in other fields
      are insufficiently incorporated in the care for individuals with ID and SUD. In
      this selective and critical review, we provide an overview of the current status
      of SU(D) in ID and explore insights on the conceptualisation of SUD from other
      fields such as addiction medicine and general psychiatry. SU(D) turns out to be a
      chronic, multifaceted brain disease that is intertwined with other physical,
      psychiatric and social problems. These insights have implications for practices,
      policies and future research with regard to the prevalence, screening, assessment
      and treatment of SUD. We will therefore conclude with recommendations for future
      research and policy and practice, which may provide a step forward in the care
      for individuals with ID and SUD. 

PMID- 25577183
TI  - Authors' reply.

PMID- 25577184
TI  - Diastolic dysfunction and cerebrovascular redistribution precede overt recipient
      twin cardiomyopathy in early-stage twin-twin transfusion syndrome.
AB  - BACKGROUND: Indications for intervention in early-stage (Quintero I and II) twin
      twin transfusion syndrome (TTTS) are not standardized. Fetal echocardiography can
      be used to guide the management of early-stage patients. The aim of this study
      was to identify early cardiovascular findings that may precede progression to
      overt recipient twin (RT) cardiomyopathy in early-stage TTTS. METHODS: This was a
      retrospective review of pregnancies evaluated from 2004 to 2010. Subjects were
      included when initial evaluation identified Quintero I or II TTTS without
      evidence of "overt" RT cardiomyopathy, defined on the basis of atrioventricular
      valve regurgitation, ventricular hypertrophy, and abnormal Doppler myocardial
      performance indices. Patients elected management with observation or
      amnioreduction. Pregnancies were grouped by whether the RT developed overt
      cardiomyopathy. Initial values, including myocardial performance index, diastolic
      filling time corrected for heart rate (Doppler inflow duration/cardiac cycle
      length), pulsatility indices of the ductus venosus, umbilical artery, and middle
      cerebral artery, and cerebroplacental ratio (middle cerebral artery PI/umbilical
      artery PI), were compared. RESULTS: Of 174 pregnancies evaluated with early-stage
      TTTS, 45 (26%) did not show evidence of RT cardiomyopathy. Follow-up
      echocardiography identified cardiomyopathy in 20 of 45 RTs (44%). Those RTs with
      subsequent cardiomyopathy had shorter diastolic filling times corrected for heart
      rate, higher ductus venosus PIs, lower middle cerebral artery PIs, and lower
      cerebroplacental ratios on initial echocardiography. CONCLUSION: Diastolic
      dysfunction and cerebroplacental redistribution precede findings of overt
      cardiomyopathy in RTs with early-stage TTTS. Assessment of these parameters may
      allow earlier identification of RTs with cardiac disease and help guide
      management. Prospective studies are needed to assess the role of echocardiography
      in patient selection for the treatment of early-stage TTTS.

PMID- 25577185
TI  - Global longitudinal strain and global circumferential strain by speckle-tracking
      echocardiography and feature-tracking cardiac magnetic resonance imaging:
      comparison with left ventricular ejection fraction.
AB  - BACKGROUND: Left ventricular (LV) ejection fraction (EF) is a routine clinical
      standard to assess cardiac function. Global longitudinal strain (GLS) and global
      circumferential strain (GCS) have emerged as important LV functional measures.
      The objective of this study was to determine the relationships of GLS and GCS by
      speckle-tracking echocardiography and featuring-tracking cardiac magnetic
      resonance (CMR) to CMR EF as a standard of reference in the same patients.
      METHODS: A total of 73 consecutive patients aged 55 +/- 15 years clinically
      referred for both CMR and echocardiography (EF range, 8%-78%) were studied.
      Routine steady-state free precession CMR images were prospectively analyzed
      offline using feature-tracking software for LV GLS, GCS, volumes, and EF. GLS was
      averaged from three standard longitudinal views and GCS from the mid-LV short
      axis plane. Echocardiographic speckle-tracking was used from the similar imaging
      planes for GLS, GCS, LV volumes, and EF. RESULTS: Feature-tracking CMR strain was
      closely correlated with speckle-tracking strain in the same patients: GLS, r = 
      0.87; GCS, r = -0.92 (P < .0001). End-diastolic and end-systolic volumes and EF
      by feature-tracking CMR were significantly correlated with standard manual
      tracing of multiple CMR short-axis images (r = 0.97, r = 0.98, and r = 0.97, P <
      .0001 for all). GLS and GCS by echocardiography and CMR feature-tracking were
      closely correlated with standard CMR EF: r = -0.85 and r = -0.95, respectively (P
      < .001). Global strain measures (in absolute values) were correlated with EF
      using the formula EF = 3(GLS) + 8% or EF = 2.5(GCS) + 8%. CONCLUSIONS: GLS and
      GCS by feature-tracking CMR analysis was a rapid means to obtain myocardial
      strain similar to speckle-tracking echocardiography. GLS and GCS were closely
      correlated with CMR EF in this patient series and may play a role in the clinical
      assessment of LV function.

PMID- 25577186
TI  - Changes in body mass and metabolic profiles in patients with first-episode
      schizophrenia treated for 12 months with a first-generation antipsychotic.
AB  - OBJECTIVES: To assess changes in body mass and metabolic profiles in patients
      with first-episode schizophrenia receiving standardised, assured treatment and to
      identify predictors and moderators of the effects. METHODS: We investigated the
      changes in body mass, fasting blood glucose and lipids in 107 largely
      antipsychotic naive, first-episode schizophrenia patients who were treated
      according to a standard algorithm with long-acting injectable flupenthixol
      decanoate over 12 months. RESULTS: Eighty-three (78%) participants completed the
      12 months of treatment, and 104 (97%) received 100% of the prescribed injections
      during their participation. There were significant increases in BMI (P<.0001),
      waist circumference (P=0.0006) and triglycerides (P=0.03) and decrease in HDL
      (P=0.005), while systolic (P=0.7) and diastolic blood pressure (P=0.8), LDL
      (P=0.1), cholesterol (P=0.3), and glucose (P=0.9) values did not change over
      time. The triglyceride: HDL ratio increased by 91%. Change in BMI was only
      correlated with change in triglycerides (P=.008). The only significant predictor
      of BMI increase was non-substance abuse (P=.002). CONCLUSIONS: The risks of
      weight gain and metabolic syndrome associated with antipsychotic treatment in
      first-episode schizophrenia are not restricted to second generation
      antipsychotics. This is a global problem, and developing communities may be
      particularly susceptible.

PMID- 25577188
TI  - Health and vitality assessment of two common pine species in the context of
      climate change in southern Europe.
AB  - The Mediterranean Basin is expected to be more strongly affected by ongoing
      climate change than most other regions of the earth. The South-eastern France can
      be considered as case study for assessing global change impacts on forests. Based
      on non-parametric statistical tests, the climatic parameters (temperature,
      relative humidity, rainfall, global radiation) and forest-response indicators
      (crown defoliation, discoloration and visible foliar ozone injury) of two pine
      species (Pinus halepensis and Pinus cembra) were analyzed. In the last 20 years,
      the trend analyses reveal a clear hotter and drier climate along the coastline
      and slightly rainier inland. In the current climate change context, a reduction
      in ground-level ozone (O3) was found at remote sites and the visible foliar O3
      injury decreased while deterioration of the crown conditions was observed likely
      due to a drier and warmer climate. Clearly, if such climatic and ecological
      changes are now being detected when the climate, in South-eastern France, has
      warmed in the last 20 years (+0.46-1.08 degrees C), it can be expected that many
      more impacts on tree species will occur in response to predicted temperature
      changes by 2100 (+1.95-4.59 degrees C). Climate change is projected to reduce the
      benefits of O3 precursor emissions controls leading to a higher O3 uptake.
      However, the drier and warmer climate should induce a soil drought leading to a
      lower O3 uptake. These two effects, acting together in an opposite way, could
      mitigate the harmful impacts of O3 on forests. The development of coordinated
      emission abatement strategies is useful to reduce both climate change and O3
      pollution. Climate change will create additional challenges for forest management
      with substantial socio-economic and biological diversity impacts. However, the
      development of future sustainable and adaptive forest management strategies has
      the potential to reduce the vulnerability of forest species to climate change. 

PMID- 25577187
TI  - Assessment of mercury exposure among small-scale gold miners using mercury stable
      isotopes.
AB  - Total mercury (Hg) concentrations in hair and urine are often used as biomarkers
      of exposure to fish-derived methylmercury (MeHg) and gaseous elemental Hg,
      respectively. We used Hg stable isotopes to assess the validity of these
      biomarkers among small-scale gold mining populations in Ghana and Indonesia.
      Urine from Ghanaian miners displayed similar Delta(199)Hg values to Hg derived
      from ore deposits (mean urine Delta(199)Hg=0.010/00, n=6). This suggests that
      urine total Hg concentrations accurately reflect exposure to inorganic Hg among
      this population. Hair samples from Ghanaian miners displayed low positive
      Delta(199)Hg values (0.23-0.550/00, n=6) and low percentages of total Hg as MeHg
      (7.6-29%, n=7). These data suggest that the majority of the Hg in these miners'
      hair samples is exogenously adsorbed inorganic Hg and not fish-derived MeHg. Hair
      samples from Indonesian gold miners who eat fish daily displayed a wider range of
      positive Delta(199)Hg values (0.21-1.320/00, n=5) and percentages of total Hg as
      MeHg (32-72%, n=4). This suggests that total Hg in the hair samples from
      Indonesian gold miners is likely a mixture of ingested fish MeHg and exogenously
      adsorbed inorganic Hg. Based on data from both populations, we suggest that total
      Hg concentrations in hair samples from small-scale gold miners likely
      overestimate exposure to MeHg from fish consumption. 

PMID- 25577190
TI  - Group CBT for psychosis: a longitudinal, controlled trial with inpatients.
AB  - Individual cognitive behaviour therapy for psychosis (CBTp) is a recommended
      treatment in the acute phase and beyond. However, less is known about the
      effectiveness of group CBTp in acute care. This mixed methods study explored the
      implementation and effectiveness of brief group CBTp with inpatients. This
      prospective trial compared inpatients who received either a four week group CBTp
      program or treatment as usual (TAU). Participants (n = 113 at baseline) completed
      self-report measures of distress, confidence and symptoms of psychosis at
      baseline, post-intervention and one month follow up. CBTp group participants also
      completed a brief open-ended satisfaction questionnaire. Using complete case
      analysis participants who received CBTp showed significantly reduced distress at
      follow up compared to TAU and significantly increased confidence across the study
      and follow up period. However, these effects were not demonstrated using a more
      conservative intention-to-treat analysis. Qualitative analysis of the
      satisfaction data revealed positive feedback with a number of specific themes.
      The study suggests that brief group CBTp with inpatients may improve confidence
      and reduce distress in the longer term. Participants report that the groups are
      acceptable and helpful. However, given the methodological limitations involved in
      this 'real world' study more robust evidence is needed. 

PMID- 25577189
TI  - Randomized controlled pilot trial of a novel dissonance-based group treatment for
      eating disorders.
AB  - The authors conducted a pilot trial of a new dissonance-based group eating
      disorder treatment designed to be a cost-effective front-line transdiagnostic
      treatment that could be more widely disseminated than extant individual or family
      treatments that are more expensive and difficult to deliver. Young women with a
      DSM-5 eating disorder (N = 72) were randomized to an 8-week dissonance-based
      Counter Attitudinal Therapy group treatment or a usual care control condition,
      completing diagnostic interviews and questionnaires at pre, post, and 2-month
      follow-up. Intent-to-treat analyses revealed that intervention participants
      showed greater reductions in outcomes than usual care controls in a multivariate
      multilevel model (chi(2)[6] = 34.1, p < .001), producing large effects for thin
      ideal internalization (d = .79), body dissatisfaction (d = 1.14), and blinded
      interview-assessed eating disorder symptoms (d = .95), and medium effects for
      dissonance regarding perpetuating the thin ideal (d = .65) and negative affect (d
      = .55). Midway through this pilot we refined engagement procedures, which was
      associated with increased effect sizes (e.g., the d for eating disorder symptoms
      increased from .51 to 2.30). This new group treatment produced large reductions
      in eating disorder symptoms, which is encouraging because it requires about
      1/20th the therapist time necessary for extant individual and family treatments,
      and has the potential to provide a cost-effective and efficacious approach to
      reaching the majority of individuals with eating disorders who do not presently
      received treatment.

PMID- 25577191
TI  - CodABC: a computational framework to coestimate recombination, substitution, and
      molecular adaptation rates by approximate Bayesian computation.
AB  - The estimation of substitution and recombination rates can provide important
      insights into the molecular evolution of protein-coding sequences. Here, we
      present a new computational framework, called "CodABC," to jointly estimate
      recombination, substitution and synonymous and nonsynonymous rates from coding
      data. CodABC uses approximate Bayesian computation with and without regression
      adjustment and implements a variety of codon models, intracodon recombination,
      and longitudinal sampling. CodABC can provide accurate joint parameter estimates
      from recombining coding sequences, often outperforming maximum-likelihood methods
      based on more approximate models. In addition, CodABC allows for the inclusion of
      several nuisance parameters such as those representing codon frequencies,
      transition matrices, heterogeneity across sites or invariable sites. CodABC is
      freely available from http://code.google.com/p/codabc/, includes a GUI, extensive
      documentation and ready-to-use examples, and can run in parallel on multicore
      machines. 

PMID- 25577192
TI  - Who should decide how much and what information is important in person-centred
      health care?
AB  - Most guidelines for clinical practice, and especially those for the construction
      of decision support tools, assume that the individual person (the patient) needs
      to be in possession of information of particular sorts and amount in order to
      qualify as having made an 'informed decision'. This often implicitly segues into
      the patient having made a 'good decision'. In person-centred health care,
      whether, in what form, and with what weight, 'information' is included as a
      criterion of decision quality is a matter for the person involved, to decide in
      the light of their own values, preferences, and time and resource constraints. 

PMID- 25577193
TI  - Experimental myositis inducible with transfer of dendritic cells presenting a
      skeletal muscle C protein-derived CD8 epitope peptide.
AB  - It is suggested that polymyositis, an autoimmune inflammatory myopathy, is
      mediated by autoaggressive CD8 T cells. Skeletal muscle C protein is a self
      antigen that induces C protein-induced myositis, a murine model of polymyositis.
      To establish a new murine model of myositis inducible with a single CD8 T-cell
      epitope peptide that derives from the C protein, three internet-based prediction
      systems were employed to identify 24 candidate peptides of the immunogenic
      fragment of the C protein and bind theoretically to major histocompatibility
      complex class I molecules of C57BL/6 (B6) mice. RMA-S cell assay revealed that a
      HILIYSDV peptide, amino acid position 399-406 of the C protein, had the highest
      affinity to the H2-K(b) molecules. Transfer of mature bone marrow-derived
      dendritic cells pulsed with HILIYSDV induced myositis in naive B6 mice. This
      myositis was suppressed by anti-CD8-depleting antibodies but not by anti-CD4
      depleting antibodies. Because this myositis model is mediated by CD8 T cells
      independently of CD4 T cells, it should be a useful tool to investigate pathology
      of polymyositis and develop therapies targeting CD8 T cells. 

PMID- 25577194
TI  - Association between sHLA-G and HLA-G 14-bp deletion/insertion polymorphism in
      Crohn's disease.
AB  - The aim of this study was to evaluate the association between the HLA-G 14-bp
      deletion/insertion (Del/Ins) polymorphism and soluble (s) HLA-G production in
      patients with Crohn's disease (CD). We analyzed also the sHLA-G molecules by
      ELISA and western blot in plasma samples. Among unselected patients, the 14-bp
      Del/Ins polymorphism was not significantly associated with increased CD risk
      neither for alleles (P = 0.371) nor for genotypes (P = 0.625). However, a
      significant association was reported between the 14-bp Del/Ins polymorphism and
      CD, in particular in young-onset CD patients for alleles [P = 0.020, odds ratio
      (OR) = 2.438, 95% confidence interval (CI): 1.13-5.25] but not with adult-onset
      CD patients. A significant association was reported concerning the genotype
      Ins/Ins for young-onset CD patients (P = 0.029, OR = 3.257, 95% CI: 1.08-9.77).
      We observed also a significant increase in sHLA-G measured by ELISA in CD
      patients compared to controls (P = 0.002). The 14-bp Del/Del and 14-bp Del/Ins
      genotypes are the high HLA-G producers. Among sHLA-G(positive) patients, 43% of
      subjects present dimers of HLA-G. The presence of dimers seems to be related to
      the advanced stages of the disease. The 14-bp Del/Ins polymorphism is associated
      with an increased risk of CD particularly in young-onset CD patients and controls
      sHLA-G plasma levels. Dimers of sHLA-G are frequent in advanced disease stages.
      The above findings indicate that the genetic 14-bp Del/Ins polymorphism in exon 8
      of the HLA-G gene is associated with the risk of CD and suggest a role for sHLA-G
      as a prognostic marker for progressive disease.

PMID- 25577195
TI  - Influence of particle size on persistence and clearance of aerosolized silver
      nanoparticles in the rat lung.
AB  - The growing use of silver nanoparticles (AgNPs) in consumer products raises
      concerns about potential health effects. This study investigated the persistence
      and clearance of 2 different size AgNPs (20 and 110 nm) delivered to rats by
      single nose-only aerosol exposures (6 h) of 7.2 and 5.4 mg/m(3), respectively.
      Rat lung tissue was assessed for silver accumulations using inductively-coupled
      plasma mass spectrometry (ICP-MS), autometallography, and enhanced dark field
      microscopy. Involvement of tissue macrophages was assessed by scoring of silver
      staining in bronchoalveolar lavage fluid (BALF). Silver was abundant in most
      macrophages at 1 day post-exposure. The group exposed to 20 nm AgNP had the
      greatest number of silver positive BALF macrophages at 56 days post-exposure.
      While there was a significant decrease in the amount of silver in lung tissue at
      56 days post-exposure compared with 1 day following exposure, at least 33% of the
      initial delivered dose was still present for both AgNPs. Regardless of particle
      size, silver was predominantly localized within the terminal bronchial/alveolar
      duct junction region of the lung associated with extracellular matrix and within
      epithelial cells. Inhalation of both 20 and 110 nm AgNPs resulted in a
      persistence of silver in the lung at 56 days post-exposure and local deposition
      as well as accumulation of silver at the terminal bronchiole alveolar duct
      junction. Further the smaller particles, 20 nm AgNP, produced a greater silver
      burden in BALF macrophages as well as greater persistence of silver positive
      macrophages at later timepoints (21 and 56 days). 

PMID- 25577196
TI  - Metabolomic characteristics of arsenic-associated diabetes in a prospective
      cohort in Chihuahua, Mexico.
AB  - Chronic exposure to inorganic arsenic (iAs) has been linked to an increased risk
      of diabetes, yet the specific disease phenotype and underlying mechanisms are
      poorly understood. In the present study we set out to identify iAs exposure
      associated metabolites with altered abundance in nondiabetic and diabetic
      individuals in an effort to understand the relationship between exposure,
      metabolomic response, and disease status. A nested study design was used to
      profile metabolomic shifts in urine and plasma collected from 90 diabetic and 86
      nondiabetic individuals matched for varying iAs concentrations in drinking water,
      body mass index, age, and sex. Diabetes diagnosis was based on measures of
      fasting plasma glucose and 2-h blood glucose. Multivariable models were used to
      identify metabolites with altered abundance associated with iAs exposure among
      diabetic and nondiabetic individuals. A total of 132 metabolites were identified
      to shift in urine or plasma in response to iAs exposure characterized by the sum
      of iAs metabolites in urine (U-tAs). Although many metabolites were altered in
      both diabetic and nondiabetic 35 subjects, diabetic individuals displayed a
      unique response to iAs exposure with 59 altered metabolites including those that
      play a role in tricarboxylic acid cycle and amino acid metabolism. Taken
      together, these data highlight the broad impact of iAs exposure on the human
      metabolome, and demonstrate some specificity of the metabolomic response between
      diabetic and nondiabetic individuals. These data may provide novel insights into
      the mechanisms and phenotype of diabetes associated with iAs exposure. 

PMID- 25577197
TI  - Patulin induces apoptosis through ROS-mediated endoplasmic reticulum stress
      pathway.
AB  - Patulin (PAT) is a toxic metabolite produced by several filamentous fungi of the
      genera of Penicillium, Aspergillus, and Byssochlamys. PAT is the most common
      mycotoxin found in apples and apple-based products including juice, compotes,
      cider, and baby food. Exposure to this mycotoxin has been reported to induce
      intestinal and kidney injuries. This study investigated the mechanism of PAT
      induced toxicity in human colon carcinoma (HCT116) and embryonic kidney cells
      (HEK293). We demonstrated that PAT activated endoplasmic reticulum (ER) and
      unfolded protein response as evidenced by up-regulation of GRP78 and GADD34,
      splicing of XBP1 mRNA, and expression of the proapoptotic factor CHOP. This ER
      stress response was accompanied by the induction of the mitochondrial apoptotic
      pathway. Apoptosis occurred with ROS production, drop in mitochondrial membrane
      potential and caspase activation. Further, we showed that deficiency of the
      proapoptotic protein Bax or Bak protected cells against PAT-induced apoptosis.
      The treatment of cells with the ROS scavenger N-acetyl cysteine inhibits the ER
      stress response and prevents mitochondrial apoptosis. Collectively, our data
      provide new mechanistic insights in the signaling pathways of the cell death
      induced by PAT and demonstrate that PAT induces cytotoxicity through a ROS
      dependent mechanism involving ER stress and activation of mitochondrial apoptotic
      pathway in human intestinal and kidney cells. 

PMID- 25577198
TI  - Evolutionary patterns in coiled-coils.
AB  - Models of protein evolution are used to describe evolutionary processes, for
      phylogenetic analyses and homology detection. Widely used general models of
      protein evolution are biased toward globular domains and lack resolution to
      describe evolutionary processes for other protein types. As three-dimensional
      structure is a major constraint to protein evolution, specific models have been
      proposed for other types of proteins. Here, we consider evolutionary patterns in
      coiled-coil forming proteins. Coiled-coils are widespread structural domains,
      formed by a repeated motif of seven amino acids (heptad repeat). Coiled-coil
      forming proteins are frequently rods and spacers, structuring both the
      intracellular and the extracellular spaces that often form protein interaction
      interfaces. We tested the hypothesis that due to their specific structure the
      associated evolutionary constraints differ from those of globular proteins. We
      showed that substitution patterns in coiled-coil regions are different than those
      observed in globular regions, beyond the simple heptad repeat. Based on these
      substitution patterns we developed a coiled-coil specific (CC) model that in the
      context of phylogenetic reconstruction outperforms general models in tree
      likelihood, often leading to different topologies. For multidomain proteins
      containing both a coiled-coil region and a globular domain, we showed that a
      combination of the CC model and a general one gives higher likelihoods than a
      single model. Finally, we showed that the model can be used for homology
      detection to increase search sensitivity for coiled-coil proteins. The CC model,
      software, and other supplementary materials are available at
      http://www.evocell.org/cgl/resources (last accessed January 29, 2015).

PMID- 25577199
TI  - Comparative analysis of transposable elements highlights mobilome diversity and
      evolution in vertebrates.
AB  - Transposable elements (TEs) are major components of vertebrate genomes, with
      major roles in genome architecture and evolution. In order to characterize both
      common patterns and lineage-specific differences in TE content and TE evolution,
      we have compared the mobilomes of 23 vertebrate genomes, including 10
      actinopterygian fish, 11 sarcopterygians, and 2 nonbony vertebrates. We found
      important variations in TE content (from 6% in the pufferfish tetraodon to 55% in
      zebrafish), with a more important relative contribution of TEs to genome size in
      fish than in mammals. Some TE superfamilies were found to be widespread in
      vertebrates, but most elements showed a more patchy distribution, indicative of
      multiple events of loss or gain. Interestingly, loss of major TE families was
      observed during the evolution of the sarcopterygian lineage, with a particularly
      strong reduction in TE diversity in birds and mammals. Phylogenetic trends in TE
      composition and activity were detected: Teleost fish genomes are dominated by DNA
      transposons and contain few ancient TE copies, while mammalian genomes have been
      predominantly shaped by nonlong terminal repeat retrotransposons, along with the
      persistence of older sequences. Differences were also found within lineages: The
      medaka fish genome underwent more recent TE amplification than the related
      platyfish, as observed for LINE retrotransposons in the mouse compared with the
      human genome. This study allows the identification of putative cases of
      horizontal transfer of TEs, and to tentatively infer the composition of the
      ancestral vertebrate mobilome. Taken together, the results obtained highlight the
      importance of TEs in the structure and evolution of vertebrate genomes, and
      demonstrate their major impact on genome diversity both between and within
      lineages.

PMID- 25577200
TI  - Genome-wide analysis of adaptive molecular evolution in the carnivorous plant
      Utricularia gibba.
AB  - The genome of the bladderwort Utricularia gibba provides an unparalleled
      opportunity to uncover the adaptive landscape of an aquatic carnivorous plant
      with unique phenotypic features such as absence of roots, development of water
      filled suction bladders, and a highly ramified branching pattern. Despite its
      tiny size, the U. gibba genome accommodates approximately as many genes as other
      plant genomes. To examine the relationship between the compactness of its genome
      and gene turnover, we compared the U. gibba genome with that of four other
      eudicot species, defining a total of 17,324 gene families (orthogroups). These
      families were further classified as either 1) lineage-specific
      expanded/contracted or 2) stable in size. The U. gibba-expanded families are
      generically related to three main phenotypic features: 1) trap physiology, 2) key
      plant morphogenetic/developmental pathways, and 3) response to environmental
      stimuli, including adaptations to life in aquatic environments. Further scans for
      signatures of protein functional specialization permitted identification of seven
      candidate genes with amino acid changes putatively fixed by positive Darwinian
      selection in the U. gibba lineage. The Arabidopsis orthologs of these genes (AXR,
      UMAMIT41, IGS, TAR2, SOL1, DEG9, and DEG10) are involved in diverse plant
      biological functions potentially relevant for U. gibba phenotypic
      diversification, including 1) auxin metabolism and signal transduction, 2)
      flowering induction and floral meristem transition, 3) root development, and 4)
      peptidases. Taken together, our results suggest numerous candidate genes and gene
      families as interesting targets for further experimental confirmation of their
      functional and adaptive roles in the U. gibba's unique lifestyle and highly
      specialized body plan.

PMID- 25577201
TI  - Impact of weight loss diet associated with flaxseed on inflammatory markers in
      men with cardiovascular risk factors: a clinical study.
AB  - BACKGROUND: Flaxseed has received attention for its anti-inflammatory and
      antioxidant role. The present study hypothesizes if flaxseed added to a weight
      loss diet could improve the lipid and metabolic profiles and decrease risk
      factors related to cardiovascular disease. METHODS: In a prospective, single
      blinded 42 days protocol, subjects were allocated into two groups with low
      carbohydrates intake: GriceLC (35% of carbohydrate and 60g of raw rice powder per
      day) and GflaxLC (32% of carbohydrate and 60g of flaxseed powder per day). Blood
      pressure, anthropometric measures and serum levels of isoprostane, C-reactive
      protein, Tumor Necrosis Factor-alpha, glucose, lipidic profile, uric acid,
      adiponectin, leptin and insulin were measured at baseline and at the end of
      interventions. Serum and urinary enterodiol and enterolactione were also
      measured. RESULTS: A total of 27 men with cardiovascular risk factors were
      evaluated, with mean age of 33 +/- 10 years to GriceLC and 40 +/- 9 years to
      GflaxLC. Both groups experienced weight loss and systolic blood pressure
      reduction. A decrease in inflammatory markers (CRP and TNF-alpha) was observed
      after flaxseed intake (mean decrease of 25% and 46% for GflaxLC respectively).
      All groups also showed improvement in levels of total cholesterol, LDL-c, uric
      acid and adiponectin. Only GflaxLC group showed a decrease in triglyceride
      levels. CONCLUSION: This study suggests that flaxseed added to a weight loss diet
      could be an important nutritional strategy to reduce inflammation markers such as
      CRP and TNF-alpha. TRIAL REGISTRATION: ClinicalTrials.gov NCT02132728.

PMID- 25577202
TI  - Prevalence of birth defects in an Arctic Russian setting from 1973 to 2011: a
      register-based study.
AB  - BACKGROUND: Birth defects (BD) constitute an important public health issue as
      they are the main cause of infant death. Their prevalence in Europe for 2008-2012
      was 25.6 per 1000 newborns. To date, there are no population-based studies for
      the Russian Federation. The aim of the present study is to estimate the
      prevalence of BD, its forms, and changes over time in the Russian Arctic city of
      Monchegorsk (Murmansk County) for the period 1973-2011. METHODS: The Murmansk
      County Birth Register and the Kola Birth Register were the primary sources of
      information, covering 30448 pregnancy outcomes in Monchegorsk (Murmansk County,
      Russia) during the study period. RESULTS: The total perinatal prevalence of BD
      was 36.1/1000 live births (LB) and stillborn (SB) (95% CI = 34.0-38.2). After
      exclusions of minor malformations according to the European Surveillance of
      Congenital Anomalies guidelines, it decreased to 26.5/1000 LB plus SB (95% CI =
      24.6-28.3). The perinatal prevalence of BD that are obligatory to report in
      Russia was 7.3/1000 LB plus SB (95% CI = 6.4-8.3). There was a significant
      positive time-trend in total perinatal prevalence of birth defects across the
      study period (p < 0.001 for trend). Prevalence of all BD increased from 23.5/1000
      to 46.3/1000 (LB plus SB), while that excluding minor defects rose from 17.7/1000
      to 35.7/1000 (LB plus SB). The most prevalent group of defects was malformations
      of the musculoskeletal system, which represented 35.4% of all BD. The most
      prominent increase was observed for the urinary system, rising from 0.2/1000 to
      19.1/1000 (LB plus SB). CONCLUSIONS: The observed perinatal prevalence of BD in
      Monchegorsk increased two-fold during the 38-year study period. Further
      investigations to identify the underlying bases for the observed progressive
      growth in BD are recommended.

PMID- 25577203
TI  - Effects of Lactobacillus acidophilus dietary supplementation on the performance,
      intestinal barrier function, rectal microflora and serum immune function in
      weaned piglets challenged with Escherichia coli lipopolysaccharide.
AB  - This study was conducted with a lipopolysaccharide (LPS)-challenged piglet model
      to determine the effects of diets containing Lactobacillus acidophilus on the
      performance, intestinal barrier function, rectal microflora and serum immune
      function. A total of 150 piglets (initial body weight (BW) 7.53 +/- 0.21 kg) were
      allotted to one of the following diets, including a basal diet, a basal diet
      supplemented with 250 mg/kg Flavomycin, or basal diet plus 0.05, 0.1 or 0.2 % L.
      acidophilus. On day 28 of the trial, the pigs were given an intraperitoneal
      injection of LPS (200 MUg/kg body weight) followed by blood collection 3 h later.
      Diets with either antibiotics, 0.1 or 0.2 % Lactobacillus increased (P < 0.05)
      the final BW and decreased (P < 0.05) feed gain ratio (F/G) compared with the
      control group. Pigs fed diets containing antibiotic or Lactobacillus had greater
      average daily gain (ADG) (P < 0.05) than pigs fed the control diet. The rectal
      content Lactobacillus counts for pigs fed diet containing Lactobacillus were
      significant higher (P < 0.01) than those fed antibiotic or control diet. Feeding
      the Lactobacillus diets decreased the Escherichia coli counts of rectal content
      (P < 0.01). Pigs fed diets containing 0.1 or 0.2 % Lactobacillus decreased serum
      DAO activity (P < 0.05) compared with pigs fed the control diet. Serum IL-10
      concentration was enhanced in pigs fed the diet with Lactobacillus compared to
      pigs fed the control diet and antibiotic diet. Feeding a diet with Lactobacillus
      reduced (P < 0.05) IFN-gamma concentration compared to the control diet.
      Inclusion of Lactobacillus in diets fed to pigs reduced TNF-alpha concentration
      compared with pigs fed no Lactobacillus (P < 0.05). These results indicate that
      feeding with L. acidophilus improved growth performance and protected against LPS
      induced inflammatory status. 

PMID- 25577205
TI  - Free manual of cadaver dissection modifiable by other anatomists.
AB  - Even in the rapidly changing field of cadaver dissection, published guide books
      still play an important role in the anatomy lab. However, commercial manuals with
      lengthy volumes and inflexible copyrights have several limitations which can be
      complemented by open-source manuals. Recently, the authors have manufactured and
      distributed a free electronic dissection manual (anatomy.co.kr), where
      descriptions are written concisely and images are drawn schematically. Moreover,
      simplified signs are employed to represent the cadaver viewing angles and manner
      of dissection. Based on the original files of this manual, other anatomists can
      revise and utilize the descriptions and figures. We expect many updated versions
      of our manual to be shared between students all over the world.

PMID- 25577204
TI  - Emcibacter nanhaiensis gen. nov. sp. nov., isolated from sediment of the South
      China Sea.
AB  - A new aerobic, Gram stain-negative, oxidase- and catalase- positive, ovoid or rod
      shaped bacterial strain, designated HTCJW17(T), was isolated from a sediment
      collected from the South China Sea and subjected to a polyphasic taxonomic
      characterization. The isolate forms small, creamy-white, opaque and circular
      colonies on agar plates. Growth occurs between 15 and 45  degrees C, 1-7 % (w/v)
      NaCl and pH 6-9. Phylogenetic analysis based on 16S rRNA gene sequences showed
      that strain HTCJW17(T) belongs to the family Kordiimonadaceae of the order
      Kordiimonadales, with highest sequence similarity to Kordiimonas gwangyangensis
      GW14-5(T) (91.1 %). The major fatty acids were identified to be summed feature 8
      (C18:1 omega7c/omega6c; 56.6 %), C14:0 (8.5 %), C14:0 2-OH (8.4 %), summed
      feature 3 (C16:1 omega7c/C16:1 omega6c; 6.2 %), and C16:0 (5.2 %). The polar
      lipids were determined to be phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylglycerol, six unidentified glycolipids and two unidentified
      phospholipids. The respiratory quinone was identified as ubiquinone Q-10. The
      genomic DNA G+C content was determined to be 56.3 mol%. On the basis of
      genotypic, chemotaxonomic and phenotypic distinctness, we propose a novel genus,
      Emcibacter gen. nov., with Emcibacter nanhaiensis sp. nov. as the type species.
      The type strain is HTCJW17(T) (=CGMCC 1.12471(T) = LMG 27419(T) = MCCC
      1A06723(T)). 

PMID- 25577206
TI  - The blessingway ceremony: ritual, nostalgic imagination and feminist
      spirituality.
AB  - There is an increasing interest in the role of spirituality on the experience of
      health, wellness and illness, as well as the role of spiritual practice in health
      care provision. For pregnancy and childbirth, this focus has tended to
      concentrate on hospital birth settings and care, and religious forms of
      spirituality. The blessingway ceremony can be described as an alternative baby
      shower, popular with home-birthing women. Its focus is woman-centred and draws on
      the power of ritual to evoke a spiritual experience for the pregnant host and her
      guests. This spirituality is experienced as a strong connection between women,
      their relationship with 'nature', and forged via the nostalgic imagination of
      women through time and space. This article will draw on data obtained in 2010
      during doctoral fieldwork with 52 home-birthing women across eastern Australia
      and will examine the blessingway ceremony and its significance as a site of
      potential spiritual empowerment for pregnant and birthing women. 

PMID- 25577207
TI  - Electrochemical behavior and corrosion resistance of Ti-15Mo alloy in naturally
      aerated solutions, containing chloride and fluoride ions.
AB  - The electrochemical behavior and corrosion resistance of Ti-15Mo alloy to
      applications as biomaterials in solutions 0.15 mol L(-1) Ringer, 0.15 mol L(-1)
      Ringer plus 0.036 mol L(-1) NaF and 0.036 mol L(-1) NaF (containing 1,500 ppm of
      fluoride ions, F(-)) were investigated using open-circuit potential, cyclic
      voltammetry, and electrochemical impedance spectroscopy techniques, X-ray
      photoelectron spectroscopy and scanning electron microscope. Corrosion resistance
      and electrochemical stability of the Ti-15Mo alloy decreased in solutions
      containing F(-) ions. In all cases, there were formation and growth of TiO2 and
      MoO3 (a protector film), not being observed pitting corrosion, which might enable
      Ti-15Mo alloys to be used as biomedical implant, at least in the studied
      conditions, since the electrochemical stability and corrosion resistance of the
      passive films formed are necessary conditions for osseointegration.

PMID- 25577208
TI  - Bioactive IGF-1 release from collagen-GAG scaffold to enhance cartilage repair in
      vitro.
AB  - Tissue engineering is a promising technique for cartilage repair. Toward this
      goal, a porous collagen-glycosaminoglycan (CG) scaffold was loaded with different
      concentrations of insulin-like growth factor-1 (IGF-1) and evaluated as a growth
      factor delivery device. The biological response was assessed by monitoring the
      amount of type II collagen and proteoglycan synthesised by the chondrocytes
      seeded within the scaffolds. IGF-1 release was dependent on the IGF-1 loading
      concentration used to adsorb IGF-1 onto the CG scaffolds and the amount of IGF-1
      released into the media was highest at day 4. This initial IGF-1 release could be
      modelled using linear regression analysis. Osteoarthritic (OA) chondrocytes
      seeded within scaffolds containing adsorbed IGF-1 deposited decorin and type II
      collagen in a dose dependent manner and the highest type II collagen deposition
      was achieved via loading the scaffold with 50 MUg/ml IGF-1. Cells seeded within
      the IGF-1 loaded scaffolds also deposited more extracellular matrix than the no
      growth factor control group thus the IGF-1 released from the scaffold remained
      bioactive and exerted an anabolic effect on OA chondrocytes. The effectiveness of
      adsorbing IGF-1 onto the scaffold may be due to protection of the molecule from
      proteolytic digestion allowing a more sustained release of IGF-1 over time
      compared to adding multiple doses of exogenous growth factor. Incorporating IGF-1
      into the CG scaffold provided an initial therapeutic burst release of IGF-1 which
      is beneficial in initiating ECM deposition and repair in this in vitro model and
      shows potential for developing this delivery device in vivo. 

PMID- 25577209
TI  - Bone regeneration using a freeze-dried 3D gradient-structured scaffold
      incorporating OIC-A006-loaded PLGA microspheres based on beta-TCP/PLGA.
AB  - To reveal the latent capacity of the growth factor-like low-molecular-weight
      material OIC-A006 in tissue regeneration, it is essential to design a porous
      scaffold in order to concurrently accommodate cells and drug release in a
      controlled manner. Consequently, we fabricated poly (L-lactide-co-glycolide)
      (PLGA)-based microspheres with an OIC-A006-loaded gradient-structured beta
      TCP/PLGA scaffold by freeze-drying which could then be used for drug delivery and
      bone regeneration. The OIC-A006-loaded beta-TCP/PLGA scaffold consisted of two
      parts which loaded different doses of OIC-A006 (6.25 MUM, outside; 12.5 MUM,
      inside). The porosity, compressive strength, SEM, degradation, and cumulative
      amount of drug release in vitro were characterized. Furthermore, we confirmed the
      incorporation of OIC-A006 into the PLGA-based microspheres within the scaffolds
      using UV-spectrophotometry, and the amount of drug remaining in the scaffold was
      maintained by 10 % for up to 28 days. The drug release was slower in the normal
      structured drug-loaded scaffold. The OIC-A006 released action from the OIC-A006
      loaded beta-TCP/PLGA scaffold with ideal therapeutic prospects in tissue
      regeneration. In vitro cell culture results showed that this gradient-structured
      composite scaffold can induce the adhesion and proliferation of rat bone marrow
      stromal cells towards osteoblasts. These results showed that the newly developed
      OIC-A006-loaded scaffolds with gradient structure can be potentially applied to
      bone regeneration in clinical applications.

PMID- 25577210
TI  - Cross-linked poly(acrylic acids) microgels and agarose as semi-interpenetrating
      networks for resveratrol release.
AB  - Carbomers, cross-linked poly(acrylic acid) microgels, have been widely used in
      pharmaceutical formulations as swollen hydrogels. Agarose, whose
      thermoreversibility may be exploited for drug loading, forms a gel with a
      mechanism involving coil-helix transition at about 36  degrees C. In this work
      carbomer microgels were combined with agarose networks in a semi-interpenetrating
      polymer network structure, aiming at obtaining suitable delivery systems for the
      loading and release of molecules with poor bioavailability but high therapeutic
      interest, like resveratrol. The rheological properties of the formulations and
      their in vitro cytocompatibility were studied and optimized acting on the
      neutralizing agent (triethylamine (N,N-diethylethanamine), triethanolamine
      (tris(2-hydroxyethyl)amine) and sodium hydroxide) and amount of OH donors (1,2
      propanediol and glycerol). As a preparation method, autoclaving was introduced to
      simultaneously obtain heating and sterilising. Among the different neutralizing
      agents, NaOH was chosen to avoid the use of amines, considering the final
      application. Without the addition of alcohols as typical OH donors to induce
      Carbomer gelification, gels with appropriate rheological properties and stability
      were produced. For this formulation, the release of resveratrol after 7 days was
      about 80 % of the loaded mass, suggesting it is an interesting approach to be
      exploited for the development of innovative resveratrol delivery systems.

PMID- 25577211
TI  - Biomechanical properties of hybrid heart valve prosthesis utilizing the pigs that
      do not express the galactose-alpha-1,3-galactose (alpha-Gal) antigen derived
      tissue and tissue engineering technique.
AB  - The aim of the study was to estimate the biomechanical properties of heart valves
      conduit derived from transgenic pigs to determine the usefulness for the
      preparation of tissue-engineered heart valves. The acellular aortic and pulmonary
      valve conduits from transgenic pigs were used to estimate the biomechanical
      properties of the valve. Non-transgenic porcine heart valve conduits were used as
      a reference. The biomechanics stability of acellular valve conduits decreased
      both for the transgenic and non-transgenic porcine valves. The energy required to
      break the native pulmonary valve derived from transgenic pigs was higher (20,475
      +/- 7,600 J m(-2)) compared with native non-transgenic pigs (12,140 +/- 5,370 J
      m(-2)). After acellularization, the energy to break the valves decreased to
      14,600 and 8,800 J m(-2) for the transgenic pulmonary valve and non-transgenic
      valve, respectively. The native transgenic pulmonary valve showed a higher
      extensibility (42.70 %) than the non-transgenic pulmonary valve (35.50 %); the
      extensibility decreased after acellularization to 41.1 and 31.5 % for the
      transgenic and non-transgenic valves, respectively. The pulmonary valves derived
      from transgenic pigs demonstrate better biomechanical properties compared with
      non-transgenic. Heart valves derived from transgenic pigs can be valuable for the
      preparation of tissue-engineered bioprostheses, because of their biomechanical
      properties, stability, reduced immune response, making them safer for clinical
      applications. 

PMID- 25577212
TI  - Green synthesis of platinum nanoparticles that induce cell death and G2/M-phase
      cell cycle arrest in human cervical cancer cells.
AB  - Platinum-based chemotherapeutic drugs, including cisplatin, carboplatin, and
      oxaliplatin, have been used to manage cancer in spite of dose-dependent side
      effects, including nephrotoxicity, neurotoxicity and ototoxicity. These
      disadvantages have prompted the development of new strategies for cancer therapy
      that utilize functionalized nanoparticles as nanomedicines. In the present
      investigation, we have synthesized platinum nanoparticles using tea polyphenol
      (TPP) as both a reducing and surface modifying agent. The crystalline nature and
      morphology of the prepared TPP-functionalized platinum nanoparticles (TPP@Pt)
      were analyzed using X-ray diffraction (XRD) and transmission electron microscopy
      (TEM). The XRD results revealed that the TPP@Pt had a crystalline nature with a
      face-centered cubic structure. TEM imaging suggested that the TTP@Pt are flower
      shaped with a well-dispersed 30-60 nm-sized TPP@Pt formation. Cervical cancer
      cells (SiHa) were then treated with different concentrations of TPP@Pt. The
      effects of TPP@Pt on cell viability, nuclear morphology and cell cycle
      distribution were investigated. A cell viability assay revealed that the
      proliferation of SiHa cells was inhibited by TPP@Pt. Propidium iodide nuclear
      staining indicated that TPP@Pt induced nuclear fragmentation and chromatin
      condensation. Treatment with TPP@Pt significantly increased the percentage of
      cells in the G2/M phase, which indicates induced cell cycle arrest in the G2/M
      phase and an increased number of cells in the subG0 cell death phase. These
      findings highlight a potential use of TPP@Pt in cervical cancer treatment. 

PMID- 25577214
TI  - Tribological and mechanical performance evaluation of metal prosthesis components
      manufactured via metal injection molding.
AB  - The increasing number of total joint replacements, in particular for the knee
      joint, has a growing impact on the healthcare system costs. New cost-saving
      manufacturing technologies are being explored nowadays. Metal injection molding
      (MIM) has already demonstrated its suitability for the production of CoCrMo alloy
      tibial trays, with a significant reduction in production costs, by holding both
      corrosion resistance and biocompatibility. In this work, mechanical and
      tribological properties were evaluated on tibial trays obtained via MIM and
      conventional investment casting. Surface hardness and wear properties were
      evaluated through Vickers hardness, scratch and pin on disk tests. The MIM and
      cast finished tibial trays were then subjected to a fatigue test campaign in
      order to obtain their fatigue load limit at 5 millions cycles following ISO 14879
      1 directions. CoCrMo cast alloy exhibited 514 HV hardness compared to 335 HV of
      MIM alloy, furthermore it developed narrower scratches with a higher tendency
      towards microploughing than microcutting, in comparison to MIM CoCrMo. The
      observed fatigue limits were (1,766 +/- 52) N for cast tibial trays and (1,625 +/
      44) N for MIM ones. Fracture morphologies pointed out to a more brittle behavior
      of MIM microstructure. These aspects were attributed to the absence of a fine
      toughening and surface hardening carbide dispersion in MIM grains. Nevertheless,
      MIM tibial trays exhibited a fatigue limit far beyond the 900 N of maximum load
      prescribed by ISO and ASTM standards for the clinical application of these
      devices. 

PMID- 25577213
TI  - The effect of bone marrow concentrate and hyperbaric oxygen therapy on bone
      repair.
AB  - Neoangiogenesis represents an essential part of bone regeneration. Therefore the
      improvement of neovascularization is the subject of various research approaches.
      In addition autologous mesenchymal stem cells concentrate in combination with
      bone substitute materials have been shown to support bone regeneration. In a
      rabbit model we examined the proposed synergistic effect of hyperbaric oxygen
      therapy (HBOT) and bone marrow concentrate (BMC) with porous calcium phosphate
      granules (CPG) on neoangiogenesis and osseous consolidation of a critical- size
      defect. The animal groups treated with HBOT showed a significantly higher
      microvessel density (MVD) by immunhistochemistry. Furthermore HBOT groups
      presented a significantly larger amount of new bone formation
      histomorphometrically as well as radiologically. We conclude that the increase in
      perfusion as a result of increased angiogenesis may play a key role in the
      effects of HBOT and consequently promotes bone healing. 

PMID- 25577215
TI  - Highly biocompatible behaviour and slow degradation of a LDH (layered double
      hydroxide)-coating on implants in the middle ear of rabbits.
AB  - Chronic inflammation can irreversibly damage components of the ossicular chain
      which may lead to sound conduction deafness. The replacement of impaired ossicles
      with prostheses does not reduce the risk of bacterial infections which may lead
      to loss of function of the implant and consequently to additional damage of the
      connected structures such as inner ear, meninges and brain. Therefore, implants
      that could do both, reconstruct the sound conduction and in addition provide
      antibacterial protection are of high interest for ear surgery. Layered double
      hydroxides (LDHs) are promising novel biomaterials that have previously been used
      as an antibiotic-releasing implant coating to curb bacterial infections in the
      middle ear. However, animal studies of LDHs are scarce and there exist only few
      additional data on the biocompatibility and hardly any on the biodegradation of
      these compounds. In this study, middle ear prostheses were coated with an LDH
      compound, using suspensions of nanoparticles of an LDH containing Mg and Al as
      well as carbonate ions. These coatings were characterized and implanted into the
      middle ear of healthy rabbits for 10 days. Analysis of the explanted prostheses
      showed only little signs of degradation. A stable health constitution was
      observed throughout the whole experiment in every animal. The results show that
      LDH-based implant coatings are biocompatible and dissolve only slowly in the
      middle ear. They, therefore, appear as promising materials for the construction
      of controlled drug delivery vehicles.

PMID- 25577216
TI  - Behavior of osteoblasts on TI surface with two different coating designed for
      orthodontic devices.
AB  - In the present study we coated Ti surfaces with polytetrafluorethylene (PTFE) and
      titanium nitride (TiN) and investigated in vitro the behavior of osteoblasts on
      these surfaces. MG-63 osteoblasts were cultured on titanium discs with different
      surface treatment: uncoated Ti6Al4V, TiN-coated, PTFE-coated. Cell
      viability/proliferation was detected by MTT assay. Gene-expression levels of
      alkaline phosphatase (ALP), osteocalcin (OC), type I collagen, receptor activator
      of nuclear factor-kappa-B ligand (RANKL), and osteoprotegerin (OPG) were
      determined by qPCR. Cell behavior on different surfaces was observed by time
      lapse microscopy. Cells grown on PTFE-coated Ti surface exhibited delayed surface
      attachment and decreased proliferation after 48 h. However, after 168 h of
      culture cells grown on PTFE-coated surface exhibited higher
      viability/proliferation, higher expression levels of ALP and OC, and higher
      OPG/RANKL ratio compared to uncoated surface. No effect of TiN-coating on any
      investigated parameter was found. Our results shows that PTFE coating exhibits no
      toxic effect on MG-63 cells and slightly stimulates expression of several genes
      associated with osteogenesis. We propose that PTFE coating could be considered as
      a possible choice for a surface treatment of temporary skeletal anchorage devices
      in orthodontics. 

PMID- 25577217
TI  - Ex vivo alendronate localization at the mesoporous titania implant/bone
      interface.
AB  - An attractive approach in implant technology is local drug delivery, and design
      of efficient, safe and reliable treatments. Our hitherto strategy has been to
      coat Ti implants with a thin mesoporous TiO2 film that in turn is loaded with an
      osteoporosis drug, such as Alendronate (ALN) that is known to suppress
      osteoclastic activity. This system has proven highly successful and results in
      excellent osseointegration. However, more detailed information about drug-release
      and distribution at the bone/implant interface is needed. In this study, (14)C
      ALN loaded titanium implants were placed up to 8 weeks into rat tibia and the
      spatial-temporal distribution of the drug was evaluated. Autoradiography data
      demonstrated a sustained release of (14)C-ALN and the released drug remained
      bound to bone in close vicinity, within 500 micrometers, of the implants. Liquid
      scintillation counting experiments confirmed that the distal transport of
      released (14)C-ALN was extremely low. The results are favorable as they show that
      ALN stays for a long time in the vicinity of the implant and may therefore
      improve for a long time the mechanical fixation of bone anchored implants.
      Moreover, these findings suggest due to the low systemic spreading a minimal risk
      of Alendronate related systemic side effects.

PMID- 25577218
TI  - Ectopic osteogenesis of an injectable nHAC/CSH loaded with blood-acquired
      mesenchymal progenitor cells in a nude mice model.
AB  - An injectable bone cement, nHAC/CSH, which consists of nano
      hydroxyapatite/collagen (nHAC) and calcium sulphate hemihydrate (CaSO4.1/2H2O;
      CSH) was investigated as a tissue-engineered scaffold material with blood
      acquired mesenchymal progenitor cells (BMPCs) as seeding cells. An in vitro study
      on the cytocompatability of nHAC/CSH and an in vivo study on the ectopic bone
      formation of nHAC/CSH loaded with dBMPCs were both conducted. The dBMPCs
      morphology, proliferation, differentiation and apoptosis assays were conducted
      using the direct contact and extract method. The cells tests exhibited normal
      growth and bioactive function in vitro. Studies in vivo showed that this
      injectable tissue engineered bone (ITB) formed bone structure in the heterotopic
      site of nude mice. These findings indicate that the ITB composed of nHAC/CSH and
      dBMPCs may represent a useful strategy for clinical reconstruction of irregular
      bone defects. 

PMID- 25577219
TI  - Hook effect and linear range in prolactin assays: distinct confounding entities.

PMID- 25577220
TI  - Germinoma in the bilateral basal ganglia presented with cognitive deterioration.
AB  - PURPOSE: Here, we report a case of pediatric germinoma located in the bilateral
      basal ganglia, which presented with severe cognitive deteriorations. CASE REPORT:
      A 15-year-old boy presented with decreased school performance and mild cognitive
      disturbances. Magnetic resonance images (MRI) of the brain revealed T2
      hyperintensity in the bilateral basal ganglia. The patient was initially observed
      by a local hospital and had screening for metabolic diseases or inflammatory
      diseases. Lesions with similar characteristics were also found in the pituitary
      stalk and infundibulum, and these lesions were enhanced with gadolinium (Gad). MR
      spectroscopy suggested that these should be neoplastic lesions other than
      metabolic or inflammatory diseases. Biopsy was performed with ventriculoscope,
      which proved all lesions of infundibulum, pineal, and basal ganglia were
      pathologically germinoma. The lesions responded well to the chemotherapy and
      radiation, and his cognitive function improved significantly. CONCLUSION: A case
      of germinoma in the bilateral basal ganglia which significantly affect cognitive
      functions is reported. Differential diagnoses of cognitive symptoms are various,
      but germinoma could be considered as a possible pathology for it. Early MRI and
      tumor marker exams are recommended, unless organic brain diseases are completely
      denied. MR spectroscopy and biopsy with ventriculoscope are useful for diagnosis.

PMID- 25577221
TI  - Influence of tibial rotation in total knee arthroplasty on knee kinematics and
      retropatellar pressure: an in vitro study.
AB  - PURPOSE: Although continuous improvements have been made, there is still a
      considerable amount of unsatisfied patients after total knee arthroplasty (TKA).
      A main reason for this high percentage is anterior knee pain, which is supposed
      to be provoked by post-operative increased retropatellar peak pressure. Since
      rotational malalignment of the implant is believed to contribute to post
      operative pain, the aim of this study was to examine the influence of tibial
      component rotation on knee kinematics and retropatellar pressure. METHODS: Eight
      fresh-frozen knee specimens were tested in a weight-bearing knee rig after fixed
      bearing TKA under a loaded squat from 20 degrees  to 120 degrees  of flexion. To
      examine tibial components with different rotations, special inlays with 3 degrees
      internal rotation and 3 degrees  external rotation were produced and
      retropatellar pressure distribution was measured with a pressure-sensitive film.
      The kinematics of the patella and the femorotibial joint were recorded with an
      ultrasonic-based motion analysis system. RESULTS: Retropatellar peak pressure
      decreased significantly from 3 degrees  internal rotation to neutral position and
      3 degrees  external rotation of the tibial component (8.5 +/- 2.3 vs. 8.2 +/- 2.4
      vs. 7.8 +/- 2.5 MPa). Regarding knee kinematics femorotibial rotation and
      anterior-posterior translation, patella rotation and tilt were altered
      significantly, but relative changes remained minimal. CONCLUSION: Changing tibial
      rotation revealed a high in vitro influence on retropatellar peak pressure. We
      recommend the rotational alignment of the tibial component to the medial third of
      the tibial tuberosity or even more externally beyond that point to avoid anterior
      knee pain after TKA.

PMID- 25577222
TI  - Outcome of subtalar instability reconstruction using the semitendinosus allograft
      tendon and biotenodesis screws.
AB  - PURPOSE: Subtalar instability (STI) has often been obscured by lateral ankle
      instability. Moreover, although there have been several reports of techniques for
      reconstructing STI, no clinical outcome results are known to have been published.
      The authors report the clinical and radiographic outcomes of the ligament
      reconstruction of STI with a recently reported novel technique utilising a
      semitendinosus tendon allograft and interference screws. METHODS: This study is
      based on 20 ankles that underwent ligament reconstruction for STI between 2009
      and 2013. The average follow-up period was 15.0 +/- 5 months, and the average age
      at surgery was 28.1 +/- 10.8 years old. Visual analogue (VAS) pain scores,
      American Orthopedic Foot and Ankle Society (AOFAS) and Karlsson-Peterson ankle
      scores as well as patient satisfaction were evaluated. Radiographic evaluation of
      medial translations of calcaneus and subtalar tilt angles was preformed with
      ankle and Broden's stress radiographs. RESULTS: The VAS pain score decreased from
      6.1 +/- 1.1 preoperatively to 1.8 +/- 1.2 post-operatively (p < 0.05). The AOFAS
      score improved from 66.0 +/- 12.2 preoperatively to 89.6 +/- 6.7 post
      operatively, and the Karlsson-Peterson score improved from 57.0 +/- 13.5 to 91.1
      +/- 6.8 (p < 0.05). There were no complications such as recurred STI or subtalar
      joint stiffness. All of the patients were satisfied with the surgery. Subtalar
      tilt angle decreased from 11.5 degrees  preoperatively to 3.0 degrees  post
      operatively, and the calcaneal medial translations decreased from 7.4 to 3.9 mm.
      CONCLUSION: This is the first report on the comprehensive clinical and
      radiographic outcomes of STI reconstruction using a semitendinosus tendon
      allograft and interference screws. The novel technique of STI reconstruction was
      found to show encouraging clinical outcomes with high patient satisfaction.
      LEVELS OF EVIDENCE: IV.

PMID- 25577223
TI  - Charlson comorbidity index: an additional prognostic parameter for preoperative
      glioblastoma patient stratification.
AB  - PURPOSE: Dismal glioblastoma (GB) patient outcome calls for the elucidation of
      further reliable predictors of prognosis. Established "biomarkers," age and
      functional status, employed in today's patient stratification have limits in
      fingerprinting this heterogeneous tumor entity. We aimed at ascertaining
      additional prognostic factors that may facilitate patient stratification for
      surgery. METHODS: A retrospective review of 233 consecutive adult patients
      operated on for newly diagnosed GB at a single tertiary institution over a 5-year
      period (2006-2011) was conducted. Modern defined outcome associating factors
      recorded included demographics (preoperative age, gender, signs, symptoms,
      comorbidity status quantified by the Charlson comorbidity index (CCI), functional
      status computed by the Karnofsky performance scale (KPS)), tumor characteristics
      (size, location, isocitrate dehydrogenase mutation, and O-6-methylguanine-DNA
      methyltransferase promoter methylation status), and treatment parameters
      (volumetrically quantified extent of resection and adjuvant therapy). Survival
      analysis was performed by the Kaplan-Maier method. Influence of variables was
      evaluated using log-rank test. RESULTS: Median neuroradiographic evidence of
      tumor progression was 6 months after surgery (range 0-72). The median overall
      survival was 9.5 months (range 0-72). Age > 65 years, KPS <= 70, and CCI > 3 were
      significantly associated with both poor OS (each p < 0.0001) and PFS (p < 0.0001,
      p < 0.001 and p < 0.002), respectively. Also, patients older than 65 years
      significantly had a CCI > 3 (p < 0.0001). CONCLUSIONS: Our data evidence that
      aside established prognostic parameters (age and KPS) for GB patient outcome, the
      CCI additionally significantly impacts outcome and may be employed for
      preoperative patient stratification.

PMID- 25577224
TI  - Should KRAS mutation still be used as a routine predictor of response to EGFR
      TKIs in advanced non-small-cell lung cancer? A revaluation based on meta
      analysis.
AB  - PURPOSE: Regarding the controversial investigations characterizing the role of
      KRAS status for predicting patients' response to epidermal growth factor receptor
      tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small-cell lung cancer
      (NSCLC), we conducted a meta-analysis in unselected patients and a further subset
      analysis in EGFR wild-type advanced NSCLC to get a more accurate evaluation.
      METHODS: We did systematically searches following the retrieval strategies. The
      end points were overall survival (OS), progression-free survival (PFS), and
      overall response rate (ORR). RESULTS: Twelve prospective intervention trials
      comprised of 1,859 unselected advanced NSCLC patients were identified. KRAS
      mutation was associated with shorter OS and PFS [hazard ratio (HR) 2.09, 95 %
      confidence interval (CI) 1.56-2.80; HR 1.82, 95 % CI 1.50-2.20] and lower ORR
      (relative ratio 0.25, 95 % CI 0.11-0.59) in unselected advanced NSCLC. After
      subgroup analysis, the association with survival was strengthened in second- or
      later-line EGFR-TKIs treatment group, with an HR of 2.45 for OS (95 % CI 1.27
      4.74) and 1.86 for PFS (95 % CI 1.51-2.29), while the association with response
      to EGFR-TKIs became nonsignificant (P = 0.153). Four retrospective studies on the
      role of KRAS status in EGFR wild-type advanced NSCLC were deemed eligible and
      presented that KRAS mutation was associated with none of the outcomes in EGFR
      wild-type patients treated with EGFR-TKIs. CONCLUSIONS: In unselected advanced
      NSCLC patients, KRAS mutations could be used as a potential negative predictor of
      clinical benefit from EGFR-TKIs. However, KRAS testing is of limited value to
      identify patients for EGFR-TKIs when EGFR status is considered.

PMID- 25577225
TI  - Cardiovascular magnetic resonance imaging-based computational fluid
      dynamics/fluid-structure interaction pilot study to detect early vascular changes
      in pediatric patients with type 1 diabetes.
AB  - We hypothesized that pediatric patients with type 1 diabetes have cardiac
      magnetic resonance (CMR) detectable differences in thoracic aortic wall
      properties and hemodynamics leading to significant local differences in indices
      of wall shear stress, when compared with age-matched control subjects without
      diabetes. Pediatric patients with type 1 diabetes were recruited from Children's
      Hospital of Wisconsin and compared with controls. All underwent morning CMR
      scanning, 4-limb blood pressure, brachial artery reactivity testing, and
      venipuncture. Patient-specific computational fluid dynamics modeling with fluid
      structure interaction, based on CMR data, determined regional time-averaged wall
      shear stress (TAWSS) and oscillatory shear index (OSI). Twenty type 1 diabetic
      subjects, median age 15.8 years (11.6-18.4) and 8 controls 15.4 years (10.3-18.2)
      were similar except for higher glucose, hemoglobin A1c, and triglycerides for
      type 1 diabetic subjects. Lower flow-mediated dilation was seen for those with
      type 1 diabetes (6.5) versus controls (7.8), p = 0.036. For type 1 diabetic
      subjects, the aorta had more regions with high TAWSS when compared to controls.
      OSI maps appeared similar. Flow-mediated dilation positively correlated with age
      at diabetes diagnosis (r = 0.468, p = 0.038) and hemoglobin A1c (r = 0.472, p =
      0.036), but did not correlate with aortic distensibility, TAWSS, or OSI. TAWSS
      did not correlate with any clinical parameter for either group. CMR shows
      regional differences in aortic wall properties for young diabetic patients. Some
      local differences in wall shear stress indices were also observed, but a
      longitudinal study is now warranted.

PMID- 25577226
TI  - Evaluation of cardiotoxicity by tissue Doppler imaging in childhood leukemia
      survivors treated with low-dose anthracycline.
AB  - Improvement in long-term survival in patients with acute childhood leukemia has
      led to the need for monitorization of chemotherapy-related morbidity and
      mortality. This study included 60 patients with acute lymphoblastic leukemia that
      were in remission for at least 2 years and 30 healthy controls. Systolic and
      diastolic function of myocardium was evaluated using conventional
      echocardiography and tissue Doppler imaging of the left ventricle,
      interventricular septum and right ventricle. Median age of patients was 11.7
      years (range 10-14.9 years), and the median duration of remission was 4 years
      (range 2.5-5 years). All patients were treated with a low cumulative dose of
      adriamycin (100 mg/m(2)) according to the St. Jude Total-XIIIA protocol. The
      ejection fraction (EF) and fractional shortening were normal in the patient and
      control groups, even though EF values were significantly lower in the patients
      (69.5 +/- 2.3 vs. 72.7 +/- 3 %, P < 0.01). Myocardial systole (S m), early
      diastole (E m) and late diastole (A m) velocities in all segments of the
      myocardium were significantly lower in the patient group (P < 0.01 for all
      segments). Cardiotoxicity was noted in all segments of the myocardium in the
      patient group, despite the fact that they were all treated with a low cumulative
      dose of adriamycin. Based on these findings, we think that there is no safe dose
      for anthracyclines and periodic echocardiographic evaluation of both the left and
      right ventricles must be performed in all patients treated with anthracyclines,
      even at low doses.

PMID- 25577227
TI  - Oral rehydration salts: an effective choice for the treatment of children with
      vasovagal syncope.
AB  - To explore whether oral rehydration salts (ORS) is effective in the treatment of
      children with vasovagal syncope (VVS). One hundred and sixty-six consecutive
      patients with recurrent syncope and positive head-up tilt testing (HUTT) were
      recruited, randomly divided to conventional therapy (health education and tilt
      training) plus ORS (with 500 ml of water) group (Group I, 87 patients) and
      conventional therapy group (Group II, 79 patients). Therapeutic effect was
      evaluated by changes of syncopal episode and reperformed HUTT response. At the
      end of 6-month follow-up, syncopal episode did not reoccur in 49 (56.3 %)
      patients, decreased in 34 (39.1 %) patients, and had no obvious change or
      increased in four (4.6 %) patients in Group I, and the results were 31 (39.2 %),
      37 (46.8 %), and 11 (14 %) in Group II, respectively. The difference was
      significant (chi (2) = 7.074, P < 0.05). When HUTT was reperformed, 57 (65.5 %)
      and 28 (35.4 %) patients had negative response and 30 (34.5 %) and 51 (64.6 %)
      patients had positive response, respectively, in Group I and Group II. The
      difference was also significant (chi (2) = 13.808, P < 0.01). In Group I, the two
      aspects had no difference between vasodepressor type and mixed type; however,
      syncopal episode had a significant difference between children aged <=12 and >12
      years (chi (2) = 6.371, P < 0.05); there was no difference in reperformed HUTT
      response. ORS with 500 ml of water is an effective therapy for VVS. It can be
      recommended as one of non- pharmacological treatment measures in children with
      VVS.

PMID- 25577228
TI  - Cardiac catheterization in children with pulmonary hypertensive vascular disease.
AB  - The risks associated with cardiac catheterization in children with pulmonary
      hypertension (PH) are increased compared with adults. We reviewed retrospectively
      all clinical data in children with PH [mean pulmonary artery pressure (mean PAp)
      >=25 mmHg and pulmonary vascular resistance index (PVRI) >=3 Wood units m(2)]
      undergoing cardiac catheterization between 2009 and 2014. Our strategy included a
      team approach, minimal catheter manipulation and sildenafil administration prior
      to extubation. Adverse events occurring within 48 h were noted. Seventy-five
      patients (36 males), median age 4 years (0.3-17) and median weight 14.6 kg (2.6
      77 kg), underwent 97 cardiac catheterizations. Diagnoses included idiopathic or
      heritable pulmonary arterial hypertension (PAH) (29 %), PAH associated with
      congenital heart disease (52 %), left heart disease (5 %) and lung disease (14
      %). Mean PAp was 43 +/- 19 mmHg; mean PVRI was 9.7 +/- 6 Wood units m(2). There
      were no deaths or serious arrhythmias. No patient required cardiac massage. Three
      patients who suffered adverse events had suprasystemic PAp (3/3), heritable PAH
      (2/3), decreased right ventricular function (3/3), and pulmonary artery
      capacitance index <1 ml/mmHg/m(2) (3/3) and were treatment naive (3/3). No
      patient undergoing follow-up cardiac catheterization suffered a complication. In
      45 % of cases, the data acquired from the follow-up cardiac catheterization
      resulted in an alteration of therapy. Three percent of children with PH
      undergoing cardiac catheterization suffered adverse events. However, there were
      no intra or post procedural deaths and no one required cardiac massage or
      cardioversion. Follow-up cardiac catheterization in patients receiving pulmonary
      hypertensive targeted therapy is safe and provides useful information.

PMID- 25577230
TI  - Nitric oxide participates in the regulation of the ascorbate-glutathione cycle by
      exogenous jasmonic acid in the leaves of wheat seedlings under drought stress.
AB  - In this paper, we investigated whether nitric oxide (NO) participated in the
      regulation of the ascorbate-glutathione (AsA-GSH) cycle by exogenous jasmonic
      acid (JA) in the leaves of wheat seedlings under drought stress. The findings of
      our study showed that drought stress significantly enhanced the AsA-GSH cycle by
      upregulating the activities of ascorbate peroxidase (APX), glutathione reductase
      (GR), monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase
      (DHAR). Drought stress also markedly increased electrolyte leakage (EL),
      malondialdehyde (MDA) content, NO content, and significantly reduced the ratios
      of reduced ascorbate/dehydroascorbic acid (AsA/DHA) and reduced
      glutathione/oxidized glutathione (GSH/GSSG) compared with control. Exogenous JA
      significantly increased the above indicators, compared with drought stress alone.
      All these effects of JA were inhibited by pretreatment with NO scavenger 2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). Meanwhile,
      exogenous JA markedly decreased MDA content and electrolyte leakage of wheat
      leaves under drought stress. Pretreatment with cPTIO reversed the above effects
      of exogenous JA. Our findings indicated that NO induced by exogenous JA
      upregulated the activity of the AsA-GSH cycle and had important role in drought
      tolerance.

PMID- 25577229
TI  - An Ethical Issue Scale for Community Pharmacy Setting (EISP): Development and
      Validation.
AB  - Many problems that arise when providing pharmacy services may contain some
      ethical components and the aims of this study were to develop and validate a
      scale that could assess difficulties of ethical issues, as well as the frequency
      of those occurrences in everyday practice of community pharmacists. Development
      and validation of the scale was conducted in three phases: (1) generating items
      for the initial survey instrument after qualitative analysis; (2) defining the
      design and format of the instrument; (3) validation of the instrument. The
      constructed Ethical Issue scale for community pharmacy setting has two parts
      containing the same 16 items for assessing the difficulty and frequency thereof.
      The results of the 171 completely filled out scales were analyzed (response rate
      74.89%). The Cronbach's alpha value of the part of the instrument that examines
      difficulties of the ethical situations was 0.83 and for the part of the
      instrument that examined frequency of the ethical situations was 0.84. Test
      retest reliability for both parts of the instrument was satisfactory with all
      Interclass correlation coefficient (ICC) values above 0.6, (for the part that
      examines severity ICC = 0.809, for the part that examines frequency ICC = 0.929).
      The 16-item scale, as a self assessment tool, demonstrated a high degree of
      content, criterion, and construct validity and test-retest reliability. The
      results support its use as a research tool to asses difficulty and frequency of
      ethical issues in community pharmacy setting. The validated scale needs to be
      further employed on a larger sample of pharmacists.

PMID- 25577231
TI  - Increased risks of healthcare-seeking behaviors of anxiety, depression and
      insomnia among patients with bladder pain syndrome/interstitial cystitis: a
      nationwide population-based study.
AB  - PURPOSE: To explore the association between bladder pain syndrome/interstitial
      cystitis (BPS/IC) and the risk of subsequent healthcare-seeking behavior for
      common mental disorders in Taiwan using a population-based administrative
      database. MATERIALS AND METHODS: Both BPS/IC subjects and their age- and sex
      matched non-BPS/IC control subjects who had no previous insomnia and mental
      diseases, including anxiety, depression, were subsequent serviced for these
      mental disorders by psychiatrists from the recruited date between 2002 and 2010.
      The risk of outcomes was assessed with Kaplan-Meier curves; and the impact of
      BPS/IC was estimated with Poisson regression analysis and Cox proportional
      hazards models. RESULTS: We included 16,185 BPS/IC subjects and 32,370 non-BPS/IC
      subjects, with a mean age of 46 years and 73.5 % of women. Difference of the
      prevalence of hypertension, diabetes, chronic kidney disease, and hyperlipidemia
      between groups was not significant difference. Subjects with BPS/IC had a
      significant higher incidence rate of anxiety, depression, and insomnia than the
      matched controls (92.9 vs 38.4, 101.0 vs 42.2, 47.5 vs 23.0; per 10,000 person
      year). After adjusting for age, sex, and common comorbidities in multivariable
      analysis, BPS/IC remained a significant predictor with hazard ratio and 95 %
      confidence incidence, 2.4 (2.2-2.7), 2.4 (2.2-2.6), and 2.1 (1.8-2.4) for
      anxiety, depression, and insomnia, respectively. CONCLUSION: Patients with BPS/IC
      are at risk of development of anxiety, depression, and insomnia. These findings
      can help guide urologists, urogynecologists, and psychiatrists toward early
      identification and treatment of psychological complications that may develop in
      BPS/IC patients.

PMID- 25577232
TI  - Concurrent arm swing-stepping (CASS) can reveal gait start hesitation in
      Parkinson's patients with low self-efficacy and fear of falling.
AB  - BACKGROUND: Movement incoordination, freezing of gait, fear of falling, low self
      efficacy, and multi-tasking can all contribute to falls in Parkinson's disease.
      How these multi-factorial risks interact in individual patients remain poorly
      understood. METHODS: Concurrent arm swing-stepping is a simple motor test in
      which subjects are first asked to swing their arms before being instructed to
      initiate the secondary task of leg stepping-in-place. We postulated that in
      patients with multiple fall risks, sensorimotor impairments in upper- and lower
      limb movement control can render concurrent arm swing-stepping a demanding dual
      task, thereby triggering gait hesitation. A total of 31 subjects with Parkinson's
      disease were enrolled in the study. RESULTS: It was found that concurrent arm
      swing-stepping induced hesitation primarily in Parkinson's disease patients with
      low fall-related self-efficacy and a fear of falling. By contrast, concurrent arm
      swing-stepping led to limb incoordination in both patients and in healthy elderly
      controls. The calculated specificity and sensitivity of the concurrent arm swing
      stepping test was 100 and 42 % for hesitation and 12 and 77 % for incoordination.
      CONCLUSION: These results suggest that the concurrent arm swing-stepping test can
      be used in conjunction with conventional psychometric assessments to facilitate
      multi-factorial assessment of potential fall risk.

PMID- 25577233
TI  - Aliased noise in X-ray CT images and band-limiting processing as a preventive
      measure.
AB  - X-ray CT projection data often include components with frequencies that are
      markedly higher than the pixel Nyquist frequency f PN, which is determined by the
      pixel size. Noise components higher than f PN are folded back into a region lower
      than f PN through the backprojection process, thereby creating aliased noise.
      With clinical CT scanners, we evaluated the aliased noise using an aliasing
      prevention measure, band-limiting processing (BLP), which suppresses frequency
      components higher than f PN in the projection data. Indices we used to evaluate
      improvement by BLP were the noise power spectrum (NPS), modulation transfer
      function (MTF), signal-to-noise-ratio (SNR) spectrum, matched filter SNR (MF
      SNR), and two-alternative forced-choice (2-AFC) test. With BLP, the NPS was
      decreased not only beyond f PN, but also within f PN. The same level of MTF was
      maintained as that without BLP within f PN. No remarkable reduction in spatial
      resolution was observed. The SNR spectrum and the MF SNR of the BLP image nearly
      agreed with those of an ideal state without aliased noise. A notable improvement
      in the visuoperceptual image quality by BLP was recognized with a reconstruction
      field of view (FOV) of more than 45 cm. We then applied BLP to clinical data and
      confirmed that significant aliased noise of a large FOV image was removed without
      notable side effects. The results showed that at least some CTs suffering from
      aliased noise can be improved by proper band-limiting. 

PMID- 25577234
TI  - Fat-subtracted three-dimensional time-of-flight MR angiography of the neck by use
      of fat-only images with the two-point Dixon technique.
AB  - For improvement of three-dimensional time-of-flight magnetic resonance
      angiography (3D-TOF-MRA) image quality in the neck, fat-subtracted MRA by use of
      the two-point Dixon technique was compared with conventional fat-suppressed MRA
      techniques. Three different types of neck 3D-TOF-MRA were obtained [minimum echo
      time (TE) (1.9 ms), opposed-phase TE (3.4 ms), and chemical shift selective fat
      suppression (CHESS) (TE = 1.9 ms)] on five volunteers at 3.0 T. MRA was obtained
      with subtraction of fat-only images (produced by a two-point Dixon sequence) from
      minimum-TE MRA images, and compared with other fat-suppressed MRA images. Fat
      subtracted MRA demonstrated uniform fat suppression compared with other
      techniques. The mean vessel-to-fat contrast in fat-subtracted MRA was
      significantly higher (p < 0.01) than in other MRA images (minimum-TE: 0.137 +/-
      0.086, opposed-phase TE: 0.268 +/- 0.102, CHESS: 0.307 +/- 0.052, fat-subtracted:
      0.965 +/- 0.101). The mean vessel-to-muscle contrast in opposed-phase TE MRA was
      significantly lower (p < 0.01) than in other MRA images (minimum-TE: 0.526 +/-
      0.036, opposed-phase TE: 0.419 +/- 0.188, CHESS: 0.511 +/- 0.023, fat-subtracted:
      0.573 +/- 0.016). Fat-subtracted MRA by use of the two-point Dixon technique
      improves the image quality of neck MRA. This technique would be a useful method
      for MRA, especially in areas with inhomogeneous magnetic fields, such as the
      neck. 

PMID- 25577235
TI  - A methylation-specific dot blot assay for improving specificity and sensitivity
      of methylation-specific PCR on DNA methylation analysis.
AB  - BACKGROUND AND OBJECTIVES: Developing a methylation-specific dot blot assay (MSP
      DB) to increase the sensitivity and specificity of simultaneous methylation
      analysis of multiple genes is the goal of the present study to evaluate the
      methylation status of GSTP1 and RASSF1A from prostate cancer in Vietnamese males.
      METHODS: The methylation of GSTP1 and RASSF1A was investigated by using the MSP
      in 50 prostate cancer and 17 benign prostate hyperplasia specimens. The MSP-DB
      assay that uses a single or multiple probes specifically detected the methylation
      status of a particular gene or of the two genes GSTP1 and RASSF1A at the same
      time in a series of samples. The sensitivity and specificity of the MSP-DB were
      compared to those of the MSP. RESULTS: The probes specifically hybridized with
      the methylated targets only in the MSP-DB, which allowed detecting GSTP1 and
      RASSF1A methylation in 23 of 50 and 14 of 50 patients with prostate cancer and in
      2 of 17 and 4 of 17 patients with benign prostate hyperplasia. MSP-DB following
      the MSP assay improved the sensitivity of detection to more than 0.01 %
      methylated status of a given high CpG-rich region. One methylated MSP product
      corresponding to the GSTP1, lack of methylated cytosine, was clearly detected on
      gel electrophoresis but barely visible on MSP-DB. Thus, the MSP-DB is suitable to
      eliminate the risk of false-positive results. CONCLUSION: The MSP-DB dispels the
      weakness of MSP and increases the sensitivity to simultaneous methylation
      analysis of multiple genes. The MSP-DB is advantageous for the promotion of DNA
      methylation markers in progressing quickly toward clinical application.

PMID- 25577236
TI  - The methyl donor S-adenosylmethionine potentiates doxorubicin effects on
      apoptosis of hormone-dependent breast cancer cell lines.
AB  - In this work, we have investigated the antiproliferative effect of AdoMet and
      Doxorubicin (Doxo), alone or in combination, on different breast cancer cell
      lines. For the evaluation of synergism, we have calculated the combination index
      (CI) by the Calcusyn software and we have evaluated the effects of the
      combination on apoptosis occurrence at FACS analysis in hormone-dependent CG5
      cell line. We have found that AdoMet and Doxo given in combination were strongly
      synergistic in the hormone-dependent CG5 and MCF-7 human breast cancer cell line,
      as a CI50 < 0.5 was found after 72 h of treatment while the effect was only
      additive in hormone-independent MDA-MB 231 cells. On the basis of our results, we
      have selected a combination of AdoMet and Doxo, that was highly synergistic and
      we have found that the AdoMet in combination with Doxo increased apoptosis
      induced by Doxo alone, suggesting that the synergism on growth inhibition was
      largely due to apoptosis. Notably, the AdoMet/Doxo combination induced a
      significant activation of caspases 3, and 8, while no effect was found on caspase
      9 cleavage. In contrast, no significant changes of the expression of cleaved
      caspase 8 and 9 were found in cells treated with AdoMet and Doxo alone. Moreover,
      the combination induced a significant increase of Fas and FasL expression. These
      results highlight the importance of the synergistic effect of AdoMet with Doxo in
      the regulation of hormone-dependent breast cancer cell proliferation and
      emphasize the anti-tumor activity of these molecules.

PMID- 25577237
TI  - Role of homocysteine in the development of cardiovascular disease.
AB  - It is well known that neuronal damage following a stroke has been attributed to
      the over stimulation of excitatory amino acids such as glutamate and aspartate
      through activation of NMDA receptors. The brain is exposed to most of the
      constituents of plasma including homocysteine as a result of the disruption of
      the blood-brain barrier after stroke, head trauma and stress. The question,
      therefore, arises as to whether or not homocysteine is able to selectively
      stimulate the release of excitatory amino acids in stroke. This review article
      will address the importance of homocysteine in nervous system specifically how
      these amino acids may trigger the release of catecholamines. Our data will thus
      strengthen the view that a mechanism for the association of hyperhomocysteinemia
      with increased brain lesion in stroke. As hypothalamus also controls the cardiac
      function via sympathetic system, the contractility of heart will be compromised.
      Homocysteine is also known to mediate cardiovascular problems by its adverse
      effects on cardiovascular endothelium and smooth muscle cells with resultant
      alterations in subclinical arterial structure and function. The present review
      will thus summarize both central and peripheral effects of homocysteine and will
      highlight some of the controversies associated with hyperhomocysteinemia-induced
      cardiovascular problems. 

PMID- 25577238
TI  - Relationships of Shared Decision Making with Parental Perceptions of Child Mental
      Health Functioning and Care.
AB  - Experts encourage parents and practitioners to engage in shared decision making
      (SDM) to provide high quality child mental health care. However, little is known
      regarding SDM among families of children with common mental health conditions.
      The objectives of this study were to examine associations between parental report
      of SDM and parental perceptions of (a) receiving child mental health care and (b)
      child mental health functioning. We analyzed cross-sectional data on children
      with a common mental health condition (attention-deficit hyperactivity disorder,
      oppositional-defiant or conduct disorder, anxiety, or depression) from the
      2009/2010 National Survey of Children with Special Healthcare Needs (N = 9,434).
      The primary independent variable was parent-reported SDM, and the dependent
      variables were parental perception of (a) their child receiving all needed mental
      health care (b) their children's impairment in school attendance and
      extracurricular activity participation, and (c) severity of their children's
      mental health condition. Multivariate logistic and multinomial regression
      analyses were conducted. Greater parent-reported SDM was associated with parental
      perceptions of receiving all needed child mental health care and children not
      having school or extracurricular impairment. Greater SDM was also associated with
      perceptions of children having a mild mental health condition compared to
      children having a moderate or severe condition. Findings provide a basis for
      future longitudinal and intervention studies to examine the benefit of SDM for
      improving parental perceptions of the quality of child mental health care and
      mental health functioning among children with common mental health conditions.

PMID- 25577239
TI  - Participating in a world that is out of tune: shadowing an older hospital
      patient.
AB  - Hospitalization significantly impacts the lives of older people, both physically
      and psychosocially. There is lack of observation studies that may provide an
      embodied understanding of older patients' experiences in its context. The aim of
      this single case study was to reach a deeper understanding of one older patient's
      lived experiences of hospitalization. The study followed a phenomenological
      embodied enquiry design and the qualitative observation method of shadowing was
      used. In April 2011, one older patient was shadowed for 7 days, 5-7 h per day. To
      facilitate understanding in the reader the experiences are first presented in a
      story and subsequently analyzed by means of the lifeworld framework. The findings
      show that hospitalization is experienced as ambiguous safety, disconnected time,
      the feeling of being partially involved, and the struggle to re-attune to the
      body.

PMID- 25577240
TI  - Does rotational acetabular osteotomy affect subsequent total hip arthroplasty?
AB  - INTRODUCTION: Rotational acetabular osteotomy (RAO) has been used successfully in
      patients with developmental dysplasia of the hip (DDH). However, some patients
      are forced to undergo total hip arthroplasty (THA) because of the progression of
      osteoarthritis. We evaluated the effect of previous RAO on the outcome of THA
      performed for degenerative arthritis secondary to DDH, comparing outcomes for
      patients with THA and prior RAO versus outcomes for patients with THA and no
      prior RAO. MATERIALS AND METHODS: At an average follow-up point of 8.2 years
      (range 7-11 years), we compared outcomes in dysplastic hips for 22 hips (group R)
      in patients who underwent THA after successful RAO with outcomes for a well
      matched control group of 30 hips in patients who underwent primary THA (group C)
      during the same period. RESULTS: Both groups had similar midterm results. No
      acetabular or femoral components exhibited loosening or revision in either group.
      Harris hip scores (HHSs) at the most recent follow-up had not been compromised by
      RAO, and there were no significant differences in intraoperative blood loss and
      operative time between the two groups. Although there was a tendency toward
      superolateral placement of the acetabular component in group R, there were no
      significant differences in the mean steady-state linear and volumetric wear rates
      between the two groups. There were no infections, dislocations, intraoperative
      fractures, damaged nerves, or deep vein thromboses in either group. CONCLUSIONS:
      Our midterm results demonstrated that RAO does not lead to higher revision rates,
      compromised HHSs, or shortened survivorship in eventual THA for DDH.

PMID- 25577241
TI  - Plate fixation of extra-articular fractures of the proximal phalanx: do new
      implants cause less problems?
AB  - BACKGROUND: Limited range of finger motion is a frequent complication after plate
      fixation of phalangeal fractures. The purpose of this study was to evaluate the
      results of plate fixation of extra-articular fractures of the proximal phalanx
      using current low-profile mini-fragment-systems. METHODS: From 2006 to 2012, 32
      patients with 36 extra-articular fractures of the proximal phalanx of the
      triphalangeal fingers were treated with open reduction and plate fixation (ORPF)
      using 1.2 and 1.5 mm mini-fragment systems. Patients presenting with open
      fractures grade 2 and 3 or relevant laceration of adjacent structures were
      excluded from the study. We retrospectively evaluated the rate of mal-union or
      non-union after ORPF, the need for revision surgery, for plate removal, and for
      tenolysis. Data were analyzed for further complications with regard to infections
      or complex regional pain syndrome (CRPS). RESULTS: No infections were noted. Five
      patients developed transient symptoms of CRPS. Six weeks postoperatively, total
      active finger motion (TAM) averaged 183 degrees , and all 32 patients underwent
      formal hand therapy. At the latest follow-up or at the time of plate removal,
      respectively, the mean TAM improved to 213 degrees . Extension lag of proximal
      interphalangeal joints was found in 67 % of all fractured fingers. Secondary
      surgery was necessary in 14 of 32 patients (2 corrective osteotomies, 12 plate
      removals including 7 procedures explicitly because of reduced mobility).
      CONCLUSIONS: Despite of new implant designs significant problems persist.
      Adhesions of extensor tendons leading to limited range of finger motion are still
      the most frequent complications after ORPF of proximal phalangeal fractures, even
      in absence of significant soft-tissue damage. LEVEL OF EVIDENCE: Therapeutic,
      Retrospective, Level IV.

PMID- 25577242
TI  - Easy and unambiguous sequential assignments of intrinsically disordered proteins
      by correlating the backbone 15N or 13C' chemical shifts of multiple contiguous
      residues in highly resolved 3D spectra.
AB  - Sequential resonance assignment strategies are typically based on matching one or
      two chemical shifts of adjacent residues. However, resonance overlap often leads
      to ambiguity in resonance assignments in particular for intrinsically disordered
      proteins. We investigated the potential of establishing connectivity through the
      three-bond couplings between sequentially adjoining backbone carbonyl carbon
      nuclei, combined with semi-constant time chemical shift evolution, for resonance
      assignments of small folded and larger unfolded proteins. Extended sequential
      connectivity strongly lifts chemical shift degeneracy of the backbone nuclei in
      disordered proteins. We show here that 3D (H)N(COCO)NH and (HN)CO(CO)NH
      experiments with relaxation-optimized multiple pulse mixing correlate up to seven
      adjacent backbone amide nitrogen or carbonyl carbon nuclei, respectively, and
      connections across proline residues are also obtained straightforwardly.
      Multiple, recurrent long-range correlations with ultra-high resolution allow
      backbone (1)H(N), (15)N(H), and (13)C' resonance assignments to be completed from
      a single pair of 3D experiments. 

PMID- 25577243
TI  - Silencing of activin receptor-like kinase 7 alleviates aortic stiffness in type 2
      diabetic rats.
AB  - AIM: Arterial stiffness is an important feature of diabetic macrovascular
      complications. Activin receptor-like kinase 7 (ALK7), a member of type I
      transforming growth factor-beta (TGF-beta) receptors, is correlated with
      pathogenic risks of type 2 diabetes mellitus and cardiovascular diseases and may
      be involved in cardiovascular remodeling. We aimed to investigate whether ALK7 is
      implicated in diabetes-induced aortic stiffness. METHODS: Type 2 diabetes was
      induced by high-fat diet and low-dose streptozotocin (STZ; 27.5 mg/kg). Forty
      rats were separated into four groups: control, diabetes, diabetes with empty
      virus and diabetes treated with ALK7-shRNA. The metabolic index, ALK 7 expression
      and aortic stiffness were evaluated. We used gene silencing method to investigate
      the role of ALK7 in the pathological development. RESULTS: Diabetic rats showed
      increased blood glucose, cholesterol, triglyceride levels, severe insulin
      resistance and ALK7 overexpression. Diabetes enhanced aortic stiffness, as
      demonstrated by the loss and disruption of elastic fibers as well as by an
      increase in collagen fibers in the aortic media. ALK7 gene silencing ameliorated
      metabolic hyperlipidemia and insulin resistance. With ALK7 gene silencing,
      collagen content, elastin to collagen ratio, as well as collagen I-to-collagen
      III content ratio in diabetic rats were significantly decreased. Moreover, the
      phosphorylation level of Smad2/3 was markedly decreased after ALK7 gene
      silencing. CONCLUSIONS: ALK7 gene silencing has a protective effect on diabetes
      induced aortic stiffness, insulin resistance and hyperlipidemia, thus implicating
      a new potential therapeutic approach to diabetic macrovascular stiffness.

PMID- 25577244
TI  - Short-term effects of glucagon-like peptide 1 (GLP-1) receptor agonists on fat
      distribution in patients with type 2 diabetes mellitus: an ultrasonography study.
AB  - AIMS: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) induce weight loss and
      reduction in adipose tissue, but the effects of GLP-1 RA on the distribution of
      fat deposits have been poorly investigated. METHODS: In 25 patients with type 2
      diabetes (16 females and 9 males, mean age 63.5 +/- 8.8 years), treated with GLP
      1 RA (exenatide, n. 12; liraglutide, n.13), both before and 3 months after
      starting treatment, an abdominal ultrasonographic scan, with Doppler of renal
      arteries, and echocardiography were performed. Subcutaneous fat width (peri
      umbilical and sub-xiphoid), deep fat deposits (pre-aortic, peri-renal, and
      epicardial), and renal resistive index (RI) were evaluated. RESULTS: GLP-1 RA
      induced highly significant (p < 0.001) decrease in BMI and in fat thickness at
      all the assessed sites, without differences between exenatide and liraglutide
      treatment. A slight decrease in RI (p = 0.055) was also found. The percent
      changes of fat thickness was different between sites (p < 0.025), and the changes
      in subcutaneous deposits showed no significant correlation (p = 0.064) with those
      of deep fat deposits. CONCLUSIONS: A short course of treatment with GLP-1 RA,
      besides weight loss, induces a redistribution of adipose tissue deposits,
      possibly contributing to a better cardiovascular risk profile in patients with
      type 2 diabetes mellitus.

PMID- 25577245
TI  - Involvement of NEDD9 in the invasion and migration of gastric cancer.
AB  - Recent studies have demonstrated that neural precursor cell expressed,
      developmentally downregulated 9 (NEDD9) is highly expressed in various tumor
      tissues and cell lines. However, research on the role of NEDD9 in gastric cancer
      (GC) is rare, and the potential mechanism in tumor progression has not yet been
      explored. In this study, we investigated the role and mechanism of NEDD9 in GC.
      The expression of NEDD9 in GC tissues and cell lines was measured by
      immunohistochemistry, qRT-PCR, and Western blot, respectively. Inhibiting NEDD9
      expression was carried out by siRNA transfection, and upregulating of NEDD9 was
      via NEDD9 overexpression plasmid. The ability of proliferation, migration, and
      invasion was detected by MTT assay, scratch wound assay, and transwell assay,
      respectively. The expression of vimentin, E-cadherin, Zeb1, and Zeb2 was measured
      by Western blot and qRT-PCR. We found that NEDD9 expression was dramatically
      increased both in GC tissues and cell lines, and the expression was significantly
      related to GC development. Knockdown of NEDD9 in SGC-7901 strongly inhibited its
      malignant capacity in vitro. Meanwhile, upregulation of NEDD9 in GES-1 increased
      the malignant capacity. In addition, the expression of vimentin, Zeb1, and Zeb2
      was positively correlated with NEDD9, while E-cadherin was opposite.
      Collectively, our findings suggest that NEDD9 acts as an oncogene and promotes GC
      metastasis via EMT. 

PMID- 25577246
TI  - Overexpression of VEGF183 promotes murine breast cancer cell proliferation in
      vitro and induces dilated intratumoral microvessels.
AB  - Vascular endothelial growth factor (VEGF) was considered as a critical growth
      factor for tumor expansion. The roles of VEGF121, VEGF165, and VEGF189 in tumor
      growth have been intensely investigated; however, involvements of another
      extracellular matrix (ECM)-binding VEGF isoform, namely VEGF183 (six amino acids
      shorter than VEGF189 in exon 6a), in physiological or pathological processes are
      still unclear although the wide tissue distribution. To investigate the role of
      VEGF183 in carcinogenesis, we generated murine breast cancer cell (EMT-6) clones
      stably overexpressing VEGF183, VEGF121, VEGF165, and VEGF189 shortened as V183,
      V121, V165, and V189, respectively. Methylthiazolyldiphenyl-tetrazolium bromide
      (MTT) results showed that VEGF183, like all other VEGF-overexpressing isoforms
      except for VEGF121, could enhance the proliferation of mouse breast cancer EMT-6
      cells. Immunochemistry results displayed that overexpressing VEGF183 and VEGF189
      in EMT-6 cells induced larger proportional dilated microvessels. On the other
      hand, results from cell wound healing experiments demonstrated that all of the
      VEGF-overexpressing isoforms could increase the chemotaxis of EMT-6 cells in
      vitro. In conclusion, our results supported the idea that overexpression of
      VEGF183 promotes murine breast cancer cell proliferation in vitro and induces
      dilated intratumoral microvessels, and it plays a dissimilar role in comparison
      with that of VEGF189. 

PMID- 25577247
TI  - Arginase-1 is a more sensitive marker than HepPar-1 and AFP in differential
      diagnosis of hepatocellular carcinoma from nonhepatocellular carcinoma.
AB  - Distinguishing hepatocellular carcinoma (HCC) from metastatic tumors is a
      challenging issue, especially in differential diagnosis between poorly
      differentiated HCC and metastasis tumors. Expression of Arg-1, HepPar-1, and
      alpha-fetoprotein (AFP) in 78 cases of HCC, 34 cases of metastatic tumors, and
      228 cases of nonhepatocellular tumors of surgical specimens is measured by
      immunohistochemistry. Arg-1 immunoreactivity was detected in 75 of 78 (96.1 %)
      cases of HCC, whereas HepPar-1 and AFP immunoreactivity was detected in 63 of 78
      (80.7 %) and 40 of 78 (51.3 %) cases of HCC, respectively. HepPar-1 and AFP
      expression was observed in three of 34 (8.8 %) cases and one of 34 (2.9 %) cases
      of metastatic tumors, respectively. In contrast, Arg-1 expression was absent in
      all 34 (0 %) cases of metastatic tumors. The sensitivity, specificity, positive
      predictive value, and negative predictive value of Arg-1 in distinguishing HCC
      from metastatic tumors and nonhepatocellular tumors are 96.1, 99.6, 98.7, and
      98.8 % compared with 80.7, 92.0, 75.0, and 94.1 % for HepPar-1 and 51.3, 97.7,
      87.0, and 87.1 % for AFP, respectively. Arg-1 is a more sensitive and better
      specific marker for HCC compared with HepPar-1 and AFP, indicating that Arg-1 can
      be easily applied in distinguishing HCC from metastatic tumors.

PMID- 25577248
TI  - Identification of cystatin SN as a novel biomarker for pancreatic cancer.
AB  - Cystatin SN (cystatin 1, CST1) is a member of the cystatin superfamily that
      inhibits the proteolytic activity of cysteine proteases. CST1 is a tumor
      biomarker that provides useful information for the diagnosis of esophageal,
      gastric, and colorectal carcinomas. However, the significance of CST1 in
      pancreatic cancer is unknown. The aim of this study was to assess whether CST1 is
      a potential biomarker for early diagnosis of malignant pancreatic neoplasms.
      Microarray analysis of mRNA extracted from pancreatic cancer and pancreatic
      normal tissues was performed. Bioinformatics revealed that CST1 was one of the
      highest expressed genes on the array in pancreatic cancer, compared with normal
      tissue. In addition, the upregulation of CST1 in pancreatic cancer and several
      pancreatic cancer cell lines was confirmed using real-time PCR (RT-PCR),
      immunohistochemistry, and Western blotting. Next, CST1 knockdown using siRNA
      reduced the expression of the proliferation-related proteins p-AKT and PCNA
      significantly, as well as colony formation and xenograft development in vitro.
      Consistent with this, CST1 mRNA overexpression was correlated closely with
      malignancy-associated proteins such as PCNA, cyclin D1, cyclin A2, and cyclin E
      in pancreatic cancer cell lines. In conclusion, our data suggest that CST1 might
      contribute to the proliferation of pancreatic cancer cells and could be a
      potential biomarker for the early detection of pancreatic cancer. 

PMID- 25577249
TI  - microRNA-377 suppresses the proliferation of human osteosarcoma MG-63 cells by
      targeting CDK6.
AB  - MicroRNAs (miRNAs) are essential to the progression of osteosarcoma. Previous
      research using osteosarcoma samples confirmed that miR-377 expression is less
      than that observed in normal human osteoblast expression. These data suggest a
      role for miR-377 in osteosarcoma that warrants investigation. To address this
      concept, we measured miR-377 expression in two cell models, and we also observed
      that miR-377 was less expressed in osteosarcoma MG-63 cells compared to the
      hFOB1.19 human fetal osteoblastic cell line. Moreover, miR-377 overexpression
      reduced cell proliferation and suppressed invasion of MG-63 cells but had no
      effect on MG-63 cell apoptosis. Because cyclin-dependent kinase 6 (CDK6) may be a
      potential target of miR-377 in osteosarcoma cells, we overexpressed CDK6 and
      observed that overexpression attenuated tumor suppressive effects of miR-377 on
      cell proliferation. Our data suggest that miR-377 can suppress proliferation in
      MG-63 cells in part by targeting CDK6. 

PMID- 25577250
TI  - Arsenic trioxide inhibits growth of human chondrosarcoma cells through G2/M
      arrest and apoptosis as well as autophagy.
AB  - It has been demonstrated that Gli1 is expressed in chondrosarcoma but not in the
      normal articular cartilage tissues. Downregulating Gli1 by small interfering RNA
      inhibited chondrosarcoma cells growth. Arsenic trioxide (ATO) has been
      demonstrated to suppress human cancer cell growth by targeting Gli1. The aim of
      this study was to investigate the effect of ATO on antineoplastic capability of
      chondrosarcoma cells. We found that ATO inhibited the growth of chondrosarcoma
      cells in dose-dependent and time-dependent manners via MTT and colony formation
      assays. In addition, ATO treatment induced apoptosis and promoted G2/M phase
      arrest in SW1353 cells as analyzed by flow cytometry assays and Western blotting.
      Furthermore, we observed that ATO also triggered autophagy by regulating
      mammalian target of rapamycin (mTOR) phosphorylation. Finally, we found that ATO
      mediated cell death could be averted by autophagy inhibitor. Taken together, the
      current study suggested that ATO had therapeutic efficacy in human chondrosarcoma
      cells through the promotion of G2/M arrest and induction of both apoptosis as
      well as autophagy. ATO administration could be a novel therapeutic strategy for
      treating chondrosarcomas.

PMID- 25577251
TI  - Association between the genetic variations within TBX21 gene promoter and the
      clinicopathological characteristics of esophageal squamous cell carcinoma in a
      high-risk Chinese population.
AB  - The correlation between TBX21 gene (T-box transcription factor protein 21; T
      bet), which was a pivotal transcriptional regulation gene for Th1/Th2
      polarization, and the development risk of esophagus squamous cell carcinoma
      (ESCC) was assessed in a high-risk Chinese population. A total of 302 ESCC cases
      and 311 normal controls coming from the highest incidence area of China were
      enrolled in this study. Three polymorphisms at -1499, -1514, and -1993 located in
      the TBX21 promoter were identified by the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method. Logistic regression was used to
      determine whether the inherited variations of the TBX21 gene would associate with
      the risk and the clinicopathological characteristics of ESCC. Among the ESCC
      patients, an association between the TBX21 -1514T/C or -1993T/C polymorphisms and
      the lymph node or distant metastasis was found (odds ratios (ORs) were 9.46 and
      4.35, respectively, all P < 0.01). By the log-additive model analysis, the
      results exhibited that three haplotypes, ACC, ACT, and ATC, were significantly
      related to the development risk of ESCC (OR = 11.81, 3.44, 2.37, respectively,
      all P < 0.05). TBX21 gene -1514 and -1993 polymorphisms might be counted as the
      influential factors for lymph node and distant metastasis to ESCC. Especially,
      the ACC, ACT, and ATC haplotypes derived from the TBX21 gene would increase the
      susceptibility to ESCC in the high-risk Chinese population.

PMID- 25577252
TI  - Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single
      center controlled study.
AB  - This study aims to investigate the correlation between preoperative human
      epididymis protein 4 (HE4) levels, endometrial cancer (EC) staging, and ideal
      cutoff for stage prediction. All EC patients, treated within January 2009 and
      February 2014 at the Division of Gynaecologic Oncology of the University Campus
      Bio-Medico of Rome, were considered for the study. For the first part of the
      study, we consider an HE4 cutoff of 70 pmol/L. Histotypes (endometrioid versus
      non-endometrioid), grading (G1, G2, G3), and stage were correlated with HE4
      levels. In the second part of the study, the logistic regression was performed in
      stepwise mood to identify the ideal HE4 cutoff for stage prediction. Two hundred
      thirty-two patients with surgically staged EC and preoperative HE4 dosage were
      included in the study. We found that higher HE4 levels correlate with
      undifferentiated grading (p < 0.05). Moreover, we found that 42, 77, 90, 93 and
      100 % of patients classified as International Federation of Gynecology and
      Obstetrics (FIGO) stage IA, IB, II, III, and IV, respectively, presented HE4
      levels above the standard cutoff of 70 pmol/L. Based on receiver operating
      characteristic (ROC) curves, we found the ideal HE4 cutoff as follows: 61.3
      pmol/L for FIGO stage IA (sensitivity = 82.3 % and specificity = 96 %), 89.2
      pmol/L for FIGO stage IB (sensitivity = 83.3 % and specificity = 96 %), 104.3
      pmol/L for FIGO stage II (sensitivity = 80.9 % and specificity = 98.6 %), 152.6
      pmol/L for FIGO stage III (sensitivity = 92.5 % and specificity = 98.6 %), and
      203.8 pmol/L for FIGO stage IV (sensitivity = 81.8 % and specificity = 99.3 %).
      Our results suggest a potential role of HE4 in EC stage prediction.

PMID- 25577253
TI  - Prognostic significance of pretreatment VEGF, survivin, and Smac/DIABLO serum
      levels in patients with serous ovarian carcinoma.
AB  - The second mitochondria-derived activator of caspase (Smac/DIABLO), vascular
      endothelial growth factor (VEGF), and survivin are known to play a significant
      role in the growth and development of numerous tumors. Serum concentrations of
      VEGF, survivin, and Smac/DIABLO were analyzed in 92 patients with serous ovarian
      cancer and 94 healthy controls. Values were correlated with clinicopathological
      characteristics and outcomes. The median pretreatment serum VEGF and survivin
      levels in patients with serous ovarian carcinoma were significantly higher, while
      Smac/DIABLO levels were significantly lower than that in healthy controls.
      Receiver operating characteristic (ROC) curve analysis showed that the best
      cutoff point for VEGF was determined to be 345 pg/ml; with 83 % sensitivity and
      65 % specificity. For survivin, the cutoff point was 110 pg/ml and for
      Smac/DIABLO was 75 pg/ml, with 82 and 62 % sensitivity and 43 and 87 %
      specificity, respectively. In the patients group, higher VEGF and survivin levels
      and lower Smac/DIABLO levels in sera were significantly associated with poorer
      overall survival (OS) and disease-free survival (DFS). Preoperative measurement
      of serum VEGF, survivin, and Smac/DIABLO may be of help in early detection of
      serous ovarian cancer and may provide important information about the patient's
      outcome and prognosis.

PMID- 25577254
TI  - Light adaptation of the unicellular red alga, Cyanidioschyzon merolae, probed by
      time-resolved fluorescence spectroscopy.
AB  - Photosynthetic organisms change the quantity and/or quality of their pigment
      protein complexes and the interactions among these complexes in response to light
      conditions. In the present study, we analyzed light adaptation of the unicellular
      red alga Cyanidioschyzon merolae, whose pigment composition is similar to that of
      cyanobacteria because its phycobilisomes (PBS) lack phycoerythrin. C. merolae
      were grown under different light qualities, and their responses were measured by
      steady-state absorption, steady-state fluorescence, and picosecond time-resolved
      fluorescence spectroscopies. Cells were cultivated under four monochromatic light
      emitting diodes (blue, green, yellow, and red), and changes in pigment
      composition and energy transfer were observed. Cells grown under blue and green
      light increased their relative phycocyanin levels compared with cells cultured
      under white light. Energy-transfer processes to photosystem I (PSI) were
      sensitive to yellow and red light. The contribution of direct energy transfer
      from PBS to PSI increased only under yellow light, while red light induced a
      reduction in energy transfer from photosystem II to PSI and an increase in energy
      transfer from light-harvesting chlorophyll protein complex I to PSI. Differences
      in pigment composition, growth, and energy transfer under different light
      qualities are discussed. 

PMID- 25577255
TI  - Differences in energy transfer of a cyanobacterium, Synechococcus sp. PCC 7002,
      grown in different cultivation media.
AB  - Currently, cyanobacteria are regarded as potential biofuel sources. Large-scale
      cultivation of cyanobacteria in seawater is of particular interest because
      seawater is a low-cost medium. In the present study, we examined differences in
      light-harvesting and energy transfer processes in the cyanobacterium
      Synechococcus sp. PCC 7002 grown in different cultivation media, namely modified
      A medium (the optimal growth medium for Synechococcus sp. PCC 7002) and f/2 (a
      seawater medium). The concentrations of nitrate and phosphate ions were varied in
      both media. Higher nitrate ion and/or phosphate ion concentrations yielded high
      relative content of phycobilisome. The cultivation medium influenced the energy
      transfers within phycobilisome, from phycobilisome to photosystems, within
      photosystem II, and from photosystem II to photosystem I. We suggest that the
      medium also affects charge recombination at the photosystem II reaction center
      and formation of a chlorophyll-containing complex. 

PMID- 25577256
TI  - Virulence factors contributing to invasive activities of Serratia grimesii and
      Serratia proteamaculans.
AB  - Previously, we have shown that facultative pathogens Serratia grimesii and
      Serratia proteamaculans are capable to invade eukaryotic cells provided that they
      synthesize intracellular metalloprotease grimelysin or protealysin, respectively
      (Bozhokina et al. in Cell Biol Int 35(2):111-118, 2011). Noninvasive Escherichia
      coli transformed with grimelysin or protealysin gene became invasive, indicating
      that the protease is a virulence factor. Here we elucidated involvement of other
      virulence factors in the invasion of S. grimesii and S. proteamaculans. Under
      similar experimental conditions, the amount of S. proteamaculans internalized
      within human carcinoma HeLa cells was fivefold higher than that of S. grimesii.
      In accord with this, in S. proteamaculans, high activities of pore-forming
      hemolysin ShlA and extracellular metalloprotease serralysin were detected. In S.
      grimesii, activity of toxin ShlA was not detected, and the serralysin activity of
      the bacterial growth medium was very low. We also show that iron depletion
      strongly enhanced invasive activity of S. proteamaculans, increasing activities
      of hemolysin ShlA and serralysin, but did not affect S. grimesii properties.
      These results show that the invasive activity of S. proteamaculans is maintained,
      along with protealysin, by hemolysin and serralysin. On the other hand,
      grimelysin is so far the only known invasion factor of S. grimesii. 

PMID- 25577257
TI  - Sucrose metabolism in halotolerant methanotroph Methylomicrobium alcaliphilum
      20Z.
AB  - Sucrose accumulation has been observed in some methylotrophic bacteria utilizing
      methane, methanol, or methylated amines as a carbon and energy source. In this
      work, we have investigated the biochemical pathways for sucrose metabolism in the
      model halotolerant methanotroph Methylomicrobium alcaliphilum 20Z. The genes
      encoding sucrose-phosphate synthase (Sps), sucrose-phosphate phosphatase (Spp),
      fructokinase (FruK), and amylosucrase (Ams) were co-transcribed and displayed
      similar expression levels. Functional Spp and Ams were purified after
      heterologous expression in Escherichia coli. Recombinant Spp exhibited high
      affinity for sucrose-6-phosphate and stayed active at very high levels of sucrose
      (K i  = 1.0 +/- 0.6 M). The recombinant amylosucrase obeyed the classical
      Michaelis-Menten kinetics in the reactions of sucrose hydrolysis and
      transglycosylation. As a result, the complete metabolic network for sucrose
      biosynthesis and re-utilization in the non-phototrophic organism was
      reconstructed for the first time. Comparative genomic studies revealed analogous
      gene clusters in various Proteobacteria, thus indicating that the ability to
      produce and metabolize sucrose is widespread among prokaryotes. 

PMID- 25577259
TI  - Linguine sign in musculoskeletal imaging: calf silicone implant rupture.
AB  - Imaging findings of breast silicone implant rupture are well described in the
      literature. On MRI, the linguine sign indicates intracapsular rupture, while the
      presence of silicone particles outside the fibrous capsule indicates
      extracapsular rupture. The linguine sign is described as the thin, wavy hypodense
      wall of the implant within the hyperintense silicone on T2-weighted images
      indicative of rupture of the implant within the naturally formed fibrous capsule.
      Hyperintense T2 signal outside of the fibrous capsule is indicative of an
      extracapsular rupture with silicone granuloma formation. We present a rare case
      of a patient with a silicone calf implant rupture and discuss the MRI findings
      associated with this condition. 

PMID- 25577258
TI  - Conserved aspartate and lysine residues of RcsB are required for amylovoran
      biosynthesis, virulence, and DNA binding in Erwinia amylovora.
AB  - In Erwinia amylovora, the Rcs phosphorelay system is essential for amylovoran
      production and virulence. To further understand the role of conserved aspartate
      residue (D56) in the phosphor receiver (PR) domain and lysine (K180) residue in
      the function domain of RcsB, amino acid substitutions of RcsB mutant alleles were
      generated by site-directed mutagenesis and complementation of various rcs mutants
      were performed. A D56E substitution of RcsB, which mimics the phosphorylation
      state of RcsB, complemented the rcsB mutant, resulting in increased amylovoran
      production and gene expression, reduced swarming motility, and restored
      pathogenicity. In contrast, D56N and K180A or K180Q substitutions of RcsB did not
      complement the rcsB mutant. Electrophoresis mobility shift assays showed that
      D56E, but not D56N, K180Q and K180A substitutions of RcsB bound to promoters of
      amsG and flhD, indicating that both D56 and K180 are required for DNA binding.
      Interestingly, the RcsBD56E allele could also complement rcsAB, rcsBC and rcsABCD
      mutants with restored virulence and increased amylovoran production, indicating
      that RcsB phosphorylation is essential for virulence of E. amylovora. In
      addition, mutations of T904 and A905, but not phosphorylation mimic mutation of
      D876 in the PR domain of RcsC, constitutively activate the Rcs system, suggesting
      that phosphor transfer is required for activating the Rcs system and indicating
      both A905 and T904 are required for the phosphatase activity of RcsC. Our results
      demonstrated that RcsB phosphorylation and dephosphorylation, phosphor transfer
      from RcsC are essential for the function of the Rcs system, and also suggested
      that constitutive activation of the Rcs system could reduce the fitness of E.
      amylovora.

PMID- 25577260
TI  - CORR (r) curriculum--orthopaedic education: operative assessment and the ACGME
      milestones: time for change.

PMID- 25577261
TI  - Betaine supplementation prevents fatty liver induced by a high-fat diet: effects
      on one-carbon metabolism.
AB  - The purpose of this study was to examine the effects of betaine supplementation
      on the regulation of one-carbon metabolism and liver lipid accumulation induced
      by a high-fat diet in rats. Rats were fed one of three different liquid diets:
      control diet, high-fat diet and high-fat diet supplemented with betaine. The
      control and high-fat liquid diets contained, respectively, 35 and 71 % of energy
      derived from fat. Betaine supplementation involved the addition of 1 % (g/L) to
      the diet. After three weeks on the high-fat diet the rats had increased total
      liver fat concentration, liver triglycerides, liver TBARS and plasma TNF-alpha.
      The high-fat diet decreased the hepatic S-adenosylmethionine concentration and
      the S-adenosylmethionine/S-adenosylhomocysteine ratio compared to the control as
      well as altering the expression of genes involved in one-carbon metabolism.
      Betaine supplementation substantially increased the hepatic S-adenosylmethionine
      concentration (~fourfold) and prevented fatty liver and hepatic injury induced by
      the high-fat diet. It was accompanied by the normalization of the gene expression
      of BHMT, GNMT and MGAT, which code for key enzymes of one-carbon metabolism
      related to liver fat accumulation. In conclusion, the regulation of the
      expression of MGAT by betaine supplementation provides an additional and novel
      mechanism by which betaine supplementation regulates lipid metabolism and
      prevents accumulation of fat in the liver. 

PMID- 25577262
TI  - MicroRNA deregulation in parathyroid tumours suggests an embryonic signature.
AB  - Primary hyperparathyroidism is a common endocrine disorder caused by abnormal
      tumour parathyroid cell proliferation. Parathyroid tumours show a great
      variability both in clinical features, such as the severity of PTH secretion, the
      rate and the pattern of cell proliferation, and genetic background. Studies
      aiming to develop new diagnostic markers and therapeutic approaches need a deeper
      definition of this variability. Dysregulation of microRNAs (miRNAs) has been
      shown to play an essential role in the development and progression of cancer.
      MiRNAs are small noncoding RNAs that inhibit the translation and stability of
      messenger RNAs (mRNAs). Here, data about the miRNA expression pattern in
      parathyroid normal and tumour glands were reviewed. Though available data in
      parathyroid tumours are very limited, the expression pattern of a subset of
      specific miRNAs clearly discriminated parathyroid carcinomas from normal
      parathyroid glands and, more clinically relevant, from parathyroid adenomas.
      Investigation showed that parathyroid tumours were characterized by an embryonic
      expression pattern of miRNAs such as miR-296, or the miRNA clusters C19MC and miR
      371-3, typically in stem cells committed to differentiation or during human
      embryonic development, respectively. Further, miRNA profiles were correlated with
      tumour aggressive behaviour. Moreover, the interaction with the oncosuppressor
      menin suggests that miRNAs might modulate the function of the known
      oncosuppressors or oncogenes involved in parathyroid tumourigenesis and thus
      overseeing the tumour phenotype. In conclusion, miRNAs might provide new
      diagnostic markers and new therapeutic approaches by developing molecular miRNA
      targeted therapies for the cure of parathyroid tumours, whose unique option is
      surgery. 

PMID- 25577263
TI  - Perspectives on osteoporosis therapies.
AB  - Osteoporosis is a skeletal disease which predisposes to fragility fractures with
      high morbidity and economic impact, and, therefore, the goal of any osteoporosis
      treatment is to reduce the fracture risk. In the various forms of osteoporosis an
      imbalance between bone resorption and apposition is present, that generally leads
      to a reduction of bone mineral density and bone quality, and finally to the
      increased fracture risk. Nowadays, several drugs are available with a
      demonstrated anti-fracturative effect obtained by inhibiting bone resorption or
      stimulating bone formation. However, their use is not free from limitations and
      side effects. Importantly, to date, the available antiresorptive drugs have also
      an inhibiting, though to a lesser extent, effect on bone apposition and,
      similarly, the anabolic drugs lead to an increase also of bone resorption.
      Advances in our knowledge about bone biology, with molecular insights into
      mechanisms underlying osteoblast, osteoclast, and osteocyte activity, have led to
      the recognition of new potential targets and consequently to the formulation of
      new therapeutic agents to treat osteoporosis. New potential developments among
      the antiresorptive drugs include cathepsin K inhibitors and among the
      osteoanabolic drugs those activating the Wnt signaling pathway, such as the
      monoclonal antibodies against sclerostin. The novelty of these compounds is that
      their mechanism of action gives the exciting possibility to uncouple bone
      resorption and bone formation, and data available so far appear to be promising.
      Finally, several new therapeutic targets are under investigation in preclinical
      studies which could open further approaches to treat osteoporosis in the future. 

PMID- 25577264
TI  - Metabolomic Approaches to Defining the Role(s) of GABArho Receptors in the Brain.
AB  - The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) acts through
      various types of receptors in the central nervous system. GABArho receptors,
      defined by their characteristic pharmacology and presence of rho subunits in the
      channel structure, are poorly understood and their role in the cortex is ill
      defined. Here, we used a targeted pharmacological, NMR-based functional
      metabolomic approach in Guinea pig brain cortical tissue slices to identify a
      distinct role for these receptors. We compared metabolic fingerprints generated
      by a range of ligands active at GABArho and included these in a principal
      components analysis with a library of other metabolic fingerprints obtained using
      ligands active at GABAA and GABAB, with inhibitors of GABA uptake and with
      compounds acting to inhibit enzymes active in the GABAergic system. This enabled
      us to generate a metabolic "footprint" of the GABAergic system which revealed
      classes of metabolic activity associated with GABArho which are distinct from
      other GABA receptors. Antagonised GABArho produce large metabolic effects at
      extrasynaptic sites suggesting they may be involved in tonic inhibition. 

PMID- 25577265
TI  - Gallstone-related disease in the elderly: is there room for improvement?
AB  - BACKGROUND AND AIM: Elderly patients are frequently affected by gallstone-related
      disease. Current guidelines support cholecystectomy after a first acute biliary
      complication. In the aging, these recommendations are irregularly followed.
      METHODS: We analyzed data from patients 65 or older admitted between June 30,
      2004 and June 30, 2013 with a diagnosis of acute pancreatitis, cholangitis, or
      cholecystitis. Diagnosis and severity assessment were defined according to
      current guidelines. Harms, mortality, and cholecystectomy rates were evaluated.
      Baseline factors independently predicting cholecystectomy were identified.
      RESULTS: A total of 491 patients were included. The median age was 78.8 years,
      and 51.7 % were women. Acute cholecystitis was present in 51.7 %, acute
      pancreatitis in 36.5 %, and acute cholangitis in 11.8 %. Cholecystectomy was
      performed in 47.1 %. Age, myocardial infarct, dementia, diabetes, nonmetastatic
      tumor, and severe liver disease were risk factors for not undergoing surgery.
      Complications related to hospital stay appeared in 33 % of patients. Surgery,
      cholecystostomy, and ERCP presented harms in 21-25 %. Overall mortality rate was
      5.4 %: 10.4 % in acute cholangitis, 6.8 % in acute cholecystitis, and 2.2 % in
      acute pancreatitis. Mild cases presented a 1.3 % mortality, while 28.6 % of
      severe cases died. After discharge, 24.7 % of patients presented a new biliary
      complication, 9.7 % of them severe. Relapse was more frequent in patients managed
      without invasive procedures, 42.3 % than in cholecystectomy patients, 9.9 % (p <
      0.001) and than in ERCP patients, 19.4 % (p = 0.01). CONCLUSIONS: Cholecystectomy
      should be recommended to elderly patients after a first acute biliary
      complication. If not previously performed, ERCP should be offered as an
      alternative when surgery is contraindicated or refused.

PMID- 25577266
TI  - Variants of varices: is it all "downhill" from here?

PMID- 25577267
TI  - Radiation-Free ERCP in Pregnancy: A "Sound" Approach to Leaving No Stone
      Unturned.

PMID- 25577268
TI  - Discrimination of normal and esophageal cancer plasma proteomes by MALDI-TOF mass
      spectrometry.
AB  - BACKGROUND: Most patients presenting with symptoms of esophageal cancer (EC) have
      advanced disease. Even with resection, the cure rate is extremely low due to
      local recurrence and metastatic disease. Early detection and effective
      therapeutic intervention are essential to improve survival. AIMS: This study
      tested the hypothesis that the presence of EC modulates concentrations of
      specific plasma proteins and peptides, potentially allowing discrimination
      between EC and controls based on mass spectrometric analysis of the respective
      plasma proteomes. METHODS: Blood samples from 79 esophageal cancer patients and
      40 age-matched normal subjects were processed to plasma, and protein/peptide sub
      fractions were isolated using HIC8 or WAX-derivatized superparamagnetic beads.
      Triplicate matrix-assisted laser desorption time-of-flight mass spectra were
      acquired for specific plasma fractions from each subject. RESULTS: HIC8 and WAX
      derivatized plasma eluates yielded 79 and 77 candidate features, respectively,
      and a Random Forest algorithm identified a subset of features whose peak
      intensities allowed discrimination between cancer patients and controls. Areas
      under the curve in receiver operating characteristic curves for HIC8 spectra were
      0.88 and 0.83 for WAX spectra. The combined feature set discriminated EC from
      control plasma with 79 % sensitivity and 79 % specificity, with positive and
      negative test likelihood ratios of >14 and 0.17, respectively. CONCLUSIONS: These
      data lay the foundation for the development of a clinically useful test for
      esophageal cancer based on statistical analysis of proteomic spectra of patient
      plasma samples. This approach will be validated by analysis of larger patient
      cohorts, development of cancer-specific classifiers, and assessment of racial
      origin imbalances.

PMID- 25577269
TI  - Racial Differences in the Prevalence of Celiac Disease in the US Population:
      National Health and Nutrition Examination Survey (NHANES) 2009-2012.
AB  - AIM: To provide an estimate of the prevalence of celiac disease by race/ethnic
      origin in large sample of US population. METHODS: Data from the 2009-2010 and
      2011-2012 NHANES were combined and analyzed. The NHANES is a nationally
      representative survey with oversampling of certain minorities. Sample-based
      frequencies were reported and weighted frequencies were used to estimate
      prevalence. RESULTS: A total of 14,701 participants were checked for tissue
      transglutaminase (tTG) and endomysial (EMA) IgA antibodies. Seventy-four
      participants had positive tTG and/or EMA corresponding to prevalence of 0.79 %
      (95 % CI 0.54-1.04 %). Non-Hispanic white were more likely to be positive for
      both compared with other races (72.0 vs 31.7 %; p = 0.010) and less likely to be
      weakly positive for tTG but positive for EMA (3.6 vs 26.4 %; p = 0.03). The
      prevalence of positive serology according to race was as follows: 1.08 % (95 % CI
      0.70-1.45 %) in non-Hispanic white, 0.23 % (95 % CI 0.03-0.43 %) in Mexican, 0.22
      % (95 % CI 0.01-0.44 %) in non-Hispanic black, 0.38 % (95 % CI 0.00-0.89 %) in
      "other Hispanic," and 0.15 % (95 % CI 0.00-0.34 %) in other races including
      multiracial and undeterminable in non-Hispanic Asian due to the presence of only
      one positive EMA test. 0.9 % of the NHANES sample participants followed gluten
      free diet. Of this group of participants, 85 % were never diagnosed with celiac
      disease and 99 % of them had negative celiac disease serology. CONCLUSIONS:
      Potentially 0.79 % of the general US population demonstrate serologic evidence of
      celiac disease autoimmunity. The prevalence is 4-8 times higher among non
      Hispanic white compared with other races. Close to 1 % of the population is
      electively following gluten-free diet despite having little evidence of the
      disease.

PMID- 25577270
TI  - Endoscopic treatment of patients with bile duct stricture after cholecystectomy:
      factors predicting recurrence in the long term.
AB  - BACKGROUND AND AIMS: Endoscopic treatment is effective in the treatment of
      patients with bile duct injury after cholecystectomy. We aimed to investigate the
      long-term results of endoscopic treatment, factors predicting the recurrence of
      the stricture, and to determine the optimal endoscopic treatment. METHODS: The
      study was a retrospective cohort analysis and conducted at a tertiary referral
      center in patients with major bile duct injury (Strasberg E1-4 and E5 patients
      with main bile duct injury). Patients with minor injury (Luschka and cystic duct
      leakage), complete transection, and isolated aberrant bile duct injuries were
      excluded. RESULTS: The study group included 156 patients. The median follow-up
      period after stent removal was 6.5 years (range 1-16.5). Recurrence was seen in
      18 patients (11 %) after a median duration of 9 months (range 2-96). Multivariate
      regression analysis revealed that the most important factors predicting the
      success of endoscopic treatment were: Rome type of treatment (inserting
      increasing number of stents every 3-4 months) (odds ratio 23.8, 95 % CI 1.46
      390.7, p = 0.026) instead of Amsterdam-type treatment (replacing two 10F biliary
      stents every 3-4 months) and dilation of the stricture diameter to at least 76 %
      of the common bile duct diameter at the end of stent treatment (odds ratio 25.9,
      95 % CI 2.46-272.7, p = 0.007). CONCLUSIONS: Endoscopic treatment is an effective
      method in the treatment of patients with bile duct stricture after
      cholecystectomy. Inserting multiple stents as much as possible without leaving a
      scar in the bile ducts should be aimed.

PMID- 25577271
TI  - Connecting the dots between gastrointestinal motility and symptoms using wireless
      motility capsule testing.

PMID- 25577272
TI  - Osteopontin knockout does not influence the severity of rectal damage in a
      preclinical model of radiation proctitis in mice.
AB  - BACKGROUND: Radiation damage to the normal gut is a dose-limiting factor in the
      application of radiation therapy to treat abdominal and pelvic cancers. All
      tissue cell types react in concert to orchestrate an acute inflammatory reaction
      followed by a delayed chronic scarring process. Osteopontin (OPN) is a
      matricellular protein known to be involved in various physiological but also
      pathological processes such as tissue inflammation and fibrosis. AIMS: The aim of
      our study was to determine whether OPN knockout influences the severity of
      radiation proctitis and to investigate the role of OPN in the development of
      radiation-induced gut damage. RESULTS: Here we show that human radiation
      proctitis is associated with increased immunostaining of the intracellular and
      extracellular/matrix-linked isoforms of OPN. Moreover, endothelial cells in vitro
      and rectal tissue in a preclinical model of radiation proctitis in mice both
      respond to radiation exposure by a sustained increase in OPN mRNA and protein
      levels. Genetic deficiency of OPN did not influence radiation-induced rectal
      damage and was associated with significantly decreased animal survival. The acute
      and late radiation injury scores were similar in OPN-null mice compared with
      their control littermates. CONCLUSION: This study shows that in our model and
      given the pleiotropic actions of OPN in tissue inflammation and fibrosis, further
      studies are necessary to understand the precise roles of OPN in radiation-induced
      proctitis and to determine whether OPN is a useful therapeutic tool in prevention
      of radiation-induced intestinal tissue injury.

PMID- 25577273
TI  - Prevalence of advanced colorectal neoplasm after kidney transplantation:
      surveillance based on the results of screening colonoscopy.
AB  - BACKGROUND AND AIM: The aim of this study was to determine whether the prevalence
      of advanced colorectal neoplasms increases in kidney transplant recipients and to
      define the appropriate duration for surveillance colonoscopy after kidney
      transplantation (TPL). METHODS: Our study consisted of 248 kidney transplant
      patients who underwent a colonoscopy at Seoul National University Hospital from
      1996 to 2008. For each patient, two or more age- and sex-matched controls were
      identified from a population of asymptomatic individuals. RESULTS: Twenty (8.1 %)
      patients had advanced colonic neoplasms, including colorectal cancers (four
      patients, 1.6 %), after kidney TPL. A case-control study showed that the odds of
      advanced colonic neoplasms occurring in TPL patients were 2.3 times greater than
      in the matched subjects. In addition, TPL patients 50 years of age or older had
      an approximate 5.4-fold higher risk of developing advanced neoplasms than did the
      matched subjects (OR 5.370; 95 % CI 2.543-11.336; P < 0.001). Age and history of
      advanced neoplasms were associated with an increased risk of developing advanced
      neoplasms after TPL. The 5-year cumulative incidence rate of advanced neoplasms
      was 3.6 % in the 82 patients with normal or non-advanced adenomas detected via
      screening colonoscopy before TPL. CONCLUSIONS: Colonoscopy is recommended for
      patients before and after kidney TPL, especially for those 50 years of age or
      older. Colonoscopy surveillance after TPL is warranted strictly according to the
      baseline risk stratification.

PMID- 25577274
TI  - Strong expression of HBME-1 associates with high-risk clinicopathological factors
      of papillary thyroid carcinoma.
AB  - Thyroid cancer comprises a heterogeneous group of lesions with great diversity of
      biological behaviour. Markers which could help clinicians to identify high-risk
      patients for tailored optimization of clinical management are of crucial
      importance. HBME-1 protein level was analysed immunohistochemically using
      routinely prepared archival tissue sections of a broad range of papillary thyroid
      carcinoma (PTC) variants and in corresponding lymph node metastases (LNM). The
      results were evaluated in comparison with clinicopathological features of PTC.
      Positive immunoreaction was noticed in most classical (83/92; 90.2 %), follicular
      (60/71; 84.5 %) and trabecular (4/5; 80.0 %) variants of PTC. All cases of
      macrofollicular, Warthin-like and diffuse sclerosing PTC variants were HBME-1
      positive (4/4, 3/3, 2/2; 100 % respectively). Tall cell and solid PTC variants
      showed diversity of staining (2/3; 66.67 % and 13/23; 56.52 % respectively),
      while PTCs with mixed histological pattern containing insular areas were mainly
      weakly positive (2/5; 40.0 %). A single case of clear cell PTC variant showed no
      reaction. Moreover, all matched metastatic PTC into lymph nodes (LNM) were HBME-1
      positive (17/17; 100 %) and expressed HBME-1 in a similar pattern to the matched
      primary tumour. We also found a statistically significant association between
      high HBME-1 expression and the presence of lymph node metastasis, advanced pT
      status and pTNM stage (P < 0.05), but only a tendency for association with
      extrathyroidal invasion of the tumour (P = 0.058). Therefore, we recommend using
      immunoexpression of HBME-1 as useful mean to increase the likelihood of detecting
      most PTC variants and to predict some unfavourable clinical parameters in these
      patients.

PMID- 25577275
TI  - Pathology of thyroglossal duct: an institutional experience.
AB  - Thyroglossal duct (TGD) is a developmental anomaly in which a remnant of the
      thyroid anlage is left in the neck during its descent from the foramen cecum of
      tongue to final pretracheal position. A persistent duct can lead to thyroglossal
      duct cyst (TGDC). Histologically, TGDC contains an epithelial lining of squamous
      or pseudostratified ciliated columnar epithelium and ectopic thyroid gland tissue
      in the duct wall. TGD-associated malignancy is rare, and the majority is
      papillary thyroid carcinoma (PTC). A total of 242 patients with a diagnosis of
      TGD-associated lesions were identified in our institute. Two hundred and
      seventeen cases were diagnosed as TGDC. Sixty-eight of 217 (31.3 %) cases of TGDC
      had ectopic thyroid tissue in the cystic wall. Thirty-nine cases had preoperative
      fine needle aspiration (FNA). Of these cases, 37 of 39 (94.9 %) demonstrated
      macrophages and 19 (48.7 %) also showed cells of squamous and/or columnar
      epithelial lining. Only two cases showed rare thyroid follicular cells. Thyroid
      carcinoma was identified in 18 of 242 (7.4 %) cases. All cases were diagnosed as
      PTC including 12 cases of classic PTC (66.7 %), 3 cases of follicular variant
      (16.7 %), 2 cases of tall cell variant (11.1 %), and 1 case of classic PTC with
      focal tall cell features (5.6 %). Nine cases had TGD component (either epithelial
      lining cysts or ectopic thyroid tissue). Ten patients also underwent total
      thyroidectomy (67 %). Of these patients, four had no tumor and one had an
      incidental medullary carcinoma. Five of 10 (50 %) cases had incidental PTC with a
      size range of 0.1-0.3 cm. Five patients had follow-up by imaging studies; no
      suspicious or nodular lesions were found in the thyroid. In conclusion, we report
      an institutional case cohort of 242 patients with TGD-associated lesions,
      including 217 TGDC and 18 cases of PTC. Only seven cases fulfilled the diagnostic
      criteria of TGD-associated PTC, i.e., the presence of components of TGD and a
      normal thyroid. In the remaining 11 cases, we could not differentiate with
      certainty between pyramidal primary thyroid PTC/Delphian node metastasis or TGD
      associated PTC.

PMID- 25577276
TI  - Laparoscopic ventral rectopexy using biologic mesh for the treatment of
      obstructed defaecation syndrome and/or faecal incontinence in patients with
      internal rectal prolapse: a critical appraisal of the first 100 cases.
AB  - BACKGROUND: Laparoscopic ventral mesh rectopexy (LVR) is gaining wider acceptance
      as the preferred procedure to correct internal as well as external rectal
      prolapse associated with obstructed defaecation syndrome and/or faecal
      incontinence. Very few reports exist on the use of biologic mesh for LVR. The aim
      of our study was to report the complication and recurrence rate of our first 100
      cases of LVR for symptomatic internal rectal prolapse and/or rectocele using a
      porcine dermal collagen mesh. METHODS: Prospectively collected data on LVR for
      internal rectal prolapse were analysed. Surgical complications and functional
      results in terms of faecal incontinence (measured with the Faecal Incontinence
      Severity Index = FISI) and constipation (measured with the Wexner Constipation
      Score = WCS) at 3, 6 and 12 months were analysed. It was considered an
      improvement if FISI or WCS scores were reduced by at least 25 % and a cure if the
      FISI score decreased to <10 and the WCS decreased to <5. RESULTS: Between April
      2009 and April 2013, 100 consecutive female patients (mean age 63 years, range 24
      88 years) underwent LVR. All patients had internal rectal prolapse (grade III [n
      = 25] and grade IV [n = 75] according to the Oxford classification) and
      rectocele. Mean operative time was 85 +/- 40 min. Conversion rate to open
      technique was 1 %. There was no post-operative mortality. Overall 16 patients (16
      %) experienced 18 complications, including rectal perforation (n = 1), small
      bowel obstruction (n = 2), urinary tract infection (n = 8), subcutaneous
      emphysema (n = 3), wound haematoma (n = 2), long lasting sacral pain (n = 1) and
      incisional hernia (1). Median post-operative length of stay was 2 days. Ninety
      eight out of 100 patients completed follow-up. At the end of follow-up, the mean
      FISI score improved from 8.4 (+/-4.0 standard deviation (SD) p = 0.003) to 3.3 +/
      2.3 SD (p = 0.04). Incontinence improved in 37 out of 43 patients (86 %), and 31
      patients (72 %) were cured. Similarly, the mean WCS score improved from 18.4 +/-
      11.6 SD to 5.4 +/- 4.1 SD (p = 0.04). Constipation improved in 82 out of 89
      patients (92 %), and 70 patients (79 %) were cured. No worsening of continence
      status, constipation or sexual function was observed. Fourteen patients (14 %)
      experienced persistence or recurrence of prolapse. CONCLUSIONS: LVR using
      biologic mesh is a safe and effective procedure for improving symptoms of
      obstructed defaecation and faecal incontinence in patients with internal rectal
      prolapse associated with rectocele.

PMID- 25577277
TI  - Chronic hepatitis C virus infection triggers spontaneous differential expression
      of biosignatures associated with T cell exhaustion and apoptosis signaling in
      peripheral blood mononucleocytes.
AB  - Persistent hepatitis C virus (HCV) infection appears to trigger the onset of
      immune exhaustion to potentially assist viral persistence in the host, eventually
      leading to hepatocellular carcinoma. The role of HCV on the spontaneous
      expression of markers suggestive of immune exhaustion and spontaneous apoptosis
      in immune cells of chronic HCV (CHC) disease largely remain elusive. We
      investigated the peripheral blood mononuclear cells of CHC patients to determine
      the spontaneous recruitment of cellular reactive oxygen species (cROS),
      immunoregulatory and exhaustion markers relative to healthy controls. Using a
      commercial QuantiGenePlex((r)) 2.0 assay, we determined the spontaneous
      expression profile of 80 different pro- and anti-apoptotic genes in persistent
      HCV disease. Onset of spontaneous apoptosis significantly correlated with the up
      regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase
      2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160.
      Besides, spontaneous differential surface protein expression suggestive of T cell
      inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4
      on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14,
      Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1,
      Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our
      observation suggests the spontaneous onset of apoptosis signaling and T cell
      exhaustion in chronic HCV disease. 

PMID- 25577278
TI  - How to enjoy laccases.
AB  - An analysis of the scientific literature published in the last 10 years reveals a
      constant growth of laccase applicative research in several industrial fields
      followed by the publication of a great number of patents. The Green Chemistry
      journal devoted the cover of its September 2014 issue to a laccase as greener
      alternative for chemical oxidation. This indicates that laccase "never-ending
      story" has found a new promising trend within the constant search for efficient
      (bio)catalysts able to meet the 12 green chemistry principles. A survey of
      ancient and cutting-edge uses of laccase in different industrial sectors is
      offered in this review with the aim both to underline their potential and to
      provide inspiration for new ones. Applications in textile and food fields have
      been deeply described, as well as examples concerning polymer synthesis and
      laccase-catalysed grafting. Recent applications in pharmaceutical and cosmetic
      industry have also been reviewed.

PMID- 25577279
TI  - Recent progress in oxygen-reducing laccase biocathodes for enzymatic biofuel
      cells.
AB  - This review summarizes different approaches and breakthroughs in the development
      of laccase-based biocathodes for bioelectrocatalytic oxygen reduction. The use of
      advanced electrode materials, such as nanoparticles and nanowires is underlined.
      The applications of recently developed laccase electrodes for enzymatic biofuel
      cells are reviewed with an emphasis on in vivo application of biofuel cells. 

PMID- 25577281
TI  - Serum levels of neopterin in gestational diabetes mellitus: the relationship with
      Apgar scores.
AB  - PURPOSE: This study was designed to evaluate neopterin levels and low Apgar
      scores in pregnancies with gestational diabetes mellitus (GDM) vs. normal control
      pregnancies. METHODS: We carried out a cross-sectional study by enrolling 81
      pregnant women with GDM and 38 pregnant women without GDM. RESULTS: Maternal and
      cord blood neopterin levels were higher in women with GDM. There was a
      significant positive association between fasting blood glucose levels and
      maternal serum neopterin levels. The results of 50-g oral glucose challenge tests
      revealed a correlation between maternal and cord neopterin levels. Pregnancies
      complicated by GDM exhibited lower fetal Apgar scores than those of control
      subjects. The levels of cord blood neopterin were inversely correlated with an
      fetal Apgar score of 1 min in patients with GDM. CONCLUSIONS: Patients with GDM
      had higher maternal and cord blood neopterin levels, and the cord blood neopterin
      levels are inversely associated with lower Apgar scores in women with GDM. The
      neopterin levels might be potential predictors of low fetal Apgar scores in women
      with GDM.

PMID- 25577282
TI  - Auditory brainstem implant candidacy in the United States in children 0-17 years
      old.
AB  - OBJECTIVES: The auditory brainstem implant (ABI) is an option for hearing
      rehabilitation in profoundly deaf patients ineligible for cochlear implantation.
      Over the past decade, surgeons have begun implanting ABIs in pediatric patients
      who are unable to receive cochlear implants due to congenital or acquired
      malformations of the inner ear. No study has examined the potential population
      level demand for ABIs in the United States (US). Herein, we aim to quantify the
      potential need for pediatric ABIs. METHODS: A systematic literature review was
      conducted to identify studies detailing the rates of congenital cochlear and/or
      cochlear nerve (CN) anomalies. Absolute indications for ABI include bilateral
      cochlea or CN aplasia (Group A), and relative indications for ABI include
      bilateral cochlea or CN hypoplasia (Group B). Data was subsequently correlated to
      the US Census Bureau, the National Health Interview Survey, and the Gallaudet
      Research Institute to provide an estimation of pediatric ABI candidates. RESULTS:
      Eleven studies documented rates of bilateral findings. Bilateral cochlea aplasia
      was identified in 0-8.7% of patients and bilateral CN aplasia in 0-4.8% of
      patients (Group A). Bilateral cochlea hypoplasia was identified in 0-8.7% of
      patients and bilateral CN hypoplasia in 0-5.4% of patients (Group B). Using
      population-level sensorineural hearing loss data, we roughly estimate 2.1% of
      potential implant candidates meet absolute indications for an ABI in the United
      States. CONCLUSION: Congenital cochlear and cochlear nerve anomalies are
      exceedingly rare. This study provides the first preliminary estimate of cochlea
      and CN aplasia/hypoplasia at the population level albeit with limitations based
      on available data. These data suggest the need for dedicated ABI centers to focus
      expertise and management.

PMID- 25577280
TI  - Molecular mechanisms of CD8(+) T cell trafficking and localization.
AB  - Cytotoxic CD8(+) T cells are potent mediators of host protection against disease
      due to their ability to directly kill cells infected with intracellular pathogens
      and produce inflammatory cytokines at the site of infection. To fully achieve
      this objective, naive CD8(+) T cells must be able to survey the entire body for
      the presence of foreign or "non-self" antigen that is delivered to draining lymph
      nodes following infection or tissue injury. Once activated, CD8(+) T cells
      undergo many rounds of cell division, acquire effector functions, and are no
      longer restricted to the circulation and lymphoid compartments like their naive
      counterparts, but rather are drawn to inflamed tissues to combat infection. As
      CD8(+) T cells transition from naive to effector to memory populations, this is
      accompanied by dynamic changes in the expression of adhesion molecules and
      chemokine receptors that ultimately dictate their localization in vivo. Thus, an
      understanding of the molecular mechanisms regulating CD8(+) T cell trafficking
      and localization is critical for vaccine design, control of infectious diseases,
      treatment of autoimmune disorders, and cancer immunotherapy. 

PMID- 25577283
TI  - Expression of aldehyde dehydrogenase family 1, member A3 in glycogen trophoblast
      cells of the murine placenta.
AB  - INTRODUCTION: Retinoic acid (RA) signaling is a well known regulator of
      trophoblast differentiation and placental development, and maternal decidual
      cells are recognized as the source of much of this RA. We explored possible
      trophoblast-derived sources of RA by examining the expression of RA synthesis
      enzymes in the developing mouse placenta, as well as addressed potential sites of
      RA action by examining the ontogeny of gene expression for other RA metabolizing
      and receptor genes. Furthermore, we investigated the effects of endogenous RA
      production on trophoblast differentiation. METHODS: Placental tissues were
      examined by in situ hybridization and assayed for RARE-LacZ transgene activity to
      locate sites of RAR signaling. Trophoblast stem cell cultures were differentiated
      in the presence of ALDH1 inhibitors (DEAB and citral), and expression of
      labyrinth (Syna, Ctsq) and junctional zone (Tpbpa, Prl7b1, Prl7a2) marker genes
      were analyzed by qRT-PCR. RESULTS: We show Aldh1a3 is strongly expressed in a
      subset of ectoplacental cone cells and in glycogen trophoblast cells of the
      definitive murine placenta. Most trophoblast subtypes of the placenta express RA
      receptor combinations that would enable them to respond to RA signaling.
      Furthermore, expression of junctional zone markers decrease in differentiating
      trophoblast cultures when endogenous ALDH1 enzymes are inhibited. DISCUSSION:
      Aldh1a3 is a novel marker for glycogen trophoblast cells and their precursors and
      may play a role in the differentiation of junctional zone cell types via
      production of a local source of RA.

PMID- 25577284
TI  - Lanostanoids with acetylcholinesterase inhibitory activity from the mushroom
      Haddowia longipes.
AB  - Nine lanostanoids, together with nine known ones, were isolated from the ethyl
      acetate extract of the fruiting bodies of the mushroom Haddowia longipes. Their
      structures were elucidated as 11-oxo-ganoderiol D, lanosta-8-en-7,11-dioxo-3beta
      acetyloxy-24,25,26-trihydroxy, lanosta-8-en-7-oxo-3beta-acetyloxy-11beta,24,25,26
      tetrahydroxy, lanosta-7,9(11)-dien-3beta-acetyloxy-24,25,26-trihydroxy, lanosta
      7,9(11)-dien-3beta-acetyloxy-24,26-dihydroxy-25-methoxy, 11-oxo-lucidadiol,
      11beta-hydroxy-lucidadiol, lucidone H and lanosta-7,9(11),24E-trien-3beta
      acetyloxy-26,27-dihydroxy by analysing their 1D/2D NMR and MS spectra. In
      addition, bioassays of inhibitory activity against acetylcholinesterase (AChE) of
      all compounds showed that thirteen compounds possessed inhibitory activity
      against AChE with the percentage inhibition ranging from 10.3% to 42.1% when
      tested at 100 MUM.

PMID- 25577285
TI  - Coccidioides species determination: does sequence analysis agree with restriction
      fragment length polymorphism?
AB  - Fifteen Coccidioides isolates were previously examined for genetic diversity
      using restriction fragment length polymorphism (RFLP); two fragment patterns were
      observed. Two isolates demonstrated one banding pattern (designated RFLP group
      I), while the remaining 13 isolates demonstrated a second pattern (designated
      RFLP group II). Recently, molecular studies supported the division of the genera
      Coccidioides into two species: Coccidioides posadasii and Coccidioides immitis.
      It has been assumed that the species division corresponds to the RFLP grouping.
      We tested this hypothesis by amplifying the ribosomal DNA internal transcribed
      spacer region as well as the dioxygenase, serine proteinase, and urease genes
      from 13 isolates previously examined by RFLP and then sequencing the PCR
      products. The appropriate species for each isolate was assigned using
      phylogenetically informative sites. The RFLP grouping agreed with the
      Coccidioides species assignment for all but one isolate, which may represent a
      hybrid. In addition, polymorphic sites among the four genes examined were in
      agreement for species assignment such that analysis of a single gene may be
      sufficient for species assignment. 

PMID- 25577286
TI  - Consensus statement on preventive and symptomatic care of leukodystrophy
      patients.
AB  - Leukodystrophies are inherited disorders whose primary pathophysiology consists
      of abnormal deposition or progressive disruption of brain myelin. Leukodystrophy
      patients manifest many of the same symptoms and medical complications despite the
      wide spectrum of genetic origins. Although no definitive cures exist, all of
      these conditions are treatable. This report provides the first expert consensus
      on the recognition and treatment of medical and psychosocial complications
      associated with leukodystrophies. We include a discussion of serious and
      potentially preventable medical complications and propose several preventive care
      strategies. We also outline the need for future research to prioritize clinical
      needs and subsequently develop, validate, and optimize specific care strategies. 

PMID- 25577288
TI  - The association of BMI and social distance towards obese individuals is mediated
      by sympathy and understanding.
AB  - The desire for social distance towards individuals with obesity as part of the
      stigmatization process has not been investigated. The aims of this study include:
      (a) determining the prevalence of social distance and its domains in a population
      based sample; (b) reporting levels of emotional response; and (c) investigating
      the association of BMI, emotional response and social distance. The data were
      derived from a large population based telephone survey in Germany (total n =
      3,003, this sub-sample n = 1008). Emotional response to individuals with obesity
      was assessed for the emotions discomfort, pity, insecurity, amusement, sympathy,
      help and incomprehension (5-point Likert scale). Social distance was measured on
      a 5-point Likert scale covering different areas of social interaction. This
      served as the dependent variable for a linear regression model and mediation
      models that included BMI and emotional response. Social distance was highest for
      job recommendation, introduction to a friend, someone with obesity marrying into
      the family and renting out a room. Means of emotional responses were highest for
      pity (Mean = 2.58), sympathy (Mean = 2.87) and wanting to help (M = 2.76). In
      regression analyses, incomprehension (b = 1.095, p < 0.001) and sympathy (b = 
      0.833, p < 0.001) and the respondents' own BMI (b = -0.145, p < 0.001) were
      significantly associated to the overall amount of social distance. Mediation
      models revealed a significant mediation effect of BMI through sympathy (b = 
      0.229, % of total effect through mediation = 10.3%) and through incomprehension
      (b = -0.057, % of total effect through mediation = 27.5%) on social distance.
      Social distance towards individuals with obesity is prevalent in the general
      public in Germany and it is associated with emotional responses. Altering the
      emotional responses may, therefore, be a starting point in anti-stigma
      interventions. Evoking sympathy and lowering incomprehension may result in lower
      overall social distance.

PMID- 25577289
TI  - Monetizing illness: the influence of disability assistance priming on how we
      evaluate the health symptoms of others.
AB  - For low-income families in the United States disability assistance has emerged as
      a critical income support program in the post-welfare reform era. This article
      explores how this monetization of illness-tying receipt of government assistance
      to a physical or mental condition-influences how individuals evaluate the
      severity of another individual's health symptoms. Using data collected through a
      nationally representative survey experiment of adults in the United States (n =
      1005) in May 2013, I find that respondents who are primed to consider the
      existence of disability assistance are less likely to rate the symptoms described
      in a hypothetical vignette as severe relative to the control group. I find
      evidence that this effect holds for both physical (back pain) and mental
      (depression) conditions for adults and behavioral conditions (ADHD) in children.
      Moreover, respondents in the experimental group were more likely to blame the
      individual for her health condition and this measure was found to partially
      mediate the effect of the disability assistance prime. These findings have
      important implications for researchers, policymakers and medical practitioners by
      illustrating how premising state assistance on a health condition may in turn
      shape how individuals evaluate the health symptoms of others.

PMID- 25577287
TI  - York platelet syndrome is a CRAC channelopathy due to gain-of-function mutations
      in STIM1.
AB  - Store-operated Ca(2+) entry is the major route of replenishment of intracellular
      Ca(2+) in animal cells in response to the depletion of Ca(2+) stores in the
      endoplasmic reticulum. It is primarily mediated by the Ca(2+)-selective release
      activated Ca(2+) (CRAC) channel, which consists of the pore-forming subunits
      ORAI1-3 and the Ca(2+) sensors, STIM1 and STIM2. Recessive loss-of-function
      mutations in STIM1 or ORAI1 result in immune deficiency and nonprogressive
      myopathy. Heterozygous gain-of-function mutations in STIM1 cause non-syndromic
      myopathies as well as syndromic forms of miosis and myopathy with tubular
      aggregates and Stormorken syndrome; some of these syndromic forms are associated
      with thrombocytopenia. Increased concentration of Ca(2+) as a result of store
      operated Ca(2+) entry is essential for platelet activation. The York Platelet
      syndrome (YPS) is characterized by thrombocytopenia, striking ultrastructural
      platelet abnormalities including giant electron-opaque organelles and massive,
      multilayered target bodies and deficiency of platelet Ca(2+) storage in delta
      granules. We present clinical and molecular findings in 7 YPS patients from 4
      families, demonstrating that YPS patients have a chronic myopathy associated with
      rimmed vacuoles and heterozygous gain-of-function STIM1 mutations. These findings
      expand the phenotypic spectrum of STIM1-related human disorders and define the
      molecular basis of YPS. 

PMID- 25577290
TI  - Multivisceral resection for advanced rectal cancer: outcomes and experience at a
      single institution.
AB  - BACKGROUND: Multivisceral resection is often required in the treatment of locally
      advanced rectal cancers. Such resections are relatively rare and oncologic
      outcomes, especially when sphincter preservation is performed, are not fully
      demonstrated. METHODS: A retrospective review was conducted of patients who
      underwent multivisceral resection for locally advanced rectal cancer with and
      without sphincter preservation. RESULTS: Sixty-one patients underwent
      multivisceral resection for rectal cancer from 2005 to 2013 with a median follow
      up of 27.8 months. Five-year overall and disease-free survival were 49.2% and
      45.3%, respectively. Thirty-four patients (55.7%) had sphincter-sparing
      operations with primary coloanal anastomosis and temporary stoma. There was no
      significant difference in overall or disease-free survival, or recurrence with
      sphincter preservation compared with those with permanent stoma. CONCLUSIONS:
      Multivisceral resection for locally advanced rectal cancer has acceptable
      oncologic and clinical outcomes. Sphincter preservation and subsequent
      reestablishment of gastrointestinal continuity does not impact oncologic outcomes
      and should be considered in many patients.

PMID- 25577291
TI  - Post-hypoxic and ischemic neuroprotection of BMP-7 in the cerebral cortex and
      caudate-putamen tissue of rat.
AB  - Previous reports have indicated that exogenous bone morphogenetic protein-7 (BMP
      7) has a neuroprotective effect after cerebral ischemia injury and promotes motor
      function recovery, but the appropriate BMP-7 concentration and time course are
      unclear. Here, we assessed endogenous BMP-7 expression in hypoxia and ischemia
      damaged brain tissues and investigated the effects of different BMP-7
      concentrations in pre- and post-hypoxic primary rat neurons. The results showed
      that BMP-7 expression was significantly higher in the ischemic hemisphere. The
      expressions of BMP-7 and caspase-3 were localized in the cytoplasm of the primary
      cerebral cortical and caudate-putamen neurons 24h after hypoxia/reoxygenation.
      After BMP-7 treatment, the number of caspase-3 positive neurons began to decrease
      with increasing BMP-7 concentrations up to 80ng/ml, but not beyond. Although the
      numbers of caspase-3-positive neurons between pre- and post-hypoxia/reoxygenation
      were not significantly different, more dendrites were observed in the groups
      treated prior to hypoxia/reoxygenation. These results suggest that increased BMP
      7 expression can be induced in the cerebral cortex and caudate-putamen both in
      vivo and in vitro in hypoxic-ischemic states. The neuroprotective mechanism of
      BMP-7 may include apoptosis suppression, and its effect was enhanced from 40 to
      80ng/ml. Pre-hypoxic BMP-7 treatment may be useful to stimulate dendrite
      sprouting in non-injured neurons. 

PMID- 25577292
TI  - Assessing intake of spices by pattern of spice use, frequency of consumption and
      portion size of spices consumed from routinely prepared dishes in southern India.
AB  - BACKGROUND: Measurement of dietary intake of spices is gaining significance
      because of recognition of their health promoting benefits as well as its use for
      risk assessment of contaminant exposures. Estimating intake of spices at the
      individual level, presents several challenges since various spices are used as an
      integrated part of a prepared food and consumed in amounts much smaller than
      other dietary components. The objective of the present study is to assess intake
      of spices at the household and individual level on the basis of pattern of spice
      use and portion size of spice consumed from routinely prepared dishes in
      Hyderabad city in Southern India. METHODS: The study was conducted in 100
      households in urban areas of Hyderabad city in India with the help of a spice
      intake questionnaire that was prepared to collect information on the pattern of
      spice use, frequency, and quantity of spice consumption of 17 spices routinely
      used in Indian cuisine. The quantity of spice intake was assessed by measuring
      portion size of spice consumed from the quantity of i) spices added in routinely
      prepared dishes and ii) the prepared dish consumed by an individual. RESULTS:
      Based on the type of dish prepared and frequency of preparing the dishes, 11 out
      of 17 spices were found to be consumed by more than 50% of the households.
      Maximum number of spices was consumed at weekly frequencies. Red chillies and
      turmeric were the most frequently consumed spices by 100% of the households. The
      mean total intake of spices was observed to be higher through dishes consumed
      daily (10.4 g/portion) than from those consumed at weekly or monthly frequencies.
      Highest portion size intake was observed for chillies (mean 3.0 g; range 0.05
      20.2 g) and lowest for nutmeg (mean 0.14 g; range 0.02-0.64 g) and mace (mean
      0.21 g; range: 0.02-0.6 g). CONCLUSIONS: The study suggested that assessment of
      intake of spices varies with frequency of use of spices and type of dish
      consumed. Portion size estimations of spices consumed and the frequency of
      consumption of the spice containing dishes facilitates in quantifying spice
      intake at the individual level.

PMID- 25577293
TI  - Role of CaMKII in cardiac arrhythmias.
AB  - Protein phosphorylation is a central mechanism in vertebrates for the regulation
      of signaling. With regard to the cardiovascular system, phosphorylation of
      myocyte targets is critical for the regulation of excitation contraction
      coupling, metabolism, intracellular calcium regulation, mitochondrial activity,
      transcriptional regulation, and cytoskeletal dynamics. In fact, pathways that
      tune protein kinase signaling have been a mainstay for cardiovascular therapies
      for the past 60 years. The calcium/calmodulin-dependent protein kinase II
      (CaMKII) is a multifunctional serine/threonine kinase with numerous roles in
      human physiology. Dysfunction in CaMKII-based signaling has been linked with a
      host of cardiovascular phenotypes including heart failure and arrhythmia, and
      CaMKII levels are elevated in human and animal disease models of heart disease.
      While nearly a decade has been invested in targeting CaMKII for the treatment of
      heart failure and arrhythmia phenotypes, to date, approaches to target the
      molecule for antiarrhythmic benefit have been unsuccessful for reasons that are
      still not entirely clear, although (1) lack of compound specificity and (2) the
      multitude of downstream targets are likely contributing factors. This review will
      provide an update on current pathways regulated by CaMKII with the goal of
      illustrating potential upstream regulatory mechanisms and downstream targets that
      may be modulated for the prevention of cardiac electrical defects. While the
      review will cover multiple aspects of CaMKII dysfunction in cardiovascular
      disease, we have given special attention to the potential of CaMKII-associated
      late Na(+) current as a novel therapeutic target for cardiac arrhythmia. 

PMID- 25577294
TI  - Association between VDR polymorphisms and rheumatoid arthritis disease:
      Systematic review and updated meta-analysis of case-control studies.
AB  - BACKGROUND: Vitamin D receptor (VDR) polymorphisms have been inconsistently
      investigated in rheumatoid arthritis (RA). However, published studies
      demonstrated differences concerning design and effect size. A meta-analysis is
      necessary to determine the magnitude of the association between VDR polymorphisms
      and RA risk. OBJECTIVE: The aim of the current study was to quantify the
      magnitude of the association between TaqI, BsmI, and FokI VDR polymorphisms with
      RA risk. METHODS: Following the Preferred Reporting Items for Systematic Reviews
      and Meta-Analyses (PRISMA) guidelines, a systematic search and meta-analysis of
      the literature were conducted. Analyses were performed in the random effects
      model by using recessive, dominant, codominant, homozygous, and allele contrast
      models. RESULTS: A total of 1703 cases and 2635 controls in 12 case-control
      studies were included in the meta-analyses. Results indicated a significant
      association between TaqI polymorphism and RA disease in homozygous, codominant
      and allele contrast models (P=0.008, P=0.015, P=0.006 and P=0.002, respectively).
      Association between BsmI polymorphism and RA risk was marginal in the dominant,
      codominant and allele contrast models (P=0.057, P=0.071, and P=0.069,
      respectively). Te association between FokI polymorphism and RA risk was
      significant in the recessive, dominant and allele contrast models (P=0.045,
      P=0.027, and P=0.013, respectively). Subgroup analysis showed that publication
      year, ethnicity, age, latitude, and estimated 25(OH)D levels influenced
      significantly the association between VDR polymorphisms and RA risk. CONCLUSION:
      TaqI and FokI VDR polymorphisms contributed significantly to RA risk. Study
      characteristics influenced the association between VDR polymorphisms and RA
      disease.

PMID- 25577295
TI  - Inhibition of ecto-ATPase activities impairs HIV-1 infection of macrophages.
AB  - Nucleotides and nucleosides are secreted into extracellular media at different
      concentrations as a consequence of different physiologic and pathological
      conditions. Ecto-nucleotidases, enzymes present on the surface of most cells,
      hydrolyze these extracellular nucleotides and reduce the concentration of them,
      thus affecting the activation of different nucleotide and nucleoside receptors.
      Also, ecto-nucleotidases are present in a number of microorganisms and play
      important roles in host-pathogen interactions. Here, we characterized the ecto
      ATPase activities present on the surface of HIV-1 particle and human macrophages
      as well. We found that the kinetic properties of HIV-1 and macrophage ecto
      ATPases are similar, suggesting that the enzyme is the same. This ecto-ATPase
      activity was increased in macrophages infected in vitro with HIV-1. Using three
      different non-related ecto-ATPase inhibitors-POM-1, ARL67156 and BG0-we showed
      that the inhibition of these macrophage and viral ecto-ATPase activities impairs
      HIV-1 infection. In addition, we also found that elevated extracellular
      concentrations of ATP inhibit HIV-1 production by infected macrophages. 

PMID- 25577296
TI  - The effectiveness of a patient at risk team comprised of predominantly ward
      experienced nurses: A before and after study.
AB  - INTRODUCTION: Improving care to deteriorating ward patients require systems to
      trigger a response and a response team. This paper describes the effectiveness of
      a Patient at Risk team (PART) comprised predominantly of experienced ward nurses.
      METHOD: The study used a single site before and after historical control design.
      The number of medical emergency team (MET) calls, cardiac arrest calls and
      hospital admissions occurring prior to the establishment of the PART (January
      December 2008 inclusive) were compared to those occurring after the team was
      established (January 2011-December 2012 inclusive). Primary outcome was the
      number of MET and cardiac arrest calls per 1000 hospital admissions. RESULTS: The
      introduction of the PART resulted in a significant reduction in ward cardiac
      arrests per 1000 admissions (MD = 0.9, 95% CI: 0.3-1.5, p = 0.009), hospital
      length of stay per 1000 admissions (MD = 294.4, 95% CI: 260.9-328.7, p <= 0.001)
      and direct ward admissions to ICU (95% CI: 0.7-5.2) but no change in the number
      of MET calls per 1000 admissions (MD = 1.3, 95% CI: -2.3-4.9, p = 0.46).
      CONCLUSION: A PART comprising of experienced ward nurses was associated with
      reduced ward cardiac arrests but no change in the number of MET calls. This
      suggests this team composition may be effective in providing care to the
      deteriorating patient.

PMID- 25577297
TI  - New photosensitizers containing the dipyridoquinoxaline moiety and their use in
      dye-sensitized solar cells.
AB  - New Ru(II) polypyridyl complexes containing two N, N bidentate ligands,
      [Ru(phendione)2dpq(COOH)2](BF4)2 (L101), {Ru(phendione)[dpq(COOH)2]2}(BF4)2
      (L102) and [Ru(phendione)dpq(COOH)2 (SCN)2](L103), (phendione=5,6 dione-1,10
      phenanthroline and dpq(COOH)2=6,7-dicarboxylicdipyrido[2,2-d:2',3'f]quinoxaline)
      have been synthesized and characterized, and attached to a TiO2 substrate to be
      tested as solar cell sensitizers. We found that the solar to electricity
      conversion efficiency of cell is strongly affected by the type of ancillary
      ligand, the efficiency of L102 (with one phendione moiety) adsorbed on TiO2
      nanocrystalline films being 2.5 times as large as that of L101 (with two
      phendione moieties) adsorbed on the same films. The effect of ancillary ligand on
      the photovoltaic performance of the complexes was compared to results of
      computational methods by ab initio DFT molecular dynamics simulations and quantum
      dynamics calculations of electronic relaxation to investigate the interfacial
      electron transfer in L101-103/TiO2-anatase nanostructures. It is found that the
      primary process in the interfacial electron-transfer dynamics involves an
      ultrafast (tau1=6 fs) electron-injection. The concepts of attribute ancillary
      ligand substitution and HOMO-LUMO alignment of dye with conduction band of
      semiconductor and electrolyte redox state are shown very helpful for tuning the
      photovoltaic properties and the rational architecture of polypyridyl
      photosensitizer with anticipated good properties.

PMID- 25577298
TI  - Aligning policy to promote cascade genetic screening for prevention and early
      diagnosis of heritable diseases.
AB  - Cascade genetic screening is a methodology for identifying and testing close
      blood relatives of individuals at increased risk for heritable conditions and
      follows a sequential process, minimizing testing costs and the number of family
      members who need to be tested. It offers considerable potential for cost savings
      and increased awareness of heritable conditions within families. CDC-classified
      Tier 1 genomic applications for hereditary breast and ovarian cancer syndrome
      (HBOC), Lynch Syndrome (LS), and familial hypercholesterolemia (FH) are
      recommended for clinical use and support the use of cascade genetic screening.
      Most individuals are unaware of their increased risk for heritable conditions
      such as HBOC, LS, and FH. Consistent implementation of cascade genetic screening
      could significantly increase awareness and prevention of heritable conditions.
      Limitations to effective implementation of cascade genetic screening include:
      insufficient genetic risk assessment and knowledge by a majority of healthcare
      providers without genetics credentials; a shortage of genetic specialists,
      especially in rural areas; a low rate of reimbursement for comprehensive genetic
      counseling services; and an individual focus on prevention by clinical guidelines
      and insurance coverage. The family-centric approach of cascade genetic screening
      improves prevention and early diagnosis of heritable diseases on a population
      health level. Cascade genetic screening could be better supported and augmented
      through changes in health policy. 

PMID- 25577299
TI  - Radiofrequency ablation plus drug-eluting beads transcatheter arterial
      chemoembolization for the treatment of single large hepatocellular carcinoma.
AB  - BACKGROUND: Our aim was to evaluate the effectiveness of the single-step combined
      therapy with radiofrequency ablation and drug-eluting beads transarterial
      chemoembolization in single hepatocellular carcinoma (HCC) larger than 3cm.
      Secondary aim was to compare the results with those obtained in a matched
      population treated with drug-eluting beads transarterial chemoembolization alone.
      METHODS: 40 consecutive cirrhotic patients with single HCC were prospectively
      enrolled and treated. Twenty-three patients had tumours between 3 and 5cm (Group
      A), and 17 larger than 5cm (Group B). Twenty cirrhotic patients with single HCC
      treated only with chemoembolization formed the control group. RESULTS: Complete
      response at 1 month was achieved in 32/40 tumours (80%). During follow-up,
      complete response was maintained in 25 patients (25/40, 62.5%), and this rate was
      higher in Group A (69.6% vs 53%, p=0.008). The group treated with combined
      therapy showed a significantly lower 2-year recurrence (48.1% vs 78.2%, p<0.001)
      and significantly higher survival (91.1% vs 60.6%, p=0.004) than the group
      treated with chemoembolization alone. CONCLUSIONS: Balloon-occluded
      radiofrequency ablation plus drug-eluting beads transarterial chemoembolization
      is an effective treatment of HCC larger than 3cm not amenable to surgical
      resection, providing better results than transarterial chemoembolization alone.
      The best results are achieved in tumours up to 5cm.

PMID- 25577300
TI  - Resveratrol improves insulin resistance, glucose and lipid metabolism in patients
      with non-alcoholic fatty liver disease: a randomized controlled trial.
AB  - BACKGROUND: Non-alcoholic fatty liver disease is a major health problem
      worldwide. Resveratrol is a natural polyphenol found in edible plants that has a
      variety of biochemical and physiological effects. AIMS: To evaluate the effect of
      resveratrol on insulin resistance, glucose and lipid metabolism in non-alcoholic
      fatty liver disease. METHODS: Double-blind, randomized, placebo-controlled trial:
      60 subjects with non-alcoholic fatty liver disease were given 2 placebo capsules
      (placebo group) or 2 150mg resveratrol capsules (resveratrol group) twice daily
      for three months. Liver ultrasound imaging, anthropometric profile, serum liver
      enzymes, insulin, glucose, C-peptide, lipid profile, and inflammation-related
      cytokines were compared pre and post-treatment. RESULTS: Compared with the
      placebo group, resveratrol significantly decreased aspartate aminotransferase,
      glucose and low-density lipoprotein cholesterol [-6.00 (-9.00, -3.00) IU/L, 
      0.64+/-0.31mmol/L, and -0.41+/-0.35mmol/L, respectively, P<=0.001] alanine
      aminotransferase, total cholesterol [-7.00 (-11.0, -2.50) IU/L and -0.67+/
      0.50mmol/L, respectively, P=0.002], and homeostasis model assessment insulin
      resistance index (-0.60+/-1.15, P=0.016). In the resveratrol group significant
      reductions of the levels of tumour necrosis factor-alpha, cytokeratin 18
      fragment, and fibroblast growth factor 21 [-0.53+/-1.30pg/mL, -26.9 (-70.3, 5.12)
      IU/L and -23.3 (-43.0, 0.31) pg/mL, respectively, P<0.05] and elevation of
      adiponectin level [1.22 (-0.37, 1.60) ng/mL, P=0.025] were observed. CONCLUSION:
      Resveratrol supplementation may benefit patients with non-alcoholic fatty liver
      disease.

PMID- 25577301
TI  - "Epsilon waves" in peripheral and precordial leads in arrhythmogenic right
      ventricular cardiomyopathy with severe right ventricular involvement.

PMID- 25577302
TI  - Early jejunostomy creation in cases of isolated hypoganglionosis: verification of
      our own experience based on a national survey.
AB  - PURPOSE: Isolated hypoganglionosis (IH) is a rare disease, with few well
      established therapeutic strategies. This study aims to verify our preliminary
      therapeutic strategies developed to date in a comparison with data obtained from
      a nationwide survey of congenital-type IH. METHODS: Of the 90 registered IH cases
      assessed in a survey of Japanese pediatric surgical departments, 40 patients who
      had initially undergone jejunostomy (JE) and 41 treated with ileostomy (IL) were
      analyzed. Thirteen patients with JE sites located less than 50 cm from the
      ligament of Treitz were defined as having undergone upper jejunostomy (UJE).
      Postsurgical plain abdominal X-ray findings and survival rates, estimated using
      the Kaplan-Meier method, were used to evaluate improvements following stoma
      creation. RESULTS: Improvements in bowel obstruction were observed in
      significantly more UJE patients (9/13) than non-UJE patients [20/63 (22 JE and 41
      IL cases); p = 0.01]. Furthermore, the JE patients demonstrated a significantly
      higher survival rate than the IL patients (p = 0.01). Following the completion of
      the 10-year follow-up period, three JE patients died after undergoing massive
      bowel resection. CONCLUSIONS: To manage IH successfully, patients should undergo
      JE less than 50 cm from the ligament of Treitz during the neonatal period.
      Properly managing the distal intestines is important for achieving long-term
      survival.

PMID- 25577303
TI  - Depression Attributes Among White Non-Hispanic and Mexican-Origin Older Men.
AB  - OBJECTIVE: Depression is associated with poor quality of life, higher healthcare
      costs, and suicide. Older, especially minority, men suffer high rates of
      depression under-treatment. Illness attributes may influence depression under
      treatment by shaping help-seeking and physician recognition in older and minority
      men. Improved understanding of depression attributes may help to close gaps in
      care for older men. The study aims are to describe the range and most frequent
      attributes of depression in a diverse sample of older men and to describe ethnic
      similarities and differences in depression attributes between white non-Hispanic
      and Mexican-origin older men. METHODS: In this qualitative study of white non
      Hispanic and Mexican-origin older men who were recruited from outpatient primary
      care clinics in central California, 77 (47 white non-Hispanic and 30 Mexican
      origin) men aged 60 and older who were identified as depressed and/or receiving
      depression treatment in the past year completed in-depth interviews covering
      their experiences of depression. Transcribed interviews were analyzed per
      established descriptive qualitative techniques. RESULTS: Twenty-one depression
      attributes were identified and 9 were present in at least 17% of the interviews.
      Men often attributed their depression to stressors such as grief/loss and spousal
      conflicts, feelings of moral failure, and poor health. Although there were
      similarities in depression attributes between the groups, we found several
      differences in the frequency of certain attributes. CONCLUSION: Similarities and
      differences in depression attributes between Mexican-origin and white non
      Hispanic older men suggest the confluence of various sociocultural factors.
      Awareness of the variety of ways that older men understand depression can help
      clinicians identify and engage them in depression treatment.

PMID- 25577304
TI  - Personality Moderates the Improvement of Depressive Symptoms After Retirement:
      Evidence from the GAZEL Cohort.
AB  - OBJECTIVE: Previous studies have suggested a positive effect of retirement on
      depressive symptoms. The present study took advantage of the large-scale,
      prospective Gaz et Electricite (GAZEL) cohort to examine whether personality
      could influence this effect. METHODS: Depressive symptoms were assessed in 1993,
      1996, 1999, 2002, 2005, and 2008 with the Center for Epidemiologic Studies
      Depression Scale (CES-D). Among the participants for which changes in depressive
      symptoms after retirement could be computed, 9,755 had completed the Buss and
      Durkee Hostility Inventory and the Bortner Type A Rating Scale in 1993.
      Covariates included age, gender, occupational grade, history of sickness absences
      for depression, and alcohol consumption. The effect of hostility and type A
      personality on changes in depressive symptoms after retirement were assessed with
      general linear models. RESULTS: Adjusting for all covariates, higher scores of
      total (p <0.001; eta(2) = 0.017), cognitive (p <0.001; eta(2) = 0.021), and
      behavioral hostility (p <0.001; eta(2) = 0.004) as well as type A personality (p
      <0.001; eta(2) = 0.002) were each associated with a smaller improvement of
      depressive symptoms after retirement. Regarding hostility subscales, only the
      association with cognitive hostility remained significant (p <0.001; eta(2) =
      0.018) when both were simultaneously entered in the model. Among participants
      meeting the CES-D threshold of clinical depression before retirement, those in
      the lowest quartile of cognitive hostility were two times more likely than those
      in the highest to fall short of this threshold after retirement (odds ratio:
      1.99; 95% confidence interval: 1.54-2.58). CONCLUSION: Individuals with high
      levels of cognitive hostility display less improvement of depressive symptoms
      after retirement.

PMID- 25577305
TI  - Australian perioperative nurses' experiences of assisting in multi-organ
      procurement surgery: a grounded theory study.
AB  - INTRODUCTION/BACKGROUND: Multi-organ procurement surgical procedures through the
      generosity of deceased organ donors, have made an enormous impact on extending
      the lives of recipients. There is a dearth of in-depth knowledge relating to the
      experiences of perioperative nurses working closely with organ donors undergoing
      multi-organ procurement surgical procedures. AIM: The aim of this study was to
      address this gap by describing the perioperative nurses experiences of
      participating in multi-organ procurement surgical procedures and interpreting
      these findings as a substantive theory. DESIGN: This qualitative study used
      grounded theory methodology to generate a substantive theory of the experiences
      of perioperative nurses participating in multi-organ procurement surgery.
      SETTING: Recruitment of participants took place after the study was advertised
      via a professional newsletter and journal. The study was conducted with
      participants from metropolitan, rural and regional areas of two Australian
      states; New South Wales and Western Australia. PARTICIPANTS: Thirty five
      perioperative nurse participants with three to 39 years of professional nursing
      experience informed the study. METHODS: Semi structured in-depth interviews were
      undertaken from July 2009 to April 2010 with a mean interview time of 60 min.
      Interview data was transcribed verbatim and analysed using the constant
      comparative method. RESULTS: The study results draw attention to the complexities
      that exist for perioperative nurses when participating in multi-organ procurement
      surgical procedures reporting a basic social psychological problem articulated as
      hiding behind a mask and how they resolved this problem by the basic social
      psychological process of finding meaning. CONCLUSION: This study provides a
      greater understanding of how these surgical procedures impact on perioperative
      nurses by providing a substantive theory of this experience. The findings have
      the potential to guide further research into this challenging area of nursing
      practice with implications for clinical initiatives, management practices and
      education.

PMID- 25577306
TI  - Skill mix, roles and remuneration in the primary care workforce: who are the
      healthcare professionals in the primary care teams across the world?
AB  - World-wide, shortages of primary care physicians and an increased demand for
      services have provided the impetus for delivering team-based primary care. The
      diversity of the primary care workforce is increasing to include a wider range of
      health professionals such as nurse practitioners, registered nurses and other
      clinical staff members. Although this development is observed internationally,
      skill mix in the primary care team and the speed of progress to deliver team
      based care differs across countries. This work aims to provide an overview of
      education, tasks and remuneration of nurses and other primary care team members
      in six OECD countries. Based on a framework of team organization across the care
      continuum, six national experts compare skill-mix, education and training, tasks
      and remuneration of health professionals within primary care teams in the United
      States, Canada, Australia, England, Germany and the Netherlands. Nurses are the
      main non-physician health professional working along with doctors in most
      countries although types and roles in primary care vary considerably between
      countries. However, the number of allied health professionals and support
      workers, such as medical assistants, working in primary care is increasing.
      Shifting from 'task delegation' to 'team care' is a global trend but limited by
      traditional role concepts, legal frameworks and reimbursement schemes. In
      general, remuneration follows the complexity of medical tasks taken over by each
      profession. Clear definitions of each team-member's role may facilitate optimally
      shared responsibility for patient care within primary care teams. Skill mix
      changes in primary care may help to maintain access to primary care and quality
      of care delivery. Learning from experiences in other countries may inspire policy
      makers and researchers to work on efficient and effective teams care models
      worldwide. 

PMID- 25577307
TI  - Experiencing patient death in clinical practice: nurses' recollections of their
      earliest memorable patient death.
AB  - BACKGROUND: Death and dying are inevitable life encounters, but a nurse's first
      experience with patient death may pose considerable cognitive, emotional and
      clinical challenges. This paper reports the findings of the second phase of a
      study; the first has been reported elsewhere. This phase explored the earliest
      memorable patient death experiences of New Zealand registered nurses. METHOD: A
      purposeful, self-selected sub-sample of a larger study of New Zealand registered
      nurses, took part in individual face-to-face semi-structured interviews.
      Interpretative phenomenological analysis was utilised to seek to understand
      participants' experiences. Thematic analysis was undertaken to identify emerging
      themes, with participants' own words used as theme headings, where their phrases
      provided succinct or powerful descriptors. RESULTS: A diverse participant group
      of twenty, currently practising, New Zealand registered nurses provided rich and
      detailed descriptions of their earliest memorable experience with patient death.
      Participants from a variety of training backgrounds described patient deaths,
      which occurred in a range of settings - some only a few months prior, others -
      more than thirty years ago. Seven emergent themes, and features of more positive,
      or negative experiences were identified: Event Significance; Emotional
      Challenges; Sharing the Experience; Learning; Feeling Unprepared, Responses to
      Death and Finding Benefits. CONCLUSION: For participants in this study, there was
      considerable evidence that their earliest memorable patient death was a
      significant event. Furthermore, although most participants' experiences were
      characterised by emphatic or poignant description, there was most often a balance
      of challenges and rewards.

PMID- 25577308
TI  - Does early-life income inequality predict self-reported health in later life?
      Evidence from the United States.
AB  - We investigate the association between adult health and the income inequality
      they experienced as children up to 80 years earlier. Our inequality data track
      shares of national income held by top percentiles from 1913 to 2009. We average
      those data over the same early-life years and merge them to individual data from
      the Panel Study of Income Dynamics data for 1984-2009. Controlling for
      demographic and economic factors, we find both men and women are statistically
      more likely to report poorer health if income was more unequally distributed
      during the first years of their lives. The association is robust to alternative
      specifications of income inequality and time trends and remains significant even
      when we control for differences in overall childhood health. Our results
      constitute prima facie evidence that adults' health may be adversely affected by
      the income inequality they experienced as children. 

PMID- 25577309
TI  - Epithelial-mesenchymal transition: a key mechanism for cigarette smoke-associated
      pulmonary fibrosis in COPD?

PMID- 25577310
TI  - "Cor bovinum": An ambiguous chest radiography.

PMID- 25577311
TI  - Social motility in African trypanosomes: fact or model?
AB  - African trypanosomes grown on agarose plates exhibit behaviours akin to social
      motility. This phenomenon has not been observed in vivo so far but recently
      turned out to be instrumental in the definition of two specific stages of the
      parasite cycle and as a tool to probe for trypanosome sensing functions. 

PMID- 25577312
TI  - Comparison of 3 video laryngoscopes against the Miller laryngoscope for tracheal
      intubation during infant resuscitation.

PMID- 25577313
TI  - Air pollution and activation of mobile medical team for out-of-hospital cardiac
      arrest.
AB  - BACKGROUND: The association between air pollution exposure and cardiovascular
      events is well established, and the effect of short-term exposure on out-of
      hospital cardiac arrest (OHCA) has received some attention. The effect of air
      pollution exposure and the activation of mobile intensive care units (MICUs) for
      cardiac arrest have never been studied. OBJECTIVE: We analyzed associations
      between air pollutants and MICU activation for OHCA. METHOD: This is a
      retrospective study including 4558 patients with OHCA and MICU activation from
      2007 to 2012. A time-stratified case crossover design was used. Particulate
      matter (PM) of median aerodynamic diameter less than 2.5 MUm (PM2.5), less than
      10 MUm, and ozone were the 3 main pollutants used to determine the effects of
      pollution exposure on the event. RESULTS: A daily average increase of 27.6
      MUg/m(3) in ozone was associated with an increase of MICU activation for OHCA the
      following day (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.03-1.22).
      For women, a daily average increase of 27.6 MUg/m(3) in ozone was associated with
      an increase of MICU activation for OHCA the following day (OR, 1.19; 95% CI, 1.01
      1.37). An hourly average increase of 10.5 MUg/m(3) in PM2.5 was associated with
      an increase of MICU activation for OHCA in the current hour (OR, 1.11; 95% CI,
      1.02-1.19). For men, an increase in PM2.5 was associated with an increase in MICU
      activation for OHCA the current hour (OR, 1.10; 95% CI, 1.01-1.20). No
      association was found with PM of median aerodynamic diameter less than 10 MUm.
      CONCLUSION: An association was found between air pollution and MICU activation
      for OHCA (ozone and PM2.5).

PMID- 25577314
TI  - Collagen Q--a potential target for autoantibodies in myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies
      targeting proteins expressed at the neuromuscular junction (NMJ). In most cases
      the targets are acetylcholine receptor (AChR), muscle-specific tyrosine kinase
      (MuSK), or occasionally low-density lipoprotein receptor-related protein 4
      (LRP4), but there is still a group of patients, often called seronegative MG
      (SNMG), with unknown antibody targets. One potential target is collagen Q (COLQ),
      which is restricted to the NMJ and is crucial for anchoring the NMJ-specific form
      of acetylcholinesterase (AChE). 415 serum samples with a clinical diagnosis of MG
      and 43 control samples were screened for the presence of COLQ autoantibodies
      using a cell-based assay (CBA) with HEK293 cells overexpressing COLQ at the cell
      surface. COLQ antibodies were detected in 12/415 MG sera and in one/43 control
      samples. Five of the COLQ-Ab+individuals were also positive for AChR-Abs and 2
      for MuSK-Abs. Although the COLQ antibodies were only present at low frequency,
      and did not differ significantly from the small control cohort, further studies
      could address whether they modify the clinical presentation or the benefits of
      anti-cholinesterase therapy. 

PMID- 25577315
TI  - Neurological outcome and predictive factors of idiopathic optic neuritis in
      China.
AB  - BACKGROUND: The neurological outcome and predictive factors of idiopathic optic
      neuritis (ION) in China are largely unknown. OBJECTIVE: The aim of this paper is
      to study the neurological outcome of Chinese ION and to investigate the early
      predictors for multiple sclerosis (MS) and neuromyelitis optica spectrum
      disorders (NMOSD). METHOD: Retrospective medical record review and supplementary
      follow-up of 107 ION patients was performed. Statistical analysis of the baseline
      characteristics as risk factors for ION patients converting into MS or NMOSD was
      performed. RESULTS: With an average disease course of 9.5years, 19 of the 107
      (17.7%) ION patients developed either MS (9, 8.4%) or NMOSD (10, 9.3%). The
      estimated 5-year and 10-year combined accumulative risk rates were 14.1% and
      26.0%, respectively. Significantly higher estimated accumulative conversion risk
      was found in female versus male (P=0.047), adult versus children (P=0.032),
      patients with brain MRI lesions versus patients without leasions (P=0.026),
      patients with CSF positive oligoclonal bands and/or elevated IgG index versus
      without (P=0.003) and patients with poor visual recovery versus patients with
      good recovery (P=0.007). Furthermore, brain white matter lesions and good visual
      recovery were statistically more common typically in MS converters compared with
      the NMOSD converters (P=0.01 and P=0.006, respectively). CONCLUSION: The combined
      conversion rate for ION to MS/NMO in Chinese population was lower than the
      reported rate for Western countries. In addition to some previously reported high
      risk factors, white matter lesions on the brain MRI at baseline and good visual
      recovery were found to be good predictors for Chinese ION converting into MS
      whereas poor visual recovery with a normal brain MRI suggested a higher
      likelihood of the ION converting into NMOSD.

PMID- 25577316
TI  - The effects of responsible drinking messages on attentional allocation and
      drinking behaviour.
AB  - AIMS: Four experiments were conducted to assess the acute impact of context and
      exposure to responsible drinking messages (RDMs) on attentional allocation and
      drinking behaviour of younger drinkers and to explore the utility of lab-based
      methods for the evaluation of such materials. METHODS: A simulated bar
      environment was used to examine the impact of context, RDM posters, and brief
      online responsible drinking advice on actual drinking behaviour. Experiments one
      (n = 50) and two (n = 35) comprised female non-problem drinkers, whilst
      Experiments three (n = 80) and 4 (n = 60) included a mixed-gender sample of non
      problem drinkers, recruited from an undergraduate student cohort. The Alcohol Use
      Disorders Identification Test (AUDIT) was used to assess drinking patterns.
      Alcohol intake was assessed through the use of a taste preference task. RESULTS:
      Drinking in a simulated bar was significantly greater than in a laboratory
      setting in the first two studies, but not in the third. There was a significant
      increase in alcohol consumption as a result of being exposed to RDM posters.
      Provision of brief online RDM reduced the negative impact of these posters
      somewhat; however the lowest drinking rates were associated with being exposed to
      neither posters nor brief advice. Data from the final experiment demonstrated a
      low level of visual engagement with RDMs, and that exposure to posters was
      associated with increased drinking. CONCLUSIONS: Poster materials promoting
      responsible drinking were associated with increased consumption amongst
      undergraduate students, suggesting that poster campaigns to reduce alcohol harms
      may be having the opposite effect to that intended. Findings suggest that further
      research is required to refine appropriate methodologies for assessing drinking
      behaviour in simulated drinking environments, to ensure that future public health
      campaigns of this kind are having their intended effect.

PMID- 25577317
TI  - Cementitious binders from activated stainless steel refining slag and the effect
      of alkali solutions.
AB  - With an aim of producing high value cementitious binder, stainless steel refining
      slag containing a high amount of CaO in gamma-dicalcium silicate form was
      activated with NaOH and Na-silicate as well as KOH and K-silicate solutions,
      followed by steam curing at 80  degrees C. Higher levels of alkali-silicate in
      the activating solution resulted in higher cumulative heat suggesting accelerated
      reaction kinetics. With respect to compressive strength, higher levels of alkali
      silicate resulted in higher strength and the mortars with Na activator were found
      to have higher early strength than the ones with K activator. The long term
      strength was found to be similar, regardless of the alkali metal.
      Thermogravimetric, QXRD and FTIR analyses showed an increase in the amount of
      reaction products (C-S-H type) over time, further confirming the reactivity of
      the crystalline slag. Batch leaching results showed lower leaching of heavy
      metals and metalloids with K activator compared to the Na activator. These
      results demonstrate that the alkali type and the ratio of hydroxide to silicates
      have a significant impact on the hydration and mechanical strength development of
      the stainless steel slag. The above findings can aid in the recycling and
      valorization of these type of slags which otherwise end up landfilled.

PMID- 25577318
TI  - Simple surface foam application enhances bioremediation of oil-contaminated soil
      in cold conditions.
AB  - Landfarming of oil-contaminated soil is ineffective at low temperatures, because
      the number and activity of micro-organisms declines. This study presents a simple
      and versatile technique for bioremediation of diesel-contaminated soil, which
      involves spraying foam on the soil surface without additional works such as
      tilling, or supply of water and air. Surfactant foam containing psychrophilic oil
      degrading microbes and nutrients was sprayed twice daily over diesel-contaminated
      soil at 6  degrees C. Removal efficiencies in total petroleum hydrocarbon (TPH)
      at 30 days were 46.3% for landfarming and 73.7% for foam-spraying. The first
      order kinetic biodegradation rates for landfarming and foam-spraying were
      calculated as 0.019 d(-1) and 0.044 d(-1), respectively. Foam acted as an
      insulating medium, keeping the soil 2  degrees C warmer than ambient air. Sprayed
      foam was slowly converted to aqueous solution within 10-12h and infiltrated the
      soil, providing microbes, nutrients, water, and air for bioaugmentation.
      Furthermore, surfactant present in the aqueous solution accelerated the
      dissolution of oil from the soil, resulting in readily biodegradable aqueous
      form. Significant reductions in hydrocarbon concentration were simultaneously
      observed in both semi-volatile and non-volatile fractions. As the initial soil
      TPH concentration increased, the TPH removal rate of the foam-spraying method
      also increased.

PMID- 25577319
TI  - Comparative cytotoxicity and accumulation of Roxarsone and its photodegradates in
      freshwater Protozoan Tetrahymenathermophila.
AB  - Roxarsone (ROX) remains to be as an organoarsenical feed additive used widely in
      developing countries. However, most of the ROX is excreted unchanged in manure,
      which could be readily photodegraded into inorganic arsenic derivatives. In this
      study, the comparative cytotoxicity and arsenic accumulation were evaluated after
      the exposure of Tetrahymenathermophila (T. thermophila) cell model to ROX and its
      photodegradates. The cytotoxic effects were estimated according to the relevant
      cell growth curves, morphologies and MTT assays. The 36 h median effective
      concentrations for ROX and its photodegradates at various photolysis times (10,
      20, and 30 min) are 39.0, 2.08, 1.88, and 1.82 mg (total arsenic) L(-1),
      respectively. In parallel, the cellular arsenic uptakes were determined by
      hydride generation-atomic fluorescence spectrometry. Phospholipid layer as basic
      membrane structure was mimicked to assess the correlation between membrane
      permeability and cytotoxicity. The biocompatibility of ROX was dependent on its
      tendency to interact with cell membrane while the cytotoxicity was induced by the
      trans-membrane of the inorganic arsenic species present in the photodegradates of
      ROX. Furthermore, the photodegradates of ROX-associated alterations of
      intracellular protein profiles were analyzed using a proteomic approach. Overall,
      the significance was clarified that the control of arsenic emission caused by the
      application of ROX needs to be imposed.

PMID- 25577320
TI  - Arsenic accumulation and speciation in rice grains influenced by arsenic
      phytotoxicity and rice genotypes grown in arsenic-elevated paddy soils.
AB  - Rice consumption is a major route of As exposure to human for the population of
      worldwide. This study investigates the effect of phytotoxicity and rice genotypes
      on the content and speciation of As in rice grains grown in different levels of
      As-elevated paddy soils from Taiwan. Three levels of As-elevated soils and six
      rice genotypes commonly planted in Taiwan were used for this study. The results
      indicate that As contents in grains of rice is not proportional to soil As
      concentrations and they were equal or higher in indica genotypes than japonica
      genotypes used in this study. It was also found that the As phytotoxicity not
      only reducing the grain yields but also the As concentrations in grain of rice.
      The predominant As species found in rice grains were dimethylarsinic acid (DMA)
      and arsenite. The concentrations of DMA increased with total As concentrations,
      wherggeas the arsenite remained in a narrow range from 0.1 to 0.3 mg kg(-1).
      Because of the lower toxicity of DMA than inorganic As species, the health risks
      may not be increased through consumption of rice even when total As content in
      the grains is increased.

PMID- 25577321
TI  - Toxic and inhibitory effects of trichloroethylene aerobic co-metabolism on phenol
      grown aerobic granules.
AB  - Aerobic granule, a form of microbial aggregate, exhibits good potential in
      degrading toxic and recalcitrant substances. In this study, the inhibitory and
      toxic effects of trichloroethylene (TCE), a model compound for aerobic co
      metabolism, on phenol-grown aerobic granules were systematically studied, using
      respiratory activities after exposure to TCE as indicators. High TCE
      concentration did not exert positive or negative effects on the subsequent
      endogenous respiration rate or phenol dependent specific oxygen utilization rate
      (SOUR), indicating the absence of solvent stress and induction effect on phenol
      hydroxylase. Phenol-grown aerobic granules exhibited a unique response to TCE
      transformation product toxicity, that small amount of TCE transformation enhanced
      the subsequent phenol SOUR. Granules that had transformed between 1.3 and 3.7 mg
      TCE gSS(-1) showed at most 53% increase in the subsequent phenol SOUR, and only
      when the transformation exceeded 6.6 mg TCE gSS(-1) did the SOUR dropped below
      that of the control. This enhancing effect was found to sustain throughout
      several phenol dosages, and TCE transformation below the toxicity threshold also
      lessened the granules' sensitivity to higher phenol concentration. The unique
      toxic effect was possibly caused by the granule's compact structure as a
      protection barrier against the diffusive transformation product(s) of TCE co
      metabolism.

PMID- 25577323
TI  - Compulsory private complementary health insurance offered by employers in France:
      implications and current debate.
AB  - In January 2013, within the framework of a National Inter-professional Agreement
      (NIA), the French government required all employers (irrespective of the size of
      their business) to offer private complementary health insurance to their
      employees from January 2016. The generalization of group complementary health
      insurance to all employees will directly affect insurers, employers and
      employees, as well as individuals not directly concerned (students, retirees,
      unemployed and civil servants). In this paper, we present the issues raised by
      this regulation, the expected consequences and the current debate around this
      reform. In particular, we argue that this reform may have adverse effects on
      equity of access to complementary health insurance in France, since the risk
      structure of the market for individual health insurance will change, potentially
      increasing inequalities between wage-earners and others. Moreover, tax exemptions
      given to group contracts are problematic because public funds used to support
      these contracts can be higher at individual level for high-salary individuals
      than those allocated to improve access for the poorest. In response to the
      criticism and with the aim of ensuring equity in the system, the government
      decided to reconsider some of the fiscal advantages given to group contracts, to
      enhance programs and aids dedicated to the poorest and to redefine an overall
      context of incentives. 

PMID- 25577322
TI  - An exploratory qualitative assessment of self-reported treatment outcomes and
      satisfaction among patients accessing an innovative voluntary drug treatment
      centre in Malaysia.
AB  - BACKGROUND: In Malaysia, compulsory drug detention centres (CDDCs) hold suspected
      drug users for two years without adjudication. Acute detoxification without
      healthcare access has been documented. CDDCs are criticized globally due to
      ineffectiveness in treating addiction and human rights violations. In response,
      the Malaysian government began transitioning these facilities into voluntary drug
      treatment centres known as "Cure and Care" (C&C) centres that embrace a holistic
      treatment-based approach to drug addiction rehabilitation. METHODS: An
      explorative qualitative study was undertaken to explore patient perspectives and
      satisfaction regarding treatment and services at the new Cure and Care centre in
      Kota Bharu, Malaysia. A convenience sample of 20 patients was recruited to
      participate in semi-structured in-depth interviews. Content analysis was used to
      identify the salient themes. RESULTS: Patients identified methadone treatment,
      psychosocial programs, religious instruction, and recreational activities as
      important factors contributing to treatment success for addressing both health
      and addiction needs. Though many had previously been in a CDDC, adherence to
      treatment in the C&C centre was perceived to be facilitated by the degree of
      social support, the voluntary nature and the array of new programs available for
      selection. CONCLUSION: C&Cs represents a dramatic shift in the Malaysian
      government's approach to drug addiction. Our findings demonstrate positive
      patient experiences associated with the holistic treatment-based approach of
      these centres. This exploratory study provides additional evidence to document
      this ongoing policy transition and may guide continued expansion of new holistic
      drug treatment programs across the country.

PMID- 25577324
TI  - Rapid screening methods for beta-emitters in food samples.
AB  - In case of a nuclear emergency, many samples need to be measured in a short time
      period. Therefore, it is of vital importance to have a quick and reliable
      (screening)method. Most methods to determine total beta activity are time
      consuming because of extensive sample preparation, such as ashing. In this
      article three different rapid screening methods for beta emitting nuclides in
      agriculture, livestock and fishery products were tested and compared to each
      other, and to an accurate but more time consuming reference method. The goal was
      to find the method with the optimal trade-off between accuracy, speed and minimal
      detectable activity (MDA). All of the methods rely on liquid scintillation
      counting (LSC) or Cerenkov counting, and differ mainly in sample preparation. For
      matrices with little or no colour, the direct LSC-method is the most accurate and
      fastest option, while for darker coloured samples this method is not suitable
      because of high colour quenching. For such samples, two additional methods using
      a microwave digestion during sample preparation, produced good results. 

PMID- 25577325
TI  - Alterations of neurotransmitter norepinephrine and gamma-aminobutyric acid
      correlate with murine behavioral perturbations related to bisphenol A exposure.
AB  - AIM: Humans are commonly exposed to endocrine-disrupting chemical bisphenol A
      (BPA), giving rise to concern over the psychobehavioral effects of BPA. The aim
      of this study was to investigate the effects of prenatal and lactational BPA
      exposure on neurotransmitters, including norepinephrine (NE), gamma-aminobutyric
      acid (GABA) and glutamate (Glu), and to assess the association with behavioral
      phenotypes. METHODS: C57BL/6J mice were orally administered with BPA (500
      MUg/bwkg/day) or vehicle daily from embryonic day 0 to postnatal week 3 (P3W),
      through their dams. The IntelliCage behavioral experiments were conducted from
      P11W to P15W. At around P14-16W, NE, GABA and Glu levels in nine brain regions
      were measured by high performance liquid chromatography. Furthermore, the
      associations between the neurotransmitter levels and the behavioral indices were
      statistically analyzed. RESULTS: In females exposed to BPA, the GABA and Glu
      levels in almost all regions, and the NE levels in the cortex, hypothalamus and
      thalamus were higher than those in the controls. In males exposed to BPA, the
      GABA levels in the amygdala and hippocampus showed lower values, while Glu levels
      were higher in some regions, compared with the controls. In regard to the
      associations, the number of "diurnal corner visits without drinking" was
      correlated with the NE levels in the cortex and thalamus in females. The
      "nocturnal corner visit duration without drinking" was correlated with the GABA
      level in the hippocampus in males. CONCLUSION: These results suggest that
      prenatal and lactational exposure to low doses of BPA might modulate the NE, GABA
      and Glu systems, resulting in behavioral alterations.

PMID- 25577327
TI  - Survey of Cochrane protocols found methods for data extraction from figures not
      mentioned or unclear.
AB  - OBJECTIVES: To analyze whether protocols of Cochrane systematic reviews address
      data extraction from figures in included trials. STUDY DESIGN AND SETTING:
      Protocols of Cochrane systematic reviews published between May 2013 and May 2014
      were screened by two authors independently, and the following data were
      collected: date of protocol publication, country of authors' origin, number of
      authors, number of affiliated institutions, Cochrane review group, whether the
      protocol contains description about data extraction from figures, method of data
      extraction from figures, and literature reference for a method of data extraction
      from figures. RESULTS: Among 589 protocols, 33 (5.6%) mentioned data extraction
      from figures in Methods section. Only one protocol specified that computer
      software will be used for data extraction from figures, one specifically
      indicated that data from figures will not be used, few stated estimation or
      approximation, whereas others did not provide any description of methodology for
      data extraction from figures. CONCLUSION: Very few protocols of Cochrane
      systematic reviews mention data extraction from figures, and even when mentioned,
      methods for data extraction are unclear. Methodology for data extraction from
      figures should be incorporated into the Cochrane Handbook and new methodological
      standards for Cochrane systematic reviews.

PMID- 25577326
TI  - [Initial experience in intraoperative radiolocalization of the parathyroid
      adenoma with freehand SPECT and comparative assessment with portable gamma
      camera].
AB  - Initial experience is presented by using freehand SPECT in the intraoperative
      radiolocalization of a parathyroid adenoma in 2 patients, one which was
      mediastinal. There is only one previous publication including 3 patients with
      parathyroid adenomas in usual parathyroid localizations. We also report for the
      first time a comparative assessment of results with portable gammacamera during
      the same surgery. In the operating room, we obtained images with portable gamma
      camera and 3 D reconstruction with freehand SPECT from 15 min after iv injection
      of 5 mCi of (99m)Tc-MIBI. Both devices enabled the 2 adenomas to be detected
      intraoperatively, as well as checking activity of the excised gland and absence
      of significant uptake in surgical bed, with confirmation by intraoperative pre
      postsurgical PTH levels, pathology and clinical follow-up for 10 months. Both
      devices accurately located the parathyroid adenomas intraoperatively, as well as
      confirmation of their extirpation, but freehand SPECT provided additional
      information of adenoma depth (mm) from the skin border, very useful for minimally
      invasive radio-guided surgery.

PMID- 25577328
TI  - Amaranth peptides from simulated gastrointestinal digestion: antioxidant activity
      against reactive species.
AB  - We evaluated the capacity of simulated gastrointestinal digests or alcalase
      hydrolysates of protein isolates from amaranth to scavenge diverse
      physiologically relevant reactive species. The more active hydrolysate was
      obtained with the former method. Moreover, a prior alcalase treatment of the
      isolate followed by the same simulated gastrointestinal digestion did not improve
      the antioxidant capacity in any of the assays performed and even produced a
      negative effect under some conditions. Gastrointestinal digestion produced a
      strong increment in the scavenging capacity against peroxyl radicals (ORAC
      assay), hydroxyl radicals (ESR-OH assay), and peroxynitrites; thus decreasing the
      IC50 values to approximately 20, 25, and 20%, respectively, of the levels
      attained with the nonhydrolyzed proteins. Metal chelation (HORAC assay) also
      enhanced respect to isolate levels, but to a lesser extent (decreasing IC50
      values to only 50%). The nitric-oxide- and superoxide-scavenging capacities of
      the digests were not relevant with respect to the methodologies used. The
      gastrointestinal digests from amaranth proteins acted against reactive species by
      different mechanisms, thus indicating the protein isolate to be a potential
      polyfunctional antioxidant ingredient.

PMID- 25577329
TI  - Use of baru (Brazilian almond) waste from physical extraction of oil to produce
      gluten free cakes.
AB  - The extraction of oil from baru almonds produces a waste that carries part of
      their nutritional qualities and antioxidants. It can be used to produce partially
      deffated baru flour (PDBF). We aimed to evaluate the applicability of PDBF and
      the effect of the addition of xanthan gum (XG) to produce gluten free cakes.
      Cakes were prepared with 100% wheat flour (WF cake) and with 100% PDBF and four
      different levels of XG (0%-PDBF cake, 0.1%-X1, 0.2%-X2 and 0.3%-X3 cakes), and
      evaluated for composition, antioxidants, moisture, specific volume, texture and
      sensory acceptance. PDBF cakes showed lower carbohydrate values, but higher
      protein, lipids, calories and antioxidant contents. They were rich in fiber, as
      well as iron, zinc and copper. The replacement of WF by PDBF resulted in an
      increased hardness and adhesiveness and a decreased cohesiveness, elasticity and
      moisture. Chewiness of X2 cake was similar to that of WF cake. X2 and X3 cakes
      showed specific volume closer to that of WF cake. No difference was found among
      the treatments for texture and appearance acceptances. Flavor of X2 and X3 cakes
      were more accepted than WF cake. Acceptance of all cakes were in the liking
      region of hedonic scale. PBDF associated to XG is a feasible option to substitute
      WF in gluten free cake, improving its nutritional quality.

PMID- 25577330
TI  - Plant lipid environment and membrane enzymes: the case of the plasma membrane H+
      ATPase.
AB  - Several lipid classes constitute the universal matrix of the biological
      membranes. With their amphipathic nature, lipids not only build the continuous
      barrier that confers identity to every cell and organelle, but they are also
      active actors that modulate the activity of the proteins immersed in the lipid
      bilayer. The plasma membrane H(+)-ATPase, an enzyme from plant cells, is an
      excellent example of a transmembrane protein whose activity is influenced by the
      hydrophilic compartments at both sides of the membrane and by the hydrophobic
      domains of the lipid bilayer. As a result, an extensive documentation of the
      effect of numerous amphiphiles in the enzyme activity can be found. Detergents,
      membrane glycerolipids, and sterols can produce activation or inhibition of the
      enzyme activity. In some cases, these effects are associated with the lipids of
      the membrane bulk, but in others, a direct interaction of the lipid with the
      protein is involved. This review gives an account of reports related to the
      action of the membrane lipids on the H(+)-ATPase activity. 

PMID- 25577332
TI  - De novo tacrolimus-induced thrombotic microangiopathy in the early stage after
      renal transplantation successfully treated with conversion to everolimus.
AB  - BACKGROUND: Calcineurin inhibitor (CNI)-induced thrombotic microangiopathy (TMA)
      is a rare complication after renal transplantation. It may be difficult to
      distinguish from CNI toxicity and acute antibody-mediated rejection (AMR). Its
      clinical presentation may vary from isolated localised forms up to catastrophic
      systemic presentations. CASE: We report a case of tacrolimus-induced TMA soon
      after renal transplantation in an 11-year-old boy who received his second renal
      transplantation. His first graft was lost because of AMR. On day 12 after his
      second renal transplantation, his renal function started worsening and a kidney
      biopsy was performed, which showed histopathological signs of TMA. The diagnosis
      of tacrolimus-induced TMA was established after excluding AMR and other causes of
      de novo TMA. Genetic complement investigation disclosed two complement factor H
      risk polymorphisms as possible modifiers of TMA emergence. Treatment was based on
      replacing tacrolimus with everolimus, with a subsequent normalisation of renal
      function. CONCLUSION: A prompt diagnosis of de novo TMA by early allograft biopsy
      is essential for the allograft outcome and genetic investigations for possible
      complement abnormalities are reasonable, not only for patients with a systemic
      aspect of their post-transplant TMA. Replacing tacrolimus with everolimus
      effectively controlled the TMA and stabilised renal function in our patient.

PMID- 25577331
TI  - Current progress towards the metabolic engineering of plant seed oil for hydroxy
      fatty acids production.
AB  - KEY MESSAGE: Hydroxy fatty acids produced in plant seed oil are important
      industrial material. This review focuses on the use of metabolic engineering
      approaches for the production of hydroxy fatty acids in transgenic plants.
      Vegetable oil is not only edible but can also be used for industrial purposes.
      The industrial demand for vegetable oil will increase with the continued
      depletion of fossil fuels and ensuing environmental issues such as climate
      change, caused by increased carbon dioxide in the air. Some plants accumulate
      high levels of unusual fatty acids in their seeds, and these fatty acids (FAs)
      have properties that make them suitable for industrial applications. Hydroxy
      fatty acids (HFAs) are some of the most important of these industrial FAs. Castor
      oil is the conventional source of HFA. However, due to the presence of toxin
      ricin in its seeds, castor is not cultivated on a large scale. Lesquerella is
      another HFA accumulator and is currently being developed as a new crop for a safe
      source of HFAs. The mechanisms of HFA synthesis and accumulation have been
      extensively studied using castor genes and the model plant Arabidopsis. HFAs
      accumulated to 17% in the seed oil of Arabidopsis expressing a FA hydroxylase
      gene from castor (RcFAH12), but its seed oil content and plant growth decreased.
      When RcFAH12 gene was coexpressed with additional castor gene(s) in Arabidopsis,
      ~30% HFAs were accumulated and the seed oil content and plant growth was almost
      restored to the wild-type level. Further advancement of our understanding of
      pathways, genes and regulatory mechanisms underlying synthesis and accumulation
      of HFAs is essential to developing and implementing effective genetic approaches
      for enhancing HFA production in oilseeds.

PMID- 25577333
TI  - Spontaneous periodic hypothermia in the postoperative phase of a brain tumor of
      the third ventricle.

PMID- 25577334
TI  - Investigation on the interactions of scutellarin and scutellarein with bovine
      serum albumin using spectroscopic and molecular docking techniques.
AB  - The binding abilities of scutellarin (Scu) and scutellarein (Scue) with bovine
      serum albumin (BSA) were investigated using equilibrium dialysis, high
      performance liquid chromatography, fluorescence spectroscopy, competitive site
      marker and molecular docking. The results showed that the average protein binding
      ratios of Scu and Scue with BSA were (79.85 +/- 1.83) and (85.49 +/- 1.21) %
      respectively. Under simulated physiological conditions, the fluorescence data
      indicated that Scu and Scue bound with BSA through a static mechanism. The
      thermodynamic parameters indicated that the interactions of Scu-BSA and Scue-BSA
      mainly occurred by van der Waals forces and hydrogen bonds and it was easier for
      Scue to bind with BSA than Scu, indicating that the glucuronic acid molecule in
      Scu decreased the binding affinity. Site competitive marker experiments showed
      that the binding sites of Scu and Scue mainly located within the sub-domain IIA
      of BSA. Furthermore, molecular docking studies indicated that one BSA could bind
      three Scue, while one BSA could carry only two Scu. All these results clearly
      indicated the interactions of Scu and Scue with BSA, which will lay the
      foundation for further research to determine the pharmacology and
      pharmacodynamics of Scu and Scue for treating ischemic cerebrovascular disease.

PMID- 25577335
TI  - PF2405, standardized fraction of Scutellaria baicalensis, ameliorates colitis in
      vitro and in vivo.
AB  - Standardized extraction procedures for herb are as important as their
      authentication to maintain their quality and ensure their safe use. We had
      prepared a standardized and purified Scutellaria baicalensis Georgi extract,
      PF2405, which was enriched with three major components, baicalein, oroxylin A and
      wogonin. In the present study, we investigated the potential anti-inflammatory
      effects of PF2405 in vitro and in two different experimental animal models of
      inflammatory bowel disease. Effect of PF2405 studied in tumor necrosis factor
      (TNF)-alpha-induced HT-29 cells in vitro. In vivo experimental colitis models
      were induced by administration of trinitrobenzene sulfonic acid (TNBS) or dextran
      sulfate sodium (DSS). PF2405 (50 MUg/ml) decreased TNF-alpha-induced
      cyclooxygenase (COX)-2 expressions through inhibition of phosphorylation of c-Jun
      N-terminal kinases and p38 mitogen-activated protein kinase in HT-29 cells.
      Combination of baicalein (20 MUg/ml), oroxylin A (8 MUg/ml), and wogonin (2
      MUg/ml) markedly inhibits TNF-alpha-induced COX-2 expression when compared with
      individual components. PF2405 (25 mg/kg b.w.) treatment significantly reduced
      histopathological severity; suppressed expression of COX-2, TNF-alpha, and
      interleukin-1beta in TNBS-induced mice. Moreover, PF2405 (25 mg/kg b.w.) has both
      potent preventive and therapeutic activities in DSS-induced colitis.
      Collectively, PF2405 shows prominent anti-inflammatory effect that can be used as
      a new therapeutic approach for intestinal inflammatory disorders.

PMID- 25577336
TI  - Mom Power: preliminary outcomes of a group intervention to improve mental health
      and parenting among high-risk mothers.
AB  - Maternal psychopathology and traumatic life experiences may adversely impact
      family functioning, the quality of the parent-child relationship and the
      attachment bond, placing the child's early social-emotional development at risk.
      Attachment-based parenting interventions may be particularly useful in decreasing
      negative outcomes for children exposed to risk contexts, yet high risk families
      frequently do not engage in programs to address mental health and/or parenting
      needs. This study evaluated the effects of Mom Power (MP), a 13-session parenting
      and self-care skills group program for high-risk mothers and their young children
      (age <6 years old), focused on enhancing mothers' mental health, parenting
      competence, and engagement in treatment. Mothers were referred from community
      health providers for a phase 1 trial to assess feasibility, acceptability, and
      pilot outcomes. At baseline, many reported several identified risk factors,
      including trauma exposure, psychopathology, poverty, and single parenthood.
      Ninety-nine mother-child pairs were initially recruited into the MP program with
      68 women completing and providing pre- and post-self-report measures assessing
      demographics and trauma history (pre-assessment only), maternal mental health
      (depression and post-traumatic stress disorder (PTSD)), parenting, and
      intervention satisfaction. Results indicate that MP participation was associated
      with reduction in depression, PTSD, and caregiving helplessness. A dose response
      relationship was evident in that, despite baseline equivalence, women who
      attended >=70 % of the 10 groups (completers; N = 68) improved on parenting and
      mental health outcomes, in contrast to non-completers (N = 12). Effects were most
      pronounced for women with a mental health diagnosis at baseline. The intervention
      was perceived as helpful and user-friendly. Results indicate that MP is feasible,
      acceptable, and holds promise for improving maternal mental health and parenting
      competence among high-risk dyads. Further research is warranted to evaluate the
      efficacy of MP using randomized controlled designs. 

PMID- 25577337
TI  - "I didn't know it was possible to feel that tired": exploring the complex
      bidirectional associations between maternal depressive symptoms and fatigue in a
      prospective pregnancy cohort study.
AB  - Depressive and fatigue symptoms are common health concerns for women in the
      postnatal period. Few studies have sought to investigate the role of fatigue in
      the development and maintenance of depressive symptoms. The aim of this paper was
      to examine the relationship between depressive symptoms and fatigue over the
      course of the first 4 years postpartum, in particular focusing on the extent to
      which fatigue at earlier time points predicted later depressive symptoms and vice
      versa. Data from over 1000 women participating in a longitudinal study of
      Australian women's physical and psychological health and recovery after
      childbirth were used. An autoregressive cross-lagged panel model was tested to
      assess the mutual influences of fatigue and depressive symptoms across five time
      points at 3, 6, 12 and 18 months postpartum, and at 4 years postpartum. A complex
      bidirectional relationship between fatigue and depressive symptoms from 3 months
      to 4 years postpartum was observed, where fatigue at earlier time points
      predicted depressive symptoms at later time points, and vice versa. The findings
      of this study suggest interventions targeting the prevention and management of
      fatigue may also confer some benefit in improving or preventing the development
      of depression symptoms in the early parenting period.

PMID- 25577338
TI  - Health services utilization of women following a traumatic birth.
AB  - This cohort study compared 262 women with high childbirth distress to 138 non
      distressed women. At 12 months, high distress women had lower health-related
      quality of life compared to non-distressed women (EuroQol five-dimensional (EQ
      5D) scale 0.90 vs. 0.93, p = 0.008), more visits to general practitioners (3.5
      vs. 2.6, p = 0.002) and utilized more additional services (e.g. maternal health
      clinics), with no differences for infants. Childbirth distress has lasting
      adverse health effects for mothers and increases health-care utilization. 

PMID- 25577339
TI  - Human-derived cathelicidin LL-37 directly activates mast cells to proinflammatory
      mediator synthesis and migratory response.
AB  - Cathelicidins, a family of antimicrobial peptides, are well known for their role
      in host defense, particularly against bacteria. Apart from direct killing of
      microbes through the membrane disruption, cathelicidins can also exert
      immunomodulatory effects on cells involved in inflammatory processes. Considering
      the important role of mast cells in inflammation, the aim of this study was to
      determine whether LL-37, human-derived cathelicidin, can induce mast cell
      activation. We have observed that LL-37 directly stimulates mast cell to
      degranulation and production of some proinflammatory cytokines, but fails to
      induce cysteinyl leukotriene generation and release. We have also documented that
      LL-37 acts as a strong mast cell chemoattractant. In intracellular signaling in
      mast cells activated by LL-37 participates PLC/A2 and, in part, MAPKs, and PI3K.
      In conclusion, our results indicate that cathelicidins may enhance antibacterial
      inflammatory response via attracting mast cell to pathogen entry site and via
      induction of mast cell-derived mediator release. 

PMID- 25577340
TI  - A clinical correlation of anti-DNA-AGE autoantibodies in type 2 diabetes mellitus
      with disease duration.
AB  - Nonenzymatic glycation of amino groups of DNA bases by reducing sugars can
      generate advanced glycation end products (AGEs). Cellular formation of AGEs under
      normal physiology is continuously scanned and removed by efficient system in the
      cells. However, excess formation and accumulation of AGEs may be cause or
      consequence of some human diseases. Mammalian DNA incubated with d-glucose for 28
      days at 37 degrees C showed structural changes in DNA as confirmed by UV,
      fluorescence, CD, melting temperature, S1 nuclease sensitivity and gel
      electrophoresis. Formation of DNA-AGE was confirmed by HPLC and LC-MS. Enzyme
      immunoassay and electrophoretic mobility shift assay of autoantibodies in type 2
      diabetes patients' sera with disease duration of 5-15 years exhibited
      significantly high binding with DNA-AGE as compared to patients with 1-5 years of
      disease duration. Autoantibodies against aberrant DNA-AGE may be important in the
      assessment of initiation/progression of secondary complications in type 2
      diabetes mellitus patients.

PMID- 25577341
TI  - The effect of ROCK on TNF-alpha-induced CXCL8 secretion by intestinal epithelial
      cell lines is mediated through MKK4 and JNK signaling.
AB  - Intestinal epithelial cells (IEC) play a role in mucosal inflammatory responses
      by producing important chemokines like CXCL8 when stimulated by TNF-alpha.
      Previously, we found that IEC cell lines required the Rho-associated kinase,
      ROCK, for CXCL8 responses after IL-1 stimulation. This study extends these
      findings by showing that inhibiting ROCK suppressed TNF-alpha-induced CXCL8
      secretion by Caco-2 and DLD1 colonic epithelial cell lines and CXCL8 mRNA levels
      in Caco-2 cells. RNAi knockdown experiments indicated that the inhibitory effect
      was mediated by ROCK2, and not ROCK1. Inhibiting ROCK had no effect on TNF
      stimulated IkappaBalpha phosphorylation and degradation or p38 MAPK
      phosphorylation indicating that ROCK plays no role in these signaling pathways.
      However, inhibiting ROCK suppressed TNF-induced phosphorylation of the p54 JNK
      isoform and phosphorylation of the upstream MKK4 kinase. These results suggest
      that ROCK is required for CXCL8 responses by TNF-stimulated IEC by affecting
      intracellular signaling through MKK4 and JNK. 

PMID- 25577342
TI  - Recombinant TB9.8 of Mycobacterium bovis Triggers the Production of IL-12 p40 and
      IL-6 in RAW264.7 Macrophages via Activation of the p38, ERK, and NF-kappaB
      Signaling Pathways.
AB  - The TB9.8 of Mycobacterium bovis can induce strong antigen-specific T-cell
      responses in proliferation assays and IFN-gamma assays. However, whether and how
      TB9.8 activates innate immune cells remain unclear. Therefore, recombinant
      protein TB9.8 (rTB9.8)-induced proinflammatory cytokine profile by RAW264.7 cells
      was investigated and the related signaling pathway was studied. Stimulation with
      rTB9.8 triggered RAW264.7 cells to produce IL-6 and IL-12 p40. In addition,
      rTB9.8 activated the mitogen-activated protein kinase (MAPK) cascade in RAW264.7
      cells by inducing the phosphorylation of extracellular signal-regulated kinase
      (ERK) and p38 kinase (p38) and also promoted nuclear translocation of
      phosphorylated p38 and ERK1/2. Furthermore, rTB9.8 activated nuclear factor
      kappaB (NF-kappaB) signaling pathway by inducing p65 translocation into the
      nucleus and the phosphorylation of IkappaBalpha in the cytosol. Blocking assays
      showed that specific inhibitors of ERK1/2, p38, and IkappaBalpha can
      significantly reduce the expression of IL-6 and IL-12 p40, which demonstrated
      that rTB9.8-mediated cytokine production is dependent on the activation of these
      kinases. Thus, this study demonstrates that rTB9.8 can activate RAW264.7 and
      trigger IL-6 and IL-12 p40 production via the ERK, p38, and NF-kappaB signaling
      pathways. 

PMID- 25577343
TI  - Selenium Deficiency Facilitates Inflammation Through the Regulation of TLR4 and
      TLR4-Related Signaling Pathways in the Mice Uterus.
AB  - Selenium (Se) is an essential nutritional trace element that affects the
      development and function of the reproductive system. Endometritis is a
      reproductive obstacle disease that can seriously reduce the reproductive capacity
      of animal. To study the effects of dietary Se deficiency on lipopolysaccharide
      (LPS)-induced mice endometritis, we generated a model of LPS-induced mice
      endometritis. The Se content in uterine tissues was detected by fluorescence
      spectrophotometry. The levels of tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1beta, and IL-6 were measured by enzyme-linked immunosorbent
      assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The
      extent of phosphorylation of IkappaBalpha, NF-kappaB p65, ERK, JNK, and p38 and
      the expression of Toll-like receptor 4 (TLR4) were detected with Western blots.
      The TLR4 messenger RNA (mRNA) was analyzed with qRT-PCR. The results indicated
      that dietary Se intake significantly influenced Se levels in uterine tissues. The
      Se-deficient mice model was successfully replicated, and Se deficiency
      exacerbated uterine tissue histopathology; increased the expression of TNF-alpha,
      IL-1beta, and IL-6; facilitated the activation of TLR4; and enhanced the
      phosphorylation of IkappaBalpha, p65, ERK, JNK, and p38 in LPS-induced mice
      endometritis. Also, the effects were inhibited by a supplement of Se. In
      conclusion, our studies demonstrated that Se deficiency makes mice uterus more
      prone to inflammation. An appropriate Se supplement could enhance the immune
      condition of the uterus. 

PMID- 25577344
TI  - Wear Particles Impair Antimicrobial Activity Via Suppression of Reactive Oxygen
      Species Generation and ERK1/2 Phosphorylation in Activated Macrophages.
AB  - Implant-related infection (IRI) is closely related to the local immunity of peri
      implant tissues. The generation of reactive oxygen species (ROS) in activated
      macrophages plays a prominent role in the innate immune response. In previous
      studies, we indicated that implant wear particles promote endotoxin tolerance by
      decreasing the release of proinflammatory cytokines. However, it is unclear
      whether ROS are involved in the damage of the local immunity of peri-implant
      tissues. In the present study, we assessed the mechanism of local
      immunosuppression using titanium (Ti) particles and/or lipopolysaccharide (LPS)
      to stimulate RAW 264.7 cells. The results indicate that the Ti particles induced
      the generation of a moderate amount of ROS through nicotinamide adenine
      dinucleotide phosphate oxidase-1, but not through catalase. Pre-exposure to Ti
      particles inhibited ROS generation and extracellular-regulated protein kinase
      activation in LPS-stimulated macrophages. These findings indicate that chronic
      stimulation by Ti particles may lead to a state of oxidative stress and
      persistent inflammation, which may result in the attenuation of the immune
      response of macrophages to bacterial components such as LPS. Eventually,
      immunosuppression develops in peri-implant tissues, which may be a risk factor
      for IRI. 

PMID- 25577345
TI  - Exploring a new serine protease from Cucumis sativus L.
AB  - Coagulation is an important physiological process in hemostasis which is
      activated by sequential action of proteases. This study aims to understand the
      involvement of aqueous fruit extract of Cucumis sativus L. (AqFEC) European burp
      less variety in blood coagulation cascade. AqFEC hydrolyzed casein in a dose
      dependent manner. The presence of protease activity was further confirmed by
      casein zymography which revealed the possible presence of two high molecular
      weight protease(s). The proteolytic activity was inhibited only by phenyl methyl
      sulphonyl fluoride suggesting the presence of serine protease(s). In a dose
      dependent manner, AqFEC also hydrolysed Aalpha and Bbeta subunits of fibrinogen,
      whereas it failed to degrade the gamma subunit of fibrinogen even at a
      concentration as high as 100 MUg and incubation time up to 4 h. AqFEC reduced the
      clotting time of citrated plasma by 87.65%. The protease and fibrinogenolytic
      activity of AqFEC suggests its possible role in stopping the bleeding and ensuing
      wound healing process.

PMID- 25577346
TI  - Enhanced production of nargenicin A(1) and generation of novel glycosylated
      derivatives.
AB  - Nargenicin A1, an antibacterial polyketide macrolide produced by Nocardia sp.
      CS682, was enhanced by increasing the pool of precursors using different sources.
      Furthermore, by using engineered strain Nocardia sp. ACC18 and supplementation of
      glucose and glycerol, enhancement was ~7.1 fold in comparison to Nocardia sp.
      CS682 without supplementation of any precursors. The overproduced compound was
      validated by mass spectrometry and nuclear magnetic resonance analyses. The novel
      glycosylated derivatives of purified nargenicin A1 were generated by efficient
      one-pot reaction systems in which the syntheses of uridine diphosphate (UDP)
      alpha-D-glucose and UDP-alpha-D-2-deoxyglucose were modified and combined with
      glycosyltransferase (GT) from Bacillus licheniformis. Nargenicin A1 11-O-beta- D
      glucopyranoside, nargenicin A1 18-O-beta-D-glucopyranoside, nargenicin A111 18-O
      beta-D- diglucopyranoside, and nargenicin 11-O-beta-D-2-deoxyglucopyranoside were
      generated. Nargenicin A1 11-O-beta-D-glucopyranoside was structurally elucidated
      by ultra-high performance liquid chromatography-photodiode array (UPLC-PDA)
      conjugated with high-resolution quantitative time-of-flight-electrospray
      ionization mass spectroscopy (HR-QTOF ESI-MS/MS), supported by one- and two
      dimensional nuclear magnetic resonance studies, whereas other nargenicin A1
      glycosides were characterized by UPLC-PDA and HR-QTOF ESI-MS/MS analyses. The
      overall conversion studies indicated that the one-pot synthesis system is a
      highly efficient strategy for production of glycosylated derivatives of compounds
      like macrolides as well. Furthermore, assessment of solubility indicated that
      there was enhanced solubility in the case of glycoside, although a substantial
      increase in activity was not observed. 

PMID- 25577348
TI  - Erratum to: Effect of Metal Ions and Redox Mediators on Decolorization of
      Synthetic Dyes by Crude Laccase from a Novel White rot Fungus Peniophora sp.
      (NFCCI-2131).

PMID- 25577347
TI  - Biochemical characterization of a thermostable adenosylmethionine synthetase from
      the archaeon Pyrococcus furiosus with high catalytic power.
AB  - Adenosylmethionine synthetase plays a key role in the biogenesis of the sulfonium
      compound S-adenosylmethionine, the principal widely used methyl donor in the
      biological methylations. We report here, for the first time, the characterization
      of adenosylmethionine synthetase from the hyperthermophilic archaeon Pyrococcus
      furiosus (PfMAT). The gene PF1866 encoding PfMAT was cloned and expressed, and
      the recombinant protein was purified to homogeneity. PfMAT shares 51, 63, and 82%
      sequence identity with the homologous enzymes from Sulfolobus solfataricus,
      Methanococcus jannaschii, and Thermococcus kodakarensis, respectively. PfMAT is a
      homodimer of 90 kDa highly thermophilic with an optimum temperature of 90 
      degrees C and is characterized by remarkable thermodynamic stability (Tm, 99 
      degrees C), kinetic stability, and resistance to guanidine hydrochloride-induced
      unfolding. The latter process is reversible as demonstrated by the analysis of
      the refolding process by activity assays and fluorescence measurements. Limited
      proteolysis experiments indicated that the proteolytic cleavage site is localized
      at Lys148 and that the C-terminal peptide is necessary for the integrity of the
      active site. PfMAT shows kinetic features that make it the most efficient
      catalyst for S-adenosylmethionine synthesis among the characterized MAT from
      Bacteria and Archaea. Molecular and structural characterization of PfMAT could be
      useful to improve MAT enzyme engineering for biotechnological applications.

PMID- 25577349
TI  - Biosynthesis of seven carbon-13 labeled Alternaria toxins including altertoxins,
      alternariol, and alternariol methyl ether, and their application to a multiple
      stable isotope dilution assay.
AB  - An unprecedented stable isotope dilution assay for the genotoxic altertoxins
      along with exposure data of consumers is presented to enable a first risk
      assessment of these Alternaria toxins in foods. Altertoxins were produced as the
      most abundant Alternaria toxins in a modified Czapek-Dox medium with a low level
      of glucose as the carbon source and ammonium sulfate as the sole nitrogen source.
      Labeled altertoxins were synthesized in the same way using [(13)C6]glucose.
      Moreover, labeled alternariol, alternariol methyl ether, altenuene, and
      alternuisol were biosynthesized in another modified medium containing
      [(13)C6]glucose and sodium [(13)C2]acetate. A stable isotope dilution LC-MS/MS
      method was developed and used for food analysis. For altertoxin I, altertoxin II,
      alterperylenol, alternariol, and alternariol methyl ether, the limits of
      detection ranged from 0.09 to 0.53 MUg kg(-1). The inter-/intra-day (n = 3 * 6)
      relative standard deviations of the method were below 13%, and the recoveries
      ranged between 96 and 109%. Among the various commercial food samples, some of
      the organic whole grains revealed low-level contamination with altertoxin I and
      alterperylenol, and paprika powder, which was heavily loaded with alternariol,
      alternariol methyl ether, and tentoxin, showed higher contamination level of
      altertoxin I and alterperylenol. Altertoxin II and III and stemphyltoxin III were
      not detectable. In addition, if the food was contaminated with altertoxins, it
      was likely to be co-contaminated with the other Alternaria toxins, but not
      necessarily vice versa. Maximum concentrations of altertoxin I and alterperylenol
      were detected in sorghum feed samples containing 43 and 58 MUg kg(-1),
      respectively. This was significantly higher than that in the measured food
      samples.

PMID- 25577350
TI  - Targeted metabolomics of the arachidonic acid cascade: current state and
      challenges of LC-MS analysis of oxylipins.
AB  - Quantification of eicosanoids and oxylipins derived from other polyunsaturated
      fatty acids in biological samples is crucial for a better understanding of the
      biology of these lipid mediators. Moreover, a robust and reliable quantification
      is necessary to monitor the effects of pharmaceutical intervention and diet on
      the arachidonic acid (AA) cascade, one of today's most relevant drug targets. Low
      (sub-nanomolar) concentrations and a large number of structurally similar
      analytes, including regioisomers, require high chromatographic resolution and
      selective and sensitive mass spectrometry analysis. Currently, reversed-phase
      liquid chromatography in combination with detection on sensitive triple
      quadrupole instruments, operating in selected reaction monitoring mode, is the
      main method of quantitative oxylipin analysis. A lack of standardized sample
      collection, handling, and preparation procedures, degradation of the analytes
      during sample preparation, and purity and availability of standards (internal
      standards) are the major problems of targeted metabolomics approaches for the AA
      cascade. Major challenges for instrumental analytical methods are the detection
      of esterified oxylipins, and separation and individual detection of oxylipin
      isomers. Solving these problems would help to further knowledge of the biology of
      lipid mediators, and is an important task for bio-analytical research. 

PMID- 25577351
TI  - Using MOOCs for teaching analytical chemistry: experience at University of Tartu.

PMID- 25577352
TI  - Determination of omega-6 and omega-3 PUFA metabolites in human urine samples
      using UPLC/MS/MS.
AB  - The omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) such as arachidonic
      acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are the
      precursors of various bioactive lipid mediators including prostaglandins,
      thromboxanes, leukotrienes, hydroxyeicosatetraenoic acid, isoprostanes, lipoxins,
      and resolvins (Rvs). These lipid mediators play important roles in various
      physiological and pathological processes. The quantitative determination of PUFA
      metabolites seems necessary for disease research and for developing biomarkers.
      However, there is a paucity of analytical methods for the quantification of omega
      6 and omega-3 PUFA metabolites-the specialized pro-resolving mediators (SPMs)
      present in the human urine. We developed a method for the quantification of omega
      6 and omega-3 PUFA metabolites present in human urine using ultra-performance
      liquid chromatography/tandem mass spectrometry (UPLC/MS/MS). The developed method
      shows good linearity, with a correlation coefficient >0.99 for all of the
      analytes. The validation results indicate that our method is adequately reliable,
      accurate, and precise. The method was successfully used to examine urine samples
      obtained from 43 healthy volunteers. We could identify 20 PUFA metabolites, and
      this is the first report of the quantitative determination of RvD1, 17(R)-RvD1,
      11-dehydro thromboxane B3, RvE2, and 5(S)-HETE in human urine. The urinary 8-iso
      PGF(2alpha) and PGE2 levels were significantly higher in the men smokers than in
      the men nonsmokers (p < 0.05). In this study, we developed an accurate, precise,
      and novel analytical method for estimating the omega-6 and omega-3 PUFA
      metabolites, and this is the first report that the SPMs derived from EPA and DHA
      are present in human urine.

PMID- 25577353
TI  - Lefetamine, a controlled drug and pharmaceutical lead of new designer drugs:
      synthesis, metabolism, and detectability in urine and human liver preparations
      using GC-MS, LC-MS(n), and LC-high resolution-MS/MS.
AB  - Lefetamine (N,N-dimethyl-1,2-diphenylethylamine, L-SPA) was marketed as an opioid
      analgesic in Japan and Italy. After being widely abused, it became a controlled
      substance. It seems to be a pharmaceutical lead for designer drugs because N
      ethyl-1,2-diphenylethylamine (NEDPA) and N-iso-propyl-1,2-diphenylethylamine
      (NPDPA) were confiscated by the German police. In contrast to these derivatives,
      metabolism and detectability of lefetamine were not studied yet. Therefore, phase
      I and II metabolism should be elucidated and correlated to the derivatives. Also
      the detectability using the authors' standard urine screening approaches (SUSA)
      needed to be checked. As lefetamine was commercially unavailable, it had to be
      synthesized first. For metabolism studies, a high dose of lefetamine was
      administered to rats and the urine samples worked up in different ways.
      Separation and analysis were achieved by gas chromatography-mass spectrometry (GC
      MS) and liquid chromatography-high resolution-tandem mass spectrometry (LC-HR
      MS/MS). In accordance with NEPDA and NPDPA, the following metabolic steps could
      be proposed: N-oxidation, N-dealkylation, mono- and bis-hydroxylation of the
      benzene ring, and hydroxylation of the phenyl ring only after N-dealkylation. The
      di-hydroxy metabolites were conjugated by methylation of one hydroxy group, and
      hydroxy metabolites by glucuronidation or sulfation. All initial metabolites
      could also be detected in human liver preparations. After a therapeutic
      lefetamine dose, the bis-nor, bis-nor-hydroxy, nor-hydroxy, nor-di-hydroxy
      metabolites could be detected using the authors' GC-MS SUSA and the nor-hydroxy
      glucuronide by the LC-MS(n) SUSA. Thus, an intake of lefetamine should be
      detectable in human urine assuming similar pharmacokinetics. 

PMID- 25577354
TI  - Field-flow fractionation coupled to ICP-MS: separation at the nanoscale, previous
      and recent application trends.
AB  - Since its introduction in the early 1990s, the on-line coupling of field-flow
      fractionation to inductively coupled plasma-mass spectrometry (FFF/ICP-MS) has
      evolved from a "niche" method into an established technique, especially in the
      field of natural-colloid analysis. Around the turn of the millennium engineered
      nanomaterials became prominent in research as a result of new properties, and in
      recent years FFF/ICP-MS has been revealed to be a promising tool for their
      analysis. Given the beneficial properties of this technique (e.g., no stationary
      phase, high separation power, multi-elemental capabilities, and high sensitivity)
      further applications, especially in the field of biomolecule analysis, will be
      discovered in the near future, and FFF will evolve further as a complementary
      tool to well-established chromatographic techniques (e.g. high-performance liquid
      chromatography, size-exclusion chromatography). The focus of this article is on
      recent application trends of FFF/ICP-MS, revealing the applicability of this
      technique within several fields of research, especially natural colloids and
      engineered nanoparticles. Possible future application trends, based on the
      author's opinion, are outlined in the "Concluding remarks and outlook" section. 

PMID- 25577355
TI  - Molecularly imprinted microspheres synthesized by a simple, fast, and universal
      suspension polymerization for selective extraction of the topical anesthetic
      benzocaine in human serum and fish tissues.
AB  - A simple, fast, and universal suspension polymerization method was used to
      synthesize the molecularly imprinted microspheres (MIMs) for the topical
      anesthetic benzocaine (BZC). The desired diameter (10-20 MUm) and uniform
      morphology of the MIMs were obtained easily by changing one or more of the
      synthesis conditions, including type and amount of surfactant, stirring rate, and
      ratio of organic to water phase. The MIMs obtained were used as a molecular
      imprinting solid-phase-extraction (MISPE) material for extraction of BZC in human
      serum and fish tissues. The MISPE results revealed that the BZC in these
      biosamples could be enriched effectively after the MISPE operation. The
      recoveries of BZC on MIMs cartridges were higher than 90% (n = 3). Finally, an
      MISPE-HPLC method with UV detection was developed for highly selective extraction
      and fast detection of trace BZC in human serum and fish tissues. The developed
      method could also be used for the enrichment and detection of BZC in other
      complex biosamples.

PMID- 25577356
TI  - Development and characterization of magnetic molecularly imprinted polymers for
      the selective enrichment of endocrine disrupting chemicals in water and milk
      samples.
AB  - Analyses of four endocrine disrupting chemicals (EDCs) in water and milk samples
      were undertaken by using magnetic molecularly imprinted polymers (MMIPs). These
      were prepared via the surface molecular imprinting technique using super
      paramagnetic core-shell nanoparticle as support. Diethylstilbestrol (DES), which
      is a typical EDC, was employed as the template molecule. The obtained MMIPs were
      characterized using transmission electron microscope, Fourier transform infrared,
      X-ray diffraction, and vibrating sample magnetometer. Accordingly, the adsorption
      capacity and selectivity of prepared MMIPs were investigated. The binding
      isotherms were obtained for DES and fitted by the Freundlich isotherm model. A
      corresponding analytical method to determine four EDCs was developed. The
      recoveries of the spiked samples in pond water and pure milk range from 67.8 to
      93.2% and from 65.3 to 92.5%, respectively. Coupled with high-performance liquid
      chromatography analysis, the prepared MMIPs were successfully applied to the
      analysis of EDCs in water and milk samples.

PMID- 25577357
TI  - Analysis of plasticizers in poly(vinyl chloride) medical devices for infusion and
      artificial nutrition: comparison and optimization of the extraction procedures, a
      pre-migration test step.
AB  - Medical devices (MDs) for infusion and enteral and parenteral nutrition are
      essentially made of plasticized polyvinyl chloride (PVC). The first step in
      assessing patient exposure to these plasticizers, as well as ensuring that the
      MDs are free from di(2-ethylhexyl) phthalate (DEHP), consists of identifying and
      quantifying the plasticizers present and, consequently, determining which ones
      are likely to migrate into the patient's body. We compared three different
      extraction methods using 0.1 g of plasticized PVC: Soxhlet extraction in diethyl
      ether and ethyl acetate, polymer dissolution, and room temperature extraction in
      different solvents. It was found that simple room temperature chloroform
      extraction under optimized conditions (30 min, 50 mL) gave the best separation of
      plasticizers from the PVC matrix, with extraction yields ranging from 92 to 100%
      for all plasticizers. This result was confirmed by supplemented Fourier transform
      infrared spectroscopy-attenuated total reflection (FTIR-ATR) and gravimetric
      analyses. The technique was used on eight marketed medical devices and showed
      that they contained different amounts of plasticizers, ranging from 25 to 36% of
      the PVC weight. These yields, associated with the individual physicochemical
      properties of each plasticizer, highlight the need for further migration studies.

PMID- 25577358
TI  - Nanometer-sized materials for solid-phase extraction of trace elements.
AB  - This review presents a comprehensive update on the state-of-the-art of nanometer
      sized materials in solid-phase extraction (SPE) of trace elements followed by
      atomic-spectrometry detection. Zero-dimensional nanomaterials (fullerene), one
      dimensional nanomaterials (carbon nanotubes, inorganic nanotubes, and nanowires),
      two-dimensional nanomaterials (nanofibers), and three-dimensional nanomaterials
      (nanoparticles, mesoporous nanoparticles, magnetic nanoparticles, and dendrimers)
      for SPE are discussed, with their application for trace-element analysis and
      their speciation in different matrices. A variety of other novel SPE sorbents,
      including restricted-access sorbents, ion-imprinted polymers, and metal-organic
      frameworks, are also discussed, although their applications in trace-element
      analysis are relatively scarce so far. 

PMID- 25577359
TI  - Cross-platform metabolic profiling: application to the aquatic model organism
      Lymnaea stagnalis.
AB  - The freshwater pond snail Lymnaea stagnalis is used in several studies on
      molecular and behavioral neurobiology and ecotoxicology showing its successful
      application as a model organism. In the present study, a cross-platform
      metabolomic approach has been evaluated to characterize the organ molecular
      phenotypes of L. stagnalis central nervous system (CNS), digestive gland (DG),
      and albumen gland (AG). Two types of tissue disruption methods were evaluated of
      which beads beating was the preferred method. To obtain a broad picture of the
      hydrophilic and lipophilic metabolome, two complementary analytical platforms
      have been employed: liquid chromatography (LC) and gas chromatography (GC)
      coupled to high-resolution mass spectrometry. Furthermore, to increase the power
      to separate small polar metabolites, hydrophilic interaction liquid
      chromatography (HILIC) was applied. The analytical platform performances have
      been evaluated based on the metabolome coverage, number of molecular features,
      reproducibility, and multivariate data analysis (MVDA) clustering. This
      multiplatform approach is a starting point for future global metabolic profiling
      applications on L. stagnalis. 

PMID- 25577360
TI  - Integrated comparative metabolite profiling via MS and NMR techniques for Senna
      drug quality control analysis.
AB  - Senna alexandrina Mill (Cassia acutifolia and Cassia angustifolia) are used for
      the laxative medicine Senna. Leaves and pods from two geographically different
      sources were distinguished from each other via proton nuclear magnetic resonance
      (1H-NMR) and ultra performance liquid chromatography-mass spectrometry (UPLC-MS)
      analysis. Under optimized conditions, we were able to simultaneously quantify and
      identify 107 metabolites including 21 anthraquinones, 24 bianthrones (including
      sennosides), 5 acetophenones, 25 C/O-flavonoid conjugates, 5 xanthones, 3
      naphthalenes, 2 further phenolics, and 9 fatty acids. Principal component
      analysis (PCA) and hierarchical clustering analysis (HCA) were used to define
      both similarities and differences among samples. For sample classification based
      on tissue type (leaf and pod), both UPLC-MS and NMR were found to be more
      effective in separation than on geographical origin. Results reveal that the
      amounts of the major classes of bioactives in Senna, i.e., flavonoids and
      sennosides, varied significantly among organs. Leaves contained more flavonoids
      and omega-3 fatty acids but fewer benzophenone derivatives than pods. In
      contrast, pods were more enriched in bianthrones (sennosides). PCA analysis was
      found to be equally effective in predicting the origin of the commercial Senna
      preparation using NMR and/or UPLC-MS datasets. Furthermore, a selection of six so
      far uninvestigated Senna species were analyzed by UPLC-MS. Results revealed that
      the Senna alata leaf in terms of secondary metabolite composition is the most
      closely related species to S. alexandrina Mill, showing the highest levels of the
      anthraquinone "rhein" and flavonoid conjugates. To the best of our knowledge,
      this study provides the first approach utilizing both UPLC-MS and NMR to reveal
      secondary metabolite compositional differences among Senna species. 

PMID- 25577361
TI  - Tag-femtosecond laser-induced breakdown spectroscopy for the sensitive detection
      of cancer antigen 125 in blood plasma.
AB  - Successful treatment of cancers requires detecting early signs of the disease.
      One promising way to approach this is to develop minimally invasive tests for the
      sensitive and specific detection of biomarkers in blood. Irrespective of the
      detection approach one uses, this remains a challenging task because biomarkers
      are typically present in low concentrations and there are signals that interfere
      strongly with prevailing compounds of human fluids. In this paper, we show that
      elemental encoded particle assay coupled with femtosecond laser-induced breakdown
      spectroscopy for simultaneous multi-elemental analysis can significantly improve
      biomarker detectability. An estimated near single molecule per particle
      efficiency of this method leads to sensitive detection of ovarian cancer
      biomarker CA125 in human blood plasma. This work opens new ways for earlier
      detection of cancers and for multiplex assay developments in various analytical
      applications from proteomics, genomics, and neurology fields. 

PMID- 25577362
TI  - Quantitative evaluation of bias in PCR amplification and next-generation
      sequencing derived from metabarcoding samples.
AB  - Unbiased identification of organisms by PCR reactions using universal primers
      followed by DNA sequencing assumes positive amplification. We used six universal
      loci spanning 48 plant species and quantified the bias at each step of the
      identification process from end point PCR to next-generation sequencing. End
      point amplification was significantly different for single loci and between
      species. Quantitative PCR revealed that Cq threshold for various loci, even
      within a single DNA extraction, showed 2,000-fold differences in DNA quantity
      after amplification. Next-generation sequencing (NGS) experiments in nine species
      showed significant biases towards species and specific loci using adaptor
      specific primers. NGS sequencing bias may be predicted to some extent by the Cq
      values of qPCR amplification. 

PMID- 25577363
TI  - High-throughput method for the determination of nitroimidazoles in muscle samples
      by liquid chromatography coupled to mass spectrometry.
AB  - We present a high-throughput confirmatory method for the analysis of 11
      nitroimidazoles in muscle samples (metronidazole, MNZ; dimetridazole, DMZ;
      ronidazole, RNZ; tinidazole, TNZ; carnidazole, CRZ; secnidazole semihydrate, SCZ;
      ornidazole, ORZ; metronidazole-hydroxy, MNZ-OH; ipronidazole, IPZ; ipronidazole
      hydroxy, IPZ-OH; and dimetridazole-hydroxy, HMMNI). Extraction with acetonitrile
      is efficient and simple, with the majority of recoveries ranging between 65 and
      101%, and without the need for clean-up of the extracts. The chromatographic
      analysis is performed using UPLC-QqQ-MS in the MRM mode, with an electrospray
      source operated in positive mode. Total chromatographic analysis time is 12 min.
      This method has been fully validated in muscle according to Decision 657/2002/CE
      guidelines, and the CCalpha values obtained were in the range of 0.04-0.4 MUg.kg(
      1). The method is currently used for the analysis of muscle samples and has been
      tested in other matrices of animal origin, such as kidney, retina and egg, with
      excellent results.

PMID- 25577364
TI  - Electrochemical sensor for determination of tulathromycin built with molecularly
      imprinted polymer film.
AB  - A novel tulathromycin (TLTMC) electrochemical sensor based on molecularly
      imprinted polymer (MIP) membranes was constructed. p-Aminothiophenol (p-ATP) and
      TLTMC were assembled on the surface of gold nanoparticles (AuNPs) modified on the
      gold electrode (GE) by the formation of Au-S bonds and hydrogen-bonding
      interactions. Besides, polymer membranes were formed by electropolymerization in
      a polymer solution containing p-ATP, tetrachloroaurate(III) acid (HAuCl4),
      tetrabutylammonium perchlorate (TBAP), and a template molecule TLTMC. A novel
      molecular imprinted sensor (MIS) in this experiment was achieved after the
      removal of TLTMC. Cyclic voltammetry (CV) and differential pulse voltammetry
      (DPV) measurements were used to illustrate the process of electropolymerization
      and its optimal conditions. The electrode with MIP obtained the linear of
      response range, which was between 3.0 * 10(-12) mol L(-1) and 7.0 * 10(-9) mol L(
      1), and the limit of detection was 1.0 * 10(-12) mol L(-1). All the obtained
      results indicate that the MIS tends to be an effective electrochemical technique
      for the determination of TLTMC in real-time and in a complicated matrix. 

PMID- 25577365
TI  - Raman spectroscopic investigation of 13CO 2 labeling and leaf dark respiration of
      Fagus sylvatica L. (European beech).
AB  - An important issue, in times of climate change and more extreme weather events,
      is the investigation of forest ecosystem reactions to these events. Longer
      drought periods stress the vitality of trees and promote mass insect outbreaks,
      which strongly affect ecosystem processes and services. Cavity-enhanced Raman gas
      spectrometry was applied for online multi-gas analysis of the gas exchange rates
      of O2 and CO2 and the labeling of Fagus sylvatica L. (European beech) seedlings
      with (13)CO2. The rapid monitoring of all these gases simultaneously allowed for
      the separation of photosynthetic uptake of CO2 by the beech seedlings and a
      constant (12)CO2 efflux via respiration and thus for a correction of the measured
      (12)CO2 concentrations in course of the labeling experiment. The effects of aphid
      infestation with the woolly beech aphid (Phyllaphis fagi L.) as well as the
      effect of a drought period on the respirational gas exchange were investigated. A
      slightly decreased respirational activity of drought-stressed seedlings in
      comparison to normally watered seedlings was found already for a low drought
      intensity. Cavity-enhanced Raman gas monitoring of O2, (12)CO2, and (13)CO2 was
      proven to be a powerful new tool for studying the effect of drought stress and
      aphid infestation on the respirational activity of European beech seedlings as an
      example of important forest species in Central Europe. 

PMID- 25577366
TI  - Preoperative planning and real-time assisted navigation by three-dimensional
      individual digital model in partial nephrectomy with three-dimensional
      laparoscopic system.
AB  - OBJECTIVE: To evaluate the feasibility and effectiveness of preoperative planning
      and real-time assisted surgical navigation for three-dimensional laparoscopic
      partial nephrectomy under the guidance of three-dimensional individual digital
      model (3D-IDM) created using three-dimensional medical image reconstructing and
      guiding system (3D-MIRGS). PATIENTS AND METHODS: Between May 2012 and February
      2014, 44 patients with cT1 renal tumors underwent retroperitoneal laparoscopic
      partial nephrectomy (LPN) using a three-dimensional laparoscopic system. The 3D
      IDMs were created using the 3D-MIRGS in 21 patients (3D-MIRGS group) between
      February 2013 and February 2014. After preoperative planning, operations were
      real-time assisted using composite 3D-IDMs, which were fused with two-dimensional
      retrolaparoscopic images. The remaining 23 patients underwent surgery without 3D
      MIRGS between May 2012 and February 2013; 14 of these patients were selected as a
      control group. Preoperative aspects and dimensions used for an anatomical score,
      "radius; exophytic/endophytic; nearness; anterior/posterior; location"
      nephrometry score, tumor size, operative time (OT), segmental renal artery
      clamping (SRAC) time, estimated blood loss (EBL), postoperative hospitalization,
      the preoperative serum creatinine level and ipsilateral glomerular filtration
      rate (GFR), as well as postoperative 6-month data were compared between groups.
      RESULTS: All the SRAC procedures were technically successful, and each targeted
      tumor was excised completely; final pathological margin results were negative.
      The OT was shorter (159.0 vs. 193.2 min; p < 0.001), and EBL (148.1 vs. 176.1 mL;
      p < 0.001) was reduced in the 3D-MIRGS group compared with controls. No
      statistically significant differences in SRAC time or postoperative
      hospitalization were found between the groups. Neither group showed any
      statistically significant increases in serum creatinine level or decreases in
      ipsilateral GFR postoperatively. CONCLUSIONS: Preoperative planning and real-time
      assisted surgical navigation using the 3D-IDM reconstructed from 3D-MIRGS and
      combined with the 3D laparoscopic system can facilitate LPN and result in precise
      SRAC and accurate excision of tumor that is both effective and safe.

PMID- 25577369
TI  - Free energy minimization to predict RNA secondary structures and computational
      RNA design.
AB  - Determining the RNA secondary structure from sequence data by computational
      predictions is a long-standing problem. Its solution has been approached in two
      distinctive ways. If a multiple sequence alignment of a collection of homologous
      sequences is available, the comparative method uses phylogeny to determine
      conserved base pairs that are more likely to form as a result of billions of
      years of evolution than by chance. In the case of single sequences, recursive
      algorithms that compute free energy structures by using empirically derived
      energy parameters have been developed. This latter approach of RNA folding
      prediction by energy minimization is widely used to predict RNA secondary
      structure from sequence. For a significant number of RNA molecules, the secondary
      structure of the RNA molecule is indicative of its function and its computational
      prediction by minimizing its free energy is important for its functional
      analysis. A general method for free energy minimization to predict RNA secondary
      structures is dynamic programming, although other optimization methods have been
      developed as well along with empirically derived energy parameters. In this
      chapter, we introduce and illustrate by examples the approach of free energy
      minimization to predict RNA secondary structures. 

PMID- 25577367
TI  - Hospital discharge survey on 4,199 peritonsillar abscesses in the Veneto region:
      what is the risk of recurrence and complications without tonsillectomy?
AB  - The Veneto region's database of hospital discharge records was queried for ICD-9
      codes corresponding to: peritonsillar abscess (PTA), PTA incision and drainage,
      tonsillectomy, pharyngeal-retropharyngeal abscess, cervical phlegmon, cervical
      abscess, and mediastinitis recorded from 1997 to 2006. All these codes were
      considered to identify cases of PTA recurrence and severe infectious
      complications occurring in conservatively treated patients. Among 4,199 patients
      whose PTA was incised and drained on admission to hospital, 1,532 were treated
      with tonsillectomy, while 2,667 were treated conservatively (without
      tonsillectomy). Abscess tonsillectomy was carried out almost exclusively in
      children (0-14 years of age), and only in 40 young and adult patients (0.95 %).
      The relapse rate after a single episode of PTA was 11.7 %, while potentially
      fatal complication occurred in 0.41 % of cases. Incidence of PTA hospital
      admission has remained stable in the considered period despite a 45 % reduction
      in the tonsillectomy rate. In conclusion, our data seem to show that conservative
      treatment for PTA is not associated with a significant risk of recurrence (and
      becomes minimal after 6-12 months), provided that patients have not suffered from
      previous PTA episodes.

PMID- 25577368
TI  - S100 alone has the same destructive effect on retinal ganglion cells as in
      combination with HSP 27 in an autoimmune glaucoma model.
AB  - As previously shown, immunization with ocular antigens, like heat shock protein
      27 (HSP 27), leads to retinal ganglion cell loss in an autoimmune glaucoma model.
      Aim of this study was to assess how immunization with S100 alone and in
      combination with HSP 27 affects retinal ganglion and macroglia cells. Rats were
      immunized with S100 or S100 plus HSP 27 (COMB). Neuronal cell density was
      evaluated on Nissl-stained flatmounts. Immunized groups showed a significant
      neuronal cell loss (S100, p = 0.005; COMB, p = 0.0005). A significant loss of
      retinal ganglion cells was also observed in both immunized groups on Brn-3a
      stained retinal cross-sections (S100, p = 0.003; COMB, p = 0.001). An increase in
      GFAP(+) area was noted in both groups (S100, p = 0.01; COMB, p = 0.001). In
      contrary, vimentin staining was not altered (S100/COMB, p > 0.05). In summary,
      immunization with solely S100 leads to retinal ganglion cell damage and reactive
      gliosis. While the combination of S100 plus HSP 27 also caused retinal ganglion
      cell loss and a glia response, the combination of the two antigens did not cause
      additional damage or more severe cell loss. We assume that both antigens might
      interact, possibly having inhibitory effects on each other and thus preventing
      additional damage to the retina.

PMID- 25577370
TI  - RNA secondary structure prediction from multi-aligned sequences.
AB  - It has been well accepted that the RNA secondary structures of most functional
      non-coding RNAs (ncRNAs) are closely related to their functions and are conserved
      during evolution. Hence, prediction of conserved secondary structures from
      evolutionarily related sequences is one important task in RNA bioinformatics; the
      methods are useful not only to further functional analyses of ncRNAs but also to
      improve the accuracy of secondary structure predictions and to find novel
      functional RNAs from the genome. In this review, I focus on common secondary
      structure prediction from a given aligned RNA sequence, in which one secondary
      structure whose length is equal to that of the input alignment is predicted. I
      systematically review and classify existing tools and algorithms for the problem,
      by utilizing the information employed in the tools and by adopting a unified
      viewpoint based on maximum expected gain (MEG) estimators. I believe that this
      classification will allow a deeper understanding of each tool and provide users
      with useful information for selecting tools for common secondary structure
      predictions. 

PMID- 25577371
TI  - A simple protocol for the inference of RNA global pairwise alignments.
AB  - RNA alignment is an important step in the annotation and characterization of
      unknown RNAs, and several methods have been developed to meet the need of fast
      and accurate alignments. Being the performances of the aligning methods affected
      by the input RNA features, finding the most suitable method is not trivial.
      Indeed, no available method clearly outperforms the others. Here we present a
      simple workflow to help choosing the more suitable method for RNA pairwise
      alignment. We tested the performances of six algorithms, based on different
      approaches, on datasets created by merging publicly available datasets of known
      or curated RNA secondary structure annotations with datasets of curated RNA
      alignments. Then, we simulated the frequent case where the secondary structure is
      unknown by using the same alignment datasets but ignoring the known structure and
      instead predicting it. In conclusion, the proposed workflow for pairwise RNA
      alignment depends on the input RNA primary sequence identity and the availability
      of reliable secondary structures. 

PMID- 25577373
TI  - Drawing and editing the secondary structure(s) of RNA.
AB  - Secondary structure diagrams are essential, in RNA biology, to communicate
      functional hypotheses and summarize structural data, and communicate them
      visually as drafts or finalized publication-ready figures. While many tools are
      currently available to automate the production of such diagrams, their capacities
      are usually partial, making it hard for a user to decide which to use in a given
      context. In this chapter, we guide the reader through the steps involved in the
      production of expressive publication-quality illustrations featuring the RNA
      secondary structure. We present major existing representations and layouts, and
      give precise instructions to produce them using available free software,
      including jViz.RNA, the PseudoViewer, RILogo, R-chie, RNAplot, R2R, and VARNA. We
      describe the file formats and structural descriptions accepted by popular RNA
      visualization tools. We also provide command lines and Python scripts to ease the
      user's access to advanced features. Finally, we discuss and illustrate
      alternative approaches to visualize the secondary structure in the presence of
      probing data, pseudoknots, RNA-RNA interactions, and comparative data. 

PMID- 25577372
TI  - De novo secondary structure motif discovery using RNAProfile.
AB  - RNA secondary structure plays critical roles in several biological processes. For
      example, many trans-acting noncoding RNA genes and cis-acting RNA regulatory
      elements present functional motifs, conserved both in structure and sequence,
      that can be hardly detected by primary sequence analysis alone. We describe here
      how conserved secondary structure motifs shared by functionally related RNA
      sequences can be detected through the software tool RNAProfile. RNAProfile takes
      as input a set of unaligned RNA sequences expected to share a common motif, and
      outputs the regions that are most conserved throughout the sequences, according
      to a similarity measure that takes into account both the sequence of the regions
      and the secondary structure they can form according to base-pairing and
      thermodynamic rules. The method is split into two parts. First, it identifies
      candidate regions within the input sequences, and associates with each region a
      locally optimal secondary structure. Then, it compares candidate regions to one
      another, both at sequence and structure level, and builds motifs exploring the
      search space through a greedy heuristic. We provide a detailed guide to the
      different parameters that can be employed, and usage examples showing the
      different software capabilities.

PMID- 25577374
TI  - Modeling and predicting RNA three-dimensional structures.
AB  - Modeling the three-dimensional structure of RNAs is a milestone toward better
      understanding and prediction of nucleic acids molecular functions. Physics-based
      approaches and molecular dynamics simulations are not tractable on large
      molecules with all-atom models. To address this issue, coarse-grained models of
      RNA three-dimensional structures have been developed. In this chapter, we
      describe a graphical modeling based on the Leontis-Westhof extended base-pair
      classification. This representation of RNA structures enables us to identify
      highly conserved structural motifs with complex nucleotide interactions in
      structure databases. Further, we show how to take advantage of this knowledge to
      quickly and simply predict three-dimensional structures of large RNA molecules. 

PMID- 25577375
TI  - Fast prediction of RNA-RNA interaction using heuristic algorithm.
AB  - Interaction between two RNA molecules plays a crucial role in many medical and
      biological processes such as gene expression regulation. In this process, an RNA
      molecule prohibits the translation of another RNA molecule by establishing stable
      interactions with it. Some algorithms have been formed to predict the structure
      of the RNA-RNA interaction. High computational time is a common challenge in most
      of the presented algorithms. In this context, a heuristic method is introduced to
      accurately predict the interaction between two RNAs based on minimum free energy
      (MFE). This algorithm uses a few dot matrices for finding the secondary structure
      of each RNA and binding sites between two RNAs. Furthermore, a parallel version
      of this method is presented. We describe the algorithm's concurrency and
      parallelism for a multicore chip. The proposed algorithm has been performed on
      some datasets including CopA-CopT, R1inv-R2inv, Tar-Tar*, DIS-DIS, and IncRNA54
      RepZ in Escherichia coli bacteria. The method has high validity and efficiency,
      and it is run in low computational time in comparison to other approaches. 

PMID- 25577376
TI  - Quality control of RNA-seq experiments.
AB  - Direct sequencing of the complementary DNA (cDNA) using high-throughput
      sequencing technologies (RNA-seq) is widely used and allows for more
      comprehensive understanding of the transcriptome than microarray. In theory, RNA
      seq should be able to precisely identify and quantify all RNA species, small or
      large, at low or high abundance. However, RNA-seq is a complicated, multistep
      process involving reverse transcription, amplification, fragmentation,
      purification, adaptor ligation, and sequencing. Improper operations at any of
      these steps could make biased or even unusable data. Additionally, RNA-seq
      intrinsic biases (such as GC bias and nucleotide composition bias) and
      transcriptome complexity can also make data imperfect. Therefore, comprehensive
      quality assessment is the first and most critical step for all downstream
      analyses and results interpretation. This chapter discusses the most widely used
      quality control metrics including sequence quality, sequencing depth, reads
      duplication rates (clonal reads), alignment quality, nucleotide composition bias,
      PCR bias, GC bias, rRNA and mitochondria contamination, coverage uniformity, etc.

PMID- 25577377
TI  - Accurate mapping of RNA-Seq data.
AB  - The mapping of RNA-Seq data on genome is not the same as DNA-Seq data, because
      the junction reads span two exons and have no identical matches at reference
      genome. In this chapter, we describe a junction read aligner SpliceMap that is
      based on an algorithm of "half-read seeding" and "seeding extension." Four
      analysis steps are integrated in SpliceMap (half-read mapping, seeding selection,
      seeding extension and junction search, and paired-end filtering), and all toning
      parameters of these steps can be editable in a single configuration file. Thus,
      SpliceMap can be executed by a single command. While we describe the analysis
      steps of SpliceMap, we illustrate how to choose the parameters according to the
      research interest and RNA-Seq data quality by an example of human brain RNA-Seq
      data. 

PMID- 25577378
TI  - Quantifying entire transcriptomes by aligned RNA-seq data.
AB  - Massive Parallel Sequencing methods (MPS) can extend and improve the knowledge
      obtained by conventional microarray technology, both for mRNAs and noncoding
      RNAs. Although RNA quality and library preparation protocols are the main source
      of variability, the bioinformatics pipelines for RNA-seq data analysis are very
      complex and the choice of different tools at each stage of the analysis can
      significantly affect the overall results. In this chapter we describe the
      pipelines we use to detect miRNA and mRNA differential expression. 

PMID- 25577379
TI  - Transcriptome assembly and alternative splicing analysis.
AB  - Alternative Splicing (AS) is the molecular phenomenon whereby multiple
      transcripts are produced from the same gene locus. As a consequence, it is
      responsible for the expansion of eukaryotic transcriptomes. Aberrant AS is
      involved in the onset and progression of several human diseases. Therefore, the
      characterization of exon-intron structure of a gene and the detection of
      corresponding transcript isoforms is an extremely relevant biological task.
      Nonetheless, the computational prediction of AS events and the repertoire of
      alternative transcripts is yet a challenging issue. Hereafter we introduce
      PIntron, a software package to predict the exon-intron structure and the full
      length isoforms of a gene given a genomic region and a set of transcripts (ESTs
      and/or mRNAs). The software is open source and available at
      http://pintron.algolab.eu. PIntron has been designed for (and extensively tested
      on) a standard workstation without requiring dedicated expensive hardware. It
      easily manages large genomic regions and more than 20,000 ESTs, achieving good
      accuracy as shown in an experimental evaluation performed on 112 well-annotated
      genes selected from the ENCODE human regions used as training set in the EGASP
      competition.

PMID- 25577380
TI  - Detection of post-transcriptional RNA editing events.
AB  - The advent of deep sequencing technologies has greatly improved the study of
      complex eukaryotic genomes and transcriptomes, providing the unique opportunity
      to investigate posttranscriptional molecular mechanisms as alternative splicing
      and RNA editing at single base-pair resolution. RNA editing by adenosine
      deamination (A-to-I) is widespread in humans and can lead to a variety of
      biological effects depending on the RNA type or the RNA region involved in the
      editing modification. Hereafter, we describe an easy and reproducible
      computational protocol for the identification of candidate RNA editing sites in
      human using deep transcriptome (RNA-Seq) and genome (DNA-Seq) sequencing data.

PMID- 25577381
TI  - Prediction of miRNA targets.
AB  - Computational methods for miRNA target prediction are currently undergoing
      extensive review and evaluation. There is still a great need for improvement of
      these tools and bioinformatics approaches are looking towards high-throughput
      experiments in order to validate predictions. The combination of large-scale
      techniques with computational tools will not only provide greater credence to
      computational predictions but also lead to the better understanding of specific
      biological questions. Current miRNA target prediction tools utilize probabilistic
      learning algorithms, machine learning methods and even empirical biologically
      defined rules in order to build models based on experimentally verified miRNA
      targets. Large-scale protein downregulation assays and next-generation sequencing
      (NGS) are now being used to validate methodologies and compare the performance of
      existing tools. Tools that exhibit greater correlation between computational
      predictions and protein downregulation or RNA downregulation are considered the
      state of the art. Moreover, efficiency in prediction of miRNA targets that are
      concurrently verified experimentally provides additional validity to
      computational predictions and further highlights the competitive advantage of
      specific tools and their efficacy in extracting biologically significant results.
      In this review paper, we discuss the computational methods for miRNA target
      prediction and provide a detailed comparison of methodologies and features
      utilized by each specific tool. Moreover, we provide an overview of current state
      of-the-art high-throughput methods used in miRNA target prediction. 

PMID- 25577383
TI  - NGS-Trex: an automatic analysis workflow for RNA-Seq data.
AB  - RNA-Seq technology allows the rapid analysis of whole transcriptomes taking
      advantage of next-generation sequencing platforms. Moreover with the constant
      decrease of the cost of NGS analysis RNA-Seq is becoming very popular and
      widespread. Unfortunately data analysis is quite demanding in terms of
      bioinformatic skills and infrastructures required, thus limiting the potential
      users of this method. Here we describe the complete analysis of sample data from
      raw sequences to data mining of results by using NGS-Trex platform, a low user
      interaction, fully automatic analysis workflow. Used through a web interface, NGS
      Trex processes data and profiles the transcriptome of the samples identifying
      expressed genes, transcripts, and new and known splice variants. It also detects
      differentially expressed genes and transcripts across different experiments.

PMID- 25577382
TI  - Using deep sequencing data for identification of editing sites in mature miRNAs.
AB  - Deep sequencing has many possible applications; one of them is the identification
      and quantification of RNA editing sites. The most common type of RNA editing is
      adenosine to inosine (A-to-I) editing. A prerequisite for this editing process is
      a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the
      microRNA (miRNA) maturation process, and it is therefore expected that miRNAs are
      affected by A-to-I editing. Indeed, tens of editing sites were found in miRNAs,
      some of which change the miRNA binding specificity. Here, we describe a protocol
      for the identification of RNA editing sites in mature miRNAs using deep
      sequencing data. 

PMID- 25577384
TI  - e-DNA meta-barcoding: from NGS raw data to taxonomic profiling.
AB  - In recent years, thanks to the essential support provided by the Next-Generation
      Sequencing (NGS) technologies, Metagenomics is enabling the direct access to the
      taxonomic and functional composition of mixed microbial communities living in any
      environmental niche, without the prerequisite to isolate or culture the single
      organisms. This approach has already been successfully applied for the analysis
      of many habitats, such as water or soil natural environments, also characterized
      by extreme physical and chemical conditions, food supply chains, and animal
      organisms, including humans. A shotgun sequencing approach can lead to
      investigate both organisms and genes diversity. Anyway, if the purpose is limited
      to explore the taxonomic complexity, an amplicon-based approach, based on PCR
      targeted sequencing of selected genetic species markers, commonly named "meta
      barcodes", is desirable. Among the genomic regions most widely used for the
      discrimination of bacterial organisms, in some cases up to the species level,
      some hypervariable domains of the gene coding for the 16S rRNA occupy a prominent
      place. The amplification of a certain meta-barcode from a microbial community
      through the use of PCR primers able to work in the entire considered taxonomic
      group is the first task after the extraction of the total DNA. Generally, this
      step is followed by the high-throughput sequencing of the resulting amplicons
      libraries by means of a selected NGS platform. Finally, the interpretation of the
      huge amount of produced data requires appropriate bioinformatics tools and know
      how in addition to efficient computational resources. Here a computational
      methodology suitable for the taxonomic characterization of 454 meta-barcode
      sequences is described in detail. In particular, a dataset covering the V1-V3
      region belonging to the bacterial 16S rRNA coding gene and produced in the Human
      Microbiome Project (HMP) from a palatine tonsils sample is analyzed. The proposed
      exercise includes the basic steps to manage raw sequencing data, remove
      amplification and pyrosequencing errors, and finally map sequences on the
      taxonomy.

PMID- 25577385
TI  - Deciphering metatranscriptomic data.
AB  - Metatranscriptomic data contributes another piece of the puzzle to understanding
      the phylogenetic structure and function of a community of organisms. High-quality
      total RNA is a bountiful mixture of ribosomal, transfer, messenger and other
      noncoding RNAs, where each family of RNA is vital to answering questions
      concerning the hidden microbial world. Software tools designed for deciphering
      metatranscriptomic data fall under two main categories: the first is to
      reassemble millions of short nucleotide fragments produced by high-throughput
      sequencing technologies into the original full-length transcriptomes for all
      organisms within a sample, and the second is to taxonomically classify the
      organisms and determine their individual functional roles within a community.
      Species identification is mainly established using the ribosomal RNA genes,
      whereas the behavior and functionality of a community is revealed by the
      messenger RNA of the expressed genes. Numerous chemical and computational methods
      exist to separate families of RNA prior to conducting further downstream
      analyses, primarily suitable for isolating mRNA or rRNA from a total RNA sample.
      In this chapter, we demonstrate a computational technique for filtering rRNA from
      total RNA using the software SortMeRNA. Additionally, we propose a post
      processing pipeline using the latest software tools to conduct further studies on
      the filtered data, including the reconstruction of mRNA transcripts for
      functional analyses and phylogenetic classification of a community using the
      ribosomal RNA. 

PMID- 25577386
TI  - RIP-Seq data analysis to determine RNA-protein associations.
AB  - Next-generation sequencing (NGS) technologies have opened new avenues of
      unprecedented power for research in molecular biology and genetics. In
      particular, their application to the study of RNA-binding proteins (RBPs),
      extracted through immunoprecipitation (RIP), permits to sequence and characterize
      all RNAs that were found to be bound in vivo by a given RBP (RIP-Seq). On the
      other hand, NGS-based experiments, including RIP-Seq, produce millions of short
      sequence fragments that have to be processed with suitable bioinformatic tools
      and methods to recover and/or quantify the original sequence sample. In this
      chapter we provide a survey of different approaches that can be taken for the
      analysis of RIP-Seq data and the identification of the RNAs bound by a given RBP.

PMID- 25577387
TI  - The ViennaRNA web services.
AB  - The ViennaRNA package is a widely used collection of programs for thermodynamic
      RNA secondary structure prediction. Over the years, many additional tools have
      been developed building on the core programs of the package to also address
      issues related to noncoding RNA detection, RNA folding kinetics, or efficient
      sequence design considering RNA-RNA hybridizations. The ViennaRNA web services
      provide easy and user-friendly web access to these tools. This chapter describes
      how to use this online platform to perform tasks such as prediction of minimum
      free energy structures, prediction of RNA-RNA hybrids, or noncoding RNA
      detection. The ViennaRNA web services can be used free of charge and can be
      accessed via http://rna.tbi.univie.ac.at.

PMID- 25577388
TI  - Exploring the RNA editing potential of RNA-Seq data by ExpEdit.
AB  - Revealing the impact of A-to-I RNA editing in RNA-Seq experiments is relevant in
      humans because RNA editing can influence gene expression. In addition, its
      deregulation has been linked to a variety of human diseases. Exploiting the RNA
      editing potential in complete RNA-Seq datasets, however, is a challenging task.
      Indeed, no dedicated software is available, and sometimes deep computational
      skills and appropriate hardware resources are required. To explore the impact of
      known RNA editing events in massive transcriptome sequencing experiments, we
      developed the ExpEdit web service application. In the present work, we provide an
      overview of ExpEdit as well as methodologies to investigate known RNA editing in
      human RNA-Seq datasets. 

PMID- 25577389
TI  - A guideline for the annotation of UTR regulatory elements in the UTRsite
      collection.
AB  - Gene expression regulatory elements are scattered in gene promoters and pre
      mRNAs. In particular, RNA elements lying in untranslated regions (5' and 3'UTRs)
      are poorly studied because of their peculiar features (i.e., a combination of
      primary and secondary structure elements) which also pose remarkable
      computational challenges. Several years ago, we began collecting experimentally
      characterized UTR regulatory elements, developing the specialized database
      UTRsite. This paper describes the detailed guidelines to annotate cis-regulatory
      elements in 5' and 3' UnTranslated Regions (UTRs) by computational analyses,
      retracing all main steps used by UTRsite curators. 

PMID- 25577390
TI  - Rfam: annotating families of non-coding RNA sequences.
AB  - The primary task of the Rfam database is to collate experimentally validated
      noncoding RNA (ncRNA) sequences from the published literature and facilitate the
      prediction and annotation of new homologues in novel nucleotide sequences. We
      group homologous ncRNA sequences into "families" and related families are further
      grouped into "clans." We collate and manually curate data cross-references for
      these families from other databases and external resources. Our Web site offers
      researchers a simple interface to Rfam and provides tools with which to annotate
      their own sequences using our covariance models (CMs), through our tools for
      searching, browsing, and downloading information on Rfam families. In this
      chapter, we will work through examples of annotating a query sequence, collating
      family information, and searching for data. 

PMID- 25577391
TI  - ASPicDB: a database web tool for alternative splicing analysis.
AB  - Alternative splicing (AS) is a basic molecular phenomenon that increases the
      functional complexity of higher eukaryotic transcriptomes. Indeed, through AS
      individual gene loci can generate multiple RNAs from the same pre-mRNA. AS has
      been investigated in a variety of clinical and pathological studies, such as the
      transcriptome regulation in cancer. In human, recent works based on massive RNA
      sequencing indicate that >95 % of pre-mRNAs are processed to yield multiple
      transcripts. Given the biological relevance of AS, several computational efforts
      have been done leading to the implementation of novel algorithms and specific
      specialized databases. Here we describe the web application ASPicDB that allows
      the recovery of detailed biological information about the splicing mechanism.
      ASPicDB provides powerful querying systems to interrogate AS events at gene,
      transcript, and protein levels. Finally, ASPicDB includes web visualization
      instruments to browse and export results for further off-line analyses. 

PMID- 25577392
TI  - Analysis of alternative splicing events in custom gene datasets by AStalavista.
AB  - Alternative splicing (AS) is a eukaryotic principle to derive more than one RNA
      product from transcribed genes by removing distinct subsets of introns from a
      premature polymer. We know today that this process is highly regulated and makes
      up a large part of the differences between species, cell types, and states. The
      key to compare AS across different genes or organisms is to tokenize the AS
      phenomenon into atomary units, so-called AS events. These events then usually are
      grouped by common patterns to investigate the underlying molecular mechanisms
      that drive their regulation. However, attempts to decompose loci with AS
      observations into events are often hampered by applying a limited set of a priori
      defined event patterns which are not capable to describe all AS configurations
      and therefore cannot decompose the phenomenon exhaustively. In this chapter, we
      describe working scenarios of AStalavista, a computational method that reports
      all AS events reflected by transcript annotations. We show how to practically
      employ AStalavista to study AS variation in complex transcriptomes, as
      characterized by the human GENCODE annotation. Our examples demonstrate how the
      inherent and universal AStalavista paradigm allows for an automatic delineation
      of AS events in custom gene datasets. Additionally, we sketch an example of an
      AStalavista use case including next-generation sequencing data (RNA-Seq) to
      enrich the landscape of discovered AS events.

PMID- 25577393
TI  - Computational design of artificial RNA molecules for gene regulation.
AB  - RNA interference (RNAi) is a powerful tool for the regulation of gene expression.
      Small exogenous noncoding RNAs (ncRNAs) such as siRNA and shRNA are the active
      silencing agents, intended to target and cleave complementary mRNAs in a specific
      way. They are widely and successfully employed in functional studies, and several
      ongoing and already completed siRNA-based clinical trials suggest encouraging
      results in the regulation of overexpressed genes in disease. siRNAs share many
      aspects of their biogenesis and function with miRNAs, small ncRNA molecules
      transcribed from endogenous genes which are able to repress the expression of
      target mRNAs by either inhibiting their translation or promoting their
      degradation. Although siRNA and artificial miRNA molecules can significantly
      reduce the expression of overexpressed target genes, cancer and other diseases
      can also be triggered or sustained by upregulated miRNAs. Thus, in the past
      recent years, molecular tools for miRNA silencing, such as antagomiRs and miRNA
      sponges, have been developed. These molecules have shown their efficacy in the
      derepression of genes downregulated by overexpressed miRNAs. In particular, while
      a single antagomiR is able to inhibit a single complementary miRNA, an artificial
      sponge construct usually contains one or more binding sites for one or more
      miRNAs and functions by competing with the natural targets of these miRNAs. As a
      consequence, natural miRNA targets are reexpressed at their physiological level.
      In this chapter we review the most successful methods for the computational
      design of siRNAs, antagomiRs, and miRNA sponges and describe the most popular
      tools that implement them.

PMID- 25577394
TI  - Rhodopsin gene polymorphism associated with divergent light environments in
      Atlantic cod.
AB  - The spectral sensitivity of visual pigments in vertebrate eyes is optimized for
      specific light conditions. One of such pigments, rhodopsin (RH1), mediates dim
      light vision. Amino acid replacements at tuning sites may alter spectral
      sensitivity, providing a mechanism to adapt to ambient light conditions and depth
      of habitat in fish. Here we present a first investigation of RH1 gene
      polymorphism among two ecotypes of Atlantic cod in Icelandic waters, which
      experience divergent light environments throughout the year due to alternative
      foraging behaviour. We identified one synonymous single nucleotide polymorphism
      (SNP) in the RH1 protein coding region and one in the 3' untranslated region (3'
      UTR) that are strongly divergent between these two ecotypes. Moreover, these
      polymorphisms coincided with the well-known panthophysin (Pan I) polymorphism
      that differentiates coastal and frontal (migratory) populations of Atlantic cod.
      While the RH1 SNPs do not provide direct inference for a specific molecular
      mechanism, their association with this dim-sensitive pigment indicates the
      involvement of the visual system in local adaptation of Atlantic cod. 

PMID- 25577395
TI  - Isoprenoid drugs, biofuels, and chemicals--artemisinin, farnesene, and beyond.
AB  - Isoprenoids have been identified and used as natural pharmaceuticals, fragrances,
      solvents, and, more recently, advanced biofuels. Although isoprenoids are most
      commonly found in plants, researchers have successfully engineered both the
      eukaryotic and prokaryotic isoprenoid biosynthetic pathways to produce these
      valuable chemicals in microorganisms at high yields. The microbial synthesis of
      the precursor to artemisinin--an important antimalarial drug produced from the
      sweet wormwood Artemisia annua--serves as perhaps the most successful example of
      this approach. Through advances in synthetic biology and metabolic engineering,
      microbial-derived semisynthetic artemisinin may soon replace plant-derived
      artemisinin as the primary source of this valuable pharmaceutical. The richness
      and diversity of isoprenoid structures also make them ideal candidates for
      advanced biofuels that may act as "drop-in" replacements for gasoline, diesel,
      and jet fuel. Indeed, the sesquiterpenes farnesene and bisabolene, monoterpenes
      pinene and limonene, and hemiterpenes isopentenol and isopentanol have been
      evaluated as fuels or fuel precursors. As in the artemisinin project, these
      isoprenoids have been produced microbially through synthetic biology and
      metabolic engineering efforts. Here, we provide a brief review of the numerous
      isoprenoid compounds that have found use as pharmaceuticals, flavors, commodity
      chemicals, and, most importantly, advanced biofuels. In each case, we highlight
      the metabolic engineering strategies that were used to produce these compounds
      successfully in microbial hosts. In addition, we present a current outlook on
      microbial isoprenoid production, with an eye towards the many challenges that
      must be addressed to achieve higher yields and industrial-scale production.

PMID- 25577396
TI  - Construction of Escherichia Coli Cell Factories for Production of Organic Acids
      and Alcohols.
AB  - Production of bulk chemicals from renewable biomass has been proved to be
      sustainable and environmentally friendly. Escherichia coli is the most commonly
      used host strain for constructing cell factories for production of bulk chemicals
      since it has clear physiological and genetic characteristics, grows fast in
      minimal salts medium, uses a wide range of substrates, and can be genetically
      modified easily. With the development of metabolic engineering, systems biology,
      and synthetic biology, a technology platform has been established to construct E.
      coli cell factories for bulk chemicals production. In this chapter, we will
      introduce this technology platform, as well as E. coli cell factories
      successfully constructed for production of organic acids and alcohols.

PMID- 25577397
TI  - Access to medication and pharmacy services for resettled refugees: a systematic
      review.
AB  - The difficulties that resettled refugees experience in accessing primary health
      care services have been widely documented. In most developed countries,
      pharmacists are often the first health-care professional contacted by consumers;
      however, the ability of refugees to access community pharmacies and medication
      may be limited. This review systematically reviewed the literature and
      synthesised findings of research that explored barriers and/or facilitators of
      access to medication and pharmacy services for resettled refugees. This review
      adhered to guidelines for systematic reviews by PRISMA (preferred reporting items
      for systematic reviews and meta-analyses). Databases were searched during March
      2014 and included Scopus, ProQuest Sociological Abstracts, PubMed, Embase and
      APAIS Health. The Australian and International grey literature was also explored.
      Nine studies met the quality and inclusion criteria. The research reported in
      seven of the nine studies was conducted in the US, one was conducted in Australia
      and the other in the UK. The majority of studies focussed on South-east Asian
      refugees. Themes identified across the studies included language and the use of
      interpreters; navigating the Western health-care system; culture and illness
      beliefs; medication non-adherence; use of traditional medicine; and family, peer
      and community support. There is a significant paucity of published research
      exploring barriers to medication and pharmacy services among resettled refugees.
      This systematic review highlights the need for appropriate interpreting and
      translation services, as well as pharmacy staff demonstrating effective cross
      cultural communication skills.

PMID- 25577398
TI  - Unravelling adverse reactions to NSAIDs using systems biology.
AB  - We introduce the reader to systems biology, using adverse drug reactions (ADRs),
      specifically hypersensitivity reactions to multiple non-steroidal anti
      inflammatory drugs (NSAIDs), as a model. To disentangle the different processes
      that contribute to these reactions - from drug intake to the appearance of
      symptoms - it will be necessary to create high-throughput datasets. Just as
      crucial will be the use of systems biology to integrate and make sense of them.
      We review previous work using systems biology to study related pathologies such
      as asthma/allergy, and NSAID metabolism. We show examples of their application to
      NSAIDs-hypersensitivity using current datasets. We describe breakthroughs in high
      throughput technology and speculate on their use to improve our understanding of
      this and other drug-induced pathologies. 

PMID- 25577399
TI  - Finding the optimal combination therapy for the treatment of newly diagnosed AML
      in older patients unfit for intensive therapy.
AB  - There is no standard of care for older patients with newly diagnosed acute
      myeloid leukemia (AML) unfit for intensive therapy, and prognosis with currently
      recommended low-intensity therapies (decitabine, azacitidine, and low-dose
      cytarabine [LDAC]) remains poor. One promising strategy is to combine low
      intensity treatments with novel agents. Gemtuzumab ozogamicin, tipifarnib, and
      barasertib have been investigated in phase 2/3 or 3 trials combined with LDAC,
      and phase 3 trials are currently investigating sapacitabine plus decitabine, and
      volasertib plus LDAC in AML. This review discusses current treatment
      recommendations and the development of combination therapies for older patients
      unfit for intensive therapy.

PMID- 25577400
TI  - Evaluation of RANO response criteria compared to clinician evaluation in WHO
      grade III anaplastic astrocytoma: implications for clinical trial reporting and
      patterns of failure.
AB  - The utility of current response criteria has not been established in anaplastic
      astrocytoma (AA). We retrospectively reviewed MR images for 20 patients with AA
      and compared RANO-based approaches to clinician impression described as follow:
      (1) standard RANO-based criteria met by growth of or development of new enhancing
      lesion (RANO-C), (2) RANO criteria for progression based on significant FLAIR
      increase (RANO-F) and (3) clinical progression usually resulting in change of
      treatment (Clinical). Patterns of failure (POF) were analyzed utilizing all
      proposed progression MRIs fused with the patients' radiotherapy treatment plan.
      With an overall median survival of 24.3 months, development of new enhancing
      lesion was the most common determinant of progression (70 % of patients). Median
      time to RANO-C, RANO-F and Clinical progression was 9.2, 9.2 and 11.76 months
      respectively. RANO-C and RANO-F preceded Clinical in 70 and 55 % of patients,
      respectively. In six patients (30 %) Clinical was concurrent with RANO-F; four of
      six also met RANO-C. POF for FLAIR component differed based on time point used to
      determine progression. FLAIR POF was more often marginal or distant when
      progression was defined clinically compared to either RANO-C or RANO-F criteria.
      Central POF based on FLAIR at Clinical determination of progression was
      associated with significantly poorer OS (9.8 vs. 34.4 months). Clinical
      progression occurs later than progression determined by RANO-based criteria.
      Evaluation of POF based on FLAIR signal abnormality at the time of clinical
      progression suggests central recurrences are associated with worse survival.

PMID- 25577401
TI  - Current challenges in designing GBM trials for immunotherapy.
AB  - Immune system modulation is evolving into a promising treatment modality in
      glioblastoma. Our growing understanding of glioma immunobiology has fueled
      efforts to develop immunotherapeutic strategies to combat this lethal primary
      brain tumor. Autologous stimulated lymphocytes, immunotherapy with cytokines and
      dendritic cells, immune checkpoint inhibitors, virotherapy, and tumor or peptide
      based vaccines are immunotherapy approaches under active investigation. A number
      of challenges are evident in the design of immunotherapy clinical trials in
      glioblastoma including patient selection, immune and imaging response monitoring,
      and evaluation of clinical outcome. 

PMID- 25577402
TI  - Optically driven oscillations of ellipsoidal particles. Part I: experimental
      observations.
AB  - We report experimental observations of the mechanical effects of light on
      ellipsoidal micrometre-sized dielectric particles, in water as the continuous
      medium. The particles, made of polystyrene, have shapes varying between near disk
      like (aspect ratio k = 0.2) to very elongated needle-like (k = 8). Rather than
      the very tightly focused beam geometry of optical tweezers, we use a moderately
      focused laser beam to manipulate particles individually by optical levitation.
      The geometry allows us varying the longitudinal position of the particle, and to
      capture images perpendicular to the beam axis. Experiments show that moderate-k
      particles are radially trapped with their long axis lying parallel to the beam.
      Conversely, elongated (k > 3) or flattened (k < 0.3) ellipsoids never come to
      rest, and permanently "dance" around the beam, through coupled translation
      rotation motions. The oscillations are shown to occur in general, be the particle
      in bulk water or close to a solid boundary, and may be periodic or irregular. We
      provide evidence for two bifurcations between static and oscillating states, at k
      ~ 0.33 and k ~ 3 for oblate and prolate ellipsoids, respectively. Based on a
      recently developed 2-dimensional ray-optics simulation (Mihiretie et al., EPL
      100, 48005 (2012)), we propose a simple model that allows understanding the
      physical origin of the oscillations.

PMID- 25577403
TI  - Optically driven oscillations of ellipsoidal particles. Part II: ray-optics
      calculations.
AB  - We report numerical calculations on the mechanical effects of light on micrometer
      sized dielectric ellipsoids immersed in water. We used a simple two-dimensional
      ray-optics model to compute the radiation pressure forces and torques exerted on
      the object as a function of position and orientation within the laser beam.
      Integration of the equations of motion, written in the Stokes limit, yields the
      particle dynamics that we investigated for different aspect ratios k. Whether the
      beam is collimated or focused, the results show that above a critical aspect
      ratio k(C), the ellipsoids cannot be stably trapped on the beam axis; the
      particle never comes to rest and rather oscillates permanently in a back-and
      forth motion involving both translation and rotation in the vicinity of the beam.
      Such oscillations are a direct evidence of the non-conservative character of
      optical forces. Conversely, stable trapping can be achieved for k < k(C) with the
      particle standing idle in a vertical position. These predictions are in very good
      qualitative agreement with experimental observations. The physical origin of the
      instability may be understood from the force and torque fields whose structures
      greatly depend on the ellipsoid aspect ratio and beam diameter. The oscillations
      arise from a non-linear coupling of the forces and torques and the torque
      amplitude was identified as the bifurcation control parameter. Interestingly,
      simulations predict that sustained oscillations can be suppressed through the use
      of two coaxial counterpropagating beams, which may be of interest whenever a
      static equilibrium is required as in basic force and torque measurements or
      technological applications.

PMID- 25577404
TI  - The predictive value of obstructive sleep apnoea severity on clinical outcomes
      following maxillomandibular advancement surgery.
AB  - We aimed to evaluate whether the severity of preoperative obstructive sleep
      apnoea (OSA) has potential predictive value for the clinician assessing patients
      referred for maxillomandibular advancment surgery. We performed a retrospective
      analysis of consecutive patients who underwent maxillofacial operations for OSA
      at our institution. We stratified them into 2 groups according to
      apnoea/hypopnoea index (AHI) scores calculated from a preoperative sleep study:
      mild-moderate OSA (AHI less than 30) and severe OSA (AHI 30 and above). Both
      groups were matched for baseline demographic and clinical characteristics. We
      compared postoperative scores for the AHI and Epworth sleepiness scale (ESS), and
      lowest recorded oxygen saturation between groups. We identified 51 patients of
      whom 39 had complete data available for inclusion in our analysis. We found no
      statistically significant difference in the postoperative AHI scores between the
      two groups. The reduction in the mean ESS after operation was greater in the
      severe group than in the mild-moderate group (mean (SD) ESS 4 (3) compared with 9
      (6), p<0.05). There were high rates of surgical success (postoperative AHI less
      than 15) in both groups, and results were comparable (mild-moderate group 82%,
      severe group 86%). The preoperative AHI does not appear to be a good predictor of
      surgical success after maxillomandibular advancement surgery. Patients with
      severe OSA postoperatively demonstrated a greater improvement in their subjective
      symptoms, when compared to subjects with mild-moderate OSA.

PMID- 25577405
TI  - Data-driven CT protocol review and management-experience from a large academic
      hospital.
AB  - PURPOSE: Protocol review plays a critical role in CT quality assurance, but large
      numbers of protocols and inconsistent protocol names on scanners and in exam
      records make thorough protocol review formidable. In this investigation, we
      report on a data-driven cataloging process that can be used to assist in the
      reviewing and management of CT protocols. METHODS: We collected lists of scanner
      protocols, as well as 18 months of recent exam records, for 10 clinical scanners.
      We developed computer algorithms to automatically deconstruct the protocol names
      on the scanner and in the exam records into core names and descriptive
      components. Based on the core names, we were able to group the scanner protocols
      into a much smaller set of "core protocols," and to easily link exam records with
      the scanner protocols. We calculated the percentage of usage for each core
      protocol, from which the most heavily used protocols were identified. RESULTS:
      From the percentage-of-usage data, we found that, on average, 18, 33, and 49 core
      protocols per scanner covered 80%, 90%, and 95%, respectively, of all exams.
      These numbers are one order of magnitude smaller than the typical numbers of
      protocols that are loaded on a scanner (200-300, as reported in the literature).
      Duplicated, outdated, and rarely used protocols on the scanners were easily
      pinpointed in the cataloging process. CONCLUSIONS: The data-driven cataloging
      process can facilitate the task of protocol review.

PMID- 25577406
TI  - The impaired radiologist.
AB  - Radiologists are faced with ever-increasing challenges in the needs of the
      practice, in both private and academic settings. Targeted information about
      protecting and maintaining the physical, mental, and emotional health of the
      radiologist is highly limited. Impairment is a functional classification that
      implies that the individual affected by a disease is unable to perform specific
      activities. Radiologists can suffer from the same illnesses as any human being,
      which include substance abuse and addiction, as well as chronic infectious
      diseases such as human immunodeficiency virus, hepatitis B and C, and
      tuberculosis. This article is intended to educate radiologists and leaders about
      various forms of physician impairment. It provides discussion of the challenges
      related to such impairment and provides tools and resources to address the
      impaired radiologist. 

PMID- 25577407
TI  - Use of high-frequency visual stimuli above the critical flicker frequency in a
      SSVEP-based BMI.
AB  - OBJECTIVE: This study presents a new steady-state visual evoked potential (SSVEP)
      based brain-machine interface (BMI) using flickering visual stimuli at
      frequencies greater than the critical flicker frequency (CFF). METHODS: We first
      asked participants to fixate on a green/blue flicker (30-70Hz), and SSVEP
      amplitude was evaluated. Participants were asked to indicate whether the stimulus
      was visibly flickering and to report their subjective level of discomfort. We
      then assessed visibly (41, 43, and 45Hz) vs. invisibly (61, 63, and 65Hz)
      flickering stimulus in an SSVEP-based BMI. Visual fatigue was assessed via the
      flicker test before and after operation of the BMI. RESULTS: Higher frequency
      stimuli reduced participants' subjective discomfort. Participants successfully
      controlled the SSVEP-based BMI using both the visibly and invisibly flickering
      stimuli (93.1% and 88.0%, respectively); the flicker test revealed a decrease in
      CFF (i.e., visual fatigue) under the visible condition only (-5.7%, P<0.001).
      CONCLUSIONS: The use of high-frequency visual stimuli above the CFF led to high
      classification accuracy and decreased visual fatigue in an SSVEP-based BMI.
      SIGNIFICANCE: High-frequency flicker stimuli above the CFF were able to induce
      SSVEPs and may prove useful in the development of BMI-based assistive products.

PMID- 25577408
TI  - Erratum to: Maximal oxygen consumption in healthy humans: theories and facts.

PMID- 25577409
TI  - Acute systemic insulin intolerance does not alter the response of the Akt/GSK-3
      pathway to environmental hypoxia in human skeletal muscle.
AB  - PURPOSE: To investigate how acute environmental hypoxia regulates blood glucose
      and downstream intramuscular insulin signaling after a meal in healthy humans.
      METHODS: Fifteen subjects were exposed for 4 h to normoxia (NOR) or to normobaric
      hypoxia (HYP, FiO2 = 0.11) in a randomized order 40 min after consumption of a
      high glycemic meal. A muscle biopsy from m. vastus lateralis and a blood sample
      were taken before (T0), after 1 h (T60) and 4 h (T240) in NOR or HYP and blood
      glucose levels were measured before exposure and every 30 min. RESULTS: In HYP,
      blood glucose was reduced 100 min (110.1 +/- 5.4 in NOR vs 89.5 +/- 4.7 mg dl(-1)
      in HYP) and 130 min (98.7 +/- 3.8 in NOR vs 85.6 +/- 4.9 mg dl(-1) in HYP) after
      completion of a meal, which resulted in an 83 % lower AUC in HYP compared to NOR
      (p = 0.006). This coincided with 40 % lower GLUT4 protein in the cytosolic
      fraction (p = 0.013) and a tendency to increase in the crude membrane fraction (p
      = 0.070) in HYP compared to NOR. At T240, blood glucose concentration was similar
      between HYP and NOR, whereas plasma insulin as well as phosphorylation of muscle
      Akt and GSK-3 was ~2-fold higher in HYP compared to NOR (p < 0.05). In contrast,
      Rac1 protein was less abundant in the membrane fraction in HYP compared to NOR (p
      = 0.003), reflecting lower activation. CONCLUSION: Acute environmental hypoxia
      initially reduced blood glucose response to a meal, possibly via an increase in
      GLUT4 abundance at the sarcolemmal membrane. Later on, whole body insulin
      intolerance developed independently of defects in conventional insulin signaling
      in skeletal muscle.

PMID- 25577410
TI  - [Microsurgical anatomy of perforating branches of anterior communicating artery].
AB  - INTRODUCTION: The anterior communicating artery (ACoA) gives perforating branches
      to the optic chiasma, the hypothalamus and the corpus callosum. Perforating
      branches are variable (number, direction). Nevertheless, their knowledge is
      crucial during surgery of this area to spare injuries leading to ischemic post
      operative complications. OBJECTIVE: The objective was to update the anatomical
      knowledge about perforating branches of the ACoA. METHODS: The study was led on a
      series of seven brains taken from human cadavers. An injection of latex neoprene
      was performed for every case. The region of interest was observed under operating
      microscope. Were examined: the length of the ACoA, its diameter, its orientation,
      its configuration and perforating branches (number and areas). RESULTS: Three
      cases on five presented with an anatomical variation at the level of the ACoA.
      The average length of AcoA was 2.1 millimeters (min: 2, max: 2.2). The average
      diameter of the ACoA was 1.67 mm (min: 1.1, max: 2.1). The average number of
      perforating branches was 4.2 (min: 2, max: 6). The presence of a median artery of
      the corpus callosum seemed to correlated with a low number of perforating
      branches. Branches supplying the optic chiasma seemed to be more numerous.

PMID- 25577411
TI  - Total glutamine synthetase levels in cerebrospinal fluid of Alzheimer's disease
      patients are unchanged.
AB  - Decreased cerebral protein and activity levels of glutamine synthetase (GS) have
      been reported for Alzheimer's disease (AD) patients. Using a recently established
      method, we quantified total GS levels in cerebrospinal fluid (CSF) from AD
      patients and control subjects. Furthermore, we investigated if total GS levels in
      CSF could differentiate AD from frontotemperal dementia and dementia with Lewy
      bodies patients. As we found no significantly altered total GS levels in any of
      the patient groups compared with control subjects, we conclude that levels of
      total GS in CSF have no diagnostic value for AD, dementia with Lewy bodies, or
      frontotemperal dementia. 

PMID- 25577412
TI  - Effects of aging on glutamate neurotransmission in the substantia nigra of Gdnf
      heterozygous mice.
AB  - Glial cell line-derived neurotrophic factor (GDNF) helps protect dopaminergic
      neurons in the nigrostriatal tract. Although the cause of nigrostriatal
      degeneration is unknown, one theory is that excess glutamate from the subthalamic
      nucleus results in excitotoxic events in the substantia nigra (SN). Because
      dopaminergic degeneration is accompanied by a reduction in GDNF, we examined
      glutamate neurotransmission in the SN using a Gdnf heterozygous mouse model
      (Gdnf(+/-)) at 8 and 12 months of age. At 8 months, Gdnf(+/-) mice have greater
      glutamate release and higher basal glutamate levels, which precede the SN
      dopaminergic degeneration observed at 12 months of age. However, at 12 months,
      Gdnf(+/-) mice have lower basal levels of glutamate and less glutamate release
      than wild-type mice. Also at 8 months, Gdnf(+/-) mice have lower levels of
      glutamate transporter-1 and greater glial fibrillary acidic protein levels in the
      SN compared with wild-type mice, differences that increase with age. These data
      suggest that reduced levels of GDNF induce excess glutamate release and
      dysregulation of glutamate transporter-1, causing excitotoxicity in the SN that
      precedes dopaminergic degeneration.

PMID- 25577414
TI  - Dental surgery in anticoagulated patients--stop the interruption.
AB  - In a literature review, the incidence and morbidity of bleeding complications
      after dental surgery in anticoagulated patients was compared with embolic
      complications when anticoagulation was interrupted. Over 99% of anticoagulated
      patients had no postoperative bleeding that required more than local hemostatic
      measures. Of more than 5431 patients undergoing more than 11,381 surgical
      procedures, with many patients at higher than present therapeutic intenational
      normalized ratio (INR) levels, only 31 (~0.6% of patients) required more than
      local hemostasis to control the hemorrhage; none died due to hemorrhage. Among at
      least 2673 patients whose warfarin dose was reduced or withdrawn for at least
      2775 visits for dental procedures, there were 22 embolic complications (0.8% of
      cessations), including 6 fatal events (0.2% of cessations). The embolic morbidity
      risk in patients whose anticoagulation is interrupted for dental surgery exceeds
      that of significant bleeding complications in patients whose anticoagulation is
      continued, even when surgery is extensive. Warfarin anticoagulation, therefore,
      should not be interrupted for most dental surgery. 

PMID- 25577413
TI  - Association between MAPT haplotype and memory function in patients with
      Parkinson's disease and healthy aging individuals.
AB  - Genetic variation is associated with differences in the function of the brain as
      well as its susceptibility to disease. The common H1 haplotypic variant of the
      microtubule-associated protein tau gene (MAPT) has been related to an increased
      risk for Parkinson's disease (PD). Furthermore, among PD patients, H1 homozygotes
      have an accelerated progression to dementia. We investigated the neurocognitive
      correlates of MAPT haplotypes using functional magnetic resonance imaging. Thirty
      seven nondemented patients with PD (19 H1/H1, 18 H2 carriers) and 40 age-matched
      controls (21 H1/H1, 19 H2 carriers) were scanned during performance of a picture
      memory encoding task. Behaviorally, H1 homozygosity was associated with impaired
      picture recognition memory in PD patients and control subjects. These impairments
      in the H1 homozygotes were accompanied by an altered blood-oxygen level-dependent
      response in the medial temporal lobe during successful memory encoding.
      Additional age-related differences in blood-oxygen level-dependent response were
      observed in the medial temporal lobes of H1 homozygotes with PD. These results
      suggest that common variation in MAPT is not only associated with the dementia of
      PD but also differences in the neural circuitry underlying aspects of cognition
      in normal aging. 

PMID- 25577415
TI  - Effect of bedtime on recurrent aphthous stomatitis in college students.
AB  - OBJECTIVE: In this study, we conducted a questionnaire-based survey at Sichuan
      University to investigate the potential effects of bedtime on recurrent aphthous
      stomatitis (RAS). STUDY DESIGN: An anonymous self-designed questionnaire was
      adopted to investigate the association between bedtime and RAS in college
      students at Sichuan University. Statistical analyses were used to identify risk
      factors for RAS and to explore the relationship between bedtime and RAS. RESULTS:
      One thousand six students were investigated. High frequency of colds (odds ratio
      [OR] 2.17; 95% confidence interval [CI] 1.52-3.10; P < .001) and bedtime after 11
      p.m. (OR 16.55; 95% CI 6.49-42.16; P < .001) were independent risk factors for
      RAS recurrence, but family history, stress, bad relationships with roommates, and
      gastrointestinal disease were not. Moreover, increased frequency of bedtime after
      11 p.m. (tau > 0; P < .05), as well as longer cumulative time from 11 p.m. to
      bedtime (R > 0; P < .05), was correlated with increased severity of ulcers.
      CONCLUSION: Bedtime after 11 p.m. not only served as an independent risk factor
      but both its frequency and cumulative time were also associated with severity of
      RAS in college students.

PMID- 25577416
TI  - The effects of voxel size on cone beam computed tomography images of the
      temporomandibular joints.
AB  - OBJECTIVES: This clinical study assesses the effect of cone beam computed
      tomography (CBCT) voxel size on the ability to detect osseous changes associated
      with degenerative disease of the temporomandibular joint (TMJ). The effect of
      voxel size on perceived CBCT image quality is also evaluated. STUDY DESIGN:
      Twenty-two patients presenting for TMJ imaging with suspected degenerative
      disease were imaged with the Carestream 9000 CBCT unit, using separate right and
      left joint acquisitions (n = 44). Images were archived at native and downsampled
      voxel resolutions of 76 MUm and 300 MUm, respectively. Three oral and
      maxillofacial radiologists evaluated the images for osseous changes, as well as
      image quality by using a visual analog scale. RESULTS: There was no statistically
      significant difference between the voxel sizes in the detection of TMJ
      osteoarthritic changes. The mean visual analog scale response did, however,
      differ significantly between the two groups (P = .02). CONCLUSIONS: Despite no
      improvement in diagnostic efficacy with a smaller voxel size, perceived image
      quality is consistently higher for images with greater spatial resolution.

PMID- 25577417
TI  - Accuracy of diagnosis of salivary gland tumors with the use of ultrasonography,
      computed tomography, and magnetic resonance imaging: a meta-analysis.
AB  - OBJECTIVE: To compare ultrasonography (US), computed tomography (CT), and
      magnetic resonance imaging (MRI) for clinical differential diagnosis in patients
      with salivary gland tumor (SGT). STUDY DESIGN: Six databases were used to search
      the literature published between 1982 and 2013. Histologic diagnosis was required
      as standard diagnosis. Pooled estimate for sensitivity, specificity, summary
      receiver-operating characteristic curve (SROC) and area under curve (AUC) were
      calculated and compared using STATA and Meta-Disc statistical software. RESULTS:
      Nineteen articles were included. Pooled sensitivity for US, CT, and MRI was 0.629
      (95% confidence interval [CI] 0.52-0.73), 0.830 (95% CI 0.74-0.90), and 0.807
      (95% CI 0.73-0.87), respectively; pooled specificity for US, CT, and MRI was
      0.920 (95% CI 0.89-0.94), 0.851 (95% CI 0.79-0.90), and 0.886 (95% CI 0.85-0.92),
      respectively. The AUC under SROC for US, CT, and MRI was 0.934 +/- 0.058, 0.912
      +/- 0.889, and 0.903 +/- 0.045, respectively. CONCLUSIONS: CT is recommended, as
      it is an effective imaging tool for differential diagnosis in patients with
      primary SGT, and MRI is suggested for differential diagnosis between benign and
      malignant GSTs because of its highest sensitivity and specificity.

PMID- 25577418
TI  - Role of intraoral color Doppler sonography in predicting delayed cervical lymph
      node metastasis in patients with early-stage tongue cancer: a pilot study.
AB  - OBJECTIVE: To clarify the intraoral color Doppler sonographic features of tongue
      cancer in relation to cervical lymph node metastasis. STUDY DESIGN: Thirty-one
      patients (24 men and 7 women; 32-87 years old; median 60.6 years) with T1-2 N0
      squamous cell carcinoma of the tongue were enrolled. Preoperative clinical
      information and sonographic findings were collected. Patients were followed up
      for 2 years or more, and the presence of delayed lymph node metastasis was
      investigated. Significant clinical and sonographic factors were evaluated in
      relation to lymph node metastasis. RESULTS: Significant differences in maximum
      and minimum tumor size, clinical type, tumor depth and thickness, shape of the
      invading front of the tumor, vascular index (VI) of the tumor area, and asymmetry
      of the VI of the deep lingual artery were observed between patients with cervical
      lymph node metastasis and those without. The areas under the curve (AUCs) of
      tumor thickness and the VI of the tumor area were 0.861 and 0.909, respectively,
      on receiver operating characteristic (ROC) curve analysis for predicting lymph
      node metastasis. The AUC for the VI showed a slightly higher value, although the
      difference was not significant (P = .532). CONCLUSIONS: Intraoral color Doppler
      sonography is recommended, as it may identify predictive factors of cervical
      lymph node metastasis.

PMID- 25577419
TI  - Can ultrasonography findings of tongue cancer really predict cervical lymph node
      metastasis?

PMID- 25577420
TI  - Necrotizing gingivostomatitis and osteonecrosis associated with antithyroid drug
      propylthiouracil therapy.
AB  - A 43-year-old Chinese female had been diagnosed with hyperthyroidism 15 years
      ago. She was recently administered 150 mg/day propylthiouracil (PTU). After 3
      weeks of PTU administration, she developed necrotizing stomatitis and
      osteonecrosis, most likely due to secondary effects from the PTU treatment. Her
      neutrophil count was reduced below normal to 0.24*10(9)/L but normalized after
      withdrawal of PTU therapy. About 1 month after onset, the patient came to our
      hospital and began to receive intravenous treatments of metronidazole and
      amoxicillin. Following review of her medical history and a series of clinical and
      laboratory examinations, the patient was diagnosed with secondary necrotizing
      gingivostomatitis and osteonecrosis possibly associated with PTU-induced
      agranulocytosis. One-year after treatment, the patient's oral manifestations
      remained unchanged. This case demonstrates the need for dental practitioners to
      more closely monitor oral symptoms in patients with hyperthyroidism treated with
      antithyroid drugs. 

PMID- 25577421
TI  - A novel technique for measurement of dentogingival tissue by cone beam computed
      tomography.
AB  - OBJECTIVES: To develop a novel technique to visualize dentogingival profiles by
      using cone beam computed tomography (CBCT) and to evaluate the accuracy of
      mucogingival tissue thickness measurements with CBCT, as compared with direct
      measurements in vitro. METHODS: A silicone matrix loaded with radiopaque
      impression material was prepared before performing CBCT on a patient. Two dry
      cadaver mandibles with simulated mucogingival tissue and six segmental cadaver
      jaws were used to assess the accuracy of mucogingival tissue thickness
      measurements directly and radiographically with CBCT images. Paired t tests were
      used to evaluate the intra- and interexaminer reliability and to compare the data
      between direct and CBCT imaging measurements at alpha = 0.05. RESULTS: No
      statistically significant differences were observed between direct and CBCT
      imaging measurements of simulated mucogingival tissue thickness in mandibular
      models and in cadaver jaws (P > .05). Results of direct measurements with
      simulated mucogingival tissue thickness indicated good intra- and interexaminer
      reliability. CONCLUSIONS: A novel technique was developed to obtain mucogingival
      tissue thickness data on the use of radiopaque impression materials and CBCT
      imaging. This new method provides a reliable visual dentogingival profile and a
      means to objective measurements.

PMID- 25577422
TI  - Climate change: what does it mean for people with multiple sclerosis?

PMID- 25577423
TI  - The authors respond.

PMID- 25577424
TI  - Transcriptional control of flavonoid biosynthesis by MYB-bHLH-WDR complexes.
AB  - Flavonoids are widely known for the colors they confer to plant tissues, their
      contribution to plant fitness and health benefits, and impact on food quality. As
      convenient biological markers, flavonoids have been instrumental in major genetic
      and epigenetic discoveries. We review recent advances in the characterization of
      the underlying regulatory mechanisms of flavonoid biosynthesis, with a special
      focus on the MBW (MYB-bHLH-WDR) protein complexes. These proteins are well
      conserved in higher plants. They participate in different types of controls
      ranging from fine-tuned transcriptional regulation by environmental factors to
      the initiation of the flavonoid biosynthesis pathway by positive regulatory
      feedback. The MBW protein complexes provide interesting models for investigating
      developmentally or environmentally controlled transcriptional regulatory
      networks. 

PMID- 25577425
TI  - Constrictive pericarditis: the mitral annulus remains paradoxical.

PMID- 25577426
TI  - Location of the culprit coronary lesion and its association with delay in door-to
      balloon time (from a multicenter registry of primary percutaneous coronary
      intervention).
AB  - Current guidelines recommend shorter door-to-balloon times (DBTs) (<90 minutes)
      for patients with ST-elevation myocardial infarction (STEMI). Clinical factors,
      including patient or hospital characteristics, associated with prolonged DBT have
      been identified, but angiographic variables such as culprit lesion location have
      not been thoroughly investigated. We aimed to evaluate the effect of culprit
      artery location on DBT of patients with STEMI who underwent percutaneous coronary
      intervention (PCI). Data were analyzed from 1,725 patients with STEMI who
      underwent PCI from August 2008 to March 2014 at 16 Japanese hospitals. Patients
      were divided into 3 groups according to culprit artery location, right coronary
      artery (RCA), left anterior descending artery (LAD), and left circumflex artery
      (LC), and associations with DBT were assessed. The LC group had a trend toward a
      longer DBT among the 3 groups (97.1 [RCA] vs 98.1 [LAD] vs 105.1 [LC] minutes; p
      = 0.058). In-hospital mortality was also significantly higher in patients with a
      left coronary artery lesion (3.5% [RCA] vs 6.3% [LAD] vs 5.4% [LC]; p = 0.041).
      In-hospital mortality for patients with DBT >90 minutes was significantly higher
      compared with patients with DBT <=90 minutes (6.5% vs 3.6%; p = 0.006).
      Multivariate logistic regression analysis revealed that the LC location was an
      independent predictor for DBT >90 minutes (odds ratio, 1.45; 95% confidence
      interval, 1.04 to 2.01; p = 0.028). In conclusion, LC location was an independent
      predictor of longer DBT. The difficulties in diagnosing LC-related STEMI need
      further evaluation.

PMID- 25577427
TI  - Molecular cloning and expression analysis of dmrt1 and sox9 during gonad
      development and male reproductive cycle in the lambari fish, Astyanax
      altiparanae.
AB  - BACKGROUND: The dmrt1 and sox9 genes have a well conserved function related to
      testis formation in vertebrates, and the group of fish presents a great diversity
      of species and reproductive mechanisms. The lambari fish (Astyanax altiparanae)
      is an important Neotropical species, where studies on molecular level of sex
      determination and gonad maturation are scarce. METHODS: Here, we employed
      molecular cloning techniques to analyze the cDNA sequences of the dmrt1 and sox9
      genes, and describe the expression pattern of those genes during development and
      the male reproductive cycle by qRT-PCR, and related to histology of the gonad.
      RESULTS: Phylogenetic analyses of predicted amino acid sequences of dmrt1 and
      sox9 clustered A. altiparanae in the Ostariophysi group, which is consistent with
      the morphological phylogeny of this species. Studies of the gonad development
      revealed that ovary formation occurred at 58 days after hatching (dah), 2 weeks
      earlier than testis formation. Expression studies of sox9 and dmrt1 in different
      tissues of adult males and females and during development revealed specific
      expression in the testis, indicating that both genes also have a male-specific
      role in the adult. During the period of gonad sex differentiation, dmrt1 seems to
      have a more significant role than sox9. During the male reproductive cycle dmrt1
      and sox9 are down-regulated after spermiation, indicating a role of these genes
      in spermatogenesis. CONCLUSIONS: For the first time the dmrt1 and sox9 were
      cloned in a Characiformes species. We show that both genes have a conserved
      structure and expression, evidencing their role in sex determination, sex
      differentiation and the male reproductive cycle in A. altiparanae. These findings
      contribute to a better understanding of the molecular mechanisms of sex
      determination and differentiation in fish.

PMID- 25577428
TI  - Does renal dysfunction modify the effect of intravenous thrombolysis for acute
      ischemic stroke within 4.5 hours of onset? A multicenter observational study.
AB  - BACKGROUND: About one third of stroke patients have renal dysfunction. Effect of
      renal dysfunction on outcome of intravenous thrombolysis (IVT) for acute ischemic
      stroke (AIS) has not been determined in Asia using patients without IVT as
      comparators. The aim of this study was to examine the interaction between renal
      dysfunction and IVT on the outcomes in AIS patients admitted within 4.5 hours of
      onset in a multicenter stroke registry of Taiwan. METHODS: We identified all
      consecutive AIS patients admitted within 4.5 hours of onset between 2007 and
      2013. Renal dysfunction was defined by an estimated glomerular filtration rate
      less than 60 mL/minute/1.73 m(2) on initial admission. Patients older than 80
      years of age and a National Institute of Health Stroke Scale score less than 4 or
      greater than 25 were excluded. The primary outcome was a modified Rankin Scale
      score 3-6 at 3 months. We determined the effect of IVT and renal dysfunction on
      outcome in a multivariate analysis. RESULTS: Of the 929 patients analyzed, 39%
      had renal dysfunction, and 51% received IVT. Primary outcomes occurred in 45%
      versus 41% of patients with and without renal dysfunction, respectively, (P =
      .197). In a multivariate analysis, the odds ratios (95% confidence interval; P
      value) of IVT and renal dysfunction for primary outcome were .70 (.51-.96; P =
      .029) and .97 (.71-1.33; P = .865), respectively. No significant interaction was
      noted between IVT and renal dysfunction (P = .218). CONCLUSIONS: Renal
      dysfunction did not modify the effect of IVT for AIS and should not be a reason
      for withholding treatment from otherwise-eligible patients.

PMID- 25577429
TI  - Knowledge regarding oral anticoagulation therapy among patients with stroke and
      those at high risk of thromboembolic events.
AB  - BACKGROUND: Apart from atrial fibrillation, indications for oral anticoagulation
      common in our clinical practice include rheumatic heart disease and mechanical
      heart valve replacement. Evaluation of current patient knowledge regarding oral
      anticoagulation therapy (OAT) is the first step in improving the quality of
      anticoagulation therapy and patient care. The aim of the present study was to
      assess the knowledge regarding OAT among patients with stroke and those at high
      risk of thromboembolic events in a tertiary care hospital in India. METHODS: A
      descriptive cross-sectional design was used; 240 patients on OAT because of
      various indications (mechanical heart valve replacement, rheumatic heart disease,
      atrial fibrillation, and stroke) attending the neurology and cardiology
      outpatient clinics and inpatient services were recruited. A structured self
      developed questionnaire was used to assess the knowledge in these patients.
      RESULTS: Most patients (62.9%) were ignorant about the target prothrombin
      time/international normalized ratio (PT/INR) levels with only 30% having their
      recent INR within the target range; 50% of the patients had a poor knowledge
      score, and the knowledge gap was most prominent in the domains of dietary
      interactions followed by drug interactions, adverse effects, and PT/INR
      monitoring. Knowledge score also had a significant association with gender,
      education, monthly income, and place of residence (P < .05). CONCLUSION:
      Patient's knowledge about OAT was suboptimal. The findings support the need for
      educational interventions to improve the knowledge regarding OAT and, thereby,
      achieve an appropriate and safe secondary prevention of stroke.

PMID- 25577430
TI  - [Keratitis due to foreign bodies from a processionary caterpillar nest].

PMID- 25577431
TI  - [Managing antithrombotic therapy in vitreoretinal surgery].
AB  - Given the growing number of patients on antithrombotic therapy we are
      increasingly confronted with the management of this therapy before, during and
      after vitreoretinal surgery. In the absence of a consensus, the decision to
      withdraw antithrombotic therapy is based on the cardiovascular thromboembolism
      risk versus the theoretical risk of bleeding if the antithrombotic treatment is
      continued. As suggested by the literature, antiplatelet therapy (acetylsalicylic
      acid or clopidogrel) may be safely continued for vitreoretinal surgery, including
      retinal detachment repair. However, the risk/benefit ratio for patients being
      treated with two antiplatelet therapies is unknown. It appears that an
      International Normalized Ratio (INR) less than 3 for patients treated with
      anticoagulant therapy does not increase the perioperative risk of ocular
      bleeding. This risk has not been evaluated in patients treated by new
      antithrombotic therapies (prasugrel, ticagrelor as antiplatelet medication, or
      dabigatran, rivaroxaban, apixaban as anticoagulant therapy), and there is a need
      to study it further. 

PMID- 25577432
TI  - [Ophthalmology and urban underprivileged. Experience of 150 patients].
AB  - INTRODUCTION: An ophthalmology consultation was carried out at the Hotel-Dieu to
      facilitate eye care in underprivileged patients referred by the general medicine
      PASS (socialized health care) of the same hospital. MATERIALS AND METHODS: The
      files of 150 consecutive patients examined by a single ophthalmologist between
      January 2012 and June 2013 were reviewed. A standard examination was performed in
      these patients, sent with a consult sheet, to which a response was sent to PASS.
      As necessary, prescriptions were also written for the patients. RESULTS: Most
      patients (89/150) were immigrants from sub-Saharan Africa. Additionally, there
      were 25 Europeans with only 5 French, and 17 Asians. The mean age was 41 years
      with 90 men (mean age 43) and 60 women (mean age 36). The most common systemic
      diseases observed were hypertension, (13), diabetes (6), and hepatitis (6). The
      mean best-corrected visual acuity (129 patients) was a slightly more than 8/10
      (16/20) (measurable in 143 patients). Refractive state (measured in 129 patients)
      was myopia (46), hyperopia (41), presbyopia (isolated in 12 cases), astigmatism
      (26), and emmetropia (28). Optical correction was prescribed in 87 patients. The
      main pathological conditions included pingueculae (19), cataracts (19), trauma
      (13) of which 4 patients were monocular, and pterygia (9). DISCUSSION AND
      CONCLUSION: Refractive errors were the main abnormality observed in these
      underprivileged patients. Apart from cataract as a pathologic condition observed
      in the general population, more characteristic of this sub-Saharan population
      were pinguecula, pterygium and trauma. This study highlights the more general
      question of access to eye care for all underprivileged patients.

PMID- 25577433
TI  - Diagnostic delay in adult-onset dystonia: data from an Italian movement disorder
      center.
AB  - Adult-onset dystonia (AOD) may manifest in focal forms (as blepharospasm,
      oromandibular dystonia, cervical dystonia, laryngeal dystonia, and hand dystonia)
      or in segmental forms. Time from onset of dystonia to diagnosis can be an
      indicator of the quality of care received during the diagnosis of AOD, likely
      reflecting factors associated with both the patient and their health system.
      Three previously reported single-center studies showed that diagnosis of AOD may
      be delayed for several years. Here, we examined the time lapse between onset and
      diagnosis in patients with different forms of AOD from an Italian movement
      disorder center. We found the time lapse between dystonia onset and diagnosis was
      very long for patients who developed AOD before 1980; and even in the most recent
      years reaching a correct diagnosis required more than year in almost half of
      cases. Our results suggest that the delay in diagnosis of adult-onset focal and
      segmental dystonia has improved over time, but remains unacceptable. The findings
      are a promising indicator of improvements in care of this uncommon disorder.
      However, education of patients and doctors is still needed. 

PMID- 25577434
TI  - Shifted Hamming distance: a fast and accurate SIMD-friendly filter to accelerate
      alignment verification in read mapping.
AB  - MOTIVATION: Calculating the edit-distance (i.e. minimum number of insertions,
      deletions and substitutions) between short DNA sequences is the primary task
      performed by seed-and-extend based mappers, which compare billions of sequences.
      In practice, only sequence pairs with a small edit-distance provide useful
      scientific data. However, the majority of sequence pairs analyzed by seed-and
      extend based mappers differ by significantly more errors than what is typically
      allowed. Such error-abundant sequence pairs needlessly waste resources and
      severely hinder the performance of read mappers. Therefore, it is crucial to
      develop a fast and accurate filter that can rapidly and efficiently detect error
      abundant string pairs and remove them from consideration before more
      computationally expensive methods are used. RESULTS: We present a simple and
      efficient algorithm, Shifted Hamming Distance (SHD), which accelerates the
      alignment verification procedure in read mapping, by quickly filtering out error
      abundant sequence pairs using bit-parallel and SIMD-parallel operations. SHD only
      filters string pairs that contain more errors than a user-defined threshold,
      making it fully comprehensive. It also maintains high accuracy with moderate
      error threshold (up to 5% of the string length) while achieving a 3-fold speedup
      over the best previous algorithm (Gene Myers's bit-vector algorithm). SHD is
      compatible with all mappers that perform sequence alignment for verification.

PMID- 25577435
TI  - ENViz: a Cytoscape App for integrated statistical analysis and visualization of
      sample-matched data with multiple data types.
AB  - ENViz (Enrichment Analysis and Visualization) is a Cytoscape app that performs
      joint enrichment analysis of two types of sample matched datasets in the context
      of systematic annotations. Such datasets may be gene expression or any other high
      throughput data collected in the same set of samples. The enrichment analysis is
      done in the context of pathway information, gene ontology or any custom
      annotation of the data. The results of the analysis consist of significant
      associations between profiled elements of one of the datasets to the annotation
      terms (e.g. miR-19 was associated to the cell-cycle process in breast cancer
      samples). The results of the enrichment analysis are visualized as an interactive
      Cytoscape network.

PMID- 25577436
TI  - The Overestimation Phenomenon in a Skill-Based Gaming Context: The Case of March
      Madness Pools.
AB  - Over 100 million people are estimated to take part in the NCAA Men's Basketball
      Tournament Championship bracket contests. However, relatively little is known
      about consumer behavior in skill-based gaming situations (e.g., sports betting).
      In two studies, we investigated the overestimation phenomenon in the "March
      Madness" context. In Study 1 (N = 81), we found that individuals who were allowed
      to make their own predictions were significantly more optimistic about their
      performance than individuals who did not make their own selections. In Study 2 (N
      = 197), all subjects participated in a mock competitive bracket pool. In line
      with the illusion of control theory, results showed that higher self-ratings of
      probability of winning significantly increased maximum willingness to wager but
      did not improve actual performance. Lastly, perceptions of high probability of
      winning significantly contributed to consumers' enjoyment and willingness to
      participate in a bracket pool in the future. 

PMID- 25577437
TI  - Links between mechanical behavior of cancellous bone and its microstructural
      properties under dynamic loading.
AB  - Previous studies show that in vivo assessment of fracture risk can be achieved by
      identifying the relationships between microarchitecture description from clinical
      imaging and mechanical properties. This study demonstrates that results obtained
      at low strain rates can be extrapolated to loadings with an order of magnitude
      similar to trauma such as car crashes. Cancellous bovine bone specimens were
      compressed under dynamic loadings (with and without confinement) and the
      mechanical response properties were identified, such as Young's modulus, ultimate
      stress, ultimate strain, and ultimate strain energy. Specimens were previously
      scanned with pQCT, and architectural and structural microstructure properties
      were identified, such as parameters of geometry, topology, connectivity and
      anisotropy. The usefulness of micro-architecture description studied was in
      agreement with statistics laws. Finally, the differences between dynamic confined
      and non-confined tests were assessed by the bone marrow influence and the
      cancellous bone response to different boundary conditions. Results indicate that
      architectural parameters, such as the bone volume fraction (BV/TV), are as strong
      determinants of mechanical response parameters as ultimate stress at high strain
      rates (p-value<0.001). This study reveals that cancellous bone response at high
      strain rates, under different boundary conditions, can be predicted from the
      architectural parameters, and that these relations with mechanical properties can
      be used to make fracture risk prediction at a determined magnitude. 

PMID- 25577438
TI  - Effect of anatomical landmark perturbation on mean helical axis parameters of in
      vivo upper costovertebral joints.
AB  - The literature concerning quantification of costovertebral joint (CVJ) motion
      under in vivo conditions is scarce. Most papers concerning this topic are related
      to ex vivo loading conditions. In vivo protocols are available from the
      literature to determine rib and vertebra kinematics but new developments are
      needed to improve data processing concerning CVJ behaviour obtained from discrete
      breathing positions showing limiting ranges-of-motion and sensitive to noise.
      Data from previous work were used to implement a method analyzing mean helical
      axis (MHA) and pivot point parameters of the CVJ complexes. Several levels of
      noises were estimated within Monte-Carlo simulations to optimize MHA results. MHA
      parameters were then used to transform and define a CVJ-specific local coordinate
      system. This study proposes an improvement for CVJ kinematics processing and
      description from in vivo data obtained from computed tomography. This methodology
      emphasizes the possibility to work with variability of MHA parameters using Monte
      Carlo procedures on anatomical landmark coordinates and to define a local
      coordinate system from this particular joint behaviour. Results from the CVJ
      joint model are closer to a hinge joint (secondary motions inferior to 3 degrees
      ) when anatomical frames are expressed from MHA orientation. MHA orientation and
      position data obtained from the proposed method are relevant according to angular
      dispersion obtained (from 7.5 degrees  to 13.9 degrees ) and therefore relevant
      to define behaviour of CVJ. 

PMID- 25577439
TI  - A critical role for transcription factor Smad4 in T cell function that is
      independent of transforming growth factor beta receptor signaling.
AB  - Transforming growth factor-beta (TGF-beta) suppresses T cell function to maintain
      self-tolerance and to promote tumor immune evasion. Yet how Smad4, a
      transcription factor component of TGF-beta signaling, regulates T cell function
      remains unclear. Here we have demonstrated an essential role for Smad4 in
      promoting T cell function during autoimmunity and anti-tumor immunity. Smad4
      deletion rescued the lethal autoimmunity resulting from transforming growth
      factor-beta receptor (TGF-betaR) deletion and compromised T-cell-mediated tumor
      rejection. Although Smad4 was dispensable for T cell generation, homeostasis, and
      effector function, it was essential for T cell proliferation after activation in
      vitro and in vivo. The transcription factor Myc was identified to mediate Smad4
      controlled T cell proliferation. This study thus reveals a requirement of Smad4
      for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current
      paradigm. It highlights a TGF-betaR-independent role for Smad4 in promoting T
      cell function, autoimmunity, and anti-tumor immunity.

PMID- 25577440
TI  - Liver-resident macrophage necroptosis orchestrates type 1 microbicidal
      inflammation and type-2-mediated tissue repair during bacterial infection.
AB  - Kupffer cells, the phagocytes of fetal origin that line the liver sinusoids, are
      key contributors of host defense against enteroinvasive bacteria. Here, we found
      that infection by Listeria monocytogenes induced the early necroptotic death of
      Kupffer cells, which was followed by monocyte recruitment and an anti-bacterial
      type 1 inflammatory response. Kupffer cell death also triggered a type 2 response
      that involved the hepatocyte-derived alarmin interleukin-33 (IL-33) and basophil
      derived interleukin-4 (IL-4). This led to the alternative activation of the
      monocyte-derived macrophages recruited to the liver, which thereby replaced
      ablated Kupffer cells and restored liver homeostasis. Kupffer cell death is
      therefore a key signal orchestrating type 1 microbicidal inflammation and type-2
      mediated liver repair upon infection. This indicates that beyond the classical
      dichotomy of type 1 and type 2 responses, these responses can develop
      sequentially in the context of a bacterial infection and act interdependently,
      orchestrating liver immune responses and return to homeostasis, respectively.

PMID- 25577442
TI  - Image Feature Determinants of Global and Segmental Circumferential Ventricular
      Strain From Cine CMR.

PMID- 25577441
TI  - Splenic metabolic activity predicts risk of future cardiovascular events:
      demonstration of a cardiosplenic axis in humans.
AB  - OBJECTIVES: This study sought to determine whether splenic activation after acute
      coronary syndrome (ACS) is linked to leukocyte proinflammatory remodeling and
      whether splenic activity independently predicts the risk of cardiovascular
      disease (CVD) events. BACKGROUND: Pre-clinical data suggest the existence of a
      cardiosplenic axis, wherein activation of hematopoietic tissues (notably in the
      spleen) results in liberation of proinflammatory leukocytes and accelerated
      atherosclerotic inflammation. However, it is presently unknown whether a
      cardiosplenic axis exists in humans and whether splenic activation relates to CVD
      risk. METHODS: (18)F-fluorodeoxyglucose ((18)FDG)-positron emission tomography
      (PET) imaging was performed in 508 individuals across 2 studies. In the first
      study, we performed FDG-PET imaging in 22 patients with recent ACS and 22 control
      subjects. FDG uptake was measured in spleen and arterial wall, whereas
      proinflammatory gene expression of circulating leukocytes was assessed by
      quantitative real-time polymerase chain reaction. In a second study, we examined
      the relationship between splenic tissue FDG uptake with subsequent CVD events
      during follow-up (median 4 years) in 464 patients who previously had undergone
      FDG-PET imaging. RESULTS: Splenic activity increased after ACS and was
      significantly associated with multiple indices of inflammation: 1) up-regulated
      gene expression of proinflammatory leukocytes; 2) increased C-reactive protein;
      and 3) increased arterial wall inflammation (FDG uptake). Moreover, in the second
      study, splenic activity (greater than or equal to the median) was associated with
      an increased risk of CVD events (hazard ratio [HR]: 3.3; 95% confidence interval
      [CI]: 1.5 to 7.3; p = 0.003), which remained significant after adjustment for CVD
      risk factors (HR: 2.26; 95% CI: 1.01 to 5.06; p = 0.04) and for arterial FDG
      uptake (HR: 2.68; 95% CI: 1.5 to 7.4; p = 0.02). CONCLUSIONS: Our findings
      demonstrate increased splenic metabolic activity after ACS and its association
      with proinflammatory remodeling of circulating leukocytes. Moreover, we observed
      that metabolic activity of the spleen independently predicted risk of subsequent
      CVD events. Collectively, these findings provide evidence of a cardiosplenic axis
      in humans similar to that shown in pre-clinical studies.

PMID- 25577443
TI  - Fate of Coronary Chronic Total Occlusion Recanalization via Subintimal Tracking
      With Bioresorbable Vascular Scaffolds: A Temporary Cage for a Permanent New
      Lumen?

PMID- 25577444
TI  - Impaired RV global longitudinal strain is associated with poor long-term clinical
      outcomes in patients with acute inferior STEMI.
AB  - OBJECTIVES: The aim of this study was to assess the long-term prognostic value of
      the global longitudinal strain of the right ventricle (GLSRV) in patients with
      inferior ST-segment elevation myocardial infarction (STEMI) who underwent primary
      percutaneous coronary intervention (PCI). BACKGROUND: RV systolic dysfunction is
      an important prognostic factor in patients with inferior STEMI. METHODS: All
      consecutive inferior STEMI patients were included from January 2005 to December
      2013. RV systolic function was analyzed with GLSRV using velocity vector imaging
      (Siemens, Mountain View, California), as well as conventional echocardiographic
      indices, including right ventricular fractional area change (RVFAC) and tricuspid
      annular plane systolic excursion (TAPSE). RESULTS: We analyzed a total of 282
      consecutive inferior STEMI patients (212 men, age 63 +/- 13 years) treated with
      primary PCI. During the follow-up period (54 +/- 35 months), 59 patients (21%)
      had 1 or more major adverse cardiovascular event (MACE) (43 deaths, 7 nonfatal
      MI, 4 target vessel revascularization, and 6 heart failure admission). The best
      cutoff value of GLSRV for the prediction of MACE was >=-15.5% (area under the
      curve = 0.742, p < 0.001) with a sensitivity of 73% and a specificity of 65%.
      GLSRV showed better sensitivity and specificity than RVFAC and TAPSE. After
      multivariate analysis, GLSRV showed a higher c-statistic value (0.770) than RVFAC
      (0.749) and TAPSE (0.751) in addition to age, Killip class, troponin-I, left
      ventricular (LV) ejection fraction and RV infarction. Patients with GLSRV>=-15.5%
      showed significantly lower 5-year survival rate (74 +/- 5% vs. 89 +/- 3%, p <
      0.001) and lower MACE-free survival rate (64 +/- 5% vs. 87 +/- 3%, p < 0.001)
      than the control group. CONCLUSIONS: Because GLSRV showed additive predictive
      value to age and LV function, it can be the strongest parameter of RV systolic
      function evaluating the prognosis after PCI for acute inferior STEMI particularly
      in patients with preserved LV function.

PMID- 25577445
TI  - Combined IVUS and NIRS detection of fibroatheromas: histopathological validation
      in human coronary arteries.
AB  - OBJECTIVES: This study assessed grayscale intravascular ultrasound (IVUS) and
      near-infrared spectroscopy (NIRS) detection of a histological fibroatheroma (FA).
      BACKGROUND: NIRS-detected, lipid-rich plaques (LRPs) and IVUS-detected attenuated
      plaques are considered to be vulnerable. METHODS: IVUS-attenuated plaque and NIRS
      LRP (yellow or tan block chemogram) were compared with histopathology in 1,943
      sections of 103 coronary arteries from 56 autopsied hearts. RESULTS: IVUS
      superficial attenuation and NIRS-LRP showed a similar high specificity of
      approximately 95%, whereas IVUS-superficial attenuation alone had a poor
      sensitivity (vs. NIRS-LRP) in detecting FAs (36% vs. 47%; p = 0.001). Compared
      with FA sections with superficial attenuation, FA sections without superficial
      attenuation had a smaller plaque burden (57.1% vs. 67.7%), a larger arc of
      calcium (79.7 degrees  vs. 16.8 degrees ), and a lower prevalence of a >=20%
      histological necrotic core (28% vs. 50%) or late FA (14% vs. 37%; all p < 0.05).
      Compared with FA sections with NIRS-LRP, FA sections without NIRS-LRP showed a
      smaller plaque burden (58.0% vs. 63.3%) and a lower prevalence of a >=20%
      necrotic core (27% vs. 46%). Conversely, non-FAs with NIRS-LRP (vs. non-FAs
      without LRP) showed a larger plaque burden (55.1% vs. 46.3%), a greater
      prevalence of a >=20% histological lipid pool (34% vs. 5%), and mostly
      pathological intimal thickening (50%) or fibrocalcific plaque (33%). When
      sections showed either IVUS attenuation or NIRS-LRP, the sensitivity for
      predicting a FA was significantly higher compared with IVUS attenuation alone
      (63% vs. 36%; p < 0.001) or NIRS-LRP alone (63% vs. 47%; p < 0.001). When
      sections showed both IVUS attenuation and NIRS-LRP, the positive predictive value
      improved compared with IVUS attenuation alone (84% vs. 66%; p < 0.001) or NIRS
      LRP alone (84% vs. 65%; p < 0.001). CONCLUSIONS: NIRS-LRP was more accurate than
      IVUS for predicting plaque containing a necrotic core or a large lipid pool, and
      the combination was more accurate than either alone.

PMID- 25577447
TI  - How to define end-diastole and end-systole?: Impact of timing on strain
      measurements.
AB  - OBJECTIVES: This study aimed to investigate to what extent timing definitions
      influence strain measurements and which surrogates are reliable and feasible to
      define end-diastole (ED) and end-systole (ES) during speckle-tracking (STI)
      analysis. BACKGROUND: Current STI-based strain measurements are highly automated.
      It remains unclear when a particular analysis software defines the zero baseline
      and the systolic strain measurement position. METHODS: A total of 60 subjects (20
      healthy volunteers, 20 patients with coronary artery disease, and 20 patients
      with typical left bundle-branch block) underwent a complete echocardiographic
      examination. In one-half of them, a real M-mode through the mitral valve was
      acquired for each electrocardiographic (ECG) lead of the echo machine. Timing of
      peak R and automatic ECG trigger were compared with mitral valve closure for
      every electrode. Mitral and aortic valve closure, as observed in the apical 3
      chamber view, served as reference for ED and ES. With the use of these
      references, end-systolic global longitudinal strain (ES-GLS) and end-systolic
      segmental longitudinal strain (ES-SLS) longitudinal end-systolic strain were
      measured at baseline and after changing the definition of either ED or ES by +/-4
      frames. Furthermore, strain and volume curves derived from the same tracking, as
      well as the Doppler interrogation of the valves, were compared with the
      references. RESULTS: Depending on the selected lead, timing of the ECG-derived
      time markers changed considerably compared with mitral valve closure. Changing
      the definition of ED and ES resulted in significantly different ES-GLS and ES-SLS
      values in all subjects. ES-SLS in dyssynchronous hearts showed the highest
      sensitivity to timing definition. From all methods, spectral Doppler was the most
      reliable time marker in all subjects (p > 0.05). CONCLUSIONS: Exact temporal
      definition of ED and ES has a major impact on the accuracy of strain
      measurements. After direct observation of the valves, Doppler evaluation is the
      best means for characterizing ED and ES for STI analysis.

PMID- 25577446
TI  - Increased extracellular volume and altered mechanics are associated with LVH in
      hypertensive heart disease, not hypertension alone.
AB  - OBJECTIVES: The goal of this study was to assess the relationship among
      extracellular volume (ECV), native T1, and systolic strain in hypertensive
      patients with left ventricular hypertrophy (HTN LVH), hypertensive patients
      without LVH (HTN non-LVH), and normotensive controls. BACKGROUND: Diffuse
      myocardial fibrosis in HTN LVH patients, as reflected by increased ECV and native
      T1, may be an underlying mechanism contributing to increased cardiovascular risk
      compared with HTN non-LVH subjects and controls. Furthermore, increased diffuse
      fibrosis in HTN LVH subjects may be associated with reduced peak systolic and
      early diastolic strain rate compared with the other 2 groups. METHODS: T1 mapping
      was performed in 20 HTN LVH (mean age, 55 +/- 11 years), 23 HTN non-LVH (mean
      age, 61 +/- 12 years), and 22 control subjects (mean age, 54 +/- 7 years) on a
      Siemens 1.5-T Avanto (Siemens Healthcare, Erlangen, Germany) using a previously
      validated modified look-locker inversion-recovery pulse sequence. T1 was measured
      pre-contrast and 10, 15, and 20 min after injection of 0.15 mmol/kg gadopentetate
      dimeglumine, and the mean ECV and native T1 were determined for each subject.
      Measurement of circumferential strain parameters were performed using cine
      displacement encoding with stimulated echoes. RESULTS: HTN LVH subjects had
      higher native T1 compared with controls (p < 0.05). HTN LVH subjects had higher
      ECV compared with HTN non-LVH subjects and controls (p < 0.05). Peak systolic
      circumferential strain and early diastolic strain rates were reduced in HTN LVH
      subjects compared with HTN non-LVH subjects and controls (p < 0.05). Increased
      levels of ECV and native T1 were associated with reduced peak systolic and early
      diastolic circumferential strain rate across all subjects. CONCLUSIONS: HTN LVH
      patients had higher ECV, longer native T1 and associated reduction in peak
      systolic circumferential strain, and early diastolic strain rate compared with
      HTN non-LVH and control subjects. Measurement of ECV and native T1 provide a
      noninvasive assessment of diffuse fibrosis in hypertensive heart disease.

PMID- 25577448
TI  - Noise level measurement, a new method to evaluate effectiveness of sedation in
      pediatric dentistry.
AB  - OBJECTIVES: Pediatric dentists perform moderate sedation frequently to facilitate
      dental treatment in uncooperative children. Assessing the depth and quality of
      sedation is an important factor in the clinical utilization of moderate sedation.
      We aimed to determine if the level of noise, created by the children who are
      undergoing moderate sedation during dental procedures, could be used as a
      nonsubjective measurement of the depth of sedation and compare it to the Ohio
      State Behavior Rating Score (OSBRS). METHODS: Following Institutional Review
      Board approval and after receiving informed consent, we studied 51 children with
      a mean age of 4.2 years and average weight of 18.5 kg, who were undergoing
      restorative or extractive dental procedures, requiring moderate sedation.
      Sedation efficacy was assessed using OSBRS at several stages of the procedure.
      The noise level was measured by using a NoisePRO logging device to record the
      noise level at a rate of every second throughout the procedure. RESULTS: The
      depth of sedation assessed by OSBRS during the operative procedure was
      significantly correlated with noise level. The act of administering the local
      anesthesia and the operative procedure itself were two phases of the encounter
      that were significantly associated with higher OSBRS as well as noise levels.
      CONCLUSION: Measurement of noise level can be used as an effective guide to
      quantify the depth of sedation at different stages of the dental procedure. It is
      a nonsubjective and continuous measurement, which could be useful in clinical
      practice for the administration of moderate sedation during dental procedures. By
      using noise level analysis we are able to determine successful, poor, and failed
      sedation outcome.

PMID- 25577449
TI  - Beta-2 microglobulin predicts the outcome after autologous stem cell
      transplantation in non-Hodgkin lymphoma.
AB  - Autologous stem cell transplantation (ASCT) is an established therapeutic
      modality in the treatment of lymphomas, especially in the relapse setting. In the
      present study, we aimed to define pretransplantation factors including Beta-2
      microglobulin (beta2m) that influence outcomes following ASCT in patients with
      non-Hodgkin lymphoma (NHL). We analyzed retrospectively 78 NHL patients who had
      undergone ASCT from August 2010 to January 2013. The 2-year overall survival (OS)
      was 70% and the progression-free survival (PFS) was 60%. While remission status
      less than complete remission (CR) emerged to be a poor prognostic factor for OS
      in univariate analysis, high beta2m levels and comorbidity indices revealed to be
      independent poor risk factors for both OS and PFS. The present study demonstrated
      that even if the patient is in CR before ASCT if he has high beta2m, the 2-year
      OS decreases from 100% to 49%. Moreover, lymphopenia for the first time was
      demonstrated to predict PFS in ASCT in NHL patients. Our findings suggest that
      beta2m at transplantation predict the outcome after ASCT in NHL and further
      investigation with larger sample sizes is warranted.

PMID- 25577450
TI  - Guest editor bio: remembering the past personal lifetime leaders.

PMID- 25577452
TI  - Delta-aminolevulinic acid-induced fluorescence unmasks biological intratumoral
      heterogeneity within histologically homogeneous areas of malignant gliomas.

PMID- 25577451
TI  - Treatment of large thoracic and lumbar paraspinal schwannoma.
AB  - BACKGROUND: Paraspinal neurogenic tumors usually expand into the mediastinum and
      retroperitoneum and can reach a considerable size before they become symptomatic.
      Such large tumors are rare. We describe 14 cases of large schwannomas (>2.5 cm o)
      with mild and late onset of symptoms, which were treated with total surgical
      resection through a single-approach surgery. METHODS: In 2013 14 patients with
      paraspinal large schwannomas were treated in our institutions. Data were analyzed
      retrospectively. Magnetic resonance imaging (MRI) showed lesions suspicious for a
      paraspinal schwannoma with partial intraforaminal growth. In case of ambiguity
      regarding tumor dignity, a needle biopsy was performed before final treatment.
      Three different approaches and their indications were discussed. RESULTS:
      Fourteen patients (7 female and 7 male, ages 18-58 years, mean: 39.8 years)
      requiring surgical exploration because of a thoracic (6) or lumbar/lumbosacral
      (8) lesion were treated in our institutions. Two patients received CT-guided
      needle biopsy preoperatively. Complete resection of the schwannoma was possible
      through a mini-thoracotomy in 1 case (7 %), a retroperitoneal approach in 2 cases
      (14 %), and dorsal interlaminar and intercostal fenestration in 11 cases (79 %).
      Histological examination revealed the diagnosis of schwannoma (WHO grade I) in
      all cases except one with neurofibroma (WHO grade I). There were no major
      complications in any case. CONCLUSION: Large benign schwannomas are rare. They
      need a tailored treatment, which in most cases works through one surgical
      approach. Usually it is possible to perform a complete resection with a good
      postoperative prognosis.

PMID- 25577453
TI  - The intra- and postoperative management of accidental durotomy in lumbar spine
      surgery: results of a German survey.
AB  - BACKGROUND: The intra- and postoperative management of accidental durotomy in
      operations of the lumbar spine is not standardized. It is the aim of our survey
      to obtain an overview on the current practice in neurosurgical departments in
      Germany. METHODS: The used questionnaire consisted of three questions and could
      be answered within a few minutes by checking boxes. In September 2012, the
      questionnaire was sent to 149 German neurosurgical departments. In the following
      4 weeks 109 replies (73.2 %) were received. RESULTS: Seventy-one neurosurgical
      departments (65.1 %) treat dural tears by a combination of methods, 28 (25.7 %)
      with suture alone, 7 (6.4 %) with fibrin-coated fleeces alone, 2 (1.8 %) with
      muscle patch alone and 1 (0.9 %) with fibrin glue alone. Sixty-six neurosurgical
      departments (60.5 %) decide on postoperative bed rest depending on the quality of
      the dural closure. Forty-three (39.5 %) neurosurgical departments do not rely on
      the quality of the dural closure for their postoperative management. In total,
      72.5 % of the neurosurgical departments prescribe bed rest for 1-3 days, 1.8 %
      for more than 3 days, whereas 25.7 % allow immediate mobilization. CONCLUSIONS:
      Among German neurosurgeons, no consensus exists concerning the intra- and
      postoperative management of accidental durotomies in lumbar spine surgery.
      Despite not being proved to reduce the rate of cerebrospinal fluid fistulas, bed
      rest is frequently used. As bed rest prolongs the hospital stay with additional
      costs and has the potential of a higher rate of medical complications, a
      prospective multicenter trial is warranted.

PMID- 25577454
TI  - Management of the primary intraosseous synovial sarcoma of the jaws: be careful
      of the surgical margin.
AB  - PURPOSE: Synovial sarcoma (SS) is extremely rare in the jaws, and only 8 cases
      have been reported worldwide. The specific aims of this study were to report 15
      cases of primary intraosseous SS (PISS) and analyze the histologic features and
      outcome-related prognostic factors. MATERIALS AND METHODS: Data from patients
      diagnosed with PISS from 2004 to 2013 were collected in this retrospective study.
      Patient characteristics (primary location, histologic subtype, tumor size, and
      surgical margin) were defined as predictor variables. Local recurrence and tumor
      related death were outcome variables. The association of tumor-related outcomes
      with patient characteristics was analyzed using Kaplan-Meier and Cox regression
      statistics. Other clinical and pathologic characteristics were summarized as a
      third category of variables for further analysis. RESULTS: This study examined 15
      cases (women, n = 10; men, n = 5) with a mean age at diagnosis of 35 years. There
      was no imbalance in the distribution of primary SS locations (maxilla, n = 7;
      mandible, n = 8). Six patients (40%) developed local recurrence and 4 patients
      (26.7%) had a tumor-related death. The 5-year local recurrence-free survival
      (LRFS) and overall survival rates were 57% and 69.1%, respectively. The strong
      statistical association of surgical margin with 5-year LRFS rate was shown by
      univariate (P = .01) and multivariate (hazard ratio = 7.598; P = .028) analyses.
      CONCLUSIONS: PISS is extremely rare in the jaw. Immunohistochemical analysis
      played an important role in the diagnosis of PISS. The surgical margin showed a
      strong association with local recurrence. Thus, ideal surgical margins should be
      achieved during surgery to obtain better local control.

PMID- 25577455
TI  - Chondrosarcoma of the temporomandibular disc: behavior over a 28-year observation
      period.
AB  - Chondrosarcoma of the head and neck occurs infrequently, with a recorded
      prevalence of only 5 to 12% of all such tumors; this in total represents only 17
      to 22% of all monostotic bone malignancies. Chondrosarcomas arising in the region
      of the temporomandibular joint are especially rare, with only 28-including
      subsets-recorded in the 6 decades since the first report in 1954. The lesion
      described in the present report would appear to be the first arising solely from
      the disc itself, and the postoperative period of observation is the longest on
      record. The patient's course over 27 years shows the need for ongoing vigilance
      in the management of this tumor.

PMID- 25577456
TI  - Local versus general anesthesia for the management of nasal bone fractures: a
      systematic review and meta-analysis.
AB  - PURPOSE: The aim of this study was to answer the following question: in patients
      with nasal bone fractures (NBFs), does closed reduction under local anesthesia
      (LA) produce comparable outcomes as closed reduction under general anesthesia
      (GA)? MATERIALS AND METHODS: A systematic review with meta-analysis and a
      comprehensive electronic search without date and language restrictions was
      performed in August 2014. The inclusion criteria were studies in humans,
      including randomized or quasi-randomized controlled trials (RCTs), controlled
      clinical trials (CCTs), and retrospective studies whose aim was comparing
      clinical outcomes between LA and GA for closed reduction of NBFs. RESULTS: Eight
      publications were included: 3 RCTs, 2 CCTs, and 3 retrospective studies. Three
      studies showed a low risk of bias, and 5 studies showed a moderate risk of bias.
      There was no statistical difference between LA and GA for closed reduction of
      NBFs with regard to patient satisfaction with anesthesia, patient satisfaction
      with function of the nose, need for subsequent retreatment (septoplasty,
      septorhinoplasty, or rhinoplasty with refracture), and a patient's chosen
      treatment for a refracture of the nose. There was a statistical difference
      between LA and GA for closed reduction of NBFs with regard to patient
      satisfaction with the appearance of the nose. CONCLUSION: Regardless of the cost
      and risks associated with GA, the results of the meta-analysis showed that GA
      provides better patient satisfaction with anesthesia, appearance and function of
      the nose, and preference of treatment for a refracture of the nose. In addition,
      the meta-analysis showed that GA decreased the number of subsequent corrective
      surgeries (septoplasty, septorhinoplasty, and rhinoplasty) required.

PMID- 25577457
TI  - Mesial inclination of impacted third molars and its propensity to stimulate
      external root resorption in second molars--a cone-beam computed tomographic
      evaluation.
AB  - PURPOSE: To investigate the presence of external root resorption (ERR) in second
      molars adjacent to horizontally and mesioangular impacted mandibular third molars
      by cone-beam computed tomography. In addition, patient characteristics (age and
      gender) and third molar depth were correlated with the presence of ERR. MATERIALS
      AND METHODS: The sample consisted of 116 scans (58 acquired on the i-CAT Classic
      and 58 on the Picasso-Trio) of 70 women and 46 men (mean age, 23.7 yr). Two
      observers recorded the presence of ERR in the second molars, inclination and
      depth of third molars in relation to bone and soft tissues, third molars
      classification according to Pell and Gregory, and location and severity of ERR.
      Data were analyzed by analysis of variance, Mann-Whitney test, and chi(2) test.
      The kappa test was used to analyze intraobserver agreement. RESULTS: The overall
      prevalence of ERR was 49.43%. There were no statistically significant differences
      in the detection of ERR by gender, images from the 2 devices, or third molar
      inclination (P > .05). The kappa test showed excellent reproducibility values
      (kappa = 0.7778). There was a smaller proportion of affected patients 14 to 24
      years old and ERR in teeth adjacent to Class C third molars. CONCLUSION: Mesially
      inclined third molars (mesioangular and horizontal) have a greater potential of
      being associated with ERR in second molars, which was shown by the high
      prevalence of the condition in the overall sample. Class A and B third molars in
      patients older than 24 years were more associated with the presence of ERR in
      adjacent teeth.

PMID- 25577458
TI  - Finite-element analysis of 3 situations of trauma in the human edentulous
      mandible.
AB  - PURPOSE: Maxillofacial trauma resulting from falls in elderly patients is a major
      social and health care concern. Most of these traumatic events involve mandibular
      fractures. The aim of this study was to analyze stress distributions from
      traumatic loads applied on the symphyseal, parasymphyseal, and mandibular body
      regions in the elderly edentulous mandible using finite-element analysis (FEA).
      MATERIALS AND METHODS: Computerized tomographic analysis of an edentulous
      macerated human mandible of a patient approximately 65 years old was performed.
      The bone structure was converted into a 3-dimensional stereolithographic model,
      which was used to construct the computer-aided design (CAD) geometry for FEA. The
      mechanical properties of cortical and cancellous bone were characterized as
      isotropic and elastic structures, respectively, in the CAD model. The condyles
      were constrained to prevent free movement in the x-, y-, and z-axes during
      simulation. This enabled the simulation to include the presence of masticatory
      muscles during trauma. Three different simulations were performed. Loads of 700 N
      were applied perpendicular to the surface of the cortical bone in the symphyseal,
      parasymphyseal, and mandibular body regions. The simulation results were
      evaluated according to equivalent von Mises stress distributions. RESULTS:
      Traumatic load at the symphyseal region generated low stress levels in the mental
      region and high stress levels in the mandibular neck. Traumatic load at the
      parasymphyseal region concentrated the resulting stress close to the mental
      foramen. Traumatic load in the mandibular body generated extensive stress in the
      mandibular body, angle, and ramus. CONCLUSIONS: FEA enabled precise mapping of
      the stress distribution in a human elderly edentulous mandible (neck and
      mandibular angle) in response to 3 different traumatic load conditions. This
      knowledge can help guide emergency responders as they evaluate patients after a
      traumatic event.

PMID- 25577459
TI  - Surgical treatment of adult mandibular condylar fractures provides better
      outcomes than closed treatment: a systematic review and meta-analysis.
AB  - PURPOSE: The purposes of this study were to identify significant differences in
      clinical outcomes between open reduction and rigid internal fixation (ORIF) and
      closed treatment (CT) for adult mandibular condylar fractures (MCFs) and to
      support or refute the superiority of one method over the other. MATERIALS AND
      METHODS: To address our purpose, we designed and implemented a systematic review
      with meta-analysis. A comprehensive electronic search without date and language
      restrictions was performed in May 2014. The inclusion criteria were studies in
      humans, including randomized or quasi-randomized controlled trials, controlled
      clinical trials, and retrospective studies, that compared ORIF and CT regarding
      maximal interincisal opening, laterotrusive and protrusive movements, pain,
      malocclusion, chin deviation on mouth opening, and temporomandibular joint signs
      or symptoms for the management of unilateral or bilateral adult MCFs. Meta
      analysis was conducted only if there were studies of similar comparisons
      reporting the same outcome measures. For binary outcomes, we calculated a
      standard estimation of the odds ratio by the random-effects model if
      heterogeneity was detected; otherwise, a fixed-effects model with a 95%
      confidence interval was performed. Weighted mean differences or standard mean
      differences were used to construct forest plots of continuous data. RESULTS:
      Twenty-three publications were included: 5 randomized controlled trials, 16
      controlled clinical trials, and 2 retrospective studies. Five studies showed a
      low risk of bias, whereas 18 showed a moderate risk of bias. There were
      statistically significant differences between ORIF and CT regarding maximal
      interincisal opening, laterotrusive movement, protrusive movement, malocclusion,
      pain, and chin deviation on mouth opening (P = .001, P = .001, P = .001, P =
      .001, P = .001, and P = .05, respectively). CONCLUSIONS: The result of the meta
      analysis confirmed that ORIF provides superior functional clinical outcomes
      (subjective and objective) compared with CT in the management of adult MCFs.

PMID- 25577460
TI  - Chronic osteomyelitis of the mandible: diagnosis and management--an institution's
      experience over 7 years.
AB  - PURPOSE: The objective of this study was to retrospectively evaluate and report
      the associated factors with the diagnosis and management of 24 patients with
      chronic osteomyelitis of the mandible seen at the authors' institution during the
      past several years. PATIENTS AND METHODS: Only cases of chronic osteomyelitis of
      the mandible not associated with antiresorptive medications or radiotherapy to
      the maxillofacial region were included in the study. After confirmation of the
      diagnosis, initial clinical and radiologic findings, treatment approach, and
      outcome were evaluated for each patient. Fourteen male and 10 female patients
      (average age, 53.75 yr; range, 22 to 83 yr) were included. RESULTS: The peak
      incidence of the disease was recorded in the fifth and sixth decades of life. An
      uneventful healing was observed in 20 patients (83.3%). One of 18 patients (5.5%)
      who underwent segmental resections developed a secondary infection and was
      managed with intravenously administered antibiotics. Three of 6 patients (50%)
      who were treated with marginal resections remained symptomatic after surgery.
      CONCLUSION: Independent of the cause and presentation of the disease, complete
      resolution of the infection should be the main focus of management in patients
      with chronic osteomyelitis of the mandible, and findings of this retrospective
      study indicate that a conservative surgical approach is more likely to result in
      a less than ideal outcome.

PMID- 25577461
TI  - Noninvasive embryo viability assessment by quantitation of human haptoglobin
      alpha-1 fragment in the in vitro fertilization culture medium: an additional tool
      to increase success rate.
AB  - OBJECTIVE: To find new candidate molecules to assess embryo viability in a
      noninvasive manner. DESIGN: Prospective, blinded study with randomized sample
      collection. SETTING: University research center. PATIENTS(S): Ninety embryos
      implanted in 53 randomly selected patients (mean +/- SD age, 32.3 +/- 5.1 years)
      were analyzed. INTERVENTION(S): Superovulation treatment was initiated by the
      administration of the GnRh agonist triptorelin and individual dosages of
      recombinant FSH. Ovulation was induced by the injection of hCG. Oocytes were
      fertilized by intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): Liquid
      chromatography coupled mass spectrometric quantification of the alpha-1 fragment
      of human haptoglobin in the culture medium. RESULT(S): A novel polypeptide marker
      was found that might be helpful to differentiate between potentially viable and
      nonviable embryos. This molecule was identified with tandem mass spectrometry as
      the alpha-1 fragment of human haptoglobin. Significant correlation was found in
      the amount of the peptide fragment and the outcome of pregnancy. In the culture
      media of embryos that were assigned in the biochemical assay as nonviable
      (according to the amount of the haptoglobin fragment), there were no pregnancies
      detected; this assay revealed a 100% successful selection of the nonviable
      embryos. In the group assigned as viable, the rate of pregnancy was 54.7%.
      CONCLUSION(S): Viability of the embryo during the IVF process is assessed by
      microscopic inspection, resulting in a pregnancy rate of 25%-30%. Detection and
      quantitation of the alpha-1 haptoglobin fragment of the culture medium proved to
      be a useful additional method for identifying nonviable embryos, increasing the
      success rate to 50%.

PMID- 25577462
TI  - Nonsense mutation of EMX2 is potential causative for uterus didelphysis: first
      molecular explanation for isolated incomplete mullerian fusion.
AB  - OBJECTIVE: To investigate the association between human empty spiracles homeobox
      2 gene (EMX2) and incomplete mullerian fusion (IMF). DESIGN: Case-control study.
      SETTING: University-based hospital. PATIENT(S): Cohort of 517 clinically well
      characterized IMF cases and 563 control women. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): In cases and control women, direct sequencing of EMX2 exons
      and further functional studies; for functional studies, wild-type and mutant EMX2
      expression plasmids constructed; human embryonic kidney cells (HEK293FT)
      transfected with empty vector, wild-type EMX2, mutant EMX2, and 1:1 combination
      (wild-type/mutant plasmids) with additional functional studies performed to
      clarify the deleterious effect of the novel mutation detected. RESULT(S): A novel
      nonsense mutation p.E142X was detected in one woman with a didelphic uterus (1 of
      517, 0.19%). The results of Western blot analysis confirmed that the mutation
      caused a truncated protein as predicted, and functional studies proved that it
      resulted in a dominant negative effect. CONCLUSION(S): The novel nonsense
      mutation we detected-EMX2, p.E142X- resulted in a dominant negative effect. The
      functional data were exemplified in HEK293FT cells. This reinforced the
      likelihood that EMX2 contributed to the pathophysiology of IMF. Although it is
      uncommon (0.19%), EMX2 is the first gene identified that if perturbed may cause
      isolated IMF.

PMID- 25577463
TI  - Ovulation rate and cycle characteristics in a subsequent clomiphene citrate cycle
      after stair-step protocol.
AB  - OBJECTIVE: To determine the ovulation rate after ovulation induction with
      clomiphene citrate (CC) in women who had previously been ovulatory after a stair
      step (CC-SS) ovulation induction. DESIGN: Retrospective cohort. SETTING:
      University-based tertiary fertility center. PATIENT(S): 61 anovulatory patients
      <40 years of age with polycystic ovary syndrome who underwent ovulation induction
      with a CC-SS protocol and a subsequent CC cycle. INTERVENTION(S): Ovulation
      induction with CC. MAIN OUTCOME MEASURE(S): Ovulation rates and cycle
      characteristics. RESULT(S): Of 61 patients who underwent a subsequent CC cycle,
      15 (25%) failed to ovulate at the previously ovulatory dose. Of those 15
      patients, 13 (86.7%) ovulated after an increase in dose. The total number of
      follicles >=15 mm (2.8 +/- 1.2 vs. 1.6 +/- 0.7) and peak estradiol (E2) levels
      (604 +/- 272 pg/mL vs. 447 +/- 218 pg/mL) were statistically significantly higher
      in the CC-SS cycle compared with the subsequent CC cycle, respectively. The
      endometrial lining was statistically significantly thinner in the CC-SS than the
      CC cycle (7.8 +/- 1.8 vs. 9.2 +/- 2.7, respectively). CONCLUSION(S): The majority
      of patients who ovulate after a CC-SS protocol will ovulate after taking the
      previously ovulatory CC dose in a subsequent cycle. Those who do not ovulate will
      likely ovulate with a further increase in CC dose.

PMID- 25577464
TI  - Second surgery for recurrent endometriomas is more harmful to healthy ovarian
      tissue and ovarian reserve than first surgery.
AB  - OBJECTIVE: To evaluate the excised specimen with histologic analysis and to
      assess the antral follicle count (AFC) at follow-up. This is to determine whether
      excisional surgery for recurrent endometriomas is more harmful to ovarian tissue
      and to the ovarian reserve than first surgery. DESIGN: Prospective controlled
      study. SETTING: University hospital. PATIENT(S): Consecutive patients with pelvic
      pain and/or infertility undergoing laparoscopic excision of a monolateral ovarian
      endometrioma for the first time (17 patients) or for recurrence after previous
      surgery (11 patients). INTERVENTION(S): Laparoscopic excision of ovarian
      endometrioma and ultrasonographic evaluation 3 months after surgery. MAIN OUTCOME
      MEASURE(S): Cyst wall histologic evaluation (specimen thickness, presence and
      morphology of ovarian tissue) and evaluation of ovarian reserve with AFC and
      ovarian volumes of both the operated and contralateral, nonoperated ovary at
      follow-up. RESULT(S): The cyst wall specimen was significantly thicker in the
      recurrent endometrioma group than in the first surgery group (1.7 +/- 0.3 mm vs.
      1.1 +/- 0.3 mm). Both main components of the cyst specimen (i.e., endometriosis
      tissue and ovarian tissue) were more represented in the recurrent endometrioma
      group than in the first surgery group. At sonographic follow-up, the operated
      ovary had a significantly lower AFC and volume than the contralateral nonoperated
      ovary in the recurrent endometrioma group, but not in the primary surgery group.
      CONCLUSION(S): Surgery for recurrent endometriomas is associated with evidence of
      a higher loss of ovarian tissue and is more harmful to the ovarian reserve
      evaluated by AFC and ovarian volume, if compared with endometriomas operated for
      the first time. Indications to surgery for recurrent endometriomas should be
      reconsidered with caution.

PMID- 25577465
TI  - Soy food intake and treatment outcomes of women undergoing assisted reproductive
      technology.
AB  - OBJECTIVE: To study the relation of dietary phytoestrogens intake and clinical
      outcomes of women undergoing infertility treatment with the use of assisted
      reproductive technology (ART). DESIGN: Prospective cohort study. SETTING:
      Fertility center. PATIENT(S): A total of 315 women who collectively underwent 520
      ART cycles from 2007 to 2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Implantation, clinical pregnancy, and live birth rates per initiated cycle.
      RESULT(S): Soy isoflavones intake was positively related to live birth rates in
      ART. Compared with women who did not consume soy isoflavones, the multivariable
      adjusted odds ratios of live birth (95% confidence interval) for women in
      increasing categories of soy isoflavones intake were 1.32 (0.76-2.27) for women
      consuming 0.54-2.63 mg/d, 1.87 (1.12-3.14) for women consuming 2.64-7.55 mg/d,
      and 1.77 (1.03-3.03) for women consuming 7.56-27.89 mg/d. CONCLUSION(S): Dietary
      soy intake was positively related to the probability of having a live birth
      during infertility treatment with ART.

PMID- 25577466
TI  - Association between ultrasound findings and serum levels of vascular endothelial
      growth factor in ampullary pregnancy.
AB  - OBJECTIVE: To assess the association between ultrasound images and serum
      concentrations of vascular endothelial growth factor (VEGF) in ampullary
      pregnancies. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S):
      Fifty patients with ampullary pregnancy. INTERVENTION(S): Criteria for inclusion
      in the study were: singleton pregnancy from spontaneous conception; diagnosis of
      tubal pregnancy in the ampullary region; radical surgical treatment
      (salpingectomy); and measurement of serum VEGF, human chorionic gonadotropin, and
      progesterone on the day of surgery. An additional criterion was description of an
      ectopic mass by transvaginal ultrasound, as follows: [1] ectopic gestational sac
      containing an embryo with cardiac activity; and [2] tubal ring: a paraovarian
      formation similar to a gestational sac, not containing a viable embryo (an
      anechoic structure surrounded by a peripheral hyperechogenic halo); an empty
      ectopic gestational sac; a sac containing an embryo without cardiac activity; or
      a vitelline vesicle. MAIN OUTCOME MEASURE(S): Association between ultrasound
      images and serum concentrations of VEGF. RESULT(S): An association was found
      between ultrasonographic images and VEGF serum concentrations. Ectopic embryos
      with cardiac activity were associated with higher levels of serum VEGF.
      CONCLUSION(S): In ampullary pregnancy, higher serum levels of VEGF are associated
      with the finding of an embryo with cardiac activity on transvaginal ultrasound.
      Greater production of VEGF likely creates development conditions more conducive
      to ectopic embryos.

PMID- 25577467
TI  - Saturated fat and cholesterol are critical to inducing murine metabolic syndrome
      with robust nonalcoholic steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the
      metabolic syndrome (MetS). Up to a third of NAFLD subjects are at risk for
      developing nonalcoholic steatohepatitis (NASH). Many rodent models fail to
      replicate both MetS and NASH. The purpose of this study was to develop a reliable
      mouse model of NASH and MetS using a diet containing cholesterol, saturated fat
      and carbohydrate that is reflective of Western diets of North Americans.
      EXPERIMENTAL DESIGN: We used adult male C57BL/6 J 4- to 5-week-old mice and
      administered a solid diet containing 0.2% cholesterol, 45% of its calories from
      fat, with 30% of the fat in the form of partially hydrogenated vegetable oil. We
      also provided carbohydrate largely as high-fructose corn syrup equivalent in
      water. In a separate cohort, we gave the identical diet in the absence of
      cholesterol. Glucose and insulin tolerance testing was conducted throughout the
      feeding period. The feeding was conducted for 16 weeks, and the mice were
      sacrificed for histological analysis, markers of MetS, liver inflammation,
      circulating lipids, as well as liver staining for fibrosis and alpha smooth
      muscle actin (alpha-SMA). RESULTS: We found that cholesterol significantly
      increased serum leptin, interleukin-6, liver weight and liver weight/body weight
      ratio, fibrosis and liver alpha-SMA. CONCLUSIONS: Mice administered a diet
      accurately reflecting patterns associated with humans afflicted with MetS can
      reliably replicate features of MetS, NASH and significant liver fibrosis. The
      model we describe significantly reduces the time by several months for
      development of stage 3 hepatic fibrosis.

PMID- 25577469
TI  - Minimum standards for the certification of patient decision support
      interventions: feasibility and application.
AB  - OBJECTIVE: Patient decision support interventions are not currently subject to
      standardized quality control. The current study aims to assess the feasibility of
      applying a proposed set of minimum standards (previously developed as part of a
      possible certification process) to a selection of existing patient decision
      support interventions. METHODS: A convenience sample of interventions selected
      from those included in the 2009 Cochrane systematic review of patient decision
      aids was scored by trained raters using the International Patient Decision Aids
      Standards (IPDAS) instrument. Scores were then evaluated against the published
      proposed minimum standards. RESULTS: Twenty-five out of thirty included
      interventions met all qualifying criteria while only three met the proposed
      certification criteria. The changes required for an intervention to meet the
      proposed certification standards were relatively minor. There was considerable
      variation between raters' mean scores. CONCLUSIONS: Most interventions did not
      meet the certification criteria due to lack of information on modifiable items
      such as update policy and funding source. PRACTICE IMPLICATIONS: Specifying
      minimum standards for patient decision support interventions is a feasible
      development. However, it remains unclear whether the minimum standards can be
      applied to interventions designed for use within clinical encounters and to those
      that target screening and diagnostic tests.

PMID- 25577470
TI  - Disease-related knowledge in cardiac rehabilitation enrollees: correlates and
      changes.
AB  - OBJECTIVES: To describe (1) patients' disease-related knowledge at cardiac
      rehabilitation (CR) entry; (2) correlates of this knowledge; (3) whether CR
      completion is related to knowledge; and (4) behavioral correlates of knowledge.
      METHODS: For this prospective, observational study, a convenience sample of new
      CR patients was approached at 3 programs to complete a survey. It consisted of
      sociodemographic items, heart-health behavior surveys, and the CADE-Q. Patients
      were provided a similar survey 6 months later. RESULTS: 214 patients completed
      the CADE-Q at both points, with scores demonstrating "acceptable" to "good"
      knowledge. Higher knowledge at CR entry was significantly associated with greater
      education, being married, greater English-language proficiency, and history of
      percutaneous coronary intervention (p<=0.05). The 118 (55.1%) patients that
      completed CR demonstrated significantly higher knowledge than non-enrollees at
      post-test (p<=0.05). There was a significant positive association between
      knowledge and physical activity (p<=0.01) and nutrition (p<=0.05) at post-test,
      but no association with smoking or medication adherence. CONCLUSIONS: CR
      adherence ensures patients sustain knowledge needed to optimize their disease
      management, and perhaps ultimately their health outcomes. PRACTICE IMPLICATIONS:
      CR completion should be promoted so patients remain educated about their disease
      management, and the health behaviors observed will be practiced in a greater
      proportion of patients.

PMID- 25577468
TI  - Luteolin protects against vascular inflammation in mice and TNF-alpha-induced
      monocyte adhesion to endothelial cells via suppressing IKappaBalpha/NF-kappaB
      signaling pathway.
AB  - Vascular inflammation plays a significant role in the pathogenesis of
      atherosclerosis. Luteolin, a naturally occurring flavonoid present in many
      medicinal plants and some commonly consumed fruits and vegetables, has received
      wide attention for its potential to improve vascular function in vitro. However,
      its effect in vivo and the molecular mechanism of luteolin at physiological
      concentrations remain unclear. Here, we report that luteolin as low as 0.5 MUM
      significantly inhibited tumor necrosis factor (TNF)-alpha-induced adhesion of
      monocytes to human EA.hy 926 endothelial cells, a key event in triggering
      vascular inflammation. Luteolin potently suppressed TNF-alpha-induced expression
      of the chemokine monocyte chemotactic protein-1 (MCP-1) and adhesion molecules
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1), key mediators involved in enhancing endothelial cell-monocyte
      interaction. Furthermore, luteolin inhibited TNF-alpha-induced nuclear factor
      (NF)-kappaB transcriptional activity, IkappaBalpha degradation, expression of
      IkappaB kinase beta and subsequent NF-kappaB p65 nuclear translocation in
      endothelial cells, suggesting that luteolin can inhibit inflammation by
      suppressing NF-kappaB signaling. In an animal study, C57BL/6 mice were fed a diet
      containing 0% or 0.6% luteolin for 3 weeks, and luteolin supplementation greatly
      suppressed TNF-alpha-induced increase in circulating levels of MCP-1/JE, CXCL1/KC
      and sICAM-1 in C57BL/6 mice. Consistently, dietary intake of luteolin
      significantly reduced TNF-alpha-stimulated adhesion of monocytes to aortic
      endothelial cells ex vivo. Histology shows that luteolin treatment prevented the
      eruption of endothelial lining in the intima layer of the aorta and preserved
      elastin fibers' delicate organization as shown by Verhoeff-Van Gieson staining.
      Immunohistochemistry studies further show that luteolin treatment also reduced
      VCAM-1 and monocyte-derived F4/80-positive macrophages in the aorta of TNF-alpha
      treated mice. In conclusion, luteolin protects against TNF-alpha-induced vascular
      inflammation in both in vitro and in vivo models. This anti-inflammatory effect
      of luteolin may be mediated via inhibition of the NF-kappaB-mediated pathway.

PMID- 25577471
TI  - Diabetes risk reduction in overweight first degree relatives of type 2 diabetes
      patients: effects of a low-intensive lifestyle education program (DiAlert) A
      randomized controlled trial.
AB  - OBJECTIVES: To test the efficacy of a low-intensive lifestyle education program
      (DiAlert) for overweight first degree relatives of type 2 diabetes patients aimed
      at reducing diabetes risk. METHODS: Overweight first degree relatives of type 2
      diabetes patients were randomly assigned to the DiAlert intervention (N=45) or
      control group who received leaflets (N=51). DiAlert consists of two group
      sessions and newsletters. Assessments were scheduled at baseline, three and nine
      months, with weight loss as primary outcome. Secondary outcomes included
      anthropometric, metabolic, behavioral and psychological measures. Comparisons
      were made over time and between groups. RESULTS: Both groups showed modest weight
      loss with no difference between randomization groups. However, after DiAlert
      significantly more participants lost 5% of their weight compared to controls
      (P=0.03). Significant improvement of waist circumference sustained after 9 months
      in the intervention group (intervention: -4.33cm, P<0.01/control: -1.25cm,
      P=0.08). Systolic blood pressure improved within the intervention group
      (intervention: -8.77mmHg, P<0.01/control: -1.03mmHg, P=0.60). No effect was
      observed for biomedical and psychosocial outcomes. CONCLUSIONS: Our low-intensive
      structured lifestyle education program helps overweight relatives to improve
      waist circumference and supports relevant weight loss. PRACTICE IMPLICATIONS: The
      family approach provides opportunities to reach and engage relatives at risk in
      diabetes prevention education.

PMID- 25577472
TI  - A drifter for measuring water turbidity in rivers and coastal oceans.
AB  - A disposable instrument for measuring water turbidity in rivers and coastal
      oceans is described. It transmits turbidity measurements and position data via a
      satellite uplink to a processing server. The primary purpose of the instrument is
      to help document changes in sediment runoff from river catchments in North
      Queensland, Australia. The 'river drifter' is released into a flooded river and
      drifts downstream to the ocean, measuring turbidity at regular intervals.
      Deployment in the Herbert River showed a downstream increase in turbidity, and
      thus suspended sediment concentration, while for the Johnstone River there was a
      rapid reduction in turbidity where the river entered the sea. Potential stranding
      along river banks is a limitation of the instrument. However, it has proved
      possible for drifters to routinely collect data along 80 km of the Herbert River.
      One drifter deployed in the Fly River, Papua New Guinea, travelled almost 200 km
      before stranding.

PMID- 25577473
TI  - Sharks and people: insight into the global practices of tourism operators and
      their attitudes to shark behaviour.
AB  - Shark tourism is a popular but controversial activity. We obtained insights into
      this industry via a global e-mailed questionnaire completed by 45
      diving/snorkelling operators who advertised shark experiences (shark operators)
      and 49 who did not (non-shark operators). 42% of shark operators used an
      attractant to lure sharks and 93% stated they had a formal code of conduct which
      86% enforced "very strictly". While sharks were reported to normally ignore
      people, 9 operators had experienced troublesome behaviour from them. Whilst our
      research corroborates previous studies indicating minimal risk to humans from
      most shark encounters, a precautionary approach to provisioning is required to
      avoid potential ecological and societal effects of shark tourism. Codes of
      conduct should always stipulate acceptable diver behaviour and appropriate diver
      numbers and shark operators should have a moral responsibility to educate their
      customers about the need for shark conservation. 

PMID- 25577474
TI  - Assessing the water quality response to an alternative sewage disposal strategy
      at bathing sites on the east coast of Ireland.
AB  - A three-dimensional model is used to assess the bathing water quality of Bray and
      Killiney bathing sites in Ireland following changes to the sewage management
      system. The model, firstly calibrated to hydrodynamic and water quality data from
      the period prior to the upgrade of the Wastewater Treatment Works (WwTW), was
      then used to simulate Escherichia coli (E. coli) distributions for discharge
      scenarios of the periods prior to and following the upgrade of the WwTW under dry
      and wet weather conditions. E. coli distributions under dry weather conditions
      demonstrate that the upgrade in the WwTW has remarkably improved the bathing
      water quality to a Blue Flag status. The new discharge strategy is expected to
      drastically reduce the rainfall-related incidents in which environmental limits
      of the Bathing Water Directive are breached. However, exceedances to these limits
      may still occur under wet weather conditions at Bray bathing site due to storm
      overflows that may still be discharged through two sea outfalls offshore of Bray
      bathing site. 

PMID- 25577475
TI  - Evaluation of beach cleanup effects using linear system analysis.
AB  - We established a method for evaluating beach cleanup effects (BCEs) based on a
      linear system analysis, and investigated factors determining BCEs. Here we focus
      on two BCEs: decreasing the total mass of toxic metals that could leach into a
      beach from marine plastics and preventing the fragmentation of marine plastics on
      the beach. Both BCEs depend strongly on the average residence time of marine
      plastics on the beach (tau(r)) and the period of temporal variability of the
      input flux of marine plastics (T). Cleanups on the beach where tau(r) is longer
      than T are more effective than those where tau(r) is shorter than T. In addition,
      both BCEs are the highest near the time when the remnants of plastics reach the
      local maximum (peak time). Therefore, it is crucial to understand the following
      three factors for effective cleanups: the average residence time, the plastic
      input period and the peak time.

PMID- 25577476
TI  - Mediterranean fouling communities assimilate the organic matter derived from
      coastal fish farms as a new trophic resource.
AB  - Currently, the lipid content of fish feeds includes high amounts of terrestrial
      vegetable oils, rich in n-6 fatty acids and poor in n-3 fatty acids. Sinking
      organic matter in the shape of fragmented pellets and fish faeces could be
      ingested by the surrounding fauna attracted to the submerged structures of
      aquaculture facilities or living in natural benthic habitats. Fatty acids
      contained in feed pellets were used as trophic markers to shed light on the
      assimilation and incorporation of aquaculture wastes by the invertebrate fauna
      associated to sea-cages. Eighteen macroinvertebrate species, and zooplankton,
      seaweeds and sediments were collected from two fish farms, one of which (control)
      had not been used as such for two years. This study demonstrates that
      macroinvertebrate fauna present in fouling can take up sinking organic matter
      from farms. Further research should be directed at assessing the potential
      implications of aquaculture production for the surrounding ecosystem. 

PMID- 25577477
TI  - What adolescents enrolled in genomic addiction research want to know about
      conflicts of interest.
AB  - BACKGROUND: Perspectives of adolescent research participants regarding conflicts
      of interest (COIs) and their impact on trust in researchers have not been
      studied. This study evaluates views of adolescent patients in treatment for
      substance and conduct problems compared to controls enrolled in genomic addiction
      research. METHODS: Participants included 273 (190 patients, 83 controls)
      adolescents. Participants consented or assented (with parental consent) to have
      their genomic information deposited in a NIH biobank that shares information
      globally with qualified investigators. As part of that study, participants
      completed a COI survey. Endorsement of each COI item was analyzed with multiple
      logistic regressions, evaluating group, age, sex, ethnicity, and highest grade
      completed. RESULTS: Patients and controls differed in gender, ethnicity and
      highest grade completed. In response to the survey, 38.4% of patients and 25.3%
      of controls "want to know" and 35.3% of patients and 37.3% of controls "might
      want to know" about COIs. Males were less likely to want/might want disclosure
      about COIs. Older patients were more likely to want disclosure about financial
      interests; patients were more likely to want disclosure about possible
      treatments; males were more likely to want information about monetary gains. Both
      groups requested between 1 paragraph and 1 page of information. Disclosure of
      COIs did not impact trust for most participants. CONCLUSION: Adolescent patients
      and controls in this study want comparable information for disclosure of COIs
      including monetary gains, salary, publications, grants, and professional awards.
      Notably, the majority of patients and controls report that disclosure will not
      undermine trust in researchers.

PMID- 25577479
TI  - Why we need more ecology for genetic models such as C. elegans.
AB  - Functional information about the large majority of the genes is still lacking in
      the classical eukaryotic model species Drosophila melanogaster, Caenorhabditis
      elegans, and Mus musculus. Because many of these genes are likely to be important
      in natural settings, considering explicit ecological information should increase
      our knowledge of gene function. Using C. elegans as an example, we discuss the
      importance of biotic factors as a driving force in shaping the composition and
      structure of the nematode genome. We highlight examples for which consideration
      of ecological information and natural variation have been key to the
      identification of novel, unexpected gene functions, and use these examples to
      define future research avenues for the classical genetic model taxa. 

PMID- 25577478
TI  - Young adult cannabis users report greater propensity for risk-taking only in non
      monetary domains.
AB  - BACKGROUND: Though substance use is often associated with elevated risk-taking in
      real-world scenarios, many risk-taking tasks in experimental psychology using
      financial gambles fail to find significant differences between individuals with
      substance use disorders and healthy controls. We assessed whether participants
      using marijuana would show a greater propensity for risk-taking in distinct
      domains including, but not limited to, financial risk-taking. METHODS: In the
      current study, we assessed risk-taking in young adult (age 18-25) regular
      marijuana users and in non-using control participants using a domain-specific
      risk-taking self-report scale (DOSPERT) encompassing five domains of risk-taking
      (social, financial, recreational, health/safety, and ethical). We also measured
      behavioral risk-taking using a laboratory monetary risk-taking task. RESULTS:
      Marijuana users and controls reported significant differences on the social,
      health/safety, and ethical risk-taking scales, but no differences in the
      propensity to take recreational or financial risks. Complementing the self-report
      finding, there were no differences between marijuana users and controls in their
      performance on the laboratory risk-taking task. CONCLUSIONS: These findings
      suggest that financial risk-taking may be less sensitive than other domains of
      risk-taking in assessing differences in risky behavior between those who use
      marijuana and those who do not. In order to more consistently determine whether
      increased risk-taking is a factor in substance use, it may be necessary to use
      both monetary risk-taking tasks and complementary assessments of non-monetary
      based risk-taking measures.

PMID- 25577480
TI  - [Comorbidity -- mind and body interconnection based on the new findings].
AB  - Comorbidity is a multicausal, multidimensional, multifaced phenomenon in
      medicine. There are many different definitions of the co-occurrence of two or
      more disorders, but Feinstein's is the most acceptable. Although epidemiological
      data show a high prevalence of comorbidity of somatic and psychiatric disorders,
      it is still underrecognized and undertreated. There are many unanswered questions
      related to comorbidity, including whether comorbidity is a valid phenomenon;
      whether the epidemiological results have validity; what is the linkage between
      somatic and psychological processes; which factors take part in the bidirectional
      manifestation; how do we treat the involved disorders; what is the right
      organization to manage the patients. The aim of the author was to review
      different aspects of comorbidity with the help of new knowledge. The starting
      point of the interpretation was the concept of identical biological substrates
      (pathophysiological endpoint) that generate the development of somatic and
      psychiatric disorders. The formation of these substrates is influenced by risk
      factors, which depend or not on the person (stressors vs genes). The effects of
      risk factors and biological substrates are parallel to each other, but one of
      them is a dominant agent. The author's concept ("dominance theory") is based on
      new discoveries of the biological mechanisms of psychiatric processes to help to
      understand the phenomenon of comorbidity and develop new therapies. It is very
      important to recognize, to diagnose and treat comorbidity because of the
      prevalence of excess mortality is high and the morbidity burden influences the
      patient' quality of life.

PMID- 25577481
TI  - [Psychiatric aspects of infectious diseases -- a literature review].
AB  - It is essential for the psychiatrist working in the consultation-liaison field or
      with comorbid patients to be familiar with the psychiatric aspects of central
      nervous infectious diseases or infectious diseases with psychiatric symptoms.
      Authors have reviewed the most important psychiatric aspects of common infectious
      diseases. Essential knowledge for setting up a diagnosis and starting appropriate
      treatment has been summarized. The most important interactions of infectological
      and psychiatric treatments have also been discussed. 

PMID- 25577482
TI  - Catatonia in DSM 5: controversies regarding its psychopathology, clinical
      presentation and treatment response.
AB  - Over the past two decades, there has been an upsurge of interest in catatonia,
      which is reflected in the attention it received in DSM 5, where it appears as a
      separate subsection of the Schizophrenia Spectrum and Other Psychotic Disorders
      (APA, 2013). This commentary argues that due to the lack of solid scientific
      evidence, the extended coverage of catatonia in DSM 5 was a premature, and
      consequently, a necessarily ambiguous decision. The psychopathological
      foundations of the modern catatonia concept are lacking therefore its boundaries
      are fuzzy. There are only a few, methodologically sound clinical, treatment
      response and small-scale neurobiological studies. The widely recommended use of
      benzodiazepines for the treatment of catatonia is based on case reports and open
      label studies instead of placebo-controlled, randomized trials. In conclusion,
      the catatonic concept espoused by DSM 5 is necessarily vague reflecting the
      current state of knowledge. 

PMID- 25577483
TI  - [Correlation between treatment of depression and suicide mortality in Hungary --
      focus on the effects of the 2007 healthcare reform].
AB  - Major depression is a common but still underdiagnosed and undertreated illness
      which, with its complications (suicide, secondary alcoholism, loss of
      productivity, increased cardiovascular morbidity and mortality), is a major
      public health problem worldwide. Implementing the present pharmacological and non
      pharmacological treatment strategies, major depression can be successfully
      treated resulting in a significant decline in suicide risk and the economic
      burden caused by untreated depression is much higher than the cost of treatment.
      In the present paper the authors also discuss the impact of the development of
      the Hungarian psychiatric care system in the past three decades and the 2008
      recession on the changing national suicide rate. Like international data,
      Hungarian studies also show that more widespread and effective treatment of
      depression is the main component of the more than 50-percent decline of suicide
      mortality in Hungary during the last 30 years. 

PMID- 25577485
TI  - Ozone effects on wheat grain quality - a summary.
AB  - We synthesized the effects of ozone on wheat quality based on 42 experiments
      performed in Asia, Europe and North America. Data were analysed using meta
      analysis and by deriving response functions between observed effects and daytime
      ozone concentration. There was a strong negative effect on 1000-grain weight and
      weaker but significant negative effects on starch concentration and volume
      weight. For protein and several nutritionally important minerals (K, Mg, Ca, P,
      Zn, Mn, Cu) concentration was significantly increased, but yields were
      significantly decreased by ozone. For other minerals (Fe, S, Na) effects were not
      significant or results inconclusive. The concentration and yield of potentially
      toxic Cd were negatively affected by ozone. Some baking properties (Zeleny value,
      Hagberg falling number) were positively influenced by ozone. Effects were similar
      in different exposure systems and for spring and winter wheat. Ozone effects on
      quality should be considered in future assessments of food security/safety. 

PMID- 25577484
TI  - [Movement disorders is psychiatric diseases].
AB  - Movement disorders are common in psychiatry. The movement disorder can either be
      the symptom of a psychiatric disorder, can share a common aetiological factor
      with it, or can be the consequence of psychopharmacological therapy. Most common
      features include tic, stereotypy, compulsion, akathisia, dyskinesias, tremor,
      hypokinesia and disturbances of posture and gait. We discuss characteristics and
      clinical importance of these features. Movement disorders are frequently present
      in mood disorders, anxiety disorders, schizophrenia, catatonia, Tourette-disorder
      and psychogenic movement disorder, leading to differential-diagnostic and
      therapeutical difficulties in everyday practice. Movement disorders due to
      psychopharmacotherapy can be classified as early-onset, late-onset and tardive.
      Frequent psychiatric comorbidity is found in primary movement disorders, such as
      Parkinson's disease, Wilson's disease, Huntington's disease, diffuse Lewy-body
      disorder. Complex neuropsychiatric approach is effective concerning overlapping
      clinical features and spectrums of disorders in terms of movement disorders and
      psychiatric diseases.

PMID- 25577486
TI  - [Efficacy and safety of intra- and periarticular corticosteroid injections in
      treatment of lupus arthritis].

PMID- 25577488
TI  - ?
AB  - Hypertrophic osteoarthropathy (HOA) is a condition characterized by
      arthralgia/arthritis, clubbing, and periosteal reaction. Primary form of HOA is
      observed at early ages of life and is hereditary in nature. Secondary HOA is more
      frequently seen in clinical setting and occurs as a result of various disorders
      including inflammatory and malignant diseases. Regression in HOA may be seen
      after the treatment of underlying condition. In this report, we presented a case
      of HOA coexisted with myelofibrosis and reviewed the current literature.

PMID- 25577489
TI  - The role of crossmodal competition and dimensional overlap in crossmodal
      attention switching.
AB  - Crossmodal selective attention was investigated in a cued task switching paradigm
      using bimodal visual and auditory stimulation. A cue indicated the imperative
      modality. Three levels of spatial S-R associations were established following
      perceptual (location), structural (numerical), and conceptual (verbal) set-level
      compatibility. In Experiment 1, participants switched attention between the
      auditory and visual modality either with a spatial-location or spatial-numerical
      stimulus set. In the spatial-location set, participants performed a localization
      judgment on left vs. right presented stimuli, whereas the spatial-numerical set
      required a magnitude judgment about a visually or auditorily presented number
      word. Single-modality blocks with unimodal stimuli were included as a control
      condition. In Experiment 2, the spatial-numerical stimulus set was replaced by a
      spatial-verbal stimulus set using direction words (e.g., "left"). RT data showed
      modality switch costs, which were asymmetric across modalities in the spatial
      numerical and spatial-verbal stimulus set (i.e., larger for auditory than for
      visual stimuli), and congruency effects, which were asymmetric primarily in the
      spatial-location stimulus set (i.e., larger for auditory than for visual
      stimuli). This pattern of effects suggests task-dependent visual dominance. 

PMID- 25577487
TI  - Pregnancy outcomes in dermatomyositis and polymyositis patients.
AB  - BACKGROUND: Currently, there are few studies that describe pregnancy in
      dermatomyositis/polymyositis patients, and they are largely limited to case
      reports or studies with few samples. OBJECTIVES: Therefore, we describe the
      pregnancy in a large sample of patients with dermatomyositis/polymyositis and to
      analyze the outcomes in those who became pregnant during or after disease onset.
      METHODS: The present single-center study analyzed 98 female patients with
      idiopathic inflammatory myopathies (60 dermatomyositis and 38 polymyositis
      patients). They were interviewed to obtain obstetric antecedent and demographic
      data from June 2011 to June 2012. RESULTS: Seventy-eight (79.6%) of the 98
      patients had obstetric histories. Six polymyositis and 9 dermatomyositis patients
      became pregnant after disease onset. The pregnancy outcomes in these cases were
      good, except in the following cases: 1 disease reactivation, 1 intrauterine
      growth retardation, 1 diabetes mellitus, 1 hypertension, 1 hypothyroidism, and 2
      fetal losses (same patient). Moreover, 2 patients developed dermatomyositis
      during pregnancy and 4 (2 polymyositis and 2 dermatomyositis) during the
      postpartum period with good control after glucocorticoid and immunosuppressant
      therapy. CONCLUSIONS: The adverse obstetric events were related to clinical
      intercurrences and the pregnancy does not seem to carry a worse prognosis
      specifically in disease (for example: disease relapsing). Moreover,
      dermatomyositis or polymyositis onset during pregnancy or the postpartum period
      had good outcome after drug therapy.

PMID- 25577490
TI  - Summarizing slant perception with words and hands; an empirical alternative to
      correlations in Shaffer, McManama, Swank, Williams & Durgin (2014).
AB  - The paper by Shaffer, McManama, Swank, Williams & Durgin (2014) uses correlations
      between palm-board and verbal estimates of geographical slant to argue against
      dissociation of the two measures. This paper reports the correlations between the
      verbal, visual and palm-board measures of geographical slant used by Proffitt and
      co-workers as a counterpoint to the analyses presented by Shaffer and colleagues.
      The data are for slant perception of staircases in a station (N=269), a shopping
      mall (N=229) and a civic square (N=109). In all three studies, modest
      correlations between the palm-board matches and the verbal reports were obtained.
      Multiple-regression analyses of potential contributors to verbal reports,
      however, indicated no unique association between verbal and palm-board measures.
      Data from three further studies (combined N=528) also show no evidence of any
      relationship. Shared method variance between visual and palm-board matches could
      account for the modest association between palm-boards and verbal reports. 

PMID- 25577491
TI  - Simultaneous interpretation selectively influences working memory and attentional
      networks.
AB  - Recent research has shown that becoming an expert in a certain domain may lead to
      a transfer of the acquired skills to other domains requiring similar abilities.
      Thus, the cognitive skills acquired by professional interpreters after intensive
      training may also transfer to other domains. Simultaneous interpreters are known
      to develop high working memory capacity (e.g., Christoffels, de Groot, & Kroll,
      2006; Signorelli, Haarmann, & Obler, 2012). However, little is known about
      transfer of other processes such us updating and some aspects of attention also
      involved in interpretation. In Experiment 1, we found that interpreters
      outperformed a control group in updating skills, as measured through a dual
      version of the n-back task (Jaeggi et al., 2007). In Experiment 2, use of the
      ANTI-V allowed us to reveal that interpreting differentially modulates the
      interactions between attentional networks. Thus, we found no group differences in
      conflict resolution, but the interaction between the alertness and orienting
      networks differed between interpreters and non-interpreters. Taken together,
      these results suggest that experience in simultaneous interpreting transfers to
      other domains, but this transfer seems specific to the cognitive processes more
      closely involved in the interpreting tasks. 

PMID- 25577492
TI  - Immobilization of selenite in soil and groundwater using stabilized Fe-Mn binary
      oxide nanoparticles.
AB  - Stabilized Fe-Mn binary oxide nanoparticles were synthesized and tested for
      removal and in-situ immobilization of Se(IV) in groundwater and soil. A water
      soluble starch or food-grade carboxymethyl cellulose (CMC) was used as a
      stabilizer to facilitate in-situ delivery of the particles into contaminated
      soil. While bare and stabilized nanoparticles showed rapid sorption kinetics,
      starch-stabilized Fe-Mn offered the greatest capacity for Se(IV). The Langmuir
      maximum capacity was determined to be 109 and 95 mg-Se/g-Fe for starch- and CMC
      stabilized nanoparticles, respectively, and the high Se(IV) uptake was observed
      over the typical groundwater pH range of 5-8. Column breakthrough tests indicated
      that the stabilized nanoparticles were deliverable in a model sandy soil while
      non-stabilized particles were not. When a Se(IV)-spiked soil was treated in situ
      with the nanoparticles, >90% water leachable Se(IV) was transferred to the
      nanoparticle phase, and thereby immobilized as the particles were retained in the
      downstream soil matrix. The nanoparticle amendment reduced the TCLP (toxicity
      characteristic leaching procedure) leachability and the California WET (waste
      extraction test) leachability of Se(IV) by 76% and 71%, respectively. The
      technology holds the potential to fill a major technology gap in remediation of
      metals-contaminated soil and groundwater.

PMID- 25577494
TI  - Interplay of glia activation and oxidative stress formation in fluoride and
      aluminium exposure.
AB  - BACKGROUND: Oxidative stress formation is pivotal in the action of environmental
      agents which trigger the activation of glial cells and neuroinflammation to
      stimulate compensatory mechanisms aimed at restoring homeostasis. AIM: This study
      sets to demonstrate the interplay of fluoride (F) and aluminium (Al) in brain
      metabolism. Specifically, it reveals how oxidative stress impacts the activation
      of astrocytes (GFAP), mediates proinflammatory responses (microglia and B-cells:
      CD68 and CD 20 respectively) and shows the pattern of lipid peroxidation in the
      brain following fluoride and (or) aluminium treatment in vivo. METHOD: Male adult
      Wistar rats were treated with low and high doses of fluoride, aluminium or
      combination of fluoride-aluminium for 30 days. The control group received
      distilled water for the duration of the treatment. Blood and brain tissue
      homogenates were prepared for colorimetric assay of stress biomarkers
      [malonialdehyde (MDA) and superoxide dismutase (SOD)]. Subsequent analysis
      involved immunodetection of astrocytes (anti-GFAP), microglial (anti-CD68) and B
      cells (anti-CD20) in coronal sections of the prefrontal cortex using antigen
      retrieval immunohistochemistry. RESULT AND CONCLUSION: Aluminium, fluoride and a
      combination of aluminium-fluoride treatments caused an increase in brain lipid
      peroxidation products and reactive oxygen species (ROS) formation. Similarly, an
      increase in glial activation and inflammatory response were seen in these groups
      versus the control. Oxidative stress induced glial activation (GFAP) and
      increased the expression of B cells (CD20). This also corresponded to the extent
      of tissue damage and lipid peroxidation observed. Taken together, the results
      suggest a close link between oxidative stress neuroinflamation and degeneration
      in aluminium-fluoride toxicity.

PMID- 25577493
TI  - Aldo-keto Reductase 1B15 (AKR1B15): a mitochondrial human aldo-keto reductase
      with activity toward steroids and 3-keto-acyl-CoA conjugates.
AB  - Aldo-keto reductases (AKRs) comprise a superfamily of proteins involved in the
      reduction and oxidation of biogenic and xenobiotic carbonyls. In humans, at least
      15 AKR superfamily members have been identified so far. One of these is a newly
      identified gene locus, AKR1B15, which clusters on chromosome 7 with the other
      human AKR1B subfamily members (i.e. AKR1B1 and AKR1B10). We show that alternative
      splicing of the AKR1B15 gene transcript gives rise to two protein isoforms with
      different N termini: AKR1B15.1 is a 316-amino acid protein with 91% amino acid
      identity to AKR1B10; AKR1B15.2 has a prolonged N terminus and consists of 344
      amino acid residues. The two gene products differ in their expression level,
      subcellular localization, and activity. In contrast with other AKR enzymes, which
      are mostly cytosolic, AKR1B15.1 co-localizes with the mitochondria. Kinetic
      studies show that AKR1B15.1 is predominantly a reductive enzyme that catalyzes
      the reduction of androgens and estrogens with high positional selectivity (17beta
      hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoA conjugates and
      exhibits strong cofactor selectivity toward NADP(H). In accordance with its
      substrate spectrum, the enzyme is expressed at the highest levels in steroid
      sensitive tissues, namely placenta, testis, and adipose tissue. Placental and
      adipose expression could be reproduced in the BeWo and SGBS cell lines,
      respectively. In contrast, AKR1B15.2 localizes to the cytosol and displays no
      enzymatic activity with the substrates tested. Collectively, these results
      demonstrate the existence of a novel catalytically active AKR, which is
      associated with mitochondria and expressed mainly in steroid-sensitive tissues. 

PMID- 25577495
TI  - Assessment of adherence with oral anticancer agents in oncology clinical trials:
      A systematic review.
AB  - BACKGROUND: Despite recommendations for adherence reporting in clinical trials
      involving an oral anticancer agent, the frequency and methods of adherence
      reporting are inconsistent. The purpose of this systematic review is to determine
      the frequency and type of adherence measures used in oncology and hematology
      clinical trials of oral anticancer agents and their association with study
      characteristics including quality, cancer type, stage and treatment type. DESIGN:
      PubMed was searched of all randomized controlled clinical trials assessing self
      administered pharmacological interventions in patients with cancer and published
      over two years, between 1 January 2011 and 31 December 2012 were evaluated.
      RESULTS: We identified 70 publications in the PubMed database, comprising 45,118
      total patients. Adherence reporting was present in 14 of 70 trials (20%);
      quantitative reporting was present in three of 70 trials (4%). Method of
      adherence assessment varied and included medication count, medication diaries and
      patient self-report. There was no association between adherence reporting and
      study quality or other study characteristics, although there was a trend towards
      increased reporting in breast cancer studies, with 46% of the studies reporting
      adherence (p = 0.0621). In a preliminary analysis, hematology studies (mean Jadad
      score 2.19 +/- 1.47) were found to have significantly lower quality when compared
      to non-hematology trials (mean Jadad score 3.39 +/- 1.37, p = 0.0034).
      CONCLUSION: This systematic review demonstrates adherence reporting in clinical
      trials of oral anticancer agents is infrequent. When reported, adherence was not
      associated with overall study quality or other study characteristics. Given the
      potential effects of non-adherence on study power and validity, adherence
      reporting should be encouraged in oncology and hematology clinical trials.

PMID- 25577496
TI  - Maternal mindfulness during pregnancy and infant socio-emotional development and
      temperament: the mediating role of maternal anxiety.
AB  - BACKGROUND: Accumulating evidence shows that maternal anxiety during pregnancy
      adversely affects child outcomes. The positive effects of maternal psychosocial
      factors during pregnancy on child outcomes are not yet studied. This prospective
      study addresses the association between maternal mindfulness during pregnancy and
      socio-emotional development and temperament in 10months-old infants. We also
      investigated whether this association was mediated by maternal anxiety. METHOD:
      Mothers (N=90) provided information about mindfulness and anxiety at the
      beginning of the second trimester of pregnancy. Infant socio-emotional
      development (Ages and Stages Questionnaire: Social Emotional; ASQ:SE) and
      temperament (Infant Behaviour Questionnaire-Revised; IBQ-R) were assessed at age
      10months. RESULTS: Higher maternal mindfulness during pregnancy was associated
      with less infant self-regulation problems and less infant negative affectivity.
      Mediation analysis showed that maternal anxiety mediated the association between
      infant self-regulation problems and maternal mindfulness. CONCLUSION: These
      results suggest that maternal mindfulness during pregnancy may have positive
      effects on infant development. This association may be mediated by reduced
      anxiety symptoms in pregnant women who score high on mindfulness. Additional
      replication studies are needed using objective measures of infant
      behavioural/emotional outcomes and mindfulness of the mother during child
      development.

PMID- 25577498
TI  - Beyond lip service and box ticking: how effective patient engagement is integral
      to the development and delivery of patient-reported outcomes.
AB  - BACKGROUND: In the UK, demonstration of patient and public involvement (PPI) is
      now a funding requirement. Despite advice being available to researchers
      regarding PPI, levels of engagement are variable. Patient involvement has been at
      the core of the Leeds Psychosocial Oncology and Clinical Practice Research Group
      since 2007 when a local Research Advisory Group (RAG) was established. In
      addition, we work with experienced patient advocates from national groups.
      METHODS: The RAG is led by designated researchers who manage and communicate with
      members. The RAG is invited to twice yearly meetings with the full research team
      when study findings are disseminated and advice sought. The meetings are also an
      opportunity to socialise and thank members. Effective partnerships and engagement
      require good communication, building relationships over time and tailoring
      involvement to individuals' skills and experience. RESULTS: Patients have been
      involved in design, planning new projects and assisting with grant proposals;
      development, pilot testing of interview strategies and question generation,
      project steering groups and management teams, development of self-management
      advice for online patient portals; implementation, extensive beta testing of new
      questionnaire builder software to enable collection of online patient-reported
      outcomes (PRO) and study websites, cognitive interviews to develop PRO items;
      dissemination, co-authorship of papers and presentations,
      attendance/representation of the group at conferences. CONCLUSION: The
      involvement of patient advocates is integral to ensuring PRO development remains
      patient-centred. Having a co-operative, well-established local PPI group and
      nationally active patient collaborators has had a rewarding and significant
      impact on our research programmes.

PMID- 25577499
TI  - The impact of social support at home on health-related quality of life among
      veterans with spinal cord injury participating in a supported employment program.
AB  - PURPOSE: To investigate the impact of social support at home on health-related
      quality of life (HRQOL) as measured by the VR-6D utility index for spinal cord
      injury (SCI) veterans participating in a program of supported employment (SE).
      METHODS: We calculated a preference-based utility index called the VR-6D from the
      responses from a 36-item instrument called the VR-36. We estimated a growth curve
      model to examine the change in the VR-6D utility index over time adjusting for
      social support status, demographics, and chronic comorbidities. RESULTS: Study
      participants experienced an increase in HRQOL over time. The initial level and
      the rate of increase in HRQOL varied by groups based on their support status. The
      rate of increase in HRQOL diminished over time. Participants reporting no support
      at home experienced lower initial HRQOL but reached the same level of those who
      reported having support at home by the ninth month of follow-up. Quality-adjusted
      life-years, as measured by the area under the curves, were approximately the same
      for both groups after 2 years. CONCLUSIONS: Differences in the rate of change in
      HRQOL by support status have important implications for evaluations of SE
      programs. Participants in this program of SE experienced improvement in HRQOL
      beyond 12 months and extending to 2 years. Follow-up times for evaluations should
      extend beyond 12 months to assess complete improvements in HRQOL. Future
      comparison groups in comparative effectiveness evaluations of SE need to be
      balanced carefully on support status in addition to other factors.

PMID- 25577500
TI  - Serum SmD autoantibody proteomes are clonally restricted and share variable
      region peptides.
AB  - Recent advances in mass spectrometry-based proteomic methods have allowed
      variable (V)-region peptide signatures to be derived from human autoantibodies
      present in complex serum mixtures. Here, we analysed the clonality and V-region
      composition of immunoglobulin (Ig) proteomes specific for the immunodominant SmD
      protein subunit of the lupus-specific Sm autoantigen. Precipitating SmD-specific
      IgGs were eluted from native SmD-coated ELISA plates preincubated with sera from
      six patients with systemic lupus erythematosus (SLE) positive for anti-Sm/RNP.
      Heavy (H)- and light (L)-chain clonality and V-region sequences were analysed by
      2-dimensional gel electrophoresis and combined de novo database mass
      spectrometric sequencing. SmD autoantibody proteomes from all six patients with
      SLE expressed IgG1 kappa restricted clonotypes specified by IGHV3-7 and IGHV1-69
      H-chains and IGKV3-20 and IGKV2-28 L-chains, with shared and individual V-region
      amino acid replacement mutations. Clonotypic sharing and restricted V-region
      diversity of systemic autoimmunity can now be extended from the Ro/La cluster to
      Sm autoantigen and implies a common pathway of anti-Sm autoantibody production in
      unrelated patients with SLE. 

PMID- 25577497
TI  - Cancer chemotherapy and cardiac arrhythmias: a review.
AB  - Cardiovascular toxicity is a potential complication of cancer chemotherapy (CC)
      that increases the morbidity and mortality of cancer patients. Cardiac
      arrhythmias have been reported as an adverse effect of many chemotherapeutic
      drugs, including novel targeted therapies. The relationship between chemotherapy
      and arrhythmias has not been well-established and the proarrhythmogenic
      mechanisms remain uncertain as they can be the result of a direct
      electrophysiological effect or of changes in cardiac structure and function,
      including myocardial ischaemia and heart failure, which create an arrhythmogenic
      substrate. In this review we summarise available evidence of proarrhythmia
      induced by CC, discuss the possible mechanisms involved in this adverse effect
      and emphasise the importance of cardiac monitoring for the early diagnosis,
      intervention and surveillance of those patients more susceptible to develop
      proarrhythmia in an attempt to reduce the morbidity and mortality. Oncologists
      should be fully aware of proarrhythmia and the close collaboration between
      cardiologists and oncologists would result in a better cardiovascular assessment,
      risk stratification, cardiac monitoring and treatment during CC and during the
      follow-up. The final objective is to understand the mechanisms of proarrhythmia
      and evaluate its real incidence and clinical relevance so as to select the safest
      and most effective treatment for cancer patients. 

PMID- 25577501
TI  - Applicability and evaluation of a psychosocial intervention program for childhood
      cancer patients.
AB  - PURPOSE: The purpose of this study is to explore the applicability of a
      psychosocial intervention in childhood cancer patients. METHODS: This
      individualized structured psychosocial program to enhance social-emotional
      functioning and coping with disease-related effects includes six sessions for
      children and two sessions for parents. This program was part of a combined
      intervention with physical exercise. Questionnaires are used to evaluate
      completion of the psychosocial intervention, coping and satisfaction with the
      psychosocial intervention by patients and psychologists, and ranking of the
      individual topics by patients, parents, and psychologists. RESULTS: Of the 30
      patients (mean age 13.0 (SD 3.0); 53.3 % male; 30 % still on treatment) who
      participated in the psychosocial intervention, two dropped out due to medical
      complications and one due to lack of time; 90 % completed the psychosocial
      intervention. Overall, patients liked participation in the intervention (4.2 on a
      5-point scale; SD 0.8) and were positive about the psychologists (8.1 on a 10
      point scale; SD 1.3). Psychologists rated the intervention on several points
      (e.g., clarity of the manual and content of the intervention), and mean scores
      ranged from 7.1 (SD 1.1) to 8.6 (SD 0.9) on 10-point scales. Minor adaptations
      were suggested by patients and psychologists, including customizing according to
      age and a more patient-tailored approach. CONCLUSION: This psychosocial
      intervention for childhood cancer patients appears to be applicable. Future
      studies need to establish whether this intervention combined with a physical
      exercise intervention actually improves psychosocial functioning of childhood
      cancer patients. When proven effective, this combined intervention can be offered
      to childhood cancer patients and may enhance their physical health and quality of
      life.

PMID- 25577502
TI  - Exercise intervention for patients diagnosed with operable non-small cell lung
      cancer: a qualitative longitudinal feasibility study.
AB  - PURPOSE: The purpose was to explore operable lung cancer patient experiences with
      an exercise intervention from a longitudinal perspective according to patient
      motivation and patient perceived benefits and barriers of exercise. METHODS:
      Nineteen patients enrolled in an exercise intervention 2 weeks post-surgery
      participated in qualitative interviews at three time points. A criteria sampling
      strategy was applied. Ricoeur's phenomenological hermeneutical philosophy
      inspired the analysis. RESULTS: Patients initiated exercising median 15 days
      postoperative. Eight patients included in the interview study dropped out of the
      intervention due to side effects of chemotherapy (n = 3) and external
      circumstances (n = 5). The mean attendance rate for the eleven participants who
      completed the intervention was 82 %. No patients experienced severe adverse
      events. Motivation for participation included patients' expectations of physical
      benefits and the security of having professionals present. Patients experienced
      physical and emotional benefits and affirmed their social identity. Barriers were
      primarily related to side effects of chemotherapy. CONCLUSION: The exercise
      intervention was undertaken safely by operable lung cancer patients initiated 2
      weeks after surgery. The intervention put the patients on track to a healthier
      lifestyle regarding physical activity and smoking. The study indicates that
      exercise initiated early in the treatment trajectory is beneficial for operable
      lung cancer patients and especially for those who were physically active and
      motivated pre-illness and who did not experience side effect of treatment.

PMID- 25577503
TI  - Serum fibronectin 1 and ApoE levels increase with risk of lymphedema in Korean
      breast cancer survivors.
AB  - PURPOSE: Lymphedema is an irreversible disorder often seen as a postoperative
      side effect in breast cancer survivors. We aimed to identify serum factors that
      are associated with lymphedema risk in breast cancer survivors. METHODS: This
      study recruited 60 volunteer breast cancer survivors. Participants were
      classified into either a CTRL group who underwent sentinel lymph node biopsy
      (SLNB), a RISK group who underwent axillary lymph node dissection (ALND) with
      removal of fewer than five lymph nodes, or an LE group who underwent ALND with
      removal of more than five lymph nodes. Bioimpedance was measured to determine the
      ratio of extracellular water (ECW) to total cellular water (TCW) and single
      frequency bioimpedance analysis (SFBIA) ratios. Serum lipid profiles were
      compared among the groups using label-free quantitative proteomics with the nano
      liquid chromatography (LC)-tandem mass spectrometer (MS/MS) and emPAI method.
      RESULTS: The CTRL, RISK, and LE groups had similar body weights and body mass
      indexes (BMIs) (<25 kg/m(2)). The LE group showed a higher grade of lymphedema
      severity compared to the RISK and CTRL groups. Lymphedema indices such as the
      ECW/TCW ratio and SFBIA ratio at 1 and 5 kHz were greatly increased in the LE
      group. Serum total cholesterol (total-C) level was higher in the LE group without
      affecting atherogenic index. Serum proteomics revealed that fibronectin 1 (FN1),
      apolipoprotein E (ApoE), antithrombin (ANT3), and complement C4 had different
      abundance values among the groups. ELISA confirmed that FN1 and ApoE were
      significantly elevated in both the RISK and LE groups compared to the CTRL group.
      CONCLUSIONS: Changes in serum FN1 and ApoE levels were detected prior to changes
      in serum total-C level and lymphedema indices such as SFBIA ratio. Therefore,
      elevation in serum FN1 and ApoE concentrations could likely be used to monitor
      the risk of lymphedema in breast cancer survivors.

PMID- 25577504
TI  - A comparison of the effectiveness of complex decongestive physiotherapy and
      stellate ganglion block with triamcinolone administration in breast cancer
      related lymphedema patients.
AB  - PURPOSE: This study aims to investigate the comparison of effectiveness between
      stellate ganglion block (SGB) and complex decongestive physiotherapy (CDT) in
      breast cancer-related lymphedema (BCRL) patients. METHODS: The study is a
      retrospective matched cohort study. A total of 60 subjects who had secondary
      lymphedema after breast cancer treatments were included in this study. Thirty
      subjects who had SGB were matched with other 30 subjects treated with CDT, which
      is the standard therapy for BCRL. The groups were matched for age, duration of
      lymphedema, type of surgery, and history of lymph node dissection. SGB subjects
      received SGB three times, once every 2 weeks and CDT subjects were treated for 2
      weeks. The circumferences of the forearm and upper arm were used as the outcome
      variable. These parameters were measured with baseline value before each
      treatment and repeated the evaluation after the treatments. We investigated the
      difference of circumferences within each treatment and compared the clinical
      effect between treatments. RESULTS: Sixty subjects (mean age 58.2 +/- 8.7) were
      treated with CDT and SGB each. There was no significant difference in demographic
      data including cancer treatment. The mean circumferences of the forearm and upper
      arm after CDT significantly reduced; forearm from 24.91 to 23.87 cm and upper arm
      from 30.52 to 29.58 cm (p < 0.001). And the clinical effect of SGB was also
      significant; forearm from 24.90 to 23.64 cm and upper arm from 30.96 to 29.16 cm
      (p < 0.001). The differences of the forearm between CDT and SGB was not
      significant, but the circumference of the upper arm was more reduced after SGB
      treatment (1.81 +/- 1.21 cm) than CDT (0.94 cm +/- 0.78 cm) (p < 0.01).
      CONCLUSIONS: SGB is an effective treatment which can reduce the circumference of
      arm in breast cancer-related lymphedema patients and could be an alternative
      treatment for lymphedema.

PMID- 25577505
TI  - Coming and going: predicting the discharge of cancer patients admitted to a
      palliative care unit: easier than thought?
AB  - PURPOSE: Discharging a patient admitted to an inpatient palliative care unit
      (PCU) is a major challenge. A predictor of the feasibility of home discharge at
      the time of admission would be very useful. We tried to identify such predictors
      in a prospective observational study. METHODS: Sixty patients with advanced
      cancer admitted to a PCU were enrolled. Sociodemographic data were recorded and a
      panel of laboratory tests performed. The Karnofsky performance status scale (KPS)
      and the palliative performance scale (PPS) were determined. A palliative care
      physician and nurse independently predicted whether the patient would die at the
      ward. The association of these variables with home discharge or death at the PCU
      was determined. RESULTS: Sixty patients (26 men and 34 women) with advanced
      cancer were included in the study. Discharge was achieved in 45 % of patients,
      while 55 % of patients died at the PCU. The median stay of discharged patients
      was 15.2 days, and the median stay of deceased patients 13.6 days. Median KPS and
      PPS on admission was 56.2 % for the entire group and significantly higher for
      discharged patients (60.7 %) compared to deceased patients (52.4 %). Median BMI
      on admission was 22.8 in the entire group and was similar in discharged and
      deceased patients. No correlation was found between a panel of sociodemographic
      variables and laboratory tests with regard to discharge or death. In a binary
      logistic regression model, the probability of discharge as estimated by the
      nurse/physician and the KPS and PPS were highly significant (p = 0.008).
      CONCLUSION: Estimation by a nurse and a physician were highly significant
      predictors of the likelihood of discharge and remained significant in a
      multivariate logistic regression model including KPS and PPS. Other variables,
      such as a panel of laboratory tests or sociodemographic variables, were not
      associated with discharge or death.

PMID- 25577506
TI  - Risk of febrile neutropenia in patients receiving emerging chemotherapy regimens
      for breast cancer.

PMID- 25577507
TI  - The effects of subthalamic deep brain stimulation on metaphor comprehension and
      language abilities in Parkinson's disease.
AB  - The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in
      Parkinson's disease (PD) on different language abilities are still controversial
      and its impact on high-level language abilities such as metaphor comprehension
      has been overlooked. The aim of this study was to determine the effects of STN
      electrical stimulation on metaphor comprehension and language abilities such as
      lexical and semantic capacities. Eight PD individuals with bilateral STN-DBS were
      first evaluated OFF-DBS and, at least seven weeks later, ON-DBS. Performance on
      metaphor comprehension, lexical decision, word association and verbal fluency
      tasks were compared ON and OFF-DBS in addition to motor symptoms evaluation. STN
      stimulation had a significant beneficial effect on motor symptoms in PD. However,
      this stimulation did not have any effect on metaphor comprehension or any other
      cognitive ability evaluated in this study. These outcomes suggest that STN
      stimulation may have dissociable effects on motor and language functions. 

PMID- 25577508
TI  - The distinctive contrast of multiple sclerosis epidemiology between Persians and
      Armenian minority community of Isfahan city, Iran.

PMID- 25577509
TI  - Postencephalitic parkinsonism and selective involvement of substantia nigra.

PMID- 25577512
TI  - Analysis of Light Gathering Abilities of Dynamically Solidified Micro-lenses, and
      Their Implementation to Improve Sensitivity of Fluorescent PCR Micro-detectors.
AB  - Fluorescent polymerase chain reaction (PCR) is becoming the preferred method of
      quantitative analysis due to its high specificity and sensitivity. We propose to
      use a new kind of micro-lens, dynamically solidified with optic glue, to improve
      the sensitivity of fluorescent PCR micro-detector. We developed light ray track
      equations for these lenses and used them to calculate relative light intensity
      distribution curve for stimulation lenses and illumination point probability
      distribution curve for detection lenses. We manufactured dynamically solidified
      micro-lenses using optic glue NOA61, and measured their light gathering ability.
      Lenses with radius/thickness (R/H) ratio of 4 reached light focusing ratio of
      3.85 (stimulation lens) and photon collection efficiency of 0.86 (detection
      lens). We then used dynamically solidified lenses in PCR fluorescence micro
      detector and analyzed their effect on the detector sensitivity. We showed that
      the use of dynamically solidified micro-lenses with R/H = 4 resulted in over 4.4
      fold increased sensitivity of the detector. 

PMID- 25577511
TI  - Icaritin Sensitizes Human Glioblastoma Cells to TRAIL-Induced Apoptosis.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been
      considered to be one of the most promising candidates in research on treatments
      for cancer, because it induces apoptosis in a wide variety of cancer cells but
      not in most normal human cell types. However, many cells including glioblastoma
      (GBM) cells are resistant to TRAIL-induced apoptosis, which limits the potential
      application of TRAIL in cancer therapy. Icaritin, a hydrolytic product of icariin
      from Epimedium Genus, has been identified as a potential therapeutic and
      preventive agent in renal cell carcinoma and breast cancer. In this study, we
      investigated whether Icaritin treatment could modulate TRAIL-induced apoptosis in
      GBM. The effect of icaritin on TRAIL sensitivity was assessed in human GBM U87
      and U373 cells. The underlying regulatory cascades were approached by biochemical
      and pharmacological strategies. We found that nontoxic concentration of icaritin
      alone had no significant effect on the level of apoptosis, but a combination
      treatment of TRAIL and icaritin caused a significantly more profound apoptosis.
      The sensitization was accompanied by c-FLIP down-regulation and inhibition of NF
      kappaB activity. Studies have further demonstrated that silencing NF-kappaB alone
      was sufficient to down-regulate c-FLIP expression and sensitized both tested
      cells to TRAIL-induced apoptosis. These data suggest that icaritin sensitizes
      TRAIL-induced tumor cell apoptosis via suppression of NF-kappaB-dependent c-FLIP
      expression, providing in vitro evidence supporting the notion that icaritin is a
      potential sensitizer of TRAIL in anticancer therapy against human GBM. 

PMID- 25577510
TI  - Altered human brain anatomy in chronic smokers: a review of magnetic resonance
      imaging studies.
AB  - Cigarette smoking is becoming more prevalent in developing countries, such as
      China, and is the largest single cause of preventable death worldwide. New
      emerging reports are highlighting how chronic cigarette smoking plays a role in
      neural dysfunctions, such as cognitive decline. Basic animal experimental studies
      have shown that rats undergo persistent pathological brain changes after being
      given chronic levels of nicotine. What is perhaps less appreciated is the fact
      that chronic cigarette smoking induces subtle anatomical changes in the human
      brain. Consequently, this chapter aims to summarize and integrate the existing
      magnetic resonance imaging studies on both gray- and white-matter marcostructural
      and microstructural changes. The reviewed studies demonstrate that chronic
      cigarette smoking results in discrete and localized alterations in brain region
      tissue (both the gray and white matter of different brain regions), which may, in
      part, be responsible for different neural dysfunctions. In addition, we further
      discuss the possible pathological and neurobiological mechanisms of these
      nicotinic effects on the brain tissue. We will also address the limitations of
      the current studies on this issue and identify opportunities for future research.

PMID- 25577513
TI  - Z-11 trial and rethinking axillary reverse mapping.

PMID- 25577514
TI  - Breast sentinel lymph node navigation with three-dimensional computed tomography
      lymphography: a 12-year study.
AB  - PURPOSE: To evaluate the utility of three-dimensional (3D) computed tomography
      (CT)-lymphography (LG) breast sentinel lymph node navigation in our institute.
      PATIENTS AND METHODS: Between 2002 and 2013, we preoperatively identified
      sentinel lymph nodes (SLNs) in 576 clinically node-negative breast cancer
      patients with T1 and T2 breast cancer using 3D CT-LG method. SLN biopsy (SLNB)
      was performed in 557 of 576 patients using both the images of 3D CT-LG for
      guidance and the blue dye method. RESULTS: Using 3D CT-LG, SLNs were visualized
      in 569 (99%) of 576 patients. Of 569 patients, both lymphatic draining ducts and
      SLNs from the peritumoral and periareolar areas were visualized in 549 (96%)
      patients. Only SLNs without lymphatic draining ducts were visualized in 20
      patients. Drainage lymphatic pathways visualized with 3D CT-LG (549 cases) were
      classified into four patterns: single route/single SLN (355 cases, 65%), multiple
      routes/single SLN (59 cases, 11%) single route/multiple SLNs (62 cases, 11%) and
      multiple routes/multiple SLNs (73 cases, 13%). SLNs were detected in 556 (99.8%)
      of 557 patients during SLNB. CONCLUSION: CT-LG is useful for preoperative
      visualization of SLNs and breast lymphatic draining routes. This preoperative
      method should contribute greatly to the easy detection of SLNs during SLNB.

PMID- 25577515
TI  - Interpretation of Logical Words in Mandarin-Speaking Children with Autism
      Spectrum Disorders: Uncovering Knowledge of Semantics and Pragmatics.
AB  - This study investigated the interpretation of the logical words 'some' and
      'every...or...' in 4-15-year-old high-functioning Mandarin-speaking children with
      autism spectrum disorders (ASD). Children with ASD performed similarly to typical
      controls in demonstrating semantic knowledge of simple sentences with 'some', and
      they had delayed knowledge of the complex sentences with 'every...or...'.
      Interestingly, the children with ASD had pragmatic knowledge of the scalar
      implicatures of these logical words, parallel to those of the typical controls.
      Taken together, the interpretation of logical words may be a relative strength in
      children with ASD. It is possible that some aspects of semantics and pragmatics
      may be selectively spared in ASD, due to the contribution the language faculty
      makes to language acquisition in the ASD population. 

PMID- 25577516
TI  - Comparative analysis of clinicoradiologic characteristics of lung adenocarcinomas
      with ALK rearrangements or EGFR mutations.
AB  - OBJECTIVE: To compare the clinicoradiologic features of tumours with echinoderm
      anaplastic lymphoma kinase (ALK) rearrangements, epidermal growth factor receptor
      (EGFR) mutations, or wild type (WT) for both genes in a cohort of patients with
      lung adenocarcinoma to identify useful characteristics of different gene
      statuses. METHODS: In 346 lung adenocarcinoma patients, ALK rearrangements were
      confirmed with fluorescence in situ hybridisation, and EGFR mutations were
      determined by pyrosequencing assay. Patients were divided into three groups: ALK
      rearrangement (ALK+ group, n = 48), EGFR mutation (EGFR+ group, n = 166), and WT
      for both genes (WT group, n = 132). Chest computed tomography (CT) examinations
      were performed in all patients. The percentages of ground-glass opacity volume
      (pGGO) and tumour shadow disappearance rate (TDR) were measured using semi
      automated nodule assessment software. RESULTS: The pGGO was significantly lower
      in the ALK+ group (25.1 % +/- 24.3) than in the EGFR+ group (37.2 % +/- 25.7, p <
      0.001) and the WT group (36.1 % +/- 24.6, p = 0.001). The TDR in the ALK+ group
      (17.3 % +/- 25.1) was significantly lower than in the EGFR+ group (26.8 % +/-
      24.9, p = 0.002) and the WT group (25.7 % +/- 24.6, p = 0.003). CONCLUSIONS:
      Solid pattern with lower incidence of lobulated border, finely spiculated
      margins, pleural retraction, and bubble-like lucency on CT imaging are the main
      characteristics of ALK rearrangement tumours. KEY POINTS: * EGFR/ALK testing is
      recommended for lung adenocarcinoma patients for EGFR/ALK-targeted TKI therapy. *
      EGFR /ALK testing is restricted by limited tissue samples and cost pressures. *
      Lower pGGO and TDR are the main clinicoradiological characteristics of ALK+
      tumours. * pGGO and TDR are predictive factors for selecting patients for
      ALK/EGFR testing.

PMID- 25577518
TI  - The effect of computer-aided detection markers on visual search and reader
      performance during concurrent reading of CT colonography.
AB  - OBJECTIVE: We aimed to identify the effect of computer-aided detection (CAD) on
      visual search and performance in CT Colonography (CTC) of inexperienced and
      experienced readers. METHODS: Fifteen endoluminal CTC examinations were recorded,
      each with one polyp, and two videos were generated, one with and one without a
      CAD mark. Forty-two readers (17 experienced, 25 inexperienced) interpreted the
      videos during infrared visual search recording. CAD markers and polyps were
      treated as regions of interest in data processing. This multi-reader, multi-case
      study was analysed using multilevel modelling. RESULTS: CAD drew readers'
      attention to polyps faster, accelerating identification times: median 'time to
      first pursuit' was 0.48 s (IQR 0.27 to 0.87 s) with CAD, versus 0.58 s (IQR 0.35
      to 1.06 s) without. For inexperienced readers, CAD also held visual attention for
      longer. All visual search metrics used to assess visual gaze behaviour
      demonstrated statistically significant differences when "with" and "without" CAD
      were compared. A significant increase in the number of correct polyp
      identifications across all readers was seen with CAD (74 % without CAD, 87 % with
      CAD; p < 0.001). CONCLUSIONS: CAD significantly alters visual search and polyp
      identification in readers viewing three-dimensional endoluminal CTC. For polyp
      and CAD marker pursuit times, CAD generally exerted a larger effect on
      inexperienced readers. KEY POINTS: * Visual gaze is attracted by computer
      assisted detection (CAD) marks on polyps * Inexperienced readers' gaze is
      affected more by CAD than experienced readers. * CAD marks could mean that the
      unannotated endoluminal surface is relatively neglected. * Correct polyp
      identification is increased significantly by CAD.

PMID- 25577517
TI  - Distribution and natural course of intracranial vessel wall lesions in patients
      with ischemic stroke or TIA at 7.0 Tesla MRI.
AB  - OBJECTIVES: Previous studies using intracranial vessel wall MRI techniques showed
      that over 50 % of patients with ischemic stroke or TIA had one or more
      intracranial vessel wall lesions. In the current study, we assessed the
      preferential location of these lesions within the intracranial arterial tree and
      their potential changes over time in these patient groups. METHODS: Forty-nine
      patients with ischemic stroke (n = 25) or TIA (n = 24) of the anterior cerebral
      circulation underwent 7.0 T MRI, including a T1-weighted magnetization
      preparation inversion recovery turbo-spin-echo (MPIR-TSE) sequence within one
      week and approximately one month after symptom onset. Intracranial vessel wall
      lesions were scored for multiple locations within the arterial tree and
      differences between one-week and one-month images. RESULTS: At baseline, 132
      intracranial vessel wall lesions were found in 41 patients (84 %), located
      primarily in the anterior cerebral circulation (74 %), with a preferential
      location in the distal internal carotid artery and M1 and M2 segments of the
      middle cerebral artery. During follow-up, presence or enhancement patterns
      changed in 14 lesions (17 %). CONCLUSIONS: A large burden of intracranial vessel
      wall lesions was found in both the anterior and posterior cerebral circulation.
      Most lesions were found to be relatively stable, possibly indicating a more
      generalized atherosclerotic process. KEY POINTS: * Intracranial vessel wall
      lesions are present in patients with varying cerebrovascular diseases. *
      Intracranial vessel wall 7.0 T MRI provides information on preferential location
      and natural course. * Distal ICA and M1 and M2 segments of MCA are predilection
      sites. * 83 % of lesions found remained stable, possibly indicating more
      generalized atherosclerosis.

PMID- 25577519
TI  - The pathophysiology of the chronic cardiorenal syndrome: a magnetic resonance
      imaging study.
AB  - OBJECTIVE: To study the association of renal function with renal perfusion and
      renal parenchymal structure (T1 relaxation) in patients with chronic heart
      failure (HF). METHODS: After IRB approval, 40 participants were enrolled
      according to HF and renal function status [10 healthy volunteers < 40 years; 10
      healthy age-matched volunteers; 10 HF patients eGFR > 60 ml/min/1.73 m(2); 10 HF
      patients eGFR < 60 ml/min/1.73 m(2)] and assessed by MRI. To be eligible for
      enrolment all HF patients with renal dysfunction (RD) needed to be diagnosed as
      having chronic cardiorenal syndrome based on current guidelines. Patients with
      primary kidney disease were excluded. RESULTS: Renal cortical perfusion
      correlated with eGFR values (r = 0.52;p < 0.01) and was similar between HF
      patients with and without RD (p = 0.27). T1 relaxation correlated negatively with
      eGFR values (r = -0.41;p > 0.01) and was higher in HF patients compared to
      volunteers (1121 +/- 102 ms vs. 1054 +/- 65 ms;p = 0.03). T1 relaxation was
      selectively prolonged in HF patients with RD (1169 ms +/- 100 vs. HF without RD
      1067 ms +/- 79;p = 0.047). In linear regression analyses coronary artery disease
      (p = 0.01), hypertension (p = 0.04), and diabetes mellitus (p < 0.01) were
      associated with T1 relaxation. CONCLUSION: RD in HF is not primarily mediated by
      decreased renal perfusion. Instead, chronic reno-parenchymal damage, as indicated
      by prolonged T1 relaxation, appears to underly chronic cardiorenal syndrome. KEY
      POINTS: * The pathophysiology underlying chronic cardiorenal syndrome is not
      completely understood. * Chronic cardiorenal syndrome is independent of cardiac
      output or renal perfusion. * Renal T 1 relaxation appears to be prolonged in HF
      with renal impairment. * Renal T 1 relaxation is associated with classic
      cardiovascular risk factors. * Association of renal T 1 relaxation with
      parenchymal damage should be validated further.

PMID- 25577520
TI  - Analysis of normal-appearing white matter of multiple sclerosis by tensor-based
      two-compartment model of water diffusion.
AB  - OBJECTIVES: To compare the significance of the two-compartment model, considering
      diffusional anisotropy with conventional diffusion analyzing methods regarding
      the detection of occult changes in normal-appearing white matter (NAWM) of
      multiple sclerosis (MS). METHODS: Diffusion-weighted images (nine b-values with
      six directions) were acquired from 12 healthy female volunteers (22-52 years old,
      median 33 years) and 13 female MS patients (24-48 years old, median 37 years).
      Diffusion parameters based on the two-compartment model of water diffusion
      considering diffusional anisotropy was calculated by a proposed method. Other
      parameters including diffusion tensor imaging and conventional apparent diffusion
      coefficient (ADC) were also obtained. They were compared statistically between
      the control and MS groups. RESULTS: Diffusion of the slow diffusion compartment
      in the radial direction of neuron fibers was elevated in MS patients (0.121 * 10(
      3) mm2/s) in comparison to control (0.100 * 10(-3) mm(2)/s), the difference being
      significant (P = 0.001). The difference between the groups was not significant in
      other comparisons, including conventional ADC and fractional anisotropy (FA) of
      diffusion tensor imaging. CONCLUSION: The proposed method was applicable to
      clinically acceptable small data. The parameters obtained by this method improved
      the detectability of occult changes in NAWM compared to the conventional methods.
      KEY POINTS: * Water diffusion was compared between the controls and multiple
      sclerosis patients. * A two-compartment model, considering diffusional anisotropy
      was selected for water diffusion analysis. * Axial and radial diffusion of fast
      and slow diffusion components were evaluated. * A new method was developed to
      obtain the metrics stably. * The metrics indicated high detectability of slight
      differences between the groups.

PMID- 25577522
TI  - Use of diagnostic dynamic contrast-enhanced (DCE)-MRI for targeting of soft
      tissue tumour biopsies at 3T: preliminary results.
AB  - OBJECTIVES: To test the feasibility and accuracy of MR-guided soft tissue tumour
      biopsy at 3T, using the dynamic contrast-enhanced (DCE) information from staging
      MRI for intralesional targeting. METHODS: After obtaining written informed
      consent for this institutional review board-approved study, 53 patients with
      suspected soft tissue tumours prospectively underwent preoperative staging MRI at
      3T, including DCE, and subsequent MR-guided core needle biopsy. In 44/53 cases,
      DCE was heterogeneous and was used for intralesional biopsy targeting. Surgical,
      whole-specimen histology was used as the gold standard in 43/44 patients and
      revealed 42 soft tissue tumours (24 men; 18 women; mean age, 52 years; range, 19 
      84). RESULTS: Final surgical histology revealed eight benign lesions, six
      tumours of intermediate dignity, and 28 malignancies. All malignancies had shown
      heterogeneous DCE. The diagnostic yield of the biopsies was 100% (42/42).
      Histological accuracy rates of biopsy were 100% in predicting the dignity (42/42;
      95% CI [0.916 - 1.000]), 95.2% for the tissue-specific entity (40/42; 95% CI
      [0.847 - 0.987]), and 90.5% for the tumour grade (38/42; 95% CI [0.779 - 0.962]).
      CONCLUSIONS: Our preliminary study indicates that biopsy of soft tissue tumours
      can be performed accurately and safely with DCE targeted MR-guidance at 3T, using
      a combined staging/biopsy MRI protocol. KEY POINTS: * MR-guided soft tissue
      tumour biopsy using DCE for intralesional targeting is feasible. * Targeting by
      staging-MRI allows reliable planning of the biopsy approach. * The method seems
      accurate and safe as a combined staging/biopsy procedure in outpatients. * DCE
      targeted biopsy seems useful in challenging large and heterogeneous tumours.

PMID- 25577521
TI  - Feasibility study of novel endoscopic Cerenkov luminescence imaging system in
      detecting and quantifying gastrointestinal disease: first human results.
AB  - OBJECTIVES: Cerenkov luminescence imaging (CLI) provides potential to use
      clinical radiotracers for optical imaging. The goal of this study was to present
      a newly developed endoscopic CLI (ECLI) system and illustrate its feasibility and
      potential in distinguishing and quantifying cancerous lesions of the GI tract.
      METHODS: The ECLI system was established by integrating an electron-multiplying
      charge-coupled device camera with a flexible fibre endoscope. Phantom experiments
      and animal studies were conducted to test and illustrate the system in detecting
      and quantifying the presence of radionuclide in vitro and in vivo. A pilot
      clinical study was performed to evaluate our system in clinical settings.
      RESULTS: Phantom and mice experiments demonstrated its ability to acquire both
      the luminescent and photographic images with high accuracy. Linear quantitative
      relationships were also obtained when comparing the ECLI radiance with the
      radiotracer activity (r (2) = 0.9779) and traditional CLI values (r (2) =
      0.9025). Imaging of patients revealed the potential of ECLI in the identification
      and quantification of cancerous tissue from normal, which showed good consistence
      with the clinical PET examination. CONCLUSIONS: The new ECLI system shows good
      consistence with the clinical PET examination and has great potential for
      clinical translation and in aiding detection of the GI tract disease. KEY POINTS:
      * CLI preserves the characteristics of both optical and radionuclide imaging. *
      CLI provides great potential for clinical translation of optical imaging. * The
      newly developed endoscopic CLI (ECLI) has quantification and imaging capacities.
      * GI tract has accessible open surfaces, making ECLI a potentially suitable
      technique. * Cerenkov endoscopy has great clinical potential in detecting GI
      disease.

PMID- 25577523
TI  - Prognostic potential of initial CT changes for progression-free survival in
      gefitinib-treated patients with advanced adenocarcinoma of the lung: a
      preliminary analysis.
AB  - OBJECTIVES: We aimed to determine whether initial tumour responses measured
      during short-term follow-up computed tomography (CT) examinations after baseline
      examinations would correlate with clinical outcomes in patients with non-small
      cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR)
      targeted therapy. METHODS: A total of 86 gefitinib-treated patients with advanced
      adenocarcinoma of the lung were retrospectively reviewed. All patients underwent
      baseline and short-term follow-up CT examinations. The new response criteria
      (NRC) by Lee et al. were used for the response evaluations. A Cox proportional
      hazards multiple regression model and Kaplan-Meier survival analyses were used to
      evaluate correlations between the initial tumour changes and progression-free and
      overall survival (PFS, OS). RESULTS: Better separation and smaller p values were
      observed for both PFS and OS when good and poor disease responses (as defined by
      NRC) were compared after excluding tumours with characteristic morphologies.
      Early tumour changes correlated with PFS in a size-dependent manner. Moreover, a
      stronger association was observed between size changes and PFS when
      characteristic morphology was also considered. CONCLUSIONS: Initial changes in
      tumour size during short-term post-treatment CT examinations could act as a
      potential prognostic imaging surrogate for PFS in gefitinib-treated patients with
      advanced adenocarcinoma of the lung. KEY POINTS: * Initial responses to gefitinib
      on computed tomography significantly correlate with clinical outcomes. *
      Regardless of morphology, size decrease greater than 30 % predicts prolonged
      progression-free and overall survival. * Combination of size and morphological
      changes yields prognostic independence regarding progression-free survival.

PMID- 25577524
TI  - DCE-MRI of the breast in a stand-alone setting outside a complementary strategy -
      results of the TK-study.
AB  - OBJECTIVES: To evaluate the accuracy of MRI of the breast (DCE-MRI) in a stand
      alone setting with extended indications. MATERIALS AND METHODS: According to the
      inclusion criteria, breast specialists were invited to refer patients to our
      institution for DCE-MRI. Depending on the MR findings, patients received either a
      follow-up or biopsy. Between 04/2006 and 12/2011 a consecutive total of 1,488
      women were prospectively examined. RESULTS: Of 1,488 included patients, 393
      patients were lost to follow-up, 1,095 patients were evaluated. 124 patients were
      diagnosed with malignancy by DCE-MRI (76 TP, 48 FP, 971 TN, 0 FN cases). Positive
      cases were confirmed by histology, negative cases by MR follow-ups or patient
      questionnaires over the next 5 years in 1,737 cases (sensitivity 100 %;
      specificity 95.2 %; PPV 61.3 %; NPV 100 %; accuracy 95.5 %). For invasive cancers
      only (DCIS excluded), the results were 63 TP; 27 FP; 971 TP and 0 FN (sensitivity
      100 %; specificity 97.2 %; PPV 70 %; NPV 100 %; accuracy 97.5 %). CONCLUSION: The
      DCE-MRI indications tested imply that negative results in DCE-MRI reliably
      exclude cancer. The results were achieved in a stand-alone setting (single
      modality diagnosis). However, these results are strongly dependent on reader
      experience and adequate technical standards as prerequisites for optimal
      diagnoses. KEY POINTS: * DCE-MRI of the breast has a high accuracy in finding
      breast cancer. * The set of indications for DCE-MRI of the breast is still very
      limited. * DCE-MRI can achieve a high accuracy in a 'screening-like' setting. *
      Accuracy of breast DCE-MRI is strongly dependent on technique and reader
      experience. * A negative DCE-MRI effectively excludes cancer.

PMID- 25577526
TI  - Adults with Prader-Willi syndrome have weaker bones: effect of treatment with GH
      and sex steroids.
AB  - Obesity has been considered to have a protective effect against the risk of
      fractures in adults. However, a high frequency of fracture is described in obese
      adults with Prader-Willi syndrome. To evaluate bone geometry, density and
      strength in a group of adult obese patients with Prader-Willi syndrome (PWS) and
      to examine the modulating effect on bone of treatment with growth hormone (GH)
      and sex steroids. This was a cross-sectional study performed in 41 (17 males, 24
      females) obese subjects with genetically confirmed PWS, aged 29.4 +/- 8.6 years.
      Forty-six healthy subjects (22 males and 24 females) served as controls.
      Digitalized X-rays were evaluated at the level of the 2nd metacarpal bone to
      assess bone geometry, i.e. cross-sectional area (CSA), cortical area (CA),
      medullary area (MA), metacarpal index (MI) and bone strength evaluated as bending
      breaking resistance index (BBRI). DEXA was also used to evaluate body composition
      and bone mineral density (total body, lumbar spine and femoral neck). PWS
      subjects, after adjusting for height and bone size, had a reduced CSA, CA and
      BBRI, while bone density was not different. GH treatment had a positive effect
      and sex steroids a negative effect on bone size and strength. PWS subjects showed
      a reduced bone size at the metacarpus leading to a reduced strength, while bone
      density was appropriate for size. GH treatment improves bone geometry but not
      bone density. Bone strength was significantly reduced in PWS patients who did not
      receive GH and had been treated with sex steroids.

PMID- 25577527
TI  - Out of the blue: the Grey-Turner's sign.

PMID- 25577528
TI  - Chronic obstructive pulmonary disease in the awareness of Polish society. Report
      from the public opinion survey by the Polish Respiratory Society and TNS Polska.
AB  - INTRODUCTION: It is assumed that signs of chronic obstructive pulmonary disease
      (COPD) can be found in 9.3% subjects of more than 40 years of age in general
      population in Poland. The aim of the presented survey was to assess knowledge of
      COPD in adult general population in Poland. MATERIAL AND METHODS: The study was
      performed in June 2013 in a representative sample of 1,000 persons of at least 15
      years of age in Poland, using standardized direct interview. RESULTS: In 2013
      only 3% Polish people admitted they had ever heard of COPD and knew what the
      acronym meant. Further 11% persons admitted having heard the term but had no
      further knowledge of the subject. Thus, the total of 14% persons in general
      population had previously heard of COPD albeit superficially. This figure is
      slightly higher as compared to the study performed in 2004. The second part of
      the study was performed in patients with COPD. Patients perceive the disease as a
      limiting factor in their daily lives, including negative impact on physical
      activity, causing loss of physical attractiveness (more often reported by women)
      or hurting their image of a strong and caring person (more often reported by
      men). The disease demands re-evaluation of the previous lifestyle, alienates
      patients from other people, and generates financial burden. Half of the entire
      studied general population either does not have any associations concerning
      potential causes of COPD or report various erroneous connotations (e.g. excessive
      alcohol consumption as a cause of the disease). Even patients with COPD have a
      similar view on causes of the disease. Importantly, the study revealed that
      awareness of the disease in smokers does not essentially differ from that in
      general public. Half of the res pondents admitted having no knowledge on
      prevention of COPD. CONCLUSIONS: There is an urgent need for widespread public
      education on preventive measures. Study results support the need of educating
      both healthy subjects and patients with COPD as to how effectively reduce the
      risk of developing the disease. One third of all respondents has no assumptions
      in this regard (i.e. explicitly declares having no knowledge at all on the
      subject), and more than 40% subjects have various misconceptions. Educators
      should therefore spread information about the disease but also correct these
      misconceptions.

PMID- 25577525
TI  - Standardized Index of Shape (SIS): a quantitative DCE-MRI parameter to
      discriminate responders by non-responders after neoadjuvant therapy in LARC.
AB  - OBJECTIVES: To investigate the potential of DCE-MRI to discriminate responders
      from non-responders after neoadjuvant chemo-radiotherapy (CRT) for locally
      advanced rectal cancer (LARC). We investigated several shape parameters for the
      time-intensity curve (TIC) in order to identify the best combination of
      parameters between two linear parameter classifiers. METHODS: Seventy-four
      consecutive patients with LARC were enrolled in a prospective study approved by
      our ethics committee. Each patient gave written informed consent. After surgery,
      pathological TNM and tumour regression grade (TRG) were estimated. DCE-MRI semi
      quantitative analysis (sqMRI) was performed to identify the best parameter or
      parameter combination to discriminate responders from non-responders in response
      monitoring to CRT. Percentage changes of TIC shape descriptors from the baseline
      to the presurgical scan were assessed and correlated with TRG. Receiver operating
      characteristic analysis and linear classifier were applied. RESULTS: Forty-six
      patients (62.2%) were classified as responders, while 28 subjects (37.8%) were
      considered as non-responders. sqMRI reached a sensitivity of 93.5% and a
      specificity of 82.1% combining the percentage change in Maximum Signal Difference
      (DeltaMSD) and Wash-out Slope (DeltaWOS), the Standardized Index of Shape (SIS).
      CONCLUSIONS: SIS obtains the best result in discriminating responders from non
      responders after CRT in LARC, with a cut-off value of -3.0%. KEY POINTS: * DCE
      MRI shape descriptors are investigated to assess preoperative CRT response in
      LARC. * Identification of the best TIC shape descriptors combination through a
      linear classifier. * Identification of a single MRI index to predict neoadjuvant
      treatment response.

PMID- 25577529
TI  - Fatigue in patients with inactive sarcoidosis does not correlate with lung
      ventilation ability or walking distance. Pilot Study.
AB  - INTRODUCTION: Fatigue is one of many symptoms reported by patients with
      sarcoidosis. It is believed that fatigue may be the cause of exercise intolerance
      and reduced quality of life in patients with sarcoidosis. The purpose of the work
      was to present the frequency of fatigue prevalence in patients with sarcoidosis
      and to investigate the correlation between fatigue and the results of pulmonary
      function tests and walking distance. MATERIAL AND METHODS: A total of 74 patients
      with sarcoidosis in a stable phase of the disease, not treated in the past with
      glucocorticoids or immunosuppressive drugs, and without indications for treatment
      at the time of the study were examined. In all patients fatigue evaluation was
      carried out with the use of the Fatigue Assessment Scale questionnaire (FAS);
      dyspnoea was assessed with the use of the Medical Research Council scale (MRC).
      Body Mass Index (BMI), spirometry, and a 6-minute walk test were additionally
      performed. The control group included 30 healthy volunteers who completed the
      FAS. RESULTS: In the examined group of patients fatigue was diagnosed in 36
      patients (50%), and in 5 (6.94%) - strong fatigue was observed. The remaining 31
      (43.06%) patients felt no fatigue. The average value of points obtained by FAS
      questionnaire in sarcoidosis patients was significantly higher than the
      respective value in the control group (p = 0.02). A significantly higher number
      of points by FAS questionnaire was observed in female patients with sarcoidosis
      (p = 0.04) in comparison to men. No significant statistical correlation between
      fatigue index FAS and BMI (r = 0.22, p = 0.11), FEV1 (r = -0.11, p = 0.3), FEV1%
      pred. (r = 0.01, p = 0.9), FVC (r = -0.03, p = 0.77), FEF25-75 (r = -0.23, p =
      0.1) and the distance in the six-minute walk test (6MWT) (r = -0.01, p = 0.9) was
      observed. However, there was a weak negative correlation between the age of the
      patients and the FAS index (r = -0.29, p = 0.01). CONCLUSIONS: Fatigue in
      patients with sarcoidosis does not correlate with the results of lung function
      tests or with walking distance in 6MWT.

PMID- 25577530
TI  - Tuberculosis among the homeless and inmates kept in custody and in penitentiary
      institutions in the Silesia region.
AB  - INTRODUCTION: There are more than 10 million prisoners in the world. Tuberculosis
      incidence is 10-100 times higher in prisoners than in the general population.
      Inmates have close contact with other prisoners and with prison workers and
      visitors, so tubercle bacilli may be easily spread. Most of the inmates come back
      to normal life and contact with the general population. The aim of the study was
      to assess active tuberculosis incidence among prisoners and homeless persons in
      the Silesia region. MATERIAL AND METHODS: In total 897 people entered the study,
      of whom 720 were Silesian penitentiary system inmates, and 177 were homeless.
      BACTEC MGIT fast TB detection system and GenoType Mycobacteria Direct test were
      used. Drug susceptibility testing was done using SIRE KIT and PZA KIT. RESULTS:
      Tuberculosis was diagnosed in 13 out of 897 persons (1.45%): in 11 out of 720
      inmates (1.53%) and in 2 out of 177 homeless persons (1.13%). Data concerning
      drug susceptibility were obtained for 11 persons. M. tuberculosis strains
      isolated from eight persons were susceptible to four first-line antituberculosis
      drugs (streptomycin, isoniazid, rifampin, ethambutol), while M. tuberculosis
      strains isolated from three persons were drug-resistant. One out of three
      isolated strains was resistant to ethambutol, but susceptible to streptomycin,
      isoniazid, rifampin, and pirazynamide. The second strain was resistant to
      streptomycin and pyrazinamide but susceptible to isoniazid, rifampin, and
      ethambutol. The third strain was susceptible to rifampin but resistant to the
      other four tested drugs. According to the obtained data, culture-positive
      pulmonary tuberculosis was 100 times more frequent in the examined population
      than in the general population of the Silesia region in the same period of time.
      CONCLUSIONS: The health project enabled effective detection of tuberculosis in
      risk groups and should be continued in the following years. The set of the
      applied diagnostic methods allowed the detection of in the studied subpopulations
      people suffering from tuberculosis. Patients were treated with antituberculosis
      drugs that would stop them from spreading the disease to other people.

PMID- 25577531
TI  - Lung-heart clinical crosstalk in the course of COPD exacerbation.
AB  - INTRODUCTION: COPD exacerbation is a life-threatening condition with acute
      dyspnoea caused by respiratory or circulatory distress. The significance and co
      presence of lung hyperinflation, bronchial obstruction, and changes in
      haemodynamics in the course of COPD exacerbation treatment have not been well
      described yet in course of a single study. Our aim was to evaluate the influence
      of COPD exacerbation treatment on bronchial obstruction, pulmonary
      hyperinflation, and possible changes of right and left ventricle haemodynamics in
      relation to the patient's clinical status. MATERIAL AND METHODS: A total of 40
      patients (90% males), 67 +/- 8 years old, with COPD were assessed pre- and post
      exacerbation treatment by the following: respiratory function tests,
      transthoracic echocardiography, 6MWT, endothelin-1 (ET-1) and NT-proBNP serum
      concentrations, and MRC scale. RESULTS: A significant decrease in RV%TLC (%) and
      mean pulmonary artery pressure (PAPmean) [mm Hg] was observed: pre -RV%TLC: 64.3
      +/- 9.0; post-RV%TLC 60.6 +/- 11.1; p = 0.03; pre-PAPmean: 41.2 +/- 11.2; post
      PAPmean: 39.1 +/- 12.1; p = 0.029, coupled with a significant increase of FEV1
      [L]-preFEV1: 1.0 +/- 0.4, post-FEV1: 1.2 +/- 0.5; p < 0.001. A trend for reduced
      right ventricle systolic pressure (RVSP) [mm Hg]: pre-treatment: 44.5 +/- 12.9;
      post-treatment: 36.3 +/- 14.3; p = 0.068 and ET-1 [fmol/ml]: pre-treatment: 1.7
      +/- 2.8; post-treatment: 1.3 +/- 1.9; p = 0.076, but not for NT-proBNP was
      noticed. Improvement of both, 6MWT [m]: pre-treatment: 294 +/- 132; post
      treatment: 415 +/- 102; p < 0.001 and MRC [pts.]: pre-treatment: 3.3 +/- 0.8;
      post-treatment: 1.8 +/- 0.9; p < 0.001, were noticed. 6MWT correlated with RV%TLC
      (p < 0.05; r = -0.46; r = -0.53; respectively) and FEV1 (p < 0.05; r = 0.55; r =
      0.60, respectively) on admission as well as on discharge. There was no such
      correlation with RVSP or PAPmean. CONCLUSIONS: Pulmonary hyperinflation and
      bronchial obstruction may be reduced by effective COPD exacerbation treatment and
      are accompanied by clinical improvement. The mPAP reduction observed in the
      course of treatment was not correlated with the results of 6MWT and MRC score.

PMID- 25577532
TI  - Bird fancier's lung: clinical-radiological presentation in 15 cases.
AB  - INTRODUCTION: Bird fancier's lung (BFL) is a type of hypersensitivity pneumonitis
      occurring in response to avian antigens (usually inhaled proteins in bird
      feathers and droppings). The diagnosis is based on a combination of clinical,
      radiological, and biopsy characteristics. The present study was planned to
      highlight the clinico-radiological presentation in cases of BFL. MATERIAL AND
      METHODS: The present study is a retrospective analysis of cases of bird fancier's
      lung diagnosed in a unit of Vallabhbhai Patel Chest Institute over a period of
      two years, from 2013-2014. The clinico-radiological features of the subjects were
      analysed. The diagnosis of BFL was made as per criteria laid down by Mark
      Schuyler and Yvon Cormier. RESULTS: There were a total of fifteen cases diagnosed
      with BFL during the study period, comprising twelve females and three males with
      a mean age of 54.93 +/- 14.21 years. All the studied subjects gave significant
      history of exposure to pigeons and were non-smokers. The period of symptoms prior
      to presentation varied from one to eight years. The main symptoms on presentation
      were exertional breathlessness and cough. Radiologically, diffuse centrilobular
      nodules, ground glassing - diffuse or patchy predominant in upper lobes, fibrosis
      with or without traction bronchiectasis, honeycombing, and mediastinal
      lymphadenopathy were seen. Bronchoscopy showed ill-defined granulomas and chronic
      interstitial inflammation. CONCLUSIONS: BFL can exhibit a wide range of
      radiological patterns, and a high index of suspicion must be maintained, with
      particular attention to detailed exposure history in every case of interstitial
      lung disease.

PMID- 25577533
TI  - [Primary pulmonary mucosa-associated lymphoid tissue lymphoma: a case report].
AB  - Primary pulmonary lymphoma accounts only 0,5% of all primary lung neoplasms.
      Mucosa-associated lymphoid tissue (MALT) lymphoma is a low grade B-cell
      extranodal lymphoma. It is a quite infrequent entity, however it constitutes from
      72% to 90% of all pulmonary lung lymphomas. Long-term stimulation of bronchus
      associated lymphoid tissue by antigens, smoking, inflammatory disorders or
      autoimmune diseases are thought to be leading to the development of MALT
      lymphoma. We present the case of primary pulmonary mucosa-associated lymphoid
      tissue lymphoma. A 76-year-old man with a history of heavy smoking (22.5 pack
      years) was admitted to the hospital for a further diagnostics of an abnormal
      finding in the right lung visualized on the chest X-ray. The diagnostic process,
      including imagining studies did not reveal the etiology of a lesion in the right
      lung. The patient was qualified for surgical diagnostics. The histological
      finding confirmed extranodal marginal low-grade B-cell lymphoma of mucosa 
      associated lymphoid tissue. 

PMID- 25577534
TI  - Leflunomide-induced acute interstitial pneumonia in a patient treated for
      rheumatoid arthritis.
AB  - Leflunomide is a disease-modifying anti-rheumatic drug that is used in patients
      with rheumatoid arthritis (RA), who do not respond well to standard RA treatment.
      Leflunomide therapy may, however, be related with significant pulmonary
      complications in predisposed individuals. We present a patient with RA treated
      with leflunomide, in whom leflunomide lung injury had a fatal outcome. Potential
      risk factors for pulmonary complications of leflunomide treatment and the
      management of patients with leflunomide lung injury are discussed. 

PMID- 25577535
TI  - [Vascular ring: a rare cause of dyspnea in an elderly male patient. Case report].
AB  - Shortness of breath (dyspnea) and changes present in X-rays of the chest are most
      frequent symptoms indicating further pulmonary diagnostic. Presented is the case
      of 71-year-old patient reffered from general practitioner due to exacerbation of
      dyspnea and abnormalities present in the chest X-ray.The patient has been treated
      for ischemic heart disease and arrythmia for a couple of years.Three-dimensional
      CT of the chest revealed a vascular ring of aorta.It is a defect characterized by
      a faulty flow of large vascular trunks, which built a cardiovascular ring that
      partially or completely enricle the structure of mediastinum (esophagus,
      trachea).The observed clinical symptoms are a result of pressure applied to the
      structure of the mediastinum and its intensity. This cardiovascular defect is
      diagnosed during early stages of childchood development and for it to be
      recognized in an adult patient is a casuistic case. 

PMID- 25577536
TI  - [Diagnostic and therapeutic difficulties in mediastinal fibromatosis. Case
      report].
AB  - Mediastinal fibromatosis is a very rare mesenchymal tumor originated from fibrous
      tissue. A case of 26-year old men with mediastinal tumor causes respiratory
      insufficiency and dysphagia is described. This sympthoms occured due to
      esophageal impression and infiltration with occlusion of main left bronchus by
      mediastinal tumor. Ethiology of the tumor was established based on histopathology
      assesment of the tissue samples taken during explorative thoracotomy after 3
      years and many other diagnostic procedures undertaken. The authors describe
      difficulties in diagnosis of mediastinal tumors, especially those rare observed. 

PMID- 25577537
TI  - [Application of basophil activation test in diagnosing aspirin hypersensitivity].
AB  - In the face of increasing prevalence of hypersensitivity reactions, introduction
      of effective, reliable and safe methods plays a crucial role in their diagnosing.
      Among the currently available laboratory (in vitro) methods is basophil
      activation test (BAT). It is a flow- cytometry based assay that allows to
      identificate in the blood sample basophils and additionally to asses the degree
      of cell activation after exposure to an antigen. The most common superficial
      identification markers are CD63 and CD203c, which increase in number after
      activation. Basophil actvation test can be applied to confirm diagnosis of
      allergy to Hymenoptera venoms, food, pollens and hypersensitivity to drugs. The
      aim of present paper is to present theoretical methods of this test as well as
      its pros and cons. We focus also on presentation of clinical case where BAT
      seemed to be a necessary addition to a routine diagnostic pathway. We present a
      case of identification of the culprit drug which caused an anaphylactic reaction.

PMID- 25577538
TI  - [Assessment of respiratory function in the qualification for lung cancer
      surgery].
AB  - Surgery is the treatment of choice in patients with a diagnosis of non-small cell
      lung cancer (NSCLC). A pivotal of eligibility for resection is the early stage of
      the disease and histopathological assessment. The performance status and
      comorbidities in population, predominated by elderly patients, also influence the
      therapeutic decisions. In some lung cancer patients COPD coexists, characterized
      by a decrease in lung function. Then the preoperative evaluation is particularly
      important, for both the risk of postoperative complications, lung function and
      quality of life postoperatively. Recently several recommendations for
      preoperative evaluation of patients being considered for surgery were published.
      The guidelines of BTS (2001, 2010), ACCP (2007, 2013) and joint recommendations
      of ERS and ESTS (2009) have been based on the currently available research
      results, and indicated the algorithms. The recommendations ERS/ESTS and ACCP
      distinguished cardiac risk estimation in all patients, which should precede the
      evaluation of lung function. According to the latest recommendations (ACCP 2013)
      the next step is spirometry, DLCO measurement and calculation of predicted
      postoperative values for both parameters. The low-technology exercise tests
      (stair climbing, shuttle walk test) were assigned as valuable to discriminate
      patients at low and intermediate perioperative risk. The cardiopulmonary exercise
      test (CPET) is recommended to be performed at the final qualification for surgery
      in patients with high risk. It was also stressed that therapeutic decisions
      should be taken multidisciplinary, allowing to estimate the risk of complications
      and to evaluate the expected quality of life in the postoperative time. 

PMID- 25577539
TI  - [New dry powder inhalers].
AB  - The most recently approved DPI's - ElliptaTM and NEXThaler(r) are the most modern
      inhalers on the market. Both are flow independent in the physiological range of
      flows seen in patients with asthma and/or COPD. Both require three actions (open
      load -inhaler) for a successful inhalation. The ElliptaTM inhaler is the first
      DPI, which enables simultaneous delivery of two compounds without need for co
      formulation. NEXThaler(r) is the only DPI on the market delivering extra fine
      aerosol (MMAD < 2 MUm) of a combined inhalation product of inhaled corticosteroid
      and long-action b2-agonist. Both have been approved world wide for products used
      in treatment of asthma and COPD. 

PMID- 25577541
TI  - Cadaver study of the topography of the musculotendinous junction of the finger
      extensor muscles: applicability to tendon rupture following closed wrist trauma.
AB  - Rupture of the extensor pollicis longus (EPL) tendon in the wrist is a delayed
      complication that can occur after wrist injury. Several etiology-related
      hypotheses have been made to explain these ruptures. The one most commonly
      accepted is necrosis at the musculotendinous junction of the EPL, which is
      compressed between the extensor retinaculum and dorsal aspect of the radius. To
      confirm this hypothesis, we performed an anatomical study to show the close
      relationship between the extensor retinaculum and the musculotendinous junction
      of the EPL muscle. We calculated the distance between the musculotendinous
      junction of the various finger extensor muscles and the proximal edge of the
      extensor retinaculum. We were able to show that this junction is located under
      the extensor retinaculum for the extensor indicis (EI) and EPL muscles, but the
      latter is in the third extensor compartment, which is a tight, confined space.
      Any pressure increase in this space following trauma, for example, can bring
      about compartment syndrome at this musculotendinous junction, which some authors
      have found to be poorly vascularized. 

PMID- 25577540
TI  - A stable human-cell system overexpressing cystic fibrosis transmembrane
      conductance regulator recombinant protein at the cell surface.
AB  - Recent human clinical trials results demonstrated successful treatment for
      certain genetic forms of cystic fibrosis (CF). To extend treatment opportunities
      to those afflicted with other genetic forms of CF disease, structural and
      biophysical characterization of CF transmembrane conductance regulator (CFTR) is
      urgently needed. In this study, CFTR was modified with various tags, including a
      His10 purification tag, the SUMOstar (SUMO*) domain, an extracellular FLAG
      epitope, and an enhanced green fluorescent protein (EGFP), each alone or in
      various combinations. Expressed in HEK293 cells, recombinant CFTR proteins
      underwent complex glycosylation, compartmentalized with the plasma membrane, and
      exhibited regulated chloride-channel activity with only modest alterations in
      channel conductance and gating kinetics. Surface CFTR expression level was
      enhanced by the presence of SUMO* on the N-terminus. Quantitative mass
      spectrometric analysis indicated approximately 10% of the total recombinant CFTR
      (SUMO*-CFTR(FLAG)-EGFP) localized to the plasma membrane. Trial purification
      using dodecylmaltoside for membrane protein extraction reproducibly recovered 178
      +/- 56 MUg SUMO*-CFTR(FLAG)-EGFP per billion cells at 80% purity. Fluorescence
      size-exclusion chromatography indicated purified CFTR was monodisperse. These
      findings demonstrate a stable mammalian cell expression system capable of
      producing human CFTR of sufficient quality and quantity to augment future CF drug
      discovery efforts, including biophysical and structural studies.

PMID- 25577542
TI  - The shortened infusion time of intravenous ibuprofen part 1: a multicenter, open
      label, surveillance trial to evaluate safety and efficacy.
AB  - PURPOSE: The main purpose of the study was to determine the safety profile and
      efficacy of intravenous ibuprofen administered over 5 to 10 minutes for the
      treatment of pain or fever in hospitalized patients. Current evidence supports
      the use of intravenous infusions of ibuprofen to control pain and reduce the
      opioid requirements associated with surgical pain. Current dosing guidelines
      recommend that the drug be administered over 30 minutes. However, a more rapid
      infusion might yield additional benefits. The safety profile and efficacy of a
      shortened infusion time requires additional study. METHODS: This was a Phase IV
      multicenter, open-label, surveillance clinical study. Thirteen clinical centers
      located in the United States enrolled a total of 150 adult hospitalized patients
      with pain or fever. Patients experiencing pain received 800 mg intravenous
      ibuprofen infused over 5 to 10 minutes every 6 hours for up to 24 hours (4 doses)
      and patients experiencing fever received 400 mg intravenous ibuprofen infused
      over 5 to 10 minutes every 4 hours for up to 24 hours (6 doses). Vital signs,
      adverse events, and pain scores were assessed. The exclusion criteria included
      inadequate intravenous access; patients younger than 18 years of age; history of
      allergy or hypersensitivity to any component of intravenous ibuprofen, aspirin,
      or other nonsteroid anti-inflammatory drugs; active hemorrhage or clinically
      significant bleeding; pregnancy or nursing; and patients in the perioperative
      period in the setting of coronary artery bypass graft surgery. FINDINGS: Adverse
      events were reported for 43 of 150 patients (29%). The most common adverse events
      experienced by patients were infusion site pain in 22 of 150 patients (15%) and
      flatulence (8 of 150 [5%]). Four patients (3%) discontinued the study drug due to
      infusion-site pain. In the patients experiencing fever, temperature decreased
      from baseline over 4 hours (mean [SD] reduction of 1.5 [1.25] degrees F). In
      patients experiencing pain, patient-reported visual analog scale scores decreased
      from baseline over 4 hours (mean [SD] reduction of 27.1 [31.29] mm).
      IMPLICATIONS: The study demonstrates that more rapid administration of
      intravenous ibuprofen is well tolerated and supports intravenous ibuprofen as an
      effective treatment for pain and fever in hospitalized patients.

PMID- 25577543
TI  - Assessment of montelukast, doxofylline, and tiotropium with budesonide for the
      treatment of asthma: which is the best among the second-line treatment? A
      randomized trial.
AB  - PURPOSE: Data comparing various second-line treatments for asthma with subjective
      and objective assessment are lacking. This study aimed to compare the efficacy
      and safety of montelukast, doxofylline, and tiotropium with a low-dose budesonide
      in patients with mild to moderate persistent asthma. METHODS: Patients, all of
      whom were concurrently using inhaled budesonide (400 ug), were treated for 6
      months with formoterol (12 ug), montelukast (10 mg), doxofylline (400 mg), or
      tiotropium (18 ug). Outcomes included forced expiratory volume in 1 second
      (FEV1), Saint George Respiratory Questionnaire (SGRQ) scores, asthma symptom
      scores (daytime and nighttime), and assessment of tolerability and rescue
      medication use. FINDINGS: A total of 297 patients completed the study. In all 4
      groups, significant improvements were observed in all the outcome measures, with
      formoterol treatment having greater and earlier improvements than the other 3
      second-line controller medications with budesonide. Among the second-line
      treatments, monteradlukast improved the FEV1 from day 45 (P < 0.01), SGRQ scores
      from day 30 (P < 0.0001), daytime scores from day 30 (P < 0.05), nighttime scores
      from day 30 (P < 0.0001), and rescue medication use from day 15 (P < .0001) at a
      faster rate than doxofylline or tiotropium with budesonide. No patients
      discontinued the treatment because of adverse reactions. IMPLICATIONS: Among the
      tested second-line treatment regimens, the budesonide/montelukast combination was
      found to be superior to either the budesonide/doxofylline or
      budesonide/tiotropium combination in all the outcome measures without adversely
      affecting the tolerability of the patients. Further clinical studies with
      blinding techniques are likely to be useful.

PMID- 25577544
TI  - Electrical stunning effectiveness with current levels lower than 1 A in lambs and
      kid goats.
AB  - An experiment with 360 lambs grouped into three Spanish commercial categories,
      (Pascual, 13-16 kg; Recental, 9-13 kg and Lechal <7 kg carcass weight) and kid
      goats (7 kg) was performed to assess stunning effectiveness after head-only (HO)
      and head-to-body (HB) electrical stunning with intensity currents of 0.3, 0.5 and
      0.7 Amperes (A) compared to 1.0 A. After stunning, all animals showed tonic
      clonic muscular activity and epileptiform EEG, absence of rhythmic breathing,
      corneal reflex, spontaneous blinking and pain sensibility. The quiescent EEG
      occurred earlier (P < 0.05) in HB compared to HO in all categories. More animals
      recovered corneal reflex and rhythmic breathing before onset of the quiescent
      activity after HO (from 15 to 50%) compared to HB (from 0 to 15%) (P < 0.05).
      Concluding, HO and HB electrical stunning with 0.3, 0.5 and 0.7 A induce
      effective stunning similar to 1.0 A in lambs and kid goats. After stunning and
      sticking, brain failure occurs earlier in HB than HO system.

PMID- 25577545
TI  - Serum cortisol concentration in horses with heaves treated with fluticasone
      proprionate over a 1 year period.
AB  - The purpose of this study is to measure the effect of long-term administration of
      inhaled fluticasone proprionate on cortisol concentrations in heaves-affected
      horses. Eleven horses with heaves were treated with fluticasone at least once
      daily at dosages required to improve lung function or with antigen avoidance
      alone for 1 year. Morning serum cortisol was measured before and after 10, 30,
      110, 190, 230, 280, and 320 days of treatment. Cortisol was also measured in the
      afternoon of day 330. Cortisol was significantly lower in the Fluticasone group
      on days 30, 110, and 190 when compared with the Antigen avoidance group. Cortisol
      measured on day 330 was also significantly lower in the Fluticasone group.
      Results indicate that inhaled fluticasone, when administered at therapeutic
      dosages, can significantly suppress serum cortisol concentrations for 8-24 h. The
      clinical significance of this finding remains to be ascertained, as no clinical
      signs were associated with this cortisol suppression. 

PMID- 25577546
TI  - Modeling of TRPV4-C1 -mediated calcium signaling in vascular endothelial cells
      induced by fluid shear stress and ATP.
AB  - The calcium signaling plays a vital role in flow-dependent vascular endothelial
      cell (VEC) physiology. Variations in fluid shear stress and ATP concentration in
      blood vessels can activate dynamic responses of cytosolic-free [Formula: see
      text] through various calcium channels on the plasma membrane. In this paper, a
      novel dynamic model has been proposed for transient receptor potential vanilloid
      4 [Formula: see text]-mediated intracellular calcium dynamics in VECs induced by
      fluid shear stress and ATP. Our model includes [Formula: see text] signaling
      pathways through P2Y receptors and [Formula: see text] channels (indirect
      mechanism) and captures the roles of the [Formula: see text] compound channels in
      VEC [Formula: see text] signaling in response to fluid shear stress (direct
      mechanism). In particular, it takes into account that the [Formula: see text]
      compound channels are regulated by intracellular [Formula: see text] and
      [Formula: see text] concentrations. The simulation studies have demonstrated that
      the dynamic responses of calcium concentration produced by the proposed model
      correlate well with the existing experimental observations. We also conclude from
      the simulation studies that endogenously released ATP may play an insignificant
      role in the process of intracellular [Formula: see text] response to shear
      stress.

PMID- 25577547
TI  - How pharmacist-patient communication determines pharmacy loyalty? Modeling
      relevant factors.
AB  - BACKGROUND: Portuguese community pharmacies provide pharmaceutical services, such
      as therapeutic outcomes follow-up, supplemented by relevant point-of-care testing
      that require continuity of provision to be effective. OBJECTIVES: To identify
      factors of technical and communication nature that during a patient interview
      contribute to patients' loyalty. METHODS: A cross-sectional descriptive study,
      with a purposive sample of community pharmacies providing pharmaceutical care,
      was conducted. Patient interviews were taped and transcribed verbatim. Duration,
      segments and utterances were identified and time stamped, using a previously
      validated coding scheme. To identify predictors of loyalty, logistic regression
      analyses were performed. RESULTS: From 59 interviews, participants' average age
      was 65.7 years and 42 (71.2%) were female; 45 (76.3%) interviews were classified
      as outcomes measurements and 14 (23.7%) as pharmaceutical consultations, with
      33.2% of the patients booking a following appointment. The significant items to
      explain loyalty were associated with lifestyle and psychosocial exchange, age of
      the patient, and the presence of all interview segments (i.e. a complete
      consultation). CONCLUSION: Contrary to common professional beliefs and practice
      orientation it would appear that pharmacists' technical skills are not the
      essential factors that promote patients' loyalty needed for continuity of care,
      at least in the same extent as the social and lifestyle-related content of the
      exchange. Pharmaceutical care education should focus on relational skills as much
      as on medication-related competencies.

PMID- 25577548
TI  - Biomechanical comparison of an interspinous fusion device and bilateral pedicle
      screw system as additional fixation for lateral lumbar interbody fusion.
AB  - BACKGROUND: This investigation compares an interspinous fusion device with
      posterior pedicle screw system in a lateral lumbar interbody lumbar fusion.
      METHODS: We biomechanically tested six cadaveric lumbar segments (L1-L2) under an
      axial preload of 50N and torque of 5Nm in flexion-extension, lateral bending and
      axial rotation directions. We quantified range of motion, neutral zone/elastic
      zone stiffness in the following conditions: intact, lateral discectomy, lateral
      cage, cage with interspinous fusion, and cage with pedicle screws. FINDINGS: A
      complete lateral discectomy and annulectomy increased motion in all directions
      compared to all other conditions. The lateral cage reduced motion in lateral
      bending and flexion/extension with respect to the intact and discectomy
      conditions, but had minimal effect on extension stiffness. Posterior
      instrumentation reduced motion, excluding interspinous augmentation in axial
      rotation with respect to the cage condition. Interspinous fusion significantly
      increased flexion and extension stiffness, while pedicle screws increased
      flexion/extension and lateral bending stiffness, with respect to the cage
      condition. Both posterior augmentations performed equivalently throughout the
      tests except in lateral bending stiffness where pedicle screws were stiffer in
      the neutral zone. INTERPRETATION: A lateral discectomy and annulectomy generates
      immediate instability. Stand-alone lateral cages restore a limited amount of
      immediate stability, but posterior supplemental fixation increases stability.
      Both augmentations are similar in a single level lateral fusion in-vitro model,
      but pedicle screws are more equipped for coronal stability. An interspinous
      fusion is a less invasive alternative than pedicle screws and is potentially a
      conservative option for various interbody cage scenarios.

PMID- 25577549
TI  - [Pulmonary arterial hypertension associated to human immunodeficiency virus].
AB  - From the advent of the highly effective antiretroviral treatment, the life
      expectancy of patients with human immunodeficiency virus has increased
      significantly. At present, the causes of death are non-infectious complications.
      Between them, the pulmonary arterial hypertension has a special importance. It is
      important early detection to establish the therapeutic, with the objective of
      preventing a fatal outcome to future. 

PMID- 25577550
TI  - [Subvalvular pannus as cause of late mismatch after aortic valve replacement].

PMID- 25577551
TI  - [Obstructive sleep apnea syndrome and ischemic heart disease. Evidence of their
      relationship].
AB  - The purpose of this review is to analyse the relation between obstructive sleep
      apnea and coronary disease. We present epidemiological data on the respiratory
      disorder and its association with ischemic cardiopathy, as well as common
      cardiovascular risk factors, physiopathological interactions between both
      conditions, clinical evolution and impact of treatment on prognosis. 

PMID- 25577552
TI  - Expression of carbonic anhydrase 9 is a novel prognostic marker in resectable
      hepatocellular carcinoma.
AB  - Carbonic anhydrase 9 (CA9), which regulates cellular proliferation and the acid
      base balance, is known as prognostic factor in various types of cancer. The aim
      of this study is to investigate the clinical implications of CA9 expression in
      patients with hepatocellular carcinoma. Immunohistochemical staining for CA9 was
      performed on tissue microarrays of hepatocellular carcinoma and paired non
      neoplastic liver tissue from a training cohort of 838 patients and a validation
      cohort of 225 patients. Membranous staining in more than 5 % of the tumor cells
      was considered to indicate CA9 positivity. The prognostic value of CA9 expression
      was statistically evaluated. In the training cohort, CA9 positivity (181 cases,
      21.5 %) was significantly correlated with shorter overall survival (OS; p <
      0.001) and recurrence-free survival (RFS; p = 0.004). In multivariate analysis,
      CA9 positivity was independently associated with reduced OS (p = 0.023), but not
      significantly associated with RFS (p = 0.384). These results were validated in an
      additional cohort (CA9 positivity in 35 cases, 15.6 %; OS, p = 0.015; RFS, p =
      0.979). Pooled cohort analysis showed that this predictor was independently
      associated with higher mortality (OS; p < 0.001). These data indicate that CA9
      expression is a poor prognostic factor in resectable hepatocellular carcinoma
      (HCC) patients.

PMID- 25577553
TI  - Usefulness of CA125 in the differential diagnosis of uterine adenomyosis and
      myoma.
AB  - OBJECTIVES: To evaluate the usefulness of CA125 levels in the differential
      diagnosis of adenomyosis and myoma. This has been addressed by few, if any,
      previous studies. STUDY DESIGN: Preoperative serum CA125 levels were measured in
      2149 women who were diagnosed at total hysterectomy as having adenomyosis, myoma,
      endometriosis, and/or normal pelvis. Their medical records were retrieved and
      reviewed. RESULTS: The mean serum CA125 level in the adenomyosis patients was
      significantly greater than that in the patients diagnosed with myoma (65.21+/
      96.60 U/mL vs.12.86+/-14.23 U/mL, respectively; P<0.001). In the differential
      diagnosis of adenomyosis and myoma, the cut-off serum CA125 level with the
      highest accuracy (78.8%) and highest diagnostic value (61.2%) was 19 U/mL. Using
      this cut-off value, the negative predictive value was 69.5%, and the positive
      predictive value was 76.5%. These results are clearly superior to those of the
      empirical single cut-off value of 35 U/mL. Receiver operating characteristic
      curve analysis revealed the area under the curve for differentiating adenomyosis
      from myoma was 0.776, indicating good diagnostic performance. CONCLUSION: In the
      differential diagnosis of adenomyosis and myoma, cut-off values for CA125,
      particularly the cut-off value of 19 U/mL, provide improved diagnostic
      performance. Serum CA125 testing can be performed during the initial screening of
      women with possible adenomyosis to differentiate this condition from myoma,
      although the diagnostic accuracy of using CA125 testing alone is limited.

PMID- 25577554
TI  - Cathepsin B in human myometrium and in uterine leiomyomas at various stages of
      tumour growth.
AB  - OBJECTIVE: Cathepsin B is a major cysteine protease involved in the degradation
      of extracellular matrix proteins, as well as in the activation of precursor forms
      of other proteases and in release of matrix-bound growth factors. We assessed the
      expression and activity of cathepsin B, and the inhibitory effect of cysteine
      protease inhibitors in human myometrium and uterine leiomyomas at various stages
      of tumour growth. STUDY DESIGN: Studies were performed on human myometrium
      collected from 12 patients and on uterine leiomyomas of various weights: small
      (less than or equal to 25 g, taken from 10 patients) and large (more than or
      equal to 100 g, obtained from 13 patients). Tissue extracts were assayed for
      cathepsin B activity and for inhibitory effect of cysteine protease inhibitors
      against papain using fluorogenic substrates, and calculated per DNA content.
      Statistical analysis was performed by Kruskal-Wallis analysis of variance
      followed by Dunn's post hoc tests. The enzyme expression was evaluated by
      SDS/polyacrylamide gel electrophoresis followed by Western immunoblotting.
      RESULTS: In all the investigated tissues cathepsin B exists mainly in a fully
      processed double-chain form. The enzyme activity and expression were similar in
      control myometrium and in small leiomyomas. However, they distinctly increased
      during tumour growth. The effect of cysteine protease inhibitors was comparable
      in all the tissues examined. CONCLUSION: These data suggest that the enhanced
      activity and expression of cathepsin B but not the action of cysteine protease
      inhibitors contribute to an increased remodelling of extracellular matrix and
      bioavailability of various growth factors, which favour leiomyoma growth.

PMID- 25577555
TI  - Has there been a change in peripartal maternal mortality in a tertiary care
      obstetric European center over the last five decades?
AB  - OBJECTIVE: Maternal mortality still remains a significant problem in obstetrics
      worldwide. Unchanged or even rising maternal mortality has been reported in
      several countries. The present study analyzed whether the pattern of maternal
      mortality has changed over the last five decades at the Department of Obstetrics
      and Gynecology of the Medical University of Graz. STUDY DESIGN: Starting in 1981,
      a registry of maternal deaths was established and regularly updated at our
      institution based on retrospective data. Between 1963 and 2012, a total of
      187,917 women delivered. Thirty-five consecutive maternal deaths were observed
      and subdivided into 10 year cohorts. METHODS: The registry of maternal deaths
      included deliveries after 28+0 weeks of gestation. Puerperal deaths were defined
      as deaths up to day 42 post partum. MAIN OUTCOME MEASURES: Clinical data from
      maternal deaths were extracted from hospital records and autopsy reports.
      RESULTS: Maternal mortality rates declined from 35.0, 29.0, 2.4, 13.1 to 3.6 per
      100,000 deliveries in the five subsequent periods, respectively. Sixty-six
      percent of women who died were 30 years or older. The cesarean section rate was
      49%. Ninety-one percent of the 35 maternal deaths occurred in women with no
      significant medical history or risk factors. Seventy-five percent of deaths
      occurred after the 37+0 weeks of gestation. During all study periods, the
      prevalence of infections and hemorrhage was highest. The main causes of bleeding
      were uterine rupture and placental abruption, respectively. CONCLUSION: Even
      nowadays, peripartal maternal deaths occur mainly due to infections and
      hemorrhage and also in women with no significant medical history.

PMID- 25577556
TI  - Which approach is best for subungual glomus tumors? Transungual with
      microsurgical dissection of the nail bed or periungual?
AB  - Glomus tumors are rare, accounting for 1% to 5% of all hand tumors. The treatment
      of subungual glomus tumors consists of complete surgical excision, either by the
      periungual or transungual approach. Tumor recurrence and nail dystrophy are the
      main complications. The purpose of this study was to evaluate the outcome as a
      function of the surgical approach used - transungual or periungual. Fifty-three
      patients presenting with a subungual glomus tumor underwent surgical excision
      through the periungual approach if the tumor was peripheral, or the transungual
      approach if the tumor was centrally located. These patients were followed for an
      average of 2years. Pain relief was always obtained the day following surgery.
      Wound healing was achieved on average after 2weeks with the periungual approach
      and 5weeks with the transungual approach. Other than some longitudinal striations
      in 10 patients (18.9%) who had been operated through the transungual approach,
      there were no complications or tumor recurrence. We recommend a periungual
      approach for a peripheral tumor and a transungual approach for a central tumor.
      The latter approach, which carries some risks of nail-related sequelae--always
      minor in our experience--allows for better exposure if the tumor is centrally
      located.

PMID- 25577558
TI  - Foreword. 55th Symposium issue.

PMID- 25577557
TI  - [Barriers to ART initiation in HIV infected subjects and with treatment
      indication in Spain. Why don't they start their treatment? Bridgap Study].
AB  - INTRODUCTION: In Spain, HIV treatment guidelines are well known and generally
      followed. However, in some patients there are no plans to initiate ART despite
      having treatment indications. The current barriers to ART initiation are
      presented. METHODS: A cross-sectional survey including every HIV infected patient
      in care in 19 hospitals across Spain in 2012, with >=1 indication to start ART
      according to 2011 national treatment guidelines, who had not been scheduled for
      ART initiation. Reasons for deferring treatment were categorized as follows (non
      exclusive categories): a) The physician thinks the indication is not absolute and
      prefers to defer it; b) The patient does not want to start it; c) The physician
      thinks ART must be started, but there is some limitation to starting it, and d)
      The patient has undetectable viral load in absence of ART. RESULTS: A total of
      256 patients, out of 784 originally planned, were included. The large majority
      (84%) were male, median age 39 years, 57% MSM, 24% heterosexuals, and 16% IDUs.
      Median time since HIV diagnosis was 3 years, median CD4 count, 501 cells/mm3,
      median viral load 4.4 log copies/ml. Main ART indications were: CD4 count <500
      cells/mm(3), 48%; having an uninfected sexual partner, 28%, and hepatitis C
      coinfection, 23%. Barriers due to, the physician, 55%; the patient, 28%; other
      limitations, 23%; and undetectable viral load, 6%. CONCLUSIONS: The majority of
      subjects with ART indication were on it. The most frequent barriers among those
      who did not receive it were physician-related, suggesting that the relevance of
      the conditions that indicate ART may need reinforcing.

PMID- 25577559
TI  - Data-driven shape parameterization for segmentation of the right ventricle from
      3D+t echocardiography.
AB  - Model-based segmentation facilitates the accurate measurement of geometric
      properties of anatomy from ultrasound images. Regularization of the model surface
      is typically necessary due to the presence of noisy and incomplete boundaries.
      When simple regularizers are insufficient, linear basis shape models have been
      shown to be effective. However, for problems such as right ventricle (RV)
      segmentation from 3D+t echocardiography, where dense consistent landmarks and
      complete boundaries are absent, acquiring accurate training surfaces in dense
      correspondence is difficult. As a solution, this paper presents a framework which
      performs joint segmentation of multiple 3D+t sequences while simultaneously
      optimizing an underlying linear basis shape model. In particular, the RV is
      represented as an explicit continuous surface, and segmentation of all frames is
      formulated as a single continuous energy minimization problem. Shape information
      is automatically shared between frames, missing boundaries are implicitly
      handled, and only coarse surface initializations are necessary. The framework is
      demonstrated to successfully segment both multiple-view and multiple-subject
      collections of 3D+t echocardiography sequences, and the results confirm that the
      linear basis shape model is an effective model constraint. Furthermore, the
      framework is shown to achieve smaller segmentation errors than a state-of-art
      commercial semi-automatic RV segmentation package. 

PMID- 25577561
TI  - Workplace safety and health for the veterinary health care team.
AB  - Veterinary clinic employers have a legal and ethical responsibility to provide a
      safe and healthy workplace. Clinic members are responsible for consistently using
      safe practices and procedures set up by their employer. Development and
      implementation of a customized comprehensive workplace safety and health program
      is emphasized, including an infection control plan. Occupational safety and
      health regulations are reviewed. The hazards of sharps, animal bites and
      scratches, and drugs are discussed. Strategies to prevent or minimize adverse
      health effects and resources for training and education are provided. 

PMID- 25577560
TI  - A parent's guide to the pediatric intensive care unit.

PMID- 25577562
TI  - Exercise in heart failure patients supported with a left ventricular assist
      device.
AB  - After implantation of a continuous-flow left ventricular assist device (CF-LVAD),
      exercise capacity in heart failure patients remains reduced with peak oxygen
      uptake (peak VO2) values averaging from 11 to 20 ml/kg/min. Total cardiac output
      in CF-LVAD patients during exercise is predominantly determined by pump speed,
      the pressure difference across the pump, and in some cases ejection through the
      aortic valve. Fixed pump speed utilized in CF-LVADs may provide insufficient
      support, resulting in a moderate cardiac output increase during increased
      physical strain. Ongoing studies are evaluating whether pump speed changes in
      response to varied loading conditions may enable LVADs to provide sufficient
      support even during strenuous exercise. In the currently used devices, evidence
      suggests that focus on optimizing non-cardiac peripheral parameters is vital.
      Extra-cardiac potentially reversible factors are anemia with low oxygen-carrying
      capacity, obesity and general deconditioning with low muscle mass. In addition,
      exercise training in CF-LVAD patients can improve peak VO2. To design
      interventions to improve functional capacity in patients treated with modern
      durable LVADs, a detailed understanding of exercise physiology in a continuous
      flow circulatory system is necessary. In this review we address the different
      components of exercise physiology in LVAD patients and point out potential
      solutions or areas of future research. 

PMID- 25577563
TI  - Pulmonary hypertension in heart failure with preserved ejection fraction.
AB  - In heart failure with preserved ejection fraction (HFpEF), an entity that remains
      challenging and difficult to treat, the development of pulmonary hypertension
      (PH), via an increase in left atrial pressure, is the direct consequence of
      reduced relaxation and enhanced stiffness of the left ventricle and is now viewed
      as an important contributor to clinical worsening and increased mortality. PH
      becomes a relevant clinical phenotype in approximately 50% of patients with HFpEF
      and represents a true challenge in the clinical follow-up and management of these
      patients. Along with these epidemiologic insights, there has been increasing
      recognition of the pathophysiology of PH and its consequences on the right
      ventricle in patients with HFpEF. Novel and effective therapeutic interventions
      aimed at preventing and reversing PH are highly relevant in the attempt to modify
      the poor clinical trajectory and growing health care burden of HFpEF. Many
      theoretical rationales as well as progressively accumulating evidence support the
      usefulness of nitric oxide pathway-potentiating compounds in targeting the lung
      vasculature through phosphodiesterase 5 inhibitors or guanylate cyclase
      stimulators to produce vasodilation and potentially a biologic effect. These
      pharmacologic strategies may be clinically effective options for the treatment of
      PH in patients with HFpEF; however, large controlled trials are necessary to
      address definitively the safety, tolerability, and potential impact on morbidity
      and mortality. This review details the pathophysiologic process, prevalence, and
      consequences of HFpEF-associated PH and discusses current and emerging treatment
      strategies to prevent or treat this deleterious sequela when present. 

PMID- 25577564
TI  - Restrictive chronic lung allograft dysfunction: Where are we now?
AB  - Chronic lung allograft dysfunction (CLAD) remains a frequent and troublesome
      complication after lung transplantation. Apart from bronchiolitis obliterans
      syndrome (BOS), a restrictive phenotype of CLAD (rCLAD) has recently been
      recognized, which occurs in approximately 30% of CLAD patients. The main
      characteristics of rCLAD include a restrictive pulmonary function pattern with a
      persistent decline in lung function (FEV1, FVC and TLC), persistent parenchymal
      infiltrates and (sub)pleural thickening on chest CT scan, as well as
      pleuroparenchymal fibroelastosis and obliterative bronchiolitis on
      histopathologic examination. Once diagnosed, median survival is only 6 to 18
      months compared with 3 to 5 years with BOS. In this perspective we review the
      historic evidence for rCLAD and describe the different diagnostic criteria and
      prognosis. Furthermore, we elaborate on the typical radiologic and
      histopathologic presentations of rCLAD and highlight risk factors and mechanisms.
      Last, we summarize some opportunities for further research including the urgent
      need for adequate therapy. In this perspective we not only assess the current
      knowledge, but also clarify the existing gaps in understanding this increasingly
      recognized complication after lung transplantation. 

PMID- 25577566
TI  - Late right heart failure during support with continuous-flow left ventricular
      assist devices adversely affects post-transplant outcome.
AB  - BACKGROUND: Right heart failure (RHF) is an unresolved issue during continuous
      flow left ventricular assist device (LVAD) support. Little is known about post
      transplant outcomes in patients complicated by late RHF during LVAD support.
      METHODS: Between May 2004 and December 2013, 141 patients underwent cardiac
      transplantation after isolated LVAD bridging at our center. Late RHF was defined
      as heart failure requiring medical intervention >4 weeks after LVAD implantation.
      RESULTS: The patients' mean age was 53 +/- 13 years, 82% were men, and 36% had an
      ischemic etiology. The mean duration of LVAD support before transplantation was
      0.75 years. Late RHF developed in 21 patients (15%) during LVAD support. Of these
      patients, 11 were supported with inotropic agents at the time of transplantation.
      Patients with RHF had higher creatinine (1.6 +/- 0.88 mg/dL vs 1.3 +/- 0.67
      mg/dL, p = 0.07), higher blood urea nitrogen (32 +/- 17 mg/dL vs 24 +/- 10 mg/dL,
      p = 0.0013), higher total bilirubin (0.96 +/- 0.46 mg/dL vs 0.78 +/- 0.42 mg/dL,
      p = 0.07), and lower albumin (3.8 +/- 0.60 g/dL vs 4.1 +/- 0.46 g/dL, p = 0.0019)
      at the time of transplantation compared with patients who did not develop RHF. In
      hospital mortality was significantly higher in patients with late RHF during LVAD
      support (29% vs 6.7%, p = 0.002). Overall post-transplant survival rates were 87%
      at 1 year, 83% at 3 years, and 77% at 5 years. The 5-year post-transplant
      survival was significantly worse in patients who developed late RHF during LVAD
      support compared with survival in patients who did not develop RHF (26% vs 87%, p
      < 0.0001). CONCLUSIONS: Late RHF during LVAD support adversely affects post
      transplant survival.

PMID- 25577565
TI  - Prognostic value of acute vasodilator response in pulmonary arterial
      hypertension: beyond the "classic" responders.
AB  - BACKGROUND: A "classic" response to acute vasodilator testing (drop of >10 mm Hg
      in mean pulmonary artery pressure [mPAP] to <40 mm Hg) confers an excellent
      prognosis in patients with idiopathic pulmonary arterial hypertension (IPAH) and
      identifies candidates for treatment with calcium channel blockers (CCB). Little
      is known about vasodilator responsiveness (VR) in other types of PAH, or about
      outcomes in patients with a significant but "non-classic" decrease in mPAP. We
      hypothesized that VR occurs in non-idiopathic PAH and non-classic VR portends a
      better prognosis than no VR in PAH. METHODS: Acute VR testing with nitric oxide
      was performed on 155 consecutive patients referred for PH evaluation. Non-classic
      response was defined as decrease in mPAP >10 mm Hg to >40 mm Hg with preserved
      cardiac output. Demographics and functional status were assessed at baseline and
      the first clinic visit after VR testing, and survival was followed over time.
      RESULTS: Twenty patients (13%) displayed classic VR. Among classic responders, 12
      (60%) had IPAH and 8 (40%) had connective tissue disease-associated PAH (CTD
      PAH); however, only responders with IPAH had improved survival compared with non
      responders (p = 0.02). Thirteen patients (8%) had a non-classic VR. Non-classic
      response was not associated with improved survival compared with non-responders
      (p = 0.86). Acute change in mPAP or pulmonary vascular resistance in the entire
      cohort did not predict survival. CONCLUSIONS: Classic acute VR occurs in CTD-PAH
      as well as IPAH; however, only IPAH patients have improved outcomes. A
      significant but non-classic VR is not associated with improved survival.

PMID- 25577567
TI  - Socioeconomic Status and the Trajectory of Body Mass Index Among Older Japanese:
      A Nationwide Cohort Study of 1987-2006.
AB  - OBJECTIVES: This research analyzed the body mass index (BMI) level and rate of
      change, and their association with socioeconomic status among older Japanese
      adults. METHODS: Data came from a national sample of over 4,800 Japanese adults
      aged 60 and older at baseline, with up to 7 repeated observations over a period
      of 19 years (1987-2006). Hierarchical linear modeling was used to analyze the
      intrapersonal and interpersonal differences in BMI. RESULTS: Average BMI among
      older Japanese was 22.26 at baseline and decreased with an accelerating rate over
      time. Relative to those with less education, BMI among older Japanese with more
      education was lower and it declined linearly at a faster rate over time. In
      contrast, higher household income at baseline was associated with a higher level
      of BMI but similar rates of decline over time. Furthermore, we found no evidence
      for age variations in the SES-BMI linkage as predicted by prior investigators.
      DISCUSSION: These findings provide new insights into the complex relationship
      between socioeconomic factors and BMI, and help to inform the design of health
      policies and interventions related to weight control among older adults with
      diverse socioeconomic backgrounds.

PMID- 25577568
TI  - Comprehensive genome-wide analysis of the Aux/IAA gene family in Eucalyptus:
      evidence for the role of EgrIAA4 in wood formation.
AB  - Auxin plays a pivotal role in various plant growth and development processes,
      including vascular differentiation. The modulation of auxin responsiveness
      through the auxin perception and signaling machinery is believed to be a major
      regulatory mechanism controlling cambium activity and wood formation. To gain
      more insights into the roles of key Aux/IAA gene regulators of the auxin response
      in these processes, we identified and characterized members of the Aux/IAA family
      in the genome of Eucalyptus grandis, a tree of worldwide economic importance. We
      found that the gene family in Eucalyptus is slightly smaller than that in Populus
      and Arabidopsis, but all phylogenetic groups are represented. High-throughput
      expression profiling of different organs and tissues highlighted several Aux/IAA
      genes expressed in vascular cambium and/or developing xylem, some showing
      differential expression in response to developmental (juvenile vs. mature) and/or
      to environmental (tension stress) cues. Based on the expression profiles, we
      selected a promising candidate gene, EgrIAA4, for functional characterization. We
      showed that EgrIAA4 protein is localized in the nucleus and functions as an auxin
      responsive repressor. Overexpressing a stabilized version of EgrIAA4 in
      Arabidopsis dramatically impeded plant growth and fertility and induced auxin
      insensitive phenotypes such as inhibition of primary root elongation, lateral
      root emergence and agravitropism. Interestingly, the lignified secondary walls of
      the interfascicular fibers appeared very late, whereas those of the xylary fibers
      were virtually undetectable, suggesting that EgrIAA4 may play crucial roles in
      fiber development and secondary cell wall deposition. 

PMID- 25577569
TI  - Effectiveness of a computer module to augment the training of school staff in the
      management of students with food allergies.

PMID- 25577570
TI  - Diffuse sclerosing variant of papillary thyroid carcinoma--an update of its
      clinicopathological features and molecular biology.
AB  - Diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is an uncommon
      variant of papillary thyroid carcinoma. The aim of this review is to critically
      analyse the features of this entity. A search of the literature revealed 25
      clinicopathological studies with in-depth analysis of features of DSVPTC.
      Overall, the prevalence of DSVPTC varies from 0.7-6.6% of all papillary thyroid
      carcinoma. Higher prevalence of DSVPTC was noted in paediatric patients and in
      patients affected by irradiation. DSVPTC tends to occur more frequently in women
      and in patients in the third decade of life. Macroscopically, DSVPTC can involve
      the thyroid gland extensively without forming a dominant mass. Microscopic
      examination of DSVPTC revealed extensive fibrosis, squamous metaplasia and
      numerous psammoma bodies. The latter pathological feature can aid in the pre
      operative diagnosis of the entity by fine needle aspiration and ultrasound.
      Compared to conventional papillary thyroid carcinoma, DSVPTC had a higher
      incidence of lymph node metastases at presentation. Distant metastases were noted
      in approximately 5% of the cases. Patients with DSVPTC were recommended to be
      managed by aggressive treatment protocols. It is likely that as a result of this,
      the prognosis of the patients with DSVPTC was noted to be similar to conventional
      papillary thyroid carcinoma. Overall, cancer recurrence and cancer related
      mortality have been reported in 14% and 3%, respectively, of patients with
      DSVPTC. In immunohistochemical studies, DSVPTC showed different expression
      patterns of epithelial membrane antigen, galectin 3, cell adhesion molecules, p53
      and p63 when compared to conventional papillary thyroid carcinoma. On genetic
      analysis, the occurrence of BRAF and RAS mutations are uncommon events in DSVPTC
      and activation of RET/PTC rearrangements are common. To conclude, DSVPTC has
      different clinical, pathological and molecular profiles when compared to
      conventional papillary thyroid carcinoma. 

PMID- 25577571
TI  - MGN1703, an immunomodulator and toll-like receptor 9 (TLR-9) agonist: from bench
      to bedside.
AB  - The adaptive immune system has been the main focus of immunological strategies in
      oncology with only more recent approaches targeting innate immunity. Endosomal
      toll-like receptors (TLR-7, TLR-9) activate innate immune responses by signaling
      damage-associated molecular patterns (DAMP) from decaying tumor cells. This has
      led to the development of DNA-based TLR-9 agonists, which induce antitumor
      activity through innate and subsequent adaptive immune responses. Early clinical
      trials with CpG-ODN as TLR-9 agonists were associated with unfavorable
      tolerability and narrow clinical efficacy, leading to failure in pivotal trials.
      dSLIM, the active ingredient of MGN1703, is a DNA-based, radically different
      molecular alternative to CpG-ODN, which results in genuine antitumor
      immunomodulation. Preclinical and clinical studies of MGN1703 have confirmed that
      this TLR-9 agonist has therapeutic potential in a variety of solid tumors, while
      long-term treatment with high doses was very well tolerated. A pivotal trial of
      first-line maintenance treatment with MGN1703 in patients with metastatic
      colorectal cancer is underway.

PMID- 25577572
TI  - Congestive heart failure with vascular endothelial growth factor receptor
      tyrosine kinase inhibitors.
AB  - A systematic review and meta-analysis was conducted to determine the relative
      risk (RR) of congestive heart failure (CHF) associated with approved multi
      targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase
      inhibitors (TKI). Eligible studies included randomized trials comparing arms with
      and without an FDA-approved VEGFR TKI. Statistical analyses calculated the
      relative risk (RR) and 95% confidence intervals (CI). A total of 10,647 patients
      from 16 phase III trials and 5 phase II trials were selected. All grade CHF
      occurred in 138 of 5752 (2.39%) patients receiving VEGFR TKIs and 37 of 4895
      (0.75%) patients in the non-TKI group. High-grade CHF occurred in 17 of 1426
      (1.19%) patients receiving VEGFR TKIs and 8 of 1232 (0.65%) patients in the non
      TKI group. The RR of all grade and high-grade CHF for the TKI vs. no TKI arms was
      2.69 (p<0.001; 95% CI: 1.86 to 3.87) and 1.65 (p=0.227, 95% CI: 0.73 to 3.70),
      respectively. The RR of relatively specific TKIs (axitinib) was similar to
      relatively non-specific TKIs (sunitinib, sorafenib, vandetanib, pazopanib). 

PMID- 25577573
TI  - Prevalence, presentation and occupational risk factors of chronic venous disease
      in nurses.
AB  - OBJECTIVE: In this study involving a group of nurses employed in a number of
      different medical services with relatively well-defined working conditions, the
      presence and symptoms of chronic venous insufficiency were screened and their
      association with work burden and physical working conditions was explored.
      METHODS: Of the 294 actively employed nurses during the study period, 232 (79%)
      were recruited on the basis of their willingness for participation and fulfilment
      of the inclusion criteria. RESULTS: Among the study subjects, 62.9% had at least
      one symptom of chronic venous insufficiency, and 50.4% were found to have chronic
      venous insufficiency according to Clinical-Etiology-Anatomy-Pathophysiology
      classification criteria. A significant association was found between the diurnal
      ankle circumference difference in the left-right ankles and the mean duration of
      hospital stay. CONCLUSIONS: Our results have shown that the average duration of
      hospital stay, which is among the variables used to estimate the work burden of
      nurses, is associated with an increased frequency of the signs and symptoms of
      chronic venous insufficiency.

PMID- 25577574
TI  - Associative Recognition Memory Awareness Improved by Theta-Burst Stimulation of
      Frontopolar Cortex.
AB  - Neuroimaging and lesion studies have implicated specific prefrontal cortex
      locations in subjective memory awareness. Based on this evidence, a rostrocaudal
      organization has been proposed whereby increasingly anterior prefrontal regions
      are increasingly involved in memory awareness. We used theta-burst transcranial
      magnetic stimulation (TBS) to temporarily modulate dorsolateral versus
      frontopolar prefrontal cortex to test for distinct causal roles in memory
      awareness. In three sessions, participants received TBS bilaterally to
      frontopolar cortex, dorsolateral prefrontal cortex, or a control location prior
      to performing an associative-recognition task involving judgments of memory
      awareness. Objective memory performance (i.e., accuracy) did not differ based on
      stimulation location. In contrast, frontopolar stimulation significantly
      influenced several measures of memory awareness. During study, judgments of
      learning were more accurate such that lower ratings were given to items that were
      subsequently forgotten selectively following frontopolar TBS. Confidence ratings
      during test were also higher for correct trials following frontopolar TBS.
      Finally, trial-by-trial correspondence between overt performance and subjective
      awareness during study demonstrated a linear increase across control,
      dorsolateral, and frontopolar TBS locations, supporting a rostrocaudal hierarchy
      of prefrontal contributions to memory awareness. These findings indicate that
      frontopolar cortex contributes causally to memory awareness, which was improved
      selectively by anatomically targeted TBS. 

PMID- 25577575
TI  - Expectations of Task Demands Dissociate Working Memory and Long-Term Memory
      Systems.
AB  - Many aspects of the complex relationship between working memory (WM) and long
      term memory (LTM) remain unclear. Here, we manipulated task demands on a brief
      delayed-recognition paradigm to reveal behavioral and neural dissociations
      between these systems. Variations from a Baseline task included 3 challenges:
      increased delay duration, distraction during maintenance, and more closely
      matched memory probes, which were presented in behavioral experiments and during
      functional magnetic resonance imaging. Each of the challenges resulted in a
      significant decline in WM accuracy, and interestingly, a concurrent improvement
      in incidental LTM. Neural data revealed that, in task blocks, when participants
      anticipated, and then experienced, increased demands, they engaged medial
      temporal lobe (MTL) regions more during both the encoding and delay periods.
      Overall, these results indicate that distinct memory systems are recruited based
      on anticipated demands of a memory task, and MTL involvement underlies the
      observed dissociation between WM and LTM performance. 

PMID- 25577577
TI  - Two Types of Neurons in the Primate Globus Pallidus External Segment Play
      Distinct Roles in Antisaccade Generation.
AB  - The globus pallidus external segment (GPe) constitutes part of the indirect
      pathway of the basal ganglia. Because of inhibitory projections from the
      striatum, most GPe neurons are expected to reduce activity during movements.
      However, many GPe neurons in fact display increased activity. We previously found
      that both excitatory and inhibitory responses were modulated during antisaccades,
      when eyes were directed away from a visual stimulus. To elucidate the roles of
      these neurons during antisaccades, we examined neuronal activities as monkeys
      performed antisaccades, prosaccades, and NoGo tasks under 2 conditions. In the
      Deliberate condition, the task-rule was instructed by color of the fixation
      point, while in the Immediate condition, it was given by color of the target.
      Under both conditions, the increase-type neurons exhibited greater activity
      during antisaccades compared with the other tasks and neuronal activity
      negatively correlated with saccade latency. The decrease-type neurons also showed
      greater modulation during antisaccades but their activity was comparable between
      NoGo and antisaccade trials in the Immediate condition. These results suggest
      that the increase-type neurons might play a role in facilitating antisaccades,
      whereas the decrease-type neurons could mediate signals for reflexive saccade
      suppression. We propose that these GPe neurons are differently involved in basal
      ganglia pathways. 

PMID- 25577576
TI  - An fMRI Study of the Ventriloquism Effect.
AB  - In spatial perception, visual information has higher acuity than auditory
      information and we often misperceive sound-source locations when spatially
      disparate visual stimuli are presented simultaneously. Ventriloquists make good
      use of this auditory illusion. In this study, we investigated neural substrates
      of the ventriloquism effect to understand the neural mechanism of multimodal
      integration. This study was performed in 2 steps. First, we investigated how
      sound locations were represented in the auditory cortex. Secondly, we
      investigated how simultaneous presentation of spatially disparate visual stimuli
      affects neural processing of sound locations. Based on the population rate code
      hypothesis that assumes monotonic sensitivity to sound azimuth across populations
      of broadly tuned neurons, we expected a monotonic increase of blood oxygenation
      level-dependent (BOLD) signals for more contralateral sounds. Consistent with
      this hypothesis, we found that BOLD signals in the posterior superior temporal
      gyrus increased monotonically as a function of sound azimuth. We also observed
      attenuation of the monotonic azimuthal sensitivity by spatially disparate visual
      stimuli. The alteration of the neural pattern was considered to reflect the
      neural mechanism of the ventriloquism effect. Our findings indicate that
      conflicting audiovisual spatial information of an event is associated with an
      attenuation of neural processing of auditory spatial localization. 

PMID- 25577578
TI  - [Esophageal perforation caused by fish bone].

PMID- 25577579
TI  - [Xanthogranulomatous pyelonephritis with cutaneous fistula and a right flank
      mass].

PMID- 25577580
TI  - [Gastrointestinal stromal tumors associated with other primary neoplasms].

PMID- 25577581
TI  - [Large gastric folds: Differential diagnosis].

PMID- 25577582
TI  - [Transient cortical blindness after cerebral angiography].

PMID- 25577583
TI  - [Secondary hypertransaminasemia to macro-aspartate aminotransferase].

PMID- 25577584
TI  - [Determinants factors of Spanish researchers mobility in Health Sciences].

PMID- 25577585
TI  - [Neurological dysfunction and 15q11.2 microdeletion: Report of a new case].

PMID- 25577586
TI  - [Liver transplant in Spain: achievements and challenges].

PMID- 25577587
TI  - [Mean stay of patients with acute heart failure in short-stay units].

PMID- 25577588
TI  - [Hereditary hemochromatosis. Problems in diagnosis and treatment].

PMID- 25577589
TI  - [Acetylsalicylic acid desensitization in the new era of percutaneous coronary
      intervention].
AB  - Dual antiplatelet therapy is essential in patients undergoing percutaneous
      coronary intervention with stent implantation. Hypersensitivity to
      acetylsalicylic acid (ASA) limits treatment options. Desensitization to ASA has
      classically been studied in patients with respiratory tract disease. Over the
      last years, many protocols have been described about ASA desensitization in
      patients with ischemic heart disease, including acute coronary syndrome and the
      need for coronary stent implantation. It is important to know the efficacy and
      safety of ASA desensitization in these patients.

PMID- 25577590
TI  - Primary desmoplastic small round cell tumor of upper cervical lymph nodes.
AB  - Desmoplastic small round cell tumors (DSRCT) are rare malignancies that typically
      arise in the abdominopelvic cavities. They are very uncommon in the head and neck
      region. We present a case of an 11-year-old Caucasian male with a primary
      cervical lymph node tumor in the neck. Fine-needle aspiration cytology,
      histopathologic examination, immunohistochemical staining, and molecular genetic
      testing led to the diagnosis of DSRCT. Due to the very limited number of cases
      reported and the lack of staging criteria, the preferred management approach
      remains uncertain. 

PMID- 25577591
TI  - Treatment of lip hemangioma using forced dehydration with induced
      photocoagulation via diode laser: report of three cases.
AB  - Several vascular lesions are related to the lip area. There is no universally
      accepted protocol for the treatment of hemangiomas and vascular malformations. In
      the oral cavity, high-power lasers represent an excellent therapeutic option for
      this type of lesion. Their coagulative properties allow for the performance of
      procedures without the risk of bleeding, which promotes a better healing pattern
      and a differentiated postoperative appearance. This study describes three cases
      of lip hemangioma treated with forced dehydration with induced photocoagulation
      (FDIP) via diode laser. All the reported cases were followed up until complete
      healing of the operated area had total remission of lesions, with no
      complications or adverse effects. The findings of the present study suggest that
      FDIP is effective and useful in the treatment of hemangiomas in the oral cavity.
      Laser treatment of these lesions prevents their recurrence and is well tolerated
      by patients. 

PMID- 25577592
TI  - Anaphylaxis in America: A national physician survey.

PMID- 25577594
TI  - Cholangioscopic diagnosis of iatrogenic recurrent choledocholithiasis.

PMID- 25577593
TI  - Influence of childhood growth on asthma and lung function in adolescence.
AB  - BACKGROUND: Low birth weight and rapid infant growth in early infancy are
      associated with increased risk of childhood asthma, but little is known about the
      role of postinfancy growth in asthmatic children. OBJECTIVES: We sought to
      examine the associations of children's growth patterns with asthma, bronchial
      responsiveness, and lung function until adolescence. METHODS: Individual growth
      trajectories from birth until 10 years of age were estimated by using linear
      spline multilevel models for 9723 children participating in a population-based
      prospective cohort study. Current asthma at 8, 14, and 17 years of age was based
      on questionnaires. Lung function and bronchial responsiveness or reversibility
      were measured during clinic visits at 8 and 15 years of age. RESULTS: Rapid
      weight growth between 0 and 3 months of age was most consistently associated with
      increased risks of current asthma at the ages of 8 and 17 years, bronchial
      responsiveness at age 8 years, and bronchial reversibility at age 15 years. Rapid
      weight growth was associated with lung function values, with the strongest
      associations for weight gain between 3 and 7 years of age and higher forced vital
      capacity (FVC) and FEV1 values at age 15 years (0.12 [95% CI, 0.08 to 0.17] and
      0.11 [95% CI, 0.07 to 0.15], z score per SD, respectively) and weight growth
      between 0 and 3 months of age and lower FEV1/FVC ratios at age 8 and 15 years (
      0.13 [95% CI, -0.16 to -0.10] and -0.04 [95% CI, -0.07 to -0.01], z score per SD,
      respectively). Rapid length growth was associated with lower FVC and FVC1 values
      at age 15 years. CONCLUSION: Faster weight growth in early childhood is
      associated with asthma and bronchial hyperresponsiveness, and faster weight
      growth across childhood is associated with higher FVC and FEV1 values.

PMID- 25577595
TI  - EUS-guided pancreatic duct access and wire placement to facilitate dorsal duct
      cannulation after failed ERCP.

PMID- 25577596
TI  - Development and validation of an algorithm for classifying colonoscopy
      indication.
AB  - BACKGROUND: Accurate determination of colonoscopy indication is required for
      managing clinical programs and performing research; however, existing algorithms
      that use available electronic databases (eg, diagnostic and procedure codes) have
      yielded limited accuracy. OBJECTIVE: To develop and validate an algorithm for
      classifying colonoscopy indication that uses comprehensive electronic medical
      data sources. DESIGN: We developed an algorithm for classifying colonoscopy
      indication by using commonly available electronic diagnostic, pathology, cancer,
      and laboratory test databases and validated its performance characteristics in
      comparison with a comprehensive review of patient medical records. We also
      evaluated the influence of each data source on the algorithm's performance
      characteristics. SETTING: Kaiser Permanente Northern California healthcare
      system. PATIENTS: A total of 300 patients who underwent colonoscopy between 2007
      and 2010. INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Algorithm's
      sensitivity, specificity, and positive predictive value (PPV) for classifying
      screening, surveillance, and diagnostic colonoscopies. The reference standard was
      the indication assigned after comprehensive medical record review. RESULTS: For
      screening indications, the algorithm's sensitivity was 88.5% (95% confidence
      interval [CI], 80.4%-91.7%), specificity was 91.7% (95% CI, 87.0%-95.1%), and PPV
      was 83.3% (95% CI, 74.7%-90.0%). For surveillance indications, the algorithm's
      sensitivity was 93.4% (95% CI, 86.2%-97.5%), specificity was 92.8% (95% CI, 88.4%
      95.9%), and PPV was 85.0% (95% CI, 76.5%-91.4%). The algorithm's sensitivity,
      specificity, and PPV for diagnostic indications were 81.4% (95% CI, 73.0%-88.1%),
      96.8% (95% CI, 93.2%-98.8%), and 93.9% (95% CI, 87.2%-97.7%), respectively.
      LIMITATIONS: Validation was confined to a single healthcare system. CONCLUSION:
      An algorithm that uses commonly available modern electronic medical data sources
      yielded a high sensitivity, specificity, and PPV for classifying screening,
      surveillance, and diagnostic colonoscopy indications. This algorithm had greater
      accuracy than the indication listed on the colonoscopy report.

PMID- 25577597
TI  - Mycobacterium haemophilum bone and joint infection in HIV/AIDS: case report and
      literature review.
AB  - We report a case of disseminated Mycobacterium haemophilum osteomyelitis in a
      patient with advanced HIV infection, who later developed recurrent immune
      reconstitution inflammatory syndrome after commencement of antiretroviral
      therapy. We review previous reports of M. haemophilum bone and joint infection
      associated with HIV infection and describe the management of M. haemophilum
      associated immune reconstitution inflammatory syndrome, including the role of
      surgery as an adjunctive treatment modality and the potential drug interactions
      between antiretroviral and antimycobacterial agents. 

PMID- 25577598
TI  - Is resurfacing the patella cheaper? An economic analysis of evidence based
      medicine on patellar resurfacing.
AB  - BACKGROUND: Primary total knee arthroplasty is a high volume procedure which is
      expected to grow dramatically in the near future. The decision to resurface the
      patella has been discussed extensively in the literature yet the financial
      implications of resurfacing versus not resurfacing have not been demonstrated.
      METHODS: We identified all randomized controlled trials comparing patellar
      resurfacing to nonresurfacing in the past ten years and identified the total
      number of patellofemoral revision surgeries for both resurfaced and nonresurfaced
      patellas in each study. An expected-value decision tree analysis was created
      using only data from the randomized controlled trials. Actual costs collected
      from Medicare reimbursement rates were then applied to the model and a
      sensitivity analysis was performed. RESULTS: The expected value of primary total
      knee arthroplasty with patellar resurfacing was $13,788.48 while a primary total
      knee arthroplasty without patellar resurfacing was $14,016.41 after five years.
      The difference represents an additional $227.92 of Medicare dollars for every
      primary total knee arthroplasty performed without patellar resurfacing at five
      years. The model remains valid as long as patellofemoral revision rates after
      patellar resurfacing remain below 3.54% and patellofemoral revision rates after
      nonresurfaced patellas remain above 0.77%. CONCLUSIONS: While initially
      counterintuitive, resurfacing the patella during a primary total knee
      arthroplasty is the optimal financial strategy from a Medicare perspective over a
      mid term period.

PMID- 25577599
TI  - Management of thoracolumbar spine fractures with neurologic disorder.
AB  - Thoracic and lumbar fractures represent approximately 50% of neurologic spinal
      trauma. They lead to paraplegia or cauda equina syndrome depending on the level
      injured. In the acute phase, the extension of spinal cord lesions should be
      limited by immediately treating secondary systemic injury factors. Quick recovery
      of hemodynamic stability, with mean arterial blood pressure>85 mm Hg, appears
      essential. There is no clinical evidence in favor of high-dose corticosteroid
      protocols. Their effect on neurologic recovery is unproven, whereas they lead to
      a higher rate of secondary septic and pulmonary complications. Incomplete
      deficits (ASIA B-D) require urgent surgery. There is no consensus with regard to
      complete paraplegia (ASIA A), but early surgery can enable neurologic recovery in
      some cases. The principle of surgical treatment is based on spinal cord
      decompression, instrumentation and fracture reduction. Early stabilization of the
      spine improves respiratory function and shortens the duration of mechanical
      ventilation and thus intensive care unit stay. Depending on the severity of
      associated lesions, early surgery within 48 hours is beneficial in polytrauma
      patients. Percutaneous instrumentation combined with mini-open posterior
      decompression stabilizes the spine, limiting approach-related morbidity.

PMID- 25577600
TI  - The efficacy of fibrin sealant in knee surgery: A meta-analysis.
AB  - BACKGROUND: Fibrin sealant is frequently used in knee surgery as an adjuvant
      method for reducing postoperative bleeding, however, there is no consensus
      regarding the efficacy of fibrin sealant. HYPOTHESIS: Fibrin sealant achieves
      better efficacy in terms of blood loss control, transfusion rate and units in
      knee surgery compared with controls. METHODS: A search of the Cochrane
      Collaboration (2013 Issue 09), Embase (1974-2013.09), PubMed (1966-2013.09) and
      Chinese databases (up to 2013.09) were conducted. The Cochrane Collaboration's
      tool was used to assess for bias and data were analyzed by RevMan 5.29 software.
      RESULTS: This study included nine RCTs and four prospective comparative trials
      with a total of 1299 patients. Compared to the control, fibrin sealant achieved a
      decrease in hemoglobin reduction [MD=1.14, 95% CI (0.61-1.67)], transfusion rate
      [OR=0.36, 95% CI (0.25-0.51)], transfusion units [MD=0.47, 95% CI (0.24-0.71)],
      hospital stay [MD=2.22, 95% CI (0.56-3.88)] and the incidence of complications
      [OR=0.56, 95% CI (0.38-0.83)]. And it also reduced total blood loss, while there
      was no significant difference [MD=155.83, 95% CI (-525.02-213.15)]. CONCLUSION:
      Patients undergoing knee surgery would benefit from high-dose fibrin sealant with
      reduced transfusion rate and unit, hospital stay and complications, while they
      might benefit little from it in total blood loss. However, the effects of a low
      dose of fibrin in knee surgery remain inconclusive.

PMID- 25577601
TI  - Comments on: "posterior percutaneous reduction and fixation of thoraco-lumbar
      burst fractures" by L. Proietti, L. Scaramuzzo, G.R. Schiro et al. published in
      Orthop Traumatol Surg Res 2014;100:455-60.

PMID- 25577602
TI  - Conjoint regulation of glucagon concentrations via plasma insulin and glucose in
      dairy cows.
AB  - Insulin and glucagon are glucoregulatory hormones that contribute to glucose
      homeostasis. Plasma insulin is elevated during normoglycemia or hyperglycemia and
      acts as a suppressor of glucagon secretion. We have investigated if and how
      insulin and glucose contribute to the regulation of glucagon secretion through
      long term (48 h) elevated insulin concentrations during simultaneous hypoglycemia
      or euglycemia in mid-lactating dairy cows. Nineteen Holstein dairy cows were
      randomly assigned to 3 treatment groups: an intravenous insulin infusion (HypoG,
      n = 5) to decrease plasma glucose concentrations (2.5 mmol/L), a hyperinsulinemic
      euglycemic clamp to study effects of insulin at simultaneously normal glucose
      concentrations (EuG, n = 6) and a 0.9% saline infusion (NaCl, n = 8). Plasma
      glucose was measured at 5-min intervals, and insulin and glucose infusion rates
      were adjusted accordingly. Area under the curve of hourly glucose, insulin, and
      glucagon concentrations on day 2 of infusion was evaluated by analysis of
      variance with treatments as fixed effect. Insulin infusion caused an increase of
      plasma insulin area under the curve (AUC)/h in HypoG (41.9 +/- 8.1 mU/L) and EuG
      (57.8 +/- 7.8 mU/L) compared with NaCl (13.9 +/- 1.1 mU/L; P < 0.01). Induced
      hyperinsulinemia caused a decline of plasma glucose AUC/h to 2.3 +/- 0.1 mmol/L
      in HypoG (P < 0.01), whereas plasma glucose AUC/h remained unchanged in EuG (3.8
      +/- 0.2 mmol/L) and NaCl (4.1 +/- 0.1 mmol/L). Plasma glucagon AUC/h was lower in
      EuG (84.0 +/- 6.3 pg/mL; P < 0.05) and elevated in HypoG (129.0 +/- 7.0 pg/mL; P
      < 0.01) as compared with NaCl (106.1 +/- 5.4 pg/mL). The results show that
      intravenous insulin infusion induces elevated glucagon concentrations during
      hypoglycemia, although the same insulin infusion reduces glucagon concentrations
      at simultaneously normal glucose concentrations. Thus, insulin does not generally
      have an inhibitory effect on glucagon concentrations. If simultaneously glucose
      is low and insulin is high, glucagon is upregulated to increase glucose
      availability. Therefore, insulin and glucose are conjoint regulatory factors of
      glucagon concentrations in dairy cows, and the plasma glucose status is the key
      factor to decide if its concentrations are increased or decreased. This
      regulatory effect can be important for the maintenance of glucose homeostasis if
      insulin secretion is upregulated by other factors than high glucose such as high
      plasma lipid and protein concentrations at simultaneously low glucose.

PMID- 25577603
TI  - Ultrasonography as a prognostic and objective parameter in Achilles tendinopathy:
      a prospective observational study.
AB  - OBJECTIVES: To study prospectively whether structural changes determined by
      ultrasound scanning (US) can be used as prognostic markers for outcome in
      patients with symptomatic Achilles tendinopathy (AT) and to investigate whether
      there exists an association between US findings and pain measured by visual
      analog scale (VAS) and a general assessment score (GA). METHODS: 92 consecutive
      patients with AT symptoms were recruited from two outpatient clinics in
      rheumatology. The patients underwent a conservative treatment protocol consisting
      of reduced activities, controlled rehabilitation including eccentric exercises of
      the calf muscles and if needed supplemented with corticosteroid injections. The
      patients were examined clinically and by US (tendon thickness, hyper- and
      hypoechogenicity, calcification, bursitis, calcaneusspure, tenosynovitis, gray
      scale and color Doppler focusing on increased flow intra- or peritendinous). The
      clinical and US examination were performed at entry, 1, 2, 3 and at 6 month.
      RESULTS: 42 women and 50 men were included (mean age of 47 years). They had
      symptoms for more than 13 months and a symptomatic Achilles tendon mean thickness
      of 7.4+/-2.3mm. Heterogeneity at the initial examination was found to be a
      prognostic marker for the clinical outcome. Tendon thickness, hypoechogenicity
      and increased flow at any time point were significantly correlated to pain at
      function, palpatory pain and morning pain at the same time points. A reduction in
      tendon thickness was statistically associated with a decrease in palpatory pain.
      CONCLUSION: Heterogeneity is a prognostic marker in AT. Tendon thickness,
      hypoechogenicity and increased Doppler activity can be used as objective outcome
      parameters for the treatment effect of AT.

PMID- 25577605
TI  - Phycas: software for Bayesian phylogenetic analysis.
AB  - Phycas is open source, freely available Bayesian phylogenetics software written
      primarily in C++ but with a Python interface. Phycas specializes in Bayesian
      model selection for nucleotide sequence data, particularly the estimation of
      marginal likelihoods, central to computing Bayes Factors. Marginal likelihoods
      can be estimated using newer methods (Thermodynamic Integration and Generalized
      Steppingstone) that are more accurate than the widely used Harmonic Mean
      estimator. In addition, Phycas supports two posterior predictive approaches to
      model selection: Gelfand-Ghosh and Conditional Predictive Ordinates. The General
      Time Reversible family of substitution models, as well as a codon model, are
      available, and data can be partitioned with all parameters unlinked except tree
      topology and edge lengths. Phycas provides for analyses in which the prior on
      tree topologies allows polytomous trees as well as fully resolved trees, and
      provides for several choices for edge length priors, including a hierarchical
      model as well as the recently described compound Dirichlet prior, which helps
      avoid overly informative induced priors on tree length. 

PMID- 25577604
TI  - Serum lipid levels, body mass index, and their role in coronary artery
      calcification: a polygenic analysis.
AB  - BACKGROUND: Coronary artery calcification (CAC) is widely regarded as a
      cumulative lifetime measure of atherosclerosis, but it remains unclear what is
      the relationship between calcification and traditional risk factors for coronary
      artery disease (CAD) and myocardial infarction (MI). This study characterizes the
      genetic architecture of CAC by evaluating the overall impact of common alleles
      associated with CAD/MI and its traditional risk factors. METHODS AND RESULTS: On
      the basis of summary-association results from the CARDIoGRAMplusC4D study of
      CAD/MI, we calculated polygenic risk scores in 2599 participants of the Dutch and
      Belgian Lung Cancer Screening (NELSON) trial, in whom quantitative CAC levels
      (Agatston scores) were determined from chest computerized tomographic imaging
      data. The most significant polygenic model explained ~14% of the observed CAC
      variance (P=1.6*10(-11)), which points to a residual effect because of many as
      yet unknown loci that overlap between CAD/MI and CAC. In addition, we constructed
      risk scores based on published single-nucleotide polymorphism associations for
      traditional cardiovascular risk factors and tested these scores for association
      with CAC. We found nominally significant associations for genetic risk scores of
      low-density lipoprotein-cholesterol, total cholesterol, and body mass index,
      which were successfully replicated in 2182 individuals of the Heinz Nixdorf
      Recall Study. CONCLUSIONS: Pervasive polygenic sharing between CAC and CAD/MI
      suggests that a substantial fraction of the heritable risk for CAD/MI is mediated
      through arterial calcification. We also provide evidence that genetic variants
      associated with serum lipid levels and body mass index influence CAC levels.

PMID- 25577606
TI  - Marian diamond: the "mitochondrial eve" of successful aging.

PMID- 25577607
TI  - Filming "successful aging".

PMID- 25577608
TI  - Lower back pain.

PMID- 25577609
TI  - Evolution and Diversity of the Human Leukocyte Antigen(HLA).

PMID- 25577611
TI  - Effects of blood in veins of dragonfly wing on the vibration characteristics.
AB  - How the blood in veins of dragonfly wing affects its vibration characteristics is
      investigated. Based on the experimental results of the wing's morphology and
      microstructures, including the veins, the membranes and the pterostigma, accurate
      three-dimensional finite element models of the dragonfly forewing are developed.
      Considering the blood in veins, the total mass, mass distribution and the moments
      of inertia of the wing are studied. The natural frequencies/modal shapes are
      analyzed when the veins are filled with and without blood, respectively. The
      based natural frequency of the model with blood (189 Hz) is much closer to the
      experimental result. Relative to bending modal shapes, the torsional ones are
      affected more significantly by the blood. The results in this article reveal the
      multi-functions of the blood in dragonfly wings and have important implications
      for the bionic design of flapping-wing micro air vehicles.

PMID- 25577612
TI  - Clinical management of food allergy.
AB  - Food allergies are commonly seen by the practitioner, and managing these patients
      is often challenging. Recent epidemiologic studies report that as many as 1 in 13
      children in the United States may have a food allergy, which makes this an
      important disease process to appropriately diagnose and manage for primary care
      physicians and specialists alike. Having a understanding of the basic immunologic
      processes that underlie varying presentations of food-induced allergic diseases
      will guide the clinician in the initial workup. This review will cover the basic
      approach to understanding the immune response of an individual with food allergy
      after ingestion and will guide the clinician in applying appropriate testing
      modalities when needed by conducting food challenges if indicated and by
      educating the patient and his or her guardian to minimize the risk of accidental
      ingestion. 

PMID- 25577610
TI  - Cladograms with Path to Event (ClaPTE): a novel algorithm to detect associations
      between genotypes or phenotypes using phylogenies.
AB  - BACKGROUND: Associations between genotype and phenotype provide insight into the
      evolution of pathogenesis, drug resistance, and the spread of pathogens between
      hosts. However, common ancestry can lead to apparent associations between
      biologically unrelated features. The novel method Cladograms with Path to Event
      (ClaPTE) detects associations between character-pairs (either a pair of mutations
      or a mutation paired with a phenotype) while adjusting for common ancestry, using
      phylogenetic trees. METHODS: ClaPTE tests for character-pairs changing close
      together on the phylogenetic tree, consistent with an associated character-pair.
      ClaPTE is compared to three existing methods (independent contrasts, mixed model,
      and likelihood ratio) to detect character-pair associations adjusted for common
      ancestry. Comparisons utilize simulations on gene trees for: HIV Env, HIV
      promoter, and bacterial DnaJ and GuaB; and case studies for Oseltamavir
      resistance in Influenza, and for DnaJ and GuaB. Simulated data include both true
      positive/associated character-pairs, and true-negative/not-associated character
      pairs, used to assess type I (frequency of p-values in true-negatives) and type
      II (sensitivity to true-positives) error control. RESULTS AND CONCLUSIONS: ClaPTE
      has competitive sensitivity and better type I error control than existing
      methods. In the Influenza/Oseltamavir case study, ClaPTE reports no new
      permissive mutations but detects associations between adjacent (in primary
      sequence) amino acid positions which other methods miss. In the DnaJ and GuaB
      case study, ClaPTE reports more frequent associations between positions both from
      the same protein family than between positions from different families, in
      contrast to other methods. In both case studies, the results from ClaPTE are
      biologically plausible.

PMID- 25577613
TI  - Baked milk- and egg-containing diet in the management of milk and egg allergy.
AB  - Cow's milk (CM) and hen's egg allergies are among the most common food allergies
      in children. With evidence of increasing food allergy prevalence and more
      persistent disease, it has become vital to improve the management of CM and egg
      allergies. The ability to tolerate baked milk or egg, such as in a cake or
      muffin, has been associated with an increased chance of tolerance development.
      Studies report that about 70% of CM- and egg-allergic children can tolerate baked
      milk or egg and that incorporating baked milk or egg into the diet is well
      tolerated. Being able to add baked milk or egg into the diet can also increase
      quality of life by expanding the diet, boosting nutrition, and promoting
      inclusion in social activities. There is some debate over how baked milk and egg
      should be introduced, at home or in a supervised setting. Anaphylaxis and
      treatment with epinephrine during baked milk or egg challenges have been
      reported. Study of potential biomarkers to predict tolerability of baked milk and
      egg, such as serum specific IgE levels and skin prick test wheal diameters, is
      ongoing. Many parents can reliably report that their CM- or egg-allergic child is
      already consuming baked goods without symptoms. However, for those who cannot
      report such tolerance, the most prudent approach is to perform a supervised oral
      food challenge to determine the tolerability of baked milk and egg. The purpose
      of this article was to review the pathophysiology, clinical data, and safety of
      baked milk and egg and provide a practical guide to managing CM allergy and/or
      egg allergy. Recipes for baked milk and egg challenges and guidance on how to add
      baked milk and egg if tolerated to the child's regular diet are provided. 

PMID- 25577614
TI  - Food allergy and eosinophilic esophagitis: what do we do?
AB  - Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus
      triggered by foods and possibly environmental allergens. Common conditions that
      mimic EoE include gastroesophageal reflux disease and proton pump inhibitor
      responsive esophageal eosinophilia. These need to be excluded before confirming
      the diagnosis of EoE. Identification of food triggers for EoE using standard
      allergy tests remains challenging. Dietary therapy for EoE so far consists of
      test-directed elimination of foods, empiric elimination of common food allergens,
      or exclusive feeding of amino acid-based formulas, with variable success. No FDA
      approved medications yet exist for EoE. Topical corticosteroids to the esophagus
      are being used. EoE is a chronic disease; therefore, long-term therapy seems to
      be necessary to avoid potential long-term complications such as esophageal
      remodeling and strictures. Optimal long-term therapies and follow-ups are still
      not established; therefore, discussion with patients and families regarding the
      choice of therapy is important to ensure the best possible outcomes from a
      medical and social standpoint. In this article, we discuss all the above issues
      in detail by using a hypothetical case; highlighting in a stepwise manner what is
      known with respect to diagnosis, work-up, and management of EoE; and discussing
      gaps in knowledge that need to be addressed in the future. 

PMID- 25577615
TI  - Allergist-reported trends in the practice of food allergen oral immunotherapy.
AB  - Food allergen oral immunotherapy (OIT) is an experimental, immune-modifying
      therapy that may induce clinical desensitization in some patients. OIT is still
      in early phase clinical research, but some providers may offer OIT as a clinical
      service. To understand the current practices of allergists who perform OIT, an
      online survey was sent by e-mail to members of the American Academy of Allergy
      Asthma & Immunology. Among 442 respondents, 61 reported participating in using
      OIT (13.8%), including 28 in nonacademic settings. Informed consent for OIT was
      obtained by 91.3%, institutional review board approval by 47.7% and
      Investigational New Drug approval by 38.1%. Compared with nonacademic
      participants, more academic participants used peanut OIT, obtained institutional
      review board and Investigational New Drug (P < .0001 respectively), and
      challenged patients before entry (P = .008). More nonacademic providers billed
      the patient or insurance for reimbursement (P < .0001). Low reported regard for
      the importance for US Food and Drug Administration approval or a standardized
      product (increased odds), and a high regard for better safety data (decreased
      odds) were associated with considering offering OIT as a service. Significant
      differences exist with OITs that occur in academic versus nonacademic settings.
      Further assessment is needed regarding the different motivations and practice
      styles among providers who offer OIT and those who are considering doing so.

PMID- 25577616
TI  - The changing field of food allergy.

PMID- 25577617
TI  - Prevalence and predictors of food allergy in Canada: a focus on vulnerable
      populations.
AB  - BACKGROUND: Studies suggest that individuals of low education and/or income, new
      Canadians (immigrated <10 years ago), and individuals of Aboriginal identity may
      have fewer food allergies than the general population. However, given the
      difficulty in recruiting such populations (hereafter referred to as vulnerable
      populations), by using conventional survey methodologies, the prevalence of food
      allergy among these populations in Canada has not been estimated. OBJECTIVES: To
      estimate the prevalence of food allergy among vulnerable populations in Canada,
      to compare with the nonvulnerable populations and to identify demographic
      characteristics predictive of food allergy. METHODS: By using 2006 Canadian
      Census data, postal codes with high proportions of vulnerable populations were
      identified and households were randomly selected to participate in a telephone
      survey. Information on food allergies and demographics was collected. Prevalence
      estimates were weighted by using Census data to account for the targeted
      sampling. Multivariable logistic regression was used to identify predictors of
      food allergy. RESULTS: Of 12,762 eligible households contacted, 5734 households
      completed the questionnaire (45% response rate). Food allergy was less common
      among adults without postsecondary education versus those with postsecondary
      education (6.4% [95% CI, 5.5%-7.3%] vs 8.9% [95% CI, 7.7%-10%]) and new Canadians
      versus those born in Canada (3.2% [95% CI, 2.2%-4.3%] vs 8.2% [95% CI, 7.4%
      9.1%]). There was no difference in prevalence between those of low and of high
      income or those with and without Aboriginal identity. CONCLUSION: Analysis of our
      data suggests that individuals of low education and new Canadians self-report
      fewer allergies, which may be due to genetics, environment, lack of appropriate
      health care, or lack of awareness of allergies, which reduces self-report.

PMID- 25577618
TI  - Oral food challenge and food allergy quality of life in caregivers of children
      with food allergy.
AB  - BACKGROUND: Food allergy is associated with diminished patient and caregiver
      quality of life (QoL). Although oral food challenge (OFC) improves QoL of
      individuals with food allergy, its effects on caregiver QoL are unknown.
      OBJECTIVES: To determine if differences in caregiver QoL exist based on their
      child undergoing OFC. METHODS: Caregivers of individuals with food allergy who
      underwent OFCs between 2001 and 2012 at the University of Michigan Food Allergy
      Center completed the Food Allergy Quality of Life-Parental Burden index and a
      questionnaire that assessed details of the most-severe reaction by an individual
      with food allergy. Results were compared with 305 caregivers of individuals with
      food allergy who were unchallenged. All questionnaire data regarding the
      characteristics of the reactions of individuals with food allergy were verified
      through chart review. RESULTS: A total of 115 caregivers of individuals with food
      allergy who were undergoing OFC completed the QoL assessment. Caregivers of
      individuals with food allergy who were undergoing OFC had a significantly lower
      (better) QoL score than controls who were not challenged (1.5 vs 1.88; P = .02).
      Furthermore, within the challenged cohort, there was no significant difference in
      QoL score between those with a passing OFC (eg, non-reactive) and a failing OFC
      (eg, reactive) (1.42 vs 1.34; P = .83). In an adjusted linear regression model,
      the QoL score was significantly better among caregivers of individuals with food
      allergy who were undergoing OFC and with an income >$50,000 but significantly
      worsened for caregivers with multiple individuals with food allergy or if the
      individual with food allergy had atopic dermatitis. CONCLUSION: The caregiver QoL
      score is better with individuals with food allergy who underwent OFC versus
      controls who were unchallenged but not significantly different based on OFC
      outcome. QoL is, in addition, moderated by income, the presence of atopic
      dermatitis, and having multiple individuals with food allergy. OFC is associated
      with better caregiver QoL, irrespective of challenge outcome.

PMID- 25577619
TI  - Early treatment of food-induced anaphylaxis with epinephrine is associated with a
      lower risk of hospitalization.
AB  - BACKGROUND: Food-induced anaphylaxis (FIA) is potentially life threatening.
      Prompt administration of epinephrine is universally recommended by current
      treatment guidelines. OBJECTIVE: To identify factors associated with early
      epinephrine treatment for FIA and to specifically examine the association between
      early epinephrine treatment and hospitalization. METHODS: A chart review study
      conducted at Hasbro Children's Hospital/Rhode Island Hospital. By using the
      International Classification of Diseases, Ninth Revision codes, we identified all
      patients who presented to the emergency department with FIA between January 1,
      2004, and December 31, 2009. Early epinephrine treatment was defined as receipt
      of epinephrine before arrival to the emergency department. The independent
      association between early epinephrine treatment and hospitalization was assessed
      using logistic regression. RESULTS: Among the 384 emergency department visits for
      FIA identified during the study period, 234 patients received epinephrine (61%).
      Among this subset, most (164 [70%]) received early epinephrine treatment, whereas
      a smaller number of patients (70 [30%]) first received epinephrine in the
      emergency department (late treatment). Patients who received early epinephrine
      treatment were older (7.4 vs 4.3 years; P = .008), were more likely to have a
      known food allergy (66% vs 34%; P < .001), and were more likely to own an
      epinephrine autoinjector (80% vs 23%; P < .001). Patients treated early were less
      likely to be hospitalized (17% vs 43%; P < .001). After adjusting for age, sex,
      and race, the patients who received early epinephrine treatment remained at
      significantly decreased risk of hospitalization compared with those who received
      late epinephrine treatment (odds ratio 0.25 [95% CI, 0.12-0.49]). CONCLUSIONS: In
      this population, early treatment of FIA with epinephrine was associated with
      significantly lower risk of hospitalization. Accordingly, this study supports the
      benefit of prompt administration of epinephrine for the treatment of FIA.

PMID- 25577620
TI  - Nannies' knowledge, attitude, and management of food allergies of children: an
      online survey.
AB  - BACKGROUND: Rates of food allergies in children as well as the rate of families
      who employ nannies have increased dramatically over the past decade. It is
      essential that nannies have the knowledge and tools necessary to recognize and
      treat food allergy reactions. OBJECTIVE: To identify gaps in knowledge in the
      nanny population with regard to food allergy in children. METHODS: A Web-based
      survey was sent by e-mail to 709 nannies. RESULTS: A total of 153 nannies (22%)
      completed the online survey: 26% of respondents had formal educational training
      at a nanny school; 99% recognized food allergy as a potentially fatal event; 37%
      reported caring for a child with food allergies. Of these, 71% had food allergy
      action plans, and 63% had epinephrine available. A total of 71% reported training
      on administering epinephrine. The nannies' major concerns included accidental
      ingestion and discomfort in administering epinephrine. A total of 36% were
      uncomfortable with recognizing a food allergy emergency, whereas 46% were
      uncomfortable administering epinephrine; 6% thought that a sensitized child could
      safely eat a small amount of allergenic food, whereas 14% believed that dilution
      with water might reduce an allergic reaction. A total of 66% desired additional
      information about recognizing food allergies, and 71% agreed that food allergy
      training should be required for all nannies. CONCLUSION: Nannies demonstrated
      gaps in knowledge with regard to food allergy in children, which reflects the
      need for more stringent training and education. Increased communication among
      parents, nannies, and physicians is needed to protect children with food allergy.

PMID- 25577621
TI  - Household costs associated with objectively diagnosed allergy to staple foods in
      children and adolescents.
AB  - BACKGROUND: We previously reported that indirect and intangible costs burden
      households with a food allergic adult. We now extend our investigation to
      households with food allergic children and adolescents. OBJECTIVE: The objective
      of this study was to estimate direct, indirect, and intangible costs of food
      allergy in households with a child and/or adolescent with objectively diagnosed
      allergy to staple foods (cow's milk, hen's egg, and/or wheat), and to compare
      these costs with age- and sex-matched controls. METHODS: Direct and indirect cost
      parent-reported data collected via the Food Allergy Socio-Economic Questionnaire
      of 84 children (0-12 years) and 60 adolescents (13-17 years) with objectively
      diagnosed allergy to staple foods ("cases") and age- and sex-matched controls (n
      = 94 children; n = 56 adolescents) were compared. Annual household costs were
      calculated. Total household costs included direct plus indirect costs. Intangible
      costs included parent-reported health of their child and/or adolescent, standard
      of living, and perceptions of well-being. RESULTS: Amongst cases, total household
      costs were higher by ?3961 for children and ?4792 for adolescents versus controls
      (P < .05), and were driven by direct (eg, medications) and indirect (eg, time
      with health care professionals) costs. For children only, a history of
      anaphylaxis was associated with higher direct costs than no anaphylaxis (?13,016
      vs ?10,044, P < .05). Intangible costs (eg, parent-reported health of a child
      and/or adolescent) were significantly impacted amongst cases versus controls (P <
      .01). CONCLUSION: Households with a child and/or adolescent with objectively
      diagnosed allergy to staple foods have higher total household costs than
      controls. Direct and indirect costs were significantly higher for cases versus
      controls amongst children only. Amongst both age groups, such allergy adversely
      impacted intangible costs.

PMID- 25577622
TI  - Epinephrine in anaphylaxis: higher risk of cardiovascular complications and
      overdose after administration of intravenous bolus epinephrine compared with
      intramuscular epinephrine.
AB  - BACKGROUND: Epinephrine is the drug of choice for the management of anaphylaxis,
      and fatal anaphylaxis is associated with delayed epinephrine administration. Data
      on adverse cardiovascular (CV) complications and epinephrine overdose are
      limited. OBJECTIVE: To compare rates of CV adverse events and epinephrine
      overdoses associated with anaphylaxis management between various routes of
      epinephrine administration among patients with anaphylaxis in the emergency
      department. METHODS: This was an observational cohort study from April 2008 to
      July 2012. Patients in the emergency department who met diagnostic criteria for
      anaphylaxis were included. We collected demographics; route of epinephrine
      administration; trigger; overdose; and adverse CV events, including arrhythmia,
      cardiac ischemia, stroke, angina, and hypertension. RESULTS: The study cohort
      included 573 patients, of whom, 301 (57.6%) received at least 1 dose of
      epinephrine. A total of 362 doses of epinephrine were administered to 301
      patients: 67.7% intramuscular (IM) autoinjector, 19.6% IM injection, 8.3%
      subcutaneous injection, 3.3% intravenous (IV) bolus, and 1.1% IV continuous
      infusion. There were 8 CV adverse events and 4 overdoses with 8 different
      patients. All the overdoses occurred when epinephrine was administered IV bolus.
      Adverse CV events were associated with 3 of 30 doses of IV bolus epinephrine
      compared with 4 of 316 doses of IM epinephrine (10% vs 1.3%; odds ratio 8.7 [95%
      CI, 1.8-40.7], P = .006). Similarly, overdose occurred with 4 of 30 doses of IV
      bolus epinephrine compared with 0 of 316 doses of IM epinephrine (13.3% vs 0%;
      odds ratio 61.3 [95% CI, 7.5 to infinity], P < .001). CONCLUSION: The risk of
      overdose and adverse CV events is significantly higher with IV bolus epinephrine
      administration. Analysis of the data supports the safety of IM epinephrine and a
      need for extreme caution and further education about IV bolus epinephrine in
      anaphylaxis.

PMID- 25577623
TI  - Age-based differences in the diagnosis and management of esophageal eosinophilia.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is hallmarked by esophageal
      eosinophilia, >15 eosinophils(eos)/high-powered field (hpf), unresponsive to acid
      inhibition, and varied symptomatology. EoE consensus guidelines do not
      discriminate based on age for initiating treatment. OBJECTIVE: To evaluate if age
      related differences exist in managing esophageal eosinophilia and EoE within a
      university population. METHODS: In a retrospective cohort study from a referral
      center, the medical records of 426 pediatric and adult patients with at least 1
      presenting symptom of esophagitis, reflux, or upper gastrointestinal dysfunction,
      who underwent esophageal biopsy between 2009 and 2011 were analyzed for age-based
      differences in care in diagnosing and managing esophageal eosinophilia. RESULTS:
      For these patients, 79.6% (336/426) had >=15 eos/hpf in biopsy specimens, which
      was not associated with age. Significantly fewer adults than children with >=15
      eos/hpf were diagnosed with EoE (P < .001), referred for allergy evaluation (P <
      .001), started on swallowed steroid therapy (P < .001), or underwent repeated
      biopsy (P < .001). Increasing age, atopy, and increasing biopsy peak eos count
      moderated these effects, but the adjusted predicted probabilities for these
      outcomes were significantly lower among adults. Restriction for an 8-week
      prebiopsy proton-pump inhibitor trial did not alter the age-based relationships
      for an allergy referral or repeated biopsy. CONCLUSIONS: Numerous age-based
      differences in the management of symptomatic patients with esophageal
      eosinophilia existed in this cohort. Adults were significantly less likely than
      children to receive a clinical diagnosis of EoE, allergy referral, or steroid
      treatment, or to have a repeated biopsy. Even when stratified for an 8-week
      prebiopsy proton-pump inhibitor trial, advancing age was associated with lower
      odds of referral or repeated biopsy. Further study is necessary to better
      understand why discrepancies exist and their potential ramifications.

PMID- 25577624
TI  - Outcomes of allergy/immunology follow-up after an emergency department evaluation
      for anaphylaxis.
AB  - BACKGROUND: Anaphylaxis guidelines currently recommend referring patients with
      anaphylaxis seen in the emergency department (ED) to an allergist for follow up.
      OBJECTIVE: The objective of our study was to evaluate outcomes of
      allergy/immunology follow-up after an ED visit for anaphylaxis. METHODS: A
      retrospective health records review was conducted from April 2008 to August 2012.
      Charts were reviewed independently by 2 allergists to determine outcomes.
      Descriptive statistics with corresponding 95% CIs were calculated. RESULTS: Among
      573 patients seen in the ED who met anaphylaxis diagnostic criteria, 217 (38%)
      had a documented allergy/immunology follow-up. After allergy/immunology
      evaluation, 16 patients (7% [95% CI, 5%-12%]) had anaphylaxis ruled out. Among
      those with an unknown ED trigger (n = 74), 24 (32% [95% CI, 23%-44%]) had a
      trigger identified; and, among those who had a specific suspected ED trigger (n =
      143), 9 (6% [95% CI, 3%-12%]) had a trigger identified in a category other than
      the one suspected in the ED, and 28 (20% [95% CI, 14%-27%]) had an unknown
      trigger. Thus, there were a total of 77 patients (35% [95% CI, 29%-42%]) who had
      an alteration in the diagnosis of anaphylaxis or trigger after allergy/immunology
      evaluation. Four patients (2% [95% CI, 0.7%-4.6%]) were diagnosed with a mast
      cell activation disorder, and 13 patients (6% [95% CI, 4%-10%]) underwent
      immunotherapy or desensitization. CONCLUSION: Overall, 35% of the patients with
      suspected anaphylaxis in the ED had an alteration in the diagnosis or suspected
      trigger after allergy/immunology evaluation. These results underscore the
      importance of allergy/immunology follow-up after an ED visit for anaphylaxis.

PMID- 25577625
TI  - Comprehensive allergy evaluation is useful in the subsequent care of patients
      with drug hypersensitivity reactions during anesthesia.
AB  - BACKGROUND: For patients with a history of drug hypersensitivity reaction (HSR)
      during anesthesia, strategies to minimize risk with subsequent anesthesia are
      unclear. Identification of the cause of HSR during anesthesia remains
      challenging. OBJECTIVE: To determine the success of a comprehensive allergy
      evaluation and management plan for patients with HSR during anesthesia, including
      identification of the causative agent and review of outcomes during subsequent
      anesthesia exposure. METHODS: We performed chart reviews of patients referred for
      the evaluation of HSR during anesthesia between 2003 and 2012. Data collection
      included patient characteristics, signs/symptoms of HSR during anesthesia, and
      subsequent outcomes. Patients underwent comprehensive allergy evaluation
      including skin testing for identifying potential culprit agents, and the results
      were used to provide recommendations for any subsequent anesthesia. RESULTS: Over
      the 10-year study period, 73 patients with HSR during anesthesia were referred
      for further evaluation. Thirteen patients (18%) had positive skin test results to
      a drug received during anesthesia. One patient with a positive skin test result
      was diagnosed with mastocytosis. The causative agents identified in these 13
      patients included latex, beta-lactam antibiotics, neuromuscular blockers,
      tetracaine, odansetron, and fentanyl. On follow-up, 47 of the 73 patients (64%)
      subsequently underwent procedures requiring anesthesia. Using our recommendations
      from evaluation and testing, 45 of these 47 patients (96%) successfully tolerated
      subsequent anesthesia. The 2 patients who developed recurrent HSR during
      anesthesia were later diagnosed with mast cell disorders. CONCLUSIONS: Our
      comprehensive evaluation and management plan minimizes risk with subsequent
      anesthesia even when the cause of HSR could not be identified. Baseline tryptase
      levels may be helpful in this patient population to diagnose mast cell disorders.

PMID- 25577626
TI  - Antibiotics are an important identifiable cause of perioperative anaphylaxis in
      the United States.
AB  - BACKGROUND: The diagnosis of perioperative anaphylaxis (PA) remains challenging,
      given its clinical setting, exposure to multiple medications, and rarity.
      Previous reports have found that PA is most frequently caused by neuromuscular
      blocking agents. OBJECTIVE: To determine characteristics and causes of PA at our
      center. METHODS: We performed a retrospective medical record review to identify
      patients with anaphylaxis. Cases were further categorized by manifestations of
      anaphylaxis, age, sex, atopy, timing, tryptase level, and previous PA events.
      Cases with a cause identified by skin or in vitro tests were classified as IgE
      mediated anaphylaxis. RESULTS: Thirty cases were identified. Seventeen (57%) had
      an identifiable cause: antibiotics in 10 (59%)-beta-lactams in and metronidazole
      in 1; latex in 3 (18%); and neuromuscular blockers in 4 (23%). There was no
      identifiable cause in 13 cases. The most frequent presenting sign of PA was
      hypotension (97%). Seven patients (23%) presented with cardiac arrest. A minority
      (17%) exhibited urticaria. Only four had a history of atopy. Most of the
      reactions occurred during the anesthesia induction phase. Elevated serum tryptase
      level was found in 10 of 10 (100%) cases of IgE-mediated anaphylaxis compared
      with 4 of 10 (40%) cases without an identifiable cause. CONCLUSIONS: We found
      that antibiotics were the most common identifiable cause of PA. Our findings
      imply that antibiotic exposure warrants careful attention in the evaluation and
      management of patients with PA, particularly for those who require repeat and/or
      future surgeries.

PMID- 25577627
TI  - Intraoperative and procedure-related anaphylaxis.

PMID- 25577628
TI  - A nonallergic mechanism for nut-induced wheeze.

PMID- 25577629
TI  - Life-threatening intraoperative anaphylaxis to gelatin in Floseal during
      pediatric spinal surgery.

PMID- 25577630
TI  - Patent blue anaphylaxis: case report.

PMID- 25577631
TI  - Prevalence and characteristics of adult-onset food allergy.

PMID- 25577632
TI  - Profile of a milk-allergic patient who tolerated partially hydrolyzed whey
      formula.

PMID- 25577633
TI  - Fixed food eruption caused by peanut and cashew: A case report and review of the
      literature.

PMID- 25577634
TI  - The development of IgE-mediated immediate hypersensitivity after the diagnosis of
      eosinophilic esophagitis to the same food.

PMID- 25577635
TI  - Adherence to extensively heated egg and cow's milk after successful oral food
      challenge.

PMID- 25577636
TI  - Long-term increase in epinephrine availability associated with school nurse
      training in food allergy.

PMID- 25577637
TI  - The predictive relationship between peanut- and Ara h 2-specific serum IgE
      concentrations and peanut allergy.

PMID- 25577638
TI  - Food allergies affect growth in children.

PMID- 25577639
TI  - A case of food protein-induced enterocolitis syndrome to mushrooms challenging
      currently used diagnostic criteria.

PMID- 25577640
TI  - Safe vaccination of patients with egg allergy by using live attenuated influenza
      vaccine.

PMID- 25577641
TI  - Influenza vaccine and egg allergy: nearing the end of an evidence-based journey.

PMID- 25577642
TI  - Perioperative anaphylaxis.

PMID- 25577643
TI  - An infant with atopic dermatitis and itching after ingestion of milk.

PMID- 25577644
TI  - Peptidoglycan recognition protein-triggered induction of Escherichia coli gene in
      Drosophila melanogaster.
AB  - Interaction between the host and pathogen determines the fate of both organisms
      during the infectious state. The host is equipped with a battery of immune
      reactions, while the pathogen displays a variety of mechanisms to compromise host
      immunity. Although bacteria alter their pattern of gene expression in host
      organisms, studies to elucidate the mechanism behind this are only in their
      infancy. We here examined the possibility that host immune proteins directly
      participate in the change of gene expression in bacteria. Escherichia coli was
      treated with a mixture of the extracellular region of peptidoglycan recognition
      protein (PGRP)-LC and the antimicrobial peptide attacin of Drosophila, and
      subjected to DNA microarray analysis for mRNA repertoire. We identified 133
      annotated genes whose mRNA increased after the treatment, and at least four of
      them were induced in response to PGRP-LC. One such gene, lipoprotein-encoding
      nlpI, showed a transient increase of mRNA in adult flies depending on PGRP-LC but
      not PGRP-LE. NlpI-lacking E. coli had a lowered growth rate and/or viability in
      flies than the parental strain. These results suggest that a host immune receptor
      triggers a change of gene expression in bacteria simultaneously with their
      recognition and induction of immune responses. 

PMID- 25577645
TI  - Substrate-dependent nitric oxide synthesis by secreted endoplasmic reticulum
      aminopeptidase 1 in macrophages.
AB  - In this study, we examined the role of aminopeptidases with reference to
      endoplasmic reticulum aminopeptidase 1 (ERAP1) in nitric oxide (NO) synthesis
      employing murine macrophage cell line RAW264.7 cells activated by
      lipopolysaccharide (LPS) and interferon (IFN)-gamma and LPS-activated peritoneal
      macrophages derived from ERAP1 knockout mouse. When NO synthesis was measured in
      the presence of peptides having N-terminal Arg, comparative NO synthesis was seen
      with that measured in the presence of Arg. In the presence of an aminopeptidase
      inhibitor amastatin, NO synthesis in activated RAW264.7 cells was significantly
      decreased. These results suggest that aminopeptidases are involved in the NO
      synthesis in activated RAW264.7 cells. Subsequently, significant reduction of NO
      synthesis was observed in ERAP1 knockdown cells compared with wild-type cells.
      This reduction was rescued by exogenously added ERAP1. Furthermore, when
      peritoneal macrophages prepared from ERAP1 knockout mouse were employed,
      reduction of NO synthesis in knockout mouse macrophages was also attributable to
      ERAP1. In the presence of amastatin, further reduction was observed in knockout
      mouse-derived macrophages. Taken together, these results suggest that several
      aminopeptidases play important roles in the maximum synthesis of NO in activated
      macrophages in a substrate peptide-dependent manner and ERAP1 is one of the
      aminopeptidases involved in the NO synthesis. 

PMID- 25577647
TI  - Multiresidue determination of fluoroquinolones in poultry muscle and kidney
      according to the regulation 2002/657/EC. A systematic comparison of two different
      approaches: Liquid chromatography coupled to high-resolution mass spectrometry or
      tandem mass spectrometry.
AB  - This work involved the optimization and validation of two methods according to
      the Commission Decision 2002/657/EC directives for determining fluoroquinolones
      residues in samples of poultry muscle and kidney: ciprofloxacin, danofloxacin,
      difloxacin, enrofloxacin, flumequine, marbofloxacin, nalidixic acid, norfloxacin,
      ofloxacin, oxolinic acid, pipemidic acid and sarafloxacin. The extraction
      procedure was based on a QuEChERS approach, whose optimization employed a Box
      Behnken 3(3) factorial design. A liquid chromatography-tandem mass spectrometry
      method (LC-MS/MS) was developed for determining the twelve analytes using the
      multiple reaction monitoring mode (MRM). Accuracy, evaluated by recovery studies,
      varied from 88.8 to 112.2% for the selected levels with RSD values lower than
      12.3%. The second validated method employed high resolution mass spectrometry
      (HRMS) performed in the single ion monitoring mode (SIM), determining nine among
      twelve analytes. The validation parameters were evaluated as satisfactory, with
      recoveries from 82.5 to 114.4% and RSD lower than 8.7%. Decision limits and
      detection capabilities for both methods were reported. The two methods were
      statistically compared using the Student's t test, at 95% confidence level,
      resulting in no significant difference. 

PMID- 25577646
TI  - Filamin C, a dysregulated protein in cancer revealed by label-free quantitative
      proteomic analyses of human gastric cancer cells.
AB  - Gastric cancer (GC) is the fourth and fifth most common cancer in men and women,
      respectively. We identified 2,750 proteins at false discovery rates of 1.3%
      (protein) and 0.03% (spectrum) by comparing the proteomic profiles of three GC
      and a normal gastric cell lines. Nine proteins were significantly dysregulated in
      all three GC cell lines, including filamin C, a muscle-specific filamin and a
      large actin-cross-linking protein. Downregulation of filamin C in GC cell lines
      and tissues were verified using quantitative PCR and immunohistochemistry. Data
      mining using public microarray datasets shown that filamin C was significantly
      reduced in many human primary and metastasis cancers. Transient expression or
      silencing of filamin C affected the proliferation and colony formation of cancer
      cells. Silencing of endogenous filamin C enhanced cancer cell migration and
      invasion, whereas ectopic expression of filamin C had opposing effects. Silencing
      of filamin C increased the expression of matrix metallopeptidase 2 and improved
      the metastasis of prostate cancer in a zebrafish model. High filamin C associated
      with better prognosis of prostate cancer, leukemia and breast cancer patients.
      These findings establish a functional role of filamin C in human cancers and
      these data will be valuable for further study of its mechanisms. 

PMID- 25577648
TI  - The development of a hydrodynamic flow assisted double junction interface for
      signal improvement in capillary electrophoresis-mass spectrometry using
      positively charged nonvolatile additives.
AB  - To alleviate signal suppression resulting from nonvolatile positive ion
      additives, a hydrodynamic flow assisted double junction capillary electrophoresis
      mass spectrometry (CE-MS) interface was proposed. The double junction interface
      which could alleviate the ion suppression due to nonvolatile negative ion
      additives was modified so that a hydrodynamic flow could be introduced to the
      interface. Using this setup, the apparent velocity of the ions was determined
      based on its electrophoretic mobility, electroosmotic flow in the transfer
      capillary, and hydrodynamic flow introduced by the syringe pump. CE-MS analysis
      of positively charged triazines was performed to demonstrate the practical value
      of this approach by using cetyltrimethylammonium ion (CTA(+)) as an additive.
      Because the separation column was dynamically coated with CTA(+), the EOF was
      reversed and the separation was performed under counter EOF mode. Under an
      appropriate hydrodynamic flow, the analytes (triazines) could be propagated
      toward the MS, whereas the additive (CTA(+)) ion was retained in the interface.
      Consequently, the problem of signal suppression by CTA(+) was alleviated, and the
      signals were enhanced more than 20-fold. 

PMID- 25577649
TI  - Use of ion-pairing reagent for improving iodine speciation analysis in seaweed by
      pressure-driven capillary electrophoresis and ultraviolet detection.
AB  - This study achieved resolution improvement for iodine speciation in the presence
      of an ion-pairing reagent by a pressure-driven capillary electrophoresis (CE)
      system. Addition of 0.01mM tetrabutyl ammonium hydroxide (TBAH) as the ion
      pairing reagent into the electrophoretic buffer resulted in the complete
      separation of four iodine species (I(-), IO3(-), mono-iodothyrosine-MIT and di
      iodothyrosine-DIT), because of the electrostatic interaction between TBAH and the
      negatively charged analytes. A +16kV separation voltage was applied along the
      separation capillary (50MUm i.d., 80cm total and 60cm effective) with the inlet
      grounded. The detection wavelength was fixed at 210nm, and the pressure-driven
      flow rate was set at 0.12mLmin(-1) with an injected volume of 2MUL. The optimal
      electrolyte consisted of 2mM borate, 2mM TBAH and 80% methanol with pH adjusted
      to 8.5. Baseline separation of iodine species was achieved within 7min. The
      detection limits for I(-), IO3(-), MIT and DIT were 0.052, 0.040, 0.032 and
      0.025mgL(-1), respectively. The relative standard deviations of peak heights and
      areas were all below 3% for 5mgL(-1) and 5% for 1mgL(-1). Application of the
      proposed method was demonstrated by speciation analysis of iodine in two seaweed
      samples. The developed method offered satisfactory recoveries in the 91-99% range
      and good precisions (<5%). Good agreement between the determined values by the
      proposed CE method and the HPLC-ICP-MS method was also obtained. All results
      proved its great potential in routine analysis of iodine speciation in
      environmental, food and biological samples. 

PMID- 25577650
TI  - Mining web-based data to assess public response to environmental events.
AB  - We explore how the analysis of web-based data, such as Twitter and Google Trends,
      can be used to assess the social relevance of an environmental accident. The
      concept and methods are applied in the shutdown of drinking water supply at the
      city of Toledo, Ohio, USA. Toledo's notice, which persisted from August 1 to 4,
      2014, is a high-profile event that directly influenced approximately half a
      million people and received wide recognition. The notice was given when excessive
      levels of microcystin, a byproduct of cyanobacteria blooms, were discovered at
      the drinking water treatment plant on Lake Erie. Twitter mining results
      illustrated an instant response to the Toledo incident, the associated collective
      knowledge, and public perception. The results from Google Trends, on the other
      hand, revealed how the Toledo event raised public attention on the associated
      environmental issue, harmful algal blooms, in a long-term context. Thus, when
      jointly applied, Twitter and Google Trend analysis results offer complementary
      perspectives. Web content aggregated through mining approaches provides a social
      standpoint, such as public perception and interest, and offers context for
      establishing and evaluating environmental management policies. 

PMID- 25577652
TI  - The posterior ligamentous complex inflammatory syndrome: spread of fluid and
      inflammation in the retrodural space of Okada.
AB  - The retrodural space of Okada is situated dorsal to the ligamentum flavum in the
      interlaminar space, and provides communication between contralateral facet
      joints. MRI will often demonstrate heterogeneous signal abnormality with contrast
      enhancement in this space and several communicating compartments of the posterior
      ligamentous complex: bilateral facet joints, adventitial interspinous bursae, or
      retrodural cysts penetrating the ligamentum flavum. Pars interarticularis defects
      are frequently present. This imaging pattern may be associated with axial low
      back pain and/or radicular pain. Recognition of this pattern at MRI has distinct
      implications for image interpretation, unifying prior reports of involvement of
      individual components of the posterior ligamentous complex. Its recognition will
      also affect planning for therapeutic interventional pain procedures. We refer to
      this constellation of imaging and clinical findings as posterior ligamentous
      complex inflammatory syndrome (PLCIS).

PMID- 25577651
TI  - Environmental health hazards of e-cigarettes and their components: Oxidants and
      copper in e-cigarette aerosols.
AB  - To narrow the gap in our understanding of potential oxidative properties
      associated with Electronic Nicotine Delivery Systems (ENDS) i.e. e-cigarettes, we
      employed semi-quantitative methods to detect oxidant reactivity in disposable
      components of ENDS/e-cigarettes (batteries and cartomizers) using a fluorescein
      indicator. These components exhibit oxidants/reactive oxygen species reactivity
      similar to used conventional cigarette filters. Oxidants/reactive oxygen species
      reactivity in e-cigarette aerosols was also similar to oxidant reactivity in
      cigarette smoke. A cascade particle impactor allowed sieving of a range of
      particle size distributions between 0.450 and 2.02 MUm in aerosols from an e
      cigarette. Copper, being among these particles, is 6.1 times higher per puff than
      reported previously for conventional cigarette smoke. The detection of a
      potentially cytotoxic metal as well as oxidants from e-cigarette and its
      components raises concern regarding the safety of e-cigarettes use and the
      disposal of e-cigarette waste products into the environment.

PMID- 25577653
TI  - The clinical syndrome of bilirubin-induced neurologic dysfunction.
AB  - Clinicians have hypothesized a spectrum of minor neurologic manifestations,
      consistent with neuroanatomical reports and collectively termed as a "syndrome of
      bilirubin-induced neurologic dysfunction (BIND)," which can occur in the absence
      of classical kernicterus. The current review builds on these initial reports with
      a focus on clinical signs and symptoms that are assessed by standardized tools
      and manifest from neonatal age to childhood. These clinical manifestations are
      characterized by the following domains: (i) neuromotor signs; (ii) muscle tone
      abnormalities; (iii) hyperexcitable neonatal reflexes; (iv) variety of
      neurobehavior manifestations; (v) speech and language abnormalities; and (vi)
      evolving array of central processing abnormalities, such as sensorineural
      audiology and visuomotor dysfunctions. Concerns remain that the most vulnerable
      infants are likely to acquire BIND, either because their exposure to bilirubin is
      not identified as severe enough to need treatment or is prolonged but slightly
      below current threshold levels for intervention. Knowing that a total
      serum/plasma bilirubin (TB) level is not the most precise indicator of
      neurotoxicity, the role of expanded biomarkers or a "bilirubin panel" has yet to
      be validated in prospective studies. Future studies that correlate early "toxic"
      bilirubin exposure to long-term academic potential of children are needed to
      explore new insights into bilirubin's effect on the structural and functional
      maturation of an infant's neural network topology. 

PMID- 25577656
TI  - Bilirubin-induced neurologic dysfunction (BIND).

PMID- 25577655
TI  - Visuocortical bilirubin-induced neurological dysfunction.
AB  - This review addresses the question whether elevated levels of total serum/plasma
      bilirubin (TB) cause measurable neurological effects, specifically to
      visuocortical functioning. Past research in the area of vision and its relation
      to jaundice has taken advantage of flash visual-evoked potentials (VEPs). Using a
      steady state VEP, we developed preliminary data suggesting that children who had
      jaundice with TB levels between 10 and 25mg/dL, but who did not have kernicterus,
      have measurable changes in visual function, when compared to control infants who
      did not have jaundice. This non-invasive test offers information about vision
      thresholds, signal amplitudes, and suprathreshold changes after brain exposure to
      bilirubin. Here, we review this novel tool, the steady state VEP, and data
      suggesting that neurological changes occur in infants with moderately elevated TB
      levels. 

PMID- 25577654
TI  - Impact of hypothermia on predictors of poor outcome: how do we decide to redirect
      care?
AB  - Therapeutic hypothermia is now considered the standard of care for neonates with
      neonatal encephalopathy due to perinatal asphyxia. Outcomes following hypothermia
      treatment are favorable, as demonstrated in recent meta-analyses, but 45-50% of
      these neonates still suffer major disability or die due to global multi-organ
      injury or after redirection of care from life support due to severe brain injury.
      The ability to determine which patients are at highest risk of severe neurologic
      impairment and death and those in whom redirection of care should be considered
      is limited. This is especially true in the first few days after birth and in
      situations where the brain might be more significantly affected than other organ
      systems, making it difficult to discuss redirection of care. Clinical history,
      neurologic examination, serum biomarkers, neurophysiology [amplitude-integrated
      electroencephalography (aEEG) or EEG], near-infrared spectroscopy, and magnetic
      resonance imaging have all been studied as predictors of severe neurologic injury
      and poor outcome, although none is 100% predictive. Serial evaluation over time
      seems to be an important element to facilitate discussion regarding anticipated
      poor prognosis and decision-making for transition to comfort care. Thus far,
      brain monitoring in the form of aEEG and conventional EEG seem to be the best
      objective tools to identify the highest-risk patients. A delay or lack of
      recovery of the aEEG background during hypothermia treatment is an established
      important predictor of poor outcome (death or disability). This paper highlights
      the prognostic indicators that have been considered and focuses on aEEG as an
      important predictor of death or severe disability, which may facilitate
      conversations regarding redirection of care. 

PMID- 25577657
TI  - An atypical case of left atrial myxoma.

PMID- 25577658
TI  - Relation between heart rate recovery after exercise testing and body mass index.
AB  - INTRODUCTION: Impaired heart rate (HR) recovery after exercise testing is
      considered a predictor of cardiovascular mortality as it reflects vagus nerve
      dysfunction. OBJECTIVE: To assess the relationship between body mass index (BMI)
      and HR recovery after exercise. METHODS: We analyzed the records of 2443 patients
      of both sexes, aged between 20 and 59 years, in sinus rhythm, not using negative
      chronotropic agents and with no myocardial ischemic response to exercise testing
      carried out at a specialist clinic, between 2005 and 2011. BMI was categorized as
      normal (18.5-<25 kg/m(2)), overweight (25-<=30 kg/m(2)) or obese (>30 kg/m(2)).
      The different BMI groups were compared in terms of HR recovery after exercise,
      which was calculated as the difference between maximum HR during exercise and in
      the first minute of recovery. Recovery was considered impaired when the
      difference was <=12 bpm. RESULTS: Eighty-seven (3.6%) patients presented impaired
      recovery, which was three times more prevalent in the obese group and twice as
      prevalent in the overweight group compared with the normal group (p<0.001 and
      p=0.010, respectively). Obese patients presented higher basal HR and lower
      maximum HR, as well as reduced chronotropic reserve (p<0.001). In multivariate
      analysis, impaired HR recovery was associated with overweight (relative risk
      [RR]=1.8; p=0.035), obesity (RR=2; p=0.016), number of metabolic equivalents
      (RR=0.82; p<0.001) and resting HR (RR=1.05; p<0.001). The hazard ratio for
      hypertension was 2 (p=0.083, NS). CONCLUSION: Impaired HR recovery was associated
      with higher BMI, demonstrating that obese individuals present vagus nerve
      dysfunction.

PMID- 25577659
TI  - Prosthetic mitral valve thrombosis in pregnancy: from thrombolysis to
      anticoagulation.
AB  - INTRODUCTION: Pregnant women with mechanical prosthetic heart valves are at
      increased risk for valve thrombosis. Management decisions for this life
      threatening complication are complex. Open-heart surgery has a very high risk of
      maternal mortality and fetal loss. Bleeding and embolic risks associated with
      thrombolytic agents, the limited efficacy of thrombolysis in certain subgroups,
      and a lack of experience in the setting of pregnancy raise important concerns.
      CASE REPORT: We report a case of mitral prosthetic valve thrombosis in early
      pregnancy, which was successfully treated with streptokinase. Ten years later,
      the same patient had an uneventful pregnancy, throughout which acenocoumarol was
      maintained. CONCLUSION: With this case we review the prevention (with oral
      anticoagulant therapy) and treatment of prosthetic valve thrombosis during
      pregnancy, which is important for both obstetrician and cardiologist.

PMID- 25577660
TI  - What we don't know might hurt us.

PMID- 25577662
TI  - Register data in the evaluation and program planning of addiction treatment
      programs: using Sweden as an example.
AB  - Data from large-scale registers is often underutilized when evaluating addiction
      treatment programs. Since many programs collect register data regarding clients
      and interventions, there is a potential to make greater use of such records for
      program evaluation. The purpose of this article is to discuss the value of using
      large-scale registers in the evaluation and program planning of addiction
      treatment systems and programs. Sweden is used as an example of a country where
      register data is both available and is starting to be used in national evaluation
      and program planning efforts. The article focuses on possibilities, limitations
      and practicalities when using large-scale register data to conduct evaluations
      and program planning of addiction treatment programs. Main conclusions are that
      using register data for evaluation provides large amounts of data at low cost,
      limitations associated to the use of register data may be handled statistically,
      register data can answer important questions in planning of addiction treatment
      programs, and more accurate measures are needed to account for the diversity of
      client populations. 

PMID- 25577661
TI  - Immunological effect of administration of sequential doses of Haemophilus
      influenzae type b and pneumococcal conjugate vaccines in the same versus
      alternating limbs in the routine infant immunisation schedule: an open-label
      randomised controlled trial.
AB  - BACKGROUND: The use of different limbs for the administration of sequential doses
      of an intradermal rabies vaccine was shown to result in reduced vaccine
      immunogenicity. We aimed to assess whether this phenomenon also occurs with
      routine infant vaccines. METHODS: In this open-label, randomised, controlled
      study, eligible healthy infants 6-12 weeks of age recruited through five clinical
      trials units (four in the UK and one in Malta) were randomly assigned in a 1:1
      ratio to two vaccination groups: consistent limb or alternating limb. Infants in
      the consistent limb group received the diphtheria-tetanus-acellular pertussis
      inactived polio-Haemophilus influenzae type b combined vaccine (DTaP-IPV-Hib) at
      2, 3, and 4 months of age, and the pneumococcal conjugate vaccine (PCV13) at 2,
      4, and 12 months, all administered to the right leg. Infants in the alternating
      limb group received DTaP-IPV-Hib in the left leg at 2 months and in the right leg
      at 3 and 4 months; and PCV13 in the left leg at 2 months, in the right leg at 4
      months, and in the left arm at 12 months. All infants in both groups received the
      combined H influenzae type b and capsular group C Neisseria meningitidis tetanus
      toxoid conjugate vaccine (Hib-MenC-TT), administered in the left leg at 12
      months. Randomisation was achieved by randomly generated codes, with permuted
      block size of 30, and was stratified by study site. Group allocation was not
      masked from study staff and parents of participants after enrolment, but group
      allocation was masked from laboratory staff assessing blood samples. The current
      study was a prespecified secondary objective of a parent phase 4 trial that
      assessed the induction of immunity following varying schedules of vaccination
      with glyco-conjugate capsular group C Neisseria meningitidis (Men C) vaccines in
      infancy. The objective of the current study was to compare the immunogenicity and
      reactogenicity of vaccines delivered in either consistent or alternating limbs.
      Immunogenicity was assessed by comparing serum IgG geometric mean concentrations
      at 5, 12, 13, and 24 months, analysed per protocol. This study is registered with
      ClinicalTrials.gov, number NCT01129518. FINDINGS: Between July 5, 2010, and Aug
      1, 2013, we enrolled 509 infants and randomly allocated them to the consistent
      limb group (n=254) or the alternating limb group (n=255). Anti-H influenzae type
      b anti-polyribosylribitol phosphate IgG geometric mean concentrations were lower
      in the consistent limb group than in the alternating limb group at 5 months
      (consistent limb 0.41 MUg/mL [95% CI 0.31-0.54] vs alternating limb 0.61 MUg/mL
      [0.45-0.82]; p=0.0268) and at 12 months (0.35 MUg/mL [0.28-0.43] vs 0.50 MUg/mL
      [0.40-0.62]; p=0.0136). Anti-tetanus toxoid antibody IgG geometric mean
      concentrations were lower in the consistent limb group (1.63 IU/mL [95% CI 1.40
      1.90]) than in the alternating limb group (2.30 IU/mL [1.97-2.68]) at 13 months
      (p=0.0008) and at 24 months (0.44 IU/mL [0.37-0.52] vs 0.61 IU/mL [0.51-0.73];
      p=0.0074). Anti-pneumococcal IgG geometric mean concentrations were similar
      between both groups at all timepoints. The proportions of participants who had
      adverse events did not differ between the two groups. INTERPRETATION: Use of
      different (alternating) limbs for sequential doses of routine infant vaccines
      does not reduce, and might enhance, immunogenicity. The underlying mechanism for
      this finding warrants further research. FUNDING: NIHR Oxford Biomedical Research
      Centre and GlaxoSmithKline Biologicals.

PMID- 25577663
TI  - Mortality among a national population sentenced to compulsory care for substance
      use disorders in Sweden: descriptive study.
AB  - Sweden's compulsory addiction system treats individuals with severe alcohol and
      narcotics use disorders. Merging data from three national level register
      databases of those sentenced to compulsory care from 2001 to 2009 (n=4515), the
      aims of this study were to: (1) compute mortality rates to compare to the general
      Swedish population; (2) identify leading cause of mortality by alcohol or
      narcotics use; and (3) identify individual level characteristics associated with
      mortality among alcohol and narcotics users. In this population, 24% were
      deceased by 2011. The most common cause of death for alcohol users was physical
      ailments linked to alcohol use, while narcotics users commonly died of drug
      poisoning or suicide. Average age of death differed significantly between alcohol
      users (55.0) and narcotics users (32.5). Multivariable logistic regression
      analysis identified the same three factors predicting mortality: older age
      (alcohol users OR=1.28, narcotic users OR=1.16), gender [males were nearly 3
      times more likely to die among narcotics users (p<.000) and 1.6 times more likely
      to die among alcohol users (p<.01)] and reporting serious health problems (for
      alcohol users p<.000, for narcotics users p<.05). Enhanced program and government
      efforts are needed to implement overdose-prevention efforts and different
      treatment modalities for both narcotic and alcohol users. 

PMID- 25577664
TI  - Mouth opening and trismus in patients undergoing curative treatment for head and
      neck cancer.
AB  - This study documents mouth opening and the incidence of and factors contributing
      to trismus (<35 mm mouth opening), as well as the associated impact on quality of
      life, following curative treatment for head and neck cancer. Patient
      demographics, cancer type and location, and treatments were documented. Mouth
      opening was measured at >6 months after treatment completion. Patients rated the
      impact of mouth opening on quality of life from 0 (no effect) to 10 (greatest
      effect). The mean mouth opening in 120 patients was 40.1mm (range 11-65 mm), with
      trismus occurring in 34 (28.3%) patients. Surgery and radiotherapy, surgery and
      chemoradiotherapy, and resection and reconstruction were associated with reduced
      mouth opening. The mean effect of mouth opening on quality of life for those with
      and without trismus was 3.8 and 1.5, respectively. There was a significant
      difference between the mean effect on quality of life for patients with and
      without trismus for those patients who underwent chemoradiotherapy or combined
      surgery and radiotherapy (4.0 vs. 1.0, and 3.6 vs. 1.6 respectively). Trismus
      impacts negatively on patient quality of life. Multi-modality treatment is
      associated with decreased mouth opening, an increased incidence of trismus, and
      reduced quality of life.

PMID- 25577665
TI  - Berberis aristata combined with Silybum marianum on lipid profile in patients not
      tolerating statins at high doses.
AB  - AIM: To evaluate the effects of Berberis aristata combined with Silybum marianum
      in dyslipidemic patients intolerant to statins at high doses. METHODS: 137
      euglycemic, dyslipidemic subjects, with previous adverse events to statins at
      high doses, were enrolled. Statins were stopped for 1 month (run-in), then they
      were re-introduced at the half of the previously taken dose. At randomization,
      patients tolerating the half dose of statin, were assigned to add placebo or B.
      aristata/S. marianum 588/105 mg, 1 tablet during the lunch and 1 tablet during
      the dinner, for six months. We evaluated lipid profile and safety parameters
      variation at randomization, and after 3, and 6 months. RESULTS: B. aristata/S.
      marianum reduced fasting plasma glucose (-9 mg/dl), insulin (-0.7 MUU/ml), and
      HOMA-index (-0.35) levels compared to baseline and also to placebo. Lipid profile
      did not significantly change after 6 months since the reduction of statin dosage
      and the introduction of B. aristata/S. marianum, while it worsened in the placebo
      group both compared to placebo and with active treatment (+23.4 mg/dl for total
      cholesterol, +19.6 mg/dl for LDL-cholesterol, +23.1 mg/dl for triglycerides with
      placebo compared to B. aristata/S. marianum). We did not record any variations of
      safety parameters in nether of groups. CONCLUSIONS: B. aristata/S. marianum can
      be considered as addition to statins in patients not tolerating high dose of
      these drugs.

PMID- 25577666
TI  - Pro-/antiinflammatory dysregulation in early psychosis: results from a 1-year
      follow-up study.
AB  - BACKGROUND: Previous studies indicated a systemic deregulation of the pro
      /antiinflammatory balance in subjects after 6 months of a first psychotic
      episode. This disruption was reexamined 12 months after diagnosis to identify
      potential risk/protective factors and associations with symptom severity.
      METHODS: Eighty-five subjects were followed during 12 months and the
      determination of the same pro-/antiinflammatory mediators was carried out in
      plasma and peripheral blood mononuclear cells. Multivariate logistic regression
      analyses were used to identify risk/protective factors. Multiple linear
      regression models were performed to detect the change of each biological marker
      during follow-up in relation to clinical characteristics and confounding factors.
      RESULTS: This study suggests a more severe systemic pro-/antiinflammatory
      deregulation than in earlier pathological stages in first psychotic episode,
      because not only were intracellular components of the inflammatory response
      increased but also the majority of soluble elements. Nitrite plasma levels and
      cyclooxygenase-2 expression in peripheral blood mononuclear cells are reliable
      potential risk factors and 15d-prostaglandin-J2 plasma levels a protection
      biomarker. An interesting relationship exists between antipsychotic dose and the
      levels of prostaglandin-E2 (inverse) and 15d-prostaglandin-J2 (direct). An
      inverse relationship between the Global Assessment of Functioning scale and lipid
      peroxidation is also present. CONCLUSIONS: Summing up, pro-/antiinflammatory
      mediators can be used as risk/protection biomarkers. The inverse association
      between oxidative/nitrosative damage and the Global Assessment of Functioning
      scale, and the possibility that one of the targets of antipsychotics could be the
      restoration of the pro-/antiinflammatory balance support the use of
      antiinflammatory drugs as coadjuvant to antipsychotics.

PMID- 25577668
TI  - Future looks bright for mobile technologies in global health.

PMID- 25577669
TI  - Accelerated hypofractioned postoperative radiotherapy for prostate cancer: a
      prospective phase I/II study.
AB  - AIMS: To present the initial findings of a single institution, phase I/II study
      investigating hypofractionated radiotherapy in patients undergoing post
      prostatectomy treatment. MATERIALS AND METHODS: Patients requiring postoperative
      radiotherapy were prospectively enrolled. Dose was prescribed to the prostate bed
      with 51 Gy in 17 daily fractions. Androgen deprivation was optional. Acute and
      late gastrointestinal/genitourinary toxicity were assessed using the National
      Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 and
      quality of life was assessed using the Expanded Prostate Cancer Index Composite
      evaluation tool. Prostate-specific antigen (PSA) was evaluated at every follow
      up. RESULTS: Thirty patients were enrolled between 2009 and 2011. The median age
      was 65 years and most had Gleason 7 disease (86%) with pT2c or pT3a (82%).
      Positive margins were documented in 67% of the patients. The median pre-treatment
      PSA was 0.12 ng/ml. The median follow-up was 24 months. Overall toxicity was low,
      with >80% of patients having <= grade 1 acute toxicity in both genitourinary and
      gastrointestinal realms. Similarly, only two patients (6%) experienced grade 2/3
      late gastrointestinal/genitourinary toxicity. Quality of life scores were also
      indicative of a well-tolerated treatment. PSA failure was seen in five patients
      (17%). CONCLUSIONS: We present a hypofractionated schedule of postoperative
      prostate radiotherapy that is both well tolerated in terms of both toxicity and
      quality of life measures. Initial PSA control is encouraging. Further evaluation
      with a longer follow-up and a larger cohort is warranted.

PMID- 25577667
TI  - Protein kinase C inhibition rescues manic-like behaviors and hippocampal cell
      proliferation deficits in the sleep deprivation model of mania.
AB  - BACKGROUND: Recent studies revealed that bipolar disorder may be associated with
      deficits of neuroplasticity. Additionally, accumulating evidence has implicated
      alterations of the intracellular signaling molecule protein kinase C (PKC) in
      mania. METHODS: Using sleep deprivation (SD) as an animal model of mania, this
      study aimed to examine the possible relationship between PKC and neuroplasticity
      in mania. Rats were subjected to SD for 72 h and tested behaviorally. In
      parallel, SD-induced changes in hippocampal cell proliferation were evaluated
      with bromodeoxyuridine (BrdU) labeling. We then examined the effects of the mood
      stabilizer lithium, the antipsychotic agent aripiprazole, and the PKC inhibitors
      chelerythrine and tamoxifen on both behavioral and cell proliferation impairments
      induced by SD. The antidepressant fluoxetine was used as a negative control.
      RESULTS: We found that SD triggered the manic-like behaviors such as
      hyperlocomotion and increased sleep latency, and reduced hippocampal cell
      proliferation. These alterations were counteracted by an acute administration of
      lithium and aripiprazole but not of fluoxetine, and only a single administration
      of aripiprazole increased cell proliferation on its own. Importantly, SD rats
      exhibited increased levels of phosphorylated synaptosomal-associated protein 25
      (SNAP-25) in the hippocampus and prefrontal cortex, suggesting PKC overactivity.
      Moreover, PKC inhibitors attenuated manic-like behaviors and rescued cell
      proliferation deficits induced by SD. CONCLUSIONS: Our findings confirm the
      relevance of SD as a model of mania, and provide evidence that antimanic agents
      are also able to prevent SD-induced decrease of hippocampal cell proliferation.
      Furthermore, they emphasize the therapeutic potential of PKC inhibitors, as
      revealed by their antimanic-like and pro-proliferative properties.

PMID- 25577670
TI  - Mental health of transgender youth in care at an adolescent urban community
      health center: a matched retrospective cohort study.
AB  - PURPOSE: Transgender youth represent a vulnerable population at risk for negative
      mental health outcomes including depression, anxiety, self-harm, and suicidality.
      Limited data exist to compare the mental health of transgender adolescents and
      emerging adults to cisgender youth accessing community-based clinical services;
      the present study aimed to fill this gap. METHODS: A retrospective cohort study
      of electronic health record data from 180 transgender patients aged 12-29 years
      seen between 2002 and 2011 at a Boston-based community health center was
      performed. The 106 female-to-male (FTM) and 74 male-to-female (MTF) patients were
      matched on gender identity, age, visit date, and race/ethnicity to cisgender
      controls. Mental health outcomes were extracted and analyzed using conditional
      logistic regression models. Logistic regression models compared FTM with MTF
      youth on mental health outcomes. RESULTS: The sample (N = 360) had a mean age of
      19.6 years (standard deviation, 3.0); 43% white, 33% racial/ethnic minority, and
      24% race/ethnicity unknown. Compared with cisgender matched controls, transgender
      youth had a twofold to threefold increased risk of depression, anxiety disorder,
      suicidal ideation, suicide attempt, self-harm without lethal intent, and both
      inpatient and outpatient mental health treatment (all p < .05). No statistically
      significant differences in mental health outcomes were observed comparing FTM and
      MTF patients, adjusting for age, race/ethnicity, and hormone use. CONCLUSIONS:
      Transgender youth were found to have a disparity in negative mental health
      outcomes compared with cisgender youth, with equally high burden in FTM and MTF
      patients. Identifying gender identity differences in clinical settings and
      providing appropriate services and supports are important steps in addressing
      this disparity.

PMID- 25577671
TI  - Exaggerated increases in blood pressure during isometric muscle contraction in
      hypertension: role for purinergic receptors.
AB  - Physical activity is a cornerstone therapy for the primary prevention and
      treatment of hypertension, which is becoming increasingly prevalent in modern
      societies. During exercise, heart rate and blood pressure (BP) increase in order
      to acutely meet the metabolic demands of the working skeletal muscle. In
      hypertensive adults, isometric exercise-induced increases in BP are excessive,
      potentially increasing the risk of an acute cardiovascular event during or after
      physical activity. Recently, the skeletal muscle metaboreflex has emerged as a
      significant contributor to the development of aberrant cardiovascular control
      during isometric exercise in this clinical population. Our laboratory has
      conducted a series of studies characterizing the skeletal muscle metaboreflex in
      hypertensive humans. We and others have demonstrated that hypertension is
      characterized by greater increases in muscle sympathetic nerve activity and BP
      during selective activation of the metaboreflex during post-exercise muscle
      ischemia compared to the increases noted in healthy age-matched normotensive
      adults, suggesting that the skeletal muscle metaboreflex is exaggerated in human
      hypertension. The focus of this review is the skeletal muscle metaboreflex (i.e.,
      the metabolic component of the exercise pressor reflex) in hypertension, with
      particular emphasis on the potential role of purinergic receptors in mediating
      the exaggerated responses to muscle metaboreflex activation. 

PMID- 25577673
TI  - A therapy parameter-based model for predicting blood glucose concentrations in
      patients with type 1 diabetes.
AB  - In this paper, the problem of predicting blood glucose concentrations (BG) for
      the treatment of patients with type 1 diabetes, is addressed. Predicting BG is of
      very high importance as most treatments, which consist in exogenous insulin
      injections, rely on the availability of BG predictions. Many models that can be
      used for predicting BG are available in the literature. However, it is widely
      admitted that it is almost impossible to perfectly model blood glucose dynamics
      while still being able to identify model parameters using only blood glucose
      measurements. The main contribution of this work is to propose a simple and
      identifiable linear dynamical model, which is based on the static prediction
      model of standard therapy. It is shown that the model parameters are
      intrinsically correlated with physician-set therapy parameters and that the
      reduction of the number of model parameters to identify leads to inferior data
      fits but to equivalent or slightly improved prediction capabilities compared to
      state-of-the-art models: a sign of an appropriate model structure and superior
      reliability. The validation of the proposed dynamic model is performed using data
      from the UVa simulator and real clinical data, and potential uses of the proposed
      model for state estimation and BG control are discussed. 

PMID- 25577674
TI  - Nursing students' experiences with the use of authentic assessment rubric and
      case approach in the clinical laboratories.
AB  - BACKGROUND: One current challenge for nurse educators is to examine effective
      nursing assessment tools which integrate nursing knowledge into practice.
      Authentic assessment allows nursing students to apply knowledge to real-life
      experiences. Contextualized cases have engaged students for preparation of
      diverse clinical situations and develop critical thinking skills. AIM: This study
      aimed to explore nursing students' experiences and learning outcomes with the use
      of an authentic assessment rubric and a case approach. METHODS: An exploratory
      qualitative approach using focus-group discussions and an open-ended survey was
      adopted. Sixteen nursing students participated in three focus-group discussions
      and 39 nursing students completed an open-ended survey. RESULTS: Nursing students
      noted that an authentic assessment rubric with a case approach provided clarity
      for their learning goals; built confidence; developed knowledge, skill
      competencies and critical thinking skills; increased awareness of caring
      attributes and communication skills; and enriched and extended learning through
      self-, peer- and teacher-assessments. CONCLUSIONS: These findings provide rich
      insights for nurse educators and curriculum developers in the use of an authentic
      assessment rubric and a case approach in nursing education.

PMID- 25577672
TI  - Use of Monsel solution to treat obstetrical hemorrhage: a review and comparison
      to other topical hemostatic agents.
AB  - Peripartum hemorrhage accounts for 8% of maternal deaths in the United States,
      and nearly 27% worldwide. A growing need exists for tactics to spare morbidity
      given a rise of abnormal placentation that contributes to excessive blood loss at
      the time of delivery. Approaches such as compression sutures, balloon tamponade,
      and pelvic artery embolization are not without side effects and potential
      implications for future fertility. The use of topical hemostatic agents has
      become widespread in gynecologic and obstetric surgery despite a paucity of
      distinct studies in the field, and may allow providers to increasingly avoid
      cesarean hysterectomy. A variety of topical hemostatic agents exist along a wide
      cost continuum, each characterized by specific efficacy, advantages, drawbacks,
      and often gaps in long-term data to support safety and impact on future
      fertility. Herein, we comprehensively review these agents and illustrate a
      nontraditional use of Monsel solution applied directly to the placental bed in a
      case of focal placenta accreta. This ultimately contributed to successful uterine
      preservation with no known adverse sequelae. Monsel solution may have a role in
      establishing hemostasis in the setting of abnormal placentation, and may be a
      particularly attractive alternative in resource-poor nations. 

PMID- 25577675
TI  - Interactions between parasitic infections and reproductive efficiency in sheep.
AB  - This review article summarises the many reports in the literature, confirming
      that, in sheep, parasitic infections can adversely affect reproductive
      efficiency; examples, which refer to all parts of the reproductive cycle of
      sheep, are as follows: trichostrongylosis in ewe-lambs (which can lead to delayed
      attainment of puberty), myiosis of the prepuce (which can cause impediment of
      mating), chorioptic mange or trypanosomosis in rams (which can lead to testicular
      degeneration or azoospermia, respectively), trypanosomosis or sarcoptic mange in
      pre-conceptual ewes (which can lead to poor conception rates or reduced number of
      ovulations, respectively), toxoplasmosis or neosporosis in pregnant ewes (which
      are causes of abortion), trichostrongylosis or trematode infections in lactating
      ewes (which can cause reduction of milk yield and can be a risk factor for
      mastitis, respectively), cryptosporidiosis in newborn lambs (which can be a cause
      of deaths), coccidiosis in growing pre-weaned lambs (which can cause suboptimal
      growth rate). In other cases, the reproductive status of the animal can influence
      the parasitic infection; examples are as follows: the increase in faecal
      parasitic output during the peri-parturient period (as a consequence of the peri
      parturient relaxation of immunity), the heavier trichostrongylid infections of
      twin lambs compared to lambs from single parities (as a consequence of
      developmental origin issues in twin lambs). All the above examples support the
      idea of presence of interactions between parasitic infections and reproductive
      efficiency in sheep. 

PMID- 25577677
TI  - Measuring general animal health status: Development of an animal health
      barometer.
AB  - The development of an animal health barometer, an instrument to measure the
      general health of the Belgian livestock population on a yearly basis and to
      monitor its evolution over time, is described. The elaboration of a set of 13
      animal health indicators (AHIs) as the basis for the animal health barometer is
      discussed. These indicators were weighted by experts - including scientists,
      policy makers and agro-industrial representatives - to determine their relative
      weight in the barometer. The result of the barometer is expressed as a comparison
      with a previous year. Based on the results of the 13 AHIs, it is concluded that
      general animal health in Belgium shows a positive evolution since 2008. The
      animal health barometer provides a composite view of the status of livestock
      health in Belgium and is a tool to communicate in an intelligible, comprehensible
      manner on aspects of animal health to consumers and professional stakeholders in
      the animal production and food chain. Together with the food safety barometer
      (Baert et al., 2011. Food Res. Int. 44, 940) and the plant health barometer
      (Wilmart et al., 2014. Eur. J. Plant Pathol. doi: 10.1007/s10658-014-0547-x), the
      animal health barometer is one of the three instruments to provide a holistic
      view on the overall status of the safety of the food chain in Belgium. 

PMID- 25577676
TI  - Integrated control of an acaricide-resistant strain of the cattle tick
      Rhipicephalus microplus by applying Metarhizium anisopliae associated with
      cypermethrin and chlorpyriphos under field conditions.
AB  - The efficacy of the fungus Metarhizium anisopliae to control ticks has been shown
      in several in vitro experiments. However, few studies have been undertaken in
      field conditions in order to demonstrate the applicability of its use as a
      biological control of ticks and its combination with chemical acaricides. The aim
      of the present study was to evaluate the efficacy of M. anisopliae to control an
      acaricide-resistant strain of Rhipicephalus microplus under laboratory and field
      conditions. First, the compatibility of M. anisopliae strain (TIS-BR03) with
      commercial acaricides and its potential to control the cattle tick were evaluated
      in vitro. In general, acaricide treatments had mild effects on fungus viability.
      In the field experiment, the median of treatment efficacy with acaricide only, M.
      anisopliae only and combination of M. anisopliae with acaricide were 71.1%, 56.3%
      and 97.9%, respectively. There is no statistical difference between groups
      treated with M. anisopliae and acaricide alone. Thus, in this work we have
      demonstrated the applicability of M. anisopliae use associated or not with
      chemical acaricides on field conditions in order to control an acaricide
      resistant strain of the cattle tick R. microplus. 

PMID- 25577678
TI  - From network analysis to risk analysis--An approach to risk-based surveillance
      for bovine tuberculosis in Minnesota, US.
AB  - Bovine tuberculosis (bTB) was first detected in 2005 in cattle in northwestern
      Minnesota (MN) through slaughter surveillance. By the end of 2008, 12 cattle
      herds were infected with bTB, and the main cause for infection was determined to
      be the movement of infected animals between herds. Bovine tuberculosis was
      contained in a smaller area in northwestern Minnesota classified as modified
      accredited (MA), corresponding to a prevalence inferior to 0.1% in cattle. From
      January 2008 to 2011, all cattle movements within the bTB MA were recorded
      electronically. The primary objectives of this study were to characterize cattle
      movements within this region and identify cattle herds with higher risk of bTB
      introduction based on network parameters and known risk factors from the
      published literature. During the period that data was collected, 57,460 cattle
      were moved in 3762 movements corresponding to permits issued to 682 premises,
      mostly representing private farms, sale yards, slaughter facilities and county or
      state fairs. Although sale yards represented less than 2% of the premises
      (nodes), 60% of the movements were to or from a sale yard. The network showed an
      overall density of 0.4%, a clustering coefficient of 14.6% and a betweenness
      centralization index of 12.7%, reflecting the low connectivity of this cattle
      network. The degree distribution showed that 20% of nodes performed 90% of the
      movements. Farms were ranked based on the total risk score and divided into high,
      medium, and low risk groups based on the score and its variability. The higher
      risk group included 14% (n=50) of the farms, corresponding to 80% of the
      cumulative risk for the farms in the bTB area. This analysis provides a baseline
      description about the contact structure of cattle movements in an area previously
      infected with bTB and develops a framework for a targeted surveillance approach
      for bTB to support future surveillance decisions. 

PMID- 25577679
TI  - [Restructuring the healthcare system: redesigning based on needs].
AB  - The main task of a healthcare system is the provision of the healthcare services
      demanded by the population. These needs are mostly defined by the epidemiological
      status, which has been significantly changed during the last century. Due to
      development of medical science and technology, the main health problems in modern
      industrial societies are related to chronic diseases rather than infectious
      diseases occurring at the beginning of the 20th century. However, healthcare
      services provided by health institutions are still reactive, formed as reactions
      to current conditions, and they are hardly suited to requirements related to
      chronic diseases. This paper outlines international and national healthcare
      models and their shortcomings, and it traces novel paths of a future solution.
      The structure of the optimal model is suited to systematically produce the
      services which are needed by the population, decisively in the case of chronic,
      non communicable diseases. This can significantly relieve the expensive,
      technology-based reactive care system, nevertheless, it can provide efficient
      services in case of tertiary prevention. The configuration of this system is
      cheap, there is no need of significant infrastructure, but needs massive human
      resource, so that it can be rationally designed in parallel with the constriction
      of the reactive care system.

PMID- 25577680
TI  - [Perspectives in the management of congenital heart defects in adult patients].
AB  - Due to improving results in congenital heart surgery, the number of adult
      patients with congenital heart defect is increasing. The question is: what kind
      of problems can be managed in this patient-group? The authors review the
      different problems of management of congenital heart defects in adults based on
      national and international literature data. Simple defects recognised in adults,
      postoperative residual problems, changing of small grafts and valves, correction
      of primary or operated coarctation aortae can be usually managed without
      problems. A very close follow-up is necessary to establish the correct period for
      heart transplantation in patients with transposition of great arteries with
      Senning/Mustard operation, and univentricular heart corrected with "Fontan
      circulation" type surgical procedure. The authors conclude that although the
      number of patients increases, only a few congenital heart diseases may cause
      problems. It seems important (1) to monitor asymptomatic patient who underwent
      operation (Fallot-IV, Ross procedure, etc.), (2) follow up regularly patients who
      underwent Senning/Mustard procedure (magnetic resonance imaging,
      echocardiography, brain natriuretic peptide measurement), (3) define the proper
      period of preparation for heart transplantation of patients with a univentricular
      heart, with special attention to the possibility of multiorgan (lung, liver,
      etc.) failure. Due to the improvement of foetal diagnosis of congenital heart
      defects, the number of patients with complex congenital heart defects is
      decreasing. The standard management of these patients could be primary heart
      transplantation in infancy.

PMID- 25577681
TI  - [Extranodal lymphomas in adults in Szabolcs-Szatmar-Bereg county, Hungary.
      Analysis of 30 years' epidemiologic data].
AB  - INTRODUCTION: In their previous work, the authors reported 27-year' findings on
      the epidemiology of extranodal lymphomas in Szabolcs-Szatmar-Bereg county,
      Hungary. There are no other studies on this topic available in Hungary. AIM: The
      aim of this study was to analyse in detail the epidemiologic data of patients
      with non-Hodgkin's lymphoma who were recorded in the leukaemia/lymphoma registry
      of Szabolcs-Szatmar-Bereg county during a 30-year period, to compare the main
      epidemiologic features of the extranodal and nodal forms, and compare the results
      with data reported in the international literature. METHOD: Between January 1,
      1983 and December 31, 2012, 1123 adult patients with newly diagnosed non
      Hodgkin's lymphoma were recorded in the leukaemia/lymphoma registry of Szabolcs
      Szatmar-Bereg county. Of those, 347 patients suffered from extranodal, and 776
      patients from nodal form of non-Hodgkin's lymphoma. The authors compared the
      incidence of the extranodal and nodal forms, the age and sex distribution of
      patients, the ratio of B- and T-cell, as well as the indolent and aggressive
      forms, the geographic distribution and the association with carcinomas. In
      addition, they studied the occurrence of familial appearance and the localisation
      of extranodal forms. RESULTS: The occurrence of non-Hodgkin's lymphomas indicated
      an increasing tendency in their county. This tendency was true for both the
      extranodal and nodal forms, but it was more remarkable in the extranodal form of
      lymphomas. They found no substantial difference between the main epidemiologic
      features of the two forms. The gastrointestinal tract was the most frequent site
      of presentation for extranodal lymphomas. CONCLUSIONS: These observations are in
      line with data reported in the international literature. The data are essentially
      similar to those published in populations from Western European countries and the
      United States.

PMID- 25577682
TI  - [Knowledge and perception of medical students about infertility].
AB  - INTRODUCTION: The effectiveness of fertility treatments is influenced by the
      health care professionals' knowledge regarding infertility as well as their
      empathy. AIM: The aim of the study was to examine infertility-related knowledge
      and perceptions of emotional and mind/body consequences of infertility among
      medical students. METHODS: A questionnaire design was used. Data were obtained
      from 112 medical university students (76 women, 36 men) who participated
      involuntary and compensation-free. RESULTS: Medical students' knowledge
      concerning infertility proved to be incomplete and ambiguous. Subjects
      underestimated the presence of mind/body and emotional symptoms caused by
      infertility in men particularly, and overestimated some emotional concerns in
      women, e.g. sadness. CONCLUSIONS: Medical students have gaps in their subject
      specific knowledge, so that they need more (even practical) information regarding
      infertility during their studies. Students' conceptions about emotional and
      physical consequences of infertility are distorted by stereotypes. The risk of
      these biases is that it could make it difficult to perceive patients in a non
      distorted way, especially infertile male patients.

PMID- 25577683
TI  - [Genetic testing in hereditary spastic paraplegia].
AB  - INTRODUCTION: Hereditary spastic paraplegia is the overall term for clinically
      and genetically diverse disorders characterized with progressive and variable
      severe lower extremity spasticity. The most common causes of autosomal dominantly
      inherited hereditary spastic paraplegias are different mutations of the spastin
      gene with variable incidence in different ethnic groups, ranging between 15-40%.
      Mutations in the spastin gene lead to loss of spastins function, causing
      progressive neuronal failure, which results in axon degeneration finally. AIM:
      The molecular testing of spastin gene is available in the institution of the
      authors since January, 2014. The experience gained with the examination of the
      first eleven patients is described in this article. METHOD: After polymerase
      chain reaction, Sanger sequencing was performed to examine the 17 exons of the
      spastin gene. Multiplex ligation-dependent probe amplification was performed to
      detect greater rearrangements in the spastin gene. Eight of the patients were
      examined in the genetic counseling clinic of the authors and after detailed
      phenotype assessment spastin gene testing was obtained. The other three patients
      were referred to the laboratory from different outpatient clinics. RESULTS: Out
      of the 11 examined patients, four different pathogenic mutations were found in 5
      patients. CONCLUSIONS: The first Hungarian data, gained with the examination of
      spastin gene are presented in this article. The five patients, in whom mutations
      were detected, represent 45.5% of all tested patients with hereditary spastic
      paraplegia, which is similar to those published in the international literature.
      Molecular testing and subsequent detailed genotype-phenotype correlations of the
      Hungarian patients may serve valuable new information about the disease, which
      later on may influence our therapeutic possibilities and decisions.

PMID- 25577684
TI  - [Dr. Janos Ivanyi (1924-2014)].

PMID- 25577687
TI  - Biowaste home composting: experimental process monitoring and quality control.
AB  - Because home composting is a prevention option in managing biowaste at local
      levels, the objective of the present study was to contribute to the knowledge of
      the process evolution and compost quality that can be expected and obtained,
      respectively, in this decentralized option. In this study, organized as the
      research portion of a provincial project on home composting in the territory of
      Pesaro-Urbino (Central Italy), four experimental composters were first initiated
      and temporally monitored. Second, two small sub-sets of selected provincial
      composters (directly operated by households involved in the project) underwent
      quality control on their compost products at two different temporal steps. The
      monitored experimental composters showed overall decreasing profiles versus
      composting time for moisture, organic carbon, and C/N, as well as overall
      increasing profiles for electrical conductivity and total nitrogen, which
      represented qualitative indications of progress in the process. Comparative
      evaluations of the monitored experimental composters also suggested some
      interactions in home composting, i.e., high C/N ratios limiting organic matter
      decomposition rates and final humification levels; high moisture contents
      restricting the internal temperature regime; nearly horizontal phosphorus and
      potassium evolutions contributing to limit the rates of increase in electrical
      conductivity; and prolonged biowaste additions contributing to limit the rate of
      decrease in moisture. The measures of parametric data variability in the two sub
      sets of controlled provincial composters showed decreased variability in
      moisture, organic carbon, and C/N from the seventh to fifteenth month of home
      composting, as well as increased variability in electrical conductivity, total
      nitrogen, and humification rate, which could be considered compatible with the
      respective nature of decreasing and increasing parameters during composting. The
      modeled parametric kinetics in the monitored experimental composters, along with
      the evaluation of the parametric central tendencies in the sub-sets of controlled
      provincial composters, all indicate that 12-15 months is a suitable duration for
      the appropriate development of home composting in final and simultaneous
      compliance with typical reference limits.

PMID- 25577686
TI  - Mechanisms of thrombogenesis in polycythemia vera.
AB  - Thrombotic and cardiovascular events are among the leading causes of death for
      patients with polycythemia vera (PV), and thrombosis history is a key criterion
      for patient risk stratification and treatment strategy. Little is known, however,
      about mechanisms of thrombogenesis in patients with PV. This report provides an
      overview of thrombogenesis pathophysiology in patients with PV and elucidates the
      roles of conventional and nonconventional thrombotic risk factors. In addition to
      several conventional risk factors for thrombosis, clinical data have implicated
      increased hematocrit and red blood cell adhesiveness, activated platelets,
      leukocytosis, and elevated JAK2(V617F) allele burden in patients with PV.
      Furthermore, PV-related inflammation may exacerbate thrombogenesis through varied
      mechanisms, including endothelial damage, inhibition of natural anticoagulant
      pathways, and secretion of procoagulant factors. These findings suggest a direct
      link between myeloproliferation and thrombogenesis in PV, which is likely to
      provide new opportunities for targeted antithrombotic interventions aimed at
      decreasing PV-related morbidity and mortality. 

PMID- 25577688
TI  - Effect of recreational diving on Patagonian rocky reefs.
AB  - Tourism has grown considerably in the last decades, promoting activities such as
      recreational SCUBA diving that may affect marine benthic communities. In Puerto
      Madryn, Patagonia Argentina, sub-aquatic tourism areas (STA) receive about 7,000
      divers per year. Diving is concentrated on a few small rocky reefs and 50% of the
      dives occur in summer. In this work, we evaluated the effect of recreational
      diving activities on benthic communities and determined whether diving causes a
      press (long-term) or a pulse (short-term) response. We quantified the percentage
      cover of benthic organisms and compared benthic assemblage structure and
      composition between two sites with contrasting usage by divers, 'highly
      disturbed' and 'moderately disturbed' sites, and two 'control' sites with similar
      physical characteristics but no diving activity, twice before and after the
      diving peak in summer. We found differences in benthic assemblage structure
      (identity and relative abundance of taxa) and composition (identity only) among
      diving sites and controls. These differences were consistent before and after the
      peak of diving in summer, suggesting that recreational diving may produce a press
      impact on overall benthic assemblage structure and composition in these STA. At
      the moderately disturbed site, however, covers of specific taxa, such as some key
      habitat-forming or highly abundant species, usually differed from those in
      controls only immediately after summer, after which they begun to resemble
      controls, suggesting a pulse impact. Thus, STA in Golfo Nuevo seem to respond
      differently to disturbances of diving depending on the usage of the sites. This
      information is necessary to develop sound management strategies in order to
      preserve local biodiversity. 

PMID- 25577689
TI  - Minimizing N2O emissions and carbon footprint on a full-scale activated sludge
      sequencing batch reactor.
AB  - A continuous, on-line quantification of the nitrous oxide (N2O) emissions from a
      full-scale sequencing batch reactor (SBR) placed in a municipal wastewater
      treatment plant (WWTP) was performed in this study. In general, N2O emissions
      from the biological wastewater treatment system were 97.1 +/- 6.9 g N2O-N/Kg
      [Formula: see text] consumed or 6.8% of the influent [Formula: see text] load. In
      the WWTP of this study, N2O emissions accounted for over 60% of the total carbon
      footprint of the facility, on average. Different cycle configurations were
      implemented in the SBR aiming at reaching acceptable effluent values. Each cycle
      configuration consisted of sequences of aerated and non-aerated phases of
      different time length being controlled by the ammonium set-point fixed. Cycles
      with long aerated phases showed the largest N2O emissions, with the consequent
      increase in carbon footprint. Cycle configurations with intermittent aeration
      (aerated phases up to 20-30 min followed by short anoxic phases) were proven to
      effectively reduce N2O emissions, without compromising nitrification performance
      or increasing electricity consumption. This is the first study in which a
      successful operational strategy for N2O mitigation is identified at full-scale. 

PMID- 25577690
TI  - Evaluating two concepts for the modelling of intermediates accumulation during
      biological denitrification in wastewater treatment.
AB  - The accumulation of the denitrification intermediates in wastewater treatment
      systems is highly undesirable, since both nitrite and nitric oxide (NO) are known
      to be toxic to bacteria, and nitrous oxide (N2O) is a potent greenhouse gas and
      an ozone depleting substance. To date, two distinct concepts for the modelling of
      denitrification have been proposed, which are represented by the Activated Sludge
      Model for Nitrogen (ASMN) and the Activated Sludge Model with Indirect Coupling
      of Electrons (ASM-ICE), respectively. The two models are fundamentally different
      in describing the electron allocation among different steps of denitrification.
      In this study, the two models were examined and compared in their ability to
      predict the accumulation of denitrification intermediates reported in four
      different experimental datasets in literature. The N-oxide accumulation predicted
      by the ASM-ICE model was in good agreement with values measured in all four
      cases, while the ASMN model was only able to reproduce one of the four cases. The
      better performance of the ASM-ICE model is due to that it adopts an "indirect
      coupling" modelling concept through electron carriers to link the carbon
      oxidation and the nitrogen reduction processes, which describes the electron
      competition well. The ASMN model, on the other hand, is inherently limited by its
      structural deficiency in assuming that carbon oxidation is always able to meet
      the electron demand by all denitrification steps, therefore discounting electron
      competition among these steps. ASM-ICE therefore offers a better tool for
      predicting and understanding intermediates accumulation in biological
      denitrification. 

PMID- 25577692
TI  - Effects of cadmium accumulation from suspended sediments and phytoplankton on the
      Oyster Saccostrea glomerata.
AB  - Metals are accumulated by filter feeding organisms via water, ingestion of
      suspended sediments or food. The uptake pathway can affect metal toxicity.
      Saccostrea glomerata were exposed to cadmium through cadmium-spiked suspended
      sediments (19 and 93MUg/g dry mass) and cadmium-enriched phytoplankton (1.6
      3MUg/g dry mass) and cadmium uptake and effects measured. Oysters accumulated
      appreciable amounts of cadmium from both low and high cadmium spiked suspended
      sediment treatments (5.9+/-0.4MUg/g and 23+/-2MUg/g respectively compared to
      controls 0.97+/-0.05MUg/g dry mass). Only a small amount of cadmium was
      accumulated by ingestion of cadmium-enriched phytoplankton (1.9+/-0.1MUg/g
      compared to controls 1.2+/-0.1MUg/g). In the cadmium spiked suspended sediment
      experiments, most cadmium was desorbed from sediments and cadmium concentrations
      in S. glomerata were significantly related to dissolved cadmium concentrations (4
      21MUg/L) in the overlying water. In the phytoplankton feeding experiment cadmium
      concentrations in overlying water were <0.01MUg/L. In both exposure experiments,
      cadmium-exposed oysters showed a significant reduction in total antioxidant
      capacity and significantly increased lipid peroxidation and percentage of
      destabilised lysosomes. Destabilised lysosomes in the suspended sediments
      experiments also resulted from stress of exposure to the suspended sediments. The
      study demonstrated that exposure to cadmium via suspended sediments and to low
      concentrations of cadmium through the ingestion of phytoplankton, can cause
      sublethal stress to S. glomerata. 

PMID- 25577691
TI  - Effects of molecular weight-dependent physicochemical heterogeneity of natural
      organic matter on the aggregation of fullerene nanoparticles in mono- and di
      valent electrolyte solutions.
AB  - Given the wide presence of heterogeneous natural organic matter (NOM) and metal
      ions (Na(+)/Ca(2+)/Mg(2+)), as well as their significant role in governing
      nanoparticle stability in aqueous environments, it is of great importance to
      understand how the molecular weight (MW)-dependent physicochemical properties of
      NOM impact fundamental transportation processes like the aggregation of
      engineered nanoparticles (ENPs) in the presence of Na(+)/Ca(2+)/Mg(2+). Here, we
      report on the aggregation behavior of a model ENP, fullerene nanoparticles (nC60)
      in the presence of five MW fractions of Suwannee River NOM (Mf-SRNOMs, separated
      by ultrafiltration techniques) and three electrolytes (NaCl, CaCl2 and MgCl2). We
      found that in all NaCl treatments and low concentration CaCl2/MgCl2 treatments,
      the enhancement of nC60 stability positively correlated with the MW of Mf-SRNOMs.
      Whereas, the stability efficiency of identical Mf-SRNOM in different electrolytes
      followed an order of NaCl > MgCl2 > CaCl2, and the enhanced attachment of nC60
      SRNOM associations was observed in high MW Mf-SRNOM (SRNOM>100 kD and SRNOM 30
      100 kD) at high concentration CaCl2/MgCl2. Our results indicate that although the
      high MW NOM with large humic-like material is the key component for stabilizing
      nC60 in monovalent electrolyte, it could play a reversed role in promoting the
      attachment of nC60, especially in long term aggregations and at high
      concentrations of divalent cations. Therefore, a detailed understanding of the
      effects of heterogeneous NOM on the aggregation of ENPs should be highly valued,
      and properly assessed against different cation species and concentrations. 

PMID- 25577693
TI  - Sorption characteristics and persistence of herbicide bispyribac sodium in
      different global soils.
AB  - The dissipation kinetics and the adsorption characteristics of bispyribac sodium,
      a pyrimidinyloxybenzoic herbicide, in 21 types of soil collected from different
      locations in the U.S., Italy, Spain, Greece, France, U.K., the Netherlands,
      Germany, and India were evaluated under laboratory conditions. The soil sorption
      study was conducted using the batch equilibrium process. The paper also
      investigated the adsorption efficiency of bispyribac sodium in the presence of
      different kinds of background electrolytes, surfactants, and different
      temperatures in two different soils. The results showed that the Freundlich
      equation fits its adsorption well, and the Freundlich adsorption constant values
      (Kf) ranged from 0.3 to 5.6 mL g(-1). Adsorption isotherms were nonlinear, with
      1/nf values <1. Bispyribac sodium adsorption by two soils increased with
      increasing electrolytes concentration using CaCl2, KCl, NH4Cl, KH2PO4 and MgCl2
      as a background electrolytes. The adsorption coefficient value decreased when
      anionic and nonionic surfactants were used at the three surfactant concentrations
      in two types of soil but increased with cationic surfactant, and temperature.
      Sorption was positively correlated with OM and negatively correlated with a soil
      pH of 5.0 to 8.1. The free energy (DeltaG) values of bispyribac sodium in the
      soils were less than 40 kJ mol(-1) and negative values were obtained. This
      indicates that the adsorption of bispyribac sodium is mainly a physical and
      spontaneous process. The GUS values were less than 2.9 in all the soil types
      studied, and the residues of bispyribac sodium were low to moderate to leacher
      (mobile) in the soil.

PMID- 25577694
TI  - Speciation of arsenic in bulk and rhizosphere soils from artisanal cooperative
      mines in Bolivia.
AB  - Soils near artisanal and small-scale gold mines (ASGM) have high arsenic (As)
      contents due to the presence of arsenopyrite in gold ores and accelerated
      accumulations due to mine wastes disposal practices and other mining activities.
      We determined the content and speciation to understand the fate and environmental
      risks of As accumulations in 24 bulk and 12 rhizosphere soil samples collected in
      the Virgen Del Rosario and the Rayo Rojo cooperative mines in the highlands of
      Bolivia. Mean total As contents in bulk and rhizosphere soils ranged from 13 to
      64 mg kg(-1) and exceeded the soil environmental quality guidelines of Canada.
      Rhizosphere soils always contained at least twice the As contents in the bulk
      soil. Elemental mapping using 4*5 MUm synchrotron-generated X-ray micro-beam
      revealed As accumulations in areas enriched with Fe. Results of As-X-ray
      Absorption Near Edge Spectroscopy (As-XANES) showed that only As(V) species was
      detectable in all samples regardless of As contents, size fractions and types of
      vegetation. Although the toxicity of As(V) is less than As(III), we suggest that
      As uptake of commonly-grazed vegetation by alpaca and llama must be determined to
      fully understand the environmental risks of high As in soils near ASGM in
      Bolivia. In addition, knowledge on the speciation of the As bio-accessible
      fraction will provide another useful information to better understand the fate
      and transfer of As from soils into the food chain in environments associated with
      the ASGM in Bolivia and other parts of the world.

PMID- 25577695
TI  - Legacy source of mercury in an urban stream-wetland ecosystem in central North
      Carolina, USA.
AB  - In the United States, aquatic mercury contamination originates from point and non
      point sources to watersheds. Here, we studied the contribution of mercury in
      urban runoff derived from historically contaminated soils and the subsequent
      production of methylmercury in a stream-wetland complex (Durham, North Carolina),
      the receiving water of this runoff. Our results demonstrated that the mercury
      originated from the leachate of grass-covered athletic fields. A fraction of
      mercury in this soil existed as phenylmercury, suggesting that mercurial anti
      fungal compounds were historically applied to this soil. Further downstream in
      the anaerobic sediments of the stream-wetland complex, a fraction (up to 9%) of
      mercury was converted to methylmercury, the bioaccumulative form of the metal.
      Importantly, the concentrations of total mercury and methylmercury were reduced
      to background levels within the stream-wetland complex. Overall, this work
      provides an example of a legacy source of mercury that should be considered in
      urban watershed models and watershed management. 

PMID- 25577696
TI  - Assessment of arsenic in Australian grown and imported rice varieties on sale in
      Australia and potential links with irrigation practises and soil geochemistry.
AB  - Chronic dietary exposure to arsenic, particularly the inorganic forms (defined as
      elemental arsenic, predominantly As(3+) and As(5+), and all its inorganic
      compounds except arsine), is a matter of concern for human health. Ingestion of
      arsenic usually occurs via contaminated water but recent studies show there is
      also a risk of exposure from food, particularly Asian rice (Oryza sativa).
      Australia is a rice growing country, contributing around 2% of the world rice
      trade, and a large proportion of the population consumes rice regularly. In the
      present study we investigated concentrations of arsenic in both Australian grown
      and imported rice on sale in Australia and examined the potential links with
      irrigation practises and soil geochemistry. The results indicated a wide spread
      of arsenic levels of 0.09-0.33 mg kg(-1), with Australian grown Arborio and sushi
      varieties of O. sativa containing the highest mean value of ~0.22 mg kg(-1).
      Arsenic levels in all samples were below the 1 mg kg(-1) limit set by Food
      Standards Australia New Zealand.

PMID- 25577697
TI  - Cr(VI) reduction by gluconolactone and hydrogen peroxide, the reaction products
      of fungal glucose oxidase: Cooperative interaction with organic acids in the
      biotransformation of Cr(VI).
AB  - The Cr(VI) reducing capability of growing cells of the environmental A.
      tubingensis Ed8 strain is remarkably efficient compared to reference strains A.
      niger FGSC322 and A. tubingensis NRRL593. Extracellular glucose oxidase (GOX)
      activity levels were clearly higher in colonies developed in solid medium and in
      concentrated extracts of the spent medium of liquid cultures of the Ed8 strain in
      comparison with the reference strains. In addition, concentrated extracts of the
      spent medium of A. tubingensis Ed8, but not those of the reference strains,
      exhibited the ability to reduce Cr(VI). In line with this observation, it was
      found that A. niger purified GOX is capable of mediating the conversion of Cr(VI)
      to Cr(III) in a reaction dependent on the presence of glucose that is stimulated
      by organic acids. Furthermore, it was found that a decrease in Cr(VI) may occur
      in the absence of the GOX enzyme, as long as the reaction products gluconolactone
      and hydrogen peroxide are present; this conversion of Cr(VI) is stimulated by
      organic acids in a reaction that generates hydroxyl radicals, which may involve
      the formation of an intermediate peroxichromate(V) complex. These findings
      indicated that fungal glucose oxidase acts an indirect chromate reductase through
      the formation of Cr(VI) reducing molecules, which interact cooperatively with
      other fungal metabolites in the biotransformation of Cr(VI). 

PMID- 25577698
TI  - Removal of PAHs and pesticides from polluted soils by enhanced electrokinetic
      Fenton treatment.
AB  - In this study, electrokinetic-Fenton treatment was used to remediate a soil
      polluted with PAHs and the pesticide pyrimethanil. Recently, this treatment has
      emerged as an interesting alternative to conventional soil treatments due to its
      peculiar advantages, namely the capability of treating fine and low-permeability
      materials, as well as that of achieving a high yield in the removals of salt
      content and inorganic and organic pollutants. In a standard electrokinetic-Fenton
      treatment, the maximum degradation of the pollutant load achieved was 67%, due to
      the precipitation of the metals near the cathode chamber that reduces the electro
      osmotic flow of the system and thus the efficiency of the treatment. To overcome
      this problem, different complexing agents and pH control in the cathode chamber
      were evaluated to increase the electro-osmotic flux as well as to render easier
      the solubilization of the metal species present in the soil. Four complexing
      agents (ascorbic acid, citric acid, oxalic acid and ethylenediaminetetraacetic
      acid) in the Fenton-like treatment were evaluated. Results revealed the citric
      acid as the most suitable complexing agent. Thereby its efficiency was tested as
      pH controller by flushing it in the cathode chamber (pH 2 and 5). For the latter
      treatments, near total degradation was achieved after 27 d. Finally,
      phytotoxicity tests for polluted and treated samples were carried out. The high
      germination levels of the soil treated under enhanced conditions concluded that
      nearly complete restoration was achieved.

PMID- 25577699
TI  - Remediation and reclamation of soils heavily contaminated with toxic metals as a
      substrate for greening with ornamental plants and grasses.
AB  - Soils highly contaminated with toxic metals are currently treated as waste
      despite their potential inherent fertility. We applied EDTA washing technology
      featuring chelant and process water recovery for remediation of soil with 4037,
      2527, and 26 mg kg(-1) of Pb, Zn and Cd, respectively in a pilot scale. A high
      EDTA dose (120 mmol kg(-1) of soil) removed 70%, 15%, and 58% of Pb, Zn, and Cd,
      respectively, and reduced human oral bioaccessibility of Pb below the limit of
      quantification and that of Zn and Cd 3.4 and 3.2 times. In a lysimeters
      experiment, the contaminated and remediated soils were laid into two garden beds
      (4*1*0.15 m) equipped with lysimeters, and subjected to cultivation of ornamental
      plants: Impatiens walleriana, Tagetes erecta, Pelargonium*peltatum, and
      Verbena*hybrida and grasses: Dactylis glomerata, Lolium multiflorum, and Festuca
      pratensis. Plants grown on remediated soil demonstrated the same or greater
      biomass yield and reduced the uptake of Pb, Zn and Cd up to 10, 2.5 and 9.5
      times, respectively, compared to plants cultivated on the original soil. The
      results suggest that EDTA remediation produced soil suitable for greening.

PMID- 25577700
TI  - Management strategies in apple orchards influence earwig community.
AB  - Our aim was to assess whether different apple orchard management strategies (low
      input, organic, Integrated Pest Management (IPM)) would have an effect on
      earwigs, which are important natural enemies of apple pests. These commercial
      orchards were as well compared to abandoned orchards. The density of Forficula
      auricularia and Forficula pubescens was studied for three years in 74 orchards
      around Avignon. The pesticide usage, some orchard characteristics and two small
      scale landscape parameters were characterized. Pesticide use was significantly
      different between low-input, organic and IPM orchards with particularly
      significant differences in the number of insecticide applications (2.2, 4.9 and
      9.2 respectively). Pesticide use had a much stronger impact on earwig community
      than other characteristics. F. auricularia density was significantly lower in IPM
      orchards (0.47 individuals per tree) compared to organic, low-input and abandoned
      orchards (3.1, 4.5 and 1.6 individuals per tree, respectively). F. pubescens was
      almost absent from IPM orchards and its abundance was higher in abandoned or low
      input orchards compared to organic orchards (1.5 and 2.8 vs 0.8 individuals per
      tree). The percentage of F. pubescens in the earwig community decreased from
      abandoned (52%) to low-input (40%), organic (15%) and IPM orchards (0.5%). These
      results were confirmed by LD50 assays showing that for the two pesticides causing
      mortality close to normal application rates (chlorpyrifos-ethyl and acetamiprid),
      F. pubescens was significantly more sensitive than F. auricularia. Since earwigs
      are also easy to capture and identify, they may be useful to estimate the effects
      of management strategies and their modification in pome fruit orchards. 

PMID- 25577703
TI  - Optimizing environmental measures for landscape multifunctionality:
      effectiveness, efficiency and recommendations for agri-environmental programs.
AB  - Agri-environmental measures differ in their capacity to simultaneously enhance
      the provision of multiple ecosystem services. Multifunctional approaches are
      hampered by funding schemes that are usually administered by individual
      administrative sectors that each predominantly focus on one single environmental
      objective. Developing integrative management strategies that exploit synergies
      from implementing multifunctional measures is challenged by the need to quantify
      expected management effects on different ecosystem services. The objective of
      this paper is to compare uncoordinated versus coordinated management strategies
      in their contribution to multiple environmental objectives. We developed and
      applied a method for quantifying effectiveness, as well as spatial and cost
      efficiency with respect to four key landscape functions: erosion prevention,
      water quality conservation, climate change mitigation and safeguarding
      biodiversity. The case study area was the county of Verden, Germany. The
      following findings can be drawn: Measures for safeguarding biodiversity and
      climate change mitigation have generally high multifunctional effects, which
      makes them suitable for integrative management strategies. To make use of the
      added value of potential multifunctional measures, a spatially targeted
      allocation of agri-environmental measures is necessary. Compared to uncoordinated
      strategies, coordinated integrative management strategies either allow the
      optimization of the ratio of costs to environmental effects or an increase in the
      effects that can be achieved within an area unit. This is however, usually not
      simultaneous. Future research should seek to refine the assessment and valuation
      indicators. 

PMID- 25577702
TI  - Development of sludge-based adsorbents: preparation, characterization,
      utilization and its feasibility assessment.
AB  - The increasing generation of sludge and its subsequent treatment are very
      sensitive environmental problems. For a more stable and sustainable treatment of
      sludge, there have been many studies, including the conversion of sludge into
      sludge-based adsorbents (SBAs) for pollutants removal. In this review, current
      SBAs preparation conditions and use as adsorbent for contaminant removal in water
      treatment are summarized and discussed. Carbonization, physical activation and
      chemical activation are three common preparation methods. The controlling key
      parameters include pyrolysis temperature, dwell time, heating rate, activator and
      feedstock type. The efficacy of SBAs in contaminant adsorption depends on their
      surface area, pore size distribution, surface functional groups and ion-exchange
      capacity. It has been demonstrated that SBAs can attain high uptakes of dyes and
      metal ions due to their high cation exchange capacity; whereas the strong
      antibiotics adsorption performance of SBAs derives from high degree of
      mesoporosity. In addition, thermal treatment significantly stabilizes heavy
      metals contained in sludge. The paper also discusses the economic feasibility and
      environmental safety of preparation and application of SBAs. Further research
      will include investigations on the migration and transformation of element in
      sludge by thermal treatment, more economical and efficient chemical activation
      reagents, obtaining SBAs for designated application, combination of coagulation
      and SBAs adsorption, regeneration of SBAs and full-scale tests. 

PMID- 25577701
TI  - Progress on salt reduction in the Pacific Islands: from strategies to action.
AB  - BACKGROUND: Most populations are consuming too much salt which is the main
      contributor of high blood pressure, a leading risk factor of cardiovascular
      disease and stroke. The South Pacific Office of the World Health Organization has
      been facilitating the development of salt reduction strategies in Pacific Island
      Countries and areas (PICs). The objective of this analysis was to review progress
      to date and identify regional actions needed to support PICs and ensure they
      achieve the global target to reduce population salt intake by 30% by 2025.
      METHODS: Relevant available national food, health and non-communicable disease
      (NCD) plans from all 22 PICs were reviewed. NCD co-ordinators provided updates
      and relayed experiences through semi-structured interviews. All activities were
      systematically categorised according to an existing salt reduction framework for
      the development of salt reduction strategies. RESULTS: Salt reduction
      consultations had been held in 14 countries and final strategies or action plans
      developed in nine of these, with drafts available in a further three. Three other
      countries had integrated salt reduction into NCD strategic plans. Baseline
      monitoring of salt intake had been undertaken in three countries, salt levels in
      foods in nine countries and salt knowledge, attitude and behaviour surveys in
      four countries. Most countries were at early stages of implementation and
      identified limited resources as a barrier to action. Planned salt reduction
      strategies included work with food industry or importers, implementing regional
      salt reduction targets, reducing salt levels in school and hospital meals,
      behaviour change campaigns, and monitoring and evaluation. CONCLUSIONS: There had
      been good progress on salt reduction planning in PICs. The need for increased
      capacity to effectively implement agreed activities, supported by regional
      standards and the establishment of improved monitoring systems, were identified
      as important steps to ensure the potential cardiovascular health benefits of salt
      reduction could be fully realised in the region.

PMID- 25577704
TI  - Land management of bracken needs to account for bracken carcinogens--a case study
      from Britain.
AB  - Bracken ferns are some of the most widespread ferns in the World causing immense
      problems for land managers, foresters and rangers. Bracken is suspected of
      causing cancer in Humans due to its content of the carcinogen ptaquiloside.
      Ingestion of bracken, or food and drinking water contaminated with ptaquiloside
      may be the cause. The aim of this study was to monitor the content of
      ptaquiloside in 20 bracken stands from Britain to obtain a better understanding
      of the ptaquiloside dynamics and to evaluate the environmental implications of
      using different cutting regimes in bracken management. The ptaquiloside content
      in fronds ranged between 50 and 5790 MUg/g corresponding to a ptaquiloside load
      in the standing biomass of up to 590 mg/m(2) in mature fronds. Ptaquiloside was
      also found in the underground rhizome system (11-657 MUg/g) and in decaying
      litter (0.1-5.8 MUg/g). The amount of ptaquiloside present in bracken stands at
      any given time is difficult to predict and did not show any correlations with
      edaphic growth factors. The content of ptaquiloside turned out to be higher in
      fronds emerging after cutting compared to uncut fronds. Environmental risk
      assessment and bracken management must therefore be based on actual and site
      specific determinations of the ptaquiloside content. Care must be taken to avoid
      leaching from cut ferns to aquifers and other recipients and appropriate
      precautionary measures must be taken to protect staff from exposure to bracken
      dust.

PMID- 25577705
TI  - The effect of sparging rate on transmembrane pressure and critical flux in an
      AnMBR.
AB  - Anaerobic membrane bioreactors (AnMBRs) have been shown to be successful units
      for the treatment of low strength wastewaters, however, the issue of membrane
      fouling is still a major problem in terms of economic viability. Biogas sparging
      has been shown to reduce fouling substantially, and hence this study monitored
      the effect of biogas sparging rate on an AnMBR. The critical flux under a
      sparging rate of 6 l per minute (LPM) was found to be 11.8 l m(-2) h(-1) (LMH),
      however, membrane hysteresis was found to have an effect on the critical flux,
      and where the AnMBR had previously been operated with a 2 LPM sparging rate, the
      critical flux fell to 7.2 LMH. The existence of a "critical sparging rate" was
      also investigated under the condition that 'there exists a sparging rate beyond
      which any further decrease in sparging rate will cause a dramatic rise in TMP'.
      For an AnMBR operating at a flux of 7.2 LMH the critical sparging rate was found
      to be 4 LPM.

PMID- 25577706
TI  - Categories, concepts, and conditioning: how humans generalize fear.
AB  - During the past century, Pavlovian conditioning has served as the predominant
      experimental paradigm and theoretical framework to understand how humans learn to
      fear and avoid real or perceived dangers. Animal models for translational
      research offer insight into basic behavioral and neurophysiological factors
      mediating the acquisition, expression, inhibition, and generalization of fear.
      However, it is important to consider the limits of traditional animal models when
      applied to humans. Here, we focus on the question of how humans generalize fear.
      We propose that to understand fear generalization in humans requires taking into
      account research on higher-level cognition such as category-based induction,
      inferential reasoning, and representation of conceptual knowledge. Doing so will
      open the door for productive avenues of new research. 

PMID- 25577707
TI  - Synthesis and evaluation of multi-functional NO-donor/insulin-secretagogue
      derivatives for the treatment of type II diabetes and its cardiovascular
      complications.
AB  - Although there is a significant effort in the discovery of effective therapies to
      contrast both the pathological endocrine and metabolic aspects of diabetes and
      the endothelial dysfunction associated with this disease, no hypoglycemic drug
      has been proven to defeat the cardiovascular complications associated with type
      II diabetes. The aim of this research was to design new compounds exhibiting a
      double profile of hypoglycemic agents/NO-donors. The synthesis of molecules
      obtained by the conjunction of NO-donor moieties with two oral insulin
      secretagogue drugs (repaglinide and nateglinide) was reported. NO-mediated
      vasorelaxing effects of the synthesized compounds were evaluated by functional
      tests on isolated endothelium-denuded rat aortic rings. The most potent molecule
      (4) was tested to evaluate the hypoglycemic and the anti-ischemic
      cardioprotective activities. This study indicates that 4 should represent a new
      insulin-secretagogue/NO-donor prodrug with an enhanced cardiovascular activity,
      which may contrast the pathological aspects of diabetes and endowed of
      cardioprotective activity. 

PMID- 25577708
TI  - Perspective: Challenges and opportunities in TB drug discovery from phenotypic
      screening.
AB  - Tuberculosis poses a major global health problem and multi-drug resistant strains
      are increasingly prevalent. Hence there is an urgent need to discover new TB
      drugs. Cell based phenotypic screening represents a powerful approach to identify
      anti-mycobacterial compounds and elucidate novel targets. Three high throughput
      phenotypic screens were performed at NITD against mycobacterium. Hits were
      identified and chemical series selected for optimisation. This produced compounds
      with good in vitro anti-mycobacterial activity and pharmacokinetic properties.
      Some compounds displayed oral activity in mouse efficacy models of TB. Herein, we
      review the TB discovery efforts at NITD and share experiences in optimisation of
      phenotypic hits, describing challenges encountered and lessons learned. We also
      offer perspectives to facilitate future selection and advancement of phenotypic
      hits. 

PMID- 25577709
TI  - Evaluation of two novel antioxidants with differential effects on curcumin
      induced apoptosis in C2 skeletal myoblasts; involvement of JNKs.
AB  - Excessive levels of reactive oxygen species (ROS) result in numerous pathologies
      including muscle disorders. In essence, skeletal muscle performance of daily
      activities can be severely affected by the redox imbalances occurring after
      muscular injuries, surgery, atrophy due to immobilization, dystrophy or eccentric
      muscle contraction. Therefore, research on the potential beneficial impact of
      antioxidants is of outmost importance. In this context, aiming at further
      exploring the mechanisms of action of our newly synthesized antioxidant compounds
      (AK1 and AK2) in a skeletal muscle experimental setting, we initially
      investigated their scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and
      subsequently assessed their effect on the viability of C2 skeletal myoblasts in
      the presence of two pro-oxidants: H2O2 and curcumin (MTT assay). Interestingly,
      while both compounds reversed the detrimental effect of H2O2, only AK2 was
      cytoprotective in curcumin-treated C2 cells. We next confirmed the immediate
      activation of extracellular signal-regulated kinases (ERKs) and the more delayed
      activation profile of c-Jun NH2-terminal kinases (JNKs) in C2 skeletal myoblasts
      exposed to curcumin, by Western blotting. In correlation with the aforementioned
      results, only AK2 blocked the curcumin-induced activation of JNKs pathway.
      Furthermore, JNKs were revealed to mediate curcumin-induced apoptosis in C2 cells
      and only AK2 to effectively suppress it (by detecting its effect on poly(ADP
      ribose) polymerase fragmentation). Overall, we have shown that two similar in
      structure novel antioxidants confer differential effects on C2 skeletal myoblasts
      viability under oxidative stress conditions. This result may be attributed to
      these antioxidants respective diverse mode of interaction with the signaling
      effectors involved in the observed responses. Future studies should further
      evaluate the mechanism of action of these compounds in order to support their
      potential application in therapeutic protocols against ROS-related muscle
      disorders. 

PMID- 25577711
TI  - Investigation of fatty acid conjugates of 3,5-bisarylmethylene-4-piperidone
      derivatives as antitumor agents and human topoisomerase-IIalpha inhibitors.
AB  - A series of five 3,5-bisarylidene-4-piperidones designed as analogs of curcumin
      and their twenty five fatty acid conjugates were synthesized as candidate
      anticancer agents. The fatty acid conjugates were designed for efficient delivery
      of these compounds at the targeted cancer sites. The cytostatic potential of
      these compounds was evaluated against three representative cancer cell lines
      namely murine leukemic L1210 cells, and human T-lymphocyte CEM cells and cervical
      HeLa cells. Most compounds were found to exhibit significant anti-cancer activity
      in vitro. QSAR studies indicated electrophilicity of these compounds towards
      cellular nucleophiles may have a key role to play in their cytostatic activity.
      Representative compounds were also tested for topoisomerase IIalpha inhibitory
      potential, which indicated strong catalytic inhibition of the enzyme in vitro.
      The data showed that the fatty acid conjugates also possessed robust antioxidant
      activity in multiple analyses. This study also indicated that these compounds
      prompted significantly lower cellular damage in human fibroblasts than a
      currently used cancer drug sorafenib in vitro. The wide spectrum of anticancer
      action, supplemented with antioxidant potential along with non-toxic
      manifestations, certainly augment the anticancer candidacy of the novel fatty
      acid conjugates. 

PMID- 25577710
TI  - Design and synthesis of a novel series of histamine H3 receptor antagonists
      through a scaffold hopping strategy.
AB  - Lead compounds 5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl-[1,3']bipyrrolidinyl-1'
      yl)-phenyl]-benzamide (1), tetrahydro-pyran-4-carboxylic acid [((2S,3'S)-2-methyl
      [1,3']bipyrrolidinyl-1'-yl)-phenyl]-amide (2), and 3,5-dimethyl-isoxazole-4
      carboxylic acid [((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenyl]-amide (3)
      discovered in our laboratory, displayed high histamine H3 receptor (H3R)
      affinity, good selectivity and weak human Ether-a-go-go-Related Gene (hERG)
      channel affinity with desirable overall physico-chemical and pharmacokinetic (PK)
      profiles. Herein, we describe the design and synthesis of a novel series of H3R
      antagonists utilizing a scaffold hopping strategy. Further structure-activity
      relationship (SAR) studies of the series culminated in the identification of
      ((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-naphthalene-2-carboxylic acid
      (tetrahydro-pyran-4-yl)-amide (4c) and -[4-((2S,3'S)-2-methyl
      [1,3']bipyrrolidinyl-1'-yl)-phenyl]-N-(tetrahydro-pyran-4-yl)-acetamide (4d),
      which exhibited good H3R affinity in vitro, good selectivity, and desirable PK
      properties. Compounds 4c and 4d were also assessed in cardiac safety experiments.
      In particular, the effects of the compounds on action potentials recorded from
      ventricular myocytes isolated from guinea pigs were used to screen compounds that
      not only displayed a low affinity towards hERG channel, but also had lower
      interference with other cardiac ion channels. Compound 4c did not alter the major
      parameters in this model system at ?10 MUM, and no significant induction of any
      major haemodynamic effect when intravenously administered at 3mg/kg dose to
      anaesthetized mongrel dogs. Compound 4c is a new promising lead as orally potent
      and selective H3R antagonist belonging to a distinct structural class.

PMID- 25577712
TI  - Validation of a score for the early diagnosis of anastomotic leakage following
      elective colorectal surgery.
AB  - INTRODUCTION-AIM: Anastomotic leakage (AL) is the most feared complication after
      colorectal surgery. Its prognosis is related to early recognition and post
      operative management and should be based on the concept of "failure to rescue".
      The aim of the present study was to validate the "DULK" diagnostic score for AL,
      developed in The Netherlands. MATERIAL AND METHOD: From June 2012 to June 2013,
      100 consecutive patients were included in a prospective study according to the
      post-operative care protocol developed by den Dulk et al. The score is based on
      several laboratory and clinical items recorded daily. RESULTS: Among the 100
      patients, 12 developed a post-operative AL (12%) with a specific mortality rate
      of 16.6% (2 patients). A DULK-score>3 was good criteria for early diagnosis of AL
      with a sensitivity of 91.7%, a specificity of 55.7%, a positive predictive value
      of 22%, a negative predictive value of 98%, and an area under the ROC curve of
      0.83. If used routinely, the DULK-score would allow diagnosis of AL 3.5 days
      earlier than clinical judgment alone. The DULK-score was superior to common
      diagnostic criteria described in the literature such as the C-reactive protein or
      procalcitonin, in terms of both sensitivity and specificity. CONCLUSION: The DULK
      score is, at present, the most reliable instrument for early diagnosis of AL
      after colorectal surgery and should be integrated into risk management health
      policies aiming to improve the quality of care according to the "failure to
      rescue" concept.

PMID- 25577713
TI  - Noninvasive sphenopalatine ganglion block for acute headache in the emergency
      department: a randomized placebo-controlled trial.
AB  - STUDY OBJECTIVE: We seek to test the efficacy of noninvasive sphenopalatine
      ganglion block for the treatment of acute anterior headache in the emergency
      department (ED) using a novel noninvasive delivery device. METHODS: We conducted
      a randomized, double-blind, placebo-controlled trial evaluating bupivacaine
      anesthesia of the sphenopalatine ganglion for acute anterior or global-based
      headache. This study was completed in 2 large academic EDs. Bupivacaine or normal
      saline solution was delivered intranasally (0.3 mL per side) with the Tx360
      device. Pain and nausea were measured at 0, 5, and 15 minutes by a 100-mm visual
      analog scale. The primary endpoint was a 50% reduction in pain at 15 minutes.
      Telephone follow-up assessed 24-hour pain and nausea through a 0- to 10-point
      verbal scale and adverse effects. RESULTS: The median reported baseline pain in
      the bupivacaine group was 80 mm (IQR 66 mm - 93 mm) and 78.5 mm (IQR 64 mm to
      91.75 mm) in the normal saline solution group. A 50% reduction in pain was
      achieved in 48.8% of the bupivacaine group (20/41 patients) versus 41.3% in the
      normal saline solution group (19/46 patients), for an absolute risk difference of
      7.5% (95% confidence interval [CI] -13% to 27.1%). As a secondary outcome, at 24
      hours, more patients in the bupivacaine group were headache free (24.7%
      difference; 95% CI 2.6% to 43.6%) and more were nausea free (16.9% difference;
      95% CI 0.8% to 32.5%). CONCLUSION: For patients with acute anterior headache,
      sphenopalatine ganglion block with the Tx360 device with bupivacaine did not
      result in a significant increase in the proportion of patients achieving a
      greater than or equal to 50% reduction in headache severity at 15 minutes
      compared with saline solution applied in the same manner.

PMID- 25577714
TI  - Ultrastructure of sperm of the Spotted scat (Scatophagus argus, Linnaeus, 1766)
      observed by scanning and transmission electron microscopy.
AB  - An investigation was conducted to understand the sperm cell morphology and
      ultrastructure of Spotted scat (Scatophagus argus) through scanning and
      transmission electron microscopy. The present study reveals that the sperm of S.
      argus can be differentiated into three major parts - an acrosome-less spherical
      head, a short mid-piece, and a cylindrical flagellum. The scat sperm cell had a
      mean total length of 21.32 +/- 1.80 MUm with the presence of ovoid electron-dense
      nucleus. The mean length and width of ovoid nucleus measured 1.44 +/- 0.34 and
      1.54 +/- 0.33 MUm, respectively. The structural characteristics of the nucleus
      were found to be a shallow axial nuclear fossa and centriolar complex. The two
      centrioles were positioned nearly perpendicular to each other with a conventional
      "9 + 0" pattern in the proximal centriole. The short mid-piece was located
      laterally to the nucleus and contains 5 or 6 spherical and unequal-sized
      mitochondria. The mitochondria were separated from the axoneme by a cytoplasmic
      canal. The flagellum was inserted at the base of the nucleus with the presence of
      an axoneme structure of 9 + 2 paired micro tubules. The sperm flagellum had short
      irregular lateral fins. The present study reveals that Spotted scat sperm can be
      categorized as being of a "primitive or ect-aquasperm type" and belongs to the
      teleostean "type I" sperm. This is the first report on the morphology and
      ultrastructure of sperm in Scatophagidae family.

PMID- 25577715
TI  - Metabolomics for laboratory diagnostics.
AB  - Metabolomics is an emerging approach in a systems biology field. Due to
      continuous development in advanced analytical techniques and in bioinformatics,
      metabolomics has been extensively applied as a novel, holistic diagnostic tool in
      clinical and biomedical studies. Metabolome's measurement, as a chemical
      reflection of a current phenotype of a particular biological system, is nowadays
      frequently implemented to understand pathophysiological processes involved in
      disease progression as well as to search for new diagnostic or prognostic
      biomarkers of various organism's disorders. In this review, we discussed the
      research strategies and analytical platforms commonly applied in the metabolomics
      studies. The applications of the metabolomics in laboratory diagnostics in the
      last 5 years were also reviewed according to the type of biological sample used
      in the metabolome's analysis. We also discussed some limitations and further
      improvements which should be considered taking in mind potential applications of
      metabolomic research and practice. 

PMID- 25577716
TI  - On Epidemiology: Extrapolations, Foibles, and Fictions.

PMID- 25577717
TI  - The role of miRNAs in prostate cancer.

PMID- 25577719
TI  - A causal involvement of the left supramarginal gyrus during the retention of
      musical pitches.
AB  - Brain stimulation studies have previously demonstrated a causal link between
      general pitch memory processes and activity within the left supramarginal gyrus
      (SMG). Building on this evidence, the present study tested the impact of left SMG
      stimulation on two distinct pitch memory phases, retention and encoding.
      Repetitive transcranial magnetic stimulation (rTMS) was employed during the
      retention stage (Experiment 1) and the encoding phase (Experiment 2) of a pitch
      recognition task. Stimulation was applied on a trial-by-trial basis over the left
      SMG (target site) or the vertex (control site). A block without TMS was also
      completed. In Experiment 1, rTMS over the left SMG during pitch retention led to
      significantly increased reaction times compared to control conditions. In
      Experiment 2 no rTMS modulation effects were found during encoding. Experiment 3
      was conducted as a control for non-specific stimulation effects; no effects were
      found when rTMS was applied over the left SMG at the two different time points
      during a perceptual task. Taken together, these findings highlight a phase
      specific involvement of the left SMG in the retention phase of pitch memory,
      thereby indicating that the left SMG is involved in the maintenance of pitch
      information. 

PMID- 25577718
TI  - Depth of remission is a prognostic factor for survival in patients with
      metastatic renal cell carcinoma.
AB  - BACKGROUND: Response remains an important endpoint in clinical cancer trials.
      However, the prognostic utility of best tumor response in metastatic renal cell
      carcinoma (mRCC) remains vague. OBJECTIVE: To define the prognostic relevance of
      the depth of remission in mRCC. DESIGN, SETTING, AND PARTICIPANTS: Pooled data
      from the Pfizer database for 2749 patients from phase 2 and 3 clinical trials in
      mRCC were analyzed. Tumor shrinkage was categorized according to the best
      percentage change in the sum of the largest diameter of target lesions. Outcome
      was computed using Kaplan-Meier curves and correlation was assessed via Cox
      regression, including a 6-mo landmark. INTERVENTION: Sunitinib, sorafenib,
      axitinib, temsirolimus, or temsirolimus and interferon-alpha. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Categorized tumor shrinkage, overall
      survival (OS), progression free survival (PFS). RESULTS AND LIMITATIONS: Major
      tumor shrinkage of 60% or more occurred in approximately 10% of patients and was
      associated with median OS of 54.5 mo. OS expectations steadily decreased with
      depth of remission (26.4, 16.6, 10.4, and 7.3 mo). The association was maintained
      when stratified by type of therapy, line of therapy, and performance status. Cox
      proportional regression analyses for the 6-mo landmark confirmed the prognostic
      relevance of major tumor shrinkage (hazard ratio 0.29, 95% confidence interval
      0.22-0.39; p<0.001). The major limitation of our study is the variability of
      imaging intervals among studies. CONCLUSIONS: This is the first and largest
      analysis of best tumor response in mRCC. We demonstrate that depth of remission
      is an independent prognostic factor in mRCC. PATIENT SUMMARY: It remains unknown
      whether tumor shrinkage during therapy is needed to achieve clinical activity in
      metastatic renal cell carcinoma. Our analysis shows that the magnitude of tumor
      shrinkage correlates with better survival in patients. This observation may be
      used as a clinical research tool in future trials. TRIAL REGISTRATION:
      NCT00054886, NCT00077974, NCT00267748, NCT00338884, NCT00137423, NCT00083889,
      NCT00065468, NCT00678392.

PMID- 25577720
TI  - Student athletes, sudden cardiac death, and lifesaving legislation: a review of
      the literature.
AB  - PURPOSE: The purpose of this article is to present findings of a literature
      review examining the use of automatic external defibrillators (AEDs) for student
      athletes experiencing sudden cardiac arrest and variances in state legislation
      regarding the mandatory placement of AEDs in school gymnasiums and athletic
      fields. METHODS: A broad search of computerized databases was conducted utilizing
      PubMed, Medline, CINHAHL, and the Cochrane Databases, which provided a broad but
      not exhaustive review of the current literature related to student athletes,
      sudden cardiac death, and the use of AEDs. The articles were evaluated and graded
      using Stetler's strength of evidence guidelines. FINDINGS: A total of 17 articles
      are included in this literature review (Stetler's Grade I, n = 1; Grade II, n =
      2; Grade III, n =2; Grade IV, n = 5; Grade V, n = 3; and Grade VI, n = 4). The
      literature produced few meta-analyses of controlled studies, experimental
      studies, and quasi-experimental studies on the topic of student athletes at risk
      for sudden cardiac death. The majority of the literature is based on expert
      opinion, case reports, and retrospective data sets. The literature does support
      the correlation of early cardiopulmonary resuscitation and defibrillation with
      increased survival rates among persons experiencing sudden cardiac arrest.
      CONCLUSIONS: Additional evidence-based research is needed to support the long
      term outcomes of AED legislation and its utility in sparing the lives of student
      athletes. However, the evidence supporting early intervention, a coordinated
      emergency plan, and rapid emergency medical services response is conclusive
      enough to warrant state or federal legislation mandating that AEDs be present in
      all school gyms and athletic fields.

PMID- 25577721
TI  - Beyond DSM-5: an alternative approach to assessing Social Anxiety Disorder.
AB  - This article focuses on the Diagnostic and Statistical Manual of Mental Disorders
      (DSM) classification of Social Anxiety Disorder (SAD). The article details the
      diagnostic criteria for SAD that have evolved in the various editions and
      demonstrates that whilst there have been some positive steps taken to more
      comprehensively define the disorder, further revision is necessary. It will be
      argued that the DSM-5 (APA, 2013) has made some changes to the diagnostic
      criteria of SAD that do not seem to be completely in line with theory and
      research and do not describe SAD effectively in terms of both diversity and
      presentation. This article concludes with the presentation of a proposed set of
      diagnostic criteria that address the concerns raised in the article. The proposed
      criteria reflect a hybrid categorical-dimensional system of classification. 

PMID- 25577722
TI  - Regarding Cuellar-Barboza AB, et al. Change in consumption patterns for treatment
      seeking patients with alcohol use disorder post-bariatric surgery. J Psychosom
      Res 2014; 10.1016/j.jpsychores.2014.06.019. [Epub ahead of print].

PMID- 25577724
TI  - The efficacy of motivational interviewing for disordered gambling: systematic
      review and meta-analysis.
AB  - Motivational interviewing is a client-centered therapeutic intervention that aims
      to resolve ambivalence toward change. We conducted a systematic review and meta
      analysis on the efficacy of motivational interviewing, compared to non
      motivational interviewing controls, in the treatment of disordered gambling.
      Electronic databases were searched for randomized controlled trials that
      evaluated change in gambling behavior using motivational interviewing in adult
      disordered gamblers. The primary outcomes were the weighted mean difference (WMD)
      for change in average days gambled per month and average dollars lost per month.
      The search strategy yielded 447 articles, of which 20 met criteria for full text
      review. Overall, 8 studies (N=730) fulfilled the inclusion criteria for
      systematic review and 5 (N=477) were included in the meta-analysis. Motivational
      interviewing was associated with significant reduction in gambling frequency up
      to a year after treatment delivery. For gambling expenditure, motivational
      interviewing yielded significant reductions in dollars spent gambling compared to
      non-motivational controls at post-treatment only (1-3 months). Overall, the
      results of this review suggest that motivational interviewing is an efficacious
      style of therapy for disordered gambling in the short term. Whether treatment
      effects are maintained over time remains unclear. 

PMID- 25577726
TI  - Primary Total Knee Arthroplasty in Super-obese Patients: Dramatically Higher
      Postoperative Complication Rates Even Compared to Revision Surgery.
AB  - This study utilized a national database to evaluate 90 day postoperative
      complication rates after total knee arthroplasty (TKA) in super obese (BMI > 50
      kg/m(2)) patients (n = 7666) compared to non-obese patients (n = 1,212,793),
      obese patients (n = 291,914), morbidly obese patients (n = 169,308) and revision
      TKA patients (n = 28,812). Super obese patients had significantly higher rates of
      local and systemic complications compared to all other BMI groups as well as
      those undergoing revision TKA with higher rates of venous thromboembolism (VTE),
      infection, and medical complications. Super obesity is associated with
      dramatically increased rates of postoperative complications after TKA compared to
      non-obese, obese, and morbidly obese patients as well as those undergoing
      revision TKA.

PMID- 25577725
TI  - Information processing speed as a predictor of IQ in children with and without
      specific language impairment in grades 3 and 8.
AB  - PURPOSE: This study investigated (1) whether nonlinguistic processing speed
      predicts nonverbal IQ in TD children and children with SLI and (2) if the
      proposed relationship is different at two time points. METHOD: The participants
      consisted of a subset of a longitudinal dataset, 55 typically developing children
      and 55 children with SLI. Children completed four nonverbal speed tasks and four
      subtests of the WISC-III. The WISC-III subtests requiring timed and untimed
      responses were examined separately. RESULTS: Linear mixed model analyses
      indicated that in both groups, processing speed predicted nonverbal IQ subtests
      that reward speedy responses, but not IQ subtests that do not. The relationships
      between processing speed and IQ with speed bonuses did not differ at grades 3 and
      8, and these relationships also were not significantly different in children with
      SLI and their TD peers. CONCLUSIONS: The results suggest that the presence of
      processing speed limitations in many children with SLI raises questions about the
      utility of timed nonverbal IQ measures as tools for diagnosis of SLI. Future
      studies should investigate other cognitive assessments that could be used as
      inclusionary criteria for SLI. LEARNING OUTCOMES: The reader will be able to (1)
      describe the relationship between processing speed and nonverbal IQ in children
      with TD and SLI and (2) discuss problems using an IQ criterion to diagnose
      children as having SLI.

PMID- 25577723
TI  - Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor
      Evaluated by IntraVascular UltraSound (PRECISE-IVUS Trial): Study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Although the positive association between achieved low-density
      lipoprotein cholesterol (LDL-C) level and the risk of coronary artery disease
      (CAD) has been confirmed by randomized studies with statins, many patients remain
      at high residual risk of events suggesting the necessity of novel pharmacologic
      strategies. The combination of ezetimibe/statin produces greater reductions in
      LDL-C compared to statin monotherapy. PURPOSE: The Plaque REgression with
      Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by
      IntraVascular UltraSound (PRECISE-IVUS) trial was aimed at evaluating the effects
      of ezetimibe addition to atorvastatin, compared with atorvastatin monotherapy, on
      coronary plaque regression and change in lipid profile in patients with CAD.
      METHODS: The study is a prospective, randomized, controlled, multicenter study.
      The eligible patients undergoing IVUS-guided percutaneous coronary intervention
      will be randomly assigned to receive either atorvastatin alone or atorvastatin
      plus ezetimibe (10 mg) daily using a web-based randomization software. The dosage
      of atorvastatin will be increased by titration within the usual dose range with a
      treatment goal of lowering LDL-C below 70 mg/dL based on consecutive measures of
      LDL-C at follow-up visits. IVUS will be performed at baseline and 9-12 months
      follow-up time point at participating cardiovascular centers. The primary
      endpoint will be the nominal change in percent coronary atheroma volume measured
      by volumetric IVUS analysis. CONCLUSION: PRECISE-IVUS will assess whether the
      efficacy of combination of ezetimibe/atorvastatin is noninferior to atorvastatin
      monotherapy for coronary plaque reduction, and will translate into increased
      clinical benefit of dual lipid-lowering strategy in a Japanese population.

PMID- 25577727
TI  - Inhibition of lipopolysaccharide-induced liver injury in rats treated with a
      hepatic drug-metabolizing enzyme inducer p,p'-DDT.
AB  - Hepatocellular hypertrophy in association with drug-metabolizing enzyme induction
      is considered to be an adaptive change associated with drug metabolism. To
      improve our understanding of liver hypertrophy, we determined the effect of a
      single ip injection of either lipopolysaccharide (LPS) or vehicle in male F344
      rats with hepatocellular hypertrophy induced by oral delivery of p,p'-DDT for 2
      weeks. The rats were sacrificed 3h or 24h after LPS or vehicle injection. LPS
      induced a focal hepatocellular necrosis in rats fed the control diet. When rats
      pre-treated with p,p'-DDT were injected with LPS, necrotic foci surrounded by
      ballooned hepatocytes were observed in the liver. The change was consistent with
      reduced LPS-mediated increases in plasma hepatic biomarkers, neutrophil influx,
      and apoptosis, and also associated with hepatic mRNA levels of TNF-alpha, CYPs,
      and NOS2. By contrast, when combined with p,p'-DDT and LPS, faint hepatocellular
      fatty change was extended, together with a synergistic increase in total blood
      cholesterol. These results suggest that hepatocytes exposed to p,p'-DDT are
      protected from the cell-lethal toxic effects of an exogenous stimulus, resulting
      in cell ballooning rather than necrosis in association with reduced inflammation
      and apoptosis, but compromised by an adverse effect on lipid metabolism. 

PMID- 25577728
TI  - Improving the quality of plastic surgery systematic reviews.

PMID- 25577729
TI  - Evaluating the performance of the Framingham Diabetes Risk Scoring Model in
      Canadian electronic medical records.
AB  - OBJECTIVE: The objective of this study was to evaluate the performance of the
      Framingham Diabetes Risk Scoring Model (FDRSM) in a Canadian population, using
      the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) database.
      METHODS: We analyzed the records of 571 631 patients, between the ages of 45 and
      64, between 2002 and 2005, by extracting the most recent laboratory and
      examination results, including age, sex, body mass index, fasting blood glucose,
      high-density lipoprotein, triglycerides and blood pressure. We calculated the
      risk scores of these patients based on the FDRSM. We tracked these patients for 8
      years to find out whether or not they were diagnosed with diabetes. We used the
      area under the receiver operating characteristics curve (AROC) to estimate the
      discrimination capability of the FDRSM on our study sample and compared it with
      the AROC reported in the original Framingham diabetes study. RESULTS: The AROC
      for our main research sample of 1970 patients for whom all risk factors and
      follow-up data were available was 78.6% compared to the AROC of 85% reported in
      the FDRSM. We found that 70.1% of our main sample had risks lower than 3%; 16.3%
      had risks between 3% and 10%; and 13.6% had risks greater than 10% for diabetes
      over the following 8-year period. CONCLUSIONS: The discrimination capability of
      the FDRSM Canadian electronic medical records is fair. However, building a more
      accurate model for predicting diabetes based on the characteristics of Canadian
      patients is highly recommended.

PMID- 25577730
TI  - Biomechanical comparison of graft fixation at 30 degrees  and 90 degrees  of
      elbow flexion for ulnar collateral ligament reconstruction by the docking
      technique.
AB  - BACKGROUND: Ulnar collateral ligament (UCL) injuries have been successfully
      treated by the docking reconstruction. Although fixation of the graft has been
      suggested at 30 degrees  of elbow flexion, no quantitative biomechanical data
      exist to provide guidelines for the optimal elbow flexion angle for graft
      fixation. METHODS: Testing was conducted on 10 matched pairs of cadaver elbows
      with use of a loading system and optoelectric tracking device. After
      biomechanical data on the native UCL were obtained, reconstruction by the docking
      technique was performed with use of palmaris longus autograft with one elbow
      fixated at 30 degrees  and the contralateral elbow at 90 degrees  of elbow
      flexion. Biomechanical testing was undertaken on these specimens. RESULTS: The
      load to failure of the native UCL (mean, 20.1 N-m) was significantly higher (P =
      .004) than that of the reconstructed UCL (mean, 4.6 N-m). There was no
      statistically significant difference in load to failure of the UCL
      reconstructions fixated at 30 degrees  of elbow flexion (average, 4.86 N-m)
      compared with those at 90 degrees  (average, 4.35 N-m). Elbows reconstructed at
      30 degrees  and 90 degrees  of elbow flexion produced similar kinematic coupling
      and valgus laxity characteristics compared with each other and with the intact
      UCL. Although not statistically significant, the reconstructions fixated at 30
      degrees  more closely resembled the biomechanical characteristics of the intact
      elbow than did reconstructions fixated at 90 degrees . CONCLUSION: No
      statistically significant difference was found in comparing the docking technique
      of UCL reconstruction with graft fixation at 30 degrees  vs. 90 degrees  of elbow
      flexion.

PMID- 25577731
TI  - Symbolic online exposure for spider fear: habituation of fear, disgust and
      physiological arousal and predictors of symptom improvement.
AB  - BACKGROUND AND OBJECTIVES: This research compared the effects of real versus
      hyper-real images on anxiety, disgust, and physiological arousal during internet
      delivered exposure in high spider-fearfuls. Hyper-real images were digitally
      altered to highlight fearful aspects. A further aim was to examine self-reported
      and behavioural therapeutic outcomes and exposure-related predictors of these
      outcomes. METHODS: Twenty-eight females were randomised to real (n = 14) or hyper
      real (n = 14) treatment groups and nine participants were subsequently allocated
      to a wait-list control group. Treatment groups viewed an 8-stage exposure
      hierarchy of real or hyper-real spider images. Subjective anxiety and disgust
      ratings were taken during each stage (0, 60, 120, 180 s) with heart rate and skin
      conductance recorded throughout. RESULTS: Anxiety, disgust and physiological
      arousal habituated within each exposure stage, with no differential effect of
      real compared to hyper-real images. Both treatment groups but not controls
      demonstrated significant reductions in behavioural avoidance and self-reported
      phobic symptoms from pre-treatment to post-treatment with large effect sizes
      noted. The change in within-stage habituation of anxiety, disgust and heart rate,
      between the first and last stage, predicted improvement in behavioural avoidance
      at post-treatment. This suggests that generalisation of habituation to multiple
      images is an important predictor of improvement. LIMITATIONS: While findings in
      relation to therapeutic outcome should be considered preliminary, clear
      relationships were found between exposure-related variables and outcome among
      those who undertook treatment. CONCLUSIONS: Findings provide evidence in support
      of the efficacy of online image-based exposure and have implications for
      informing further research into the underlying mechanisms of image-based exposure
      treatment.

PMID- 25577733
TI  - Line differences in Cor/Lea and fructan biosynthesis-related gene transcript
      accumulation are related to distinct freezing tolerance levels in synthetic wheat
      hexaploids.
AB  - In common wheat, cultivar differences in freezing tolerance are considered to be
      mainly due to allelic differences at two major loci controlling freezing
      tolerance. One of the two loci, Fr-2, is coincident with a cluster of genes
      encoding C-repeat binding factors (CBFs), which induce downstream Cor/Lea genes
      during cold acclimation. Here, we conducted microarray analysis to study
      comprehensive changes in gene expression profile under long-term low-temperature
      (LT) treatment and to identify other LT-responsive genes related to cold
      acclimation in leaves of seedlings and crown tissues of a synthetic hexaploid
      wheat line. The microarray analysis revealed marked up-regulation of a number of
      Cor/Lea genes and fructan biosynthesis-related genes under the long-term LT
      treatment. For validation of the microarray data, we selected four synthetic
      wheat lines that contain the A and B genomes from the tetraploid wheat cultivar
      Langdon and the diverse D genomes originating from different Aegilops tauschii
      accessions with distinct levels of freezing tolerance after cold acclimation.
      Quantitative RT-PCR showed increased transcript levels of the Cor/Lea, CBF, and
      fructan biosynthesis-related genes in more freezing-tolerant lines than in
      sensitive lines. After a 14-day LT treatment, a significant difference in fructan
      accumulation was observed among the four lines. Therefore, the fructan
      biosynthetic pathway is associated with cold acclimation in development of wheat
      freezing tolerance and is another pathway related to diversity in freezing
      tolerance, in addition to the CBF-mediated Cor/Lea expression pathway. 

PMID- 25577732
TI  - Evidence for alternative splicing mechanisms in meadow fescue (Festuca pratensis)
      and perennial ryegrass (Lolium perenne) Rubisco activase gene.
AB  - Rubisco activase is required to regulate the catalytic activity of Rubisco in
      plants, in an ATP-dependent manner. One or two Rubisco activase proteins have
      been identified in different plant species. In some species, the two isoforms are
      the products of alternative splicing of the Rubisco activase gene. The aim of
      this study was to confirm that Lolium perenne and Festuca pratensis plants have
      two isoforms of Rubisco activase and that they are the products of alternative
      splicing of common pre-mRNA. Protein gel blot analyses indicated that L. perenne
      and F. pratensis leaves contained two Rubisco activase proteins. Sequence
      analysis of cDNA and genomic DNA showed that differential splicing generated two
      mRNAs that differed in sequence only in the inclusion of 48 bp. The insertion
      contains a stop codon leading to the synthesis of a shorter polypeptide. Under
      the conditions of our experiment, the shorter splicing variant of L. perenne and
      F. pratensis Rubisco activase gene was preferentially produced. Any further
      studies concerning Rubisco activase genes in L. perenne and/or F. pratensis
      plants should take into consideration the mechanism of its expression.

PMID- 25577734
TI  - Wounding induces changes in tuber polyamine content, polyamine metabolic gene
      expression, and enzyme activity during closing layer formation and initiation of
      wound periderm formation.
AB  - Tuber wound-healing processes are complex, and the associated regulation and
      modulation of these processes are poorly understood. Polyamines (PA) are involved
      in modulating a variety of responses to biotic and abiotic plant stresses and
      have been suggested to be involved in tuber wound responses. However, the time
      course of wound-induced changes in tuber PA content, activity of key biosynthetic
      enzymes and associated gene expression has not been determined and coordinated
      with major wound-healing processes. The objective of this study was to determine
      these wound-induced changes and their coordination with wound-healing processes.
      Wounding induced increases in putrescine (Put) and spermidine (Spd), but had only
      minor effects on spermine (Spm) content during the 168 h time course which
      encompassed the initiation and completion of the closing layer formation, and the
      initiation of cell division and wound periderm formation. As determinants of the
      first committed step in PA biosynthesis, arginine and ornithine decarboxylase
      (ADC and ODC, respectively) activities were below levels of detectability in
      resting tubers and expression of genes encoding these two enzymes was low. Within
      6h of wounding, increases in the in vitro activities of ADC and ODC and
      expression of their cognate genes were observed. Expression of a gene encoding S
      adenosylmethionine decarboxylase, required for Spd and Spm biosynthesis, was also
      increased 6h after wounding and remained elevated throughout the time course.
      Expression of a polyamine catabolic gene, encoding polyamine oxidase, was down
      regulated after wounding. Results indicated a rapid wound-induced increase in PA
      biosynthesis during closing layer formation and the time of nuclei entry and exit
      from S-phase. PA content remained elevated as wound-induced cells became
      meristematic and initiated formation of the wound periderm suggesting sustained
      involvement in wound-healing.

PMID- 25577736
TI  - Seasonal variability and inter-species comparison of metal bioaccumulation in
      caged gammarids under urban diffuse contamination gradient: implications for
      biomonitoring investigations.
AB  - Although caging of Gammarus species offers promising lines of inquiry to monitor
      metal bioavailability in freshwaters, the interspecies responsiveness to metal
      exposures is still unclear. In addition, abiotic factors inherent to
      transplantation can hamper the interpretation of field bioaccumulation data. To
      assess the relevance of using gammarids as biomonitors, we investigated the
      seasonal influence on metal bioaccumulation in two common species, Gammarus pulex
      and Gammarus fossarum. During four seasons, caged gammarids were deployed on
      three sites along the Seine River exhibiting a diffuse gradient of multi-metal
      contamination: a site upstream and two sites downstream from the Paris megacity.
      For each seasonal deployment, metal concentrations in animals were determined
      after 7d-exposure in situ (Ag, Cd, Co, Cu, Mn, Ni, Pb and Zn). Results show that
      the seasonal patterns of metal contaminations are similar between both Gammarus
      species, and closely related to the river axis' contamination gradient.
      Statistical analyses indicate that bioaccumulation of essential metals in both
      species is influenced by season, especially by water temperature. This highlights
      the necessity to consider this climatic factor inherent to the deployment period
      for a reliable interpretation of bioaccumulation data in the field. The
      comparison of accumulation factors suggests that these two species coming from
      different geochemical origins display similar abilities to internalize metals.
      This generic responsiveness of caged gammarids supports their use as sentinel
      organisms to quantify low spatiotemporal variations in metal bioavailabilities. 

PMID- 25577735
TI  - Efficacy of sunitinib in patients with metastatic or unresectable renal cell
      carcinoma and renal insufficiency.
AB  - AIM: The aim of this retrospective, registry-based study was to analyse treatment
      outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with
      sunitinib and renal insufficiency (RI). METHODS: The cohort included 790 patients
      treated with sunitinib between 2006 and 2013. At the start of sunitinib therapy
      22, 234, and 534 patients had severe (glomerular filtration rate [GFR]
      <30ml/min/1.73m(2)), moderate (GFR 30-60 ml/min/1.73m(2)) or mild RI/normal renal
      function (GFR >60ml/min/1.73m(2)), respectively. RESULTS: For the three groups
      defined above, median progression-free survival (PFS) (95% confidence interval
      [CI]) was 5.3 months (0.1-18.5), 8.1 months (6.2-9.9) and 11.3 months (9.4-13.2)
      (p=0.244), and median overall survival (OS) was 26.3 months (1.2-51.4), 21.2
      months (13.2-29.1) and 26.3 months (22.6-29.9) (p=0.443), respectively. The
      disease control rates were 45.5%, 56.4% and 59.2%, respectively (p=0.374). No
      unexpected toxicity was reported in the patients with RI, but the treatment was
      more frequently discontinued because of adverse events and the duration of
      therapy was significantly shorter in these patients (p=0.007). CONCLUSIONS:
      Duration of first-line targeted treatment for mRCC was significantly shorter for
      patients with RI, and may have translated into a trend to shorter PFS. These
      results highlight the need for optimal management of side-effects in patients
      with mRCC and RI.

PMID- 25577737
TI  - Transport of graphene oxide in saturated porous media: effect of cation
      composition in mixed Na-Ca electrolyte systems.
AB  - The influence of cation composition in mixed Na-Ca electrolyte systems on the
      transport of graphene oxide particles in saturated porous media was studied.
      Column experiments were conducted to elucidate the transport behavior of GO by
      varied molar ratios of Ca2+/Na+ but of constant ionic strength (IS). The results
      show that retention of GO in sand column is strongly dependent on IS in the
      presence of Ca2+, featuring serious deposition rates (Rd) at the higher IS of 10
      mM. The maximum Rd was 48.22% at 1 mM and 98.53% at 10 mM. However, there was no
      obvious difference in GO retention in solutions that only contained Na+ when the
      IS increased from 1 to 10 mM, and the Rd was 35.17% and 38.21% respectively. The
      molar ratio of Ca2+/Na+ in solution was much more influential in altering the
      particle retention behavior at the higher IS of 10 mM, compared with little
      influence at 1 mM. It was supposed that compression of diffuse double layers
      mainly controlled GO deposition under lower IS, while charge neutrality and metal
      (Ca2+) bridging played a significant role at the higher IS. A numerical advection
      dispersion-retention model considering the combined processes of Langmuirian
      dynamics blocking and depth-dependent straining was successfully developed to
      simulate the transport process of GO through the sand column. Derjaguin-Landau
      Verwey-Overbeek (DLVO) interaction energy calculations were also performed to
      better understand the mechanisms of GO mobility. Coupling analysis of
      breakthrough experiments, DLVO theory and numerical modeling in this work
      provides insight into the mechanisms of GO transport in saturated porous media
      and is useful for reliable prediction of nanoparticle penetration through the
      vadose zone.

PMID- 25577738
TI  - Spotlight on fish: light pollution affects circadian rhythms of European perch
      but does not cause stress.
AB  - Flora and fauna evolved under natural day and night cycles. However, natural
      light is now enhanced by artificial light at night, particularly in urban areas.
      This alteration of natural light environments during the night is hypothesised to
      alter biological rhythms in fish, by effecting night-time production of the
      hormone melatonin. Artificial light at night is also expected to increase the
      stress level of fish, resulting in higher cortisol production. In laboratory
      experiments, European perch (Perca fluviatilis) were exposed to four different
      light intensities during the night, 0 lx (control), 1 lx (potential light level
      in urban waters), 10 lx (typical street lighting at night) and 100 lx. Melatonin
      and cortisol concentrations were measured from water samples every 3h during a 24
      hour period. This study revealed that the nocturnal increase in melatonin
      production was inhibited even at the lowest light level of 1 lx. However,
      cortisol levels did not differ between control and treatment illumination levels.
      We conclude that artificial light at night at very low intensities may disturb
      biological rhythms in fish since nocturnal light levels around 1 lx are already
      found in urban waters. However, enhanced stress induction could not be
      demonstrated.

PMID- 25577739
TI  - Prevalence of toxin-producing Clostridium botulinum associated with the macroalga
      Cladophora in three Great Lakes: growth and management.
AB  - The reemergence of avian botulism caused by Clostridium botulinum type E has been
      observed across the Great Lakes in recent years. Evidence suggests an association
      between the nuisance algae, Cladophora spp., and C. botulinum in nearshore areas
      of the Great Lakes. However, the nature of the association between Cladophora and
      C. botulinum is not fully understood due, in part, to the complex food web
      interactions in this disease etiology. In this study, we extensively evaluated
      their association by quantitatively examining population size and serotypes of C.
      botulinum in algal mats collected from wide geographic areas in lakes Michigan,
      Ontario, and Erie in 2011-2012 and comparing them with frequencies in other
      matrices such as sand and water. A high prevalence (96%) of C. botulinum type E
      was observed in Cladophora mats collected from shorelines of the Great Lakes in
      2012. Among the algae samples containing detectable C. botulinum, the population
      size of C. Botulinum type E was 10(0)-10(4) MPN/g dried algae, which was much
      greater (up to 10(3) fold) than that found in sand or the water column,
      indicating that Cladophora mats are sources of this pathogen. Mouse
      toxinantitoxin bioassays confirmed that the putative C. botulinum belonged to the
      type E serotype. Steam treatment was effective in reducing or eliminating C.
      botulinum type E viable cells in Cladophora mats, thereby breaking the potential
      transmission route of toxin up to the food chain. Consequently, our data suggest
      that steam treatment incorporated with a beach cleaning machine may be an
      effective treatment of Cladophora-borne C. botulinum and may reduce bird
      mortality and human health risks.

PMID- 25577740
TI  - Clinical significance of fecal occult blood screening in patients before
      percutaneous coronary intervention.
AB  - BACKGROUND: The most common reason for premature discontinuation of dual anti
      platelet therapy (DAPT) after coronary stenting is the manifestation of
      gastrointestinal bleeding. Before percutaneous coronary interventions (PCIs), we
      screened patients who tested positive for fecal occult blood (fecOB). METHODS AND
      RESULTS: On 1789 consecutively admitted cardiac catheterization patients, we
      performed fecOB examinations; 647 of these patients received PCIs, and 232 of
      them were fecOB positive. Ultimately, we performed 165 colonoscopies and detected
      3 early cancer lesions. CONCLUSIONS: Positive results on fecOB screening, before
      PCI, could indicate lower intestinal lesions. We can perform surgical cancer
      procedures safely, even with aspirin usage.

PMID- 25577741
TI  - Acute effect of sildenafil on inflammatory markers/mediators in patients with
      vasculogenic erectile dysfunction.
AB  - BACKGROUND: Erectile dysfunction (ED) is associated with an incremental
      inflammatory activation. Evidence suggests that chronic phosphodiesterase 5 (PDE
      5) inhibition may have a favorable effect on inflammatory activation and
      surrogate markers of ED. The aim of this study is to investigate the acute effect
      of sildenafil on circulating pro-inflammatory markers/mediators in ED patients.
      METHODS: The study comprised a randomized, double-blind, crossover trial carried
      out on two separate arms: one with sildenafil 100mg, and one with placebo. Twenty
      seven subjects participated in the study (seven in the pilot and 20 in the main
      phase). In the main phase, blood samples were collected at baseline and at 2 and
      4h after sildenafil or placebo administration to determine fibrinogen, high
      sensitivity C-reactive protein (hsCRP), high sensitivity interleukin-6 (hsIL-6)
      and tumor necrosis factor alpha (TNF-alpha). RESULTS: Administration of
      sildenafil produced a significant sustained reduction of fibrinogen, hsCRP and
      hsIL-6 (maximal absolute response of -44mg/dl, 0.42mg/l and 0.68pg/ml at 4h).
      Likewise, TNF-alpha was acutely decreased after sildenafil (maximal response of 
      13pg/ml, 2h). The effect of sildenafil on fibrinogen, hsCRP and hsIL-6 and TNF
      alpha was independent of the baseline values of these markers/mediators or the
      baseline testosterone level (all P<0.05). Soluble vascular cell adhesion molecule
      1 (sVCAM-1) levels remained unchanged. CONCLUSIONS: The present study shows for
      the first time the acute effect of sildenafil administration on pro-inflammatory
      markers/mediators in men with vasculogenic ED. This finding may have important
      implications in ED patients who are considered to be at increased cardiovascular
      risk.

PMID- 25577742
TI  - Traumatic tricuspid regurgitation with ruptured chordae tendinae caused by a
      punch in the chest.

PMID- 25577743
TI  - How baroreceptor dysfunction could predispose to the takotsubo syndrome.

PMID- 25577744
TI  - Is early sudden death in the course of arrhythmogenic cardiomyopathy due to
      initial Brugada syndrome?

PMID- 25577745
TI  - Impact of platelet-derived growth factor-BB on ischemic myocardial injury after
      thrombus aspiration for ST-segment elevation myocardial infarction.

PMID- 25577746
TI  - Heavily calcified plaques in acutely angulated coronary segment: high risk
      features of rotablation resulting in Rotawire transection and coronary
      perforation.

PMID- 25577748
TI  - Clinical characteristics, myocardial perfusion deficits, and clinical outcomes of
      patients with non-specific chest pain hospitalized for suspected acute coronary
      syndrome: a 4-year prospective cohort study.
AB  - BACKGROUND: Although the prognostic role of stress SPECT MPI is generally well
      established, its value in predicting non-fatal cardiac events in patients with
      acute, non-specific chest pain (NSCP) remains unclear. The aims of this study are
      1) to describe the baseline clinical characteristics and prevalence of myocardial
      perfusion (MP) deficits, by use of an adenosine stress SPECT MPI, in NSCP
      patients without known CAD discharged after hospitalization for suspected ACS;
      and 2) to prospectively describe the 4-year clinical outcome in terms of all
      cause and cardiac mortality; hospitalization and coronary revascularization
      procedures; and cardio-vascular events in patients with and without MP deficits.
      METHODS AND RESULTS: We evaluated a series of 272 consecutive patients with acute
      NSCP and aged 18-75years. ICD10-based registries were used to determine the
      primary outcome (a composite measure of incident CAD death, ACS, or
      revascularization) and two secondary outcomes (1. all-cause death; 2. a composite
      measure of cardiovascular death, ACS, revascularization, or stroke). Forty two
      (15%) participants had a MP deficit. During follow-up (median 1361days), 7
      participants had a primary event, 4 died, and 20 had a secondary composite event.
      Annual event rates were 0.70, 0.39 and 2.07, respectively. MP deficits predicted
      both subsequent primary and composite secondary events (HR: 7.54; 95% CI=[1.69;
      33.69] and 2.93 (95% CI=[1.10; 7.81], respectively). Usual clinical cardiac risk
      classification could not meaningfully differentiate between patients with and
      without MP deficits. CONCLUSION: SPECT MPI substantially improved prediction of
      incident CAD beyond usual clinical procedures and risk classification systems
      among NSCP patients.

PMID- 25577747
TI  - Simple physical performance measures and vascular health in late midlife women:
      the Study of Women's Health across the nation.
AB  - BACKGROUND: Physical performance measures have been shown to predict mortality
      and incident cardiovascular disease (CVD) mainly in elderly populations. We
      evaluated whether physical performance measures are associated with vascular
      health indices (carotid intima-media thickness (cIMT), adventitial diameter (cAD)
      and carotid plaque) in a large sample of multi-ethnic, late midlife women.
      METHODS: Participants from the Study of Women's Health Across the Nation free of
      CVD and who had carotid ultrasound assessed at the 12th annual visit were
      evaluated. Physical function (PF) measures at visit 12 included: average 40-foot
      walking speed and average time needed for sit-to-stand assessment. RESULTS: A
      total of 1103 women (53.7% White, 30.5% Black, 15.9% Chinese) aged 59.6+/
      2.7years at visit 12, were included. In models adjusted for study site, race,
      current age, menopausal status and systolic blood pressure, slower walking speed
      and longer time needed for sit-to-stand were significantly associated with wider
      cAD, thicker cIMT and a higher probability of a high level of carotid plaque
      burden (all P-values<0.05). Associations between walking speed and cAD, and
      between time needed for sit-to-stand and cAD, remained significant (P=0.04) or
      marginally significant (P=0.07), respectively, after additional adjustment for
      CVD risk factors, medications and physical activity. However, the associations
      between PF measures and cIMT and plaque burden were largely explained by
      traditional CVD risk factors. CONCLUSIONS: The current study suggests that worse
      performance in simple objective PF tests may be an early indicator of vascular
      structural changes that precede vascular disease among women at late midlife.

PMID- 25577749
TI  - Isolated cardiac sarcoidosis: clinical characteristics, diagnosis and treatment.
AB  - Sarcoidosis is a systemic disease characterized by the development of
      noncaseating epithelioid granulomas in multiple organs. Despite extensive
      investigations over a long period of time, the etiology of this disease remains
      unknown. Cardiac involvement of this disease is the most ominous complication
      leading to fatal outcome. Recently, attention has been focused on isolated
      cardiac sarcoidosis, which exists without clinically apparent sarcoidosis
      elsewhere. One of the critical issues of isolated cardiac sarcoidosis is
      difficulty in diagnosis, since existence of the cardiac lesion should be detected
      from cardiac manifestations alone. Because specificity of biomarkers or
      sensitivity of histological examination of biopsied sample is very low, diagnosis
      of isolated cardiac sarcoidosis mainly depends on imaging modalities. In this
      review article we summarized current knowledge on the pathogenesis of
      sarcoidosis, clinical features of cardiac sarcoidosis especially that isolated to
      the heart by showing some typical cases. Utilities and problems of diagnostic
      imaging tests for this condition including echocardiography, cardiac magnetic
      resonance imaging, and fluorodeoxyglucose-positron emission tomography are
      discussed. Advances in pharmacological and nonpharmacological treatment for
      cardiac sarcoidosis have improved the prognosis of cardiac sarcoidosis to a great
      deal; however, there are many issues that remain to be solved in the management
      of isolated cardiac sarcoidosis. 

PMID- 25577750
TI  - Low socioeconomic status of a patient's residential area is associated with worse
      prognosis after acute myocardial infarction in Sweden.
AB  - INTRODUCTION: Previous studies have established a relationship between
      socioeconomic status (SES) and survival in coronary heart disease. Acute cardiac
      care in Sweden is considered to be excellent and independent of SES. We studied
      the influence of area-level socioeconomic status on mortality after
      hospitalization for acute myocardial infarction (AMI) between 1995 and 2013 in
      the Gothenburg metropolitan area, which has little over 800,000 inhabitants and
      includes three city hospitals. METHODS: Data were obtained from the SWEDEHEART
      registry (Swedish Websystem for Enhancement of Evidence-Based Care in Heart
      Disease Evaluated According to Recommended Therapies) and the Swedish Central
      Bureau of Statistics for patients hospitalized for ST-elevation myocardial
      infarction (STEMI) and non-STEMI in the city of Gothenburg in Western Sweden. The
      groups were compared using Cox proportional hazards regression and logistic
      regression. RESULTS: 10,895 (36% female) patients were hospitalized due to AMI
      during the study period. Patients residing in areas with lower SES had higher
      rates of smoking and diabetes (P<0.001), and were also at increased risk of
      developing complications, including heart failure and cardiogenic shock (P<0.05).
      Living in an area with lower SES associated with increased risk of dying after an
      AMI also in models adjusted for risk factors (P<0.05). CONCLUSION: Also in a
      country with strong egalitarian traditions, lower SES associates with worse
      prognosis after AMI, an association that persists after adjustments for
      differences in traditional cardiovascular risk factors.

PMID- 25577751
TI  - Aspirin underuse, non-compliance or cessation: definition, extent, impact and
      potential solutions in the primary and secondary prevention of cardiovascular
      disease.
AB  - Despite momentous breakthroughs in unraveling the pathophysiology of many chronic
      conditions and developing novel therapeutic agents, everyday clinical practice is
      still fraught with inadequate or inappropriate use of treatments with proven
      benefits. Aspirin is a paradigmatic example, as it is used for the primary and
      secondary prevention of cardiovascular disease and appears to have a beneficial
      impact on cancer risk. Yet, underuse, non-compliance or cessation of aspirin are
      not uncommon, may have an important clinical impact, and are not aggressively
      prevented or managed. Increasing the awareness of the extent and impact of
      aspirin underuse, non-compliance or cessation, and intensifying efforts at
      preventing them are worthy goals likely to yield significant benefits on
      cardiovascular morbidity and mortality worldwide, and possibly also on cancer
      outcomes. 

PMID- 25577752
TI  - Monitoring of the jugular venous pressure response to diuretics in constrictive
      pericarditis.

PMID- 25577753
TI  - Prevalence and outcome of patients with left bundle branch block and suspected
      acute myocardial infarction.

PMID- 25577754
TI  - Multi-modality imaging aids the diagnosis of bilateral coronary-cameral fistulae
      with involvement of the left ventricle.

PMID- 25577755
TI  - Prognostic value of serum galectin-3 in patients with heart failure: a meta
      analysis.

PMID- 25577756
TI  - High incidence of coronary spasm after percutaneous coronary interventions:
      comparison between new generation drug-eluting stent and bare-metal stent.

PMID- 25577757
TI  - Potentiation of 17beta-estradiol on neuroexcitability by HCN-mediated
      neuromodulation of fast-afterhyperpolarization and late-afterdepolarization in
      low-threshold and sex-specific myelinated Ah-type baroreceptor neurons via GPR30
      in female rats.

PMID- 25577758
TI  - Anomalous origin of Left Coronary Artery from the Pulmonary Artery (ALCAPA): a
      rare presentation in late adulthood.

PMID- 25577759
TI  - Off-pump coronary artery bypass grafting may prevent acute renal failure in
      patients with non-dialysis dependent chronic renal dysfunction: an aggregate meta
      analysis.

PMID- 25577760
TI  - Correlation between peak expiratory flow rate and NT-proBNP in patients with
      acute heart failure. An analysis from ASCEND-HF trial.

PMID- 25577761
TI  - Pericardial bleeding risk with non-vitamin K oral anticoagulants: a meta
      analysis.

PMID- 25577762
TI  - Prediction of absolute risk reduction of cardiovascular events with perindopril
      for individual patients with stable coronary artery disease - results from
      EUROPA.
AB  - BACKGROUND: Angiotensin-converting-enzyme inhibition reduces the risk of
      cardiovascular events at a group level. Presumably, the absolute effect of
      treatment varies between individuals. We sought to develop multivariable
      prediction scores to estimate individual treatment effect of perindopril in
      patients with stable coronary artery disease (sCAD). METHODS: In EUROPA trial
      participants, we estimated the individual patient 5-year absolute risk reduction
      (ARR) of major adverse cardiovascular events(MACE) by perindopril. Predictions
      were based on a new Coxproportional-hazards model with clinical characteristics
      and an external risk score in combination with the observed relative risk
      reduction. Second, a genetic profile modifying the relative efficacy of
      perindopril was added. The individual patient ARR was defined as the difference
      in MACE risk with and without treatment. The group level impact of selectively
      treating patients with the largest predicted treatment effect was evaluated using
      net benefit analysis. RESULTS: The risk score combining clinical and genetic
      characteristics estimated the 5-year absolute treatment effect to be absent or
      adverse in 27% of patients. On the other hand, the risk score estimated a small 5
      year ARR of <=2% (NNT5>=50) in 20% of patients, a modest ARR of 2-4% (NNT5 25-50)
      in 26%, and a large ARR of >=4% (NNT5<=25) in 28%. The external risk score
      yielded similar predictions. Selective prediction-based treatment resulted in
      higher net benefit compared to treat everyone at any treatment threshold.
      CONCLUSION: A prediction score combining clinical characteristics and genetic
      information can quantify the ARR of MACE by perindopril for individual patients
      with sCAD and may be used to guide treatment decisions. TRIAL REGISTRATION
      NUMBER: ISRCTN37166280.

PMID- 25577763
TI  - Differences in maximum phonation time based on body mass index in chronic heart
      failure patients.

PMID- 25577764
TI  - Q waves and failed ST resolution: will intra-myocardial haemorrhage be a concern
      in reperfusing "late presenting" STEMIs?
AB  - Animal studies have demonstrated that intra-myocardial haemorrhage does not occur
      with STEMI unless myocardium is reperfused with blood. Managing late presenting
      STEMI is a challenge because reperfusion of non-viable myocardium will not
      salvage myocardium but potentially causes intra-myocardial haemorrhage which has
      negative connotations. In the infarct leads, there are pathologic Q waves of
      variable depth and width together with ST elevation. The latter often fails to
      resolve despite an angiographically successful primary PCI. This article reviews
      the literature of ST resolution after reperfusion therapy, recent mechanistic
      insights on intra-myocardial haemorrhage gleaned from cardiac MRI, the patho
      physiology of STEMI including also findings from animal models, and the role of Q
      waves in characterising the evolution of STEMI towards its irreversible destiny.
      The MRI studies have correlated intra-myocardial haemorrhage with worse
      ventricular remodelling and worse outcome. A suggestion is made incorporating
      infarct-lead Q waves and time duration from symptom onset to discern whether late
      reperfusion attempts should be initiated or aborted. This suggestion should be
      confirmed through appropriate size randomized trials with mechanistic endpoints
      from serial MRI evaluations and, more importantly, with clinical endpoints on
      long-term outcome. Table 4 summarizes current STEMI guidelines for late
      presenting patients and Fig. 5 suggests potential future alterations. 

PMID- 25577766
TI  - Nocturnal effects of diurnal adaptive servo-ventilation therapy in patients with
      heart failure.

PMID- 25577765
TI  - Relationship between macular degeneration with prevalent heart failure: a cross
      sectional population study.

PMID- 25577767
TI  - Learning from mistakes: the case of drug-coated balloons.

PMID- 25577768
TI  - Coronary CT angiography evaluation of calcified coronary plaques by measurement
      of left coronary bifurcation angle.

PMID- 25577769
TI  - Resolution of ST depression after fibrinolysis can be more important than
      resolution of ST elevation for many patients with inferior STEMIs.

PMID- 25577770
TI  - A review on the Avicenna's contribution to the field of cardiology.
AB  - The cardiology and field of cardiovascular approaches are often mentioned as of
      the earliest concerns throughout the history of mankind civilization. During the
      golden ages of Islamic era, 9th to 12th centuries A.D., medical knowledge from
      various fields including cardiology was flourished by prominent Persian
      physicians and scholars. Among those outstanding physicians and scientists of the
      Islamic golden era, Avicenna is known as a famous and pioneer character. To
      outline the cardiovascular knowledge and contribution of Avicenna, current review
      compiled all his evidence-based concepts of cardiovascular findings from current
      medical literatures as well as those mentioned in his important medical
      encyclopedia, the Canon of Medicine. In this review, Avicenna's findings on
      cardiovascular anatomy such as his description of Willis circle, capillary
      circulation and arterial and ventricular contractions in the cardiovascular
      system have been mentioned. Also, his books and manuscripts on cardiology as well
      as findings and theories on cardiovascular and allied diseases were discussed.
      These findings are included in his descriptions on cardiac tamponade, stroke,
      palpitation, atherosclerosis, hypertension, association of the cardiovascular
      complications with erection and ejaculation, interaction between the heart and
      emotions as well as some of his mentioned drugs for cardiological disorders and
      the early concepts of drug targeting. These results can show Avicenna's great
      contribution to improve the sciences of cardiology in early medieval era. 

PMID- 25577771
TI  - Kounis syndrome: optical coherence tomography findings.

PMID- 25577773
TI  - A response to the letter by Liu et al.: the relationship between the giant
      ventricular diverticulum and ventricular premature beat.

PMID- 25577772
TI  - The development and feasibility of a composite score of echocardiographic indices
      that may stratify outcome in patients with diabetes mellitus.
AB  - BACKGROUND: Early detection of changes in cardiac structure and function
      associated with type 2 diabetes (T2DM) is important. However when multiple
      abnormalities are present, combining individual measurements can be subjective.
      This study sought to create a simple echo score that summarises measurements that
      may detect early and prognostically important changes in cardiac function.
      METHODS: Standard echocardiography was performed on 849 people with T2DM (median
      age 65years, 40% female, median duration of diabetes 5.5years). Principal
      components analysis was performed on measurements of LV mass, LA volume, E:e',
      and s', to create an objective summary score. The score was included in two Cox
      proportional hazard models adjusted for CV risk factors: one estimated the
      development of heart failure (HF) and the second estimated any CV event. RESULTS:
      The first two principal components represented 75% of the variation between the
      four echo measurements. A continuous score that represents the residual
      difference between these two components was derived that only requires
      measurement of medial E:e' and s'. The score was significantly associated with
      the development of HF within four years (hazard ratio 1.34; 95% CI 1.15, 1.56).
      CONCLUSIONS: We have developed a simple, objective score that enhances the use of
      echocardiography in the detection of sub-clinical cardiac disease in people with
      T2DM. Initial findings suggest that it may help identify those at increased risk
      of developing HF within four years.

PMID- 25577774
TI  - From culprit artery reperfusion to non-culprit revascularization: will ECG play a
      bigger role in the evolving STEMI care?

PMID- 25577775
TI  - Plasma angiopoietin-1 level, left ventricular ejection fraction, and multivessel
      disease predict development of 1-year major adverse cardiovascular events in
      patients with acute ST elevation myocardial infarction - a pilot study.
AB  - OBJECTIVES: Patients with acute myocardial infarction (AMI) are frequently
      complicated with major cardiovascular events (MACEs). Endothelial dysfunction has
      been found to be involved in pathogenesis of AMI, but its role in development of
      MACEs after AMI is not clearly investigated. This study aimed to determine
      whether the plasma markers of endothelial dysfunction could serve as independent
      predictors for MACEs in patients with AMI. METHODS: This prospective study was
      conducted from March 2010 to July 2012 and enrolled consecutive 132 patients with
      acute ST elevation myocardial infarction (STEMI) receiving primary percutaneous
      coronary intervention (PCI). Plasma levels of thrombomodulin (TM), von Willebrand
      factor (vWF), angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth
      factor (VEGF) were measured on day 1 of AMI. The development of MACEs at 1-year
      follow-up was recorded. RESULT: Patients with STEMI who developed MACEs had
      increased heart rate on admission (86+/-24 vs. 74+/-20bpm, p=0.006), lower left
      ventricular ejection fraction (LVEF) (49.0+/-12.4 vs. 57.2+/-12.4%, p=0.002), and
      higher incidence of multivessel disease (66.7% vs. 42.2%, p=0.018) comparing with
      those without MACEs. Plasma level of Ang-1 was lower in patients with MACEs than
      in those without (21,165+/-16,281 vs. 31,411+/-21,593pg/mL, p=0.018). In
      multivariate analysis, Ang-1 level<median value (OR 2.977, 95% CI 1.16-7.63,
      p=0.023), LVEF (OR 0.958, 95% CI 0.92-0.99, p=0.022) and multivessel disease (OR
      3.013, 95% CI 1.19-7.60, p=0.019) independently predicted 1-year MACEs.
      CONCLUSION: Decreased plasma Ang-1 levels on admission, LVEF and multivessel
      disease independently predicted the development of 1-year MACEs in patients with
      STEMI. These results suggest that endothelial dysfunction may play an important
      role in mediating MACEs in patients with STEMI.

PMID- 25577776
TI  - Treatment of pheochromocytoma blockade of MAPK pathway inhibition in the NF
      kappaB pathway and bFGF - effect of statins on pheochromocytoma patients.

PMID- 25577777
TI  - Low level non-invasive vagus nerve stimulation: a novel feasible therapeutic
      approach for atrial fibrillation.

PMID- 25577778
TI  - Does myocardial iron load determine the severity of heart insufficiency?

PMID- 25577779
TI  - Calcific Monckeberg's arteriosclerosis: an uncommon cause of radial access
      failure.

PMID- 25577780
TI  - Lord of the imaging rings - Takayasu's aortitis.

PMID- 25577781
TI  - Is the worse outcome associated with epinephrine in resuscitated patients due to
      Takotsubo syndrome?

PMID- 25577782
TI  - Effects of Celiprolol and Bisoprolol on Blood Pressure, Vascular Stiffness, and
      Baroreflex Sensitivity.
AB  - BACKGROUND: We tested the hypothesis that celiprolol and bisoprolol have
      differential effects on blood pressure (BP), flow-mediated dilation (FMD), and
      vascular stiffness. METHODS: We analyzed 102 hypertensives (mean age: 59+/-14
      years) who were being treated other than beta-blockers. They were randomized to
      receive add-on treatment with either celiprolol 100-200mg (C group) or bisoprolol
      2.5-5mg (B group), and followed up for 3 months. In addition to clinic, home, and
      ambulatory BP monitoring, the FMD, radial augmentation index (AI), brachial-ankle
      pulse wave velocity (baPWV), urine albumin-to-creatinine ratio, and baroreflex
      sensitivity (BRS) were measured at baseline and at the end of the study. RESULTS:
      Compared to the baseline values, home and 24-hour BP were significantly lowered
      in the third month in both groups (all Ps < 0.05). Pulse rate (PR) and baPWV were
      reduced (P < 0.001), and BRS was increased significantly only in the B group (P =
      0.02). Radial AI was unchanged in the C group but was significantly increased in
      the B group (P < 0.001). Central BP was significantly reduced in the C group (P =
      0.003) but was unchanged in the B group. FMD was significantly increased in both
      groups (both P < 0.01). CONCLUSION: Bisoprolol achieved the greater reduction of
      PR and improved BRS and vascular stiffness, whereas, celiprolol reduced the
      central BP level. In treated hypertensive patients, add-on use of celiprolol may
      be favorable in uncomplicated stage of hypertension. On the other hand,
      bisoprolol may be useful in hypertensives with cardiac or vascular diseases who
      have advanced atherosclerotic changes and sympathetic nervous system activation.

PMID- 25577784
TI  - Medicine as a profession: a hypothetical imperative in clinical ethics.

PMID- 25577783
TI  - Clostridium tertium bacteremia in a patient with glyphosate ingestion.
AB  - BACKGROUND: Clostridium tertium is distributed in the soil and in animal and
      human gastrointestinal tracts. C. tertium has been isolated from patients with
      blood diseases, immune disorders, and abdominal surgeries. Glyphosate is toxic,
      causing cause eye and skin irritation, gastrointestinal pain, and vomiting.
      Ingestion of herbicides modifies the gastrointestinal environment, which stresses
      the living organisms. However, there has been little attention to cases of
      bacteremia in patients recovering from suicide attempt by ingesting herbicide.
      CASE REPORT: Clostridium tertium was identified in a 44-year-old female who
      attempted suicide by glyphosate (a herbicide) ingestion. The 16S rRNA sequences
      from all colonies were 99% identical with that of C. tertium (AB618789) found on
      a BLAST search of the NCBI database. The bacterium was cultured on TSA under
      aerobic and anaerobic conditions. Antimicrobial susceptibility tests performed
      under both aerobic and anaerobic conditions showed that the bacterium was
      susceptible to penicillin, a combination of beta-lactamase inhibitor and
      piperacillin or amoxicillin, and first- and second- generation cephalosporins.
      However, it was resistant to third- and fourth-generation cephalosporins.
      CONCLUSIONS: Glyphosate herbicide might be a predisposing factor responsible for
      the pathogenesis of C. tertium. The results highlight the need for careful
      diagnosis and selection of antibiotics in the treatment of this organism.

PMID- 25577789
TI  - Topical Review: Applying Positive Development Principles to Group Interventions
      for the Promotion of Family Resilience in Pediatric Psychology.

PMID- 25577790
TI  - Effects of sawdust thickness on the growth performance, environmental condition,
      and welfare quality of yellow broilers.
AB  - An experiment was conducted to evaluate the effect of litter thickness on growth
      performance, immune status, environmental condition, and welfare quality in
      yellow broilers. In total, 1,800 one-day-old Suqin yellow broilers were raised
      for 21 d. On d 22, 1,600 birds of similar BW (404+/-12 g) were randomly selected
      and placed into 20 indoor pens (8 birds/m2, 10 m2/pen). These birds were assigned
      to a litter treatment of 4, 8, 12, and 16 cm. Each treatment was repeated in five
      pens. The results showed that a thicker litter was related to increased BW, daily
      weight gain, and daily feed intake (P<0.001). Feed conversion ratio and mortality
      were unaffected by litter thickness (P=0.320, P=0.353, respectively). Absolute
      and relative liver weights showed a significant linear response to increasing
      litter thickness (P=0.01, P=0.001, respectively). The litter moisture content,
      air ammonia, and CO2 content decreased, whereas the air dust content increased
      with increasing litter thickness (P<0.001, P=0.017, P=0.033, P<0.001,
      respectively). Litter thickness had no effect on gait, plumage damage, hock burn
      or breast skin crusting (P = 0.076, P=0.964, P=0.131, P=0.401, respectively).
      Plumage cleanliness, foot pad dermatitis, hock swelling and breast blister varied
      significantly with litter thickness (P=0.027, P=0.011, P=0.014, P=0.042,
      respectively). The results of this study suggest that an increasing litter
      thickness has a beneficial effect on the growth performance, environmental
      condition and welfare of birds.

PMID- 25577792
TI  - Immunobiological activity and antiviral regulation efforts of Chinese goose
      (Anser cygnoides) CD8alpha during NGVEV and GPV infection.
AB  - The CD8 molecule is a cell membrane glycoprotein expressed on cytotoxic T
      lymphocytes, which are involved in the clearance of viruses. However, the
      functional characterization of goose CD8alpha is still unclear. The
      immunobiological characterization of goose CD8alpha in goose spleen mononuclear
      cells (MNCs) was examined by real-time quantitative PCR (qPCR). It was shown that
      CD8alpha mRNA levels were significantly up-regulated by in vitro treatment of
      MNCs with phytohemagglutinin (PHA), concanavalin A (ConA), and polyinosinic
      polycytidylic acid (poly I:C) in a dose-dependent way, but lipopolysaccharides
      (LPSs) did not have this same effect. Moreover, the time-course effect of
      CD8alpha expression in response to mitogens (PHA, ConA, and poly I:C) was
      evaluated in MNCs. A significant increase in the transcriptional levels of
      CD8alpha was detected in new type gosling viral enteritis virus (NGVEV)-infected
      goose MNCs at 48 h postinfection (PI) and in goose parvovirus (GPV)-infected MNCs
      at 72 h PI. Also, the number of CD8alpha+ cells was significantly increased
      during viral infection from 72 h on. The seminal changes in mRNA profiles of
      antiviral cytokines (IFN-alpha, IFN-gamma, and IL-18) were observed and were
      significantly increased during late phases of NGVEV and GPV infection.
      Accordingly, our data not only contribute to the understanding of the immune
      characteristics of goose CD8alpha, but they also provide new insight into the
      innate antiviral immunity of geese.

PMID- 25577791
TI  - The transect method: a novel approach to on-farm welfare assessment of commercial
      turkeys.
AB  - Currently, no animal-based protocol for on-farm welfare assessment of commercial
      turkeys is available. The birds' size and flighty nature make obtaining a
      representative sample using traditional methods difficult. The transect walks
      (TW) approach provides a potential alternative for on-farm assessments of turkey
      welfare. We compared the TW approach with a traditional method, and data
      collected as the birds were moved out of the house during the load out process
      (L). Ten commercial 19- to 20-week-old Hybrid turkey flocks were evaluated (1
      flock/house/farm). Half of the flocks were housed on farms deemed as "faring
      well" by the company, the other half were on "suboptimal" farms. Each house was
      subdivided longitudinally into 4 transects. Two observers walked the transects in
      random order, recording the total number of birds per transect that were
      immobile; lame; aggressive towards a mate; interacting with humans; with visible
      head, vent, or back wounds; engaging in mounting behaviors; small; featherless;
      dirty; sick; terminal; or dead. Flocks were re-evaluated on the same day using
      the individual sampling method (S), where randomly selected birds were scored as
      they took 10 steps. Flocks were re-assessed within 48 h of the transect
      evaluation, as birds were funneled out of the house during load out. Using ANOVAs
      we determined the effects of observers, method, management, and their
      interactions on proportions of turkeys per house within each category. Outcome
      parameters were not affected by management (P>0.05 for all) or observer (P>0.05
      for most), but an assessment method effect was detected (P<0.05). S differed from
      the 2 other methods (P<0.05) for most parameters except aggression towards a
      mate, back wounds, dirty, sick, and vent wounds. Differences were not detected
      between data collected using TW and during L, except for dead (P=0.0007) and
      immobile (P=0.007). Results suggest that the TW method is a promising tool for on
      farm turkey welfare assessment as it produced results similar to those obtained
      at L when all birds could be scored individually.

PMID- 25577793
TI  - Prophylactic administration of a combined prebiotic and probiotic, or therapeutic
      administration of enrofloxacin, to reduce the incidence of bacterial
      chondronecrosis with osteomyelitis in broilers.
AB  - Bacteria entering the bloodstream via translocation from the gastrointestinal
      tract spread hematogenously and can trigger bacterial chondronecrosis with
      osteomyelitis (BCO) by infecting osteochondrotic microfractures in the epiphyseal
      physeal cartilage of the proximal femora and tibiae. In experiment 1, broilers
      were fed control feed or the same feed containing BacPack 2X, which includes the
      prebiotic IMW50 (a mannan oligosaccharide beta-glucan yeast cell wall product)
      plus the probiotic Calsporin (Bacillus subtilis C-3102). Broilers reared on wire
      flooring consistently developed higher incidences of BCO than hatchmates reared
      on wood shavings litter (>=24 vs. <=4%, respectively; P=0.001). Adding BacPack 2X
      to the feed on d 1 through 56 delayed the age of onset and reduced the cumulative
      incidence of BCO on wire flooring when compared with broilers fed the control
      feed (24.0 vs. 40.7%, respectively; P=0.003). In experiment 2, broilers reared on
      wire flooring received tap water on d 1 through 62 (control group) or therapeutic
      levels of the potent fluoroquinolone antimicrobial enrofloxacin in the water on d
      35 through 54 (enrofloxacin group). During enrofloxacin administration, half as
      many birds developed BCO in the enrofloxacin group when compared with the control
      group (8.1 vs. 19.5%, respectively, on d 35 through 54; P=0.001), whereas both
      groups had similar BCO incidences subsequent to withdrawing enrofloxacin on d 55
      through 62 (14.8 vs. 18.2% for the enrofloxacin vs. control groups; P=0.386).
      Cumulative lameness incidences for d 1 through 62 were higher for the control
      group than for the enrofloxacin group (39.0 vs. 25.8%, respectively; P=0.003).
      These results demonstrate that wire flooring imposes a rigorous challenge that
      leads to high incidences of BCO that can be difficult to suppress, even with
      therapeutic doses of enrofloxacin. Prophylactically adding BacPack 2X to the feed
      reduced the incidence of BCO lameness by a proportion similar to that achieved
      with enrofloxacin, indicating that probiotics potentially can provide effective
      alternatives to antibiotics for reducing BCO lameness attributable to bacterial
      translocation and hematogenous distribution.

PMID- 25577794
TI  - Selection for pro-inflammatory mediators produces chickens more resistant to
      Eimeria tenella.
AB  - We recently developed a novel selection method based on identification and
      selection of chickens with an inherently high and low phenotype of pro
      inflammatory mediators, including interleukin (IL)-6, CXCLi2, and CCLi2. The
      resultant high line of chickens is more resistant to Salmonella enterica serovar
      Enteritidis (Salmonella Enteritidis) compared to the low line. In the current
      study, we sought to determine if the high line birds were also more resistant to
      the protozoan parasite Eimeria tenella. In three separate experiments, 14-day-old
      chickens from the high and low lines were challenged orally with 10*10(3) to
      45*10(3) E. tenella oocysts. Birds were sacrificed 6 d postchallenge and the
      caeca was removed and scored for lesions and body weight gain compared to mock
      infected controls. The high line birds were more resistant to intestinal
      pathology as demonstrated by lower lesion scores (P<=0.04) compared to the low
      line. There were no differences in body weight gain between the lines. The
      results from this study showed that in addition to enhanced resistance against
      Salmonella Enteritidis, high line chickens are also more resistant to the
      pathology associated with coccidial infections compared to the low line birds.
      Taken together with our initial study utilizing the high and low lines, selection
      based on increased pro-inflammatory mediator expression produces chickens that
      are more resistant to both foodborne and poultry pathogens, including cecal
      pathology associated with costly coccidial infections.

PMID- 25577795
TI  - Changes in the protein secondary structure of hen's egg yolk determined by
      Fourier transform infrared spectroscopy during the first eight days of
      incubation.
AB  - In this study, incubation-induced alterations in the protein secondary structures
      of egg yolk and its major fractions (granules, plasma, and low-density
      lipoproteins [LDL]) were monitored during the first 8 d of embryogenesis using
      Fourier transform infrared spectroscopy (FTIR) and isoelectric focusing (IEF).
      Two factors potentially connected with egg yolk protein secondary structure
      changes were evaluated, i.e., the pH value of incubated egg yolk, and phosvitin,
      an important egg yolk protein assumed to play an important role in hematopoiesis
      as the iron carrier during early embryogenesis. However, neither the significant
      increase in pH value (6.07 to 6.92) of egg yolk during incubation of fertilized
      eggs, nor the release of iron from phosvitin were found to be directly related to
      the changes in protein secondary structure in egg yolk and its fractions. FTIR
      showed that the protein conformation in whole egg yolk, granules, and LDL was
      stable during incubation, but separate evaluation of the plasma fraction revealed
      considerable changes in secondary structure. However, it is unlikely that these
      changes were provoked by structure changes of the proteins originally present in
      plasma; instead, the physiological influx of albumen into the yolk sac was
      expected to play an important role in the protein modifications of egg yolk, as
      was shown both by FTIR and IEF of the water-soluble egg yolk proteins. Moreover,
      FTIR was used to determine the naturally occurring proportions (%) of the
      secondary structure elements in egg yolk and its 3 fractions on d 0 of
      incubation. The granules fraction mainly consisted of a mixture of inter- and
      intramolecular beta-sheets (57.04%+/-0.39%). The plasma fraction was found to
      consist mainly of alpha-helices (43.23%+/-0.27%), whereas LDL was composed almost
      exclusively of intramolecular beta-sheets (67.36%+/-0.56%) or beta-turns, or
      both. On the other hand, whole egg yolk was mainly composed of intermolecular
      beta-sheets (39.77%+/-0.48%), potentially indicating molecular interchanges
      between the individual fractions.

PMID- 25577796
TI  - Characterization of red-legged partridge (Alectoris rufa) sperm: Seasonal changes
      and influence of genetic purity.
AB  - The general decline in wild Iberian populations of the red-legged partridge
      (Alectoris rufa) has been accompanied by an increase in game-farm facilities
      producing hybrids with chukar partridges (Alectoris chukar). Genetic
      introgression from chukar partridges is thought to modify male red-legged
      partridge reproductive indicators. The aim of the present study was to determine
      the effects of such genetic introgression on seasonal reproductive patterns by
      comparing the sperm and plasma testosterone concentrations of males from pure red
      legged and hybrid red-legged/chukar populations. Semen was collected twice
      monthly over a 12-mo period using a massage technique. Both types of bird showed
      a clear seasonal pattern of spermatogenic activity. The proportion of males
      ejaculating sperm was higher (P<0.05) among the pure red-legged birds. The
      greatest sperm production was recorded in March to May among the pure birds and
      April to May among the hybrids. Reproductive activity in both groups decreased in
      June, to reach a minimum in August to December among the hybrids and in September
      to December among the pure birds. Spermatogenic activity resumed in January in
      both groups. The sperm concentration produced by the pure birds was smaller than
      that of the hybrids (P<0.001), but the percentage of motile sperm was higher in
      the pure birds (P<0.001). The sperm of the hybrids showed greater straight-line
      velocity (P<0.05), linearity (P<0.001), straightness (P<0.001), sperm wobble
      (P<0.05), and beat-cross frequency values (P<0.001). The length and area of the
      sperm head were smaller in the pure birds (P<0.05). The seasonal plasma
      testosterone concentration pattern followed a trend roughly parallel to the
      ejaculatory response. The present results suggest that genetic introgression
      influences the reproductive variables of the red-legged partridge.

PMID- 25577797
TI  - Association of novel polymorphisms of forkhead box L2 and growth differentiation
      factor-9 genes with egg production traits in local Chinese Dagu hens.
AB  - Transcription factor forkhead box L2 (FOXL2) and growth differentiation factor-9
      (GDF9) genes have critical roles in the regulation of hen ovarian development. In
      the present study, these genes were explored as possible molecular markers
      associated with BW, hen-housed egg production, and egg weight in Chinese Dagu
      hens. Samples were analyzed using the PCR-single strand conformation polymorphism
      (PCR-SSCP) technique followed by sequencing analysis, and two novel single
      nucleotide polymorphisms (SNPs) were identified within these candidate genes.
      Among them, an A/G transition at base position 238 in the coding region of the
      FOXL2 gene and a G/T transversion at base position 1609 in exon 2 of the GDF9
      gene were found to be polymorphic and named SNPs A238G and G1609T, respectively.
      The SNP A238G (FOXL2) leads to a nonsynonymous substitution (isoleucine77-to
      valine), and when the 360 Dagu hen samples were divided into genotypes AA and AB,
      allele A was found to be present at a higher frequency. Furthermore, the AA
      genotype correlated with significantly higher hen-housed egg production at 30,
      43, 57, and 66 wk of age and with a higher egg weight at 43 wk (P<0.05). For the
      SNP G1609T (GDF9), the hens were typed into TT and TC genotypes, with the T
      allele shown to be dominant. The TC genotype was also markedly correlated with
      higher hen-housed egg production and a higher egg weight (P<0.05). Moreover, four
      haplotypes were reconstructed based on these two SNPs, with the AATC haplotype
      found to be correlated with the highest hen-housed egg production at 30 to 66 wk
      of age and with higher egg weights at 43 wk (P<0.05). Collectively, the two SNPs
      identified in this study might be used as possible genetic molecular markers to
      aid in the improvement of egg production traits in chicken breeding.

PMID- 25577798
TI  - Reduced functionality of PSE-like chicken breast meat batter resulting from
      alterations in protein conformation.
AB  - The objectives of this study were to evaluate protein thermal stability, water
      protein interaction, microstructure, and protein conformation between PSE-like
      and normal chicken breast meat batters. Sixty pale, soft, and exudative (PSE)
      like (L*>53, pH24 h<5.7) and 60 normal (46<L*<53, 5.7<pH24 h<6.1) chicken breast
      meats were selected from 3 different occasions in a major Chinese commercial
      plant. Two different meat batters were formulated to 14% meat protein and 2%
      salt, and they were analyzed for the protein changes and the microstructure using
      differential scanning calorimetry, low-field (LF)-NMR, SEM, and Raman
      spectroscopy. PSE-like meat batter had lower gel strength, water-holding
      capacity, and salt-soluble protein extraction (P<0.05). Heated PSE-like meat
      batter formed an aggregated gel matrix, while normal meat batter produced a
      compact gel network with fine, cross-linked strands by many protein filaments. LF
      NMR revealed an increase in the water mobility in heated PSE-like meat batter
      with an increasing amount of loosely bound water (P<0.05). No significant changes
      were observed in the electrophoretic patterns of salt-soluble protein extracts by
      SDS-PAGE. However, differential scanning calorimetry showed that PSE-like meat
      had greater myosin and sarcoplasmic proteins/collagen denaturation (P<0.05). In
      PSE-like meat, actin denaturation was particular evident after salt addition
      (P<0.05) using differential scanning calorimetry. Moreover, Raman spectroscopy
      indicated that PSE-like meat batter had less unfolded alpha-helix and beta-sheet
      structure formation, reduced exposure of hydrophobic and tyrosine residues
      (P<0.05), and changes in the microenvironment of aliphatic residues and
      tryptophan, which affected salt-soluble protein extraction, gel properties, and
      water-holding capacity. In conclusion, the inferior functional properties of PSE
      like meat were attributed to not only myosin denaturation, but also actin
      denaturation after salt addition and different protein structural states.

PMID- 25577799
TI  - Relationship between pectoralis major muscle histology and quality traits of
      chicken meat.
AB  - A trial was conducted to evaluate the influence of myodegeneration of pectoralis
      major muscle on quality traits and chemical composition of breast meat of heavy
      size male broilers. For this purpose, a total of 72 pectoralis major muscles were
      randomly collected from broilers farmed under homogeneous conditions and graded
      into three categories (mild, n=22; moderate, n=33; and severe, n=17) based on the
      presence of abnormal fibers (giant fibers, fibers with hyaline degeneration, and
      damaged and/or necrotic fibers) evaluated by histological and immunohistochemical
      analysis. Color, pH, drip loss, Allo-Kramer shear values, and chemical
      composition (moisture, proteins, total lipids, ashes, and collagen) were
      determined on nonmarinated breast meat. Purge loss and cook loss, total yield,
      and Allo-Kramer shear values were measured on vacuum-tumbled samples. Samples
      showing moderate myodegeneration had the highest mean cross-sectional area of the
      fibers, while samples with severe myodegeneration had myofibers of different
      diameter and without the characteristic polygonal shape, multifocal degeneration
      and necrosis, as well as infiltration of CD3-immunoreactive cells. Cooking losses
      of nonmarinated meat were lower in the mild group with respect to moderate and
      severe groups (21.4 vs. 24.7 and 24.7%; P<0.001). Breast muscles with severe
      damage, in comparison with mild degenerated samples, showed higher moisture (75.4
      vs. 74.4%; P<0.05) and lower protein percentages (21.1 vs. 22.6%; P<0.001). The
      lipid percentage of severely degenerated samples was higher than that from
      moderate group (2.94 vs. 2.36; P<0.05), while collagen content was not modified
      by histological lesion levels. Marinated meat from the mild group had higher
      uptake and total marinade yield after cooking. In conclusion, almost all breast
      fillets of heavy broiler chickens produced under intensive farming systems had
      histological lesions, which reflected on the chemical composition of the meat and
      the impaired water holding/binding capacities of the meat.

PMID- 25577800
TI  - Development of an absorbance-based response model for monitoring the growth rates
      of Arcobacter butzleri as a function of temperature, pH, and NaCl concentration.
AB  - In this study, the growth of Arcobacter butzleri in poultry was evaluated as a
      function of storage temperature (5, 22.5, and 40 degrees C), pH (5, 7, and 9),
      and NaCl concentration (0, 4, and 8%). A predictive model was developed using the
      absorbance-based response surface methodology to describe the growth rate. The
      primary model was obtained to predict a growth rate with a good fit (R2>=0.95),
      and the secondary model was obtained by nonlinear regression analysis and
      calculated as follows: Growth rate=-2.267274-0.024181 (Temp)+0.6459384
      (pH)+0.1926227 (NaCl)+0.0024661 (Temp*pH)-0.001312 (Temp*NaCl)-0.018802
      (pH*NaCl)+0.000467 (Temp2)-0.041711 (pH2)- 0.007426 (NaCl2). Our data showed that
      the growth of A. butzleri can be completely inhibited at a pH of 5 (in the
      absence of NaCl, at 5 degrees C) and at a pH of 9 (in the presence of 8% NaCl, at
      5 degrees C). The surface response model was statistically significant, with
      P<0.0001, as evident from the Fisher F test and from coefficient determination
      (R2, 0.95). This model was also verified by the bias factor (Bf, 0.839), accuracy
      factor (Af, 1.343), and mean square error (MSE, 0.0138). The newly developed
      secondary models of growth rate for A. butzleri could possibly be incorporated
      into a tertiary modeling program such as Pathogen Modeling Program (U.S.
      Department of Agriculture [USDA]) and Food Micro Model (in the United Kingdom).
      As a result, they could be used to predict the growth kinetics of A. butzleri as
      a function of a combination of environmental factors. Ultimately, the developed
      model can be used to reduce A. butzleri in poultry production, processing, and
      distribution, thereby enhancing food safety.

PMID- 25577803
TI  - [Lower G.I./colon and rectum cancer].

PMID- 25577804
TI  - [Molecular biomarkers to predict outcome in colorectal cancer- current evidence
      and future perspectives].

PMID- 25577801
TI  - Phagocytosis of platelets enhances endothelial cell survival under serum
      deprivation.
AB  - Platelets are key players in fundamental processes of vascular biology, such as
      angiogenesis, tissue regeneration, and tumor metastasis. However, the underlying
      mechanisms remain unclear. In this study, some tumor vascular endothelial cells
      were positively stained by antiplatelet antibodies. Further investigation
      revealed that platelets were taken up by endothelial cells in vitro and in vivo.
      Human umbilical vascular endothelial cells were rendered apoptotic under
      conditions of serum deprivation. However, endothelial apoptosis was suppressed
      and cell viability was enhanced when platelets were added to the cultures.
      Endothelial survival was paralleled by an upregulation of phosphorylated Akt and
      p70 S6K. In conclusion, this study demonstrated that platelets can be
      phagocytosed by endothelial cells, and the phagocytosed platelets could suppress
      endothelial apoptosis and promote cell viability level. The mechanism underlying
      this process involves the activation of Akt signaling. 

PMID- 25577805
TI  - [First-line chemotherapy for unresectable and metastatic colorectal cancer].

PMID- 25577806
TI  - [Perioperative chemotherapy for advanced rectal cancer].

PMID- 25577807
TI  - [Reception and adjuvant chemotherapy for metastatic site of colorectal cancer].

PMID- 25577808
TI  - Why education matters.

PMID- 25577802
TI  - Thyroid hormone alleviates demyelination induced by cuprizone through its role in
      remyelination during the remission period.
AB  - Multiple sclerosis (MS) is a disease induced by demyelination in the central
      nervous system, and the remission period of MS is crucial for remyelination. In
      addition, abnormal levels of thyroid hormone (TH) have been identified in MS.
      However, in the clinic, insufficient attention has been paid to the role of TH in
      the remission period. Indeed, TH not only functions in the development of the
      brain but also affects myelination. Therefore, it is necessary to observe the
      effect of TH on remyelination during this period. A model of demyelination
      induced by cuprizone (CPZ) was used to observe the function of TH in
      remyelination during the remission period of MS. Through weighing and behavioral
      tests, we found that TH improved the physical symptoms of mice impaired by CPZ.
      Supplementation of TH led to the repair of myelin as detected by
      immunohistochemistry and western blot. In addition, a sufficient TH supply
      resulted in an increase in myelinated axons without affecting myelin thickness
      and g ratio in the corpus callosum, as detected by electron microscopy. Double
      immunostaining with myelin basic protein and neurofilament 200 (NF200) showed
      that the CPZ-induced impairment of axons was alleviated by TH. Conversely,
      insufficient TH induced by 6-propyl-2-thiouracil resulted in the enlargement of
      mitochondria. Furthermore, we found that an adequate supply of TH promoted the
      proliferation and differentiation of oligodendrocyte lineage cells by
      immunofluorescence, which was beneficial to remyelination. Further, we found that
      TH reduced the number of astrocytes without affecting microglia. Conclusively, it
      was shown that TH alleviated demyelination induced by CPZ by promoting the
      development of oligodendrocyte lineage cells and remyelination. The critical time
      for remyelination is the remission period of MS. TH plays a significant role in
      alleviating demyelination during the remission period in the clinical treatment
      of MS. 

PMID- 25577809
TI  - Ebola, dogs and a vaccine.

PMID- 25577810
TI  - AVA's Animal Welfare Trust research grants.

PMID- 25577811
TI  - Positive trend in responsible use of antibiotics.

PMID- 25577812
TI  - Update on Middle East respiratory syndrome  coronavirus (MERS-CoV).

PMID- 25577814
TI  - Thinking fast and slow.

PMID- 25577813
TI  - Use of Tri-Solfen in sheep  and other food-producing animals.

PMID- 25577815
TI  - Re: Prevalence of Echinococcus granulosus  in Tasmanian dogs.

PMID- 25577816
TI  - Noninvasive prenatal cell-free fetal DNA-based screening for aneuploidies other
      than trisomy 21.

PMID- 25577817
TI  - Denture wear during sleep, pneumonia may be linked, researchers report.

PMID- 25577818
TI  - JADA CE to move to online-only access.

PMID- 25577819
TI  - Salivary gland cancer risk and BRCA gene mutations may be linked, study finds.

PMID- 25577820
TI  - Enhanced ICU oral care may reduce risk of lower respiratory tract infection,
      study shows.

PMID- 25577821
TI  - Fecal DNA analysis for colorectal cancer screening.

PMID- 25577822
TI  - Quantitative electroencephalography as a diagnostic aid for attention
      deficit/hyperactivity disorder in children.

PMID- 25577823
TI  - Critical issues in robotic surgery.

PMID- 25577824
TI  - Gene expression profiling in women with lymph node-negative breast cancer to
      select adjuvant chemotherapy.

PMID- 25577825
TI  - Percutaneous mitral valve repair.

PMID- 25577826
TI  - Percutaneous left atrial appendage closure therapy for the prevention of stroke.

PMID- 25577827
TI  - Intra-articular hyaluronic acid for osteoarthritis of the knee.

PMID- 25577828
TI  - AAFP should support HIV screening for all 15- to 17-year-olds. Author reply.

PMID- 25577829
TI  - [Long noncoding RNAs in prostate cancer].
AB  - Long non-coding RNAs (lncRNAs) are a group of RNA molecules which are longer than
      200 nucleotides. They do not have functional open reading frames and cannot
      encode proteins. Recent studies have demonstrated that lncRNAs are widely
      involved in the regulation of gene expression network at epigenetic,
      transcriptional and post-transcriptional levels, which may affect the growth,
      proliferation, differentiation, metabolism, apoptosis and other important
      physiological processes of cells. The abnormal expression of lncRNAs is closely
      associated with the development, invasion, metastasis and prognosis of tumors.
      The development of prostate cancer is a multi-factor and multi-step process, in
      which abnormal gene expression may play an important role. This review focuses on
      the recent progress in the studies on the role of lncRNAs in prostate cancer,
      aiming for some new clues to the clinical prevention, diagnosis and treatment of
      this malignancy.

PMID- 25577830
TI  - [Long-term benefit of male circumcision to the reduction of urinary tract
      infections and genitourinary cancers in China].
AB  - Increasingly accumulated results from randomized controlled trials and other
      clinical studies have demonstrated that male circumcision reduces the risks of
      acquisition and transmission of HIV, HPV, HSV-2, and other sexually transmitted
      infections, and thus has a potential role in preventing cervical cancer, penile
      cancer and prostate cancer. The prevalence of male circumcision in China is
      currently less than 5%. The clinical evaluation studies and randomized controlled
      trials of the Shang Ring device showed excellent safety profiles, extremely high
      acceptability, and satisfaction among the participants and service providers in
      Africa and China. Given the recent recommendations by the World Health
      Organization and the Joint United Nations Program on HIV/AIDS (UNAIDS), voluntary
      medical male circumcision should be promoted in China at the national level as an
      important alternative intervention to reduce reproductive tract infections and
      prevent both males and females from reproductive tract cancers. More emphasis is
      required on the studies of the long-term health benefits of male circumcision in
      uro-andrology.

PMID- 25577831
TI  - [Expression of recombinant human ZP3 protein using the baculovirus expression
      system].
AB  - OBJECTIVE: To investigate the methods and solve the technical bottlenecks in the
      preparation of recombinant human protein hZP3 using the baculovirus expression
      system and pave the technical ground for the production and application of
      recombinant hZP3. METHODS: The recombinant vector pFASTBAC HTa-hZP3 was
      constructed and transferred to competent E. coli cells carrying bacmid to produce
      recombinant bacmid by homologous recombination. Sf9 cells were transfected with
      the recombinant bacmid to produce recombinant baculovirus. Full-length
      recombinant hZP3 (amino acids 1-424) and truncated recombinant hZP3 (amino acids
      23-348) were expressed in the sf9 cells by infection with the recombinant
      baculovirus. The expression time of hZP3 was determined by Western blot and its
      purification was explored. RESULTS: The recombinant bacmid and baculovirus were
      successfully constructed for expressing both the full-length and truncated hZP3.
      The maximal expression of recombinant hZP3 in the sf9 cells was achieved at 72-96
      hours after baculovirus infection. Some of the recombinant hZP3 with His-tag
      could bind affinity matrix and got purified but most of the solubilized hZP3
      passed through and the reasons remained unknown. Purified recombinant hZP3
      labeled with Dylight Dye488 was able to bind human sperm. CONCLUSION: It is
      feasible to express recombinant hZP3 in insect cells using the baculovirus system
      though the yield of hZP3 needs to be optimized. The methods for efficient
      enrichment and purification of recombinant hZP3 require further exploration.

PMID- 25577832
TI  - [The highly expressed secreted phosphoprotein 1 gene in prostate cancer
      metastasis: a microarray-based bioinformatic analysis].
AB  - OBJECTIVE: To investigate the composition, function, and regulatory mechanisms of
      the secreted phosphoprotein 1 (SPP1) gene in metastatic prostate cancer. METHODS:
      We obtained the data about the whole genomic expression profiles on prostate
      cancer metastasis from the GEO database, and performed data-mining and
      bioinformatic analysis using BRB-Array Tools and such softwares as Protparam,
      MotifScan, SignalP 4.0, TMHMM, NetPhos2.0, PredictProtein, GO, KEGG, and STRING.
      RESULTS: Totally, 73 co-expressed differential genes in prostate cancer
      metastasis were identified, 21 up-regulated and 52 down-regulated (P <0.01).
      Bioinformatic analysis indicated that the highly expressed SPP1 gene encoded 314
      amino acids and contained 2 N-glycosylation sites, 8 casein kinase II
      phosphorylation sites and 3 protein kinase C phosphorylation sites, playing
      essential roles in extracellular matrix (ECM) binding, ossification, osteoblast
      differentiation, cell adhesion, PI3K-Akt signaling pathway, focal adhesion, Toll
      like receptor signaling pathway, and ECM-receptor interaction. CONCLUSION: The
      bioinformatic method showed a high efficiency in analyzing microarray data and
      revealing internal biological information. SPP1 may play an important role in
      prostate cancer metastasis and become a novel biomarker for the diagnosis of
      prostate cancer metastasis and a new target for its treatment.

PMID- 25577833
TI  - [Single nucleotide polymorphisms of the DGKK gene and hypospadias in Chinese
      children].
AB  - OBJECTIVE: To investigate the role of single nucleotide polymorphisms of the gene
      of diacylglycerol kinase kappa (DGKK) in hypospadias in Chinese children.
      METHODS: We performed direct sequencing on 2 hypospadias-related candidate single
      nucleotide polymorphisms of the DGKK gene (rs1934179 and rs7063116, never
      previously reported in the Chinese population) from 300 children with sporadic
      hypospadias and 200 healthy controls, and compared the results between the two
      groups. RESULTS: The mutation frequencies of rs1934179 and rs7063116 were 5.0%
      (15/300) and 5.67% (17/300) respectively in the hypospadias patients,
      significantly higher than 1.5% (3/200) and 2.0% (4/200) in the normal controls (P
      <0.05). The mutation frequencies of rs1934179 and rs7063116 in the cases of
      distal and middle hypospadias were also remarkably higher (6.5%, [13/200] and
      7.5% [15/200], P <0.05), but those in the proximal cases (both 2.0% [2/100])
      showed no statistically significant difference from the control (P >0.05).
      CONCLUSION: The polymorphisms of the DGKK gene may be associated with
      hypospadias, particularly distal and middle hypospadias, in Chinese children.

PMID- 25577834
TI  - [Location of semen collection and semen quality: clinic-collected versus home
      collected samples].
AB  - OBJECTIVE: To investigate the differences in semen quality between samples
      collected by masturbation in the clinic and at home. METHODS: Based on the WHO
      guidelines, we analyzed the ejaculates collected by masturbation in the clinic
      and at home from 342 men under infertility assessment and measured the contents
      of such biochemical markers in the seminal plasma as neutral alpha-glucosidase,
      zinc, and fructose. According to the location of semen collection, we divided the
      samples into two groups, clinic-collected and home-collected, and analyzed the
      differences in the semen parameters between the two groups with the SPSS 16.0
      software. RESULTS: Compared with the clinic-collected semen, the home-collected
      samples had significantly higher mean values in semen volume (4.0 vs 4.9%), sperm
      concentration (41 vs 64 x 10(6)/ml), total sperm count (175 vs 270 x 10(6) per
      ejaculate), progressive sperm motility (40 vs 52%), total count of progressively
      motile sperm (82 vs 135 x 10(6) per ejaculate) (all P <0.05). No significant
      differences were found between the two groups in normal sperm morphology (4.0 vs
      5.0%) and the contents of neutral alpha-glucosidase (26 vs 24 mU per ejaculate),
      zinc (8.0 vs 8.0 MUmol per ejaculate), and fructose (62 vs 60 MUmol per
      ejaculate) (all P >0.05). Abnormal sperm concentration (<20 x 10(6)/ml) was
      observed in significantly fewer of the home-collected samples than the clinic
      collected ones (18% [62/342] vs 30% [103/342], P<0.05), and so was abnormal
      progressive sperm motility (<32%) (64% [219/342] vs 75% [256/342], P<0.05).
      CONCLUSION: Our findings show that semen samples collected by masturbation at
      home has a higher quality than those collected in the clinic. So the location of
      semen collection should be taken into consideration in infertility investigation.

PMID- 25577836
TI  - [Comparison of ultrasound-guided transrectal and transperineal prostate biopsies
      in clinical application].
AB  - OBJECTIVE: To compare the positive rates and complications of ultrasound-guided
      transrectal and transperineal prostate biopsies. METHODS: We retrospectively
      analyzed 156 cases of ultrasound-guided transrectal (n = 97) and transperineal (n
      = 59) prostate biopsy, and compared the positive rate and post-biopsy
      complications between the two approaches. RESULTS: The positive rates in the
      transrectal and transperineal groups were 48.4% and 44.1%, respectively, with no
      significant difference between the two approaches according to different PSA
      levels (P >0.05). No statistically significant differences were observed between
      the transrectal and transperineal groups in the post-biopsy incidence rates of
      such complications as hematuria (54.6% vs 42.4%, P >0.05), lower urinary tract
      symptoms (17.5% vs 22.0%, P >0.05), dysuria (9.3% vs 6.8%, P >0.05), and acute
      urinary retention (7.2% vs 6.8%, P >0.05). However, the incidence rates of post
      biopsy infection and rectal bleeding were remarkably higher (15.5% vs 3.4%,
      P<0.05 and 50.5% vs 3.4%, P >0.01) while that of perineal swelling markedly lower
      in the former than in the latter (3.1% vs 13.6%, P <0.05). CONCLUSION:
      Transrectal and transperineal biopsies are both effective for the diagnosis of
      prostate cancer. Since their complications vary, the choice between the two
      methods depends on the specific condition of the patient.

PMID- 25577835
TI  - [Organic erectile dysfunction and metabolic syndrome in young and middle-aged
      men: analysis of 154 cases].
AB  - OBJECTIVE: To investigate the association of erectile dysfunction (ED) with
      metabolic syndrome ( MS) and the total testosterone ( tT) level in young and
      middle-aged men. METHODS: This study included 154 organic ED outpatients aged 20 
      59 years and 103 age-matched men with normal sexual life. We obtained their waist
      circumference ( WC) , blood pressure ( BP) , fasting blood glucose ( FBG) ,
      triglyceride ( TG) , high density lipoprotein ( HDL) , tT, IIEF -5 score,
      erectile function indexes and other relevant variables, and compared them between
      the ED and non-ED groups as well as between the ED patients with MS and those
      without MS. RESULTS: The prevalence of MS was significantly higher in the ED
      patients than in the non-ED males ( 40. 9 vs 17.4%, P < 0. 01). Statistically
      significant differences were found between the ED and non-ED groups in WC ( [90.
      80 +/-4. 90] vs [87. 70 +/-4. 60] em, P <0.01), SBP ([134.40+/-14.40] vs
      [129.90+/-12.40] mmHg, P<O.OS), DBP ([86.20+/-7.80] vs [83.60+/-8.60] mmHg, P
      <0.05), FBG ( [5.48 +/-1.02] vs [5. 11 +/-0. 91] mmol, P <0. 01), HDL ( [ 1.12 +/
      0. 27] vs [ 1. 26 +/-0. 29] mmol, P < 0. 01) , and tT ( [ 15. 98 +/- 6. 55] vs [
      17. 95 +/- 7. 39] mmol, P < 0. 05) , as well as between the ED patients with MS
      and those without MS in such erectile function indexes as tT ( [ 14.49 +/-6. 23]
      vs [ 17.01 +/-6. 60] mmol, P <0. 05), erectile penile circumference ( [9. 67 +/-
      1.09] vs [10.16 +/- 1.01] cm, P <0. 01), erectile penile length ( [ 10.40 +/- 1.
      20] vs [ 10.79 +/- 1. 07] cm, P <0. 05), glans temperature ( [ 31. 33 +/- 0. 65]
      vs [ 31. 80 +/- 0. 82]  degrees C , P < 0. 01) , and mean axial hardness of the
      penis ( [ 332. 60 +/- 137. 90] vs [ 419. 20 +/- 145. 80] g, P < 0. 01 ) . WC was
      significantly correlated with the incidence of ED ( P < 0. 01 ) . CONCLUSION: The
      prevalence of MS is significantly higher in young and middle-aged ED patients
      than in normal males, and MS is associated with a lower testosterone level and
      poorer erectile performance. Central obesity is closely correlated with ED in
      young and middle-aged men.

PMID- 25577837
TI  - [Clinical outcomes of fresh versus cryopreserved-thawed embryo transfer in high
      risk patients with ovarian hyperstimulation syndrome].
AB  - OBJECTIVE: To compare the clinical outcomes of fresh embryo transfer and
      cryopreserved-thawed embryo transfer in high-risk patients with ovarian
      hyperstimulation syndrome (OHSS). METHODS: We retrospectively analyzed the
      clinical data of 1784 high-risk OHSS patients undergoing IVF-ET, who were divided
      into groups A (n=939) and B (n=845). The former received fresh embryo transfer
      and the latter cryopreserved-thawed embryo transfer. We compared gonadotropin
      (Gn) administration, body mass index (BMI), the prevalence of polycystic ovary
      syndrome (PCOS), the number of oocytes retrieved, and the rates of clinical
      pregnancy, embryo implantation and OHSS incidnece between the two groups.
      RESULTS: Totally, 657 (69.97%) and 586 (69.35%) pregnancies were achieved in
      groups A and B, respectively, with 33 cases of moderate OHSS (3.5%) in the former
      and 30 (3.6%) in the latter. The prevalence of PCOS, the E2 level at hCG trigger,
      the number of oocytes retrieved, the number of mature oocytes, and the number of
      quality embryos were significantly lower in group A than in B (P <0.01). No
      statistically significant differences were found between the two groups in age,
      infertility duration, BMI, Gn administration, embryo implantation rate, clinical
      pregnancy rate, abortion rate, and OHSS incidence (P >0.05). CONCLUSION: In IVF
      ET cycles, cryopreserved-thawed embryo transfer does not influence the clinical
      outcome in high-risk OHSS patients and can avoid the incidence of severe OHSS.

PMID- 25577838
TI  - [Functional outcomes of transvesical single-site versus extraperitoneal
      laparoscopic radical prostatectomy for low-risk prostate cancer].
AB  - OBJECTIVE: To compare the perioperative data, pathological results and functional
      outcomes of transvesical single- site laparoscopic radical prostatectomy
      (TVSSLRP) with those of nerve-sparing extraperitoneal laparoscopic radical
      prostatectomy (nsELRP) in the treatment of low-risk prostate cancer (PCa).
      METHODS: Fifty patients with low-risk organ-confined PCa were randomly assigned
      to two groups of equal number to receive TVSSLRP and nsELRP, respectively.
      Comparisons were made between the two groups of patients in such demographic and
      baseline data as age, comorbidity, body mass index (BMI), serum prostate-specific
      antigen (PSA), prostate volume, bioptic Gleason score, clinical stage, IIEF-5
      score, nocturnal penile tumescence (NPT), penile brachial index (PBI), and penile
      arterial blood flow velocity as well as in such surgery-related parameters as
      operation duration, blood loss, blood transfusion, intraoperative complications,
      positive surgical margin, catheterization time, hospital stay, and postoperative
      Gleason score, pathologic stage, urinal pad use, PSA level, IIEF-5 score, NPT,
      PBI and PABFV. RESULTS: All the operations were successfully performed. There
      were no statistically significant differences between the two groups either in
      the demographic and baseline data or in intraoperative blood loss, blood
      transfusion rate, complications, and positive surgical margin. No intraoperative
      complications and positive surgical margins were found in either group. Compared
      with nsELRP, TVSSLRP achieved a significantly shorter operation duration ([151.46
      +/- 40.68] min vs [105.92 +/- 26.21] min, P <0.05), catheterization time ([13.01
      +/- 1.64] d vs [11.24 +/- 1.17] d, P <0.05), and hospital stay ([15.76 +/- 4.65]
      d vs [12.92 +/- 4.29] d, P <0.05). On the first day and at 1, 3 and 6 months
      after catheter removal, the urinary continence rates in the TVSSLRP and nsELRP
      groups were 84% vs 52% (P <0.05), 100% vs 84%, 100% vs 96%, and 100% vs 96%,
      respectively; and at 3, 6 and 12 months after surgery, the erectile potency rates
      were 48% vs 28% (P <0.05), 64% vs 52%, and 76% vs 68%, respectively, with an IIEF
      5 score >= 18, all evidently higher in the TVSSLRP than in the nsELRP group. The
      penile brachial index and arterial blood flow velocity of the two groups of
      patients exhibited no significant differences before and after surgery, nor did
      postoperative complications (grade II) between the TVSSLRP and nsELRP groups (32%
      vs 40%, P >0.05). The Gleason score and pathologic stage were increased after
      surgery, but with remarkable differences between the two groups (P >0.05). No
      biochemical recurrence was found in either group during a 12-month follow-up.
      CONCLUSION: With the advantages of safety and rapid postoperative recovery, both
      TVSSLRP and nsELRP are feasible for the treatment of low-risk organ-confined PCa,
      but the former may achieve an earlier recovery of urinary continence and erectile
      function than the latter.

PMID- 25577839
TI  - [Testis-sparing surgery for benign testicular tumor].
AB  - OBJECTIVE: To investigate the safety and feasibility of testis-sparing surgery
      (TSS) in the treatment of testicular tumor. METHODS: We retrospectively analyzed
      the clinical data of 8 cases of benign testicular tumor treated by TSS in our
      hospital from October 2005 to March 2012. RESULTS: The 8 patients, aged 18-67
      (mean 45) years, were preoperatively diagnosed with benign testicular tumor and
      all underwent partial testis resection. Rapid intraoperative pathology showed the
      incisal margins to be negative. Postoperative pathological examination confirmed
      Sertoli cell tumor in 3 cases, adenomatoid tumor in another 3, and mature
      teratoma in the other 2. The patients were followed up for 6 months to 7 years
      (mean 4 years), which revealed no relapse and metastasis, nor significant
      differences from the baseline in the testosterone level, IIEF score, and routine
      semen parameters. CONCLUSION: Testis-sparing surgery is one of the effective
      options for the management of benign testicular tumor, which can maximally
      preserve the testis tissue and protect the patient's sexual function.

PMID- 25577840
TI  - [Transumbilical single-site laparoscopic orchiopexy for inguinal cryptorchidism
      in children: report of 33 cases].
AB  - OBJECTIVE: To explore the feasibility and effect of transumbilical single-site
      laparoscopic surgery in the treatment of inguinal cryptorchidism in children.
      METHODS: From August to November 2013, 33 children with inguinal cryptorchidism
      (41 testes) underwent transumbilical single-site laparoscopic orchiopexy. The
      undescended testes were palpable in the inguen intra-operatively in all the
      cases, 14 on the right, 11 on the left, and 8 bilaterally. RESULTS: All the
      operations were performed successfully with neither intraoperative complications
      nor conversion to operi surgery. Adequate length of spermatic cord was pulled
      down to allow the testis to descend through the inguinal canal into the scrotum
      in all the cases. Totally, 39 testes in 31 cases were fixed at the bottom and 2
      testes in 2 cases in the middle of the scrotum. Follow-up ranged from 6 to 9
      months, which showed normal development of the testes, but no such postoperative
      complications as testicular retraction and atrophy, indirect hernia, and
      hydrocele. CONCLUSION: Transumbilical single-site laparoscopic orchiopexy is a
      feasible and effective technique for the treatment of inguinal palpable
      undescended testis in children, and its cosmetic results were desirable.

PMID- 25577841
TI  - [Yimusake Tablet: safe and efficacious for premature ejaculation].
AB  - OBJECTIVE: To objectively evaluate the efficacy and safety of Yimusake Tablet in
      the treatment of premature ejaculation (PE) through a multi-centered large-sample
      trial. METHODS: We conducted a multi-centered, open, fixed-dose, and self
      compared clinical trial among 300 patients with diagnosed PE. The trial lasted 12
      weeks, including 4 weeks without any medication and 8 weeks of treatment with
      Yimusake Tablet, 2 pills (1 g) per night. We observed the intravaginal
      ejaculation latency time (IELT) before and after treatment, evaluated the safety
      of medication, and performed a questionnaire investigation on the patients'
      satisfaction. RESULTS: Of the 300 PE patients, 288 accomplished the clinical
      trial. The patients ranged in age from 22 to 60 years, averaging at 31.6 years.
      The mean IELT of the patient was 62.5 seconds at baseline, 168.9 seconds after 4
      weeks of treatment with Yimusake Tablet, and 222.2 seconds after 8 weeks of
      medication. Among the 157 patients with normal erectile function (IIEF >21), the
      mean IELT was 71.4 seconds before treatment, 147.4 seconds after 4 weeks of
      medication, and 172.5 seconds after 8 weeks of medication. The patients'
      satisfaction was significantly increased after treatment. Those complicated by
      mild to moderate erectile dysfunction achieved different degrees of improvement
      in the IIEF-5 score, with a mean increase of 3.8. Only a few patients experienced
      mild adverse events, including constipation, dry mouth, nose bleeding, abdominal
      pain, and lumbosacral pain, which were all relieved without drug withdrawal.
      CONCLUSION: Yimusake Tablet is a safe and effective medicine for the treatment of
      PE.

PMID- 25577842
TI  - [Dysplasia of the fibrous sheath in human sperm: an update].
AB  - The ultrastructural abnormalities of human sperm flagella can cause sperm
      movement disorders. Dysplasia of the fibrous sheath (DFS) is an autosomal
      recessive genetic disease. The affected sperm in 95-100% of the patients display
      short, thick and irregular tails. Transmission electron microscopy can be used to
      confirm the diagnosis, which reveals gross abnormal flagella, with hypertrophy
      and hyperplasia of the fibrous sheath, without orderly disposition in
      longitudinal columns and transversal ribs. The axoneme shows variable distortion
      or almost complete obliteration. Microtubular doublets may exhibit partial or
      total lack of dynein arms. The genetic etiology of DFS is not yet clear. DFS does
      not affect the rates of fertilization and clinical pregnancy in ICSI, but due
      attention should be paid to the genetic risks in the offspring of the patient.

PMID- 25577843
TI  - [Positron emission tomography for molecular imaging of prostate cancer].
AB  - Prostate cancer is the most common malignancy in the urinary system of males. The
      remarkable biological and clinical heterogeneity of prostate cancer poses
      challenges to the initial diagnosis, differential diagnosis, treatment, and
      prognosis of the disease. Positron emission tomography/computed tomography
      (PET/CT) is an ideal imaging tool for noninvasive interrogation of underlying
      tumor biology. Recently, there are a variety of molecular imaging paths and
      radiopharmaceuticals for the diagnosis and treatment of prostate cancer. This
      article reviews the current state and prospects of the application of PET in the
      diagnosis of prostate cancer.

PMID- 25577844
TI  - [Genes associated with hypospadias: an update].
AB  - Hypospadias is one of the most common congenital malformations, and its main
      clinical manifestation is the abnormal opening of the urethra. Etiologically, it
      can be attributed to many factors, mainly including genetic, hormonal, and
      environmental factors. Recently studies about its genetic etiologies have found a
      variety of hypospadias-associated genes from the aspects of epidemiology and
      polymorphism, mainly those involving the formation of the penis, the development
      of the testis, the anabolism of androgens, and so on. This review focuses on the
      progress in the studies on the genetic etiology of hypospadias.

PMID- 25577845
TI  - [Scrotal calculi: advances in clinical research].
AB  - Scrotal calculi are freely mobile calcified bodies or stones located between the
      layers of the tunica vaginalis of the testis. The literature on this relatively
      rare benign lesion consists mostly of case reports. In most cases, scrotal
      calculi are found incidentally during ultrasound examination. Now with the
      application of high-frequency ultrasonography, the detection rate of scrotal
      calculi is gradually increasing. This article summarizes the etiology,
      pathogenesis, clinical manifestations, diagnosis, and treatment of scrotal
      calculi.

PMID- 25577846
TI  - Infestations and fungal diseases.

PMID- 25577847
TI  - Scabies.
AB  - Scabies infestation in humans is a complex interplay between mite, host, and host
      environment. New techniques for diagnosis, treatment, and eradication are
      constantly in flux due to varying presentations of scabetic eruptions, a dearth
      of especially sensitive and specific measures for diagnosis, resistances to
      pharmacologic therapy, and disparate regional resources. This review will provide
      an update on the clinical variations, detection methods, and management options.

PMID- 25577848
TI  - Dermatoses associated with mites other than Sarcoptes.
AB  - Mites are arthropods of the subclass Acari (Acarina). Although Sarcoptes is the
      mite most commonly recognized as a cause of human skin disease in the United
      States, numerous other mite-associated dermatoses have been described, and merit
      familiarity on the part of physicians treating skin disease. This review
      discusses several non-scabies mites and their associated diseases, including
      Demodex, chiggers, Cheyletiella, bird mites, grain itch, oak leaf itch, grocer's
      itch, tropical rat mite, snake mite, and Psoroptes.

PMID- 25577849
TI  - Lice.
AB  - Pediculosis (capitis, corporis, and pubis) share well-known features: worldwide
      prevalence (involving millions of people annually); parasites inducing skin
      lesions directly, and indirectly as a result of itching and hypersensitivity to
      parasites; and treatment based on good entomological knowledge of the parasite
      and practical considerations (ie, most available treatments do not act on eggs
      and should be repeated, depending on the life cycle of the parasites).
      Infestations are spread most commonly by close contacts. Social stigma and
      persistent misconceptions complicate the implementation of appropriate management
      strategies. Head and pubic lice infestations are diagnosed by the visualization
      of insects or viable nits (eggs). Primary treatments are topical pediculicides
      (permethrin or malathion), used twice, but emergence of resistance against
      pediculicides has created the need of alternative treatments including topical or
      oral ivermectin. Pubic lice are treated the same as head lice, but this finding
      should prompt evaluation for other sexually transmitted diseases. Body lice
      infestation should be suspected when symptoms of generalized itching occur in
      persons who do not change or wash their clothing or bedding regularly; lice may
      be found in the seams of their clothing.Topically administered permethrin may
      help to eradicate body lice, but personal hygiene measures are essential for
      successful treatment. Environmental treatment is also necessary for the
      eradication of the infestation. Health care personnel who come into contact with
      this population need to be well informed of the facts in order to disseminate
      accurate information for diagnosis and management.

PMID- 25577850
TI  - Bed bugs.
AB  - The term bed bug is applied to 2 species of genus Cimex: lectularius describes
      the common or temperate bed bug, and hemipterus its tropical cousin. Cimex
      lectularius is aptly named; its genus and species derive from the Latin words for
      bug and bed, respectively. Though the tiny pest is receiving increased public
      attention and scrutiny, the bed bug is hardly a new problem.

PMID- 25577851
TI  - Spiders in dermatology.
AB  - Spider bites represent an unusual and potentially over-represented clinical
      diagnosis. Despite a common fear of spiders, known as arachnophobia, current
      knowledge suggests that only a small number of families within the order Araneae
      are medically relevant. Moreover, most cutaneous spider reactions, including both
      evenomations and physical trauma, produce mild, local symptoms which may be
      managed with supportive care alone. The differential diagnosis for spider bites
      may be broad, especially if the offending arachnid is not seen or found. We
      describe a series of spiders relevant to the dermatologist in the United States.

PMID- 25577852
TI  - Helminths: a clinical review and update.
AB  - This article provides a focused update and clinical review on select helminth
      infections. The goal is to report atypical clinical presentations and newer
      management recommendations. The results and recommendations should be interpreted
      with the understanding that future studies may alter what is presented.

PMID- 25577853
TI  - Tropical dermatology: cutaneous larva migrans, gnathostomiasis, cutaneous
      amebiasis and trombiculiasis.
AB  - In today's world, many people can travel easily and quickly around the globe.
      Most travel travel-related illnesses include fever, diarrhea, and skin disease,
      which are relatively uncommon in returning travelers. We review four of the most
      common emerging infestations and skin infections in the Americas, which are
      important to the clinical dermatologist, focusing on the clinical presentation
      and treatment of cutaneous larva migrans, gnathostomiasis, cutaneous amebiasis,
      and trombiculiasis.

PMID- 25577854
TI  - What's new in the treatment and diagnosis of dermatophytosis?
AB  - Superficial fungal infections of the skin and nails are common in humans and can
      cause patients substantial discomfort. Additionally, patients may find the
      physical appearance of these infections to be distressing. Although the
      infectious fungi have evolved to parasitize humans, the ability to treat and
      diagnose fungal infections has been slower to progress. Nevertheless, there are
      promising new advancements in the treatment and diagnosis of dermatophyte
      infection. New topical and light-based treatments for dermatophytoses are
      available, and the first meta-analysis of topical antifungal treatments has been
      performed. Diagnostic improvements are forthcoming for dermatophytoses with the
      advent of molecular techniques for rapid identification and speciation of
      dermatophytes.

PMID- 25577855
TI  - Coccidioidomycosis.
AB  - Coccidioidomycosis is a common, environmentally acquired, pulmonary fungal
      infection in arid and semi-arid regions of the West, especially Arizona and
      California. The infection is frequently associated with striking cutaneous
      manifestations. Reactive, immunologically mediated eruptions include erythema
      nodosum, a generalized exanthem, Sweet syndrome, and reactive granulomatous
      dermatitis. Less commonly, the skin can harbor the actual organisms as a result
      of dissemination from the lungs. Dermatologists may play a key role in the
      recognition of coccidioidomycosis

PMID- 25577857
TI  - Are you a future nursing journal editor?

PMID- 25577856
TI  - Subcutaneous (deep) fungal infections.
AB  - Fungal infection is a common clinical problem in dermatology. While most cases in
      practice are superficial infections, invasive subcutaneous mycoses are important
      to recognize and treat, as these conditions often have significant morbidity and
      mortality. Deep fungi demonstrate species-specific syndromes and may be
      identified by clinical and histological features in addition to serological
      evaluation and culture. Identification of the common innoculation subcutaneous
      mycoses, as well as those associated with pulmonary primary infection and
      dissemination to the skin is important, as treatments vary by organism and
      clinical setting. This overview will help to identify the key dermatological
      presentations of subcutaneous fungal infection, and the clues they give to cause.

PMID- 25577858
TI  - Mentoring faculty for success.

PMID- 25577859
TI  - The status quo of situation-specific theories.
AB  - The purpose of this article is to explore the status quo of situation-specific
      theories through an integrated literature review on situation-specific theories
      that have been published since 1999. The literature was searched through multiple
      databases including PubMed, CINAHL, and PsycINFO and analyzed in terms of purpose
      of theorizing, types of theorizing, sources of theorizing, and linkages to
      research or practice. Four themes reflecting the current status of situation
      specific theories were extracted: (a) explicitly claimed and not explicitly
      claimed situation-specific theories; (b) multiple philosophical bases; (c) unique
      theorizing process; and (d) providing clear directions for nursing interventions
      but rarely evaluated. Nurses need to continuously make their efforts to develop
      theoretical bases that could closely link theory, research, and practice in
      nursing and that could adequately serve new nursing needs and challenges.

PMID- 25577860
TI  - Seeing the whole person: feasibility of using the Omaha System to describe
      strengths of older adults with chronic illness.
AB  - A promising strategy for enhancing care and self-management of chronic illness is
      an integrative, whole-person approach that recognizes and values well-being.
      Assessment tools are needed that will enable health care professionals to
      perceive patients as whole persons, with strengths as well as problems. The
      purpose of this study was to examine the feasibility of using a standardized
      terminology (the Omaha System) to describe strengths of older adults with chronic
      illness. The Omaha System assessment currently consists of identifying
      signs/symptoms for 42 health concepts. Researchers mapped self-reported strengths
      phrases to Omaha System concepts using existing narratives of 32 older adults
      with 12-15 comorbid conditions. Results demonstrated the feasibility of
      describing strengths of patients with chronic illness. Exploratory analysis
      showed that there were 0-9 strengths per patient, with unique strengths profiles
      for 30 of 32 patients. Given that older adults with multiple chronic illnesses
      also have strengths that can be classified and quantified using the Omaha System,
      there is potential to use the Omaha System as a whole-person assessment tool that
      enables perception of both problems and strengths. Further research is needed to
      enhance the Omaha System to formally represent strengths-based as well as a
      problem-focused perspectives.

PMID- 25577861
TI  - Finding myself: a theory on the maturation of spirituality and its influence on
      behavior during late adolescence.
AB  - This study employed a grounded theory research design to develop a theoretical
      model focused on the maturation of spirituality and its influence on behavior
      during late adolescence. Quantitative research studies have linked spirituality
      with decreased health-risk behaviors and increased health-promotion behaviors
      during late adolescence. Qualitative, theoretical data is proposed to discover
      the underlying reasons this relationship exists and increase the ability to apply
      this knowledge to practice. Twenty-one adolescents, age 16-21 years, were e-mail
      interviewed and transcripts analyzed using a conceptual lens of Blumer's symbolic
      interactionism. From this analysis, a theoretical model emerged with the core
      concept, finding myself that represents 5 core process concepts. Implications of
      this study illustrate that late adolescents are aware of their personal spiritual
      maturation as well as its influence on behavior. In addition, a distinction
      between the generic concept of spirituality, personal spirituality, and religion
      emerged.

PMID- 25577862
TI  - Nonpharmacological techniques to reduce pain in preterm infants who receive heel
      lance procedure: a randomized controlled trial.
AB  - INTRODUCTION: The heel-lance (HL) method for blood collection from the newborn is
      controversial for the pain it causes. This is the first randomized controlled
      trial on the management and reduction of pain using the music of Wolfgang Amadeus
      Mozart ("Sonata K. 448") in premature infants hospitalized in a neonatal
      intensive care unit (NICU). This study has compared nonpharmacological techniques
      with standard procedure for reducing pain during HL procedure. METHODS: Thirty
      five premature infants were enrolled, each for 3 HL procedures, of which each was
      randomized to 1 of the 3 study arms. Arms were then compared in terms of the
      Premature Infant Pain Profile (PIPP) changes by analysis of variance (ANOVA).
      RESULTS: One hundred five HL procedures were available for analysis (35 standard
      procedure, 35 music, 35 glucose). Median baseline PIPP was 3, and median PIPP
      after the HL procedure was 5. PIPP scale change was +3 in the control arm, +1 in
      the glucose arm, +2 in the music arm (p = .008). DISCUSSION: Both glucose and
      music were safe and effective in limiting pain increase when compared to standard
      procedure in HL procedures in preterm infants.

PMID- 25577863
TI  - [Research advance in the drug target prediction based on chemoinformatics].
AB  - The emerging of network pharmacology and polypharmacology forces the scientists
      to recognize and explore new mechanisms of existing drugs. The drug target
      prediction can play a key significance on the elucidation of the molecular
      mechanism of drugs and drug reposition. In this paper, we systematically review
      the existing approaches to the prediction of biological targets of small molecule
      based on chemoinformatics, including ligand-based prediction, receptor-based
      prediction and data mining-based prediction. We also depict the strength of these
      methods as well as their applications, and put forward their developing
      direction.

PMID- 25577864
TI  - [Potential targets for anti-liver fibrosis].
AB  - Liver fibrosis is a pathological process of the excessive accumulation of
      extracellular matrix, especially collagen al (I) in liver. Ultimately, hepatic
      fibrosis leads to cirrhosis or hepatic failure. Liver fibrosis and early
      cirrhosis can be reversed, thus control of the development of liver fibrosis is
      very important for preventive treatment of cirrhosis and hepatic failure. This is
      a review of potential targets for anti-hepatic fibrosis based on plenty of
      publications, including TGF-beta1 and integrin alpha(v) and so on, aimed at
      providing novel therapeutic targets in liver fibrosis.

PMID- 25577865
TI  - [The research progress of metals correlated to Alzheimer's disease].
AB  - Alzheimer's disease (AD) is a kind of neurodegenerative diseases, the most common
      cause of dementia. Although AD has been studied more than, 100 years and the
      Abeta and tau theory are most widely accepted among the theories achieved, yet it
      is not really clear what the mechanism related to AD works up to now. However, it
      is certain that AD is a kind of diseases resulting from multi-causes. Except for
      causes correlated with heredity, aging and life habits, environmental role is
      worth taking into consideration as well. Some metals, such as copper, aluminum,
      zinc and iron et al, can also have close relationship with AD. Now, we make an
      overview on the correlative researches in the field.

PMID- 25577866
TI  - [A review of the expression and activity of drug metabolism enzymes in tumorous
      cells].
AB  - Tumorous cells are characterized by distinctive metabolic reprogramming and
      living conditions. Understanding drug metabolizing features in tumor cells will
      not only favor the estimation of metabolic rate, elimination half life and the
      assessment of potency, but also facilitate the optimal design of anti-tumor
      drugs/prodrugs. This article reviewed the expression and activity features of
      major drug metabolizing enzymes (DMEs) in solid tumorous tissues, such as liver,
      intestine, breast and lung, and the difference from the correspondingly normal
      tissues, exemplified by the metabolic properties of some classic antitumor-agents
      in tumorous tissues. In combination with the data retrieved in vitro tumor cell
      lines, we discussed the similarities and differences of DMEs expression and
      function between tumor tissues (in vivo) and tumor cells (in vitro), and proposed
      the possible factors that cause the differences.

PMID- 25577867
TI  - [Pharmaphylogeny vs. pharmacophylogenomics: molecular phylogeny, evolution and
      drug discovery].
AB  - With the surge of high-throughput sequencing technology, it is becoming popular
      to perform the phylogenetic study based on genomic data. A bundle of new terms is
      emerging, such as phylogenomics, pharmacophylogenomics and phylotranscriptomics,
      which are somewhat overlapping with pharmaphylogeny. Phylogenomics is the
      crossing of evolutionary biology and genomics, in which genome data are utilized
      for evolutionary reconstructions. Pharmaphylogeny, advocated by Prof. Pei-gen
      Xiao since 1980s, focuses on the phylogenetic relationship of medicinal plants
      and is thus nurtured by molecular phylogeny, chemotaxonomy and bioactivity
      studies. Phylogenomics can be integrated into the flow chart of drug discovery
      and development, and extend the field of pharmaphylogeny at the omic level, thus
      the concept of pharmacophylogenomics could be redefined. This review gives a
      brief analysis of the association and the distinguished feature of the
      pharmaphylogeny related terms, in the context of plant-based drug discovery and
      sustainable utilization of pharmaceutical resource.

PMID- 25577868
TI  - [Establishment of an ultrasonographic method for evaluating the hepatic lipid
      accumulation in mice].
AB  - To investigate the semi-quantitative method for evaluating lipid accumulation in
      livers, male C57BL/6J mice (CON), HFD mice characterized with the mild fatty
      liver induced by high-fat diet, and KKAy mice charactered with the moderately
      severe fatty liver induced by high-caloric diet were used. The lipid accumulation
      was estimated by the histological examination (HE staining) and the content of
      hepatic triglyceride, separately. Echo-intensity of two selected regions along
      the ultrasound transmission direction was recorded using a small animal
      ultrasonographic system, and the echo-intensity attenuation coefficient was
      calculated. Correlation between the echo-intensity attenuation coefficient and
      the content of hepatic triglyceride was analyzed by the Spearman's rank
      correlation analysis. The results showed that the lipid accumulation in livers
      increased significantly in both HFD and KKAy mice compared with CON mice and it
      was more serious in KKAy mice than that in HFD mice. The values of echo-intensity
      attenuation coefficient were also increased in sequence according to group. These
      values were positively associated with the content of hepatic triglyceride (r =
      0.744, P < 0.01). In conclusion, the echo-intensity attenuation coefficient is a
      simple, impersonal, and non-invasive method for evaluating the hepatic lipid
      accumulation. It can be used to research the process and the treatment of fatty
      liver diseases in mice.

PMID- 25577869
TI  - [Effect of astaxanthin on preeclampsia rat model].
AB  - The effect of astaxanthin on N(Omega)-nitro-L-arginine methyl ester (L-NAME)
      induced preeclampsia disease rats was investigated. Thirty pregnant Sprague
      Dawley rats were randomly divided into three groups (n = 10): blank group, L-NAME
      group and astaxanthin group. From day 5 to 20, astaxanthin group rats were
      treated with astaxanthin (25 mg x kg(-1) x d(-1) x bw(-1)) from pregnancy (day
      5). To establish the preeclamptic rat model, L-NAME group and astaxanthin group
      rats were injected with L-NAME (125 mg x kg(-1) x d(-1) x bw(-1)) from days 10-20
      of pregnancy. The blood pressure and urine protein were recorded. Serum of each
      group was collected and malondialdehyde (MDA), superoxide dismutase (SOD) and
      nitric oxide synthase (NOS) activities were analyzed. Pathological changes were
      observed with HE stain. The expression of NF-kappaB (nuclear factor kappa B),
      ROCK II (Rho-associated protein kinase II), HO-1 (heme oxygenase-1) and Caspase 3
      were analyzed with immunohistochemistry. L-NAME induced typical preeclampsia
      symptoms, such as the increased blood pressure, urinary protein, the content of
      MDA, etc. Astaxanthin significantly reduced the blood pressure (P < 0.01), the
      content of MDA (P < 0.05), and increased the activity of SOD (P < 0.05) of
      preeclampsia rats. The urinary protein, NO, and NOS were also decreased. HE stain
      revealed that after treated with astaxanthin, the thickness of basilal membrane
      was improved and the content of trophoblast cells and spiral arteries was
      reduced. Immunohistochemistry results revealed that the expressions of NF-kappaB,
      ROCK II and Caspase 3 in placenta tissue were effectively decreased, and HO-1 was
      increased. Results indicated that astaxanthin can improve the preeclampsia
      symptoms by effectively reducing the oxidative stress and inflammatory damages of
      preeclampsia. It revealed that astaxanthin may be benefit for prevention and
      treatment of preeclampsia disease.

PMID- 25577870
TI  - [The estrogen-like protective effect of ginsenoside Rb3 on oxidative stress and
      dysfunction of endothelial cells induced by oxidized low-density lipoprotein].
AB  - Ginsenoside Rb3 (GRb3) is one of the main components in plasma of Panax
      quinquefolius Saponin of stem and leaf (PQS), which can be into human plasma.
      Previous studies have found PQS has estrogen-like vascular protective effects. In
      the present study, we investigated the estrogen-like protective effect of GRb3 on
      oxidative stress and dysfunction of endothelial cells induced by oxidized low
      density lipoprotein. The activities of SOD, NOS and the contents of MDA in the
      cell lysate were examined by enzyme method or spectrophotometry. The NO and ET-1
      concentrations in the cell culture supernatant were measured by ELISA method. The
      iNOS and eNOS mRNA expression were measured by real time RT-PCR, while the
      phosphorylation levels of Akt was measured by Western blotting. The results
      showed that GRb3 could enhance the activity of SOD, reduce the content of MDA,
      increase the level of NOS, NO, ET-1 and iNOS mRNA expression while decrease the
      eNOS mRNA expression and the phosphorylation level of Akt. These effects were
      blocked by estrogen receptor antagonist ICI182780. GRb3 can play a role in
      protecting vascular endothelial cells by estrogen receptors, the protective
      mechanism is similar to 17-beta estrodiol.

PMID- 25577871
TI  - [Tissue distribution of PEGylated puerarin in acute myocardial ischemia mode
      rats].
AB  - The aim of this study is to explore the tissue distribution of PEGylated puerarin
      in acute myocardial ischemia model rats. Healthy male SD rats were randomly
      divided into two groups (30 each). Both were given PEGylated puerarin at a dose
      of 488 mg x kg(-1). After 5 min of medication, one group was normal rats, another
      group with acute myocardial ischemia was established by peritoneal injection of
      50 mg x kg(-1) isoprenaline. After administration, the animals were executed at
      30, 60, 90, 120, 150 and 180 min, then heart, liver, spleen, lung, kidney were
      extracted. The content of puerarin in organ tissue was determined by HPLC. The
      results showed that the AUC of tissue distribution of PEGylated puerarin in
      normal rats was liver > kidney > heart ~ spleen > lung > brain. While the AUC of
      tissue distribution of PEGylated puerarin in acute myocardial ischemia model rats
      was liver ~ heart > kidney > lung ~ spleen > brain. AUC(heart) of PEGylated
      puerarin in acute myocardial ischemia model rats was 1.7 times than that of the
      normal rats, and there was significant difference (P < 0.05). Thus, PEGylated
      puerarin had a good heart-targeting property in early myocardial infarction area,
      drugs could accumulate in the ischemic myocardium. It provided important
      information for further study and clinic use of PEGylated puerarin.

PMID- 25577872
TI  - [Pharmacokinetics and pharmacodynamics of huangqin tang in febrile rats].
AB  - The pharmacodynamic (PD) and pharmacokinetic (PK) properties of Huangqin Tang
      (HQT) were investigated in yeast-induced febrile rats. Blood sample and rectal
      temperature data of the rats were collected at different times after single oral
      administration of HQT at 20 g x kg(-1). The plasma concentrations of
      paeoniflorin, baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic
      acid and glycyrrhetinic acid were quantified by a sensitive liquid chromatography
      tandem mass spectrometric (LC-MS) method. The blood concentrations of PGE2, 1L
      1beta and TNF-alpha were detected by radioimmunoassay (RIA). All pharmacokinetic
      parameters were processed by non-compartmental analysis using WinNonlin software.
      The potential relationship between the mean concentration of eight constituents
      and the antifebrile efficacy was investigated by calculating Pearson correlation
      coefficients. It was found that HQT had significant antifebrile efficacy in yeast
      induced febrile rats, but had no effect to normal rats. The antifebrile effect of
      HQT can be attributed to the inhibition of PGE2, 1L-1beta and TNF-alpha. The
      constituents (baicalin, wogonoside, baicalein, wogonin, oroxylin A, glycyrrhizic
      acid and glycyrrhetinic acid) in febrile rats had delayed absorption and
      elimination, a longer residence time in the body, and higher C(max) and AUC than
      those in normal rats. Febrile condition could affect the pharmacokinetic
      behaviour of HQT in vivo; the flavonoids with the same backbone showed the
      similar fate in the body; baicalein and wogonin had a strong positive correlation
      (R > 0.66, P <= 0.02) with the antifebrile efficacy determined. Together, these
      constituents demonstrated different pharmacokinetic properties in the febrile
      body.

PMID- 25577873
TI  - [Population pharmacokinetics and pharmacodynamics of clopidogrel in patients with
      acute coronary syndrome].
AB  - This study established a population pharmacokinetics-pharmacodynamics model of
      clopidogrel in patients with acute coronary syndrome. Fifty-nine patients were
      enrolled. The plasma concentration of clopidogrel active metabolite and
      vasodilator stimulated phosphoprotein platelet reactivity index (VASP-PRI) were
      selected as the pharmacokinetics index and the pharmacodynamics index,
      respectively. The covariates including demographic characteristics, laboratory
      indexes, combined medication, complications and genetic polymorphisms of related
      enzymes were screened for their influence on the pharmacokinetic and
      pharmacodynamics parameters. Population pharmacokinetic and pharmacodynamics data
      analysis was performed using NONMEM software. The general linear model and the
      indirectly effect model-turnover model for pharmacokinetic and pharmacodynamic
      analysis were selected as the basic model, respectively. The population typical
      values of K12, CL/F, V/F, EC50, K(in), and E(max) were 0.259 h(-1), 179 L x h(
      1), 632 L, 1.57 ng x mL(-1), 4.29 and 0.664, respectively. CYP2C19 was the
      covariate in the final pharmacokinetic model, and the model was to design a prior
      dosage regimen.

PMID- 25577874
TI  - Two new sulfated sesquiterpenoids from Petasites tricholobus.
AB  - Two new sulfated sesquiterpenoids, megastigman-7-ene-3, 5, 6, 9-tetrol-3-O-beta-D
      6'-sulfonated-glucopyranoside (1) and 3-O-beta-D-6'-sulfonated-glucopyranosyl-6
      (3-oxo-2-butenylidenyl)-1, 1, 5-trimethylcyclohexan-5-ol (2), along with one
      known sesquitepenoid compound icariside B1 (3) were isolated from the whole herb
      of Petasites tricholobus Franch. Their structures were identified by their
      chemical and spectroscopic characters. All obtained compounds were tested for
      their cytotoxicity against four cancer cell lines.

PMID- 25577875
TI  - [Renchangianin E: a new dibenzocyclooctadiene lignan from Kadsura renchangiana].
AB  - A new dibenzocyclooctadiene lignan, renchangianin E (1) was isolated from the
      stems of Kadsura renchangiana. Its structure and stereochemistry were elucidated
      by spectroscopic methods, including 2D-NMR techniques.

PMID- 25577876
TI  - [Synthesis and antifatigue activities of new benzamide derivatives].
AB  - To explore novel antifatigue agents targeting with AMPA receptor, 10 compounds
      were synthesized and their structures were confirmed by 1H NMR, ESI-MS and
      elemental analysis. 1-BCP was treated as the leading compound. The antifatigue
      activities were evaluated by weight-loaded forced swimming test, and the AMPA
      receptor binding affinities were tested with radioligand receptor binding assays.
      The results unveiled that 5b appeared to possess potent antifatigue activities
      and high affinity with AMPA receptor, which deserved further studies.

PMID- 25577877
TI  - [Comparison of the chemical composition between fresh and dried venenum bufonis
      by UPLC-Orbitrap MS].
AB  - To identify the active components in Bufo melanostictus Schneider and clarify the
      difference between fresh and dried Venenum Bufonis, a UPLC-Orbitrap MS method has
      been established. The separation was performed with gradient elution of
      acetonitrile and water (with 0.1% formic acid) as mobile phase. By comparing
      their retention time and high resolution mass data of Venenum Bufonis extracts,
      39 effective components were primarily identified by MS/MS analysis in positive
      ion mode. Twenty-six of them were bufadienolides. There were significant
      differences in the main composition between fresh and dried Venenum Bufonis.
      There are fewer bufadienolides in fresh toad venom.

PMID- 25577878
TI  - [Pharmacodynamic differences between hangmaidong and chuanmaidong based on
      metabonomics].
AB  - To evaluate the differences of Ophiopogonjaponicus from different cultivations,
      the metabolomics based method was conducted to compare the effects of Hangmaidong
      and Chuanmaidong (Chinese name) on plasma endogenous metabolites of normal rats.
      Data were collected by ultra performance liquid chromatography quadrupole time of
      flight mass spectrometry (UPLC-Q-TOF/MS), and were analyzed by multivariate
      statistical method, such as Principal Component Analysis and Orthogonal Signal
      Correction Partial Least Square Discriminant Analysis. Results revealed that the
      plasma metabolites profiling of low and middle dose group of Chuanmaidong were
      similar to the control group, but different from the high dose group obviously.
      Meanwhile the high, middle and low dose groups of Hangmaidong were different from
      control group notably, and the difference is dose dependent.
      Lysophosphatidylcholines, the possible endogenous metabolites which contribute to
      the classification most significantly, are closely related to cardiovascular
      system diseases. Compared with the group of Chuanmaidong, Hangmaidong has greater
      impact on the plasma metabolic profiling of normal rats. Hangmaidong and
      Chuanmaidong showed significant differences pharmacodynamically.

PMID- 25577879
TI  - [Preparation and characterization of tumor targeted CdTe quantum dots modified
      with functional polymer].
AB  - N-acetyl-L-cysteine (NAC) capped quantum dots (QDs) were synthesized by a
      hydrothermal method and coated with 2-amino-2-deoxy-D-glucose (DG), polyethylene
      glycol (PEG), and 9-D-arginine (9R). The optical properties, morphology and
      structure of 9R/DG-coated CdTe QDs were characterized by ultraviolet-visible
      spectrometry, fluorescence spectrum, Fourier transform infrared (FTIR), proton
      nuclear magnetic resonance (1H NMR), liquid chromatography-mass spectrometer (LC
      MS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and
      transmission electron micrographs (TEM). Furthermore, the biocompatibility, tumor
      targeted ability and transmembrane action of 9R/DG-coated CdTe QDs were studied.
      Results indicated that 9R/DG-coated CdTe QDs was constructed successfully by
      ligand exchange. The 9R/DG-coated CdTe QDs with the size of 8-10 nm had good
      dispersity and the absorbance and fluorescence peaks of CdTe QDs after
      modification were red shifted from 480 nm to 510 nm and 627 nm to 659 nm,
      respectively. In addition, the CdTe QDs modified by PEG, DG and 9R displayed good
      biocompatibility, high targeted ability to the cancer cells with glucose
      transporter type 1 (GLUT1) receptor high expression and obvious transmembrane
      ability.

PMID- 25577880
TI  - [DNA barcoding research and its application on medicinal plants of Bletilla H. G.
      Reichenbach].
AB  - To identify adulterants from medicinal plants of Bletilla H. G. Reichenbach, the
      suitable candidate DNA barcoding of Bletilla was evaluated. In this study, the
      internal transcribed spacer (ITS) of nuclear ribosomal DNA, the LFY homologous
      gene intron 2 and chloroplast ycfl gene were amplified and sequenced from forty
      one samples. The intra-specific and inter-specific divergences of Bletilla were
      calculated, and the identification efficiency was assessed using Barcoding Gap,
      NJ tree by K2P distance and BLAST1 method. The result showed the intra-specific
      divergence of nrDNA ITS and ycJfl (0.022-0.106 and 0.017-0.106) were obviously
      higher than the inter-specific divergence (0-0.012 and 0-0.015), and four species
      of Bletilla were also accurately distinguished in NJ trees. Whereas, there was no
      Barcoding Gap on LFY homologous gene intron 2, thus it cannot effectively
      identify species of Bletilla. Using NJ tree of nrDNA ITS and ycfl gene, powdery
      medicine and the adulterants of Bletilla were successfully unidentified. In
      conclusion, nrDNA ITS and ycfl can be used as a potential DNA barcoding to
      identify the medicinal plants in Bletilla and its adulterants. There were only
      three basic differences on nrDNA ITS between "Jujing baiji" and Bletilla striata
      of Lu'an in Anhui province, and two basic differences in ycfl. Based on
      morphological and molecular data, "Jujing baiji" could be recognized as the
      species of Bletilla striata.

PMID- 25577881
TI  - [Determination of intrinsic alliin dissolution rates with fiber-optic sensing
      process analysis].
AB  - The apparatus for intrinsic dissolution test recorded in United States
      Pharmacopeia (USP) integrating with fiber-optic drug dissolution test system
      (FODT) were used to real-time monitor intrinsic dissolution processes of alliin
      in four media which were water, solution of HCl with pH 1.2, buffer solution of
      acetate with pH 4.5, and buffer solution of phosphate with pH 6.8. The intrinsic
      dissolution rate (IDR) and the similarity factor (f2) of two intrinsic
      dissolution curves with two apparatuses were calculated. The IDR values of alliin
      with rotating disk system were 28.1.3, 33.55, 28.38 and 30.95 mg x cm(-2) x min(
      1) in four media, respectively. And the IDR values of alliin with stationary disk
      system were 44.16, 47.07, 45.11 and 51.34 mg x cm(-2) x min(-1), respectively.
      The similarity factors were 56.42, 50.75, 40.30 and 40.64, respectively. The
      results showed that the intrinsic alliin dissolution rates were much greater than
      1 mg x cm(-2) x min(-1). It inferred that alliin dissolution would not be the
      rate limiting step to absorption.

PMID- 25577882
TI  - What is a compounding pharmacist?

PMID- 25577883
TI  - Robotized compounding of oncology drugs in a hospital pharmacy.
AB  - In 2005, the Pharmacy Department of the University Hospital of Ancona began
      collaboration with the engineers of the Loccioni group in order to realize a
      fully automated system for the preparation of cytostatic drugs, which could be
      safe for both healthcare workers and patients. At present, the cytotoxic
      laboratory of Ancona is equipped with two robots and one Class II biological
      safety cabinet. The introduction of the robots in the cytotoxic laboratory has
      increased both efficiency and safety of the working process. The drug-preparation
      process begins when the pharmacist confirms the medical prescription (exact
      posology, modalities of reconstitution), and starts the preparation cycle. The
      sterility of the preparations is monthly tested in collaboration to the local
      microbiology laboratory. All preparations' results were germ-free even after
      storage at room temperature for two weeks. The dose accuracy is verified by
      visual and gravimetric independent systems. Drug concentration errors exceeding
      the limit of 10% fixed by the Italian Pharmacopeia were found only in 1.1% of the
      preparations. The average dose error was 0.8% (standard deviation 1.7%).

PMID- 25577884
TI  - To compound or not to compound: a veterinary transdermal discussion.
AB  - Administering chronic medications to feline patients without the daily battle of
      oral and injectable medications is the holy grail of veterinary pharmacotherapy.
      For some medications, the transdermal route may be the solution. However, there
      are many considerations for determining if a medication will be safe for the
      patient and caregiver as well as effective when administered transdermally. A
      comprehensive checklist to assess the appropriateness of transdermal therapy is
      provided.

PMID- 25577885
TI  - Autologous serum eye drops for severe dry eye syndrome in a patient with chronic
      graft-versus-host disease: a case report.
AB  - We present the case of a 49-year-old woman with severe dry eye syndrome caused by
      chronic graft-versus-host disease that developed after an allogeneic
      hematopoietic transplant to treat acute myelogenous leukemia. After the use of
      commercially manufactured products for the treatment of dry eye failed to relieve
      her photosensitivity, blurred. vision, and severe bilateral ocular pain, she
      benefitted significantly from therapy with compounded autologous serum eye drops.
      Comments from that patient are included in this report, as are a formulation for
      the preparation of autologous eye drops and suggestions for their safe and
      effective use.

PMID- 25577886
TI  - Final guidance for pharmacy compounding of human drug products under Section
      503A.

PMID- 25577887
TI  - Health care in Belarus in the 19th and 20th centuries.
AB  - Belarus became a Soviet Socialist Republic in the USSR in 1921. Belarus is now an
      independent country between Poland and Lithuania and Russia. The pharmacy sector
      of Belarus improved in fits and starts from 1921 to the present but serious
      quantitative and qualitative problems were evident until the 21st century. A
      number of factors caused this situation. The Soviet Republic of Belarus started
      with handicaps. The area, comprised of several provinces of western Russia, had
      no pharmaceutical factories during the imperial period and, while pharmacies were
      of high quality in the cities all over the Russian Empire--including Minsk, which
      became the capital of Belarus--pharmacies were sparse and primitive in rural
      areas and Belarus was basically rural. Belarus was devastated by wars--World War
      I, the Russian-Polish war of 1920-21, and of course, by World War II. The
      Bolshevik policy of nationalizing private pharmacies adversely affected
      dispensing between 1918 and 1921. Dispensing improved during the New Economic
      Policy of 1921 to 1927 with re-introduction of private enterprise and the
      establishment of BelMedTorg and the Mogilev Experimental Station of Medicinal
      Plants. The number of pharmacies and medical facilities increased during the
      1930s and again after World War II. However, utopian plans to provide free or low
      cost medicines to all citizens never came to fruition. Inadequate amounts of
      state-of the-art and even basic medicines persisted through the 1990s. The number
      of pharmacists also was inadequate and their education and training was on a low
      level. Because of shortages, citizens of Belarus often self-medicated with
      medicinal plants. The transition to a market economy in the 1990s made medicines
      expensive for citizens but opened the door to greater interaction with Western
      pharmaceutical practices and physical improvements in pharmacies and
      pharmaceutical production.

PMID- 25577888
TI  - Compounding practices in a Portuguese community pharmacy.
AB  - All Portuguese community pharmacies have a compounding laboratory and minimum
      equipment for the preparation of nonsterile (traditional) compounded medicines,
      but a few community pharmacies specialize in compounding. At Farmacia Lordelo,
      the most frequently dispensed compounded medicines are oral liquids for
      pediatrics and multi-drug, semi-solid preparations for dermatology patients. The
      majority of the compounded medicines is prepared in accordance with the national
      galenic formulary and standardized monographs, in order to guarantee the quality
      and safety of the compounded medicines dispensed.

PMID- 25577890
TI  - Basics of compounding: tips and hints, Part 5: Facilities and equipment.

PMID- 25577889
TI  - Certification of sterile equipment and facilities: what pharmacists need to know.
AB  - Although it is common knowledge that all sterile compounding pharmacies must have
      their equipment and facilities certified and calibrated every six months, it is
      not as clear what is expected of pharmacists. There is currently a disconnect
      between the certification companies and the pharmacists. As pharmacists, we look
      to the certification companies as the experts and rely upon them accordingly. The
      certification companies look upon the pharmacy to know which testing is required.
      It is the role of the pharmacist to know which tests are necessary and how they
      are to be interpreted correctly. The end goal of certification testing is to
      prove that the standards listed in United States Pharmacopeia Chapter <797> are
      met. Testing requirements can vary from state to state. A few of the most
      commonly required sterile certification and calibration tests will be discussed
      in this article.

PMID- 25577891
TI  - Tips on dealing with a healthcare practitioner's no-rep policy.

PMID- 25577892
TI  - Stability and in vitro toxicity of an infliximab eye drop formulation.
AB  - The purpose of this study was to develop a novel 10-mg/mL infliximab eye drop, to
      characterize its physical and biological stability under recommended storage
      conditions, and to assess the formulation's toxicity to ocular surface epithelium
      in vitro. Infliximab (10 mg/mL) was reconstituted using equal volumes of sterile
      water and 1% carboxymethylcellulose artificial tears. Aliquots were stored in
      either a 4 degrees C refrigerator or -20 degrees C freezer for up to 45 days.
      Physical stability was assessed through monitoring the solution's appearance, pH,
      ultraviolet-visible-near infrared absorbance and scattering, as well as protein
      gel electrophoresis. Biological stability was assayed through binding to tumor
      necrosis factor-alpha using an enzyme-linked immunosorbent assay. In vitro
      cytotoxicity to human corneal-limbal epithelial cells was examined following a 4
      hour exposure to the study drug. Refrigerated and frozen infliximab eye drops
      remained clear and colorless for the duration of study. The formulation's pH
      (7.0) was comparable to that of the artificial tear vehicle alone. Low levels of
      ultraviolet-visible-near infrared light absorbance and scattering established the
      lack of protein precipitate after refrigeration or freezing. Protein gel
      electrophoresis performed under reducing conditions revealed the presence of two
      main protein bands of approximately 50 kDa and 25 kDa, representing
      immunoglobulin G heavy and light chains. The migration pattern of the proteins
      did not change under the different storage conditions and between day 10 and 45
      after formulation. Infliximab binding to tumor necrosis factor-alpha remained
      stable for up to 45 days, with conservation of 101% and 102% of its initial
      binding activity when refrigerated or frozen, respectively. In vitro human
      corneal-limbal epithelial cultures showed no increase in cytotoxicity with
      infliximab treatment when compared to vehicle and culture media controls (P >
      0.05). Infliximab can be formulated as an eye drop and remains stable when stored
      in accordance with current regulations regarding compounded eye drops. The
      demonstrated physical and biological stability as well as in vitro innocuity of
      this infliximab eye drop formulation may facilitate future clinical investigation
      targeting tumor necrosis factor-alpha as a modulator of various ocular surface
      diseases.

PMID- 25577893
TI  - Physicochemical and microbiological stabilities of hydrocortisone in InOrpha
      suspending agent studied under various conditions.
AB  - Hydrocortisone is principally used as replacement therapy in adrenocortical
      deficiency states. In pediatric practice, posology ranges from 10 to 20 mg/m2 per
      day, divided in three doses, for the purpose of mimicking the nycthemeral cycle.
      Hydrocortisone is marketed in France in tablet form that contains 10 mg of the
      active ingredient. This galenic formulation is not suitable for pediatric use,
      and often requires a grinding operation or a dose fractionation to facilitate
      administration. To overcome this difficulty, the objective of this study was to
      develop and evaluate the physicochemical and microbiological stabilities of
      hydrocortisone in a sugar-free, alcohol-free, and paraben-free InOrpha suspending
      agent. The studied samples were formulated into a 2-mg/mL suspension and stored
      in glass bottles at two temperature conditions, between 2 degrees C to 8 degrees
      C and at room temperature). Two series of twelve samples were tested for
      physicochemical stability using high-performance liquid chromatography as well as
      for a microbiological status for 28 days (daily opening of the bottles from day 0
      of compounding) and for 56 days (first opening at day 28 from compounding and
      daily opening for 28 consecutive days). The high-performance liquid
      chromatography method developed is linear, accurate, precise, and robust. On the
      other hand, a forced degradation study has demonstrated the selectivity and
      specificity of the method validated as stability indicating. In both storage
      conditions, high-performance liquid chromatography analysis showed that tested
      samples had concentrations ranging within 90% to 110% of the initial
      concentration for 28 consecutive days upon daily bottle opening and, for a
      maximum of 42 days with a first opening at day 28 from the compounding time.
      Microbiological status remained stable throughout the course of the study. Based
      on the data collected, the study led to the development of a new galenic
      formulation of hydrocortisone suitable for pediatric use which can be safely
      stored under refrigerated conditions or at room temperature for a maximum of 42
      consecutive days.

PMID- 25577894
TI  - Stability of tranexamic acid in 0.9% sodium chloride, stored in type 1 glass
      vials and ethylene/propylene copolymer plastic containers.
AB  - Tranexamic acid has recently been demonstrated to decrease all-cause mortality
      and deaths due to hemorrhage in trauma patients. The optimal administration of
      tranexamic acid is within one hour of injury, but not more than three hours from
      the time of injury. To aid with timely administration, a premixed solution of 1
      gram tranexamic acid and 0.9% sodium chloride was proposed to be stocked as a
      medication in both the aeromedical transport helicopters and Emergency Department
      at Mayo Clinic Hospital--Rochester Saint Marys Campus. Since no published
      stability data exists for tranexamic acid diluted with 0.9% sodium chloride, this
      study was undertaken to determine the stability of tranexamic acid diluted with
      0.9% sodium chloride while being stored in two types of containers. Stability was
      determined through the use of a stability-indicating high-performance liquid
      reverse phase chromatography assay, pH, and visual tests. Tranexamic acid
      solutions of 1 gram in 0.9% sodium chloride 65 mL were studied at predetermined
      intervals for 90 days in ethylene/propylene copolymer plastic containers,
      protected from light, and at both controlled room and refrigerated temperatures.
      Tranexamic acid solutions of 1 gram in 0.9% sodium chloride 50 mL were studied at
      predetermined intervals for 180 days in clear Type 1 borosilicate glass vials
      sealed with intact elastomeric, Flourotec-coated stoppers, stored protected from
      light at controlled room temperature. Solutions stored in the ethylene/propylene
      copolymer plastic containers at both storage temperatures maintained at least 98%
      of initial potency throughout the 90-day study period. Solutions stored in glass
      vials at controlled room temperature maintained at least 92% of initial potency
      throughout the 180-day study period. Visual and pH tests revealed stable, clear,
      colorless, and particulate-free solutions throughout the respective study
      periods.

PMID- 25577895
TI  - The effect of IL-2, IL-12 and IL15 on the function of natural killer cells in
      children suffering from type 1 diabetes mellitus.
AB  - INTRODUCTION: The immunologic reaction of pancreatic islets destruction leads to
      the occurrence of type 1 diabetes mellitus (T1D). The autoreactive lymphocytes
      play the pivotal role in this process although mechanisms regulating the
      lymphocyte migration and infiltration of Langerhans islets have not been fully
      understood yet. The in vitro studies showed natural killer (NK) cells potency to
      initiate pancreatic islets cell lyses. Many authors postulate that NK cells may
      be involved in this reaction. AIM OF THE STUDY: The aim of the study was to
      evaluate the effect of IL-2, IL-12 and IL-15 stimulation on peripheral blood NK
      cells in children suffering from type 1 diabetes mellitus in comparison to
      healthy controls. MATERIAL AND METHODS: Fifteen children with type 1 diabetes and
      10 healthy adults were examined. NK cells were isolated by the magnetic cell
      separation system (MACS). For activation, NK cells were cultured with IL-2, IL-12
      and IL-15 for 24 hours. The production of IFN-gamma and IL-10 by NK cells was
      measured using commercial ELISA kits. FACS analysis of cell surface antigens-
      CD16, CD56, NKG2D and CD137 was performed using LSR II flow cytometer. RESULTS:
      In children with T1D the IFN-gamma median concentration in supernatant obtained
      from NK cells culture was 16.831 ng/ml (inter quartile range 5.566-25.509) and
      did not statistically differ from median IFN-gamma concentration in the control
      group--14.810 ng/ml (7.022-18.785), p = 0.76. In contrast, the IL-10 median
      concentration was statistically higher in T1D patients 7.87 pg/ml (1.32-11.37)
      than in healthy participants--1.41 pg/ml (1.05-4.81), p = 0.01. The median (inter
      quartile range) percentage of NK NKG2D(+) was found in 0.42% (0.28-0.76) cells of
      TID patients versus 0.72% (0.53-1.08) in the controls (p = 0.05). There was no
      difference between -T1D group and the control group in regard to NK cells
      expressing CD137 - 6.58% (3.38-12.4) versus 6.85% (2.94-10.8); p = 0.8.
      CONCLUSIONS: The observed activity of NK cells after in vitro stimulation by IL2,
      IL-12 and IL15 in children suffering from type 1 diabetes mellitus indicates the
      tendency for supporting the inhibition of autoimmunological reaction by increased
      IL10 synthesis and increased number of NK cells with surface NKG2D receptors.

PMID- 25577896
TI  - An analysis of the IGF-I receptor coding sequence in the genome of children with
      growth disorders.
AB  - INTRODUCTION: Growth disorders in children are multifactor, complex processes
      with often unknown etiology. The insulin-like growth factor-I (IGF-I) is one of
      the proteins participating in the transfer of growth signals, which are
      responsible in certain cases for the etiology of a growth disorder. AIM OF THE
      STUDY: The aim of the study was an analysis of the coding sequence of the
      extracellular and intracellular domains of IGF-IR responsible for ligand binding
      (IGF-I) and kinase activity in the DNA of children with growth disorders, who
      have normal or slightly decreased levels of plasma IGF-I. MATERIAL AND METHODS:
      DNA isolated from the peripheral blood of 50 short-statured children was used as
      study material. DNA fragments of IGF-IR obtained as a result of PCR amplification
      were analyzed using single stranded conformation polymorphism (SSCP) and
      sequencing. RESULTS: We did not observe any changes in the IGF-IR sequences, thus
      it can be excluded as a factor responsible for growth disorders. CONCLUSIONS: IGF
      I receptor sequence changes are not the cause of growth disorders in the study
      group of children. To find the cause of growth disorders in the study group other
      proteins from somatotropic axis and/or signaling pathways should be studied in
      the future.

PMID- 25577897
TI  - [Allergic diseases in children with type 1 diabetes].
AB  - INTRODUCTION: Th1/Th2 lymphocytes balance is connected with normal function of
      the immune system. Differentiation of lymphocytes Th towards Th1 is related to
      autoimmune diseases appearances and towards Th2 to appearance of atopic diseases.
      Aim of the study was to analyze the frequency of allergic diseases in children
      with type 1 diabetes mellitus. MATERIAL AND METHODS: A survey concerning the
      manifestation of allergic disorders was conducted in 92 patients (47 girls and 45
      boys aged from 2.8 to 18.75 years) with diagnosed diabetes type 1 and serous IgE
      Total levels were measured. RESULTS: The prevalence of allergic disorders (atopic
      rhinitis, conjunctivitis and asthma) among children with type 1 diabetes was more
      often than in the general population. Occurrence of the allergic disorders in the
      family is related to increasing frequency of AR, conjunctivitis and asthma. In
      children with type 1 diabetes and elevated serous IgE Total symptoms of allergy
      occur more often (69.20%) than in children with type 1 diabetes and normal level
      of serous IgE Total (58.46%). In the study group the frequency of appearance of
      other autoimmune diseases among children with elevated level of serous IgE Total
      (17.39%) was similar to the frequency among children with normal level of serous
      IgE Total (18.83%). CONCLUSIONS: In the study group of children with IDDM the
      prevalence of allergic disorders was more often than in the general population,.
      There were statistically significant correlations between eczema in infancy,
      positive family history of allergy and elevated serous total IgE with symptoms of
      allergic diseases. There was no correlation between elevated serous total IgE and
      prevalence of other autoimmunological diseases.

PMID- 25577898
TI  - Bad eating habits as the main cause of obesity among children.
AB  - Obesity is undoubtedly one of the biggest medical problems of the 21st century.
      Regrettably, the problem affects more and more children and adolescents. 10% of
      world's school-aged children have an excess body weight and a quarter of these
      children are obese. In Europe every fifth school-aged child suffers from an
      excess body weight. The prevalence of overweight and obesity among Polish
      adolescents is about 14%. An excess body weight can be the consequence of genetic
      factors, endocrine disorders or certain drugs. However, "simple obesity" is the
      most common, consequence of providing too much energy from food products in
      comparison to energy expenditure (caloric excess). Today's lifestyle promotes the
      development of obesity. The lack of physical activity, sedentary lifestyle and
      energy-rich diet are the main causes of an excess body fat accumulation. Because
      of improper eating behaviours children consume an excess amount of energy; and
      their diet is deficient in elements necessary for proper development. The
      examples of such bad eating habits are: snacking highly processed and calorie
      rich foods between meals eating in front of the TV screen, skipping breakfasts,
      drinking sugar-sweetened beverages, "eating out" frequently and "emotional
      eating". Bad eating behaviours are crucial factors for the development of
      obesity. Eating habits are usually formed in early childhood and parents play a
      very important role in their development.

PMID- 25577899
TI  - Multihormonal hypopituitarism, hypothyroidism and hypoparathyroidism in a 17
      years-old girl with Diamond-Blackfan anemia and secondary hemochromatosis.
AB  - Congenital hypoplastic anemia (Diamond-Blakcfan syndrom) is a genetically
      determined disorder which is manifested in early childhood with selective
      deficiency of erythrocyte line in bone marrow. Severe anemia usually appears in
      the first six months of life. Survival depends on blood transfusions, which in
      consequence lead to hemochromatosis. The most common complications of
      transfusional hemochromatosis are hepatic cirrhosis, hypopituitarism,
      hypogonadism, diabetes mellitus, other endocrinopathies, and cardiomyopathy. We
      present the case of 17 years old girl with congenital hypoplastic anemia and
      multihormonal insufficiency due to secondary hemochromatosis.

PMID- 25577900
TI  - Ganglioneuroma in a patient with Turner syndrome.
AB  - INTRODUCTION: Ganglioneuroma is a benign neuroblastal tumor that derives from
      immature cells of the sympathetic nerve system. It is a very rare disease and
      affects newborns and infants more often than adolescents and adults. The benign
      tumors are relatively difficult to diagnose since they usually are asymptomatic.
      We present a case of unusual coincidence of an ganglioneuroma and Turner syndrome
      (TS). CASE REPORT: An 11.5-year-old TS patient was admitted into the hospital
      with good general condition. She was 7 months into growth hormone (GH) therapy.
      The reason for the admission was to carry out control tests. The patient had not
      complains or abnormalities on physical examination. On the ultrasound examination
      of the abdomen in the right adrenal area an adrenal tumor was identified. The
      ultrasound examination of the abdomen performed 13 months earlier did not show
      any abnormalities. Computed tomography of adrenal glands confirmed right adrenal
      tumor. The hormonal function of the adrenal gland was normal. The treatment with
      GH was terminated and the patient was urgently referred to surgical management.
      The right adrenal gland tumor together with a part of diaphragm was removed. On
      histopathological examination ganglioneuroma maturum was diagnosed. On the
      control MIBG examination physiological gaining of tracer in the left adrenal and
      in the rest tissue in the area of the right adrenal was found. Trepanobiopsy did
      not confirm neoplastic changes. CONCLUSIONS: There is a necessity of careful
      monitoring of TS patients also in face of the possibility of disclosure
      previously not stated neoplasm after starting GH therapy. It is impossible to
      rule out that GH therapy promote growth of existing neoplasm.

PMID- 25577901
TI  - Optimal audiovisual integration in people with one eye.
AB  - People with one eye show altered sensory processing. Such changes might reflect a
      central reweighting of sensory information that might impact on how multisensory
      cues are integrated. We assessed whether people who lost an eye early in life
      differ from controls with respect to audiovisual integration. In order to
      quantify the relative weightings assigned to each sensory system, participants
      were asked to spatially localize audiovisual events that have been previously
      shown to be optimally combined and perceptually fused from the point of view of
      location in a normal population, where the auditory and visual components were
      spatially disparate. There was no difference in the variability of localizing
      unimodal visual and auditory targets by people with one eye compared to controls.
      People with one eye did however, demonstrate slower reaction times to localize
      visual stimuli compared to auditory stimuli and were slower than binocular and
      eye-patched control groups. When localizing bimodal targets, the weightings
      assigned to each sensory modality in both people with one eye and controls were
      predictable from their unimodal performance, in accordance with Maximum
      Likelihood Estimation and the time it took all three groups to localize the
      bimodal targets was faster than for vision alone. Regardless of demonstrating a
      longer response time to visual stimuli, people with one eye appear to integrate
      the auditory and visual components of multisensory events optimally when
      determining spatial location.

PMID- 25577902
TI  - Investigation of the effects of color on judgments of sweetness using a taste
      adaptation method.
AB  - It has been reported that color can affect the judgment of taste. For example, a
      dark red color enhances the subjective intensity of sweetness. However, the
      underlying mechanisms of the effect of color on taste have not been fully
      investigated; in particular, it remains unclear whether the effect is based on
      cognitive/decisional or perceptual processes. Here, we investigated the effect of
      color on sweetness judgments using a taste adaptation method. A sweet solution
      whose color was subjectively congruent with sweetness was judged as sweeter than
      an uncolored sweet solution both before and after adaptation to an uncolored
      sweet solution. In contrast, subjective judgment of sweetness for uncolored sweet
      solutions did not differ between the conditions following adaptation to a colored
      sweet solution and following adaptation to an uncolored one. Color affected
      sweetness judgment when the target solution was colored, but the colored sweet
      solution did not modulate the magnitude of taste adaptation. Therefore, it is
      concluded that the effect of color on the judgment of taste would occur mainly in
      cognitive/decisional domains.

PMID- 25577903
TI  - Red hot: the crossmodal effect of color intensity on perceived piquancy.
AB  - Color cues can influence the experience of flavor, both by influencing
      identification and perceived intensity of foods. Previous research has largely
      focused on the crossmodal influence of vision upon taste or olfactory cues. It is
      plausible that color cues could also affect perceived trigeminal sensation; these
      studies demonstrate a crossmodal influence of color on piquancy. In our first two
      experiments, participants rated the spiciness of images of salsas that were
      adjusted to vary in color and intensity. We found that red was associated with
      significantly higher ratings of expected spice than blue, and that darker reds
      were expected to be spicier than lighter reds. In our third experiment,
      participants tasted and then rated the spiciness of each of four salsas (with two
      levels of color and of piquancy) when sighted and when blindfolded. Spiciness
      ratings were unaffected by differing colors when the salsa was mild, but when the
      piquancy was increased, a lack of increase in color corresponded to a depressed
      spiciness. These results can be explained using a model of assimilation and
      contrast. Taken together, our findings show that in our US sample, there is a
      crossmodal correspondence between visual and trigeminal senses that can influence
      perception of spiciness.

PMID- 25577905
TI  - Modality dependent cross-modal functional reorganization following congenital
      visual deprivation within occipital areas: a meta-analysis of tactile and
      auditory studies.
AB  - Cross-modal responses in occipital areas appear to be essential for sensory
      processing in visually deprived subjects. However, it is yet unclear whether this
      functional recruitment might be dependent on the sensory channel conveying the
      information. In order to characterize brain areas showing task-independent, but
      sensory specific, cross-modal responses in blind individuals, we pooled together
      distinct brain functional studies in a single based meta-analysis according only
      to the modality conveying experimental stimuli (auditory or tactile). Our
      approach revealed a specific functional cortical segregation according to the
      sensory modality conveying the non-visual information, irrespectively from the
      cognitive features of the tasks. In particular, dorsal and posterior subregions
      of occipital and superior parietal cortex showed a higher cross-modal recruitment
      across tactile tasks in blind as compared to sighted individuals. On the other
      hand, auditory stimuli activated more medial and ventral clusters within early
      visual areas, the lingual and inferior temporal cortex. These findings suggest a
      modality-specific functional modification of cross-modal responses within
      different portions of the occipital cortex of blind individuals. Cross-modal
      recruitment can thus be specifically influenced by the intrinsic features of
      sensory information.

PMID- 25577904
TI  - Synaesthesia or vivid imagery? A single case fMRI study of visually induced
      olfactory perception.
AB  - The most common form of synaesthesia is grapheme-colour synaesthesia. However,
      rarer forms of synaesthesia also exist, such as word-gustatory and olfactory
      gustatory synaesthesia, whereby a word or smell will induce a specific. In this
      study we describe a single individual (LJ) who experiences a concurrent olfactory
      stimulus when presented with congruent visual images. For some visual stimuli, he
      perceives a strong and automatic olfactory percept, which has existed throughout
      his life. In this study, we explore whether his experiences are a new form of
      synaesthesia or simply vivid imagery. Unlike other forms of synaesthesia, the
      concurrent odour is congruent to the visual inducer. For example, a photograph of
      dress shoes will elicit the smell of leather. We presented LJ and several control
      participants with 75 images of everyday objects. Their task was to indicate the
      strength of any perceived odours induced by the visual images. LJ rated several
      of the images as inducing a concurrent odour, while controls did not have any
      such percept. Images that LJ reported as inducing the strongest odours were used,
      along with colour-matched control images, in the context of an fMRI experiment.
      Participants were given a one-back task to maintain attention. A block-design
      odour localizer was presented to localize the piriform cortex (primary olfactory
      cortex). We found an increased BOLD response in the piriform cortex for the odour
      inducing images compared to the control images in LJ. There was no difference in
      BOLD response between these two stimulus types in the control participants. A
      subsequent olfactory imagery task did not elicit enhanced activity in the
      piriform cortex in LJ, suggesting his perceptual experiences may not be based on
      olfactory imagery.

PMID- 25577906
TI  - [Progress on treatment for elbow joint injuries].

PMID- 25577907
TI  - [Case-control study on therapeutic effects of different fixation methods for the
      treatment of olecranon fracture].
AB  - OBJECTIVE: To evaluate the clinical effects by comparing three different fixation
      methods: tension band, hollow lag screw and anatomical plate. METHODS: From
      January 2010 to January 2012, 82 patients with olecranon fractures who underwent
      surgical treatments were followed-up. All the patients were divided into three
      groups: tension band fixation group (group A), hollow lag screw fixation group
      (group B), anatomical plate fixation (group C). In group A, there were 35
      patients, including 19 males and 16 females, ranging in age from 32 to 49 years
      old, with an average of (43.6 +/- 8.7) years old, and the patients were treated
      with tension band fixation. According to Colton classification, there were 5
      cases of type I, 3 cases of type II A,19 cases of type II B, and 8 cases of type
      II C in group A. Among 20 patients in group B, there were 13 males and 7 females,
      ranging in age from 27 to 50 years old, with an average of (41.5 +/- 9.3) years
      old. The patients in group B were treated with hollow lag screw fixation.
      According to Colton classification, there were 4 cases of type I, 4 cases of type
      II A, and 12 cases of type II B in group B. In group C, there were 27 patients
      totally, including 15 males and 12 females, ranging in age from 30 to 55 years
      old, with an average of (38.2 +/- 6.2) years old. The patients in group C were
      treated with anatomical plate fixation. According to Colton classification, there
      were 4 cases of type II B, 13 cases of type II C, and 10 cases of type II D in
      group C. The Fracture healing time, complications and functional recovery were
      retrospectively observed and recorded. RESULTS: All the patients were followed
      up, and the duration ranged from 8 to 24 months, with an average of 15 months.
      The average healing time of patients in group C was the longest among three
      groups. The flexion-extension and rotation activities of elbow joint in group B
      and C were better than that in group C. According to Broberg & Morrey score
      system, the therapeutic effects of patients in group A and B were better than
      that of group C. In group C, 2 patients had incision infections, 6 patients
      complained of foreign body sensation, 1 patient got a delayed fracture healing,
      and 1 patient had the heterotopic ossification. There were no occurrences of
      incision infections in group A and B; internal fixation loosening occurred in 3
      patients in group A and 2 patients in group B; delayed fracture healing occurred
      in 2 patients in group A and 2 patients in group B; and skin bursa formation
      occurred in 6 patients in group A and 1 patient in group B. CONCLUSION: All the
      three ways are effective methods for the treatment of olecranon fractures.
      Fixation methods should be selected depending on the type of fracture.

PMID- 25577908
TI  - [Treatment of terrible triad of elbow with open reduction and internal fixation
      through anteromedial approach combined with lateral approach].
AB  - OBJECTIVE: To study therapeutic effects of anteromedial approach combined with
      lateral approach for the treatment of terrible triad of elbow. METHODS: From
      November 2009 to March 2013,17 patients with terrible triad of elbow were treated
      through anteromedial approach combined with lateral approach. There were 11 males
      and 6 females, with an average age of 36.6 years old, ranging from 22 to 68 years
      old. Ten patients had fractures in the left side and 7 patients had fractures in
      the right side. All of which were close fractures. Coronoid process fractures
      were reduced and treated with internal fixation through the anteromedial
      approach, and the incision was located between radiocarpus and cubitalis grailis.
      In order to expose the lateral collateral ligament joint capsule and capitulum
      radii, Kocher approach was used with the incision between triceps brachii muscle
      and brachioradialis muscle along condylus lateralis humeri, down to posterior
      side between anconeus muscle and extensor carpi ulnaris muscle. Then capitulum
      radii fractures were treated with internal fixation using miniature plates and
      screws, and lateral collateral ligament complexes were repaired using fasciole
      rivets. Mayo elbow performance score (MEPS) was used to evaluate clinical effects
      at the latest follow-up. RESULTS: All the patients were followed up, and the
      duration ranged from 13 to 24 months,with a mean of 12.4 months. At the latest
      follow-up, the average flexion angle of all patients was (134.0 +/- 8.8) degrees;
      the average extension angle was (6.4 +/- 2.3) degrees. According to the Mayo
      criteria system, the average total score was 91.8 +/- 7.9, including pain score
      42.4 +/- 5.9, range of motion score 17.6 +/- 2.6, joint stability score 9.7 +/-
      1.2, and functional score 22.1 +/- 2.5; 13 patients got an excellent result and 4
      good. Two patients had transient ulnar nerve palsy, and 1 patient had heterotopic
      ossification. There were no complications such as infection, nonunion, elbow
      residual instability, dislocation and elbow stiffness. CONCLUSION: The operation
      through anteromedial approach combined with lateral approach for the treatment of
      terrible triad of elbow has advantages of providing both bone and soft-tissue
      stability simultaneously, allowing early exercise and improving early functional
      recovery.

PMID- 25577909
TI  - [Case-control study on comprehensive traditional Chinese medicine therapy for
      preventing postsurgery stiffness after operation for terrible triad of the
      elbow].
AB  - OBJECTIVE: To study therapeutic effects of comprehensive traditional Chinese
      medicine therapy for preventing postsurgery stiffness after operation for
      terrible triad of the elbow. METHODS: From December 2008 to December 2013,32
      patients with elbow triad were randomly divided into two groups: therapy group
      and control group. There were 17 patients in control group including 12 males and
      5 females with a mean age of (41.0 +/- 7.1) years old. The patients in control
      group were received the past procedure therapy. There were 15 patients in therapy
      group, including 10 males and 5 females with a mean age of (41.3 +/- 7.6) years
      old. The patients in therapy group were received comprehensive traditional
      Chinese medicine therapy, including passive exercise training at early stage (0
      to 2 weeks after operation), transition from passive to active exercise training
      at middle stage (3 to 4 weeks after operation), and active exercise training at
      late stage (5 to 12 weeks after operation). Other treatment methods, such as
      orally taking or externally use of Chinese herbal medicine, manipulation and
      physiotherapy, were used at all stages. The Mayo Elbow Performance Score, patient
      satisfaction and complications were evaluated and analyzed. RESULTS: All the
      patients were followed up, and the mean duration was 7.5 months. There were no
      complications such as internal fixation loosing, obvious displacement fracture
      and heterotopic ossification occurred. The Mayo score and patient satisfaction in
      therapy group were higher than those in control group (t = 12.78, P = 0.00; chi2
      = 8.719, P = 0.003). Seven patients needed reoperation in control group, compared
      with 1 patient in therapy group (chi2 = 4.626, P = 0.032). CONCLUSION: The
      comprehensive traditional Chinese medicine therapy is effective to prevent
      postoperative stiffness after operation for terrible triad of the elbow by using
      different methods at different stages, which is worthy of spread and application.

PMID- 25577911
TI  - [Case-control study on local injection of autoallergic platelet rich plasma or
      whole blood for the treatment of tennis elbow].
AB  - OBJECTIVE: To compare therapeutic effects of local injection with autoallergic
      platelet rich plasma (PRP) or autoallergic whole blood (AWB) for the treatment of
      chronic tennis elbow. METHODS: From January 2011 to January 2014, 40 patients
      with chronic tennis elbow were divided into 2 groups, 20 cases in each group: PRP
      group and AWB group. There were 20 patients in PRP group treated with local
      injection of autoallergic platelet rich plasma, including 5 males and 15 females,
      with an average age of (47.50 +/- 9.86) years old; and the average course of
      disease was (4.67 +/- 3.27) months. Among the 20 patients in AWB group treated
      with local injection of autoallergic whole blood, 3 patients were male and 17
      patients were female, with an average age of (46.50 +/- 9.96) years old;and the
      average course of disease was (4.53 +/- 2.27) months. The elbow joint was fixed
      with elastic stockings after injection. All the patients were guided to do
      strengthening and extension exercises during the follow-up period. Visual analog
      scale (VAS), Mayo scores for elbow and pressure pain threshold (PPT) were used to
      evaluate clinical effects after injection immediately and 4,8 weeks after
      treatment. Results:All the patients were followed up,there were no infections and
      swelling occurred. The VAS, Mayo and PPT scores of patients in PRP group were
      improved from pre-therapy 7.22 +/- 1.32, 56.71 +/- 10.90 and 17.47 +/- 4.62 to
      2.73 +/- 1.00, 91.59 +/- 6.95 and 21.35 +/- 4.80 respectively 8 weeks after
      treatment. The VAS, Mayo and PPT scores of patients in AWB group were improved
      from pre-therapy 7.16 +/-1.27, 54.72 +/- 8.36 and 17.06 +/- 4.83 to 3.81 +/-
      1.36, 82.06 +/- 7.89 and 20.12 +/- 4.97 respectively 8 weeks after treatment. All
      the pain and functional variables including VAS, PPT, and Mayo scores were
      improved significantly in both groups 4 weeks after injection. On the 4th week
      after injection, there was no statistically significant difference in PPT between
      two groups; while the VAS and Mayo score of AWB group were lower than those of
      PRP group. On the 8th week after injection, the VAS of AWB group was higher than
      that of PRP group; but the Mayo and PPT scores of AWB group were lower than those
      of PRP group. CONCLUSION: PRP and AWB injections are both effective to treat
      chronic lateral epicondylitis. Compared with AWB injection, PRP injection may be
      more effective in releasing pain and improving function for a longer time.

PMID- 25577910
TI  - [Case-control study on the occurrence of cubitus varus deformity after humeral
      supracondylar fractures treated with plaster fixation in pronated or supinated
      position in children].
AB  - OBJECTIVE: To retrospectively compare the occurrence of cubitus varus deformity
      after humeral supracondylar fractures treated with manipulative reduction and
      plaster fixation in pronated or supinated position in children, and to guide
      clinical treatment. METHODS: From June 2009 to December 2011, the medical data of
      64 children with humeral supracondylar fractures treated by manipulative
      reduction and plaster fixation were reviewed. All the patients were divided into
      two groups: group A and group B. The 30 patients in group A were treated with
      manipulative reduction and plaster fixation in pronation, including 18 males and
      12 females, with a mean age of (7.5 +/- 3.5) years old. The 34 patients in group
      B were treated with manipulative reduction and plaster fixation in supination,
      including 23 males and 11 females, with a mean age of (7.0 +/- 2.6) years old.
      The occurrence rates of cubitus varus and decreases of carrying angle were
      compared between two groups before and after treatment. RESULTS: There were 13
      patients in group A and 16 patients in group B having cubitus varus,which had no
      statistical difference (chi2 = 0.089, P = 0.765). The decrease of carrying angle
      were (8 +/- 4) degrees in group A and (9 +/- 5) degrees in group B, which had no
      statistical difference (t = 0.584, P = 0.564). Within group A, the occurrence
      rate of cubitus varus and the decrease of carrying angle between the radial
      deviation and the ulnar deviation had statistically significant difference (chi2
      = 6.160, P = 0.013; t = - 2.409, P = 0.035). Within group B, the occurrence rate
      of cubitus varus and the decrease of carrying angle between the radial deviation
      and the ulnar deviation had statistically significant difference (chi2 = 5.120, P
      = 0.024; t = -2.250, P = 0.041). The elbow function Flynn evaluation score had no
      significant difference between two groups (P = -0.822). CONCLUSION: The
      occurrence rate of cybutys varys and the decrease of carrying angle have no
      obvious difference in children with humeral supracondylar fractures treated with
      fixation in pronated or supinated position. However, when treating with
      pediatrics humerus supracondylar fractures with ulnar deviation, the fixation in
      pronation is more helpful for reducing the occurrence rate of elbow varus and
      decrease of carrying angle. When treating with the pediatrics humerus
      supracondylar fractures with radial deviation, fixation in supination is helpful
      for reducing the occurrence rate of elbow varus and decrease of carrying angle.

PMID- 25577912
TI  - [X-ray characteristics of posterolateral rotatory instability of the elbow caused
      by ligament injury].
AB  - OBJECTIVE: To study the role of lateral collateral ligament complex on the
      posterolateral rotatory instability and the relationship between the
      radiocapitellar ratio (RCR) and the injury of lateral collateral ligament complex
      on X-ray images. METHODS: Twenty elbow joints from fresh-frozen adult cadavers
      were used to make osteo-ligamentous elbow specimens. The specimens were fixed
      with a self-made device to maintain posterolateral rotatory instability of the
      elbow joint. All the specimens were divided into two groups: group A and group B.
      Surgical procedures were carried out as follows in the lateral structures of
      group A: A1, intact specimen; A2, transection of radial ulnar collateral ligament
      firstly; A3, transection of annular ligament secondly; A4, final transection of
      the radial collateral ligament. The procedures in group B were carried out as
      follows: B1, intact specimen; B2, transection of the radial collateral ligament
      firstly; B3, transection of the annular ligament secondly; B4, final transection
      of the radial ulnar collateral ligament. Lateral X-ray films of elbow joint were
      taken, and the radiocapitellar ratio (RCR) was measured by using PACS. All
      analysis was performed with SPSS 17.0 software. RESULTS: Group A: the increases
      in RCR had statistical differences among A1, A2, A3, and A4 groups. Group B: the
      increases in RCR had no statistical differences among B1, B2 and B3 groups; but
      the increase in RCR in group B4 was more than that in B1, B2 and B3 groups.
      CONCLUSION: The radial ulnar collateral ligament is a key structure to maintain
      posterolateral rotatory stability;the radial collateral ligament and the annular
      ligament are the secondary important structures. There are 4 grades of the
      posterolateral rotatory instability of the elbow, according to the X-ray imaging
      classification.

PMID- 25577913
TI  - [Effects of body mass index on postoperative outcome in patients with
      osteoarthritis after total knee arthroplasty].
AB  - OBJECTIVE: To study effects of body mass index (BMI) on postoperative outcome in
      patients with osteoarthritis after total knee arthroplasty (TKA). METHODS: The
      data of 148 patients with osteoarthritis who underwent TKA from June 2006 to May
      2009 in our hospital and had complete follow-up data were analyzed
      restrospectively, including 29 males and 119 females, ranging in age from 39 to
      89 years old, with an average age of 71.2 years old. According to BMI
      classification standard, all the patients were divided into 4 groups: non-obese
      group (BMI <= 25.0 kg/m2), had 38 patients (45 knees), including 9 males and 29
      females, with a mean age of (70.0 +/- 8.2) years old; overweight group (BMI 25.1
      to 27.0 kg/m2), had 40 patients (48 knees), including 10 males and 30 females,
      with a mean age of (72.6 +/- 7.4) years old; obesity group (BMI 27.1 to 30.0 kg/
      m2), had 30 patients (43 knees), including 7 males and 30 females, with a mean
      age of (70.4 +/- 6.0) years old; morbidly obesity group (BMI > 30.0 kg/m2), 33
      patients (39 knees), including 3 males and 30 females, with a mean age of (71.7
      +/- 6.4) years old. The index such as Knee Society Score (KSS), anterior knee
      pain and patella cartilage damage during surgery were recorded before surgery and
      at the time of follow-up. RESULTS: Postoperative KSS increased significantly
      compared to preoperative KSS, and the good rate reached to 97.1%. In the knee
      score, preoperative KSS and postoperative KSS had no significant differences
      among the four groups (preoperative P = -0.789; postoperative P = 0.133).
      However, compared with other groups, obesity group got the lowest preoperative
      function score (preoperative P = 0.036; postoperative P = 0.225). While the
      incidence of anterior knee pain was 9.7% (17/175), including 14 grade I and 3
      grade II. There were no significant differences in incidence of anterior knee
      pain among four groups (chi2 = 0.764, P = 0.862). The average BMI of the patients
      with anterior knee pain was (27.4 +/- 3.6) kg/m2, while the others' BMI was (27.5
      +/- 4.4) kg/m2. There was no statistically difference between two groups (t = 
      0.061, P = 0.951). There were no significant differences in patella cartilage
      damage among groups (chi2 = 7.070, P = 0.314). CONCLUSION: The KSS increases in
      all the different groups. Those patients get the benefit from TKA, and the obese
      patients can receive a similar postoperative outcome as the non-obese ones.

PMID- 25577914
TI  - [Case-control study on tibetan Baimai ointment (see symbol in text) for the
      treatment of wrist-dysfunction after distal radius fracture].
AB  - OBJECTIVE: To evaluate efficacy and safety of Baimai ointment (see symbol in
      text) in the treatment of wrist-dysfunction after distal radius fracture.
      METHODS: From April, 2011 to June, 2012, 43 patients with distal radius fracture
      were treated with plaster fixation. All the patients were divided into two group:
      test group and control group. Twenty-one patients in test group and 22 in control
      group, and the baseline was balance (P > 0.05). The 21 patients in test group
      were treated with Baimai ointment (see symbol in text), fomentation, functional
      exercises. The 22 patients in control group were treated with placebo,
      fomentation, functional exercises. Foment affected side wrist with wet towel in
      20 min before medication, with the temperature between 50 degrees C and 60
      degrees C. Smear drugs uniformly in range of 3 cm in the vicinity of palm stripes
      after drying (about 3 g) and take functional exercises for the activities of
      wrist and hand. Continuous follow the program per 8 hours once and follow-up for
      8 weeks. The Wrist's pain was assessed with VAS. The wrist's activities were
      measured with the protractor of orthopedic. Measure The grip strength was
      measured with dynamometer. The wrist's function were assessed with the table of
      Cooney. RESULTS: The test group had a significantly better results than those of
      control group in the extent of wrist's pain throughout the treatment (P < 0.001),
      and grip strength on the 28th day and the 56th day (P < 0.05), and Cooney
      functional assessment on the 56th day (P < 0.05). Wrist's activities had no
      significane difference throughout the 8 weeks (P > 0.05). There were no drug
      adverse reactions occurred. CONCLUSION: Tibetan Baimai ointment (see symbol in
      text) has the treatment of wrist-dysfunction after distal radius fracture for
      external use, which can reduce the extent of wrist's pain, promote grip strength
      recovery in the middle and late of process, promote wrist's function recovery
      latterly, and safety for external use.

PMID- 25577915
TI  - [Case-control study on open reduction and internal fixation for the treatment of
      humeral surgical neck fracture in aged patients].
AB  - OBJECTIVE: To summarize clinical experiences of open reduction and internal
      fixation for the treatment of humeral surgical neck fractures. METHODS: From May
      2008 to May 2013, 295 patients with humeral surgical neck fractures were divided
      into two groups: operation group and small splint group. In the operation group:
      there were 139 cases including 58 males and 81 females, treated with open
      reduction and locking plate fixation. The mean age of the patients was (70.3 +/-
      6.5) years old (ranged from 60 to 91 years old). The interval from injury to
      hospital ranged from 30 min to 15 days, with an average of (19.7 +/- 18.4) hours.
      In the small splint group: there were 156 cases including 75 males and 81
      females, treated with manipulative reduction and small splint external fixation.
      The mean age of the patients was (70.6 +/- 7.0) years old (ranged from 60 to 98
      years old). The interval from injury to hospital ranged from 1 hour to 15 days,
      with an average of (20.2 +/- 20.1) hours. The therapeutic effects were evaluated
      with shoulder pain, function, activity, anatomical indicators and total score
      according to Neer Score after treatment. RESULTS: All the patients were followed
      up, and the duration ranged from 5 to 20 months, with an average of 13.2 months.
      According to Neer Score, the total score of patients in the operation group was
      91.48 +/- 7.46; while in the small splint group, the score was 85.62 +/- 7.61;
      the score of patients in the operation group was higher than that of small splint
      group. CONCLUSION: Compared with small splint external fixation, the method of
      open reduction and internal fixation for the treatment of humeral surgical neck
      fracture in aged patients has several advantages such as reducing pain, improving
      functional recovery, getting a better anatomical position and better clinical
      effects.

PMID- 25577916
TI  - [Case-control study on therapeutic effects between posterior corpectomy,
      decompression and reconstruction and combined anterior-posterior surgery for the
      treatment of severe thoracolumbar fractures with incomplete paraplegia].
AB  - OBJECTIVE: To compare the clinical outcome between posterior corpectomy,
      decompression and reconstruction and combined anterior-posterior surgery in the
      treatment of severe thoracolumbar three column fractures with incomplete
      paraplegia, and to provide a basis for procedure selection. METHODS: Clinical and
      radiographic results of posterior corpectomy, decompression and reconstruction
      (group A) and combined anterior-posterior surgery (group B) in the treatment of
      severe thoracolumbar three column fractures with incomplete paraplegia were
      analyzed retrospectively from January 2008 to December 2012. In group A, there
      were 18 patients (10 males and 8 females). The fractures were located on T11 in 1
      case, T12 in 5 cases, L1 in 6 cases and L2 in 6 cases. In group B, there were 15
      patients (9 males and 6 females). The fractures were located on T1 in 1 case, T12
      in 5 cases, L1 in 5 cases and L2 in 4 cases. Neurological status was judged by
      Frankel grades. The X-ray and CT were used for evaluation of the restoration of
      anterior height of the fractured vertebral body, the correction of Cobbs angle,
      the decompression scope of spinal canal and the fusion. Complications related to
      operation were also considered. Results: The followup periods ranged from 12 to
      18 months (averaged 16 months). The mean operation time, perioperative bleeding,
      postoperative drainage were (200 +/- 43) min, (1100 +/- 344) ml, and (400 +/-
      112) ml respectively in group A; and (290 +/- 68) min, (1 500 +/- 489) ml, (900
      +/- 269) ml respectively in group B. There was statistically significant
      difference between groups A and B (P < 0.05). There were significant improvements
      in anterior height of fractured vertebral body and Cobbs angle after operation.
      But there was no significant difference between groups A and B (P > 0.05). In
      Frankel grades, all patients had one grade or more improvement postoperatively.
      There was no significant difference between two groups (P > 0.05). CONCLUSION:
      Treatment of thoracolumbar vertebra burst fractures with subtotal vertebrectomy,
      decompression and reconstruction of anterior column through posterior approach
      has a similar clinical result compared to the operation through combined anterior
      and posterior approach, but the posterior surgery decreased surgical trauma. It
      is an effective and safe surgical method.

PMID- 25577917
TI  - [Effect of different-intensity SEMFs on bone mineral density and histomorphometry
      in SD rats].
AB  - OBJECTIVE: To investigate the effects of different-intensity sinusoidal
      electromagnetic fields (SEMFs) on bone mineral density (BMD) and histomorphometry
      in SD rats. METHODS: Thirty female SD rats were randomly divided into three
      groups: group A (a control group), group B (0.1 mT group) and group C (0.6 mT
      group). The rats in group B and C were exposed to 50 Hz SEMFs 3 hours each day.
      However,the magnetic intensity was different between group B and group C:0.1 mT
      for group B and 0.6 mT for group C. After 8 weeks, all the animals were killed.
      Changes of BMD and histomorphometric properties were observed. RESULTS: Compared
      with group A, the BMD of whole body, femur and vertebrae of rats in group B
      increased significantly; the area percentage, number and width of bone trabeculae
      in vertebrae and femur of rats in group B were larger than those of group A; but
      the resolution of bone trabeculae of rats in group B was lower than that of group
      A. The trabecular number in group C rats were significantly decreased, compared
      with that in group A rats. The outcome of double fluorescence labeling in group B
      was found to be significantly different with that in group A. But the difference
      between rats in group A and C was not significant. CONCLUSION: This study
      demonstrates that 50 Hz 0.1 mT SEMFs can increase BMD, improve bone tissue
      microstructure and, promote bone formation.

PMID- 25577918
TI  - [Biomechanical characteristics analysis on discs with coflex fixation on the
      different segments of lower lumbar spine].
AB  - OBJECTIVE: To investigate the biomechanical differences between the surgery and
      adjacent segments of intervertebral discs in the lower lumbar spine, which were
      implanted with Coflex into the segments of L4, and L5S1, respectively. METHODS:
      Three finite-element models (the model of the intact lower lumbar sacrum,the L4.5
      and L5S1 segments implanted by Coflex) were developed, respectively. According to
      the spinal three-column loading theory, three models were forced by the
      physiological loads of upright standing, flexion and extension. The stress of the
      different areas of the disc annulus, the changes of intervertebral dorsal height
      and the degree of nucleus pulposus pressure were compared and analyzed. RESULTS:
      Coflex implanted into the L4.5 and L5S1 segments in compression and extension
      could both decrease the stress of the posterior area of intervertebral disc in
      the surgery segment, resist the changes of the intervertebral disc dorsal height
      and reduce the perssure of nucleus pulposus. Furthermore, the stress of the L5S1
      segment decreased when Coflex fixed the L4.5 segment in extension. However, when
      Coflex fixed the L5S1 segment, the stress of L4.5 segment had no significant
      changes. CONCLUSION: Coflex fixing the L4,5 and L5S1 segments can effectively
      decrease the stress of the surgery segmental discs, respectively. Furthermore,
      Coflex fixing L4,5 segment may play a biomechanical role in reducing the stress
      of L5S1 segment.

PMID- 25577919
TI  - [Arthroscopic surgery for the treatment of stiff elbow].
AB  - OBJECTIVE: To investigate the clinical results of arthroscopic surgery for the
      treatment of stiff elbow. METHODS: From October 2010 to December 2012, 27
      patients with stiff elbow were treated with arthroscopic debridement and joint
      capsular releasing. There were 18 males and 9 females, ranging in age from 24 to
      54 years old, with an average of 35.7 years old. Analgesia and rehabilitation
      were necessary after operation. Mayo criteria system was used to evaluate
      therapeutic effects. RESULTS: All the patients were followed up, and the duration
      ranged from 12 to 18 months, with a mean of 13.5 months. The mean maximum flexion
      angle of patients improved from preoperative (61.5 +/- 30.1) degrees to
      postoperative (102.5 +/- 20.1) degrees; and the mean maximum extension angle
      improved from preoperative (34.8 +/- 12.1) degrees to postoperative (16.3 +/-
      16.1) degrees; the average total range of motion improved from preoperative (34.2
      +/- 21.0) degrees to postoperative (84.9 +/- 9.2) degrees. According to the Mayo
      criteria system, the average score increased from preoperative 60.5 +/- 13.4 to
      postoperative 88.7 +/- 6.3; ten patients got an excellent result, 13 good and 4
      fair. CONCLUSION: Arthroscopic surgery to treat elbow stiffness has such
      advantages as minimal invasion, less blood loss, fast recovery, and clear
      visualization, which is effective to improve elbow joint functions with less
      complications.

PMID- 25577920
TI  - [Treatment of chronic large osteochondral fracture of femoral condyle with
      absorbable pins under arthroscopy].
AB  - OBJECTIVE: To evaluate clinical effects of fixation of chronic large
      osteochondral fragment in the weight-bearing area of femoral condyle using
      absorbable pins under arthroscopy. METHODS: From March 2007 to December 2011, 6
      patients with chronic large osteochondral fractures of femoral condyle were
      treated with absorbable pins under arthroscopy. Among the patients, there were 4
      males and 2 females, ranging in age from 14 to 48 years old, and the courses of
      disease ranged from 4 to 26 weeks. After injury, patients suffered from pain and
      swelling on the knee. The locations of injury were at the weight-bearing areas of
      femoral condyle. The depth of injury was degree IV according to ICRS
      classification. The area of injury was more than 4 cm2. The healing of
      osteochondral fracture was assessed by X-ray. Lysholm score, IKDC score and
      Tegner activity score were used to assess outcomes. RESULTS: The osteochondral
      fractures healed in all patients, and the cartilage became degenerative to some
      extent when performing a secondary exploration. The postoperative Lysholm score,
      IKDC score and Tegner activity score increased compared with those before
      operation. CONCLUSION: Using absorbable pins under arthroscopy for the treatment
      of chronic large osteochondral fracture of femoral condyle is effective to regain
      the flat structure of articular cartilage and promote the healing of
      osteochondral fracture.

PMID- 25577921
TI  - [Application of serial tightening of reserved suture threads in delayed incision
      closure].
AB  - OBJECTIVE: To study clinical outcomes of serial tightening of reserved suture
      threads in delayed incision closure. METHODS: From January 2005 to June 2013, 67
      patients with delayed incision closure were treated with serial tightening of
      reserved suture threads. There were 37 males and 30 females, with an average age
      of 40 years old (ranged from 12 to 75 years old). Among them, 36 patients
      suffering from leg or forearm double fractures had the incision difficult to
      those primarily due to high tension or mergency; 13 patients had open wound which
      lasted for more than routine time for debridement and closure; 9 patients had
      wound infection; 9 patients had decompression incisions owing to compartment
      syndrome. The No. 4 suture thread was used to sew up the incision, and the 4 to 6
      cm long thread was reserved at two ends of each thread. The reserved thread was
      tightened gradually from 2 to 4 days after operation according to conditions of
      swelling relieving. Finally, the reserved thread was not tied until the incision
      was completely closed. RESULTS: After operation, the reserved threads were
      tightened and tied for 1 time in 6 patients, 2 times in 23 patients, 3 times in
      27 patients, 4 times in 11 patients. Postoperative closure time ranged from 3 to
      9 days, with an average of 6.2 days. All the incisions got delayed primary
      healing. CONCLUSION: The method of serial tightening of reserved suture threads
      to close delayed incision closure avoids a second operation, which is simple and
      obtains a fine result.

PMID- 25577922
TI  - [Diaphyseal tuberculosis of left femur misdiagnosed as chronic suppurative
      osteomyelitis: a case report].

PMID- 25577923
TI  - [Clinical characteristics of triceps brachii tendon rupture at olecranon ending].
AB  - OBJECTIVE: To observe the clinical characteristics of triceps brachii tendon
      rupture at olecranon ending. METHODS: From June 2005 to November 2011,19 patients
      with triceps brachii tendon rupture at olecranon ending were treated with
      surgical technique. Among the 19 patients, 7 patients were male, with an average
      age of 24.1 years old (ranged, 15 to 41 years old); 12 patients were female, with
      an average age of 51.4 years old (ranged, 16 to 73 years old). Eight patients had
      injuries in the left elbows, and 11 patients had injuries in right elbows.
      Seventeen patients had injuries induced by walking fall and 2 patients had
      injuries induced by falling down. Thirteen patients were simple triceps brachii
      tendon rupture at olecranon ending, 6 patients were associated with other elbow
      injuries. Five patients were associated with radial fracture; 1 patient with
      capitellum fracture; 1 patient with coronoid process fracture; 1 patient with
      epitrochlear. All the lateral radiographs of the injuried elbow demenstrated the
      flecks of avulsed osseous material from the olecranon (flake sign). The
      associated injuries had the homologus presence. All the patients were treated
      with surgical techniques:15 patients were treated with figure-of-eight tension
      band wire; figure-of-eight tension band wire and Kirschner wire in 1 patient;
      wire cerclage in 1 patient; nonabsorbable suture in 2 patients. The associated
      injuries were treated simultaneously. Plaster was applied after operation in 2
      patients with heavier elbow associated injuries, other patients without any
      external fixation. The Mayo elbow score were observed to determinate the function
      of the elbow. RESULTS: All the patients were followed up, 1 patient died of other
      disease at one year after operation, the other 18 patients were followed up with
      an average of 47.9 months (ranged from 14 to 91 months). According to the Mayo
      elbow score, 16 patients got an excellent result and 2 good. CONCLUSION:
      Traumatic rupture of triceps brachii tendon at olecranon ending is not a rare
      injury, which is common in female older than fifty and in male younger then
      thirty. Surgical results are generally excellent. But dysfunction frequently
      remains in patients with associated elbow injuries.

PMID- 25577924
TI  - [Three-column plate internal fixation for the treatment of complex tibial plateau
      fracture through antero-midline and postero-medial approaches].
AB  - OBJECTIVE: To study technique and clinical therapeutic effects of internal
      fixation with three-column plates for the treatment of complex tibial plateau
      fractures through antero-midline and postero-medial approaches. METHODS: From
      January 2010 to December 2012, 28 patients with complex tibial plateau fractures
      were treated with internal fixation using three-column plates through antero
      midline and postero-medial approaches. There were 17 males and 11 females, with
      an average age of 45.3 years old (ranged, 28 to 64 years old). Twelve patients
      had injuries in the left side and 16 patients had injuries in the right side.
      According to Schatzker classification, 12 patients were type V, 16 patients were
      type VI. According to three-column classification, all the patients had injuries
      of lateral, medial and posterior columns. The mean interval from injury to
      operation was 9.4 days (ranged, 6 to 15 days). The main clinical symptoms were
      knee joint swelling, deformity and limitation of motion before operation. The X
      ray and CT showed all patients had complex tibial plateau fractures, which
      involved in the lateral, medial and posterior columns. The therapeutic effects
      were evaluated by fracture healing time, hospital for special surgery knee score
      (HSS) at one year after operation. The indexes such as tibial plateau-tibial
      shaft angle (TPA), posterior slope angle (PA) and femoral-tibial angle (FfA) were
      compared between immediate postoperation and one year after operation. RESULTS:
      All incisions primarily healed without postoperative complications such as
      infection and cutaneous necrosis. All the patients were followed up, and the
      duration ranged from 12 to 24 months, with a mean of 18.1 months. The bone union
      time ranged from 5 to 10 months (mean, 7.8 months) after operation. Knee joint
      swelling and pain disappeared after bony union, and joint function completely
      recovered. The results of hospital for special surgery knee score (HSS) was 27.81
      +/- 2.17 in pain, 19.52 +/- 2.05 in function,15.82 +/- 1.73 in passive range of
      motion, 8.51 +/- 1.32 in muscle strength, 8.33 +/- 1.08 in flexion deformity,
      9.36 +/- 0.52 in joint stability, and the total mean score was 89.35 +/- 3.19.
      According to results of HSS, 20 patients got an excellent result, 5 good,2 fair
      and 1 poor. There were no significant differences in tibial plateau-tibial shaft
      angle (TPA), posterior slope angle (PA) and femoral-tibial angle (FTA) between
      immediate postoperation and one year after operation. CONCLUSION: Three-column
      plate internal fixation for the treatment of complex tibial plateau fractures
      through antero-midline and posteromedial approaches is effective to achieve
      anatomic reduction,rigid internal fixation and early functional exercise.

PMID- 25577925
TI  - [Treatment of type C3 distal radius fractures with AO 2.4 mm locking plate system
      after manipulative reduction].
AB  - OBJECTIVE: To summarize our experiences in the treatment of type C3 (AO/OTA)
      distal radius fractures fixed with AO 2.4 mm locking plates combined with
      percutaneous pinning after manipulative reduction. METHODS: From May 2009 to
      March 2012, 19 patients (2 cases of both sides) with type C3 (AO/OTA) distal
      radius fractures were treated with volar locking plates combined with
      percutaneous pinning for distal radius after manipulative reduction. Among the
      patients, the average age was (45.3 +/- 17.4) years old (ranged, 31 to 66 years
      old). The fracture were complicated with ulnar styloid fracture in 14 wrists and
      6 wrists had distal radioulnar joint instability. All the patients had closed
      fracture and the mean duration was (6.7 +/- 3.5) days (4.5 to 9 days). The Henry
      approach was applied to expose the fracture site. Joint capsule and ligaments
      were retained for indirect reduction. After indirect reduction, the poking
      reduction technique was used to correct the residual compression, and congruence
      of distal ulnar radial joint was verified under fluorscopic guidance. Styloid
      process was first pinned percutaneously and then AO 2.4 mm volar locking plate
      was used to support rigid fixation. The fractures complicated with distal
      radioulnar joint instability and ulnar styloid fracture were treated with forearm
      plaster support in supination for 6 weeks. RESULTS: Nineteen patients (21 wrists)
      were followed up for an average duration of 10.5 months (ranged, 7 to 17 months).
      Radiographic bone union of distal radius was achieved in all cases, nonunion of
      the ulnar styloid occurred in 3 cases, and no distal radioulnar joint instability
      occurred. Tendon irritation was found in 2 cases and disappeared after the
      internal fixation was removed. The volar tilt, radial angle, radial length,
      incongruence of articular surface and distal radioulnar joint were observed at
      the follow-up. According to Batra and Gupta scoring system, 13 wrists were
      assessed to have a score of more than 80, 5 wrists 70 to 90, 3 wrists less than
      70. Meanwhile, the subjective and objective evaluation was executed,range of
      motion of wrist, residual deformity and complications were observed. According to
      Sarmiento's modification of the system of Gartland and Werley, 17 wrists got an
      excellent result, 3 good and 1 fair. CONCLUSION: Type C3 (AO/OTA) distal radius
      fractures could be managed with manipulative reduction. Locking plate internal
      fixation combined with percutaneous pinning can offer enough support for early
      mobilization and rehabilitation, resulting in a better clinical outcome and
      satisfactory prognosis.

PMID- 25577926
TI  - [Cause analysis of postoperative pain after total knee arthroplasty].
AB  - Total knee arthroplasty (TKA) has been successfully applied for the treatment of
      the knee pathology at the end stage such as osteoarthritis and rheumatoid
      arthritis. Although TKA has became a very mature technology, some patients still
      suffer from the persistent pain after surgery. The cause of this pain have been
      recognized as the operation or technical error in most cases, and it usually
      requires a surgical intervention. Only when the cause of pain is judged
      accurately, can the operation and other factors be estimated correctly,
      determining the appropriate treatment methods. In the article, the causes of the
      post-operative pain after TKA are reviewed, which may be helpful to study the
      causes of the pain, and to decrease the occurrence incidence of pain.

PMID- 25577927
TI  - [Relations between equilibrium and dynamics at the turn of the 17th and 18th
      centuries].
AB  - This article investigates the reception of Galileo and Descartes' principles of
      statics in the works of some French scientists in the second half of seventeenth
      century, tracing their importance for the genesis of a concept of force. Through
      an examination of the link between statics and dynamics--especially concerning
      the phenomena of collision and the motion of falling bodies--it will be shown,
      first, that these principles of statics actually contributed to the genesis of
      dynamics; secondly, that the authors examined in this article managed to unify
      the various fields of mechanics by building a common axiomatic basis, and,
      thirdly, that there exists a conceptual identity between actions in engines and
      actions in dynamic phenomena. The evidence brought fourth in this articles
      challenges the view according to which statics, and more particularly the law of
      the lever, was an obstacle for the development of dynamics, and particularly for
      the conceptualization of force.

PMID- 25577928
TI  - Nothing new under the sun: post-traumatic stress disorders in the ancient world.
AB  - Herodotus' account of the Athenian spear carrier Epizelus' psychogenic mutism
      following the Marathon Wars is usually cited as the first documented account of
      post-traumatic stress disorders in historical literature. This paper describes
      much earlier accounts of post combat disorders that were recorded as occurring in
      Mesopotamia (present day Iraq) during the Assyrian dynasty (1300-609 BC). The
      descriptions in this paper include many symptoms of what we would now identify in
      current diagnostic classification systems as post-traumatic stress disorders;
      including flashbacks, sleep disturbance and low mood. The Mesopotamians explain
      the disorder in terms of spirit affliction; the spirit of those enemies whom the
      patient had killed during battle causing the symptoms.

PMID- 25577929
TI  - Long life, natural death. The learned ideal of dying in late medieval
      commentaries on Avicenna's Canon.
AB  - Within late medieval learned medicine, natural death functioned both as a
      theoretical concept and as a goal for practice. Late medieval commentaries on
      Avicenna's Canon are used as source material in this study, in order to
      investigate the ways in which these learned medical authors envisaged natural
      death. The findings are compared to descriptions of natural death by natural
      philosophers, and to ideals of dying in broader medieval culture. According to
      the physicians, natural death was caused by the extinction of innate heat, due to
      a lack of innate moisture. They discussed natural death in relation to regimen,
      as the right regimen protected the body's heat and moisture, and thus helped a
      patient to keep natural death aloof. So, in order to think about natural death,
      the physicians turned to the whole of life, during which heat dried out moisture
      and regimens ought to be followed. By contrast, natural philosophers tended to
      focus on the moment of death itself. The comparison of natural death with the
      Good Death in broad medieval culture highlights the amoral nature of the natural
      death.

PMID- 25577944
TI  - Confirmation of the molecular structure of tetramethylene diperoxide dicarbamide
      (TMDD) and its sensitiveness properties.
AB  - Conjecture existed as to the molecular structure of the crystalline organic
      peroxide reaction product derived from the acidified aqueous mixture of urea,
      formaldehyde, and hydrogen peroxide. This study used X-ray crystal structure
      determination to unequivocally define the reaction product as the 14-membered
      ring structure tetramethylene diperoxide dicarbamide (TMDD). Crystals of TMDD
      belong to the monoclinic space group Pc, a = 4.587(4), b = 16.080(2), c =
      6.690(5) A, beta = 107.44(5) degrees . The crystal contains one
      crystallographically independent molecule with approximate Cs symmetry.
      Intramolecular pi-stacking of the carbonyl groups is a feature, while
      intermolecular H-bonding between the N-H and C?O functionalities affords linear
      polymeric strands that is associated with the extremely fine needle crystal
      morphology that necessitated synchrotron radiation for the structure
      determination. Sensitiveness testing examining susceptibility to initiate due to
      heat, impact, friction, and electrostatic stimuli was conducted to gauge the
      hazards associated with the material. It was revealed to be a primary explosive,
      particularly susceptible to impact initiation. 

PMID- 25577945
TI  - Analysis and modeling of metals release from MBT wastes through batch and up-flow
      column tests.
AB  - The leaching behavior of wastes coming out from Mechanical Biological Treatment
      (MBT) plants is still poorly investigated in literature. This work presents an
      attempt to provide a deeper insight about the contaminants release from this type
      of waste. To this end, results of several batch and up-flow percolation tests,
      carried out on different biologically treated waste samples collected from an
      Italian MBT plant, are reported. The obtained results showed that, despite MBT
      wastes are characterized by relatively high heavy metals content, only a limited
      amount was actually soluble and thus bioavailable. Namely, the release percentage
      was generally lower than 5% of the total content with the only exception of
      dissolved organic carbon (DOC), Zn, Ni and Co with release percentages up to 20%.
      The information provided by the different tests also allowed to highlight some
      key factors governing the kinetics release of DOC and metals from this type of
      material. In particular, results of up-flow column percolation tests showed that
      metals such as Cr, Mg, Ni and Zn followed essentially the leaching trend of DOC
      suggesting that these elements were mainly released as organo-compounds.
      Actually, a strong linear correlation (R(2) > 0.8) between DOC and metals
      concentration in eluates was observed, especially for Cr, Ni and Zn (R(2)>0.94).
      Thus, combining the results of batch and up-flow column percolation tests,
      partition coefficients between DOC and metals concentration were derived. These
      data, coupled with a simplified screening model for DOC release, allowed to get a
      very good prediction of metal release during the different column tests. Finally,
      combining the experimental data with a simplified model provided some useful
      indications for the evaluation of long-term emissions from this type of waste in
      landfill disposal scenarios.

PMID- 25577946
TI  - Accumulation of 24S-hydroxycholesterol in neuronal SK-N-BE cells treated with
      hexacosanoic acid (C26:0): argument in favor of 24S-hydroxycholesterol as a
      potential biomarker of neurolipotoxicity.
AB  - Cholesterol oxide derivatives (oxysterols) are viewed as potential biomarkers of
      neurodegenerative diseases. 24S-hydroxycholesterol, an oxysterol produced only in
      brain neurons, is often found for unknown reasons in increased levels in the
      plasma in patients with neurodegenerative diseases. On human neuronal SK-N-BE
      cells treated with hexacosanoic acid (C26:0) identified at increased levels in
      the tissues and plasma of patients with peroxisomal leukodystrophies and
      Alzheimer's disease, we observed increased level of 24S-hydroxycholesterol
      associated with C26:0 induced lipotoxicity. This finding reinforces the
      hypothesis suggesting that 24S-hydroxycholesterol could constitute a biomarker of
      neurotoxicity. 

PMID- 25577947
TI  - 1903 manuscript revived: Cerebral disturbances in multiple sclerosis (Des
      troubles cerebraux dans la sclerose en plaques) by Raymond Cestan (1872-1933) and
      Claudien Philippe (1866-1903).
AB  - Philanthropy aimed at helping medical research has been around for a long time.
      In the 19th century, cash awards were distributed by the French Academy of
      Medicine according to criteria determined by each generous donor. It was thus
      that Mrs. Bernard de Civrieux endowed the Academy each year with the task of
      supporting one or more laureates whose work furthered understanding of "nervous
      diseases". In 1903, Raymond Cestan (1872-1933) and Claudien Philippe (1866-1903)
      were selected for their dissertation on "cerebral disturbances" during multiple
      sclerosis with clinical as well as anatomical-pathological effects. Never
      published, this innovative manuscript, taken from the library of Fulgence Raymond
      (1844-1910), will be analysed here after a brief biography of each author. 

PMID- 25577948
TI  - Assessment of stress and self-efficacy for the NIH Toolbox for Neurological and
      Behavioral Function.
AB  - BACKGROUND AND OBJECTIVES: The NIH Toolbox for Neurological and Behavioral
      Function assessment battery contains measures in the domains of cognitive
      function, motor function, sensory function, and emotional health. It was designed
      for use in epidemiological and clinical trials health-related research. DESIGN:
      This paper describes the first phase of instrument development for the stress and
      self-efficacy subdomain of emotional health. Based on an extensive literature
      review and expert consultation, 127 measures were initially considered for
      inclusion in this subdomain, including measures of stress, self-efficacy, emotion
      regulation, and coping. RESULTS: Several measures, including emotion regulation
      and measures of coping strategies, did not meet criteria that were a priori
      established for inclusion. Psychometric properties of the remaining candidate
      measures were evaluated using data from five independent samples (combined N =
      3175). Confirmatory and exploratory factor analyses indicated the Perceived
      Stress Scale and the General Self-Efficacy Scale each assessed single dimensions.
      CONCLUSIONS: Based on their psychometric performance, these two instruments were
      selected for inclusion and subsequent national norming for the NIH Toolbox.

PMID- 25577949
TI  - An examination of the nutrient content and on-package marketing of novel
      beverages.
AB  - Changing regulatory approaches to fortification in Canada have enabled the
      expansion of the novel beverage market, but the nutritional implications of these
      new products are poorly understood. This study assessed the micronutrient
      composition of energy drinks, vitamin waters, and novel juices sold in Canadian
      supermarkets, and critically examined their on-package marketing at 2 time
      points: 2010-2011, when they were regulated as Natural Health Products, and 2014,
      when they fell under food regulations. We examined changes in micronutrient
      composition and on-package marketing among a sample of novel beverages (n = 46)
      over time, compared micronutrient content with Dietary Reference Intakes and the
      results of the 2004 Canadian Community Health Survey to assess potential
      benefits, and conducted a content analysis of product labels. The median number
      of nutrients per product was 4.5, with vitamins B6, B12, C, and niacin most
      commonly added. Almost every beverage provided at least 1 nutrient in excess of
      requirements, and most contained 3 or more nutrients at such levels. With the
      exception of vitamin C, there was no discernible prevalence of inadequacy among
      young Canadian adults for the nutrients. Product labels promoted performance and
      emotional benefits related to nutrient formulations that go beyond conventional
      nutritional science. Label graphics continued to communicate these attributes
      even after reformatting to comply with food regulations. In contrast with the on
      package marketing of novel beverages, there is little evidence that consumers
      stand to benefit from the micronutrients most commonly found in these products. 

PMID- 25577950
TI  - Combination of redox-active ligand and lewis acid for dioxygen reduction with pi
      bound molybdenum-quinonoid complexes.
AB  - A series of pi-bound Mo-quinonoid complexes supported by pendant phosphines have
      been synthesized. Structural characterization revealed strong metal-arene
      interactions between Mo and the pi system of the quinonoid fragment. The Mo
      catechol complex (2a) was found to react within minutes with 0.5 equiv of O(2) to
      yield a Mo-quinone complex (3), H(2)O, and CO. Si- and B-protected Mo-catecholate
      complexes also react with O(2) to yield 3 along with (R(2)SiO)n and (ArBO)(3)
      byproducts, respectively. Formally, the Mo-catecholate fragment provides two
      electrons, while the elements bound to the catecholate moiety act as acceptors
      for the O(2) oxygens. Unreactive by itself, the Mo-dimethyl catecholate analogue
      reduces O(2) in the presence of added Lewis acid, B(C(6)F(5))(3), to generate a
      Mo(I) species and a bis(borane)-supported peroxide dianion,
      [[(F(5)C(6))(3)B](2)O(2)(2-)], demonstrating single-electron-transfer chemistry
      from Mo to the O(2) moiety. The intramolecular combination of a molybdenum
      center, redox-active ligand, and Lewis acid reduces O(2) with pendant acids
      weaker than B(C(6)F(5))(3). Overall, the pi-bound catecholate moiety acts as a
      two-electron donor. A mechanism is proposed in which O(2) is reduced through an
      initial one-electron transfer, coupled with transfer of the Lewis acidic moiety
      bound to the quinonoid oxygen atoms to the reduced O(2) species.

PMID- 25577951
TI  - Prevention and treatment of the post-thrombotic syndrome and of the chronic
      thromboembolic pulmonary hypertension.
AB  - Post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension
      (CTEPH) are late complications of venous thromboembolism. The purpose of this
      review is to present and discuss recently published studies that have improved
      our knowledge of PTS and CTEPH. The current understanding of the pathophysiology
      of PTS and CTEPH is discussed as well as the importance of chronic residual
      venous thrombosis, some polymorphisms of plasminogen activator inhibitor-1, and
      the current concept of misguided thrombus resolution. The surprising finding that
      elastic compression stockings may not be effective in preventing PTS and the
      novel medical treatment in CTEPH are discussed in detail. Novel direct oral
      anticoagulants show potential for prevention of PTS. No firm conclusions can be
      drawn on the efficacy of elastic stockings. Novel treatments of CTEPH for
      inoperable patients and those with persistent pulmonary hypertension after
      surgery have become available and further research on wider indication for their
      use is urgently needed. 

PMID- 25577952
TI  - Profiles of mRNA expression of related genes in the duck hypothalamus-pituitary
      growth axis during embryonic and early post-hatch development.
AB  - In this study, the ontogeny of body and liver weight and the pattern of related
      gene mRNA expression in the hypothalamus-pituitary growth axis (HPGA) of two
      different duck breeds (Anas platyrhynchos domestica) were compared during
      embryonic and post-hatch development. Duck hypothalamic growth hormone release
      hormone (GHRH), somatostatin (SS), pituitary growth hormone (GH), liver growth
      hormone receptor (GHR) and insulin-like growth factor-I (IGF-1) mRNA were first
      detected on the 13th embryonic day. During early duck development, SS maintained
      a lower expression status, whereas the other four genes exhibited highly
      significant variations in an age-specific manner. Highly significant breed
      specificity was observed with respect to hepatic IGF-1 mRNA expression, which
      showed a significant breed-age interaction effect. Compared with previous studies
      on chickens, significant species differences were observed regarding the mRNA
      expression of bird embryonic HPGA-related genes. During early development, highly
      significant breed and age specificity were observed with respect to developmental
      changes in body and liver weight, and varying degrees of significant linear
      correlation were found between these performances and the mRNA expression of HPGA
      related genes in the duck HPGA. These results suggest that different genetic
      backgrounds may lead to differences in duck growth and HPGA-related gene mRNA
      expression, and the differential mRNA expression of related genes in the duck
      HPGA may be particularly important in the early growth of ducks. Furthermore,
      hepatic IGF-1 mRNA expression presented highly significant breed specificity, and
      evidence suggests the involvement of hepatic IGF-1 in mediating genetic effects
      on embryo and offspring growth in ducks. 

PMID- 25577953
TI  - Income inequality and health: a causal review.
AB  - There is a very large literature examining income inequality in relation to
      health. Early reviews came to different interpretations of the evidence, though a
      large majority of studies reported that health tended to be worse in more unequal
      societies. More recent studies, not included in those reviews, provide
      substantial new evidence. Our purpose in this paper is to assess whether or not
      wider income differences play a causal role leading to worse health. We conducted
      a literature review within an epidemiological causal framework and inferred the
      likelihood of a causal relationship between income inequality and health
      (including violence) by considering the evidence as a whole. The body of evidence
      strongly suggests that income inequality affects population health and wellbeing.
      The major causal criteria of temporality, biological plausibility, consistency
      and lack of alternative explanations are well supported. Of the small minority of
      studies which find no association, most can be explained by income inequality
      being measured at an inappropriate scale, the inclusion of mediating variables as
      controls, the use of subjective rather than objective measures of health, or
      follow up periods which are too short. The evidence that large income differences
      have damaging health and social consequences is strong and in most countries
      inequality is increasing. Narrowing the gap will improve the health and wellbeing
      of populations. 

PMID- 25577955
TI  - Dual HER2 inhibition and paclitaxel in metastatic breast cancer.

PMID- 25577956
TI  - HPV vaccination not linked to multiple sclerosis.

PMID- 25577954
TI  - Is avolition in schizophrenia associated with a deficit of dorsal caudate
      activity? A functional magnetic resonance imaging study during reward
      anticipation and feedback.
AB  - BACKGROUND: The neurobiological underpinnings of avolition in schizophrenia
      remain unclear. Most brain imaging research has focused on reward prediction
      deficit and on ventral striatum dysfunction, but findings are not consistent. In
      the light of accumulating evidence that both ventral striatum and dorsal caudate
      play a key role in motivation, we investigated ventral striatum and dorsal
      caudate activation during processing of reward or loss in patients with
      schizophrenia. METHOD: We used functional magnetic resonance imaging to study
      brain activation during a Monetary Incentive Delay task in patients with
      schizophrenia, treated with second-generation antipsychotics only, and in healthy
      controls (HC). We also assessed the relationships of ventral striatum and dorsal
      caudate activation with measures of hedonic experience and motivation. RESULTS:
      The whole patient group had lower motivation but comparable hedonic experience
      and striatal activation than HC. Patients with high avolition scores showed lower
      dorsal caudate activation than both HC and patients with low avolition scores. A
      lower dorsal caudate activation was also observed in patients with deficit
      schizophrenia compared to HC and patients with non-deficit schizophrenia. Dorsal
      caudate activity during reward anticipation was significantly associated with
      avolition, but not with anhedonia in the patient group. CONCLUSIONS: These
      findings suggest that avolition in schizophrenia is linked to dorsal caudate
      hypoactivation.

PMID- 25577957
TI  - Tyrosinase gene mutations in the Chinese Han population with OCA1.
AB  - Oculocutaneous albinism (OCA) is a heterogeneous autosomal recessive genetic
      disorder that affects melanin synthesis. OCA results in reduced or absent
      pigmentation in the hair, skin and eyes. Type 1 OCA (OCA1) is the result of
      tyrosinase (TYR) gene mutations and is a severe disease type. This study
      investigated TYR mutations in a Chinese cohort with OCA1. This study included two
      parts: patient genetic study and prenatal genetic diagnosis. A total of 30 OCA1
      patients were subjected to TYR gene mutation analysis. Ten pedigrees were
      included for prenatal genetic diagnosis. A total of 100 unrelated healthy Chinese
      individuals were genotyped for controls. The coding sequence and the intron/exon
      junctions of TYR were analysed by bidirectional DNA sequencing. In this study, 20
      mutations were identified, four of which were novel. Of these 30 OCA1 patients,
      25 patients were TYR compound heterozygous; two patients carried homozygous TYR
      mutations; and three were heterozygous. Among the ten prenatally genotyped
      fetuses, three fetuses carried compound heterozygous mutations and seven carried
      no mutation or only one mutant allele of TYR and appeared normal at birth. In
      conclusion, we identified four novel TYR mutations and showed that molecular
      based prenatal screening to detect TYR mutations in a fetus at risk for OCA1
      provided essential information for genetic counselling of couples at risk.

PMID- 25577958
TI  - Cognitive recovery by chronic activation of the large-conductance calcium
      activated potassium channel in a mouse model of Alzheimer's disease.
AB  - We previously showed that activity of the large conductance calcium-activated
      potassium (Big-K; BK) channels is suppressed in 3xTg Alzheimer disease (AD) model
      mice. However, its behavioral significance is not known. In the present report,
      ventricular injection of the BK channel activator isopimaric acid (ISO) was
      conducted to examine whether BK channel activation ameliorates cognition in 3xTg
      mice. The novel object recognition (NOR) test revealed that chronic injection of
      ISO improved non-spatial memory in 3xTg mice. In the Morris water maze, the probe
      test demonstrated an improved spatial memory after ISO injection.
      Electrophysiological underpinnings of the ISO effect were then examined in slices
      obtained from the mice after behavior. At hippocampal CA1 synapses, the basic
      synaptic transmission was abnormally elevated and long-term potentiation (LTP)
      was partially suppressed in 3xTg mice. These were both recovered by ISO
      treatment. We then confirmed suppressed BK channel activity in 3xTg mice by
      measuring the half-width of evoked action potentials. This was also recovered by
      ISO treatment. We previously showed that the recovery of BK channel activity
      accompanies reduction of neuronal excitability in pyramidal cells. Here again,
      pyramidal cell excitability, as assessed by calculating the frequency of evoked
      spikes, was elevated in the 3xTg mouse and was normalized by ISO. ELISA
      experiments demonstrated an ISO-induced reduction of Abeta1-42 content in
      hippocampal tissue in 3xTg mice. The present study thus suggests a potential
      therapeutic utility of BK channel activators for AD. 

PMID- 25577959
TI  - Spectrum of perforin gene mutations in familial hemophagocytic
      lymphohistiocytosis (FHL) patients in India.
AB  - BACKGROUND: Inherited perforin deficiency is a rare autosomal recessive disorder
      that causes severe form of hemophagocytic lymphohistiocytosis (FHL2). The main
      aim of this study was to analyze the nature of gene mutations in a cohort of
      Indian patients with FHL2 and to utilize this knowledge for genetic counseling
      and prenatal diagnosis. METHODS: 13 HLH patients with abnormal perforin
      expression on NK cells by flow cytometry were included in the study. The entire
      coding region and intronic splice sites of the PRF1 gene were sequenced from the
      genomic DNA of these patients. RESULTS: 10 patients from the present series had
      an early presentation with severe clinical manifestations, while 3 had a delayed
      onset with unusual presenting features viz Hodgkin's lymphoma, tuberculosis and
      acute lymphoblastic leukemia. Sequence analysis revealed 11 different mutations
      (8 novel and 3 previously reported) spread over the entire coding region of PRF1
      gene. Missense mutation Trp129Ser in heterozygous state was present in all the 3
      patients with a delayed onset of the disease. CONCLUSION: A wide heterogeneity
      was observed in the nature of mutations in Indian FHL2 patients. Molecular
      characterization of PRF1 gene was not only used in the confirmation of diagnosis
      but also in genetic counseling and pre-natal diagnosis in affected families.

PMID- 25577960
TI  - 3-dimensional analysis of scaphoid fracture angle morphology.
AB  - PURPOSE: Scaphoid fractures are classified according to their 2-dimensional
      radiographic appearance, and transverse waist fractures are considered the most
      common. Our hypothesis was that most scaphoid fractures are not perpendicular to
      the longitudinal axis of the scaphoid (ie, not transverse). METHODS: Computerized
      3-dimensional analyses were performed on 124 computed tomography scans of acute
      scaphoid fractures. Thirty of the fractures were displaced and virtually reduced.
      The angle between the scaphoid's first principal axis (longitudinal axis) and the
      fracture plane was analyzed for location and displacement. The distal radius
      articular surface was used to depict the volar-dorsal vector of the wrist.
      RESULTS: There were 86 fractures of the waist, 13 of the distal third, and 25 of
      the proximal third. The average angle between the scaphoid longitudinal axis and
      the fracture plane was 53 degrees  for all fractures and 56 degrees  for waist
      fractures, both differing significantly from a 90 degrees , transverse fracture.
      The majority of fracture planes were found to have a volar distal to dorsal
      proximal (horizontal oblique) inclination relative to the volar-dorsal vector.
      CONCLUSIONS: Most waist fractures were horizontal oblique and not transverse.
      According to these findings, fixation of all fractures along the longitudinal
      axis of the scaphoid may not be the optimal mode of fixation for most. A
      different approach may be needed in accordance with the fracture plane. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Diagnostic II.

PMID- 25577961
TI  - Recurrent pigmented villonodular synovitis and multifocal giant cell tumor of the
      tendon sheath: case report.
AB  - Intra- and extra-articular giant cell tumor of tendon sheath (GCTTS) and
      pigmented villonodular synovitis (PVNS) are histologically similar, usually
      benign tumors that can be characterized by synovial involvement (GCTTS) or
      overgrowth (PVNS). These tumors are most often found in the knee and digits of
      the hand. Although recurrence is a common feature of both conditions, multifocal
      lesions are rare. We present an unusual case of multifocal, recurrent, bilateral
      GCTTS/PVNS involving both upper and lower extremities. Recurrent right ankle and
      right index finger masses, in addition to masses on the right small finger and
      left thumb, were excised over a 14-year period. 

PMID- 25577962
TI  - Use of metabolomics to elucidate the metabolic perturbation associated with
      hypertension in a black South African male cohort: the SABPA study.
AB  - There is concern about the increasing burden of essential hypertension in urban
      dwelling black South Africans, especially males. Several studies have
      investigated urbanization and hypertension in South Africans, but in-depth
      metabolomics studies on these urbanized hypertensives are still lacking. We aimed
      to investigate hypertension via two metabolomics methods in order to explore
      underlying biological mechanisms, demonstrating the effectiveness of these
      methods in cardiovascular research. A comprehensive characterization of a group
      (n = 25) of black male South Africans was performed using urinary gas
      chromatography-mass spectrometry and liquid chromatography-mass spectrometry
      metabolic profiling in conjunction with 24-hour ambulatory blood pressure
      readings and anthropometric, clinical, and biochemical markers. Average 24-hour
      blood pressure readings served as the grouping variable, and test subjects were
      divided into quintiles. Statistical analyses were performed on Quintile 1
      (normotensive subjects) and Quintile 5 (extreme hypertensive subjects). After
      feature selection was performed, several metabolites and cardiometabolic risk
      markers, including abdominal obesity and markers of liver damage, inflammation,
      and oxidative stress were significantly perturbed in Quintile 5 (hypertensives)
      compared with Quintile 1 (P < .05). Pathway analysis revealed perturbations in
      several systems involved in ethanol metabolism via shifted global NADH/NAD(+)
      ratio. Although alcohol abuse has been established as a risk factor for
      hypertension, this study illustrated a metabolic perturbation associated with
      alcohol abuse, contributing to the development of hypertension-possibly by
      altering bioenergetics through a shift in the NADH/NAD(+) ratio. Following this
      finding, future intervention studies on alcohol moderation, as well as further
      enhancement of metabolomics methods in cardiovascular research are highly
      recommended. 

PMID- 25577971
TI  - Effects of multi-frequency power ultrasound on the enzymolysis and structural
      characteristics of corn gluten meal.
AB  - The aim of this study was to investigate the effect of multi-frequency power
      ultrasound (sweeping frequency and pulsed ultrasound (SFPU) and sequential dual
      frequency ultrasound (SDFU)) on the enzymolysis of corn gluten meal (CGM) and on
      the structures of the major protein fractions (zein, glutelin) of CGM. The
      results showed that multi-frequency power ultrasound pretreatments improved
      significantly (P<0.05) the degree of hydrolysis and conversion rate of CGM. The
      changes in UV-Vis spectra, fluorescence emission spectra, surface hydrophobicity
      (H0), and the content of SH and SS groups indicated unfolding of zein and
      glutelin by ultrasound. The circular dichroism analysis showed that both
      pretreatments decreased alpha-helix and increased beta-sheet of glutelin. The
      SFPU pretreatment had little impact on the secondary structure of zein, while the
      SDFU increased the alpha-helix and decreased the beta-sheet remarkably. Scanning
      electron microscope indicated that both pretreatments destroyed the
      microstructures of glutelin and CGM, reduced the particle size of zein despite
      that the SDFU induced aggregation was observed. In conclusion, multi-frequency
      power ultrasound pretreatment is an efficient method in protein proteolysis due
      to its sonochemistry effect on the molecular conformation as well as on the
      microstructure of protein. 

PMID- 25577972
TI  - Making the hospital a safer place by sonochemical coating of all its textiles
      with antibacterial nanoparticles.
AB  - The ability to scale-up the sonochemical coating of medical textiles with
      antibacterial nanoparticles is demonstrated in the current paper. A roll-to-roll
      pilot installation to coat textiles was built taking into consideration the
      requirements of the sonochemical process. A long-run experiment was conducted in
      which 2500 m of fabric were coated with antibacterial ZnO nanoparticles (NPs).
      The metal oxide NPs were deposited from an ethanol:water solution. In this
      continuous process a uniform concentration of coated NPs over the length/width of
      the fabric was achieved. The antibacterial efficiency of the sonochemically
      coated textiles was validated in a hospital environment by a reduction in the
      occurrence of nosocomial infections. NP-coated bed sheets, patient gowns, pillow
      cover, and bed covers were used by 21 patients. For comparison 16 patients used
      regular textiles. The clinical data indicated the reduced occurrence of hospital
      acquired infections when using the metal oxide NP-coated textiles. In order to
      reduce the cost of the coating process and considering safety issues during
      manufacturing, the solvent (ethanol:water) (9:1 v:v) used for the long-run
      experiment, was replaced by water. Although lesser amounts of ZnO NPs were
      deposited on the fabric in the water-based process the antibacterial activity of
      the textiles was preserved due to the smaller size of the particles.

PMID- 25577973
TI  - The Impact of Pelvic Venous Pressure on Blood Loss during Open Radical Cystectomy
      and Urinary Diversion: Results of a Secondary Analysis of a Randomized Clinical
      Trial.
AB  - PURPOSE: Blood loss and blood substitution are associated with higher morbidity
      after major abdominal surgery. During major liver resection low local venous
      pressure decreases blood loss. Ambiguity persists concerning the impact of local
      venous pressure on blood loss during open radical cystectomy. We determined the
      association between intraoperative blood loss and pelvic venous pressure as well
      as factors affecting pelvic venous pressure. MATERIALS AND METHODS: In this
      single center, double-blind, randomized trial pelvic venous pressure was measured
      in 82 patients in a norepinephrine-low volume group and in 81 controls with
      liberal hydration. As secondary analysis patients from each arm were stratified
      into subgroups with pelvic venous pressure less than 5 mm Hg, or 5 or greater as
      measured after cystectomy, which is the optimal cutoff for identifying patients
      with relevant blood loss according to the Youden index. RESULTS: Median blood
      loss was 800 ml (range 300 to 1,600) in 55 of 163 patients (34%) with pelvic
      venous pressure less than 5 mm Hg and 1,200 ml (range 400 to 3,000) in 108 of 163
      (66%) with pelvic venous pressure 5 mm Hg or greater (p <0.0001). Pelvic venous
      pressure less than 5 mm Hg was measured in 42 of 82 patients (51%) in the
      norepinephrine-low volume group and in 13 of 81 controls (16%) (p <0.0001).
      Pelvic venous pressure decreased significantly after removing abdominal packing
      and abdominal lifting in each group at all time points, that is at the beginning
      and end of pelvic lymph node dissection, and the end of cystectomy (p <0.0001).
      No correlation was detected between pelvic venous pressure and central venous
      pressure. CONCLUSIONS: Blood loss was significantly decreased in patients with
      low pelvic venous pressure. Factors affecting pelvic venous pressure were fluid
      management and abdominal packing.

PMID- 25577974
TI  - The renal effects of prenatal testosterone in rats.
AB  - PURPOSE: Previous studies have shown that prenatal testosterone affects the
      development of not only reproductive organs but also the brain and even glucose
      metabolism. Whether prenatal testosterone influences the kidney development is
      largely unknown. We analyzed whether testosterone modulation during prenatal
      development would affect renal function and the number of nephrons in adult
      offspring. MATERIALS AND METHODS: Pregnant rats were treated with olive oil,
      testosterone (2 mg/kg), the androgen receptor blocker flutamide (5 mg/kg) or
      testosterone plus flutamide via daily intramuscular injections from gestation day
      14 until delivery. Renal histology and functional parameters were assessed in
      male and female adult offspring. Macerated kidneys were used for nephron
      counting. RESULTS: Prenatal testosterone administration increased proteinuria in
      male rats by 256%. A similar 134% effect in female rats was not statistically
      significant. This effect was prevented when flutamide was co-administered. In
      male rats prenatal testosterone increased blood urea nitrogen. In female rats
      flutamide increased creatinine clearance. In male rats prenatal testosterone and
      flutamide led to higher and lower, respectively, interstitial collagen deposition
      in adulthood. CONCLUSIONS: Prenatal testosterone induces proteinuria in
      adulthood. This effect is mediated via androgen receptor. Additional effects seem
      to be sex specific. Further studies should focus on the timing and dosing of
      testosterone as well as the applicability to human development.

PMID- 25577976
TI  - New challenges and structural modifications for Diagnostic and Interventional
      Imaging.

PMID- 25577975
TI  - A platelet-activating factor (PAF) receptor deficiency exacerbates diet-induced
      obesity but PAF/PAF receptor signaling does not contribute to the development of
      obesity-induced chronic inflammation.
AB  - Platelet-activating factor (PAF) is a well-known phospholipid that mediates acute
      inflammatory responses. In the present study, we investigated whether PAF/PAF
      receptor signaling contributed to chronic inflammation in the white adipose
      tissue (WAT) of PAF receptor-knockout (PAFR-KO) mice. Body and epididymal WAT
      weights were higher in PAFR-KO mice fed a high-fat diet (HFD) than in wild-type
      (WT) mice. TNF-alpha mRNA expression levels in epididymal WAT and the
      infiltration of CD11c-positive macrophages into epididymal WAT, which led to
      chronic inflammation, were also elevated in HFD-fed PAFR-KO mice. HFD-fed PAFR-KO
      mice had higher levels of fasting serum glucose than HFD-fed WT mice as well as
      impaired glucose tolerance. Although PAF receptor signaling up-regulated the
      expression of TNF-alpha and lipopolysaccharide induced the expression of acyl
      CoA:lysophosphatidylcholine acyltransferase 2 (LPCAT2) mRNA in bone marrow
      derived macrophages, no significant differences were observed in the expression
      of LPCAT2 mRNA and PAF levels in epididymal WAT between HFD-fed mice and normal
      diet-fed mice. In addition to our previous finding in which energy expenditure in
      PAF receptor (PAFR)-deficient mice was low due to impaired brown adipose tissue
      function, the present study demonstrated that PAF/PAF receptor signaling up
      regulated the expression of Ucp1 mRNA, which is essential for cellular
      thermogenesis, in 3T3-L1 adipocytes. We concluded that the marked accumulation of
      abdominal fat due to HFD feeding led to more severe chronic inflammation in WAT,
      which is associated with glucose metabolism disorders, in PAFR-KO mice than in WT
      mice, and PAF/PAF receptor signaling may regulate energy expenditure and
      adiposity. 

PMID- 25577977
TI  - Osteoarthritis and scapholunate instability in chondrocalcinosis.

PMID- 25577978
TI  - Mitochondrial DNA inheritance in the human fungal pathogen Cryptococcus gattii.
AB  - The inheritance of mitochondrial DNA (mtDNA) is predominantly uniparental in most
      sexual eukaryotes. In this study, we examined the mitochondrial inheritance
      pattern of Cryptococcus gattii, a basidiomycetous yeast responsible for the
      recent and ongoing outbreak of cryptococcal infections in the US Pacific
      Northwest and British Columbia (especially Vancouver Island) in Canada. Using
      molecular markers, we analyzed the inheritance of mtDNA in 14 crosses between
      strains within and between divergent lineages in C. gattii. Consistent with
      results from recent studies, our analyses identified significant variations in
      mtDNA inheritance patterns among strains and crosses, ranging from strictly
      uniparental to biparental. For two of the crosses that showed uniparental
      mitochondrial inheritance in standard laboratory conditions, we further
      investigated the effects of the following environmental variables on mtDNA
      inheritance: UV exposure, temperature, and treatments with the methylation
      inhibitor 5-aza-2'-deoxycytidine and with the ubiquitination inhibitor ammonium
      chloride. Interestingly, one of these crosses showed no response to these
      environmental variables while the other exhibited diverse patterns ranging from
      complete uniparental inheritance of the MATa parent mtDNA, to biparental
      inheritance, and to a significant bias toward inheritance of the MATalpha
      parental mtDNA. Our results indicate that mtDNA inheritance in C. gattii differs
      from that in its closely related species Cryptococcus neoformans. 

PMID- 25577980
TI  - Effects of microwaves (900 MHz) on peroxidase systems: A comparison between
      lactoperoxidase and horseradish peroxidase.
AB  - This work shows the effects of exposure to an electromagnetic field at 900 MHz on
      the catalytic activity of the enzymes lactoperoxidase (LPO) and horseradish
      peroxidase (HRP). Experimental evidence that irradiation causes conformational
      changes of the active sites and influences the formation and stability of the
      intermediate free radicals is documented by measurements of enzyme kinetics,
      circular dichroism spectroscopy (CD) and cyclic voltammetry. 

PMID- 25577979
TI  - Variations of glutamate concentration within synaptic cleft in the presence of
      electromagnetic fields: an artificial neural networks study.
AB  - Glutamate is an excitatory neurotransmitter that is released by the majority of
      central nervous system synapses and is involved in developmental processes,
      cognitive functions, learning and memory. Excessive elevated concentrations of
      Glu in synaptic cleft results in neural cell apoptosis which is called
      excitotoxicity causing neurodegenerative diseases. Hence, we investigated the
      possibility of extremely low frequency electromagnetic fields (ELF-EMF) as a risk
      factor which is able to change Glu concentration in synaptic clef. Synaptosomes
      as a model of nervous terminal were exposed to ELF-EMF for 15-55 min in flux
      intensity range from 0.1 to 2 mT and frequency range from 50 to 230 Hz. Finally,
      all raw data by INForm v4.02 software as an artificial neural network program was
      analyzed to predict the effect of whole mentioned range spectra. The results
      showed the tolerance of all effects between the ranges from -35 to +40 % compared
      to normal state when glutamatergic systems exposed to ELF-EMF. It indicates that
      glutamatergic system attempts to compensate environmental changes though release
      or reuptake in order to keep the system safe. Regarding to the wide range of ELF
      EMF acquired in this study, the obtained outcomes have potential for developing
      treatments based on ELF-EMF for some neurological diseases; however, in vivo
      experiments on the cross linking responses between glutamatergic and cholinergic
      systems in the presence of ELF-EMF would be needed.

PMID- 25577985
TI  - Identification of diverse circular single-stranded DNA viruses in adult
      dragonflies and damselflies (Insecta: Odonata) of Arizona and Oklahoma, USA.
AB  - Next generation sequencing and metagenomic approaches are commonly used for the
      identification of circular replication associated protein (Rep)-encoding single
      stranded (CRESS) DNA viruses circulating in various environments. These
      approaches have enabled the discovery of some CRESS DNA viruses associated with
      insects. In this study we identified and recovered 31 viral genomes which
      represent 24 distinct CRESS DNA viruses from seven dragonfly species
      (Rhionaeschna multicolor, Erythemis simplicicollis, Erythrodiplax fusca,
      Libellula quadrimaculata, Libellula saturata, Pachydiplax longipennis, and
      Pantala hymenaea) and two damselfly species (Ischnura posita, Ischnura ramburii)
      sampled in various locations in the states of Arizona and Oklahoma of the United
      States of America (USA). We also identified Sclerotinia sclerotiorum
      hypovirulence-associated DNA virus-1 (SsHADV-1) in P. hymenaea, E. simplicicollis
      and I. ramburii sampled in Oklahoma, which is the first report of SsHADV-1 in the
      New World. The genome architectures of the CRESS DNA viruses recovered vary, but
      they all have at least two major open reading frames (ORFs) that have either a
      bidirectional or unidirectional arrangement. Four of the viral genomes recovered,
      in addition to the three isolates of SsHADV-1, show similarities to viruses of
      the proposed gemycircularvirus group. Analysis of the Rep encoded by the
      remaining 24 viral genomes reveals that these are highly diverse and allude to
      the fact that they represent novel CRESS DNA viruses.

PMID- 25577986
TI  - Orientia tsutsugamushi, agent of scrub typhus, displays a single metapopulation
      with maintenance of ancestral haplotypes throughout continental South East Asia.
AB  - Orientia tsutsugamushi is the causative agent of scrub typhus, a major cause of
      febrile illness in rural area of Asia-Pacific region. A multi-locus sequence
      typing (MLST) analysis was performed on strains isolated from human patients from
      3 countries in Southeast Asia: Cambodia, Vietnam and Thailand. The phylogeny of
      the 56-kDa protein encoding gene was analyzed on the same strains and showed a
      structured topology with genetically distinct clusters. MLST analysis did not
      lead to the same conclusion. DNA polymorphism and phylogeny of individual gene
      loci indicated a significant level of recombination and genetic diversity whereas
      the ST distribution indicated the presence of isolated patches. No correlation
      was found with the geographic origin. This work suggests that weak divergence in
      core genome and ancestral haplotypes are maintained by permanent recombination in
      mites while the 56-kDa protein gene is diverging in higher speed due to selection
      by the mammalian immune system. 

PMID- 25577987
TI  - Genetic diversity of avian haemosporidians in Malaysia: cytochrome b lineages of
      the genera Plasmodium and Haemoproteus (Haemosporida) from Selangor.
AB  - The knowledge of the diversity of haemosporidian parasites is of primary
      importance as their representatives include agents of bird malaria. We
      investigated the occurrence of Haemoproteus spp. and Plasmodium spp. in bird
      populations from a single locality in the State of Selangor, Peninsular Malaysia,
      and report on the parasite prevalence of the two genera. A combination of methods
      (molecular and morphological) was used for detecting these parasites. Seventy
      nine bird individuals were caught using mist-nets in July and August 2010 at
      Gombak Field Station of the University of Malaya, Kuala Lumpur. In total, 23
      birds were identified as positive for Haemoproteus or Plasmodium infection and
      one individual was recognized as carrying mixed infection. The total prevalence
      of haemosporidians in the collected samples was 30.3%. Infections with parasites
      of the genus Haemoproteus were predominant compared to those of the genus
      Plasmodium. In total, 10 new cyt b lineages of Haemoproteus spp. and 3 new cyt b
      lineages of Plasmodium spp. were recorded in this study. From all recorded
      haemosporidian lineages (16 in total), 3 were known from previous studies -
      hCOLL2, hYWT2 and pNILSUN1. Two of them are linked with their corresponding
      morphospecies - Haemoproteus pallidus (COLL2) and Haemoproteus motacillae (YWT2).
      The morphological analysis in the present study confirmed the results obtained by
      the PCR method relative to prevalence, with 25.3% total prevalence of
      Haemoproteus and Plasmodium parasites. The intensities of infection varied
      between 0.01% and 19%. Most infections were light, with intensities below 0.1%.
      The present study is the first molecular survey of the protozoan blood parasites
      of the order Haemosporida recorded in Malaysia. 

PMID- 25577988
TI  - Assessment of emergency responders after a vinyl chloride release from a train
      derailment - New Jersey, 2012.
AB  - On November 30, 2012, at approximately 7:00 am, a freight train derailed near a
      small town in New Jersey. Four tank cars, including a breached tank car carrying
      vinyl chloride, landed in a tidal creek. Vinyl chloride, a colorless gas with a
      mild, sweet odor, is used in plastics manufacture. Acute exposure can cause
      respiratory irritation and headache, drowsiness, and dizziness; chronic
      occupational exposure can result in liver damage, accumulation of fat in the
      liver, and tumors (including angiosarcoma of the liver). Because health effects
      associated with acute exposures have not been well studied, the New Jersey
      Department of Health requested assistance from the Agency for Toxic Substances
      and Disease Registry (ATSDR) and CDC. On December 11, teams from these agencies
      deployed to assist the New Jersey Department of Health in conducting an
      assessment of exposures in the community as well as the occupational health and
      safety of emergency personnel who responded to the incident. This report
      describes the results of the investigation of emergency personnel. A survey of 93
      emergency responders found that 26% of respondents experienced headache and upper
      respiratory symptoms during the response. A minority (22%) reported using
      respiratory protection during the incident. Twenty-one (23%) of 92 respondents
      sought medical evaluation. Based on these findings, CDC recommended that response
      agencies 1) implement the Emergency Responder Health Monitoring and Surveillance
      (ERHMS) system for ongoing health monitoring of the emergency responders involved
      in the train derailment response and 2) ensure that in future incidents,
      respiratory protection is used when exposure levels are unknown or above the
      established occupational exposure limits. 

PMID- 25577989
TI  - Vital signs: alcohol poisoning deaths - United States, 2010-2012.
AB  - BACKGROUND: Alcohol poisoning is typically caused by binge drinking at high
      intensity (i.e., consuming a very large amount of alcohol during an episode of
      binge drinking). Approximately 38 million U.S. adults report binge drinking an
      average of four times per month and consuming an average of eight drinks per
      episode. METHODS: CDC analyzed data for 2010-2012 from the National Vital
      Statistics System to assess average annual alcohol poisoning deaths and death
      rates (ICD-10 codes X45 and Y15; underlying cause of death) in the United States
      among persons aged >=15 years, by sex, age group, race/ethnicity, and state.
      RESULTS: During 2010-2012, an annual average of 2,221 alcohol poisoning deaths
      (8.8 deaths per 1 million population) occurred among persons aged >=15 years in
      the United States. Of those deaths, 1,681 (75.7%) involved adults aged 35-64
      years, and 1,696 (76.4%) involved men. Although non-Hispanic whites accounted for
      the majority of alcohol poisoning deaths (67.5%; 1,500 deaths), the highest age
      adjusted death rate was among American Indians/Alaska Natives (49.1 per 1
      million). The age-adjusted rate of alcohol poisoning deaths in states ranged from
      5.3 per 1 million in Alabama to 46.5 per 1 million in Alaska. CONCLUSIONS: On
      average, six persons, mostly adult men, die from alcohol poisoning each day in
      the United States. Alcohol poisoning death rates vary substantially by state.
      IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Evidence-based strategies for preventing
      excessive drinking (e.g., regulating alcohol outlet density and preventing
      illegal alcohol sales in retail settings) could reduce alcohol poisoning deaths
      by reducing the prevalence, frequency, and intensity of binge drinking.

PMID- 25577990
TI  - Notes from the field: acute flaccid myelitis among persons aged <=21 years -
      United States, August 1-November 13, 2014.

PMID- 25577991
TI  - Notes from the field: occupationally acquired HIV infection among health care
      workers - United States, 1985-2013.

PMID- 25577992
TI  - Jinlida reduces insulin resistance and ameliorates liver oxidative stress in high
      fat fed rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Jinlida (JLD) is a compound preparation
      formulated on the basis of traditional Chinese medicine and is officially
      approved for the treatment of type 2 diabetes (T2DM) in China. We aimed to
      elucidate the mechanism of JLD treatment, in comparison to metformin treatment,
      on ameliorating insulin sensitivity in insulin resistant rats and to reveal its
      anti-oxidant properties. MATERIALS AND METHODS: Rats were fed with standard or
      high-fat diet for 6 weeks. After 6 weeks, the high-fat fed rats were subdivided
      into five groups and orally fed with JLD or metformin for 8 weeks. Fasting blood
      glucose (FBG), fasting blood insulin, blood lipid and antioxidant enzymes were
      measured. Intraperitoneal glucose tolerance test (IPGTT) and hyperinsulinemic
      euglycemic clamp technique were carried out to measure insulin sensitivity. Gene
      expression of the major signaling pathway molecules that regulate glucose uptake,
      including insulin receptor (INSR), insulin receptor substrate-1 (IRS-1),
      phosphoinositide-3-kinase (PI3K), protein kinase beta (AKT), and glucose
      transporter type 2 (GLUT2), were assessed by quantitative RT-PCR. The totle and
      phosphorylation expression of IRS-1, AKT, JNK and p38MAPK were determined by
      Western blot. RESULTS: Treatment with JLD effectively ameliorated the high-fat
      induced hyperglycemia, hyperinsulinemia and hyperlipidemia. Similar to metformin,
      the high insulin resistance in high-fat fed rats was significantly decreased by
      JLD treatment. JLD displayed anti-oxidant effects, coupled with up-regulation of
      the insulin signaling pathway. The attenuation of hepatic oxidative stress by JLD
      treatment was associated with reduced phosphorylation protein levels of JNK and
      p38MAPK. CONCLUSIONS: Treatment with JLD could moderate glucose and lipid
      metabolism as well as reduce hepatic oxidative stress, most likely through the
      JNK and p38MAPK pathways.

PMID- 25577993
TI  - This plant treats that illness? The hot-cold system and therapeutic procedures
      mediate medicinal plant use in San Miguel Tulancingo, Oaxaca, Mexico.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Understanding the reasoning behind the choice of
      medicinal plants is relevant for both pharmacological and ethnobotanical
      quantitative studies. In this study, we analyze how the traditional medical
      system influences the choice of medicinal plants in a Mexican indigenous
      population. MATERIALS AND METHODS: The study area was San Miguel Tulancingo,
      Oaxaca, Mexico, and the studied people the Rru ngigua (or Chocholtecs), an
      Otomangue group with only a few hundred speakers remaining. Through in-depth and
      repeated interviews of four traditional healers and ethnobotanical collections,
      we identified, described and classified the medicinal plants, the nosological
      units, the therapeutic procedures and the reasoning behind medicinal plant and
      treatment choice. RESULTS: The hot-cold system, which considers illness to be a
      result of humoral imbalance, strongly influences treatment choice. "Hot" plants
      are used mainly to treat "cold" diseases, and vice versa. With some variation,
      plants are selected mainly for this hot-or-cold property, and the specific plant
      species is often not very relevant. In addition, many plants are associated with
      specific healing procedures, such as sweat baths. The procedures, in turn, may be
      used to treat various diseases. CONCLUSIONS: The study shows that the
      relationship between medicinal plants and treated diseases is complex and
      indirect in most cases. It is strongly influenced by the hot-cold concept and by
      therapeutic procedures.

PMID- 25577994
TI  - Coblation endoscopic lingual lightening (CELL) for obstructive sleep apnea.
AB  - This study investigated the feasibility, safety and efficacy of Coblation
      endoscopic lingual lightening (CELL) surgery for obstructive sleep apnea (OSA).
      This study was a retrospective case series in a tertiary referral sleep center.
      Twenty-five adults with moderate to severe OSA and determined to have
      retropalatal and tongue base obstruction based on Friedman tongue position III
      and fiberoptic endoscopy underwent CELL in combination with modified
      uvulopalatopharyngoplasty, known as relocation pharyngoplasty. CELL involves
      transoral resection of tongue base muscle tissue and lingual tonsil using
      Coblation under endoscopic guidance. The mean operation time for CELL was 42.6 +/
      13.7 min. Total blood loss for CELL plus relocation pharyngoplasty was <50 ml in
      all patients. Mean postoperative pain score (sum of total pain scores/sum of
      total hospitalization day, visual analog scale, 0-10) was 2.6 +/- 0.6.
      Postoperative bleeding and taste disturbance extending beyond 3 months occurred
      in one patient (4 %) individually. No patients reported tongue weakness or speech
      dysfunction. Epworth sleepiness scale improved from 9.6 +/- 4.9 to 7.5 +/- 4.3 (p
      = 0.023). Apnea-hypopnea index decreased from 45.7 +/- 21.7 to 12.8 +/- 8.2
      events/hour (p < 0.001) 6 months after surgery. The overall response rate was 80
      %. CELL is feasible, safe and effective in treating tongue base obstruction in
      OSA patients who underwent simultaneous relocation pharyngoplasty.

PMID- 25577995
TI  - Audiological changes over time in adolescents and young adults with auditory
      neuropathy spectrum disorder.
AB  - Auditory neuropathy spectrum disorder (ANSD) describes a condition in which a
      patient's otoacoustic emissions (OAE) are (or were at one time) present and
      auditory brainstem responses (ABR) are abnormal or absent. ANSD is also diagnosed
      based on the presence of cochlear microphonics and abnormal or absent ABRs with
      or without abnormalities of OAE. We noted the changes in audiological
      characteristics over time with respect to pure tone thresholds, OAEs and Speech
      Identification Scores (SIS) in seven individuals with ANSD. The results indicated
      that all the individuals with ANSD had decreased SIS over time, whereas there was
      subsequent reduction in pure tone thresholds only in nine out of fourteen ears.
      There was absence of OAEs for two individuals in both ears during the follow-up
      evaluations. There was no regular pattern of changes in pure tone thresholds or
      SIS across all individuals. This indicates that there may be gradual worsening of
      hearing abilities in individuals with ANSD. Thus, regular follow-up and
      monitoring of audiological changes are necessary for individuals with ANSD. Also,
      longitudinal studies need to be done to further add evidence to the audiological
      changes over time in individuals with ANSD. 

PMID- 25577996
TI  - Potent anti-inflammatory effect of dioscin mediated by suppression of TNF-alpha
      induced VCAM-1, ICAM-1and EL expression via the NF-kappaB pathway.
AB  - The modulation of adhesion molecule expression and the reduction of aberrant
      leukocyte adhesion to the endothelium are attractive approaches for treating
      inflammation-related vascular complications, including atherosclerosis. Dioscin
      has a variety of biological activities including anti-inflammatory activity.
      However, the molecular mechanisms behind dioscin's anti-inflammatory effects are
      not fully understood. In this study, we investigated the molecular mechanism
      involved in the effects of dioscin on inflammatory mediators in tumor necrosis
      factor-alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells
      (HUVECs). In vitro, dioscin decreased monocyte adhesion to TNF-alpha-treated
      HUVECs by reducing vascular cell adhesion molecule-1 (VCAM-1) and intercellular
      adhesion molecule 1 (ICAM-1) expression and inhibiting endothelial lipase (EL)
      expression in TNF-alpha-treated HUVECs and macrophages by blocking the nuclear
      factor-kappaB (NF-kappaB) pathway. Thus, dioscin might inhibit inflammation by
      interrupting the NF-kappaB signaling pathway and could potentially contribute to
      treatments for inflammatory diseases and atherosclerosis. 

PMID- 25577997
TI  - Morin, a dietary flavonoid, exhibits anti-fibrotic effect and induces apoptosis
      of activated hepatic stellate cells by suppressing canonical NF-kappaB signaling.
AB  - In experimental liver fibrosis, activated hepatic stellate cells (HSCs) play a
      central role and thus, induction of apoptosis of activated HSCs is a promising
      therapeutic strategy for liver fibrosis. The present study was designed to
      elucidate the molecular mechanisms of the pro-apoptotic effects of morin, a
      dietary flavonoid, in vitro and in vivo. Culture-activated human HSCs (LX-2
      cells) were treated with morin (50 MUM) for 24 and 48 h, and the mechanism of
      cell death induced by morin was evaluated. Also, the anti-fibrotic and pro
      apoptotic effect of morin in diethylnitrosamine (DEN)-induced fibrotic rats were
      determined. Morin induced apoptosis in cultured LX-2 cells by preventing the
      nuclear translocation of nuclear factor-kappaBp65 (NF-kappaBp65) by inhibiting NF
      kappaB activation via inhibition of IkappaBalpha degradation and thereby
      suppressing anti-apoptotic proteins and activating caspases. In fibrotic rats,
      morin treatment resulted in inhibition of canonical NF-kappaB signaling and
      induction of apoptosis, mainly by downregulating Bcl-2, upregulating Bax and cyt
      c and by activation of caspase-9 and caspase-3. Translocation of
      phosphatidylserine to the outer membrane, altered nuclear morphology and DNA
      fragmentation confirmed the induction of apoptosis by morin. Overall, morin
      treatment ameliorated experimental liver fibrosis, most likely through induction
      of apoptosis by inhibiting canonical NF-kappaB signaling in activated HSCs. It is
      therefore postulated that morin is a potential therapeutic candidate for liver
      fibrosis. 

PMID- 25577998
TI  - The journal Adicciones: continuity and innovation.

PMID- 25577999
TI  - [Mediating role of emotional regulation between impulsive behavior in gambling,
      Internet and videogame abuse, and dysfunctional symptomatology in young adults
      and adolescents].
AB  - The way emotions are regulated might affect the engagement on risk behaviors in
      adolescents and young adults. Therefore, studying the relationship between these
      variables could be of great importance. Some of the less studied risky behaviors
      are pathological gambling, and Internet and videogame abuse. This research aims
      to analyze the existing relationship between such risky behaviors, emotion
      regulation, and dysfunctional psychological symptomatology (depression, anxiety,
      phobic anxiety, somatization, obsessive-?compulsive behavior, interpersonal
      sensitivity, hostility, paranoid ideation, and psychoticism). In addition, it
      also looks to assess whether emotional regulation plays a mediating role between
      pathological gambling, and Internet and videogame abuse, and psychological
      symptomatology. The sample was composed of 1312 young adults and adolescents,
      aged between 12 and 30, recruited from scholar centers, universities and free
      time groups, and from associations and centers associated with FEJAR (Spanish
      Federation of Rehabilitated Gamblers). Participants completed measurements of
      impulsive behavior, emotion regulation, and dysfunctional symptomatology. Results
      showed that there is generally a positive and significant relation between these
      variables. Moreover, it has been pointed out that emotion regulation mediates the
      association between impulsive behavior and dysfunctional symptomatology among
      those young adults and adolescents who engage in these impulsive behaviors,
      except for the relation between videogame abuse and depressive symptomatology.
      Training in emotional regulation skills could be useful in dealing with and
      treating this type of behaviors in adolescents and young adults.

PMID- 25578000
TI  - [Validity evidence of the Alcohol, Smoking and Substance Involvement Screening
      Test (ASSIST) in Chile].
AB  - This study aims to psychometrically validate the Chilean version of the Alcohol,
      Smoking and Substance Involvement Screening Test ASSIST. Specifically, this study
      is interested in evaluating the reliability, consistency and concurrent and
      discriminant validity of this instrument. The sample was composed for a total of
      400 people from four different settings: treatment centers (residential and
      ambulatories), primary health care, police stations and companies. The
      reliability of the ASSIST was high (&#945; = .86 for Alcohol, &#945; = .84 for
      marijuana and &#945; = .90 for cocaine). The intra class correlation coefficient
      (ICC) with test-retest comparison was statistically significant for Alcohol (ICC
      = .66), marijuana (ICC = .74) and cocaine (ICC = .80). There were statistically
      significant correlations between the ASSIST and the AUDIT score (Pearson?s r =
      .85), the ASSIST and the ASI-Lite score (r between .66 and .83 for tobacco,
      alcohol, marijuana and cocaine), and the ASSIST and the SDS score (r = .65). The
      original cutoff point for high risk detection was 27 points, however, in order to
      have a better balance between sensitivity and specificity the cut was changed to
      21 points. The ASSIST presents good psychometric properties and therefore is a
      reliable and valid instrument to be used as a mechanism to detect risk levels of
      substance use in the Chilean population. 

PMID- 25578001
TI  - [The Questionnaire of Experiences Associated with Video games (CERV): an
      instrument to detect the problematic use of video games in Spanish adolescents].
AB  - The aim of this study is to validate the Video Game-Related Experiences
      Questionnaire (CERV in Spanish). The questionnaire consists of 17 items,
      developed from the CERI (Internet-Related Experiences Questionnaire - Beranuy and
      cols.), and assesses the problematic use of non-massive video games. It was
      validated for adolescents in Compulsory Secondary Education. To validate the
      questionnaire, a confirmatory factor analysis (CFA) and an internal consistency
      analysis were carried out. The factor structure shows two factors: (a)
      Psychological dependence and use for evasion; and (b) Negative consequences of
      using video games. Two cut-off points were established for people with no
      problems in their use of video games (NP), with potential problems in their use
      of video games (PP), and with serious problems in their use of video games (SP).
      Results show that there is higher prevalence among males and that problematic use
      decreases with age. The CERV seems to be a good instrument for the screening of
      adolescents with difficulties deriving from video game use. Further research
      should relate problematic video game use with difficulties in other life domains,
      such as the academic field. 

PMID- 25578002
TI  - Workaholism in Brazil: measurement and individual differences.
AB  - The aim of this research is the measurement and assessment of individual
      differences of workaholism in Brazil, an important issue which affects the
      competitiveness of companies. The WART 15-PBV was applied to a sample of 153
      managers from companies located in Brazil, 82 (53.6%) women and 71 (46.4%) men.
      Ages ranged from 20 to 69 years with an average value of 41 (SD=9.06). We
      analyzed, on one hand, the factor structure of the questionnaire, its internal
      consistency and convergent (with the Dutch Work Addiction Scale - DUWAS) and
      criterion validity (with General Health Questionnaire ? GHQ). On the other hand,
      we analyzed individual gender differences on workaholism. WART15-PBV has good
      psychometric properties, and evidence for convergent and criterion validity.
      Females and males differed on Impaired Communication / Self-Absorption dimension.
      This dimension has a direct effect only on men?s health perception, while
      Compulsive tendencies dimension has a direct effect for both genders. The
      findings suggest the WART15-PBV is a valid measure of workaholism that would
      contribute to the workers? health and their professional and personal life, in
      order to encourage adequate conditions in the workplace taking into account
      workers? individual differences. 

PMID- 25578003
TI  - [Neurocognitive anomalies associated with the binge drinking pattern of alcohol
      consumption in adolescents and young people: a review].
AB  - Binge drinking (BD) is the most common problematic drinking pattern during
      adolescence and youth. At the same time, it is a period marked by profound
      structural and functional brain changes, which may be affected by heavy alcohol
      consumption. In recent years, a considerable number of studies that attempt to
      characterize the effects of BD on the brain has been published. However, to date
      there is not any critical review in Spanish language on neurostructural,
      neurophysiological and cognitive consequences that may result from the
      maintenance of a BD pattern of alcohol consumption during adolescence and youth.
      The purpose of this review is to critically summarize the main research results
      on the effects of BD on the brain. To this end, a literature search in databases
      Web of Knowledge, PubMed and PsycINFO for the period 2000-2013 was performed. In
      general, studies agree that BD is associated with 1) lower performance on tasks
      assessing cognitive processes such as attention, memory and executive functions,
      2) structural changes (in white matter and gray matter) in different brain
      regions and 3) neurophysiological abnormalities (hyper/hypoactivation) linked to
      different cognitive processes. These results, although still need to be
      contrasted, warn about important consequences that could result from the
      persistence of BD on a young and still maturing brain. 

PMID- 25578004
TI  - Neurobiological alterations in alcohol addiction: a review.
AB  - The exact mechanism by which ethanol exerts its effects on the brain is still
      unknown. However, nowadays it is well known that ethanol interacts with specific
      neuronal membrane proteins involved in signal transmission, resulting in changes
      in neural activity. In this review different neurochemical alterations produced
      by ethanol are described. Primarily, ethanol interacts with two membrane
      receptors: GABAA and NMDA ion channel receptors. Ethanol enhances the GABA action
      and antagonizes glutamate action, therefore acting as a CNS depressant. In
      addition, ethanol affects most other neurochemical and endocrine systems. In
      regard to the brain reward system, both dopaminergic and opioid system are
      affected by this drug. Furthermore, the serotonergic, noradrenergic,
      corticotropin-releasing factor and cannabinoid systems seem to play an important
      role in the neurobiology of alcoholism. At last but not least, ethanol can also
      modulate cytoplasmic components, including the second messengers. We also review
      briefly the different actual and putative pharmacological treatments for
      alcoholism, based on the alterations produced by this drug.

PMID- 25578005
TI  - The importance of socio-legal interventions in the case management of a severe
      dual-pathology program: our 6 years?' experience.

PMID- 25578009
TI  - Synergy of elastic and inelastic energy loss on ion track formation in SrTiO3.
AB  - While the interaction of energetic ions with solids is well known to result in
      inelastic energy loss to electrons and elastic energy loss to atomic nuclei in
      the solid, the coupled effects of these energy losses on defect production,
      nanostructure evolution and phase transformations in ionic and covalently bonded
      materials are complex and not well understood due to dependencies on electron
      electron scattering processes, electron-phonon coupling, localized electronic
      excitations, diffusivity of charged defects, and solid-state radiolysis. Here we
      show that a colossal synergy occurs between inelastic energy loss and pre
      existing atomic defects created by elastic energy loss in single crystal
      strontium titanate (SrTiO3), resulting in the formation of nanometer-sized
      amorphous tracks, but only in the narrow region with pre-existing defects. These
      defects locally decrease the electronic and atomic thermal conductivities and
      increase electron-phonon coupling, which locally increase the intensity of the
      thermal spike for each ion. This work identifies a major gap in understanding on
      the role of defects in electronic energy dissipation and electron-phonon
      coupling; it also provides insights for creating novel interfaces and
      nanostructures to functionalize thin film structures, including tunable
      electronic, ionic, magnetic and optical properties.

PMID- 25578023
TI  - Axl inhibition: a potential road to a novel acute myeloid leukemia therapy?
AB  - Novel treatment options in acute myeloid leukemia (AML) are urgently needed;
      treatment has not changed significantly over the past decades and survival is
      still dismal, especially in elderly patients. Axl, a member of the Tyro3, Axl,
      Mer (TAM) receptor family, mediates proliferation and survival of AML cells and
      is upregulated upon cytostatic treatment. In addition, AML cells induce
      expression of the Axl ligand growth arrest-specific gene 6 (Gas6) in bone marrow
      stroma cells, which further amplifies their growth and therapy resistance.
      Interruption of Axl signaling by pharmacological approaches, including the small
      molecule Axl inhibitor BGB324, decreased disease burden and prolonged survival of
      AML mice. The Gas6-Axl pathway has translational relevance because Axl is
      expressed by approximately 50% of AML patients and Axl-targeting approaches can
      block growth of primary human AML cells. Thus, Axl represents a potential novel
      target in AML and BGB324 is now in clinical development. 

PMID- 25578024
TI  - Mapping the results of local statistics: Using geographically weighted
      regression.
AB  - The application of geographically weighted regression (GWR) - a local spatial
      statistical technique used to test for spatial nonstationarity - has grown
      rapidly in the social, health and demographic sciences. GWR is a useful
      exploratory analytical tool that generates a set of location-specific parameter
      estimates which can be mapped and analysed to provide information on spatial
      nonstationarity in relationships between predictors and the outcome variable. A
      major challenge to GWR users, however, is how best to map these parameter
      estimates. This paper introduces a simple mapping technique that combines local
      parameter estimates and local t-values on one map. The resultant map can
      facilitate the exploration and interpretation of nonstationarity.

PMID- 25578025
TI  - N, S co-doped graphene quantum dots from a single source precursor used for
      photodynamic cancer therapy under two-photon excitation.
AB  - Using polythiophene derivatives as single source precursors, nitrogen (N) and
      sulfur (S) co-doped graphene quantum dots (NS-GQD) were prepared. Under two
      photon excitation (800 nm), the NS-GQD exhibited excellent photostability and
      high (1)O2 generation, and therefore were developed as photodynamic therapy
      agents for cancer treatment. 

PMID- 25578017
TI  - Omega-3 polyunsaturated fatty acids as an angelus custos to rescue patients from
      NSAID-induced gastroduodenal damage.
AB  - Nonsteroidal anti-inflammat ory drugs (NSAIDs) are one of the drug types
      frequently prescribed for their analgesic, anti-inflammatory, and antithrombotic
      actions, but carry a risk of major gastroduodenal damage from mild erosive
      changes to serious ulceration leading to fatal outcomes. From the long history of
      willow tree bark and its extracts being applied for the relief of pain and fever,
      the synthesis of acetylsalicylic acid, the development of selective
      cyclooxygenase 2 inhibitors (coxibs), and the identification of a G-protein
      coupled receptor for prostaglandin, the popular combination regimen of an NSAID
      and a proton pump inhibitor was invented, but development was continued for
      further improvement. With regard to major NSAID adverse effects, gastrointestinal
      (GI) and cardiovascular (CV) risks still remained as problems to be solved. In
      this review, it is shown that n-3 polyunsaturated fatty acid (PUFA) based NSAIDs
      can be an angelus custos, supported with facts that an intake of essential n-3
      PUFAs orchestrates concerted protective actions against two notorious side
      effects of NSAIDs, the aforementioned GI risk and CV risk of NSAIDs. Since pills
      containing n-3 PUFAs, omega-3-acid ethyl ester capsules (Lovaza, Omarcor), have
      already been safely prescribed to prevent atherosclerosis through lessening lipid
      burdening, the introduction of a drug delivery system such as a gastroretentive
      form of n-3 PUFA based NSAIDs will highlight newer hope for GI safety under the
      guarantee of reduced CV risk. Because n-3 PUFAs have been proven to attenuate
      cytotoxicity, inhibit lipid-raft-associated harmful signaling, and relieve
      oxidative stress relevant to NSAIDs, n-3 PUFA based NSAIDs will be next
      generation GI-safe NSAIDs. 

PMID- 25578026
TI  - Molecular interfaces for plasmonic hot electron photovoltaics.
AB  - The use of self-assembled monolayers (SAMs) to improve and tailor the
      photovoltaic performance of plasmonic hot-electron Schottky solar cells is
      presented. SAMs allow the simultaneous control of open-circuit voltage, hot
      electron injection and short-circuit current. To that end, a plurality of
      molecule structural parameters can be adjusted: SAM molecule's length can be
      adjusted to control plasmonic hot electron injection. Modifying SAMs dipole
      moment allows for a precise tuning of the open-circuit voltage. The
      functionalization of the SAM can also be selected to modify short-circuit
      current. This allows the simultaneous achievement of high open-circuit voltages
      (0.56 V) and fill-factors (0.58), IPCE above 5% at the plasmon resonance and
      maximum power-conversion efficiencies of 0.11%, record for this class of devices.

PMID- 25578030
TI  - Enhanced removal performance of arsenate and arsenite by magnetic graphene oxide
      with high iron oxide loading.
AB  - Magnetic iron oxide/graphene oxide (MGO) with high iron loading (51 wt%) has been
      successfully synthesized using the co-precipitation method, and then used as
      adsorbents for the removal of arsenate and arsenite from aqueous solutions. The
      resulting MGO possesses desirable magnetic properties (12.8 emu g(-1)) and
      excellent adsorption properties for the removal of As(III) and As(IV) with
      significantly enhanced adsorption capacities of 54.18 mg g(-1) and 26.76 mg g(
      1), respectively. These values are much higher than those of other GO-based
      composites reported previously. The kinetic, equilibrium and environmental
      effects (pH, ionic strength, coexist anion) of MGO were obtained experimentally.
      A synchrotron-based X-ray fluorescent microprobe was used to generate elemental
      distribution maps of adsorbents; the results suggest that As(v) became
      preferentially associated with iron oxides during the adsorption process, and
      that the distribution of Fe is directly correlated with the distribution of As.

PMID- 25578031
TI  - Recombination is a key driver of genomic and phenotypic diversity in a
      Pseudomonas aeruginosa population during cystic fibrosis infection.
AB  - The Cystic Fibrosis (CF) lung harbors a complex, polymicrobial ecosystem, in
      which Pseudomonas aeruginosa is capable of sustaining chronic infections, which
      are highly resistant to multiple antibiotics. Here, we investigate the phenotypic
      and genotypic diversity of 44 morphologically identical P. aeruginosa isolates
      taken from a single CF patient sputum sample. Comprehensive phenotypic analysis
      of isolates revealed large variances and trade-offs in growth, virulence factors
      and quorum sensing (QS) signals. Whole genome analysis of 22 isolates revealed
      high levels of intra-isolate diversity ranging from 5 to 64 SNPs and that
      recombination and not spontaneous mutation was the dominant driver of diversity
      in this population. Furthermore, phenotypic differences between isolates were not
      linked to mutations in known genes but were statistically associated with
      distinct recombination events. We also assessed antibiotic susceptibility of all
      isolates. Resistance to antibiotics significantly increased when multiple
      isolates were mixed together. Our results highlight the significant role of
      recombination in generating phenotypic and genetic diversification during in vivo
      chronic CF infection. We also discuss (i) how these findings could influence how
      patient-to-patient transmission studies are performed using whole genome
      sequencing, and (ii) the need to refine antibiotic susceptibility testing in
      sputum samples taken from patients with CF. 

PMID- 25578034
TI  - The role of the cerebellum in multiple sclerosis.
AB  - In multiple sclerosis (MS), cerebellar signs and symptoms as well as cognitive
      dysfunction are frequent and contribute to clinical disability with only poor
      response to symptomatic treatment. The current consensus paper highlights the
      broad range of clinical signs and symptoms of MS patients, which relate to
      cerebellar dysfunction. There is considerable evidence of cerebellar involvement
      in MS based on clinical, histopathological as well as structural and functional
      magnetic resonance imaging (MRI) studies. The review of the recent literature,
      however, also demonstrates a high variability of results. These discrepancies
      are, at least partially, caused by the use of different techniques and
      substantial heterogeneity among the patient cohorts in terms of disease duration,
      number of patients, and progressive vs. relapsing disease courses. Moreover, the
      majority of studies were cross-sectional, providing little insight into the
      dynamics of cerebellar involvement in MS. Some links between the
      histopathological changes, the structural and functional abnormalities as
      captured by MRI, cerebellar dysfunction, and the clinical consequences are
      starting to emerge and warrant further study. A consensus is formed that this
      line of research will benefit from advances in neuroimaging techniques that allow
      to trace cerebellar involvement at higher resolution. Using a prospective study
      design, multimodal high-resolution cerebellar imaging is highly promising,
      particularly in patients who present with radiologically or clinically isolated
      syndromes or newly diagnosed MS. 

PMID- 25578035
TI  - Asymmetries in Cerebellar Plasticity and Motor Learning.
AB  - Synaptic plasticity at the parallel fiber to Purkinje cell synapse has long been
      considered a cellular correlate for cerebellar motor learning. Functionally, long
      term depression and long-term potentiation at these synapses seem to be the
      reverse of each other, with both pre- and post-synaptic expression occurring in
      both. However, different cerebellar motor learning paradigms have been shown to
      be asymmetric and not equally reversible. Here, we discuss the asymmetric
      reversibility shown in the vestibulo-ocular reflex and eyeblink conditioning and
      suggest that different cellular plasticity mechanisms might be recruited under
      different conditions leading to unequal reversibility. 

PMID- 25578037
TI  - Targeting histone lysine methylation in cancer.
AB  - Within the vast landscape of histone modifications lysine methylation has gained
      increasing attention because of its profound regulatory potential. The
      methylation of lysine residues on histone proteins modulates chromatin structure
      and thereby contributes to the regulation of DNA-based nuclear processes such as
      transcription, replication and repair. Protein families with opposing catalytic
      activities, lysine methyltransferases (KMTs) and demethylases (KDMs), dynamically
      control levels of histone lysine methylation and individual enzymes within these
      families have become candidate oncology targets in recent years. A number of high
      quality small molecule inhibitors of these enzymes have been identified. Several
      of these compounds elicit selective cancer cell killing in vitro and robust
      efficacy in vivo, suggesting that targeting 'histone lysine methylation pathways'
      may be a relevant, emerging cancer therapeutic strategy. Here, we discuss
      individual histone lysine methylation pathway targets, the properties of
      currently available small molecule inhibitors and their application in the
      context of cancer.

PMID- 25578038
TI  - Liquid crystal seed nucleates liquid-solid phase change in ceria nanoparticles.
AB  - Molecular dynamics (MD) simulation was used to explore the liquid-solid (crystal)
      phase change of a ceria nanoparticle. The simulations reveal that the crystalline
      seed, which spontaneously evolves and nucleates crystallisation, is a liquid
      rather than a solid. Evidence supporting this concept includes: (a) only 3% of
      the total latent heat of solidification had been liberated after 25% of the
      nanoparticle had (visibly) crystallised. (b) Cerium ions, comprising the (liquid)
      crystal seed had the same mobility as cerium ions comprising the amorphous
      regions. (c) Cerium ion mobility only started to reduce (indicative of
      solidification) after 25% of the nanoparticle had crystallised. (d) Calculated
      radial distribution functions (RDF) revealed no long-range structure when 25% of
      the nanoparticle had (visibly) crystallised. We present evidence that the concept
      of a liquid crystal seed is more general phenomenon rather than applicable only
      to nanoceria. 

PMID- 25578039
TI  - Effect of individual protective behaviors on influenza transmission: an agent
      based model.
AB  - It is well established in the epidemiological literature that individual
      behaviors have a significant effect on the spread of infectious diseases. Agent
      based models are increasingly being recognized as the next generation of
      epidemiological models. In this research, we use the ability of agent-based
      models to incorporate behavior into simulations by examining the relative
      importance of vaccination and social distancing, two common measures for
      controlling the spread of infectious diseases, with respect to seasonal
      influenza. We modeled health behaviour using the result of a Health Belief Model
      study focused on influenza. We considered a control and a treatment group to
      explore the effect of education on people's health-related behaviors patterns.
      The control group reflects the behavioral patterns of students based on their
      general knowledge of influenza and its interventions while the treatment group
      illustrates the level of behavioral changes after individuals have been educated
      by a health care expert. The results of this study indicate that self-initiated
      behaviors are successful in controlling an outbreak in a high contact rate
      location such as a university. Self-initiated behaviors resulted in a population
      attack rate decrease of 17% and a 25% reduction in the peak number of cases. The
      simulation also provides significant evidence for the effect of an HBM theory
      based educational program to increase the rate of applying the target
      interventions (vaccination by 22% percent and social distancing by 41%) and
      consequently to control the outbreak.

PMID- 25578036
TI  - Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms.
AB  - The cerebellum is an important target of ethanol toxicity given that cerebellar
      ataxia is the most consistent physical manifestation of acute ethanol
      consumption. Despite the significance of the cerebellum in ethanol-induced
      cerebellar ataxia (EICA), the cellular and molecular mechanisms underlying EICA
      are incompletely understood. However, two important findings have shed greater
      light on this phenomenon. First, ethanol-induced blockade of cerebellar adenosine
      uptake in rodent models points to a role for adenosinergic A1 modulation of EICA.
      Second, the consistent observation that intracerebellar administration of
      nicotine in mice leads to antagonism of EICA provides evidence for a critical
      role of cerebellar nitric oxide (NO) in EICA reversal. Based on these two
      important findings, this review discusses the potential molecular events at two
      key synaptic sites (mossy fiber-granule cell-Golgi cell (MGG synaptic site) and
      granule cell parallel fiber-Purkinje cell (GPP synaptic site) that lead to EICA.
      Specifically, ethanol-induced neuronal NOS inhibition at the MGG synaptic site
      acts as a critical trigger for Golgi cell activation which leads to granule cell
      deafferentation. Concurrently, ethanol-induced inhibition of adenosine uptake at
      the GPP synaptic site produces adenosine accumulation which decreases glutamate
      release and leads to the profound activation of Purkinje cells (PCs). These
      molecular events at the MGG and GPP synaptic sites are mutually reinforcing and
      lead to cerebellar dysfunction, decreased excitatory output of deep cerebellar
      nuclei, and EICA. The critical importance of PCs as the sole output of the
      cerebellar cortex suggests normalization of PC function could have important
      therapeutic implications. 

PMID- 25578040
TI  - Effects of anthocyans on the expression of organic anion transporting
      polypeptides (SLCOs/OATPs) in primary human hepatocytes.
AB  - Anthocyans (anthocyanins and their aglycones anthocyanidins) are colorful
      pigments, naturally occurring in fruits. They exhibit many biological effects and
      have potent health benefits. Anthocyans are widely used as dietary supplements
      and the safety of products containing them is of great importance. To investigate
      whether anthocyans influence the expression of hepatic uptake transporters from
      the organic anion transporting polypeptide (SLCO gene/OATP protein) family, we
      carried out studies on primary cultures of human hepatocytes. The hepato-cellular
      accumulation of widely used drugs such as statins and some anticancer drugs is
      mediated by the liver-specific OATP1B1 and OATP1B3, thus any interference with
      expression of these particular transporters might influence therapeutic outcomes.
      We evaluated the effects of 21 anthocyanins and their corresponding 6
      anthocyanidins on the expression levels of SLCO1B1/SLCO1B3 by RT-qPCR. Changes in
      OATP protein levels were confirmed by western blotting. Our data show that
      OATP1B1 responds differently to anthocyans compared with OATP1B3. We observed the
      induction of SLCO1B1 gene and OATP1B1 protein in four hepatocyte samples by the
      anthocyanins malvin chloride, malvidin-3-O-galactoside chloride and cyanidin-3-O
      sophoroside chloride. For SLCO1B3, a reduction in the expression levels was seen
      with delphin chloride and the anthocyanidin pelargonidin. Although the values
      varied considerably between primary hepatocyte isolates from different
      individuals, a mean induction of SLCO1B1 (up to 60%) and reduction of SLCO1B3 (by
      less than 25%) were detected. We propose that the effects of anthocyans derived
      from high dose dietary supplements may have to be taken into account in patients
      undergoing a therapy with drugs transported by OATP1B1 and OATP1B3. 

PMID- 25578041
TI  - Pan-PI-3 kinase inhibitor SF1126 shows antitumor and antiangiogenic activity in
      renal cell carcinoma.
AB  - PURPOSE: SF1126 is a vascular-targeted pan-PI-3K inhibitor prodrug with antitumor
      and antiangiogenic activity and has completed phase I clinical trial in solid
      tumors and B-cell malignancies. In this study, we investigated the effect of
      SF1126 on hypoxic HIF-1alpha/HIF-2alpha stability as well as on antitumor and/or
      antiangiogenic activity in renal cell carcinoma (RCC) models in vitro and in
      vivo. METHODS: The effect of SF1126 on hypoxic HIF-1alpha/HIF-2alpha protein
      stability, antitumor and antiangiogenic activity was studied on VHL-null (786-0)
      and VHL-WT (Caki) RCC cells. RESULTS: Our data demonstrate that SF1126 treatment
      abrogates the stabilization of HIF-2alpha in 786-0 (VHL-mutated) RCC cell line
      under normoxic and hypoxic conditions. Similarly, hypoxic stabilization of HIF
      1alpha and its activity were also suppressed following SF1126 treatment in Caki
      cell line (VHL-WT). Herein, we provide mechanistic evidence that HIF-2alpha can
      be degraded in cytoplasm under hypoxic conditions via the 26S proteasome and that
      MDM2 is the E3 ligase which induces the hypoxic degradation of HIF-2alpha in PI
      3K-dependent manner in VHL-deficient RCC cells. Moreover, SF1126 administered to
      RCC-xenografted mice at 25 mg/kg/dose subcutaneously three times per week for 3
      weeks results in marked inhibition of tumor growth (>90 % inhibition) (P < 0.05).
      Consistent with SF1126 treatment's effects on HIF-1alpha/HIF-2alpha, microvessel
      density analysis of Caki and 786-0 tumor tissues demonstrated that SF1126 has
      potent antiangiogenic activity in vivo. Finally, SF1126 caused a profound
      inhibition of integrin-mediated migration and blocked the integrin-induced
      conversion of GDP-Rac1 to its GTP-bound active state. CONCLUSIONS: These results
      validate the in vivo efficacy of SF1126 as a clinically viable antiangiogenic,
      pan-PI-3K inhibitor prodrug for phase II clinical trials in the treatment of RCC.

PMID- 25578042
TI  - Template-free TiO2 hollow submicrospheres embedded with SnO2 nanobeans as a
      versatile scattering layer for dye-sensitized solar cells.
AB  - Nanobean SnO2-embedded TiO2 hollow submicrospheres are presented as a scattering
      layer for the first time in dye-sensitized solar cells. This designed mesoporous
      submicrostructure simultaneously promotes dye adsorption, light harvesting, and
      electron transport, leading to 28% improvement in the conversion efficiency
      compared to film-based SnO2. 

PMID- 25578043
TI  - 1.1 MUm superficially porous particles for liquid chromatography: part II: column
      packing and chromatographic performance.
AB  - The predicted advantages of superficially porous particles over totally porous
      particles are decreased eddy dispersion, longitudinal diffusion, and resistance
      to mass transfer contributions to the theoretical plate height. While sub-2
      micron superficially porous particles are commercially available, further
      improvements in performance are predicted by decreasing the particle diameter and
      decreasing the porous layer thickness. 1.1 MUm superficially porous particles
      with 187A pores have been synthesized using a layer-by-layer method tuned for
      production of smaller diameter particles. Following synthesis, these particles
      were packed into 30 MUm i.d. capillary columns and their chromatographic
      performance evaluated using electrochemical detection. Based on the initial
      studies, the column efficiency did not meet theory, but was similar to the
      commercially available products tested. It is believed that the column packing
      process plays a critical role in the sub-par column performance. To determine if
      column efficiency could be predicted by solvent-particle interactions, in
      solution optical microscopy and sedimentation velocity of particles in various
      slurry solvents were investigated and compared to column performance. Aggregating
      slurry solvents, such as methanol were found to produce columns with increased
      efficiency. The hmin for a column packed with an acetone slurry and a methanol
      slurry at 3mg/mL were found to be 6.3 and 3.5, respectively. Increasing the
      slurry concentration to 25mg/mL further improved the efficiency, producing a
      column with an hmin of 2.6. These efficiency results were accurately predicted by
      in-solution optical microscopy.

PMID- 25578044
TI  - Comprehensive two-dimensional liquid chromatography coupled to high resolution
      time of flight mass spectrometry for chemical characterization of sewage
      treatment plant effluents.
AB  - For the first time a comprehensive two-dimensional liquid chromatography (LC*LC)
      system coupled with a high resolution time-of-flight mass spectrometer (HR-ToF
      MS) was developed and applied for analysis of emerging toxicants in wastewater
      effluent. The system was optimized and validated using environmental standard
      compound mixtures of e.g. carbamate pesticides and polycyclic aromatic
      hydrocarbons (PAHs), to characterize the chromatographic system, to test the
      stability of the retention times and orthogonality. Various stationary phases in
      the second dimension were compared for the LC*LC analysis of silicon rubber
      passive sampler extracts of a wastewater effluent. A combination of C18 and
      Pentafluorophenyl (PFP) was found to be most effective. Finally, the hyphenation
      of LC*LC with HR-ToF MS was optimized, including splitter settings, transfer of
      data files between the different software packages and background subtraction
      using instrument software tools, after which tentative identification of 20
      environmental contaminants was achieved, including pesticides, pharmaceuticals
      and food additives. As examples, three pesticides (isoproturon, terbutryn and
      diazinon) were confirmed by two-dimensional retention alignment.

PMID- 25578045
TI  - Polysaccharide characterization by hollow-fiber flow field-flow fractionation
      with on-line multi-angle static light scattering and differential refractometry.
AB  - Accurate characterization of the molar mass and size of polysaccharides is an
      ongoing challenge, oftentimes due to architectural diversity but also to the
      broad molar mass (M) range over which a single polysaccharide can exist and to
      the ultra-high M of many polysaccharides. Because of the latter, many of these
      biomacromolecules experience on-column, flow-induced degradation during analysis
      by size-exclusion and, even, hydrodynamic chromatography (SEC and HDC,
      respectively). The necessity for gentler fractionation methods has, to date, been
      addressed employing asymmetric flow field-flow fractionation (AF4). Here, we
      introduce the coupling of hollow-fiber flow field-flow fractionation (HF5) to
      multi-angle static light scattering (MALS) and differential refractometry (DRI)
      detection for the analysis of polysaccharides. In HF5, less stresses are placed
      on the macromolecules during separation than in SEC or HDC, and HF5 can offer a
      higher sensitivity, with less propensity for system overloading and analyte
      aggregation, than generally found in AF4. The coupling to MALS and DRI affords
      the determination of absolute, calibration-curve-independent molar mass averages
      and dispersities. Results from the present HF5/MALS/DRI experiments with
      dextrans, pullulans, and larch arabinogalactan were augmented with hydrodynamic
      radius (RH) measurements from off-line quasi-elastic light scattering (QELS) and
      by RH distribution calculations and fractogram simulations obtained via a finite
      element analysis implementation of field-flow fractionation theory by
      commercially available software. As part of this study, we have investigated
      analyte recovery in HF5 and also possible reasons for discrepancies between
      calculated and simulated results vis-a-vis experimentally determined data.

PMID- 25578046
TI  - Filtration efficiency validation of glass wool during thermal desorption-gas
      chromatography-mass spectrometer analysis of fine atmospheric particles.
AB  - Thermal desorption-gas chromatography-mass spectrometer (TD-GC-MS) technique has
      been widely used for analysis of semi-violate organic compounds on atmospheric
      aerosol. To prevent GC column from being damaged by fine solid particles during
      thermal desorption process, glass wool as filter mat is indispensible. However,
      the filtration efficiency has never been validated. In this paper, the most
      penetrating particle size and the minimum packing thickness of glass wool were
      calculated based on classical filtration theory. According to the calculation
      results, packing parameters of glass wool were optimized experimentally using
      silica particles. It is demonstrated that glass wool with a packing thickness of
      30 mm, solidity of 0.039 can effectively block these fine solid particles from
      penetrating at normal thermal desorption conditions (T=300 degrees C, u=0.4-4
      cm/s). Finally, the filtration efficiency of glass wool was further confirmed
      with real PM2.5 samples. Under the validated filtration condition, TD-GC-MS was
      applied for the analysis of non-polar organic compounds on real PM2.5 samples,
      and very good results were obtained.

PMID- 25578054
TI  - Stem cell gene therapy for HIV: strategies to inhibit viral entry and
      replication.
AB  - Since the demonstration of a cure of an HIV+ patient with an allogeneic stem cell
      transplant using naturally HIV-resistant cells, significant interest in creating
      similar autologous products has fueled the development of a variety of "cell
      engineering" approaches to stem cell therapy for HIV. Among the more well-studied
      strategies is the inhibition of viral entry through disruption of expression of
      viral co-receptors or through competitive inhibitors of viral fusion with the
      cell membrane. Preclinical evaluation of these approaches often starts in vitro
      but ultimately is tested in animal models prior to clinical implementation. In
      this review, we trace the development of several key approaches (meganucleases,
      short hairpin RNA (shRNA), and fusion inhibitors) to modification of
      hematopoietic stem cells designed to impart resistance to HIV to their T-cell and
      monocytic progeny. The basic evolution of technologies through in vitro and in
      vivo testing is discussed as well as the pros and cons of each approach and how
      the addition of postentry inhibitors may enhance the overall antiviral efficacy
      of these approaches. 

PMID- 25578056
TI  - Changes in arterioportal shunts in hepatocellular carcinoma patients with portal
      vein thrombosis who were treated with chemoembolization followed by radiotherapy.
AB  - PURPOSE: In this study, we retrospectively investigated the prevalence of
      arterioportal (AP) shunts in hepatocellular carcinoma (HCC) patients with portal
      vein tumor thrombosis (PVTT) and evaluated the changes in AP shunts after
      chemoembolization followed by external beam radiation therapy (EBRT). MATERIALS
      AND METHODS: We analyzed 54 HCC patients with PVTT who were treated with
      chemoembolization followed by EBRT. EBRT was uniformly delivered at a total dose
      of 30 to 45 Gy (median, 35 Gy), with a daily dose of 2 to 4.5 Gy. Angiographic
      images of chemoembolization before and after radiation therapy (RT) were reviewed
      to investigate the AP shunt. RESULTS: During the initial session of
      chemoembolization, 33 of 54 patients (61%) had an AP shunt. After EBRT, 32 out of
      33 patients had an additional session of chemoembolization and were evaluated for
      a change in the AP shunt. The AP shunt decreased in 20 of 32 patients (63%) after
      chemoembolization followed by EBRT. The 1-year calculated overall survival (OS)
      rate for all patients was 52.6% and the 2-year OS was 36.4%. The median OS in all
      patients was 13 months. Patients with AP shunt showed poorer median OS than those
      without AP shunt, but there was no statistically significant difference (median,
      12 months vs. 17 months). CONCLUSION: The AP shunt frequently occurs in HCC
      patients with PVTT. This study suggests that a poor prognosis is associated with
      an AP shunt. Chemoembolization followed by RT may produce a decrease in AP
      shunts.

PMID- 25578055
TI  - T memory stem cells and HIV: a long-term relationship.
AB  - In analogy to many tissues in which mature, terminally differentiated cells are
      continuously replenished by the progeny of less differentiated, long-lasting stem
      cells, it has been suspected that memory T lymphocytes might contain small
      numbers of stem cell-like cells. However, only recently have such cells been
      physically identified and isolated from humans, mice, and nonhuman primates.
      These cells, termed "T memory stem cells" (TSCM), represent approximately 2-4 %
      of all circulating T lymphocytes, seem to be extremely durable, and can rapidly
      differentiate into more mature central memory, effector memory, and effector T
      cells, while maintaining their own pool size through homeostatic self-renewal.
      Although it is becoming increasingly evident that that these cells have critical
      roles for T cell homeostasis and maintaining life-long cellular immunity against
      microbial pathogens during physiological conditions, they also seem intrinsically
      involved in many key aspects of HIV/SIV disease pathogenesis. Current data
      suggest that CD4+ TSCM cells represent a core element of the HIV-1 reservoir in
      patients treated with suppressive antiretroviral therapy (ART) and that relative
      resistance of CD4+ TSCM cells to SIV represents a distinguishing feature of non
      pathogenic SIV infection in natural hosts. This article summarizes recent studies
      investigating the role of TSCM in HIV/SIV infection. 

PMID- 25578057
TI  - A Survey of Stereotactic Body Radiotherapy in Korea.
AB  - PURPOSE: The purpose of this study is to investigate the current status of
      stereotactic body radiotherapy (SBRT) in Korea. A nationwide survey was conducted
      by the Korean Stereotactic Radiosurgery Group of the Korean Society for Radiation
      Oncology (KROG 13-13). MATERIALS AND METHODS: SBRT was defined as radiotherapy
      with delivery of a high dose of radiation to an extracranial lesion in <= 4
      fractions. A 16-questionnaire survey was sent by e-mail to the chief of radiation
      oncology at 85 institutions in June 2013. RESULTS: All institutions (100%)
      responded to this survey. Of these, 38 institutions (45%) have used SBRT and 47
      institutions (55%) have not used SBRT. Regarding the treatment site, the lung
      (92%) and liver (76%) were the two most common sites. The most common schedules
      were 60 Gy/4 fractions for non-small cell lung cancer, 48 Gy/4 fractions for lung
      metastases, 60 Gy/3 fractions for hepatocellular carcinoma, and 45 Gy/3 fractions
      or 40 Gy/4 fractions for liver metastases. Four-dimensional computed tomography
      (CT) was the most common method for planning CT (74%). During planning CT, the
      most common method of immobilization was the use of an alpha cradle/vacuum-lock
      (42%). CONCLUSION: Based on this survey, conduct of further prospective studies
      will be needed in order to determine the appropriate prescribed doses and to
      standardize the practice of SBRT.

PMID- 25578058
TI  - Blockade of autophagy aggravates endoplasmic reticulum stress and improves
      Paclitaxel cytotoxicity in human cervical cancer cells.
AB  - PURPOSE: Autophagy is one of the ways to degrade unfolded proteins after
      endoplasmic reticulum (ER) stress. The purpose of this study is to determine
      whether a blockade of autophagy leads to aggravated endoplasmic reticulum stress,
      which then induces cells apoptosis in HeLa cells treated with paclitaxel.
      MATERIALS AND METHODS: Autophagy activation and the proapoptotic effects were
      characterized using monodansylcadaverine labeling and Hoechest staining,
      respectively. A Western blot analysis was used to detect the expression of
      apoptotic and autophagy-related genes. A flow cytometry was used to assess the
      cell apoptosis ratio. RESULTS: Paclitaxel exposure induced the aggregation of
      autophagosomes in the cytoplasms of cervical cancer HeLa cells. The expression of
      Beclin 1 and LC3 II were upregulated, but p62 was downregulated, which suggests
      that autophagy was promoted by paclitaxel. On the other hand, the expression of
      GRP78 obviously increased, suggesting that ER stress was induced after paclitaxel
      treatment. The cell proliferation assay indicated that a knockdown of Beclin 1
      sensitized HeLa cells to paclitaxel. Furthermore, paclitaxel-mediated apoptotic
      cell death was further potentiated by the pretreatment with autophagy inhibitor
      chloroquine or small interfering RNA against Beclin 1. These results suggest that
      an induction of autophagy by paclitaxel may induce cell survival rather than cell
      death in HeLa cells; moreover, inhibition of autophagy led to an aggravated ER
      stress and an induction of downstream apoptosis. CONCLUSION: Our results reveal
      autophagy induced by paclitaxel conferred protection of tumor cells against
      apoptosis, and blockade of autophagy subsequently aggravated ER stress, enhancing
      the apoptosis associated with paclitaxel treatment in HeLa cells.

PMID- 25578059
TI  - Inclusion Complexes of Hydroxy Propyl-beta-Cyclodextrin and Paliperidone:
      Preparation and Characterization.
AB  - In the present investigation, an attempt has been made to improve aqueous
      solubility of a BCS class II drug by making an inclusion complex with
      Hydroxypropyl-beta-cyclodextrin (HP-beta-CD). Paliperidone (PALI) was selected as
      a model drug for the study. It is practically insoluble in water with low oral
      bioavailability. It is a major active metabolite of risperidone approved for the
      treatment of schizophrenia in adults. The inclusion complexes were prepared in
      1:1 (PALI: HP-beta-CD) molar ratio. Phase solubility studies were performed
      according to Higuchi Connors method to determine the optimum conditions for the
      complexation. The prepared solid inclusion complexes were characterized by
      Differential Scanning Calorimetry (DSC), Fourier- Transform Infrared Spectroscopy
      (FT-IR), Powder X-ray Diffractometry (PXRD), Scanning Electron Microscopy (SEM)
      and Proton Nuclear Magnetic Resonance Spectroscopy ((1)H-NMR). Dissolution study
      was performed using USP apparatus II in phosphate buffer, pH 6.8 (37 +/- 0.5
      degrees C). The solid state characterization studies confirmed the formation of
      inclusion complex between PALI and HP-beta-CD. The aqueous solubility and in
      vitro dissolution study showed that the solubility and dissolution rate of drug
      were considerably improved by complexation with HP-beta-CD with respect to the
      drug alone. The enhanced solubility and dissolution may help to improve in-vivo
      performance of PALI. Thus, the binary complexation of PALI with HP-beta-CD can be
      used as an approach for its solubility enhancement.

PMID- 25578060
TI  - New Perspectives of HIV/AIDS Therapy Study.
AB  - HIV/AIDS (acquired immune deficient syndrome), a human infectious disease was
      once listed as the No. 1 disease killer in US (1993). After the invention of
      antiviral drug cocktails-high active anti-retroviral therapy (HAART), most HIV
      infected patients can survive much longer than with single antiviral drugs or
      vaccines alone. However, it turns out to be a chronic disease owing to being
      incapable to eradicate HIV from infectious patients. Furthermore, potential newly
      outbreak of HIV epidemics caused by widespread drug-resistance or viral mutations
      is still looming over the globe. In order to counteract these drawbacks and
      possibilities of HAART, many hurdles must be passed. More creative and
      revolutionary ideas and worldwide cooperation efforts among academics, drug
      developers and governmental funding bodies must be encouraged and promoted. In
      this perspective, many important drawbacks and weaknesses relating to HIV/AIDS
      therapies are outlined and possible future solutions are highlighted. 

PMID- 25578068
TI  - Reduction in the structural instability of cloned eukaryotic tandem-repeat DNA by
      low-temperature culturing of host bacteria.
AB  - Summary For accurate analyses of eukaryotic tandem-repeat DNA, it is often
      required to clone a genomic DNA fragment into a bacterial plasmid. It is,
      however, a serious problem that tandem-repeat DNA is frequently subjected to
      structural changes during maintenance or amplification in the host bacteria.
      Here, we show an example of a clear difference in the instability of tandem
      repeat DNA between different culturing temperatures. A fragment of monkey
      centromeric DNA carried by pUC19 was considerably degraded by culturing bacteria
      at 37  degrees C, but the damage was reduced at 25  degrees C. Thus, culturing
      temperature is a significant factor for avoiding degradation, in addition to the
      genotype of the host bacteria. 

PMID- 25578069
TI  - Editorial: change in editorship.

PMID- 25578070
TI  - Bitter fruits from the tree of knowledge: remarks on the current revulsion from
      science.

PMID- 25578071
TI  - How to swim with sharks: a primer.

PMID- 25578072
TI  - Strange symbiosis.

PMID- 25578074
TI  - Heterosis and the future of animal improvement.

PMID- 25578073
TI  - Reductionism: seven lessons.

PMID- 25578075
TI  - Can science be neutral?

PMID- 25578076
TI  - The asymptotic attitude.

PMID- 25578077
TI  - On Being Intelligent about Intelligence.

PMID- 25578078
TI  - Letters to the editor.

PMID- 25578079
TI  - The detection of toxigenic Corynebacterium ulcerans from cats with nasal
      inflammation in Japan.
AB  - Corynebacterium ulcerans (toxigenic C. ulcerans) produces the diphtheria toxin,
      which causes pharyngeal and cutaneous diphtheria-like disease in people, and this
      bacterium is commonly detected in dogs and cats that are reared at home. It is
      considered dangerous when a carrier animal becomes the source of infection in
      people. To investigate the carrier situation of toxigenic C. ulcerans of cats
      bred in Japan, bacteria were isolated from 37 cats with a primary complaint of
      rhinitis in 16 veterinary hospitals in Osaka. Toxigenic C. ulcerans was detected
      in two of the cats. By drug sensitivity testing, the detected bacterium was
      sensitive to all investigated drugs, except clindamycin. It appears necessary to
      create awareness regarding toxigenic C. ulcerans infection in pet owners because
      this bacterium is believed to be the causative organism for rhinitis in cats. 

PMID- 25578080
TI  - Indicators for chronic disease surveillance - United States, 2013.
AB  - Chronic diseases are an important public health problem, which can result in
      morbidity, mortality, disability, and decreased quality of life. Chronic diseases
      represented seven of the top 10 causes of death in the United States in 2010
      (Murphy SL, Xu J, Kochanek KD. Deaths: final data for 2010. Natl Vital Stat Rep
      2013;6. Available at http://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_04.pdf Adobe
      PDF file). Chronic diseases and risk factors vary by geographic area such as
      state and county, where essential public health interventions are implemented.
      The chronic disease indicators (CDIs) were established in the late 1990s through
      collaboration among CDC, the Council of State and Territorial Epidemiologists,
      and the Association of State and Territorial Chronic Disease Program Directors
      (now the National Association of Chronic Disease Directors) to enable public
      health professionals and policymakers to retrieve data for chronic diseases and
      risk factors that have a substantial impact on public health. This report
      describes the latest revisions to the CDIs, which were developed on the basis of
      a comprehensive review during 2011-2013. The number of indicators is increasing
      from 97 to 124, with major additions in systems and environmental indicators and
      additional emphasis on high-impact diseases and conditions as well as emerging
      topics. 

PMID- 25578082
TI  - Reflection and the Origin of Man's Mind.

PMID- 25578081
TI  - Comment on: small bowel mucosal damage in familial Mediterranean fever: results
      of capsule endoscopy screening.

PMID- 25578083
TI  - Soil-plant interface in the root-hair zone as a unity of opposites.

PMID- 25578084
TI  - To the new medical graduate.

PMID- 25578085
TI  - Promethean evolution as the biological basis of human freedom and equality.

PMID- 25578086
TI  - Mindless meaning; meaningless mind.

PMID- 25578088
TI  - Diane Weysham Ward v. Director of the Bureau of Vital Statistics, Louisiana State
      Health Department.

PMID- 25578087
TI  - On the nature of consciousness and of physical reality.

PMID- 25578090
TI  - The pharmacist and the management of arterial hypertension: the role of blood
      pressure monitoring and telemonitoring.
AB  - Randomized controlled trials have documented that a team of health care
      professionals which includes a physician, a nurse and a community pharmacist may
      improve the benefit and adherence of anti-hypertensive therapy. If such a health
      care model relies on blood pressure telemonitoring, it can promote a stronger
      relationship between health care professionals and patients, and further improve
      BP control of hypertension. The major benefit of this collaborative approach is
      to center the patient's management in a tailored way, providing comprehensive and
      preventive care based on health information technologies. In this review, the
      authors summarize recent clinical studies that evaluate the role of the community
      pharmacist in BP measurements, and in hypertension screening and control. The
      authors also describe the advantages of using blood pressure telemonitoring in
      home and ambulatory settings to evaluate potential alternatives to primary care
      in hypertension management. 

PMID- 25578091
TI  - Biomineralization of stable and monodisperse vaterite microspheres using silk
      nanoparticles.
AB  - The influence of silk fibroin (SF) on calcium carbonate (CaCO3) biomineralization
      has been investigated; however, the formation of small, uniform SF-regulated
      vaterite microspheres has not been reported. In this work, spherical CaCO3 was
      synthesized via coprecipitation in the presence of SF. SF nanostructures were
      first tuned by self-assembly at 60  degrees C to provide better control of the
      nucleation of CaCO3. Subsequently, monodisperse vaterite microspheres about 1.1
      MUm were generated by controlling aggregation and growth of CaCO3 under
      appropriate concentrations of SF and Ca ions. In contrast to unstable vaterite,
      the microspheres generated in the present study have sufficient stability in
      aqueous solution for at least 8 days without transformation into calcite, due to
      the electrostatic interactions between the Ca ions and the preassembled SF
      nanostructures. The microspheres as drug carriers of doxorubicin (DOX) were
      assessed and found to have good encapsulation efficiency, sustained drug release
      without burst release, and pH sensitivity. These new SF/CaCO3 hybrids may provide
      new options for various biomedical applications. 

PMID- 25578092
TI  - Interactomics: toward protein function and regulation.
AB  - Protein-protein interactions are central to all cellular processes. Understanding
      of protein-protein interactions is therefore fundamental for many areas of
      biochemical and biomedical research and will facilitate an understanding of the
      cell process-regulating machinery, disease causative mechanisms, biomarkers, drug
      target discovery and drug development. In this review, we summarize methods for
      populating and analyzing the interactome, highlighting their advantages and
      disadvantages. Applications of interactomics in both the biochemical and clinical
      arenas are presented, illustrating important recent advances in the field. 

PMID- 25578100
TI  - Risk factors for anaphylaxis in patients with mastocytosis.
AB  - INTRODUCTION: Symptoms resulting from the activation and release of mediators
      from the mast cells are observed in about 30% of the patients with mastocytosis.
      OBJECTIVES: The aim of the study was to assess the prevalence of anaphylactic
      reactions and to identify the risk factors for anaphylaxis in patients with
      mastocytosis depending on the type of the disease. Furthermore, we analyzed a
      response to treatment of mediator-related symptoms in this patient group.
      PATIENTS AND METHODS: The study group included 152 adult patients with
      mastocytosis. The diagnostic workup included a histopathological examination,
      flow cytometry, KIT mutation analysis, and measurement of tryptase levels. The
      diagnosis of allergy was confirmed by the skin prick test and serum
      immunoglobulin E levels. RESULTS: The prevalence of anaphylactic reactions in the
      study group was 50% and was higher in patients with systemic mastocytosis (P =
      0.007), specifically in its indolent variant (P = 0.026), than in patients with
      cutaneous mastocytosis. The most frequent triggers of anaphylaxis were food
      (29%), insect stings (22%), and drugs (15%). Tryptase levels were higher in
      patients with a history of anaphylaxis (P = 0.029) as well as in those with
      symptoms provoked by physical factors (P = 0.002). Such symptoms were reported in
      112 patients (74%) and were more common in patients with systemic mastocytosis
      compared with those with cutaneous mastocytosis (P = 0.026). The treatment was
      ineffective in 8 patients (10.5%) and resulted only in partial remission in 14
      patients (18.4%). CONCLUSIONS: The study showed a significant incidence of
      symptoms related to physical factors in patients with mastocytosis and
      anaphylaxis in history. Risk factors for anaphylaxis included increased serum
      tryptase levels and indolent variant of systemic mastocytosis. Standard
      pharmacological treatment was ineffective in 10% of the patients, who may require
      biological treatment.  

PMID- 25578102
TI  - Erratum: the effects of bronchiectasis on asthma exacerbation.
AB  - [This corrects the article on p. 209 in vol. 77, PMID: 25473408.]. 

PMID- 25578103
TI  - Structural study of various substituted biphenyls and their radical anions based
      on time-resolved resonance Raman spectroscopy combined with pulse radiolysis.
AB  - The structures of various para-substituted biphenyls (Bp-X; X = -OH, -OCH3, -CH3,
      -H, -CONH2, -COOH, and -CN) and their radical anions (Bp-X(*-)) were investigated
      by time-resolved resonance Raman spectroscopy combined with pulse radiolysis. The
      inter-ring C1-C1' stretching modes (nu6) of Bp-X were observed at ~1285 cm(-1),
      whereas the nu6 modes of Bp-X(*-) with an electron-donating or -withdrawing
      substituent were significantly up-shifted. The difference (Deltaf) between the
      nu6 frequencies of Bp-X and Bp-X(*-) showed a significant dependence on the
      electron affinity of the substituent and exhibited a correlation with the Hammett
      substituent constants (sigmap). In contrast to Bp-H(*-) with a planar geometry,
      the theoretical and experimental results reveal that all Bp-X(*-) with an
      electron-donating or -withdrawing substituent have a slightly twisted structure.
      The twisted structure of Bp-X(*-) is due to the localization of the unpaired
      electron and negative charge density on one phenyl moiety in Bp-X(*-). 

PMID- 25578097
TI  - Stress-induced chromatin changes in plants: of memories, metabolites and crop
      improvement.
AB  - Exposure of plants to adverse environmental conditions leads to extensive
      transcriptional changes. Genome-wide approaches and gene function studies have
      revealed the importance of chromatin-level control in the regulation of stress
      responsive gene expression. Advances in understanding chromatin modifications
      implicated in plant stress response and identifying proteins involved in
      chromatin-mediated transcriptional responses to stress are briefly presented in
      this review. We then highlight how chromatin-mediated gene expression changes can
      be coupled to the metabolic status of the cell, since many of the chromatin
      modifying proteins involved in transcriptional regulation depend on cofactors and
      metabolites that are shared with enzymes in basic metabolism. Lastly, we discuss
      the stability and heritability of stress-induced chromatin changes and the
      potential of chromatin-based strategies for increasing stress tolerance of crops.

PMID- 25578104
TI  - Enantioselective synthesis of alpha-quaternary Mannich adducts by palladium
      catalyzed allylic alkylation: total synthesis of (+)-sibirinine.
AB  - A catalytic enantioselective method for the synthesis of alpha-quaternary Mannich
      type products is reported. The two-step sequence of (1) Mannich reaction followed
      by (2) decarboxylative enantioselective allylic alkylation serves as a novel
      strategy to in effect access asymmetric Mannich-type products of "thermodynamic"
      enolates of substrates possessing additional enolizable positions and acidic
      protons. Palladium-catalyzed decarboxylative allylic alkylation enables the
      enantioselective synthesis of five-, six-, and seven-membered ketone, lactam, and
      other heterocyclic systems. The mild reaction conditions are notable given the
      acidic free N-H groups and high functional group tolerance in each of the
      substrates. The utility of this method is highlighted in the first total
      synthesis of (+)-sibirinine. 

PMID- 25578105
TI  - Mitochondrially targeted vitamin E succinate modulates expression of
      mitochondrial DNA transcripts and mitochondrial biogenesis.
AB  - AIMS: To assess the effect of mitochondrially targeted vitamin E (VE) analogs on
      mitochondrial function and biogenesis. RESULTS: Mitochondrially targeted vitamin
      E succinate (MitoVES) is an efficient inducer of apoptosis in cancer cells. Here,
      we show that unlike its untargeted counterpart alpha-tocopheryl succinate,
      MitoVES suppresses proliferation of cancer cells at sub-apoptotic doses by way of
      affecting the mitochondrial DNA (mtDNA) transcripts. We found that MitoVES
      strongly suppresses the level of the displacement loop transcript followed by
      those of mtDNA genes coding for subunits of mitochondrial complexes. This process
      is coupled to the inhibition of mitochondrial respiration, dissipation of the
      mitochondrial membrane potential, and generation of reactive oxygen species. In
      addition, exposure of cancer cells to MitoVES led to decreased expression of TFAM
      and diminished mitochondrial biogenesis. The inhibition of mitochondrial
      transcription was replicated in vivo in a mouse model of HER2(high) breast
      cancer, where MitoVES lowered the level of mtDNA transcripts in cancer cells but
      not in normal tissue. INNOVATION: Our data show that mitochondrially targeted VE
      analogs represent a novel class of mitocans that not only induce apoptosis at
      higher concentrations but also block proliferation and suppress normal
      mitochondrial function and transcription at low, non-apoptogenic doses.
      CONCLUSIONS: Our data indicate a novel, selective anti-cancer activity of
      compounds that act by targeting mitochondria of cancer cells, inducing
      significant alterations in mitochondrial function associated with transcription
      of mtDNA-coded genes. These changes subsequently result in the arrest of cell
      proliferation.

PMID- 25578116
TI  - Use of evidence-based guidelines reduces radioactive iodine treatment in patients
      with low-risk differentiated thyroid cancer.
AB  - OBJECTIVE: The goal was to determine if there was a relation between the
      introduction of evidence-based radioactive iodine (RAI) treatment guidelines for
      differentiated thyroid cancer (DTC) at Cedars-Sinai Medical Center (CSMC) and
      subsequent RAI use. In addition, we compared RAI treatment rates for DTC at CSMC
      to data from the National Cancer Database (NCDB) to see if the trends in RAI use
      at CSMC differed from the national trends. METHODS: RAI data from the CSMC
      Thyroid Cancer Center were reviewed to determine if RAI treatment was given
      appropriately. Kaplan-Meier curves were used to estimate disease-free survival
      for patients who received or did not receive treatment. RAI data from the NCDB
      were also used to compare how CSMC treatment rates compare nationally. RESULTS:
      There were 444 CSMC patients identified with DTC between 2009 and 2012.
      Approximately 95% of the patients had papillary thyroid cancer (n=423) with 65%
      in the stage I risk group (n=290). Kaplan-Meier curves for stages I-III show that
      those who did not receive RAI treatment had 100% disease-free survival, which was
      better than those who had received RAI. However, given that the total population
      in both stages II and III is quite small, having received RAI ablation was not
      found to be statistically significant. Stage I patients who received RAI had a
      significantly increased incidence of recurrent disease. The NCDB RAI rates for
      all DTC stages in each year have consistently been over 50% with an overall
      treatment rate of 57%. There were significant differences in the treatment rates
      between CSMC and NCDB, with a decrease in the use of RAI in low-risk patients
      with stage I tumors at CSMC following institution of the guidelines. CONCLUSION:
      Prudent use of RAI treatment should be considered for low-risk patients. Ablation
      rates have been decreasing steadily at CSMC, particularly among low-risk
      patients, with the adoption of more stringent RAI treatment guidelines. It is
      apparent from our data that physician practices can change with the
      implementation and dissemination of evidence-based guidelines for the treatment
      of DTC with RAI.

PMID- 25578121
TI  - Carcinogenesis and diabetic wound healing: evidences of parallelism.
AB  - There is a close association of chronic tissue damage, inflammation and cancer. A
      chronic injury may contribute to sustained healing response leading to fibrosis,
      organ failure and carcinogenesis. Wounds created due to mechanical or patho
      physiological insults, generally follow a sophisticated series of mutually
      coherent steps leading to the re-establishment of the affected tissue or organ.
      The process of wound healing resembles fundamental processes like embryogenesis
      and tissue regeneration. All the stages in the wound healing process are tightly
      regulated and any sort of imbalance may lead to either non healing chronic ulcers
      or excessively healed hypertrophic scars. Diabetic wounds are also very tough to
      heal and in many cases they do not heal, ultimately resulting in the amputation
      of that body part. The non-healing property of diabetic wounds may be due to
      combined effect of intrinsic and extrinsic factors. In this review, we aimed to
      explore the steps involved in diabetic wound healing and compare it with the
      process of carcinogenesis. This review demonstrates that both carcinogenesis and
      the diabetic wound healing follow a similar path of latent healing in an abnormal
      exaggerated manner. 

PMID- 25578122
TI  - Diagnostic workup of liver lesions: too long time with too many examinations.
AB  - OBJECTIVE: Liver mass lesions are often detected incidentally. Subsequent imaging
      examinations and surveillance are not only expensive, but may also cause
      unnecessary concern to patients. The aim of this study was to evaluate
      retrospectively the possible delay in acquiring the diagnosis of liver mass
      lesions, and to estimate the number of imaging examinations performed during the
      diagnostic workup. PATIENTS AND METHODS: The study comprised 200 patients with
      liver mass lesion of unknown etiology. The time needed from referral to final
      diagnosis was assessed. All imaging examinations and biopsy findings (if
      available) during the diagnostic workup were recorded. RESULTS: Out of the 200
      lesions, 133 were malignant, 65 with hepatocellular cancer and 26 with
      cholangiocarcinoma. All except one were diagnosed within 8 weeks. Of the 67
      benign lesions, there were 20 focal nodular hyperplasias and 20 hemangiomas. For
      the benign lesions, in 37% the diagnostic workup took >8 weeks. Repeated
      examinations were more common in benign lesions; but often redundant in both
      benign and malignant conditions in retrospect analysis. CONCLUSIONS: To confirm
      the diagnosis, benign lesions required more follow-up time and more repeated
      imaging examinations than malignant ones. A long surveillance for liver mass
      lesions in fear of malignancy seems not to be necessary, since virtually all
      malignant lesions were diagnosed within 8 weeks. Evaluating all lesions in a
      multidisciplinary team right from the beginning is advocated by a prospective
      study design.

PMID- 25578127
TI  - Otologic manifestations of acoustic neuroma.
AB  - CONCLUSION: Many patients with acoustic neuroma (AN) experience hearing loss and
      tinnitus. Time from first symptoms to diagnosis can be considerable. AN should be
      suspected, and MRI scans performed, in patients with hearing loss accompanied by
      asymmetry, tinnitus, low speech discrimination score (SDS), and abnormal auditory
      brainstem response (ABR). OBJECTIVES: To determine the otorhinolaryngological
      factors associated with AN by analyzing the clinical manifestations and
      diagnostic test results of patients with AN before MRI scanning. METHODS: This
      study enrolled 114 patients definitively diagnosed with AN after visiting the Ear
      Nose-and-Throat and Neurosurgery Departments of Kyung Hee University Medical
      Center from 2001 to 2013. Factors retrospectively analyzed included patient age,
      gender, major symptoms, accompanying symptoms, symptom duration, pure-tone
      audiometry, SDS, asymmetry, tinnitogram, ABR, and MRI scan results. RESULTS: The
      main symptom of AN was hearing loss, and the most frequent accompanying symptom
      was tinnitus. More severe deafness correlated significantly with lower SDS (p <
      0.05). Asymmetric hearing was observed in 75 of 116 patients (64.6%), and mean
      SDS was 73.1 +/- 34.1%. Of patients with latencies of waves I, III, and V on ABR
      tests, 56.1%, 92.4%, and 92.4%, had interaural latency differences >=0.2 ms.
      However, audiometry results did not correlate with lesion site or tumor size (p >
      0.05).

PMID- 25578128
TI  - Measurable impact of acupuncture on mucosal swelling of inferior turbinates: a
      prospective, randomized, controlled study.
AB  - CONCLUSIONS: Sham acupuncture turned out to be more effective than expected. The
      effect of acupuncture cannot be assessed by optical rhinometry (ORM). OBJECTIVES:
      In most cases nasal congestion is caused by hypertrophy of the inferior turbinate
      as a result of allergic and chronic rhinitis. Topical decongestants cause severe
      side effects. As a consequence, there is an increasing demand for alternative
      treatment options such as traditional Chinese medicine (TCM). METHODS: A total of
      25 patients with nasal congestion due to hypertrophic inferior turbinate were
      recruited. The mucosal swelling status of the inferior turbinate was assessed by
      continuous ORM for 20 min. Patients were asked to score the severity of their
      nasal congestion on a visual analogue scale (VAS) before and 10 and 20 min after
      acupuncture. Specific verum acupuncture points related to nasal congestion were
      tested against non-specific control sham acupuncture points. RESULTS: Sham
      acupuncture improved VAS scores, whereas ORM measured an increase in nasal
      swelling. The ORM revealed a quicker onset of the effect of verum acupuncture on
      the nasal blood flow. Also, verum acupuncture reaches its maximum effect in a
      shorter time period, so that the net reaction time was much shorter. However, ORM
      could not prove a decongestant effect of verum acupuncture on inferior turbinate.

PMID- 25578129
TI  - Contemporary therapeutic management of locally advanced hypopharyngeal cancer:
      oncologic and functional outcomes - a report on 100 cases.
AB  - CONCLUSION: A significant proportion of patients with locally advanced
      hypopharyngeal cancer could not be managed by larynx-sparing therapy. T4 stage is
      one of the main predictive factors of oncologic and functional outcomes.
      OBJECTIVES: To analyze the therapeutic management of patients with locally
      advanced hypopharyngeal cancer in clinical practice and to report oncologic and
      functional outcomes. METHODS: This was a retrospective study of all patients
      treated for a locally advanced hypopharyngeal squamous cell carcinoma between
      2001 and 2012 at our institution. RESULTS: A total of 100 patients were included
      in this study. Induction chemotherapy (CT) followed by radiotherapy (RT) +/- CT,
      primary RT + CT, and primary total pharyngolaryngectomy (TPL) comprised the
      initial therapeutic management for 54, 24, and 20 patients, respectively. Two
      patients received only supportive care. Overall survival (OS) and cause-specific
      survival (SS) were 50% and 60% at 3 years, respectively. In the group of patients
      referred for induction CT, the 3-year OS and SS were 58% and 70%, respectively.
      In multivariate analysis, T stage (p = 0.05) and ASA score (p = 0.02) were
      significant predictive factors of OS. T4 tumor stage had a pejorative impact on
      swallowing function after therapy (p = 0.006). The rate of patients alive,
      disease-free, and with a functional larynx at 2 years was 23%.

PMID- 25578135
TI  - [Patient care in the event of mass casualty incidents and disasters: General
      aspects].

PMID- 25578144
TI  - Investigation of genetic variants in ubiquitin enzyme genes involved in the
      modulation of neurodevelopmental processes: a role in schizophrenia
      susceptibility?
AB  - Despite extensive research during the last few decades, the etiology of
      schizophrenia remains unclear. Evidence of both genetic and environmental
      influences in the developmental profile of schizophrenia has grown, and due to
      the complexity of this disorder, a polygenic aspect has been associated with this
      neuropsychiatric pathology. Unfortunately, no diagnostic strategies based on
      biological measurement or genetic testing is currently available for
      schizophrenia. Gene-expression profiling and recent protein studies have shown a
      decrease in the expression of ubiquitin pathway proteins in the prefrontal cortex
      of schizophrenia patients. We have examined single nucleotide polymorphisms (or
      SNPs) within three genes from the ubiquitin protein system: the ubiquitin
      conjugating enzyme E2D1 (UBE2D1) gene, the E3 SUMO-protein ligase protein
      inhibitor of activated STAT 2 (PIAS2) gene, and the E3 ubiquitin ligase F-box and
      leucine-rich repeat protein 21 (FBXL21) gene, in a Caucasian case-control
      population for schizophrenia. After Bonferroni correction for multiple testing
      was applied, no significant associations were reported for any of the tested
      SNPs. Additional genetic analyses will be necessary to fully explore the role of
      these three genes in schizophrenia. Regarding the rising interest in ubiquitin
      related proteins as a therapeutic target in other pathologies such as cancer,
      further research into the role of ubiquitin pathways in schizophrenia seems
      topical and timely.

PMID- 25578145
TI  - Is there an interaction between socioeconomic status and FRAX 10-year fracture
      probability determined with and without bone density measures? Data from the
      Geelong Osteoporosis Study of female cohort.
AB  - FRAX((c)) evaluates 10-year fracture probabilities and can be calculated with and
      without bone mineral density (BMD). Low socioeconomic status (SES) may affect
      BMD, and is associated with increased fracture risk. Clinical risk factors differ
      by SES; however, it is unknown whether aninteraction exists between SES and FRAX
      determined with and without the BMD. From the Geelong Osteoporosis Study, we drew
      819 females aged >=50 years. Clinical data were collected during 1993-1997. SES
      was determined by cross-referencing residential addresses with Australian Bureau
      of Statistics census data and categorized in quintiles. BMD was measured by dual
      energy X-ray absorptiometry at the same time as other clinical data were
      collected. Ten-year fracture probabilities were calculated using FRAX
      (Australia). Using multivariable regression analyses, we examined whether
      interactions existed between SES and 10-year probability for hip and any major
      osteoporotic fracture (MOF) defined by use of FRAX with and without BMD. We
      observed a trend for a SES * FRAX(no-BMD) interaction term for 10-year hip
      fracture probability (p = 0.09); however, not for MOF (p = 0.42). In women
      without prior fracture (n = 518), we observed a significant SES * FRAX(no-BMD)
      interaction term for hip fracture (p = 0.03) and MOF (p = 0.04). SES does not
      appear to have an interaction with 10-year fracture probabilities determined by
      FRAX with and without BMD in women with previous fracture; however, it does
      appear to exist for those without previous fracture.

PMID- 25578146
TI  - The risk-stratified osteoporosis strategy evaluation study (ROSE): a randomized
      prospective population-based study. Design and baseline characteristics.
AB  - The risk-stratified osteoporosis strategy evaluation study (ROSE) is a randomized
      prospective population-based study investigating the effectiveness of a two-step
      screening program for osteoporosis in women. This paper reports the study design
      and baseline characteristics of the study population. 35,000 women aged 65-80
      years were selected at random from the population in the Region of Southern
      Denmark and-before inclusion-randomized to either a screening group or a control
      group. As first step, a self-administered questionnaire regarding risk factors
      for osteoporosis based on FRAX((r)) was issued to both groups. As second step,
      subjects in the screening group with a 10-year probability of major osteoporotic
      fractures >=15% were offered a DXA scan. Patients diagnosed with osteoporosis
      from the DXA scan were advised to see their GP and discuss pharmaceutical
      treatment according to Danish National guidelines. The primary outcome is
      incident clinical fractures as evaluated through annual follow-up using the
      Danish National Patient Registry. The secondary outcomes are cost-effectiveness,
      participation rate, and patient preferences. 20,904 (60%) women participated and
      included in the baseline analyses (10,411 in screening and 10,949 in control
      group). The mean age was 71 years. As expected by randomization, the screening
      and control groups had similar baseline characteristics. Screening for
      osteoporosis is at present not evidence based according to the WHO screening
      criteria. The ROSE study is expected to provide knowledge of the effectiveness of
      a screening strategy that may be implemented in health care systems to prevent
      fractures.

PMID- 25578147
TI  - Targeting disease by immunomodulation.

PMID- 25578148
TI  - Stefan Grimm, 1963-2014, a tragic loss for the scientific community.

PMID- 25578149
TI  - Hexokinase II integrates energy metabolism and cellular protection: Akting on
      mitochondria and TORCing to autophagy.

PMID- 25578150
TI  - Screening for Cushing's syndrome: is it worthwhile?
AB  - INTRODUCTION: Cushing's syndrome (CS) is a rare disease characterized by a
      collection of signs and symptoms, also common in the general population without
      elevated cortisol secretion. During the last years more patients with CS are
      identified earlier and with milder disease. Many of these patients are diagnosed
      during screening efforts performed for certain or isolated complaints like weight
      gain, diabetes mellitus (DM), hypertension, osteoporosis, elevated white blood
      cell counts and more. METHODS: In this review article the most popular screening
      test performed in the studies cited was the 1-mg dexamethasone suppression test.
      CONCLUSIONS: Cushing is not frequent enough to support the use of routine
      screening in patients with morbid obesity and type 2 DM. Also only 1% of
      hypertensive patients have secondary hypertension due to CS. However, screening
      should be considered in young patients with resistant DM and/or hypertension.
      Among patients with osteoporosis and vertebral fractures up to 5% were diagnosed
      with subclinical hypercortisolism; most of these had adrenal adenoma. Screening
      for CS is important in subjects with adrenal incidentaloma, and many studies show
      a high prevalence (~10%) of Cushing or subclinical CS in these patients.

PMID- 25578151
TI  - A short clinical history of multiple system atrophy.
AB  - In this article I shall review the history of multiple system atrophy (MSA)
      divided into three eras-1900 to 1969, 1969 to 1985, and 1985 to the present. 

PMID- 25578155
TI  - Potential coverage of circulating HPV types by current and developing vaccines in
      a group of women in Bosnia and Herzegovina with abnormal Pap smears.
AB  - The objectives of this study were to identify human papillomavirus (HPV)
      genotypes in a group of Bosnian-Herzegovinian women with abnormal cytology and to
      assess their potential coverage by vaccines. HPVs were identified by multiplex
      real-time PCR test (HPV High Risk Typing Real-TM; Sacace Biotechnologies, Italy)
      of 105 women with an abnormal cervical Pap smear and positive high-risk (HR) HPV
      DNA screening test. The most common genotypes in the study were HPV-16 (32.6%,
      48/147), HPV-31 (14.3%, 21/147), HPV-51 (9.5%, 14/147) and HPV-18 (7.5%, 11/147).
      The overall frequency of HR HPV-16 and/or HPV-18, covered by currently available
      vaccines [Gardasil(r) (Merck & Co., USA) and Cervarix(r); (GlaxoSmithKline, UK)]
      was lower than the overall frequency of other HPVs detected in the study (40.1%,
      59/174, P = 0.017). Group prevalence of HR HPVs targeted by a nine-valent vaccine
      in development (code-named V503) was higher than total frequency of other HPVs
      detected (68.0%, 100/147, P < 0.001). Development of cervical cytological
      abnormalities was independent of the presence of multiple infections (chi 2 =
      0.598, P = 0.741). Compared to other HPVs, dependence of cervical diagnosis and
      HPV-16, -18 (P = 0.008) and HPV-16, -18, -31 (P = 0.008) infections were
      observed. Vaccines targeting HR HPV-16, -18 and -31 might be an important tool in
      the prevention of cervical disease in Bosnia and Herzegovina. 

PMID- 25578156
TI  - Impact of acidity and metal ion on the antibacterial activity and mechanisms of
      beta- and alpha-chitosan.
AB  - This study investigated the effects of acidity and metal ion on the antibacterial
      activity of alpha- and beta-chitosan at different molecular weights (Mw, 22-360
      kDa) against Escherichia coli and Listeria innocua through agar well diffusion
      assay. Spectrophotometric, electrophoretic, and confocal fluorescence microscopy
      analysis were further employed to evaluate the antibacterial mechanisms probably
      involved. Increasing pH from 4.0 to 5.0 weakened the antibacterial ability of
      chitosan as shown by the decreased bacteria growth inhibition zone (BGIZ) from
      0.63 to 0.57 cm for beta-chitosan (61 kDa) and from 0.62 to 0.57 cm for alpha
      chitosan (30 kDa) against E. coli. All beta- and alpha-chitosan samples showed
      antibacterial activity against L. innocua, in which 22 kDa beta-chitosan and 30
      kDa alpha-chitosan at pH 4.0 had the highest antibacterial activity with BGIZ of
      1.22 and 0.98 cm, respectively. Interactive effect between pH and Mw on the
      antibacterial activity of beta-chitosan was observed, but not of alpha-chitosan.
      Adding Co(2+) and Ni(2+) significantly improved the antibacterial activity of
      chitosan, while adding K(+), Na(+), and Li(+) significantly weakened the
      antibacterial activity of some beta- and alpha-chitosan samples (P < 0.05), and
      different Mw and forms of chitosan showed different metal ion absorption
      capacities. Results indicate that chitosan might insert into the groove of
      bacterial DNA double helix structure to induce DNA degradation and permeate
      through bacteria cell membranes and combine with genomic DNA to induce its
      dysfunction, providing evidences for the antibacterial mechanisms of chitosan. 

PMID- 25578157
TI  - Physiological and molecular changes in barley and wheat under salinity.
AB  - In this study, it was aimed to compare salinity-induced changes in barley
      (Hordeum vulgare L. cv. Bornova-92) and bread wheat (Triticum aestivum L. cv.
      Gerek-79). Seeds were germinated under saline conditions (0, 50, 100, 250, and
      500 mM NaCl) for 2 days and recovered under non-saline conditions for 2 days. At
      the end of the salt treatment, germination, water content (WC), total soluble
      protein content, and catalase (CAT, EC 1.11.1.6) activity were affected in both
      species, while superoxide dismutase (SOD, EC 1.15.1.1) activity was affected in
      barley. Salinity affected WC, protein content, and CAT activity in both species,
      while it affected germination in barley and affected fresh weight and SOD
      activity in wheat after recovery. Physiological responses of both species were
      correlated. Expression of alpha-tubulin, Atls1, and Lls1 genes was down-regulated
      in barley after 250 mM NaCl treatment. HVA1 gene was highly (more than 50-fold)
      stimulated by salinity in barley. However, alpha-tubulin and Atls1 genes were
      down-regulated, and Lls1 gene was up-regulated in wheat after recovery from 250
      mM NaCl treatment. Increase in HVA1 expression was not significant in wheat. The
      expression profiles of barley and wheat under salinity are different, and barley
      tended to regulate gene expression faster than wheat. 

PMID- 25578158
TI  - Kinetic study of Candida antarctica lipase B immobilization using poly(methyl
      methacrylate) nanoparticles obtained by miniemulsion polymerization as support.
AB  - With the objective to obtain immobilized Candida antarctica lipase B (CalB) with
      good activity and improved utilization rate, this study evaluated the influence
      of enzyme and crodamol concentrations and initiator type on the CalB enzyme
      immobilization in nanoparticles consisting of poly(methyl methacrylate) (PMMA)
      obtained by miniemulsion polymerization. The kinetic study of immobilized CalB
      enzyme in PMMA nanoparticles was evaluated in terms of monomer conversion,
      particle size, zeta potential, and relative activity. The optimum immobilization
      condition for CalB was compared with free enzyme in the p-NPL hydrolysis activity
      measurement. Results showed a higher CalB enzyme stability after 20 hydrolysis
      cycles compared with free CalB enzyme; in particular, the relative immobilized
      enzyme activity was maintained up to 40%. In conclusion, PMMA nanoparticles
      proved to be a good support for the CalB enzyme immobilization and may be used as
      a feasible alternative catalyst in industrial processes.

PMID- 25578159
TI  - Predicting therapeutic response in patients with heart failure: the story of C
      reactive protein.
AB  - Heart failure continues to be a major public health burden in the USA. With
      markedly high rates of morbidity and mortality upon diagnosis, effective
      treatment and prognosis are critical in the management of chronic heart failure.
      Growing evidence now supports the hypothesis that inflammation plays a key role
      in the progression and worsening of heart failure. Of the various inflammatory
      mediators identified, C-reactive protein, an acute phase inflammatory marker, has
      been associated with poor prognosis in patients with heart failure. Several
      interventional studies have been investigated to explore C-reactive protein
      modulation and potential treatment options and health outcomes; however, further
      studies are warranted before C-reactive protein-targeted therapy may be
      recommended in the management of heart failure. 

PMID- 25578160
TI  - The fly in the social ointment.

PMID- 25578161
TI  - Biology without Consciousness-and Its Consequences.

PMID- 25578162
TI  - The lengthened line.

PMID- 25578163
TI  - The Ethical Relationship between Humans and Other Organisms.

PMID- 25578164
TI  - Computers and medical discoveries.

PMID- 25578165
TI  - The Rise and Decline of a Professor-a Fable.

PMID- 25578166
TI  - Ethical responsibilities in clinical investigation.

PMID- 25578167
TI  - Medicare in utopia.

PMID- 25578168
TI  - The hours of changing responsiveness or susceptibility.

PMID- 25578169
TI  - Some genetic aspects of therapeutic abortion.

PMID- 25578170
TI  - Diabetes mellitus-1967.

PMID- 25578171
TI  - The use of empathy in the resolution of grief.

PMID- 25578172
TI  - The Viral Masquerader's Vendetta.

PMID- 25578173
TI  - An approach to tumor virus identification.

PMID- 25578174
TI  - Letters to the editor.

PMID- 25578175
TI  - Platycodin D Attenuates Airway Inflammation in a Mouse Model of Allergic Asthma
      by Regulation NF-kappaB Pathway.
AB  - In this work, the anti-asthma potential of platycodin D (PLD) was studied by
      investigation of its effect to suppress airway inflammation, a murine model of
      asthma and the possible mechanisms. A total of 50 mice were randomly assigned to
      five experimental groups: control, ovalbumin (OVA), OVA+dexamethasone (2 mg/kg)
      and OVA+PLD (40, 80 mg/kg). Airway resistance (Raw) were measured; airway
      histological studies were evaluated by the hematoxylin and eosin (HE) staining;
      interleukin-4 (IL-4), interleukin-5(IL-5), and interleukin-13 in bronchoalveolar
      lavage fluid (BALF) were evaluated by enzyme-linked immunosorbent assay (ELISA);
      NF-kappaBp65, p-NF-kappaBp65, p-IKKalpha, IKKalpha, p-IKKbeta, p-IkBalpha, and
      IkBalpha of airway were measured by Western blotting. Our study demonstrated that
      PLD inhibited OVA-induced increases in Raw and eosinophil count in airway; IL-4,
      IL-5, and IL-13 were recovered in BALF. Histological studies demonstrated that
      PLD substantially inhibited OVA-induced eosinophilia in airway tissue. Western
      blotting studies demonstrated that PLD substantially inhibited NF-kappaB pathway.
      These findings suggest that PLD may effectively ameliorate the progression of
      asthma and could be used as a therapy for patients with allergic asthma.

PMID- 25578176
TI  - Transport of Human Adenoviruses in Water Saturated Laboratory Columns.
AB  - Groundwater may be contaminated with infective human enteric viruses from various
      wastewater discharges, sanitary landfills, septic tanks, agricultural practices,
      and artificial groundwater recharge. Coliphages have been widely used as
      surrogates of enteric viruses, because they share many fundamental properties and
      features. Although a large number of studies focusing on various factors (i.e.
      pore water solution chemistry, fluid velocity, moisture content, temperature, and
      grain size) that affect biocolloid (bacteria, viruses) transport have been
      published over the past two decades, little attention has been given toward human
      adenoviruses (hAdVs). The main objective of this study was to evaluate the effect
      of pore water velocity on hAdV transport in water saturated laboratory-scale
      columns packed with glass beads. The effects of pore water velocity on virus
      transport and retention in porous media was examined at three pore water
      velocities (0.39, 0.75, and 1.22 cm/min). The results indicated that all
      estimated average mass recovery values for hAdV were lower than those of
      coliphages, which were previously reported in the literature by others for
      experiments conducted under similar experimental conditions. However, no obvious
      relationship between hAdV mass recovery and water velocity could be established
      from the experimental results. The collision efficiencies were quantified using
      the classical colloid filtration theory. Average collision efficiency, alpha,
      values decreased with decreasing flow rate, Q, and pore water velocity, U, but no
      significant effect of U on alpha was observed. Furthermore, the surface
      properties of viruses and glass beads were used to construct classical DLVO
      potential energy profiles. The results revealed that the experimental conditions
      of this study were unfavorable to deposition and that no aggregation between
      virus particles is expected to occur. A thorough understanding of the key
      processes governing virus transport is pivotal for public health protection.

PMID- 25578177
TI  - Evaluation of two commercially available immunological kits for the diagnosis of
      Helicobacter spp. in bottlenose dolphins (Tursiops truncatus).
AB  - Helicobacter pylori is considered to be responsible for the most common gastric
      infections in humans worldwide. In animals, other Helicobacter species are linked
      to gastritis with and without the presence of ulcers in their respective hosts.
      Moreover, gastric ulcers have been reported for decades in wild and captive
      dolphins. Clinical signs include lack of appetite, anorexia, abdominal
      tenderness, depression, and occasional unresponsiveness. In this study, serum and
      stool of nine bottlenose dolphins from Loro Parque collection Tenerife, Spain
      were examined for the presence of Helicobacter spp. The aim of our study was to
      evaluate the use of two commercially available kits for the detection of H.
      pylori in humans: a stool antigen immunoassay (Letitest H. pylori CARD) and a
      Western blot assay (EUROLINE-WB H. pylori) that were adapted to identify specific
      Helicobacter spp. antibodies in the tested Loro Parque bottlenose dolphin
      collection. The utility of these diagnostic kits for their application in
      dolphins is demonstrated, and their use in the future for the diagnosis of
      Helicobacter spp. in both wild and captive dolphins is proposed in this study.

PMID- 25578178
TI  - Progressive multifocal leukoencephalopathy after interferon beta-1a monotherapy.

PMID- 25578179
TI  - Association of progranulin polymorphism rs5848 with neurodegenerative diseases: a
      meta-analysis.
AB  - The purpose of this meta-analysis was to investigate the association between
      progranulin polymorphism rs5848 and risk of the neurodegenerative diseases
      frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), Parkinson's
      disease (PD), and amyotrophic lateral sclerosis (ALS). Published literature from
      PubMed and other databases were retrieved, and 16 case-control studies were
      identified as eligible: 5 on FTLD (1,439 cases, 4,461 controls), 5 on AD (2,502
      cases, 2,162 controls), 3 on PD (1,605 cases, 1,591 controls), and 3 on ALS (663
      cases, 811 controls). The pooled odds ratio (OR) and 95% confidence interval (CI)
      were calculated. We found that rs5848 was associated with an increased risk of
      neurodegenerative diseases in the homozygous (TT vs. CC: OR, 1.24; 95% CI, 1.10
      1.39; P < 0.001) and recessive models (TT vs. CC + CT: OR, 1.23; 95% CI, 1.10
      1.37; P < 0.001). Stratified analyses showed associations of rs5848 with
      increased risk of AD and PD in the homozygous and recessive models. Our data
      indicate that rs5848 is associated with risk of AD and PD, suggesting important
      roles of progranulin in neurodegenerative processes.

PMID- 25578180
TI  - Far transfer effect associated with video game balance training in multiple
      sclerosis: from balance to cognition?

PMID- 25578187
TI  - Introduction to RNA-based vaccines and therapeutics.

PMID- 25578181
TI  - YKL-40 is correlated with FEV1 and the asthma control test (ACT) in asthmatic
      patients: influence of treatment.
AB  - BACKGROUND: YKL-40 is also called chitinase-3-like-1 (CHI3L1) protein and may be
      a marker for asthma. The aims of the present study were to investigate whether
      serum YKL-40 levels are stable or decreased in patients with asthma after
      appropriate treatment and to evaluate the correlation of YKL-40 levels with lung
      function and asthma control test (ACT) results. METHODS: A total of 103 asthmatic
      patients (mean age 33.1 +/- 0.9 years) with diagnosed asthma were enrolled in our
      study. All patients underwent a detailed clinical examination and completed the
      ACT questionnaire, serum YKL-40 measurement, and spirometry before (visit 1) and
      8 weeks after initiation of treatment (visit 2). RESULTS: At the follow-up, the
      median serum YKL-40 level was significantly decreased compared to the levels at
      visit 1 (75.2 [55.8-86.8] ng/ml versus 54.5 [46.4-58.4] ng/ml, p < 0.001). The
      serum YKL-40 level was negatively correlated with %FEV1 (r = -0.37, p < 0.001)
      and ACT score (r = -0.26, p = 0.007) at visit 1. The change in serum YKL-40
      levels between the visits was significantly correlated with changes in FEV1 (r = 
      0.28, p = 0.006) and ACT score (r = -0.22, p = 0.037). Patients with elevated YKL
      40 levels had significantly greater corticosteroid use than patients with lower
      levels. CONCLUSIONS: YKL-40 was reduced in the serum of asthmatic patients after
      appropriate treatment, and the levels correlated with improvements in %FEV1 and
      ACT. High levels of serum YKL-40 may be refractory to current asthma treatments.
      TRIAL REGISTRATION: ChiCTR-OCC-13003316.

PMID- 25578204
TI  - Analysis of anatomical risk factors for persistent type II endoleaks following
      endovascular abdominal aortic aneurysm repair using CT angiography.
AB  - PURPOSE: To predict persistent type II endoleaks (pT2Es) following endovascular
      aneurysm repair (EVAR) of abdominal aortic aneurysms, we examined factors related
      to post-EVAR pT2Es. METHODS: Eighty-four cases of EVAR were analyzed. T2Es that
      persisted for >=6 months were defined as pT2Es. pT2Es flowing from an inferior
      mesenteric artery (IMA) and lumbar artery (LA) were termed pIMA-T2Es and pLA
      T2Es, respectively. The anatomical factors concerning the aneurysm, IMA and LAs
      were assessed in the preoperative CT angiography images. A statistical analysis
      was performed on the factors associated with pT2Es. RESULTS: The incidence of
      pT2Es was 25 %. pT2Es were associated with postoperative changes in the aneurysm
      diameter. A univariate analysis showed that a sac thrombus and the number of
      patent side branches arising from an aneurysm were significant factors associated
      with pT2Es. The IMA diameters were significantly larger in cases of pIMA-T2Es.
      The significant factors associated with pLA-T2Es were a circumferential thrombus,
      the number of patent LAs and the mean LA diameter. Multivariate analyses
      indicated that a circumferential thrombus was a protective factor for pT2Es,
      whereas an IMA >=2.6 mm and each additional LA branch >=1.9 mm were powerful risk
      factors for a pT2E. CONCLUSION: Significant anatomical factors associated with
      pT2E were found in this study. These factors may be useful in selecting patients
      for perioperative intervention.

PMID- 25578209
TI  - Corrigendum: comparison of short-term postoperative outcomes in totally
      laparoscopic distal gastrectomy versus laparoscopy-assisted distal gastrectomy.
AB  - [This corrects the article on p. 105 in vol. 14, PMID: 25061537.]. 

PMID- 25578210
TI  - Emerging drugs for the treatment of cervical cancer.
AB  - INTRODUCTION: Worldwide, most cervical cancer (CC) patients require the use of
      drug therapy either adjuvant, concurrent with radiation or palliative. AREAS
      COVERED: This review briefly discusses the current achievements in treating CC
      with an emphasis in emerging agents. EXPERT OPINION: Concurrent cisplatin with
      radiation and lately, gemcitabine-cisplatin chemoradiation has resulted in small
      but significant improvements in the treatment of locally advanced and high-risk
      early-stage patients. So far, only antiangiogenic therapy with bevacizumab added
      to cisplatin chemoradiation has demonstrated safety and encouraging results in a
      Phase II study. In advanced disease, cisplatin doublets yield median survival
      rates not exceeding 14 months. The first Phase III study of bevacizumab, added to
      standard chemotherapy cisplatin- or non-cisplatin-containing doublet, has shown
      significant increase in both overall survival and progression-free survival.
      Further studies are needed before bevacizumab plus chemotherapy can be considered
      the standard of care for advanced disease. The characterization of the mutational
      landscape of CC and developments of novel targeted therapies may result in more
      effective and individualized treatments for CC. The potential efficacy of
      knocking down the key alterations in CC, E6 and E7 human papilloma virus
      oncoproteins must not be overlooked.

PMID- 25578216
TI  - Subclinical ketosis in post-partum dairy cows fed a predominantly pasture-based
      diet: defining cut-points for diagnosis using concentrations of beta
      hydroxybutyrate in blood and determining prevalence.
AB  - AIMS: Firstly, to define, in dairy cows in the first 5 weeks post-calving fed a
      predominantly pasture-based diet, cut-points of concentrations of beta
      hydroxybutyrate (BHBA) in blood, above which there were associations with
      purulent vaginal discharge (PVD), reduced pregnancy rates (PR) and decreased milk
      production, in order to better define subclinical ketosis (SCK) in such cattle;
      and secondly, to determine the prevalence, incidence and risk factors for SCK.
      METHODS: An observational field study was conducted in 565 cows from 15 spring
      calving and predominantly pasture-fed dairy herds in two regions of New Zealand
      during the 2010- 2011 dairy season. Within each herd, a cohort of randomly
      selected cows (approximately 40 per herd) was blood sampled to determine
      concentrations of BHBA on six occasions at weekly intervals starting within 5
      days of calving. The key outcome variables were the presence/absence of PVD at 5
      weeks post-calving, PR after 6 weeks (6-week PR) and after the completion of the
      breeding season (final PR), and mean daily milk solids production. RESULTS: Two
      cut-points for defining SCK were identified: firstly concentration of BHBA in
      blood>=1.2 mmol/L within 5 days post-calving, which was associated with an
      increased diagnosis of PVD (24 vs. 8%); and secondly concentration of BHBA in
      blood>=1.2 mmol/L at any stage within 5 weeks post-calving, which was associated
      with decreased 6-week PR (78 vs. 85%). The mean herd-level incidence of SCK
      within 5 weeks post-calving was 68 (min 12; max 100)% and large variations
      existed between herds in peak prevalence of SCK and the interval post-calving at
      which such peaks occurred. Cows>8 years of age and cows losing body condition
      were at increased risk of SCK within 5 weeks of calving. CONCLUSIONS: Cows with
      concentration of BHBA in blood>=1.2 mmol/L in early lactation had a higher risk
      of PVD and lower 6-week PR. Cow and herd-level prevalence of SCK varied widely in
      early lactation. CLINICAL RELEVANCE: Subclinical ketosis is common and is
      significantly associated with reproductive performance in mainly pasture-fed New
      Zealand dairy cattle. Controlling SCK may therefore result in improvements in
      herd reproductive performance. However considerable variation exists among herds
      in the incidence of SCK and in the timing of peak prevalence which means that
      herd-specific monitoring programmes are required to define herd SCK status
      accurately.

PMID- 25578217
TI  - Coronary artery disease: the magnificent fifty?

PMID- 25578218
TI  - Strength of recommendations in WHO guidelines using GRADE was associated with
      uptake in national policy.
AB  - OBJECTIVES: This study assesses the extent to which the strength of a
      recommendation in a World Health Organization (WHO) guideline affects uptake of
      the recommendation in national guidelines. STUDY DESIGN AND SETTING: The uptake
      of recommendations included in HIV and TB guidelines issued by WHO from 2009 to
      2013 was assessed across guidelines from 20 low- and middle-income countries in
      Africa and Southeast Asia. Associations between characteristics of
      recommendations (strength, quality of the evidence, type) and uptake were
      assessed using logistic regression. RESULTS: Eight WHO guidelines consisting of
      109 strong recommendations and 49 conditional recommendations were included, and
      uptake assessed across 44 national guidelines (1,255 recommendations) from 20
      countries. Uptake of WHO recommendations in national guidelines was 82% for
      strong recommendations and 61% for conditional recommendations. The odds of
      uptake comparing strong recommendations and conditional recommendations was 1.9
      (95% confidence interval: 1.4, 2.7), after adjustment for quality of evidence.
      Higher levels of evidence quality were associated with greater uptake,
      independent of recommendation strength. CONCLUSION: Guideline developers should
      be confident that conditional recommendations are frequently adopted. The fact
      that strong recommendations are more frequently adopted than conditional
      recommendations underscores the importance of ensuring that such recommendations
      are justified.

PMID- 25578228
TI  - Comparing the prognostic performance of ASSIST to interleukin-6 and procalcitonin
      in patients with severe sepsis or septic shock.
AB  - CONTEXT: We recently derived and validated a multi-biomarker-based model (ASSIST)
      to stratify patients with sepsis based on initial mortality risk. OBJECTIVE: The
      objective of this study was to compare the performance of ASSIST to interleukin-6
      (IL6) and procalcitonin (PCT). METHODS: The area-under-the-receiver operating
      characteristic curve for predicting 28-d mortality using ASSIST was compared with
      that of IL6 (n = 452) and PCT (n = 235). RESULTS: The area under the curve for
      ASSIST was greater than that of IL6 and PCT. CONCLUSIONS: ASSIST estimated the
      probability of mortality more reliably than IL6 and PCT in this cohort of
      patients with sepsis.

PMID- 25578229
TI  - Understanding the biokinetics of ibuprofen after single and repeated treatments
      in rat and human in vitro liver cell systems.
AB  - Common in vitro toxicity testing often neglects the fate and intracellular
      concentration of tested compounds, potentially limiting the predictability of in
      vitro results for in vivo extrapolation. We used in vitro long-term cultures of
      primary rat (PRH) and human hepatocytes (PHH) and HepaRG cells to characterise
      and model the biokinetic profile of ibuprofen (IBU) after single and daily
      repeated exposure (14 days) to two concentrations. A cross-model comparison was
      carried out at 100MUM, roughly corresponding to the human therapeutic plasma
      concentration. Our results showed that IBU uptake was rapid and a dynamic
      equilibrium was reached within 1 or 2 days. All three cell systems efficiently
      metabolised IBU. In terms of species-differences, our data mirrored known in vivo
      results. Although no bioaccumulation was observed, IBU intracellular
      concentration was higher in PRH due to a 10-fold lower metabolic clearance
      compared to the human-derived cells. In HepaRG cells, IBU metabolism increased
      over time, but was not related to the treatment. In PHH, a low CYP2C9 activity,
      the major IBU-metabolising CYP, led to an increased cytotoxicity. A high inter
      individual variability was seen in PHH, whereas HepaRG cells and PRH were more
      reproducible models. Although the concentrations of IBU in PRH over time differed
      from the concentrations found in human cells under similar exposure conditions. 

PMID- 25578230
TI  - The role of NF-kappaB signaling pathway in polyhexamethylene guanidine phosphate
      induced inflammatory response in mouse macrophage RAW264.7 cells.
AB  - Polyhexamethylene guanidine (PHMG) phosphate is a competitive disinfectant with
      strong antibacterial activity. However, epidemiologists revealed that inhaled
      PHMG-phosphate may increase the risk of pulmonary fibrosis associated with
      inflammation, resulting in the deaths of many people, including infants and
      pregnant women. In addition, in vitro and in vivo studies reported the
      inflammatory effects of PHMG-phosphate. Therefore, the aim of the present study
      was to clarify the inflammatory effects and its mechanism induced by PHMG
      phosphate in murine RAW264.7 macrophages. Cell viability, inflammatory cytokine
      secretion, nuclear factor kappa B (NF-kappaB) activation, and reactive oxygen
      species (ROS) generation were investigated in macrophages exposed to PHMG
      phosphate. PHMG-phosphate induced dose-dependent cytotoxicity, with LC50 values
      of 11.15-0.99mg/ml at 6 and 24h, respectively. PHMG-phosphate induced pro
      inflammatory cytokines including IL-1beta, IL-6, and IL-8. In particular, IL-8
      expression was completely inhibited by the NF-kappaB inhibitor BAY11-7082. In
      addition, PHMG-phosphate decreased IkappaB-alpha protein expression and increased
      NF-kappaB-mediated luciferase activity, which was diminished by N-acetyl-l
      cystein. However, abundant amounts of ROS were generated in the presence of PHMG
      phosphate at high concentrations with a cytotoxic effect. Our results
      demonstrated that PHMG-phosphate triggered the activation of NF-kappaB signaling
      pathway by modulating the degradation of IkappaB-alpha. Furthermore, the NF
      kappaB signaling pathway plays a critical role in the inflammatory responses
      induced by PHMG-phosphate. We assumed that ROS generated by PHMG-phosphate were
      associated with inflammatory responses as secondary mechanism. In conclusion, we
      suggest that PHMG-phosphate induces inflammatory responses via NF-kappaB
      signaling pathway. 

PMID- 25578231
TI  - Assessing the utilization of functional imaging in multiparametric prostate MRI
      in routine clinical practice.
AB  - AIM: To evaluate the utilization of functional imaging tests in multiparametric
      (mp)-MRI of the prostate in routine practice and to assess whether education
      improves usage. MATERIALS AND METHODS: With research ethics board approval, 254
      patients underwent mp-MRI [diffusion-weighted imaging (DWI) and dynamic contrast
      enhancement (DCE)] over a 1-year period at a single tertiary-care referral centre
      for prostate disease. All studies were reported by fellowship-trained abdominal
      radiologists. To determine to what extent parametric tests were used, radiology
      reports were searched for terms indicating usage of DWI/DCE and studies were
      reviewed to determine whether post-processing of DCE was performed. Midway
      through the study, an internal continuing medical education (CME) programme was
      instituted (consisting of lectures, electronic reading material, intra- and inter
      departmental prostate rounds) and a standardized reporting template was
      introduced. Utilization of functional imaging was compared between radiologists
      by years of experience and by number of examinations interpreted, by study
      indication, and before and after CME. RESULTS: Overall, both DWI and DCE were
      used in 50.7% of examinations. DWI (67.3%) was more frequently used than DCE
      (56.3%). DCE contrast curves were generated in 33.5% of studies, and quantitative
      analysis was performed in only one patient. Use of parametric tests was higher
      after CME (60.6% versus 40.4%), p = 0.009. There was no correlation between the
      use of parametric tests and years of experience, (p = 0.94), and there was no
      association with the number of examinations interpreted (p = 0.19-0.97). There
      was no association between the use of parametric tests and study indication, (p =
      0.16); however, contrast curves were produced more frequently in non-staging
      studies, (p = 0.027). CONCLUSION: Parametric tests were underutilized in routine
      practice. DWI was used more commonly than DCE. CME was associated with increased
      utilization of mp-MRI.

PMID- 25578232
TI  - Large-scale green chemical synthesis of adjacent quaternary chiral centers by
      continuous flow photodecarbonylation of aqueous suspensions of nanocrystalline
      ketones.
AB  - To demonstrate the ease of scale-up and synthetic potential of some organic solid
      state reactions, we report the synthesis, crystallization, and solid state
      photochemistry of acyclic, homochiral, hexasubstituted (+)-(2R,4S)-2-carbomethoxy
      4-cyano-2,4-diphenyl-3-pentanone 1. We demonstrate that solid state
      photodecarbonylation of (+)-(2R,4S)-1 affords (+)-(2R,3R)-2-carbomethoxy-3-cyano
      2,3-diphenyl-butane 2 with two adjacent stereogenic, all-carbon substituted
      quaternary centers, in quantitative chemical yield and 100% diastereoselectivity
      and enantiomeric excess. The efficient multigram photodecarbonylation of (+)
      (2R,4S)-1 as a nanocrystalline suspension in water using a continuous flow
      photoreactor shows that the large-scale synthesis of synthetically challenging
      compounds using photochemical synthesis in the solid state can be executed in a
      remarkably simple manner. 

PMID- 25578233
TI  - The university of chicago medical center celebrates fifty years.

PMID- 25578234
TI  - Anton j. Carlson: a biographical sketch.

PMID- 25578235
TI  - Franklin Chambers McLean and the Founding of the University of Chicago School of
      Medicine.

PMID- 25578236
TI  - The cultivation of excellence.

PMID- 25578237
TI  - Genetic approaches to control of influenza.

PMID- 25578238
TI  - The interdigestive housekeeper of the gastrointestinal tract.

PMID- 25578239
TI  - The cell biology of gametogenesis in the male.

PMID- 25578240
TI  - New endocrinology of the brain.

PMID- 25578241
TI  - Two decades of experimental and clinical orthotopic homotransplantation of the
      heart.

PMID- 25578242
TI  - Bone morphodifferentiation and tumorigenesis.

PMID- 25578243
TI  - Inhibition of prenyltransferase activity by statins in both liver and muscle cell
      lines is not causative of cytotoxicity.
AB  - As inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, statins are an
      important first-line treatment for hypercholesterolemia. However, a recognized
      side-effect of statin therapy is myopathy, which in severe cases can present as
      potentially fatal rhabdomyolysis. This represents an important impediment to
      successful statin therapy, and despite decades of research the molecular
      mechanisms underlying this side-effect remain unclear. Current evidence supports
      a role for reduced levels of mevalonate pathway intermediates, with the most
      accepted hypothesis being a reduction in isoprenoids formation, leading to faulty
      post-translational modifications of membrane-associated proteins. We have
      undertaken a comprehensive analysis of the impact of nine statins on two human
      cell lines; Huh7 hepatoma and RD rhabdomyosarcoma. In both cell lines,
      concentration-dependent inhibition of prenylation was observed for cerivastatin
      and simvastatin, which could be rescued with the pathway intermediate mevalonate;
      in general, muscle cells were more sensitive to this effect, as measured by the
      levels of unprenylated Rap1A, a marker for prenylation by geranylgeranyl
      transferase I. Concentration-dependent toxicity was observed in both cell lines,
      with muscle cells again being more sensitive. Importantly, there was no
      correlation between inhibition of prenylation and cell toxicity, suggesting they
      are not causally linked. The lack of a causal relationship was confirmed by the
      absence of cytotoxicity in all cell lines following exposure to specific
      inhibitors of geranylgeranyl transferases I and II, and farnesyl transferase. As
      such, we provide strong evidence against the commonly accepted hypothesis linking
      inhibition of prenylation and statin-mediated toxicity, with the two processes
      likely to be simultaneous but independent. 

PMID- 25578244
TI  - Be wary of awareness--lessons from NAP5 for obstetric anaesthetists.

PMID- 25578245
TI  - Codeine and breast-feeding mothers.

PMID- 25578247
TI  - Putting allergy/immunology into context: analysis of the 2012 US Medicare
      reimbursement data.

PMID- 25578248
TI  - Mixing compatibilities of Aspergillus and American cockroach allergens with other
      high-protease fungal and insect extracts.
AB  - BACKGROUND: Recent studies have shown that Alternaria and German cockroach
      allergens can be degraded by endogenous proteases from other insect and fungal
      extracts when combined for immunotherapy, but data supporting the compatibilities
      of other high-protease products in comparable mixtures have not been reported.
      OBJECTIVE: To assess the stabilities and compatibilities of Aspergillus fumigatus
      and American cockroach allergens after mixing with protease-rich extracts from
      other insects or fungi at concentrations similar to those recommended for
      subcutaneous immunotherapy. METHODS: Mixtures containing A fumigatus, American
      cockroach, and other fungal or insect extracts were evaluated by quantitative
      (enzyme-linked immunosorbent assays) and qualitative (immunoblotting) methods.
      Test mixtures and control samples at 10% to 50% glycerin concentrations were
      analyzed after storage for up to 12 months at 2 degrees C to 8 degrees C.
      RESULTS: Moderate to high recoveries of Aspergillus extract activities were
      retained in control samples and extract mixtures under all conditions examined.
      American cockroach extract controls were partly degraded at 10% to 25% glycerin,
      and cockroach allergen compatibilities were decreased significantly in mixtures
      with several fungal extracts at 25% glycerin. Mixing with other insects did not
      compromise the stability of American cockroach allergens at 25% to 50% glycerin.
      CONCLUSION: Aspergillus extracts exhibited favorable stabilities after mixing
      with other high-protease products. American cockroach extract potencies were
      unstable in less than 50% glycerin, even in the absence of other protease
      containing allergens, and were destabilized in mixtures with several fungal
      extracts. Addition of fungal and insect extracts to separate treatment vials or
      preparation of fungal-insect mixtures at elevated glycerin concentrations might
      be necessary to produce compatible patient formulations for allergen
      immunotherapy injections.

PMID- 25578249
TI  - Effect of cosmetic outcome on quality of life after breast cancer surgery.
AB  - PURPOSE: Studies regarding the effects of aesthetic outcomes after breast cancer
      surgery on quality of life (QoL) have yielded inconsistent results. This study
      analyzed the aesthetic outcomes and QoL of women who underwent breast conserving
      surgery (BCS) or total mastectomy with immediate reconstruction (TMIR) using
      objective and validated methods. PATIENTS AND METHODS: QoL questionnaires (EORTC
      QLQ-C30, BR23, and HADs) were administered at least 1 year after surgery and
      adjuvant therapy to 485 patients who underwent BCS, 46 who underwent TMIR, and 87
      who underwent total mastectomy (TM) without reconstruction. Aesthetic results
      were evaluated using BCCT.core software and by a panel of physicians. Patients'
      body image perception was assessed using the body image scale (BIS). RESULTS: QoL
      outcomes, including for social and role functioning, fatigue, pain, body image,
      and arm symptoms, were significantly better in the BCS and TMIR groups than in
      the TM group (p<0.05 each). BIS was significantly better in the BCS than in the
      TM or TMIR group (p<0.001 each). In the BCS and TMIR groups, general QoL factors
      were not significantly associated with objective cosmetic outcomes, except for
      body image in the QLQ-BR23. In contrast, patients with poorer BIS score reported
      lower QoL in almost all items of the QLQ-C30, BR23, and HADS (p<0.05 each).
      CONCLUSION: In conclusion, BCS and TMIR enhanced QoL compared with TM. Among BCS
      and TMIR patients, objectively measured cosmetic results did not affect general
      QoL. Self-perception of body image seems to be more important for QoL after
      breast cancer surgery.

PMID- 25578246
TI  - The infant microbiome development: mom matters.
AB  - The infant microbiome plays an essential role in human health and its assembly is
      determined by maternal-offspring exchanges of microbiota. This process is
      affected by several practices, including Cesarean section (C-section), perinatal
      antibiotics, and formula feeding, that have been linked to increased risks of
      metabolic and immune diseases. Here we review recent knowledge about the impacts
      on infant microbiome assembly, discuss preventive and restorative strategies to
      ameliorate the effects of these impacts, and highlight where research is needed
      to advance this field and improve the health of future generations. 

PMID- 25578250
TI  - Antecedents and consequences of cannabis use among racially diverse cannabis
      users: an analysis from Ecological Momentary Assessment.
AB  - BACKGROUND: Cannabis remains the most commonly used illicit substance and use
      rates are rising. Notably, the prevalence of cannabis use disorders (CUD) nearly
      equals that of other illicit substance use disorders combined. Thus, the present
      study aimed to identify cognitive, affective, and situational predictors and
      consequences of ad-lib cannabis use in a racially diverse sample. METHODS: The
      sample consisted of 93 current cannabis users (34.4% female; 57.1% non-Hispanic
      Caucasian), 87.1% of whom evinced a current CUD. Ecological Momentary Assessment
      was used to collect frequent ratings of cannabis withdrawal, craving, affect,
      cannabis use motives, and peer cannabis use over two weeks. Mixed effects linear
      models examined within- and between-day correlates and consequences of cannabis
      use. RESULTS: Withdrawal and craving were higher on cannabis use days than non
      use days. Withdrawal, craving, and positive and negative affect were higher
      immediately prior to cannabis use compared to non-use episodes. Withdrawal and
      craving were higher among those who subsequently used cannabis than those who did
      not. Cannabis use resulted in less subsequent withdrawal, craving, and negative
      affect. Enhancement and coping motives were the most common reasons cited for
      use. Withdrawal and negative affect were related to using cannabis for coping
      motives and social motives. Participants were most likely to use cannabis if
      others were using, and withdrawal and craving were greater in social situations
      when others were using. CONCLUSIONS: Data support the contention that cannabis
      withdrawal and craving and affect and peer use play important roles in the
      maintenance of cannabis use.

PMID- 25578251
TI  - Opioid substitution therapy is associated with increased detection of hepatitis C
      virus infection: a 15-year observational cohort study.
AB  - BACKGROUND: Strategies are needed to enhance screening of hepatitis C virus (HCV)
      infection among people who inject drugs to improve engagement in HCV treatment,
      and stem the growing burden of HCV-related morbidity and mortality. METHODS: We
      linked routinely collected data on enrolment in opioid substitution therapy (OST)
      and HCV notifications. We calculated rates of incident HCV notifications, and
      compared rates in and out of OST. RESULTS: Following adjustment for sex, age and
      calendar period, rates of incident HCV notification were significantly higher
      during periods of OST, compared to periods out of OST (adjusted incident rate
      ratio: 1.91; 95% confidence interval: 1.86, 1.97). This effect was seen across
      multiple treatment periods. CONCLUSIONS: HCV screening in OST settings increases
      detection of HCV infection among people who inject drugs.

PMID- 25578252
TI  - The interacting effect of depressive symptoms, gender, and distress tolerance on
      substance use problems among residential treatment-seeking substance users.
AB  - BACKGROUND: Depression is associated with substance use problems; however, the
      specific individual characteristics influencing this association are not well
      identified. Empirical evidence and theory suggest that gender and distress
      tolerance-defined behaviorally as an individual's ability to persist in goal
      directed behavior while experiencing negative affective states-are important
      underlying factors in this relationship. Hence, the purpose of the current study
      was to examine whether gender and distress tolerance moderate the relationship
      between depressive symptoms and substance use problems. METHODS: Participants
      included 189 substance users recruited from a residential substance abuse
      treatment center. The Short Inventory of Problems-Alcohol and Drugs scale was
      used to measure self-reported substance use problems. The Beck Depression
      Inventory was used to assess self-reported depressive symptoms. Gender was self
      reported, and distress tolerance was behaviorally indexed by the Computerized
      Paced Auditory Serial Addition Task. RESULTS: Hierarchical linear regression
      analysis indicated a significant three-way interaction of depressive symptoms,
      gender, and distress tolerance on substance use problems, adjusting for relevant
      demographic variables, anxiety symptoms, impulsivity, as well as DSM-IV
      psychiatric disorders. Probing of this three-way interaction demonstrated a
      significant positive association between depressive symptoms and substance use
      problems among females with low distress tolerance. CONCLUSION: Findings indicate
      that female treatment-seeking substance users with high levels of depressive
      symptoms exhibit greater substance use problems if they also evidence low
      distress tolerance. Study implications are discussed, including the development
      of prevention and intervention programs that target distress tolerance skills.

PMID- 25578253
TI  - Double trouble: Psychiatric comorbidity and opioid addiction-all-cause and cause
      specific mortality.
AB  - BACKGROUND: Opioid misusers have recognized high mortality but the influence of
      psychiatric comorbidity in excess cause-specific mortality is unclear. METHODS:
      Opioid use disorder (OUD) patients were identified in the South London and
      Maudsley Case Register. Deaths were identified through database linkage to the
      national mortality dataset. Standard mortality ratios were calculated to compare
      mortality risk with the general population. Cox and competing risk regression
      models were used to investigate the effect of psychiatric comorbidity and
      psychological health on all-cause and cause-specific mortality (respectively) in
      OUD patients. RESULTS: Of 4837 OUD patients, 176 had died. Mortality rates were
      substantially higher than the general population (SMR 4.23; 95%CI 3.63-4.90).
      Among those with OUD, comorbid personality disorder (PD) and comorbid alcohol use
      disorder (AUD) was associated with increased all-cause mortality in all models,
      including the fully adjusted model, controlling for socio-demographic factors,
      severity of drug use, risk behaviours and physical health (HR2.15, 95%CI 1.17
      3.95; HR2.28, 95%CI 1.54-3.36). AUD was associated with increased risk of fatal
      overdose (HR2.57, 95%CI 1.26-5.26) and hepatic-related deaths (HR7.26, 95%CI 2.79
      18.86). Individuals with OUD and comorbid PD had almost four times greater risk
      of liver related deaths compared to those without PD (HR3.76, 95%CI 1.21-11.74).
      Comorbid severe mental illness and poor psychological health were not associated
      with increased mortality. CONCLUSIONS: This study highlights the importance of
      assessment for PD and AUD in OUD patients in order to identify individuals at
      substantially elevated mortality risk to enable a more personalized approach to
      their medical care.

PMID- 25578254
TI  - The Physician Payments Sunshine Act: data evaluation regarding payments to
      ophthalmologists.
AB  - PURPOSE: To review data for ophthalmologists published online from the Physician
      Payments Sunshine Act. DESIGN: Retrospective data review using data acquired from
      a publicly available electronic database. METHODS: A database was downloaded from
      the Centers for Medicare and Medicaid Services website under Identified General
      Payments to Physicians and a primary specialty of ophthalmology. Basic
      statistical analysis was performed including mean, median, and range of payments
      for both single payments and per provider. MAIN OUTCOME MEASURES: Data summary by
      category of payment and geographic region and comparison with other surgical
      subspecialties. RESULTS: From August 1, 2013, through December 31, 2013, a total
      of 55 996 individual payments were reported to 9855 ophthalmologists for a total
      of $10 926 447. The mean amount received in a single payment was $195.13 (range,
      $0.04-$193 073). The mean amount received per physician identifier (ID) was $1108
      (range, $1-$397 849), and the median amount was $112.01. Consulting fees made up
      the largest percentage of fees. There was not a large difference in payments
      received by region. The mean payments for the subspecialties of dermatology,
      neurosurgery, orthopedic surgery, and urology ranged from $954 to $6980, and
      median payments in each field by physician ID ranged from $88 to $173.
      CONCLUSIONS: A large amount of data were released by the Centers for Medicare and
      Medicaid Services for the Physician Payment Sunshine Act. In ophthalmology, mean
      and median payments per physician did not vary greatly from other surgical
      subspecialties. Most single payments were less than $100, and most physicians
      received less than $500 in total payments. Payments for consulting made up the
      largest category of spending. How this affects patient perception, patient care,
      and medical costs warrants further study.

PMID- 25578255
TI  - Pigment epithelial detachment followed by retinal cystoid degeneration leads to
      vision loss in treatment of neovascular age-related macular degeneration.
AB  - PURPOSE: Intravitreal antiangiogenic therapy is the major therapeutic
      breakthrough in neovascular age-related macular degeneration (AMD). Optical
      coherence tomography (OCT) is the leading diagnostic tool, but solid criteria for
      optimal therapeutic outcomes are lacking. A comprehensive analysis of
      structure/function correlations using Food and Drug Administration- and European
      Medicines Agency-approved substances and fixed and flexible regimens was
      performed. DESIGN: Post hoc analysis of a prospective, randomized multicenter
      clinical trial including 189 study sites. PARTICIPANTS: A total of 1240 patients
      with active neovascular AMD. METHODS: Participants received intravitreal
      ranibizumab or aflibercept. A fixed regimen was used for 48 weeks followed by a
      flexible regimen until week 96. At monthly intervals, best-corrected visual
      acuity (BCVA) was measured and retinal morphology was assessed by standardized
      OCT, including intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment
      epithelial detachment (PED), presenting with a width >=400 MUm or a height of
      >=200 MUm. Results were correlated for each regimen, feature, and time. MAIN
      OUTCOME MEASURES: The BCVA outcomes in relation to retinal pathomorphology based
      on noninferiority for all treatment arms. RESULTS: In neovascular AMD, only IRC
      at baseline and persistent through week 12 had a negative impact on BCVA. With
      therapeutic intervention, exudative features such as IRC and SRF resolved rapidly
      in 74% of eyes, whereas PED responded only slowly with 38%. Independent of the
      type of regimen, fixed or flexible, retinal morphology correlated tightly with
      visual function. Intraretinal cysts consistently showed the lowest BCVA gains
      with either regimen or substance. With the switch from a fixed to a flexible pro
      re nata (PRN) regimen, progressive visual loss occurred exclusively in the group
      with primary PED presenting as the hallmark of neovascular activity and was
      induced by secondary formation of IRC in the neurosensory retina. CONCLUSIONS:
      The efficacy of antiangiogenic therapy in neovascular AMD is strongly determined
      by morphologic features. The subretinal pigment epithelium lesion underlying PED
      appears to be the primary indicator for progressive disease activity, whereas
      secondary cystoid degeneration is the most relevant imaging marker for visual
      function. Clinically, PED emerged as trigger for consecutive vision loss in PRN
      treatment.

PMID- 25578256
TI  - Detection of Mycobacterium tuberculosis genome in vitreous fluid of eyes with
      multifocal serpiginoid choroiditis.
AB  - PURPOSE: To compare 3 different molecular techniques to detect the Mycobacterium
      tuberculosis genome in vitreous fluid of eyes with multifocal serpiginoid
      choroiditis (MSC). DESIGN: Prospective, interventional case series. PARTICIPANTS:
      Eleven patients (11 eyes) with active MSC in at least 1 eye underwent diagnostic
      pars plana vitrectomy (PPV) between October 2012 and December 2013. METHODS:
      Vitreous fluid samples were subjected to multitargeted polymerase chain reaction
      (PCR) for a M. tuberculosis assay, the Gene Xpert MTB/RIF assay (Cepheid,
      Sunnyvale, CA), and a line probe assay (GenoType MTBDRplus; Hain Lifescience,
      GmbH, Nehren, Germany). The samples with positive results were subjected to rpoB
      gene sequencing to demonstrate rifampicin resistance. The clinical details,
      digital fundus imaging, and treatment details and outcomes also were noted. MAIN
      OUTCOME MEASURES: Detection of the M. tuberculosis genome and rifampicin
      resistance in the vitreous samples. RESULTS: Of the 11 eyes subjected to PPV, the
      multitargeted PCR results for tuberculosis were positive for 10 eyes, the
      MTBDRplus assay results were positive in 6 eyes, and the Gene Xpert MTB/RIF assay
      results were positive in 4 eyes. Rifampicin resistance was detected in 3 eyes by
      rpoB gene sequencing, in 3 eyes by the MTBDRplus assay, and in 1 eye by the Gene
      Xpert MTB/RIF assay. CONCLUSIONS: We detected the M. tuberculosis genome in the
      vitreous fluid of eyes with MSC using 3 different molecular techniques.
      Rifampicin resistance was detected for the first time in eyes with MSC.

PMID- 25578258
TI  - Chronic all-trans retinoic acid administration induces CRF over-expression
      accompanied by AVP up-regulation and multiple CRF-controlling receptors
      disturbance in the hypothalamus of rats.
AB  - Clinical reports suggest a potential link between excess retinoids and
      development of depression. Corticotropin-releasing factor (CRF) produced in the
      hypothalamic paraventricular nucleus (PVN) is considered the central driver of
      the hypothalamic-pituitary-adrenal (HPA) axis and plays a key role in the
      pathogenesis of depression. Although we had shown that chronic all-trans retinoic
      acid (ATRA) administration induced hypothalamic CRF over-expression and
      hyperactivity of HPA axis in rats, further insight into how ATRA modulate CRF
      expression is lacking. The activity of CRF neurons is under close control of
      vasopressinergic system and three-paired receptors (corticosteroid receptors, sex
      hormone receptors and CRF receptors). Here we show that ATRA-induced CRF over
      expression is accompanied by arginine-vasopressin (AVP) up-regulation and
      apparent gene expression disturbances of CRF-controlling receptors. ATRA was
      applied to rats by daily intraperitoneal injection for 6 weeks. Chronic ATRA
      treatment induced significantly increased expression of CRF and AVP in the PVN.
      Moreover, the transcript levels of CRF receptor 1 (CRFR1), estrogen receptor-beta
      (ERbeta) and mineralocorticoid receptor (MR), three genes involved in the
      activation of CRF neurons, were significantly increased in the hypothalamus, and
      the expression ratio of GRalpha/MR was markedly decreased. Correlation analysis
      indicated that the alteration of multiple CRF-controlling receptors is highly
      correlated with depression-related behaviors of rats in the forced swimming test.
      These findings support that in addition to the 'classic' retinoic acid receptor
      alpha-mediated transcriptional control of CRF expression, disruption in CRF
      modulating systems constitutes a novel pathway that underlies ATRA-induced HPA
      axis hyperactivity in vivo. 

PMID- 25578257
TI  - Type 1 diabetes alters astrocytic properties related with neurotransmitter
      supply, causing abnormal neuronal activities.
AB  - Glutamine synthetase (GS), an astrocytic protein in the brain, mediates the
      process by which glutamate (Glu) is transformed into glutamine (Gln) during Glu
      and gamma-aminobutyric acid (GABA) de novo synthesis. There are many types of
      neural complications related with those neurotransmitters in type 1 diabetes
      (T1D) patients, but there is little information about the change GS. Therefore,
      we examined changes in GS activity and expression, as well as the amount of Glu,
      Gln, and GABA in the brain of a T1D animal model. Using primary culture we found
      that glucose fluctuation caused glial fibrillary acidic protein (GFAP) and GS
      changes but constant high glucose level didn't. In T1D mouse, GS expression
      increased in the prefrontal cortex (PFC) and hippocampus (HI), but decreased GS
      activity was only observed in the HI whereas GFAP expression decreased in both
      regions. Gln increased in both regions, but Glu and GABA were only increased in
      the HI of T1D animals where GS activity decreased with higher reactive
      oxygen/nitrogen species. Collectively, low GS activity may be closely related
      with high levels of Glu and GABA in the HI of T1D brain, and this would result in
      abnormal neurotransmissions. 

PMID- 25578259
TI  - Differential role of AMPA receptors in mouse tests of antidepressant and
      anxiolytic action.
AB  - Depression and anxiety often co-occur, and conventional monoamine-facilitating
      antidepressants show efficacy against symptoms in both disorders. Rodent studies
      indicate that antidepressant effects of monoamine-based antidepressants involve
      increased alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid glutamate
      receptor (AMPAR) neurotransmission, and positive allosteric modulators (PAMs) at
      AMPARs produced antidepressant-like effects in rodents. While this suggests that
      increased AMPAR-mediated neurotransmission is beneficial in depression
      management, preclinical studies addressing AMPARs in relation to anxiety have
      given ambiguous results with both anxiolytic-like and anxiogenic-like effects
      observed after AMPAR blockade. This study systematically compared the effects of
      the AMPAR potentiator LY451646 and the AMPAR antagonist GYKI-53655 on depression
      related behaviour using the mouse forced swim (FST) and tail suspension tests
      (TST), and anxiety-related behaviour using the elevated zero maze (EZM), marble
      burying (MB) and novelty-induced hypophagia (NIH) tests. The serotonin-selective
      antidepressant citalopram was included for comparison. Due to the importance of
      AMPARs in learning and memory we also tested if GYKI-53655 disrupted performance
      in the V-maze test for attention-dependent behaviour, and the social transmission
      of food preference (STFP) test of long-term memory. LY451646 (3 mg/kg) showed an
      antidepressant-like profile in the FST and TST, and GYKI-53655 (>= 5 mg/kg) had a
      depressogenic-like effect in the TST but no effect in the FST. Conversely, GYKI
      53655 produced marked anxiolytic-like effects in the EZM (>= 2.5 mg/kg), MBT (>=
      2.5 mg/kg), and NIH tests (>= 5 mg/kg), while LY451646 (>= 3 mg/kg) increased
      anxiety-like behaviour in the EZM. Citalopram showed an antidepressant-like
      effect in the FST (>= 10 mg/kg), but not TST, an anxiolytic-like effect in the
      EZM (>= 3 mg/kg) and MB test (>= 2.5 mg/kg), and an anxiogenic-like effect in the
      NIH test (>= 30 mg/kg). GYKI-53655 did not affect cognitive performance in the V
      maze or STFP tests. Collectively, these findings suggest a differential role of
      AMPARs in depression and anxiety, with AMPAR activation promoting antidepressant
      responses and AMPAR inhibition promoting anxiolytic responses. The potential of
      AMPARs as a novel target in depression and anxiety pharmacotherapy is discussed.

PMID- 25578260
TI  - Macrophage activation and its role in repair and pathology after spinal cord
      injury.
AB  - The injured spinal cord does not heal properly. In contrast, tissue repair and
      functional recovery occur after skin or muscle injuries. The reason for this
      dichotomy in wound repair is unclear but inflammation, and specifically
      macrophage activation, likely plays a key role. Macrophages have the ability to
      promote the repair of injured tissue by regulating transitions through different
      phase of the healing response. In the current review we compare and contrast the
      healing and inflammatory responses between spinal cord injuries and tissues that
      undergo complete wound resolution. Through this comparison, we identify key
      macrophage phenotypes that are inaptly triggered or absent after spinal cord
      injury and discuss spinal cord stimuli that contribute to this maladaptive
      response. Sequential activation of classic, pro-inflammatory, M1 macrophages and
      alternatively activated, M2a, M2b, and M2c macrophages occurs during normal
      healing and facilitates transitions through the inflammatory, proliferative, and
      remodeling phases of repair. In contrast, in the injured spinal cord, pro
      inflammatory macrophages potentiate a prolonged inflammatory phase and remodeling
      is not properly initiated. The desynchronized macrophage activation after spinal
      cord injury is reminiscent of the inflammation present in chronic, non-healing
      wounds. By refining the role macrophages play in spinal cord injury repair we
      bring to light important areas for future neuroinflammation and neurotrauma
      research. This article is part of a Special Issue entitled SI: Spinal cord
      injury. 

PMID- 25578261
TI  - Assessment of adherence to treatment in patients with resistant hypertension
      using toxicological serum analysis. A subgroup evaluation of the RESIST-POL
      study.
AB  - INTRODUCTION: Nonadherence to antihypertensive therapy is one of the main causes
      of resistant hypertension. OBJECTIVES: The aim of our study was to evaluate
      adherence to therapy in patients with resistant hypertension by determining serum
      antihypertensive drug levels with the use of liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). PATIENTS AND METHODS: The study included 36 patients
      with primary resistant hypertension selected from the RESIST-POL study (23 men
      and 13 women; mean age, 52.5 +/-9.1 years; range, 22-67 years; mean number of
      antihypertensive drugs, 5.3 +/-1.4), who met all 3 inclusion criteria: use of >=4
      antihypertensive drugs; average daytime ambulatory systolic blood pressure >=140
      mmHg; one of the clinical features suggesting nonadherence. All patients had
      their serum drug levels assessed using LC-MS/MS. Patients in whom the serum level
      of at least 1 drug was below the limit of quantification for the method used were
      regarded as nonadherent. RESULTS: Of all study patients, nonadherence was
      observed in 31 patients (86.1%), and none of the prescribed drugs was detected
      (complete nonadherence) in 5 patients (13.9%). In 26 patients (72.2%), at least 1
      of the prescribed drugs could not be detected (partial nonadherence).
      CONCLUSIONS: In our study, we documented a surprisingly low adherence to
      antihypertensive treatment in patients with resistant hypertension. Our results
      suggest that, particularly in those patients, the analysis of serum
      antihypertensive drug levels using LC-MS/MS might allow to avoid a comprehensive
      and costly diagnostic work-up including biochemical and imaging studies.

PMID- 25578262
TI  - Sputum induction is a safe procedure to use in prisoners and MGIT is the best
      culture method to diagnose tuberculosis in prisons: a cohort study.
AB  - OBJECTIVES: To evaluate the concordance and safety of induced sputum (IS) and
      spontaneous sputum (SS), and estimate concordance and time to detection of M.
      tuberculosis between Lowenstein-Jensen (LJ), thin-layer agar (TLA), and the
      Mycobacteria Growth Indicator Tube system (MGIT). METHODS: This was a cohort
      study. Prisoners with pulmonary tuberculosis (PTB) were followed for 2 years. At
      baseline and every follow-up visit, three sputum samples were taken on
      consecutive days (one IS and two SS) and adverse events occurring before, during,
      and 30 min after IS were registered. All sputum samples were stained with
      auramine and cultured in LJ, TLA (to test resistance), and MGIT. RESULTS: Five
      hundred eighty-six IS and 532 SS were performed on 64 PTB patients.
      Breathlessness (1.6%), cough (1.2%), hemoptysis (0.3%), and cyanosis (0.2%) were
      the only complications. Concordance between IS and SS was 0.78 (95% confidence
      interval 0.69-0.87); 11 positive cultures from IS samples were negative in SS,
      and 11 positive cultures from SS samples were negative in IS. One hundred seventy
      eight cultures were positive by any technique: MGIT 95%, LJ 73%, and TLA 57%.
      Time to detection of M. tuberculosis in LJ, TLA, and MGIT was 31, 18, and 11
      days, respectively. CONCLUSIONS: The IS procedure is safe in prisons. The MGIT
      system is better and faster than LJ and TLA in the diagnosis of M. tuberculosis.

PMID- 25578263
TI  - Misidentification of Streptococcus uberis as a human pathogen: a case report and
      literature review.
AB  - Streptococcus uberis is an environmental bacterium responsible for bovine
      mastitis. It is occasionally described as a human pathogen, though in most cases
      the identification was based on biochemical phenotyping techniques. This report
      shows that the biochemical phenotyping may incorrectly identify Enterococcus
      faecium as S. uberis. 

PMID- 25578264
TI  - An outbreak of Burkholderia stabilis colonization in a nasal ward.
AB  - OBJECTIVE: The aim of this study was to describe an outbreak of Burkholderia
      stabilis colonization among patients in a nasal ward. METHODS: Multilocus
      sequence typing (MLST) was used for the molecular typing of B. stabilis isolates.
      Microbiological records were reviewed to delineate the colonization outbreak
      period. One hundred seventy-one cultures of environment and equipment samples
      from the nasal ward were performed to trace the source of contamination.
      Infection control measures were taken in order to end the outbreak. RESULTS: All
      B. stabilis isolates were identified as a new MLST type, ST821. A total of 53
      patients carried this B. stabilis in the nasal ward between March and September
      2013, which was defined as the outbreak period. The source of the colonization
      was not determined because all environment cultures were negative for
      Burkholderia cepacia complex. No further B. stabilis carriers have been found in
      the ward since the implementation of interventions. CONCLUSIONS: Attention must
      be paid to asymptomatic colonization in order to identify outbreaks early.

PMID- 25578266
TI  - A note on this special issue.

PMID- 25578265
TI  - The mast cell stabilizer sodium cromoglycate reduces histamine release and status
      epilepticus-induced neuronal damage in the rat hippocampus.
AB  - Experiments were designed to evaluate changes in the histamine release, mast cell
      number and neuronal damage in hippocampus induced by status epilepticus. We also
      evaluated if sodium cromoglycate, a stabilizer of mast cells with a possible
      stabilizing effect on the membrane of neurons, was able to prevent the release of
      histamine, gamma-aminobutyric acid (GABA) and glutamate during the status
      epilepticus. During microdialysis experiments, rats were treated with saline (SS
      SE) or sodium cromoglycate (CG-SE) and 30 min later received the administration
      of pilocarpine to induce status epilepticus. Twenty-four hours after the status
      epilepticus, the brains were used to determine the neuronal damage and the number
      of mast cells in hippocampus. During the status epilepticus, SS-SE group showed
      an enhanced release of histamine (138.5%, p = 0.005), GABA (331 +/- 91%, p <=
      0.001) and glutamate (467%, p <= 0.001), even after diazepam administration. One
      day after the status epilepticus, SS-SE group demonstrated increased number of
      mast cells in Stratum pyramidale of CA1 (88%, p < 0.001) and neuronal damage in
      dentate gyrus, CA1 and CA3. In contrast to SS-SE group, rats from the CG-SE group
      showed increased latency to the establishment of the status epilepticus (p =
      0.048), absence of wet-dog shakes, reduced histamine (but not GABA and glutamate)
      release, lower number of mast cells (p = 0.008) and reduced neuronal damage in
      hippocampus. Our data revealed that histamine, possibly from mast cells, is
      released in hippocampus during the status epilepticus. This effect may be
      involved in the subsequent neuronal damage and is diminished with sodium
      cromoglycate pretreatment.

PMID- 25578267
TI  - It is easy to get huge candidate gene lists for plant metabolism now, but how to
      get beyond?

PMID- 25578269
TI  - Multifaceted regulations of gateway enzyme phenylalanine ammonia-lyase in the
      biosynthesis of phenylpropanoids.
AB  - Phenylpropanoid biosynthesis in plants engenders a vast variety of aromatic
      metabolites critically important for their growth, development, and environmental
      adaptation. Some of these aromatic compounds have high economic value.
      Phenylalanine ammonia-lyase (PAL) is the first committed enzyme in the pathway;
      it diverts the central flux of carbon from the primary metabolism to the
      synthesis of myriad phenolics. Over the decades, many studies have shown that
      exquisite regulatory mechanisms at multiple levels control the transcription and
      the enzymatic activity of PALs. In this review, a current overview of our
      understanding of the complicated regulatory mechanisms governing the activity of
      PAL is presented; recent progress in unraveling its post-translational
      modifications, its metabolite feedback regulation, and its enzyme organization is
      highlighted. 

PMID- 25578270
TI  - Regulation of carotenoid metabolism in tomato.
AB  - Carotenoids serve diverse functions in vastly different organisms that both
      produce and consume them. Enhanced carotenoid accumulation is of great importance
      in the visual and functional properties of fruits and vegetables. Significant
      progress has been achieved in recent years in our understanding of carotenoid
      biosynthesis in tomato (Solanum lycopersicum) using biochemical and genetics
      approaches. The carotenoid metabolic network is temporally and spatially
      controlled, and plants have evolved strategic tactics to regulate carotenoid
      metabolism in response to various developmental and environmental factors. In
      this review, we summarize the current status of studies on transcription factors
      and phytohormones that regulate carotenoid biosynthesis, catabolism, and storage
      capacity in plastids, as well as the responses of carotenoid metabolism to
      environmental cues in tomato fruits. Transcription factors function either in
      cooperation with or independently of phytohormone signaling to regulate
      carotenoid metabolism, providing novel approaches for metabolic engineering of
      carotenoid composition and content in tomato. 

PMID- 25578268
TI  - The application of synthetic biology to elucidation of plant mono-, sesqui-, and
      diterpenoid metabolism.
AB  - Plants synthesize a huge variety of terpenoid natural products, including
      photosynthetic pigments, signaling molecules, and defensive substances. These are
      often produced as complex mixtures, presumably shaped by selective pressure over
      evolutionary timescales, some of which have been found to have pharmaceutical and
      other industrial uses. Elucidation of the relevant biosynthetic pathways can
      provide increased access (e.g., via molecular breeding or metabolic engineering)
      and enable reverse genetic approaches toward understanding the physiological role
      of these natural products in plants as well. While such information can be
      obtained via a variety of approaches, this review describes the emerging use of
      synthetic biology to recombinantly reconstitute plant terpenoid biosynthetic
      pathways in heterologous host organisms as a functional discovery tool, with a
      particular focus on incorporation of the historically problematic cytochrome P450
      mono-oxygenases. Also falling under the synthetic biology rubric and discussed
      here is the nascent application of genome-editing tools to probe physiological
      function. 

PMID- 25578271
TI  - Vanillin-bioconversion and bioengineering of the most popular plant flavor and
      its de novo biosynthesis in the vanilla orchid.
AB  - In recent years, biotechnology-derived production of flavors and fragrances has
      expanded rapidly. The world's most popular flavor, vanillin, is no exception.
      This review outlines the current state of biotechnology-based vanillin synthesis
      with the use of ferulic acid, eugenol, and glucose as substrates and bacteria,
      fungi, and yeasts as microbial production hosts. The de novo biosynthetic pathway
      of vanillin in the vanilla orchid and the possible applied uses of this new
      knowledge in the biotechnology-derived and pod-based vanillin industries are also
      highlighted.

PMID- 25578272
TI  - Using metabolomic approaches to explore chemical diversity in rice.
AB  - Rice (Oryza sativa) is an excellent resource; it comprises 25% of the total
      caloric intake of the world's population, and rice plants yield many types of
      bioactive compounds. To determine the number of metabolites in rice and their
      chemical diversity, the metabolite composition of cultivated rice has been
      investigated with analytical techniques such as mass spectrometry (MS) and/or
      nuclear magnetic resonance spectroscopy and rice metabolite databases have been
      constructed. This review summarizes current knowledge on metabolites in rice
      including sugars, amino and organic acids, aromatic compounds, and phytohormones
      detected by gas chromatography-MS, liquid chromatography-MS, and capillary
      electrophoresis-MS. The biological properties and the activities of polar and
      nonpolar metabolites produced by rice plants are also presented. Challenges in
      the estimation of the structure(s) of unknown metabolites by metabolomic
      approaches are introduced and discussed. Lastly, examples are presented of the
      successful application of metabolite profiling of rice to characterize the
      gene(s) that are potentially critical for improving its quality by combining
      metabolite quantitative trait loci analysis and to identify potential metabolite
      biomarkers that play a critical role when rice is grown under abiotic stress
      conditions. 

PMID- 25578273
TI  - Carotenoid metabolism in plants.
AB  - Carotenoids are mostly C40 terpenoids, a class of hydrocarbons that participate
      in various biological processes in plants, such as photosynthesis,
      photomorphogenesis, photoprotection, and development. Carotenoids also serve as
      precursors for two plant hormones and a diverse set of apocarotenoids. They are
      colorants and critical components of the human diet as antioxidants and
      provitamin A. In this review, we summarize current knowledge of the genes and
      enzymes involved in carotenoid metabolism and describe recent progress in
      understanding the regulatory mechanisms underlying carotenoid accumulation. The
      importance of the specific location of carotenoid enzyme metabolons and plastid
      types as well as of carotenoid-derived signals is discussed. 

PMID- 25578274
TI  - A familiar ring to it: biosynthesis of plant benzoic acids.
AB  - Plant benzoic acids (BAs) are building blocks or important structural elements
      for numerous primary and specialized metabolites, including plant hormones,
      cofactors, defense compounds, and attractants for pollinators and seed
      dispersers. Many natural products derived from plant BAs or containing
      benzoyl/benzyl moieties are also of medicinal or nutritional value to humans.
      Biosynthesis of BAs in plants is a network involving parallel and intersecting
      pathways spread across multiple subcellular compartments. In this review, a
      current overview on the metabolism of plant BAs is presented with a focus on the
      recent progress made on isolation and functional characterization of genes
      encoding biosynthetic enzymes and intracellular transporters. In addition,
      approaches for deciphering the complex interactions between pathways of the BAs
      network are discussed. 

PMID- 25578275
TI  - Progressive regulation of sesquiterpene biosynthesis in Arabidopsis and Patchouli
      (Pogostemon cablin) by the miR156-targeted SPL transcription factors.
AB  - Plant metabolites vary at different stages of their life cycle. Although it is
      well documented that environmental factors stimulate biosynthesis of secondary
      metabolites, the regulation by endogenous developmental cues remains poorly
      understood. The microRNA156 (miR156)-targeted squamosa promoter binding protein
      like (SPL) factors function as a major age cue in regulating developmental phase
      transition and flowering. We show here that the miR156-targeted SPL transcription
      factor plays an important role in the spatiotemporal regulation of sesquiterpene
      biosynthesis. In Arabidopsis thaliana, the miR156-SPL module regulates the
      formation of (E)-beta-caryophyllene in the flowering stage through modulating
      expression of the sesquiterpene synthase gene TPS21. We demonstrated that SPL9
      directly binds to TPS21 promoter and activates its expression. In the perennial
      fragrant herb Pogostemon cablin, the accumulation of patchouli oil, largely
      composed of sesquiterpenes dominated by (-)-patchoulol, is also age-regulated,
      and the SPL promotes biosynthesis of sesquiterpenes in elder plants by
      upregulating patchoulol synthase (PatPTS) gene expression. As miR156-SPLs are
      highly conserved in plants, our finding not only uncovers a molecular link
      between developmental timing and sesquiterpene production but also suggests a new
      strategy to engineer plants for accelerated growth with enhanced production of
      terpenoids.

PMID- 25578276
TI  - Spatiotemporal distribution of phenolamides and the genetics of natural variation
      of hydroxycinnamoyl spermidine in rice.
AB  - Phenolamides constitute a diverse class of secondary metabolites that are found
      ubiquitously in plants and have been implicated to play an important role in a
      wide range of biological processes, such as plant development and defense.
      However, spatiotemporal accumulation patterns of phenolamides in rice, one of the
      most important crops, are not available, and no gene responsible for phenolamide
      biosynthesis has been identified in this species. In this study, we report the
      comprehensive metabolic profiling and natural variation analysis of phenolamides
      in a collection of rice germplasm using a liquid chromatography-mass spectrometry
      based targeted metabolomics method. Spatiotemporal controlled accumulations were
      observed for most phenolamides, together with their differential accumulations
      between the two major subspecies of rice. Further metabolic genome-wide
      association study (mGWAS) in rice leaf and in vivo metabolic analysis of the
      transgenic plants identified Os12g27220 and Os12g27254 as two spermidine
      hydroxycinnamoyl transferases that might underlie the natural variation of levels
      of spermidine conjugates in rice. Our work demonstrates that gene-to-metabolite
      analysis by mGWAS provides a useful tool for functional gene identification and
      omics-based crop genetic improvement.

PMID- 25578277
TI  - Unraveling the triterpenoid saponin biosynthesis of the African shrub Maesa
      lanceolata.
AB  - Maesasaponins produced by the African shrub Maesa lanceolata are oleanane-type
      saponins with diverse biological activities. Through a combination of transcript
      profiling of methyl jasmonate-elicited M. lanceolata shoot cultures, functional
      analysis in transgenic M. lanceolata plants and the heterologous hosts Medicago
      truncatula and Saccharomyces cerevisiae, we identified three maesaponin
      biosynthesis genes. These include a beta-amyrin synthase and two cytochrome
      P450s, CYP716A75 and CYP87D16, which catalyze the C-28 and C-16alpha oxidations
      of beta-amyrin, respectively.

PMID- 25578279
TI  - Divergence in the enzymatic activities of a tomato and Solanum pennellii alcohol
      acyltransferase impacts fruit volatile ester composition.
AB  - Tomato fruits accumulate a diverse set of volatiles including multiple esters.
      The content of ester volatiles is relatively low in tomato fruits (Solanum
      lycopersicum) and far more abundant in the closely related species Solanum
      pennellii. There are also qualitative variations in ester content between the two
      species. We have previously shown that high expression of a non-specific esterase
      is critical for the low overall ester content of S. lycopersicum fruit relative
      to S. pennellii fruit. Here, we show that qualitative differences in ester
      composition are the consequence of divergence in enzymatic activity of a ripening
      related alcohol acyltransferase (AAT1). The S. pennellii AAT1 is more efficient
      than the tomato AAT1 for all the alcohols tested. The two enzymes have
      differences in their substrate preferences that explain the variations observed
      in the volatiles. The results illustrate how two related species have evolved to
      precisely adjust their volatile content by modulating the balance of the
      synthesis and degradation of esters.

PMID- 25578278
TI  - Iridoid synthase activity is common among the plant progesterone 5beta-reductase
      family.
AB  - Catharanthus roseus, the Madagascar periwinkle, synthesizes bioactive
      monoterpenoid indole alkaloids, including the anti-cancer drugs vinblastine and
      vincristine. The monoterpenoid branch of the alkaloid pathway leads to the
      secoiridoid secologanin and involves the enzyme iridoid synthase (IS), a member
      of the progesterone 5beta-reductase (P5betaR) family. IS reduces 8-oxogeranial to
      iridodial. Through transcriptome mining, we show that IS belongs to a family of
      six C. roseus P5betaR genes. Characterization of recombinant CrP5betaR proteins
      demonstrates that all but CrP5betaR3 can reduce progesterone and thus can be
      classified as P5betaRs. Three of them, namely CrP5betaR1, CrP5betaR2, and
      CrP5betaR4, can also reduce 8-oxogeranial, pointing to a possible redundancy with
      IS (corresponding to CrP5betaR5) in secoiridoid synthesis. In-depth functional
      analysis by subcellular protein localization, gene expression analysis, in situ
      hybridization, and virus-induced gene silencing indicate that besides IS,
      CrP5betaR4 may also participate in secoiridoid biosynthesis. We cloned a set of
      P5betaR genes from angiosperm plant species not known to produce iridoids and
      demonstrate that the corresponding recombinant proteins are also capable of using
      8-oxogeranial as a substrate. This suggests that IS activity is intrinsic to
      angiosperm P5betaR proteins and has evolved early during evolution.

PMID- 25578280
TI  - A basic leucine zipper transcription factor, AabZIP1, connects abscisic acid
      signaling with artemisinin biosynthesis in Artemisia annua.
AB  - Artemisinin is a sesquiterpenoid especially synthesized in the Chinese herbal
      plant, Artemisia annua, which is widely used in the treatment of malaria.
      Artemisinin accumulation can be enhanced by exogenous abscisic acid (ABA)
      treatment. However, it is not known how ABA signaling regulates artemisinin
      biosynthesis. A global expression profile and phylogenetic analysis as well as
      the dual-LUC screening revealed that a basic leucine zipper family transcription
      factor from A. annua (namely AabZIP1) was involved in ABA signaling to regulate
      artemisinin biosynthesis. AabZIP1 had a higher expression level in the
      inflorescences than in other tissues; ABA treatment, drought, and salt stress
      strongly induced the expression of AabZIP1. Yeast one-hybrid assay and
      electrophoretic mobility shift assay (EMSA) showed that AabZIP1 bound to the ABA
      responsive elements (ABRE) in the promoter regions of the amorpha-4,11-diene
      synthase (ADS) gene and CYP71AV1, which are two key structural genes of the
      artemisinin biosynthetic pathway. A mutagenesis assay showed that the C1 domain
      in the N-terminus of AabZIP1 was important for its transactivation activity.
      Furthermore, the activation of ADS and CYP71AV1 promoters by AabZIP1 was enhanced
      by ABA treatment in transient dual-LUC analysis. The AabZIP1 variant with C1
      domain deletion lost the ability to activate ADS and CYP71AV1 promoters
      regardless of ABA treatment. Notably, overexpression of AabZIP1 in A. annua
      resulted in significantly increased accumulation of artemisinin. Our results
      indicate that ABA promotes artemisinin biosynthesis, likely through 1 activation
      of ADS and CYP71AV1 expression by AabZIP in A. annua. Meanwhile, our findings
      reveal the potential value of AabZIP1 in genetic engineering of artemisinin
      production.

PMID- 25578281
TI  - 4-Coumaroyl and caffeoyl shikimic acids inhibit 4-coumaric acid:coenzyme A
      ligases and modulate metabolic flux for 3-hydroxylation in monolignol
      biosynthesis of Populus trichocarpa.
AB  - Downregulation of 4-coumaric acid:coenzyme A ligase (4CL) can reduce lignin
      content in a number of plant species. In lignin precursor (monolignol)
      biosynthesis during stem wood formation in Populus trichocarpa, two enzymes,
      Ptr4CL3 and Ptr4CL5, catalyze the coenzyme A (CoA) ligation of 4-coumaric acid to
      4-coumaroyl-CoA and caffeic acid to caffeoyl-CoA. CoA ligation of 4-coumaric acid
      is essential for the 3-hydroxylation of 4-coumaroyl shikimic acid. This
      hydroxylation results from sequential reactions of 4-hydroxycinnamoyl
      CoA:shikimic acid hydroxycinnamoyl transferases (PtrHCT1 and PtrHCT6) and 4
      coumaric acid 3-hydroxylase 3 (PtrC3H3). Alternatively, 3-hydroxylation of 4
      coumaric acid to caffeic acid may occur through an enzyme complex of cinnamic
      acid 4-hydroxylase 1 and 2 (PtrC4H1 and PtrC4H2) and PtrC3H3. We found that 4
      coumaroyl and caffeoyl shikimic acids are inhibitors of Ptr4CL3 and Ptr4CL5. 4
      Coumaroyl shikimic acid strongly inhibits the formation of 4-coumaroyl-CoA and
      caffeoyl-CoA. Caffeoyl shikimic acid inhibits only the formation of 4-coumaroyl
      CoA. 4-Coumaroyl and caffeoyl shikimic acids both act as competitive and
      uncompetitive inhibitors. Metabolic flux in wild-type and PtrC3H3 downregulated
      P. trichocarpa transgenics has been estimated by absolute protein and metabolite
      quantification based on liquid chromatography-tandem mass spectrometry, mass
      action kinetics, and inhibition equations. Inhibition by 4-coumaroyl and caffeoyl
      shikimic acids may play significant regulatory roles when these inhibitors
      accumulate. 

PMID- 25578282
TI  - Multiple levels of regulation determine monoterpenoid essential oil compositional
      variation in the mint family.

PMID- 25578283
TI  - Evolutionary theory as a tool for predicting extinction risk.
AB  - Timely and proactive wildlife conservation requires strategies for determining
      which species are most at the greatest threat of extinction. Here, we suggest
      that evolutionary theory, particularly the concept of specialization, can be a
      useful tool to inform such assessments and may greatly aid in our ability to
      predict the vulnerabilities of species to anthropogenic impacts. 

PMID- 25578284
TI  - The cost of an Ebola case.
AB  - As the most recent outbreak of Ebola virus disease (EVD) in West Africa continues
      to grow since its initial recognition as a Public Health Emergency of
      International Concern, an unanswered question is what is the cost of a case of
      Ebola? Understanding this cost will help decision makers better understand the
      impact of each case of EVD, benchmark this against that of other diseases,
      prioritize which cases may require response, and begin to estimate the cost of
      Ebola outbreaks. To date, the scientific literature has not characterized this
      cost per case. Therefore, we developed a mathematical model to estimate the cost
      of an EVD case from the provider and societal perspectives in the three most
      affected countries of Guinea, Liberia, and Sierra Leone. Our model estimates the
      total societal cost of an EVD case with full recovery ranges from $480 to $912,
      while that of an EVD case not surviving ranges from $5929 to $18 929, varying by
      age and country. Therefore, as of 10 December 2014, the estimated total societal
      costs of all reported EVD cases in these three countries range from $82 to
      potentially over $356 million. 

PMID- 25578285
TI  - Brucellosis update in Libya and regional prospective.
AB  - Brucellosis is a global bacterial zoonosis responsible for high morbidity in
      humans and significant livestock economic losses. While brucellosis remains a
      public health concern worldwide, its global geographic distribution is variable,
      largely due to different management schemes; however, paucity of information
      renders the status of brucellosis unclear and incomplete in many countries,
      especially those with low income and under-developed infrastructure. This short
      article summarizes and discusses recent important updates on brucellosis from the
      North African countries, with a particular brief emphasis on the current status
      and recent updates in Libya. 

PMID- 25578286
TI  - Laparoscopic diverted resleeve with ileal transposition for failed laparoscopic
      sleeve gastrectomy: a case report.
AB  - Laparoscopic sleeve gastrectomy (LSG) recently gained popularity for the
      treatment of obesity and related co-morbidities. With the increasing number of
      bariatric operations, the requirement for redo or revision bariatric surgery
      seems to be increasing. In the present case, a 50-year-old female patient with
      failed LSG who underwent laparoscopic resleeve, duodenal diversion, and ileal
      transposition is presented. Her metabolic and biochemical parameters were found
      to be improved significantly after 18 months. To the best of our knowledge, this
      is the first report of a case treated with this method in the literature. 

PMID- 25578287
TI  - Comment on: Visceral fat area as a new predictor of short-term diabetes remission
      after Roux-en-Y gastric bypass surgery in Chinese patients with a body mass index
      less than 35 kg/m2.

PMID- 25578288
TI  - Mitochondrial proteases and protein quality control in ageing and longevity.
AB  - Mitochondria have been implicated in the ageing process and the lifespan
      modulation of model organisms. Mitochondria are the main providers of energy in
      eukaryotic cells but also represent both a major source of reactive oxygen
      species and targets for protein oxidative damage. Since protein damage can impair
      mitochondrial function, mitochondrial proteases are critically important for
      protein maintenance and elimination of oxidized protein. In the mitochondrial
      matrix, protein quality control is mainly achieved by the Lon and Clp proteases
      which are also key players in damaged mitochondrial proteins degradation.
      Accumulation of damaged macromolecules resulting from oxidative stress and
      failure of protein maintenance constitutes a hallmark of cellular and organismal
      ageing and is believed to participate to the age-related decline of cellular
      function. Hence, age-related impairment of mitochondrial protein quality control
      may therefore contribute to the age-associated build-up of oxidized protein and
      alterations of mitochondrial redox and protein homeostasis. 

PMID- 25578289
TI  - Impact of mild cognitive impairment on outcome following deep brain stimulation
      surgery for Parkinson's disease.
AB  - INTRODUCTION: Unlike dementia, the effect of mild cognitive impairment (MCI) on
      outcomes after deep brain stimulation (DBS) in Parkinson's disease (PD) is less
      clear. We aimed to examine the effect of MCI on short- and long-term DBS
      outcomes. METHODS: To study the effect of MCI type, cognitive domains (attention,
      language, visuospatial, memory, executive function), and Dementia Rating Scale
      (DRS) score on immediate postoperative outcomes (postoperative confusion,
      hospitalization days), PD patients who underwent DBS at our Center from 2006 to
      2011 were analyzed. To determine cognitive predictors of intermediate (6-month)
      and long-term (1-year) post-operative outcomes, the changes in functional and
      quality-of-life (QOL) scores were analyzed in a smaller group with available
      preoperative health status measures. RESULTS: We identified 130 patients [71%
      male, mean age: 63 +/- 9.1, mean PD duration: 10.7 +/- 5.1]. At preoperative
      assessment, 60% of patients had multiple-domain MCI, 21% had single-domain MCI,
      and 19% had normal cognition. MCI presence and type as well as DRS performance
      did not affect immediate outcomes. Attention impairment predicted longer
      postoperative hospitalization (P = 0.0015) and showed a trend towards occurrence
      of postoperative confusion (P = 0.089). For intermediate and long-term outcomes
      we identified 56 patients [73.2% male, mean age: 61.3 +/- 9.6, mean PD duration:
      10.6 +/- 4.7]. Visuospatial impairment showed a trend towards less improvement in
      6-month functional score (P = 0.0652), and 1-year QOL score (P = 0.0517).
      CONCLUSION: The presence of MCI did not affect DBS outcomes. However, the types
      of impaired domains were more detrimental. Detailed cognitive testing can help
      stratify low- and high-risk patients based on their pattern of cognitive
      dysfunction.

PMID- 25578291
TI  - Ultra-early MRI in assessment of neurological prognosis in cardiac arrest
      survivors.

PMID- 25578290
TI  - 24 h Levodopa-carbidopa intestinal gel may reduce falls and "unresponsive"
      freezing of gait in Parkinson's disease.
AB  - OBJECTIVE: We report a prospective, open label study of 24 h levodopa-carbidopa
      intestinal gel (LCIG) as treatment for levodopa "unresponsive" freezing of gait
      (FOG) associated with Parkinson's disease. METHOD: 5 patients with disabling FOG,
      documented as being levodopa "unresponsive", were commenced on continuous 24 h
      infusion LCIG therapy with the night-time rate at 50-80% of the daytime infusion
      rate. Patients underwent baseline, 3 and 6 month gait assessments, documentation
      of their falls frequency and completed FOG questionnaires. RESULT: Median 360
      degrees  turn time improved by 54%, fall frequency score reduced from 3 to 0 at 6
      months, FOG questionnaire score improved by 14% and Timed Up- and -Go 8 m walk
      was unchanged. CONCLUSION: 24 h LCIG therapy may reduce levodopa "unresponsive"
      FOG and associated falls. A larger prospective study is needed for confirmation.

PMID- 25578292
TI  - Factors affecting attitudes and barriers to a medical emergency team among nurses
      and medical doctors: a multi-centre survey.
AB  - AIM: To identify factors underlying attitudes towards the medical emergency team
      (MET) and barriers to its utilisation among ward nurses and physicians. METHODS:
      Multicentre survey using an anonymous questionnaire in hospitals with a fully
      operational MET system in the Piedmont Region, Italy. Response to questions was
      scored on a 5-point Likert-type agreement scale. Dichotomised results were
      included in a logistic regression model. RESULTS: Among 2279 staff members who
      were contacted, 1812 (79.6%) completed the survey. The vast majority of
      respondents valued the MET. Working in a surgical vs. medical ward and having
      participated in either the MET educational programme (METal course) or MET
      interventions were associated with better acceptance of the MET system.
      Reluctance by nurses to call the covering doctor first instead of the MET for
      deteriorating patients (62%) was significantly less likely in those working in
      surgical vs. medical wards or having a higher seniority or a METal certification
      (OR 0.51 [0.4-0.65], 0.69 [0.47-0.99], and 0.6 [0.46-0.79], respectively).
      Reluctance to call the MET in a patient fulfilling calling criteria (21%), was
      less likely to occur in medical doctors vs. nurses and in surgical vs. medical
      ward staff, and it was unaffected by the METal certification. CONCLUSIONS: The
      MET was well accepted in participating hospitals. Nurse referral to the covering
      physician was the major barrier to MET activation. Medical status, working in
      surgical vs. medical wards, seniority and participation in the METal educational
      programme were associated with lower likelihood of showing barriers to MET
      activation.

PMID- 25578293
TI  - Online crowdsourcing for efficient rating of speech: a validation study.
AB  - Blinded listener ratings are essential for valid assessment of interventions for
      speech disorders, but collecting these ratings can be time-intensive and costly.
      This study evaluated the validity of speech ratings obtained through online
      crowdsourcing, a potentially more efficient approach. 100 words from children
      with /r/ misarticulation were electronically presented for binary rating by 35
      phonetically trained listeners and 205 naive listeners recruited through the
      Amazon Mechanical Turk (AMT) crowdsourcing platform. Bootstrapping was used to
      compare different-sized samples of AMT listeners against a "gold standard" (mode
      across all trained listeners) and an "industry standard" (mode across
      bootstrapped samples of three trained listeners). There was strong overall
      agreement between trained and AMT listeners. The "industry standard" level of
      performance was matched by bootstrapped samples with n = 9 AMT listeners. These
      results support the hypothesis that valid ratings of speech data can be obtained
      in an efficient manner through AMT. Researchers in communication disorders could
      benefit from increased awareness of this method. LEARNING OUTCOMES: Readers will
      be able to (a) discuss advantages and disadvantages of data collection through
      the crowdsourcing platform Amazon Mechanical Turk (AMT), (b) describe the results
      of a validity study comparing samples of AMT listeners versus phonetically
      trained listeners in a speech-rating task.

PMID- 25578294
TI  - Enriched environment restricted to gestation accelerates the development of
      sensory and motor circuits in the rat pup.
AB  - The effects of stimulating environments on the neural plasticity of the adult
      brain have been well explored; however, how an enriched environment (EE) affects
      the mother-fetus interaction is poorly understood. We hypothesized that an
      enriched environment restricted to pregnancy will succeed in accelerating the
      development of sensory and motor circuits in the offspring. Pregnant Wistar rats
      were maintained either under a standard condition - two animals per standard cage
      or an enriched environment - eight subjects in larger cages with different
      physical configurations-. After birth, litters from both groups (n=16 per group)
      were cross-fostered with mothers that were simultaneously maintained under
      standard environment during pregnancy. Sensory and motor development were studied
      in the pups of both groups with a battery of reflex and physical tests. Auditory
      and gait reflexes appeared two days earlier in the offspring of EE rats as
      compared to control subjects (p<0.05). In addition, EE pups displayed a better
      performance in righting reflex, inclined board and geotaxis tests (p<0.05).
      Differences were found even three weeks after birth. We conclude that EE limited
      to the phase of pregnancy stimulates the development of pups inutero so that they
      are born with a higher grade of development. 

PMID- 25578296
TI  - Tribute to: Dr. Greg A. Gerhardt, Ph.D.: Journal of Neuroscience Methods, Co
      Editor-in-Chief, 2000-2012.

PMID- 25578295
TI  - Evaluation of lung recruitment maneuvers in acute respiratory distress syndrome
      using computer simulation.
AB  - INTRODUCTION: Direct comparison of the relative efficacy of different recruitment
      maneuvers (RMs) for patients with acute respiratory distress syndrome (ARDS) via
      clinical trials is difficult, due to the heterogeneity of patient populations and
      disease states, as well as a variety of practical issues. There is also
      significant uncertainty regarding the minimum values of positive end-expiratory
      pressure (PEEP) required to ensure maintenance of effective lung recruitment
      using RMs. We used patient-specific computational simulation to analyze how three
      different RMs act to improve physiological responses, and investigate how
      different levels of PEEP contribute to maintaining effective lung recruitment.
      METHODS: We conducted experiments on five 'virtual' ARDS patients using a
      computational simulator that reproduces static and dynamic features of a
      multivariable clinical dataset on the responses of individual ARDS patients to a
      range of ventilator inputs. Three recruitment maneuvers (sustained inflation
      (SI), maximal recruitment strategy (MRS) followed by a titrated PEEP, and
      prolonged recruitment maneuver (PRM)) were implemented and evaluated for a range
      of different pressure settings. RESULTS: All maneuvers demonstrated improvements
      in gas exchange, but the extent and duration of improvement varied significantly,
      as did the observed mechanism of operation. Maintaining adequate post-RM levels
      of PEEP was seen to be crucial in avoiding cliff-edge type re-collapse of
      alveolar units for all maneuvers. For all five patients, the MRS exhibited the
      most prolonged improvement in oxygenation, and we found that a PEEP setting of 35
      cm H2O with a fixed driving pressure of 15 cm H2O (above PEEP) was sufficient to
      achieve 95% recruitment. Subsequently, we found that PEEP titrated to a value of
      16 cm H2O was able to maintain 95% recruitment in all five patients. CONCLUSIONS:
      There appears to be significant scope for reducing the peak levels of PEEP
      originally specified in the MRS and hence to avoid exposing the lung to
      unnecessarily high pressures. More generally, our study highlights the huge
      potential of computer simulation to assist in evaluating the efficacy of
      different recruitment maneuvers, in understanding their modes of operation, in
      optimizing RMs for individual patients, and in supporting clinicians in the
      rational design of improved treatment strategies.

PMID- 25578300
TI  - A unified approach to characterize and conserve adaptive and neutral genetic
      diversity in subdivided populations.
AB  - As extinction of local domestic breeds and of isolated subpopulations of wild
      species continues, and the resources available for conservation programs are
      limited, prioritizing subpopulations for conservation is of high importance to
      halt the erosion of genetic diversity observed in endangered species. Current
      approaches usually only take neutral genetic diversity into account. However,
      adaptation of subpopulations to different environments also contributes to the
      diversity found in the species. This paper introduces two notions of adaptive
      variation. The adaptive diversity in a trait is the excess of variance found in
      genotypic values relative to the variance that would have been expected in the
      absence of selection. The adaptivity coverage of a set of subpopulations
      quantifies how well the subpopulations could adapt to a large range of
      environments within a limited time span. Additionally, genome-based notions of
      neutral diversities were obtained that correspond to well known pedigree-based
      definitions. The values of subpopulations for conservation of adaptivity coverage
      were compared with their conservation values for adaptive diversity and neutral
      diversities using simulated data. Conservation values for adaptive diversity and
      neutral diversities were only slightly correlated, but the values for
      conservation of adaptivity coverage showed a reasonable correlation with both
      kinds if the time span was chosen appropriately. Hence, maintaining adaptivity
      coverage is a promising approach to prioritize subpopulations for conservation
      decisions.

PMID- 25578301
TI  - A space-time model for carbapenemase-producing Klebsiella pneumoniae (KPC)
      cluster quantification in a high-complexity hospital.
AB  - A retrospective space-time permutation model with non-Euclidean distance criteria
      was applied within a high-complexity hospital setting to quantitatively explore
      cluster patterns of 273 patients infected with or colonized by carbapenemase
      producing Klebsiella pneumoniae during 4 years. Results were compared to standard
      nosocomial active-surveillance methods. Two clusters were identified in the
      period, suggesting that space-time strategies for cluster quantification within
      confined environments may be useful. 

PMID- 25578302
TI  - [Methotrexate-associated photosensitization].
AB  - BACKGROUND: Methotrexate (MTX), alongside fumaric acid esters, is the most
      commonly used drug in the systemic therapy of psoriasis in Germany. It is
      sometimes used in combination with topical therapy and/or phototherapy due to
      synergistic effects. CASE REPORT: Here we describe a case of phototoxic
      dermatitis during treatment with MTX. Other cutaneous side effects of MTX include
      so-called UV recall, radiation recall, and skin tumor formation.

PMID- 25578303
TI  - [Acrokeratosis paraneoplastica Bazex 6 years prior to diagnosis of gastric
      cancer].
AB  - BACKGROUND: Bazex's syndrome is a rare paraneoplasia that is usually associated
      with cancer. DIAGNOSIS: Characteristic for the disease are diffuse, psoriasis
      like, acral erythema, distal hyperkeratosis and onychodystrophy. Differential
      diagnoses comprise psoriasis, eczema and tinea. CASE REPORT: We present the case
      of a 73-year-old man with acral hyperkeratosis, onychodystrophy, and diffuse
      palmar erythema. Gastric carcinoma was diagnosed by gastroscopy. After a
      gastrectomy was performed, regression of the skin lesions that the patient had
      been suffering from for more than 6 years was observed, confirming the diagnosis
      of Bazex's syndrome.

PMID- 25578305
TI  - Characterization of a novel thermophilic phospholipase B from Thermotoga
      lettingae TMO: applicability in enzymatic degumming of vegetable oils.
AB  - A novel phospholipase B (TLPLB) from Thermotoga lettingae TMO has been cloned,
      functionally overexpressed in Escherichia coli and purified to homogeneity. Gas
      chromatography indicated that the enzyme could efficiently hydrolyze both the sn
      1 and sn-2 ester bonds of 1-palmitoyl-2-oleoyl phosphatidylcholine as
      phospholipase B. TLPLB was optimally active at 70  degrees C and pH 5.5,
      respectively. Its thermostability is relatively high with a half-life of 240 min
      at 90  degrees C. TLPLB also displayed remarkable organic solvent tolerance and
      maintained approximately 91-161 % of its initial activity in 20 and 50 % (v/v)
      hydrophobic organic solvents after incubation for 168 h. Furthermore, TLPLB
      exhibited high degumming activity towards rapeseed, soybean, peanut and sunflower
      seed oils, where the phosphorus contents were decreased from 225.2, 189.3, 85.6
      and 70.4 mg/kg to 4.9, 4.7, 3.2 and 2.2 mg/kg within 5 h, respectively. TLPLB
      could therefore be used for the degumming of vegetable oils. 

PMID- 25578304
TI  - Genome-scale modeling for metabolic engineering.
AB  - We focus on the application of constraint-based methodologies and, more
      specifically, flux balance analysis in the field of metabolic engineering, and
      enumerate recent developments and successes of the field. We also review
      computational frameworks that have been developed with the express purpose of
      automatically selecting optimal gene deletions for achieving improved production
      of a chemical of interest. The application of flux balance analysis methods in
      rational metabolic engineering requires a metabolic network reconstruction and a
      corresponding in silico metabolic model for the microorganism in question. For
      this reason, we additionally present a brief overview of automated reconstruction
      techniques. Finally, we emphasize the importance of integrating metabolic
      networks with regulatory information-an area which we expect will become
      increasingly important for metabolic engineering-and present recent developments
      in the field of metabolic and regulatory integration. 

PMID- 25578306
TI  - Expression and one-step purification of the antimicrobial peptide cathelicidin-BF
      using the intein system in Bacillus subtilis.
AB  - The intein expression system has been widely applied in Escherichia coli to
      express various proteins and peptides. However, the removal of endotoxin from the
      recombinant proteins expressed in E. coli is very difficult and therefore
      complicates the purification process. In this study, we constructed an intein
      based expression vector for an antimicrobial peptide (cathelicidin from Bungarus
      fasciatus) and expressed the intein fusion peptide in a Bacillus subtilis
      expression system. The fusion peptide was secreted into the culture medium,
      identified by Western blot and purified by affinity chromatography and intein
      self-cleavage in just one step. Approximately, 0.5 mg peptide was obtained from 1
      litre of culture medium. The purified peptide showed antimicrobial activity. Our
      results indicate that the intein expression system may be a safe and efficient
      method to produce soluble peptides and proteins in B. subtilis. 

PMID- 25578307
TI  - Maximizing the Yield of Small Samples in Prevention Research: A Review of General
      Strategies and Best Practices.
AB  - The goal of this manuscript is to describe strategies for maximizing the yield of
      data from small samples in prevention research. We begin by discussing what
      "small" means as a description of sample size in prevention research. We then
      present a series of practical strategies for getting the most out of data when
      sample size is small and constrained. Our focus is the prototypic between-group
      test for intervention effects; however, we touch on the circumstance in which
      intervention effects are qualified by one or more moderators. We conclude by
      highlighting the potential usefulness of graphical methods when sample size is
      too small for inferential statistical methods. 

PMID- 25578308
TI  - Stachyose-induced apoptosis of Caco-2 cells via the caspase-dependent
      mitochondrial pathway.
AB  - Some studies have shown that stachyose, as prebiotics, can prevent indirectly
      colon cancer cell growth by promoting the proliferation of probiotics or
      producing beneficial materials in the intestine. However, its direct inhibitory
      effects on cancer cells are still unclear. Thus, this study aims to investigate
      the direct inhibitory effect of stachyose on human colon cancer cells and
      determine the molecular mechanism underlying this effect. The MTT assay was used
      to assess the inhibitory effect of stachyose on Caco-2 cells. Apoptosis and
      mitochondrial membrane potential (DeltaPsim) measurements were analyzed using
      flow cytometry. The activities and mRNA expressions of caspases 3 and 9 were
      determined using caspase assay kits and quantitative real-time polymerase chain
      reaction. The apoptotic protein expressions of Bcl-2, Bax, and cytochrome C (Cyt
      C) were detected through western blotting. Results showed that stachyose inhibits
      Caco-2 cell proliferation and induces apoptosis in a dose-dependent manner. After
      pretreatment with 0.4, 0.8, 1.6 and 3.2 mg mL(-1) stachyose, cell inhibitory
      rates of 15.31% +/- 3.20%, 28.45% +/- 2.10%, 40.23% +/- 5.70%, and 55.67% +/-
      4.50% were respectively obtained. Compared with the control, decreases in
      DeltaPsim, increases in caspase 3 and 9 activities and mRNA expressions, down
      regulation of Bcl-2 protein expression, up-regulation of the Bax protein and Cyt
      C release of Caco-2 cells were clearly observed upon exposure to different
      stachyose concentrations. The inhibitory mechanism of stachyose on Caco-2 cells
      involves the caspase-dependent mitochondrial apoptosis pathway. 

PMID- 25578309
TI  - Facile preparation of ordered mesoporous MnCo2O4 for low-temperature selective
      catalytic reduction of NO with NH3.
AB  - Ordered mesoporous MnCo2O4 nanomaterials were successfully prepared through the
      nanocasting route using SBA-15 and KIT-6 as hard templates. These mesoporous
      nanomaterials were characterized using XRD, BET, TEM, NH3-TPD, H2-TPR, NO-TPD,
      XPS and DRIFT. The low temperature selective catalytic reduction (SCR) activity
      of NO with NH3 was investigated, which revealed that 3D-MnCo2O4 using KIT-6 as a
      template can totally clean all NO over a wide temperature range of 100-250 
      degrees C with a gas hourly space velocity (GHSV) of 32,000 h(-1), while 2D
      MnCo2O4 with SBA-15 as a template had 95% conversion rate at the same condition.
      3D-MnCo2O4 showed the best performance to clean NO due to its typical three
      dimensional porous structure, large specific surface area, abundant active
      surface oxygen species and Lewis acid sites. All the results indicate that a
      novel, cheap catalyst for catalytic removal of NO can be designed by controlling
      the morphology at the nanoscale.

PMID- 25578310
TI  - Gold nanoparticle-loaded filter paper: a recyclable dip-catalyst for real-time
      reaction monitoring by surface enhanced Raman scattering.
AB  - We report a robust and recyclable 'dip-catalyst' based on a gold nanoparticle (Au
      NP)-loaded filter paper composite, prepared by a simple dip-coating process using
      concentrated Au NP suspensions in toluene. While acting as catalysts, the
      composites display excellent surface enhanced Raman scattering (SERS) efficiency,
      allowing the real-time monitoring of chemical reactions. 

PMID- 25578311
TI  - Chronic hepatitis B: role of anti-platelet therapy in inflammation control.
AB  - Platelets play a known role in the maintenance of vascular homeostasis, but these
      cells are emerging as important cellular mediators of acute and chronic
      inflammatory diseases. Platelets are key elements in the pathogenesis of acute
      and chronic liver disease associated with hepatitis B virus (HBV) infection by
      promoting the accumulation of virus-specific CD8(+) T cells and nonspecific
      inflammatory cells into the liver parenchyma. This review discusses major
      platelet functions in immune and inflammatory responses, with an emphasis on
      recent pre-clinical studies that suggest that the inhibition of platelet
      activation pathways represent an alternative therapeutic strategy with potential
      use in the reduction of virus-specific T cell-mediated chronic inflammation,
      liver fibrosis and hepatocellular carcinoma in patients who are chronically
      infected with HBV.

PMID- 25578312
TI  - CMV immunology.

PMID- 25578323
TI  - Stochastic methods for aerosol chemistry: a compact molecular description of
      functionalization and fragmentation in the heterogeneous oxidation of squalane
      aerosol by OH radicals.
AB  - The heterogeneous oxidation of organic aerosol by hydroxyl radicals (OH) can
      proceed through two general pathways: functionalization, in which oxygen
      functional groups are added to the carbon skeleton, and fragmentation, in which
      carbon-carbon bonds are broken, producing higher volatility, lower molecular
      weight products. An ongoing challenge is to develop a quantitative molecular
      description of these pathways that connects the oxidative evolution of the
      average aerosol properties (e.g. size and hygroscopicity) to the transformation
      of free radical intermediates. In order to investigate the underlying molecular
      mechanism of aerosol oxidation, a relatively compact kinetics model is developed
      for the heterogeneous oxidation of squalane particles by OH using free radical
      intermediates that convert reactive hydrogen sites into oxygen functional groups.
      Stochastic simulation techniques are used to compare calculated system properties
      over ten oxidation lifetimes with the same properties measured in experiment. The
      time-dependent average squalane aerosol mass, volume, density, carbon number
      distribution of scission products, and the average elemental composition are
      predicted using known rate coefficients. For functionalization, the calculations
      reveal that the distribution of alcohol and carbonyl groups is controlled
      primarily by the initial OH abstraction rate and to lesser extent by the
      branching ratio between secondary peroxy radical product channels. For
      fragmentation, the calculations reveal that the formation of activated alkoxy
      radicals with neighboring functional groups controls the molecular decomposition,
      particularly at high O/C ratios. This kinetic scheme provides a framework for
      understanding the oxidation chemistry of a model organic aerosol and informs
      parameterizations of more complex systems. 

PMID- 25578313
TI  - The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at
      the maternal-fetal interface in early pregnancy.
AB  - Decidual natural killer (dNK) cells actively participate in the establishment and
      maintenance of maternal-fetal immune tolerance and act as local guardians against
      infection. However, how dNK cells maintain the immune balance between tolerance
      and anti-infection immune responses during pregnancy remains unknown. Here, we
      demonstrated that the inhibitory molecule T-cell immunoglobulin domain and mucin
      domain-containing molecule-3 (Tim-3) are expressed on over 60% of dNK cells. Tim
      3(+) dNK cells display higher interleukin (IL)-4 and lower tumor necrosis factor
      (TNF)-alpha and perforin production. Human trophoblast cells can induce the
      transformation of peripheral NK cells into a dNK-like phenotype via the secretion
      of galectin-9 (Gal-9) and the interaction between Gal-9 and Tim-3. In addition,
      trophoblasts inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokine
      and perforin production by dNK cells, which can be attenuated by Tim-3
      neutralizing antibodies. Interestingly, a decreased percentage of Tim-3
      expressing dNK cells were observed in human miscarriages and murine abortion
      prone models. Moreover, T helper (Th)2-type cytokines were decreased and Th1-type
      cytokines were increased in Tim-3(+) but not Tim-3(-) dNK cells from human and
      mouse miscarriages. Therefore, our results suggest that the Gal-9/Tim-3 signal is
      important for the regulation of dNK cell function, which is beneficial for the
      maintenance of a normal pregnancy. 

PMID- 25578322
TI  - Organic-on-silicon complementary metal-oxide-semiconductor colour image sensors.
AB  - Complementary metal-oxide-semiconductor (CMOS) colour image sensors are
      representative examples of light-detection devices. To achieve extremely high
      resolutions, the pixel sizes of the CMOS image sensors must be reduced to less
      than a micron, which in turn significantly limits the number of photons that can
      be captured by each pixel using silicon (Si)-based technology (i.e., this
      reduction in pixel size results in a loss of sensitivity). Here, we demonstrate a
      novel and efficient method of increasing the sensitivity and resolution of the
      CMOS image sensors by superposing an organic photodiode (OPD) onto a CMOS circuit
      with Si photodiodes, which consequently doubles the light-input surface area of
      each pixel. To realise this concept, we developed organic semiconductor materials
      with absorption properties selective to green light and successfully fabricated
      highly efficient green-light-sensitive OPDs without colour filters. We found that
      such a top light-receiving OPD, which is selective to specific green wavelengths,
      demonstrates great potential when combined with a newly designed Si-based CMOS
      circuit containing only blue and red colour filters. To demonstrate the
      effectiveness of this state-of-the-art hybrid colour image sensor, we acquired a
      real full-colour image using a camera that contained the organic-on-Si hybrid
      CMOS colour image sensor. 

PMID- 25578325
TI  - On-surface formation of two-dimensional polymer via direct C-H activation of
      metal phthalocyanine.
AB  - From high-resolution UHV-STM imaging and DFT calculations we successfully
      obtained a 2D polymer structure formed through direct C-H activation followed by
      an aryl-aryl coupling of a metal-phthalocyanine (CoPc) on Ag(110). 

PMID- 25578324
TI  - The small leucine-rich proteoglycan BGN accumulates in CADASIL and binds to
      NOTCH3.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is an inherited form of cerebral small vessel
      disease caused by mutations in conserved residues of NOTCH3. Affected arteries of
      CADASIL feature fibrosis and accumulation of NOTCH3. A variety of collagen
      subtypes (types I, III, IV, and VI) have been identified in fibrotic CADASIL
      vessels. Biglycan (BGN) and decorin (DCN) are class I members of the small
      leucine-rich proteoglycan (SLRP) family that regulate collagen fibril size.
      Because DCN has been shown to deposit in arteries in cerebral small vessel
      disease, we tested whether BGN accumulates in arteries of CADASIL brains. BGN was
      strongly expressed in both small penetrating and leptomeningeal arteries of
      CADASIL brain. BGN protein was localized to all three layers of arteries (intima,
      media, and adventitia). Substantially, more immunoreactivity was observed in
      CADASIL brains compared to controls. Immunoblotting of brain lysates showed a
      fourfold increase in CADASIL brains (compared to controls). Messenger RNA
      encoding BGN was also increased in CADASIL and was localized by in situ
      hybridization to all three vascular layers in CADASIL. Human cerebrovascular
      smooth muscle cells exposed to purified NOTCH3 ectodomain upregulated BGN, DCN,
      and COL4A1 through mechanisms that are sensitive to rapamycin, a potent mTOR
      inhibitor. In addition, BGN protein interacted directly with NOTCH3 protein in
      cell culture and in direct protein interaction assays. In conclusion, BGN is a
      CADASIL-enriched protein that potentially accumulates in vessels by mTOR-mediated
      transcriptional activation and/or post-translational accumulation via protein
      interactions with NOTCH3 and collagen. 

PMID- 25578326
TI  - Microfluidic-SANS: flow processing of complex fluids.
AB  - Understanding and engineering the flow-response of complex and non-Newtonian
      fluids at a molecular level is a key challenge for their practical utilisation.
      Here we demonstrate the coupling of microfluidics with small angle neutron
      scattering (SANS). Microdevices with high neutron transmission (up to 98%), low
      scattering background (?10-2 cm-1), broad solvent compatibility and high pressure
      tolerance (~3-15 bar) are rapidly prototyped via frontal photo polymerisation.
      Scattering from single microchannels of widths down to 60 MUm, with beam
      footprint of 500 MUm diameter, was successfully obtained in the scattering vector
      range 0.01-0.3 A(-1), corresponding to real space dimensions of ?10-600 A. We
      demonstrate our approach by investigating the molecular re-orientation and
      alignment underpinning the flow response of two model complex fluids, namely
      cetyl trimethylammonium chloride/pentanol/D2O and sodium lauryl
      sulfate/octanol/brine lamellar systems. Finally, we assess the applicability and
      outlook of microfluidic-SANS for high-throughput and flow processing studies,
      with emphasis of soft matter.

PMID- 25578329
TI  - Decitabine: a promising epi-immunotherapeutic agent in solid tumors.
AB  - The incidence of malignancies is increasing worldwide. Despite early detection,
      surgical resection, chemotherapy and radiotherapy, numerous patients continue to
      die from metastasis or recurrence. The immune system has the capacity to
      eradicate cancer cells; however, many tumors, especially solid tumors, present
      considerable challenges that render immune cells ineffectual, making cancer cells
      almost 'invisible' to the immune system. Compelling evidence has demonstrated
      that DNA methylation is involved in tumor development and progression, leading to
      the impaired immunogenicity and immune recognition of cancer cells. The
      hypomethylating agent decitabine has been shown to have therapeutic effects in
      malignancies and exhibits an effective immune efficacy in eliminating cancer
      cells. Based on the hypomethylating and immune remodeling effects of decitabine,
      we propose in this review that decitabine can be considered an epi
      immunotherapeutic agent. We summarize the results of recent preclinical studies
      and clinical trials for decitabine and discuss the connections among its
      hypomethylating effect, immune-activated mechanisms and clinical activity in
      solid tumors, keeping in mind the goal of optimizing dosing schedules. 

PMID- 25578335
TI  - A comparative computational study on the interactions of N719 and N749 dyes with
      iodine in dye-sensitized solar cells.
AB  - The intermolecular interactions of the two most basic Ru(II) complex dyes for dye
      sensitized solar cells (DSSCs), N719 and N749, with the iodine species are
      investigated using density functional theory (DFT). In addition to interactions
      with a single I2 molecule, multiple I2 interactions and simultaneous interactions
      of I2 and I(-) occur. N719 with two isothiocyanato (NCS) ligands interacts with
      two I2 molecules via the two terminal S atoms in the ground singlet electronic
      state, whereas N749 with three NCS ligands forms three S...I-I bonds.
      Irrespective of the NCS position and the number of I2 molecules, N749 has a
      stronger interaction with I2 than N719. Conversely, the interaction of I(-) with
      oxidized N749 via the terminal S atom of the NCS ligand is weaker than that with
      oxidized N719. However, simultaneous interactions of oxidized N749 with two I2
      molecules promote the I(-) interaction, and the I(-) interaction with N749
      becomes stronger than that with N719 bonded to both an I2 and I(-). The
      computational results of multiple interactions between the dye and iodine species
      suggest that the difference in DSSC performance between N719 and N749 dyes is
      explained by recombination related to the I2 interaction and regeneration of the
      oxidized dye by I(-).

PMID- 25578331
TI  - Rituximab-induced remission in a woman with coexisting rheumatoid arthritis and
      nephrotic syndrome.
AB  - We describe a patient with rheumatoid arthritis who presented with nephrotic
      syndrome which was not related neither to drug therapy nor to amyloidosis. Renal
      biopsy revealed membranous glomerulonephritis. The patient was treated with three
      cycles of rituximab with complete resolution of the clinical and laboratory
      evidence of nephrosis. The following report discusses this unusual presentation
      and clinical response. 

PMID- 25578330
TI  - The Prospective Non-Interventional DACCORD Study in the National COPD Registry in
      Germany: design and methods.
AB  - BACKGROUND: A variety of large randomized controlled trials (RCT's) evaluating
      pharmacotherapy in chronic obstructive pulmonary disease (COPD) patients does
      exist. One of the drugs that has been tested is the new long-acting
      anticholinergic glycopyrronium bromide. METHODS: As the generalizability of
      results from RCT's is questionable we designed a longitudinal, prospective non
      interventional study (DACCORD) of two years duration plus two years extension
      with at least 6000 participants in approximately 500 primary and secondary care
      practices in Germany (within the new established COPD National Prospective
      Registry), to assess patient reported outcomes (PRO's), lung function, adherence
      and drug safety. To circumvent the hurdle of inappropriate COPD diagnosis in a
      non-interventional trial, patients have to fulfill the inclusion criteria of the
      COPD disease management program (DMP) of the German statutory health insurances.
      Patient management should follow the German national COPD guidelines, which are
      based on Global Initiative for Chronic Obstructive Lung Disease 2007 (GOLD)
      report. Labels of prescribed drugs should also be taken into account. Patients
      received treatment as part of their standard care: at the discretion of the
      investigator patients were included in one of two arms. A: standard care with
      glycopyrronium containing regimen, and arm B: standard care without
      glycopyrronium. DISCUSSION: For 2016 we expect important results regarding
      longitudinal development of PRO's including exacerbations, lung function,
      adherence and side effects. We also investigate applicability of the new GOLD
      staging system in usual care. Data on diagnostic and treatment modalities in
      current German primary and secondary care, as well as pharmaco-economic data will
      be generated. TRIAL REGISTRATION: 1. German Register for non-interventional
      studies: http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu
      arzneimitteln/nisdb . 2. EMA EnCePP http://www.encepp.eu/ .

PMID- 25578336
TI  - Blood metal concentrations of manganese, lead, and cadmium in relation to serum
      ferritin levels in Ohio residents.
AB  - The objectives of this study were to assess ferritin-specific profiles of blood
      metal concentrations such as manganese, lead, and cadmium and to evaluate whether
      ferritin may affect the behavior of the blood metals in relation to menstruation,
      menopause, or sex in Ohio residents. Recruited participants included residents
      from Marietta, East Liverpool, and Mt. Vernon, OH, USA, who were aged 30-75 years
      and lived at least 10 years in their respective town. The levels of the
      neurotoxic metals such as manganese, cadmium, and lead were assayed in whole
      blood. Serum was analyzed for ferritin level [as a biomarker of iron (Fe)
      status]. An association between blood metal concentrations and independent
      variables (age, serum ferritin, manganese exposure status, and sex) by multiple
      regression analysis was assessed, controlling for various covariates such as BMI,
      educational level, smoking, and alcohol drinking status. Overall, the geometric
      means of blood manganese, cadmium, and lead levels of all participants (n = 276)
      were 9.307 MUg/L, 0.393 MUg/L, and 1.276 MUg/dL, respectively. Log serum ferritin
      concentrations were inversely associated with log blood manganese concentration
      (beta = -0.061 log ferritin and beta = 0.146 categorical ferritin) and log blood
      cadmium concentrations (beta = -0.090 log ferritin and beta = 0.256 categorical
      ferritin). Log serum ferritin concentrations were not associated with log blood
      lead concentrations. Variables of age, sex, and exposure status were not
      associated with log manganese concentrations; however, log blood cadmium
      concentrations were higher in older population, women, and smokers. Log blood
      lead concentrations were higher in older population, men, and postmenopausal
      women. Our study showed that iron deficiency is associated with increased levels
      of blood manganese and cadmium, but not blood lead, in Ohio residents. These
      metals showed different toxicokinetics in relation to age, sex, and menopausal
      status despite similar relationships between ferritin and metal concentrations.

PMID- 25578337
TI  - Fear of Negative Evaluation Influences Eye Gaze in Adolescents with Autism
      Spectrum Disorder: A Pilot Study.
AB  - Social anxiety is common among adolescents with Autism Spectrum Disorder (ASD).
      In this modest-sized pilot study, we examined the relationship between social
      worries and gaze patterns to static social stimuli in adolescents with ASD (n =
      15) and gender-matched adolescents without ASD (control; n = 18). Among
      cognitively unimpaired adolescents with ASD, self-reported fear of negative
      evaluation predicted greater gaze duration to social threat cues (i.e., faces
      depicting disgust and anger). By comparison, there was no relationship between
      self-reported social fears and gaze duration in the controls. These findings call
      attention to the potential import of the impact of co-occurring psychopathology
      such as social anxiety, and particularly fear of negative evaluation, on social
      attention and cognition with adolescents who have ASD.

PMID- 25578338
TI  - Evidence-Based Practices for Children, Youth, and Young Adults with Autism
      Spectrum Disorder: A Comprehensive Review.
AB  - The purpose of this study was to identify evidenced-based, focused intervention
      practices for children and youth with autism spectrum disorder. This study was an
      extension and elaboration of a previous evidence-based practice review reported
      by Odom et al. (Prev Sch Fail 54:275-282, 2010b, doi: 10.1080/10459881003785506
      ). In the current study, a computer search initially yielded 29,105 articles, and
      the subsequent screening and evaluation process found 456 studies to meet
      inclusion and methodological criteria. From this set of research studies, the
      authors found 27 focused intervention practices that met the criteria for
      evidence-based practice (EBP). Six new EBPs were identified in this review, and
      one EBP from the previous review was removed. The authors discuss implications
      for current practices and future research. 

PMID- 25578345
TI  - Burr hole is not burr hole: technical considerations to the evacuation of chronic
      subdural hematomas.
AB  - BACKGROUND: The organization of a multicenter survey about chronic subdural
      hematomas has triggered the discussion on different surgical techniques of burr
      hole evacuation. Such a standard operation gives neurosurgeons plenty of scope
      for creating their own way. METHODS: The procedure presented is one burr hole
      with a closed drainage system. In detail, each single step is enrolled: the
      planning of the burr hole, positioning, direction of skin incision, opening of
      the dura, drain positioning, channeling through the galea, and postoperative
      care. CONCLUSIONS: We present a thorough summary that could serve as a common
      standard and as a basis for comparison of future trials.

PMID- 25578347
TI  - In situ production of therapeutic monoclonal antibodies.
AB  - The use of antibodies as a treatment for disease has it origins in experiments
      performed in the 1890s, and since these initial experiments, monoclonal
      antibodies (mAbs) have become one of the fastest growing therapeutic classes for
      the treatment of cancer, autoimmune disease, and infectious diseases. However,
      treatment with therapeutic mAbs often requires high doses given via long
      infusions or multiple injections, which, coupled with the prohibitively high cost
      associated with the production of clinical-grade proteins and the transient serum
      half-lives that necessitate multiple administrations to gain therapeutic
      benefits, makes large-scale treatment of patients, especially patients in the
      developing world, difficult. Due to their low-cost and rapid scalability, nucleic
      acid-based approaches to deliver antibody gene sequences for in situ mAb
      production have gained substantial traction. In this review, we discuss new
      approaches to produce therapeutic mAbs in situ to overcome the need for the
      passive infusion of purified protein. 

PMID- 25578351
TI  - A Prospective Randomized Trial Comparing Pneumatic Lithotripsy and Holmium Laser
      for Management of Middle and Distal Ureteral Calculi.
AB  - PURPOSE: The aim of this study was to compare the efficacy and safety between
      pneumatic and holmium:yttrium-aluminum-garnet (Ho:YAG) laser in the treatment of
      patients with ureteral stones located in the middle and distal ureter. PATIENTS
      AND METHODS: We conducted a prospective study in recruiting 982 eligible patients
      from 2009 to 2012. Patients were randomly divided into two groups-the pneumatic
      lithotripsy (PL) group or the Ho:YAG laser lithotripsy (LL) group. Patient
      demographics, stone characteristics, intraoperative parameters, and postoperative
      complications were evaluated and analyzed. RESULTS: The baseline demographics of
      patients and stone characteristics were similar in the two groups. The LL group
      showed significant benefits compared with the PL group in terms of mean operative
      time (28+/-9.2 vs 41+/-12.4 min, P=0.001) and early stone-free rate (80.8% vs
      91.3%, P=0.04), but there was no statistically significant difference at the
      third month (92.6% vs 95.5%, P=0.15). In the LL group, 24 postoperative cases of
      stricture were seen, whereas only 5 cases occurred in the PL group (P=0.02). The
      other complications, such as perforation, bleeding, and mucosal injury, were
      comparable in the two groups. The average postoperative stay was also similar
      (1.7+/-2.4 days for PL and 1.5+/-3.1 days for LL (P=0.62). CONCLUSION: Both PL
      and LL are effective in the management of middle and distal impacted stones.
      Ho:YAG laser has advantages in better efficacy of stone fragmentation and a
      higher early stone-free rate but seems to have to face the increased risks of
      postoperative stricture.

PMID- 25578352
TI  - Diabetic nephropathy and proximal tubular damage.
AB  - Diabetic nephropathy (DN) is a major cause of uremia in developed societies.
      Inflammation is emerging as an important mechanism for its pathogenesis and
      progression. Herein, we review 4 recently described cellular receptors that have
      been shown to mediate diabetic interstitial kidney disease. Peroxisome
      proliferator-activated receptor-gamma attenuates STAT-1 activation and has shown
      promise in renoprotection. Its clinical utility is limited mainly by fluid
      retention through upregulation of sodium-hydrogen exchanger-3 and aquaporin-1
      channels in the proximal tubule. The bradykinin receptor 2 of the kallikrein
      kinin system has been shown to mediate diabetic kidney injury and its blockade
      conferred renoprotective effects in animal models of DN. The related protease
      activated receptor, especially receptor 4, has recently been shown to participate
      in DN. Further studies are required to confirm its role. Finally, the toll-like
      receptor, especially TLR4 and TLR2, has been verified in multiple models to be a
      significant sensor of and reactor to hyperglycemia and other diabetic substrates
      that orchestrate interstitial inflammation in DN. 

PMID- 25578353
TI  - Analysis of different thermal processing methods of foodstuffs to optimize
      protein, calcium, and phosphorus content for dialysis patients.
AB  - OBJECTIVE: To analyze how different thermal processing methods affect the
      protein, calcium, and phosphorus content of hospital food served to dialysis
      patients and to generate recommendations for preparing menus that optimize
      nutritional content while minimizing the risk of hyperphosphatemia. DESIGN AND
      METHODS: Standard Official Methods of Analysis (AOAC) methods were used to
      determine dry matter, protein, calcium, and phosphorus content in potatoes, fresh
      and frozen carrots, frozen green beans, chicken, beef and pork, frozen hake,
      pasta, and rice. These levels were determined both before and after boiling in
      water, steaming, stewing in oil or water, or roasting. RESULTS: Most of the
      thermal processing methods did not significantly reduce protein content. Boiling
      increased calcium content in all foodstuffs because of calcium absorption from
      the hard water. In contrast, stewing in oil containing a small amount of water
      decreased the calcium content of vegetables by 8% to 35% and of chicken meat by
      12% to 40% on a dry weight basis. Some types of thermal processing significantly
      reduced the phosphorus content of the various foodstuffs, with levels decreasing
      by 27% to 43% for fresh and frozen vegetables, 10% to 49% for meat, 7% for pasta,
      and 22.8% for rice on a dry weight basis. On the basis of these results, we
      modified the thermal processing methods used to prepare a standard hospital menu
      for dialysis patients. Foodstuffs prepared according to the optimized menu were
      similar in protein content, higher in calcium, and significantly lower in
      phosphorus than foodstuffs prepared according to the standard menu. CONCLUSIONS:
      Boiling in water and stewing in oil containing some water significantly reduced
      phosphorus content without affecting protein content. Soaking meat in cold water
      for 1 h before thermal processing reduced phosphorus content even more. These
      results may help optimize the design of menus for dialysis patients.

PMID- 25578354
TI  - Representation of Ion-Protein Interactions Using the Drude Polarizable Force
      Field.
AB  - Small metal ions play critical roles in numerous biological processes. Of
      particular interest is how metalloenzymes are allosterically regulated by the
      binding of specific ions. Understanding how ion binding affects these biological
      processes requires atomic models that accurately treat the microscopic
      interactions with the protein ligands. Theoretical approaches at different levels
      of sophistication can contribute to a deeper understanding of these systems,
      although computational models must strike a balance between accuracy and
      efficiency in order to enable long molecular dynamics simulations. In this study,
      we present a systematic effort to optimize the parameters of a polarizable force
      field based on classical Drude oscillators to accurately represent the
      interactions between ions (K(+), Na(+), Ca(2+), and Cl(-)) and coordinating amino
      acid residues for a set of 30 biologically important proteins. By combining ab
      initio calculations and experimental thermodynamic data, we derive a polarizable
      force field that is consistent with a wide range of properties, including the
      geometries and interaction energies of gas-phase ion/protein-like model compound
      clusters, and the experimental solvation free-energies of the cations in liquids.
      The resulting models display significant improvements relative to the fixed
      atomic-charge additive CHARMM C36 force field, particularly in their ability to
      reproduce the many-body electrostatic nonadditivity effects estimated from ab
      initio calculations. The analysis clarifies the fundamental limitations of the
      pairwise additivity assumption inherent in classical fixed-charge force fields,
      and shows its dramatic failures in the case of Ca(2+) binding sites. These
      optimized polarizable models, amenable to computationally efficient large-scale
      MD simulations, set a firm foundation and offer a powerful avenue to study the
      roles of the ions in soluble and membrane transport proteins. 

PMID- 25578357
TI  - Corrigendum: laparoscopic distal gastrectomy for gastric cancer in morbidly obese
      patients in South Korea.
AB  - [This corrects the article on p. 187 in vol. 14, PMID: 25328764.]. 

PMID- 25578362
TI  - Microbiota controls the homeostasis of glial cells in the gut lamina propria.
AB  - The intrinsic neural networks of the gastrointestinal tract are derived from
      dedicated neural crest progenitors that colonize the gut during embryogenesis and
      give rise to enteric neurons and glia. Here, we study how an essential
      subpopulation of enteric glial cells (EGCs) residing within the intestinal mucosa
      is integrated into the dynamic microenvironment of the alimentary tract. We find
      that under normal conditions colonization of the lamina propria by glial cells
      commences during early postnatal stages but reaches steady-state levels after
      weaning. By employing genetic lineage tracing, we provide evidence that in adult
      mice the network of mucosal EGCs is continuously renewed by incoming glial cells
      originating in the plexi of the gut wall. Finally, we demonstrate that both the
      initial colonization and homeostasis of glial cells in the intestinal mucosa are
      regulated by the indigenous gut microbiota. 

PMID- 25578365
TI  - Efficacy of controlled-release capsules containing monensin for the prevention of
      subclinical ketosis in pasture-fed dairy cows.
AB  - AIMS: To determine the effectiveness of intra-rumenal controlled release capsules
      (CRC) containing 32 g of monensin administered pre-calving to reduce the
      cumulative incidence of subclinical ketosis (SCK) in mainly pasture-fed dairy
      cows. METHODS: Cows (n=837) due to calve in the first 6 weeks of the spring
      calving period were enrolled from four commercial herds in the Waikato region of
      New Zealand in a blinded, randomised, negative-controlled field trial. Three
      weeks before the start of the calving period cows were randomly allocated to
      receive either no treatment (control) or a single CRC containing monensin and
      then blood sampled on two occasions, 7 days apart within 12 days following
      calving for measurement of concentrations of beta hydroxybutyrate (BHBA) in
      blood. Cows were diagnosed with SCK if the concentration of BHBA in blood in
      either of these samples was >=1.2 mmol/L. RESULTS: Fewer treated cows were
      diagnosed with SCK within 12 days post-calving than control cows (144/340 (42.4%)
      vs. 192/336 (57.1%); p<0.001). There was no interaction between treatment group
      and age, breed or herd of origin. From the final multivariable model it was
      estimated that treatment with CRC containing monensin reduced the absolute
      cumulative incidence of SCK by 17.9 (95% CI=9.2-25.8)% compared to no treatment.
      CONCLUSIONS: Treatment with a CRC containing monensin>10 days prior to calving
      reduced the cumulative incidence of SCK of pasture-based dairy cows in commercial
      dairy herds within 12 days post-calving. CLINICAL RELEVANCE: Administration pre
      calving of an intra-rumenal bolus containing monensin can be considered as one of
      a range of management options for the control of SCK in early lactation.

PMID- 25578366
TI  - The Salience Network and Its Functional Architecture in a Perceptual Decision: An
      Effective Connectivity Study.
AB  - The anterior insulae (INSs) are involved in accumulating sensory evidence in
      perceptual decision-making independent of the motor response, whereas the dorsal
      anterior cingulate cortex (dACC) is known to play a role in choosing appropriate
      behavioral responses. Recent evidence suggests that INSs and dACC are part of the
      salience network (SN), a key network known to be involved in decision-making and
      thought to be important for the coordination of behavioral responses. However,
      how these nodes in the SN contribute to the decision-making process from
      segregation of stimuli to the generation of an appropriate behavioral response
      remains unknown. In this study, the authors scanned 33 participants in functional
      magnetic resonance imaging and asked them to decide whether the presented pairs
      of audio (a beep of sound) and visual (a flash of light) stimuli were synchronous
      or asynchronous. Participants reported their perception with a button press.
      Stimuli were presented in block of eight pairs with a temporal lag (DeltaT)
      between the first (audio) and the second (visual) stimulus in each pair. They
      used dynamic causal modeling (DCM) and the Bayesian model evidence technique to
      elucidate the functional architecture between the nodes of SN. Both the synchrony
      and the asynchrony perception resulted in strong activation in the SN. Most
      importantly, the DCM analyses demonstrated that the INSs were integrating as well
      as driving hubs in the SN. The INSs were found to a play an important role in the
      integration of sensory information; input to the SN is most likely through INSs.
      Furthermore, significant INSs to dACC intrinsic connectivity established by these
      task conditions help us conclude that INSs drive the dACC to guide the behavior
      of choosing the appropriate response. The authors therefore argue that the dACC
      and INS are part of a system involved in the decision-making process from
      perception to planning of a motor response, and that this observed functional
      mechanism might be important during the performance of cognitively demanding goal
      directed tasks. 

PMID- 25578364
TI  - Heterosynaptic regulation of external globus pallidus inputs to the subthalamic
      nucleus by the motor cortex.
AB  - The two principal movement-suppressing pathways of the basal ganglia, the so
      called hyperdirect and indirect pathways, interact within the subthalamic nucleus
      (STN). An appropriate level and pattern of hyperdirect pathway cortical
      excitation and indirect pathway external globus pallidus (GPe) inhibition of the
      STN are critical for normal movement and are greatly perturbed in Parkinson's
      disease. Here we demonstrate that motor cortical inputs to the STN
      heterosynaptically regulate, through activation of postsynaptic NMDA receptors,
      the number of functional GABAA receptor-mediated GPe-STN inputs. Therefore, a
      homeostatic mechanism, intrinsic to the STN, balances cortical excitation by
      adjusting the strength of GPe inhibition. However, following the loss of
      dopamine, excessive cortical activation of STN NMDA receptors triggers GPe-STN
      inputs to strengthen abnormally, contributing to the emergence of pathological,
      correlated activity.

PMID- 25578363
TI  - Cholinergic afferent stimulation induces axonal function plasticity in adult
      hippocampal granule cells.
AB  - Acetylcholine critically influences hippocampal-dependent learning. Cholinergic
      fibers innervate hippocampal neuron axons, dendrites, and somata. The effects of
      acetylcholine on axonal information processing, though, remain unknown. By
      stimulating cholinergic fibers and making electrophysiological recordings from
      hippocampal dentate gyrus granule cells, we show that synaptically released
      acetylcholine preferentially lowered the action potential threshold, enhancing
      intrinsic excitability and synaptic potential-spike coupling. These effects
      persisted for at least 30 min after the stimulation paradigm and were due to
      muscarinic receptor activation. This caused sustained elevation of axonal
      intracellular Ca(2+) via T-type Ca(2+) channels, as indicated by two-photon
      imaging. The enhanced Ca(2+) levels inhibited an axonal KV7/M current, decreasing
      the spike threshold. In support, immunohistochemistry revealed muscarinic M1
      receptor, CaV3.2, and KV7.2/7.3 subunit localization in granule cell axons. Since
      alterations in axonal signaling affect neuronal firing patterns and
      neurotransmitter release, this is an unreported cellular mechanism by which
      acetylcholine might, at least partly, enhance cognitive processing.

PMID- 25578367
TI  - Paclitaxel-loaded micelles enhance transvascular permeability and retention of
      nanomedicines in tumors.
AB  - Paclitaxel (PTX)-loaded polymeric micelles (M-PTX) have been shown to enhance the
      blood flow and oxygenation of tumors 24h after treatment. We hypothesized that
      these changes in the tumor microenvironment could lead to an enhancement of the
      EPR (enhanced permeability and retention) effect. M-PTX, administered 24h before
      analysis, increased the accumulation of macromolecules, nanoparticles and
      polymeric micelles in tumors. This increased EPR effect could be linked to
      normalization of the tumor vasculature and decreased interstitial fluid pressure.
      M-PTX used as a pre-treatment allowed a more effective delivery of three
      nanomedicines into tumors: polymeric micelles, liposomes and nanoparticles. These
      experiments demonstrate an enhanced EPR effect after M-PTX treatment, which lead
      to better availability and enhanced efficacy of a subsequent treatment with
      nanomedicines. 

PMID- 25578368
TI  - Molecular insights into shellac film coats from different aqueous shellac salt
      solutions and effect on disintegration of enteric-coated soft gelatin capsules.
AB  - The purpose of this investigation was to study the effect of using different
      salts of shellac on the disintegration properties of shellac-based enteric
      coatings. In the last two decades, shellac has been increasingly used as an
      aqueous solution for enteric coating purposes, with the ammonium salt being the
      form typically used. Little investigation has been performed on using other
      salts, and therefore, this was the focus of our work. Enteric coatings, based on
      different shellac salts (ammonium, sodium, potassium and composite ammonium
      sodium), were applied onto soft gelatin capsules. Disintegration testing of the
      coated soft gelatin capsules showed that alkali metal salts promote faster
      disintegration than ammonium salts. In order to determine the causes behind these
      differences, the solubility, thermal and spectroscopic properties of films cast
      from the different salts were investigated. The results show that films cast from
      ammonium-based salts of shellac are, unlike those cast from alkali metal-based
      salts, water-insoluble. Spectroscopic evidence suggests that this might be due to
      partial salt dissociation resulting in loss of ammonium as ammonia and reduced
      degree of shellac ionization during drying. In addition, oxidation of shellac
      aldehyde groups of the ammonium-based shellac salts could also play a role. And
      possible higher extent of shellac hydrolysis during the preparation of alkali
      metal salts might also be a factor. Therefore, the nature of the shellac salt
      used in the preparation of shellac-based aqueous coating solutions is a
      significant formulation factor affecting product performance. 

PMID- 25578369
TI  - Lipid-hydrogel films for sustained drug release.
AB  - We report a hybrid system, fabricated from nanostructured lipid particles and
      polysaccharide based hydrogel, for sustained release applications. Lipid
      particles were prepared by kinetically stabilizing self-assembled lipid
      nanostructures whereas the hydrogel was obtained by dissolving kappa-carrageenan
      (KC) in water. The drug was incorporated in native as well as lipid particles
      loaded hydrogels, which upon dehydration formed thin films. The kinetics of drug
      release from these films was monitored by UV-vis spectroscopy while the films
      were characterized by Fourier transform infra-red (FTIR) spectroscopy and small
      angle X-ray scattering techniques. Pre-encapsulation of a drug into lipid
      particles is demonstrably advantageous in certain ways; for instance, direct
      interactions between KC and drug molecules are prohibited due to the mediation of
      hydrophobic forces generated by lipid tails. Rapid diffusion of small drug
      molecules from porous hydrogel network is interrupted by their encapsulation into
      rather large sized lipid particles. The drug release from the lipid-hydrogel
      matrix was sustained by an order of magnitude timescale with respect to the
      release from native hydrogel films. These studies form a strong platform for the
      development of combined carrier systems for controlled therapeutic applications. 

PMID- 25578370
TI  - Critical attributes of formulation and of elaboration process of PLGA-protein
      microparticles.
AB  - Low drug loading, burst effect during release and drug inactivation account for
      the main drawbacks of protein microencapsulation in poly(d,l-lactic-co-glycolic)
      acid (PLGA) matrix by the water-in oil-in water (W/O/W) solvent evaporation
      method. Thus, the current study was set to invest the critical attributes of
      formulation and of elaboration process which determine protein loading into
      microparticles as well as its further release, using albumin as protein model.
      NaCl concentration in the external aqueous phase, poly(vinyl alcohol) (PVA)
      concentration and mostly viscosity of both the internal aqueous phase and the
      organic phase were critical attributes for improving drug loading, with polymer
      molecular weight and hydrophobicity likewise directly related to albumin loading.
      In such a way, when using 0.5% PVA as internal aqueous phase the highest albumin
      loading was achieved. Optimized microparticles exhibited a sustained in vitro
      release of albumin over 130 days. The influence of the microencapsulation process
      on albumin stability and biological activity was evaluated by carrying out cell
      proliferation assays on PC12 cells with albumin released from microparticles.
      Such assay demonstrated that the microencapsulation procedure optimized in this
      study did not affect the biological stability of the microencapsulated protein. 

PMID- 25578371
TI  - Primary reciprocity-based method for calibration of hydrophone magnitude and
      phase sensitivity: complete tests at frequencies from 1 to 7 MHz.
AB  - A primary reciprocity-based method for calibration of hydrophone magnitude and
      phase sensitivity is proposed. The method starts determining the transmit
      transfer function of an auxiliary transducer, based on the self-reciprocity
      method and using a stainless steel cylinder as reflecting target. Afterwards, the
      hydrophone, to be calibrated, is positioned facing the auxiliary transducer. The
      pressure field waveform, calculated at the hydrophone spot and based on the
      transmit transfer function of an auxiliary transducer, is used together with the
      output end of cable voltage waveform signal from the hydrophone to yield the
      calibrated hydrophone sensitivity. The method was tested with two similar
      membrane hydrophones, at frequencies within the 1.0-7.0 MHz range, in steps of
      1.0 MHz. Results for magnitude sensitivity agree, within a confidence level of
      95%, with those from previous calibration of same hydrophones at the National
      Physical Laboratory, in the UK (Enor?1.0). Phase sensitivity results agree with
      literature reported ones concerning the achieved uncertainty. Additionally, the
      phase sensitivities measured at 5.0 MHz for two similar hydrophones and employing
      two distinct auxiliary transducers presented no statistical significant
      difference. The method yielded a relative expanded uncertainty (p=0.95) for the
      sensitivity magnitude ranging between 6.6 and 7.0%, and an expanded uncertainty
      (p=0.95) ranging between 12 degrees  and 17 degrees  for the phase sensitivity.
      The results obtained so far lead to conclude that the proposed hydrophone
      calibration method is a validated alternative to the different existing methods.

PMID- 25578372
TI  - Changes of explicitly and implicitly measured self-esteem in the treatment of
      major depression: evidence for implicit self-esteem compensation.
AB  - BACKGROUND AND OBJECTIVES: Self-esteem has been claimed to be an important factor
      in the development and maintenance of depression. Whereas explicit self-esteem is
      usually reduced in depressed individuals, studies on implicitly measured self
      esteem in depression exhibit a more heterogeneous pattern of results, and the
      role of implicit self-esteem in depression is still ambiguous. Previous research
      on implicit self-esteem compensation (ISEC) revealed that implicit self-esteem
      can mirror processes of self-esteem compensation under conditions that threaten
      self-esteem. We assume that depressed individuals experience a permanent threat
      to their selves resulting in enduring processes of ISEC. We hypothesize that ISEC
      as measured by implicit self-esteem will decrease when individuals recover from
      depression. METHODS: 45 patients with major depression received an integrative in
      patient treatment in the Psychosomatic University Hospital Bonn, Germany.
      Depression was measured by the depression score of the Hospital Anxiety and
      Depression Scale (HADS-D). Self-esteem was assessed explicitly using the
      Rosenberg Self-Esteem Scale (RSES) and implicitly by the Implicit Association
      Test (IAT) and the Name Letter Test (NLT). RESULTS: As expected for a successful
      treatment of depression, depression scores declined during the eight weeks of
      treatment and explicit self-esteem rose. In line with our hypothesis, both
      measures of implicit self-esteem decreased, indicating reduced processes of ISEC.
      LIMITATIONS: It still remains unclear, under which conditions there is an overlap
      of measures of implicit and explicit self-esteem. CONCLUSIONS: The results lend
      support to the concept of ISEC and demonstrate the relevance of implicit self
      esteem and self-esteem compensation for the understanding of depression.

PMID- 25578373
TI  - Direct NMR detection of bifurcated hydrogen bonding in the alpha-helix N-caps of
      ankyrin repeat proteins.
AB  - In biomolecules, bifurcated H-bonds typically involve the interaction of two
      donor protons with the two lone pairs of oxygen. Here, we present direct NMR
      evidence for a bifurcated H-bonding arrangement involving nitrogen as the
      acceptor atom. Specifically, the H-bond network comprises the Ndelta1 atom of
      histidine and both the backbone N-H and side-chain Ogamma-H of threonine within
      the conserved TXXH motif of ankyrin repeat (AR) proteins. Identification of the H
      bonding partners is achieved via solution NMR H-bond scalar coupling (HBC) and
      H/D isotope shift experiments. Quantitative determination of (2h)J(NN) HBCs
      supports that Thr N-H...Ndelta1 His H-bonds within internal repeats are stronger
      (~4 Hz) than in the solvent exposed C-terminal AR (~2 Hz). In agreement, pKa
      values for the buried histidines bridging internal ARs are several units lower
      than those of the C-terminus. Quantum chemical calculations show that the
      relevant (2h)J and (1h)J couplings are dominated by the Fermi contact
      interaction. Finally, a Thr-to-Val replacement, which eliminates the Thr Ogamma
      H...Ndelta1 His H-bond and decreases protein stability, results in a 25% increase
      in (2h)J(NN), attributed to optimization of the Val N-H...Ndelta1 His H-bond.
      Overall, the results provide new insights into the H-bonding properties of
      histidine, a refined structural rationalization for the folding cooperativity of
      AR proteins, and a challenging benchmark for the calculation of HBCs.

PMID- 25578377
TI  - Tumour size is the only predictive factor of distant recurrence after
      pathological complete response to neoadjuvant chemotherapy in patients with large
      operable or locally advanced breast cancers: a sub-study of EORTC 10994/BIG 1-00
      phase III trial.
AB  - PURPOSE: Although achieving a pathological complete response (pCR) after
      neoadjuvant chemotherapy (NACT) in breast cancer predicts a better outcome, some
      patients still relapse. The objectives of this study were to describe the types
      of events in this group of patients and to identify predictive factors for
      relapse. METHODS: Patients with large operable or locally advanced breast cancers
      (T4d tumours were excluded) were randomised to receive either six cycles of
      anthracycline-based chemotherapy or three cycles of docetaxel followed by three
      cycles of eprirubicin/docetaxel. pCR was defined as no evidence of residual
      invasive cancer (or very few scattered tumour cells) in the primary tumour and
      axillary lymph nodes at surgery. Two Cox regression analyses were performed to
      identify predictive factors of relapse: one for recurrence-free interval (RFI)
      and one for distant recurrence-free interval (DRFI). RESULTS: Out of 283 eligible
      patients who achieved a pCR, 40 (14.1%) and 28 (9.9%) presented an event of
      interest for the RFI and DRFI analyses, respectively. Five-year RFI, DRFI and
      overall survival (OS) were 85.3% (95% confidence interval (CI), 80.1-89.3), 89.6%
      (95% CI, 85.0-92.9) and 91.9% (95% CI, 87.2-94.9), respectively. No predictors
      for RFI after pCR were identified. For DRFI, tumour size was the only predictor:
      Hazard ratio (HR) T3 versus T1-2=3.62 (95% CI, 1.66-7.89); HR T4 versus T1-2: HR,
      2.80 (95% CI, 0.62-12.64) p=0.0048. CONCLUSION: In this study, clinical tumour
      size emerged as the only predictor for DRFI after pCR, with T3 and T4 tumours
      having an increased risk for distant recurrence compared to T1-2 tumours.

PMID- 25578378
TI  - Developing sporophytes transition from an inducible to a constitutive ecological
      strategy of desiccation tolerance in the moss Aloina ambigua: effects of
      desiccation on fitness.
AB  - BACKGROUND AND AIMS: Two ecological strategies of desiccation tolerance exist in
      plants, constitutive and inducible. Because of difficulties in culturing
      sporophytes, very little is known about desiccation tolerance in this generation
      and how desiccation affects sexual fitness. METHODS: Cultured sporophytes and
      vegetative shoots from a single genotype of the moss Aloina ambigua raised in the
      laboratory were tested for their strategy of desiccation tolerance by desiccating
      the shoot-sporophyte complex and vegetative shoots at different intensities, and
      comparing outcomes with those of undried shoot-sporophyte complexes and
      vegetative shoots. By using a dehardened clonal line, the effects of field, age
      and genetic variance among plants were removed. KEY RESULTS: The gametophyte and
      embryonic sporophyte were found to employ a predominantly inducible strategy of
      desiccation tolerance, while the post-embryonic sporophyte was found to employ a
      moderately constitutive strategy of desiccation tolerance. Further, desiccation
      reduced sporophyte fitness, as measured by sporophyte mass, seta length and
      capsule size. However, the effects of desiccation on sporophyte fitness were
      reduced if the stress occurred during embryonic development as opposed to
      postembryonic desiccation. CONCLUSIONS: The effects of desiccation on dehardened
      sporophytes of a bryophyte are shown for the first time. The transition from one
      desiccation tolerance strategy to the other in a single structure or generation
      is shown for only the second time in plants and for the first time in bryophytes.
      Finding degrees of inducible strategies of desiccation tolerance in different
      life phases prompts the formulation of a continuum hypothesis of ecological
      desiccation tolerance in mosses, where desiccation tolerance is not an either/or
      phenomenon, but varies in degree along a gradient of ecological inducibility.

PMID- 25578380
TI  - An intervention aimed at reducing plagiarism in undergraduate nursing students.
AB  - Plagiarism is a current and developing problem in the tertiary education sector
      where students access information and reproduce it as their own. It is identified
      as occurring in many tertiary level degrees including nursing and allied health
      profession degrees. Nursing specifically, is a profession where standards and
      ethics are required and honesty is paramount. The aim of this study was to
      evaluate the change in nursing student's knowledge and understanding of
      plagiarism before and after an educational intervention in their first semester
      of the Bachelor of nursing degree at a private college of higher education in
      Sydney, Australia. This study concluded that an educational intervention can
      increase knowledge and awareness of plagiarism among nursing students. 

PMID- 25578379
TI  - Phylogenetic relationships in Epidendroideae (Orchidaceae), one of the great
      flowering plant radiations: progressive specialization and diversification.
AB  - BACKGROUND AND AIMS: The largest subfamily of orchids, Epidendroideae, represents
      one of the most significant diversifications among flowering plants in terms of
      pollination strategy, vegetative adaptation and number of species. Although many
      groups in the subfamily have been resolved, significant relationships in the tree
      remain unclear, limiting conclusions about diversification and creating
      uncertainty in the classification. This study brings together DNA sequences from
      nuclear, plastid and mitochrondrial genomes in order to clarify relationships, to
      test associations of key characters with diversification and to improve the
      classification. METHODS: Sequences from seven loci were concatenated in a
      supermatrix analysis for 312 genera representing most of epidendroid diversity.
      Maximum-likelihood and parsimony analyses were performed on this matrix and on
      subsets of the data to generate trees and to investigate the effect of missing
      values. Statistical character-associated diversification analyses were performed.
      KEY RESULTS: Likelihood and parsimony analyses yielded highly resolved trees that
      are in strong agreement and show significant support for many key clades. Many
      previously proposed relationships among tribes and subtribes are supported, and
      some new relationships are revealed. Analyses of subsets of the data suggest that
      the relatively high number of missing data for the full analysis is not
      problematic. Diversification analyses show that epiphytism is most strongly
      associated with diversification among epidendroids, followed by expansion into
      the New World and anther characters that are involved with pollinator
      specificity, namely early anther inflexion, cellular pollinium stalks and the
      superposed pollinium arrangement. CONCLUSIONS: All tested characters show
      significant association with speciation in Epidendroideae, suggesting that no
      single character accounts for the success of this group. Rather, it appears that
      a succession of key features appeared that have contributed to diversification,
      sometimes in parallel.

PMID- 25578381
TI  - Preparing for disasters: education and management strategies explored.
AB  - During the last half of the 20th century, the focus of nursing changed from home
      and field to high-tech clinics and hospitals. Nursing in the absence of
      technology due to man-made or natural disasters almost disappeared from the
      curriculum of many nursing schools. Numerous disaster events and threats in the
      early 21st century caused educators and practitioners to increase the emphasis on
      disaster nursing and those principles that guide the nurse's practice in response
      to disasters. This article chronicles tools used by nurse educators to integrate
      disaster nursing into the didactic and clinical experiences of baccalaureate
      nursing students. We represent two nursing schools about 90 miles apart that
      collaborated to provide students with practical application of disaster nursing
      concepts. Part 1: An educational journey toward disaster nursing competencies: A
      curriculum in action provides an overview of the curricular tools used to insure
      adequate coverage of disaster nursing concepts across the curriculum. Part 2:
      Collaborative learning in Community Health Nursing for emergency preparedness
      relates the steps taken to plan, implement, and evaluate two different
      collaborative disaster simulation events. In this manuscript we have attempted
      transparency so that others can learn from our successes and our failures. 

PMID- 25578382
TI  - eSimulation: A novel approach to enhancing cultural competence within a health
      care organisation.
AB  - The need for Australian health care organisations to deliver culturally competent
      and safe care to its increasingly diverse population provided the impetus for the
      development of an interactive eSimulation module "Communicating with Patients
      from Culturally and Linguistically Diverse Backgrounds, Case Study: Ms Shu Fen
      Chen". This article discusses the rationale, development and implementation of
      the module. Feedback from sixty nurses and allied health professionals indicated
      the module was highly engaging and had a positive impact on learners' confidence,
      knowledge and clinical practice. It is concluded that eSimulation modules can
      contribute to the uptake of cultural competency training and create a foundation
      for further initiatives to enhance the provision of culturally competent health
      care. 

PMID- 25578383
TI  - General population reference values for 3-level EQ-5D (EQ-5D-3L) questionnaire in
      Poland.
AB  - INTRODUCTION: A Polish EQ-5D normative study published in 2010 was conducted in
      2008 as a pilot study. The group of respondents was relatively small and had
      limited representativeness. OBJECTIVES: The aim of the study was to derive
      population norms for the 3-level EQ-5D (EQ-5D-3L) questionnaire in Poland using a
      large, representative sample. RESPONDENTS AND METHODS: Stratified random sampling
      was used. A total of 3941 respondents (age, 18-87 years) completed the self
      administered paper-based EQ-5D-3L questionnaire (3973 completed the visual analog
      scale, EQ VAS) and were included in this study. Utility index scores were derived
      using the Polish time trade-off value set. RESULTS: The study sample was
      representative of the general Polish population in terms of age, sex,
      geographical region, type and size of a given locality, level of education, and
      social and professional status. Mean EQ-5D-3L and visual analogue scale (EQ VAS)
      values decreased from 0.968 and 86.2 (age group, 18-24 years) to 0.730 and 54.0
      (age group, >=75 years), respectively. The most frequently reported complaints
      were pain/discomfort (45.8%) followed by anxiety/depression (33.3%), while the
      least commonly reported problem was self-care (9.4%). CONCLUSIONS: Polish
      population norms developed for the EQ-5D-3L index, descriptive part of the EQ-5D
      3L, and EQ VAS can be used as reference values. The availability of such
      normative data should encourage the use of EQ-5D-3L in health-related quality-of
      life studies in Poland.  

PMID- 25578384
TI  - The effects of panaxadiol saponins on megakaryocytic maturation and immune
      function in a mouse model of immune thrombocytopenia.
AB  - We have identified a biologically active component, panaxadiol saponins component
      (PDS-C), from Chinese ginseng herb extract. Panaxadiol saponins component
      contains five ginsenoside monomers with total purity of 92.44%. In this study,
      the BALB/c mouse model with immune thrombocytopenia (ITP) was established by
      injection of antiplatelet antibody every other day for 5 total times; the
      peripheral blood platelet counts steadily decreased to 20%-30% of normal levels
      and remained decreased for about 10 days. The antiplatelet antibody was derived
      from the sera of guinea pigs immunized with the platelets of BALB/c mice. Mice
      with ITP were treated with PDS-C at a low, a moderate, or a high dose for 10
      consecutive days. We observed that the peripheral blood platelet counts of ITP
      mice were significantly higher than that of ITP controls (untreated) after
      treatment of PDS-C in a dose-dependent manner. Treatment with PDS-C also
      increased the mature megakaryocytes in the bone marrow of treated ITP animals
      with a concomitant decease of immature megakaryocyte precursors. Furthermore,
      macrophage phagocytosis of exogenous erythrocytes in the intra-abdominal cavity
      of ITP mice was inhibited by PDS-C treatment, indicating that PDS-C also could
      modulate immune function and may possibly prevent phagocytosis of antibody-coated
      platelets. Altogether, our findings suggest that PDS-C may have a dual role,
      promoting proliferation and differentiation of megakaryocytes, as well as
      modulating immune function, and it may therefore be very helpful in the treatment
      of ITP. 

PMID- 25578386
TI  - Extension and flexion in the upper cervical spine in neck pain patients.
AB  - Neck pain is a common problem in the general population with high risk of ongoing
      complaints or relapses. Range of motion (ROM) assessment is scientifically
      established in the clinical process of diagnosis, prognosis and outcome
      evaluation in neck pain. Anatomically, the cervical spine (CS) has been
      considered in two regions, the upper and lower CS. Disorders like cervicogenic
      headache have been clinically associated with dysfunctions of the upper CS (UCS),
      yet ROM tests and measurements are typically conducted on the whole CS. A cross
      sectional study assessing 19 subjects with non-specific neck pain was undertaken
      to examine UCS extension-flexion ROM in relation to self-reported disability and
      pain (via the Neck Disability Index (NDI)). Two measurement devices (goniometer
      and electromagnetic tracking) were employed and compared. Correlations between
      ROM and the NDI were stronger for the UCS compared to the CS, with the strongest
      correlation between UCS flexion and the NDI-headache (r = -0.62). Correlations
      between UCS and CS ROM were fair to moderate, with the strongest correlation
      between UCS flexion and CS extension ROM (r = -0.49). UCS flexion restriction is
      related to headache frequency and intensity. Consistency and agreement between
      both measurement systems and for all tests was high. The results demonstrate that
      separate UCS ROM assessments for extension and flexion are useful in patients
      with neck pain.

PMID- 25578385
TI  - Atg5 but not Atg7 in dendritic cells enhances IL-2 and IFN-gamma production by
      Toxoplasma gondii-reactive CD4+ T cells.
AB  - The autophagy proteins (Atg) modulate not only innate but also adaptive immunity
      against pathogens. We examined the role of dendritic cell Atg5 and Atg7 in the
      production of IL-2 and IFN-gamma by Toxoplasma gondii-reactive CD4(+) T cells. T.
      gondii-reactive mouse CD4(+) T cells exhibited unimpaired production of IL-2 and
      IFN-gamma when stimulated with Atg7-deficient mouse dendritic cells that were
      infected with T. gondii or pulsed with T. gondii lysate antigens. In marked
      contrast, dendritic cells deficient in Atg5 induced diminished CD4(+) T cell
      production of IL-2 and IFN-gamma. This defect was not accompanied by changes in
      costimulatory ligand expression on dendritic cells or impaired production of IL
      12 p70, IL-1beta or TNF-alpha. Knockdown of Irg6a in dendritic cells did not
      affect CD4(+) T cell cytokine production. These results indicate that Atg5 and
      Atg7 in dendritic cells play differential roles in the modulation of IL-2 and IFN
      gamma production by T. gondii-reactive CD4(+) T cells. 

PMID- 25578387
TI  - Clinical pharmacology of analgesic drugs in cattle.
AB  - Providing pain relief in cattle is challenging. In the absence of labeled drugs,
      the Animal Medicinal Drug Use Clarification Act regulates the extralabel drug use
      of analgesics in cattle within the United States. Given the variety of
      pharmacokinetic and pharmacodynamic properties of pain-relieving drugs, evidence
      needs to drive the development of analgesic protocols for cattle during pain
      related events. This article reviews the commonly used analgesics investigated in
      cattle including local anesthetics, nonsteroidal anti-inflammatory drugs,
      opioids, alpha2-agonists, N-methyl-d-aspartate receptor antagonists, and
      gabapentin. These compounds are examined with respect to evidence of analgesia in
      cattle during pain states. 

PMID- 25578388
TI  - Evidence for the use of ceftiofur for treatment of metritis in dairy cattle.
AB  - Metritis is a cause of postparturient uterine disease in dairy cattle and is most
      commonly associated with watery fetid red-brown uterine discharge occurring in
      the first 21 days postpartum. The most severe form of metritis (puerperal
      metritis) often warrants antibiotic therapy. This article analyzes the current
      literature to determine the efficacy of ceftiofur in the treatment of metritis.
      Evidence-based review of the current literature suggests that there is evidence
      for the use of ceftiofur in the treatment of metritis. However, review of the
      literature also reveals the need for more studies with negative control groups.

PMID- 25578389
TI  - A review of the expected effects of antimicrobials in bovine respiratory disease
      treatment and control using outcomes from published randomized clinical trials
      with negative controls.
AB  - Bovine respiratory disease (BRD) remains a major disease from an economic and an
      animal welfare standpoint in beef production systems. Antimicrobial
      administration is a mainstay in the control of and therapeutic treatment of acute
      BRD. Judicious use of antimicrobials remains paramount to ensure efficacy of
      treatment remains acceptable. A systemic review was conducted in the scientific
      literature, the objective of which was to present a cumulative review of the data
      from published randomized clinical trials using a negative control in the
      treatment and control of BRD and using the number needed to treat as a means to
      effectively convey this information to bovine practitioners. 

PMID- 25578390
TI  - Adsorption in alumina pores open at one and at both ends.
AB  - We have studied adsorption in regular, self-ordered alumina pores open at both
      ends or only at one end. The straight, non-connected pores have diameters ranging
      from 22 to 83 nm, with a relative dispersion below 1% in the pore size.
      Adsorption isotherms measured in open pores with a torsional microbalance show
      pronounced hysteresis loops characterized by nearly vertical and parallel
      adsorption and desorption branches. Blocking one end of the pores with glue has a
      strong influence on adsorption, as expected from classical macroscopic arguments.
      However, the experimental measurements show an unexpectedly rich phenomenology
      dependent on the pore size. For large pores (Dp >= 67 nm), the isotherms for
      closed end pores present much narrower hysteresis loops whose adsorption and
      desorption boundaries envelop the desorption branches of the isotherms for the
      corresponding open pores of the same size. The loop for small closed end pores
      (Dp = 22 nm) is slightly wider than that for open pores while the adsorption
      branches coincide. For large pores, in contrast, the desorption branches of pores
      with the same Dp overlap regardless of the pore opening. These observations are
      in agreement with our grand canonical Monte Carlo (GCMC) simulations for a
      cylindrical pore model with constrictions, suggesting that the alumina pores
      could be modeled using a constricted pore model whose adsorption isotherm depends
      on the ratio of the constriction size to the pore size (Dc/Dp). 

PMID- 25578391
TI  - Metal-organic framework materials for light-harvesting and energy transfer.
AB  - A critical review of the emerging field of MOFs for photon collection and
      subsequent energy transfer is presented. Discussed are examples involving MOFs
      for (a) light harvesting, using (i) MOF-quantum dots and molecular chromophores,
      (ii) chromophoric MOFs, and (iii) MOFs with light-harvesting properties, and (b)
      energy transfer, specifically via the (i) Forster energy transfer and (ii) Dexter
      exchange mechanism. 

PMID- 25578392
TI  - Are QTc interval changes after meal intake a reasonable method to prove assay
      sensitivity in thorough QT studies?

PMID- 25578393
TI  - The 25-hydroxyvitamin D3 C-3 epimer: distribution, correlates, and
      reclassification of 25-hydroxyvitamin D status in the population-based
      Atherosclerosis Risk in Communities Study (ARIC).
AB  - BACKGROUND: Little is known about the vitamin D3 epimer [3-epi-25(OH)D3],
      particularly in adults. We describe characteristics of the D3 epimer within the
      community-based ARIC cohort. METHODS: The vitamin D3 epimer, 25(OH)D3, and
      25(OH)D2 were measured using LC-MS/MS in stored serum collected in 1990-1992 from
      9,887 white and 3,221 black ARIC study participants, aged 46-70years. Cross
      sectional characteristics were explored. RESULTS: Concentrations of the epimer
      were quantifiable (>=1.41ng/ml) in 33.4% of whites and 15.0% of blacks and made
      up on average 3.23% and 2.25% of total D3 [epimer+25(OH)D3] concentrations,
      respectively. Epimer levels were positively correlated with 25(OH)D3 in both
      whites (r=0.54) and blacks (r=0.36) and were unrelated to 25(OH)D2
      concentrations. Overall, epimer levels were associated with participant
      characteristics in a manner similar to that typically observed for 25(OH)D3.
      Including the epimer in the calculation of total 25(OH)D resulted in
      approximately 2% of participants being reclassified from being clinically 25(OH)D
      deficient to having suboptimal levels. CONCLUSIONS: Low concentrations of the D3
      epimer were present in adult serum and overall the epimer concentration is
      moderately correlated with the 25(OH)D3 concentration. The reclassification of
      participant's clinical 25(OH)D status upon inclusion of the epimer was minimal.

PMID- 25578395
TI  - Galectin-1 and galectin-3: plausible tumour markers for oral squamous cell
      carcinoma and suitable targets for screening high-risk population.
AB  - BACKGROUND: Galectins are a family of carbohydrate binding proteins that regulate
      several cellular functions such as growth, migration, adhesion and apoptosis.
      METHODS: We investigated the expression of galectin (gal)-1 and galectin (gal)-3
      in patients with oral squamous cell carcinoma (OSCC) and observed their effects
      on growth and survival of OSCC cell lines. RESULTS: OSCC patients expressed
      significantly higher levels of gal-1 and gal-3 in circulation (p<0.0001) and at
      the tumour sites (p<0.01) as compared to controls. Patients with higher tumour
      load showed significantly higher expression of both galectins than those with
      lower tumour load. In ROC analysis, serum levels of gal-1 and gal-3 at cut-off
      values of 4.875 and 0.871ng/ml respectively, discriminated between healthy
      subjects and patients with more than 80% sensitivity and specificity. Similarly,
      logistic regression analysis revealed about 3-times higher risk of OSCC in
      subjects over expressing these proteins. Further, exogenous gal-1 and gal-3
      significantly increased survival, proliferation and angiogenesis in OSCC cell
      lines. CONCLUSIONS: Serum levels of gal-1 and gal-3 may serve as plausible
      markers for oral squamous cell carcinoma and may be useful in screening
      population at a higher risk.

PMID- 25578394
TI  - Exome sequencing and pathway analysis for identification of genetic variability
      relevant for bronchopulmonary dysplasia (BPD) in preterm newborns: A pilot study.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common chronic lung
      disease in infancy, affecting preterm children with low birth weight. The disease
      has a multifactorial aetiology with a significant genetic component; until now
      published association studies have identified several candidate genes but only
      few of these data has been replicated. In this pilot study, we approached exome
      sequencing aimed at identifying non-common variants, which are expected to have a
      stronger phenotypic effect. MATERIALS AND METHODS: We performed this study on 26
      Italian severely affected BPD preterm unrelated newborns, homogeneously selected
      from a large prospective cohort. We used an Illumina HiSeq 2000 for sequencing.
      Data analysis was focussed on genes previously associated to BPD susceptibility
      and to new candidates in related pathways, highlighted by a prioritization
      analysis performed using ToppGene Suite. RESULTS: By exome sequencing, we
      identified 3369 novel variants, with a median of 400 variations per sample. The
      top candidate genes highlighted were NOS2, MMP1, CRP, LBP and the toll-like
      receptor (TLR) family. All of them have been confirmed with Sanger sequencing.
      CONCLUSIONS: Potential candidate genes have been discovered in this preliminary
      study; the pathogenic role of identified variants will need to be confirmed with
      functional and segregation studies and possibly with further methods, able to
      evaluate the collective influence of rare variants. Moreover, additional
      candidates will be tested and genetic analysis will be extended to all affected
      children.

PMID- 25578396
TI  - In vitro and in vivo evaluation of the marine sponge skeleton as a bone mimicking
      biomaterial.
AB  - This investigation was carried out to identify and characterize marine sponges as
      potential bioscaffolds in bone tissue engineering. The marine sponge (Biemna
      fortis) samples were collected from the rocky intertidal region of Anjuna, Goa,
      India, freeze-dried and converted to pure cristobalite at low temperature. After
      thorough evaluation of sponge samples by DTA-TGA thermography, XRD, FTIR, SEM and
      cell cytotoxicity by MTT assay, bare sponge scaffolds were fabricated by firing
      at 1190  degrees C. These scaffolds were loaded with growth factors (IGF-1 and
      BMP-2), checked for quasi-dynamic in vitro release kinetics and finally implanted
      into femoral bone defects in rabbits for up to 90 days, by keeping an empty
      defect as a control. The in vivo bone healing process was evaluated and compared
      using chronological radiology, histology, SEM and fluorochrome labeling studies.
      SEM revealed that the sponge skeleton possesses a collagenous fibrous network
      consisting of highly internetworked porosity in the size range of 10-220 MUm. XRD
      and FTIR analysis showed a cristobalite phase with acicular crystals of high
      aspect ratio, and crystallinity was found to increase from 725 to 1190  degrees
      C. MTT assay demonstrated the non-cytotoxicity of the samples. A combination of
      burst and sustained release profile was noticed for both the growth factors and
      about 74.3% and 83% total release at day 28. In the radiological, histological,
      scanning electron microscopy and fluorochrome labeling analysis, the IGF-1
      impregnated converted sponge scaffold promoted excellent osseous tissue formation
      followed by the BMP-2 loaded and bare one. These observations suggest that the
      marine sponge alone and in combination with growth factors is a promising
      biomaterial for bone repair and bone augmentation. 

PMID- 25578397
TI  - [Rehabilitation in the German statutory accident insurance. Guide to the new
      outpatient and inpatient structures].
AB  - BACKGROUND: The German statutory accident insurance (DGUV) has the statutory
      mandate to eliminate or to prevent an aggravation of the consequences of
      accidents by all appropriate means and is based on the principle of
      rehabilitation before pension. For this, special methods have been developed in
      recent decades, such as employer's mutual insurance inpatient further treatment
      (BGSW, Berufsgenossenschaftliche Stationare Weiterbehandlung) and extended
      outpatient physiotherapy (EAP, Erweiterte Ambulante Physiotherapie). In 2012 the
      workplace-related musculoskeletal rehabilitation (ABMR, Arbeitsplatz-bezogene
      muskuloskelettale Rehabilitation) was added to these complex treatments. SPECIAL
      REHABILITATION MEASURES: For complex injuries and delayed healing these methods
      approach their limits. The accident clinics of the Association of Clinics in
      Statutory Accident Insurance (KUV, Klinikverbund der gesetzlichen
      Unfallversicherung) provide a number of specialized rehabilitation measures in
      order to ensure an optimal seamless rehabilitation of the severely injured. In
      addition to complex inpatient rehabilitation (KSR, Komplexe Stationare
      Rehabilitation) integrated special rehabilitation procedures, such as
      neurorehabilitation for severely traumatic brain injured patients and
      rehabilitation after spinal cord injury and other special rehabilitation methods,
      such as occupation-oriented rehabilitation (TOR, Tatigkeitsorientierte
      Rehabilitation) and pain rehabilitation, ensure that the German Society for
      Trauma Surgery (DGU) phase model of trauma rehabilitation is implemented. This
      provides an early start in the context of acute treatment as so-called early
      rehabilitation. After a specialized post-acute rehabilitation, additional
      therapeutic options are often required. CONCLUSION: An appropriate treatment of
      severely injured patients is important, for example through rehabilitation
      managers, which must not end with discharge from the rehabilitation hospital. The
      aim of all efforts is the reintegration into the working and social environment
      in addition to the best possible quality of life.

PMID- 25578399
TI  - Predictors of institutionalization for people with multiple sclerosis.
AB  - BACKGROUND: Multiple Sclerosis (MS) is a chronic, progressive disease of the
      central nervous system with a high prevalence in Canada. While the disease course
      is highly variable, a significant portion of people with MS may spend more than
      10 years living with severe disability, and many of those will eventually require
      full time institutional care. Despite the high personal and economic cost of this
      care, little is known about predictors of institutionalization. OBJECTIVE: The
      objective of this study was to identify predictors of institutionalization.
      METHODS: Longitudinal data from a university MS clinic database were extracted to
      explore nursing home placement over time of an urban subgroup. Cox regression
      analysis was performed with age of MS onset and sex, as well as baseline
      information obtained at the first MS clinic assessment: MS course, Kurtzke
      Expanded Disability Status Scale score, and functional system scores. RESULTS:
      Older age of onset (p = .019) and higher baseline scores in specific functional
      systems (cerebellar, bowel/bladder, brainstem, and cerebral/mental) were
      significant (p = .000, p = .000, p = .001, p = .000 respectively) predictors of
      nursing home placement. CONCLUSIONS: Patients with older age of MS onset and
      those with baseline impairment in specific functional systems (cerebellar,
      bowel/bladder, brainstem, and cerebral/mental) may be at higher risk for future
      institutionalization and should be assessed with particular care to determine
      potential avenues of support to minimize this.

PMID- 25578400
TI  - Large Autosomal Copy-Number Differences within Unselected Monozygotic Twin Pairs
      are Rare.
AB  - Monozygotic (MZ) twins form an important system for the study of biological
      plasticity in humans. While MZ twins are generally considered to be genetically
      identical, a number of studies have emerged that have demonstrated copy-number
      differences within a twin pair, particularly in those discordant for disease. The
      rate of autosomal copy-number variation (CNV) discordance within MZ twin pairs
      was investigated using a population sample of 376 twin pairs genotyped on
      Illumina Human610-Quad arrays. After CNV calling using both QuantiSNP and PennCNV
      followed by manual annotation, only a single CNV difference was observed within
      the MZ twin pairs, being a 130 KB duplication of chromosome 5. Five other
      potential discordant CNV were called by the software, but excluded based on
      manual annotation of the regions. It is concluded that large CNV discordance is
      rare within MZ twin pairs, indicating that any CNV difference found within
      phenotypically discordant MZ twin pairs has a high probability of containing the
      causal gene(s) involved. 

PMID- 25578398
TI  - The APC tumor suppressor is required for epithelial cell polarization and three
      dimensional morphogenesis.
AB  - The Adenomatous Polyposis Coli (APC) tumor suppressor has been previously
      implicated in the control of apical-basal polarity; yet, the consequence of APC
      loss-of-function in epithelial polarization and morphogenesis has not been
      characterized. To test the hypothesis that APC is required for the establishment
      of normal epithelial polarity and morphogenesis programs, we generated APC
      knockdown epithelial cell lines. APC depletion resulted in loss of polarity and
      multi-layering on permeable supports, and enlarged, filled spheroids with
      disrupted polarity in 3D culture. Importantly, these effects of APC knockdown
      were independent of Wnt/beta-catenin signaling, but were rescued with either full
      length or a carboxy (c)-terminal segment of APC. Moreover, we identified a gene
      expression signature associated with APC knockdown that points to several
      candidates known to regulate cell-cell and cell-matrix communication. Analysis of
      epithelial tissues from mice and humans carrying heterozygous APC mutations
      further supports the importance of APC as a regulator of epithelial behavior and
      tissue architecture. These data also suggest that the initiation of epithelial
      derived tumors as a result of APC mutation or gene silencing may be driven by
      loss of polarity and dysmorphogenesis. 

PMID- 25578402
TI  - Impact of copy number variations burden on coding genome in humans using
      integrated high resolution arrays.
AB  - Copy number variations (CNVs) alter the transcriptional and translational levels
      of genes by disrupting the coding structure and this burden of CNVs seems to be a
      significant contributor to phenotypic variations. Therefore it was necessary to
      assess the complexities of CNV burden on the coding genome. A total of 1715
      individuals from 12 populations were used for CNV analysis in the present
      investigation. Analysis was performed using Affymetrix Genome-Wide Human SNP
      Array 6.0 chip and CytoScan High-Density arrays. CNVs were more frequently
      observed in the coding region than in the non-coding region. CNVs were observed
      vastly more frequently in the coding region than the non-coding region. CNVs were
      found to be enriched in the regions containing functional genes (83-96%) compared
      with the regions containing pseudogenes (4-17%). CNVs across the genome of an
      individual showed multiple hits across many genes, whose proteins interact
      physically and function under the same pathway. We identified varying numbers of
      proteins and degrees of interactions within protein complexes of single
      individual genomes. This study represents the first draft of a population
      specific CNV genes map as well as a cross-populational map. The complex
      relationship of CNVs on genes and their physically interacting partners unravels
      many complexities involved in phenotype expression. This study identifies four
      mechanisms contributing to the complexities caused by the presence of multiple
      CNVs across many genes in the coding part of the genome.

PMID- 25578401
TI  - HMGB1 modulates Lewis cell autophagy and promotes cell survival via RAGE-HMGB1
      Erk1/2 positive feedback during nutrient depletion.
AB  - Autophagy is a self-digesting mechanism responsible for the removal of long-lived
      proteins and damaged organelles by lysosomes. It also allows cells to survive
      during nutrient depletion and/or in the absence of growth factors. High-mobility
      group protein 1 (HMGB1) is a highly-conserved nuclear protein that has been
      associated with cell autophagy; however, the mechanisms responsible for this role
      remain unclear. Many reports have demonstrated that autophagy represents a
      survival strategy for tumor cells during nutrient depletion, oxidative stress and
      DNA damage. In the present study, we explored the mechanisms whereby HMGB1
      regulates tumor cell autophagy during nutrient depletion (the cells were cultured
      in Hank's balanced salt solution, HBSS). HMGB1 expression in Lewis cells
      increased and the protein was shuttled from the nucleus to the cytoplasm and was
      secreted, coincident with up-regulation of autophagy. Prevention of HMGB1 binding
      to the receptor for advanced glycation end products (RAGE) or knock-down of HMGB1
      expression led to inhibition of autophagy and increased apoptosis. These results
      demonstrated a positive feedback pathway whereby starvation of Lewis cells
      promoted HMGB1 secretion, allowing cells to survive by regulating autophagy via a
      RAGE-HMGB1-extracellular signal-regulated kinase1/2-dependent pathway. These
      results also implicate HMGB1 as a potential risk factor for cancer growth and
      metastasis. 

PMID- 25578403
TI  - A monoclonal antibody against glycoproteins of Aspergillus fumigatus shows anti
      adhesive potential.
AB  - There has been an increase in the cases of fungal resistance against many
      antifungal drugs and an effective alternative mode in the form of immunotherapy
      is being considered as new hope. The adhesion of Aspergillus fumigatus conidia to
      the host components is one of the prime factors to cause aspergillosis.
      Carbohydrate components or glycoproteins present on the cell surface play an
      important role in interaction of the organism to the host and leads to adhesion.
      Any substance which is capable of disrupting this interaction may be a vital tool
      for the fungal clearance and hence may protect the host from infections caused by
      the fungus. In this study, a murine monoclonal antibody IgM generated against the
      secretory antigens of A. fumigatus, was found to be specific to a common epitope
      containing glyco-moieties of the various proteins and exhibited anti-adhesive
      potential in vitro.

PMID- 25578404
TI  - The correlation of the "Walking Estimated-Limitation Calculated by History"
      (WELCH) questionnaire with treadmill maximal walking time is not impaired by age,
      in patients with claudication.
AB  - PURPOSE: The "Walking Estimated-Limitation Calculated by History" (WELCH)
      questionnaire is a short four-item questionnaire that estimates the walking
      capacity of a patient in comparison with relatives, friends or people the same
      age. As such, it should be relatively insensitive to age, yet this has never been
      tested. METHODS: A prospective study was performed among 525 patients presenting
      vascular-type claudication. Patients were grouped into quintiles of age-from
      quintile 1 for the youngest patients to quintile 5 for the oldest ones. Patients
      completed a self-administered questionnaire and then had their maximal walking
      time (MWT) measured on a treadmill. We estimated the coefficient of correlation,
      the slope and the intercept of the relationship between the WELCH score and the
      MWT, then the accuracy of a WELCH score under 25 to predict the ability to walk
      for 5 min on a treadmill. RESULTS: The slopes of the relationships and the
      correlation coefficients were not significantly different in each quintile, but a
      significant shift in the intercept of regressing lines was found with age.
      Nevertheless, the accuracy in predicting treadmill results from the WELCH score
      with a cut-off point of 25 was, respectively, 68.6, 72.4, 80.0, 72.4 and 73.3 %
      in quintiles 1, 2, 3, 4 and 5 (p = 0.45). CONCLUSIONS: The relationship of MWT on
      a treadmill and the WELCH score is slightly influenced by age, but a score
      superior to 25 seems to be of equal discriminatory performance in different
      quintiles of age to predict the ability to walk for 5 min on a treadmill. This
      makes this cut-off limit of interest for routine use, regardless of age.

PMID- 25578405
TI  - Optimal Control of a Delayed SIRS Epidemic Model with Vaccination and Treatment.
AB  - This article deals with optimal control applied to vaccination and treatment
      strategies for an SIRS epidemic model with logistic growth and delay. The delay
      is incorporated into the model in order to modeled the latent period or
      incubation period. The existence for the optimal control pair is also proved.
      Pontryagin's maximum principle with delay is used to characterize these optimal
      controls. The optimality system is derived and then solved numerically using an
      algorithm based on the forward and backward difference approximation. 

PMID- 25578406
TI  - Environmental effects on fibre reinforced polymeric composites: evolving reasons
      and remarks on interfacial strength and stability.
AB  - The interface between fibre and matrix of fibrous polymeric composites is most
      critical and decisive in maintaining sustainability, durability and also
      reliability of this potential material, but unfortunately a comprehensive
      conclusion is yet to meet the label of confidence for the engineering viability.
      Fiber reinforced polymer (FRP) composites are being accepted and also utilized as
      better and reliable alternative materials for repairing and/or replacing
      conventional materials, starting from tiny objects to mega structure in various
      engineering applications. The promise and potential of these materials are
      sometimes threatened in speedy replacement of conventional materials because of
      their inhomogeneities and inherent susceptibility to degradation due to moist and
      thermal environments. Environmental conditioning is traditionally believed to be
      a physical phenomenon but present literature has revealed that the interdiffusion
      between fiber and polymer matrix resin comprises of physical, chemical,
      mechanical, physico-chemical and mechano-chemical phenomena. The failure and
      fracture behavior at ambient conditions itself is a complex phenomenon till at
      present. The service conditions which are mostly hygrothermal in nature, along
      with a variation of applied loads make the mechanical behavior nearly
      unpredictable, far off from conclusions in evaluating the short term as well as
      long term durability and reliability of FRPs. It is essential to accurately
      simulate the initial and subsequent evolution process of this kind of damage
      phenomena, in order to explore the full potential of the mechanical properties of
      composite laminates. The present review has emphasized the need of complying
      scattered as well as limited literature on this front, and has focused on
      creating the urgency to highlight the importance of judicious uses of these
      materials with minimum safety factors with an aim to achieving lighter weight in
      enhancing specific properties. 

PMID- 25578407
TI  - Aphron applications--a review of recent and current research.
AB  - Colloidal aphrons are multi-layered stable bubbles (CGAs) or droplets (CLAs),
      surrounded by a thin surfactant film. The small size of the aphrons creates a
      system with a high interfacial area which can be pumped like water without
      collapsing. The high stability of colloidal aphrons due to a thin soapy shell
      surrounding the core, and high interfacial area make them of interest in many
      processes such as mineral processing, protein recovery, drilling fluids,
      separation of organic dyes from waste water, predispersed solvent extraction of
      dilute streams, clarification and purification of suspensions, soil remediation,
      material synthesis and immobilization of enzymes. This article aims to provide a
      comprehensive database in generation, characterization and applications of
      colloidal gas and liquid aphrons from more than 140 published works so far. The
      article also reports scale up, industrial applications, technical limitation
      regarding aphrons application and important future research scopes. 

PMID- 25578408
TI  - Sessile nanofluid droplet drying.
AB  - Nanofluid droplet evaporation has gained much audience nowadays due to its wide
      applications in painting, coating, surface patterning, particle deposition, etc.
      This paper reviews the drying progress and deposition formation from the
      evaporative sessile droplets with the suspended insoluble solutes, especially
      nanoparticles. The main content covers the evaporation fundamental, the particle
      self-assembly, and deposition patterns in sessile nanofluid droplet. Both
      experimental and theoretical studies are presented. The effects of the type,
      concentration and size of nanoparticles on the spreading and evaporative dynamics
      are elucidated at first, serving the basis for the understanding of particle
      motion and deposition process which are introduced afterward. Stressing on
      particle assembly and production of desirable residue patterns, we express
      abundant experimental interventions, various types of deposits, and the effects
      on nanoparticle deposition. The review ends with the introduction of theoretical
      investigations, including the Navier-Stokes equations in terms of solutions, the
      Diffusion Limited Aggregation approach, the Kinetic Monte Carlo method, and the
      Dynamical Density Functional Theory. Nanoparticles have shown great influences in
      spreading, evaporation rate, evaporation regime, fluid flow and pattern formation
      of sessile droplets. Under different experimental conditions, various deposition
      patterns can be formed. The existing theoretical approaches are able to predict
      fluid dynamics, particle motion and deposition patterns in the particular cases.
      On the basis of further understanding of the effects of fluid dynamics and
      particle motion, the desirable patterns can be obtained with appropriate
      experimental regulations. 

PMID- 25578409
TI  - Visceral angioedema: an under-recognized complication of angiotensin-converting
      enzyme inhibitors.
AB  - Cough and upper airway angioedema are well-recognized adverse reactions of
      angiotensin-converting enzyme inhibitor (ACEI) therapy. Visceral angioedema is an
      infrequent and often unrecognized complication of ACEI therapy. We describe a
      patient in whom the diagnosis was delayed for > 2 years. A 60-year-old woman with
      hypertension on treatment with enalapril presented with complaints of abdominal
      pain and diarrhea for 2 days. Physical examination was significant for diffuse
      abdominal tenderness and hypotension. Laboratory data were normal except for
      leukocytosis and elevated creatinine. Computed tomography (CT) of the abdomen
      showed diffuse small bowel wall thickening. ACEI-induced visceral angioedema was
      considered, enalapril was discontinued and supportive care was provided.
      Patient's symptoms and CT appearance improved 48 and 72 hours, respectively,
      after stopping enalapril. She remained symptom-free 1 year after discharge.

PMID- 25578410
TI  - Aqueous vanadium ion dynamics relevant to bioinorganic chemistry: A review.
AB  - Aqueous solutions of the four highest vanadium oxidation states exhibit four
      diverse colors, which only hint at the diverse reactions that these ions can
      undergo. Cationic vanadium ions form complexes with ligands; anionic vanadium
      ions form complexes with ligands and self-react to form isopolyanions. All
      vanadium species undergo oxidation-reduction reactions. With a few exceptions,
      elucidation of the dynamics of these reactions awaited the development of fast
      reaction techniques before the kinetics of elementary ligation, condensation,
      reduction, and oxidation of the aqueous vanadium ions could be investigated. As
      the biological roles played by endogenous and therapeutic vanadium expand, it is
      appropriate to bring the results of the diverse kinetics studies under one
      umbrella. To achieve this goal this review presents a systematic examination of
      elementary aqueous vanadium ion dynamics. 

PMID- 25578411
TI  - Ferric microperoxidase-11 catalyzes peroxynitrite isomerization.
AB  - Microperoxidase-11 (MP11) is an undecapeptide derived from horse heart cytochrome
      c offering the possibility to study the reactivity of the heme group relatively
      unshielded by the protein. Here, the peroxynitrite isomerization to NO3(-)
      catalyzed by ferric MP11 (MP11-Fe(III)) is reported. Data were obtained between
      pH3.6 and 8.1, at 20.0 degrees C. The value of the second-order rate constant
      (kon) for peroxynitrite isomerization to NO3(-) by MP11-Fe(III) decreases from
      (1.1+/-0.1)*10(5)M(-1)s(-1), at pH3.6, to (6.1+/-0.6)*10(3)M(-1)s(-1), at pH8.1.
      The pH dependence of kon (pKa=6.9) suggests that peroxynitrous acid reacts
      preferentially with MP11-Fe(III). The MP11-Fe(III)-catalyzed isomerization of
      peroxynitrite to NO3(-) has been ascribed to the reactive penta-coordinated heme
      Fe atom of MP11-Fe(III). In fact, cyanide binding to the sixth coordination
      position of the heme-Fe atom inhibits the MP11-Fe(III)-catalyzed isomerization of
      peroxynitrite to NO3(-). The values of the first-order rate constant (k0) for
      isomerization of peroxynitrite to NO3(-) in the presence of the MP11-Fe(III)-CN
      complex are superimposable to those obtained in the absence of MP-Fe(III). Values
      of kon for peroxynitrite isomerization to NO3(-) by MP11-Fe(III) overlap those
      obtained for penta-coordinated cardiolipin-cytochrome c complex and for
      carboxymethylated cytochrome c in absence and presence of cardiolipin. Present
      results highlight the role of the heme-Fe(III) co-ordination state in the
      modulation of cytochrome c reactivity. 

PMID- 25578412
TI  - On raising the "dust of blood": from unrevealing thrombopoiesis to treatment of
      thrombocytopenias with thrombomimetic drugs.

PMID- 25578413
TI  - Thrombopoiesis.
AB  - The production of platelets is a complex process that involves hematopoietic stem
      cells (HSCs), their differentiated progeny, the marrow microenvironment and
      hematopoietic cytokines. Much has been learned in the 110 years since James Homer
      Wright postulated that marrow megakaryocytes were responsible for blood platelet
      production, at a time when platelets were termed the "dust of the blood". In the
      1980s a number of in vitro culture systems were developed that could produce
      megakaryocytes, followed by the identification of several cytokines that could
      stimulate the process in vitro. However, none of these cytokines produced a
      substantial thrombocytosis when injected into animals or people, nor were blood
      levels inversely related to platelet count, the sine qua non of a physiological
      regulator. A major milestone in our understanding of thrombopoiesis occurred in
      1994 when thrombopoietin, the primary regulator of platelet production was cloned
      and initially characterized. Since that time many of the molecular mechanisms of
      thrombopoiesis have been identified, including the effects of thrombopoietin on
      the survival, proliferation, and differentiation of hematopoietic stem and
      progenitor cells, the development of polyploidy and proplatelet formation, the
      final fragmentation of megakaryocyte cytoplasm to yield blood platelets, and the
      regulation of this process. While much progress has been made, several
      outstanding questions remain, such as the nature of the signals for final
      platelet formation, the molecular nature of the regulation of marrow stromal
      thrombopoietin production, and the role of these physiological processes in
      malignant hematopoiesis. 

PMID- 25578414
TI  - Development of romiplostim: a novel engineered peptibody.
AB  - Thrombopoietin (TPO) is a growth factor that stimulates megakaryocytes to
      increases platelet counts. Due to concerns around the development of
      autoantibodies in clinical studies of TPO, a novel peptide that bound the TPO
      receptor was used to develop a TPO mimetic. This peptide has no shared homology
      with TPO, and therefore avoids the risk of development of antibodies that cross
      react with endogenous TPO. The ability of the artificial peptide to bind and
      stimulate the TPO receptor was improved by dimerization of the peptide, and the
      stability of the peptide was improved by linking the peptides to the Fc portion
      of an antibody. Romiplostim (Nplate, Amgen, Inc, Thousand Oaks, CA) is the first
      fully engineered fusion of a novel peptide and antibody or "peptibody" that can
      stimulate platelet production. 

PMID- 25578415
TI  - Treatment of immune thrombocytopenia in adults: the role of thrombopoietin
      receptor agonists.
AB  - The pathophysiology, classification, epidemiology, and treatment of immune
      thrombocytopenia (ITP) have witnessed great progresses in the last decade and are
      briefly addressed here. After more than 5 years of use in clinical practice, a
      new class of drugs acting as thrombopoietin-receptor (TPO-R) agonists is gaining
      a more definite role in the treatment of primary ITP in adults. The two currently
      available agents (romiplostim and eltrombopag) have similar efficacies and only
      slightly different safety profiles, despite their profound structural differences
      and their different activation mechanisms of the megakaryocyte TPO-R. They are
      effective in restoring a safe platelet count in 70%-80% of cases with chronic ITP
      failing one or more lines of treatment, including splenectomy. A limitation is
      represented by the great fluctuation of platelet counts during treatment and the
      need to continue treatment indefinitely. However, there are limited data
      suggesting that some patients can stop treatment and maintain a safe platelet
      count for quite long periods. Bleeding events are generally also greatly reduced
      during their use but not totally aborted. Safety concerns are not definitely
      clarified with regard to a possible increased risk of arterial and venous
      thrombosis, whereas the risk of inducing marrow fibrosis seems negligible at
      least for treatments shorter than 2-3 years. TPO-R agonists' place as a
      replacement for splenectomy or rituximab remains controversial. Treating patients
      at presentation or during the persistent phase of ITP is an exciting prospect
      that needs comparative randomized studies. 

PMID- 25578416
TI  - Treatment of pediatric primary immune thrombocytopenia with thrombopoietin
      receptor agonists.
AB  - Chronic immune thrombocytopenia (ITP) occurs in approximately one fifth of
      children with primary ITP and is characterized by a significant lack of clinical
      data. A minority of these children exhibit bleeding and need treatment. Often
      standard therapy used for patients with newly diagnosed ITP is administered to
      stop bleeding and to increase the platelet count. These drugs are associated with
      adverse effects, which is particularly evident when used during long time. In
      adult patients with chronic ITP, thrombopoietin receptor agonists (TPO-RAs)
      demonstrated efficacy in approximately 80% of patients. These drugs have been
      studied intensely for registration purposes; however, for children and
      adolescents they are not yet approved and studies are ongoing. First experiences
      with these drugs show similar effects and safety as in adults, though based on
      very small numbers of children. These drugs have the potential to be used during
      long time, in order to increase platelets, to stop or prevent bleeding and to
      augment quality of life, making long-term safety an important issue. 

PMID- 25578418
TI  - Treatment of myelodysplastic syndrome with thrombomimetic drugs.
AB  - Myelodysplastic syndromes (MDS) are clinically, genetically, and molecularly
      heterogeneous neoplastic diseases characterized by ineffective hematopoiesis
      leading to peripheral cytopenias. The severity of cytopenias influences oucome
      and is considered in prognostic scoring systems; thrombocytopenia, although not
      the most frequently observed at disease onset, is estimated to affect 40%-80% of
      MDS patients. As thrombocytopenia in MDS is determined by premature marrow
      destruction and programmed cell death, the use of thrombomimetic agents has been
      proposed in order to stimulate megakaryocyte differentation and proliferation.
      After early attempts of therapy of thrombocytopenic MDS patients with
      thrombopoietin and interleukin (IL)-11, clinical trials testing the activity of
      romiplostim and eltrombopag have been recently designed and have demonstrated
      good tolerability and efficacy in re-inducing megakaryocytopoiesis and in
      lowering the number of hemorragic events. The number of MDS patients receiving
      such treatments is still limited and a broader evaluation of the long-term
      effects and safety of these agents is ongoing. 

PMID- 25578417
TI  - Eltrombopag in aplastic anemia.
AB  - The treatment of aplastic anemia is currently with immunosuppressive therapy
      (IST) with anti-thymocyte globulin (ATG) and cyclosporine, to which two thirds of
      patients respond. However, a significant proportion of these responders relapse
      and many have persistent cytopenias. The management of these patients is
      challenging. Modifications to this standard approach using alternative
      immunosuppressive agents or adding hematopoietic cytokines such as granulocyte
      colony-stimulating factor (G-CSF) and erythropoietin (EPO) have not improved
      outcome. A recent trial has shown that eltrombopag, a thrombopoeitin mimetic, is
      efficacious in the treatment of patients with severe aplastic anemia (SAA)
      refractory to IST. There is evidence that this drug works by directly stimulating
      marrow stem and progenitor cells thereby promoting hematopoietic recovery in
      patients with bone marrow failure. Several trials are ongoing in our institution
      using this very promising drug in combination therapy in the upfront treatment of
      SAA, in IST-refractory SAA and in moderate disease. 

PMID- 25578419
TI  - Thrombopoietin receptor agonists: a critical review.
AB  - Thrombopoietic agents have created a paradigm shift in the management of chronic
      or poorly responsive immune thrombocytopenia (ITP). There are ample randomized,
      placebo-controlled trial data, as well as long-term data gathered for more than 5
      years; short-term efficacy and safety are well documented and long-term efficacy
      and safety data are emerging. The purpose of this review will be to focus
      critically on what we know or do not know at this point about these agents. We
      review the evolution, efficacy and clinical use, side effects, special
      populations, and off-target effects of the thrombopoietic agents. 

PMID- 25578420
TI  - The first case of breast cancer in thalassemic patient: case report and review of
      literature.
AB  - Thalassemias are genetic disorders characterized by decreased synthesis of one of
      the globin chains. Beta-thalassemia is caused by impairment in the production of
      beta-globin chains leaving the excess alpha chains unstable. With better
      treatment approaches and improvement in chelation therapy, thalassemic patients
      are living longer. As a consequence, new complications and associations with
      other conditions including malignancy have emerged. The occurrence of
      malignancies in thalassemia has rarely been reported, and our review of the
      literature revealed only few cases. We report the first case of a thalassemic
      patient developing breast cancer and discuss the possibility of a link between
      the two disease entities. This case is intended to alert physicians of the
      possibility of a malignancy in thalassemia patients. 

PMID- 25578421
TI  - Near infrared laser stimulation of human neural stem cells into neurons on
      graphene nanomesh semiconductors.
AB  - Reduced graphene oxide nanomeshes (rGONMs), as p-type semiconductors with band
      gap energy of ~ 1 eV, were developed and applied in near infrared (NIR) laser
      stimulation of human neural stem cells (hNSCs) into neurons. The biocompatibility
      of the rGONMs in growth of hNSCs was found similar to that of the graphene oxide
      (GO) sheets. Proliferation of the hNSCs on the GONMs was assigned to the excess
      oxygen functional groups formed on edge defects of the GONMs, resulting in
      superhydrophilicity of the surface. Under NIR laser stimulation, the graphene
      layers (especially the rGONMs) exhibited significant cell differentiations,
      including more elongations of the cells and higher differentiation of neurons
      than glia. The higher hNSC differentiation on the rGONM than the reduced GO (rGO)
      was assigned to the stimulation effects of the low-energy photoexcited electrons
      injected from the rGONM semiconductors into the cells, while the high-energy
      photoelectrons of the rGO (as a zero band-gap semiconductor) could suppress the
      cell proliferation and/or even cause cell damages. Using conventional heating of
      the culture media up to ~ 43  degrees C (the temperature typically reached under
      the laser irradiation), no significant differentiation was observed in dark. This
      further confirmed the role of photoelectrons in the hNSC differentiation.

PMID- 25578422
TI  - Mechanical and cell-to-cell adhesive properties of aggregated Methanosarcina.
AB  - The mechanical and adhesive properties as well as the turgor pressure of microbes
      play an important role in cell growth and aggregation. By applying AFM together
      with finite element modelling, one can determine the cell wall structural
      homogeneity, mechanical and cell-to-cell adhesive properties for aggregated
      Methanosarcina barkeri cells. This also allows a novel approach to determine in
      aggregate turgor pressure determination. Analyzing the AFM force-indentation
      response of the aggregates under loads less than 10 nN, our study reveals
      structural inhomogeneity of the polymeric part of the cell wall material and
      suggests that the cell wall consists of two layers of methanochondroitin
      (external: with a thickness of 3 +/- 1 nm and internal: with a thickness of 169
      +/- 30 nm). On average, the hyperelastic finite element model showed that the
      internal layer is more rigid (MU = 14 +/- 4 MPa) than the external layer (MU =
      2.8 +/- 0.9 MPa). To determine the turgor pressure and adhesiveness of the cells,
      a specific mode of indentation (under a load of 45 nN), aimed towards the centre
      of the individual aggregate, was performed. By modelling the AFM induced
      decohesion of the aggregate, the turgor pressure and the cell-to-cell adhesive
      interface properties could be determined. On average, the turgor pressure is
      estimated to be 59 +/- 22 kPa, the interface strength is 78 +/- 12 kPa and the
      polymer network extensibility is 2.8 +/- 0.9 nm. We predict that internal cell
      wall comprised highly compressed methanochondroitin chains and we are able to
      identify a conceptual model for stress dependent inner cell wall growth.

PMID- 25578430
TI  - Functional correlates of preserved naming performance in amnestic Mild Cognitive
      Impairment.
AB  - Naming abilities are typically preserved in amnestic Mild Cognitive Impairment
      (aMCI), a condition associated with increased risk of progression to Alzheimer's
      disease (AD). We compared the functional correlates of covert picture naming and
      word reading between a group of aMCI subjects and matched controls. Unimpaired
      picture naming performance was associated with more extensive activations, in
      particular involving the parietal lobes, in the aMCI group. In addition, in the
      condition associated with higher processing demands (blocks of categorically
      homogeneous items, living items), increased activity was observed in the aMCI
      group, in particular in the left fusiform gyrus. Graph analysis provided further
      evidence of increased modularity and reduced integration for the homogenous sets
      in the aMCI group. The functional modifications associated with preserved
      performance may reflect, in the case of more demanding tasks, compensatory
      mechanisms for the subclinical involvement of semantic processing areas by AD
      pathology. 

PMID- 25578431
TI  - The cellular protective effects of rosmarinic acid: from bench to bedside.
AB  - Rosemary (Rosmarinus officinalis L.) is one of the most common household herbs,
      used as spices in a variety of foods, and employed in traditional medicine for
      its healing properties. Rosemary is a rich source of active antioxidant
      constituents such as phenolic diterpenes, flavonoids and phenolic acids. Caffeic
      acid and rosmarinic acid are the most important bioactive constituents.
      Rosmarinic acid is the ester of caffeic acid and 3,4-dihydroxyphenyllactic acid
      and is widely identified in different plant species. Chemical structure of
      rosmarinic acid contains two phenolic rings: one of them is derived from
      phenylalanine via caffeic acid and the other from tyrosine via dihydroxyphenyl
      lactic acid. Its large-scale production is obtained from plant cell cultures of
      Coleus blumei Benth. It is easily absorbed through gastrointestinal tract as well
      as the skin. Rosmarinic acid is one of the most important and well known natural
      antioxidant compounds, which possesses neuroprotective effects in different
      models of neuroinflammation, neurodegeneration, as well as chemicalinduced
      neurotoxicity and oxidative stress. Therefore, in present review, we aim to
      discuss about chemistry, sources, biotechnological production and neuroprotective
      actions of rosmarinic acid with emphasis on its possible molecular mechanisms of
      neuroprotection. 

PMID- 25578432
TI  - Changes in urine proteome accompanying diabetic nephropathy progression.
AB  - INTRODUCTION: Owing to the prevalence of type 2 diabetes, diabetic kidney disease
      (DKD) becomes the major cause of end-stage renal disease. The current markers of
      diabetic nephropathy are based on albuminuria and clinical signs of retinopathy.
      Sensitive and specific noninvasive diagnostic tools, unbiased by the presence of
      comorbidities, are needed, especially to detect the early stages of diabetic
      complications. OBJECTIVES: The aim of the study was to analyze changes in urinary
      protein excretion based on the stage of DKD using quantitative proteomics.
      PATIENTS AND METHODS: A total of 27 healthy controls were age- and sex-matched to
      72 diabetes patients classified into 3 groups: no signs of retinopathy or
      nephropathy (n = 33), retinopathy but no microalbuminuria (n = 15), and diabetic
      nephropathy (DN) based on overt albuminuria or microalbuminuria with retinopathy
      (n = 24). To assess the intergroup differences, samples were partially pooled,
      tagged using 8-plex iTRAQ reagents, and the resulting peptide mixture was
      resolved by isoelectrofocusing. The obtained fractions were analyzed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Data were analyzed using the
      MASCOT software and dedicated in-house proteomic data analysis programs. RESULTS:
      The changes in the urine proteome following DKD progression involved some known
      protein markers of DN and several other proteins. Decreased levels of some
      proteins are presumably related to impaired secretory function of other organs
      affected by diabetes. In particular, a diminished excretion of pancreatic amylase
      and deoxyribonuclease I suggested exocrine pancreatic insufficiency (EPI),
      coexisting with type 2 diabetes. CONCLUSIONS: A decrease in the urinary excretion
      of some pancreatic enzymes suggests EPI associated with diabetes. This hypothesis
      is yet to be verified; nevertheless, renal and extrarenal confounders must be
      considered when interpreting the results of quantitative urinary proteomics.  

PMID- 25578434
TI  - Giant electrocaloric effect in ferroelectric nanotubes near room temperature.
AB  - Ferroelectric perovskite oxides possess large electrocaloric effect, but only at
      high temperature, which limits their potential as next generation solid state
      cooling devices. Here, we demonstrate from phase field simulations that a giant
      adiabatic temperature change exhibits near room temperature in the strained
      ferroelectric PbTiO3 nanotubes, which is several times in magnitude larger than
      that of PbTiO3 thin films. Such giant adiabatic temperature change is attributed
      to the extrinsic contribution of unusual domain transition, which involves a
      dedicated interplay among the electric field, strain, temperature and
      polarization. Careful selection of external strain allows one to harness the
      extrinsic contribution to obtain large adiabatic temperature change in
      ferroelectric nanotubes near room temperature. Our finding provides a novel
      insight into the electrocaloric response of ferroelectric nanostructures and
      leads to a new strategy to tailor and improve the electrocaloric properties of
      ferroelectric materials through domain engineering.

PMID- 25578433
TI  - Placebo-controlled clinical trials: how trial documents justify the use of
      randomisation and placebo.
AB  - BACKGROUND: Randomised clinical trials (RCTs) involve procedures such as
      randomisation, blinding, and placebo use, which are not part of standard medical
      care. Patients asked to participate in RCTs often experience difficulties in
      understanding the meaning of these and their justification. METHODS: We reviewed
      RCT protocols, statements of the principal investigator (PI), and participant
      information materials, as submitted for opinion to a research ethics committee.
      We evaluated how the justification for the use of placebo was described in these
      documents and how the participants had been informed about randomisation, placebo
      use, and the possible risks of receiving placebo. RESULTS: In total, 52 RCTs were
      identified. Eighteen of the study protocols (35%) provided some rationale for the
      use of placebo. In 15 (29%) of the statements, the PI had provided justification
      for its use. Possible risks related to placebo use were described in nine (17%)
      of the statements. An explanation as to why placebo was necessary featured in
      only 12 (23%) of the sets of participant-information materials, and only six
      (12%) of the documents discussed the possible risks associated with placebo.
      CONCLUSIONS: The justification of placebo control was inadequately described in
      the RCT study protocols, by principal or national co-ordinating investigators,
      and in participant-information documents. Furthermore, possible health-related
      risks associated with the use of placebo were poorly explained in the participant
      information documents. Ethics committes and study participants need to be better
      informed of the rationale for the use of placebo, along with the associated
      risks.

PMID- 25578435
TI  - Anticonvulsant and neurological profile of benzothiazoles: a mini-review.
AB  - From last few years research work on heterocyclic compound and their derivatives
      has been increasing. Benzothiazole molecule has a heterocyclic structure, basic
      in nature with wide variety of active sites. As a small molecule, it contains
      electronegative atoms due to which it is feasible for other moieties to form
      conjugates. Referring to the bioorganic and medicinal chemistry, the moiety has
      potential to give active pharmacophores to develop new therapeutically important
      compounds. Benzothiazole derivatives were found to exhibit efficacy against some
      very serious diseases like cancer, neurodegeneration, neuropathic pain,
      infectious diseases, epilepsy etc. In the present review, antiepileptic profile
      of benzothiazole derivatives is emphasized. 

PMID- 25578436
TI  - (7)Li in situ 1D NMR imaging of a lithium ion battery.
AB  - The spatial distribution of charge carriers in lithium ion batteries during
      current flow is of fundamental interest for a detailed understanding of transport
      properties and the development of strategies for future improvements of the
      electrolyte-electrode interface behaviour. In this work we explored the potential
      of (7)Li 1D in situ NMR imaging for the identification of concentration gradients
      under constant current load in a battery cell. An electrochemical cell based on
      PTFE body and a stack of glass microfiber discs that are soaked with a
      technically relevant electrolyte suitable for high-temperature application and
      squeezed between a Li metal and a nano-Si-graphite composite electrode was
      assembled to acquire (7)Li 1D in situ NMR profiles with an improved NMR pulse
      sequence as function of time and state of charge, thereby visualizing the course
      of ion concentration during charge and discharge. Surface localized changes of Li
      concentration were attributed to processes such as solid electrolyte interphase
      formation or full lithiation of the composite electrode. The method allows the
      extraction of lithium ion transport properties. 

PMID- 25578437
TI  - Abnormal serum calcium levels are associated with clinical response to
      maximization of heart failure therapy.
AB  - INTRODUCTION: Abnormal serum calcium levels are associated with adverse
      cardiovascular effects. Therapy of heart failure (HF) may result in urinary
      calcium excretion and calcium apposition to bones, and consequently, in calcemia.
      OBJECTIVES: The aim of the study was to assess the prevalence of abnormal calcium
      levels in the blood of patients receiving maximized HF therapy, to explore
      clinical and laboratory determinants of abnormal serum calcium levels, and to
      analyze the relation of abnormal calcium levels to prognosis. PATIENTS AND
      METHODS: The study included 722 patients with HF classified as New York Heart
      Association (NYHA) classes III-IV at baseline (age 53 +/-10 years, 13% of women),
      who underwent HF therapy optimization to maximum tolerated doses. RESULTS: After
      therapy maximization, the NYHA class improved in 66.7% of the patients, while it
      did not change in 31.0% and worsened in 2.4%. Hypocalcemia occurred in 166
      patients (22.9%) and was more prevalent in patients in whom the NYHA class
      improved. Hypercalcemia was diagnosed in 63 patients (8.7%) and was more common
      in patients with no functional improvement or worsening of the NYHA class. This
      effect was independent of age, sex, etiology of HF, body mass index, kidney
      function, or the use of thiazides. Hypercalcemia was associated with increased
      catabolism, hemodynamic compromise, more intensive inflammation, and lower bone
      mineral density. Lower albumin and higher phosphorus levels, were significant
      predictors of hypercalcemia, independently of kidney function. Hypocalcemia was
      associated with reduced catabolism, higher albumin and lower phosphorus levels,
      use of thiazides, and smoking history. Neither hypocalcemia nor hypercalcemia was
      associated with poor prognosis. CONCLUSIONS: Our study shows that abnormal serum
      calcium levels are associated with a clinical response to treatment maximization
      in patients with HF. Mild hypocalcemia after maximization of therapy is not
      associated with poorer prognosis. Hypercalcemia is associated with lack of
      response to treatment, and its prognostic value remains unclear.  

PMID- 25578445
TI  - Dopamine agonists early monotherapy for the delay of development of levodopa
      induced dyskinesias.
AB  - Dyskinesias are common, often disabling motor complications emerging in
      Parkinson's disease following chronic levodopa treatment. Common views associate
      the development of dyskinesias both with progressive loss of striatal dopamine
      nerve terminals and with intermittent delivery of the short half-life levodopa.
      Thus, according to continuous dopaminergic stimulation theory, dopamine agonists
      having half-lifes longer than levodopa would minimize the risk of the development
      of dyskinesias. The article highlights some interesting aspects of the clinical
      trials testing dopamine agonists monotherapy as a strategy that can reduce the
      risk of motor complications, and raises some concerns in terms of their early use
      in Parkinson's disease treatment to prevent or delay dyskinesia. Finally, we
      emphasize the need for reconsideration of arguments against use of levodopa as a
      starting therapy for Parkinson's disease. 

PMID- 25578446
TI  - Modulation of antigen presentation by intracellular trafficking.
AB  - Processing and loading of antigen into major histocompatibility complex molecules
      (MHC) occurs in specific intracellular compartments. Accessing MHC loading
      compartments requires trafficking via specific pathways, some of which have yet
      to be fully characterized. For MHC I, cross-presentation involves antigen
      trafficking to a specialised compartment. We review the features of this
      compartment and how it is accessed by different mechanisms of antigen capture and
      internalization. We also summarize advances in understanding how antigen
      efficiently accesses the MHC II loading compartment, with particular focus on the
      role of autophagy. Understanding the mechanisms that control how antigen is
      trafficked to specific compartments for loading and presentation is crucial if
      these pathways are to be manipulated more effectively in settings of vaccination.

PMID- 25578447
TI  - Expression quantitative trait Loci acting across multiple tissues are enriched in
      inherited risk for coronary artery disease.
AB  - BACKGROUND: Despite recent discoveries of new genetic risk factors, the majority
      of risk for coronary artery disease (CAD) remains elusive. As the most proximal
      sensor of DNA variation, RNA abundance can help identify subpopulations of
      genetic variants active in and across tissues mediating CAD risk through gene
      expression. METHODS AND RESULTS: By generating new genomic data on DNA and RNA
      samples from the Stockholm Atherosclerosis Gene Expression (STAGE) study, 8156
      cis-acting expression quantitative trait loci (eQTLs) for 6450 genes across 7 CAD
      relevant tissues were detected. The inherited risk enrichments of tissue-defined
      sets of these eQTLs were assessed using 2 independent genome-wide association
      data sets. eQTLs acting across increasing numbers of tissues were found
      increasingly enriched for CAD risk and resided at regulatory hot spots. The risk
      enrichment of 42 eQTLs acting across 5 to 6 tissues was particularly high (<=7.3
      fold) and confirmed in the combined genome-wide association data from Coronary
      Artery Disease Genome Wide Replication And Meta-Analysis Consortium. Sixteen of
      the 42 eQTLs associated with 19 master regulatory genes and 29 downstream gene
      sets (n>30) were further risk enriched comparable to that of the 153 genome-wide
      association risk single-nucleotide polymorphisms established for CAD (8.4-fold
      versus 10-fold). Three gene sets, governed by the master regulators FLYWCH1,
      PSORSIC3, and G3BP1, segregated the STAGE patients according to extent of CAD,
      and small interfering RNA targeting of these master regulators affected
      cholesterol-ester accumulation in foam cells of the THP1 monocytic cell line.
      CONCLUSIONS: eQTLs acting across multiple tissues are significant carriers of
      inherited risk for CAD. FLYWCH1, PSORSIC3, and G3BP1 are novel master regulatory
      genes in CAD that may be suitable targets.

PMID- 25578464
TI  - Interplay between water uptake, ion interactions, and conductivity in an e-beam
      grafted poly(ethylene-co-tetrafluoroethylene) anion exchange membrane.
AB  - We demonstrate that the true hydroxide conductivity in an e-beam grafted
      poly(ethylene-co-tetrafluoroethylene) [ETFE] anion exchange membrane (AEM) is as
      high as 132 mS cm(-1) at 80  degrees C and 95% RH, comparable to a proton
      exchange membrane, but with very much less water present in the film. To
      understand this behaviour we studied ion transport of hydroxide, carbonate,
      bicarbonate and chloride, as well as water uptake and distribution. Water uptake
      of the AEM in water vapor is an order of magnitude lower than when submerged in
      liquid water. In addition (19)F pulse field gradient spin echo NMR indicates that
      there is little tortuosity in the ionic pathways through the film. A complete
      analysis of the IR spectrum of the AEM and the analyses of water absorption using
      FT-IR led to conclusion that the fluorinated backbone chains do not interact with
      water and that two types of water domains exist within the membrane. The
      reduction in conductivity was measured during exposure of the OH(-) form of the
      AEM to air at 95% RH and was seen to be much slower than the reaction of CO2 with
      OH(-) as the amount of water in the film determines its ionic conductivity and at
      relative wet RHs its re-organization is slow. 

PMID- 25578465
TI  - Non-aqueous semi-solid flow battery based on Na-ion chemistry. P2-type
      Na(x)Ni(0.22)Co(0.11)Mn(0.66)O(2)-NaTi2(PO4)3.
AB  - We report the first proof of concept for a non-aqueous semi-solid flow battery
      (SSFB) based on Na-ion chemistry using P2-type NaxNi0.22Co0.11Mn0.66O2 and
      NaTi2(PO4)3 as positive and negative electrodes, respectively. This concept opens
      the door for developing a new low-cost type of non-aqueous semi-solid flow
      batteries based on the rich chemistry of Na-ion intercalating compounds. 

PMID- 25578459
TI  - Following Natures Lead: On the Construction of Membrane-Inserted Toxins in Lipid
      Bilayer Nanodiscs.
AB  - Bacterial toxin or viral entry into the cell often requires cell surface binding
      and endocytosis. The endosomal acidification induces a limited
      unfolding/refolding and membrane insertion reaction of the soluble toxins or
      viral proteins into their translocation competent or membrane inserted states. At
      the molecular level, the specific orientation and immobilization of the pre
      transitioned toxin on the cell surface is often an important prerequisite prior
      to cell entry. We propose that structures of some toxin membrane insertion
      complexes may be observed through procedures where one rationally immobilizes the
      soluble toxin so that potential unfolding <-> refolding transitions that occur
      prior to membrane insertion orientate away from the immobilization surface in the
      presence of lipid micelle pre-nanodisc structures. As a specific example, the
      immobilized prepore form of the anthrax toxin pore translocon or protective
      antigen can be transitioned, inserted into a model lipid membrane (nanodiscs),
      and released from the immobilized support in its membrane solubilized form. This
      particular strategy, although unconventional, is a useful procedure for
      generating pure membrane-inserted toxins in nanodiscs for electron microscopy
      structural analysis. In addition, generating a similar immobilized platform on
      label-free biosensor surfaces allows one to observe the kinetics of these acid
      induced membrane insertion transitions. These platforms can facilitate the
      rational design of inhibitors that specifically target the toxin membrane
      insertion transitions that occur during endosomal acidification. This approach
      may lead to a new class of direct anti-toxin inhibitors. 

PMID- 25578466
TI  - Effect of mandibular advancement splint treatment on tongue shape in obstructive
      sleep apnea.
AB  - PURPOSE: Mandibular advancement splints (MAS) can effectively treat obstructive
      sleep apnea (OSA); however, treatment response is variable, and the mechanisms
      behind differences in treatment outcomes are still not well understood. The aims
      of this study were (1) to assess the effects of MAS on tongue shape and (2) to
      compare tongue shape changes with MAS between treatment responders and
      nonresponders. METHODS: Sixty-eight adults with symptomatic mild to severe OSA
      were included. A custom-made MAS was provided to patients, and treatment outcome
      was determined by polysomnography. Two-dimensional tongue measurements were
      evaluated using sagittal and axial MRI image slices without and with MAS in situ.
      Tongue measurements of height, length, width, area, and shape (height/length)
      were collected. Additional measurements of surrounding upper airway structures,
      soft palate length width and area and upper airway area, length and minimum width
      were measured on sagittal image slices. RESULTS: Based on polysomnography with
      MAS in situ, 47 patients were classified as responders (>=50% reduction in apnea
      hypopnea index [AHI] from baseline), and 21 were nonresponders (<50% AHI
      reduction). There was no change in sagittal tongue area with insertion of MAS,
      although there was a change in most of parameters of tongue shape. Responders
      showed a greater decrease in tongue length with MAS in situ compared to
      nonresponders (-0.64 +/- 0.46 vs -0.32 +/- 0.51 cm, p = 0.016). CONCLUSION: This
      study reports a detailed two-dimensional analysis of tongue dimensions as well as
      assessment of adjacentsoft palate shape and upper airway structures without and
      with MAS treatment for OSA. Our finding suggests that MAS does induce changes in
      tongue shape. MAS treatment responders showed a greater decrease in tongue length
      (between the tongue tip and hyoid bone) with MAS in situ; whether differences in
      alteration of tongue position with MAS explain differences in treatment response
      requires further investigation.

PMID- 25578467
TI  - Hybrid optical fiber add-drop filter based on wavelength dependent light coupling
      between micro/nano fiber ring and side-polished fiber.
AB  - In this paper, we report our experimental study on directly coupling a micro/nano
      fiber (MNOF) ring with a side-polished fiber(SPF). As a result of the study, the
      behavior of an add-drop filter was observed. The demonstrated add-drop filter
      explored the wavelength dependence of light coupling between a MNOF ring and a
      SPF. The characteristics of the filter and its performance dependence on the MNOF
      ring diameter were investigated experimentally. The investigation resulted in an
      empirically obtained ring diameter that showed relatively good filter
      performance. Since light coupling between a (MNOF) and a conventional single mode
      fiber has remained a challenge in the photonic integration community, the present
      study may provide an alternative way to couple light between a MNOF device and a
      conventional single mode fiber based device or system. The hybridization approach
      that uses a SPF as a platform to integrate a MNOF device may enable the
      realization of other all-fiber optical hybrid devices. 

PMID- 25578469
TI  - Surgical and audiological evaluation of the Baha BA400.
AB  - OBJECTIVE: Despite extensive soft tissue reduction, the most common complications
      associated with bone-anchored hearing aid systems, also known as bone-anchored
      hearing implants, are related to adverse skin reactions around the abutment. The
      necessary soft tissue reduction also adds complexity to the surgical procedure.
      This study aimed to evaluate the surgical and audiological outcomes of a new
      connective interface of the CochlearTM Baha(r) BA400 device implanted using the
      one-stage surgical technique. METHOD: A multicentre, retrospective case series is
      presented, including data collected from three tertiary care institutions.
      RESULTS: In total, 16 patients who had undergone bone-anchored hearing aid
      surgery over a 10- to 12-month period were assessed for hearing performance,
      implant stability and surgical complications. CONCLUSION: This case series
      indicates that new abutments with a hydroxyapatite coating can be implanted
      percutaneously without soft tissue reduction. Furthermore, device implantation
      using this surgical technique may have some advantages compared with a
      conventional device and procedure combination over 12- to 16-months of follow up.

PMID- 25578468
TI  - Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a
      critical review.
AB  - Herein we will review the role of glycans in the immune system. Specific topics
      covered include: the glycosylation sites of IgE, IgM, IgD, IgE, IgA, and IgG; how
      glycans can encode "self" identity by functioning as either danger associated
      molecular patterns (DAMPs) or self-associated molecular patterns (SAMPs); the
      role of glycans as markers of protein integrity and age; how the glycocalyx can
      dictate the migration pattern of immune cells; and how the combination of Fc N
      glycans and Ig isotype dictate the effector function of immunoglobulins. We
      speculate that the latter may be responsible for the well-documented association
      between alterations of the serum glycome and autoimmunity. Due to technological
      limitations, the extent of these autoimmune-associated glycan alterations and
      their role in disease pathophysiology has not been fully elucidated. Thus, we
      also review the current technologies available for glycan analysis, placing an
      emphasis on Multiple Reaction Monitoring (MRM), a rapid high-throughput
      technology that has great potential for glycan biomarker research. Finally, we
      put forth The Altered Glycan Theory of Autoimmunity, which states that each
      autoimmune disease will have a unique glycan signature characterized by the site
      specific relative abundances of individual glycan structures on immune cells and
      extracellular proteins, especially the site-specific glycosylation patterns of
      the different immunoglobulin(Ig) classes and subclasses.

PMID- 25578474
TI  - HIF-1alpha is required for hematopoietic stem cell mobilization and 4-prolyl
      hydroxylase inhibitors enhance mobilization by stabilizing HIF-1alpha.
AB  - Many patients with hematological neoplasms fail to mobilize sufficient numbers of
      hematopoietic stem cells (HSCs) in response to granulocyte colony-stimulating
      factor (G-CSF) precluding subsequent autologous HSC transplantation. Plerixafor,
      a specific antagonist of the chemokine receptor CXCR4, can rescue some but not
      all patients who failed to mobilize with G-CSF alone. These refractory poor
      mobilizers cannot currently benefit from autologous transplantation. To discover
      alternative targetable pathways to enhance HSC mobilization, we studied the role
      of hypoxia-inducible factor-1alpha (HIF-1alpha) and the effect of HIF-1alpha
      pharmacological stabilization on HSC mobilization in mice. We demonstrate in mice
      with HSC-specific conditional deletion of the Hif1a gene that the oxygen-labile
      transcription factor HIF-1alpha is essential for HSC mobilization in response to
      G-CSF and Plerixafor. Conversely, pharmacological stabilization of HIF-1alpha
      with the 4-prolyl hydroxylase inhibitor FG-4497 synergizes with G-CSF and
      Plerixafor increasing mobilization of reconstituting HSCs 20-fold compared with G
      CSF plus Plerixafor, currently the most potent mobilizing combination used in the
      clinic. 

PMID- 25578475
TI  - CDK9 inhibition by dinaciclib potently suppresses Mcl-1 to induce durable
      apoptotic responses in aggressive MYC-driven B-cell lymphoma in vivo.

PMID- 25578477
TI  - Effect of Heating Method on Alteration of Protein Molecular Structure in
      Flaxseed: Relationship with Changes in Protein Subfraction Profile and Digestion
      in Dairy Cows.
AB  - This study evaluated the effect of heating methods on alteration of protein
      molecular structure in flaxseed (Linum usitatissimum L.) in relation to changes
      in protein subfraction profile and digestion in dairy cows. Seeds from two
      flaxseed varieties, sampled from two replicate plots at two locations, were
      evaluated. The seeds were either maintained in their raw state or heated in an
      air-draft oven (dry heating) or autoclave (moist heating) for 60 min at 120 
      degrees C or by microwave irradiation (MIR) for 5 min. Compared to raw seeds,
      moist heating decreased (P < 0.05) soluble protein (SP) content [56.5 +/- 5.55 to
      25.9 +/- 6.16% crude protein (CP)] and increased (P < 0.05) rumen undegraded
      protein (RUP) content (36.0 +/- 5.19 to 46.9 +/- 2.72% CP) and intestinal
      digestibility of RUP (61.0 +/- 2.28 to 63.8 +/- 2.67% RUP). Dry heating did not
      alter (P > 0.05) the protein subfraction profile and rumen degradation kinetics,
      whereas MIR increased (P < 0.05) the RUP content from 36.0 +/- 5.19 to 40.4 +/-
      4.67% CP. The MIR and dry heating did not alter (P > 0.05) the amide I to amide
      II ratio, but moist heating decreased (P < 0.05) both the amide I to amide II
      ratio and alpha-helix-to-beta-sheet ratio. Regression equations based on protein
      molecular spectral intensities provided high prediction power for estimation of
      heat-induced changes in SP (R2 = 0.62), RUP (R2 = 0.71), and intestinal
      digestibility of RUP (R2 = 0.72). Overall, heat-induced changes in protein
      nutritive value and digestion were strongly associated with heat-induced
      alteration in protein molecular structures.

PMID- 25578476
TI  - BIN1 tumor suppressor regulates Fas/Fas ligand-mediated apoptosis through c-FLIP
      in cutaneous T-cell lymphoma.
AB  - The bridging integrator 1 (BIN1) tumor suppressor encodes multiple alternatively
      spliced isoforms implicated in DNA repair, cell-cycle control, apoptosis and
      membrane dynamics. BIN1 attenuation has been reported in several solid tumors;
      however, the role of BIN1 in lymphomagenesis remains unexplored. We recently
      demonstrated that BIN1 transcript levels are significantly downregulated in
      CD4(+)CD7(-) Sezary cells from patients with Sezary syndrome (SS), a subtype of
      cutaneous T-cell lymphoma (CTCL). We have now demonstrated that restored BIN1
      expression in CTCL cells leads to a significant reduction in cell proliferation,
      an increase in spontaneous and Fas/Fas ligand (Fas/FasL)-induced apoptosis in
      vitro and inhibition of tumorigenic activity of CTCL cells in vivo.
      Interestingly, restoration of BIN1 expression in CTCL cells downregulates the
      expression of c-FLIP, an important inhibitor of Fas/FasL-mediated apoptosis, and
      activates the caspase cascade; these phenotypes can be rescued by knockdown of
      BIN1. Importantly, significantly reduced BIN1 expression and increased c-FLIP
      expression are observed in primary CTCL patient samples, and high BIN1 and low c
      FLIP mRNA levels correlate with better survival rate in SS patients. These
      results indicate that BIN1 regulates Fas/FasL-mediated apoptosis through c-FLIP
      and that BIN1 deficiency may have an important role in CTCL pathogenesis by
      causing apoptosis resistance. Thus BIN1 and c-FLIP represent potential
      therapeutic targets in CTCL. 

PMID- 25578480
TI  - Editorial: biochemical targets and biomarkers for central nervous system
      protection and monitoring.

PMID- 25578479
TI  - Tissue specific loss of A-type lamins in the gastrointestinal epithelium can
      enhance polyp size.
AB  - The nuclear lamina, comprised of the A and B-type lamins, is important in
      maintaining nuclear shape and in regulating key nuclear functions such as
      chromatin organization and transcription. Deletion of the A-type lamins results
      in genome instability and many cancers show altered levels of A-type lamin
      expression. Loss of function mutations in the mouse Lmna gene result in early
      postnatal lethality, usually within 3-5 weeks of birth making an analysis of the
      role of lamins in carcinogenesis difficult. To circumvent early lethality, and
      determine the role of the A-type lamins in specific tissues in older mice we
      derived a conditional allele of Lmna(FL/FL) (floxed). Lmna(FL/FL) was
      specifically deleted in the gastrointestinal (GI) epithelium by crossing the
      Lmna(FL/FL) mice with Villin-Cre mice. Mice lacking Lmna in the GI are overtly
      normal with no effects on overall growth, longevity or GI morphology. On a GI
      specific sensitized (Apc(Min/+)) background, polyp numbers are unchanged, but
      polyp size is slightly increased, and only in the duodenum. Our findings reveal
      that although A-type lamins are dispensable in the postnatal GI epithelium, loss
      of Lmna under malignant conditions may, to a limited extent, enhance polyp size
      indicating that A-type lamins may regulate cell proliferation in the transformed
      GI epithelium. 

PMID- 25578478
TI  - Decellularized ECM effects on human mesenchymal stem cell stemness and
      differentiation.
AB  - Microenvironment extracellular matrices (ECMs) influence cell adhesion,
      proliferation and differentiation. The ECMs of different microenvironments have
      distinctive compositions and architectures. This investigation addresses effects
      ECMs deposited by a variety of cell types and decellularized with a cold-EDTA
      protocol have on multipotent human mesenchymal stromal/stem cell (hMSC) behavior
      and differentiation. The cold-EDTA protocol removes intact cells from ECM, with
      minimal ECM damage and contamination. The decellularized ECMs deposited by
      cultured hMSCs, osteogenic hMSCs, and two smooth muscle cell (SMC) lines were
      tested for distinctive effects on the behavior and differentiation of early
      passage ('naive') hMSC plated and cultured on the decellularized ECMs. Uninduced
      hMSC decellularized ECM enhanced naive hMSC proliferation and cell motility while
      maintaining stemness. Decellularized ECM deposited by osteogenic hMSCs early in
      the differentiation process stimulated naive hMSCs osteogenesis and substrate
      biomineralization in the absence of added dexamethasone, but this osteogenic
      induction potential was lower in ECMs decellularized later in the osteogenic hMSC
      differentiation process. Decellularized ECMs deposited by two smooth muscle cell
      lines induced naive hMSCs to become smooth muscle cell-like with distinctive
      phenotypic characteristics of contractile and synthetic smooth muscle cells. This
      investigation demonstrates a useful approach for obtaining functional cell
      deposited ECM and highlights the importance of ECM specificity in influencing
      stem cell behavior. 

PMID- 25578481
TI  - Coiled Impella Drive Line in the Left Ventricle: A Rare Complication of a Left
      Ventricular Assist Device.

PMID- 25578482
TI  - Successful removal of uncoiled J-tip guidewire.

PMID- 25578483
TI  - HIV/AIDS and rheumatoid arthritis.
AB  - The acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by
      the human immunodeficiency virus (HIV). It was first recognized in the United
      States in 1981, and the HIV/AIDS epidemic has since spread to affect all
      countries. The interface of HIV/AIDS with opportunistic infectious diseases is
      well characterized, but further research is required into the concurrence of
      other chronic diseases. The objective of this review was to identify possible
      interferences of HIV infection in the diagnosis and management of rheumatoid
      arthritis (RA). A review of the available evidence was conducted using the GRADE
      approach. Overall, the quality of evidence was low. Our main conclusions were:
      (1) the occurrence of rheumatoid-like arthritis in patients with HIV/AIDS is
      quite rare; therefore, it is not recommended that HIV infection be considered
      routinely as a differential diagnosis in this condition (C2); (2) HIV infection
      may lead to rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti
      CCP) antibody positivity, but usually at low titers (C1); (3) RA might cause
      false-positive HIV serology and ELISA seems to be a more specific test for HIV in
      patients with RA (C2); (4) RA and AIDS may coexist, even in cases of severe
      immunosuppression (C1); (5) RA emergence may seldom occur during or after immune
      reconstitution (C1); and (6) there is insufficient safety data to recommend use
      of specific disease-modifying antirheumatic drugs (DMARDs) in RA patients with
      HIV/AIDS. Therefore, these drugs should be used cautiously (C1).

PMID- 25578484
TI  - Molecular mechanism of myoglobin autoxidation: insights from computer
      simulations.
AB  - Myoglobin (Mb) and hemoglobin have the biological ability to carry/store oxygen
      (O2), a property which requires its heme iron atom to be in the ferrous--Fe(II)-
      state. However, the thermodynamically stable state in the presence of O2 is
      Fe(III) and thus the oxidation rate of a globin is a critical parameter related
      to its function. Mb has been extensively studied and many mutants have been
      characterized regarding its oxygen mediated oxidation (i.e., autoxidation) rates.
      Site directed mutants in residues 29 (B10), which shapes the distal cavity, and
      64 (E7), the well-known histidine gate, have been shown to display a wide range
      of autoxidation rate constants. In this work, we have thoroughly studied the
      mechanism underlying the autoxidation process by means of state-of-the-art
      computer simulation methodologies, using Mb and site directed mutants as
      benchmark cases. Our results explain the observed autoxidation rate tendencies in
      different variants of Mb, L29F < wt < L29A = H64Q < H64F < H64A, and shed light
      on several aspects of the reaction at the atomic level. First, water access to
      the distal pocket is a key event and the observed acid catalysis relies on HisE7
      protonation and opening of the His gate to allow water access, rather than
      protonation of the oxy heme itself. Our results also suggest that the basic
      mechanism, i.e., superoxide displacement by hydroxide anion, is energetically
      more feasible. Finally, we confirmed that distal hydrogen bonds protect the oxy
      complex from autoxidation.

PMID- 25578486
TI  - Site-specific tagging proteins via a rigid, stable and short thiolether tether
      for paramagnetic spectroscopic analysis.
AB  - Increasing the stability of protein bioconjugates and improving the resolution of
      protein complexes is important for spectroscopic analysis in structural biology.
      The reaction of phenylsulfonated pyridine derivatives and protein thiols
      generates a stable, rigid and short thiolether tether, which is valuable in high
      resolution spectroscopic measurements. 

PMID- 25578485
TI  - BrainNet Europe's Code of Conduct for brain banking.
AB  - Research utilizing human tissue and its removal at post-mortem has given rise to
      many controversies in the media and posed many dilemmas in the fields of law and
      ethics. The law often lacks clear instructions and unambiguous guidelines. The
      absence of a harmonized international legislation with regard to post-mortem
      medical procedures and donation of tissue and organs contributes to the
      complexity of the issue. Therefore, within the BrainNet Europe (BNE) consortium,
      a consortium of 19 European brain banks, we drafted an ethical Code of Conduct
      for brain banking that covers basic legal rules and bioethical principles
      involved in brain banking. Sources include laws, regulations and guidelines
      (Declarations, Conventions, Recommendations, Guidelines and Directives) issued by
      international key organizations, such as the Council of Europe, European
      Commission, World Medical Association and World Health Organization. The Code of
      Conduct addresses fundamental topics as the rights of the persons donating their
      tissue, the obligations of the brain bank with regard to respect and observance
      of such rights, informed consent, confidentiality, protection of personal data,
      collections of human biological material and their management, and transparency
      and accountability within the organization of a brain bank. The Code of Conduct
      for brain banking is being adopted by the BNE network prior to being enshrined in
      official legislation for brain banking in Europe and beyond. 

PMID- 25578487
TI  - Tadpole-like artificial micromotor.
AB  - We describe a polymer-based artificial tadpole-like micromotor, which is
      fabricated through the electrospinning technique. By incorporating functional
      materials onto its surface or within its body, the resulting tadpole-like
      micromotor can not only move autonomously in an aqueous solution with a flexible
      tail, but also exhibit thermo- and magnetic responsive properties. 

PMID- 25578488
TI  - Examining choking in basketball: effects of game outcome and situational
      variables during last 5 minutes and overtimes.
AB  - This study examined choking in basketball by identifying the effects of game
      outcome and situational variables during the last 5 min. and overtimes of close
      games. The sample consisted of two 5 min. segments (last 5 min. of the game, n =
      147, of which 97 did not go into overtime; 5 min. of overtime, n = 50) drawn from
      147 games from the Spanish Professional Basketball League (2007 to 2011). The
      following game-related statistics were gathered: 3- and 2-point field goals and
      free-throws (both successful and unsuccessful), offensive and defensive rebounds,
      assists, recovered balls, turnovers, blocks (both made and received), and fouls
      committed and received. The results suggested the need to account for the
      temporal structure and multi-skilled nature of the task when devising appropriate
      interventions.

PMID- 25578489
TI  - Aluminum Trichloride Disorders Bile Acid Secretion and Induces Hepatocyte
      Apoptosis in Rats.
AB  - The aim of this study was to examine effects of aluminum trichloride (AlCl3) on
      the bile acid secretion and hepatocyte apoptosis in rats. Forty male Wistar rats
      (5 weeks old) weighed 110-120 g were orally exposed to AlCl3 at doses of 0, 64.18
      (1/20LD50), 128.36 (1/10LD50), and 256.72 (1/5LD50) mg/kg body weight in drinking
      water for 120 days. Each group had ten rats. The serum total bile acid (TBA)
      concentration, the early and total hepatocyte apoptosis indexes, and protein and
      mRNA expression of Bcl-2 and Bax were determined. The results showed that the
      serum TBA concentration, the early and total hepatocyte apoptosis indexes, and
      protein and mRNA expression of Bax increased, while protein and mRNA expression
      of Bcl-2 decreased in AlCl3-treated rats. The results indicate that AlCl3
      disorders bile acid secretion and induces hepatocyte apoptosis in rats.

PMID- 25578490
TI  - Microfluidic single sperm entrapment and analysis.
AB  - Selection of healthy spermatozoa is of crucial importance for the success rates
      of assisted reproduction technologies (ART) such as in vitro fertilization and
      intra-cytoplasmic sperm injection. Although sperm selection for ART procedures is
      predominantly based on sperm motility, successful fertilization is not predicted
      by good motility alone. For example, sperm characteristics such as the acrosome
      state and DNA integrity have shown significant impact on ART outcome. Although
      fertilization can be achieved with a single spermatozoon of high quality, current
      quality assessments are population-based and do not allow investigation of
      multiple sperm characteristics on a single spermatozoon simultaneously. In order
      to study sperm cells on the single cell level, we designed and characterized a
      PDMS microfluidic platform that allows single sperm entrapment. After spatially
      confining individual sperm cells within microfluidic cell traps, the cell
      viability, chromosomal content and acrosome state were studied. This platform is
      suitable for the analysis of individual sperm cells, which could be exploited for
      (non-invasive) sperm analysis and selection by impedance or Raman spectroscopy. 

PMID- 25578491
TI  - How to predict short- and long-term mortality in patients with pulmonary
      embolism?
AB  - Pulmonary embolism (PE) is a common disease with a considerable short- and long
      term risk of death. An adequate evaluation of the prognosis in patients with PE
      may guide decision making in terms of the intensity of the initial treatment
      during the acute phase, duration of treatment, and intensity of follow-up control
      visits in the long term. Patients with shock or persistent hypotension are at
      high risk of early mortality and may benefit from immediate reperfusion. Several
      tools are available to define the short-term prognosis of hemodynamically stable
      patients. The Pulmonary Embolism Severity Index (PESI) score, simplified PESI
      score, and N-terminal pro-B-type natriuretic peptide levels are particularly
      useful for identifying patients at low risk of early complications who might be
      safely treated at home. However, the identification of patients who are
      hemodynamically stable at diagnosis but are at a high risk of early complications
      is more challenging. The current guidelines recommended a multiparametric
      prognostic algorithm based on the clinical status and comorbidities.
      Unfortunately, only a few studies have evaluated the role of risk factors
      potentially affecting the long-term prognosis of these patients. The available
      studies suggest a potential role of the PESI score and troponin levels evaluated
      at the time of an index event. However, further studies are warranted to confirm
      these preliminary findings and to identify other long-term prognostic factors in
      this setting.   

PMID- 25578492
TI  - Genetic variations in monocarboxylate transporter genes as predictors of clinical
      outcomes in non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is characterized by poor prognosis and only a
      few molecular markers may be potentially used to predict clinical outcomes.
      Previous studies have demonstrated that monocarboxylate transporters (MCTs) play
      important roles in the development and progression of many cancers. The purpose
      of this study was to assess the effects of single nucleotide polymorphisms (SNPs)
      of MCT genes on prognosis of NSCLC patients in Chinese Han population. Nine
      functional SNPs in MCT1, MCT2, and MCT4 genes were selected and genotyped using
      Sequenom iPLEX genotyping system in 500 Chinese NSCLC patients receiving surgery.
      Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for
      the prognostic analysis. TT genotype of SNP rs1049434 (MCT1) was significantly
      associated with better overall survival (OS) (HR = 0.56, P = 0.026) and
      recurrence-free survival (RFS) (HR = 0.57, P = 0.016) of NSCLC patients. TT
      genotype of another SNP rs995343 (MCT2) exhibited an association with worse RFS
      of NSCLC patients (HR = 1.46, P =  .039). Unfavorable genotypes of SNP rs1049434
      and rs995343 showed a significant cumulative effect on OS and RFS of NSCLC
      patients. Moreover, we found that patients carrying AA+AT genotypes of rs1049434
      showed significant OS and RFS benefits from adjuvant chemotherapy, but those with
      TT genotype did not. Our findings suggest that SNPs in MCT1 and MCT2 genes may
      affect clinical outcomes and can be used to predict the response to adjuvant
      chemotherapy in NSCLC patients who received surgical treatment once validated in
      future study.

PMID- 25578493
TI  - Increased expression of miR-93 is associated with poor prognosis in head and neck
      squamous cell carcinoma.
AB  - MicroRNA-93-5p (miR-93) is a novel oncogenic microRNA (miRNA) and is elevated in
      diverse human malignancies. Aberrant expression and dysfunction of miR-93 are
      involved in many types of human tumours. However, the exact role of miR-93
      remains unclear in head and neck squamous cell carcinoma (HNSCC). The objective
      of this study is to determine the expression pattern and clinical significance of
      miR-93 in HNSCC. MiR-93 expression levels in 103 primary HNSCC tissues and 16
      corresponding non-cancerous epithelia were analysed by miRNA in situ
      hybridisation and correlated with the clinicopathological parameters and patient
      outcomes. Moreover, the expression of miR-93 was examined in four HNSCC cell
      lines and 17 pairs of HNSCC tissues and their corresponding adjacent tissues
      using quantitative real-time PCR (qRT-PCR). The miR-93 levels in HNSCC tissues
      and cell lines were significantly higher than those in the non-cancerous tissues.
      Notably, high miR-93 expression was significantly associated with T
      classification, lymph node metastasis and clinical stage. Kaplan-Meier survival
      analysis demonstrated that patients with high miR-93 expression had poorer
      overall survival than patients with low miR-93 expression. Multivariate Cox
      regression analysis revealed that miR-93 overexpression and lymph node metastasis
      were independent prognostic factors in patients with HNSCC. This study
      demonstrated that miR-93 expression was significantly increased in HNSCC tissue
      samples and cell lines and that miR-93 overexpression was associated with tumour
      progression, metastasis and poor prognosis in HNSCC patients. These results
      suggest that miR-93 may play a critical role in the initiation and progression of
      HNSCC, indicating that miR-93 may be a valuable marker for the prediction of
      metastasis and prognosis in HNSCC. 

PMID- 25578494
TI  - Down-regulation of TIMP-1 inhibits cell migration, invasion, and metastatic
      colonization in lung adenocarcinoma.
AB  - Tissue inhibitor metalloproteinase-1 (TIMP-1) is clinically associated with a
      poor prognosis for various cancers, but the roles of TIMP-1 in lung cancer
      metastasis are controversial. Our previous secretomic study revealed that TIMP-1
      is highly abundant in high invasiveness cells of lung adenocarcinoma. In the
      current study, TIMP-1 abundances in primary lung adenocarcinoma tissues, as
      revealed by immunohistochemistry, are significantly higher in patients with lymph
      invasion and distant metastasis than in those without. Receiver operating
      characteristic curve analyses suggest 73.7 and 86.2 % accuracy to separate
      patients with lymph node and distant metastasis and those without, respectively.
      Moreover, we demonstrate that the expression level of TIMP-1 positively
      associates with cell mobility, invasiveness, and metastatic colonization. Most
      notably, the novel mechanism in which TIMP-1 facilitates metastatic colonization
      through the mediation of pericellular polyFN1 assembly was revealed. In summary,
      this study presents novel functions of TIMP-1 in promoting cancer metastasis and
      suggests TIMP-1 is a potential tissue biomarker for lymph invasion and distant
      metastasis of lung adenocarcinoma.

PMID- 25578495
TI  - Plasma proteasomal chymotrypsin-like activity correlates with prostate cancer
      progression.
AB  - Previously, we demonstrated that inhibition of proteasomal chymotrypsin-like (CT
      like) activity in human prostate cancer (PCa) PC-3 cultures and PC-3 xenografts
      results in accumulation of ubiquitinated proteins, followed by induction of cell
      death. Studies have shown that plasma CT-like proteasomal activity may be a
      powerful biomarker for risk stratification in hematologic malignancies. We
      hypothesized that circulating proteasomes could also be used to stratify risk for
      patients with PCa. A total of 109 patients with suspected PCa underwent prostatic
      biopsies were enrolled. Subjects were divided into non-cancer, low-risk PCa, and
      high-risk PCa groups. Three different proteasomal activity markers (CT-like,
      caspase-like, and trypsin-like) were measured and compared among the three
      groups. The proteasomal target proteins, Ub-prs, Hsp70, Bax, and P27 in plasma
      and prostate tissues were also evaluated. Multivariate analysis was used to
      assess whether CT-like activity was a predictor of PCa progression. Only
      proteasomal CT-like activity in the high-risk group was statistically higher than
      in the non-cancer group (P < 0.05). The expression of Ub-prs, Hsp70, Bax, and P27
      protein was decreased in both plasma and PCa tissue of high-risk patients. CT
      like activity was found to be an independent predictor of high-risk PCa. Subjects
      with CT-like activity >=55 had a 2.15-fold higher risk of having high-risk PCa as
      compared to those with a CT-like activity of <55 (P = 0.021). We found CT-like
      activity to be an independent predictor of high-risk PCa, and as such, it may be
      a good candidate as a biomarker for high-risk PCa detection and stratification.

PMID- 25578496
TI  - miR-145 inhibits invasion and metastasis by directly targeting Smad3 in
      nasopharyngeal cancer.
AB  - MicroRNA-145 (miR-145) has been implicated in several cancers. However, its role
      in nasopharyngeal carcinoma (NPC) remains unclear. In this study, we proved that
      miR-145 was significantly downregulated in NPC and associated with NPC cell
      metastasis. Moreover, miR-145 suppressed Smad3 by directly binding to the 3'
      untranslated region (UTR) of Smad3. Knockdown of Smad3 in NPC cells inhibited
      cell migration and invasion, which was consistent with the effect of miR-145 in
      NPC cells. In addition, Smad3 expression was inversely correlated with miR-145
      level in clinical NPC samples. Taken together, our findings indicate that miR-145
      is a tumour suppressor that affects invasive and metastatic properties of NPC via
      the miR-145/Smad3 axis, leading us to propose that miR-145 overexpression might
      be a potential therapeutic strategy of NPC intervention.

PMID- 25578497
TI  - Extracellular cytochrome c as a biomarker for monitoring therapeutic efficacy and
      prognosis of non-small cell lung cancer patients.
AB  - Non-small cell lung cancer has a devastating prognosis, and markers enabling a
      precise prediction of therapy response have long remained scarce. Better
      treatment monitoring would allow an individual's more effective patient adjusted
      therapy with lesser side effects and good clinical outcomes. In the present
      study, we monitored the serum cytochrome c levels pre- and post-chemotherapy of
      non-small cell lung cancer patients. Using highly sensitive enzyme-linked
      immunosorbent assay, we evaluated cytochrome c levels in serum of 100 non-small
      cell lung cancer and 100 healthy controls. We observed about threefold lower
      serum cytochrome c level in newly diagnosed non-small cell lung cancer patients
      than healthy individuals. Patients in advanced stages and grade 3 histological
      differentiation showed significantly low level of serum cytochrome c, and the
      lower levels were associated with worse survival outcome of non-small cell lung
      cancer patients. In addition, serum cytochrome c level was observed to be more
      than 13-fold higher after first cycle of conventional chemotherapy, wherein
      patients with higher level of serum cytochrome c before any therapy showed better
      response to chemotherapy in terms of significantly higher level of serum
      cytochrome c after first cycle of chemotherapy than patients with low level of
      serum cytochrome c at the time of diagnosis. Detection of serum cytochrome c
      levels at the time of diagnosis may be useful in suggesting disease severity and
      prognosis of the non-small cell lung cancer patients. Monitoring of serum
      cytochrome c might also serve as a sensitive apoptotic marker in vivo reflecting
      chemotherapy-induced cell death burden in patients with non-small cell lung
      cancer.

PMID- 25578498
TI  - Efficient stereological approaches for the volumetry of a normal or enlarged
      spleen from MDCT images.
AB  - OBJECTIVES: To introduce efficient stereological approaches for estimating the
      volume of a normal or enlarged spleen from MDCT. METHODS: All study participants
      underwent an abdominal MDCT. The first group included 20 consecutive patients
      with splenomegaly and the second group consisted of 20 subjects with a normal
      spleen. Splenic volume estimations were performed using the stereological point
      counting method. Stereological assessments were optimized using the systematic
      slice sampling procedure. Planimetric measurements based on manual tracing of
      splenic boundaries on each slice were taken as reference values. RESULTS:
      Stereological analysis using five to eight systematically sampled slices provided
      enlarged splenic volume estimations with a mean precision of 4.9 +/- 1.0 % in a
      mean time of 2.3 +/- 0.4 min. A similar measurement duration and error was
      observed for normal splenic volume assessment using four to seven systematically
      selected slices. These stereological approaches slightly but insignificantly
      overestimated the volume of a normal and enlarged spleen compared to planimetry
      (P > 0.05) with a mean difference of -1.3 +/- 4.3 % and -2.7 +/- 5.2 %,
      respectively. The two methods were highly correlated (r >= 0.96). The variability
      of repeated stereological estimations was below 3.8 %. CONCLUSIONS: The proposed
      stereological approaches enable the rapid, reproducible, and accurate splenic
      volume estimation from MDCT data in patients with or without splenomegaly. KEY
      POINTS: * New efficient stereological approaches are proposed for spleen
      volumetry from MDCT * These volumetric approaches are applicable in patients with
      or without splenomegaly * Stereological splenic volume estimations from MDCT are
      rapid, reproducible, and accurate.

PMID- 25578502
TI  - Long-term culture of chicken primordial germ cells isolated from embryonic blood
      and production of germline chimaeric chickens.
AB  - Production of germline chimaeric chickens by the transfer of cultured primordial
      germ cells (PGC) is a useful system for germline manipulation. A novel culture
      system was developed for chicken PGC isolated from embryonic blood. The isolated
      PGC were cultured on feeder cells derived from chicken embryonic fibroblast. The
      cultured PGC formed colonies and they proliferated about 300-times during the
      first 30 days. The cultured PGC retained the ability to migrate to recipient
      gonads and were also chicken VASA homologue (CVH)-positive. Female PGC were
      present in the mixed-sex PGC populations cultured for more than 90 days and gave
      rise to viable offspring efficiently via germline chimaeric chickens. Male
      cultured PGC were transferred to recipient embryos and produced putative
      chimaeric chickens. The DNA derived from the cultured PGC was detected in the
      sperm samples of male putative chimaeric chickens, but no donor derived offspring
      were obtained. Donor-derived offspring were also obtained from germline chimaeric
      chickens by the transfer of frozen-thawed cultured PGC. The culture method for
      PGC developed in the present study is useful for manipulation of the germline in
      chickens, such as preservation of genetic resources and gene transfer. 

PMID- 25578503
TI  - Effect of melatonin or maternal nutrient restriction on vascularity and cell
      proliferation in the ovine placenta.
AB  - Previously we reported increased umbilical artery blood flow in ewes supplemented
      with melatonin from mid- to late-pregnancy, while maternal nutrient restriction
      decreased uterine artery blood flow. To further unravel these responses, this
      study was designed to assess placental cell proliferation and vascularity
      following supplementation with melatonin or maternal nutrient restriction. For
      the first experiment, 31 primiparous ewes were supplemented with 5mg of melatonin
      per day (MEL) or no melatonin (CON) and allocated to receive 100% (adequate fed;
      ADQ) or 60% (restricted; RES) of their nutrient requirements from day 50 to 130
      of gestation. To examine melatonin receptor dependent effects, a second
      experiment was designed utilizing 14 primiparous ewes infused with vehicle,
      melatonin, or luzindole (melatonin receptor 1 and 2 antagonist) from day 62 to 90
      of gestation. For experiment 1, caruncle concentrations of RNA were increased in
      MEL-RES compared to CON-RES. Caruncle capillary area density and average
      capillary cross-sectional area were decreased in MEL-RES compared to CON-RES.
      Cotyledon vascularity was not different across dietary treatments. For experiment
      2, placental cellular proliferation and vascularity were not affected by infusion
      treatment. In summary, melatonin interacted with nutrient restriction to alter
      caruncle vascularity and RNA concentrations during late pregnancy. Although
      melatonin receptor antagonism alters feto-placental blood flow, these receptor
      dependent responses were not observed in placental vascularity. Moreover,
      placental vascularity measures do not fully explain the alterations in
      uteroplacental blood flow. 

PMID- 25578504
TI  - Effect of nutritional state on semen characteristics, testicular size and serum
      testosterone concentration in Sanjabi ram lambs during the natural breeding
      season.
AB  - This experiment was conducted to investigate the effect of plane of nutrition on
      body weight, average daily gain, dry mater intake, semen characteristics, serum
      testosterone concentration and testicular circumference of Sanjabi ram lambs
      during the natural breeding season. Sanjabi ram lambs (n = 20) that were 8 months
      of age were penned under natural photoperiod at latitude 34 degrees 18'N for a
      period of 9 months. The control group (C, n = 10) received a diet consisting of
      80% alfalfa and 20% concentrate, providing 2.18 Mcal metabolizable energy and
      130.0 g /kg DM crude protein, whereas, treatment group (T, n = 10) was fed with
      65% alfalfa and 35% concentrate, providing 2.34 Mcal metabolizable energy and
      160.0 g/kg DM crude protein. Body weight, additive daily gain and feed intake in
      T group were significantly greater than those obtained in C group. Body weight
      and testicular circumference increased at a steady rate throughout the
      experiment. All semen variables (except percentage of abnormal sperm and semen
      pH), serum testosterone concentration and testicular circumference were
      positively influenced by nutritional state (P < 0.05). Interaction of nutritional
      state with season was found for semen volume, sperm concentration and abnormal
      sperm, but there was no interaction on the total sperm, progressive motility,
      live sperm, semen pH and semen index. It is concluded that the reproductive
      activity of growing Sanjabi ram lambs is affected by nutritional state. These
      results also demonstrated a monthly pattern in reproductive characteristics of
      Sanjabi ram lambs, independent of the nutritional state.

PMID- 25578505
TI  - Luteal changes after treatment with sub-luteolytic doses of prostaglandin
      (cloprostenol sodium) in cattle.
AB  - This study characterizes the physiological and morphological changes related to
      partial luteolysis in bovine corpus luteum (CL) after challenges with sub-doses
      of cloprostenol sodium on Day 6 (D6) of the estrous cycle. Cows (n =
      12/treatment) were treated as follows: Control (2 mL, saline, i.m.); 2XPGF (two
      treatments i.m. 500 MUg of cloprostenol sodium 2 h apart) and 1/6PGF (83.3 MUg of
      cloprostenol sodium, i.m., once). Plasma progesterone (P4) concentration, CL
      volume and blood flow were measured immediately before the treatments, then every
      8 h (h) for 48 h. In the Control, P4 concentrations were higher at 48 h than at 0
      h. P4 decreased 8h after 2XPGF treatment (P < 0.05), and remained low until the
      end of the trial. P4 decreased in 1/6PGF between 8 and 16 h (P < 0.05), then
      began to rebound at 24 h. Luteal volume was higher in Controls at 48 h than at 0
      h. Under 1/6PGF, luteal volume decreased at 24 h (P < 0.05) and began to rebound
      at 32 h. Luteal volume and blood flow were reduced starting at 24 and 32 h,
      respectively, after 2XPGF treatment (P < 0.05). In this study, we were able to
      describe the partial luteolysis phenomenon, induced by a treatment of a D6CL with
      cloprostenol sub-dose.

PMID- 25578506
TI  - Hormone supplementation protocol using estradiol benzoate and long-acting
      progesterone is efficient in maintaining pregnancy of anovulatory recipient mares
      during autumn transitional phase.
AB  - The present research sought to determine whether the administration of estradiol
      benzoate and long-acting progesterone to anovulatory recipient mares could
      maintain the pregnancy after embryo transfer during the autumn transitional
      phase. Recipient mares (n = 40) received the hormonal supplementation (treated
      group) whereas the other 36 served as a control. The control group consisted of
      mares having typical estrous cycles with ovulations, development of a viable
      corpus luteum and received one transferred embryo 5 days after ovulation.
      Hormonal administrations in the treated group started 8 days before the embryo
      transfer. During the first 3 days, the mares received estradiol benzoate (5 mg
      the first day, 3 mg the second day and 2 mg the third day). At Day 5 subsequent
      to ovulation, the mares received one administration of 1500 mg long-acting
      progesterone, and the same treatments occurred at the day of embryo transfer.
      Afterwards, treated mares also received 1500 mg long-acting progesterone every 7
      days until 120 days of gestation. For both control and treated groups, the
      recipient mares were classified as acceptable, marginally acceptable or
      unacceptable for embryo transfer, and the embryo quality was also determined. The
      pregnancy diagnosis in recipient mares was made at Days 13, 30 and 60 of
      pregnancy. While the pregnancy rate was greater (P < 0.05) in the treated than in
      the control group, the recipient classification did not influence pregnancy
      rates. In conclusion, pregnancy in anovulatory recipient mares during the autumn
      transitional phase can be achieved when estradiol benzoate and progesterone are
      administered.

PMID- 25578507
TI  - Simple balloon dilation for drug-eluting in-stent restenosis: an optical coherent
      tomography analysis.
AB  - BACKGROUND: Although drug-eluting stent (DES) has significantly reduced
      restenosis, the treatment of DES-in-stent restenosis (ISR) remains a challenge
      with high restenosis rate. METHODS: We examined whether morphologic appearance of
      restenosis tissue by optical coherent tomography (OCT) had an impact on outcomes
      after balloon angioplasty for DES-ISR. The morphologic appearance of restenosis
      tissue was qualitatively assessed for tissue structures such as homogeneous,
      layered, and heterogeneous patterns. RESULTS: Using OCT, 50 patients with DES-ISR
      were divided into 2 groups: 25 lesions with homogeneous or layered patterns
      (homo/layered group) and 25 lesions with heterogeneous patterns (hetero group).
      Acute gain was larger in the hetero group (1.33 +/- 0.41 mm vs. 1.06 +/- 0.32 mm
      in the homo/layered group, P = 0.03). On intravascular ultrasound analysis, post
      procedural percent neointimal area was smaller in the hetero group (27.4 +/- 9.2%
      vs. 34.0 +/- 11.2% in the homo/layered group, P = 0.05). Angiographic follow-up
      was performed in 37 lesions (74%). Follow-up minimal lumen diameter was larger in
      the hetero group (1.75 +/- 0.89 mm vs. 1.01 +/- 0.81 mm in the homo/layered
      group, P = 0.04). Target lesion revascularization rates tended to be lower in the
      hetero group (20% vs. 43% in the homo/layered group, P = 0.12). CONCLUSIONS:
      Balloon angioplasty was more effective for DES-ISR with heterogeneous tissue
      appearance than DES-ISR with homogeneous/layered tissue appearance. OCT
      assessment of DES-ISR morphology may be a useful adjunct in determining clinical
      strategies. Simple balloon dilatation is a possible treatment strategy for DES
      ISR lesions with a heterogeneous appearance on OCT images.

PMID- 25578508
TI  - Contribution of enrichments and resampling for sulfate reducing bacteria
      diversity assessment by high-throughput cultivation.
AB  - The development of new high-throughput cultivation methods aims to increase the
      isolation efficiency as compared to standard techniques that often require
      enrichment procedures to compensate the low microbial recovery. In the current
      study, estuarine sulfate-reducing bacteria were isolated using an anaerobic
      isolation procedure in 384-well microplates. Ninety-nine strains were recovered
      from initial sediments. Isolates were identified according to their partial 16S
      rRNA sequences and clustered into 13 phylotypes. Besides, the increase in species
      richness obtained through enrichments or resampling was investigated. Forty-four
      enrichment procedures were conducted and shifts in sulfate-reducing bacterial
      communities were investigated through dsrAB gene fingerprinting. Despite efforts
      in conducting numerous enrichment conditions only few of them were statistically
      different from initial sample. The cultural diversity obtained from 3 of the most
      divergent enrichments, as well as from resampled sediments equally contributed to
      raise the sulfate-reducing diversity up to 22 phylotypes. Enrichments (selection
      of metabolism) or resampling (transient populations and micro-heterogeneity) may
      still be helpful to assess new microbial phylotypes. Nevertheless, all the newly
      cultivated strains were all representatives of minor Operational Taxonomic Units
      and could eventually be recovered by maintaining high-throughput isolation effort
      from the initial sediments. 

PMID- 25578509
TI  - Comparison of five methods for direct extraction of surface proteins from
      Listeria monocytogenes for proteomic analysis by orbitrap mass spectrometry.
AB  - Extracts of surface proteins, with minimal artifacts from contaminating cytosolic
      components, are highly desirable for investigating surface factors involved in
      the attachment and formation of biofilms by bacteria that are problematic in
      commercial food processing facilities. In this study, we compared the protein
      profiles of the food pathogen, Listeria monocytogenes, recovered after applying
      different surface protein extraction methods compiled from the literature:
      trypsin-enzymatic shaving with BICAM/sucrose or Tris/sucrose buffers (Tryp B+S,
      Tryp T+S), Tris-buffered urea (UB), lithium chloride (LiCl) and Tris-buffered
      urea applied with hypotonic-stressed cells (UB-Ghost), and subjected them to
      liquid chromatography tandem mass spectrometry and protein identification. The
      data indicate that the UB-Ghost extraction method provides a cleaner extract of
      surface proteins including the predicted (this study and the literature) or
      validated members (literature) from L. monocytogenes. This was determined by an
      accumulative lower unique peptide number exhibited by mass spectrometry for total
      cytoplasmic proteins among different surface extracts, with a majority of
      proteins demonstrating hydrophilic properties. The extracted proteins were from
      different functional categories and have associations with the cell surface,
      intermediary metabolism, information pathways, or functionally unknown proteins
      as suggested by in silico analyses performed by other groups (Leger and
      ListiList). The utilization of an optimized method for surface protein extraction
      should greatly facilitate identification by LC-MS/MS that could be useful to
      anyone working on molecular proteomics of bacterial surfaces. 

PMID- 25578510
TI  - Contemporary Management of Medium-Sized (10-20 mm) Renal Stones: A Retrospective
      Multicenter Observational Study.
AB  - PURPOSE: To evaluate contemporary management approaches to medium-sized (10-20
      mm) renal stones. PATIENTS AND METHODS: A total of 935 patients treated for
      medium-sized renal stones (10-20 mm) between July 2012 and March 2014 were
      included in the study program. Contemporary minimally invasive approaches applied
      in the management of such stones were evaluated and compared. RESULTS: The cohort
      consisted of 561 male (60%) and 374 female (40%) patients. Of the 935 patients
      with medium-sized renal calculi, 535 (57.2%) were treated with shockwave
      lithotripsy (SWL), 201 (21.4%) with retrograde intrarenal surgery (RIRS), 110
      (11.7%) with minimally invasive percutaneous nephrolithotomy (miniperc), and the
      remaining 89 (11.7%) patients with micropercutaneous nephrolithotomy (microperc).
      In the SWL group, stones were located mostly in the pelvis (51%), while in the
      miniperc and microperc groups, they were located mainly in the lower pole (46%,
      53%, respectively). Stone-free rates after a single session were 77.2%, 86.1%,
      88.8%, and 83.6% in the SWL, RIRS, microperc, and miniperc groups, respectively.
      Although no serious complications (above Clavien level III) were noted in any of
      the groups evaluated, Clavien I to II complications were common in the miniperc
      group. CONCLUSION: Although SWL is the preferred treatment option for patients
      with medium-sized (10-20 mm) renal stones, endourologic methods also have been
      found to have a significant role. Relatively lower complication rates along with
      higher stone-free status observed with the RIRS technique compared with
      percutaneous approaches have made this method a valuable option in the management
      of such stones in recent years.

PMID- 25578511
TI  - Use of Pooled State Administrative Data for Mental Health Services Research.
AB  - State systems are a rich, albeit challenging, laboratory for policy-relevant
      services research studies. State mental health authorities routinely devote
      resources to collect data for state planning and reporting purposes. However,
      these data are rarely used in cross-state comparisons to inform state or federal
      policy development. In 2008, in response to key recommendations from the National
      Institute of Mental Health (NIMH) Advisory Council's "The Road Ahead: Research
      Partnership to Transform Services," (http://www.nimh.nih.gov/about/advisory
      boards-and-groups/namhc/reports/road-ahead.pdf), NIMH issued a request for
      applications (RFA) to support studies on the impact of state policy changes on
      access, cost, quality and outcomes of care for individuals with mental disorders.
      The purpose of the RFA was to bridge the divide between research and policy by
      encouraging research that used state administrative data across states, and to
      address significant state-defined health policy initiatives. Five projects
      involving eight states were selected through peer review for funding. Projects
      began in 2009 and were funded for 3 years. This report provides a brief
      description of the five projects, followed by an analysis of the impact,
      challenges, and lessons learned from these policy-partnered studies. We conclude
      by offering suggestions on ways to use state administrative data for informing
      state health policies, which is especially timely given national and state
      changes in the structure and financing of healthcare.

PMID- 25578512
TI  - Characterizing the Use of Research-Community Partnerships in Studies of Evidence
      Based Interventions in Children's Community Services.
AB  - This study characterized the use of research community partnerships (RCPs) to
      tailor evidence-based intervention, training, and implementation models for
      delivery across different childhood problems and service contexts using a survey
      completed by project principal investigators and community partners. To build on
      previous RCP research and to explicate the tacit knowledge gained through
      collaborative efforts, the following were examined: (1) characteristics of
      studies using RCP models; (2) RCP functioning, processes, and products; (3)
      processes of tailoring evidence-based practices for community implementation; and
      (4) perceptions of the benefits and challenges of collaborating with community
      providers and consumers. Results indicated that researchers were solely or
      jointly involved in the formation of almost all of the RCPs; interpersonal and
      operational processes were perceived as primary challenges; community partners'
      roles included greater involvement in implementation and participant recruitment
      than more traditional research activities; and the partnership process was
      perceived to increase the relevance and "fit" of interventions and research. 

PMID- 25578513
TI  - Assessing the progress of Mycobacterium tuberculosis H37Rv structural genomics.
AB  - Tuberculosis threatens human health nowhere more than in developing countries
      with large malnourished and/or immune-compromised (e.g. HIV infected)
      populations. The etiological agent, Mycobacterium tuberculosis (Mtb), is highly
      infectious and current interventions demonstrate limited ability to control the
      epidemic in particular of drug resistant Mtb strains. New drugs and vaccines are
      thus urgently required. Structural biologists are critical to the TB research
      community. By identifying potential drug targets and solving their three
      dimensional structures they open new avenues of identifying potential inhibitors
      complementing the screening of novel compounds and the investigation of Mtb's
      molecular physiology by pharmaceutical companies and academic researchers. Much
      effort has gone into structurally elucidating the Mtb proteome though much
      remains to be done with progress primarily limited by technological constraints.
      We review the currently available data for Mtb H37Rv to extract the lessons they
      have taught us. 

PMID- 25578514
TI  - Acute exercise preferentially redeploys NK-cells with a highly-differentiated
      phenotype and augments cytotoxicity against lymphoma and multiple myeloma target
      cells. Part II: impact of latent cytomegalovirus infection and catecholamine
      sensitivity.
AB  - We showed previously that acute exercise is associated with a preferential
      redeployment of highly-differentiated NK-cells and increased cytotoxicity against
      HLA-expressing tumor cell lines during exercise recovery. In this part II study,
      we retrospectively analyzed these findings in the context of latent
      cytomegalovirus (CMV) infection and performed additional experiments to explore
      potential mechanisms underpinning the marked reduction in NK-cell redeployment
      with exercise in CMV-seropositive individuals. We show here that latent CMV
      infection impairs NK-cell mobilization with exercise, only when the intensity of
      the exercise bout exceeds the individual blood lactate threshold (BLT). This
      impaired mobilization is associated with increased proportions of poorly exercise
      responsive NK-cell subsets (NKG2C+/KIR-, NKG2C+/NKG2A-, and NKG2C+/CD57+) and
      decreased NK-cell beta(2)-adrenergic receptor (AR) expression in those with CMV.
      As a result, NK-cell production of cyclic AMP (cAMP) in response to in vitro
      isoproterenol (synthetic beta-agonist) stimulation was drastically lower in those
      with CMV (6.0 vs. 20.3pmol/mL, p<0.001) and correlated highly with the proportion
      of NKG2C+/CD57+ NK-cells (R(2)=0.97). Moreover, NK-cell cytotoxic activity (NKCA)
      against the K562 (36.6% vs. 22.7%, p<0.05), U266 (23.6% vs. 15.9%, p<0.05), and
      221.AEH (41.3% vs. 13.3%, p<0.001) cell lines was increased at baseline in those
      infected with CMV; however, latent CMV infection abated the post-exercise
      increase in NKCA as a result of decreased NK-cell mobilization. Additionally,
      NKCA per cell against the U266 (0.24 vs. 0.12, p<0.01), RPMI-8226 (0.17 vs. 0.11,
      p<0.05), and 221.AEH (0.18 vs. 0.11, p<0.05) cell lines was increased 1h post
      exercise (relative to baseline) in CMV-seronegative subjects, but not in those
      infected with CMV. Collectively, these data indicate that latent CMV infection
      may compromise NK-cell mediated immunosurveillance after acute exercise due to an
      increased proportion of "CMV-specific" NK-cell subsets with impaired beta
      adrenergic receptor signaling pathways. 

PMID- 25578518
TI  - Spatiotemporal expression of Math6 during mouse embryonic development.
AB  - The basic helix-loop-helix transcription factor Math6 was shown to have important
      regulatory functions during many developmental events. However, a systematic
      description of Math6 expression during mouse embryonic development is up to now
      still lacking. We carried out this study to show Math6 expression at different
      stages of mouse embryonic development aiming to provide a wide insight into the
      regulatory functions during the mouse organogenesis. Using immunohistochemistry,
      we could show that Math6 expression is activated in the inner cell mass at the
      blastocyst stage and in the neural tube as well as somatic and splanchnic
      mesoderm at stage E8.5. At stages E8.5 and E10.5, Math6 transcripts were detected
      in the myotome, neural tube, pharyngeal arches, foregut and heart. At stages
      E11.5 and E12.5, Math6 transcripts were accumulated in the developing brain,
      heart, limb buds and liver. The heterozygous transgenic mouse embryos carrying
      EGFP-Cre under the Math6 promoter were used to analyze Math6 expression at later
      stages by means of immunohistochemistry against EGFP protein. EGFP was observed
      in the neural tube, heart, lung, skeletal muscle, skin, cartilage, trachea and
      aorta. We have observed Math6 expression in various organs at early and late
      stages of mouse development, which illustrates the involvement of Math6 in
      multiple developmental events.

PMID- 25578520
TI  - Twenty-five years of type I interferon-based treatment: a critical analysis of
      its therapeutic use.
AB  - The clinical exploitation of type I interferon (IFN) as an antiviral and
      antineoplastic agent is based on the properties originally attributed to this
      cytokine family, with schedules reflecting only their antiviral and
      antiproliferative activities. Nevertheless, type I IFN has emerged as a central
      activator of the innate immunity. As current schedules of treatment for chronic
      hepatitis C and for hematological and solid tumors, based on the continuous
      administration of recombinant type I IFN or pegylated formulations, disregard
      viral resistance, host genetic variants predicting treatment outcome and
      mechanisms of refractoriness, new administration schedules, the combination of
      type I IFN with new drugs and the increased monitoring of patients'
      susceptibility to type I IFN are expected to provide a new life to this valuable
      cytokine. 

PMID- 25578521
TI  - Interferon fundamentals: a tribute to the scientific vision of G B Rossi.
      Editorial.

PMID- 25578522
TI  - Defensins: "Simple" antimicrobial peptides or broad-spectrum molecules?
AB  - Small cationic peptides highly conserved in vertebrates, both alpha- and beta
      defensins were primarily identified as anti-microbial compounds involved in
      innate immunity. While human alpha-defensins are mostly expressed by neutrophils,
      beta-defensins are secreted by epithelial cells of the skin and mucosae. Besides
      their anti-microbial activity, accumulating data emerged in the past decade
      indicating that defensins have extended functions in human physio(patho)logy.
      Indeed, defensins appeared as modulators of the adaptive immune system and
      angiogenesis, key mediators of wound healing and determinant players in male
      fertility. Furthermore, the impact of defensin expression in cancer and the
      potential use of these small peptides as biomarkers or even therapeutic tools
      should not be ignored. In the present review, we describe recent research works
      regarding the diversified functions of defensins, by mainly focusing on human
      models. 

PMID- 25578519
TI  - Excitatory and inhibitory enteric innervation of horse lower esophageal
      sphincter.
AB  - The lower esophageal sphincter (LES) is a specialized, thickened muscle region
      with a high resting tone mediated by myogenic and neurogenic mechanisms. During
      swallowing or belching, the LES undergoes strong inhibitory innervation. In the
      horse, the LES seems to be organized as a "one-way" structure, enabling only the
      oral-anal progression of food. We characterized the esophageal and gastric
      pericardial inhibitory and excitatory intramural neurons immunoreactive (IR) for
      the enzymes neuronal nitric oxide synthase (nNOS) and choline acetyltransferase.
      Large percentages of myenteric plexus (MP) and submucosal (SMP) plexus nNOS-IR
      neurons were observed in the esophagus (72 +/- 9 and 69 +/- 8 %, respectively)
      and stomach (57 +/- 17 and 45 +/- 3 %, respectively). In the esophagus,
      cholinergic MP and SMP neurons were 29 +/- 14 and 65 +/- 24 vs. 36 +/- 8 and 38
      +/- 20 % in the stomach, respectively. The high percentage of nitrergic
      inhibitory motor neurons observed in the caudal esophagus reinforces the role of
      the enteric nervous system in the horse LES relaxation. These findings might
      allow an evaluation of whether selective groups of enteric neurons are involved
      in horse neurological disorders such as megaesophagus, equine dysautonomia, and
      white lethal foal syndrome.

PMID- 25578523
TI  - [Erratum for: Pre- and postoperative fast-track treatment concepts in spinal
      surgery . Patient information and patient cooperation].

PMID- 25578527
TI  - Pharmacological interaction between valproic acid and carbapenem: what about
      levels in pediatrics?
AB  - Valproic acid (VPA) is the most commonly used antiepileptic drug in pediatric
      patients, but its major drawback is its multiple pharmacological interactions.
      OBJECTIVE: To study children who had been simultaneously treated with carbapenems
      and valproic acid, considering drug levels, pharmacological interactions and
      clinical follow-up. MATERIAL AND METHODS: Retrospective study of children who
      simultaneously received treatment with VPA and carbapenems between January 2003
      and December 2011. Demographic variables, indication of treatment, dose, VPA
      plasma levels, interactions, clinical manifestations and medical management were
      analyzed. RESULTS: 28 children with concomitant treatment with both drugs were
      included in the study. 64.3% were males. 78.6% of the interactions were observed
      in the Intensive Care Unit. 60.7% of children had been previously treated VPA and
      its major indication were generalized seizures. Basal plasma levels of VPA were
      recorded in 53% and at 24 h after admittance in 60%. "40% of basal VPA levels
      were below therapeutic range prior to the administration of carbapenem. After the
      introduction of carbapenem 88% of level determinations were below therapeutic
      range". 54.5% of the patients that were chronically receiving VPA and had good
      control of epilepsy before admission had seizures during the coadministration.
      One patient that was on VPA before admission but with bad control of epilepsy
      worsened, and one patient that acutely received VPA did not achieve seizure
      freedom. In these cases it was necessary to either increase VPA dose or change to
      a different antiepileptic drug. CONCLUSIONS: Little is known about the mechanism
      of pharmacologic interactions between carbapenems and VPA, but it leads to a
      reduction in plasma levels that may cause a loss of seizure control, so
      simultaneous use of both drugs should be avoided when possible. If not, VPA
      levels should be monitored.

PMID- 25578528
TI  - The relationship between allergen immunotherapy and omalizumab for treating
      asthma.
AB  - Allergen-specific immunotherapy (AIT) is considered the only treatment capable of
      modifying the natural history of allergic respiratory disorders. The possible
      adverse events related to AIT have, until now, limited its use to mild and
      controlled asthma. The pre-administration or concomitant treatment of AIT and
      omalizumab (an anti-IgE humanized antibody), recommended for the treatment of
      severe allergic asthma, could be useful in reducing the adverse events due to AIT
      and to allow its use in patients with more severe or uncontrolled asthma.
      AIT/omalizumab combination has been explored in a few trials on asthma patients
      and also in other allergic disorders, such as rhinitis, hymenoptera systemic
      reaction and food allergy with significant results. We are at the beginning a new
      era where phenotype/endotype-based treatment will be associated with drug mass
      therapy and/or nonpharmacological phenotype/endotype-driven treatment to optimize
      disease control and/or to make the use of other treatments safer. 

PMID- 25578529
TI  - Increasing expression of substance P and calcitonin gene-related peptide in
      synovial tissue and fluid contribute to the progress of arthritis in
      developmental dysplasia of the hip.
AB  - INTRODUCTION: Developmental dysplasia of the hip (DDH) is a common
      musculoskeletal disorder that has pain and loss of joint function as major
      pathological features. In the present study, we explored the mechanisms of
      possible involvement and regulation of substance P (SP) and calcitonin gene
      related peptide (CGRP) in the pathological and inflammatory processes of
      arthritis in DDH. METHODS: Blood, synovial tissue and fluid samples were
      collected from patients diagnosed with different severities of DDH and from
      patients with femoral neck fracture. Levels of SP, CGRP and inflammatory
      cytokines in synovium and synovial fluid (SF) in the different groups were
      evaluated by immunohistochemistry, real-time PCR and enzyme-linked immunosorbent
      assay (ELISA). Correlations between neuropeptides and inflammatory cytokines in
      SF were evaluated by partial correlation analysis. The proinflammatory effects of
      SP and CGRP on synoviocytes obtained from patients with moderate DDH were
      investigated in vitro by real-time PCR and ELISA. The mechanisms of those effects
      were evaluated by Western blot analysis and nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) DNA binding assay. RESULTS:
      Significantly increased levels of neuropeptides and inflammatory cytokines were
      observed in synovium and SF from patients in the severe DDH group compared with
      the moderate DDH and control groups. In moderate DDH samples, SP in SF correlated
      with tumor necrosis factor (TNF)-alpha, and CGRP in SF correlated with TNF-alpha
      and interleukin (IL)-10. In the severe DDH group, SP in SF correlated with
      interleukin (IL)-1beta, TNF-alpha and IL-10. CGRP in SF correlated with TNF
      alpha. Additionally, SP might have had obvious proinflammatory effects on
      synoviocytes through the activation of NF-kappaB. CONCLUSIONS: The upregulation
      of SP and CGRP in synovium and SF might participate in the inflammatory process
      of arthritis in DDH. The activation of the NF-kappaB pathway seems indispensable
      in the proinflammatory effect of SP on synoviocytes. This original discovery may
      indicate a potential clinical drug target and the development of innovative
      therapies for DDH.

PMID- 25578534
TI  - Genotoxicity and cytotoxicity of ZnO and Al2O3 nanoparticles.
AB  - OBJECTIVES: Metal oxide nanoparticles (ZnO-NPs and Al2O3-NPs) are used in many
      fields, including consumer products and biomedical applications. As a result,
      exposure to these NPs is highly frequent, however, no conclusive information on
      their potential cytotoxicity and genotoxicity mechanisms are available. For this
      reason, we studied cytotoxic and genotoxic effects of ZnO-NPs and Al2O3-NPs on
      human peripheral blood lymphocytes. MATERIALS AND METHODS: We obtained our goals
      by using MTT assay, Annexin V-FITC flow cytometry, and alkaline, neural and pH
      12.1 versions of comet assay. RESULTS: Exposure of lymphocytes to both NPs for 24
      h slightly decreased viability of lymphocytes at >= 0.5 mM. For the first time,
      we revealed using the comet assays that both ZnO-NPs and Al2O3-NPs caused a
      concentration-dependent increase of DNA single-strand breaks, but not alkali
      labile sites. Treatment with DNA glycosylases showed that the NPs induced
      oxidative DNA damage. DNA damage caused by both nanoparticles at 0.05 mM was
      removed within 120 min, however lymphocytes did not repair DNA damage induced by
      0.5 mM NPs. Studied nanoparticles did not induce apoptosis in lymphocytes.
      CONCLUSION: Our results suggest that ZnO-NPs and Al2O3-NPs at concentration up to
      0.5 mM did not exhibit cytotoxic effect but may exert genotoxic effect on
      lymphocytes, at least partially by the generation of oxidative DNA damage and
      strand breaks.

PMID- 25578535
TI  - The risk of birth defects after assisted reproduction.
AB  - PURPOSE: Aim of this study was to investigate the association between congenital
      malformations and type of conception (spontaneous or medically assisted).
      METHODS: This is a population based study using data from the regional data base
      of Lombardy, a Northern Italian Region with a population of about 10 million
      inhabitants. Included in the study were 277,043 neonates born in Lombardy during
      the study period 2010-2012. Adjusted and unadjusted odds ratios (OR), and
      corresponding 95% confidence intervals (CI), of congenital abnormalities were
      calculated using unconditional multiple logistic regression. RESULTS: A total of
      7057 births (2.5%) were reported after non spontaneous conception. Overall, the
      frequency of birth defects was 4.4% among births after spontaneous conception and
      6.7% among births after non spontaneous ones (OR = 1.67, 95%CI = 1.5-1.9). The
      association disappeared after taking into account the confounding effect of
      maternal age and factors associated with non spontaneous conception. The crude OR
      of abnormalities was higher than unity for any defect (OR = 1.67, 95%CI = 1.5
      1.9), multiple defects (OR = 1.76, 95%CI = 1.3-2.3), cardiovascular (OR = 2.05,
      95%CI = 1.8-2.4), musculoskeletal (OR = 2.05, 95%CI = 1.7-2.5) and metabolic
      system abnormalities (OR = 1.97, 95%CI = 1.1-3.5). Almost all these associations,
      however, disappeared after taking into account potential confounding with the
      exception of musculoskeletal defects (adjusted OR = 1.31, 95%CI = 1.1-1.6). In
      this case also, if adjustment for multiple comparison is taking into account,
      results did not reach statistical significance. CONCLUSIONS: The results of this
      analysis confirm the recently emerging view that the increased frequency of birth
      defects observed after ART/medically induced ovulation only is largely due to
      confounders.

PMID- 25578536
TI  - In vitro fertilization with preimplantation genetic screening improves
      implantation and live birth in women age 40 through 43.
AB  - PURPOSE: In Vitro Fertilization is an effective treatment for infertility;
      however, it has relatively low success in women of advanced maternal age (>37)
      who have a high risk of producing aneuploid embryos, resulting in implantation
      failure, a higher rate of miscarriage or birth of a child with chromosome
      abnormalities. The purpose of this study was to compare the implantation,
      miscarriage and live birth rates with and without preimplantation genetic
      screening (PGS) of embryos from patients aged 40 through 43 years. METHODS: This
      is a retrospective cohort study, comparing embryos screened for ploidy using
      trophectoderm biopsy and array comparative genomic hybridization to embryos that
      were not screened. We compared pregnancy outcomes for traditional fresh IVF
      cycles with day 5 embryo transfers, Frozen Embryo Transfer (FET) cycles without
      PGS and PGS-FET (FET of only euploid embryos) cycles of patients with maternal
      ages ranging from 40 to 43 years, undergoing oocyte retrievals during the period
      between 1/1/2011 and 12/31/2012. RESULTS: The implantation rate of euploid
      embryos transferred in FET cycles (50.9%) was significantly greater than for
      unscreened embryos transferred in either fresh (23.8%) or FET (25.4%) cycles. The
      incidence of live birth per transferred embryo for PGS-FET (45.5%) was
      significantly greater than for No PGS fresh (15.8%) or No PGS FET (19.0 %)
      cycles. The incidences of live birth per implanted sac for PGS FET cycles
      (89.3%), No PGS fresh cycles (66.7%) and No PGS FET cycles (75.0%) were not
      significantly different. CONCLUSIONS: The present data provides evidence of the
      benefits of PGS with regard to improved implantation and live birth rate per
      embryo transferred.

PMID- 25578538
TI  - Live birth following donor oocyte IVF/ICSI with surplus cryopreserved MicroTESE
      retrieved sperm: a case report.

PMID- 25578537
TI  - Expression pattern of glucose metabolism genes correlate with development rate of
      buffalo oocytes and embryos in vitro under low oxygen condition.
AB  - PURPOSE: This study evaluates the effect of low oxygen conditions (5 Vs 20%) on
      buffalo embryo development. Expression patterns of key glucose metabolism genes
      (HK, PFK, LDH, PDH, G6PDH and Glut1) were assessed in buffalo oocytes and embryos
      cultured at 5 and 20% oxygen and correlated with development rate. METHODS:
      Maturation rate was observed by determining MII stages by Aceto-orcein method and
      blastocyst formation was observed at 7 day post insemination (dpi). Expression
      levels of genes were determined by real time PCR in oocytes / embryos at 5 and
      20% O2. RESULTS: Oocyte maturation and blastocyst formation rates were
      significantly higher at 5% O2 as compared to 20% O2 (P < 0.05). The expression
      pattern of glycolytic genes (HK, PFK and G6PDH) indicated that oocytes and
      embryos under 5% O2 tend to follow anaerobic glycolysis and pentose phosphate
      pathways to support optimum embryo development. Under 20% O2, oocytes and embryos
      had high expression of PDH indicating higher oxidative phosphorylation. Further,
      less G6PDH expression at 20% O2 was indicative of lower pentose phosphate
      activity. Higher expression of LDH was observed in oocytes and embryos under 20%
      O2 indicating sub-optimal culture conditions. High Glut1 activity was observed in
      the oocytes / embryos at 5% O2, indicative of high glucose uptake correlating
      with high expression of glycolytic genes. CONCLUSION: The expression patterns of
      glucose metabolism genes could be a valuable indicator of the development
      potential of oocytes and embryos. The study indicates the importance of reduced
      oxygen conditions for production of good quality embryos.

PMID- 25578539
TI  - Lack of association between genetic polymorphisms in three folate-related enzyme
      genes and male infertility in the Chinese population.
AB  - PURPOSE: This study explored the possible association of four single nucleotide
      polymorphisms (SNPs) of the three folate-related enzyme genes: MTHFR C677T and
      A1298C, MTR A2756G and MTRR A66G, with male infertility in the Chinese
      population. METHODS: The polymorphic distributions of the four SNPs (MTHFR C677T
      and A1298C, MTR A2756G and MTRR A66G) were investigated by the method of SNaPshot
      in a Chinese cohort including 296 idiopathic infertile males with azoospermia or
      oligozoospermia and 204 fertile males. RESULTS: We found no evidence for an
      association between any of these variants (MTHFR C677T and A1298C, MTR A2756G and
      MTRR A66G) and male infertility. CONCLUSIONS: There is no evidence for an
      association between male infertility and polymorphism of the three folate-related
      enzyme genes in the Chinese population.

PMID- 25578541
TI  - Electrochemical red-ox therapy of prostate cancer in nude mice.
AB  - Minimally invasive therapies are increasingly in demand for organ-confined
      prostate tumors. Electrochemical therapy (EChT) is attractive, as it relies on
      locally-induced reduction-oxidation reactions to kill tumor cells. Its efficacy
      for prostate cancer was assessed in human PC-3 and LNCaP tumor xenografts growing
      subcutaneously in nude mice (n = 80) by applying 2 Stainless Steel vs. 4 Platinum
      Iridium (Pt-Ir) electrodes to deliver current densities of 10 to 35 mA/cm(2) for
      30 or 60 min. The procedure was uneventful in 90% of mice. No difference in tumor
      vs. body temperature was observed. Changes at electrode-tumor junctions were
      immediate, with dryness and acidity (pH2-3) at the anode and oedema and
      alkalinity (pH10-12) at the cathode. This was accompanied by cellular
      alterations, found more pronounced at the cathode. Such acidic and alkaline
      conditions were cytotoxic in vitro and dissolved cells at pH>10. In mice, tumor
      destruction was extensive by 24h with almost undetectable blood prostate specific
      antigen (LNCaP model) and covered the whole tumor surface by 4 days. EChT was
      most efficient at 25-30 mA/cm(2) for 60 min, yielding the longest recurrence-free
      survival and higher cure rates, especially with 4 Pt-Ir electrodes. EChT is a
      promising option to optimize for organ-confined prostate tumors.

PMID- 25578543
TI  - Analysis of B-cell subpopulations in monoclonal gammopathies.
AB  - BACKGROUND: Multiple myeloma (MM) is characterized by accumulation of
      pathological plasma cells (PCs) in bone marrow (BM) as a result of deregulation
      of B-cell development. To clarify its pathophysiology it is necessary to
      investigate in detail the developmental stages of B-cells. MATERIALS AND METHODS:
      Enumeration of total CD19-positive (CD19(+)) cells and their subpopulations
      together with PCs was done in peripheral blood (PB) and BM of newly diagnosed
      monoclonal gammopathy patients and control subjects. Representation of subsets
      was compared among groups and relationships between subset percentage and
      cytogenetic/biochemical findings were analyzed. RESULTS: A lower number of total
      CD19(+) cells was found in MM, particularly in advanced stages of disease.
      Reduction of naive (P < .01) and transitional B-cells (P < .05) and increase of
      switched memory and switched CD27(-) B-cells and germinal center founder cells
      were detected in PB of MM compared with controls (P < .01). Similar results were
      found in BM. beta2 microglobulin level in MM positively correlated with the
      number of PCs and negatively with percentage of naive B-cells (P < .05).
      CONCLUSION: Our results provided a detailed phenotypic profile and enumeration of
      B and PC subpopulations in monoclonal gammopathy patients. A reduced number of B
      cells and particularly a differentiation shift to more numerous antigen
      stimulated forms was observed in MM. This might indicate a potential source of
      myeloma-initiating cells in one of these subpopulations.

PMID- 25578544
TI  - Novelty of the arena impairs the cortisol-related increase in the aggression of
      matrinxa (Brycon amazonicus).
AB  - The dichotomic effect of a cortisol level rise in vertebrate behavior has been
      widely observed. Generally, a chronic increase of the hormone level inhibits
      aggression, while an acute rise increases aggression. However, in this study, we
      show that this increase in aggression through an acute rise of cortisol also
      depends on the context in which the agonistic interaction occurs in the tropical
      fish matrinxa, Brycon amazonicus. We combined two factors: the type of housing
      (resident or non-resident in the trial arena) and the level of cortisol at the
      beginning of the fight (normal level - control, or high level - hydrocortisone
      treated fish). The cortisol treatment increased the aggressiveness in the
      resident fish, but this effect was not observed in the non-resident fish, which
      fought in an unknown arena. The novelty of the arena may have elicited an
      "alerted state" in the non-resident fish; in this situation the fight was not the
      priority, and the cortisol effect in aggression could be impaired by a conflict
      between motivational systems (fear and aggression). In our knowledge, in fish,
      the increase of aggression promoted by an acute rise in cortisol levels was
      always tested and observed in a resident context, and the inhibition of cortisol
      effect in the agonist behavior is demonstrated for the first time. As the
      cortisol effect in aggression is observed in several taxa, the inhibition of
      aggressiveness increased by the novelty of the arena should be investigated in
      other groups to clarify the dynamics of this effect of cortisol in animal
      behavior. 

PMID- 25578545
TI  - [Immunological safety of transfusion].
AB  - Transfusion safety lies on the strict application of measures aimed: at avoiding
      the occurrence of acute hazards, as far as they can be prevented by e.g. the ABO
      compatibility for red blood cell concentrates and therapeutic plasma; at reducing
      the frequency of other acute accidents such as TRALI or post-transfusion GVH
      (based on the implementation of measures which prove to be largely efficacious
      though not completely); and at reducing delayed incidents and hazards. The
      implementation of such immunological safety measures also aim at favoring the
      transfusion efficacy, in avoiding the lysis of transfused red cells or platelets.
      Perfect immunological compatibility (match) is impossible because transfused
      cells expose several hundreds of molecular variants with antigenic properties.
      Adaptive immunity is largely based upon antigen/antibody conflicts and it
      predominates in transfusion immunological hazards, but inflammation (as well as
      other components of innate immunity) is now acknowledged as a major actor of
      transfusion immunological linked hazards. 

PMID- 25578546
TI  - [Prophylactic salpingectomy or salpingo-oophorectomy as an ovarian cancer
      prevention?].
AB  - A recent hypothesis has stated that many ovarian cancers (especially high-grade
      serous histotype) could arise from the distal part of the fallopian tube. On one
      hand we know that risk-reducing salpingo-oophorectomy is the most effective
      prevention for ovarian cancer among BRCA mutation carriers. On the other,
      oophorectomy increases the relative risk for cardiovascular, osteoporotic
      psychosexual and cognitive dysfunctions in premenopausal women. This raises the
      question whether bilateral salpingectomy could be an effective strategy in the
      prevention of ovarian cancer in case of hereditary predisposition and in the
      general population. Here we discuss origin of ovarian cancer in the light of the
      latest molecular studies and the relative risks and benefits of a strategy of
      exclusive salpingectomy in comparison with the classical adnexectomy. 

PMID- 25578547
TI  - [Hypersexuality in Parkinson's disease. Advantage of the presence of the
      entourage for medical assessment].
AB  - OBJECTIVE: To improve the management of hypersexuality caused by antiparkinsonian
      treatment and its psychopathological implications in patients with Parkinson's
      disease (PD). If hypersexuality is a classic form of impulse control disorder
      (ICD) observed in PD, its rate is certainly underestimated. METHODS: We have
      proposed to meet patients with Parkinson's disease, referred by the neurology
      department of Lille University Hospital, for detection or suspicion of
      hypersexuality, in the presence of their spouse. The session consisted of an
      interview conducted by our psychiatry team. This evaluation was conducted between
      January 1 and August 31, 2011. Nine patients were referred to our service, 7
      agreed to meet us, 6 of them with their spouse. RESULTS: An interview in the
      presence of the spouse has improved hypersexuality screening and information
      given to the patient and his close contacts regarding the side effects of
      treatment, and particularly the occurrence of hypersexuality. It also highlighted
      the various expressions of these behavioral changes, often minimized by patients,
      as spouses had great difficulty dealing with this. It helped them to improve
      verbal communication and, therefore, to be more informative concerning sexual
      behavior changes in connection with the treatment and its management. Finally, it
      has enabled improved support for secondary consequences of this impulse control
      disorder, such as guilt, jealousy or shame. Our interest has also focused on the
      impact of this hypersexuality on patients' families. Among the six sets partners,
      four had symptoms requiring specific psychiatric care: depression, suicidal
      intention or post-traumatic stress disorder. PERSPECTIVE: Hypersexuality seems
      underestimated in patients receiving antiparkinsonian treatment. This
      underestimation is probably linked to some defense mechanisms such as denial or
      minimization, but also to the feelings generated by these behavioral problems,
      such as shame or guilt. On the other hand, some patients do not experience stress
      related behavioral changes (even though the family may complain). Systematic
      partner interview could be a solution to improving this screening.

PMID- 25578548
TI  - Abdominal cocoon, an uncommon cause of intestinal obstruction.

PMID- 25578549
TI  - [Blood transfusion: the challenges for tomorrow?].
AB  - As any therapeutic means, blood transfusion requires regular evaluation,
      particularly for its indications, effectiveness and risks. The availability of
      randomized clinical trials, the evolution of the quality of blood components, and
      the economic constraints shared by all countries, all lead to rethink both
      transfusion therapy as a whole and the organization of the transfusion chain from
      donor to recipient. The main tools available to improve transfusion and the
      transfusion chain management are the following: programs of patient blood
      management (PBM) to optimize the use of blood products with a patient centred
      approach, blood supply management tools to improve the effectiveness and
      efficiency of the transfusion chain, donor management tools to adapt donor
      collections to the patients' needs in compliance with safety requirements for
      patients and donors, and coordination of these activities. A better understanding
      of these tools and their implementation will certainly be major challenges for
      transfusion medicine in the near future. Integrating these evolutions in
      regulations through the revision of the European Directives on blood and blood
      components (the review process is expected to be launched in 2015) should enroll
      them in the long term, for the benefit of patients, donors and all other
      stakeholders involved in the transfusion chain. 

PMID- 25578550
TI  - [Blood transfusion and supply chain management safety].
AB  - The level of safety attained in blood transfusion now makes this a discipline
      better managed care activities. This was achieved both by scientific advances and
      policy decisions regulating and supervising the activity, as well as by the
      quality system, which we recall that affects the entire organizational structure,
      responsibilities, procedures, processes and resources in place to achieve quality
      management. So, an effective quality system provides a framework within which
      activities are established, performed in a quality-focused way and continuously
      monitored to improve outcomes. This system quality has to irrigate all the actors
      of the transfusion, just as much the establishments of blood transfusion than the
      health establishments. 

PMID- 25578551
TI  - [An hemorrhagic fever with renal syndrome revealing a leptospirosis].

PMID- 25578552
TI  - [Blood transfusion - the value of Research and Development programs].
AB  - Transfusion is a mixed discipline which includes the production of blood
      components, applied biology aiming in particular at establishing the highest
      compatibility for immunological characteristics between blood components to be
      delivered to patients and recipients, and, finally translational medicine to
      evaluate the effectiveness of the transfused products and to proactively avoid
      hazards, at least those that are preventible and can be anticipated. The whole
      chain takes place with the concern of continuous improvement of quality and
      safety. These two principles (quality/safety) have been and still are concerns of
      constant progress applicable to all the transfusion chain steps; they benefit
      from programs of Research and Development (R&D). Fundamental research, basic but
      also applied and clinical research, accompanies, in a constantly joint manner,
      scientific and medical progresses by providing new solutions to dampen the
      current problems and to prepare the future. 

PMID- 25578553
TI  - [Rare cause of ileo-colic intessusception in adults].

PMID- 25578554
TI  - [The leech: an unusual respiratory emergency].

PMID- 25578555
TI  - Uniparental disomy as a cause of spinal muscular atrophy and progressive
      myoclonic epilepsy: phenotypic homogeneity due to the homozygous c.125C>T
      mutation in ASAH1.
AB  - Spinal muscular atrophy and progressive myoclonic epilepsy (SMAPME, OMIM#159950)
      is a rare autosomal recessive disorder characterized by the combination of
      progressive myoclonic epilepsy and muscular weakness due to lower motor neuron
      disease. Mutations in ASAH1, previously associated only to Farber disease, have
      been recently described in seven patients with SMAPME. A homozygous c.125C>T
      mutation was initially found in six patients with a clinical homogeneous
      phenotype. A heterozygous compound mutation found in an additional patient has
      broadened the clinical and genetic spectrum of clinical SMAPME. We report a new
      case of a 13-year-old girl with SMAPME with the homozygous ASAH1 c.125C>T
      mutation, unique in that it is due to paternal uniparental disomy. She
      experienced muscle weakness from the age of three due to lower motor neuron
      involvement that lead to severe handicap and onset in late childhood of a
      progressive myoclonic epilepsy. This clinical picture fully overlaps with that of
      previously reported patients with this mutation and supports our view that the
      clinical phenotype associated with the homozygous c.125C>T mutation constitutes a
      clinically homogenous and recognizable disease. 

PMID- 25578557
TI  - The increasing value of plant-made proteins.
AB  - The production of high-value proteins in plants is maturing, as shown by the
      recent approval of innovative products and the latest studies that showcase plant
      based production systems using technologies and approaches that are well
      established in other fields. These include host cell engineering, medium
      optimization, scalable unit operations for downstream processing (DSP),
      bioprocess optimization and detailed cost analysis. Product-specific benefits of
      plant-based systems have also been exploited, including bioencapsulation and the
      mucosal delivery of minimally processed topical and oral products with a lower
      entry barrier than pharmaceuticals for injection. Success stories spearheaded by
      the FDA approval of Elelyso developed by Protalix have revitalized the field and
      further interest has been fueled by the production of experimental Ebola
      treatments in plants. 

PMID- 25578556
TI  - Method for quantitative analysis of nonsense-mediated mRNA decay at the single
      cell level.
AB  - Nonsense-mediated mRNA decay (NMD) is a ubiquitous mechanism of degradation of
      transcripts with a premature termination codon. NMD eliminates aberrant mRNA
      species derived from sources of genetic variation such as gene mutations,
      alternative splicing and DNA rearrangements in immune cells. In addition, recent
      data suggest that NMD is an important mechanism of global gene expression
      regulation. Here, we describe new reporters to quantify NMD activity at the
      single cell level using fluorescent proteins of two colors: green TagGFP2 and far
      red Katushka. TagGFP2 was encoded by mRNA targeted to either the splicing
      dependent or the long 3'UTR-dependent NMD pathway. Katushka was used as an
      expression level control. Comparison of the fluorescence intensities of cells
      expressing these reporters and cells expressing TagGFP2 and Katushka from
      corresponding control NMD-independent vectors allowed for the assessment of NMD
      activity at the single cell level using fluorescence microscopy and flow
      cytometry. The proposed reporter system was successfully tested in several
      mammalian cell lines and in transgenic Xenopus embryos. 

PMID- 25578558
TI  - Nanometer-sized dynamic entities in an aqueous system.
AB  - Using neutron spin-echo and backscattering spectroscopy, we have found that at
      low temperatures water molecules in an aqueous solution engage in center-of-mass
      dynamics that are different from both the main structural relaxations and the
      well-known localized motions in the transient cages of the nearest neighbor
      molecules. While the latter localized motions are known to take place on the
      picosecond time scale and Angstrom length scale, the slower motions that we have
      observed are found on the nanosecond time scale and nanometer length scale. They
      are associated with the slow secondary relaxations, or excess wing dynamics, in
      glass-forming liquids. Our approach, therefore, can be applied to probe the
      characteristic length scale of the dynamic entities associated with slow dynamics
      in glass-forming liquids, which presently cannot be studied by other experimental
      techniques. 

PMID- 25578559
TI  - KLF10 affects pancreatic function via the SEI-1/p21Cip1 pathway.
AB  - TGF-beta plays a significant role in regulating pancreas islet function and
      maintaining their mass. KLF10, a TGF-beta downstream gene, belongs to a group of
      Kruppel-like transcription factors that bind to the promoters of target genes and
      produce effects that mimic TGF-beta as a tumor suppressor. Using ChIP-chip
      screening, SEI-1 was identified as a target gene that may be regulated by KLF10.
      We conducted a series of assays to verify the presence of unknown regulation
      events between SEI-1 and KLF10. These showed that KLF10 transcriptionally
      activates the SEI-1 promoter and, furthermore, induces SEI-1 protein expression
      in pancreatic carcinoma cells. SEI-1 is one of the key factors involved in cell
      cycle control through the regulation of other transcription factors such as the
      p21(Cip1) gene. Interestingly, it has been shown previously that p21(Cip1) is
      indirectly activated by KLF10. Our results first demonstrated that KLF10 acts as
      a transcriptional activator on SEI-1, which can then result in increased
      p21(Cip1) expression. Furthermore, KLF10-deficiency in mice is associated with a
      decrease in the pancreatic islet mass, which is similar to the effects found in
      SEI-1 deficient mice. The KLF10-defect was also associated with the nuclear
      accumulation of the p21(Cip1) in islet cells. Based on our molecular and
      histological findings, we conclude that KLF10 plays an important role in
      pancreatic beta-cells and this supports a functional link between KLF10 and
      various cell cycle regulators, most notably in the context of the pancreas. 

PMID- 25578560
TI  - The conceptus regulates tryptophanyl-tRNA synthetase and superoxide dismutase 2
      in the sheep caruncular endometrium during early pregnancy.
AB  - Conceptus-derived paracrine signals play crucial roles in the preparation of a
      uterine environment capable of supporting implantation and development of the
      conceptus. However, little is known about the regulation of endometrial
      tryptophanyl tRNA synthetase (WARS) and manganese superoxide dismutase (SOD2)
      protein expression by the implanting and post-implanting conceptus. We
      hypothesized that the conceptus-derived signals favourably influences uterine
      environment for implantation through regulation of WARS and SOD2 expression in
      ovine caruncular endometrium. To test this hypothesis, WARS and SOD2 protein and
      mRNA expression was determined in caruncular endometrial tissues of unilaterally
      pregnant ewes at implantation (day 16) and post-implantation (day 20) periods.
      WARS protein expression increased in caruncular tissues of the gravid uterine
      horns compared with the non-gravid uterine horns on days 16 and 20 of pregnancy.
      There were no changes in SOD2 protein expression between the gravid and non
      gravid uterine horns, irrespective of the day of pregnancy. On day 16 of
      pregnancy, there were no differences in WARS and SOD2 mRNA expression between the
      gravid and non-gravid uterine horns but expression of both genes was higher in
      the gravid uterine horns when compared with the non-gravid uterine horns on day
      20 of pregnancy. In conclusion, the use of the unilaterally pregnant ewe model
      provides for the first time firm evidence that the early implantation and post
      implanting conceptus-derived signals up-regulate WARS protein expression within
      the caruncular endometrium. Further studies are necessary to identify these
      signalling molecules and to understand mechanisms whereby they exert paracrine
      action within the endometrium. 

PMID- 25578561
TI  - SOD2 is a C-myc target gene that promotes the migration and invasion of tongue
      squamous cell carcinoma involving cancer stem-like cells.
AB  - Our previous studies revealed that manganese superoxide dismutase (SOD2)
      contributes to the migration and invasion of tongue squamous cell carcinoma
      (TSCC). The purpose of the current study was to further clarify the mechanisms of
      SOD2 in the migration and invasion of TSCC. Side population (SP) cells were used
      as cancer stem-like cells and further assessed by sphere and colony formation
      assays, and the expression of stem cell markers (Bmi1, Nanog and ABCG2). We found
      that UM1 cells (TSCC cells with increased SOD2 expression, migration and invasion
      abilities) possessed a higher proportion of SP cells, sphere and colony
      formation, and expressed a higher level of stem cell markers compared to UM2
      cells (reduced SOD2 expression, migration and invasion abilities). SOD2
      expression as well as migration and invasion abilities were enhanced in SP cells
      compared to non-SP cells. Knockdown of SOD2 in UM1 cells or SP cells inhibited
      the migration and invasion abilities, reduced sphere and colony formation, and
      the expression of stem cell markers. Direct binding of the C-myc protein to the
      SOD2 promoter was demonstrated by chromatin immunoprecipitation and luciferase
      assays. Knockdown of C-myc in UM1 cells inhibited SOD2 expression as well as
      migration and invasion abilities. Our results indicate that cancer stem-like
      cells play an important role in the migration and invasion of TSCC. SOD2 is a
      direct target gene of C-myc and C-myc-SOD2-mediated migration and invasion of
      TSCC involve cancer stem-like cells. 

PMID- 25578562
TI  - Sonodynamic therapy induces the interplay between apoptosis and autophagy in K562
      cells through ROS.
AB  - Sonodynamic therapy (SDT) is a relatively new approach in the treatment of
      various cancers including leukemia cells. The aim of this study is to investigate
      the occurrence of apoptosis and autophagy after treated by protoporphyrin IX
      (PpIX)-mediated SDT (PpIX-SDT) on human leukemia K562 cells as well as the
      relationship between them. Firstly, mitochondrial-dependent apoptosis was
      observed through morphological observation and biochemical analysis. Meanwhile,
      SDT was shown to induce autophagy in K562 cells, which caused an increase in EGFP
      LC3 puncta cells, a conversion of LC3 II/I, formation of acidic vesicular
      organelles (AVOs) and co-localization between LC3 and LAMP2 (a lysosome marker).
      Besides, pretreatment with autophagy inhibitor 3-MA or bafilomycin A1 was shown
      to provide protection against autophagy and to enhance SDT-induced apoptosis and
      necrosis, while the apoptosis suppressor z-VAD-fmk failed to affect formation of
      autophagic vacuoles or partially prevented SDT-induced cytotoxicity, which
      suggested that SDT-induced autophagy functioned as a survival mechanism.
      Additionally, this study reported apparent apoptosis and autophagy with
      dependence on intracellular reactive oxygen species (ROS) production. Preliminary
      data showed that ROS scavenger N-acetylcysteine (NAC) effectively blocked the SDT
      induced accumulation of ROS, reversed sono-damage, cell apoptosis and autophagy.
      Taken together, these data indicate that autophagy may be cytoprotective in our
      experimental system, and the ROS caused by PpIX-SDT treatment may play an
      important role in initiating apoptosis and autophagy. 

PMID- 25578563
TI  - PKD1 is downregulated in non-small cell lung cancer and mediates the feedback
      inhibition of mTORC1-S6K1 axis in response to phorbol ester.
AB  - Protein kinase D1 (PKD1) is increasingly implicated in multiple biological and
      molecular events that regulate the proliferation or invasiveness in several
      cancers. However, little is known about the expression and functions of PKD1 in
      non-small cell lung cancer (NSCLC). In the present study, 34 pairs of human NSCLC
      and matched normal bronchiolar epitheliums were enrolled and evaluated for PKD1
      expression by quantitative real-time PCR. We showed that PKD1 was downregulated
      in 26 of 34 cancer tissues in comparison with matched normal epitheliums.
      Moreover, patients with venous invasion or lymph node metastasis showed
      significant lower expression of PKD1. Exposure of NSCLC A549 and H520 cells to
      the PKD family inhibitor kb NB 142-70(Kb), at concentrations that inhibited PKD1
      activation, strikingly potentiated S6K1 phosphorylation at Thr(389) and S6
      phosphorylation at Ser(235/236) in response to phorbol ester (PMA). Knockdown of
      PKD1 with siRNAs strikingly enhanced S6K1 phosphorylation whereas constitutively
      active PKD1 resulted in the S6K1 activity inhibition. Furthermore, the PI3K
      inhibitors LY294002, BKM120 and MEK inhibitors U0126, PD0325901 blocked the
      enhanced S6K1 activity induced by Kb. Collectively, our results identify
      decreased expression of the PKD1 as a marker for NSCLC and the loss of PKD1
      expression increases the malignant potential of NSCLC cells. This may be due to
      the function of PKD1 as a negative regulator of mTORC1-S6K1. Our results suggest
      that re-expression or activation of PKD1 might serve as a potential therapeutic
      target for NSCLC treatment. 

PMID- 25578564
TI  - New evidence in endometriosis.
AB  - Endometriosis is a recurrent and benign gynecological disorder characterized by
      the presence of endometrial tissue outside the cavity of the uterus. It is one of
      the most common diseases in the gynecological field, affecting about 10% of the
      female population in reproductive age. Despite this, its pathogenesis is still
      unacknowledged, there is a lack of early diagnostic markers and current therapies
      are only symptomatic. Considering the relevant health problems caused by
      endometriosis, all new information on this disease may have important clinical
      implications. The aim of this article is to summarize the latest advances in the
      pathogenesis, diagnosis and therapy of endometriosis that have recently been
      proposed by our research group. The possible clinical implications of these
      findings will be discussed. 

PMID- 25578566
TI  - Implications of metabotropic glutamate receptor structures for drug discovery in
      neurotherapeutics.
AB  - Recent technological advances in the field of membrane protein structural biology
      have led to significantly improved success rates in the structure resolution of G
      protein-coupled receptors. Apart from gaining insight into the mechanics of
      receptor biology, these technical advances facilitate the application of
      structure-based drug discovery to G protein-coupled receptors. Structure-based
      drug discovery has the potential to significantly increase the efficiency and
      success rate of drug discovery campaigns against this important family of drug
      targets. Recently, structures of mGlu1 and mGlu5 transmembrane domains were
      reported in complex with negative allosteric modulators. Analysis of these
      structures reveals a fascinating insight into the historical difficulties
      associated with the drug discovery efforts for these receptors and provides an
      important novel template for structure-based drug discovery approaches to
      identify more diverse and better quality chemotypes. 

PMID- 25578580
TI  - Theoretical analysis, design and development of a 27-MHz folded loop antenna as a
      potential applicator in hyperthermia treatment.
AB  - PURPOSE: A hyperthermia system using a folded loop antenna applicator at 27 MHz
      for soft tissue treatment was investigated both theoretically and experimentally
      to evaluate its clinical value. MATERIALS AND METHODS: The electromagnetic
      analysis of a 27-MHz folded loop antenna for use in human tissue was based on a
      customised software tool and led to the design and development of the proposed
      hyperthermia system. The system was experimentally validated using specific
      absorption rate (SAR) distribution estimations through temperature distribution
      measurements of a muscle tissue phantom after electromagnetic exposure. Various
      scenarios for optimal antenna positioning were also performed. RESULTS:
      Comparison of the theoretical and experimental analysis results shows
      satisfactory agreement. The SAR level of 50% reaches 8 cm depth in the tissue
      phantom. Thus, based on the maximum observed SAR values that were of the order of
      100 W/kg, the antenna specified is suitable for deep tumour heating. CONCLUSIONS:
      Theoretical and experimental SAR distribution results as derived from this study
      are in agreement. The proposed folded loop antenna seems appropriate for use in
      hyperthermia treatment, achieving proper planning and local treatment of deeply
      seated affected areas and lesions.

PMID- 25578599
TI  - Fluorescent and colorimetric chemosensors for pyrophosphate.
AB  - Pyrophosphate anions play key roles in various biological and chemical processes.
      During the last few years, many exciting results have emerged regarding the
      development of fluorescent and colorimetric sensors for this biologically
      important species. In this review, we will cover the fluorescent and colorimetric
      chemosensors developed for the detection of pyrophosphate (PPi) since 2010. 

PMID- 25578596
TI  - Isotropic three-dimensional fast spin-echo Cube magnetic resonance
      dacryocystography: comparison with the three-dimensional fast-recovery fast spin
      echo technique.
AB  - INTRODUCTION: Three-dimensional fast spin-echo Cube (3D-FSE-Cube) uses modulated
      refocusing flip angles and autocalibrates two dimensional (2D)-accelerated
      parallel and nonlinear view ordering to produce high-quality volumetric image
      sets with high-spatial resolution. Furthermore, 3D-FSE-Cube with topical
      instillation of fluid can also be used for magnetic resonance dacryocystography
      (MRD) with good soft tissue contrast. The purpose of this study was to evaluate
      the technical quality and visualization of the lacrimal drainage system (LDS)
      when using the 3D-FSE-Cube sequence and the 3D fast-recovery fast spin-echo
      (FRFSE) sequence. METHODS: In total, 75 patients with primary LDS outflow
      impairment or postsurgical recurrent epiphora underwent 3D-FSE-Cube MRD and 3D
      FRFSE MRD at 3.0 T after topical administration of compound sodium chloride eye
      drops. Two radiologists graded the images from either of the two sequences in a
      blinded fashion, and appropriate statistical tests were used to assess
      differences in technical quality, visibility of ductal segments, and number of
      segments visualized per LDS. RESULTS: Obstructions were confirmed in 90 of the
      150 LDSs assessed. The technical quality of 3D-FSE-Cube MRD and 3D-FRFSE MRD was
      statistically equivalent (P = 0.871). However, compared with 3D-FRFSE MRD, 3D-FSE
      Cube MRD improved the overall visibility and the visibility of the upper drainage
      segments in normal and obstructed LDSs (P < 0.001). There was a corresponding
      increase in the number of segments visualized per LDS in both groups (P < 0.001).
      CONCLUSION: Compared with 3D-FRFSE MRD, 3D-FSE-Cube MRD potentially improves the
      visibility of the LDS.

PMID- 25578565
TI  - RBM5 and p53 expression after rat spinal cord injury: implications for neuronal
      apoptosis.
AB  - RBM5 (RNA-binding motif protein 5), a nuclear RNA binding protein, is known to
      trigger apoptosis and induce cell cycle arrest by regulating the activity of the
      tumor suppressor protein p53. However, its expression and function in spinal cord
      injury (SCI) are still unknown. To investigate whether RBM5 is involved in
      central nervous system injury and repair, we performed an acute SCI model in
      adult rats in this study. Our results showed RBM5 was unregulated significantly
      after SCI, which was accompanied with an increase in the levels of apoptotic
      proteins such as p53, Bax, and active caspase-3. Immunofluorescent labeling also
      showed that traumatic SCI induced RBM5 location changes and co-localization with
      active caspase-3 in neurons. To further probe the role of RBM5, a neuronal cell
      line PC12 was employed to establish an apoptotic model. Knockdown of RBM5
      apparently decreased the level of p53 as well as active caspase-3, demonstrating
      its pro-apoptotic role in neurons by regulating expressions of p53 and caspase-3.
      Taken together, our findings indicate that RBM5 promotes neuronal apoptosis
      through modulating p53 signaling pathway following SCI. 

PMID- 25578601
TI  - Direct activation of the proposed anti-diabetic receptor, GPR119 in
      cardiomyoblasts decreases markers of muscle metabolic activity.
AB  - GPR119 agonists are emerging rapidly as a pharmaceutical treatment of diabetes.
      Diabetes is a known risk factor for cardiovascular disease yet the cardiac
      specific consequences of GPR119 activation are unknown. This study demonstrated
      that GPR119 agonism in cardiac myoblasts reduces metabolic activity in high and
      low concentrations of fatty acids, with high concentrations of palmitate largely
      attenuating the effects of the GPR119 agonist, PSN632408. The effects of GPR119
      activation on gene and protein markers of metabolism were dependent on fatty acid
      exposure. Activating GPR119 did not affect cell hypertrophy of lipid accumulation
      regardless of lipid exposure. These results suggest that the pathways activated
      in response to GPR119 modulation in cardiac muscle cells differ between healthy
      and metabolically dysregulated states. However regardless of the pathway
      activated by GPR119, these effects may cause detrimental reductions to
      oxidative/metabolic capacity under both conditions. Thus further development of
      GPR119 agonists for treating metabolic diseases is warranted. 

PMID- 25578603
TI  - The role of TGF-beta/Smad signaling in dopamine agonist-resistant prolactinomas.
AB  - BACKGROUND: Prolactinomas are the most common secretory pituitary adenomas. The
      first line of treatment involves dopamine agonists (DAs); however, a subset of
      patients is resistant to such therapy. Recent studies suggest that dopamine can
      up-regulate TGF-beta1 synthesis in rat pituitary lactotrophs whereas estradiol
      down-regulates TGF-beta1. To date, the role of TGF-beta/Smad signaling in DAs
      resistant prolactinomas has not been explored. METHODS: High-content screening
      (HCS) techniques, qRT-PCR, Western blot, immunofluorescence and ELISA, were
      performed to determine the role of TGF-beta/Smad signaling in DAs-resistant
      prolactinomas. RESULTS: We reported a significant down-regulation of TGF
      beta/Smad signaling cascade in DAs-resistant prolactinomas compared to normal
      human anterior pituitaries. Following treatment with TGF-beta1, the dopamine
      agonist, bromocriptine, and the estrogen antagonist (ER), fulvestrant in GH3
      cells, we found that TGF-beta1 and fulvestrant caused significant cytotoxicity in
      a dose- and time-dependent manner and activated Smad3 was detected following
      exposure to TGF-beta1 and fulvestrant. In addition, treating GH3 cells with
      fulvestrant increased active TGF-beta1 levels and decreased PRL levels in a dose
      dependent manner. CONCLUSION: TGF-beta/Smad signaling pathway may play an
      important role in DA-resistant prolactinomas and has the potential to be a viable
      target for the diagnosis and treatment of prolactinomas, particularly in patients
      who are resistant to DAs.

PMID- 25578604
TI  - Epigenetic mechanisms of melatonin action in human SH-SY5Y neuroblastoma cells.
AB  - We have shown that melatonin induces histone hyperacetylation in vitro and in
      vivo. To clarify the mechanisms involved, we have now investigated its effects on
      histone acetylation and signaling pathways in human SH-SY5Y neuroblastoma cells,
      which express melatonin MT1 receptors. Melatonin caused significant concentration
      dependent increases in both histone H3 and H4 acetylation. Blockade of melatonin
      receptors with luzindole abolished the histone hyperacetylating effect of
      melatonin, whereas inhibition of MAPK-ERK by PD98059 attenuated but did not block
      this effect. Melatonin treatment for 24-h decreased the levels of phospho-ERK1/2,
      but significantly increased Akt phosphorylation and protein expression of the
      histone acetyltransferase, p300. These findings suggest that the epigenetic
      effects of melatonin in SH-SY5Y cells are mediated by G protein-coupled MT1
      melatonin receptors. Furthermore, upregulation of the histone
      acetyltransferase/transcriptional co-activator p300, along with phosphorylation
      of Akt, which is essential for p300 activation, appear to be key mechanisms
      underlying the epigenetic effects of melatonin. 

PMID- 25578600
TI  - The sexual dimorphism of obesity.
AB  - The NIH has recently highlighted the importance of sexual dimorphisms and has
      mandated inclusion of both sexes in clinical trials and basic research. In this
      review we highlight new and novel ways sex hormones influence body adiposity and
      the metabolic syndrome. Understanding how and why metabolic processes differ by
      sex will enable clinicians to target and personalize therapies based on gender.
      Adipose tissue function and deposition differ by sex. Females differ with respect
      to distribution of adipose tissues, males tend to accrue more visceral fat,
      leading to the classic android body shape which has been highly correlated to
      increased cardiovascular risk; whereas females accrue more fat in the
      subcutaneous depot prior to menopause, a feature which affords protection from
      the negative consequences associated with obesity and the metabolic syndrome.
      After menopause, fat deposition and accrual shift to favor the visceral depot.
      This shift is accompanied by a parallel increase in metabolic risk reminiscent to
      that seen in men. A full understanding of the physiology behind why, and by what
      mechanisms, adipose tissues accumulate in specific depots and how these depots
      differ metabolically by sex is important in efforts of prevention of obesity and
      chronic disease. Estrogens, directly or through activation of their receptors on
      adipocytes and in adipose tissues, facilitate adipose tissue deposition and
      function. Evidence suggests that estrogens augment the sympathetic tone
      differentially to the adipose tissue depots favoring lipid accumulation in the
      subcutaneous depot in women and visceral fat deposition in men. At the level of
      adipocyte function, estrogens and their receptors influence the expandability of
      fat cells enhancing the expandability in the subcutaneous depot and inhibiting it
      in the visceral depot. Sex hormones clearly influence adipose tissue function and
      deposition, determining how to capture and utilize their function in a time of
      caloric surfeit, requires more information. The key will be harnessing the
      beneficial effects of sex hormones in such a way as to provide 'healthy'
      adiposity. 

PMID- 25578602
TI  - Distribution and function of 3',5'-Cyclic-AMP phosphodiesterases in the human
      ovary.
AB  - The concentration of the important second messenger cAMP is regulated by
      phosphodiesterases (PDEs) and hence an attractive drug target. However, limited
      human data are available about the PDEs in the ovary. The aim of the present
      study was to describe and characterise the PDEs in the human ovary. Results were
      obtained by analysis of mRNA microarray data from follicles and granulosa cells
      (GCs), combined RT-PCR and enzymatic activity analysis in GCs,
      immunohistochemical analysis of ovarian sections and by studying the effect of
      PDE inhibitors on progesterone production from cultured GCs. We found that PDE3,
      PDE4, PDE7 and PDE8 are the major families present while PDE11A was not detected.
      PDE8B was differentially expressed during folliculogenesis. In cultured GCs,
      inhibition of PDE7 and PDE8 increased basal progesterone secretion while PDE4
      inhibition increased forskolin-stimulated progesterone secretion. In conclusion,
      we identified PDE3, PDE4, PDE7 and PDE8 as the major PDEs in the human ovary. 

PMID- 25578611
TI  - Metal uptake via phosphate fertilizer and city sewage in cereal and legume crops
      in Pakistan.
AB  - Crop irrigation with heavy metal-contaminated effluents is increasingly common
      worldwide and necessitates management strategies for safe crop production on
      contaminated soils. This field study examined the phytoavailability of three
      metals (Cd, Cu, and Zn) in two cereal (wheat, maize) and legume (chickpea,
      mungbean) crops in response to the application of either phosphatic fertilizer or
      sewage-derived water irrigation over two successive years. Five fertilizer
      treatments, i.e. control, recommended nitrogen (N) applied alone and in
      combination of three levels of phosphorus (P), half, full and 1.5 times of
      recommended P designated as N0P0, N1P0, N1P0.5, N1P1.0, and N1P1.5, respectively.
      Tissue concentrations of Cd, Cu, Zn, and P were determined in various plant
      parts, i.e., root, straw, and grains. On the calcareous soils studied while
      maximum biomass production was obtained with application of P at half the
      recommended dose, the concentrations of metals in the crops generally decreased
      with increasing P levels. Tissue metal concentrations increased with the
      application of N alone. Translocation and accumulation of Zn and Cu were
      consistently higher than Cd. And the pattern of Cd accumulation differed among
      plant species; more Cd being accumulated by dicots than monocots, especially in
      their grains. The order of Cd accumulation in grains was maize > chickpea >
      mungbean > wheat. Mungbean and chickpea straws also had higher tissue Cd
      concentration above permissible limits. The two legume species behaved similarly,
      while cereal species differed from each other in their Cd accumulation. Metal ion
      concentrations were markedly higher in roots followed by straw and grains.
      Increasing soil-applied P also increased the extractable metal and P
      concentrations in the post-harvest soil. Despite a considerable addition of
      metals by P fertilizer, all levels of applied P effectively decreased metal
      phytoavailability in sewage-irrigated soils, and applying half of the recommended
      dose of P fertilizer was the most feasible solution for curtailing plant metal
      uptake from soils. These findings may have wide applications for safer crop
      production of monocot species when irrigating crops with sewage effluent-derived
      waters.

PMID- 25578612
TI  - Combined chemical and toxicological evaluation of leachate from municipal solid
      waste landfill sites of Delhi, India.
AB  - In the present study, landfill leachate of three landfill sites of Delhi, India,
      was toxico-chemically analyzed for human risk assessment. Raw leachate samples
      were collected from the municipal solid waste (MSW) landfills of Delhi lacking
      liner systems. Samples were characterized with relatively low concentrations of
      heavy metals while the organic component exceeded the upper permissible limit by
      up to 158 times. Qualitative analysis showed the presence of numerous xenobiotics
      belonging to the group of halogenated aliphatic and aromatic compounds,
      polycyclic aromatic hydrocarbons (PAHs), phthalate esters, and other emerging
      contaminants. Quantitative analysis of PAHs showed that the benzo(a)pyrene-toxic
      equivalence quotient (BaP-TEQ) ranged from 41.22 to 285.557 ng L(-1). The human
      risk assessment methodology employed to evaluate the potential adverse effects of
      PAHs showed that the cancer risk level was lower than the designated acceptable
      risk of 10(-6). However, significant cytotoxic and genotoxic effects of leachates
      on HepG2 cell line was observed with MTT EC50 value ranging from 11.58 to 20.44 %
      and statistically significant DNA damage. Thus, although the leachates contained
      low concentrations of PAHs with proven carcinogenic potential, but the mixture of
      contaminants present in leachates are toxic enough to cause synergistic or
      additive cytotoxicity and genotoxicity and affect human health.

PMID- 25578613
TI  - Reaction of cyclopropenes with a trichloromethyl radical: unprecedented ring
      opening reaction of cyclopropanes with migration.
AB  - The direct addition reaction of chloroform to cyclopropenes under triethylborane
      mediated radical reaction conditions to provide trichloromethylcyclopropanes has
      been developed. In contrast, using dimethylzinc as a radical initiator led to the
      formation of unconjugated esters via a domino sequence involving the addition of
      the trichloromethyl radical, rearrangement and ring-opening reactions. 

PMID- 25578614
TI  - The effects of disruptions in ribosomal active sites and in intersubunit contacts
      on ribosomal degradation in Escherichia coli.
AB  - Although ribosomes are very stable under most conditions, ribosomal degradation
      does occur in diverse groups of organisms in response to specific stresses or
      environmental conditions. While non-functional ribosome decay (NRD) in yeast is
      well characterized, very little is known of the mechanisms that initiate
      ribosomal degradation in bacteria. Here we test ribosome degradation in growing
      Escherichia coli expressing mutant ribosomes. We found that mutations in the 16S
      rRNA decoding centre (G530U and A1492C) and 23S rRNA active site (A2451G) do not
      lead to ribosomal degradation. In contrast, 23S rRNA mutation U2585A causes
      degradation of both the large and small ribosomal subunits in E. coli. We further
      tested mutations in 23S rRNA, which disrupt ribosomal intersubunit bridges B2a
      and B3. Deletion of helix 69 of 23S rRNA and the point mutation A1912G in the
      same helix did not destabilize ribosomes, while expression of mutations A1919G in
      H69 and A1960G in H71 led to degradation of both mutant and wild-type ribosomes.
      Our results suggest an actively induced mechanism requiring de novo protein
      synthesis for ribosomal degradation in E. coli, which degrades both structurally
      inactive and active ribosomes. 

PMID- 25578615
TI  - Deliberate self-harming application of superglue in the nose: case report and
      literature review.
AB  - BACKGROUND: Accidental and non-accidental applications of superglue in the ear,
      nose and oral cavity have been reported previously. Surgical removal of glue from
      the nose is the current practice. CASE REPORT: This paper reports the case of an
      18-year-old female, who presented with complete bilateral nasal occlusion due to
      deliberate self-application of superglue in both nostrils to avoid nasogastric
      tube insertion. RESULTS: Removal of glue was accomplished with a combination of
      local anaesthetic cream and acetone-soaked cotton buds, which caused only minimal
      discomfort to the patient. All traces of glue disappeared within 10 days, without
      causing damage to the nasal mucosa, nasal blockage or pain. CONCLUSION: To the
      best of our knowledge, this is the first case report of deliberate self
      application of superglue in the nose. A successful non-surgical management option
      for the removal of glue from the nose is introduced.

PMID- 25578616
TI  - To the editor: is the serum level of reactive oxygen metabolites appropriate for
      evaluating short-term surgical stress of patients undergoing colectomy?
AB  - To demonstrate whether reactive oxygen and free radical measuring are appropriate
      to evaluate short-term surgical stress after laparoscopic colectomy. The subjects
      consisted of 22 cases (laparoscopic surgery, 16; and laparotomy, 6) that
      underwent surgery for colon cancer. The reactive oxygen metabolites (ROM) value
      in the blood were measured perioperatively. The average ROM values immediately
      prior to surgery, immediately following surgery, and 1 day following surgery were
      360.1, 316.0, and 346.7 U.CARR, respectively, meaning that ROM declined
      immediately following surgery compared with immediately prior to surgery (P <
      0.05), while a tendency was observed for these values to increase again 1 day
      following surgery. In the comparison of pain control 1 day following surgery, a
      significantly lower value was indicated in the epidural anesthesia group (n = 12)
      compared with the fentanyl intravenous injection group (n = 10). Moreover, no
      significant change was observed in the surgical stress level in a comparison of
      patient background items such as age, sex, and so forth, laparoscopic surgery,
      and laparotomy. The low-invasiveness of laparoscopic surgery was not indicated in
      the ROM value 1 day following surgery, probably because pain control offsets the
      level of surgical stress using this method. 

PMID- 25578619
TI  - Metabolite Profiling of the Response of Burdock Roots to Copper Stress.
AB  - Arctium lappa L. (Asteraceae), also known as burdock, has a long history of
      cultivation as a dietary vegetable worldwide. Stress in plants disrupts metabolic
      homeostasis and requires adjustment of metabolic pathways. Exposure to heavy
      metals is one of the most prevalent environmental stresses encountered by plants.
      In this study, metabolite profiling based on 1H NMR and GC-MS was used to obtain
      a holistic view of the response of burdock roots to copper stress. The principal
      component analysis model generated from the NMR data showed significant
      separation between groups. Copper-treated burdock roots were characterized by
      increased levels of phenols and decreased levels of primary metabolites. These
      results suggest that copper stress leads to activation of the phenylpropanoid
      pathway and growth inhibition. GC-MS analyses revealed increased levels of
      unsaturated fatty acids and decreased levels of sterols in the copper-treated
      group. Changes in metabolite concentrations were analyzed by UPLC/QTRAP-MS, and
      the significances were confirmed by two-way analysis of variance and Bonferroni's
      test. Interestingly, linoleic acid was increased about 2.7-fold, from 316 +/-
      64.5 to 855 +/- 111 ppm, in the group treated with copper for 6 days. This study
      demonstrates that metabolomic profiling is an effective analytical approach to
      understanding the metabolic pathway(s) associated with copper stress in burdock
      roots.

PMID- 25578618
TI  - Characterization of a bispecific FLT3 X CD3 antibody in an improved, recombinant
      format for the treatment of leukemia.
AB  - FLT3 is a receptor-tyrosine-kinase that is expressed on leukemic cells of the
      myeloid and lymphoid lineage rather specifically. We here report on the
      construction and selection of bispecific FLT3 X CD3 antibodies in a new
      recombinant format, termed Fabsc, that resembles the normal antibody structure
      more closely than the well-established bispecific single chain (bssc)-format. Our
      preferred antibody, which emerged from an initial selection procedure utilizing
      different FLT3- and CD3-antibodies, contains the FLT3-antibody 4G8 and the CD3
      antibody UCHT1. The 4G8 X UCHT1 Fabsc-antibody was found to be superior to a bssc
      antibody with identical specificities with respect to (i) affinity to the target
      antigen FLT3, (ii) production yield by transfected cells, and (iii) the
      diminished formation of aggregates. T-cell activation in the presence and absence
      of cultured leukemic cells and killing of these cells was comparable for both
      molecules. In addition, the 4G8 X UCHT1 Fabsc-antibody was found to induce T-cell
      activation and efficient killing of leukemic blasts in primary peripheral blood
      mononuclear cell (PBMC) cultures of acute myeloid leukemia (AML) patients. In
      these experiments, the bispecific molecule was clearly superior to an Fc
      optimized monospecific FLT3-antibody described previously, indicating that within
      PBMC of AML patients the recruitment of T cells is more effective than that of
      natural killer cells. 

PMID- 25578621
TI  - Review of the current management of upper urinary tract injuries by the EAU
      Trauma Guidelines Panel.
AB  - CONTEXT: The most recent European Association of Urology (EAU) guidelines on
      urological trauma were published in 2014. OBJECTIVE: To present a summary of the
      2014 version of the EAU guidelines on upper urinary tract injuries with the
      emphasis upon diagnosis and treatment. EVIDENCE ACQUISITION: The EAU trauma
      guidelines panel reviewed literature by a Medline search on upper urinary tract
      injuries; publication dates up to December 2013 were accepted. The focus was on
      newer publications and reviews, although older key references could be included.
      EVIDENCE SYNTHESIS: A full version of the guidelines is available in print and
      online. Blunt trauma is the main cause of renal injuries. The preferred
      diagnostic modality of renal trauma is computed tomography (CT) scan.
      Conservative management is the best approach in stable patients. Angiography and
      selective embolisation are the first-line treatments. Surgical exploration is
      primarily for the control of haemorrhage (which may necessitate nephrectomy) and
      renal salvage. Urinary extravasation is managed with endourologic or percutaneous
      techniques. Complications may require additional imaging or interventions. Follow
      up is focused on renal function and blood pressure. Penetrating trauma is the
      main cause of noniatrogenic ureteral injuries. The diagnosis is often made by CT
      scanning or at laparotomy, and the mainstay of treatment is open repair. The type
      of repair depends upon the severity and location of the injury. CONCLUSIONS:
      Renal injuries are best managed conservatively or with minimally invasive
      techniques. Preservation of renal units is feasible in most cases. This review,
      performed by the EAU trauma guidelines panel, summarises the current management
      of upper urinary tract injuries. PATIENT SUMMARY: Patients with trauma benefit
      from being accurately diagnosed and treated appropriately, according to the
      nature and severity of their injury.

PMID- 25578622
TI  - Surgical tips and tricks during urethroplasty for bulbar urethral strictures
      focusing on accurate localisation of the stricture: results from a tertiary
      centre.
AB  - BACKGROUND: There are several techniques for characterising and localising an
      anterior urethral stricture, such as preoperative retrograde urethrography,
      ultrasonography, and endoscopy. However, these techniques have some limitations.
      The final determinant is intraoperative assessment, as this yields the most
      information and defines what surgical procedure is undertaken. OBJECTIVE: We
      present our intraoperative approach for localising and operating on a urethral
      stricture, with assessment of outcomes. DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective review of urethral strictures operated was carried out. All
      patients had a bulbar or bulbomembranous urethroplasty. All patients were
      referred to a tertiary centre and operated on by two urethral reconstructive
      surgeons. SURGICAL PROCEDURE: Intraoperative identification of the stricture was
      performed by cystoscopy. The location of the stricture is demonstrated externally
      on the urethra by external transillumination of the urethra and comparison with
      the endoscopic picture. This is combined with accurate placement of a suture
      through the urethra, at the distal extremity of the stricture, verified precisely
      by endoscopy. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Clinical data were
      collected in a dedicated database. Intraoperative details and postoperative
      follow-up data for each patient were recorded and analysed. A descriptive data
      analysis was performed. RESULTS AND LIMITATIONS: A representative group of 35
      male patients who had surgery for bulbar stricture was randomly selected from
      January 2010 to December 2013. Mean follow-up was 13.8 mo (range 2-43 mo). Mean
      age was 46.5 yr (range 17-70 yr). Three patients had undergone previous
      urethroplasty and 26 patients had previous urethrotomy or dilatation. All
      patients had preoperative retrograde urethrography and most (85.7%) had
      endoscopic assessment. The majority of patients (48.6%) had a stricture length of
      >2-7 cm and 45.7% of patients required a buccal mucosa graft. There were no
      intraoperative complications. Postoperatively, two patients had a urinary tract
      infection. All patients were assessed postoperatively via flexible cystoscopy.
      Only one patient required subsequent optical urethrotomy for recurrence.
      CONCLUSIONS: Our intraoperative strategy for anterior urethral stricture
      assessment provides a clear stepwise approach, regardless of the type of
      urethroplasty eventually chosen (anastomotic disconnected or Heineke-Mikulicz) or
      augmentation (dorsal, ventral, or augmented roof strip). It is useful in all
      cases by allowing precise localisation of the incision in the urethra, whether
      the stricture is simple or complex. PATIENT SUMMARY: We studied the treatment of
      bulbar urethral strictures with different types of urethroplasty, using a
      specific technique to identify and characterise the length of the stricture. This
      technique is effective, precise, and applicable to all patients undergoing
      urethroplasty for bulbar urethral stricture.

PMID- 25578623
TI  - A comparative analysis of swallowing accelerometry and sounds during saliva
      swallows.
AB  - BACKGROUND: Accelerometry (the measurement of vibrations) and auscultation (the
      measurement of sounds) are both non-invasive techniques that have been explored
      for their potential to detect abnormalities in swallowing. The differences
      between these techniques and the information they capture about swallowing have
      not previously been explored in a direct comparison. METHODS: In this study, we
      investigated the differences between dual-axis swallowing accelerometry and
      swallowing sounds by recording data from adult participants and calculating a
      number of time and frequency domain features. During the experiment, 55
      participants (ages 18-65) were asked to complete five saliva swallows in a
      neutral head position. The resulting data was processed using previously designed
      techniques including wavelet denoising, spline filtering, and fuzzy means
      segmentation. The pre-processed signals were then used to calculate 9 time,
      frequency, and time-frequency domain features for each independent signal.
      Wilcoxon signed-rank and Wilcoxon rank-sum tests were utilized to compare feature
      values across transducers and patient demographics, respectively. RESULTS: In
      addition to finding a number of features that varied between male and female
      participants, our statistical analysis determined that the majority of our chosen
      features were statistically significantly different across the two sensor methods
      and that the dependence on within-subject factors varied with the transducer
      type. However, a regression analysis showed that age accounted for an
      insignificant amount of variation in our signals. CONCLUSIONS: We conclude that
      swallowing accelerometry and swallowing sounds provide different information
      about deglutition despite utilizing similar transduction methods. This
      contradicts past assumptions in the field and necessitates the development of
      separate analysis and processing techniques for swallowing sounds and vibrations.

PMID- 25578624
TI  - Hydrophobic modification of chitin whisker and its potential application in
      structuring oil.
AB  - A facile approach was developed to modify chitin whiskers by reacting them with
      bromohexadecane, and the potential application of modified whiskers in
      structuring oil was evaluated. The results of Fourier transform infrared spectra
      (FT-IR), wide-angle X-ray diffraction (XRD), elemental analysis, solid (13)C NMR,
      and differential scanning calorimeter (DSC) confirmed that the long alkyl chains
      were successfully introduced to the chitin whiskers and endowed them with
      improved hydrophobicity and thermal transition. By hot pressing the modified
      whiskers, the highly hydrophobic whisker sheets were constructed, showing high
      contact angles close to 150 degrees . The hydrophobic interaction between the
      long alkyl chains and chitin backbone induced the crystal alignment with micro
      nano structure, leading to the surface roughness and high hydrophobicity of the
      sheets. Furthermore, the modified whiskers could form a stable dispersion in
      sunflower oil, displaying a remarkable thickening effect. The viscosity of the
      oily suspension exhibited temperature dependence and shear-thinning behavior,
      suggesting great potentials to fabricate oleogel without adding any saturated
      fat. Furthermore, the intrinsic biocompatibility of alpha-chitin structure
      benefits its application in foodstuff, cosmetics, and medical fields. 

PMID- 25578626
TI  - Weight loss prior to lung transplantation is associated with improved survival.
AB  - BACKGROUND: Obesity is associated with increased mortality after lung
      transplantation and is a relative contraindication to transplant. It is unknown
      whether weight reduction prior to transplantation ameliorates this risk. Our
      objective was to determine whether weight loss prior to lung transplantation
      improves survival. METHODS: Our investigation was a two-center, retrospective
      cohort study of lung transplant recipients between January 1, 2000 and November
      5, 2010. Change in weight, demographics, transplant details, lung allocation
      score, length of intensive care and mechanical ventilator days and graft and
      patient survival were abstracted. Wilcoxon's signed-rank test and the Cox
      proportional hazard model were used for analysis where appropriate. RESULTS:
      Three hundred fifty-five patients (55% male, median age 59 years) satisfied
      inclusion and exclusion criteria. After adjusting for standard demographic and
      clinical measures, a 1-unit reduction in BMI pre-transplant was associated with a
      reduced risk of death with a hazard ratio 0.89 (95% confidence interval 0.82 to
      0.96; p = 0.004). This survival benefit persisted in the group with baseline BMI
      >= 25 kg/m(2) (overweight and obese) and hazard ratio 0.85 (95% CI 0.77 to 0.95;
      p = 0.003), but not in those with a BMI <= 24.9 kg/m(2). The 1-unit reduction in
      BMI was also associated with a 6.1% decrease in median mechanical ventilator days
      (p = 0.02) and a trend toward decreased intensive care unit length of stay (p =
      0.06). CONCLUSIONS: A reduction in BMI prior to lung transplantation was
      associated with a reduction in the risk of death and mechanical ventilator days.
      A greater reduction in BMI was associated with a greater survival benefit.

PMID- 25578627
TI  - Outcomes after percutaneous coronary artery revascularization procedures for
      cardiac allograft vasculopathy in pediatric heart transplant recipients: A multi
      institutional study.
AB  - BACKGROUND: Cardiac allograft vasculopathy is an important cause of long-term
      graft loss. In adults, percutaneous revascularization procedures (PRPs) have
      variable success with high restenosis rates and little impact on graft survival.
      Limited data exist in pediatric recipients of transplants. METHODS: Data from the
      Pediatric Heart Transplant Study (PHTS) were used to explore associations between
      PRPs and outcomes after heart transplant in patients listed <=18 years old who
      received a first heart transplant between 1993 and 2009. RESULTS:
      Revascularization procedures were done in 28 of 3,156 (0.9%) patients; 13
      patients had multiple PRPs giving a total of 51 PRPs performed across 15 centers.
      Mean recipient age at time of transplant was 7.7 +/- 6.7 years; mean donor age
      was 15.9 +/- 15.4 years. The mean time to first PRP was 5.7 +/- 3.2 years.
      Vessels involved were left anterior descending artery (41%), right coronary
      artery (25%), circumflex artery (18%), other coronary branches/unknown (16%).
      PRPs consisted of 38 (75%) stent implantations and 13 (25%) balloon angioplasties
      with an overall procedural success rate of 73%. Freedom from graft loss after
      PRPs was 89%, 75%, and 61% at 1, 3, and 12 months. In addition, patients with
      transplants from donors >30 years old were found to have less freedom from the
      need for a revascularization procedure than patients with transplants from
      younger donors (p < 0.0001). CONCLUSIONS: In this large pediatric heart
      transplant cohort, use of PRPs for cardiac allograft vasculopathy was rare,
      likely related to procedural feasibility of the interventions. Despite
      technically successful interventions, graft loss occurred in 39% within 1 year
      post-procedure; relisting for heart transplant should be considered.

PMID- 25578625
TI  - Change in health-related quality of life from before to after destination therapy
      mechanical circulatory support is similar for older and younger patients:
      analyses from INTERMACS.
AB  - BACKGROUND: Destination therapy left ventricular assist devices (DT LVADs) are
      being implanted in older adults on an increasing basis. Older patients have a
      higher risk for mortality and morbidity post-LVAD, which may impact their health
      related quality of life (HRQOL). We aimed to determine the change in HRQOL by age
      from before implant to 1 year after DT LVAD implant and identify factors
      associated with the change. METHODS: Data were collected from 1,470 continuous
      flow DT LVAD patients at 108 institutions participating in INTERMACS from January
      21, 2010 to March 31, 2012. Patients were divided into three cohorts: <60 years
      of age (n = 457); 60 to 69 years of age (n = 520); and >=70 years of age (n =
      493). HRQOL was measured using the generic EuroQol instrument (EQ-5D-3L). Data
      were collected pre-implant and 3, 6 and 12 months post-implant. Statistical
      analyses included descriptive statistics, Kaplan-Meier survival analyses and
      multivariable regression analyses. RESULTS: HRQOL improved in all patients.
      Generally, older patients reported better HRQOL than younger patients pre-implant
      (>=70 years: mean 40; 60 to 69 years: mean 33; and <60 years: mean 31; p <
      0.0001) and 1 year post-implant (>=70 years: mean 77; 60 to 69 years: mean 72;
      <60 years: mean 70; p = 0.01) using the EQ-5D visual analog scale (VAS), with 0 =
      worst imaginable health state and 100 = best imaginable health state. The
      magnitude of improvement in EQ-5D scores from pre-implant to 1-year post-LVAD
      implant was similar in all age groups (>=70 years: mean change 33; 60 to 69
      years: mean change 35; <60 years: mean change 35; p = 0.77). Factors associated
      with improvement in HRQOL from before to 1 year after implant were a lower VAS
      score pre-implant and fewer rehospitalizations post-implant (R(2) = 61.3%, p <
      0.0001). CONCLUSIONS: Older patients reported better HRQOL than younger patients
      before and after LVAD implantation. The magnitude of improvement was similar for
      all age groups, with >70% of all patients showing clinically significant
      increases (>10 points on the VAS). Rehospitalization appears to reduce the
      magnitude of improvement.

PMID- 25578629
TI  - An efficient route to highly strained cyclobutenes: indium-catalyzed reactions of
      enynals with alkynes.
AB  - A catalytic method to synthesize the highly strained cyclobutene was developed.
      The reaction was believed to proceed through a formal indium-catalyzed [2+2]
      cycloaddition between electron-deficient enynals and various alkynes. 

PMID- 25578630
TI  - Statics and dynamics of electrowetting on pillar-arrayed surfaces at the
      nanoscale.
AB  - The statics and dynamics of electrowetting on pillar-arrayed surfaces at the
      nanoscale are studied using molecular dynamics simulations. Under a gradually
      increased electric field, a droplet is pushed by the electromechanical force to
      spread, and goes through the Cassie state, the Cassie-to-Wenzel wetting
      transition and the Wenzel state, which can be characterized by the electrowetting
      number at the microscale etam. The expansion of the liquid is direction-dependent
      and influenced by the surface topology. A positive voltage is induced in the bulk
      droplet, while a negative one is induced in the liquid confined among the
      pillars, which makes the liquid hard to spread and further polarize. Based on the
      molecular kinetic theory and the wetting states, theoretical models have been
      proposed to comprehend the physical mechanisms in the statics and dynamics of
      electrowetting, and are validated by our simulations. Our findings may help to
      understand the electrowetting on microtextured surfaces and assist the future
      design of engineered surfaces in practical applications. 

PMID- 25578628
TI  - Subjective evaluation of experimental dyspnoea--effects of isocapnia and repeated
      exposure.
AB  - Resistive respiratory loading is an established stimulus for the induction of
      experimental dyspnoea. In comparison to unloaded breathing, resistive loaded
      breathing alters end-tidal CO2 (P(ET)CO2), which has independent physiological
      effects (e.g. upon cerebral blood flow). We investigated the subjective effects
      of resistive loaded breathing with stabilized P(ET)CO2 (isocapnia) during manual
      control of inspired gases on varying baseline levels of mild hypercapnia
      (increased P(ET)CO2). Furthermore, to investigate whether perceptual habituation
      to dyspnoea stimuli occurs, the study was repeated over four experimental
      sessions. Isocapnic hypercapnia did not affect dyspnoea unpleasantness during
      resistive loading. A post hoc analysis revealed a small increase of respiratory
      unpleasantness during unloaded breathing at +0.6 kPa, the level that reliably
      induced isocapnia. We did not observe perceptual habituation over the four
      sessions. We conclude that isocapnic respiratory loading allows stable induction
      of respiratory unpleasantness, making it a good stimulus for multi-session
      studies of dyspnoea.

PMID- 25578631
TI  - Provider communication on perinatal depression: a population-based study.
AB  - Women's lack of knowledge on symptoms of perinatal depression and treatment
      resources is a barrier to receiving care. We sought to estimate the prevalence
      and predictors of discussing depression with a prenatal care provider. We used
      the 2011 population-based data from 24 sites participating in the Pregnancy Risk
      Assessment Monitoring System (n = 32,827 women with recent live births) to
      examine associations between maternal characteristics and report that a prenatal
      care provider discussed with her what to do if feeling depressed during or after
      pregnancy. Overall, 71.9 % of women reported discussing perinatal depression with
      their prenatal care provider (range 60.7 % in New York City to 85.6 % in Maine).
      Women were more likely to report a discussion on perinatal depression with their
      provider if they they were 18-29 years of age than over 35 years of age compared
      to older (adjusted prevalence ratio [aPR] 18 to 19 y = 1.08, 20 to 24 y = 1.10,
      25 to 29 y = 1.09), unmarried (aPR = 1.07) compared to married, had <12 years of
      education (aPR = 1.05) compared to > 12 years, and had no previous live births
      (aPR = 1.03) compared to >= 1 live births. Research is needed on effective ways
      to educate women about perinatal depression and whether increased knowledge on
      perinatal depression results in higher rates of treatment and shorter duration of
      symptoms.

PMID- 25578632
TI  - Maladaptive coping mediates the influence of childhood trauma on depression and
      PTSD among pregnant women in South Africa.
AB  - Antenatal mental disorders compromise maternal and child health, and women who
      have experienced childhood trauma may be at increased risk for such disorders.
      One hypothesis is that early trauma leads to the development and use of
      maladaptive coping strategies as an adult, which in turn could predict mental
      health difficulties during stressful transitions such as pregnancy. To test this
      hypothesis, this study examined the relationship between childhood trauma and
      mental health (depression, PTSD) in a sample of 84 pregnant women seeking
      antenatal care in Cape Town, South Africa, and explored whether maladaptive
      coping mediated this relationship. The majority of women (62 %) met established
      criteria for antenatal depression and 30 % for antenatal PTSD; in addition, 40 %
      reported a history of childhood trauma. Childhood trauma, especially childhood
      sexual abuse and emotional abuse, was significantly associated with depression
      and PTSD. The relationships between childhood trauma and depression and PTSD were
      significantly mediated by maladaptive coping, even when adjusted for the woman's
      age, gestational age, and HIV status. Findings highlight the need for coping
      based interventions to prevent and treat antenatal mental disorders among women
      with childhood trauma, particularly in high-trauma settings such as South Africa.

PMID- 25578635
TI  - Curcumin inhibits proliferation-migration of NSCLC by steering crosstalk between
      a Wnt signaling pathway and an adherens junction via EGR-1.
AB  - A microarray analysis of differential genes by curcumin treatment was performed
      and the crucial pathways associated with non-small cell lung cancer (NSCLC) were
      investigated. Total RNAs from 0, 10 or 20 MUM curcumin treated NSCLC 95D cells
      were used to prepare microarray chips. The differentially expressed genes (DEGs)
      were identified using the RankProducts package and their function was predicted
      by DAVID and gene set enrichment analysis. The pathway crosstalk was analyzed by
      mapping the gene expression profiles into protein-protein interaction databases.
      Validation of the microarray results was performed by cell viability, cell
      migration and western blot analyses. A total of 486 (10 MUM) and 264 (20 MUM)
      DEGs were screened between the 95D cells in the presence and absence of curcumin.
      Function enrichment analysis indicated the DEGs were mainly involved in the
      steroid biosynthetic process and regulation of autophagy. Pathway crosstalk
      analysis suggested there was a significant interaction between NSCLC and adherens
      junctions (or Wnt signaling pathways, which are important for cancer cell
      proliferation and invasion) in both 10 MUM and 20 MUM curcumin treated 95D cells.
      Furthermore, early growth response (EGR-1) was demonstrated to regulate the
      crosstalk between adherens junctions and Wnt signaling pathways, indicating that
      EGR-1 may also regulate cell proliferation and migration. This hypothesis was
      validated by in vitro experiments: EGR-1 was decreased after curcumin treatment.
      Curcumin exhibited a significant anti-proliferation and anti-migration activity
      in NSCLC 95D cells, possibly by steering the crosstalk between the Wnt signaling
      pathway and adherens junction via EGR-1. 

PMID- 25578634
TI  - Improved approach for chondrogenic differentiation of human induced pluripotent
      stem cells.
AB  - Human induced pluripotent stem cells (hiPSCs) have demonstrated great potential
      for hyaline cartilage regeneration. However, current approaches for chondrogenic
      differentiation of hiPSCs are complicated and inefficient primarily due to
      intermediate embryoid body formation, which is required to generate endodermal,
      ectodermal, and mesodermal cell lineages. We report a new, straightforward and
      highly efficient approach for chondrogenic differentiation of hiPSCs, which
      avoids embryoid body formation. We differentiated hiPSCs directly into
      mesenchymal stem /stromal cells (MSC) and chondrocytes. hiPSC-MSC-derived
      chondrocytes showed significantly increased Col2A1, GAG, and SOX9 gene expression
      compared to hiPSC-MSCs. Following transplantation of hiPSC-MSC and hiPSC-MSC
      derived chondrocytes into osteochondral defects of arthritic joints of athymic
      rats, magnetic resonance imaging studies showed gradual engraftment, and
      histological correlations demonstrated hyaline cartilage matrix production.
      Results present an efficient and clinically translatable approach for cartilage
      tissue regeneration via patient-derived hiPSCs, which could improve cartilage
      regeneration outcomes in arthritic joints. 

PMID- 25578636
TI  - Perineural spreading along the trigeminal nerve in a squamous cell carcinoma of
      the tongue.

PMID- 25578637
TI  - The role of P300 event-related potentials in the cognitive recovery after the
      stroke.
AB  - The aim of this study was to elucidate the effects of an ischemic stroke on the
      amplitude and latency of the P300 wave and evaluate their changes over a
      prospective 1-year follow-up period. We recorded the P300 wave using an auditory
      oddball paradigm in 60 consecutive brain infarct patients at baseline (i.e.,
      within 4 weeks after the stroke), after 3 months, after 12 months and in 30
      healthy control subjects. The P300 latencies in stroke patients were
      significantly longer and the P300 amplitudes were significantly smaller than
      those of the control group. The latency of P300 showed a highly significant
      average improvement 12 months after the stroke compared to the baseline. There
      was no significant change observed for the P300 amplitude during the same period.
      The P3 latency is initially more increased in the patients with hemispheric brain
      infarction but shows a better recovery compared to the patients with brainstem
      infarction. Also, the results of the P300 latency of patients with the left-sided
      lesions was significantly longer compared to the patients with right-sided
      lesions on the beginning of the study but not 3 and 12 months after the stroke.
      The results of our study show the importance of P300 event-related potentials in
      the detection and follow-up of cognitive changes after ischemic stroke.

PMID- 25578638
TI  - Comment on "Relationship between non-alcoholic fatty liver disease and benign
      prostatic hyperplasia/lower urinary tract symptoms: new insights from an Italian
      cross-sectional study".

PMID- 25578643
TI  - Spanish consensus on premature menopause.
AB  - INTRODUCTION: While we recognise that the term premature menopause is more
      accepted by most non-specialist health care providers and by the general
      population, 'primary ovarian insufficiency' (POI) is currently considered the
      most apposite term to explain the loss of ovarian function, because it better
      explains the variability of the clinical picture, does not specify definitive
      failure, and highlights the specific ovarian source. Its pathogenesis involves a
      congenital reduction in the number of primordial follicles, poor follicle
      recruitment, or accelerated follicular apoptosis. However, its cause is unknown
      in most cases. AIM: This guide analyses the factors associated with the diagnosis
      and treatment of POI and provides recommendations on the most appropriate
      diagnostic and therapeutic measures for women under 40 years of age who
      experience POI. METHODOLOGY: A panel of experts from various Spanish scientific
      societies related to POI (Spanish Menopause Society, Spanish Fertility Society,
      and Spanish Contraception Society) met to reach a consensus on these issues.
      RESULTS: Hormonal therapy (HT) is considered the treatment of choice to alleviate
      the symptoms of hypoestrogenism and to prevent long-term consequences. We suggest
      that HT should be continued until at least age 51, the average age at natural
      menopause. The best treatment to achieve pregnancy is oocyte/embryo donation. If
      a patient is to undergo treatment that will reduce her fertility, she should be
      informed of this issue and the available techniques to preserve ovarian function,
      mainly vitrification of oocytes.

PMID- 25578644
TI  - The effect of endotoxin on heart rate dynamics in diabetic rats.
AB  - The effect of endotoxin on heart rate variability (HRV) was assessed in diabetic
      and controls rats using a telemetric system. Endotoxin induced a reduction in
      sample entropy of cardiac rhythm in control animals. However, this effect was
      significantly blunted in streptozotocin-induced diabetic rats. Since uncoupling
      of cardiac pacemaker from cholinergic control is linked to reduced HRV in
      endotoxemia, chronotropic responsiveness to cholinergic stimulation was assessed
      in isolated atria. Endotoxemia was associated with impaired responsiveness to
      carbacholine in control rats. However, endotoxemia did not impair cholinergic
      responsiveness in diabetic atria. These findings corroborates with development of
      endotoxin tolerance in diabetic rats. 

PMID- 25578645
TI  - Comparison of Renal Parenchymal Volume Preservation Between Partial Nephrectomy,
      Cryoablation, and Radiofrequency Ablation Using 3D Volume Measurements.
AB  - PURPOSE: Small renal masses (SRM) can be managed via a variety of nephron-sparing
      procedures (NSPs), but the association between choice of NSP and renal
      parenchymal volume (RPV) preservation is not well understood. We sought to
      examine RPV preservation after partial nephrectomy (PN) performed via open,
      robotic, or laparoscopic approaches and thermal ablation (TA) performed via
      cryoablation (CA) or radiofrequency ablation (RFA). PATIENTS AND METHODS: The
      study was a retrospective review of three institutional databases of patients
      with a SRM <4 cm treated via one of the five NSPs (open PN, laparoscopic PN,
      robotic PN, percutaneous CA, or percutaneous RFA). The 30 most recent consecutive
      cases treated via each NSP were selected to obtain a total of 150 cases for
      analysis. Patient characteristics were obtained via manual chart review, and
      tumor characteristics were assessed via the R.E.N.A.L. nephrometry score. Using
      three-dimensional rendering software, preoperative and postoperative RPV was
      calculated for the tumor-bearing kidney, excluding the tumor itself (for
      preoperative images) or the postsurgical/ablative defect (for postoperative
      images). The percent change in RPV was compared between the procedure types.
      RESULTS: One hundred fifty cases were included in the final analysis, with 30
      cases from each NSP category. While preoperative tumors were larger in the PN
      group, there was no difference in the mean nephrometry score between groups. The
      TA group was found to have a lower mean RPV loss (-8.1% vs -16.5%, p<0.005).
      There was no difference in the RPV loss between modalities of TA (CA vs RFA) or
      between approaches to PN (open, laparoscopic, robotic). Matched-pair analysis
      based on the tumor size and multivariate analysis indicated TA vs PN was
      independently associated with less RPV loss. CONCLUSIONS: TA is associated with
      less RPV loss than PN in the management of SRM, but there is no difference
      between modalities of TA (CA vs RFA) or between approaches to PN.

PMID- 25578647
TI  - Letter to the Editor: Caspase cleavage sites in the human proteome: CaspDB, a
      database of predicted substrates.

PMID- 25578648
TI  - S-nitrosylation of XIAP at Cys 213 of BIR2 domain impairs XIAP's anti-caspase 3
      activity and anti-apoptotic function.
AB  - X-linked inhibitor of apoptosis (XIAP) is a protein that possesses anti-apoptotic
      function and dysregulation of it has been linked to a number human disease such
      as cancers and neurodegenerative disorders. In our previous study, we have found
      that nitric oxide (NO) can modulate the anti-apoptotic function of XIAP and found
      that this can contribute to the pathogenesis of Parkinson's disease.
      Specifically, we found that modification of baculoviral IAP repeat 2 of XIAP by S
      nitrosylation can compromise XIAP's anti-caspase 3 and anti-apoptotic function.
      In this study, we report that cysteine (Cys) 90, Cys 213 and Cys 327 can be
      specifically S-nitrosylated by NO. We found that mutations of Cys 90 and Cys 327
      affect the normal structure of XIAP. More importantly, we found that S
      nitrosylation of XIAP Cys 213 impairs the anti-caspase 3 and anti-apoptotic
      function of XIAP that we observed in our previous study. 

PMID- 25578646
TI  - Psychopathology research in the RDoC era: Unanswered questions and the importance
      of the psychophysiological unit of analysis.
AB  - The NIMH Research Domain Criteria (RDoC) initiative seeks to re-conceptualize
      psychopathology by identifying transdiagnostic constructs that reflect core
      mechanisms of psychopathology. Although the RDoC framework has been discussed in
      many prior papers, there are several methodological and conceptual points that
      have yet to be fully specified. For example, little discussion exists on the
      importance of distinguishing each construct's nomological network and linking it
      to risk for psychopathology. It has also been unclear the extent to which RDoC
      constructs (within and across systems) should relate to one another and how these
      associations may differ as a function of developmental period. These are
      important questions as we enter the RDoC era and psychophysiological measures
      represent an exciting tool to address these issues. In this paper, we discuss the
      currently un- (or under-)specified aspects of the RDoC initiative and highlight
      the advantages of the psychophysiological 'unit of analysis.' We also briefly
      review existing psychophysiological studies, within the positive and negative
      valence systems, that exemplify the RDoC approach and make recommendations for
      how future studies can help the field progress in this mission. 

PMID- 25578649
TI  - Cancer of the sigmoid colon and antibodies. A puzzle.
AB  - In this work we describe the case report of a woman affected by cancer of the
      sigmoid colon and with a positive direct antiglobulin test (DAT) and indirect
      antiglobulin test (IAT). Case report with results: A meticulous medical history
      showed that the woman had been suffering from recurrent fetal loss. Then she had
      cardiac and coagulative problems. These data suggested a phospholipid syndrome.
      CONCLUSION: The patient had a medical history positive for a phospholipid
      syndrome and we think that this disease could explain the onset of the
      autoantibody.

PMID- 25578650
TI  - Micro gel column technique is fit for detecting mixed fields post ABO
      incompatible hematopoietic stem cell transplantation.
AB  - How to choose suitable serologic method for assessment of the actual stages of
      ABO chimera is more important to establish transfusion strategy for patients post
      ABO incompatible hematopoietic stem cell transplantation. We reported ABO
      phenotypes of a patient post-ABO minor incompatible hematopoietic stem cell
      transplantation from 1+ weak agglutination by tube method was obviously
      reaffirmed to mixed fields with 4+ positive reaction by micro gel column card.
      Hence, blood bank technologists must continually work together with hematologist
      to establish appropriate transfusion strategy, and micro gel column technique can
      be more appropriate for detecting mixed fields during the whole period of
      transplantation. 

PMID- 25578651
TI  - Apheretic "rescue-protocol" designed for treatment of CLL associated life
      threatening hemolytic crisis.

PMID- 25578652
TI  - Successful treatment of a 3-year-old boy with hepatitis-associated aplastic
      anemia with combination of auto-umbilical cord blood transplantation and
      immunosuppressive therapy.
AB  - In this work we describe a 3-year-old boy with hepatitis-associated aplastic
      anemia (HAAA) treated successfully with autologous cord blood transplantation
      combined with immunosuppressive therapy. There is little previous experience in
      the utility of autologous cord blood transplantation in the treatment of HAAA.
      Nowadays, for patients born after 1980, an HLA matched sibling donor is not
      usually available because of the family planning policy in our country. So more
      and more parents choose to preserve the umbilical cord blood for their children.
      We consider it a new effective choice for the treatment of HAAA, especially for
      the pediatric patients. 

PMID- 25578654
TI  - Isotope-reinforced polyunsaturated fatty acids protect mitochondria from
      oxidative stress.
AB  - Polyunsaturated fatty acid (PUFA) peroxidation is initiated by hydrogen atom
      abstraction at bis-allylic sites and sets in motion a chain reaction that
      generates multiple toxic products associated with numerous disorders. Replacement
      of bis-allylic hydrogens of PUFAs with deuterium atoms (D-PUFAs), termed site
      specific isotope reinforcement, inhibits PUFA peroxidation and confers cell
      protection against oxidative stress. We demonstrate that structurally diverse
      deuterated PUFAs similarly protect against oxidative stress-induced injury in
      both yeast and mammalian (myoblast H9C2) cells. Cell protection occurs
      specifically at the lipid peroxidation step, as the formation of isoprostanes,
      immediate products of lipid peroxidation, is drastically suppressed by D-PUFAs.
      Mitochondrial bioenergetics function is a likely downstream target of oxidative
      stress and a subject of protection by D-PUFAs. Pretreatment of cells with D-PUFAs
      is shown to prevent inhibition of maximal uncoupler-stimulated respiration as
      well as increased mitochondrial uncoupling, in response to oxidative stress
      induced by agents with diverse mechanisms of action, including t
      butylhydroperoxide, ethacrynic acid, or ferrous iron. Analysis of structure
      activity relationships of PUFAs harboring deuterium at distinct sites suggests
      that there may be a mechanism supplementary to the kinetic isotope effect of
      deuterium abstraction off the bis-allylic sites that accounts for the protection
      rendered by deuteration of PUFAs. Paradoxically, PUFAs with partially deuterated
      bis-allylic positions that retain vulnerable hydrogen atoms (e.g., monodeuterated
      11-D1-Lin) protect in a manner similar to that of PUFAs with completely
      deuterated bis-allylic positions (e.g., 11,11-D2-Lin). Moreover, inclusion of
      just a fraction of deuterated PUFAs (20-50%) in the total pool of PUFAs preserves
      mitochondrial respiratory function and confers cell protection. The results
      indicate that the therapeutic potential of D-PUFAs may derive from the
      preservation of mitochondrial function. 

PMID- 25578653
TI  - CDK4-mediated MnSOD activation and mitochondrial homeostasis in radioadaptive
      protection.
AB  - Mammalian cells are able to sense environmental oxidative and genotoxic
      conditions such as the environmental low-dose ionizing radiation (LDIR) present
      naturally on the earth's surface. The stressed cells then can induce a so-called
      radioadaptive response with an enhanced cellular homeostasis and repair capacity
      against subsequent similar genotoxic conditions such as a high dose radiation.
      Manganese superoxide dismutase (MnSOD), a primary mitochondrial antioxidant in
      mammals, has long been known to play a crucial role in radioadaptive protection
      by detoxifying O2(*-) generated by mitochondrial oxidative phosphorylation. In
      contrast to the well-studied mechanisms of SOD2 gene regulation, the mechanisms
      underlying posttranslational regulation of MnSOD for radioprotection remain to be
      defined. Herein, we demonstrate that cyclin D1/cyclin-dependent kinase 4 (CDK4)
      serves as the messenger to deliver the stress signal to mitochondria to boost
      mitochondrial homeostasis in human skin keratinocytes under LDIR-adaptive
      radioprotection. Cyclin D1/CDK4 relocates to mitochondria at the same time as
      MnSOD enzymatic activation peaks without significant changes in total MnSOD
      protein level. The mitochondrial-localized CDK4 directly phosphorylates MnSOD at
      serine-106 (S106), causing enhanced MnSOD enzymatic activity and mitochondrial
      respiration. Expression of mitochondria-targeted dominant negative CDK4 or the
      MnSOD-S106 mutant reverses LDIR-induced mitochondrial enhancement and adaptive
      protection. The CDK4-mediated MnSOD activation and mitochondrial metabolism boost
      are also detected in skin tissues of mice receiving in vivo whole-body LDIR.
      These results demonstrate a unique CDK4-mediated mitochondrial communication that
      allows cells to sense environmental genotoxic stress and boost mitochondrial
      homeostasis by enhancing phosphorylation and activation of MnSOD. 

PMID- 25578655
TI  - RTG1- and RTG2-dependent retrograde signaling controls mitochondrial activity and
      stress resistance in Saccharomyces cerevisiae.
AB  - Mitochondrial retrograde signaling is a communication pathway between the
      mitochondrion and the nucleus that regulates the expression of a subset of
      nuclear genes that codify mitochondrial proteins, mediating cell response to
      mitochondrial dysfunction. In Saccharomyces cerevisiae, the pathway depends on
      Rtg1p and Rtg3p, which together form the transcription factor that regulates gene
      expression, and Rtg2p, an activator of the pathway. Here, we provide novel
      studies aimed at assessing the functional impact of the lack of RTG-dependent
      signaling on mitochondrial activity. We show that mutants defective in RTG
      dependent retrograde signaling present higher oxygen consumption and reduced
      hydrogen peroxide release in the stationary phase compared to wild-type cells.
      Interestingly, RTG mutants are less able to decompose hydrogen peroxide or
      maintain viability when challenged with hydrogen peroxide. Overall, our results
      indicate that RTG signaling is involved in the hormetic induction of antioxidant
      defenses and stress resistance. 

PMID- 25578670
TI  - Variation in the incidence of pulmonary embolism and related mortality depending
      on the season and day of the week.

PMID- 25578671
TI  - The day of elias.

PMID- 25578669
TI  - Sustainable employability in shiftwork: related to types of work schedule rather
      than age.
AB  - PURPOSE: There is scarce research on age and sustainable employability of nurses
      working in various types of work schedules. Earlier research showed that nurses
      working in work schedules differ regarding age. Different operationalisations of
      age might explain variations in sustainable employability. Therefore, the aim of
      this study was to investigate how nurses working in various types of work
      schedule differ regarding sustainable employability, and the role that age plays
      in these differences. Age was defined as chronological age, organisational age,
      life-span age, and functional age. METHOD: Questionnaires were distributed to 974
      Dutch nurses in residential elder care (response rate 51 %) with questions about
      the type of work schedule, aspects of sustainable employability, various
      operationalisations of age, and registered sickness absence data were used.
      RESULTS: Nurses working in various types of work schedules differed regarding
      aspects of sustainable employability, also when operationalisations of age were
      added. The 'life-span age' was directly related to aspects of sustainable
      employability. Statistically, work ability and job satisfaction were only
      explained by varying operationalisations of age. CONCLUSIONS: Nurses' sustainable
      employability appeared to be mainly related to differences between the types of
      work schedule rather than age. Fixed early shifts are characterised by the most
      positive aspects of sustainable employability, and three rotating schedules score
      worst. To improve sustainable employability, organisations should implement a
      system in which nurses with different types of work schedule are monitored in
      combination with their life-span perspective.

PMID- 25578672
TI  - It has been said.

PMID- 25578673
TI  - The Creation Story-a Biologist's View.

PMID- 25578674
TI  - A palindrome of pathologists.

PMID- 25578675
TI  - Ethics for authors: a case history of acrosin.

PMID- 25578676
TI  - Circle and Circulation: The Language and Imagery of William Harvey's Discovery.

PMID- 25578677
TI  - The function of medical-care systems: a logical analysis.

PMID- 25578679
TI  - Multiple imputation: a mature approach to dealing with missing data.

PMID- 25578678
TI  - Prognosis of neutropenic patients admitted to the intensive care unit.
AB  - PURPOSE: The prognosis of critically ill cancer patients has improved recently.
      Controversies remain as regard to the specific prognosis impact of neutropenia in
      critically ill cancer patients. The primary objective of this study was to assess
      hospital outcome of critically ill neutropenic cancer patients admitted into the
      ICU. The secondary objective was to assess risk factors for unfavorable outcome
      in this population of patients and specific impact of neutropenia. METHODS: We
      performed a post hoc analysis of a prospectively collected database. The study
      was carried out in 17 university or university-affiliated centers in France and
      Belgium. Neutropenia was defined as a neutrophil count lower than 500/mm(3).
      RESULTS: Among the 1,011 patients admitted into the ICU during the study period
      289 were neutropenic at the time of admission. Overall, 131 patients died during
      their hospital stay (hospital mortality 45.3 %). Four variables were associated
      with a poor outcome, namely allogeneic transplantation (OR 3.83; 95 % CI 1.75
      8.35), need for mechanical ventilation (MV) (OR 6.57; 95 % CI 3.51-12.32),
      microbiological documentation (OR 2.33; CI 1.27-4.26), and need for renal
      replacement therapy (OR 2.77; 95 % CI 1.34-5.74). Two variables were associated
      with hospital survival, namely age younger than 70 (OR 0.22; 95 % CI 0.1-0.52)
      and neutropenic enterocolitis (OR 0.37; 95 % CI 0.15-0.9). A case-control
      analysis was also performed with patients of the initial database; after
      adjustment, neutropenia was not associated with hospital mortality (OR 1.27; 95 %
      CI 0.86-1.89). CONCLUSION: Hospital survival was closely associated with younger
      age and neutropenic enterocolitis. Conversely, need for conventional MV, for
      renal replacement therapy, and allogeneic hematopoietic stem cell transplantation
      (HSCT) were associated with poor outcome.

PMID- 25578680
TI  - Efficacy and safety of reslizumab in patients with moderate to severe
      eosinophilic asthma.
AB  - Reslizumab, a neutralizing anti-IL-5 monoclonal antibody, is a promising
      adjunctive treatment for severe eosinophilic asthma. Monthly intravenous 3.0
      mg/kg reslizumab had resulted in improvements in lung function and asthma
      control. It is well tolerated and common adverse events include headache,
      nasopharyngitis and upper respiratory tract infection. Rebound eosinophilia after
      cessation of reslizumab and attenuation of the treatment response with repeated
      dosing had been reported. Stringent selection of patients with a high eosinophil
      burden, who are poorly controlled despite moderate to high doses of inhaled
      corticosteroid, confers the most significant treatment response. Future trials
      should compare the dose, delivery platform, frequency of dosing and study
      combinations with other biologics, which will affect its maximal clinical
      efficacy. 

PMID- 25578683
TI  - Radial scar/complex sclerosing lesions: a clinicopathologic correlation study
      from a single institution.
AB  - Radial scars (RSs) or complex sclerosing lesions (CSLs) of the breast are benign
      radiologic and histologic entities. With the introduction of population-based
      screening programs, their incidence has increased to 0.03% to 0.09% of all core
      needle biopsies (CNBs). They can pose diagnostic difficulty because their
      radiologic and histologic appearances mimic carcinoma. We retrospectively
      searched for and reviewed all cases of RS/CSL diagnosed on image-guided CNB from
      January 1, 1994, to August 31, 2013, at a single institution. We also assessed
      the pathologic reports from excisional biopsies to identify cases upstaged to
      atypia or neoplasm. After exclusions, 100 CNBs were identified from 97 women,
      which showed RS/CSL without concomitant atypia. Mean age of the women was 52.9
      years. Thirty-five women (38/100 CNBs, 38%) had follow-up excision. The median
      size of the excised RS/CSLs was 1.2 cm; 69% were larger than 1.0 cm. Almost all
      excised cases (92%) showed radiologic and pathologic concordance, and 79% were
      designated as suspicious for malignancy (Breast Imaging Reporting and Data System
      level 4). The most common findings of 38 follow-up excisional biopsies were
      residual RS (22 [58%]), atypical lobular hyperplasia (5 [13%]), and no residual
      lesion (5 [13%]). Eleven excisional biopsies (29%) were upstaged to invasive or
      in situ carcinoma or to atypical hyperplasia. Follow-up excisional biopsy is
      warranted for RS/CSLs, specifically those larger than 1.0 cm with worrisome
      radiographic findings or with radiologic and pathologic discordance.
      Approximately 29% of cases were upstaged to in situ or invasive carcinomas or
      other high-risk lesions in our study. 

PMID- 25578684
TI  - Airborne transmission and precautions: facts and myths.
AB  - Airborne transmission occurs only when infectious particles of <5 MUm, known as
      aerosols, are propelled into the air. The prevention of such transmission is
      expensive, requiring N95 respirators and negative pressure isolation rooms. This
      lecture first discussed whether respiratory viral infections are airborne with
      reference to published reviews of studies before 2008, comparative trials of
      surgical masks and N95 respirators, and relevant new experimental studies.
      However, the most recent experimental study, using naturally infected influenza
      volunteers as the source, showed negative results from all the manikins that were
      exposed. Modelling studies by ventilation engineers were then summarized to
      explain why these results were not unexpected. Second, the systematic review
      commissioned by the World Health Organization on what constituted aerosol
      generating procedures was summarized. From the available evidence, endotracheal
      intubation either by itself or combined with other procedures (e.g.
      cardiopulmonary resuscitation or bronchoscopy) was consistently associated with
      increased risk of transmission by the generation of aerosols.

PMID- 25578685
TI  - Epidemiology of meticillin-resistant Staphylococcus aureus bloodstream infections
      in Alberta, Canada.
AB  - Most studies of meticillin-resistant Staphylococcus aureus (MRSA) bloodstream
      infection (BSI) reflect a convenience sample from a single hospital or a small
      group of hospitals. From April 2011 to March 2013, cases of MRSA BSI diagnosed in
      all hospitals in Alberta, Canada were captured prospectively. Isolates were spa
      typed. In total, there were 299 cases of MRSA BSI, equating to 3.95 cases per
      100,000 population. Community-acquired BSI accounted for 66.9% of cases, and
      33.1% of cases were hospital acquired. Cases were predominantly seen in tertiary
      care (36.4%) and large urban hospitals (34.3%), but were also common in regional
      and rural hospitals. Paediatric hospitals had very few cases (3.0%). Two clones,
      CMRSA 10 (USA 300; 40.2%) and CMRSA 2 (USA 100/800; 38.0%), predominated. 

PMID- 25578686
TI  - Beneficial effects of quercetin on oxidative stress in liver and kidney induced
      by titanium dioxide (TiO2) nanoparticles in rats.
AB  - TiO2 nanoparticles used as vectors for the delivery of drugs have shown greater
      effectiveness. However, TiO2 nanoparticles can cause oxidative stress in liver
      and kidney, so we analyzed if a previous or simultaneous quercetin treatment
      could counteract this in rats. Five groups of male Wistar rats (200-250 g) were
      included: (1) healthy controls, (2) TiO2 group, (3) quercetin group, (4)
      preventive group: quercetin for 5 days prior to exposure of TiO2, and (5)
      therapeutic group: TiO2 (5 mg/kg, i.v.) plus quercetin single dose for 5 days (5
      mg/kg/day, i.p.). Hepatic and renal function tests were made. Five animals from
      each group were sacrificed (0, 14 and 28 days), and liver and kidney tissue were
      obtained. Malondialdehyde (MDA), reduced/oxidized glutathione, and activity of
      glutathione peroxidase/reductase were measured, as well as the level of gene
      expression by q-PCR. There were no significant changes in serum ALT and AST
      activities. More damage was observed at 14 versus 28 days, because TiO2 was
      excreted in urine. Quercetin indeed showed a renal protective effect by
      increasing glutathione reductase and peroxidase levels and reducing MDA levels.
      On the other hand, TiO2 liver damage was less pronounced with quercetin as
      therapeutic treatment. TiO2 induces significantly the glutathione reductase
      expression and it can be down-regulated by quercetin. Biochemical tests in serum
      and urine showed a better effect of quercetin administered in the therapeutic
      group. Care should be taken with the dose and time of administration of
      quercetin, because this antioxidant could also have a pro-oxidant effect.

PMID- 25578691
TI  - Structural and biological evaluation of lignin addition to simple and silver
      doped hydroxyapatite thin films synthesized by matrix-assisted pulsed laser
      evaporation.
AB  - We report on thin film deposition by matrix-assisted pulsed laser evaporation of
      simple hydroxyapatite (HA) or silver (Ag) doped HA combined with the natural
      biopolymer organosolv lignin (Lig) (Ag:HA-Lig). Solid cryogenic target of aqueous
      dispersions of Ag:HA-Lig composite and its counterpart without silver (HA-Lig)
      were prepared for evaporation using a KrF* excimer laser source. The expulsed
      material was assembled onto TiO2/Ti substrata or silicon wafers and subjected to
      physical-chemical investigations. Smooth, uniform films adherent to substratum
      were observed. The chemical analyses confirmed the presence of the HA components,
      but also evidenced traces of Ag and Lig. Deposited HA was Ca deficient, which is
      indicative of a film with increased solubility. Recorded X-ray Diffraction
      patterns were characteristic for amorphous films. Lig presence in thin films was
      undoubtedly proved by both X-ray Photoelectron and Fourier Transform Infra-Red
      Spectroscopy analyses. The microbiological evaluation showed that the newly
      assembled surfaces exhibited an inhibitory activity both on the initial steps of
      biofilm forming, and on mature bacterial and fungal biofilm development. The
      intensity of the anti-biofilm activity was positively influenced by the presence
      of the Lig and/or Ag, in the case of Staphylococcus aureus, Pseudomonas
      aeruginosa and Candida famata biofilms. The obtained surfaces exhibited a low
      cytotoxicity toward human mesenchymal stem cells, being therefore promising
      candidates for fabricating implantable biomaterials with increased
      biocompatibility and resistance to microbial colonization and further biofilm
      development.

PMID- 25578692
TI  - Hollow hydroxyapatite microspheres/chitosan composite as a sustained delivery
      vehicle for rhBMP-2 in the treatment of bone defects.
AB  - Composite scaffold comprised of hollow hydroxyapatite (HA) and chitosan
      (designated hHA/CS) was prepared as a delivery vehicle for recombinating human
      bone morphogenetic protein-2 (rhBMP-2). The in vitro and in vivo biological
      activities of rhBMP2 released from the composite scaffold were then investigated.
      The rhBMP-2 was firstly loaded into the hollow HA microspheres, and then the
      rhBMP2-loaded HA microspheres were further incorporated into the chitosan matrix.
      The chitosan not only served to bind the HA microspheres together and kept them
      at the implant site, but also effectively modified the release behavior of rhBMP
      2. The in vitro release and bioactivity analysis confirmed that the rhBMP2 could
      be loaded and released from the composite scaffolds in bioactive form. In
      addition, the composite scaffolds significantly reduced the initial burst release
      of rhBMP2, and thus providing prolonged period of time (as long as 60 days)
      compared with CS scaffolds. In vivo bone regenerative potential of the rhBMP2
      loaded composite scaffolds was evaluated in a rabbit radius defect model. The
      results revealed that the rate of new bone formation in the rhBMP2-loaded hHA/CS
      group was higher than that in both negative control and rhBMP2-loaded CS group.
      These observations suggest that the hHA/CS composite scaffold would be effective
      and feasible as a delivery vehicle for growth factors in bone regeneration and
      repair.

PMID- 25578693
TI  - Vertical bone regeneration with deproteinised bovine bone mineral or biphasic
      calcium phosphate in the rabbit calvarium: effect of autologous platelet lysate.
AB  - Although bone substitutes associated with platelet concentrates are widely used
      to vertically reconstruct alveolar ridges, their respective and specific
      contribution remain controversial. The aim of this study was to evaluate the
      benefit of using either biphasic calcium phosphate (BCP) or demineralised bovine
      bone mineral (DBBM) alone or with autologous platelet lysate (APL) in vertical
      bone regeneration. The study involved fourteen New Zealand rabbits. Autologous
      APL was prepared by freeze-thawing from a platelet suspension (10(9)
      platelets/ml). Four CP titanium (cpTi) cylinders were fixed to each calvarium;
      one cylinder was empty, one was filled with APL alone and the others were filled
      either with BCP or BCP + APL or DBBM or DBBM + APL. New bone formation and
      biomaterial resorption were evaluated using non-demineralised histology and
      histomorphometry. After 6 weeks, new bone formation was observed in all
      cylinders. The newly formed bone in the cylinders filled with APL alone, DBBM and
      BCP was significantly increased by (0.6-, 2.5- and 3.3-fold, respectively) (P <
      0.0001) compared to results obtained with the empty cylinders. Vertical bone
      height in the cylinders filled with BCP was greater to that observed with DBBM.
      The residual material in the cylinders filled with BCP was significantly (P <
      0.0001) lower (0.35-fold) than that with DBBM. Both newly formed bone and
      residual material in the cylinders filled with BCP + APL or DBBM + APL were
      similar to those filled with either BCP or DBBM, respectively. This study
      provided evidence that APL alone, as well as DBBM and BCP, have a beneficial
      effect on vertical bone formation and remodelling. APL associated with either
      DBBM or BCP did not provide additional benefits.

PMID- 25578694
TI  - An alternative to nerve repair using an antioxidant compound: a histological
      study in rats.
AB  - The fascicular composition and organisation of the inferior alveolar nerve (IAN)
      were determined to confirm the microarchitecture of the IAN bundles into each of
      the mandibular teeth, including the composition of the mental nerve. The aim of
      this study was to evaluate peripheral nerve repair after the application of an
      antioxidant compound to the damaged nerve tissue to elevate the concentration and
      bioavailability of elements capable of favouring tissue repair. Twenty-five
      Wistar rats were divided into groups: The Control 1 (Ctl 1) (n = 5) animals had
      the ischiatic nerve exposed with no suture injury and were sacrificed at 30 days
      post-operatively. The Control 2 (Ctl 2) (n = 10) animals had the ischiatic nerve
      exposed, and the nerve was injured using suture in three distinct regions. In the
      experimental (Exp) animals (n = 10), an antioxidant organic compound was applied
      to the nerve injury site. The animals with nerve injury (Ctl2 and Exp group) were
      sacrificed at 15 and 30 days post-operatively. The histological analysis showed
      less degeneration in the Exp group at 15 and 30 days post-operatively. Nerve
      neoformation forming a connection between the distal and proximal suture sites
      was observed in the experimental group. This study presented an alternative to
      nerve repair using an antioxidant compound.

PMID- 25578695
TI  - Inhibition of hydroxyapatite formation in the presence of titanocene-amino acid
      complexes: an experimental and computational study.
AB  - Organometallic compounds have been used in various fields of chemistry, medicine
      and materials science. Central metal, stereochemical configuration and functional
      groups of the substitutes give to the organometallic compounds very special and
      selective properties. These properties have been used successfully in selective
      antitumor-targeting, as well as anti-arthritic drugs. In the present
      investigation we study the influence of two organometallic compounds on the
      inhibition of crystallization of hydroxyapatite. These compounds are complexes of
      Ti(IV) with the general formula [Cp2Ti(aa)2](2+)2Cl(-), where Cp = eta (5)-C5H5
      cyclopentadienyl and aa the amino acid glycine or alanine. The experiments were
      conducted according to the constant composition technique in supersaturated
      solutions containing calcium and phosphate ions. The kinetic results indicate a
      surface diffusion controlled mechanism of the hydroxyapatite (HAP) crystals. The
      experiments prove that the presence of [Cp2Ti(Ala)2](2+)2Cl(-) and
      [Cp2Ti(Gly)2](2+)2Cl(-) complexes affects drastically the profile formation rate
      of the HAP crystals under biological conditions. The complex with the amino acid
      alanine provides a stronger inhibition of the formation rate comparing to the
      complex with glycine. The experimental observations are supported by computer
      calculations. 

PMID- 25578696
TI  - Evaluation of a new Mg-Zn-Ca-Y alloy for biomedical application.
AB  - In this study, a new Mg-Zn-Ca-Y alloy was evaluated for blood compatibility and
      in vivo biocompatibility in rabbits after implantation in the sacral crest
      muscle. Blood test and HE staining was performed to examine the host response,
      and scanning electron microscope was used to observe the fibrous membrane and
      corrosion of the magnesium alloy. The results showed that hemolysis rate
      decreased with the Mg(2+) concentration, in particularly, the hemolysis rate was
      47.24 % for the magnesium alloy 100 % mixture solution, while was 0.1372 % for
      the 1 % extract solution. After implantation, the rabbits showed generally good
      condition, without swelling and wound secretions. One week after implantation, in
      the experimental group, a few lymphocytes and macrophages could be observed
      around the local muscle tissue, and fiber membrane structure had not yet formed;
      after 2 weeks, loose fiber membranes formed, while the number of inflammatory
      cells decreased; the fiber membrane became thinner at 4 and 12 weeks,. The fiber
      membrane thickness at 24 weeks were measured by scanning electron microscopy, at
      about 15-25 MUm, which accord with the U.S. ASTM-F4 implant requirements (<30
      MUm). Acceptable degradation and corrosion were observed after implantation into
      rabbits. Through the in vivo study, the new magnesium alloy exhibited good
      biocompatibility and non-toxic in the experimental animals. Addition of Zn, Ca
      and Y can slow the degradation rate, and have acceptable side effects in vivo,
      resulting in improved corrosion properties and desirable biocompatibility at the
      same time.

PMID- 25578697
TI  - In vitro assessment of the antimicrobial activity of wound dressings: influence
      of the test method selected and impact of the pH.
AB  - Antibacterial activity of dressings containing antimicrobials is mostly evaluated
      using in vitro tests. However, the various methods available differ significantly
      in their properties and results obtained are influenced by the method selected,
      micro-organisms used, and extraction method, the degree of solubility or the
      diffusability of the test-compounds. Here, results on antimicrobial activity of
      silver-containing dressings obtained by agar diffusion test (ADT), challenge
      tests (JIS L 1902, AATCC 100), and extraction-based methods (microplate laser
      nephelometry (MLN), luminescent quantification of bacterial ATP (LQbATP)) using
      Staphylococcus aureus and Pseudomonas aeruginosa were evaluated. Furthermore, the
      effect of the pH on antibacterial efficacy of these dressings was investigated.
      All silver-containing dressings exerted antimicrobial activity in all in vitro
      tests and results correlated considerably well. Differences were observed testing
      the agent-free basic materials. They did not exhibit any antimicrobial effects in
      the ADT, MLN or LQbATP, since these methods depend on diffusion/extraction of an
      active agent. However, they showed a strong antimicrobial effect in the challenge
      tests as they possess a high absorptive capacity, and are able to bind and
      sequester micro-organisms present. Therefore, it seems recommendable to choose
      several tests to distinguish whether a material conveys an active effect or a
      passive mechanism. In addition, it could be shown that release of silver and its
      antimicrobial efficacy is partially pH-dependent, and that dressings themselves
      affect the pH. It can further be speculated that dressings' effects on pH and
      release of silver ions act synergistically for antimicrobial efficacy. 

PMID- 25578698
TI  - Antibiotic-loaded calcium carbonate/calcium sulfate granules as co-adjuvant for
      bone grafting.
AB  - In this study HERAFILL((r)) granules containing gentamicin was evaluated as a
      bone void filling material once mixed with allograft bone grafts. The efficacy of
      the bone grafts mixed with HERAFILL((r)) was measured by drug release tests and
      bacterial susceptibility using Bacillus subtilis, Staphylococcus epidermidis and
      Staphylococcus aureus. The effect of storage at -80  degrees C on the delivery
      and efficacy of gentamicin from bone grafts mixed with HERAFILL((r)) was also
      investigated. Higher elution of gentamicin was detected in all stored groups (1
      and 6 months) in comparison with non-stored samples. The gentamicin elution
      released from all groups was efficient on reducing S. aureus and S. epidermidis
      CFU. The susceptibility tests using S. aureus showed less resistance of the
      strain after 1 month of the elution storage. That resistance was not observed
      after 6 months of storage. The capacity of bone grafts to act as gentamicin
      carriers has been confirmed in this study. The different granules sizes did not
      interfere in the delivery rate of the antibiotics or in the activity against the
      bacteria. Storage at -80  degrees C does not interfere on the antibiotic
      activity.

PMID- 25578699
TI  - Influence of 3D porous galactose containing PVA/gelatin hydrogel scaffolds on
      three-dimensional spheroidal morphology of hepatocytes.
AB  - Three-dimensional liver scaffolds are temporary framework that mimics native ECM
      architecture and positively influence hepatocyte lodging, proliferation with
      retention of metabolic activities. The aim of the current study is to develop
      galactose containing physical cross-linked polyvinyl alcohol/gelatin (P/G 8:2 and
      9:1) hydrogel scaffolds via freeze/thaw technique. The 8:2 and 9:1 P/G hydrogels
      exhibited comparable pore size and porosity (P > 0.05). The tensile strength of
      the fabricated 8:2 and 9:1 P/G hydrogel scaffolds were found to be in accordance
      with native human liver. Pore interconnectivity of both the P/G hydrogel
      scaffolds was confirmed by scanning electron micrographs and liquid displacement
      method. Further galactose containing hydrogel promoted cell-cell and cell
      hydrogel interaction, aiding cellular aggregation leading to spheroids formation
      compared to void P/G hydrogel by 7 days. Hence, galactose containing P/G hydrogel
      could be more promising substrate as it showed significantly higher cell
      proliferation and albumin secretion for 21 days when compared to non-galactose
      P/G hydrogels (P < 0.05).

PMID- 25578700
TI  - Electrophoretic deposition of mesoporous bioactive glass on glass-ceramic foam
      scaffolds for bone tissue engineering.
AB  - In this work, the coating of 3-D foam-like glass-ceramic scaffolds with a
      bioactive mesoporous glass (MBG) was investigated. The starting scaffolds, based
      on a non-commercial silicate glass, were fabricated by the polymer sponge replica
      technique followed by sintering; then, electrophoretic deposition (EPD) was
      applied to deposit a MBG layer on the scaffold struts. EPD was also compared with
      other techniques (dipping and direct in situ gelation) and it was shown to lead
      to the most promising results. The scaffold pore structure was maintained after
      the MBG coating by EPD, as assessed by SEM and micro-CT. In vitro bioactivity of
      the scaffolds was assessed by immersion in simulated body fluid and subsequent
      evaluation of hydroxyapatite (HA) formation. The deposition of a MBG coating can
      be a smart strategy to impart bioactive properties to the scaffold, allowing the
      formation of nano-structured HA agglomerates within 48 h from immersion, which
      does not occur on uncoated scaffold surfaces. The mechanical properties of the
      scaffold do not vary after the EPD (compressive strength ~19 MPa, fracture energy
      ~1.2 * 10(6) J m(-3)) and suggest the suitability of the prepared highly
      bioactive constructs as bone tissue engineering implants for load-bearing
      applications.

PMID- 25578701
TI  - Hydroxyapatite and fluorapatite coatings on dental screws: effects of blast
      coating process and biological response.
AB  - This paper describes the deposition of hydroxyapatite (HA) and fluorapatite (FA)
      onto titanium dental screws using a novel ambient temperature coating technique
      named CoBlast. The process utilises a coating medium and a blast medium sprayed
      simultaneously at the substrate surface. The blast medium was a sintered apatite
      (sHA) and two particles sizes (<106 and <180 um) were used to assess their
      influence on the coating process. The influence of the coating process on the
      coating composition, coating adhesion, screw morphology and screw microstructure
      was examined. XRD analysis revealed the coating crystallinity was the same as the
      original HA and FA feedstock powders. Examining the screw's morphology, the
      threads of the CoBlasted screws exhibited rounding compared to the unmodified
      screw. This is due to the abrasive nature of the CoBlast process. The degree of
      rounding was more significant for the screws blasted with the 180 um sHA than the
      106 um sHA. The blast media particle size significantly influences the surface
      roughness of both the substrate and coating and the microstructure of the
      substrate. The screws did not exhibit any loss of coating after insertion into a
      model bone material, indicating that the coating was strongly adhered to the
      substrate. There was no statistically significant difference in cell attachment
      and cell morphology on the unmodified substrates compared to the coated
      substrates. In conclusion, the CoBlast process can be used to deposit HA and FA
      onto complex geometries such as dental screws. The choice of blast medium
      particle size influences the screws morphology. The coating process does not
      negatively impact on the cell attachment and morphology in vitro.

PMID- 25578702
TI  - Synthesis and properties of novel water-soluble fullerene-glycine derivatives as
      new materials for cancer therapy.
AB  - Novel water-soluble fullerene-glycine derivatives were synthesized by means of
      simple organic chemistry. They are completely soluble in water, yielding a clear
      brown solution. The products were characterized by fourier transform infrared
      (FTIR), ultraviolet-visible spectroscopy (UV-Vis), (1)H NMR, (13)C NMR,
      thermogravimetric analyses (TGA), and scanning electron microscopy (SEM). The
      assembly behavior of water-soluble fullerene-glycine derivatives was investigated
      by SEM. The results show that the fullerene-glycine derivatives create morphology
      that is sphere-like. The cytotoxicity to cancer cell lines of the fullerene
      glycine derivatives was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide) and flow cytometry. The results show that fullerene
      glycine derivatives exhibit mortality and apoptosis of the cells which increased
      with the increase of fullerene-glycine derivative concentration. The cytotoxicity
      mechanism of fullerene-glycine derivatives was investigated for the first time.
      Novel water-soluble fullerene-glycine derivatives were synthesized by means of
      simple organic chemistry. The products were characterized by FTIR, UV-Vis, (1)H
      NMR, (13)C NMR, TGA, and SEM. The bioactivities of fullerene-glycine derivative
      materials have been tested, and the results show that compared with the fullerene
      complex, the fullerene-glycine derivative materials exhibit mortality and
      apoptosis of the cells which increased with the increase of fullerene-glycine
      derivative concentration. SEM images showed the macrostructure of fullerene
      glycine derivative materials was spheres. 

PMID- 25578703
TI  - The effects of scaffold architecture and fibrin gel addition on tendon cell
      phenotype.
AB  - Development of tissue engineering scaffolds relies on careful selection of pore
      architecture and chemistry of the cellular environment. Repair of skeletal soft
      tissue, such as tendon, is particularly challenging, since these tissues have a
      relatively poor healing response. When removed from their native environment,
      tendon cells (tenocytes) lose their characteristic morphology and the expression
      of phenotypic markers. To stimulate tendon cells to recreate a healthy
      extracellular matrix, both architectural cues and fibrin gels have been used in
      the past, however, their relative effects have not been studied systematically.
      Within this study, a combination of collagen scaffold architecture, axial and
      isotropic, and fibrin gel addition was assessed, using ovine tendon-derived cells
      to determine the optimal strategy for controlling the proliferation and protein
      expression. Scaffold architecture and fibrin gel addition influenced tendon cell
      behavior independently in vitro. Addition of fibrin gel within a scaffold doubled
      cell number and increased matrix production for all architectures studied.
      However, scaffold architecture dictated the type of matrix produced by cells,
      regardless of fibrin addition. Axial scaffolds, mimicking native tendon, promoted
      a mature matrix, with increased tenomodulin, a marker for mature tendon cells,
      and decreased scleraxis, an early transcription factor for connective tissue.
      This study demonstrated that both architectural cues and fibrin gel addition
      alter cell behavior and that the combination of these signals could improve
      clinical performance of current tissue engineering constructs. 

PMID- 25578705
TI  - Effect of phosphorous ion implantation on the mechanical properties and
      bioactivity of hydroxyapatite.
AB  - Hydroxyapatite (HA) has ability of bone-like apatite formation, which consists
      with chemical interaction between the surface of HA and ions included in body
      fluid. Thus, proper surface modification might enhance the function. In the
      present study, the effect of phosphorous ion implantation on mechanical
      properties and bioactivity of HA was investigated. In order to clarify the effect
      of ion implantation dose, ion dose of 1 * 10(12), 1 * 10(13) and 1 * 10(14)
      ions/cm(2) were selected. Mechanical properties and bioactivity were evaluated in
      4-point bending tests and immersion test in simulated body fluid. Bending
      strength was reduced due to ion implantation. The amount of decreasing strength
      was similar regardless of ion implantation dose. Bone-like apatite formation was
      slightly delayed with ion implantation, however, improvement in interfacial
      strength between bone-like apatite layer and the base HA was indicated. From the
      results, the possibility of phosphorous ion implantation for enhancement of
      bioactivity of HA was proved.

PMID- 25578704
TI  - Microstructured zirconia surfaces modulate osteogenic marker genes in human
      primary osteoblasts.
AB  - In dentistry, zirconia has been used since the early 1990s for endodontic posts,
      more recently for implant abutments and frameworks for fixed dental prostheses.
      Zirconia is biocompatible and mechanically strong enough to serve as implant
      material for oral implants. Although several zirconia implant systems are
      available, currently the scientific and clinical data for zirconia implants are
      not sufficient to recommend them for routine clinical use. Here the influence of
      microstructured yttria-stabilized zirconia (YZ) on human primary osteoblast (HOB)
      behavior was determined. YZ surfaces were treated by sandblasting (YZ-S), acid
      etching (YZ-SE) and additionally heat treatment (YZ-SEH). Morphological changes
      of HOB were determined by scanning electron microscopy. Actin cytoskeleton was
      investigated by laser scanning microscopy and analyzed by novel actin
      quantification software. Differentiation of HOB was determined by real time RT
      PCR. Improved mechanical interlocking of primary HOB into the porous
      microstructure of the acid etched and additionally heat treated YZ-surfaces
      correlates with drastically increased osteocalcin (OCN) gene expression. In
      particular, OCN was considerably elevated in primary HOB after 3 days on YZ-SE
      (13-fold) as well as YZ-SEH (12-fold) surfaces. Shorter actin filaments without
      any favored orientation on YZ-SE and YZ-SEH surfaces are associated with higher
      roughness (Ra) values. Topographically modified yttria-stabilized zirconia is a
      likely material for dental implants with cell stimulating properties achieving or
      actually exceeding those of titanium.

PMID- 25578707
TI  - The corrosion resistance of Wiron((r))88 in the presence of S. mutans and S.
      sobrinus bacteria.
AB  - The corrosion resistance of Wiron((r))88, a Ni-Cr-Mo alloy, was evaluated in
      liquid growth media in the absence and presence of the Streptococcus sobrinus and
      Streptococcus mutans strains. Open circuit potential measurements, cyclic
      voltammetry, linear sweep voltammetry, as well as electronic microscopy coupled
      to electron diffraction spectroscopy (SEM/EDS), were the main techniques used in
      this study. It was concluded that the presence of S. sobrinus and S. mutans have
      only a slight effect on the corrosion resistance of the Wiron((r))88 alloy, with
      the S. mutans being slightly more aggressive. For both strains the corrosion
      resistance R p is of the same order (kOmega cm(2)). After 24 h immersion the S.
      sobrinus lead to and R p of 11.02, while the S. mutans lead to of 5.59 kOmega
      cm(2). SEM/EDS studies on the Wiron((r))88 samples, with 24 days of immersion, at
      37  degrees C, have confirmed bio-corrosion of the alloy occurring through the
      dissolution of Ni as Ni(2+) and formation of chromium and molybdenum oxides. The
      bacterial adhesion to the surface is not uniform.

PMID- 25578706
TI  - Characterization and in vitro evaluation of electrospun chitosan/polycaprolactone
      blend fibrous mat for skin tissue engineering.
AB  - The electrospinning technique allows engineering biomimetic scaffolds within
      micro to nanoscale range mimicking natural extracellular matrix (ECM). Chitosan
      (CS) and polycaprolactone (PCL) were dissolved in a modified solvent mixture
      consisting of formic acid and acetone (3:7) and mixed in different weight ratios
      to get chitosan-polycaprolactone [CS-PCL] blend solutions. The CS-PCL blend
      polymer was electrospun in the same solvent system and compared with PCL. The
      physicochemical characterization of the electrospun fibrous mats was done using
      scanning electron microscopy (SEM), Fourier transform infrared spectroscopy
      (FTIR), tensile test, swelling properties, water contact angle (WCA) analysis,
      surface profilometry and thermo gravimetric analysis (TGA). The CS-PCL fibrous
      mat showed decreased hydrophobicity. The CS-PCL mats also showed improved
      swelling property, tensile strength, thermal stability and surface roughness. The
      cytocompatibility of the CS-PCL and PCL fibrous mats were examined using mouse
      fibroblast (L-929) cell line by direct contact and cellular activity with extract
      of materials confirmed non-cytotoxic nature. The potential of CS-PCL and PCL
      fibrous mats as skin tissue engineering scaffolds were assessed by cell adhesion,
      viability, proliferation and actin distribution using human keratinocytes (HaCaT)
      and L-929 cell lines. Results indicate that CS-PCL is a better scaffold for
      attachment and proliferation of keratinocytes and is a potential material for
      skin tissue engineering. 

PMID- 25578708
TI  - Development of an injectable bioactive bone filler cement with hydrogen
      orthophosphate incorporated calcium sulfate.
AB  - Calcium sulfate cement (CSC) has emerged as a potential bone filler material
      mainly because of the possibility of incorporating therapeutic agents. Delivery
      of the cement through a needle or cannula will make it more useful in clinical
      applications. However, it was not possible to make CSC injectable because of the
      inherent lack of viscosity. The present work demonstrates the design development
      of a viscous and fully-injectable CSC by incorporating hydrogen orthophosphate
      ions, which does not hamper the biocompatibility of the material. The effect of
      addition of hydrogen orthophosphate on the rheological properties of the CSC
      paste was studied using a custom made capillary rheometer. The physicochemical
      changes associated with cement setting process were examined using X-ray
      diffraction and Fourier transform infrared spectroscopy and the thermal changes
      were measured through isothermal differential scanning calorimetry.
      Micromorphological features of different compositions were observed in
      environmental scanning electron microscopy and the presence of phosphate ions was
      identified with energy dispersive X-ray spectroscopic analysis and inductively
      coupled plasma-optical emission spectroscopy. The results indicated that HPO4 (2
      ) ions have profound effects on the rheological properties and setting of the CSC
      paste. Significant finding is that the HPO4 (2-) ions are getting substituted in
      the calcium sulfate dihydrate crystals during setting. The variations of setting
      time and compressive strength of the cement with the additive concentration were
      investigated. An optimum concentration of 2.5 % w/w gave a fully-injectable
      cement with clinically relevant setting time (below 20 min) and compressive
      strength (12 MPa). It was possible to inject the optimised cement paste from a
      syringe through an 18-gauge needle with thumb pressure. This cement will be
      useful both as bone filler and as a local drug delivery medium and it allows
      minimally invasive bone defect management.

PMID- 25578709
TI  - Collagen gel formation in the presence of a carbon nanobrush.
AB  - Type I, bovine skin collagen was allowed to gel in the presence of various
      concentrations of a carbon nanotube material covered with a
      polystyrene/polyaniline copolymer, called a carbon nanobrush (CNB). The rate of
      collagen gelation was enhanced by the presence of the CNB in a dose dependent
      manner. The extent of collagen gelation was due to the concentration of collagen
      and not the amount of CNB. Collagen D-periodicity, and average fibril diameter
      were unchanged by the CNB material as seen in transmission electron micrographs.
      Gel tensile strength was reduced by the presence of the CNB in a dose related
      manner. The collagen-CNB mixture may have a role in the repair and reconstruction
      of wounds or degenerated connective tissue.

PMID- 25578710
TI  - One-step formation and sterilization of gellan and hyaluronan nanohydrogels using
      autoclave.
AB  - The sterilization of nanoparticles for biomedical applications is one of the
      challenges that must be faced in the development of nanoparticulate systems.
      Usually, autoclave sterilization cannot be applied because of stability concerns
      when polymeric nanoparticles are involved. This paper describes an innovative
      method which allows to obtain, using a single step autoclave procedure, the
      preparation and, at the same time, the sterilization of self-assembling
      nanohydrogels (NHs) obtained with cholesterol-derivatized gellan and hyaluronic
      acid. Moreover, by using this approach, NHs, while formed in the autoclave, can
      be easily loaded with drugs. The obtained NHs dispersion can be lyophilized in
      the presence of a cryoprotectant, leading to the original NHs after re-dispersion
      in water. 

PMID- 25578711
TI  - Nanomechanical mapping of bone tissue regenerated by magnetic scaffolds.
AB  - Nanoindentation can provide new insights on the maturity stage of regenerating
      bone. The aim of the present study was the evaluation of the nanomechanical
      properties of newly-formed bone tissue at 4 weeks from the implantation of
      permanent magnets and magnetic scaffolds in the trabecular bone of rabbit femoral
      condyles. Three different groups have been investigated: MAG-A (NdFeB magnet +
      apatite/collagen scaffold with magnetic nanoparticles directly nucleated on the
      collagen fibers during scaffold synthesis); MAG-B (NdFeB magnet +
      apatite/collagen scaffold later infiltrated with magnetic nanoparticles) and MAG
      (NdFeB magnet). The mechanical properties of different-maturity bone tissues,
      i.e. newly-formed immature, newly-formed mature and native trabecular bone have
      been evaluated for the three groups. Contingent correlations between elastic
      modulus and hardness of immature, mature and native bone have been examined and
      discussed, as well as the efficacy of the adopted regeneration method in terms of
      "mechanical gap" between newly-formed and native bone tissue. The results showed
      that MAG-B group provided regenerated bone tissue with mechanical properties
      closer to that of native bone compared to MAG-A or MAG groups after 4 weeks from
      implantation. Further, whereas the mechanical properties of newly-formed immature
      and mature bone were found to be fairly good correlated, no correlation was
      detected between immature or mature bone and native bone. The reported results
      evidence the efficacy of nanoindentation tests for the investigation of the
      maturity of newly-formed bone not accessible through conventional analyses.

PMID- 25578712
TI  - PCL-forsterite nanocomposite fibrous membranes for controlled release of
      dexamethasone.
AB  - The well-known treatment of the alveolar bone defects is guided tissue
      regeneration (GTR). Engineered membranes combined with osteo-differentiation
      factors have been offered a promising strategy for GTR application. Recently,
      poly(epsilon-caprolactone) (PCL)-forsterite (PCL-F) nanocomposite fibrous
      membranes have been developed. However, PCL-F membranes could not promote bone
      tissue regeneration. The aim of this research is to encapsulate an osteogenic
      factor [dexamethasone (DEX)] in PCL-F membranes and evaluate the effects of
      forsterite nanopowder (particle size = 25-45 nm) and fiber organization on DEX
      delivery for GTR application. The hypothesis is that the release kinetic and
      profile of DEX could be controlled through variation of forsterite content (0, 5
      and 10 wt%) and fiber arrangement (aligned and random). Results demonstrated
      while DEX release was sustained over a period of 4 weeks, its kinetic was
      governed by the membrane architecture and composition. For example, aligned PCL-F
      nanocomposite fibrous membrane consisting of 10 %(w/v) forsterite nanopowder
      exhibited the least initial burst release (13 % release in the first 12 h) and
      allowed sustained release of DEX. Additionally, forsterite nanopowder inclusion
      changed the kinetic of DEX release from Fickian diffusion to an anomalous
      transport. The bioactivity of released DEX was estimated using culturing the stem
      cells from human exfoliated deciduous teeth (SHED) on the membranes. Results
      demonstrated that proliferation and osteogenic differentiation of SHED could be
      governed by DEX release process. While DEX release from the membranes decreased
      SHED proliferation, stimulated the matrix mineralization. Our finding indicated
      that aligned PCL-F/DEX membrane could be used as a carrier for the sustained
      release of drugs relevant for GTR trophy.

PMID- 25578713
TI  - Dual growth factor-loaded in situ gel-forming bulking agent: passive and
      bioactive effects for the treatment of urinary incontinence.
AB  - Stress urinary incontinence (SUI) is one of the major medical problems for adult
      females and has a devastating effect on their quality of life. The major cause of
      the development of the SUI is dysfunction of the urethral supporting tissues as a
      result of aging and childbirth. In this study, in situ gel-forming bulking agent
      loaded with dual growth factors, nerve growth factor (NGF) and basic fibroblast
      growth factor (bFGF), was fabricated. The bulking agent consisted of three
      components; (i) polycaprolactone (PCL) beads, (ii) bFGF-loaded nanogels, and
      (iii) NGF-loaded in situ gel forming solution. The bulking agent can provide an
      initial passive bulking effect (from the PCL beads) and regenerate malfunctioning
      tissues around the urethra (from the sequential and continuous release of growth
      factors from the hydrogel) for the effective treatment of SUI. The PCL beads were
      located stably at the applied urethra site (urinary incontinent SD rat) without
      migration to provide a passive bulking effect. The sequential release of the
      growth factors (NGF within a week and bFGF for more than 4 weeks) from the
      bulking agent provided regeneration of damaged nerve and smooth muscle, and thus
      enhanced biological function around the urethra. From the findings, we suggest
      that dual growth factor (NGF and bFGF)-loaded in situ gel-forming bulking agent
      may be a promising injectable bioactive system for the treatment for SUI.

PMID- 25578714
TI  - Structure and properties of PLLA/beta-TCP nanocomposite scaffolds for bone tissue
      engineering.
AB  - One of the key components of tissue engineering is a scaffold with suitable
      morphology, outstanding mechanical properties, and favorable biocompatibility. In
      this study, beta-tricalcium phosphate (beta-TCP) nanoparticles were synthesized
      and incorporated with poly(L-lactic acid) (PLLA) to fabricate nanocomposite
      scaffolds by the thermally induced phase separation method. The PLLA/beta-TCP
      nanocomposite scaffolds showed a continuous nanofibrous PLLA matrix with strut
      diameters of 100-750 nm, interconnected micropores with pore diameters in the
      range of 0.5-10 MUm, and high porosity (>92 %). beta-TCP nanoparticles were
      homogeneously dispersed in the PLLA matrix, which significantly improved the
      compressive modulus and protein adsorption capacity. The prepared nanocomposite
      scaffolds provided a suitable microenvironment for osteoblast attachment and
      proliferation, demonstrating the potential of the PLLA/beta-TCP nanocomposite
      scaffolds in bone tissue engineering applications.

PMID- 25578715
TI  - Mechanical characterization of electrospun gelatin scaffolds cross-linked by
      glucose.
AB  - Nanofibrous gelatin scaffolds were prepared by electrospinning from aqueous
      acetic acid and cross-linked thermally by glucose. The effect of the amount of
      glucose used as cross-linking agent on the mechanical properties of gelatin
      fibres was studied in this paper. The elastic modulus of gelatin fibres cross
      linked by glucose was determined by modelling the behaviour of the meshes during
      tensile test. The model draws connections between the elastic moduli of a fibrous
      mesh and the fibre material and allows evaluation of elastic modulus of the fibre
      material. It was found that cross-linking by glucose increases the elastic
      modulus of gelatin fibres from 0.3 GPa at 0 % glucose content to 1.1 GPa at 15 %
      glucose content. This makes fibrous gelatin scaffolds cross-linked by glucose a
      promising material for biomedical applications.

PMID- 25578716
TI  - Improving the finite element model accuracy of tissue engineering scaffolds
      produced by selective laser sintering.
AB  - In bone tissue engineering, both geometrical and mechanical properties of a
      scaffold play a major part in the success of the treatment. The mechanical
      stresses and strains that act on cells on a scaffold in a physiological
      environment are a determining factor on the subsequent tissue formation.
      Computational models are often used to simulate the effect of changes of internal
      architectures and external loads applied to the scaffold in order to optimise the
      scaffold geometry for the prospective implantation site. Finite element analysis
      (FEA) based on computer models of the scaffold is a common technique, but would
      not take into account actual inaccuracies due to the manufacturing process. Image
      based FEA using CT scans of fabricated scaffolds can provide a more accurate
      analysis of the scaffold, and was used in this work in order to accurately
      simulate and predict the mechanical performance of bone tissue engineering
      scaffolds, fabricated using selective laser sintering (SLS), with a view to
      generating a methodology that could be used to optimise scaffold design. The
      present work revealed that an approach that assumes isotropic properties of SLS
      fabricated scaffolds will lead to inaccurate predictions of the FE model.
      However, a dependency of the grey value of the CT scans and the mechanical
      properties was discovered, which may ultimately lead to accurate FE models
      without the need of experimental validation.

PMID- 25578717
TI  - On the road to synthetic life: the minimal cell and genome-scale engineering.
AB  - Synthetic biology employs rational engineering principles to build biological
      systems from the libraries of standard, well characterized biological parts.
      Biological systems designed and built by synthetic biologists fulfill a plethora
      of useful purposes, ranging from better healthcare and energy production to
      biomanufacturing. Recent advancements in the synthesis, assembly and "booting-up"
      of synthetic genomes and in low and high-throughput genome engineering have paved
      the way for engineering on the genome-wide scale. One of the key goals of genome
      engineering is the construction of minimal genomes consisting solely of essential
      genes (genes indispensable for survival of living organisms). Besides serving as
      a toolbox to understand the universal principles of life, the cell encoded by
      minimal genome could be used to build a stringently controlled "cell factory"
      with a desired phenotype. This review provides an update on recent advances in
      the genome-scale engineering with particular emphasis on the engineering of
      minimal genomes. Furthermore, it presents an ongoing discussion to the scientific
      community for better suitability of minimal or robust cells for industrial
      applications. 

PMID- 25578718
TI  - Toward the development of smart and low cost point-of-care biosensors based on
      screen printed electrodes.
AB  - Screen printing technology provides a cheap and easy means to fabricate
      disposable electrochemical devices in bulk quantities which are used for rapid,
      low-cost, on-site, real-time and recurrent industrial, pharmaceutical or
      environmental analyses. Recent developments in micro-fabrication and nano
      characterization made it possible to screen print reproducible feature on
      materials including plastics, ceramics and metals. The processed features forms
      screen-printed disposable biochip (SPDB) upon the application of suitable bio
      chemical recognition receptors following appropriate methods. Adequacy of
      biological and non-biological materials is the key to successful biochip
      development. We can further improve recognition ability of SPDBs by adopting new
      screen printed electrode (SPE) configurations. This review covers screen-printing
      theory with special emphasis on the technical impacts of SPE architectures,
      surface treatments, operational stability and signal sensitivity. The application
      of SPE in different areas has also been summarized. The article aims to highlight
      the state-of-the-art of SPDB at the laboratory scale to enable us in envisaging
      the deployment of emerging SPDB technology on the commercial scale. 

PMID- 25578726
TI  - Stem-cell-like properties and epithelial plasticity arise as stable traits after
      transient Twist1 activation.
AB  - Master regulators of the epithelial-mesenchymal transition such as Twist1 and
      Snail1 have been implicated in invasiveness and the generation of cancer stem
      cells, but their persistent activity inhibits stem-cell-like properties and the
      outgrowth of disseminated cancer cells into macroscopic metastases. Here, we show
      that Twist1 activation primes a subset of mammary epithelial cells for stem-cell
      like properties, which only emerge and stably persist following Twist1
      deactivation. Consequently, when cells undergo a mesenchymal-epithelial
      transition (MET), they do not return to their original epithelial cell state,
      evidenced by acquisition of invasive growth behavior and a distinct gene
      expression profile. These data provide an explanation for how transient Twist1
      activation may promote all steps of the metastatic cascade; i.e., invasion,
      dissemination, and metastatic outgrowth at distant sites.

PMID- 25578727
TI  - The deubiquitinating enzyme USP24 is a regulator of the UV damage response.
AB  - Regulation of p53 by ubiquitination and deubiquitination is important for its
      function. In this study, we demonstrate that USP24 deubiquitinates p53 in human
      cells. Functional USP24 is required for p53 stabilization, and p53
      destabilization in USP24-depleted cells can be corrected by the forced expression
      of USP24. We show that USP24 depletion renders cells resistant to apoptosis after
      UV irradiation, consistent with the requirement of USP24 for p53 stabilization
      and PUMA activation in vivo. Additionally, purified USP24 protein is able to
      cleave ubiquitinated p53 in vitro. Importantly, cells with USP24 depletion
      exhibited significantly elevated mutation rates at the endogenous HPRT locus,
      implying an important role for USP24 in maintaining genome stability. Our data
      reveal that the USP24 deubiquitinase regulates the DNA damage response by
      directly targeting the p53 tumor suppressor. 

PMID- 25578728
TI  - The human nuclear exosome targeting complex is loaded onto newly synthesized RNA
      to direct early ribonucleolysis.
AB  - The RNA exosome complex constitutes the major nuclear eukaryotic 3'-5'
      exonuclease. Outside of nucleoli, the human nucleoplasmic exosome is directed to
      some of its substrates by the nuclear exosome targeting (NEXT) complex. How NEXT
      targets RNA has remained elusive. Using an in vivo crosslinking approach, we
      report global RNA binding sites of RBM7, a key component of NEXT. RBM7 associates
      broadly with RNA polymerase II-derived RNA, including pre-mRNA and short-lived
      exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs
      (eRNAs), and 3'-extended products from snRNA and replication-dependent histone
      genes. Within pre-mRNA, RBM7 accumulates at the 3' ends of introns, and pulse
      labeling experiments demonstrate that RBM7/NEXT defines an early exosome
      targeting pathway for 3'-extended snoRNAs derived from such introns. We propose
      that RBM7 is generally loaded onto newly synthesized RNA to accommodate exosome
      action in case of available unprotected RNA 3' ends.

PMID- 25578729
TI  - Nucleosome contact triggers conformational changes of Rpd3S driving high-affinity
      H3K36me nucleosome engagement.
AB  - The Rpd3S histone deacetylase complex utilizes two subunits, Eaf3 and Rco1, to
      recognize nucleosomes methylated at H3K36 (H3K36me) with high affinity and strong
      specificity. However, the chromobarrel domain of Eaf3 (CHD) that is responsible
      for H3K36me recognition only binds weakly and with little specificity to histone
      peptides. Here, using deuterium exchange mass spectrometry (DXMS), we detected
      conformational changes of Rpd3S upon its contact with chromatin. Interestingly,
      we found that the Sin3-interacting domain of Rco1 (SID) allosterically stimulates
      preferential binding of Eaf3 to H3K36-methylated peptides. This activation is
      tightly regulated by an autoinhibitory mechanism to ensure optimal multivalent
      engagement of Rpd3S with nucleosomes. Lastly, we identified mutations at the
      interface between SID and Eaf3 that do not disrupt complex integrity but severely
      compromise Rpd3S functions in vitro and in vivo, suggesting that the nucleosome
      induced conformational changes are essential for chromatin recognition.

PMID- 25578730
TI  - Nucleosome assembly dynamics involve spontaneous fluctuations in the handedness
      of tetrasomes.
AB  - DNA wrapping around histone octamers generates nucleosomes, the basic compaction
      unit of eukaryotic chromatin. Nucleosome stability is carefully tuned to maintain
      DNA accessibility in transcription, replication, and repair. Using freely
      orbiting magnetic tweezers, which measure the twist and length of single DNA
      molecules, we monitor the real-time loading of tetramers or complete histone
      octamers onto DNA by Nucleosome Assembly Protein-1 (NAP1). Remarkably, we find
      that tetrasomes exhibit spontaneous flipping between a preferentially occupied
      left-handed state (DeltaLk = -0.73) and a right-handed state (DeltaLk = +1.0),
      separated by a free energy difference of 2.3 kBT (1.5 kcal/mol). This flipping
      occurs without concomitant changes in DNA end-to-end length. The application of
      weak positive torque converts left-handed tetrasomes into right-handed
      tetrasomes, whereas nucleosomes display more gradual conformational changes. Our
      findings reveal unexpected dynamical rearrangements of the nucleosomal structure,
      suggesting that chromatin can serve as a "twist reservoir," offering a
      mechanistic explanation for the regulation of DNA supercoiling in chromatin.

PMID- 25578731
TI  - RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage.
AB  - Ubiquitination regulates numerous cellular processes by generating a versatile
      communication system based on eight structurally and functionally different
      chains linked through distinct residues. Except for K48 and K63, the biological
      relevance of different linkages is largely unclear. Here, we show that RNF168
      ubiquitin ligase promotes noncanonical K27-linked ubiquitination both in vivo and
      in vitro. We demonstrate that residue K27 of ubiquitin (UbK27) is required for
      RNF168-dependent chromatin ubiquitination, by targeting histones H2A/H2A.X, and
      that it is the major ubiquitin-based modification marking chromatin upon DNA
      damage. Indeed, UbK27 is strictly required for the proper activation of the DNA
      damage response (DDR) and is directly recognized by crucial DDR mediators, namely
      53BP1, Rap80, RNF168, and RNF169. Mutation of UbK27 has dramatic consequences on
      DDR activation, preventing the recruitment of 53BP1 and BRCA1 to DDR foci.
      Similarly to the DDR, atypical ubiquitin chains could play unanticipated roles in
      other crucial ubiquitin-mediated biological processes.

PMID- 25578732
TI  - Adipose fatty acid oxidation is required for thermogenesis and potentiates
      oxidative stress-induced inflammation.
AB  - To understand the contribution of adipose tissue fatty acid oxidation to whole
      body metabolism, we generated mice with an adipose-specific knockout of carnitine
      palmitoyltransferase 2 (CPT2(A-/-)), an obligate step in mitochondrial long-chain
      fatty acid oxidation. CPT2(A-/-) mice became hypothermic after an acute cold
      challenge, and CPT2(A-/-) brown adipose tissue (BAT) failed to upregulate
      thermogenic genes in response to agonist-induced stimulation. The adipose
      specific loss of CPT2 resulted in diet-dependent changes in adiposity but did not
      result in changes in body weight on low- or high-fat diets. Additionally, CPT2(A
      /-) mice had suppressed high-fat diet-induced oxidative stress and inflammation
      in visceral white adipose tissue (WAT); however, high-fat diet-induced glucose
      intolerance was not improved. These data show that fatty acid oxidation is
      required for cold-induced thermogenesis in BAT and high-fat diet-induced
      oxidative stress and inflammation in WAT. 

PMID- 25578733
TI  - Homeostatic control of memory cell progenitors in the natural killer cell
      lineage.
AB  - Recent studies have demonstrated that natural killer (NK) cells are able to
      undergo clonal expansion and contraction and to generate self-renewing memory
      cells after infection with mouse cytomegalovirus (MCMV). It is unclear whether
      all or only certain subsets preferentially contribute to the generation of memory
      NK cells. Here, we show that memory NK cells predominantly arise from killer cell
      lectin-like receptor G1 (KLRG1)-negative NK cell progenitors, whereas KLRG1
      positive NK cells have limited capacity for expansion during infection with MCMV.
      Unexpectedly, the frequency of KLRG1-positive NK cells is significantly affected
      by the presence of T cells in the host and potentially by the host microbiota.
      Our findings demonstrate that excessive availability of interleukin (IL)-15 may
      erode the pool of memory progenitors, resulting in the decreased efficiency of
      memory generation in the NK cell lineage.

PMID- 25578734
TI  - Synthesis, characterization and antitumor activities of some steroidal
      derivatives with side chain of 17-hydrazone aromatic heterocycle.
AB  - Here a series of dehydroepiandrosterone-17-hydrazone and estrone-17-hydrazone
      derivatives possessing various aromatic heterocycle structures in 17-side chain
      of their steroidal nucleus were synthesized and their structures were evaluated.
      The antiproliferative activity of synthesized compounds against some cancer cells
      was investigated. The results have demonstrated that some dehydroepiandrosterone
      17-hydrazone derivatives show distinct antiproliferative activity against some
      cancer cells through inducing cancer cell apoptosis, and compound 8 with a
      quinoline structure in 17-side chain displays excellent antiproliferative
      activity in vitro against SGC 7901 cancer cell (human gastric carcinoma) with an
      IC50 value of 1 MUM. In addition, estrone-17-hydrazone derivatives having a key
      feature of indole group in the structure showed a special obvious cytotoxicity
      against HeLa cells, but almost inactive against other cells. The information
      obtained from the studies is valuable for the design of novel steroidal
      chemotherapeutic drugs.

PMID- 25578735
TI  - Cholesterol metabolite cholestane-3beta,5alpha,6beta-triol suppresses epileptic
      seizures by negative modulation of voltage-gated sodium channels.
AB  - Imbalance of excitation and inhibition in neurons is implicated in the
      pathogenesis of epilepsy. Voltage-gated sodium channels, which play a vital role
      in regulating neuronal excitability, are one of the major targets for developing
      anti-epileptic drugs. Here we provide evidence that cholestane-3beta,5alpha,6beta
      triol (triol), a major metabolic oxysterol of cholesterol, is an effective state
      dependent negative sodium channels modulator. Triol reduced Na(+) current density
      in a concentration-dependent manner. 10 MUM triol shifted steady-state/fast/slow
      inactivation curves of sodium channels toward the hyperpolarizing direction.
      Additionally, triol reduced voltage-gated sodium currents in a voltage- and
      frequency-dependent manner. In a kainic acid-induced seizures mouse model, triol
      (25 mg/kg) significantly increased the latency of seizure onset and attenuated
      seizure severity. Our findings provide novel insights for understanding the
      modulatory role of a small molecular oxysterol on voltage-gated sodium channels
      and suggest triol may represent a novel and promising candidate for epilepsy
      intervention.

PMID- 25578736
TI  - The effect of exogenous 24-epibrassinolide on the ecdysteroid content in the
      leaves of Spinacia oleracea L.
AB  - The aim of this study was to show whether/how the application of exogenous 24
      epibrassinolide can affect the content of ecdysteroids in spinach leaves.
      Brassinosteroids and ecdysteroids, structurally related phytosterols, show effect
      on a range of processes in plants. Brassinosteroids increase biomass yield in
      some species, photosynthesis and resistance to stress, and ecdysteroids show
      effect on proteins responsible for binding of CO2 or water cleavage. The mutual
      interaction of these sterols in plants is unclear. The UPLC-(+)ESI-MS/MS analyses
      of extracts of treated and untreated spinach (Spinacia oleracea L.) leaves show
      that the application of exogenous 24-epibrassinolide does influence the
      ecdysteroid content in plant tissues. The response differs for the major
      ecdysteroids and also differs from that for the minor ones and is dependent on
      the developmental stage of the leaves within the same plant or the 24
      epibrassinolide concentration applied. 

PMID- 25578737
TI  - Design and synthesis of new dihydrotestosterone derivative with positive
      inotropic activity.
AB  - There are several reports which indicate that some steroid derivatives have
      inotropic activity; nevertheless, the cellular site and mechanism of action of
      steroid derivatives at cardiovascular level is very confusing. In order, to
      clarify these phenomena in this study, two dihydrotestosterone derivatives
      (compounds 5 and 10) were synthesized with the objective of to evaluate its
      biological activity on left ventricular pressure and characterize their molecular
      mechanism. In the first stage, the Langendorff technique was used to measure
      changes on perfusion pressure and coronary resistance in an isolated rat heart
      model in absence or presence of the steroid derivatives. Additionally, to
      characterize the molecular mechanism involved in the inotropic activity induced
      by the compound 5 was evaluated by measuring left ventricular pressure in absence
      or presence of following compounds; nifedipine, flutamide, indomethacin,
      prazosin, isoproterenol, propranolol and metoprolol. The results showed that the
      compound 5 significantly increased the perfusion pressure and coronary resistance
      in comparison with dihydrotestosterone, compound 10 and the control conditions.
      Other data indicate that 5 increase left ventricular pressure in a dose-dependent
      manner (0.001-100 nM); nevertheless, this phenomenon was significantly inhibited
      only by propranolol or metoprolol at a dose of 1 nM. These data suggest that
      positive inotropic activity induced by the compound 5 is through beta1-adrenergic
      receptor however, this effect was independent of cAMP levels. This phenomenon is
      a particularly interesting because the positive inotropic activity induced by
      this steroid derivative involves a molecular mechanism different in comparison
      with other positive inotropic drugs.

PMID- 25578740
TI  - Drinking water microbiology--from measurement to management.
AB  - New microbial tools enable detailed quantification and characterization of
      complex drinking water (DW) microbiomes. Many opportunities exist from source to
      tap to apply this knowledge toward management of the microbiology. This requires
      consideration of the microbiome continuum across all phases harboring microbes
      (planktonic cells, biofilms, and cells attached to loose deposits) and across all
      stages (source, treatment, distribution, and premise). Biofilters can be
      optimized toward specific compound removal and can seed the distribution network
      (DN) with beneficial bacteria. Disinfection aggressively controls the microbiome,
      but may select for unwanted bacteria. Within premise plumbing, dramatic changes
      occur with unavoidable stagnation and pipe material influence. To supply safe DW
      sustainably, it is imperative that the field progress from characterization
      toward management of the DW microbiome. 

PMID- 25578741
TI  - Radiologic and Histopathologic Features of Calcifying Pseudoneoplasm of the
      Neural Axis.
AB  - AIM: To describe the radiologic and corresponding histopathologic features of
      calcifying pseudoneoplasms of the neural axis. METHODS: Two cases of calcifying
      pseudoneoplasm of the neural axis were retrospectively reviewed. The first case
      was documented in a 64-year-old woman, who presented with lower back pain with
      radiation to her left leg. The second case was documented in a 70-year-old man,
      who presented with headaches. Medical records, radiologic and histologic
      findings, and related literature were reviewed. RESULTS: In the first case,
      imaging of the lumbar spine revealed a 3.8 * 2.2-cm calcified lesion at the level
      of vertebrae L5 and S1. A subsequent excision exposed an extradural lesion at L5.
      Histopathologic examination showed amorphous and granular calcifying material
      with occasional fibrohistiocytic and giant cell reaction, consistent with
      calcifying pseudoneoplasm of the neural axis. In the second case, imaging of the
      head revealed a 2.4 * 2.6-cm well-circumscribed, lobulated, calcified lesion
      within the basal frontal lobe. Subsequent resection exposed an intradural mass
      with a nodular arrangement of amorphous and granular calcifying material
      associated with fibrohistiocytic and giant cell reaction. Both patients had a
      favorable postoperative course and failed to show any clinical or radiologic sign
      of recurrence. CONCLUSION: Calcifying pseudoneoplasm of the neural axis is an
      uncommon condition with an excellent prognosis but is often misdiagnosed due to
      its nonspecific clinical presentation and varied findings on radiology.

PMID- 25578738
TI  - Antinuclear antibody-negative systemic sclerosis.
AB  - OBJECTIVE: To examine the demographic and clinical characteristics of systemic
      sclerosis (SSc) patients without antinuclear antibodies (ANA) compared to ANA
      positive patients. METHODS: SSc patients enrolled in the Scleroderma Family
      Registry and DNA Repository were included. Relevant demographic and clinical data
      were entered by participating sites or obtained by chart review. ANA and SSc
      related antibodies were determined in all investigated patients using
      commercially available kits at our laboratories. RESULTS: This study included
      3249 patients, of whom 208 (6.4%) were ANA negative. The proportion of male
      patients was higher in the ANA-negative group (OR = 1.65; p = 0.008). ANA
      negative patients experienced less vasculopathic manifestations of SSc. The
      percent predicted diffusing capacity of carbon monoxide (DLCO) was higher in ANA
      negative patients (p = 0.03). Pulmonary arterial hypertension (PAH) per right
      heart catheterization was less common in the ANA-negative group (OR = 0.28; p =
      0.03). Furthermore, patients with negative ANA had a lower prevalence of
      telangiectasias and digital ulcers/pits (OR = 0.59, p = 0.03 and OR = 0.38, p =
      0.01, respectively). Although diffuse cutaneous involvement was more common, the
      modified Rodnan Skin Score (mRSS) was lower in the ANA-negative group (2.4 points
      lower, p = 0.05). Furthermore, they experienced more malabsorption (p = 0.05).
      There was no difference in the frequency of pulmonary fibrosis or scleroderma
      renal crisis. All-cause mortality was not different between the 2 groups (p =
      0.28). CONCLUSIONS: In conclusion, the results of this study suggest that SSc
      patients who are ANA negative constitute a distinct subset of SSc with less
      vasculopathy (less PAH, digital ulcers, and fewer telangiectasias), a greater
      proportion of males, and possibly, more frequent lower gastrointestinal
      involvement.

PMID- 25578739
TI  - Systematic review and meta-analysis of the survival outcomes of first-line
      treatment options in high-risk prostate cancer.
AB  - Prostate cancer (PCa) is the most common non-dermatologic cancer in the western
      countries in western countries. High-risk PCa accounts for 15% of the diagnosed
      cases. In this study, we compare the long-term survival outcomes of radical
      prostatectomy (RP), radiation therapy (RT), brachytherapy (BT), androgen-
      deprivation therapy (ADT), and watchful waiting (WW) in high-risk prostate cancer
      (PCa). Overall, RP/(RT plus ADT) gave the best survival outcome in patients with
      high-risk PCa, whereas ADT/WW had the worst outcome. The overall priority for
      treatment strategy could be ranked as follows: RP/(RT plus ADT), RT, and ADT/WW.
      RP had significant better overall survival (OS) than RT or BT, and RP had
      significant lower cancer-specific mortality (CSM) than RT (0.51 [95% CI 0.30
      0.73], P<0.001). ADT improved the cancer-specific survival (CSS) of RP based on a
      case-controlled study; added ADT to RT failed to challenge the position of RP but
      could improve the outcome of RT. In conclusions,RP/(RT plus adjuvant ADT) could
      both be used for the first-line therapy of high-risk PCa. When encountering an
      individual patient, urologists should consider various factors like tumors
      themselves, preferences of individuals, and so on. 

PMID- 25578742
TI  - Spontaneous T1-Hyperintensity Within an Ovarian Lesion: Spectrum of Diagnoses.
AB  - Whenever elevated signal intensity is displayed at magnetic resonance imaging
      (MRI) within an ovarian lesion on unenhanced T1-weighted sequences, some specific
      diagnoses should be considered because only 3 main components may be responsible
      for this T1-hyperintensity at MRI: fat, blood products, and proteinaceous or
      mucinous material. The associated clinical data and concomitant use of T2
      weighted sequences and fat-saturation techniques is mandatory to make this tissue
      characterization possible. The goal of this pictorial review is to provide a
      simple radiologic reasoning and the differential diagnoses to consider in the
      presence of spontaneous elevated signal intensity on T1-weighted sequences within
      a cystic or solid ovarian tumour. 

PMID- 25578743
TI  - Assimilating endocrine anatomy through simulation: a pre-emptive strike!
AB  - BACKGROUND: We sought to determine if endocrine anatomy could be learned with the
      aid of a hands-on, low-cost, low-fidelity surgical simulation curriculum and pre
      emptive 60-second YouTube video clip. METHODS: A 3-hour endocrine surgery
      simulation session was held on back-to-back Fridays. A video clip was made
      available to the 2nd group of learners. A comprehensive 40-point test was
      administered before (pre-test) and after (post-test) the sessions. RESULTS:
      General surgery interns (n = 26) participated. The video was viewed 19 times by
      80% (12 of 15) of interns with access. Viewers outperformed nonviewers on
      subsequent post-testing (mean [SD], 29.7 [1.3] vs 24.4 [1.6]; P = .015). Mean
      scores on the anatomy section of the post-test were higher among viewers than
      nonviewers (mean [SD] 14.2 [.9] vs 10.3 [1.0]; P = .012). CONCLUSIONS: Low-cost
      simulation models can be used to teach endocrine anatomy. Pre-emptive viewing of
      a 60-second video may have been a key factor resulting in higher post-test scores
      compared with controls, suggesting that the video intervention improved the
      educational effectiveness of the session.

PMID- 25578745
TI  - Oxidation of a model alkane aerosol by OH radical: the emergent nature of
      reactive uptake.
AB  - An accurate description of the evolution of organic aerosol in the Earth's
      atmosphere is essential for climate models. However, the complexity of multiphase
      chemical and physical transformations has been challenging to describe at the
      level required to predict aerosol lifetimes and changes in chemical composition.
      In this work a model is presented that reproduces experimental data for the early
      stages of oxidative aging of squalane aerosol by hydroxyl radical (OH), a process
      governed by reactive uptake of gas phase species onto the particle surface.
      Simulations coupling free radical reactions and Fickian diffusion are used to
      elucidate how the measured uptake coefficient reflects the elementary steps of
      sticking of OH to the aerosol as a result of a gas-surface collision, followed by
      very rapid abstraction of hydrogen and subsequent free radical reactions. It is
      found that the uptake coefficient is not equivalent to a sticking coefficient or
      an accommodation coefficient: it is an intrinsically emergent process that
      depends upon particle size, viscosity, and OH concentration. An expression is
      derived to examine how these factors control reactive uptake over a broad range
      of atmospheric and laboratory conditions, and is shown to be consistent with
      simulation results. Well-mixed, liquid behavior is found to depend on the
      reaction conditions in addition to the nature of the organic species in the
      aerosol particle. 

PMID- 25578744
TI  - Early effects of bougie size on sleeve gastrectomy outcome.
AB  - BACKGROUND: When performing sleeve gastrectomy, a bougie (32 to 60 French) is
      used. We evaluated 2 different bougie sizes on early postoperative outcomes and
      long-term weight loss. METHODS: A 1-year prospective study was conducted on
      patients undergoing sleeve gastrectomy. In the first 6 months, patients had 32
      French bougies (Group 1); in the second 6 months, they had 36-French bougies
      (Group 2). RESULTS: We evaluated 131 patients. No intraoperative complications or
      mortality occurred. Postoperatively, Group 1 (n = 72) had a longer hospital stay
      (1.6 +/- .8 vs 1.3 +/- .5 days, P = .04) and used more Ondansetron for nausea
      than Group 2 (n = 59) (6.7 +/- 8.0 vs 5.3 +/- 4.5 mg, P = .2, respectively). Ten
      (14%) patients in Group 1 returned to the emergency department compared with 5
      (9%) in Group 2. One-year percent excess weight loss was similar (73.0 +/- 20.6%
      vs 71.1 +/- 20.9%, P = .73, respectively). CONCLUSIONS: The smaller bougie
      resulted in a longer hospital stay, with tendency toward increased nausea, more
      emergency department visits, and readmissions. Long-term weight loss was not
      affected.

PMID- 25578746
TI  - Dendrimer generational nomenclature: the need to harmonize.

PMID- 25578758
TI  - Effect of carnosic acid, quercetin and alpha-tocopherol on lipid and protein
      oxidation in an in vitro simulated gastric digestion model.
AB  - Carnosic acid, quercetin and alpha-tocopherol are well-known antioxidants in many
      biological systems. However, their antioxidative effect during food digestion
      against lipid and protein oxidation is not well known. Therefore, in this study,
      an in vitro simulated gastric digestion model was used to investigate their
      stability during gastrointestinal conditions and their antioxidative properties
      during low pH digestion. In general, the stability of the antioxidants in the
      different steps of digestion was in the order of alpha-tocopherol > quercetin >
      carnosic acid. Salivary components, as well as the acidity of the gastric juice,
      were responsible for the reduction in antioxidants. Both alpha-tocopherol and
      quercetin were able to lower lipid oxidation during digestion, while the effect
      on protein oxidation was not clear. In contrast, carnosic acid did not have any
      effect on lipid oxidation and tended to stimulate protein oxidation. This study
      clearly demonstrated that the environmental conditions are of major importance to
      the properties of antioxidant compounds.

PMID- 25578759
TI  - Effect of dietary fiber on circulating C-reactive protein in overweight and obese
      adults: a meta-analysis of randomized controlled trials.
AB  - Previous studies suggested that dietary fiber intake may have a lowing effect on
      circulating C-reactive protein (CRP) level, a sensitive marker of inflammation,
      in overweight/obese adults with inconsistent results. A literature search was
      performed in April 2014 for related randomized controlled trials (RCTs) and meta
      analysis was conducted. Meta-analysis including 14 RCTs showed that intervention
      with dietary fiber or fiber-rich food, compared with control, produced a slight,
      but significant reduction of 0.37 mg/L (95% CI -0.74, 0) in circulating CRP level
      among this population. Subgroup analyses showed that such a significant reduction
      was only observed after combining studies where the total fiber intake was 8 g/d
      higher in the intervention group than in the control group. No obvious
      heterogeneity and publication bias were found in the meta-analysis. In
      conclusion, this meta-analysis provides evidence that dietary fiber or food
      naturally rich in fiber has beneficial effects on circulating CRP level in
      overweight/obese adults.

PMID- 25578760
TI  - Biotechnological innovations for table olives.
AB  - The production of table olives is based on a relatively simple flow chart,
      including debittering and lactic fermentation. Producers' demand for innovation
      was the background to design and test some innovative and alternative approaches,
      i.e. the selection of suitable starter cultures (both lactic acid bacteria and
      yeasts), the production of functional olives inoculated with probiotic strains,
      the use of bioremediation (i.e. degradation of oleuropein by bacteria or yeasts),
      as well as the inoculation of functional starter cultures with a strong
      biopreservative effect. This article reports a brief description of the most
      important innovations, with a special focus on the role of traditional and
      innovative starter cultures. 

PMID- 25578761
TI  - Effect of pH and metal ions on DPPH radical scavenging activity of tea.
AB  - The 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay is commonly applied for the
      estimation of antioxidant activity of plant extracts. This article discusses the
      effect of a sample pH and the presence of metal ions on the results obtained
      using DPPH method for several tea infusions. Higher radical quenching was
      observed in less acidic media. The impact of metal ions depends of the types of
      metal ion and its concentration. Quercetin and epigallocatechin gallate were less
      efficient in the reaction with DPPH in the presence of Al(III). Desalting process
      using cation-exchange resin Dowex 50Wx8 decreased the content of metal ions in
      all studied tea infusions. The DPPH scavenging activity of the effluents after
      this process were higher than those of the primary extracts and this may be
      related to the actual antioxidant capacity of these samples.

PMID- 25578762
TI  - Combined effects of added beta glucan and black tea in breads on starch
      functionality.
AB  - Bread and tea are usually consumed separately, but there may be different food
      matrix interactions and changes in starch characteristics when they are combined
      in bread. This study developed breads (white bread, WF; black tea, BT; beta
      glucan, betaG; beta glucan plus black tea, betaGBT) and determined their starch
      functionalities. Breads were developed using a standard baking recipe and
      determined their starch characteristics. There was no significant difference in
      starch hydrolysis between BT and WF but betaGBT reduced early (10 min) starch
      hydrolysis compared with betaG. The starch granules in betaG and betaGBT were
      elliptical and closely packed together. These results suggest that the addition
      of beta glucan and black tea to bread preserved the elliptical starch granules
      and lowered short-term starch hydrolysis.

PMID- 25578763
TI  - Phytochemical composition and antioxidant capacity of whole wheat products.
AB  - Whole wheat contains an array of phytochemicals. We quantified alkylresorcinols
      (AR), phenolic acids, phytosterols, and tocols in six whole wheat products and
      characterized their antioxidant capacity and ability to induce quinone reductase
      activity (QR). Total AR content ranged from 136.8 to 233.9 ug/g and was
      correlated with whole wheat content (r = 0.9248; p = 0.0083). Ferulic acid (FerA)
      was the dominant phenolic at 99.9-316.0 ug/g and mostly bound tightly to the
      wheat matrix. AR-C21 and total FerA predicted the whole wheat content in each
      product (R(2 )= 0.9933). Total phytosterol content ranged from 562.6 to 1035.5
      ug/g. Total tocol content ranged from 19.3 to 292.7 ug/g. Phytosterol and tocol
      contents were independent of whole wheat content. Whole wheat biscuits and pasta
      were the most potent products to induce QR in Hepa1c1c7 cells. This study
      provides a platform to characterize the relationship between the phytochemical
      composition of whole wheat and products formulated with this whole grain.

PMID- 25578768
TI  - Detection of effects caused by very low levels of contaminants in riverine
      sediments through a combination of chemical analysis, in vitro bioassays, and
      farmed fish as sentinel.
AB  - Aquatic organisms are often exposed to mixtures of low levels of pollutants whose
      presence and effects can pass easily unnoticed if only traditional monitoring
      strategies are employed. The main aim of this work was to assess the presence and
      effects of trace levels of pollutants in a scarcely affected area through the
      combination of chemical and biological approaches. Sediments were collected along
      a river with little anthropogenic pressure and assayed for cytochrome P450
      (Cyp1a)-dependent ethoxyresorufin-O-deethylase (EROD) activity with the rainbow
      trout gonadal cell line RTG-2. Chemical analyses were performed in these
      sediments using two-dimensional gas chromatography-time-of-flight mass
      spectrometry. Sediment samples induced EROD activity, and chemical analyses
      evidenced the presence of a wide variety of contaminants in the range of
      nanograms per gram of dry weight. Correlation analysis between EROD induction and
      chemical analyses data showed an r value of 0.840 (p < 0.05). In addition, fish
      from a fish farm located downstream of the sampling points exhibited high hepatic
      EROD levels as well as an induced expression of cyp1a and cyp3a. In conclusion,
      only an appropriate combination of biological and chemical techniques allowed the
      detection of the presence of trace levels of contaminants in a theoretically
      nonaffected river.

PMID- 25578769
TI  - Assessing the risk of false negative point-of-care urinary human chorionic
      gonadotropin device results due to beta core fragment.

PMID- 25578770
TI  - Medical laboratory science registration and competence.

PMID- 25578771
TI  - HER2 assessment by silver in situ hybridization: where are we now?
AB  - HER2 testing in breast and gastric cancer is critical not only as a prognostic
      tool but also as a predictive marker for response to the humanized monoclonal
      antibody trastuzumab. Currently, HER2 status is assessed on histological and
      cytological specimens by conventional validated methods such as
      immunohistochemistry and FISH, while bright-field in situ hybridization
      techniques, such as silver in situ hybridization and chromogenic in situ
      hybridization, may offer performance benefits over FISH. The major points are
      first, technical issues, advantages and disadvantages relevant to each methods,
      and their clinical implications and second, the well-known genetic heterogeneity
      of HER2, and the occurrence of polysomy of chromosome 17. This review aims to
      summarize the growing body of literature on the accuracy of bright-field in situ
      techniques, notably silver in situ hybridization, in assessing HER2 status, and
      to discuss the role of such methods in pathology practice. 

PMID- 25578774
TI  - Core substituted naphthalene diimide - metallo bisterpyridine supramolecular
      polymers: synthesis, photophysics and morphology.
AB  - A series of metallo Ru(ii), Fe(ii), Co(ii) bisterpyridine polymers were prepared
      with naphthalene diimide (NDI) groups inserted between two 4'-phenyl-2,2:6',2''
      terpyridine (phtpy) groups. Core-substituted NDIs typically have long-lived
      excited states with relatively high quantum yields, yet the NDI emission in these
      metallopolymers was completely quenched, most likely because of efficient
      electron-transfer from the M(phtpy)2(2+) groups to the excited NDIs. AFM, TEM and
      SEM experiments indicate that the regiochemistry of the substitution on the core
      of the naphthalene diimide, together with coordination of the terpyridine ligand
      to different metals, strongly influences the morphologies of the resulting
      metallosupramolecular polymers. The morphologies of spin-coated samples of the
      para-substituted polymers revealed the formation of long, bundled nanorods.
      Lengths on the order of ~8 MUm were observed for the bundle of the longest
      polymers (-Ru) by both AFM and TEM microscopy. The morphologies of the meta
      substituted polymers, on the other hand, exhibited significantly shorter and less
      well-defined morphologies. 

PMID- 25578775
TI  - CNV Concordance in 1,097 MZ Twin Pairs.
AB  - Monozygotic (MZ) twins are genetically identical at conception, making them
      informative subjects for studies on somatic mutations. Copy number variants
      (CNVs) are responsible for a substantial part of genetic variation, have
      relatively high mutation rates, and are likely to be involved in phenotypic
      variation. We conducted a genome-wide survey for post-twinning de novo CNVs in
      1,097 MZ twin pairs. Comparisons between MZ twins were made by CNVs measured in
      DNA from blood or buccal epithelium with the Affymetrix 6.0 microarray and two
      calling algorithms. In addition, CNV concordance rates were compared between the
      different sources of DNA, and gene-enrichment association analyses were conducted
      for thought problems (TP) and attention problems (AP) using CNVs concordant
      within MZ pairs. We found a total of 153 putative post-twinning de novo CNVs >100
      kb, of which the majority resided in 15q11.2. Based on the discordance of raw
      intensity signals a selection was made of 20 de novo CNVs for a qPCR validation
      experiments. Two out of 20 post-twinning de novo CNVs were validated with qPCR in
      the same twin pair. The 13-year-old MZ twin pair that showed two discordances in
      CN in 15q11.2 in their buccal DNA did not show large phenotypic differences. From
      the remaining 18 putative de novo CNVs, 17 were deletions or duplications that
      were concordant within MZ twin pairs. Concordance rates within twin pairs of CNV
      calls with CN ? 2 were ~80%. Buccal epithelium-derived DNA showed a slightly but
      significantly higher concordance rate, and blood-derived DNA showed significantly
      more concordant CNVs per twin pair. The gene-enrichment analyses on concordant
      CNVs showed no significant associations between CNVs overlapping with genes
      involved in neuronal processes and TP or AP after accounting for the source of
      DNA. 

PMID- 25578778
TI  - Suggestive evidence on the involvement of polypyrimidine-tract binding protein in
      regulating alternative splicing of MAP/microtubule affinity-regulating kinase 4
      in glioma.
AB  - MAP/microtubule affinity-regulating kinase 4 (MARK4) is a serine-threonine kinase
      that phosphorylates microtubule-associated proteins taking part in the regulation
      of microtubule dynamics. MARK4 is expressed in two spliced isoforms characterized
      by inclusion (MARK4S) or exclusion (MARK4L) of exon 16. The distinct expression
      profiles in the central nervous system and their imbalance in gliomas point to
      roles of MARK4L and MARK4S in cell proliferation and cell differentiation,
      respectively. Having ruled out mutations and transcription defects, we
      hypothesized that alterations in the expression of splicing factors may underlie
      deregulated MARK4 expression in gliomas. Bioinformatic analysis revealed four
      putative polypyrimidine-tract binding (PTB) protein binding sites in MARK4
      introns 15 and 16. Glioma tissues and glioblastoma-derived cancer stem cells
      showed, compared with normal brain, significant overexpression of PTB, correlated
      with high MARK4L mRNA expression. Splicing minigene assays revealed a functional
      intronic splicing silencer in MARK4 intron 15, but mutagenesis of the PTB binding
      site in this region did not affect minigene splicing, suggesting that PTB may
      bind to a splicing silencer other than the predicted one and synergistically
      acting with the other predicted PTB sites. Electrophoretic mobility shift assays
      coupled with mass spectrometry confirmed binding of PTB to the polypyrimidine
      tract of intron 15, and thus its involvement in MARK4 alternative splicing. This
      finding, along with evidence of PTB overexpression in gliomas and glioblastoma
      derived cancer stem cells and differentiated progeny, merged in pointing out the
      involvement of PTB in the switch to MARK4L, consistent with its established role
      in driving oncogenic splicing in brain tumors. 

PMID- 25578779
TI  - Heterogeneous expression and biological function of ubiquitin carboxy-terminal
      hydrolase-L1 in osteosarcoma.
AB  - Ubiquitin carboxyl terminal hydrolase 1 (UCHL1), a member of the UCH class of
      DUBs, has been reported as either an oncogene or a tumor suppressor. However, the
      molecular mechanism underlying the biological function of UCHL1 in osteosarcoma
      is still unclear. This study was aimed at elucidating the roles of UCHL1 in
      regulating the biological behavior of osteosarcoma cells. In this study, we found
      that UCHL1 was elevated in osteosarcoma compared with normal bone tissue.
      Moreover, UCHL1 expression level was correlated with tumor maximum diameter, high
      rate of lung metastases and short survival time. Then, we found that knockdown of
      UCHL1 in osteosarcoma cell MG63 inhibited cell proliferation and significantly
      increased cell population in the G1 phase. Several cyclins promoting G1/S phase
      transition were reduced after UCHL1 knockdown, including cell cycle regulator
      cyclin D1, cyclin E1 and CDK6. Moreover, inhibition of UCHL1 in MG63 cells
      dramatically induced cell apoptosis. We also found that down-regulation of UCHL1
      in MG63 significantly inhibited cell invasion. Then, we found that there was a
      positive correlation between UCHL1 expression level and the Akt and ERK
      phosphorylation status. Finally, in vivo data showed that knockdown of UCHL1
      inhibited osteosarcoma growth in nude mice. These results indicate that UCHL1
      could work as an oncogene and may serve as a promising therapeutic strategy for
      osteosarcoma. 

PMID- 25578780
TI  - Knockdown of long non-coding RNA XIST exerts tumor-suppressive functions in human
      glioblastoma stem cells by up-regulating miR-152.
AB  - Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Great
      interest persists in useful therapeutic targets in GBM. Aberrant expression of
      long non-coding RNAs (lncRNAs) has been functionally associated with many
      cancers. Here, we elucidated the function and the possible molecular mechanisms
      of lncRNA XIST in human glioblastoma stem cells (GSCs). Our results proved that
      XIST expression was up-regulated in glioma tissues and GSCs. Functionally,
      knockdown of XIST exerted tumor-suppressive functions by reducing cell
      proliferation, migration and invasion as well as inducing apoptosis. The in vivo
      studies also showed that knockdown of XIST suppressed tumor growth and produced
      high survival in nude mice. Further, there was reciprocal repression between XIST
      and miR-152. Mechanistic investigations defined the direct binding ability of the
      predicted miR-152 binding site on the XIST. In addition, XIST and miR-152 are
      probably in the same RNA induced silencing complex (RISC). Finally, miR-152
      mediated the tumor-suppressive effects that knockdown of XIST exerted. Taken
      together, these results provided a comprehensive analysis of XIST in GSCs and
      important clues for understanding the key roles of lncRNA-miRNA functional
      network in human glioma. 

PMID- 25578781
TI  - Advances in targeted therapy for unresectable melanoma: new drugs and
      combinations.
AB  - Melanoma is the most deadly cutaneous cancer primarily derived from melanocytes
      with a poor prognosis in advanced stage. The therapy regimen for early stage
      melanoma patients is surgical resection with adjuvant IFN-alpha-2b therapy. For
      metastatic lesions, standard chemotherapy such as dacarbazine (DTIC) has not
      achieved a satisfying response rate. Therefore, new approaches to manage this
      deadly disease are highly expected to enhance the cure rate and to extend
      clinical benefits to patients with unresectable melanoma. Fortunately, the
      targeted therapeutic drugs and immunotherapy such as vemurafenib, dabrafenib,
      ipilimumab, and trametinib have shown their special advantage in the treatment of
      advanced melanoma. This article is to overview the advances in targeted therapy
      for unresectable melanoma patients. 

PMID- 25578782
TI  - NFkappaB up-regulation of glucose transporter 3 is essential for hyperactive
      mammalian target of rapamycin-induced aerobic glycolysis and tumor growth.
AB  - Accumulating evidence indicates that mammalian target of rapamycin (mTOR) exerts
      a crucial role in aerobic glycolysis and tumorigenesis, but the underlying
      mechanisms remain largely obscure. Results from Tsc1- or Tsc2-null mouse
      embryonic fibroblasts (MEFs) and human cancer cell lines consistently indicate
      that the expression of glucose transporter 3 (Glut3) is dramatically up-regulated
      by mTOR. The rapamycin-sensitive mTOR complex 1 (mTORC1), but not the rapamycin
      insensitive mTOR complex 2 (mTORC2), was involved in the regulation of Glut3
      expression. Moreover, mTORC1 enhances Glut3 expression through the activation of
      the IKK/NFkappaB pathway. Depletion of Glut3 led to the suppression of aerobic
      glycolysis, the inhibition of cell proliferation and colony formation, and the
      attenuation of the tumorigenic potential of the cells with aberrantly hyper
      activated mTORC1 signaling in nude mice. We conclude that Glut3 is a downstream
      target of mTORC1, and it is critical for oncogenic mTORC1-mediated aerobic
      glycolysis and tumorigenesis. Hence Glut3 may be a potential target for therapy
      against cancers caused by the aberrantly activated mTORC1 signaling. 

PMID- 25578783
TI  - Diffusion-weighted magnetic resonance imaging for predicting and detecting the
      response of ocular melanoma to proton beam therapy: initial results.
AB  - PURPOSE: The aim of this study was to investigate the utility of diffusion
      weighted magnetic resonance (MR) imaging for prediction and early detection of
      response to proton beam therapy in ocular melanoma. MATERIALS AND METHODS: Ten
      ocular melanoma patients treated with proton beam therapy were enrolled in the
      study. All patients underwent conventional MR imaging and diffusion-weighted
      imaging (DWI) before the start of therapy, and after 1, 3 and 6 months of
      therapy. Tumour volumes and apparent diffusion coefficient (ADC) values of ocular
      lesions were measured at each examination. Tumour volumes and mean ADC
      measurements of the four examination series were compared; correlation of ADC
      values and tumour regression was investigated. RESULTS: Mean ADC value of ocular
      melanomas significantly increased as early as 3 months after therapy; tumour
      volume significantly decreased as early as 6 months after therapy. The ADC values
      of ocular melanomas before therapy significantly correlated with tumour
      regression. CONCLUSIONS: DWI may provide an early surrogate biomarker for
      prediction and early detection of tumour response to eye-preserving therapies in
      ocular melanoma.

PMID- 25578785
TI  - Enzyme-based logic systems interfaced with signal-responsive materials and
      electrodes.
AB  - Enzyme-based biocomputing systems were interfaced with signal-responsive
      membranes and electrodes resulting in bioelectronic devices switchable by
      logically processed biomolecular signals. "Smart" membranes, electrodes, biofuel
      cells, memristors and substance-releasing systems were activated by various
      combinations of biomolecular signals in the pre-programmed way implemented in
      biocatalytic cascades mimicking logic networks. 

PMID- 25578784
TI  - MR imaging-guided prostate biopsy: technical features and preliminary results.
AB  - PURPOSE: Repeatedly negative prostate biopsies in individuals with elevated
      prostate-specific antigen (PSA) levels can be frustrating for both the patient
      and the urologist. This study was performed to investigate if magnetic resonance
      imaging (MRI)-guided transrectal biopsy (MRGB) increases diagnostic performance
      in individuals with suspected prostate cancer (PCa). MATERIALS AND METHODS:
      Twenty-three consecutive men with a total PSA >4 ng/mL, PSA density >0.15, PSA
      velocity >0.75 ng/mL/year and suspicious MRI findings were included (average age
      64 years; age range 53-75 years; total PSA levels ranging from 4.7 to 54 ng/mL;
      median 9 ng/mL). MRGB was performed with a closed unit at 1.5 Tesla, an MRI
      compatible biopsy device, a needle guide, and a titanium double-shoot biopsy gun.
      RESULT: At prebiopsy MRI, in the 23 patients, a total of 26 suspicious areas to
      which the MRGB should be directed were found, 23 of them in the peripheral zone
      and three in the transitional zone. The needle guide was depicted and could be
      positioned with MRI guidance in all 23 patients. The duration of the procedure
      ranged from 35 to 55 min (mean 40 min). MRGB was well tolerated by all patients,
      and no major complications were observed. The detection rate for the diagnosis of
      PCa was 80, and 90 % of detected PCa were of intermediate aggressiveness.
      CONCLUSION: MRGB has the potential to improve cancer detection rates in men with
      suspected PCa to deliver the relevant treatment as soon as possible.

PMID- 25578786
TI  - Computed tomography angiography for prediction of atrial fibrillation after
      coronary artery bypass grafting: proof of concept.
AB  - BACKGROUND: Postoperative atrial fibrillation (AF) is a serious complication of
      coronary artery bypass grafting (CABG). There are scant data on the application
      of coronary computed tomography angiography (CCTA) for prediction of
      postoperative AF. METHODS: A total of 102 patients (77 male, mean age: 64+/-10
      years) with pre-procedural CCTA undergoing isolated CABG were enrolled. Clinical
      risk factors were collected. Qualitative and quantitative CCTA analysis of the
      atria, pulmonary veins (PV), and epicardial adipose tissue (EAT) along the left
      atrium (LA) was performed to determine the predictors for postoperative AF. The
      primary endpoint was defined as any in-hospital AF requiring treatment. RESULTS:
      Postoperative AF occurred in 24% of patients. Patients with AF had higher body
      mass index (29.7+/-4.8kg/m(2) vs 27.3+/-3.9kg/m(2), p=0.013), larger right atrial
      area (25.4+/-5.3cm(2) vs 22.3+/-6.4cm(2), p=0.035), LA systolic volume (114.7+/
      32.8ml vs 96.8+/-30.4ml, p=0.015), LA EAT volume (5.6+/-3ml vs 4+/-2.5ml,
      p=0.009), and right superior PV ostium area (3.8+/-1.3cm(2) vs 3+/-1cm(2),
      p=0.021) compared to non-AF patients. By multivariable analysis, only LA EAT
      volume [odds ratio (OR): 1.21, 95% confidence interval (CI): 1.01-1.44, p=0.036]
      and right superior PV ostium area (OR: 1.63, 95% CI: 1.06-2.50, p=0.026) were
      independent predictors of AF. The optimal cut-offs for LA EAT volume and right
      superior PV ostium were >3.4ml and >4.1cm(2), respectively (max. sensitivity:
      83%, max. specificity: 86%). CONCLUSIONS: Increased LA EAT and right superior PV
      ostial size are independently associated with AF after CABG. CCTA might be used
      as a noninvasive prediction tool for AF in patients undergoing CABG.

PMID- 25578787
TI  - The prognostic impact of worsening renal function in Japanese patients undergoing
      percutaneous coronary intervention with acute coronary syndrome.
AB  - BACKGROUND: The prognostic impact of worsening renal function (WRF) in acute
      coronary syndrome (ACS) patients is not fully understood in Japanese clinical
      practice, and clinical implication of persistent versus transient WRF in ACS
      patients is also unclear. METHODS: With a single hospital-based cohort in the
      Shinken database 2004-2012 (n=19,994), we followed 604 ACS patients who underwent
      percutaneous coronary intervention (PCI). WRF was defined as an increase in
      creatinine during hospitalization of >=0.3mg/dl above admission value. Persistent
      WRF was defined as an increase in creatinine during hospitalization of >=0.3mg/dl
      above admission value and maintained until discharge, whereas transient WRF was
      defined as that WRF resolved at hospital discharge. RESULTS: WRF occurred in 78
      patients (13%), persistent WRF 35 patients (6%) and transient WRF 43 patients
      (7%). WRF patients were older and had a higher prevalence of chronic kidney
      disease, history of myocardial infarction (MI), and ST elevation MI. WRF was
      associated with elevated inflammatory markers and reduced left ventricular (LV)
      ejection fraction in acute, chronic phase. Incidence of all-cause death and major
      adverse cardiac events (MACE: all-cause death, MI, and target lesion
      revascularization) was significantly higher in patients with WRF. Moreover, in
      the WRF group, incidences of all-cause death and MACE were higher in patients
      with persistent WRF than those with transient WRF. A multivariate analysis showed
      that as well as older age, female gender, and intubation, WRF was an independent
      determinant of the all-cause death in ACS patients who underwent PCI.
      CONCLUSIONS: In conclusion, WRF might have a prognostic impact among Japanese ACS
      patients who underwent PCI in association with enhanced inflammatory response and
      LV remodeling. Persistent WRF might portend increased events, while transient WRF
      might have association with favorable outcomes compared with persistent WRF.

PMID- 25578788
TI  - Hexagonal-like Nb2O5 nanoplates-based photodetectors and photocatalyst with high
      performances.
AB  - Ultraviolet (UV) photodetectors are important tools in the fields of optical
      imaging, environmental monitoring, and air and water sterilization, as well as
      flame sensing and early rocket plume detection. Herein, hexagonal-like Nb2O5
      nanoplates are synthesized using a facile solvothermal method. UV photodetectors
      based on single Nb2O5 nanoplates are constructed and the optoelectronic
      properties have been probed. The photodetectors show remarkable sensitivity with
      a high external quantum efficiency (EQE) of 9617%, and adequate wavelength
      selectivity with respect to UV-A light. In addition, the photodetectors exhibit
      robust stability and strong dependence of photocurrent on light intensity. Also,
      a low-cost drop-casting method is used to fabricate photodetectors based on Nb2O5
      nanoplate film, which exhibit singular thermal stability. Moreover, the hexagonal
      like Nb2O5 nanoplates show significantly better photocatalytic performances in
      decomposing Methylene-blue and Rhdamine B dyes than commercial Nb2O5.

PMID- 25578789
TI  - Prolapsing Gastric Polyp Causing Intermittent Gastric Outlet Obstruction.
AB  - Gastric polyps are often an incidental finding on upper gastrointestinal
      endoscopy, with an incidence up to 5%. The majority of gastric polyps are
      asymptomatic, occurring secondary to inflammation. Prior reviews discussed
      Helicobacter pylori (H pylori)-associated singular gastric polyposis; however, we
      present a rare and unusual case of recurrent multiple benign gastric polyposis
      post H pylori eradication resulting in intermittent gastric outlet obstruction. A
      70-year-old independent male, Chinese in ethnicity, with a background of diabetes
      mellitus, hypertension, and a simple renal cyst presented with a combination of
      melena, anemia, and intermittent vomiting of partially digested food after meals.
      Initial gastroscopy was positive for H pylori; thus he was treated with H pylori
      eradication and proton pump inhibitors. Serial gastroscopy demonstrated multiple
      sessile gastric antral polyps, the largest measuring 4 cm. Histopathologic
      examination confirmed a benign hyperplastic lesion. Computed tomography
      identified a pyloric mass with absent surrounding infiltration or metastasis. A
      distal gastrectomy was performed, whereby multiple small pyloric polyps were
      found, the largest prolapsing into the pyloric opening, thus explaining the
      intermittent nature of gastric outlet obstruction. Such polyps often develop from
      gastric ulcers and, if left untreated, may undergo neoplasia to form malignant
      cells. A distal gastrectomy was an effective choice of treatment, taking into
      account the polyp size, quantity, and potential for malignancy as opposed to an
      endoscopic approach, which may not guarantee a complete removal of safer margins
      and depth. Therefore, surgical excision is favorable for multiple large gastric
      polyps with risk of malignancy. 

PMID- 25578790
TI  - A case of posterior reversible encephalopathy syndrome associated with acute
      pancreatitis and chronic alcoholism.
AB  - Posterior reversible encephalopathy syndrome (PRES) is known to be caused by a
      variety of clinical disorders. The authors encountered a case of PRES associated
      with acute pancreatitis and chronic alcoholism. A 49-year-old man presented with
      altered mental status. Magnetic resonance imaging (MRI) displayed vasogenic edema
      at the bilateral posterior temporal and parieto-occipital lobes and cerebellum.
      Laboratory tests and abdominal computed tomography (CT) revealed acute
      pancreatitis. The patient recovered completely, and follow-up brain MRI and
      abdominal CT exhibited resolution of the previous lesions. We suggest that acute
      pancreatitis might be an etiology of PRES. 

PMID- 25578791
TI  - Prevalence of behavioral health disorders and associated chronic disease burden
      in a commercially insured health system: findings of a case-control study.
AB  - OBJECTIVE: The objective was to examine prevalence of behavioral health disorders
      (BHDs) and co-occurring chronic medical conditions in a 3.4 million-member
      integrated health system. METHOD: Clinical databases identified 255,993 patients
      diagnosed with the most prevalent BHDs (cases): depression, anxiety, substance
      use, bipolar spectrum and attention deficit and hyperactivity (ADHD); non-BHD
      matched controls were created for all unique cases. Cases and controls were
      compared for prevalence of general medical conditions and specific chronic
      diseases and the Charlson Comorbidity Index (CMI). RESULTS: The five most common
      BHDs were depression (58%), anxiety (42%), substance use (16%), bipolar spectrum
      (6%) and ADHD (4%). Compared to controls, patients with depression (80.1% vs.
      66.3%), anxiety (78.0% vs. 63.0%), substance use (74.0% vs. 59.9%), bipolar
      (75.3% vs. 60.7%) and ADHD (60.6% vs. 53.1%; all P<.001) had significantly higher
      prevalence of any medical comorbidities. Excluding ADHD, BHD cases had higher
      prevalence of selected chronic diseases and average CMI. CONCLUSIONS: BHDs in a
      largely commercially insured, employment-based health system are common and
      associated with a disproportionately higher burden of chronic medical disease and
      associated 10-year mortality risk rate. Given that co-occurrence of behavioral
      and medical conditions leads to elevated symptom burden, functional impairment,
      and healthcare costs, these findings highlight the importance of developing
      effective collaborative models of care in (nonpublic) employment-based health
      systems.

PMID- 25578794
TI  - Effect of parasympathetic stimulation on brain activity during appraisal of
      fearful expressions.
AB  - Autonomic nervous system activity is an important component of human emotion.
      Mental processes influence bodily physiology, which in turn feeds back to
      influence thoughts and feelings. Afferent cardiovascular signals from arterial
      baroreceptors in the carotid sinuses are processed within the brain and
      contribute to this two-way communication with the body. These carotid
      baroreceptors can be stimulated non-invasively by externally applying focal
      negative pressure bilaterally to the neck. In an experiment combining functional
      neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested
      the hypothesis that manipulating afferent cardiovascular signals alters the
      central processing of emotional information (fearful and neutral facial
      expressions). Carotid stimulation, compared with sham stimulation, broadly
      attenuated activity across cortical and brainstem regions. Modulation of
      emotional processing was apparent as a significant expression-by-stimulation
      interaction within left amygdala, where responses during appraisal of fearful
      faces were selectively reduced by carotid stimulation. Moreover, activity
      reductions within insula, amygdala, and hippocampus correlated with the degree of
      stimulation-evoked change in the explicit emotional ratings of fearful faces.
      Across participants, individual differences in autonomic state (heart rate
      variability, a proxy measure of autonomic balance toward parasympathetic
      activity) predicted the extent to which carotid stimulation influenced neural
      (amygdala) responses during appraisal and subjective rating of fearful faces.
      Together our results provide mechanistic insight into the visceral component of
      emotion by identifying the neural substrates mediating cardiovascular influences
      on the processing of fear signals, potentially implicating central baroreflex
      mechanisms for anxiolytic treatment targets. 

PMID- 25578795
TI  - Reduction in Ventral Midbrain NMDA Receptors Reveals Two Opposite Modulatory
      Roles for Glutamate on Reward.
AB  - Glutamate is a major component of the reward circuitry and recent clinical
      studies suggest that new molecules that would target glutamate neurotransmission
      are most likely to constitute more effective medications for mood disorders. It
      is well known that activation of N-methyl-D-aspartate glutamate receptors
      (NMDARs) initiates dopamine burst firing, a mode associated with reward
      signaling; but NMDARs also contribute to the maintenance of an inhibitory drive
      to dopamine neurons. Such opposite modulatory functions imply that different
      subtypes of NMDARs are expressed on different ventral midbrain (VM) neurons
      and/or afferent inputs to dopamine neurons. By using the small interfering RNA
      (siRNA) technique, we studied the effects of VM downregulation of NMDAR subunits
      GluN1, GluN2A, and GluN2D on reward induced by dorsal raphe electrical
      stimulation. Reward thresholds were measured before and 24 h after each of three
      consecutive daily bilateral microinjections of siRNA for the targeted receptor
      subunit(s) or non-active RNA sequence. After the last measurement, reward
      thresholds were reassessed following a bilateral microinjection of the preferred
      GluN2A-NMDA antagonist, (2R,4S)-4-(3-Phosphopropyl)-2-piperidinecarboxylic acid
      (PPPA). Western-blot analysis showed that siRNAs reduced GluN1- and GluN2A
      containing receptors whereas behavioral tests showed that only a reduction in
      GluN1 produced reward attenuation. Despite NMDAR reduction, reward-enhancing
      effect of PPPA remained unchanged. We conclude that VM glutamate relays the
      reward signal initiated by dorsal raphe electrical stimulation by acting on
      NMDARs devoid of GluN2A/2D subunits and exerts an inhibition on this reward
      signal by acting on GluN2A-containing NMDARs most likely located on afferent
      terminals. 

PMID- 25578797
TI  - Upregulation of dopamine D2 receptors in the nucleus accumbens indirect pathway
      increases locomotion but does not reduce alcohol consumption.
AB  - Brain imaging studies performed in humans have associated low striatal dopamine
      release and D2R binding with alcohol dependence. Conversely, high striatal D2R
      binding has been observed in unaffected members of alcoholic families suggesting
      that high D2R function may protect against alcohol dependence. A possible
      protective role of increased D2R levels in the striatum is further supported by
      preclinical studies in non-human primates and rodents. Here, we determined
      whether there is a causal relationship between D2R levels and alcohol intake. To
      this end, we upregulated D2R expression levels in the nucleus accumbens of the
      adult mouse, but selectively restricted the upregulation to the indirect striatal
      output pathway, which endogenously expresses D2Rs. After overexpression was
      established, mice were tested in two models of free-choice alcohol drinking: the
      continuous and intermittent access two-bottle choice models. As anticipated, we
      found that D2R upregulation leads to hyperactivity in the open field. Contrary to
      our expectation, D2R upregulation did not reduce alcohol intake during continuous
      or intermittent access or when alcohol drinking was tested in the context of
      aversive outcomes. These data argue against a protective role of accumbal
      indirect pathway D2Rs in alcohol consumption but emphasize their importance in
      promoting locomotor activity. 

PMID- 25578796
TI  - Resting-state connectivity predictors of response to psychotherapy in major
      depressive disorder.
AB  - Despite the heterogeneous symptom presentation and complex etiology of major
      depressive disorder (MDD), functional neuroimaging studies have shown with
      remarkable consistency that dysfunction in mesocorticolimbic brain systems are
      central to the disorder. Relatively less research has focused on the
      identification of biological markers of response to antidepressant treatment that
      would serve to improve the personalized delivery of empirically supported
      antidepressant interventions. In the present study, we investigated whether
      resting-state functional brain connectivity (rs-fcMRI) predicted response to
      Behavioral Activation Treatment for Depression, an empirically validated
      psychotherapy modality designed to increase engagement with rewarding stimuli and
      reduce avoidance behaviors. Twenty-three unmedicated outpatients with MDD and 20
      matched nondepressed controls completed rs-fcMRI scans after which the MDD group
      received an average of 12 sessions of psychotherapy. The mean change in Beck
      Depression Inventory-II scores after psychotherapy was 12.04 points, a clinically
      meaningful response. Resting-state neuroimaging data were analyzed with a seed
      based approach to investigate functional connectivity with four canonical resting
      state networks: the default mode network, the dorsal attention network, the
      executive control network, and the salience network. At baseline, the MDD group
      was characterized by relative hyperconnectivity of multiple regions with
      precuneus, anterior insula, dorsal anterior cingulate cortex (dACC), and left
      dorsolateral prefrontal cortex seeds and by relative hypoconnectivity with
      intraparietal sulcus, anterior insula, and dACC seeds. Additionally, connectivity
      of the precuneus with the left middle temporal gyrus and connectivity of the dACC
      with the parahippocampal gyrus predicted the magnitude of pretreatment MDD
      symptoms. Hierarchical linear modeling revealed that response to psychotherapy in
      the MDD group was predicted by pretreatment connectivity of the right insula with
      the right middle temporal gyrus and the left intraparietal sulcus with the
      orbital frontal cortex. These results add to the nascent body of literature
      investigating pretreatment rs-fcMRI predictors of antidepressant treatment
      response and is the first study to examine rs-fcMRI predictors of response to
      psychotherapy. 

PMID- 25578800
TI  - Repeated Dose 90-Day Feeding Study of Whole Fruits of Genetically Modified Papaya
      Resistant to Papaya Ringspot Virus in Rats.
AB  - Genetically modified (GM) papaya plants resistant to infection by Papaya ringspot
      virus (PRSV) have been successfully generated by cloning the coat protein (CP)
      gene of PRSV to increase fruit production. In this study, the GM papaya line 823
      2210 was used to conduct a 90-day feeding toxicity study and compared to its
      parent plant of non-GM papaya, Tainung-2 (TN-2) based on the experimental
      guidance reported by the European Food Safety Authority.1 Ten male and 10 female
      Sprague-Dawley albino rats were gavaged at low (1 g/kg bw) and high (2 g/kg bw)
      doses of non-GM and GM lyophilized papaya fruits for 90 days. Hematology,
      coagulation, biochemistry, urinalysis, and pathology were examined in all
      animals. Although some differences were found in feed consumption, hematology,
      and serum chemistry examinations between non-GM and GM papaya, the results were
      within historical control values and not considered biologically significant in
      rats. In addition, there were no treatment-related gross or microscopic lesions
      in male or female rats attributable to the non-GM or GM papaya fruit. This 90-day
      feeding study of GM papaya fruit did not reveal adverse effects in rats and
      indicates that GM papaya fruits may be substantially equivalent to their non-GM
      parent plants.

PMID- 25578798
TI  - Quantification of the Serotonin 1A Receptor Using PET: Identification of a
      Potential Biomarker of Major Depression in Males.
AB  - Multiple lines of research have implicated the serotonin 1A (5-HT1A) receptor in
      major depressive disorder (MDD). Despite this, quantification of 5-HT1A is yet to
      yield a clinically relevant MDD biomarker. One reason may be that reported sex
      differences in the serotonergic system confound the comparison between diagnostic
      groups. Therefore, this study sought to determine whether differences in 5-HT1A
      binding between depressed and control subjects are affected by sex. Using
      positron emission tomography (PET), serotonin 1A binding was quantified in 50
      patients with MDD (34 female, 16 male) and 57 healthy controls (32 female, 25
      male). The subjects' 5-HT1A density (BPF, equal to the product of the density of
      available receptors and tracer affinity), was determined by using the PET tracer
      [carbonyl-C-11]-WAY-100635, a selective 5-HT1A antagonist. Results indicated that
      male MDD subjects had a 67.0% higher BPF across 13 brain regions compared with
      male controls (df=103, p<0.0001). The greatest difference between MDD subjects
      and controls was in the raphe (132%, p=0.000). Furthermore, by using a threshold,
      male controls can be distinguished from depressed males with high sensitivity and
      specificity (both >80%). In females, the separation between diagnostic groups
      yields much lower sensitivity and specificity. This data therefore suggests a
      specific biosignature for MDD in males. Identification of such a biosignature
      could provide a deeper understanding of depression pathology, help identify those
      at highest risk, and aid in the development of new therapies. Further, these
      findings suggest that combining male and female cohorts may not be optimal for
      some MDD studies. 

PMID- 25578803
TI  - Templated self-assembly of block copolymers and morphology transformation driven
      by the Rayleigh instability.
AB  - In the current study, we investigate the self-assembly of polystyrene-block
      poly(4-vinylpyridine) (PS-b-P4VP) confined in the nanopores of the anodic
      aluminum oxide (AAO) template and the subsequent morphology transformation
      induced by the Rayleigh instability. PS-b-P4VP nanotubes and nanorods with
      various internal nanostructures are fabricated by wetting the AAO template with
      PS-b-P4VP/chloroform solution, and then followed by solvent evaporation. After
      the removal of AAO template by potassium hydroxide solution, several different
      solvents (chloroform, toluene, and N,N-dimethylformamide) with different
      qualities are used to swell and anneal those nanotubes and nanorods suspended in
      aqueous media. Morphology transformation from nanostructured PS-b-P4VP nanotubes
      or nanorods to ordered nanospheres is observed by annealing upon chloroform and
      toluene while the morphology remains unchanged upon N,N-dimethylformamide
      annealing, indicating that solvent quality is a key factor in tuning the
      morphology and internal structures. Kinetics study and theoretical analysis for
      the morphology transition from two-dimensional (2D) block copolymer (BCP)
      nanotubes and nanorods to three-dimensional (3D) BCP nanospheres are further
      performed. From the morphological evolution and the quantitative calculation, it
      is confirmed that this transition is induced by the Rayleigh instability. This
      study provides a simple but promising method, that is, solvent annealing method,
      for the fabrication of BCP nanospheres with ordered internal nanostructures,
      which may have great application in drug delivery and other nanotechnology. 

PMID- 25578802
TI  - Functional outcome and complications following reconstruction for Harrington
      class II and III periacetabular metastasis.
AB  - BACKGROUND: Metastatic bone disease involving the acetabulum is a debilitating
      condition causing significant pain and disability for patients. Many methods of
      reconstruction have been described for treating Harrington class II and III
      lesions with different results and complications. Our objectives were to report
      functional results, implant survival and complications following reconstruction
      for Harrington class II and III periacetabular metastases by using anti-protusio
      cages, screws and joint replacement. METHODS: We reviewed 22 patients undergoing
      acetabular reconstruction for metastatic disease. There were 5 Harrington class
      II and 17 class III lesions. Intralesional curettage, multiple screws and
      cemented total hip replacement were performed in all patients. Anti-protusio
      cages were used in 19 hips. No Steinmann pins were used. Sixteen patients died at
      a median survival time of 12 months (range, 4 to 28 months) after surgery. Six
      patients were alive at last follow-up at a median of 8 months (range, 3 to 15
      months). RESULTS: Postoperatively, the average ECOG score was improved from 3.1
      to 1.7 and Visual Analog Scale was improved from 8.4 to 2.2. One patient
      developed hip dislocation and one patient developed superficial infection. The
      mean Musculoskeletal Tumor Society (MSTS) functional score was 70 (range, 27 to
      87). There was no prosthetic loosening or revision. Twenty patients were able to
      walk. Eight patients became community ambulators, twelve became household
      ambulators and two were bed-bound. CONCLUSIONS: Good functional outcome and
      better ambulation could be expected following class II and III periacetabular
      reconstruction using anti-protusio cages, screws and cemented hip replacement.
      Few complications were noted and manageable. Although most of these patients with
      metastatic disease had limited life expectancies, their quality of life would be
      improved with appropriate patient selection and surgical reconstruction.

PMID- 25578804
TI  - PFAPA syndrome: Diagnosis in adulthood.

PMID- 25578805
TI  - Characterizing the metal-SAM interface in tunneling junctions.
AB  - This paper investigates the influence of the interface between a gold or silver
      metal electrode and an n-alkyl SAM (supported on that electrode) on the rate of
      charge transport across junctions with structure Met(Au or
      Ag)(TS)/A(CH2)nH//Ga2O3/EGaIn by comparing measurements of current density, J(V),
      for Met/AR = Au/thiolate (Au/SR), Ag/thiolate (Ag/SR), Ag/carboxylate (Ag/O2CR),
      and Au/acetylene (Au/C=CR), where R is an n-alkyl group. Values of J0 and beta
      (from the Simmons equation) were indistinguishable for these four interfaces.
      Since the anchoring groups, A, have large differences in their physical and
      electronic properties, the observation that they are indistinguishable in their
      influence on the injection current, J0 (V = 0.5) indicates that these four Met/A
      interfaces do not contribute to the shape of the tunneling barrier in a way that
      influences J(V). 

PMID- 25578799
TI  - Hippocampal-dorsolateral prefrontal coupling as a species-conserved cognitive
      mechanism: a human translational imaging study.
AB  - Hippocampal-prefrontal cortex (HC-PFC) interactions are implicated in working
      memory (WM) and altered in psychiatric conditions with cognitive impairment such
      as schizophrenia. While coupling between both structures is crucial for WM
      performance in rodents, evidence from human studies is conflicting and
      translation of findings is complicated by the use of differing paradigms across
      species. We therefore used functional magnetic resonance imaging together with a
      spatial WM paradigm adapted from rodent research to examine HC-PFC coupling in
      humans. A PFC-parietal network was functionally connected to hippocampus (HC)
      during task stages requiring high levels of executive control but not during a
      matched control condition. The magnitude of coupling in a network comprising HC,
      bilateral dorsolateral PFC (DLPFC), and right supramarginal gyrus explained one
      fourth of the variability in an independent spatial WM task but was unrelated to
      visual WM performance. HC-DLPFC coupling may thus represent a systems-level
      mechanism specific to spatial WM that is conserved across species, suggesting its
      utility for modeling cognitive dysfunction in translational neuroscience. 

PMID- 25578806
TI  - Resolution of sub-nanosecond motions in botulinum neurotoxin endopeptidase: An
      evidence of internal flexibility.
AB  - Botulinum neurotoxins (BoNTs) are the most poisonous substances known to mankind,
      which act on the peripheral nervous system leading to flaccid paralysis. Although
      co-crystal structure of BoNT/A light chain (LC) reveals some unique features of
      the biological function of this molecule, structural characteristics in solution
      reveal its dynamic features, not available through the published crystal
      structures. In this study, we have examined internal flexibility of this molecule
      by measuring rotational correlation time as a function of viscosity, using
      frequency domain fluorescence anisotropy decay technique. Fluorescence anisotropy
      decay of BoNT/A LC resolved sub-nanosecond local motion (faster component),
      interpreted as internal flexibility of the molecule was affected significantly
      with viscosity. Both local and global movements were affected by viscosity, which
      indicates the accessibility of protein core and flexibility of overall structure.
      In conclusion, this work demonstrates the presence of flexibility in the internal
      peptide segments, which appears to play a significant role in BoNT/A LC
      biological function. 

PMID- 25578807
TI  - Modulating protein-protein interactions: the potential of peptides.
AB  - Protein-protein interactions (PPIs) have emerged as important and challenging
      targets in chemical biology and medicinal chemistry. The main difficulty
      encountered in the discovery of small molecule modulators derives from the large
      contact surfaces involved in PPIs when compared with those that participate in
      protein-small molecule interactions. Because of their intrinsic features,
      peptides can explore larger surfaces and therefore represent a useful alternative
      to modulate PPIs. The use of peptides as therapeutics has been held back by their
      instability in vivo and poor cell internalization. However, more than 200 peptide
      drugs and homologous compounds (proteins or antibodies) containing peptide bonds
      are (or have been) on the market, and many alternatives are now available to
      tackle these limitations. This review will focus on the latest progress in the
      field, spanning from "lead" identification methods to binding evaluation
      techniques, through an update of the most successful examples described in the
      literature. 

PMID- 25578808
TI  - Recent developments in the study of molybdoenzyme models.
AB  - Over the past two decades, a plethora of crystal structures of molybdenum enzymes
      has appeared in the literature providing a clearer picture of the enzymatic
      active sites and increasing the challenge to chemists to develop accurate models
      for those sites. In this minireview we discuss the most recent model studies
      aimed to reproduce detailed features of the pterin-dithiolene ligand, both as the
      uncoordinated form and as a chelate coordinated to molybdenum. 

PMID- 25578809
TI  - Dual binding of 14-3-3 protein regulates Arabidopsis nitrate reductase activity.
AB  - 14-3-3 proteins represent a family of ubiquitous eukaryotic proteins involved in
      numerous signal transduction processes and metabolic pathways. One important 14-3
      3 target in higher plants is nitrate reductase (NR), whose activity is regulated
      by different physiological conditions. Intra-molecular electron transfer in NR is
      inhibited following 14-3-3 binding to a conserved phospho-serine motif located in
      hinge 1, a surface exposed loop between the catalytic molybdenum and central heme
      domain. Here we describe a novel 14-3-3 binding site within the NR N-terminus, an
      acidic motif conserved in NRs of higher plants, which significantly contributes
      to 14-3-3-mediated inhibition of NR. Deletion or mutation of the N-terminal
      acidic motif resulted in a significant loss of 14-3-3 mediated inhibition of
      Ser534 phosphorylated NR-Mo-heme (residues 1-625), a previously established model
      of NR regulation. Co-sedimentation and crosslinking studies with NR peptides
      comprising each of the two binding motifs demonstrated direct binding of either
      peptide to 14-3-3. Surface plasmon resonance spectroscopy disclosed high-affinity
      binding of 14-3-3omega to the well-known phospho-hinge site and low-affinity
      binding to the N-terminal acidic motif. A binding groove-deficient 14-3-3omega
      variant retained interaction to the acidic motif, but lost binding to the phospho
      hinge motif. To our knowledge, NR is the first enzyme that harbors two
      independent 14-3-3 binding sites with different affinities, which both need to be
      occupied by 14-3-3omega to confer full inhibition of NR activity under
      physiological conditions. 

PMID- 25578810
TI  - Interaction between dimer interface residues of native and mutated SOD1 protein:
      a theoretical study.
AB  - Cu-Zn superoxide dismutase 1 (SOD1) is a highly conserved bimetallic protein
      enzyme, used for the scavenging the superoxide radicals (O2 (-)) produced due to
      aerobic metabolism in the mitochondrial respiratory chain. Over 100 mutations
      have been identified and found to be in the homodimeric structure of SOD1. The
      enzyme has to be maintained in its dimeric state for the structural stability and
      enzymatic activity. From our investigation, we found that the mutations apart
      from the dimer interface residues are found to affect the dimer stability of
      protein and hence enhancing the aggregation and misfolding tendency of mutated
      protein. The homodimeric state of SOD1 is found to be held together by the non
      covalent interactions. The molecular dynamics simulation has been used to study
      the hydrogen bond interactions between the dimer interface residues of the
      monomers in native and mutated forms of SOD1 in apo- and holo-states. The results
      obtained by this analysis reveal the fact that the loss of hydrogen bond
      interactions between the monomers of the dimer is responsible for the reduced
      stability of the apo- and holo-mutant forms of SOD1. The conformers with dimer
      interface residues in native and mutated protein obtained by the molecular
      dynamics simulation is subjected to quantum mechanical study using M052X/6-31G(d)
      level of theory. The charge transfer between N-H...O interactions in the dimer
      interface residues were studied. The weak interaction between the monomers of the
      dimer accounts for the reduced dimerization and enhanced deformation energy in
      the mutated SOD1 protein. 

PMID- 25578812
TI  - An aerosol-based soft lithography to fabricate nanoscale silver dots and rings
      for spectroscopic applications.
AB  - Site-selective deposition of aerosol Pd nanoparticles on a substrate was employed
      to fabricate nanoscale Ag dots and rings through a subsequent electroless
      deposition. The fabricated nanoscale dot and ring arrays respectively showed
      properties in surface-enhanced Raman (SER, with a 1.8 * 10(5) enhancement factor)
      and Fourier transform near infrared (FT-NIR, at 6153 cm(-1) absorption band)
      spectra. 

PMID- 25578813
TI  - An uncommon presentation of a metachronous primary gastric tumor in a patient
      with a resected colorectal carcinoma: case report and review of the literature.

PMID- 25578814
TI  - Stroke-free status and depression scores among Saudi dialysis patients.
AB  - BACKGROUND: To assess the prevalence of stroke symptoms and depression among
      Saudi dialysis patients and related factors. METHODS: This is a cross-sectional
      multicentre study of Saudi dialysis patients. Demographics, clinical and
      laboratory's data were collected. Freedom from stroke symptoms was assessed using
      the Questionnaire for Verifying Stroke-Free Status and depression using the
      Geriatric Depression Scale. RESULTS: Five-hundred and forty-nine patients (77.3%
      response rate); 94.6% were receiving hemodialysis and 5.4% peritoneal dialysis
      were included in the study. Freedom from stroke was reported in 76.6% of
      patients, was higher in females (p = 0.07), and was not affected by the presence
      of diabetes mellitus coronary artery disease or peripheral vascular disease.
      However, it was significantly lower in hypertensive patients (p = 0.035) and was
      not affected by age, dialysis duration, Kt/V, albumin or hemoglobin levels. It
      was, however, more prevalent in the non-depressed patients compared to depressed
      patients (p = 0.036). Mild and major depression scores were noted in 45.2% and
      6.1%, respectively; the depression score being significantly higher in HD than in
      PD patients (6.3 +/- 3.4 vs. 5.0 +/- 3.2 p = 0.049) but was not related to sex,
      employment, vascular access type, age, dialysis duration, Kt/V or serum albumin
      or hemoglobin levels. CONCLUSION: A quarter of the patients were not stroke
      symptom-free and these were more likely the depressed patients, in females, but
      significantly less in hypertensive patients. Almost half of the patients were
      depressed with 6.1% having major depression. The depression score was
      significantly higher in HD than in PD patients.

PMID- 25578811
TI  - Carbon monoxide binding properties of domain-swapped dimeric myoglobin.
AB  - Myoglobin (Mb) is a monomeric oxygen storage hemoprotein, and has been shown to
      form a domain-swapped dimer. In this study, monomeric and dimeric carbon monoxide
      (CO)-bound Mb (MbCO) exhibited similar absorption spectra. The CO stretching
      frequencies of MbCO were observed at 1,932 and 1,944 cm(-1) for both monomeric
      and dimeric MbCO. The resonance Raman (RR) bands for the stretching between the
      heme iron and axial ligands were observed at the same frequencies for the monomer
      and dimer of deoxygenated Mb (deoxyMb) and MbCO, respectively (nu Fe-His, 220 cm(
      1); nu Fe-C, 507 cm(-1)), showing that the Fe-His bond strength of deoxyMb and
      the Fe-CO bond strength of MbCO did not change by the dimerization. Time-resolved
      RR measurements showed that the dynamics of the structural changes at the heme
      active site after CO photo-dissociation of MbCO was similar between monomeric and
      dimeric Mb [monomer, (5.2 +/- 1.8) * 10(6) s(-1); dimer, (6.2 +/- 1.1) * 10(6) s(
      1) at room temperature]. These results show that the heme coordination structure,
      the protein environment around the bound CO, and the protein relaxation character
      are similar between monomeric and dimeric MbCO. Although the active site
      structure was similar between the monomer and dimer, the CO binding rate constant
      of dimeric Mb [(1.01 +/- 0.03) * 10(6) M(-1) s(-1) at 20  degrees C] was about
      twice larger than that of the monomer [(0.52 +/- 0.02) * 10(6) M(-1) s(-1) at 20 
      degrees C], presumably due to the expansion of the channel between the Xe3 cavity
      and the solvent by the dimerization.

PMID- 25578815
TI  - Loss of matrix metalloproteinase-8 is associated with worsened recovery after
      ischemic kidney injury.
AB  - Acute kidney injury (AKI) leads to chronic kidney disease. The mechanisms
      involved with recovery from AKI are poorly understood and molecular mediators
      responsible for healing and restoration of kidney function are understudied. We
      previously discovered differential expression of matrix metalloproteinase-8 (MMP
      8) mRNA and protein in patients with severe sepsis associated AKI versus sepsis
      without AKI. Here, we demonstrate the involvement of MMP-8 in purely ischemic
      AKI. Mice subjected to 30 min of bilateral renal ischemia developed increased
      plasma creatinine and MMP-8 expression within 24 h versus sham controls. After an
      initial surge and subsequent return toward baseline, both kidney MMP-8 expression
      and activity exhibited a late increase (Days 5-7 post-ischemia reperfusion) in
      mice subjected to AKI. Neutrophil infiltration of the kidney was significantly
      higher after AKI in wild-type mice than in MMP-8 null mice, starting at 4 days.
      Additionally, MMP-8 null mice subjected to AKI demonstrated a persistent
      histopathologic and functional injury and worsened health (greater overall weight
      loss) versus wild-type cohorts after seven days. Taken together, our findings
      suggest that MMP-8 is involved with restoration of baseline kidney health after
      ischemic kidney injury and that a potential mechanism involves the interaction of
      MMP-8 and neutrophil recruitment to the site of injury.

PMID- 25578816
TI  - The relation between apelin levels, echocardiographic findings and carotid intima
      media thickness in peritoneal dialysis patients.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the most important cause of morbidity
      and mortality in patients with end stage renal disease (ESRD). Apelin expressed
      in endothelial and other tissues including brain and kidney is an adipocytokine
      defined recently and is emerging an important mediator of cardiovascular
      homeostasis. The aim of this study was to test whether apelin levels might be
      associated with carotid artery atherosclerosis and left ventricular mass index
      (LVMI) in peritoneal dialysis patients. PATIENTS AND METHODS: Fifty peritoneal
      dialysis patients (25 female, mean age 41.4 +/- 11.9 years, mean dialysis vintage
      65.0 +/- 35.4 months) and 18 healthy individuals (9 female, mean age 41.7 +/- 6.8
      years) were included in this cross-sectional study. Serum apelin 12 levels,
      echocardiographic findings and carotid intima media thickness (CIMT) were
      recorded as well as clinical and laboratory data. RESULTS: There were no
      differences between the patient and the control groups with regard to demographic
      characteristics. In patient group, LVMI, CIMT, CRP and apelin levels were
      elevated compared to control group. However there was no association between
      apelin, LVMI and CIMT. There was a positive correlation between apelin and CRP,
      which was not statistically significant. When patients were divided into two
      groups according to the mean serum apelin levels, LVMI, CIMT and CRP were higher
      in the high apelin group but this difference did not reach statistical
      significance. CONCLUSION: We observed an increased inflammation and CVD risk in
      peritoneal dialysis patients. However, serum apelin levels seem not to be
      associated with cardiovascular risk in this group of patients.

PMID- 25578817
TI  - Association between visit-to-visit clinic blood pressure variability and home
      blood pressure variability in patients with chronic kidney disease.
AB  - Although both clinic blood pressure (BP) variability and home BP variability are
      associated with the risk of cardiovascular disease, the relationship between both
      BP variabilities remain unclear. We evaluated the association between visit-to
      visit variability of clinic BP (VVV) and day-by-day home BP variability (HBPV) in
      patients with chronic kidney disease (CKD). We recruited 143 CKD patients in whom
      we performed HBP measurements every morning and evening over seven consecutive
      days. We obtained clinic BP data during 9.6 +/- 1.0 consecutive visits within 24
      months. The associations between the variables of VVV and HPBV were examined. The
      CV values of clinic systolic BP (CSBP) was significantly correlated with the mean
      values of morning systolic BP (MSBP) and those of evening systolic BP (ESBP) (r =
      0.23, 0.20; p = 0.007, 0.02, respectively). The CV values of CSBP was
      significantly correlated with the CV values of MSBP and those of ESBP (r = 0.19,
      0.31; p = 0.02, <0.001, respectively). On the multivariate regression analysis,
      the CV values of CSBP was significantly correlated with the CV values of MSBP and
      those of ESBP [standardized regression coefficient (beta) = 0.19, 0.34; p = 0.03,
      <0.001, respectively]. In conclusion, VVV showed a weak but significant
      association with HBPV, especially the CV values of ESBP in CKD patients. Further
      studies are necessary to clarify whether these different BPV elements will be
      alternative marker of BPV.

PMID- 25578819
TI  - [Small eye--very important].

PMID- 25578818
TI  - Omalizumab for difficult-to-treat dermatological conditions: clinical and
      immunological features from a retrospective real-life experience.
AB  - BACKGROUND: Omalizumab, a therapeutic monoclonal antibody specific for human IgE,
      has thus far been used as add-on therapy for moderate-to-severe allergic asthma
      in adults and children. OBJECTIVE: The objective of this study was to test
      omalizumab efficacy in other conditions in which the IgE-mast cell axis is
      supposed to play a role. METHODS: Nine patients with dermatological
      manifestations possibly related to activation of the IgE-mast cell axis (six
      chronic spontaneous urticaria and three atopic dermatitis patients) were
      administered off-label omalizumab because of refractoriness to standard therapy.
      All patients were subjected to strict clinical, laboratoristic, and imaging
      follow-up to monitor for possible adverse effects. In addition, to further assess
      the role of omalizumab on T cells, mast cells, and eosinophils, T-cell immune
      polarisation as well as eosinophil cationic protein and tryptase serum levels
      were determined before and during omalizumab administration. RESULTS: Therapy was
      effective in seven out of nine patients (six complete responses, one partial
      response, and two no responses). Interestingly, omalizumab appeared to induce
      lymphocyte polarisation toward a type 2 immune response and to be able to quench
      eosinophil-mediated inflammation, particularly in atopic dermatitis patients.
      Tryptase serum levels were generally low and remained unchanged during omalizumab
      treatment. Despite treatment spanning over several years in most of the patients,
      no adverse effects nor new ensuing medical conditions have thus far been observed
      (median follow-up: 42 months). CONCLUSIONS: Off-label omalizumab was safe and
      effective in our patients. The novel immunologic features recorded in our
      patients add further complexity to the mechanism of action of omalizumab.

PMID- 25578821
TI  - [Activities of the tissue transplantation and biotechnology section of the German
      Ophthalmological Society: 4. Performance report 2013].

PMID- 25578820
TI  - [Interobserver and intraobserver reliability of corneal surface temperature
      measurements with the TG-1000 thermograph in normal eyes].
AB  - PURPOSE: The aim of this study was to analyze the reliability of temperature
      measurements with the ocular TG-1000 thermograph in a setup of sequential
      measurements performed by one observer (intraobserver) and a sequence of
      measurements performed by different observers (interobserver) in normal subjects
      without pathologies of the anterior segment of the eye. PATIENTS AND METHODS: A
      total of 50 right eyes from 50 individuals (mean age 29.1 +/- 7.9 years) without
      ocular pathologies or history of ocular surgery were enrolled in this prospective
      monocentric clinical case series. Eyes with signs of dry eye syndrome (based on a
      positive McMonnies questionnaire) were excluded from the study. Corneal surface
      temperature measurements were performed by three examiners to assess
      interobserver reliability. In addition, in a subgroup of 22 individuals, a
      sequence of 3 measurements were performed by 1 of the examiners to examine
      intraobserver reliability. Corneal surface temperature was measured within an
      interval of 10 s (11 frames) on a region of interest of 16 +/- 12 mm (320 +/- 240
      pixels). Central and mid-peripheral local temperatures at 3 mm (3, 6, 9 and 12
      o'clock) were extracted and analyzed from the raw data. RESULTS: The ocular TG
      1000 thermograph yielded consistent results for the interobserver as well as
      intraobserver conditions in measuring corneal surface temperature in the center
      as well as mid-periphery of the cornea. Cronbach's alpha was 0.9 or higher at all
      corneal locations, which proves a high consistency of results for the
      interobserver and intraobserver measurements. The average corneal surface
      temperature ranged between 34.0  degrees C and 34.7  degrees C with a slight
      decrease from the upper temporal (9 and 12 o'clock) to the lower nasal (3 and 6
      o'clock) quadrants. CONCLUSION: The TG-1000 thermograph yielded consistent
      results of corneal surface temperature in individuals without anterior segment
      pathologies or history of ocular surgery. With the option of raw data export (11
      frames within 10 s with a lateral resolution of 320 * 240 pixels) the thermograph
      offers a wide range of new diagnostic options for a spatiotemporal analysis of
      corneal surface temperature.

PMID- 25578822
TI  - [Immunological graft rejection with Khodadoust line after "Descemet stripping
      automated endothelial keratoplasty" (DSAEK)].
AB  - BACKGROUND: Over the past decade endothelial keratoplasty has become the
      treatment of choice for patients with corneal endothelial dysfunction. METHODS:
      "Descemet stripping automated endothelial keratoplasty" (DSAEK) is one of the
      most widespread forms of posterior endothelial keratoplasty. An improvement of
      visual acuity is achieved more quickly after DSAEK and the reduced amount of
      transplanted tissue in DSAEK seems to result in fewer instances of immunological
      graft rejection. PROBLEMS: The clinical signs of immunological graft rejection
      after DSAEK are not yet well known. Typically, an immunological rejection episode
      is combined with the presence of corneal edema, Descemet folds and retrocorneal
      precipitates restricted to the graft but a classical Khodadoust line seems to be
      rare. RESULTS: The quick response after the combination of high-dose topical and
      systemic steroid therapy with steroid injection (80 MUg fortecortin) in the
      anterior chamber in our patient confirms the necessity of a prompt and rapid
      immunosuppression. CONCLUSIONS: Although the risk of graft rejection after DSAEK
      is rare, the use of immunosuppressants is important in both acute and long-term
      postoperative care of endothelial corneal transplantation.

PMID- 25578823
TI  - Compressed images for affinity prediction-2 (CIFAP-2): an improved machine
      learning methodology on protein-ligand interactions based on a study on caspase 3
      inhibitors.
AB  - The aim of this study is to propose an improved computational methodology, which
      is called Compressed Images for Affinity Prediction-2 (CIFAP-2) to predict
      binding affinities of structurally related protein-ligand complexes. CIFAP-2
      method is established based on a protein-ligand model from which computational
      affinity information is obtained by utilizing 2D electrostatic potential images
      determined for the binding site of protein-ligand complexes. The quality of the
      prediction of the CIFAP-2 algorithm was tested using partial least squares
      regression (PLSR) as well as support vector regression (SVR) and adaptive neuro
      fuzzy inference system (ANFIS), which are highly promising prediction methods in
      drug design. CIFAP-2 was applied on a protein-ligand complex system involving
      Caspase 3 (CASP3) and its 35 inhibitors possessing a common isatin sulfonamide
      pharmacophore. As a result, PLSR affinity prediction for the CASP3-ligand
      complexes gave rise to the most consistent information with reported empirical
      binding affinities (pIC(50)) of the CASP3 inhibitors.

PMID- 25578824
TI  - Broadening the debate over HIV and hormonal contraception.

PMID- 25578828
TI  - Solid lipid nanoparticles as nucleic acid delivery system: properties and
      molecular mechanisms.
AB  - Solid lipid nanoparticles (SLNs) have been proposed in the 1990s as appropriate
      drug delivery systems, and ever since they have been applied in a wide variety of
      cosmetic and pharmaceutical applications. In addition, SLNs are considered
      suitable alternatives as carriers in gene delivery. Although important advances
      have been made in this particular field, fundamental knowledge of the underlying
      mechanisms of SLN-mediated gene delivery is conspicuously lacking, an imperative
      requirement in efforts aimed at further improving their efficiency. Here, we
      address recent advances in the use of SLNs as platform for delivery of nucleic
      acids as therapeutic agents. In addition, we will discuss available technology
      for conveniently producing SLNs. In particular, we will focus on underlying
      molecular mechanisms by which SLNs and nucleic acids assemble into complexes and
      how the nucleic acid cargo may be released intracellularly. In discussing
      underlying mechanisms, we will, when appropriate, refer to analogous studies
      carried out with systems based on cationic lipids and polymers, that have proven
      useful in the assessment of structure-function relationships. Finally, we will
      give suggestions for improving SLN-based gene delivery systems, by pointing to
      alternative methods for SLNplex assembly, focusing on the realization of a
      sustained nucleic acid release. 

PMID- 25578825
TI  - Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis
      of observational studies.
AB  - BACKGROUND: The evidence from epidemiological research into whether use of
      hormonal contraception increases women's risk of HIV acquisition is inconsistent.
      We did a robust meta-analysis of existing data to provide summary estimates by
      hormonal contraceptive method which can be used to inform contraceptive
      guidelines, models, and future studies. METHODS: We updated a recent systematic
      review to identify and describe studies that met inclusion criteria. To ensure
      inclusion of more recent research, we searched PubMed for articles published
      after December, 2011, using the terms "hormonal contraception",
      "HIV/acquisition", "injectables", "progestin", and "oral contraceptive pills". We
      assessed statistical heterogeneity for these studies, and, when appropriate,
      combined point estimates by hormonal contraception formulation using random
      effects models. We assessed publication bias and investigated heterogeneity
      through subgroup and stratified analyses according to study population and design
      features. FINDINGS: We identified 26 studies, 12 of which met inclusion criteria.
      There was evidence of an increase in HIV risk in the ten studies of depot
      medroxyprogesterone acetate (pooled hazard ratio [HR] 1.40, 95% CI 1.16-1.69).
      This risk was lower in the eight studies done in women in the general population
      (pooled HR 1.31, 95% CI 1.10-1.57). There was substantial between-study
      heterogeneity in secondary analyses of trials (n=7, I(2) 51.1%, 95% CI 0-79.3).
      Although individual study estimates suggested an increased risk, substantial
      heterogeneity between two studies done in women at high risk of HIV infection
      (I(2) 54%, 0-88.7) precluded pooling estimates. There was no evidence of an
      increased HIV risk in ten studies of oral contraceptive pills (pooled HR 1.00,
      0.86-1.16) or five studies of norethisterone enanthate (pooled HR 1.10, 0.88
      1.37). INTERPRETATION: Our findings show a moderate increased risk of HIV
      acquisition for all women using depot medroxyprogesterone acetate, with a smaller
      increase in risk for women in the general population. Whether the risks of HIV
      observed in our study would merit complete withdrawal of depot
      medroxyprogesterone acetate needs to be balanced against the known benefits of a
      highly effective contraceptive. FUNDING: None.

PMID- 25578857
TI  - Cardiac and oxidative stress biomarkers in Trypanosoma evansi infected camels:
      diagnostic and prognostic prominence.
AB  - This study was conducted to investigate the level of cardiac and oxidative stress
      markers in camels infected with Trypanosoma evansi and to explore the diagnostic
      and prognostic value of cardiac troponin I (cTnI) and creatine kinase-myocardial
      band (CK-MB) in response to infection. Seventy four dromedary camels with
      clinical and laboratory evidence of trypanosomosis and 20 healthy controls were
      included in this study. Serum cTnI, CK-MB, CK, malondialdehyde (MDA) and super
      oxide dismutase (SOD) were measured. The values of cTnI, CK-MB, CK and MDA were
      significantly higher, whereas SOD level was lower in T. evansi infected camel.
      Successfully treated camels (n = 43) had lower levels of cTnI, CK-MB, CK and MDA,
      but higher level of SOD compared to camels with treatment failure. Both cTnI and
      CK-MB showed high degree of accuracy in predicting treatment outcome (success vs
      failure). The area under the curve for cTnI and CK-MB was 0.98 and 0.93,
      respectively. However, cTnI showed better sensitivity and specificity than CK-MB
      (Se = 96.8% vs 83.9% and Sp = 100% vs 88.5%, respectively). These results suggest
      that cTnI and CK-MB could be used as diagnostic and prognostic biomarkers in
      camels infected with T. evansi.

PMID- 25578856
TI  - Alternative outcomes for the multiple breath washout in children with CF.
AB  - BACKGROUND: The lung clearance index (LCI) measured by multiple-breath washout
      (MBW) has been proposed as an outcome for clinical trials; however, MBW is time
      consuming and LCI can be affected by breathing pattern. We aimed to evaluate
      moment ratios and abbreviated LCI in school-aged children with mild-to-moderate
      CF lung disease. METHODS: Using existing data from three studies we assessed the
      sensitivity of moment ratios and abbreviated LCIs to (i) detect mild-to-moderate
      CF lung disease and (ii) detect treatment effects after 4 weeks of hypertonic
      saline or dornase alfa inhalation. MBW was measured by respiratory mass
      spectrometry using 4% ""sulphur hexafluoride as a tracer gas. RESULTS: Compared
      to the traditional LCI, moment ratios and abbreviated LCIs were similarly
      sensitive to detect CF lung disease. Moment ratios consistently demonstrated
      treatment effects, whereas abbreviated LCIs were less sensitive. CONCLUSIONS:
      Both moment ratios and abbreviated LCI are suitable to differentiate health from
      disease. Sensitivity is decreased for abbreviated LCIs in interventional studies
      in mild CF lung disease.

PMID- 25578858
TI  - Pre- and post-conditional inhibition of prolyl-4-hydroxylase domain enzymes
      protects the heart from an ischemic insult.
AB  - Several genetically modified mouse models implicated that prolyl-4-hydroxylase
      domain (PHD) enzymes are critical mediators for protecting tissues from an
      ischemic insult including myocardial infarction by affecting the stability and
      activation of hypoxia-inducible factor (HIF)-1 and HIF-2. Thus, the current
      efforts to develop small-molecule PHD inhibitors open a new therapeutic option
      for myocardial tissue protection during ischemia. Therefore, we aimed to
      investigate the applicability and efficacy of pharmacological HIFalpha
      stabilization by a small-molecule PHD inhibitor in the heart. We tested for
      protective effects in the acute phase of myocardial infarction after pre- or post
      conditional application of the inhibitor. Application of the specific PHD
      inhibitor 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate (ICA) resulted
      in HIF-1alpha and HIF-2alpha accumulation in heart muscle cells in vitro and in
      vivo. The rapid and robust responsiveness of cardiac tissue towards ICA was
      further confirmed by induction of the known HIF target genes heme oxygenase-1 and
      PHD3. Pre- and post-conditional treatment of mice undergoing myocardial
      infarction resulted in a significantly smaller infarct size. Tissue protection
      from ischemia after pre- or post-conditional ICA treatment demonstrates that
      there is a therapeutic time window for the application of the PHD inhibitor (PHI)
      post-myocardial infarction, which might be exploited for acute medical
      interventions. 

PMID- 25578859
TI  - Sodium channels in the Cx43 gap junction perinexus may constitute a cardiac
      ephapse: an experimental and modeling study.
AB  - It has long been held that electrical excitation spreads from cell-to-cell in the
      heart via low resistance gap junctions (GJ). However, it has also been proposed
      that myocytes could interact by non-GJ-mediated "ephaptic" mechanisms,
      facilitating propagation of action potentials in tandem with direct GJ-mediated
      coupling. We sought evidence that such mechanisms contribute to cardiac
      conduction. Using super-resolution microscopy, we demonstrate that Nav1.5 is
      localized within 200 nm of the GJ plaque (a region termed the perinexus).
      Electron microscopy revealed close apposition of adjacent cell membranes within
      perinexi suggesting that perinexal sodium channels could function as an ephapse,
      enabling ephaptic cell-to-cell transfer of electrical excitation. Acute
      interstitial edema (AIE) increased intermembrane distance at the perinexus and
      was associated with preferential transverse conduction slowing and increased
      spontaneous arrhythmia incidence. Inhibiting sodium channels with 0.5 MUM
      flecainide uniformly slowed conduction, but sodium channel inhibition during AIE
      slowed conduction anisotropically and increased arrhythmia incidence more than
      AIE alone. Sodium channel inhibition during GJ uncoupling with 25 MUM
      carbenoxolone slowed conduction anisotropically and was also highly
      proarrhythmic. A computational model of discretized extracellular microdomains
      (including ephaptic coupling) revealed that conduction trends associated with
      altered perinexal width, sodium channel conductance, and GJ coupling can be
      predicted when sodium channel density in the intercalated disk is relatively
      high. We provide evidence that cardiac conduction depends on a mathematically
      predicted ephaptic mode of coupling as well as GJ coupling. These data suggest
      opportunities for novel anti-arrhythmic therapies targeting noncanonical
      conduction pathways in the heart.

PMID- 25578860
TI  - Insulin-induced cell division is controlled by the adaptor Grb14 in a Chfr
      dependent manner.
AB  - Beyond its key role in the control of energy metabolism, insulin is also an
      important regulator of cell division and neoplasia. However, the molecular events
      involved in insulin-driven cell proliferation are not fully elucidated. Here, we
      show that the ubiquitin ligase Chfr, a checkpoint protein involved in G2/M
      transition, is a new effector involved in the control of insulin-induced cell
      proliferation. Chfr is identified as a partner of the molecular adapter Grb14, an
      inhibitor of insulin signalling. Using mammalian cell lines and the Xenopus
      oocyte as a model of G2/M transition, we demonstrate that Chfr potentiates the
      inhibitory effect of Grb14 on insulin-induced cell division. Insulin stimulates
      Chfr binding to the T220 residue of Grb14. Both Chfr binding site and Grb14 C-ter
      BPS-SH2 domain, mediating IR binding and inhibition, are required to prevent
      insulin-induced cell division. Targeted mutagenesis revealed that Chfr ligase
      activity and phosphorylation of its T39 residue, a target of Akt, are required to
      potentiate Grb14 inhibitory activity. In the presence of insulin, the binding of
      Chfr to Grb14 activates its ligase activity, leading to Aurora A and Polo-like
      kinase degradation and blocking cell division. Collectively, our results show
      that Chfr and Grb14 collaborate in a negative feedback loop controlling insulin
      stimulated cell division.

PMID- 25578861
TI  - FOXO3a modulates WNT/beta-catenin signaling and suppresses epithelial-to
      mesenchymal transition in prostate cancer cells.
AB  - Emerging evidence has revealed a negative correlation between Forkhead box-O
      (FOXO) expression and prostate cancer grade and spread, indicating its role as a
      suppressor of prostate cancer metastasis. However, there is still incomplete
      understanding about the role of FOXO transcription factors in prostate cancer
      progression. In this investigation, we demonstrate that FOXO3a significantly
      inhibits the expression beta-catenin in prostate cancer cells. The mechanism of
      inhibiting beta-catenin expression involves the FOXO3a-mediated transactivated
      microRNA-34b/c, which consequently suppressed beta-catenin mRNA expression by
      targeting the untranslated regions (UTRs) of beta-catenin. Additionally, FOXO3a
      can directly bind to beta-catenin, and competes with TCF for interaction with
      beta-catenin, thereby inhibiting beta-catenin/TCF transcriptional activity and
      reducing the expression of beta-catenin target genes. Furthermore, prostate
      cancer cells expressing FOXO3a shRNAs display mesenchymal characteristics,
      including enhanced cell migration and differential regulation of the EMT markers,
      whereas knockdown of beta-catenin results in reversal of shFOXO3a-mediated EMT
      phenotypic changes. Collectively, these observations demonstrated that FOXO3a
      inhibits malignant phenotypes that are dependent on beta-catenin-dependent
      modulation of EMT-related genes, and provided fresh insight into the mechanisms
      by which a FOXO3a-miR-34b/c axis restrains canonical beta-catenin signaling
      cascades in prostate cancer cell. 

PMID- 25578863
TI  - Participation of signaling cascades in the regulation of erythropoiesis under
      conditions of cytostatic treatment.
AB  - We studied the role of signaling pathways in the regulation of erythropoiesis
      against the background of myelosuppression caused by administration of 5
      fluorouracil. The important role of cyclic AMP in the maturation of erythroid
      progenitors after cytostatic treatment was demonstrated. The secretory activity
      of myelokaryocytes during the period of erythroid hemopoiesis recovery is mainly
      regulated via the p38 MAPK signaling pathway; non-erythropoietin factors are
      involved in the formation of erythropoietic activity of adherent cells of the
      microenvironment.

PMID- 25578862
TI  - RhoA Kinase (Rock) and p90 Ribosomal S6 Kinase (p90Rsk) phosphorylation of the
      sodium hydrogen exchanger (NHE1) is required for lysophosphatidic acid-induced
      transport, cytoskeletal organization and migration.
AB  - The sodium hydrogen exchanger isoform one (NHE1) plays a critical role
      coordinating asymmetric events at the leading edge of migrating cells and is
      regulated by a number of phosphorylation events influencing both the ion
      transport and cytoskeletal anchoring required for directed migration.
      Lysophosphatidic acid (LPA) activation of RhoA kinase (Rock) and the Ras-ERK
      growth factor pathway induces cytoskeletal reorganization, activates NHE1 and
      induces an increase in cell motility. We report that both Rock I and II
      stoichiometrically phosphorylate NHE1 at threonine 653 in vitro using mass
      spectrometry and reconstituted kinase assays. In fibroblasts expressing NHE1
      alanine mutants for either Rock (T653A) or ribosomal S6 kinase (Rsk; S703A) we
      show that each site is partially responsible for the LPA-induced increase in
      transport activity while NHE1 phosphorylation by either Rock or Rsk at their
      respective site is sufficient for LPA stimulated stress fiber formation and
      migration. Furthermore, mutation of either T653 or S703 leads to a higher basal
      pH level and a significantly higher proliferation rate. Our results identify the
      direct phosphorylation of NHE1 by Rock and suggest that both RhoA and Ras
      pathways mediate NHE1-dependent ion transport and migration in fibroblasts. 

PMID- 25578869
TI  - A prospective randomized phase II study comparing metronomic chemotherapy with
      chemotherapy (single agent cisplatin), in patients with metastatic, relapsed or
      inoperable squamous cell carcinoma of head and neck.
AB  - BACKGROUND: Cetuximab based treatment is the recommended chemotherapy for head
      and neck squamous cell cancers in the palliative setting. However, due to
      financial constraints, intravenous (IV) chemotherapy without cetuximab is
      commonly used in lesser developed countries. We believe that oral metronomic
      chemotherapy may be safer and more effective in this setting. METHODS: We
      conducted an open label, superiority, parallel design, randomized phase II trial
      comparing oral MCT [daily celecoxib (200mg twice daily) and weekly methotrexate
      (15mg/m(2))] to intravenous single agent cisplatin (IP) (75mg/m(2)) given 3
      weekly. Eligible patients had head and neck cancers requiring palliative
      chemotherapy with ECOG PS 0-2 and adequate organ functions who could not afford
      cetuximab. The primary end point was progression-free survival. RESULTS: 110
      Patients were recruited between July 2011 to May 2013, 57 randomized to the MCT
      arm and 53 to the IP arm. Patients in the MCT arm had significantly longer PFS
      (median 101 days, 95% CI: 58.2-143.7 days) compared to the IP arm (median 66
      days, 95% CI; 55.8-76.1 days) (p=0.014). The overall survival (OS) was also
      increased significantly in the MCT arm (median 249 days, 95% CI: 222.5-275.5
      days) compared to the IP arm (median 152 days, 95% CI: 104.2-199.8 days)
      (p=0.02). There were fewer grade 3/4 adverse effects with MCT, which was not
      significant. (18.9% vs. 31.4%, P=0.14). CONCLUSION: Oral metronomic chemotherapy
      has significantly better PFS and OS than single agent platinum in the palliative
      setting.

PMID- 25578870
TI  - The FIGO assessment scoring system (FASS): a new holistic classification tool to
      assess women with pelvic floor dysfunction: validity and reliability.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of our study was to assess the interobserver
      and intraobserver reliability as well as the content and construct validity of
      the FIGO prolapse assessment scoring system (FASS). METHODS: Women with and
      without (controls) symptoms of pelvic organ prolapse (POP) attending gynaecology
      outpatient clinics in four different countries were recruited prospectively. Each
      woman was assessed using the FASS which included: (1) physical examination
      findings designated with the letter P; (2) presence of symptoms of prolapse,
      urinary and bowel symptoms designated with the letter S; and (3) assessment of
      degree of bother designated with the letter B. A scoring system was also
      developed. For interobserver reliability women were examined by two separate
      examiners using the FASS. For intraobserver reliability the FASS was repeated by
      the same examiner within 2 weeks. The interclass correlation coefficient (ICC)
      was also calculated to assess limits of agreements. Validity was assessed by
      comparing the FASS scores between symptomatic and asymptomatic women using the
      Mann-Whitney U test (p value <0.001). RESULTS: A total of 177 women (98
      symptomatic and 79 controls) were recruited. Intraobserver reliability had ICCs
      between 0.716 and 1. Interobserver reliability had ICCs between 0.795 and 0.909.
      Domain and total scores were significantly different between symptomatic and
      asymptomatic women (p < 0.001, Mann-Whitney U test). There was a good correlation
      between FASS P scores and POP-Q scores (rho 0.763, p < 0.001). CONCLUSIONS: The
      FIGO prolapse assessment scoring system has good intraobserver and interobserver
      agreement and has demonstrated both content and construct validity.

PMID- 25578871
TI  - The Manchester-Fothergill and the Elevate Posterior technique for the correction
      of a cervical elongation and large enterocele in a patient with bladder exstrophy
      and multiple surgeries.
AB  - INTRODUCTION AND HYPOTHESIS: A 60-year-old woman presented with congenital
      bladder exstrophy, urinary incontinence since birth, and pelvic organ prolapse
      since the menopause at the age of 46 years. METHODS: The patient (gravida 2, para
      2 by cesarean sections and tubal ligation) described an extensive past surgical
      history that included epispadias and neourethral procedures, anti-reflux surgery
      using the Lich-Gregoir technique, bilateral ureterosigmoidostomy achieving
      continence, uterine fixation after the Doleris operation, and neovaginal
      reconstruction. The physical examination revealed a fourth-degree enterocele with
      cervical elongation (POP-Q: Aa-2, Ba-2, C + 3, D + 4, gh:5, pb:2.5, Tvl:6, Ap +
      3, Bp +6). Gynecological ultrasound and uro-CT were performed to ensure that the
      ureterosigmoidostomy had been successful, and CT-based 3D bone reconstructions
      were obtained to calculate the distance between the pubic rami and the ischial
      spines. Based on a literature review of the management options for these patients
      and the specific characteristics of our patient, a decision was made to perform
      trachelectomy (the Manchester technique with Fothergill stitches) and a
      polypropylene mesh placement with sacrospinous ligament anchor (Elevate
      Posterior(r) PC, AMS). RESULTS: Six months after the surgery, we observed good
      anatomical and functional results with significant improvement in the patient's
      quality-of-life scale score. CONCLUSION: We believed that the vaginal approach
      was minimally invasive with a low risk of morbidity in our patient, who had a
      very altered anatomy, but produced a satisfactory functional result.

PMID- 25578872
TI  - Patient-focused websites related to stress urinary incontinence and pelvic organ
      prolapse: a DISCERN quality analysis.
AB  - INTRODUCTION AND HYPOTHESIS: The quality of information related to pelvic floor
      disorders is varied and understudied. Using a validated instrument we evaluated
      the quality of selected websites addressing treatment options for pelvic organ
      prolapse (POP) and stress urinary incontinence (SUI). METHODS: English-language,
      patient-focused professional, governmental, and consumer websites related to POP
      and SUI were identified using the International Urogynecology Association (IUGA)
      list of continence societies worldwide, search terms, and provider nomination.
      Websites were evaluated by 10 providers at an academic medical center,
      representing urogynecology (6), urology (3), and general gynecology (1). Quality
      assessment utilized the DISCERN instrument, a validated instrument consisting of
      16 questions addressing the quality of consumer health information. RESULTS:
      Websites of 13 organizations met inclusion criteria and were assessed, 12
      relating to SUI and 8 to POP. The websites with the highest mean total DISCERN
      score for POP were those of the IUGA, the American Society of Colon and Rectal
      Surgeons, and the American Urogynecologic Association, and for SUI, the National
      Association For Continence, the American Urological Association, and the IUGA.
      High correlations were obtained for the total DISCERN score and the overall
      quality scores for POP (0.76) and SUI (0.82). The most commonly omitted
      components of the DISCERN instrument were a clear statement of the content
      objectives, references or sources of the content, and a discussion of what
      patients could expect if they opted for no intervention. CONCLUSIONS: Available
      English-language professional websites written to inform patients about
      management choices for SUI and POP miss key components of quality patient
      information.

PMID- 25578875
TI  - Structure and assembly pathway of the ribosome quality control complex.
AB  - During ribosome-associated quality control, stalled ribosomes are split into
      subunits and the 60S-housed nascent polypeptides are poly-ubiquitinated by
      Listerin. How this low-abundance ubiquitin ligase targets rare stall-generated
      60S among numerous empty 60S is unknown. Here, we show that Listerin specificity
      for nascent chain-60S complexes depends on nuclear export mediator factor (NEMF).
      The 3.6 A cryo-EM structure of a nascent chain-containing 60S-Listerin-NEMF
      complex revealed that NEMF makes multiple simultaneous contacts with 60S and
      peptidyl-tRNA to sense nascent chain occupancy. Structural and mutational
      analyses showed that ribosome-bound NEMF recruits and stabilizes Listerin's N
      terminal domain, while Listerin's C-terminal RWD domain directly contacts the
      ribosome to position the adjacent ligase domain near the nascent polypeptide exit
      tunnel. Thus, highly specific nascent chain targeting by Listerin is imparted by
      the avidity gained from a multivalent network of context-specific individually
      weak interactions, highlighting a new principle of client recognition during
      protein quality control. 

PMID- 25578876
TI  - Global and specific responses of the histone acetylome to systematic
      perturbation.
AB  - Regulation of histone acetylation is fundamental to the utilization of eukaryotic
      genomes in chromatin. Aberrant acetylation contributes to disease and can be
      clinically combated by inhibiting the responsible enzymes. Our knowledge of the
      histone acetylation system is patchy because we so far lacked the methodology to
      describe acetylation patterns and their genesis by integrated enzyme activities.
      We devised a generally applicable, mass spectrometry-based strategy to precisely
      and accurately quantify combinatorial modification motifs. This was applied to
      generate a comprehensive inventory of acetylation motifs on histones H3 and H4 in
      Drosophila cells. Systematic depletion of known or suspected acetyltransferases
      and deacetylases revealed specific alterations of histone acetylation signatures,
      established enzyme-substrate relationships, and unveiled an extensive crosstalk
      between neighboring modifications. Unexpectedly, overall histone acetylation
      levels remained remarkably constant upon depletion of individual
      acetyltransferases. Conceivably, the acetylation level is adjusted to maintain
      the global charge neutralization of chromatin and the stability of nuclei. 

PMID- 25578877
TI  - Locus-specific targeting to the X chromosome revealed by the RNA interactome of
      CTCF.
AB  - CTCF is a master regulator that plays important roles in genome architecture and
      gene expression. How CTCF is recruited in a locus-specific manner is not fully
      understood. Evidence from epigenetic processes, such as X chromosome inactivation
      (XCI), indicates that CTCF associates functionally with RNA. Using genome-wide
      approaches to investigate the relationship between its RNA interactome and
      epigenomic landscape, here we report that CTCF binds thousands of transcripts in
      mouse embryonic stem cells, many in close proximity to CTCF's genomic binding
      sites. CTCF is a specific and high-affinity RNA-binding protein (Kd < 1 nM).
      During XCI, CTCF differentially binds the active and inactive X chromosomes and
      interacts directly with Tsix, Xite, and Xist RNAs. Tsix and Xite RNAs target CTCF
      to the X inactivation center, thereby inducing homologous X chromosome pairing.
      Our work elucidates one mechanism by which CTCF is recruited in a locus-specific
      manner and implicates CTCF-RNA interactions in long-range chromosomal
      interactions. 

PMID- 25578878
TI  - Developmental control of polycomb subunit composition by GATA factors mediates a
      switch to non-canonical functions.
AB  - Polycomb repressive complex 2 (PRC2) plays crucial roles in transcriptional
      regulation and stem cell development. However, the context-specific functions
      associated with alternative subunits remain largely unexplored. Here we show that
      the related enzymatic subunits EZH1 and EZH2 undergo an expression switch during
      blood cell development. An erythroid-specific enhancer mediates transcriptional
      activation of EZH1, and a switch from GATA2 to GATA1 controls the developmental
      EZH1/2 switch by differential association with EZH1 enhancers. We further examine
      the in vivo stoichiometry of the PRC2 complexes by quantitative proteomics and
      reveal the existence of an EZH1-SUZ12 subcomplex lacking EED. EZH1 together with
      SUZ12 form a non-canonical PRC2 complex, occupy active chromatin, and positively
      regulate gene expression. Loss of EZH2 expression leads to repositioning of EZH1
      to EZH2 targets. Thus, the lineage- and developmental stage-specific regulation
      of PRC2 subunit composition leads to a switch from canonical silencing to non
      canonical functions during blood stem cell specification. 

PMID- 25578879
TI  - PI(5)P regulates autophagosome biogenesis.
AB  - Phosphatidylinositol 3-phosphate (PI(3)P), the product of class III PI3K VPS34,
      recruits specific autophagic effectors, like WIPI2, during the initial steps of
      autophagosome biogenesis and thereby regulates canonical autophagy. However,
      mammalian cells can produce autophagosomes through enigmatic noncanonical VPS34
      independent pathways. Here we show that PI(5)P can regulate autophagy via PI(3)P
      effectors and thereby identify a mechanistic explanation for forms of
      noncanonical autophagy. PI(5)P synthesis by the phosphatidylinositol 5-kinase
      PIKfyve was required for autophagosome biogenesis, and it increased levels of
      PI(5)P, stimulated autophagy, and reduced the levels of autophagic substrates.
      Inactivation of VPS34 impaired recruitment of WIPI2 and DFCP1 to autophagic
      precursors, reduced ATG5-ATG12 conjugation, and compromised autophagosome
      formation. However, these phenotypes were rescued by PI(5)P in VPS34-inactivated
      cells. These findings provide a mechanistic framework for alternative VPS34
      independent autophagy-initiating pathways, like glucose starvation, and unravel a
      cytoplasmic function for PI(5)P, which previously has been linked predominantly
      to nuclear roles. 

PMID- 25578881
TI  - Dalbavancin (BI-387) for the treatment of complicated skin and skin structure
      infection.
AB  - In the era of increasing antibiotic resistance, development of new agents that
      could provide therapeutic options for difficult to treat pathogens is vital.
      Dalbavancin is a new lipoglycopeptide recently approved by the US FDA for the
      treatment of acute bacterial skin and skin structure infections. A derivative of
      the older glycopeptide class, chemical structure alterations resulted in a
      molecule with a similar mechanism of action, however, with a comparatively
      increased activity as reflected by organism MICs. These modifications also
      resulted in an antibiotic with distinctive properties that allow for once-weekly
      dosing in the treatment of Gram-positive pathogens, including methicillin
      resistant Staphylococcus aureus and drug resistant Streptococcus spp. As the
      first of these long acting compounds, understanding the pharmacokinetic and
      pharmacodynamic properties of agents like dalbavancin is essential for
      determining a place in therapy. 

PMID- 25578880
TI  - Cold-inducible Zfp516 activates UCP1 transcription to promote browning of white
      fat and development of brown fat.
AB  - Uncoupling protein 1 (UCP1) mediates nonshivering thermogenesis and, upon cold
      exposure, is induced in brown adipose tissue (BAT) and subcutaneous white adipose
      tissue (iWAT). Here, by high-throughput screening using the UCP1 promoter, we
      identify Zfp516 as a transcriptional activator of UCP1 as well as PGC1alpha,
      thereby promoting a BAT program. Zfp516 itself is induced by cold and sympathetic
      stimulation through the cAMP-CREB/ATF2 pathway. Zfp516 directly binds to the
      proximal region of the UCP1 promoter, not to the enhancer region where other
      transcription factors bind, and interacts with PRDM16 to activate the UCP1
      promoter. Although ablation of Zfp516 causes embryonic lethality, knockout
      embryos still show drastically reduced BAT mass. Overexpression of Zfp516 in
      adipose tissue promotes browning of iWAT even at room temperature, increasing
      body temperature and energy expenditure and preventing diet-induced obesity.
      Zfp516 may represent a future target for obesity therapeutics. 

PMID- 25578883
TI  - Management of severe non-TB bacterial infection in HIV-infected adults.
AB  - Despite widespread antiretroviral therapy use, severe bacterial infections (SBI)
      in HIV-infected adults continue to cause significant morbidity and mortality
      globally. Four main pathogens account for the majority of documented SBI:
      Streptococcus pneumoniae, non-typhoidal strains of Salmonella enterica,
      Escherichia coli and Staphylococcus aureus. The epidemiology of SBI is dynamic,
      both in developing countries where, despite dramatic successes in antiretroviral
      therapy, coverage is far from complete, and in settings in both resource-poor and
      resource-rich countries where antiretroviral therapy failure is becoming
      increasingly common. Throughout the world, this complexity is further compounded
      by rapidly emerging antimicrobial resistance, making management of SBI very
      challenging in these vulnerable patients. We review the causes and treatment of
      SBI in HIV-infected people and discuss future developments in this field.

PMID- 25578884
TI  - Novel pandemic influenza A (H1N1) and community-associated methicillin-resistant
      Staphylococcus aureus pneumonia.
AB  - Postinfluenza bacterial pneumonia is a leading cause of influenza-associated
      death, and Staphylococcus aureus and Streptococcus pneumoniae have been important
      pathogens that have caused pneumonia since the influenza pandemic in 1919.
      Emergence of novel influenza A (H1N1) pdm09 and the concomitant global spread of
      community-associated methicillin-resistant S. aureus (CA-MRSA) have led to
      increasing prevalence of CA-MRSA pneumonia following influenza infection. Such an
      epidemiologic change poses a therapeutic challenge due to a high risk of
      inappropriate empiric antimicrobial therapy and poor clinical outcomes. Early
      diagnosis and initiation of appropriate antimicrobial therapy for post-influenza
      bacterial pneumonia have become even more important in the era of CA-MRSA.
      Therefore, novel molecular diagnostic techniques should be applied to more
      readily diagnose MRSA pneumonia. 

PMID- 25578882
TI  - Prevention of mother-to-child transmission of HIV type 1: the role of neonatal
      and infant prophylaxis.
AB  - The prevention of mother-to-child transmission (PMTCT) of HIV is one of the great
      public health successes of the past 20 years. Much concerted research efforts and
      dedicated work have led to the achievement of very low rates of PMTCT of HIV in
      settings that can implement optimal prophylaxis. Though several implementation
      challenges remain, global elimination of pediatric HIV infection seems now more
      than ever to be an attainable goal. Often overlooked, the role of prophylaxis of
      the newborn is nevertheless a very important component of PMTCT. In this paper,
      we focus on the role of neonatal and infant prophylaxis, discuss mechanisms of
      protection, and present the clinical trial-generated evidence that led to the
      current recommendations for preventing infections in breastfed and non-breastfed
      infants. PMTCT of HIV should not end at birth; a continuum of care extending
      postpartum and postnatally is required to minimize the risk of new pediatric HIV
      infections.

PMID- 25578885
TI  - Neonatal CNS infection and inflammation caused by Ureaplasma species: rare or
      relevant?
AB  - Colonization with Ureaplasma species has been associated with adverse pregnancy
      outcome, and perinatal transmission has been implicated in the development of
      bronchopulmonary dysplasia in preterm neonates. Little is known about Ureaplasma
      mediated infection and inflammation of the CNS in neonates. Controversy remains
      concerning its incidence and implication in the pathogenesis of neonatal brain
      injury. In vivo and in vitro data are limited. Despite improving care options for
      extremely immature preterm infants, relevant complications remain. Systematic
      knowledge of ureaplasmal infection may be of great benefit. This review aims to
      summarize pathogenic mechanisms, clinical data and diagnostic pitfalls. Studies
      in preterm and term neonates are critically discussed with regard to their
      limitations. Clinical questions concerning therapy or prophylaxis are posed. We
      conclude that ureaplasmas may be true pathogens, especially in preterm neonates,
      and may cause CNS inflammation in a complex interplay of host susceptibility,
      serovar pathogenicity and gestational age-dependent CNS vulnerability. 

PMID- 25578886
TI  - An update on surgical and antimicrobial therapy for acute periprosthetic joint
      infection: new challenges for the present and the future.
AB  - Periprosthetic joint infection (PJI) is a devastating complication that can occur
      following any arthroplasty procedure. Approximately half of these infections
      develop within the first year after arthroplasty, mainly in the first 1 to 3
      months. These infections are known as early PJI. It is widely accepted that many
      early PJIs can be successfully managed by debridement, irrigation, and prosthetic
      retention, followed by a course of biofilm-effective antibiotics (debridement,
      antibiotics, implant retention procedure), but candidate patients should meet the
      requirements set down in Zimmerli's algorithm. The best antibiotic regimen for
      acute PJI treated without implant removal remains uncertain. Rifampin-containing
      regimens, when feasible, are recommended in gram-positive infections, and
      fluoroquinolones in gram-negative cases. The duration, dosage, and administration
      route of antibiotics and the use of combined therapy are matters that requires
      further clarification, as the current level of evidence is low and most
      recommendations are based on experimental data, studies in small series, and
      expert experience.

PMID- 25578887
TI  - Managing Nontraumatic Acute Back Pain.

PMID- 25578888
TI  - The Many Faces of Survivor Bias in Observational Studies on Trauma Resuscitation
      Requiring Massive Transfusion.

PMID- 25578889
TI  - Applications of Important Polysaccharides in Drug Delivery.
AB  - Polysaccharide is a kind of biological material, which has good biocompatibility,
      non-toxicity, and non-immunogenicity. So, the polysaccharide has widely been
      applied in drug delivery system. The applications of chitosan, hyaluronic acid
      and dextran in drug delivery have been summarized herein. 

PMID- 25578890
TI  - Sarcosine-Based Glycine Transporter Type-1 (GlyT-1) Inhibitors Containing
      Pyridazine Moiety: A Further Search for Drugs with Potential to Influence
      Schizophrenia Negative Symptoms.
AB  - We have synthesized a novel series of N-substituted sarcosines, analogues of NFPS
      (N-[3-(biphenyl-4- yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine), as type-1
      glycine transporter (GlyT-1) inhibitors. Several compounds incorporated a diazine
      ring inhibited recombinant hGlyT-1b expressed permanently in CHO cells and GlyT-1
      in rat brain synaptosomal preparations. A structure-activity relationship for the
      newly synthesized compounds was obtained and discussed on the ground of their
      GlyT-1 inhibitory potencies. Replacement of the biphenyl-4-yloxy moiety in NFPS
      with a 5-pyridazinylphenoxy moiety (compounds 3, 4, 5, and 6) or a 2-phenyl-5-
      pyridazinyloxy moiety (compounds 10, 11, and 12) afforded compounds exhibiting
      potent inhibition on GlyT-1 activity. The GlyT-1 inhibitory properties of NFPS
      analogues, in which sarcosine was closed into a ring forming
      (methylamino)pyridazine-3-(2H)-one, were markedly reduced (compounds 13 and 14).
      The pyridazine-containing GlyT-1 inhibitors with in vitro GlyT-1 inhibitory
      potency also enhanced extracellular glycine concentrations in conscious rat
      striatum as was measured by microdialysis technique. In contrast to NFPS,
      sarcosine-based pyridazine containing GlyT-1 inhibitors failed to evoke
      compulsive running behavior whereas they inhibited phencyclidine- induced
      hypermotility in mice. It is believed that increase of extracellular
      concentrations of glycine by inhibition of its reuptake may probably influence
      positively glutamate N-methyl-D-aspartate (NMDA)-type ionotropic receptors in the
      central nervous system. This may have importance in the treatment of
      neuropsychiatric disorders associated with hypofunctional NMDA receptor-mediated
      glutamatergic neurochemical transmission. Thus, impaired NMDA receptor functions
      have been shown to be involved in the development of the negative symptoms and
      the cognitive deficit of schizophrenia and the treatment of these symptoms is the
      possible clinical indication of GlyT-1 inhibitors including those containing
      pyridazine moiety. 

PMID- 25578891
TI  - Application of molecular imaging technologies in antitumor drug development and
      therapy.
AB  - Molecular imaging enables noninvasive characterization, quantification and
      visualization of biological and pathological processes in vivo at cellular and
      molecular level. It plays an important role in drug discovery and development.
      The skillful use of molecular imaging can provide unique insights into disease
      processes, which greatly aid in identifications of target. Importantly, molecular
      imaging is widely applied in the pharmacodynamics study to provide earlier
      endpoints during the preclinical drug development process, since it can be
      applied to monitor the effects of treatment in vivo with the use of biomarkers.
      Herein, we reviewed the application of molecular imaging technologies in
      antitumor drug development process ranging from identification of targets to
      evaluation of therapeutic effect. 

PMID- 25578892
TI  - Deoxynivalenol induces cytotoxicity and genotoxicity in animal primary cell
      culture.
AB  - Deoxynivalenol (DON), a mycotoxin produced by Fusarium graminearum, is widely
      found as a contaminant of food. DON is responsible for a wide range of toxic
      activities, including gastro-intestinal, lymphoid, bone-marrow and
      cardiotoxicity. But, the complete explorations of toxicity in terms of
      hepatotoxicity, nephrotoxicity, cytotoxicity and genotoxicity as well have not
      been documented well. Again, the mechanisms through which DON damages the DNA and
      promotes cellular toxicity are not well established. Considering the above fact,
      this research article is focused on the effects of DON-induced toxicities on
      experimental animal model as well as its effects on cellular level via various
      toxicological investigations. DON treatment showed cytotoxicity and DNA damage.
      Further, flow cytometric analysis of hepatocytes showed cellular apoptosis,
      suggesting that DON-induced hepatotoxicity is, may be partly, mediated by
      apoptosis. Moreover, significant differences were found in each haematology and
      clinical chemistry value, either (p > 0.05). No abnormality of any organ was
      found during histopathological examination. Hence, it can be concluded that DON
      induces oxidative DNA damage and increases the formation of centromere positive
      micronuclei due to aneugenic activity.

PMID- 25578896
TI  - Organ-specific antibodies in first-degree relatives of patients with type 2
      diabetes.

PMID- 25578897
TI  - Investigation and analysis of microbiological communities in natural
      Ophiocordyceps sinensis.
AB  - Ophiocordyceps sinensis is a fungus that parasitizes caterpillars, and more than
      30 species of filamentous fungi have been isolated from its fruiting body.
      However, its microbiological diversity remains unclear. Based on the clone
      library and quantitative PCR techniques, the bacterial flora and mycobiota of 3
      different samples (larva, stromata/sclerotia, and surface soil) from natural O.
      sinensis specimens were investigated using primer sets that targeted the 16S rRNA
      gene and internal transcribed spacer region of ribosomal DNA. The results showed
      that the abundance of bacterial and fungal communities in the soil attached to
      the surface of O. sinensis was (6.4 +/- 1.4) * 10(6) and (6.0 +/- 0.3) * 10(7)
      copies/g dry matter, respectively, which was the highest compared with that in
      the larva and stromal samples. The main groups of bacteria in the O. sinensis
      samples were Proteobacteria and Actinobacteria, while Ascomycota was the most
      dominant fungal group in the 3 samples. At the genus level, Geomyces, Phoma, and
      Trichocladium were the dominant genera in the larval sample, while Geomyces and
      Cladosporium were the dominant genera in the stromal sample. In conclusion, a
      great number of bacterial and fungal species were present in naturally occurring
      O. sinensis specimens, and there was a high diversity of bacterial and fungal
      communities. These findings contribute to the understanding of the bacterial and
      fungal community structure of this valuable medicinal fungus and lay the
      foundation for the future discovery of new medicinal microorganism resources. 

PMID- 25578900
TI  - Bayesian analysis of additive epistasis arising from new mutations in mice.
AB  - The continuous uploading of polygenic additive mutational variability has been
      reported in several studies in laboratory species with an inbred genetic
      background. These studies have focused on the direct contribution of new
      mutations without considering the possibility of epistatic effects derived from
      the interaction of new mutations with pre-existing polymorphisms. In this work we
      focused on this main topic and analysed the statistical and biological relevance
      of the epistatic variance for 9 week body weight in two populations of inbred
      mice. We developed a new linear mixed model parameterization where founder
      related additive genetic variability, additive mutational variability and the
      interaction terms between both sources of variation were accounted for under a
      Bayesian design and without requiring the inversion of a matrix of epistatic
      genetic covariances. The analyses focused on a six-generations data set from
      C57BL/6J mice (n = 3736) and a five-generations data set from C57BL/6J(hg/hg)
      mice (n = 2843). The deviance information criterion (DIC) clearly favoured the
      model accounting for epistatic variability with reductions larger than 50 DIC
      units in both populations. Modal estimates for founder related, mutational and
      epistatic heritabilities were 0.068, 0.011 and 0.095 in C57BL/6J and 0.060, 0.010
      and 0.113 in C57BL/6J(hg/hg), ruling out any doubt about the biological relevance
      of epistasis originating from new mutations in mice. These results contribute new
      insights on the relevance of epistasis in the genetic architecture of mammals and
      serve as an important component of an additional source of genetic heterogeneity
      for inbred strains of laboratory mice.

PMID- 25578901
TI  - Characteristics of scratching behavior in ADJM mice (atopic dermatitis from
      Japanese mice).
AB  - In order to elucidate the characteristics of scratching behavior in atopic
      dermatitis from Japanese mice (ADJM) mice, the effects of some antagonists of
      pruritogens on this behavior were studied. Both male and female ADJM mice showed
      frequent scratching behavior around the face, abdomen and back. The number of
      scratching behavior around the face was greater than on the abdomen and back, and
      scratching behavior in female mice was significantly more frequent than in male
      mice. Histamine H1 antagonist, chlorpheniramine, p.o., inhibited this behavior
      potently and dose-dependently. Histamine H1 antagonist with serotonin 5-TH(5
      hydroxytryptamine)2 antagonist, cyproheptadine, also inhibited this behavior.
      However, NK1 antagonist, aprepitant, p.o., had no significant inhibitory effect
      even at a dose of 100 mg/kg, p.o., Mu antagonist, naloxone, and kappa agonist,
      nalfurafine, significantly inhibited this behavior at doses of 0.3 mg/kg, s.c.,
      and 0.01 mg/kg, p.o., respectively. Histamine contents in the skin of ADJM mice
      were significantly higher than in BALB/c mice. These results strongly indicate
      that scratching behavior in ADJM mice is related with histamine H1, opioid mu and
      opioid kappa receptors. 

PMID- 25578899
TI  - Solid-state NMR of the Yersinia pestis outer membrane protein Ail in lipid
      bilayer nanodiscs sedimented by ultracentrifugation.
AB  - Solid-state NMR studies of sedimented soluble proteins has been developed
      recently as an attractive approach for overcoming the size limitations of
      solution NMR spectroscopy while bypassing the need for sample crystallization or
      precipitation (Bertini et al. Proc Natl Acad Sci USA 108(26):10396-10399, 2011).
      Inspired by the potential benefits of this method, we have investigated the
      ability to sediment lipid bilayer nanodiscs reconstituted with a membrane
      protein. In this study, we show that nanodiscs containing the outer membrane
      protein Ail from Yersinia pestis can be sedimented for solid-state NMR structural
      studies, without the need for precipitation or lyophilization. Optimized
      preparations of Ail in phospholipid nanodiscs support both the structure and the
      fibronectin binding activity of the protein. The same sample can be used for
      solution NMR, solid-state NMR and activity assays, facilitating structure
      activity correlation experiments across a wide range of timescales. 

PMID- 25578902
TI  - Novel screening methods--biosensors.
AB  - Biosensors offer exciting possibilities for improving cells or enzymes as
      biocatalysts for the synthesis of small molecules. We here review recent progress
      in the development and the screening applications of transcription-factor-based
      biosensors. An example is a cofactor-dependent biosensor which provides a
      generalizable screen for NADPH-dependent enzymes. Another example is the use of a
      biosensor in combination with recombineering for strain development, thereby
      expanding the genome engineering techniques to deliver directly bacteria
      producing small molecules of interest. Biosensor-based techniques in combination
      with fluorescence-activated cell sorting demonstrate that the gap regarding
      throughput capabilities of existing methods for the generation of genetic
      diversity and methods for the subsequent screening can be closed. 

PMID- 25578903
TI  - Contrasting specializations for facial motion within the macaque face-processing
      system.
AB  - Facial motion transmits rich and ethologically vital information, but how the
      brain interprets this complex signal is poorly understood. Facial form is
      analyzed by anatomically distinct face patches in the macaque brain, and facial
      motion activates these patches and surrounding areas. Yet, it is not known
      whether facial motion is processed by its own distinct and specialized neural
      machinery, and if so, what that machinery's organization might be. To address
      these questions, we used fMRI to monitor the brain activity of macaque monkeys
      while they viewed low- and high-level motion and form stimuli. We found that,
      beyond classical motion areas and the known face patch system, moving faces
      recruited a heretofore unrecognized face patch. Although all face patches
      displayed distinctive selectivity for face motion over object motion, only two
      face patches preferred naturally moving faces, while three others preferred
      randomized, rapidly varying sequences of facial form. This functional divide was
      anatomically specific, segregating dorsal from ventral face patches, thereby
      revealing a new organizational principle of the macaque face-processing system.

PMID- 25578904
TI  - Collective cell motility promotes chemotactic prowess and resistance to
      chemorepulsion.
AB  - Collective cell migration is a widespread biological phenomenon, whereby groups
      of highly coordinated, adherent cells move in a polarized fashion. This migration
      mode is a hallmark of tissue morphogenesis during development and repair and of
      solid tumor dissemination. In addition to circulating as solitary cells, lymphoid
      malignancies can assemble into tissues as multicellular aggregates. Whether
      malignant lymphocytes are capable of coordinating their motility in the context
      of chemokine gradients is, however, unknown. Here, we show that, upon exposure to
      CCL19 or CXCL12 gradients, malignant B and T lymphocytes assemble into clusters
      that migrate directionally and display a wider chemotactic sensitivity than
      individual cells. Physical modeling recapitulates cluster motility statistics and
      shows that intracluster cell cohesion results in noise reduction and enhanced
      directionality. Quantitative image analysis reveals that cluster migration runs
      are periodically interrupted by transitory rotation and random phases that favor
      leader cell turnover. Additionally, internalization of CCR7 in leader cells is
      accompanied by protrusion retraction, loss of polarity, and the ensuing
      replacement by new leader cells. These mechanisms ensure sustained forward
      migration and resistance to chemorepulsion, a behavior of individual cells
      exposed to steep CCL19 gradients that depends on CCR7 endocytosis. Thus,
      coordinated cluster dynamics confer distinct chemotactic properties, highlighting
      unexpected features of lymphoid cell migration.

PMID- 25578905
TI  - The role of age-specific learning and experience for turtles navigating a
      changing landscape.
AB  - The severity of the environment often influences animal cognition [1-6], as does
      the rate of change within that environment [7-10]. Rapid alteration of habitat
      places limitations on basic resources such as energy, water, nesting sites, and
      refugia [8, 10]. How animals respond to these situations provides insight into
      the mechanisms of cognition and the role of behavior in adaptation [11-13]. We
      tested the hypothesis that learning plays a role in the navigation of the painted
      turtle (Chrysemys picta) within a model of environmental change. We radiotracked
      experienced and naive turtles at different developmental stages from two
      different populations as they sought out new habitats when their pond was
      destroyed. Our data suggest that the ability of turtles to navigate is
      facilitated in part by experience during a critical period. Resident adults
      repeatedly used specific routes with exceptional precision, while translocated
      adults failed to find water. Naive juveniles (1-3 years old) from both
      populations used the same paths taken by resident adults; the ability to follow
      paths was lost by age 4. We also used laboratory behavioral assays to examine the
      possible cues facilitating this precise navigation. Turtles responded to
      manipulation of the local ultraviolet environment, but not the olfactory
      environment. This is the first evidence to suggest that learning during a
      critical period may be important for how animals respond to changing
      environments. Our work emphasizes the need for the examination of learning in
      navigation and the breadth of critical learning periods across vertebrates. 

PMID- 25578906
TI  - The vomeronasal system mediates sick conspecific avoidance.
AB  - Although sociability offers many advantages, a major drawback is the increased
      risk of exposure to contagious pathogens, like parasites, viruses, or bacteria.
      Social species have evolved various behavioral strategies reducing the
      probability of pathogen exposure. In rodents, sick conspecific avoidance can be
      induced by olfactory cues emitted by parasitized or infected conspecifics. The
      neural circuits involved in this behavior remain largely unknown. We observed
      that olfactory cues present in bodily products of mice in an acute inflammatory
      state or infected with a viral pathogen are aversive to conspecifics. We found
      that these chemical signals trigger neural activity in the vomeronasal system, an
      olfactory subsystem controlling various innate behaviors. Supporting the
      functional relevance of these observations, we show that preference toward
      healthy individuals is abolished in mice with impaired vomeronasal function.
      These findings reveal a novel function played by the vomeronasal system.

PMID- 25578907
TI  - The value of the follow-through derives from motor learning depending on future
      actions.
AB  - In ball sports, we are taught to follow through, despite the inability of events
      after contact or release to influence the outcome [1, 2]. Here we show that the
      specific motor memory active at any given moment critically depends on the
      movement that will be made in the near future. We demonstrate that associating a
      different follow-through movement with two motor skills that normally interfere
      [3-7] allows them to be learned simultaneously, suggesting that distinct future
      actions activate separate motor memories. This implies that when learning a
      skill, a variable follow-through would activate multiple motor memories across
      practice, whereas a consistent follow-through would activate a single motor
      memory, resulting in faster learning. We confirm this prediction and show that
      such follow-through effects influence adaptation over time periods associated
      with real-world skill learning. Overall, our results indicate that movements made
      in the immediate future influence the current active motor memory. This suggests
      that there is a critical time period both before [8] and after the current
      movement that determines motor memory activation and controls learning. 

PMID- 25578908
TI  - Mirror-induced self-directed behaviors in rhesus monkeys after visual
      somatosensory training.
AB  - Mirror self-recognition is a hallmark of higher intelligence in humans. Most
      children recognize themselves in the mirror by 2 years of age. In contrast to
      human and some great apes, monkeys have consistently failed the standard mark
      test for mirror self-recognition in all previous studies. Here, we show that
      rhesus monkeys could acquire mirror-induced self-directed behaviors resembling
      mirror self-recognition following training with visual-somatosensory association.
      Monkeys were trained on a monkey chair in front of a mirror to touch a light spot
      on their faces produced by a laser light that elicited an irritant sensation.
      After 2-5 weeks of training, monkeys had learned to touch a face area marked by a
      non-irritant light spot or odorless dye in front of a mirror and by a virtual
      face mark on the mirroring video image on a video screen. Furthermore, in the
      home cage, five out of seven trained monkeys showed typical mirror-induced self
      directed behaviors, such as touching the mark on the face or ear and then looking
      at and/or smelling their fingers, as well as spontaneously using the mirror to
      explore normally unseen body parts. Four control monkeys of a similar age that
      went through mirror habituation but had no training of visual-somatosensory
      association did not pass any mark tests and did not exhibit mirror-induced self
      directed behaviors. These results shed light on the origin of mirror self
      recognition and suggest a new approach to studying its neural mechanism.

PMID- 25578909
TI  - Bats aggregate to improve prey search but might be impaired when their density
      becomes too high.
AB  - Social foraging is a very common yet extremely complex behavior. Numerous studies
      attempted to model it with little supporting evidence. Studying it in the wild is
      difficult because it requires monitoring the animal's movement, its foraging
      success, and its interactions with conspecifics. We present a novel system that
      enables full night ultrasonic recording of freely foraging bats, in addition to
      GPS tracking. As they rely on echolocation, audio recordings of bats allow
      tapping into their sensory acquisition of the world. Rapid changes in
      echolocation allowed us to reveal the bats' dynamic reactions in response to prey
      or conspecifics-two key behaviors that are extremely difficult to assess in most
      animals. We found that bats actively aggregate and forage as a group. However, we
      also found that when the group became too dense, bats were forced to devote
      sensory attention to conspecifics that frequently entered their biosonar "field
      of view," impairing the bats' prey detection performance. Why then did bats fly
      in such high densities? By emitting echolocation calls, bats constantly provide
      public information about their detection of prey. Bats could therefore benefit
      from intentionally flying at a distance that enables eavesdropping on
      conspecifics. Group foraging, therefore, probably allowed bats to effectively
      operate as an array of sensors, increasing their searching efficiency. We suggest
      that two opposing forces are at play in determining the efficient foraging
      density: on the one hand, higher densities improve prey detection, but on the
      other hand, they increase conspecific interference.

PMID- 25578914
TI  - Estrogen replacement improves skeletal muscle performance by increasing
      parvalbumin levels in ovariectomized rats.
AB  - Muscle weakness is common during menopause. Effective estrogen replacement was
      hypothesized to prevent sarcopenia. This study aimed to investigate the estrogen
      level, estrogen receptors (alpha and beta) immunoreactivities, muscle mass and
      functions, and parvalbumin (PV) levels in the extensor digitorum longus (EDL) and
      the gastrocnemius muscles of ovariectomized rats. Adult female Wistar rats (12
      weeks old) were divided into five groups: sham-operated (SHAM), and
      ovariectomized (E0) groups that received 10 weeks of estrogen replacements of
      0MUg/kg (E0), 10MUg/kg (E10), 20MUg/kg (E20) and 40MUg/kg (E40). The estrogen
      levels, ER alpha and ER beta immunoreactivities, muscle fiber sizes and
      contractivities and the PV levels were reduced in the E0 group, but increased in
      all the estrogen replacement groups in both muscles. This study indicated that
      the reduction of estrogen levels led to a decrease of both ER alpha and ER beta
      resulting in a decline in muscle mass and PV levels. The decrease of PV levels
      affected muscle performance, whereas estrogen replacement increased both the ER
      alpha and ER beta. The increase in the PV levels may result in an improvement of
      muscle performance. This may explain one mechanism of estrogen on muscle mass and
      strength in estrogen dependent sarcopenia. 

PMID- 25578910
TI  - Proteomic analysis of isolated ciliary transition zones reveals the presence of
      ESCRT proteins.
AB  - The transition zone (TZ) is a specialized region of the cilium characterized by Y
      shaped connectors between the microtubules of the ciliary axoneme and the ciliary
      membrane [1]. Located near the base of the cilium, the TZ is in the prime
      location to act as a gate for proteins into and out of the ciliary compartment, a
      role supported by experimental evidence [2-6]. The importance of the TZ has been
      underscored by studies showing that mutations affecting proteins located in the
      TZ result in cilia-related diseases, or ciliopathies, presenting symptoms
      including renal cysts, retinal degeneration, and situs inversus [7-9]. Some TZ
      proteins have been identified and shown to interact with each other through
      coprecipitation studies in vertebrate cells [4, 10, 11] and genetics studies in
      C. elegans [3]. As a distinct approach to identify TZ proteins, we have taken
      advantage of the biology of Chlamydomonas to isolate TZs. Proteomic analysis
      identified 115 proteins, ten of which were known TZ proteins related to
      ciliopathies, indicating that the preparation was highly enriched for TZs.
      Interestingly, six proteins of the endosomal sorting complexes required for
      transport (ESCRT) were also associated with the TZs. Identification of these and
      other proteins in the TZ will provide new insights into functions of the TZ, as
      well as candidate ciliopathy genes.

PMID- 25578924
TI  - Pupil size dynamics during fixation impact the accuracy and precision of video
      based gaze estimation.
AB  - Video-based eye tracking relies on locating pupil center to measure gaze
      positions. Although widely used, the technique is known to generate spurious gaze
      position shifts up to several degrees in visual angle because pupil centration
      can change without eye movement during pupil constriction or dilation. Since
      pupil size can fluctuate markedly from moment to moment, reflecting arousal state
      and cognitive processing during human behavioral and neuroimaging experiments,
      the pupil size artifact is prevalent and thus weakens the quality of the video
      based eye tracking measurements reliant on small fixational eye movements.
      Moreover, the artifact may lead to erroneous conclusions if the spurious signal
      is taken as an actual eye movement. Here, we measured pupil size and gaze
      position from 23 human observers performing a fixation task and examined the
      relationship between these two measures. Results disclosed that the pupils
      contracted as fixation was prolonged, at both small (<16s) and large (~4min) time
      scales, and these pupil contractions were accompanied by systematic errors in
      gaze position estimation, in both the ellipse and the centroid methods of pupil
      tracking. When pupil size was regressed out, the accuracy and reliability of gaze
      position measurements were substantially improved, enabling differentiation of
      0.1 degrees  difference in eye position. We confirmed the presence of systematic
      changes in pupil size, again at both small and large scales, and its tight
      relationship with gaze position estimates when observers were engaged in a
      demanding visual discrimination task. 

PMID- 25578925
TI  - The effectiveness of two community-based weight loss strategies among obese, low
      income US Latinos.
AB  - BACKGROUND: Latino immigrants have high rates of obesity and face barriers to
      weight loss. OBJECTIVE: To evaluate the effectiveness of a case-management (CM)
      intervention with and without community health workers (CHWs) for weight loss.
      DESIGN: This was a 2-year, randomized controlled trial comparing two
      interventions with each other and with usual care (UC). PARTICIPANTS/SETTING:
      Eligible participants included Latinos with a body mass index of 30 to 60 and one
      or more heart disease risk factors. The 207 participants recruited during 2009
      2010 had a mean age of 47 years and were mostly women (77%). At 24 months, 86% of
      the sample was assessed. INTERVENTION: The CM+CHW (n=82) and CM (n=84)
      interventions were compared with each other and with UC (n=41). Both included an
      intensive 12-month phase followed by 12 months of maintenance. The CM+CHW group
      received home visits. MAIN OUTCOME MEASURES: Weight change at 24 months.
      STATISTICAL ANALYSES: Generalized estimating equations using intent-to-treat.
      RESULTS: At 6 months, mean weight loss in the CM+CHW arm was -2.1 kg (95% CI -2.8
      to -1.3) or -2% of baseline weight (95% CI -1% to -2%) compared with -1.6 kg (95%
      CI -2.4 to -0.7; % weight change, -2%, -1%, and -3%) in CM and -0.9 kg (95% CI 
      1.8 to 0.1; % weight change, -1%, 0%, and -2%) in UC. By 12 and 24 months,
      differences narrowed and CM+CHW was no longer statistically distinct. Men
      achieved greater weight loss than women in all groups at each time point
      (P<0.05). At 6 months, men in the CM+CHW arm lost more weight (-4.4 kg; 95% CI 
      6.0 to -2.7) compared with UC (-0.4 kg; 95% CI -2.4 to 1.5), but by 12 and 24
      months differences were not significant. CONCLUSIONS: This study demonstrated
      that incorporation of CHWs may help promote initial weight loss, especially among
      men, but not weight maintenance. Additional strategies to address social and
      environmental influences may be needed for Latino immigrant populations.

PMID- 25578926
TI  - !Cocinar Para Su Salud!: Randomized Controlled Trial of a Culturally Based
      Dietary Intervention among Hispanic Breast Cancer Survivors.
AB  - BACKGROUND: There is a need for culturally relevant nutrition programs targeted
      to underserved cancer survivors. OBJECTIVE: Our aim was to examine the effect of
      a culturally based approach to dietary change on increasing fruit/vegetable (F/V)
      intake and decreasing fat intake among Hispanic breast cancer survivors. DESIGN:
      Participants were randomized to Intervention and Control groups. Diet recalls,
      detailed interviews, fasting blood, and anthropometric measures were collected at
      baseline, 3, 6, and 12 months. PARTICIPANTS/SETTING: Hispanic women (n=70) with
      stage 0 to III breast cancer who completed adjuvant treatment and lived in New
      York City were randomized between April 2011 and March 2012. INTERVENTION: The
      Intervention group (n=34) participated in !Cocinar Para Su Salud!, a culturally
      based nine-session (24 hours over 12 weeks) intervention including nutrition
      education, cooking classes, and food-shopping field trips. The Control group
      (n=36) received written dietary recommendations for breast cancer survivors. MAIN
      OUTCOME MEASURES: Change at 6 months in daily F/V servings and percent calories
      from total fat were the main outcome measures. STATISTICAL ANALYSES: Linear
      regression models adjusted for stratification factors and estimated marginal
      means were used to compare changes in diet from baseline to 3 and 6 months.
      RESULTS: Baseline characteristics were the following: mean age 56.6 years
      (standard deviation 9.7 years), mean time since diagnosis 3.4 years (standard
      deviation 2.7 years), mean body mass index (calculated as kg/m2) 30.9 (standard
      deviation 6.0), 62.9% with annual household income <=$15,000, mean daily servings
      of all F/V was 5.3 (targeted F/V 3.7 servings excluding legumes/juices/starchy
      vegetables/fried foods), and 27.7% of daily calories from fat. More than 60% in
      the Intervention group attended seven or more of nine classes, with overall study
      retention of 87% retention at 6 months. At month 6, the Intervention group
      compared with Control group reported an increase in mean servings of F/V from
      baseline (all F/V: +2.0 vs -0.1; P=0.005; targeted F/V: +2.7 vs +0.5; P=0.002)
      and a nonsignificant decrease in percent calories from fat (-7.5% vs -4.4%;
      P=0.23) and weight (-2.5 kg vs +3.8 kg; P=0.22). CONCLUSIONS: !Cocinar Para Su
      Salud! was effective at increasing short-term F/V intake in a diverse population
      of Hispanic breast cancer survivors.

PMID- 25578927
TI  - Daily blueberry consumption improves blood pressure and arterial stiffness in
      postmenopausal women with pre- and stage 1-hypertension: a randomized, double
      blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Postmenopausal women have a high prevalence of hypertension and often
      develop arterial stiffness thereby increasing cardiovascular disease risk.
      Although antihypertensive drug therapies exist, increasing numbers of people
      prefer natural therapies. In vivo studies and a limited number of clinical
      studies have demonstrated the antihypertensive and vascular-protective effects of
      blueberries. OBJECTIVE: To examine the effects of daily blueberry consumption for
      8 weeks on blood pressure and arterial stiffness in postmenopausal women with pre
      and stage 1-hypertension. DESIGN: This was an 8-week, randomized, double-blind,
      placebo-controlled clinical trial. PARTICIPANTS/SETTING: Forty-eight
      postmenopausal women with pre- and stage 1-hypertension recruited from the
      greater Tallahassee, FL, area participated. INTERVENTION: Participants were
      randomly assigned to receive either 22 g freeze-dried blueberry powder or 22 g
      control powder. MAIN OUTCOME MEASURES: Resting brachial systolic and diastolic
      blood pressures were evaluated and arterial stiffness was assessed using carotid
      femoral pulse wave velocity and brachial-ankle pulse wave velocity. C-reactive
      protein, nitric oxide, and superoxide dismutase were measured at baseline, 4
      weeks, and 8 weeks. STATISTICAL ANALYSES PERFORMED: Statistical analysis was
      performed using a split plot model of repeated measures analysis of variance.
      RESULTS: After 8 weeks, systolic blood pressure and diastolic blood pressure
      (131+/-17 mm Hg [P<0.05] and 75+/-9 mm Hg [P<0.01], respectively) and brachial
      ankle pulse wave velocity (1,401+/-122 cm/second; P<0.01) were significantly
      lower than baseline levels (138+/-14 mm Hg, 80+/-7 mm Hg, and 1,498+/-179
      cm/second, respectively), with significant (P<0.05) group*time interactions in
      the blueberry powder group, whereas there were no changes in the group receiving
      the control powder. Nitric oxide levels were greater (15.35+/-11.16 MUmol/L;
      P<0.01) in the blueberry powder group at 8 weeks compared with baseline values
      (9.11+/-7.95 MUmol/L), whereas there were no changes in the control group.
      CONCLUSIONS: Daily blueberry consumption may reduce blood pressure and arterial
      stiffness, which may be due, in part, to increased nitric oxide production.

PMID- 25578928
TI  - Energy and Nutrient Intakes from Processed Foods Differ by Sex, Income Status,
      and Race/Ethnicity of US Adults.
AB  - BACKGROUND: The 2010 Dietary Guidelines for Americans (DGA) recommends nutrients
      to increase and to decrease for US adults. The contributions processed foods make
      to the US intake of nutrients to increase and decrease may vary by the level of
      processing and by population subgroup. OBJECTIVE: The hypotheses that the intakes
      of nutrients to increase or decrease, as specified by the DGA, are contributed
      exclusively from certain processed food categories and consumed differentially by
      population subgroups by sex, poverty-income ratio (ratio of household income to
      poverty threshold), and race/ethnicity was tested along with the hypothesis that
      specific processed food categories are responsible for nutrient intake
      differences between the population subgroups. DESIGN: The 24-hour dietary recall
      data from the cross-sectional 2003-2008 National Health and Nutrition Examination
      Survey was used to determine population subgroup energy and nutrient intake
      differences among processed food categories defined by the International Food
      Information Council Foundation Continuum of Processed Foods.
      PARTICIPANTS/SETTING: Fifteen thousand fifty-three US adults aged >=19 years.
      STATISTICAL ANALYSES PERFORMED: The mean daily intake of energy and nutrients
      from processed food categories reported by population subgroups were compared
      using regression analysis to determine covariate-adjusted least square means.
      RESULTS: Processed food categories that contributed to energy and nutrient intake
      differences within subgroups did not uniformly or exclusively contribute
      nutrients to increase or decrease per DGA recommendations. The between-group
      differences in mean daily intake of both nutrients to increase and decrease
      contributed by the various processed food categories were diverse and were not
      contributed exclusively from specific processed food categories. CONCLUSIONS:
      Recommendations for a diet adhering to the DGA should continue to focus on the
      energy and nutrient content, frequency of consumption, and serving size of
      individual foods rather than the level of processing.

PMID- 25578930
TI  - Risk of cardiovascular thrombotic events after surgical castration versus
      gonadotropin-releasing hormone agonists in Chinese men with prostate cancer.
AB  - We investigated the cardiovascular thrombotic risk after surgical castration (SC)
      versus gonadotropin-releasing hormone agonists (GnRHa) in Chinese men with
      prostate cancer. All Chinese prostate cancer patients who were treated with SC or
      GnRHa from year 2000 to 2009 were reviewed and compared. The primary outcome was
      any new-onset of cardiovascular thrombotic events after SC or GnRHa, which was
      defined as any event of acute myocardial infarction or ischemic stroke. The risk
      of new-onset cardiovascular thrombotic event was compared between the SC group
      and the GnRHa group using Kaplan-Meier method. Multivariate Cox regression
      analysis was performed to adjust for other potential confounding factors. A total
      of 684 Chinese patients was included in our study, including 387 patients in the
      SC group and 297 patients in the GnRHa group. The mean age in the SC group (75.3
      +/- 7.5 years) was significantly higher than the GnRHa group (71.8 +/- 8.3 years)
      (P < 0.001). There was increased risk of new cardiovascular thrombotic events in
      the SC group when compared to the GnRHa group upon Kaplan-Meier analysis (P =
      0.014). Upon multivariate Cox regression analysis, age (hazard ratio [HR] 1.072,
      95% confidence interval [CI] 1.04-1.11, P< 0.001), hyperlipidemia (HR 2.455, 95%
      CI 1.53-3.93, P< 0.001), and SC (HR 1.648, 95% CI 1.05-2.59, P= 0.031) were
      significant risk factors of cardiovascular thrombotic events. In conclusion, SC
      was associated with increased risk of cardiovascular thrombotic events when
      compared to GnRHa. This is an important aspect to consider while deciding on the
      method of androgen deprivation therapy, especially in elderly men with known
      history of hyperlipidemia. 

PMID- 25578931
TI  - Urokinase-type plasminogen activator: a new target for male contraception?
AB  - Urokinase-type plasminogen activator (uPA) is closely related to male
      reproduction. With the aim of investigating the possibility for uPA as a
      potential contraceptive target, in the present work, Kunming male mice were
      immunized by human uPA subcutaneous injection at three separate doses for 3
      times. Then the potency of the anti-human uPA antibody in serum was analyzed, and
      mouse fertility was evaluated. Serum antibody titers for human uPA in immunized
      groups all reached 1:10,240 or higher levels by enzyme linked immunosorbent
      assay, and mating experiments revealed that pregnancy rates and the mean number
      of embryos implanted after mating declined obviously (P < 0.05) when compared
      with control groups. However, the mating capacity and reproductive organ weights
      had no obvious change, and histological analysis of the testes and epididymides
      also showed normal morphology for immunized male mice. Sperm function tests
      suggested that the sperm concentration, sperm viability, sperm motility, and in
      vitro fertilization rate for the cauda epididymis sperm in uPA-immunized groups
      were lower than those in the controls (P < 0.05). Together, these observations
      indicated that subcutaneous injection human uPA to the male mice could
      effectively reduce their fertility, and uPA could become a new target for
      immunocontraception in male contraceptive development. 

PMID- 25578929
TI  - The role of sex chromosomes in mammalian germ cell differentiation: can the germ
      cells carrying X and Y chromosomes differentiate into fertile oocytes?
AB  - The sexual differentiation of germ cells into spermatozoa or oocytes is strictly
      regulated by their gonadal environment, testis or ovary, which is determined by
      the presence or absence of the Y chromosome, respectively. Hence, in normal
      mammalian development, male germ cells differentiate in the presence of X and Y
      chromosomes, and female germ cells do so in the presence of two X chromosomes.
      However, gonadal sex reversal occurs in humans as well as in other mammalian
      species, and the resultant XX males and XY females can lead healthy lives, except
      for a complete or partial loss of fertility. Germ cells carrying an abnormal set
      of sex chromosomes are efficiently eliminated by multilayered surveillance
      mechanisms in the testis, and also, though more variably, in the ovary. Studying
      the molecular basis for sex-specific responses to a set of sex chromosomes during
      gametogenesis will promote our understanding of meiotic processes contributing to
      the evolution of sex determining mechanisms. This review discusses the fate of
      germ cells carrying various sex chromosomal compositions in mouse models, the
      limitation of which may be overcome by recent successes in the differentiation of
      functional germ cells from embryonic stem cells under experimental conditions. 

PMID- 25578932
TI  - Alternatives to testosterone replacement: testosterone restoration.
AB  - The European Male Aging Study has demonstrated that the hypogonadism of male
      aging is predominantly secondary. Theoretically with appropriate stimulation from
      the pituitary, the aging testis should be able to produce eugonadal levels of
      testosterone. The strategies for the treatment of late onset hypogonadism (LOH)
      have focused on replacement with exogenous testosterone versus restoration of
      endogenous production. The purpose of this article is to review existing peer
      reviewed literature supporting the concept of restoration of endogenous
      testosterone in the treatment of LOH. 

PMID- 25578933
TI  - Personalized prostate cancer therapy based on systems analysis of the apoptosis
      regulatory network.
AB  - Targeting the androgen receptor axis provides only temporary relief for advanced
      prostate cancer, which often evolves into androgen-independent disease. The wide
      variety of signaling mechanisms connected with the pathophysiology of androgen
      independent prostate cancer poses both conceptual and practical challenges for
      the design of efficient therapies. Analysis of apoptosis regulation in prostate
      cancer suggests the potential value of a systems approach that integrates
      information on the topology of the antiapoptotic signaling network, the signal
      transduction pathways that inhibit apoptosis, and the expression of proteins of
      the Bcl2 family. This approach could be used to identify patients most likely to
      respond to treatments with drugs that inhibit the signaling pathways controlling
      apoptosis. 

PMID- 25578934
TI  - Upgrading and upstaging of low-risk prostate cancer among Korean patients: a
      multicenter study.
AB  - Only 54% of prostate cancer cases in Korea are localized compared with 82% of
      cases in the US. Furthermore, half of Korean patients are upgraded after radical
      prostatectomy (41.6%-50.6%). We investigated the risk factors for upgrading
      and/or upstaging of low-risk prostate cancer after radical prostatectomy. We
      retrospectively reviewed the medical records of 1159 patients who underwent
      radical prostatectomy at five hospitals in Honam Province. Preoperative data on
      standard clinicopathological parameters were collected. The radical prostatectomy
      specimens were graded and staged and we defined a "worsening prognosis" as a
      Gleason score >= 7 or upstaging to >= pT3. Multivariate logistic regression
      models were used to assess factors associated with postoperative pathological
      upstaging. Among the 1159 patients, 324 were classified into the clinically low
      risk group, and 154 (47.5%) patients were either upgraded or upstaged. The
      multivariable analysis revealed that the preoperative serum prostate-specific
      antigen level (odds ratio [OR], 1.131; 95% confidence interval [CI], 1.007-1.271;
      P= 0.037), percent positive biopsy core (OR: 1.018; 95% CI: 1.002-1.035; P=
      0.032), and small prostate volume (<=30 ml) (OR: 2.280; 95% CI: 1.351-3.848; P=
      0.002) were predictive of a worsening prognosis. Overall, 47.5% of patients with
      low-risk disease were upstaged postoperatively. The current risk stratification
      criteria may be too relaxed for our study cohort. 

PMID- 25578936
TI  - Modified technique in treating recurrent priapism: a technique report.
AB  - Recurrent ischemic priapism is a problem in clinical treatment. Most of the cases
      require more invasive surgery to shunt the blood stasis. We introduce a modified
      technique in treating recurrent ischemic priapism. The technique described is
      applied to acute ischaemic priapic episodes in patients with a history of
      stuttering priapism. It was carried out by a Winter's shunt combined with a
      continuous cavernosal irrigation system. Priapism was effectively resolved on the
      patients without recurrence. The four patients who received this treatment
      recovered most sexual function after 6 months follow-up. 

PMID- 25578935
TI  - Prostate-specific antigen-based population screening for prostate cancer: current
      status in Japan and future perspective in Asia.
AB  - In Western countries, clinical trials on prostate cancer screening demonstrated a
      limited benefit for patient survival. In the Asia-Pacific region, including
      Japan, the rate of prostate-specific antigen (PSA) testing remains very low
      compared with Western countries, and the benefits of population-based screening
      remain unclear. This review describes the current status of population screening
      and diagnosis for prostate cancer in Japan and discusses the efficacy of
      population screening for the Asian population. Since the 1990s, screening systems
      have been administered by each municipal government in Japan, and decreases in
      the prostate cancer mortality rate are expected in some regions where the
      exposure rate to PSA screening has increased markedly. A population-based
      screening cohort revealed that the proportion of metastatic disease in cancer
      detected by screening gradually decreased according to the increased exposure
      rate, and a decreasing trend in the proportion of cancer with high serum PSA
      levels after population screening was started. The prognosis of the prostate
      cancer detected by population screening was demonstrated to be more favorable
      than those diagnosed outside of the population screening. Recent results in
      screening cohorts demonstrated the efficacy of PSA. These recent evidences
      regarding population-based screening in Japan may contribute to establishing the
      optimal prostate cancer screening system in Asian individuals. 

PMID- 25578937
TI  - The secretory products of Trichomonas vaginalis decrease fertilizing capacity of
      mice sperm in vitro.
AB  - Trichomonas vaginalis infection is one of the most prevalent sexually transmitted
      infections in humans and is now recognized as an important cause of infertility
      in men. There is little information about the effect of extracellular polymeric
      substances (EPS) from T. vaginalis on sperm, but previous reports do not provide
      a conclusive description of the functional integrity of the sperm. To investigate
      the impact of EPS on the fertilizing capacity of sperm, we assessed sperm
      motility, acrosomal status, hypo-osmotic swelling, and in vitrofertilization rate
      after incubating the sperm with EPS in vitrousing mice. The incubation of sperm
      with EPS significantly decreased sperm motility, viability, and functional
      integrity in a concentration and time-dependent manner. These effects on sperm
      quality also resulted in a decreased fertilization rate in vitro. This is the
      first report that demonstrates the direct negative impact of the EPS of T.
      vaginalis on the fertilization rate of sperm in vitro. However, further study
      should be performed using human sperm to determine if EPS has similar negative
      impact on human sperm fertilizing capacity in vitro. 

PMID- 25578939
TI  - Exploring the epididymis: a personal perspective on careers in science.
AB  - Science is a profession of inquiry. We ask ourselves what is it we see and why
      our observations happen the way they do. Answering those two question puts us in
      the company of those early explorers, who from Europe found the New World, and
      from Asia reached west to encounter Europe. Vasco Nunez de Balboa of Spain was
      such an explorer. He was the first European to see or "discover" the Pacific
      Ocean. One can imagine his amazement, his excitement when he first saw from a
      mountain top that vast ocean previously unknown to his culture. A career in
      science sends each of us seeking our own "Balboa Moments," those observations or
      results that surprise or even amaze us, those discoveries that open our eyes to
      new views of nature and medicine. Scientists aim to do what those early explorers
      did: discover what has previously been unknown, see what has previously been
      unseen, and reveal what has previously been hidden. Science requires the
      scientist to discover the facts from among many fictions and to separate the
      important facts from the trivial so that knowledge can be properly developed. It
      is only with knowledge that old dogmas can be challenged and corrected. Careers
      in science produce specific sets of knowledge. When pooled with other knowledge
      sets they eventually contribute to wisdom and it is wisdom, we hope, that will
      improve the human condition. 

PMID- 25578938
TI  - Reversal of idiopathic hypogonadotropic hypogonadism: a cohort study in Chinese
      patients.
AB  - Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been
      viewed as a life-long disease caused by a deficiency of gonadotropin-releasing
      hormone neurons, a portion of patients may gradually regain normal reproductive
      axis function during hormonal replacement therapy. The predictive factors for
      potential IHH reversal are largely unknown. The aim of our study was to
      investigate the incidence and clinical features of IHH male patients who had
      reversed reproductive axis function. In this retrospective cohort study, male IHH
      patients were classified into a reversal group (n = 18) and a nonreversal group
      (n = 336). Concentration of gonadotropins and testosterone, as well as testicle
      sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired
      normal reproductive function during treatment. The median age for reversal was 24
      years old (range 21-34 years). Compared with the nonreversal group, the
      reversible group had higher basal luteinizing hormone (LH) (1.0 +/- 0.7 IU l -[1]
      vs 0.4 +/- 0.4 IU l-1 , P< 0.05) and stimulated LH (28.3 +/- 22.6 IU l-1 vs 1.9
      +/- 1.1 IU l-1 , P< 0.01) levels, as well as larger testicle size (5.1 +/- 2.6 ml
      vs 1.5 +/- 0.3 ml, P< 0.01), at the initial visit. In summary, larger testicle
      size and higher stimulated LH concentrations are favorite parameters for
      reversal. Our finding suggests that reversible patients may retain partially
      active reproductive axis function at initial diagnosis. 

PMID- 25578940
TI  - Commentary on "validation of robot-assisted vasectomy reversal" by Dr. Parviz K
      Kavoussi.

PMID- 25578941
TI  - Commentary on "validation of robot-assisted vasectomy reversal".

PMID- 25578943
TI  - Towards understanding the design of dual-modal MR/fluorescent probes to sense
      zinc ions.
AB  - A series of gadolinium complexes were synthesised in order to test the design of
      dual-modal probes that display a change in fluorescence or relaxivity response
      upon binding of zinc. A dansyl-DO3ATA gadolinium complex [GdL1] displayed an
      increase and a slight blue-shift in fluorescence in the presence of zinc;
      however, a decrease in relaxation rate was observed. Consequently, the ability of
      the well-known zinc chelator, BPEN, was assessed for relaxivity response when
      conjugated to the gadolinium chelate. The success of this probe [GdL2], lead to
      the inclusion of the same zinc-probing moiety alongside a longer wavelength
      emitting fluorophore, rhodamine [GdL3], to arrive at the final iteration of these
      first generation dual-modal zinc-sensing probes. The compounds give insight into
      the design protocols required for the successful imaging of zinc ions.

PMID- 25578942
TI  - 3D-printed microfluidic device for the detection of pathogenic bacteria using
      size-based separation in helical channel with trapezoid cross-section.
AB  - A facile method has been developed to detect pathogenic bacteria using magnetic
      nanoparticle clusters (MNCs) and a 3D-printed helical microchannel. Antibody
      functionalized MNCs were used to capture E. coli (EC) bacteria in milk, and the
      free MNCs and MNC-EC complexes were separated from the milk using a permanent
      magnet. The free MNCs and MNC-EC complexes were dispersed in a buffer solution,
      then the solution was injected into a helical microchannel device with or without
      a sheath flow. The MNC-EC complexes were separated from the free MNCs via the
      Dean drag force and lift force, and the separation was facilitated in the
      presence of a sheath flow. The concentration of the E. coli bacteria was
      determined using a light absorption spectrometer, and the limit of detection was
      found to be 10 cfu/mL in buffer solution and 100 cfu/mL in milk. 

PMID- 25578945
TI  - Acute effects of flexible pole exercise on heart rate dynamics.
AB  - INTRODUCTION: Exercise with flexible poles provides fast eccentric and concentric
      muscle contractions. Although the literature reports significant muscle chain
      activity during this exercise, it is not clear if a single bout of exercise
      induces cardiac changes. In this study we assessed the acute effects of flexible
      pole exercise on cardiac autonomic regulation. METHODS: The study was performed
      on 22 women between 18 and 26 years old. We assessed heart rate variability (HRV)
      in the time (SDNN, RMSSD and pNN50) and frequency (HF, LF and LF/HF ratio)
      domains and geometric indices of HRV (RRTri, TINN, SD1, SD2 and SD1/SD2 ratio).
      The subjects remained at rest for 10 min and then performed the exercises with
      the flexible poles. Immediately after the exercise protocol, the volunteers
      remained seated at rest for 60 min and HRV was analyzed. RESULTS: We observed no
      significant changes in time domain (SDNN: p=0.72; RMSSD: p=0.94 and pNN50:
      p=0.92) or frequency domain indices (LF [nu]: p=0.98; LF [ms(2)]: p=0.72; HF
      [nu]: p=0.98; HF [ms(2)]: p=0.82 and LF/HF ratio: p=0.7) or in geometric indices
      (RRTri: p=0.54; TINN: p=0.77; SD1: p=0.94; SD2: p=0.67 and SD/SD2: p=0.42) before
      and after a single bout of flexible pole exercise. CONCLUSION: A single bout of
      flexible pole exercise did not induce significant changes in cardiac autonomic
      regulation in healthy women.

PMID- 25578946
TI  - Influence of gender on prognosis of acute coronary syndromes.
AB  - INTRODUCTION: Ischemic heart disease presents different features in men and
      women. We analyzed the relation between gender and prognosis in patients who had
      suffered a high-risk acute coronary syndrome (ACS). METHODS: This was a
      prospective analytical cohort study performed at Lozano Blesa University
      Hospital, Zaragoza, Spain, of 559 patients diagnosed with high-risk ACS with and
      without ST-segment elevation according to the American College of
      Cardiology/American Heart Association guidelines. The sample was divided into two
      groups by gender and differences in epidemiologic, laboratory,
      electrocardiographic and echocardiographic variables and treatment were recorded.
      A Cox's proportional hazard model was applied and 6-month mortality was analyzed
      as the main variable. RESULTS: The median age was 65.2+/-12.7 years, and 21.8%
      were women. Baseline characteristics in women were more unfavorable, with higher
      GRACE scores, older age, higher prevalence of hypertension, diabetes and heart
      failure, lower ejection fraction and more renal dysfunction at admission. Women
      suffered more adverse cardiovascular events (27.9% vs. 15.8%, p=0.002). Sixty
      four patients died, 18.9% of the women vs. 9.4% of the men (p=0.004). After
      multivariate analysis, female gender did not present an independent relation with
      mortality. Hemoglobin level, renal function, ejection fraction and Killip class
      >1 presented significant differences. CONCLUSIONS: Acute syndrome coronary in
      women has a worse prognosis than in men. Their adverse course is due to their
      baseline characteristics and not to their gender.

PMID- 25578944
TI  - Second-generation antipsychotics and neuroleptic malignant syndrome: systematic
      review and case report analysis.
AB  - BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare, severe, idiosyncratic
      adverse reaction to antipsychotics. Second-generation antipsychotics (SGAs) were
      originally assumed to be free from the risk of causing NMS, however several cases
      of NMS induced by SGAs (SGA-NMS) have been reported. OBJECTIVES: The aim of this
      study was to systematically review available studies and case reports on SGA-NMS
      and compare the presentation of NMS induced by different SGAs. DATA SOURCES:
      Citations were retrieved from PubMed up to November 2013, and from reference
      lists of relevant citations. STUDY ELIGIBILITY CRITERIA: Eligibility criteria
      included (a) primary studies reporting data on NMS, with at least 50 % of the
      sample receiving SGAs; or (b) case reports and case reviews reporting on NMS
      induced by SGA monotherapy, excluding those due to antipsychotic withdrawal.
      STUDY APPRAISAL AND SYNTHESIS METHODS: A standardized method for data extraction
      and coding was developed for the analysis of eligible case reports. RESULTS: Six
      primary studies and 186 individual cases of NMS induced by SGAs were included.
      Primary studies suggest that SGA-NMS is characterized by lower incidence, lower
      clinical severity, and less frequent lethal outcome than NMS induced by first
      generation antipsychotics. Systematic analysis of case reports suggests that even
      the most recently marketed antipsychotics are not free from the risk of inducing
      NMS. Furthermore, clozapine-, aripiprazole- and amisulpride-induced NMS can
      present with atypical features more frequently than other SGA-NMS, i.e.
      displaying less intense extrapyramidal symptoms or high fever. LIMITATIONS: Case
      reports report non-systematic data, therefore analyses may be subject to bias.
      CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Clinicians should be aware that NMS
      is virtually associated with all antipsychotics, including those most recently
      marketed. Although apparently less severe than NMS induced by older
      antipsychotics, SGA-NMS still represent a relevant clinical issue.

PMID- 25578947
TI  - [Erratum to "Medication adverse events: Impact of pharmaceutical consultations
      during the hospitalization of patients" [Ann. Pharm. Fr. 72 (2014) 440-450].]

PMID- 25578948
TI  - Protease-activated receptor-2 inhibits BK channel activity in bronchopulmonary
      sensory neurons.
AB  - Activation of protease-activated receptor-2 (PAR2) contributes to airway
      inflammation and airway hypersensitivity, the hallmark features of allergic
      asthma; and a neurogenic mechanism involving hypersensitivity of bronchopulmonary
      sensory nerves has been indicated. Large-conductance Ca(2+)-activated potassium
      (BK) channels are known to play an important role in shaping neuronal
      excitability. The aim of this study was to investigate the potential regulation
      of BK channel activities by PAR2 activation in vagal bronchopulmonary sensory
      neurons. Our results showed that pretreatment with PAR2-activating peptide (PAR2
      AP; 100MUM, 120s), but not its control peptide PAR2-RP, significantly reduced BK
      current density in these neurons. Inhibition of phospholipase C, PKC, PKA or
      MEK/ERK signaling pathway did not prevent the suppression of BK current by PAR2
      activation; whereas intracellular application of Ca(2+) chelator BAPTA-AM
      completely abolished the PAR2 regulation of BK current. In addition, our results
      demonstrated that activation of PAR2 increased excitability of bronchopulmonary
      sensory neurons, in a similar manner as displayed by a direct BK channel
      blockade. In summary, our data suggest that suppression of BK channel activity
      contributes to PAR2 activation-induced hyperexcitability of vagal
      bronchopulmonary sensory neurons. 

PMID- 25578950
TI  - Asymmetrical intersection between the middle cerebral artery and rhinal vein
      suggests asymmetrical gustatory cortex location in rodent hemispheres.
AB  - The rodent gustatory cortex is located in the anterior part of the insular
      cortex, which is near the dorsal part of the rhinal vein (RHV) and the
      intersection of the anterior and posterior regions of the middle cerebral artery
      (MCA). Thus, the intersection between the RHV and MCA is used as a landmark for
      the rodent gustatory cortex. In our previous study, we employed functional
      magnetic resonance imaging (MRI) to demonstrate that tastants evoked bilateral
      responses in the rodent insular cortices, but that these representations were
      asymmetrical between the hemispheres. In the present study, to clarify the
      observed asymmetrical responses, we performed magnetic resonance angiography in a
      7.0-Tesla MRI scanner to determine the anatomical position of the rodent
      gustatory cortex, which was identified using the intersection of the MCA and RHV.
      We successfully observed the intersection while administering carbogen as an
      inhaled gas and found that the intersection in the left hemisphere is more
      anterior compared to that in the right hemisphere. Taken together with the
      previous functional MRI results, this result indicates that the gustatory
      representation in relation to the intersection may be identically conserved in
      the insular cortex of both hemispheres; therefore, the rodent gustatory cortex
      may be asymmetrically located between the left and right hemispheres. The result
      also suggests that this landmark location needs to be verified when investigating
      gustatory representations and responses. 

PMID- 25578951
TI  - The electroretinogram of Mongolian gerbil (Meriones unguiculatus): comparison to
      mouse.
AB  - The Mongolian gerbil (Meriones unguiculatus) is a diurnal rodent whose retinal
      photoreceptors comprise 13% cones in contrast to 1-3% in nocturnal mice and rats.
      Moreover, it displays a retinal structure more analogous to that of human than of
      mouse. However, the electroretinogram (ERG) recordings of gerbils have not yet
      been well studied. Thus, here we compared the ERGs of gerbils and C57 mice. We
      recorded responses to full-field flashes of increasing intensities under both
      dark and light adaptation. We also investigated responses to flickers of
      increasing frequencies and to long-duration flashes under photopic conditions. In
      scotopic, the amplitudes of the gerbil a- and b-waves are slightly smaller than
      those of the mouse waves. However, in photopic, the gerbil wave amplitudes are 2
      fold larger than those of mice. Gerbils also exhibit larger flicker responses and
      higher flicker fusion frequencies than mice. Furthermore, unlike mice, gerbils
      show a positive OFF response (d-wave) and a post b-wave positive potential (i
      wave), features commonly observed in human photopic ERGs. Our results suggest
      that gerbils may complement rod-dominant mice as models for studying retinal cone
      function and pathologies. 

PMID- 25578952
TI  - Deep brain stimulation of the nucleus accumbens shell induces anti-obesity
      effects in obese rats with alteration of dopamine neurotransmission.
AB  - The aim of this study was to assess the anti-obesity effects of nucleus accumbens
      shell (NAc-sh) deep brain stimulation (DBS) in diet-induced obese (DIO) and chow
      fed (chow) rats. The influence of DBS on dopamine (DA) signaling in the NAc-sh
      was also evaluated. DIO and chow rats were subjected to DBS for 14 consecutive
      days. Food intake and weight gain were measured daily. The gene expression of the
      dopamine D1 and D2 receptors was evaluated by qPCR. In addition, the
      extracellular levels of DA and its metabolite, dihydroxyphenylacetic acid
      (DOPAC), were determined by microdialysis. We observed that chronic DBS induced
      significant reductions in total energy intake (596.0+/-65.0kcal vs. 1161.6+/
      22.2kcal, p<0.001) and weight gain (1.45+/-0.57% vs. 9.64+/-0.38%, p<0.001) in
      DIO rats compared to sham-DIO rats. Up-regulated D2 receptor gene expression
      (2.43+/-0.12 vs. 0.64+/-0.04, p<0.001) and increased DA levels (2.73+/
      0.15pmol/mL vs. 0.62+/-0.05pmol/mL, p<0.001) were observed in DIO rats compared
      to sham-DIO rats. DBS had no influence on food intake, weight gain, or DA
      neurotransmission in chow rats. Our results support an association of the
      anorexigenic effects of NAc-sh DBS with mesolimbic DA signaling and indicate that
      the positive alteration of DA function in DIO rats may be responsible for the
      different effects of DBS in DIO and chow rats. 

PMID- 25578954
TI  - Direct construction of 2-alkylbenzo-1,3-azoles via C-H activation of alkanes for
      C-C and C-X (X = O, S) bond formation.
AB  - Copper catalyzed straightforward synthesis of 2-alkylbenzoxa(thia)azoles from
      aryl isocyanates/isothiocyanates and simple alkanes is reported. The protocol
      utilizes ditertiary butyl peroxide (DTBP) as a radical initiator and involves
      sequential formation of C-C and C-X (X = O, S) bonds followed by aromatization in
      a one-pot procedure. 

PMID- 25578949
TI  - Dendritic spine dysgenesis in autism related disorders.
AB  - The activity-dependent structural and functional plasticity of dendritic spines
      has led to the long-standing belief that these neuronal compartments are the
      subcellular sites of learning and memory. Of relevance to human health, central
      neurons in several neuropsychiatric illnesses, including autism related
      disorders, have atypical numbers and morphologies of dendritic spines. These so
      called dendritic spine dysgeneses found in individuals with autism related
      disorders are consistently replicated in experimental mouse models. Dendritic
      spine dysgenesis reflects the underlying synaptopathology that drives clinically
      relevant behavioral deficits in experimental mouse models, providing a platform
      for testing new therapeutic approaches. By examining molecular signaling
      pathways, synaptic deficits, and spine dysgenesis in experimental mouse models of
      autism related disorders we find strong evidence for mTOR to be a critical point
      of convergence and promising therapeutic target. 

PMID- 25578953
TI  - Functional MRI and CT biomarkers in oncology.
AB  - Imaging biomarkers derived from MRI or CT describe functional properties of
      tumours and normal tissues. They are finding increasing numbers of applications
      in diagnosis, monitoring of response to treatment and assessment of progression
      or recurrence. Imaging biomarkers also provide scope for assessment of
      heterogeneity within and between lesions. A wide variety of functional parameters
      have been investigated for use as biomarkers in oncology. Some imaging techniques
      are used routinely in clinical applications while others are currently restricted
      to clinical trials or preclinical studies. Apparent diffusion coefficient,
      magnetization transfer ratio and native T1 relaxation time provide information
      about structure and organization of tissues. Vascular properties may be described
      using parameters derived from dynamic contrast-enhanced MRI, dynamic contrast
      enhanced CT, transverse relaxation rate (R2*), vessel size index and relative
      blood volume, while magnetic resonance spectroscopy may be used to probe the
      metabolic profile of tumours. This review describes the mechanisms of contrast
      underpinning each technique and the technical requirements for robust and
      reproducible imaging. The current status of each biomarker is described in terms
      of its validation, qualification and clinical applications, followed by a
      discussion of the current limitations and future perspectives. 

PMID- 25578956
TI  - Symbiosis: Sweet talking your partner.

PMID- 25578958
TI  - On changing neckties: a few remarks on the art of teaching.

PMID- 25578955
TI  - The BER necessities: the repair of DNA damage in human-adapted bacterial
      pathogens.
AB  - During colonization and disease, bacterial pathogens must survive the onslaught
      of the host immune system. A key component of the innate immune response is the
      generation of reactive oxygen and nitrogen species by phagocytic cells, which
      target and disrupt pathogen molecules, particularly DNA, and the base excision
      repair (BER) pathway is the most important mechanism for the repair of such
      oxidative DNA damage. In this Review, we discuss how the human-specific pathogens
      Mycobacterium tuberculosis, Helicobacter pylori and Neisseria meningitidis have
      evolved specialized mechanisms of DNA repair, particularly their BER pathways,
      compared with model organisms such as Escherichia coli. This specialization in
      DNA repair is likely to reflect the distinct niches occupied by these important
      human pathogens in the host. 

PMID- 25578959
TI  - Pressure-induced phase transition of BiOF: novel two-dimensional layered
      structures.
AB  - Bismuth oxide haloids BiOXs (X = Cl, Br, I) have received attention as
      photocatalytic materials after TiO2 in recent years due to their unique layered
      structures. Using an ab initio evolutionary methodology structure search method,
      we systematically investigate the evolution of BiOF structures under pressure. It
      is found that BiOF can maintain its layered structure up to 300 GPa. Three stable
      new phases with Pnma, P3m1 and Cmcm structure at a pressure of 10, 66, and 286
      GPa have been identified for the first time. All the newly found phases are two
      dimensional layered structures characterized by Bi-O slabs interleaved with F(-)
      anion slabs. Moreover, all three phases are indirect semiconductors with wide
      band gaps. It is found that pressure can cause great change in the band gaps of
      BiOF. The band gaps of the high-pressure phases of BiOF vary nearly linearly with
      pressure but exhibit different pressure trends. The electronic structure,
      structural stability, phase transition mechanisms and evolution of the Bi-O slabs
      of BiOF under pressure are discussed.

PMID- 25578960
TI  - Detection of Botulinum Toxins A, B, E, and F in Foods by Endopep-MS.
AB  - Botulism is caused by exposure to botulinum neurotoxins (BoNTs). BoNTs are
      proteins secreted by some species of clostridia; these neurotoxins are known to
      interfere with nerve impulse transmission, thus causing paralysis. Botulism may
      be contracted through consumption of food either naturally or intentionally
      contaminated with BoNT. The human lethal dose of BoNT is not known but is
      estimated to be between 0.1 and 70 MUg; thus, it is important to be able to
      detect small amounts of this toxin in foods to ensure food safety and to identify
      the source of an outbreak. Our laboratory previously reported on the development
      of Endopep-MS, a mass-spectrometric-based endopeptidase method for the detection
      and differentiation of BoNT. This method can detect BoNT at levels below the
      historic standard mouse bioassay in clinical samples such as serum, stool, and
      culture supernatants. We have now expanded this assay to detect BoNT in over 50
      foods including representative products that were involved in actual botulism
      investigations. The foods tested by the Endopep-MS included those with various
      acidities, viscosities, and fat levels. Dairy and culturally diverse products
      were also included. This work demonstrates that the Endopep-MS method can be used
      to detect BoNT/A, /B, /E, and /F in foods at levels spiked below that of the
      limit of detection of the mouse bioassay. Furthermore, we successfully applied
      this method to investigate several foods associated with botulism outbreaks.

PMID- 25578957
TI  - Bacterial morphogenesis and the enigmatic MreB helix.
AB  - Work over the past decade has highlighted the pivotal role of the actin-like MreB
      family of proteins in the determination and maintenance of rod cell shape in
      bacteria. Early images of MreB localization revealed long helical filaments,
      which were suggestive of a direct role in governing cell wall architecture.
      However, several more recent, higher-resolution studies have questioned the
      existence or importance of the helical structures. In this Opinion article, I
      navigate a path through these conflicting reports, revive the helix model and
      summarize the key questions that remain to be answered.

PMID- 25578961
TI  - Use of lumbar laminoplasty vs. laminotomy for transection of the filum terminale
      does not affect early complication rates or postoperative course.
AB  - INTRODUCTION: Various techniques are used for spinal cord untethering. The
      purpose of this study was to compare patient characteristics, postoperative
      course, and early complications after laminotomy vs. laminoplasty for transection
      of the filum terminale for tethered cord release. METHODS: Retrospective analysis
      of clinical and magnetic resonance imaging data was undertaken for all patients
      (<18 years) who underwent tethered cord release by transection of the filum
      terminale at Oregon Health & Science University, Doernbecher Children's Hospital,
      from 2000 to 2011. RESULTS: Data from two hundred and forty-eight patients were
      analyzed. Mean age was 5.2 years (range 0.3 to 16.8 years). Access to the thecal
      space during surgery was achieved using laminotomy or laminoplasty in 82 (33.1 %)
      and 166 (66.9 %) patients, respectively. Laminoplasty patients were significantly
      younger than laminotomy patients (3.2 vs. 9.3 years, p<0.0001); other clinical
      and radiographic characteristics were similar between the groups. Nine patients
      (3.6 %) experienced early complications, including cerebrospinal fluid leak
      (n=2), suprafascial infection requiring surgical management and intravenous (IV)
      antibiotics (n=3) or IV antibiotics alone (n=1), a small area of peri-incisional
      cutaneous necrosis (n=1), perioperative seizures (n=1), and mild, transient
      malignant hyperthermia (n=1). There was no difference in the number of early
      complications between the two groups. Univariate and multivariate analyses
      revealed no significant risk factor for postoperative complication associated
      with technique. As judged by caregivers, independent of surgical technique, 97 %
      of patients improved after surgery. CONCLUSION: There was no difference in
      complication risk when performing transection of the filum terminale for tethered
      cord release using laminotomy or laminoplasty.

PMID- 25578962
TI  - Detection of recurrent alternative splicing switches in tumor samples reveals
      novel signatures of cancer.
AB  - The determination of the alternative splicing isoforms expressed in cancer is
      fundamental for the development of tumor-specific molecular targets for prognosis
      and therapy, but it is hindered by the heterogeneity of tumors and the
      variability across patients. We developed a new computational method, robust to
      biological and technical variability, which identifies significant transcript
      isoform changes across multiple samples. We applied this method to more than 4000
      samples from the The Cancer Genome Atlas project to obtain novel splicing
      signatures that are predictive for nine different cancer types, and find a
      specific signature for basal-like breast tumors involving the tumor-driver
      CTNND1. Additionally, our method identifies 244 isoform switches, for which the
      change occurs in the most abundant transcript. Some of these switches occur in
      known tumor drivers, including PPARG, CCND3, RALGDS, MITF, PRDM1, ABI1 and MYH11,
      for which the switch implies a change in the protein product. Moreover, some of
      the switches cannot be described with simple splicing events. Surprisingly,
      isoform switches are independent of somatic mutations, except for the tumor
      suppressor FBLN2 and the oncogene MYH11. Our method reveals novel signatures of
      cancer in terms of transcript isoforms specifically expressed in tumors,
      providing novel potential molecular targets for prognosis and therapy. Data and
      software are available at: http://dx.doi.org/10.6084/m9.figshare.1061917 and
      https://bitbucket.org/regulatorygenomicsupf/iso-ktsp. 

PMID- 25578963
TI  - The ATP binding site of the chromatin remodeling homolog Lsh is required for
      nucleosome density and de novo DNA methylation at repeat sequences.
AB  - Lsh, a chromatin remodeling protein of the SNF2 family, is critical for normal
      heterochromatin structure. In particular, DNA methylation at repeat elements, a
      hallmark of heterochromatin, is greatly reduced in Lsh(-/-) (KO) cells. Here, we
      examined the presumed nucleosome remodeling activity of Lsh on chromatin in the
      context of DNA methylation. We found that dynamic CG methylation was dependent on
      Lsh in embryonic stem cells. Moreover, we demonstrate that ATP function is
      critical for de novo methylation at repeat sequences. The ATP binding site of Lsh
      is in part required to promote stable association of the DNA methyltransferase 3b
      with the repeat locus. By performing nucleosome occupancy assays, we found
      distinct nucleosome occupancy in KO ES cells compared to WT ES cells after
      differentiation. Nucleosome density was restored to wild-type level by re
      expressing wild-type Lsh but not the ATP mutant in KO ES cells. Our results
      suggest that ATP-dependent nucleosome remodeling is the primary molecular
      function of Lsh, which may promote de novo methylation in differentiating ES
      cells. 

PMID- 25578964
TI  - Transient DNMT1 suppression reveals hidden heritable marks in the genome.
AB  - Genome-wide demethylation and remethylation of DNA during early embryogenesis is
      essential for development. Imprinted germline differentially methylated domains
      (gDMDs) established by sex-specific methylation in either male or female germ
      cells, must escape these dynamic changes and sustain precise inheritance of both
      methylated and unmethylated parental alleles. To identify other, gDMD-like
      sequences with the same epigenetic inheritance properties, we used a modified
      embryonic stem (ES) cell line that emulates the early embryonic demethylation and
      remethylation waves. Transient DNMT1 suppression revealed gDMD-like sequences
      requiring continuous DNMT1 activity to sustain a highly methylated state.
      Remethylation of these sequences was also compromised in vivo in a mouse model of
      transient DNMT1 loss in the preimplantation embryo. These novel regions,
      possessing heritable epigenetic features similar to imprinted-gDMDs are required
      for normal physiological and developmental processes and when disrupted are
      associated with disorders such as cancer and autism spectrum disorders. This
      study presents new perspectives on DNA methylation heritability during early
      embryo development that extend beyond conventional imprinted-gDMDs. 

PMID- 25578965
TI  - Repressor activity of the RpoS/sigmaS-dependent RNA polymerase requires DNA
      binding.
AB  - The RpoS/sigma(S) sigma subunit of RNA polymerase (RNAP) activates transcription
      of stationary phase genes in many Gram-negative bacteria and controls adaptive
      functions, including stress resistance, biofilm formation and virulence. In this
      study, we address an important but poorly understood aspect of sigma(S)-dependent
      control, that of a repressor. Negative regulation by sigma(S) has been proposed
      to result largely from competition between sigma(S) and other sigma factors for
      binding to a limited amount of core RNAP (E). To assess whether sigma(S) binding
      to E alone results in significant downregulation of gene expression by other
      sigma factors, we characterized an rpoS mutant of Salmonella enterica serovar
      Typhimurium producing a sigma(S) protein proficient for Esigma(S) complex
      formation but deficient in promoter DNA binding. Genome expression profiling and
      physiological assays revealed that this mutant was defective for negative
      regulation, indicating that gene repression by sigma(S) requires its binding to
      DNA. Although the mechanisms of repression by sigma(S) are likely specific to
      individual genes and environmental conditions, the study of transcription
      downregulation of the succinate dehydrogenase operon suggests that sigma
      competition at the promoter DNA level plays an important role in gene repression
      by Esigma(S). 

PMID- 25578966
TI  - DICER-dependent biogenesis of let-7 miRNAs affects human cell response to DNA
      damage via targeting p21/p27.
AB  - Recently, it was reported that knockdown of DICER reduced the ATM-dependent DNA
      damage response and homologous recombination repair (HRR) via decreasing DICER
      generated small RNAs at the damage sites. However, we found that knockdown of
      DICER dramatically increased cell resistance to camptothecin that induced damage
      required ATM to facilitate HRR. This phenotype is due to a prolonged G1/S
      transition via decreasing DICER-dependent biogenesis of miRNA let-7, which
      increased the p21(Waf1/Cip1)/p27(Kip1) levels and resulted in decreasing the HRR
      efficiency. These results uncover a novel function of DICER in regulating the
      cell cycle through miRNA biogenesis, thus affecting cell response to DNA damage. 

PMID- 25578967
TI  - Protein mistranslation protects bacteria against oxidative stress.
AB  - Accurate flow of genetic information from DNA to protein requires faithful
      translation. An increased level of translational errors (mistranslation) has
      therefore been widely considered harmful to cells. Here we demonstrate that
      surprisingly, moderate levels of mistranslation indeed increase tolerance to
      oxidative stress in Escherichia coli. Our RNA sequencing analyses revealed that
      two antioxidant genes katE and osmC, both controlled by the general stress
      response activator RpoS, were upregulated by a ribosomal error-prone mutation.
      Mistranslation-induced tolerance to hydrogen peroxide required rpoS, katE and
      osmC. We further show that both translational and post-translational regulation
      of RpoS contribute to peroxide tolerance in the error-prone strain, and a small
      RNA DsrA, which controls translation of RpoS, is critical for the improved
      tolerance to oxidative stress through mistranslation. Our work thus challenges
      the prevailing view that mistranslation is always detrimental, and provides a
      mechanism by which mistranslation benefits bacteria under stress conditions. 

PMID- 25578970
TI  - The ATP-mediated formation of the YgjD-YeaZ-YjeE complex is required for the
      biosynthesis of tRNA t6A in Escherichia coli.
AB  - The essential and universal N(6)-threonylcarbamoyladenosine (t(6)A) modification
      at position 37 of ANN-decoding tRNAs plays a pivotal role in translational
      fidelity through enhancement of the cognate codon recognition and stabilization
      of the codon-anticodon interaction. In Escherichia coli, the YgjD (TsaD), YeaZ
      (TsaB), YjeE (TsaE) and YrdC (TsaC) proteins are necessary and sufficient for the
      in vitro biosynthesis of t(6)A, using tRNA, ATP, L-threonine and bicarbonate as
      substrates. YrdC synthesizes the short-lived L-threonylcarbamoyladenylate (TCA),
      and YgjD, YeaZ and YjeE cooperate to transfer the L-threonylcarbamoyl-moiety from
      TCA onto adenosine at position 37 of substrate tRNA. We determined the crystal
      structure of the heterodimer YgjD-YeaZ at 2.3 A, revealing the presence of an
      unexpected molecule of ADP bound at an atypical site situated at the YgjD-YeaZ
      interface. We further showed that the ATPase activity of YjeE is strongly
      activated by the YgjD-YeaZ heterodimer. We established by binding experiments and
      SAXS data analysis that YgjD-YeaZ and YjeE form a compact ternary complex only in
      presence of ATP. The formation of the ternary YgjD-YeaZ-YjeE complex is required
      for the in vitro biosynthesis of t(6)A but not its ATPase activity. 

PMID- 25578971
TI  - Inhibition of fibrous adhesion formation in the temporomandibular joint of
      tenascin-C knockout mice.
AB  - Tenascin-C (TNC) is a large hexameric extracellular matrix glycoprotein that is
      expressed in developing organs and tumors. It has been reported that TNC is
      expressed in inflamed synovial membranes and deformed discs of temporomandibular
      joint (TMJ) disorder. However, the role of TNC in TMJ is not fully known. In this
      study, the role of TNC in fibrous adhesion formation of TMJ was examined using
      TNC knockout (TNCKO) mice. Hypermobility was produced by excessive mouth opening
      method on the TMJ of both wild-type (WT) and TNCKO mice. TMJ wound healing was
      compared histologically, and the expression of TNC, fibronectin (FN) and alpha
      smooth muscle actin (alpha-SMA) in the wounded TMJ was examined by
      immunohistochemical and immunoblot analyses. Based on histologic analysis,
      fibrous adhesions were observed in the TMJ of both TNCKO and wild-type (WT) mice
      after excessive mouth opening. However, fibrous adhesion formation in TNCKO mice
      occurred later than in WT mice. TNC was expressed in the wounded TMJ disc and
      mandibular fossa. Although FN and alpha-SMA expression in the TMJ of TNCKO and WT
      mice was up-regulated after excessive mouth opening, FN and alpha-SMA protein
      levels were higher in WT mice at the same time points. In the wounded TMJ, TNC
      appears to enhance the expression of FN and alpha-SMA, and a lack of TNC may
      reduce fibrous adhesion formation in the TMJ. TNC plays an important role in TMJ
      wound healing, especially for wounds generated by mechanical stress. 

PMID- 25578968
TI  - Two novel NAC transcription factors regulate gene expression and flowering time
      by associating with the histone demethylase JMJ14.
AB  - The histone demethylase JMJ14 catalyzes histone demethylation at lysine 4 of
      histone 3 and is involved in transcriptional repression and flowering time
      control in Arabidopsis. Here, we report that JMJ14 is physically associated with
      two previously uncharacterized NAC transcription factors, NAC050 and NAC052. The
      NAC050/052-RNAi plants and the CRISPR-CAS9-mediated nac050/052 double mutant
      plants show an early flowering phenotype, which is similar to the phenotype of
      jmj14, suggesting a functional association between JMJ14 and NAC050/052. RNA-seq
      data indicated that hundreds of common target genes are co-regulated by JMJ14 and
      NAC50/052. Our ChIP analysis demonstrated that JMJ14 and NAC050 directly bind to
      co-upregulated genes shared in jmj14 and NAC050/052-RNAi, thereby facilitating
      H3K4 demethylation and transcriptional repression. The NAC050/052 recognition DNA
      cis-element was identified by an electrophoretic mobility shift assay at the
      promoters of its target genes. Together, our study identifies two novel NAC
      transcription repressors and demonstrates that they are involved in
      transcriptional repression and flowering time control by associating with the
      histone demethylase JMJ14. 

PMID- 25578973
TI  - Assessment of the Selenoprotein M (SELM) over-expression on human hepatocellular
      carcinoma tissues by immunohistochemistry.
AB  - Selenium is an essential trace mineral of fundamental importance to human healthy
      and exerts its biological function through selenoproteins. In particular,
      Selenoprotein M (SELM) is located in the endoplasmic reticulum and contains the
      common redox motif of cysteine-X-X-selenocysteine type. It attracts great
      attention due to its high expression in brain and its potential roles as
      antioxidant, neuroprotective, and cytosolic calcium regulator. Recently, our
      group found SELM over-expression  in human hepatocellular carcinoma (HCC) cell
      lines. In this report some paraffin-embedded tissues from liver biopsy of
      patients with hepatitis C virus (HCV)-related cirrhosis and HCC were
      immunohistochemically stained and SELM expression scoring was evaluated. Our
      results evidence for the first time an increase of SELM expression in HCC liver
      tissues, and its gradual expression raise associated with an increased malignancy
      grade. Therefore, we propose to use i) SELM as putative marker for HCC as well as
      ii) simple immunohistochemistry technique to distinguish between the different
      grades of malignancy.  

PMID- 25578972
TI  - Immunocytochemical detection of dentin matrix proteins in primary teeth from
      patients with dentinogenesis imperfecta associated with osteogenesis imperfecta.
AB  - Dentinogenesis imperfecta determines structural alterations of the collagen
      structure still not completely elucidated. Immunohistochemical analysis was used
      to assay Type I and VI collagen, various non-collagenous proteins distribution in
      human primary teeth from healthy patients or from patients affected by type I
      dentinogenesis imperfecta (DGI-I) associated with osteogenesis imperfecta (OI).
      In sound primary teeth, an organized well-known ordered pattern of the type I
      collagen fibrils was found, whereas atypical and disorganized fibrillar
      structures were observed in dentin of DGI-I affected patients. Expression of type
      I collagen was observed in both normal and affected primary teeth, although
      normal dentin stained more uniformly than DGI-I affected dentin. Reactivity of
      type VI collagen was significantly lower in normal teeth than in dentin from DGI
      I affected patients (P<0.05). Expressions of dentin matrix protein (DMP)-1 and
      osteopontin (OPN) were observed in both normal dentin and dentin from DGI-I
      affected patients, without significant differences, being DMP1 generally more
      abundantly expressed. Immunolabeling for chondroitin sulfate (CS) and biglycan
      (BGN) was weaker in dentin from DGI-I-affected patients compared to normal
      dentin, this decrease being significant only for CS. This study shows
      ultrastructural alterations in dentin obtained from patients affected by DGI-I,
      supported by immunocytochemical assays of different collagenous and non
      collagenous proteins. 

PMID- 25578969
TI  - DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer
      sequences by SOX2 and PAX6 transcription factors.
AB  - Sox2 and Pax6 are transcription factors that direct cell fate decision during
      neurogenesis, yet the mechanism behind how they cooperate on enhancer DNA
      elements and regulate gene expression is unclear. By systematically interrogating
      Sox2 and Pax6 interaction on minimal enhancer elements, we found that cooperative
      DNA recognition relies on combinatorial nucleotide switches and precisely spaced,
      but cryptic composite DNA motifs. Surprisingly, all tested Sox and Pax paralogs
      have the capacity to cooperate on such enhancer elements. NMR and molecular
      modeling reveal very few direct protein-protein interactions between Sox2 and
      Pax6, suggesting that cooperative binding is mediated by allosteric interactions
      propagating through DNA structure. Furthermore, we detected and validated several
      novel sites in the human genome targeted cooperatively by Sox2 and Pax6.
      Collectively, we demonstrate that Sox-Pax partnerships have the potential to
      substantially alter DNA target specificities and likely enable the pleiotropic
      and context-specific action of these cell-lineage specifiers. 

PMID- 25578974
TI  - Premature senescence in primary muscle cultures of myotonic dystrophy type 2 is
      not associated with p16 induction.
AB  - Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are multisystemic disorders
      linked to two different genetic loci and characterized by several features
      including myotonia, muscle weakness and atrophy, cardiac dysfunctions, cataracts
      and insulin-resistance. In both forms, expanded nucleotide sequences cause the
      accumulation of mutant transcripts in the nucleus deregulating the activity of
      some RNAbinding proteins and providing an explanation for the multisystemic
      phenotype of DM patients. However this pathogenetic mechanism does not explain
      some histopathological features of DM skeletal muscle like muscle atrophy. It has
      been observed that DM muscle shares similarities with the ageing muscle, where
      the progressive muscle weakness and atrophy is accompanied by a lower
      regenerative capacity possibly due to the failure in satellite cells activation.
      The aim of our study is to investigate if DM2 satellite cell derived myoblasts
      exhibit a premature senescence as reported for DM1 and if alterations in their
      proliferation potential and differentiation capabilities might contribute to some
      of the histopathological features observed in DM2 muscles. Our results indicate
      that DM myoblasts have lower proliferative capability than control myoblasts and
      reach in vitro senescence earlier than controls. Differentely from DM1, the p16
      pathway is not responsible for the premature growth arrest observed in DM2
      myoblasts which stop dividing with telomeres shorter than controls. During in
      vitro senescence, a progressive decrease in fusion index is observable in both DM
      and control myotubes with no significant differences between groups. Moreover,
      myotubes obtained from senescent myoblasts appear to be smaller than those from
      young myoblasts. Taken together, our data indicate a possible role of DM2
      premature myoblast senescence in skeletal muscle histopathological alterations
      i.e., dystrophic changes and type 2 fibre atrophy. 

PMID- 25578975
TI  - Wheat germ agglutinin staining as a suitable method for detection and
      quantification of fibrosis in cardiac tissue after myocardial infarction.
AB  - The quantification of fibrotic tissue is an important task in the analysis of
      cardiac remodeling. The use of established fibrosis staining techniques is
      limited on frozen cardiac tissue sections due to a reduced color contrast
      compared to paraffin embedded sections. We therefore used FITC-labeled wheat germ
      agglutinin (WGA), which marks fibrotic tissue in comparable quality as the
      established picrosirius red (SR) staining, for the staining of post myocardial
      infarction scar tissue. The fibrosis amount was quantified in a histogram-based
      approach using the non-commercial image processing program ImageJ. Our results
      clearly demonstrate that WGA-FITC is a suitable marker for cardiac fibrosis in
      frozen tissue sections. In combination with the histogram-based analysis, this
      new quantification approach is i) easy and fast to perform; ii) suitable for raw
      frozen tissue sections; and iii) allows the use of additional antibodies in co
      immunostaining.  

PMID- 25578976
TI  - Visualizing endocytotic pathways at transmission electron microscopy via
      diaminobenzidine photo-oxidation by a fluorescent cell-membrane dye.
AB  - The endocytotic pathway involves a complex, dynamic and interacting system of
      intracellular compartments. PKH26 is a fluorescent dye specific for long-lasting
      cell membrane labelling which has been successfully used for investigating cell
      internalization processes, at either flow cytometry or fluorescence microscopy.
      In the present work, diaminobenzidine photo-oxidation was tested as a procedure
      to detect PKH26 dye at transmission electron microscopy. Our results demonstrated
      that DAB-photo-oxidation is a suitable technique to specifically visualise this
      fluorescent dye at the ultrastructural level: the distribution of the granular
      dark reaction product perfectly matches the pattern of the fluorescence staining,
      and the electron density of the fine precipitates makes the signal evident and
      precisely detectable on the different subcellular compartments involved in the
      plasma membrane internalization routes. 

PMID- 25578977
TI  - Histochemical and biometric study of the gastrointestinal system of Hyla
      orientalis (Bedriaga, 1890) (Anura, Hylidae).
AB  - This study was carried out to assess the localization of hyaluronic acid (HA) and
      the distribution of glycoproteins in the gastrointestinal system of adult Hyla
      orientalis. Histochemical analysis of the gastrointestinal system in H.
      orientalis showed that mucous content included glycogene and/or oxidable dioles
      [periodic acid/Schiff (PAS)+], neutral or acid-rich (PAS/AB pH 2.5+), sialic acid
      residues (KOH/PAS+) and acid sulphate [Aldehyde fuchsin (AF)+] glycoproteins.
      However the mucus content was not the same in stomach, small and large intestine.
      The mucus content of stomach included only glycogene and/or oxidable dioles and
      sialic acid residues. Besides these histochemical methods, the localization of HA
      was detected using biotinylated hyaluronic acid binding protein labeled with
      streptavidin-fluorescein isothiocyanate (FITC). In the extracellular matrix of
      the submucosa, the reaction for HA was evident. Since HA was located in submucosa
      beneath the epithelial layer of gastrointestinal system, it has a significant
      role in hydric balance, and essential to provide the gastrointestinal system
      integrity and functionality. According to biometric results, there were
      statistical differences between small and large intestine in terms of the amount
      of material stained positive with PAS/AB, PAS, KOH/PAS and AF/AB. Additionally,
      number of goblet cells in the small and large intestine was significantly
      different. 

PMID- 25578978
TI  - Specific association of growth-associated protein 43 with calcium release units
      in skeletal muscles of lower vertebrates.
AB  - Growth-associated protein 43 (GAP43), is a strictly conserved protein among
      vertebrates implicated in neuronal development and neurite branching. Since GAP43
      structure contains a calmodulin-binding domain, this protein is able to bind
      calmodulin and gather it nearby membrane network, thus regulating cytosolic
      calcium and consequently calcium-dependent intracellular events. Even if for many
      years GAP43 has been considered a neuronal-specific protein, evidence from
      different laboratories described its presence in myoblasts, myotubes and adult
      skeletal muscle fibers. Data from our laboratory showed that GAP43 is localized
      between calcium release units (CRUs) and mitochondria in mammalian skeletal
      muscle suggesting that, also in skeletal muscle, this protein can be a key player
      in calcium/calmodulin homeostasis. However, the previous studies could not
      clearly distinguish between a mitochondrion- or a triad-related positioning of
      GAP43. To solve this question, the expression and localization of GAP43 was
      studied in skeletal muscle of Xenopus and Zebrafish known to have triads located
      at the level of the Z-lines and mitochondria not closely associated with them.
      Western blotting and immunostaining experiments revealed the expression of GAP43
      also in skeletal muscle of lower vertebrates (like amphibians and fishes), and
      that the protein is localized closely to the triad junction. Once more, these
      results and GAP43 structural features, support an involvement of the protein in
      the dynamic intracellular Ca2+ homeostasis, a common conserved role among the
      different species. 

PMID- 25578979
TI  - Contribution of intestinal smooth muscle to Crohn's disease fibrogenesis.
AB  - Mesenchymal cells transdifferentiation and extracellular matrix deposition are
      involved in the fibrotic process of Crohn's disease (CD). Mesenchymal smooth
      muscle cells (SMCs) de-differentiation, driven by Platelet-derived growth factor
      (PDGF) that counteracts Transforming growth factor (TGF-beta) has been studied in
      vascular muscle. The role of SMCs in intestinal fibrogenesis is still not clearly
      elucidated. Aim of the study was to evaluate the possible myogenic contribution
      to CD fibrotic process through the comparative analysis of histological,
      morphometric and molecular alterations occurring in human smooth muscle. Full
      thickness specimens were obtained from CD (non-involved and stenotic tracts) and
      healthy (control) ileum. Tissues were processed for histological and
      immunohistochemical (IHC) analyses and SMCs were isolated from the muscularis
      propria for morphofunctional and molecular (qPCR) analyses. CD stenotic ileum
      showed a significant increased thickness of all layers compared to CD non
      involved and control ileum. IHC revealed an overexpression of alpha-smooth muscle
      actin and collagens I-III throughout all intestinal layers only in stenotic
      tracts. The two growth factors, PDGF and TGF-beta, showed a progressive increase
      in expression in the muscle layer from CD non-involved to stenotic tracts.
      Freshly isolated SMCs presented alterations in CD non-involved tracts that
      progressively increased in the stenotic tracts consisting in a statistical
      increase in mRNA encoding for PDGF-beta and collagen III, paralleled to a
      decrease in TGF-beta and Tribbles-like protein-3 mRNA, and altered
      morphofunctional parameters consisting in progressive decreases in cell length
      and contraction to acetylcholine. These findings indicate that intrinsic myogenic
      alterations occur in CD ileum, that they likely precede stricture formation, and
      might represent suitable new targets for anti-fibrotic interventions. 

PMID- 25578982
TI  - Association of heat shock protein 90 with motility of post-thawed sperm in bulls.
AB  - The correlation between the 90 kDa heat-shock protein (HSP90) and sperm quality
      following the process of freezing-thawing in bulls has not been studied clearly.
      Therefore, the objective of the present was to clarify the relationship between
      HSP90 level and semen parameters during the process of cryopreservation in bulls.
      Semen samples from 5 Holstein bulls were obtained by artificial vagina.
      Characteristics of these semen at three stages (fresh, after equilibration and
      frozen-thawed), including motility, plasma membrane integrity and acrosome
      integrity were evaluated. The mRNA expression level of HSP90 at the three stages
      was evaluated by using quantitative Real-Time PCR. Meanwhile, the protein level
      of HSP90 expression at the three stages was detected according to Western blot.
      The results showed that sperm parameters evaluated in fresh semen was the highest
      in the three groups. Sperm parameters in semen after equilibration were lower
      than those in fresh semen (P>0.05) and higher than those in post-thawed semen
      (P<0.05). Sperm parameters in frozen-thawed semen were the lowest among the three
      groups (P<0.05). This study indicated that HSP90 expression is proportional to
      sperm quality. HSP90 expression level in fresh semen was significantly higher
      than that in frozen-thawed semen (P<0.05). Although no significant differences in
      HSP90 expression were observed between fresh semen and semen after equilibration
      (P>0.05). Results in this study suggest that HSP90 level in bull spermatozoa was
      gradually declined following the process of freezing-thawing, and might be
      associated with sperm motility, plasma membrane integrity and acrosome integrity.

PMID- 25578983
TI  - Validation of four measures of mental health against depression and generalized
      anxiety in a community based sample.
AB  - There is a need to validate screening measures of affective and generalized
      anxiety disorders for use in epidemiological surveys of mental health in the
      general population. This study examined the diagnostic accuracy of the Patient
      Health Questionnaire (PHQ-9), Goldberg Anxiety and Depression Scales (GAS, GDS)
      and the 12-item Short Form Health Survey (SF-12) Mental Health Component Summary
      Scale (MCS-12) in a population based longitudinal study in Australia. We report
      analyses of two narrow age birth cohorts in the Personality and Total Health
      (PATH) through life study (ages 32-36 and 52-58). Depressive episodes (severe,
      moderate, and mild), dysthymia and generalized anxiety disorder were diagnosed
      according to International Classification of Diseases (ICD-10) criteria using the
      World Health Organisation (WHO) Composite International Diagnostic Interview
      (CIDI) as a criterion. All scales had high concordance with their target 30-day
      diagnoses, with area under the Receiver Operating Characteristic (ROC) curve
      (AUC) ranging between 0.85 and 0.90. The PHQ-9, GDS, GAS and MCS-12 were all
      valid instruments for identifying possible cases of depression and anxiety, and
      assessing the severity of these common mental disorders in the general
      population. We report recommended cut-points for each scale, though note that the
      optimal cut-point on mental health screening instruments may vary depending on
      the context of test administration. 

PMID- 25578981
TI  - Impact of Histochemistry on biomedical research: looking through the articles
      published in a long-established histochemical journal.
AB  - Histochemistry provides the unique opportunity to detect single molecules in the
      very place where they exert their structural roles or functional activities: this
      makes it possible to correlate structural organization and function, and may be
      fruitfully exploited in countless biomedical research topics. Aiming to estimate
      the impact of histochemical articles in the biomedical field, the last few years
      citations of articles published in a long-established histochemical journal have
      been considered. This brief survey suggests that histochemical journals,
      especially the ones open to a large spectrum of research subjects, do represent
      an irreplaceable source of information not only for cell biologists,
      microscopists or anatomists, but also for biochemists, molecular biologists and
      biotechnologists. 

PMID- 25578980
TI  - Autofluorescence spectroscopy and imaging: a tool for biomedical research and
      diagnosis.
AB  - Native fluorescence, or autofluorescence (AF), consists in the emission of light
      in the UV-visible, near-IR spectral range when biological substrates are excited
      with light at suitable wavelength. This is a well-known phenomenon, and the
      strict relationship of many endogenous fluorophores with morphofunctional
      properties of the living systems, influencing their AF emission features, offers
      an extremely powerful resource for directly monitoring the biological substrate
      condition. Starting from the last century, the technological progresses in
      microscopy and spectrofluorometry were convoying attention of the scientific
      community to this phenomenon. In the future, the interest in the autofluorescence
      will certainly continue. Current instrumentation and analytical procedures will
      likely be overcome by the unceasing progress in new devices for AF detection and
      data interpretation, while a progress is expected in the search and
      characterization of endogenous fluorophores and their roles as intrinsic
      biomarkers. 

PMID- 25578984
TI  - Carbohydrates as new probes for the identification of closely related Escherichia
      coli strains using surface plasmon resonance imaging.
AB  - Prevention of foodborne diseases depends highly on our ability to control rapidly
      and accurately a possible contamination of food. So far, standard procedures for
      bacterial detection require time-consuming bacterial cultures on plates before
      the pathogens can be detected and identified. We present here an innovative
      biochip, based on direct differential carbohydrate recognitions of five closely
      related Escherichia coli strains, including the enterohemorragic E. coli O157:H7.
      Our device relies on efficient grafting of simple carbohydrates on a gold surface
      and on the monitoring of their interactions with bacteria during their culture
      using surface plasmon resonance imaging. We show that each of the bacteria
      interacts in a different way with the carbohydrate chip. This allows the
      detection and discrimination of the tested bacterial strains in less than 10 h
      from an initial bacterial concentration of 10(2) CFU.mL(-1). This is an
      improvement over previously described systems in terms of cost, easiness to use,
      and stability. Easily conceived and easily regenerated, this tool is promising
      for the future of food safety. 

PMID- 25578990
TI  - Understanding the composition-structure-bioactivity relationships in diopside
      (CaO.MgO.2SiO2)-tricalcium phosphate (3CaO.P2O5) glass system.
AB  - The present work is an amalgamation of computation and experimental approach to
      gain an insight into composition-structure-bioactivity relationships of alkali
      free bioactive glasses in the CaO-MgO-SiO2-P2O5 system. The glasses have been
      designed in the diopside (CaO.MgO.2SiO2; Di)-tricalcium phosphate (3CaO.P2O5;
      TCP) binary join by varying the Di/TCP ratio. The melt-quenched glasses have been
      investigated for their structure by molecular dynamic (MD) simulations as well as
      by nuclear magnetic resonance spectroscopy (NMR). In all the investigated glasses
      silicate and phosphate components are dominated by Q(2) (Si) and Q(0) (P)
      species, respectively. The apatite forming ability of the glasses was
      investigated using X-ray diffraction (XRD), infrared spectroscopy after immersion
      of glass powders in simulated body fluid (SBF) for time durations varying between
      1 h and 14 days, while their chemical degradation has been studied in Tris-HCl in
      accordance with ISO 10993-14. All the investigated glasses showed good
      bioactivity without any substantial variation. A significant statistical increase
      in metabolic activity of human mesenchymal stem cells (hMSCs) when compared to
      the control was observed for Di-60 and Di-70 glass compositions under both basal
      and osteogenic conditions.

PMID- 25578991
TI  - Assessment of registration accuracy during computer-aided oncologic limb-salvage
      surgery.
AB  - PURPOSE: Computer-aided surgery is used in musculoskeletal tumor procedures to
      improve the surgeon's orientation to local anatomy during tumor resection. For
      the navigation system to function correctly, preoperative imaging (e.g., CT, MR)
      must be registered to the patient in the operating room. The goals of this study
      were (1) to directly quantify registration accuracy in computer-aided tumor
      surgery and (2) to validate the "system reported error" (SRE) of the navigation
      system. METHODS: Registration accuracy was evaluated in eight bone sarcoma cases
      by determining the location of the anatomical paired-points used for registration
      following surface matching. Coordinates of specific intraoperative post
      registration points were compared with the corresponding coordinates in
      preoperative CT scans to determine the measurement error (ME). RESULTS: The mean
      difference between post-registration points and planned registration points was
      12.21+/-6.52 mm significantly higher than the mean SRE (0.68 +/- 0.15 mm; p =
      0.002; 95 % CI 6.11-16.96 mm). The SRE poorly correlated with the calculated ME
      (R(2) = 0.040). Anatomical paired-point registration with surface matching
      results in a substantial shift in the post-registration coordinates of the same
      paired-points used for registration, and this shift is not represented by the
      SRE. CONCLUSION: The SRE of a surgical navigation system was poorly correlated
      with direct measurements obtained in musculoskeletal tumor surgery. Improvement
      in registration accuracy is needed to better navigate tumor boundaries and ensure
      clear margins while maximally preserving the unaffected tissues and reducing
      operative morbidity.

PMID- 25578992
TI  - CPU-GPU mixed implementation of virtual node method for real-time interactive
      cutting of deformable objects using OpenCL.
AB  - PURPOSE: Surgical simulators need to simulate interactive cutting of deformable
      objects in real time. The goal of this work was to design an interactive cutting
      algorithm that eliminates traditional cutting state classification and can work
      simultaneously with real-time GPU-accelerated deformation without affecting its
      numerical stability. METHODS: A modified virtual node method for cutting is
      proposed. Deformable object is modeled as a real tetrahedral mesh embedded in a
      virtual tetrahedral mesh, and the former is used for graphics rendering and
      collision, while the latter is used for deformation. Cutting algorithm first
      subdivides real tetrahedrons to eliminate all face and edge intersections, then
      splits faces, edges and vertices along cutting tool trajectory to form cut
      surfaces. Next virtual tetrahedrons containing more than one connected real
      tetrahedral fragments are duplicated, and connectivity between virtual
      tetrahedrons is updated. Finally, embedding relationship between real and virtual
      tetrahedral meshes is updated. Co-rotational linear finite element method is used
      for deformation. Cutting and collision are processed by CPU, while deformation is
      carried out by GPU using OpenCL. RESULTS: Efficiency of GPU-accelerated
      deformation algorithm was tested using block models with varying numbers of
      tetrahedrons. Effectiveness of our cutting algorithm under multiple cuts and self
      intersecting cuts was tested using a block model and a cylinder model. Cutting of
      a more complex liver model was performed, and detailed performance
      characteristics of cutting, deformation and collision were measured and analyzed.
      CONCLUSIONS: Our cutting algorithm can produce continuous cut surfaces when
      traditional minimal element creation algorithm fails. Our GPU-accelerated
      deformation algorithm remains stable with constant time step under multiple
      arbitrary cuts and works on both NVIDIA and AMD GPUs. GPU-CPU speed ratio can be
      as high as 10 for models with 80,000 tetrahedrons. Forty to sixty percent real
      time performance and 100-200 Hz simulation rate are achieved for the liver model
      with 3,101 tetrahedrons. Major bottlenecks for simulation efficiency are cutting,
      collision processing and CPU-GPU data transfer. Future work needs to improve on
      these areas.

PMID- 25578993
TI  - Direction of Apt test modification: sensitivity and simplicity.

PMID- 25578995
TI  - Reply: To PMID 24976330.

PMID- 25578994
TI  - Environmental rather than genetic factors determine the variation in the age of
      the infancy to childhood transition: a twins study.
AB  - OBJECTIVE: Using a twins study, we sought to assess the contribution of genetic
      against environmental factor as they affect the age at transition from infancy to
      childhood (ICT). STUDY DESIGN: The subjects were 56 pairs of monozygotic twins,
      106 pairs of dizygotic twins, and 106 pairs of regular siblings (SBs), for a
      total of 536 children. Their ICT was determined, and a variance component
      analysis was implemented to estimate components of the familial variance, with
      simultaneous adjustment for potential covariates. RESULTS: We found substantial
      contribution of the common environment shared by all types of SBs that explained
      27.7% of the total variance in ICT, whereas the common twin environment explained
      9.2% of the variance, gestational age 3.5%, and birth weight 1.8%. In addition,
      8.7% was attributable to sex difference, but we found no detectable contribution
      of genetic factors to inter-individual variation in ICT age. CONCLUSIONS:
      Developmental plasticity impacts much of human growth. Here we show that of the
      ~50% of the variance provided to adult height by the ICT, 42.2% is attributable
      to adaptive cues represented by shared twin and SB environment, with no
      detectable genetic involvement.

PMID- 25578996
TI  - Striking striae from "triple-threat" lotion.

PMID- 25578998
TI  - Cladding layer on well-defined double-wall TiO2 nanotubes.
AB  - Highly ordered double-wall TiO2 nanotube arrays were obtained by a two-step
      anodization method in a fluoride-containing glycerol based electrolyte. The low
      water and fluoride content and high viscosity of the electrolyte support a partly
      undissolved fluoride-rich layer, and its hydrolyzed products remain on the tube
      walls. The double-wall structure and a cladding layer originating from the
      fluoride-rich layer were clearly observed after annealing. The morphology and
      crystal structure of the cladding layer were investigated. The study of the
      cladding layer gives a fundamental insight into the wall structure design of the
      anodic TiO2 nanotubes in the glycerol-based electrolyte. 

PMID- 25578997
TI  - Risk of congenital heart defects in the offspring of smoking mothers: a
      population-based study.
AB  - OBJECTIVES: To conduct a population-based study examining the occurrence of
      congenital heart defects (CHDs) in relation to maternal smoking during the first
      trimester of pregnancy. STUDY DESIGN: This retrospective case-control study used
      Washington State birth certificates from 1989 to 2011 and linked hospital
      discharge International Classification of Diseases, 9th revision, codes to
      identify singleton nonsyndromic CHD cases and determine maternal prenatal smoking
      status. We calculated ORs from multivariate logistic regression models to compare
      maternal first-trimester smoking status (any and daily number of cigarettes)
      among 14,128 cases, both overall and by phenotype, and 60,938 randomly selected
      controls frequency matched on birth year. RESULTS: Offspring of mothers reporting
      cigarette use in the first trimester of pregnancy were more likely to be born
      with a CHD (aOR 1.16 [1.08-1.24]) independent of demographic characteristics and
      other prenatal risk factors for CHDs. Maternal smoking was most strongly
      associated with pulmonary valve anomalies (aOR 1.48 [95% CI: 1.15-1.90]),
      pulmonary artery anomalies (aOR 1.71 [1.40-2.09]), and isolated atrial septal
      defects (aOR 1.22 [1.08-1.38]). The association between maternal smoking and CHDs
      was stronger with increasing number of daily cigarettes and among older (35+
      years) mothers compared with younger mothers. CONCLUSIONS: We provide evidence
      that maternal smoking during pregnancy is a risk factor for select CHD
      phenotypes. Maternal smoking may account for 1.4% of all CHDs. New findings
      include a strong dose-dependence of the association and augmented risk in older
      mothers.

PMID- 25579003
TI  - Certification of head and neck oncologic surgeons--a new day.

PMID- 25579002
TI  - Strong induction of iodothyronine deiodinases by chemotherapeutic
      selenocompounds.
AB  - The biological activity of thyroid hormones (TH) is regulated by selenoenzymes of
      the iodothyronine deiodinase (DIO) family catalysing TH activating and
      inactivating reactions. Besides TH metabolism, several studies indicate an
      important role of DIO isoenzymes in tumorigenesis and cancer growth. It is
      therefore of therapeutic importance to identify modulators of DIO expression. We
      have synthesized and studied a series of selenocompounds containing a methyl- or
      benzyl-imidoselenocarbamate backbone. One of these novel compounds had
      chemotherapeutic activities in a murine xenograft tumour model by an unknown
      mechanism. Therefore, we tested their effects on DIO expression in vitro. In
      HepG2 hepatocarcinoma cells, DIO1 activity was strongly (up to 10-fold) increased
      by the methyl- but not by the corresponding benzyl-imidoselenocarbamates. Steady
      state mRNA levels remained unaltered under these conditions indicating a post
      transcriptional mode of action. The effects were further characterized in HEK293
      cells stably expressing DIO1, DIO2 or DIO3. Even within the artificial genetic
      context of the expression vectors, all three DIO isoenzymes were up-regulated by
      the methyl- and to a lesser extent by the benzyl-imidoselenocarbamates.
      Consistent stimulating effects were observed with methyl-N,N'-di(quinolin-3
      ylcarbonyl)-imidoselenocarbamate (EI201), a selenocompound known for its anti
      tumour activity. DIO inducing effects were unrelated to the intracellular
      accumulation of selenium, yet the precise mode of action remains elusive.
      Collectively, our data highlight that these selenocompounds may constitute
      interesting pharmacological compounds for modifying DIO expression potentially
      affecting the balance between cell differentiation and proliferation. 

PMID- 25579004
TI  - A recent situation.

PMID- 25579005
TI  - Management of tooth extraction in a patient with a rare bleeding disorder
      associated with Hermansky-Pudlak syndrome: a case report.
AB  - PURPOSE: This report describes the case of a 27-year-old man who had been
      diagnosed with Hermansky-Pudlak syndrome shortly after birth. Because the patient
      had a major bleeding disorder associated with his syndrome, local and systemic
      hemostatic protection recommendations had to be considered before tooth
      extraction. MATERIALS AND METHODS: Synthetic vasopressin (1-deamino-8-d-arginine
      vasopressin [DDAVP]) was transfused intravenously before surgery. During surgery
      the patient was transfused with 1 U of human leukocyte antigen (HLA)-matched
      apheresis platelets. A hemostatic packing of Avitene and Gelfoam was adapted to
      the extraction site. RESULTS: Treatment with DDAVP, HLA-matched platelets, and
      local application of a packing with Avitene and Gelfoam resulted in sustained
      hemostasis and an excellent healing response. CONCLUSION: Surgical and routine
      extractions appear to be safe procedures in patients with Hermansky-Pudlak
      syndrome when appropriate local and systemic hemostatic measures are used.

PMID- 25579006
TI  - Osteoarthritic changes after superior and inferior joint space injection of
      hyaluronic acid for the treatment of temporomandibular joint osteoarthritis with
      anterior disc displacement without reduction: a cone-beam computed tomographic
      evaluation.
AB  - PURPOSE: This study compared the effect of superior and inferior joint space
      injections of hyaluronic acid (HA) and evaluated osteoarthritic changes in
      patients diagnosed with temporomandibular joint (TMJ) anterior disc displacement
      without reduction (ADDw/oR) in association with osteoarthritis (OA) by cone-beam
      computed tomography (CBCT). MATERIALS AND METHODS: One hundred forty-one patients
      with research diagnostic criteria for ADDw/oR in association with TMJ OA were
      randomly assigned to 1 of 2 study groups that received superior or inferior joint
      space injection of HA. CBCT and clinical examination were performed before
      treatment and at 3 and 9 months after treatment. RESULTS: One hundred twenty-six
      patients returned for the 3-month evaluations, and 74 returned for the 9-month
      evaluations. Condylar remodeling and TMJ function showed improvement in most
      patients after treatment. At 3 months, remodeling scores in the superior and
      inferior groups were 2.14 +/- 3.16 and 4.08 +/- 3.82, respectively, and scores
      were 4.80 +/- 3.36 and 7.47 +/- 3.90 at 9 months. There were significant
      differences between the superior and inferior groups at 3 and 9 months after
      treatment (3-month, P = .002; 9-month, P = .002). The Helkimo index of the
      inferior group was significantly lower than that of superior group at 3 and 9
      months (3-month, P = .008; 9-month, P = .028). There were no significant
      differences in maximal mouth opening between the 2 groups at 3 and 9 months (3
      month, P = .82; 9-month, P = .20). CONCLUSION: Superior and inferior joint space
      injections of HA are effective methods for the treatment of ADDw/oR in
      association with TMJ OA. The injection of HA within the inferior joint space
      appears to result in better condylar reparative remodeling and improvement in jaw
      function.

PMID- 25579007
TI  - Imperforate titanium shell enclosing recombinant human bone morphogenetic protein
      2-induced bone formation for high-profile dental implants in rabbit tibia.
AB  - PURPOSE: To evaluate the use of a nonperforated titanium occlusive device over
      high-profile dental implants in rabbit tibia using recombinant human bone
      morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) for
      augmentation grafting. MATERIALS AND METHODS: Eight New Zealand white rabbits
      were used for the experiment. All rabbits underwent computed tomography of the
      right tibia. A custom titanium shell was manufactured for each rabbit using a
      computer-assisted design to confine the graft. Three high-profile implants were
      placed in the right tibia of each rabbit; the middle implant was placed 8 mm in
      supracrestal fashion and the adjacent implants were placed 5 mm in supracrestal
      fashion. There were 4 groups (n = 2 per group): non-shell control, titanium shell
      only, titanium shell over buffered collagen, and titanium shell over the ACS
      enriched with rhBMP-2. The animals were sacrificed after 6 or 12 weeks.
      Histologic preparation was carried out to evaluate bone formation. RESULTS: After
      6 weeks, negligible bone growth was found around the implants. After 12 weeks,
      there was minimal bone formation around the implants in the control group,
      whereas in the group treated with ACS enriched with rhBMP-2, the titanium shell
      was filled with mature bone, which was expressed at the implant surface, the
      shell's interior, and the exterior surfaces. CONCLUSION: The placement of ACS
      enriched with rhBMP-2 beneath an occlusive nonperforated titanium shell confining
      high-profile dental implants resulted in visibly more formation of mature bone.

PMID- 25579008
TI  - Mechanical versus biological stability of immediate and delayed implant placement
      using resonance frequency analysis.
AB  - PURPOSE: The purpose was to objectively measure the stability of immediately
      placed implants compared with implants placed at healed sites using implant
      stability quotient (ISQ) values obtained by resonance frequency analysis.
      MATERIALS AND METHODS: Data were collected from 137 Nobel Replace Tapered Groovy
      Implants placed in 85 patients 19 to 93 years old. All implants were placed by
      the same surgeon from May 2007 to October 2011. Forty-one implants were placed
      immediately after extraction with MasterGraft bone grafting material and 96 were
      placed in healed sites with no grafting material. ISQ values obtained by the
      Osstell ISQ System were recorded at the time of implant placement and at a
      subsequent follow-up appointment (T2). T2 was split into 2- to 3-month and 4- to
      6-month groups depending on when their follow-up ISQ values were obtained. Data
      were analyzed using simple linear regression. RESULTS: Implants placed in healed
      sites had higher average ISQ values at implant placement compared with
      immediately placed implants; however, mean ISQ values in the 2 immediate implant
      groups exceeded the ISQ threshold of 65. Immediately placed implants in the 2- to
      3-month and 4- to 6-month groups had average ISQ values of 65.60 and 68.65,
      respectively, whereas implants placed in healed sites had averages of 76.73 (2-
      to 3-month group) and 71.23 (4- to 6-month group). These differences were
      statistically significant (P < .05). At subsequent follow-up appointments,
      implants placed in healed sites had higher mean ISQ values. Implants in healed
      sites had ISQ averages of 79.58 (2- to 3-month group) and 77.31 (4- to 6-month
      group), whereas immediately placed implants had averages of 73.88 and 70.14.
      These differences were statistically significant (P < .05). Moreover, these mean
      ISQ values in immediate implants exceeded the ISQ threshold of 65. CONCLUSION:
      Although mean ISQ values of immediately placed implants are lower than those of
      delayed implants at implant placement and follow-up appointments, immediate
      implant mean ISQ values consistently remain higher than the clinically successful
      ISQ threshold of 65 throughout the osseointegration process. These results
      support the immediate placement of implants in extraction sockets under favorable
      conditions.

PMID- 25579009
TI  - Interleukin 17A and interleukin 17F polymorphisms are associated with oral
      squamous cell carcinoma susceptibility in a Chinese population.
AB  - PURPOSE: Several studies have investigated the association of the interleukin
      (IL) 17A and IL-17F polymorphisms and cancer of various organs. However, the role
      of the IL-17A and IL-17F polymorphisms in oral squamous cell carcinoma (OSCC)
      remains unclear. Thus we sought to clarify the association of the rs2275913,
      rs763780, and rs2397084 polymorphisms with OSCC in a Chinese population.
      MATERIALS AND METHODS: A TaqMan single-nucleotide polymorphism Genotyping Assay
      (ABI, Foster, CA) was used to measure the distributions of the IL-17A (rs2275913)
      and IL-17F (rs763780, rs2397084) polymorphisms in 121 OSCC patients and 103
      healthy controls. The association of those polymorphisms and clinical OSCC
      patient characteristic also was evaluated. RESULTS: Individuals carrying the
      rs2275913 A allele and AA genotype had an increased risk of OSCC (odds ratio
      [OR], 1.463; 95% confidence interval [CI], 0.807 to 2.652; and OR, 2.713; 95% CI,
      1.250 to 5.889, respectively). The frequency of the rs2397084 T allele was
      significantly associated with a higher risk of OSCC than the G allele (OR, 1.501;
      95% CI, 1.026 to 2.196). No difference in rs763780 frequencies was observed. The
      rs2275913 AA and rs2397084 TT genotypes also were associated with late clinical
      stages and poor tumor differentiation. In addition, stratification analysis
      indicated that the rs2275913 AA genotype increased OSCC risk among smoking and
      drinking populations (OR, 4.000; 95% CI, 1.404 to 11.394; and OR, 3.500; 95% CI,
      1.018 to 12.030, respectively). In a smoking population, an rs9382084 T-allele
      carrier has a greater potential risk of OSCC than the overall population (OR,
      2.200; 95% CI, 1.009 to 4.797). CONCLUSIONS: The results of this study suggest a
      significant association of rs2275913 and rs2397084 but not rs763780 with OSCC
      risk, and this was related to tumor stage and differentiation. In addition, the
      IL-17A and IL-17F polymorphisms can interact with smoking and drinking to enhance
      the risk of OSCC developing.

PMID- 25579010
TI  - Facial dysmorphology and odontogenic tumor development associated with inborn
      errors of metabolism: a case report.
AB  - PURPOSE: Inborn errors of metabolism (IEMs) are genetic disorders that alter
      normal physiologic functioning. Deficiency of 3-methylcrotonyl-coenzyme A
      carboxylase is one such IEM that can lead to major episodes of metabolic
      dysfunction. Certain IEMs are associated with characteristic congenital
      dysmorphic facial features. This can be problematic, because these dysmorphisms
      can mask underlying tumor growth. Literature is lacking on a causal relation
      between IEM and odontogenic tumor development. MATERIALS AND METHODS: This case
      was explained in detail and a review of the literature was undertaken. PubMed was
      used to search for articles involving surgical management of odontogenic myxoma
      (OM) and associations between odontogenic tumors and IEM. RESULTS: It was
      determined that the development of odontogenic tumors, specifically OM, is
      associated with IEMs. These tumors can easily be overlooked as a common
      dysmorphic feature of an IEM. CONCLUSION: IEMs lead to major metabolic
      disturbances and, thus, can alter the cellular microenvironment. Hypothetically,
      these alterations can lead to the development of odontogenic tumors. With the
      diagnosis of IEM becoming more common owing to improved newborn screening,
      careful attention should be given to these patients because of the possibility
      that dysmorphologic facial features could be masking underlying tumor growth.

PMID- 25579011
TI  - Delayed treatment of parotid sialocele: a functional approach and review.
AB  - The present report focused on 2 cases treated successfully with a delayed
      minimally invasive surgical approach and reviewed the available studies in which
      this method was used and their outcomes. The current data available suggest that
      the diversion of salivary flow into the oral cavity by cannulation of the distal
      portion of the parotid gland duct from the sialocele into the mouth, through the
      ostium or using a new controlled internal fistula creation, is a reliable,
      relatively simple, and effective procedure. It is available to the clinician when
      delayed treatment is needed, with low complication potential and great
      tolerability. The procedure allows a definite solution to the problem, avoiding
      undesirable outcomes, and preserves parotid gland functionality throughout the
      process of healing.

PMID- 25579012
TI  - From newborn to toddler: report of two cases of congenital granular cell tumor.
AB  - A congenital granular cell tumor (CGCT) is an uncommon benign soft tissue lesion
      that usually arises from the alveolar ridge in newborns. It can severely
      interfere with the respiratory and feeding systems, if left untreated. We present
      the cases of 2 newborn infants with protruded intraoral tumors that severely
      compromised breastfeeding. The tumors were removed by water laser without the
      need for suturing or pain medication. Histopathologic assessment was performed
      for definitive diagnosis, and the children were followed until full primary
      dentition was observed without any sign of CGCT recurrence.

PMID- 25579013
TI  - Fracture healing using degradable magnesium fixation plates and screws.
AB  - PURPOSE: Internal bone fixation devices made with permanent metals are associated
      with numerous long-term complications and may require removal. We hypothesized
      that fixation devices made with degradable magnesium alloys could provide an
      ideal combination of strength and degradation, facilitating fracture fixation and
      healing while eliminating the need for implant removal surgery. MATERIALS AND
      METHODS: Fixation plates and screws were machined from 99.9% pure magnesium and
      compared with titanium devices in a rabbit ulnar fracture model. Magnesium device
      degradation and the effect on fracture healing and bone formation were assessed
      after 4 weeks. Fracture healing with magnesium device fixation was compared with
      that of titanium devices using qualitative histologic analysis and quantitative
      histomorphometry. RESULTS: Micro-computed tomography showed device degradation
      after 4 weeks in vivo. In addition, 2-dimensional micro-computed tomography
      slices and histologic staining showed that magnesium degradation did not inhibit
      fracture healing or bone formation. Histomorphology showed no difference in bone
      bridging fractures fixed with magnesium and titanium devices. Interestingly,
      abundant new bone was formed around magnesium devices, suggesting a connection
      between magnesium degradation and bone formation. CONCLUSION: Our results show
      potential for magnesium fixation devices in a loaded fracture environment.
      Furthermore, these results suggest that magnesium fixation devices may enhance
      fracture healing by encouraging localized new bone formation.

PMID- 25579014
TI  - Challenges in the reconstruction of bilateral maxillectomy defects.
AB  - PURPOSE: Bilateral maxillectomy defects, if not adequately reconstructed, can
      result in grave esthetic and functional problems. The purpose of this study was
      to investigate the outcome of reconstruction of such defects. MATERIALS AND
      METHODS: This is a retrospective case series. The defects were analyzed for their
      components and the flaps used for reconstruction. Outcomes for flap loss and
      functional indices, including oral diet, speech, and dental rehabilitation, also
      were evaluated. RESULTS: Ten consecutive patients who underwent bilateral
      maxillectomy reconstruction received 14 flaps. Six patients had malignancies of
      the maxilla, and 4 patients had nonmalignant indications. Ten bony free flaps
      were used. Four soft tissue flaps were used. The fibula free flap was the most
      common flap used. Three patients had total flap loss. Seven patients were alive
      and available for functional evaluation. Of these, 4 were taking an oral diet
      with altered consistency and 2 were on a regular diet. Speech was intelligible in
      all patients. Only 2 patients opted for dental rehabilitation with removable
      dentures. CONCLUSIONS: Reconstruction after bilateral maxillectomy is essential
      to prevent esthetic and functional problems. Bony reconstruction is ideal. The
      fibula bone free flap is commonly used. The complexity of the defect makes
      reconstruction difficult and the initial success rate of free flaps is low.
      Secondary reconstructions after the initial flap failures were successful. A
      satisfactory functional outcome can be achieved.

PMID- 25579015
TI  - Course of the mandibular incisive canal and its impact on harvesting symphysis
      bone grafts.
AB  - PURPOSE: To characterize the anatomic course of the mandibular incisive canal to
      define parameters for harvesting autogenous bone from the symphysis of the
      mandible. MATERIALS AND METHODS: A series of osteotomies were completed between
      the mental foramina in the anterior mandibles of 19 cadavers. Methylene blue dye
      was used to help identify the incisive canal. From the canal, distances to key
      adjacent landmarks were measured with a Boley gauge to 0.1 mm. Measurements
      included distances from the mandibular incisive canal to the buccal cortex, the
      lingual cortex, the inferior border of the mandible, the apices of the teeth, and
      the buccal cementoenamel junction (CEJ) of the teeth. RESULTS: The canal
      decreased in diameter from lateral to medial. It tended to be closer to the
      buccal cortical bone than to the lingual cortex (P < .001) and was, at times,
      directly abutting the buccal cortex (average distance to buccal cortex, 3.5 mm).
      The canal maintained a relatively constant distance from the apices of the teeth
      (approximately 7 to 8 mm), coursing inferiorly under the longer canines
      bilaterally. The canal became increasingly difficult to identify toward the
      midline, likely dispersing into microscopic tributaries. CONCLUSIONS: The authors
      suggest several modifications to the standard surgical approach to the symphysis
      area during the harvest of bone grafts. When the goal is to avoid the mandibular
      incisive canal, osteotomies should not exceed a depth of 4 mm, should be at least
      5 mm anterior to the mental foramen, and 9 mm below the root apices (or 23 mm
      below the lowest facial CEJ) and should maintain the contour of the mandible's
      inferior border. Alternatively, some degree of canal compromise can be accepted
      and larger grafts can be obtained by increasing the depth of the harvest in the
      horizontal dimension or decreasing the distance from the osteotomy to the root
      apices (or the CEJ) in the vertical dimension.

PMID- 25579016
TI  - Addressing alcohol-related harms within maxillofacial trauma practice.
AB  - PURPOSE: A brief intervention, conducted in the short-term care setting after an
      alcohol-related injury, has been reported to be highly beneficial in reducing the
      risk of reinjury and in reducing the subsequent level of alcohol consumption.
      This project aimed to understand Australasian oral and maxillofacial surgeons'
      attitudes, knowledge, and skills in alcohol screening and brief intervention
      within short-term care settings for patients admitted with facial trauma.
      MATERIALS AND METHODS: A Web-based survey was made available to all members of
      the Australian and New Zealand Association of Oral and Maxillofacial Surgeons
      (200 to 250 members), promoted through a number of e-mail bulletins sent by the
      association to all members. Implied consent was assumed for participants who
      completed the online survey. The survey explored the surgeons' current level of
      involvement in treating patients with alcohol-related facial trauma, as well as
      their knowledge of and attitudes toward alcohol screening and brief intervention.
      The survey also explored their willingness to undergo further training and
      involvement in implementing a screening and brief intervention program. Parts of
      the survey were based on a hypothetical case with facial injury and a drinking
      history that was presented to the participants, and the participants were asked
      to give their response to this scenario. RESULTS: A total of 58 surgeons
      completed the online survey. Of the surgeons surveyed, 91% were men and 88% were
      consultant surgeons. Seventy-one percent would take an alcohol history, 29% would
      deliver a brief alcohol intervention, and 14% would refer the patient to an
      alcohol treatment service or clinician. Forty percent agreed that they had
      adequate training in managing patients with alcohol-related injuries, whereas 17%
      and 19% indicated that they had adequate time and adequate resources,
      respectively. Of the surgeons, 76% reported the need for more information on
      where to refer patients for appropriate alcohol treatment. CONCLUSIONS: The study
      findings confirm the challenges and barriers to implementing a brief alcohol
      intervention in current practice. Service gaps, as well as opportunities for
      training, exist.

PMID- 25579017
TI  - How accurate is the treatment of midfacial fractures by a specific navigation
      system integrating "mirroring" computational planning? Beyond mere average
      difference analysis.
AB  - PURPOSE: To evaluate the accuracy of a specific navigation system integrating
      "mirroring" computational planning in the treatment of midfacial fractures by
      comparing planned with actual postoperative 3-dimensional (3D) images. PATIENTS
      AND METHODS: Preoperative planned and postoperative 3D computed tomographic (CT)
      and cone-beam CT (CBCT) images of 20 patients with midfacial fractures were
      analyzed. Images were fused using dedicated software (iPlan Cranial 2.6). They
      were imported in Standard Tessellation Language (STL) format to open-source
      software (Meshlab) and resized to delineate the surgically repositioned portion
      of bone. The images were imported in STL format to ad hoc software for
      calculating the surface differences between the 2 3D images. The distribution of
      the differences was assessed using boxplots for each patient, and the proportion
      of the actual image close to the planned image was estimated by the proportion of
      values within an accuracy cutoff set at +/-2 mm. RESULTS: The mean difference
      between the 2 3D surfaces was 0.12 mm. The proportion of values between the 2
      surfaces and included within the interval of accuracy was greater than 90% in 6
      patients (30%), 80 to 90% in 6 patients (30%), 50 to 80% in 7 patients (35%), and
      less than 50% in 1 patient (5%). CONCLUSION: This study showed that post
      traumatic midfacial reconstruction can be accurately approximated and thus
      predicted by a specific navigation system integrating "mirroring" computational
      planning for most patients. Further study should examine risk factors for
      inaccurate prediction.

PMID- 25579018
TI  - A 2-year follow-up of changes after bimaxillary surgery in patients with
      mandibular prognathism: 3-dimensional analysis of pharyngeal airway volume and
      hyoid bone position.
AB  - PURPOSE: The aims of this study were to use 3-dimensional cone-beam computed
      tomography (CBCT) to evaluate how the upper airway and hyoid bone position
      changed after orthognathic surgery in patients with skeletal Class III
      malocclusions and to analyze the relations among upper airway changes, the change
      in the position of the hyoid bone, and postsurgical stability. MATERIALS AND
      METHODS: CBCT scans were obtained from 15 patients with mandibular prognathism
      before surgery (T0), 6 months after surgery (T1), 1 year after surgery (T2), and
      2 years after surgery (T3). Positional displacement of the hyoid bone was
      assessed using the coordinates at T0, T1, T2, and T3. In addition, the volume of
      each patient's pharyngeal airway was measured. Differences in CBCT scans at the
      established time points were determined by the Wilcoxon signed rank test. The
      Spearman correlation coefficient was used to determine the relations among
      changes in hyoid bone position, airway volume, and skeletal reference points.
      RESULTS: The hyoid bone moved backward at 6 months after surgery (T0 to T1), and
      the total volume of the pharyngeal airway was considerably decreased at the same
      time points. At 1 year after surgery (T1 to T2), although the hyoid moved more
      posteriorly and the total volume of the pharyngeal airway was decreased, the
      changes were not major. At 2 years after surgery, the hyoid bone moved anteriorly
      and the size of the upper pharyngeal airway was increased (T2 to T3). CONCLUSION:
      The hyoid bone moved posteriorly and the pharyngeal airway volume was decreased
      at 6 months after bimaxillary surgery. These measurements had a tendency to
      recover at 2 years postoperatively. The decrease in pharyngeal airway volume was
      not correlated with positional changes of the hyoid bone.

PMID- 25579019
TI  - Salivary duct carcinoma ex pleomorphic adenoma of the palate: a case report.
AB  - Carcinoma ex pleomorphic adenoma is a rare malignancy of the head and neck,
      particularly in the minor salivary glands. Most cases arise in the major salivary
      glands, most commonly in the parotid gland, followed by the submandibular gland.
      The malignant component of the tumor varies, but can be salivary duct carcinoma,
      adenoid cystic carcinoma, mucoepidermoid carcinoma, squamous cell carcinoma, or
      adenocarcinoma, not otherwise specified. Primary salivary duct carcinoma is also
      a rare malignancy of the head and neck. Similar to carcinoma ex pleomorphic
      adenoma, it is more common in the major salivary glands, with the parotid gland
      accounting for 88% and the submandibular gland for 10% of cases. To date, only 25
      known cases of primary salivary duct carcinoma arising in the minor salivary
      glands have been documented, with most arising in the palate. Salivary duct
      carcinoma ex pleomorphic adenoma of the minor salivary glands appears to be even
      rarer. Our case of salivary duct carcinoma ex pleomorphic adenoma of the palate
      is the first complete report, to our knowledge, in the English-language
      scientific literature. 

PMID- 25579020
TI  - An atypical metastasis of renal clear cell carcinoma to the upper lip: a case
      report.
AB  - Metastatic lesions of the oral cavity are extremely rare, accounting for
      approximately 1% of all malignant oral tumors. Renal clear cell carcinoma (RCCC)
      constitutes about 3% of the solid tumors in adults. It is the third most frequent
      neoplasm to metastasize to the head and neck region, preceded by breast and lung
      carcinoma. Because of the silent growth of this neoplasm, most patients are
      asymptomatic and are diagnosed in an advanced stage, frequently with metastases.
      We report an unusual case of a 60-year-old male patient with an ulcerated nodule
      on the upper lip mimicking a keratoacanthoma. He was treated for left-sided RCCC
      5 months earlier. The lesion was excised, and the histopathologic findings were
      suggestive of metastatic RCCC. The clinical features, prognosis, and treatment
      modalities for metastatic lesions are reviewed in our report. This case is a
      rarity because only 3 cases of metastatic RCCC of the upper lip have been
      reported in the literature. 

PMID- 25579021
TI  - Helminth species richness of introduced and native grey mullets (Teleostei:
      Mugilidae).
AB  - Quantitative complex analyses of parasite communities of invaders across
      different native and introduced populations are largely lacking. The present
      study provides a comparative analysis of species richness of helminth parasites
      in native and invasive populations of grey mullets. The local species richness
      differed between regions and host species, but did not differ when compared with
      invasive and native hosts. The size of parasite assemblages of endohelminths was
      higher in the Mediterranean and Azov-Black Seas, while monogeneans were the most
      diverse in the Sea of Japan. The helminth diversity was apparently higher in the
      introduced population of Liza haematocheilus than that in their native habitat,
      but this trend could not be confirmed when the size of geographic range and
      sampling efforts were controlled for. The parasite species richness at the
      infracommunity level of the invasive host population is significantly lower
      compared with that of the native host populations that lends support to the enemy
      release hypothesis. A distribution pattern of the infracommunity richness of
      acquired parasites by the invasive host can be characterized as aggregated and it
      is random in native host populations. Heterogeneity in the host susceptibility
      and vulnerability to acquired helminth species was assumed to be a reason of the
      aggregation of species numbers in the population of the invasive host. 

PMID- 25579022
TI  - [Inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline on myofibroblast
      differentiation of MRC-5 human fetal lung fibroblasts inuced by Ang II].
AB  - OBJECTIVE: To explore the inhibition effect of N-acetyl-seryl-aspartyl-lysyl
      proline (Ac-SDKP) on myofibroblast differentiation of MRC-5 human fetal lung
      fibroblasts induced by angiotensin (Ang) II. METHODS: The study was divided into
      2 step: (1) MRC-5 human fetal lung fibroblasts was induced for 48 h at different
      dose of Ang II and at different time point by 100 nmol/L Ang II. Then the
      expression of collagen type I and alpha-smooth muscle actin (alpha-SMA) were
      mesaured by western blot. (2) MRC-5 human fetal lung fibroblasts were divided
      into 4 group: (1) control, (2) Ang II, (3) Ang II+Ac-SDKP, (4) Ang II+8-Me-cAMP
      (a specific activator of Epac). The alpha-SMA expression was observed by
      immnocytochemical stain. The protein expression of collagen type I, alpha-SMA,
      serum response factor (SRF), myocardin-related transcription factor (MRTF)-A,
      exchange protein directly activated by cAMP (Epac) 1, 2 were measured by Westen
      blot. RESULTS: Myofibroblast differentiation could be induced by Ang II from MRC
      5 cells with a dose- and time-dependent manner. The up-regulation of SRF and MRTF
      A were observed in MRC-5 cells induced by Ang II and accompanied with collagen I
      and alpha-SMA increased. Pre-treatment with 8-Me-cAMP or Ac-SDKP could attenuated
      all this changes induced by Ang II, and promoted the expression of Epac1.
      CONCLUSION: Ac-SDKP can inhibit the myofibroblast differentiation of MRC-5 cells
      induced by Ang II via Epac1 activating.

PMID- 25579023
TI  - [Effect of thalidomide in a mouse model of paraquat-induced acute lung injury and
      the underlying mechanisms].
AB  - OBJECTIVE: To investigate the effects of thalidomide in a mouse model of paraquat
      induced acute lung injury and the mechanisms underlying the properties of
      thalidomide. METHODS: Male ICR mice were randomly allocated into four groups:
      nomal control group (n = 30), thalidomide control group (n = 30), paraquat
      poisioning group (n = 30) and thalidomide treatment group (n = 90). Mice were
      sacrificed at 1d, 3d and 7d after paraquat poisioning. The level of (MDA)
      malondialdehyde, Superoxidedi-smutase (SOD) and glutathione (GSH) in the lung
      tissue were measuerd by chemical colorimetry. The expression of Nrf2 mRNA was
      determined by RT-PCR; Nuclear protein Nrf2 was abserved by Western blotting;
      Pathological changes of lung tissue were observed under light microscope by HE
      stain; the lung apoptosis cells were detected by TUNEL. RESULTS: The levels of
      MDA, SOD and the expressions Nrf2 mRNA and protein Nrf2 in lung tissue were all
      markedly increased in mice of paraquat poisioning group than those in nomal group
      at 1 d, 3 d, 7 d. In contrast, the levels of GSH were decreaseel (P<0.05).
      Compared with paraquat poisioning group, the pulmonary SOD, Nrf2 mRNA and protein
      were increased and the lung wet dry ratio were all significantly decreased in
      mice of THD treatment group at 1 d, 3 d, 7 d (P<0.05). THD alleviated the
      pulmonary damage in the lightmicroscope at 3d after paraquat poisioning. The
      apoptosis index was markedly decreased in THD treatment groups comparing to
      paraquat piosioning group (P<0.05). CONCLUSIONS: Lipid peroxide damage was one of
      the mechanisms of paraquat poisioning, thalidomide could attenuate paraquat
      induced acute lung injury and its mechanism may be activating the Nrf2-ARE
      signaling pathway to protect mouse from Lipid peroxide damage.

PMID- 25579024
TI  - [Dynamic changes of a group of cytokines in phosgene-induced lung injury and the
      function of ulinastatin].
AB  - OBJECTIVE: To investigate the dynamic changes of a group of cytokines in phosgene
      induced lung injury and the function of different dose of ulinastatin through
      animal experiment. METHODS: 104 male SD rats were randomly assigned into the
      control group, ulinastatin control group, phosgene treatment groups and different
      dose of ulinastatin intervention groups, 8 rats each group. Treatment groups were
      dynamic constant exposure in phosgene, and immediately injected ulinastatin
      intraperitoneal, and then the experimental animal, the lung tissue biopsy, lung
      wet/dry ratio, RT-PCR detection, the plasma for detection of Bio-Plex 18
      cytokines. RESULTS: Compared with the control group, plasma concentrations of IL
      1alpha, IL-6, GM-CSF, TNF-alpha, INF-gamma, MIP-3alpha, VEGF were increased
      significantly first (2 h), and gradually decreased with the passage of time , the
      difference was statistically significant (P < 0.05). Plasma concentrations of IL
      4, IL-10 were decreased earlier (2h, 6 h) and increased later (24 h) (P < 0.05).
      The change of plasma concentration of IL-13 was not obvious earlier (2 h) and
      still rising later (24h), the difference was statistically significant (P <
      0.05). After drug intervention, the levels of pro-inflammatory cytokines declined
      and the levels of anti-inflammatory cytokines raise by different degrees at
      different times in ulinastatin intervention groups, the difference was
      statistically significant. The degree of lung injury was improved than the
      phosgene treatment groups and better in high dose of ulinastatin intervention
      group. The expression of IL-10, IL-4, IL-13-mRNA of tissue increased in
      accordance with plasma results. CONCLUSION: A group of cytokines are dynamicly
      changed in phosgene-induced lung injury by time. High dose of ulinastatin can
      improved phosgene-induced lung injury, regulate the synthesis and release of
      inflammatory cytokines and inhibit inflammatory react in a dose-dependent manner.

PMID- 25579025
TI  - [Effects of lead exposure on copper and copper transporters in choroid plexus of
      rats].
AB  - OBJECTIVE: To investigate the effects of lead exposure on the copper
      concentration in the brain and serum and the expression of copper transporters in
      the choroid plexus among rats. METHODS: Sixty specific pathogen-free Sprague
      Dawley rats were randomly divided into a control group and three lead-exposed
      groups, with 8 mice in each group. The lead-exposed groups were orally
      administrated with 500 (low-dose group)), 1 000 (middle-dose group), and 2 000
      mg/L (high-dose group) lead acetate in drinking water for eight weeks. And the
      rats in control group were given 2 000 mg/L sodium acetate in drinking water. The
      content of lead and copper in the serum, hippocampus, cortex, choroid plexus,
      bones, and cerebrospinal fluid (CSF) was determined by inductively coupled plasma
      mass spectrometry (ICP-MS). Confocal and real-time PCR methods were applied to
      measure the expression of copper transporters including copper transporter 1
      (Ctr1), antioxidant protein 1 (ATX1), and Cu ATPase (ATP7A). RESULTS: Compared
      with the control group, the lead-exposed groups showed significantly higher lead
      concentrations in the serum, cortex, hippocampus, choroid plexus, CSF, and bones
      (P < 0.05) and significantly higher copper concentrations in the CSF, choroid
      plexus, serum, and hippocampus (P < 0.05). Confocal images showed that Ctr1
      protein was expressed in the cytoplasm and cell membrane of choroid plexus in
      control group. However, Ctr1 migrated to CSF surface microvilli after lead
      exposure. Ctr1 fluorescence intensity gradually increased with increasing dose of
      lead, except that the middle-dose group had a higher Ctr1 fluorescence intensity
      than the high-dose group. In addition, the middle- and high-dose groups showed a
      lower ATX1 fluorescence intensity compared with the control group. Real-time PCR
      data indicated that the three lead-exposed groups showed significantly higher
      mRNA levels of Ctr1 and ATP7A compared with the control group (P < 0.05).
      CONCLUSION: Copper homeostasis in the choroid plexus is affected by lead exposure
      to induce copper homeostasis disorders in brain tissue, which may be one of the
      mechanisms of lead neurotoxicity.

PMID- 25579026
TI  - [Welders' siderosis: a retrospective cohort study on welder's pneumoconiosis
      patients with small round opacities on chest radiograph].
AB  - OBJECTIVE: To study the radiographycal changes and prognosis of welders'
      pneumoconiosis patients diagnosed within the last few years. METHODS:
      Occupational hygienics data (including years on welding work, welding materials
      exposed to and work environment), symptoms, lung function test results and follow
      up data of 136 welders' pneumoconiosis patients were collected retrospectively.
      The follow-up lasted up till June 30, 2014, with follow-up interval being one
      year. Chest radiographs were read/reviewed together by 3 senior experts
      experienced in pneumoconiosis diagnosing and shape and size of small opacity,
      overall profusion, affected lung zones and pneumoconiosis stages were all logged.
      RESULTS: Of all 136 pneumoconiosis cases, five were of stage II and 131 were
      stage I, and they had been engaged in welding work for 9.2+/-6.34 years. All
      patients were present with slight symptoms including coughing, chest distress and
      dyspnea, while their lung function remained normal. Small round opacities were
      found on chest radiographs of 88.9% of the 136 cases. Years of follow-up on 131
      cases of stage I Welder's pneumoconiosis showed that irregular small opacities
      remained fundamentally unchanged, while small round opacities tended to gradually
      lessen instead of coalescence. Two years after primary diagnosing, the total
      affected lung zones of follow-up objects were noticed to start lessening, and
      reduced by 0.02 per patient among the 48 follow-up subjects. Of the 48 cases
      followed up up to six years after primary diagnosing, the affected lung zone
      number was reduced by 0.54 per patient while 4 cases (8%) went down to below
      stage I. As of the 36 patients followed up 10 years after after primary
      diagnosis, the number of affected lung areas decreased by 1.14, and 22% (8 cases)
      appeared less than stage I on chest radiograph. CONCLUSION: It seemed that the so
      called welders' pneumoconiosis featuring small round opacities tended to get
      improved over time, which suggested the diagnosis of siderosis.

PMID- 25579027
TI  - [Characteristics analysis on acute occupational poisoning accident from 2006 to
      2013 in Jiangsu Province].
AB  - OBJECTIVE: To analyze the characteristics of acute occupational poisoning
      accidents reported in Jiangsu Province between 2006 to 2013. METHODS: Based on
      the reported data of occupational diseases, we analysis indicators such as type,
      gender, age, and enterprise size of acute occupational poisoning. RESULTS: (1)
      There were 226 acute occupational poisoning accidents for 8 years with 436
      workers poisoned and 13 died. The Poisoning mortality rate was 2.98%. (2) The
      accidents occurred more frequently from March to August each year. (3)
      Asphyxiating gases, irritant gases and organic solvents are the main chemicals
      which caused these poisoning accidents. (4) Most of the cases come from the
      chemical industry and light industry . They more occurred in men and presented
      the trend of aging. (5) Most of them are from the south of Jiangsu and coastal
      areas. New cases of acute occupational poisoning mainly concentrated in small
      businesses. CONCLUSION: Strengthening the supervision on high incidence area and
      high-risk industry is the key point to reduce the incidence of acute occupational
      poisoning accident.

PMID- 25579028
TI  - [Analysis of newly diagnosed occupational diseases in Wuxi City 2006 to 2013].

PMID- 25579029
TI  - [A study of GM (1, 1) model for predicting the incidence trends of pneumoconiosis
      cases of an area].
AB  - OBJECTIVE: To explore the application of the gray series model GM (1, 1) in
      predicting trends in the incidence of pneumoconiosis and evaluate its degree of
      predicted precision. METHODS: Analyzing the incidence of pneumoconiosis in this
      region from 2009 to 2013, and predicting the incidence of pneumoconiosis of the
      area in 2014-2016 by establishing GM (1, 1) according to the gray system theory.
      RESULTS: Using occupational pneumoconiosis population data from 2009 to 2013, to
      establish GM (1, 1) model: yt = 1396.89e(0.12(t-1)), alpha = -0.12, u = 147.2.
      The pneumoconiosis in 2014, 2015, 2016 were predicted respectively 51, 47, 43
      cases based on the GM (1, 1) model, and C value of model is 0.15, P value is 1,
      all of them meet the requirements of model predictions. It shows the cases of
      pneumoconiosis are rising significantly. CONCLUSION: GM (1, 1) model can be used
      to predict the recent trend in the incidence of pneumoconiosis.

PMID- 25579030
TI  - [Occupational hestth status a power supply enterprise in eastern China].

PMID- 25579031
TI  - [The investigation of exercise-induced fatigue on pesticide spraying operation].
AB  - OBJECTIVE: To evaluate the exercise-induced fatigue in operators during pesticide
      spraying based on surface electromyography (sEMC) signals and heart rate.
      METHODS: The sEMG signals were recorded from the right trapezius, biceps brachii,
      extensor digitorum, and flexor digitorum of 19 operators by portable
      electromyography units during pesticide spraying using 3WS-16 manual sprayers.
      Meanwhile, the heart rate of operators was measured by the ambulatory blood
      pressure monitoring system. The changes in median frequency and heart rate were
      analyzed. RESULTS: Pesticide spraying was defined as low-intensity labor. The
      median frequency of the right trapezius, biceps brachii, extensor digitorum, and
      flexor digitorum decreased significantly as pesticide spraying went on (P <
      0.05). The body remained in a state of slight fatigue from 8 min after pesticide
      spraying began to the end of the operation. CONCLUSION: The degree of exercise
      induced fatigue of operators can be evaluated based on sEMG signals and heart
      rate during pesticide spraying.

PMID- 25579032
TI  - [Exploration of biological limitvalue for occupational exposure to ethyllenzeve].

PMID- 25579033
TI  - [Effects of carbon disulfide inhalation on lipid levels of ApoE gene knockout
      mice and C57BL/6J mice].
AB  - OBJECTIVE: To investigate the effects of carbon disulfide (CS(2)) inhalation on
      the lipid levels of ApoE knockout gene mice and C57BL/6J mice. METHODS: Fifty-one
      male ApoE gene knockout mice were randomly divided into four groups: CS(2)
      exposed normal diet group, CS(2)-unexposed normal diet group, CS(2)-exposed high
      fat diet group, and CS(2)-unexposed high-fat diet group. Fifty male C57BL/6J mice
      were divided into four groups in the same way. The exposed groups received 1000
      mg/m3 CS(2) by static inhalation (5h/d, 5d/w) for four weeks. The weight of each
      mouse was determined and recorded once a week. On the 14th day of exposure, six
      mice in each group were randomly selected to measure serum total cholesterol (TC)
      levels. On the 28th day of exposure, the serum levels of TC and low-density
      lipoprotein (LDL) in the remaining mice were measured. RESULTS: The mean weight
      gain of exposed groups was less than that of the unexposed groups. On the 14th
      and 28th days of experiment, the TC levels of the CS2-exposed high-fat diet group
      were significantly higher than those of the CS(2)-unexposed high-fat diet group
      among ApoE knockout gene mice (P < 0.01 for both). On the 14th day of experiment,
      the TC levels of the CS(2)-unexposed high-fat diet group were significantly
      higher than those of the CS(2)-unexposed normal-diet group among C57BL/6J mice
      group (P < 0.05). On the 28th day of experiment, the LDL levels of the CS(2)
      exposed high-fat diet group were significantly higher than those of the CS(2)
      unexposed high-fat diet group among ApoE knockout gene mice (P = 0.003).
      CONCLUSION: CS(2) exposure, high-fat diet, and ApoE gene knockout can elevate
      blood lipids in mice, thus increasing the risk of atherosclerosis.

PMID- 25579034
TI  - [To observe the right heart function of silicosis with cor pulmonale by
      noninvasive double level positive airway pressure treatment].

PMID- 25579035
TI  - [Pulmonary rehabilitation therapy of pneumoconiosis patients].

PMID- 25579036
TI  - [Nursing of treating silicosis with pneumothorax by in dwelling chest
      catheterization with needle].

PMID- 25579037
TI  - [Accidental oral intake of potassiumpermanganate-induced acute lung injury
      combined pneumomediastinum: a case report].

PMID- 25579038
TI  - [One caes of acute poisoning neurological disease and allergic dermatitis with
      hydrazine hydrate].

PMID- 25579039
TI  - [Analysis on cases of acute dimethyl oxalate poisoning].

PMID- 25579040
TI  - [A case of multiple organ damage induced by chronic cresol intoxication: a case
      report].

PMID- 25579041
TI  - [The clinical analysis of treatment of hemoperfusion combined Xuebijing for
      paraqut poisoning].

PMID- 25579042
TI  - [Milk gargle and activated carbon retention enema in the application of the
      treatment of acute paraquat poisoning].

PMID- 25579043
TI  - [Comparative study of different methods of blood purification treatment of
      paraquat intoxication].
AB  - OBJECTIVE: To investigate the different effect of three methods of blood
      purification for paraquat poisoning patients:hemoperfusion (HP), hemoperfusion
      combined with hemodialysis (HP + HD), hemoperfusion combined with continuous veno
      venous hemofiltration (HP + CVVH). METHODS: 72 cases of paraquat poisoning
      patients were divided into three groups after giving conventional therapy HP
      group, HP + HD group, HP + CVVH group. Compared the rate of decline
      concentrations of paraquat in blood, the liver and the kidney damage between
      before and after blood purification and contrast the mortality in three groups
      after different method of blood purification. RESULTS: The rate of decline
      concentrations of paraquat in blood of the HP + HD group and HP + CVVH group were
      both significantly greater than the HP group, but this result of HP + HD group
      has no significant difference compared with HP + CVVH group; Among the three
      groups of patients after 72 hours, the degree of dysfunction of liver of the HP +
      HD group and HP + CVVH group were both significantly lower than the HP group,
      whilely the degree of dysfunction of kidney of the HP + HD group was
      significantly lower than the HP group and the HP + CVVH group. The survival time
      of the HP + HD group and the HP + CVVH group were significant linger than the HP
      group, but the comparison among the three groups had no significant difference in
      mortality. CONCLUSION: Three blood purification methods can effectively remove
      paraquat absorbed into the blood, and the hemoperfusion combined with
      hemodialysis or continuous veno-venous hemofiltration can effectively reduce the
      degree of damage of liver and kidney and also can prolong survival time, but did
      not significantly improve the survival rate of patients.

PMID- 25579044
TI  - [Progress in the mechanism of cytokine on lung injury caused by acute paraquat
      poisoning].

PMID- 25579045
TI  - [The review of study on glyphosate hebicide toxic effects].

PMID- 25579047
TI  - [Detoxification drug treatment of thalliccm poisoning].

PMID- 25579046
TI  - [Research progress of hard metal lung disease diagnosis and treatment].

PMID- 25579048
TI  - [Advances in the roles of cytochrome P450 2E1 in the pathogenesis of alcoholic
      fatty liver].

PMID- 25579049
TI  - Mild Cognitive Impairment in Rural Tanzania: Prevalence, Profile, and Outcomes at
      4-Year Follow-up.
AB  - OBJECTIVE: Mild cognitive impairment (MCI) is recognized as a high-risk condition
      for conversion to dementia, although data on outcomes of MCI in sub-Saharan
      Africa are scarce. We investigated outcomes of MCI over a 4-year period in
      Tanzania and considered risk factors for conversion to dementia. METHODS: In a
      longitudinal cohort study in the Hai district, Tanzania, patients with MCI were
      identified during a two-phase prevalence study carried out in 2010. Of 1,198
      people aged 70 years and over screened in phase I, a stratified sample of 296
      were fully assessed in phase II. MCI was defined according to international
      consensus criteria. DSM-IV criteria were used for dementia diagnosis. Background
      demographic and risk factor data were collected, and neuropsychiatric symptoms
      were assessed using the neuropsychiatric inventory. Patients were followed-up in
      2011, 2012 and 2014. RESULTS: Forty-six MCI patients were identified. After
      adjusting for stratification, the crude prevalence of MCI was 7.0% (95% CI: 3.6
      10.4). Over a 4-year period, 15 patients (32.6%) progressed to dementia, 2
      patients (4.3%) returned to normal cognition, 1 developed late-onset
      schizophrenia, 8 patients (17.4%) had stable MCI, 19 patients (41.3%) died, and 1
      refused assessment. Age, sex, education levels, body mass index, hypertension,
      and comorbidity were not associated with progression to dementia. CONCLUSION: In
      this rural Tanzanian population, rates of conversion from MCI to DSM-IV dementia
      were similar to those reported in high-income countries. Over a third of all
      patients had died at the 4-year follow-up.

PMID- 25579051
TI  - Light evoked potentials measured by electroretinogram may tap into the
      neurodevelopmental roots of schizophrenia.

PMID- 25579050
TI  - Evidence for schizophrenia susceptibility alleles in the Indian population: An
      association of neurodevelopmental genes in case-control and familial samples.
AB  - Schizophrenia is a severe psychiatric disorder with lifetime prevalence of ~1%
      worldwide. A genotyping study was conducted using a custom panel of Illumina 1536
      SNPs in 840 schizophrenia cases and 876 controls (351 patients and 385 controls
      from North India; and 436 patients, 401 controls and 143 familial samples with 53
      probands containing 37 complete and 16 incomplete trios from South India). Meta
      analysis of this population of Indo-European and Dravidian ancestry identified
      three strongly associated variants with schizophrenia: STT3A (rs548181,
      p=1.47*10(-5)), NRG1 (rs17603876, p=8.66*10(-5)) and GRM7 (rs3864075, p=4.06*10(
      3)). Finally, a meta-analysis was conducted comparing our data with data from the
      Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ) that
      supported rs548181 (p=1.39*10(-7)). In addition, combined analysis of sporadic
      case-control association and a transmission disequilibrium test in familial
      samples from South Indian population identified three associations: rs1062613
      (p=3.12*10(-3)), a functional promoter variant of HTR3A; rs6710782 (p=3.50*10(
      3)), an intronic variant of ERBB4; and rs891903 (p=1.05*10(-2)), an intronic
      variant of EBF1. The results support the risk variants observed in the earlier
      published work and suggest a potential role of neurodevelopmental genes in the
      schizophrenia pathogenesis. 

PMID- 25579052
TI  - Cognition and the prediction of functioning in patients with a first treated
      episode of psychosis: a prospective study.
AB  - Past research on the role of cognitive performance in predicting later
      psychosocial functioning for individuals with first treated episode of a
      psychotic disorder has yielded inconsistent results. Several factors have been
      suggested as determining the strength of any such relationship including the type
      of functioning measured, time of the cognitive assessment, covariates included
      and the use of global versus specific measures of cognitive functioning. In the
      current study, we examined the importance of these factors in a five year
      prospective study of individuals with first episode psychotic disorders. Just
      over 80% of the sample had a schizophrenia spectrum disorder. Cognitive
      assessments were carried out after initiation of treatment on 113 patients, and
      at one year for 79 patients. There was evidence that cognition predicted
      occupational functioning and use of a disability pension, but not a summary index
      of functioning or use of supervised housing, at follow-up. Overall I.Q. was a
      more consistent predictor than measures of specific cognitive functions, and
      there was evidence that cognition assessed after presentation for treatment,
      particularly after a year of treatment, was more predictive of later functioning
      than premorbid I.Q. Cognitive functioning, however, did not add to the prediction
      of outcomes beyond the level possible using past educational achievement or
      academic premorbid adjustment. 

PMID- 25579053
TI  - Defining therapeutic benefit for people with schizophrenia: focus on negative
      symptoms.
AB  - Schizophrenia is a complex, heterogeneous, multidimensional disorder within which
      negative symptoms are a significant and disabling feature. Whilst there is no
      established treatment for these symptoms, some pharmacological and psychosocial
      interventions have shown promise and this is an active area of research. Despite
      the effort to identify effective interventions, as yet there is no broadly
      accepted definition of therapeutic success. This article reviews concepts of
      clinical relevance and reports on a consensus conference whose goal was to apply
      these concepts to the treatment of negative symptoms. A number of key issues were
      identified and discussed including: assessment of specific negative symptom
      domains; defining response and remission for negative symptoms; assessment of
      functional outcomes; measurement of outcomes within clinical trials; and the
      assessment of duration/persistence of a response. The group reached a definition
      of therapeutic success using an achieved threshold of function that persisted
      over time. Recommendations were agreed upon with respect to: assessment of
      negative symptom domains of apathy-avolition and deficit of expression symptoms;
      thresholds for response and remission of negative symptoms based on level of
      symptomatology; assessing multiple domains of function including social
      occupation, activities of daily living, and socialization; the need for clinical
      trial data to include rate of change over time and converging sources of
      evidence; use of clinician, patient and caregiver perspectives to assess success;
      and the need for establishing criteria for the persistence of therapeutic
      benefit. A consensus statement and associated research criteria are offered as an
      initial step towards developing broad agreement regarding outcomes of negative
      symptoms treatment. 

PMID- 25579054
TI  - The effects of a single dose of oxytocin on working memory in schizophrenia.

PMID- 25579055
TI  - Perceived emotional intelligence is impaired and associated with poor community
      functioning in schizophrenia and bipolar disorder.
AB  - Schizophrenia and bipolar disorder have been associated with shared and distinct
      emotion processing abnormalities. Initial findings indicate that these disorders
      differ with respect to the domain of emotional intelligence (EI). Individuals
      with schizophrenia display deficits on performance measures of EI, whereas those
      with bipolar disorder do not. However, no research has examined patients'
      subjective beliefs about their own EI (referred to as "perceived EI"). This study
      examined perceived EI, assessed with the Trait Meta-Mood Scale (TMMS), and its
      clinical and functional correlates in outpatients with schizophrenia (n=35) or
      bipolar disorder I (n=38) and matched healthy controls (n=35). The TMMS includes
      three subscales that assess beliefs about one's ability to attend to (Attention
      to Feelings), understand (Clarity of Feelings), and repair emotions (Mood
      Repair). Participants in the clinical groups also completed community functioning
      and symptom assessments. Both clinical groups reported significantly lower
      perceived EI than controls, but did not differ from each other. Higher total TMMS
      correlated with higher levels of independent living in the schizophrenia group
      (r=.36) and better social functioning in the bipolar group (r=.61). In addition,
      although higher Attention to Feelings scores correlated with greater psychiatric
      symptoms in the schizophrenia group, higher scores across all subscales
      correlated with less manic symptoms in the bipolar group. The findings suggest
      that perceived EI is impaired and related to community functioning in both
      disorders. 

PMID- 25579057
TI  - Are caveolae a cellular entry route for non-viral therapeutic delivery systems?
AB  - The development of novel therapies increasingly relies on sophisticated delivery
      systems that allow the drug or gene expression-modifying agent of interest entry
      into cells. These systems can promote cellular targeting and/or entry, and they
      vary in size, charge, and functional group chemistry. Their optimization requires
      an in depth knowledge of the cellular routes of entry in normal and pathological
      states. Caveolae are plasma membrane invaginations that have the potential to
      undergo endocytosis. We critically review the literature exploring whether drug
      or nucleic acid delivery systems exploit and/or promote cellular entry via
      caveolae. A vast majority of studies employ pharmacological tools, co
      localization experiments and very few make use of molecular tools. We provide
      clarification on how results of such studies should be interpreted and make
      suggestions for future studies. 

PMID- 25579058
TI  - Toward a full understanding of the EPR effect in primary and metastatic tumors as
      well as issues related to its heterogeneity.
AB  - The enhanced permeability and retention (EPR) effect of solid tumors as seen with
      nanomedicines and macromolecular drugs is well known. However, many researchers
      appear to lack a full understanding of this effect. The effect varies depending
      on a patient's pathological and physiological characteristics and clinical
      condition. When a patient's systolic blood pressure is low side of about 90mmHg
      instead of 120-130mmHg, the hydrodynamic force pushing blood from the luminal
      side of a vessel into tumor tissue becomes significantly low, which results in a
      low EPR. Also, a vascular embolism in a tumor may impede blood flow and the EPR.
      Here, I describe the background of the EPR effect, heterogeneity of this effect,
      physiological and pathological factors affecting the effect, the EPR effect in
      metastatic tumors, artifacts of the EPR effect with micellar and liposomal drugs,
      problems of macromolecular drug stability and drug release, and access to target
      sites. 

PMID- 25579056
TI  - Inflammatory Chemokines MIP-1delta and MIP-3alpha Are Involved in the Migration
      of Multipotent Mesenchymal Stromal Cells Induced by Hepatoma Cells.
AB  - In vivo, bone marrow-derived multipotent mesenchymal stromal cells (MSC) have
      been identified at sites of tumors, suggesting that specific signals mobilize and
      activate MSC to migrate to areas surrounding tumors. The signals and migratory
      mechanisms that guide MSC are not well understood. Here, we investigated the
      migration of human MSC induced by conditioned medium of Huh-7 hepatoma cells (Huh
      7 CM). Using a transwell migration system, we showed that human MSC migration was
      increased in the presence of Huh-7 CM. Using a human cytokine antibody array, we
      detected increased levels of MIP-1delta and MIP-3alpha in Huh-7 CM. Recombinant
      chemokines MIP-1delta and MIP-3alpha induced MSC migration. Anti-MIP-1delta and
      anti-MIP-3alpha antibodies added to Huh-7 CM decreased MSC migration, further
      suggesting that MIP-1delta and MIP-3alpha were implicated in the Huh-7 CM-induced
      MSC migration. By real-time polymerase chain reaction, we observed an absence of
      chemokine receptors CCR2 and CXCR2 and low expression of CCR1, CCR5, and CCR6 in
      MSC. Expression of these chemokine receptors was not regulated by Huh-7 CM.
      Furthermore, matrix metalloproteinase 1 (MMP-1) expression was strongly increased
      in MSC after incubation with Huh-7 CM, suggesting that MSC migration depends on
      MMP-1 activity. The signaling pathway MAPK/ERK was activated by Huh-7 CM but its
      inhibition by PD98059 did not impair Huh-7 CM-induced MSC migration. Further,
      long-term incubation of MSC with MIP-1delta increased alpha-smooth muscle actin
      expression, suggesting its implication in the Huh-7 CM-induced evolvement of MSC
      into myofibroblasts. In conclusion, we report that two inflammatory cytokines,
      MIP-1delta and MIP-3alpha, are able to increase MSC migration in vitro. These
      cytokines might be responsible for migration and evolvement of MSC into
      myofibroblasts around tumors. 

PMID- 25579062
TI  - Enhancement of vascular endothelial growth factor release in long-term drug
      treated breast cancer via transient receptor potential channel 5-Ca(2+)-hypoxia
      inducible factor 1alpha pathway.
AB  - Chemotherapy targeting anti-angiogenesis in tumors may have insufficient
      efficacy, but little is known about the underlying mechanisms. Here, we showed
      that the Ca(2+)-permeable channel, TrpC5, is highly expressed in human breast
      cancer after long-term chemotherapy drug-treatment. It mediates downstream
      hypoxia-inducible factor 1alpha accumulation in the nucleus, and then activates
      the transcription of vascular endothelial growth factor which promotes tumor
      angiogenesis, leading to a poor chemotherapeutic outcome. We verified this
      mechanism at both the cellular and xenograft levels. Moreover, in samples from
      patients, high TrpC5 expression was correlated with enhanced tumor vasculature
      after chemotherapy. Taken together, our research demonstrated the essential role
      of TrpC5 in tumor angiogenesis when facing the challenge of chemotherapy and
      presents a new potential target for overcoming the high vasculature of human
      breast cancer after chemotherapy. 

PMID- 25579063
TI  - Cu(NO3)2.3H2O-mediated cyanation of aryl iodides and bromides using DMF as a
      single surrogate of cyanide.
AB  - Aryl nitriles were prepared through Cu(NO3)2.3H2O-mediated cyanation of aryl
      iodides and bromides using DMF as a single surrogate of cyanide. Moreover, this
      protocol could be scalable and practiced with benign operation. 

PMID- 25579059
TI  - Radiographic volume analysis as a novel tool to determine nasopalatine duct cyst
      dimensions and its association with presenting symptoms and postoperative
      complications.
AB  - OBJECTIVES: The aims of the study were to use cone beam computed tomography
      (CBCT) images of nasopalatine duct cysts (NPDC) and to calculate the diameter,
      surface area, and 3D-volume using a custom-made software program. Furthermore,
      any associations of dimensions of NPDC with age, gender, presence/absence of
      maxillary incisors/canines (MI/MC), endodontic treatment of MI/MC, presenting
      symptoms, and postoperative complications were evaluated. MATERIAL AND METHODS:
      The study comprised 40 patients with a histopathologically confirmed NPDC. On
      preoperative CBCT scans, curves delineating the cystic borders were drawn in all
      planes and the widest diameter (in millimeter), surface area (in square
      millimeter), and volume (in cubic millimeter) were calculated. RESULTS: The
      overall mean cyst diameter was 15 mm (range 7-47 mm), the mean cyst surface area
      566 mm(2) (84-4,516 mm(2)), and the mean cyst volume 1,735 mm(3) (65-25,350
      mm(3)). For 22 randomly allocated cases, a second measurement resulted in a mean
      absolute aberration of +/-4.2 % for the volume, +/-2.8 % for the surface, and +/
      4.9 % for the diameter. A statistically significant association was found for the
      CBCT determined cyst measurements and the need for preoperative endodontic
      treatment to MI/MC and for postoperative complications. CONCLUSION: In the hands
      of a single experienced operator, the novel software exhibited high repeatability
      for measurements of cyst dimensions. Further studies are needed to assess the
      application of this tool for dimensional analysis of different jaw cysts and
      lesions including treatment planning. CLINICAL RELEVANCE: Accurate radiographic
      information of the bone volume lost (osteolysis) due to expansion of a cystic
      lesion in three dimensions could help in personalized treatment planning.

PMID- 25579064
TI  - Insect motor control: methodological advances, descending control and inter-leg
      coordination on the move.
AB  - Modern approaches, including high performance video, neurophysiology, and
      neurogenetics, allow to analyze invertebrate behavior on all levels of generation
      and performance in an unprecedented way. They allow observation and
      classification of behavior in controlled conditions, dissection of behavioral
      sequencing, identification of levels of processing and locations of associated
      sub-networks and, finally, identification of neuronal components and topologies
      contributing to specific aspects of behaviors. Recently conceptual and
      methodological progress has contributed to unraveling the neural structures
      underlying descending control of insect behavior as well as the mechanisms in
      charge of generating coordinated locomotor movements of the invertebrate
      extremities during walking. This brief review summarizes some of the most
      exciting new findings in these areas of research from the past years. 

PMID- 25579065
TI  - Comments on the paper by Horowitz et al. (2014).

PMID- 25579066
TI  - Mesencephalic origin of the rostral Substantia nigra pars reticulata.
AB  - In embryonic development, the neurons that will constitute a heterogeneous
      nucleus may have distinct origins. The different components of these populations
      reach their final location by radial and tangential migrations. The Substantia
      nigra pars reticulata (SNR) presents a high level of neuronal heterogeneity. It
      is composed by GABAergic neurons located in the mes-diencephalic basal plate.
      These inhibitory neurons usually display tangential migrations and it has been
      already described that the caudal SNR is colonized tangentially from rhombomere
      1. Our aim is to unveil the origin of the rostral SNR. We have localized a Nkx6.2
      positive ventricular domain located in the alar midbrain. Nkx6.2 derivatives'
      fate map analysis showed mainly a rostral colonization of this GABAergic neuronal
      population. We confirmed the mesencephalic origin by the expression of Six3. Both
      transcription factors are sequentially expressed along the differentiation of
      these neurons. We demonstrated the origin of the rostral SNR; our data allowed us
      to postulate that this nucleus is composed by two neuronal populations
      distributed in opposite gradients with different origins, one from rhombomere 1,
      caudal to rostral, and the other from the midbrain, rostral to caudal. We can
      conclude that the SNR has multiple origins and follows complex mechanisms of
      specification and migration. Our results support vital information for the study
      of genetic modifications in these extremely complex processes that result in
      devastating behavioral alterations and predisposition to psychiatric diseases.
      Understanding the development, molecular identity and functional characteristics
      of these diverse neuronal populations might lead to better diagnosis and
      treatment of several forms of neurological and psychiatric disease. 

PMID- 25579068
TI  - Comments on Bang et al.: the impact of recombinant parathyroid hormone on
      malignancies and mortality: 7 years of experience based on nationwide Danish
      registers.

PMID- 25579069
TI  - Treatment of Chlamydial infections: 2014 update.
AB  - INTRODUCTION: Chlamydiae are obligate intracellular bacterial pathogens whose
      entry into mucosal epithelial cells is required for intracellular survival and
      subsequent growth. The life cycle of Chlamydia spp. and the ability to cause
      persistent, often subclinical infection, has major ramifications for diagnosis
      and treatment of Chlamydia trachomatis and C. pneumoniae infections in humans.
      AREAS COVERED: This paper reviews the current literature on the antimicrobial
      susceptibilities and treatment of genital infections due to C. trachomatis and
      respiratory infections due to C. pneumoniae published since 2011. EXPERT OPINION:
      Chlamydiae are susceptible to antibiotics that interfere with DNA and protein
      synthesis, including tetracyclines, macrolides and quinolones, which are the
      compounds that have been most extensively studied and used for treatment of human
      infection. Since our original review was published in 2011, there have been some
      major advances in diagnostic tests for C. trachomatis and the introduction of the
      first FDA-approved test for the detection of C. pneumoniae in respiratory
      samples. However, the options for treating chlamydial infections have largely
      remained the same. There are a small number of new drugs currently in preclinical
      development and early clinical trials that may have a role in the treatment of
      chlamydial infections.

PMID- 25579067
TI  - Validation of 5 stage-of-change measures for parental support of healthy eating
      and activity.
AB  - OBJECTIVE: To assess the validity of 5 parental stage-of-change (SOC) measures:
      (1) providing 5 servings/d of fruits and vegetables (FV), (2) limiting television
      (TV) to 2 h/d, (3) helping children achieve 1 h/d physical activity (PA), (4)
      limiting sugary drinks (SD) to 1 serving/wk, and (5) limiting fruit juice (FJ) to
      4-6 oz/d. DESIGN: Cross-sectional instrument development study. Construct
      validity was evaluated by examining whether parental self-efficacy, parental
      readiness ladder (ladder), and child's behavioral levels (eg, FV consumption)
      exhibited a theoretically consistent pattern across the SOC.
      SETTING/PARTICIPANTS: Convenience sample (n = 283) of parents of children aged 4
      10 years. MEASURES: Survey assessed SOC, ladder, and child's behavioral level
      score for each topic (FV, TV, PA, SD, and FJ), and parental self-efficacy for
      measure except TV. ANALYSIS: Analysis of variance with Tukey-Kramer post hoc
      tests examined whether variables differed by SOC. RESULTS: Percentages of parents
      in the pre-action SOC were 34% (PA), 39% (FV), 42% (SD), 45% (TV), and 63% (FJ).
      Parental self-efficacy, ladder, and child's behavioral level differed
      significantly by SOC for each topic area (P < .001). Maintenance SOC was
      significantly higher than pre-action SOC. CONCLUSIONS AND IMPLICATIONS: Measured
      variables exhibited a theoretically consistent pattern across SOC, suggesting
      construct validity and potential usefulness for obesity prevention efforts.

PMID- 25579070
TI  - Clinical pharmacology of antifungal agents to overcome drug resistance in
      pediatric patients.
AB  - INTRODUCTION: Antifungal resistance is an emerging problem that increases
      morbidity and mortality in immunosuppressed pediatric patients, who suffer from
      invasive fungal diseases. Optimal pharmacological management is critical for the
      successful treatment of invasive fungal infections by resistant strains. AREAS
      COVERED: This paper reviews the mechanisms of resistance of different classes of
      antifungal agents and the current understanding of pediatric antifungal
      pharmacology for overcoming antifungal resistance in children based on laboratory
      and clinical studies in the English literature. The therapeutic choices against
      fungal pathogens with intrinsic or acquired resistance are further reviewed.
      EXPERT OPINION: There is a paucity of data in the pediatric population regarding
      the epidemiology of the resistant organisms to different antifungal agents. It is
      also unknown if there are more prevalent molecular mechanisms that promote
      antifungal resistance. Selection and dosages of the most effective antifungal
      agent for overcoming the antifungal resistance is crucial. However, there are
      limited studies guiding the optimal dosage and duration of treatment for
      management of emergent antifungal resistance. Further studies are warranted to
      elucidate the optimal pharmacology of the current antifungal agents against
      resistant organisms and to advance the development of new antifungal agents.

PMID- 25579072
TI  - [Importance of oxygen extraction tension in the management of cerebral hypoxia
      through brain tissue oxygen tension monitoring].

PMID- 25579073
TI  - The role of body size and physical activity on the risk of breast cancer in BRCA
      mutation carriers.
AB  - Women who inherit a BRCA mutation face a high lifetime risk of developing breast
      cancer. Given the high penetrance of these mutations, prevention is of extreme
      importance. Here, we review the literature regarding the role of body size and of
      physical activity in the context of BRCA-associated breast cancer. There is some
      evidence to support a protective role of a healthy body size and of regular
      physical activity among mutation carriers, particularly during adolescence or
      early adulthood. Factors which increase the physiologic expression of the normal
      copy of the BRCA1 or BRCA2 gene and thereby normalize protein levels, contribute
      to stem cell homeostasis, and/or affect hormone levels, might mitigate the
      effects of an inherited BRCA mutation. Preliminary evidence from one in vivo
      study and from one epidemiologic report suggests that an increase in BRCA1 mRNA
      expression occurs with increasing levels of physical activity. The prospect of
      changing lifestyle for the purpose of preventing breast cancer in high-risk
      women, complemented by mechanistic evidence, warrants evaluation in large-scale
      prospective studies. 

PMID- 25579082
TI  - The ups and downs of life: population expansion and bottlenecks of helminth
      parasites through their complex life cycle.
AB  - The fundamental assumption underpinning the evolution of numerous adaptations
      shown by parasites with complex life cycles is that huge losses are incurred by
      infective stages during certain transmission steps. However, the magnitude of
      transmission losses or changes in the standing crop of parasites passing from
      upstream (source) to downstream (target) hosts have never been quantified in
      nature. Here, using data from 100 pairs of successive upstream-downstream life
      stages, from distinct populations representing 10 parasite species, we calculated
      the total density per m2 of successive life stages. We show that clonal
      amplification of trematodes in their first intermediate host leads to an average
      4-fold expansion of numbers of individuals at the next life stage, when
      differences in the longevity of successive life stages are taken into account. In
      contrast, trophic transmission to the definitive host results in almost no
      numerical change for trematodes, but possibly in large decreases for
      acanthocephalans and nematodes, though a correction for longevity was not
      possible for the latter groups. Also, we only found a positive association
      between upstream and downstream stage densities for transmission involving free
      swimming cercariae in trematodes, suggesting a simple output-recruitment process.
      For trophic transmission, there was no coupling between downstream and upstream
      parasite densities. These first quantitative estimates of ontogenetic rises and
      falls in numbers under natural conditions provide new insights into the selective
      pressures acting on parasites with complex cycles. 

PMID- 25579081
TI  - "Not being able to talk was horrid": A descriptive, correlational study of
      communication during mechanical ventilation.
AB  - OBJECTIVES: The purpose of this study was to describe the patient experience of
      communication during mechanical ventilation. RESEARCH METHODOLOGY: This
      descriptive study is a secondary analysis of data collected to study the
      relationship between sedation and the MV patients' recall of the ICU. Interviews,
      conducted after extubation, included the Intensive Care Experience Questionnaire.
      Data were analysed with Spearman correlation coefficients (rs) and content
      analysis. SETTING: Participants were recruited from a medical-surgical intensive
      care unit in the Midwest United States. RESULTS: Participants (n = 31) with a
      mean age of 65 +/- 11.9 were on the ventilator a median of 5 days. Inability to
      communicate needs was associated with helplessness (rs = .43). While perceived
      lack of information received was associated with not feeling in control (rs = 41)
      and helplessness (rs = 41). Ineffective communication impacted negatively on
      satisfaction with care. Participants expressed frustration with failed
      communication and a lack of information received. They believed receipt of
      information helped them cope and desired a better system of communication during
      mechanical ventilation. CONCLUSION: Communication effectiveness impacts patients'
      sense of safety and well-being during mechanical ventilation. Greater emphasis
      needs to be placed on the development and integration of communication strategies
      into critical care nursing practice.

PMID- 25579083
TI  - Carotid stent extrusion following carotid blowout.
AB  - OBJECTIVE: We describe an unusual foreign body, a carotid stent extruded into the
      upper airway, and discuss the predisposing factors. METHODS: This is a single
      patient case report with review of the literature. RESULTS: Our patient is a 59
      year old female treated for T3N2aM0 (stage IVa) left tonsil squamous cell
      carcinoma who experienced a carotid blowout treated by carotid stent placement
      with subsequent carotid coiling and vessel takedown. Approximately ten months
      later, she coughed and expelled approximately 3cm of tubular stent-appearing
      material into her airway causing acute stridor and dysphagia. CT angiography
      (CTA) showed the distal and proximal stent in proper position without evidence of
      extravasation. The stent was extracted transorally showing the distal end of the
      carotid to be patent and covered by fibrin within its lumen. Review of the
      literature shows that such stent extrusions, although rare, do occur. CONCLUSION:
      Carotid stents are a valuable tool in cases of carotid blowout. However, long
      term data on patient prognosis is lacking. The foreign body response triggered by
      stent placement can cause dislodgement. The potential for stent extrusion is
      greatest in patients who have preexisting ulceration or who have undergone
      radiation, both common in head and neck cancer patients.

PMID- 25579084
TI  - Organization for rare diseases India (ORDI) - addressing the challenges and
      opportunities for the Indian rare diseases' community.
AB  - In order to address the unmet needs and create opportunities that benefit
      patients with rare disease in India, a group of volunteers created a not-for
      profit organization named Organization for Rare Diseases India (ORDI;
      www.ordindia.org). ORDI plans to represent the collective voice and advocate the
      needs of patients with rare diseases and other stakeholders in India. The ORDI
      team members come from diverse backgrounds such as genetics, molecular
      diagnostics, drug development, bioinformatics, communications, information
      technology, patient advocacy and public service. ORDI builds on the lessons
      learned from numerous similar organizations in the USA, European Union and
      disease-specific rare disease foundations in India. In this review, we provide a
      background on the landscape of rare diseases and the organizations that are
      active in this area globally and in India. We discuss the unique challenges in
      tackling rare diseases in India, and highlight the unmet needs of the key
      stakeholders of rare diseases. Finally, we define the vision, mission, goals and
      objectives of ORDI, identify the key developments in the health care context in
      India and welcome community feedback and comments on our approach.

PMID- 25579085
TI  - Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor
      genotyping and personalized medicine in a prospective trial across all tumor
      types.
AB  - Cell-free tumor DNA (ctDNA) has the potential to enable non-invasive diagnostic
      tests for personalized medicine in providing similar molecular information as
      that derived from invasive tumor biopsies. The histology-independent phase II
      SHIVA trial matches patients with targeted therapeutics based on previous
      screening of multiple somatic mutations using metastatic biopsies. To evaluate
      the utility of ctDNA in this trial, as an ancillary study we performed de novo
      detection of somatic mutations using plasma DNA compared to metastasis biopsies
      in 34 patients covering 18 different tumor types, scanning 46 genes and more than
      6800 COSMIC mutations with a multiplexed next-generation sequencing panel. In 27
      patients, 28 of 29 mutations identified in metastasis biopsies (97%) were
      detected in matched ctDNA. Among these 27 patients, one additional mutation was
      found in ctDNA only. In the seven other patients, mutation detection from
      metastasis biopsy failed due to inadequate biopsy material, but was successful in
      all plasma DNA samples providing three more potential actionable mutations. These
      results suggest that ctDNA analysis is a potential alternative and/or replacement
      to analyses using costly, harmful and lengthy tissue biopsies of metastasis,
      irrespective of cancer type and metastatic site, for multiplexed mutation
      detection in selecting personalized therapies based on the patient's tumor
      genetic content. 

PMID- 25579086
TI  - Molecular signatures of mRNAs and miRNAs as prognostic biomarkers in
      pancreatobiliary and intestinal types of periampullary adenocarcinomas.
AB  - Periampullary adenocarcinomas include four anatomical sites of origin (the
      pancreatic duct, bile duct, ampulla and duodenum) and most of them fall into two
      histological subgroups (pancreatobiliary and intestinal). Determining the exact
      origin of the tumor is sometimes difficult, due to overlapping histopathological
      characteristics. The prognosis depends on the histological subtype, as well as on
      the anatomical site of origin, the former being the more important. The molecular
      basis for these differences in prognosis is poorly understood. Whole-genome
      analyses were used to investigate the association between molecular tumor
      profiles, pathogenesis and prognosis. A total of 85 periampullary adenocarcinomas
      were characterized by mRNA and miRNA expressions profiling. Molecular profiles of
      the tumors from the different anatomical sites of origin as well as of the
      different histological subtypes were compared. Differentially expressed mRNAs and
      miRNAs between the two histopathological subtypes were linked to specific
      molecular pathways. Six miRNA families were downregulated and four were
      upregulated in the pancreatobiliary type as compared to the intestinal type (P <
      0.05). miRNAs and mRNAs associated with improved overall and recurrence free
      survival for the two histopathological subtypes were identified. For the
      pancreatobiliary type the genes ATM, PTEN, RB1 and the miRNAs miR-592 and miR
      497, and for the intestinal type the genes PDPK1, PIK3R2, G6PC and the miRNAs miR
      127-3p, miR-377* were linked to enriched pathways and identified as prognostic
      markers. The molecular signatures identified may in the future guide the
      clinicians in the therapeutic decision making to an individualized treatment, if
      confirmed in other larger datasets.

PMID- 25579087
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN): could
      retinoids play a causative role?
AB  - Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are overlapping
      manifestations on a spectrum of acute drug-induced conditions associated with
      severe blistering, skin peeling, and multi-organ damage. TEN is an eruption
      resembling severe scalding, with >=30% skin detachment. SJS is a mild form of
      TEN, characterized histologically by epidermal keratinocyte apoptosis with dermo
      epidermal separation and extensive small blisters with <10% body surface skin
      detachment. The syndrome can be induced by numerous medications and typically
      occurs 1-4 weeks after the initiation of therapy. Granulysin is found in the
      lesions of patients with SJS/TEN and plays a significant pathogenic role in the
      condition, but the overall mechanisms linking medications, granulysin, and
      disease manifestations remain obscure. This paper reviews evidence suggesting
      that the different medications implicated in SJS/TEN have the common property of
      interacting and synergizing with endogenous retinoids (vitamin A and its
      congeners), in many instances causing the latter to accumulate in and damage the
      liver, the main storage organ for vitamin A. It is hypothesized that liver damage
      leads to the spillage of toxic retinoid compounds into the circulation, resulting
      in an endogenous form of hypervitaminosis A and cytotoxicity with widespread
      apoptosis, mediated by granulysin and recognized as SJS/TEN. Subject to testing,
      the model suggests that symptom worsening could be arrested at onset by lowering
      the concentration of circulating retinoids and/or granulysin via phlebotomy or
      plasmapheresis or by pharmacological measures to limit their expression.

PMID- 25579091
TI  - Evaluation of drug-drug interaction between the novel cPLA2 inhibitor AK106
      001616 and methotrexate in rheumatoid arthritis patients.
AB  - 1. Drug interaction potential between AK106-001616, a novel cytosolic
      phospholipase A2 inhibitor, and methotrexate (MTX) in rheumatoid arthritis
      patients was investigated. This trial is registered with ClinicalTrials.gov,
      number NCT00902369. 2. In the clinical study, the 90% confidence intervals (CIs)
      for the geometric mean ratio (GMR) of AUC0-t of MTX administered after AK106
      001616 200 mg compared to the MTX without AK106-001616 were within 80-125%.
      However, administration of AK106-001616 at doses of 400 and 600 mg exceeded the
      125% threshold. As small but statistically significant increases in AUC0-t were
      observed, we investigated the mechanism for this drug-drug interaction between
      MTX and AK106-001616. 3. In vitro, AK106-001616 inhibited OAT1 (IC50 = 18.4 MUM,
      Ki = 33.6 MUM) in a non-competitive manner and OAT3 (IC50 = 1.80 MUM, Ki = 1.49
      MUM) in a competitive manner. Both transporters are involved in MTX transport in
      renal proximal tubules. 4. AK106-001616 has a weak drug interaction with MTX. In
      vitro studies provide a mechanistic understanding of the in vivo inhibition of
      transporters by AK106-001616.

PMID- 25579090
TI  - [Nosocomial infection due to Trichosporon asahii in a critical burned patient].
AB  - BACKGROUND: Invasive fungal infection is an important cause of morbimortality in
      patients with severe burns. The advances in burn care therapy have considerably
      extended the survival of seriously burned patients, exposing them to infectious
      complications, notably fungal infections, with increased recognition of invasive
      infections caused by Candida species. However, some opportunistic fungi, like
      Trichosporon asahii, have emerged as important causes of nosocomial infection.
      CASE REPORT: A case of nosocomial infection due to T. asahii in a severely ill
      burned patient successfully treated with voriconazole is presented. The
      management of invasive fungal infections in burned patients, from diagnosis to
      selection of the therapeutic protocol, is often a challenge. Early diagnosis and
      treatment are associated with a better prognosis. In this case report, current
      treatment options are discussed, and a review of previously published cases is
      presented. CONCLUSIONS: Due to the difficulty in the diagnosis of invasive
      mycoses and their high associated mortality rates, it is advisable to keep a high
      degree of clinical suspicion of trichosporonosis in susceptible patients,
      including burned patients. The isolation of T. asahii in clinical specimens of
      this type of host must raise clinical alert, since it may precede an invasive
      infection.

PMID- 25579106
TI  - Thiazolidinedione compounds: a patent review (2010 - present).
AB  - INTRODUCTION: The prevalence of metabolic syndrome, obesity and insulin
      resistance has become an epidemic. Thiazolidinediones (TZDs) affect glucose and
      lipid metabolism in insulin-sensitive tissues, which in turn reduces the lipid
      content in the liver by modulating several mediators. TZD as a hypoglycemic agent
      decrease blood sugar levels. Researchers have also made an attempt to design
      novel compounds having core structure of TZD with other heterocycles to explore
      them for anticancer and antimalarial properties. The present review provides an
      extended study of chemistry and inhibitory activity of established drug
      candidates containing TZDs, viz. their patenting scenario. AREAS COVERED: In this
      review, authors have covered TZD-based antidiabetic, anticancer and antimalarial
      drugs. MEDLINE and PubMed searches, and freedom of information available through
      FDA, USPTO, EPO and other patent database were used for the preparation of
      review. EXPERT OPINION: Diabetes management is very important as the number of
      diabetic patients increased and therefore the present research article will be
      very much useful for the development of new molecules.

PMID- 25579107
TI  - Use of primary high-risk human papillomavirus testing for cervical cancer
      screening: interim clinical guidance.
AB  - In 2011, the American Cancer Society, the American Society for Colposcopy and
      Cervical Pathology, and the American Society for Clinical Pathology updated
      screening guidelines for the early detection of cervical cancer and its
      precursors. Recommended screening strategies were cytology and cotesting
      (cytology in combination with hrHPV testing). These guidelines also addressed the
      use of hrHPV testing alone as a primary screening approach, which was not
      recommended for use at that time. There is now a growing body of evidence for
      screening with primary hrHPV testing, including a prospective US-based
      registration study. Thirteen experts including representatives from the Society
      of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology,
      American College of Obstetricians and Gynecologists, American Cancer Society,
      American Society of Cytopathology, College of American Pathologists, and the
      American Society for Clinical Pathology, convened to provide interim guidance for
      primary hrHPV screening. This guidance panel was specifically triggered by an
      application to the FDA for a currently marketed HPV test to be labeled for the
      additional indication of primary cervical cancer screening. Guidance was based on
      literature review and review of data from the FDA registration study,
      supplemented by expert opinion. This document aims to provide information for
      healthcare providers who are interested in primary hrHPV testing and an overview
      of the potential advantages and disadvantages of this strategy for screening as
      well as to highlight areas in need of further investigation. 

PMID- 25579108
TI  - Primary cervical cancer screening with human papillomavirus: end of study results
      from the ATHENA study using HPV as the first-line screening test.
AB  - OBJECTIVES: ATHENA evaluated the cobas HPV Test as the primary screen for
      cervical cancer in women >=25years. This reports the 3-year end-of-study results
      comparing the performance of HPV primary screening to different screening and
      triage combinations. METHODS: 42,209 women >=25years were enrolled and had
      cytology and hrHPV testing. Women with abnormal cytology (>=atypical squamous
      cells of undetermined significance) and those HPV positive were referred to
      colposcopy. Women not reaching the study endpoint of CIN2+ entered the 3-year
      follow-up phase. RESULTS: 3-year CIR of CIN3+ in cytology-negative women was 0.8%
      (95% CI; 0.5-1.1%), 0.3% (95% CI 0.1-0.7%) in HPV-negative women, and 0.3% (95%
      CI; 0.1-0.6%) in cytology and HPV negative women. The sensitivity for CIN3+ of
      cytology was 47.8% (95% CI; 41.6-54.1%) compared to 61.7% (95% CI; 56.0-67.5%)
      for the hybrid strategy (cytology if 25-29years and cotesting with cytology and
      HPV if >=30years) and 76.1% (95% CI; 70.3-81.8%) for HPV primary. The specificity
      for CIN3+ was 97.1% (95% CI; 96.9-97.2%), 94.6% (95% CI; 94.4-94.8%), and 93.5%
      (95% CI; 93.3-93.8%) for cytology, hybrid strategy, and HPV primary,
      respectively. Although HPV primary detects significantly more cases of CIN3+ in
      women >=25years than either cytology or hybrid strategy, it requires
      significantly more colposcopies. However, the number of colposcopies required to
      detect a single CIN3+ is the same as for the hybrid strategy. CONCLUSIONS: HPV
      primary screening in women >=25years is as effective as a hybrid screening
      strategy that uses cytology if 25-29years and cotesting if >=30years. However,
      HPV primary screening requires less screening tests.

PMID- 25579112
TI  - Calibration of pre-equilibrium HF-LPME and its application to the rapid
      determination of free analytes in biological fluids.
AB  - This study establishes a novel calibration method for pre-equilibrium hollow
      fiber liquid-phase microextraction (PE-HF-LPME), where the time constant of the
      extraction of the analyte from sample matrix to the extraction phase (organic
      solvent) is obtained from a simple concentration curve. Comparing to the
      traditional kinetic calibration method, where the time constant was obtained from
      the extraction time profile, the new calibration approach shows improved accuracy
      and precision. More importantly, deuterated standards are not required in the new
      method, thus significantly improving its cost-effectiveness and extending its
      applicability to a wide range of analytes lack of deuterated analogs serving as
      internal standards. In addition, mass spectrometry is not necessary for the
      quantification of analytes with the new calibration method, which may further
      extend the applicability of PE-HF-LPME to some laboratories without mass
      spectrometers. This study has been substantiated with both theoretical and
      experimental evidences. Further, the feasibility of the method for real
      biological samples was demonstrated by measuring the free concentration of
      flunitrazepam in urine and plasma samples and its drug-protein binding ratio in
      plasma. The results showed that the method had a short analysis time and was
      easily implemented with high accuracy and good reproducibility. 

PMID- 25579113
TI  - Isolation of alpha-linolenic acid biohydrogenation products by combined silver
      ion solid phase extraction and semi-preparative high performance liquid
      chromatography.
AB  - Polyunsaturated fatty acids typically found in cattle feed include linoleic (LA)
      and alpha-linolenic acid (ALA). In the rumen, microbes metabolize these resulting
      in the formation of biohydrogenation products (BHP), which can be incorporated
      into meat and milk. Bioactivities of LA-BHP, including conjugated linoleic acid
      (cis (c) 9,trans (t) 11-18:2 and t10,c12-18:2) and trans fatty acid isomers (t9-,
      t10- and t11-18:1) have been investigated, but effects of several BHP unique to
      ALA have not been extensively studied, and most ALA-BHP are not commercially
      available. The objective of the present research was to develop methods to purify
      and collect ALA-BHP using silver ion (Ag(+)) chromatography in sufficient
      quantities to allow for convenient bioactivity testing in cell culture. Fatty
      acid methyl esters (FAME) were prepared from perirenal adipose tissue from a cow
      enriched with ALA-BHP by feeding flaxseed. These were applied to Ag(+)-solid
      phase extraction, and eluted with hexane with increasing quantities of acetone
      (1, 2, 10, 20%) or acetonitrile (2%) to pre-fractionate FAME based on degree of
      unsaturation and double bond configuration. Fractions were collected,
      concentrated and applied to semi-preparative Ag(+)-high performance liquid
      chromatography (HPLC) for the isolation and collection of purified isomers, which
      was accomplished using isocratic elutions with hexane containing differing
      amounts of acetonitrile (from 0.015 to 0.075%). Purified trans-18:1 isomers
      collected ranged in purity from 88 to 99%. Purity of the ALA-BHP dienes
      collected, including c9,t13-18:2, t11,c15-18:2 and t10,c15-18:2, exceeded 90%,
      while purification of other dienes may require the use of other complementary
      procedures (e.g. reverse phase HPLC). 

PMID- 25579114
TI  - Extraction optimization of Loratadine by supramolecular solvent-based
      microextraction and its determination using HPLC.
AB  - Optimization of supramolecular solvent-based microextraction (SSME) of Loratadine
      and its determination with high-performance liquid chromatography (HPLC) with
      ultra violet (UV) detection were investigated. A factorial design (FD) and a
      central composite face-centered (CCF) were applied to evaluate the SSME
      procedure. The effect of four parameters on extraction efficiency was
      investigated. The factors studied were decanoic acid amount, percentage of
      tetrahydrofuran (THF) (v/v), pH and extraction time. According to half factorial
      design results, the effective parameters were decanoic acid amount, THF
      percentage (v/v) and pH. Then, a CCF was applied to obtain optimal condition. The
      optimized conditions were obtained at 110mg of decanoic acid, 10% of THF and
      pH=3. The limits of detection were in the range of 0.3-0.4ng/ml. Linearity of the
      method was determined to be in the range of 1.0-400.0ng/ml for distilled water
      and 1.3-400.0ng/ml for plasma. The extraction recovery was >92%. RSD for intra
      and inter day (n=5) of extraction of Loratadine were 3.1% and 6.2%, respectively.
      The developed method was successfully applied for the determination of Loratadine
      in distilled water and plasma samples. 

PMID- 25579116
TI  - Carbetocin for the prevention of postpartum hemorrhage: a systematic review and
      meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To compare the efficacy and safety profile of carbetocin with other
      uterotonic agents in preventing postpartum hemorrhage. METHODS: PubMed, Web of
      Science, Scopus and EBSCOhost were searched for relevant randomized controlled
      trials published until September 2013. RESULTS: Carbetocin was associated with a
      significantly reduced need for additional uterotonic agents (RR = 0.68, 95% CI:
      0.55-0.84, I(2 )= 4%) compared with oxytocin in women following cesarean
      delivery. However, with respect to postpartum hemorrhage, severe postpartum
      hemorrhage, mean estimated blood loss and adverse effects, our analysis failed to
      detect a significant difference. Studies comparing carbetocin with syntometrine
      in women undergoing vaginal delivery demonstrated no statistical difference in
      terms of risk of postpartum hemorrhage, severe postpartum hemorrhage or the need
      for additional uterotonic agents, but the risk of adverse effect was
      significantly lower in the carbetocin group. CONCLUSIONS: Carbetocin has been
      associated with a similar low incidence of adverse effects to oxytocin and at
      least as effective as syntometrine and may become an alternative uterotonic agent
      for the prevention of postpartum hemorrhage. Further studies should be conducted
      to determine the safety and efficacy profile of carbetocin in women with cardiac
      disorders and to analyze the cost-effectiveness and minimum effective dose of
      carbetocin.

PMID- 25579117
TI  - Fetal cerebellar damage in fetuses with severe anemia undergoing intrauterine
      transfusions.
AB  - OBJECTIVE: To evaluate radiologic findings and outcomes of cerebellar injuries in
      fetuses with severe anemia due to RhD alloimmunization undergoing intrauterine
      transfusions. METHODS: Imaging of multiplanar neurosonography and magnetic
      resonance imaging (MRI) were reviewed. Pregnancy outcomes were recorded. RESULTS:
      Cerebellar injuries were identified after the first intravascular transfusion in
      four fetuses. Two of these cases were previously reported. The median hemoglobin
      concentration was 2.1 g/dL. Prenatal neurosonography identified an echogenic
      collection involving the cerebellum suggestive for hemorrhage in three cases. A
      progressive hypoplasia of a hemisphere was demonstrated at follow-up examination
      in one of these cases. Hypoplasia of a cerebellar hemisphere was seen in the
      fourth fetus. Ultrasound diagnosis was confirmed by prenatal MRI in two cases. In
      the third case, the postnatal MRI showed as additional finding vermian
      involvement. One pregnancy was terminated and autopsy confirmed the presence of
      infratentorial hemorrhage. The remaining infants were delivered alive. At time of
      writing, a truncal ataxia was diagnosed in the child with vermian hypoplasia,
      while the other children have met all age-appropriate milestones. CONCLUSIONS: A
      severe anemia seems to put the fetus at risk of cerebellar damage, despite
      successful intravascular transfusion.

PMID- 25579115
TI  - Reproductive Health Issues for Adults with a Common Genomic Disorder: 22q11.2
      Deletion Syndrome.
AB  - 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome
      in humans. Survival to reproductive age and beyond is now the norm. Several
      manifestations of this syndrome, such as congenital cardiac disease and
      neuropsychiatric disorders, may increase risk for adverse pregnancy outcomes in
      the general population. However, there are limited data on reproductive health in
      22q11.2DS. We performed a retrospective chart review for 158 adults with
      22q11.2DS (75 male, 83 female; mean age 34.3 years) and extracted key variables
      relevant to pregnancy and reproductive health. We present four illustrative cases
      as brief vignettes. There were 25 adults (21 > age 35 years; 21 female) with a
      history of one or more pregnancies. Outcomes for women with 22q11.2DS, compared
      with expectations for the general population, showed a significantly elevated
      prevalence of small for gestational age liveborn offspring (p < 0.001),
      associated mainly with infants with 22q11.2DS. Stillbirths also showed elevated
      prevalence (p < 0.05). Not all observed adverse events appeared to be
      attributable to transmission of the 22q11.2 deletion. Recurring issues relevant
      to reproductive health in 22q11.2DS included the potential impact of maternal
      morbidities, inadequate social support, unsafe sexual practices, and delayed
      diagnosis of 22q11.2DS and/or lack of genetic counseling. These preliminary
      results emphasize the importance of early diagnosis and long term follow-up that
      could help facilitate genetic counseling for men and women with 22q11.2DS. We
      propose initial recommendations for pre-conception management, educational
      strategies, prenatal planning, and preparation for possible high-risk pregnancy
      and/or delivery.

PMID- 25579118
TI  - The Molecular Basis for the Post-Translational Addition of Amino Acids by L/F
      Transferase in the N-end Rule Pathway.
AB  - The N-end rule pathway is a conserved targeted proteolytic process observed in in
      organisms ranging from eubacteria to mammals. The N-end rule relates the
      metabolic stability of a protein to its N-terminal amino acid residue. The
      identity of the N-terminal amino acid residue is a primary degradation signal,
      often referred to as an N-degron, which is recognized by the components of the N
      End rule when it is a destabilizing N-termini. N-degrons may be exposed by non
      processive proteolytic cleavage or by post-translational modifications. One
      modification is the post-translational addition of amino acids to the N-termini
      of proteins, a reaction catalyzed by aminoacyl-tRNA protein transferases. The
      aminoacyl-tRNA protein transferase in eubacteria like Escherichia coli is L/F
      transferase. Recent investigations have reported unexpected observations
      regarding the L/F transferase catalytic mechanism and its mechanisms of substrate
      recognition. Additionally, recent proteome-wide identification of putative in
      vivo substrates facilitates hypothesis into the yet elusive biological functions
      of the prokaryotic N-end rule pathway. Here we summarize the recent findings on
      the molecular mechanisms of catalysis and substrate recognition by the E. coli
      L/F transferase in the prokaryotic N-end rule pathway.

PMID- 25579119
TI  - The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance
      in ovarian cancer cells.
AB  - OBJECTIVE: Ovarian cancer is the deadliest gynaecological cancer. A major
      contributor to the poor survival rate is the development of chemoresistance to
      platinum-based therapies such as cisplatin and carboplatin. Here we aimed to test
      the role of miRNAs in the acquisition of drug resistance in ovarian cancer.
      METHODS: We used microarrays to measure miRNA levels in the ovarian cancer cell
      line A2780 and its cisplatin-resistant derivative CP70. The role of miRNAs and
      the mRNA targets were tested using transfected miRNA mimics and siRNAs,
      respectively. Potential in vivo significance was investigated by analysing RNA
      levels in cohorts of ovarian cancer patients. RESULTS: We identified several
      miRNAs that are increased in cisplatin-resistant cells. We show that most of
      these do not directly contribute to cisplatin resistance. Interestingly, miR-21
      3p, the passenger strand of the known oncomiR, directed increased resistance to
      cisplatin in a range of ovarian cell lines. This effect was specific to the star
      strand, as miR-21-5p had the opposite effect and actually increased sensitivity
      of A2780 cells to cisplatin. We identify NAV3 as a potential target of miR-21-3p
      and show that knockdown of NAV3 increases resistance. Exosomes released by CP70
      cells were also capable of increasing resistance in A2780 cells, although this
      was independent of miR-21-3p. Finally, we use publically available transcriptomic
      data to demonstrate that miR-21-3p is raised, while NAV3 is reduced, in ovarian
      tumours that are resistant to platinum treatment. CONCLUSION: Our data suggest
      that miR-21-3p can induce cisplatin resistance in ovarian tumours, potentially by
      targeting the NAV3 gene.

PMID- 25579120
TI  - Pressure control of magnetic clusters in strongly inhomogeneous ferromagnetic
      chalcopyrites.
AB  - Room-temperature ferromagnetism in Mn-doped chalcopyrites is a desire aspect when
      applying those materials to spin electronics. However, dominance of high Curie
      temperatures due to cluster formation or inhomogeneities limited their
      consideration. Here we report how an external perturbation such as applied
      hydrostatic pressure in CdGeP2:Mn induces a two serial magnetic transitions from
      ferromagnet to non-magnet state at room temperature. This effect is related to
      the unconventional properties of created MnP magnetic clusters within the host
      material. Such behavior is also discussed in connection with ab initio density
      functional calculations, where the structural properties of MnP indicate magnetic
      transitions as function of pressure as observed experimentally. Our results point
      out new ways to obtain controlled response of embedded magnetic clusters.

PMID- 25579121
TI  - The anaplastic lymphoma kinase testing conundrum.
AB  - Given the excellent results of the clinical trials with anaplastic lymphoma
      kinase (ALK) inhibitors, the importance of accurately identifying ALK-positive
      lung carcinoma patients has never been greater. It brings with it a pressing need
      for harmonized development of companion diagnostics, for economic, scientific and
      medical reasons. Therefore, it is crucial that ALK testing assays become more
      standardized both in performance (analytical phase) and interpretation (post
      analytical phase). We find that both methods currently recommended by College of
      American Pathologists/International Association for the Study of Lung
      Cancer/Association for Molecular Pathology guidelines (FISH and
      Immunohistochemistry) are reasonable approaches for primary routine ALK testing,
      if at least 50 tumor cells are scored and protocols are strictly followed.
      Moreover, due to the high demand to study multiple predictive biomarkers on
      different assay platforms, quick and reliable approaches to achieve this are
      essential to guide treatment decisions. 

PMID- 25579134
TI  - A relationship between structural and electronic order-disorder effects and
      optical properties in crystalline TiO2 nanomaterials.
AB  - The focus of this paper is on the analysis of the structural and electronic order
      disorder effects at long, medium and short ranges of titanium dioxide (TiO2)
      nanoparticles synthesized by the sol-gel process followed by the microwave
      assisted solvothermal (MAS) method at low temperatures and short reaction times.
      X-ray diffraction (XRD), Rietveld refinement, micro-Raman (MR) spectroscopy,
      transmission electron microscopy (TEM) and X-ray spectroscopy (EDX) were used to
      characterize the TiO2 nanoparticles. Optical properties were investigated by
      ultraviolet-visible (UV-vis) and photoluminescence (PL) measurements performed at
      room temperature. XRD and Rietveld refinement confirmed the presence of the
      anatase and brookite phases; nonetheless anatase is the major phase. The X-ray
      photoelectron spectroscopy (XPS) analysis revealed the presence of only Ti(4+)
      but the nonstoichiometry revealed that TiO2 NPs contain defects assigned to
      oxygen vacancies that lead to structural and electronic order-disorder effects
      observed by band gap narrowing and PL wide band emission. These intermediary
      energy levels (shallow and deep levels) created within the band gap act as
      acceptors/donors of electrons and recombination centers. The oxygen vacancies
      (VO(x), VO and VO) responsible by degree of structural order-disorder are related
      to distortions (tilts) on the [TiO6] octahedron and changes in the bond lengths
      and bond angles between oxygen and titanium atoms that gave rise to new species
      of cluster makers such as [TiO6]', [TiO5.VO(x)], [TiO5.VO] and [TiO5.VO]. This
      structural transformation is consistent with a redistribution of electron density
      from highly ordered [TiO6](x) clusters which form distorted [TiO6]' as well as
      complex [TiO5.VO(x)], [TiO5.VO] and [TiO5.VO] clusters assigned to oxygen
      vacancies which were understood as displacements in the oxygen atoms' position in
      the bond lengths (Ti-O). 

PMID- 25579136
TI  - Know the signs and symptoms of diabetes.

PMID- 25579137
TI  - Probiotics, prebiotics & synbiotics in small intestinal bacterial overgrowth:
      opening up a new therapeutic horizon!

PMID- 25579133
TI  - Activated STAT5 confers resistance to intestinal injury by increasing intestinal
      stem cell proliferation and regeneration.
AB  - Intestinal epithelial stem cells (IESCs) control the intestinal homeostatic
      response to inflammation and regeneration. The underlying mechanisms are unclear.
      Cytokine-STAT5 signaling regulates intestinal epithelial homeostasis and
      responses to injury. We link STAT5 signaling to IESC replenishment upon injury by
      depletion or activation of Stat5 transcription factor. We found that depletion of
      Stat5 led to deregulation of IESC marker expression and decreased LGR5(+) IESC
      proliferation. STAT5-deficient mice exhibited worse intestinal histology and
      impaired crypt regeneration after gamma-irradiation. We generated a transgenic
      mouse model with inducible expression of constitutively active Stat5. In contrast
      to Stat5 depletion, activation of STAT5 increased IESC proliferation, accelerated
      crypt regeneration, and conferred resistance to intestinal injury. Furthermore,
      ectopic activation of STAT5 in mouse or human stem cells promoted LGR5(+) IESC
      self-renewal. Accordingly, STAT5 promotes IESC proliferation and regeneration to
      mitigate intestinal inflammation. STAT5 is a functional therapeutic target to
      improve the IESC regenerative response to gut injury. 

PMID- 25579138
TI  - Role of matrix metalloproteinases in physiological processes & disease.

PMID- 25579140
TI  - Evaluating the efficacy of probiotic on treatment in patients with small
      intestinal bacterial overgrowth (SIBO)--a pilot study.
AB  - BACKGROUND & OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) leads to
      several gastrointestinal (GI) problems and complications leading to
      malabsorption. The effectiveness of probiotics in the treatment of SIBO syndrome
      has not been well studied. This pilot study was aimed to assess the efficacy of a
      probiotic consisting of lactobacilli in the treatment of SIBO. METHODS: In this
      study, 30 cases suffering from chronic abdominal pain or diarrhoea and with a
      positive hydrogen breath test were randomized in a double-blind manner into two
      groups: probiotic drug user and control group. After an initial 3-week aggressive
      therapy with broad-spectrum antibiotics, a 15-day maintenance antibiotic therapy
      with lactol was administered for the study group and the same regimen without
      lactol for the control group. After six months the HBT result and the GI symptoms
      were analyzed and compared between the two groups. RESULTS: The result of
      hydrogen breath test and the clinical symptoms in patients receiving the
      maintenance regimen with lactol probiotic showed a better response. The hydrogen
      breath test turned negative in 93.3 per cent of those receiving lactol compared
      to 66.7 per cent of the controls. In all the cases receiving lactol, the
      abdominal pain disappeared completely ( p =0.002). In addition, other GI problems
      including flatulence, belching and diarrhoea significantly improved in the study
      group ( p < 0.05). INTERPRETATION & CONCLUSIONS: Based on the preliminary data it
      seems that adding lactol probiotic to the maintenance therapy of small intestinal
      bacterial overgrowth patients on routine antibiotic therapy will be beneficial in
      preventing the complications of this syndrome.

PMID- 25579141
TI  - Association of matrix metalloproteinase-7 (-181A/G) promoter polymorphism in
      chronic pancreatitis.
AB  - BACKGROUND & OBJECTIVES: Chronic pancreatitis is progressive and irreversible
      destruction of the pancreas. Matrix metalloproteinase-7 (MMP-7) is a secreted
      matrilysin, which contributes to angiogenesis and breakdown of basement membranes
      of pancreatic tissues. The present study was aimed to investigate the association
      of MMP-7 -181A/G (rs11568818) gene promoter polymorphism in patients with chronic
      pancreatitis. METHODS: A total of 100 chronic pancreatitis patients and 150
      unrelated healthy individuals were included in this case control study. The
      genotyping of the MMP-7 gene (- 181 A/G) (rs11568818) was carried out based on
      PCR-RFLP. The serum levels of MMP-7 were determined by ELISA. Association between
      genotypes and chronic pancreatitis was examined by odds ratio (OR) with 95%
      confidence interval (CI). RESULTS: The frequencies of the genotypes in promoter
      of MMP-7 were AA 49 per cent, AG 25 per cent and GG 26 per cent in chronic
      pancreatitis patients and AA 53 per cent, AG 38 per cent and GG 9 per cent in
      control subjects. Frequency of MMP-7 -181GG genotype and - 181G allele was
      significantly associated with chronic pancreatitis compared to healthy subjects
      [OR = 1.58 (95% CI: 1.06 -2.36), p =0.019]. There was no significant difference
      in the serum MMP-7 levels in the patients compared to control subjects.
      INTERPRETATION & CONCLUSIONS: The present study revealed a significant
      association of MMP-7 -181A/G (rs11568818) GG genotype with chronic pancreatitis
      patients, indicating its possible association with the disease.

PMID- 25579139
TI  - Genetic & epigenetic approach to human obesity.
AB  - Obesity is an important clinical and public health challenge, epitomized by
      excess adipose tissue accumulation resulting from an imbalance in energy intake
      and energy expenditure. It is a forerunner for a variety of other diseases such
      as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke,
      hyperlipidaemia and can be fatal leading to premature death. Obesity is highly
      heritable and arises from the interplay of multiple genes and environmental
      factors. Recent advancements in Genome-wide association studies (GWAS) have shown
      important steps towards identifying genetic risks and identification of genetic
      markers for lifestyle diseases, especially for a metabolic disorder like obesity.
      According to the 12th Update of Human Obesity Gene Map there are 253 quantity
      trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies.
      Contribution of genetic propensity of individual ethnic and racial variations in
      obesity is an active area of research. Further, understanding its complexity as
      to how these variations could influence ones susceptibility to become or remain
      obese will lead us to a greater understanding of how obesity occurs and
      hopefully, how to prevent and treat this condition. In this review, various
      strategies adapted for such an analysis based on the recent advances in genome
      wide and functional variations in human obesity are discussed.

PMID- 25579142
TI  - Relationship between promoter methylation & tissue expression of MGMT gene in
      ovarian cancer.
AB  - BACKGROUND & OBJECTIVES: Epigenetic alterations, in addition to multiple gene
      abnormalities, are involved in the genesis and progression of human cancers.
      Aberrant methylation of CpG islands within promoter regions is associated with
      transcriptional inactivation of various tumour suppressor genes. O 6-methyguanine
      DNA methyltransferase (MGMT) is a DNA repair gene that removes mutagenic and
      cytotoxic adducts from the O 6 -position of guanine induced by alkylating agents.
      MGMT promoter hypermethylation and reduced expression has been found in some
      primary human carcinomas. We studied DNA methylation of CpG islands of the MGMT
      gene and its relation with MGMT protein expression in human epithelial ovarian
      carcinoma. METHODS: A total of 88 epithelial ovarian cancer (EOC) tissue samples,
      14 low malignant potential (LMP) tumours and 20 benign ovarian tissue samples
      were analysed for MGMT promoter methylation by nested methylation-specific
      polymerase chain reaction (MSP) after bisulphite modification of DNA. A subset of
      64 EOC samples, 10 LMP and benign tumours and five normal ovarian tissue samples
      were analysed for protein expression by immunohistochemistry. RESULTS: The
      methylation frequencies of the MGMT gene promoter were found to be 29.5, 28.6 and
      20 per cent for EOC samples, LMP tumours and benign cases, respectively. Positive
      protein expression was observed in 93.8 per cent of EOC and 100 per cent in LMP,
      benign tumours and normal ovarian tissue samples. Promoter hypermethylation with
      loss of protein expression was seen only in one case of EOC. INTERPRETATION &
      CONCLUSIONS: Our results suggest that MGMT promoter hypermethylation does not
      always reflect gene expression.

PMID- 25579143
TI  - Renal cell carcinoma in India demonstrates early age of onset & a late stage of
      presentation.
AB  - BACKGROUND & OBJECTIVES: Clinical spectrum of most of the diseases in developing
      countries is different from the west. Similarly whether renal cell carcinomas
      (RCC) in a developing country like India is seen in the same spectrum in relation
      to the age at presentation as in the west is not described in the literature.
      This study was carried out to investigate the spectrum of RCC in India with
      regards to age of onset, stage at presentation and survival. METHODS: Patients
      with renal tumour, treated between January 2000 to December 2012 in a tertiary
      care hospital in north India, were analyzed for age at presentation, clinical
      features and histopathological characteristics. Clinical diagnosis was made by
      contrast enhanced computerized tomography (CECT) scans and/or magnetic resonance
      imaging (MRI). Renal masses diagnosed as angiomyolipoma, infective masses and
      hydatid cysts were excluded from the analysis. Impact of various age groups on
      gender, tumour size, TNM stage, Fuhrman grade, histopathological subtypes, lymph
      node, inferior vena cava (IVC) involvement and survival was analyzed. Patients
      were grouped in five age groups i.e. <=39, 40-49, 50-59, 60-69 and more than 70
      yr of age. RESULTS: Of the total 617 patients with 617 renal tumours (2 patients
      had bilateral tumours but only the larger tumour was considered) clinically
      suspected as RCC, 586 had epithelial cell tumour and the remaining 31 had non
      epithelial cell tumour. The mean tumour size was 8.08+/-3.5 cm (median 7, range 1
      25 cm). Tumour of less than 4 cm size was present in only 10.4 per cent patients.
      The mean age at diagnosis was 55.15+/-13.34 (median 56, range 14-91 yr) years. A
      total of 30.03 per cent of renal tumours presented in patients younger than 50 yr
      of age. Though there was no difference in stage, Fuhrman's grade, IVC involvement
      and lymph nodal spread among various age groups, younger patients had higher
      proportion of non clear cell RCC and only 48.59 per cent of them presented with
      conventional RCC. Mean survival was lower in patients younger than 39 yr with HR
      of 1.7 (0.8-3.2). INTERPRETATION & CONCLUSION: Our results showed that renal cell
      carcinoma was more frequent in younger people in India. One third of the patients
      were less than 50 yr of age and only 10.4 per cent patients had tumour of less
      than 4 cm (T1a). Younger patients of <39 yr of age had relatively lower survival
      rates.

PMID- 25579144
TI  - Propofol or sevoflurane anaesthesia does not affect hepatic integrity as assessed
      by the M30 & M65 cell death markers & liver enzymes.
AB  - BACKGROUND & OBJECTIVES: General anaesthetics may induce apoptosis. The pro
      apoptotic/necrotic markers M30 (caspase-cleaved cytokeratin-18) and M65 (intact
      cytokeratin-18) have been used to identify early apoptosis in liver disease. The
      aim of this study was to detect the effect of propofol and sevoflurane
      anaesthesia on these markers and blood transaminase levels in female patients
      undergoing elective surgery. METHODS: Sixty-seven women undergoing mastectomy or
      thyroidectomy under general anaesthesia were randomly allocated to the propofol
      or sevoflurane groups. Venous blood samples for measuring the apoptotic and
      necrotic markers M30 and M65 as well as for measuring the alanine
      aminotransferase (ALT) and the aspartate aminotransferase (AST) liver enzymes
      were collected before induction of anaesthesia, immediately after completion of
      surgery, and 24 and 48 h postoperatively. RESULTS: The M30 values preoperatively
      and 0, 24 and 48 h postoperatively were 280+/-229, 300+/-244, 267+/-198 and 254+/
      189 U/l in the propofol group and 237+/-95, 242+/-109, 231+/-94 and 234+/-127 U/l
      in the sevoflurane group, respectively. The M30 values did not differ within or
      between the groups. The M65 levels at the same time intervals were 470+/-262,
      478+/-271, 456+/-339 and 485+/-273 in the propofol group and 427+/-226, 481+/
      227, 389+/-158 and 404+/-144 U/l in the sevoflurane group, respectively. No
      significant changes were found in the M65 either within or between the propofol
      and the sevoflurane groups. The ALT and AST levels did not change at these time
      intervals. INTERPRETATION & CONCLUSIONS: Under the present study design propofol
      or sevoflurane anaesthesia did not induce apoptosis or affected the liver
      function as assessed by the M30, M65 markers and liver enzymes in patients
      undergoing mastectomy or thyroidectomy under general anaesthesia.

PMID- 25579145
TI  - Internal consistency & validity of Indian disability evaluation and assessment
      scale (IDEAS) in patients with schizophrenia.
AB  - BACKGROUND & OBJECTIVES: The Indian Disability Evaluation and Assessment Scale
      (IDEAS) has been recommended for assessment and certification of disability by
      the Government of India (GOI). However, the psychometric properties of IDEAS as
      adopted by GOI remain understudied. Our aim, thus, was to study the internal
      consistency and validity of IDEAS in patients with schizophrenia. METHODS: A
      total of 103 consenting patients with residual schizophrenia were assessed for
      disability, quality of life (QOL) and psychopathology using the IDEAS, WHO QOL
      100 and Positive and Negative symptom scale (PANSS) respectively. Internal
      consistency was calculated using Cronbach's alpha. For construct validity,
      relations between IDEAS, and psychopathology and QOL were studied. RESULTS: The
      inter-item correlations for IDEAS were significant with a Cronbach's alpha of
      0.721. All item scores other than score on communication and understanding; total
      and global IDEAS scores correlated significantly with the positive, negative and
      general sub-scales, and total PANSS scores. Communication and understanding was
      significantly related to negative sub-scale score only. Total and global
      disability scores correlated negatively with all the domains of WHOQOL-100
      (rho<0.01). The individual IDEAS item scores correlated negatively with various
      WHOQOL-100 domains (rho0< 0.01). INTERPRETATION & CONCLUSIONS: This study
      findings showed that the GOI-modified IDEAS had good internal consistency and
      construct validity as tested in patients with residual schizophrenia. Similar
      studies need to be done with other groups of patients.

PMID- 25579146
TI  - Use of computerized tests to evaluate psychomotor performance in children with
      specific learning disabilities in comparison to normal children.
AB  - BACKGROUND & OBJECTIVES: Children with specific learning disabilities (SpLD) have
      an unexplained difficulty in acquiring basic academic skills resulting in a
      significant discrepancy between their academic potential and achievements. This
      study was undertaken to compare the performance on a battery of six psychomotor
      tests of children with SpLD and those without any learning disabilities
      (controls) using computerized tests. METHODS: In this study, 25 children with
      SpLD and 25 controls (matched for age, socio-economic status and medium of
      instruction) were given three training sessions over one week. Then children were
      asked to perform on the six computerized psychomotor tests. RESULTS were compared
      between the two groups. RESULTS: Children with SpLD fared significantly worse on
      finger tapping test, choice reaction test, digit picture substitution test and
      card sorting test compared to the controls ( p <0.05). INTERPRETATION &
      CONCLUSIONS: Children with SpLD have impairment of psychomotor skills like
      attention, sensory-motor coordination and executive functioning. Further research
      is needed to evaluate if the remedial education plan results in improvement in
      psychomotor performance of children with SpLD on these selected tests.

PMID- 25579147
TI  - Nucleic acid amplification tests (NAATs) for gonorrhoea diagnosis in women:
      experience of a tertiary care hospital in north India.
AB  - BACKGROUND & OBJECTIVES: Gonorrhoea is among the most frequent of the estimated
      bacterial sexually transmitted infections (STIs) and has significant health
      implications in women. The use of nucleic acid amplification tests (NAATs) has
      been shown to provide enhanced diagnosis of gonorrhoea in female patients.
      However, it is recommended that an on-going assessment of the test assays should
      be performed to check for any probable sequence variation occurring in the
      targeted region. In this study, an in-house PCR targeting opa-gene of Neisseria
      gonorrhoeae was used in conjunction with 16S ribosomal PCR to determine the
      presence of gonorrhoea in female patients attending the tertiary care hospitals.
      METHODS: Endocervical samples collected from 250 female patients with complaints
      of vaginal or cervical discharge or pain in lower abdomen were tested using opa
      and 16S ribosomal assay. The samples were also processed by conventional methods.
      RESULTS: Of the 250 female patients included in the study, only one was positive
      by conventional methods (microscopy and culture) whereas 17 patients were found
      to be positive based on PCR results. INTERPRETATION & CONCLUSIONS: The clinical
      sensitivity of conventional methods for the detection of N. gonorrhoeae in female
      patients was low. The gonococcal detection rates increased when molecular method
      was used giving 16 additional positives. Studies should be done to find out other
      gene targets that may be used in the screening assays to detect the presence of
      gonorrhoea.

PMID- 25579149
TI  - A three year retrospective study on the increasing trend in seroprevalence of
      dengue infection from southern Odisha, India.
AB  - BACKGROUND & OBJECTIVES: In Odisha, several cases of dengue virus infection were
      detected for the first time in 2010, the importance of dengue as a serious
      mosquito-borne viral infection was felt only in 2011 with the reporting of many
      more positive cases. This retrospective three year study was done to find out the
      seroprevalence of dengue Ig m0 antibody and to know the predominant serotype of
      dengue virus among the patients suspected to have dengue virus infection in a
      tertiary care hospital in southern Odisha, India. METHODS: Blood samples from
      clinically suspected dengue cases admitted in the Medicine and Paediatrics
      departments of a tertiary care hospital were collected. These were processed for
      detection of dengue specific IgM antibody, carried out by the ELISA method.
      Dengue IgM antibody positive serum samples were tested for serotypic
      identification. RESULTS: Of the 5102 samples tested, 1074 (21.05%) were positive
      for dengue IgM. Maximum numbers of cases were found in 2012. Majority (47.86%) of
      cases were detected in the month of September. The most common affected age group
      was 11 to 20 yr. DENV1 and DENV2 were the detected serotypes. INTERPRETATION &
      CONCLUSIONS: Rapid increase in the dengue cases in 2012 became a public health
      concern as majority of cases were affecting the young adolescents. Most of the
      cases were reported in post-monsoon period indicating a need for acceleration of
      vector control programmes prior to arrival of monsoon.

PMID- 25579148
TI  - Estimation of vectorial capacity of Anopheles minimus Theobald & An. fluviatilis
      James (Diptera: Culicidae) in a malaria endemic area of Odisha State, India.
AB  - BACKGROUND & OBJECTIVES: Anopheles minimus and An. fluviatilis were incriminated
      as the major malaria vectors in Keonjhar district of Odisha State recently. This
      study was carried out to elucidate the potential role of these two vector species
      in transmission of malaria during different seasons, and vectorial capacity of
      these species was also estimated. METHODS: Three hilly and forested villages of
      Keonjhar district were randomly selected. Vectorial capacity (C) was calculated
      using the Macdonald's formula as modified by Garret-Jones. The human landing
      density of the vector species was obtained from all night human landing
      collections (bait protected by bed-net). Man feeding habit was estimated by
      multiplying the human blood index with feeding frequency, which was obtained on
      daily basis from the duration of gonotrophic cycle. The probability of survival
      through the extrinsic incubation cycle was calculated from the probability of
      survival through one day and duration of sporogonic cycle. RESULTS: The estimated
      vectorial capacity of An. minimus varied between 0.014 and 1.09 for Plasmodium
      falciparum (Pf) and between 0.1 and 1.46 for P. vivax (Pv). The C of An. minimus
      for both Pf and Pv was higher during rainy season than the other two seasons. The
      estimated C of An. fluviatilis varied between 0.04 and 1.28 for Pf and between
      0.20 and 1.54 for Pv. INTERPRETATION & CONCLUSIONS: Based on the estimated values
      of vectorial capacity of the two vector species, the area could be stratified and
      such stratification would reflect the difference in the intensity of transmission
      between different strata and accordingly the appropriate control strategy could
      be adopted for each stratum.

PMID- 25579150
TI  - Time dependent enhanced resistance against antibiotics & metal salts by
      planktonic & biofilm form of Acinetobacter haemolyticus MMC 8 clinical isolate.
AB  - BACKGROUND & OBJECTIVES: Available literature shows paucity of reports describing
      antibiotic and metal resistance profile of biofilm forming clinical isolates of
      Acinetobacter haemolyticus. The present study was undertaken to evaluate the
      antibiotic and metal resistance profile of Indian clinical isolate of A.
      haemolyticus MMC 8 isolated from human pus sample in planktonic and biofilm form.
      METHODS: Antibiotic susceptibility and minimum inhibitory concentration were
      determined employing broth and agar dilution techniques. Biofilm formation was
      evaluated quantitatively by microtiter plate method and variation in complex
      architecture was determined by scanning electron microscopy. Minimum biofilm
      inhibiting concentration was checked by Calgary biofilm device. RESULTS:
      Planktonic A. haemolyticus MMC 8 was sensitive to 14 antibiotics, AgNO 3 and HgC1
      2 resistant to streptomycin and intermediately resistant to netilmycin and
      kanamycin. MMC 8 exhibited temporal variation in amount and structure of biofilm.
      There was 32-4000 and 4-256 fold increase in antibiotic and metal salt
      concentration, respectively to inhibit biofilm over a period of 72 h as against
      susceptible planktonic counterparts. Total viable count in the range of 10(5)
      10(6) cfu / ml was observed on plating minimum biofilm inhibiting concentration
      on Muller-Hinton Agar plate without antimicrobial agents. Biofilm forming cells
      were several folds more resistant to antibiotics and metal salts in comparison to
      planktonic cells. Presence of unaffected residual cell population indicated
      presence of persister cells. INTERPRETATION & CONCLUSIONS: The results indicate
      that biofilm formation causes enhanced resistance against antibiotics and metal
      salts in otherwise susceptible planktonic A. haemolyticus MMC 8.

PMID- 25579151
TI  - NDM-1 (New Delhi metallo beta lactamase-1) producing Gram-negative bacilli:
      emergence & clinical implications.
AB  - BACKGOUND & OBJECTIVES: Resistance to carbapenems in Gram-negative bacteria
      conferred by NDM-1 is a global health problem. We investigated the occurrence of
      NDM-1 in clinical isolates of Gram-negative bacilli in a tertiary care hospital
      in Kashmir valley, India. METHODS: Gram-negative bacilli from different clinical
      isolates were included in the study. Antimicrobial susceptibility was performed
      by Kirby Bauer disk diffusion method and interpreted using Clinical Laboratory
      Standards Institute (CLSI) guidelines. Isolates resistant to carbapenems were
      subjected to different phenotypic test such as modified Hodge test (MHT), boronic
      acid and oxacillin based MHT ( BA-MHT and OXA-MHT), combined disk test and
      minimum inhibitory concentration (MIC) with imipenem and imipenem -EDTA for
      determination of class B metallo enzymes. Presence of blaNDM-1 gene was
      established by PCR and confirmed by sequencing. RESULTS: Of the total 1625 Gram
      negative isolates received, 100 were resistant to imipenem. Of the 100 isolates,
      55 (55%) were positive by modified Hodge test indicating carbapenemase
      production. Of the 100 isolates tested by MHT, BA-MHT and OXA-MHT, 29 (29%)
      isolates belonged to Class A and 15 (15%) to Class B, while 56 (56%) isolates
      were negative. Of the 15 class B metallo beta lactamase producers, nine carried
      the bla(NDM-1) gene. NDM-1 was found among Escherichia coli (2 isolates),
      Klebsiella pneumoniae (2 isolates), Citrobacter freundii (3 isolates),
      Acinetobacter spp (1 isolate), and one isolate of Pseudomonas aeruginosa.
      Isolates were resistant to all antibiotic tested except polymyxin B and
      tigecycline. INTERPRETATION & CONCLUSIONS: Our study showed the presence of
      clinical isolates expressing NDM-1 in Srinagar, Jammu & Kashmir, India. These
      isolates harbour plasmid mediated multiple drug resistant determinants and can
      disseminate easily across several unrelated genera. To halt their spread, early
      identification of these isolates is mandatory.

PMID- 25579152
TI  - Comparison of pulsed-field gel electrophoresis & repetitive sequence-based PCR
      methods for molecular epidemiological studies of Escherichia coli clinical
      isolates.
AB  - BACKGROUND & OBJECTIVES: PFGE, rep-PCR, and MLST are widely used to identify
      related bacterial isolates and determine epidemiologic associations during
      outbreaks. This study was performed to compare the ability of repetitive sequence
      based PCR (rep-PCR) and pulsed-field gel electrophoresis (PFGE) to determine the
      genetic relationships among Escherichia coli isolates assigned to various
      sequence types (STs) by two multilocus sequence typing (MLST) schemes. METHODS: A
      total of 41 extended-spectrum beta-lactamase- (ESBL-) and/or AmpC beta-lactamase
      producing E. coli clinical isolates were included in this study. MLST experiments
      were performed following the Achtman's MLST scheme and the Whittam's MLST scheme,
      respectively. Rep-PCR experiments were performed using the DiversiLab system.
      PFGE experiments were also performed. RESULTS: A comparison of the two MLST
      methods demonstrated that these two schemes yielded compatible results. PFGE
      correctly segregated E. coli isolates belonging to different STs as different
      types, but did not group E. coli isolates belonging to the same ST in the same
      group. Rep-PCR accurately grouped E. coli isolates belonging to the same ST
      together, but this method demonstrated limited ability to discriminate between E.
      coli isolates belonging to different STs. INTERPRETATION & CONCLUSIONS: These
      results suggest that PFGE would be more effective when investigating outbreaks in
      a limited space, such as a specialty hospital or an intensive care unit, whereas
      rep-PCR should be used for nationwide or worldwide epidemiology studies.

PMID- 25579153
TI  - Serological diagnosis of scrub typhus in patients attending a government hospital
      at Vellore, Tamil Nadu.

PMID- 25579154
TI  - Detection of AmpC beta-lactamases production in Acinetobacter species by
      inhibitor (disk) based & modified three dimensional (enzyme extraction) methods.

PMID- 25579155
TI  - A study on surgical site infections after trauma surgeries in a tertiary care
      hospital in north India.

PMID- 25579156
TI  - Huge neurofibroma of the scalp.

PMID- 25579157
TI  - Intranasal ectopic tooth.

PMID- 25579158
TI  - Through the eyes of young sibling donors: the hematopoietic stem cell donation
      experience.
AB  - This qualitative study used a grounded theory approach to explore how pediatric
      sibling donors of a successful hematopoietic stem cell transplantation
      conceptualized their donation experiences. Saving my sister's (or brother's) life
      describes the central phenomenon identified by this purposive sample of 8 sibling
      donors. Five themes captured their memories: being the perfect match, stepping
      up, worrying about the outcome, the waiting process, and sharing a special bond.
      Further research surrounding changes in relational issues will provide insight
      into inter-sibling support and the developmental course of the sibling
      relationship into adulthood when intensified by a health crisis. 

PMID- 25579160
TI  - Mitral valve repair for congenital mitral valve disease: impact of the use of a
      biodegradable annuloplasty ring.
AB  - BACKGROUND: This study compares the midterm results of mitral valve repair using
      the biodegradable ring versus repair with non-ring annuloplasty techniques for
      congenital mitral valve disease in young children where it was not possible to
      use standard commercial rings. METHODS: Between February 2006 and November 2011,
      68 patients underwent mitral valve repair for congenital mitral valve disease.
      Thirty-nine (57%) patients underwent concomitant annuloplasty using the
      biodegradable ring (group A) and 29 (43%) patients using non-ring annuloplasty
      techniques (group B). The median age of repair was 2 years (range 1 month to 14
      years). RESULTS: There were no hospital deaths or major postoperative morbidity.
      At a median follow-up of 3.8 years (range, 2 months to 5.1 years), overall
      survival at 5 years was 97% +/- 3% for group A and 88% +/- 8% for group B (p =
      0.29). Freedom from valve failure was 90% +/- 7% in group A and 74% +/- 9% in
      group B (p = 0.026). The freedom from reoperation was 100% in group A and 84% +/-
      9% in group B (p = 0.04). The mean transmitral gradients were 4.3 +/- 1.8 mm Hg
      in group A and 4.2 +/-1.7 mm Hg in group B (p = 0.77). CONCLUSIONS: Mitral valve
      repair using the biodegradable ring for congenital mitral valve disease was
      superior compared with non-ring annuloplasty repair. Excellent survival benefit,
      freedom from reoperation, and valve failure without significant elevation of
      transmitral gradients, suggests its important role in young children with smaller
      annular sizes where standard commercial rings are not available or recommended.

PMID- 25579159
TI  - A systematic review on TST and IGRA tests used for diagnosis of LTBI in
      immigrants.
AB  - BACKGROUND: High immigration rates from tuberculosis (TB) endemic countries to
      low-incidence countries have caused new TB guidelines in these countries to
      reconsider latent TB infection (LTBI) screening in these immigrants. OBJECTIVES:
      We performed a systematic review with the primary outcome of evaluating the
      number of cases recommended LTBI treatment with the tuberculin skin test (TST) or
      interferon gamma release assay (IGRA). Secondary objectives were to examine
      prevalence of positive LTBI diagnostic tests stratified by age and incidence of
      TB in country of origin. METHODS: We performed a systematic search of seven
      electronic databases for studies assessing TST and/or IGRA performance in
      immigrant populations to low incidence countries. Demographics, LTBI diagnosis,
      longitudinal TB development, and test result data were the primary data extracted
      from the studies. Prevalence of positive test data was stratified by age and
      country of origin. Studies were evaluated using a modified SIGN checklist for
      diagnostic studies. Data was compared using Fisher's exact test or chi (2) test,
      where appropriate. RESULTS: Our literature search yielded 51 studies (n = 34 TST,
      n = 9 IGRA, n = 8 both). Recommendation of LTBI treatment was less common in
      those tested with an IGRA compared to TST (p < 0.0001), while long-term
      development of active TB appears higher in those with a positive IGRA. There was
      no difference in the sensitivity and specificity of the IGRA and TST for
      prevalent TB (p > 0.05). Prevalence of a positive test was significantly lower in
      those who were <18 years of age compared to those >=18 years of age (p < 0.0001)
      and those from low TB incidence countries compared to high incidence countries (p
      < 0.0001) for both TST and IGRA. When comparing the two tests within the 2
      subgroups: age and TB incidence in country of origin, the prevalence of positive
      results was significantly lower for the IGRA than the TST (p < 0.0001).
      LIMITATIONS: The number of available studies evaluating the IGRA and longitudinal
      active TB development in those tested limits this study. CONCLUSION: Prevalence
      of positive test results were significantly lower in immigrants who were tested
      with an IGRA, resulting in fewer immigrants being recommended for LTBI treatment
      compared to TST. Coupled with comparable performance for detecting prevalent TB
      cases, the IGRA appears to exhibit better specificity than the TST and may be
      preferred as the standard of care for detecting LTBI in immigrants moving to low
      TB incidence countries.

PMID- 25579162
TI  - Nicorandil-associated ulceration of the gastrointestinal tract: side effects
      requiring surgical intervention.

PMID- 25579161
TI  - General anesthesia combined with epidural anesthesia ameliorates the effect of
      fast-track surgery by mitigating immunosuppression and facilitating intestinal
      functional recovery in colon cancer patients.
AB  - PURPOSE: The purpose of this study is to investigate the influence of anesthetic
      methods on markers of anti-tumor immunity and intestinal functions in fast-track
      surgery in colon cancer (CC) patients during the perioperative period. PATIENTS
      AND METHODS: A total of 53 patients with American Society of Anesthesiologists
      (ASA) I-II status randomly received general anesthesia (G group, n = 27) or
      general anesthesia combined with epidural anesthesia (E group, n = 26) for
      surgical tumor resection. The recovery times of intestinal function were
      evaluated in both groups postoperatively. The frequencies of different subsets of
      CD4+ T cells and myeloid-derived suppressor cells and C-reactive protein (CRP)
      were measured by flow cytometry and enzyme-linked immunosorbent assay,
      respectively, before anesthesia (t0), 1 h after the beginning of surgery (t1), 1
      h after the end of surgery (t2), and on day 2 (t3) and day 5 (t4) post-surgery.
      RESULTS: There was no significant difference in demographic characteristics
      between the two groups, but the E group of patients received significantly lower
      amounts of morphine and sevoflurane. In comparison with those in the G group,
      significantly greater numbers of lymphocytes and elevated frequencies of Th1
      cells were detected at t3 and t4 post-surgery in the E group (p < 0.01).
      Significantly lower percentages of Th2 cells and regulatory T cells were detected
      in the E group at t2-4 post-surgery. Whereas the levels of plasma CRP increased
      post-surgery in both groups, the levels of CRP were significantly lower in the E
      group than those in the G group at t3-4 post-surgery (p < 0.05). The times to the
      first flatus and to tolerate a full diet were significantly shorter in the E
      group than those in the G group (p < 0.01). CONCLUSION: General anesthesia
      combined with epidural anesthesia plays an important role in fast-track surgery,
      mitigating the surgical stress-related impairment of anti-tumor immune responses
      and hastening the recovery of intestinal function. This combination might also
      help to improve long-term outcomes for CC patients.

PMID- 25579165
TI  - Molecular response to imatinib in chronic myeloid leukaemia with a variant e13a3
      BCR-ABL1 fusion.
AB  - The majority of chronic myeloid leukaemia (CML) patients express either e13a2 or
      e14a2 BCR-ABL1 transcripts. Variant fusion genes can arise, usually due to
      alternative splicing of either BCR or ABL1 exons, with molecular monitoring by
      quantitative PCR (qPCR) in response to tyrosine kinase inhibitor therapy rarely
      reported in such cases. A case of CML is described in which an e13a3 BCR-ABL1
      fusion was characterised. A qPCR methodology was developed and applied
      prospectively to demonstrate a favourable molecular response to imatinib
      treatment. This case serves to highlight the requirement for molecular monitoring
      of those CML patients harbouring the e13a3 and other variant BCR-ABL1
      transcripts. 

PMID- 25579166
TI  - Peroxiredoxin 1 promotes tumorigenesis through regulating the activity of
      mTOR/p70S6K pathway in esophageal squamous cell carcinoma.
AB  - The biological function of Peroxiredoxin 1 (Prdx1) in cancer is still ambiguous,
      and its mechanism has not been elucidated so far. Previous studies have shown
      that Prdx1 functions as tumor suppressor in several types of cancers, but other
      studies have indicated that it is overexpressed in some types of human cancers,
      and inhibition of Prdx1 by shRNA contributes to radiosensitivity and
      chemosensitivity. In this study, a suppression subtractive hybridization cDNA
      library between esophageal squamous cell carcinoma (ESCC) cell line EC9706 and
      noncancerous esophageal epithelial cell line Het-1A was constructed, and 11
      tumorigenesis-associated genes including Prdx1 were isolated. In addition, we
      further confirmed that Prdx1 was overexpressed in ESCC cells at the level of
      protein compared with Het-1A (P < 0.05). Inhibition of Prdx1 by shRNA lentivirus
      decreased cell proliferation and invasion, and induced cell apoptosis, but did
      not affect cell cycle distribution of EC9706 cells (P > 0.05). Importantly, the
      total proteins of mTOR and p70S6K, as well as the activity of mTOR/p70S6K
      signaling pathway, were decreased in Prdx1-depletion EC9706 cells. Furthermore,
      the activity of mTOR/p70S6K signaling pathway was increased in Prdx1
      overexpressing Het-1A cells. These findings mentioned above demonstrate that
      Prdx1 may be involved in tumorigenesis through regulation of mTOR/p70S6K pathway
      in ESCC. 

PMID- 25579167
TI  - Peperotetraphin inhibits the proliferation of human prostate cancer cells via
      induction of cell cycle arrest and apoptosis.
AB  - Peperotetraphin (methyl rel-(1R,2S,3S)-2,3-bis(7-methoxy-1,3-benzodioxol-5-yl)
      cyclobutanecarboxylate) was a novel cyclobutane-type norlignan, which was
      isolated from the whole plant of Peperomia tetraphylla. In this study, we
      explored its anti-tumor effect and the molecular mechanism in human prostate
      cancer PC-3 cell lines. Firstly, cell viability was evaluated by Cell Counting
      Kit (CCK-8) assay. The PC-3 cells were treated with increasing concentrations of
      peperotetraphin for 24, 48 and 72 h, respectively. The results showed that
      peperotetraphin inhibited the growth of PC-3 cell in a dose- and time-dependent
      manner. Next, the cell cycle distributions were analyzed by flow cytometric
      analysis (FCM), and the data suggested that peperotetraphin could significantly
      induce cell cycle arrested at the G1-S phase transition. Then, the cell apoptosis
      was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL) and annexin V-FITC/PI dual staining analysis, the data confirmed
      apoptosis-inducing activity of peperotetraphin and the apoptosis rates increased
      from 3.9 to 32.3 % when treated with increasing concentrations of peperotetraphin
      from 0 to 50 uM. The expression levels of apoptosis-regulating protein caspase-3,
      Bax and Bcl-2 were also analyzed by Western blot analysis. The results showed
      that the expression levels of Bax and the activity of caspase-3 were upregulated,
      whereas the expression levels of Bcl-2 were downregulated compared with those of
      the control. These findings demonstrated that peperotetraphin exhibited effective
      cell growth inhibition by inducing cancer to undergo G1 phase arrest and
      apoptosis. The results suggested that peperotetraphin might have potential as
      chemoprevention or anti-tumor agent to prostatic cancer. 

PMID- 25579168
TI  - Sorafenib reverses resistance of gastric cancer to treatment by cisplatin through
      down-regulating MDR1 expression.
AB  - Cisplatin (DDP) has been successfully used in the treatment of gastric cancer;
      however, resistance of gastric tumors to cisplatin has also resulted in frequent
      treatment failure. To investigate the effect of sorafenib in reversing the
      resistance of human gastric cancer cell line SGC7901/DDP to treatment by
      cisplatin, and to examine possible underlying mechanisms. A SGC7901/DDP cell line
      was treated with different concentrations of sorafenib, with and without
      cisplatin. The reversing ability of sorafenib on cisplatin treatment was examined
      using MTT, FACS, and xenograft models. Western blotting and immunofluorescence
      were used to determine expressions of MDR1, p-Akt, and p-ERK. Sorafenib inhibited
      proliferation of human gastric cancer cell line SGC7901/DDP, both when used alone
      and in combination with cisplatin. Expression levels of MDR1, p-Akt, and p-ERK
      were significantly decreased after sorafenib treatment. Sorafenib may reverse
      resistance of human gastric cancer cell line SGC7901/DDP to cisplatin through
      down-regulating MDR1 expression. 

PMID- 25579169
TI  - Treatment on advanced NSCLC: platinum-based chemotherapy plus erlotinib or
      platinum-based chemotherapy alone? A systematic review and meta-analysis of
      randomised controlled trials.
AB  - We performed a systematic review and meta-analysis to assess the potential of
      erlotinib plus platinum-based chemotherapy relative to platinum-based
      chemotherapy alone for advanced non-small-cell lung cancer (NSCLC). Search of
      PubMed, EMBASE, Web of Science, CBM, CNKI, China Wan Fang databases and the
      Cochrane library was performed for studies regarding erlotinib plus platinum
      based chemotherapy for advanced NSCLC published between 1 January 2000 and 28
      August 2014. We identified eight eligible studies including 3,363 patients with
      advanced NSCLC. For PFS measure, an HR of 0.73 (0.58-0.93) with statistical
      significance was estimated when erlotinib plus platinum-based chemotherapy
      compared with platinum-based chemotherapy alone; objective response rate of 32.86
      versus 24.85 % was obtained for both groups, respectively. HR of 0.93 (0.86-1.00)
      with P of 0.170 was calculated for OS. We concluded that the erlotinib plus
      chemotherapy for advanced NSCLC could increase PFS and objective response rate,
      but not benefit OS. 

PMID- 25579170
TI  - Value of bimodal (18)F-choline-PET/MRI and trimodal (18)F-choline-PET/MRI/TRUS
      for the assessment of prostate cancer recurrence after radiation therapy and
      radical prostatectomy.
AB  - Between 27% and 53% of all patients who undergo radical prostatectomy (RP) or
      radiation therapy (RT) as the first-line treatment of prostate cancer (PCa)
      develop a biochemical recurrence. Imaging plays a pivotal role in restaging by
      helping to distinguish between local relapse and metastatic disease (i.e., lymph
      node and skeletal metastases). At present, the most promising tools for assessing
      PCa patients with biochemical recurrence are multiparametric magnetic resonance
      imaging (mpMRI) and positron emission tomography (PET)/computed tomography (CT)
      with radio-labeled choline derivatives. The main advantage of mpMRI is its high
      diagnostic accuracy in detecting local recurrence, while choline-PET/CT is able
      to identify lymph-node metastases when they are not suspicious on morphological
      imaging. The most recent advances in the field of fusion imaging have shown that
      multimodal co-registration, synchronized navigation, and combined interpretation
      are more valuable than the individual; separate assessment offered by different
      diagnostic techniques. The objective of the present essay was to describe the
      value of bimodal choline-PET/mpMRI fusion imaging and trimodal choline
      PET/mpMRI/transrectal ultrasound (TRUS) in the assessment of PCa recurrence after
      RP and RT. Bimodal choline-PET/mpMRI fusion imaging allows morphological,
      functional, and metabolic information to be combined, thereby overcoming the
      limitations of each separate imaging modality. In addition, trimodal real-time
      choline-PET/mpMRI/TRUS fusion imaging may be useful for the planning and real
      time guidance of biopsy procedures in order to obtain histological confirmation
      of the local recurrence. 

PMID- 25579171
TI  - Hepatic lymphatics: anatomy and related diseases.
AB  - The liver normally produces a large amount of lymph. It is estimated that between
      25% and 50% of the lymph received by the thoracic duct comes from the liver. In
      normal conditions, hepatic lymphatics are not depicted on cross-sectional
      imaging. They are divided in lymphatics of deep system (lymphatics following the
      hepatic veins and the portal tract) and those of superficial system (convex
      surface and inferior surface). A variety of diseases may affect hepatic
      lymphatics and in general they manifest as lymphedema, lymphatic mass, or cystic
      lesions. Abnormal distended lymphatics are especially seen in periportal spaces
      as linear hypoattenuations on CT or strong linear hyperintensities on heavily T2
      weighted MR imaging. Lymphatic tumor spread as in lymphoma and lymphangitic
      carcinomatosis manifests as periportal masses and regional lymph node
      enlargement. Lymphatic disruption after trauma or surgery is depicted as
      perihepatic fluid collections of lymph (lymphocele). Lymphatic malformation such
      as lymphangioma is seen on imaging as cystic spaces of variable size. 

PMID- 25579173
TI  - Effect of shape on the self-assembly of faceted patchy nanoplates with irregular
      shape into tiling patterns.
AB  - Recent reports of the synthesis and assembly of faceted nanoplates with a wide
      range of shapes and composition motivates the possibility of a new class of two
      dimensional materials with specific patterns targeted for a host of exciting
      properties. Yet, studies of how nanoplate shape controls their assembly -
      knowledge necessary for their inverse design from target structures - has been
      performed for only a handful of systems. By constructing a general framework in
      which many known faceted nanoplates may be described in terms of four anisotropy
      dimensions, we discover design rules to guide future synthesis and assembly. We
      study via Monte Carlo simulations attractive polygons whose shape is altered
      systematically under the following four transformations: faceting, pinching,
      elongation and truncation. We report that (i) faceting leads to regular porous
      structures (ii) pinching stabilizes complex structures such as dodecagonal
      quasicrystals (iii) elongation leads to asymmetric phase behavior, where low and
      high aspect ratio nanoplates self-assemble completely different structures and
      (iv) low and high degrees of truncation transform a complex self-assembler into a
      disk-like assembler, providing design ideas that could lead to switchable
      structures. We provide important insight into how the shape and attractive
      interactions of a nanoplate can be exploited or designed to target specific
      classes of structures, including space-filling, porous, and complex tilings. 

PMID- 25579172
TI  - Intratumoral artery on contrast-enhanced computed tomography imaging:
      differentiating intrahepatic cholangiocarcinoma from poorly differentiated
      hepatocellular carcinoma.
AB  - AIM: Differentiating intrahepatic cholangiocarcinoma (ICC) from poorly
      differentiated hepatocellular carcinoma (p-HCC) is often difficult, but it is
      important for providing appropriate treatments. The purpose of this study was to
      examine the features differentiating ICC from p-HCC on contrast-enhanced dynamic
      computed tomography (CT). METHODS: This study examined 42 patients with
      pathologically confirmed ICC (n = 19) or p-HCC (n = 23) for which contrast
      enhanced dynamic CT data were available. CT images were analyzed for enhancement
      patterns during the arterial phase, washout pattern, delayed enhancement,
      satellite nodules, capsular retraction, lesion shape, and presence of an
      intratumoral hepatic artery, intratumoral hepatic vein, intratumoral portal vein,
      and bile duct dilation around the tumor, portal vein tumor thrombus, lobar
      atrophy, or lymphadenopathy. RESULTS: Univariate analysis revealed the presence
      of rim enhancement (p = 0.037), lobulated shape (p = 0.004), intratumoral artery
      (p < 0.001), and bile duct dilation (p = 0.006) as parameters significantly
      favoring ICC, while a washout pattern significantly favored p-HCC (p < 0.001).
      Multivariate analysis revealed intratumoral artery as a significant, independent
      variable predictive of ICC (p = 0.037), and 15 ICCs (78.9%) showed this feature.
      Washout pattern was a significant, independent variable favoring p-HCC (p =
      0.049), with 15 p-HCCs (65.2%) showing this feature. CONCLUSION: The presence of
      an intratumoral artery in the arterial phase on contrast-enhanced dynamic CT was
      a predictable finding for ICC, and the presence of a washout pattern was a
      predictable finding for p-HCC, differentiating between ICC and p-HCC.

PMID- 25579174
TI  - 5-Hydroxymethylcytosine: An epigenetic mark frequently deregulated in cancer.
AB  - The epigenetic mark 5-hydroxymethylcytosine (5hmC) has gained interest since
      2009, when it was discovered that Ten-Eleven-Translocation (TET) proteins
      catalyze the conversion of 5-methylcytosine (5mC) into 5hmC. This conversion
      appears to be an intermediate step in the active DNA demethylation pathway.
      Factors that regulate DNA hydroxymethylation are frequently affected in cancer,
      leading to deregulated 5hmC levels. In this review, we will discuss the
      regulation of DNA hydroxymethylation, defects in this pathway in cancer, and
      novel therapies that may correct deregulated (hydroxy)methylation of DNA.

PMID- 25579175
TI  - Characterization of phenolic constituents inhibiting the formation of sulfur
      containing volatiles produced during garlic processing.
AB  - Garlic (Allium sativum L.), which is a widely distributed plant, is globally used
      as both spice and food. This study identified five novel phenolic compounds,
      namely, 8-(3-methyl-(E)-1-butenyl)diosmetin, 8-(3-methyl-(E)-1-butenyl)chrysin, 6
      (3-methyl-(E)-1-butenyl)chrysin, and Alliumones A and B, along with nine known
      compounds 6-14 from the ethanol extract of garlic. The structures of these five
      novel phenolic compounds were established via extensive 1D- and 2D-nuclear
      magnetic resonance spectroscopy experiments. The effects of the phenolic
      compounds isolated from garlic on the enzymatical or nonenzymatical formation of
      sulfur-containing compounds produced during garlic processing were examined.
      Compound 12 significantly reduced the thermal decomposition of alliin, whereas
      compound 4 exhibited the highest percentage of alliinase inhibition activity
      (36.6%). 

PMID- 25579176
TI  - Resveratrol decreases oxidative burst capacity and alters stimulated leukocyte
      cytokine production in vitro.
AB  - INTRODUCTION: Resveratrol, a naturally-occurring phytophenol, has been shown to
      bolster immune surveillance and reverse immunosenescence in a dose dependent
      manner in rodents and humans. Although safety and pharmacokinetic studies have
      been completed in dogs, the immunomodulatory effects of resveratrol in dogs has
      not yet been investigated. The objective of this study was to determine the
      effect of resveratrol on canine innate immune system function in vitro. The
      hypothesis was that similar to other species, low concentrations of resveratrol
      would stimulate while high concentrations would depress innate immune system
      function. METHODS: Whole blood was collected from six healthy, adult, client
      owned dogs and was incubated with resveratrol at final concentrations of 6000 ng
      ml(-1), 3000 ng ml(-1), 1000 ng ml(-1), or control solution for 4h. Following
      incubation, phagocytosis and oxidative burst were evaluated using flow cytometry,
      and LPS-, lipoteichoic acid (LTA) - and peptidoglycan (PG)-stimulated leukocyte
      production of TNF, IL-6, and IL-10 were measured using a canine specific
      multiplex assay. RESULTS: Phagocytosis was not altered by resveratrol at any
      concentration compared to control. However, while the number of PMNs capable of
      performing oxidative burst did not change, the robustness of the reaction
      following stimulation with Escherichia coli and PMA was reduced in a dose
      dependent manner. In addition, LPS-, LTA-, PG, and PBS-stimulated TNF production
      was increased following incubation with all concentrations of resveratrol
      compared to control, and this effect was dose dependent. LTA-stimulated IL-6 was
      increased with resveratrol compared to control. Furthermore, LTA-stimulated IL-10
      was decreased with 6000 ng ml(-1) and 3000 ng ml(-1) concentrations of
      resveratrol and PG-stimulated IL-10 production was decreased with all
      concentrations of resveratrol compared to control. The LPS-, LTA-, and PG
      stimulated TNF:IL-10 ratio was increased with 6000 ng ml(-1) of resveratrol
      compared to control and lower resveratrol concentrations. CONCLUSION: While
      resveratrol was sparing to PMN phagocytosis, it reduced the robustness of PMN
      oxidative burst. Resveratrol also increased pro-inflammatory and decreased anti
      inflammatory leukocyte cytokine production capacity in vitro. These data suggest
      that resveratrol supplementation may depress oxidative burst reactions while
      promoting pro-inflammatory leukocyte cytokine production and decreasing anti
      inflammatory cytokine production. Based on these findings, further in vivo study
      regarding the effects of resveratrol on PMN oxidative burst capability and
      leukocyte cytokine production capacity are indicated prior to routine
      supplementation.

PMID- 25579177
TI  - NKD2, a negative regulator of Wnt signaling, suppresses tumor growth and
      metastasis in osteosarcoma.
AB  - Osteosarcoma (OS) is the most frequent pediatric malignant bone tumor that has a
      high propensity for metastases. Through osteoblast-specific alteration of p53
      status, we developed a genetically engineered mouse model of localized and
      metastatic OS to gain an understanding into the molecular pathogenesis of OS.
      Microarray analysis of both localized tumors and metastatic tumors identified the
      downregulation of the naked cuticle homolog 2 (NKD2) gene, a negative regulator
      of Wnt signaling. Overexpression of NKD2 in metastatic human and mouse OS cells
      significantly decreases cell proliferation, migration and invasion ability in
      vitro and drastically diminishes OS tumor growth and metastasis in vivo, whereas
      downregulation enhances migratory and invasive potential. Evaluation of NKD2
      overexpressing tumors revealed upregulation of tumor-suppressor genes and
      downregulation of molecules involved in blood vessel formation and cell
      migration. Furthermore, assessment of primary human OS revealed downregulation of
      NKD2 in metastatic and recurrent OS. Finally, we provide biological evidence that
      use of small-molecule inhibitors targeting the Wnt pathway can have therapeutic
      efficacy in decreasing metastatic properties in OS. Our studies provide
      compelling evidence that downregulation of NKD2 expression and alterations in
      associated regulated pathways have a significant role in driving OS tumor growth
      and metastasis. 

PMID- 25579179
TI  - Semiclassical TEM image formation in phase space.
AB  - Current developments in TEM such as high-resolution imaging at low acceleration
      voltages and large fields of view, the ever larger capabilities of hardware
      aberration correction and the systematic shaping of electron beams require
      accurate descriptions of TEM imaging in terms of wave optics. Since full quantum
      mechanic solutions have not yet been established for, e.g., the theory of
      aberrations, we are exploring semiclassical image formation in the TEM from the
      perspective of quantum mechanical phase space, here. Firstly, we use two well
      known semiclassical approximations, Miller's semiclassical algebra and the frozen
      Gaussian method, for describing the wave optical generalization of arbitrary
      geometric aberrations, including nonisoplanatic and slope aberrations. Secondly,
      we demonstrate that the Wigner function representation of phase space is well
      suited to also describe incoherent aberrations as well as the ramifications of
      partial coherence due to the emission process at the electron source. We identify
      a close relationship between classical phase space and Wigner function
      distortions due to aberrations as well as classical brightness and quantum
      mechanical purity. 

PMID- 25579178
TI  - A long non-coding RNA links calreticulin-mediated immunogenic cell removal to RB1
      transcription.
AB  - A subset of promoters bidirectionally expresses long non-coding RNAs (ncRNAs) of
      unknown function and protein-coding genes (PCGs) in parallel. Here, we define a
      set of 1107 highly conserved human bidirectional promoters that mediate the
      linked expression of long ncRNAs and PCGs. Depletion of the long ncRNA expressed
      from the RB1 promoter, ncRNA-RB1, reveals regulatory effects different from the
      RB1-controlled transcriptional program. ncRNA-RB1 positively regulates the
      expression of calreticulin (CALR) that in response to certain therapeutic
      interventions can translocate from the endoplasmic reticulum to the cell surface,
      hence activating anticancer immune responses. Knockdown of ncRNA-RB1 in tumor
      cells reduced expression of CALR, impaired the translocation of the protein to
      the cell surface upon treatment with anthracylines and consequently inhibited the
      cellular uptake by macrophages. In conclusion, co-transcription of ncRNA-RB1 and
      RB1 provides a positive link between the expression of the two tumor suppressors
      RB1 and the immune-relevant CALR protein. This regulatory interplay exemplifies
      disease-relevant co-regulation of two distinct gene products, in which loss of
      expression of one oncosuppressor protein entails the abolition of additional
      tumor-inhibitory mechanisms. 

PMID- 25579180
TI  - HPV DNA genotyping and methylation of gene p16 INK4A in cervical LSIL.
AB  - BACKGROUND: DNA methylation is the most important epigenetic change involved in
      the control of gene expression in human cells. Methylation of the p16(INK4a) gene
      occurs early in the development of cervical cancer. Low-grade squamous
      intraepithelial lesions (LSILs) are prevalent, and their behavior is variable.
      OBJECTIVE: To identify the HPV DNA type, detect the methylation status of the
      p16(INK4A) gene, and analyze their association with the cytological evolution of
      LSIL over a period of two years. METHODS: We conducted a cohort study with 40
      participants. Cervical scrapings were collected for cytological and molecular
      analysis. HPV DNA detection and typing were performed by means of polymerase
      chain reaction (PCR) and restriction fragment length polymorphism (RFLP).
      Methylation-specific PCR was performed to detect methylation. RESULTS: HPV DNA
      was detected in 87% of the cases, and type 16 was the most frequent type.
      Methylation was detected in 11% of the cases and did not exhibit a significant
      correlation with the HPV type. Unfavorable cytological evolution exhibited a
      significant association with the presence of methylation. CONCLUSION: HPV 16 was
      the most frequently detected type of HPV in LSIL. Methylation of the p16(INK4A)
      gene was infrequent and occurred independent of the presence of HPV DNA.
      Methylation of the p16(INK4a) gene exhibited a significant correlation with
      persistence/progression of LSIL.

PMID- 25579182
TI  - Edge-to-edge interaction between carbon nanotube-pyrene complexes and electrodes
      for biosensing and electrocatalytic applications.
AB  - We demonstrate here that the edge-to-edge interaction between carbon nanotubes
      (CNTs) and edge plane electrodes plays an important role in exposing a large
      proportion of the basal planes of the CNTs to allow enhanced pi-pi stacking of a
      pyrenyl compound and subsequent high density protein immobilization yielding
      large electrocatalytic currents. 

PMID- 25579181
TI  - TIMP-2 gene methylation in cervical precursor and invasive lesions.
AB  - OBJECTIVE: To analyze the presence of HPV-DNA and TIMP-2 gene methylation in
      cervical precursor and invasive lesions, as well as to study the associations
      among the latter, the presence of HPV-DNA, and the clinical evolution of such
      lesions. METHODS: Cross-sectional study that includes 49 biopsy or brush smear
      samples from women with a normal cervix, LSIL, HSIL, microinvasive carcinoma and
      invasive carcinoma. The presence of HPV-DNA and specific methylation was analyzed
      using PCR. Thirty-eight biopsy samples for HSIL, microinvasive carcinoma and
      frank invasive carcinoma as well as 11 brush smear samples for LSIL and normal
      cervices were analyzed. RESULTS: TIMP-2 gene methylation was detected in 86.8%
      (33/38) of the samples from the group with lesions and 50% (4/8) of the normal
      samples (p=0.03). HPV-DNA was detected in 81.6% (31/38) of the samples from the
      group with lesions and 25% (2/8) of the normal samples (p=0.003). HPV-DNA was
      more frequent in the methylated samples (50%), and the group with methylation had
      a higher risk of unfavorable evolution than the group without methylation;
      however, such observations were not statistically significant (p=0.19).
      CONCLUSION: TIMP-2 gene methylation and the presence of HPV-DNA were
      characteristic of the group with cervical lesions. Methylation was not associated
      with the presence of HPV-DNA or an unfavorable clinical evolution.

PMID- 25579191
TI  - Comparative NMR analysis of collagen triple helix organization from N- to C
      termini.
AB  - The collagen triple helix consists of three supercoiled solvent-exposed
      polypeptide chains, and by dry weight it is the most abundant fold in mammalian
      tissues. Many factors affecting the structure and stability of collagen have been
      determined through the use of short synthetically prepared peptides, generally
      called collagen-mimetic peptides (CMPs). NMR (nuclear magnetic resonance
      spectroscopy) investigations into the molecular structure of CMPs have suffered
      from large amounts of signal overlap and degeneracy because of collagen's
      repetitive primary sequence, the close and symmetric packing of the three chains
      and the identical peptide sequences found in homotrimers. In this paper a peptide
      library is prepared in which a single isotopic (15)N-Gly label is moved
      sequentially along the peptide backbone. Our approach allows for a more explicit
      examination of local topology than available in past reports. This reveals larger
      regions of disorder at the C-terminus than previously detected by
      crystallographic or NMR studies, and here C-terminal fraying is seen to extend
      for six amino acids in a (POG)10 sequence. Furthermore, small sequence changes at
      the N-terminus greatly influence the degree of this localized disorder and may be
      useful in the future design of CMPs to maximize collagen's interstrand hydrogen
      bonding pattern. Our approach and data serves as a reference for future CMP
      characterizations to determine the quality and extent of folding. 

PMID- 25579193
TI  - Going beyond E. coli: autotransporter based surface display on alternative host
      organisms.
AB  - Autotransporters represent one of the most popular anchoring motifs used to
      display peptides, proteins or enzymes on the cell surface of a Gram-negative
      bacterium. Applications range from vaccine delivery to library screenings to
      biocatalysis and bioremediation. Although the underlying secretion mechanism is
      supposed to be available in most, if not all, Gram-negative bacteria,
      autotransporters have to date almost exclusively been used for surface display on
      Escherichia coli. However, for their utilisation beyond a laboratory scale, in
      particular for biocatalysis, host bacteria with specific features and industrial
      applicability are required. A few groups have addressed this issue and
      demonstrated that bacteria other than E. coli can also be used for
      autotransporter based surface display. We summarise these studies and discuss
      opportunities and challenges that arise from surface display of recombinant
      proteins using the autotransporter pathway in alternative hosts. 

PMID- 25579194
TI  - Advances in protease engineering for laundry detergents.
AB  - Proteases are essential ingredients in modern laundry detergents. Over the past
      30 years, subtilisin proteases employed in the laundry detergent industry have
      been engineered by directed evolution and rational design to tailor their
      properties towards industrial demands. This comprehensive review discusses recent
      success stories in subtilisin protease engineering. Advances in protease
      engineering for laundry detergents comprise simultaneous improvement of thermal
      resistance and activity at low temperatures, a rational strategy to modulate pH
      profiles, and a general hypothesis for how to increase promiscuous activity
      towards the production of peroxycarboxylic acids as mild bleaching agents. The
      three protease engineering campaigns presented provide in-depth analysis of
      protease properties and have identified principles that can be applied to improve
      or generate enzyme variants for industrial applications beyond laundry
      detergents. 

PMID- 25579195
TI  - Development, reliability and validity of Traditional Chinese Medicine Health Self
      Evaluation Scale (TCM-50).
AB  - OBJECTIVE: To develop a health-evaluating scale from a Chinese medicine (CM)
      perspective and reflecting CM conception of health. METHODS: The Traditional
      Chinese Medicine Health Self-Evaluation Scale (TCM-50) was developed by
      verification of dimensions, formation of item pool, verification of scoring
      methodology, and pilot test of scale and item analysis. RESULTS: TCM-50 composed
      of 50 items that could be classified into 4 dimensions including physiology and
      health, psychology and health, nature and health, and society and health. An
      examination of reliability and validity of TCM-50 yielded Cronbach's alpha
      coefficient of 0.927, and half coefficient of was 0.876. The intraclass
      correlation coefficient of total score was 0.912. After using SF-36 questionnaire
      to evaluate the criterion validity, the Pearson of the score of the two scales
      from the same participant was 0.740. CONCLUSIONS: TCM-50 has good reliability and
      validity, and can yield similar levels of efficacy as SF-36 in terms of
      evaluating people's overall health level. As a scale based on CM theory, TCM-50
      is suitable for self-measuring the general health of Chinese patients.

PMID- 25579192
TI  - Designer cell signal processing circuits for biotechnology.
AB  - Microorganisms are able to respond effectively to diverse signals from their
      environment and internal metabolism owing to their inherent sophisticated
      information processing capacity. A central aim of synthetic biology is to control
      and reprogramme the signal processing pathways within living cells so as to
      realise repurposed, beneficial applications ranging from disease diagnosis and
      environmental sensing to chemical bioproduction. To date most examples of
      synthetic biological signal processing have been built based on digital
      information flow, though analogue computing is being developed to cope with more
      complex operations and larger sets of variables. Great progress has been made in
      expanding the categories of characterised biological components that can be used
      for cellular signal manipulation, thereby allowing synthetic biologists to more
      rationally programme increasingly complex behaviours into living cells. Here we
      present a current overview of the components and strategies that exist for
      designer cell signal processing and decision making, discuss how these have been
      implemented in prototype systems for therapeutic, environmental, and industrial
      biotechnological applications, and examine emerging challenges in this promising
      field. 

PMID- 25579200
TI  - Encapsulation of an f-block metal atom/ion to enhance the stability of C20 with
      the I(h) symmetry.
AB  - Based on the density functional theory, the geometric and electronic structures,
      chemical stability, and bonding properties of the endohedral metallofullerenes,
      M@C20 (M = Eu(3-), Am(3-), Gd(2-), Cm(2-), Tb(-), Bk(-), Dy, Cf, Ho(+), Es(+),
      Er(2+), Fm(2+), Tm(3+), Md(3+), Yb(4+), No(4+), Lu(5+), and Lr(5+)), were
      investigated. Through encapsulation of an f-block metal atom/ion with 12 valence
      electrons, the bare C20 cage with the D2h point group could be stabilized to a
      highly symmetrical Ih structure. The calculated values of HOMO-LUMO energy gaps
      using the B3lYP and BHHLYP functionals ranged from 2.22 to 5.39 eV and from 3.89
      to 7.95 eV, respectively. The stability of these metal-encapsulated clusters can
      be attributed to the 32-electron rule, where the central metal atom's orbitals
      strongly participated in the t2u, gu, t1u, hg, and ag valence molecular orbitals.

PMID- 25579196
TI  - Wrist-ankle acupuncture and ginger moxibustion for preventing gastrointestinal
      reactions to chemotherapy: A randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effects of wrist-ankle acupuncture combined with
      ginger moxibustion against gastrointestinal tract reactions (nausea, vomiting,
      and constipation) to chemotherapy in cancer patients. METHODS: A total of 60
      patients with gynecological tumors treated by chemotherapy were randomly divided
      into two groups. The treatment group (30 cases) underwent wrist-ankle acupuncture
      and ginger moxibustion, whereas tropisetron hydrochloride and dexamethasone were
      intravenously administered to the control group (30 cases) during chemotherapy.
      RESULTS: The frequency of nausea in the treatment group was significantly less
      than that of the control group from the 2nd to the 5th day of chemotherapy
      (P<0.01). The anti-emetic effect in the treatment group was significantly better
      than that in the control group on the 3rd day of therapy (P<0.05). The incidence
      rate of constipation was significantly lower in the treatment group than that in
      the control group (P<0.01). Furthermore, the cost of therapy for the treatment
      group was significantly lower than that of the control group (P<0.01). Only 1
      patient manifested a post-acupuncture side effect in the form of subcutaneous
      blood stasis. CONCLUSION: Wrist-ankle acupuncture combined with ginger
      moxibustion could prevent gastrointestinal tract reactions to chemotherapy in
      cancer patients. In addition, the proposed method had fewer side effects, lower
      cost, and less risk.

PMID- 25579201
TI  - Identifying effective techniques within psychological treatments for irritable
      bowel syndrome: a meta-analysis.
AB  - OBJECTIVES: Psychological interventions can alleviate the symptoms of irritable
      bowel syndrome (IBS) and psychological distress commonly reported among IBS
      sufferers. However, the theoretical underpinnings and intervention techniques
      used by such interventions vary considerably. This study aimed to identify which
      theoretical approaches and techniques lead to greater improvements in IBS
      symptoms and psychological well-being within psychological interventions for IBS.
      METHODS: Outcome data were extracted from 48 randomized controlled trials testing
      psychological treatments for IBS. Theoretical intervention targets and
      intervention techniques of each study were identified. Cumulative effect sizes
      were calculated for pain, bowel dysfunction, composite symptom scores,
      psychological distress, and health-related quality of life. Comparative analyses
      contrasted the effect sizes of studies which included each intervention technique
      to those which did not. RESULTS: Cumulatively, interventions significantly
      improved all outcomes, with effect sizes (Hedges' g) ranging from 0.32 to 0.64.
      Interventions which stated a theoretical intervention target, prompted self
      monitoring of symptoms and cognitions, provided tailored feedback linking
      symptoms and cognitions, utilized problem solving or assertiveness training and
      provided general support had greater effects upon symptom and well-being outcomes
      than interventions which did not (all P<.05). Across all studies, improvements in
      psychological distress were associated with improvements in composite symptom
      scores (P<.01). CONCLUSIONS: This study identifies a set of techniques associated
      with improvements in IBS symptoms and psychological well-being in existing
      interventions, and provides initial evidence for the link between improvements in
      psychological distress and IBS composite symptom scores. These findings can aid
      the development and refinement of psychological treatments for IBS.

PMID- 25579202
TI  - Effects of salting-in interactions on macromolecule diffusiophoresis and salt
      osmotic diffusion.
AB  - Macromolecule diffusiophoresis (i.e., macromolecule migration induced by a salt
      concentration gradient) in water and salt osmotic diffusion (i.e., salt migration
      induced by a macromolecule concentration gradient) are two cross-diffusion
      mechanisms caused by macromolecule-salt interactions. We investigated the effect
      of salting-in interactions on the behavior of these two cross-diffusion
      mechanisms. Our results are distinct from those previously obtained in the case
      of salting-out interactions. Cross-diffusion was experimentally characterized by
      Rayleigh interferometry at 25  degrees C. Specifically, multicomponent diffusion
      coefficients were measured for a neutral polymer, polyethylene glycol (molar
      mass, 20 kg/mol), in aqueous solutions of three thiocyanate salts (NaSCN, KSCN,
      and NH4SCN) as a function of salt concentration at low polymer concentration
      (0.5% w/w). Our results on salt osmotic diffusion, which were qualitatively
      different from those previously obtained for salting-out salts, were used to
      quantitatively characterize the strength of salting-in interactions. The behavior
      of polymer diffusiophoresis as a function of salt concentration and cation type
      reveals that polymer chains have an extrinsic negative charge, consistent with
      anion binding being the cause of salting-in interactions. To quantitatively
      examine the effect of anion binding on salt osmotic diffusion and polymer
      diffusiophoresis, we developed a theoretical model based on the linear laws of
      nonequilibrium thermodynamics for diffusion, the Scatchard binding model, and
      particle electrophoresis. This work contributes to the understanding of the
      multifaceted effects of molecular interactions on cross-diffusion mechanisms,
      salting-in interactions, and the Hofmeister series.

PMID- 25579204
TI  - Subforaminal bridges in Hymenoptera (Insecta), with a focus on Chalcidoidea.
AB  - Variation in structures of the posterior surface of the head in Hymenoptera is
      compared and interpreted according to theories of head capsule evolution, with
      focus on understanding previously baffling conditions in the superfamily
      Chalcidoidea. Features are investigated separately without first classifying
      subforaminal bridges into subcategories. In Proctotrupomorpha (including
      Chalcidoidea), Ceraphronoidea and some Ichneumonoidea, there are multiple
      posterior pits associated with the tentorium. In most examined Hymenoptera with a
      subforaminal bridge, there was a differentiated median area, typically with
      highly variable microtrichia. This area is elevated in Cephoidea and
      Pamphilioidea, but is not elevated in other Hymenoptera. Subforaminal bridges in
      Apocrita previously classified as hypostomal bridges are discussed in the context
      of A.P. Rasnitsyn's hypothesis that relative importance of adult feeding drives
      subforaminal bridge evolution. 

PMID- 25579205
TI  - Embryonic development of a collembolan, Tomocerus cuspidatus Borner, 1909: with
      special reference to the development and developmental potential of serosa
      (Hexapoda: Collembola, Tomoceridae).
AB  - The embryogenesis of a collembolan, Tomocerus cuspidatus, was examined and
      described, with special reference to the development of serosa and its
      developmental potential. As a result of cleavage, which starts with holoblastic
      cleavage and changes to the superficial type, the blastoderm forms. At the center
      of the dorsal side of the egg, the primary dorsal organ develops. The mesoderm is
      segregated beneath the entire blastoderm, excluding the primary dorsal organ. The
      mesoderm then migrates to the presumptive embryonic area, and the embryonic and
      extra-embryonic areas differentiate. The area lined with mesoderm is the embryo,
      and that devoid of it is the serosa. Owing to blastokinesis completion, the extra
      embryonic area or the serosa is highly stretched, and the serosal cells are often
      found to undergo mitosis. The serosa possesses the ability to differentiate into
      the body wall. It was confirmed, in contrast to the previous understanding, that
      the serosal cells do not degenerate, but participate in the formation of the body
      wall or definitive dorsal closure. Integrating this newly obtained information
      and other embryological evidence, the basal splitting of Hexapoda was
      phylogenetically discussed and reconstructed, and a phylogeny formulated as
      "Ellipura (=Protura+Collembola)+Cercophora (=Diplura and Ectognatha)" was
      proposed.

PMID- 25579206
TI  - Overcoming the concentration-dependence of responsive probes for magnetic
      resonance imaging.
AB  - In magnetic resonance imaging, contrast agents are molecules that increase the
      contrast-to-noise ratio of non-invasively acquired images. The information gained
      from magnetic resonance imaging can be increased using responsive contrast agents
      that undergo chemical changes, and consequently changes to contrast enhancement,
      for example in response to specific biomarkers that are indicative of diseases. A
      major limitation with modern responsive contrast agents is concentration
      dependence that requires the concentration of contrast agent to be known: an
      extremely challenging task in vivo. Here, we review advances in several
      strategies aimed at overcoming the concentration-dependent nature of responsive
      contrast agents. 

PMID- 25579208
TI  - DNA double-strand break repair inhibitors as cancer therapeutics.
AB  - Among DNA damages, double-strand breaks (DSBs) are one of the most harmful
      lesions to a cell. Failure in DSB repair could lead to genomic instability and
      cancer. Homologous recombination (HR) and nonhomologous end joining (NHEJ) are
      major DSB repair pathways in higher eukaryotes. It is known that expression of
      DSB repair genes is altered in various cancers. Activation of DSB repair genes is
      one of the reasons for chemo- and radioresistance. Therefore, targeting DSB
      repair is an attractive strategy to eliminate cancer. Besides, therapeutic agents
      introduce breaks in the genome as an intermediate. Therefore, blocking the
      residual repair using inhibitors can potentiate the efficacy of cancer treatment.
      In this review, we discuss the importance of targeting DSB repair pathways for
      the treatment of cancer. Recent advances in the development of DSB repair
      inhibitors and their clinical relevance are also addressed.

PMID- 25579207
TI  - Detection of intestinal cancer by local, topical application of a quenched
      fluorescence probe for cysteine cathepsins.
AB  - Early detection of colonic polyps can prevent up to 90% of colorectal cancer
      deaths. Conventional colonoscopy readily detects the majority of premalignant
      lesions, which exhibit raised morphology. However, lesions that are flat and
      depressed are often undetected using this method. Therefore, there is a need for
      molecular-based contrast agents to improve detection rates over conventional
      colonoscopy. We evaluated a quenched fluorescent activity-based probe (qABP;
      BMV109) that targets multiple cysteine cathepsins that are overexpressed in
      intestinal dysplasia in a genetic model of spontaneous intestinal polyp formation
      and in a chemically induced model of colorectal carcinoma. We found that the qABP
      selectively targets cysteine cathepsins, resulting in high sensitivity and
      specificity for intestinal tumors in mice and humans. Additionally, the qABP can
      be administered by either intravenous injection or by local delivery to the
      colon, making it a highly valuable tool for improved detection of colorectal
      lesions using fluorescence-guided colonoscopy. 

PMID- 25579210
TI  - [Textual research of scabies in the Warring States and Qin-Han Dynasties].
AB  - Scabies, a kind of skin disease frequently seen in the period of Warring States
      and Qin-Han Dynasties. By investigating the epidemic condition, disease title,
      recognition on the disease and the prevention and its treatment through the
      textual documents, unearthed texts, and dictionaries of this period, it can be
      seen that "scabies" refers to the itching and corrugation of skin. It was also
      called "jia" (scar) and belonged to the "dry itching"disease. At that time,
      people also knew the seasonal, and geographical rules of its incidence and its
      pathogenic agent, the scabies parasite (sacoptic mite). Treatments included hot
      compress, rubbing, bathing, and internal medications, mostly inherited in later
      generations. 

PMID- 25579211
TI  - [Sman pa grwa tshang and the development of Tibetan Medicine].
AB  - Sman pa grwa tshang refers to Tibetan medical schools attached to Tibetan
      Buddhist monasteries (basically of the Gelugpa sect), which is a comprehensive
      institution devoted to medical education, clinic treatment and medicinal
      production. It has played a significant role in the training of medical
      professionals, and is itself an embodiment and outgrowth of the further
      institutionalization and systematization of the monastery educational system
      after the establishment of Gelugpa sect in the 15(th) century. The model of Sman
      pa grwa tshang first took shape from the famous Chagpori Grophangling,
      established in Lhasa by Desi Sanggy Gyamtso (Tib: Sde srid sangs rgyas rgya mtso
      1653-1705) in 1696. Later, the model spread to Amdo, Mongolian areas and China's
      cities like Beijing and Chengde where almost a hundred Sman pa grwa tshangs were
      set up successively. The emergence of Sman pa grwa tshangs played a significant
      role in the transmission and development of Tibetan medicine. 

PMID- 25579209
TI  - Identifying drug-target selectivity of small-molecule CRM1/XPO1 inhibitors by
      CRISPR/Cas9 genome editing.
AB  - Validation of drug-target interaction is essential in drug discovery and
      development. The ultimate proof for drug-target validation requires the
      introduction of mutations that confer resistance in cells, an approach that is
      not straightforward in mammalian cells. Using CRISPR/Cas9 genome editing, we show
      that a homozygous genomic C528S mutation in the XPO1 gene confers cells with
      resistance to selinexor (KPT-330). Selinexor is an orally bioavailable inhibitor
      of exportin-1 (CRM1/XPO1) with potent anticancer activity and is currently under
      evaluation in human clinical trials. Mutant cells were resistant to the induction
      of cytotoxicity, apoptosis, cell cycle arrest, and inhibition of XPO1 function,
      including direct binding of the drug to XPO1. These results validate XPO1 as the
      prime target of selinexor in cells and identify the selectivity of this drug
      toward the cysteine 528 residue of XPO1. Our findings demonstrate that
      CRISPR/Cas9 genome editing enables drug-target validation and drug-target
      selectivity studies in cancer cells.

PMID- 25579212
TI  - [Gender, medicine and consumer culture: the cultural history of comb in the Ming
      and Qing Dynasties].
AB  - In the Ming and Qing Dynasties, in addition to combing the hair, the comb also
      gradually played a role in people's daily life for disease treatment and keeping
      people's health. In short, during this period, the characteristic of comb reveal,
      as a whole, its reinforcing practicability and weakening of its ornamentality.
      During its application, people's behavioral activities endowed the comb with
      definite cultural connotation, which, thanks to the presence of gender and
      personality, became the symbol for expressing love between man and woman. By
      analogizing people's thought, since the comb could dredge something. Therefore,
      it can be used to cure diseases. Thus, it could be seen that, based on consumer's
      cultural description, the comb, tiny as it may be, did reflect the aesthetic
      ideas and interests and daily life-preservation habit of the literati due to the
      flourishing of book market in the Ming and Qing Dynasties. 

PMID- 25579213
TI  - [An exploration of the training of medical talents in China for Ryukyu islands
      based on the Liu qiu bai wen (One Hundred Question of Ryukyu)].
AB  - Ryukyu sent more than 20 batches of returned students to China for studying
      during the Ming and Qing Dynasties, many of whom were studying medicine. Liu qiu
      bai wen (One Hundred Question of Ryukyu) was the record of discussion between Cao
      Cunxin, a famous doctor of the Qing Dynasty, and the oversea disciples of Lu
      Fengyi from Ryukyu. However, it was not only a medical book, but also served as
      an important witness on overseas dissemination of TCM, and the fresh case of
      Chinese training medical talented persons for Ryukyu. Training Ryukyu medical
      students in the Qing Dynasty was good for the expansion of Chinese medicine in
      the Ryukyu, and promoted the development and social progress of the Ryukyu
      medicine and health, made a significant contribution to maintain the friendly
      relationship between the two countries. 

PMID- 25579214
TI  - [Xi yuan lu (Records for Washing Away of Wrong Cases) and justice tests in the
      Republic of China in the context of western knowledge].
AB  - Xi yuan lu (Records for Washing Away of Wrong Cases) has become the important
      criterion and authority of the criminal justice tests in the proceedings of case
      and judicatory judgment, since it was issued royally and officially in the reign
      of Kangxi Emperor of the Qing Dynasty. However, the Xi yuan lu and its
      traditional tests was subjected to strong criticism after the introduction of
      modern science. Especially since the May 4(th) New Culture Movement, not only the
      theory in the Xi yuan lu had been met with incredulity and condemned sharply
      through western chemical tests by the intelligentsia, but also the traditional
      methods of justice tests based on the book was fully criticized. Though the Xi
      yuan lu has fallen down from the altar, the traditional methods in the book still
      were used in practice in China during 1930s--1940s because the scientific system
      of forensic medicine was not established yet. Xi yuan lu, though fallen yet not
      defeated, reveals its deep-rooted life. The modern fate of the Xi yuan lu was not
      only the direct result of different historical conversation in the different
      periods of modern time, but also a true picture of modern China.

PMID- 25579215
TI  - [Alzheimer and the discovery of Alzheimer's disease].
AB  - Alzheimer was born in Germany in 1864. In 1887, Alzheimer graduated with a
      medical doctor degree at the University of Wurzburg. In 1888, Alzheimer began to
      work in the Community Hospital for Mental and Epileptic Patients in Frankfurt am
      Main for 14 years. During this time, Alzheimer published the six-volume
      Histologic and Histopathologic Studies of the Cerebral Cortex, with co-author
      Franz Nissl. In 1903, Alzheimer came to work in the Royal Psychiatric Clinic of
      the University of Munich. One year later, he published his postdoctoral paper of
      Histological Studies about the Differential Diagnosis of Progressive Paralysis in
      1904. In 1912, Alzheimer was provided the chair of psychiatry at the University
      of Breslau. On the way to Breslau, Alzheimer got sick, and eventually died in
      1915. In 1906, Alzheimer found numerous amyloid plaques and neurofibrillary
      tangles in the brain of a patient called Auguste under the microscope. In
      November of the same year, Alzheimer gave a lecture about Auguste's case at the
      37(th) Conference of South-West German Psychiatrists in Tubingen, which received
      little attention. In 1910, Kraepelin mentioned "Alzheimer's disease" for the
      first time to name the disease of what Auguste got in the 8th edition of Handbook
      of Psychiatry. Therefore, Alzheimer achieved worldwide recognition. 

PMID- 25579216
TI  - [Comparative study of theoretical literature on cold pathogenic disease in Wai
      tai mi yao fang (Arcane Essentials from the Imperial Library) and Tai ping sheng
      hui fang (Taiping Holy Prescriptions for Universal Relief)].
AB  - In the Wai tai mi yao fang (Arcane Essentials from the Imperial Library) compiled
      in 752, its portion on cold pathogenic disorders embodies the achievements before
      the mid Tang Dynasty, whereas that in the Tai ping sheng hui fang (Taiping Holy
      Prescriptions for Universal Relief), compiled in 992 embodies those before the
      early Song Dynasty. Comparison on the theory of cold disorders in both books
      reveal that, during the 2 centuries period from mid Tang to early Song Dynasties,
      the texts as a carrier for the transmission of such theory in both show no
      distinct changes, but only with minor revisions and improvements. 

PMID- 25579217
TI  - [The version and academic characteristics of Mai jue kan wu (Correcting Errors in
      Pulse Study in Verse)].
AB  - Mai jue kan wu (Correcting Errors in Pulse Study in Verse) was written by Dai
      Qizong of the Yuan Dynasty without block-printing when completed. It was reviewed
      and checked by Wang Ji, attached with the main discourses on pulse taking from
      various scholars of pulse taking and Jiao shi huo mai lun (On Pulse-taking with
      Corrections on Its Popular Difficult Issues) and was block-printed in 1523. This
      book corrects the fallacies on the descriptions of pulse shape and pulse body
      reflecting its underlying diseases appeared in Mai jue (Pulse Study in Verse),
      refutes its classification of the so-called "Seven exterior", "Eight interior"
      and "Nine dao (channels)". It also creates the measures for the studies of pulse
      taking, including "differentiating, combining, doubling, comparing and
      classifying". 

PMID- 25579218
TI  - [Analysis of images in Japanese book Fukusho-Kiran (Medical Book Focusing on
      Abdominal Palpation) and Fukusho-Kiran yoku (Supplement to Medical Book Focusing
      on Abdominal Palpation)].
AB  - Hukusyo-kiran (Medical Book Focusing on Abdominal Palpation) and Hukusyo-kiran
      yoku (Supplement to Medical Book Focusing on Abdominal Palpation) are two typical
      monographs of Fukushin (abdominal palpation), with a total of 148 images about
      abdominal palpation. These images can be divided into 5 kinds: locations,
      theories, techniques, diseases and medicines, with its own system covering the
      theories, principles, prescriptions and medicines of abdominal palpation. It can
      be used as a guide for clinicians to differentiate the locations and qualities of
      diseases, confirm the principles of treatment, guide the usage of medicines, and
      predict the prognosis, with the rather high theoretic and academic value,
      deserving further research and analysis for the modern scholars. 

PMID- 25579219
TI  - Comparative real-time study of cellular uptake of a formulated conjugated
      linolenic acid rich nano and conventional macro emulsions and their bioactivity
      in ex vivo models for parenteral applications.
AB  - The objective of the present study was to fabricate and monitor real-time, impact
      of a stable conjugated linolenic acid, alpha-eleostearic acid (ESA) rich
      nanoemulsion (NE) formulation (d < 200 nm) vis-a-vis ESA conventional emulsion
      (CE) system in ex vivo systems against both endogenous and exogenous reactive
      oxygen species (ROS). Accordingly, stable nanoemulsion formulation of ESA was
      engineered with the aid of bitter melon seed oil and non-toxic excipients.
      Morphology and particle size of the emulsion formulations were studied to
      validate stability. The real-time rapid uptake of the ESA NE and its increased
      prophylactic efficacy against induced endogenous and exogenous ROS in terms of
      cell viability and membrane integrity was evaluated flow-cytometrically and with
      fluorescence microscopic analysis of different primary cells. It was found that
      the fabricated non-toxic ESA NE had stable parameters (hydrodynamic mean
      diameter, particle size distribution and zeta potential) for over 12 weeks.
      Further, ESA NE at a concentration of ~ 70 MUM exhibited maximum efficacy in
      protecting cells from oxidative damage against both endogenous and exogenous ROS
      in lymphocytes and hepatocytes as compared to its corresponding presence in the
      CE formulation. This study provides a real-time empirical evidence on the
      influence of nano formulation in enhancing bioavailability and antioxidative
      properties of ESA.

PMID- 25579220
TI  - Novel basic helix-loop-helix transcription factor hes4 antagonizes the function
      of twist-1 to regulate lineage commitment of bone marrow stromal/stem cells.
AB  - Basic helix-loop-helix (bHLH) transcription factors are pivotal regulators of
      cellular differentiation and development. The bHLH factor, Twist-1 has previously
      been found to control bone marrow stromal/stem cells (BMSC) self-renewal, life
      span, and differentiation, however not much is known about its mechanism of
      action. In this study, we have discovered a novel Twist-1 regulated bHLH gene,
      Hes4, expressed in humans, but not in mice. Its closest homologue in both humans
      and mice is Hes1. Overexpression and knockdown studies demonstrated that Hes4
      promotes osteogenesis resulting in an increase in Runx2, osteocalcin,
      osteopontin, and bone sialoprotein expression. Conversely, Hes4 was found to
      inhibit adipogenesis accompanied by a decrease in PPARgamma2, adiponectin, and
      adipsin expression. In vitro studies indicate that Hes4 employs a mechanism to
      counteract the negative function of Twist-1 on osteogenesis by binding to Twist-1
      and inhibiting the ability of Twist-1 to bind and inhibit Runx2. In vivo
      chromatin immunoprecipitation and in vitro reporter assays illustrated that Runx2
      recruitment to the osterix promoter, was found to be enhanced in the presence of
      Hes4 and inhibited in the presence of Twist-1. Therefore, Hes4 antagonizes the
      function of Twist-1 to regulate lineage commitment of BMSC. These studies
      highlight the potential differences in molecular mechanisms that regulate BMSC
      osteogenic differentiation between human and mouse. 

PMID- 25579221
TI  - Health promotion messages: the role of social presence for food choices.
AB  - We investigated whether social presence cues encourage consumers to self-regulate
      and select healthier food products. In the first experiment, workers completed
      food choices in an e-commerce environment. After the activation of health-related
      goals, they saw a social presence cue and were asked to choose between healthy
      and unhealthy food options. The analyses revealed main effects of social presence
      and health goal activation on food choices. These effects were additive, such
      that the combination of social presence and health goals induced significantly
      healthier choices compared with the control group. The second experiment further
      examined social presence cues that were presented on a menu. The results showed
      significant effects on food choices and on the perceived self-regulatory success
      in dieting. These findings indicate that social presence cues could be employed
      to increase healthful eating and, furthermore, that it may be useful to co
      activate multiple cues in health promotion messages. 

PMID- 25579222
TI  - Stimulus control and affect in dietary behaviours. An intensive longitudinal
      study.
AB  - BACKGROUND: Dietary behaviours are substantially influenced by environmental and
      internal stimuli, such as mood, social situation, and food availability. However,
      little is known about the role of stimulus control for eating in non-clinical
      populations, and no studies so far have looked at eating and drinking behaviour
      simultaneously. METHOD: 53 individuals from the general population took part in
      an intensive longitudinal study with repeated, real-time assessments of eating
      and drinking using Ecological Momentary Assessment. Eating was assessed as main
      meals and snacks, drinks assessments were separated along alcoholic and non
      alcoholic drinks. Situational and internal stimuli were assessed during both
      eating and drinking events, and during randomly selected non-eating occasions.
      Hierarchical multinomial logistic random effects models were used to analyse
      data, comparing dietary events to non-eating occasions. RESULTS: Several
      situational and affective antecedents of dietary behaviours could be identified.
      Meals were significantly associated with having food available and observing
      others eat. Snacking was associated with negative affect, having food available,
      and observing others eat. Engaging in activities and being with others decreased
      the likelihood of eating behaviours. Non-alcoholic drinks were associated with
      observing others eat, and less activities and company. Alcoholic drinks were
      associated with less negative affect and arousal, and with observing others eat.
      CONCLUSIONS: RESULTS support the role of stimulus control in dietary behaviours,
      with support for both internal and external, in particular availability and
      social stimuli. The findings for negative affect support the idea of comfort
      eating, and results point to the formation of eating habits via cue-behaviour
      associations.

PMID- 25579228
TI  - Contributions to activity enhancement via Fe incorporation in Ni
      (oxy)hydroxide/borate catalysts for near-neutral pH oxygen evolution.
AB  - Ni-borate materials are oxygen evolution catalysts that operate at near-neutral
      pH and have been found previously to improve due to structural changes induced
      via anodic conditioning. We find that this increased activity after conditioning
      at 0.856 V vs. SCE, as measured on a turn-over frequency basis (TOF) at 400 mV
      overpotential (TOF = 0.38 s(-1)), accompanies significant Fe incorporation (14%).
      Films conditioned in Fe-free electrolyte exhibit ~10 times lower activity (TOF =
      0.03 s(-1)). By co-depositing Fe-Ni we demonstrate high activity without
      conditioning (TOF = 0.24 s(-1)) which improves further with shortened (~30 min)
      conditioning (TOF = 1.4 s(-1)). 

PMID- 25579226
TI  - Release of mitochondrial Opa1 following oxidative stress in HT22 cells.
AB  - Cellular mechanisms involved in multiple neurodegenerative diseases converge on
      mitochondria to induce overproduction of reactive oxygen species, damage to
      mitochondria, and subsequent cytochrome c release. Little is currently known
      regarding the contribution mitochondrial dynamics play in cytochrome c release
      following oxidative stress in neurodegenerative disease. Here we induced
      oxidative stress in the HT22 cell line with glutamate and investigated key
      mediators of mitochondrial dynamics to determine the role this process may play
      in oxidative stress induced neuronal death. We report that glutamate treatment in
      HT22 cells induces increase in reactive oxygen species (ROS), release of the
      mitochondrial fusion protein Opa1 into the cytosol, with concomitant release of
      cytochrome c. Furthermore, following the glutamate treatment alterations in cell
      signaling coincide with mitochondrial fragmentation which culminates in
      significant cell death in HT22 cells. Finally, we report that treatment with the
      antioxidant tocopherol attenuates glutamate induced-ROS increase, release of
      mitochondrial Opa1 and cytochrome c, and prevents cell death. 

PMID- 25579227
TI  - Using cross-classified multilevel models to disentangle school and neighborhood
      effects: an example focusing on smoking behaviors among adolescents in the United
      States.
AB  - BACKGROUND: Despite much interest in understanding the influence of contexts on
      health, most research has focused on one context at a time, ignoring the reality
      that individuals have simultaneous memberships in multiple settings. METHOD:
      Using the example of smoking behavior among adolescents in the National
      Longitudinal Study of Adolescent Health, we applied cross-classified multilevel
      modeling (CCMM) to examine fixed and random effects for schools and
      neighborhoods. We compared the CCMM results with those obtained from a
      traditional multilevel model (MLM) focused on either the school and neighborhood
      separately. RESULTS: In the MLMs, 5.2% of the variation in smoking was due to
      differences between neighborhoods (when schools were ignored) and 6.3% of the
      variation in smoking was due to differences between schools (when neighborhoods
      were ignored). However in the CCMM examining neighborhood and school variation
      simultaneously, the neighborhood-level variation was reduced to 0.4%. CONCLUSION:
      Results suggest that using MLM, instead of CCMM, could lead to overestimating the
      importance of certain contexts and could ultimately lead to targeting
      interventions or policies to the wrong settings.

PMID- 25579229
TI  - Microbial community and removal of nitrogen via the addition of a carrier in a
      pilot-scale duckweed-based wastewater treatment system.
AB  - Carriers were added to a pilot-scale duckweed-based (Lemna japonica 0223)
      wastewater treatment system to immobilize and enhance microorganisms. This system
      and another parallel duckweed system without carriers were operated for 1.5
      years. The results indicated the addition of the carrier did not significantly
      affect the growth and composition of duckweed, the recovery of total nitrogen
      (TN), total phosphorus (TP) and CO2 or the removal of TP. However, it
      significantly improved the removal efficiency of TN and NH4(+)-N (by 19.97% and
      15.02%, respectively). The use of 454 pyrosequencing revealed large differences
      of the microbial communities between the different components within a system and
      similarities within the same components between the two systems. The carrier
      biofilm had the highest bacterial diversity and relative abundance of nitrifying
      bacteria (3%) and denitrifying bacteria (24% of Rhodocyclaceae), which improved
      nitrogen removal of the system. An efficient N-removal duckweed system with
      enhanced microorganisms was established.

PMID- 25579230
TI  - Lipid extracted algae as a source for protein and reduced sugar: a step closer to
      the biorefinery.
AB  - The objective of this study was to investigate the feasibility of using lipid
      extracted algae (LEA) as a source for protein and reduced sugar, and the effects
      of various procedural treatments on their yields. LEA provided comparable yields
      of protein and reduced sugars to those from total algae. Oven drying provided
      highest yields of all products followed by freeze drying, while sun drying
      significantly lowered their yields. Effective cell disruption by microwave and
      autoclave increased the lipid yields from algae, but resulted in increased loss
      of other compounds with lipid extracting solvents lowering their yields during
      sequential extraction. Relatively inefficient cell disruption by ultrasonication
      and osmotic shock lowered the amount of cell protein lost to the lipid extracting
      solvents. These results highlight the complexity of concurrent extraction of all
      value added products from algae, and the need for proper selection of the
      processes to achieve the objectives of integrated biorefinery. 

PMID- 25579231
TI  - Enhanced biofuel production potential with nutritional stress amelioration
      through optimization of carbon source and light intensity in Scenedesmus sp. CCNM
      1077.
AB  - Microalgal mixotrophic cultivation is one of the most potential ways to enhance
      biomass and biofuel production. In the present study, first of all ability of
      microalgae Scenedesmus sp. CCNM 1077 to utilize various carbon sources under
      mixotrophic growth condition was evaluated followed by optimization of glucose
      concentration and light intensity to obtain higher biomass, lipid and
      carbohydrate contents. Under optimized condition i.e. 4 g/L glucose and 150 MUmol
      m(-2) s(-1) light intensity, Scenedesmus sp. CCNM 1077 produced 1.2g/L dry cell
      weight containing 23.62% total lipid and 42.68% carbohydrate. Addition of glucose
      shown nutritional stress ameliorating effects and around 70% carbohydrate and 25%
      total lipid content was found with only 21% reduction in dry cell weight under
      nitrogen starved condition. This study shows potential application of
      mixotrophically grown Scenedesmus sp. CCNM 1077 for bioethanol and biodiesel
      production feed stock.

PMID- 25579233
TI  - Obesity and menopause.
AB  - Over the recent decades, the prevalence of obesity in the United States has
      increased to epidemic proportions to more than 35% of adults, along with an
      increased risk of a number of health conditions, including hypertension, adverse
      lipid concentrations, and type 2 diabetes. The relationships between menopausal
      transition, weight gain, and obesity are reported but incompletely understood.
      The association between menopause and these measures has been the subject of many
      studies, along with examining their effect on reproductive hormones and
      menopausal symptoms. The purpose of this review is to summarize what is published
      in the literature on this subject and examine it through: (1) the possible impact
      of obesity on the timing of menopause; (2) the effect of obesity on menopausal
      symptoms and reproductive hormones around the time of menopause; and (3) the
      effect of menopause on obesity, weight gain, and body composition. 

PMID- 25579232
TI  - Susceptibility to measles, mumps, and rubella in 5-year-old children in Flanders,
      Belgium.
AB  - The second dose of an MMR vaccine is a catch up for persons who did not receive
      the first dose or for primary vaccine failures. Catch up doses can be scheduled
      according to convenience into the program of the country. The second MMR dose is
      often administered at the age of 5 years, before school entry. Some countries
      chose to implement the second dose at the age of 10-13 years, as is the case for
      Belgium. The here presented long-term follow-up of a cohort of children, set up
      originally to analyze maternal antibodies against vaccine preventable diseases,
      offers a unique opportunity to evaluate ad interim the current long-interval MMR
      vaccination schedule in Belgium. After 1 MMR dose at 12 months of age, rubella
      immunity is almost intact at 5 years of age (94.5 % is seropositive), measles
      seropositivity scores 86.8 %, and mumps 32 %, measured with ELISA. A
      seroneutralization (SN) test for mumps antibodies reveals much higher
      seropositivity rates (88 %). Using a regression model on the log (IgG) titer for
      all antigens, no influence was found from any of the studied variables, except
      for girls who had a significantly higher rubella IgG titer (p=0.002) compared to
      boys. CONCLUSION: The data show considerable susceptibility to mumps and measles
      in 5-year-old children, confirming a previously conducted seroprevalence study
      (2006). Both advantages and disadvantages of shortening or enlarging the vaccine
      schedule are discussed.

PMID- 25579234
TI  - Extracellular dopamine and alterations on dopamine transporter are related to
      reserpine toxicity in Caenorhabditis elegans.
AB  - Reserpine is used as an animal model of parkinsonism. We hypothesized that the
      involuntary movements induced by reserpine in rodents are induced by dopaminergic
      toxicity caused by extracellular dopamine accumulation. The present study tested
      the effects of reserpine on the dopaminergic system in Caenorhabditis elegans.
      Reserpine was toxic to worms (decreased the survival, food intake, development
      and changed egg laying and defecation cycles). In addition, reserpine increased
      the worms' locomotor rate on food and decreased dopamine levels. Morphological
      evaluations of dopaminergic CEP neurons confirmed neurodegeneration characterized
      by decreased fluorescence intensity and the number of worms with intact CEP
      neurons, and increased number of shrunken somas per worm. These effects were
      unrelated to reserpine's effect on decreased expression of the dopamine
      transporter, dat-1. Interestingly, the locomotor rate on food and the
      neurodegenerative parameters fully recovered to basal conditions upon reserpine
      withdrawal. Furthermore, reserpine decreased survival in vesicular monoamine
      transporter and dat-1 loss-of-function mutant worms. In addition, worms pre
      exposed to dopamine followed by exposure to reserpine had decreased survival.
      Reserpine activated gst-4, which controls a phase II detoxification enzymes
      downstream of nuclear factor (erythroid-derived-2)-like 2. Our findings establish
      that the dopamine transporter, dat-1, plays an important role in reserpine
      toxicity, likely by increasing extracellular dopamine concentrations. 

PMID- 25579235
TI  - [Pernicious anemia and autoimmune thyroid diseases in elderly people].
AB  - OBJECTIVE: Autoimmune thyroid diseases (ATD), and pernicious anemia (PA) in
      particular, are common in elderly people. The relationship between both of these
      is currently being discussed. The objective of this study is to determine the
      correlation between ATD and PA in elderly people, and if there are other
      associated factors affecting this relationship. MATERIAL AND METHODS: The factors
      studied to analyse this association were social-health variables, autoimmune
      comorbidity (type 1 diabetes and other autoimmune diseases), the taking of drugs
      that alter vitamin B12 levels (Metformin and protein bomb inhibitors), and the
      chronological order in which both diseases appear in this population. A logistic
      regression analysis was performed to determine which of the described variables
      could have an on both diseases. RESULTS: The prevalence was 8.2% for ATD and 3.3%
      for PA, with a progressive increase in the annual incidence in the past 10 years
      from 7.1 to 12.7 cases per 1,000 persons>65 years for ATI, and from 1.6 to 7.4
      cases for PA. PA was found in 18.6% of the patients with ATD, and the 45% of PA
      presented with ATD, mainly in women (RR=6.0). The average time in diagnosing the
      second disease was about 8 years. When there was a third autoimmune disease the
      likelihood of ATD and PA increased fourfold. Patients with ATD and consuming
      drugs which were affecting the absorption of vitamin B12 had double the
      probability of developing a PA compared with those who were not taking
      medications. CONCLUSIONS: The results of this study confirm the association
      between ATI and AP among people 65 or older, also a progressive increase in the
      incidence of these diseases.

PMID- 25579236
TI  - Retinoblastoma: might photodynamic therapy be an option?
AB  - Retinoblastoma is a tumor that mainly affects children under 5 years, all over
      the world. The origin of these tumors is related with mutations in the RB1 gene,
      which may result from genetic alterations in cells of the germ line or in retinal
      somatic cells. In developing countries, the number of retinoblastoma-related
      deaths is higher due to less access to treatment, unlike what happens in
      developed countries where survival rates are higher. However, treatments such as
      chemotherapy and radiotherapy, although quite effective in treating this type of
      cancer, do not avoid high indices of mortality due to secondary malignances which
      are quite frequent in these patients. Additionally, treatments such as
      cryotherapy, thermotherapy, thermochemotherapy, or brachytherapy represent other
      options for retinoblastoma. When all these approaches fail, enucleation is the
      last option. Photodynamic therapy might be considered as an alternative,
      particularly because of its non-mutagenic character. Photodynamic therapy is a
      treatment modality based on the administration of photosensitizing molecules that
      only upon irradiation of the tumor with a light source of appropriate wavelength
      are activated, triggering its antitumor action. This activity may be not only due
      to direct damage to tumor cells but also due to damage caused to the blood
      vessels responsible for the vascular supply of the tumor. Over the past decades,
      several in vitro and in vivo studies were conducted to assess the effectiveness
      of photodynamic therapy in the treatment of retinoblastoma, and very promising
      results were achieved.

PMID- 25579237
TI  - Formulation and evaluation of clotrimazole transdermal spray.
AB  - CONTEXT: Transdermal spray (TS) of clotrimazole (CTZ) was formulated to improve
      the drug transport through the skin up to 12 h to achieve the antifungal
      efficacy. OBJECTIVE: The aim of present study was to formulate and evaluate
      antifungal transdermal spray to improve the permeation of clotrimazole across the
      skin and to decrease the dosing frequency in fungal infection. MATERIALS AND
      METHODS: Different ratios of ethanol and acetone and various grades of eudragit
      and ethyl cellulose were evaluated according to six criteria: viscosity, drying
      time, stickiness, appearance and integrity on skin and water washability.
      Propylene glycol (PG) and polyethylene glycol 400 (PEG 400) were used in the
      study as plasticizer and solubilizer. The TS was evaluated for in vitro drug
      release, spray angle, spray pattern, average weight per dose, pH, drug content,
      evaporation time, leak test and antifungal efficacy study. RESULTS AND
      DISCUSSION: Eudragit E100 and blend of ethanol and acetone (80:20) satisfied the
      desired criteria. The selection of optimized batch was based on the results of in
      vitro drug release, spray pattern and spray angle. The optimized batch showed the
      spray angle <85 degrees  and uniform spray pattern. The formulation containing PG
      showed higher drug release than PEG 400. The inclusion of eutectic mixture
      consisting of camphor and menthol (1:1) showed improved drug transport through
      the rat skin and larger mean zone of inhibition indicating the improved
      antifungal efficacy. CONCLUSION: The TS of CTZ can be an innovative and promising
      approach for the topical administration in the fungal diseases.

PMID- 25579238
TI  - Venous sinus stenting is a valuable treatment for fulminant idiopathic
      intracranial hypertension.
AB  - Over the past 10 years, transverse sinus stenting has grown in popularity as a
      treatment for idiopathic intracranial hypertension. Although promising results
      have been demonstrated in several reported series, the vast majority of patients
      in these series have been treated on an elective basis rather than in the setting
      of fulminant disease with acute visual deterioration. We identified four patients
      who presented with severe acute vision loss between 2008 and 2012 who were
      treated with urgent transverse sinus stenting with temporary cerebrospinal fluid
      (CSF) diversion with lumbar puncture or lumbar drain as a bridge to therapy. All
      patients presented with headache, and this was stable or had improved at last
      follow-up. Three patients had improvement in some or all visual parameters
      following stenting, whereas one patient who presented with severe acute vision
      loss and optic disc pallor progressed to blindness despite successful stenting.
      We hypothesize that she presented too late in the course of the disease for
      improvement to occur. Although the management of fulminant idiopathic
      intracranial hypertension remains challenging, we believe that transverse sinus
      stenting, in conjunction with temporary CSF diversion, represents a viable
      treatment option in the acute and appropriate setting.

PMID- 25579244
TI  - Genotyping and subtyping of Giardia and Cryptosporidium isolates from commensal
      rodents in China.
AB  - Cryptosporidium and Giardia are two important zoonotic intestinal parasites
      responsible for diarrhoea in humans and other animals worldwide. Rodents, as
      reservoirs or carriers of Cryptosporidium and Giardia, are abundant and globally
      widespread. In the present study, we collected 232 fecal specimens from commensal
      rodents captured in animal farms and farm neighbourhoods in China. We collected
      33 Asian house rats, 168 brown rats and 31 house mice. 6.0% (14/232) and 8.2%
      (19/232) of these rodents were microscopy-positive for Giardia cysts and
      Cryptosporidium oocysts, respectively. All 14 Giardia isolates were identified as
      Giardia duodenalis assemblage G at a minimum of one or maximum of three gene loci
      (tpi, gdh and bg). By small subunit rRNA (SSU rRNA) gene sequencing,
      Cryptosporidium parvum (n = 12) and Cryptosporidium muris (n = 7) were
      identified. The gp60 gene encoding the 60-kDa glycoprotein was successfully
      amplified and sequenced in nine C. parvum isolates, all of which belonged to the
      IIdA15G1 subtype. Observation of the same IIdA15G1 subtype in humans (previously)
      and in rodents (here) suggests that rodents infected with Cryptosporidium have
      the potential to transmit cryptosporidiosis to humans.

PMID- 25579245
TI  - Patients with single brain metastasis from non-small cell lung cancer equally
      benefit from stereotactic radiosurgery and surgery: a systematic review.
AB  - BACKGROUND: The appropriate treatment of non-small cell lung cancer (NSCLC) with
      single brain metastasis (SBM) is still controversial. A systematic review was
      designed to evaluate the effectiveness of neurosurgery and stereotactic
      radiosurgery (SRS) in patients with SBM from NSCLC. MATERIAL/METHODS: PUBMED,
      EMBASE, the Cochrane Library, Web of Knowledge, Current Controlled Trials,
      Clinical Trials, and 2 conference websites were searched to select NSCLC patients
      with only SBM who received brain surgery or SRS. SPSS 18.0 software was used to
      analyze the mean median survival time (MST) and Stata 11.0 software was used to
      calculate the overall survival (OS). RESULTS: A total of 18 trials including 713
      patients were systematically reviewed. The MST of the patients was 12.7 months in
      surgery group and 14.85 months in SRS group, respectively. The 1, 2, and 5 years
      OS of the patients were 59%, 33%, and 19% in surgery group, and 62%, 33%, and 14%
      in SRS group, respectively. Furthermore, in the surgery group, the 1 and 3 years
      OS were 68% and 15% in patients with controlled primary tumors, and 50% and 13%
      in the other patients with uncontrolled primary tumors, respectively.
      Interestingly, the 5-year OS was up to 21% in patients with controlled primary
      tumors. CONCLUSIONS: There was no significant difference in MST or OS between
      patients treated with neurosurgery and SRS. Patients with resectable lung tumors
      and SBM may benefit from the resection of both primary lesions and metastasis.

PMID- 25579247
TI  - Prioritizing personalized medicine.

PMID- 25579246
TI  - Usefulness of antibodies and minor salivary gland biopsy in the study of sicca
      syndrome in daily clinical practice.
AB  - OBJECTIVES: To assess the association between histologic findings in the minor
      salivary gland biopsy (MSGB) and anti La (La/SS-B)y antiRo antibodies (Ro/SS-A),
      antinuclear antibodies (ANA) and Rheumatoid Factor (RF),and compare the value of
      the latter as diagnostic tests with MSGB, considered as the gold standard.
      MATERIAL AND METHOD: Patients with suspected Primary Sjogren Syndrome (PSS)
      referred for MSGB were included. Antibody measurements were performed. Grade III
      and IV biopsy results were considered positive. RESULTS: Two hundred and eighteen
      (218) patients were included, 95% females, with a median age of 54 years and 12
      months median duration of sicca symptoms. 36 of the biopsies were positive. 33%
      of patients had positive anti Ro/SS-A anti La/SS-B antibodies, 62% had positive
      ANA, and 31% positive RF. A statistically significant association was found
      between MSGB and anti Ro/SS-A anti La/SS-B, ANA and RF. ANA were the most
      sensitive antibodies (84%. 95% CI: 75- 92), and the most specific were: Anti Ro/
      SS-A and/or anti La/ SS-B (78%. 95% CI: 71-85) and RF (78%. 95% CI: 69-87).
      CONCLUSION: On PSS clinical suspicion, anti Ro/ SS-A y anti La/ SS-B antibodies
      have a great value to achieve the diagnosis, with MSGB useful for diagnosis of
      seronegative patients. The results also suggest the importance of ANA and RF for
      PSS classification.

PMID- 25579248
TI  - The efficacy of levetiracetam for focal seizures and its blood levels in
      children.
AB  - AIM: To evaluate the efficacy of levetiracetam (LEV) and the usefulness of
      measurement of its blood levels during the follow-up of patients with focal
      seizures. METHODS: Twenty-four patients (13 cases without impairment of
      consciousness or awareness and 11 cases with them or evolving to a bilateral,
      convulsive seizure) treated with LEV had their peak blood levels measured. The
      blood concentrations were measured at 2 weeks, 1 year and 2 years after reaching
      the LEV maintenance dosage. The efficacy of LEV was evaluated with repeated blood
      sampling to determine the seizure reduction rate. The patients were classified as
      effective cases (seizure reduction rate>50%) and ineffective cases (?50%).
      RESULTS: In Japanese children treated with LEV, the dosage and blood level showed
      positive correlations. The blood levels were higher in effective cases than in
      ineffective cases at all time points (p<0.05). In effective cases, the blood
      concentration was 23.26+/-6.88 MUg/mL (mean+/-SD) 2 weeks later, 23.59+/-8.23
      MUg/mL 1 year later, and 24.46+/-7.57 MUg/mL 2 years later. However, the blood
      levels and efficacies showed positive correlations only at 2 weeks and 1 year
      later. No patients had any side effects. CONCLUSIONS: No precise definition of
      the therapeutic range was possible because of the incomplete correlation between
      the blood level and seizure frequency. Instead of a therapeutic range, we
      recommend an optimal range for LEV of 20-30 MUg/mL as a therapeutic target
      without any side effects.

PMID- 25579282
TI  - The development of laryngoscopes for anaesthesia.

PMID- 25579283
TI  - Can we all survive propofol?

PMID- 25579284
TI  - Organ donation: how to increase the donor pool.

PMID- 25579285
TI  - Sugammadex: what do we know and what do we still need to know? A review of the
      recent (2013 to 2014) literature.
AB  - Since its launch in 2008, sugammadex has been considered one of the most
      significant developments in anaesthesia-related pharmacology. With almost 500
      sugammadex-related publications and over nine million patient exposures
      worldwide, user experience and scientific data have grown exponentially. However,
      several important questions are yet to be answered. This article reviews the
      sugammadex-related literature in 2013 and 2014 to determine which of these
      questions have been answered more fully over the last 18 months and which
      questions require more information and research. 

PMID- 25579286
TI  - Patient-level interventions to prevent the acquisition of resistant gram-negative
      bacteria in critically ill patients: a systematic review.
AB  - The rising incidence of multidrug-resistant Gram-negative bacterial (MDR-GNB)
      infections acquired in intensive care units has prompted a variety of patient
      level infection control efforts. However, it is not known whether these measures
      are effective in reducing colonisation and infection. The purpose of this
      systematic review was to assess the efficacy of patient-level interventions for
      the prevention of colonisation with MDR-GNB and whether these interventions are
      associated with a reduction in the rate of infection due to MDR-GNB in the
      intensive care unit. Searches were conducted on PubMed, Cochrane, EMBASE and
      World of Science databases to identify comparative interventional studies on
      patient-level interventions implemented in the intensive care unit. Literature
      published in English, Spanish or French from January 1, 2000, until April 30,
      2013, was searched. A total of 631 reports were found and we included and
      analysed 13 comparative studies that reported outcomes for an intervention
      compared with a control group. There were ten randomised and three observational
      interventional trials evaluating seven interventions. Overall, there was a
      reduction in colonisation (odds ratio [OR] 0.75; 95% confidence interval [CI]
      0.66 to 0.85) and infection (OR 0.66; 95% CI 0.59 to 0.75) with MDR-GNB. This
      trend persisted after restricting pooled analysis to randomised controlled trials
      (pooled OR 0.66; 95% CI 0.57 to 0.76 and pooled OR 0.62; 95% CI 0.54 to 0.72,
      respectively). We identified a significant reduction in MDR-GNB colonisation and
      infection through the use of patient-level interventions. This effect was mostly
      accounted for by selective digestive decontamination. However, given the
      limitations of the analysed trials, adequately powered controlled studies are
      needed to further explore the effects of patient-level interventions on
      colonisation and infection with MDR-GNB. 

PMID- 25579287
TI  - Impact of conversion from an open ward design paediatric intensive care unit
      environment to all isolated rooms environment on incidence of bloodstream
      infections and antibiotic resistance in Southern Israel (2000 to 2008).
AB  - We studied the epidemiology, microbiology, clinical aspects and outcome of
      bloodstream infections (BSI) in a tertiary paediatric intensive care unit. All
      BSI episodes were prospectively identified and analysed. The paediatric intensive
      care unit moved in 2006 from an open-plan unit to a new (all single room) unit.
      Three hundred and fifty-three BSI episodes occurred in 299 of 4162 patients.
      Overall, BSI incidence was 85 per 1000 hospitalised children. Fewer BSI episodes
      occurred during the last two years of the study (2007 to 2008), compared with
      2000 to 2006 (70 of 1061 admissions, 6.5% versus 283 of 3101 admissions, 9.1%,
      respectively, P=0.01). There were 127 of 340 (37.4%) community-acquired and 213
      of 340 (62.6%) nosocomial BSI episodes (31 of 1000 and 51 of 1000, respectively).
      Nosocomial BSI episodes decreased during 2007 to 2008 versus 2000 to 2006 (37.7%
      versus 55.8%, P=0.03). In 448 instances, pathogens were isolated, 231 (52%) Gram
      positive and 188 (42%) Gram-negative. Coagulase-negative Staphylococci, S.
      pneumoniae and S. aureus (41.1%, 19.9% and 11.7%, respectively) were the most
      common Gram-positive and Enterobacteriaceae spp. the most frequent Gram-negative
      organisms (45.2%, of them Klebsiella spp. and E. coli 40% and 29.4%,
      respectively). A significant decrease was recorded during 2007 to 2008 in
      Enterobacteriaceae resistance to piperacillin, gentamicin and ciprofloxacin.
      Thirty of 299 (10%, 9 with S. pneumoniae-BSI) patients died. A significant
      decrease in BSI and nosocomial incidence and Enterobacteriaceae spp. antibiotic
      resistance was recorded following the conversion of the paediatric intensive care
      unit from an open ward to an all isolated rooms environment. 

PMID- 25579288
TI  - Understanding Australian families' organ donation decisions.
AB  - Numbers of deceased organ donors in Australia have increased, but rates of
      consent to donation remain at around 60%. Increasing family consent is a key
      target for the Australian Organ and Tissue Authority. Reasons for donation
      decisions have been reported in the international literature, but little is known
      of reasons for Australian families' decisions. Potential organ donors in four
      Melbourne hospitals were identified and 49 participants from 40 families (23
      consenting and 17 non-consenting) were interviewed to understand reasons for
      consent decisions. Themes for consent to organ donation included that: donation
      was consistent with the deceased's explicit wishes or known values, the desire to
      help others or self-including themes of altruism, pragmatism, preventing others
      from being in the same position, consolation received from donation and aspects
      of the donation conversation and care that led families to believe donation was
      right for them. Themes for non-consent included: lack of knowledge of wishes;
      social, cultural and religious beliefs; factors related to the donation process
      and family exhaustion; and conversation factors where negative events influenced
      decisions. While reasons for consent were similar to those described in
      international literature, reasons for non-consent differed in that there was
      little emphasis on lack of trust of the medical profession, concerns regarding
      level of care provided to the potential donor, preserving the deceased's body,
      fears of body invasion or organ allocation fairness. 

PMID- 25579289
TI  - Anaesthesia priorities for Australian and New Zealand medical school curricula: a
      Delphi consensus of academic anaesthetists.
AB  - The role of anaesthetists has expanded and evolved to include critical care,
      perioperative and pain medicine and general clinical skills, as well as operating
      theatre-based clinical anaesthesia. Across Australia and New Zealand, these
      topics are taught to varying degrees, however no uniform curriculum or
      standardisation exists between universities. In this study, we used a Delphi
      technique to develop consensus-based priorities to guide medical educators when
      reviewing and implementing student anaesthesia curricula. A range of appropriate
      content has been defined, as well as details relating to duration, timing,
      teaching environment, faculty, feedback and assessment methods. Future enquiry to
      assess the efficacy of future and current teaching practices is needed to
      facilitate continued improvement. 

PMID- 25579290
TI  - Clinical predictors of a low central venous oxygen saturation after major
      surgery: a prospective prevalence study.
AB  - Optimising perioperative haemodynamic status may reduce postoperative
      complications. In this prospective prevalence study, we investigated the
      associations between standard haemodynamic parameters and a low central venous
      oxygen saturation (ScvO2) in patients after major surgery. A total of 201
      patients requiring continuous arterial and central venous pressure monitoring
      after major surgery were recruited. Simultaneous arterial and central venous
      blood gases, haemodynamic and biochemical data and perfusion index were obtained
      from patients at a single time-point within 24 hours of surgery. A low ScvO2
      (<70%) was observed in 109 patients (54%). Use of mechanical ventilation, mean
      arterial pressure, central venous pressure, haemoglobin concentrations, arterial
      pH and lactate concentrations, arterial oxygen (PaO2) and carbon dioxide tensions
      (PaCO2) were all associated with a low ScvO2 in the univariate analyses. In the
      multivariate analysis, only a higher perfusion index (odds ratio [OR] 0.87, 95%
      confidence interval [CI] 0.78 to 0.98), PaO2 (OR 0.98 per mmHg increment, 95% CI
      0.97 to 0.99) and PaCO2 (OR 0.88 per mmHg increment, 95% CI 0.82 to 0.95) and a
      lower central venous pressure (OR 1.14 per mmHg increment, 95% CI 1.04 to 1.25)
      were significantly associated with a reduced risk of a low ScvO2, all in a linear
      fashion. In conclusion, PaO2, PaCO2, perfusion index and central venous pressure
      were significant predictors of a low ScvO2 in patients after major surgery
      including cardiac surgery. 

PMID- 25579291
TI  - Complications of intra-aortic balloon pump use: does the final position of the
      IABP tip matter?
AB  - We report results of a retrospective review of intra-aortic balloon pump (IABP)
      use in two Australasian centres and evaluate the effect of final IABP tip
      position on outcome. Indications for counterpulsation, patient demographics and
      in-hospital outcomes and complications were retrospectively collected. The chest
      X-ray reports provided the 'final' position of the IABP tip. The position was
      defined as acceptable (tip was seen just below the aortic arch, at T2-T5
      vertebrae), malpositioned (tip > 5 cm below aortic arch or at T5-T6) or severely
      malpositioned (tip > 10 cm below aortic arch or at T7 or below).?Major
      complications were considered a composite of death secondary to IABP, major limb
      ischaemia, major IABP malfunction, balloon rupture or haemorrhage, severe renal
      dysfunction (rise in creatinine > 200 umol/l), stroke and mesenteric ischaemia.
      Six hundred and forty-five cases were reviewed. The overall major complication
      rate was 26.2% and 24.3%. Severe renal impairment was the most common
      complication (16.6%), and second, severe catheter dysfunction (5.4%). ?Final IABP
      position was acceptable in 39.9%, malpositioned in 11.1%,?severely malpositioned
      in 6.7% and unavailable for 42.4%. Logistic regression analysis showed IABP tip
      malposition (compared with satisfactory position odds ratio=3.9 [95% confidence
      interval=2.0-7.6, P < 0.001] and severely malpositioned odds ratio=13.0 [95%
      confidence interval 5.3-31.7, P < 0.001]) was associated with major complications
      more than the presence of shock (odds ratio=3.8, confidence interval=2.1-6.8 P <
      0.001). The acceptance of a less-than-ideal final position was highly predictive
      of morbidity directly related to IABP device therapy. 

PMID- 25579292
TI  - Effect of different phenylephrine bolus doses for treatment of hypotension during
      spinal anaesthesia in patients undergoing elective caesarean section.
AB  - The efficacy of phenylephrine might be improved by giving doses higher than that
      traditionally used (100 ug). This study compared the effects of three initial
      bolus doses of intravenous phenylephrine; 100 ug (group P100), 125 ug (group
      P125) and 150 ug (group P150), for the treatment of post-spinal hypotension in
      patients undergoing elective caesarean delivery. If hypotension was not corrected
      by this dose, additional boluses of 25 ug were given every minute. Further
      hypotensive episodes were treated with half the initial bolus dose, followed by
      25 ug boluses, as required. Umbilical arterial and venous blood samples were
      obtained for blood gas analysis and Apgar scores recorded. One hundred and twenty
      subjects (40 per group) who developed post-spinal hypotension (75%) were included
      in this randomised, double blind trial. Although systolic blood pressure was
      higher at certain time-points after 150 ug phenylephrine, there were no
      statistically significant differences in the effectiveness of the first bolus of
      phenylephrine to treat hypotension (85%, 95% and 95% in groups P100, P125 and
      P150, respectively, P=0.215); the additional dose of phenylephrine after the
      first bolus (P=0.810); the number of additional boluses (P=0.318) or of
      hypotensive episodes (P=0.118). There were no significant differences in the
      number of patients developing reactive hypertension or bradycardia, in maternal
      side-effects or in neonatal outcomes. Although the study may have been
      underpowered, initial phenylephrine bolus doses of 100 ug, 125 ug and 150 ug did
      not significantly differ in efficacy to treat post-spinal hypotension in these
      patients. 

PMID- 25579293
TI  - The effect of mechanical ventilator settings during ventilator hyperinflation
      techniques: a bench-top analysis.
AB  - Ventilator hyperinflations are used by physiotherapists for the purpose of airway
      clearance in intensive care. There is limited data to guide the selection of
      mechanical ventilator modes and settings that may achieve desired flow patterns
      for ventilator hyperinflation. A mechanical ventilator was connected to two lung
      simulators and a respiratory mechanics monitor. Peak inspiratory (PIFR) and
      expiratory flow rates (PEFR) were measured during manipulation of ventilator
      modes (pressure support ventilation [PSV], volume-controlled synchronised
      intermittent mandatory ventilation [VC-SIMV] and pressure-controlled synchronised
      intermittent mandatory ventilation [PC-SIMV]) and ventilator settings (including
      set tidal volume, positive end-expiratory pressure, inspiratory flow rate,
      inspiratory pause, pressure support, inspiratory time and/or inflation pressure).
      Additionally, each trial was conducted with high (0.05 l/cmH2O) and low (0.01
      l/cmH2O) compliance settings on the lung simulators. Each trial was dichotomised
      into success or failure under three categories (attainment of PIFR-PEFR less than
      or equal to 0.9, PEFR/PIFR greater than 17 l/min, PEFR greater than or equal to
      40 l/min). A total of 232 trials were conducted (96 VC-SIMV, 96 PC-SIMV, 40 PSV).
      A greater proportion of VC-SIMV trials were ceased due to high peak inspiratory
      pressures (35%). However, VC-SIMV trials were more likely to be successful at
      meeting all three outcome measures (26 VC-SIMV trials, 7 PC-SIMV trials, 0 PSV
      trials). It was found that manipulation of settings in VC-SIMV mode appears more
      successful than PSV and PC-SIMV for ventilator hyperinflations. 

PMID- 25579294
TI  - The time taken for the regional distribution of ventilation to stabilise: an
      investigation using electrical impedance tomography.
AB  - Electrical impedance tomography is a novel technology capable of quantifying
      ventilation distribution in the lung in real time during various therapeutic
      manoeuvres. The technique requires changes to the patient's position to place the
      electrical impedance tomography electrodes circumferentially around the thorax.
      The impact of these position changes on the time taken to stabilise the regional
      distribution of ventilation determined by electrical impedance tomography is
      unknown. This study aimed to determine the time taken for the regional
      distribution of ventilation determined by electrical impedance tomography to
      stabilise after changing position. Eight healthy, male volunteers were connected
      to electrical impedance tomography and a pneumotachometer. After 30 minutes
      stabilisation supine, participants were moved into 60 degrees Fowler's position
      and then returned to supine. Thirty minutes was spent in each position.
      Concurrent readings of ventilation distribution and tidal volumes were taken
      every five minutes. A mixed regression model with a random intercept was used to
      compare the positions and changes over time. The anterior-posterior distribution
      stabilised after ten minutes in Fowler's position and ten minutes after returning
      to supine. Left-right stabilisation was achieved after 15 minutes in Fowler's
      position and supine. A minimum of 15 minutes of stabilisation should be allowed
      for spontaneously breathing individuals when assessing ventilation distribution.
      This time allows stabilisation to occur in the anterior-posterior direction as
      well as the left-right direction. 

PMID- 25579295
TI  - Minimum effective anaesthetic volume of 0.5% ropivacaine for ultrasound-guided
      popliteal sciatic nerve block in patients undergoing foot and ankle surgery:
      determination of ED50 and ED95.
AB  - Compared to nerve stimulation or classic paraesthesia techniques, ultrasound (US)
      guided popliteal sciatic nerve block requires a smaller volume of local
      anaesthetic. The up-and-down method was used to determine the minimum effective
      anaesthetic volume of 0.5% ropivacaine necessary for US-guided popliteal sciatic
      nerve block to achieve successful surgical anaesthesia for foot and ankle
      surgery. The study included 32 patients receiving an US-guided popliteal sciatic
      nerve bock. The starting dose of 0.5% ropivacaine was set at 30 ml, which was
      decreased by 3 ml if the block succeeded and increased by 3 ml if the block
      failed. After the injection of local anaesthetic, the degree of sensory and motor
      blockade of the tibial and common peroneal nerves was assessed every 5 minutes
      for 30 minutes. The ED50 and ED95 volumes of local anaesthetic were 6 ml and 16
      ml, respectively. The success rates of sensory blockade of the tibial nerve and
      common peroneal nerve were 69% and 88%, respectively. The success rates of motor
      blockade of these nerves were 75% and 90%, respectively. The ED50 and ED95 of
      0.5% ropivacaine for US-guided popliteal sciatic nerve block were 6 ml and 16 ml,
      respectively. 

PMID- 25579296
TI  - Safe duration of postoperative monitoring for malignant hyperthermia patients
      administered non-triggering anaesthesia: an update.
AB  - The postoperative care of malignant hyperthermia (MH) patients is subject to
      international variation, with a paucity of data in the literature to guide
      management. Over a series of three studies, our aim was to evaluate whether MH
      susceptible patients (and relatives who had not yet been investigated), who had
      received a non-triggering anaesthetic, could be managed in the same way as the
      standard surgical population. Following a retrospective study, 206 anaesthetics
      were administered in a prospective second study to MH-susceptible/related
      individuals who were monitored for a minimum of one hour in the post anaesthesia
      care unit and a further 90 minutes in a step-down facility. No problems relating
      to MH were encountered. The postoperative monitoring time was subsequently
      changed and, in a third study, patients were managed no differently from standard
      surgical patients. One hundred and twenty-five anaesthetics were administered
      with no evidence of problems. This data shows that standard postoperative
      monitoring times are safe and appropriate in MH-susceptible patients. 

PMID- 25579297
TI  - Near-infrared spectroscopy-based microcirculatory assessment in acute atrial
      fibrillation.
AB  - Near-infrared spectroscopy is a means of assessing microcirculatory function, but
      has not been studied in atrial fibrillation (AF). We evaluated the effect of
      acute AF on thenar eminence near-infrared spectroscopy-derived microcirculatory
      variables. Stable patients presenting to the emergency department with acute
      onset AF underwent dynamic near-infrared spectroscopy assessment with a three
      minute vascular occlusion test (VOT). This was repeated after cardioversion to
      sinus rhythm (SR). Each assessment included baseline tissue oxygen saturation
      (StO2), slope of StO2 decrease during VOT, slope of StO2 increase post VOT,
      minimum and maximum StO2, amplitude of StO2 response and post-ischaemic
      hyperperfusion. Pre and post cardioversion values were compared by Wilcoxon
      signed-rank test. Twelve participants (seven male, five female) with a median age
      of 63 years (interquartile range 52 to 70 years) were enrolled. Median baseline
      StO2 was 74% before and 77% after cardioversion (P=0.03). The median slope of
      StO2 decrease during VOT was -0.19%/second and -0.16%/second (P=0.018) and the
      median slope of StO2 increase post VOT was 3.03%/second and 2.56%/second
      (P=0.002), pre and post cardioversion, respectively. Minimum StO2 was lower (39%
      versus 52%, P=0.002) and the amplitude of StO2 response greater (49% versus 40%,
      P=0.005) in AF, but there was no significant difference in maximum StO2 or the
      degree of reperfusion hyperaemia. In summary, baseline and minimum StO2 were
      lower with a greater ischaemic decrease in StO2 during AF, reflecting reduced
      tissue perfusion, compared with sinus rhythm. Recovery after ischaemia was higher
      in AF, suggesting normalisation of capillary recruitment during ischaemia. 

PMID- 25579298
TI  - A retrospective survey of substance abuse in anaesthetists in Australia and New
      Zealand from 2004 to 2013.
AB  - A questionnaire on substance abuse was distributed electronically to the heads of
      185 Australian and New Zealand College of Anaesthetists accredited anaesthesia
      departments in Australia and New Zealand. The response rate was 57%. From January
      2004 to December 2013, 61 cases of substance abuse were identified, giving an
      estimated incidence of 1.2 cases per 1000 anaesthetist years. Of 44 detailed
      reports completed, the majority were aged between 30 and 49 years, were male and
      of specialist grade. However, when corrected for gender and grade, the estimated
      overall incidence was higher in females and twice as high for trainees compared
      with specialists. When compared with prior surveys, the pattern of substance
      abuse in Australia and New Zealand appears to have changed significantly, with a
      notable increase in propofol and alcohol abuse and a decrease in reported cases
      of opioid abuse. Common presenting features of abuse included intoxication and
      witnessed abuse. Seventy percent of cases had more than one comorbid condition,
      most frequently either mental health or family problems. Only 32% of abusers had
      made a long-term recovery within the specialty. Death was the eventual outcome in
      18% overall, with a particularly high mortality associated with propofol abuse
      (45%). Trainee suicide from all causes was reported at three times the rate of
      specialists. The findings indicate that substance abuse remains a significant
      problem in Australia and New Zealand and is associated with a significant
      mortality rate. 

PMID- 25579299
TI  - Is a high serum vitamin B12 level associated with an increased mortality in
      critically ill surgical patients?

PMID- 25579300
TI  - Ultrasound-guided axillary tunnel block: the 'comet tail' block.

PMID- 25579302
TI  - Attitudes toward reciprocity, preferred status and other organ donation policies:
      a survey of the Australian and New Zealand intensive care community.

PMID- 25579301
TI  - Cauda equina syndrome as a result of inadvertent intrathecal injection of sodium
      thiopentone.

PMID- 25579303
TI  - Use of transthoracic echocardiography to confirm pulmonary artery catheter
      placement.

PMID- 25579304
TI  - Airway management of low tracheal rupture.

PMID- 25579305
TI  - An inexpensive, sterile and disposable praecordial stethoscope.

PMID- 25579306
TI  - Quality, evidence and statistics-a comment on article by Conti et al.

PMID- 25579307
TI  - Drug labelling is a small piece of the medication error puzzle.

PMID- 25579308
TI  - Experience using a new staged extubation kit in patients with a known difficult
      airway.

PMID- 25579309
TI  - [Giant cell tumor of the lumbar spine. Case report and review of the literature].
AB  - We report the case of a 32-year-old patient complaining of chronic low back pain
      radiating to his left thigh. His MRI showed a lytic L1 vertebral body injury. A
      transpedicular biopsy confirmed the diagnosis of giant cell tumor. He underwent a
      L1 vertebrectomy and vertebral body replacement with a titanium cylinder using
      anterior approach, followed by the removal of the L1 posterior arch and the
      placement of pedicle screws through a posterior approach. The giant cell tumor is
      a rare benign primary bone tumor that can be locally aggressive and can
      potentially spread to other areas, usually to the lungs. Although it most
      frequently affects long bones, approximately 10% of tumors are located in the
      spine. To minimise the risk of recurrence, the elective management option is
      surgery. 

PMID- 25579319
TI  - Development of a Comprehensive Programme to Prevent and Reduce the Negative
      Impact of Railway Fatalities, Injuries and Close Calls on Railway Employees.
AB  - AIM: This article presents a strategy to prevent trauma, support and care for
      railway personnel who experience critical incidents (CI) on the job, usually
      fatalities by accident or suicide. METHOD: We reviewed all publications on CI
      management, support and care practices in the railway industry, as well as
      practices in place in Canada (unpublished protocols). Semi structured interviews
      were conducted with 40 train engineers and conductors involved in CIs and the
      content was coded and analysed quantitatively. RESULTS: Employees' satisfaction
      with the help received after the incident varies according to the behaviour of
      the local manager, company officers and police, the level of compliance with
      existing company protocols to help them, the presence of unmet expectations for
      support and care, their perceived competency of clinicians they consulted and the
      level of trust toward their employers. CONCLUSION: On the basis of the interview
      results, the review of existing railway practices and discussions with railway
      stakeholders, a model protocol was developed for a comprehensive workplace
      prevention, support and care protocol to reduce the negative impact of railway
      critical incidents on employees. This protocol includes preventive actions before
      traumatic events occur, immediate responses at the site of incident,
      interventions within the first few days after the incident and longer term
      support and interventions provided by the company and by outsourced experts.

PMID- 25579320
TI  - Therapeutic uses of melatonin and melatonin derivatives: a patent review (2012 -
      2014).
AB  - INTRODUCTION: Melatonin is a neurohormone involved in the regulation of circadian
      rhythms, with potent antioxidant activity. It has a wide functional repertoire,
      with effects almost on all tissues and organs. It is mainly used as a dietary
      supplement for sleep regulation and re-synchronization of disrupted circadian
      rhythms. Melatonin has very low toxicity, but some pharmacokinetic issues, such
      as limited oral bioavailability and short half-life, limit its tissue
      availability. AREAS COVERED: Patents and patent applications from 2012 to
      September 2014 in which melatonin or synthetic analogues are claimed for the
      prevention or treatment of pathological conditions. EXPERT OPINION: Melatonin is
      considered a valuable substance that can be safely administered for the
      prevention and treatment of many diverse diseases. A major trend in 2012 - 2014
      patents is the co-administration of melatonin with other drugs to increase the
      efficacy of the treatment and reduce side-effects. Two different actions have
      been combined in hybrid ligands (e.g., melatonin-tamoxifen and melatonin-tacrine
      derivatives). Further experimental evidence is needed to support the usefulness
      of these approaches. The number of new melatonin analogues has shown a marked
      decrease in the past 3 years, with claimed applications mainly as hypnotic or
      antioxidant agents.

PMID- 25579321
TI  - Encephalopathy following melphalan administration.
AB  - OBJECTIVE: To describe a rare case of encephalopathy following melphalan
      administration. Presentation and intervention:: A 59-year-old female with
      multiple myeloma developed encephalopathy following administration of melphalan.
      After ruling out other aetiologies, we hypothesized elevated cytokines from
      systemic inflammatory response to melphalan as the likely aetiology. The TNF
      alpha level was found to be significantly elevated. Plasmapharesis was performed
      which reduced the level of cytokines, and also improved the patient's
      neurological status. CONCLUSION: Melphalan administration, especially in renally
      impaired patients, may lead to development of encephalopathy. Based on our case
      report, we suggest that elevated levels of cytokines could be the underlying
      mechanism of worsening mental status.

PMID- 25579322
TI  - Acute ischaemic stroke and myocardial infarction after chemotherapy with
      vinorelbine for non-small cell lung cancer: a case report.
AB  - Vinorelbine is an important chemotherapeutic agent which is used in metastatic
      non-small cell lung cancer. Case reports have described the occurrence of acute
      cardiac ischaemic events as a side effect. It has not been established whether
      the suspected mechanisms for cardiac ischaemia might also cause other vascular
      events. We report about a 70-year-old male with metastatic non-small cell lung
      cancer who received vinorelbine as an outpatient. The patient presents with a
      cardiovascular risk profile. He was admitted to the hospital 3 days later with
      acute left-sided hemiplegia and hemianopia. Brain computed tomography (CT)
      demonstrated acute right hemispheric ischaemic stroke. Nine days after admission,
      the patient additionally suffered ST elevation myocardial infarction. A coronary
      angiogram demonstrated high grade stenosis of the right coronary artery treated
      with two bare-metal stents. Caution should be noted in patients who present with
      a cardiovascular risk profile as they might be vulnerable experiencing acute
      ischaemic events.

PMID- 25579323
TI  - Asymmetrical disassortative pollination in a distylous primrose: the
      complementary roles of bumblebee nectar robbers and syrphid flies.
AB  - Heterostyly is a floral polymorphism characterized by reciprocal herkogamy
      maintained through high levels of mating between morphs, serviced by appropriate
      pollinators. We studied how differential efficiency and abundance of distinct
      pollinators affect plant female reproduction in self- and intra-morph
      incompatible distylous Primula secundiflora. Bumblebees and syrphid flies were
      found to be the most abundant floral visitors. Bumblebees frequently exhibited
      nectar-robbing behavior. Because the robbing holes were always situated between
      the high- and low-level organs on both morphs, nectar-robbing bumblebees only
      pollinated S-styled flowers. L-styled flowers set four times as many seeds as did
      S-styled flowers after being visited by pollen-collecting syrphid flies. The
      natural female fecundity and the magnitude of pollen limitation varied between
      the morphs within populations because of the mosaic distribution of nectar
      robbing bumblebees and syrphid flies. L-styled flowers and S-styled flowers set
      the same number of seeds after supplemental hand pollination, indicating
      equivalent female reproductive potential. We suggest that bumblebee nectar
      robbers and syrphid flies play an important role in sustaining the floral
      dimorphism of heterostyly in P. secundiflora because of their complementary roles
      in the pollination system. 

PMID- 25579324
TI  - The lag from FDA approval to published cost-utility evidence.
AB  - The lag between FDA approval and publication of cost-utility evidence can hamper
      payers from accounting for value for money in coverage and reimbursement
      decisions. We examine this gap, and whether it has changed over time. For drugs
      approved from 2000 to 2010 (n = 274), we searched the Tufts Medical Center Cost
      Effectiveness Analysis Registry to identify relevant cost-utility analyses
      (CUAs). We identified 127 (46%) drugs associated with a CUA, 62 of which had a
      CUA published in the 3 years following its approval. Compared with drugs approved
      from 2000 to 2003, a greater proportion of those approved from 2004 to 2006, and
      from 2007 to 2010, was associated with a CUA published in the 3 years following
      approval (13 vs 25% [p = 0.06] and 13 vs 32% [p < 0.01], respectively). Study
      findings indicate that payers now have slightly more rapid access to published
      CUAs. 

PMID- 25579326
TI  - Thermoelectric properties and chlorine doping effect of In4Pb0.01Sn0.03Se2.9Clx
      polycrystalline compounds.
AB  - We investigated the thermoelectric properties of Cl-doped polycrystalline
      compounds In4Pb0.01Sn0.03Se2.9Clx (x = 0.02, 0.04, and 0.06). X-ray diffraction
      measurement shows a gradual change in lattice volume for x <= 0.04 without any
      impurity phases indicating a systemic change in Cl doping. The Cl doping in the
      compounds has the effect of increasing carrier concentration and the effective
      mass of carriers, resulting in an increase in power factor at a high temperature
      (~700 K). Because of the increased electrical conductivity at a high temperature,
      the dimensionless thermoelectric figure of merit ZT reaches 1.25 at 723 K for the
      x = 0.04 Cl-doped compound, which is a relatively high value for n-type
      polycrystalline materials. 

PMID- 25579325
TI  - Antinociceptive effect of intracerebroventricular administration of glycine
      transporter-2 inhibitor ALX1393 in rat models of inflammatory and neuropathic
      pain.
AB  - Glycinergic transmission has an important role in regulating nociception in the
      spinal cord. The glycine transporter-2 (GlyT2) is localized at presynaptic
      terminals of glycinergic neurons and eliminates glycine from the synaptic cleft
      to terminate glycinergic transmission. Systemic and intrathecal administration of
      GlyT2 inhibitors alleviate various types of pain. Although the GlyT2s and glycine
      receptors are widely distributed in the central nervous system, little is known
      about the role of glycinergic transmission in pain perception at supraspinal
      regions. The present study examined the antinociceptive effect of
      intracerebroventricular (i.c.v.) administration of the selective GlyT2 inhibitor
      ALX1393 on inflammatory and neuropathic pain in experimental models. For i.c.v.
      administration, a guide cannula was implanted into the right lateral ventricle of
      male Sprague-Dawley rats. Normal rats were used to assess inflammatory
      nociception using the formalin test and motor function using the rotarod test.
      Chronic constriction injury (CCI) to the sciatic nerve was induced in the rats.
      The CCI rats were then used to assess mechanical, cold, and thermal hyperalgesia
      using the electronic von Frey test, cold plate test, and the plantar test,
      respectively. ALX1393 (25, 50, and 100 MUg) was administered i.c.v. to examine
      its effects on supraspinal antinociception. Supraspinal ALX1393 in normal rats
      suppressed the late-phase response in the formalin test but did not affect motor
      performance. In the CCI rats, ALX1393 inhibited mechanical and cold hyperalgesia
      in a dose-dependent manner. The antihyperalgesic effects of ALX1393 (100 MUg)
      were reversed completely by i.c.v. pretreatment with a glycine receptor
      antagonist strychnine (10 MUg). These results suggest that GlyT2 contributes to
      nociceptive transmission at supraspinal level and that the selective GlyT2
      inhibitor is a promising candidate for the treatment of inflammatory and
      neuropathic pain without causing motor dysfunction.

PMID- 25579343
TI  - Therapeutics and carriers: the dual role of proteins in nanoparticles for ocular
      delivery.
AB  - Blindness and visual impairment affect millions of people worldwide and have a
      very important impact on patients quality of life. Proteins and peptides
      represent nowadays an important therapeutic tool for the treatment of ocular
      diseases but, despite their potential, have significant limitations, as the
      administration of protein-based pharmaceuticals represents a real challenge.
      Moreover, administration of ocular medications is difficult due to the peculiar
      structure of this organ and the presence of numerous barriers protecting the eye
      inner structure. Nanoencapsulation of peptides and proteins presents a number of
      advantages for their ocular delivery since it can protect the drug from metabolic
      activity, control and sustain the release and increase drug bioavailability after
      topical or intravitreal administration. In fact, nanoparticulate formulations are
      contributing to overcome ocular barriers, such as the corneal or the blood
      retinal barrier, improve the residence time in the eye, increase local drug
      level, reduce the drug dosage and showing improved performance when compared to
      conventional formulations. Besides, proteins have also been proposed for the
      preparation of nanocarriers intended for ophthalmic administration, since they
      are highly biocompatible, biodegradable and easily modified to link surface
      ligands. The present review focuses the attention on the use of proteins in
      ocular drug delivery nanotechnology: their dual role as both therapeutics and
      carriers has been critically evaluated and discussed. 

PMID- 25579345
TI  - Opportunities and challenges for the nasal administration of nanoemulsions.
AB  - Nasal delivery has become a growing area of interest for drug administration as a
      consequence of several practical advantages, such as ease of administration and
      non-invasiveness. Moreover, the avoidance of hepatic first-pass metabolism and
      rapid and efficient absorption across the permeable nasal mucosa offer a
      promising alternative to other traditional administration routes, such as oral or
      parenteral delivery. In fact, nasal delivery has been proposed for a number of
      applications, including local, systemic, direct nose-to-brain and mucosal vaccine
      delivery. Nanoemulsions, due to their stability, small droplet size and optimal
      solubilization properties, represent a versatile formulation approach suitable
      for several administration routes. Nanoemulsions demonstrated great potential in
      nasal drug delivery, increasing the absorption and the bioavailability of many
      drugs for systemic and nose-to-brain delivery. Furthermore, they act as an active
      component, i.e. an adjuvant, in nasal mucosal vaccinations, displaying the
      ability to induce robust mucosal immunity, high serum antibodies titres and a
      cellular immune response avoiding inflammatory response. Interestingly,
      nanoemulsions have not been proposed for the treatment of local ailments of the
      nose. Despite the promising results in vitro and in vitro, the application of
      nanoemulsions for nasal delivery in humans appears mainly hindered by the lack of
      detailed toxicology studies to determine the effect of these formulations on the
      nasal mucosa and cilia and the lack of extensive clinical trials.

PMID- 25579344
TI  - Recent advances in nanoparticle carriers for coordination complexes.
AB  - Coordination compounds are substances in which a central metal atom is bonded to
      nonmetal atoms, or groups of atoms, called ligands. Examples include vitamin B12,
      hemoglobin, chlorophyll, dyes and pigments, as well as catalysts used in organic
      synthesis. Coordination compounds have received much attention in recent years.
      This interest was prompted by the discovery that several coordination compounds
      exhibit activity against bacteria, fungi and cancer. Some coordination compounds
      are not in clinical use, because of poor water solubility. Because they are
      unable to cross the lipid membranes of cells, bioavailability and efficacy are
      low. Some researchers have applied nanotechnology to coordination compounds,
      hoping to reduce the number of doses required and the severity of side effects,
      and also to improve biological activity. Nanotechnology can deliver active
      components in sufficient concentrations throughout treatment, guiding it to the
      desired location of action; conventional treatments do not meet these
      requirements. In this study we review some drug delivery systems based on
      nanotechnology, such as microemulsions (MEs), cyclodextrin (CD), polymeric
      nanoparticles (PN), solid lipid nanoparticles (SLNs), nanostructured lipid
      carriers (NLCs), magnetic and gold nanoparticles (MNPs / AuNPs) and liquid
      crystalline systems (LC), and coordination compounds. 

PMID- 25579346
TI  - Graphene oxide: a carrier for pharmaceuticals and a scaffold for cell
      interactions.
AB  - During the last ten years, graphene oxide has been explored in many applications
      due to its remarkable electroconductivity, thermal properties and mobility of
      charge carriers, among other properties. As discussed in this review, the
      literature suggests that a total characterization of graphene oxide must be
      conducted because oxidation debris (synthesis impurities) present in the graphene
      oxides could act as a graphene oxide surfactant, stabilizing aqueous dispersions.
      It is also important to note that the structure models of graphene oxide need to
      be revisited because of significant implications for its chemical composition and
      its direct covalent functionalization. Another aspect that is discussed is the
      need to consider graphene oxide surface chemistry. The hemolysis assay is
      recommended as a reliable test for the preliminary assessment of graphene oxide
      toxicity, biocompatibility and cell membrane interaction. More recently, graphene
      oxide has been extensively explored for drug delivery applications. An important
      increase in research efforts in this emerging field is clearly represented by the
      hundreds of related publications per year, including some reviews. Many studies
      have been performed to explore the graphene oxide properties that enable it to
      deliver more than one activity simultaneously and to combine multidrug systems
      with photothermal therapy, indicating that graphene oxide is an attractive tool
      to overcome hurdles in cancer therapies. Some strategic aspects of the
      application of these materials in cancer treatment are also discussed. In vitro
      studies have indicated that graphene oxide can also promote stem cell adhesion,
      growth and differentiation, and this review discusses the recent and pertinent
      findings regarding graphene oxide as a valuable nanomaterial for stem cell
      research in medicine. The protein corona is a key concept in nanomedicine and
      nanotoxicology because it provides a biomolecular identity for nanomaterials in a
      biological environment. Understanding protein corona-nanomaterial interactions
      and their influence on cellular responses is a challenging task at the
      nanobiointerface. New aspects and developments in this area are discussed. 

PMID- 25579347
TI  - Highlights in peptide nanoparticle carriers intended to oral diseases.
AB  - New biocompatible nanomaterials are leading to a range of emerging health
      treatments. Thus, peptide drugs present in oral diseases, such as caries,
      periodontal diseases and oral cancer, are highlighting into clinical practice
      because the peptides can have an influence the growth of tumor cells or
      microorganisms and its can exhibit direct cytotoxic activity towards cancer cells
      or microbial cells. Therefore, it is interesting to speculate what are the
      natural or synthetic peptides that can be used to develop novel strategies to
      fight cancer diseases or microbial cells, and so, to represent a novel family of
      anticancer or antimicrobial agents. The use of buccal drug delivery systems,
      especially nanoparticles, to carrier peptides shows to be very interesting,
      because these systems can protect the peptide against enzymatic degradation, in
      addition to target inaccessible sites. However, this peptide delivery system
      seems to be unexplored by researchers. On the hand, the application of drug
      delivery systems for oral diseases could be a proposed treatment for these
      diseases, including the treatment or co-treatment with other therapies, such as
      photodynamic therapy, of antimicrobial, periodontal diseases and cancer, or even
      in the early diagnosis of cancer. The objective of this study is to present a
      systematic review of nanotechnology-based peptides delivery systems intended to
      oral diseases. 

PMID- 25579348
TI  - Nanoparticles in the treatment of mental disorders: a new tool in the psychiatric
      medication.
AB  - The use of the nanotechnology in the development of new drugs has had in the last
      years a very widespread presence in the pharmaceutical industry. Diverse diseases
      that are treated by means of conventional administration systems as capsules,
      covered tablets or injectable not always have the therapeutic effect expected due
      to its bioavailability, solubility in aqueous medium and the stability of the
      excipients that they accompany to the drug. It is for this reason that the
      formation of nanoparticles either from organic sources as natural polymers like
      chitosan or synthetic like poly-epsilon-caprolactone (PCL) affording the
      inclusion of diverse liposoluble active compounds, they have given excellent
      results in the incipient treatment of behavior disorders that are necessary drugs
      that should remain close of active sites at the time. Thus, this review shows the
      formation of nanoparticles for a direct application of the psychiatric
      medication, may be considered as a new pharmacological tool by its low
      cytotoxicity and high efficiency. 

PMID- 25579349
TI  - Opportunities offered by chitosan-based nanotechnology in mucosal/skin drug
      delivery.
AB  - Chitosan (CS) based nanocarriers have been extensively studied starting from
      early 90s. The unique properties of CS and in particular its capability to
      interact with various epithelia and its mucoadhesion potential have attracted
      many researchers. The mild preparation conditions of CS nanosystems offer the
      opportunities to load stress sensitive hydrophilic macromolecules such as
      proteins and genetic materials. Moreover CS nanosystems are able to protect their
      cargo from the environment (pH, enzymes). The safety issues related to this
      polymer seem in part overcome at least for CS as polymeric solution. For this
      reason skin and mucosae, in particular buccal and vaginal ones, seem the more
      promising administration routes with lower technical and regulatory challenges.
      Even if several papers focused on CS nanocarriers for skin and mucosal (buccal
      and vaginal) administration have been published, other work should be done aiming
      at optimizing CS nanocarriers in view of clinical applications. 

PMID- 25579350
TI  - Pulmonary drug delivery: a role for polymeric nanoparticles?
AB  - Pulmonary drug delivery represents the best way of treating lung diseases, since
      it allows direct delivery of the drug to the site of action, with few systemic
      effects. Meanwhile, the lungs may be used as a portal of entry to the body,
      allowing systemic delivery of drugs via the airway surfaces into the bloodstream.
      In both cases, the therapeutic effect of the inhaled drug can be optimized by
      embedding it in appropriately engineered inhalable carriers, which can protect
      the drug against lung defense mechanisms and promote drug transport across the
      extracellular and cellular barriers. To this purpose, the attention has been very
      recently focused on polymeric nanoparticles (NPs). The aim of this review is to
      offer an overview on the recent advances in NPs for pulmonary drug delivery.
      After a description of the main challenges encountered in developing novel
      inhaled products, the design rules to engineer polymeric NPs for inhalation, and
      in so doing to overcome barriers imposed by the lungs anatomy and physiology, are
      described. Then, the state-of-art on inhalable biocompatible polymeric NPs based
      on enzymatically-degradable natural polymers and biodegradable poly(ester)s is
      presented, with a special focus on NP-based dry powders for inhalation. Finally,
      the in vitro/in vivo models useful to address the never-ending toxicological
      debate related to the use of NPs for inhalation are described.

PMID- 25579351
TI  - Nitric oxide releasing nanomaterials for cancer treatment: current status and
      perspectives.
AB  - Nitric oxide (NO) is known to have dichotomous effects on cancer biology, acting
      as a pro- or antineoplastic agent. Low concentrations of NO are reported to
      promote tumor growth, whereas high NO influx acts as a potent tumor repressor,
      leading to cytotoxicity and apoptosis. There is increasing interest in developing
      NO-releasing materials as potent tumoricidal agents in which high and localized
      concentrations of NO may be directly released in a sustained manner to the tumor
      site. Nanomaterials allied to NO donors have emerged as a promising strategy in
      cancer treatment. In this context, this review summarizes the roles of NO in
      cancer biology and highlights the therapeutic potential effects of NO-releasing
      nanomaterials based on polymeric nanoparticles, dendritic polymers, liposomes,
      silica nanoparticles, metallic nanoparticles and quantum dots in combating tumor
      cells. 

PMID- 25579352
TI  - Pragmatic research in ophthalmology: need of the hour.

PMID- 25579353
TI  - Long-term follow-up of zonulo-hyaloido-vitrectomy for pseudophakic malignant
      glaucoma.
AB  - PURPOSE: To report long-term follow-up of zonulo-hyaloido-vitrectomy (ZHV) via
      anterior approach for pseudophakic malignant glaucoma refractory to medical
      treatment. DESIGN: Noncomparative case-series. MATERIALS AND METHODS: Medical
      records of 9 patients who sought treatment for aqueous humor misdirection
      refractory to medical treatment were reviewed. All patients underwent anterior
      vitrectomy, hyaloido-zonulectomy, and peripheral iridectomy (PI) via an anterior
      approach. Main outcome measures were preoperative and postoperative visual
      acuity, intraocular pressure, medications, slit-lamp examination, and fundus
      findings. RESULTS: 10 eyes of 9 patients (7 female, 2 male) who underwent ZHV for
      refractory pseudophakic malignant glaucoma between 2003 and 2010 were included in
      this case-series. The mean age of patients was 77.4 +/- 9.0 years, mean follow-up
      duration 50.2 +/- 27.2 months. Recurrence of malignant glaucoma was noted in 40%
      (four cases) after a successful ZHV on long-term follow-up. CONCLUSIONS: An
      anterior segment surgeon can treat malignant glaucoma refractory to medical
      treatment successfully by vitrectomy, hyaloido-zonulectomy, and PI. This can be
      done via an anterior approach and patients require long follow-up to rule out a
      relapse despite a successful outcome in the short term.

PMID- 25579354
TI  - Automated diabetic retinopathy imaging in Indian eyes: a pilot study.
AB  - AIM: To evaluate the efficacy of an automated retinal image grading system in
      diabetic retinopathy (DR) screening. MATERIALS AND METHODS: Color fundus images
      of patients of a DR screening project were analyzed for the purpose of the study.
      For each eye two set of images were acquired, one centerd on the disk and the
      other centerd on the macula. All images were processed by automated DR screening
      software (Retmarker). The results were compared to ophthalmologist grading of the
      same set of photographs. RESULTS: 5780 images of 1445 patients were analyzed.
      Patients were screened into two categories DR or no DR. Image quality was high,
      medium and low in 71 (4.91%), 1117 (77.30%) and 257 (17.78%) patients
      respectively. Specificity and sensitivity for detecting DR in the high, medium
      and low group were (0.59, 0.91); (0.11, 0.95) and (0.93, 0.14). CONCLUSION:
      Automated retinal image screening system for DR had a high sensitivity in high
      and medium quality images. Automated DR grading software's hold promise in future
      screening programs.

PMID- 25579355
TI  - Effectiveness of low vision services in improving patient quality of life at
      Aravind Eye Hospital.
AB  - CONTEXT: In India, where the heavy burden of visual impairment exists, low vision
      services are scarce and under-utilized. AIMS: Our study was designed to survey
      the effectiveness of low vision exams and visual aids in improving patient
      quality of life in southern rural India. SUBJECTS AND METHODS: The low vision
      quality of life (LVQOL) questionnaire measures vision-related quality of life
      through 25 questions on a Likert scale of 0-5 that pertain to (1) mobility,
      distance vision, and lighting; (2) psychological adjustment; (3) reading and fine
      work; and (4) activities of daily living. This tool was translated into Tamil and
      verbally administered to 55 new low vision referral patients before their first
      visit at the low vision clinic at Aravind Eye Hospital. Low vision aids (LVAs)
      were prescribed at the discretion of the low vision specialist. 1-month later,
      the same questionnaire was administered over the phone. RESULTS: About 44 of 55
      low vision patients completed baseline and follow-up LVQOL surveys, and 30 normal
      vision controls matched for age, gender, and education were also surveyed
      (average 117.34 points). After the low vision clinic visit, the low vision group
      demonstrated a 4.55-point improvement in quality of life (from 77.77 to 82.33
      points, P = 0.001). Adjusting for age, gender, and education, the low vision
      patients who also received LVAs (n = 24) experienced an even larger increase than
      those who did not (n = 20) (8.89 points, P < 0.001). CONCLUSION: Low vision
      services and visual aids can improve the quality of life in South Indian rural
      population regardless of age, gender, and education level. Thus, all low vision
      patients who meet the criteria should be referred for evaluation.

PMID- 25579356
TI  - Long-term results after primary intraocular lens implantation in children
      operated less than 2 years of age for congenital cataract.
AB  - PURPOSE: To study the long-term outcome of cataract surgery with primary
      intraocular lens (IOL) in children <2 years. MATERIALS AND METHODS: Retrospective
      analysis of bilateral cases that were operated before 2 years age for congenital
      cataract. All underwent primary posterior capsulotomy with anterior vitrectomy
      and primary IOL implantation. Only those with a follow-up of at least 8 years
      were evaluated. RESULTS: Twenty-six eyes of 13 children with bilateral cataract
      met the inclusion criteria. Average age at surgery was 14.15 months with a mean
      follow-up of 102 months. Average preoperative axial length (AL) was 19.93 mm.
      There was a refractive shift from a mean spherical equivalent of 1.64 D at 2
      weeks after surgery to -1.42 D measured at last follow-up. Twenty-four eyes out
      of 26 (92%) achieved final visual acuity (VA) of 6/18 or more at last follow-up
      with 19/26 (73%) having acuity of 6/12 or greater. Raised intraocular pressure
      was documented in one eye only. Average AL recorded at last follow-up was 22.21
      mm. CONCLUSION: Primary IOL implantation in children <2 years is a safe surgical
      procedure with excellent long-term results. The myopic shift is well-controlled
      and final VA achieved is reasonably good.

PMID- 25579357
TI  - A pharmacoeconomic analysis to determine the relative cost-effectiveness of
      bimatoprost 0.03% eye drops and brimonidine 0.2% eye drops in patients of primary
      open-angle glaucoma/ocular hypertension.
AB  - AIMS: The aim was to compare efficacy and cost-effectiveness of bimatoprost 0.03%
      and brimonidine 0.2% in primary open-angle glaucoma (POAG)/ocular hypertension
      (OHT). SETTINGS AND DESIGN: Open, randomized, cross-over, comparative study.
      MATERIALS AND METHODS: Forty patients of POAG or OHT with intraocular pressure
      (IOP) <30 mm Hg were included in the study after a written informed consent. The
      patients were divided randomly into two groups of 20 patients each. Patients of
      group A were administered bimatoprost 0.03% eye drops once daily, and those of
      group B brimonidine 0.2% eye drops twice daily for a period of 4 weeks. After a
      washout period of 4 weeks, the patients were crossed over that is, group A was
      administered brimonidine 0.2% and group B bimatoprost 0.03%. Fall in IOP at 4
      weeks was recorded. The daily cost of each drug was calculated by maximum retail
      price and the average number of drops per bottle. The cost-effectiveness was then
      calculated as the cost of drug/mm Hg fall in IOP. STATISTICS: Independent samples
      t-test was used to compare the efficacy of both drugs. RESULTS: IOP lowering with
      bimatoprost (8.9 +/- 1.598 mm Hg) was significantly (P < 0.0001) higher than
      brimonidine (6.55 +/- 1.26 mm Hg). The number of drops/ml were 33.43 +/- 0.52 and
      25.49 +/- 0.26, respectively, for bimatoprost and brimonidine. Treatment with
      bimatoprost was costlier than brimonidine with daily costs/eye Rs. 4.02 +/- 0.06
      and 3.14 +/- 0.03, yearly costs/eye Rs. 1467.46 +/- 20.74 and 1147.75 +/- 11.15,
      respectively. Bimatoprost was more cost-effective than brimonidine with the cost
      effectiveness ratio (CER) respectively Rs. 13.10 +/- 2.61/mm Hg and Rs. 13.96 +/-
      2.86/mm Hg. Incremental CER Rs. 10.43/mm Hg implies lower costs/mm Hg extra IOP
      lowering by bimatoprost than Rs. 13.96 for brimonidine. CONCLUSION: In spite of
      being costlier, bimatoprost is more efficacious and cost-effective than
      brimonidine.

PMID- 25579358
TI  - Evaluation of predictors for anatomical success in macular hole surgery in Indian
      population.
AB  - PURPOSE: The aim was to evaluate outcomes and predictors for anatomical success
      in macular hole (MH) surgery. MATERIALS AND METHODS: This was a prospective
      cohort study of patients operated for idiopathic MH with stages II, III or IV.
      Patients underwent pars plana vitrectomy with internal limiting membrane (ILM)
      peeling, internal gas tamponade, and postoperative face down positioning. The
      primary outcome measure was anatomical closure of MH, while secondary outcome
      measure was postoperative external limiting membrane (ELM) continuity. Effect of
      MH size, duration of MH, size of ILM peel, type of gas tamponade (SF6 vs. C3F8)
      and macular hole index (MHI) on anatomical MH closure was also evaluated.
      RESULTS: Of the 62 eyes operated, anatomical closure of MH was achieved in 55
      eyes (88.7%). The median duration of follow-up was 8 months (range: 6-15 months).
      Mean BVCA improved from 0.94 +/- 0.26 at baseline to 0.40 +/- 0.23 logMAR at last
      follow-up (P = 0.01). There was a statistically significant association between
      size of ILM peel and anatomical closure of MH (P = 0.04). Duration of symptoms,
      size of MH, type of gas tamponade, MHI had no effect on anatomical closure (P =
      0.22, 0.28, 0.40 respectively, Chi-square test). Postoperative continuity of the
      ELM was significantly associated with a shorter symptom duration (<6 months)
      before surgery. CONCLUSION: Acceptable anatomical closure could be attained with
      the defined technique. Size of ILM peel is a new predictor of anatomical success
      while symptom duration affects postoperative ELM continuity.

PMID- 25579359
TI  - Optical coherence tomography in papilledema and pseudopapilledema with and
      without optic nerve head drusen.
AB  - AIM: To compare the spectral domain optical coherence tomography (SD-OCT)
      findings of the optic disc and the peripapillary retina of patients with a true
      papilledema and pseudopapilledema with and without optic nerve head drusen
      (ONHD). STUDY DESIGN: Retrospective Case Control Study. SUBJECTS AND METHODS:
      Peripapillary retinal nerve fiber layer (PPRNFL) thickness as depicted by SD-OCT
      of 94 eyes of 66 patients with papilledema (30 eyes), pseudopapiledema (31 eyes),
      and normal controls (33 eyes) was analyzed. The mean RNFL thickness, total
      retinal thickness (TRT) at a superior and inferior edge of the disc and the
      quadrant wise topography of increased RNFL were compared in all three groups.
      Sensitivity, specificity, and area under the receiver operating characteristic
      curve (AROC) were calculated for all the parameters. RESULTS: The median RNFL
      thickness was 185.4 (129.5-349.3 MUm), 122.3 (109-156.3 MUm) and 91.62 +/- 7 MUm
      in papilledema, pseudopapilledema, and controls, respectively. Papilledema group
      had thicker PPRNFL in all quadrants except temporal quadrant. TRT was thicker in
      papilledema and pseudopapilledema compared to controls. ONHD could be directly
      visualized as high reflective clumps in the sub-retinal space or the RNFL in 30
      eyes. Increased RNFL thickness in all four quadrants was noted 43.3% in
      papilledema and 9.7% in pseudopapilledema. Normal RNFL thickness in all four
      quadrants was noted in 0% in papilledema and 32.3% in pseudopapilledema. Nasal
      RNFL had the highest AROC (0.792) indicating high diagnostic ability to
      differentiate papilledema from pseudopapilledema. CONCLUSION: SD-OCT can be used
      as a tool to differentiate between papilledema and pseudopapilledema.

PMID- 25579360
TI  - Development of Pocket Vision Screener and its effectiveness at screening visual
      acuity deficits.
AB  - AIM: The aim was to construct a visual acuity chart and find its effectiveness at
      screening visual acuity deficits. MATERIALS AND METHODS: Two phases were involved
      in this study.Construction of the screener: Ten Sloan letters (C, D, H, K, N, O,
      R, S, V, and Z) were selected and the letters were constructed and reduced to 0.2
      logMAR acuity size (6.92 mm) for viewing at 3 m. The screener contains three
      lines with seven letters in each. Few combinations of the seven letter sequences
      were chosen based on the row legibility scores. Three seven letter combinations
      close to the median of all combinations were selected, such that maximum
      difficulty score difference between the lines are <1%. Finding the effectiveness
      of the screener: 100 literate subjects with unaided visual acuity better than or
      equal to 6/60 were recruited for the study. Unaided visual acuity was tested
      using both the newly constructed Pocket Vision Screener and a logMAR visual
      acuity chart and the time taken to measure the visual acuity using both the
      charts was noted. RESULTS: The mean age of the subjects was 43 +/- 17 years.
      Subjects were classified as normal or deficient based on the logMAR visual acuity
      measurement. The screener was found to have 81% sensitivity, 94% specificity. The
      positive and negative predictive values were found to be 91% and 87%,
      respectively. A significant difference (P < 0.001) was found in the time taken to
      record visual acuity using both the charts. CONCLUSION: The Pocket Vision
      Screener can be used as a quick and accurate tool to screen subjects for visual
      acuity deficits, being highly sensitive, specific, and cost-effective.

PMID- 25579361
TI  - Macular function and morphology in acute retinal pigment epithelitis.
AB  - A 20-year-old man applied with vision loss in the left eye. Right eye examination
      was unremarkable. Best-corrected visual acuity (BCVA) in the left eye was 20/200.
      Fundus examination revealed a few yellow spots within a round-shaped macular
      lesion. Autofluorescence imaging showed hyperautofluorescence in the lesion.
      Central amplitudes in multifocal electroretinogram (mfERG) were depressed. The
      patient reported a rhinopharyngitis 7-10 days before the visual loss. The patient
      was diagnosed as acute retinal pigment epithelitis. BCVA improved gradually up to
      20/20 in 4 weeks. mfERG amplitudes returned to normal. A slight pigmentary
      distortion was the only residual fundus finding. 

PMID- 25579362
TI  - Linguatula serrata in the anterior chamber of the eye.
AB  - We report a case of intraocular Linguatula in healthy young female who presented
      with a history of trivial trauma, dislocated lens, inflammation and secondary
      glaucoma. A mobile worm was seen in the anterior chamber. Pars plana lensectomy
      and vitrectomy was planned to remove both the cataractous lens and the parasite
      during which the worm disappeared from view but was later recovered from the
      cassette fluid. It was identified as the nymphal form of Linguatula serrata
      (tongue worm). 

PMID- 25579363
TI  - Successful use of intravitreal and systemic colistin in treating multidrug
      resistant Pseudomonas aeruginosa post-operative endophthalmitis.
AB  - We report a case series of post-operative endophthalmitis due to Pseudomonas
      aeruginosa. A total of 8 patients operated for cataract, were referred to our
      facility with acute onset of decreased vision 1-2 days following surgery. All
      patients had clinical evidence of acute exogenous endophthalmitis with severe
      anterior chamber exudative reaction. Ocular samples (aqueous aspirate and
      vitreous tap) for microbiology were taken from all eyes. Microbiology from all
      revealed P. aeruginosa which was resistant to all antibiotics except colistin.
      With prompt and accurate microbiological support it was possible to control the
      infection in all the eyes with the use of colistin intravitreally and
      intravenously which to the best of our knowledge, has been never reported.
      Intravitreal injection of colistin could be an option effective in the management
      of multi-drug-resistant endophthalmitis caused by Gram-negative bacteria. 

PMID- 25579364
TI  - Ocular manifestations of Noonan syndrome in twin siblings: a case report of
      keratoconus with acute corneal hydrops.
AB  - Ocular manifestations of Noonan syndrome (NS) in a set of healthy 20-year-old
      African-American fraternal twins are reported with emphasis on a rare finding of
      keratoconus with acute corneal hydrops in one twin. Both the twins had learning
      disabilities and attended a special needs school. Evaluation included visual
      acuity assessment, tonometry and external eye, slit lamp and dilated fundus
      examinations, topography with Pentacam and external photographs. The first case
      was more remarkable as keratoconus with acute corneal hydrops was observed. The
      patient presented with severe cloudy vision that had worsened over a span of 1
      month. It improved significantly on follow-up. The second case included a unique
      constellation of ocular pathology that highlights the diversity of NS
      manifestations even amongst twins. Conservative treatment of keratoconus with
      acute corneal hydrops in a NS patient helped largely resolve the patient's
      condition. We report the diverse spectrum of ocular manifestations associated
      with this rare congenital disorder. 

PMID- 25579365
TI  - Comment on: Successful use of intravitreal and systemic colistin in treating
      multidrug resistant Pseudomonas aeruginosa postoperative endophthalmitis.

PMID- 25579366
TI  - Pregnancy and intraocular pressure.

PMID- 25579367
TI  - Anterior segment optical coherence tomography in angle closure glauma with
      topiramat use.

PMID- 25579368
TI  - Bilateral optic neuritis following Mycoplasma pneumoniae infection.

PMID- 25579369
TI  - Safe endoresection.

PMID- 25579370
TI  - Repeat gas insufflation for successful closure of idiopathic macular hole
      following failed primary surgery--our experience.

PMID- 25579371
TI  - E-learning in ophthalmology: where next?

PMID- 25579372
TI  - Is it really a silicone sling assisted temporalis muscle transfer?

PMID- 25579373
TI  - The unplanned intensive care unit admission.

PMID- 25579374
TI  - Once is enough: limited echocardiography in subacute shock.

PMID- 25579375
TI  - A novel DVS guidance principle and robust adaptive path-following control for
      underactuated ships using low frequency gain-learning.
AB  - Around the waypoint-based path-following control for marine ships, a novel
      dynamic virtual ship (DVS) guidance principle is developed to implement the
      assumption "the reference path is generated using a virtual ship", which is
      critical for applying the current theoretical studies in practice. Taking two
      steerable variables as control inputs, the robust adaptive scheme is proposed by
      virtue of the robust neural damping and dynamic surface control (DSC) techniques.
      The derived controller is with the advantages of concise structure and being easy
      to-implement for its burdensome superiority. Furthermore, the low frequency
      learning method improves the applicability of the algorithm. Finally, the
      comparison experiments with the line-of-sight (LOS) based fuzzy scheme are
      presented to demonstrate the effectiveness of our results. 

PMID- 25579376
TI  - Teaching how to improve activities and participation of elderly subjects: the
      carelessness of the Italian Academia shown by the national qualification for
      physiotherapists.

PMID- 25579377
TI  - A quality dietary supplement: before you start and after it's marketed--a
      conference report.
AB  - Consumers worldwide are turning to dietary supplements as one part of their
      personal goal to lead healthier and more active lives. In truth, the quality of
      life now supersedes the length of life as no one would trade living to one
      hundred (the last forty with compromised physical abilities and decreased mental
      acuity) for 80 years of travel, time with family, and intellectual pursuits. If
      there is the possibility of preventing a disease or debilitating condition
      through efficient lifestyle changes (additions, subtractions, modifications) and
      to also avoid the costly and escalating medical and pharmaceutical treatments
      that accompany having the disease/condition, then a sensible individual would
      focus on their overall health and wellness...proactively, instead of reactively.
      However, an important caveat is that over-regulation or inappropriate application
      of current regulations can increase the price of dietary supplements and
      nutritional products and thus cause underutilization of the potentially
      beneficial physiological attributes of these products. Conversely, strict
      adherence to regulatory guidelines could result in safer dietary supplements and
      fewer adverse reactions requiring medical attention. If new regulations or
      stricter interpretation/application of existing regulations result in certain
      dietary supplements being taken off the market, will continued demand create a
      completely unregulated, underground economy that will create unforeseen problems?
      More research should be supported by government agencies to determine the
      effectiveness of dietary supplements, nutritional products and complementary
      medicine in reducing personal and societal medical costs and further contribution
      to the overall health of the population. 

PMID- 25579378
TI  - Cutaneous keratoacanthomas/squamous cell carcinomas associated with
      neutralization of transforming growth factor beta by the monoclonal antibody
      fresolimumab (GC1008).
AB  - Fresolimumab is an antibody capable of neutralizing all human isoforms of
      transforming growth factor beta (TGFbeta) and has demonstrated anticancer
      activity in investigational studies. Inhibition of TGFbeta by fresolimumab can
      potentially result in the development of cutaneous lesions. The aim of this study
      was to investigate the clinical, histological, and immunohistochemical
      characteristics of cutaneous neoplasms associated with fresolimumab. Skin
      biopsies (n = 24) were collected and analyzed from patients (n = 5) with
      treatment-emergent, cutaneous lesions arising during a phase 1 study of multiple
      doses of fresolimumab in patients (n = 29) with melanoma or renal cell carcinoma.
      Blinded, independent histological review and measurements of Ki-67, p53, and HPV
      integration were performed. Based on central review, four patients developed
      lesions with histological characteristics of keratoacanthomas, and of these
      patients, a single case of well-differentiated squamous cell carcinoma was also
      found. Expression of Ki-67, no evidence of p53 overexpression, and only focal
      positivity for human papillomavirus RNA by in situ hybridization in 4/18 cases
      were consistent with these findings. Following completion of fresolimumab,
      lesions spontaneously resolved. Therefore, benign, reversible keratoacanthomas
      were the most common cutaneous neoplasms observed, a finding of importance for
      adverse event monitoring, patient care, and optimization of therapies targeting
      TGFbeta.

PMID- 25579379
TI  - Enhancement of glioma-specific immunity in mice by "NOBEL", an insulin-like
      growth factor 1 receptor antisense oligodeoxynucleotide.
AB  - Autologous glioblastoma multiforme tumor cells treated with an antisense
      oligodeoxynucleotide (AS-ODN) targeting insulin-like growth factor receptor-1
      (IGF-1R) are the basis of a vaccine with therapeutic effects on tumor recurrence
      in a pilot clinical trial. As a preface to continued clinical investigation of
      this vaccination strategy, we have studied the contribution of an optimized IGF
      1R AS-ODN, designated "NOBEL", to the induction of immunity to mouse GL261 glioma
      cells. The impact of NOBEL on mechanisms contributing to the development of GL261
      immunity was first examined in the periphery. GL261 cells are naturally
      immunogenic when implanted into the flanks of congenic C57BL/6 mice, immunizing
      rather than forming tumors in around 50 % of these animals but causing tumors in
      the majority of mice lacking T and B lymphocytes. Overnight treatment with NOBEL
      in vitro reduces IGF-1R expression by GL261 cells but has minimal effect on cell
      viability and does not reduce the capacity of the cells to form tumors upon
      implantation. In contrast, tumors are extremely rare when GL261 cells are mixed
      with NOBEL at inoculation into the flanks of C57BL/6, and the recipient mice
      become immune to subcutaneous and intracranial challenge with untreated GL261.
      Adaptive immune mechanisms contribute to this effect, as immunocompromised mice
      fail to either fully control tumor formation or develop immunity following flank
      administration of the GL261/NOBEL mix. NOBEL's structure has known
      immunostimulatory motifs that likely contribute to the immunogenicity of the mix,
      but its specificity for IGF-1R mRNA is also important as a similarly structured
      sense molecule is not effective.

PMID- 25579381
TI  - FBXW7-Induced MTOR Degradation Forces Autophagy to Counteract Persistent Prion
      Infection.
AB  - Autophagy is an important protein degradation pathway and a part of the innate
      immune system that is activated in the brain tissue during animal and human prion
      diseases. However, the possible mechanism by which prion infection triggers
      autophagy and the significance of activated autophagy on prion accumulation
      remain unknown. Here, we demonstrated that autophagic flux was enhanced in the
      persistent prion-infected cell line, SMB-S15. Knockdown of ATG5 and the presence
      of three autophagic inhibitors resulted in a significant increase of PrP(Sc). The
      mammalian target of rapamycin (MTOR) levels in SMB-S15 cells were also markedly
      decreased, in direct relation to PrP(Sc) accumulation. F-box and WD repeat domain
      containing 7 (FBXW7) levels in SMB-S15 cells and in the brains of scrapie-agent
      263K-infected hamsters were upregulated at the early stage of infection, leading
      to active ubiquitination and degradation of MTOR. Knockdown of FBXW7 in SMB-S15
      cells remarkably inhibited autophagic flux and increased PrP(Sc) accumulation.
      Thus, we conclude that prion infection induced the expression of FBXW7, which
      mediated MTOR ubiquitination and degradation, further altering phosphorylation
      status through cross talk between MTORC1 and AMPK and increasing autophagic flux.
      Autophagy may serve as innate immunity to degrade PrP(Sc) and maintain prion
      homeostasis. 

PMID- 25579380
TI  - Bee Venom Acupuncture Alleviates Experimental Autoimmune Encephalomyelitis by
      Upregulating Regulatory T Cells and Suppressing Th1 and Th17 Responses.
AB  - The protective and therapeutic mechanism of bee venom acupuncture (BVA) in
      neurodegenerative disorders is not clear. We investigated whether treatment with
      BVA (0.25 and 0.8 mg/kg) at the Zusanli (ST36) acupoints, located lateral from
      the anterior border of the tibia, has a beneficial effect in a myelin basic
      protein (MBP)(68-82)-induced acute experimental autoimmune encephalomyelitis
      (EAE) rat model. Pretreatment (every 3 days from 1 h before immunization) with
      BVA was more effective than posttreatment (daily after immunization) with BVA
      with respect to clinical signs (neurological impairment and loss of body weight)
      of acute EAE rats. Treatment with BVA at the ST36 acupoint in normal rats did not
      induce the clinical signs. Pretreatment with BVA suppressed demyelination, glial
      activation, expression of cytokines [interferon (IFN)-gamma, IL-17, IL-17A, tumor
      necrosis factor-alpha (TNF-alpha), and IL-1beta], chemokines [RANTES, monocyte
      chemotactic protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1alpha],
      and inducible nitric oxide synthase (iNOS), and activation of p38 mitogen
      activated protein kinase (MAPK) and nuclear factor (NF)-kappaB (p65 and phospho
      IkappaBalpha) signaling pathways in the spinal cord of acute EAE rats.
      Pretreatment with BVA decreased the number of CD4(+), CD4(+)/IFN-gamma(+), and
      CD4(+)/IL-17(+) T cells, but increased the number of CD4(+)/Foxp3(+) T cells in
      the spinal cord and lymph nodes of acute EAE rats. Treatment with BVA at six
      placebo acupoints (SP9, GB39, and four non-acupoints) did not have a positive
      effect in acute EAE rats. Interestingly, onset and posttreatment with BVA at the
      ST36 acupoint markedly attenuated neurological impairment in myelin
      oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE mice compared to
      treatment with BVA at six placebo acupoints. Our findings strongly suggest that
      treatment with BVA with ST36 acupoint could delay or attenuate the development
      and progression of EAE by upregulating regulatory T cells and suppressing T
      helper (Th) 17 and Th1 responses. These results warrant further investigation of
      BVA as a treatment for autoimmune disorders of the central nervous system.

PMID- 25579383
TI  - Erratum to: Activation of Glycogen Synthase Kinase-3 Mediates the Olfactory
      Deficit-Induced Hippocampal Impairments.

PMID- 25579382
TI  - Naringenin Suppresses Neuroinflammatory Responses Through Inducing Suppressor of
      Cytokine Signaling 3 Expression.
AB  - Accumulating evidence suggests that neuroinflammation is closely associated with
      the pathogenesis of neurodegenerative disorders such as Parkinson's disease and
      Alzheimer's disease. The hallmark of neuroinflammation is considered to be
      microglial activation in the central nervous system (CNS). Activated microglia
      release pro-inflammatory cytokines which cause neuroinflammation and progressive
      neuronal cell death. Therefore, inhibition of microglial activation is considered
      an important strategy in the development of neuroprotective strategy. Naringenin,
      a flavonoid found in citrus fruits and tomatoes, has been reported to have anti
      oxidant, anti-cancer, and anti-inflammatory properties. However, the mechanism of
      its beneficial anti-inflammatory effects in the CNS is poorly understood. In this
      study, we demonstrated that naringenin inhibites the release of nitric oxide
      (NO), the expression of inducible nitric oxide synthase (iNOS), and
      cyclooxygenase-2 (COX-2), as well as pro-inflammatory cytokines in microglial
      cells. Treatment of naringenin also induced suppressors of cytokine signaling
      (SOCS)-3 expression in microglia. The SOCS-3 expression and anti-inflammatory
      effects of naringenin were found to be regulated by adenosine monophosphate
      activated protein kinase alpha (AMPKalpha) and protein kinase C delta (PKCdelta).
      Besides, naringenin exerted protective property against neurotoxicity caused by
      LPS-induced microglial activation. Our findings suggest that naringenin-inhibited
      iNOS and COX-2 expression is mediated by SOCS-3 activation through AMPKalpha and
      PKCdelta signaling pathways. In a mouse model, naringenin also showed significant
      protective effects on microglial activation and improved motor coordination
      function as well. Therefore, naringenin that involves in anti-neuroinflammatory
      responses and neuroprotection might be a potential agent for treatment of
      inflammation-associated disorders.

PMID- 25579385
TI  - Myelin Lipids Inhibit Axon Regeneration Following Spinal Cord Injury: a Novel
      Perspective for Therapy.
AB  - Lack of axon regeneration following spinal cord injury has been mainly ascribed
      to the inhibitory environment of the injury site, i.e., to chondroitin sulfate
      proteoglycans (CSPGs) and myelin-associated inhibitors (MAIs). Here, we used
      shiverer (shi) mice to assess axon regeneration following spinal cord injury in
      the presence of MAIs and CSPG but in the absence of compact myelin. Although in
      vitro shi neurons displayed a similar intrinsic neurite outgrowth to wild-type
      neurons, in vivo, shi fibers had increased regenerative capacity, suggesting that
      the wild-type spinal cord contains additional inhibitors besides MAIs and CSPG.
      Our data show that besides myelin protein, myelin lipids are highly inhibitory
      for neurite outgrowth and suggest that this inhibitory effect is released in the
      shi spinal cord given its decreased lipid content. Specifically, we identified
      cholesterol and sphingomyelin as novel myelin-associated inhibitors that operate
      through a Rho-dependent mechanism and have inhibitory activity in multiple neuron
      types. We further demonstrated the inhibitory action of myelin lipids in vivo, by
      showing that delivery of 2-hydroxypropyl-beta-cyclodextrin, a drug that reduces
      the levels of lipids specifically in the injury site, leads to increased axon
      regeneration of wild-type (WT) dorsal column axons following spinal cord injury.
      In summary, our work shows that myelin lipids are important modulators of axon
      regeneration that should be considered together with protein MAIs as critical
      targets in strategies aiming at improving axonal growth following injury. 

PMID- 25579384
TI  - Crosstalk Among Disrupted Glutamatergic and Cholinergic Homeostasis and
      Inflammatory Response in Mechanisms Elicited by Proline in Astrocytes.
AB  - Hyperprolinemias are inherited disorder of proline (Pro) metabolism. Patients
      affected may present neurological manifestations, but the mechanisms of neural
      excitotoxicity elicited by hyperprolinemia are far from being understood.
      Considering that the astrocytes are important players in neurological disorders,
      the aim of the present work was to study the effects 1 mM Pro on glutamatergic
      and inflammatory parameters in cultured astrocytes from cerebral cortex of rats,
      exploring some molecular mechanisms underlying the disrupted homeostasis of
      astrocytes exposed to this toxic Pro concentration. We showed that cortical
      astrocytes of rats exposed to 1 mM Pro presented significantly elevated
      extracellular glutamate and glutamine levels, suggesting glutamate
      excitotoxicity. The excess of glutamate elicited by Pro together with increased
      glutamate uptake and upregulated glutamine synthetase (GS) activity supported
      misregulated glutamate homeostasis in astrocytic cells. High Pro levels also
      induced production/release of pro-inflammatory cytokines TNF-alpha, IL-1beta, and
      IL-6. We also evidenced misregulation of cholinergic anti-inflammatory system
      with increased acetylcholinesterase (AChE) activity and decreased acetylcholine
      (ACh) levels, contributing to the inflammatory status in Pro-treated astrocytes.
      Our findings highlighted a crosstalk among disrupted glutamate homeostasis,
      cholinergic mechanisms, and inflammatory cytokines, since ionotropic (DL-AP5 and
      CNQX) and metabotropic (MCPG and MPEP) glutamate antagonists were able to restore
      the extracellular glutamate and glutamine levels; downregulate TNFalpha and IL6
      production/release, modulate GS and AChE activities; and restore ACh levels.
      Otherwise, the non-steroidal anti-inflammatory drugs nimesulide, acetylsalicylic
      acid, ibuprofen, and diclofenac sodium decreased the extracellular glutamate and
      glutamine levels, downregulated GS and AChE activities, and restored ACh levels
      in Pro-treated astrocytes. Altogether, our results evidence that the
      vulnerability of metabolic homeostasis in cortical astrocytes might have
      important implications in the neurotoxicity of Pro.

PMID- 25579388
TI  - Striped patterns induced by delamination of drying colloidal films.
AB  - The drying of a dispersion of nanoparticles on a solid substrate can result in
      the formation of spontaneous well-ordered stripe patterns left on the substrate.
      The evaporation of solvent yields large stresses in the material which usually
      cause crack formation and delamination from the substrate. The formation of these
      stripes results from a balance between the drying stress which drives the
      delamination crack front propagation and the cohesive properties of the material.
      These solid residues arise behind the crack front and can be perpendicular or
      parallel to the front. It is then possible to inhibit these structures by
      modifying the cohesive properties of the material. This self-assembly into an
      ordered pattern can offer an efficient method to produce a patterned surface in a
      simple way. 

PMID- 25579387
TI  - Serum Uric Acid Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: a
      Systematic Review and Meta-analysis.
AB  - Previous studies suggested a possible association between serum uric acid levels
      and peripheral neuropathy in patients with type 2 diabetes, but no definite
      evidence was available. A systematic review and meta-analysis of relevant studies
      were performed to comprehensively estimate the association. Pubmed, Web of
      Science, Embase, and China Biology Medicine (CBM) databases were searched for
      eligible studies. Study-specific data were combined using random-effect or fixed
      effect models of meta-analysis according to between-study heterogeneity. Twelve
      studies were finally included into the meta-analysis, which involved a total of
      1388 type 2 diabetic patients with peripheral neuropathy and 4746 patients
      without peripheral neuropathy. Meta-analysis showed that there were obvious
      increased serum uric acid levels in diabetic patients with peripheral neuropathy
      (weighted mean difference [WMD] = 50.03 MUmol/L, 95% confidence interval [95%CI]
      22.14-77.93, P = 0.0004). Hyperuricemia was also significantly associated with
      increased risk of peripheral neuropathy in patients with type 2 diabetes (risk
      ratio [RR] = 2.83, 95%CI 2.13-3.76, P < 0.00001). Meta-analysis of two studies
      with adjusted risk estimates showed that hyperuricemia was independently
      associated with increased risk of peripheral neuropathy in type 2 diabetic
      patients (RR = 1.95, 95%CI 1.23-3.11, P = 0.005). Type 2 diabetic patients with
      peripheral neuropathy have obvious increased serum uric acid levels, and
      hyperuricemia is associated with increased risk of peripheral neuropathy. Further
      prospective cohort studies are needed to validate the impact of serum uric acid
      levels on peripheral neuropathy risk.

PMID- 25579389
TI  - 3-Keto umbilicagenin A and B, new sapogenins from Allium umbilicatum Boiss.
AB  - Two sapogenins, named 3-keto umbilicagenin A and B (1 and 2), possessing a novel
      chemical structure with a 3-keto group on the spirostane skeleton, have been
      isolated from Allium umbilicatum Boiss. Their chemical structure has been
      established through a combination of extensive spectroscopic analysis, mainly
      nuclear magnetic resonance and mass spectrometry, and chemical methods as (25R)-3
      keto-spirostan-2alpha,5alpha,6beta-triol (1) and (25R)-3-keto-spirostan
      2alpha,5alpha-diol (2). The isolated compounds were tested for cytotoxic activity
      on J-774, murine monocyte/macrophage, and WEHI-164, murine fibrosarcoma cell
      lines.

PMID- 25579390
TI  - Impact of boiling conditions on the molecular and sensory profile of a vegetable
      broth.
AB  - Low-pressure cooking has recently been identified as an alternative to ambient
      and high-pressure cooking to provide food with enhanced organoleptic properties.
      This work investigates the impact of the cooking process at different pressures
      on the molecular and sensory profile of a vegetable broth. Experimental results
      showed similar sensory and chemical profiles of vegetable broths when boiling at
      0.93 and 1.5 bar, while an enhancement of sulfur volatile compounds correlated
      with a greater leek content and savory aroma was observed when boiling at low
      pressure (80  degrees C/0.48 bar). Thus, low-pressure cooking would allow
      preserving the most labile volatiles likely due to the lower water boiling
      temperature and the reduced level of oxygen. This study evidenced chemical and
      sensory impact of pressure during cooking and demonstrated that the flavor
      profile of culinary preparations can be enhanced by applying low-pressure
      conditions.

PMID- 25579391
TI  - The role of inflammatory cytokines as key modulators of neurogenesis.
AB  - Neurogenesis is an important process in the regulation of brain function and
      behaviour, highly active in early development and continuing throughout life.
      Recent studies have shown that neurogenesis is modulated by inflammatory
      cytokines in response to an activated immune system. To disentangle the effects
      of the different cytokines on neurogenesis, here we summarise and discuss in
      vitro studies on individual cytokines. We show that inflammatory cytokines have
      both a positive and negative role on proliferation and neuronal differentiation.
      Hence, this strengthens the notion that inflammation is involved in molecular and
      cellular mechanisms associated with complex cognitive processes and, therefore,
      that alterations in brain-immune communication are relevant to the development of
      neuropsychiatric disorders. 

PMID- 25579392
TI  - Improved all-carbon spintronic device design.
AB  - The discovery of magnetism in carbon structures containing zigzag edges has
      stimulated new directions in the development and design of spintronic devices.
      However, many of the proposed structures are designed without incorporating a key
      phenomenon known as topological frustration, which leads to localized non-bonding
      states (free radicals), increasing chemical reactivity and instability. By
      applying graph theory, we demonstrate that topological frustrations can be
      avoided while simultaneously preserving spin ordering, thus providing alternative
      spintronic designs. Using tight-binding calculations, we show that all original
      functionality is not only maintained but also enhanced, resulting in the
      theoretically highest performing devices in the literature today. Furthermore, it
      is shown that eliminating armchair regions between zigzag edges significantly
      improves spintronic properties such as magnetic coupling. 

PMID- 25579393
TI  - Absence of Wolbachia endobacteria in Sri Lankan isolates of the nematode parasite
      of animals Setaria digitata.
AB  - Setaria digitata is an animal filarial parasite with natural hosts of cattle and
      buffaloes that causes mild disease conditions. Infection of non-permissive hosts
      such as goats, sheep and horses, by this nematode can cause cerebrospinal
      nematodiasis that leads to lumbar paralysis and the eventual death of the animals
      and inflicts considerable economic losses on livestock farmers. Wolbachia are
      obligate mutualistic endosymbionts for some filarial nematodes and are currently
      being targeted for the control of diseases caused by these parasites. However,
      little is known about the occurrence of this endosymbiont in the Setariidae
      family. In this work, worms collected from infected cattle in Sri Lanka were
      morphologically identified as S. digitata and tested for the presence of
      Wolbachia by PCR screening using the WSP- and Wolbachia-specific 16S rRNA and
      multilocus sequence typing primers that were designed to amplify the gatB, coxA,
      hcpA, ftsZ and fbpA sequences of Wolbachia. The presence of endobacteria in S.
      digitata was also examined by whole-mount immunofluorescence staining of the
      parasites and transmission electron microscopic studies. These analyses did not
      produce evidence of presence of Wolbachia or any other endosymbiotic bacteria in
      S. digitata, whereas such evidence was found in Brugia malayi, which was used as
      a positive control in this study. 

PMID- 25579386
TI  - Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl
      CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin
      Repair Involved in the Treatment of Multiple Sclerosis (MS).
AB  - Multiple sclerosis (MS) is a chronic progressive, neurological disease
      characterized by the targeted immune system-mediated destruction of central
      nervous system (CNS) myelin. Autoreactive CD4+ T helper cells have a key role in
      orchestrating MS-induced myelin damage. Once activated, circulating Th1-cells
      secrete a variety of inflammatory cytokines that foster the breakdown of blood
      brain barrier (BBB) eventually infiltrating into the CNS. Inside the CNS, they
      become reactivated upon exposure to the myelin structural proteins and continue
      to produce inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha)
      that leads to direct activation of antibodies and macrophages that are involved
      in the phagocytosis of myelin. Proliferating oligodendrocyte precursors (OPs)
      migrating to the lesion sites are capable of acute remyelination but unable to
      completely repair or restore the immune system-mediated myelin damage. This
      results in various permanent clinical neurological disabilities such as cognitive
      dysfunction, fatigue, bowel/bladder abnormalities, and neuropathic pain. At
      present, there is no cure for MS. Recent remyelination and/or myelin repair
      strategies have focused on the role of the neurotrophin brain-derived
      neurotrophic factor (BDNF) and its upstream transcriptional repressor methyl CpG
      binding protein (MeCP2). Research in the field of epigenetic therapeutics
      involving histone deacetylase (HDAC) inhibitors and lysine acetyl transferase
      (KAT) inhibitors is being explored to repress the detrimental effects of MeCP2.
      This review will address the role of MeCP2 and BDNF in remyelination and/or
      myelin repair and the potential of HDAC and KAT inhibitors as novel therapeutic
      interventions for MS. 

PMID- 25579394
TI  - Further thoughts on the taxonomy and vector role of Rhipicephalus sanguineus
      group ticks.
AB  - Rhipicephalus sanguineus is a tick species described in 1806 by Latreille, based
      on specimens probably collected in France. However, this is a taxon with
      uncertain morphological definition and recent studies have gathered irrefutable
      evidence supporting the existence of a cryptic species-complex under the name 'R.
      sanguineus', whose number of sibling species around the world has yet to be
      ascertained. This fact is of great medical and veterinary concern, also
      considering that ticks currently identified as 'R. sanguineus' have been regarded
      as proven or putative vectors of several pathogens infecting dogs and humans.
      Differences in the distribution and prevalence of some of these microorganisms
      (e.g., Ehrlichia canis and Hepatozoon canis) further support the existence of
      distinct species under the name 'R. sanguineus' and suggest that the vector
      competence of these tick species may vary. This article provides an account on
      the taxonomy and the vector role of ticks belonging to the R. sanguineus group in
      the light of recent research. 

PMID- 25579395
TI  - Evaluation of 'best practice' (SCOPS) guidelines for nematode control on
      commercial sheep farms in England and Wales.
AB  - Parasitic diseases are a major constraint to optimum livestock production and are
      the major cause of economic loss in UK sheep flocks, with farmers remaining
      dependant on anthelmintics for control. In the UK, research and evidence based,
      "best practice" guidelines for sustainable control of parasites in sheep (SCOPS)
      were first produced in 2004 and have been regularly updated since. This study was
      designed to evaluate the effect of these best practice guidelines for worm
      control on lamb production and infection levels, compared with more traditional
      management. Sixteen farms were selected based on a 2 cube factorial design with 3
      factors known to affect worm epidemiology: control regimen; farm type; and
      climatic region. A formalised plan for worm control using 7 potential resistance
      delaying practices was prepared for each of the 8 best practice (SCOPS) farms, in
      conjunction with the farms veterinarians. The 8 farms in the traditional
      management group (CONTROL farms) were selected based on ongoing evidence of them
      using worm control strategies deemed to be "higher-risk". A cohort of 40-50 study
      lambs at each farm was monitored from birth to finishing, allowing evaluation of
      lamb productivity, worm infection levels and for comparison of numbers of
      anthelmintic treatments. Birth and mid-season weights were used to calculate
      daily live-weight gain. Birth and finish dates were used to calculate time to
      finish and finish weights were also compared. Faecal egg counts, larval culture
      and species differentiation were undertaken throughout the year to assess the
      impact of the control strategies on worm burdens. There was no significant
      difference in results for any of the 3 production responses when comparing
      predicted means accounting for the differences in birth weight. In fact SCOPS
      farms had, on average, a higher daily weight gain and finish weight than CONTROL
      farms when comparing observed means. Statistical analysis of infection levels
      clearly showed no significant effect according to farm type (p=0.71) or treatment
      (p=0.81). In contrast the effect of region (p=0.08), although not significant,
      had a much larger effect size (standardised mean difference) with lower parasite
      burdens based on faecal egg counts on Northern farms compared to Southern farms.
      For both ewes and lambs, significantly fewer treatments were carried out on the
      SCOPS farms. The data collected from this study suggests that farms implementing
      SCOPS principles use less anthelmintic than other farms, without loss of animal
      performance or increased worm burden. 

PMID- 25579396
TI  - A vaccine formulation combining rhoptry proteins NcROP40 and NcROP2 improves pup
      survival in a pregnant mouse model of neosporosis.
AB  - Currently there are no effective vaccines for the control of bovine neosporosis.
      During the last years several subunit vaccines based on immunodominant antigens
      and other proteins involved in adhesion, invasion and intracellular proliferation
      of Neospora caninum have been evaluated as targets for vaccine development in
      experimental mouse infection models. Among them, the rhoptry antigen NcROP2 and
      the immunodominant NcGRA7 protein have been assessed with varying results. Recent
      studies have shown that another rhoptry component, NcROP40, and NcNTPase, a
      putative dense granule antigen, exhibit higher expression levels in tachyzoites
      of virulent N. caninum isolates, suggesting that these could be potential vaccine
      candidates to limit the effects of infection. In the present work, the safety and
      efficacy of these recombinant antigens formulated in Quil-A adjuvant as
      monovalent vaccines or pair-wise combinations (rNcROP40+rNcROP2 and
      rNcGRA7+rNcNTPase) were evaluated in a pregnant mouse model of neosporosis. All
      the vaccine formulations elicited a specific immune response against their
      respective native proteins after immunization. Mice vaccinated with rNcROP40 and
      rNcROP2 alone or in combination produced the highest levels of IFN-gamma and
      exhibited low parasite burdens and low IgG antibody levels after the challenge.
      In addition, most of the vaccine formulations were able to increase the median
      survival time in the offspring. However, pup survival only ensued in the groups
      vaccinated with rNcROP40+rNcROP2 (16.2%) and rNcROP2 (6.3%). Interestingly,
      vertical transmission was not observed in those survivor pups immunized with
      rNcROP40+rNcROP2, as shown by PCR analyses. These results show a partial
      protection against N. caninum infection after vaccination with rNcROP40+rNcROP2,
      suggesting a synergistic effect of the two recombinant rhoptry antigens. 

PMID- 25579397
TI  - A comparison of the FECPAK and Mini-FLOTAC faecal egg counting techniques.
AB  - Faecal egg counts (FECs) are used for detecting and quantifying nematode
      infections and are the basis for determining drug efficacy and anthelmintic
      resistance in faecal egg count reduction tests (FECRTs). Currently, several FEC
      techniques are available for detecting and quantifying eggs of sheep nematodes. A
      comparison of the egg counts from the FECPAK (with a minimum detection limit of
      30 eggs per gram (epg)) and Mini-FLOTAC (with a minimum detection limit of 5 epg)
      showed better diagnostic performance with Mini-FLOTAC in terms of measurement
      error (level of over- or under-estimation of FEC) and precision (variability in
      FEC). A tendency to under-estimate FEC was observed with the FECPAK particularly
      at egg densities of less than 500 epg. It is concluded that Mini-FLOTAC is a
      reliable diagnostic tool offering reduced measurement error and a higher level of
      precision. 

PMID- 25579398
TI  - Relevance of presynaptic actin dynamics for synapse function and mouse behavior.
AB  - Actin is the most abundant cytoskeletal protein in presynaptic terminals as well
      as in postsynaptic dendritic spines of central excitatory synapses. While the
      relevance of actin dynamics for postsynaptic plasticity, for instance activity
      induced changes in dendritic spine morphology and synaptic glutamate receptor
      mobility, is well-documented, only little is known about its function and
      regulatory mechanisms in presynaptic terminals. Moreover, studies on presynaptic
      actin dynamics have often been inconsistent, suggesting that actin has diverse
      presynaptic functions, varying likely between specific types of excitatory
      synapses and/or their activity states. In this review, we will summarize and
      discuss the function and upstream regulatory mechanisms of the actin cytoskeleton
      in presynaptic terminals, focusing on excitatory synapses of the mammalian
      central nervous system. Due to length restrictions we will mainly concentrate on
      new insights into actin's presynaptic function that have been gained by cell
      biological and mouse genetic approaches since the excellent 2008 review by
      Cingolani and Goda.

PMID- 25579399
TI  - Solvation shell resolved THz spectra of simple aqua ions - distinct distance- and
      frequency-dependent contributions of solvation shells.
AB  - Hydration of ions is a topic of broad relevance in chemistry and biology. Liquid
      state terahertz spectroscopy has been demonstrated to be able to detect even
      small solute-induced changes in the hydrogen bond network dynamics at the solute
      water interface. Here, we apply ab initio molecular dynamics simulations to study
      the solvation of Na(+) and Cl(-) in bulk water in the context of their far
      infrared responses. Spatial decomposition schemes for infrared spectra down to
      the THz regime reveal the importance of both dipolar couplings and correlations
      in particle motion in these aqueous solutions. The explicit representation of the
      electronic structure properly captures the solute-solvent polarization effects
      that are crucial for the interpretation of recent experimental data. This
      demonstrates that theoretical spectroscopy significantly complements experimental
      measurements and provides most detailed insights by selectively monitoring the
      spectral activity due to distinct hydration spheres. 

PMID- 25579400
TI  - Retraction: Baicalin induced dendritic cell apoptosis in vitro.
AB  - [This retracts the article on p. 15 in vol. 2, PMID: 21687510.]. 

PMID- 25579402
TI  - Uncertainty evaluation of the diffusive gradients in thin films technique.
AB  - Although the analytical performance of the diffusive gradients in thin films
      (DGT) technique is well investigated, there is no systematic analysis of the DGT
      measurement uncertainty and its sources. In this study we determine the
      uncertainties of bulk DGT measurements (not considering labile complexes) and of
      DGT-based chemical imaging using laser ablation - inductively coupled plasma mass
      spectrometry. We show that under well-controlled experimental conditions the
      relative combined uncertainties of bulk DGT measurements are ~10% at a confidence
      interval of 95%. While several factors considerably contribute to the uncertainty
      of bulk DGT, the uncertainty of DGT LA-ICP-MS mainly depends on the signal
      variability of the ablation analysis. The combined uncertainties determined in
      this study support the use of DGT as a monitoring instrument. It is expected that
      the analytical requirements of legal frameworks, for example, the EU Drinking
      Water Directive, are met by DGT sampling.

PMID- 25579403
TI  - Quantitative proteomic analysis of sub-MIC erythromycin inhibiting biofilm
      formation of S. suis in vitro.
AB  - Streptococcus suis (S. suis) is a swine pathogen and also a zoonotic agent.
      Biofilms of S. suis may cause persistent infections by the host immune system and
      antibiotics. Sub-minimal inhibitory concentration (sub-MIC) of erythromycin can
      inhibit biofilm formation in bacteria. Here, we performed comparative proteomic
      analyses of cells at two different conditions: sub-MIC erythromycin treated and
      nontreated cells. Using iTRAQ strategy, we found some novel proteins that
      involved in biofilm formation. 79 differentially expressed proteins were
      identified in sub-MIC erythromycin inhibiting planktonic cell when the protein
      had both a fold-change of more that a ratio >1.2 or <0.8 (p-value <0.05). Several
      cell surface proteins (such as Primosomal protein N', l-fucose isomerase, and ABC
      superfamily ATP binding cassette transporter, membrane protein), as well as those
      involved in Quorum-sensing, were found to be implicated in biofilm formation.
      Overall, our results indicated that cell surface proteins played an important
      role in biofilm formation. Quorum-sensing played a crucial role leading to
      biofilm formation. ABC superfamily ATP binding cassette transporter, membrane
      protein and comD might act as channels for erythromycin uptake in Quorum-sensing
      system. Thus, our data analyzed rough regulatory pathways of biofilm formation
      that might potentially be exploited to deal with biofilm infections of S. suis.
      This article is part of a Special Issue entitled: Microbial Proteomics.
      BIOLOGICAL SIGNIFICANCE: In this study, we identified many proteins involved in
      cell transport, biological regulation and signal transduction, stress responses
      and other metabolic processes that were not previously known to be associated
      with biofilm formation of S. suis and target spot of erythromycin. Therefore, our
      manuscript represents the most comprehensive analysis of protein profiles of
      biofilm formation of S. suis inhibited by sub-MIC erythromycin and provides new
      proteomic information about biofilm formation.

PMID- 25579404
TI  - Comparative secretome analysis of rat stomach under different nutritional status.
AB  - Obesity is a major public health threat for many industrialised countries.
      Bariatric surgery is the most effective treatment against obesity, suggesting
      that gut derived signals are crucial for energy balance regulation. Several
      descriptive studies have proven the presence of gastric endogenous systems that
      modulate energy homeostasis; however, these systems and the interactions between
      them are still not well known. In the present study, we show for the first time
      the comparative 2-DE gastric secretome analysis under different nutritional
      status. We have identified 38 differently secreted proteins by comparing stomach
      secretomes from tissue explant cultures of rats under feeding, fasting and re
      feeding conditions. Among the proteins identified, glyceraldehyde-3-phosphate
      dehydrogenase was found to be more abundant in gastric secretome and plasma after
      re-feeding, and downregulated in obesity. Additionally, two calponin-1 species
      were decreased in feeding state, and other were modulated by nutritional and
      metabolic conditions. These and other secreted proteins identified in this work
      may be considered as potential gastrokines implicated in food intake regulation.
      BIOLOGICAL SIGNIFICANCE: The present work has an important impact in the field of
      obesity, especially in the regulation of body weight maintenance by the stomach.
      Nowadays, the most effective treatment in the fight against obesity is bariatric
      surgery, which suggests that stomach derived signals might be crucial for the
      regulation of the energy homeostasis. However, until now, the knowledge about the
      gastrokines and its mechanism of action has been poorly elucidated. In the
      present work, we had updated a previously validated explant secretion model for
      proteomic studies; this analysis allowed us, for the first time, to study the
      gastric secretome without interferences from other organs. We had identified 38
      differently secreted proteins comparing ex vivo cultured stomachs from rats under
      feeding, fasting and re-feeding regimes. The results in the present article
      provide novel targets to study the role of the stomach in body weight and
      appetite regulation, and suggest new potential therapeutic targets for treating
      obesity.

PMID- 25579411
TI  - Storage, transport, release: heme versatility in nitrite reductase electron
      transfer studied by molecular dynamics simulations.
AB  - Using molecular dynamics simulations of the thermodynamic integration type, we
      study the energetics and kinetics of electron transfer through the nitrite
      reductase enzyme of Sulfurospirillum deleyianum, Wolinella succinogenes and
      Campylobacter jejuni. In all of these five-heme proteins, the storage of an even
      number of electrons within a monomeric chain is thermodynamically favoured.
      Kinetically, two of these electrons are usually transferred almost simultaneously
      towards the active site. Although the free energy landscape for charge transfer
      varies significantly from organism to organism, the heme cofactor closest to the
      interface of a protein dimer always exhibits a particularly low free energy,
      suggesting that protein dimerization is functional. Interheme electron
      interaction effects do not play a significant role. 

PMID- 25579412
TI  - A plea for rational mitigation of poor outcomes in the 'off-label use' of
      medications for the management of pain.
AB  - Neuropathic pain is a common and difficult to manage public health problem
      characterized by frequent treatment failure and high management costs. The
      variable presentation and response to treatment among patients make it difficult
      for physicians to apply a single, standardized approach for management. The
      physician's role in treating neuropathic pain is complex. Clinical decisions must
      be drawn from personal and shared experience, case reports, and evidence-based,
      controlled trials performed on selected populations of patients with common,
      narrowly-defined conditions. Recent advances in our understanding of the
      mechanisms that underlie the processing of nociceptive stimuli and the perception
      of pain have led to the increased 'off-label use' of adjuvant medications in an
      attempt to provide relief for many patients who heretofore have suffered
      unnecessarily with intractable neuropathic pain. Unfortunately, as with any
      treatment, sound clinical decisions can occasionally result in an untoward
      adverse response. It is therefore imperative that potential adverse effects
      inherent to all medications be considered and weighed against the untoward
      consequences of withholding treatment prior to incorporating their use in any
      course of management. This commentary presents a case report that illustrates a
      particularly devastating consequence that was encountered when a medication was
      selected for 'off-label use' in the treatment of intractable pain and presents an
      opinion for consideration in developing guidelines for determining acceptable
      risk and standard of care based upon rational adherence or deviation from the
      approved indications offered for the use of a medication at the time of its
      introduction into practice is granted. 

PMID- 25579413
TI  - Pretreatment with intravenous levetiracetam in the rhesus monkey Coriaria lactone
      induced status epilepticus model.
AB  - PURPOSE: To investigate the antiepileptic and protective effects of intravenous
      levetiracetam (iv LEV) in the rhesus monkey model of acute status epilepticus
      (SE). METHODS: Thirty minutes before intraperitoneal induction of SE by Coriaria
      lactone (CL), rhesus monkeys were treated with LEV (15 or 150 mg/kg) delivered
      intravenously as a single bolus. CL dose and epileptic behavior were recorded.
      Electroencephalography (EEG) was performed before and during the experiment. All
      rhesus monkeys were killed after 1-month video monitoring and processed for
      pathological investigation of neuronal injury, terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labeling (TUNEL) staining, and glial
      fibrillary acidic protein (GFAP) staining. RESULTS: No animal exhibited
      spontaneous seizures during 1-month video monitoring. Development of acute SE was
      significantly inhibited in the group given 150 mg/kg LEV, compared with controls
      and the 15 mg/kg LEV group. Delayed latency, reduction of SE duration, decreased
      cumulative time of tonic convulsions, slight severity of SE, and a high CL
      induction dose were observed in the high LEV dose group (p<0.05). The EEG showed
      less frequent epileptic discharges in the group administered with 150 mg/kg LEV.
      Hematoxylin and eosin (H&E) staining, ultrastructural examination, TUNEL and GFAP
      staining revealed serious damage, including neuron loss, swollen mitochondrion,
      and strong positivity for TUNEL in the hippocampus and thalamus of controls,
      whereas moderate damage in the group administered with 15 mg/kg LEV, and very
      mild damage in the 150 mg/kg LEV group. Gliosis was found in the hippocampus of
      controls, not in the LEV groups and normal rhesus monkey. CONCLUSION: The study
      supports the antiepileptic and protective effect of pretreatment with intravenous
      LEV in rhesus monkey model with SE.

PMID- 25579414
TI  - Transcranial direct current stimulation in the prophylactic treatment of migraine
      based on interictal visual cortex excitability abnormalities: A pilot randomized
      controlled trial.
AB  - PURPOSE: The aims of this paper are (i) to compare the excitability of visual
      cortex in migraine patients with healthy volunteers; and (ii) if an abnormal
      excitability has been found, to modulate cortical excitability in migraine
      patients with transcranial direct current stimulation (tDCS) and observe their
      clinical and neurophysiological effects. METHODS: The study was divided into two
      steps. A cross-sectional study (step 1) was conducted to compare the cortical
      excitability of 23 migraineurs (11 with and 12 without aura) on 11 healthy
      individuals. On step 2, a randomized, double blinded, controlled pilot trial was
      carried on with 19 migraineurs, randomly divided into: experimental and control
      group. During 12 sessions, experimental and group received active tDCS to visual
      cortex and control group received sham tDCS. The headache diary was applied for a
      total of 90days (before, during and after tDCS sessions). Phosphene threshold
      (PT) induced by transcranial magnetic stimulation was recorded to measure the
      excitability of the visual cortex before and after each session. RESULTS: Step 1
      showed higher level of cortical excitability between migraineurs when compared to
      healthy volunteers; therefore, cathodal tDCS was applied over visual cortex in
      step 2. After tDCS application, a significant decrease was observed in a number
      of migraine attacks, painkiller intake and duration of each attack just in
      experimental group. The analysis of PT indicated no difference in cortical
      excitability after tDCS. CONCLUSIONS: Findings of the study suggested that
      inhibitory tDCS on visual cortex might be an alternative and non-pharmacological
      treatment for migraine prophylaxis. However the clinical improvements of patients
      after tDCS treatment are not correlated with changes in cortical excitability.

PMID- 25579415
TI  - Terahertz intersublevel transitions in single self-assembled InAs quantum dots
      with variable electron numbers.
AB  - We propose a method for performing terahertz spectroscopy on nanometer (nm)-scale
      systems by using metal nanogap electrodes. Intersublevel transition spectra of
      single self-assembled InAs quantum dots (QDs) have been measured with high
      signal/noise ratios by using a single electron transistor geometry that consists
      of a QD and nanogap metal electrodes as a terahertz detector. Photocurrent
      distribution with respect to the Coulomb diamonds indicates that there are two
      mechanisms for the photocurrent generation. When the p shell was fully occupied,
      we observed rather simple photocurrent spectra induced by the p -> d transitions.
      However, when the p shell was half-filled, the photocurrent spectra exhibited a
      markedly different behavior, which we attribute to the fluctuation in electron
      configuration when the empty p state is filled back from the electrodes. 

PMID- 25579423
TI  - Decompression and paraspinous tension band: a novel treatment method for patients
      with lumbar spinal stenosis and degenerative spondylolisthesis.
AB  - BACKGROUND CONTEXT: Prior studies have demonstrated the superiority of
      decompression and fusion over decompression alone for the treatment of lumbar
      degenerative spondylolisthesis with spinal stenosis. More recent studies have
      investigated whether nonfusion stabilization could provide durable clinical
      improvement after decompression and fusion. PURPOSE: To examine the clinical
      safety and effectiveness of decompression and implantation of a novel flexion
      restricting paraspinous tension band (PTB) for patients with degenerative
      spondylolisthesis. STUDY DESIGN: A prospective clinical study. PATIENT SAMPLE:
      Forty-one patients (7 men and 34 women) aged 45 to 83 years (68.2 +/- 9.0) were
      recruited with symptomatic spinal stenosis and Meyerding Grade 1 or 2
      degenerative spondylolisthesis at L3-L4 (8) or L4-L5 (33). OUTCOME MEASURES: Self
      reported measures included visual analog scale (VAS) for leg, back, and hip pain
      and the Oswestry Disability Index (ODI). Physiologic measures included
      quantitative and qualitative radiographic analysis performed by an independent
      core laboratory. METHODS: Patients with lumbar degenerative spondylolisthesis and
      stenosis were prospectively enrolled at four European spine centers with
      independent monitoring of data. Clinical and radiographic outcome data collected
      preoperatively were compared with data collected at 3, 6, 12, and 24 months after
      surgery. This study was sponsored by the PTB manufacturer (Simpirica Spine, Inc.,
      San Carlos, CA, USA), including institutional research support grants to the
      participating centers totaling approximately US $172,000. RESULTS: Statistically
      significant improvements and clinically important effect sizes were seen for all
      pain and disability measurements. At 24 months follow-up, ODI scores were reduced
      by an average of 25.4 points (59%) and maximum leg pain on VAS by 48.1 mm (65%).
      Back pain VAS scores improved from 54.1 by an average of 28.5 points (53%). There
      was one postoperative wound infection (2.4%) and an overall reoperation rate of
      12%. Eighty-two percent patients available for 24 months follow-up with a PTB in
      situ had a reduction in ODI of greater than 15 points and 74% had a reduction in
      maximum leg pain VAS of greater than 20 mm. According to Odom criteria, most of
      these patients (82%) had an excellent or good outcome with all except one patient
      satisfied with surgery. As measured by the independent core laboratory, there was
      no significant increase in spondylolisthesis, segmental flexion-extension range
      of motion, or translation and no loss of lordosis in the patients with PTB at the
      2 years follow-up. CONCLUSIONS: Patients with degenerative spondylolisthesis and
      spinal stenosis treated with decompression and PTB demonstrated no progressive
      instability at 2 years follow-up. Excellent/good outcomes and significant
      improvements in patient-reported pain and disability scores were still observed
      at 2 years, with no evidence of implant failure or migration. Further study of
      this treatment method is warranted to validate these findings.

PMID- 25579424
TI  - N-Cadherin-mediated cell adhesion is regulated by extracellular Zn(2+).
AB  - Synapses in the central nervous system (CNS) are highly dynamic structures that
      undergo reorganisation in response to synaptic activity. Dysfunctional structural
      synaptic plasticity is associated with impaired brain function and several
      neurological disorders. As response to synaptic activity, dendritic spines of
      excitatory synapses were reported to undergo alterations in their molecular
      structure and morphology leading to increased postsynaptic density size and spine
      volume. For these structural changes a transient activity-dependent weakening of
      synaptic adhesion will be necessary. Here, we report that zinc can modulate N
      cadherin-mediated adhesion. Quantification of binding activity was performed
      using laser tweezer technique. Our results show that increased levels of zinc
      abolished N-cadherin binding without altering the number of N-cadherin molecules
      expressed at the cell surface. Furthermore, zinc directly interacted with N
      cadherin and the regulatory role was found to take place under physiological zinc
      concentrations within minutes. Given that zinc is released at zincergic synapses
      in the CNS, our findings may contribute to mechanistic insights in the interplay
      between zinc signalling, activation of glutamate receptors and downstream
      pathways, and the coordination of pre- and postsynaptic changes via trans
      synaptic cell adhesion complexes, all finally contributing to synaptic
      plasticity. 

PMID- 25579425
TI  - Seasonal variation in wing size and shape between geographic populations of the
      malaria vector, Anopheles coluzzii in Burkina Faso (West Africa).
AB  - The mosquito, Anopheles coluzzii is a major vector of human malaria in Africa
      with widespread distribution throughout the continent. The species hence
      populates a wide range of environments in contrasted ecological settings often
      exposed to strong seasonal fluctuations. In the dry savannahs of West Africa,
      this mosquito population dynamics closely follows the pace of surface water
      availability: the species pullulates during the rainy season and is able to
      reproduce throughout the dry season in areas where permanent water bodies are
      available for breeding. The impact of such environmental fluctuation on mosquito
      development and the phenotypic quality of emerging adults has however not been
      addressed in details. Here, we examined and compared phenotypic changes in the
      duration of pre-imaginal development, body dry mass at emergence and wing size,
      shape and surface area in young adult females An. coluzzii originated from five
      distinct geographic locations when they are reared in two contrasting conditions
      mimicking those experienced by mosquitoes during the rainy season (RS) and at the
      onset of the dry season (ODS) in Burkina Faso (West Africa). Our results
      demonstrated strong phenotypic plasticity in all traits, with differences in the
      magnitude and direction of changes between RS and ODS depending upon the
      geographic origin, hence the genetic background of the mosquito populations.
      Highest heterogeneity within population was observed in Bama, where large
      irrigation schemes allow year-round mosquito breeding. Further studies are needed
      to explore the adaptive value of such phenotypic plasticity and its relevance for
      local adaptation in An. coluzzii. 

PMID- 25579426
TI  - Trypanosoma cruzi infection in Triatoma sordida before and after community-wide
      residual insecticide spraying in the Argentinean Chaco.
AB  - Triatoma sordida is a secondary vector of Trypanosoma cruzi in the Gran Chaco and
      Cerrado eco-regions where it frequently infests peridomestic and domestic
      habitats. In a well-defined area of the humid Argentine Chaco, very few T.
      sordida were found infected when examined by optical microscopic examination
      (OM). In order to further assess the role of T. sordida and the relative
      magnitude of subpatent bug infections, we examined the insects for T. cruzi
      infection, parasite Discrete Typing Units (DTUs) and bloodmeal sources using
      various molecular techniques. Among 205 bugs with a negative or no OM-based
      diagnosis, the prevalence of infection determined by kDNA-PCR was nearly the same
      in bugs captured before (6.3%) and 4 months after insecticide spraying (6.4%). On
      average, these estimates were sixfold higher than the prevalence of infection
      based on OM (1.1%). Only TcI was identified, a DTU typically associated with
      opossums and rodents. Chickens and turkeys were the only bloodmeal sources
      identified in the infected specimens and the main local hosts at the bugs'
      capture sites. As birds are refractory to T. cruzi infection, further studies are
      needed to identify the infectious bloodmeal hosts. The persistent finding of
      infected T. sordida after community-wide insecticide spraying highlights the need
      of sustained vector surveillance to effectively prevent T. cruzi transmission in
      the domestic and peridomestic habitats. 

PMID- 25579428
TI  - Inhibition of human efflux transporter ABCC2 (MRP2) by self-emulsifying drug
      delivery system: influences of concentration and combination of excipients.
AB  - PURPOSE: This study investigated influences of concentration and combination of
      excipients, commonly used in self-emulsifying drug delivery systems (SEDDS), on
      inhibition of human efflux transporter ABCC2 (MRP2). METHODS: Ten commonly used
      excipients of SEDDS with inhibitory effect on MRP2 including Cremophor(r) EL,
      Cremophor(r) RH, Pluronic(r) F127, Maisine(r) 35-1, beta-cyclodextrin,
      Labrasol(r), Pluronic(r) F68, PEG 2000, PEG 400 and Transcutol(r) were studied
      with the Caco-2 cell model. Six excipients with inhibitory effect including
      Cremophor(r) EL, Cremophor(r) RH, Pluronic(r) F127, PEG 2000, PEG 400 and
      Transcutol(r) were further analyzed using the MRP2 vesicle assay and ATPase
      activity assay. Ultra-performance liquid-chromatography tandem mass spectrometry
      was used to measure scutellarin as the MRP2 substrate. RESULTS: In studying
      concentration-dependent effects, five excipients including Cremophor(r) EL,
      Cremophor(r) RH, Pluronic(r) F127, Maisine(r) 35-1 and beta-cyclodextrin showed
      concentration-dependent decrease in efflux ratio of scutellarin. The other five
      excipients did not show such phenomenon, and their inhibitory effects were
      restricted to be above to certain critical or minimum concentrations. In studying
      combined effects, PEG 2000 and Pluronic(r) F127 both showed combined effect with
      Cremophor(r) EL on inhibiting MRP2. However, some combinations of excipients such
      as PEG 400 and Transcutol(r) with Cremophor(r) EL increased the scutellarin
      efflux ratio and decreased the transport of scutellarin and ATPase activity,
      compared to Cremophor(r) EL alone. CONCLUSION: The above results suggest that
      appropriate choice of excipients according to their concentration-dependent and
      combined effects on MRP2 inhibition can facilitate formulation of SEDDS for
      improving the bioavailability of drugs that are MRP2 substrates.

PMID- 25579429
TI  - Poly[N-(2-aminoethyl)ethyleneimine] as a new non-viral gene delivery carrier: the
      effect of two protonatable nitrogens in the monomer unit on gene delivery
      efficiency.
AB  - PURPOSE: The aim of this study was to investigate the in vitro gene delivery
      efficiency of poly[N-(2-aminoethyl)ethylene-imine](PAEEI), a polymer with a
      linear Polyethyleneimine (LPEI) backbone and with aminoethyl side groups that has
      two protonatable nitrogen atoms per monomer unit instead of one as in LPEI (an
      established gene delivery polymer). Method. PAEEI (Mn=4.5 kDa, Mw= 10 kDa) was
      synthesized by ring-opening polymerization of N-(2-(1'-aziridino)ethyl)formamide
      followed by hydrolysis of the amide groups. The buffering capacity of the
      resulting polymer was determined by acid-base titration and consequently the
      percentage of the protonated nitrogen atoms was calculated. Polyplexes were
      prepared separately in buffers with different ionic strength including Hepes
      buffered saline (150 mM NaCl) and Hepes buffered glucose (5% glucose) and their
      zeta-potential, hydrodynamic diameter and colloidal stability were measured.
      Transfection activity (and toxicity in Hela cells) of the polyplexes were done in
      HeLa, CHO and HEK293T cells. Cell incubations with polyplexes were done both in
      the presence and absence (HeLa cells) of serum. Results. PAEEEI showed two times
      more buffering capacity than LPEI. PAEEI-based Polyplexes had about the same size
      and zeta-potential as those of LPEI, with a higher colloidal stability in saline
      buffer in continuous particle size measurement. Their transfection activity was
      slightly higher than 22-kDa LPEI polyplexes whereas their toxicity profiles were
      similar in cell lines studied. The PAEEI polyplexes showed gene expression
      activity both in the presence and absence of serum. Conclusion. Paying attention
      to the fact that LPEI molecules with smaller sizes than 22 kDa show less
      transfection efficiency than LPEI 22, the effect of smaller size of PAEEI (10
      kDa) on the gene delivery efficiency was compensated by its higher buffering
      capacity due to carrying more protonatable nitrogen per monomeric unit comparing
      with LPEI (22 kDa). Having slightly higher transfection efficiency and better
      colloidal stability than PEI-based systems, PAEEI is an attractive candidate for
      future in vivo gene delivery studies.

PMID- 25579427
TI  - Myeloid cell-derived reactive oxygen species externally regulate the
      proliferation of myeloid progenitors in emergency granulopoiesis.
AB  - The cellular mechanisms controlling infection-induced emergency granulopoiesis
      are poorly defined. Here we found that reactive oxygen species (ROS)
      concentrations in the bone marrow (BM) were elevated during acute infection in a
      phagocytic NADPH oxidase-dependent manner in myeloid cells. Gr1(+) myeloid cells
      were uniformly distributed in the BM, and all c-kit(+) progenitor cells were
      adjacent to Gr1(+) myeloid cells. Inflammation-induced ROS production in the BM
      played a critical role in myeloid progenitor expansion during emergency
      granulopoiesis. ROS elicited oxidation and deactivation of phosphatase and tensin
      homolog (PTEN), resulting in upregulation of PtdIns(3,4,5)P3 signaling in BM
      myeloid progenitors. We further revealed that BM myeloid cell-produced ROS
      stimulated proliferation of myeloid progenitors via a paracrine mechanism. Taken
      together, our results establish that phagocytic NADPH oxidase-mediated ROS
      production by BM myeloid cells plays a critical role in mediating emergency
      granulopoiesis during acute infection. 

PMID- 25579430
TI  - Organic anion transporting polypeptides 1B1 and 1B3 play an important role in
      uremic toxin handling and drug-uremic toxin interactions in the liver.
AB  - PURPOSE: Organic anion-transporting polypeptide (OATP) 1B1 and OATP1B3 contribute
      to hepatic uptake of numerous drugs. Thus, reduced OATP1B1 and OATP1B3 activity
      in chronic kidney disease (CKD) may have a major impact on the hepatic clearance
      of drugs. The effect of drug-uremic toxin interactions on OATP1B1 and OATP1B3 has
      not been well studied. In the present study, we examine the inhibitory effects of
      uremic toxins on OATP1B1 and OATP1B3 transport activity to evaluate the
      interactions between drugs and uremic toxins in patients with chronic kidney
      disease. METHODS. [3H]Estron-3-sulfate, [3H]taurocholate uptake and
      [3H]methotrexate by OATP1B1 and OATP1B3 expressing HEK293 cells were performed to
      evaluate the inhibitory effect of uremic toxins. To clarify whether the uremic
      toxins that interact with OATP1B1 and/or OATP1B3 were substrates for these
      transporters, we performed uptake studies. RESULTS. Four uremic toxins, kynurenic
      acid, indole-3-acetic acid, indoxyl sulfate, and p-cresol, inhibited OATP1B1- and
      OATP1B3-mediated transport in a concentration-dependent manner, with IC50 values
      of 180, 770, 2700, and 4600 uM, respectively, for OATP1B1 and 180, 1100, 1300,
      and 1700 uM, respectively, for OATP1B3. [3H]Methotrexate uptake by OATPs was also
      inhibited by the four uremic toxins in a dose-dependent manner. Uptake studies
      revealed that kynurenic acid is a substrate for both the OATP1B1 and OATP1B3.
      Moreover, OATP1B3 was involved in the transport of indoxyl sulfate. Indole-3
      acetic acid and p-cresol were not significantly transported by OATP1B1 and
      OATP1B3. CONCLUSIONS. We showed that some uremic toxins inhibit OATP-mediated
      uptake in a concentration-dependent manner, and clarified OATPs contribution to
      uremic toxin handling in the liver. Thus, we provided basic information to
      estimate the inhibitory effects of uremic toxins on OATPs in CKD patients. These
      data suggest that the dose of drugs excreted via renal and non-renal pathways
      should be carefully adjusted in CKD patients.

PMID- 25579431
TI  - Risk of infections of biological therapies with accent on inflammatory bowel
      disease.
AB  - BACKGROUND: Biological therapies using anti-tumor necrosis factor (TNF)-alpha
      agents have an important impact in the treatment of inflammatory bowel disease,
      rheumatoid arthritis, psoriasis, and other inflammatory conditions. However, a
      significant number of patients lose their response to these medications over
      time. Clinical trials have demonstrated that antibodies against anti-TNF agents
      may impact treatment response and increase the risk of infusion reactions. Of
      concern is also the possibility of developing adverse events induced by anti-TNF
      agents. The purpose of the present systematic review is to describe the current
      knowledge on the risk of infections associated with anti-TNF agents antagonists,
      as well as integrin antagonists. We also intend to describe case reports of these
      adverse events in inflammatory bowel disease patients. METHODS: Currently
      approved anti-TNF biologicals in IBD include the monoclonal antibodies
      infliximab, adalimumab, certolizumab pegol and golimumab. Integrin antagonists
      include natalizumab, etrolizumab and vedolizumab. RESULTS: The most frequently
      reported adverse events of these biologicals were infections, and these are
      described in detail in this study. DISCUSSION: Most adverse events are due to the
      failure of host immunological control, which involves de novo infection, or
      reactivation of latent bacterial or viral infection, often with a different
      expression of disease. CONCLUSION: Risk assessment in individuals undergoing
      treatment with biologicals represents a step towards achieving treatment
      personalization to identify those patients that will safely benefit from this
      therapeutic approach. Patients and physicians must be alert for anti-TNF agents
      and anti-integrin medication as potential causes of drug-induced infections and
      monitor the therapies. Personalizing therapeutic vigilance promises to optimize
      benefits while minimizing infections.

PMID- 25579432
TI  - To be drug or prodrug: structure-property exploratory approach regarding oral
      bioavailability.
AB  - PURPOSE: Prodrug design is a strategy that can be used to adjust physicochemical
      properties of drugs in order to overcome pharmacokinetic problems, such as poor
      oral bioavailability. However, Lipinski's and Veber's rules predict whether
      compounds will have absorption problems even before the design of prodrugs. In
      this context, our goal was to evaluate the molecular properties which most
      influenced the absorption process of prodrugs compared to its precursor through
      exploratory data analysis approach. METHODS: A variety of prodrugs and respective
      precursors were randomly selected and classified by its percentage of human
      intestinal absorption. Subsequently, different molecular properties were
      calculated and hierarchical cluster analysis (HCA) and principal components
      analysis (PCA) were carried out. RESULTS: According to the findings, antiviral,
      anti-hypertensive, and antibiotic prodrugs exhibited higher absorption levels
      than their respective precursors. Also, some relevant descriptors (molecular
      weight, MW, routable bonds, rot_bonds, hydrogen bond acceptors, HBA_count and
      polar surface area, PSA), which are included in Lipinski's and Veber's rules,
      influenced the separation process between prodrugs and drugs. Furthermore, other
      molecular properties, such as polarizability (alpha) and molar refractivity (MR),
      were pointed out. CONCLUSION: Lipinski's and Veber's rules proved to be important
      to design an orally administered drug but other descriptors should be considered
      by medicinal chemists in the prodrug designing process.

PMID- 25579433
TI  - Co-encapsulated CpG oligodeoxynucleotides and ovalbumin in PLGA microparticles;
      an in vitro and in vivo study.
AB  - PURPOSE: The objective of this work was to evaluate the effect in the immune
      response produced by CpG oligodeoxynucleotides (ODN) co-encapsulated with the
      antigen ovalbumin (OVA) within poly(lactic-co-glycolic) acid (PLGA) 502 and 752
      microparticles (MP). METHODS: MP were prepared by blending 1,2-dioleoyl-3
      trimethylammonium-propane (DOTAP) with PLGA and Total Recirculation One Machine
      System (TROMS) technology and contained OVA along with CpG sequences associated
      to DOTAP. After confirming the integrity of both encapsulated molecules, BALB/c
      mice were immunized with the resulting MP and OVA-specific antibodies and
      cytokine production were assessed in order to determine the immunological profile
      induced in mice. RESULTS: One ?m near non-charged MP co-encapsulated very
      efficiently both OVA and CpG ODN. The release of both OVA and CpG was slow and
      incomplete irrespective of polymer. The results of the immune response induced in
      BALB/c mice indicated that, depending on the PLGA polymer used, co-encapsulation
      did not improve the immunogenicity of the antigen, compared either with the
      simply co-administration of both antigen and CpG, or with the microencapsulated
      antigen. Thus, mice immunized with OVA associated to PLGA 756 displayed an IgG2a
      characterized response which was biased to an IgG1 profile in case of CpG co
      encapsulation. On the contrary, the co-encapsulation of CpG with OVA into PLGA
      502 significantly improved the isotype shifting in comparison with the one showed
      by mice immunized with OVA loaded PLGA 502. CONCLUSION: This study underlines the
      importance of MP characteristics to fully exploit simultaneous antigen and CpG
      ODN particulate delivery as effective vaccine construct.This article is open to
      POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by
      clicking on ABSTRACT on the issue's contents page.

PMID- 25579434
TI  - Influence of ascorbic acid supplementation on type 2 diabetes mellitus in
      observational and randomized controlled trials; a systematic review with meta
      analysis.
AB  - PURPOSE: There are controversial data regarding the beneficial effects of
      ascorbic acid (AA) supplementation in type 2 diabetes mellitus (T2DM). In this
      systematic review, we aimed to criticize the current relevant data from both
      observational and randomized controlled trials (RCTs). METHODS: All observational
      and RCTs conducted to assess anti-hyperglycemic effects of AA in diabetics,
      published before January 2013, were included. To obtain all related studies
      Google Scholar, PubMed, Scopus, IranMedex, and Magiran web databases were
      searched. Exclusion criteria were animal studies, and studies conducted in Type 1
      DM, children or pregnant women. Main outcome measures were fasting blood sugar
      (FBS), and glycated hemoglobin (HbA1c). According to degree of heterogeneity,
      fixed or random effect models were employed. Meta-analyses were done using Stats
      Direct software, version 3.0.97. The quality of included articles and publication
      bias were also assessed. RESULTS: We selected 38 articles; 26 observational
      studies and 12 RCTs. Due to severe methodological heterogeneity in all
      observational studies and some of RCTs, we could pool data from only 5 RCTs in a
      meta-analysis. Single intake of AA versus placebo showed a significant effect on
      FBS; with the standardized mean difference (SMD): -20.59, 95% confidence
      intervals (95% CI): -40.77 to -0.4 (p= 0.04), but non-significant effect on
      HbA1c; SMD: -0.46, 95% CI: -1.75 to 0.84 (p= 0.4). Effect of other antioxidants
      with/without AA supplementation on FBSwere nonsignificant; SMD: -4.26 (p= 0.8),
      and SMD: -12.04 (p= 0.3), respectively. Also, their effect on HbA1c was non
      significant; SMD: 0.53 (p= 0.11), and SMD: 0.28 (p= 0.34), respectively.
      CONCLUSIONS: Our study supports the positive effect of AA in reduction of FBS in
      diabetics, however, due to insufficient evidence ragarding long term safety of AA
      supplementation and limited number of RCTs, the long term use of this vitamin for
      its anti-diabetic properties cannot be strongly recommended.

PMID- 25579435
TI  - Iron complexation to histone deacetylase inhibitors SAHA and LAQ824 in PEGylated
      liposomes can considerably improve pharmacokinetics in rats.
AB  - PURPOSE: The formulation of histone deacetylase inhibitors (HDACi) is challenging
      due to poor water solubility and rapid elimination of drugs in vivo. This study
      investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide
      hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into
      PEGylated liposomes, and investigated whether this technique could improve drug
      solubility, in vitro release and in vivo pharmacokinetic (PK) properties.
      METHODS. The reaction stoichiometry, binding constants and solubility were
      measured for Fe complexes of SAHA and LAQ. The complexes were passively
      encapsulated into PEGylated liposomes and characterized by size distribution,
      zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies.
      PC-3 cells were used to verify the in vitro anticancer activity of the
      formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe)
      was evaluated in rats. RESULTS. SAHA and LAQ form complexes with Fe at 1:1
      stoichiometric ratio, with a binding constant on the order of 104 M-1. Fe
      complexation improved the aqueous solubility and the liposomal encapsulation
      efficiency of SAHA and LAQ (29-35% EE, final drug concentration > 1 mM).
      Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro
      release properties compared to L-HDACi but cytotoxicity on PC-3 cells was
      comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the
      plasma t1/2 (12.11 h)and 211-fold improvement in the AUCinfinity (105.7 ug.h/ml)
      compared to free LAQ (0.79 h, 0.5 ug.h/ml). Similarly, the plasma t1/2 of Fe was
      determined to be 11.83 h in a separate experiment using radioactive Fe-59. The
      majority of Fe-59 activity was found in liver and spleen of rats and correlates
      with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS. We have
      demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes
      can improve overall drug aqueous solubility, in vitro release and in vivo
      pharmacokinetic properties.

PMID- 25579436
TI  - Predictive modelling of survival and length of stay in critically ill patients
      using sequential organ failure scores.
AB  - INTRODUCTION: The length of stay of critically ill patients in the intensive care
      unit (ICU) is an indication of patient ICU resource usage and varies
      considerably. Planning of postoperative ICU admissions is important as ICUs often
      have no nonoccupied beds available. PROBLEM STATEMENT: Estimation of the ICU bed
      availability for the next coming days is entirely based on clinical judgement by
      intensivists and therefore too inaccurate. For this reason, predictive models
      have much potential for improving planning for ICU patient admission. OBJECTIVE:
      Our goal is to develop and optimize models for patient survival and ICU length of
      stay (LOS) based on monitored ICU patient data. Furthermore, these models are
      compared on their use of sequential organ failure (SOFA) scores as well as
      underlying raw data as input features. METHODOLOGY: Different machine learning
      techniques are trained, using a 14,480 patient dataset, both on SOFA scores as
      well as their underlying raw data values from the first five days after
      admission, in order to predict (i) the patient LOS, and (ii) the patient
      mortality. Furthermore, to help physicians in assessing the prediction
      credibility, a probabilistic model is tailored to the output of our best
      performing model, assigning a belief to each patient status prediction. A two-by
      two grid is built, using the classification outputs of the mortality and
      prolonged stay predictors to improve the patient LOS regression models. RESULTS:
      For predicting patient mortality and a prolonged stay, the best performing model
      is a support vector machine (SVM) with GA,D=65.9% (area under the curve (AUC) of
      0.77) and GS,L=73.2% (AUC of 0.82). In terms of LOS regression, the best
      performing model is support vector regression, achieving a mean absolute error of
      1.79 days and a median absolute error of 1.22 days for those patients surviving a
      nonprolonged stay. CONCLUSION: Using a classification grid based on the predicted
      patient mortality and prolonged stay, allows more accurate modeling of the
      patient LOS. The detailed models allow to support the decisions made by
      physicians in an ICU setting.

PMID- 25579437
TI  - Different forms of apolipophorin III in Galleria mellonella larvae challenged
      with bacteria and fungi.
AB  - Apolipophorin III (apoLp-III), a lipid-binding protein and an insect homolog of
      human apolipoprotein E, plays an important role in lipid transport and immune
      response in insects. In the present study, we have demonstrated a correlation in
      time between changes in the apoLp-III abundance occurring in the hemolymph,
      hemocytes, and fat body after immunization of Galleria mellonella larvae with
      Gram-negative bacteria Escherichia coli, Gram-positive bacteria Micrococcus
      luteus, yeast Candida albicans, and a filamentous fungus Fusarium oxysporum.
      Using two-dimensional electrophoresis (IEF/SDS-PAGE) and immunoblotting with anti
      apoLp-III antibodies, the profile of apoLp-III forms in G. mellonella larvae
      challenged with the bacteria and fungi has been analyzed. Besides the major apoLp
      III protein (pI=6.5), one and three additional apoLp-III forms differing in the
      pI value have been detected, respectively, in the hemolymph, hemocytes, and fat
      body of non-immunized insects. Also, evidence has been provided that particular
      apoLp-III-derived polypeptides appear after the immune challenge and are present
      mainly in the hemolymph and hemocytes. The time of their appearance and
      persistence in the hemolymph was dependent on the pathogen used. At least two of
      the apoLp-III forms detected in hemolymph bound to the microbial cell surface.
      The increasing number of hemolymph apoLp-III polypeptides and differences in
      their profiles observed in time after the challenge with different immunogens
      confirmed the important role of apoLp-III in discriminating between pathogens by
      the insect defense system and in antibacterial as well as antifungal immune
      response. 

PMID- 25579438
TI  - Gene Targeting Through Homologous Recombination in Monkey Embryonic Stem Cells
      Using CRISPR/Cas9 System.

PMID- 25579446
TI  - Upright face-preferential high-gamma responses in lower-order visual areas:
      evidence from intracranial recordings in children.
AB  - Behavioral studies demonstrate that a face presented in the upright orientation
      attracts attention more rapidly than an inverted face. Saccades toward an upright
      face take place in 100-140 ms following presentation. The present study using
      electrocorticography determined whether upright face-preferential neural
      activation, as reflected by augmentation of high-gamma activity at 80-150 Hz,
      involved the lower-order visual cortex within the first 100 ms post-stimulus
      presentation. Sampled lower-order visual areas were verified by the induction of
      phosphenes upon electrical stimulation. These areas resided in the lateral
      occipital, lingual, and cuneus gyri along the calcarine sulcus, roughly
      corresponding to V1 and V2. Measurement of high-gamma augmentation during central
      (circular) and peripheral (annular) checkerboard reversal pattern stimulation
      indicated that central-field stimuli were processed by the more polar surface
      whereas peripheral-field stimuli by the more anterior medial surface. Upright
      face stimuli, compared to inverted ones, elicited up to 23% larger augmentation
      of high-gamma activity in the lower-order visual regions at 40-90 ms. Upright
      face-preferential high-gamma augmentation was more highly correlated with high
      gamma augmentation for central than peripheral stimuli. Our observations are
      consistent with the hypothesis that lower-order visual regions, especially those
      for the central field, are involved in visual cues for rapid detection of upright
      face stimuli.

PMID- 25579447
TI  - Neural activity associated with self, other, and object-based counterfactual
      thinking.
AB  - Previous research has shown that autobiographical episodic counterfactual
      thinking-i.e., mental simulations about alternative ways in which one's life
      experiences could have occurred-engages the brain's default network (DN).
      However, it remains unknown whether or not the DN is also engaged during
      impersonal counterfactual thoughts, specifically those involving other people or
      objects. The current study compares brain activity during counterfactual
      simulations involving the self, others and objects. In addition, counterfactual
      thoughts involving others were manipulated in terms of similarity and familiarity
      with the simulated characters. The results indicate greater involvement of DN
      during person-based (i.e., self and other) as opposed to object-based
      counterfactual simulations. However, the involvement of different regions of the
      DN during other-based counterfactual simulations was modulated by how close
      and/or similar the simulated character was perceived to be by the participant.
      Simulations involving unfamiliar characters preferentially recruited dorsomedial
      prefrontal cortex. Simulations involving unfamiliar similar characters,
      characters with whom participants identified personality traits, recruited
      lateral temporal gyrus. Finally, our results also revealed differential coupling
      of right hippocampus with lateral prefrontal and temporal cortex during
      counterfactual simulations involving familiar similar others, but with left
      transverse temporal gyrus and medial frontal and inferior temporal gyri during
      counterfactual simulations involving either oneself or unfamiliar dissimilar
      others. These results suggest that different brain mechanisms are involved in the
      simulation of personal and impersonal counterfactual thoughts, and that the
      extent to which regions associated with autobiographical memory are recruited
      during the simulation of counterfactuals involving others depends on the
      perceived similarity and familiarity with the simulated individuals. 

PMID- 25579449
TI  - Maximally reliable spatial filtering of steady state visual evoked potentials.
AB  - Due to their high signal-to-noise ratio (SNR) and robustness to artifacts, steady
      state visual evoked potentials (SSVEPs) are a popular technique for studying
      neural processing in the human visual system. SSVEPs are conventionally analyzed
      at individual electrodes or linear combinations of electrodes which maximize some
      variant of the SNR. Here we exploit the fundamental assumption of evoked
      responses--reproducibility across trials--to develop a technique that extracts a
      small number of high SNR, maximally reliable SSVEP components. This novel spatial
      filtering method operates on an array of Fourier coefficients and projects the
      data into a low-dimensional space in which the trial-to-trial spectral covariance
      is maximized. When applied to two sample data sets, the resulting technique
      recovers physiologically plausible components (i.e., the recovered topographies
      match the lead fields of the underlying sources) while drastically reducing the
      dimensionality of the data (i.e., more than 90% of the trial-to-trial reliability
      is captured in the first four components). Moreover, the proposed technique
      achieves a higher SNR than that of the single-best electrode or the Principal
      Components. We provide a freely-available MATLAB implementation of the proposed
      technique, herein termed "Reliable Components Analysis".

PMID- 25579450
TI  - Dynamics of a caged imidazolium cation-toward understanding the order-disorder
      phase transition and the switchable dielectric constant.
AB  - A molecular compass-like behaviour is found in a perovskite-type cage compound
      (HIm)2[KCo(CN)6] (HIm = imidazolium cation). The dynamic changes in the HIm
      cation from the static to rotating state along with the rearrangement of the host
      cage result in switchable and anisotropic dielectric constants. 

PMID- 25579448
TI  - Functional MRI mapping of dynamic visual features during natural viewing in the
      macaque.
AB  - The ventral visual pathway of the primate brain is specialized to respond to
      stimuli in certain categories, such as the well-studied face selective patches in
      the macaque inferotemporal cortex. To what extent does response selectivity
      determined using brief presentations of isolated stimuli predict activity during
      the free viewing of a natural, dynamic scene, where features are superimposed in
      space and time? To approach this question, we obtained fMRI activity from the
      brains of three macaques viewing extended video clips containing a range of
      social and nonsocial content and compared the fMRI time courses to a family of
      feature models derived from the movie content. Starting with more than two dozen
      feature models extracted from each movie, we created functional maps based on
      features whose time courses were nearly orthogonal, focusing primarily on faces,
      motion content, and contrast level. Activity mapping using the face feature model
      readily yielded functional regions closely resembling face patches obtained using
      a block design in the same animals. Overall, the motion feature model dominated
      responses in nearly all visually driven areas, including the face patches as well
      as ventral visual areas V4, TEO, and TE. Control experiments presenting dynamic
      movies, whose content was free of animals, demonstrated that biological movement
      critically contributed to the predominance of motion in fMRI responses. These
      results highlight the value of natural viewing paradigms for studying the brain's
      functional organization and also underscore the paramount contribution of
      magnocellular input to the ventral visual pathway during natural vision. 

PMID- 25579451
TI  - Improving and repurposing biocatalysts via directed evolution.
AB  - Over the last two decades, directed evolution has become a staple in protein
      engineering and ushered in a new era of industrial biocatalysis. Directed
      evolution has provided the tools to not only improve the activity of known
      biocatalysts, but also to endow biocatalysts with chemical reactivities not
      previously encountered in nature. Here we will discuss the recent successes in
      the quest to enhance thermostability, stereoselectivity and activity of
      biocatalysts, as well as to create novel enzymes, over the last two years. 

PMID- 25579452
TI  - Artificial metalloenzymes derived from three-helix bundles.
AB  - Three-helix bundles and coiled-coil motifs are well-established de novo designed
      scaffolds that have been investigated for their metal-binding and catalytic
      properties. Satisfaction of the primary coordination sphere for a given metal is
      sufficient to introduce catalytic activity and a given structure may catalyze
      different reactions dependent on the identity of the incorporated metal. Here we
      describe recent contributions in the de novo design of metalloenzymes based on
      three-helix bundles and coiled-coil motifs, focusing on non-heme systems for
      hydrolytic and redox chemistry. 

PMID- 25579454
TI  - DNA-based hybrid catalysis.
AB  - In the past decade, DNA-based hybrid catalysis has merged as a promising novel
      approach to homogeneous (asymmetric) catalysis. A DNA hybrid catalysts comprises
      a transition metal complex that is covalently or supramolecularly bound to DNA.
      The chiral microenvironment and the second coordination sphere interactions
      provided by the DNA are key to achieve high enantioselectivities and, often,
      additional rate accelerations in catalysis. Nowadays, current efforts are focused
      on improved designs, understanding the origin of the enantioselectivity and DNA
      induced rate accelerations, expanding the catalytic scope of the concept and
      further increasing the practicality of the method for applications in synthesis.
      Herein, the recent developments will be reviewed and the perspectives for the
      emerging field of DNA-based hybrid catalysis will be discussed. 

PMID- 25579453
TI  - Using non-enzymatic chemistry to influence microbial metabolism.
AB  - The structural manipulation of small molecule metabolites occurs in all organisms
      and plays a fundamental role in essentially all biological processes. Despite an
      increasing interest in developing new, non-enzymatic chemical reactions capable
      of functioning in the presence of living organisms, the ability of such
      transformations to interface with cellular metabolism and influence biological
      function is a comparatively underexplored area of research. This review will
      discuss efforts to combine non-enzymatic chemistry with microbial metabolism. We
      will highlight recent and historical uses of non-biological reactions to study
      microbial growth and function, the use of non-enzymatic transformations to rescue
      auxotrophic microorganisms, and the combination of engineered microbial
      metabolism and biocompatible chemical reactions for organic synthesis. 

PMID- 25579455
TI  - Use of the confined spaces of apo-ferritin and virus capsids as nanoreactors for
      catalytic reactions.
AB  - Self-assembled protein cages providing nanosized internal spaces which are
      capable of encapsulating metal ions/complexes, enzymes/proteins have great
      potential for use as catalytic nanoreactors in efforts to mimic confined cellular
      environments for synthetic applications. Despite many uses in biomineralization,
      drug delivery, bio-imaging and so on, applications in catalysis are relatively
      rare. Because of their restricted size, protein cages are excellent candidates
      for use as vessels to exert control over reaction kinetics and product
      selectivity. Virus capsids with larger internal spaces can encapsulate multiple
      enzymes and can mimic natural enzymatic reactions. The apo-ferritin cage is known
      to accommodate various metal ions/complexes and suitable for organic
      transformation reactions in an aqueous medium. This review highlights the
      importance, prospects and recent significant research on catalytic reactions
      using the apo-ferritin cage and virus capsids. 

PMID- 25579457
TI  - New activation cross section data on longer lived radio-nuclei produced in proton
      induced nuclear reaction on zirconium.
AB  - The excitation functions of (96)Nb, (95m)Nb, (95g)Nb, (92m)Nb, (91m)Nb, (90)Nb,
      (95)Zr, (89)Zr, (88)Zr, (86)Zr, (88)Y, (87m)Y, (87g)Y, (86)Y were measured up to
      70MeV proton energy by using the stacked foil technique and the activation
      method. The new data were compared with the critically analyzed experimental data
      in the literature and with the TALYS based model results in TENDL-2013 library.
      The possible role of the investigated reactions in the production of medically
      relevant (90)Nb, (95m)Nb, (89)Zr, and (88)Y radionuclides is discussed. 

PMID- 25579458
TI  - Primary standardization of SIR-Spheres based on the dissolution of the (90)Y
      labeled resin microspheres.
AB  - The project "Metrology for molecular radiotherapy" is a collaborative European
      project initiated to bring together expertize in ionizing radiation metrology and
      nuclear medicine research. This project deals with the development of
      personalized dosimetry to individual patients who are undergoing molecular
      radiotherapy (also known as targeted radionuclide therapy). The general aim is to
      provide a metrological traceability to primary standards for individual dosimetry
      in the case of molecular radiotherapy. In particular, one objective is the
      standardization of (90)Y-labeled resin microspheres SIR-Spheres (Sirtex, Sydney,
      Australia) used for the treatment of liver cancer by radioembolization. The
      present paper describes the primary measurements carried out using the Triple to
      Double Coincidence Ratio (TDCR) method applied after the complete dissolution of
      the SIR-Spheres in the Sirtex vial. A method for the dissolution was developed to
      optimize the homogeneity of the solution to enable the primary measurements based
      on Cherenkov and liquid scintillation counting. A comprehensive description of
      the protocol implemented for the microsphere dissolution is reported. First
      calibration factors obtained with the reference ionization chambers at LNE-LNHB
      are also given. 

PMID- 25579456
TI  - Changes in [18F]Fluoro-2-deoxy-D-glucose incorporation induced by doxorubicin and
      anti-HER antibodies by breast cancer cells modulated by co-treatment with
      metformin and its effects on intracellular signalling.
AB  - PURPOSES: Metformin, currently undergoing clinical trials as an adjuvant for the
      treatment of breast cancer, modulates the activity of key intracellular
      signalling molecules which affect 2-[(18)F]Fluoro-2-deoxy-D-glucose ([(18)F]FDG)
      incorporation. Here, we investigate the effect of drugs used in the treatment of
      breast cancer combined with metformin on [(18)F]FDG incorporation in HER2- or
      HER1-overexpressing breast cancer cells to determine whether or not metformin may
      obscure changes in [(18)F]FDG incorporation induced by clinically utilised
      anticancer drugs in the treatment of breast cancer. METHODS: Three breast cancer
      cell lines expressing HER2 and one HER2 negative but HER1 positive were exposed
      to metformin, doxorubicin and trastuzumab or cetuximab. Cytotoxicity was measured
      by the MTT assay. Expression of active (phospho-) AMPK, PKB (Akt) and ERK was
      determined by Western blotting. [(18)F]FDG incorporation by cells exposed to drug
      combinations with metformin was determined. Glucose transport was assessed by
      measuring the initial rate of uptake of [(3)H]O-methyl-D-glucose ([(3)H]OMG).
      Phosphorylation of [(18)F]FDG was determined in intact cells after exposure to
      [(18)F]FDG. RESULTS: Phospho-AMPK was increased by metformin in all cell lines
      whilst phospho-Akt and phospho-ERK expressions were decreased in two. Metformin
      treatment increased [(18)F]FDG incorporation in all cell lines, and treatment
      with anti-HER antibodies or doxorubicin only produced minor modulations in the
      increase induced by metformin alone. Glucose transport was increased in BT474
      cells and decreased in SKBr3 and MDA-MB-468 cells after treatment with metformin.
      The fraction of phosphorylated [(18)F]FDG was increased in metformin-treated
      cells compared with controls, suggesting that hexokinase efficiency was increased
      by metformin. CONCLUSION: This is the first study to show that increased
      [(18)F]FDG incorporation by breast cancer cells induced by metformin overwhelms
      the effect of doxorubicin and anti-HER treatments on [(18)F]FDG incorporation.
      Metformin-induced increased [(18)F]FDG incorporation was consistently associated
      with enhanced [(18)F]FDG phosphorylation.

PMID- 25579459
TI  - Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With
      Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth
      Factor Receptor 2-Positive Operable Breast Cancer.
AB  - We treated patients with operable human epidermal growth factor receptor 2
      positive breast cancer with neoadjuvant anthracycline regimens followed by
      nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49%
      achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in
      the patients with estrogen receptor-positive and -negative cancer, respectively.
      Neoadjuvant therapy using this combination appears to be effective and safe.
      Introduction: Neoadjuvant chemotherapy plus trastuzumab. INTRODUCTION:
      Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic
      complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)
      positive breast cancer and has been associated with improved therapeutic
      outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this
      patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce
      the toxicity of PTX while maintaining its efficacy. The present study evaluated
      the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast
      cancer. PATIENTS AND METHODS: We treated patients with stage I to IIIA breast
      cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5
      fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles,
      followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary
      endpoint was the pCR rate. The secondary endpoints included the clinical response
      rate, disease-free survival, pathologic response rate (defined as pCR or minimal
      residual invasive disease only in the breast), breast-conserving surgery rate,
      and safety. RESULTS: Forty-six patients were enrolled. One patient met the
      exclusion criteria because of the coexistence of another malignant disease;
      therefore, we evaluated 45 patients in the entire study. One patient experienced
      rapid disease progression during EC therapy, leaving 44 patients evaluable for
      nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36%
      and 71% in those with estrogen receptor-positive and -negative cancer,
      respectively. Of all the study treatments, the most frequent reason for delay or
      dose reduction was hematologic toxicity; only 1 patient required a dose reduction
      for nab-PTX because of peripheral neuropathy. CONCLUSION: Neoadjuvant therapy
      using this combination appears to be effective and safe.

PMID- 25579460
TI  - Magnetic resonance imaging-guided core needle breast biopsies resulting in high
      risk histopathologic findings: upstage frequency and lesion characteristics.
AB  - Analysis of magnetic resonance imaging-guided breast biopsies yielding high-risk
      histopathologic features at a single institution found an overall upstage rate to
      malignancy of 14% at surgical excision. All upstaged lesions were associated with
      atypical ductal hyperplasia. Flat epithelial atypia and atypical lobular
      hyperplasia alone or with lobular carcinoma in situ were not associated with an
      upstage to malignancy. INTRODUCTION: The purpose of the present study w as to
      determine the malignancy upstage rates and imaging features of high-risk
      histopathologic findings resulting from magnetic resonance imaging (MRI)-guided
      core needle breast biopsies. These features include atypical ductal hyperplasia
      (ADH), atypical lobular hyperplasia (ALH), flat epithelial atypia (FEA), and
      lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: A retrospective medical
      record review was performed on all MRI-guided core needle breast biopsies at a
      single institution from June 1, 2007 to December 1, 2013 to select biopsies
      yielding high-risk histopathologic findings. The patient demographics, MRI lesion
      characteristics, and histopathologic features at biopsy and surgical excision
      were analyzed. RESULTS: A total of 257 MRI-guided biopsies had been performed,
      and 50 yielded high-risk histopathologic features (19%). Biopsy site and surgical
      excision site correlation was confirmed in 29 of 50 cases. Four of 29 lesions
      (14%) were upstaged: 1 case to invasive ductal carcinoma and 3 cases to ductal
      carcinoma in situ. ADH alone had an overall upstage rate of 7% (1 of 14), mixed
      ADH/ALH a rate of 75% (3 of 4), ALH alone or with LCIS a rate of 0% (0 of 7), and
      FEA a rate of 0% (0 of 4). Only mixed ADH/ALH had a statistically significant
      upstage rate to malignancy compared with the other high-risk histopathologic
      subtypes combined. No specific imaging characteristics on MRI were associated
      with an upstage to malignancy on the statistical analysis. CONCLUSION: MRI-guided
      breast biopsies yielding high-risk histopathologic features were associated with
      an overall upstage to malignancy rate of 14% at surgical excision. All upstaged
      lesions were associated with ADH. FEA and ALH alone or with LCIS were not
      associated with an upstage to malignancy.

PMID- 25579461
TI  - Isothermal circular-strand-displacement polymerization of DNA and microRNA in
      digital microfluidic devices.
AB  - Nucleic-acid amplification is a crucial step in nucleic-acid-sequence-detection
      assays. The use of digital microfluidic devices to miniaturize amplification
      techniques reduces the required sample volume and the analysis time and offers
      new possibilities for process automation and integration in a single device. The
      recently introduced droplet polymerase-chain-reaction (PCR) amplification methods
      require repeated cycles of two or three temperature-dependent steps during the
      amplification of the nucleic-acid target sequence. In contrast, low-temperature
      isothermal-amplification methods have no need for thermal cycling, thus requiring
      simplified microfluidic-device features. Here, the combined use of digital
      microfluidics and molecular-beacon (MB)-assisted isothermal circular-strand
      displacement polymerization (ICSDP) to detect microRNA-210 sequences is
      described. MicroRNA-210 has been described as the most consistently and
      predominantly upregulated hypoxia-inducible factor. The nmol L(-1)-pmol L(-1)
      detection capabilities of the method were first tested by targeting single
      stranded DNA sequences from the genetically modified Roundup Ready soybean. The
      ability of the droplet-ICSDP method to discriminate between full-matched, single
      mismatched, and unrelated sequences was also investigated. The detection of a
      range of nmol L(-1)-pmol L(-1) microRNA-210 solutions compartmentalized in
      nanoliter-sized droplets was performed, establishing the ability of the method to
      detect as little as 10(-18) mol of microRNA target sequences compartmentalized in
      20 nL droplets. The suitability of the method for biological samples was tested
      by detecting microRNA-210 from transfected K562 cells.

PMID- 25579462
TI  - Combining capillary electrophoresis and next-generation sequencing for aptamer
      selection.
AB  - Next-generation sequencing (NGS) machines can sequence millions of DNA strands in
      a single run, such as oligonucleotide (oligo) libraries comprising millions to
      trillions of discrete oligo sequences. Capillary electrophoresis is an attractive
      technique to select tight binding oligos or "aptamers" because it requires
      minimal sample volumes (e.g., 100 nL) and offers a solution-phase selection
      environment through which enrichment of target-binding oligos can be determined
      quantitatively. We describe here experiments using capillary transient
      isotachophoresis (ctITP)-based nonequilibrium capillary electrophoresis of
      equilibrium mixtures (NECEEM) as a method for selecting aptamers from a
      randomized library containing a known (29mer) thrombin-binding aptamer. Our
      capillary electrophoresis (CE)-selected samples were sequenced by the Ion Torrent
      Personal Genome Machine (PGM) and analyzed for selection efficiency. We show that
      a single round of CE selection can enrich a randomer synthetic DNA oligo mixture
      for thrombin-binding activity from 0.4% aptamer content before selection to >15%
      aptamer content.

PMID- 25579463
TI  - Highly sensitive analysis of polyphenols and their metabolites in human blood
      cells using dispersive SPE extraction and LC-MS/MS.
AB  - Blood cells, particularly erythrocytes, present a significant compartment for
      distribution of drugs and endogenous compounds and have been suggested to be
      factored in pharmacokinetic and pharmacodynamic evaluations. We previously
      detected the binding of polyphenols to red blood cells and found indications for
      a facilitated uptake of the bioactive procyanidin metabolite delta-(3,4-dihydroxy
      phenyl)-gamma-valerolactone (M1) into human erythrocytes. The purpose of the
      present investigation was to develop an effective, sensitive and robust liquid
      chromatography tandem mass spectrometry (LC-MS/MS) method to quantify low
      concentrations of polyphenols in human blood cells. Various sample preparation
      methods including classic sample clean-up techniques and variations of the
      QuEChERS (quick, easy, cheap, effective, rugged and safe) approach were compared
      regarding compound recovery, matrix effects and overall process efficiency. The
      QuEChERS technique which involves a liquid-liquid extraction and clean-up by
      dispersive solid-phase extraction yielded best results. The method was fully
      validated for the six analytes: (+)-catechin, ferulic acid, M1, taxifolin,
      caffeic acid and delta-3-methoxy-4-hydroxy-phenyl- gamma-valerolactone (M2) in
      human blood cells with an optimised QuEChERS sample preparation and prior
      enzymatic hydrolysis of analyte conjugates. The lower limits of quantification
      for the analytes ranged from 0.12 ng/mL for M1, M2 and taxifolin to 48.40 ng/mL
      for caffeic acid. The application of the method to a blood cell sample of a
      volunteer ingesting 100 mg/day of the standardised pine bark extract
      Pycnogenol((r)) over the course of 3 weeks revealed measurable steady-state
      concentrations of catechin, M1, taxifolin, ferulic acid and M2. To our knowledge,
      this is the first report of using the QuEChERS approach for detection and
      quantification of plant-derived compounds in human blood cells. The method can be
      applied in pharmacokinetic studies to determine the distribution of polyphenols
      and their metabolites in human whole blood, blood cells or erythrocytes. This
      might contribute in gaining deeper insights into the in vivo distribution of
      polyphenols and their metabolites. 

PMID- 25579464
TI  - [An update on measles].
AB  - Measles is a highly contagious infectious disease, which needs more than 95%
      worldwide vaccination coverage of 2 doses to be eradicated. Despite an important
      involvement of the WHO for massive immunization, goals have not bean reached, and
      outbreaks can occur at any time in many countries, including Western Europe. In
      France, 22,000 cases were identified between 2009 and 2011, mainly in infants and
      young adults, which are not or not enough vaccinated (one dose). In 2012, even
      though the number of cases has drastically decreased, the outbreak is still going
      on, especially in South of France. That is why every clinician needs to be
      concerned about the clinical manifestations of the disease, and its
      complications. Besides a febrile rash, measles is often responsible of pneumonia
      and biologic hepatitis in adults. Hepatitis does not seem frequent in children.
      Clinicians need to be aware of specific complications, like encephalitis in case
      of cellular immunodepression, high risk of pneumonia in pregnant women. In
      patients previously vaccinated, incidence of complications is the same but
      patients are not contagious. Even if measles diagnosis is clinical, blood
      confirmation by serology is recommended in France when possible. Outcome is
      mainly favourable, but measles is not well-tolerated with high levels of
      hospitalisation even without any complication. Vaccination is the only way to
      protect against it.

PMID- 25579465
TI  - [Systemic lupus erythematosus and antiphospholipid syndrome: How to manage
      pregnancy?].
AB  - Pregnancy in systemic lupus erythematosus patients is a common situation that
      remains associated with higher maternal and fetal mortality/morbidity than in the
      general population. Complications include lupus flares, obstetrical complications
      (fetal loss, in utero growth retardation, prematurity) and neonatal lupus
      syndrome. The association with antiphospholipid antibodies or antiphospholipid
      syndrome increases the risk of obstetrical complications. Improving the care of
      these pregnancies depends upon a systematic pregnancy planning, ideally during a
      preconception counseling visit and a multidisciplinary approach
      (internist/rheumatologist, obstetrician and anesthetist). The absence of lupus
      activity, the use of appropriate medications during pregnancy adjusted to the
      patient's medical history and risk factors, and a regular monitoring are the best
      tools for a favorable outcome for these high-risk pregnancies. The aim of this
      review article is to perform an update on the medical care of pregnancy in
      systemic lupus erythematosus or antiphospholipid syndrome to reduce the risk of
      complications and to ensure the best maternal and fetal prognosis. 

PMID- 25579466
TI  - The effect of sleep restriction on laser evoked potentials, thermal sensory and
      pain thresholds and suprathreshold pain in healthy subjects.
AB  - OBJECTIVE: Sleep restriction seems to change our experience of pain and reduce
      laser evoked potential (LEP) amplitudes. However, although LEP-habituation
      abnormalities have been described in painful conditions with comorbid sleep
      impairment, no study has previously measured the effect of sleep restriction on
      LEP-habituation, pain thresholds, and suprathreshold pain. METHOD: Sixteen males
      and seventeen females (aged 18-31years) were randomly assigned to either two
      nights of delayed bedtime and four hours sleep (partial sleep deprivation) or
      nine hours sleep. The study subjects slept at home, and the sleep was measured
      with actigraphy both nights and polysomnography the last night. LEP, thermal
      thresholds and suprathreshold pain ratings were obtained the day before and the
      day after intervention. The investigator was blinded. ANOVA was used to evaluate
      the interaction between sleep restriction and day for each pain-related variable.
      RESULTS: LEP-amplitude decreased after sleep restriction (interaction p=0.02)
      compared to subjects randomized to nine hours sleep. LEP-habituation was similar
      in both groups. Thenar cold pain threshold decreased after sleep restriction
      (interaction p=0.009). Supra-threshold heat pain rating increased temporarily 10s
      after stimulus onset after sleep restriction (interaction p=0.01), while it did
      not change after nine hours sleep. CONCLUSION: Sleep restriction reduced the CNS
      response to pain, while some of the subjective pain measures indicated
      hyperalgesia. SIGNIFICANCE: Since LEP-amplitude is known to reflect both CNS-pain
      specific processing and cognitive attentive processing, our results suggest that
      hyperalgesia after sleep restriction might partly be caused by a reduction in
      cortical cognitive or perceptual mechanisms, rather than sensory amplification.

PMID- 25579467
TI  - Preparation and evaluation of nanoparticles loaded ophthalmic in situ gel.
AB  - CONTEXT: Conventional ophthalmic solutions often eliminate rapidly after
      administration and cannot provide and maintain an adequate concentration of drug
      in the pre-corneal area. OBJECTIVES: Above problem can be overcome by the use of
      in situ gel forming systems that are instilled as drops in to the eye and undergo
      a sol-gel transition in the cul-de-sac. METHODS: An ion sensitive polymer gellan
      gum was used as gelling agent which formed immediate gel and remained for
      extended time period. Nanoparticles of moxifloxacin, prepared by solvent
      evaporation, were separated by freeze drying. The rheological properties and in
      vitro drug release test of in situ gel loaded with nanoparticles were evaluated
      and compared with marketed preparation. In vitro release study demonstrated
      diffusion controlled release for moxifloxacin from formulations over a period of
      12 h. RESULTS: The developed formulation was stable and showed enhanced contact
      time minimizing the frequency of administration. Confocal microscopy showed clear
      permeation of drug loaded nanoparticles across L/S of cornea. CONCLUSION: The
      formulation of moxifloxacin was found liquid at the formulated pH and formed gel
      in the presence of mono or divalent cations. The gel formed in situ showed
      sustained drug release over a period of 10-12 h. The formulations were less
      viscous before instillation and formed strong gel after instilling it into cul-de
      sac. It is thus concluded that by adopting a systematic formulation approach, an
      optimum point can be reached in the shortest time with minimum efforts to achieve
      desirable rheological and in vitro release property for in situ gel forming
      system.

PMID- 25579468
TI  - Hsp90 interaction with clients.
AB  - The conserved Hsp90 chaperone is an ATP-controlled machine that assists the
      folding and controls the stability of select proteins. Emerging data explain how
      Hsp90 achieves client specificity and its role in the cellular chaperone cascade.
      Interestingly, Hsp90 has an extended substrate binding interface that crosses
      domain boundaries, exhibiting specificity for proteins with hydrophobic residues
      spread over a large area regardless of whether they are disordered, partly
      folded, or even folded. This specificity principle ensures that clients
      preferentially bind to Hsp70 early on in the folding path, but downstream folding
      intermediates bind Hsp90. Discussed here, the emerging model is that the Hsp90
      ATPase does not modulate client affinity but instead controls substrate influx
      from Hsp70. 

PMID- 25579472
TI  - Endovascular challenges for complex lower extremity lesions?

PMID- 25579473
TI  - Bayesian model selection for multiple QTLs mapping combining linkage
      disequilibrium and linkage.
AB  - Linkage disequilibrium (LD) mapping is able to localize quantitative trait loci
      (QTL) within a rather small region (e.g. 2 cM), which is much narrower than
      linkage analysis (LA, usually 20 cM). The multilocus LD method utilizes haplotype
      information around putative mutation and takes historical recombination events
      into account, and thus provides a powerful method for further fine mapping.
      However, sometimes there are more than one QTLs in the region being studied. In
      this study, the Bayesian model selection implemented via the Markov chain Monte
      Carlo (MCMC) method is developed for fine mapping of multiple QTLs using
      haplotype information in a small region. The method combines LD as well as
      linkage information. A series of simulation experiments were conducted to
      investigate the behavior of the method. The results showed that this new multiple
      QTLs method was more efficient in separating closely linked QTLs than single
      marker association studies.

PMID- 25579471
TI  - Temporal delay discounting in acutely ill and weight-recovered patients with
      anorexia nervosa.
AB  - BACKGROUND: Patients with anorexia nervosa (AN) are characterized by a very low
      body weight but readily give up immediate rewards (food) for long-term goals
      (slim figure), which might indicate an unusual level of self-control. This
      everyday clinical observation may be quantifiable in the framework of the
      anticipation-discounting dilemma. METHOD: Using a cross-sectional design, this
      study compared the capacity to delay reward in 34 patients suffering from acute
      AN (acAN), 33 weight-recovered AN patients (recAN) and 54 healthy controls. We
      also used a longitudinal study to reassess 21 acAN patients after short-term
      weight restoration. A validated intertemporal choice task and a hyperbolic model
      were used to estimate temporal discounting rates. RESULTS: Confirming the
      validity of the task used, decreased delay discounting was associated with age
      and low self-reported impulsivity. However, no group differences in key measures
      of temporal discounting of monetary rewards were found. CONCLUSIONS: Increased
      cognitive control, which has been suggested as a key characteristic of AN, does
      not seem to extend the capacity to wait for delayed monetary rewards. Differences
      between our study and the only previous study reporting decreased delay
      discounting in adult AN patients may be explained by the different age range and
      chronicity of acute patients, but the fact that weight recovery was not
      associated with changes in discount rates suggests that discounting behavior is
      not a trait marker in AN. Future studies using paradigms with disorder-specific
      stimuli may help to clarify the role of delay discounting in AN.

PMID- 25579474
TI  - Standardized perfusion value of the esophageal carcinoma and its correlation with
      quantitative CT perfusion parameter values.
AB  - PURPOSE: Standardized perfusion value (SPV) is a universal indicator of tissue
      perfusion, normalized to the whole-body perfusion, which was proposed to
      simplify, unify and allow the interchangeability among the perfusion measurements
      and comparison between the tumor perfusion and metabolism. The aims of our study
      were to assess the standardized perfusion value (SPV) of the esophageal
      carcinoma, and its correlation with quantitative CT perfusion measurements: blood
      flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface
      area product (PS) of the same tumor volume samples, which were obtained by
      deconvolution-based CT perfusion analysis. METHODS: Forty CT perfusion studies of
      the esophageal cancer were analyzed, using the commercial deconvolution-based CT
      perfusion software (Perfusion 3.0, GE Healthcare). The SPV of the esophageal
      tumor and neighboring skeletal muscle were correlated with the corresponding mean
      tumor and muscle quantitative CT perfusion parameter values, using Spearman's
      rank correlation coefficient (rS). RESULTS: Median SPV of the esophageal
      carcinoma (7.1; range: 2.8-13.4) significantly differed from the SPV of the
      skeletal muscle (median: 1.0; range: 0.4-2.4), (Z=-5.511, p<0.001). The cut-off
      value of the SPV of 2.5 enabled discrimination of esophageal cancer from the
      skeletal muscle with sensitivity and specificity of 100%. SPV of the esophageal
      carcinoma significantly correlated with corresponding tumor BF (rS=0.484,
      p=0.002), BV (rS=0.637, p<0.001) and PS (rS=0.432, p=0.005), and SPV of the
      skeletal muscle significantly correlated with corresponding muscle BF (rS=0.573,
      p<0.001), BV (rS=0.849, p<0.001) and PS (rS=0.761, p<0.001). CONCLUSIONS: We
      presented a database of the SPV for the esophageal cancer and proved that SPV of
      the esophageal neoplasm significantly differs from the SPV of the skeletal
      muscle, which represented a sample of healthy tissue. The SPV was validated
      against quantitative CT perfusion measurements and statistically significant
      correlation was proved.

PMID- 25579475
TI  - Role of preoperative sonography in predicting conversion from laparoscopic
      cholecystectomy to open surgery.
AB  - BACKGROUND: Laparoscopic cholecystectomy is the first step treatment in
      cholelithiasis. The purpose of this study was to establish a radiologic view on
      prediction of conversion from laparoscopic cholecystectomy to open surgery.
      METHODS: This study included 176 patients who had undergone laparoscopic
      cholecystectomy. Preoperative ultrasonographic findings were assessed and we gave
      points to each finding according to results from correlation analysis. After the
      scoring we investigated the relationship between ultrasonographic findings and
      conversion from laparoscopic cholecystectomy to open surgery. RESULTS: Scoring
      significantly predicted failure in laparoscopic approach (AUC=0.758, P=0.003,).
      Optimal cut off score was found to be 1.95 with 67% sensitivity and 78%
      specificity. Score>1.95 was a risk factor for failure in laparoscopic approach
      [odds ratio=7.1(95% CI,2-24.9, P=0.002)]. There were 8 subjects out of 36(22%)
      with high score underwent open surgery while 4 out of 128 (3%) subjects with low
      score needed open surgery (p=0.002). Negative predictive value of 128/132=97%.
      Mean score of whole study population was 1.28 (range 0-8.8) and mean score of
      subjects underwent open surgery was 3.6 while it was 1.1 in successful
      laparoscopic approach group (p<0.001). Mean Age and BMI were similar between
      groups (p>0.05). Sex of subjects did not affect the success of surgery (p>0.05).
      CONCLUSION: The contribution of preoperative ultrasonography is emphasized in
      many studies. Our study suggests quantitative results on conversion from
      laparoscopic cholecystectomy to open surgery. We believe that radiologists have
      to indicate the risk of conversion in their ultrasonography reports.

PMID- 25579482
TI  - Postmenopausal hormone therapy and asthma-related hospital admission.

PMID- 25579483
TI  - Neonates with reduced neonatal lung function have systemic low-grade
      inflammation.
AB  - BACKGROUND: Children and adults with asthma and impaired lung function have been
      reported to have low-grade systemic inflammation, but it is unknown whether this
      inflammation starts before symptoms and in particular whether low-grade
      inflammation is present in asymptomatic neonates with reduced lung function.
      OBJECTIVE: We sought to investigate the possible association between neonatal
      lung function and biomarkers of systemic inflammation. METHODS: Plasma levels of
      high-sensitivity C-reactive protein (hs-CRP), IL-1beta, IL-6, TNF-alpha, and
      CXCL8 (IL-8) were measured at age 6 months in 300 children of the Copenhagen
      Prospective Study on Asthma in Childhood2000 birth cohort who had completed
      neonatal lung function testing at age 4 weeks. Associations between neonatal lung
      function indices and inflammatory biomarkers were investigated by conventional
      statistics and unsupervised principal component analysis. RESULTS: The neonatal
      forced expiratory volume at 0.5 seconds was inversely associated with hs-CRP
      (beta-coefficient, -0.12; 95% CI, -0.21 to -0.04; P < .01) and IL-6 (beta
      coefficient, -0.10; 95% CI, -0.18 to -0.01; P = .03) levels. The multivariate
      principal component analysis approach, including hs-CRP, IL-6, TNF-alpha, and
      CXCL8, confirmed a uniform upregulated inflammatory profile in children with
      reduced forced expiratory volume at 0.5 seconds (P = .02). Adjusting for body
      mass index at birth, maternal smoking, older children in the home, neonatal
      bacterial airway colonization, infections 14 days before, and asthmatic symptoms,
      as well as virus-induced wheezing, at any time before biomarker assessment at age
      6 months did not affect the associations. CONCLUSION: Diminished neonatal lung
      function is associated with upregulated systemic inflammatory markers, such as hs
      CRP.

PMID- 25579486
TI  - Decision making in the biological field.

PMID- 25579484
TI  - Eczema and cardiovascular risk factors in 2 US adult population studies.
AB  - BACKGROUND: Eczema is associated with high rates of sleep disturbance and quality
      of-life impairment. These factors might have a negative impact on psychosocial
      development and behavior and could increase cardiovascular risk. OBJECTIVE: We
      sought to determine whether adults with eczema have increased cardiovascular risk
      factors. METHODS: We analyzed data for 27,157 and 34,525 adults aged 18 to 85
      years from the 2010 and 2012 National Health Interview Survey. RESULTS: Adults
      with eczema had higher odds of ever smoking 100 cigarettes in their lifetime
      (survey logistic regression; adjusted odds ratio [aOR], 1.32; 95% CI, 1.18-1.47)
      and current smoking history (aOR, 1.28; 95% CI, 1.12-1.45), with significantly
      younger age of onset (survey linear regression; adjusted beta, -0.58; 95% CI, 
      0.95 to -0.21). Eczema was also associated with greater odds of ever drinking 12
      or more alcoholic beverages annually (aOR, 1.16; 95% CI, 1.03-1.31), including
      current intake of moderate (aOR, 1.33; 95% CI, 1.09-1.62) and heavier (aOR, 1.58;
      95% CI, 1.23-2.03) amounts. Adults with a history of eczema had lower odds of
      daily vigorous activity (aOR, 0.79; 95% CI, 0.63-0.99) and lower frequency of
      vigorous activity in the past week (adjusted beta, -0.46; 95% CI, -0.72 to -0.21)
      than did adults without a history of eczema. Those with eczema had a higher body
      mass index than did those without eczema (adjusted beta, 0.86; 95% CI, 0.37
      1.36), particularly a body mass index of 35 or more (aOR, 1.54; 95% CI, 1.16
      2.05), and higher odds of hypertension (aOR, 1.48; 95% CI, 1.18-1.85),
      hypertension on 2 visits (aOR, 1.56; 1.22-1.99), and lifetime prediabetes (aOR,
      1.71; 95% CI, 1.19-2.45). Finally, there were significant interactions between
      eczema and sleep disturbances such that eczema associated with fatigue, daytime
      sleepiness, or insomnia was associated with even higher odds of obesity,
      hypertension, hypertension on 2 visits, prediabetes, diabetes, and high
      cholesterol than eczema alone. CONCLUSIONS: We found that eczema in adults is a
      marker for cardiovascular risk, emphasizing the importance of behavioral
      modification and perhaps more aggressive interventions to better manage eczema.

PMID- 25579487
TI  - Boundaries of human freedom.

PMID- 25579485
TI  - Little orphan asthmas?

PMID- 25579488
TI  - Et in arcadia ego.

PMID- 25579489
TI  - Joel hildebrand.

PMID- 25579490
TI  - Sex and the brain drain.

PMID- 25579491
TI  - Science and the problem of values.

PMID- 25579492
TI  - Philips Peril: Presenting a Puzzling Paradox of Person-ness.

PMID- 25579493
TI  - Letters to and from the editor.

PMID- 25579495
TI  - Relationship between unit cell type and porosity and the fatigue behavior of
      selective laser melted meta-biomaterials.
AB  - Meta-materials are structures when their small-scale properties are considered,
      but behave as materials when their homogenized macroscopic properties are
      studied. There is an intimate relationship between the design of the small-scale
      structure and the homogenized properties of such materials. In this article, we
      studied that relationship for meta-biomaterials that are aimed for biomedical
      applications, otherwise known as meta-biomaterials. Selective laser melted porous
      titanium (Ti6Al4V ELI) structures were manufactured based on three different
      types of repeating unit cells, namely cube, diamond, and truncated cuboctahedron,
      and with different porosities. The morphological features, static mechanical
      properties, and fatigue behavior of the porous biomaterials were studied with a
      focus on their fatigue behavior. It was observed that, in addition to static
      mechanical properties, the fatigue properties of the porous biomaterials are
      highly dependent on the type of unit cell as well as on porosity. None of the
      porous structures based on the cube unit cell failed after 10(6) loading cycles
      even when the applied stress reached 80% of their yield strengths. For both other
      unit cells, higher porosities resulted in shorter fatigue lives for the same
      level of applied stress. When normalized with respect to their yield stresses,
      the S-N data points of structures with different porosities very well (R(2)>0.8)
      conformed to one single power law specific to the type of the unit cell. For the
      same level of normalized applied stress, the truncated cuboctahedron unit cell
      resulted in a longer fatigue life as compared to the diamond unit cell. In a
      similar comparison, the fatigue lives of the porous structures based on both
      truncated cuboctahedron and diamond unit cells were longer than that of the
      porous structures based on the rhombic dodecahedron unit cell (determined in a
      previous study). The data presented in this study could serve as a basis for
      design of porous biomaterials as well as for corroboration of relevant analytical
      and computational models. 

PMID- 25579496
TI  - Molecularly "wired" cholesterol oxidase for biosensing.
AB  - The influence of several factors on the activity of cholesterol oxidase (ChOx)
      transiently exposed to a room temperature ionic liquid (RTIL) was studied.
      Presence of flavin adenine dinucleotide (FAD, prosthetic group of ChOx) during
      exposure to RTIL makes the procedure enzyme-friendly, while the use of RTIL
      (green reagent) makes it environmentally-friendly. Following exposure to RTIL and
      its subsequent removal, FAD becomes part of the molecular structure of the
      refolded protein (a molecular "wire"). This makes the procedure used here a
      molecular one. The factors studied were: FAD presence in RTIL during
      modification, water presence during exposure to RTIL, and ratio FAD:RTIL during
      "wiring". Performance parameters monitored were: enzyme activity before and after
      "wiring" (expressed as (dA/dt)/mg enzyme, and measured spectrophotometrically),
      peak current in an amperometric biosensor for cholesterol detection, and
      linearity of the biosensor response depending on cholesterol concentration. After
      RTIL removal, the modified enzyme (ME) retained a high percentage of the added
      FAD, which supplemented that of the native enzyme (functioning as a "wire" and
      enhancing electron transfer kinetics), and a fraction of the initial activity.
      Used in an amperometric biosensor, ME showed catalytic activity, linear behavior
      as a function of cholesterol concentration, and stability. 

PMID- 25579497
TI  - Therapeutic potential of benzothiazoles: a patent review (2010 - 2014).
AB  - INTRODUCTION: Benzothiazole is a versatile fused heterocyclic scaffold with
      extensive pharmaceutical applications. Several benzothiazole derivatives possess
      broad spectrum of antimicrobial, analgesic, anti-inflammatory, antidiabetic
      activities and so on, and the structurally simple 2-arylbenzothiazoles are
      potential antitumor agents. Some of the compounds containing benzothiazole ring
      system are in clinical usage for the treatment of various diseases/disorders.
      AREAS COVERED: In the present review, the authors summarize inventions carried
      out towards the development of benzothiazole-based chemotherapeutic agents. It
      provides an overview of the patents filed during 2010 - 2014 pertaining to the
      anticancer, antimicrobial, anti-inflammatory and other biological activities of
      benzothiazole derivatives. EXPERT OPINION: Several molecules containing
      benzothiazole skeleton are agents of choice for the treatment of various human
      diseases/disorders. Its versatile character of being capable of serving as ligand
      to various biomolecules attracted the interest of medicinal chemists for the
      development of therapies for respective ailments, especially, the 2
      arylbenzothiazole moiety which is under development for the treatment of cancer.
      This signifies the increasing importance of benzothiazole nucleus in the area of
      drug discovery. Its structural simplicity and ease of synthesis provides scope
      for the development of chemical libraries that could serve in the discovery of
      new chemical entities progressing towards the market.

PMID- 25579498
TI  - Longitudinal relationship between metabolic syndrome and periodontal disease
      among Japanese adults aged >=70 years: the Niigata Study.
AB  - BACKGROUND: There has been little evaluation in longitudinal epidemiologic
      studies of the effect of metabolic syndrome (MetS) on periodontal status. The
      specific aim of this longitudinal study is to investigate whether MetS in the
      Japanese population could be a risk factor for periodontal disease. METHODS: A
      total of 125 older adults from Japan for whom data were available for the years
      2003 to 2006 were selected for the current study. Full-mouth periodontal status,
      measured as clinical attachment level (CAL), was recorded at baseline and in
      follow-up examinations. Development of periodontal disease was considered to be
      >=2 teeth demonstrating a longitudinal loss of proximal attachment of >=3 mm at
      the follow-up dental examination. A multivariable Poisson regression model with
      robust error variance was used to evaluate the association of MetS defined by the
      modified National Cholesterol Education Program Adult Treatment Panel III
      criteria with development of periodontal disease. Adjustments for sex, income,
      education, smoking status, number of teeth at baseline, mean CAL at baseline,
      pattern of visits to a dentist, and brushing frequency were considered. RESULTS:
      The prevalence of MetS was 21.6% (27/125). Study participants with MetS were
      approximately 2.6 times more likely to develop periodontal disease (adjusted
      relative risk 2.58, 95% confidence interval 1.17 to 5.67) after simultaneous
      adjustment for other covariates. CONCLUSIONS: These findings support the
      hypothesis that MetS may be a risk factor for periodontal disease in older
      Japanese individuals. Additional studies with larger, more diverse populations
      and more complete information are needed to substantiate the findings.

PMID- 25579502
TI  - The indirect costs of ankylosing spondylitis: a systematic review and meta
      analysis.
AB  - The aim of this systematic review was to collect and summarize all current data
      on the indirect costs related to absenteeism and presenteeism associated with
      ankylosing spondylitis. The search was conducted using Medline, Embase and Centre
      for Reviews and Dissemination databases. All collected costs were recalculated to
      average annual cost per patient, expressed in 2013 prices USD using the consumer
      price index and purchasing power parity. Identified studies were then analyzed to
      assess their possible inclusion in the meta-analysis. We identified 32 records.
      The average annual indirect cost per patient varies among all the identified
      results from US$660.95 to 45,953.87. The mean annual indirect per patient equals
      US$6454.76. This systematic review summarizes current data related to indirect
      costs generated by ankylosing spondylitis; it revealed the great economic burden
      of the disease for society. We observed a great variety of the considered
      components of indirect costs and their definitions. 

PMID- 25579503
TI  - Tuning the ferroelectric polarization in AA'MnWO6 double perovskites through A
      cation substitution.
AB  - Recent experimental and theoretical work has shown that the double perovskite
      NaLaMnWO(6) exhibits antiferromagnetic ordering owing to the Mn d states, and
      computational studies further predict it to exhibit a spontaneous electric
      polarization due to an improper mechanism for ferroelectricity [King et al.,
      Phys. Rev. B: Condens. Matter, 2009, 79, 224428; Fukushima et al., Phys. Chem.
      Chem. Phys., 2011, 13, 12186], which make it a candidate multiferroic material.
      Using first-principles density functional calculations, we investigate nine
      isostructural and isovalent AA'MnWO(6) double perovskites (A = Na, K, and Rb; A'
      = La, Nd, and Y) with the aim of articulating crystal-chemistry guidelines
      describing how to enhance the magnitude of the electric polarization through
      chemical substitution of the A-site while retaining long-range magnetic order. We
      find that the electric polarization can be enhanced by up to 150% in compounds
      which maximize the difference in the ionic size of the A and A' cations. By
      examining the tolerance factors, bond valences, and structural distortions
      (described by symmetry-adapted modes) of the nine compounds, we identify the
      atomic scale features that are strongly correlated with the ionic and electronic
      contributions to the electric polarization. We also find that each compound
      exhibits a purely electronic remnant polarization, even in the absence of a
      displacive polar mode. The analysis and design strategies presented here can be
      further extended to additional members of this family (B = Fe, Co, etc.), and the
      improper ferroelectric nature of the mechanism allows for the decoupling of
      magnetic and ferroelectric properties and the targeted design of novel
      multiferroics.

PMID- 25579504
TI  - Water balance altered in cucumber plants infected with Fusarium oxysporum f. sp.
      cucumerinum.
AB  - Fusarium wilt is caused by the infection and growth of the fungus Fusarium
      oxysporum in the xylem of host plants. The physiological responses of cucumbers
      that are infected with Fusarium oxysporum f. sp. cucumerinum (FOC) was studied in
      pot and hydroponic experiments in a greenhouse. The results showed that although
      water absorption and stem hydraulic conductance decreased markedly in infected
      plants, large amounts of red ink accumulated in the leaves of infected cucumber
      plants. The transpiration rate (E) and stomatal conductance (gs) of the infected
      plants were significantly reduced, but the E/gs was higher than healthy plants.
      We further found that there was a positive correlation between leaf membrane
      injury and E/gs, indicating that the leaf cell membrane injury increased the non
      stomatal water loss from infected plants. The fusaric acid (FA), which was
      detected in the infected plant, resulted in damage to the leaf cell membranes and
      an increase in E/gs, suggesting that FA plays an important role in non-stomatal
      water loss. In conclusion, leaf cell membrane injury in the soil-borne Fusarium
      wilt of cucumber plants induced uncontrolled water loss from damaged cells. FA
      plays a critical role in accelerating the development of Fusarium wilt in
      cucumber plants. 

PMID- 25579505
TI  - The effect of walking on risk factors for cardiovascular disease: an updated
      systematic review and meta-analysis of randomised control trials.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis of randomised control
      trials that examined the effect of walking on risk factors for cardiovascular
      disease. METHODS: Four electronic databases and reference lists were searched
      (Jan 1971-June 2012). Two authors identified randomised control trials of
      interventions >= 4 weeks in duration that included at least one group with
      walking as the only treatment and a no-exercise comparator group. Participants
      were inactive at baseline. Pooled results were reported as weighted mean
      treatment effects and 95% confidence intervals using a random effects model.
      RESULTS: 32 articles reported the effects of walking interventions on
      cardiovascular disease risk factors. Walking increased aerobic capacity (3.04
      mL/kg/min, 95% CI 2.48 to 3.60) and reduced systolic (-3.58 mm Hg, 95% CI -5.19
      to -1.97) and diastolic (-1.54 mm Hg, 95% CI -2.83 to -0.26) blood pressure,
      waist circumference (-1.51 cm, 95% CI -2.34 to -0.68), weight (-1.37 kg, 95% CI 
      1.75 to -1.00), percentage body fat (-1.22%, 95% CI -1.70 to -0.73) and body mass
      index (-0.53 kg/m(2), 95% CI -0.72 to -0.35) but failed to alter blood lipids.
      CONCLUSIONS: Walking interventions improve many risk factors for cardiovascular
      disease. This underscores the central role of walking in physical activity for
      health promotion.

PMID- 25579510
TI  - Orphans of oncology.

PMID- 25579511
TI  - The value of the systematic inflammation-based Glasgow Prognostic Score in
      patients with gastric cancer: a literature review.
AB  - The presence of a systemic inflammatory response (SIR) is recognized to occur in
      the presence of malignancy. And the SIR-Glasgow Prognostic Score (GPS)/modified
      GPS (mGPS) composed of the C-reactive protein (CRP) and albumin is a tumor stage-
      and treatment-independent, routinely available and well-standardized prognostic
      factor, reflects both an ongoing SIR (CRP) and a progressive nutritional decline
      (albumin) in patients with advanced cancer. Previous studies showed that GPS/mGPS
      appear to be a superior prognostic factor compared with other cellular components
      of the SIR and Eastern Cooperative Oncology Group performance status in some
      aspects. Besides, GPS/mGPS aids at deciding active or palliation treatment and
      selecting patients with gastric cancer who tolerate platinum-based chemotherapy.
      Therefore, GPS/mGPS may be incorporated or combined with other factors to improve
      assessment of prognosis and guide treatment of patients with gastric cancer in a
      routine clinical work. However, it remains to be determined whether the GPS and
      mGPS have different prognostic value in each stage of gastric cancer and the
      necessity of normalization of the GPS/mGPS by anti-inflammation and maintenance
      of performance status or nutritional status in clinical work. 

PMID- 25579512
TI  - Regulatory mechanisms and clinical perspectives of miR-34a in cancer.
AB  - MicroRNAs (miRNAs) are evolutionarily conserved, endogenous, noncoding RNA
      molecules of about 22-24 nucleotides in length that repress gene expression at
      the posttranscriptional level. MiR-34a plays an important role in the initiation,
      progression, and therapy of cancer. In addition, the miR-34a expression has also
      been identified as a diagnostic and prognostic cancer signature. This article
      introduces the roles of miR-34a in cancer development, metastasis as well as its
      mechanism of actions on target genes and the functional outcomes of its actions
      on radio-sensitivity. The paper ends with a brief perspective to the future of
      miR-34a. 

PMID- 25579513
TI  - Reactive oxygen species as mediator of tumor radiosensitivity.
AB  - In normal functioning of the cell, there is a balance between generation and
      neutralization of reactive oxygen species (ROS) by endogenous cellular defense
      machinery. Low levels of ROS inside the cells are required for normal functioning
      of the cell, which regulate signaling mechanisms involved in mitosis and
      apoptosis; excess of ROS production may cause oxidative stress leading to damage
      in vital cellular molecules, namely cytosolic lipids, proteins, and DNA. In the
      situation of intracellular redox imbalance, molecules of cells are altered by ROS
      leading to pathogenic state. It is to be noted that ROS is not only known to be
      involved in tumor induction and progression processes but also enhances tumor
      cell radiosensitivity. The level of ROS-mediated oxidative stress is linked to
      cellular radiosensitivity. In general, cancer cells exhibit high levels of ROS,
      which forms a target for selectively killing them by radiation. In this paper, we
      have reviewed how oxidative stress determines the radiosensitivity of tumor cells
      involving ROS in the mechanism of radiation induced tumor cell killing. It is
      suggested that radiation-induced ROS play a key role in the mechanism of tumor
      cell killing by altering the signaling network and triggering of apoptosis.
      Furthermore, it is pointed out that combined use of plant-derived antioxidants
      and radiation enhance overproduction of ROS in tumor cells leading to enhanced
      radiosensitivity, which may find practical applications in clinic. 

PMID- 25579514
TI  - Radiation induced bystander effect and DNA damage.
AB  - Bystander effects (BSEs) have been investigated for a long time but without much
      deliberation as to the cause in targeted cells and the subsequent effect in naive
      cells. BSEs have traditionally been associated with radiation. Currently, this
      phenomenon is at a juncture where nuclear DNA damage is being debated as either
      essential or nonessential. If DNA damage is essential for the bystander signal
      (BSS) production then, this raises a number of questions about, radiotherapy and
      chemotherapy of cancer patients. This review presents a detailed analysis of the
      work done to investigate nuclear DNA damage versus exclusively cytoplasmic
      targeting with ionizing radiations and measurement of bystander end-points in
      naive cells. The review also analyzes some of the research work done to
      investigate cell models that were developed specifically to study and track
      radiation-induced DNA damage to construct mutation spectra. Production of
      reactive oxygen species and reactive nitrogen species as possible candidates of
      the elusive BSS are also discussed besides the signal transduction pathways
      implicated in reception of a BSS by the naive cell. 

PMID- 25579515
TI  - Cholelithiasis, cholecystectomy and risk of hepatocellular carcinoma: a meta
      analysis.
AB  - Available evidence of the relationship between cholelithiasis, cholecystectomy,
      and risk of liver cancer and hence we conducted a meta-analysis to investigate
      the relationships. PubMed, EMBASE, and ISI Web of Knowledge were searched to
      identify all published cohort studies and case-control studies that evaluated the
      relationships of cholelithiasis, cholecystectomy and risk of liver cancer and
      single-cohort studies which evaluated the incidence of liver cancer among
      patients who understood cholecystectomy (up to February 2013). Comprehensive meta
      analysis software was used for meta-analysis. A total of 11 observational studies
      (six cohort studies and five case-control studies) were included in this meta
      analysis. The result from meta-analysis showed that cholecystectomy (risk ratio
      [RR]: 1.59, 95% confidence interval [CI]: 1.01-2.51, I2=72%) and
      cholecystolithiasis (RR: 5.40, 95% CI: 3.69-7.89, I2=93%) was associated with
      more liver cancer, especially for intrahepatic cholangiocarcinoma (ICC)
      (cholecystectomy: RR: 3.51, 95% CI: 1.84-6.71, I2=26%; cholecystolithiasis: RR:
      11.06, 95% CI: 6.99-17.52, I2=0%). The pooled standardized incidence rates (SIR)
      of liver cancer in patients who understood cholecystectomy showed cholecystectomy
      might increase the incidence of liver cancer (SIR: 1.57, 95% CI: 1.13-2.20,
      I2=15%). Based on the results of the meta-analysis, cholecystectomy and
      cholecystolithiasis seemed to be involved in the development of liver cancer,
      especially for ICC. However, most available studies were case-control studies and
      short-term cohort studies, so the future studies should more long-term cohort
      studies should be well-conducted to evaluate the long-term relationship.

PMID- 25579516
TI  - Grading systems in the cytological diagnosis of breast cancer: a review.
AB  - In developing countries, diagnosis of breast carcinoma is still made on fine
      needle aspiration cytology (FNAC). For the resource-poor settings, FNAC is
      cheaper, less invasive and can sample different areas of the lesion compared with
      core needle biopsy. The role of breast FNA is usually limited to just categorize
      the lesion as benign or malignant. Prognostic information from cytomorphology,
      conveyed to the clinician depends upon the cytopathologist's way of formatting
      the report. PubMed-based literature search collated the information from articles
      describing the architectural and cytological features studied on breast
      aspiration smears. This review focuses on cytomorphological features and the
      different grading systems with their strengths, short-comings, and practical
      applicability. Eight worldwide articles proposing new methods of grading the
      cytological smears from breast cancers were published between 1980 and 2006. All
      the grading methods were developed for the most common type of breast cancer,
      that is, infiltrating duct carcinoma (not otherwise specified) type, and most of
      the workers used Papanicolaou-stained smears for the purpose of grading.
      Moreover, if interpreted carefully FNAC smears can convey information on most of
      the histological features. Hence, in developing countries, the focus should be on
      extracting the maximum information from cytological smears, so that a more
      precise "surgical pathology" type diagnosis can be given, instead of merely
      reporting as benign or malignant. Among all the discussed grading systems, we
      suggest grading system by Howell would be most appropriate and closest to the
      accepted histologic grading system as it applies Scarff-Bloom-Richardson
      histological grading system with modifications on FNA smears. We recommend it to
      be followed by all cytopathologists, in order to bring uniformity in the
      reporting of breast FNAs for grading the malignant lesions. 

PMID- 25579517
TI  - Cancer stem cells: an insight and future perspective.
AB  - The cancer stem cell (CSC) concept derives from the fact that cancers are
      dysregulated tissue clones whose continued propagation is vested in a
      biologically distinct subset of cells that are typically rare. Rare CSCs have
      been isolated from a number of human tumors, including hematopoietic, brain,
      colon, and breast cancer. With the growing evidence that CSCs exist in a wide
      array of tumors, it is becoming increasingly important to understand the
      molecular mechanisms that regulate self-renewal and differentiation because
      corruption of genes involved in these pathways likely participates in tumor
      growth. Understanding the biology of CSCs will contribute to the identification
      of molecular targets important for future therapies. 

PMID- 25579518
TI  - An overview of doxorubicin formulations in cancer therapy.
AB  - The burden of cancer is continuously increasing, and is rapidly becoming a global
      pandemic. The first liposomal encapsulated anticancer drug which received
      clinical approval against malignancies including solid tumours, transplantable
      leukemias and lymphomas was Doxorubicin HCl. This review is aimed at providing an
      overview of doxorubicin in cancer therapy. Pegylated liposomal doxorubicin has a
      polyethylene glycol (PEG) layer around doxorubicin-containing liposome as the
      result of a process known as pegylation. Non-pegylated liposomal doxorubicin
      (NPLD) was developed to overcome the drawbacks associated with previous
      formulations. Nudoxa; (NPLD) with its unique drug delivery system offers the
      benefit of pegylated liposomal doxorubicin without hand foot syndrome as the
      major side effect. Future studies will be directed towards estimating the costs
      of treatment with the novel liposomal doxorubicin formulations in order to assess
      their widespread use and robustness in treating patients with cancer. 

PMID- 25579519
TI  - Effect of statins on gastric cancer incidence: a meta-analysis of case control
      studies.
AB  - INTRODUCTION: Gastric cancer is among the leading causes of cancer-related death
      worldwide, especially in Eastern Asia, Eastern Europe and South America. Statin
      is one of the most widely used medications for hypercholesterolemia. Several meta
      analyses have failed to determine the relationship between statins and gastric
      cancer. AIMS: A meta-analysis of case control studies is conducted to evaluate
      the association of statin exposure and risk of gastric cancer. MATERIALS AND
      METHODS: Eight electronic databases (The Cochrane Central Register of Controlled
      Trials (CENTRAL) (Issue 12, 2012), PubMed, EMBASE, ISI Web of Knowledge, CNKI,
      CBM, CSJD and Wanfang Database) were searched for relevant publications through
      September 2013. Two reviewers determined the eligibility of articles and
      abstracted the data independently. RevMan 5.2 software was used for statistical
      analysis. RESULTS: 146 items were retrieved from the databases and 6 studies were
      identified in this meta-analysis, which included 5,993 cases and 54,800 matched
      controls. RESULTS from the meta-analysis demonstrated that statins were inversely
      related to the risk of gastric cancer (RR=0.56, 95% CI: 0.35-0.90). There was no
      significant difference for cumulative duration of statin exposure and gastric
      cancer, nor participants from Asia, Europe, or USA. CONCLUSION: This meta
      analysis suggests that statins have favorable effects on gastric cancer,
      rigorously designed and executed observational studies and randomized control
      trials with longer duration of follow-up are warranted to determine effects in
      clinical practice.

PMID- 25579520
TI  - Epirubicin, oxaliplatin, and capectabine is just as "MAGIC"al as epirubicin,
      cisplatin, and fluorouracil perioperative chemotherapy for resectable locally
      advanced gastro-oesophageal cancer.
AB  - BACKGROUND: The perioperative use of epirubicin, cisplatin, and fluorouracil
      (ECF) significantly improves outcomes in patients with gastric and gastro
      oesophageal (GO) cancers but is cumbersome to administer. Given the equivalence
      of epirubicin, oxaliplatin, and capectabine (EOX) with ECF in advanced setting,
      we analyzed the compliance, efficacy, and toxicity of perioperative EOX in
      resectable but locally advanced cancers. METHODS: This is a retrospective
      analysis of prospectively maintained database of patients treated between January
      2012 and September 2013 at Tata Memorial Centre. Patients were planned to receive
      3# of neoadjuvant (NA) and 3# of adjuvant EOX (intravenous epirubicin 50 mg/m 2
      D1, oxaliplatin 130 mg/m 2 , on D1, capecitabiine 1250 mg/m 2 D1-21) every 21
      days. On completion of NA therapy, patients were planned to undergo gastrectomy
      and D2 lymphadenectomy. RESULTS: A total of 99 patients (76% males, median age 51
      years) were treated with perioperative EOX. Preoperatively, 93% patients
      completed EOX. Post-NA chemotherapy, 4 patients progressed, 1 patient died and 94
      were taken up for surgery. Of these, 9 were inoperable and 85 patients underwent
      radical surgery. Of these, 71% (60/85) were able to complete three cycles of
      adjuvant EOX. The compliance to complete all 6 cycles of perioperative
      chemotherapy was 64%. Grade 3 and 4 toxicities were comparable to the MAGIC
      dataset apart from higher number of diarrhea in our patients. CONCLUSIONS: In
      patients with resectable GO adenocarcinoma, it is possible to deliver the MAGIC
      type perioperative chemotherapy with EOX with better compliance, toxicity, and
      efficacy rates.

PMID- 25579521
TI  - Dosimetric comparison between Volumetric Modulated Arc Therapy (VMAT) vs
      Intensity Modulated Radiation Therapy (IMRT) for radiotherapy of mid esophageal
      carcinoma.
AB  - AIMS: Dosimetric comparison of VMAT with IMRT in middle third esophageal cancer
      for planning target volume (PTV) and organs at risk (OAR). MATERIALS AND METHODS:
      Ten patients in various stages from I-III were inducted in the neo-adjuvant
      chemoradiation protocol for this study. The prescribed dose was 4500 cGy in 25
      fractions. Both VMAT and IMRT plan were generated in all cases and Dose Volume
      Histogram (DVH) comparative analysis was performed for PTV and OAR. Paired t-test
      was used for statistical analysis. RESULTS: The PTV Dmean and D95 in IMRT and
      VMAT plan were 4566.6+/-50.6 cGy vs 4462.8+/-81.8 cGy (P=0.1) and 4379.8+/-50.6
      cGy Vs 4424.3+/-109.8 cGy (P=0.1), respectively. The CI and HI for PTV in IMRT vs
      VMAT plans were 0.96+/-0.02 vs 0.97+/-0.01 (P=0.4) and 10.58+/-3.07 vs 9.45+/
      2.42 (P=0.2), respectively. Lung doses for VMAT vs IMRT were 4.19 vs 2.59%
      (P=0.03) for V35-7.63 vs 4.76% (P=0.01) for V30-13.6 vs 9.98% (P=0.01) for V25
      24.77 vs 18.57% (P=0.04) for V20-46.5 vs 34.73% (P=0.002) for V15. The Mean Lung
      Dose (MLD) was reduced by VMAT technique compared to IMRT; 1524.6+/-308.37 cGy
      and 1353+/-186.32 cGy (P=0.012). There was no change in Dmax to spinal cord in
      both the techniques. There was a dose reduction by VMAT compared to IMRT to the
      heart but it was statistically insignificant; V35-6.75% vs 5.55% (P=0.223); V30
      12.3% vs 10.91% (P=0.352); V25-21.81% vs 20.16% (P=0.459); V20-38.11% vs 32.88%
      (P=0.070); V15-61.05% vs 54.2% (P=0.10). CONCLUSION: VMAT can be a better option
      in treating mid esophageal carcinoma as compared to IMRT. The VMAT plans resulted
      in equivalent or superior dose distribution with a reduction in the dose to lung
      and heart.

PMID- 25579522
TI  - The usefulness of diffusion-weighted magnetic resonance imaging in bladder cancer
      staging and functional analysis.
AB  - AIM: We assessed the effect of adding diffusion-weighted magnetic resonance
      imaging (DW-MRI) to conventional MRI for T staging and the correlation between
      apparent diffusion coefficient (ADC) values and clinicopathological parameters
      for patients with bladder cancer. MATERIALS AND METHODS: We retrospectively
      reviewed the records of 160 patients with bladder cancer who underwent MRI at our
      institute. All patients were routinely assessed with conventional MR imaging.
      Since January 2008, we added DW-MRI. RESULTS: In these 160 patients, 127 (79.4%)
      tumors were detectable by MRI. In all patients with detectable tumors, on a stage
      by-stage basis, 96 (75.6%) of 127 patients received the correct diagnosis. With
      DW-MRI, accurate diagnosis was obtained in 80 (80.0%) of 100 cases; without DWI
      in only 16 (59.3%) of 27 cases (P=0.026). For T staging, the accuracy for
      distinguishing muscle invasion (T?1 vs T?2) with DW-MRI (83.0%) was superior to
      that without DW-MRI (66.7%). The accuracy for distinguishing perivesical fat
      invasion (T?2 vs T?3) with DW-MRI (98.0%) was also superior to that without DW
      MRI (92.6%). The ADC values were significantly related with tumor diameter (<3 cm
      vs ?3 cm, P<0.001), histopathological grade (low grade vs high grade, P<0.001), T
      stage (?T1 vs ?T2, P<0.001), and operative method (transurethral resection vs
      total cystectomy, P<0.001). CONCLUSIONS: We demonstrated that DW-MRI is not only
      useful for bladder cancer T staging, but also a prognostic factor for patients
      with bladder cancer.

PMID- 25579523
TI  - Is volumetric modulated arc therapy (RapidArc) better than intensity modulated
      radiotherapy for gynecological malignancies? A dosimetric comparison.
AB  - AIMS: Evaluation of the dosimetric advantage, if any, of RapidArc (double arc and
      triple arc [DA and TA]) over standard fixed field intensity-modulated radiation
      therapy (IMRT) in gynecologic malignancies. MATERIALS AND METHODS: A total of 20
      cases of gynecologic malignancies were included. Static IMRT sliding window,
      single arc (SA), DA and TA plans were generated with eclipse planning system. The
      prescribed dose was 50.4 Gy/28# to the planning target volumes. RESULTS: IMRT
      provided target coverage equivalent to DA and inferior to TA (D95% [in Gy]-
      49.94, 49.58, 49.96, 50.17 for IMRT, SA, DA and TA respectively--all observations
      in the same sequence). Conformity index 90 (CI 90 (0.964, 0.927, 0.918, 0.822)
      and homogeneity index (0.0683, 0.119, 0.098, 0.097) of IMRT were superior. TA was
      superior to other arcs in all parameters except CI 90 (P=0.805) and bladder dose
      (lower in DA). Rectal, bladder and bowel sparing was best achieved with IMRT
      followed by TA; bilateral femur dose was lower in arcs. The total monitor units
      and treatment time of arcs were significantly lower than IMRT, reduced by a
      factor of 2.41-2.59 and 3.2-3.5 respectively (All P values significant).
      CONCLUSION: IMRT provided better overall plan for gynecologic malignancies with
      lower organs at risk dose and target coverage equivalent to DA and TA. Treatment
      delivery efficiency was higher with RapidArc. The TA plan is dosimetrically
      superior to DA, but the gain is small. The decision whether or not to add a third
      arc for a small gain should be individualized.

PMID- 25579524
TI  - Clinical and cosmetic results of breast boost radiotherapy in early breast
      cancer: a randomized study between electron and photon.
AB  - INTRODUCTION: Breast-conserving surgery followed by radiation therapy (RT) to the
      intact breast is now clearly established as the most acceptable strategy for
      women with early-stage invasive breast cancer. Recommended techniques for
      radiotherapy is whole breast irradiation (WBI) followed by boost to the tumor
      bed. AIMS: The aim of this study is to compare the modalities of three
      dimensional conformal RT (3DCRT) and electron beam therapy as boost in post
      lumpectomy patients of early stage breast cancer, following WBI. MATERIALS AND
      METHODS: The study comprised of selecting 50 patients of early-stage post
      lumpectomy breast cancer. Each patient was initially treated by WBI (40 Gy in 16
      fractions) and then followed by tumor bed boost (16 Gy in 8 fractions) with
      either electron beam therapy or with photon (3DCRT), 25 patients in each arm.
      Patients were evaluated regularly for acute and chronic radiation toxicities,
      cosmesis, and pattern of failure. Dosimetric comparison of the plans was also
      done. RESULTS: Median age of the patients was 42 years with 66% being
      premenopausal. Median duration of follow-up was 23 months. In arm A (electrons),
      two patients had grade III-IV reactions at treatment completion with one patient
      required RT interruption. Whereas, in arm B (3DCRT), five patients had grade III
      IV reactions at treatment completion with three patients required RT
      interruption. At 6 months and 2 years follow-up, both the arms had almost similar
      skin, subcutaneous toxicity, and cosmetic score. At the end of 2 years, there
      were totally four failures among 50 patients, with one locoregional failure in
      both arms (4%). Dosimetric analysis revealed that conformality (radiation
      conformity index (RCI)), dose homogeneity index (DHI) and planning target volume
      (PTV) coverage was significantly better in 3DCRT boost plans. Organs at risk
      (OAR) dosimetry also revealed significant decrease in ipsilateral lung and heart
      doses with 3DCRT plans in which tangential or oblique fields were used; and
      whereas in electron beam, only single direct fields were used. CONCLUSIONS: Both
      electrons and 3DCRT can be used for boost planning to the tumor bed in post
      lumpectomy patients. Though there was slightly increased acute skin toxicity with
      3DCRT photon which led to interruption of therapy, overall cosmesis at 2 years is
      similar in both modalities. 3DCRT boost is a better option than electrons
      dosimetrically, considering the fact that conformality; PTV coverage and OAR
      dosimetry were superior with photons. Thus in centers where electron beam therapy
      is not available, 3DCRT photon can be used effectively for tumor bed boost.

PMID- 25579525
TI  - A Monte Carlo approach to lung dose calculation in small fields used in intensity
      modulated radiation therapy and stereotactic body radiation therapy.
AB  - AIMS: In the current study, the effect of electronic disequilibrium on lung dose
      with small photon beams was verified. MATERIALS AND METHODS: The central axis
      absorbed dose in lung phantom was calculated by Monte Carlo (MC) method. The 6
      and 18 MV photon beams of Varian Clinac 2100EX were simulated using MCNPX MC Code
      (Los Alamos national lab, USA). The MC model was used to calculate the depth
      doses water and low density water resembling the soft-tissue and lung,
      respectively. Four small field sizes including 0.5 cm2*0.5 cm2, 1 cm2*1 cm2, 2
      cm2*2 cm2, and 3 cm2*3 cm2 were used in this study. RESULTS: Percentage of dose
      reduction in lung region relative to homogenous phantom for 6 MV photon beam were
      44.6%, 39%, 13%, and 7% for 0.5 cm2*0.5 cm2, 1 cm2*1 cm2, 2 cm2*2 cm2, and 3
      cm2*3 cm2 fields, respectively. For 18 MV photon beam, the results were found to
      be 82%, 69%, 46%, and 25.8% for the same field sizes, respectively. The solid
      tumor dose inside lung was reduced considerably between 17% and 35% for 18 MV
      beam, while there was only 9% dose reduction for tumor dose for 0.5 and 1 cm
      field sizes. CONCLUSION: Our study showed that the dose reduction with small
      fields in the lung was very enormous. Thus, inaccurate prediction of absorbed
      dose inside lung and also lung soft-tissue interfaces with small photon beams may
      lead to critical consequences for treatment outcome.

PMID- 25579526
TI  - Assessing oral cancer knowledge and awareness among Malaysian dental and medical
      students.
AB  - BACKGROUND: Oral cancer is a foremost health dilemma in several regions of the
      world. General dental practitioners and general medical practitioners play a
      major role in recognition of oral mucosal changes that may lead to malignancy.
      Their knowledge in oral cancer itself and the risk factors associated with the
      disease need to be sufficient. OBJECTIVE: The objective of the present study was
      to investigate awareness and knowledge of undergraduate dental and medical
      students in early detection and prevention of oral cancer. MATERIALS AND METHODS:
      Dental and medical students were invited to participate by answering a
      questionnaire on their habits of the oral mucosa examination and history taking,
      knowledge on risk factors and changes related with oral cancer, referral of
      patients as well as their desire to receive further information on oral cancer.
      Chi-square test was carried out to analyze knowledge and awareness between
      undergraduate dental and medical students. RESULTS: Undergraduate dental students
      were more likely to examine oral mucosa (96.7%) and advice risk habits to
      patients (93.9%) compared to medical students (60.6% and 79.8% respectively).
      Significantly more dental students considered smoking (84.4%), betel quid chewing
      (76.1%), and alcohol drinking (35%) as risk factors. Clinical changes of oral
      cancer were better identified by dental students (leukoplakia-52.8%,
      erythroplakia-45%, and non-healing ulcer-40%) compared to medical students
      (leukoplakia-12.9%, erythroplakia-4.6%, and non-healing ulcer-10.3%). Both dental
      and medicals students reported the desire to receive further information in
      relation to oral cancer. CONCLUSION: Dental students have better knowledge and
      awareness in prevention and early detection of oral cancer compared to medical
      students.

PMID- 25579527
TI  - Oral squamous cell carcinoma in a South African sample: Race/ethnicity, age,
      gender, and degree of histopathological differentiation.
AB  - OBJECTIVES: The purpose of this retrospective study was to investigate
      differences between black and white persons with oral squamous cell carcinoma
      (OSCC) with regard to age, gender, oral site affected, and histopathological
      degree of differentiation; and to compare these clinicopathological parameters
      between persons younger and older than 40 years in a South African population
      sample from the greater Johannesburg area. MATERIAL AND METHODS: The
      histopathological reports of 510 cases of OSCC during the period 1995-2002 were
      retrospectively evaluated, and the data regarding age, gender, ethnicity/race,
      oral site affected, and degree of histopathological differentiation were recorded
      and statistically analyzed for differences between black and white persons, and
      between persons younger and older than 40 years of age. RESULTS: Statistically
      significantly, black persons were diagnosed with OSCC at a younger mean age (57
      years) than white persons (61 years) (P=0.0086). The difference between male:
      female (M:F) ratio in black (3.74:1) and white persons (1.96:1) was statistically
      significant (P=0.0041). White persons had a significantly higher proportion of
      SCC of the lower lip than black persons (P<0.0001). CONCLUSION: OSCC was
      diagnosed at a younger age in black than in white persons; the proportion of
      black males in the black population group was greater than that of white males in
      the white population group; and the proportion of SCC of the lips was higher in
      younger than in older persons.

PMID- 25579528
TI  - Management of brain metastases from non-small cell lung cancer.
AB  - PURPOSE: The purpose of the following study is to evaluate the treatment
      modalities, clinical status and prognostic factors affecting survival rates in
      patients with newly diagnosed brain metastasis from non-small cell lung cancer
      (NSCLC). PATIENTS AND METHODS: NSCLC patients with a new diagnosis of one to four
      brain metastasis evaluated retrospectively for the effects of treatment regimens
      on local failure-relapse-free survival (LRFS) and overall survival (OS). The
      relationship between age, gender, performance status, recursive partitioning
      analysis (RPA) classification, the primary tumor under control, number of
      metastatic tumors in the brain and total volume of brain metastasis and prognosis
      is analyzed. RESULTS: Out of a total of 138 (121 male and 17 female) patients,
      nearly 44.2% received only gamma-knife (GK); 24.6% were received both GK and
      whole brain radiotherapy (WBRT), 2.9% had GK and surgery, 3.6% received GK,
      surgery and WBRT, 10.9% had surgery and WBRT and 12.3% received only WBRT for
      treatment. Median LRFS of surgery plus WBRT group was significantly higher when
      compared with WBRT group (P<0.0001). The OS was significantly longer for surgery
      plus WBRT group than the other treatment groups (P=0.037). When median survival
      of WBRT-only group compared with surgery plus WBRT, it was significantly higher
      (29.6 months vs. 16.7 months, P=0.006). Median OS of surgery plus WBRT group was
      significantly higher than GK plus WBRT group (29.6 months vs. 9.3 months,
      P=0.007). CONCLUSION: WBRT is still the most effective treatment method following
      surgery in selected patients according to their age, performance status and
      spread of the primary disease with NSCLC had limited number brain metastasis.
      Adding WBRT treatment after surgery significantly improved OS and LRFS.

PMID- 25579529
TI  - Prognostic significance and predictive performance of volume-based parameters of
      F-18 FDG PET/CT in squamous cell head and neck cancers.
AB  - AIM: It has been previously reported that metabolic tumor volume on positron
      emission tomography-computed tomography predicts disease recurrence and death in
      head-and-neck cancer. In this study, we assessed the prognostic value of
      metabolic tumor volume measured using F18-Fluorodeoxyglucose PET/CT in patients
      with head and neck squamous cell carcinoma. MATERIALS AND METHODS: We analyzed
      the imaging findings of 74 patients (age 57+/-16) retrospectively, with head and
      neck cancer who underwent PET/CT scan for staging and after treatment. Forty-tree
      patients had nasopharynx, 15 patients had hypopharynx, 9 patients had larynx, and
      7 patients had oropharynx cancer. The MTVs of primary sites with or without lymph
      nodes were measured, and outcomes were assessed using the treatment response
      evaluation by the Response Evaluation Criteria in Solid Tumors and recurrence
      events during follow-up. RESULTS: A total of 48 patients had complete response or
      no recurrence was detected as of in the last follow-up. Of the first PET/CT scan,
      the median primary tumor SUVmax was 18.8 and the median nodal SUVmax was 13.4.
      The median primary tumor MTV% 50s ranged from 11.12 cm3 to 16.28 cm3, and the MTV
      after the therapy ranged from 1.18 cm3 to 3.51 cm3. CONCLUSION: Metabolic tumor
      volume (MTV) represents tumor burden, which shows F18-Fluorodeoxyglucose uptake
      and has a potential value in predicting short-term outcome and disease-free
      survival in patients with head and neck cancer.

PMID- 25579530
TI  - MRI diagnosis of intradural extramedullary tumors.
AB  - OBJECTIVE: This study evaluates the magnetic resonance imaging (MRI)
      manifestation of intradural extramedullary (IDEM) tumors to improve the imaging
      diagnostic level. MATERIALS AND METHODS: From January 2005 to December 2012, a
      retrospective analysis of the MRI examination was performed on 108 patients with
      IDEM tumors confirmed by surgical pathology postoperatively in our hospital.
      According to the pathological classification; the gender, age, location, size,
      foraminal state extension, signal intensity (compared with the spinal cord), and
      enhancement were recorded and statistically analyzed. RESULTS: A total of 108
      cases (111 lesions) were reported; 69 (70 lesions), 31 (31 lesions), three (five
      lesions), four (four lesions), and one (one lesion) of which were schwannoma,
      meningioma, neurofibroma, teratoma, and metastatic tumor, respectively. MRI
      manifestations of different IDEM tumors have certain specificities. CONCLUSION:
      MRI is the preferred examination method for to diagnose IDEM tumors and provide a
      reliable imaging basis for clinical treatment and prognosis judgment.

PMID- 25579531
TI  - A comparison between four immobilization systems for pelvic radiation therapy
      using CBCT and paired kilovoltage portals based image-guided radiotherapy.
AB  - INTRODUCTION: We commonly use 6- and 4-clamped thermoplastic molds (TMs) for
      rigid immobilization during pelvic radiotherapy (RT), sometimes a vacuum cushion
      (VC) is also used as leg support with TM. Our objective was to report the setup
      margins (SMs) associated with the different systems, to analyze whether any of
      these systems is superior, and to analyze whether any of them showed better
      reproducibility in any particular direction. MATERIALS AND METHODS: Retrospective
      analysis was done by dividing the patients into four groups: 6-clamp with VC
      (6CVC), 6-clamp without VC (6CNC), 4-clamp with VC (4CVC), and 4-clamp without VC
      (4CNC). A repeat offline review was done for all patients and errors were
      tabulated. Statistical methods were then applied. RESULTS: Total 24 patients had
      413 image-guided RT (IGRT) sessions, 312 were cone beam computed tomography scan
      (CBCT) scans and 101 were paired kilovoltage portals (kVp). There was no
      statistically significant difference between 6CVC and 6CNC. However, while
      comparing 4CVC and 4CNC, a statistically significant difference was seen in all
      directions. VC improved precision in vertical and lateral direction mainly, while
      the 6-clamped TM improved reproducibility in longitudinal direction. CONCLUSIONS:
      SM was low for all the four immobilization systems studied. There is no added
      benefit of using a VC with 6-clamped TM for pelvic RT. Use of a VC is recommended
      with 4-clamped TM to improve overall reproducibility. 6-clamped TM helps keep the
      errors low.

PMID- 25579532
TI  - A comparative study of set up variations and bowel volumes in supine versus prone
      positions of patients treated with external beam radiation for carcinoma rectum.
AB  - PURPOSE: A prospective study was undertaken to evaluate the influence of patient
      positioning on the set up variations to determine the planning target volume
      (PTV) margins and to evaluate the clinical relevance volume assessment of the
      small bowel (SB) within the irradiated volume. MATERIALS AND METHODS: During the
      period of months from December 2011 to April 2012, a computed tomography (CT)
      scan was done either in supine position or in prone position using a belly board
      (BB) for 20 consecutive patients. All the patients had histologically proven
      rectal cancer and received either post- or pre-operative pelvic irradiation.
      Using a three-dimensional planning system, the dose-volume histogram for SB was
      defined in each axial CT slice. Total dose was 46-50 Gy (2 Gy/fraction),
      delivered using the 4-field box technique. The set up variation of the study
      group was assessed from the data received from the electronic portal imaging
      device in the linear accelerator. The shift along X, Y, and Z directions were
      noted. Both systematic and random errors were calculated and using both these
      values the PTV margin was calculated. RESULTS: The systematic errors of patients
      treated in the supine position were 0.87 (X-mm), 0.66 (Y-mm), 1.6 (Z-mm) and in
      the prone position were 1.3 (X-mm), 0.59 (Y-mm), 1.17 (Z-mm). The random errors
      of patients treated in the supine positions were 1.81 (X-mm), 1.73 (Y-mm), 1.83
      (Z-mm) and in prone position were 2.02 (X-mm), 1.21 (Y-mm), 3.05 (Z-mm). The
      calculated PTV margins in the supine position were 3.45 (X-mm), 2.87 (Y-mm), 5.31
      (Z-mm) and in the prone position were 4.91 (X-mm), 2.32 (Y-mm), 5.08 (Z-mm). The
      mean volume of the peritoneal cavity was 648.65 cm 3 in the prone position and
      1197.37 cm 3 in the supine position. CONCLUSION: The prone position using BB
      device was more effective in reducing irradiated SB volume in rectal cancer
      patients. There were no significant variations in the daily set up for patients
      treated in both supine and prone positions.

PMID- 25579533
TI  - Irradiation doses on thyroid gland during the postoperative irradiation for
      breast cancer.
AB  - PURPOSE: Thyroid gland is one of the radiosensitive endocrine organs in the body.
      It has been shown that direct irradiation of thyroid with total doses of 26 to 30
      Gy can lead to functional abnormalities. In this study, irradiation doses on
      thyroid gland of the patients who received postoperative chest-wall/breast and
      regional nodal irradiation were assessed. MATERIALS AND METHODS: Retrospective
      analyses of treatment plans from 122 breast cancer patients who were treated with
      3D conformal radiotherapy (3D CRT) planning was performed. All patients received
      irradiation to supraclavicular/level III lymph nodes in addition to chest
      wall/breast. A total dose of 46 Gy was delivered in 25 days to
      supraclavicular/level III lymph node region while a total dose of 50 Gy was
      delivered to whole breast/chest-wall. Thyroid gland was contoured on 2-5 mm
      thickness of computed tomography scans. Absolute thyroid volume, mean thyroid
      doses were calculated. RESULTS: The mean thyroid volume of all patients was 16.7
      cc (min: 1.9 cc, max: 41.6 cc). The mean irradiation dose on was 22.5 Gy (0.32 Gy
      46.5 Gy). The level of dose was higher than 26 Gy in 44% of the patients.
      CONCLUSIONS: In majority of the node-positive breast cancer patients treated with
      3D CRT, the thyroid gland was exposed to considerable doses. On the other hand,
      for 44% of the patients are at risk for developing thyroid function abnormalities
      which should be considered during the routine follow-up.

PMID- 25579534
TI  - Primary extranodal non-Hodgkin's lymphoma of oral cavity--a single centre
      retrospective study.
AB  - BACKGROUND: Extra nodal involvements of non-Hodgkin's lymphomas (NHL) are not so
      uncommon, but the involvement of oral cavity by NHL is very rare. MATERIALS AND
      METHODS: The present study involved retrospective analysis of patients from year
      2001 to 2011, who presented with oral mass and on evaluation were diagnosed to
      have primary extranodal NHL of oral cavity at a tertiary cancer care centre in
      South India. RESULTS: There were seven patients treated for primary NHL of oral
      cavity at our institute in last 10 years. The median age at presentation was 43.2
      years (range 29-65 years). There were five males and two females. Oral tongue was
      the most common site (three patients) followed by alveolus (two patients). The
      other sites of involvement included gingivobuccal sulcus in one patient and hard
      palate in one patient. All patients were initially evaluated at oral oncology
      department for gradually increasing ulcerative mass in oral cavity. None of the
      patients had B symptoms. In our study, plasmablastic lymphoma was the most common
      type of NHL, followed by diffuse large B cell lymphoma (DLBCL) and peripheral T
      cell lymphoma, not otherwise specified (PTCL, NOS). Out of seven patients, two
      were HIV positive, both having plasmablastic lymphoma. Four out of the seven
      patients received a combination of chemotherapy and radiotherapy and three
      patients received only chemotherapy. Only three patients could complete the
      prescribed chemotherapy and radiotherapy schedule and were alive and diseases
      free with a median follow-up of 21 months. CONCLUSION: Involvement of oral cavity
      by lymphoma is rare. Plasmablastic lymphoma was the most common oral cavity NHL
      in our patients. Although number of cases in present study was less, our data
      suggests that oral NHL has aggressive course with less favorable outcome. Further
      large sample studies incorporating rituximab-based chemotherapy and more
      aggressive chemotherapy for plasmablastic lymphoma will be helpful for better
      understanding of treatment outcome.

PMID- 25579535
TI  - Radiation therapy for clinically localized prostate cancer: long-term results of
      469 patients from a single institution in the era of dose escalation.
AB  - AIMS: The aim of the following study is to analyze the long-term results of
      veterans treated with dose escalated radiation therapy for prostate cancer.
      MATERIALS AND METHODS: This retrospective study analyzed 469 patients who were
      treated between 2003 and 2010 with dose escalated radiation therapy to a minimum
      dose of 7560 cGy for prostate cancer at the New York Harbor Department of
      Veterans Affairs. Biochemical failure-free survival (bFFS) and distant metastatic
      free survival (DMFS) were compared using the Kaplan-Meier method. Univariate and
      multivariate Cox Regression were used to measure the impact of covariates on
      biochemical control. RESULTS: The median follow-up was 61 months and 95.3% of
      patients were followed at least 2 years. The 5-year bFFS for National Cancer Care
      Network low, intermediate and high risk disease were 90.3%, 86.9% and 77.3%
      respectively (P=0.001). Patients with high risk disease were more likely to
      develop metastatic disease. The 5-year DMFS was 99.1% for low risk, 98.8% for
      intermediate risk and 94.5% for high-risk (P<0.001). There were 8 prostate cancer
      related deaths, of which 6 had high risk disease and 2 had intermediate risk
      disease. The 5-year prostate cancer specific survival was 98.4%. Toxicities were
      generally mild, however there were two genitourinary toxicity related deaths,
      though in both patients there were confounding medical issues that may have
      contributed to their deaths. CONCLUSIONS: Dose escalated radiation in the
      treatment of United States Veterans appears to be well-tolerated with results in
      line with prior reports. Further follow-up is necessary to identify any
      additional late toxicities as well as to assess the durability of their
      biochemical control beyond 5 years.

PMID- 25579536
TI  - Perineural space invasion in cervical cancer (FIGO IB1-IIB) accompanied by high
      risk factors for recurrence.
AB  - BACKGROUND: Perineural space invasion (PSI) represents a poor prognostic factor
      in various carcinomas. Studies on PSI in cervical cancer patients are scarce and
      report discrepant results regarding its incidence and prognostic value. AIMS: The
      aim of the following study was to evaluate the occurrence rate and prognostic
      significance of parametrial PSI in patients cervical cancer (FIGO IB1-IIB),
      accompanied by high-risk factors for recurrence. MATERIALS AND METHODS: We
      reviewed clinical records and pathology slides of patients with cervical cancer
      after radical hysterectomy. Only patients with at least one of following factors:
      Depth of invasion of >=15 mm, parametrial and lymph node involvement, were
      enrolled in the study. RESULTS: A total of 50 patients fulfilled the above
      mentioned criteria. Parametrial PSI was found in 9 (18%) patients (Group I),
      whereas the remaining 41 (82%) subjects constituted group II. The presence of PSI
      proved to correlate with the depth of invasion of >=15 mm (P=0.006) and tumor
      size of >=40 mm (P=0.01), as well as a more advanced stage of the disease
      (P=0.04). No statistically significant differences in recurrence-free survival
      rate between the two groups were observed. CONCLUSIONS: We were able to correlate
      parametrial PSI with the depth of invasion, tumor size and more advanced stage of
      the disease in early-stage cervical cancer with high-risk of recurrence. No
      association with a worse prognosis was observed.

PMID- 25579537
TI  - Depression, anxiety and quality of life through the use of complementary and
      alternative medicine among breast cancer patients in Turkey.
AB  - BACKGROUND AND AIM: Breast cancer is the most common type of cancer amongst women
      today. The aim of this study was to examine the association between complementary
      and alternative medicine (CAM) and the quality of life (QoL), anxiety and
      depression and demographic characteristics of women with breast cancer. MATERIALS
      AND METHODS: QoL was measured by the European Organization for Treatment and
      Research of Cancer quality of life core questionnaire (QLQ-C30, version 3.0) and
      anxiety and depression was measured by the hospital anxiety and depression scale.
      RESULTS: In total, 122 patients with breast cancer were enrolled in the study and
      50% (n=61) of them reported that they were using CAM. The most commonly used CAM
      methods were stinging nettle (57%) and prayer and spiritual healing (49%). No
      relationship was found between the use of CAM and the patient's age, time to
      diagnosis, cancer stage, chemotherapy use, smoking and residence. However, the
      analyses showed a positive association between CAM and role functioning (P=0.014)
      and financial difficulties (P=0.011); and a negative association between CAM and
      emotional functioning (P=0.033). CONCLUSIONS: Based on the previous studies, 20
      83.3% of breast cancer patients among different countries and cultures used CAM.
      Our results suggested that the use of CAM among women is quite popular, but they
      showed no correlation between CAM usage and anxiety and depression. In addition,
      CAM usage was more common in breast cancer patients with a poor emotional and
      financial status.

PMID- 25579538
TI  - Lapatinib plus trastuzumab in pretreated human epidermal growth factor receptor 2
      positive metastatic breast cancer.
AB  - BACKGROUND: Dual human epidermal growth factor receptor 2 (HER2) blockade has
      been preclinically and clinically assessed in HER2-overexpressing metastatic
      breast cancer (mBC) with encouraging results. PATIENTS AND METHODS: This is a
      descriptive retrospective study of trastuzumab plus lapatinib activity in
      patients with HER2-overexpressing mBC from two centers. The primary endpoints
      were to assess objective response rate (ORR) and toxicity. The secondary
      endpoints were to assess progression-free survival (PFS) and overall survival.
      RESULTS: A total of 23 HER2-positive mBC patients previously treated with
      trastuzumab received a trastuzumab plus lapatinib based therapy. Chemotherapy
      (CT) was added to the dual HER2 blockade treatment in 13 patients (56%), whereas
      hormonotherapy (HT) was added in 8 patients (35%) and 2 patients (9%) received
      lapatinib plus trastuzumab without any other agent. ORR was 22% (5/23) and 39%
      (9/23) of patients had stable disease. PFS in the overall population was 4
      months. PFS in patients with CT was 5 months, whereas PFS in patients with HT was
      2 months. Grade>=3 adverse events were diarrhea (26%) and hand-and-foot syndrome
      (9%). CONCLUSIONS: These findings suggest that dual HER2 blockade in combination
      with CT is feasible in pretreated HER2-positive mBC patients.

PMID- 25579539
TI  - Study on application of ultrasound microbubbles in the diagnosis of buccal
      carcinoma and metastatic cervical lymph nodes in mice.
AB  - BACKGROUND: This project's aim was to explore the enhancing effect of contrast
      media on primary cancer and cervical metastatic lymph nodes of cheek carcinoma by
      local injection. MATERIALS AND METHODS: Lymphatic metastasis cheek carcinoma mice
      models were established, then self-made contrast media was administered into the
      primary cheek carcinoma and harmonic mode imaging was performed to observe the
      enhancement of primary lesions and cervical metastatic lymph nodes. RESULTS: The
      echo intensity (EI) was compared. The detection rate of metastatic lymph nodes
      and inflammatory lymph nodes was 61% (17/28) and 50% (6/12) before contrast
      enhanced ultrasound (CEUS) imaging and 82% (23/28) and 75% (9/12) after CEUS
      imaging. After CEUS imaging, the EI of primary cancer and cervical metastatic
      lymph nodes was significantly increased, (P<0.01). CONCLUSION: After injection of
      self-made contrast media via the primary lesion, it can enter the lymph duct and
      obviously enhance the effect of ultrasonography on cervical metastatic lymph
      nodes of cheek carcinoma.

PMID- 25579540
TI  - Sanazole directed targeting of silver nanoparticle drug complex to tumor mass: a
      preclinical investigation in murine model.
AB  - AIM OF STUDY: To explore sanazole (AK) directed targeting of the antineoplastic
      drug doxorubicin (DOX) complexed with silver nanoparticles (SNs) to tumor growth
      in a murine model. MATERIALS AND METHODS: Sanazole (AK) and DOX were complexed
      with SNs, individually and in combination to obtain SN-AK, SN-DOX, and SN-AK-DOX.
      Solid tumors were developed on hind limbs of Swiss albino mice by transplanting
      Dalton's lymphoma ascitess (DLAs) tumor cells. Induction of cytotoxicity and
      apoptosis in the DLA cells by AK and DOX complexed with SN, individually and in
      combination, were examined under in vitro conditions by incubating the cells with
      them. SN, AK, DOX, SN-AK, SN-DOX, AK-DOX, and SN-AK-DOX were administered orally
      to the tumor bearing mice and the therapeutic efficacy of AK-directed targeting
      of SN-DOX complexes to achieve tumor control was monitored. RESULTS: Under in
      vitro conditions, SN, AK, DOX, SN-AK, SN-DOX, AK-DOX, and SN-AK-DOX induced
      cytotoxicity and apoptosis in DLA cells to varying extents. The SN-AK-DOX complex
      showed higher level of cytotoxicity and apoptosis-induction in DLA cells.
      Similarly, administration of SN, AK, DOX, SN-AK, SN-DOX, AK-DOX, and SN-AK-DOX
      resulted in significant reduction in tumor volume and delay in tumor growth. The
      animals treated with SN-AK-DOX had the highest reduction in tumor volume and
      tumor growth. In fact, the tumor was almost absent in the animals of this group
      after the treatment. CONCLUSION: The SN complex of sanazole and doxorubicin
      together (SN-AK-DOX) has high anticancer activity under in vivo conditions and
      has great potential in tumor therapy.

PMID- 25579541
TI  - Esophageal suspension method in scavenging peripheral lymph nodes of the left
      recurrent laryngeal nerve in thoracic esophageal carcinoma through semi-prone
      position thoracoscopy.
AB  - OBJECTIVE: Many Chinese doctors have performed microinvasive esophageal cancer
      resection in the semi-prone position. However, few reports have focused on high
      quality methods of scavenging the peripheral lymph nodes (PLNs) of the left
      recurrent laryngeal nerve (RLN). MATERIALS AND METHODS: Retrospective analysis
      was performed on 145 cases of microinvasive esophageal cancer resection in the
      semi-prone position. Among which, 75 cases underwent complete freeing of the
      thoracic esophagus and subsequent scavenging of the PLNs of the left RLN from
      April 2011 to April 2012 (Group A). In the other 70 cases, the incompletely freed
      upper thoracic esophagus was suspended, and the PLNs of the left RLN were
      scavenged from May 2012 to April 2013 (Group B). RESULTS: The average number of
      scavenged PLNs of the left RLN in Groups A and B was 4.6+/-2.9 and 5.2+/-3.0
      pieces, respectively (P=0.799). The total scavenged PLNs of the left RLN in
      Groups A and B were 344 and 357 pieces, respectively. Among which, the broken
      lymph nodes were 109 and 66 pieces, respectively (P<0.0001). The postoperative
      hoarseness rate in Groups A and B was respectively 12.0% and 2.8% (P=0.038).
      CONCLUSIONS: Dissection of the left RLN can be easily performed after esophageal
      suspension, thus ensuring the quality of PLN scavenging.

PMID- 25579542
TI  - Carvedilol suppresses migration and invasion of malignant breast cells by
      inactivating Src involving cAMP/PKA and PKCdelta signaling pathway.
AB  - CONTEXT: Carvedilol (CAR) can inhibit cell growth and induce cell apoptosis in
      breast cancer in vitro. But it is still not known whether CAR affects the
      migration and invasion of breast cancer cells. AIMS: To investigate the effects
      of CAR on migration and invasion of breast cancer cells and its corresponding
      signal pathways. SETTINGS AND DESIGN: Firstly, the invasive potential of breast
      cancer cells were investigated after incubation with CAR and/or norepinephrine
      (NE). If the invasive potential of breast cancer cells were inhibited by CAR,
      then the signal pathways related to migration and invasion were detected, such as
      Src, cyclic adenosine monohposphate (cAMP)/protein kinase A (PKA), etc. SUBJECTS
      AND METHODS: Membrane invasion culture system (MICS) chamber was used to measure
      the invasive and migratory potential of breast cancer cells. Western blot
      analysis and small interfering RNA (siRNA) transfection experiment were employed
      to determine the signal pathway adopted by CAR in suppressing migration and
      invasion of MDA-MB-231 and MCF-7 cells. cAMP-Glo and PKCdelta kinase activity
      assay kit were used to measure cAMP and PKCdelta activity, respectively,
      according to the manufacturer's instructions. STATISTICAL ANALYSIS USED:
      Statistical differences between the mean values of control and experimental
      groups were determined using two-tailed, unpaired Student's t-tests. RESULTS: CAR
      significantly decreased the potential of migration and invasion of breast cancer
      cells. CAR inhibited Src activation in MDA-MB-231 and MCF-7 cells through
      blocking beta or alpha adrenergic receptor (ADR), respectively. Furthermore, CAR
      suppressed the Src activation through different signaling pathways. Under
      treatment of CAR, cAMP/PKA-Src pathway was inhibited in MDA-MB-231 cells; but in
      MCF-7 cells, CAR mainly inhibited the PKCdelta-Src pathway. CONCLUSIONS: CAR was
      an anti-metastatic agent, which targets Src involving cAMP/PKA or PKCdelta
      pathway in malignant breast cells.

PMID- 25579543
TI  - Changes in lymphocytes' telomerase activity by 4-1BB costimulation.
AB  - AIM: Lymphocytes are exceptional among somatic cells as these cells can induce
      telomerase enzyme after antigen stimulation to compensate chromosomal loss during
      rapid cell division. Activation of telomerase in lymphocytes needs CD28 signal,
      which simultaneously costimulates T cells during activation. 4-1BB of tumor
      necrosis factor superfamily also has been shown to costimulate T cells. Herein,
      we investigated changes in telomerase activity of lymphocytes during longitudinal
      cultures when T cells costimulated by CD80 or 4-1BB ligand or both molecules in
      conjunction with anti-CD3 stimulation. MATERIALS AND METHODS: Artificial antigen
      presenting cells (aAPCs) were produced by transduction of CD80, 4-1BB ligand or
      green fluorescent protein genes into A549 carcinoma cells using recombinant
      adenoviral vectors. Peripheral blood mononuclear cells were stimulated with anti
      CD3 and co-cultured with the aAPCs. Cellular growth, expression of telomerase and
      production of interferon gamma (IFN-gamma) were assessed at different time points
      and followed up to day 35. RESULTS: 4-1BBL provided effective costimulation for
      lymphocytes' activation, cytokine production or long-lasting growth where its
      effects exceeded over CD80 after the first week. 4-1BBL also promoted the
      telomerase activity and more importantly was able to re-induce the enzyme in the
      cells that stopped to grow with CD80 costimulation. Although combination of CD80
      and 4-1BBL has additional effect on cellular growth or initial telomerase
      activity, it could not support telomerase activity in later time points.
      CONCLUSION: Our results underscored unique features of 4-1BB over CD28 for
      prolonged support of lymphocytes' costimulation, which can be recruited for in
      vitro or ex vivo propagation of T cells for cancer immunotherapy purposes.

PMID- 25579544
TI  - The comparison of antimutagenicity and anticancer activities of Echinophora
      platyloba DC on acute promyelocytic leukemia cancer cells.
AB  - BACKGROUND: Cancer is one of the main causes of mortality in the world which is
      created by the effect of enviromental physico-chemical mutagen and carcinogen
      agents. In the last years, many studies have been performed on the anticancer
      effects of flavonoids. Echinophora platyloba DC plant (Khousharizeh) is one of
      the indigenous medicinal plants which is used as a food seasoning and medicine in
      Iran. MATERIALS AND METHODS: The extract was evaluated in terms of
      antimutagenicity properties by a standard reverse mutation assay (Ames Test).
      This was performed with histidine auxotroph strain of Salmonella typhimurium
      (TA100). Thus, it requires histidine from a foreign supply to ensure its growth.
      The afore mentioned strain gives rise to reverted colonies when expose to
      carcinogen substance (Sodium Azide). The other objective of this study was to
      examine the in vitro cytotoxic activity of cell death of crude methanolic
      extracts prepared from Echinophora platyloba on Acute Promyelocytic Leukemia cell
      line (NB4). Cytotoxicity and viability of methanolic extract was assessed by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye
      exclusion assay. RESULTS: In Ames test the extract prevented the reverted
      mutations and the hindrance percent was 93.4% in antimutagenicity test. Data
      obtained from this assay indicated that the extract significantly reduced the
      viability of NB4 cells and inhibited cell growth in a dose dependent manner.
      CONCLUSION: This study demonstrates the antimutagenicity effect of Echinophora
      Platyloba and suggests that it has a potential as an anticancer agent.

PMID- 25579545
TI  - Absence of p53 gene mutations in mice colon pre-cancerous stage induced by o
      nitrotoluene.
AB  - p53 gene is one of the most frequently mutated genes found in the human colonic
      tumors. Mice have been used as an experimental model to study the pathogenesis of
      colon cancer in humans. The alterations in cancer genes and proteins found in the
      mouse large intestinal tumors included mutations which are hallmarks of human
      colon cancer, probably contributed to the pathogenesis of the large intestinal
      carcinomas in mice following o-nitrotoluene (o-nt) exposure. AIM OF STUDY:
      Detection of p53 gene mutations in colon precancerous stage. MATERIALS AND
      METHODS: In this study, mice colon precancerous stage induced by o-nt were
      examined for the presence of point mutations in highly conserved coding region
      (exons 5-8) and outside it (exons 10, 11) using a single-strand conformation
      polymorphism assay (SSCP). RESULTS: SSCP analysis showed no differences in
      banding patterns between the normal negative control group and o-nt-induced
      precancerous stage in mice colon. CONCLUSION: The results from the present study
      indicate that point mutations in the p53 gene, in the coding region (exons 5-8)
      and outside it (exons 10, 11), are not involved in the development of the colon
      precancerous stage induced by o-nt in mice.

PMID- 25579546
TI  - Bioinformatics analysis of aggressive behavior of breast cancer via an integrated
      gene regulatory network.
AB  - BACKGROUND: Breast cancer is one of the most frequently diagnosed cancers in
      women. Though death from this disease is mainly caused by the metastases of the
      aggressive cancer cells, few studies have expounded the aggressive behavior of
      breast cancer. MATERIALS AND METHODS: We downloaded the gene expression profiles
      of GSE40057, including four aggressive and six less-aggressive breast cancer cell
      lines, from Gene Expression Omnibus and identified the differentially expressed
      genes (DEGs) between the aggressive and less-aggressive samples. An integrated
      gene regulatory network was built including DEGs, microRNAs (miRNAs), and
      transcription factors. Then, motifs and modules of the network were identified.
      Modules were further analyzed at a functional level using Gene Ontology (GO) and
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to study the aggressive
      behavior of breast cancer. RESULTS: A total of 764 DEGs were found and two
      modules were filtered from the integrated gene regulatory network. Totally two
      motifs and modules for DEGs were identified. Significant GO terms associated with
      cell proliferation and hormone stimulus of the modules were found and the target
      genes identified were  CAV1, CD44, and TGFbetaR2. The KEGG pathway analysis
      discovered that CAV1 and FN1 were significantly enriched in focal adhesion,
      extracellular matrix (ECM)-receptor interaction, and pathways in cancer.
      CONCLUSION: Aggressive behavior of breast cancer was proved to be related to cell
      proliferation and hormone stimulus. Genes such as CAV1, CD44, TGFbetaR2, and FN1
      might be potential targets to diagnose the aggressive behavior of breast cancer
      cells.

PMID- 25579547
TI  - Changes of serum albumin level and systemic inflammatory response in inoperable
      non-small cell lung cancer patients after chemotherapy.
AB  - AIM: Hypoalbuminemia and systemic inflammatory response (SIR) parameters are a
      key role in the prognosis of cancer patients. We aim to investigate the changes
      of serum albumin level and SIR after chemotherapy, in patients with inoperable
      non-small cell lung cancer (NSCLC). The hypothesis is that improved serum albumin
      level may be beneficial to the SIR parameters and will reduce chemotherapy
      induced toxicity. PATIENTS AND METHODS: Forty-nine stage III b or stage IV
      inoperable NSCLC patients were divided into two groups, depending on whether
      albumin administration was given before chemotherapy. The Karnofsky performance
      score (KPS), nutritional status including body mass index (BMI), and serum
      albumin level were evaluated. SIR was evaluated by investigating the changes of
      the C-reactive protein (CRP), calculating the neutrophil lymphocyte ratio (NLR),
      and the platelet lymphocyte ratio (PLR), before and after chemotherapy. The
      chemotherapy-induced toxicity was also evaluated. RESULTS: In the group of
      patients without albumin administration before chemotherapy, the serum albumin
      level was significantly decreased (P<0.05) and the CRP level was significantly
      increased than before (P<0.05). Significant correlations were noted between
      hypoalbuminemia and CRP increase (r=0.533 P<0.05), between hypoalbuminemia and
      NLR>=5 (r=0.574 P<0.01) after chemotherapy. Patients with hypoalbuminemia
      developed more severe chemotherapy-induced toxicity symptoms. In the group of
      patients with albumin administration before chemotherapy, there was no
      significant difference in serum albumin level before and after chemotherapy
      (P>0.05), even though the patients may have been malnourished or diagnosed with
      pleural effusions. There were no significant changes in the SIR parameters.
      CONCLUSION: Early assessment of the serum albumin level in patients with
      inoperable NSCLC and their improvement in the serum albumin level may suggest
      that there are beneficial effects after chemotherapy.

PMID- 25579548
TI  - Cyclo-oxygenase-2 expression in oral squamous cell carcinoma.
AB  - BACKGROUND: Many evidences showed that cyclooxygenase-2 (COX-2), an enzyme that
      catalyzes the synthesis of prostaglandins, has an important role in
      carcinogenesis. It has been observed in experimental models that selective COX-2
      inhibitors suppress the formation of tumors including tongue carcinoma. The aim
      of this study was to investigate the immunohistochemical expression of COX-2 in
      oral squamous cell carcinoma (OSCC) compared to normal oral mucosa and oral
      dysplasia. MATERIALS AND METHODS: A total of 60 paraffined blocks (20 cases of
      OSCC, 20 cases of oral epithelial dysplasia and 20 cases of normal oral mucosa
      were included in this study and immunohistochemical staining was done for COX-2
      expression. From each sample, 5 high power fields were assessed to determine the
      percentage of stained cells and staining intensity. Immunoreactivity was obtained
      by multiplying the above two cases. Data were analyzed with using the Kruskal
      Wallis test ANOVA, Mann-Whitney test and least significant difference and P<0.05
      was declared as significant. RESULTS: High level of COX-2 expression was found in
      OSCC and dysplasia compared to normal mucosa. Furthermore, a positive correlation
      was found between COX-2 expression and severity of dysplasia. However, no
      significant difference between low grade and high grade tumors was found.
      CONCLUSION: The result of the present study supports from the role of COX-2 in
      carcinogenesis and progression of premalignant lesion to malignancy.

PMID- 25579549
TI  - Investigation on immune function and chest drainage in patients with thoracic
      malignancies using the streptococcal agent Sapylin.
AB  - PURPOSE: To investigate the influence of Sapylin used during the operation on
      immune function and chest drainage in patients with thoracic malignancies in
      early postoperative period. PATIENTS AND METHODS: Seventy-one patients with
      thoracic malignancies including lung cancer and esophageal carcinoma who
      underwent tumor resection were divided into two groups, 36 cases of observation
      group and 35 cases of control group. In observation group, Sapylin were locally
      laid in operation field during the operation. The control group was not given
      Sapylin. Drainage volume of chest cavity after operation, and the levels of CD4,
      CD8, CD4/CD8 and natural killer (NK) cell were recorded. RESULTS: The level of
      CD4+, CD4+/CD8+ and NK cell in observation group were higher than that in control
      group (P<0.05) wholly in early postoperative period. Drainage volume of chest
      cavity in observation group was less than that in control group postoperatively,
      1160.2+/-437.2 ml vs. 1363.3+/-472.9 ml, but the change in two groups had no
      significance statistically (P=0.064). CONCLUSIONS: The local application of
      Sapylin during operation can improve immunity of patients with thoracic
      malignancies significantly and decrease the drainage volume of chest cavity
      probably in early postoperative period. So it is worthy of popularizing in
      clinical practice.

PMID- 25579550
TI  - Potent chemopreventive effect of mangiferin on lung carcinogenesis in
      experimental Swiss albino mice.
AB  - AIM OF THE STUDY: In the present study the effects of mangiferin were tested
      against lung cancer-bearing mice in both the pre-initiation and post-initiation
      periods. MATERIALS AND METHODS: Healthy male Swiss albino mice (6-8 weeks old)
      were used throughout the study. The animals were treated with mangiferin (100
      mg/kg body weight dissolved in corn oil) two weeks before (pre-initiation) and
      the twelfth week after (post-initiation) the establishment of B (a) P (50 mg/kg
      body weight)-induced lung carcinoma. RESULTS: The body weight decreased and the
      lung weight and levels of xenobiotic and liver marker enzymes markedly increased
      in the carcinogen-administered animals; and mangiferin treatment brought the
      values of these parameters back to the near-normal ones. The activities of
      lysosomal enzymes in the animals with B (a) P-induced experimental lung
      carcinogenesis were also assessed. In these animals there was an increase in the
      activities of lysosomal enzymes such as acidphosphatase, beta-glucuronidase, N
      acetyl glucosaminidase, and beta-galactosidase. CONCLUSION: Supplementation with
      mangiferin attenuated all these alterations, thus indicating its anticancer
      effect. Overall, the above data showed that the anticancer effect of mangiferin
      as a chemopreventive agent was pronounced.

PMID- 25579551
TI  - Effect of melatonin on antioxidant status and circadian activity rhythm during
      hepatocarcinogenesis in mice.
AB  - AIM: Alteration of circadian systems can cause cancer and affects its development
      and response to therapeutics. The present study investigates whether cancer can
      disrupt circadian locomotor rhythms and evaluated the influence of melatonin
      (MLT) and oxaliplatin on the levels of antioxidants and circadian locomotor
      activity rhythms in N-nitrosodiethylamine (NDEA)-induced liver tumor in Indian
      field mouse (Mus booduga). MATERIALS AND METHODS: Effects of NDEA, NDEA, and MLT,
      as well as NDEA and oxaliplatin, on levels of mice liver marker enzymes and
      antioxidants and their circadian locomotor activity rhythm were assessed.
      RESULTS: Treatment of mice with NDEA caused significant alteration of their liver
      marker enzymes [aspartate transaminase and alanine transaminase; P<0.05 Duncan's
      multiple range test (DMRT) test] antioxidant levels (superoxide dismutase,
      catalase, glutathione peroxidase, glutathione-S-transferase; P<0.05, DMRT test]
      and circadian locomotor activity rhythm, which were abrogated when the animals
      were also given MLT or the anticancer drug, oxaliplatin. CONCLUSION: Our study
      demonstrated that the circadian clock was disturbed by hepatocarcinogenesis and
      the effects could be reversed by the chronobiotic, MLT.

PMID- 25579553
TI  - Prognostic significance of metastasis associated in colon cancer 1 (MACC1)
      expression in patients with gallbladder cancer.
AB  - BACKGROUND: The clinical significance of metastasis associated in colon cancer 1
      (MACC1), in human gallbladder cancer, is not yet established. This study was
      performed to assess the expression of MACC1 in benign and malignant gallbladder
      lesions, and to assess its clinicopathological significance. MATERIALS AND
      METHODS: Tissue samples from resected gallbladder cancer (n=70) and
      cholelithiasis (n=70) were evaluated for MACC1 expression by immunohistochemical
      staining. Their expression was correlated with different clinicopathological
      parameters. RESULTS: Cytoplasmic MACC1 expression was significantly higher
      (58.6%) in gallbladder cancer than in chronic cholecystitis (27.1%, P<0.001).
      High MACC1 levels were associated with lymph node metastasis (P<0.05), tumor node
      metastasis (TNM) stage (P<0.01), and perineural invasion (P<0.01), but not with
      sex, age, history of gallstones or histological grade (P>0.05). The univariate
      Kaplan-Meier analysis showed that a positive MACC1 expression was associated with
      decreased overall survival (P<0.001). The multivariate Cox regression analysis
      showed that MACC1 expression and the histopathological subtypes were independent
      risk factors for disease-free survival. CONCLUSION: The expression of MACC1 might
      be closely related to carcinogenesis, clinical biological behaviors, and
      prognosis of gallbladder adenocarcinoma.

PMID- 25579552
TI  - In vitro anticancer effects of insect tea in TCA8113 cells.
AB  - BACKGROUND: Insect tea is widely used a traditional drink or traditional Chinese
      medicine in China. This study was conducted with an aim to determine the in vitro
      anticancer effect of Insect tea in cancer cells. MATERIALS AND METHODS: The
      anticancer effects of Insect tea were evaluated in human tongue carcinoma TCA8113
      cells using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT)
      assay, flow cytometry analysis, nuclear staining with 4,6-diamidino-2
      phenylindole (DAPI), reverse transcription-polymerase chain reaction (RT-PCR)
      analysis, and western bolt assay. RESULTS: At 200 MUg/mL, Insect tea inhibited
      the growth of TCA8113 cells by 80.7%, which was higher than the inhibition caused
      by 100 MUg/mL Insect tea but lower than that of 200 MUg/mL green tea. Compared to
      the control cancer cells, Insect tea significantly (P<0.05) induced apoptosis as
      determined by DAPI staining and flow cytometry analysis results. Insect tea
      significantly induced apoptosis in cancer cells by upregulating BAX, CASP3, CASP9
      and downregulating BCL2. Genes encoding nuclear factor kappa-light-chain-enhancer
      of activated B cells (NF-kappaB), inducible nitric oxide synthase (iNOS), and
      cyclooxygenase-2 (COX-2) were significantly downregulated by Insect tea,
      demonstrating its anti-inflammatory properties. Insect tea also exerted a great
      anti-metastasis effect on cancer cells as demonstrated by decreased expression of
      matrix metalloproteinase (MMP) genes and increased expression of tissue
      inhibitors of metalloproteinases (TIMPs). CONCLUSION: The results showed that
      Insect tea has good in vitro anticancer effects in TCA8113 cells, like green tea.

PMID- 25579554
TI  - A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid
      on 5637 (bladder cancer) and 4T1 (Breast cancer) cell lines.
AB  - CONTEXT: Anticancer properties of artemisinin and its derivatives have been shown
      in many experiments. AIMS: Addition of butyric acid, miconazole, and iron to this
      traditional drug has been done in order to enhance its anticancer potency.
      MATERIALS AND METHODS: Cell lines 5637 and 4T1, were cultivated and classified
      into 13 groups of three each. Different doses of artemisinin with constant doses
      of iron, miconazole and butyric acid, were added to the cultures. At the end of
      exposure pathological and enzymatic studies were performed. RESULTS: In four
      groups treated with different doses of artemisinin and iron, dose-dependent
      changes were observed. These changes included apoptosis and necrosis with
      dominance of apoptosis. The supernatant lactate dehydrogenase (LDH) level was
      increased in a dose-dependent manner, but there was no significant increase in
      the cell fraction of malonyldialdehyde (MDA) or LDH. In four other groups, which
      received miconazole, butyric acid and iron in addition to different doses of
      artemisinin, necrosis was more prominent than apoptosis, and the MDA level did
      not show any significant change, but LDH was increased. The groups treated with
      miconazole showed identical changes, with less severity compared to combination
      therapy groups. In butyric acid-treated groups, the only detectable changes were,
      mild cell swelling, few apoptosis, and rare necrosis. CONCLUSIONS: A combination
      therapy with artemisinin can be more effective against cancer cells than
      monotherapy with that. Butyric acid was not effective on cancer cells. Miconazole
      deviated the nature of cell death from apoptosis to necrosis and it must be used
      under caution.

PMID- 25579555
TI  - Downregulation of beta-catenin decreases the tumorigenicity, but promotes
      epithelial-mesenchymal transition in breast cancer cells.
AB  - BACKGROUND: Wnt/beta-catenin signaling pathway plays a key role in human breast
      cancer progression. In this study, we down regulated beta-catenin expression in
      human breast cancer MDA-MB-231 cells and investigated the effect of beta-catenin
      knockdown on the cell biological characteristics. MATERIALS AND METHODS: The
      recombinant plasmids of pSUPER-enhancement green fluorescent protein 1 (EGFP1)
      scrabble-beta-catenin-short hairpin ribonucleic acid (shRNA) and pSUPER-EGFP1
      beta-catenin-shRNA-1 were transfected into MDA-MB-231 cells, respectively, and
      the stably transfected cells were isolated from G418 selected clones. The beta
      catenin gene silenced efficiency was measured by quantitative reverse
      transcriptase polymerase chain reaction (QRT-PCR) and Western blot. The
      biological characteristics of MDA-MB-231 cells with down regulated beta-catenin
      were evaluated by analyzing cell proliferation, clonogenicity, cell mobility and
      tumorigenicity. The expression of E-cadherin and Vimentin was concurrently
      detected by QRT-PCR. RESULTS: The beta-catenin-shRNA-1 stably transfected MDA-MB
      231 cells significantly decreased beta-catenin expression, cell proliferation,
      clonogenicity, and tumorigenicity in Balb/c nude mice compared with the MDA-MB
      231 cells transfected with pSUPER-EGFP1-scrabble-beta-catenin-shRNA.
      Interestingly, knockdown of beta-catenin led to the reduction of epithelial E
      cadherin expression, the increase of cell mobility and mesenchymal vimentin
      expression in MDA-MB-231 cells, indicating an epithelial to mesenchymal
      transition. CONCLUSION: Knockdown of beta-catenin expression in human breast
      cancer MDA-MB-231 cells inhibits cell tumorigenicity in mice, but promotes cell
      epithelial-mesenchymal transition.

PMID- 25579556
TI  - Antitumor activity of Pogostemon benghalensis Linn. on ehrlich ascites carcinoma
      tumor bearing mice.
AB  - BACKGROUND: Pogostemon benghalensis has been used traditionally as anticancer in
      India. AIM OF THE STUDY: The present study was undertaken to investigate the
      antitumor activity of hydroethanolic extract of P. benghalensis (HEEPB) and
      aqueous extract of P. benghalensis (AEPB) on ehrlich ascites carcinoma (EAC)
      tumor bearing mice. MATERIALS AND METHODS: For antitumor effect, treatments with
      HEEPB and AEPB at doses of 250 mg/kg and 500 mg/kg/day orally were started after
      24 h of intraperitoneal inoculation of EAC cells. After the treatment period,
      median survival time (MST), hematological parameters and solid tumor volume were
      used to evaluate antitumor activity of the extracts. RESULTS: Both, HEEPB and
      AEPB, have increased MST (P<0.05), reduced solid tumor volume (P<0.05) and
      normalized hematological parameters (P<0.05) significantly. CONCLUSION: As HEEPB
      and AEPB were effective in reducing the severity of morphological and biochemical
      parameters induced by EAC cells, this study justifies the traditional use of this
      plant in cancer.

PMID- 25579557
TI  - Comparison of clinicopathological parameters with FoxM1 expression in renal cell
      carcinoma.
AB  - AIM: To investigate the relationships between expression of forkhead box M1
      (FoxM1) and clinicopathologic parameters and Ki-67 expression in patients with
      renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 67 cases of RCC
      including 47 cases of clear cell RCC (ccRCC), five cases of papillary RCC (pRCC),
      eight cases of chromophobe RCC (chRCC), four cases of unclassified (with
      sarcomatoid pattern) RCC (sRCC), and three cases of multilocular RCC (mRCC) were
      included to this study. The expression of FoxM1 protein was assessed in 67
      samples of RCC using immunohistochemical methods and the relationship between the
      expression levels of FoxM1 with clinicopathological characteristics and Ki-67
      expression of RCC patients. For statistical analysis, the cases were grouped into
      the ccRCC and non-ccRCC group. RESULTS: Immunohistochemistry analyses showed that
      FoxM1 protein expression in 47 ccRCC samples was significantly correlated with
      tumor size, stage, nuclear grade, capsule invasion, perinephric fat invasion, and
      Ki-67 expression (P<0.05 for all); whereas, no correlations were found in
      patients' age, gender, and lymph node metastasis (P>0.05 for all). In 20 non
      ccRCC; overexpression of FoxM1 was strongly associated with tumor size (P<0.05).
      There was no relationship between FoxM1 expression with other clinicopathological
      parameters and Ki-67 expression in non-ccRCC (P>0.05 for all). CONCLUSION: This
      study showed that FoxM1 have a progressive oncogenic role in ccRRC. Our results
      suggested that higher expression of FoxM1 in tumor tissues predicts a locally
      aggressive behavior and poor outcome of patients with ccRCC, but not in patient
      with non-ccRCC.

PMID- 25579558
TI  - Effects of ameloblastoma-associated fibroblasts on the proliferation and invasion
      of tumor cells.
AB  - CONTEXT: Ameloblastoma is the most common odontogenic tumor, however, the
      molecular pathology, especially the role of the tumor stroma, is still unclear.
      AIMS: To investigate the effects of the ameloblatoma-associated fibroblast (AAFs)
      on the proliferation and invasion of tumor cells. SETTINGS AND DESIGN: Cell
      culture, ELISA, proliferation and invasion assays. METHODS AND MATERIAL: The
      cocultivations and three-dimensional organotypic cultures of the AAFs and the
      tumor cells were performed. The gingival fibroblasts (GFs) were used as the
      control. The levels of TGF-beta and HGF in the conditioned media were analyzed
      using ELISA technique. The MTT proliferation assays and Boyden chamber
      chemoinvasion assays were also performed. STATISTICAL ANALYSIS USED: ANOVA.
      RESULTS: Both AAFs and GFs stimulated tumor cell growth. The TGF-beta level in
      the AAF group was more than those of GF group, whereas the HGF levels were not
      different. The AAF conditioned media also stimulated tumor cell proliferation and
      invasion more than the GF conditioned media. However, no difference in the
      thickness and morphology between the AAF and GF groups could be demonstrated in
      the organotypic models. CONCLUSIONS: Both AAFs and GFs support the proliferation
      of the tumor cells in cocultivation experiment and three-dimensional organotypic
      cultures. However, the AAFs have a tendency to stimulate the proliferation and
      induce the invasion more than GFs. Increased TGF-beta levels in the AAF condition
      media suggested the possible role of this growth factor in the ameloblastoma
      biology.

PMID- 25579559
TI  - Analysis of gingival biopsies in the Gujarati population: a retrospective study.
AB  - BACKGROUND: Biopsy is an important diagnostic tool used in the diagnosis of
      lesions ranging from simple non-neoplastic, tumor-like lesions to malignancies,
      and is often the only way to diagnose oral lesions and diseases. The gingiva is
      the most common site for some kind of irritation or low-grade injury, resulting
      in localized overgrowths that are considered to be reactive and non-neoplastic
      lesions. This aim of this study is to analyze the frequency and distribution of
      gingival lesions in the Gujarati population. MATERIALS AND METHODS: In this
      retrospective study, gingival biopsies submitted for a period of five years were
      included. Microscopic slides of all the cases were reviewed by two observers for
      confirmation of the diagnosis. RESULTS: Among the 106 cases of gingival biopsies,
      the most frequent category of lesions encountered was the non-neoplastic
      category, which accounted for 73.58% of the cases. Both benign and malignant
      neoplasms constituted 26.42% of the cases. Among the non-neoplastic lesions,
      Pyogenic granuloma was the most frequent lesion (38.46%), followed by fibrous
      hyperplasia (20.51%), inflammatory hyperplasia (19.23%), and Epulis (8.97%).
      Neoplasms accounted for 26.42% of the gingival biopsies (92.85% benign and 7.15%
      malignant). Among the benign neoplastic lesions, Fibroma (30.76%) and Fibrolipoma
      (26.92%) were the most frequent, followed by peripheral ossifying fibroma
      (23.08%) and peripheral giant cell granuloma (11%). CONCLUSION: It is difficult
      to compare studies carried out in various countries due to differences in
      people's attitudes toward oral health and the accessibility of various population
      groups to biopsy services. Nevertheless, this study has provided some information
      about the frequency and distribution of biopsied gingival lesions in the Gujarati
      population over a period of five years.

PMID- 25579560
TI  - Radiation recall phenomenon presenting as myositis triggered by carboplatin plus
      paclitaxel and related literature review.
AB  - While most case reports to date are radiation recall dermatitis, radiation recall
      myositis, which is a distinct form of radiation recall phenomenon caused by
      carboplatin plus paclitaxel, has not been reported. We treated a 57-year-old
      female patient who suffered from recurrent cervical cancer. When the patient
      developed a new left sacral metastasis, salvage radiotherapy (total dose 60 Gy)
      was administered. Four weeks later, chemotherapy using carboplatin plus
      paclitaxel was initiated. Four months after chemotherapy, the patient complained
      of severe pain in her left buttock. On magnetic resonance imaging (MRI),
      edematous changes and increased signal densities of left gluteus maximus and
      medius muscles were noted suggesting myositis. The border of the high signal
      intensity territory of the muscles was sharp and clearly corresponded with the
      recent irradiation field. We concluded that the patient had radiation recall
      myositis triggered by paclitaxel-carboplatin. Symptoms were controlled by
      analgesics, and there was no recurrence. 

PMID- 25579561
TI  - Large oculomotor nerve schwannoma--rare entity: a case report with review of
      literature.
AB  - Schwannomas commonly arise from peripheral nerves. Intracranial schwannomas are
      comparatively rare and are seen commonly as vestibular tumors. Oculomotor nerve
      schwannomas are extremely rare tumors, these are usually symptomatic. A 29 year
      aged male presented with diplopia and blurring of vision in left eye and found to
      have an extra-axial lesion at left cavernous sinus involving oculomotor nerve.
      The excised tumor showed classic morphology of a schwannoma. Postoperatively
      patient developed complete oculomotor nerve palsy. The tumor recurred after 2
      years. It was re-excised followed by radiotherapy. 

PMID- 25579562
TI  - Sphenoidal esthesioneuroblastoma treated with sequential chemo radiotherapy: a
      case report and review of the literature.
AB  - Esthesioneuroblastoma (ENB)-also known as olfactory neuroblastoma-originates
      primarily from the olfactory epithelium in the roof of the nasal cavity. We
      present here the 7th reported case of ENB arising from the sphenoidal sinus. We
      undertook a review of the case notes from the time of initial presentation and
      literature review of this topic. A 55-year-old male presented with a 3-year
      history of unilateral progressive nasal obstruction, epistaxis, difficult nasal
      breathing, facial pain, frontal headache and blood-tinged discharge. Nasal
      examination revealed a glistening mass in right nasal cavity. Endoscopy-assisted
      transnasal excision was performed. Histologically, tumor was identified as small
      round cell tumor and confirmed by immunohistochemistry to be olfactory
      neuroblastoma (negative leucocyte common antigen, positive neurone specific
      enolase). Sphenoidal ENB is rare in the literature, and this presentation is the
      7th reported case; in addition, surgical treatment is very challenging, and non
      surgical treatment is used most commonly.

PMID- 25579563
TI  - Clear cell sarcoma of the kidney: a case report.
AB  - Clear cell sarcoma of the kidney is a rare malignant neoplasm of childhood, known
      for its aggressiveness, its tendency for recurrence, and to metastasize to bone.
      We report the observation of 8-month-old child presenting with a large abdominal
      mass. Clinically, it was diagnosed as Wilm's tumor, and left nephrectomy was
      done. Grossly, 10 cm*8 cm*3.5 cm globular, white, encapsulated, smooth mass
      uniformly involving the whole kidney was noted. Histologically, the tumor was
      diagnosed as clear cell sarcoma with renal vein showing presence of tumor embolus
      in lumen. The tumor was given stage-II (NWTS-5 protocol). Immunohistochemistry
      showed vimentin positive and cytokeratin negative tumor cells. The child is
      currently undergoing chemotherapy and has not yet shown any sign of bony
      metastasis.

PMID- 25579564
TI  - Newly diagnosed breast cancer in a patient receiving imatinib mesylate.
AB  - Imatinib mesylate is the standard treatment of chronic myeloid leukemia (CML).
      Despite imatinib is being used in the treatment of other malignancies as well,
      its potential role on de novo tumor growth is not known. Secondary malignancies
      are rarely seen in patients with CML and particularly in those receiving
      imatinib. Here, we present a CML patient taking imatinib therapy that was
      diagnosed to have breast cancer and received adjuvant chemo-and radiotherapy with
      imatinib. We tried to explain co-occurrence of these rare events by probable
      pathogenetic mechanisms. 

PMID- 25579565
TI  - Triple primary malignant neoplasms including breast, esophagus and base tongue in
      an elderly male: a case report.
AB  - Cases involving more than two primary malignant neoplasms are very rare. The
      present article reports a case of multiple primary malignant neoplasms including
      esophagus initially followed by right breast and later base of tongue in an
      elderly male patient, which is extremely a rare combination. 

PMID- 25579567
TI  - Mechanistics in drug design - experimental molecular biology vs. molecular
      modeling.

PMID- 25579566
TI  - Complete remission of hepatocellular carcinoma after transarterial
      Chemoembolization combined with brivanib.
AB  - Transarterial chemoembolization (TACE) has been the standard treatment modality
      in patients with intermediate stage hepatocellular carcinoma (HCC). Brivanib is
      an oral small molecular inhibitor of both vascular endothelial growth factor and
      fibroblast growth factor receptors. Herein, we reported that a 67-year-old
      patient with intermediate stage HCC achieved the complete remission after TACE
      combined with brivanib therapy. This finding potentially suggested the benefit of
      this combination therapy for HCC. 

PMID- 25579568
TI  - Tubulins - the target for anticancer therapy.
AB  - Tubulin has picked up great focus as a major target in drug discovery and
      consequently, tubulin inhibitors have pulling in a considerable attention as
      anticancer agents. Numerable naturally occurring agents have focused on tubulin
      system act as an imperative target of cancer chemotherapy. Substantial number of
      tubulin inhibitors has been discovered so far and these agents are classified as
      indicated by their interaction. They are colchicine site binder, vinca- alkaloid
      related drugs and those interacting with the Taxol binding site and functioning
      as stabilising agents. We review the recent advances in the advancement of
      tubulin interfering agents and will render the current trend in the improvement
      of tubulin inhibitors as anticancer agents. 

PMID- 25579569
TI  - Multiclass comparative virtual screening to identify novel Hsp90 inhibitors: a
      therapeutic breast cancer drug target.
AB  - Since the discovery of Hsp90, a decade ago, it has surfaced as a potential target
      in breast cancer therapy along with other cancers. In present study, we have
      selected seven established Hsp inhibitors viz., PU3, CCT-018159, CNF-2024, SNX
      5422, NVP (AUY-922), EGCG and IPI-504 used in the treatment of cancer.
      Considering these seven inhibitors as a parent compound, ligand based search was
      carried out with 90% similarity in Pubchem database (31 million compounds). All
      the similar molecules belonging to respective parent compound along with similar
      compound were subjected to virtual screening using MolDock and PLP algorithm
      aided molecular docking. Compounds with highest docking rerank scores were
      selected and filtered through Lipinski's drug-likeness filters and toxicity
      parameters. New candidate (Pubchem CID: 11363378) qualified to demonstrate
      considerable affinity towards Hsp90. The selected compound was further
      pharmcophorically incited for receptor- ligand interactions like H-bond,
      electrostatic, hydrophobic interactions etc. 

PMID- 25579570
TI  - Identification of high affinity bioactive Salbutamol conformer directed against
      mutated (Thr164Ile) beta 2 adrenergic receptor.
AB  - Salbutamol forms an important and widely administered beta2 agonist prescribed in
      the symptomatic treatment of bronchial asthma. Unfortunately, a subset of
      patients show refractoriness to it owing to ADRB2 gene variant (rs 1800888). The
      variant substitutes Thr to Ile at the position 164 in the beta2 adrenergic
      receptor leading to sub-optimal binding of agonists. The present study aims to
      associate the Salbutamol response with the variant and select the bioactive
      conformer of Sabutamol with optimal binding affinity against mutated receptor by
      in silico approaches. To assess bronchodilator response spirometry was performed
      before and 15 min after Salbutamol (200 mcg) inhalation. Responders to Salbutamol
      were categorized if percentage reversibility was greater than or equal to 12%,
      while those showing FEV1 reversibility less than 12% were classified as non
      responders. Among the 344 subjects screened, 238 were responders and 106 were non
      responders. The frequency of mutant allele "T" was significantly higher in case
      of non-responders (p < 0.05). In silico process involved generation of Salbutamol
      conformer ensembles supported by systematic search algorithm. 4369 conformers
      were generated of which only 1882 were considered bioactive conformers (threshold
      RMSD<=1 in reference to normalized structure of salbutamol). All the bioactive
      conformers were evaluated for the binding affinity against (Thr164 Ile) receptor
      through MolDock aided docking algorithm. One of the bioactive conformer (P.E. = 
      57.0038, RMSD = 0.6) demonstrated 1.54 folds greater affinity than the normal
      Salbutamol in the mutated receptor. The conformer identified in the present study
      may be put to pharmacodynamic and pharmacokinetic studies in future ahead.

PMID- 25579571
TI  - Insight into the binding mode between N-methyl pyrimidones and prototype foamy
      virus integrase-DNA complex by QM-polarized ligand docking and molecular dynamics
      simulations.
AB  - Human immunodeficiency virus type 1 (HIV-1) integrase (IN) is an essential enzyme
      in the viral replication cycle as it catalyzes the insertion of the reverse
      transcribed viral DNA into host chromosome. The structure of prototype foamy
      virus (PFV) IN has structural and functional homology with HIV-1 IN (no full
      length structure available). In this study, we have used PFV IN-DNA complex as a
      surrogate model for HIV-1 IN-DNA complex to investigate the binding modes of N
      methyl pyrimidones (NMPs) by QM-polarized ligand docking (QPLD), binding free
      energy calculations and molecular dynamics simulations. The O,O,O donor atom
      triad of NMPs show metal chelation with divalent Mg(2+) ions in the active site
      of PFV IN, in perfect agreement with the proposed mechanism of IN strand transfer
      inhibitors (INSTIs). The results also show that the benzyl group of compounds fit
      into a pocket to displace the 3'-terminal adenosine of viral DNA from the IN
      active site making it unavailable for the nucleophile to attack the target DNA in
      the strand transfer (ST) reaction. The halobenzyl moiety show hydrophobic
      interactions with conserved PFV IN Tyr212 and Pro214 residues, corresponding to
      HIV-1 IN Tyr143 and Pro145, respectively. Molecular dynamics (MD) simulations
      gave important insights into the structural and chemical basis involved in ST
      inhibition. Based on MD results, hydrogen bond with Tyr212, coordinate bonds with
      Mg(2+) ions, and hydrophobic interactions play an important role in the
      stabilization of compounds. Our results provide additional insight into the
      possible mechanism of action and binding mode of NMPs, and might have
      implications for rational design of specific HIV-1 INSTIs with improved affinity
      and selectivity.

PMID- 25579572
TI  - Design and virtual screening towards synthesis of novel substituted
      thiosemicarbozones as ribonuleotide reductase (RNR) inhibitors with improved
      cellular trafficking and anticancer activity.
AB  - Ribonucleotide reductase subunit R2 regulates catalytic action of the enzyme to
      provide DNA synthesis material via reduction. It has been continuously
      investigated as anticancer drug target for design and discovery of its
      inhibitors. Present studies aim to design novel heterocyclic/aryl substituted and
      adamantyl added thiosemicarbazones out fitted with improved cell permeability and
      effective RNR inhibition. Design strategy renders significant use of virtual
      screening and molecular docking studies to converge search of selective molecules
      for synthesis and further experimental studies. Selected candidates were
      synthesized and evaluated in vitro for their RNR inhibitory activity (IC50, uM)
      on MCF-7 cells, breast cancer cell lines. Molecular docking results (docking
      scores) and experimental results (IC50, uM) were found to be correlated and in
      agreement. Structure-based and ligandbased studies of results substantiate
      regulative role of water molecules at catalytic site (H2O: 2057) as well as at
      RNR inhibitor binding site (H2O: 2023, 2047, 2060 and 2070). Admantyl group has
      testified constant spatial position in docked poses and involved in steric
      interactions with Cys271, Asp272, Phe237, Gly234 and Val238. Heterocyclic/aryl
      substitutions equally offered H-bonds with water molecules (H2O: 2028, 2054, 2061
      and 2073) along with amino acids Ser264, Asp272, Tyr324 and Asn346. Present
      efforts to design new inhibitors incur new characteristics in RNR Inhibition.

PMID- 25579573
TI  - Phytochemical analyses and activity of herbal medicinal plants of North- East
      India for anti-diabetic, anti-cancer and anti-tuberculosis and their docking
      studies.
AB  - The traditional knowledge of medicinal plants that are in use by the indigenous
      Jaintia tribes residing in few isolated pockets of North-East India is documented
      here. The present study was carried out through the personal discussion with the
      president of the Jaintia Indigenous Herbal Medicine Association, Dr.H.Carehome
      Pakyntein from Jowai, Meghalaya. The plants being used generation after
      generation by his family of herbalists to cure ailments like tuberculosis, cancer
      and diabetes were selected for the present study. In order to scientifically
      validate the use of these selected plants for the cure of selected diseases,
      phytochemical analyses, characterization and molecular docking studies of some of
      the selected compounds from these plants have been carried out. The compounds 2
      hydroxy-4-methoxy- Benzaldehyde from methanolic extract of Strophanthus Wallichii
      and DL tetrahydropalmatine from Stephania Hernandifolia have been confirmed after
      determining their molecular structures, justifying the activity of these two
      plants against TB and cancer, respectively. The present study covers the
      potentials of some of the medicinal plants of North east India in curing common
      diseases due to which millions of people suffer and die. The presence of certain
      compounds in these plants related to the cure of the diseases deserves further
      studies. 

PMID- 25579574
TI  - Computational and experimental advances in drug repositioning for accelerated
      therapeutic stratification.
AB  - Drug repositioning is an important component of therapeutic stratification in the
      precision medicine paradigm. Molecular profiling and more sophisticated analysis
      of longitudinal clinical data are refining definitions of human diseases,
      creating needs and opportunities to re-target or reposition approved drugs for
      alternative indications. Drug repositioning studies have demonstrated success in
      complex diseases requiring improved therapeutic interventions as well as orphan
      diseases without any known treatments. An increasing collection of available
      computational and experimental methods that leverage molecular and clinical data
      enable diverse drug repositioning strategies. Integration of translational
      bioinformatics resources, statistical methods, chemoinformatics tools and
      experimental techniques (including medicinal chemistry techniques) can enable the
      rapid application of drug repositioning on an increasingly broad scale. Efficient
      tools are now available for systematic drug-repositioning methods using large
      repositories of compounds with biological activities. Medicinal chemists along
      with other translational researchers can play a key role in various aspects of
      drug repositioning. In this review article, we briefly summarize the history of
      drug repositioning, explain concepts behind drug repositioning methods, discuss
      recent computational and experimental advances and highlight available open
      access resources for effective drug repositioning investigations. We also discuss
      recent approaches in utilizing electronic health record for outcome assessment of
      drug repositioning and future avenues of drug repositioning in the light of
      targeting disease comorbidities, underserved patient communities, individualized
      medicine and socioeconomic impact. 

PMID- 25579575
TI  - An in silico approach for identification of novel inhibitors as a potential
      therapeutics targeting HIV-1 viral infectivity factor.
AB  - Currently available antiviral drugs target the pol-encoded retroviral enzymes or
      integrases, in addition, inhibitors that target HIV-1 envelope-receptor
      interactions have also been recently approved. Recent understanding of the
      interactions between HIV-1 and host restriction factors has provided fresh
      avenues for development of novel antiviral drugs. For example, viral infectivity
      factor (Vif) now surfaced as an important therapeutic target in treatment of HIV
      infection. Vif suppresses A3G antiviral activity by targeting these proteins for
      polyubiquitination and proteasomal degradation. In the present study we analyzed
      the inhibitory potential of VEC5 and RN18 to inhibit the Vif-A3G interaction
      through protein- protein docking studies. Perusal of the study showed that, VEC5
      and RN18 though inhibits the interaction however showed sub optimal potential. To
      overcome this set back, we identified 35 structural analogues of VEC5 and 18
      analogues of RN18 through virtual screening approach. Analogue with PubCID
      71624757 and 55358204 (AKOS006479723) -structurally akin to VEC5 and RN18
      respectively showed much appreciable interaction than their respective parent
      compound. Evident from Vif-A3G; protein - protein docking studies, analogue
      PubCID 71624757 demonstrated 1.08 folds better inhibitory potential than its
      parent compound VEC5 while analogue PubCID 55358204 was 1.15 folds better than
      RN18. Further these analogues passed drug likeness filters and predicted to be
      non- toxic. We expect these analogues can be put to pharmacodynamic studies that
      can pave way the breakthrough in HIV therapeutics. 

PMID- 25579576
TI  - Key points to consider when studying RNA remodeling by proteins.
AB  - Cellular RNAs depend on proteins for efficient folding to specific functional
      structures and for transitions between functional structures. This dependence
      arises from intrinsic properties of RNA structure. Specifically, RNAs possess
      stable local structure, largely in the form of helices, and they have abundant
      opportunities to form alternative helices and tertiary contacts and therefore to
      populate alternative structures. Proteins with RNA chaperone activity, either ATP
      dependent or ATP-independent, can promote structural transitions by interacting
      with single-stranded RNA (ssRNA) to compete away partner interactions and then
      release ssRNA so that it can form new interactions. In this chapter we review the
      basic properties of RNA and the proteins that function as chaperones and
      remodelers. We then use these properties as a foundation to explore key points
      for the design and interpretation of experiments that probe RNA rearrangements
      and their acceleration by proteins. 

PMID- 25579577
TI  - Happy birthday: 25 years of DEAD-box proteins.
AB  - RNA helicases of the DEAD-box family are found in all eukaryotes, most bacteria
      and many archaea. They play important roles in rearranging RNA-RNA and RNA
      protein interactions. DEAD-box proteins are ATP-dependent RNA binding proteins
      and RNA-dependent ATPases. The first helicases of this large family of proteins
      were described in the 1980s. Since then our perception of these proteins has
      dramatically changed. From bona fide helicases, they became RNA binding proteins
      that separate duplex RNAs, in a local manner, by binding and bending the target
      RNA. In the present review we describe some of the experiments that were
      important milestones in the life of DEAD-box proteins since their birth 25 years
      ago. 

PMID- 25579578
TI  - In vivo cross-linking followed by polyA enrichment to identify yeast mRNA binding
      proteins.
AB  - mRNA binding proteins regulate gene expression by controlling the processing,
      localization, decay, and translation of messenger RNAs (mRNAs). To fully
      understand this process, it is necessary to identify the complete set of mRNA
      binding proteins. This work describes a method for the systematic identification
      of yeast mRNA binding proteins. This method applies in vivo UV cross-linking,
      affinity pull-down of polyA(+) mRNAs, and analysis by mass spectrometry to
      identify proteins that directly bind to mRNAs. 

PMID- 25579579
TI  - Dynamics of the Spb4 interactome monitored by affinity purification.
AB  - RNA helicases constitute the largest class of NTPases involved in ribosome
      biogenesis, a fundamental process that has been best characterized in the
      eukaryotic model organism Saccharomyces cerevisiae. In yeast, genetic and
      biochemical analyses indicate that these RNA helicases are energy-consuming
      modulators of local structures inside pre-ribosomal particles that actively
      promote the establishment or dissociation of snoRNA:pre-rRNA base pairings, the
      activity of certain pre-rRNA nucleases, and/or the acquisition of pre-rRNA folds
      required for the recruitment or release of ribosome assembly factors and the
      stable assembly of ribosomal proteins. Despite significant recent advances, the
      precise molecular functions of RNA helicases involved in ribosome biogenesis
      remain largely elusive. In recent years, the purification and compositional
      analysis of distinct pre-ribosomal particles via affinity purification methods
      has been established as one of the most useful techniques to explore the yeast
      ribosome biogenesis pathway. In this chapter, we describe the use of different
      affinity purification methods to study the physical environment of RNA helicases
      involved in ribosome biogenesis, using as an example the putative RNA helicase
      Spb4 required for 60S ribosomal subunit biogenesis. 

PMID- 25579580
TI  - Using EMOTE to map the exact 5'-ends of processed RNA on a transcriptome-wide
      scale.
AB  - The presence or absence of structure in an RNA is often crucial to its function.
      This is evident for highly structured RNAs such as rRNA, tRNA, or riboswitches,
      but it is also the case for many mRNAs, where secondary structures in the 5' or
      3' UTR can determine the efficiency of translation or the half-life of the RNA.
      There are paths to modify such secondary structures, (1) by the action of a
      helicase that allows an alternative RNA structure to form, (2) by the formation
      of a duplex with another RNA, or (3) by cleavage of the RNA in a way that favors
      a different secondary structure. None of the three exclude the others, and in
      vivo it is common that two or all three work together to remodel an RNA to the
      desired form. However, while the first two solutions can be reversible, the
      cleavage of RNA is final, and there is no chance to go back. In this chapter, a
      method for tracking the 5' end created by RNA processing on a transcriptome-wide
      scale is presented. The Exact Mapping Of Transcriptome Ends (EMOTE) allows the
      large-scale identification of mono-phosphorylated RNA 5'-ends and provides the
      exact processing sites. 

PMID- 25579581
TI  - Cellular localization of RNA degradation and processing components in Escherichia
      coli.
AB  - The ability to study the localization and organization of proteins within the
      tiny cells of bacteria, such as Escherichia coli, has paved the way for a new and
      exciting era of prokaryotic cellular biology. Previously unrecognized levels of
      spatiotemporal and supramolecular organization of proteins have been revealed
      within the prokaryotic cell that had long been assumed as a "bag of enzymes."
      Immunofluorescence (IF) microscopy, which involves cellular immunostaining of
      native proteins with fluorescently labeled antibodies, is relatively laborious
      and requires cell fixation and highly specific antibodies. However, IF microscopy
      allows localization studies of native proteins expressed to their normal cellular
      levels, as opposed to labeling proteins with large fluorescent tag that can alter
      protein abundance dependent on changes in mRNAs and/or proteins stability, or
      whose detection can require overexpression of labeled proteins. In addition, when
      antibodies against native proteins are not available or lack specificity, epitope
      tags such as hemagglutinin (HA) or Flag can be used to label chromosomally
      expressed proteins. The short Flag- and HA-tag, eight or nine amino acids, are
      unlikely to interfere with the localization or function of the proteins. We
      describe and discuss here the use of fluorescence microscopy for determination of
      cellular organization of protein components of the E. coli RNA processing and
      degradation machinery. We present examples of cellular organization patterns
      visualized by light microscopy, either by IF microscopy of native and epitope
      tagged proteins in fixed cells, or by fluorescence labeling of the proteins in
      live cells. 

PMID- 25579582
TI  - Recombineering applications for the mutational analysis of bacterial RNA-binding
      proteins and their sites of action.
AB  - Genetics remains a powerful tool to study structure-function relationships in
      proteins and RNA. Structural elements important for the biological activity of
      these molecules can be dissected through the isolation of mutations and analysis
      of their effects on the mechanism under study. In suitable model organisms, this
      approach can greatly benefit from the ability to introduce mutations directly in
      the chromosomal context in ways that do not perturb neighboring sequences.
      Methods for performing such "markerless" site-directed chromosomal mutagenesis in
      bacteria have been developed in recent years. One such technique, used routinely
      in our laboratory, is described here. 

PMID- 25579583
TI  - Determination of RNA chaperone activity using an Escherichia coli mutant.
AB  - Bacterial cold shock proteins (CSPs) function as RNA chaperones that destabilize
      RNA secondary structures. A quadruple mutant of Escherichia coli (cspA, cspB,
      cspG, and cspE) displays a cold-sensitive growth phenotype. Plant cold shock
      domain (CSD) proteins have been shown to complement the cold-sensitive phenotype
      of the E. coli mutant and to share a function with E. coli CSPs as RNA
      chaperones. This methodology, which is detailed here, can be utilized to reveal
      or probe the RNA chaperone activity of heterologous proteins. 

PMID- 25579584
TI  - Biochemical characterization of G4 quadruplex telomerase RNA unwinding by the RNA
      helicase RHAU.
AB  - G4 quadruplexes are stable secondary structures prevalent in DNA and RNA that
      exhibit diverse regulatory functions. Herein, we describe an in vitro technique
      using the purified RNA helicase RHAU to unwind a G4 quadruplex identified near
      the 5' end of the human telomerase RNA (hTR). A synthetic RNA corresponding to
      the quadruplex forming region of hTR (hTR10-43), as well as a predicted
      complementary strand (25P1), are combined in a reaction containing the purified
      helicase and ATP. Reaction products and appropriate controls are resolved by
      native gel electrophoresis. Gels can be stained using a combination of total RNA
      and quadruplex-specific dyes to observe the expected quadruplex to duplex
      conversion. This straightforward method can be extended to study structural
      changes in other inter- or intramolecular quadruplex containing DNA/RNA molecules
      with the RHAU helicase or other RNA/DNA remodeling enzymes. 

PMID- 25579585
TI  - ATPase site configuration of the RNA helicase DbpA probed by ENDOR spectroscopy.
AB  - Electron-nuclear double resonance (ENDOR) is a method that probes the local
      structure of paramagnetic centers via their hyperfine interactions with nearby
      magnetic nuclei. Here we describe the use of this technique to structurally
      characterize the ATPase active site of the RNA helicase DbpA, where Mg(2+)-ATP
      binds. This is achieved by substituting the EPR (electron paramagnetic resonance)
      silent Mg(2+) ion with paramagnetic, EPR active, Mn(2+) ion. (31)P ENDOR provides
      the interaction of the Mn(2+) with the nucleotide (ADP, ATP and its analogs)
      through the phosphates. The ENDOR spectra clearly distinguish between ATP- and
      ADP-binding modes. In addition, by preparing (13)C-enriched DbpA, (13)C ENDOR is
      used to probe the interaction of the Mn(2+) with protein residues. This
      combination allows tracking structural changes in the Mn(2+) coordination shell,
      in the ATPase site, in different states of the protein, namely with and without
      RNA and with different ATP analogs. Here, a detailed description of sample
      preparation and the ENDOR measurement methodology is provided, focusing on
      measurements at W-band (95 GHz) where sensitivity is high and spectral
      interpretations are relatively simple. 

PMID- 25579586
TI  - Bioinformatics and biochemical methods to study the structural and functional
      elements of DEAD-box RNA helicases.
AB  - DEAD-box RNA helicases have core structures consisting of two, tandemly linked,
      RecA-like domains that contain all of the conserved motifs involved in binding
      ATP and RNA, and that are needed for the enzymatic activities. The conserved
      sequence motifs and structural homology indicate that these proteins share common
      origins and underlining functionality. Indeed, the purified proteins generally
      act as ATP-dependent RNA-binding proteins and RNA-dependent ATPases in vitro, but
      for the most part without the substrate specificity or enzymatic regulation that
      exists in the cell. We are interested in understanding the relationships between
      the conserved motifs and structures that confer the commonly shared features, and
      we are interested in understanding how modifications of the core structure alter
      the enzymatic properties. We use sequence alignments and structural modeling to
      reveal regions of interest, which we modify by classical molecular biological
      techniques (mutations and deletions). We then use various biochemical techniques
      to characterize the purified proteins and their variants for their ATPase, RNA
      binding, and RNA unwinding activities to determine the functional roles of the
      different elements. In this chapter, we describe the methods we use to design our
      constructs and to determine their enzymatic activities in vitro. 

PMID- 25579588
TI  - A FRET-based, continuous assay for the helicase activity of DEAD-box proteins.
AB  - Enzymes from cold-adapted organisms are generally endowed with lower activation
      enthalpies than their counterparts from organisms growing at higher temperatures,
      making them better catalysts in the cold. However, the enzymes of RNA metabolism
      have not been examined in this respect. A challenge for studying cold adaptation
      of DEAD-box RNA helicases is the low precision of the classical, discontinuous
      helicase assay based on electrophoretic separation of duplexes and isolated
      strands. Here, we describe a continuous, FRET-based assay that allows the
      measurement of the helicase activities of DEAD-box proteins with a precision high
      enough to detect changes in activation enthalpies associated with cold
      adaptation. 

PMID- 25579587
TI  - Measuring helicase inhibition of the DEAD-box protein Dbp2 by Yra1.
AB  - Despite the highly conserved helicase core, individual DEAD-box proteins are
      specialized in diverse RNA metabolic processes. One mechanism that determines
      DEAD-box protein specificity is enzymatic regulation by other protein cofactors.
      In this chapter, we describe a protocol for purifying the Saccharomyces
      cerevisiae DEAD-box RNA helicase Dbp2 and RNA-binding protein Yra1 and subsequent
      analysis of helicase regulation. The experiments described here can be adapted to
      other RNA helicases and their purified cofactor(s). 

PMID- 25579589
TI  - A fluorescence-based screening assay for identification of hepatitis C virus NS3
      helicase inhibitors and characterization of their inhibitory mechanism.
AB  - Hepatitis C virus (HCV) can establish a chronic infection in the majority of
      individuals infected, resulting in liver cirrhosis and hepatocellular carcinoma.
      Because the current standard treatment for HCV infection has limitations in terms
      of severe side effects, the emergence of drug resistance, and drug-drug
      interactions, it is desirable to develop novel antivirals that target viral
      proteins involved in viral replication. HCV nonstructural protein 3 (NS3)
      helicase, which unwinds double-stranded nucleic acids to yield single-stranded
      nucleic acids, is one possible target for new drug development, because it plays
      an essential role in viral replication. In this chapter, we describe a helicase
      assay based on fluorescence resonance energy transfer (FRET) that can be used for
      high-throughput screening of HCV NS3 helicase inhibitors. The assay uses a double
      stranded RNA (dsRNA) substrate with a fluorophore-labeled strand hybridized to a
      quencher-labeled strand and monitors the increase in fluorescence intensity
      resulting from helicase-catalyzed unwinding of the dsRNA substrate. We further
      describe radioactive assays to directly visualize RNA strands unwound by helicase
      and to evaluate the ATPase and RNA-binding activities of NS3, which are linked to
      helicase activity, for characterization of the inhibitory mechanism. 

PMID- 25579590
TI  - Mechanisms of HCV NS3 helicase monitored by optical tweezers.
AB  - As one of the essential enzymes for viral genome replication, the hepatitis C
      virus NS3 helicase is one of the best characterized RNA helicases to date in
      understanding the mechanistic cycles in a helicase-catalyzed strand separation
      reaction. Recently, single-molecule studies on NS3, in particular the use of
      optical tweezers with sub-base pair spatial resolution, have allowed people to
      examine the potential elementary steps of NS3 in unwinding the double-stranded
      RNA fueled by ATP binding and hydrolysis. In this chapter, I detail the essential
      technical elements involved in conducting a high-resolution optical tweezers
      study of NS3 helicase, starting from the purification of the recombinant helicase
      protein from E. coli to setting up a high-resolution single-molecule experiment
      using optical tweezers. 

PMID- 25579591
TI  - Constructing a magnetic tweezers to monitor RNA translocation at the single
      molecule level.
AB  - Single-molecule methods have become an invaluable tool in the investigation of
      the mechanisms of nucleic-acid motors. Magnetic tweezers is a single-molecule
      manipulation technique that permits the real-time measurement of enzyme
      activities on single nucleic-acid molecules at high-resolution, high-throughput,
      and inherently constant force. Here, we describe several aspects of the
      implementation of magnetic tweezers, with special emphasis on the construction of
      a simple magnetic trap and, in particular, on the detailed description of image
      analysis methods to measure the extension changes in nucleic-acid molecules
      induced by protein activity. Finally, we carefully describe the steps involved in
      performing a full magnetic tweezers experiment. 

PMID- 25579592
TI  - Probing RNA translocases with DNA.
AB  - For some helicases, it is possible to investigate RNA translocase activity on DNA
      substrates because the enzyme acts on both substrates. Potassium permanganate
      (KMnO4) footprinting is a method used to chemically probe the conformation of DNA
      as well as the binding of proteins. Combining footprinting methods with rapid
      mixing methods that utilize a chemical quench-flow instrument can enable tracking
      of the translocase with nucleotide resolution. 

PMID- 25579593
TI  - Monitoring RNA unwinding by the transcription termination factor Rho from
      Mycobacterium tuberculosis.
AB  - Transcription termination factor Rho is a ring-shaped, homo-hexamieric RNA
      translocase that dissociates transcription elongation complexes and
      transcriptional RNA-DNA duplexes (R-loops) in bacteria. The molecular mechanisms
      underlying these biological functions have been essentially studied with Rho
      enzymes from Escherichia coli or close Gram-negative relatives. However, phylo
      divergent Rho factors may have distinct properties. Here, we describe methods for
      the preparation and in vitro characterization (ATPase and helicase activities) of
      the Rho factor from Mycobacterium tuberculosis, a specimen with uncharacteristic
      molecular and enzymatic features. These methods set the stage for future studies
      aimed at better defining the diversity of enzymatic properties of Rho across the
      bacterial kingdom. 

PMID- 25579594
TI  - Characterization of the mechanisms of transcription termination by the helicase
      Sen1.
AB  - In vitro transcription systems have been widely used to study all the steps of
      transcription from initiation to termination and many transcription-coupled
      processes. Here we describe an in vitro transcription-termination assay that we
      have used for the analysis of the mechanism of termination by the yeast helicase
      Sen1. In this system, we use highly purified proteins to assemble ternary
      elongation complexes (RNA polymerase, DNA template, and nascent RNA) on
      biotinylated DNA that is subsequently immobilized on streptavidin beads. After
      allowing transcription by the addition of nucleotides, the termination events can
      be detected and quantified by comparing the amounts of polymerases and
      transcripts released from the DNA templates in reactions performed in the absence
      or in the presence of purified Sen1. By modifying different parameters of the
      assay, this technique allows the study of several aspects of the termination
      reaction. 

PMID- 25579596
TI  - Single-molecule FRET characterization of RNA remodeling induced by an
      antitermination protein.
AB  - Single-molecule Forster Resonance Energy Transfer (smFRET) is a useful technique
      to probe conformational changes within bio-macromolecules. Here, we introduce how
      to perform smFRET measurements in solution to investigate RNA remodeling and RNA
      protein interactions. In particular, we focus on how the close-to-open transition
      of an antiterminator hairpin is influenced by the binding of the antitermination
      protein and the competition by oligonucleotides. 

PMID- 25579595
TI  - Characterization of TRAP-mediated regulation of the B. subtilis trp operon using
      in vitro transcription and transcriptional reporter fusions in vivo.
AB  - In Bacillus subtilis, transcription of the tryptophan biosynthetic operon is
      regulated by an attenuation mechanism involving two alternative RNA secondary
      structures in the 5' leader region upstream of the structural genes. Regulation
      is accomplished, at least in part, by controlling which RNA structure forms
      during transcription of the operon. When intracellular tryptophan levels are
      high, the trp RNA-binding attenuation protein (TRAP) binds to the nascent trp
      mRNA to promote formation of a transcription terminator structure so as to induce
      transcription termination prior to the structural genes. In limiting tryptophan,
      TRAP does not bind, the alternative antiterminator RNA structure forms, and the
      operon is transcribed. Several in vitro and in vivo assays have been utilized to
      study TRAP-mediated regulation of both transcription and translation. Here, we
      describe using in vitro transcription attenuation assays and in vivo trp-lacZ
      fusions to examine TRAP-mediated regulation of the trp genes. 

PMID- 25579597
TI  - Fluorescence reporters for Hfq oligomerization and RNA annealing.
AB  - Fluorescence spectroscopy is a sensitive technique for detecting protein-protein,
      protein-RNA, and RNA-RNA interactions, requiring only nanomolar concentrations of
      labeled components. Fluorescence anisotropy provides information about the
      assembly of multi-subunit proteins, while molecular beacons provide a sensitive
      and quantitative reporter for base pairing between complementary RNAs. Here we
      present a detailed protocol for labeling Hfq protein with cyanine 3-maleimide and
      dansyl chloride to study the protein oligomerization and RNA binding by semi
      native polyacrylamide gel electrophoresis (PAGE) and fluorescence anisotropy. We
      also present a detailed protocol for measuring the rate of annealing between a
      molecular beacon and a target RNA in the presence of Hfq using a stopped-flow
      spectrometer. 

PMID- 25579598
TI  - Fluorescence anisotropy-based salt-titration approach to characterize protein
      nucleic acid interactions.
AB  - Many proteins bind nucleic acids (NA) via cationic residues that interact
      electrostatically with the anionic phosphate backbone of RNA or DNA. These
      electrostatic interactions are often insensitive to NA sequence and structure,
      but confer strong salt dependence to the binding interactions. In contrast, salt
      independent non-electrostatic contacts reflect more specific binding
      interactions. Proteins with multiple cationic NA-binding domains connected by
      flexible linkers, such as the HIV-1 Gag polyprotein, may bind different NA
      molecules in distinct ways. For example, Gag binding to the Psi-packaging signal
      of the HIV-1 RNA genome optimizes the specific non-electrostatic binding
      component of this protein-RNA interaction. In contrast, Gag binding to a non-psi
      RNA optimizes the electrostatic interactions at the expense of specific contacts.
      Here, we describe a fluorescence anisotropy-based salt-titration approach that
      allows complete characterization of both electrostatic and non-electrostatic
      binding components for any protein-NA complex in a quantitative manner within a
      single assay. 

PMID- 25579599
TI  - Probing Hfq:RNA interactions with hydroxyl radical and RNase footprinting.
AB  - RNA footprinting and structure probing techniques are used to characterize the
      interaction between RNA-binding proteins and RNAs in vitro. Hydroxyl radical
      footprinting results in the identification of protein binding site(s) in an RNA.
      Ribonuclease (RNase) structure probing is a complementary technique that also
      provides information about protein binding sites, as well as RNA structure and
      possible protein-directed RNA remodeling. Here we provide a comprehensive
      protocol for studying the interaction between Hfq and an mRNA or sRNA of interest
      using a combination of RNase A, T1, and V1 as well as hydroxyl radical
      footprinting techniques. Detailed protocols for in vitro synthesis of (32)P
      labeled RNA; formation of Hfq:RNA binary complex(es), RNase, and hydroxyl radical
      footprinting; preparation and running of sequencing gels; and data analysis are
      provided. 

PMID- 25579600
TI  - Purification of eukaryotic exoribonucleases following heterologous expression in
      bacteria and analysis of their biochemical properties by in vitro enzymatic
      assays.
AB  - Exoribonucleases-among the other RNases-play a crucial role in the regulation of
      different aspects of RNA metabolism in the eukaryotic cell. To fully understand
      the exact mechanism of activity exhibited by such enzymes, it is crucial to
      determine their detailed biochemical properties, notably their substrate
      specificity and optimal conditions for enzymatic action. One of the most
      significant features of exoribonucleases is the direction of degradation of RNA
      substrates, which can proceed either from 5'-end to 3'-end or in the opposite
      way. Here, we present methods allowing the efficient production and purification
      of eukaryotic exoribonucleases, the preparation and labeling of various RNA
      substrates, and the biochemical characterization of exonucleolytic activity. We
      also explain how the exonucleolytic activity may be distinguished from that of
      endonucleases. 

PMID- 25579601
TI  - Tips and tricks to probe the RNA-degrading activities of hyperthermophilic
      archaeal beta-CASP ribonucleases.
AB  - The importance of ribonucleases in posttranscriptional control of gene expression
      has been established in Eukarya and Bacteria for over a decade. However, this
      process has been overlooked in Archaea, which are of universal importance to
      elucidate fundamental biological mechanisms and to study the evolution of life on
      Earth. Very few ribonucleolytic activities have been reported in Archaea, and RNA
      metabolism pathways wait to be described. Recently we have identified two major
      groups of archaeal ribonucleases, aCPSF1 and aRNase J, which are members of the
      beta-CASP metallo-beta-lactamase family. Here, we describe in vitro methods to
      characterize the endo- and exoribonucleolytic activities of hyperthermophilic
      archaeal beta-CASP ribonucleases. The use of various labeled RNA substrates
      allows defining the specificity of RNA cleavage and the directionality of the
      exoribonucleolytic trimming activity of the archaeal enzymes which work at high
      temperature. Elucidating in vitro ribonucleolytic activities is one step toward
      the understanding of the role of beta-CASP ribonucleases in RNA metabolism
      pathways in archaeal cells. 

PMID- 25579602
TI  - Does joint architecture influence the nature of intra-articular fractures?
AB  - INTRODUCTION: The architecture of joints has potentially the greatest influence
      on the nature of intra-articular fractures. We analysed a large number of intra
      articular fractures with two aims: (1) to determine if the pattern of injuries
      observed supports our conjecture that the local skeletal architecture is an
      important factor and (2) to investigate whether associated dislocations further
      affect the fracture pattern. METHODS: A retrospective study of intra-articular
      fractures over a 3.5-year period; 1003 joints met inclusion criteria and were
      analysed. Three independent investigators determined if fractures affected the
      convex dome, the concave socket, or if both joint surfaces were involved. Further
      review determined if a joint dislocation occurred with the initial injury.
      Statistical analysis was performed using a one-way frequency table, and the
      chi(2) test was used to compare the frequencies of concave and convex surface
      fractures. The odds ratios (ORs) were calculated to establish the association
      between the frequencies of concave and convex surface fractures, as well as
      between dislocation and either fracture surface involvement. RESULTS: Of the 1003
      fractures analysed, 956 (95.3%) involved only the concavity of the joint; in 21
      fractures (2.1%) both joint surfaces were involved; and in 26 fractures (2.6%)
      only the convexity was involved (chi(2)=1654.9, df=2, p<0.0001). As expected, the
      concavity was 20.8 times more likely to fail than the convexity (11.2-36.6, 95%
      CI). However, the risk of fracturing the convex surface was 18.6 times higher
      (9.8-35.2, 95% CI) in association with a simultaneous joint dislocation, compared
      to those cases without a joint dislocation. CONCLUSIONS: These results very
      strongly support the study hypotheses: the skeletal architecture of joints
      clearly plays a highly significant role in determining the nature of intra
      articular fractures. Intra-articular fractures involving the convexity are much
      more likely to be associated with a concurrent joint dislocation.

PMID- 25579603
TI  - Minimally invasive technique for medial subtalar dislocation associated with
      navicular and entire posterior talar process fracture: a case report.
AB  - This is a case report of 31-year-old woman who sustained medial subtalar
      dislocation with navicular and entire posterior talar process fracture. After
      closed reduction of the subtalar dislocation, compute tomography (CT)
      demonstrated that the talus fracture involved the entire posterior process and
      navicular. The fracture of the talus was fixed with a cannulated screw and the
      navicular was held with two K-wires to the main body using with a minimally
      invasive approach. Follow-up revealed that the functional and radiographic
      results were graded as good. 

PMID- 25579604
TI  - A comparison of 30-day complications following plate fixation versus
      intramedullary nailing of closed extra-articular tibia fractures.
AB  - BACKGROUND AND PURPOSE: Tibial shaft fractures are often treated by
      intramedullary nailing (IMN) or plate fixation. Our purpose was to compare the 30
      day complication rates between IMN and plate fixation of extra-articular tibial
      fractures. MATERIALS AND METHODS: We conducted a retrospective analysis of
      prospectively collected patient demographics, comorbidities, and 30 day
      complications of isolated closed extra-articular tibial shaft fractures from 2006
      to 2012 using the American College of Surgeon's National Surgical Quality
      Improvement Program (ACS-NSQIP) database. A 1:2 propensity-matched dataset was
      created to control for differences in preoperative demographics and comorbidities
      across the plate fixation and IMN groups. Univariate and multivariate analyses
      were used to assess differences in complications between the groups and the
      independent effects of plate fixation or IMN on complications. RESULTS: A total
      of 771 patients were identified with 234 (30.4%) in the plate fixation and 537
      (69.6%) in the IMN group. We found no statistical difference in rates of wound
      complications, medical complications, reoperation, or mortality in our propensity
      matched analyses. Plate fixation was found to be independently associated with a
      lower risk of postoperative blood transfusion compared to IMN (odds ratio 0.326,
      p=0.032). Plate fixation was not independently associated with any other examined
      complications. CONCLUSIONS: We found no difference in 30-day postoperative
      complications between plate fixation and intramedullary nailing of isolated extra
      articular tibia fractures with the exception of decreased postoperative
      transfusion requirements with plate fixation. We conclude that both procedures
      offer a similar short-term complication profile.

PMID- 25579605
TI  - Unravelling the temporal association between lameness and body condition score in
      dairy cattle using a multistate modelling approach.
AB  - Recent studies have reported associations between lameness and body condition
      score (BCS) in dairy cattle, however the impact of change in the dynamics of BCS
      on both lameness occurrence and recovery is currently unknown. The aim of this
      longitudinal study was to investigate the effect of change in BCS on the
      transitions from the non-lame to lame, and lame to non-lame states. A total of
      731 cows with 6889 observations from 4 UK herds were included in the study.
      Mobility score (MS) and body condition score (BCS) were recorded every 13-15 days
      from July 2010 until December 2011. A multilevel multistate discrete time event
      history model was built to investigate the transition of lameness over time.
      There were 1042 non-lame episodes and 593 lame episodes of which 50% (519/1042)
      of the non-lame episodes transitioned to the lame state and 81% (483/593) of the
      lame episodes ended with a transition to the non-lame state. Cows with a lower
      BCS at calving (BCS Group 1 (1.00-1.75) and Group 2 (2.00-2.25)) had a higher
      probability of transition from non-lame to lame and a lower probability of
      transition from lame to non-lame compared to cows with BCS 2.50-2.75, i.e. they
      were more likely to become lame and if lame, they were less likely to recover.
      Similarly, cows who suffered a greater decrease in BCS (compared to their BCS at
      calving) had a higher probability of becoming lame and a lower probability of
      recovering in the next 15 days. An increase in BCS from calving was associated
      with the converse effect, i.e. a lower probability of cows moving from the non
      lame to the lame state and higher probability of transition from lame to non
      lame. Days in lactation, quarters of calving and parity were associated with both
      lame and non-lame transitions and there was evidence of heterogeneity among cows
      in lameness occurrence and recovery. This study suggests loss of BCS and increase
      of BCS could influence the risk of becoming lame and the chance of recovery from
      lameness. Regular monitoring and maintenance of BCS on farms could be a key tool
      for reducing lameness. Further work is urgently needed in this area to allow a
      better understanding of the underlying mechanisms behind these relationships. 

PMID- 25579607
TI  - Identification of rod- and cone-specific expression signatures to identify
      candidate genes for retinal disease.
AB  - Recent advances in technology have greatly increased our ability to identify
      genetic variants in individuals with retinal disease. However, determining which
      are likely to be pathogenic remains a challenging task. Using a transgenic
      coneless (cl) mouse model, together with rodless (rd/rd) and rodless/coneless
      (rd/rd cl) mice, we have characterised patterns of gene expression in the rod and
      cone photoreceptors at a genome-wide level. We examined the expression of >27,000
      genes in the mice lacking rods, cones or both and compared them with wild type
      animals. We identified a list of 418 genes with highly significant changes in
      expression in one or more of the transgenic strains. Pathway analysis confirmed
      that expected Gene Ontology terms such as phototransduction were over-represented
      amongst these genes. However, many of these genes have no previously known
      function in the retina. Gene set enrichment analysis further demonstrated that
      the mouse orthologues of known human retinal disease genes were significantly
      enriched amongst those genes with decreased expression. Comparison of our data to
      human disease loci with no known causal genetic changes has highlighted genes
      with significant changes in expression making these strong candidates for further
      screening. These data add to the current literature through the utilisation of
      the specific cl and rd/rd cl models. Moreover, this study identifies genes that
      appear to be implicated in photoreceptor function thereby providing a valuable
      filter for variants identified by high-throughput sequencing in individuals with
      retinal disease. 

PMID- 25579606
TI  - Tear metabolite changes in keratoconus.
AB  - While efforts have been made over the years, the exact cause of keratoconus (KC)
      remains unknown. The aim of this study was to identify alterations in endogenous
      metabolites in the tears of KC patients compared with age-matched healthy
      subjects. Three groups were tested: 1) Age-matched controls with no eye disease
      (N = 15), 2) KC - patients wearing Rigid Gas permeable lenses (N = 16), and 3) KC
      - No Correction (N = 14). All samples were processed for metabolomics analysis
      using LC-MS/MS. We identified a total of 296 different metabolites of which >40
      were significantly regulated between groups. Glycolysis and gluconeogenesis had
      significant changes, such as 3-phosphoglycerate and 1,3 diphosphateglycerate. As
      a result the citric acid cycle (TCA) was also affected with notable changes in
      Isocitrate, aconitate, malate, and acetylphosphate, up regulated in Group 2
      and/or 3. Urea cycle was also affected, especially in Group 3 where ornithine and
      aspartate were up-regulated by at least 3 fold. The oxidation state was also
      severely affected. Groups 2 and 3 were under severe oxidative stress causing
      multiple metabolites to be regulated when compared to Group 1. Group 2 and 3,
      both showed significant down regulation in GSH-to-GSSG ratio when compared to
      Group 1. Another indicator of oxidative stress, the ratio of lactate - pyruvate
      was also affected with Groups 2 and 3 showing at least a 2-fold up regulation.
      Overall, our data indicate that levels of metabolites related to urea cycle, TCA
      cycle and oxidative stress are highly altered in KC patients. 

PMID- 25579608
TI  - Strong-field plasmonic photoemission in the mid-IR at <1 GW/cm2 intensity.
AB  - We investigated nonlinear photoemission from plasmonic films with femtosecond,
      mid-infrared pulses at 3.1 MUm wavelength. Transition between regimes of multi
      photon-induced and tunneling emission is demonstrated at an unprecedentedly low
      intensity of <1 GW/cm(2). Thereby, strong-field nanophysics can be accessed at
      extremely low intensities by exploiting nanoscale plasmonic field confinement,
      enhancement and ponderomotive wavelength scaling at the same time. Results agree
      well with quantum mechanical modelling. Our scheme demonstrates an alternative
      paradigm and regime in strong-field physics.

PMID- 25579609
TI  - Training less threatening interpretations over the Internet: Does the number of
      missing letters matter?
AB  - BACKGROUND AND OBJECTIVES: Cognitive Bias Modification to reduce threat
      interpretations (CBM-I) trains individuals to resolve ambiguous scenarios via
      completion of word fragments that assign benign meanings to scenarios. The
      current study tested: 1) whether Internet-based CBM-I can shift interpretations
      to be more positive/less negative, and 2) whether varying the number of letters
      missing in the word fragments (assumed to increase task difficulty) moderates CBM
      I's effects. METHODS: Participants (N = 350) completed a brief online version of
      CBM-I, followed by assessments of interpretation bias, fear of negative
      evaluation, and anticipatory anxiety. Participants were randomly assigned to 1 of
      5 conditions: control (half of scenarios ended positively, half negatively), or 4
      positive conditions (all scenarios ended positively, but word fragments varied on
      number of letters missing, from 0 to 3). RESULTS: Relative to the control
      condition, all positive conditions led to more positive/less negative
      interpretations. When analyses were re-run with only a highly socially anxious
      subset of the sample (n = 100), conditions in which the final word of scenarios
      was missing 0, 1, or 2 letters led to more positive/less negative interpretations
      compared to the control condition, but the condition missing 3 letters did not
      differ from the control condition. There were no differences between conditions
      on other outcome measures. LIMITATIONS: Training was brief, and an unselected
      sample was used. CONCLUSIONS: Results suggest a brief Internet-based CBM-I
      paradigm can shift interpretation bias, but not necessarily other anxiety
      relevant outcomes. Making the task too difficult may blunt effects for highly
      socially anxious individuals.

PMID- 25579610
TI  - The lipoprotein lipase S447X and cholesteryl ester transfer protein rs5882
      polymorphisms and their relationship with lipid profile in human serum of obese
      individuals.
AB  - BACKGROUND: Obesity is often associated with an alter lipid profile, e.g., raised
      serum triglycerides (TG) and low high-density lipoprotein (HDL) cholesterol
      levels, both important risk factor for cardiovascular-diseases. The aim of
      current study was to explore the association of a polymorphism of the lipoprotein
      lipase (LPL) rs328 and cholesteryl-ester-transfer-protein (CETP) rs5882 genes in
      relation to lipid profile in subjects with/without obesity. SUBJECTS/METHODS:
      Genotyping was carried out in 271 individuals, (151 obese subjects and 120 non
      obese). Univariate/multivariate analyses were conducted to evaluate the
      association of these genetic-polymorphisms with obesity and lipid components.
      RESULTS: Obese subjects had a significantly (P<0.05) higher level of triglyceride
      (TG), blood pressure, waist-circumference and fasting-blood-glucose, and lower
      level of HDL-C. LPL and CETP polymorphisms were not associated with obesity in
      our population. However, the LPL rs328-GG-GC genotype was significantly related
      to a higher concentration of TG, compared to the CC wild-type; and a higher HDL-C
      level in the obesity-group with respect to the control group. Moreover, obese
      subjects carrying the G allele of CETP had a significantly lower level of HDL-C
      (P<0.05) compared to those with C allele. CONCLUSION: We demonstrate a
      significant association of LPL and CETP polymorphisms with serum triglycerides
      and HDL-cholesterol.

PMID- 25579611
TI  - Belgian guidelines for budget impact analyses.
AB  - OBJECTIVES: To develop methodological guidelines for budget impact analysis
      submitted to the Belgian health authorities as part of a reimbursement request.
      METHODS: A review of the literature was performed and provided the basis for
      preliminary budget impact guidelines. These guidelines were improved after
      discussion with health economists from the Belgian Health Care Knowledge Centre
      (KCE) and different Belgian stakeholders from both government and industry.
      Preliminary guidelines were also discussed in a workshop with health economists
      from The German Institute for Quality and Efficiency in Healthcare. Finally, the
      guidelines were also externally validated by three external experts. RESULTS: The
      guidelines give explicit guidance for the following components of a budget impact
      analysis: perspective of the evaluation, target population, comparator, costs,
      time horizon, modeling, handling uncertainty and discount rate. Special attention
      is given to handling varying target population sizes over time, applying a time
      horizon up to the steady state instead of short-term predictions, and
      similarities and differences between budget impact analysis and economic
      evaluations. CONCLUSION: The guidelines provide a framework for both researchers
      and assessors to set up budget impact analyses that are transparent, relevant, of
      high quality and apply a consistent methodology. This might improve the extent to
      which such evaluations can reliably and consistently be used in the reimbursement
      decision making process.

PMID- 25579612
TI  - Anisotropic swelling of thin gel sheets.
AB  - We describe the anisotropic swelling within the Flory-Rehner thermodynamic model
      through an extension of the elastic component of the free-energy, which takes
      into account the oriented hampering of the swelling-induced deformations due to
      the presence of stiffer fibers. We also characterize the homogeneous free
      swelling solutions of the corresponding anisotropic stress-diffusion problem, and
      discuss an asymptotic approximation of the key equations, which allows us to
      explicitly derive the anisotropic solution of the problem. We propose a proof-of
      concept of our model, realizing thin bilayered gel sheets with layers having
      different anisotropic structures. In particular, for seedpod-like sheets, we
      observe and quantitatively measure the helicoid versus ribbon transition
      determined by the aspect ratio of the composite sheet. 

PMID- 25579618
TI  - Combined Anti e and Anti C Rh Isoimmunisation and Severe Hyperbilirubinemia.

PMID- 25579619
TI  - Denhaminols A-H, dihydro-beta-agarofurans from the endemic Australian rainforest
      plant Denhamia celastroides.
AB  - Eight new dihydro-beta-agarofurans, denhaminols A-H (1-8), were isolated from the
      leaves of the Australian rainforest tree Denhamia celastroides. The chemical
      structures of 1-8 were elucidated following analysis of 1D/2D NMR and MS data.
      The absolute configuration of denhaminol A (1) was determined by single-crystal X
      ray crystallography. All compounds were evaluated for cytotoxic activity against
      the human prostate cancer cell line LNCaP, using live-cell imaging and metabolic
      assays. Denhaminols A (1) and G (7) were also tested for their effects on the
      lipid content of LNCaP cells. This is the first report of secondary metabolites
      from D. celastroides. 

PMID- 25579620
TI  - A mobile phone application for the collection of opinion data for forest planning
      purposes.
AB  - The last 30 years has seen an increase in environmental, socio-economic, and
      recreational objectives being considered throughout the forest planning process.
      In the Finnish context these are considered mainly at the regional level
      potentially missing out on more local issues and problems. Such local information
      would be most efficiently collected with a participatory GIS approach. A mobile
      participatory GIS application called Tienoo was developed as a tool for
      collecting location-specific opinions of recreational and aesthetical
      characteristics of forests and forest management. The application also contains
      information the user can access regarding the practical details of the area, for
      instance about the recreational infrastructure. The application was tested in
      Ruunaa National Hiking Area, North Karelia, Eastern Finland. Through this
      application it is possible to continuously collect geolocated preference
      information. As a result, the collected opinions have details which can be
      located in both time and space. This allows for the possibility to monitor the
      changes in opinions when the stands are treated, and it also allows for easily
      analyzing the effect of time of year on the opinions. It is also possible to
      analyze the effect of the spatial location and the forest characteristics on the
      opinions using GIS analysis.

PMID- 25579621
TI  - Experiential benefits, place meanings, and environmental setting preferences
      between proximate and distant visitors to a national scenic trail.
AB  - Effective management of conserved natural areas often requires a good
      understanding of recreation visitors who possess various values for those areas.
      This study examined differences in experiential benefits sought, place meanings,
      and environmental setting preferences between proximate and distant visitors to a
      publicly managed national scenic trail, which transects a variety of conserved
      public lands. Data were collected using on-site post-hike interviews with
      visitors at low, moderate, and high use trailheads. Proximate visitors sought
      mental and physical health more strongly than distant visitors, while distant
      visitors sought environmental exploration more strongly than proximate visitors.
      No significant difference in family bonding and achievement benefits existed
      between the two groups. Meanings related to place dependence, family identity,
      community identity, and place identity were more strongly ascribed by proximate
      visitors, and both groups rated ecological integrity meanings highly. Distant
      visitors showed stronger tendencies toward preferring a lesser level of trail
      development, lower level of encounters with other groups, and higher level of
      natural landscapes, which indicated an inclination toward natural settings. These
      findings indicate a managerially relevant role of the degree of proximity to
      environmental resources on individuals' recreation behaviors, meanings ascribed
      to the resources and setting conditions. Understanding differences and
      similarities between groups dichotomized by proximity to natural resources should
      advance more effective management of recreation and benefit opportunities for
      diverse visitor groups. 

PMID- 25579622
TI  - Erratum to "Analysis of Nucleotide Sequences of the 16S rRNA Gene of Novel
      Escherichia coli Strains Isolated from Feces of Human and Bali Cattle".
AB  - [This corrects the article DOI: 10.1155/2014/475754.]. 

PMID- 25579623
TI  - Group medical consultations in the follow-up of breast cancer: a randomized
      feasibility study.
AB  - PURPOSE: Group medical consultations (GMCs) provide individual medical visits
      conducted within a group of four to eight peer patients. This study evaluated the
      feasibility and efficacy of GMCs in the follow-up of breast cancer. METHODS: In
      this randomized controlled trial, 38 patients participated in a single GMC
      (intervention group), while the control group (n = 31) received individual
      outpatient visits. Feasibility is measured in terms of acceptability, demand,
      practicability and costs, integration and implementation, and efficacy. Between
      group differences on the efficacy outcomes distress (SCL-90) and empowerment
      (CEQ), 1 week and 3 months after the visit, were analyzed using ANCOVAs. RESULTS:
      GMCs scored high on most areas of feasibility. Patients in GMCs and individual
      visits were equally satisfied. Patients and professionals reported more discussed
      themes in GMCs, despite no between-group differences on information needs prior
      to the visit. Sixty-nine percent of GMC patients experienced peer support. Costs
      for GMCs were higher compared to individual visits. However, involving a clinical
      nurse specialist (CNS) instead of a medical specialist reduced costs to the level
      of individual CNS care. Efficacy outcomes (distress and empowerment) were equal
      in both groups. CONCLUSION: GMCs in this study were feasible. Further
      optimization of GMCs in future (cost-)effectiveness trials is possible by
      increasing the frequency of GMCs, stating criteria for the type of professionals,
      number of patients involved, and time limits. IMPLICATIONS FOR CANCER SURVIVORS:
      BCS may benefit from GMCs by receiving more information and additional peer
      support. GMCs cover all aspects of follow-up and may be a good alternative for
      individual follow-up.

PMID- 25579625
TI  - The molecular interfacial structure and plasticizer migration behavior of "green"
      plasticized poly(vinyl chloride).
AB  - Tributyl acetyl citrate (TBAC), a widely-used "green" plasticizer, has been
      extensively applied in products for daily use. In this paper, a variety of
      analytical tools including sum frequency generation vibrational spectroscopy
      (SFG), coherent anti-Stokes Raman spectroscopy (CARS), contact angle goniometry
      (CA), and Fourier transform infrared spectroscopy (FTIR) were applied together to
      investigate the molecular structures of TBAC plasticized poly(vinyl chloride)
      (PVC) and the migration behavior of TBAC from PVC-TBAC mixtures into water. We
      comprehensively examine the effects of oxygen and argon plasma treatments on the
      surface structures of PVC-TBAC thin films containing various bulk percentages of
      plasticizers and the leaching behavior of TBAC into water. It was found that TBAC
      is a relatively stable PVC plasticizer compared to traditional non-covalent
      plasticizers but is also surface active. Oxygen plasma treatment increased the
      hydrophilicity of TBAC-PVC surfaces, but did not enhance TBAC leaching. However,
      argon plasma treatment greatly enhanced the leaching of TBAC molecules from PVC
      plastics to water. Based on our observations, we believe that oxygen plasma
      treatment could be applied to TBAC plasticized PVC products to enhance surface
      hydrophilicity for improving the biocompatibility and antibacterial properties of
      PVC products. The structural information obtained in this study will ultimately
      facilitate a molecular level understanding of plasticized polymers, aiding in the
      design of PVC materials with improved properties. 

PMID- 25579626
TI  - Nitrogen removal capacity of the river network in a high nitrogen loading region.
AB  - Denitrification is the primary process that regulates the removal of bioavailable
      nitrogen (N) from aquatic ecosystems. Quantifying the capacity of N removal from
      aquatic systems can provide a scientific basis for establishing the relationship
      between N reduction and water quality objectives, quantifying pollution
      contributions from different sources, as well as recommending control measures.
      The Lake Taihu region in China has a dense river network and heavy N pollution;
      however, the capacity for permanent N removal by the river network is unknown.
      Here, we concurrently examined environmental factors and net N2 flux from
      sediments of two rivers in the Lake Taihu region between July 2012 and May 2013,
      using membrane inlet mass spectrometry, and then established a regression model
      incorporating the highly correlated factors to predict the N removal capacity of
      the river network in the region. To test the applicability of the regression
      model, 21 additional rivers surrounding Lake Taihu were sampled between July and
      December 2013. The results suggested that water nitrate concentrations are still
      the primary controlling factor for net denitrification even in this high N
      loading river network, probably due to multicollinearity of other relevant
      factors, and thus can be used to predict N removal from aquatic systems. Our
      established model accounted for 78% of the variability in the measured net N2
      flux in these 21 rivers, and the total N removed through N2 production by the
      river network was estimated at 4 * 10(4) t yr(-1), accounting for about 43% of
      the total aquatic N load to the river system. Our results indicate that the
      average total N content in the river water discharged into Lake Taihu would be
      around 5.9 mg of N L(-1) in the current situation, far higher than the target
      concentration of 2 mg of N L(-1), given the total N load and the N removal
      capacity. Therefore, a much stronger effort is required to control the N
      pollution of the surface water in the region. 

PMID- 25579631
TI  - Sharp variations in the electronic properties of graphene deposited on the h-BN
      layer.
AB  - Investigation of the complex structure based on the graphene monolayer and the
      twisted BN monolayer was carried out. Sharp variations in the electronic
      structure during the hydrogen adsorption at low concentration were observed. Upon
      increasing the hydrogen concentration on the structure surfaces more impurity
      levels were observed due to the addition of the hydrogen atoms without any
      dependence on the position of hydrogen atoms on graphene and BN surfaces. An
      investigation of the dependence of the band gap on the hydrogen concentration on
      the Moire surface was made. Upon increasing the hydrogen concentration the value
      of the band gap increased up to 0.5 eV. 

PMID- 25579630
TI  - Analysis of chloramphenicol residues in the macroalgae Ulva lactuca through ultra
      high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC
      MS/MS).
AB  - Antibiotic use is a well-described practice to promote animal health whether for
      prevention or treatment. Nonetheless, it can also cause a number of potentially
      harmful effects that dictate the need to implement regulation to assure a
      reduction of hazards to the consumers and the environment. Chloramphenicol (CAP)
      is a broad-spectrum antibacterial excluded from use in animal food production but
      despite this, reports of illegal use still persist. More recently, awareness has
      risen that the surrounding natural ecosystems can potentially be contaminated by
      pharmaceuticals and the extent of their effects in non-target organisms is
      already under the scope of researchers. To face the demanding new challenges a
      methodology for the determination of CAP in the green macroalgae Ulva lactuca by
      ultra-high performance liquid chromatography coupled to tandem mass spectrometry
      (UHPLC-MS/MS) was developed, optimized and fully validated following the
      guidelines of the EC Decision 2002/657. 

PMID- 25579632
TI  - Ni(ii) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically,
      implicating nickel exposure as a contributing factor in pathologies related to
      antitrypsin deficiency.
AB  - Human alpha-1 antitrypsin (AAT) is an abundant serum protein present at a
      concentration of 1.0-1.5 g L(-1). AAT deficiency is a genetic disease that
      manifests with emphysema and liver cirrhosis due to the accumulation of a
      misfolded AAT mutant in hepatocytes. Lung AAT amount is inversely correlated with
      chronic obstructive pulmonary disease (COPD), a serious and often deadly
      condition, with increasing frequency in the aging population. Exposure to
      cigarette smoke and products of fossil fuel combustion aggravates AAT deficiency
      and COPD according to mechanisms that are not fully understood. Taking into
      account that these fumes contain particles that can release nickel to human
      airways and skin, we decided to investigate interactions of AAT with Ni(ii) ions
      within the paradigm of Ni(ii)-dependent peptide bond hydrolysis. We studied AAT
      protein derived from human blood using HPLC, SDS-PAGE, and mass spectrometry.
      These studies were aided by spectroscopic experiments on model peptides. As a
      result, we identified three hydrolysis sites in AAT. Two of them are present in
      the N-terminal part of the molecule next to each other (before Thr-13 and Ser-14
      residues) and effectively form one N-terminal cleavage site. The single C
      terminal cleavage site is located before Ser-285. The N-terminal hydrolysis was
      more efficient than the C-terminal one, but both abolished the ability of AAT to
      inhibit trypsin in an additive manner. Nickel ions bound to hydrolysis products
      demonstrated an ability to generate ROS. These results implicate Ni(ii) exposure
      as a contributing factor in AAT-related pathologies. 

PMID- 25579635
TI  - A spline-based tool to assess and visualize the calibration of multiclass risk
      predictions.
AB  - When validating risk models (or probabilistic classifiers), calibration is often
      overlooked. Calibration refers to the reliability of the predicted risks, i.e.
      whether the predicted risks correspond to observed probabilities. In medical
      applications this is important because treatment decisions often rely on the
      estimated risk of disease. The aim of this paper is to present generic tools to
      assess the calibration of multiclass risk models. We describe a calibration
      framework based on a vector spline multinomial logistic regression model. This
      framework can be used to generate calibration plots and calculate the estimated
      calibration index (ECI) to quantify lack of calibration. We illustrate these
      tools in relation to risk models used to characterize ovarian tumors. The outcome
      of the study is the surgical stage of the tumor when relevant and the final
      histological outcome, which is divided into five classes: benign, borderline
      malignant, stage I, stage II-IV, and secondary metastatic cancer. The 5909
      patients included in the study are randomly split into equally large training and
      test sets. We developed and tested models using the following algorithms:
      logistic regression, support vector machines, k nearest neighbors, random forest,
      naive Bayes and nearest shrunken centroids. Multiclass calibration plots are
      interesting as an approach to visualizing the reliability of predicted risks. The
      ECI is a convenient tool for comparing models, but is less informative and
      interpretable than calibration plots. In our case study, logistic regression and
      random forest showed the highest degree of calibration, and the naive Bayes the
      lowest. 

PMID- 25579636
TI  - Identification of Coronary Artery Calcification and Diagnosis of Coronary Artery
      Disease by Abdominal CT: A Resident Education Continuous Quality Improvement
      Project.
AB  - RATIONALE AND OBJECTIVES: Coronary artery calcium (CAC) scoring is an excellent
      imaging tool for subclinical atherosclerosis detection and risk stratification.
      We hypothesize that although CAC has been underreported in the past on computed
      tomography (CT) scans of the abdomen, specialized resident educational
      intervention can improve on this underreporting. MATERIALS AND METHODS: Beginning
      July 2009, a dedicated radiology resident cardiac imaging rotation and curriculum
      was initiated. A retrospective review of the first 500 abdominal CT reports from
      January 2009, 2011, and 2013 was performed including studies originally
      interpreted by a resident and primary attending physician interpretations. Each
      scan was reevaluated for presence or absence of CAC and coronary artery disease
      (CAD) by a cardiovascular CT expert reader. These data were then correlated to
      determine if the presence of CAC had been properly reported initially. The
      results of the three time periods were compared to assess for improved rates of
      CAC and CAD reporting after initiation of a resident cardiac imaging curriculum.
      RESULTS: Statistically significant improvements in the reporting of CAC and CAD
      on CT scans of the abdomen occurred after the initiation of formal resident
      cardiac imaging training which included two rotations (4 weeks each) of dedicated
      cardiac CT and cardiac magnetic resonance imaging interpretation during the
      resident's second, third, or fourth radiology training years. The improvement was
      persistent and increased over time, improving from 1% to 72% after 2 years and to
      90% after 4 years. CONCLUSIONS: This single-center retrospective analysis shows
      association between implementation of formal cardiac imaging training into
      radiology resident education and improved CAC detection and CAD reporting on
      abdominal CT scans.

PMID- 25579638
TI  - The reporting of prediction rules must be more predictable.

PMID- 25579637
TI  - Performance comparison of 1.5-T endorectal coil MRI with 3.0-T nonendorectal coil
      MRI in patients with prostate cancer.
AB  - RATIONALE AND OBJECTIVES: To compare prostate morphology, image quality, and
      diagnostic performance of 1.5-T endorectal coil magnetic resonance (MR) imaging
      (MRI) and 3.0-T nonendorectal coil MRI in patients with prostate cancer.
      MATERIALS AND METHODS: MR images obtained of 83 patients with prostate cancer
      using 1.5-T MRI systems with an endorectal coil were compared to images collected
      from 83 patients with a 3.0-T MRI system. Prostate diameters were measured, and
      image quality was evaluated by one American Board of Radiology (ABR)-certified
      radiologist (reader 1) and one ABR-certified diagnostic medical physicist (reader
      2). The likelihood of the presence of peripheral zone cancer in each sextant and
      local extent was rated and compared to histopathologic findings. RESULTS:
      Prostate anterior-posterior diameter measured by both readers was significantly
      shorter with 1.5-T endorectal MRI than with 3.0-T MRI. The overall image quality
      score difference was significant only for reader 1. Both readers found that the
      two MRI systems provided a similar diagnostic accuracy in cancer localization,
      extraprostatic extension, and seminal vesicle involvement. CONCLUSIONS:
      Nonendorectal coil 3.0-T MRI provides prostate images that are natural in shape
      and that have comparable image quality to those obtained at 1.5 T with an
      endorectal coil, but not superior diagnostic performance. These findings suggest
      an opportunity exists for improving technical aspects of the 3.0-T prostate MRI.

PMID- 25579639
TI  - Regression discontinuity designs are underutilized in medicine, epidemiology, and
      public health: a review of current and best practice.
AB  - OBJECTIVES: Regression discontinuity (RD) designs allow for rigorous causal
      inference when patients receive a treatment based on scoring above or below a
      cutoff point on a continuously measured variable. We provide an introduction to
      the theory of RD and a systematic review and assessment of the RD literature in
      medicine, epidemiology, and public health. STUDY DESIGN AND SETTING: We review
      the necessary conditions for valid RD results, provide a practical guide to RD
      implementation, compare RD to other methodologies, and conduct a systematic
      review of the RD literature in PubMed. RESULTS: We describe five key elements of
      analysis all RD studies should report, including tests of validity conditions and
      robustness checks. Thirty two empirical RD studies in PubMed met our selection
      criteria. Most of the 32 RD articles analyzed the effectiveness of social
      policies or mental health interventions, with only two evaluating clinical
      interventions to improve physical health. Seven out of the 32 studies reported on
      all the five key elements. CONCLUSION: Increased use of RD provides an exciting
      opportunity for obtaining unbiased causal effect estimates when experiments are
      not feasible or when we want to evaluate programs under "real-life" conditions.
      Although treatment eligibility in medicine, epidemiology, and public health is
      commonly determined by threshold rules, use of RD in these fields has been very
      limited until now.

PMID- 25579640
TI  - Transparent reporting of a multivariable prediction model for Individual
      Prognosis or Diagnosis (TRIPOD): the TRIPOD statement.
AB  - Prediction models are developed to aid health care providers in estimating the
      probability or risk that a specific disease or condition is present (diagnostic
      models) or that a specific event will occur in the future (prognostic models), to
      inform their decision making. However, the overwhelming evidence shows that the
      quality of reporting of prediction model studies is poor. Only with full and
      clear reporting of information on all aspects of a prediction model can risk of
      bias and potential usefulness of prediction models be adequately assessed. The
      Transparent Reporting of a multivariable prediction model for Individual
      Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for
      the reporting of studies developing, validating, or updating a prediction model,
      whether for diagnostic or prognostic purposes. This article describes how the
      TRIPOD Statement was developed. An extensive list of items based on a review of
      the literature was created, which was reduced after a Web-based survey and
      revised during a 3-day meeting in June 2011 with methodologists, health care
      professionals, and journal editors. The list was refined during several meetings
      of the steering group and in e-mail discussions with the wider group of TRIPOD
      contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed
      essential for transparent reporting of a prediction model study. The TRIPOD
      Statement aims to improve the transparency of the reporting of a prediction model
      study regardless of the study methods used. The TRIPOD Statement is best used in
      conjunction with the TRIPOD explanation and elaboration document. To aid the
      editorial process and readers of prediction model studies, it is recommended that
      authors include a completed checklist in their submission (also available at
      www.tripod-statement.org). 

PMID- 25579641
TI  - Complications and visual outcomes after secondary intraocular lens implantation
      in children.
AB  - PURPOSE: To evaluate safety and visual outcomes in surgically aphakic children
      undergoing secondary intraocular lens (IOL) implantation. DESIGN: Retrospective,
      consecutive, interventional case series. METHODS: One hundred seventy-four eyes
      of 104 children (70 bilateral, 34 unilateral) who underwent secondary IOL
      implantation for aphakia after congenital cataract surgery at L. V. Prasad Eye
      Institute, Hyderabad, India, were analyzed. A minimum of 3 months of follow-up
      after surgery was required for inclusion in the study. Eyes with aphakia after
      surgery for traumatic cataracts and other associated ocular comorbidities were
      excluded. Main outcome measures were intraoperative and postoperative
      complications and visual outcome at the last follow-up. RESULTS: Mean age at
      secondary IOL implantation was 6.08 +/- 3.75 years. The mean follow-up was 25.7
      +/- 24.9 months. Mean best-corrected visual acuity improved from 1.08 +/- 0.65 in
      aphakic children to 0.55 +/- 0.51 logarithm of the minimal angle of resolution in
      pseudophakic children at last follow-up (P < .0001). Overall, 51 eyes (35%)
      attained a final best-corrected visual acuity of 20/40 (0.3 logarithm of the
      minimal angle of resolution) or better, whereas only 2 eyes (8.7%) attained a
      final best-corrected visual acuity of 20/40 (0.3 logarithm of the minimal angle
      of resolution) or better in children who underwent secondary IOL implantation for
      unilateral aphakia. The most common postoperative complications were secondary
      membrane formation (17 eyes; 9.77%), optic capture (15 eyes; 8.6%), IOL
      decentration (9 eyes; 5.17%), and secondary glaucoma (11 eyes; 5%). CONCLUSIONS:
      Secondary sulcus IOL implantation in children is a relatively safe procedure and
      leads to favorable visual postoperative outcomes.

PMID- 25579642
TI  - Retinal and choroidal changes and visual outcome in central retinal artery
      occlusion: an optical coherence tomography study.
AB  - PURPOSE: To investigate the retinal and choroidal changes using spectral-domain
      optical coherence tomography (SD OCT) and to identify factors associated with
      visual outcome in eyes with central retinal artery occlusion (CRAO). DESIGN:
      Retrospective, observational case series. METHODS: setting: Institutional.
      PATIENTS: A total of 134 eyes diagnosed with acute (symptom onset <= 7 days)
      nonarteritic CRAO examined with SD OCT at baseline and follow-up visits.
      OBSERVATIONS: Based on funduscopic and angiographic findings, CRAO was
      categorized into 3 stages: incomplete, subtotal, and total. Abnormal morphologic
      features were evaluated from SD OCT images. Central macular thickness (CMT),
      inner and outer retinal thicknesses, and subfoveal choroidal thickness (SFCT)
      were measured. The clinical and SD OCT features were correlated with the final
      best-corrected visual acuities (BCVA). MAIN OUTCOME MEASURES: Retinal and
      choroidal thickness and BCVA. RESULTS: Features of SD OCT at the initial
      presentation included inner and outer retinal thickening. At baseline, the
      frequency of inner and outer retinal thickening and macular edema (CMT > 300 MUm)
      differed significantly among CRAO stages (all P < .05). SFCT in eyes with total
      CRAO was significantly thinner compared with that of the contralateral eyes (P =
      .009). A higher CRAO stage was associated significantly with macular edema at
      baseline (P < .001) and retinal thinning at the final visit (P = .010). Baseline
      CMT was correlated significantly with final BCVA (P < .001). Multivariate
      logistic regression analyses revealed that severe vision loss (BCVA < 20/200) was
      associated significantly with CRAO stage (P < .001) and baseline CMT (P = .005).
      CONCLUSIONS: CRAO resulted in inner and outer retinal thickening in the acute
      stages and subsequent atrophic changes in the inner and outer retina. SD OCT may
      be a useful noninvasive imaging tool for diagnosis, staging, and prognosis of
      CRAO.

PMID- 25579644
TI  - Fourier-domain optical coherence tomography imaging in corneal epithelial
      basement membrane dystrophy: a structural analysis.
AB  - PURPOSE: To investigate the features of corneal epithelial basement membrane
      dystrophy using spectral-domain optical coherence tomography (SD OCT) and to
      examine the reliability of SD OCT in distinguishing epithelial basement membrane
      dystrophy from the normal cornea. DESIGN: Diagnostic test study. METHODS: Forty
      five individuals with epithelial basement membrane dystrophy and 45 age- and sex
      matched controls with normal corneas were examined, and SD OCT scans of their
      corneas were performed. In vivo confocal microscopy was performed to confirm or
      rule out the diagnosis of epithelial basement membrane dystrophy. The structural
      corneal changes occurring in eyes with epithelial basement membrane dystrophy
      based on SD OCT findings were described. RESULTS: Epithelial abnormalities were
      observed in 86 of 87 eyes with epithelial basement membrane dystrophy (45
      patients) on SD OCT scans. The 2 main features were the presence of an irregular
      and thickened epithelial basement membrane duplicating or insinuating into the
      corneal epithelium layer, or both, and the presence of hyperreflective dots. In
      some cases, we detected hyporeflective spaces between the corneal epithelial
      layer and the Bowman layer similar to a corneal epithelial detachment. This
      corneal epithelial detachment sometimes was associated with a cleavage with a
      stair-step appearance within the corneal epithelial layer. We found a perfect
      correlation between in vivo confocal microscopy and SD OCT findings in the
      diagnosis of epithelial basement membrane dystrophy (kappa = 0.98). CONCLUSIONS:
      SD OCT provides an accurate assessment of the structural changes occurring in
      eyes with epithelial basement membrane dystrophy. These changes, visible on SD
      OCT scans, are easily detectable and permit an accurate diagnosis, especially in
      patients with no biomicroscopically visible corneal changes.

PMID- 25579643
TI  - Extreme thinning or loss of inner neural retina along the staphyloma edge in eyes
      with pathologic myopia.
AB  - PURPOSE: To investigate the morphologic changes along the edge of posterior
      staphyloma in highly myopic eyes with patchy chorioretinal atrophy and to
      identify the relationship between retinal thinning and the visual field (VF)
      defects found in these eyes. DESIGN: Retrospective, observational case series.
      METHODS: Twenty eyes (17 patients) with pathologic myopia (myopic refractive
      error >= 8 diopters or an axial length >= 26.5 mm) and patchy atrophy along the
      staphyloma edge were analyzed retrospectively. The VFs were obtained by Goldmann
      kinetic perimetry. RESULTS: In the area of patchy atrophy, the inner retinal
      tissue was very thin or completely absent. Any remnants of the retinal tissue
      appeared to be adherent to the layer of large choroidal vessels or to the sclera.
      The mean thickness of the retina at its thinnest point in the area was 51.6 +/-
      29.0 MUm in 20 eyes. The retina was thinner than 50 MUm at its thinnest point in
      12 (60.0%) of the 20 eyes, and the mean retinal thickness at its thinnest point
      in these 12 eyes was 32.1 +/- 16.0 MUm (range, 4 to 49 MUm). Nineteen eyes (VF of
      1 eye was not determined) had very similar VF findings by Goldmann perimetry,
      that is, a defect of the sector corresponding to the course of retinal nerve
      fiber over the patchy atrophy. CONCLUSIONS: The results show that the thickness
      of not only the outer retina, but also of most of the inner retina, including the
      nerve fiber layer, is significantly thinner at the staphyloma edge. Such damage
      to the inner retina along the staphyloma edge causes the VF defects in highly
      myopic eyes.

PMID- 25579645
TI  - Gene expression profiling in the lungs of phenylhydrazine-treated rats: the
      contribution of pro-inflammatory response and endothelial dysfunction to acute
      thrombosis.
AB  - Pulmonary thrombosis is a life-threatening disorder caused by various risk
      factors. We previously reported that phenylhydrazine (PHZ) induces acute
      thrombosis in the rat lung, with regional stasis in the alveolar capillaries as a
      trigger, and subsequent hemostatic disruption is involved as an accelerator in
      the pathogenesis of this condition. In this study, we examined the other possible
      pathogenesis, particularly endothelial dysfunction in the lungs of PHZ-treated
      rats using gene expression profiling. Male Sprague Dawley rats were administered
      PHZ at a dose of 40mg/kg/day daily for up to 3 days (n=4). At 24h after the last
      administration (i.e. on days 1, 2 or 3), animals were euthanized and lung tissues
      were subjected to histopathological and microarray analyses. In the alveolar
      capillaries in PHZ-treated rats, slight congestion was observed on day 1, which
      was exacerbated with repeated administration, and multifocal thrombi were formed
      on day 3. A change in the level of expression of thrombosis-related genes in the
      vascular endothelial cell was mainly observed on day 3; anticoagulant factors
      such as tissue factor pathway inhibitor (lipoprotein-associated coagulation
      inhibitor) and thrombomodulin were down-regulated; coagulant factors such as
      coagulation factor III (thromboplastin, tissue factor) and adhesion molecules
      such as selectin E were up-regulated. The gene ontology categories most
      significantly affected by PHZ were inflammation/immune response (from days 1 to
      3) and blood coagulation and hemostasis (days 2 and 3). These findings suggest
      that PHZ caused dysfunction of endothelial cells, which resulted in a
      hypercoagulable state and it would act as one of the contributors of acute
      pulmonary thrombosis. In addition, the pro-inflammatory condition observed at the
      early stage of treatment was considered to play an important part in the
      development of thrombosis due to endothelial dysfunction.

PMID- 25579646
TI  - Endocrine activity of alternatives to BPA found in thermal paper in Switzerland.
AB  - Alternatives to bisphenol A (BPA) are more and more used in thermal paper
      receipts. To get an overview of the situation in Switzerland, 124 thermal paper
      receipts were collected and analyzed. Whereas BPA was detected in most samples
      (n=100), some alternatives, namely bisphenol S (BPS), Pergafast(r) 201 and D-8
      have been found in 4, 11 and 9 samples respectively. As no or few data on their
      endocrine activity are available, these chemicals and bisphenol F (BPF) were
      tested in vitro using the H295R steroidogenesis assay. 17beta-Estradiol
      production was induced by BPA and BPF, whereas free testosterone production was
      inhibited by BPA and BPS. Both non-bisphenol substances did not show significant
      effects. The binding affinity to 16 proteins and the toxicological potential (TP)
      were further calculated in silico using VirtualToxLabTM. TP values lay between
      0.269 and 0.476 and the main target was the estrogen receptor beta (84.4 nM to
      1.33 MUM). A substitution of BPA by BPF and BPS should be thus considered with
      caution, since they exhibit almost a similar endocrine activity as BPA. D-8 and
      Pergafast(r) 201 could be alternatives to replace BPA, however further analyses
      are needed to better characterize their effects on the hormonal system.

PMID- 25579651
TI  - Priapism after tumor necrosis factor alpha inhibitor use.
AB  - We present a possible important association of tumor necrosis factor-alpha
      inhibition (TNFa-i) and erectile function in a male patient with rheumatoid
      arthritis (RA). Long-standing, untreated RA may result in significant physical
      limitation and disability, however often overlooked is the association between RA
      and erectile and sexual dysfunction. Ischemic priapism is currently unrecognized
      as an adverse reaction associated with TNFa-i use and there have been no reported
      cases with adalimumab. Our patient, a 58-year-old Hispanic man, with sero
      positive, erosive RA developed persistent priapism (17 days) despite multiple
      urologic interventions after initial adalimumab 40 mg administration. TNFa has
      recently been implicated as a potential factor in erectile dysfunction through
      its role in vascular reactivity. Excess TNFa, from active RA, may perturb
      intracavernosal smooth muscle and endothelial cell function; theoretically, TNFa
      inhibition may then causes excess local nitric oxide production and subsequent
      priapism. The potential role of TNFa-i in ED and risk for priapism is an
      important area for future study. 

PMID- 25579647
TI  - TALEN-Mediated Gene Disruption on Y Chromosome Reveals Critical Role of EIF2S3Y
      in Mouse Spermatogenesis.
AB  - The Y chromosome plays a critical role in spermatogenesis. Formerly, it had been
      difficult to generate knockout mice with specific Y chromosome mutations using
      conventional gene-targeting strategies. Recently, a transcription activator-like
      effector nuclease (TALEN) was successfully used for editing a mouse Y chromosome
      linked gene. Here, we report the generation of a mouse model with a mutation in
      EIF2S3Y, a Y chromosome-linked gene, and analysis of its phenotype. The mouse
      carrying a targeted mutation of EIF2S3Y was infertile and had hypoplastic testes.
      Histological and electron microscopic analyses showed that differentiation of
      spermatogonia was arrested at the stage of spermatogonial stem cells
      (undifferentiated spermatogonia) and that the progression of spermatogenesis was
      interrupted, resulting in azoospermia. Using TALEN, we verified that EIF2S3Y
      performs a key function in differentiation of spermatogonial stem cells.

PMID- 25579652
TI  - Discovery of two new classes of potent monoamine oxidase-B inhibitors by tricky
      chemistry.
AB  - The discovery of potent and selective monoamine oxidase-B inhibitors for the
      management of neurodegenerative diseases such as Alzheimer's and Parkinson's
      diseases is still a challenging endeavor. Herein, we report the discovery of two
      new classes of potent and selective MAO-B inhibitors based on chromane-2,4-dione
      and chromone-3-carboxamide scaffolds. 

PMID- 25579653
TI  - Prevalence of self-reported myocardial infarction in Sami and non-Sami
      populations: the SAMINOR study.
AB  - OBJECTIVE: Measure the prevalence of self-reported myocardial infarction (SMI) in
      Sami and non-Sami populations in rural areas of Norway, and explore whether
      possible ethnic differences could be explained by established cardiovascular risk
      factors. DESIGN: Cross-sectional population-based study. METHODS: A health survey
      was conducted in 2003-2004 in areas with Sami and non-Sami populations (SAMINOR).
      The response rate was 60.9%. Information concerning lifestyle was collected by 2
      self-administrated questionnaires, and clinical examinations provided
      anthropometric measurements, and data on blood pressure and lipid levels.
      RESULTS: The total number for the subsequent analysis was 15,206 men and women
      aged 36-79 years (born 1925-1968). Sex-specific analyses revealed no ethnic
      difference in SMI. In terms of the most important risk factors such as smoking,
      blood pressure, and lipid levels, no or only trivial ethnic differences were
      found in both women and men. CONCLUSION: In this study, we found no difference in
      SMI between Sami and non-Sami in rural areas in Norway. The similar risk profile
      is the most plausible explanation; similar living conditions and close
      interaction between the ethnic groups may explain this.

PMID- 25579654
TI  - Molecular structure, vibrational analysis (FT-IR, FT-Raman), NMR, UV, NBO and
      HOMO-LUMO analysis of N,N-Diphenyl Formamide based on DFT calculations.
AB  - In this work, the vibrational spectral analysis is carried out by using Raman and
      infrared spectroscopy in the range 4000-400 cm(-1) and 4000-50 cm(-1)
      respectively for N,N-Diphenyl Formamide (DPF) molecule. The optimized molecular
      structures, vibrational frequencies and corresponding vibrational assignments,
      nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-VIS) spectra of the
      title molecule are evaluated using density functional theory (DFT) with standard
      B3LYP/6-31G(d,p) basis set. The harmonic vibrational frequencies are calculated
      and the scaled values have been compared with experimental FT-IR and FT-Raman
      spectra. The observed and calculated frequencies are found to be in good
      agreement. The stability of the molecule arising from hyper conjugative
      interactions and the charge delocalization has been analyzed using natural bond
      (NBO) analysis. The possible electronic transitions are determined by HOMO-LUMO
      orbital shapes and their energies. Thermodynamic properties (heat capacity,
      entropy and enthalpy) and the first hyperpolarizability of the title compound are
      calculated. The Mulliken charges and electric dipole moment of the molecule are
      computed using DFT calculations. The (1)H and (13)C nuclear magnetic resonance
      (NMR) chemical shift of the molecules are calculated by the gauge independent
      atomic orbital (GIAO) method and compared with experimental results.

PMID- 25579655
TI  - Synthesis and structure of interaction products of quinoline-2(1H)-thione with
      molecular iodine.
AB  - The behavior of quinoline-2(1H)-thione, which is a potential antithyroid drug
      toward molecular iodine, was investigated. The ability of quinoline-2(1H)-thione
      to form the outer-sphere charge-transfer complex C9H7NS.I2 with iodine molecular
      in dilute chloroform solution has been studied by UV-vis spectroscopy
      (lgbeta=3.85). The crystal structure of the new salt 2-(quinoline-2
      yldisulfanyl)quinolinium triiodide - product of irreversible oxidation of
      quinoline-2(1H)-thione was determined by X-ray diffraction. The 2-(quinoline-2
      yldisulfanyl)quinolinium cations form dimers through pi-pi-stacking interaction
      between quinoline rings. Strong intramolecular interactions are observed between
      iodine - sulfur atoms and iodine - hydrogen atoms with shortened contacts (less
      of sum of van der Waals contacts). It is noteworthy that two perfectly
      centrosymmetrical anions I3(-) form a very short contact I(3)?I(3') 3.7550(5) so
      we can state the formation of the dianion I(6)(2-). Therefore the formation and
      topology of polyiodide species depend on the characteristics, such as shape, size
      and charge, etc., of the counter cation, 2-(quinoline-2-yldisulfanyl)quinolinium,
      which is considered as templating agent.

PMID- 25579656
TI  - The spectroscopic (FT-IR, UV-vis), Fukui function, NLO, NBO, NPA and tautomerism
      effect analysis of (E)-2-[(2-hydroxy-6-methoxybenzylidene)amino]benzonitrile.
AB  - A new o-hydroxy Schiff base, (E)-2-[(2-hydroxy-6
      methoxybenzylidene)amino]benzonitrile was isolated and investigated by
      experimental and theoretical methodologies. The solid state molecular structure
      was determined by X-ray diffraction method. The vibrational spectral analysis was
      carried out by using FT-IR spectroscopy in the range of 4000-400cm(-)(1).
      Theoretical calculations were performed by density functional theory (DFT) method
      using 6-31G(d,p) basis set. The results of the calculations were applied to
      simulated spectra of the title compound, which show excellent agreement with
      observed spectra. The UV-vis spectrum of the compound was recorded in the region
      200-800 nm in several solvents and electronic properties such as excitation
      energies, and wavelengths were calculated by TD-DFT/B3LYP method. The most
      prominent transitions were corresponds to pi->pi*. Hybrid density functional
      theory (DFT) was used to investigate the enol-imine and keto-amine tautomers of
      titled compound. The titled compound showed the preference of enol form, as
      supported by X-ray and spectroscopic analysis results. The geometric and
      molecular properties were compaired for both enol-imine and keto-amine forms.
      Additionally, geometry optimizations in solvent media were performed with the
      same level of theory by the integral equation formalism polarizable continuum
      (IEF-PCM). Stability of the molecule arises from hyperconjugative interactions,
      charge delocalization and intramolecular hydrogen bond has been analyzed using
      natural bond orbital (NBO) analysis. Mulliken population method and natural
      population analysis (NPA) have been studied. Also, condensed Fukui function and
      relative nucleophilicity indices calculated from charges obtained with orbital
      charge calculation methods (NPA). Molecular electrostatic potential (MEP) and non
      linear optical (NLO) properties are also examined.

PMID- 25579657
TI  - Intercontinental long-distance dispersal of Canellaceae from the New to the Old
      World revealed by a nuclear single copy gene and chloroplast loci.
AB  - Canellales, a clade consisting of Winteraceae and Canellaceae, represent the
      smallest order of magnoliid angiosperms. The clade shows a broad distribution
      throughout the Southern Hemisphere, across a diverse range of dry to wet tropical
      forests. In contrast to their sister-group, Winteraceae, the phylogenetic
      relations and biogeography within Canellaceae remain poorly studied. Here we
      present the phylogenetic relationships of all currently recognized genera of
      Canellales with a special focus on the Old World Canellaceae using a combined
      dataset consisting of the chloroplast trnK-matK-trnK-psbA and the nuclear single
      copy gene mag1 (Maigo 1). Within Canellaceae we found high statistical support
      for the monophyly of Warburgia and Cinnamosma. However, we also found
      relationships that differ from previous studies. Cinnamodendron splitted into two
      clades, a South American clade and a second clade confined to the Antilles and
      adjacent areas. Cinnamodendron from the Antilles, as well as Capsicodendron,
      South American Cinnamodendron and Pleodendron were not monophyletic.
      Consequently, Capsicodendron should be included in the South American
      Cinnamodendron clade and the genus Pleodendron merged with the Cinnamodendron
      clade from the Antilles. We also found that Warburgia (restricted to mainland
      eastern Africa) together with the South American Cinnamodendron and
      Capsicodendron are sister to the Malagasy genus Cinnamosma. In addition to the
      unexpected geographical relationships, both biogeographic and molecular clock
      analyses suggest vicariance, extinction, and at least one intercontinental long
      distance-dispersal event. Our dating result contrasts previous work on
      Winteraceae. Diversification of Winteraceae took place in the Paleocene,
      predating the Canellaceae diversification by 13 MA in the Eocene. The
      phylogenetic relationships for Canellaceae supported here offer a solid framework
      for a future taxonomic revision of the Canellaceae. 

PMID- 25579658
TI  - Modeling of the putative distribution of the arbovirus vector Ochlerotatus
      japonicus japonicus (Diptera: Culicidae) in Germany.
AB  - Today, international travel and global freight transportation are increasing and
      have a direct influence on the introduction and establishment of non-native
      mosquito species as well as on the spread of arthropod (mosquito)-borne diseases
      inside Europe. One of the mosquito species that has become invasive in many areas
      is the Asian rock pool or bush mosquito Ochlerotatus japonicus japonicus
      (synonyms: Aedes japonicus japonicus or Hulecoeteomyia japonica japonica). This
      species was detected in Germany in 2008 for the first time. Until today, three
      different Oc. j. japonicus populations have been documented. Laboratory studies
      have shown that Oc. j. japonicus can act as a vector for a variety of disease
      agents. Thus, the knowledge on its current distribution is essential for
      different measurements. In the present study, ecological niche models were used
      to estimate the potential distribution of Oc. j. japonicus in Germany. The aim
      was to detect areas within Germany that could potentially function as habitats
      for this species. According to our model, areas in western, southern, and central
      Germany offer suitable conditions for the mosquito and may therefore be at risk
      for an invasion of the species. We strongly suggest that those areas should be
      monitored more intensively in the future. For this purpose, it would also be
      essential to search for possible dispersal routes as well as for natural
      barriers. 

PMID- 25579659
TI  - Effects of grafting with pumpkin rootstock on carbohydrate metabolism in cucumber
      seedlings under Ca(NO3)2 stress.
AB  - This study investigated the effects of grafting on the carbohydrate status and
      the enzymes of carbohydrate metabolism in self-grafted and grafted cucumber
      seedlings using the salt-tolerant pumpkin rootstock 'Qingzhen 1' (Cucurbita
      maxima * Cucurbita moschata) under 80 mM Ca(NO3)2 stress for 6 d. The growth of
      self-grafted seedlings was significantly inhibited after the treatment of
      Ca(NO3)2 stress, whereas the inhibition of growth was alleviated in pumpkin
      rootstock-grafted seedlings. Ca(NO3)2 stress increased the contents of the total
      soluble sugar, sucrose and fructose, but decreased the starch content in
      rootstock-grafted leaves. However, compared with self-grafted plants, rootstock
      grafted seedlings were observed with a higher content of sucrose and total
      soluble sugar (TSS) under salt stress. Rootstock-grafted seedlings exhibited
      higher activities of acid invertase (AI), neutral invertase (NI) and phosphate
      sucrose synthase (SPS) of sucrose metabolism in leaves than that of self-grafted
      seedlings under salinity. Moreover, the activities of fructokinase (FK),
      hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) of glycolysis
      were maintained at a higher level in leaves of rootstock-grafted seedlings after
      Ca(NO3)2 stress. Additionally, rootstock-grafting decrease the high percentage
      enhancement of key enzymes gene expression in glycolysis in the scion leaves of
      cucumber seedlings induced by salt stress. These results suggest that the
      rootstock-grafting improved salt tolerance, which might play a role in elevated
      sucrose metabolism and a glycolytic pathway regulated by the pumpkin rootstock.

PMID- 25579660
TI  - Deterioration mechanisms in air-dry pea seeds during early aging.
AB  - The deteriorative reactions underlying seed aging, namely, lipid peroxidation and
      non-enzymatic carbohydrate hydrolysis, were studied in pea seeds differing in
      quality. Aging air-dry seeds were subdivided to three fractions using the
      application to individual seeds of room temperature phosphorescence. These
      fractions were strong seeds (fraction I) producing normal seedlings, weak seeds
      (fraction II) producing mainly abnormal seedlings, and dead seeds (fraction III).
      Enzymatic processes cannot operate in dry seeds due to the absence of free water,
      and thus an analytical method was needed that does not require the addition of
      water. The content of lipid peroxidation products was similar in both strong and
      weak seeds; this excluded the possibility that lipid peroxidation induced the
      transition of strong to weak seeds during early aging. Lipid peroxidation was
      activated only in dying seeds. However, glucose content in weak seeds was much
      higher than in strong seeds, suggestive of non-enzymatic hydrolysis of
      carbohydrates, probably of oligosaccharides, which utilized bound water in air
      dry seeds. This process resulted in lowered water content in weak seeds.
      Therefore, associated with deterioration of air-dry seeds during early aging is
      the non-enzymatic hydrolysis of carbohydrates, whereas lipid peroxidation is not
      the decisive event. 

PMID- 25579661
TI  - Changes in H-reflex and V-waves following spinal manipulation.
AB  - This study investigates whether spinal manipulation leads to neural plastic
      changes involving cortical drive and the H-reflex pathway. Soleus evoked V-wave,
      H-reflex, and M-wave recruitment curves and maximum voluntary contraction (MVC)
      in surface electromyography (SEMG) signals of the plantar flexors were recorded
      from ten subjects before and after manipulation or control intervention.
      Dependent measures were compared with 2-way ANOVA and Tukey's HSD as post hoc
      test, p was set at 0.05. Spinal manipulation resulted in increased MVC (measured
      with SEMG) by 59.5 +/- 103.4 % (p = 0.03) and force by 16.05 +/- 6.16 4 % (p =
      0.0002), increased V/M max ratio by 44.97 +/- 36.02 % (p = 0.006), and reduced H
      reflex threshold (p = 0.018). Following the control intervention, there was a
      decrease in MVC (measured with SEMG) by 13.31 +/- 7.27 % (p = 0.001) and force by
      11.35 +/- 9.99 % (p = 0.030), decreased V/M max ratio (23.45 +/- 17.65 %; p =
      0.03) and a decrease in the median frequency of the power spectrum (p = 0.04) of
      the SEMG during MVC. The H-reflex pathway is involved in the neural plastic
      changes that occur following spinal manipulation. The improvements in MVC
      following spinal manipulation are likely attributed to increased descending drive
      and/or modulation in afferents. Spinal manipulation appears to prevent fatigue
      developed during maximal contractions. Spinal manipulation appears to alter the
      net excitability of the low-threshold motor units, increase cortical drive, and
      prevent fatigue.

PMID- 25579662
TI  - Upper limb performance and the structuring of joint movement in teenagers with
      cerebral palsy: the reciprocal role of task demands and action capabilities.
AB  - Individuals with unilateral cerebral palsy (CP) demonstrate reduced performance
      in upper limb tasks compared to typically developing (TD) peers. We examined
      whether task conditions modify differences between teenagers with and without CP
      during a reciprocal aiming task. Twenty teenagers (nine CP and 11 TD) moved a
      pointer between two targets as fast as possible without missing a target. Task
      conditions were manipulated by changing the targets' size, by modifying the
      inertial properties of the pointer and by varying the upper limb used to perform
      the task (preferred/non-affected and non-preferred/affected upper limbs). While
      compared to TD peers, CP teenagers exhibited lower performance (longer movement
      times). Such differences were attenuated when the task was performed with the
      preferred upper limb and when accuracy requirements were less stringent. CP
      teenagers were not differentially affected by the pointer inertia manipulation.
      Task conditions not only affected performance but also joint kinematics. CP
      teenagers revealed less movement at the elbow and more movement at the shoulder
      when performing the task with their less skilled upper limb. However, both CP and
      TD teenagers demonstrated a larger contribution of trunk movement when facing
      more challenging task conditions. The overall pattern of results indicated that
      the joint kinematics employed by individuals with unilateral CP constituted
      adaptive responses to task requirements. Thus, the explanation of the effects of
      unilateral CP on upper limb behavior needs to go beyond a context-indifferent
      manifestation of the brain injury to include the interaction between task demands
      and action capabilities.

PMID- 25579663
TI  - Activation patterns of different brain areas during incremental exercise measured
      by near-infrared spectroscopy.
AB  - Recent studies postulated that increased oxygenation of the prefrontal cortex
      (PFC) during elevating exercise intensities reflects a specific activation of
      this region. Furthermore, the drop in PFC oxygenation often measured shortly
      before exhaustion is interpreted as a main factor limiting exercise.
      Nevertheless, a limitation of these studies is that they often measured NIRS only
      in the PFC. Within this study, we hypothesized that these findings are not region
      specific but rather result from systemic blood redistribution to the working
      skeletal muscle. NIRS was measured in three different brain regions and the
      working skeletal muscle during incremental cycling till exhaustion in nine
      healthy men. Oxygenated hemoglobin of the PFC increased from low to submaximal
      intensities and leveled off at maximal intensities. There was no drop in PFC
      oxygenation before exercise abortion. Interestingly, the occipital cortex was
      unaffected during exercise, while the motor cortex showed an increasing
      deoxygenation with elevating exercise intensities, just as observed in the
      skeletal muscle. In conclusion, this study does not support the notion that PFC
      deoxygenation is involved in the limitation of maximum exercise capacity. Against
      the hypothesis, the NIRS signals of the other cortices differed clearly,
      indicating that the previously reported findings indeed represent region-specific
      activations.

PMID- 25579664
TI  - Selection of biologics for patients with metastatic colorectal cancer: the role
      of predictive markers.
AB  - With the advent of biologics, the survival and quality of life of patients
      diagnosed with metastatic colorectal cancer (mCRC) has improved. These agents
      include anti-VEGF agents (bevacizumab/aflibercept), anti-EGFR antibodies
      (panitumumab/cetuximab) and regorafenib (an oral multi-kinase inhibitor). With
      the use of the novel therapeutics, there was a notable increase in the median
      survival of patients with mCRC; however, there are still several unmet needs with
      the use of novel therapeutics in mCRC. The focus of this editorial is to
      highlight some of these issues alongside results of some of the important
      clinical trials and other studies presented at the American Society of Clinical
      Oncology meeting last year. 

PMID- 25579665
TI  - RASSF5A, a candidate tumor suppressor, is epigenetically inactivated in
      esophageal squamous cell carcinoma.
AB  - As a result of alternative splicing and differential promoter usage, RASSF5
      exists in at least three isoforms (RASSF5A-RASSF5C), which may play different
      roles in tumorigenesis. The present study was to detect the role of RASSF5A, B
      and C in esophageal squamous cell carcinoma (ESCC) and clarify the critical CpG
      sites of RASSF5A, in order to clarify more information on the role of RASSF5 with
      regard to the pathogenesis of ESCC. Frequent silencing of RASSF5A but not RASSF5B
      and RASSF5C were found in esophageal cancer cell lines and the silencing of
      RASSF5A may be reversed by 5-Aza-dC or TSA treatment. The aberrant CpG island 1
      methylation of RASSF5A induces silencing of its expression in TE13 cell line.
      Decreased mRNA and protein expression of RASSF5A was observed in ESCC tumor
      tissues and was associated with RASSF5A CpG island 1 methylation status. Unlike
      RASSF5A, expression variation of RASSF5B and RASSF5C was not found in ESCC
      tissues. Aberrant promoter methylation of RASSF5C was also not found in ESCC.
      RASSF5A methylation and protein expression were independently associated with
      ESCC patients' survival. These data indicated that the inactivation of RASSF5A
      through CpG island 1 methylation may play an important role in ESCC
      carcinogenesis, RASSF5A may be a functional tumor suppressor and may serve as a
      prognostic biomarker for ESCC. 

PMID- 25579667
TI  - The Ten Essential Shared Capabilities: reflections on education in values based
      practice: a qualitative study.
AB  - BACKGROUND: This paper presents the findings of a study exploring the impact of a
      values-based training initiative on the practice of mental health workers. This
      work is set within the context of increasing attention on the values of nurses
      and other health care workers as a response to national reports on care failure
      and negative media attention. OBJECTIVE: To examine written response feedback
      from participants on a national training programme for values-based practice
      (VBP) in order to examine any intention to change practice. DESIGN: A national
      evaluation using quantitative and qualitative methodologies was conducted to
      gather data on reflections and self-report impact of the Ten Essential Shared
      Capabilities' training programme. SETTING: The training was delivered in a range
      of hospital, community and third sector training programmes across eight regions
      in England. PARTICIPANTS: The participants were predominantly nurses but all
      sectors in the mental health community including service users as co-facilitators
      and participants were represented. METHODS: This study presents the qualitative
      findings from a cross-sectional survey. Using NVIVO 10 software, data were
      analysed using the framework method of qualitative analysis. RESULTS: Four
      principal themes emerged from the data'Thinking differently''Changes to
      practice''Creating an effective learning environment and skills for practice
      development' and 'Increasing self-awareness'. CONCLUSIONS: The quality and safety
      drive in the NHS has an emphasis on delivery of evidence based practice. It was
      concluded that an active focus on values based practice merits equal attention
      and status.

PMID- 25579666
TI  - Genome sequence determination and metagenomic characterization of a
      Dehalococcoides mixed culture grown on cis-1,2-dichloroethene.
AB  - A Dehalococcoides-containing bacterial consortium that performed dechlorination
      of 0.20 mM cis-1,2-dichloroethene to ethene in 14 days was obtained from the
      sediment mud of the lotus field. To obtain detailed information of the
      consortium, the metagenome was analyzed using the short-read next-generation
      sequencer SOLiD 3. Matching the obtained sequence tags with the reference genome
      sequences indicated that the Dehalococcoides sp. in the consortium was highly
      homologous to Dehalococcoides mccartyi CBDB1 and BAV1. Sequence comparison with
      the reference sequence constructed from 16S rRNA gene sequences in a public
      database showed the presence of Sedimentibacter, Sulfurospirillum, Clostridium,
      Desulfovibrio, Parabacteroides, Alistipes, Eubacterium, Peptostreptococcus and
      Proteocatella in addition to Dehalococcoides sp. After further enrichment, the
      members of the consortium were narrowed down to almost three species. Finally,
      the full-length circular genome sequence of the Dehalococcoides sp. in the
      consortium, D. mccartyi IBARAKI, was determined by analyzing the metagenome with
      the single-molecule DNA sequencer PacBio RS. The accuracy of the sequence was
      confirmed by matching it to the tag sequences obtained by SOLiD 3. The genome is
      1,451,062 nt and the number of CDS is 1566, which includes 3 rRNA genes and 47
      tRNA genes. There exist twenty-eight RDase genes that are accompanied by the
      genes for anchor proteins. The genome exhibits significant sequence identity with
      other Dehalococcoides spp. throughout the genome, but there exists significant
      difference in the distribution RDase genes. The combination of a short-read next
      generation DNA sequencer and a long-read single-molecule DNA sequencer gives
      detailed information of a bacterial consortium.

PMID- 25579668
TI  - Stability of return to work after a coordinated and tailored intervention for
      sickness absence compensation beneficiaries with mental health problems: results
      of a two-year follow-up study.
AB  - PURPOSE: Mental health problems (MHPs) are increasingly common as reasons for
      long-term sickness absence. However, the knowledge of how to promote a stable
      return to work (RTW) after sickness absence due to MHPs is limited. The purpose
      of this study was to assess the effects of a multidisciplinary, coordinated and
      tailored RTW-intervention in terms of stability of RTW, cumulative sickness
      absence and labour market status after 2 years among sickness absence
      compensation beneficiaries with MHPs. METHODS: In a quasi-randomised, controlled
      trial, we followed recipients of the intervention (n = 88) and of conventional
      case management (n = 80) for 2 years to compare their risk of recurrent sickness
      absence and unemployment after RTW, their cumulative sickness absence and their
      labour market status after 2 years. RESULTS: We found no statistically
      significant intervention effect in terms of the risk of recurrent sickness
      absence or unemployment. Intervention recipients had more cumulated sickness
      absence in year one (mean difference = 58 days; p < 0.01) and year two (mean
      difference = 36 days; p = 0.03), and fewer were self-supported at the end of
      follow-up (52% versus 69%; p = 0.02). CONCLUSION: The intervention showed no
      benefits in terms of improved stability of RTW, reduced sickness absence or
      improved labour market status after 2 years when compared to conventional case
      management. IMPLICATIONS FOR REHABILITATION: Evidence for effective return-to
      work (RTW) interventions for people with mental health problems is limited, as
      most research to date has been done in the context of musculoskeletal disorders.
      A complex, multidisciplinary intervention, detached from the workplace, does not
      appear to improve the stability of RTW and may actually lead to more sickness
      absence days and less self-support when compared to conventional case management
      of sickness absence beneficiaries in Denmark. A stronger focus on cooperation
      with social insurance officers and employers may produce better results.

PMID- 25579669
TI  - A systematic review of the effectiveness of stroke self-management programs for
      improving function and participation outcomes: self-management programs for
      stroke survivors.
AB  - PURPOSE: A systematic review of stroke self-management programs was conducted to:
      (i) identify how many and what self-management support strategies were included
      in stroke self-management interventions and (ii) describe whether self-management
      programs effectively improved outcomes, focusing specifically on function and
      participation outcomes. METHODS: Twelve databases were searched for the years
      1986-2012 to identify self-management programs for stroke survivors. Pre-post,
      quasi-experimental and randomized controlled trial study designs were included.
      Descriptive information about the intervention was scrutinized to identify what
      self-management support strategies were present in the intervention and
      comparisons were made between programs using a group versus a one-to-one format.
      All outcomes were included and categorized. RESULTS: The most prominent
      strategies identified in our review were goal setting and follow-up, and an
      individualized approach using structured information and professional support.
      There are indications that self-management programs can significantly increase
      participation and functional ability. However, the high level of clinical
      heterogeneity in program delivery, outcomes and level of stroke severity made it
      impossible to conduct a meta-analysis. Further examination of individual self
      management support strategies, such as linking rehabilitation goal setting to
      post-acute self-management programs, the inclusion of family members and the
      contribution of peer-support is warranted. IMPLICATIONS FOR REHABILITATION: Self
      management programs for stroke survivors. Linking post-acute self-management
      programs to rehabilitation goal setting could improve outcomes. Involving family
      members in self-management programs may benefit stroke survivors.

PMID- 25579670
TI  - Is the smartphone app accurate enough?

PMID- 25579681
TI  - Melanotic neuroectodermal tumor of infancy: review of literature, report of a
      case and follow up at 7 years.

PMID- 25579682
TI  - FMR1 CGG allele length in Israeli BRCA1/BRCA2 mutation carriers and the general
      population display distinct distribution patterns.
AB  - Premature ovarian failure and diminished ovarian reserve have been noted both in
      female BRCA1/BRCA2 mutation carriers and in carriers of the Fragile X syndrome
      FMR1 gene CGG repeat size premutation. Based on the observation that BRCA
      mutation carriers do not harbour long CGG repeats in the FMR1 gene, it was
      hypothesized that BRCA-associated premature ovarian failure is mediated via FMR1.
      To test this notion, we evaluated the distribution of constitutional FMR1
      genotypes in 188 BRCA1/BRCA2 mutation-positive Jewish Ashkenazi women and 15 708
      female, mostly Ashkenazi controls in Israel. BRCA1/BRCA2 mutation carriers
      displayed a unique distribution of FMR1 genotypes compared with controls (p =
      0.018) with a prominence of the shorter CGG alleles (<26 repeats). There was no
      allele size distribution differences within BRCA carriers when comparing cancer
      free (n = 95) and breast cancer affected women (n = 93) (p = 0.43). In
      conclusion, BRCA mutation carriers exhibit a distinct CGG FMR1 repeat size
      pattern compared with the general population, but it is unlikely to account for
      the reported diminished ovarian reserve or act as a modifier breast cancer gene
      in BRCA mutation carriers.

PMID- 25579685
TI  - Utopia or dystopia in an age of confusion.

PMID- 25579686
TI  - On monkeys, machines, and mothers.

PMID- 25579683
TI  - A qrr noncoding RNA deploys four different regulatory mechanisms to optimize
      quorum-sensing dynamics.
AB  - Quorum sensing is a cell-cell communication process that bacteria use to
      transition between individual and social lifestyles. In vibrios, homologous small
      RNAs called the Qrr sRNAs function at the center of quorum-sensing pathways. The
      Qrr sRNAs regulate multiple mRNA targets including those encoding the quorum
      sensing regulatory components luxR, luxO, luxM, and aphA. We show that a
      representative Qrr, Qrr3, uses four distinct mechanisms to control its particular
      targets: the Qrr3 sRNA represses luxR through catalytic degradation, represses
      luxM through coupled degradation, represses luxO through sequestration, and
      activates aphA by revealing the ribosome binding site while the sRNA itself is
      degraded. Qrr3 forms different base-pairing interactions with each mRNA target,
      and the particular pairing strategy determines which regulatory mechanism occurs.
      Combined mathematical modeling and experiments show that the specific Qrr
      regulatory mechanism employed governs the potency, dynamics, and competition of
      target mRNA regulation, which in turn, defines the overall quorum-sensing
      response. 

PMID- 25579687
TI  - Variation of X-chromosomal microsatellites in Belarus within the context of their
      genetic diversity in Europe.
AB  - More and more X-STR data are becoming available for worldwide human populations
      for forensic and anthropological investigations, but the European datasets
      analysed so far represent mainly the central, northern, western and southern part
      of the continent with populations of Eastern Europe being practically
      uninvestigated. In the present study, we assessed genetic variation and linkage
      disequilibrium of 19 X-chromosomal STR markers (DXS7132, DXS7133, DXS7423,
      DXS7424, DXS8377, DXS8378, DXS9895, DXS10074, DXS10075, DXS10079, DXS10101,
      DXS10103, DXS10134, DXS10135, DXS10146, DXS10147, DXS10148, GATA172D05, HPRTB) in
      four regional populations of an Eastern European state of Belarus, including 12
      loci incorporated in the Argus X-12 kit. Our results revealed cumulative power of
      discrimination of the tested X-STR loci to amount to 0.999999999999996 and
      0.999999997 in females and males, respectively. Analysis of molecular variance
      demonstrated regional stratification within the country, excluding the use of a
      common X-STR database for Belarus in forensic casework. However, development of a
      separate X-STR database for the northwestern part of the country or exclusion of
      four loci displaying regional differences from the dataset were shown to
      eliminate the observed geographic substructure among Belarusians. Comparison of
      the Belarusian genotypes with X-STR data from other European populations
      disclosed a geography-driven northeast-southwest gradient extending from Belarus
      and Finland to Iberia and Italy. This study is the first extensive report on
      variation of X-STR markers in populations from Eastern Europe and the first
      comprehensive analysis of diversity of X-chromosomal microsatellites in Europe.

PMID- 25579688
TI  - IPPNW Congress in Astana charts course to nuclear-weapons-free world.

PMID- 25579684
TI  - Myocardin-related transcription factor A regulates conversion of progenitors to
      beige adipocytes.
AB  - Adipose tissue is an essential regulator of metabolic homeostasis. In contrast
      with white adipose tissue, which stores excess energy in the form of
      triglycerides, brown adipose tissue is thermogenic, dissipating energy as heat
      via the unique expression of the mitochondrial uncoupling protein UCP1. A subset
      of UCP1+ adipocytes develops within white adipose tissue in response to
      physiological stimuli; however, the developmental origin of these "brite" or
      "beige" adipocytes is unclear. Here, we report the identification of a BMP7-ROCK
      signaling axis regulating beige adipocyte formation via control of the G-actin
      regulated transcriptional coactivator myocardin-related transcription factor A,
      MRTFA. White adipose tissue from MRTFA(-/-) mice contains more multilocular
      adipocytes and expresses enhanced levels of brown-selective proteins, including
      UCP1. MRTFA(-/-) mice also show improved metabolic profiles and protection from
      diet-induced obesity and insulin resistance. Our study hence unravels a central
      pathway driving the development of physiologically functional beige adipocytes. 

PMID- 25579689
TI  - Pelvic osteomyelitis presenting as groin and medial thigh pain: a resident's case
      problem.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: Groin pain represents a
      diagnostic challenge and requires a diagnostic process that rules out life
      threatening illness or disease processes. Osteomyelitis is a potential fatal
      disease process that requires accurate diagnosis and medical management.
      Osteomyelitis presents a problem for the outpatient physical therapist, as the
      described physical findings for the diagnosis of osteomyelitis are nonspecific.
      DIAGNOSIS: A 67-year-old man with groin and bilateral medial thigh pain was
      referred for physical therapy care to address right adductor weakness and
      generalized deconditioning. He had undergone extensive treatment for bladder
      cancer, with a recent radical cystoprostatectomy and cutaneous urinary diversion
      with an Indiana pouch. Postsurgical magnetic resonance imaging indicated normal
      findings, and the patient was currently being managed by an orthopaedic surgeon,
      who diagnosed the patient as having obturator nerve palsy. The physical
      therapist's examination produced findings inconsistent with this diagnosis.
      Subsequently, nuclear medicine studies revealed pubic symphysitis/osteomyelitis
      with secondary myositis, predominantly affecting the right adductor muscles.
      DISCUSSION: Osteomyelitis represents a difficult problem for the outpatient
      physical therapist. Careful consideration of red-flag symptoms and inconclusive
      physical testing indicate the need for further medical work-up. In this case,
      appropriate medical management led to improvement in patient function,
      highlighting the need for early diagnosis. LEVEL OF EVIDENCE: Differential
      diagnosis, level 4.

PMID- 25579690
TI  - The impact of physical therapy residency or fellowship education on clinical
      outcomes for patients with musculoskeletal conditions.
AB  - STUDY DESIGN: A retrospective cohort design was conducted using data from an
      electronic survey and an existing commercial outcomes database. OBJECTIVE: To
      compare the clinical outcomes of patients with musculoskeletal conditions treated
      by physical therapists who had completed residency or fellowship programs versus
      those who had not. BACKGROUND: There is an increasing focus on specialization
      through postprofessional education in physical therapy residency and fellowship
      programs. Scant evidence exists that evaluates the influence of postprofessional
      clinical education on actual patient outcomes. METHODS: Physical therapists using
      a national outcomes database were surveyed to determine their level of
      postprofessional education. Survey responders were categorized into 1 of 3 groups
      that included no residency or fellowship training, residency trained, or
      fellowship trained. Outcomes for 25 843 patients with musculoskeletal conditions
      treated by 363 therapists from June 2012 to June 2013 were extracted from the
      database. These data were analyzed to identify any differences in functional
      status change and efficiency achieved between the 3 groups. Potentially
      confounding variables were controlled for statistically. RESULTS: The fellowship
      trained group of physical therapists achieved functional status changes and
      efficiency that were greater than those of the other groups. No difference in
      functional status change was observed between the residency group and the
      therapists without residency or fellowship training. The group without residency
      or fellowship training was more efficient than the residency-trained group.
      Fellowship-trained therapists were more likely to achieve greater treatment
      effect sizes than therapists without residency or fellowship training. Residency
      trained therapists were less likely to achieve greater treatment effect sizes
      than the therapists without residency or fellowship training. CONCLUSION: These
      data demonstrate that fellowship training may contribute to statistically greater
      patient outcomes. Residency training did not appear to contribute to improved
      patient functional status change or efficiency. It is unknown whether the
      statistical differences observed would be clinically meaningful for patients.

PMID- 25579691
TI  - Scapular muscle performance in individuals with lateral epicondylalgia.
AB  - STUDY DESIGN: Descriptive, laboratory-based, cross-sectional study. OBJECTIVES:
      To describe scapular musculature strength, endurance, and change in thickness in
      individuals with unilateral lateral epicondylalgia (LE) compared to the
      uninvolved limb and the corresponding limb of a matched comparison group.
      BACKGROUND: Reported poor long-term outcomes for the nonsurgical management of
      individuals with LE suggest a less-than-optimal rehabilitation process. Knowledge
      of scapular muscle function in a working population of individuals with LE may
      help to further refine conservative management of this condition. METHODS: Twenty
      eight patients with symptomatic LE and 28 controls matched by age and sex were
      recruited to participate in the study. Strength of the middle trapezius (MT),
      lower trapezius (LT), and serratus anterior (SA) was measured with a handheld
      dynamometer. A scapular isometric muscle endurance task was performed in prone.
      Changes in muscle thickness of the SA and LT were measured with ultrasound
      imaging. Analysis-of-variance models were used to determine within- and between
      group differences. RESULTS: The involved side of the group with LE had
      significantly lower values for MT strength (P = .031), SA strength (P<.001), LT
      strength (P = .006), endurance (P = .003), and change in SA thickness (P = .028)
      when compared to the corresponding limb of the control group. The involved side
      of the group with LE had significantly lower strength of the LT (P = .023) and SA
      (P = .016) when compared to the uninvolved limb; however, these differences were
      small and of potentially limited clinical significance. CONCLUSION: When compared
      to a matched comparison group, there were impairments of scapular musculature
      strength and endurance in patients with LE, suggesting that the scapular
      musculature should be assessed and potentially treated in this population. Cause
      and effect cannot be established, as the weakness of the scapular musculature
      could be a result of LE.

PMID- 25579692
TI  - Neuroplasticity following anterior cruciate ligament injury: a framework for
      visual-motor training approaches in rehabilitation.
AB  - SYNOPSIS: The neuroplastic effects of anterior cruciate ligament injury have
      recently become more evident, demonstrating underlying nervous system changes in
      addition to the expected mechanical alterations associated with injury.
      Interventions to mitigate these detrimental neuroplastic effects, along with the
      established biomechanical changes, need to be considered in the rehabilitation
      process and return-to-play progressions. This commentary establishes a link
      between dynamic movement mechanics, neurocognition, and visual processing
      regarding anterior cruciate ligament injury adaptations and injury risk. The
      proposed framework incorporates evidence from the disciplines of neuroscience,
      biomechanics, motor control, and psychology to support integrating neurocognitive
      and visual-motor approaches with traditional neuromuscular interventions during
      anterior cruciate ligament injury rehabilitation. Physical therapists, athletic
      trainers, strength coaches, and other health care and performance professionals
      can capitalize on this integration of sciences to utilize visual-training
      technologies and techniques to improve on already-established neuromuscular
      training methods. LEVEL OF EVIDENCE: Therapy, level 5.

PMID- 25579693
TI  - Exercises including weight vests and a patient education program for women with
      osteopenia: a feasibility study of the OsteoACTIVE rehabilitation program.
AB  - STUDY DESIGN: Prospective case series with 1-year follow-up. OBJECTIVES: The
      primary aim was to describe the OsteoACTIVE rehabilitation program and evaluate
      its feasibility in terms of progression, adherence, and adverse events in
      patients with low bone mineral density (BMD) and a healed forearm fracture. The
      secondary aim was to assess changes in measures of function and quality of life.
      BACKGROUND: Previous studies have shown benefits of weight-bearing activities,
      resistance exercises, and balance and coordination training for women with low
      BMD and older adults. However, no studies, to our knowledge, have described or
      examined a rehabilitation program combining the use of weight vests and patient
      education in patients with low BMD. METHODS: Forty-two postmenopausal women with
      osteopenia and a healed forearm fracture attended the OsteoACTIVE program for 6
      months (3 sessions of 60 minutes per week). Feasibility was assessed by
      documenting training progression (load and exercises), program adherence (aiming
      for greater than 80%), and adverse events (joint pain, muscle soreness, and
      falls). Secondary measures included quadriceps strength, BMD, dynamic balance,
      walking ability, and self-report functional outcome measures. All outcome
      measures were recorded preintervention (baseline), postintervention, and at 1
      year follow-up. RESULTS: Thirty-five women (83%) completed the 6-month program
      and 31 women (74%) attended all the follow-up measurement sessions. All
      participants progressed during the rehabilitation program for both load and type
      of exercises. Furthermore, 87% of the participants met the a priori goal of 80%
      adherence, and no participants reported adverse events. Improvements in
      quadriceps strength and BMD of the femoral trochanter were noted at the end of
      the 6-month training period (P<.05). At 1-year follow-up, there were significant
      improvements in quadriceps strength and dynamic balance compared to baseline
      (P<.05). CONCLUSION: The OsteoACTIVE rehabilitation program was feasible and
      achieved progression of training level, had high adherence, and had no adverse
      events. Positive improvements were established in lower extremity function and
      femoral trochanter BMD. Clinical trial registered at ClinicalTrials.gov
      (NCT01357278). LEVEL OF EVIDENCE: Therapy, level 4.

PMID- 25579694
TI  - Suprascapular neuropathy after distal clavicle resection and coracoclavicular
      ligament reconstruction: a resident's case problem.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: Acromioclavicular joint
      pathology is reported to be present in up to 30% of all patients complaining of
      shoulder dysfunction. The operative approach to treating acromioclavicular joint
      disease often includes a distal clavicle excision and, in circumstances of
      acromioclavicular joint instability, reconstruction of the coracoclavicular
      and/or the acromioclavicular ligament. Surgical complications for these
      procedures are rare, but potentially include suprascapular neuropathy secondary
      to the course of the suprascapular nerve posterior to the clavicle prior to
      entering the supraspinatus fossa. DIAGNOSIS: A 28-year-old Caucasian woman
      reported directly to an outpatient physical therapy clinic with a complaint of
      right shoulder weakness. Three years prior, the patient underwent a distal
      clavicle excision and coracoclavicular ligament reconstruction. A detailed
      examination, including diagnostic imaging, identified infraspinatus atrophy and
      weakness, increasing the suspicion for suprascapular nerve injury.
      Electromyography was ordered to confirm the clinical and imaging diagnosis of
      suprascapular neuropathy and to rule out other nerve lesions, especially
      considering the selective atrophy of the infraspinatus muscle without mechanical
      explanation. DISCUSSION: The clinical decision making and systematic use of
      diagnostic testing resulted in identifying a rare case of suprascapular
      neuropathy, selective to the infraspinatus, in a patient who previously underwent
      a distal clavicle excision and coracoclavicular ligament reconstruction. Without
      a spinoglenoid cyst or other suprascapular nerve lesion identified on advanced
      imaging, it is likely that the suprascapular neuropathy identified in this case
      was related to the surgical procedure. LEVEL OF EVIDENCE: Differential diagnosis,
      level 4.

PMID- 25579701
TI  - A follow-up study of neurobehavioral functions in welders exposed to manganese.
AB  - Welders may be exposed to high amounts of manganese (Mn). In this study 63
      welders and 65 referents were followed up with neurobehavioral tests
      approximately 6 years after the initial examination at baseline. The welders were
      exposed to the geometric mean (GM) Mn concentration of 116MUg/m(3) at baseline
      and 148MUg/m(3) at follow-up. Their mean duration of employments as welders was
      19.5 years at follow-up. Being exposed as a welder was associated with a decline
      between baseline and follow-up in the performance on the Static Steadiness Test,
      Finger Tapping Test and Grooved Pegboard Test. However, the decline was also
      associated with having high concentrations of carbohydrate deficient transferrin
      in serum (sCDT), indicating high alcohol consumption. When subjects with sCDT
      above the upper reference limit of the laboratory (>=1.7%) were excluded from the
      analyses, no difference in the decline in performance was observed between
      welders and referents for any of the applied neurobehavioral tests. Three welders
      had developed bradykinesia at follow-up, as assessed by a substantial decline in
      their Finger Tapping Test performance. They had also experienced a severe decline
      in Foot Tapping, Grooved Pegboard and Postural Sway Test scores (while
      blindfolded), while postural tremor as assessed with the CATSYS Tremor 7.0 was
      normal. Their neurobehavioral test performance at baseline 6 years previously had
      been normal. 

PMID- 25579702
TI  - Darbepoetin alfa for anemia with myelodysplastic syndrome.
AB  - The myelodysplastic syndromes are characterized by refractory cytopenias that
      lead to symptomatic anemia, bleeding, and increased risk for infections. For
      almost two decades, the use of darbepoetin and other erythropoietin stimulating
      agents to treat symptomatic anemia in lower-risk myelodysplastic syndromes has
      been a standard of care. This practice is supported by numerous Phase I/II
      studies and one Phase III study demonstrating the benefit of using erythropoietin
      stimulating agents alone, or in combination with granulocyte colony stimulating
      factor, for treatment of symptomatic anemia with the goal of decreasing red blood
      cell transfusion requirements. This review summarizes the published experience
      regarding the use of erythropoietin stimulating agents, with a special focus on
      darbepoetin, in patients with myelodysplastic syndrome and symptomatic anemia. 

PMID- 25579703
TI  - Rediscovering drug discovery.

PMID- 25579704
TI  - Recent advances towards the fabrication and biomedical applications of responsive
      polymeric assemblies and nanoparticle hybrid superstructures.
AB  - Responsive polymeric assemblies and hybrid superstructures fabricated from
      stimuli-sensitive polymers and inorganic nanoparticles (NPs) have been the
      subject of extensive investigations during the past few decades due to their
      distinct advantages such as an improved water solubility, stimuli-responsiveness,
      excellent biocompatibility, and facile introduction of functional units. In
      addition, the chemical compositions of polymeric assemblies and corresponding
      hybrid superstructures can be modulated via the initial synthetic design to
      target desired functions, fabricate smart nanostructures, and explore morphology
      dependent functional optimization. Promising applications in the field of
      imaging, sensing, drug/gene delivery, diagnostics, and nanoreactors are being
      extensively investigated. This perspective article focuses on recent
      developments, microstructural control, and biomedical applications of stimuli
      responsive polymeric assemblies as well as responsive hybrid superstructures
      fabricated from responsive polymers and inorganic NP building blocks (gold NPs
      and magnetic iron oxide NPs), and highlights their current status and future
      developments with selected literature reports. 

PMID- 25579707
TI  - Crystalline structures of polymeric hydrocarbon with 3,4-fold helical chains.
AB  - Molecular hydrocarbons are well-known to polymerize under pressure to form
      covalently bonded frameworks. Here we predict by ab initio calculations two
      distinct three-dimensional hydrocarbon crystalline structures composed of 3-fold
      and 4-fold helical CH chains in rhombohedral (R3) and tetragonal (I41/a)
      symmetry, respectively. Both structures with 1:1 stoichiometry are found to be
      energetically more favorable than solid acetylene and cubane, and even more
      stable than benzene II solid at high pressure. The calculations on vibrational,
      electronic, and optical properties reveal that the new chiral hydrocarbons are
      dynamically stable with large bulk moduli around 200 GPa, and exhibit a
      transparent insulating behavior with indirect band gaps of 5.9 ~ 6.7 eV and
      anisotropic adsorption spectra. Such forms of hydrocarbon, once synthesized,
      would have wide applications in mechanical, optoelectronic, and biological
      materials.

PMID- 25579708
TI  - Post-transplant venous thromboembolic events and their effect on graft survival.
AB  - Venous thromboembolic events (VTEs) are a major cause of post-operative morbidity
      and mortality. Our objective is to establish the prevalence of VTEs in kidney
      transplant recipients and assess its impact on graft survival. Data regarding
      renal transplant patients with VTEs from 1985 to 2010 were identified and
      analyzed. After excluding recipients of combined grafts and late VTE development,
      1596 recipients were included in this analysis. The prevalence of post-operative
      VTEs and graft survival were determined. Cox regression was used to analyze the
      survival data and data on prognostic (confounding) variables. The observed
      prevalence of VTEs in kidney transplant recipients was 1.6%. Of the 1596 kidney
      recipients, 25 recipients who developed VTEs had a mean graft survival of 12.3
      years (compared with 20.5 years in patients without). The hazard ratio was 1.1
      (95% confidence interval: 0.4-3.0, P = 0.447). The prevalence of VTEs post kidney
      transplantation is small. Although it did not reach statistical significance, it
      increased the risk of graft failure by 30%. 

PMID- 25579709
TI  - Mycobacterial infection and the impact of rifabutin treatment in organ transplant
      recipients: a single-center study.
AB  - Tuberculosis (TB) is a frequently encountered infection among organ transplant
      recipients in developing countries, and the incidence of infection after the
      first year of transplantation is considerably high. In this study, the impact of
      rifabutin treatment on organ transplant recipients with TB infection was
      evaluated with respect to the trend of infection, management and outcome. The
      medical records of 26 post-transplant patients who received an organ transplant
      between 2004 and 2012 and later diagnosed with TB of different organs were
      reviewed retrospectively. We retrieved data regarding clinical features as well
      as treatment and outcomes. The median time interval between transplantation and
      TB was 36 months (IQR 12-101 months). The most common form of infection was
      pulmonary/pleural TB. All our subjects received rifabutin instead of rifampin in
      the anti-TB treatment regime as rifabutin is a less-potent inducer of cytochrome
      P-450. All patients responded satisfactorily to the treatment and maintained
      excellent allograft function. Moreover, we did not have any mortality among our
      recipients. Drug-induced hepatitis was observed in nine (35%) patients. Rifabutin
      is an excellent alternative medication to rifampin in the setting of TB
      management. Hepatotoxicity is a potential risk for treatment because of the
      potential additive toxicity of immunosuppressive drugs. 

PMID- 25579710
TI  - Stress and burnout among hemodialysis nurses: a single-center, prospective survey
      study.
AB  - Stress is a well known and identified problem within the nursing profession.
      Dialysis nurses are exposed to high level of stress. Increasing workload can
      aggravate stress and cause burnout and exhaustion. Stress and burnout are capable
      of having a detrimental impact on organizational productivity and pose serious
      health and safety hazards on the job. We aimed in this study to determine the
      type and level of stress and the amount of burnout among our dialysis nurses, and
      to evaluate the managing skills and the impact of stress on their work
      performance. There were 93 nurses (19 national and 74 expatriate nurses) who
      answered modified questionnaires to the aims of our prospective and descriptive
      correlational study. Our results show that most nurses involved in the study
      (national and expatriate) experienced a mild level of stress (79% and 68%,
      respectively) and moderate level of burnout (42% and 38%, respectively). The most
      common stressor among the national nurses was technical breakdowns of machines
      (15.9%) and that among expatriates was job insecurity (16.9%). The majority of
      the national nurses (21%) coped with this by increased sick leaves, whereas the
      majority (25%) of the expatriates responded by becoming easily frustrated. The
      most utilized coping skill among both groups was the relaxation methods (20.8%
      versus 24.9%) and the least utilized was denial (3.9% versus 0.5%). In
      conclusion, our results suggest the exposure of dialysis nurses to different
      types of stress and demonstrate the different experienced coping skills. These
      results may have implications for nursing management and hospital administration.

PMID- 25579711
TI  - Serum hepcidin levels in patients with end-stage renal disease on hemodialysis.
AB  - Patients on hemodialysis (HD) are usually anemic because of defective
      erythropoeisis. Hepcidin is a polypeptide that regulates iron homeostasis and
      could serve as an indicator of functional iron deficiency in patients with end
      stage renal disease (ESRD); this may also aid in the assessment of patient's
      response to erythropoietin (EPO). The present study was directed to investigate
      serum levels of hepcidin, iron status and inflammation markers such as C-reactive
      protein (CRP) in patients with ESRD on maintenance HD and to observe the
      correlation of serum hepcidin with conventional iron and inflammatory markers. A
      total of 42 patients of both sexes on maintenance HD and EPO therapy were
      enrolled; 42 ageand sex-matched healthy subjects were included as controls.
      Laboratory tests including complete blood count, serum hepcidin, total iron
      binding capacity (TIBC), serum ferritin, serum iron and CRP were performed. Serum
      hepcidin levels were significantly higher in patients with ESRD than in the
      control group (18.2 +/- 2.8 ng/mL and 8.5 +/- 2.3 ng/mL, respectively P = 0.000).
      The hemoglobin, hematocrit, serum iron, TIBC and transferrin saturation levels in
      the patient group were significantly lower than in the control group. Higher
      hepcidin levels were found in EPO non-responders (19.6 +/- 2.4 ng/mL) while lower
      levels (16.9 +/- 2.5 ng/mL) were seen in responders (P = 0.001). A positive and
      significant correlation was observed between the values of serum hepcidin and
      CRP. Our study indicates that higher hepcidin levels are found in ESRD patients
      on HD and in those not responding to EPO. Our findings suggest that hepcidin
      might play a role in the pathophysiology of anemia associated with chronic
      diseases as well as EPO resistance. 

PMID- 25579712
TI  - Relationship between asymmetric dimethylarginine plasma level and left
      ventricular mass in hemodialysis patients.
AB  - Left ventricular hypertrophy (LVH) and left ventricular dysfunction are highly
      prevalent in patients with end-stage renal disease (ESRD). Several studies
      suggest that left ventricular mass and function is strongly modulated by the
      nitric oxide (NO) system. Asymmetric dimethylarginine (ADMA), an endogenous
      inhibitor of endothelial-based NO synthase, is emerging as an important
      cardiovascular risk factor in ESRD patients. Our objective is to evaluate the
      relationship between plasma ADMA level and LVH among hemodialysis (HD) patients.
      Plasma ADMA measurements by enzyme-linked immunesorbent assay and
      echocardiographic evaluation were performed for 40 patients on regular HD, 20
      patients with pre-dialysis chronic kidney disease, 20 hypertensive patients with
      left ventricular hypertrophy and normal kidney function and 20 healthy age and
      sex-matched subjects as a control group. Residual renal function (RRF) was
      measured in HD patients by urea clearance from a urine collection. Mean values of
      plasma ADMA level were significantly high in all patient groups when compared
      with the control group (P < 0.001). However, there was no significant difference
      between groups I, II and III as regards mean values of plasma ADMA (P >0.05) and
      between ADMA and RRF in HD patients (r = -0.20, P = 0.60). It was also seen that
      plasma ADMA was not correlated with left ventricular mass index; however, there
      could be an association between ADMA level and diastolic dysfunction. The plasma
      ADMA level was found to be high in the three studied patient groups in comparison
      with the control group. HD is not an effective procedure for adequate removal of
      ADMA. 

PMID- 25579713
TI  - Comparison of serum levels of hepcidin and pro-hepcidin in hemodialysis patients
      and healthy subjects.
AB  - Hepcidin prevents absorption of iron from the intestine and inhibits release of
      iron from macrophages and hepatocytes. For this reason, it seems that high levels
      of hepcidin are a predisposing factor for anemia in chronic inflammatory
      conditions such as chronic kidney disease and dialysis patients. This study was
      designed to determine the role of changes in the level of serum hepcidin in the
      management of hemodialysis patients. This study included 44 dialysis patients and
      44 controls. The hepcidin and pro-hepcidin levels were measured by the enzyme
      linked immunosorbent assay method. The serum ferritin level was measured by the
      chemiluminescence method. The mean hepcidin level was 999.3 +/- 996.7 ng/mL in
      the case group and 770.4 +/- 815.9 ng/mL in the control group (P = 0.25). The
      mean pro-hepcidin level was, respectively, 186.1 +/- 220.3 pg/mL and 150.87 +/-
      207.7 pg/mL, in the case group and control groups (P = 0.45). The mean (standard
      deviation) ferritin level was 816.4 +/- 379.4 ng/mL in the case group and 193 +/-
      171.8 ng/mL in the control group (P < 0.001). In the case group, the correlation
      between serum ferritin and hepcidin was not significant (r = 0.6, P = 0.08).
      Also, there was no significant correlation between serum ferritin and pro
      hepcidin levels (r = 0.6, P = 0.08). A positive correlation was seen between pro
      hepcidin and hepcidin levels (r = 0.92, P < 0.01). In this study, the results
      showed that the serum hepcidin levels are high in dialysis patients and that
      there was no correlation with the serum ferritin levels.

PMID- 25579714
TI  - The effect of on-line hemodiafiltration on improving the cardiovascular function
      parameters in children on regular dialysis.
AB  - The cardiovascular disease is an important cause of morbidity and accounts for
      almost 50% of deaths in patients undergoing maintenance dialysis. Many harmful
      molecules of the uremic milieu, such as the middle molecules, are difficult to
      remove by conventional hemodialysis (HD). On-line hemodiafiltration (OL-HDF) can
      achieve a considerable clearance of middle molecules and, together with its
      sterile ultrapure infusate, may have favorable effects on inflammation and
      cardiovascular complications. We aimed in this study to assess the effect of OL
      HDF on improving the chronic inflammatory state associated with chronic kidney
      disease and the possible impact of these changes on myocardial function in
      chronic HD children. Thirty pediatric patients [12 (40%) males and 18 (60%)
      females with a mean age of 11.3 +/- 3.2 years] on conventional HD for at least
      six months were switched to OL-HDF for six months. Variables for comparison at
      the end of each period included the levels of serum C-reactive protein and Kt/V
      as well as electrocardiography and echocardiographic measurements, including left
      ventricular mass index (LVMI). On changing from HD to OL-HDF, there was a
      significant decrease in hs-CRP (from 7.9 +/- 8.9 to 3.4 +/- 3 MU g/mL) (P = 0.01)
      and frequency of diastolic dysfunction (P = 0.04), while systolic function (FS
      and EF) improved significantly (P = 0.007 and 0.05, respectively), while LVMI did
      not change. We conclude that OL-HDF was well tolerated in children with
      improvement of the systolic function of the myocardium and the overall frequency
      of diastolic dysfunction. 

PMID- 25579716
TI  - Acute kidney injury in severe acute pancreatitis: an experience from a tertiary
      care center.
AB  - Acute kidney injury (AKI) is an important cause of morbidity and mortality in
      severe acute pancreatitis (SAP). We aimed in our study to explore the risk
      factors of AKI in patients with SAP and assess the prognosis of patients with SAP
      and AKI. This is a retrospective study consisting of analysis of outcome and
      complications encountered in 72 severe acute pancreatitis patients admitted to a
      tertiary care center at Indore, India, from May 2011 to April 2012. We
      encountered 14 AKI cases in the SAP study patients. There was a significant
      association of diabetes and alcohol with AKI in patients with SAP. Alcohol was
      found to be an independent significant risk factor for AKI in SAP. All the eight
      patients with SAP who expired had AKI. None of the patients of SAP without AKI
      expired during the study. We conclude that the patients with SAP with AKI have a
      greater mortality rate as compared with the SAP patients without AKI. 

PMID- 25579715
TI  - Rituximab as a rescue therapy in patients with glomerulonephritis.
AB  - To evaluate the use of rituximab in the treatment of severe glomerulonephritis
      (GN) in order to prevent progression of kidney disease toward the end stage, we
      designed a multicenter, retrospective study in Saudi Arabia about the efficacy
      and safety of the use of "off label" rituximab in a variety of severe refractory
      GN to conventional treatment and the progression of kidney disease for at least
      one year of follow-up. All the patients had kidney biopsies before treatment with
      rituximab, and proteinuria and glomerular filtration rate (GFR) were followed-up
      for the period of the study. The immediate side-effect at the time of
      administration of rituximab included itching in three patients, hypotension in
      one patient and anaphylaxis in one patient (dropped out from the study). After
      the administration of rituximab in 42 patients and during the first six months of
      therapy, 16 (38%) patients had complete remission (CR), 13 (31%) patients had
      partial remission (PR) and 13 (31%) patients had no remission. The mean follow-up
      period for the patients was 19.0 +/- 6.97 months (median 18.0 months). The long
      term follow-up during the study period disclosed a good hospitalization record
      for almost all of the patients. Membranous GN (MGN) was the largest group in the
      cohort (58% of the patients), and we observed CR and PR in 40% and 28% of them,
      respectively, which was comparable with the previous experience with rituximab in
      MGN patients with more CR than PR in our cohort. We conclude that our study
      suggests the safety and efficacy of the use of rituximab in patients with
      refractory GN and that larger and long-term prospective studies are required to
      define the role of rituximab in the different categories of these diseases. 

PMID- 25579717
TI  - Effects of Salacia oblonga on cardiovascular risk factors in chronic kidney
      disease patients: a prospective study.
AB  - The present study is aimed to evaluate the effect of the herbal drug Salacia
      oblonga on reduction of cardiovascular risk factors in patients with chronic
      kidney disease (CKD). Sixty patients were randomized in four groups; group A1 =
      non-diabetic CKD given trial drug Salacia oblonga for six months, group A 2 = non
      diabetic CKD intended to receive placebo, group B1 = diabetic CKD treated with
      Salacia oblonga for six months and group B 2 = diabetic CKD patients intended to
      receive placebo. Estimation of renal function tests including blood urea, serum
      creatinine and creatinine clearance was performed at baseline and after that at
      monthly intervals. Lipid profile, interleukin-6 (IL-6) and C-reactive protein
      (CRP) were measured at baseline and were repeated at three months and six months.
      After six months of treatment, Salacia oblonga could reduce the triglyceride
      levels by 23.66% (P = 0.008) in non-diabetic and by 17.45% (P = 0.01) in diabetic
      CKD patients. In comparison with placebo, both non-diabetic and diabetic CKD
      patients treated with Salacia oblonga showed significant reduction in CRP levels
      (P = 0.002 and 0.03, respectively), while significant reduction in IL-6 (P-value
      = 0.0003) and serum cholesterol levels (P-value = 0.0001) was seen only in
      diabetic CKD patients treated with Salacia oblonga. Stabilization of creatinine
      clearance with Salacia oblonga was observed in both non-diabetic (P = 0.05) and
      diabetic CKD (P = 0.04) patients in comparison with placebo. Salacia oblonga has
      significant beneficial effects on lipid profile and markers of inflammation and
      endothelial dysfunction in CKD patients. Salacia oblonga also seems to have a
      reno-protective effect, as reflected by stabilization of creatinine clearance at
      six months in this study. 

PMID- 25579719
TI  - Exploring the opinion of hemodialysis patients about their dialysis unit.
AB  - Hemodialysis (HD) patients are subjected to a number of physical and mental
      stresses. Physicians might be unaware of some of these problems. We assessed our
      patients' opinion about the service provided at the dialysis unit. Our unit has
      89 patients on HD. A questionnaire exploring our patients' opinion relative to
      the service provided was prepared. The patients were asked to fill-in the
      questionnaire in a confidential manner. Questionnaires were then collected and
      examined while unaware of patient identities. Sixty-nine patients (77.5%)
      responded to the questionnaire. Eight patients (11.6%) revealed their names on
      the questionnaire. According to the questionnaire, the patients were asked to
      assess the service of each service by choosing one of the following grades:
      "excellent," "mediocre" or "bad." For the whole group of contributing patients,
      there were 563 "excellent," 85 "mediocre" and five "bad" choices in addition to
      37 blank "no comment" choices. Food service had the least percentage (68%) of
      evaluation as "excellent," while doctor' performance got the highest excellent
      evaluation (85.5%). Thirty-five patients (50.7%) added further comment(s). An
      audit meeting was conducted to discuss these results. Exploring the opinion of
      patients on HD might uncover some areas of dissatisfaction and help in improving
      the provided service. We recommend widespread usage of questionnaires to assess
      patient satisfaction as well as to assess other health-care aspects. 

PMID- 25579718
TI  - Incidence of acute kidney injury in the neonatal intensive care unit.
AB  - The aim of this work is to study the incidence of acute kidney injury (AKI) in
      neonates admitted to the neonatal intensive care unit (NICU) over a six-month
      period from September 2011 to March 2012. This prospective study was performed on
      250 neonates admitted to the NICU at the Children's Hospital, Faculty of
      Medicine, Zagazig University. All neonates were subjected to detailed history
      taking, including pre-natal, natal and post-natal history, with stress on
      symptoms suggestive of AKI. All neonates were examined thoroughly and the
      following investigations were performed: Blood urea nitrogen (BUN), serum
      creatinine, sodium, potassium, calcium, complete blood count, C-reactive protein,
      arterial blood gases, urine sodium and urine creatinine. AKI was diagnosed in 27
      cases (10.8%), including 12 females and 15 males. 40.7% of the AKI cases were
      born after full-term pregnancy while 59.3% were pre-term babies. 29.6% of the AKI
      cases had oliguria, and there was male sex predominance, with a male-female ratio
      of 1.3:1. The cause of AKI was pre-renal in 96.3% and intrinsic renal in 3.7% of
      the cases. The predisposing factors for AKI were sepsis in 63% of the cases,
      respiratory distress syndrome in 55.6%, mechanical ventilation in 51.9%, peri
      natal asphyxia in 18.5%, dehydration in 14.8%, surgical operation in 11.1%,
      congenital heart disease in 7.4%, sub-galeal hematoma in 3.7%, polycythemia in
      3.7% and intra-ventricular hemorrhage in 3.7% of the cases. Our data suggest that
      pre-renal failure was the most common form of AKI in our patients. Early
      recognition of risk factors such as sepsis, peri-natal asphyxia or peri-operative
      problems and rapid effective treatment of contributing conditions will reduce the
      incidence of AKI in the neonatal period. 

PMID- 25579720
TI  - Therapeutic efficacy of a biosimilar epoetin alfa in hemodialysis patients.
AB  - Anemia is a frequent complication in patients with chronic kidney disease.
      However, human recombinant erythropoietin (rHu-EPO) has revolutionized the
      management of anemia in chronically dialyzed patients. Epomax (r) is a new rHu
      EPO alfa manufactured in Tunisia (Medis Laboratories). The aim of this study was
      to evaluate the efficacy and tolerance of Epomax (r) in chronic hemodialysis (HD)
      patients in a phase-III, multicenter, clinical trial. Fiftythree HD patients
      (mean age 47.7 +/- 13 years) who received a stable dose of rHu-EPO (Hemax (r) , a
      rHu-EPO alfa manufactured by Biosidus Laboratories) subcutaneously were switched
      to Epomax (r) via the same route of administration. At baseline, the mean
      systolic pressure was 132 +/- 18 mm Hg and the mean diastolic pressure was 79 +/-
      8 mm Hg. The mean blood hemoglobin was 10.2 g/dL and the median ferritin level
      was 667 ng/mL. After a follow-up of 43 days, the mean blood hemoglobin was 10.5
      g/dL under the effect of Epomax (r) . There was no significant difference in the
      mean hemoglobin levels between the treatments with both drugs. Few adverse events
      were reported during the study. We conclude that Epomax (r) was effective at
      maintaining the hemoglobin levels at target concentrations and was well tolerated
      in HD patients. 

PMID- 25579721
TI  - Evaluation of the effect of duration on dialysis on echocardiographic parameters:
      a preliminary study.
AB  - The excessive cardiovascular mortality seen in patients with end-stage renal
      disease seems to be closely related to accelerated coronary atherosclerosis. Some
      echocardiographic parameters such as left ventricular mass and diastolic
      dysfunction are implicated in ventricular dysfunction and mortality. The aim of
      the present study was to evaluate the effect of duration on dialysis on some
      echocardiographic parameters. We enrolled 75 patients on hemodialysis, including
      34 women, in our prospective study. The mean age was 42.5 +/- 13.8 years. The
      echocardiographic parameters were all measured within 2 h after a dialysis
      session. The study population was divided into two groups: Group-1 consisted of
      patients on dialysis for < 5 years and group-2 included patients on dialysis for
      >5 years. The two groups were similar regarding demographic characteristics and
      cardiovascular risk factors. On univariate analysis, a statistically significant
      difference was seen in the left ventricular end-diastolic diameter (P = 0.002),
      left ventricular end-syslotic diameter (P = 0.008), left ventricular mass (P =
      0.006), inter-ventricular septum (P = 0.024), mitral flow deceleration time (P =
      0.03), tricuspid anteroposterior systolic excursion (P = 0.01), inferior vena
      cava diameter (P = 0.04), left atrial size (P = 0.02), valvular calcification (P
      = 0.01) and pericardial effusion (P = 0.01) between the two groups. We conclude
      that the duration on dialysis is associated with changes in several
      echocardiographic parameters. Frequent follow-up with echocardiogram is
      recommended in the management of these patients. 

PMID- 25579722
TI  - Evaluation of thyroid hormone levels in chronic kidney disease patients.
AB  - We attempted in this study to determine the thyroid hormone levels in 45 adult
      chronic kidney disease (CKD) patients and 45 ageand sex-matched healthy subjects
      as controls. The serum thyroid hormone levels were measured by a
      radioimmunoassay. Serum concentrations of creatinine, urea, electrolytes and
      total proteins and albumin were measured as well. There was a significant
      decrease in the levels of serum total T3, total T4 and total protein and albumin
      levels in CKD patients when compared with the controls. There was a significant
      increase in the level of thyroid stimulating hormone in the CKD patients compared
      with the controls. Our study suggests that CKD leads to significant changes in
      the thyroid hormone levels, which need to be interpreted carefully in these
      patients. 

PMID- 25579723
TI  - Polyomavirus-associated nephropathy in renal and simultaneous pancreas-kidney
      transplant recipients: report of three cases.
AB  - Infection with polyomavirus (BK virus) is the cause of renal graft losses in more
      than 50% of the infected cases. There should be a high index of suspicion about
      this disease, although the incidence is only between 2% and 5% as the future of
      renal graft depends on the early and appropriate management of the same. Herein,
      we describe three clinical cases: Two were those of kidney transplant and the
      third, a combined kidney-pancreas transplant. In these cases, by reducing
      immunosuppression and, in one case, replacing the calcineurin inhibitor by MTOR
      (mammalian target of rapamycin) in addition, we were able to preserve of the
      normal function of the transplanted organs. 

PMID- 25579724
TI  - Strongyloides stercoralis infection in kidney transplant recipients.
AB  - Strongyloides stercoralis is an uncommon infection in Saudi Arabia. It can
      establish latency and cause an autoinfection in humans that lasts for years. The
      infection can get reactivated during immunosuppression and can result in a life
      threatening Strongyloides hyperinfection syndrome. We present three cases of
      renal transplant recipients who developed Strongyloides infection following
      transplantation. A bronchoalveolar lavage specimen, a duodenal biopsy and/or a
      stool specimen from these patients revealed evidence of S. stercoralis larvae.
      The first two patients received kidneys from the same deceased donor, a native of
      Bangladesh, an area that is highly endemic for S. stercoralis. The data suggest
      that the first two cases might be donor derived. High-risk donors and recipients
      should be screened for Strongyloides infection to initiate treatment before
      transplantation thus reducing morbidity and mortality. 

PMID- 25579725
TI  - Carcinoma of the tongue in a renal transplant recipient: a rare post-transplant
      malignancy.
AB  - Current immunosuppression improved long-term outcome of transplant patients, but
      it also increased the incidence of de novo malignancy. Organ transplant
      recipients have a three to four-fold increased risk of developing carcinoma in
      comparison with the general population. Common malignancies encountered after
      transplantation include cancer of the skin, lips, post-transplant
      lymphoproliferative disease, ano-genital carcinoma and Kaposi sarcoma. Squamous
      cell carcinoma of the tongue is very rare. We report here a case of squamous cell
      carcinoma of the tongue in an adult male patient who developed it 11 years post
      transplant. He underwent right hemiglossectomy and his graft function remained
      stable.

PMID- 25579726
TI  - Successful recovery from iatrogenic severe hypernatremia and severe metabolic
      acidosis resulting from accidental use of inappropriate bicarbonate concentrate
      for hemodialysis treatment.
AB  - Bicarbonate dialysis is the treatment modality of choice for correction of
      metabolic acidosis in chronic renal failure. However, improper selection of
      dialysate concentrate can result in life-threatening human errors. We report a
      case of iatrogenic severe hypernatremia (sodium 207 mEq/L) and severe metabolic
      acidosis (pH 6.65) that resulted due to accidental use of inappropriate
      bicarbonate concentrate for hemodialysis treatment. There was successful recovery
      in this patient with no neurological sequelae. To the best of our knowledge, this
      is the first case report in adults of severe hypernatremia along with severe
      metabolic acidosis due to error in the preparation of dialysis fluid. 

PMID- 25579727
TI  - Pregnancy in peritoneal dialysis and an infant with a ventricular septal defect.
AB  - Fertility is markedly reduced in dialysis patients. Estimates of the frequency of
      conception in dialysis patients range from 1.4% per year in Saudi Arabia to 0.5%
      in the United States. The reasons for the rarity of pregnancy in dialysis
      patients are not well understood. In addition, there is a marked increase in the
      risk of pre-eclampsia, hydramnios, hypertension crisis, early uterine
      contractions and pre-term delivery. Herein, we report a 38-year-old Saudi woman
      with chronic renal failure who completed the full term of pregnancy uneventfully
      on peritoneal dialysis. Using a biocompatible dialysate solution, adequate
      metabolic and blood pressure control were achieved during pregnancy. The
      delivered infant was small for gestational age and was born with a ventricular
      septal defect. To the best of our knowledge, this is the first case report in the
      literature of ventricular-septal defect in an infant born to a mother on
      peritoneal dialysis. 

PMID- 25579728
TI  - Mesangioproliferative glomerulonephritis in a patient with Kimura's disease
      presenting as Nephrotic syndrome.
AB  - Kimura's disease is a rare chronic eosinophilic inflammatory disorder of unknown
      etiology. Majority of cases have been reported from South East Asia, while
      sporadic occurrences have been reported worldwide, including the Indian
      subcontinent. Nephrotic syndrome may be the presenting manifestation of Kimura's
      disease, and a variety of renal lesions are observed histologically in such
      patients. We herein describe a case of steroid-responsive mesangioproliferative
      glomerulonephritis related to kimura's disease. 

PMID- 25579729
TI  - Distal renal tubular acidosis with nerve deafness secondary to ATP6B1 gene
      mutation.
AB  - Autosomal recessive distal renal tubular acidosis (dRTA) is associated with
      mutation in the ATP6B1 gene encoding the B1 subunit of H + -ATPase, one of the
      key membrane transporters for net acid excretion of alpha-intercalated cells of
      medullary collecting ducts. Sensori-neural deafness frequently accompanies this
      type of dRTA. We herewith describe a patient who had distinct features of dRTA
      with bilateral sensori-neural hearing loss and ATP6B1 mutation. This is a rare
      entity. 

PMID- 25579730
TI  - Lithium overdose: early hemodialysis is the key!
AB  - A 65-year-old gentleman was referred to our hospital with encephalopathy and
      renal failure. His medications included lithium for the treatment of bipolar
      disorder. The clinical examination and the laboratory investigations that
      followed revealed findings classical of lithium overdose. The patient was
      successfully managed and discharged from the hospital on Day 9 of admission.
      Clinicians should be aware of this rather unusual and relatively rare
      differential cause of acute on chronic renal failure with encephalopathy. 

PMID- 25579731
TI  - Metformin-related acidosis in a woman while performing Haj: a conservative
      approach.
AB  - Metformin is a first-line oral anti-hyperglycemic agent. It decreases insulin
      resistance, decreases hepatic glucose output and enhances peripheral glucose
      uptake. Metformin is used as a monotherapy in combination with other oral
      hypoglycemic agents. A major side-effect of metformin is lactic acidosis. The
      elimination of metformin is mainly through the kidneys, and raised plasma
      concentrations can cause lactic acidosis. Provided there is no overdose,
      metformin associated lactic acidosis rarely develops in patients without co
      morbidities such as renal or hepatic insufficiency, acute infection or severe
      dehydration. Herein, we report a case of metformin-induced metabolic acidosis
      occurring in a woman who was severely dehydrated after performing Haj and treated
      conservatively.

PMID- 25579732
TI  - Intraperitoneal streptokinase use-associated eosinophilic peritonitis.
AB  - Eosinophilic peritonitis (EP) is an uncommon complication of peritoneal dialysis,
      which happens usually secondary to either an underlying bacterial, fungal or
      tubercular infection or as a reaction to intraperitoneal drugs or constituents of
      the dialysis system like tubings or solution. We report a case of a middle aged
      male who was initiated on continuous ambulatory peritoneal dialysis. Because of
      inadequate inflow and outflow of dialysis fluid, he was given two doses of
      intraperitoneal streptokinase after ruling out other causes. After the use of
      intraperitoneal streptokinase, there was turbid effluent with culture showing
      Staphylococcus aureus. Even after the successful treatment of bacterial
      peritonitis with intravenous antibiotics, he continued to have turbid effluent,
      with a predominance of eosinophils in the effluent cell count. A diagnosis of EP
      was made and he was managed with the antihistaminic drug loratidine, with
      complete resolution. 

PMID- 25579733
TI  - Amyloidosis in Behcet's disease.
AB  - Behcet's disease (BD) is a multisystem vasculitis with protean manifestations. It
      is characterized by a heightened state of inflammation, although the factors that
      initiate and sustain this inflammation are not clear. We report some cases of BD
      associated amyloidosis and have similar features. The patients developed
      nephrotic syndrome due to secondary amyloidosis, which was refractory to the
      immunosuppressive agents. Two patients expired and the third was lost to follow
      up during the course. The BD complicated with amyloidosis is associated with high
      mortality despite the current aggressive therapy. 

PMID- 25579734
TI  - Arterovenous fistula creation using the brachial artery and cubital fossa veins:
      a viable option in our environment.

PMID- 25579735
TI  - Plasmapheresis in renal diseases: personal experience.

PMID- 25579736
TI  - Epidemiologic and demographic characteristics of a hemodialysis patient in
      Quchan, Iran.

PMID- 25579737
TI  - Diabetic nephropathy in hemodialysis patients in Constantine, Algeria.

PMID- 25579738
TI  - Barriers to adequate urea clearance among hemodialysis patients in developing
      countries: an example from the Sudan.

PMID- 25579739
TI  - Irreversible renal failure in two infants.

PMID- 25579740
TI  - Chinese H7N9 bird flu: a concern on kidney involvement.

PMID- 25579741
TI  - Eligibility for renal transplantation: a Moroccan interregional survey.
AB  - In the treatment of end-stage renal disease, kidney transplantation (KT) is the
      best and most cost-effective alternative with regard to both prognosis and
      quality of life. To identify the proportion and the characteristics of kidney
      transplant candidates who can be considered eligible, a total of 2066
      hemodialysis patients were investigated as part of the ARTEMIS (Attitude toward
      Renal Transplantation and Eligibility among dialysis patients in a Moroccan
      Interregional Survey) study. We investigated all patients receiving hemodialysis
      in the 39 centers of four Moroccan departments. The mean age was 52.9 years and
      the mean duration of hemodialysis was 55.3 months. Fifty-eight percent of our
      patients were considered eligible for KT; 18.2% had an absolute contraindication
      and 23.8% had one or more relative contraindications. When compared with eligible
      patients (n = 1200) in the univariate analysis, those ineligible were
      significantly older (61 years vs. 51, P < 0.0001), had no residual diuresis
      (59.8% vs. 49.1%, P < 0.0001), were more often diabetic (25.1% vs. 11.9%, P <
      0.0001) and hypertensive (54.5% vs. 45.8%, P < 0.0001), and their median dialysis
      duration was longer (61 months vs. 51, P < 0.0001). In the multivariate models,
      eligibility remained associated with young age, less term of dialysis and
      residual diuresis. Adequate control of cardiovascular risk factors before
      dialysis and early referral for transplantation might help to improve eligibility
      of the renal transplant candidates. 

PMID- 25579742
TI  - Proteinuria in Egyptian renal transplant recipients.
AB  - To evaluate the prevalence, risk factors, possible etiology, prognosis and
      management of proteinuria in renal transplant recipients, we studied 435 adult
      renal transplant recipient patients randomly selected from our center; 394
      patients were reviewed retrospectively and 41 patients were followed-up
      prospectively for a period of one year. The patients were classified into three
      groups according to the results of urinalysis and spot urinary albumin creatinine
      ratio: Group A patients with normoalbuminuria; Group B patients with
      microalbuminuria; and Group C patients with macroalbuminuria. Persistent post
      transplantation proteinuria was detected in 125 (28.8%) patients. The etiology of
      post-transplantation proteinuria included chronic allograft dysfunction in 44
      (35.2%) patients, acute rejection in 40 (32%) patients, transplant glomerulopathy
      in eight (6.4%) patients, glomerular disease in 16 (12.8%) patients and other
      etiology in 17 (13.6%) patients. Proteinuric patients demonstrated significantly
      lower graft survival rates than did those without proteinuria (48.3% versus
      51.7%, respectively; P = 0.017; Risk Ratio = 0.403; 95% confidence interval 0.188
      0.862). We conclude that proteinuria is prevalent after kidney transplant in our
      population, and that it is most commonly associated with chronic allograft
      nephropathy, transplant glomerulopathy, glomerulonephritis and acute rejection.
      Post-transplant proteinuria is associated with decreased allograft survival. 

PMID- 25579743
TI  - Spectrum of intradialytic complications during hemodialysis and its management: a
      single-center experience.
AB  - Hemodialysis (HD) is one of the important modalities of renal replacement therapy
      in acute renal failure (ARF) as well as chronic renal failure (CRF). This study
      was performed to evaluate the various intradialytic complications that occur
      during HD and their management. This is a retrospective study performed in
      patients who underwent conventional HD during the period of 1 January 2000 to 31
      December 2011 at our center. Clinical details, various complications faced and
      their management were retrieved from dialysis case sheets. A total of 2325
      patients of renal failure (790 ARF and 1535 CRF patients) were assessed for the
      intradialytic complications of HD. During the study period, there were 12,785
      bicarbonate dialyses performed on these patients. In the ARF patients, the common
      intradialytic complications were: Hypotension, seen in 1296 sessions (30.4%),
      nausea and vomiting seen in 1125 sessions (26.4%), fever and chills seen in 818
      sessions (19.2%), headache seen in 665 sessions (15.6%), cramps seen in 85
      sessions (2.0%), chest pain and back pain seen in 82 sessions (1.92%),
      hypoglycemia seen in 77 sessions (1.8%), first-use syndrome seen in 72 sessions
      (1.7%) and femoral hematoma seen in 31 sessions (0.73%). In the CRF group, common
      complications were hypotension in 2230 sessions (26.1%), nausea and vomiting in
      1211 sessions (14.2%), fever and chills in 1228 sessions (14.4%), chest pain and
      back pain in 1108 cases (13.0%), hypertension in 886 sessions (10.4%), headache
      in 886 sessions (10.4%), cramps in 256 sessions (3.0%), hematoma in 55 sessions
      (0.64%), intracerebral hemorrhage in three sessions (0.03%) and catheter tip
      migration in three sessions (0.03%). There is a need for special attention for
      the diagnosis and management of intradialytic complications of HD because such
      complications could be managed successfully without the need for termination of
      the dialysis procedure. 

PMID- 25579744
TI  - Focal and segmental glomerulosclerosis: does prognosis vary with the variants?
AB  - Focal and segmental glomerulosclerosis (FSGS) is a clinicopathological entity.
      The following five FSGS variants: Collapsing, cellular, glomerular tip, peri
      hilar and not otherwise specified (NOS) are recognized, which may have prognostic
      value. The aim of this study was to highlight the clinical course and outcome in
      the different pathological variants of FSGS and to evaluate the predictive risk
      factors of end-stage renal disease (ESRD). It was a retrospective analysis of
      biopsy-proven primary FSGS patients who presented over a period of three years.
      The data were collected from the clinical and biopsy records of the Nephrology
      Unit. There were 116 patients with biopsy-proven FSGS. The frequency of
      occurrence of FSGS among all cases of the nephrotic syndrome seen in our unit was
      35.47%. NOS was the most common pathological variant (62.2%), followed by peri
      hilar (11.2%), cellular (9.4%) and glomerular tip (7.7%), and the least common
      variant was collapsing (4.3%). Majority of patients with collapsing, NOS and
      glomerular tip variants had nephrotic range proteinuria. However, the amount of
      proteinuria was highest in the glomerular tip and collapsing variants. A higher
      percentage of patients with the collapsing and cellular variants had renal
      failure at the time of presentation. A higher rate of tubular and interstitial
      changes was seen in the collapsing and cellular variants. The collapsing and
      cellular variants showed lower response rate and higher rates of ESRD, while the
      glomerular tip lesion had the highest remission rate and the lowest rate of ESRD.
      Poor prognostic factors for ESRD in FSGS were initial renal insufficiency, severe
      tubulo-interstitial change, initial nonresponsiveness to steroids and collapsing
      histopathological variant. Our study suggests that histopathological
      classification of FSGS is of paramount importance in the management and in
      predicting the prognosis. 

PMID- 25579747
TI  - Subjective evidence based ethnography: method and applications.
AB  - Subjective Evidence Based Ethnography (SEBE) is a method designed to access
      subjective experience. It uses First Person Perspective (FPP) digital recordings
      as a basis for analytic Replay Interviews (RIW) with the participants. This
      triggers their memory and enables a detailed step by step understanding of
      activity: goals, subgoals, determinants of actions, decision-making processes,
      etc. This paper describes the technique and two applications. First, the analysis
      of professional practices for know-how transferring purposes in industry is
      illustrated with the analysis of nuclear power-plant operators' gestures. This
      shows how SEBE enables modelling activity, describing good and bad practices,
      risky situations, and expert tacit knowledge. Second, the analysis of full days
      lived by Polish mothers taking care of their children is described, with a
      specific focus on how they manage their eating and drinking. This research has
      been done on a sub-sample of a large scale intervention designed to increase
      plain water drinking vs sweet beverages. It illustrates the interest of SEBE as
      an exploratory technique in complement to other more classic approaches such as
      questionnaires and behavioural diaries. It provides the detailed "how" of the
      effects that are measured at aggregate level by other techniques. 

PMID- 25579748
TI  - Single-stage operation using hypothermic circulatory arrest to remove uterine
      intravenous leiomyomatosis extended to the vena cava and right atrium.

PMID- 25579749
TI  - Impact of the introduction of neuraxial labor analgesia on mode of delivery at an
      urban maternity hospital in China.
AB  - OBJECTIVE: To evaluate the association between the introduction of neuraxial
      (epidural) labor analgesia and mode of delivery in a large urban maternity
      hospital in China. METHODS: A single-intervention impact study was conducted at
      Shijiazhuang Obstetrics and Gynecology Hospital in Shijiazhuang. Baseline data
      collection occurred between August 1 and December 31, 2009, when no analgesic
      method was routinely employed during labor. An intervention was then implemented,
      consisting of a neuraxial labor analgesia service. The service was fully
      operational from September 1, 2010, and data were collected to August 31, 2011.
      The mode of delivery was compared between the different periods. RESULTS:
      Neuraxial analgesia rate was used in none of the 3787 deliveries during the
      baseline period and 3429 (33.5%) of 10 230 in the implementation period.
      Cesareans were performed in 1533 (40.5%) deliveries in the baseline period and
      3441 (33.6%) in the implementation period (difference -6.8%, 99.8% confidence
      interval [CI] -9.7% to -3.9%; P<0.0017). The proportion of vaginal deliveries in
      which forceps were used was unchanged (difference -0.8%, 99.8% CI -0.7% to 2.2%;
      P=0.92). CONCLUSION: The introduction of epidural analgesia reduced the frequency
      of cesarean delivery, which improved obstetric and neonatal outcomes.

PMID- 25579750
TI  - Analysis of hysterectomies for patients with uterine leiomyomas in China in 2010.
AB  - OBJECTIVE: To analyze surgical methods and medical costs for patients with
      uterine leiomyomas treated by hysterectomy in mainland China in 2010. METHODS: In
      a cross-sectional study, data for patients hospitalized with uterine leiomyomas
      and treated with hysterectomy were obtained from pooled medical records of 3030
      hospitals. Type of surgery was categorized into abdominal hysterectomy (AH),
      laparoscopic hysterectomy (LH), and total vaginal hysterectomy (TVH). Length of
      stay and medical costs were analyzed for each procedure and in four types of
      hospital. RESULTS: Among 147 966 patients, 129 668 (87.6%) underwent AH, 9164
      (6.2%) LH, and 9134 (6.2%) TVH. The total cost and operative cost were lowest for
      the AH group and highest for the LH group (P<0.001). Length of stay was shortest
      for TVH groups in all four types of hospital (P<0.001). The ratios between the
      frequencies of the three procedures were significantly different among the four
      types of hospital (P<0.001). CONCLUSION: In mainland China, AH remains the main
      surgical route of hysterectomy for patients with uterine leiomyomas. The length
      of stay was shortest among patients undergoing TVH, but the mean stay was still
      more than 9days.

PMID- 25579745
TI  - Proinsulin misfolding and endoplasmic reticulum stress during the development and
      progression of diabetes.
AB  - To maintain copious insulin granule stores in the face of ongoing metabolic
      demand, pancreatic beta cells must produce large quantities of proinsulin, the
      insulin precursor. Proinsulin biosynthesis can account for up to 30-50% of total
      cellular protein synthesis of beta cells. This puts pressure on the beta cell
      secretory pathway, especially the endoplasmic reticulum (ER), where proinsulin
      undergoes its initial folding, including the formation of three evolutionarily
      conserved disulfide bonds. In normal beta cells, up to 20% of newly synthesized
      proinsulin may fail to reach its native conformation, suggesting that proinsulin
      is a misfolding-prone protein. Misfolded proinsulin molecules can either be
      refolded to their native structure or degraded through ER associated degradation
      (ERAD) and autophagy. These degraded molecules decrease proinsulin yield but do
      not otherwise compromise beta cell function. However, under certain pathological
      conditions, proinsulin misfolding increases, exceeding the genetically determined
      threshold of beta cells to handle the misfolded protein load. This results in
      accumulation of misfolded proinsulin in the ER - a causal factor leading to beta
      cell failure and diabetes. In patients with Mutant INS-gene induced diabetes of
      Youth (MIDY), increased proinsulin misfolding due to insulin gene mutations is
      the primary defect operating as a "first hit" to beta cells. Additionally,
      increased proinsulin misfolding can be secondary to an unfavorable ER folding
      environment due to genetic and/or environmental factors. Under these conditions,
      increased wild-type proinsulin misfolding becomes a "second hit" to the ER and
      beta cells, aggravating beta cell failure and diabetes. In this article, we
      describe our current understanding of the normal proinsulin folding pathway in
      the ER, and then review existing links between proinsulin misfolding, ER
      dysfunction, and beta cell failure in the development and progression of type 2,
      type 1, and some monogenic forms of diabetes. 

PMID- 25579746
TI  - Immunogenetics of type 1 diabetes mellitus.
AB  - Type 1 diabetes mellitus (T1DM) is an autoimmune disease arising through a
      complex interaction of both genetic and immunologic factors. Similar to the
      majority of autoimmune diseases, T1DM usually has a relapsing remitting disease
      course with autoantibody and T cellular responses to islet autoantigens, which
      precede the clinical onset of the disease process. The immunological diagnosis of
      autoimmune diseases relies primarily on the detection of autoantibodies in the
      serum of T1DM patients. Although their pathogenic significance remains uncertain,
      they have the practical advantage of serving as surrogate biomarkers for
      predicting the clinical onset of T1DM. Type 1 diabetes is a polygenic disease
      with a small number of genes having large effects (i.e. HLA), and a large number
      of genes having small effects. Risk of T1DM progression is conferred by specific
      HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3) or DRB1*04-DQB1*0302 (DR4)]. In
      addition, HLA alleles such as DQB1*0602 are associated with dominant protection
      from T1DM in multiple populations. A discordance rate of greater than 50% between
      monozygotic twins indicates a potential involvement of environmental factors on
      disease development. Viral infections may play a role in the chain of events
      leading to disease, albeit conclusive evidence linking infections with T1DM
      remains to be firmly established. Two syndromes have been described in which an
      immune-mediated form of diabetes occurs as the result of a single gene defect.
      These syndromes are termed autoimmune polyglandular syndrome type I (APS-I) or
      autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), and X
      linked poyendocrinopathy, immune dysfunction and diarrhea (XPID). These two
      syndromes are unique models to understand the mechanisms involved in the loss of
      tolerance to self-antigens in autoimmune diabetes and its associated organ
      specific autoimmune disorders. A growing number of animal models of these
      diseases have greatly helped elucidate the immunologic mechanisms leading to
      autoimmune diabetes. 

PMID- 25579752
TI  - A systematic review of factors influencing older adults' decision to accept or
      decline cancer treatment.
AB  - BACKGROUND: Cancer is a disease that affects mostly older adults. Older adults
      often have other chronic health conditions in addition to cancer and may have
      different health priorities, both of which can impact cancer treatment decision
      making. However, no systematic review of factors that influence an older cancer
      patient's decision to accept or decline cancer treatment has been conducted.
      MATERIALS AND METHODS: Systematic review of the literature published between
      inception of the databases and February 2013. Dutch, English, French or German
      articles reporting on qualitative studies, cross-sectional, longitudinal
      observational or intervention studies describing factors why older adults
      accepted or declined cancer treatment examining actual treatment decisions were
      included. Ten databases were used. Two independent reviewers reviewed manuscripts
      and performed data abstraction using a standardized form and the quality of
      studies was assessed with the Mixed Methods Appraisal Tool. RESULTS: Of 17,343
      abstracts reviewed, a total of 38 studies were included. The majority focused on
      breast and prostate cancer treatment decisions and most studies used a
      qualitative design. Important factors for accepting treatment were convenience
      and success rate of treatment, seeing necessity of treatment, trust in the
      physician and following the physician's recommendation. Factors important for
      declining cancer treatment included concerns about the discomfort of the
      treatments, fear of side effects and transportation difficulties. CONCLUSION:
      Although the reasons why older adults with cancer accepted or declined treatment
      varied considerably, the most consistent determinant was physician
      recommendation. Further studies using large, representative samples and exploring
      decision-making incorporating health literacy and comorbidity are needed.

PMID- 25579751
TI  - Amyloid deposits and inflammatory infiltrates in sporadic inclusion body
      myositis: the inflammatory egg comes before the degenerative chicken.
AB  - Sporadic inclusion body myositis (sIBM) is the most frequently acquired myopathy
      in patients over 50 years of age. It is imperative that neurologists and
      rheumatologists recognize this disorder which may, through clinical and
      pathological similarities, mimic other myopathies, especially polymyositis.
      Whereas polymyositis responds to immunosuppressant drug therapy, sIBM responds
      poorly, if at all. Controversy reigns as to whether sIBM is primarily an
      inflammatory or a degenerative myopathy, the distinction being vitally important
      in terms of directing research for effective specific therapies. We review here
      the pros and the cons for the respective hypotheses. A possible scenario, which
      our experience leads us to favour, is that sIBM may start with inflammation
      within muscle. The rush of leukocytes attracted by chemokines and cytokines may
      induce fibre injury and HLA-I overexpression. If the protein degradation systems
      are overloaded (possibly due to genetic predisposition, particular HLA-I subtypes
      or ageing), amyloid and other protein deposits may appear within muscle fibres,
      reinforcing the myopathic process in a vicious circle.

PMID- 25579754
TI  - Evaluation of rhBMP-2/collagen/TCP-HA bone graft with and without bone marrow
      cells in the canine femoral multi defect model.
AB  - Recombinant human bone morphogenetic protein-2, when applied to an absorbable
      type 1 bovine collagen sponge (rhBMP-2/ACS) is an effective therapy in many bone
      grafting settings. Bone marrow aspirate (BMA) has also been used as a source of
      transplantable osteogenic connective tissue progenitors. This study was designed
      to characterize the performance of a scaffold comprising rhBMP-2/ACS in which the
      sponge wraps around tri-calcium phosphate hydroxyapatite granules (rhBMP
      2/ACS/TCP-HA) and to test the hypothesis that addition of BMA will improve the
      performance of this construct in the Canine Femoral Multi Defect Model. In each
      subject, two sites were grafted with rhBMP-2/ACS/TCP-HA scaffold loaded with BMA
      clot and two other sites with rhBMP-2/ACS/TCP-HA scaffold loaded with wound blood
      (WB). After correction for unresorbed TCP-HA granules, sites grafted with rhBMP
      2/ACS/TCP-HA+BMA and rhBMP-2/ACS/TCP-HA+WB were similar, with mean percent bone
      volumes of 10.9 %+/-1.2 and 11.2 %+/-1.2, respectively. No differences were seen
      in quantitative histomorphometry. While bone formation using both constructs was
      robust, this study did not support the hypothesis that the addition of
      unprocessed bone marrow aspirate clot improved bone regeneration in a site
      engrafted with rhBMP-2/ACS/TCP-HA+BMA. In contrast to prior studies using this
      model, new bone formation was greater at the center of the defect where TCP-HA
      was distributed. This finding suggests a potential synergy between rhBMP-2 and
      the centrally placed ceramic and cellular components of the graft construct.
      Further optimization may also require more uniform distribution of TCP-HA,
      alternative cell delivery strategies, and a more rigorous large animal segmental
      defect model.

PMID- 25579753
TI  - Drug radiotherapy combinations: review of previous failures and reasons for
      future optimism.
AB  - Combining chemotherapy with radiotherapy has resulted in significant clinical
      improvements in many different tumour types. However, the non-specific mechanisms
      by which these drugs exert their effects mean that this is often at the expense
      of increased side effects. Previous attempts at using targeted drugs to induce
      more tumour specific radiosensitisation have been generally disappointing.
      Although cetuximab, an EGFR monoclonal antibody, resulted in improved overall
      survival in HNSCC when combined with radiotherapy, it has failed to show benefit
      when added to chemo-radiotherapy. In addition, our inability to successfully use
      drug treatments to reverse tumour hypoxia is underlined by the fact that no such
      treatment is currently in widespread clinical use. The reasons for these failures
      include the lack of robust biomarkers, and the previous use of drugs with
      unacceptable side-effect profiles. Despite these disappointments, there is reason
      for optimism. Our improved understanding of key signal transduction pathways and
      of tumour specific DNA repair deficiencies has produced new opportunities to
      specifically radiosensitise tumours. Novel strategies to reduce tumour hypoxia
      include the use of drugs that cause vascular normalisation and drugs that reduce
      tumour oxygen consumption. These new strategies, combined with better compounds
      at our disposal, and an ability to learn from our previous mistakes, mean that
      there is great promise for future drug-radiotherapy combinations to result in
      significant clinical benefits. 

PMID- 25579755
TI  - Injectable microcarriers as human mesenchymal stem cell support and their
      application for cartilage and degenerated intervertebral disc repair.
AB  - Degeneration of the intervertebral disc (IVD) is a progressive and chronic
      process, and the high incidence of discogenic disorders calls for new therapeutic
      approaches, such as cell-based therapies using three dimensional cultures and
      mesenchymal stem cells (MSC), which can differentiate to chondrogenic- and IVD
      lineages. Here, we investigated the growth and differentiation of human MSC
      culture on biodegradable collagen scaffolds in order to obtain an injectable
      suspension. Commercially available wound dressings were downsized to dimensions
      between 100 and 1500 MUm and seeded with freshly isolated or early passages MSC.
      Proliferation rate and chondrogenic differentiation potential was tested at
      oxygenation levels of 2%, 5%, 10% and 21% in static and dynamic cultures.
      Evaluation methods included cell viability test, disc marker genes expression
      (aggrecan, collagen type I and type II), histological detection of proteoglycans
      and immunohistochemical analysis. On microcarriers, freshly isolated MSC had
      lower proliferation rate and chondrogenic differentiation potential compared with
      early passages MSC. Proliferation of MSC was significantly increased 1.7-fold at
      5% oxygen level and in combination with dynamic culture was further increased to
      2.3-fold, with respect to normoxia. Chondrogenesis was positively affected by 2%
      and 5% hypoxia, as shown by increased transcription levels and protein expression
      of collagen type II and proteoglycan accumulation in static cultures, while it
      was inhibited in dynamic cultures. Collagen type I and aggrecan expression were
      not affected by hypoxia. In conclusion, collagen based microcarriers are a
      suitable support for in vitro MSC growth and chondrogenesis especially when
      cultured at 5% oxygen level.

PMID- 25579756
TI  - Antibiotic treatment as sole management of Helicobacter pylori-negative gastric
      MALT lymphoma: a single center experience with prolonged follow-up.
AB  - Relatively little is known about the long-term outcome of patients with
      Helicobacter pylori (HP)-negative gastric lymphoma of mucosa-associated lymphoid
      tissue (MALT lymphoma) with antibiotic therapy as sole management. We have
      analyzed all patients with HP-negative gastric MALT lymphoma undergoing
      antibiotic therapy as sole management of their disease. HP negativity was defined
      as negative histology, breath test and serology, and response to treatment,
      survival and long-term outcome was assessed together with clinico-pathological
      characteristics including t(11; 18) (q21; q21) translocation. Out of 97 patients
      with gastric MALT lymphoma, 24 were HP-negative, and 13 (5 females and 8 males)
      underwent only antibiotic management for initial therapy. Eight had stage I and
      five were found to have stage II disease, with three patients suffering from an
      underlying autoimmune disease. Antibiotic therapy consisted of standard HP
      eradication regimens consisting of clarithromycin in all patients, along with
      metronidazole in seven and amoxicillin in six plus a proton-pump inhibitor. After
      a median follow-up of 95 months (42-, 181+), 12/13 patients are alive. Six
      patients with stage I disease achieved an objective response (five complete (CR)
      and one partial remission, 46 %), four had stable disease (lasting 11-27 months),
      and three progressed. All patients with stable disease received chemotherapy, but
      only one patient due to clear cut progression. One patient relapsed 23 months
      after initial CR, and achieved a second CR with antibiotics now lasting 87
      months. These results indicate that a relevant percentage of patients with HP
      negative gastric MALT lymphoma may benefit from antibiotic therapy and do not
      require additional oncological therapies. Our data suggest that the remissions
      seen in these patients might be durable as evidenced by prolonged follow-up in
      our series. 

PMID- 25579757
TI  - Herbal dietary supplement associated hepatotoxicity: an upcoming workshop and
      need for research.

PMID- 25579758
TI  - Apocynum venetum leaf attenuates myocardial ischemia/reperfusion injury by
      inhibiting oxidative stress.
AB  - Apocynum venetum, a Chinese medicinal herb, is reported to be neuroprotective.
      However, whether Apocynum venetum leaf extract (AVLE) protects against ischemic
      myocardium remains elusive. Our present study was aimed to observe the effects of
      AVLE preconditioning on myocardial ischemia/reperfusion (MI/R) injury and to
      investigate the possible mechanisms. Rats were treated with AVLE (500 mg/kg/d,
      o.g.) or distilled water once daily for one week. Afterward, all the animals were
      subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. AVLE
      preconditioning for one week significantly improved cardiac function following
      MI/R. Meanwhile, AVLE reduced infarct size, plasma creatine kinase (CK)/lactate
      dehydrogenase (LDH) activities and myocardial apoptosis at the end of reperfusion
      in rat hearts. Moreover, AVLE preconditioning significantly inhibited superoxide
      generation, gp91(phox) expression, malonaldialdehyde formation and enhanced
      superoxide dismutase (SOD) activity in I/R hearts. Furthermore, AVLE treatment
      increased Akt and extracellular regulated protein kinases 1/2 (ERK1/2)
      phosphorylations in I/R rat heart. Either the Phosphatidylinositide 3-kinase
      (PI3K) inhibitor wortmannin or the ERK1/2 inhibitor PD98059 blocked AVLE
      stimulated anti-oxidative effects and cardioprotection. Our study demonstrated
      for the first time that AVLE reduces oxidative stress and exerts cardioprotection
      against MI/R injury in rats. 

PMID- 25579759
TI  - Traditional Chinese medicine formulas for irritable bowel syndrome: from ancient
      wisdoms to scientific understandings.
AB  - Traditional Chinese Medicine (TCM) serves as the most common alternative
      therapeutic approach for Western medicine and benefits IBS patients globally. Due
      to the lack of scientific evidence in the past, TCM formulas were not
      internationally well recognized as promising IBS remedies. In this review,
      firstly, we present the etiology and therapy of IBS in terms of traditional
      Chinese medical theory. Secondly, we summarize the clinical randomized controlled
      trials (RCTs) of TCM formulas for IBS patients that are available in the
      literature (from 1998 to September 2013), in which 14 RCTs conducted of high
      quality were discussed in detail. Of the 14 selected trials, 12 of those
      concluded that TCM formulas provided superior improvement in the global symptoms
      of IBS patients over the placebo or conventional medicines. As well, all 14 RCTs
      suggested that TCM formulas have good safety and tolerability. Last but not
      least, we explore the pharmacological mechanisms of the anti-IBS TCM formulas
      available in the literature (from 1994 to September, 2013). Collectively, in
      combating IBS symptoms, most TCM formulas exert multi-targeting actions including
      the regulation of neurotransmitters and hormones in the enteric nervous system
      (ENS), modulation of smooth muscle motility in the gastrointestinal (GI) tract,
      modulation of the hypothalamic-pituitary-adrenal (HPA) axis, attenuation of
      intestinal inflammation and restoration of intestinal flora, etc. In conclusion,
      TCM formulas appear to be promising for IBS treatment. This review provides a
      useful reference for the public in furthering a better understanding and
      acceptance of TCM formulas as IBS remedies. 

PMID- 25579760
TI  - Erratum to "a network and visual quality aware N-screen content recommender
      system using joint matrix factorization".
AB  - [This corrects the article DOI: 10.1155/2014/806517.]. 

PMID- 25579761
TI  - The platelet P2 receptors in inflammation.
AB  - In addition to their well characterized and established role in haemostasis and
      thrombosis, platelets contribute to the pathogenesis of inflammation. Adenine
      nucleotides are signalling molecules that regulate the function of virtually
      every cell in the body, by interacting with P2 receptors. Their important role in
      inflammation is well established. In the last few years, the pro-inflammatory
      roles of adenine nucleotides interacting with their platelet P2 receptors has
      emerged. In particular, it was shown that the platelet P2Y12 receptor for ADP
      significantly contributed to the pro-inflammatory effects of cysteinyl
      leukotrienes (CysLT) in experimental models of asthma in mice. More importantly,
      it was recently shown that P2Y12 variants were associated with lung function in a
      large family-based asthma cohort and that the P2Y12 antagonist prasugrel tended
      to decrease bronchial hyper-reactivity to mannitol in patients with allergic
      bronchial asthma in a randomized, placebo controlled trial. CONCLUSION: These
      data strongly suggest that P2Y12 may represent an important pharmacological
      target for the treatment of patients with allergic bronchial asthma.

PMID- 25579768
TI  - Securing the future of interventional radiology with lessons from the past.

PMID- 25579769
TI  - A preserved stratified pattern of the bowel wall 1 year after major surgery does
      not influence the surgical recurrence of Crohn's disease.

PMID- 25579770
TI  - Surface charging behavior of nanoparticles by considering site distribution and
      density, dielectric constant and pH changes--a Monte Carlo approach.
AB  - Monte Carlo simulations are used to describe the charging behavior of metal oxide
      nanoparticles thus enabling a novel and original approach to predict nanoparticle
      reactivity and the possible interactions with biological and environmental
      molecules. The charging behavior of spherical nanoparticles is investigated by
      adjusting the pH of the media and the influence of surface site distribution,
      density and dielectric constant as well as the acid/base properties of the
      surface sites and DeltapKa(0) values (difference between two successive
      deprotonation constants) is systematically studied using a grand canonical Monte
      Carlo method. A primitive Coulomb model is applied to describe the interaction
      energies between the explicit discrete sites. Homogeneous/heterogeneous surfaces
      and patches with homogeneous and heterogeneous distributions are considered in
      order to reproduce possible site distributions of metal oxide nanoparticles. Two
      models are used. In the 1-pKa(0) model (one deprotonation step) the results
      indicate that the deprotonation process is controlled by inter-site distances
      which are defined by site distributions and densities. It is shown that the
      homogeneous surface is the most efficient site distribution to obtain high
      ionization degrees. In the 2-pKa(0) model (two deprotonation steps), the
      DeltapKa(0) value is found to control the surface charge properties with regard
      to pH changes. By considering the variation of the total nanoparticle surface
      charge as a function of pH our results help in the distinction between the zero
      charge and the isoelectric point and interpretation of experimental NP titration
      curves.

PMID- 25579771
TI  - [Intravenous ferric carboxymaltose-associated hypophosphatemia in patients with
      iron deficiency anemia. A common side effect].
AB  - OBJECTIVES: To determine the frequency, severity, time of onset and factors
      associated with the development of hypophosphatemia (HF) in patients with iron
      deficiency anemia treated with intravenous ferric carboxymatose (ivFCM). MATERIAL
      AND METHODS: Retrospective cohort study in patients iron deficiency anemia who
      received ivFCM and had an a prior and subsequent determination of serum
      phosphate. We carried out a comparative analysis between baseline and post-ivFCM
      levels of serum phosphate. In order to identify variables independently
      associated with HF a logistic regression analysis was also performed. RESULTS:
      One hundred twenty-five patients were included. HF frequency was 58%. The median
      time to onset of HF was 18 days. Age, baseline ferritin levels and baseline
      phosphate levels were independently associated with the development of HF. The
      risk of HF in patients with baseline phosphate levels <= 3.1mg/dl was 67% higher
      than patients with >= 3.7 mg/dl. CONCLUSIONS: ivFCM-associated HF is a frequent,
      early and, sometimes, prolonged effect in patients with iron deficiency anemia.
      Serum phosphate levels should be monitored after ivFCM administration, especially
      in older patients and in those with lower baseline phosphate or ferritin levels.

PMID- 25579772
TI  - [Management of furuncle, furunculosis and anthrax].

PMID- 25579773
TI  - [Delta0-thalassemia by insertion of 27 base pairs in delta-globin gene with
      decreased hemoglobin A2 levels].
AB  - BACKGROUND AND OBJECTIVE: We describe a novel delta-thalassemia mutation causing
      decreased hemoglobin (Hb) A2 levels associated with Hb Watts, variant Hb
      resulting from a trinucleotide deletion in Spain. PATIENTS AND METHOD: Hb variant
      analysis was performed by cation-exchange high performance liquid chromatography
      (HPLC) and capillary zone electrophoresis. Polymerase chain reaction and DNA
      sequence analyses were used to identify mutations in the delta- and alpha-globin
      genes. RESULTS: Abnormal Hb was observed on capillary zone electrophoresis in Z6
      and by cation-exchange HPLC a slower peak than HbA was observed at an retention
      time of 4.19min. This variant Hb is called Hb Watts [alpha2 74(EF3)Asp->0 or
      alpha2 75(EF4)Asp->0; HBA2:c.226_228delGAC]. The decreased HbA2 percentage owes
      to an insertion of 27nt between nt 83 and 84 of IVS-I of the delta-globin gene.
      CONCLUSIONS: When analyzing a chromatogram, the possibility of the existence of
      delta-thalassemia or an HbA2 variant should be considered, apart from alfa-, beta
      thalassemia and structural haemoglobinopathies. To this end, each of the peaks
      and their percentages should be considered to allow for correct interpretation
      and to avoid misdiagnosis as much as possible.

PMID- 25579774
TI  - [Mycobacterium avium complex infection detected by bone marrow aspiration in a
      human immunodeficiency virus infected patient].

PMID- 25579775
TI  - [Sarcoidosis-lymphoma syndrome].

PMID- 25579776
TI  - Conducting additive-free amorphous GeO2/C composite as a high capacity and long
      term stability anode for lithium ion batteries.
AB  - In this study, a novel method has been proposed for synthesizing amorphous GeO2/C
      composites. The amorphous GeO2/C composite without carbon black as an electrode
      for Li-ion batteries exhibited a high specific capacity of 914 mA h g(-1) at the
      rate of C/2 and enhanced rate capability. The amorphous GeO2/C electrode
      exhibited excellent electrochemical stability with a 95.3% charge capacity
      retention after 400 charge-discharge cycles, even at a high current charge
      discharge of C/2. Furthermore, a full cell employing the GeO2/C anode and the
      LiCoO2 cathode displayed outstanding cycling performance. The superior
      performance of the GeO2/C electrode enables the amorphous GeO2/C to be a
      potential anode material for secondary Li-ion batteries. 

PMID- 25579777
TI  - Lack of effectiveness of the 23-valent polysaccharide pneumococcal vaccine in
      reducing all-cause pneumonias among healthy young military recruits: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Streptococcus pneumoniae infections have periodically caused
      significant morbidity and outbreaks among military personnel, especially
      trainees. This study evaluated the effectiveness of the 23-valent polysaccharide
      pneumococcal vaccine (PPV23) in reducing pneumonia in healthy military trainees.
      METHODS: From 2000-2003, 152723 military trainees from 5 US training camps were
      enrolled in a double-blind, placebo-controlled trial of PPV23. Participants were
      closely monitored during basic training for radiographically confirmed pneumonia
      etiology and loss-of-training days. Participants were also followed using
      electronic medical encounter data until 1 June 2007 for three additional
      outcomes: any-cause pneumonia, any acute respiratory disease, and meningitis.
      RESULTS: Comparison of demographic data by study arm suggested the randomization
      procedures were sound. During basic training, 371 study participants developed
      radiographically confirmed pneumonia. None had evidence of S. pneumoniae
      infection, but other etiologies included adenovirus (38%), Chlamydophila
      pneumoniae (9%), and Mycoplasma pneumoniae (8%). During the follow-up period,
      many study participants, in both the vaccine and placebo groups, had clinical
      encounters for the medical outcomes of interest. However, Cox's proportional
      hazard modeling revealed no evidence of a protective vaccine effect during
      recruit training (radiographically confirmed pneumonia) or up to 6.7 years after
      enrollment (any-cause pneumonia, any acute respiratory disease, or meningitis).
      CONCLUSIONS: Data from this large, double-blind, placebo controlled trial do not
      support routine use of PPV23 among healthy new military trainees. This clinical
      trial was registered at clinicaltrials.gov (registration number NCT02079701,
      http://www.clinicaltrials.gov/ct2/show/NCT02079701?term=NCT02079701&rank=1).

PMID- 25579778
TI  - [FeFe]-hydrogenase oxygen inactivation is initiated at the H cluster 2Fe
      subcluster.
AB  - The [FeFe]-hydrogenase catalytic site H cluster is a complex iron sulfur cofactor
      that is sensitive to oxygen (O2). The O2 sensitivity is a significant barrier for
      production of hydrogen as an energy source in water-splitting, oxygenic systems.
      Oxygen reacts directly with the H cluster, which results in rapid enzyme
      inactivation and eventual degradation. To investigate the progression of O2
      dependent [FeFe]-hydrogenase inactivation and the process of H cluster
      degradation, the highly O2-sensitive [FeFe]-hydrogenase HydA1 from the green
      algae Chlamydomonas reinhardtii was exposed to defined concentrations of O2 while
      monitoring the loss of activity and accompanying changes in H cluster
      spectroscopic properties. The results indicate that H cluster degradation
      proceeds through a series of reactions, the extent of which depend on the initial
      enzyme reduction/oxidation state. The degradation process begins with O2
      interacting and reacting with the 2Fe subcluster, leading to degradation of the
      2Fe subcluster and leaving an inactive [4Fe-4S] subcluster state. This final
      inactive degradation product could be reactivated in vitro by incubation with 2Fe
      subcluster maturation machinery, specifically HydF(EG), which was observed by
      recovery of enzyme activity. 

PMID- 25579779
TI  - Critical insights into the beneficial and protective actions of the kallikrein
      kinin system.
AB  - Hypertension is characterized by an imbalance between the renin-angiotensin
      system (RAS) and the kallikrein-kinin system (KKS). Angiotensin-converting enzyme
      inhibitors (ACEIs) and angiotensin II AT-1 receptor antagonists (also known as
      sartans or ARBs) are potent modulators of these systems and are highly effective
      as first-line treatments for hypertension, diabetic nephropathies, and diseases
      of the brain and coronary arteries. However, these agents are mechanistically
      distinct and should not be considered interchangeable. In this mini-review, we
      provide novel insights into the often neglected roles of the KKS in the
      beneficial, protective, and reparative actions of ACEIs. Indeed, ACEIs are the
      only antihypertensive drugs that properly reduce the imbalance between the RAS
      and the KKS, thereby restoring optimal cardiovascular homeostasis and
      significantly reducing morbidity and the risk of all-cause mortality among
      individuals affected by hypertension and other cardiovascular diseases.

PMID- 25579780
TI  - Exploring the 3 A's of cystectomy access to care for muscle-invasive bladder
      cancer.
AB  - Despite a known survival benefit, gross underutilization of radical cystectomy in
      the treatment of muscle-invasive bladder cancer (MIBC) continues. The leading
      hypothesis for these low utilization rates is access to care, with barriers that
      can be classified into 3 categories: acceptability, availability, and
      affordability. Acceptability is highlighted by patient miseducation, fears, and
      cultural beliefs, which can lead to poor treatment decisions and emphasizes the
      need for decision-making research for MIBC. Availability is defined by structural
      barriers such as facility type and physician access. Understanding and improving
      differences in treatment among community vs. academic centers may improve access
      to cystectomy among patients who are treated locally. Affordability is marked by
      both direct (e.g., hospital) and indirect (e.g., travel) costs, with insurance
      type and travel distance notably affecting cystectomy receipt. Understanding the
      interplay of the "3 A's" that comprise cystectomy access to care is needed before
      we can successfully increase utilization of cystectomy in the vulnerable MIBC
      population.

PMID- 25579781
TI  - Solution vs. gas phase relative stability of the choline/acetylcholine cavitand
      complexes.
AB  - How the information obtained from the gas phase experiments can reflect the
      processes in solution is a crucial question for analytical chemistry, and
      particularly the selective host-guest recognition mechanisms which are
      fundamental in biology. Here we combine ElectroSpray Ionization mass spectrometry
      (ESI-MS) and the Collision Induced Dissociation (CID) experiments to the density
      functional theory to investigate the interaction of acetylcholine and the choline
      cation with a triphosphonate cavitand. While the relative abundance of the cation
      complexes in the ESI mass spectrum reflects the preferential capture of the
      acetylcholine ion over the choline ion by the cavitand in the solution, the gas
      phase CID measurements indicate that after desolvation the choline cation is the
      most strongly bound to the host. The experimental results are interpreted by
      theory that underlines the role of the counterion in the stabilization of the
      complexes in solution and therefore in the selective recognition of substrates of
      biological interest. 

PMID- 25579785
TI  - A streamlined protocol for extracting RNA and genomic DNA from archived human
      blood and muscle.
AB  - We combined the TRIzol method of nucleic acid extraction with QIAamp columns to
      achieve coextraction of RNA and genomic DNA from peripheral blood mononuclear
      cells (PBMCs) and biopsied skeletal muscle, both stored at -80  degrees C for
      many months. Total RNA was recovered from the upper aqueous phase of TRIzol. The
      interphase and organic phases were precipitated with ethanol, digested with
      proteinase K, and filtered through QIAamp MinElute columns to recover DNA. The
      combined protocol yielded excellent quality and quantity of nucleic acids from
      archived human PBMCs and muscle and may be easily adapted for other tissues.

PMID- 25579787
TI  - The 2014 United States National Residency Match Program data for primary care
      programs: a review.
AB  - The paper focuses on the past five years of National Residency Match Program
      (NRMP) information in the Unites States with a comparison point of twenty years
      ago utilized because of a referenced article. It is well known to our students
      going through the match that it is more competitive than in prior years. To rank
      enough programs for your field, take Step 2 early to maximize your score, to get
      quality letters and to practice mock interviews. The 99% match rate has remained
      steady over the past five years despite an increase in all primary care
      disciplines particularly Internal Medicine. Family Medicine and Internal Medicine
      work with, on average, about half U.S. seniors and half from other groups
      including Osteopathic and IMG (U.S. citizen and non-U.S. citizen). This can
      create a holistic experience for residents with a sharing of ideas from students
      from varied backgrounds. While the Supplemental Offer and Acceptance Program
      appear as an initial success, the student's goal should be to avoid such a step
      altogether. The key twenty years ago and today is the existence of appropriate
      numbers of resident and faculty role models. This is a stressful goal considering
      the demands on faculty for billing and patient care due to the shiftwork nature
      of the new work hours. 

PMID- 25579786
TI  - Determination of hyaluronan molecular mass distribution in human breast milk.
AB  - Hyaluronan (HA) in human milk mediates host responses to microbial infection via
      TLR4- and CD44-dependent signaling. Signaling by HA is generally size specific.
      Because pure HA with average molecular mass (M) of 35 kDa can elicit a protective
      response in intestinal epithelial cells, it has been proposed that human milk HA
      may have a bioactive low-M component. Here we report the size distribution of HA
      in human milk samples from 20 unique donors. A new method for HA analysis,
      employing ion exchange (IEX) chromatography to fractionate HA by size and
      specific quantification of each size fraction by competitive enzyme-linked
      sorbent assay (ELSA), was developed. When separated into four fractions, milk HA
      with M?20 kDa, M~20 to 60 kDa, and M~60 to 110 kDa comprised averages of 1.5,
      1.4, and 2.0% of the total HA, respectively. The remaining 95% was HA with M?110
      kDa. Electrophoretic analysis of the higher M HA from 13 samples showed nearly
      identical M distributions, with an average M of approximately 440 kDa. This
      higher M HA component in human milk is proposed to bind to CD44 and to enhance
      human beta defensin 2 (HBD2) induction by the low-M HA components.

PMID- 25579788
TI  - A single dose of PPARgamma agonist pioglitazone reduces cortical oxidative damage
      and microglial reaction following lateral fluid percussion brain injury in rats.
AB  - Neuroprotective actions of the peroxisome proliferator-activated receptor-gamma
      (PPARgamma) agonists have been observed in various animal models of the brain
      injuries. In this study we examined the effects of a single dose of pioglitazone
      on oxidative and inflammatory parameters as well as on neurodegeneration and the
      edema formation in the rat parietal cortex following traumatic brain injury (TBI)
      induced by the lateral fluid percussion injury (LFPI) method. Pioglitazone was
      administered in a dose of 1mg/kg at 10min after the brain trauma. The animals of
      the control group were sham-operated and injected by vehicle. The rats were
      decapitated 24h after LFPI and their parietal cortices were analyzed by
      biochemical and histological methods. Cortical edema was evaluated in rats
      sacrificed 48h following TBI. Brain trauma caused statistically significant
      oxidative damage of lipids and proteins, an increase of glutathione peroxidase
      (GSH-Px) activity, the cyclooxygenase-2 (COX-2) overexpression, reactive
      astrocytosis, the microglia activation, neurodegeneration, and edema, but it did
      not influence the superoxide dismutase activity and the expressions of
      interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in the rat
      parietal cortex. Pioglitazone significantly decreased the cortical lipid and
      protein oxidative damage, increased the GSH-Px activity and reduced microglial
      reaction. Although a certain degree of the TBI-induced COX-2 overexpression,
      neurodegeneration and edema decrease was detected in pioglitazone treated rats,
      it was not significant. In the injured animals, cortical reactive astrocytosis
      was unchanged by the tested PPARgamma agonist. These findings demonstrate that
      pioglitazone, administered only in a single dose, early following LFPI, reduced
      cortical oxidative damage, increased antioxidant defense and had limited anti
      inflammatory effect, suggesting the need for further studies of this drug in the
      treatment of TBI. 

PMID- 25579789
TI  - Position 834 in TM6 plays an important role in cholesterol and
      phosphatidylcholine transport by ABCA1.
AB  - ATP-binding cassette protein A1 (ABCA1) plays a key role in eliminating excess
      cholesterol from peripheral cells by generating nascent high-density lipoprotein
      (HDL). However, it remains unclear whether both phospholipids and cholesterol are
      directly loaded onto apolipoprotein A-I (apoA-I) by ABCA1. To identify the amino
      acid residues of ABCA1 involved in substrate recognition and transport, we
      applied arginine scan mutagenesis to residues L821-E843 of human ABCA1 and
      predicted the environment to which each residue is exposed. The relative surface
      expression of each mutant suggested that residues L821-E843 pass through the
      plasma membrane as TM6, and the four residues (S826, F830, L834, and V837) of TM6
      are exposed to the hydrophilic internal cavity of ABCA1. Furthermore, we showed
      that L834 is critical for the function of ABCA1. 

PMID- 25579796
TI  - The promotion effect of surface negative electrostatic field on the
      photogenerated charge separation of BiVO4 and its contribution to the enhanced
      PEC water oxidation.
AB  - The increased surface-carried negative charge of BiVO4 after phosphate
      modification prolongs the photogenerated charge carrier lifetime and improves the
      separation by inducing the holes to transfer to the surface, leading to the
      obvious enhancement of visible light activities for PEC water oxidation. 

PMID- 25579797
TI  - FT-IR and FT-Raman spectroscopic signatures, vibrational assignments, NBO, NLO
      analysis and molecular docking study of 2-{[5-(adamantan-1-yl)-4-methyl-4H-1,2,4
      triazol-3-yl]sulfanyl}-N,N-dimethylethanamine.
AB  - FT-Raman and FT-IR spectra of the title compound 2-{[5-(adamantan-1-yl)-4-methyl
      4H-1,2,4-triazol-3-yl]sulfanyl}-N,N-dimethylethanamine were recorded and
      investigated. The DFT/B3LYP/6-311++G(d,p) method was used to compute the
      vibrational wavenumbers. A good coherence between experimental and theoretical
      wavenumbers shows the preciseness of the assignments. NLO properties like the
      dipole moment, polarizability, first static hyperpolarizability, molecular
      electrostatic potential surface and contour map have been calculated to get a
      better cognizance of the properties of the title molecule. Natural bond orbital
      analysis has been applied to estimate the stability of the molecule arising from
      charge delocalization. The molecular docking studies concede that title compound
      may exhibit HIV-1 Protease 1N49 inhibitory activity. 

PMID- 25579795
TI  - The RIG-I-like helicase receptor MDA5 (IFIH1) is involved in the host defense
      against Candida infections.
AB  - The induction of host defense against Candida species is initiated by recognition
      of the fungi by pattern recognition receptors and activation of downstream
      pathways that produce inflammatory mediators essential for infection clearance.
      In this study, we present complementary evidence based on transcriptome analysis,
      genetics, and immunological studies in knockout mice and humans that the
      cytosolic RIG-I-like receptor MDA5 (IFIH1) has an important role in the host
      defense against C. albicans. Firstly, IFIH1 expression in macrophages is
      specifically induced by invasive C. albicans hyphae, and patients suffering from
      chronic mucocutaneous candidiasis (CMC) express lower levels of MDA5 than healthy
      controls. Secondly, there is a strong association between missense variants in
      the IFIH1 gene (rs1990760 and rs3747517) and susceptibility to systemic Candida
      infections. Thirdly, cells from Mda5 knockout mice and human peripheral blood
      mononuclear cells (PBMCs) with different IFIH1 genotypes display an altered
      cytokine response to C. albicans. These data strongly suggest that MDA5 is
      involved in immune responses to Candida infection. As a receptor for viral RNA,
      MDA5 until now has been linked to antiviral host defense, but these novel studies
      show unexpected effects in antifungal immunity as well. Future studies are
      warranted to explore the potential of MDA5 as a novel target for
      immunotherapeutic strategies. 

PMID- 25579798
TI  - Study on erythrosine-phen-Cd(II) systems by resonance Rayleigh scattering,
      absorption spectra and their analytical applications.
AB  - In pH 7.0-8.0 KH2PO4-Na2HPO4 buffer solution, Cd(II) reacted with 1,10
      phenanthroline to form chelate cation [Cd(phen)3]2+, which further reacted with
      anion of erythrosine to form ternary ion-association complex through
      electrostatic attraction and hydrophobic effect. This process could result in
      remarkable absorption spectra change and produce obvious fading reaction at 528
      nm. Absorbance change (DeltaA) of system was directly proportional to the
      concentration of Cd(II). Hereby, a highly sensitive spectrophotometric method for
      the determination of Cd(II) was established. The molar absorption coefficient was
      2.29*10(5) L mol(-1) cm(-1) and the detection limit of Cd(II) was 26.5 ng mL(-1).
      Furthermore, the resonance Rayleigh scattering (RRS) of this system with two
      peaks located at 371 and 590 nm enhanced significantly, and second-order
      scattering (SOS) and frequence doubling scattering (FDS) of this system changed
      notably at 640 and 350 nm, respectively. Under the optimum conditions, the
      scattering intensities (DeltaIRRS, DeltaIDWO-RRS, DeltaISOS and DeltaIFDS) had
      good linear relationship with the concentration of Cd(II) in certain ranges. The
      detection limits of Cd(II) were 1.27 ng mL(-1), 1.39 ng mL(-1), 4.03 ng mL(-1),
      5.92 ng mL(-1) and 14.7 ng mL(-1) for dual-wavelength overlapping resonance
      Rayleigh scattering (DWO-RRS), RRS (371 nm), RRS (590 nm), SOS and FDS,
      respectively. In addition, the suitable reaction conditions and effects of
      coexisting substances were investigated. The methods had been successfully
      applied to the determination of Cd(II) in environmental water samples. The
      recovery range was between 93.0% and 103.0% and the relative standard deviation
      (RSD) was between 2.5% and 4.3%. The results were in agreement with those
      obtained from atomic absorption spectroscopy.

PMID- 25579799
TI  - Synthesis, spectroscopic, thermal and antimicrobial studies of neodymium(III) and
      samarium(III) complexes derived from tetradentate ligands containing N and S
      donor atoms.
AB  - Trivalent lanthanide complexes of the type [Ln(L)Cl(H2O)2] (where Ln=Nd(III) or
      Sm(III) and LH2=Schiff bases derived by the condensation of 3
      (phenyl/substitutedphenyl)-4-amino-5-mercapto-1,2,4-triazole with
      diacetyl/benzil) have been synthesized by the reactions of anhydrous
      lanthanide(III) chloride with Schiff bases in methanol. The structures of the
      complexes have been proposed on the basis of elemental analysis, electrical
      conductance, magnetic moment, spectroscopic measurements (IR, 1H, 13C NMR and UV
      vis spectra) and X-ray diffraction studies. The spectral data reveal that the
      Schiff base ligands behave as dibasic tetradentate chelating agents having
      coordination sites at two thiol sulfur atoms and two azomethine nitrogen atoms.
      The presence of coordinated water in metal complexes was confirmed by thermal and
      IR data of the complexes. All the Schiff bases and their metal complexes have
      also been screened for their antibacterial activity against Bacillus subtilis,
      Staphylococcus aureus and antifungal activities against Aspergillus niger,
      Curvularia pallescens and Colletotrichum capsici.

PMID- 25579800
TI  - Raman spectroscopic evidence of low temperature stability of D,L-glycolic and L
      (+)-lactic acid crystals.
AB  - Raman and infrared spectra of polycrystalline D,L-glycolic and L-(+) lactic acid
      are presented and assigned both by an ab initio calculation of normal modes of
      free conformers and by self-consistent-charge density-functional-theory
      computational program DFTB+. Temperature dependent Raman spectra from 295 K to 10
      K reveal great stability of crystal lattices, since no soft modes and no band
      splittings that could be attributed to changes of the number of molecules per
      unit cell were observed. A semiempirical calculation with GULP program was used
      to estimate the strength of hydrogen bonds in crystals: in glycolic acid they
      have energies of -0.337 eV/mol, -0.329 eV/mol, -0.262 eV/mol and -0.242 eV/mol,
      while in lactic acid two hydrogen bonds have energies of -0.283 eV/mol and -0.202
      eV/mol.

PMID- 25579802
TI  - Future projections of total hip and knee arthroplasty in the UK: results from the
      UK Clinical Practice Research Datalink.
AB  - OBJECTIVE: To estimate the future rate of primary total hip (THR) or knee (TKR)
      replacement in the UK to 2035 allowing for changes in population demographics and
      obesity. DESIGN: Using age/gender/body mass index (BMI)-specific incidence rates
      from a population-based cohort study of 50,000 THR and 45,609 TKR patients from
      the UK Clinical Practice Research Datalink (CPRD) between 1991 and 2010, we
      projected future numbers of THR and TKR using two models: a static, estimated
      rate from 2010 applied to population growth forecasts to 2035, and a log-linear
      rate extrapolation over the same period. Both scenarios used population forecast
      data from the UK Office for National Statistics (ONS). RESULTS: Assuming rates of
      THR and TKR for 2010, and given projected population changes in age, gender and
      BMI, the number of THRs and TKRs performed in the UK in 2035 is estimated to be,
      respectively: 95,877 and 118,666. By comparison, an exponential extrapolation of
      historical rates using a log-linear model produces much higher estimates of THR
      and TKR counts in 2035 at 439,097 and 1,219,362 respectively. Projected counts
      were higher for women than men. Assuming a changing (rather than fixed) future
      BMI distribution increases TKRs by 2035 but not THRs. CONCLUSIONS: Using
      historical rates and population forecasts we have projected the number of THR/TKR
      operations in the UK up to 2035. This study will inform policymakers requiring
      estimates of future demand for surgery. Incorporating future forecasts for BMI
      into projections of joint replacement may be more relevant for TKR rather than
      THR.

PMID- 25579801
TI  - Reclaiming fertility awareness methods to inform timed intercourse for HIV
      serodiscordant couples attempting to conceive.
AB  - INTRODUCTION: Increased life expectancy of HIV-positive individuals during recent
      years has drawn attention to their quality of life, which includes fulfillment of
      fertility desires. In particular, heterosexual HIV serodiscordant couples
      constitute a special group for whom the balance between desired pregnancy and the
      risk of viral transmission should be carefully considered and optimized. Although
      advanced assisted reproductive technologies are available, such treatments are
      expensive and are often unavailable. Moreover, standard viral load testing and
      antiretroviral therapy may not be accessible due to structural or individual
      barriers. To reduce the risk of HIV transmission, a lower cost alternative is
      timed condomless sex combined with other risk-reduction strategies. However,
      timed condomless sex requires specific knowledge of how to accurately predict the
      fertile window in a menstrual cycle. The aim of this study was to summarize
      inexpensive fertility awareness methods (FAMs) that predict the fertile window
      and may be useful for counselling HIV-positive couples on lower cost options to
      conceive. METHODS: Original English-language research articles were identified by
      a detailed Medline and Embase search in July 2014. Relevant citations in the
      included articles were also retrieved. RESULTS AND DISCUSSION: Calendar method,
      basal body temperature and cervicovaginal mucus secretions are the most
      accessible and sensitive FAMs, although poor specificity precludes their
      independent use in ovulation detection. In contrast, urinary luteinizing hormone
      testing is highly specific but less sensitive, and more expensive. To maximize
      the chance of conception per cycle, the likelihood of natural conception needs to
      be assessed with a basic fertility evaluation of both partners and a combination
      of FAMs should be offered. Adherence to other risk-reduction strategies should
      also be advised, and timely referral to reproductive medicine specialists is
      necessary when sub/infertility is suspected. CONCLUSIONS: FAMs provide effective,
      economical and accessible options for HIV serodiscordant couples to conceive
      while minimizing unnecessary viral exposure. It is important for health care
      providers to initiate conversations about fertility desires in HIV-positive
      couples and to educate identified couples on safer conception strategies.

PMID- 25579803
TI  - A review of the evolution of systemic chemotherapy in the management of
      colorectal cancer.
AB  - Herein we present a historical review of the development of systemic chemotherapy
      for colorectal cancer (CRC) in the metastatic and adjuvant treatment settings. We
      describe the discovery of 5-fluorouracil (5-FU) by Heidelberger and colleagues in
      1957, the potentiation of 5-FU cytotoxicity by the reduced folate leucovorin, and
      the advent of novel cytotoxic agents, including the topoisomerase I inhibitor
      irinotecan, the platinum-containing agent oxaliplatin, and the 5-FU prodrug
      capecitabine. The combination therapies, FOLFOX (5-FU/leucovorin and oxaliplatin)
      and FOLFIRI (5-FU/leucovorin and irinotecan), have become established as
      efficacious cytotoxic regimens for the treatment of metastatic CRC, resulting in
      overall survival times of approximately 2 years. When used as adjuvant therapy,
      FOLFOX also improves survival and is now the gold standard of care in this
      setting. Biological agents have been discovered that enhance the effect of
      cytotoxic therapy, including bevacizumab (a humanized monoclonal antibody that
      targets vascular endothelial growth factor, a central regulator of angiogenesis)
      and cetuximab/panitumumab (monoclonal antibodies directed against the epidermal
      growth factor receptor). Despite the ongoing development of novel antitumor
      agents and therapeutic principles as we enter the era of personalized cancer
      medicine, systemic chemotherapy involving infusional 5-FU/leucovorin continues to
      be the cornerstone of treatment for patients with CRC. 

PMID- 25579804
TI  - Achieving sustained virological response: what's the impact on further hepatitis
      C virus-related disease?
AB  - Continuous hepatic inflammation as a result of chronic infection with the
      hepatitis C virus may lead to the development of fibrosis and eventually
      cirrhosis. At the stage of cirrhosis, patients are at elevated risk of liver
      failure and hepatocellular carcinoma, two complications that shorten their life
      expectancy. Survival may be further impaired by the extra-hepatic manifestations
      of chronic hepatitis C virus infection, such as diabetes mellitus and lymphoma.
      Sustained virological response (SVR) following antiviral therapy has been
      associated with regression of hepatic fibrosis as well as with a reduction in
      portal pressure, both important markers of liver disease severity. Long-term
      follow-up studies indicated that SVR was related not only to a reduced occurrence
      of solid clinical end points, including liver failure and hepatocellular
      carcinoma, but also cardiovascular events and malignant lymphomas. Together,
      these findings may explain the recently observed improved overall survival among
      patients who attained SVR, even in the case of advanced liver disease. 

PMID- 25579806
TI  - Effect of UV-B radiation on the antibody response of fish - implication on high
      altitude fish culture.
AB  - Literally, all living forms are either directly or indirectly dependent upon sun
      for energy. Radiation from sun is differentiated into several components of a
      spectrum based on the wavelength. Ultraviolet (UV) radiation may be one of the
      infamous radiations emitted by the sun. Ozone depletion is another critical
      factor by which UV induced ill-effects are intensified. Though there are numerous
      studies on effects of UV radiation on terrestrial organisms, its effect on
      freshwater and aquaculture ecosystems has been largely neglected. Here, we report
      that enhanced UV irradiation may suppress the primary and secondary antibody
      responses to a soluble protein antigen in fish. Fishes exposed for longer periods
      (80min) were particularly very sensitive to infection, as shown by our
      sensitivity index. 

PMID- 25579805
TI  - Rod and cone contributions to the dark-adapted 15-Hz flicker electroretinogram.
AB  - PURPOSE: To evaluate rod and cone contributions to the dark-adapted 15-Hz flicker
      electroretinogram (ERG) across a broad range of stimulus luminances by comparing
      rod-isolating (ERGR), cone-isolating (ERGC), and non-receptor-specific (ERGR+C)
      responses. METHODS: Dark-adapted, full-field 15-Hz ERGs were obtained from four
      normally sighted subjects (ages 29-36 years) using a four-primary LED-based
      stimulating system. The primaries were either modulated sinusoidally in phase
      (ERGR+C) or were modulated in counter-phase to achieve rod isolation (ERGR) or
      cone isolation (ERGC) by means of triple silent substitution. Measurements were
      made for a broad range of luminances (-2.5 to 1.8 log scot. cd/m(2) in 0.2 log
      unit steps). Fourier analysis was used to obtain the amplitude and phase of the
      fundamental response component at each stimulus luminance. RESULTS: Stimulus
      luminance had different effects on response amplitudes and phases under the three
      paradigms. Specifically, ERGC amplitude and phase increased monotonically as
      luminance increased. The effects on ERGR+C and ERGR were complex: ERGR+C and ERGR
      amplitude was small and the phase decreased for low luminances, whereas amplitude
      and phase increased sharply at moderate luminances. For high luminances, ERGR+C
      amplitude and phase increased, whereas ERGR amplitude decreased and phase was
      approximately constant. CONCLUSIONS: At low luminances, the ERGR+C and ERGR
      functions can be attributed to interactions between two rod pathways. At high
      luminances, the functions can be accounted for by interactions between rod and
      cone pathways (ERGR+C) or rod insensitivity (ERGR). The ERGR paradigm minimizes
      cone intrusion, permitting assessment of rod function over a large range of
      luminance levels.

PMID- 25579807
TI  - Contribution of UVA irradiance to the erythema and photoaging effects in solar
      and sunbed exposures.
AB  - Even though UVA irradiance had not been considered detrimental to human skin for
      years, nowadays it is recognized for its role in photoaging and other biological
      responses. The ratio UVA/UVB is about 17 at a solar zenith angle (SZA) of 20
      degrees  and it is almost constant up to 60 degrees  when it rapidly increases
      since the UVB wavelengths (280-320nm) are more attenuated than the UVA waveband
      (320-400nm). For a constant SZA, the ratio increases with the ozone content. The
      UVA component of the solar erythemal irradiance ranges from 20% at 20 degrees  to
      30% at 60 degrees , whereas it varies from 50% to 80% in the two different types
      of measured sunbeds. Moreover, the different spectral distribution of the lamps
      used for artificial tanning leads frequently to high UVA doses. The biological
      responses related to skin photoaging (skin sagging and elastosis) could be around
      fourfold the equivalent solar irradiance at midday in summer midlatitudes and
      they can be important in unprotected UVA exposures to sunbeds. The UVA dose
      accumulated during the time required in reaching 1 minimum erythemal dose (MED)
      increases with the SZA since the exposure durations are longer. Indeed, seasonal
      differences in the mean UVA dose are observed due to variations in the ozone
      content that results in longer exposure times without erythema. Although an
      artificial tanning session is usually shorter than one hour, the UVA dose from
      sunbeds during the time for 1 MED for skin type II (250Jm(-2)) can be 2-4 times
      larger than the solar dose, depending on the lamp spectral emission. 

PMID- 25579808
TI  - In vitro human cell responses to a low-dose photodynamic treatment vs. mild H2O2
      exposure.
AB  - Photodynamic treatments allow control of the amount of reactive oxygen species
      (ROS) produced through the photosensitizer concentration and the light dose
      delivered to the target. In this way low ROS doses can be achieved in situ to
      study cell responses related to redox regulation. In this study a comparison has
      been made between different cell responses to a low-dose photodynamic treatment
      and both low and relatively high concentrations of H2O2 in human immortalized
      keratinocytes (HaCaT). The obtained results show that the photodynamic treatment
      induces a stimulating cell response roughly equivalent to that produced by
      exposing cells to 10(-5)M H2O2. Higher H2O2 concentrations gave rise to
      concentration-dependent deleterious effects on the cell cultures. Of importance
      is that the photodynamic treatment did not produce genotoxic damage, as measured
      by micronuclei frequency, while cultures exposed to 10(-5)M H2O2 displayed a
      significant increase in the amount of cells with micronuclei. In summary, the low
      dose photodynamic treatment promotes cell proliferation but does not incur in the
      excessive clastogenic lesions observed after H2O2 exposure. It is therefore
      proposed as a promising alternative to direct H2O2 exposure in the study of cell
      redox signalling. 

PMID- 25579809
TI  - Negative predictive value of drain amylase concentration for development of
      pancreatic fistula after pancreaticoduodenectomy.
AB  - BACKGROUND: Post-operative pancreatic fistula (POPF) is the major source of
      morbidity following pancreaticoduodenectomy. A predictive indicator would be
      highly advantageous. One potential marker is drain amylase concentration (DAC).
      However, its predictive value has not been fully established. METHODS: 405
      patients undergoing pancreaticoduodenectomy at our centre over a 10 year period
      were reviewed to determine the value of DAC as a predictive indicator for the
      development of POPF. RESULTS: POPF developed in 58 patients (14%). These patients
      suffered greater morbidity. Overall 30-day mortality was 1.5%. Male gender (OR:
      5.1; p = 0.0082) and age > 70 (OR 2; p = 0.0372) were independent risk factors
      for POPF, whilst Type 2 diabetes (OR: 0.2321; p = 0.0090) and pancreatic ductal
      adenocarcinoma (OR: 0.3721; p = 0.0039) decreased POPF risk. The DACs post
      operatively were significantly higher in those developing POPF, but with
      significant overlap. ROC curves revealed optimal threshold values for
      differentiating POPF and non-POPF patients. A DAC degrees < degrees 1400 U/ml on
      day 1 and <768 U/ml on day 2, although having a poor positive predictive value
      (32-44%), had a very strong negative predictive value (97-99%). CONCLUSION: Our
      data suggest that post-operative DAC below the determined optimal threshold
      values on day 1 and 2 following pancreaticoduodenectomy carries high negative
      predictive value for POPF development and identifies patients in whom early drain
      removal, and enhanced recovery may be considered, with simultaneous assessment of
      operative and clinical factors.

PMID- 25579814
TI  - Structural plasticity of methyllysine recognition by the tandem tudor domain of
      53BP1.
AB  - p53 is dynamically regulated through various posttranslational modifications
      (PTMs), which differentially modulate its function and stability. The
      dimethylated marks p53K370me2 and p53K382me2 are associated with p53 activation
      or stabilization and both are recognized by the tandem Tudor domain (TTD) of
      53BP1, a p53 cofactor. Here we detail the molecular mechanisms for the
      recognition of p53K370me2 and p53K382me2 by 53BP1. The solution structures of TTD
      in complex with the p53K370me2 and p53K382me2 peptides show a remarkable
      plasticity of 53BP1 in accommodating these diverse dimethyllysine-containing
      sequences. We demonstrate that dimeric TTDs are capable of interacting with the
      two PTMs on a single p53K370me2K382me2 peptide, greatly strengthening the 53BP1
      p53 interaction. Analysis of binding affinities of TTD toward methylated p53 and
      histones reveals strong preference of 53BP1 for p53K382me2, H4K20me2, and
      H3K36me2 and suggests a possible role of multivalent contacts of 53BP1 in p53
      targeting to and accumulation at the sites of DNA damage.

PMID- 25579816
TI  - Increased reliability of nuclear magnetic resonance protein structures by
      consensus structure bundles.
AB  - Nuclear magnetic resonance (NMR) structures are represented by bundles of
      conformers calculated from different randomized initial structures using
      identical experimental input data. The spread among these conformers indicates
      the precision of the atomic coordinates. However, there is as yet no reliable
      measure of structural accuracy, i.e., how close NMR conformers are to the "true"
      structure. Instead, the precision of structure bundles is widely (mis)interpreted
      as a measure of structural quality. Attempts to increase precision often
      overestimate accuracy by tight bundles of high precision but much lower accuracy.
      To overcome this problem, we introduce a protocol for NMR structure determination
      with the software package CYANA, which produces, like the traditional method,
      bundles of conformers in agreement with a common set of conformational restraints
      but with a realistic precision that is, throughout a variety of proteins and NMR
      data sets, a much better estimate of structural accuracy than the precision of
      conventional structure bundles. 

PMID- 25579815
TI  - The origin of CDR H3 structural diversity.
AB  - Antibody complementarity determining region (CDR) H3 loops are critical for
      adaptive immunological functions. Although the other five CDR loops adopt
      predictable canonical structures, H3 conformations have proven unclassifiable,
      other than an unusual C-terminal "kink" present in most antibodies. To determine
      why the majority of H3 loops are kinked and to learn whether non-antibody
      proteins have loop structures similar to those of H3, we searched a set of 15,679
      high-quality non-antibody structures for regions geometrically similar to the
      residues immediately surrounding the loop. By incorporating the kink into our
      search, we identified 1,030 H3-like loops from 632 protein families. Some protein
      families, including PDZ domains, appear to use the identified region for
      recognition and binding. Our results suggest that the kink is conserved in the
      immunoglobulin heavy chain fold because it disrupts the beta-strand pairing at
      the base of the loop. Thus, the kink is a critical driver of the observed
      structural diversity in CDR H3. 

PMID- 25579817
TI  - The LisH motif of muskelin is crucial for oligomerization and governs
      intracellular localization.
AB  - Neurons regulate the number of surface receptors by balancing the transport to
      and from the plasma membrane to adjust their signaling properties. The protein
      muskelin was recently identified as a key factor guiding the transport of alpha1
      subunit-containing GABAA receptors. Here we present the crystal structure of
      muskelin, comprising its N-terminal discoidin domain and Lis1-homology (LisH)
      motif. The molecule crystallized as a dimer with the LisH motif exclusively
      mediating oligomerization. Our subsequent biochemical analyses confirmed that the
      LisH motif acts as a dimerization element in muskelin. Together with an
      intermolecular head-to-tail interaction, the LisH-dependent dimerization is
      required to assemble a muskelin tetramer. Intriguingly, our cellular studies
      revealed that the loss of this dimerization results in a complete redistribution
      of muskelin from the cytoplasm to the nucleus and impairs muskelin's function in
      GABAA receptor transport. These studies demonstrate that the LisH-dependent
      dimerization is a crucial factor for muskelin function.

PMID- 25579818
TI  - Structural insights into the initiating complex of the lectin pathway of
      complement activation.
AB  - The proteolytic cascade of the complement system is initiated when pattern
      recognition molecules (PRMs) bind to ligands, resulting in the activation of
      associated proteases. In the lectin pathway of complement, the complex of mannan
      binding lectin (MBL) and MBL-associated serine protease-1 (MASP-1) initiates the
      pathway by activating a second protease, MASP-2. Here we present a structural
      study of a PRM/MASP complex and derive the overall architecture of the 450 kDa
      MBL/MASP-1 complex using small-angle X-ray scattering and electron microscopy.
      The serine protease (SP) domains from the zymogen MASP-1 dimer protrude from the
      cone-like MBL tetramer and are separated by at least 20 nm. This suggests that
      intracomplex activation within a single MASP-1 dimer is unlikely and instead
      supports intercomplex activation, whereby the MASP SP domains are accessible to
      nearby PRM-bound MASPs. This activation mechanism differs fundamentally from the
      intracomplex initiation models previously proposed for both the lectin and the
      classical pathway.

PMID- 25579819
TI  - Genome-wide copy number scan identifies IRF6 involvement in Van der Woude
      syndrome in an Indian family.
AB  - Summary Van der Woude syndrome (VWS) is an autosomal dominant developmental
      malformation presenting with bilateral lower lip pits related to cleft lip, cleft
      palate and other malformations. We performed a whole-genome copy number
      variations (CNVs) scan in an Indian family with members suffering from VWS using
      2.6 million combined SNP and CNV markers. We found CNVs affecting IRF6, a known
      candidate gene for VWS, in all three cases, while none of the non-VWS members
      showed any CNVs in the IRF6 region. The duplications and deletions of the
      chromosomal critical region in 1q32-q41 confirm the involvement of CNVs in IRF6
      in South Indian VWS patients. Molecular network analysis of these and other cleft
      lip/palate related module genes suggests that they are associated with cytokine
      mediated signalling pathways and response to interferon-gamma mediated signalling
      pathways. This is a maiden study indicating the involvement of CNVs in IRF6 in
      causing VWS in the Indian population. 

PMID- 25579820
TI  - Critical reappraisal of intravenous metoclopramide in migraine attack: a
      systematic review and meta-analysis.
AB  - Migraine is one of the most common causes of headache presentations to emergency
      departments (EDs). Patients with migraine attack need rapid pain relief rather
      than diagnostic modalities. Metoclopramide, a dopamine antagonist with a primary
      use of antiemetic, has been used commonly in ceasing migraine attack. An earlier
      meta-analysis favors metoclopramide over placebo but includes studies with
      significant methodological errors and heterogeneity. The present article aimed to
      review the literature to reveal studies comparing metoclopramide to either
      placebo or active comparators. A literature search including PubMed, Cochrane
      Database, and Google Scholar was performed by using the evidence-based process
      for determining the study quality. Although the studies comparing parenteral
      metoclopramide to placebo in ceasing migraine headache favor metoclopramide to
      placebo and lower rates of rescue drug need, however, they lack high
      methodological quality even to perform a meta-analysis. Meanwhile, the effect of
      metoclopramide in ceasing migraine headache is also comparable to active
      comparators. It seems reasonable to use metoclopramide in migraine attacks in EDs
      according to the current literature. However, further studies with high
      methodological quality are needed to reveal whether and how much metoclopramide
      is superior to placebo. 

PMID- 25579824
TI  - Two-level lumbar total disc replacement: functional outcomes and segmental motion
      after 4 years.
AB  - INTRODUCTION: Lumbar total disc replacement is an effective treatment for single
      level discogenic lower back pain. But the replacement of two disc levels is
      controversial. HYPOTHESIS: Two-level total disc replacement will improve function
      while preserving spinal motion. MATERIAL AND METHODS: A continuous series of 108
      patients (51 women, 57 men) surgically treated over two levels with the ProDisc-L
      implant (Synthes Spine) was evaluated retrospectively with an average follow-up
      of 4 years. Ninety-three of these patients were operated for L4/L5 and L5/S1
      degenerative disc disease, while 15 were operated for L3/L4 and L4/L5 disease.
      The procedure was carried out through the left retroperitoneal approach in 65
      patients, the right retroperitoneal approach in 42 patients and both approaches
      in 1 patient. The Oswestry score, lumbar VAS and radicular VAS were used to
      evaluate function. The motion of the prosthetic disc segments was evaluated using
      Cobb's method. Data were collected prospectively in the context of regular
      patient monitoring. A retrospective analysis was carried out by an independent
      examiner. RESULTS: The procedure led to a statistically significant improvement
      in the functional scores. The motion of the upper disc segment was 9 degrees  (0
      degrees -19 degrees ) in flexion/extension and 5.5 degrees  (2 degrees -12
      degrees ) in lateral bending. It was 6.2 degrees  (0 degrees -14 degrees ) and
      1.9 degrees  (0 degrees -7 degrees ) at the lower disc segment. The range of
      motion was similar in L3/L4 and L4/L5, but was less in L5/S1. Lack of mobility
      was not correlated with alterations in the functional outcome. The complication
      rate was 18%. DISCUSSION: Two-level lumbar disc replacement improves spinal
      function while preserving its mobility. But this procedure is fraught with risks
      and must be carried out by a highly-experienced team. A longer follow-up is
      needed to evaluate the sustainability of the results and to detect any adjacent
      segment disease. The French National Authority for Health (HAS) has recommended
      against two-level lumbar disc replacement, so it no longer can be performed in
      France.

PMID- 25579825
TI  - Bone cysts: unicameral and aneurysmal bone cyst.
AB  - Simple and aneurysmal bone cysts are benign lytic bone lesions, usually
      encountered in children and adolescents. Simple bone cyst is a cystic, fluid
      filled lesion, which may be unicameral (UBC) or partially separated. UBC can
      involve all bones, but usually the long bone metaphysis and otherwise primarily
      the proximal humerus and proximal femur. The classic aneurysmal bone cyst (ABC)
      is an expansive and hemorrhagic tumor, usually showing characteristic
      translocation. About 30% of ABCs are secondary, without translocation; they occur
      in reaction to another, usually benign, bone lesion. ABCs are metaphyseal,
      excentric, bulging, fluid-filled and multicameral, and may develop in all bones
      of the skeleton. On MRI, the fluid level is evocative. It is mandatory to
      distinguish ABC from UBC, as prognosis and treatment are different. UBCs resolve
      spontaneously between adolescence and adulthood; the main concern is the risk of
      pathologic fracture. Treatment in non-threatening forms consists in intracystic
      injection of methylprednisolone. When there is a risk of fracture, especially of
      the femoral neck, surgery with curettage, filling with bone substitute or graft
      and osteosynthesis may be required. ABCs are potentially more aggressive, with a
      risk of bone destruction. Diagnosis must systematically be confirmed by biopsy,
      identifying soft-tissue parts, as telangiectatic sarcoma can mimic ABC. Intra
      lesional sclerotherapy with alcohol is an effective treatment. In spinal ABC and
      in aggressive lesions with a risk of fracture, surgical treatment should be
      preferred, possibly after preoperative embolization. The risk of malignant
      transformation is very low, except in case of radiation therapy. 

PMID- 25579826
TI  - The keyhole technique for arthroscopic tenodesis of the long head of the biceps
      tendon. In vivo prospective study with a radio-opaque marker.
AB  - INTRODUCTION: In some clinical situations such as when the Long Head of the
      Biceps (LHB) is unstable or with an "hourglass biceps", treatment is required.
      Tenodesis is an alternative to tenotomy to prevent the Popeye sign. Although
      sutures, anchors or interference screws may be used, they all have complications
      and drawbacks. Moreover, the number of failures is underestimated because it only
      considers the visible deformities of the arm. MRI provides more accurate
      assessment, but is more expensive. We hypothesized that Froimson's "keyhole
      technique" which has been described in open surgery could be performed
      arthroscopically with similar clinical outcomes to conventional techniques and
      without the complications or drawbacks. We also propose an objective and less
      expensive assessment of treatment failure. MATERIALS AND METHODS: This 12-month
      prospective study was performed by a single surgeon. All patients requiring LHB
      tenodesis underwent arthroscopic "keyhole technique" surgery performed at the
      upper edge of the Pectoralis major in the bicipital groove. The LHB was
      externalised, pulled back on itself and the intra-articular portion was resected.
      A metal marker was placed in the tendon. The latter was introduced into the
      keyhole and hangs spontaneously. The follow-up evaluation was performed during
      the third month with a clinical examination and a plain X-ray. Distal migration
      of the metal marker was the sign of the failure of tenodesis. RESULTS: Between
      January 1st and December 31st, 2013, 123 patients were included. There were 87
      men (70.7%) and 36 women (29.3%) and mean age was 52.2 (27-71). Eighty-eight
      patients underwent arthroscopic rotator cuff repair. Twenty-three patients
      (18.5%) had tenodesis failure shown by distal migration of the metal marker on
      plain X-rays. There were 21 men and 2 women. Only 13 had a visible Popeye sign
      and 1 was severe. None of the patients felt any discomfort, fatigue or painful
      cramping. There was no difference in flexion and supination strength from the
      healthy side. No complications were noted. DISCUSSION AND CONCLUSION: We confirm
      the hypothesis that this arthroscopic technique is feasible and reproducible with
      clinical outcomes similar to conventional techniques but without the
      complications. The metal marker implanted in the LHB confirms the exact number of
      failures, which is a significant element in this study. LEVEL OF EVIDENCE: IV.

PMID- 25579827
TI  - Intraoperative determination of lumbar prosthesis endplate lordotic angulation to
      improve motion.
AB  - The aim of total disc replacement (TDR) is to restore and maintain closer-to
      physiology motion. Therefore, the factors that influence postoperative
      intervertebral motion have to be controlled. Factors such as disc height (DH),
      postoperative segmental lordosis (SL), implant design and positioning are still
      recognized to be influent. Otherwise, range of motion (ROM) distribution, between
      flexion and extension, appear to be influenced by obtaining parallel bearing
      surfaces, which depends on prosthesis endplate lordotic angulation. To assess in
      vivo the correlation between an intraoperative parameter (intraoperative
      segmental lordosis: ISL) and a postoperative parameter (postoperative segmental
      lordosis: PSL). To determine the advantage of ISL measurement on the improvement
      of the prosthetic endplate lordotic angulation choice. Radiological comparison
      between intraoperative and postoperative segmental parameters. Fifty-seven
      patients who received a TDR at one level, L4-L5 or L5-S1, with different
      prosthetic endplate lordotic angulations (0 degrees , 5 degrees , and 10 degrees
      ). Twenty-one consecutive patients underwent intraoperative measurement (ISL) on
      a lateral view, with a spacer at the mid-vertebral bony endplates (Group 1). ISL
      was correlated using a linear correlation test with PSL. Group 1 postoperative
      prosthesis endplate lordosis (PEL: angle between the bearing surfaces) were
      compared to those of 46 patients without intraoperative measurement (Group 2).
      The mean ISL and PSL angles were 12.2 degrees  (7-21 degrees ) and 13.9 degrees 
      (8-23 degrees ), respectively. We observed a strong linear correlation between
      ISL and PSL (r=0.78, P <0.006). In Group 1, PEL varied between -1 degrees  and 11
      degrees , and between -3.7 degrees  and 17.8 degrees  in Group 2. For 80% of the
      patients in Group 1, the PEL was less than 5 degrees , versus 33% of the patients
      in Group 2. Only prostheses with PEL less than 5 degrees  had a preserved
      extension curve in ROM distribution (+3 degrees ). Intraoperative measurement of
      ISL has emerged as a key factor in predicting PSL in TDR. The percentage of
      parallel bearing surfaces was increased by a prosthesis endplate lordotic
      angulation choice guided by ISL measurement. This study confirmed the advantage
      of choosing the adequate lordotic angulation of the prosthesis endplate to
      restore a physiological motion distribution between flexion and extension.

PMID- 25579828
TI  - Non-tuberculous mycobacterial infections of the hand.
AB  - Non-tuberculous mycobacterial infections of the hand are difficult to treat and
      require a long time before remission. But how long should we wait to see an
      improvement? To answer this question, the published scientific literature was
      reviewed in English, French and German. Tuberculosis, arthritis and osteomyelitis
      cases were excluded. A total of 241 non-tuberculous mycobacterial hand infections
      in 38 scientific publications were retrieved. Most were case reports or series.
      The median age of the patients was 58years and one third was female. Patients
      were immunocompromised in 17 episodes. The most common species were Mycobacterium
      marinum in 198 episodes (82%), followed by M. chelonae in 13 cases (5%). There
      were no cases of mixed infection. Most infections were aquatic in origin and
      community-acquired, and were treated with a combination of surgical debridement
      and long-duration systemic combination antibiotic therapy (14 different regimens;
      no local antibiotics) for a median duration of 6months. The median number of
      surgical procedures was 2.5 (range 1-5). Clinical success was not immediate: a
      median period of 3months (range 2-6) was necessary before the first signs of
      improvement were observed. The majority (173 cases; 76%) remained entirely cured
      after a median follow-up time of 1.7years (range, 1-6). Only two microbiological
      recurrences occurred (1%). However, 49 patients (21%) had long-term sequelae such
      as pain, stiffness and swelling. The approach of long-duration antibiotic
      treatment in combination with repeated surgery for mycobacterial soft tissue
      infections of the hand leads to few recurrences. However, clinical success is not
      immediate and may take up to 3months. TYPE OF STUDY: Therapeutic study:
      systematic review of level III studies. LEVEL OF EVIDENCE: III.

PMID- 25579829
TI  - Retrograde percutaneous screw fixation for scaphoid type II non-union in
      Schernberg zones 2 to 4: a series of 38 cases.
AB  - Regardless of the treatment used, 25 to 45% of scaphoid fractures do not heal.
      Open surgery compromises vascularization and destabilizes ligament attachments.
      The aim of this retrospective study was to assess the value of retrograde
      percutaneous screw fixation of Alnot stage IIA and IIB scaphoid non-union in
      Schernberg zones 2 to 4. This series included 38 patients with a mean age of 31
      years. Based on the Alnot classification, there were 16 stage IIA non-unions (12
      in zone 3 and 4 in zone 2 according to the Schernberg classification) and 22
      stage IIB non-unions (9 in zone 3 and 13 in zone 2). The time elapsed between the
      initial trauma and the surgical treatment was 10 months on average. Percutaneous
      retrograde fixation was performed with a cannulated 2.7mm compression screw. At
      25 months follow-up, 31 of the non-union cases had healed (81.6%), of which 14
      were stage IIA (87.5%) and 17 were stage IIB (77.3%), after an average 6.3
      months. Average pain was 1.6. The average Quick DASH was 17.3/100. Compared to
      the opposite side, the average range of motion was 84.8% in flexion, 84.7% in
      extension, 98.9% in pronation, 96.5% in supination, 96.8% in ulnar deviation and
      86.4% in radial deviation. The grip strength was 80.4% of the contralateral side.
      Seven patients did not heal after screw fixation; four of them healed after
      additional electromagnetic stimulation and three after addition of a vascularized
      bone graft. Based on this study's results, stage IIA non-unions can heal with
      simple retrograde percutaneous screw fixation. The same procedure could be enough
      for stage IIB non-union cases, however we recommend adding a cancellous bone
      graft by arthroscopy. Open surgery procedures are preferred when percutaneous
      procedures have failed.

PMID- 25579833
TI  - School-based suicide prevention programmes: the SEYLE cluster-randomised,
      controlled trial.
AB  - BACKGROUND: Suicidal behaviours in adolescents are a major public health problem
      and evidence-based prevention programmes are greatly needed. We aimed to
      investigate the efficacy of school-based preventive interventions of suicidal
      behaviours. METHODS: The Saving and Empowering Young Lives in Europe (SEYLE)
      study is a multicentre, cluster-randomised controlled trial. The SEYLE sample
      consisted of 11,110 adolescent pupils, median age 15 years (IQR 14-15), recruited
      from 168 schools in ten European Union countries. We randomly assigned the
      schools to one of three interventions or a control group. The interventions were:
      (1) Question, Persuade, and Refer (QPR), a gatekeeper training module targeting
      teachers and other school personnel, (2) the Youth Aware of Mental Health
      Programme (YAM) targeting pupils, and (3) screening by professionals (ProfScreen)
      with referral of at-risk pupils. Each school was randomly assigned by random
      number generator to participate in one intervention (or control) group only and
      was unaware of the interventions undertaken in the other three trial groups. The
      primary outcome measure was the number of suicide attempt(s) made by 3 month and
      12 month follow-up. Analysis included all pupils with data available at each
      timepoint, excluding those who had ever attempted suicide or who had shown severe
      suicidal ideation during the 2 weeks before baseline. This study is registered
      with the German Clinical Trials Registry, number DRKS00000214. FINDINGS: Between
      Nov 1, 2009, and Dec 14, 2010, 168 schools (11,110 pupils) were randomly assigned
      to interventions (40 schools [2692 pupils] to QPR, 45 [2721] YAM, 43 [2764]
      ProfScreen, and 40 [2933] control). No significant differences between
      intervention groups and the control group were recorded at the 3 month follow-up.
      At the 12 month follow-up, YAM was associated with a significant reduction of
      incident suicide attempts (odds ratios [OR] 0.45, 95% CI 0.24-0.85; p=0.014) and
      severe suicidal ideation (0.50, 0.27-0.92; p=0.025), compared with the control
      group. 14 pupils (0.70%) reported incident suicide attempts at the 12 month
      follow-up in the YAM versus 34 (1.51%) in the control group, and 15 pupils
      (0.75%) reported incident severe suicidal ideation in the YAM group versus 31
      (1.37%) in the control group. No participants completed suicide during the study
      period. INTERPRETATION: YAM was effective in reducing the number of suicide
      attempts and severe suicidal ideation in school-based adolescents. These findings
      underline the benefit of this universal suicide preventive intervention in
      schools. FUNDING: Coordination Theme 1 (Health) of the European Union Seventh
      Framework Programme.

PMID- 25579835
TI  - Effectiveness of school-based suicide prevention programmes.

PMID- 25579836
TI  - The 2013 Elliott Youth Development Lecture.

PMID- 25579837
TI  - Antiepileptic C21 steroids from the roots of Cynanchum otophyllum.
AB  - In order to discover more natural products possessing potentially antiepileptic
      activities, three C21 steroids, including a new one, characterized as caudatin-3
      O-beta-D-cymaropyranosyl-(1 -> 4)-beta-D-cymaropyranosyl-(1 -> 4)-beta-D
      cymaropyranoside (1), and two known analogs, otophylloside B (2) and caudatin-3-O
      beta-D-oleandropyranosyl-(1 -> 4)-beta-D-oleandropyranosyl-(1 -> 4)-beta-D
      cymaropyranosyl-(1 -> 4)-beta-D-cymaropyranoside (3), were isolated from the
      chloroform extract of the roots of Cynanchum otophyllum and evaluated for their
      antiepileptic activities by pentylenetrazole (PTZ)-induced zebrafish larval
      locomotor assay. The results showed that all of them had marked activities of
      suppressing PTZ-induced seizure behaviors in larval zebrafish at the dose of 10
      MUg/ml.

PMID- 25579841
TI  - Biomarkers of Alzheimer's disease and mild cognitive impairment: a current
      perspective.
AB  - A growing body of evidence supports the application of the neurochemical dementia
      diagnostics (NDD) biomarkers for the diagnosis of dementing conditions.
      Biomarkers of Alzheimer's disease (AD) were recently classified as these
      reflecting amyloid beta pathology (decreased CSF concentrations of Abeta42 and/or
      positive Abeta PET scan) and these reflecting neurodegeneration (increased CSF
      Tau concentrations, decreased uptake of FDG on FDG-PET, and cerebral atrophy on
      structural MRI). Particularly important seems the role of the biomarkers in the
      early diagnosis of AD, as the first pathophysiologic events observable in the CSF
      and amyloid beta-PET occur years and perhaps decades before the onset of the
      earliest clinical symptoms. Therefore, the NDD tools enable the diagnosis of AD
      already in the early preclinical stage. This review summarizes pathophysiology
      underlying the CSF biomarkers, following a discussion of their role in the
      current guidelines for the diagnostic procedures. 

PMID- 25579834
TI  - Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of
      individual data from 174,000 participants in 27 randomised trials.
AB  - BACKGROUND: Whether statin therapy is as effective in women as in men is debated,
      especially for primary prevention. We undertook a meta-analysis of statin trials
      in the Cholesterol Treatment Trialists' (CTT) Collaboration database to compare
      the effects of statin therapy between women and men. METHODS: We performed meta
      analyses on data from 22 trials of statin therapy versus control (n=134,537) and
      five trials of more-intensive versus less-intensive statin therapy (n=39,612).
      Effects on major vascular events, major coronary events, stroke, coronary
      revascularisation and mortality were weighted per 1.0 mmol/L reduction in LDL
      cholesterol and effects in men and women compared with a Cox model that adjusted
      for non-sex differences. For subgroup analyses, we used 99% CIs to make allowance
      for the multiplicity of comparisons. FINDINGS: 46,675 (27%) of 174,149 randomly
      assigned participants were women. Allocation to a statin had similar absolute
      effects on 1 year lipid concentrations in both men and women (LDL cholesterol
      reduced by about 1.1 mmol/L in statin vs control trials and roughly 0.5 mmol/L
      for more-intensive vs less-intensive therapy). Women were generally at lower
      cardiovascular risk than were men in these trials. The proportional reductions
      per 1.0 mmol/L reduction in LDL cholesterol in major vascular events were similar
      overall for women (rate ratio [RR] 0.84, 99% CI 0.78-0.91) and men (RR 0.78, 99%
      CI 0.75-0.81, adjusted p value for heterogeneity by sex=0.33) and also for those
      women and men at less than 10% predicted 5 year absolute cardiovascular risk
      (adjusted heterogeneity p=0.11). Likewise, the proportional reductions in major
      coronary events, coronary revascularisation, and stroke did not differ
      significantly by sex. No adverse effect on rates of cancer incidence or non
      cardiovascular mortality was noted for either sex. These net benefits translated
      into all-cause mortality reductions with statin therapy for both women (RR 0.91,
      99% CI 0.84-0.99) and men (RR 0.90, 99% CI 0.86-0.95; adjusted heterogeneity
      p=0.43). INTERPRETATION: In men and women at an equivalent risk of cardiovascular
      disease, statin therapy is of similar effectiveness for the prevention of major
      vascular events. FUNDING: UK Medical Research Council, British Heart Foundation,
      Australian National Health and Medical Research Council, European Community
      Biomed Program.

PMID- 25579842
TI  - RSK1 activation promotes invasion in nodular melanoma.
AB  - The two major melanoma histologic subtypes, superficial spreading and nodular
      melanomas, differ in their speed of dermal invasion but converge biologically
      once they invade and metastasize. Herein, we tested the hypothesis that distinct
      molecular alterations arising in primary melanoma cells might persist as these
      tumors progress to invasion and metastasis. Ribosomal protein S6 kinase, 90 kDa,
      polypeptide 1 (RSK1; official name RPS6KA1) was significantly hyperactivated in
      human melanoma lines and metastatic tissues derived from nodular compared with
      superficial spreading melanoma. RSK1 was constitutively phosphorylated at Ser-380
      in nodular but not superficial spreading melanoma and did not directly correlate
      with BRAF or MEK activation. Nodular melanoma cells were more sensitive to RSK1
      inhibition using siRNA and the pharmacological inhibitor BI-D1870 compared with
      superficial spreading cells. Gene expression microarray analyses revealed that
      RSK1 orchestrated a program of gene expression that promoted cell motility and
      invasion. Differential overexpression of the prometastatic matrix
      metalloproteinase 8 and tissue inhibitor of metalloproteinases 1 in metastatic
      nodular compared with metastatic superficial spreading melanoma was observed.
      Finally, using an in vivo zebrafish model, constitutive RSK1 activation increased
      melanoma invasion. Together, these data reveal a novel role for activated RSK1 in
      the progression of nodular melanoma and suggest that melanoma originating from
      different histologic subtypes may be biologically distinct and that these
      differences are maintained as the tumors invade and metastasize. 

PMID- 25579845
TI  - A unique class of neutral cyclometalated platinum(II) complexes with pi-bonded
      benzenedithiolate: synthesis, molecular structures and tuning of luminescence
      properties.
AB  - A unique class of neutral cyclometalated platinum(ii) complexes with pi-bonded
      benzenedithiolate are reported including two X-ray molecular structures. To the
      best of our knowledge these are the first structures to be reported for
      cyclometalated platinum complexes with a benzenedithiolate ligand. All of the
      complexes are luminescent in fluid solution at room temperature and in frozen
      solvent glasses at 77 K and their emission properties can be tuned through ligand
      variation. 

PMID- 25579843
TI  - Inhibition of sphingosine kinase prevents lipopolysaccharide-induced preterm
      birth and suppresses proinflammatory responses in a murine model.
AB  - Premature delivery occurs in 12% of all births, and accounts for nearly half of
      long-term neurological morbidity, and 60% to 80% of perinatal mortality. Despite
      advances in obstetrics and neonatology, the rate of premature delivery has
      increased approximately 12% since 1990. The single most common cause of
      spontaneous preterm birth is infection. Several lines of evidence have
      demonstrated the role of endothelin-1 as both a constrictor of uterine myometrial
      smooth muscle and a proinflammatory mediator. Endothelin-1 activates the
      phospholipase C pathway, leading to activation of protein kinase C and, in turn,
      sphingosine kinase (SphK). The inhibition of SphK has been recently shown to
      control the proinflammatory response associated with sepsis. We show herein, for
      the first time, that SphK inhibition prevents inflammation-associated preterm
      birth in a murine model. Rescue of pups from premature abortion with an SphK
      inhibitor occurs by suppression of the proinflammatory cytokines tumor necrosis
      factor alpha, Il-1beta, and Il-6 and attenuation of polymorphonuclear
      inflammatory cells into the placental labyrinth. Moreover, we postulate that
      inhibition of SphK leads to suppression of endothelin-converting enzyme-1
      expression, indicating the presence of an endothelin-converting enzyme
      1/endothelin 1-SphK positive feedback loop. This work introduces a novel approach
      for the control of infection-triggered preterm labor, a condition for which there
      is no effective treatment. 

PMID- 25579844
TI  - Lipolysis of visceral adipocyte triglyceride by pancreatic lipases converts mild
      acute pancreatitis to severe pancreatitis independent of necrosis and
      inflammation.
AB  - Visceral fat necrosis has been associated with severe acute pancreatitis (SAP)
      for over 100 years; however, its pathogenesis and role in SAP outcomes are poorly
      understood. Based on recent work suggesting that pancreatic fat lipolysis plays
      an important role in SAP, we evaluated the role of pancreatic lipases in SAP
      associated visceral fat necrosis, the inflammatory response, local injury, and
      outcomes of acute pancreatitis (AP). For this, cerulein pancreatitis was induced
      in lean and obese mice, alone or with the lipase inhibitor orlistat and
      parameters of AP induction (serum amylase and lipase), fat necrosis, pancreatic
      necrosis, and multisystem organ failure, and inflammatory response were assessed.
      Pancreatic lipases were measured in fat necrosis and were overexpressed in 3T3-L1
      cells. We noted obesity to convert mild cerulein AP to SAP with greater
      cytokines, unsaturated fatty acids (UFAs), and multisystem organ failure, and
      100% mortality without affecting AP induction or pancreatic necrosis. Increased
      pancreatic lipase amounts and activity were noted in the extensive visceral fat
      necrosis of dying obese mice. Lipase inhibition reduced fat necrosis, UFAs, organ
      failure, and mortality but not the parameters of AP induction. Pancreatic lipase
      expression increased lipolysis in 3T3-L1 cells. We conclude that UFAs generated
      via lipolysis of visceral fat by pancreatic lipases convert mild AP to SAP
      independent of pancreatic necrosis and the inflammatory response. 

PMID- 25579848
TI  - Investigation on the effect of polymer and starch on the tablet properties of
      lyophilized orally disintegrating tablet.
AB  - Orally disintegrating tablet (ODT) is a user friendly and convenient dosage form.
      The study aimed to investigate the effect of polymers and wheat starch on the
      tablet properties of lyophilized ODT, with dapoxetine as model drug. Three
      polymers (hydroxypropylmethyl cellulose, carbopol 934P and Eudragit(r) EPO) and
      wheat starch were used as matrix forming materials in preparation of lyophilized
      ODT. The polymeric dispersion was casted into a mould and kept in a freezer at 
      20  degrees C for 4 h before freeze dried for 12 h. It was found that increasing
      in HPMC and Carbopol 934P concentrations produced tablets with higher hardness
      and longer disintegration time. In contrast, Eudragit(r) EPO was unable to form
      tablet with sufficient hardness at various concentrations. Moreover, HPMC seems
      to have a stronger effect on tablet hardness compared to Carbopol 934P at the
      same concentration level. ODT of less friable was obtained. Wheat starch acted as
      binder which strengthen the hardness of ODTs and prolonged the disintegration
      time. ODT comprising of HPMC and wheat starch at ratio of 2:1 was found to be
      optimum based upon the tablet properties. The optimum formulation was palatable
      and 80 % of the drug was released within 30 min in the dissolution study.

PMID- 25579847
TI  - Is there a "metabolic-mood syndrome"? A review of the relationship between
      obesity and mood disorders.
AB  - Obesity and mood disorders are highly prevalent and co-morbid. Epidemiological
      studies have highlighted the public health relevance of this association, insofar
      as both conditions and its co-occurrence are associated with a staggering illness
      associated burden. Accumulating evidence indicates that obesity and mood
      disorders are intrinsically linked and share a series of clinical,
      neurobiological, genetic and environmental factors. The relationship of these
      conditions has been described as convergent and bidirectional; and some authors
      have attempted to describe a specific subtype of mood disorders characterized by
      a higher incidence of obesity and metabolic problems. However, the nature of this
      association remains poorly understood. There are significant inconsistencies in
      the studies evaluating metabolic and mood disorders; and, as a result, several
      questions persist about the validity and the generalizability of the findings. An
      important limitation in this area of research is the noteworthy phenotypic and
      pathophysiological heterogeneity of metabolic and mood disorders. Although
      clinically useful, categorical classifications in both conditions have limited
      heuristic value and its use hinders a more comprehensive understanding of the
      association between metabolic and mood disorders. A recent trend in psychiatry is
      to move toward a domain specific approach, wherein psychopathology constructs are
      agnostic to DSM-defined diagnostic categories and, instead, there is an effort to
      categorize domains based on pathogenic substrates, as proposed by the National
      Institute of Mental Health (NIMH) Research Domain Criteria Project (RDoC).
      Moreover, the substrates subserving psychopathology seems to be unspecific and
      extend into other medical illnesses that share in common brain consequences,
      which includes metabolic disorders. Overall, accumulating evidence indicates that
      there is a consistent association of multiple abnormalities in neuropsychological
      constructs, as well as correspondent brain abnormalities, with broad-based
      metabolic dysfunction, suggesting, therefore, that the existence of a "metabolic
      mood syndrome" is possible. Nonetheless, empirical evidence is necessary to
      support and develop this concept. Future research should focus on dimensional
      constructs and employ integrative, multidisciplinary and multimodal approaches. 

PMID- 25579846
TI  - Multiplex imaging and cellular target identification of kinase inhibitors via an
      affinity-based proteome profiling approach.
AB  - MLN8237 is a highly potent and presumably selective inhibitor of Aurora kinase A
      (AKA) and has shown promising antitumor activities. Like other kinase inhibitors
      which target the ATP-binding site of kinases, MLN8237 might be expected to have
      potential cellular off-targets. Herein, we report the first photoaffinity-based,
      small molecule AKA probe capable of both live-cell imaging of AKA activities and
      in situ proteome profiling of potential off-targets of MLN8237 (including AKA
      associating proteins). By using two mutually compatible, bioorthogonal reactions
      (copper-catalyzed azide-alkyne cycloaddition chemistry and TCO-tetrazine
      ligation), we demostrate small molecule-based multiplex bioimaging for
      simultaneous in situ monitoring of two important cell-cycle regulating kinases
      (AKA and CDK1). A broad range of proteins, as potential off-targets of MLN8237
      and AKA's-interacting partners, is subsequently identified by affinity-based
      proteome profiling coupled with large-scale LC-MS/MS analysis. From these
      studies, we discover novel AKA interactions which were further validated by cell
      based immunoprecipitation (IP) experiments. 

PMID- 25579849
TI  - The multifaceted factor peroxisome proliferator-activated receptor gamma
      (PPARgamma) in metabolism, immunity, and cancer.
AB  - The consumption of high-calorie foods combined with less physical exercise has
      increased the prevalence of obesity. Obesity is also associated with high blood
      pressure, atherosclerosis, insulin resistance, diabetes, impaired host defense,
      and the risk of some cancers. Because PPARgamma is a central player that
      participates in various biological responses, including lipid metabolism,
      inflammation, and cell proliferation, further understanding of the lipid
      metabolic sensor PPARgamma is necessary to reduce the incidence of metabolic
      diseases and cancer. 

PMID- 25579850
TI  - Sex-specific neuroanatomical correlates of fear expression in prefrontal-amygdala
      circuits.
AB  - BACKGROUND: The neural projections from the infralimbic region of the prefrontal
      cortex to the amygdala are important for the maintenance of conditioned fear
      extinction. Neurons in this pathway exhibit a unique pattern of structural
      plasticity that is sex-dependent, but the relationship between the morphologic
      characteristics of these neurons and successful extinction in male and female
      subjects is unknown. METHODS: Using classic cued fear conditioning and an
      extinction paradigm in large cohorts of male and female rats, we identified
      subpopulations of both sexes that exhibited high (HF) or low (LF) levels of
      freezing on an extinction retrieval test, representing failed or successful
      extinction maintenance, respectively. We combined retrograde tracing with
      fluorescent intracellular microinjections to perform three-dimensional
      reconstructions of infralimbic neurons that project to the basolateral amygdala
      in these groups. RESULTS: The HF and LF male rats exhibited neuroanatomical
      distinctions that were not observed in HF or LF female rats. A retrospective
      analysis of behavior during fear conditioning and extinction revealed that
      despite no overall sex differences in freezing behavior, HF and LF phenotypes
      emerged in male rats during extinction and in female rats during fear
      conditioning, which does not involve infralimbic-basolateral amygdala neurons.
      CONCLUSIONS: Our results suggest that the neural processes underlying successful
      or failed extinction maintenance may be sex-specific. These findings are relevant
      not only to future basic research on sex differences in fear conditioning and
      extinction but also to exposure-based clinical therapies, which are similar in
      premise to fear extinction and which are primarily used to treat disorders that
      are more common in women than in men.

PMID- 25579852
TI  - Vitamin B and its derivatives for diabetic kidney disease.
AB  - BACKGROUND: Diabetes is a leading cause of end-stage kidney disease (ESKD) mainly
      due to development and progression of diabetic kidney disease (DKD). In absence
      of definitive treatments of DKD, small studies showed that vitamin B may help in
      delaying progression of DKD by inhibiting vascular inflammation and endothelial
      cell damage. Hence, it could be beneficial as a treatment option for DKD.
      OBJECTIVES: To assess the benefits and harms of vitamin B and its derivatives in
      patients with DKD. SEARCH METHODS: We searched the Cochrane Renal Group's
      Specialised Register to 29 October 2012 through contact with the Trials' Search
      Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: We
      included randomised controlled trials comparing vitamin B or its derivatives, or
      both with placebo, no treatment or active treatment in patients with DKD. We
      excluded studies comparing vitamin B or its derivatives, or both among patients
      with pre-existing ESKD. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed study eligibility, risk of bias and extracted data. Results were
      reported as risk ratio (RR) or risk differences (RD) with 95% confidence
      intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for
      continuous outcomes. Statistical analyses were performed using the random-effects
      model. MAIN RESULTS: Nine studies compared 1354 participants randomised to either
      vitamin B or its derivatives with placebo or active control were identified. A
      total of 1102 participants were randomised to single vitamin B derivatives,
      placebo or active control in eight studies, and 252 participants randomised to
      multiple vitamin B derivatives or placebo. Monotherapy included different dose of
      pyridoxamine (four studies), benfotiamine (1), folic acid (1), thiamine (1), and
      vitamin B12 (1) while combination therapy included folic acid, vitamin B6, and
      vitamin B12 in one study. Treatment duration ranged from two to 36 months.
      Selection bias was unclear in three studies and low in the remaining six studies.
      Two studies reported blinding of patient, caregiver and observer and were at low
      risk of performance and detection bias, two studies were at high risk bias, and
      five studies were unclear. Attrition bias was high in one study, unclear in one
      study and low in seven studies. Reporting bias was high in one study, unclear in
      one study, and low in the remaining seven studies. Four studies funded by
      pharmaceutical companies were judged to be at high risk bias, three were at low
      risk of bias, and two were unclear.Only a single study reported a reduction in
      albuminuria with thiamine compared to placebo, while second study reported
      reduction in glomerular filtration rate (GFR) following use of combination
      therapy. No significant difference in the risk of all-cause mortality with
      pyridoxamine or combination therapy was reported. None of the vitamin B
      derivatives used either alone or in combination improved kidney function:
      increased in creatinine clearance, improved the GFR; neither were effective in
      controlling blood pressure significantly compared to placebo or active control.
      One study reported a significant median reduction in urinary albumin excretion
      with thiamine treatment compared to placebo. No significant difference was found
      between vitamin B combination therapy and control group for serious adverse
      events, or one or more adverse event per patient. Vitamin B therapy was reported
      to well-tolerated with mild side effects in studies with treatment duration of
      more than six months. Studies of less than six months duration did not explicitly
      report adverse events; they reported that the drugs were well-tolerated without
      any serious drug related adverse events. None of the included studies reported
      cardiovascular death, progression from macroalbuminuria to ESKD, progression from
      microalbuminuria to macroalbuminuria, regression from microalbuminuria to
      normoalbuminuria, doubling of SCr, and quality of life. We were not able to
      perform subgroup or sensitivity analyses or assess publication bias due to
      insufficient data. AUTHORS' CONCLUSIONS: There is an absence of evidence to
      recommend the use of vitamin B therapy alone or combination for delaying
      progression of DKD. Thiamine was found to be beneficial for reduction in
      albuminuria in a single study; however, there was lack of any improvement in
      kidney function or blood pressure following the use of vitamin B preparations
      used alone or in combination. These findings require further confirmation given
      the limitations of the small number and poor quality of the available studies.

PMID- 25579853
TI  - Starvation of cancer via induced ketogenesis and severe hypoglycemia.
AB  - Neoplasms are highly dependent on glucose as their substrate for energy
      production and are generally not able to catabolize other fuel sources such as
      ketones and fatty acids. Thus, removing access to glucose has the potential to
      starve cancer cells and induce apoptosis. Unfortunately, other body tissues are
      also dependent on glucose for energy under normal conditions. However, in human
      starvation (or in the setting of diet-induced ketogenesis), the body "keto
      adapts" and glucose requirements of most tissues drop to almost nil. Exceptions
      include the central nervous system (CNS) and various other tissues which have a
      small but obligatory requirement of glucose. Our hypothesized treatment takes
      keto-adaptation as a prerequisite. We then propose the induction of severe
      hypoglycemia by depressing gluconeogenesis while administering glucose to the
      brain. Although severe hypoglycemia normally produces adverse effects such as
      seizure and coma, it is relatively safe following keto-adaptation. We hypothesize
      that our therapeutic hypoglycemia treatment has potential to rapidly induce tumor
      cell necrosis. 

PMID- 25579851
TI  - Moderate Alcohol Drinking and the Amygdala Proteome: Identification and
      Validation of Calcium/Calmodulin Dependent Kinase II and AMPA Receptor Activity
      as Novel Molecular Mechanisms of the Positive Reinforcing Effects of Alcohol.
AB  - BACKGROUND: Despite worldwide consumption of moderate amounts of alcohol, the
      neural mechanisms that mediate the transition from use to abuse are not fully
      understood. METHODS: Here, we conducted a high-throughput screen of the amygdala
      proteome in mice after moderate alcohol drinking (n = 12/group) followed by
      behavioral studies (n = 6-8/group) to uncover novel molecular mechanisms of the
      positive reinforcing properties of alcohol that strongly influence the
      development of addiction. RESULTS: Two-dimensional difference in-gel
      electrophoresis with matrix assisted laser desorption ionization tandem time-of
      flight identified 29 differentially expressed proteins in the amygdala of
      nondependent C57BL/6J mice following 24 days of alcohol drinking. Alcohol
      sensitive proteins included calcium/calmodulin-dependent protein kinase II alpha
      (CaMKIIalpha) and a network of functionally linked proteins that regulate neural
      plasticity and glutamate-mediated synaptic activity. Accordingly, alcohol
      drinking increased alpha-amino-3-hydroxy-5-methyl-4-isooxazole receptor (AMPAR)
      in central amygdala (CeA) and phosphorylation of AMPAR GluA1 subunit at a CaMKII
      locus (GluA1-Ser831) in CeA and lateral amygdala. Further, CaMKIIalpha-Thr286 and
      GluA1-Ser831 phosphorylation was increased in CeA and lateral amygdala of mice
      that lever-pressed for alcohol versus the nondrug reinforcer sucrose. Mechanistic
      studies showed that targeted pharmacologic inhibition of amygdala CaMKII or AMPAR
      activity specifically inhibited the positive reinforcing properties of alcohol
      but not sucrose. CONCLUSIONS: Moderate alcohol drinking increases the activity
      and function of plasticity-linked protein networks in the amygdala that regulate
      the positive reinforcing effects of the drug. Given the prominence of positive
      reinforcement in the etiology of addiction, we propose that alcohol-induced
      adaptations in CaMKIIalpha and AMPAR signaling in the amygdala may serve as a
      molecular gateway from use to abuse.

PMID- 25579861
TI  - Retracted: immunization coverage: role of sociodemographic variables.
AB  - [This retracts the article DOI: 10.1155/2013/607935.]. 

PMID- 25579854
TI  - Sirtuin function in aging heart and vessels.
AB  - Age is the most important risk factor for metabolic alterations and
      cardiovascular accidents. Although class III histone deacetylases, alias
      Sirtuins, have been appealed as "the fountain of youth" their role in longevity
      control and prevention of aging-associated disease is still under debate. Indeed,
      several lines of evidence indicate that sirtuin activity is strictly linked to
      metabolism and dependent on NAD(+) synthesis both often altered as aging
      progresses. During aging the cardiovascular system is attacked by a variety of
      environmental stresses, including those determined by high blood glucose and
      lipid levels, or by the presence of oxidized lipoproteins which, among others,
      determine important oxidative stress signals. In such a milieu, heart and vessels
      develop a functional impairment leading to atherosclerosis, ischemia, heart
      insufficiency and failure. Sirtuins, which are believed to have a positive impact
      on cardiovascular physiology and physiopathology, are distributed in different
      subcellular compartments including the nucleus, the cytoplasm and the
      mitochondria, where they regulate expression and function of a large variety of
      target genes and proteins. Remarkably, experimental animal models indicate
      resveratrol, the first natural compound described to positively regulate the
      activity of sirtuins, as able to protect the endothelium and the heart exposed to
      a variety of stress agents. This review will focus on the regulation and function
      of mammalian sirtuins with special attention paid to their role as cardiovascular
      "defenders" giving indication of their targets of potential relevance for the
      development of future therapeutics. This article is part of a Special Issue
      entitled CV Aging. 

PMID- 25579862
TI  - Managing interoperability and complexity in health systems.
AB  - In recent years, we have witnessed substantial progress in the use of clinical
      informatics systems to support clinicians during episodes of care, manage
      specialised domain knowledge, perform complex clinical data analysis and improve
      the management of health organisations' resources. However, the vision of fully
      integrated health information eco-systems, which provide relevant information and
      useful knowledge at the point-of-care, remains elusive. This journal Focus Theme
      reviews some of the enduring challenges of interoperability and complexity in
      clinical informatics systems. Furthermore, a range of approaches are proposed in
      order to address, harness and resolve some of the many remaining issues towards a
      greater integration of health information systems and extraction of useful or new
      knowledge from heterogeneous electronic data repositories. 

PMID- 25579863
TI  - The effect of negative pressure aging on the aggregation of Cu2O nanoparticles
      and its application to laser induced copper electrode fabrication.
AB  - The aggregation and dispersion of nanoparticles are critical problems in
      selective laser sintering. In this study, negative pressure aging was applied to
      resolve the aggregation of nanoparticles and a metal oxide reduction method used
      to make a well-dispersed nanoparticles in solvent. As a result, metal oxide
      nanoparticles were synthesized according to a grade of the aggregation and aging
      conditions found to provide well-dispersed nanoparticles in solvent with less re
      dissolution of the nanoparticles. Furthermore, a coating quality and
      characteristics of laser induced sintering were analyzed according to the grade
      of the aggregation. The coating quality was affected by the aggregation and the
      statistical dispersion of nanoparticles. The coating deposited by particles with
      a wide statistical dispersion has a better quality when compared with the coating
      prepared from particles with a narrow dispersion. The quality of laser sintered
      electrode depends on the aggregation but the dependency of the aggregation
      diminishes as the irradiation of the laser power is decreased. 

PMID- 25579864
TI  - Response to comment on Imamura et al. Plasma polyunsaturated fatty acid profile
      and delta-5 desaturase activity are altered in patients with type 2 diabetes.
      Metabolism 2014;63(11):1432-8.

PMID- 25579866
TI  - Long wavelength undulations dominate dynamics in large surfactant membrane
      patches.
AB  - By exposing microemulsions to small (80 nm diameter) and large (500 nm) disk
      shaped clay particles we were able to show the presence of long wavelength
      undulations that only occur for large membrane patches. A combination of small
      angle neutron scattering (SANS) and neutron spin echo (NSE) experiments have been
      applied to study microemulsions. These, consisting of D2O, d-decane and the
      surfactant C10E4, were used in connection with Laponite (small) and Nanofil
      (large) clay. To our knowledge our experiments show for the first time that the
      clay platelets induce lamellar ordering adjacent to the clay discs in the
      otherwise bicontinuous microemulsion. This is due to the fact that in purely
      structural investigations, radial averaging smears out the signature of the
      lamellar phase. For thermodynamically fluctuating membranes near interfaces the
      theory of Seifert predicts a cross-over of the dispersion relationship from k(2)
      to a k(3)-dependence. With the correlation length of the membrane patches being
      confined by the dimension of the clay platelets we were able to show that this in
      fact takes place but is only present for the larger Nanofil particles. 

PMID- 25579865
TI  - Activation of innate immunity modulates insulin sensitivity, glucose
      effectiveness and pancreatic beta-cell function in both African ancestry and
      European ancestry healthy humans.
AB  - OBJECTIVE: Insulin resistance is a risk factor for type 2 diabetes, and is
      associated with inflammatory cardiometabolic disease. Given differences between
      African ancestry (AA) and European ancestry (EA) in the epidemiology of type 2
      diabetes as well as in response to inflammatory stress, we investigated potential
      race differences in glucose homeostasis responses during experimental endotoxemia
      in humans. METHODS: Healthy volunteers (age 18-45 years, BMI 18-30 kg/m(2), 47%
      female, African-ancestry (AA, n=42) and European-ancestry (EA, n=106)) were
      recruited as part of the Genetics of Evoked Responses to Niacin and Endotoxemia
      (GENE) Study. Subjects underwent an inpatient endotoxin challenge (1 ng/kg LPS)
      and two frequently-sampled intravenous glucose tolerance tests (FSIGTT). Insulin
      and glucose values obtained during FSIGTT pre- and 24-hours post-LPS were
      analyzed using the minimal model. RESULTS: FSIGTT derived insulin sensitivity
      index (SI), disposition index (DI) and glucose effectiveness (SG) decreased
      significantly following LPS (p<0.0001) while the acute insulin response to
      glucose (AIR(g)) increased (p<0.0001). Although expected race differences were
      observed in glucose homeostasis parameters at baseline prior to LPS e.g., lower
      SI (2.5 vs. 4.1 MUU/L/min, p<0.0001) but higher AIR(g) (median 848 vs. 290
      MUU/L/min, p<0.0001) in AA vs. EA, the changes in glucose homeostasis responses
      to LPS were directionally and proportionally consistent across race e.g., SI
      median -35% in EA and -29% in AA and AIR(g) median +17% in EA and +26% in AA.
      CONCLUSION: Both EA and AA samples modulated glucose and insulin homeostasis
      similarly during endotoxemia. IMPLICATIONS: Race differences in response to
      environmental inflammatory stress are unlikely to be a substantial contributor to
      the observed difference in diabetes incidence and complications between EA and
      AA.

PMID- 25579867
TI  - Influence of the preparation method on the physicochemical properties of
      indomethacin and methyl-beta-cyclodextrin complexes.
AB  - The main objective of this study was to investigate different manufacturing
      processes claimed to promote inclusion complexation between indomethacin and
      cyclodextrins in order to enhance the apparent solubility and dissolution
      properties of indomethacin. Especially, the effectiveness of supercritical carbon
      dioxide processing for preparing solid drug-cyclodextrin inclusion complexes was
      investigated and compared to other preparation methods. The complexes were
      prepared by physical mixing, co-evaporation, freeze drying from aqueous solution,
      spray drying and supercritical carbon dioxide processing methods. The prepared
      complexes were then evaluated by scanning electron microscopy, differential
      scanning calorimetry, X-ray powder diffraction, solubility and dissolution
      studies. The method of preparation of the inclusion complexes was shown to
      influence the physicochemical properties of the formed complexes. Indomethacin
      exists in a highly crystalline solid form. Physical mixing of indomethacin and
      methyl-beta-cyclodextrin appeared not to reduce the degree of crystallinity of
      the drug. The co-evaporated and freeze dried complexes had a lower degree of
      crystallinity than the physical mix; however the lowest degree of crystallinity
      was achieved in complexes prepared by spray drying and supercritical carbon
      dioxide processing methods. All systems based on methyl-beta-cyclodextrin
      exhibited better dissolution properties than the drug alone. The greatest
      improvement in drug dissolution properties was obtained from complexes prepared
      using supercritical carbon dioxide processing, thereafter by spray drying, freeze
      drying, co-evaporation and finally by physical mixing. Supercritical carbon
      dioxide processing is well known as an energy efficient alternative to other
      pharmaceutical processes and may have application for the preparation of solid
      state drug-cyclodextrin inclusion complexes. It is an effective and economic
      method that allows the formation of solid complexes with a high yield, without
      the use of organic solvents and problems associated with their residues.

PMID- 25579868
TI  - A new biodegradable polythiourethane as controlled release matrix polymer.
AB  - The main aim of this paper is the synthesis and characterization of a new linear
      functional biodegradable polythiourethane-d,l-1,4-dithiothreitol-hexamethylene
      diisocyanate [PTU(DTT-HMDI)]. The SeDeM diagram has been obtained to investigate
      its suitability to be processed through a direct compression process.
      Furthermore, the ability of this polymer to act as controlled release matrix
      forming excipient has been studied. Four batches of matrices containing 10-40% of
      polymer and theophylline anhydrous as model drug have been manufactured. Release
      studies have been carried out using the paddle method and the polymer percolation
      threshold has been estimated. The principal parameters of the SeDeM Expert
      system, such as the parametric profile (mean radius) and the good compression
      index (IGC=4.59) for the polymer are very close to the values considered as
      adequate for direct compression even with no addition of flow agents.
      Furthermore, the results of the drug release studies show a high ability of the
      polymer to control the drug release. The excipient percolation threshold has been
      estimated between 20% and 30% w/w of polymer. 

PMID- 25579869
TI  - Spray-dried solid dispersions of nifedipine and
      vinylcaprolactam/vinylacetate/PEG6000 for compacted oral formulations.
AB  - The aim of this work was to investigate an alternative processing technology for
      a new polymeric solubilizer used mainly in hot melt extrusion. Poorly soluble
      nifedipine was co-processed through spray-drying with poly(vinyl caprolactam-co
      vinyl acetate-co-ethylene glycol) (PVCVAEG) in different ratios. The resulting
      spray-dried powders were formulated and compacted into tablets forms. Spray
      drying produced reduced smooth spherical particles with PVCVAEG and more rough
      surfaces without PVCVAEG. Crystallinity of the co-processed nifedipine with the
      polymeric solubilizer was reduced. Plasticization of the polymeric solubilizer
      was observed with increasing drug content. Diffraction patterns in the small
      angle region as well as transmission electron microscopy showed results
      supporting phase separation throughout the spray dried particles of high drug
      content. Compaction with PVCVAEG improved cohesiveness of spray-dried compacts.
      Heckel modeling showed that deformation of PVCVAEG containing powders was more
      plastic compared than brittle nifedipine powders. Dissolution kinetics of all
      spray-dried samples was improved compared to original nifedipine crystals. Co
      processed nifedipine with PVCVAEG did not show improved dissolution rate when
      compared to spray drying nifedipine alone. All though PVCVAEG is more commonly co
      processed with drugs by hot melt extrusion to produce solid dispersions, the
      results show that it also can be processed by spray drying to produce solid
      dispersions. PVCVAEG improved compactibility of formulated spray dried powders. 

PMID- 25579871
TI  - Supercapacitive behavior depending on the mesopore size of three-dimensional
      micro-, meso- and macroporous silicon carbide for supercapacitors.
AB  - Three-dimensional silicon carbide-based frameworks with hierarchical micro-, meso
      , and macroporous structures (3MPSiC) were prepared by a template method with
      subsequent carbonization via an aerosol spray drying method. The micropores were
      derived from partial vaporization of Si atoms during the carbonization process,
      whereas the meso- and macropores were generated by self-assembly of the structure
      directing agent and polystyrene latex spheres, respectively. The effect of the
      mesopore size on the electrochemical performance of 3MPSiC electrodes was
      evaluated by fabricating three types of 3MPSiC samples with different mesopore
      size by using three different structure directing agents (cetyltriethylammonium
      bromide (CTAB), polyethylene glycol hexadecyl ether (Brij56), and poly(ethylene
      glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P123)). The
      3MPSiC electrode prepared using Brij56 exhibited outstanding electrochemical
      performance with a specific capacitance of 336.5 F g(-1) at a scan rate of 5 mV
      s(-1) with 90.3% rate performance from 5 to 500 mV s(-1) in 1 M Na2SO4 aqueous
      electrolyte. The outstanding electrochemical performance is attributed to the
      ideal mesopore size that can effectively reduce resistant pathways for ion
      diffusion in the pores as well as provide a large accessible surface area for ion
      transport/charge storage. These encouraging results demonstrate the high
      potential of 3MPSiC prepared using Brij56 for application as a high-performance
      electrode material for supercapacitors. 

PMID- 25579870
TI  - Evaluation of Pharmacologic Prevention of Pancreatitis After Endoscopic
      Retrograde Cholangiopancreatography: A Systematic Review.
AB  - BACKGROUND & AIMS: There is controversy over the efficacy of pharmacologic agents
      for preventing pancreatitis after endoscopic retrograde cholangiopancreatography
      (PEP). We performed a systematic review of PEP pharmacoprevention to evaluate
      safety and efficacy. METHODS: We performed a systematic search of the literature
      for randomized controlled trials (RCTs) and meta-analyses of PEP
      pharmacoprevention through February 2014. After identifying relevant studies, 2
      reviewers each extracted information on study characteristics, clinical outcomes,
      and risk of bias. A research classification scale was developed to identify
      pharmacologic agents ready for clinical use, agents for which a confirmatory RCT
      should be considered a high priority, agents for which exploratory studies are
      still necessary, and agents for which additional research should be of low
      priority. Clinical and research recommendations for each agent were made by
      consensus after considering research classification results and other important
      factors such as magnitude of benefit, safety, availability, and cost. RESULTS:
      After screening 851 citations and 263 potentially relevant articles, 2 reviewers
      identified 85 RCTs and 28 meta-analyses that were eligible. On the basis of these
      studies, rectal nonsteroidal anti-inflammatory drugs were found to be appropriate
      for clinical use, especially for high-risk cases. Sublingual nitroglycerin, bolus
      administered somatostatin, and nafamostat were found to be promising agents for
      which confirmatory research is warranted. Additional research was found to be
      required to justify confirmatory RCTs for topical epinephrine, aggressive
      intravenous fluids, gabexate, ulinastatin, secretin, and antibiotics.
      CONCLUSIONS: On the basis of a systematic review, NSAIDs are appropriate for use
      in prevention of PEP, especially for high-risk cases. Additional research is
      necessary to clarify the role of other pharmacologic agents. These findings could
      inform future research and guide clinical decision-making and policy.

PMID- 25579872
TI  - Nanotopography and plasma treatment: redesigning the surface for vascular graft
      endothelialisation.
AB  - INTRODUCTION: Vascular graft materials in clinical use, such as
      polytetrafluoroethylene (PTFE) and Dacron, do not endothelialise and have low
      patency rates. The importance of an endothelial cell layer on the luminal surface
      of a vascular graft is well-known with surface topography and chemistry playing
      an important role. The aim of this study was to investigate the potential of
      plasma treatment and topographical structures on the luminal graft surface to
      enhance the self-endothelialisation potential of a nanocomposite vascular graft.
      METHODS: POSS-PCU is a polycarbonate urea urethane (PCU) with a nanoparticle,
      polyhedral oligomeric silsesquioxane (POSS) incorporated within it. Planar,
      microgrooved, and nanopit patterned polymer films were fabricated using
      photolithography, electron beam lithography, reactive ion etching, and
      replication by solvent casting. Films were then exposed to oxygen plasma
      treatment at different powers for a fixed time (40 W, 60 W, 80 W/60 seconds).
      Effects of plasma treatment were assessed using scanning electron microscopy,
      atomic force microscopy and water contact angle analysis. Human umbilical vein
      endothelial cell (HUVEC) proliferation and morphology were characterised using
      immunostaining, live/dead staining, and Coomassie blue staining. RESULTS:
      Successful embossing of the micro- and nanostructures was confirmed. Oxygen
      plasma treatment of the different samples showed that increasing power
      significantly increased the hydrophilicity of the samples (p < .0001). Improved
      HUVEC adhesion was seen on plasma modified compared with untreated samples (p <
      .0001). Coomassie blue staining showed that after 5 days, cells started to form
      monolayers and live/dead staining showed the cells were viable. Immunostaining
      showed that HUVECs expressed nitric oxide synthase on all topographies with focal
      adhesions appearing more pronounced on nanopit surfaces, showing retention of
      morphology and function. CONCLUSION: These encouraging results indicate a future
      important role for plasma treatment and nanotopography in the development of
      endothelialised vascular grafts.

PMID- 25579874
TI  - The true risk of early recurrent stroke: importance of cohort composition and
      index event definition.

PMID- 25579873
TI  - Prospective evaluation of post-implantation inflammatory response after EVAR for
      AAA: influence on patients' 30 day outcome.
AB  - OBJECTIVES: The aim was to prospectively evaluate post-implantation syndrome
      (PIS) after elective endovascular aneurysm repair (EVAR) of abdominal aortic
      aneurysms (AAAs) and to investigate its association with clinical and laboratory
      parameters and the clinical outcome of the patients. METHODS: From January 2010
      till June 2013, 214 consecutive patients treated electively by EVAR for AAA were
      prospectively included. PIS was defined according to systemic inflammatory
      response syndrome criteria. Adverse events included any major adverse
      cardiovascular events (MACE), acute renal failure, re-admission and death from
      any cause. RESULTS: PIS was diagnosed in 77 (34%) patients. Pre-operative white
      blood cell (WBC) count values (p < .001), endograft material (polyester) (p <
      .001), and heart failure (p = .03) were independent predictors of PIS. Mean post
      operative temperature (p < .001), length of hospital (p < .001) and intensive
      care unit (p = .008) stay, as well as maximum post-operative WBC count (p < .001)
      and hs-CRP values (p < .001) were significantly higher in the PIS group. Post
      operative hs-CRP (p = .001) and duration of fever (p = .02) independently
      predicted the occurrence of MACE. Post-operative hs-CRP (p = .004), maximum
      temperature (p = .03), and the presence of PIS (p = .01) were independent
      predictors of an adverse event during the first 30 days. A threshold of post
      operative hs-CRP value of 125 mg/L was highly associated with the occurrence of
      MACE, with a sensitivity of 82% and specificity of 75%. CONCLUSIONS: A systematic
      inflammatory response is observed in a significant number of patients after EVAR.
      The type of endograft material seems to play a significant role in this
      inflammatory process. The intensity of inflammation, as assessed mainly by the
      post-operative hs-CRP values, correlates with the presence of a cardiovascular or
      any other adverse event during the first 30 days after the procedure.

PMID- 25579875
TI  - Donning devices (foot slips and frames) enable elderly people with severe chronic
      venous insufficiency to put on compression stockings.
AB  - OBJECTIVE/BACKGROUND: Compression therapy is highly effective in the treatment of
      post-thrombotic syndrome and venous leg ulcer. On average, 50-60% of the patients
      cooperate with compression therapy. Therefore, it is necessary to improve the
      user-friendliness. This prospective study investigated whether the use of donning
      devices can contribute to improving user-friendliness. METHODS: Forty patients
      aged >65 years with severe chronic venous insufficiency (CVI; C4-C6) successively
      donned compression stockings in a randomized order: one 40 mmHg (CS40) or two
      superimposed 20 mmHg (CS20+20), each with open toe (CS-o-t) and closed toe (CS-c
      t), using donning devices (three foot slips for CS-o-t; two foot slips and three
      frames for CS-c-t). The study endpoint was that the stocking was completely
      donned and correctly positioned on the patient's leg. The success rate and its
      association with age, sex, first time versus second time user, body mass index,
      abdominal circumference, ability to reach the forefoot with the hand, and hand
      grip strength were analyzed. Additionally, subjective evaluation by the patients
      was performed. RESULTS: Without donning devices, success with CS40-c-t was 60%
      (24/40 patients) and with CS20+20-c-t 70% (28/40 patients) (p = .220). Using
      donning devices increased success rates significantly. With CS40-o-t the success
      rate was 88% (35/40 patients; p = .001) and with CS40-c-t it was 90% (36/40
      patients; p = .002). With CS20+20-o-t and CS20+20-c-t, the success rate was 88%
      (35/40 patients; p = .016). The proportion of patients who successfully used
      either CS40 or CS20+20 increased from 73% to 93%. Relevant for the patients'
      success was the ability to reach the forefoot with the hand, and hand grip
      strength. Subjectively, donning with a device was rated significantly better than
      without. CONCLUSION: Donning devices significantly improve the ability of elderly
      patients with CVI to don compression stockings successfully. However, there are
      differences in user-friendliness among the devices..

PMID- 25579876
TI  - A new murine model of sustainable and durable chronic critical limb ischemia
      fairly mimicking human pathology.
AB  - OBJECTIVE: To establish a chronic mouse model of critical limb ischemia (CLI)
      with in vivo and ex vivo validation, closely mimicking human pathology. METHODS:
      Swiss mice (n = 28) were submitted to sequential unilateral femoral (day 0) and
      iliac (day 4) ligatures. Ischemia was confirmed by clinical scores (tissue and
      functional damages) and methoxyisobutylisonitrile (MIBI) scintigraphies at days
      0, 4, 6, 10, 20, and 30. At days 10, 20, and 30, muscle mitochondrial
      respiration, calcium retention capacity (CRC), and production of reactive oxygen
      species (ROS) were investigated, together with transcripts of mitochondrial
      biogenesis and antioxidant enzymes. Histological analysis was also performed.
      RESULTS: Clinical and functional damage confirmed CLI. MIBI scintigraphies showed
      hypoperfusion of the ischemic limb, which remained stable until day 30.
      Mitochondrial respiration was impaired in ischemic muscles compared with controls
      (Vmax = 7.93 +/- 0.99 vs. 10.09 +/- 2.87 mmol/L O2/minute/mg dry weight [dw]; p =
      .01), together with impaired CRC (7.4 +/- 1.6 mmol/L minute/mg dw vs. 11.9 +/-
      0.9 mmol/L minute/mg dw; p < .001) and biogenesis (41% decrease in peroxisome
      proliferator-activated receptor gamma coactivator [PGC]-1alpha, 49% decrease in
      PGC-1beta, and 41% decrease in nuclear respiratory factor-1). Ischemic muscles
      also demonstrated increased production of ROS under electron paramagnetic
      resonance (0.084 +/- 0.029 vs. 0.051 +/- 0.031 mmol/L minute/mg dw; p = .03) and
      with dihydroethidium staining (3622 +/- 604 arbitrary units of fluorescence vs.
      1224 +/- 324; p < .01), decreased antioxidant enzymes (32% decrease in superoxide
      dismutase [SOD]1, 41% decrease in SOD2, and 49% decrease in catalase), and
      myopathic features (wider range in fiber size, rounded shape, centrally located
      nuclei, and smaller cross-sectional areas). All defects were stable over time.
      CONCLUSION: Sequential femoral and iliac ligatures closely mimic human
      functional, clinical, scintigraphic, and skeletal muscle mitochondrial
      characteristics, and could prove useful for testing therapeutic approaches.

PMID- 25579878
TI  - Is the porcelain throne to blame?

PMID- 25579877
TI  - Safety, clinical outcome, and fracture rate of femoropopliteal stenting using a
      4F compatible delivery system.
AB  - OBJECTIVE: To determine the safety, clinical outcome, and fracture rate of
      femoropopliteal interventions using 4F stents. METHODS: Between January 2010 and
      December 2011, 112 symptomatic patients were treated by stent implantation. Ten
      patients were lost to follow up; therefore, 102 patients (62 men; mean age 66.4
      +/- 10.1 years) were retrospectively analyzed. The indication for femoropopliteal
      revascularization was severe claudication (Rutherford-Becker score = 3) in 63
      (62%) patients and chronic critical limb ischemia (Rutherford-Becker score = 4-6)
      in 39 (38%). Follow up included palpation of peripheral pulses and measurement of
      ankle brachial index. In patients with suspected in-stent restenosis duplex
      ultrasonography was performed. In 2013, patients were asked to return for a
      fluoroscopic examination of the stents. RESULTS: 114 lesions (Trans-Atlantic
      InterSociety Consensus-C and D, n = 45) were treated with 119 stents (Astron
      Pulsar, n = 42; Pulsar-18, n = 77). Lesions were long (>=100 mm) in 49 cases and
      heavily calcified in 35. Stents were long (>=120 mm) in 46 cases. Ten stents were
      partially overlapped. The technical and clinical success rates were 100%. Two
      puncture related complications were noted, neither of which required surgical
      repair. Eleven patients died (myocardial infarction, n = 4; stroke, n = 2;
      cancer, n = 5) and nine patients underwent major amputation (above knee, n = 4).
      The primary patency rate was 83% at 6 months and 80% at 12 months. The primary
      assisted patency rate was 97% at 6 months and 94% at 12 months. The secondary
      patency rate was 86% at 6 months and 85% at 12 months. The prevalence of
      fractures was 26% (type III and IV, 10%) after an average follow up of 25 months.
      CONCLUSION: Femoropopliteal stenting using a 4F compatible delivery system can be
      accomplished with a low complication rate, acceptable fracture rate, and with
      similar 12 month patency and revascularization rates as their 6F counterparts.

PMID- 25579879
TI  - Olefins from biomass feedstocks: catalytic ester decarbonylation and tandem Heck
      type coupling.
AB  - With the goal of avoiding the need for anhydride additives, the catalytic
      decarbonylation of p-nitrophenylesters of aliphatic carboxylic acids to their
      corresponding olefins, including commodity monomers like styrene and acrylates,
      has been developed. The reaction is catalyzed by palladium complexes in the
      absence of added ligands and is promoted by alkali/alkaline-earth metal halides.
      Combination of catalytic decarbonylation and Heck-type coupling with aryl esters
      in a single pot process demonstrates the viability of employing a carboxylic acid
      as a "masked olefin" in synthetic processes. 

PMID- 25579880
TI  - Plasmid DNA primary recovery from E. coli lysates by depth bed microfiltration.
AB  - Recently, several studies have been published on the application of plasmid DNA
      (pDNA) in gene therapy and vaccine production. The bioprocess to obtain pDNA
      involves the steps of fermentation, primary recovery, secondary recovery and
      final purification. The pDNA primary recovery, which is the key step to the rest
      of the process, includes biomass separation, alkaline lysis and clarification of
      the lysate. In this work, the clarification by depth bed microfiltration of
      lysates of E. coli DH5alpha containing the plasmid pVAX1-NH36 was investigated.
      The studies were conducted using filter capsules with nominal 8.0 um pore size
      using fluxes of 0.0027 and 0.004 cm(3)/(cm(2)-s). The results were compared with
      the conventional clarification by centrifugation. A fiber coating model was used
      to describe the behavior of the microfiltration system. A 99 % of solids
      elimination of the lysates was achieved with depth bed filtration method. The
      removed solids occupied 23 and 43 % (for 4 and 6 cm(3)/min, respectively) of the
      void volume of the depth bed microfiltration capsule since an early breakthrough
      curve is characteristic of these processes. The depth bed microfiltration process
      for removal of solids from the cell lysate showed competitive results compared to
      clarification by centrifugation.

PMID- 25579881
TI  - Recent progress in molecular genetic studies on the carotenoid transport system
      using cocoon-color mutants of the silkworm.
AB  - The existence of tissue-specific delivery for certain carotenoids is supported by
      genetic evidence from the silkworm Bombyx mori and the identification of cocoon
      color mutant genes, such as Yellow blood (Y), Yellow cocoon (C), and Flesh cocoon
      (F). Mutants with white cocoons are defective in one of the steps involved in
      transporting carotenoids from the midgut lumen to the middle silk gland via the
      hemolymph lipoprotein, lipophorin, and the different colored cocoons are caused
      by the accumulation of specific carotenoids into the middle silk gland. The Y
      gene encodes carotenoid-binding protein (CBP), which is expected to function as
      the cytosolic transporter of carotenoids across the enterocyte and epithelium of
      the middle silk gland. The C and F genes encode the C locus-associated membrane
      protein, which is homologous to a mammalian high-density lipoprotein receptor-2
      (Cameo2) and scavenger receptor class B member 15 (SCRB15), respectively; these
      membrane proteins are expected to function as non-internalizing lipophorin
      receptors in the middle silk gland. Cameo2 and SCRB15 belong to the cluster
      determinant 36 (CD36) family, with Cameo2 exhibiting specificity not only for
      lutein, but also for zeaxanthin and astaxanthin, while SCRB15 seems to have
      specificity toward carotene substrates such as alpha-carotene and beta-carotene.
      These findings suggest that Cameo2 and SCRB15 can discriminate the chemical
      structure of lutein and beta-carotene from circulating lipophorin during uptake.
      These data provide the first evidence that CD36 family proteins can discriminate
      individual carotenoid molecules in lipophorin.

PMID- 25579882
TI  - A chain extension method for apocarotenoids; lycopene and lycophyll syntheses.
AB  - The novel C5 benzothiazolyl (BT) sulfone containing an acetal group was prepared
      as a building block for the chain-extension of apocarotenoids. The double Julia
      Kocienski olefination of the BT-sulfone with C10 2,7-dimethyl-2,4,6
      octatrienedial and deprotection of the resulting acetal groups efficiently
      produced C20 crocetin dial. The higher homologues of C30 and C40 apocarotenoids
      were prepared from C20 crocetin dial by the repeated application of the Julia
      Kocienski olefination of the C5 BT-sulfone and hydrolysis. The scopes of the
      Julia-Kocienski olefination in the total synthesis of carotenoid natural products
      were evaluated using the C10+C20+C10 coupling protocol. The olefination was
      sensitive to the steric factor and bulky C10 beta-cyclogeranyl BT-sulfone was not
      able to react with C20 crocetin dial, however, lycopene and lycophyll were
      efficiently produced by the Julia-Kocienski olefination of C10 geranyl BT-sulfone
      and hydroxygeranyl BT-sulfone, in which protection of the hydroxyl group was not
      necessary.

PMID- 25579883
TI  - Tauroursodeoxycholic acid prevents stress induced aggregation of proteins in
      vitro and promotes PERK activation in HepG2 cells.
AB  - Tauroursodeoxycholic acid (TUDCA) a bile salt and chemical chaperone reduces
      stress-induced aggregation of proteins; activates PERK [PKR (RNA-dependent
      protein kinase)-like ER (endoplasmic reticulum) kinase] or EIF2AK3, one of the
      hall marks of ER stress induced unfolded protein response (UPR) in human
      hepatoblastoma HepG2 cells; prevents heat and dithiothreitol (DTT) induced
      aggregation of BSA (bovine serum albumin), and reduces ANS (1-anilino-naphthalene
      8-sulfonate) bound BSA fluorescence in vitro. TUDCA inactivates heat treated, but
      not the native EcoR1 enzyme, and reduces heat-induced aggregation and activity of
      COX-1 (cyclooxygenase enzyme-1) in vitro. These findings suggest that TUDCA binds
      to the hydrophobic regions of proteins and prevents their subsequent aggregation.
      This may stabilize unfolded proteins that can mount UPR or facilitate their
      degradation through cellular degradation pathways. 

PMID- 25579884
TI  - Control of the ribulose 1,5-bisphosphate carboxylase/oxygenase activity by the
      chloroplastic glutathione pool.
AB  - The CO2-fixing activity of ribulose 1,5-bisphosphate carboxylase/oxygenase
      depends on the redox state of its cysteines. Disulfides like cystamine or 5,5'
      dithio-bis(2-nitrobenzoic acid), but not oxidized glutathione, switch the enzyme
      to the inactive oxidized form. Conversely, thiols like cysteamine, cysteine,
      dithiotreitol or 2-mercaptoethanol, but not reduced glutathione, recover
      enzymatic activity after a previous oxidation. Direct regulation of the
      carboxylase activity by the chloroplastic glutathione pool is hindered by kinetic
      barriers impeding access to the critical residues. However, reduced glutathione
      can drive the recovery of activity by means of minute amounts of smaller
      intermediary thiol/disulfide exchangers. In contrast, oxidized glutathione does
      not inactivate the enzyme even in the presence of these intermediaries. This
      asymmetrical effect should help to maintain the enzyme in the active form in
      vivo. 

PMID- 25579885
TI  - Anemia and reduced kidney function as risk factors for new onset of atrial
      fibrillation (from the Ibaraki prefectural health study).
AB  - Chronic kidney disease (CKD) is a potential independent risk factor for atrial
      fibrillation (AF). It remains unclear whether anemia is synergistically
      associated with increased risk of AF onset in subjects with CKD. We evaluated the
      association of kidney function, hemoglobin (Hb), and their combination with new
      onset AF in a population-based cohort study. We conducted a 15-year prospective
      cohort study of 132,250 Japanese subjects aged 40 to 79 years who participated in
      annual health checkups from 1993. Kaplan-Meier survival analysis was used to
      compare freedom from new-onset AF between groups classified by estimated
      glomerular filtration rate grade, Hb grade, and their combination. Cox
      proportional hazard model analysis was used to estimate hazard ratios (HRs) for
      new-onset AF. During a 13.8-year mean follow-up period, 1,232 (0.93%) subjects
      with new-onset AF were identified. Lower estimated glomerular filtration rate and
      lower Hb grades were significantly associated with a higher incidence of new
      onset AF. Multivariate HRs and 95% confidence intervals (CIs) of new-onset AF
      were 1.38 (1.21 to 1.56) for mild CKD group, 2.56 (2.09 to 3.13) for CKD group,
      and 1.50 (1.24 to 1.83) for anemia group. Borderline Hb level was not
      significantly associated with increased risk for new-onset AF (HR 1.07, CI 0.91
      to 1.25, p = 0.4284). In the model with interaction term between CKD and anemia,
      the risk was significantly higher (p = 0.0343 for the interaction) than that
      predicted by each factor independently. In conclusion, decreased kidney function
      and lower Hb level are associated with increased risk for new-onset AF,
      especially when both are present.

PMID- 25579886
TI  - Multicenter long-term validation of a minicourse in radiation-reducing techniques
      in the catheterization laboratory.
AB  - Patient radiation exposure in invasive cardiology is considerable. We aimed to
      investigate, in a multicenter field study, the long-term efficacy of an
      educational 90-minute workshop in cardiac invasive techniques with reduced
      irradiation. Before and at a median period of 2.5 months and 2.0 years after the
      minicourse (periods I, II, and III, respectively) at 5 German cardiac centers, 18
      interventionalists documented various radiation parameters for 10 coronary
      angiographies. The median patient dose area product (DAP) for periods I, II, and
      III amounted to 26.6, 12.2, and 9.6 Gy * cm(2), respectively. The short-term and
      long-term effects were related to shorter median fluoroscopy times (180, 138, and
      114 seconds), fewer radiographic frames (745, 553, and 417) because of fewer (11,
      11, and 10) and shorter (64, 52, and 44 frames/run) runs, consistent collimation,
      and restriction to an adequate image quality; both radiographic DAP/frame (27.7,
      17.3, and 18.4 mGy * cm(2)) and fluoroscopic DAP/second (26.6, 12.9, and 14.9 mGy
      * cm(2)) decreased significantly. Multivariate analysis over time indicated
      increasing efficacy of the minicourse itself (-55% and -64%) and minor influence
      of interventionist experience (-4% and -3% per 1,000 coronary angiographies,
      performed lifelong until the minicourse and until period III). In conclusion,
      autonomous self-surveillance of various dose parameters and feedback on
      individual radiation safety efforts supported the efficacy of a 90-minute course
      program toward long-lasting and ongoing patient dose reduction.

PMID- 25579887
TI  - Overview of the Food and Drug Administration circulatory system devices panel
      meetings on WATCHMAN left atrial appendage closure therapy.
AB  - The WATCHMAN left atrial appendage closure (LAAC) technology is a percutaneously
      delivered permanent cardiac implant placed in the LAA. This device is designed to
      reduce the risk of stroke and systemic embolism in warfarin-eligible patients
      with nonvalvular atrial fibrillation. The first circulatory system device panel
      reviewed the Embolic Protection in Patients With Atrial Fibrillation (PROTECT AF)
      study in 2009, and a "not approvable" letter was issued by the US Food and Drug
      Administration (FDA) based on safety concerns. Subsequently, the FDA,
      collaboratively with the sponsor, designed a new Prospective Randomized
      Evaluation of the WATCHMAN LAAC Device in Patients With Atrial Fibrillation
      Versus Long-Term Warfarin Therapy (PREVAIL) trial to address the earlier study
      limitations. A second panel was convened in December 2013 to review the results
      of PREVAIL and additional long-term follow-up data from PROTECT AF. The second
      panel voted favorably 13 to 1 that the benefits of the WATCHMAN LAAC therapy do
      outweigh the risks for use in patients who meet the criteria specified in the
      proposed indication. Subsequently, and during the premarket approval review,
      updated data from the PREVIAL study revealed more ischemic strokes in the
      WATCHMAN group, corresponding to a total of 13 ischemic strokes in the WATCHMAN
      group versus 1 in the control group. As a result of these strokes, the FDA called
      for a third panel to assess the benefit-risk profile of the WATCHMAN device. This
      summary aims to describe the discussions and recommendations made during the
      panel meetings.

PMID- 25579888
TI  - Reconstitution of natural killer cells in HLA-matched HSCT after reduced
      intensity conditioning: impact on clinical outcome.
AB  - Recent advances in the development of reduced-intensity conditioning (RIC) have
      allowed a broader range of patients to access allogeneic hematopoietic stem cell
      transplantation (HSCT). Reconstitution of an effective immune system post
      transplant, including natural killer (NK) cells, is critical for both tumor
      control and infectious disease control or prevention. The development and
      functions of NK cells in such settings remain elusive. Here we analyzed NK cell
      development in HLA-matched HSCT from related or unrelated donors, after RIC that
      included antithymocyte globulin (N = 45 patients). Our data reveal that NK cells
      quickly recover after RIC-HSCT, irrespective of donor type. Rapidly re-emerging
      NK cells, however, remain immature for more than 6 months. Effector functions
      resemble that of immature NK cells because they poorly produce IFN-gamma and TNF
      alpha in response to target cell stimulation, despite a rapid acquisition of
      degranulation ability and MIP-1beta production. Strikingly, rapid reconstitution
      of cytokine production correlates with a lower relapse incidence (P = .01) and a
      better survival rate (P < .0001) at 1 year post-transplant, whereas degranulation
      capacity was associated with less relapse (P = .05). Our study demonstrates rapid
      quantitative reconstitution of the NK cell compartment despite administration of
      potent immune suppressive drugs as part of the conditioning regimen and after
      transplantation. However, there is a prolonged persistence of functional defects,
      the correction of which positively correlates with clinical outcome.

PMID- 25579889
TI  - Preparation and antibacterial activity of quaternized chitosan with iodine.
AB  - Chitosan (CTS) is a natural polymer with active groups such as -NH2 which can be
      functionalized to introduce new positively charged N-atoms and protonated amino
      group for better use. In this study, to improve the stability of iodine, a novel
      complex (CTS-CTA-I2) was prepared by mixing N-(2-hydroxy) propyl-3
      trimethylammonium chitosan chloride (CTS-CTA) with iodine in ethanol solution.
      The CTS-CTA-I2 was characterized by Fourier transform infrared spectra (FTIR),
      Ultraviolet and visible (UV-vis) spectra and thermal gravimetric analysis (TG).
      Besides, the interaction of iodine with CTS-CTA was also studied. The mole ratio
      of CTS-CTA with iodine was measured by iodometric titration method and the max
      mole ratio of CTS-CTA with iodine was 1:1.33. The antimicrobial activity of CTS,
      CTS-CTA and CTS-CTS-I2 complexes was investigated against Escherichia coli and
      Staphylococcus aureus and the antibacterial property of CTS-CTA-I2 was superior
      to CTS-CTA. 

PMID- 25579890
TI  - Nanoscale crystallinity modulates cell proliferation on plasma sprayed surfaces.
AB  - Calcium phosphate coatings have been applied to the surface of metallic
      prostheses to mediate hard and soft tissue attachment for more than 40years. Most
      coatings are formed of high purity hydroxyapatite, and coating methods are often
      designed to produce highly crystalline surfaces. It is likely however, that
      coatings of lower crystallinity can facilitate more rapid tissue attachment since
      the surface will exhibit a higher specific surface area and will be considerably
      more reactive than a comparable highly crystalline surface. Here we test this
      hypothesis by growing a population of MC3T3 osteoblast-like cells on the surface
      of two types of hip prosthesis with similar composition, but with differing
      crystallinity. The surfaces with lower crystallinity facilitated more rapid cell
      attachment and increased proliferation rate, despite having a less heterogeneous
      surface topography. This work highlights that the influence of the crystallinity
      of HA at the nano-scale is dominant over macro-scale topography for cell adhesion
      and growth. Furthermore, crystallinity could be easily adjusted by without
      compromising coating purity. These findings could facilitate designing novel
      coated calcium phosphate surfaces that more rapidly bond tissue following
      implantation. 

PMID- 25579891
TI  - Superelastic properties of biomedical (Ti-Zr)-Mo-Sn alloys.
AB  - A new class of Ti-50Zr base biomedical superelastic alloys was developed in this
      study. The (Ti-Zr)-Mo-Sn alloys exhibited a shape memory effect and superelastic
      property by adjusting Mo and Sn contents. The (Ti-Zr)-1.5Mo-3Sn alloy revealed
      the most stable superelasticity among (Ti-Zr)-(1-2)Mo-(2-4)Sn alloys. The
      superelastic recovery strain showed a strong dependence on heat treatment
      temperature after cold working in the (Ti-Zr)-1.5Mo-3Sn alloy. The superelastic
      recovery strain increased as the heat treatment temperature increased although
      the critical stress for slip decreased. The (Ti-Zr)-1.5Mo-3Sn alloy heat treated
      at 1073K exhibited excellent superelastic properties with a large recovery strain
      as large as 7% which is due to the strong {001}beta<110>beta recrystallization
      texture. 

PMID- 25579892
TI  - In vivo assessments of bioabsorbable AZ91 magnesium implants coated with
      nanostructured fluoridated hydroxyapatite by MAO/EPD technique for biomedical
      applications.
AB  - Although magnesium (Mg) is a unique biodegradable metal which possesses
      mechanical property similar to that of the natural bone and can be an attractive
      material to be used as orthopedic implants, its quick corrosion rate restricts
      its actual clinical applications. To control its rapid degradation, we have
      modified the surface of magnesium implant using fluoridated hydroxyapatite (FHA:
      Ca10(PO4)6OH2-xFx) through the combined micro-arc oxidation (MAO) and
      electrophoretic deposition (EPD) techniques, which was presented in our previous
      paper. In this article, the biocompatibility examinations were conducted on the
      coated AZ91 magnesium alloy by implanting it into the greater trochanter area of
      rabbits. The results of the in vivo animal test revealed a significant
      enhancement in the biocompatibility of FHA/MAO coated implant compared to the
      uncoated one. By applying the FHA/MAO coating on the AZ91 implant, the amount of
      weight loss and magnesium ion release in blood plasma decreased. According to the
      histological results, the formation of the new bone increased and the
      inflammation decreased around the implant. In addition, the implantation of the
      uncoated AZ91 alloy accompanied by the release of hydrogen gas around the
      implant; this release was suppressed by applying the coated implant. Our study
      exemplifies that the surface coating of magnesium implant using a bioactive
      ceramic such as fluoridated hydroxyapatite may improve the biocompatibility of
      the implant to make it suitable as a commercialized biomedical product. 

PMID- 25579893
TI  - Understanding corrosion behavior of Mg-Zn-Ca alloys from subcutaneous mouse
      model: effect of Zn element concentration and plasma electrolytic oxidation.
AB  - Mg-Zn-Ca alloys are considered as suitable biodegradable metallic implants
      because of their biocompatibility and proper physical properties. In this study,
      we investigated the effect of Zn concentration of Mg-xZn-0.3Ca (x=1, 3 and 5wt.%)
      alloys and surface modification by plasma electrolytic oxidation (PEO) on
      corrosion behavior in in vivo environment in terms of microstructure, corrosion
      rate, types of corrosion, and corrosion product formation. Microstructure
      analysis of alloys and morphological characterization of corrosion products were
      conducted using x-ray computed tomography (micro-CT) and scanning electron
      microscopy (SEM). Elemental composition and crystal structure of corrosion
      products were determined using x-ray diffraction (XRD) and electron dispersive x
      ray spectroscopy (EDX). The results show that 1) as-cast Mg-xZn-0.3Ca alloys are
      composed of Mg matrix and a secondary phase of Ca2Mg6Zn3 formed along grain
      boundaries, 2) the corrosion rate of Mg-xZn-0.3Ca alloys increases with
      increasing concentration of Zn in the alloy, 3) corrosion rates of alloys treated
      by PEO sample are decreased in in vivo environment, and 4) the corrosion products
      of these alloys after in vivo tests are identified as brucite (Mg(OH)2),
      hydroxyapatite (Ca10(PO4)6(OH)2), and magnesite (MgCO3.3H2O). 

PMID- 25579894
TI  - Antimicrobial brass coatings prepared on poly(ethylene terephthalate) textile by
      high power impulse magnetron sputtering.
AB  - The goal of this work is to prepare antimicrobial, corrosion-resistant and low
      cost Cu65Zn35 brass film on poly(ethylene terephthalate) (PET) fabric by high
      power impulse magnetron sputtering (HIPIMS), which is known to provide high
      density plasma, so as to generate a strongly adherent film at a reduced substrate
      temperature. The results reveal that the brass film grows in a layer-plus-island
      mode. Independent of their deposition time, the obtained films retain a Cu/Zn
      elemental composition ratio of 1.86 and exhibit primarily an alpha copper phase
      structure. Oxygen plasma pre-treatment for 1min before coating can significantly
      increase film adhesion such that the brass-coated fabric of Grade 5 or Grade 4-5
      can ultimately be obtained under dry and wet rubbing tests, respectively.
      However, a deposition time of 1min suffices to provide effective antimicrobial
      properties for both Staphylococcus aureus and Escherichia coli. As a whole, the
      feasibility of using such advanced HIPIMS coating technique to develop durable
      antimicrobial textile was demonstrated. 

PMID- 25579895
TI  - Determination of mechanical and hydraulic properties of PVA hydrogels.
AB  - In this paper the identification of mechanical and hydraulic parameters of
      poly(vinyl alcohol) (PVA) hydrogels is described. The identification method
      follows the solution of inverse problem using experimental data from the
      unconfined compression test and the poroelastic creep model. The sensitivity
      analysis of the model shows significant dependence of the creep curves on
      investigated parameters. The hydrogels containing 22% PVA and 25% PVA were tested
      giving: the drained Youngs modulus of 0.71 and 0.9MPa; the drained Poisson's
      ratio of 0.18 and 0.31; and the permeability of 3.64.10(-15) and
      3.29.10(15)m(4)/Ns, respectively. The values of undrained Youngs modulus were
      determined by measuring short period deformation of samples in the unconfined
      tests. A discussion on obtained results is presented. 

PMID- 25579896
TI  - Electrochemical behavior of near-beta titanium biomedical alloys in phosphate
      buffer saline solution.
AB  - The electrochemical behavior of three different near-beta titanium alloys
      (composed by Ti, Nb and Sn) obtained by powder metallurgy for biomedical
      applications has been investigated. Different electrochemical and microscopy
      techniques were used to study the influence of the chemical composition (Sn
      content) and the applied potential on the microstructure and the corrosion
      mechanisms of those titanium alloys. The addition of Sn below 4wt.% to the
      titanium powder improves the microstructural homogeneity and generates an alloy
      with high corrosion resistance with low elastic modulus, being more suitable as a
      biomaterial. When the Sn content is above 4%, the corrosion resistance
      considerably decreases by increasing the passive dissolution rate; this effect is
      enhanced with the applied potential. 

PMID- 25579897
TI  - Gelatin porous scaffolds fabricated using a modified gas foaming technique:
      characterisation and cytotoxicity assessment.
AB  - The current study presents an effective and simple strategy to obtain stable
      porous scaffolds from gelatin via a gas foaming method. The technique exploits
      the intrinsic foaming ability of gelatin in the presence of CO2 to obtain a
      porous structure stabilised with glutaraldehyde. The produced scaffolds were
      characterised using physical and mechanical characterisation methods. The results
      showed that gas foaming may allow the tailoring of the 3-dimensional structure of
      the scaffolds with an interconnected porous structure. To assess the
      effectiveness of the preparation method in mitigating the potential cytotoxicity
      risk of using glutaraldehyde as a crosslinker, direct and in-direct cytotoxicity
      assays were performed at different concentrations of glutaraldehyde. The results
      indicate the potential of the gas foaming method, in the preparation of viable
      tissue engineering scaffolds. 

PMID- 25579899
TI  - Enhancing the versatility of alternate current biosusceptometry (ACB) through the
      synthesis of a dextrose-modified tracer and a magnetic muco-adhesive cellulose
      gel.
AB  - Alternate Current Biosusceptometry (ACB) is a promising bio-magnetic method,
      radiation free and easily performed used for gastric emptying exams. Due to
      development on its sensitivity level, interesting nature, noninvasiveness and low
      cost it has attracted a lot of attention. In this work, magnetic nanoparticles of
      Mn-Zn ferrite as well as dextrose-modified nanoparticles were synthesized to be
      used as possible tracers in ACB gastric emptying exams. In addition, a magnetic
      muco-adhesive gel was obtained by modifying the ferrite nanoparticles with
      cellulose. Based on in-vivo tests in rats, we show that the pure ferrite
      nanoparticles, whose isoelectric point was found to be at pH=3.2, present a great
      sensitivity to pH variations along the gastrointestinal tract, while the
      reduction of the isoelectric point by the dextrose modification leads to suitable
      nanoparticles for rapid gastric emptying examinations. On the other hand, the in
      vivo tests show that the muco-adhesive cellulose gel presents substantial stomach
      adhesion and is a potential drug delivery system easily traceable by the ACB
      system. 

PMID- 25579898
TI  - Development of nanofibrous scaffolds containing gum tragacanth/poly (epsilon
      caprolactone) for application as skin scaffolds.
AB  - Outstanding wound healing activity of gum tragacanth (GT) and higher mechanical
      strength of poly (epsilon-caprolactone) (PCL) may produce an excellent
      nanofibrous patch for either skin tissue engineering or wound dressing
      application. PCL/GT scaffold containing different concentrations of PCL with
      different blend ratios of GT/PCL was produced using 90% acetic acid as solvent.
      The results demonstrated that the PCL/GT (3:1.5) with PCL concentration of 20%
      (w/v) produced nanofibers with proper morphology. Scanning electron microscopy
      (SEM) and differential scanning calorimetry (DSC) were utilized to characterize
      the nanofibers. Surface wettability, functional groups analysis, porosity and
      tensile properties of nanofibers were evaluated. Morphological characterization
      showed that the addition of GT to PCL solution results in decreasing the average
      diameter of the PCL/GT nanofibers. However, the hydrophilicity increased in the
      PCL/GT nanofibers. Slight increase in melting peaks was observed due to the
      blending of PCL with GT nanofibers. PCL/GT nanofibers were used for in vitro cell
      culture of human fibroblast cell lines AGO and NIH 3T3 fibroblast cells. MTT
      assay and SEM results showed that the biocomposite PCL/GT mats enhanced the
      fibroblast adhesion and proliferation compared to PCL scaffolds. The
      antibacterial activity of PCL/GT and GT nanofibers against Staphylococcus aureus
      and Pseudomonas aeruginosa was also examined. 

PMID- 25579901
TI  - A highly selective dual mode detection of Fe3+ ion sensing based on 1,5
      dihydroxyanthraquinone in the presence of beta-cyclodextrin.
AB  - 1,5-Dihydroxyanthraquinone (1,5-DHAQ) and in the presence of beta-cyclodextrin
      (beta-CD) has been used to find Fe(3+) ion in aqueous solution by UV-visible and
      fluorescence spectroscopy. The chromo-fluorogenic probe undergoes absorption and
      emission intensity enhancement upon binding to Fe(3+) ion in pH~7 aqueous
      solutions. The enhancement of the chemosensor probe is attributed to a 1:1
      inclusion complex formation between beta-CD and 1,5-DHAQ, which has been utilized
      as the basis for selective detection of Fe(3+) ion. The chemosensors can be
      applied to the selectivity and sensitivity analysis which showed that the
      remarkable sensing limit of detection (LOD) was 7.3*10(-7)M (beta-CD/1,5
      DHAQ:Fe(3+)). The proposed chemosensors based on 1,5-DHAQ and in the presence of
      beta-CD has a good selectivity, sensitivity and potential application to the
      determination of Fe(3+) ion in environmental and biological systems. 

PMID- 25579900
TI  - Fluorescent labelling of DNA on superparamagnetic nanoparticles by a perylene
      bisimide derivative for cell imaging.
AB  - N,N'-Bis[tris-(2-aminoethyl) amine]-3,4,9,10-perylenetetracarboxylic diimide (PBI
      TRIS), nonfluorescent dye was used to fluorescent labelling of DNA. For this aim,
      (3-aminopropyl) triethoxysilane (APTS) modified superparamagnetic iron oxide
      nanoparticles (SPIONs) were synthesized to provide a suitable surface for binding
      of DNA. Amine functionalized nanoparticles showed a high immobilization capacity
      (82.70%) at 25mg of nanoparticle concentration for Calf thymus DNA. Binding
      capacity of PBI-TRIS to DNA-SPION was also found as 1.93MUM on 25mg of
      nanoparticles by using UV-vis spectroscopy. Binding of PBI-TRIS to DNA onto
      nanoparticles was also characterized by scanning electron microscopy and infrared
      spectroscopy. The confocal images of PBI-TRIS labelled DNA-SPION and breast cells
      were taken at 488 and 561.7nm of excitation wavelengths. Cell image was also
      compared with a commercial dye, DAPI at 403.7nm of excitation wavelength. Results
      showed that PBI-TRIS can be used for cell staining. 

PMID- 25579902
TI  - Formation of platinum-coated templates of insulin nanowires used in reducing 4
      nitrophenol.
AB  - Modern technology demands ever smaller and more efficient nanoparticles, wires
      and networks. The natural tendency for amyloid proteins to form fibrillar
      structures is leveraged in creating high aspect ratio, nano-sized protein fibers
      as scaffolds for metallized nanowires. The morphology of fibrils is influenced by
      induced strain during denaturing and early aggregation and subsequent fibril
      deposition with platinum leads to controlled catalyst surfaces based on the
      initial protein precipitate. Here we have created insulin fibrils with varying
      morphologies produced in the presence of heat and strain and investigated their
      metallization with platinum by TEM. The catalytic activity of the metal-coated
      protein fibrils was resolved by tracking the reaction kinetics of the conversion
      of 4-nitrophenol to 4-aminophenol in the presence of the produced nanowires using
      UV-Vis spectroscopy. The effects of fibril morphology and temperature on the
      pseudo-first-order kinetics of conversion are investigated. Conversion to 4
      aminophenol occurs on the order of minutes and is independent of temperature in
      the range tested (7 to 20 degrees C). Two regimes of conversion are identified,
      an early higher rate, followed by a slower later rate. 

PMID- 25579903
TI  - Ultrathin films of lipids to investigate the action of a flavonoid with cell
      membrane models.
AB  - Understanding the role of natural compounds whose pharmaceutical activity is
      associated with cell membranes is fundamental to comprehending the biochemical
      processes that occur on membrane surfaces. In this work, we examined the action
      of 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one, known as quercetin,
      QCT, in lipid Langmuir monolayers at the air-water interface, which served as a
      model for half of a membrane. The surface pressure-area isotherms for 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayers exhibited a
      noticeable shift to higher areas in the presence of the flavonoid, which
      indicated the incorporation of QCT into the monolayer and expansion of the film.
      Also the flavonoid incorporation diminishes the monolayer surface elasticity for
      DPPC and causes a relative decrease of the intensity for C-H stretch bands,
      pointing to a disruption of the packed order of DPPC. These results can be
      associated to the interaction between QCT and cell membrane surfaces during
      biochemical processes, which may influence its pharmaceutical properties. 

PMID- 25579904
TI  - Surface plasma functionalization influences macrophage behavior on carbon
      nanowalls.
AB  - The surfaces of carbon nanowall samples as scaffolds for tissue engineering
      applications were treated with oxygen or nitrogen plasma to improve their
      wettability and to functionalize their surfaces with different functional groups.
      X-ray photoelectron spectroscopy and water contact angle results illustrated the
      effective conversion of the carbon nanowall surfaces from hydrophobic to
      hydrophilic and the incorporation of various amounts of carbon, oxygen and
      nitrogen functional groups during the treatments. The early inflammatory
      responses elicited by un-treated and modified carbon nanowall surfaces were
      investigated by quantifying tumor necrosis factor-alpha and macrophage
      inflammatory protein-1 alpha released by attached RAW 264.7 macrophage cells.
      Scanning electron microscopy and fluorescence studies were employed to
      investigate the changes in macrophage morphology and adhesive properties, while
      MTT assay was used to quantify cell proliferation. All samples sustained
      macrophage adhesion and growth. In addition, nitrogen plasma treatment was more
      beneficial for cell adhesion in comparison with un-modified carbon nanowall
      surfaces. Instead, oxygen plasma functionalization led to increased macrophage
      adhesion and spreading suggesting a more activated phenotype, confirmed by
      elevated cytokine release. Thus, our findings showed that the chemical surface
      alterations which occur as a result of plasma treatment, independent of surface
      wettability, affect macrophage response in vitro. 

PMID- 25579905
TI  - Bioactive thermoresponsive polyblend nanofiber formulations for wound healing.
AB  - The rationale of this work is to develop new bioactive thermoresponsive polyblend
      nanofiber formulations for wound healing (topical). Various polymer compositions
      of thermoresponsive, poly(N-isopropylacrylamide), egg albumen and poly(epsilon
      caprolactone) blend solutions with and without a drug [gatifloxacin
      hydrochloride, Gati] were prepared. Non-woven nanofibers of various compositions
      were fabricated using an electrospinning technique. The morphology of the
      nanofibers was analyzed by an environmental scanning electron microscope. The
      morphology was influenced by the concentration of polymer, drug, and polymer
      blend composition. Fourier transform infrared spectroscopy analysis showed the
      shift in bands due to hydrogen ion interactions between polymers and drug.
      Thermogram of PNIPAM/PCL/EA with Gati recorded a shift in lower critical solution
      temperature (LCST) and glass transition temperature (Tg) of PNIPAM. Similarly Tg
      and melting temperature (Tm) of PCL were shifted. X-ray diffraction patterns
      recorded a decrease in the crystalline state of PCL nanofibers and transformed
      crystalline drug to an amorphous state. In vitro release study of nanofibers with
      Gati showed initial rapid release up to 10h, followed by slow and controlled
      release for 696h (29days). Nanofiber mats with Gati exhibited antibacterial
      properties to Staphylococcus aureus, supported suitable controlled drug release
      with in vitro cell viability and in vivo wound healing. 

PMID- 25579906
TI  - Potential of extracellular enzymes from Trametes versicolor F21a in Microcystis
      spp. degradation.
AB  - Studies have shown that microorganisms may be used to eliminate cyanobacteria in
      aquatic environments. The present study showed that the white-rot fungus Trametes
      versicolor F21a could degrade Microcystis aeruginosa. After T. versicolor F21a
      and Microcystis spp. were co-incubated for 60h, >96% of Microcystis spp. cells
      were degraded by T. versicolor F21a. The activities of extracellular enzymes
      showed that cellulase, beta-glucosidase, protease, and laccase were vital to
      Microcystis spp. degradation in the early stage (0h to 24h), while beta
      glucosidase, protease, laccase, and manganese peroxidase in the late stage (24h
      to 60h). The positive and significant correlation of the degradation rate with
      these enzyme activities indicated that these enzymes were involved in the
      degradation rate of Microcystis spp. cells at different phases. It suggested that
      the extracellular enzymes released by T. versicolor F21a might be vital to
      Microcystis spp. degradation. The results of this study may be used to develop
      alternative microbial control agents for cyanobacterial control. 

PMID- 25579907
TI  - Development and characterization of oral liposomes of vegetal ceramide based
      amphotericin B having enhanced dry solubility and solubility.
AB  - Despite the development of new antifungal, amphotericin B remains one of the most
      effective agents in the treatment of systemic fungal infections. Many patients
      exhibit nevertheless intolerance to amphotericin B at higher dosages and
      parenteral formulations present unlike per os ones, associated risks and high
      care cost. Free amphotericin B per os showed however an apparently poor
      absorption. In this study, we evaluate the potential of amphotericin B liposomes
      formulated with vegetal ceramides for oral administration. Ceramides, one of the
      constituents of cellular cytoplasmic membranes, constitute an important element
      in the construction and stability of their lipid bilayer. To fulfill this
      objective, vegetal ceramides, composed essentially of glucosylceramides, were
      firstly incorporated in various liposome preparations, entrapping or not
      amphotericin B, in comparison with phosphatidylcholine liposomes. Then, these
      preparations were introduced in an "Artificial-Stomach-Duodenum" model to improve
      their stability for oral administration. The formulation of amphotericin B
      liposomes containing ceramides presented a mean hydrodynamic size of about 200nm.
      We showed also that cholesterol and phospholipids are required to prevent drug
      leakage and to obtain lamellar structure respectively. In "Artificial-Stomach
      Duodenum" model, ceramides conferred to liposomes better membrane stability. In
      addition, ceramides did not alter their drug encapsulation yield being by 75%.
      This could be explained by the fact that ceramides as we proved, limited the
      detergent effect of bile salts on liposome membranes. 

PMID- 25579908
TI  - Nanomechanical characterization of heterogeneous and hierarchical biomaterials
      and tissues using nanoindentation: the role of finite mixture models.
AB  - Mechanical characterization of biological tissues and biomaterials at the nano
      scale is often performed using nanoindentation experiments. The different
      constituents of the characterized materials will then appear in the histogram
      that shows the probability of measuring a certain range of mechanical properties.
      An objective technique is needed to separate the probability distributions that
      are mixed together in such a histogram. In this paper, finite mixture models
      (FMMs) are proposed as a tool capable of performing such types of analysis.
      Finite Gaussian mixture models assume that the measured probability distribution
      is a weighted combination of a finite number of Gaussian distributions with
      separate mean and standard deviation values. Dedicated optimization algorithms
      are available for fitting such a weighted mixture model to experimental data.
      Moreover, certain objective criteria are available to determine the optimum
      number of Gaussian distributions. In this paper, FMMs are used for interpreting
      the probability distribution functions representing the distributions of the
      elastic moduli of osteoarthritic human cartilage and co-polymeric microspheres.
      As for cartilage experiments, FMMs indicate that at least three mixture
      components are needed for describing the measured histogram. While the mechanical
      properties of the softer mixture components, often assumed to be associated with
      Glycosaminoglycans, were found to be more or less constant regardless of whether
      two or three mixture components were used, those of the second mixture component
      (i.e. collagen network) considerably changed depending on the number of mixture
      components. Regarding the co-polymeric microspheres, the optimum number of
      mixture components estimated by the FMM theory, i.e. 3, nicely matches the number
      of co-polymeric components used in the structure of the polymer. The computer
      programs used for the presented analyses are made freely available online for
      other researchers to use. 

PMID- 25579909
TI  - Fabrication and characterization of ovalbumin films for wound dressing
      applications.
AB  - A great number of people suffer from burning injuries all around the world each
      year. Applying an appropriate wound dressing can promote new tissue formation,
      prevent losing water and inhibit invasion of infectious organisms. In this study,
      egg white with a long standing history, as a homemade remedy, was fabricated as a
      wound dressing for burn injuries. For this reason, ovalbumin films were cross
      linked by 1-ethyl-3-3-dimethyl aminopropyl carbodiimide hydrochloride (EDC) with
      different concentrations (1, 5 and 10mM) using three concentrations of ethanol.
      Physical-chemical characterizations including Fourier transform infrared
      spectroscopy (FTIR), gas transmission rate (GTR), tensile mechanical tests, water
      uptake and degradation rate were performed on the samples. The sample with 5mM
      crosslinking agent at 70% ethanol was considered as the optimized one with 417kPa
      of ultimate tensile strength, 64% elongation at break and 230% water uptake. In
      addition, biological evaluations conducted by MTT and live/dead assay indicated
      no sign of cyto-toxicity for all the samples. Moreover, scanning electron
      microscopy (SEM) showed that the fibroblast cells were well spread on the sample
      with the formation of filopodia. In conclusion, modified ovalbumin can be applied
      as the base material for fabrication of wound dressing and skin care products. 

PMID- 25579910
TI  - The optimal extracting process, manufacturing technique and biological evaluation
      of Lithospermum erythrorhizon microcapsules.
AB  - Lithospermum erythrorhizon has been proved to be anti-inflammatory, by recent
      studies. This study extracts L. erythrorhizon with ethanol at various solid
      liquid ratios (1:4, 1:6, 1:8, and 1:12), extraction temperatures (40 degrees C,
      50 degrees C, and 60 degrees C), and extraction times (4, 24 and 36h) in order to
      determine the optimal parameters. The optimal parameters are extracted and
      condensed into L. erythrorhizon extract; then the antibacterial property and cell
      compatibility of L. erythrorhizon extract are evaluated with various
      concentrations of L. erythrorhizon extract solution and different weights of L.
      erythrorhizon extract powder, respectively. The concentrations of solution are
      0.1mg/ml, 0.5mg/ml, 1.0mg/ml, and 2.0mg/ml and ethanol is chosen as the solvent,
      and different weights of powder are varied as 0.1mg, 1.0mg, 2.0mg, and 10mg. The
      cell viability test and animal study are performed on L. erythrorhizon
      microcapsules. The experiment results show that sodium alginate/pectin L.
      erythrorhizon (SPL) microcapsules possess a 120-hour drug release. The results of
      cell viability and animal study show that the L. erythrorhizon microcapsules
      (SPL) have good cell viability (99%) and can help in the wound healing process
      (the wound size reduction reaches 91.3% on Day 11). 

PMID- 25579911
TI  - Chondroitin sulphate-guided construction of polypyrrole nanoarchitectures.
AB  - Nanospheres, nanocones, and nanowires are three typical polypyrrole (PPy)
      nanoarchitectures and electrochemically polymerized with the dope of chondroitin
      sulphate (CS) in this study. CS, a functional biomacromolecule, guides the
      formation of PPy nanoarchitectures as the dopant and morphology-directing agent.
      Combined with our previous reported other PPy nanoarchitectures (such as nanotube
      arrays and nanowires), this work further proposed the novel mechanism of the
      construction of PPy/CS nanoarchitectures with the synergistic effect of CS
      molecular chains structure and the steric hindrance. Compared to the undoped PPy,
      MC3T3-E1 cells with PPy/CS nanoarchitectures possessed stronger proliferation and
      osteogenic differentiation capability. This suggests that PPy/CS
      nanoarchitectures have appropriate biocompatibility. Altogether, the
      nanoarchitectured PPy/CS may find application in the regeneration of bone defect.

PMID- 25579912
TI  - Silver nanoparticle-doped zirconia capillaries for enhanced bacterial filtration.
AB  - Membrane clogging and biofilm formation are the most serious problems during
      water filtration. Silver nanoparticle (Agnano) coatings on filtration membranes
      can prevent bacterial adhesion and the initiation of biofilm formation. In this
      study, Agnano are immobilized via direct reduction on porous zirconia capillary
      membranes to generate a nanocomposite material combining the advantages of
      ceramics being chemically, thermally and mechanically stable with nanosilver, an
      efficient broadband bactericide for water decontamination. The filtration of
      bacterial suspensions of the fecal contaminant Escherichia coli reveals highly
      efficient bacterial retention capacities of the capillaries of 8 log reduction
      values, fulfilling the requirements on safe drinking water according to the U.S.
      Environmental Protection Agency. Maximum bacterial loading capacities of the
      capillary membranes are determined to be 3*10(9)bacterialcells/750mm(2) capillary
      surface until back flushing is recommendable. The immobilized Agnano remain
      accessible and exhibit strong bactericidal properties by killing retained
      bacteria up to maximum bacterial loads of 6*10(8)bacterialcells/750mm(2)
      capillary surface and the regenerated membranes regain filtration efficiencies of
      95-100%. Silver release is moderate as only 0.8% of the initial silver loading is
      leached during a three-day filtration experiment leading to average silver
      contaminant levels of 100MUg/L. 

PMID- 25579913
TI  - Mechanical, material, and antimicrobial properties of acrylic bone cement
      impregnated with silver nanoparticles.
AB  - Prosthetic joint infection is one of the most serious complications that can lead
      to failure of a total joint replacement. Recently, the rise of multidrug
      resistant bacteria has substantially reduced the efficacy of antibiotics that are
      typically incorporated into acrylic bone cement. Silver nanoparticles (AgNPs) are
      an attractive alternative to traditional antibiotics resulting from their broad
      spectrum antimicrobial activity and low bacterial resistance. The purpose of this
      study, therefore, was to incorporate metallic silver nanoparticles into acrylic
      bone cement and quantify the effects on the cement's mechanical, material and
      antimicrobial properties. AgNPs at three loading ratios (0.25, 0.5, and 1.0%
      wt/wt) were incorporated into a commercial bone cement using a probe sonication
      technique. The resulting cements demonstrated mechanical and material properties
      that were not substantially different from the standard cement. Testing against
      Staphylococcus aureus and Staphylococcus epidermidis using Kirby-Bauer and time
      kill assays demonstrated no antimicrobial activity against planktonic bacteria.
      In contrast, cements modified with AgNPs significantly reduced biofilm formation
      on the surface of the cement. These results indicate that AgNP-loaded cement is
      of high potential for use in primary arthroplasty where prevention of bacterial
      surface colonization is vital. 

PMID- 25579914
TI  - Optimization of sustained release aceclofenac microspheres using response surface
      methodology.
AB  - Polymeric microspheres containing aceclofenac were prepared by single emulsion
      (oil-in-water) solvent evaporation method using response surface methodology
      (RSM). Microspheres were prepared by changing formulation variables such as the
      amount of Eudragit(r) RS100 and the amount of polyvinyl alcohol (PVA) by
      statistical experimental design in order to enhance the encapsulation efficiency
      (E.E.) of the microspheres. The resultant microspheres were evaluated for their
      size, morphology, E.E., and in vitro drug release. The amount of Eudragit(r)
      RS100 and the amount of PVA were found to be significant factors respectively for
      determining the E.E. of the microspheres. A linear mathematical model equation
      fitted to the data was used to predict the E.E. in the optimal region. Optimized
      formulation of microspheres was prepared using optimal process variables setting
      in order to evaluate the optimization capability of the models generated
      according to IV-optimal design. The microspheres showed high E.E. (74.14+/-0.015%
      to 85.34+/-0.011%) and suitably sustained drug release (minimum; 40% to 60%;
      maximum) over a period of 12h. The optimized microspheres formulation showed E.E.
      of 84.87+/-0.005 with small error value (1.39). The low magnitudes of error and
      the significant value of R(2) in the present investigation prove the high
      prognostic ability of the design. The absence of interactions between drug and
      polymers was confirmed by Fourier transform infrared (FTIR) spectroscopy.
      Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD)
      revealed the dispersion of drug within microspheres formulation. The microspheres
      were found to be discrete, spherical with smooth surface. The results demonstrate
      that these microspheres could be promising delivery system to sustain the drug
      release and improve the E.E. thus prolong drug action and achieve the highest
      healing effect with minimal gastrointestinal side effects. 

PMID- 25579915
TI  - A highly selective voltammetric sensor for nanomolar detection of mercury ions
      using a carbon ionic liquid paste electrode impregnated with novel ion imprinted
      polymeric nanobeads.
AB  - This work reports the preparation of a voltammetric sensor for selective
      recognition and sensitive determination of mercury ions using a carbon ionic
      liquid paste electrode (CILE) impregnated with novel Hg(2+)-ion imprinted
      polymeric nanobeads (IIP) based on dithizone, as a suitable ligand for complex
      formation with Hg(2+) ions. The differential pulse anodic stripping voltammetric
      technique was employed to investigate the performance of the prepared IIP-CILE
      for determination of hazardous mercury ions. The designed modified electrode
      revealed linear responses in the ranges of 0.5nM-10nM and 0.08MUM-2MUM with a
      limit of detection of 0.1nM (S/N=3). It was found that the peak currents of the
      modified electrode for Hg(2+) ions were at a maximum value in phosphate buffer of
      pH4.5. The optimized preconcentration potential and accumulation time were to be 
      0.9V and 35s, respectively. The applicability of the proposed sensor to mercury
      determination in waste water samples is reported. 

PMID- 25579916
TI  - Mercapto-ordered carbohydrate-derived porous carbon electrode as a novel
      electrochemical sensor for simple and sensitive ultra-trace detection of
      omeprazole in biological samples.
AB  - We are introducing mercapto-mesoporous carbon modified carbon paste electrode
      (mercapto-MP-C-CPE) as a new sensor for trace determination of omeprazole (OM) in
      biological samples. The synthesized modifier was characterized by
      thermogravimetry analysis (TGA), differential thermal analysis (DTA),
      transmission electron microscopy (TEM), Fourier transform infrared spectrometry
      (FT-IR), X-ray diffraction (XRD), elemental analysis (CHN) and N2 adsorption
      surface area measurement (BET). The electrochemical response characteristic of
      the modified-CPE toward OM was investigated by cyclic and differential pulse
      voltammetry (CV and DPV). The proposed sensor displayed a good electrooxidation
      response to the OM, its linear range is 0.25nM to 25MUM with a detection limit of
      0.04nM under the optimized conditions. The prepared modified electrode shows
      several advantages such as high sensitivity, long-time stability, wide linear
      range, ease of preparation and regeneration of the electrode surface by simple
      polishing and excellent reproducibility. 

PMID- 25579917
TI  - Antibacterial action mode of quaternized carboxymethyl chitosan/poly(amidoamine)
      dendrimer core-shell nanoparticles against Escherichia coli correlated with
      molecular chain conformation.
AB  - The action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer
      core-shell nanoparticles (CM-HTCC/PAMAM) against Escherichia coli (E. coli) was
      investigated via a combination of approaches including measurements of cell
      membrane integrity, outer membrane (OM) and inner membrane (IM) permeability, and
      scanning electron microscopy (SEM). CM-HTCC/PAMAM dendrimer nanoparticles likely
      acted in a sequent event-driven mechanism, beginning with the binding of
      positively charged groups from nanoparticle surface with negative cell surface,
      thereby causing the disorganization of cell membrane, and subsequent leakage of
      intracellular components which might ultimately lead to cell death. Moreover, the
      chain conformation of polymers was taken into account for a better understanding
      of the antibacterial action mode by means of viscosity and GPC measurements. High
      utilization ratio of positive charge and large specific surface area generated
      from a compacted conformation of CM-HTCC/PAMAM, significantly different from the
      extended conformation of HTCC, were proposed to be involved in the antibacterial
      action. 

PMID- 25579918
TI  - Microbiological influenced corrosion resistance characteristics of a 304L-Cu
      stainless steel against Escherichia coli.
AB  - Cu-bearing antibacterial stainless steels have been gaining popularity in recent
      years due to their strong antibacterial performances. However, only a few studies
      were reported for their actual performances against microbiologically influenced
      corrosion (MIC). In this study, electrochemical methods and surface analytical
      techniques were applied to study the MIC resistance characteristics of a 304L-Cu
      stainless steel (SS) against Escherichia coli in comparison with 304L SS as
      control. Corrosion tests for specimens after a 21-day exposure to a Luria-Bertani
      (LB) culture medium with E. coli demonstrated that the 304L-Cu SS considerably
      reduced the maximum MIC pit depth and the specific weight loss compared with 304L
      SS (8.3MUm and 0.2mg/cm(2) vs. 13.4MUm and 0.6mg/cm(2)). Potentiodynamic
      polarization tests showed that the corrosion current density of the 304L-Cu SS
      was as much as 4 times lower than that of the 304L SS, indicating that the 304L
      Cu SS is a better choice for applications in MIC-prone environments. 

PMID- 25579919
TI  - Electrooxidation behavior of warfarin in Fe3O4 nanoparticles modified carbon
      paste electrode and its determination in real samples.
AB  - In the present work, a simple and sensitive electrochemical sensor based on
      magnetic Fe3O4 nanoparticles modified carbon paste electrode (CPE) was introduced
      for detection of low level with 0.21MUM of warfarin. Under the optimum
      experimental conditions the oxidation peak current of warfarin was used for its
      monitoring for the first time. The analytical curve was linear for warfarin
      concentrations from 0.5 to 1000MUM with a limit of detection of 0.21MUM by square
      wave anodic stripping voltammetry (SWASV). The proposed sensor showed excellent
      stability and was used for the determination of warfarin in tablet, human serum
      and urine with satisfactory results. 

PMID- 25579920
TI  - Corrosion behavior of titanium boride composite coating fabricated on
      commercially pure titanium in Ringer's solution for bioimplant applications.
AB  - The boriding of commercially pure titanium was performed at 850 degrees C, 910
      degrees C, and 1050 degrees C for varied soaking periods (1, 3 and 5h) to enhance
      the surface properties desirable for bioimplant applications. The coating
      developed was characterized for the evolution of phases, microstructure and
      morphology, microhardness, and consequent corrosion behavior in the Ringer's
      solution. Formation of the TiB2 layer at the outermost surface followed by the
      TiB whiskers across the borided CpTi is unveiled. Total thickness of the
      composite layer on the substrates borided at 850, 910, and 1050 degrees C for 5h
      was found to be 19.1, 26.4, and 18.2MUm respectively which includes <3MUm thick
      TiB2 layer. The presence of TiB2 phase was attributed to the high hardness
      ~2968Hv15gf of the composite coating. The anodic polarization studies in the
      simulated body fluid unveiled a reduction in the pitting corrosion resistance
      after boriding the CpTi specimens. However, this value is >0.55VSCE
      (electrochemical potential in in-vivo physiological environment) and hence
      remains within the safe region. Both the untreated and borided CpTi specimens
      show two passive zones associated with different passivation current densities.
      Among the CpTi borided at various times and temperatures, a 3h treated shows
      better corrosion resistance. The corrosion of borided CpTi occurred through the
      dissolution of TiB2. 

PMID- 25579921
TI  - Cytocompatibility and early osseointegration of nanoTiO2-modified Ti-24 Nb-4 Zr
      7.9 Sn surfaces.
AB  - This study aimed to evaluate the cytocompatibility and early osseointegration of
      Ti-24 Nb-4 Zr-7.9 Sn (Ti-2448) surfaces that were modified with a nanoscale TiO2
      coating. The coating was fabricated using a hydrothermal synthesis method to
      generate nanoTiO2/Ti-2448. The surface characteristics of the samples were
      evaluated using scanning electron microscopy (SEM), energy dispersive
      spectrometry (EDS) and X-ray diffraction (XRD). The cytotoxicity of the
      fabricated nanoTiO2/Ti-2448 was determined using MTT assays. The proliferation
      and alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblasts cultured on
      nanoTiO2/Ti-2448 were compared with those cultured on Ti-2448. Disk-shaped
      implants were placed in Wistar rats. The histological sections were stained with
      haematoxylin and eosin (HE), and the histocompatibility was analysed at 4 and
      12weeks post-implantation. Cylindrical implants were embedded in Japanese white
      rabbits, and the histological sections were stained with HE and anti-TGF-beta1 to
      evaluate the histocompatibility and early osseointegration at 4, 12 and 26weeks
      post-implantation. NanoTiO2/Ti-2448 exhibited a rougher surface than did Ti-2448.
      NanoTiO2/Ti-2448 was determined to be non-cytotoxic. More osteoblasts and higher
      ALP activity were observed for nanoTiO2/Ti-2448 than Ti-2448 (p<0.05). Few
      inflammatory cells were detected around nanoTiO2/Ti-2448, and the expression of
      TGF-beta1 on nanoTiO2/Ti-2448 peaked at earlier time than that on Ti-2448. The
      results indicate that the cytocompatibility and early osseointegration were
      enhanced by the nanoTiO2 coating. 

PMID- 25579922
TI  - Structural characterization of biomedical Co-Cr-Mo components produced by direct
      metal laser sintering.
AB  - Direct metal laser sintering (DMLS) is a technique to manufacture complex
      functional mechanical parts from a computer-aided design (CAD) model. Usually,
      the mechanical components produced by this procedure show higher residual
      porosity and poorer mechanical properties than those obtained by conventional
      manufacturing techniques. In this work, a Co-Cr-Mo alloy produced by DMLS with a
      composition suitable for biomedical applications was submitted to hardness
      measurements and structural characterization. The alloy showed a hardness value
      remarkably higher than those commonly obtained for the same cast or wrought
      alloys. In order to clarify the origin of this unexpected result, the sample
      microstructure was investigated by X-ray diffraction (XRD), electron microscopy
      (SEM and TEM) and energy dispersive microanalysis (EDX). For the first time, a
      homogeneous microstructure comprised of an intricate network of thin epsilon
      (hcp)-lamellae distributed inside a gamma (fcc) phase was observed. The epsilon
      lamellae grown on the {111}gamma planes limit the dislocation slip inside the
      gamma (fcc) phase, causing the measured hardness increase. The results suggest
      possible innovative applications of the DMLS technique to the production of
      mechanical parts in the medical and dental fields. 

PMID- 25579923
TI  - Immobilized organoruthenium(II) complexes onto polyethyleneimine-wrapped carbon
      nanotubes/in situ formed gold nanoparticles as a novel electrochemical sensing
      platform.
AB  - The polyethyleneimine (PEI) wrapped multi-walled carbon nanotubes functionalized
      with a carboxylic acid group (CNTs-COOH) gold nanoparticle (AuNP)-modified gold
      (Au) electrode has been utilized as a platform to immobilize organoruthenium(II)
      complexes (ORC). The surface structure and composition of the sensor were
      characterized by scanning electron microscopy (SEM). Electrocatalytic reduction
      of iodate and nitrite on the surface of modified electrode was investigated with
      cyclic voltammetry, electrochemical impedance spectroscopy (EIS) and hydrodynamic
      voltammetry methods. The cyclic voltammetric results indicated the ability of
      AuNPs/PEI/CNT-COOH/ORC modified Au electrode to catalyze the reduction of this
      compound. AuNPs/PEI/CNTs-COOH nanocomposite combined the advantages of PEI-well
      dispersed CNTs-COOH and in situ formed AuNPs. 

PMID- 25579924
TI  - Hydroxyapatite formation on titania-based materials in a solution mimicking body
      fluid: Effects of manganese and iron addition in anatase.
AB  - Hydroxyapatite formation on the surfaces of implanted materials plays an
      important role in osteoconduction of bone substitutes in bone tissues. Titania
      hydrogels are known to instigate hydroxyapatite formation in a solution mimicking
      human blood plasma. To date, the relationship between the surface characteristics
      of titania and hydroxyapatite formation on its surface remains unclear. In this
      study, titania powders with varying surface characteristics were prepared by
      addition of manganese or iron to examine hydroxyapatite formation in a type of
      simulated body fluid (Kokubo solution). Hydroxyapatite formation was monitored by
      observation of deposited particles with scale-like morphology on the prepared
      titania powders. The effect of the titania surface characteristics, i.e., crystal
      structure, zeta potential, hydroxy group content, and specific surface area, on
      hydroxyapatite formation was examined. Hydroxyapatite formation was observed on
      the surface of titania powders that were primarily anatase, and featured a
      negative zeta potential and low specific surface areas irrespective of the
      hydroxy group content. High specific surface areas inhibited the formation of
      hydroxyapatite because calcium and phosphate ions were mostly consumed by
      adsorption on the titania surface. Thus, these surface characteristics of titania
      determine its osteoconductivity following exposure to body fluid. 

PMID- 25579925
TI  - Simple method for preparing glucose biosensor based on in-situ polypyrrole cross
      linked chitosan/glucose oxidase/gold bionanocomposite film.
AB  - A film of chitosan-polypyrrole-gold nanoparticles was fabricated by in-situ
      chemical synthesis method and its application in glucose biosensor was
      investigated. The obtained biosensor exhibited a high and reproducible
      sensitivity of 0.58MUA/mM, response time ~4s, linear dynamic range from 1 to
      20mM, correlation coefficient of R(2)=0.9981, and limit of detection (LOD), based
      on S/N ratio (S/N=3) of 0.068mM. A value of 1.83mM for the apparent Michaelis
      Menten constant was obtained. The resulting bio-nanocomposite provided a suitable
      environment for the enzyme to retain its bioactivity at considerably extreme
      conditions, and the decorated gold nanoparticles in the bio-nanocomposite offer
      good affinity to enzyme. 

PMID- 25579926
TI  - Lipid nanocarriers containing a levodopa prodrug with potential antiparkinsonian
      activity.
AB  - This paper describes the production, characterization and in vivo activity of
      lipid nanocarriers (LN) containing a levodopa prodrug (LD-PD) with therapeutic
      potential in Parkinson's disease. LD is the mainstay of the pharmacotherapy of
      Parkinson's disease. However, after a good initial response, motor fluctuations,
      dyskinesia and loss of efficacy, develop over time, partly due to oscillations in
      plasma and brain levels of the drug. LD-PD was produced with the aim of
      prolonging the pharmacological activity of LD. To improve solubility, and
      simultaneously provide a long lasting release and therapeutic efficacy, the
      prodrug was formulated in tristearin/lecithin LN. The obtained formulation was
      homogeneous in particle size and remained stable for up to 2months from
      preparation. For the three different tested LD concentrations, namely 1.25, 2.5
      and 5.0mg/ml, the morphological characterization revealed no substantial
      differences between unloaded and LD-PD loaded LN. The calorimetric test showed an
      interaction between the lipid phase and the loaded prodrug. In vitro studies
      using the dialysis method and enzymatic degradation procedure showed that the LD
      PD loaded LN provided a controlled prodrug release. Finally, two behavioural
      tests specific to akinesia (bar test) or akinesia/bradykinesia (drag test)
      performed in 6-hydroxydopamine hemilesioned mice (a model of Parkinson's disease)
      demonstrated that the LD-PD loaded LN attenuated parkinsonian disabilities,
      showing a slightly reduced maximal efficacy but a longer lasting action (up to
      24h) than an equal dose of LD. We conclude that LD-PD loaded LN may represent a
      future LD formulation useful in Parkinson's disease therapy. 

PMID- 25579927
TI  - Adhesion and growth of human bone marrow mesenchymal stem cells on precise
      geometry 3D organic-inorganic composite scaffolds for bone repair.
AB  - Engineering biomaterial scaffolds that promote attachment and growth of
      mesenchymal stem cells in three dimensions is a crucial parameter for successful
      bone tissue engineering. Towards this direction, a lot of research effort has
      focused recently into the development of three-dimensional porous scaffolds,
      aiming to elicit positive cellular behavior. However, the fabrication of three
      dimensional tissue scaffolds with a precise geometry and complex micro- and nano
      features, supporting cell in-growth remains a challenge. In this study we report
      on a positive cellular response of human bone marrow-derived (BM) mesenchymal
      stem cells (MSCs) onto hybrid material scaffolds consisting of methacryloxypropyl
      trimethoxysilane, zirconium propoxide, and 2-(dimethylamino)ethyl methacrylate
      (DMAEMA). First, we use Direct fs Laser Writing, a 3D scaffolding technology to
      fabricate the complex structures. Subsequently, we investigate the morphology,
      viability and proliferation of BM-MSCs onto the hybrid scaffolds and examine the
      cellular response from different donors. Finally, we explore the effect of the
      materials' chemical composition on cell proliferation, employing three different
      material surfaces: (i) a hybrid consisting of methacryloxypropyl
      trimethoxysilane, zirconium propoxide and 50mol% DMAEMA, (ii) a hybrid material
      comprising methacryloxypropyl trimethoxysilane and zirconium propoxide, and (iii)
      a purely organic polyDMAEMA. Our results show a strong adhesion of BM-MSCs onto
      the hybrid material containing 50% DMAEMA from the first 2h after seeding, and up
      to several days, and a proliferation increase after 14 and 21days, similar to the
      polystyrene control, independent of cell donor. These findings support the
      potential use of our proposed cell-material combination in bone tissue
      engineering. 

PMID- 25579928
TI  - Influence of modified polyester on the material properties of collagen-based
      biocomposites and in vitro evaluation of cytocompatibility.
AB  - The cytocompatibility of composite materials collagen
      (Col)/poly(hydroxyalkanoate) (PHA) and collagen/maleic anhydride-grafted PHA (PHA
      g-MA) was investigated in this study. Col was homogeneously dispersed in the PHA
      g-MA matrix as a result of condensation reactions. Mechanical characterisation
      indicated that the improved adhesion between Col and PHA-g-MA enhanced the
      tensile strength of the composite compared with that of PHA/Col. PHA-g-MA/Col
      composites were also more water-resistant than PHA/Col composites. Collagen and
      cell proliferation analysis indicated that PHA and PHA-g-MA and their composites
      were biocompatible with respect to FB proliferation. Cell-cycle and apoptosis
      assays by FBs on the PHA series composite samples were not affected by DNA
      content related to damage, i.e. rapid apoptosis/necrosis was not observed,
      demonstrating the potential of PHA/Col or PHA-g-MA/Col membranes for biomedical
      material applications. 

PMID- 25579929
TI  - Surface modification of investment cast-316L implants: microstructure effects.
AB  - Artificial femur stem of 316L stainless steel was fabricated by investment
      casting using vacuum induction melting. Different surface treatments: mechanical
      polishing, thermal oxidation and immersion in alkaline solution were applied.
      Thicker hydroxyapatite (HAP) layer was formed in the furnace-oxidized samples as
      compared to the mechanically polished ones. The alkaline treatment enhanced the
      precipitation of HAP on the samples. It was also observed that the HAP
      precipitation responded differently to the different phases of the
      microstructure. The austenite phase was observed to have more homogeneous and
      smoother layer of HAP. In addition, the growth of HAP was sometimes favored on
      the austenite phase rather than on ferrite phase. 

PMID- 25579930
TI  - Cannabinoid antagonist in nanostructured lipid carriers (NLCs): design,
      characterization and in vivo study.
AB  - This study describes the preparation, characterization, and in vivo evaluation in
      rats of nanostructured lipid carriers (NLCs) encapsulating rimonabant (RMN) as
      prototypical cannabinoid antagonist. A study was conducted in order to optimize
      NLC production by melt and ultrasonication method. NLCs were prepared by
      alternatively adding the lipid phase into the aqueous one (direct protocol) or
      the aqueous phase into the lipid one (reverse protocol). RMN-NLCs have been
      characterized by cryogenic transmission electron microscopy (cryo-TEM), X-ray,
      photon correlation spectroscopy (PCS) and sedimentation field flow fractionation
      (SdFFF). Reverse NLCs were treated with polysorbate 80. RMN release kinetics have
      been determined in vitro by dialysis method. In vivo RMN biodistribution in rats
      was evaluated after intranasal (i.n.) administration of reverse RMN-NLC. The
      reverse protocol enabled to prevent the lost of lipid phase and to achieve higher
      RMN encapsulation efficacy (EE) with respect to the direct protocol (98% w/w
      versus 67% w/w). The use of different protocols did not affect NLC morphology and
      dimensional distribution. An in vitro dissolutive release rate of RMN was
      calculated. The in vivo data indicate that i.n. administration of RMN by reverse
      NLC treated with polysorbate 80 increased RMN concentration in the brain with
      respect to the drug in solution. The nanoencapsulation protocol presented here
      appears as an optimal strategy to improve the low solubility of cannabinoid
      compounds in an aqueous system suitable for in vivo administration. 

PMID- 25579931
TI  - Mixed zirconia calcium phosphate coatings for dental implants: tailoring coating
      stability and bioactivity potential.
AB  - Enhanced coating stability and adhesion are essential for long-term success of
      orthopedic and dental implants. In this study, the effect of coating composition
      on mechanical, physico-chemical and biological properties of coated zirconia
      specimens is investigated. Zirconia discs and dental screw implants are coated
      using the wet powder spraying (WPS) technique. The coatings are obtained by
      mixing yttria-stabilized zirconia (TZ) and hydroxyapatite (HA) in various ratios
      while a pure HA coating served as reference material. Scanning electron
      microscopy (SEM) and optical profilometer analysis confirm a similar coating
      morphology and roughness for all studied coatings, whereas the coating stability
      can be tailored with composition and is probed by insertion and dissections
      experiments in bovine bone with coated zirconia screw implants. An increasing
      content of calcium phosphate (CP) resulted in a decrease of mechanical and
      chemical stability, while the bioactivity increased in simulated body fluid
      (SBF). In vitro experiments with human osteoblast cells (HOB) revealed that the
      cells grew well on all samples but are affected by dissolution behavior of the
      studied coatings. This work demonstrates the overall good mechanical strength,
      the excellent interfacial bonding and the bioactivity potential of coatings with
      higher TZ contents, which provide a highly interesting coating for dental
      implants. 

PMID- 25579932
TI  - Rheology of dispersions of xanthan gum, locust bean gum and mixed biopolymer gel
      with silicon dioxide nanoparticles.
AB  - Mixed xanthan gum (XG) and locust bean gum (LBG) biopolymers form thermally
      reversible gels of interest in tissue engineering and drug delivery. 1% solutions
      of XG, LBG and 1:1 ratio XG/LBG mixed gels (LX) containing silicon dioxide (SiO2)
      nanoparticles were rheologically characterized with respect to nanoparticle
      concentration and temperature. 10% nanoparticles in XG created larger domains of
      associated polymer, resulting in enhanced viscosity and viscoelastic moduli. In
      LBG with 10% particles, transient viscosity and a gel-sol transition occurred due
      to particle bridging and aggregation. In the LX gel, 10% SiO2 particles caused an
      increase in elasticity. When ramping temperature from 25 degrees C to 85 degrees
      C, the complex modulus for all solutions containing 10% SiO2 was relatively
      constant, indicating that nanoparticles counteracted the effect of temperature on
      the material properties. Understanding the influence of nanoparticle loading on
      material properties is necessary for biopolymer material development where
      property prediction and control are critical. 

PMID- 25579933
TI  - Evaluating structural and microstructural changes of PDMS-SiO2 hybrid materials
      after sterilization by gamma irradiation.
AB  - PDMS-SiO2 hybrid materials obtained by sol-gel process have been extensively
      studied over the past years due to its promising biomedical applications namely
      as bone substitutes, catheters, and drug delivery devices. Regardless of the
      intended biomedical application, all these materials should go through a
      sterilization process before interfacing with a living structure. However, it is
      unclear whether they undergo structural and microstructural changes when
      subjected to sterilization by gamma irradiation. This paper addresses this issue
      by showing that a sol-gel processed biomaterial based on the PDMS-CaO-SiO2 hybrid
      system suffers only small structural changes when submitted to a radiation dose
      of 25kGy, the dose usually recommended to achieve a Sterility Assurance Level of
      10(-6) when the natural contamination level and microorganism types cannot be
      calculated. The characterization was assessed by FT-IR, (29)Si-{(1)H} CP-MAS,
      thermal analysis (DTG), and SEM. 

PMID- 25579934
TI  - Agitation of amyloid proteins to speed aggregation measured by ThT fluorescence:
      a call for standardization.
AB  - This retrospective study of protein aggregation measured by Thioflavin T (ThT)
      fluorescence assay in published literature has assessed protein sensitivity to
      denaturing conditions that include elevated temperatures, fluctuations in pH, and
      concentration and, in particular, agitation to induce amyloid structure
      formation. The dynamic tracking of fluorescence shows a sigmoidal evolution as
      aggregates form; the resulting kinetics of association have been analyzed to
      explore the range of aggregation behavior which occurs based on environmental
      parameters. Comparisons between the experimental results of different groups have
      been historically difficult due to subtleties of experimental procedures
      including denaturing temperature, protein type and concentration, formulation
      differences, and how agitation is achieved. While it is clear that agitation has
      a strong influence on the driving force for aggregation, the use of magnetic
      stirring bar or shaker table rotational speed is insufficient to characterize the
      degree of turbulence produced during shear. The pathway forward in resolving
      dependence of aggregate formation on shear may require alternative methodologies
      or better standardization of the experimental protocols. 

PMID- 25579935
TI  - Analysis of cellular adhesion on superhydrophobic and superhydrophilic vertically
      aligned carbon nanotube scaffolds.
AB  - We analyzed GFP cells after 24h cultivated on superhydrophilic vertically aligned
      carbon nanotube scaffolds. We produced two different densities of VACNT scaffolds
      on Ti using Ni or Fe catalysts. A simple and fast oxygen plasma treatment
      promoted the superhydrophilicity of them. We used five different substrates, such
      as: as-grown VACNT produced using Ni as catalyst (Ni), as-grown VACNT produced
      using Fe as catalyst (Fe), VACNT-O produced using Ni as catalyst (NiO), VACNT-O
      produced using Fe as catalyst (FeO) and Ti (control). The 4',6-diamidino-2
      phenylindole reagent nuclei stained the adherent cells cultivated on five
      different analyzed scaffolds. We used fluorescence microscopy for image collect,
      ImageJ(r) to count adhered cell and GraphPad Prism 5(r) for statistical analysis.
      We demonstrated in crescent order: Fe, Ni, NiO, FeO and Ti scaffolds that had an
      improved cellular adhesion. Oxygen treatment associated to high VACNT density
      (group FeO) presented significantly superior cell adhesion up to 24h. However,
      they do not show significant differences compared with Ti substrates (control).
      We demonstrated that all the analyzed substrates were nontoxic. Also, we proposed
      that the density and hydrophilicity influenced the cell adhesion behavior. 

PMID- 25579936
TI  - In vitro antimicrobial activity of solution blow spun poly(lactic
      acid)/polyvinylpyrrolidone nanofibers loaded with Copaiba (Copaifera sp.) oil.
AB  - In this study poly(lactic acid) (PLA) and polyvinylpyrrolidone (PVP) micro- and
      nanofiber mats loaded with Copaiba (Copaifera sp.) oil were produced by solution
      blow spinning (SBS). The Copaiba (Copaifera sp.) oil was characterized by gas
      chromatography (GC). Neat PLA and four PLA/PVP blends containing 20% (wt.%) oil
      were spun and characterized by scanning electron microscopy (SEM) and by studying
      the surface contact angle, in vitro release rate, and antimicrobial activity. All
      compositions evaluated were able to produce continuous and smooth fibers by SBS.
      The addition of PVP increased fiber diameter, and decreased the surface contact
      angle. GC analysis demonstrated that the main component of the Copaiba oil was
      beta-caryophyllene, a known antimicrobial agent. In vitro release tests of
      Copaiba oil volatiles demonstrated a higher release rate in fibers containing
      PVP. Fiber mats made from blends containing higher amounts of PVP had greater
      antimicrobial action against Staphylococcus aureus. The results confirm the
      potential of the fiber mats for use in controlled drug release and could lead to
      promising applications in the biomedical field. 

PMID- 25579937
TI  - Concentration-dependent effects of fibronectin adsorbed on hydroxyapatite
      surfaces on osteoblast adhesion.
AB  - Fibronectin (Fn) is an essential protein that is involved in cell attachment,
      migration, and differentiation. It is known that the conformation of Fn changes
      depending on its surrounding environment or on the surface properties of the
      substrate to which it is adsorbed. Here, we show that Fn adopts different
      conformations in physiological solutions and can play different roles in
      osteoblast adhesion on hydroxyapatite (HAp) depending on its concentration. The
      results of in situ observations showed that the adsorption configuration of Fn
      was an oblate ellipsoidal structure at low concentrations and a fibrillar
      structure at high concentrations, suggesting that individual Fn molecules attach
      to HAp with a side-on or end-on orientation, under low and high concentrations,
      respectively. Osteoblasts adhered more to the HAp surface under low
      concentrations of adsorbed Fn than under high concentrations. These observations
      suggest that the Fn concentration gradient is important for regulating
      biomaterial-cell interactions in regenerative medicine. 

PMID- 25579938
TI  - Controlled release of doxorubicin from electrospun PEO/chitosan/graphene oxide
      nanocomposite nanofibrous scaffolds.
AB  - Polyethylene oxide (PEO)/chitosan (CS)/graphene oxide (GO) electrospun
      nanofibrous scaffolds were successfully developed via electrospinning process for
      controlled release of doxorubicin (DOX). The SEM analysis of nanofibrous
      scaffolds with different contents of GO (0.1, 0.2, 0.5 and 0.7wt.%) indicated
      that the minimum diameter of nanofibers was found to be 85nm for PEO/CS/GO 0.5%
      nanofibers. The pi-pi stacking interaction between DOX and GO with fine pores of
      nanofibrous scaffolds exhibited higher drug loading (98%) and controlled release
      of the DOX loaded PEO/CS/GO nanofibers. The results of DOX release from
      nanofibrous scaffolds at pH5.3 and 7.4 indicated strong pH dependence. The
      hydrogen bonding interaction between GO and DOX could be unstable under acidic
      conditions which resulted in faster drug release rate in pH5.3. The cell
      viability results indicated that DOX loaded PEO/CS/GO/DOX nanofibrous scaffold
      could be used as an alternative source of DOX compared with free DOX to avoid the
      side effects of free DOX. Thus, the prepared nanofibrous scaffold offers as a
      novel formulation for treatment of lung cancer. 

PMID- 25579939
TI  - Influence of excipients on characteristics and release profiles of poly(epsilon
      caprolactone) microspheres containing immunoglobulin G.
AB  - Protein instability during microencapsulation has been one of the major drawbacks
      of protein delivery systems. In this study, the effects of various excipients
      (poly vinyl alcohol, glucose, starch, heparin) on the stability of encapsulated
      human immunoglobulin G (IgG) in poly(epsilon-caprolactone) (PCL) microspheres and
      on microsphere characteristics were investigated before and after gamma
      sterilization. Microspheres formulated without any excipients and with glucose
      had a mean particle size around 3-4MUm whereas the mean particle sizes of other
      microspheres were around 5-6MUm. Use of PVA significantly increased the IgG
      loading and encapsulation efficiency of microspheres. After gamma-irradiation,
      IgG stability was mostly maintained in the microspheres with excipients compared
      to microspheres without any excipients. According to the MUBCA results,
      microspheres without any excipient showed a high initial burst release as well as
      a fast release profile among all groups. Presence of PVA decreased the loss in
      the activity of IgG released before (completely retained after 6h and 15.69% loss
      after 7days) and after gamma-irradiation (26.04% loss and 52.39% loss after 6h
      and 7days, respectively). The stabilization effect of PVA on the retention of the
      activity of released IgG was found more efficient compared to other groups
      formulated with carbohydrates. 

PMID- 25579940
TI  - The processing of Mg alloy micro-tubes for biodegradable vascular stents.
AB  - In this study, through a combination of hot extrusion, cold rolling and drawing,
      three Mg alloys, Mg-Nd-Zn-Zr (abbr. JDBM), AZ31 and WE43, were successfully
      fabricated into the high-quality micro-tubes with 3.00mm outer diameter and
      180MUm thickness for biodegradable stents. This processing method overcame the
      shortcoming of the poor workability of Mg alloys and could be applied to
      fabricate sufficiently long tubes with low dimensional errors within 2.8%.
      Microstructure observation demonstrated that the as-annealed JDBM, AZ31 and WE43
      micro-tubes had more uniformly distributed grains with an average size of
      10.9MUm, 12.9MUm and 15.0MUm, respectively. Tensile mechanical test results
      showed that the as-annealed JDBM, AZ31 and WE43 micro-tubes respectively
      exhibited the yield strength of 123MPa, 172MPa and 113MPa, and significantly
      different breaking elongation of 26%, 16% and 10%. The following SEM observation
      showed microvoid coalescence, quasi-cleavage and cleavage fracture, respectively.
      In addition, EBSD analyses revealed that the as-annealed AZ31 tubes had a strong
      texture component 21-1-0 with a low Schmid factor for basal slip, while JDBM and
      WE43 tubes respectively exhibited weak textures 101-0 and 101-0+202-1 with a
      similarly high Schmid factor for basal slip. 

PMID- 25579941
TI  - The biocomposite tube of a chaetopterid marine worm constructed with highly
      controlled orientation of nanofilaments.
AB  - The ultrastructure of the self-constructed tube housing of the bioluminescent
      marine worm, Chaetopterus sp. reveals that the bio-nanocomposite tube comprises
      of multiple non-woven plies of multi-axially oriented organic nanofilaments (o 50
      1100nm) cemented together by an unstructured organic matrix binder. The thin
      walled, impermeable tubes are bio-inspirational for conventional pipe technology.
      Orientation distribution analyses revealed that the dominant orientation angles
      of nanofilaments in the tube were 0 degrees , +/-45 degrees  and +/-65 degrees ,
      which correlate well with optimal winding angles for 'man-made' fibre reinforced
      composite pipes subjected to specific loading conditions. Such a use of high
      aspect ratio nanofilaments in multi-axial laminates would impart toughness and
      flexibility to the tube structure, and facilitate rapid tube growth. While the
      tube production mechanism is not entirely known at this stage, our time-lapse
      studies show that, contrary to generic assumptions in literature, the worm
      actively, rapidly and sporadically produces and expands the tube. 

PMID- 25579942
TI  - One-pot synthesis of water-soluble superparamagnetic iron oxide nanoparticles and
      their MRI contrast effects in the mouse brains.
AB  - Water-soluble superparamagnetic iron oxide nanoparticles (SPIONs) were
      synthesized by the thermal decomposition of iron (III) acetylacetonate
      (Fe(acac)3) in the mixture of poly(ethylene glycol) (PEG) and poly(ethylene
      imine) (PEI). The average sizes of the SPIONs are in the range of 6-12nm, which
      could be tuned by adjusting the synthesis temperature and molecular weight of
      PEI. Benefiting from the coating of hydrophilic PEG and PEI, the resulted SPIONs
      showed excellent colloidal stability in deionized water and other physiological
      buffers. The XRD patterns indicate that the obtained SPIONs are magnetite. The
      PEG/PEI-SPIONs exhibited high r2/r1 ratio. In vivo magnetic resonance imaging
      (MRI) of the mouse brains after intravenous injection of the SPIONs showed their
      good contrast effect. Considering the facile fabrication process and excellent
      imaging performance of the water soluble PEG-SPIONs and PEG/PEI-SPIONs, it is
      believed that the SPIONs will find great potential in advanced MRI. 

PMID- 25579943
TI  - Development of a novel fluorimetric bulk optode membrane based on meso-tetrakis(2
      hydroxynaphthyl) porphyrin (MTHNP) for highly sensitive and selective monitoring
      of trace amounts of Hg2+ ions.
AB  - The fluorescence spectra and response characteristics of two porphyrin compounds
      meso-tetrakis(2-hydroxynaphthyl) porphyrin and meso-tetra (2-thiophene) porphyrin
      (MTHNP) to Hg(2+) were investigated. MTHNP showed preferable fluorescence
      response to Hg(2+). Thereby, an efficient and selective fluorimetric optode
      membrane based on the fluorescence quenching of MTHNP for Hg(2+) ion
      determination at low concentration levels has been developed. The sensing
      membrane containing MTHNP reversibly responded to Hg(2+) with a working
      concentration range covering from 5.0*10(-9) to 1.25*10(-5)M with a relatively
      fast response time less than 3min. In addition to high stability, reversibility
      and reproducibility, the sensor showed extremely high selectivity toward Hg(2+)
      ion with respect to some alkali, alkaline earth and heavy metal ions. The limit
      of detection for Hg(2+) was 5.0*10(-9)M. The proposed fluorescent sensor was
      successfully applied to the direct determination of mercury content of biofenac
      eye drop, hair and different water samples. 

PMID- 25579944
TI  - Biofunctional composite coating architectures based on polycaprolactone and
      nanohydroxyapatite for controlled corrosion activity and enhanced
      biocompatibility of magnesium AZ31 alloy.
AB  - In this work a biofunctional composite coating architecture for controlled
      corrosion activity and enhanced cellular adhesion of AZ31 Mg alloys is proposed.
      The composite coating consists of a polycaprolactone (PCL) matrix modified with
      nanohydroxyapatite (HA) applied over a nanometric layer of polyetherimide (PEI).
      The protective properties of the coating were studied by electrochemical
      impedance spectroscopy (EIS), a non-disturbing technique, and the coating
      morphology was investigated by field emission scanning electron microscopy (FE
      SEM). The results show that the composite coating protects the AZ31 substrate.
      The barrier properties of the coating can be optimized by changing the PCL
      concentration. The presence of nanohydroxyapatite particles influences the
      coating morphology and decreases the corrosion resistance. The biocompatibility
      was assessed by studying the response of osteoblastic cells on coated samples
      through resazurin assay, confocal laser scanning microscopy (CLSM) and scanning
      electron microscopy (SEM). The results show that the polycaprolactone to
      hydroxyapatite ratio affects the cell behavior and that the presence of
      hydroxyapatite induces high osteoblastic differentiation. 

PMID- 25579945
TI  - Processing and characterization of powdered silk micro- and nanofibers by
      ultrasonication.
AB  - Silk derived from Bombyx mori silkworm cocoons was degummed in an aqueous sodium
      carbonate solution, and the resulting silk fibroin fibers were placed in an
      acidic aqueous solution and were treated with ultrasonication to obtain powdered
      micro- and nanofibers. The morphologies and spectral characteristics of these
      powdered silk fibers were investigated in detail. The shape, surface and
      structural features of the powdered fibers were affected by the ultrasonic power
      and media. Increasing the acidity of the ultrasonic solution and increasing the
      ultrasonic power increased the fiber breakage speed, resulting in shorter fiber
      lengths. Powdered microfibers could not be obtained in a formic acid solution,
      while powdered nanofibers whose diameter below 1MUm were obtained in a combined
      formic acid and hydrochloric acid ultrasonication solution. Observation via SEM
      and optical microscopy revealed that the microfiber diameters were approximately
      5-10MUm, and those of the nanofibers were approximately 30-120nm. The analysis of
      laser sizer showed that the microfiber sizes ranged mainly from 20 to 100MUm. FT
      IR and XRD spectra demonstrated that the relative amount of beta-sheets increased
      after the ultrasonic treatment. The epsilon-amino group content on the surface of
      the micro- and nanofibers increased significantly. These studies provide reliable
      methods for the preparation of nano-scale silk fibroin fibers by ultrasonication
      and open new avenues for the development of powdered silk fibers as advanced
      functional biomaterials. 

PMID- 25579946
TI  - Geometrically controlled tensile response of braided sutures.
AB  - Sutures are the materials used for wound closure that are caused by surgery or
      trauma. The main pre-requisite to the success of the suture is to obtain ultimate
      level of tensile properties with defined geometrical constraints. In this
      communication, the model for tensile properties of braided sutures has been
      proposed by elucidating the most important geometrical and material parameters.
      The model has accounted for the kinematical changes occurring in the braid and
      constituent strand geometries under defined level of strain. A comparison has
      been made between the theoretical and experimental results of stress-strain
      characteristics of braided sutures. 

PMID- 25579947
TI  - Functionalized PCL/HA nanocomposites as microporous membranes for bone
      regeneration.
AB  - In the present work, microporous membranes based on poly(epsilon-caprolactone)
      (PCL) and PCL functionalized with amine (PCL-DMAEA) or anhydride groups (PCL
      MAGMA) were realized by solvent-non solvent phase inversion and proposed for use
      in Guided Tissue Regeneration (GTR). Nanowhiskers of hydroxyapatite (HA) were
      also incorporated in the polymer matrix to realize nanocomposite membranes.
      Scanning Electron Microscopy (SEM) showed improved interfacial adhesion with HA
      for functionalized polymers, and highlighted substantial differences in the
      porosity. A relationship between the developed porous structure of the membrane
      and the chemical nature of grafted groups was proposed. Compared to virgin PCL,
      hydrophilicity increases for functionalized PCL, while the addition of HA
      influences significantly the hydrophilic characteristics only in the case of
      virgin polymer. A significant increase of in vitro degradation rate was found for
      PCL-MAGMA based membranes, and at lower extent of PCL-DMAEA membranes. The novel
      materials were investigated regarding their potential as support for cell growth
      in bone repair using multipotent mesenchymal stromal cells (MSC) as a model. MSC
      plated onto the various membranes were analyzed in terms of adhesion,
      proliferation and osteogenic capacity that resulted to be related to chemical as
      well as porous structure. In particular, PCL-DMAEA and the relative nanocomposite
      membranes are the most promising in terms of cell-biomaterial interactions. 

PMID- 25579948
TI  - Molecularly imprinted polymer based on MWCNT-QDs as fluorescent biomimetic sensor
      for specific recognition of target protein.
AB  - A novel molecularly imprinted optosensing material based on multi-walled carbon
      nanotube-quantum dots (MWCNT-QDs) has been designed and synthesized for its high
      selectivity, sensitivity and specificity in the recognition of a target protein
      bovine serum albumin (BSA). Molecularly imprinted polymer coated MWCNT-QDs using
      BSA as the template (BMIP-coated MWCNT-QDs) exhibits a fast mass-transfer speed
      with a response time of 25min. It is found that the BSA as a target protein can
      significantly quench the luminescence of BMIP-coated MWCNT-QDs in a concentration
      dependent manner that is best described by a Stern-Volmer equation. The KSV for
      BSA is much higher than bovine hemoglobin and lysozyme, implying a highly
      selective recognition of the BMIP-coated MWCNT-QDs to BSA. Under optimal
      conditions, the relative fluorescence intensity of BMIP-coated MWCNT-QDs
      decreases linearly with the increasing target protein BSA in the concentration
      range of 5.0*10(-7)-35.0*10(-7)M with a detection limit of 80nM. 

PMID- 25579949
TI  - Effects of secondary phase and grain size on the corrosion of biodegradable Mg-Zn
      Ca alloys.
AB  - The bio-corrosion behaviour of Mg-3Zn-0.3Ca (wt.%) alloy in simulated body fluid
      (SBF) at 37 degrees C has been investigated using immersion testing and
      electrochemical measurements. Heat treatment has been used to alter the grain
      size and secondary phase volume fraction; the effects of these on the bio
      corrosion behaviour of the alloy were then determined. The as-cast sample has the
      highest bio-corrosion rate due to micro-galvanic corrosion between the eutectic
      product (Mg+Ca2Mg6Zn3) and the surrounding magnesium matrix. The bio-corrosion
      resistance of the alloy can be improved by heat treatment. The volume fraction of
      secondary phases and grain size are both key factors controlling the bio
      corrosion rate of the alloy. The bio-corrosion rate increases with volume
      fraction of secondary phase. When this is lower than 0.8%, the dependence of bio
      corrosion rate becomes noticeable: large grains corrode more quickly. 

PMID- 25579950
TI  - Design and construction of polymerized-chitosan coated Fe3O4 magnetic
      nanoparticles and its application for hydrophobic drug delivery.
AB  - In this study, a novel hydrogel, chitosan (CS) crosslinked carboxymethyl-beta
      cyclodextrin (CM-beta-CD) polymer modified Fe3O4 magnetic nanoparticles was
      synthesized for delivering hydrophobic anticancer drug 5-fluorouracil (CS-CDpoly
      MNPs). Carboxymethyl-beta-cyclodextrin being grafted on the Fe3O4 nanoparticles
      (CDpoly-MNPs) contributed to an enhancement of adsorption capacities because of
      the inclusion abilities of its hydrophobic cavity with insoluble anticancer drugs
      through host-guest interactions. Experimental results indicated that the amounts
      of crosslinking agent and bonding times played a crucial role in determining
      morphology features of the hybrid nanocarriers. The nanocarriers exhibited a high
      loading efficiency (44.7+/-1.8%) with a high saturation magnetization of
      43.8emu/g. UV-Vis spectroscopy results showed that anticancer drug 5-fluorouracil
      (5-Fu) could be successfully included into the cavities of the covalently linked
      CDpoly-MNPs. Moreover, the free carboxymethyl groups could enhance the bonding
      interactions between the covalently linked CDpoly-MNPs and anticancer drugs. In
      vitro release studies revealed that the release behaviors of CS-CDpoly-MNPs
      carriers were pH dependent and demonstrated a swelling and diffusion controlled
      release. A lower pH value led to swelling effect and electrostatic repulsion
      contributing to the protonation amine impact of NH3(+), and thus resulted in a
      higher release rate of 5-Fu. The mechanism of 5-Fu encapsulated into the magnetic
      chitosan nanoparticles was tentatively proposed. 

PMID- 25579951
TI  - Tunable thermo-responsive hydrogels: synthesis, structural analysis and drug
      release studies.
AB  - Thermo-responsive hydrogel films, synthesized by UV-initiated radical
      polymerization, are proposed as delivery devices for non-steroidal anti
      inflammatory drugs (Diclofenac sodium and Naproxen). N-isopropylacrylamide and
      N,N'-ethylenebisacrylamide were chosen as thermo-sensitive monomer and
      crosslinker, respectively. Infrared spectroscopy was used to assess the
      incorporation of monomers into the network, and the network density of hydrogel
      films was found to strictly depend on both feed composition and film thickness.
      Calorimetric analyses showed negative thermo-responsive behaviour with
      shrinking/swelling transition values in the range 32.8-36.1 degrees C.
      Equilibrium swelling studies around the LCST allowed the correlation between the
      structural changes and the temperature variations. The mesh size, indeed, rapidly
      changed from a collapsed to a swollen state, with beneficial effects in
      applications such as size-selective permeation or controlled drug delivery, while
      the crosslinking degree, the film thickness, and the loading method deeply
      influenced the drug release profiles at 25 and 40 degrees C. The analysis of both
      3D-network structure, release kinetics and diffusional constraints at different
      temperatures was evaluated by mathematical modelling. 

PMID- 25579952
TI  - Factors influencing the elastic moduli, reversible strains and hysteresis loops
      in martensitic Ti-Nb alloys.
AB  - While the current research focus in the search for biocompatible low-modulus
      alloys is set on beta-type Ti-based materials, the potential of fully martensitic
      Ti-based alloys remains largely unexplored. In this work, the influence of
      composition and pre-straining on the elastic properties of martensitic binary Ti
      Nb alloys was studied. Additionally, the phase formation was compared in the as
      cast versus the quenched state. The elastic moduli and hardness of the studied
      martensitic alloys are at a minimum of 16wt.% Nb and peak between 23.5 and
      28.5wt.% Nb. The uniaxial deformation behavior of the alloys used is
      characterized by the absence of distinct yield points. Monotonic and cyclic
      (hysteretic) loading-unloading experiments were used to study the influence of Nb
      content and pre-straining on the elastic moduli. Such experiments were also
      utilized to assess the recoverable elastic and anelastic deformations as well as
      hysteretic energy losses. Particular attention has been paid to the separation of
      non-linear elastic from anelastic strains, which govern the stress and strain
      limits to which a material can be loaded without deforming it plastically. It is
      shown that slight pre-straining of martensitic Ti-Nb alloys can lead to
      considerable reductions in their elastic moduli as well as increases in their
      total reversible strains. 

PMID- 25579953
TI  - Development of novel electrospun nanofibrous scaffold from P. Ricini And A.
      Mylitta silk fibroin blend with improved surface and biological properties.
AB  - Biomaterials that stimulate cell attachment and proliferation without any surface
      modification (e.g. RGD coating) provide potent and cost effective scaffold for
      regenerative medicine. This study assessed the physico-chemical properties and
      cell supportive potential of a silk fibroin blend scaffold derived from eri
      (Philosamia ricini) and tasar (Antheraea mylitta) silk (ET) respectively by
      electrospinning process. The scanning electron microscopy and transmission
      electron microscopy study found that the fiber diameters are in 200 to 800nm
      range with flat morphology. The porosity of ET scaffold is found to be 79+/-5%
      with majority of pore diameter between 2.5 to 5nm. Similarly, Bombyx mori (BM)
      silk fibroin and gelatin nanofibrous scaffolds were prepared and taken as
      control. The ultimate tensile strength of the ET and BM scaffold are found to be
      1.83+/-0.13MPa and 1.47+/-0.10MPa respectively. The measured contact angle (a
      measure of hydrophilicity) for ET (54.7 degrees +/-1.8 degrees ) is found to be
      lower than BM (62 degrees +/-2.3 degrees ). The ability to deposit apatite over
      ET is comparable to that of BM nanofibers. All the scaffolds were seeded with
      cord blood derived mesenchymal stem cells (hMSCs) and cultured for 14days in
      vitro. The immunofluorescence study reveals enhanced cell attachment with higher
      metabolic activity for MSCs grown over ET than BM and gelatin. The ET scaffold
      also demonstrated expression of higher amount cell adhesion molecules (CD29/CD44)
      and higher proliferation rate than BM and gelatin as confirmed by MTT assay, DNA
      content estimation assay, flow cytometry study and SEM study. Overall, it may be
      concluded that ET scaffold may have potential in developing bone tissue grafts
      for clinical applications in the future. 

PMID- 25579954
TI  - A novel poly(gamma-glutamic acid)/silk-sericin hydrogel for wound dressing:
      Synthesis, characterization and biological evaluation.
AB  - A novel multifunctional poly(gamma-glutamic acid)/silk sericin (gamma-PGA/SS)
      hydrogel has been developed and used as wound dressing. The physical and chemical
      properties of the gamma-PGA/SS gels were systemically investigated. Furthermore,
      these gamma-PGA/SS gels have been found to promote the L929 fibroblast cells
      proliferate, and in the in vivo study, significant stimulatory effects were also
      observed on granulation and capillary formation on day 9 in H-2-treated wounds,
      indicating that this new complex hydrogel could maintain a moist healing
      environment, protect the wound from bacterial infection, absorb excess exudates,
      and promote cell proliferation to reconstruct damaged tissue. Considering the
      simple preparation process and excellent biological property, this gamma-PGA/SS
      hydrogel might have a wide range of applications in biomedical and clinical
      areas. 

PMID- 25579955
TI  - Dual responsive dysprosium-doped hydroxyapatite particles and toxicity reduction
      after functionalization with folic and glucuronic acids.
AB  - The development of probes for biomedical applications demands materials with low
      toxicity levels besides fluorescence or magnetic properties to be detected by
      confocal microscopes or MRI resonators. Several drug delivery systems or other
      biomedical materials prepared with hydroxyapatite have been proposed, however,
      toxicity effects might arise when the size of particles is nanometric. In this
      study, hydroxyapatite functionalized with glucuronic or folic acids presented
      lower oxidative stress, measured from lipoperoxides and nitric oxide indicators
      in rats than pure hydroxyapatite. In separated experiments, hydroxyapatite was
      doped with dysprosium cations by coprecipitation producing a single crystal phase
      with fluorescent properties easily visualized by confocal microscopy when excited
      at 488nm. These particles also presented the ability to modify the proton
      relaxation time in T1 maps collected by magnetic resonance imaging. These
      modified hydroxyapatite nanoparticles could be candidates to design bimodal
      probes with low toxicity. 

PMID- 25579956
TI  - Influence of the polymer amount on bioactivity and biocompatibility of SiO2/PEG
      hybrid materials synthesized by sol-gel technique.
AB  - SiO2/PEG organic-inorganic hybrid materials, which differ in polyethylene glycol
      (PEG) content, were synthesized by sol-gel technique and the characterization of
      their structure and biological properties was carried out in order to evaluate
      the possible use in biomedical field. FT-IR spectroscopy detected that the two
      components of the hybrids (SiO2 and PEG) are linked by hydrogen bonds between the
      Si-OH groups of the inorganic phase and the terminal alcoholic groups and/or the
      ethereal oxygen atoms in the repeating units of polymer. X-ray diffraction
      analysis ascertained the amorphous nature of the gels and the observation of
      their morphology by SEM microscopy confirmed that the interpenetration of the two
      phases (organic and inorganic) occurs on nanometric scale. The biological
      characterization was carried out as a function of the polymer amount to study its
      influence on material behavior. The results showed that the synthesized materials
      were bioactive and biocompatible. The formation of a hydroxyapatite layer,
      indeed, was observed on their surface by SEM/EDX analysis after soaking in
      simulated body fluid. Moreover, the biocompatibility of SiO2/PEG hybrids was
      assessed performing MTT and SRB cytotoxicity tests on fibroblast cell NIH 3T3
      after 24 and 48h of exposure, as well as Trypan Blue dye exclusion test. The
      response to the presence of the investigated materials was positive. The cell
      growth and proliferation showed dependence on polymer amount and time of exposure
      to the material extracts. Therefore, the obtained results are encouraging for the
      use of the obtained hybrids in dental or orthopedic applications. 

PMID- 25579957
TI  - A review of: application of synthetic scaffold in tissue engineering heart
      valves.
AB  - The four heart valves represented in the mammalian hearts are responsible for
      maintaining unidirectional, non-hinder blood flow. The heart valve leaflets
      synchronically open and close approximately 4 million times a year and more than
      3 billion times during the life. Valvular heart dysfunction is a significant
      cause of morbidity and mortality around the world. When one of the valves
      malfunctions, the medical choice is may be to replace the original valves with an
      artificial one. Currently, the mechanical and biological artificial valves are
      clinically used with some drawbacks. Tissue engineering heart valve concept
      represents a new technique to enhance the current model. In tissue engineering
      method, a three-dimensional scaffold is fabricated as the template for neo-tissue
      development. Appropriate cells are seeded to the matrix in vitro. Various
      approaches have been investigated either in scaffold biomaterials and fabrication
      techniques or cell source and cultivation methods. The available results of
      ongoing experiments indicate a promising future in this area (particularly in
      combination of bone marrow stem cells with synthetic scaffold), which can
      eliminate the need for lifelong anti-coagulation medication, durability and
      reoperation problems. 

PMID- 25579958
TI  - UHMWPE-based nanocomposite as a material for damaged cartilage replacement.
AB  - In the present work dispersion-strengthened nanocomposites based on ultra-high
      molecular weight polyethylene (UHMWPE) after mechanical activation were studied.
      Mechanical activation was performed for hardening of the boundaries between the
      polymer particles, reducing the fusion defects and increasing of wear-resistance.
      Three types of samples were prepared: UHMWPE, UHMWPE/Al2O3 nanocomposite and
      UHMWPE/Al2O3 nanocomposite after mechanical activation. UHMWPE/Al2O3
      nanocomposites prepared with mechanical activation show the best mechanical
      properties in compression and higher wear-resistance. UHMWPE/Al2O3 nanocomposites
      prepared with mechanical activation were chosen for in vivo study by orthotopical
      transplantation in rats. Animals' activity has been being monitored for 60days
      after surgery. No signs of inflammation, cellular infiltration, destruction of
      material or bone-cartilage defect were found. Implanted sample has not changed
      its position of implantation, there were no any shifts. Obtained data shows that
      UHMWPE-based nanocomposite is a promising material for creating bioimplants for
      cartilage defect replacement. 

PMID- 25579959
TI  - The effect of nanobioceramic reinforcement on mechanical and biological
      properties of Co-base alloy/hydroxyapatite nanocomposite.
AB  - The goal of the present research was to fabricate, characterize, and evaluate
      mechanical and biological properties of Co-base alloy composites with different
      amounts of hydroxyapatite (HA) nanopowder reinforcement. The powder of Co-Cr-Mo
      alloy was mixed with different amounts of HA by ball milling and it was then cold
      pressed and sintered. X-ray diffraction (XRD) and scanning electron microscopy
      (SEM) techniques were used. Microhardness measurement and compressive tests were
      also carried out. Bioactivity behavior was evaluated in simulated body fluid
      (SBF). A significant decrease in modulus elasticity and an increase in
      microhardness of the sintered composites were observed. Apatite formation on the
      surface of the composites showed that it could successfully convert bioinert Co
      Cr-Mo alloy to bioactive type by adding 10, 15, and 20wt.% HA which have lower
      modulus elasticity and higher microhardness. 

PMID- 25579960
TI  - Characteristics of multi-layer coating formed on commercially pure titanium for
      biomedical applications.
AB  - An innovative multi-layer coating comprising a bioactive compound layer
      (consisting of hydroxyapatite and calcium titanate) with an underlying titanium
      oxide layer (in the form of anatase and rutile) has been developed on Grade 4
      quality commercially pure titanium via a single step micro-arc oxidation process.
      Deposition of a multi-layer coating on titanium enhanced the bioactivity, while
      providing antibacterial characteristics as compared its untreated state.
      Furthermore, introduction of silver (4.6wt.%) into the multi-layer coating during
      micro-arc oxidation process imposed superior antibacterial efficiency without
      sacrificing the bioactivity. 

PMID- 25579961
TI  - A review: fabrication of porous polyurethane scaffolds.
AB  - The aim of tissue engineering is the fabrication of three-dimensional scaffolds
      that can be used for the reconstruction and regeneration of damaged or deformed
      tissues and organs. A wide variety of techniques have been developed to create
      either fibrous or porous scaffolds from polymers, metals, composite materials and
      ceramics. However, the most promising materials are biodegradable polymers due to
      their comprehensive mechanical properties, ability to control the rate of
      degradation and similarities to natural tissue structures. Polyurethanes (PUs)
      are attractive candidates for scaffold fabrication, since they are biocompatible,
      and have excellent mechanical properties and mechanical flexibility. PU can be
      applied to various methods of porous scaffold fabrication, among which are
      solvent casting/particulate leaching, thermally induced phase separation, gas
      foaming, emulsion freeze-drying and melt moulding. Scaffold properties obtained
      by these techniques, including pore size, interconnectivity and total porosity,
      all depend on the thermal processing parameters, and the porogen agent and
      solvents used. In this review, various polyurethane systems for scaffolds are
      discussed, as well as methods of fabrication, including the latest developments,
      and their advantages and disadvantages. 

PMID- 25579962
TI  - Enhancement of osteogenesis on micro/nano-topographical carbon fiber-reinforced
      polyetheretherketone-nanohydroxyapatite biocomposite.
AB  - As an FDA-approved implantable material, carbon fiber-reinforced
      polyetheretherketone (CFRPEEK) possesses excellent mechanical properties similar
      to those of human cortical bone and is a prime candidate to replace conventional
      metallic implants. The bioinertness and inferior osteogenic properties of
      CFRPEEK, however, limit its clinical application as orthopedic/dental implants.
      The present work aimed at developing a novel carbon fiber-reinforced
      polyetheretherketone-nanohydroxyapatite (PEEK/CF/n-HA) ternary biocomposite with
      micro/nano-topographical surface for the enhancement of the osteogenesis as a
      potential bioactive material for bone grafting and bone tissue-engineering
      applications. The combined modification of oxygen plasma and sand-blasting could
      improve the hydrophily and generate micro/nano-topographical structures on the
      surface of the CFRPEEK-based ternary biocomposite. The results clearly showcased
      that the micro-/nano-topographical PEEK/n-HA/CF ternary biocomposite demonstrated
      the outstanding ability to promote the proliferation and differentiation of MG-63
      cells in vitro as well as to boost the osseointegration between implant and bone
      in vivo, thereby boding well application to bone tissue engineering. 

PMID- 25579963
TI  - Sugarcane bagasse lignin, and silica gel and magneto-silica as drug vehicles for
      development of innocuous methotrexate drug against rheumatoid arthritis disease
      in albino rats.
AB  - The present study clarifies co-therapy action of deliveries from their textural
      changes point of view. Methotrexate (MTX) was immobilized onto biodegradable
      lignin, silica gel and iron/silica nanocomposite. Loaded-MTX was i.p. injected
      into albino rats at doses of 0.25 and 0.5mg/kg/week for 2.5months, after which
      spleen, liver, testes and knee joint tissues were collected for tests. IFN-gamma
      and IL-17A mRNA gene expressions in spleen in all biological samples were
      determined by RT-PCR. Physicochemical features of drug carriers were monitored by
      XRD, BET-PSD, SEM and TEM. Drug inflammatory-site targeting was found to be
      closely related to the physico-features of deliverers. The interlayered lignin of
      micro- and meso-pore channels directed MTX toward concealed infected cells in
      liver and testes tissues, while meso-structured silica flacks satisfied by
      gathering MTX around knee joints. The magneto-silica nanocomposite targeted MTX
      toward spleen tissue, which is considered as a lively factory for the production
      of electron rich compounds. 

PMID- 25579964
TI  - Design and fabrication of an aptasensor for chloramphenicol based on energy
      transfer of CdTe quantum dots to graphene oxide sheet.
AB  - Detection and quantification of chloramphenicol have played essential roles in
      the effort to minimize food safety risk. Herein, a sophisticated "turn on"
      aptasensor based on aptamer-CdTe quantum dots (Apt-QDs) and graphene oxide (GO)
      was developed for chloramphenicol sensing. In this assay, the fluorescence of
      CdTe QDs-Apt was efficiently quenched through energy transfer from QDs-Apt to GO,
      and chloramphenicol was detected by recovering the quenched fluorescence due to
      specific binding between aptamer and chloramphenicol. The results indicated that
      the addition of a CdTe QDs-labeled aptamer to a GO solution (250MUg/mL) led to a
      high quenching efficiency, yielding over 90% fluorescence quenching. Using a
      series of chloramphenicol concentrations (0.1 to 10nM) aptasensor provides a
      limit of detection and limit of quantification at 98pM and 987pM, respectively.
      Linearity of response over chloramphenicol was demonstrated (r>0.99).
      Furthermore, the GO-based aptasensor exhibited excellent selectivity toward
      chloramphenicol compared to other synthetic drugs with similar structures such as
      thiamphenicol, metronidazole and nitrofurantoin. Good reproducibility and
      precision (RSD 4.73%, n=10) of the assay indicates the ability of the aptasensor
      for routine quantitative trace analysis of chloramphenicol. Our results suggested
      that the prepared aptasensor was also well qualified for the detection of
      chloramphenicol in milk with a limit of detection of 0.2ppb. 

PMID- 25579965
TI  - The influence of electrospun fibre size on Schwann cell behaviour and axonal
      outgrowth.
AB  - Fibrous substrates functioning as temporary extracellular matrices can be
      prepared easily by electrospinning, yielding fibrous matrices suitable as
      internal fillers for nerve guidance channels. In this study, gelatin micro- or
      nano-fibres were prepared by electrospinning by tuning the gelatin concentration
      and solution flow rate. The effect of gelatin fibre diameter on cell adhesion and
      proliferation was tested in vitro using explant cultures of Schwann cells (SC)
      and dorsal root ganglia (DRG). Cell adhesion was assessed by quantifying the cell
      spreading area, actin cytoskeleton organization and focal adhesion complex
      formation. Nano-fibres promoted cell spreading and actin cytoskeleton
      organization, increasing cellular adhesion and the proliferation rate. However,
      both migration rate and motility, quantified by transwell and time lapse assays
      respectively, were greater in cells cultured on micro-fibres. Finally, there was
      more DRG axon outgrowth on micro-fibres. These data suggest that the topography
      of electrospun gelatin fibres can be adjusted to modulate SC and axon
      organization and that both nano- and micro-fibres are promising fillers for the
      design of devices for peripheral nerve repair. 

PMID- 25579966
TI  - Maghemite based silicone composite for arterial embolization hyperthermia.
AB  - Maghemite nanoparticle based silicone composite for application in arterial
      embolization hyperthermia is developed. It possesses embolization ability, high
      heating efficiency in alternating magnetic fields and radiopaque property. The
      initial components of the composite are selected so that the material stays
      liquid for 20min, providing the opportunity for transcatheter transportation and
      filling of the tumour vascular system. After this induction period the viscosity
      increases rapidly and soft embolus is formed which is able to occlude the tumour
      blood vessels. The composite is thermally stable up to 225 degrees C, displays
      rubber-elastic properties and has a thermal expansion coefficient higher than
      that of blood. Maghemite nanoparticles uniformly distributed in the composite
      provide its rapid heating (tens of  degrees Cmin(-1)) due to Neel magnetization
      relaxation. Required X-ray contrast of composite is achieved by addition of
      potassium iodide. 

PMID- 25579967
TI  - The influence of silanisation on the mechanical and degradation behaviour of
      PLGA/HA composites.
AB  - This study investigates the influence of silanisation on the mechanical and
      degradation behaviour of PLGA/HA composites. Three different silanes
      (mercaptopropyl trimethoxy silane (MPTMS), aminopropyl trimethoxy silane (APTMS)
      and aminopropyltriethoxy silane (APTES)) were applied to HA substrates in order
      to study the effect of head group (which binds to the polymer) and tail group
      (which binds to the surface hydroxyl groups in HA). A composite of hydroxyapatite
      (HA) and poly(d,l lactide-co-glycolide (50:50)) (PLGA) was investigated. The
      influence of concentration, the reaction time, drying temperature and substrate
      surface on silanisation was examined. TGA was used to detect the degree of
      silanisation. HA with MPTMS (1wt.% MPTMS with reaction time of 1h) was used as
      filler in PLGA-30wt.% HA composites for an in-vitro degradation study carried out
      in PBS. In addition, the mechanical properties of the composites were studied.
      Silanisation affects the properties of the composite by improving the bonding at
      the interface and hence it was found to influence the plastic mechanical
      properties rather than the elastic mechanical properties or the degradation
      profile of the composite. 

PMID- 25579969
TI  - Dewetting based fabrication of fibrous micro-scaffolds as potential injectable
      cell carriers.
AB  - Although regenerative medicine utilizing tissue scaffolds has made enormous
      strides in recent years, many constraints still hamper their effectiveness. A
      limitation of many scaffolds is that they form surface patches, which are not
      particularly effective for some types of "wounds" that are deep within tissues,
      e.g., stroke and myocardial infarction. In this study, we reported the generation
      of fibrous micro-scaffolds feasible for delivering cells by injection into the
      tissue parenchyma. The micro-scaffolds (widths<100MUm) were made by dewetting of
      poly(lactic-co-glycolic acid) thin films containing parallel strips, and cells
      were seeded to form cell/polymer micro-constructs during or post the micro
      scaffold fabrication process. Five types of cells including rat induced vascular
      progenitor cells were assessed for the formation of the micro-constructs.
      Critical factors in forming fibrous micro-scaffolds via dewetting of polymer thin
      films were found to be properties of polymers and supporting substrates,
      temperature, and proteins in the culture medium. Also, the ability of cells to
      attach to the micro-scaffolds was essential in forming cell/polymer micro
      constructs. Both in vitro and in vivo assessments of injecting these micro
      scaffolding constructs showed, as compared to free cells, enhanced cell retention
      at the injected site, which could lead to improved tissue engineering and
      regeneration. 

PMID- 25579970
TI  - Performance of electrodes synthesized with polyacrylonitrile-based carbon
      nanofibers for application in electrochemical sensors and biosensors.
AB  - The purpose of this work was to investigate the performance of electrodes
      synthesized with Polyacrylonitrile-based carbon nanofibers (PAN-based CNFs). The
      homogenous PAN solutions with different concentrations were prepared and
      electrospun to acquire PAN nanofibers and then CNFs were fabricated by heat
      treatment. The effective parameters for the production of electrospun CNF
      electrode were investigated. Scanning electron microscopy (SEM) was used to
      characterize electrospun nanofibers. Cyclic voltammetry was applied to
      investigate the changes of behavior of electrospun CNF electrodes with different
      diameters. The structure of CNFs was also evaluated via X-ray diffraction (XRD)
      and Raman spectroscopy. The results exhibited that diameter of nanofibers reduced
      with decreasing polymer concentration and applied voltage and increasing tip-to
      collector distance, while feeding rate did not have significant effect on
      nanofiber diameter. The investigations of electrochemical behavior also
      demonstrated that cyclic voltammetric response improved as diameter of CNFs
      electrode decreased. 

PMID- 25579971
TI  - Relatively uniform and accelerated degradation of pure iron coated with micro
      patterned Au disc arrays.
AB  - Pure iron has been proven to be a potential biodegradable metal, but its
      degradation rate was too slow. To accelerate its biodegradation, micro-patterned
      Au disc films were deposited on the surface of pure iron by vacuum sputtering.
      The influence of Au disc films on the degradation of pure iron matrix in vitro
      was investigated in the present study. Electrochemical measurement results
      indicated that the corrosion current density of pure iron coated with micro
      patterned Au disc films in Hank's solution was 4 times larger than that of the
      uncoated one, while the difference between the influences of micro-patterned Au
      discs with different diameters on the corrosion rate of pure iron was
      insignificant. Immersion test indicated that the corrosion depth for pure iron
      coated with Au disc films was about three times as that of bare pure iron. Both
      electrochemical test and immersion test revealed that the corrosion of pure iron
      matrix coated with Au disc array became more uniform. 

PMID- 25579972
TI  - Stearic acid based oleogels: a study on the molecular, thermal and mechanical
      properties.
AB  - Stearic acid and its derivatives have been used as gelators in food and
      pharmaceutical gel formulations. However, the mechanism pertaining to the stearic
      acid based gelation has not been deciphered yet. Keeping that in mind, we
      investigated the role of stearic acid on physic-chemical properties of oleogel.
      For this purpose, two different oil (sesame oil and soy bean oil)
      formulations/oleogels were prepared. In depth analysis of gel kinetics, gel
      microstructure, molecular interactions, thermal and mechanical behaviors of the
      oleogels were done. The properties of the oleogels were dependent on the type of
      the vegetable oil used and the concentration of the stearic acid. Avrami analysis
      of DSC thermograms indicated that heterogeneous nucleation was coupled with the
      one-dimensional growth of gelator fibers as the key phenomenon in the formation
      of oleogels. Viscoelastic and pseudoplastic nature of the oleogels was analyzed
      in-depth by fitting the stress relaxation data in modified Peleg's model and
      rheological studies, respectively. Textural studies have revealed that the
      coexistence of hydrogen bond dissipation and formation of new bonds is possible
      under stress conditions in the physical oleogels. 

PMID- 25579968
TI  - Current wound healing procedures and potential care.
AB  - In this review, we describe current and future potential wound healing treatments
      for acute and chronic wounds. The current wound healing approaches are based on
      autografts, allografts, and cultured epithelial autografts, and wound dressings
      based on biocompatible and biodegradable polymers. The Food and Drug
      Administration approved wound healing dressings based on several polymers
      including collagen, silicon, chitosan, and hyaluronic acid. The new potential
      therapeutic intervention for wound healing includes sustained delivery of growth
      factors, and siRNA delivery, targeting microRNA, and stem cell therapy. In
      addition, environment sensors can also potentially utilize to monitor and manage
      microenvironment at wound site. Sensors use optical, odor, pH, and hydration
      sensors to detect such characteristics as uric acid level, pH, protease level,
      and infection - all in the hopes of early detection of complications. 

PMID- 25579973
TI  - Synthesis of highly fluorescent hydrophobic carbon dots by hot injection method
      using Paraplast as precursor.
AB  - We have reported synthesis of bright blue colored hydrophobic carbon dots (hC
      dots) using highly pure blend of polymers called Paraplast. We developed a hot
      injection method for making nearly monodispersed hC-dots with a diameter in a
      range: 5-30nm as confirmed by high resolution transmission electron microscopy
      (HRTEM). The involvement of various functional groups was confirmed by Fourier
      transform infra-red (FTIR) spectroscopy. These hC-dots were incubated with breast
      cancer stem cells in order to check the entry as well as biological imaging. The
      cells were analyzed using epifluorescent microscopy. hC-dots showed concentration
      dependent cytotoxicity (LD50: 50mg/ml) and could be used for bioimaging even at
      lower concentration (0.5mg/ml). hC-dots were found to be versatile agents for
      peeping inside the cells which could also be used for delivery of water insoluble
      chemotherapeutic agents to variety of solid tumors. 

PMID- 25579974
TI  - Gelatin-GAG electrospun nanofibrous scaffold for skin tissue engineering:
      fabrication and modeling of process parameters.
AB  - Electrospinning is a very useful technique for producing polymeric nanofibers by
      applying electrostatic forces. In this study, fabrication of novel gelatin/GAG
      nanofibrous mats and also the optimization of electrospinning process using
      response surface methodology were reported. At optimization section, gelatin/GAG
      blend ratio, applied voltage and feeding rate, their individual and interaction
      effects on the mean fiber diameter (MFD) and standard deviation of fiber diameter
      (SDF) were investigated. The obtained model for MFD has a quadratic relationship
      with gelatin/GAG blend ratio, applied voltage and feeding rate. The interactions
      of blend ratio and applied voltage and also applied voltage and flow rate were
      found significant but the interactions of blend ratio and flow rate were ignored.
      The optimum condition for gelatin/GAG electrospinning was also introduced using
      the model obtained in this study. The potential use of optimized electrospun mat
      in skin tissue engineering was evaluated using culturing of human dermal
      fibroblast cells (HDF). The SEM micrographs of HDF cells on the nanofibrous
      structure show that fibroblast cells can highly attach, grow and populate on the
      fabricated scaffold surface. The electrospun gelatin/GAG nanofibrous mats have a
      potential for using as scaffold for skin, cartilage and cornea tissue
      engineering. 

PMID- 25579976
TI  - Phosphorylation of cohesin Rec11/SA3 by casein kinase 1 promotes homologous
      recombination by assembling the meiotic chromosome axis.
AB  - In meiosis, cohesin is required for sister chromatid cohesion, as well as meiotic
      chromosome axis assembly and recombination. However, mechanisms underlying the
      multifunctional nature of cohesin remain elusive. Here, we show that fission
      yeast casein kinase 1 (CK1) plays a crucial role in assembling the meiotic
      chromosome axis (so-called linear element: LinE) and promoting recombination. An
      in vitro phosphorylation screening assay identified meiotic cohesin subunit
      Rec11/SA3 as an excellent substrate of CK1. The phosphorylation of Rec11 by CK1
      mediates the interaction with the Rec10/Red1/SCP2 axis component, a key step in
      meiotic chromosome axis assembly, and is dispensable for sister chromatid
      cohesion. Crucially, the expression of Rec11-Rec10 fusion protein nearly
      completely bypasses the requirement for CK1 or cohesin phosphorylation for LinE
      assembly and recombination. This study uncovers a central mechanism of the
      cohesin-dependent assembly of the meiotic chromosome axis and recombination
      apparatus that acts independently of sister chromatid cohesion. 

PMID- 25579977
TI  - Influence of exercise training mode on arterial diameter: A systematic review and
      meta-analysis.
AB  - OBJECTIVES: To examine whether differences in arterial diameter exist between
      athletes participating in endurance, resistance or mixed exercise training.
      DESIGN: A systematic review with meta-analysis. METHODS: Random effects meta
      analyses of the weighted mean difference in aortic, carotid, brachial and femoral
      arterial diameters, height and body mass were conducted on data from 16 peer
      reviewed studies indexed on PubMed, MEDLINE, SCOPUS and Sport Discus. Effect
      sizes were calculated as the standardised difference in means (delta), and used
      to compare endurance (n=163), resistance (n=192), and mixed trained athletes
      (n=360), with controls (n=440). RESULTS: Compared to controls, endurance athletes
      displayed the greatest difference in diameter in the brachial artery (delta=1.84,
      95% CI: 0.59, 3.09, p<0.01), whereas for mixed athletes, the greatest difference
      in diameter occurred in the femoral artery (delta=3.65, 95% CI: 2.21, 5.10,
      p<0.01), despite there being no differences in height or body mass between these
      groups. Resistance athletes had a significantly greater body mass (p=0.047) and
      aortic diameter (delta=1.81, 95% CI: 1.58, 2.05, p<0.01) than controls, however
      differences in other vessels could not be determined through meta-analysis due to
      insufficient data. CONCLUSIONS: Our results provide evidence for localised
      arterial differences, which occur more extensively in peripheral vessels
      (brachial and femoral). Chronically, vascular remodelling may occur as a result
      of the specific haemodynamic conditions within each vessel, which likely differs
      depending on the mode of exercise. In the future, empirical research is needed to
      understand the effect of resistance training on chronic vascular remodelling, as
      this is not well documented.

PMID- 25579975
TI  - Salvador-Warts-Hippo pathway in a developmental checkpoint monitoring helix-loop
      helix proteins.
AB  - The E proteins and Id proteins are, respectively, the positive and negative
      heterodimer partners for the basic-helix-loop-helix protein family and as such
      contribute to a remarkably large number of cell-fate decisions. E proteins and Id
      proteins also function to inhibit or promote cell proliferation and cancer. Using
      a genetic modifier screen in Drosophila, we show that the Id protein
      Extramacrochaetae enables growth by suppressing activation of the Salvador-Warts
      Hippo pathway of tumor suppressors, activation that requires transcriptional
      activation of the expanded gene by the E protein Daughterless. Daughterless
      protein binds to an intronic enhancer in the expanded gene, both activating the
      SWH pathway independently of the transmembrane protein Crumbs and bypassing the
      negative feedback regulation that targets the same expanded enhancer. Thus, the
      Salvador-Warts-Hippo pathway has a cell-autonomous function to prevent
      inappropriate differentiation due to transcription factor imbalance and monitors
      the intrinsic developmental status of progenitor cells, distinct from any
      responses to cell-cell interactions. 

PMID- 25579979
TI  - Inter-joint coordination strategies during unilateral stance 6-months following
      first-time lateral ankle sprain.
AB  - BACKGROUND: Longitudinal analyses of participants with a history of lateral ankle
      sprain are lacking. This investigation combined measures of inter-joint
      coordination and stabilometry to evaluate eyes-open (condition 1) and eyes-closed
      (condition 2) static unilateral stance performance in a group of participants, 6
      months after they sustained an acute, first-time lateral ankle sprain in
      comparison to a control group. METHODS: Sixty-nine participants with a 6-month
      history of first-time lateral ankle sprain and 20 non-injured controls completed
      three 20-second unilateral stance task trials in conditions 1 and 2. An adjusted
      coefficient of multiple determination statistic was used to compare stance limb 3
      dimensional kinematic data for similarity in the aim of establishing patterns of
      lower-limb inter-joint coordination. The fractal dimension of the stance limb
      centre of pressure path was also calculated. FINDINGS: Between-group analyses
      revealed significant differences in stance limb inter-joint coordination
      strategies for conditions 1 and 2, and in the fractal dimension of the centre-of
      pressure path for condition 2 only. Injured participants displayed increases in
      ankle-hip linked coordination compared to controls in condition 1
      (sagittal/frontal plane: 0.15 [0.14] vs 0.06 [0.04]; eta(2)=.19;
      sagittal/transverse plane: 0.14 [0.11] vs 0.09 [0.05]; eta(2)=0.14) and condition
      2 (sagittal/frontal plane: 0.15 [0.12] vs 0.08 [0.06]; eta(2)=0.23), with an
      associated decrease in the fractal dimension of the centre-of-pressure path
      (injured limb: 1.23 [0.13] vs 1.36 [0.13]; eta(2)=0.20). INTERPRETATION:
      Participants with a 6-month history of first-time lateral ankle sprain exhibit a
      hip-dominant coordination strategy for static unilateral stance compared to non
      injured controls.

PMID- 25579980
TI  - The physician and the painter: an inter-professional dialogue.

PMID- 25579978
TI  - The degenerative state of the intervertebral disk independently predicts the
      failure of human lumbar spine to high rate loading: an experimental study.
AB  - BACKGROUND: In the elderly, 30%-50% of patients report a fall event to precede
      the onset of vertebral fractures. The dynamic characteristics of the spine
      determine the peak forces on the vertebrae in a fall. However, we know little
      about the effect of intervertebral disk degeneration on the failure of human
      spines under the high loading rates associated with such falls. We hypothesized
      that MR estimates of disk hydration and viscoelastic properties will provide
      better estimates of failure strength than bone density alone. METHODS: Seventeen
      L1-L3 human spine segments were imaged (magnetic resonance imaging, dual-energy X
      ray absorptiometry), their dynamic responses quantified using pendulum based
      impact, and the spines tested to failure under high rate loading simulating a
      fall event. The spines' stiffness and damping constants were computed (Kelvin
      Voigt model) with disk hydration and geometry assessed from T2 and proton density
      images. FINDINGS: Under impact, the spines exhibited a second-order underdamped
      response with stiffness and damping ranging (17.9-754.5) kN/m and (133.6-905.3)
      Ns/m respectively. Damping, but not stiffness, was negatively correlated with
      higher ultimate strength (P<0.05). Higher bone mineral density and MR-estimated
      disk hydration correlated with higher ultimate strength (P<0.01 for both). No
      such correlations were observed for the T2 values. Adding disk hydration yielded
      a 20% increase in the model's association with failure load compared to bone
      density alone (MANOVA, P<0.001). INTERPRETATION: The strong correlation between
      disk viscoelastic properties and MR-estimated hydration with the spine segments'
      ultimate strength clearly demonstrates the need to include disk degeneration as
      part of fracture risk assessment in the elderly spine.

PMID- 25579981
TI  - Correction of misclassification bias induced by the residential mobility in
      studies examining the link between socioeconomic environment and cancer
      incidence.
AB  - BACKGROUND: Many international ecological studies that examine the link between
      social environment and cancer incidence use a deprivation index based on the
      subjects' address at the time of diagnosis to evaluate socioeconomic status.
      Thus, social past details are ignored, which leads to misclassification bias in
      the estimations. The objectives of this study were to include the latency delay
      in such estimations and to observe the effects. METHODS: We adapted a previous
      methodology to correct estimates of the influence of socioeconomic environment on
      cancer incidence considering the latency delay in measuring socioeconomic status.
      We implemented this method using French data. We evaluated the misclassification
      due to social mobility with census data and corrected the relative risks.
      RESULTS: Inclusion of misclassification affected the values of relative risks,
      and the corrected values showed a greater departure from the value 1 than the
      uncorrected ones. For cancer of lung, colon-rectum, lips-mouth-pharynx, kidney
      and esophagus in men, the over incidence in the deprived categories was augmented
      by the correction. CONCLUSIONS: By not taking into account the latency period in
      measuring socioeconomic status, the burden of cancer associated with social
      inequality may be underestimated.

PMID- 25579982
TI  - "Lupara Bianca" a way to hide cadavers after Mafia homicides. A cemetery of
      Italian Mafia. A case study.
AB  - The Gargano, also known as the 'Spur of Italy', is a sub-region of Italy which is
      located in North of Puglia, in the Province of Foggia. A ravine located in this
      area was used as a dumping ground in past. During a clearing operation, a team of
      speleologists discovered human skeletal remains, which led to an official
      investigation by the local prosecutor's office. The prosecutor called a team of
      forensic specialist for a scene investigation to recover and identify the human
      skeletal remains. Four different human skeletal remains located at four different
      levels of depth underground were found and were in different conditions. A
      complete forensic investigation was initiated and comprised of radiological
      imaging with DNA profiling. Three of the four human skeletal remains that were
      found were identified as those belonging to men who vanished mysteriously in the
      nineties. The studies conducted have demonstrated that the victims found were
      murdered and the murders were attributed to the "Mafia of Gargano". The Mafia of
      Gargano was officially recognized as a criminal organization dating back to 2009
      and their criminal activities included the smuggling of firearms and cigarettes,
      human trafficking, and smuggling of undocumented immigrants. Murders in which
      corpses are made to disappear is common practice in criminal activities including
      that of the Italian Mafia. The "Lupara Bianca" is a colloquial term commonly used
      in Sicily to refer to concealed murders. To the best of our knowledge, this is
      the first reported study describing the discovery of one of the locations used
      extensively by the local Mafia as a "cemetery" for victims of "Lupara Bianca"
      homicides. Based on evidences collected at the site, an explanation of this
      homicidal modality will be provided. 

PMID- 25579983
TI  - Myeloid derived suppressor cell infiltration of murine and human gliomas is
      associated with reduction of tumor infiltrating lymphocytes.
AB  - Myeloid derived suppressor cells (MDSCs) are bone marrow derived cells with
      immunosuppressive properties. We have shown previously that MDSCs numbers are
      elevated in the circulation of GBM patients and that they produce reversible T
      cell dysfunction. Here, we evaluated whether MDSCs infiltrate human GBM tissues,
      and whether a commonly used mouse model of GBM reproduces the biology of MDSCs
      that is observed in patients. We evaluated tumor specimens from patients with
      newly diagnosed GBM. We harvested and evaluated normal brain, tumors and
      hematopoietic tissues from control, vehicle and sunitinib-treated mice. In human
      GBM tumors, MDSCs represented 5.4 +/- 1.8 % of total cells. The majority of MDSCs
      (CD33+HLADR-) were lineage negative (CD14-CD15-), followed by granulocytic
      (CD15+CD14-) and monocytic (CD15-CD14+) subtypes. In murine GBM tumors, MDSCs
      were 8.06 +/- 0.78 % of total cells, of which more were monocytic (M-MDSC, CD11b+
      Gr1-low) than granulocytic (G-MDSC, CD11b+ Gr1-high). Treatment with the tyrosine
      kinase inhibitor sunitinib decreased the infiltration of both granulocytic and
      monocytic MDSCs in murine GBM tumors. In the hematopoietic tissues, circulating G
      MDSC blood levels were reduced after sunitinib treatment. In tumors, both CD3(+)
      and CD4(+) T cell counts increased following sunitinib treatment (p <= 0.001).
      Total T cell proliferation (p < 0.001) and interferon gamma production (p =
      0.004) were increased in the spleens of sunitinib treated mice. Sunitinib-treated
      mice survived longer than vehicle-treated mice (p = 0.002). MDSCs are present in
      both human and mouse GBM tumors. Sunitinib may have an immunostimulatory effect,
      as its use is associated with a reduction in G-MDSCs and improvement in anti
      tumor immune function.

PMID- 25579984
TI  - Predicting the efficacy of an oral paclitaxel formulation (DHP107) through
      modeling and simulation.
AB  - PURPOSE: DHP107 is an oral paclitaxel under development. The present study
      characterized the pharmacokinetic properties of DHP107 and predicted the efficacy
      in comparison to that of intravenous paclitaxel, using modeling and simulation of
      data from the early phase of clinical development. METHODS: In the first-in-human
      study of the pharmacokinetic characteristics of DHP107 and intravenous
      paclitaxel, patients received DHP107 60 to 600 mg/m(2), followed by intravenous
      paclitaxel 175 mg/m(2). Using the pharmacokinetic model of DHP107 from the
      present analysis and from a previously published pharmacodynamic analysis of the
      association between paclitaxel concentration and neutropenia, phase I clinical
      trial for DHP107, with a modified Fibonacci dose escalation scheme, were
      simulated to predict the maximal tolerated dose (MTD). Additional simulations of
      paclitaxel concentration over time were conducted to compare the efficacy of
      DHP107 with that of intravenous paclitaxel, based on time over minimum effective
      concentration. FINDINGS: In the clinical trial simulation, 480 mg/m(2) was the
      most frequently predicted MTD of DHP107. In the simulations for efficacy, the
      times over minimum effective concentration with DHP107 at the predicted MTD were
      greater than those of intravenous paclitaxel in weekly regimens. IMPLICATIONS:
      The findings from this analysis suggest the possibility of efficacy of DHP107 in
      weekly regimens and provides a scientific rationale for further development.
      Based on findings from modeling and simulation, DHP107 was predicted to be more
      efficacious compared with intravenous paclitaxel in weekly regimens, and this
      finding should be confirmed in further clinical trials.

PMID- 25579985
TI  - Surgical management of adult-onset cystic hygroma in the axilla.
AB  - INTRODUCTION: Lymphatic malformations are commonly recognized as relatively
      benign congenital masses affecting infants and children in the perinatal period.
      In children, these masses are most commonly found in the neck, and are
      occasionally seen in other areas of the body. PRESENTATION OF CASE: A 58-year-old
      man presented with an acute axillary swelling measuring approximately 20cm in
      length, 12cm in AP width, and 7cm in depth. Biopsy and cytology analysis
      demonstrated this mass to be a cystic hygroma of adult-onset. DISCUSSION: Given
      its multi-loculated nature and size, it was surgically excised and one year later
      the patient is without evidence of recurrence. CONCLUSION: As the incidence of
      adult-onset cystic hygroma is rare, the nature and reporting of their management
      is limited. This case report contributes to the body of literature which serves
      to elucidate the optimal management of this perinatal condition in adults.

PMID- 25579986
TI  - Surgical management of pulmonary arteriovenous fistula in a female patient.
AB  - INTRODUCTION: We herein describe a rare case of a pulmonary arteriovenous fistula
      (PAVF). PRESENTATION OF CASE: The patient was a 20-year-old asymptomatic female,
      admitted to our hospital because of an abnormal shadow in the right lung field on
      chest X-rays. Chest computed tomography (CT) revealed two nodules with well
      defined margins in the right upper and lower lobes. Contrast-enhanced three
      dimensional CT (3D-CT) revealed two enhanced solitary lung nodules which were
      connected with linear structures suggestive of feeding arteries and drainage
      veins, respectively. Based on these findings, we made a preoperative diagnosis of
      PAVF. We performed partial pulmonary resection of the right upper and lower lobes
      by video-assisted thoracoscopic surgery (VATS). The histopathological findings
      revealed small and medium-sized vascular channels composed of arteries with mild
      and irregularly thickened muscle walls and juxtaposed or seemingly anastomosing
      dilated veins. Based on these findings, a diagnosis of PAVF was confirmed. The
      patient had an uneventful postoperative course. DISCUSSION: A PAVF is often
      associated with various complications, and pregnancy could be a risk factor for
      these complications because of the increase in the shunt fraction. Females with
      known PAVF should be maximally treated prior to becoming pregnant as
      complications of PAVF during pregnancy can have devastating consequences.
      Therefore, we thought that treatment should be recommended in this case in the
      event she might later choose to become pregnant. CONCLUSION: Surgical resection
      using VATS for a limited number of ipsilateral isolated pulmonary arteriovenous
      fistulae is recommended due to its safety, low recurrence and low mortality rate.

PMID- 25579987
TI  - Effects of ellagic acid-rich extract of pomegranates peel on regulation of
      cholesterol metabolism and its molecular mechanism in hamsters.
AB  - The study investigated the effect of pomegranates ellagic acid (PEA) on blood
      cholesterol and investigated its effects on LXR/RXR/PPAR-ABCA1 nuclear receptors
      signaling pathways of cholesterol metabolism on molecular level in hamsters. In
      this experiment, hamsters were randomly divided into two groups: the first group
      (NG, n = 9) was always fed the normal diet, whereas the other group (HFG, n = 45)
      was fed a high fat diet during the first 4 weeks and then fed the normal diet for
      the last 4 weeks. In HFG, which was divided into five groups (n = 9) during the
      last 4 weeks, three groups were treated with PEA at 44 mg per kg bw, 88 mg per kg
      bw and 177 mg per kg bw, one group was treated with simvastatin at 1.77 mg per kg
      bw, and one was given sterile double-distilled water. The data validated that PEA
      dose-dependently decreased plasma total cholesterol and triglyceride level
      accompanied by a greater excretion of fecal bile acid. The result of RT-PCR
      revealed that PEA up-regulated liver X receptor (LXRalpha), peroxisome
      proliferator-activated receptor alpha (PPARalpha), peroxisome proliferator
      activated receptor gamma (PPARgamma) and their downstream gene ATP-binding
      cassette transporter A1 (ABCA1), with no effect on retinoid X receptor
      (RXRalpha). PEA promoted cholesterol removal by enhancing fecal bile acid and up
      regulation of the two pathways, LXR/PPAR-ABCA1. Moreover, PEA was stronger than
      simvastatin in some aspects. 

PMID- 25579989
TI  - Commentary on: de Ree H, et al. "Health risk assessment of exposure to tricresyl
      phosphates (TCPs) in aircraft: a commentary" [Neurotoxicology (2014),
      http://dx.doi.org/10.1016/j.neuro.2014.08.011].

PMID- 25579988
TI  - Growing perovskite into polymers for easy-processable optoelectronic devices.
AB  - Here we conceive an innovative nanocomposite to endow hybrid perovskites with the
      easy processability of polymers, providing a tool to control film quality and
      material crystallinity. We verify that the employed semiconducting polymer,
      poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV), controls the
      self-assembly of CH3NH3PbI3 (MAPbI3) crystalline domains and favors the
      deposition of a very smooth and homogenous layer in one straightforward step.
      This idea offers a new paradigm for the implementation of polymer/perovskite
      nanocomposites towards versatile optoelectronic devices combined with the
      feasibility of mass production. As a proof-of-concept we propose the application
      of such nanocomposite in polymer solar cell architecture, demonstrating a power
      conversion efficiency up to 3%, to date the highest reported for MEH-PPV. On
      purpose designed polymers are expected to suit the nanocomposite properties for
      the integration in diverse optoelectronic devices via facile processing
      condition.

PMID- 25579990
TI  - Long-term implant fixation and stress-shielding in total hip replacement.
AB  - Implant fixation implies a strong and durable mechanical bond between the
      prosthetic component and host skeleton. Assuming the short-term impediments to
      implant fixation are successfully addressed and that longer-term issues such as
      late infection and mechanical failure of the components are avoided, the
      biological response of the host tissue to the presence of the implant is critical
      to long-term success. In particular, maintenance of adequate peri-prosthetic bone
      stock is a key factor. Two major causes of bone loss in the supporting bone are
      adverse bone remodeling in response to debris shed from the implant and stress
      shielding. Here, I review some of the major lessons learned from studying stress
      shielding-induced bone loss. It is well known that stress-shielding can be
      manipulated by altering implant design, but less well appreciated that the
      development of bone anabolic agents may make it possible to reduce the severity
      of stress-shielding and the associated bone loss by augmenting the host skeleton
      through the use of locally or systemically delivered agents. In most cases,
      mechanical, material and biological factors do not act in isolation, emphasizing
      that it is often not possible to optimize all boundary conditions. 

PMID- 25579991
TI  - Tissue-level remodeling simulations of cancellous bone capture effects of in vivo
      loading in a rabbit model.
AB  - The adaptation of cancellous bone to mechanical stimuli occurs throughout normal
      skeletal growth and aging, as well as in response to surgery, disease and device
      implantation. Previously we developed an in vivo cancellous loading model in the
      distal lateral femur of the rabbit. In response to daily in vivo loading for four
      weeks, bone mass increased, trabeculae thickened and the apparent modulus of the
      underlying cancellous bone increased. Here, we simulated our prior in vivo rabbit
      loading experiment using a cell-based tissue remodeling algorithm (Mullender et
      al., 1994) and compared the results to the in vivo experimental data published
      previously. Cancellous bone tissue was added or removed from the surface of
      trabeculae in regions of high and low mechanical stimulus, respectively. To
      examine the effect of material properties on mechanically regulated adaptation,
      we implemented both a homogeneous material model and a model where the relative
      density of tissue was lower for new and surface bone tissue compared to interior
      tissue. The simulations captured the changes in histomorphometric parameters and
      mechanical properties measured in the in vivo experiment illustrating the ability
      of computational simulations to predict the effect of mechanically regulated
      adaptation on cancellous bone histomorphometry and apparent modulus. 

PMID- 25579992
TI  - Understanding how pre-impact posture can affect injury outcome in side impact
      sled tests using a new tool for visualization of cadaver kinematics.
AB  - The effect of posture and subject-specific factors on injury outcome is an active
      field of research in injury biomechanics, in particular in automotive safety
      research where post-mortem human subjects (PMHS) are used as surrogates. Current
      PMHS tests routinely include acquisition of the subjects' geometry and
      kinematics. However, combining these two datasets to better understand the injury
      mechanism is still a challenge. This study investigated the connection between
      pre-impact posture and resulting injuries in six previously published side impact
      sled tests (three with a rigid wall and three with an airbag) by creating three
      dimensional kinematic animations (3DKA) of the tests. The 3DKA allow qualitative
      assessment of parameters related to posture and their possible effect on injury
      outcome. The orientation of the struck scapula and the lateral leaning of the
      torso were identified as potentially significant parameters. The ranges of
      variation in these parameters were quantified and compared to the number of rib
      fractures for each subject: the data suggested a correlation, but there was
      insufficient data for a probabilistic analysis. The 3DKA were published with this
      study and are freely available. 

PMID- 25579993
TI  - Computational analysis of primary implant stability in trabecular bone.
AB  - Secure fixation of fractured osteoporotic bone is a serious clinical challenge
      mainly because the reduced mechanical competence of low-density bone hampers
      proper implant fixation. Recent experimental findings have shown strong evidence
      for a rather complex bone-implant interface contact behavior, with frictional and
      non-linear mechanical properties. Furthermore, the bone microarchitecture is
      highly diverse even within the same anatomical site of a specific individual. Due
      to this intrinsic variability experimental studies that could analyze in detail
      the contributions of screw designs and thread geometry would require a very large
      amount of bone specimens; this hampers finding potential improvements for implant
      fixation. As a complementary approach, computational methods may overcome this
      limitation, since the same specimen can be tested repeatedly in numerous
      configurations and under various loading conditions. Recent advances in imaging
      techniques combined with parallel computing methods have enabled the creation of
      high-resolution finite-element models that are able to represent bone-implant
      systems in great detail. Yet, the predictive power of the mechanical competence
      of bone-implant systems is still limited, both on the apparent level and on the
      local microstructural level. The current strategy in high-resolution FE models to
      model the bone-implant interface, employing fully bonded cube-like elements,
      needs to be reconsidered, refined and validated, such that it mimics more closely
      the actual non-linear mechanical behavior as observed in vitro in order to
      exploit the full potential of numeric models as an effective, complementary
      research method to physical in vitro models. 

PMID- 25579994
TI  - Accounting for uncertainty in DNA sequencing data.
AB  - Science is defined in part by an honest exposition of the uncertainties that
      arise in measurements and propagate through calculations and inferences, so that
      the reliabilities of its conclusions are made apparent. The recent rapid
      development of high-throughput DNA sequencing technologies has dramatically
      increased the number of measurements made at the biochemical and molecular level.
      These data come from many different DNA-sequencing technologies, each with their
      own platform-specific errors and biases, which vary widely. Several statistical
      studies have tried to measure error rates for basic determinations, but there are
      no general schemes to project these uncertainties so as to assess the surety of
      the conclusions drawn about genetic, epigenetic, and more general biological
      questions. We review here the state of uncertainty quantification in DNA
      sequencing applications, describe sources of error, and propose methods that can
      be used for accounting and propagating these errors and their uncertainties
      through subsequent calculations. 

PMID- 25579995
TI  - Developing Adnectins that target SRC co-activator binding to PXR: a structural
      approach toward understanding promiscuity of PXR.
AB  - The human pregnane X receptor (PXR) is a promiscuous nuclear receptor that
      functions as a sensor to a wide variety of xenobiotics and regulates expression
      of several drug metabolizing enzymes and transporters. We have generated
      "Adnectins", derived from 10th fibronectin type III domain ((10)Fn3), that target
      the PXR ligand binding domain (LBD) interactions with the steroid receptor co
      activator-1 (SRC-1) peptide, displacing SRC-1 binding. Adnectins are structurally
      homologous to the immunoglobulin superfamily. Three different co-crystal
      structures of PXR LBD with Adnectin-1 and CCR1 (CC chemokine receptor-1)
      antagonist Compound-1 were determined. This structural information was used to
      modulate PXR affinity for a related CCR1 antagonist compound that entered into
      clinical trials for rheumatoid arthritis. The structures of PXR with Adnectin-1
      reveal specificity of Adnectin-1 in not only targeting the interface of the SRC-1
      interactions but also engaging the same set of residues that are involved in
      binding of SRC-1 to PXR. Substituting SRC-1 with Adnectin-1 does not alter the
      binding conformation of Compound-1 in the ligand binding pocket. The structure
      also reveals the possibility of using Adnectins as crystallization chaperones to
      generate structures of PXR with compounds of interest. 

PMID- 25579996
TI  - Structural basis of dynamic membrane recognition by trans-Golgi network specific
      FAPP proteins.
AB  - Glycosphingolipid metabolism relies on selective recruitment of the pleckstrin
      homology (PH) domains of FAPP proteins to the trans-Golgi network. The mechanism
      involved is unclear but requires recognition of phosphatidylinositol-4-phosphate
      (PI4P) within the Golgi membrane. We investigated the molecular basis of FAPP1-PH
      domain interactions with PI4P bilayers in liposome sedimentation and membrane
      partitioning assays. Our data reveals a mechanism in which FAPP-PH proteins
      preferentially target PI4P-containing liquid disordered membranes, while liquid
      ordered membranes were disfavored. Additionally, NMR spectroscopy was used to
      identify the binding determinants responsible for recognizing trans-Golgi network
      like bicelles including phosphoinositide and neighboring lipid molecules.
      Membrane penetration by the FAPP1-PH domain was mediated by an exposed, conserved
      hydrophobic wedge next to the PI4P recognition site and ringed by a network of
      complementary polar residues and basic charges. Our data illuminates how
      insertion of a structured loop provides selectivity for sensing membrane fluidity
      and targeting to defined membrane zones and organelles. The determinants of this
      membrane sensing process are conserved across the CERT, OSBP and FAPP family.
      Hence, lipid gradients not only result in differential membrane ordering along
      the secretory pathway but also specifically localize diverse proteins through
      recognition of ensembles of lipid ligands in dynamic and deformable bilayers in
      order to promote anterograde trafficking. 

PMID- 25579997
TI  - Erratum to "epigenetic modifications and potential new treatment targets in
      diabetic retinopathy".
AB  - [This corrects the article DOI: 10.1155/2014/789120.]. 

PMID- 25579998
TI  - Deciphering the protective role of spermidine against saline-alkaline stress at
      physiological and proteomic levels in tomato.
AB  - In this research, the protective effect of spermidine (Spd) in mitigating saline
      alkaline stress in tomato (Solanum lycopersicum L.) at physiological and
      proteomic levels were examined. The results showed that saline-alkaline stress
      induced accumulation of H2O2 and O2(-*), and increased the activities of
      antioxidase (SOD, CAT, and POD). Spermidine efficiently alleviated the inhibitory
      role of saline-alkaline on plant growth and inhibited saline-alkaline stress
      induced H2O2 and O2(-*) accumulation. Proteomics investigations of the leaves of
      tomato seedlings, responding to a 75 mM saline-alkaline solution and 0.25 mM Spd,
      were performed. Maps of the proteome of leaf extracts were obtained by two
      dimensional gel electrophoresis. An average of 49, 47 and 34 spots, which
      appeared repeatedly and that significantly altered the relative amounts of
      polypeptides by more than twofold, were detected for seedlings treated with
      saline-alkaline solution (S) compared to normal solution (CK), saline-alkaline
      plus spermidine (MS) compared to CK, or S versus MS, respectively. Thirty-nine of
      these proteins were identified by matrix-assisted laser desorption ionization
      time of flight (MALDI-TOF) mass spectrometry and were classified into five
      functional categories, including energy and metabolism, signal transduction,
      amino acid metabolism, protein metabolism, and stress-defense response.
      Proteomics analysis coupled with bioinformatics indicated that Spd treatment
      helps tomato seedlings combat saline-alkaline stress by modulating the defense
      mechanism of plants and activating cellular detoxification, which protect plants
      from oxidative damage induced by saline-alkaline stress.

PMID- 25579999
TI  - Laparoscopic interval isthmocervical cerclage with cardiac tape in a patient with
      previous cervical amputation.
AB  - STUDY OBJECTIVE: To show the technique of interval laparoscopic isthmocervical
      cerclage using cotton cardiac tape. DESIGN: Case report (Canadian Task Force
      Classification III). SETTING: A private practice hospital in Brasilia, Brazil.
      PATIENT: A 36-year-old female patient with primary infertility for 2 years caused
      by previous amputation of the cervix because of intraepithelial neoplasia. There
      was no other suspected factor for infertility. Before undergoing in vitro
      fertilization, she was referred for interval cerclage because of anticipated
      cervical insufficiency during an eventual pregnancy. The patient's clinical
      history was unremarkable, except for the fact that she had developed secondary
      dysmenorrhea since the amputation, which prompted her to undergo cervical
      dilatation on 2 occasions. During the physical examination, we noted the absence
      of the exocervix, a mobile and normal-sized uterus and adnexa, and no pain.
      Informed consent was obtained from the patient for this case report. The local
      institutional review board considered this report exempt from approval.
      INTERVENTIONS: The procedure was performed according to the technique described
      by Pereira et al. We incised the visceral peritoneum in the anterior cul-de-sac
      and developed the vesicouterine space for complete exposure of the uterine
      isthmus. Then, we incised the posterior leaf of both broad ligaments superiorly
      to the uterosacral ligaments and medially to the ureter and uterine vessels. We
      aimed to identify the bifurcation of the uterine artery and to create a "window"
      between them and the isthmus to place the cerclage tape. For this purpose, we
      used a 5-mm 36-cm blunt tip retractor for gastric banding (ref 30623G; Karl
      Storz, Tuttlingen, Germany) to transfix the broad ligament, anteriorly to
      posteriorly, under direct vision. We tied 2-0 Vicryl (Ethicon, Sommerville, NJ)
      sutures to the tips of 0.3 * 80 cm cotton cardiac tape (reference FAB-46;
      Ethicon) and pulled both edges of the tape through the windows in the broad
      ligament. The final position of the tape was inferior and medial to the main
      ascending branch of the uterine artery, right over the isthmus, and without any
      vessels interposed between them. This is to avoid any possible compression and
      congestion with uterine progressive enlargement as pregnancy proceeds. We then
      made 6 square knots in the anterior cul-de-sac and adjusted the tension-free tape
      firmly enough to give the uterine corpus support during pregnancy evolution.
      Finally, we closed the visceral peritoneum with a 3-0 PDS running suture
      (Ethicon). MEASUREMENTS AND MAIN RESULTS: The surgery lasted 70 minutes, and
      bleeding was minimal. The patient was discharged the following day. She is
      currently undergoing her 18th week of pregnancy resulting from in vitro
      fertilization treatment, and we wait for her obstetric results. CONCLUSION:
      Cotton cardiac tape is feasible for laparoscopic cerclage and can be used as an
      alternative to the commonly used Mersilene tape (Ethicon). Laparoscopy safely
      allows tape placement medial to the uterine vessels. Additional cases are
      necessary to establish the obstetric effectiveness of cotton cardiac tape for
      laparoscopic cerclage.

PMID- 25580000
TI  - Asymptomatic postmenopausal women with a "thickened" endometrium: false negatives
      versus false positives.

PMID- 25580001
TI  - Reply: To PMID 24632398.

PMID- 25580002
TI  - Use of narrowband imaging for the detection of endometriosis.
AB  - STUDY OBJECTIVE: To show a new technique using narrowband imaging for the
      detection of endometriosis. DESIGN: A step-by-step illustration of the difference
      in visualization of endometriosis using a visible light spectrum laparoscope
      compared with a narrowband imaging light source. SETTING: Radical excision of
      endometriosis is considered the best treatment to control the disease extent and
      symptoms of endometriosis. Therefore, it is imperative that all endometriotic
      lesions are recognized and identified in order to thoroughly remove them. A
      narrowband imaging system enhances the visualization of capillary vessels and
      microstructures containing blood hemoglobin on the mucosal surface. It makes use
      of 415- and 540-nm filters that are strongly absorbed by blood hemoglobin. In
      this manner, microvessels, which are not clearly seen by conventional light, are
      enhanced. With the inherent neovascularization noted in endometriosis,
      endometriotic lesions may be more recognizable. Clear vesicular lesions of
      endometriosis are glandular excrescences, which are early signs of recurrent
      inflammation from endometriosis with accompanying angiogenesis. These are more
      pronounced under narrowband imaging. INTERVENTIONS: The use of the visible light
      spectrum contrasted with narrowband imaging that changes the normal color
      contrasts of the endoscopic image in the different areas of the pelvic cavity.
      MEASUREMENTS AND MAIN RESULTS: Narrowband imaging is helpful as an additional
      modality for the identification of endometriosis. In particular, clear vesicular
      lesions of endometriosis, which are not as evident under the visible light
      spectrum, are more pronounced under narrowband imaging. Its strength lies in its
      usefulness in the treatment of patients with endometriosis with symptoms of pain.
      It is especially useful for those with marked symptoms but, on first glance at
      laparoscopy, seems to have minimal disease. Narrowband imaging enhances the
      endometriotic lesions and makes it easier to visualize and identify them, knowing
      that these subtle lesions may well be the cause of the pain. However, its
      usefulness is decreased if performed after the initiation of surgery because of
      the bleeding incurred from dissection, which makes it difficult to distinguish
      between the red blood cells and endometriotic lesions. CONCLUSION: Narrowband
      imaging can be used as an adjunct to improve the detection of endometriosis.

PMID- 25580003
TI  - Impact of newly diagnosed endometrial polyps during controlled ovarian
      hyperstimulation on in vitro fertilization outcomes.
AB  - STUDY OBJECTIVE: To investigate the impact of newly diagnosed endometrial polyps
      during controlled ovarian hyperstimulation (COH) on the outcomes of fresh in
      vitro fertilization (IVF)-embryo transfer (ET) cycles. DESIGN: A retrospective
      cohort study (Canadian Task Force classification II-3). SETTING: An academic
      center. PATIENTS: All patients initiating IVF cycles at the Ronald O. Perelman
      and Claudia Cohen Center for Reproductive Medicine during a 1-year period.
      Patients were stratified into 2 groups based on the presence or absence of newly
      diagnosed endometrial polyps during COH. INTERVENTIONS: IVF with fresh ET.
      MEASUREMENTS AND MAIN RESULTS: Two thousand nine hundred ninety-three patients
      were identified: 60 in the polyp group and 2933 in the nonpolyp group. The
      overall positive pregnancy, clinical pregnancy, spontaneous miscarriage, and live
      birth rates were similar between the groups. The biochemical pregnancy rate was
      18.3% in the polyp group compared with 9.6% in the nonpolyp group (p = .01). This
      represented a 2-fold increased odds of biochemical pregnancy in the polyp group
      (odds ratio = 2.12; 95% confidence interval, 1.09-4.12) compared with the
      nonpolyp group. CONCLUSION: Newly diagnosed endometrial polyps during COH is
      associated with an increased biochemical pregnancy rate but ultimately does not
      adversely impact clinical pregnancy or live birth rates after fresh IVF-ET.

PMID- 25580004
TI  - Comparison of the sensitivity of prepulse inhibition of the startle reflex and
      operant conditioning in an auditory intensity difference limen paradigm.
AB  - Reward-based operant conditioning (OC) procedures and reflex-based prepulse
      inhibition (PPI) procedures are used in mouse psychoacoustics. Therefore it is
      important to know whether both procedures provide comparable results for
      perceptual measurements. Here we evaluate the sensitivity of the C57BL/6N mouse
      in both procedures by testing the same individuals in the same Intensity
      Difference Limen (IDL) task. Level increments of a 10 kHz tone were presented in
      a train of 10 kHz reference tones. Objective analysis based on signal-detection
      theory was applied to compare the results of OC and PPI procedures. In both
      procedures the sensitivity increased with level increment. In agreement with the
      near miss to Weber's law, sensitivity increased with sound level of the reference
      stimuli. The sensitivity observed in the OC procedure was considerably larger
      than the sensitivity in the PPI procedure. Applying a sensitivity of 1.0 as the
      threshold criterion, mean IDLs in the OC procedure were 5.0, 4.0 and 3.5 dB at
      reference levels of 30, 50 and 75 dB SPL respectively. In the PPI procedure, mean
      IDLs of 18.9 and 17.0 dB at reference levels of 50 and 75 dB SPL respectively
      were observed. Due to the low sensitivity, IDLs could not be determined in the
      PPI procedure at a reference level of 30 dB SPL. Possible causes for the low
      sensitivity in the PPI procedure are discussed. These results challenge the idea
      that both procedures can be used as simple substitutes of one another and the
      experimenter must be aware of the limitations of the respective procedure.

PMID- 25580005
TI  - Perineuronal nets in the auditory system.
AB  - Perineuronal nets (PNs) are a unique and complex meshwork of specific
      extracellular matrix molecules that ensheath a subset of neurons in many regions
      of the central nervous system (CNS). PNs appear late in development and are
      supposed to restrict synaptic plasticity and to stabilize functional neuronal
      connections. PNs were further hypothesized to create a charged milieu around the
      neurons and thus, might directly modulate synaptic activity. Although PNs were
      first described more than 120 years ago, their exact functions still remain
      elusive. The purpose of the present review is to propose the nuclei of the
      auditory system, which are highly enriched in PN-wearing neurons, as particularly
      suitable structures to study the functional significance of PNs. We provide a
      detailed description of the distribution of PNs from the cochlear nucleus to the
      auditory cortex considering distinct markers for detection of PNs. We further
      point to the suitability of specific auditory neurons to serve as promising model
      systems to study in detail the contribution of PNs to synaptic physiology and
      also more generally to the functionality of the brain.

PMID- 25580006
TI  - Applicability of optimal functional tuning in density functional calculations of
      ionization potentials and electron affinities of adenine-thymine nucleobase pairs
      and clusters.
AB  - The intrinsic properties of DNA and RNA nucleic acid bases (NABs) such as
      ionization potentials (IPs) and electron affinities (EAs) are crucial to reveal
      various biochemical mechanisms. Successful application of density functional
      theory (DFT) using nonempirically tuned long-range corrected (LC) functionals for
      calculation of vertical ionization potentials (VIPs) and electron affinities
      (VEAs) of various adenine-thymine (AT) nucleobase pairs and clusters is
      demonstrated. We employ a tuning method by applying an asymptotically correct
      exchange-correlation potential adjusted to give frontier orbital energies (
      epsilonHOMO and -epsilonLUMO) representing IPs and EAs and assess the quality of
      prediction which is comparable to high-level EOM-IP-CCSD/CCSD methods. The
      delocalization error calculated using different DFT functionals is quantified by
      calculations using fractional electron numbers. The cooperative effect of H
      bonding and pi-stacking on the IPs of AT clusters, as well as the reactivity
      parameters (global hardness and electrophilicity), is quantitatively
      characterized using the tuned LC functionals. The present work aims at providing
      a reliable and efficient theoretical tool for the prediction of the related
      electron donor and acceptor abilities of the NAB systems. 

PMID- 25580008
TI  - miR-342-3p affects hepatocellular carcinoma cell proliferation via regulating NF
      kappaB pathway.
AB  - Recent research indicates that non-coding microRNAs (miRNAs) help regulate basic
      cellular processes in many types of cancer cells. We hypothesized that
      overexpression of miR-342-3p might affect proliferation of hepatocellular
      carcinoma (HCC) cells. After confirming overexpression of miR-342-3p with qRT
      PCR, MTT assay showed that HCC cell proliferation was significantly inhibited by
      miR-342-3p, and that it significantly decreased BrdU-positive cell proliferation
      by nearly sixfold. Searching for targets using three algorithms we found that miR
      342-3p is related to the NF-kappaB pathway and luciferase assay found that IKK
      gamma, TAB2 and TAB3 are miR-342-3p target genes. Results of western blot on
      extracted nuclear proteins of HepG2 and HCT-116 cells showed that miR-342-3p
      reduced and miR-342-3p-in increased p65 nuclear levels and qRT-PCR found that NF
      kappaB pathway downstream genes were downregulated by miR-342-3p and upregulated
      by miR-342-3p-in, confirming that miR-342 targets NF-kappaB pathway.
      Overexpression of Ikk-gamma, TAB2 and TAB3 partially rescued HCC cells
      proliferation inhibited by miR-342-3p. Using the GSE54751 database we evaluated
      expression from 10 HCC samples, which strongly suggested downregulation of miR
      342-3p and we also found inverse expression between miR-342-3p and its targets
      IKK-gamma, TAB2 and TAB3 from 71 HCC samples. Our results show that miR-342-3p
      has a significant role in HCC cell proliferation and is suitable for
      investigation of therapeutic targets. 

PMID- 25580009
TI  - Modeled microgravity suppressed invasion and migration of human glioblastoma U87
      cells through downregulating store-operated calcium entry.
AB  - Glioblastoma is the most common brain tumor and is characterized with robust
      invasion and migration potential resulting in poor prognosis. Previous
      investigations have demonstrated that modeled microgravity (MMG) could decline
      the cell proliferation and attenuate the metastasis potential in several cell
      lines. In this study, we studied the effects of MMG on the invasion and migration
      potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG
      stimulation significantly attenuated the invasion and migration potentials,
      decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and
      downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB
      or stromal interaction molecule 1 (STIM1) downregulation both mimicked the
      effects of MMG on the invasion and migration potentials in U87 cells.
      Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on
      the invasion and migration potentials in U87 cells. Therefore, these findings
      indicated that MMG stimulation inhibited the invasion and migration potentials of
      U87 cells by downregulating the expression of Orai1 and sequentially decreasing
      the SOCE, suggesting that MMG might be a new potential therapeutic strategy in
      glioblastoma treatment in the future. 

PMID- 25580010
TI  - Construction of nerve guide conduits from cellulose/soy protein composite
      membranes combined with Schwann cells and pyrroloquinoline quinone for the repair
      of peripheral nerve defect.
AB  - Regeneration and functional reconstruction of peripheral nerve defects remained a
      significant clinical challenge. Nerve guide conduits, with seed cells or
      neurotrophic factors (NTFs), had been widely used to improve the repair and
      regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an
      antioxidant that can stimulate nerve growth factors (NGFs) synthesis and
      accelerate the Schwann cells (SCs) proliferation and growth. In present study,
      three kinds of nerve guide conduits were constructed: one from cellulose/SPI
      hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one
      from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to
      bridge and repair the sciatic nerve defect in rats, using autograft as control.
      Effects of different nerve guide conduits on the nerve regeneration were
      comparatively evaluated by general analysis, sciatic function index (SFI) and
      histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were
      observed and running through the transparent nerve guide conduits 12 weeks after
      surgery. SFI results indicated that the reconstruction of motor function in CSSPC
      group was better than that in CSSC and CSC groups. HE images from the cross
      sections and longitudinal-sections of the harvested regenerative nerve indicated
      that regenerative nerve fibers had been formed and accompanied with new blood
      vessels and matrix materials in the conduits. TEM images also showed that lots of
      fresh myelinated and non-myelinated nerve fibers had been formed. Parts of
      vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the
      vacuolization and swell of axons was the least serious in CSSPC group. These
      results indicated that CSSPC group had the most ability to repair and reconstruct
      the nerve structure and functions due to the comprehensive contributions from
      hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for
      the applications as nerve guide conduits in the field of nerve tissue
      engineering.

PMID- 25580011
TI  - Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the
      immunosuppressant FK506 and membrane trafficking in fission yeast.
AB  - Cytokinesis is a highly ordered process that divides one cell into two cells,
      which is functionally linked to the dynamic remodeling of the plasma membrane
      coordinately with various events such as membrane trafficking. Calcineurin is a
      highly conserved serine/threonine protein phosphatase, which regulates multiple
      biological functions, such as membrane trafficking and cytokinesis. Here, we
      isolated imp2-c3, a mutant allele of the imp2(+) gene, encoding a homolog of the
      mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using
      a genetic screen for mutations that are synthetically lethal with calcineurin
      deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis
      with multi-septated phenotypes, which was further enhanced upon treatment with
      the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the
      imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and
      putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in
      addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced
      secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant
      cells exhibited a weakened cell wall, similar to the membrane trafficking mutants
      identified in the same genetic screen such as ypt3-i5. These findings implicate
      the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various
      cellular processes, including cytokinesis and cell integrity.

PMID- 25580012
TI  - Facile construction of well-defined fullerene-dendrimer supramolecular
      nanocomposites for bioapplications.
AB  - Well-defined fullerene-dendrimer supramolecular nanocomposites exhibiting uniform
      size, controlled morphology, high fullerene inclusion efficiency, excellent water
      solubility, and non-toxicity were facilely fabricated through complexation of
      carboxyfullerenes with poly(ethylene glycol)-modified poly(amidoamine)
      dendrimers. 

PMID- 25580013
TI  - Chewing and spitting: a marker of psychopathology and behavioral severity in
      inpatients with an eating disorder.
AB  - Chewing and spitting out food is a frequent behavior in hospitalized patients
      with eating disorders (ED). Personality characteristics of those who frequently
      chew-spit (CHSP), the amount of food consumed during CHSP episodes, associated
      sense of loss of control overeating (LOC), and clinical response to hospital
      based treatment have not been examined and were the focus of this study.
      Participants (N=324) were inpatients on a behavioral ED specialty unit. A third
      of the sample (n=107) reported engaging in CHSP in the 8weeks prior to admission
      with 21% (n=69) reporting CHSP at least once per week. Those who engaged in the
      behavior at least weekly (CHSP+) were compared to those with less frequent or no
      CHSP (CHSP-) on demographic and clinical indices and on the EDI, BDI, and the NEO
      FFI. Participants were also asked if their CHSP behavior involved a binge-like
      amount of food (>=1000kcal) or was associated with LOC. The CHSP+ group was more
      likely to have purging diagnoses. After controlling for purging diagnosis, CHSP+
      were found to engage in more restricting, diet pill and laxative use, and
      excessive exercise, and endorsed greater drive for thinness, body
      dissatisfaction, depression, and neuroticism than CHSP-. Among all CHSP+
      participants, LOC was present in 70% and a minority (n=10, 18%) endorsed recent
      CHSP on binge-like amounts of food. This behavior should be assessed routinely in
      all patients, as it appears associated with increased eating behavior severity
      and increased psychiatric comorbidity at hospital admission. 

PMID- 25580014
TI  - Development and application of efficient pathway enumeration algorithms for
      metabolic engineering applications.
AB  - Metabolic Engineering (ME) aims to design microbial cell factories towards the
      production of valuable compounds. In this endeavor, one important task relates to
      the search for the most suitable heterologous pathway(s) to add to the selected
      host. Different algorithms have been developed in the past towards this goal,
      following distinct approaches spanning constraint-based modeling, graph-based
      methods and knowledge-based systems based on chemical rules. While some of these
      methods search for pathways optimizing specific objective functions, here the
      focus will be on methods that address the enumeration of pathways that are able
      to convert a set of source compounds into desired targets and their posterior
      evaluation according to different criteria. Two pathway enumeration algorithms
      based on (hyper)graph-based representations are selected as the most promising
      ones and are analyzed in more detail: the Solution Structure Generation and the
      Find Path algorithms. Their capabilities and limitations are evaluated when
      designing novel heterologous pathways, by applying these methods on three case
      studies of synthetic ME related to the production of non-native compounds in E.
      coli and S. cerevisiae: 1-butanol, curcumin and vanillin. Some targeted
      improvements are implemented, extending both methods to address limitations
      identified that impair their scalability, improving their ability to extract
      potential pathways over large-scale databases. In all case-studies, the
      algorithms were able to find already described pathways for the production of the
      target compounds, but also alternative pathways that can represent novel ME
      solutions after further evaluation. 

PMID- 25580015
TI  - Analytical theory of oxygen transport in the human placenta.
AB  - We propose an analytical approach to solving the diffusion-convection equations
      governing oxygen transport in the human placenta. We show that only two
      geometrical characteristics of a placental cross-section, villi density and the
      effective villi radius, are needed to predict fetal oxygen uptake. We also
      identify two combinations of physiological parameters that determine oxygen
      uptake in a given placenta: (i) the maximal oxygen inflow of a placentone if
      there were no tissue blocking the flow and (ii) the ratio of transit time of
      maternal blood through the intervillous space to oxygen extraction time. We
      derive analytical formulas for fast and simple calculation of oxygen uptake and
      provide two diagrams of efficiency of oxygen transport in an arbitrary placental
      cross-section. We finally show that artificial perfusion experiments with no
      hemoglobin blood tend to give a two-orders-of-magnitude underestimation of the in
      vivo oxygen uptake and that the optimal geometry for such setup alters
      significantly. The theory allows one to adjust the results of artificial placenta
      perfusion experiments to account for oxygen-hemoglobin dissociation. Combined
      with image analysis techniques, the presented model can give an easy-to-use tool
      for prediction of the human placenta efficiency. 

PMID- 25580017
TI  - Egalitarian despots: hierarchy steepness, reciprocity and the grooming-trade
      model in wild chimpanzees, Pan troglodytes.
AB  - Biological market theory models the action of natural selection as a marketplace
      in which animals are viewed as traders with commodities to offer and exchange.
      Studies of female Old World monkeys have suggested that grooming might be
      employed as a commodity to be reciprocated or traded for alternative services,
      yet previous tests of this grooming-trade model in wild adult male chimpanzees
      have yielded mixed results. Here we provide the strongest test of the model to
      date for male chimpanzees: we use data drawn from two social groups (communities)
      of chimpanzees from different populations and give explicit consideration to
      variation in dominance hierarchy steepness, as such variation results in
      differing conditions for biological markets. First, analysis of data from
      published accounts of other chimpanzee communities, together with our own data,
      showed that hierarchy steepness varied considerably within and across communities
      and that the number of adult males in a community aged 20-30 years predicted
      hierarchy steepness. The two communities in which we tested predictions of the
      grooming-trade model lay at opposite extremes of this distribution. Second, in
      accord with the grooming-trade model, we found evidence that male chimpanzees
      trade grooming for agonistic support where hierarchies are steep (despotic) and
      consequent effective support is a rank-related commodity, but not where
      hierarchies are shallow (egalitarian). However, we also found that grooming was
      reciprocated regardless of hierarchy steepness. Our findings also hint at the
      possibility of agonistic competition, or at least exclusion, in relation to
      grooming opportunities compromising the free market envisioned by biological
      market theory. Our results build on previous findings across chimpanzee
      communities to emphasize the importance of reciprocal grooming exchanges among
      adult male chimpanzees, which can be understood in a biological markets framework
      if grooming by or with particular individuals is a valuable commodity.

PMID- 25580018
TI  - Menstruation and School Absenteeism: Evidence from Rural Malawi.
AB  - The provision of toilets and menstrual supplies has emerged as a promising
      programmatic strategy to support adolescent girls' school attendance and
      performance in less developed countries. We use the first round of the Malawi
      Schooling and Adolescent Survey (MSAS) to examine the individual- and school
      level factors associated with menstruation-related school absenteeism. The MSAS
      is a school-based longitudinal survey of adolescent students enrolled in coed
      public primary schools in the southern districts of Machinga and Balaka who were
      aged 14-16 in 2007. Although one-third of female students report missing at least
      one day of school at their last menstrual period, our data suggest that
      menstruation only accounts for a small proportion of all female absenteeism and
      does not create a gender gap in absenteeism. We find no evidence for school-level
      variance in menstruation-related absenteeism, suggesting that absenteeism is not
      sensitive to school environments. Rather, co-residence with a grandmother and
      spending time on school work at home reduce the odds of absence during the last
      menstrual period.

PMID- 25580019
TI  - NVR-BIP: Nuclear Vector Replacement using Binary Integer Programming for NMR
      Structure-Based Assignments.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is an important experimental
      technique that allows one to study protein structure and dynamics in solution. An
      important bottleneck in NMR protein structure determination is the assignment of
      NMR peaks to the corresponding nuclei. Structure-based assignment (SBA) aims to
      solve this problem with the help of a template protein which is homologous to the
      target and has applications in the study of structure-activity relationship,
      protein-protein and protein-ligand interactions. We formulate SBA as a linear
      assignment problem with additional nuclear overhauser effect constraints, which
      can be solved within nuclear vector replacement's (NVR) framework (Langmead, C.,
      Yan, A., Lilien, R., Wang, L. and Donald, B. (2003) A Polynomial-Time Nuclear
      Vector Replacement Algorithm for Automated NMR Resonance Assignments. Proc. the
      7th Annual Int. Conf. Research in Computational Molecular Biology (RECOMB),
      Berlin, Germany, April 10-13, pp. 176-187. ACM Press, New York, NY. J. Comp.
      Bio., (2004), 11, pp. 277-298; Langmead, C. and Donald, B. (2004) An
      expectation/maximization nuclear vector replacement algorithm for automated NMR
      resonance assignments. J. Biomol. NMR, 29, 111-138). Our approach uses NVR's
      scoring function and data types and also gives the option of using CH and NH
      residual dipolar coupling (RDCs), instead of NH RDCs which NVR requires. We test
      our technique on NVR's data set as well as on four new proteins. Our results are
      comparable to NVR's assignment accuracy on NVR's test set, but higher on novel
      proteins. Our approach allows partial assignments. It is also complete and can
      return the optimum as well as near-optimum assignments. Furthermore, it allows us
      to analyze the information content of each data type and is easily extendable to
      accept new forms of input data, such as additional RDCs.

PMID- 25580020
TI  - Does Prison-Based Adult Basic Education Improve Postrelease Outcomes for Male
      Prisoners in Florida?
AB  - The authors use administrative data from Florida to determine the extent to which
      prison-based adult basic education (ABE) improves inmate's postrelease labor
      market outcomes, such as earnings and employment. Using two nonexperimental
      comparison groups, the authors find evidence that ABE participation is associated
      with higher postrelease earnings and employment rates, especially for minorities.
      The authors find that the relationship is the largest for ABE participants who
      had uninterrupted ABE instruction and for those who received other education
      services. However, the results do not find any positive effects of ABE
      participation on reducing recidivism.

PMID- 25580021
TI  - Robust nonlinear regression in applications.
AB  - Robust statistical methods, such as M-estimators, are needed for nonlinear
      regression models because of the presence of outliers/influential observations
      and heteroscedasticity. Outliers and influential observations are commonly
      observed in many applications, especially in toxicology and agricultural
      experiments. For example, dose response studies, which are routinely conducted in
      toxicology and agriculture, sometimes result in potential outliers, especially in
      the high dose groups. This is because response to high doses often varies among
      experimental units (e.g., animals). Consequently, this may result in outliers
      (i.e., very low values) in that group. Unlike the linear models, in nonlinear
      models the outliers not only impact the point estimates of the model parameters
      but can also severely impact the estimate of the information matrix. Note that,
      the information matrix in a nonlinear model is a function of the model
      parameters. This is not the case in linear models. In addition to outliers,
      heteroscedasticity is a major concern when dealing with nonlinear models.
      Ignoring heteroscedasticity may lead to inaccurate coverage probabilities and
      Type I error rates. Robustness to outliers/influential observations and to
      heteroscedasticity is even more important when dealing with thousands of
      nonlinear regression models in quantitative high throughput screening assays.
      Recently, these issues have been studied very extensively in the literature
      (references are provided in this paper), where the proposed estimator is robust
      to outliers/influential observations as well as to heteroscedasticity. The focus
      of this paper is to provide the theoretical underpinnings of robust procedures
      developed recently.

PMID- 25580022
TI  - Distorting Genetic Research about Cancer: From Bench Science to Press Release to
      Published News.
AB  - This study considered genetic research relating to cancer outcomes and behaviors,
      specifically investigating the extent to which claims made in press releases
      (N=23) and mainstream print media (N=71) were fairly derived from their original
      presentation in scholarly journals (N=20). Central claims expressing gene-outcome
      relationships were evaluated by a large pool (N=40) of genetics graduate
      students. Raters judged press release claims as significantly more representative
      of material within the original science journal article compared with news
      article claims. Claims originating in news articles which demonstrated contact
      with individuals not directly involved in the research were judged by experts to
      be more representative of the original science as compared with those that
      demonstrated contact with individuals directly involved in the research.

PMID- 25580023
TI  - Site specific nematode management-development and success in cotton production in
      the United States.
AB  - Variability in edaphic factors such as clay content, organic matter, and nutrient
      availability within individual fields is a major obstacle confronting cotton
      producers. Adaptation of geospatial technologies such global positioning systems
      (GPS), yield monitors, autosteering, and the automated on-and-off technology
      required for site-specific nematicide application has provided growers with
      additional tools for managing nematodes. Multiple trials in several states were
      conducted to evaluate this technology in cotton. In a field infested with
      Meloidogyne spp., both shallow (0 to 0.3 m) and deep (0 to 0.91 m) apparent
      electrical conductivity (ECa) readings were highly correlated with sand content.
      Populations of Meloidogyne spp. were present when shallow and deep EC values were
      less than 30 and 90 mS/m, respectively. Across three years of trials in
      production fields in which verification strips (adjacent nematicide treated and
      untreated rows across all soil zones) were established to evaluate crop response
      to nematicide application, deep EC values from 27.4-m wide transects of
      verification strips were more predictive of yield response to application of 1,3
      dichloropropene than were shallow EC values in one location and both ECa values
      equally effective at predicting responses at the second location. In 2006, yields
      from entire verification strips across three soil zones in four production fields
      showed that nematicide response was greatest in areas with the lowest EC values
      indicating highest content of sand. In 2008 in Ashley and Mississippi Counties,
      AR, nematicide treatment by soil zone resulted in 36% and 42% reductions in the
      amount of nematicide applied relative to whole-field application. In 2007 in
      Bamberg County, SC, there was a strong positive correlation between increasing
      population densities of Meloidogyne incognita and increasing sand content. Trials
      conducted during 2007 and 2009 in South Carolina against Hoplolaimus columbus
      showed a stepwise response to increasing rates of aldicarb in zone 1 but not in
      zones 2 and 3. Site-specific application of nematicides has been shown to be a
      viable option for producers as a potential management tool against several
      nematode pathogens of cotton. 

PMID- 25580024
TI  - Spatial Distribution of Plant-Parasitic Nematodes in Semi-Arid Vitis vinifera
      Vineyards in Washington.
AB  - The most commonly encountered plant-parasitic nematodes in eastern Washington
      Vitis vinifera vineyards are Meloidogyne hapla, Mesocriconema xenoplax,
      Pratylenchus spp., Xiphinema americanum, and Paratylenchus sp.; however, little
      is known about their distribution in the soil profile. The vertical and
      horizontal spatial distribution of plant-parasitic nematodes was determined in
      two Washington V. vinifera vineyards. Others variables measured in these
      vineyards included soil moisture content, fine root biomass, and root
      colonization by arbuscular mycorhizal fungi (AMF). Meloidogyne hapla and M.
      xenoplax were aggregated under irrigation emitters within the vine row and
      decreased with soil depth. Conversely, Pratylenchus spp. populations were
      primarily concentrated in vineyard alleyways and decreased with depth.
      Paratylenchus sp. and X. americanum were randomly distributed within the
      vineyards. Soil water content played a dominant role in the distribution of fine
      roots and plant-parasitic nematodes. Colonization of fine roots by AMF decreased
      directly under irrigation emitters; in addition, galled roots had lower levels of
      AMF colonization compared with healthy roots. These findings will help facilitate
      sampling and management decisions for plant-parasitic nematodes in Washington
      semi-arid vineyards. 

PMID- 25580025
TI  - Effects of a Commercial Formulation of Bacillus firmus I-1582 on Golf Course
      Bermudagrass Infested with Belonolaimus longicaudatus.
AB  - One of the primary pests of bermudagrass (Cynodon spp.) on golf courses in the
      southeastern United States is Belonolaimus longicaudatus (sting nematode). In
      2011, a commercial formulation of Bacillus firmus I-1582, Nortica 5WG, was
      launched in the United States for management of plant-parasitic nematodes on
      turfgrasses. To test the efficacy of late winter/early spring application of this
      biopesticide on B. longicaudatus, two field trials in 2009 compared B. firmus
      with fenamiphos and untreated control treatments. In 2011, two additional field
      trials compared treatment with B. firmus with untreated control only. These
      trials measured treatment effects on the population density of B. longicaudatus,
      turf root length, and turf percent green cover. In all four trials, treatment
      with B. firmus improved root length and decreased numbers of B. longicaudatus in
      contrast to the untreated. These results indicate that late winter/early spring
      application of B. firmus is an effective biopesticide treatment for management of
      B. longicaudatus on golf course bermudagrass. 

PMID- 25580026
TI  - Characterization of Biocontrol Traits in Heterorhabditis floridensis: A Species
      with Broad Temperature Tolerance.
AB  - Biological characteristics of two strains of the entomopathogenic nematode,
      Heterorhabditis floridensis (332 isolated in Florida and K22 isolated in Georgia)
      were described. The identity of the nematode's symbiotic bacteria was elucidated
      and found to be Photorhabdus luminescens subsp. luminescens. Beneficial traits
      pertinent to biocontrol (environmental tolerance and virulence) were
      characterized. The range of temperature tolerance in the H. floridensis strains
      was broad and showed a high level of heat tolerance. The H. floridensis strains
      caused higher mortality or infection in G. mellonella at 30 degrees C and 35
      degrees C compared with S. riobrave (355), a strain widely known to be heat
      tolerant, and the H. floridensis strains were also capable of infecting at 17
      degrees C whereas S. riobrave (355) was not. However, at higher temperatures (37
      degrees C and 39 degrees C), though H. floridensis readily infected G.
      mellonella, S. riobrave strains caused higher levels of mortality. Desiccation
      tolerance in H. floridensis was similar to Heterorhabditis indica (Hom1) and S.
      riobrave (355) and superior to S. feltiae (SN). H. bacteriophora (Oswego) and S.
      carpocapsae (All) exhibited higher desiccation tolerance than the H. floridensis
      strains. The virulence of H. floridensis to four insect pests (Aethina tumida,
      Conotrachelus nenuphar, Diaprepes abbreviatus, and Tenebrio molitor) was
      determined relative to seven other nematodes: H. bacteriophora (Oswego), H.
      indica (Hom1), S. carpocapsae (All), S. feltiae (SN), S. glaseri (4-8 and Vs
      strains), and S. riobrave (355). Virulence to A. tumida was similar among the H.
      floridensis strains and other nematodes except S. glaseri (Vs), S. feltiae, and
      S. riobrave failed to cause higher mortality than the control. Only H.
      bacteriophora, H. indica, S. feltiae, S. riobrave, and S. glaseri (4-8) caused
      higher mortality than the control in C. nenuphar. All nematodes were pathogenic
      to D. abbreviatus though S. glaseri (4-8) and S. riobrave (355) were the most
      virulent. S. carpocapsae was the most virulent to T. molitor. In summary, the H.
      floridensis strains possess a wide niche breadth in temperature tolerance and
      have virulence and desiccation levels that are similar to a number of other
      entomopathogenic nematodes. The strains may be useful for biocontrol purposes in
      environments where temperature extremes occur within short durations. 

PMID- 25580027
TI  - Response of Resistant and Susceptible Bell Pepper (Capsicum annuum) to a Southern
      California Meloidogyne incognita Population from a Commercial Bell Pepper Field.
AB  - To determine the presence and level of root-knot nematode (Meloidogyne spp.)
      infestation in Southern California bell pepper (Capsicum annuum) fields, soil and
      root samples were collected in April and May 2012 and analyzed for the presence
      of root-knot nematodes. The earlier samples were virtually free of root-knot
      nematodes, but the later samples all contained, sometimes very high numbers, of
      root-knot nematodes. Nematodes were all identified as M. incognita. A nematode
      population from one of these fields was multiplied in a greenhouse and used as
      inoculum for two repeated pot experiments with three susceptible and two
      resistant bell pepper varieties. Fruit yields of the resistant peppers were not
      affected by the nematodes, whereas yields of two of the three susceptible pepper
      cultivars decreased as a result of nematode inoculation. Nematode-induced root
      galling and nematode multiplication was low but different between the two
      resistant cultivars. Root galling and nematode reproduction was much higher on
      the three susceptible cultivars. One of these susceptible cultivars exhibited
      tolerance, as yields were not affected by the nematodes, but nematode
      multiplication was high. It is concluded that M. incognita is common in Southern
      California bell pepper production, and that resistant cultivars may provide a
      useful tool in a nonchemical management strategy. 

PMID- 25580028
TI  - Physiological Effects of Meloidogyne incognita Infection on Cotton Genotypes with
      Differing Levels of Resistance in the Greenhouse.
AB  - Greenhouse tests were conducted to evaluate (i) the effect of Meloidogyne
      incognita infection in cotton on plant growth and physiology including the height
      to-node ratio, chlorophyll content, dark-adapted quantum yield of photosystem II,
      and leaf area; and (ii) the extent to which moderate or high levels of resistance
      to M. incognita influenced these effects. Cultivars FiberMax 960 BR (susceptible
      to M. incognita) and Stoneville 5599 BR (moderately resistant) were tested
      together in three trials, and PD94042 (germplasm, susceptible) and 120R1B1
      (breeding line genetically similar to PD94042, but highly resistant) were paired
      in two additional trials. Inoculation with M. incognita generally resulted in
      increases in root gall ratings and egg counts per gram of root compared with the
      noninoculated control, as well as reductions in plant dry weight, root weight,
      leaf area, boll number, and boll dry weight, thereby confirming that growth of
      our greenhouse-grown plants was reduced in the same ways that would be expected
      in field-grown plants. In all trials, M. incognita caused reductions in height-to
      node ratios. Nematode infection consistently reduced the area under the height-to
      node ratio curves for all genotypes, and these reductions were similar for
      resistant and susceptible genotypes (no significant genotype * inoculation
      interaction). Our study is the first to show that infection by M. incognita is
      associated with reduced chlorophyll content in cotton leaves, and the reduction
      in the resistant genotypes was similar to that in the susceptible genotypes (no
      interaction). The susceptible PD94042 tended to have increased leaf temperature
      compared with the genetically similar but highly resistant 120R1B1 (P < 0.08),
      likely attributable to increased water stress associated with M. incognita
      infection. 

PMID- 25580029
TI  - Expression of Phenylalanine Ammonia Lyase Genes in Maize Lines Differing in
      Susceptibility to Meloidogyne incognita.
AB  - Maize is a well-known host for Meloidogyne incognita, and there is substantial
      variation in host status among maize genotypes. In previous work it was observed
      that nematode reproduction increased in the moderately susceptible maize inbred
      line B73 when the ZmLOX3 gene from oxylipid metabolism was knocked out.
      Additionally, in this mutant line, use of a nonspecific primer for phenyl alanine
      ammonialyase (PAL) genes indicated that expression of these genes was reduced in
      the mutant maize plants whereas expression of several other defense related genes
      was increased. In this study, we used more specific gene primers to examine the
      expression of six PAL genes in three maize genotypes that were good, moderate,
      and poor hosts for M. incognita, respectively. Of the six PAL genes interrogated,
      two (ZmPAL3 and ZmPAL6) were not expressed in either M. incognita-infected or
      noninfected roots. Three genes (ZmPAL1, ZmPAL2, and ZmPAL5) were strongly
      expressed in all three maize lines, in both nematode-infected and noninfected
      roots, between 2 and 16 d after inoculation (DAI). In contrast, ZmPAL4 was most
      strongly expressed in the most-resistant maize line W438, was not detected in the
      most-susceptible maize line CML, and was detected only at 8 DAI in the maize line
      B73 that supported intermediate levels of reproduction by M. incognita. These
      observations are consistent with at least one PAL gene playing a role in
      modulating host status of maize toward M. incognita and suggest a need for
      additional research to further elucidate this association. 

PMID- 25580030
TI  - Nematicides enhance growth and yield of rotylenchulus reniformis resistant cotton
      genotypes.
AB  - Rotylenchulus reniformis resistant LONREN-1*FM966 breeding lines developed at
      Auburn University have demonstrated that the nematode resistance is accompanied
      by severe stunting, limited growth, and low yields. The objectives of this study
      were to evaluate the effects of applying nematicides to selected LONREN breeding
      lines on R. reniformis nematode populations, plant stunting, and yield. Four
      resistant breeding lines from the LONREN-1*FM966 cross, one susceptible line from
      the LONREN-1*FM966 cross, as well as LONREN-1, BARBREN-713, and the susceptible
      cultivar DP393 were evaluated with and without nematicides in the presence of R.
      reniformis. In the greenhouse, nematicides increased plant height across all
      genotypes compared with no nematicide. Rotylenchulus reniformis populations were
      50% lower in the resistant lines compared with the susceptible lines at 45 days
      after planting (DAP). In microplot and field trials, the phenotypic stunting of
      all genotypes was reduced by aldicarb with increases in plant heights at 30 and
      75 DAP. Increases in yields were evident across all genotypes treated with
      aldicarb. In all three trial environments, BARBREN-713 outperformed the LONREN
      derived lines as well as 'DP393' in seed cotton yields, while having
      significantly lower R. reniformis egg densities than the susceptible genotypes. 

PMID- 25580031
TI  - Occurrence of Ditylenchus weischeri and Not D. dipsaci in Field Pea Harvest
      Samples and Cirsium arvense in the Canadian Prairies.
AB  - The stem nematode, a parasite of the herbaceous perennial weed, Cirsium arvense
      (L.) Scop. and identified as Ditylenchus dipsaci (Kuhn) Filipjev, was reported in
      the Canadian prairies in 1979. Recently, D. weischeri Chizhov parasitizing
      Cirsium arvense was described in Russia, and it has been shown that this species
      is not an agricultural pest. In this study, we examined Ditylenchus species found
      in field pea (Pisum sativum L.) grain harvest samples in 2009 and 2010 and from
      C. arvense shoots in pea fields in the Saskatchewan, Alberta, and Manitoba
      provinces. Samples from 538 fields (mainly yellow pea) were provided by 151
      growers throughout the main pea-growing area of the Canadian prairies. Of the
      samples collected, 2% were positive for Ditylenchus. The population density of
      the nematode ranged between 4 and 1,500 nematodes kg(-1) pea harvest sample and
      related to presence of C. arvense seeds. Positive samples occurred in 2009 but
      not in 2010 and were from throughout the pea-growing area of the Canadian
      prairies and not related to cropping history. C. arvense collected from yellow
      pea fields in Saskatchewan and Manitoba, but not Alberta, were infested with
      Ditylenchus. Morphological and molecular (ITS-PCR-RFLP) traits indicated that
      this species belongs to D. weischeri. The results indicated the stem nematode
      found in yellow pea grain is D. weischeri which resided with C. arvense seeds and
      debris to pea samples. Unlike D. dipsaci, D. weischeri is not a nematode pest of
      economic importance; therefore, its presence in the pea harvest samples was not a
      concern. 

PMID- 25580032
TI  - Mixed Methods in Nursing Research : An Overview and Practical Examples.
AB  - Mixed methods research methodologies are increasingly applied in nursing research
      to strengthen the depth and breadth of understanding of nursing phenomena. This
      article describes the background and benefits of using mixed methods research
      methodologies, and provides two examples of nursing research that used mixed
      methods. Mixed methods research produces several benefits. The examples provided
      demonstrate specific benefits in the creation of a culturally congruent picture
      of chronic pain management for American Indians, and the determination of a way
      to assess cost for providing chronic pain care.

PMID- 25580033
TI  - Women in Guam consume more calories during feast days than during non-feast days.
AB  - Parties (feast days) have become increasingly frequent and abundant, in terms of
      food, on the island of Guam. Considering the potential impact of this frequency
      and abundance on food intake, this study compared food intake during feast days
      and non-feast days of women in Guam (25 Chamorros; 24 Filipinas). The women (>=40
      yr) recalled foods they usually consumed during feast days. Subsequently, a 24
      hour dietary recall for a non-feast day was completed by a subsample (n=25).
      Height, weight, and waist circumference were measured to assess obesity status.
      Statistical analyses (paired t-test, ANOVA, and chi-square test) were performed
      with SPSS. Compared to a non-feast day, the women reported higher intakes of
      dietary energy (2645.0 +/- 1125.8 versus 1654.0 +/- 718.8 kcal/day),
      carbohydrates (43.8 +/- 11.5% versus 51.8 +/- 10.2% of kcal), total fat (34.1 +/-
      7.8% versus 27.5 +/- 9.6% of kcal), saturated fat (11.4 +/- 4.7% versus 7.9 +/-
      3.4% of kcal), and sugar (89.5 +/- 62.8 versus 47.3 +/- 42.2 g/day) on feast
      days. Chamorros, compared to Filipinas, reported higher dietary energy density
      (1.7 +/- 0.4 versus 1.4 +/- 0.3 kcal/g), total fat (35.3 +/- 8.9% versus 30.7 +/-
      6.8% of kcal), and saturated fat (12.4 +/- 4.9% versus 9.4 +/- 3.3% of kcal); and
      lower servings of fruit (0.5 +/- 1.0 versus 2.7 +/- 1.8) on feast days. Fourteen
      Chamorros (56.0%) and one Filipina (4.1%) were classified as obese. Current
      feasting behaviors of women in Guam may contribute to obesity if continued for a
      long period. The women would benefit by choosing more fruit and vegetable dishes
      in place of high-energy dishes. Chamorro women would particularly benefit by
      reducing saturated fat intake. Traditional foods, such as taro, breadfruit,
      seafood, fruits, and vegetables, would help accomplish this and thus should be
      promoted at parties on Guam.

PMID- 25580034
TI  - African American Religious Participation.

PMID- 25580035
TI  - IS THERE CONVERGENCE ACROSS COUNTRIES? A SPATIAL APPROACH.
AB  - We analyze convergence across countries over the last half century as a result of
      globalizing forces. Drawing on theories of modernization, dependency, the world
      system, political trade blocs, and the world-society, we consider economic,
      demographic, knowledge, financial, and political dimensions of convergence. Using
      a new methodology, we calculate the minimum volume ellipsoid encompassing
      different groupings of countries, finding that during the 1960-2009 period,
      countries have not evolved significantly closer or similar to one another,
      although groups of countries based on their core-periphery status or membership
      in trade blocs exhibit increasing internal convergence and divergence between one
      another.

PMID- 25580036
TI  - Linking Dichotomous Segregation with Multi-group Segregation: Weighted
      Segregation Ratios in Selected U. S. Metropolitan Areas.
AB  - The U. S. residential landscape is increasingly multi-racial and multi-ethnic,
      giving rise to the question of how to compare dichotomous segregation among
      multiple groups living in the same area. To address the problem in the existing
      dichotomous approach, which offers no common basis for comparing dichotomous
      segregation among multiple groups, this paper develops a weighted segregation
      ratio approach based on Theil's segregation index and its additive
      decomposability. This approach can be used to bridge information obtained from
      dichotomous segregation between specific groups (such as black-white and black
      Hispanic), and dichotomous segregation between group and non-group (such as white
      non-white and black-non-black) in previous studies. We apply both dichotomous and
      weighted segregation ratio approaches to 1990 and 2000 U. S. census data. Results
      are interpreted for five selected metropolitan areas as well as for the weighted
      national average. This new approach yields distinctive findings that portray the
      complicated process of residential segregation, including the increasing
      significance of Hispanic segregation and Asian segregation in the decade from
      1990 to 2000.

PMID- 25580037
TI  - Sensitivity analysis for contagion effects in social networks.
AB  - Analyses of social network data have suggested that obesity, smoking, happiness
      and loneliness all travel through social networks. Individuals exert "contagion
      effects" on one another through social ties and association. These analyses have
      come under critique because of the possibility that homophily from unmeasured
      factors may explain these statistical associations and because similar findings
      can be obtained when the same methodology is applied to height, acne and head
      aches, for which the conclusion of contagion effects seems somewhat less
      plausible. We use sensitivity analysis techniques to assess the extent to which
      supposed contagion effects for obesity, smoking, happiness and loneliness might
      be explained away by homophily or confounding and the extent to which the
      critique using analysis of data on height, acne and head-aches is relevant.
      Sensitivity analyses suggest that contagion effects for obesity and smoking
      cessation are reasonably robust to possible latent homophily or environmental
      confounding; those for happiness and loneliness are somewhat less so. Supposed
      effects for height, acne and head-aches are all easily explained away by latent
      homophily and confounding. The methodology that has been employed in past studies
      for contagion effects in social networks, when used in conjunction with
      sensitivity analysis, may prove useful in establishing social influence for
      various behaviors and states. The sensitivity analysis approach can be used to
      address the critique of latent homophily as a possible explanation of
      associations interpreted as contagion effects.

PMID- 25580039
TI  - ADAPTIVE ROBUST VARIABLE SELECTION.
AB  - Heavy-tailed high-dimensional data are commonly encountered in various scientific
      fields and pose great challenges to modern statistical analysis. A natural
      procedure to address this problem is to use penalized quantile regression with
      weighted L1-penalty, called weighted robust Lasso (WR-Lasso), in which weights
      are introduced to ameliorate the bias problem induced by the L1-penalty. In the
      ultra-high dimensional setting, where the dimensionality can grow exponentially
      with the sample size, we investigate the model selection oracle property and
      establish the asymptotic normality of the WR-Lasso. We show that only mild
      conditions on the model error distribution are needed. Our theoretical results
      also reveal that adaptive choice of the weight vector is essential for the WR
      Lasso to enjoy these nice asymptotic properties. To make the WR-Lasso practically
      feasible, we propose a two-step procedure, called adaptive robust Lasso (AR
      Lasso), in which the weight vector in the second step is constructed based on the
      L1-penalized quantile regression estimate from the first step. This two-step
      procedure is justified theoretically to possess the oracle property and the
      asymptotic normality. Numerical studies demonstrate the favorable finite-sample
      performance of the AR-Lasso.

PMID- 25580040
TI  - Endogeneity in High Dimensions.
AB  - Most papers on high-dimensional statistics are based on the assumption that none
      of the regressors are correlated with the regression error, namely, they are
      exogenous. Yet, endogeneity can arise incidentally from a large pool of
      regressors in a high-dimensional regression. This causes the inconsistency of the
      penalized least-squares method and possible false scientific discoveries. A
      necessary condition for model selection consistency of a general class of
      penalized regression methods is given, which allows us to prove formally the
      inconsistency claim. To cope with the incidental endogeneity, we construct a
      novel penalized focused generalized method of moments (FGMM) criterion function.
      The FGMM effectively achieves the dimension reduction and applies the
      instrumental variable methods. We show that it possesses the oracle property even
      in the presence of endogenous predictors, and that the solution is also near
      global minimum under the over-identification assumption. Finally, we also show
      how the semi-parametric efficiency of estimation can be achieved via a two-step
      approach.

PMID- 25580041
TI  - A Note on Disappearing Veterans.
AB  - In this research note, the rapid decline of the veteran population in the United
      States from 1980 to 2010 is outlined. The decline in the veteran population has
      been accompanied by an increasing concentration of veterans in smaller, more
      rural counties, often surrounding military bases. The result is that there has
      been a consistent increase in the residential segregation of veterans from the
      nonveteran population.

PMID- 25580038
TI  - The Eye Specification Network in Drosophila.
AB  - One of the most exciting revelations in retinal biology is the realization that
      the molecules and mechanisms that regulate eye development have been conserved in
      all seeing animals including such diverse organisms as the fruit fly, mouse and
      man. The emerging commonality among mechanisms used in eye development allows for
      the use of model systems such as the fruit fly, Drosophila melanogaster, to
      provide key insights into the development and diseases of the mammalian eye. Eye
      specification in Drosophila is controlled, in part, by the concerted activities
      of eight nuclear proteins and several signal transduction cascades that together
      form a tightly woven regulatory network. Loss of function mutations in several
      components lead to the complete derailment of eye development while ectopic
      expression of threse genes in non-retinal tissues can direct the fates of these
      tissues towards eye formation. Here we will describe what is currently known
      about this remarkable regulatory cassettee highlight some of the outstanding
      questions that still need to be answered.

PMID- 25580042
TI  - SparseNet: Coordinate Descent With Nonconvex Penalties.
AB  - We address the problem of sparse selection in linear models. A number of
      nonconvex penalties have been proposed in the literature for this purpose, along
      with a variety of convex-relaxation algorithms for finding good solutions. In
      this article we pursue a coordinate-descent approach for optimization, and study
      its convergence properties. We characterize the properties of penalties suitable
      for this approach, study their corresponding threshold functions, and describe a
      df-standardizing reparametrization that assists our pathwise algorithm. The MC+
      penalty is ideally suited to this task, and we use it to demonstrate the
      performance of our algorithm. Certain technical derivations and experiments
      related to this article are included in the Supplementary Materials section.

PMID- 25580043
TI  - Midlife as a Pivotal Period in the Life Course: Balancing Growth and Decline at
      the Crossroads of Youth and Old Age.
AB  - We provide evidence for multidirectionality, variability, and plasticity in the
      nature and direction of change in physical health, cognitive functioning, and
      well-being during the middle years of the life course. The picture of well-being
      in midlife based on longitudinal data from the Midlife in the United States
      (MIDUS) study is a more positive one than portrayed in previous cross-sectional
      studies. We present middle age as a pivotal period in the life course in terms of
      balancing growth and decline, linking earlier and later periods of life, and
      bridging younger and older generations. We highlight the role of protective
      factors and multisystem resilience in mitigating declines. Those in middle age
      play a central role in the lives of those who are younger and older at home, in
      the workplace, and in society at large. Thus, a focus on promoting health and
      well-being in middle age can have a far-reaching impact.

PMID- 25580044
TI  - Promoting careers in health care for urban youth: What students, parents and
      educators can teach us.
AB  - There are many obstacles that urban youth experience in pursuing health careers,
      but the benefits of diversifying the classroom and workforce are clear. This is
      especially true today as educators and policymakers seek to enhance
      underrepresented minority students' access to health careers, and also achieve
      the health workforce needed to support the Affordable Care Act. The creation of
      student pipeline programs began more than 40 years ago, but success has been
      equivocal. In 2008, Mentoring in Medicine (MIM) conducted a research project to
      identify how students learn about health careers; develop strategies for an
      integrated, experiential learning program that encourages underrepresented
      minority students to pursue careers in health; and translate these into best
      practices for supporting students through their entire preparatory journey. Six
      focus groups were conducted with educators, students, and their parents. The
      inclusion of parents was unusual in studies of this kind. The outcome yielded
      important and surprising differences between student and parent knowledge,
      attitudes and beliefs. They informed our understanding of the factors that
      motivate and deter underrepresented minority students to pursue careers in health
      care. Specific programmatic strategies emerged that found their place in the
      subsequent development of new MIM programming that falls into the following three
      categories: community-based, school-based and Internet based. Best practices
      derived from these MIM programs are summarized and offered for consideration by
      other health career education program developers targeting underrepresented
      minority students, particularly those located in urban settings.

PMID- 25580045
TI  - Veteran Status and Body Weight: A Longitudinal Fixed-Effects Approach.
AB  - About 10-12 % of young men (and increasingly, women) have served a term in the
      military. Yet, we know relatively little about the consequences of military
      service for the lives of those who serve. In this article, we provide estimates
      of the relationship between men's peacetime military service during the all
      volunteer era (AVE) and body weight using longitudinal data on 6,304 men taken
      from the National Longitudinal Survey of 1979 (NLSY-79). Using fixed-effects
      estimators on up to 13 years of data and numerous controls for time-varying life
      course characteristics linked to body weight, we find that veterans of active
      duty military service have higher levels of BMI and obesity. We argue that eating
      habits learned during service, coupled with patterns of physical activity, lead
      to a situation whereby veterans making the transition to less active civilian
      lifestyles gain weight that is not lost over time.

PMID- 25580046
TI  - Fluid-structure interaction analysis of bioprosthetic heart valves: Significance
      of arterial wall deformation.
AB  - We propose a framework that combines variational immersed-boundary and arbitrary
      Lagrangian-Eulerian (ALE) methods for fluid-structure interaction (FSI)
      simulation of a bioprosthetic heart valve implanted in an artery that is allowed
      to deform in the model. We find that the variational immersed-boundary method for
      FSI remains robust and effective for heart valve analysis when the background
      fluid mesh undergoes deformations corresponding to the expansion and contraction
      of the elastic artery. Furthermore, the computations presented in this work show
      that the arterial wall deformation contributes significantly to the realism of
      the simulation results, leading to flow rates and valve motions that more closely
      resemble those observed in practice.

PMID- 25580047
TI  - Community Violence Exposure and Callous-Unemotional Traits in Adolescents:
      Testing Parental Support as a Promotive Versus Protective Factor.
AB  - Although callous-unemotional (CU) traits are associated with maladjustment in
      youth, literature predicting CU using prospective designs is rare. In the present
      study we examine associations between exposure to community violence, supportive
      relationships with caregivers, and CU in a sample of 236 low-income youth (M age
      = 13.00 yrs, SD = 1.56 yrs; 43% male; 92% African American) participating in a 3
      wave longitudinal study of violence exposure and adjustment. Both promotive and
      protective models of linkages between exposure to community violence, support,
      and CU were investigated. Given known sex differences in CU, sex was explored as
      a moderator. Regression analysis revealed that witnessing and hearing about
      community violence, aggregated over 2 waves, were positively associated with CU
      at the final study wave. Supportive relationships with caregivers, aggregated
      over 2 waves, were negatively associated with CU but did not interact with
      violence exposure, suggesting that supportive relationships with caregivers has a
      promotive but not a protective association with CU in the context of exposure to
      violence. The pattern of associations did not vary by sex. This study informs our
      understanding of factors that contribute to the development of CU.

PMID- 25580049
TI  - Sampling in Developmental Science: Situations, Shortcomings, Solutions, and
      Standards.
AB  - Sampling is a key feature of every study in developmental science. Although
      sampling has far-reaching implications, too little attention is paid to sampling.
      Here, we describe, discuss, and evaluate four prominent sampling strategies in
      developmental science: population-based probability sampling, convenience
      sampling, quota sampling, and homogeneous sampling. We then judge these sampling
      strategies by five criteria: whether they yield representative and generalizable
      estimates of a study's target population, whether they yield representative and
      generalizable estimates of subsamples within a study's target population, the
      recruitment efforts and costs they entail, whether they yield sufficient power to
      detect subsample differences, and whether they introduce "noise" related to
      variation in subsamples and whether that "noise" can be accounted for
      statistically. We use sample composition of gender, ethnicity, and socioeconomic
      status to illustrate and assess the four sampling strategies. Finally, we tally
      the use of the four sampling strategies in five prominent developmental science
      journals and make recommendations about best practices for sample selection and
      reporting.

PMID- 25580048
TI  - Biomarkers in the primary progressive aphasias.
AB  - BACKGROUND: Primary progressive aphasia (PPA) is a progressive disorder of
      language that is increasingly recognised as an important presentation of a
      specific spectrum of neurodegenerative conditions. AIMS: In an era of
      etiologically specific treatments for neurodegenerative conditions, it is crucial
      to establish the histopathologic basis for PPA. In this review, I discuss
      biomarkers for identifying the pathology underlying PPA. MAIN CONTRIBUTION:
      Clinical syndromes suggest a probabilistic association between a specific PPA
      variant and an underlying pathology, but there are also many exceptions. A
      considerable body of work with biomarkers is now emerging as an important
      addition to clinical diagnosis. I review genetic, neuroimaging and biofluid
      studies that can help determine the pathologic basis for PPA. CONCLUSIONS:
      Together with careful clinical examination, there is great promise that
      supplemental biomarker assessments will lead to accurate diagnosis of the
      pathology associated with PPA during life and serve as the basis for clinical
      trials in this spectrum of disease.

PMID- 25580052
TI  - A MagDot-Nanoconveyor Assay Detects and Isolates Molecular Biomarkers.
AB  - The ability to quickly analyze, separate, and manipulate multiple types of
      biomarkers from small sample volumes is a significant step toward personalized
      medicine.

PMID- 25580051
TI  - Red cell distribution width is associated with presence, stage, and grade in
      patients with renal cell carcinoma.
AB  - It has been reported that red blood cell width (RDW) is a marker associated with
      the presence and adverse outcomes of various diseases. However, no data are
      available on the correlation of RDW with presence, stage, and grade in patients
      with renal cell carcinoma (RCC) yet. By retrospectively analyzing clinical and
      laboratory data at baseline of histologically confirmed RCC cases and controls,
      the present study demonstrated that the RDW values were significantly higher in
      patients with RCC than those in controls, and the baseline RDW value was
      independently associated with the presence of RCC. Besides, the data revealed a
      positive association between RCC stage and grade and the level of RDW. These
      findings may have important clinical implications due to future application using
      a RDW value in predicting RCC. 

PMID- 25580053
TI  - ASIAN AMERICAN-WHITE DIFFERENCES IN THE EFFECT OF MOTHERHOOD ON CAREER OUTCOMES.
AB  - U.S.-born Asian Americans are unique among American minority groups in that they
      lack earnings disadvantages relative to Whites with similar education levels.
      Controlling for education and age, there is little difference in the earnings of
      U.S.-born Asian and White men, but Asian women have higher earnings than
      comparable White women. Using data from SESTAT, this study tests the hypothesis
      that Asian American women's high earnings may result from adjusting their labor
      supply less than White women in response to parenthood, leading to greater work
      experience over time. Findings show that Asian American women are less likely
      than White women reduce labor supply in response to parenthood, and that their
      resulting greater work experience explains their high rate of earnings growth.

PMID- 25580054
TI  - Think globally, act globally: An epidemiologist's perspective on instrumental
      variable estimation.
AB  - We appreciated Imbens' summary and reflections on the state of instrumental
      variable (IV) methods from an econometrician's perspective. His review was much
      needed as it clarified several issues that have been historically a source of
      confusion when individuals from different disciplines discussed IV methods. Among
      the many topics covered by Imbens, we would like to focus on the common choice of
      the local average treatment effect (LATE) over the "global" average treatment
      effect (ATE) in IV analyses of epidemiologic data. As Imbens acknowledges, this
      choice of the LATE as an estimand has been contentious (Angrist, Imbens and
      Rubin, 1996; Robins and Greenland, 1996; Deaton, 2010; Imbens, 2010; Pearl,
      2011). Several authors have questioned the usefulness of the LATE for informing
      clinical practice and policy decisions, because it only pertains to an unknown
      subset of the population of interest: the so-called "compliers". To make things
      worse, many studies do not even report the expected proportion of compliers in
      the study population (Swanson and Hernan, 2013). Other authors have wondered
      whether the LATE is advocated for simply because of the relatively weaker
      assumptions required for its identification, analogous to the drunk who stays
      close to the lamp post and declares whatever he finds under its light is what he
      was looking for all along (Deaton, 2010). Here we explore the limitations of the
      LATE in the context of epidemiologic and public health research. First we discuss
      the relevance of LATE as an effect measure and conclude that it is not our
      primary choice. Second, we discuss the tenability of the monotonicity condition
      and conclude that this assumption is not a plausible one in many common settings.
      Finally, we propose further alternatives to the LATE, beyond those discussed by
      Imbens, that refocus on the global ATE in the population of interest.

PMID- 25580050
TI  - Proteomic analysis of serum and urine of HIV-monoinfected and HIV/HCV-coinfected
      patients undergoing long term treatment with nevirapine.
AB  - Nevirapine (NVP) is an effective nonnucleoside reverse transcriptase inhibitor
      (NNRTI) of particular interest as it is often used in resource limited countries.
      However, one of the main concerns with the use of NVP is hepatotoxicity and
      elevation of liver enzymes as a consequence of highly active antiretroviral
      therapy (HAART) containing NVP is more often reported in HIV patients coinfected
      with hepatitis C virus than in HIV-monoinfected patients. To discover possible
      markers of NVP induced hepatotoxicity, serum and urine samples from twenty-five
      HIV or HIV/HCV patients, all of whom had received NVP continuously for at least
      four months, and healthy controls were subjected to in-solution or in-gel
      proteomic analysis. A total of 83 differentially regulated proteins consisted of
      34 proteins identified in serum by in-solution analysis, 2 proteins identified
      from serum in a 2D gel electrophoresis analysis, and 47 proteins identified in
      urine in an in-solution analysis. Three proteins, namely, haptoglobin, Rho
      related BTB domain containing protein 3, and death-associated protein kinase 3,
      were selected for further validation by Western blot analysis and results showed
      that haptoglobin has potential for further development as an additional marker of
      NVP induced hepatotoxicity. 

PMID- 25580055
TI  - PLANNING AND RESPONSE IN THE AFTERMATH OF A LARGE CRISIS: AN AGENT-BASED
      INFORMATICS FRAMEWORK*
AB  - We present a synthetic information and modeling environment that can allow policy
      makers to study various counter-factual experiments in the event of a large human
      initiated crisis. The specific scenario we consider is a ground detonation caused
      by an improvised nuclear device in a large urban region. In contrast to earlier
      work in this area that focuses largely on the prompt effects on human health and
      injury, we focus on co-evolution of individual and collective behavior and its
      interaction with the differentially damaged infrastructure. This allows us to
      study short term secondary and tertiary effects. The present environment is
      suitable for studying the dynamical outcomes over a two week period after the
      initial blast. A novel computing and data processing architecture is described;
      the architecture allows us to represent multiple co-evolving infrastructures and
      social networks at a highly resolved temporal, spatial, and individual scale. The
      representation allows us to study the emergent behavior of individuals as well as
      specific strategies to reduce casualties and injuries that exploit the spatial
      and temporal nature of the secondary and tertiary effects. A number of important
      conclusions are obtained using the modeling environment. For example, the studies
      decisively show that deploying ad hoc communication networks to reach individuals
      in the affected area is likely to have a significant impact on the overall
      casualties and injuries.

PMID- 25580057
TI  - Micromachined "Side-Viewing" Optical Sensor Probe for Detection of Esophageal
      Cancers.
AB  - In this paper, we report the design, fabrication and testing of a new
      miniaturized optical sensor probe with "side viewing" capability for oblique
      incidence diffuse reflectance spectrometry. The sensor probe consists of a
      lithographically patterned polymer waveguides chip and two micromachined
      positioning substrates and source/collection fibers to achieve 45 degrees  light
      incidence and collection of spatially resolved diffuse reflectance. Diffuse
      reflectance of human esophageal surface has been successfully measured for
      differentiation of cancerous tissues from normal ones.

PMID- 25580056
TI  - Genetic and Environmental Influences on Individual Differences in Frequency of
      Play with Pets among Middle-Aged Men: A Behavioral Genetic Analysis.
AB  - There is growing evidence that pet ownership and human-animal interaction (HAI)
      have benefits for human physical and psychological well-being. However, there may
      be pre-existing characteristics related to patterns of pet ownership and
      interactions with pets that could potentially bias results of research on HAI.
      The present study uses a behavioral genetic design to estimate the degree to
      which genetic and environmental factors contribute to individual differences in
      frequency of play with pets among adult men. Participants were from the ongoing
      longitudinal Vietnam Era Twin Study of Aging (VETSA), a population-based sample
      of 1,237 monozygotic (MZ) and dizygotic (DZ) twins aged 51-60 years. Results
      demonstrate that MZ twins have higher correlations than DZ twins on frequency of
      pet play, suggesting that genetic factors play a role in individual differences
      in interactions with pets. Structural equation modeling revealed that, according
      to the best model, genetic factors accounted for as much as 37% of the variance
      in pet play, although the majority of variance (63-71%) was due to environmental
      factors that are unique to each twin. Shared environmental factors, which would
      include childhood exposure to pets, overall accounted for <10% of the variance in
      adult frequency of pet play, and were not statistically significant. These
      results suggest that the effects of childhood exposure to pets on pet ownership
      and interaction patterns in adulthood may be mediated primarily by genetically
      influenced characteristics.

PMID- 25580058
TI  - Mechanistic Study on the Reduction of SWCNT-induced Cytotoxicity by Albumin
      Coating.
AB  - Single walled carbon nanotubes (SWCNTs) are utilized in many areas, accompanied
      with the ever rising safety concerns. Coating the SWCNTs by serum albumin has
      shown promises in reduction of their cytotoxicity. The cause of toxicity
      reduction could be due to the blockage of cellular protein adsorption by bovine
      serum albumin (BSA). Here, our study explored the mechanism of toxicity reduction
      from the point of view of protein adsorption. Different loadings of BSA led to
      varied surface coverage of the SWCNTs, which was positively related to the level
      of cytotoxicity. In addition, the BSA-coated SWCNTs were tested for their surface
      morphology change, cellular uptake, and adsorption of cellular proteins. BSA
      could be competed off the SWCNT surface by the cytosol proteins, and thus a
      higher BSA loading was needed to provide better protection to the cells. Cellular
      uptake was also reduced with a higher BSA loading. Moreover, the BSA coating
      changed the surface property of SWCNTs, and as a consequence, altered the types
      of proteins adsorbed by the SWCNTs. Our results support that adsorption of BSA
      reduces cellular uptake of SWCNTs as well as adsorption of cellular proteins on
      SWCNTs, both contributing to the much lower cytotoxicity observed for the BSA
      coated SWCNTs.

PMID- 25580059
TI  - Genetic Programming and Frequent Itemset Mining to Identify Feature Selection
      Patterns of iEEG and fMRI Epilepsy Data.
AB  - Pattern classification for intracranial electroencephalogram (iEEG) and
      functional magnetic resonance imaging (fMRI) signals has furthered epilepsy
      research toward understanding the origin of epileptic seizures and localizing
      dysfunctional brain tissue for treatment. Prior research has demonstrated that
      implicitly selecting features with a genetic programming (GP) algorithm more
      effectively determined the proper features to discern biomarker and non-biomarker
      interictal iEEG and fMRI activity than conventional feature selection approaches.
      However for each the iEEG and fMRI modalities, it is still uncertain whether the
      stochastic properties of indirect feature selection with a GP yield (a)
      consistent results within a patient data set and (b) features that are specific
      or universal across multiple patient data sets. We examined the reproducibility
      of implicitly selecting features to classify interictal activity using a GP
      algorithm by performing several selection trials and subsequent frequent itemset
      mining (FIM) for separate iEEG and fMRI epilepsy patient data. We observed within
      subject consistency and across-subject variability with some small similarity for
      selected features, indicating a clear need for patient-specific features and
      possible need for patient-specific feature selection or/and classification. For
      the fMRI, using nearest-neighbor classification and 30 GP generations, we
      obtained over 60% median sensitivity and over 60% median selectivity. For the
      iEEG, using nearest-neighbor classification and 30 GP generations, we obtained
      over 65% median sensitivity and over 65% median selectivity except one patient.

PMID- 25580060
TI  - Effect of low-dose, long-term roxithromycin on airway inflammation and remodeling
      of stable noncystic fibrosis bronchiectasis.
AB  - BACKGROUND: Noncystic fibrosis bronchiectasis (NCFB) is characterized by airway
      expansion and recurrent acute exacerbations. Macrolide has been shown to exhibit
      anti-inflammatory effects in some chronic airway diseases. OBJECTIVE: To assess
      the efficacy of roxithromycin on airway inflammation and remodeling in patients
      with NCFB under steady state. METHODS: The study involved an open-label design in
      52 eligible Chinese patients with NCFB, who were assigned to control (receiving
      no treatment) and roxithromycin (receiving 150 mg/day for 6 months) groups. At
      baseline and 6 months, the inflammatory markers such as interleukin- (IL-)8,
      neutrophil elastase (NE), matrix metalloproteinase- (MMP)9, hyaluronidase (HA),
      and type IV collagen in sputum were measured, along with the detection of dilated
      bronchus by throat computed tomography scan, and assessed the exacerbation.
      RESULTS: Forty-three patients completed the study. The neutrophil in the sputum
      was decreased in roxithromycin group compared with control (P < 0.05). IL-8, NE,
      MMP-9, HA, and type IV collagen in sputum were also decreased in roxithromycin
      group compared with the control group (all P < 0.01). Airway thickness of dilated
      bronchus and exacerbation were reduced in roxithromycin group compared with the
      control (all P < 0.05). CONCLUSIONS: Roxithromycin can reduce airway inflammation
      and airway thickness of dilated bronchus in patients with NCFB.

PMID- 25580061
TI  - The roles of CD147 and/or cyclophilin A in kidney diseases.
AB  - CD147 is a widely expressed integral plasma membrane glycoprotein and has been
      involved in a variety of physiological and pathological activities in combination
      with different partners, including cyclophilins, caveolin-1, monocarboxylate
      transporters, and integrins. Recent data demonstrate that both CyPA and CD147
      significantly contribute to renal inflammation, acute kidney injury, renal
      fibrosis, and renal cell carcinoma. Here we review the current understanding of
      cyclophilin A and CD147 expression and functions in kidney diseases and potential
      implications for treatment of kidney diseases. 

PMID- 25580063
TI  - Epidemic spread in networks: Existing methods and current challenges.
AB  - We consider the spread of infectious disease through contact networks of
      Configuration Model type. We assume that the disease spreads through contacts and
      infected individuals recover into an immune state. We discuss a number of
      existing mathematical models used to investigate this system, and show relations
      between the underlying assumptions of the models. In the process we offer
      simplifications of some of the existing models. The distinctions between the
      underlying assumptions are subtle, and in many if not most cases this subtlety is
      irrelevant. Indeed, under appropriate conditions the models are equivalent. We
      compare the benefits and disadvantages of the different models, and discuss their
      application to other populations (e.g., clustered networks). Finally we discuss
      ongoing challenges for network-based epidemic modeling.

PMID- 25580062
TI  - The therapeutic benefits of perceptual learning.
AB  - The modern field of perceptual learning addresses improvements of sensory and
      perceptual functioning in adult observers and provides powerful tools to
      ameliorate the effects of neurological conditions that involve a sensory or
      attentional deficit. While the sensory systems were once thought to be plastic
      only during early development, modern research demonstrates a great deal of
      plasticity in the adult brain. Here we discuss the value of perceptual learning
      as a method to improve sensory and attentional function, with a brief overview of
      the current approaches in the field, including how perceptual learning can be
      highly specific to the training set, and also how new training approaches can
      overcome this specificity and transfer learning effects to untrained tasks. We
      discuss these in the context of extant applications of perceptual learning as a
      treatment for neurological conditions and how new knowledge mechanisms (including
      attention, exposure based learning, reinforcement learning and multisensory
      facilitation) that allow or restrict learning in the visual system can lead to
      enhanced treatment approaches. We suggest new approaches that integrate multiple
      mechanisms of perceptual learning that promise greater learning and more
      generalization to real world conditions.

PMID- 25580064
TI  - Pairwise and edge-based models of epidemic dynamics on correlated weighted
      networks.
AB  - In this paper we explore the potential of the pairwise-type modelling approach to
      be extended to weighted networks where nodal degree and weights are not
      independent. As a baseline or null model for weighted networks, we consider
      undirected, heterogenous networks where edge weights are randomly distributed. We
      show that the pairwise model successfully captures the extra complexity of the
      network, but does this at the cost of limited analytical tractability due the
      high number of equations. To circumvent this problem, we employ the edge-based
      modelling approach to derive models corresponding to two different cases, namely
      for degree-dependent and randomly distributed weights. These models are more
      amenable to compute important epidemic descriptors, such as early growth rate and
      final epidemic size, and produce similarly excellent agreement with simulation.
      Using a branching process approach we compute the basic reproductive ratio for
      both models and discuss the implication of random and correlated weight
      distributions on this as well as on the time evolution and final outcome of
      epidemics. Finally, we illustrate that the two seemingly different modelling
      approaches, pairwsie and edge-based, operate on similar assumptions and it is
      possible to formally link the two.

PMID- 25580065
TI  - Heterogeneity of The CD90+ Population in Different Stages of
      Hepatocarcinogenesis.
AB  - We have characterized herein the heterogeneity of the CD90+ population at each
      stage of hepatocarcinogenesis using a computer-assisted immunohistochemical
      staining evaluation method for quantitative analysis on tissue microarrays. We
      found that CD90 in Hepatocellular carcinoma (HCC) tissues, which has been shown
      to be a marker for cancer stem cells, is expressed on tumor cells, in the stroma
      or on endothelial cells. Sub-classification of the CD90+ population was based on
      morphology and co-expression with known markers including CD45 and CD31. Multiple
      linear regression suggested that the percentage of CD90+ cancer cells/hepatocyte
      (p<0.0001), level of overall CD90 expression (p<0.0014), and level of CD90
      expression in tumor islands (p<0.0001) increased significantly in each stage of
      liver disease progression, while the level of stromal CD90 expression (p=0.1129)
      did not change significantly. Additionally, only the CD90+ cancer cells were
      positive for other cancer stem cell (CSC) markers including CD24, CD44 and CD133
      whereas the other CD90+ cells were negative for these markers. CD90 expression in
      cirrhosis was observed in hepatocytes, the portal tract area and fibrous septa
      while CD90 expression in normal liver was limited only to the portal tract area.
      This study demonstrates the heterogeneity of the CD90+ population in HCC where a
      small population of the CD90+ cells that expressed other CSC markers are CSCs and
      are associated with advanced stages of hepatocarcinogenesis. This heterogeneity
      should be emphasized in further studies where other methods may not be able to
      discriminate these distinct types of CD90+ cells.

PMID- 25580066
TI  - The Temporal Effects of Divorces and Separations on Children's Academic
      Achievement and Problem Behavior.
AB  - This paper provides an examination of the effects of the divorce and separation
      process on children's academic achievement over time. By using child fixed
      effects and establishing a baseline period that is 4-or-more years prior to a
      family disruption, I can examine how children are affected in different periods
      relative to the disruption and whether any negative effects subside, persist, or
      escalate as time passes from the disruption. With a sample of 7-14 year olds, I
      find: children are affected at least 2-4 years before the disruption; reading
      test scores are most affected; and for Reading Comprehension, the negative
      effects persist and even escalate as time passes from the disruption.

PMID- 25580068
TI  - A 0.6 T/650 mm RT Bore Solid Nitrogen Cooled MgB2 Demonstration Coil for MRI-a
      Status Report.
AB  - Aiming to demonstrate feasibility and practicality of a low cost superconducting
      MRI magnet system targeted for use in small hospitals, rural communities and
      underdeveloped countries, MIT-Francis Bitter Magnet Laboratory has developed a
      0.6 T/650 mm room temperature bore demonstration coil wound with multifilament
      MgB2 conductor and cooled via an innovative cryogenic design/operation. The coil
      is to be maintained cold by solid nitrogen kept in the solid state by a
      cryocooler. In the event of a power failure the cryocooler is automatically
      thermally decoupled from the system. In this paper we present details of the MgB2
      conductor, winding process, and preliminary theoretical analysis of the current
      carrying performance of the conductively cooled coils in zero background field
      and over the 10-30 K temperature range.

PMID- 25580067
TI  - Individual Patient and Program Factors Related to Prison and Community Treatment
      Completion in Prison-Initiated Methadone Maintenance Treatment.
AB  - While prison-initiated methadone maintenance treatment is effective, it is
      largely unknown as to what patient and program factors are related to outcomes.
      These issues were studied in a secondary analysis of data from 67 male prerelease
      prison inmates with preincarceration heroin addiction. Three outcomes are
      examined: completed prison treatment; completed 1 year of community treatment;
      and number of days in community treatment. Being employed (p = .045) during the
      three years prior to index incarceration was significantly and positively related
      to community treatment completion. Increased frequency of urine tests taken was
      significantly associated with a greater number of days in community treatment (p
      < .001). Limitations, policy implications, and directions for future research are
      discussed.

PMID- 25580069
TI  - An Algorithm for Optimal Tapered Matching, With Application to Disparities in
      Survival.
AB  - In a tapered matched comparison, one group of individuals, called the focal
      group, is compared to two or more nonoverlapping matched comparison groups
      constructed from one population in such a way that successive comparison groups
      increasingly resemble the focal group. An optimally tapered matching solves two
      problems simultaneously: it optimally divides the single comparison population
      into nonoverlapping comparison groups and optimally pairs members of the focal
      group with members of each comparison group. We show how to use the optimal
      assignment algorithm in a new way to solve the optimally tapered matching
      problem, with implementation in R. This issue often arises in studies of groups
      Defined by race, gender, or other categorizations such that equitable public
      policy might require an understanding of the mechanisms that produce disparate
      outcomes, where certain specific mechanisms would be judged illegitimate,
      necessitating reform. In particular, we use data from Medicare and the SEER
      Program of the National Cancer Institute as part of an ongoing study of black
      white disparities in survival among women with endometrial cancer.

PMID- 25580070
TI  - Multivariate General Linear Models (MGLM) on Riemannian Manifolds with
      Applications to Statistical Analysis of Diffusion Weighted Images.
AB  - Linear regression is a parametric model which is ubiquitous in scientific
      analysis. The classical setup where the observations and responses, i.e., (xi ,
      yi ) pairs, are Euclidean is well studied. The setting where yi is manifold
      valued is a topic of much interest, motivated by applications in shape analysis,
      topic modeling, and medical imaging. Recent work gives strategies for max-margin
      classifiers, principal components analysis, and dictionary learning on certain
      types of manifolds. For parametric regression specifically, results within the
      last year provide mechanisms to regress one real-valued parameter, xi ? R,
      against a manifold-valued variable, yi ? . We seek to substantially extend the
      operating range of such methods by deriving schemes for multivariate multiple
      linear regression -a manifold-valued dependent variable against multiple
      independent variables, i.e., f : Rn -> . Our variational algorithm efficiently
      solves for multiple geodesic bases on the manifold concurrently via gradient
      updates. This allows us to answer questions such as: what is the relationship of
      the measurement at voxel y to disease when conditioned on age and gender. We show
      applications to statistical analysis of diffusion weighted images, which give
      rise to regression tasks on the manifold GL(n)/O(n) for diffusion tensor images
      (DTI) and the Hilbert unit sphere for orientation distribution functions (ODF)
      from high angular resolution acquisition. The companion open-source code is
      available on nitrc.org/projects/riem_mglm.

PMID- 25580071
TI  - Severe Asthma: The Evolution of Patient-directed Management.
AB  - Severe asthma has been increasingly recognized as a heterogenous disease with
      varied clinical characteristics and pathophysiological processes. Patients with
      severe asthma suffer significant impairment in their daily life and impose a
      substantial burden on health care resources. The recent work of consortia groups
      has led to an improved definition of severe asthma as well as better
      characterization of the patients with severe disease. Different approaches,
      including unbiased cluster analyses, have been utilized to identify severe asthma
      phenotypes (subgroups) defined by their clinical characteristics and immune
      processes. Recognition of severe asthma phenotypes has assisted the development
      of targeted therapies by identifying patients more likely to respond to the
      specific agent. In this article, we discuss the evolution of our understanding of
      severe asthma and review the currently available therapies and promising drugs in
      development. In addition, we examine the role of bronchoscopy in severe asthma
      and the emerging evidence regarding bronchial thermoplasty.

PMID- 25580072
TI  - Recent progress on countercurrent chromatography modeling.
AB  - As countercurrent chromatography is becoming an established method in
      chromatography for many kinds of products, it is becoming increasingly important
      to model the process and to be able to predict the peaks for a given process. The
      CCC industries are looking for rapid methods to analyze the processes of
      countercurrent chromatography and select suitable solvent system. In this paper,
      recent progress is reviewed in the development and demonstration of several types
      of models of countercurrent chromatography. Literature lists a number of
      countercurrent chromatography (CCC) models that can predict the retention time
      and to a certain extent the peak width of a solute eluting from a CCC column,
      such as cell model, CCD model, CSTRs model, probabilistic model, temperature
      dependence plate model, physical models, etc.

PMID- 25580073
TI  - New Research Findings: Executive Functions of Adolescents Who Use Cochlear
      Implants.

PMID- 25580075
TI  - Structure of Microemulsion Formulated with Monoacylglycerols in the Presence of
      Polyols and Ethanol.
AB  - The influence of polyols as cosurfactants (propylene glycol PG; glycerol G) and
      short chain alcohol as a cosolvent (ethanol EtOH) on the formation and
      solubilization capacity of the systems: hexadecane/monoacylglycerols
      (MAG)/polyol/water:EtOH, at 60  degrees C, was investigated. Electrical
      conductivity measurement, and the DSC method were applied to determine the
      structure and type of microemulsions formed. The dimension of the droplets was
      characterized by DLS. It has been stated that concentration of EtOH has a strong
      influence on the shape and extend the microemulsion areas and helps to avoid
      rigid structures such as gels, precipitates, and liquid crystals. It was found
      that, depending on the concentration of five-component systems, it was possible
      to obtain fully diluted microemulsions with dispersed particles size distribution
      ranging from 5 to 30 nm. Studied systems are changing the w/o structure into a
      bicontinuous system. The results of electrical conductivity showed that the
      electrical percolation threshold is dependent on the hydration of polar head
      groups in the whole system and the less rigid interfacial film due to the
      intercalation of ethanol. In addition, the surfactant/alcohol/polyol can strongly
      bind water in the inner phase so that it freezes below -10  degrees C and acts in
      part as 'bound' water. In the systems containing more than 50 mass% of polyols,
      with respect to the water, the all the water was non-freezable. Propylene glycol
      and glycerol are cryoprotectants protecting biological systems from massive ice
      crystallization, since they lower the freezing point of water.

PMID- 25580074
TI  - Alcohol Screening and Brief Intervention as Standard Practice: Working with the
      American Indian/Native Alaskan Populations.
AB  - Alcohol use and the resulting problems associated with high-risk drinking in the
      American Indian/Native Alaskan (AI/NA) population are well-documented, as alcohol
      misuse has taken an incredible toll on many AI/NA communities. Presently, both
      overall health issues and alcohol use occur disproportionately within this
      population. This article provides an updated overview of the impact of alcohol
      use in the United States and within AI/NA communities specifically. It also
      provides recommendations for an alcohol-related screening and brief intervention
      instrument that social workers can begin using in their practice and can be
      utilized within the AI/NA community.

PMID- 25580076
TI  - Patterns in Office Referral Data by Grade, Race/Ethnicity and Gender.
AB  - Research supports that office referral data is useful in informing programmatic
      decisions and in planning interventions such as Positive Behavior Interventions
      and Supports (PBIS). Knowledge of the different patterns of office referrals may
      facilitate the development of interventions that are targeted to specific groups
      of students. This study examines patterns in office referrals within an urban
      district by gender, race/ethnicity and grade. Findings reveal that there are
      clear differences by grade that appear to be related to developmental level, with
      greater numbers of referrals for aggression in younger students (grades K-8),
      greater numbers of referrals for disrespectful behavior in middle school students
      (grades 7-8), and greater numbers of referrals for attendance problems in high
      school students. There were also gender differences in the rate and type of
      referrals, with significantly more referrals for boys' delinquent and aggressive
      behavior than girls, which may relate to how schools define unacceptable behavior
      and the method used to collect this data. Finally, there were differences by
      race/ethnicity, in that there were significantly more referrals for African
      American/black students than Hispanic students, which suggest that schools need
      to consider students' racial/ethnic background in the development of behavioral
      expectations.

PMID- 25580077
TI  - Esophageal cancer-related gene 4 at the interface of injury, inflammation,
      infection, and malignancy.
AB  - In humans, esophageal cancer-related gene 4 (ECRG4) is encoded by four exons in
      the c2orf40 locus of chromosome 2. Translation of ECRG4 messenger ribonucleic
      acid produces a 148 amino acid-secreted 17 KDa protein that is then processed to
      14, ten, eight, six, four, and two KDa peptides, depending on the cell in which
      the gene is expressed. As hypermethylation at the c2orf40 locus inhibits ECRG4
      gene expression in many epithelial cancers, several investigators have speculated
      that ECRG4 is a candidate tumor suppressor. Indeed, overexpression of ECRG4
      inhibits cell proliferation in vitro, but it also has a wide range of effects in
      vivo beyond its antitumor activity. ECRG4 overexpression affects apoptosis,
      senescence, cell migration, inflammation, injury, and infection responsiveness.
      ECRG4 activities also depend on its cellular localization, secretion, and post
      translational processing. These cytokine/chemokine-like characteristics argue
      that ECRG4 is not a traditional candidate tumor suppressor gene, as originally
      predicted by its downregulation in cancer. We review how insights into the
      regulation of ECRG4 gene expression, knowledge of its primary structure, and the
      study of its emerging physiological functions come together to support a much
      more complex role for ECRG4 at the interface of inflammation, infection, and
      malignancy.

PMID- 25580079
TI  - Simulation modeling of high-throughput cryopreservation of aquatic germplasm: a
      case study of blue catfish sperm processing.
AB  - Emerging commercial-level technology for aquatic sperm cryopreservation has not
      been modeled by computer simulation. Commercially available software (ARENA,
      Rockwell Automation, Inc. Milwaukee, WI) was applied to simulate high-throughput
      sperm cryopreservation of blue catfish (Ictalurus furcatus) based on existing
      processing capabilities. The goal was to develop a simulation model suitable for
      production planning and decision making. The objectives were to: 1) predict the
      maximum output for 8-hr workday; 2) analyze the bottlenecks within the process,
      and 3) estimate operational costs when run for daily maximum output. High
      throughput cryopreservation was divided into six major steps modeled with time,
      resources and logic structures. The modeled production processed 18 fish and
      produced 1164 +/- 33 (mean +/- SD) 0.5-ml straws containing one billion
      cryopreserved sperm. Two such production lines could support all hybrid catfish
      production in the US and 15 such lines could support the entire channel catfish
      industry if it were to adopt artificial spawning techniques. Evaluations were
      made to improve efficiency, such as increasing scale, optimizing resources, and
      eliminating underutilized equipment. This model can serve as a template for other
      aquatic species and assist decision making in industrial application of aquatic
      germplasm in aquaculture, stock enhancement, conservation, and biomedical model
      fishes.

PMID- 25580078
TI  - [Reliability and Validity of the Turkish Version of the Social Communication
      Scale.]
AB  - : Reliability and validity of the turkish version of the social communication
      scale. OBJECTIVE: The aim of this study was to evaluate the reliability and
      validity of the Turkish version of the Social Communication Scale (SCQ). METHOD:
      Throughout 2010-2011, we evaluated children who were between 18-60 months of age
      in the outpatient clinic who were diagnosed as having autism (n=49) or pervasive
      developmental disorder not otherwise specified (n=18) according to the DMS-IV
      criteria. The control group consisted of 51children with developmental delay (25
      mental retardation, 26 speech delay) and 71 children with typical development in
      the same age group. We used a one way analysis of variance and post-hoc Tukey HSD
      test to compare the SCQ scores of the groups. For the reliability and validity
      analysis the Cronbach alpha, item-total score correlations and test-retest
      correlations were used. Principal components analysis and varimax rotation were
      used to find the factor solutions. Receiver Operator Characteristic (ROC) curves
      were utilised to detect cut-off scores, sensitivity, specificity, and negative
      and positive predictive values. RESULTS: The analysis yielded 3 factors named
      Language, Reciprocal Social Interaction and Stereotypic Behaviors/Restricted
      Areas of Interest. The Cronbach alpha value of the total score was 0.88. The test
      retest correlation was high (r=0.90, p<0.01). The SCQ Total, Language, Reciprocal
      Social Interaction and Stereotypic Behaviors/Restricted Areas of Interest scores
      were significantly different among the groups. The SCQ Total, Reciprocal Social
      Interaction and Stereotypic Behaviors/Restricted Areas of Interest scores were
      highest in the autism spectrum disorders group. The SCQ Language and Stereotypic
      Behaviors/Restricted Areas of Interest scores were not significantly different
      between the developmental delay and the typical development groups. ROC analysis
      indicated that the SCQ Total and Reciprocal Social Interaction scores
      differentiated very well between the autism spectrum and control group (area
      under the curve 0.89 and 0.91) while the Stereotypic Behaviors/Restricted Areas
      of Interest score differentiated less (0.72). Using a cut-off score of 14.5 for
      the SCQ Total score, sensivity was 0.84, specificity was 0.81, positive
      predictive value was 0.82 and negative predictive value was 0.83. Using a cut-off
      score of 7.5 for the SCQ Reciprocal Social Interaction score, sensivity,
      specifity, positive predictive value and negative predictive value were 0.91,
      0.82, 0.83, 0.90, respectively. CONCLUSION: The results indicated that in
      children younger than 60 months of age the SCQ Total score can differentiate
      subjects with autism spectrum disorders from children with developmental delay
      and typically developing controls; however, the Reciprocal Social Interactions
      score was more sensitive and specific. On the other hand, the negative and
      positive predictive values indicated that there was a fair percentage of false
      negatives and positives. Our results showed that, particularly in younger
      children, the Reciprocal Social Interaction items were more specific and were
      more helpful for differentiation of the children with autism spectrum disorders.
      The availability of the SCQ as a shorter and more practical form of the Autism
      Diagnostic Interview, revised in Turkish, is important as both a research and
      clinical tool.

PMID- 25580080
TI  - Optimizing human activity patterns using global sensitivity analysis.
AB  - Implementing realistic activity patterns for a population is crucial for
      modeling, for example, disease spread, supply and demand, and disaster response.
      Using the dynamic activity simulation engine, DASim, we generate schedules for a
      population that capture regular (e.g., working, eating, and sleeping) and
      irregular activities (e.g., shopping or going to the doctor). We use the sample
      entropy (SampEn) statistic to quantify a schedule's regularity for a population.
      We show how to tune an activity's regularity by adjusting SampEn, thereby making
      it possible to realistically design activities when creating a schedule. The
      tuning process sets up a computationally intractable high-dimensional
      optimization problem. To reduce the computational demand, we use Bayesian
      Gaussian process regression to compute global sensitivity indices and identify
      the parameters that have the greatest effect on the variance of SampEn. We use
      the harmony search (HS) global optimization algorithm to locate global optima.
      Our results show that HS combined with global sensitivity analysis can
      efficiently tune the SampEn statistic with few search iterations. We demonstrate
      how global sensitivity analysis can guide statistical emulation and global
      optimization algorithms to efficiently tune activities and generate realistic
      activity patterns. Though our tuning methods are applied to dynamic activity
      schedule generation, they are general and represent a significant step in the
      direction of automated tuning and optimization of high-dimensional computer
      simulations.

PMID- 25580081
TI  - Kinetics and mechanism of the reaction of hydrogen sulfide with diaquacobinamide
      in aqueous solution.
AB  - We conducted a detailed kinetic study of the reaction of the vitamin B12 analog
      diaquacobinamide ((H2O)2Cbi(III)) with hydrogen sulfide in water from pH 3 to 11.
      The reaction proceeds in three steps: (i) formation of three different complexes
      between cobinamide and hydrogen sulfide, viz. (HO-)(HS-)Cbi(III), (H2O)(HS
      )Cbi(III), and (HS-)2Cbi(III); (ii) inner-sphere electron transfer (ISET) in the
      two complexes with one coordinated HS- to form the reduced cobinamide complex
      [(H)S]Cbi(II); and (iii) addition of a second molecule of hydrogen sulfide to the
      reduced cobinamide. ISET does not proceed in the (HS-)2Cbi(III) complex. The
      final products of the reaction between cobinamide and hydrogen sulfide were found
      to be independent of pH, with the main product being a complex of cobinamide(II)
      with the anion-radical SSH2-.

PMID- 25580082
TI  - Joint Probabilistic Projection of Female and Male Life Expectancy.
AB  - BACKGROUND: The United Nations (UN) produces population projections for all
      countries every two years. These are used by international organizations,
      governments, the private sector and researchers for policy planning, for
      monitoring development goals, as inputs to economic and environmental models, and
      for social and health research. The UN is considering producing fully
      probabilistic population projections, for which joint probabilistic projections
      of future female and male life expectancy at birth are needed. OBJECTIVE: We
      propose a methodology for obtaining joint probabilistic projections of female and
      male life expectancy at birth. METHODS: We first project female life expectancy
      using a one-sex method for probabilistic projection of life expectancy. We then
      project the gap between female and male life expectancy. We propose an
      autoregressive model for the gap in a future time period for a particular
      country, which is a function of female life expectancy and a t-distributed random
      perturbation. This method takes into account mortality data limitations, is
      comparable across countries, and accounts for shocks. We estimate all parameters
      based on life expectancy estimates for 1950-2010. The methods are implemented in
      the bayesLife and bayesPop R packages. RESULTS: We evaluated our model using out
      of-sample projections for the period 1995-2010, and found that our method
      performed better than several possible alternatives. CONCLUSIONS: We find that
      the average gap between female and male life expectancy has been increasing for
      female life expectancy below 75, and decreasing for female life expectancy above
      75. Our projections of the gap are lower than the UN's 2008 projections for most
      countries and so lead to higher projections of male life expectancy.

PMID- 25580083
TI  - Why the racial gap in life expectancy is declining in the United States.
AB  - BACKGROUND: Blacks have lower life expectancy than whites in the United States.
      That disparity could be due to racial differences in the causes of death, with
      blacks being more likely to die of causes that affect the young, or it could be
      due to differences in the average ages of blacks and whites who die of the same
      cause. Prior studies fail to distinguish these two possibilities. OBJECTIVE: In
      this study we determine how much of the 2000-10 reduction in the racial gap in
      life expectancy resulted from narrowing differences in the cause-specific mean
      age at death for blacks and whites, as opposed to changing cause-specific
      probabilities for blacks and whites. METHOD: We introduce a method for separating
      the difference-in-probabilities and difference-inage components of group
      disparities in life expectancy. RESULTS: Based on the new method, we find that
      60% of the decline in the racial gap in life expectancy from 2000 to 2010 was
      attributable to reduction in the age component, largely because of declining
      differences in the age at which blacks and whites die of chronic diseases.
      CONCLUSION: Our findings shed light on the sources of the declining racial gap in
      life expectancy in the United States, and help to identify where advances need to
      be made to achieve the goal of eliminating racial disparities in life expectancy.

PMID- 25580084
TI  - Tissue ischemia microdialysis assessments following severe traumatic haemorrhagic
      shock: lactate/pyruvate ratio as a new resuscitation end point?
AB  - BACKGROUND: Intensive care of severe trauma patients focuses on the treatment of
      haemorrhagic shock. Tissues should be perfused sufficiently with blood and with
      sufficient oxygen content to ensure adequate tissue oxygen delivery. Tissue
      metabolism can be monitored by microdialysis, and the lactate/pyruvate ratio
      (LPR) may be used as a tissue ischemia marker. The aim of this study was to
      determine the adequate cardiac output and haemoglobin levels that avoid tissue
      ischemia. METHODS: Adult patients with serious traumatic haemorrhagic shock were
      enrolled in this prospective observational study. The primary observed parameters
      included haemoglobin, cardiac output, central venous saturation, arterial lactate
      and the tissue lactate/pyruvate ratio. RESULTS: Forty-eight patients were
      analysed. The average age of the patients was 39.8 +/- 16.7, and the average ISS
      was 43.4 +/- 12.2. Hb < 70 g/l was associated with pathologic arterial lactate,
      ScvO2 and LPR. Tissue ischemia (i.e., LPR over 25) developed when CI <= 3.2
      l/min/m(2) and Hb between 70 and 90 g/l were observed. Severe tissue ischemia
      events were recorded when the Hb dropped below 70 g/l and CI was 3.2-4.8
      l/min/m(2). CI >= 4.8 l/min/m(2) was not found to be connected with tissue
      ischemia, even when Hb <= 70 g/l. CONCLUSION: LPR could be a useful marker to
      manage traumatic haemorrhagic shock therapies. In initial traumatic haemorrhagic
      shock treatments, it may be better to maintain CI >= 3.2 l/min/m(2) and Hb >= 70
      g/l to avoid tissue ischemia. LPR could also be a useful transfusion trigger when
      it may demonstrate ischemia onset due to low local DO2 and early reveal low/no
      tissue perfusion.

PMID- 25580085
TI  - Assessment of the feasibility of high-concentration capsaicin patches in the pain
      unit of a tertiary hospital for a population of mixed refractory peripheral
      neuropathic pain syndromes in non-diabetic patients.
AB  - BACKGROUND: High-concentration-capsaicin-patches (Qutenza(r)) have been put on
      the market as a treatment for peripheral neuropathic pain. A minimum
      infrastructure and a determinate skill set for its application are required. Our
      aim was to assess the feasibility of treatment with high-concentration-capsaicin
      patches in clinical practice in a variety of refractory peripheral neuropathic
      pain syndromes in non-diabetic patients. METHODS: Observational, prospective,
      single-center study of patients attended to in the Pain Unit of a tertiary
      hospital, >= 18 year-old non-responders to multimodal analgesia of both genders.
      The feasibility for the application of capsaicin patch in clinical practice was
      evaluated by means of the number of patients controlled per day when this one was
      applied and by means of the times used for patch application. RESULTS: Between
      October 2010 and September 2011, 20 consecutive non-diabetic patients (7 males,
      13 females) with different diagnoses of refractory peripheral neuropathic pain
      syndromes, with a median (range) age of 60 (33-88) years-old were treated with a
      single patch application. The median (range) number of patients monitored per day
      was not modified when the capsaicin patch was applied [27 (26-29)] in comparison
      with it was not applied [28 (26-30)]. The median (range) total time to determine
      and mark the painful area was 9 (6-15) minutes and of patch application was 60
      (58-65) minutes. No important adverse reactions were observed. CONCLUSION: High
      concentration-capsaicin-patch treatment was feasible in our unit for the
      treatment of a population with refractory peripheral neuropathic pain. The
      routine of our unit was not affected by its use.

PMID- 25580087
TI  - Tissue oxygenation as a target for goal-directed therapy in high-risk surgery: a
      pilot study.
AB  - BACKGROUND: Tissue hypoperfusion occurs frequently during surgery and may
      contribute to postoperative organ dysfunction. There is a need for perioperative
      treatment protocols aiming at improving tissue oxygenation (StO2). We
      hypothesised that intra-operative optimisation of StO2 improves tissue perfusion
      and thus reduces postoperative complications. Furthermore, we evaluated the
      feasibility of the optimisation algorithm used. METHODS: We randomized 50 high
      risk patients, all >65 years with ASA physical status III, who underwent major
      abdominal surgery under standardized balanced general anesthesia combined with
      epidural analgesia. Throughout surgery StO2 was monitored at the thenar eminence
      using near-infrared spectroscopy. All patients were treated according to a
      standard care algorithm. In addition, patients in the intervention group were
      treated with dobutamine if necessary to keep or raise StO2 >= 80%. Data were
      recorded continuously and complications were recorded during hospital stay with a
      maximum of 28 days. RESULTS: The number of complications was not significantly
      different between groups (11 vs 20; p = 0.23). Eleven patients in the
      intervention group had no complication, versus 7 in the control group. There was
      no significant difference between groups in length of stay in ICU or in hospital.
      Only ten patients in the intervention group received dobutamine. Administration
      of dobutamine resulted in a moderate 6 [-3 to 10] % increase of StO2. The overall
      protocol adherence was 94%. CONCLUSIONS: No statistically significant difference
      in outcome was realized through intraoperative optimization of StO2 values in
      this pilot study. The protocol used may be considered feasible for clinical
      practice. Further research is obligatory to define both the optimal StO2
      threshold and intervention to treat tissue hypoperfusion. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01342900. Registered 21 April 2011.

PMID- 25580086
TI  - Transversus abdominis-plane block versus local anesthetic wound infiltration in
      lower abdominal surgery: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Postoperative pain management is of great importance in perioperative
      anesthetic care. Transversus abdominis plane (TAP) block has been described as an
      effective technique to reduce postoperative pain and morphine consumption after
      open lower abdominal operations. Meanwhile, local anesthetic infiltration (LAI)
      is also commonly used as a traditional method. However, the effectiveness of
      these two methods has not been compared before. METHODS: A meta-analysis of all
      relevant randomized controlled trials (RCTs) was conducted to compare the
      efficacy of single shot TAP block with that of single shot LAI for postoperative
      analgesia in adults. Major medical databases and trial registries were searched
      for published and unpublished RCTs. The endpoints include postoperative visual
      analog scale (VAS) pain score, morphine requirement, and rate of postoperative
      nausea and vomiting (PONV). For continuous data, weighted mean differences (WMDs)
      were formulated; for dichotomous data, risk ratios (RR) were calculated. Results
      were derived using a random-/fixed-effects model with 95% confidence interval
      (CI). RESULTS: Four RCTs, encompassing 96 TAP-block and 100 LAI patients, were
      included in the final analysis. Patients in the TAP-block group had lower VAS
      pain scores 24 hours postoperatively compared with the LAI group, both at rest
      (WMD [95% CI] = -0.67 [p < 0.01] and with movement (WMD = -0.89, p < 0.01). There
      were no significant between-group differences in 24-hour postoperative morphine
      requirements, the rates if PONV or VAS pain scores at 2 and 4 h postoperatively.
      CONCLUSION: TAP block and LAI provide comparable short-term postoperative
      analgesia, but TAP block has better long-lasting effect.

PMID- 25580088
TI  - Prognosis of critically ill cirrhotic versus non-cirrhotic patients: a
      comprehensive score-matched study.
AB  - BACKGROUND: Cirrhotic patients admitted to an intensive care unit (ICU) have high
      mortality rates. The present study compared the characteristics and outcomes of
      critically ill patients admitted to the ICU with and without cirrhosis using the
      matched Acute Physiology and Chronic Health Evaluation III (APACHE III) and
      Sequential Organ Failure Assessment (SOFA) scores. METHODS: A retrospective case
      control study was performed at the medical ICU of a tertiary-care hospital
      between January 2006 and December 2009. Patients were admitted with life
      threatening complications and were matched for APACHE III and SOFA scores. Of 336
      patients enrolled in the study, 87 in the cirrhosis or noncirrhosis group were
      matched according to the APACHE III scores. Another 55 patients with cirrhosis
      were matched to the 55 patients without cirrhosis according to the SOFA scores.
      Demographic data, aetiology of ICU admission, and laboratory variables were also
      evaluated. RESULTS: The overall hospital mortality rate in the patients with
      cirrhosis in the APACHE III-matched group was more than that in their
      counterparts (73.6% vs 57.5%, P = .026) but the rate did not differ significantly
      in the SOFA-matched group (61.8% vs 67.3%). In the APACHE III-matched group, the
      SOFA scores of patients with cirrhosis were significantly higher than those of
      patients without cirrhosis (P < .001), whereas the difference in APACHE III
      scores was nonsignificant between the SOFA-matched patients with and without
      cirrhosis. CONCLUSIONS: Score-matched analytical data showed that the SOFA scores
      significantly differentiated the patients admitted to the ICU with cirrhosis from
      those without cirrhosis in APACHE III-matched groups, whereas difference in the
      APACHE III scores between the patients with and without cirrhosis were
      nonsignificant in the SOFA-matched group.

PMID- 25580089
TI  - Circulating anti-inflammatory adipokines High Molecular Weight Adiponectin and
      Zinc-alpha2-glycoprotein (ZAG) are inhibited in early sepsis, but increase with
      clinical recovery: a pilot study.
AB  - BACKGROUND: Adipose tissue has been identified as an endocrine organ secreting
      adipokines involved in metabolic and inflammatory pathways. Adiponectin, an anti
      inflammatory adipokine, is reduced in sepsis. High Molecular Weight (HMW)
      adiponectin, the biologically most relevant molecule, has been investigated very
      little in human sepsis. Zinc-alpha2-glycoprotein (ZAG) is a novel adipokine and
      its expression in adipose tissue is positively correlated with adiponectin
      expression. It is not yet known whether ZAG has a role in sepsis. In this study
      we assessed levels of HMW adiponectin and ZAG during different stages of sepsis.
      METHODS: A prospective observational pilot study was carried out on 21 septic
      patients. Serum samples were taken on day 1 and 2 post ICU admission and on day
      of discharge. Samples were analysed for total and HMW adiponectin, HMW/total
      adiponectin ratio, and ZAG. Results were correlated with clinical and metabolic
      data. RESULTS: There were no differences in total adiponectin, HMW adiponectin
      and ZAG plasma concentrations between day 1 (admission) and day 2 of the sepsis
      episode. Compared to admission, a significant increase in total and HMW
      adiponectin and ZAG was observed on the day of discharge when clinical
      improvement had been achieved. There was also an increase in the HMW/total
      adiponectin ratio at that time. CONCLUSIONS: Our data demonstrate an increase in
      both HMW adiponectin and total adiponectin in patients who had clinically
      recovered from sepsis. The increase in HMW/total adiponectin ratio with
      improvement of the clinical condition suggests that HMW adiponectin may have a
      greater role in the inflammatory process and insulin resistance seen in sepsis.
      In this pilot study, we have also demonstrated a significant increase in ZAG in
      critically ill patients temporally related to recovery from sepsis.

PMID- 25580090
TI  - Characteristics, management and outcomes of critically ill patients who are 80
      years and older: a retrospective comparative cohort study.
AB  - BACKGROUND: Older age is associated with chronic illnesses and disability, which
      contribute to increased admission to the intensive care unit (ICU). Our primary
      objective was to compare the characteristics, ICU management and outcomes of
      critically ill patients >= 80 year-old with those of younger patients. METHODS:
      This was a retrospective cohort study of patients admitted to a tertiary-care ICU
      from 1999 to 2011. The characteristics, ICU management and outcomes of patients
      >= 80 year-old were compared with those 50-64.9 and 65-79.9 year-old.
      Multivariate analysis was performed to determine the adjusted risk of Do-Not
      Resuscitate orders and hospital mortality in patients >= 80 year-old compared
      with the younger groups. RESULTS: During the study period, patients aged >= 80
      years (N = 748) represented 7.9% of all ICU admissions and 12.8% of patients aged
      >= 50 years. Chronic cardiac (32.2%) and respiratory (21.8%) diseases were more
      prevalent in them than the younger groups (p < 0.0001). The most common reasons
      for their ICU admission were cardiovascular (30.9%) and respiratory (40.4%)
      conditions. Sepsis was commonly present in them on admission (32.9%). Mechanical
      ventilation and renal replacement therapy were commonly provided (76.9% and
      16.0%, respectively). During ICU stay, Do-Not-Resuscitate orders were more
      frequently written for patients aged >= 80 years (35.0%) compared with 21.9% for
      50-64.9 year-old group, p < 0.0001, and 25.4% for the 60-79.9 year-old group, p <
      0.0001. On multivariate analysis, patients aged >= 80 years were more likely to
      receive these order compared with the 50-64.9 year-old patients (adjusted OR,
      1.83; 95% CI, 1.45-2.31) and the 65-80 year-old patients (adjusted OR, 1.64; 95%
      CI, 1.32-2.04). The hospital mortality increased gradually with age and was
      highest (54.6%) in patients >= 80 year-old (p < 0.0001). Patients >= 80 year-old
      had higher risk of hospital mortality compared with patients aged 50-64.9 years
      (adjusted OR, 2.16; 95% CI, 1.73-2.69) and with those aged 65-79.9 years
      (adjusted OR, 1.51; 95% CI, 1.23-1.86). CONCLUSIONS: Patients >= 80 year-old
      represented a significant proportion of ICU admissions. Although they received
      life sustaining measures similar to younger groups, they had higher adjusted
      mortality risk compared with the younger groups.

PMID- 25580092
TI  - High rates of depressive symptoms among senior high school students preparing for
      national university entrance examination in Turkey.

PMID- 25580091
TI  - High Molecular Weight (HMW): total adiponectin ratio is low in hiv-infected women
      receiving protease inhibitors.
AB  - BACKGROUND: At the time of the study, the HIV-treatment policy in South Africa
      included highly active antiretroviral therapy (HAART) regimens 1 (nucleotide
      reverse transcriptase inhibitors (NRTIs) only), and 2 (protease inhibitors (PI)
      and NRTIs). HAART is associated with the lipodystrophy syndrome, insulin
      resistance and reduced total adiponectin (TA) levels. The high molecular weight
      (HMW):TA ratio is a superior marker of insulin resistance. The aim of this study
      was to establish whether HMW:TA ratios are low in patients on PIs and whether
      they correlate with insulin resistance. METHODS: This was a cross-sectional study
      undertaken in an antiretroviral clinic at a tertiary hospital. The participants
      were 66 HIV-infected females: 22 were on regimen 2 (PI group), 22 on regimen 1
      (non-PI) and 22 treatment naive (TN), matched for BMI and age. Patients with a
      history of diabetes or impaired glucose tolerance were excluded. Serum
      adiponectin multimers were analysed using the AlpcoTM Adiponectin (Multimeric)
      enzyme immunoassay. Waist hip ratios (WHR), glucose and insulin levels were
      assessed, and HOMA-IR and QUICKI calculated. Data were analysed non
      parametrically and multivariate analysis was performed. RESULTS: TA and HMW
      levels were lower in the treatment groups than in the TN group. HMW:TA was lower
      in the PI than in the non-PI and TN groups, and in the non-PI than in the TN
      groups. HMW:TA correlated negatively with waist, insulin and HOMA-IR,
      independently of BMI and duration of therapy. HOMA-IR and QUICKI did not differ
      among the groups. CONCLUSION: HMW:TA is significantly decreased with HAART
      (particularly with PIs, but also with non-PIs) and may be a more sensitive marker
      of insulin resistance in these patients than conventional markers or HMW and
      total adiponectin individually.

PMID- 25580093
TI  - A New Species of Eimeria (Apicomplexa: Eimeriidae) from Green Frog, Lithobates
      clamitans (Anura: Ranidae) from Arkansas, U.S.A.
AB  - Between April and October 2012, 20 juvenile and adult green frogs (Lithobates
      clamitans) were collected by hand or dipnet from 3 counties of Arkansas and
      examined for coccidial parasites. A single frog (5%) was found to be passing
      oocysts of a new eimerian species. Oocysts of Eimeria menaensis n. sp. were
      ellipsoidal to subspheroidal with a bilayered wall and measured (L * W) 25.4 *
      15.6 (23-27 * 13-17) um, with a L/W ratio of 1.6. A micropyle was absent but an
      oocyst residuum and polar granule were present. Sporocysts were spheroidal to
      subspheroidal and measured 5.0 * 5.0 (4-6) um with L/W of 1.1. An indistinct
      Stieda body was present, but sub-and para-Stieda bodies were absent. The
      sporocyst residuum consisted of condensed granules dispersed between sporozoites.
      Sporozoites were elongate and attenuated at both ends with spheroidal anterior
      and posterior refractile bodies. This represents the second report of coccidia
      from L. clamitans and the first time a coccidian has been reported from a green
      frog from Arkansas.

PMID- 25580094
TI  - Confidence Intervals for Random Forests: The Jackknife and the Infinitesimal
      Jackknife.
AB  - We study the variability of predictions made by bagged learners and random
      forests, and show how to estimate standard errors for these methods. Our work
      builds on variance estimates for bagging proposed by Efron (1992, 2013) that are
      based on the jackknife and the infinitesimal jackknife (IJ). In practice, bagged
      predictors are computed using a finite number B of bootstrap replicates, and
      working with a large B can be computationally expensive. Direct applications of
      jackknife and IJ estimators to bagging require B = Theta(n1.5) bootstrap
      replicates to converge, where n is the size of the training set. We propose
      improved versions that only require B = Theta(n) replicates. Moreover, we show
      that the IJ estimator requires 1.7 times less bootstrap replicates than the
      jackknife to achieve a given accuracy. Finally, we study the sampling
      distributions of the jackknife and IJ variance estimates themselves. We
      illustrate our findings with multiple experiments and simulation studies.

PMID- 25580095
TI  - DESIGN, SYNTHESIS, AND EVALUATION OF CARBAZOLE ANALOGS AS POTENTIAL CYTOCHROME
      P450 INHIBITORS.
AB  - Carbazoles are a class of nitrogen-containing aromatic heterocyclic compounds.
      They not only have various biological activities (e.g. antibacterial, anti
      inflammatory, antitumor), but also exhibit useful properties as organic materials
      due to their special structures. Cytochrome P450 enzymes are a superfamily of
      hemoproteins involved in the metabolism of endogenous and exogenous compounds
      including many drugs and environmental chemicals. Some aryl and arylalkyl
      acetylenes, and propargyl ethers have been shown to act as inhibitors of certain
      P450s. In an attempt to improve the potency and selectivity of inhibition, we
      have focused our attention on the design and synthesis of a new series of
      carbazole analogs, a few of which contain a propargyl ether functional group. For
      this project, eight carbazole analogs have been synthesized and characterized.

PMID- 25580096
TI  - Polarizable Mean-Field Model of Water for Biological Simulations with Amber and
      Charmm force fields.
AB  - Although a great number of computational models of water are available today, the
      majority of current biological simulations are done with simple models, such as
      TIP3P and SPC, developed almost thirty years ago and only slightly modified since
      then. The reason is that the non-polarizable force fields that are mostly used to
      describe proteins and other biological molecules are incompatible with more
      sophisticated modern polarizable models of water. The issue is electronic
      polarizability: in liquid state, in protein, and in vacuum the water molecule is
      polarized differently, and therefore has different properties; thus the only way
      to describe all these different media with the same model is to use a polarizable
      water model. However, to be compatible with the force field of the rest of the
      system, e.g. a protein, the latter should be polarizable as well. Here we
      describe a novel model of water that is in effect polarizable, and yet compatible
      with the standard non-polarizable force fields such as AMBER, CHARMM, GROMOS,
      OPLS, etc. Thus the model resolves the outstanding problem of incompatibility.

PMID- 25580098
TI  - Survey of Primary-Care Providers on Perceived Benefits of and Barriers to
      PainTracker.
AB  - Management of chronic pain is a common and complex challenge in primary care.
      Patient-reported outcomes surveys can help assist the patient with chronic pain
      to communicate the symptoms to their provider and engage the patient in treatment
      planning and evaluation to improve both quality of care and patient outcomes. A
      web survey was used to assess clinic providers' perceived ease of use, barriers
      to use, and clinical benefits of a patient-reported outcomes survey, termed
      PainTracker. More than half the respondents were satisfied with PainTracker and
      76% of respondents agreed that PainTracker helps patients participate in their
      pain management. Although only a first step, this study helps evaluate the
      benefits of involving patients in their pain management care.

PMID- 25580099
TI  - DNA Methylation and Colorectal Cancer.
AB  - Colorectal cancer (CRC) is one of the major cancers in the world and second death
      causing cancer in the US. CRC development involves genetic and epigenetic
      alterations. Changes in DNA methylation status are believed to be involved at
      different stages of CRC. Promoter silencing via DNA methylation and
      hypomethylation of oncogenes alter genes' expression, and can be used as a tool
      for the early detection of colonic lesions. DNA methylation use as diagnostic and
      prognostic marker has been described for many cancers including CRC. CpG Islands
      Methylator Phenotype (CIMP) is one of the underlying CRC mechanisms. This review
      aims to define methylation signatures in CRC. The analysis of DNA methylation
      profile in combination with the pathological diagnosis would be useful in
      predicting CRC tumors' evolution and their prognostic behavior.

PMID- 25580097
TI  - Photodynamic therapy: one step ahead with self-assembled nanoparticles.
AB  - Photodynamic therapy (PDT) is a promising treatment modality for cancer with
      possible advantages over current treatment alternatives. It involves combination
      of light and a photosensitizer (PS), which is activated by absorption of specific
      wavelength light and creates local tissue damage through generation of reactive
      oxygen species (ROS) that induce a cascade of cellular and molecular events.
      However, as of today, PDT is still in need of improvement and nanotechnology may
      play a role. PDT frequently employs PS with molecular structures that are highly
      hydrophobic, water insoluble and prone to aggregation. Aggregation of PS leads to
      reduced ROS generation and thus lowers the PDT activity. Some PS such as 5
      aminolevulinic acid (ALA) cannot penetrate through the stratum corneum of the
      skin and systemic administration is not an option due to frequently encountered
      side effects. Therefore PS are often encapsulated or conjugated in/on nano-drug
      delivery vehicles to allow them to be better taken up by cells and to more
      selectively deliver them to tumors or other target tissues. Several nano-drug
      delivery vehicles including liposomes, fullerosomes and nanocells have been
      tested and reviewed. Here we cover non-liposomal self-assembled nanoparticles
      consisting of polymeric micelles including block co-polymers, polymeric micelles,
      dendrimers and porphysomes.

PMID- 25580100
TI  - Secondary Victimization of Abused Mothers by Family Court Mediators.
AB  - Family court often assists divorcing parties in establishing custody
      arrangements. Mediation is commonly used for custody negotiation; however, its
      applicability for cases involving intimate partner abuse (IPA) is debated. This
      study was designed to gain an in-depth understanding of abused mothers' court
      mediation experiences and how those experiences impact future court help-seeking
      when the fathers of their children have been abusive to them. Most women
      experienced secondary victimization during mediation, which had a negative impact
      on their willingness to use the court in the future. Policy recommendations
      include screening for IPA, providing separate mediation sessions, and improving
      court mediators' training.

PMID- 25580101
TI  - Patterns of Emotional Social Support and Negative Interactions among African
      American and Black Caribbean Extended Families.

PMID- 25580102
TI  - Latency Period until the Development of Thyroid Cancer in Young Patients
      Submitted to Radiotherapy: Report of 10 Cases.
AB  - BACKGROUND: Radiotherapy increases the risk of thyroid cancer (TC); patients
      submitted to this treatment should undergo a long-term follow-up. Our aim is to
      describe the features and outcomes of young patients who developed TC after
      radiotherapy. METHODS: At our center, patients undergoing radiotherapy directly
      or indirectly involving the thyroid are regularly followed up in order to detect
      early dysfunction or nodules. Herein, we report the cases of 10 patients who were
      submitted to radiotherapy and developed TC. CLINICAL FINDINGS: Seven patients
      were irradiated in the neck and 3 in nearby regions. The mean age at the last
      radiotherapy session was 10 +/- 5.5 years. The average time until the appearance
      of the first thyroid nodule was 14 +/- 4.7 years. The mean size increment of the
      nodules was 2.4 +/- 1.6 mm/year. On the first cytology, only 2 results were
      suspicious of papillary thyroid cancer (PTC). All patients presented a histology
      of PTC. Eight were in stage I and 2 in stage II. The median follow-up from
      primary diagnosis to TC and beyond was 20 and 3 years, respectively. CONCLUSIONS:
      In these patients, cytologies may be difficult to interpret due to persistent
      benign results. The threshold for surgical indication may be anticipated,
      considering the increased risk of TC. We report the evolution of these nodules
      over time, from the end of primary oncological treatment.

PMID- 25580103
TI  - Primary neuroendocrine tumor of the testis and osseous, cardiac, and lymph node
      metastases in a young patient.
AB  - A 19-year-old patient was diagnosed with a neuroendocrine tumor (NET) of the
      testis and suffered from testicular pain and swelling after orchiectomy. After a
      comprehensive diagnosis, this tumor was shown to be a primary, metastasizing NET
      of the testis. Primary NETs of the testis are very rare; in the literature, only
      approximately 60 patients of all ages are mentioned. Less than 20% of the
      patients show a metastatic spread. In our patient, lymph node, cardiac, and
      osseous metastases have been found. It was possible to remove the lymph node
      metastases through surgery, and the osseous metastases were treated by means of
      radiation. The exploratory thoracotomy revealed a cardiac metastatic spread;
      however, it was so extended that a radical resection was not possible.
      Thereafter, the patient received palliative antiproliferative therapy with the
      somatostatin analogue lanreotide in the form of monthly subcutaneous injections.
      This treatment resulted in a stable disease situation. RESULT: It is possible to
      administer lanreotide autogel in order to control the growth of the tumor in a
      young patient with a metastasizing primary NET of the testis with an impossible
      curative resection of the metastases.

PMID- 25580104
TI  - Multifocal adenomatous oncocytic hyperplasia of the parotid gland.
AB  - Multifocal adenomatous oncocytic hyperplasia (MAOH) is a non-neoplastic lesion
      that is classified as oncocytosis. MAOH is a rare entity of the parotid gland and
      accounts for approximately 0.1% of salivary gland lesions. Here, we report a case
      of MAOH of the parotid gland. The patient was a 71-year-old woman who presented
      with discomfort at the left side of her neck. Fine-needle aspiration cytology of
      the parotid gland revealed a loose sheet-like cluster of round to polygonal cells
      with granular cytoplasm against a hemorrhagic background. The cells had round to
      oval, centrally located nuclei with granular chromatin and without distinct
      nucleoli. Histologically, the lesion was formed of many variable-sized nodules,
      comprising oncocyte-like cells with small round nuclei and eosinophilic granular
      cytoplasm that was positive for mitochondrial antibodies. The diagnosis of MAOH
      is difficult to make by cytology alone, because the findings overlap with those
      of other oncocytic lesions. In particular, the cytological findings of MAOH have
      not been sufficiently reported to date. A correlation of cytology and histology
      was expected. 

PMID- 25580105
TI  - The dynamics of murine mammary stem/progenitor cells.
AB  - The stem/progenitor cells in the murine mammary gland are a highly dynamic
      population of cells that are responsible for ductal elongation in puberty,
      homeostasis maintenance in adult, and lobulo-alveolar genesis during pregnancy.
      In recent years understanding the epithelial cell hierarchy within the mammary
      gland is becoming particularly important as these different stem/progenitor cells
      were perceived to be the cells of origin for various subtypes of breast cancer.
      Although significant advances have been made in enrichment and isolation of
      stem/progenitor cells by combinations of antibodies against cell surface proteins
      together with flow cytometry, and in identification of stem/progenitor cells with
      multi-lineage differentiation and self-renewal using mammary fat pad
      reconstitution assay and in vivo genetic labeling technique, a clear
      understanding of how these different stem/progenitors are orchestrated in the
      mammary gland is still lacking. Here we discuss the different in vivo and in
      vitro methods currently available for stem/progenitor identification, their
      associated caveats, and a possible new hierarchy model to reconcile various
      putative stem/progenitor cell populations identified by different research
      groups.

PMID- 25580107
TI  - Freeway travel speed calculation model based on ETC transaction data.
AB  - Real-time traffic flow operation condition of freeway gradually becomes the
      critical information for the freeway users and managers. In fact, electronic toll
      collection (ETC) transaction data effectively records operational information of
      vehicles on freeway, which provides a new method to estimate the travel speed of
      freeway. First, the paper analyzed the structure of ETC transaction data and
      presented the data preprocess procedure. Then, a dual-level travel speed
      calculation model was established under different levels of sample sizes. In
      order to ensure a sufficient sample size, ETC data of different enter-leave toll
      plazas pairs which contain more than one road segment were used to calculate the
      travel speed of every road segment. The reduction coefficient alpha and reliable
      weight theta for sample vehicle speed were introduced in the model. Finally, the
      model was verified by the special designed field experiments which were conducted
      on several freeways in Beijing at different time periods. The experiments results
      demonstrated that the average relative error was about 6.5% which means that the
      freeway travel speed could be estimated by the proposed model accurately. The
      proposed model is helpful to promote the level of the freeway operation
      monitoring and the freeway management, as well as to provide useful information
      for the freeway travelers. 

PMID- 25580108
TI  - Game theory model of traffic participants within amber time at signalized
      intersection.
AB  - The traffic light scheme is composed of red, green, and amber lights, and it has
      been defined clearly for the traffic access of red and green lights; however, the
      definition of that for the amber light is indistinct, which leads to the
      appearance of uncertainty factors and serious traffic conflicts during the amber
      light. At present, the traffic administrations are faced with the decision of
      whether to forbid passing or not during the amber light in the cities of China.
      On one hand, it will go against the purpose of setting amber lights if forbidding
      passing; on the other hand, it may lead to a mess of traffic flow running if not.
      And meanwhile the drivers are faced with the decision of passing the intersection
      or stopping during the amber light as well. So the decision-making behavior of
      traffic administrations and drivers can be converted into a double game model.
      And through quantification of their earnings in different choice conditions, the
      optimum decision-making plan under specific conditions could be solved via the
      Nash equilibrium solution concept. Thus the results will provide a basis for the
      formulation of the traffic management strategy. 

PMID- 25580109
TI  - Expression of maspin and ezrin proteins in periocular Basal cell carcinoma.
AB  - Background. The aim of this study was to investigate maspin and ezrin expression
      in different subtypes of periocular basal cell carcinoma (BCC). Methods. Tissue
      samples from 43 patients with periocular BCC. Our cases were comprised of 10
      morpheaform, 25 nodular, and 8 adenoid type BCCs. Immunohistochemical staining
      for maspin and ezrin was performed by Envision detection system. Results. There
      was no difference between different subtypes of BCC in maspin expression
      regarding positivity, intensity, and pattern of expression. Ezrin was expressed
      in all subtypes of BCC but the intensity was significantly higher in morpheaform
      BCC compared to nodular and adenoid types (P < 0.001 and P = 0.012, resp.);
      ninety percent of morpheaform samples showed strong ezrin intensity, while this
      strong intensity was only present in 25% and 12% of adenoid and nodular subtypes,
      respectively. There was no correlation between age, sex, or tumor margin
      involvement and expression of neither maspin nor ezrin. There was no correlation
      between maspin and ezrin expression except in nodular type, in which an inverse
      correlation was found (P = 0.004). Conclusion. Ezrin is expressed intensely in
      morpheaform BCC of periocular region. Further studies are needed to show the
      significance of this finding in prognosis of morpheaform BCC. 

PMID- 25580106
TI  - Functional implications of mitochondrial reactive oxygen species generated by
      oncogenic viruses.
AB  - Between 15-20% of human cancers are associated with infection by oncogenic
      viruses. Oncogenic viruses, including HPV, HBV, HCV and HTLV-1, target
      mitochondria to influence cell proliferation and survival. Oncogenic viral gene
      products also trigger the production of reactive oxygen species which can elicit
      oxidative DNA damage and potentiate oncogenic host signaling pathways. Viral
      oncogenes may also subvert mitochondria quality control mechanisms such as
      mitophagy and metabolic adaptation pathways to promote virus replication. Here,
      we will review recent progress on viral regulation of mitophagy and metabolic
      adaptation and their roles in viral oncogenesis.

PMID- 25580110
TI  - Laparoscopic Appendectomy versus Mini-Incision Appendectomy in Patients with
      Lower Body Mass Index and Noncomplicated Appendicitis.
AB  - Laparoscopic appendectomy has become favored over open surgical methods for its
      association with decreased postoperative pain, more rapid return to daily
      activities, and improved cosmetic results. Mini-incision appendectomy was being
      performed in our clinic for a long time especially in patients with
      noncomplicated appendicitis and in patients with appropriate body mass index.
      Although laparoscopy presents obvious advantages especially for obese patients
      and young women, with respect to the results of our study, mini-incision
      appendectomy seems to be an alternative for selected patient groups. 

PMID- 25580111
TI  - The Effectiveness of Self-Expandable Metallic Stent Insertion in Treating Right
      Sided Colonic Obstruction: A Comparison between SEMS and Decompression Tube
      Placement and an Investigation of the Safety and Difficulties of SEMS Insertion
      in Right Colons.
AB  - Objectives. Self-expandable metallic stent (SEMS) is widely used to treat
      malignant colonic obstruction. However, most reports about SEMS insertion have
      concentrated on the left colon. This study aimed to (1) investigate the
      effectiveness of SEMS insertion compared with conventional decompression tube for
      right-sided colonic obstruction and (2) compare the safety and technical success
      of SEMS insertion between left- and right-sided colonic obstructions. Methods.
      The data from thirty-seven patients who underwent SEMS or conventional
      decompression tube placement for malignant colonic obstruction in our hospital
      were analyzed retrospectively. Technical and clinical success, complications, and
      technical difficulties were analyzed. We compared the results between SEMS
      insertion and decompression tube placement in right colons and the outcomes of
      SEMS insertion between right- and left-sided colonic obstructions. Results. For
      right colons, the clinical success rate of SEMS insertion (100%) was
      significantly higher than that of decompression tube placement (55.9%).
      Concerning SEMS insertion, the technical difficulty and safety of SEMS insertion
      were similar between right- and left-sided colonic obstructions. Conclusion. SEMS
      insertion for right-sided colon is significantly more effective than conventional
      decompression tube placement, and this procedure was safer and less technically
      challenging than expected. SEMS insertion should be considered for treating right
      sided malignant colonic obstruction. 

PMID- 25580112
TI  - Accumulation of Bile in the Gallbladder: Evaluation by means of Serial Dynamic
      Contrast-Enhanced Magnetic Resonance Cholangiography with Gadolinium Ethoxybenzyl
      Diethylenetriaminepentaacetic Acid.
AB  - The aim of this study was to evaluate the process of biliary excretion of
      gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) into the
      biliary tract and to assess the accumulation patterns in the gallbladder using MR
      cholangiography obtained with Gd-EOB-DTPA which is a liver-specific hepatobiliary
      contrast agent. Seventy-five patients underwent Gd-EOB-DTPA enhanced MR imaging.
      Serial multiphasic hepatobiliary phase imaging was qualitatively reviewed to
      evaluate the process of the biliary excretion of contrast agent into the bile
      duct and the gallbladder. The accumulation pattern of contrast agent into
      gallbladder was classified into two groups (group 1 = orthodromic type and group
      2 = delayed type). Furthermore, the results in differences of the presence of T1
      hyperintense bile or sludge of gallbladder, gall stones, wall thickening of
      gallbladder, chronic liver disease, and liver cirrhosis between two groups were
      compared. Forty-eight of 75 patients (64%) were included in group 1, and
      remaining 27 (36%) were in group 2. The frequency of the presence of T1
      hyperintense bile or sludge of gallbladder was significantly higher in patients
      with group 2 than that in patients with group 1 (P = 0.041). MR cholangiography
      obtained with Gd-EOB-DTPA showed that there may be an association between the
      biliary accumulation pattern in the gallbladder and the pathological condition. 

PMID- 25580113
TI  - Rab27b is a potential predictor for metastasis and prognosis in colorectal
      cancer.
AB  - Objective. Rab27b is reported to correlate with cancer development and
      progression. However, the association between Rab27b expression and the clinical
      characteristics of colorectal cancer (CRC) is barely investigated. Methods. One
      step quantitative reverse transcription-polymerase chain reaction (qPCR) test
      with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 113
      CRC cases were performed to explore the relationship between Rab27b expression
      and the clinicopathological features of CRC. Cox regression and Kaplan-Meier
      survival analyses were executed to evaluate the prognosis of CRC. Results. The
      results demonstrated that the expression levels of Rab27b mRNA and protein were
      significantly higher in CRC tissues than that in matched noncancerous tissues (P
      < 0.05). Rab27b protein expression in CRC was statistically correlated with serum
      CEA level (P = 0.004), lymph node metastasis (P = 0.001), distant metastasis (P =
      0.009), and TNM stage (P = 0.001). Cox multifactor analysis and Kaplan-Meier
      method suggested that higher Rab27b protein expression (P = 0.041) and tumor
      differentiation (P = 0.001) were significantly associated with the overall
      survival of CRC patients. Conclusions. The data indicated that higher expression
      of Rab27b was observed in CRC tissues and Rab27b may be identified as a useful
      predictor of metastasis and prognosis for CRC. 

PMID- 25580115
TI  - Comment on "simulation-based mastery learning with deliberate practice improves
      clinical performance in spinal anesthesia".

PMID- 25580114
TI  - Hemorrhagic complications of paracentesis: a systematic review of the literature.
AB  - Introduction. Large volume paracentesis is considered a safe procedure carrying
      minimal risk of complications and rarely causing morbidity or mortality. The most
      common complications of the procedure are ascitic fluid leakage, hemorrhage,
      infection, and perforation. The purpose of this study was to evaluate all
      hemorrhagic complications and their outcomes and to identify any common
      variables. Methods. A literature search for all reported hemorrhagic
      complications following paracentesis was conducted. A total of 61 patients were
      identified. Data of interest were extracted and analyzed. The primary outcome of
      the study was 30-day mortality, with secondary endpoints being achievement of
      hemostasis after intervention and mortality based on type of intervention.
      Results. 90% of the patients undergoing paracentesis had underlying cirrhosis.
      Three types of hemorrhagic complications were identified: abdominal wall
      hematomas (52%), hemoperitoneum (41%), and pseudoaneurysm (7%). Forty percent of
      the patients underwent either a surgical (35%) or an IR guided intervention
      (65%). Patients undergoing a surgical intervention had a significantly higher
      rate of mortality at day 30 compared to those undergoing IR intervention.
      Conclusion. Abdominal wall hematomas and hemoperitoneum are the most common
      hemorrhagic complications of paracentesis. Transcatheter coiling and embolization
      appear to be superior to both open and laparoscopic surgery in treatment of these
      complications. 

PMID- 25580116
TI  - Variability modeling of rainfall, deforestation, and incidence of american
      tegumentary leishmaniasis in oran, Argentina, 1985-2007.
AB  - American tegumentary leishmaniasis (ATL) is a disease transmitted to humans by
      the female sandflies of the genus Lutzomyia. Several factors are involved in the
      disease transmission cycle. In this work only rainfall and deforestation were
      considered to assess the variability in the incidence of ATL. In order to reach
      this goal, monthly recorded data of the incidence of ATL in Oran, Salta,
      Argentina, were used, in the period 1985-2007. The square root of the relative
      incidence of ATL and the corresponding variance were formulated as time series,
      and these data were smoothed by moving averages of 12 and 24 months,
      respectively. The same procedure was applied to the rainfall data. Typical
      months, which are April, August, and December, were found and allowed us to
      describe the dynamical behavior of ATL outbreaks. These results were tested at
      95% confidence level. We concluded that the variability of rainfall would not be
      enough to justify the epidemic outbreaks of ATL in the period 1997-2000, but it
      consistently explains the situation observed in the years 2002 and 2004.
      Deforestation activities occurred in this region could explain epidemic peaks
      observed in both years and also during the entire time of observation except in
      2005-2007. 

PMID- 25580117
TI  - Effect of Ultraviolet-A (UV-A) and Ultraviolet-C (UV-C) Light on Mechanical
      Properties of Oyster Mushrooms during Growth.
AB  - This study investigated the effects of ultraviolet-A (UV-A) and ultraviolet-C (UV
      C) light on the mechanical properties in oyster mushrooms during the growth.
      Experiments were carried out with irradiation of the mushrooms with UV-A (365 nm)
      and UV-C (254 nm) light during growth. The exposure time ranged from 10 minutes
      to 60 minutes at intervals of 10 minutes and irradiation was done for three days.
      The samples for experimental studies were cut into cylindrical shapes of diameter
      12.50 mm and thickness 3.00 mm. The storage modulus, loss modulus, and loss
      factor of the irradiated samples and control samples were determined for both UV
      bands and there was a significant difference between the storage modulus, loss
      modulus, and loss factor of the irradiated samples by both UV bands with
      reference to the control sample, P < 0.05. UV-C light irradiated samples had
      higher loss modulus and loss factor but low storage modulus as temperature
      increased from 35 to 100 degrees C with respect to the control sample while UV-A
      light irradiated samples had lower loss modulus, low loss factor, and higher
      storage modulus than UV-C irradiated samples. 

PMID- 25580118
TI  - A framework for prediction of response to HCV therapy using different data mining
      techniques.
AB  - Hepatitis C which is a widely spread disease all over the world is a fatal liver
      disease caused by Hepatitis C Virus (HCV). The only approved therapy is
      interferon plus ribavirin. The number of responders to this treatment is low,
      while its cost is high and side effects are undesirable. Treatment response
      prediction will help in reducing the patients who suffer from the side effects
      and high costs without achieving recovery. The aim of this research is to develop
      a framework which can select the best model to predict HCV patients' response to
      the treatment of HCV from clinical information. The framework contains three
      phases which are preprocessing phase to prepare the data for applying Data Mining
      (DM) techniques, DM phase to apply different DM techniques, and evaluation phase
      to evaluate and compare the performance of the built models and select the best
      model as the recommended one. Different DM techniques had been applied which are
      associative classification, artificial neural network, and decision tree to
      evaluate the framework. The experimental results showed the effectiveness of the
      framework in selecting the best model which is the model built by associative
      classification using histology activity index, fibrosis stage, and alanine amino
      transferase. 

PMID- 25580120
TI  - An In Silico Approach towards the Prediction of Druglikeness Properties of
      Inhibitors of Plasminogen Activator Inhibitor1.
AB  - Diabetic retinopathy is the leading cause of blindness worldwide. It is caused by
      the abnormal growth of the retinal blood vessels. Plasminogen activator
      inhibitor1 (PAI1) is the key growth factor and the inhibition of PAI1 can reduce
      the angiogenesis. In this study, currently available inhibitors are taken and
      tested for the toxicity, binding affinity, and bioactivities of the compounds by
      in silico approach. Five toxic free inhibitors were identified, among which N
      acetyl-D-glucosamine shows the significant binding affinity and two of the
      molecules are having the better bioactivity properties. The molecular
      optimization of 2-(acetylamino)-2-deoxy-A-D-glucopyranose and alpha-L-fucose can
      be used for the treatment of diabetic retinopathy. 

PMID- 25580119
TI  - Alternate Phosphorylation/O-GlcNAc Modification on Human Insulin IRSs: A Road
      towards Impaired Insulin Signaling in Alzheimer and Diabetes.
AB  - Impaired insulin signaling has been thought of as important step in both
      Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). Posttranslational
      modifications (PTMs) regulate functions and interaction of insulin with insulin
      receptors substrates (IRSs) and activate insulin signaling downstream pathways
      via autophosphorylation on several tyrosine (TYR) residues on IRSs. Two important
      insulin receptor substrates 1 and 2 are widely expressed in human, and
      alternative phosphorylation on their serine (Ser) and threonine (Thr) residues
      has been known to block the Tyr phosphorylation of IRSs, thus inhibiting insulin
      signaling and promoting insulin resistance. Like phosphorylation, O-glycosylation
      modification is important PTM and inhibits phosphorylation on same or neighboring
      Ser/Thr residues, often called Yin Yang sites. Both IRS-1 and IRS-2 have been
      shown to be O-glycosylated; however exact sites are not determined yet. In this
      study, by using neuronal network based prediction methods, we found more than 50
      Ser/Thr residues that have potential to be O-glycosylated and may act as possible
      sites as well. Moreover, alternative phosphorylation and O-glycosylation on IRS-1
      Ser-312, 984, 1037, and 1101 may act as possible therapeutic targets to minimize
      the risk of AD and T2DM. 

PMID- 25580122
TI  - Mild Adrenal Steroidogenic Defects and ACTH-Dependent Aldosterone Secretion in
      High Blood Pressure: Preliminary Evidence.
AB  - Introduction. Adrenal glands play a major role in the control of blood pressure
      and mild defects of steroidogenesis and/or inappropriate control of
      mineralocorticoid production have been reported in high blood pressure (HBP).
      Patients and Methods. We used a specific protocol for the evaluation of 100
      consecutive patients with inappropriate or recent onset HBP. Specific methods
      were used to confirm HBP and to diagnose secondary forms of HBP. In addition we
      tested adrenal steroidogenesis with the common cosyntropin test, modified to
      include the simultaneous measurement of renin and aldosterone besides 17
      hydroxyprogesterone (17OHP) and 11-deoxycortisol (S). Results. Secondary forms of
      HBP were diagnosed in 32 patients, including 14 patients with primary
      hyperaldosteronism (PA) (14%) and 10 patients with pheochromocytoma (10%). Mild
      defects of the 21-hydroxylase (21OHD) and 11-hydroxylase (11OHD) enzymes were
      common (42%). ACTH-dependent aldosterone secretion was found in most patients
      (54%) and characteristically in those with mild defects of adrenal
      steroidogenesis (>60%), PA (>75%), and otherwise in patients with apparent
      essential HBP (EHBP) (32%). Discussion. Mild defects of adrenal steroidogenesis
      are common in patients with HBP, occurring in almost half of the patients. In
      those patients as well as in patients with apparent EHBP, aldosterone secretion
      is commonly dependent on ACTH. 

PMID- 25580123
TI  - Long-Term Follow-Up of Patients with 46,XY Partial Gonadal Dysgenesis Reared as
      Males.
AB  - Background/Aims. Studies on 46,XY partial gonadal dysgenesis (PGD) have focused
      on molecular, gonadal, genital, and hormone features; little is known about
      follow-up. Our aim was to analyze long-term outcomes of PGD. Methods.
      Retrospective longitudinal study conducted at a reference service in Brazil. Ten
      patients were first evaluated in the 1990s and followed up until the 2010s;
      follow-up ranged from 13.5 to 19.7 years. All were reared as males and had at
      least one scrotal testis; two bore NR5A1 mutations. Main outcomes were:
      associated conditions, pubertal development, and growth. Results. All patients
      had normal motor development but three presented cognitive impairment; five had
      various associated conditions. At the end of the prepubertal period, FSH was high
      or high-normal in 3/6 patients; LH was normal in all. At the last evaluation, FSH
      was high or high-normal in 8/10; LH was high or high-normal in 5/10; testosterone
      was decreased in one. Final height in nine cases ranged from -1.57 to 0.80 SDS.
      All had spontaneous puberty; only one needed androgen therapy. Conclusions. There
      is good prognosis for growth and spontaneous pubertal development but not for
      fertility. Though additional studies are required, screening for learning
      disabilities is advisable. 

PMID- 25580124
TI  - Maxillary overdentures supported by four splinted direct metal laser sintering
      implants: a 3-year prospective clinical study.
AB  - Purpose. Nowadays, the advancements in direct metal laser sintering (DMLS)
      technology allow the fabrication of titanium dental implants. The aim of this
      study was to evaluate implant survival, complications, and peri-implant marginal
      bone loss of DMLS implants used to support bar-retained maxillary overdentures.
      Materials and Methods. Over a 2-year period, 120 implants were placed in the
      maxilla of 30 patients (18 males, 12 females) to support bar-retained maxillary
      overdentures (ODs). Each OD was supported by 4 implants splinted by a rigid
      cobalt-chrome bar. At each annual follow-up session, clinical and radiographic
      parameters were assessed. The outcome measures were implant failure, biological
      and prosthetic complications, and peri-implant marginal bone loss (distance
      between the implant shoulder and the first visible bone-to-implant contact, DIB).
      Results. The 3-year implant survival rate was 97.4% (implant-based) and 92.9%
      (patient-based). Three implants failed. The incidence of biological complication
      was 3.5% (implant-based) and 7.1% (patient-based). The incidence of prosthetic
      complication was 17.8% (patient-based). No detrimental effects on marginal bone
      level were evidenced. Conclusions. The use of 4 DMLS titanium implants to support
      bar-retained maxillary ODs seems to represent a safe and successful procedure.
      Long-term clinical studies on a larger sample of patients are needed to confirm
      these results. 

PMID- 25580125
TI  - CXCL12 Modulates Prostate Cancer Cell Adhesion by Altering the Levels or
      Activities of beta1-Containing Integrins.
AB  - The mechanisms by which prostate cancer (PCa) cell adhesion and migration are
      controlled during metastasis are not well understood. Here, we studied the effect
      of CXCL12 in PCa cell adhesion and spreading in DU145 and PC3 cell lines using as
      substrates collagen I, fibronectin (FN), and their recombinant fragments. CXCL12
      treatment increased beta1 integrin-dependent PC3 cell adhesion on FN which
      correlated with increased focal adhesion kinase activation. However neither
      alpha5beta1 nor alpha4beta1 subunits were involved in this adhesion. By contrast,
      CXCL12 decreased DU145 adhesion and spreading on FN by downregulating alpha5 and
      beta1 integrin expression. To demonstrate the clinical relevance of CXCL12 in
      PCa, we measured CXCL12 levels in plasma by using ELISA and found that the
      chemokine is elevated in PCa patients when compared to controls. The high
      concentration of CXCL12 in patients suffering from PCa in comparison to those
      with benign disease or healthy individuals implicates CXCL12 as a potential
      biomarker for PCa. In addition these data show that CXCL12 may be crucial in
      controlling PCa cell adhesion on fibronectin and collagen I, possibly via
      crosstalk with integrin receptors and/or altering the expression levels of
      integrin subunits. 

PMID- 25580126
TI  - Persistent Polyclonal B Cell Lymphocytosis B Cells Can Be Activated through CD40
      CD154 Interaction.
AB  - Persistent polyclonal B cell lymphocytosis (PPBL) is a rare disorder, diagnosed
      primarily in adult female smokers and characterized by an expansion of
      CD19(+)CD27(+)IgM(+) memory B cells, by the presence of binucleated lymphocytes,
      and by a moderate elevation of serum IgM. The clinical course is usually benign,
      but it is not known whether or not PPBL might be part of a process leading to the
      emergence of a malignant proliferative disorder. In this study we sought to
      investigate the functional response of B cells from patients with PPBL by use of
      an optimal memory B cell culture model based on the CD40-CD154 interaction. We
      found that the proliferation of PPBL B cells was almost as important as that of B
      cells from normal controls, resulting in high immunoglobulin secretion with in
      vitro isotypic switching. We conclude that the CD40-CD154 activation pathway is
      functional in the memory B cell population of PPBL patients, suggesting that the
      disorder may be due to either a dysfunction of other cells in the
      microenvironment or a possible defect in another B cell activation pathway. 

PMID- 25580127
TI  - Predictors of success of different treatment modalities for management of ectopic
      pregnancy.
AB  - Aim. The purpose of this study was to investigate factors affecting the success
      of different treatment modalities for the management of ectopic pregnancy (EP).
      Methods. One hundred and ninety-seven patients with EP, were included in the
      study. Patients were treated with either intramuscular methotrexate (Mtx) or
      surgical treatment. Results. Mtx was applied in 97 (49.2%) patients. In 67
      patients (69.1%), a single dose of Mtx and in 30 patients (30.9%) a multiple dose
      of Mtx was applied. Forty-seven (70.14%) patients were successfully treated with
      a single-dose Mtx. In the multiple-dose group, the success rate was 70% (21/30
      patients). The difference between the success rates was not statistically
      significant. When the initial serum betahCG value was <1000 mIU/mL, the overall
      success rate of Mtx treatment was determined to be 86.11%; however, the rate
      decreased to 42.3% when the betahCG value was >3000 mIU/mL. On the other hand, if
      the EP mass diameter was <25 mm, the success rate was 89.28% and decreased to
      52.63% when it was >=25 mm. Conclusion. The results of the study showed that
      single-dose treatment with Mtx could be as successful as multiple doses. Overall
      success of Mtx treatment depended on initial betahCG value and EP mass diameter. 

PMID- 25580128
TI  - Malignant pediatric gliosarcoma defies general survival data.
AB  - Gliosarcoma, a variant of glioblastoma multiforme, is a dimorphic tumor known for
      its intra-axial occurrence and poor survival of less than a year. Here is an 11
      year-old boy with gliosarcoma. He had a near total excision and postoperative
      chemoradiotherapy. He has lived through the disease for over 34 months with a
      residual disease.This case report is to report an unusual long survival of
      gliosarcoma in a teenager (Ravisankar et al., 2012). 

PMID- 25580121
TI  - Growth hormone and reproduction: a review of endocrine and autocrine/paracrine
      interactions.
AB  - The somatotropic axis, consisting of growth hormone (GH), hepatic insulin-like
      growth factor I (IGF-I), and assorted releasing factors, regulates growth and
      body composition. Axiomatically, since optimal body composition enhances
      reproductive function, general somatic actions of GH modulate reproductive
      function. A growing body of evidence supports the hypothesis that GH also
      modulates reproduction directly, exerting both gonadotropin-dependent and
      gonadotropin-independent actions in both males and females. Moreover, recent
      studies indicate GH produced within reproductive tissues differs from pituitary
      GH in terms of secretion and action. Accordingly, GH is increasingly used as a
      fertility adjunct in males and females, both humans and nonhumans. This review
      reconsiders reproductive actions of GH in vertebrates in respect to these new
      conceptual developments. 

PMID- 25580129
TI  - A case of systemic lupus erythematosus presenting with an acute abdomen:
      successful treatment with steroid.
AB  - Abdominal pain continues to pose diagnostic challenges for emergency clinicians.
      A 56-year-old Japanese woman was referred to our hospital due to severe abdominal
      pain which presented as occasional epigastric pain five months before and
      intermittent abdominal pain. She had a past history of ileus twice, for both of
      which laparotomy was performed without an alimentary tract resection. The wall
      thickening with marked three-wall structure from terminal ileum to sigmoid colon
      was seen and bladder wall was irregularly thick and enhanced irregularly. Among
      the differential diagnosis of the acute abdomen, autoimmune diseases were
      suspected, especially lupus erythematosus and Henoch-Schonlein purpura. On the
      second day of admission, abdominal pain worsened. The results of examinations of
      antinuclear antibody, anti-double-stranded DNA antibody, ANCA, and the
      complements were not obtained at that time; however, we started 1-g steroid pulse
      treatment for three days with success. With the results obtained later, the
      patient was given a diagnosis of probable systemic lupus erythematosus (SLE). The
      present case shows that SLE can present with acute abdomen and should be included
      in the wide range of the differential diagnosis of acute abdomen. 

PMID- 25580130
TI  - Intrapericardial bronchogenic cyst: an unusual clinical entity.
AB  - Mediastinal cysts are extremely rare clinical disorders. They usually have a
      pericardial origin. In this report, we present a 27-year-old male patient with a
      mediastinal bronchogenic cyst together with clinical presentation and management
      of the pathology. 

PMID- 25580131
TI  - Actinomyces odontolyticus: Rare Etiology for Purulent Pericarditis.
AB  - Purulent pericarditis is one of the most common causes of cardiac tamponade and
      if left untreated has a mortality of 100%. Staphylococcus aureus and
      Streptococcus pneumonia have been implicated as the main etiology of purulent
      pericardial effusion followed by fungi and anaerobic sources. Actinomyces
      odontolyticus pericardial involvement has been reported in the literature only
      once. To our knowledge, this is the first fatal case of A. odontolyticus purulent
      pericarditis in the absence of periodontal disease. 

PMID- 25580132
TI  - Endoscopic stenting and clipping for anastomotic stricture and persistent
      tracheoesophageal fistula after surgical repair of esophageal atresia in an
      infant.
AB  - Anastomotic stricture (AS) and recurrent tracheoesophageal fistula (TEF) are two
      complications of surgical repair of esophageal atresia (EA). Therapeutic
      endoscopic modalities include stenting, tissue glue, and clipping for TEF and
      endoscopic balloon dilation bougienage and stenting for esophageal strictures. We
      report herein a two-month infant with both EA and TEF who benefited from a
      surgical repair for EA, at the third day of life. Two months later he experienced
      deglutition disorders and recurrent chest infections. The esophagogram showed an
      AS and a TEF confirmed with blue methylene test at bronchoscopy. A partially
      covered self-expanding metal type biliary was endoscopically placed. Ten weeks
      later the stent was removed. This allows for easy passage of the endoscope in the
      gastric cavity but a persistent recurrent fistula was noted. Instillation of
      contrast demonstrated a fully dilated stricture but with a persistent TEF. Then
      we proceeded to placement of several endoclips at the fistula site. The
      esophagogram confirmed the TEF was obliterated. At 12 months of follow-up, he was
      asymptomatic. Stenting was effective to alleviate the stricture but failed to
      treat the TEF. At our knowledge this is the second case of successful use of
      endoclips placement to obliterate recurrent TEF after surgical repair of EA in
      children. 

PMID- 25580133
TI  - Successful use of extracorporeal membrane oxygenation for respiratory failure
      caused by mediastinal precursor T lymphoblastic lymphoma.
AB  - Precursor T lymphoblastic lymphoma (T-LBL) often manifests as a mediastinal mass
      sometimes compressing vital structures like vessels or large airways. This case
      was a 40-year-old male who developed T-LBL presenting as respiratory failure
      caused by mediastinal T-LBL. He presented with persistent life threatening
      hypoxia despite tracheal intubation. We successfully managed this respiratory
      failure using venovenous (VV) ECMO. Induction chemotherapy was started after
      stabilizing oxygenation and the mediastinal lesion shrank rapidly. Respiratory
      failure caused by compression of the central airway by tumor is an oncologic
      emergency. VV ECMO may be an effective way to manage this type of respiratory
      failure as a bridge to chemotherapy. 

PMID- 25580134
TI  - Effect of DiD Carbocyanine Dye Labeling on Immunoregulatory Function and
      Differentiation of Mice Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) have been used to treat a variety of degenerative
      disorders. Labeling of MSCs with an appropriate tracer is vital to demonstrate
      the in vivo engraftment and differentiation of transplanted MSCs. DiD is a
      lipophilic fluorescent dye with near infrared emission spectra that makes it
      suitable for in vivo tracing. Therefore, in the present study the consequences of
      DiD labeling on induction of oxidative stress and apoptosis as well as inhibition
      of biological functions of mesenchymal stem cells (MSCs) were investigated. DiD
      labeling did not provoke the production of ROS, induction of apoptosis, or
      inhibition of production of immunosuppressive factors (PGE2 and IL-10) by MSCs.
      In addition, there were no statistical differences between DiD-labeled and
      unlabeled MSCs in suppression of proliferation and cytokine production (IFN-gamma
      and IL-17) by in vitro stimulated splenocytes or improvement of clinical score in
      EAE after in vivo administration. In addition, DiD labeling did not alter the
      differentiation capacity of MSCs. Taken together, DiD can be considered as a safe
      dye for in vivo tracking of MSCs. 

PMID- 25580136
TI  - Prognostic value of glioma cancer stem cell isolation in survival of primary
      glioblastoma patients.
AB  - Cancer stem cells (CSCs) have been reported to be critical in the initiation,
      maintenance, and progression of cancers. The expression of stem cell markers,
      such as podoplanin (PDPN), CD133, and nestin, may have been correlated with
      malignant progression. However, the effects of CSCs and stem cell markers on
      clinical outcomes in cancer patients remain unclear. In this study, we assessed
      the prognostic roles of glioma CSCs (gCSCs) isolation and stem cell markers in
      patients with primary glioblastoma (pGBM). A cohort of 39 patients with pGBM was
      separated into two groups, those positive or negative for gCSCs, and the
      correlation between gCSC and patient survival was evaluated. We observed
      significantly different cumulative survival (P = 0.045) when comparing patients
      positive for gCSCs patients and negative for gCSC. Among the patients positive
      for gCSCs, we observed no significant differences in survival between those whose
      gCSCs were each positive or negative for PDPN, CD133, or nestin. This study
      strongly supports the prognostic value of gCSCs isolation on the survival of
      patients with pGBM. 

PMID- 25580137
TI  - Patterns of brucellosis infection symptoms in azerbaijan: a latent class cluster
      analysis.
AB  - Brucellosis infection is a multisystem disease, with a broad spectrum of
      symptoms. We investigated the existence of clusters of infected patients
      according to their clinical presentation. Using national surveillance data from
      the Electronic-Integrated Disease Surveillance System, we applied a latent class
      cluster (LCC) analysis on symptoms to determine clusters of brucellosis cases. A
      total of 454 cases reported between July 2011 and July 2013 were analyzed. LCC
      identified a two-cluster model and the Vuong-Lo-Mendell-Rubin likelihood ratio
      supported the cluster model. Brucellosis cases in the second cluster (19%)
      reported higher percentages of poly-lymphadenopathy, hepatomegaly, arthritis,
      myositis, and neuritis and changes in liver function tests compared to cases of
      the first cluster. Patients in the second cluster had a severe brucellosis
      disease course and were associated with longer delay in seeking medical
      attention. Moreover, most of them were from Beylagan, a region focused on sheep
      and goat livestock production in south-central Azerbaijan. Patients in cluster 2
      accounted for one-quarter of brucellosis cases and had a more severe clinical
      presentation. Delay in seeking medical care may explain severe illness. Future
      work needs to determine the factors that influence brucellosis case seeking and
      identify brucellosis species, particularly among cases from Beylagan. 

PMID- 25580135
TI  - Concise Review: Mesenchymal Stem Cells Ameliorate Tissue Injury via Secretion of
      Tumor Necrosis Factor-alpha Stimulated Protein/Gene 6.
AB  - Numerous reports have described therapeutic benefits in various disease models
      after administration of the adult stem/progenitor cells from bone marrow or other
      tissues referred to as mesenchymal stem cells/multipotent mesenchymal stromal
      cells (MSCs). They all showed that one of the important effects of MSCs is to act
      against excessive inflammatory responses and repair the damaged tissues. The
      therapeutic benefits of MSCs were initially interpreted by their migration,
      engraftment, and differentiation into target tissues. However, remarkable
      anatomical structural repairs and functional improvements were increasingly
      observed with a small number of or even no MSCs in the injured tissues. This
      suggests that most beneficial effects are largely due to paracrine secretions or
      cell-to-cell contacts that have multiple effects involving modulation of
      inflammatory and immune responses. Currently, the therapeutic benefits of MSCs
      are in part explained by the cells being activated by signals from injured
      tissues to express an anti-inflammatory protein, tumor-necrosis-factor-alpha
      induced protein 6. This important mechanism of action has attracted increasing
      attention, and therefore we conducted this review to summarize the latest
      research. 

PMID- 25580139
TI  - Respiratory review of 2014: asthma.
AB  - Asthma is a chronic inflammatory disease of the airway that comprises a variety
      of etiologies and inflammatory phenotypes. Clinically, there is a wide range of
      patients with varying severities and responses to individual drugs. The
      introduction of inhaled corticosteroid therapy has dramatically changed the
      treatment of asthma. Recent development of new therapies suggests the possibility
      of another breakthrough. These can be categorized as follows: anti-cytokine
      therapies that usually target eosinophilic inflammation, sublingual
      immunotherapy, and bronchial thermoplasty. In this paper, we will review the
      major articles related to asthma treatment that were published in 2013. 

PMID- 25580138
TI  - Elevated dengue virus nonstructural protein 1 serum levels and altered toll-like
      receptor 4 expression, nitric oxide, and tumor necrosis factor alpha production
      in dengue hemorrhagic Fever patients.
AB  - Background. During dengue virus (DV) infection, monocytes produce tumor necrosis
      factor alpha (TNF-alpha) and nitric oxide (NO) which might be critical to
      immunopathogenesis. Since intensity of DV replication may determine clinical
      outcomes, it is important to know the effects of viral nonstructural protein 1
      (NS1) on innate immune parameters of infected patients. The present study
      investigates the relationships between dengue virus nonstructural protein 1 (NS1)
      serum levels and innate immune response (TLR4 expression and TNF-alpha/NO
      production) of DV infected patients presenting different clinical outcomes.
      Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA), TNF
      alpha production by peripheral blood mononuclear cells (PBMCs), and TLR4
      expression on CD14(+) cells from 37 dengue patients and 20 healthy controls.
      Early in infection, increased expression of TLR4 in monocytes of patients with
      dengue fever (DF) was detected compared to patients with dengue hemorrhagic fever
      (DHF). Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum
      levels during the acute febrile phase and a reduced response to TLR4 stimulation
      by LPS (with a reduced TNF-alpha production) when compared to DF patients.
      Conclusions/Significance. During DV infection in humans, some innate immune
      parameters change, depending on the NS1 serum levels, and phase and severity of
      the disease which may contribute to development of different clinical outcomes. 

PMID- 25580140
TI  - Prognostic value of serum growth differentiation factor-15 in patients with
      chronic obstructive pulmonary disease exacerbation.
AB  - BACKGROUND: Information regarding prognostic value of growth differentiation
      factor 15 (GDF-15) and heart-type fatty acid-binding protein (H-FABP) in patients
      with chronic obstructive pulmonary disease (COPD) exacerbation is limited. The
      aim of this study was to investigate whether serum levels of GDF-15 and H-FABP
      predict an adverse outcome for COPD exacerbation. METHODS: Clinical variables,
      including serum GDF-15 and H-FABP levels were compared in prospectively enrolled
      patients with COPD exacerbation that did or did not experience an adverse
      outcome. An adverse outcome included 30-day mortality and need for endotracheal
      intubation or inotropic support. RESULTS: Ninety-seven patients were included and
      allocated into an adverse outcome (n=10) or a control (n=87) group. Frequencies
      of mental change and PaCO2>37 mm Hg were significantly higher in the adverse
      outcome group (mental change: 30% vs. 6%, p=0.034 and PaCO2>37 mm Hg: 80% vs.
      22%, p<0.001, respectively). Serum GDF-15 elevation (>1,600 pg/mL) was more
      common in the adverse outcome group (80% vs. 43%, p=0.041). However, serum H-FABP
      level and frequency of serum H-FABP elevation (>755 pg/mL) did not differ between
      the two groups. Multivariate analysis showed that an elevated serum GDF-15 and
      PaCO2>37 mm Hg were significant predictors of an adverse outcome (odds ratio
      [OR], 25.8; 95% confidence interval [CI], 2.7-243.8; p=0.005 and OR, 11.8; 95%
      CI, 1.2-115.3; p=0.034, respectively). CONCLUSION: Elevated serum GDF-15 level
      and PaCO2>37 mm Hg were found to predict an adverse outcome independently in
      patients with COPD exacerbation, suggesting the possibility that serum GDF-15
      could be used as a prognostic biomarker of COPD exacerbation.

PMID- 25580141
TI  - The effects of bronchoscope diameter on the diagnostic yield of transbronchial
      lung biopsy of peripheral pulmonary nodules.
AB  - BACKGROUND: Transbronchial lung biopsy (TBLB) is a valuable diagnostic tool for
      peripheral pulmonary lesions. The diagnostic yield of TBLB reportedly ranges from
      41%-60%. Many studies demonstrated the various factors that influence the yield
      of TBLB, including size, location, and distance from the carina or pleura.
      However, no study has evaluated the effects of the bronchoscope diameter. We
      evaluated whether the bronchoscope diameter affected the diagnostic yield of
      TBLB. METHODS: We reviewed records from 178 patients who underwent TBLB using
      bronchoscopes of two different diameters (5.7 mm, thick outer diameter, Olympus
      BF-200; 4.9 mm, thin, BF-260). The fluoroscopic guidance rates, yield of TBLB and
      flexible bronchoscopy (FB) were compared between the two groups. Additionally, we
      compared the results of the procedures with respect to diagnosis, distance from
      the pleura, and size of the lesion. RESULTS: The results of fluoroscopic
      guidance, TBLB, and FB yield using thin diameter bronchoscope were significantly
      better than those obtained with a thick diameter bronchoscope (p=0.021, p=0.036,
      and p=0.010, respectively). Particularly, when the distance from the pleura was
      <= 10 mm, success rates for fluoroscopic guidance and FB with thin bronchoscope
      were higher (p=0.013 and p=0.033, respectively), as compared to with thick
      bronchoscope. CONCLUSION: A thinner diameter bronchoscope increased the yield of
      bronchoscopy, and bronchial washing in conjunction with TBLB was useful in the
      diagnosis of peripheral pulmonary nodules.

PMID- 25580142
TI  - Bilateral Ovarian Metastases from ALK Rearranged Non-Small Cell Lung Cancer.
AB  - Anaplastic lymphoma kinase (ALK) rearrangement, is a kind of driver mutation,
      accounts for 3%-5% of non-small cell lung cancer (NSCLC). NSCLC patients
      harboring ALK fusion genes have distinct clinical features and good response to
      ALK inhibitors. Metastasis from lung cancer to the ovary has rarely been known.
      We report a case of a 54-year-old woman with bilateral ovarian metastases from
      ALK rearranged NSCLC. She underwent bilateral salpingo-oophorectomy for ovary
      masses, which were progressed after cytotoxic chemotherapy although primary lung
      mass was decreased. Histopathological examination of the ovary tumor showed
      characteristic adenocarcinoma patterns of the lung and ALK rearrangement. 

PMID- 25580143
TI  - A Case of Organizing Pneumonia Associated with FOLFIRI Chemotherapy.
AB  - The combination chemotherapy of irinotecan with 5-fluorouracil and leucovorin
      (FOLFIRI regimen) was recently proven to be beneficial in patients with advanced
      colorectal cancer. Pulmonary toxicity is very rare in adverse effects of
      irinotecan. No case of organizing pneumonia (also known as bronchiolitis
      obliterans organizing pneumonia) associated with FOLFIRI chemotherapy has been
      reported. We experienced a case of a 62-year-old man who presented persistent dry
      cough and progressive dyspnea after receiving chemotherapy with FOLFIRI regimen.
      After surgical lung biopsy, the patient was diagnosed with FOLFIRI chemotherapy
      induced organizing pneumonia which was successfully treated with steroid therapy.

PMID- 25580144
TI  - Pulmonary cryptococcosis that mimicked rheumatoid nodule in rheumatoid arthritis
      lesion.
AB  - Recently, the incidence of pulmonary cryptococcosis is gradually increasing in
      rheumatoid arthritis (RA) patients. Pulmonary rheumatoid nodules (PRN) are rare
      manifestations of RA. Eighteen months ago, a 65-year old woman was admitted to
      hospital due to multiple nodules (2.5*2.1*2 cm) with cavitations in the right
      lower lobe. She was diagnosed with RA three year ago. She had been taking
      methotrexate, leflunomide, and triamcinolone. A video-assisted thoracoscopic
      surgery biopsy was performed and PRN was diagnosed. However, a newly growing huge
      opacity with cavitation was detected in the same site. Pulmonary cryptococcal
      infection was diagnosed through a transthoracic computed tomograpy guided needle
      biopsy. Cryptococcus antigen was detected in serum but not in cerebrospinal
      fluid. The patient was treated with oral fluconazole which resulted clinical
      improvement and regression of the nodule on a series of radiography. Herein, we
      report the case of pulmonary cryptococcosis occurring in the same location as
      that of the PRN. 

PMID- 25580145
TI  - Systemic Nocardiosis Mimicking Disease Flare-up after Discontinuation of
      Gefitinib in a Patient with EGFR-Mutant Lung Cancer.
AB  - Disease flare-up after discontinuing epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitor (TKI) has been considered as a critical issue in lung
      cancer patients who have experienced radiologic progression after showing initial
      durable response. This is a case of systemic nocardiosis that occurred after
      chronic steroid use for radionecrosis from stereotactic radiosurgery. It was
      initially thought as a disease flare-up after stopping EGFR-TKI. 

PMID- 25580146
TI  - A case of antiphospholipid syndrome refractory to secondary anticoagulating
      prophylaxis after deep vein thrombosis-pulmonary embolism.
AB  - Antiphospholipid syndrome (APS) is an acquired systemic autoimmune disorder
      characterized by a combination of clinical criteria, including vascular
      thrombosis or pregnancy morbidity and elevated antiphospholipid antibody titers.
      It is one of the causes of deep vein thrombosis and pulmonary embolism that can
      be critical due to the mortality risk. Overall recurrence of thromboembolism is
      very low with adequate anticoagulation prophylaxis. The most effective treatment
      to prevent recurrent thrombosis is long-term anticoagulation. We report on a 17
      year-old male with APS, who manifested blue toe syndrome, deep vein thrombosis,
      pulmonary thromboembolism, and cerebral infarction despite adequate long-term
      anticoagulation therapy. 

PMID- 25580147
TI  - Natural antisense transcripts as therapeutic targets.

PMID- 25580148
TI  - Mulberry extracts alleviate abeta 25-35-induced injury and change the gene
      expression profile in PC12 cells.
AB  - Mulberry, which contained high amounts of anthocyanins, has been used in
      traditional Chinese medicine. Mulberry fruit extracts (ME) have demonstrated the
      antioxidant activity and neuroprotection. The study was to investigate the
      neuroprotective efficacy of ME against beta-amyloid 25-35- (Abeta 25-35-) induced
      PC12 cells injury. Cells preincubated with or without ME (200 MUg/mL) for 24 h
      were treated with Abeta 25-35 (20 MUmol/L) for another 24 h. Cell viability was
      assessed by MTT, gene expression profiles were examined by cDNA microarrays, and
      RT-PCR were used to confirm the results of microarray assays. ME pretreatment was
      found to neutralize the cytotoxicity and prevent Abeta 25-35-induced cells
      injury. Analyses of gene expression profile revealed that genes involving cell
      adhesion, peptidase activity, cytokine activity, ion binding activity, and
      angiogenesis regulation were significantly modulated by ME pretreatment. Among
      those genes, Apaf1, Bace2, and Plcb4 were enriched in the "Alzheimer's disease
      reference pathway" and downregulated after ME intervention. RT-PCR results showed
      that ME preincubation could significantly inhibit Abeta 25-35 increased mRNA
      levels of these three genes. Overall, ME pretreatment could substantially
      alleviate PC12 cells injury and downregulate expression of AD-related genes, such
      as Apaf1, Bace2, and Plcb4. This study has a great nutrigenomics interest and
      brings new and important light in the field of AD intervention. 

PMID- 25580150
TI  - Inhibitory Effect of a Hot-Water Extract of Leaves of Japanese Big-Leaf Magnolia
      (Magnolia obovata) on Rotavirus-Induced Diarrhea in Mouse Pups.
AB  - The leaf of Japanese big-leaf magnolia (Magnolia obovata Thunb.) has long been
      used as a natural packaging material for traditional foods in Japan. However,
      many of the physiological functions of the leaves against oral infection and
      resultant illness remain unclear. The aim of the present study was to investigate
      the effects of a hot-water extract of the leaves of Magnolia obovata on diarrhea
      induced by rotavirus (RV), a major cause of acute diarrhea. RV strain SA11 was
      mixed with the M. obovata leaf extract and inoculated orally to neonatal BALB/c
      mouse pups. Simultaneous inoculation of SA11 with the extract significantly
      decreased the incidence of diarrhea. In addition, the extract significantly
      inhibited cytopathic effects and mRNA expression of viral proteins in SA11
      infected MA104 cells. Two flavonoid glycosides, quercitrin and rutin, were
      strongly suggested to be major anti-RV agents in the extract by serial solvent
      extraction and reversed-phase HPLC-ESI-MS analysis. Our results suggest that the
      hot-water extract of M. obovata leaves can be used as a medicine or food additive
      to prevent and ameliorate RV-induced diarrhea in individuals that may have
      difficulty in benefitting from the RV vaccines. 

PMID- 25580149
TI  - KCHO-1, a Novel Antineuroinflammatory Agent, Inhibits Lipopolysaccharide-Induced
      Neuroinflammatory Responses through Nrf2-Mediated Heme Oxygenase-1 Expression in
      Mouse BV2 Microglia Cells.
AB  - The brain is vulnerable to oxidative stress and inflammation that can occur as a
      result of aging or neurodegenerative diseases. Our work has sought to identify
      natural products that regulate heme oxygenase (HO)-1 and to determine their
      mechanism of action in neurodegenerative diseases. KCHO-1 is a novel herbal
      therapeutic containing 30% ethanol (EtOH) extracts from nine plants. In this
      study, we investigated the antineuroinflammatory effects of KCHO-1 in
      lipopolysaccharide- (LPS-) treated mouse BV2 microglia. KCHO-1 inhibited the
      protein expression of inducible nitric oxide synthase (iNOS), iNOS-derived nitric
      oxide (NO), cyclooxygenase- (COX-) 2, and COX-2-derived prostaglandin E2 (PGE2)
      in LPS-stimulated BV2 microglia. It also reduced tumor necrosis factor-alpha (TNF
      alpha), interleukin-1beta (IL-1beta), and IL-6 production. This effect was
      correlated with the suppression of inhibitor of nuclear factor kappa B-alpha
      (IkappaB-alpha) phosphorylation and degradation and nuclear factor kappa B (NF
      kappaB) translocation and DNA binding. Additionally, KCHO-1 upregulated HO-1
      expression by promoting nuclear translocation of nuclear factor E2-related factor
      2 (Nrf2) in mouse BV2 microglia. Tin protoporphyrin (SnPP), an HO activity
      inhibitor, was used to verify the inhibitory effects of KCHO-1 on proinflammatory
      mediators and proteins associated with HO-1 expression. Our data suggest that
      KCHO-1 has therapeutic potential in neurodegenerative diseases caused by
      neuroinflammation. 

PMID- 25580151
TI  - Mechanisms Underlying the Antinociceptive, Antiedematogenic, and Anti
      Inflammatory Activity of the Main Flavonoid from Kalanchoe pinnata.
AB  - Kalanchoe pinnata (KP) is popularly used for treating inflammatory diseases. This
      study investigated the antinociceptive, antiedematogenic, and anti-inflammatory
      potential of the subcutaneous administration of KP flower aqueous extract (KPFE),
      its ethyl acetate (EtOAcF) and butanol (BuOHF) fractions, and the main KP
      flavonoid [quercetin 3-O-alpha-L-arabinopyranosyl (1 -> 2) alpha-L
      rhamnopyranoside] (KPFV) in mice, as well as its possible mechanisms of action.
      KPFE (30-300 mg/kg) and KPFV (1-10 mg/kg) inhibited the acetic acid-induced
      writhing (ID50 = 164.8 and 9.4 mg/kg, resp.). KPFE (300 mg/kg), EtOAcF (12
      mg/kg), BuOHF (15 mg/kg), or KPFV (0.3-3.0 mg/kg) reduced leukocyte migration on
      carrageenan-induced pleurisy (ID50 = 2.0 mg/kg for KPFV). KPFE (3-30 mg/kg) and
      KPFV (0.3-3.0 mg/kg) reduced the croton oil-induced ear edema (ID50 = 4.3 and
      0.76 mg/kg, resp.). KPFE and KPFV reduced the TNF-alpha concentration in the
      pleural exudates on carrageenan-induced pleurisy test. Moreover, KPFV inhibited
      COX-1 (IC50 = 22.1 MUg/mL) and COX-2 (IC50 > 50 MUg/mL). The selectivity index
      (COX-1IC50 /COX-2IC50 ) was <0.44. These results indicate that KPFE and KPFV
      produced antinociceptive, antiedematogenic, and anti-inflammatory activities
      through COX inhibition and TNF-alpha reduction, revealing that the main flavonoid
      in KP flowers and leaves plays an important role in the ethnomedicinal use of the
      plant. 

PMID- 25580152
TI  - Inhibitory Effect on beta -Hexosaminidase Release from RBL-2H3 Cells of Extracts
      and Some Pure Constituents of Benchalokawichian, a Thai Herbal Remedy, Used for
      Allergic Disorders.
AB  - Introduction. Benchalokawichian (BCW), a Thai traditional herbal formulation, has
      long been used as antipyretic and to treat skin disorders. It comprises roots
      from five herbs: Ficus racemosa, Capparis micracantha, Clerodendrum petasites,
      Harrisonia perforata, and Tiliacora triandra. This polyherbal remedy has recently
      been included in the Thailand National List of Essential Medicines (Herbal
      Products list). Methodology. A Bioassay-guided fractionation technique was used
      to evaluate antiallergy activities of crude extracts, and those obtained by the
      multistep column chromatography isolation of pure compounds. Inhibitory effect on
      the release of beta-hexosaminidase from RBL-2H3 cells was used to determine
      antiallergic activity. Results. Two pure compounds from BCW formulation showed
      higher antiallergic activity than crude or semipure extracts. Pectolinarigenin
      showed the highest antiallergic activity, followed by O-methylalloptaeroxylin,
      with IC50 values of 6.3 MUg/mL and 14.16 MUg/mL, respectively. Moreover, the
      highest activities of pure compounds were significantly higher than
      chlorpheniramine (16.2 MUg/mL). Conclusions. This study provides some support for
      the use of BCW in reducing itching and treatment of other skin allergic
      disorders. The two isolated constituents exhibited high antiallergic activity and
      it is necessary to determine their mechanism of action. Further phytochemical and
      safety studies of pure compounds are required before development of these as
      antiallergy commercial remedies. 

PMID- 25580153
TI  - Adjustment of trendy, gaming and less assimilated tweens in the United States.
AB  - Youth transitioning from childhood to adolescence (tweens) are exposed to
      increasing amounts of media and advertisement. Tweens have also emerged as a
      major marketing segment for corporate America with increasing buying power.We
      examine how tweens relate to popular culture messages and the association of
      different orientations to popular culture on adjustment. A secondary data
      analysis was conducted on a marketing survey of 3527 tweens, aged 10-14 years,
      obtained from 49 schools using stratified sampling methods. A sample of children
      nationwide described their preferences on popular culture and measures of
      psychosocial adjustment. Using cluster analysis, we identified three main
      clusters or adaptation styles of tweens: (1) those who enjoyed gaming, (2) trendy
      youth and (3) youth less assimilated into popular culture. There were differences
      in clusters based on adjustment indices. Gaming and trendy tweens reported higher
      self-perceptions of being smart, caring and confident compared to less
      assimilated tweens. However, gaming and trendy tweens worried more about fitting
      in than less assimilated tweens. Gaming and trendy tweens also endorsed future
      goals and traditional values more strongly than less assimilated tweens. Trendy
      tweens reported the strongest positive feelings about substance use. Results
      suggest that for each method of adaptation (gamer, trendy and less assimilated),
      there are unique differences in adjustment that can impact the child's future.
      Parents and service providers must recognize the complexity of these decisions
      and be sensitive to the unique needs of youth as they move from childhood to
      adolescence.

PMID- 25580154
TI  - The Old Solutions Are the New Problem: How Do We Better Use What We Already Know
      About Reducing the Burden of Mental Illness?
AB  - Kazdin and Blase (2011) propose that traditional models of delivering therapy
      require more resources than are available to address the scope of mental illness.
      We argue that finding new platforms and avenues for our existing treatments is a
      good start but that it is not enough. We contend that the field also needs to
      develop formal strategies to reorganize its increasing abundance of knowledge to
      address the scarcity of resources for its application. If we can better utilize
      our existing knowledge, treatment delivery and service resource allocation can
      become more efficient and effective. If the field continues with its almost
      singular emphasis on knowledge proliferation (e.g., developing new treatments),
      as opposed to knowledge management (e.g., developing new ways to design, apply,
      and organize existing treatments), the problem outlined by Kazdin and Blase
      cannot be solved. 

PMID- 25580156
TI  - Effect of the polydispersity of RBCs on the recovery rate of RBCs during the
      removal of CPAs.
AB  - In the process of removing cryoprotectants from cryopreserved blood, the
      theoretically optimal operating condition, which is based on the assumption that
      the distribution of red blood cells is uniform, is often used to reduce or even
      avoid the hypotonic damage to cells. However, due to the polydispersity of cells,
      the optimal condition is actually not reliable. In this study, based on the
      discrete concept developed in our previous work, the effect of the polydispersity
      on the recovery rate of cells in the dilution-filtration system was statistically
      investigated by assigning three random parameters, isotonic cell volume, cell
      surface area, and osmotically inactive cell volume, to cells in small units of
      blood. The results show that, due to the polydispersity, the real recovery rate
      deviates from the ideal value that is based on uniform distribution. The
      deviation significantly increases with the standard errors of cell parameters,
      and it can be also magnified by high cryoprotectant concentrations. Under the
      effect of polydispersity, the uniform distribution-based optimized blood or
      diluent flow rate is not perfect. In practice, one should adopt a more
      conservative blood or diluent flow rate so that the hypotonic damage to cells can
      be further reduced. 

PMID- 25580157
TI  - The relationships between short-term exposure to particulate matter and mortality
      in Korea: Impact of particulate matter exposure metrics for sub-daily exposures.
AB  - Most studies of short-term particulate matter (PM) exposure use 24-hour averages.
      However, other pollutants have stronger effects at shorter timeframes, which has
      influenced policy (e.g., ozone 8-hour maximum). Selecting appropriate exposure
      timeframes is important for effective regulation. The U.S. EPA identified health
      effects for sub-daily PM exposures as a critical research need. Unlike most
      areas, Seoul, Korea has hourly measurements of PM10, although not PM2.5. We
      investigated PM10 and mortality (total, cardiovascular, respiratory) in Seoul
      (1999-2009) considering sub-daily exposures: 24-hour, daytime (7am-8pm), morning
      (7-10am), nighttime (8pm-7am), and 1-hour daily maximum. We applied Poisson
      generalized linear modeling adjusting for temporal trends and meteorology. All
      PM10 metrics were significantly associated with total mortality. Compared to
      other exposure timeframes, morning exposure had the most certain effect with
      total mortality (based on statistical significance). A 10ug/m3 increase in 24
      hour, daytime, morning, nighttime, and 1-hour maximum PM10 was associated with a
      0.15% (95% confidence interval 0.02-0.28%), 0.14% (0.01-0.27%), 0.10% (0.03
      0.18%), 0.12% (0.03-0.22%), and 0.10% (0.00-0.21%) increase in total mortality,
      respectively. PM10 was significantly associated with cardiovascular mortality for
      24-hour, morning, and nighttime exposures. We did not identify significant
      associations with respiratory mortality. Results support use of a 24-hour
      averaging time as an appropriate metric for health studies and regulation,
      particularly for PM10 and mortality.

PMID- 25580158
TI  - Onco-STS: a web-based laboratory information management system for sample and
      analysis tracking in oncogenomic experiments.
AB  - BACKGROUND: Whole genomes, whole exomes and transcriptomes of tumour samples are
      sequenced routinely to identify the drivers of cancer. The systematic sequencing
      and analysis of tumour samples, as well other oncogenomic experiments,
      necessitates the tracking of relevant sample information throughout the
      investigative process. These meta-data of the sequencing and analysis procedures
      include information about the samples and projects as well as the sequencing
      centres, platforms, data locations, results locations, alignments, analysis
      specifications and further information relevant to the experiments. RESULTS: The
      current work presents a sample tracking system for oncogenomic studies (Onco-STS)
      to store these data and make them easily accessible to the researchers who work
      with the samples. The system is a web application, which includes a database and
      a front-end web page that allows the remote access, submission and updating of
      the sample data in the database. The web application development programming
      framework Grails was used for the development and implementation of the system.
      CONCLUSIONS: The resulting Onco-STS solution is efficient, secure and easy to use
      and is intended to replace the manual data handling of text records. Onco-STS
      allows simultaneous remote access to the system making collaboration among
      researchers more effective. The system stores both information on the samples in
      oncogenomic studies and details of the analyses conducted on the resulting data.
      Onco-STS is based on open-source software, is easy to develop and can be modified
      according to a research group's needs. Hence it is suitable for laboratories that
      do not require a commercial system.

PMID- 25580155
TI  - Management of conjunctival malignant melanoma: a review and update.
AB  - Conjunctival malignant melanoma is a pigmented lesion of the ocular surface. It
      is an uncommon but potentially devastating tumor that may invade the local
      tissues of the eye, spread systemically through lymphatic drainage and
      hematogenous spread, and recur in spite of treatment. Despite its severity, the
      rarity of available cases has limited the evidence for diagnosis and management.
      This review will provide an overview of the epidemiology, presentation,
      diagnosis, management, and surveillance of conjunctival melanoma, with an
      emphasis on recent advances in biological therapies to treat this disease.

PMID- 25580159
TI  - From single-gene to multiplex analysis in lung cancer, challenges and
      accomplishments: a review of a single institution's experience.
AB  - Molecular selection has led to the successful use of novel tyrosine kinase
      inhibitors (TKIs) in non-small-cell lung cancers (NSCLCs). For instance,
      mutations in EGFR and translocations and fusions in ALK render tumor cells
      sensitive to some TKIs, leading to substantial clinical benefits. Molecular
      testing such as DNA sequencing or fragment analysis following PCR, and evaluation
      of copy number and gene positioning by FISH, have been developed and used
      clinically to identify mutations/fusions. Meanwhile, TKIs to target actionable
      mutations/fusions in several other oncogenes are being evaluated. High-throughput
      sequencing can provide therapy-predictive information as well as identify novel
      targetable genomic alterations. In this article, we report our experience
      enabling single-gene testing, and our evolution to panel-based next-generation
      sequencing.

PMID- 25580160
TI  - Clinical subtypes of chronic traumatic encephalopathy: literature review and
      proposed research diagnostic criteria for traumatic encephalopathy syndrome.
AB  - The long-term consequences of repetitive head impacts have been described since
      the early 20th century. Terms such as punch drunk and dementia pugilistica were
      first used to describe the clinical syndromes experienced by boxers. A more
      generic designation, chronic traumatic encephalopathy (CTE), has been employed
      since the mid-1900s and has been used in recent years to describe a
      neurodegenerative disease found not just in boxers but in American football
      players, other contact sport athletes, military veterans, and others with
      histories of repetitive brain trauma, including concussions and subconcussive
      trauma. This article reviews the literature of the clinical manifestations of CTE
      from 202 published cases. The clinical features include impairments in mood (for
      example, depression and hopelessness), behavior (for example, explosivity and
      violence), cognition (for example, impaired memory, executive functioning,
      attention, and dementia), and, less commonly, motor functioning (for example,
      parkinsonism, ataxia, and dysarthria). We present proposed research criteria for
      traumatic encephalopathy syndrome (TES) which consist of four variants or
      subtypes (TES behavioral/mood variant, TES cognitive variant, TES mixed variant,
      and TES dementia) as well as classifications of 'probable CTE' and 'possible
      CTE'. These proposed criteria are expected to be modified and updated as new
      research findings become available. They are not meant to be used for a clinical
      diagnosis. Rather, they should be viewed as research criteria that can be
      employed in studies of the underlying causes, risk factors, differential
      diagnosis, prevention, and treatment of CTE and related disorders. 

PMID- 25580162
TI  - QuEChERS-based approach toward the analysis of two insecticides, methomyl and
      aldicarb, in blood and brain tissue.
AB  - QuEChERS has been widely utilized for the analysis of pesticides in produce, but
      it has not been as widely used in clinical test specimens, especially for
      smaller, sub-gram sample sizes. This study describes the application of a
      miniaturized QuEChERS methodology toward the analysis of two insecticides,
      methomyl and aldicarb, in guinea pig blood and brain tissue. Matrix effects and
      absolute recoveries were investigated for both analytes in the two matrices.
      While the matrix effects of methomyl in both matrices were minimal at most levels
      (i.e., from -20% to 20%), aldicarb experienced signal suppression under the
      described conditions (mean of -47%). However, the matrix effects were not cause
      for concern due to the sensitivity of the method and the use of matrix-matched
      standards. The precision and accuracy of the method were excellent over a range
      of concentrations that spanned three orders of magnitude. The limits of detection
      (LOD) for both carbamates were determined to be 0.1 ng mL-1 in blood and 0.2 ng g
      1 in brain. Other validation parameters, such as linearity, accuracy, precision,
      and recovery, were also satisfactory in the blood and brain tissue. This method
      was demonstrated to be sensitive and reproducible, and it should be applicable to
      the analysis of a wide range of compounds of interest in sub-gram- and sub
      milliliter-sized clinical and toxicology specimens.

PMID- 25580163
TI  - Aldehyde-functional polycarbonates as reactive platforms.
AB  - Ozonolysis of allyl-functional polycarbonates provides aldehyde-functional
      polycarbonates that have potential to be reactive platforms for transformation
      into diverse active materials.

PMID- 25580161
TI  - Alpha-synuclein biology in Lewy body diseases.
AB  - alpha-Synuclein is an abundantly expressed neuronal protein that is at the center
      of focus in understanding a group of neurodegenerative disorders called alpha
      synucleinopathies, which are characterized by the presence of aggregated alpha
      synuclein intracellularly. Primary alpha-synucleinopathies include Parkinson's
      disease (PD), dementia with Lewy bodies and multiple system atrophy, with alpha
      synuclein also found secondarily in a number of other diseases, including
      Alzheimer's disease. Understanding how alpha-synuclein aggregates form in these
      different disorders is important for the understanding of its pathogenesis in
      Lewy body diseases. PD is the most prevalent of the alpha-synucleinopathies and
      much of the initial research on alpha-synuclein Lewy body pathology was based on
      PD but is also relevant to Lewy bodies in other diseases (dementia with Lewy
      bodies and Alzheimer's disease). Polymorphism and mutation studies of SNCA, the
      gene that encodes alpha-synuclein, provide much evidence for a causal link
      between alpha-synuclein and PD. Among the primary alpha-synucleinopathies,
      multiple system atrophy is unique in that alpha-synuclein deposition occurs in
      oligodendrocytes rather than neurons. It is unclear whether alpha-synuclein
      originates from oligodendrocytes or whether it is transmitted somehow from
      neurons. alpha-Synuclein exists as a natively unfolded monomer in the cytosol,
      but in the presence of lipid membranes it is thought to undergo a conformational
      change to a folded alpha-helical secondary structure that is prone to forming
      dimers and oligomers. Posttranslational modification of alpha-synuclein, such as
      phosphorylation, ubiquitination and nitration, has been widely implicated in
      alpha-synuclein aggregation process and neurotoxicity. Recent studies using
      animal and cell models, as well as autopsy studies of patients with neuron
      transplants, provided compelling evidence for prion-like propagation of alpha
      synuclein. This observation has implications for therapeutic strategies, and much
      recent effort is focused on developing antibodies that target extracellular alpha
      synuclein. 

PMID- 25580164
TI  - Clinical Characteristics and Antimicrobial Susceptibility Pattern of Hospitalized
      Patients with Community Acquired Urinary Tract Infections at a Regional Hospital
      in Taiwan.
AB  - BACKGROUND: Community-acquired urinary tract infection (UTI) is the most common
      bacterial infection encountered at hospitals. Effective empirical antibiotic
      therapy relies on updated epidemiological data. AIM: We described the
      epidemiology of patients with urosepsis presenting to a community hospital in
      Taiwan in order to assess the appropriateness of empirical therapy. METHODS:
      Retrospective cohort study of hospitalized adult patients with UTI from January 1
      to December 31 in 2010. The clinical and microbiological characteristics were
      analyzed using descriptive statistics. Logistic regression analysis was performed
      to determine predictors of antibiotic resistance. FINDINGS: A total of 420
      consecutive patients with 599 isolates were identified. Most patients were >=65
      years old and women (75.4%), and 114 patients (27.1%) had bacteremia. Escherichia
      coli (69%) was the most common organism. Cefazolin was effective against E. coli,
      K. pneumoniae, and P. mirabilis in greater than 80% of the cases. In male
      patients, urinary catheter and renal stone were independent predictors for
      cefazolin resistance; while diabetes mellitus and malignancy were predictors
      among female patients. CONCLUSION: Patients admitted with UTI should be screened
      to identify risk factors for bacteremia and antimicrobial resistance. The
      treatment guideline in Taiwan needs to be revised in the current era of
      increasing antimicrobial resistance.

PMID- 25580166
TI  - Nitric Oxide and Cellular Maturity Are Key Components of Pro-Inflammatory
      Cytokine-Induced Apoptosis of Human Fetal Lung Epithelial Cells.
AB  - Inflammation is a major contributor to the pathogenesis of bronchopulmonary
      dysplasia (BPD). BPD is associated with prematurity of birth, sepsis, with
      increased production of both cytokines and nitric oxide, and with the shedding of
      bronchial epithelial cells. The pathological mechanisms involved in this disease
      remain unclear, in particular the role that epithelial maturity plays. The
      effects of pro-inflammatory cytokines upon immature and mature cells are examined
      within this study, using primary culture of human lung epithelial cells. Pro
      inflammatory cytokines increase inducible nitric oxide synthase (iNOS) expression
      and raise NO production, irrespective of cellular maturity. Pre-incubation with
      1400W, a specific iNOS inhibitor, abrogated pro-inflammatory cytokine-induced NO
      generation and apoptosis. However, immature fetal lung epithelial cells were
      uniquely sensitive to cellular injury in response to cytokine exposure. These
      observations suggest that pro-inflammatory cytokines, which are present within
      BPD, may cause apoptosis of lung epithelial cells via de novo generation of NO.
      Furthermore, the prematurity of lung epithelial cells may be a factor in free
      radical mediated pulmonary damage.

PMID- 25580165
TI  - Bone Physiology, Biomaterial and the Effect of Mechanical/Physical
      Microenvironment on MSC Osteogenesis: A Tribute to Shu Chien's 80th Birthday.
AB  - Professor Shu Chien is a world-renowned leader and founder of Bioengineering. In
      particular, he has made seminal contributions to advancing our systematic and
      insightful understanding of how cells perceive their physical/mechanical
      environment and coordinate cellular functions. In this review, as part of a
      tribute to Prof. Shu Chien's scientific achievement, we summarize the research
      progress in understanding the physiology of bone cells interacting with different
      mechanical/physical environments during bone tissue regeneration/repair. We first
      introduce the cellular composition of the bone tissue and the mechanism of the
      physiological bone regeneration/repair process. We then describe the properties
      and development of biomaterials for bone tissue engineering, followed by the
      highlighting of research progresses on the cellular response to mechanical
      environmental cues. Finally, several latest advancements in bone tissue
      regeneration and remaining challenges in the field are discussed for future
      research directions.

PMID- 25580167
TI  - Impact of pharmaceutical counseling in minor health problems in rural Portugal.
AB  - OBJECTIVES: The objectives of this study were to determine the prevalence of self
      medication and to evaluate the clinical impact of pharmaceutical counseling.
      METHODS: A cross-sectional study was used with a prospective component, the
      latter to evaluate the impact of pharmaceutical counseling. The study was
      conducted in a rural community pharmacy for 14 consecutive days in December 2012,
      recruiting all individuals who agreed to participate and met the eligibility
      criteria. During a face-to-face direct interview demographic and clinical
      characteristics of patients were registered, followed by a pharmaceutical
      intervention, which consisted of evaluating the symptoms, selecting the most
      appropriate non-prescription medicine (NPM) available and advising the patient on
      pharmacologic and non-pharmacologic measures, all according to established
      protocols for minor health problems. When appropriate, the patient was referred
      to a medical appointment. One week later, the clinical outcome of such
      intervention was measured by asking the patients about the resolution of their
      minor health problems. RESULTS: Data from 298 patients were analyzed, the
      majority being female (60.1%) with an average age of 44.84 years (SD=22.41).
      Respiratory problems were the most frequent (n=78; 26.2%) and respiratory tract
      medication was the most frequently indicated (n= 77; 27.8%). The observed
      prevalence of self-medication was 40.7%. Of the 271 patients' beneficiaries of
      pharmaceutical counseling, 86.8% had their minor health problems solved after one
      week (ranging from 77.5% to 88.2% according to a sensibility analysis for drop
      outs). CONCLUSIONS: This work is important as it demonstrates the beneficial
      impact of pharmaceutical counseling, a very relevant area for the pharmacist and
      where literature is particularly scarce.

PMID- 25580168
TI  - Validation of the parental knowledge and attitude towards antibiotic usage and
      resistance among children in Tetovo, the Republic of Macedonia.
AB  - OBJECTIVE: This study sought to explore the knowledge and attitudes of parents on
      the use of antibiotics among children that could serve as baseline data and
      provide further insight in planning and developing strategies for local health
      education purposes. METHODS: A cross-sectional survey involving 500 parents who
      attended community pharmacies in Tetovo, Republic of Macedonia, was conducted
      using a self-administered questionnaire from October 2013 to January 2014. The
      questionnaire included demographics, knowledge and attitude statements of parents
      towards antibiotics. The data collected were analyzed using SPSS program, version
      19.0. Descriptive statistics was used to summarize the data. In all statistical
      analyses, a p-value of <0.05 was considered statistically significant. RESULTS:
      Nearly 40% of the parents demonstrated a moderate level of knowledge. The highest
      correct response in the knowledge part was the awareness of parents in using
      antibiotics to treat a bacterial infection (61.2%). However, most of the parents
      did not know that antibiotics cannot cure viral infections (59.6%). About 48.2%
      of the parents were aware of the antibiotic resistance as s result of the
      overuse. Concerning attitudes, 60.8% reported keeping any leftover antibiotics,
      77.0% agreed that taking antibiotics when having cold symptoms could help their
      children recover faster, while, 74.6% wrongly agreed with the statement of
      appropriate use of antibiotics for prophylaxis' measure. CONCLUSIONS: This study
      has documented the main areas that merit attention when parental knowledge on
      antibiotic use for their children is the concern, reflecting in some
      inappropriate attitudes as well. The findings highlight the need to devise
      effective interventions to decrease misconceptions regarding antibiotic use and
      to increase parents' awareness for the risks of inappropriate use of antibiotics
      in children specifically and in the community at large.

PMID- 25580169
TI  - Exploring consumer understanding and preferences for pharmacy quality
      information.
AB  - OBJECTIVE: To describe consumer understanding of pharmacy quality measures and
      consumer preferences for pharmacy quality information. METHODS: Semi-structured
      focus group design was combined with survey methods. Adults who filled
      prescription medications for self-reported chronic illnesses at community
      pharmacies discussed their understanding of Pharmacy Quality Alliance approved
      quality measures. Questions examined preference of pharmacy quality information
      rating systems (e.g. stars versus percentages) and desired data display/formats.
      During the focus group, participants completed a survey examining their
      understanding of each pharmacy quality measure. All focus group discussions were
      transcribed verbatim. Data were analyzed using thematic analysis and descriptive
      statistics. RESULTS: Thirty-four individuals participated (mean age= 62.85;
      SD=16.05). Participants were unfamiliar with quality measures information and
      their level of understanding differed for each quality measure. Surveys indicated
      94.1% understood "Drug-Drug Interactions" and "Helping Patients Get Needed
      Medications" better than other measures (e.g., 76.5% understood "Suboptimal
      Treatment of Hypertension in Patients with Diabetes"). Qualitative analysis
      indicated participants preferred an overall pharmacy rating for quick access and
      use. However, participants also wanted quality measures information displayed by
      health conditions. Participants favored comparison of their pharmacy to city data
      instead of state data. Most participants liked star ratings better than
      percentages, letter grades, or numerical ratings. CONCLUSIONS: Individuals who
      have a chronic illness and regularly use community pharmacies are interested in
      pharmacy quality measures. However, specific quality measures were not understood
      by some participants. Participants had specific preferences for the display of
      pharmacy quality information which will be helpful in the design of appropriate
      quality report systems.

PMID- 25580170
TI  - Health care professionals' perspectives on automated multi-dose drug dispensing.
AB  - BACKGROUND: During the 1980s, manual repackaging of multi-dose medications from
      pharmacies in Sweden was successively substituted with automated multi-dose drug
      dispensing (MDD). There are few studies evaluating the consequences of automated
      MDD with regard to patient safety, and those that investigate this issue are not
      very extensive. OBJECTIVES: To investigate Swedish health care professionals'
      perceived experience of automated MDD and its effects on patient adherence and
      patient safety. METHODS: Three questionnaire forms, one for physicians, nurses,
      and assistant nurses/nursing assistants, were developed based on reviews of the
      literature and pilot testing of the questions in the intended target groups. The
      target groups were health professionals prescribing or administrating MDD to
      patients. A sample (every sixth municipality) was drawn from the sampling frame
      of Swedish municipalities, resulting in 40 municipalities, about 14% of all
      municipalities in Sweden. Email addresses of general practitioners were obtained
      from county councils, while the municipalities assisted in getting contact
      details for nurses, assistant nurses and nursing assistants. A total of 915
      questionnaires were distributed electronically to physicians, 515 to nurses, and
      4,118 to assistant nurses/nursing assistants. The data were collected in
      September and October 2012. RESULTS: The response rate among physicians, nurses
      and assistant nurses/nursing assistants was 31%, 43% and 23%, respectively. The
      professionals reported that automated MDD reduces duplication of medication,
      contributes to correct dosages, helps patients take their medication at the right
      time, and reduces confusion among patients. Fifteen per cent of the physicians
      and about one-third of the nurses and assistant nurses/nursing assistants
      reported that generic substitution makes it more difficult for the patient to
      identify the various medicines available in the sachets. The physicians did,
      however, note that prescribing medicine to patients with automated MDD is
      complicated and can be a risk for patient safety. Both physicians and nurses
      requested more information on and training in automated MDD. They also asked for
      more medication reviews. CONCLUSIONS: The professionals generally had a positive
      attitude to automated MDD with regard to improved medication adherence, but said
      they believed that the electronic prescribing system posed a safety risk for
      patients.

PMID- 25580171
TI  - Patients' beliefs about generic medicines in Malaysia.
AB  - BACKGROUND: Acceptance of generic medicines by patients is an essential factor
      given that they are the end users of these medicines. In fact, adequate knowledge
      and positive perceptions are prerequisite to patients' acceptance and use of
      generic medicines. OBJECTIVE: To assess the current belief and views of patients
      about generic medicines in Malaysia. METHOD: This was a self-administered
      questionnaire-based study. The study was conducted with patients visiting
      outpatient pharmacy department at a tertiary care hospital in Malaysia. The
      Malaysian version of Generic Medicines Scale (GMS) was used. The GMS consists of
      two subscales: efficacy and similarity of generic medicines to original brand
      medicines. The efficacy subscale consists of 10 items while the similarity
      subscale consists of 6 items. The responses to the items were framed as a five
      point Likert scale (1=strongly disagree to 5=strongly agree). RESULTS: A total of
      202 out of 300 patients participated in the study, giving a response rate of
      67.3%. In this study, only 49% of them (n=99) knew the term 'generic medicine'.
      Moreover, only 53.5% of the respondents (n=108) believed that the efficacy of
      generic medicines was the same as original brand medicines. In terms of quality,
      only 44% of the respondents (n=89) disagreed that generic medicines were of a
      lower quality. About one third (n=65, 32.2%) believed that generic medicines were
      cheaper because they were less efficacious. In terms of side effects, 44.5% of
      the respondents (n=90) believed that generic medicines had the same side effect
      profile as original brand medicines. CONCLUSIONS: The study finding showed that
      almost half of the respondents had negative belief in generic medicines.
      Similarly, many patients were not aware of the similarities and differences
      between generic and original brand medicines. Therefore, there is a need to
      provide patients with adequate information about generic medicines.

PMID- 25580172
TI  - Defining 'elderly' in clinical practice guidelines for pharmacotherapy.
AB  - OBJECTIVE: To identify how 'elderly' patients are defined and considered within
      Australian clinical guidelines for the use of pharmacotherapy. METHOD: Guidelines
      pertaining to the use of pharmacotherapy, focusing on conditions described in
      National Health Priority Areas, were identified using databases (Medline, Google
      Scholar) and organisation websites (Department of Health and Ageing, National
      Heart Foundation, National Health and Medical Research Council). Guidelines were
      reviewed and qualitatively analysed to identify any references or definitions of
      'elderly' persons. RESULTS: Among the 20 guidelines reviewed, 3 defined 'elderly'
      by chronological age (i.e., years since birth) while the remaining 17 guidelines
      did not define 'elderly' in any way. All 20 guidelines used the term 'elderly',
      whilst some guidelines provided age (chronological)-based dosage recommendations
      suggesting an ageist or generalist approach in their representation of 'elderly',
      for which rationale was seldom provided. Thematic analysis of the statements
      revealed five key themes regarding how 'elderly' was considered within the
      guidelines, broadly describing 'elderly' persons as being frail and with altered
      pharmacology. Some guidelines also highlighted the limited evidence base to
      direct clinical decision-making. A continuum of perceptions of ageing also
      emerged out of the identified themes. CONCLUSION: Clinical practice guidelines
      currently do not adequately define 'elderly' persons and provide limited guidance
      on how to apply treatment recommendations to older persons. The representation of
      'elderly' in guidelines needs to be less based on chronological age or generic
      definitions focusing more on establishing a direct link between an individual
      patient's characteristics and the pharmacology of their prescribed medication.
      Clinical guidelines that do not offer any practical descriptions of the features
      of ageing that are specifically related to the use of pharmacotherapy, or how to
      assess these in individual patients, render decision-making challenging.

PMID- 25580174
TI  - Impact of a community-based diabetes self-management program on key metabolic
      parameters.
AB  - OBJECTIVE: Characterize the impact of a pharmacist-led diabetes self-management
      program on three key metabolic parameters: glycosylated hemoglobin (HbA1c), low
      density lipoprotein cholesterol (LDL-C), and mean arterial blood pressure (MAP)
      among employee health program participants. METHODS: A self-insured company in
      the Kansas City metropolitan area began offering a pharmacist-led diabetes self
      management program to eligible company employees and their dependents in 2008. A
      retrospective pre-post analysis was conducted to determine if the program
      affected key metabolic parameters in participants by determining mean change
      after one year of participation. RESULTS: Among 183 program participants, 65
      participants met inclusion criteria. All three key metabolic parameters were
      significantly reduced from baseline to one year of program participation: HbA1c
      decreased from 8.1 % to 7.3% (p=0.007); LDL-C decreased from 108.3 mg/dL to 96.4
      mg/dL (p=0.009); and MAP decreased from 96.1 to 92.3 mm Hg (p=0.005).
      CONCLUSIONS: The pharmacist-led diabetes self-management program demonstrated
      significant reductions in HbA1c, LDL-C, and MAP from baseline to one year of
      program participation. Improvements were statistically significant and clinically
      relevant for each parameter. Previous studies indicate these reductions may cause
      reduced overall healthcare costs.

PMID- 25580173
TI  - Economic evaluation of enhanced asthma management: a systematic review.
AB  - OBJECTIVES: To evaluate and compare full economic evaluation studies on the cost
      effectiveness of enhanced asthma management (either as an adjunct to usual care
      or alone) vs. usual care alone. METHODS: Online databases were searched for
      published journal articles in English language from year 1990 to 2012, using the
      search terms '"asthma" AND ("intervene" OR "manage") AND ("pharmacoeconomics" OR
      "economic evaluation" OR "cost effectiveness" OR "cost benefit" OR "cost
      utility")'. Hand search was done for local publishing. Only studies with full
      economic evaluation on enhanced management were included (cost consequences (CC),
      cost effectiveness (CE), cost benefit (CB), or cost utility (CU) analysis). Data
      were extracted and assessed for the quality of its economic evaluation design and
      evidence sources. RESULTS: A total of 49 studies were included. There were 3
      types of intervention for enhanced asthma management: education, environmental
      control, and self-management. The most cost-effective enhanced management was a
      mixture of education and self-management by an integrated team of healthcare and
      allied healthcare professionals. In general, the studies had a fair quality of
      economic evaluation with a mean QHES score of 73.7 (SD=9.7), and had good quality
      of evidence sources. CONCLUSION: Despite the overall fair quality of economic
      evaluations but good quality of evidence sources for all data components, this
      review showed that the delivered enhanced asthma managements, whether as single
      or mixed modes, were overall effective and cost-reducing. Whilst the availability
      and accessibility are an equally important factor to consider, the sustainability
      of the cost-effective management has to be further investigated using a longer
      time horizon especially for chronic diseases such as asthma.

PMID- 25580175
TI  - Trends in pharmacy staff's perception of patient safety in Swedish community
      pharmacies after re-regulation of conditions.
AB  - BACKGROUND: All changes in the regulation of pharmacies have an impact on the
      work carried out in pharmacies and also on patient safety, regardless of whether
      this is the intention or not. OBJECTIVE: To compare staff apprehension regarding
      some aspects of patient safety and quality in community pharmacies prior to and
      after the 2009 changes in regulation of the Swedish community pharmacy market.
      METHODS: Questionnaires targeted at pharmacy staff before and after the changes
      in regulation (in 2008, 2011/12, and 2012/13 respectively) used four identical
      items, making comparisons of some aspects possible. RESULTS: All four items
      demonstrated a significant decrease in the first survey after the changes as
      compared to before. In the second survey significant differences were found on
      the two items representing safety climate whereas the items representing team
      climate and management showed no significant differences. CONCLUSIONS: The
      comparison carried out in this study indicates a negative effect in Swedish
      community pharmacies on safety and quality issues, as experienced by pharmacy
      staff. It is recommended that the possible effects of healthcare reforms are
      assessed before implementation, in order to counteract conceivable decline in
      factors including patient safety and working conditions.

PMID- 25580176
TI  - Review of metformin and glyburide in the management of gestational diabetes.
AB  - BACKGROUND: Worldwide, gestational diabetes affects 15% of pregnancies. It is
      recommended in patients with gestational diabetes to initiate diet therapy and if
      this is not adequate, insulin is the next treatment modality. While insulin is
      the preferred drug therapy to manage gestational diabetes in the majority of
      women, it may not always be the best option for all women. OBJECTIVE: The purpose
      of this review is to assess the efficacy and safety of oral agents for treatment
      of gestational diabetes. METHODS: A literature search of the MEDLINE, Ovid
      databases and Google Scholar was performed using the search term "gestational
      diabetes" combined with each "metformin" and "glyburide". The time frame for the
      search was inception through August 2014. Randomized controlled trials and cohort
      (both prospective and retrospective) trials, published in English, with human
      participants were included. Studies included only pregnant women diagnosed with
      gestational diabetes. RESULTS: There were no significant differences in preterm
      deliveries, delivery modes, macrosomia, and birth weights and large for
      gestational age when utilizing glyburide vs insulin for gestational diabetes
      management. There were significantly higher neonatal intensive care unit
      admissions as well as longer lengths of stay for hypoglycemia and respiratory
      distress in babies whose mothers were treated with glyburide versus insulin. For
      the studies comparing metformin to insulin, there are no significant differences
      reported for birth weight, gestational age, delivery mode, prematurity and
      perinatal deaths. Women taking metformin may require supplemental insulin more
      frequently than those taking glyburide. CONCLUSION: Glyburide and metformin
      appear to be safe and effective to manage blood glucose in patients with
      gestational diabetes who prefer to not utilize insulin or who cannot afford
      insulin therapy. All other oral therapies to manage blood glucose levels during
      gestational diabetes should be reserved until additional evidence is available
      regarding safety and efficacy to both mother and fetus.

PMID- 25580177
TI  - A MATHEMATICAL INVESTIGATION OF THE ROLE OF INTRACRANIAL PRESSURE PULSATIONS AND
      SMALL GRADIENTS IN THE PATHOGENESIS OF HYDROCEPHALUS.
AB  - Cerebrospinal fluid (CSF) pulsations have been proposed as a possible causative
      mechanism for the ventricular enlargement that characterizes the neurological
      condition known as hydrocephalus. This paper summarizes recent work by the
      authors to anaylze the effect of CSF pulsations on brain tissue to determine if
      they are mechanically capable of enlarging the cerebral ventricles. First a
      poroelastic model is presented to analyze the interactions that occur between the
      fluid and porous solid constituents of brain tissue due to CSF pulsations. A
      viscoelastic model is then presented to analyze the effects of the fluid
      pulsations on the solid brain tissue. The combined results indicate that CSF
      pulsations in a healthy brain are incapable of causing tissue damage and thus the
      ventricular enlargement observed in hydrocephalus. Therefore they cannot be the
      primary cause of this condition. Finally, a hyper-viscoelastic model is presented
      and used to demonstrate that small long-term transmantle pressure gradients may
      be a possible cause of communicating hydrocephalus in infants.

PMID- 25580178
TI  - Force-Sensing Microneedle for Assisted Retinal Vein Cannulation*
AB  - Retinal vein cannulation (RVC) is a challenging procedure proposed for drug
      delivery into the very small retinal veins. The available glass cannulas for this
      procedure are both hard to visualize and fragile thereby limiting the feasibility
      of both robot-assisted and manual RVC approaches. In this study, we develop and
      test a new force-sensing RVC instrument that can be easily integrated with the
      existing manual and robotic devices. The tool enables (1) the measurement of the
      forces required for puncturing retinal veins in vivo and (2) an assistive method
      to inform the operator of the needle piercing the vessel wall. The fiber Bragg
      grating based sensor can be inserted into the eye through a small (? 0.9 mm)
      opening and provides a quantitative assessment at the tool tip with a resolution
      smaller than 0.25 mN. Assessment of forces during vessel penetration in the
      chorioallantoic membranes of chicken embryos have revealed a consistent sharp
      drop in tool tip force upon vessel puncture that has been used as a signature to
      provide auditory feedback to the user to stop needle advancement and begin drug
      delivery.

PMID- 25580179
TI  - Examining the link between traumatic events and delinquency among juvenile
      delinquent girls: A longitudinal study.
AB  - Researchers have postulated associations between childhood trauma and
      delinquency, but few have examined the direction of these relationships
      prospectively and, specifically, with samples of delinquent girls. The purpose of
      this study was to examine the relationship between traumatic events and
      delinquency for girls in the juvenile justice system using a cross-lagged model.
      Developmental differences in associations as a function of high school entry
      status were also examined. The sample included 166 girls in the juvenile justice
      system who were mandated to community-based out-of-home care due to chronic
      delinquency. Overall, study results provide evidence that trauma and delinquency
      risk pathways vary according to high school entry status. Implications for future
      research and practice are discussed.

PMID- 25580181
TI  - Comparison between diffuse infrared and acoustic transmission over the human
      skull.
AB  - Skull-induced distortion and attenuation present a challenge to both transcranial
      imaging and therapy. Whereas therapeutic procedures have been successful in
      offsetting aberration using from prior CTs, this approach impractical for
      imaging. In effort to provide a simplified means for aberration correction, we
      have been investigating the use of diffuse infrared light as an indicator of
      acoustic properties. Infrared wavelengths were specifically selected for tissue
      penetration; however this preliminary study was performed through bone alone via
      a transmission mode to facilitate comparison with acoustic measurements. The
      inner surface of a half human skull, cut along the sagittal midline, was
      illuminated using an infrared heat lamp and images of the outer surface were
      acquired with an IR-sensitive camera. A range of source angles were acquired and
      averaged to eliminate source bias. Acoustic measurement were likewise obtained
      over the surface with a source (1MHz, 12.7mm-diam) oriented parallel to the skull
      surface and hydrophone receiver (1mm PVDF). Preliminary results reveal a positive
      correlation between sound speed and optical intensity, whereas poor correlation
      is observed between acoustic amplitude and optical intensity.

PMID- 25580180
TI  - Registration of Zak ERA8 Soft White Spring Wheat Germplasm with Enhanced Response
      to ABA and Increased Seed Dormancy.
AB  - Zak ERA8 (ENHANCED RESPONSE to ABA8) (Reg. No. GP-966, PI 669443) is a unique
      line derived from soft white spring wheat (Triticum aestivum L.) cultivar Zak
      that has increased seed dormancy but after-ripens within 10 to 16 wk. The goal in
      developing this germplasm was to use increased seed dormancy to improve tolerance
      to preharvest sprouting, a problem that can cause severe economic losses. This
      germplasm was developed by USDA-ARS, Pullman, WA, in collaboration with
      Washington State University. Zak ERA8was tested under experimental number
      60.1.27.10. The ERA8mutation was generated by chemical mutagenesis followed by
      selection for the inability to germinate on abscisic acid (ABA) concentrations
      too low to inhibit wild-type Zak seed germination. The semidominant Zak ERA8 line
      has been backcrossed twice to wild-type Zak. Following the first backcross, Zak
      ERA8 showed similar morphological and grain quality traits to the original Zak
      cultivar.

PMID- 25580182
TI  - Changes in Religiosity After First Intercourse in the Transition to Adulthood.
AB  - Religiosity delays initiation of sexual behavior, but the association may be
      bidirectional, and individuals may become less religious after first intercourse.
      This study uses longitudinal data from college students to examine whether two
      aspects of religiosity change before and after first intercourse using multiphase
      growth curve models. Students' religiosity did not change in the six months
      preceding first intercourse, but on average they attended services less often and
      felt religion was less important in the twelve months after first intercourse.
      These findings suggest that sexual behavior can influence religious development
      in emerging adulthood, and underscore the importance of studying the impact of
      sexuality beyond the health outcomes typically studied, and of examining how life
      events influence religious development in adolescence and emerging adulthood.

PMID- 25580183
TI  - Free radicals in adolescent varicocele testis.
AB  - We examine the relationship between the structure and function of the testis and
      the oxidative and nitrosative stress, determined by an excessive production of
      free radicals and/or decreased availability of antioxidant defenses, which occur
      in the testis of adolescents affected by varicocele. Moreover, the effects of
      surgical treatment on oxidative stress were provided. We conducted a PubMed and
      Medline search between 1980 and 2014 using "adolescent," "varicocele," "free
      radicals," "oxidative and nitrosative stress," "testis," and "seminiferous
      tubules" as keywords. Cross-references were checked in each of the studies, and
      relevant articles were retrieved. We conclude that increased concentration of
      free radicals, generated by conditions of hypoxia, hyperthermia, and hormonal
      dysfunction observed in adolescent affected by varicocele, can harm germ cells
      directly or indirectly by influencing nonspermatogenic cells and basal lamina.
      With regard to few available data in current literature, further clinical trials
      on the pre- and postoperative ROS and RNS levels together with morphological
      studies of the cellular component of the testis are fundamental for complete
      comprehension of the role played by free radicals in the pathogenesis of
      adolescent varicocele and could justify its pharmacological treatment with
      antioxidants. 

PMID- 25580184
TI  - ELUCIDATING BRAIN CONNECTIVITY NETWORKS IN MAJOR DEPRESSIVE DISORDER USING
      CLASSIFICATION-BASED SCORING.
AB  - Graph theory is increasingly used in the field of neuroscience to understand the
      large-scale network structure of the human brain. There is also considerable
      interest in applying machine learning techniques in clinical settings, for
      example, to make diagnoses or predict treatment outcomes. Here we used support
      vector machines (SVMs), in conjunction with whole-brain tractography, to identify
      graph metrics that best differentiate individuals with Major Depressive Disorder
      (MDD) from nondepressed controls. To do this, we applied a novel feature-scoring
      procedure that incorporates iterative classifier performance to assess feature
      robustness. We found that small-worldness, a measure of the balance between
      global integration and local specialization, most reliably differentiated MDD
      from nondepressed individuals. Post-hoc regional analyses suggested that
      heightened connectivity of the subcallosal cingulate gyrus (SCG) in MDDs
      contributes to these differences. The current study provides a novel way to
      assess the robustness of classification features and reveals anomalies in large
      scale neural networks in MDD.

PMID- 25580185
TI  - Associations of Women's Substance Dependency Symptoms with Intimate Partner
      Violence.
AB  - Associations of substance dependencies and experiences with intimate partner
      violence (IPV) were examined in a community sample of 146 female participants in
      a longitudinal study of couples. The women with a history of dependence on hard
      drugs (but not alcohol, cannabis, or sedatives) were more likely to also have
      perpetrated IPV. However, only women dependent on cocaine were more likely to
      have been a victimized by their male partners. Psychological IPV was found to be
      more stable across time than physical IPV, but associations of substance abuse
      with IPV did not vary by IPV type. Findings were compared with results from a
      prior study of men's substance abuse and IPV that also found associations between
      dependence on hard drugs (but not alcohol dependence alone) and perpetration of
      IPV.

PMID- 25580187
TI  - Therapist Ethnicity and Treatment Orientation Differences in Multicultural
      Counseling Competencies.
AB  - This study examined the relationship between therapist characteristics,
      therapeutic orientations, person-level and agency-level practices with cultural
      competency among 221 Los Angeles County community mental health clinicians.
      Results from an online survey indicated that compared to White therapists, ethnic
      minority therapists were more personally involved in communities of color, more
      likely to use a cultural framework in clinical practice, and perceived their
      agencies to be more culturally sensitive. Ethnic minority therapists also
      reported greater multicultural (MC) awareness and better MC counseling
      relationships with their clients than White therapists. Personal involvement in
      communities of color accounted for ethnic differences in MC awareness and MC
      counseling relationships. Compared to therapists with a strictly non-behavioral
      (psychodynamic or humanistic) orientation, therapists with an eclectic (or
      integrative) therapy orientation reported having a higher level of community
      knowledge. Therapists with an eclectic orientation reported greater MC awareness
      than therapists with a non-behavioral orientation, while both eclectic and
      behavioral (cognitive behavioral or behavior modification) therapists recounted
      better MC counseling relationships with their clients than therapists with a non
      behavioral orientation. Community knowledge mediated eclectic vs. non-behavioral
      therapeutic orientation differences in MC awareness. Agency resources/linkages
      and outreach both moderated the relationship between therapeutic orientation and
      MC skills. Results suggest that if therapists become more personally involved
      with diverse populations, they will feel more culturally aware and feel like they
      have a better relationship with ethnic minority clients.

PMID- 25580186
TI  - Clinical Monitoring of Chronic Hepatitis C Based on its Natural History and
      Therapy.
AB  - Hepatitis C virus (HCV) infection is a major public health problem and a leading
      cause of chronic liver disease. Chronic HCV infection often follows a progressive
      course over years and can result in cirrhosis, hepatocellular carcinoma, and need
      for liver transplantation. In the United States alone, the estimated prevalence
      of HCV infection is up to 5.1 million persons. The optimal approach to detecting
      HCV infection is to screen persons for possible history of risks of exposure to
      virus and to test those selected individuals with risk factors. Both host and
      viral factors may be important contributors to the natural history of HCV.
      Currently, effective pharmacologic therapy are available to induce sustained
      virologic response (SVR) or virologic "cure," which results in improved morbidity
      and mortality. Patient education before treatment is essential and should include
      a full discussion of potential side effects. It is important to work
      collaboratively and closely with patients to ensure early recognition of adverse
      events and to effectively manage them in order to ensure treatment compliance.
      This paper provides a thorough overview on screening for the diagnosis, clinical
      management, and treatment indications and contraindications for chronic hepatitis
      C.

PMID- 25580188
TI  - Differential Impact of the Monovalent Ions Li+, Na+, K+, and Rb+ on DNA
      Conformational Properties.
AB  - The present report demonstrates that the conformational properties of DNA in
      solution are sensitive to the type of monovalent ion. Results are based on the
      ability of a polarizable force field using the classical Drude oscillator to
      reproduce experimental solution X-ray scattering data more accurately than two
      nonpolarizable DNA models, AMBER Parmbsc0 and CHARMM36. The polarizable model is
      then used to calculate scattering profiles of DNA in the presence of four
      different monovalent salts, LiCl, NaCl, KCl, and RbCl, showing the conformational
      properties of DNA to vary as a function of ion type, with that effect being
      sequence-dependent. The primary conformational mode associated with the
      variations is contraction of the DNA minor groove width with decreasing cation
      size. These results indicate that the Drude polarizable model provides a more
      realistic representation of ion-DNA interactions than additive models that may
      lead to a new level of understanding of the physical mechanisms driving salt
      mediated biological processes involving nucleic acids.

PMID- 25580189
TI  - Non-compact cardiomyopathy or ventricular non-compact syndrome?
AB  - Ventricular myocardial non-compaction has been recognized and defined as a
      genetic cardiomyopathy by American Heart Association since 2006. The argument on
      the nomenclature and pathogenesis of this kind of ventricular myocardial non
      compaction characterized by regional ventricular wall thickening and deep
      trabecular recesses often complicated with chronic heart failure, arrhythmia and
      thromboembolism and usually overlap the genetics and phenotypes of other kind of
      genetic or mixed cardiomyopathy still exist. The proper classification and
      correct nomenclature of the non-compact ventricles will contribute to the
      precisely and completely understanding of etiology and its related patho
      physiological mechanism for a better risk stratification and more personalized
      therapy of the disease individually. All of the genetic heterogeneity and
      phenotypical overlap and the variety in histopathological, electromechanical and
      clinical presentation indicates that some of the cardiomyopathies might just be
      the different consequence of myocardial development variations related to gene
      mutation and phenotype of one or group genes induced by the interacted and
      disturbed process of gene modulation at different links of gene function
      expression and some other etiologies. This review aims to establish a new concept
      of "ventricular non-compaction syndrome" based on the demonstration of the
      current findings of etiology, epidemiology, histopathology and echocardiography
      related to the disorder of ventricular myocardial compaction and myocardial
      electromechanical function development. 

PMID- 25580191
TI  - Geometric and functional change of both ventricles after atrial ventricular
      septal defect closure.

PMID- 25580190
TI  - Role of echocardiography in the management of cardiac disease in women.
AB  - The widespread use of echocardiography has contributed to the early recognition
      of several distinct cardiac diseases in women. During pregnancy, safe monitoring
      of the disease process, as well as a better understanding of hemodynamics, is
      possible. During the use of potentially cardiotoxic drugs for breast cancer
      chemotherapy, echocardiographic patient monitoring is vital. Compared to men, the
      addition of an imaging modality to routine electrocardiogram monitoring during
      stress testing is more informative for diagnosing coronary disease in women. This
      review briefly discusses the role of echocardiography in the management of
      several women-specific cardiac diseases where echocardiography plays a pivotal
      role in disease management. 

PMID- 25580192
TI  - Segmental Analysis of Right Ventricular Longitudinal Deformation in Children
      before and after Percutaneous Closure of Atrial Septal Defect.
AB  - BACKGROUND: The aim of study is to identify the dependence of right ventricular
      (RV) free wall longitudinal deformation on ventricular loading through segmental
      approach in relatively large number of patients with atrial septal defect (ASD).
      METHODS: Patients with ASD (n = 114) and age matched healthy children (n = 60)
      were echocardiographically examined the day before percutaneous device closure
      and within 24 hours afterwards. RV free wall deformation parameters, strain (e)
      and strain rate (SR), were analyzed in the apical (eA, SRA) and basal (eB, SRB)
      segments. Measured deformation parameters were adjusted for RV size (eAL, SRAL,
      eBL, SRBL) by multiplying by body surface area indexed RV longitudinal dimension.
      Regression analyses determined the relationships of these deformation parameters
      with RV loading parameters that were measured by catheterization. RESULTS: eBL
      and SRBL were not different between pre-closure patients and controls (p = 0.245,
      p = 0.866), and were decreased post-closure (p = 0.001, p = 0.018). Post-closure
      eBL was lower than in controls (p = 0.001). Pre-closure eAL and SRAL were higher
      than in controls (p = 0.001, p < 0.001), but decreased after closure (all p <
      0.001). The pulmonary to systemic flow ratio was related to procedural
      differences of eBL (p = 0.017) and of SRBL (p = 0.019). RV end diastolic pressure
      was negatively related to post-closure eBL (p = 0.020) and post-closure SRBL (p =
      0.012), and the procedural SRBL difference (p = 0.027). CONCLUSION: The
      longitudinal deformation of the RV basal segment is dependent and its remodeling
      is also dependent on volume loading in children with ASD.

PMID- 25580193
TI  - Myocardial mechanics in a rat model with banding and debanding of the ascending
      aorta.
AB  - BACKGROUND: Aortic banding and debanding models have provided useful information
      on the development and regression of left ventricular hypertrophy (LVH). In this
      animal study, we aimed to evaluate left ventricular (LV) deformation related to
      the development and regression of LVH. METHODS: Minimally invasive ascending
      aorta banding was performed in rats (10 Sprague Dawley rats, 7 weeks). Ten rats
      underwent a sham operation. Thirty-five days later, the band was removed.
      Echocardiographic and histopathologic analysis was assessed at pre-banding, 35
      days of banding and 14 days of debanding. RESULTS: Banding of the ascending aorta
      created an expected increase in the aortic velocity and gradient, which
      normalized with the debanding procedure. Pressure overload resulted in a robust
      hypertrophic response as assessed by gross and microscopic histology,
      transthoracic echocardiography [heart weight/tibia length (g/m); 21.0 +/- 0.8 vs.
      33.2 +/- 2.0 vs. 26.6 +/- 2.8, p < 0.001]. The circumferential (CS) and radial
      strains were not different between the groups. However, there were significant
      differences in the degree of fibrosis according to the banding status (fibrosis;
      0.10 +/- 0.20% vs. 5.26 +/- 3.12% vs. 4.03 +/- 3.93%, p = 0.003), and global CS
      showed a significant correlation with the degree of myocardial fibrosis in this
      animal model (r = 0.688, p = 0.028). CONCLUSION: In this animal study, simulating
      a severe LV pressure overload state, a significant increase in the LV mass index
      did not result in a significant reduction in the LV mechanical parameters. The
      degree of LV fibrosis, which developed with pressure overload, was significantly
      related to the magnitude of left ventricular mechanics.

PMID- 25580194
TI  - Endurance and Strength Athlete's Heart: Analysis of Myocardial Deformation by
      Speckle Tracking Echocardiography.
AB  - BACKGROUND: Intensive training induces two morphological myocardial typologies of
      athlete's heart. Endurance training (ET) induces eccentric remodeling,
      bradycardia and better diastolic filling. Strength training (ST) determines
      concentric chamber remodelling maintaining a normal heart rate (HR). Aim of the
      study was to compare ET and ST athletes' heart using speckle tracking
      echocardiography (STE). METHODS: 33 professional ET, 36 ST athletes, and 17
      healthy controls (CT) were enrolled. All subjects underwent standard
      transthoracic echocardiography at rest and STE. RESULTS: In ET group, HR was
      lower than ST group and CT group (p < 0.001; p < 0.01). ET group had higher E/A
      ratio than ST group and CT group (p < 0.01; p < 0.001). The left ventricular
      apical circumferential strain in ET group was lower than ST group and CT group (
      21.6 +/- 4.1% vs. -26.8 +/- 7.7%, p < 0.05; vs. -27.8 +/- 5.6%, p < 0.01). ET
      group had lower left ventricular twist (LVT) and untwisting (UTW) than ST group
      (6.2 +/- 0.1 degrees  vs. 12.0 +/- 0.1 degrees , p < 0.01; -67.3 +/- 22.9 degrees
      /s vs. -122.5 +/- 52.8 degrees /s, p < 0.01) and CT group (10.0 +/- 0.1 degrees ,
      p < 0.01; -103.3 +/- 29.3 degrees /s, p < 0.01). The univariate analysis showed
      significant correlation between E/A ratio and HR (r = -0.54; p < 0.001), LVT (r =
      -0.45; p < 0.01), UTW (r = 0.24; p < 0.05). At the multivariate analysis only HR
      was confirmed as independent predictor of diastolic function in all groups (Beta 
      0.52; p < 0.001). CONCLUSION: In ET there was a better global systolic and
      diastolic functional reserve at rest observed with strain analysis and it maybe
      depended on autonomic modulation.

PMID- 25580195
TI  - Left atrial intramural hematoma after removal of atrial myxoma: cardiac magnetic
      resonance in the differential diagnosis of intra-cardiac mass.
AB  - Left atrial (LA) dissection is a rare entity, which is, in most cases, observed
      after valvular intervention. Transesophageal echocardiography (TEE) is considered
      to be a modality of choice in the diagnosis of LA dissection. However, LA
      dissection might be missed clinically in the absence of significant hemodynamic
      changes, and moreover physicians are occasionally reluctant to perform TEE due to
      its semi-invasiveness. Recently, cardiac magnetic resonance (CMR) has been
      introduced as a modality to perform different roles to existing imaging
      modalities, such as echocardiography. Given that CMR can provide information on
      tissue characteristics, it may give incremental information to TEE. We here
      present a rare case of LA dissection following LA myxoma removal, where CMR can
      make a correct diagnosis and guide management strategy. 

PMID- 25580196
TI  - Pulmonary Artery Stenosis due to Lung Carcinoma: A Rare Cause of Dyspnea.
AB  - Acquired bilateral pulmonary artery stenosis in adults due to lung malignancy is
      infrequently reported. We describe an adult male who presented to us with chief
      complaints of dyspnea on exertion and one episode of hemoptysis. Two dimensional
      transthoracic echocardiography with color Doppler showed presence of an extra
      cardiac mass causing severe extrinsic compression of both the right and left
      pulmonary artery leading to high pressure severe tricuspid regurgitation and
      extension of the mass into the left atrium. Three dimensional transthoracic
      echocardiography clearly delineated the anatomy of the left atrial mass and its
      surrounding anatomical relationship. The diagnosis of non small cell lung
      carcinoma was confirmed by multidetector computed tomography (MDCT) and with MDCT
      guided biopsy with histopathology. Patient succumbed one month later due to an
      episode of massive hemoptysis. 

PMID- 25580197
TI  - Total anomalous pulmonary venous return in siblings.
AB  - Total anomalous pulmonary venous return (TAPVR) is a rare and critical congenital
      vascular anomaly that requires an early operation. However, initial symptoms of
      TAPVR may be non-specific, and cardiovascular findings may be minimal. The heart
      may not be enlarged and there is often no cardiac murmur. Without cardiac murmur,
      these symptoms are similar to those of respiratory distress syndrome in newborns.
      Therefore, a high degree of suspicion and an early diagnosis of TAPVR are
      important. This condition generally occurs without a family history and has a low
      recurrence rate, but several familial cases, including siblings, have been
      reported worldwide. Additionally, several chromosomal or gene abnormalities
      associated with TAPVR have been reported. In the case presented here, two
      brothers with a 6-year age gap were diagnosed with TAPVR. Surgery was performed
      without cardiac or neurological complications. This is the first report on TAPVR
      in siblings in Korea. 

PMID- 25580198
TI  - Atrial septal defect with normal pulmonary arterial pressure in adult cyanotic
      patient.
AB  - A 22-year-old male presented with recurrent stroke, central cyanosis, and
      dyspnea. Transesophageal echocardiography and cardiac catheterization revealed
      bidirectional shunt flow through atrial septal defect (ASD) without pulmonary
      arterial hypertension. The orifice of inferior vena cava facing towards ASD
      opening led partially right to left shunt resulting in cyanosis with normal
      pulmonary arterial pressure. 

PMID- 25580199
TI  - Cardiac involvement in hypereosinophilia associated with toxocariasis.
AB  - Cardiac involvement in hypereosinophilia is rare; when present, it manifests as
      ventricular thickening, usually with fibrous tissue and mural thrombosis. We
      present a case of a 57-year-old man with an abnormal right ventricular apex with
      eosinophilia, which was caused by Toxocara canis infection. 

PMID- 25580200
TI  - Severe form of tetralogy of fallot: late presentation.

PMID- 25580201
TI  - Valve in Valve: Three-Dimensional Transoesophageal Echocardiogram and Multi-Slice
      CT Images of Bio-Prosthetic Aortic Valve Replaced by Medtronic CoreValve.

PMID- 25580202
TI  - Examination of wrist and hip actigraphy using a novel sleep estimation procedure
      ?
AB  - OBJECTIVE: Improving and validating sleep scoring algorithms for actigraphs
      enhances their usefulness in clinical and research applications. The MTI(r)
      device (ActiGraph, Pensacola, FL) had not been previously validated for sleep.
      The aims were to (1) compare the accuracy of sleep metrics obtained via wrist-
      and hip-mounted MTI(r) actigraphs with polysomnographic (PSG) recordings in a
      sample that included both normal sleepers and individuals with presumed sleep
      disorders; and (2) develop a novel sleep scoring algorithm using spline
      regression to improve the correspondence between the actigraphs and PSG. METHODS:
      Original actigraphy data were amplified and their pattern was estimated using a
      penalized spline. The magnitude of amplification and the spline were estimated by
      minimizing the difference in sleep efficiency between wrist- (hip-) actigraphs
      and PSG recordings. Sleep measures using both the original and spline-modified
      actigraphy data were compared to PSG using the following: mean sleep summary
      measures; Spearman rank-order correlations of summary measures; percent of minute
      by-minute agreement; sensitivity and specificity; and Bland-Altman plots.
      RESULTS: The original wrist actigraphy data showed modest correspondence with
      PSG, and much less correspondence was found between hip actigraphy and PSG. The
      spline-modified wrist actigraphy produced better approximations of interclass
      correlations, sensitivity, and mean sleep summary measures relative to PSG than
      the original wrist actigraphy data. The spline-modified hip actigraphy provided
      improved correspondence, but sleep measures were still not representative of PSG.
      DISCUSSION: The results indicate that with some refinement, the spline regression
      method has the potential to improve sleep estimates obtained using wrist
      actigraphy.

PMID- 25580203
TI  - On-chip detection of a single nucleotide polymorphism without polymerase
      amplification.
AB  - A nanoparticle-assembled photonic crystal (PC) array was used to detect single
      nucleotide polymorphism (SNP). The assay platform with PC nanostructure enhanced
      the fluorescent signal from nanoparticle-hybridized DNA complexes due to phase
      matching of excitation and emission. Nanoparticles coupled with probe DNA were
      trapped into nanowells in an array by using an electrophoretic particle
      entrapment system. The PC/DNA assay platform was able to identify a 1 base pair
      (bp) difference in synthesized nucleotide sequences that mimicked the mutation
      seen in a feline model of human autosomal dominant polycystic kidney disease
      (PKD) with a sensitivity of 0.9 fg/mL (50 aM)-sensitivity, which corresponds to
      30 oligos/array. The reliability of the PC/DNA assay platform to detect SNP in a
      real sample was demonstrated by using genomic DNA (gDNA) extracted from the urine
      and blood of two PKD- wild type and three PKD positive cats. The standard curves
      for PKD positive (PKD+) and negative (PKD-) DNA were created using two feline
      urine samples. An additional three urine samples were analyzed in a similar
      fashion and showed satisfactory agreement with the standard curve, confirming the
      presence of the mutation in affected urine. The limit of detection (LOD) was
      0.005 ng/mL which corresponds to 6 fg per array for gDNA in urine and blood. The
      PC system demonstrated the ability to detect a number of genome equivalents for
      the PKD SNP that was very similar to the results reported with real time
      polymerase chain reaction (PCR). The favorable comparison with quantitative PCR
      suggests that the PC technology may find application well beyond the detection of
      the PKD SNP, into areas where a simple, cheap and portable nucleic acid analysis
      is desirable.

PMID- 25580204
TI  - 3,5-Diamino-1,2,4-triazoles as a novel scaffold for potent, reversible LSD1
      (KDM1A) inhibitors.
AB  - The chromatin remodeling amine oxidase lysine-specific demethylase 1 (LSD1) has
      become an attractive target for the design of specific inhibitors with
      therapeutic potential. We, and others, have described LSD1 inhibitors that have
      potential as antitumor agents. Many of the currently known LSD1 inhibitors are
      poor drug candidates, or are structurally based on the tranylcypromine backbone,
      thus increasing the potential for off-target effects mediated by other amine
      oxidases. We now describe a series of potent LSD1 inhibitors based on a novel
      1,2,4-triazole scaffold; these inhibitors show a high degree of specificity for
      LSD1 in vitro, and cause increases in cellular histone 3 dimethyllysine 4
      (H3K4me2), a gene transcription activating mark. Importantly, these inhibitors
      are not toxic to mammalian cells in vitro, and thus they may show utility in the
      treatment of epigenetically-based diseases where cell death is not a desired
      endpoint Figure 1. Structures of LSD1 inhibitors 1, verlindamycin 2,
      (bis)thioureas 3, amidoxime 4, cyclic peptide 5, N3-(2-chloro-6-phenoxybenzyl)-4H
      1,2,4-triazole-3,5-diamine 6 and N3,N5-bis(2-methoxybenzyl)-1H-1,2,4-triazole-3,5
      diamine 7.

PMID- 25580205
TI  - Utility of faecal calprotectin in inflammatory bowel disease (IBD): what cut-offs
      should we apply?
AB  - BACKGROUND: Faecal calprotectin (FC), a cytosolic protein released by neutrophils
      (S100 family) in response to inflammation, is a simple, non-invasive test that
      can be used to differentiate irritable bowel syndrome (IBS) with inflammatory
      bowel disease (IBD), where there can be considerable symptom overlap. AIMS AND
      METHODS: The aims of the study were (1) to be able to predict the ability of FC
      to exclude IBD and determine cut-offs when in remission, (2) to investigate the
      effects of time and temperature on stability of FC and (3) compare three ELISA
      kits to measure FC: Buhlmann, PhiCal v1 and PhiCal v2. A total of 311 patients
      with altered bowel habit were tested for FC; 144 with IBS, 148 with IBD and 19
      with other organic causes. RESULTS: Sensitivity and specificity of FC (with
      PhiCal v2 kit) to distinguish between functional disorder (IBS) and IBD using cut
      off 50 MUg/g were 88% and 78%, respectively, with a negative predictive value of
      87%. Area under the receiver operating curve was 0.84 (CI 0.78 to 0.90). For
      those with IBD, FC values below 250 MUg/g corresponded with remission of disease
      with a sensitivity and specificity of 90% and 76%, respectively. Area under the
      receiver operating curve was 0.93 (CI 0.89 to 0.97). FC was stable once extracted
      and frozen for up to 2.5 months. Pearson correlation was good between Buhlmann
      assay and PhiCal v2 (r2 = 0.95). CONCLUSIONS: FC has up to 87% negative
      predictive value to exclude IBD, and cut-offs less than 250 MUg/g had 90%
      sensitivity to determine remission in IBD. Once frozen, FC is stable and the
      ELISA monoclonal plates were broadly comparable.

PMID- 25580206
TI  - Non-alcoholic fatty liver disease is associated with higher levels of objectively
      measured sedentary behaviour and lower levels of physical activity than matched
      healthy controls.
AB  - BACKGROUND AND AIMS: Physical activity is a key determinant of metabolic control
      and is recommended for people with non-alcoholic fatty liver disease (NAFLD),
      usually alongside weight loss and dietary change. To date, no studies have
      reported the relationship between objectively measured sedentary behaviour and
      physical activity, liver fat and metabolic control in people with NAFLD, limiting
      the potential to target sedentary behaviour in clinical practice. This study
      determined the level of sedentary behaviour and physical activity in people with
      NAFLD, and investigated links between physical activity, liver fat and glucose
      control. METHODS: Sedentary behaviour, physical activity and energy expenditure
      were assessed in 37 adults with NAFLD using a validated multisensor array over 7
      days. Liver fat and glucose control were assessed, respectively, by 1H-MRS and
      fasting blood samples. Patterns of sedentary behaviour were assessed by power law
      analyses of the lengths of sedentary bouts fitted from raw sedentary data. An age
      and sex-matched healthy control group wore the activity monitor for the same time
      period. RESULTS: People with NAFLD spent approximately half an hour extra a day
      being sedentary (1318+/-68 vs1289+/-60 mins/day; p<0.05) and walked 18% fewer
      steps (8483+/-2926 vs 10377+/-3529 steps/day; p<0.01). As a consequence, active
      energy expenditure was reduced by 40% (432+/-258 vs 732+/-345 kcal/day; p<0.01)
      and total energy expenditure was lower in NAFLD (2690+/-440 vs 2901+/-511
      kcal/day; p<0.01). Power law analyses of the lengths of sedentary bouts
      demonstrated that patients with NAFLD also have a lower number of transitions
      from being sedentary to active compared with controls (13+/-0.03 vs15+/-0.03%;
      p<0.05). CONCLUSIONS: People with NAFLD spend more time sedentary and undertake
      less physical activity on a daily basis than healthy controls. High levels of
      sedentary behaviour and low levels of physical activity represent a therapeutic
      target that may prevent progression of metabolic conditions and weight gain in
      people with NAFLD and should be considered in clinical care.

PMID- 25580207
TI  - Guidance: The practical management of the gastrointestinal symptoms of pelvic
      radiation disease.
AB  - BACKGROUND: A recent randomised trial suggested that an algorithmic approach to
      investigating and managing gastrointestinal symptoms of pelvic radiation disease
      (PRD) is beneficial and that specially trained nurses can manage patients as
      effectively as a gastroenterologist. AIMS: The aim of the development and peer
      review of the guide was to make the algorithm used in the trial accessible to all
      levels of clinician. METHODS: Experts who manage patients with PRD were asked to
      review the guide, rating each section for agreement with the recommended measures
      and suggesting amendments if necessary. Specific comments were discussed and
      incorporated as appropriate, and this process was repeated for a second round of
      review. RESULTS: 34 gastroenterologists, 10 nurses, 9 dietitians, 7 surgeons and
      5 clinical oncologists participated in round one. Consensus (defined
      prospectively as 60% or more panellists selecting 'strongly agree' or 'agree')
      was reached for 27 of the original 28 sections in the guide, with a median of 75%
      of panellists agreeing with each section. 86% of panellists agreed that the guide
      was acceptable for publication or acceptable with minor revisions. 55 of the
      original 65 panellists participated in round two. 89% agreed it was acceptable
      for publication after the first revision. Further minor amendments were made in
      response to round two. CONCLUSIONS: Development of the guide in response to
      feedback included ? improvement of occasional algorithmic steps ? a more user
      friendly layout ? clearer timeframes for referral to other teams ? expansion of
      reference list ? addition of procedures to the appendix.

PMID- 25580208
TI  - An Improved Catalyst Architecture for Rhodium (III) Catalyzed C-H Activation and
      its Application to Pyridone Synthesis.
AB  - We have developed a method for preparing pyridones from the coupling reaction of
      acrylamides and alkynes with either stoichometric Cu(OAc)2 or catalytic Cu(OAc)2
      and air as oxidants. In the course of these studies, it was found that a larger
      ligand, 1,3-di-tert-butylcyclopentadienyl (termed Cpt) results in higher degrees
      of regioselectivity in the alkyne insertion event. The transformation tolerates a
      broad variety of alkynes and acrylamides. Furthermore, Cpt and Cp* demonstrate
      similar catalytic activity. This similarity allows for mechanistic studies to be
      undertaken which suggest a difference in mechanism between this reaction and the
      previously studied benzamide system.

PMID- 25580209
TI  - Targeting the endoplasmic reticulum with a membrane-interactive luminescent
      ruthenium(ii) polypyridyl complex?Electronic supplementary information (ESI)
      available: Experimental details, characterization of 2 and Fig. S1-S6. See DOI:
      10.1039/c3sc51725jClick here for additional data file.
AB  - The characterization and bioactivity of the dinuclear ruthenium(ii) complex
      [(Ru(DIP)2)2(tpphz)]4+ (DIP = 4,7-diphenyl-1,10-phenanthroline and tpphz =
      tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) is reported. This new
      complex is found to be luminescent in acetonitrile, where excitation into MLCT
      (metal-to-ligand charge-transfer) bands in the visible area of the spectrum
      (lambdaex = 450 nm, epsilon = 45 000 M-1 cm-1) result in red emission
      (lambdaem,max = 620 nm, PhiMLCT = 0.017). Aqueous in vitro binding studies
      indicate that this complex binds to duplex DNA with an affinity of 1.8 * 106 M-1
      through a non-classical groove-binding interaction, however, unlike the parent
      complex [(Ru(phen)2)2(tpphz)]4+ (phen = 1,10-phenanthroline), it also displays an
      increase in MLCT luminescence on addition of liposomes. Confocal microscopy and
      TEM studies show that this lipophilic complex targets the endoplasmic reticulum
      of eukaryotic cells, where it functions as an imaging agent for this organelle,
      and cytotoxicity studies in human cancer cell lines indicate a comparable potency
      to the anti-cancer drug cisplatin.

PMID- 25580210
TI  - Oxidative dearomatisation: the key step of sorbicillinoid biosynthesis?Electronic
      supplementary information (ESI) available: Containing all experimental details.
      See DOI: 10.1039/c3sc52911hClick here for additional data file.
AB  - An FAD-dependent monooxygenase encoding gene (SorbC) was cloned from Penicillium
      chrysogenum E01-10/3 and expressed as a soluble protein in Escherichia coli. The
      enzyme efficiently performed the oxidative dearomatisation of sorbicillin and
      dihydrosorbicillin to give sorbicillinol and dihydrosorbicillinol respectively.
      Bioinformatic examination of the gene cluster surrounding SorbC indicated the
      presence of two polyketide synthase (PKS) encoding genes designated sorbA and
      sorbB. The gene sorbA-encodes a highly reducing iterative PKS while SorbB encodes
      a non-reducing iterative PKS which features a reductive release domain usually
      involved in the production of polyketide aldehydes. Using these observations and
      previously reported results from isotopic feeding experiments a new and simpler
      biosynthetic route to the sorbicillin class of secondary metabolites is proposed
      which is consistent with all reported experimental results.

PMID- 25580211
TI  - Strain-promoted sydnone bicyclo-[6.1.0]-nonyne cycloaddition?Electronic
      supplementary information (ESI) available: Full experimental details, 1H/13C NMR
      spectral data, protein synthesis and purification. See DOI: 10.1039/c3sc53332h.
AB  - The discovery and exploration of bioorthogonal chemical reactions and the
      biosynthetic incorporation of their components into biomolecules for specific
      labelling is an important challenge. Here we describe the reaction of a phenyl
      sydnone 1,3-dipole with a bicyclononyne dipolarophile. This strain-promoted
      reaction proceeds without transition metal catalysis in aqueous buffer, at
      physiological temperature, and pressure with a rate comparable to that of other
      bioorthogonal reactions. We demonstrate the quantitative and specific labelling
      of a genetically encoded bicyclononyne with a sydnone fluorophore conjugate,
      demonstrating the utility of this approach for bioorthogonal protein labelling.

PMID- 25580212
TI  - Preparation and Properties of an MnIV-Hydroxide Complex: Proton and Electron
      Transfer at a Mononuclear Manganese Site and its Relationship to the Oxygen
      Evolving Complex within Photosystem II.
AB  - Photosynthetic water oxidation is catalyzed by a Mn4O5Ca cluster with an
      unprecedented arrangement of metal ions in which a single manganese center is
      bonded to a distorted Mn3O4Ca cubane-like structure. Several mechanistic
      proposals describe the unique manganese center as a site for water binding and
      subsequent formation of a high valent Mn-oxo center that reacts with a M-OH unit
      (M = Mn or CaII) to form the O-O bond. The conversion of low valent Mn-OHn (n =
      1,2) to a Mn-oxo species requires that a single manganese site be able to
      accommodate several oxidation states as the water ligand is deprotonated. To
      study these processes, the preparation and characterization of a new monomeric
      MnIV-OH complex is described. The MnIV-OH complex completes a series of well
      characterized Mn-OH and Mn-oxo complexes containing the same primary and
      secondary coordination spheres; this work thus demonstrates that a single ligand
      can support mononuclear Mn complexes spanning four different oxidation states (II
      through V) with oxo and hydroxo ligands that are derived from water. Moreover, we
      have completed a thermodynamic analysis based on this series of manganese
      complexes to predict the formation of high valent Mn-oxo species; we demonstrated
      that the conversion of a MnIV-OH species to a MnV-oxo complex would likely occur
      via a stepwise proton transfer-electron transfer mechanism. The large
      dissociation energy for the MnIVO-H bond (~95 kcal/mol) diminished the likelihood
      that other pathways are operative within a biological context. Furthermore, these
      studies showed that reactions between Mn-OH and Mn-oxo complexes lead to non
      productive, one-electron processes suggesting that initial O-O bond formation
      with the OEC does not involve an Mn-OH unit.

PMID- 25580214
TI  - Target discovery of acivicin in cancer cells elucidates its mechanism of growth
      inhibition?Electronic supplementary information (ESI) available: Synthesis,
      cloning, protein expression, purification and biochemical assays. See DOI:
      10.1039/c4sc02339k.
AB  - Acivicin is a natural product with diverse biological activities. Several decades
      ago its clinical application in cancer treatment was explored but failed due to
      unacceptable toxicity. The causes behind the desired and undesired biological
      effects have never been elucidated and only limited information about acivicin
      specific targets is available. In order to elucidate the target spectrum of
      acivicin in more detail we prepared functionalized derivatives and applied them
      for activity based proteomic profiling (ABPP) in intact cancer cells. Target
      deconvolution by quantitative mass spectrometry (MS) revealed a preference for
      specific aldehyde dehydrogenases. Further in depth target validation confirmed
      that acivicin inhibits ALDH4A1 activity by binding to the catalytic site. In
      accordance with this, downregulation of ALDH4A1 by siRNA resulted in a severe
      inhibition of cell growth and might thus provide an explanation for the cytotoxic
      effects of acivicin.

PMID- 25580215
TI  - Mechanistic insights into hydroacylation with non-chelating aldehydes?Electronic
      supplementary information (ESI) available: Materials and methods, reaction
      procedures, characterization data. CCDC 1012849. For ESI and crystallographic
      data in CIF or other electronic format see DOI: 10.1039/c4sc02026jClick here for
      additional data file.
AB  - The combination of a small-bite-angle diphosphine
      bis(dicyclohexylphosphino)methane (dcpm) and [Rh(cod)OMe]2 catalyses the
      hydroacylation of 2-vinylphenols with a wide range of non-chelating aldehydes.
      Here we present a detailed experimental study that elucidates the factors
      contributing to the broad aldehyde scope and high reactivity. A variety of
      catalytically relevant intermediates were isolated and a
      [Rh(dcpm)(vinylphenolate)] complex was identified as the major catalytically
      relevant species. A variety of off-cycle intermediates were also identified that
      can re-enter the catalytic cycle by substrate- or 1,5-cyclooctadiene-mediated
      pathways. Saturation kinetics with respect to the 2-vinylphenol were observed,
      and this may contribute to the high selectivity for hydroacylation over aldehyde
      decarbonylation. A series of deuterium labelling experiments and Hammett studies
      support the oxidative addition of Rh to the aldehyde C-H bond as an irreversible
      and turnover-limiting step. The small bite angle of dcpm is crucial for lowering
      the barrier of this step and providing excellent reactivity with a variety of
      aldehydes.

PMID- 25580216
TI  - Architecture of the superintegron in Vibrio cholerae: identification of core and
      unique genes.
AB  - BACKGROUND: Vibrio cholerae, the etiologic agent of cholera, is indigenous to
      aquatic environments. The V. cholerae genome consists of two chromosomes; the
      smallest of these harbors a large gene capture and excision system called the
      superintegron (SI), of ~120 kbp. The flexible nature of the SI that results from
      gene cassette capture, deletion and rearrangement is thought to make it a hotspot
      of V. cholerae diversity, but beyond the basic structure it is not clear if there
      is a core genome in the SI and if so how it is structured. The aim of this study
      was to explore the core genome structure and the differences in gene content
      among strains of V. cholerae. METHODS: From the complete genomes of seven V.
      cholerae and one Vibrio mimicus representative strains, we recovered the SI
      sequences based on the locations of the structural gene IntI4 and the V. cholerae
      repeats. Analysis of the pangenome, including cluster analysis of functional
      genes, pangenome profile analysis, genetic variation analysis of functional
      genes, strain evolution analysis and function enrichment analysis of gene
      clusters, was performed using a pangenome analysis pipeline in addition to the R
      scripts, splitsTree4 and genoPlotR. RESULTS AND CONCLUSIONS: Here, we reveal the
      genetic architecture of the V. cholerae SI. It contains eight core genes when V.
      mimicus is included and 21 core genes when only V. cholerae strains are
      considered; many of them are present in several copies. The V. cholerae SI has an
      open pangenome, which means that V. cholerae may be able to import new gene
      cassettes to SI. The set of dispensable SI genes is influenced by the niche and
      type species. The core genes are distributed along the SI, apparently without a
      position effect.

PMID- 25580217
TI  - BiSpectral Index (BIS) monitoring may detect critical hypotension before
      automated non-invasive blood pressure (NIBP) measurement during general
      anaesthesia; a case report.
AB  - A patient undergoing general anaesthesia for neurosurgery exhibited an unexpected
      sudden decrease in the BiSpectral Index (BIS) value to near-zero. This prompted
      the detection of profound hypotension using non-invasive blood pressure (NIBP)
      measurement and expedited urgent assessment and treatment, with the patient
      making a full recovery. Widely regarded as a 'depth of anaesthesia' monitor, this
      case demonstrates the potential extra clinical benefit BIS may have in the
      detection of critical incidents such as anaphylaxis during general anaesthesia. 

PMID- 25580213
TI  - Biologically targeted probes for Zn2+: a diversity oriented modular "click-SNAr
      click" approach?Electronic supplementary information (ESI) available: Full
      experimental details including characterisation of all novel compounds can be
      found in the ESI. See DOI: 10.1039/c4sc01249f.
AB  - We describe a one-pot strategy for the high yielding, operationally simple
      synthesis of fluorescent probes for Zn2+ that bear biological targeting groups
      and exemplify the utility of our method through the preparation of a small
      library of sensors. Investigation of the fluorescence behaviour of our library
      revealed that although all behaved as expected in MeCN, under biologically
      relevant conditions in HEPES buffer, a plasma membrane targeting sensor displayed
      a dramatic switch on response to excess Zn2+ as a result of aggregation
      phenomena. Excitingly, in cellulo studies in mouse pancreatic islets demonstrated
      that this readily available sensor was indeed localised to the exterior of the
      plasma membrane and clearly responded to the Zn2+ co-released when the pancreatic
      beta cells were stimulated to release insulin. Conversely, sensors that target
      intracellular compartments were unaffected. These results demonstrate that this
      sensor has the potential to allow the real time study of insulin release from
      living cells and exemplifies the utility of our simple synthetic approach.

PMID- 25580219
TI  - Visualizing and quantifying movement from pre-recorded videos: The spectral time
      lapse (STL) algorithm.
AB  - When studying animal behaviour within an open environment, movement-related data
      are often important for behavioural analyses. Therefore, simple and efficient
      techniques are needed to present and analyze the data of such movements. However,
      it is challenging to present both spatial and temporal information of movements
      within a two-dimensional image representation. To address this challenge, we
      developed the spectral time-lapse (STL) algorithm that re-codes an animal's
      position at every time point with a time-specific color, and overlays it with a
      reference frame of the video, to produce a summary image. We additionally
      incorporated automated motion tracking, such that the animal's position can be
      extracted and summary statistics such as path length and duration can be
      calculated, as well as instantaneous velocity and acceleration. Here we describe
      the STL algorithm and offer a freely available MATLAB toolbox that implements the
      algorithm and allows for a large degree of end-user control and flexibility. 

PMID- 25580218
TI  - Ranking the quality of protein structure models using sidechain based network
      properties.
AB  - Determining the correct structure of a protein given its sequence still remains
      an arduous task with many researchers working towards this goal. Most structure
      prediction methodologies result in the generation of a large number of probable
      candidates with the final challenge being to select the best amongst these. In
      this work, we have used Protein Structure Networks of native and modeled proteins
      in combination with Support Vector Machines to estimate the quality of a protein
      structure model and finally to provide ranks for these models. Model ranking is
      performed using regression analysis and helps in model selection from a group of
      many similar and good quality structures. Our results show that structures with a
      rank greater than 16 exhibit native protein-like properties while those below 10
      are non-native like. The tool is also made available as a web-server (
      http://vishgraph.mbu.iisc.ernet.in/GraProStr/native_non_native_ranking.html),
      where, 5 modelled structures can be evaluated at a given time. 

PMID- 25580220
TI  - The second touch hypothesis: T cell activation, homing and polarization.
AB  - The second touch hypothesis states that T cell activation, proliferation,
      induction of homing receptors and polarization are distinguishable and, at least
      in part, sequential. The second touch hypothesis maintains that full T cell
      polarization requires T cell interaction with antigen-presenting cells (DCs,
      macrophages, B cells and certain activated stromal cells) in the non-lymphoid
      tissue where the antigen resides. Upon initial antigen encounter in peripheral
      lymph nodes (PLN), T cells become activated, proliferate and express homing
      receptors that enable them to recirculate to the (inflamed) tissue that contains
      the antigen. Differentiation into the T helper lineages Th1, Th2, Th17 and
      induced regulatory T cells (iTreg) requires additional antigen presentation by
      tissue macrophages and other antigen presenting cells (APCs) in the inflamed
      tissue. Here, I present a conceptual framework for the importance of peripheral
      (non-lymphoid) antigen presentation to antigen-experienced T cells. 

PMID- 25580221
TI  - The BioJS article collection of open source components for biological data
      visualisation.
AB  - Data-driven research has gained momentum in the life sciences. Visualisation of
      these data is essential for quick generation of hypotheses and their translation
      into useful knowledge. BioJS is a new proposed standard for JavaScript-based
      components to visualise biological data. BioJS is an open source community
      project that to date provides 39 different components contributed by a global
      community. Here, we present the BioJS F1000Research collection series. A total of
      12 components and a project status article are published in bulk. This collection
      does not intend to be an all-encompassing, comprehensive source of BioJS
      articles, but an initial set; future submissions from BioJS contributors are
      welcome. 

PMID- 25580222
TI  - Role of bacteriophages in STEC infections: new implications for the design of
      prophylactic and treatment approaches.
AB  - Shiga toxin (Stx) is considered the main virulence factor in Shiga toxin
      producing Escherichia coli (STEC) infections. Previously we reported the
      expression of biologically active Stx by eukaryotic cells in vitro and in vivo
      following transfection with plasmids encoding Stx under control of the native
      bacterial promoter. Since stx genes are present in the genome of lysogenic
      bacteriophages, here we evaluated the relevance of bacteriophages during STEC
      infection. We used the non-pathogenic E. coli K12 strain carrying a lysogenic
      933W mutant bacteriophage in which the stx operon was replaced by a gene encoding
      the green fluorescent protein (GFP). Tracking GFP expression using an In Vivo
      Imaging System (IVIS), we detected fluorescence in liver, kidney, and intestine
      of mice infected with the recombinant E. coli strain after treatment with
      ciprofloxacin, which induces the lytic replication and release of bacteriophages.
      In addition, we showed that chitosan, a linear polysaccharide composed of D
      glucosamine residues and with a number of commercial and biomedical uses, had
      strong anti-bacteriophage effects, as demonstrated in vitro and in vivo. These
      findings bring promising perspectives for the prevention and treatment of
      hemolytic uremic syndrome (HUS) cases. 

PMID- 25580223
TI  - Does the linear Sry transcript function as a ceRNA for miR-138? The sense of
      antisense.
AB  - Recently, the sex determining region Y ( Sry) and the cerebellar degeneration
      related protein 1 ( CDR1as) RNA transcripts have been described to function as a
      new class of post-transcriptional regulatory RNAs that behave as circular
      endogenous RNA sponges for the micro RNAs (miRNAs) miR-138 and miR-7,
      respectively. A special feature of the Sry gene is its ability to generate linear
      and circular transcripts, both transcribed in the sense orientation. Here we
      remark that both sense (e.g. Sry RNA) and antisense (e.g. CDR1as) transcripts
      could circularize and behave as miRNAs sponges, and importantly, that also
      protein-coding segments of mRNAs could also assume this role. Thus, it is
      reasonable to think that the linear Sry sense transcript could additionally act
      as a miRNA sponge, or as an endogenous competing RNA for miR-138. 

PMID- 25580224
TI  - The Cytoscape app article collection.
AB  - As a network visualization and analysis platform, Cytoscape relies on apps to
      provide domain-specific features and functions. There are many resources
      available to support Cytoscape app development and distribution, including the
      Cytoscape App Store and an online "cookbook" for app developers. This article
      collection is another resource to help researchers find out more about relevant
      Cytoscape apps and to provide app developers with useful implementation tips. The
      collection will grow over time as new Cytoscape apps are developed and published.

PMID- 25580225
TI  - Why are neurotransmitters neurotoxic? An evolutionary perspective.
AB  - In the CNS, minor changes in the concentration of neurotransmitters such as
      glutamate or dopamine can lead to neurodegenerative diseases. We present an
      evolutionary perspective on the function of neurotransmitter toxicity in the CNS.
      We hypothesize that neurotransmitters are selected because of their toxicity,
      which serves as a test of neuron quality and facilitates the selection of
      neuronal pathways. This perspective may offer additional explanations for the
      reduction of neurotransmitter concentration in the CNS with age, and suggest an
      additional role for the blood-brain barrier. It may also suggest a connection
      between the specific toxicity of the neurotransmitters released in a specific
      region of the CNS, and elucidate their role as chemicals that are optimal for
      testing the quality of cells in that region. 

PMID- 25580226
TI  - The ACCE method: an approach for obtaining quantitative or qualitative estimates
      of residual confounding.
AB  - BACKGROUND:   Nonrandomized studies typically cannot account for confounding from
      unmeasured factors.  METHOD:   A method is presented that exploits the recently
      identified phenomenon of  "confounding amplification" to produce, in principle, a
      quantitative estimate of total residual confounding resulting from both measured
      and unmeasured factors.  Two nested propensity score models are constructed that
      differ only in the deliberate introduction of an additional variable(s) that
      substantially predicts treatment exposure.  Residual confounding is then
      estimated by dividing the change in treatment effect estimate between models by
      the degree of confounding amplification estimated to occur, adjusting for any
      association between the additional variable(s) and outcome. RESULTS:   A
      hypothetical example is provided to illustrate how the method produces a
      quantitative estimate of residual confounding if the method's requirements and
      assumptions are met.  Previously published data is used to illustrate that,
      whether or not the method routinely provides precise quantitative estimates of
      residual confounding, the method appears to produce a valuable qualitative
      estimate of the likely direction and general size of residual confounding.
      LIMITATIONS:   Uncertainties exist, including identifying the best approaches
      for: 1) predicting the amount of confounding amplification, 2) minimizing changes
      between the nested models unrelated to confounding amplification, 3) assessing
      the association of the introduced variable(s) with outcome, and 4) deriving
      confidence intervals for the method's estimates (although bootstrapping is one
      plausible approach). CONCLUSIONS:   To this author's knowledge, it has not been
      previously suggested that the phenomenon of confounding amplification, if such
      amplification is as predictable as suggested by a recent simulation, provides a
      logical basis for estimating total residual confounding. The method's basic
      approach is straightforward.  The method's routine usefulness, however, has not
      yet been established, nor has the method been fully validated. Rapid further
      investigation of this novel method is clearly indicated, given the potential
      value of its quantitative or qualitative output.

PMID- 25580227
TI  - Biology and conservation of elasmobranchs: an introduction to the collection.
AB  - Elasmobranchs, the taxonomic group comprising sharks, skates and rays, play
      important roles in society and marine ecology but several species in this
      subclass are under threat.  This collection aims to be an open access hub for
      articles concerning all areas of elasmobranch biology and conservation. The
      collection is indefinitely open to further submissions and so will continue to
      grow as additional articles are added. 

PMID- 25580228
TI  - Stress, rejection, and hormones: Cortisol and progesterone reactivity to
      laboratory speech and rejection tasks in women and men.
AB  - Stress and social rejection have important impacts on health. Among the
      mechanisms implicated are hormonal systems such as the hypothalamic-pituitary
      adrenal (HPA) axis, which produces cortisol in humans. Current research employs
      speech stressors and social rejection stressors to understand hormonal responses
      in a laboratory setting. However, it is not clear whether social rejection
      stressors elicit hormonal reactivity. In addition to cortisol, progesterone has
      been highlighted as a potential stress- and affiliation-related hormone in
      humans. In the present study, 131 participants (70 men and 61 women) were
      randomly assigned to be exposed to one of four conditions: standardized speech
      stressor; speech control; social rejection task; or a control (inclusion) version
      of the social rejection task. Saliva samples were collected throughout the study
      to measure cortisol and progesterone. As hypothesized, we found the expected
      increase in cortisol in the speech stressor, and we also found that the social
      rejection task did not increase cortisol, underscoring the divergence between
      unpleasant experiences and HPA axis activity. However, we did not find evidence
      for progesterone increase either during the speech- or social rejection tasks.
      Compared with past studies on progesterone and stress in humans, the present
      findings present a mixed picture. Future work is needed to delineate the contexts
      and types of manipulations which lead to progesterone increases in humans. 

PMID- 25580229
TI  - The F1000Research Antibody Validation Article Collection.
AB  - Well validated antibodies are crucial to progress in a wide range of life science
      disciplines, but validating an antibody is a complex and ongoing process.
      Antibody validation is often carried out as preliminary work to a larger study so
      the validation data may go unpublished and needless duplication of efforts can
      occur. This collection of articles in F1000Research provides a home for papers
      describing antibody validation studies. Our goal is to encourage publishing of
      all independent studies, both positive and negative, which increase understanding
      of how antibodies perform. These could range from large studies with thousands of
      antibodies to small single figure studies which validate an individual antibody
      for a specific purpose. Opinion or Correspondence articles considering any aspect
      of antibody validation are also welcome. Here, we provide an introduction to the
      collection which we hope will grow and become a valuable resource for the many
      thousands of researchers who use antibodies. 

PMID- 25580231
TI  - Collecting rare diseases.
AB  - This editorial introduces the F1000Research rare disease collection. It is common
      knowledge that for new treatments to be successful there has to be a partnership
      between the many interested parties such as the patient, advocate, disease
      foundations, the academic scientists, venture funding organizations, biotech
      companies, pharmaceutical companies, NIH, and the FDA. Our intention is to
      provide a forum for discussion and dissemination of any rare disease related
      topics that will advance scientific understanding and progress to treatments. 

PMID- 25580232
TI  - Working towards a consensus for antibody validation.
AB  - Commercial research antibodies are the most commonly used product in the life
      science tools market, and their applications represent a significant investment
      of time and resources for researchers. Frequently however, the quality of
      antibodies does not meet the expectations of consumers, causing loss of valuable
      time and money. This can delay research efforts and scientific discovery, or even
      lead to false, irreproducible results to be published in the scientific
      literature. This raises the question of whether there should be universal
      standards for validating antibodies.   During the 1 (st) International Antibody
      Validation Forum, hosted by St John's Laboratory Ltd on October 15 (th) 2014 at
      Queen Mary University of London, scientists from academia and industry presented
      data highlighting quality issues arising from lack of antibody validation. While
      the forum identified significant current problems in the antibody market, it also
      discussed future opportunities for improved quality and transparency by
      encouraging data disclosure and data sharing. This article highlights the key
      issues and conclusions reached at the forum. 

PMID- 25580233
TI  - The F1000Research: Ebola article collection.
AB  - The explosion of information about Ebola requires rapid publication, transparent
      verification and unrestricted access. I urge everyone involved in all aspects of
      the Ebola epidemic to openly and rapidly report their experiences and findings. 

PMID- 25580230
TI  - Metabolomics in psoriatic disease: pilot study reveals metabolite differences in
      psoriasis and psoriatic arthritis.
AB  - IMPORTANCE: While "omics" studies have advanced our understanding of inflammatory
      skin diseases, metabolomics is mostly an unexplored field in dermatology.
      OBJECTIVE: We sought to elucidate the pathogenesis of psoriatic diseases by
      determining the differences in metabolomic profiles among psoriasis patients with
      or without psoriatic arthritis and healthy controls. DESIGN: We employed a global
      metabolomics approach to compare circulating metabolites from patients with
      psoriasis, psoriasis and psoriatic arthritis, and healthy controls. SETTING:
      Study participants were recruited from the general community and from the
      Psoriasis Clinic at the University of California Davis in United States.
      PARTICIPANTS: We examined metabolomic profiles using blood serum samples from 30
      patients age and gender matched into three groups: 10 patients with psoriasis, 10
      patients with psoriasis and psoriatic arthritis and 10 control participants. Main
      outcome(s) and measures(s): Metabolite levels were measured calculating the mean
      peak intensities from gas chromatography time-of-flight mass spectrometry.
      RESULTS: Multivariate analyses of metabolomics profiles revealed altered serum
      metabolites among the study population. Compared to control patients, psoriasis
      patients had a higher level of alpha ketoglutaric acid (Pso: 288 +/- 88; CONTROL:
      209 +/- 69; p=0.03), a lower level of asparagine (Pso: 5460 +/- 980; CONTROL:
      7260 +/- 2100; p=0.02), and a lower level of glutamine (Pso: 86000 +/- 20000;
      CONTROL: 111000 +/- 27000; p=0.02). Compared to control patients, patients with
      psoriasis and psoriatic arthritis had increased levels of glucuronic acid (Pso +
      PsA: 638 +/- 250; CONTROL: 347 +/- 61; p=0.001). Compared to patients with
      psoriasis alone, patients with both psoriasis and psoriatic arthritis had a
      decreased level of alpha ketoglutaric acid (Pso + PsA: 186 +/- 80; Pso: 288 +/-
      88; p=0.02) and an increased level of lignoceric acid (Pso + PsA: 442 +/- 280;
      Pso: 214 +/- 64; p=0.02). CONCLUSIONS AND RELEVANCE: The metabolite differences
      help elucidate the pathogenesis of psoriasis and psoriatic arthritis and they may
      provide insights for therapeutic development.

PMID- 25580234
TI  - F1000Research: Tics welcomes you to 21st century biomedical publishing.
AB  - Tics are repeated, usually suppressible movements or vocalizations. They are the
      defining features of tic disorders including Tourette syndrome, but many people
      have them for shorter durations at some point in childhood. This editorial marks
      the beginning of the F1000RESEARCH: Tics specialty section, an effort to provide
      a single portal to modern research on tics and tic disorders. Publications in
      F1000RESEARCH: Tics benefit from F1000RESEARCH's novel approach to publishing, in
      which articles can be published within days of submission. Peer review happens
      after publication and is fully open. When the submitted article or a revision is
      approved, it is promptly submitted to repositories including NIH's PubMed
      Central. In addition to research articles and reviews, F1000RESEARCH: Tics will
      publish study protocols, clinical practice articles, case reports, and data
      notes. The home page will also provide links to expert recommendations of
      articles that have appeared elsewhere, and to relevant posters from scientific
      meetings (http://f1000.com/posters/). F1000RESEARCH's approach is enabled by the
      capabilities of internet publication, including space to publish the full results
      of a study rather than just a few graphs selected from the data. Publishing
      methodologically sound studies without requiring subjective editorial judgments
      of novelty or broad appeal brings numerous advantages, including minimizing
      publication bias and shining the light of openness on peer review. To celebrate
      the launch of the Tics section, F1000RESEARCH is offering discounted article
      processing charges for manuscripts submitted by March 1st 2015. I have had good
      experiences publishing in F1000RESEARCH, and look forward to seeing a wide range
      of tic-related manuscripts submitted. 

PMID- 25580235
TI  - Timing is everything: a collection on how clocks affect resilience in biological
      systems.
AB  - Why do some people get sick, and others do not? This basic question, of
      vulnerability and resilience, is of crucial importance in physical and mental
      health research. Determining factors that impart resilience, or contribute to
      vulnerability, could be a turning point in our fundamental understanding of
      disease. This collection explores current data on the role of two systems that
      seem indispensible for health: Circadian rhythms, and Sleep. While we have
      learned a great deal about the mechanisms that control these two biological
      processes, we are only at the beginning of our understanding of how these systems
      impact mood, cognition, immune function, and metabolism. The concepts of
      resilience and vulnerability may be useful in understanding the myriad effects of
      circadian rhythm and sleep disruption on mental and physical health, and perhaps
      provide new insights to how we can predict - and protect against - negative
      outcomes while amplifying positive health effects. 

PMID- 25580236
TI  - Neural-mesodermal progenitor interactions in pattern formation: an introduction
      to the collection.
AB  - Mesodermal and spinal cord progenitors originate from common founder cells from
      which they segregate during development. Moreover, neural and mesodermal tissues
      closely interact during embryogenesis to ensure timely patterning and
      differentiation of both head and trunk structures. For instance, the fate and
      morphogenesis of neural progenitors is dependent on signals produced by
      mesodermal cells and vice-versa. While some of the cellular and molecular signals
      that mediate these interactions have been described, much more remains to be
      uncovered. The scope of this collection will cover these interactions between
      neural (CNS or PNS) and mesodermal progenitors in patterning body plans and
      specific body systems in vertebrate embryos. This includes, but is not limited
      to, interactions influencing the formation of body axes, neural tube formation,
      neural crest migration, gut development, muscle patterning and myogenesis. 

PMID- 25580237
TI  - Active learning and decision making: an introduction to the collection.
AB  - The importance of exploratory behaviors by which agents actively sample
      information has been long appreciated in a range of disciplines. However, because
      of their complexity and cognitive nature, these behaviors have been difficult to
      characterize. In recent years, a resurgence of interest in this question has been
      based on a confluence of ideas from multiple fields, including machine learning,
      development, perceptual learning and attention and decision making.  This
      collection of articles in F1000Research aims to provide a home for a broad range
      of studies addressing this topic. We welcome full length research articles, brief
      communications, single figure studies, and review/opinion articles, and studies
      using computational, behavioral or neural approaches.  Here, we provide an
      introduction to the collection which we hope will grow and become a valuable
      resource for the researchers exploring this topic. 

PMID- 25580238
TI  - Ion channels in somatosensory transmission: an introduction to the collection.
AB  - Excitation of peripheral endings of sensory nerves is a primary event in most
      types of somatosensation, including pain. This excitation and transmission of
      action potentials within somatosensory pathways is brought about by the concerted
      action of the wide array of plasmalemmal ion channels, some of which are specific
      to somatosensory nerves. Accordingly, ion channel deficiencies or
      'channelopathies' often underlie sensory disorders and pathological pain states
      and many current and prospective analgesics target ion channels. This
      F1000Research article collection is focused on the current advances in
      understanding function and regulation of ion channels controlling excitability
      and synaptic transmission within somatosensory pathways. The focus is on the
      peripheral neurons but studies of central mechanisms that integrate peripheral
      inputs are also welcome. We also welcome discussions of emerging approaches,
      methods and techniques in somatosensory physiology. 

PMID- 25580239
TI  - On data sharing in computational drug discovery and the need for data notes.
AB  - In the big data era, the scientific community is in need of better practices and
      infrastructures for data deposition and sharing. In addition, scientific journals
      are challenged with formulating, implementing, and enforcing commonly accepted
      data deposition guidelines and addressing problems associated with the use of
      proprietary data. Furthermore, new publication formats are required to
      specifically focus on data, their organization, and related issues and raise
      awareness of data heterogeneity and complexity. Such types of publications should
      also present a forum for evaluating and discussing specifics of data upon which
      follow-up investigations are based. Data articles/notes introduced by
      F1000Research represent an important step in the right direction. 

PMID- 25580240
TI  - The Global Virus Network's testimony on Ebola to the U.S. Senate.
AB  - In this Editorial I briefly outline the Global Virus Network's testimony to the
      recent U.S. Senate's "Fighting Ebola and Protecting America" committee hearing. 

PMID- 25580242
TI  - Click chemistry facilitates direct labelling and super-resolution imaging of
      nucleic acids and proteins?Electronic supplementary information (ESI) available.
      See DOI: 10.1039/c4ra01027bClick here for additional data file.
AB  - We demonstrate high-density labelling of cellular DNA and RNA using click
      chemistry and perform confocal and super-resolution microscopy. We visualize the
      crescent and ring-like structure of densely packed RNA in nucleoli. We further
      demonstrate click chemistry with unnatural amino acids for super-resolution
      imaging of outer-membrane proteins of E. coli.

PMID- 25580243
TI  - Continuous release of gentamicin from gold nanocarriers.
AB  - Antibiotics are still the most effective agents used to fight bacterial
      infections. Antibiotics are quickly metabolised or excreted from the human body,
      thus they need to be frequently administered (a few times a day) and their half
      life is usually an important factor in the therapeutic choice. In order to render
      the administration less frequent, antibiotic release from a carrier can be
      employed. In this work we covalently bound gentamicin to gold nanoparticles
      capped with cysteine or glutathione as gold nanoparticles are biologically safe.
      The conjugates exhibited antimicrobial activity against both S. aureus and MRSA
      at concentrations as low as 0.1 mg NP per ml consistent with an antibiotic load
      of 1-2% w/w as determined through TGA. No antimicrobial activity was exhibited by
      the unconjugated nanoparticles. The release of gentamicin from the conjugates was
      monitor in buffer solutions at pH = 7 and the antibiotic concentration continued
      to increase over two days. This work demonstrates that gold nanoparticles can be
      employed as antibiotic carriers providing a continuous release of antibiotic over
      a few days. Glutathione appeared to be a better coupling agent than cysteine
      allowing a higher load of gentamicin resulting in lower inhibitory concentrations
      of the conjugates.

PMID- 25580241
TI  - The role of biocatalysis in the asymmetric synthesis of alkaloids.
AB  - Alkaloids are not only one of the most intensively studied classes of natural
      products, their wide spectrum of pharmacological activities also makes them
      indispensable drug ingredients in both traditional and modern medicine. Among the
      methods for their production, biotechnological approaches are gaining importance,
      and biocatalysis has emerged as an essential tool in this context. A number of
      chemo-enzymatic strategies for alkaloid synthesis have been developed over the
      years, in which the biotransformations nowadays take an increasingly 'central'
      role. This review summarises different applications of biocatalysis in the
      asymmetric synthesis of alkaloids and discusses how recent developments and novel
      enzymes render innovative and efficient chemo-enzymatic production routes
      possible.

PMID- 25580244
TI  - Synthesis and Catalytic Activity of Pluronic Stabilized Silver-Gold Bimetallic
      Nanoparticles.
AB  - In this report, we demonstrate a rapid, simple, and green method for synthesizing
      silver-gold (Ag-Au) bimetallic nanoparticles (BNPs). We used a novel modification
      to the galvanic replacement reaction by suspending maltose coated silver
      nanoparticles (NPs) in ~ 2% aqueous solution of EO100PO65EO100 (Pluronic F127)
      prior to HAuCl4 addition. The Pluronic F127 stabilizes the BNPs, imparts
      biocompatibility, and mitigates the toxicity issues associated with other
      surfactant stabilizers. BNPs with higher Au:Ag ratios and, subsequently,
      different morphologies were successfully synthesized by increasing the
      concentration of gold salt added to the Ag NP seeds. These BNPs have enhanced
      catalytic activities than typically reported for monometallic Au or Ag NPs (~ 2
      10 fold) of comparable sizes in the sodium borohydride reduction of 4
      nitrophenol. The 4-nitrophenol reduction rates were highest for partially hollow
      BNP morphologies.

PMID- 25580246
TI  - Photo-triggerable Hydrogel-Nanoparticle Hybrid Scaffolds for Remotely Controlled
      Drug Delivery.
AB  - Remotely-triggerable drug delivery systems enable the user to adjust dosing
      regimens on-demand based on a patient's physiological response and clinical
      needs. However, currently reported systems are limited by the non-specific
      leakage of drugs in the absence of triggering and the lack of repeatability over
      multiple cycles of release. To this end, we have designed a unique hydrogel
      nanoparticle hybrid scaffold that provides a chemically-defined, remotely
      triggerable and on-demand release of small molecule drugs. Our hybrid platform
      consists of three distinct components: 1) a photo-triggerable chemical compound,
      which serves to release a covalently-bound drug upon photo-irradiation, 2) a
      nanoparticle, which serves to covalently bind the photo-triggerable compound, and
      3) a polymeric hydrogel, which serves to hold the drug-conjugated nanoparticle.
      Upon photo-irradiation, the activation of the photo-triggerable compound is
      designed to initiate a series of intramolecular chemical rearrangements, which
      would cleave the covalently-bound drug and release it from the hydrogel. The
      combination of these distinct components in a single scaffold proved to be an
      effective drug delivery system, as demonstrated by the delivery of a model drug
      to a malignant cancer line. Our hybrid scaffold can be easily tuned for
      practically any biological application of interest, thus offering immense
      potential for clinical therapies.

PMID- 25580245
TI  - Bacteria repelling poly(methylmethacrylate-co-dimethylacrylamide) coatings for
      biomedical devices?Electronic supplementary information (ESI) available: Polymer
      microarray screening, including analysis of bacterial adhesion by fluorescence
      microscopy and SEM, and chemical composition of bacteria repelling polymers
      identified in the screen; polymer synthesis and characterisation; preparation of
      catheter pieces and solvent studies, and details for confocal imaging/analysis.
      See DOI: 10.1039/c4tb01129eClick here for additional data file.
AB  - Nosocomial infections due to bacteria have serious implications on the health and
      recovery of patients in a variety of medical scenarios. Since bacterial
      contamination on medical devices contributes to the majority of nosocomical
      infections, there is a need for redesigning the surfaces of medical devices, such
      as catheters and tracheal tubes, to resist the binding of bacteria. In this work,
      polyurethanes and polyacrylates/acrylamides, which resist binding by the major
      bacterial pathogens underpinning implant-associated infections, were identified
      using high-throughput polymer microarrays. Subsequently, two 'hit' polymers, PA13
      (poly(methylmethacrylate-co-dimethylacrylamide)) and PA515
      (poly(methoxyethylmethacrylate-co-diethylaminoethylacrylate-co
      methylmethacrylate)), were used to coat catheters and substantially shown to
      decrease binding of a variety of bacteria (including isolates from infected
      endotracheal tubes and heart valves from intensive care unit patients). Catheters
      coated with polymer PA13 showed up to 96% reduction in bacteria binding in
      comparison to uncoated catheters.

PMID- 25580247
TI  - Development of Injectable Citrate-Based Bioadhesive Bone Implants.
AB  - Injectable bone implants have been widely used in bone tissue repairs including
      the treatment of comminuted bone fractures (CBF). However, most injectable bone
      implants are not suitable for the treatment of CBF due to their weak tissue
      adhesion strengths and minimal osteoinduction. Citrate has been recently reported
      to promote bone formation through enhanced bioceramic integration and
      osteoinductivity. Herein, a novel injectable citrate-based mussel-inspired
      bioadhesive hydroxyapatite (iCMBA/HA) bone substitute was developed for CBF
      treatment. iCMBA/HA can be set within 2-4 minutes and the as-prepared (wet)
      iCMBA/HA possess low swelling ratios, compressive mechanical strengths of up to
      3.2+/-0.27 MPa, complete degradation in 30 days, suitable biocompatibility, and
      osteoinductivity. This is also the first time to demonstrate that citrate
      supplementation in osteogenic medium and citrate released from iCMBA/HA
      degradation can promote the mineralization of osteoblastic committed human
      mesenchymal stem cells (hMSCs). In vivo evaluation of iCMBA/HA in a rabbit
      comminuted radial fracture model showed significantly increased bone formation
      with markedly enhanced three-point bending strength compared to the negative
      control. Neovascularization and bone ingrowth as well as highly organized bone
      formation were also observed showing the potential of iCMBA/HA in treating CBF.

PMID- 25580248
TI  - Tri-peptide cationic lipids for gene delivery.
AB  - Several novel tri-peptide cationic lipids were designed and synthesized for
      delivering DNA and siRNA. They have tri-lysine and tri-ornithine as head groups,
      carbamate group as linker and 12 and 14 carbon atom alkyl groups as tails. These
      tri-peptide cationic lipids were prepared into cationic liposomes for the study
      of the physicochemical properties and gene delivery. Their particle size, Zeta
      potential and DNA-binding were characterized to show that they were suitable for
      gene transfection. The further results indicate that these lipids can transfer
      DNA and siRNA very efficiently into NCI-H460 and Hep-2 tumor cells. The selected
      lipid, CDO14, was able to deliver combined siRNAs against c-Myc and VEGF for
      silencing distinct oncogenic pathways in lung tumors of mice, with little in
      vitro and in vivo toxicity.

PMID- 25580249
TI  - Photoactive rolled-up TiO2 microtubes: fabrication, characterization and
      applications?Electronic supplementary information (ESI) available. See DOI:
      10.1039/c4tc00796dClick here for additional data file.
AB  - Because of its unique properties, titania (TiO2) represents a promising candidate
      in a wide variety of research fields. In this paper, some of the properties and
      potential applications of titania within rolled-up nanotechnology are explored.
      It is shown how the structural and optical properties of rolled titania
      microtubes can be controlled by properly tuning the microfabrication parameters.
      The rolling up of titania films on different sacrificial layers and containing
      different shapes, achieving a control on the diameter of the fabricated titania
      microtubes, is presented. In order to obtain the more photoactive crystalline
      form of titania, one during-fabrication and two post-fabrication methods are
      demonstrated. Interesting applications in the fields of photocatalysis and
      photonics are suggested: the use of titania rolled-up microtubes as micromotors
      and optical microresonators is presented.

PMID- 25580250
TI  - Ionothermal synthesis of open-framework metal phosphates with a Kagome lattice
      network exhibiting canted anti-ferromagnetism?Electronic supplementary
      information (ESI) available: Cif files, atomic parameters, X-ray diffraction
      patterns, IR spectra, TG curves, and thermal ellipsoid plot and atomic label
      schemes of compound 1-4. See DOI: 10.1039/c4tc00290cClick here for additional
      data file.
AB  - Four open-framework transition-metal phosphates; (NH4)2Co3(HPO4)2F4 (1),
      (NH4)Co3(HPO4)2(H2PO4)F2 (2), KCo3(HPO4)2(H2PO4)F2 (3), and KFe3(HPO4)2(H2PO4)F2
      (4); are prepared by ionothermal synthesis using pyridinium hexafluorophosphate
      as the ionic liquid. Single-crystal X-ray diffraction analyses reveal that the
      four compounds contain cobalt/iron-oxygen/fluoride layers with Kagome topology
      composed of interlinked face-sharing MO3F3/MO4F2 octahedra. PO3OH pseudo
      tetrahedral groups augment the [M3O6F4] (1)/[M3O8F2] layers on both sides to give
      M3(HPO4)2F4 (1) and M3(HPO4)2F2 (2-4) layers. These layers are stacked along the
      a axis in a sequence AA..., resulting in the formation of a layer structure for
      (NH4)2Co3(HPO4)2F4(1). In NH4Co3(HPO4)2(H2PO4)F2 and KM3(HPO4)2(H2PO4)F2, the
      M3(HPO4)2F2 layers are stacked along the a axis in a sequence AA i ... and are
      connected by [PO3(OH)] tetrahedra, giving rise to a 3-D open framework structure
      with 10-ring channels along the [001] direction. The negative charges of the
      inorganic framework are balanced by K+/NH4+ ions located within the channels. The
      magnetic transition metal cations themselves form layers with stair-case Kagome
      topology. Magnetic susceptibility and magnetization measurements reveal that all
      four compounds exhibit a canted anti-ferromagnetic ground state (Tc = 10 or 13 K
      for Co and Tc = 27 K for Fe) with different canting angles. The full orbital
      moment is observed for both Co2+ and Fe2+.

PMID- 25580251
TI  - MyD88: a central player in innate immune signaling.
AB  - MyD88 is the canonical adaptor for inflammatory signaling pathways downstream of
      members of the Toll-like receptor (TLR) and interleukin-1 (IL-1) receptor
      families. MyD88 links IL-1 receptor (IL-1R) or TLR family members to IL-1R
      associated kinase (IRAK) family kinases via homotypic protein-protein
      interaction. Activation of IRAK family kinases leads to a variety of functional
      outputs, including the activation of nuclear factor-kappa B (NFkappaB), mitogen
      activated protein kinases, and activator protein 1, making MyD88 a central node
      of inflammatory pathways. As more details of MyD88-dependent signaling have been
      elucidated, it has become clear that the functions of this critical signaling
      component can be influenced by multiple interaction partners in distinct
      subcellular compartments. In this review, we will focus on recent developments in
      the understanding of the assembly of MyD88 signaling complexes and the mechanisms
      leading to the diversification of MyD88-based signaling. 

PMID- 25580253
TI  - Transgenerational acclimation of fishes to climate change and ocean
      acidification.
AB  - There is growing concern about the impacts of climate change and ocean
      acidification on marine organisms and ecosystems, yet the potential for
      acclimation and adaptation to these threats is poorly understood. Whereas many
      short-term experiments report negative biological effects of ocean warming and
      acidification, new studies show that some marine species have the capacity to
      acclimate to warmer and more acidic environments across generations.
      Consequently, transgenerational plasticity may be a powerful mechanism by which
      populations of some species will be able to adjust to projected climate change.
      Here, I review recent advances in understanding transgenerational acclimation in
      fishes. Research over the past 2 to 3 years shows that transgenerational
      acclimation can partially or fully ameliorate negative effects of warming,
      acidification, and hypoxia in a range of different species. The molecular and
      cellular pathways underpinning transgenerational acclimation are currently
      unknown, but modern genetic methods provide the tools to explore these
      mechanisms. Despite the potential benefits of transgenerational acclimation,
      there could be limitations to the phenotypic traits that respond
      transgenerationally, and trade-offs between life stages, that need to be
      investigated. Future studies should also test the potential interactions between
      transgenerational plasticity and genetic evolution to determine how these two
      processes will shape adaptive responses to environmental change over coming
      decades. 

PMID- 25580252
TI  - Mechanisms of planar cell polarity establishment in Drosophila.
AB  - Correct patterning and polarization of epithelial and mesenchymal cells are
      essential for morphogenesis and function of all organs and organisms. Epithelial
      cells are generally polarized in two axes: (a) the ubiquitous apical-basal axis
      and (b) polarity within the plane of the epithelium. The latter is generally
      referred to as planar cell polarity (PCP) and also is found in several contexts
      of mesenchymal cell patterning. In Drosophila, all adult structures display PCP
      features, and two conserved molecular systems (the Fat [Ft]/Dachsous [Ds] system
      and the Frizzled [Fz]/PCP pathway) that regulate this process have been
      identified. Although significant progress has been made in dissecting aspects of
      PCP signaling within cells, much remains to be discovered about the mechanisms of
      long-range and local PCP cell-cell interactions. Here, we discuss the current
      models based on Drosophila studies and incorporate recent insights into this long
      standing cell and developmental biology problem. 

PMID- 25580255
TI  - Recent advances in understanding/management of hypospadias.
AB  - Hypospadias is the second most common birth anomaly, affecting 1 of every 300
      males. The abnormal position of the urinary opening, and associated downward
      curvature of the penis in some cases, potentially impact both urinary and sexual
      function. Modern surgical correction most often involves tubularization of the
      urethral plate, those tissues which normally should have completed urethral
      development. This article discusses recent progress in hypospadias repair.
      Prospective data collection in consecutive patients promotes better understanding
      of both patient and technical factors that influence surgical complications.
      Patients with a proximal urinary opening near or within the scrotum, those
      failing prior to repairs, and/or those with a small glans diameter have increased
      likelihood for urethroplasty complications. Quality review of reliable data led
      to two layer urethroplasty covered with tunica vaginalis in proximal repairs,
      significantly reducing postoperative fistulas. Neither preoperative androgens
      used to grow a small diameter glans, nor a change in sutures used to approximate
      the glans wings reduced wound dehiscence, but a recent technical modification of
      the glansplasty with more extensive dissection before suturing has. The
      observation that reoperation increases risk for further complications three-fold
      suggests the less common proximal repairs and reoperations should be
      subspecialized so that designated surgeons can gain greater expertise. In
      addition, surgeons performing hypospadias repair must better define the
      complications that occur so that scientific reporting of outcomes becomes more
      standardized. Standardized objective means to assess results are also needed so
      that surgeons performing different repairs can compare outcomes. 

PMID- 25580254
TI  - Research priorities for the development and implementation of serological tools
      for malaria surveillance.
AB  - Surveillance is a key component of control and elimination programs. Malaria
      surveillance has been typically reliant on case reporting by health services,
      entomological estimates and parasitemia (Plasmodium species) point prevalence.
      However, these techniques become less sensitive and relatively costly as
      transmission declines. There is great potential for the development and
      application of serological biomarkers of malaria exposure as sero-surveillance
      tools to strengthen malaria control and elimination. Antibodies to malaria
      antigens are sensitive biomarkers of population-level malaria exposure and can be
      used to identify hotspots of malaria transmission, estimate transmission levels,
      monitor changes over time or the impact of interventions on transmission, confirm
      malaria elimination, and monitor re-emergence of malaria. Sero-surveillance tools
      could be used in reference laboratories or developed as simple point-of-care
      tests for community-based surveillance, and different applications and target
      populations dictate the technical performance required from assays that are
      determined by properties of antigens and antibody responses. To advance the
      development of sero-surveillance tools for malaria elimination, major gaps in our
      knowledge need to be addressed through further research. These include greater
      knowledge of potential antigens, the sensitivity and specificity of antibody
      responses, and the longevity of these responses and defining antigens and
      antibodies that differentiate between exposure to Plasmodium falciparum and P.
      vivax. Additionally, a better understanding of the influence of host factors,
      such as age, genetics, and comorbidities on antibody responses in different
      populations is needed. 

PMID- 25580256
TI  - Novel therapies for open-angle glaucoma.
AB  - Open-angle glaucoma is a multifactorial optic neuropathy characterized by
      progressive loss of retinal ganglion cells and their axons. It is an irreversible
      disease with no established cure. The only currently approved treatment is aimed
      at lowering intraocular pressure, the most significant risk factor known to date.
      However, it is now clear that there are other risk factors involved in glaucoma's
      pathophysiology. To achieve future improvements in glaucoma management, new
      approaches to therapies and novel targets must be developed. Such therapies may
      include new tissue targets for lowering intraocular pressure, molecules
      influencing ocular hemodynamics, and treatments providing neuroprotection of
      retinal ganglion cells. Furthermore, novel drug delivery systems are in
      development that may improve patient compliance, increase bioavailability, and
      decrease adverse side effects. 

PMID- 25580258
TI  - Antibiotic prophylaxis and reflux: critical review and assessment.
AB  - The use of continuous antibiotic prophylaxis (CAP) was critical in the evolution
      of vesicoureteral reflux (VUR) from a condition in which surgery was the standard
      of treatment to its becoming a medically managed condition. The efficacy of
      antibiotic prophylaxis in the management of VUR has been challenged in recent
      years, and significant confusion exists as to its clinical value. This review
      summarizes the critical factors in the history, use, and investigation of
      antibiotic prophylaxis in VUR. This review provides suggestions for assessing the
      potential clinical utility of prophylaxis. 

PMID- 25580259
TI  - Transfusion medicine as of 2014.
AB  - Transfusion of blood components is one of the most common medical treatments, and
      in spite of the time that has evolved since we started to transfuse blood
      routinely in the 1930s, there are issues associated with its use that we are
      still trying to improve. Issues such as when to transfuse and adverse effects
      associated with the transfusion are fields where new evidence is being generated
      that ideally should help us to indicate when and what to transfuse to the
      patients. The recognition that the evidence generated in randomized control
      trials was not widely applied to guide the indication of the transfusion of blood
      components has provoked the development of initiatives that try to reduce its
      unnecessary usage. Those initiatives, grouped under the name of patient blood
      management, have represented a significant paradigm change, and a growing number
      of activities in this field are performed in health-care facilities around the
      world. This article tries to summarize the latest publications in those fields. 

PMID- 25580257
TI  - Recent advances in the management of acute bronchiolitis.
AB  - Acute bronchiolitis is characterized by acute wheezing in infants or children and
      is associated with signs or symptoms of respiratory infection; it is rarely
      symptomatic in adults and the most common etiologic agent is respiratory
      syncytial virus (RSV). Usually it does not require investigation, treatment is
      merely supportive and a conservative approach seems adequate in the majority of
      children, especially for the youngest ones (<3 months); however, clinical scoring
      systems have been proposed and admission in hospital should be arranged in case
      of severe disease or a very young age or important comorbidities. Apnea is a very
      important aspect of the management of young infants with bronchiolitis. This
      review focuses on the clinical, radiographic, and pathologic characteristics, as
      well as the recent advances in management of acute bronchiolitis. 

PMID- 25580260
TI  - Advances in the management of enuresis.
AB  - There are still many undiscovered facts about enuresis, even though it is a very
      old "symptom". It is a significant health problem with a high prevalence among
      children and a lower prevalence in adulthood. Many treatment guidelines have been
      proposed for the management of this problem. The improvement of diagnostic tools,
      and also treatment modalities, have had a significant impact on success rates;
      however, the long-term success rates need to be higher, especially in resistant
      cases. In this report, we summarize the advances made in the diagnosis and
      treatment of enuresis. 

PMID- 25580261
TI  - Mycobacterium abscessus subsp abscessus lung disease: 'trouble ahead, trouble
      behind...'.
AB  - Mycobacterium abscessus subsp abscessus is the most common respiratory pathogen
      among the rapidly growing non-tuberculous mycobacteria (NTM) and is also the most
      feared due to its well-deserved reputation for being refractory to antibiotic
      therapy. M. abscessus subsp abscessus has multiple innate antibiotic resistance
      mechanisms, but the most important one described so far is an inducible
      erythromycin methylase (erm) gene. M. abscessus subsp abscessus isolates may
      appear macrolide susceptible on initial in vitro testing but become macrolide
      resistant after exposure to macrolide. It is therefore very important to test
      clinically significant M. abscessus subsp abscessus isolates for erm gene
      activity. Remarkably, controversy still exists about the taxonomy and
      nomenclature of M. abscessus subspecies including subsp abscessus, subsp
      massiliense and subsp bolletii. Identification of these subspecies is not moot as
      M. abscessus subsp massiliense does not have an active erm gene resulting in both
      in vitro and in vivo susceptibility to macrolide. It is imperative from the
      clinician's perspective that mycobacterial laboratories correctly and rapidly
      identify M. abscessus to the subspecies level. Unfortunately, there are no
      reliably or predictably effective treatment regimens for M. abscessus subsp
      abscessus and better, more effective antimicrobial agents are badly needed.
      Surgical resection of involved lung tissue as an adjunct to antibiotic therapy is
      beneficial in selected patients but cannot be broadly applied. Overall, M.
      abscessus subsp abscessus remains a formidable respiratory mycobacterial
      pathogen, one that we are only beginning to understand microbiologically and one
      that as yet consistently evades our best efforts at successful therapeutic
      outcomes. 'trouble ahead, trouble behind, and you know that notion just crossed
      my mind'.Casey Jones, Grateful Dead (1970). 

PMID- 25580263
TI  - S1P signaling: new therapies and opportunities.
AB  - Development of sphingosine-1-phosphate receptor 1 (S1P1) modulators to dampen
      inflammation and its sequelae is becoming increasingly promising for treating
      medical conditions characterized by significant immunopathology. As shown by the
      non-selective S1P receptor modulator FTY720 (fingolimod [Gilenya((r))]) in the
      treatment of relapsing-remitting multiple sclerosis (MS), the ability to use S1P1
      modulation to precisely block immune cell traffic-immunomodulation-while
      maintaining immunosurveillance, has opened therapeutic opportunities in various
      other immune-derived chronic pathologies, including inflammatory bowel disease
      (IBD), lupus, psoriasis, as well as, potentially, in early acute viral
      respiratory infection. Proof-of-concept studies across validated animal models
      with S1P receptor modulators highly selective for S1P1, such as BAF-312
      (Siponimod), KRP-203, ONO-4641 (Ceralifimod), ponesimod and RPC-1063, and
      emerging clinical trials for safety and efficacy in humans, particularly in MS,
      ulcerative colitis (UC) and psoriasis, have set the stage for us to consider
      additional testing in various other autoimmune diseases. 

PMID- 25580262
TI  - Management of colorectal cancer.
AB  - Colorectal cancer is one of the most frequent solid tumors in the Western world.
      Treatment options are dependent on the stage of the disease, the performance
      status of the patient, and increasingly the molecular makeup of the tumor. In
      countries with surveillance programs, the incidence rate as well as the mortality
      rate has gone down because of the earlier stages at which the tumors are
      detected. For rectal cancer, standard of care differs from that of colon cancer
      with regard to perioperative treatment. In the metastatic setting, treatment
      options are uniform for colorectal cancer. Over the years, treatment options have
      emerged from single-agent 5-fluorouracil (5-FU) treatment to combination regimens
      using 5-FU and oxaliplatin or irinotecan or both. Treatment efficacy in the
      metastatic setting has been increased with the introduction of targeted
      substances. These include (a) the anti-vascular endothelial growth factor-A (anti
      VEGF-A) antibody bevacizumab, (b) the anti-epidermal growth factor receptor (anti
      EGFR) antibodies cetuximab and panitumumab, (c) the anti-angiogenic multi-kinase
      inhibitor regorafenib, and (d) the anti-angiogenic compound aflibercept. Anti
      EGFR antibodies have shown efficacy only in the subpopulations of tumors that do
      not have any mutation in KRAS and NRAS exon 2, 3, 4. Physicians have the choice
      in the first line to use anti-EGFR or anti-VEGF inhibitors in combination with
      chemotherapy based on treatment goals and patient performance. In recent years,
      tumor location has been shown to be prognostic and predictive for clinical
      outcome. Right-sided sporadic colon cancers differ significantly in molecular
      characteristics and, with the exception of microsatellite instability (MSI-H)
      tumors, are associated with poor prognosis. Tumors based on hereditary non
      polyposis colorectal cancer, on the other hand, have excellent prognosis in stage
      II and III disease. Recent efforts have focused on the molecular classification
      of colorectal cancer with the purpose of establishing molecularly defined
      subgroups. 

PMID- 25580264
TI  - Mechanisms of left-right asymmetry and patterning: driver, mediator and
      responder.
AB  - The establishment of a left-right (LR) organizer in the form of the ventral node
      is an absolute prerequisite for patterning the tissues on contralateral sides of
      the body of the mouse embryo. The experimental findings to date are consistent
      with a mechanistic paradigm that the laterality information, which is generated
      in the ventral node, elicits asymmetric molecular activity and cellular behaviour
      in the perinodal tissues. This information is then relayed to the cells in the
      lateral plate mesoderm (LPM) when the left-specific signal is processed and
      translated into LR body asymmetry. Here, we reflect on our current knowledge and
      speculate on the following: (a) what are the requisite anatomical and functional
      attributes of an LR organizer, (b) what asymmetric information is emanated from
      this organizer, and (c) how this information is transferred across the paraxial
      tissue compartment and elicits a molecular response specifically in the LPM. 

PMID- 25580265
TI  - Is bipolar always bipolar? Understanding the controversy on bipolar disorder in
      children.
AB  - Dramatically increasing prevalence rates of bipolar disorder in children and
      adolescents in the United States have provoked controversy regarding the
      boundaries of manic symptoms in child and adolescent psychiatry. The serious
      impact of this ongoing debate on the treatment of affected children is reflected
      in the concomitant increase in prescription rates for antipsychotic medication. A
      key question in the debate is whether this increase in bipolar disorder in
      children and adolescents is based on a better detection of early-onset bipolar
      disorder-which can present differently in children and adolescents-or whether it
      is caused by an incorrect assignment of symptoms which overlap with other widely
      known disorders. So far, most findings suggest that the suspected symptoms, in
      particular chronic, non-episodic irritability (a mood symptom presenting with
      easy annoyance, temper tantrums and anger) do not constitute a developmental
      presentation of childhood bipolar disorder. Additional research based on
      prospective, longitudinal studies is needed to further clarify the developmental
      trajectories of bipolar disorder and the diagnostic status of chronic, non
      episodic irritability. 

PMID- 25580267
TI  - Recent advances in contraception.
AB  - Focusing on intrauterine contraceptives (IUC), contraceptive implants, and
      emergency contraceptives, we review recent advances in contraceptive development
      and discuss progress in policies to improve access to the most effective methods.
      We report on the shift in practice towards routinely providing IUCs and implants
      to young and nulliparous women, prompted in part by the reduced diameter of the
      insertion tube for the Mirena IUC and the development of a smaller IUC called
      Skyla. Additionally, we describe the new SCu300A intrauterine ball and the
      development of an implant called Nexplanon, which comes with a preloaded
      inserter. We also discuss the efficacy of ulipristal acetate versus
      levonorgestrel for emergency contraception, especially for women who weigh more
      than 75 kg. Finally, in light of the increasing interest in providing IUCs and
      implants to women in the immediate postpartum and post-abortion periods, we
      consider the rationale for this change in practice and review the progress that
      has been made so far in the United States. 

PMID- 25580266
TI  - Update on hidradenitis suppurativa: connecting the tracts.
AB  - Hidradenitis suppurativa (HS) is a debilitating skin disease characterized by
      recurrent abscesses, sinus tract formation, and scarring. Prevalence estimates
      range from 0.053% to 4.1%, although HS is likely an underdiagnosed disease.
      Although the first reports of HS date back to the mid-19th century, the disease
      continues to plague patients and physicians desperate for a definitive treatment.
      Advances in the understanding of the disease process include the possibility of a
      defective basement membrane at the sebofollicular junction of the
      folliculopilosebaceous unit (FPSU; that is, where the sebaceous gland empties
      into the hair follicle) as an initiating event followed by secondary bacterial
      colonization. New evidence suggests that bacteria living in a community, known as
      a biofilm, rather than single planktonic bacteria in HS lesions may explain why
      HS can be resistant to current antibiotic treatment regimens. Available treatment
      options have expanded to include triple-antibiotic therapy, tumor necrosis factor
      (TNF-alpha) and interleukin-1 (IL-1) inhibitors (biologics), laser therapy, and
      surgical excision, including the skin tissue-sparing excision with
      electrosurgical peeling procedure. Despite the array of treatments available,
      many patients continue to struggle with the embarrassment, pain, odor, and
      frustration that accompany this often isolating disease. Physicians should
      address comorbidities in HS, including the psychosocial issues patients with HS
      frequently encounter. Patients can be directed to HS support groups, where they
      can openly discuss their frustrations, share their experiences in dealing with
      HS, and band together to advocate for themselves. HS is misunderstood by both
      patients and physicians, often resulting in a delay in clinical presentation and
      diagnosis. Patients and physicians across multiple specialties must work together
      to expand awareness of and interest in HS, so that one day, individuals with HS
      can be freed from this crippling disease. 

PMID- 25580268
TI  - Brain metastasis and treatment.
AB  - Despite major therapeutic advances in the management of patients with systemic
      malignancies, management of brain metastases remains a significant challenge.
      These patients often require multidisciplinary care that includes surgical
      resection, radiation therapy, chemotherapy, and targeted therapies. Complex
      decisions about the sequencing of therapies to control extracranial and
      intracranial disease require input from neurosurgeons, radiation oncologists, and
      medical/neuro-oncologists. With advances in understanding of the biology of brain
      metastases, molecularly defined disease subsets and the advent of targeted
      therapy as well as immunotherapeutic agents offer promise. Future care of these
      patients will entail tailoring treatment based on host (performance status and
      age) and tumor (molecular cytogenetic characteristics, number of metastases, and
      extracranial disease status) factors. Considerable work involving preclinical
      models and better clinical trial designs that focus not only on effective control
      of tumor but also on quality of life and neurocognition needs to be done to
      improve the outcome of these patients. 

PMID- 25580269
TI  - Recent advances in mechanical ventilation in patients without acute respiratory
      distress syndrome.
AB  - While being an essential part of general anesthesia for surgery and at times even
      a life-saving intervention in critically ill patients, mechanical ventilation has
      a strong potential to cause harm. Certain ventilation strategies could prevent,
      at least to some extent, the injury caused by this intervention. One essential
      element of so-called 'lung-protective' ventilation is the use of lower tidal
      volumes. It is uncertain whether higher levels of positive end-expiratory
      pressures have lung-protective properties as well. There are indications that too
      high oxygen fractions of inspired air, or too high blood oxygen targets, are
      harmful. Circumstantial evidence further suggests that spontaneous modes of
      ventilation are to be preferred over controlled ventilation to prevent harm to
      respiratory muscle. Finally, the use of restrictive sedation strategies in
      critically ill patients indirectly prevents ventilation-induced injury, as daily
      spontaneous awakening and breathing trials and bolus instead of continuous
      sedation are associated with shorter duration of ventilation and shorten the
      exposure to the injurious effects of ventilation. 

PMID- 25580271
TI  - Recent advances in the treatment of non-small cell and small cell lung cancer.
AB  - Recent presentations at the American Society of Clinical Oncology (ASCO) meeting
      from 30 May to 3 June, 2014, will impact routine clinical care and the
      development of clinical trials in non-small cell lung cancer (NSCLC) and
      extensive stage small cell lung cancer (ES-SCLC). Patients with activating
      epidermal growth factor receptor (EGFR) mutations, defined as exon 19 and exon 21
      L858R point mutations, experience a high objective response rate and prolonged
      progression-free survival with EGFR tyrosine kinase inhibitors. However,
      inevitably, patients experience disease progression and the most common mechanism
      of acquired resistance is an EGFR exon 20 T790M mutation. Several agents
      (AZD9291, CO-1686 and HM61713) have demonstrated impressive activity in patients
      with T790M resistance mutations. Additional data on the efficacy of first-line
      therapy with afatinib and the combination of erlotinib and bevacizumab for
      patients with EGFR mutant NSCLC were presented. The results of a phase III trial
      of crizotinib compared to platinum-pemetrexed in the first-line setting, and a
      phase I trial and expansion cohort of ceritinib, provided additional efficacy and
      toxicity data for patients with anaplastic lymphoma kinase rearranged NSCLC. A
      phase III trial of cisplatin and gemcitabine, with and without necitumumab,
      revealed an improvement in overall survival with the addition of necitumumab in
      patients with squamous NSCLC. In the second-line setting, a phase III trial of
      docetaxel with ramucirumab or placebo revealed an improvement in overall survival
      with the addition of ramucirumab. In extensive stage small cell lung cancer phase
      III trials of consolidative thoracic radiation therapy and prophylactic cranial
      radiation failed to reveal an improvement in overall survival. 

PMID- 25580270
TI  - Management of lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM), a multisystem disease affecting almost
      exclusively women, is characterized by cystic lung destruction and presents with
      dyspnea, recurrent pneumothoraxes, chylous effusions, lymphangioleiomyomas, and
      angiomyolipomas. It is caused by the proliferation of a cancer-like LAM cell that
      possesses a mutation in either the tuberous sclerosis complex (TSC)1 or TSC2
      genes. This article reviews current therapies and new potential treatments that
      are currently undergoing investigation. The major development in the treatment of
      LAM is the discovery of two mammalian target of rapamycin (mTOR) inhibitors,
      sirolimus and everolimus, as effective drugs. However, inhibition of mTOR
      increases autophagy, which may lead to enhanced LAM cell survival. Use of
      autophagy inhibitors, for example, hydroxychloroquine, in combination with
      sirolimus is now the subject of an ongoing drug trial (SAIL trial). Another
      consequence of mTOR inhibition by sirolimus is an increase in Rho activity,
      resulting in reduced programmed cell death. From these data, the concept evolved
      that a combination of sirolimus with disruption of Rho activity with statins
      (e.g. simvastatin) may increase TSC-null cell death and reduce LAM cell survival.
      A combined trial of sirolimus with simvastatin is under investigation (SOS
      trial). Since LAM occurs primarily in women and TSC-null cell survival and tumor
      growth is promoted by estrogens, the inhibition of aromatase to block estrogen
      synthesis is currently undergoing study (TRAIL trial). Other targets, for
      example, estrogen receptors, mitogen-activated protein kinase inhibitors,
      vascular endothelial growth factor-D signaling pathway, and Src kinase, are also
      being studied in experimental model systems. As in the case of cancer,
      combination therapy may become the treatment of choice for LAM. 

PMID- 25580272
TI  - Vitamin D and immunity.
AB  - Vitamin D deficiency has been linked to an increased risk of a wide range of
      adverse health outcomes. The active form of vitamin D has an important role in
      calcium metabolism and in bone mineralisation, but the evidence for other health
      outcomes is mixed, with the strongest effects seen in the weakest epidemiological
      study designs. There are plausible pathways whereby vitamin D deficiency can
      impair immune function, resulting in both overactivity and increased risk of
      autoimmune disease, as well as immune suppression with poorer resistance to
      infection. Vitamin D status may influence the bacterial flora that constitute the
      microbiome and affect immune function through this route. Exposure of the skin to
      ultraviolet radiation causes the production of a range of chemicals, including
      vitamin D, and new research is exploring possible vitamin D-independent
      immunomodulatory pathways. 

PMID- 25580274
TI  - Recent advances in understanding and managing Chlamydia trachomatis infections.
AB  - Worldwide, Chlamydia trachomatis infections rank among the most common sexually
      transmitted infections (STI), and cause notable reproductive morbidity in women.
      Although advances in highly accurate and non-invasive diagnostic testing have
      allowed for better estimation of the burden of disease-especially the
      asymptomatic state-we still lack a true point-of-care test, and many infections
      go undetected and untreated. Moreover, limited resources and effort for managing
      sexual partners of those in whom infection is actually identified comprise a
      major challenge to control. Here, we review the current state of understanding of
      this common infection, and efforts to control it. 

PMID- 25580275
TI  - Commentary: Management of hypospadias.

PMID- 25580273
TI  - Management of hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) is a disease characterized by hemolysis,
      thrombocytopenia, and acute kidney injury, although other organs may be involved.
      Most cases are due to infection with Shiga toxin-producing Escherichia coli
      (STEC). Early identification and initiation of best supportive care, with
      microbiological input to identify the pathogen, result in a favorable outcome in
      most patients. The remaining 10% of HUS cases are classed together as atypical
      HUS and have a diverse etiology. The majority are due to inherited or acquired
      abnormalities that lead to a failure to control complement activation. Atypical
      HUS occurring in other situations (for example, related to pregnancy or kidney
      transplantation) may also involve excessive complement activation. Plasma
      therapies can reverse defective complement control, and it is now possible to
      specifically target complement activation. This has led to improved outcomes in
      patients with atypical forms of HUS. We will review our current understanding of
      the pathogenesis of HUS and how this has led to advances in patient care. 

PMID- 25580276
TI  - Inflammation and Cell Death in Age-Related Macular Degeneration: An
      Immunopathological and Ultrastructural Model.
AB  - The etiology of Age-related Macular Degeneration (AMD) remains elusive despite
      the characterization of many factors contributing to the disease in its late
      stage phenotypes. AMD features an immune system in flux, as shown by changes in
      macrophage polarization with age, expression of cytokines and complement,
      microglial accumulation with age, etc. These point to an allostatic overload,
      possibly due to a breakdown in self vs. non-self when endogenous compounds and
      structures acquire the appearance of non-self over time. The result is
      inflammation and inflammation-mediated cell death. While it is clear that these
      processes ultimately result in degeneration of retinal pigment epithelium and
      photoreceptor, the prevalent type of cell death contributing to the various
      phenotypes is unknown. Both molecular studies as well as ultrastructural
      pathology suggest pyroptosis, and perhaps necroptosis, are the predominant
      mechanisms of cell death at play, with only minimal evidence for apoptosis.
      Herein, we attempt to reconcile those factors identified by experimental AMD
      models and integrate these data with pathology observed under the electron
      microscope-particularly observations of mitochondrial dysfunction, DNA leakage,
      autophagy, and cell death. 

PMID- 25580278
TI  - Measuring Visual Function Using the MultiQuity System: Comparison with an
      Established Device.
AB  - Purpose. To compare measures of visual acuity (VA) and contrast sensitivity (CS)
      from the Thompson Xpert 2000 and MultiQuity (MiQ) devices. Methods. Corrected
      distance VA (CDVA) and CS were measured in the right eye of 73 subjects, on an
      established system (Thompson Xpert) and a novel system (MiQ 720). Regression was
      used to convert MiQ scores into the Thompson scale. Agreement between the
      converted MiQ and Thompson scores was investigated using standard agreement
      indices. Test-retest variability for both devices was also investigated, for a
      separate sample of 24 subjects. Results. For CDVA, agreement was strong between
      the MiQ and Thomson devices (accuracy = 0.993, precision = 0.889, CCC = 0.883).
      For CS, agreement was also strong (accuracy = 0.996, precision = 0.911, CCC =
      0.907). Agreement was unaffected by demographic variables or by presence/absence
      of ocular pathology. Test-retest agreement indices for both devices were
      excellent: in the range 0.88-0.96 for CDVA and in the range 0.90-0.98 for CS.
      Conclusion. MiQ measurements exhibit strong agreement with corresponding Thomson
      measurements, and test-retest results are good for both devices. Agreement
      between the two devices is unaffected by age or ocular pathology. 

PMID- 25580277
TI  - Interstitial Lung Disease Associated with mTOR Inhibitors in Solid Organ
      Transplant Recipients: Results from a Large Phase III Clinical Trial Program of
      Everolimus and Review of the Literature.
AB  - Interstitial lung disease (ILD) has been reported with the use of mammalian
      target of rapamycin inhibitors (mTORi). The clinical and safety databases of
      three Phase III trials of everolimus in de novo kidney (A2309), heart (A2310),
      and liver (H2304) transplant recipients (TxR) were searched using a standardized
      MedDRA query (SMQ) search for ILD followed by a case-by-case medical evaluation.
      A literature search was conducted in MEDLINE and EMBASE. Out of the 1,473 de novo
      TxR receiving everolimus in Phase III trials, everolimus-related ILD was
      confirmed in six cases (one kidney, four heart, and one liver TxR) representing
      an incidence of 0.4%. Everolimus was discontinued in three of the four heart TxR,
      resulting in ILD improvement or resolution. Outcome was fatal in the kidney TxR
      (in whom everolimus therapy was continued) and in the liver TxR despite
      everolimus discontinuation. The literature review identified 57 publications on
      ILD in solid organ TxR receiving everolimus or sirolimus. ILD presented months or
      years after mTORi initiation and symptoms were nonspecific and insidious. The
      event was more frequent in patients with a late switch to mTORi. In most cases,
      ILD was reversed after prompt mTORi discontinuation. ILD induced by mTORi is an
      uncommon and potentially fatal event warranting early recognition and drug
      discontinuation. 

PMID- 25580279
TI  - Factors associated with significant ocular injury in conservatively treated
      orbital fractures.
AB  - Purpose. To determine factors associated with the presence of significant ocular
      injury in subjects with orbital fractures. Subjects. A consecutive prospective
      cohort of 161 patients presenting to a general tertiary referral hospital with
      orbital fractures and undergoing initial conservative treatment was identified.
      Subjects were assessed at time of injury for the need for emergency surgery, and
      those initially treated conservatively were subsequently followed up by the
      Ophthalmology Department to assess for ocular injury requiring ophthalmic
      management at 1-7 days after injury. Associations between ocular injury and age,
      sex, visual acuity, presence of blowout fracture, extent of orbital involvement,
      and presence of distant facial fractures were assessed. Results. 142 male
      (average age of 32 [95% CI 30-35]) and 19 female (average age of 49 [95% CI 39
      59]) subjects were identified. 17 subjects were diagnosed with significant ocular
      injury. Ocular injury was significantly associated with LogMAR VA worse than 0.2
      (OR 49 [95% CI 11-217, P < 0.0001]), but no relationship was noted for age, sex,
      presence of blowout fracture, extent of fractures, or presence of distal facial
      fractures. LogMAR visual acuity worse than or equal to 0.2 had a 98% negative
      predictive value for ocular injury in the setting of orbital fractures.
      Conclusions. Demographic and nonophthalmic fracture characteristics were not
      useful predictors of ocular injury in orbital fractures. LogMAR visual acuity
      worse than or equal to 0.2 is a highly sensitive and useful guide of the need for
      ophthalmic referral in subjects with orbital fractures. 

PMID- 25580280
TI  - Interocular Shift of Visual Attention Enhances Stereopsis and Visual Acuities of
      Anisometropic Amblyopes beyond the Critical Period of Visual Development: A Novel
      Approach.
AB  - Aims. Increasing evidence shows that imbalanced suppressive drive prior to
      binocular combination may be the key factor in amblyopia. We described a novel
      binocular approach, interocular shift of visual attention (ISVA), for treatment
      of amblyopia in adult patients. Methods. Visual stimuli were presented
      anaglyphically on a computer screen. A square target resembling Landolt C had 2
      openings, one in red and one in cyan color. Through blue-red goggles, each eye
      could only see one of the two openings. The patient was required to report the
      location of the opening presented to the amblyopic eye. It started at an opening
      size of 800 sec of arc, went up and down in 160 sec of arc step, and stopped when
      reaching the 5th reversals. Ten patients with anisometropic amblyopia older than
      age 14 (average age: 26.7) were recruited and received ISVA treatment for 6
      weeks, with 2 training sessions per day. Results. Both Titmus stereopsis (z = 
      2.809, P = 0.005) and Random-dot stereopsis (z = -2.317, P = 0.018) were
      significantly improved. Average improvement in best corrected visual acuity
      (BCVA) was 0.74 line (t = 5.842, P < 0.001). Conclusions. The ISVA treatment may
      be effective in treating amblyopia and restoring stereoscopic function. 

PMID- 25580281
TI  - Presence of Dry Eye in Patients with Hashimoto's Thyroiditis.
AB  - Purpose. To evaluate the tear function tests in patients with Hashimoto's
      thyroiditis and to compare the results with healthy subjects. Methods. A hundred
      and ten patients with Hashimoto's thyroiditis and 100 healthy subjects were
      included in this study. The presence of thyroid-associated ophthalmopathy and
      tear function tests were evaluated clinically. The results were first compared
      between the patients and the control groups and then compared between patients
      with NOSPECS and patients without NOSPECS. Logistic regression analyses of the
      risk factors for dry eye including sex, gender, free plasma thyroxine, proptosis,
      upper eyelid margin-reflex distance, and duration of the disease were also
      evaluated. Results. The mean ocular surface disease index score was significantly
      higher and mean Schirmer and mean tear break-up time scores were significantly
      lower in patients compared to control subjects. Mean Schirmer and tear break-up
      time scores were found to be significantly lower in patients with NOSPECS when
      compared to the patients without NOSPECS. Both proptosis and free plasma
      thyroxine levels were significantly associated with dry eye. Conclusions.
      Patients with Hashimoto's thyroiditis tend to develop dry eye more common than
      healthy subjects. Proptosis and lower free plasma thyroxine levels were found to
      be risk factors for the presence of dry eye. 

PMID- 25580282
TI  - The Association between Diabetic Retinopathy and Levels of Ischemia-Modified
      Albumin, Total Thiol, Total Antioxidant Capacity, and Total Oxidative Stress in
      Serum and Aqueous Humor.
AB  - Purpose. To investigate the oxidant and antioxidant status of patients with type
      2 diabetes mellitus and nonproliferative diabetic retinopathy (DRP). Methods.
      Forty-four patients who had cataract surgery were enrolled in the study. We
      included 22 patients with DRP in one group and 22 patients in the control group.
      Samples of aqueous humor and serum were taken from all patients. Serum and
      aqueous ischemia-modified albumin (IMA), total thiol, total antioxidant capacity
      (TAC), and total oxidative stress (TOS) levels were compared in two groups.
      Results. Median serum IMA levels were 44.80 absorbance units in the DRP group and
      40.15 absorbance units in the control group (P = 0.031). Median serum total thiol
      levels in the DRP group were significantly less than those in the control group
      (3051.13 and 3910.12, resp., P = 0.004). Mean TOS levels in the serum were 2.93
      +/- 0.19 in the DRP group and 2.61 +/- 0.26 in the control group (P = 0.039). The
      differences in mean total thiol, TAC, and TOS levels in the aqueous humor and
      mean TAC levels in the serum were not statistically significant. Conclusion. IMA,
      total thiol, and TOS levels in the serum might be useful markers in monitoring
      the risk of DRP development. 

PMID- 25580283
TI  - Determinants of the Morning-Evening Home Blood Pressure Difference in Treated
      Hypertensives: The HIBA-Home Study.
AB  - Background. The morning home blood pressure (BP) rise is a significant
      asymptomatic target organ damage predictor in hypertensives. Our aim was to
      evaluate determinants of home-based morning-evening difference (MEdiff) in
      Argentine patients. Methods. Treated hypertensive patients aged >=18 years
      participated in a cross-sectional study, after performing home morning and
      evening BP measurement. MEdiff was morning minus evening home average results.
      Variables identified as relevant predictors were entered into a multivariable
      linear regression analysis model. Results. Three hundred sixty-seven medicated
      hypertensives were included. Mean age was 66.2 (14.5), BMI 28.1 (4.5), total
      cholesterol 4.89 (1.0) mmol/L, 65.9% women, 11.7% smokers, and 10.6% diabetics.
      Mean MEdiff was 1.1 (12.5) mmHg systolic and 2.3 (6.1) mmHg diastolic,
      respectively. Mean self-recorded BP was 131.5 (14.1) mmHg systolic and 73.8 (7.6)
      mmHg diastolic, respectively. Mean morning and evening home BPs were 133.1 (16.5)
      versus 132 (15.7) systolic and 75.8 (8.4) versus 73.5 (8.2) diastolic,
      respectively. Significant beta-coefficient values were found in systolic MEdiff
      for age and smoking and in diastolic MEdiff for age, smoking, total cholesterol,
      and calcium-channel blockers. Conclusions. In a cohort of Argentine medicated
      patients, older age, smoking, total cholesterol, and use of calcium channel
      blockers were independent determinants of home-based MEdiff. 

PMID- 25580284
TI  - Sociodemographic correlates of modifiable risk factors for hypertension in a
      rural local government area of oyo state South west Nigeria.
AB  - Modifiable risk factors of hypertension contribute significantly to all-cause
      morbidity and mortality worldwide. The study aimed to determine the prevalence of
      and the association of modifiable risk factors with hypertension in rural
      community. A cross-sectional study was conducted among 166 male and 201 female
      adults of 18 years and above using cluster sampling technique. Data were
      collected using modified WHO STEPS instrument and hypertensive subjects were
      defined as those with systolic greater than or equal to 140 and diastolic of 90
      mmHg. Data were analyzed with SPSS version 17 with level of significance at P <
      0.05. The mean age of the subjects was 36.36 (+/-16.88) years and mean systolic
      and diastolic pressures were 124 (+/-16.93) and 76.32 (+/-11.85) mmHg,
      respectively. The prevalence of hypertension was high (22.9%) in this rural
      communities but awareness was low, 10.71%. The prevalence of alcohol consumption,
      sedentary lifestyle, abnormal weight, inadequate sleep, smoking, significant
      stress, and female use of hormonal contraceptives was 149 (40.6%), 91 (24.8%), 88
      (24.0%), 122 (33.2%), 14 (3.8%), 65 (17.7%), and 53 (26.5%), respectively.
      Overweight, sex, inadequate sleep, and stress were established as positive
      predictors of hypertension. The rising prevalence of hypertension and its
      modifiable risk factors in rural communities require prompt interventions
      directed at reversing these trends. 

PMID- 25580285
TI  - The prevalence of antinuclear antibodies in patients with sarcoidosis.
AB  - Introduction. Sarcoidosis, which is a chronic inflammatory granulomatous disease,
      can mimic different rheumatologic diseases including connective tissue diseases.
      Antinuclear antibodies are the markers used for connective tissue diseases. Aim.
      To determine antinuclear antibody frequency and any possible correlation with
      clinical and laboratory data in sarcoidosis patients. Material and Method. Forty
      two sarcoidosis patients, 45 rheumatoid arthritis patients, and 45 healthy
      volunteers who were followed up in rheumatology outpatient clinic were included
      in this study. Demographic, clinical, serological, and radiological data of all
      patients were recorded. Antinuclear antibodies were determined with indirect
      immunofluorescent method and 1/100 titration was accepted as positive. The cases
      that were ANA positive were evaluated with immunoblot method. Results. Average
      age of the 42 patients (10 males) with sarcoidosis was 45.2 (20-70 years), and
      average disease duration was 3.5 years. ANA positivity was detected in 12 (28.5%)
      patients with sarcoidosis (1/100 in 10 patients, 1/320 in two patients), in 19 of
      RA patients (42.2%), and in two of healthy volunteers in low titer (P < 0.001).
      In the subgroup analysis made by immunblot test, one patient had anticentromere
      antibody, one had anti-Ro antibody, one had anti-Scl-70 antibody, one had anti
      dsDNA antibody, and eight patients were negative. The two patients who had
      anticentromere and anti-Scl-70 antibodies had also Sjogren's syndrome and
      scleroderma diagnosis, respectively. Discussion. The prevalence of ANA in
      patients with sarcoidosis was found to be significantly higher than healthy
      control group and lower than RA patients. This result shows that ANA may have an
      important role in the pathogenesis of sarcoidosis and also could be important in
      revealing the overlap syndromes of sarcoidosis-connective tissue diseases.
      Further studies with larger series are necessary in this subject. 

PMID- 25580286
TI  - Intravenous immunoglobulin treatment in chronic neurological diseases: do we have
      maintenance dose right?
AB  - Objectives. We tried to define, on individual basis, minimal effective
      maintenance dose of intravenous immunoglobulins (IVIG) in 26 patients with
      chronic neurological conditions requiring long-term IVIG treatment. Methods.
      Clinical criteria were reviewed in individual cases (Phase 1) followed by
      titration phase (Phase 2, 12 months) and posttitration/follow-up phase (Phase 3,
      3 months). Objective neurological examination and patient self-reports were used
      for clinical follow-up. Results. 69.2% of patients reported condition as stable,
      26.9% as better, and 3.9% as mildly worse. Original mean monthly dose was 1 g/kg;
      over the period of 12 months we reduced dose of IVIG to mean dose 0.67 g/kg
      (range 0.3-2.5 g/kg, P < 0.0001) which meant reduction by 36.4%. We identified 4
      nonresponders and diagnosis in one case was reclassified to degenerative disease.
      In follow-up phase we reduced dose further to 0.60 g/kg. Cumulative monthly dose
      dropped from 2040 g to 1298 g and to 991 g, respectively. Financial expenses were
      reduced significantly (by -36.4% during titration phase and by -51.4% during
      follow-up phase) (comparing with baseline) (P < 0.0001). Conclusion. Individual
      dose titration leads to significant maintenance IVIG dose reduction with
      preserved clinical efficacy. Maintenance dose below 1 g/kg (in our study around
      0.7 g/kg) has acceptable risk/benefit ratio. 

PMID- 25580287
TI  - HBV and HCV Coinfection among HIV/AIDS Patients in the National Hospital of
      Tropical Diseases, Vietnam.
AB  - Aim. To examine prevalence and characterization of HBV and HCV coinfection among
      HIV/AIDS patients. Methods. This cross-sectional, retrospective study analyzed
      724 HIV/AIDS patients in the HIV clinic at the National Hospital of Tropical
      Diseases (NHTD), from 5/2005 to 4/2011. Results. The prevalence of HBV, HCV, and
      HIV coinfection was 50.3% (364/724), of which HbsAg, HCV, and both of HbsAg, and
      HCV positivity were 8.4%, 35.4%, and 6.5%, respectively. The cohort (364
      patients) with HBV, HCV, and HIV coinfection live in the 30 provinces/cities in
      the North and Central area of Vietnam. We found statistically significant
      associations between heightened risk of coinfection with HIV and HCV in the age
      group 30-39 years (P < 0.001), male gender (P < 0.001), never married patients (P
      < 0.001), patients with a history of injection drug use (P < 0.001), and clinical
      stages 2-4 (P < 0.001). Coinfection with HBV/HIV was statistically significant
      associations between heightened risk of marital status (never married) (P <
      0.001) and those who reported transmission through sexual intercourse.
      Conclusion. Coinfection with viral hepatitis is common in HIV patients; further
      study of the impact and evolution of coinfection is necessary to find effective
      treatment algorithms. 

PMID- 25580289
TI  - Propofol infusion syndrome: a retrospective analysis at a level 1 trauma center.
AB  - Objectives. The propofol infusion syndrome (PRIS), a rare, often fatal, condition
      of unknown etiology, is defined by development of lipemic serum, metabolic
      acidosis, rhabdomyolysis, hepatomegaly, cardiac arrhythmias, and acute renal
      failure. Methods. To identify risk factors for and biomarkers of PRIS, a
      retrospective chart review of all possible PRIS cases during a 1-year period was
      conducted at a level 1 trauma hospital in ICU patients over 18 years of age
      receiving continuous propofol infusions for >=3 days. Additional study inclusion
      criteria included vasopressor support and monitoring of serum triglycerides and
      creatinine. Results. Seventy-two patients, 61 males (84.7%) and 11 females
      (15.3%), satisfied study inclusion criteria; and of these, 3 males met the study
      definition for PRIS, with 1 case fatality. PRIS incidence was 4.1% with a case
      fatality rate of 33%. The mean duration of propofol infusion was 6.96 days. A
      positive linear correlation was observed between increasing triglyceride levels
      and infusion duration, but no correlation was observed between increasing
      creatinine levels and infusion duration. Conclusions. Risk factors for PRIS were
      confirmed as high dose infusions over prolonged periods. Increasing triglyceride
      levels may serve as reliable biomarkers of impending PRIS, if confirmed in future
      investigations with larger sample sizes. 

PMID- 25580288
TI  - Severe/Extreme Hypertriglyceridemia and LDL Apheretic Treatment: Review of the
      Literature, Original Findings.
AB  - Hypertriglyceridemia (HTG) is a feature of numerous metabolic disorders including
      dyslipidemias, metabolic syndrome, and diabetes mellitus type 2 and can increase
      the risk of premature coronary artery disease. HTG may also be due to genetic
      factors (called primary HTG) and particularly the severe/extreme HTG (SEHTG),
      which is a usually rare genetic disorder. Even rarer are secondary cases of SEHTG
      caused by autoimmune disease. This review considers the causes of SEHTG, and
      their management including treatment with low density lipoprotein apheresis and
      analyzes the original findings. 

PMID- 25580290
TI  - A Newly Developed Sublingual Tonometric Method for the Evaluation of Tissue
      Perfusion and Its Validation In Vitro and in Healthy Persons In Vivo and the
      Results of the Measurements in COPD Patients.
AB  - Introduction. Since its first publication in the medical literature, an extremely
      large number of references have demonstrated that the tonometric measurement of
      tissue perfusion is a reliable indicator of the actual condition of critically
      ill patients. Later a new method was developed by the introduction of sublingual
      tonometry for the determination of tissue perfusion. In comparison with gastric
      tonometry, the new method was simpler and could even be used in awake patients.
      Unfortunately, at present, because of severe failures of manufacturing, the
      device is withdrawn from commerce. Materials and Methods. In this study, we
      present a new method using a newly developed tool for the PslCO2 measurement in
      sublingual tonometry as well as the data for its validation in vitro and in vivo
      and the results of 25 volunteers and 54 COPD patients belonging to different GOLD
      groups at their hospitalization due to the acute exacerbation of the disease but
      already in a stable condition at the time of the examination. Results and
      Conclusion. The results of the performed examinations showed that the method is
      suitable for monitoring the actual condition of the patients by mucosal perfusion
      tonometry in the sublingual region. 

PMID- 25580291
TI  - Antimullerian hormone changes after laparoscopic ovarian cystectomy for
      endometrioma compared with the nonovarian conditions.
AB  - Laparoscopic ovarian cystectomy is recommended for surgical procedure of
      endometrioma. The negative impact on ovarian reserve following removal had been
      documented. Little evidence had been reported for nonovarian originated effects.
      Objective. To evaluate the impact of laparoscopic ovarian cystectomy for
      endometrioma on ovarian reserve, measured by serum antimullerian hormone (AMH),
      compared to nonovarian pelvic surgery. Materials and Methods. A prospective study
      was conducted. Women who underwent laparoscopic ovarian cystectomy (LOC) and
      laparoscopic nonovarian pelvic surgery (NOS) were recruited and followed up
      through 6 months. Clinical baseline data and AMH were evaluated. Results. 39 and
      38 participants were enrolled in LOC and NOS groups, respectively. Baseline
      characteristics (age, weight, BMI, and height) and preoperative AMH level between
      2 groups were not statistically different. After surgery, AMH of both groups
      decreased since the first week, at 1 month and at 3 months. However, as compared
      to the LOC group at 6 months after operation, the mean AMH of the NOS group had
      regained its value with a highly significant difference. Conclusion. This study
      demonstrated the negative impact of nonovarian or indirect effects of
      laparoscopic surgery to ovarian reserve. The possible mechanisms are necessary
      for more investigations. 

PMID- 25580293
TI  - Mefloquine and Its Enantiomers Are Active against Mycobacterium tuberculosis In
      Vitro and in Macrophages.
AB  - Objective. Tuberculosis is a serious problem of public health. The increase on
      the number of clinical cases of tuberculosis infected with multidrug resistant
      (MDR) M. tuberculosis calls for the development of novel therapy. Design. We
      investigated the effect of mefloquine and two enantiomers, (+)erythro-mefloquine
      and (+)threo-mefloquine against M. tuberculosis strains in the environment
      resembling the aspects of the granuloma environment and in macrophages. Results.
      The results suggest that mefloquine (racemic mixture) and (+)erythro-mefloquine
      have bactericidal activity against M. tuberculosis strains both in acidic, low
      oxygen tension and in macrophages. The activity, however, was impaired under
      increased osmolarity. Conclusion. Identification of the target for mefloquine in
      the pathogen will allow for the development of novel drugs with antituberculosis
      activity. 

PMID- 25580292
TI  - New Thrombotic Events in Ischemic Stroke Patients with Elevated Factor VIII.
AB  - Background. Heightened levels of Factor VIII (FVIII) have been associated with
      both arterial and venous thrombosis. While elevated FVIII is common during acute
      ischemic stroke (AIS), whether elevated FVIII confers an increased risk for
      recurrent thrombotic events (RTEs) following AIS has not been previously
      explored. Methods. Consecutive AIS patients who presented to our center between
      July 2008 and September 2013 and had FVIII measured during admission were
      identified from our stroke registry. Baseline characteristics and the occurrence
      of RTE (recurrent or progressive ischemic stroke, DVT/PE, and MI) were compared
      in patients with and without elevated FVIII levels. Results. Of the 298 patients
      included, 203 (68.1%) had elevated FVIII levels. Patients with elevated FVIII had
      higher rates of any in-hospital RTE (18.7% versus 8.4%, P = 0.0218). This
      association remained after adjustment for baseline stroke severity and etiology
      (OR 1.01, 95% CI 1.00-1.01, P = 0.0013). Rates of major disability were also
      higher in patients who experienced a RTE (17.8% versus 3.2%, P < 0.0001).
      Conclusion. A significantly higher frequency of in-hospital RTEs occurred in AIS
      patients with elevated FVIII. The occurrence of such events was associated with
      higher morbidity. Further study is indicated to evaluate whether FVIII is a
      candidate biomarker for increased risk of RTEs following AIS. 

PMID- 25580294
TI  - A comparative study on visual choice reaction time for different colors in
      females.
AB  - Reaction time is one of the important methods to study a person's central
      information processing speed and coordinated peripheral movement response. Visual
      choice reaction time is a type of reaction time and is very important for
      drivers, pilots, security guards, and so forth. Previous studies were mainly on
      simple reaction time and there are very few studies on visual choice reaction
      time. The aim of our study was to compare the visual choice reaction time for
      red, green, and yellow colors of 60 healthy undergraduate female volunteers.
      After giving adequate practice, visual choice reaction time was recorded for red,
      green, and yellow colors using reaction time machine (RTM 608, Medicaid,
      Chandigarh). Repeated measures of ANOVA and Bonferroni multiple comparison were
      used for analysis and P < 0.05 was considered statistically significant. The
      results showed that both red and green had significantly less choice visual
      choice reaction (P values <0.0001 and 0.0002) when compared with yellow. This
      could be because individual color mental processing time for yellow color is more
      than red and green. 

PMID- 25580295
TI  - How sex of children with autism spectrum disorders and access to treatment
      services relates to parental stress.
AB  - Parents of children with autism spectrum disorders (ASD) experience higher levels
      of stress in comparison to parents of neurotypical children and consequently are
      more susceptible to negative health and social outcomes (Dunn et al., 2001).
      However, less is known about how individual child characteristics impact stress
      levels in parents of children with ASD. In this study, we examined the
      relationship between individual characteristics (i.e., sex) of children with ASD
      and parental stress. Access to comprehensive treatment services was also examined
      as a contributing factor to parental stress. Parenting stress was higher for
      parents of girls than for parents of boys, and for parents of girls (but not
      boys) fewer services predicted higher parental distress. Findings highlight the
      importance of providing parents of girls with ASD with more tailored support. 

PMID- 25580296
TI  - Variability in the branching pattern of the internal iliac artery in Indian
      population and its clinical importance.
AB  - Internal iliac artery (IIA) is one of the terminal branches of the common iliac
      artery and is the prime artery of pelvis. The artery has many parietal and
      visceral branches and hence the variations are frequently noted. The larger
      branches, namely, the inferior gluteal artery, the superior gluteal artery, and
      the internal pudendal artery, show sufficient regularity in their patterns of
      origin to allow typing. The variability of the IIA and its branching pattern were
      studied by dissecting sixty-eight male pelvic halves (34 right and 34 left) and
      forty-eight female pelvic halves (24 right and 24 left sides). In significant
      number of specimens, IIA terminated without dividing into 2 trunks as against the
      usual description. There was also considerable interchange of branches between
      the 2 terminal divisions. The patterns of branching noted were grouped as per
      Adachi's classification. The incidence was noted to be as follows: type Ia in
      60.6%, type Ib in 2.6%, type IIa in 15.8%, and type III in 21%. The other types
      were not observed in this study. Conclusion. Interventions in the pelvic region
      must take into account the variability of the IIA and its branches that can
      modify the expected relations and may lead to undesired hemorrhagic or embolic
      accidents. 

PMID- 25580297
TI  - Clostridium difficile with Moxifloxacin/Clindamycin Resistance in Vegetables in
      Ohio, USA, and Prevalence Meta-Analysis.
AB  - We (i) determined the prevalence of Clostridium difficile and their antimicrobial
      resistance to six antimicrobial classes, in a variety of fresh vegetables sold in
      retail in Ohio, USA, and (ii) conducted cumulative meta-analysis of reported
      prevalence in vegetables since the 1990s. Six antimicrobial classes were tested
      for their relevance as risk factors for C. difficile infections (CDIs)
      (clindamycin, moxifloxacin) or their clinical priority as exhaustive therapeutic
      options (metronidazole, vancomycin, linezolid, and tigecycline). By using an
      enrichment protocol we isolated C. difficile from three of 125 vegetable products
      (2.4%). All isolates were toxigenic, and originated from 4.6% of 65 vegetables
      cultivated above the ground (n = 3; outer leaves of iceberg lettuce, green
      pepper, and eggplant). Root vegetables yielded no C. difficile. The C. difficile
      isolates belonged to two PCR ribotypes, one with an unusual antimicrobial
      resistance for moxifloxacin and clindamycin (lettuce and pepper; 027-like,
      A(+)B(+)CDT(+); tcdC 18 bp deletion); the other PCR ribotype (eggplant, A(+)B(+)
      CDT(-); classic tcdC) was susceptible to all antimicrobials. Results of the
      cumulative weighted meta-analysis (6 studies) indicate that the prevalence of C.
      difficile in vegetables is 2.1% and homogeneous (P < 0.001) since the first
      report in 1996 (2.4%). The present study is the first report of the isolation of
      C. difficile from retail vegetables in the USA. Of public health relevance,
      antimicrobial resistance to moxifloxacin/clindamycin (a bacterial-associated risk
      factor for severe CDIs) was identified on the surface of vegetables that are
      consumed raw. 

PMID- 25580298
TI  - Robotic Prostatectomy Has a Superior Outcome in Larger Prostates and PSA Density
      Is a Strong Predictor of Biochemical Recurrence.
AB  - Objectives. The aims of this study were to compare the outcomes of robotic
      assisted laparoscopic prostatectomy (RALP) between patients who had larger (>=75
      g) and smaller (<75 g) prostates and to evaluate the performance of PSA density
      (PSAD) in determining the oncological outcome of surgery. Methods and Materials.
      344 patients who underwent RALP at a single institution were included in the
      study. Preoperative risk factors and postoperative, oncological outcomes,
      erectile function, and continence status were recorded prospectively. Results.
      During a mean follow-up of 20 months, biochemical recurrence (PSA > 0.2) was
      observed in 15 patients (4.3%). Prostate size >=75 g was associated with lower
      Gleason score on final pathology (P = 0.004) and lower pathological stage (P =
      0.02) but an increased length of hospital stay (P = 0.05). PSAD on binary
      logistic regression independently predicted biochemical recurrence (BCR) when
      defined as postoperative PSA >0.1 (P = 0.001) and PSA >0.2 (P = 0.039). In both
      instances PSA was no longer a significant independent predictor. Conclusions.
      RALP in large prostates (>=75 g, <150 g) is as safe as RALP in smaller prostates
      and is associated with a lower pathological grade and stage. Higher PSAD is
      independently associated with BCR and is superior to PSA as a predictor of BCR
      after RALP. 

PMID- 25580299
TI  - Assessing the Effect of Composting Cassava Peel Based Substrates on the Yield,
      Nutritional Quality, and Physical Characteristics of Pleurotus ostreatus (Jacq.
      ex Fr.) Kummer.
AB  - Cassava peel based substrate formulations as an alternative substrate were used
      to grow mushrooms. The effect of two compost heights, three composting periods on
      the mycelia growth, physical characteristics, yield, and nutritional qualities of
      Pleurotus ostreatus (Jacq. ex Fr.) Kummer was studied. Mean mycelia growth of
      16.2 cm after a period of seven (7) weeks was the best for 1.5 m compost height.
      Cap diameter and stipe length differed significantly (P < 0.05) with the compost
      heights (0.8 m and 1.5 m). The yield on compost height of 1.5 m, composted for 5
      days, differed significantly (P < 0.05) from that of 0.8 m and gave increasing
      yields as follows: cassava peels and manure, cassava peels only, cassava peels
      and corn cobs (1 : 1 ratio), and cassava peels and corn cobs (1 : 1 ratio) with
      chicken manure. Composting periods (3 and 7 days) gave varying yields depending
      on the compost height. Based on the findings an interaction of 1.5 m compost
      height and 5 days composting period on cassava peels and corncobs (1 : 1 ratio)
      with chicken manure produced the best results. The nutritional quality of the
      mushrooms also differed significantly (P < 0.05), indicating that cassava peels
      could be used as a possible substrate in cultivation of mushroom. 

PMID- 25580300
TI  - Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal
      Liver-Specific Target Genes.
AB  - Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are
      at high risk of severe complications such as hepatocellular carcinoma and
      cirrhosis. Liver damage is caused by the host immune response to infected
      hepatocytes, and we hypothesise that specific microRNAs play a role in this
      complex interaction between virus and host. The study aimed to identify microRNAs
      with aberrant plasma expressions in HBeAg-positive children and with liver
      specific target genes. Methods. By revisiting our previous screen of microRNA
      plasma levels in HBeAg-positive and HBeAg-negative children with chronic
      hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant
      plasma expressions in HBeAg-positive children were identified. MicroRNAs
      targeting liver-specific genes were selected based on bioinformatics analysis and
      validated by qRT-PCR using plasma samples from 34 HBeAg-positive, 26 HBeAg
      negative, and 60 healthy control children. Results. Thirteen microRNAs showed
      aberrant plasma expressions in HBeAg-positive children and targeted liver
      specific genes. In particular, three microRNAs were upregulated and one was
      downregulated in HBeAg-positive children compared to HBeAg-negative and healthy
      control children, which showed equal levels. Conclusion. The identified microRNAs
      might impact the progression of CHB in children. Functional studies are
      warranted, however, to elucidate the microRNAs' role in the immunopathogenesis of
      childhood CHB. 

PMID- 25580301
TI  - E. coli Induced Experimental Model of Primary Biliary Cirrhosis: At Last.
AB  - Recurrent urinary tract infections (UTI) have been considered potential triggers
      of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease
      characterised by progressive destruction of intrahepatic bile ducts. Additional
      support for the link made between PBC and UTI was based on early observations of
      recurrent episodes of bacteriuria in female patients with PBC. A series of large
      epidemiological studies demonstrated a strong correlation between recurrent UTI
      and PBC, initiating a series of studies investigating the role of Escherichia
      coli (E. coli, the most prevalent organism isolated in women with UTI) as a
      trigger of PBC. Immunological evidence of B- and T-cell cross-reactive responses
      implicating PBC-specific autoantigens and E. coli mimics have been clearly
      demonstrated, adding support to the notion that E. coli is a potential infectious
      inducer of PBC in susceptible individuals. One of the major limitations in
      proving the E. coli/PBC association was the lack of reliable E. coli-infected
      animal models of PBC. This review provides an overview of the evidence linking
      this infectious agent with PBC and discusses the pros and cons of a recently
      developed E. coli-infected animal model of PBC. 

PMID- 25580302
TI  - Management of late onset perthes: evaluation of distraction by external fixator-5
      year follow-up.
AB  - Background. Hip distraction in Perthes' disease unloads the joint, which negates
      the harmful effect of the stresses on the articular surfaces, which may promote
      the sound healing of the area of necrosis. We have examined the effect of
      arthrodiastasis on the preservation of the femoral head in older children with
      Perthes' disease. Methods and Materials. Twelve children with age more than 8
      years with Perthes' disease of less than one year were treated with hip
      distraction by a hinged monolateral external fixator. Observation and Results.
      Mean duration of distraction was 13.9 days. These children were evaluated by
      clinicoradiological parameters for a mean period of 32.4 months. There was a
      significant improvement in the range of movements and mean epiphyseal index, but
      the change in the percentage of uncovered head femur was insignificant. There was
      significant improvement in Harris Hip score. Conclusions. Hip distraction by
      hinged monolateral external fixator seems to be a valid treatment option in cases
      with Perthes' disease in the selected group of patients, where poor results are
      expected from conventional treatment. 

PMID- 25580303
TI  - Outcomes of Geriatric Hip Fractures Treated with AFFIXUS Hip Fracture Nail.
AB  - Geriatric hip fractures are one of the commonest fractures worldwide. The purpose
      of this study was to report the outcomes of a series of unstable geriatric hip
      fractures treated with AFFIXUS hip fracture nail. A retrospective study of 100
      unstable geriatric hip fractures treated with AFFIXUS hip fracture nail is
      presented. The mean follow-up duration was 8 months (range 3-32). Of the patients
      83% were female. The average age was 85 years. The fracture was treated by closed
      reduction and intramedullary fixation. The mean acute hospital stay was 17.6
      days. Systemic complications occurred in 29 patients (29%) and local
      complications in 3 patients (3%) including lag screw cutout in one patient (1%),
      lag screw backout in one patient (1%), and deep infection in one patient (1%).
      Mechanical failures and periprosthetic fractures were not observed in our series.
      Fractures united in all patients. Preinjury activity level was recovered in 78%
      of the patients. The results of AFFIXUS hip fracture nail were satisfactory in
      most elderly patients. The unique design of the lag screw and its thread spacing
      had effectively reduced cut-out rate. 

PMID- 25580304
TI  - Cartilage degeneration at symptomatic persistent olecranon physis in adolescent
      baseball players.
AB  - Background. Elbow overuse injuries are common in adolescent baseball players, but
      symptomatic persistent olecranon physis is rare, and its pathogenesis remains
      unclear. Purpose. To examine the histopathological and imaging findings of
      advanced persistent olecranon physis. Methods. The olecranon physes of 2 baseball
      pitchers, aged 14 and 15 years, were examined by preoperative magnetic resonance
      imaging (MRI), and surgical specimens were examined histologically. Results. T2
      weighted MRI revealed alterations in the intrachondral signal intensity possibly
      related to collagen degeneration and increased free water content. Histological
      findings of specimens stained with hematoxylin-eosin showed complete
      disorganization of the cartilage structure, hypocellularity, chondrocyte cluster
      formation, and moderately reduced staining. All these findings are hallmarks of
      osteoarthritis and are suggestive of cartilage degeneration. Conclusion. Growth
      plate degeneration was evident in advanced cases of symptomatic persistent
      olecranon physis. These findings contribute to understanding the pathogenesis of
      this disease. 

PMID- 25580305
TI  - The 2007 los angeles mommy and baby study: a multilevel, population-based study
      of maternal and infant health in los angeles county.
AB  - Objectives. In order to comprehensively examine the risks and resources
      associated with racial-ethnic disparities in adverse obstetric outcomes, the Los
      Angeles County Department of Public Health and the University of California, Los
      Angeles, joined efforts to design and implement the 2007 Los Angeles Mommy and
      Baby (LAMB) study. This paper aims to present the conceptual frameworks
      underlying the study's development, highlight the successful collaboration
      between a research institution and local health department, describe the
      distinguishing characteristics of its methodology, and discuss the study's
      implications for research, programs, and policies. Methods. The LAMB study
      utilized a multilevel, multistage cluster design with a mixed-mode methodology
      for data collection. Two samples were ultimately produced: the multilevel sample
      (n = 4,518) and the augmented final sample (n = 6,264). Results. The LAMB study
      allowed us to collect multilevel data on the risks and resources associated with
      racial-ethnic disparities in adverse obstetric outcomes. Both samples were more
      likely to be Hispanic, aged 20-34 years, completed at least 12 years of
      schooling, and spoke English. Conclusions. The LAMB study represents the
      successful collaboration between an academic institution and local health
      department and is a theoretically based research database and surveillance system
      that informs effective programmatic and policy interventions to improve outcomes
      among LAC's varied demographic groups. 

PMID- 25580306
TI  - Environmental control of adult neurogenesis: from hippocampal homeostasis to
      behavior and disease.

PMID- 25580307
TI  - Mini-implants: new possibilities in interdisciplinary treatment approaches.
AB  - The introduction of mini-implants has broadened the range of tooth movements
      possible by fixed appliance therapy alone. The limits of fixed orthodontic
      treatment have become more a matter of facial appearance than anchorage. Many
      complex cases which would previously have required surgery or functional
      appliances can now be treated with fixed appliance therapy using mini-implants. A
      mutilated dentition case where mini-implants were used to provide anchorage for
      intrusion of molars and retraction of anterior teeth is reported here to
      illustrate this point. 

PMID- 25580308
TI  - Numb chin syndrome as first symptom of diffuse large B-cell lymphoma.
AB  - Numb chin syndrome is a rare sensory neuropathy of the mental nerve characterized
      by numbness, hypoesthesia, paraesthesia, and very rarely pain. Dental causes,
      especially iatrogenic ones, maxillofacial trauma, or malignant neoplasm are
      etiologic factors for this rare syndrome. Many malignant and metastatic neoplasms
      are causing this syndrome, like primary osteosarcoma, squamous cell carcinoma,
      and mandibular metastasis of primary carcinoma of breast, lung, thyroid, kidney,
      prostate, and nasopharynx. Haematological malignancies like acute lymphocytic
      leukaemia, Hodgkin and non-Hodgkin lymphoma, and myeloma can cause this
      neuropathy. The authors report a case of a 71-year-old woman in which the numb
      chin syndrome was the first symptom of the diffuse large B-cell lymphoma, which
      caused infiltration and reabsorption of the alveolar ridge and lower mandibular
      cortex. A biopsy of the mass was performed on fragments of tissue collected from
      the mandibular periosteum, medullary and cortical mandibular bone, and inferior
      alveolar nerve. 

PMID- 25580309
TI  - Treatment of odontogenic myxoma: a multidisciplinary approach-6-year follow-up
      case.
AB  - The most aggressive diseases that affect the oral environment are considered
      tumors of the jaw. The surgical treatment is preferably done by surgical
      resection of the lesion, resulting in a great loss of tissue and esthetics.
      Multidisciplinary planning is required for the rehabilitation of these cases.
      Autogenous grafting techniques or vascularized flaps allow ridge reconstruction
      for implant placement, restoring function, and esthetics. This paper reports a 6
      year follow-up case of an odontogenic myxoma treated with wide resection and
      mandibular bone reconstruction for posterior rehabilitation with dental implants.

PMID- 25580310
TI  - A case of apparent contact dermatitis caused by Toxocara infection.
AB  - Infection from Toxocara species may give rise to a large array of clinical
      symptoms, including apparent manifestations of allergy such as asthma,
      urticaria/angioedema, and dermatitis. We report a case, thus far not described,
      of contact dermatitis attributed to nickel allergy but caused by Toxocara
      infection. The patient was a 53-year-old woman presenting from 10 years a
      dermatitis affecting head, neck, and thorax. Patch tests initially performed gave
      a positive result to nickel, but avoidance of contact with nickel did not result
      in recovery. The patient referred to our Allergy Service in 2010 because of
      dermatitis to feet. Patch testing confirmed the positive result for nickel, but
      expanding the investigation a positive result for IgG antibodies to Toxocara was
      detected by Western blotting and ELISA. Treatment with mebendazole achieved
      immediate efficacy on feet dermatitis. Then, two courses of treatment with
      albendazole resulted in complete regression of dermatitis accompanied by
      development of negative ELISA and Western blotting for Toxocara antibodies. This
      report adds another misleading presentation of Toxocara infection as apparent
      contact dermatitis caused by nickel and suggests bearing in mind, in cases of
      contact dermatitis not responding to avoidance of the responsible hapten and to
      medical treatment, the possible causative role of Toxocara. 

PMID- 25580311
TI  - New onset refractory status epilepticus as an unusual presentation of a suspected
      organophosphate poisoning.
AB  - New onset refractory status epilepticus (NORSE) is a new entity in medical
      literature. It has different infectious and noninfectious etiologies showing a
      devastating impact onto the clinical outcome of patients. Therapy with
      anaesthetic and antiepileptic agents often fails to improve the condition, unless
      the primary cause is rectified. Here is presented the case of a young female with
      a history of depression who after a recent bereavement came to the Emergency
      Department of Aga Khan University Hospital with complaints of drowsiness that
      lasted for few hours. Though she had no history of organophosphate poisoning, her
      physical examination and further investigations were suggestive of the diagnosis.
      During her hospital stay, she developed refractory status epilepticus. Her
      seizures did not respond to standard antiepileptic and intravenous anesthetic
      agents and subsided only after intravenous infusion of atropine for a few days.
      Organophosphate poisoning is a very common presentation in the developing world
      and the associated status epilepticus poses a devastating problem for emergency
      physicians. In patients with suspected organophosphate poisoning with favoring
      clinical exam findings, the continuation of atropine intravenous infusion can be
      a safe option to abate seizures. 

PMID- 25580312
TI  - An interesting cause of hyperandrogenemic hirsutism.
AB  - Mild clinical signs of hyperandrogenism such as hirsutism may appear during the
      menopausal transition as part of the normal aging process, but the development of
      frank virilization suggests a specific source of androgen excess. We report a
      case of a 68-year-old woman with signs of virilization that had started 6 months
      before. Clinical analyses revealed high levels of serum testosterone for a
      postmenopausal woman. Pelvic MRI and abdomen CT showed no evidence of ovarian and
      adrenal tumor. Postmenopausal hyperandrogenism can be the result of numerous
      etiologies ranging from normal physiologic changes to ovarian or rarely adrenal
      tumors. Our patient was found to have iatrogenic hyperandrogenism. This condition
      is rarely reported cause of virilization. 

PMID- 25580313
TI  - Does Gastrointestinal Dysmotility Predispose to Recurrent or Severe Forms of
      Clostridium difficile Infections?
AB  - Clostridium difficile infection (CDI) is the most common cause of hospital
      acquired diarrhea. A limited number of studies have looked at the risk factors
      for recurrent CDI. Mitochondrial NeuroGastroIntestinal Encephalopathy (MNGIE) is
      a rare multisystemic disorder that causes gastrointestinal dysmotility. Herein we
      present a patient with MNGIE who suffered recurrent and severe C. difficile
      infection despite appropriate treatment. We aim to bring the gastroenterologist's
      attention to gastrointestinal dysmotility as a possible risk factor for the
      development of recurrent or severe forms of C. difficile infections. 

PMID- 25580314
TI  - Polyangiitis with granulomatosis as a paraneoplastic syndrome of B-cell lymphoma
      of the lacrimal gland.
AB  - Introduction. The clinical course of an autoimmune paraneoplastic syndrome
      parallels the natural history of the primary malignancy. In most cases, such
      paraneoplastic are syndromes hardly distinguishable from idiopathic autoimmune
      diseases. A case of polyangiitis with granulomatosis as a paraneoplastic syndrome
      in a patient with B-cell Lymphoma of the lacrimal gland has not yet been
      reported. Case Presentation. We present the case of a male patient with a B-cell
      Lymphoma of the lacrimal gland, who debuted with symptoms similar to rheumatoid
      arthritis and acute renal failure, secondary to polyangiitis with granulomatosis.
      The current pathophysiological hypotheses explaining the relationship between a
      lymphoproliferative disease and an autoimmune paraneoplastic disorder are
      discussed. Conclusion. Tumor-associated segmental necrotizing glomerulopathy is a
      very rare manifestation of glomerular diseases. Some atypical clinical features
      should increase the suspicion of an underlying tumor, in which case it is
      essential to treat the primary neoplasia, in order to control the autoimmune
      manifestations. 

PMID- 25580315
TI  - Skin Recurrence of Transformed Mycosis Fungoides Postumbilical Cord Blood
      Transplant despite Complete Donor Chimerism.
AB  - Background. Allogeneic stem cell transplant is the treatment of choice for
      systemic cutaneous T-cell lymphoma (CTCL) which provides graft-versus-lymphoma
      effect. Herein we discuss a case of recurrence of CTCL skin lesions after cord
      blood transplant in a patient who continued to have 100% donor chimerism in bone
      marrow. Case Presentation. A 48-year-old female with history of mycosis fungoides
      (MF) presented with biopsy proven large cell transformation of MF. PET scan
      revealed multiple adenopathy in abdomen and chest suspicious for lymphoma and
      skin biopsy showed large cell transformation. She was treated with multiple
      cycles of chemotherapy. Posttherapy PET scan showed resolution of
      lymphadenopathy. Later she underwent ablative preparative regimen followed by
      single cord blood transplant. Bone marrow chimerism studies at day +60 after
      transplant showed 100% donor cells without presence of lymphoma. However 5 months
      after transplant she had recurrence of MF with the same genotype as prior skin
      lesion. Bone marrow chimerism study continued to show 100% donor cells.
      Conclusion. A differential graft-versus-lymphoma effect in our case prevented
      lymphoma recurrence systemically but failed to do so in skin. We hypothesize that
      this response may be due to presence of other factors in the bone marrow and
      lymph node microenvironments preventing recurrence in these sites. 

PMID- 25580316
TI  - Safe and Successful Yttrium-90 Resin Microsphere Radioembolization in a Heavily
      Pretreated Patient with Chemorefractory Colorectal Liver Metastases after Biliary
      Stent Placement above the Papilla.
AB  - We report a case of safe and successful yttrium-90 resin microsphere
      radioembolization in a patient with a long history of multiple recurrent colon
      cancer hepatic metastases progressing after hepatic resections, hepatic arterial
      chemotherapy, and multiple regimens of systemic chemotherapy. One month prior to
      radioembolization, a biliary stent was placed above the level of the ampulla to
      relieve tumor-related biliary obstruction and normalize bilirubin levels. 

PMID- 25580317
TI  - Lepra reaction with lucio phenomenon mimicking cutaneous vasculitis.
AB  - Leprosy is a disease typically found in the tropics. Patients with leprosy can
      have varying presentation with constitutional symptoms, joint pains, skin
      nodules, and rarely a vasculitis-like picture with skin ulcers and neuropathy. We
      present a young lady who presented with the rare manifestation of skin infarcts
      mimicking cutaneous vasculitis, diagnosed on histopathology to have Lucio
      phenomenon on a background of lepromatous leprosy. With increasing migration and
      widespread use of biologic response modifiers, clinicians all over the world need
      to be aware of various presentations of leprosy as well as needing to keep an
      open mind while considering the differential diagnoses of vasculitis. 

PMID- 25580318
TI  - Fever of unknown origin in a patient with confirmed west nile virus
      meningoencephalitis.
AB  - West Nile Virus (WNV), an RNA arbovirus and member of the Japanese encephalitis
      virus antigenic complex, causes a wide range of clinical symptoms, from
      asymptomatic to encephalitis and meningitis. Nearly all human infections of WNV
      are due to mosquito bites with birds being the primary amplifying hosts. Advanced
      age is the most important risk factor for neurological disease leading most often
      to poor prognosis in those afflicted. We report a case of WNV meningoencephalitis
      in a 93-year-old Caucasian male who presented with fever of unknown origin (FUO)
      and nuchal rigidity that rapidly decompensated within 24 h to a persistent
      altered mental state during inpatient stay. The patient's ELISA antibody titers
      confirmed pathogenesis of disease by WNV; he given supportive measures and
      advanced to an excellent recovery. In regard to the approach of FUO, it is
      important to remain impartial yet insightful to all elements when determining
      pathogenesis in atypical presentation. 

PMID- 25580319
TI  - The first evidence of lyme neuroborreliosis in southern bosnia and herzegovina.
AB  - Lyme borreliosis (LB) is caused by the spirochete Borrelia burgdorferi, which is
      transmitted to humans by ticks of the Ixodes ricinus complex. It is manifested by
      a variety of clinical symptoms and affects skin, joints, heart, and nervous
      system. Neurological manifestations are predictable and usually include
      meningoencephalitis, facial palsy, or radiculopathy. Recently, a dramatic rise in
      the number of diagnosed cases of LB has been observed on the global level. Here
      we show the first case of Lyme neuroborreliosis in southern Bosnia and
      Herzegovina, which was first presented by erythema chronicum migrans.
      Unfortunately, it was not recognized or well treated at the primary care
      medicine. After eight weeks, the patient experienced headache, right facial
      palsy, and lumbar radiculopathy. After the clinical examination, the neurologist
      suspected meningoencephalitis and the patient was directed to the Clinic for
      Infectious Disease of the University Hospital Mostar, where he was admitted. The
      successful antimicrobial treatment with the 21-day course of ceftriaxone was
      followed by normalization of neurological status, and then he was discharged from
      the hospital. This case report represents an alert to all physicians to be aware
      that LB is present in all parts of Bosnia and Herzegovina, as well as in the
      neighboring regions. 

PMID- 25580320
TI  - Epidermoid causing ischemic stroke in the brainstem.
AB  - Intracranial tumors may rarely cause stroke. We report an epidermoid cyst causing
      stroke in a pediatric patient. We have also reviewed the literature and
      pathogenesis of stroke caused by intracranial tumors. 

PMID- 25580321
TI  - Bilateral tubal gestation associated with schistosomiasis in an african woman.
AB  - Background. The incidence of tubal ectopic gestation caused by schistosomiasis
      induced tubal pathology is undocumented in this environment, which may be due to
      rarity of this pathology. Bilateral tubal gestation is common in patients that
      have undergone in vitro fertilization. We report a hitherto undocumented case of
      spontaneous bilateral ectopic gestation following tubal schistosomiasis. Case
      Report. Mrs. OB was a 32-year-old G4P3(+0) (3 alive) woman who complained of
      abdominal pain and bleeding per vaginam of 4 and 2 days' duration respectively
      following 8 weeks of amenorrhea. A clinical impression of ruptured ectopic
      gestation was confirmed by ultrasound scanning. She had bilateral salpingectomy
      with histology of specimens showing bilateral ectopic gestation with Schistosoma
      haematobium induced salpingitis (findings of Schistosoma haematobium ova noted on
      slide). Conclusion. Schistosoma induced salpingitis is a rare but possible cause
      of bilateral tubal gestation. 

PMID- 25580322
TI  - Fetal circulatory variation in an acute incident causing bradycardia.
AB  - Umbilical artery?vein, middle cerebral artery, and ductus venosus Doppler
      velocimetry were performed at 33 weeks of gestation in the settings of an
      intrauterine growth restricted fetus during a heart rate deceleration.
      Interestingly, we recorded a sudden onset redistribution of fetal blood flow with
      fetal bradycardia. Spontaneous normalization of waveforms was observed once fetal
      heart rate returned to normal. Our case provides evidence to circulatory
      variation of a human fetus resulting from an acute incident causing bradycardia. 

PMID- 25580323
TI  - Postoperative radiation therapy for parotid mucoepidermoid carcinoma.
AB  - Salivary gland cancers are rare and represent approximately 5% of all head and
      neck cancers and only 0.3% of all malignancies. The majority (75%) of salivary
      gland tumors occur in the parotid gland, and while benign lesions are more
      common, mucoepidermoid carcinoma (MEC) makes up 40-50% of malignant parotid gland
      tumors. No randomized controlled trials exist regarding the role of adjuvant
      radiation for patients who undergo surgical resection of low-grade MECs. Herein,
      we report two cases of successful postoperative radiation therapy in low-grade,
      pT2N0 MEC of the parotid gland. The role of adjuvant radiation therapy for
      patients with MEC of the parotid gland is based on data from institution reviews
      and lacks data from randomized controlled trials. Per our review of the
      literature, the pathological findings of positive surgical margins and/or
      perineural invasion in two patients with low-grade MEC of the parotid gland
      warranted adjuvant radiation for improved local control after partial
      parotidectomy. Both patients tolerated postoperative radiation therapy with only
      mild side effects and, at last follow-up, five years after completion of therapy,
      had no clinical or radiographic evidence of either local recurrence or distant
      metastasis. 

PMID- 25580324
TI  - Metastasis of laryngeal squamous cell carcinoma to bilateral thigh muscles.
AB  - Importance. Laryngeal cancer infrequently results in distant metastases, but
      metastasis to skeletal muscle is extremely uncommon. Observations. A 55-year-old
      male presenting with progressive dyspnea and hoarseness was found to have Stage
      IVA T4aN2cM0 laryngeal cancer and eventually underwent total laryngectomy. Before
      the patient could be started on adjuvant chemoradiation, the patient developed
      masses on both thighs. Biopsy revealed metastatic squamous cell carcinoma
      consistent with the primary laryngeal cancer. He was offered palliative
      chemotherapy; however, he developed new soft tissue masses to the left of his
      stoma and in the prevertebral area one week later. He also had new cervical and
      supraclavicular nodes and a pathological compression fracture of L3. Patient died
      within 4 months of diagnosis. Conclusions. Distant metastasis such as skeletal
      metastasis portends a poor prognosis. Further studies are required to determine
      the best course of treatment in these patients. 

PMID- 25580325
TI  - Familial Lymphoproliferative Malignancies and Tandem Duplication of NF1 Gene.
AB  - Background. Neurofibromatosis type 1 is a genetic disorder caused by loss-of
      function mutations in a tumor suppressor gene (NF1) which codifies the protein
      neurofibromin. The frequent genetic alterations that modify neurofibromin
      function are deletions and insertions. Duplications are rare and phenotype in
      patients bearing duplication of NF1 gene is thought to be restricted to
      developmental abnormalities, with no reference to cancer susceptibility in these
      patients. We evaluated a patient who presented with few clinical signs of
      neurofibromatosis type 1 and a conspicuous personal and familiar history of
      different types of cancer, especially lymphoproliferative malignancies. The
      coding region of the NF-1 gene was analyzed by real-time polymerase chain
      reaction and direct sequencing. Multiplex ligation-dependent probe amplification
      was performed to detect the number of mutant copies. The NF1 gene analysis showed
      the following alterations: mosaic duplication of NF1, TRAF4, and MYO1D.
      Fluorescence in situ hybridization using probes (RP5-1002G3 and RP5-92689)
      flanking NF1 gene in 17q11.2 and CEP17 for 17q11.11.1 was performed. There were
      three signals (RP5-1002G3conRP5-92689) in the interphases analyzed and two
      signals (RP5-1002G3conRP5-92689) in 93% of cells. These findings show a tandem
      duplication of 17q11.2. Conclusion. The case suggests the possibility that NF1
      gene duplication may be associated with a phenotype characterized by
      lymphoproliferative disorders. 

PMID- 25580326
TI  - Corneal bee sting controlled with early surgical intervention and systemic high
      dose steroid therapy.
AB  - A 34-year-old Asian woman presented with painful corneal bee sting. Examinations
      revealed severe corneal swelling with stinger stuck in deep stroma and
      endothelial cell loss. She was treated with early surgery including stinger
      removal and anterior chamber irrigation combined with systemic high-dose steroid
      therapy. Vision and corneal clarity was recovered in 5 days and no additional
      corneal endothelial damage was observed. This report suggests that early surgical
      intervention and high-dose steroid therapy appear to be a useful option in the
      treatment of corneal bee sting. 

PMID- 25580327
TI  - Branch Retinal Artery Occlusion following Dental Extraction.
AB  - Aim. To describe a case of branch retinal artery occlusion following dental
      extraction and to point out the ophthalmic complications of dental procedures to
      ophthalmologists and dentists. Case. A 51-year-old woman was referred to our
      clinic with painless sudden visual loss in her left eye after tooth extraction
      two days ago. In her left eye the best corrected visual acuity was 6/30 and
      fundus examination revealed peripapillary flame-shaped hemorrhages and pale
      retina in the upper temporal arcuate. The right eye examination was unremarkable.
      Conclusion. Dental procedures can lead to miscellaneous ophthalmic complications
      possibly due to the close proximity of the anatomic structures. Retinal arterial
      occlusion is a rare but serious cause of permanent visual loss among these dental
      procedures where the exact pathologic mechanism is still obscure. 

PMID- 25580328
TI  - Epibulbar osseous choristoma.
AB  - The topic of this case report is a rare subconjuctival osseous choristoma that
      corresponded to the left lateral sunconjunctiva and canthus. A 20-year-old man
      was asymptomatic when he arrived for the examination. His full ophthalmic
      examination was normal. Orbital computerized tomography was concordant with
      osseous lesion. Osseous choristomas are the rarest forms of ocular choristomas,
      they are usually being defined as sporadic, and they are found at the superior
      temporal region of the episclera. In our case, choristoma was in the lateral
      canthus of the left eye. We had administered surgical excision by reason of the
      patient's cosmetic requirement. We had noted that the lesion was adherent to
      conjunctiva but not to the sclera and the muscles. After surgical treatment, we
      saw mature heterotrophic osseous tissue in subconjunctival area and Haversian
      canals in compact bone tissue. 

PMID- 25580329
TI  - Macular Hole Progression following Ocriplasmin Intravitreal Injection.
AB  - Ocriplasmin is a protease which has been approved for the treatment of
      symptomatic vitreomacular adhesion (VMA). A 63-year-old presented with blurred
      vision in the left eye and a best corrected visual acuity of 6/18. Optical
      coherence tomography revealed VMA with an underlying macular hole and she
      subsequently underwent a left intravitreal ocriplasmin injection. One week after
      the injection, VMA had been released but with enlargement of the macular hole and
      a drop in her BCVA to 6/60. This persisted at 1 month after the injection. It is
      important to warn patients that ocriplasmin may lead to an enlargement of their
      macular hole with resultant loss in visual acuity. 

PMID- 25580330
TI  - Haemorrhagic lumbar juxtafacet cyst with ligamentum flavum involvement.
AB  - Juxtafacet cysts are an uncommon cause of radiculopathy. They occur most
      frequently in the lumbar region, and their distribution across the spine
      correlates with mobility. Haemorrhagic complications are rare and may occur in
      the absence of any provocation, although there is some association with
      anticoagulation and trauma. We present a case of acute radiculopathy due to an
      L5/S1 juxtafacet cyst with unprovoked haemorrhage which was found to extend into
      ligamentum flavum. The patient underwent uncomplicated microscope assisted
      decompression with excellent results. The demographics, presentation, aetiology,
      and management of juxtafacet cysts are discussed. 

PMID- 25580331
TI  - Delaying shoulder motion and strengthening and increasing achilles allograft
      thickness for glenoid resurfacing did not improve the outcome for a 30-year-old
      patient with postarthroscopic glenohumeral chondrolysis.
AB  - Although interposition soft-tissue (biologic) resurfacing of the glenoid with
      humeral hemiarthroplasty has been considered an option for end-stage glenohumeral
      arthritis, the results of this procedure are highly unsatisfactory in patients
      less than 40 years old. Achilles tendon allograft is popular for glenoid
      resurfacing because it can be made robust by folding it. But one reason that the
      procedure might fail in younger patients is that the graft is not initially thick
      enough for the young active patient. Most authors report folding the graft only
      once to achieve two-layer thickness. We report the case of a 30-year-old male who
      had postarthroscopic glenohumeral chondrolysis that was treated with Achilles
      tendon allograft resurfacing of the glenoid and humeral hemiarthroplasty. An
      important aspect of our case is that the tendon was folded so that it was 50-100%
      thicker than most allograft constructs reported previously. We also used
      additional measures to enhance allograft resiliency and bone incorporation: (1)
      multiple nonresorbable sutures to attach the adjacent graft layers, (2)
      additional resorbable suture anchors and nonresorbable sutures in order to more
      robustly secure the graft to the glenoid, and (3) delaying postoperative motion
      and strengthening. However, despite these additional measures, our patient did
      not have an improved outcome. 

PMID- 25580332
TI  - Bilateral distal femoral nailing in a rare symmetrical periprosthetic knee
      fracture.
AB  - The authors report a case of a 78-year-old polytrauma patient, with severe
      thoracic trauma and bilateral symmetrical periprosthetic femoral fractures after
      a violent car accident. After the primary survey, with the thoracic trauma
      stabilized, neurovascular lesions excluded, and provisional immobilization
      applied, both fractures were classified as OTA: 33-A3, Rorabeck Type II, and
      closed reduction and internal fixation with distal femoral nails were performed.
      At 5 months of follow-up, the patient was able to walk with crutches and clear
      radiologic signs of fracture consolidation could be seen. At 24 months, the
      patient walked without any walking aid and had recovered her previous functional
      status. This surgical option allowed the authors to achieve relative stability
      using an intramedullary technique, preserving fracture hematoma in an osteopenic
      patient, and was found to be successful in recovering the patient's previous
      functional status and satisfaction after major trauma. 

PMID- 25580333
TI  - Knee lymphocutaneous fistula secondary to knee arthroplasty.
AB  - Lower limb lymphorrhea secondary to a surgical procedure is a rare but difficult
      to-solve complication. In lower limb, this entity is frequently associated with
      vascular procedures around the inguinal area. We report on a case of a knee
      lymphocutaneous fistula secondary to a knee revision arthroplasty. To our
      knowledge, no previous reports regarding this complication have been published. 

PMID- 25580334
TI  - Sciatic Nerve Palsy following Total Hip Replacement via Direct Anterior Approach
      after Recommencement of Warfarin for Prophylaxis in Atrial Fibrillation.
AB  - The occurrence of sciatic nerve palsy following posterior and anterolateral
      approaches to the hip has been well documented and is about 1-2%. To our
      knowledge, however, there are no reports of sciatic nerve palsy occurring
      secondary to the anterior approach to the hip for arthroplasty. We describe a
      case of sciatic nerve palsy secondary to haematoma formation following total hip
      replacement through the anterior approach. The recommencement of warfarin for
      prophylaxis against atrial fibrillation is thought to have been a contributing
      factor. Full recovery is rare following delayed diagnosis and early recognition
      of the signs of pain, parasthesia, and gradual loss of dorsiflexion and prompt
      drainage may reverse the condition. We advise caution with restarting warfarin
      following total hip arthroplasty. 

PMID- 25580335
TI  - Symphysis pubis osteomyelitis with bilateral adductor muscles abscess.
AB  - Osteomyelitis of the pubis symphysis is a rare condition. There have been various
      reports in the literature of inflammation and osteomyelitis as well as septic
      arthritis of pubic symphysis. However, due to the fact that these conditions are
      rare and that the usual presenting symptoms are very nonspecific, osteomyelitis
      of the pubic symphysis is often misdiagnosed, thus delaying definitive treatment.
      We present a case that to our knowledge is the first case in literature of
      osteomyelitis of the pubic symphysis in a 17-year-old boy with juvenile
      idiopathic arthritis (JIA), which was initially misdiagnosed and progressed to
      bilateral adductor abscesses. A high suspicion of such condition should be
      considered in a JIA patient who presents with symphysis or thigh pain. 

PMID- 25580336
TI  - Not always asthma: clinical and legal consequences of delayed diagnosis of
      laryngotracheal stenosis.
AB  - Laryngotracheal stenosis (LTS) is a rare condition that occurs most commonly as a
      result of instrumentation of the airway but may also occur as a result of
      inflammatory conditions or idiopathically. Here, we present the case of a patient
      who developed LTS as a complication of granulomatosis with polyangiitis (GPA),
      which was misdiagnosed as asthma for 6 years. After an admission with respiratory
      symptoms that worsened to the extent that she required intubation, a previously
      well 14-year-old girl was diagnosed with GPA. Following immunosuppressive
      therapy, she made a good recovery and was discharged after 22 days. Over
      subsequent years, she developed dyspnoea and "wheeze" and a diagnosis of asthma
      was made. When she became pregnant, she was admitted to hospital with worsening
      respiratory symptoms, whereupon her "wheeze" was correctly identified as
      "stridor," and subsequent investigations revealed a significant subglottic
      stenosis. The delay in diagnosis precluded the use of minimally invasive
      therapies, with the result that intermittent laser resection and open
      laryngotracheal reconstructive surgery were the only available treatment options.
      There were numerous points at which the correct diagnosis might have been made,
      either by proper interpretation of flow-volume loops or by calculation of the
      Empey or Expiratory Disproportion Indices from spirometry data. 

PMID- 25580337
TI  - Osseous choristoma of the tongue: a review of etiopathogenesis.
AB  - Osseous choristoma is a normal bone tissue in an ectopic position. In the oral
      region lingual localization occurs more frequently and the mass is generally
      localized on the dorsum of the tongue. Definitive diagnosis is obtained only
      after histopathologic examination. The etiology remains already debatable. The
      treatment of choice is surgical excision. In this paper we present a case of
      tongue osseous choristoma and a review of the literature. 

PMID- 25580338
TI  - Osteoma of the pharynx that developed from the hyoid bone.
AB  - This paper reports on apparently the first case of a pharyngeal osteoma that
      developed from the hyoid bone. An 84-year-old man's, presenting symptom was a
      slight throat pain. Endoscopic examination revealed a huge mass occluding the
      pharyngeal space. CT scan of the neck showed a large osseous mass adjacent to the
      hyoid bone. Transoral resection with tracheostomy was performed.
      Histopathologically, the tumor consisted of mature lamellar bone without a
      fibrous component. For two years postoperatively, the patient has been free from
      throat symptoms and signs of recurrence. Osteomas are benign, slow-growing
      tumors. They rarely develop symptoms or cause functional disturbance. We
      performed total resection to avoid further functional disturbance as the osteoma
      was huge. To the best of our knowledge, this is the first report on an osteoma
      that occupied the pharyngeal space and developed from the hyoid bone. 

PMID- 25580339
TI  - Management of large erupting complex odontoma in maxilla.
AB  - We present the unusual case of a large complex odontoma erupting in the maxilla.
      Odontomas are benign developmental tumours of odontogenic origin. They are
      characterized by slow growth and nonaggressive behaviour. Complex odontomas,
      which erupt, are rare. They are usually asymptomatic and are identified on
      routine radiograph but may present with erosion into the oral cavity with
      subsequent cellulitis and facial asymmetry. This present paper describes the
      presentation and management of an erupting complex odontoma, occupying the
      maxillary sinus with extension to the infraorbital rim. We also discuss various
      surgical approaches used to access this anatomic area. 

PMID- 25580340
TI  - Perampanel and challenging behaviour in intellectual disability and epilepsy: a
      management dilemma.
AB  - We describe a case of a patient with a diagnosis of moderate learning disability
      with challenging behaviour and treatment refractory epilepsy. Antiepileptics can
      increase challenging behaviour; however, antipsychotics can provoke seizures.
      This results in a difficult balance for patient care. Due to worsening seizures,
      the patient was prescribed perampanel. This increased her aggression and
      agitation resulting in admission. We trialled four antipsychotic drugs to reduce
      her challenging behaviour, two of which worsened her seizures. It was necessary
      to continue antiepileptic medication to maintain adequate seizure control.
      However, the resulting uncontrolled challenging behaviour persisted, meaning she
      was unable to return to her family home on discharge. This case emphasises the
      difficult scenario clinician's encounter when balancing the use of antipsychotics
      and antiepileptics. The case demonstrates the significant functional loss due to
      challenging behaviour, balanced against controlling life threatening seizures. 

PMID- 25580341
TI  - First episode of psychosis in a middle-aged patient with a 14-year history of
      conversion disorder.
AB  - We present a case of a middle-aged male patient with a long history of conversion
      disorder and histrionic personality, who presented with newly onset psychotic
      symptoms while being engaged to treatment with a community mental health team in
      a primary care setting. The symptoms could not be attributed to an organic cause.
      After a short course of olanzapine treatment which caused adverse effects, the
      symptomatology responded well to low dose amisulpride. Conversion symptoms were
      stable throughout the psychotic episode. This case illustrates the complex
      interplay between disorders classified in different categories (somatoform versus
      psychotic disorders). 

PMID- 25580342
TI  - "Peripheral neuropathy crippling bronchial asthma": two rare case reports of
      churg-strauss syndrome.
AB  - Churg-Strauss syndrome (CSS) is a rare cause of vasculitic neuropathy. Although
      rare and potentially fatal, Churg-Strauss syndrome (CSS) is easily diagnosable
      and treatable. The presence of bronchial asthma with peripheral neuropathy in a
      patient alerts a physician to this diagnosis. This is vividly illustrated by the
      presented two cases who had neuropathy associated with bronchial asthma,
      eosinophilia, sinusitis, and positive perinuclear antineutrophil cytoplasmic
      antibodies (p-ANCA) test, which improved with administration of steroids. 

PMID- 25580343
TI  - Pulmonary Cement Embolism following Percutaneous Vertebroplasty.
AB  - Percutaneous vertebroplasty is a minimal invasive procedure that is applied for
      the treatment of osteoporotic vertebral fractures. During vertebroplasty, the
      leakage of bone cement outside the vertebral body leads to pulmonary cement
      embolism, which is a serious complication of this procedure. Here we report a 48
      year-old man who was admitted to our hospital with dyspnea after percutaneous
      vertebroplasty and diagnosed as pulmonary cement embolism. 

PMID- 25580344
TI  - Evaluation of suspected aspirated beverage can pull tab: radiographs may not be
      enough.
AB  - A 67-year-old male presented to the emergency department with concern for
      accidental aspiration of an aluminum beverage can pull tab. Neck and chest
      radiographs did not reveal an aspirated foreign body. Despite ongoing complaint
      of dysgeusia and adamancy of aspiration by the patient, he was discharged to home
      without recommendation for further follow-up. Seven months later, a computed
      tomography (CT) scan of the chest performed as part of an unrelated lung cancer
      work up confirmed the presence of a left mainstem bronchus metallic foreign body
      compatible with a pull tab. This case report illustrates the poor negative
      predictive value of radiographs for a suspected aluminum foreign body and
      demonstrates the superiority of CT for this purpose. In such presentations it is
      imperative to have a low threshold for performing further diagnostic evaluation
      with CT due to the relatively high radiolucency of aluminum. 

PMID- 25580345
TI  - A Rare Case of Pulmonary Atresia with Ventricular Septal Defect with a Right
      Sided Aortic Arch and a Calcified Pulmonary AVM Presenting in an Adult without
      Cyanosis.
AB  - Pulmonary atresia with ventricular septal defect (PA-VSD) with pulmonary arterial
      supply arising from the aorta representing large MAPCAs associated with a right
      sided aortic arch is an uncommon anomaly. Most of the patients succumb to severe
      respiratory compromise or congestive cardiac failure very early. We report the
      clinical details and imaging findings of a case of PA-VSD with a right sided
      aortic arch and a calcified pulmonary arteriovenous malformation (AVM) in a 21
      year-old postpartum female with no previous episodes of cyanosis who was
      diagnosed as having a cardiac anomaly on echocardiography when she presented with
      breathlessness during the 8th month of the pregnancy. 

PMID- 25580346
TI  - Gossypiboma posing as a diagnostic dilemma: a case report and review of the
      literature.
AB  - The term gossypiboma is used to describe a retained surgical sponge after
      operation. It is a rare but serious complication which is seldom reported because
      of the medicolegal implications. Gossypiboma usually has varied and vague
      presentation and is also difficult to detect on radiological investigations. It
      can even remain silent and present years after the operation. We report a case of
      a 38-year-old lady who presented with vague pain and chronic lump in the right
      iliac fossa region. She had a history of cesarean section 4 years ago.
      Radiological investigations were inconclusive in detecting the retained sponge. A
      working diagnosis of mesenteric cyst was made and an exploratory laparotomy was
      done where she was found to have a large gossypiboma densely adhered to the small
      bowel and surrounding structures. Though rare, gossypiboma should be kept in mind
      as a differential diagnosis in postoperative cases presenting as vague pain or
      chronic lump even years after the operation. 

PMID- 25580347
TI  - A symptomatic de novo pheochromocytoma 23 years after liver transplantation: a
      case report and review of the literature.
AB  - We report a case of subacute onset of headaches and tremors with a newly
      discovered adrenal pheochromocytoma 23 years after an orthotopic liver
      transplantation and provide a review of the scarce literature regarding endocrine
      malignancies in liver transplant recipients. We describe the clinical
      presentation, diagnostic work-up, and management. This is the second case report
      in the literature of a de novo pheochromocytoma after solid organ
      transplantation. It shows that new-onset common symptoms in transplant recipients
      are always challenging and deserve a very thorough work-up until the cause of the
      symptoms is elucidated. A broad differential diagnosis should always be included
      in the study of any abnormalities in this patient population. 

PMID- 25580348
TI  - Intrascrotal dedifferentiated leiomyosarcoma originating from dartos muscle.
AB  - A 46-year-old man, who had visited our hospital complaining of a small
      intrascrotal nodule ten years ago, returned to us because of the rapid growth of
      the nodule. Computed tomography revealed a heterogeneously enhanced intrascrotal
      tumor of approximately 4 * 3 cm. The tumor and the right testis were excised with
      the adhered right scrotal skin. The pathological diagnosis was pleomorphic
      leiomyosarcoma with dedifferentiation originating from the dartos muscle.
      Urological dedifferentiated leiomyosarcomas are rarely reported and the clinical
      features are mostly unknown. This is the first report to describe the
      dedifferentiated leiomyosarcoma of the dartos muscle. 

PMID- 25580349
TI  - Sociodemographic Determinants of Malaria among Under-Five Children in Ghana.
AB  - Background. Malaria is an entrenched global health challenge particularly in the
      sub-Saharan African countries. However, in Ghana, little is known about the
      determinants of malaria prevalence among under-five children. As such, this study
      sought to examine the sociodemographic factors that determine malaria among under
      five children in Ghana. Methods. This paper used secondary data drawn from the
      2008 Ghana Demographic and Health Survey. Bivariate analysis and complementary
      log-log regression models were used to examine the determinants of malaria
      prevalence among under-five children in Ghana for the study period. Results. The
      results therefore revealed that region of residence, age of child, and ownership
      of mosquito net were the key predictors of malaria cases among under-five
      children in Ghana for the five-year period preceding the survey. Conclusion. It
      is therefore imperative that special education on prevention of malaria should be
      intensified by the National Malaria Control Programme in all the regions in order
      to reduce malaria prevalence particularly among under-five children in Ghana. 

PMID- 25580351
TI  - Bioinformatic Identification of Peptidomimetic-Based Inhibitors against
      Plasmodium falciparum Antigen AMA1.
AB  - Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a valuable vaccine
      candidate and exported on the merozoite surface at the time of erythrocyte
      invasion. PfAMA1 interacts with rhoptry neck protein PfRON2, a component of the
      rhoptry protein complex, which forms the tight junction at the time of invasion.
      Phage display studies have identified a 15-residue (F1) and a 20-residue (R1)
      peptide that bind to PfAMA1 and block the invasion of erythrocytes. Cocrystal
      structures of central region of PfAMA1 containing disulfide-linked clusters
      (domains I and II) with R1 peptide and a peptide derived from PfRON2 showed
      strong structural similarity in binding. The peptides bound to a hydrophobic
      groove surrounded by domain I and II loops. In this study, peptidomimetics based
      on the crucial PfAMA1-binding residues of PfRON2 peptide have been identified.
      Top 5 peptidomimetics when checked for their docking on the region of PfAMA1
      encompassing the hydrophobic groove were found to dock on the groove. Drug-like
      molecules having structural similarity to the top 5 peptidomimetics were
      identified based on their binding ability to PfAMA1 hydrophobic groove in blind
      docking. These inhibitors provide potential lead compounds, which could be used
      in the development of antimalarials targeting PfAMA1. 

PMID- 25580350
TI  - Exploiting unique structural and functional properties of malarial glycolytic
      enzymes for antimalarial drug development.
AB  - Metabolic enzymes have been known to carry out a variety of functions besides
      their normal housekeeping roles known as "moonlighting functions." These
      functionalities arise from structural changes induced by posttranslational
      modifications and/or binding of interacting proteins. Glycolysis is the sole
      source of energy generation for malaria parasite Plasmodium falciparum, hence a
      potential pathway for therapeutic intervention. Crystal structures of several P.
      falciparum glycolytic enzymes have been solved, revealing that they exhibit
      unique structural differences from the respective host enzymes, which could be
      exploited for their selective targeting. In addition, these enzymes carry out
      many parasite-specific functions, which could be of potential interest to control
      parasite development and transmission. This review focuses on the moonlighting
      functions of P. falciparum glycolytic enzymes and unique structural differences
      and functional features of the parasite enzymes, which could be exploited for
      therapeutic and transmission blocking interventions against malaria. 

PMID- 25580352
TI  - Outcome determinants of stroke in a brazilian primary stroke center.
AB  - Background. Stroke mortality in Brazil is one of the highest among Western
      countries. Nonetheless, stroke outcome determinants are still poorly known in
      this country. In this study we evaluate outcome determinants of stroke in a
      primary stroke center in Sao Paulo, Brazil. Methods. We evaluated demographic,
      clinical, and outcome data of patients with ischemic stroke (IS), transient
      ischemic attack (TIA), and intracerebral hemorrhage (ICH) admitted at "Hospital
      Paulistano," Sao Paulo, Brazil. In-hospital mortality and functional outcome
      determinants were assessed. Univariate and binary logistic regression analysis
      were performed. Results. Three hundred forty-one patients were included in the
      study, 52.2% being male with 66.8 +/- 15.7 years. The stroke type distribution
      was IS: 59.2%, TIA: 29.6%, and ICH: 11.1%. ICH was associated with greater
      severity and poorer functional outcome. The determinants of poorer functional
      outcome were higher NIHSS, lower Glasgow score, and lower oxygen saturation
      level. The most important mortality determinant was the presence of visual
      symptoms. Conclusions. The stroke mortality and stroke outcome determinants found
      in the present study do not remarkably differ from studies carried out in
      developed countries. Stroke prognosis studies are crucial to better understand
      the high burden of stroke in Brazil. 

PMID- 25580353
TI  - The value of postoperative serum carcinoembryonic antigen and carbohydrate
      antigen 19-9 levels for the early detection of gastric cancer recurrence after
      curative resection.
AB  - PURPOSE: This study aimed to evaluate the value of serum carcinoembryonic antigen
      (CEA) and carbohydrate antigen 19-9 (CA19-9) levels to detect gastric cancer
      recurrence. MATERIALS AND METHODS: We retrospectively reviewed 154 patients who
      developed recurrence within 2 years after curative gastric cancer surgery and
      analyzed the relationship between postoperative CEA and CA19-9 levels and
      recurrence. We readjusted the cut-off values to improve the detection of
      recurrence. Subgroup analysis according to clinicopathologic variables was
      performed to further investigate the relationship between recurrence and CEA and
      CA19-9 levels. RESULTS: The sensitivity and specificity for elevated CEA levels
      to detect recurrence were 40.6% and 89.5%, respectively, and those for CA19-9
      were 34.2% and 93.6%, respectively. The sensitivity and specificity for elevation
      of either tumor marker were 54.3% and 84.0%, respectively; those for elevation of
      both tumor markers were 19.2% and 98.4%, respectively. By readjusting the cut-off
      values from 5.0 ng/ml to 5.2 ng/ml for CEA and from 37.00 U/ml to 30.0 U/ml for
      CA19-9, the sensitivity was increased from 34.2% to 40.2% for CA19-9, while there
      was no increase in sensitivity for CEA. In subgroup analysis, the sensitivity of
      CEA was higher in patients with elevated preoperative CEA levels than in patients
      with normal preoperative CEA levels (86.7% versus 33.7%; P<0.001). Furthermore,
      the sensitivity of CA19-9 was higher in patients with elevated preoperative CA19
      9 levels than in patients with normal preoperative CA19-9 levels (82.61% versus
      26.83%; P<0.001). CONCLUSIONS: CEA and/or CA19-9 measurement with the readjusted
      cut-off values allows for more effective detection of gastric cancer recurrence.

PMID- 25580354
TI  - Uncut Roux-en-Y Reconstruction after Laparoscopic Distal Gastrectomy Can Be a
      Favorable Method in Terms of Gastritis, Bile Reflux, and Gastric Residue.
AB  - PURPOSE: Laparoscopic distal gastrectomy (LDG) is a well-established procedure
      for the treatment of early gastric cancer. Several reconstruction methods can be
      adopted after LDG according to tumor characteristics and surgeon preference. This
      study aimed to compare the remnant gastric functions after different
      reconstructions. MATERIALS AND METHODS: In total, 221 patients who underwent LDG
      between March 2005 and October 2013 were reviewed retrospectively. The patients
      were classified into four groups based on the reconstructive procedure: Billroth
      I (BI) anastomosis, Billroth II (BII) with Braun anastomosis, Roux-en-Y (RY)
      reconstruction, or uncut RY reconstruction. Patient demographics, surgical
      outcomes, and postoperative endoscopic findings were reviewed and compared among
      groups. RESULTS: Endoscopic evaluations at 11.8+/-3.8 months postoperatively
      showed less frequent gastritis and bile reflux in the remnant stomach in the RY
      group compared to the BI and BII groups. There was no significant difference in
      the gastric residue among the BI, BII, and RY groups. The incidence of gastritis
      and bile reflux in the uncut RY group was similar to that in the RY group, while
      residual gastric content in the uncut RY group was significantly smaller and less
      frequently observed than that in the RY group (5.8% versus 35.3%, P=0.010).
      CONCLUSIONS: RY and uncut RY reconstructions are equally superior to BI and BII
      with Braun anastomoses in terms of gastritis and bile reflux in the remnant
      stomach. Furthermore, uncut RY reconstruction showed improved stasis compared to
      conventional RY gastrojejunostomy. Uncut RY reconstruction can be a favorable
      reconstructive procedure after LDG.

PMID- 25580355
TI  - Impact of age on clinicopathological features and survival of patients with
      noncardia gastric adenocarcinoma.
AB  - PURPOSE: Gastric cancer often occurs in the elderly but is uncommon in young
      individuals. Whether young patients have different clinical behaviors and
      outcomes from those of older patients remain unclear. MATERIALS AND METHODS: We
      identified 1,366 cases of newly diagnosed noncardia gastric adenocarcinoma from
      the Kaiser Permanente Northern California Cancer Registry between 2000 and 2010.
      We then compared the clinicopathological features and survival among the
      different age groups. RESULTS: The male : female ratio differed significantly
      between the younger and older patient groups (0.84 in age <50 years vs. 1.52>60
      years, P<0.01). More younger patients were Hispanic (54% patients <40 years vs.
      19% patients >=70 years, P<0.0001), while more older patients were Caucasian (49%
      patients >=70 years vs. 15% patients <40 years; P<0.0001). The diffuse/mixed
      histological type was more prevalent in younger patients (70% patients <40 years
      vs. 27% patients >=70 years; P<0.0001), whereas the intestinal type was more
      frequent in older patients (71% in patients >=70 years vs. 30% in patients <40
      years; P<0.0001). Poorly differentiated adenocarcinoma was more common in the
      younger patients (80% in patients <40 years vs. 60% in patients >=70 years;
      P=0.016). Survival rates at 1, 2, and 5 years gradually declined with increasing
      age (overall P=0.0002). CONCLUSIONS: Young patients with gastric cancer had more
      aggressive disease but higher overall survival rates than older patients. Younger
      Hispanic patients and older Caucasian patients were more likely to be diagnosed
      with gastric cancer. These differences may be due to biological predisposition
      and/or environmental exposure.

PMID- 25580356
TI  - Long-Term Outcomes of Proximal Gastrectomy versus Total Gastrectomy for Upper
      Third Gastric Cancer.
AB  - PURPOSE: There are two surgical procedures for proximal early gastric cancer
      (EGC): total gastrectomy (TG) and proximal gastrectomy (PG). This study aimed to
      compare the long-term outcomes of PG with those of TG. MATERIALS AND METHODS:
      Between January 2001 and December 2008, 170 patients were diagnosed with proximal
      EGC at Soonchunhyang University Cheonan Hospital, of which 64 patients underwent
      PG and 106 underwent TG. Clinicopathologic features, postoperative complications,
      blood chemistry data, changes in body weight, and oncological outcomes were
      analyzed and retrospectively compared between both groups. RESULTS: Tumor size
      was smaller and the number of retrieved lymph nodes was lower in the PG group.
      The postoperative complication rate was 10.9% in the TG group and 16.9% in the PG
      group. The incidence of Los Angeles grade C and D reflux esophagitis was
      significantly higher in the TG group. Hemoglobin level was higher and body weight
      loss was greater in the TG group at 2, 3, and 5 years postoperatively. The
      albumin levels at 3 and 5 years were lower in the TG group. There was no
      significant difference in the 5-year overall survival rates between the two
      groups (P=0.789). CONCLUSIONS: Postoperative complications and oncologic outcomes
      were observed to be similar between the two groups. The PG group showed better
      laboratory data and weight loss than did the TG group. Moreover, severe reflux
      esophagitis occurred less frequently in the PG group than in the TG group. PG can
      be considered as an effective surgical treatment for proximal EGC.

PMID- 25580357
TI  - Impact of Intraoperative Macroscopic Diagnosis of Serosal Invasion in
      Pathological Subserosal (pT3) Gastric Cancer.
AB  - PURPOSE: The macroscopic diagnosis of tumor invasion through the serosa during
      surgery is not always distinct in patients with gastric cancer. The prognostic
      impact of the difference between macroscopic findings and pathological diagnosis
      of serosal invasion is not fully elucidated and needs to be re-evaluated.
      MATERIALS AND METHODS: A total of 370 patients with locally advanced pT2 to pT4a
      gastric cancer who underwent curative surgery were enrolled in this study. Among
      them, 155 patients with pT3 were divided into three groups according to the
      intraoperative macroscopic diagnosis of serosal invasion, as follows: serosa
      exposure (SE)(-) (no invasion, 72 patients), SE(+/-) (ambiguous, 47 patients),
      and SE(+) (definite invasion, 36 patients), and the clinicopathological features,
      surgical outcomes, and disease-free survival (DFS) were analyzed. RESULTS: A
      comparison of the 5-year DFS between pT3_SE(-) and pT2 groups and between
      pT3_SE(+) and pT4a groups revealed that the differences were not statistically
      significant. In addition, in a subgroup analysis of pT3 patients, the 5-year DFS
      was 75.1% in SE(-), 68.5% in SE(+/-), and 39.4% in SE(+) patients (P<0.05). In a
      multivariate analysis to evaluate risk factors for tumor recurrence, macroscopic
      diagnosis (hazard ratio [HR], SE(-) : SE(+/-) : SE(+)=1 : 1.01 : 2.45, P=0.019)
      and lymph node metastasis (HR, N0 : N1 : N2 : N3=1 : 1.45 : 2.20 : 9.82, P<0.001)
      were independent risk factors for recurrence. CONCLUSIONS: Gross inspection of
      serosal invasion by the surgeon had a strong impact on tumor recurrence in
      gastric cancer patients. Consequently, the gross appearance of serosal invasion
      should be considered as a factor for predicting patients' prognosis.

PMID- 25580358
TI  - Survival analysis of gastric cancer patients with incomplete data.
AB  - PURPOSE: Survival analysis of gastric cancer patients requires knowledge about
      factors that affect survival time. This paper attempted to analyze the survival
      of patients with incomplete registered data by using imputation methods.
      MATERIALS AND METHODS: Three missing data imputation methods, including
      regression, expectation maximization algorithm, and multiple imputation (MI)
      using Monte Carlo Markov Chain methods, were applied to the data of cancer
      patients referred to the cancer institute at Imam Khomeini Hospital in Tehran in
      2003 to 2008. The data included demographic variables, survival times, and
      censored variable of 471 patients with gastric cancer. After using imputation
      methods to account for missing covariate data, the data were analyzed using a Cox
      regression model and the results were compared. RESULTS: The mean patient
      survival time after diagnosis was 49.1+/-4.4 months. In the complete case
      analysis, which used information from 100 of the 471 patients, very wide and
      uninformative confidence intervals were obtained for the chemotherapy and surgery
      hazard ratios (HRs). However, after imputation, the maximum confidence interval
      widths for the chemotherapy and surgery HRs were 8.470 and 0.806, respectively.
      The minimum width corresponded with MI. Furthermore, the minimum Bayesian and
      Akaike information criteria values correlated with MI (-821.236 and -827.866,
      respectively). CONCLUSIONS: Missing value imputation increased the estimate
      precision and accuracy. In addition, MI yielded better results when compared with
      the expectation maximization algorithm and regression simple imputation methods.

PMID- 25580359
TI  - The result of conversion surgery in gastric cancer patients with peritoneal
      seeding.
AB  - PURPOSE: Palliative gastrectomy and chemotherapy are important options for
      peritoneal seeding of gastric cancer. The treatment stage IV gastric cancer
      patient who respond to induction chemotherapy, is converted to gastrectomy
      (conversion therapy or conversion surgery). This study explored the clinical
      outcomes of gastric cancer patients with peritoneal seeding who had undergone
      conversion therapy. MATERIALS AND METHODS: Between 2003 and 2012, gastric cancer
      patients with peritoneal seeding, as determined by preoperative or intraoperative
      diagnosis were reviewed retrospectively. Clinicopathologic characteristics and
      clinical outcomes of patients with peritoneal seeding were analyzed. RESULTS:
      Forty-three patients were enrolled. Eighteen patients had undergone conversion
      surgery and 25 patients continued conventional chemotherapy. Among the 18
      conversion patients, 10 received clinically curative resection. The median follow
      up period was 28.5 months (range 8 to 60 months) and the total 3-year survival
      rate was 16.3%. The median survival time of the patients who received clinically
      curative conversion therapy was 37 months, and the 3-year survival rate was 50%.
      The median follow-up for non-curative gastrectomy patients was 18 months. No
      patient treated using chemotherapy survived to 3 years; the median survival time
      was 8 months. The differences in survival time between the groups was
      statistically significant (P<0.001). CONCLUSIONS: In terms of survival benefits
      for gastric cancer patients with peritoneal seeding, clinically curative
      conversion therapy resulted in better clinical outcomes.

PMID- 25580360
TI  - A rare presentation of metastasis of prostate adenocarcinoma to the stomach and
      rectum.
AB  - Prostate cancer is the second most common cause of cancer death in men in the
      United States. The most common sites of metastasis include the bone, lymph nodes,
      lung, liver, pleura, and adrenal glands, whereas metastatic prostate cancer
      involving the gastrointestinal tract has been rarely reported. A 64-year-old
      African-American man with a history of prostate cancer presented with anemia. He
      reported the passing of dark colored stools but denied hematemesis or
      hematochezia. Colonoscopy revealed circumferential nodularity, and histology
      demonstrated metastatic carcinoma of the prostate. Esophagogastroduodenoscopy
      showed hypertrophic folds in the gastric fundus, and microscopic examination
      revealed tumor cells positive for prostate-specific antigen. Bone scanning and
      computed tomography of the abdomen and pelvis did not show metastasis. It is
      crucial to distinguish primary gastrointestinal cancer from metastatic lesions,
      especially in patients with a history of cancer at another site, for appropriate
      management. 

PMID- 25580361
TI  - Gastric cancer presenting as a krukenberg tumor at 22 weeks' gestation.
AB  - Gastric cancer is rare during pregnancy, and often advanced upon presentation. A
      Krukenberg tumor presents a diagnostic and therapeutic challenge in the pregnant
      patient. We present a case of a 38-year-old woman at 22 weeks' gestation who
      presented with worsening epigastric pain, and was found to have a left pelvic
      mass on ultrasound, which was confirmed by magnetic resonance imaging. She went
      into active labor and delivered a viable infant via vaginal delivery. An
      exploratory laparotomy revealed a large mass originating from her left ovary and
      diffuse thickening of the lesser curvature of the stomach. Frozen section
      investigation revealed the presence of signet cell adenocarcinoma. Subsequent
      upper endoscopy showed linitis plastica, while biopsy confirmed the presence of
      adenocarcinoma. In conclusion, the occurrence of gastric cancer in pregnancy is
      rare despite extremely common symptoms. The management poses a challenge because
      of the need for early treatment, and the continuation of the pregnancy. 

PMID- 25580362
TI  - Primary gastric malignant melanoma mimicking adenocarcinoma.
AB  - We report a case of primary gastric malignant melanoma that was diagnosed after
      curative resection but initially misdiagnosed as adenocarcinoma. A 68-year-old
      woman was referred to our department for surgery for gastric adenocarcinoma
      presenting as a polypoid lesion with central ulceration located in the upper body
      of the stomach. The preoperative diagnosis was confirmed by endoscopic biopsy. We
      performed laparoscopic total gastrectomy, and the final pathologic evaluation led
      to the diagnosis of primary gastric malignant melanoma without a primary lesion
      detected in the body. To the best of our knowledge, primary gastric malignant
      melanoma is extremely rare, and this is the first case reported in our country.
      According to the literature, it has aggressive biologic activity compared with
      adenocarcinoma, and curative resection is the only promising treatment strategy.
      In our case, the patient received an early diagnosis and underwent curative
      gastrectomy with radical lymphadenectomy, and no recurrence was noted for about
      two years. 

PMID- 25580363
TI  - Inflammatory leukocyte phenotypes correlate with disease progression in
      idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by progressive deposition of
      extracellular matrix, worsening dyspnea, and eventual mortality. Pathogenesis of
      IPF is poorly understood and the role inflammation and activated leukocytes play
      in the disease process is controversial. Previous studies demonstrated that
      activated leukocyte subsets characterize IPF patients. We sought to validate this
      observation in a well-defined cohort of 35 IPF patients and to correlate the
      observed leukocyte phenotypes with robust parameters of disease progression. We
      demonstrate that in univariate and multivariate analyses, increases in the
      CD14hi, CD16hi subset of monocytes measured at baseline correlated with disease
      progression, with a threshold value >0.5% of the total peripheral blood
      mononuclear cells being a significant predictor for worse outcome. In addition,
      several T cell subsets, including CD25 expressing CD4 cells, and CXCR3 expressing
      CD4 and CD8 subsets correlated with disease progression when found in increased
      percentages in the peripheral blood of IPF patients when sampled at baseline.
      Somewhat surprising in comparison to previous literature, the CD4 T cells did not
      appear to have lost expression of the co-stimulatory molecule, CD28, but the CD8
      T cells did. Taken together, these results are consistent with the presence of an
      inflammatory process in IPF patients who eventually progress. However, when
      longitudinal measurements of these same markers were examined, there was
      significant heterogeneity of expression and these biomarkers did not necessarily
      remain elevated in IPF patients with progressive disease. We interpret this
      heterogeneity to suggest that IPF patients experience episodic inflammatory
      events that once triggered, may lead to disease progression. This longitudinal
      heterogeneity in biomarker analyses may explain why such markers are not
      consistently measured in all IPF cohorts.

PMID- 25580364
TI  - Palladium-Catalyzed C8-Selective C-H Arylation of Quinoline N-Oxides: Insights
      into the Electronic, Steric and Solvation Effects on the Site-Selectivity by
      Mechanistic and DFT Computational Studies.
AB  - We report herein a palladium-catalyzed C-H arylation of quinoline N-oxides that
      proceeds with high selectivity in favor of the C8-isomer. This site-selectivity
      is unusual for palladium, since all of the hitherto described methods of
      palladium-catalyzed C-H functionalization of quinoline N-oxides are highly C2
      selective. The reaction exhibits a broad synthetic scope with respect to
      quinoline N-oxides and iodoarenes and can be significantly accelerated to sub
      hour reaction times under microwave irradiation. The C8-arylation method can be
      carried out on gram scale and has excellent functional group tolerance.
      Mechanistic and Density Functional Theory (DFT) computational studies provide
      evidence for the cyclopalladation pathway and describe key parameters influencing
      the site-selectivity.

PMID- 25580365
TI  - Changes in Body Mass Index Following HAART Initiation among HIV-Infected Women in
      the Women's Interagency HIV Study.
AB  - OBJECTIVE: Examine changes in, and factors associated with changing body mass
      index (BMI) in women following highly active antiretroviral therapy (HAART)
      initiation. METHODS: 1177 HIV-infected Women's Interagency HIV Study participants
      who contributed 10,754 years of follow-up following HAART initiation were
      studied. Changes in median BMI up to 15 years following HAART initiation, and the
      highest and lowest BMI reached following HAART initiation were summarized by pre
      HAART BMI category (<18.5 [underweight], 18.5-<25.0 [normal weight], 25.0-<30.0
      [overweight], 30.0-<40.0 [obese], and >= 40.0 [morbidly obese]). Multivariate
      mixed effects ordinal logistic regression estimated the degree of association of
      each exposure of interest with post-HAART BMI. RESULTS: Before HAART, 39% percent
      of women had normal BMI, 31% were overweight, 23% were obese, and 5% were
      morbidly obese. Following HAART initiation, median BMI change (per 5 years) was
      0.21 kg/m2 (90% confidence interval [CI]: -1.33, 0.42) for those with normal pre
      HAART BMI, 0.39 kg/m2 (90% CI: 0.15,0.66) for overweight, 0.31 kg/m2 (90% CI: 
      1.18,0.67) for obese, and -0.36kg/m2 for morbidly obese women. After initiating
      HAART, 40% with normal pre-HAART BMI became overweight at some point; of those
      overweight, 46% remained overweight and 47% became obese; 71% of obese women
      remained obese and 27% became morbidly obese. Each year of nucleoside analog
      reverse transcriptase inhibitor use was associated with a 3% decreased odds of
      reaching a higher BMI category (OR 0.97, 95% CI: 0.95, 0.99), while each year of
      protease inhibitor or non-nucleoside analog reverse transcriptase inhibitor use
      were associated with a 6% (OR 1.06, 95% CI: 1.04, 1.08) and 5%(OR 1.05, 95% CI:
      1.01, 1.08) increased odds of having a higher BMI category, respectively.
      CONCLUSIONS: Although overweight and obesity are highly prevalent in this large
      cohort of HIV-infected, minority women, HAART use was associated with only a
      modest increase in BMI over time.

PMID- 25580366
TI  - Cancer Incidence in HIV-Infected Versus Uninfected Veterans: Comparison of Cancer
      Registry and ICD-9 Code Diagnoses.
AB  - BACKGROUND: Given the growing interest in the cancer burden in persons living
      with HIV/AIDS, we examined the validity of data sources for cancer diagnoses
      (cancer registry versus International Classification of Diseases, Ninth Revision
      [ICD-9 codes]) and compared the association between HIV status and cancer risk
      using each data source in the Veterans Aging Cohort Study (VACS), a prospective
      cohort of HIV-infected and uninfected veterans from 1996 to 2008. METHODS: We
      reviewed charts to confirm potential incident cancers at four VACS sites. In the
      entire cohort, we calculated cancer-type-specific age-, sex-, race/ethnicity-,
      and calendar-period-standardized incidence rates and incidence rate ratios (IRR)
      (HIV-infected versus uninfected). We calculated standardized incidence ratios
      (SIR) to compare VACS and Surveillance, Epidemiology, and End Results rates.
      RESULTS: Compared to chart review, both Veterans Affairs Central Cancer Registry
      (VACCR) and ICD-9 diagnoses had approximately 90% sensitivity; however, VACCR had
      higher positive predictive value (96% versus 63%). There were 6,010 VACCR and
      13,386 ICD-9 incident cancers among 116,072 veterans. Although ICD-9 rates tended
      to be double VACCR rates, most IRRs were in the same direction and of similar
      magnitude, regardless of data source. Using either source, all cancers combined,
      most viral-infection-related cancers, lung cancer, melanoma, and leukemia had
      significantly elevated IRRs. Using ICD-9, eight additional IRRs were
      significantly elevated, most likely due to false positive diagnoses. Most ICD-9
      SIRs were significantly elevated and all were higher than the corresponding VACCR
      SIR. CONCLUSIONS: ICD-9 may be used with caution for estimating IRRs, but should
      be avoided when estimating incidence or SIRs. Elevated cancer risk based on VACCR
      diagnoses among HIV-infected veterans was consistent with other studies.

PMID- 25580367
TI  - Carnitine Palmitoyltransferase 1b Deficient Mice Develop Severe Insulin
      Resistance After Prolonged High Fat Diet Feeding.
AB  - BACKGROUND: Carnitine palmitoyltransferase 1 (CPT1) is the rate-limiting enzyme
      governing the entry of long-chain acyl-CoAs into mitochondria. Treatments with
      CPT1 inhibitors protect against insulin resistance in short-term preclinical
      animal studies. We recently reported that mice with muscle isoform CPT1b
      deficiency demonstrated improved insulin sensitivity when fed a High Fat-Diet
      (HFD) for up to 5 months. In this follow up study, we further investigated
      whether the insulin sensitizing effects of partial CPT1b deficiency could be
      maintained under a prolonged HFD feeding condition. METHODS: We investigated the
      effects of CPT1b deficiency on HFD-induced insulin resistance using heterozygous
      CPT1b deficient (Cpt1b+/-) mice compared with Wild Type (WT) mice fed a HFD for a
      prolonged period of time (7 months). We assessed insulin sensitivity using
      hyperinsulinemic-euglycemic clamps. We also examined body composition, skeletal
      muscle lipid profile, and changes in the insulin signaling pathways of skeletal
      muscle, liver, and adipose tissue. RESULTS: We found that Cpt1b+/- mice became
      severely insulin resistant after 7 months of HFD feeding. Cpt1b+/- mice exhibited
      a substantially reduced glucose infusion rate and skeletal muscle glucose uptake.
      While Cpt1b+/- mice maintained a slower weight gain with less fat mass than WT
      mice, accumulation of lipid intermediates became evident in the muscle of Cpt1b+/
      but not WT mice after 7 months of HFD feeding. Insulin signaling was impaired in
      the Cpt1b+/- as compared to the WT muscles. CONCLUSION: Partial CPT1b deficiency,
      mimicking CPT1b inhibition, may lead to impaired insulin signaling and insulin
      sensitivity under a prolonged HFD feeding condition. Therefore, further studies
      on the potential detrimental effects of prolonged therapy with CPT1 inhibition
      are necessary in the development of this potential therapeutic strategy.

PMID- 25580368
TI  - Radiobiological Modeling Based on 18F-Fluorodeoxyglucose Positron Emission
      Tomography Data for Esophageal Cancer.
AB  - BACKGROUND: We investigated the relationship of standardized uptake values (SUVs)
      to radiobiological parameters, such a 25 s tumor control probability (TCP), to
      allow for quantitative prediction of tumor response based on SUVs from 18F
      fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) before and after
      treatment for esophageal cancer. METHODS: We analyzed data from 20 esophageal
      cancer patients treated with chemoradiotherapy (CRT) followed by surgery. Tumor
      pathologic response to CRT was assessed in surgical specimens. Patients underwent
      18F-FDG PET imaging before and after CRT. Rigid image registration was performed
      between both images. Because TCP in a heterogeneous tumor is a function of
      average cell survival, we modeled TCP as a function of <SUVR>, a possible
      surrogate for average cell survival (<SUVR>=<SUVafter/SUVbefore>). TCP was
      represented by a sigmoid function with two parameters: SUVR50, the <SUVR> at
      which TCP=0.5, and gamma50, the slope of the curve at SUVR50. The two parameters
      and their confidence intervals (CIs) were estimated using the maximum-likelihood
      method. The correlation between SUV before CRT and SUV change <SUVbefore -
      SUVafter> was also studied. RESULTS: A TCP model as a function of SUV before and
      after treatment was developed for esophageal cancer patients. The maximum
      likelihood estimate of SUVR50 was 0.47 (90% CI, 0.30-0.61) and for gamma50 was
      1.62 (90% CI, 0-4.2). High initial SUV and larger metabolic response (larger
      <SUVbefore -SUVafter>) were correlated, and this correlation was stronger among
      responders. CONCLUSIONS: Our TCP model indicates that <SUVafter/SUVbefore> is a
      possible surrogate for cell survival in esophageal cancer patients. Although CIs
      are large as a result of the small patient sample, parameters for a TCP curve can
      be derived and an individualized TCP can be calculated for future patients.
      Initial SUV does not predict response, whereas a correlation is found between
      surrogates for initial tumor burden and cell kill during therapy.

PMID- 25580371
TI  - Facile Preparation of Nanogels Using Activated Ester Containing Polymers.
AB  - A facile methodology to prepare water-dispersible nanogels based on
      pentafluorophenyl acrylate and polyethylene glycol methacrylate random copolymer
      and diamine cross-linkers has been developed. Cross-linking reaction was
      characterized by FTIR and 19F NMR. We show that those nanogels : (i) are water
      dispersible; (ii) can conveniently encapsulate lipophilic guest molecules; (iii)
      can be prepared with different nanosizes; (iv) are engineered to allow for
      surface decoration with additional functional groups.

PMID- 25580369
TI  - Regulation of T-cell Tolerance by Lymphatic Endothelial Cells.
AB  - Lymphatic endothelial cells are most often thought of as structural cells that
      form the lymphatic vasculature, which transports fluid out of peripheral tissues
      and transports antigens and antigen presenting cells to lymph nodes. Recently, it
      has been shown that lymphatic endothelial cells also dynamically respond to and
      influence the immune response in several ways. Here, we describe how lymphatic
      endothelial cells induce peripheral T-cell tolerance and how this relates to
      tolerance induced by other types of antigen presenting cells. Furthermore, the
      ability of lymphatic endothelial cells to alter immune responses under steady
      state or inflammatory conditions is explored, and the therapeutic potential of
      bypassing lymphatic endothelial cell-induced tolerance to enhance cancer
      immunotherapy is discussed.

PMID- 25580370
TI  - Corneal Lymphatics: Role in Ocular Inflammation as Inducer and Responder of
      Adaptive Immunity.
AB  - The normal cornea is devoid of lymphatic and blood vessels, thus suppressing both
      the afferent (lymphatic) and efferent (vascular) arms of the immune response
      contributing to its 'immune privilege'. Inflammation, however, negates this
      unique 'immune' and 'angiogenic' privilege of the cornea. Abnormal blood vessel
      growth from pre-existing limbal vessels into the cornea has been studied for many
      years, but it is only recently that the significance of new lymphatic vessels
      (lymphangiogenesis) in ocular inflammatory diseases has been demonstrated.
      Whereas blood vessels in inflamed ocular surface provide a route of entry for
      immune effector cells to the cornea, lymphatics facilitate the exit of antigen
      presenting cells and antigenic material from the cornea to regional lymph nodes,
      thus promoting induction of adaptive immune response. This review summarizes the
      current evidence for lymphangiogenesis in the cornea, and describes its molecular
      mediators; and discusses the interface between corneal lymphangiogenesis and
      adaptive immunity. Furthermore, the pathophysiologic implications of corneal
      lymphangiogenesis in the setting of allo- and autoimmune-mediated corneal
      inflammation are discussed.

PMID- 25580372
TI  - Functionalizable Amine-based Polymer Nanoparticles.
AB  - Surface functionalization of nanoparticles and host-guest properties of
      nanoassemblies are two critical features in the utilization of nanostructures in
      a variety of applications in materials, chemical, and biological nanotechnology.
      However, simultaneously incorporating these two features in one nanoparticle
      design is a rather challenging task. We have developed a simple and versatile
      nanoparticle platform that addresses this challenge. We have designed and
      characterized a polymer nanoparticle that provides the ability to encapsulate
      hydrophobic guest molecules and surface functionalization with a wide range of
      functional groups. In addition, we have also demonstrated a new and simple
      approach to tune the size of the nanoparticles.

PMID- 25580374
TI  - Comparing epidural analgesia and ON-Q infiltrating catheters for pain management
      after hepatic resection.
AB  - BACKGROUND AND OBJECTIVES: Pain control after hepatic resection presents unique
      challenges as subcostal incisions, rib retraction, and diaphragmatic irritation
      can lead to significant pain. Both epidural analgesia and ON-Q catheters have
      been used for postoperative pain management after hepatic surgery, but to our
      knowledge have not been directly compared. METHODS: The records of 143 patient
      between the ages 18 and 70 were reviewed who underwent hepatic resection by a
      single surgeon. Patients were categorized according to method of postoperative
      pain control. Average pain scores for both study groups were collected until
      POD#3. RESULTS: Demographic data and the length of surgery were similar between
      the groups (all p>0.05). On the day of surgery and POD#1, average pain scores for
      the epidural group were lower than the ON-Q group (P<0.0001 and P=0.0008
      respectively). There was no difference in pain scores on POD #2 (P=.2369) or POD
      #3 (P=0.2289). CONCLUSIONS: Epidural analgesia provides superior pain control on
      the day of surgery and POD#1 when compared to On-Q catheter with IV PCA. There
      was no difference in pain scores on POD#2 or POD#3. Future prospective randomized
      trials comparing these analgesic methods will be required to further evaluate
      enhanced recovery after hepatic surgery.

PMID- 25580375
TI  - Local Health Department Collaborative Capacity to Improve Population Health.
AB  - Local health departments (LHDs) can more effectively develop and strengthen
      community health partnerships when leaders focus on building partnership
      collaborative capacity (PCC), including a multisector infrastructure for
      population health improvement. Using the 2008 National Association of County and
      City Health Officials (NACCHO) Profile survey, we constructed an overall measure
      of LHD PCC comprised of the five dimensions: outcomes-based advocacy, vision
      focus balance, systems orientation, infrastructure development, and community
      linkages. We conducted a series of regression analyses to examine the extent to
      which LHD characteristics and contextual factors were related to PCC. The most
      developed PCC dimension was vision-focus balance, while infrastructure
      development and community linkages were the least developed. In multivariate
      analyses, LHDs that were locally governed (rather than governed by the state),
      LHDs without local boards of health, and LHDs providing a wider range of clinical
      services had greater overall PCC. LHDs serving counties with higher uninsurance
      rates had lower overall PCC. LHDs with lower per capita expenditures had less
      developed partnership infrastructure. LHD discontinuation of clinical services
      may result in an erosion of collaborative capacity unless LHD partnerships also
      shift their foci from services delivery to population health improvement.

PMID- 25580376
TI  - Drug-free macromolecular therapeutics induce apoptosis of patient chronic
      lymphocytic leukemia cells.
AB  - A new drug-free nanotherapeutic approach for B-cell malignancies was developed.
      Exposure of B-cells to an anti-CD20 Fab'-morpholino oligonucleotide1 (MORF1)
      conjugate decorated the cell surface with MORF1; further exposure of the
      decorated cells to multivalent polymer-oligonucleotide2 conjugates (P-MORF2)
      resulted in CD20 clustering at the cell surface with induction of apoptosis. We
      evaluated this concept in chronic lymphocytic leukemia (CLL) cells isolated from
      10 patients. Apoptosis and cytotoxicity were observed in eight samples, including
      2 samples with the 17p13 deletion, which suggested a p53-independent mechanism of
      apoptosis induction. When compared to an anti-CD20 monoclonal antibody (mAb), the
      nanotherapeutic showed significantly more potent apoptosis-inducing activity and
      cytotoxicity. This was due to the multivalency effect (8 binding sites per
      polymer chain) of our design in comparison to the divalent mAb. In conclusion, we
      have developed a novel and potent therapeutic system against CLL and other B-cell
      malignancies with significant advantages over conventional chemo-immunotherapy. 

PMID- 25580373
TI  - Genetic Epidemiology of Psoriasis.
AB  - Psoriasis is a chronic, inflammatory, immune-mediated skin condition with a
      prevalence of 0-11.8% across the world. It is associated with a number of
      cardiovascular, metabolic, and autoimmune disease co-morbidities. Psoriasis is a
      multifactorial disorder, influenced by both genetic and environmental factors.
      Its genetic basis has long been established through twin studies and familial
      clustering. The association of psoriasis with the HLA-Cw6 allele has been shown
      in many studies. Recent genome-wide association studies have identified a large
      number of other genes associated with psoriasis. Many of these genes regulate the
      innate and adaptive immune system. These findings indicate that a dysregulated
      immune system may play a major role in the pathogenesis of psoriasis. In this
      article, we review the clinical and genetic epidemiology of psoriasis with a
      brief description of the pathogenesis of disease.

PMID- 25580377
TI  - Mediation Analysis with Multiple Mediators.
AB  - Recent advances in the causal inference literature on mediation have extended
      traditional approaches to direct and indirect effects to settings that allow for
      interactions and non-linearities. In this paper, these approaches from causal
      inference are further extended to settings in which multiple mediators may be of
      interest. Two analytic approaches, one based on regression and one based on
      weighting are proposed to estimate the effect mediated through multiple mediators
      and the effects through other pathways. The approaches proposed here accommodate
      exposure-mediator interactions and, to a certain extent, mediator-mediator
      interactions as well. The methods handle binary or continuous mediators and
      binary, continuous or count outcomes. When the mediators affect one another, the
      strategy of trying to assess direct and indirect effects one mediator at a time
      will in general fail; the approach given in this paper can still be used. A
      characterization is moreover given as to when the sum of the mediated effects for
      multiple mediators considered separately will be equal to the mediated effect of
      all of the mediators considered jointly. The approach proposed in this paper is
      robust to unmeasured common causes of two or more mediators.

PMID- 25580378
TI  - Transforaminal lumbar interbody fusion rates in patients using a novel titanium
      implant and demineralized cancellous allograft bone sponge.
AB  - BACKGROUND: Transforaminal lumbar interbody fusion (TLIF) with grafting and
      implant options like iliac crest bone graft (ICBG), recombinant bone
      morphogenetic protein (rhBMP), and polyetheretherketone (PEEK) cages have been
      reported to achieve extremely high fusion rates. Unfortunately, these options
      have also been frequently cited in the literature as causing postoperative
      morbidity and complications at a high cost. Knowing this, we sought to
      investigate TLIF using an acid-etched, roughened titanium cage that upregulates
      osteogenesis to see if similar fusion rates to those cited for ICBG, rhBMP, and
      PEEK cages could be safely achieved with minimal morbidity and complications.
      MATERIALS AND METHODS: A radiographic fusion study of 82 patients who underwent
      TLIF using an acid-etched, roughened titanium cage with demineralized cancellous
      bone graft was conducted. Fusion was assessed and graded by an independent
      radiologist using computed tomography scan with sagittal and coronal
      reconstructions. RESULTS: Fusion rates at 6 months were 41 of 44 (93.2%) and at
      12 months were 37 of 38 (97.4%). There were no radiographic device-related
      complications. CONCLUSIONS: TLIF with an acid-etched, roughened titanium cage
      filled with a decalcified bone graft achieved similar fusion rates to historical
      controls using ICBG, rhBMP, and PEEK.

PMID- 25580379
TI  - Trypanosome Transmission Dynamics in Tsetse.
AB  - Tsetse flies (Diptera:Glossinidae) are vectors of African trypanosomes. Tsetse
      undergo viviparous reproductive biology, and depend on their obligate
      endosymbiont (genus Wigglesworthia) for the maintenance of fecundity and immune
      system development. Trypanosomes establish infections in the midgut and salivary
      glands of the fly. Tsetse's resistance to trypanosome infection increases as a
      function of age. Among the factors that mediate resistance to parasites are
      antimicrobial peptides (AMPs) produced by the Immune deficiency (Imd) signaling
      pathway, peptidoglycan recognition protein (PGRP) LB, tsetse-EP protein and the
      integrity of the midgut peritrophic matrix (PM) barrier. The presence of obligate
      Wigglesworthia during larval development is essential for adult immune system
      maturation and PM development. Thus, Wigglesworthia prominently influences the
      vector competency of it's tsetse host.

PMID- 25580380
TI  - Vitamin D Deficiency in Pediatric Critical Illness.
AB  - INTRODUCTION: The potential role for vitamin D in infection has been well
      described in adults. The objective of our study was to determine the prevalence
      of vitamin D insufficiency and to evaluate the relationship between vitamin D
      status and markers of innate immunity and infection in critically ill children.
      HYPOTHESIS: Vitamin D deficiency was highly prevalent in children with critical
      illness and correlated with the severity of illness and dysfunction in innate
      immunity. METHODS: We performed a prospective clinical observational study with
      both case and control groups in the pediatric intensive care unit (PICU). Vitamin
      D status was defined as vitamin D sufficient (25-hydroxyvitamin D (25(OH)D>= 20
      ng/mL), vitamin D insufficient (25(OH)D 10 to 20 ng/mL), and vitamin D deficient
      (25(OH)D <10 ng/mL). Vitamin D status, severity of illness scores, and
      cathelicidin, and other clinical data were collected. RESULTS: Sixty-one PICU
      patients and 46 control patients were enrolled. Over 60% of the PICU cases were
      found to be vitamin D insufficient while less than 1/3 of the controls were
      insufficient (p < 0.0001). No significant correlation was seen between plasma
      25(OH)D and any severity of illness scores. Cases with asthma had a significantly
      lower median level 25(OH)D (16.9 ng/mL) than cases without asthma (18.7 ng/mL).
      Over 50% of patients hospitalized during the fall and winter were considered
      vitamin D deficient or insufficient whereas in the sunnier seasons (spring and
      summer) the prevalence of vitamin D deficiency/insufficiency decreased to about
      30% (p = 0.003). CONCLUSIONS: The overall finding of profound vitamin D
      deficiency in the pediatric critical care population is an important finding.
      Significant seasonal differences were noted even in the critically ill. Certain
      diseases like asthma in critically ill children merit further study.

PMID- 25580381
TI  - RAPID HOME-BASED HIV TESTING TO REDUCE COSTS IN A LARGE TUBERCULOSIS COHORT
      STUDY.
AB  - To reduce costs in a large tuberculosis household contact cohort study in Lima,
      Peru, we replaced laboratory-based HIV testing with home-based rapid testing. We
      developed a protocol and training course to prepare staff for the new strategy;
      these included role playing for home-based deployment of the Determine(r) HIV 1/2
      Ag/Ac Combo HIV test. Though the rapid HIV test produced more false-positives,
      the overall cost per participant tested, refusal rate and time to confirmatory
      HIV testing were lower with the home-based rapid testing strategy compared to the
      original approach. Rapid testing could be used in similar research or routine
      care settings.

PMID- 25580382
TI  - Assessment of stigma associated with tuberculosis in Mexico.
AB  - BACKGROUND: Stigma is a major barrier to health care access and impacts the
      quality of life for individuals affected by tuberculosis (TB). Assessing TB
      stigma is essential to addressing health disparities. However, no such instrument
      was available in Mexico at the time of our study. This study examined the
      adaptability of the TB and human immunodeficiency virus (HIV) stigma scales
      previously used in Thailand. METHODS: The original scale, developed in English,
      was linguistically adapted to Spanish and administered to 217 individuals
      affected by TB in five states in Mexico. The TB-HIV stigma subscales were
      designed to assess individual and community perspectives. Additional data
      collected included general information and socio-demographics. Assessment of
      psychometric properties included basic statistical tests, evaluation of
      Cronbach's alpha and factor analysis. RESULTS: We found no significant
      statistical differences associated with higher stigma scores by location, age,
      marital status, education and stigma scores. Factor analysis did not create any
      new factors. Internal consistency reliability coefficients were satisfactory
      (Cronbach alpha = 0.876-0.912). CONCLUSION: The use of the stigma scales has
      implications for 1) health improvements, 2) research on stigma and health
      disparities, and 3) TB and HIV stigma interventions. Further research is needed
      to examine transferability among larger and randomly selected Spanish-speaking
      populations.

PMID- 25580384
TI  - Study of Insulin Resistance in Subclinical Hypothyroidism.
AB  - BACKGROUND: Thyroid hormones influences glucose homeostasis. The association of
      insulin resistance in overt hypothyroidism is well proven, but very less
      information is available about insulin action on subclinical hypothyroidism.
      OBJECTIVE: This study was done to evaluate the association between thyroid
      hormones and insulin resistance in subclinical hypothyroidism (SCH). MATERIALS
      AND METHODS: Thirty subjects diagnosed as SCH and 30 age matched euthyroids were
      included. Serum TSH, FT3, FT4, fasting plasma glucose and insulin were estimated.
      Homeostasis Model Assessment was used to assess insulin resistance (HOMA- IR).
      RESULTS AND CONCLUSION: Serum TSH levels were significantly increased in SCH
      (14.20 +/- 5.23 MUU/ml) when compared with euthyroids (2.24 +/-1.43MUU/ml; P<
      0.0001). Serum FT3, FT4 levels in SCH (2.96+/-0.80 pg/ml & 1.15 +/- 0.52 ng/dl)
      were within the normal range. The mean insulin levels were significantly elevated
      in SCH (9.07+/-3.41 MUU/ml) when compared with euthyroids (5.28+/- 2.18 MUU/ml; P
      value < 0.0001). The mean HOMA IR was significantly elevated in SCH (2.03 +/-
      0.95) when compared with euthyroids (1.05+/-0.45, P-value < 0.0001). TSH levels
      positively and moderately correlated with insulin (r= 0.43 P=0.03) and HOMA IR (r
      =0.48; P= 0.01). FT3 levels negatively and strongly correlated with insulin (r= 
      0.5, P=0.004) and moderately with HOMA IR (r= -0.38, P= 0.04). FT4 levels
      negatively and weakly correlated with insulin and IR (r= - 0.11, P=0.54; r= -
      0.07, P=0.69 respectively). To conclude, SCH is associated with insulin
      resistance. Hence there is an increased risk of insulin resistance associated
      disorders such as metabolic syndrome, cardiovascular events in SCH.

PMID- 25580383
TI  - Androgen receptor epigenetics.
AB  - The androgen receptor (AR) is a transcription factor that drives the
      differentiation of prostate epithelium by regulating the expression of several
      hundred genes. Conversely, AR also plays a central role in prostate cancer (PCa)
      development, and it continues to be active in tumors that relapse after
      castration (castration-resistant prostate cancer, CRPC). The transactivation
      function of AR has been extensively studied, and AR can also function as a
      transcriptional repressor on a distinct set of genes, but the identity of the AR
      regulated genes that are critical for PCa remain unclear. Moreover, the extent to
      which AR acquires new functions during PCa development and progression remains to
      be determined. Recent studies have highlighted the central role of chromatin
      structure and histone posttranslational modifications in determining the spectrum
      of genes regulated by AR and all other transcription factors. While the role of
      DNA methylation in the epigenetic regulation of gene expression is well
      established, it is now appreciated that chromatin structure plays a central and
      dynamic role in the epigenetic regulation of gene expression. The focus of this
      review is on AR interactions with chromatin and how they regulate AR function in
      PCa development and progression.

PMID- 25580385
TI  - CTTTA Deletion/Insertion polymorphism in 3'-UTR of LEPR gene in type 2 diabetes
      subjects belonging to Kashmiri population.
AB  - BACKGROUND: Type 2 diabetes mellitus is a multi-factorial disease in which both
      genetic and non-genetic factors interact in order to precipitate the diabetic
      phenotype. Among various predisposing genetic loci, a pentanucleotide (CTTTA)
      Del/Ins variant in the 3'-UTR of the LEPR gene is associated with type 2 diabetes
      and its related traits. This study was done to explicate for the first time the
      association of this Del/Ins polymorphism of LEPR gene in type 2 diabetes patients
      belonging to the ethnic population of Kashmir valley. METHODS: 670 unrelated
      subjects comprising of 320 type 2 diabetes patients and 350 healthy controls were
      included in the study. Genotyping of the untranslated region of LEPR gene
      encompassing this Del/Ins variant was done by PCR-RFLP technique and results were
      validated by direct sequencing. RESULTS: Genotype frequencies for both type 2
      diabetes cases and healthy controls were consistent with Hardy-Weinberg
      equilibrium (chi(2) = 3.09 and 2.37, P = NS). The Del/Del genotype was
      predominantly found in cases than controls (P = 0.003, OR: 0.62, CI: 0.45-0.85).
      Carriers of Ins/Ins genotype were relatively protected against the risk factors
      (P = 0.0004, OR: 0.31, 95% CI: 0.15-0.61). A positive association was observed
      between the Del allele and the risk factors of type 2 diabetes. CONCLUSION: The
      results elucidate that the CTTTA Del allele is a genotypic risk factor of type 2
      diabetes in the Kashmiri population.

PMID- 25580387
TI  - Sensitivity analysis for direct and indirect effects in the presence of exposure
      induced mediator-outcome confounders.
AB  - Questions of mediation are often of interest in reasoning about mechanisms, and
      methods have been developed to address these questions. However, these methods
      make strong assumptions about the absence of confounding. Even if exposure is
      randomized, there may be mediator-outcome confounding variables. Inference about
      direct and indirect effects is particularly challenging if these mediator-outcome
      confounders are affected by the exposure because in this case these effects are
      not identified irrespective of whether data is available on these exposure
      induced mediator-outcome confounders. In this paper, we provide a sensitivity
      analysis technique for natural direct and indirect effects that is applicable
      even if there are mediator-outcome confounders affected by the exposure. We give
      techniques for both the difference and risk ratio scales and compare the
      technique to other possible approaches.

PMID- 25580386
TI  - THE CONSUMPTION OF RED PUPUNHA (BACTRIS GASIPAES KUNTH) INCREASES HDL CHOLESTEROL
      AND REDUCES WEIGHT GAIN OF LACTATING AND POST-LACTATING WISTAR RATS.
AB  - INTRODUCTION: The lactating and post-lactating periods are marked by large
      metabolic change. Production of milk is 60% lipid dependent. We reported in a
      recent scientific meeting that Red pupunha palm tree fruit increases HDL
      cholesterol in lactating rats. This study evaluated if consumption of Red Pupunha
      by adult female rats has a beneficial impact on the lipid metabolism of lacting
      and post-lacting adult rats. OBJECTIVE: Evaluate if consumption of red pupunha
      has a beneficial effect in the lipid metabolism of lacting and post-lacting adult
      Wistar rats. RESEARCH METHODS: Four groups including two for control; (1) control
      adult lactating rats, (2) control adults post-lactating rats; and two
      experimental groups; (3) pupunha adults lactating rats and (4) pupunha adult post
      lactating rats were evaluated and compared regarding: weight gain, food
      consumption, plasma total protein, glucose, total lipid, triglycerides, total
      cholesterol and HDL-cholesterol levels. The mean difference and its 95%
      confidence intervals were used for group comparisons. Group comparisons were
      evaluated by using analysis of variance (one-way ANOVA). The statistical
      significance of the pairwise differences among groups was assessed by using the
      two-sided Tukey test. RESULTS: There were no important differences in food
      consumption, plasma glucose, total lipids and triglycerides among groups. The red
      pupunha lactating group gain less weight showing lower body mass index (BMI) than
      controls (p < 0.05). Total cholesterol was lower in red pupunha lactating than in
      controls but not in the red pupunha post-lactating group as compared to controls.
      Triglycerides were lower in the post-lactating red pupunha group as compared to
      the control group (p = 0.039) but not for the lactating groups. Red pupunha
      lactating and post-lactating groups had higher HDL-cholesterol than their
      corresponding control groups (p <= 0.01). CONCLUSION: Original findings include
      the beneficial effect of red pupunha in post-lactating rats increasing the HDL
      cholesterol and lowering the BMI. Red pupunha was confirmed to increase HDL
      cholesterol in lactating rats. These results suggest that red pupunha is a
      healthy fruit to be consumed during lactating and post-lactating periods as it is
      related to better lipid profile and less body weight gain.

PMID- 25580389
TI  - Anti-Inflammatory Activity of the Solvent-Partitioned Fractions from Spergularia
      marina in LPS-Stimulated RAW 264.7 Cells.
AB  - As a part of ongoing research to elucidate and characterize antioxidant and anti
      inflammatory nutraceuticals, solvent-partitioned fractions from Spergularia
      marina were tested for their ability to scavenge radicals and suppress
      inflammation. The results of the 2',7'-dichlorofluorescein diacetate assay
      indicate that solvent-partitioned fractions from S. marina scavenged
      intracellular radicals in H2O2-stimulated mouse macrophages. The tested fractions
      decreased the generation of nitric oxide (NO) and the expression of inflammation
      mediators, namely, inducible nitric oxide synthase (iNOS) and interleukin (IL)-6,
      by lipopolysaccharide (LPS)-induced mouse macrophages, indicating that S. marina
      decreases inflammation. Among all tested fractions [i.e., H2O, n-buthanol (n
      BuOH), 85% aqueous methanol (aq. MeOH), and n-hexane], the 85% aq. MeOH fraction
      showed the strongest antioxidant and anti-inflammatory response. The 85% aq. MeOH
      fraction scavenged 80% of the free radicals produced by H2O2-induced control
      cells. In addition, NO production was 98% lower in 85% aq. MeOH fraction-treated
      cells compared to LPS-induced control cells. The mRNA expression of iNOS and IL-6
      was also suppressed in 85% aq. MeOH fraction-treated cells. The results of the
      current study suggest that the phenolic compound components of S. marina are
      responsible for its antioxidant and anti-inflammatory effects. 

PMID- 25580390
TI  - Effects of benzyl isothiocyanate and its N-acetylcysteine conjugate on induction
      of detoxification enzymes in hepa1c1c7 mouse hepatoma cells.
AB  - The induction of detoxification enzymes by benzyl isothiocyanate (BITC) and its
      synthetic N-acetyl-L-cysteine (NAC) conjugate (NAC-BITC) was examined in
      Hepa1c1c7 murine hepatoma cells. BITC and NAC-BITC inhibited Hepa1c1c7 cell
      growth in a dose-dependent manner. Cell growth was 4.5~57.2% lower in Hepa1c1c7
      cells treated with 0.1~10 MUM BITC than in control-treated Hepa1c1c7 cells. The
      NAC-BITC treatment had a similar inhibitory pattern on Hepa1c1c7 cell growth; 0.5
      MUM and 10 MUM NAC-BITC decreased cell growth by 13.6% and 47.4%, respectively.
      Treatment of Hepa1c1c7 cells with 0.1~2.0 MUM BITC also elicited a dose-response
      effect on the induction of quinone reductase quinone reductase (QR) activity and
      QR mRNA expression. Treatment with 1 MUM and 2 MUM BITC caused 1.8- and 2.8-fold
      inductions of QR mRNA, respectively. By comparison, treatment with 1 MUM and 2
      MUM NAC-BITC caused 1.6- and 1.9-fold inductions of QR mRNA, respectively.
      Cytochrome P450 (CYP) 1A1 and CYP2E1 induction were lower in 0.1~2 MUM BITC
      treated cells than in control-treated cells. CYP2E1 activity was 1.2-fold greater
      in 0.1 MUM NAC-BITC-treated cells than in control-treated cells. However, the
      CYP2E1 activity of cells treated with higher concentrations (i.e., 1~2 MUM) of
      NAC-BITC was similar to the activity of control-treated cells. Considering the
      potential of isothiocyanatesto prevent cancer, these results provide support for
      the use of BITC and NAC-BITC conjugates as chemopreventive agents. 

PMID- 25580391
TI  - Antioxidant and ACE Inhibitory Activity of Cultivated and Wild Angelica gigas
      Nakai Extracts Prepared Using Different Extraction Conditions.
AB  - The purpose of this study was to investigate the biological activities of
      cultivated Angelica gigas Nakai (CAG) and wild Angelica gigas Nakai (WAG)
      extracts prepared by extraction with water, 30% ethanol, 60% ethanol, or 90%
      ethanol. The electron donating ability of the WAG extracts was higher than that
      of the CAG extracts and 0.1% and 1.0% solutions of the comparative substance, L
      ascorbic acid. The superoxide dismutase-like activity of the CAG extracts was
      higher than that of WAG extracts. Superoxide dismutase-like activity was highest
      (33.95%) in the CAG water extract. The total polyphenol content was highest in
      the 60% ethanol extracts of WAG. The nitrite scavenging ability of the CAG and
      WAG extracts was highest at a pH of 1.2. The tyrosinase inhibitory effect was
      highest (43.72%) in the water extract of WAG. The angiotensin converting enzyme
      inhibitory activity was highest (83.84%) in the 60% ethanol extract of WAG. The
      results of the present study will be useful for understanding the antioxidant and
      angiotensin-converting enzyme inhibitory activities of Angelica gigas Nakai
      extracts. 

PMID- 25580388
TI  - Contemporary issues surrounding folic Acid fortification initiatives.
AB  - The impact of folate on health and disease, particularly pregnancy complications
      and congenital malformations, has been extensively studied. Mandatory folic acid
      fortification therefore has been implemented in multiple countries, resulting in
      a reduction in the occurrence of neural tube defects. However, emerging evidence
      suggests increased folate intake may also be associated with unexpected adverse
      effects. This literature review focuses on contemporary issues of concern, and
      possible underlying mechanisms as well as giving consideration the future
      direction of mandatory folic acid fortification. Folate fortification has been
      associated with the presence of unmetabolized folic acid (PteGlu) in blood,
      masking of vitamin B12 deficiency, increased dosage for anti-cancer medication,
      photo-catalysis of PteGlu leading to potential genotoxicity, and a role in the
      pathoaetiology of colorectal cancer. Increased folate intake has also been
      associated with twin birth and insulin resistance in offspring, and altered
      epigenetic mechanisms of inheritance. Although limited data exists to elucidate
      potential mechanisms underlying these issues, elevated blood folate level due to
      the excess use of PteGlu without consideration of an individual's specific
      phenotypic traits (e.g. genetic background and undiagnosed disease) may be
      relevant. Additionally, the accumulation of unmetabolized PteGlu may lead to
      inhibition of dihydrofolate reductase and other enzymes. Concerns
      notwithstanding, folic acid fortification has achieved enormous advances in
      public health. It therefore seems prudent to target and carefully monitor high
      risk groups, and to conduct well focused further research to better understand
      and to minimize any risk of mandatory folic acid fortification. 

PMID- 25580392
TI  - Anti-Diabetic and Anti-Inflammatory Effects of Green and Red Kohlrabi Cultivars
      (Brassica oleracea var. gongylodes).
AB  - The aim of the present study was to evaluate the anti-diabetic, anti
      inflammatory, antioxidant potential, and total phenolic content (TPC) of green
      and red kohlrabi cultivars. Anti-diabetic and anti-inflammatory activities were
      evaluated via protein tyrosine phosphatase (PTP1B) and rat lens aldose reductase
      inhibitory assays and cell-based lipopolysaccharide (LPS)-induced nitric oxide
      (NO) inhibitory assays in RAW 264.7 murine macrophages. In addition, scavenging
      assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical, and
      peroxynitrite (ONOO(-)) were used to evaluate antioxidant potential and TPC was
      selected to assess phytochemical characteristics. Between the two kohlrabi
      cultivars, red kohlrabi (RK) had two times more TPC than green kohlrabi (GK) and
      showed significant antioxidant effects in DPPH, ABTS, and ONOO(-) scavenging
      assays. Likewise, methanol (MeOH) extracts of RK and GK inhibited LPS-induced NO
      production in a dose dependent manner that was further clarified by suppression
      of iNOS and COX-2 protein production. The MeOH extracts of RK and GK exhibited
      potent inhibitory activities against PTP1B with the corresponding IC50 values of
      207+/-3.48 and 287+/-3.22 MUg/mL, respectively. Interestingly, the RK MeOH
      extract exhibited significantly stronger anti-inflammatory, anti-diabetic, and
      antioxidant effects than that of GK MeOH extract. As a result, our study
      establishes that RK extract with a higher TPC might be useful as a potent anti
      diabetic, antioxidant, and anti-inflammatory agent. 

PMID- 25580393
TI  - Antioxidant activity of orange flesh and peel extracted with various solvents.
AB  - The aim of this study was to investigate the antioxidant activity of orange
      (Citrus auranthium) flesh (OF) and peel (OP) extracted with acetone, ethanol, and
      methanol. Antioxidant potential was examined by measuring total phenolic content
      (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (RSA),
      total radical-trapping anti-oxidant potential (TRAP), oxygen radical absorbance
      capacity (ORAC), and cellular antioxidant activity (CAA). The comet assay was
      used to determine the protective effects of OF and OP against H2O2-induced DNA
      damage. TPC was highest in the acetone extracts of OF and OP. DPPH RSA was also
      higher in the acetone extracts than in the ethanol extracts. The DPPH RSA was
      highest in the acetone extracts of OF. The TRAP and ORAC values of the all
      extracts increased in a dose-dependent manner. In the TRAP assay, the acetone
      extracts of OF and OP had the lowest IC50 values. In the CAA assay, the methanol
      and acetone extracts of OP had the lowest IC50 values. All of the samples
      protected against H2O2-induced DNA damage in human leukocytes, as measured by the
      comet assay, but the acetone extracts of OP had the strongest effect. These
      results suggest that acetone is the best solvent for the extraction of
      antioxidant compounds from OF and OP. Furthermore, the high antioxidant activity
      of OP, which is a by-product of orange processing, suggests that it can be used
      in nutraceutical and functional foods. 

PMID- 25580394
TI  - Hesperetin Inhibits Vascular Formation by Suppressing of the PI3K/AKT, ERK, and
      p38 MAPK Signaling Pathways.
AB  - Hesperetin has been shown to possess a potential anti-angiogenic effect,
      including vascular formation by endothelial cells. However, the mechanisms
      underlying the potential anti-angiogenic activity of hesperetin are not fully
      understood. In the present study, we evaluated whether hesperetin has anti
      angiogenic effects in human umbilical vascular endothelial cells (HUVECs). HUVECs
      were treated with 50 ng/mL vascular endothelial growth factor (VEGF) to induce
      proliferation as well as vascular formation, followed by treatment with several
      doses of hesperetin (25, 50, and 100 MUM) for 24 h. Cell proliferation and
      vascular formation were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide and tube formation assay, respectively. In addition,
      cell signaling related to cell proliferation and vascular formation was analyzed
      by western blot. Furthermore, a mouse aorta ring assay was performed to confirm
      the effect of hesperetin on vascular formation. Hesperetin treatment did not
      cause differences in HUVECs proliferation. However, hesperetin significantly
      inhibited VEGF-induced cell migration and tube formation of HUVECs (P<0.05).
      Moreover, hesperetin suppressed the expression of ERK, p38 MAPK, and PI3K/AKT in
      the VEGF-induced HUVECs. In an ex vivo model, hesperetin also suppressed
      microvessel sprouting of mouse aortic rings. Taken together, the findings suggest
      that hesperetin inhibited vascular formation by endothelial cells via the
      inhibition of the PI3K/AKT, ERK and p38 MAPK signaling. 

PMID- 25580396
TI  - Headspace volatile compounds of steamed liriopis tuber tea affected by steaming
      frequency.
AB  - Flavor quality of Liriopis tuber tea that was made using a steaming process was
      studied by measuring changes in headspace volatile compounds. Headspace volatile
      compounds of the prepared samples were isolated, separated and identified by the
      combined system of purge & trap, automatic thermal desorber, gas chromatography,
      and mass selective detector. As steaming frequencies were increased, the area
      percent of aldehydes decreased from 32.01% to 3.39% at 1 and 9 steaming frequency
      times, respectively. However, furans and ketones increased from 18.67% to 33.86%
      and from 9.60% to 17.40% at 1 and 9 times, respectively. The savory flavor of
      Liriopis tuber tea was due to a decrease in aldehydes contributing a fresh flavor
      at the 1st steaming process and newly generated furans from nonenzymatic browning
      with repeated steaming frequencies. These results will provide basic information
      for quality control of the newly developed Liriopis tuber tea. 

PMID- 25580395
TI  - Structural Effects of Sulfated-Glycoproteins from Stichopus japonicus on the
      Nitric Oxide Secretion Ability of RAW 264.7 Cells.
AB  - The effect of various levels of proteins, sulfates, and molecular weight (M w) of
      a sulfated-glycoprotein (NF3) from a sea cucumber, Stichopus japonicus, on nitric
      oxide (NO) releasing capacity from RAW 264.7 cells was investigated. The NF3
      derivatives had various amounts of proteins (4.8~11.2%) and sulfates (6.8~25.2%)
      as well as different M w (640.3*10(3)~109.2*10(3) g/mol). NF3 was able to
      stimulate RAW 264.7 cells to release NO with lower protein contents, indicating
      that the protein moiety was not an important factor to stimulate macrophages. On
      the other hand, the NO inducing capacity was significantly reduced with decreased
      levels of sulfates and M w, implying that sulfates and M w played a pivotal role
      in activating RAW 264.7 cells. It was not clear why sulfates and a certain range
      of M w were essential for stimulating macrophages. It appeared that certain
      levels of sulfates and M w of sulfated-glycoproteins were required to bind to the
      surface receptors on RAW 264.7 cells. 

PMID- 25580397
TI  - Analysis and distribution of esculetin in plasma and tissues of rats after oral
      administration.
AB  - In this study, we developed a method to quantify esculetin (6,7
      dihydroxycoumarin) in plasma and tissues using HPLC coupled with ultraviolet
      detection and measured the level of esculetin in rat plasma after oral
      administration. The calibration curve for esculetin was linear in the range of
      4.8 ng/mL to 476.2 ng/mL, with a correlation coefficient (r(2)) of 0.996, a limit
      of detection value of 33.2 ng/mL, and a limit of quantification value of 100.6
      ng/mL. Recovery rates for the 95.2 ng/mL and 190.5 ng/mL samples were 95.2% and
      100.3%, within-runs and 104.8% and 101.0% between-runs, respectively. The
      relative standard deviation was less than 7% for both runs. In the
      pharmacokinetic analysis, the peak plasma esculetin level was reached 5 min after
      administration (Cmax=173.3 ng/mL; T1/2=45 min; AUC0 ~180 min=5,167.5 ng .
      min/mL). At 180 min post-administration (i.e., after euthanasia), esculetin was
      only detectable in the liver (30.87+/-11.33 ng/g) and the kidney (20.29+/-7.02
      ng/g). 

PMID- 25580398
TI  - Improvement of surface functionalities, including allergenicity attenuation, of
      whole buckwheat protein fraction by maillard-type glycation with dextran.
AB  - The purpose of the current study was to determine the effects of the introduction
      of polysaccharide chains onto the molecular surface of buckwheat proteins on
      buckwheat protein surface functionality. The whole buckwheat protein fraction
      (WBP) was prepared using 50 mM phosphate buffer (pH 7.5) containing 0.5 M NaCl
      and covalently linked with 6 kDa, 17.5 kDa, 40 kDa, 70 kDa, or 200 kDa dextran by
      Maillard-type glycation through controlled dry-heating at 60 degrees C and 79%
      relative humidity for two weeks. Conjugation with 40 kDa dextran improved the
      water solubility and emulsifying properties of WBP without causing a serious loss
      of available lysine; 84.9% of the free amino groups were conserved. In addition,
      we found that the introduction of dextran chains onto the molecular surfaces of
      WBP attenuated the antigenicity of WBP. 

PMID- 25580399
TI  - Relationship between Blood Mercury Level and Risk of Cardiovascular Diseases:
      Results from the Fourth Korea National Health and Nutrition Examination Survey
      (KNHANES IV) 2008-2009.
AB  - Limited epidemiologic data is available regarding the cardiovascular effects of
      mercury exposure. The purpose of this study was to determine the relationship
      between mercury exposure from fish consumption and cardiovascular disease in a
      nationally representative sample of Korean adults using the Fourth Korea National
      Health and Nutrition Examination Survey (KNHANES IV 2008~2009). Survey logistic
      regression models accounting for the complex sampling were used to estimate the
      odds ratios (OR) adjusted for fish consumption frequency, age, education,
      individual annual income, household annual income, body mass index (BMI), waist
      circumference (WC), alcohol consumption status, and smoking status. The mean
      blood mercury level in the population was 5.44 MUg/L. Trends toward increased
      blood mercury levels were seen for increased education level (P=0.0011), BMI
      (P<0.0001), WC (P<0.0001), and fish (i.e., anchovy) consumption frequency
      (P=0.0007). The unadjusted OR for hypertension in the highest blood mercury
      quartile was 1.450 [95% confidential interval (CI): 1.106~1.901] times higher
      than that of the lowest quartile. The fish consumption-adjusted OR for
      hypertension in the highest blood mercury quartile was 1.550 (95% CI:
      1.131~2.123) times higher than that of the lowest quartile, and the OR for
      myocardial infarction or angina in the highest blood mercury quartile was 3.334
      (95% CI: 1.338~8.308) times higher than that of the lowest quartile. No
      associations were observed between blood mercury levels and stroke. These
      findings suggest that mercury in the blood may be associated with an increased
      risk of hypertension and myocardial infarction or angina in the general Korean
      population. 

PMID- 25580400
TI  - Vaccinium uliginosum L. Improves Amyloid beta Protein-Induced Learning and Memory
      Impairment in Alzheimer's Disease in Mice.
AB  - The present study investigated the effects of Vaccinium uliginosum L. (bilberry)
      on the learning and memory impairments induced by amyloid-beta protein (AbetaP) 1
      42. ICR Swiss mice were divided into 4 groups: the control (Abeta40-1A), control
      with 5% bilberry group (Abeta40-1B), amyloid beta protein 1-42 treated group
      (Abeta1-42A), and Abeta1-42 with 5% bilberry group (Abeta1-42B). The control was
      treated with amyloid beta-protein 40-1 for placebo effect, and Alzheimer's
      disease (AD) group was treated with amyloid beta-protein 1-42. Amyloid beta
      protein 1-42 was intracerebroventricular (ICV) micro injected into the
      hippocampus in 35% acetonitrile and 0.1% trifluoroacetic acid. Although bilberry
      added groups tended to decrease the finding time of hidden platform, no
      statistical significance was found. On the other hand, escape latencies of AbetaP
      injected mice were extended compared to that of Abeta40-1. In the Probe test,
      bilberry added Abeta1-42B group showed a significant (P<0.05) increase of probe
      crossing frequency compared to Abeta1-42A. Administration of amyloid protein
      (Abeta1-42) decreased working memory compared to Abeta40-1 control group. In
      passive avoidance test, bilberry significantly (P<0.05) increased the time of
      staying in the lighted area compared to AD control. The results suggest that
      bilberry may help to improve memory and learning capability in chemically induced
      Alzheimer's disease in experimental animal models. 

PMID- 25580401
TI  - Protective Effects of Black Rice Extracts on Oxidative Stress Induced by tert
      Butyl Hydroperoxide in HepG2 Cells.
AB  - Black rice contains many biologically active compounds. The aim of this study was
      to investigate the protective effects of black rice extracts (whole grain
      extract, WGE and rice bran extract, RBE) on tert-butyl hydroperoxide (TBHP)
      induced oxidative injury in HepG2 cells. Cellular reactive oxygen species (ROS),
      antioxidant enzyme activities, malondialdehyde (MDA) and glutathione (GSH)
      concentrations were evaluated as biomarkers of cellular oxidative status. Cells
      pretreated with 50 and 100 MUg/mL of WGE or RBE were more resistant to oxidative
      stress in a dose-dependent manner. The highest WGE and BRE concentrations
      enhanced GSH concentrations and modulated antioxidant enzyme activities
      (glutathione reductase, glutathione-S-transferase, catalase, and superoxide
      dismutase) compared to TBHP-treated cells. Cells treated with RBE showed higher
      protective effect compared to cells treated with WGE against oxidative insult.
      Black rice extracts attenuated oxidative insult by inhibiting cellular ROS and
      MDA increase and by modulating antioxidant enzyme activities in HepG2 cells. 

PMID- 25580402
TI  - Effects of Brown Rice Extract Treated with Lactobacillus sakei Wikim001 on
      Osteoblast Differentiation and Osteoclast Formation.
AB  - Phytic acid (myo-inositol hexakisphosphate) or phytate is considered an anti
      nutrient due to the formation of precipitated complexes that strongly reduces the
      absorption of essential dietary minerals. In this study, brown rice with reduced
      phytate was made by inoculation with Lactobacillus sakei Wikim001 having high
      phytase activity. The effects of brown rice extract treated with L. sakei
      Wikim001 (BR-WK) on osteoblast differentiation and osteoclast formation were
      investigated. The proliferation of SaOS-2 cells was measured by the MTT assay.
      Treatment with BR-WK increased cell proliferation by 136% at a concentration of
      100 MUg/mL. The Alkaline phosphate activity in SaOS-2 cells was 129% higher when
      BR-WK was processed at a concentration of 100 MUg/mL. The proliferation of bone
      marrow macrophages decreased by nearly 60% in response to treatment with BR-WK.
      In addition, BR-WK reduced the number of tartrate-resistant acid phosphatase
      positive (TRAP(+)) multinucleated cells from bone marrow macrophages. These
      results indicate that BR-WK stimulates bone formation through its positive action
      on osteoblast differentiation and function and furthermore, decreases osteoclast
      differentiation. 

PMID- 25580403
TI  - Effect of thickener type on the rheological properties of hot thickened soups
      suitable for elderly people with swallowing difficulty.
AB  - Flow and dynamic rheological properties of hot thickened soups for consumption by
      the elderly people with swallowing difficulty (dysphagia) were investigated at a
      serving temperature of 60 degrees C. In this study, sea mustard soup (SMS) and
      dried pollock soup (DPS), which have been widely known as favorable hot soups
      provided in a domestic hospitals and nursing homes for dysphagic patients, were
      thickened with four commercial xanthan gum (XG)-based food thickeners (coded A~D)
      marketed in Korea. Thickened soups prepared with different thickeners showed high
      shear-thinning flow behaviors (n=0.15~0.21). Apparent viscosity (etaa,50),
      consistency index (K), storage modulus (G'), and loss modulus (G") demonstrated
      differences in rheological behaviors between the XG-based thickeners. The
      magnitudes of G' were much higher than those of G" over the entire range of
      frequency (omega) with the high dependence on omega, showing the rheological
      behavior similar to a weak gel. In general, all rheological parameter values of
      thickened DPS samples were higher when compared to the thickened SMS samples.
      These results indicate that flow and dynamic rheological properties of hot
      thickened soups containing commercial XG-based thickeners are strongly dependent
      on the type of thickener and soup. 

PMID- 25580404
TI  - Zinc Restored the Decreased Vascular Smooth Muscle Cell Viability under
      Atherosclerotic Calcification Conditions.
AB  - Zinc is considered to be involved in maintaining healthy vascular condition.
      Atherosclerotic calcification of vascular smooth muscle cells (VSMCs) occurs via
      the mechanism of cell death; therefore, cell viability is a critical factor for
      preventing VSMC calcification. In this study, we tested whether zinc affected
      VSMC viability under both normal physiological non-calcifying (0 mM P) and
      atherosclerotic calcifying conditions (3 and 5 mM P), since VSMC physiological
      characters change during the VSMC calcification process. The study results showed
      that an optimal zinc level (15 MUM) restored the decreased VSMC viability which
      was induced under low zinc levels (0 and 1 MUM) and calcifying conditions (3 and
      5 mM P) at 9 and 15 days culture. This zinc-protecting effect for VSMC viability
      is more prominent under atherosclerotic calcifying condition (3 and 5 mM P) than
      normal condition (0 mM P). Also, the increased VSMC viability was consistent with
      the decreased Ca and P accumulation in VSMC cell layers. The results suggested
      that zinc could be an effective biomineral for preventing VSMC calcification
      under atherosclerotic calcifying conditions. 

PMID- 25580405
TI  - The combined effect of caffeine and ornithine on the mood of healthy office
      workers.
AB  - Caffeine is widely consumed and well known for stimulating the central nervous
      system. When developing new foods and beverages that contain caffeine, it is
      important to explore the potential synergistic effects of consuming amino acids
      and other food ingredients with caffeine on humans. Given the physiological
      pathways affected by the amino acid ornithine, consumption of ornithine with
      caffeine may have synergistic effects. The purpose of the present study was to
      examine the effect of consuming caffeine with ornithine in humans. The study used
      a randomized, placebo-controlled, double-blinded crossover design. The subjects
      were all healthy office workers who ingested the placebo, 100 mg caffeine, or 100
      mg caffeine plus 200 mg ornithine in the morning and completed questionnaires
      about their mood. Office workers who consumed the combination of caffeine and
      ornithine had higher mood ratings 8 h after consumption than office workers who
      consumed caffeine alone. The results of the present study suggest that there is a
      unique synergistic effect between caffeine and ornithine on the mood of healthy
      office workers and that ornithine may potentiate the effects of caffeine. 

PMID- 25580406
TI  - Heat-induced coarsening of layer-by-layer assembled mixed Au and Pd
      nanoparticles.
AB  - This article shows the coarsening behavior of nanoparticle multilayers during
      heat treatments which produce larger metallic nanostructures with varying shapes
      and sizes on glass slides. Nanoparticle multilayer films are initially
      constructed via the layer-by-layer self-assembly of small and monodispersed gold
      and/or palladium nanoparticles with different compositions (gold only, palladium
      only, or both gold and palladium) and assembly orders (compounding layers of gold
      layers over palladium layers or vice versa). Upon heating the slides at 600
      degrees C, the surface nanoparticles undergo coalescence becoming larger
      nanostructured metallic films. UV-Vis results show a clear reliance of the
      layering sequence on the optical properties of these metal films, which
      demonstrates an importance of the outmost (top) layers in each nanoparticle
      multilayer films. Topographic surface features show that the heat treatments of
      nanoparticle multilayer films result in the nucleation of nanoparticles and the
      formation of metallic cluster structures. The results confirm that different
      composition and layering sequence of nanoparticle multilayer films clearly affect
      the coalescence behavior of nanoparticles during heat treatments.

PMID- 25580407
TI  - Surgical treatment of obstructed left-sided colorectal cancer patients.

PMID- 25580408
TI  - Preoperative staging with positron emission tomography in patients with
      colorectal cancer.

PMID- 25580409
TI  - Intraoperative peritoneal lavage: limitations of current evidence for clinical
      implementation.

PMID- 25580410
TI  - Effect of laparoscopic surgery on the initiation and completion of chemotherapy
      in patients with colon cancer.

PMID- 25580411
TI  - Comparative study of postoperative complications in patients with and without an
      obstruction who had left-sided colorectal cancer and underwent a single-stage
      operation after mechanical bowel preparation.
AB  - PURPOSE: The purpose of this study is to compare postoperative complications for
      single-stage surgery after mechanical bowel preparation in patients who
      experienced obstruction and those who did not. METHODS: From 2000 to 2011, 1,224
      patients underwent a single-stage operation for left colorectal cancer after
      bowel preparation. Nonobstruction (NOB) and obstruction (OB) colorectal cancer
      patients were 1,053 (86.0%) and 171 (14.0%), respectively. Postoperative
      morbidity and mortality were compared between groups. RESULTS: The OB group had
      poor preoperative conditions (age, white blood cell, hemoglobin, albumin level,
      and advanced tumor stage) compared with the NOB group (P < 0.05). Mean on-table
      lavage time for the OB group was 17.5 minutes (range, 14-60 minutes). Mean
      operation time for the OB group was statistically longer than that of the NOB
      group (OB: 210 minutes; range, 120-480 minutes vs. NOB: 180 minutes; range, 60
      420 minutes; P < 0.001). Overall morbidity was similar between groups (NOB: 19.7%
      vs. OB: 23.4%, P = 0.259). Major morbidity was more common in the OB group than
      in the NOB group, but the difference was without significance (OB: 11.7% vs. NOB:
      7.6%, P = 0.070). Postoperative death occurred in 16 patients (1.3%), and death
      in the OB group (n = 7) was significantly higher than it was in the NOB group (n
      = 9) (4.1% vs. 0.9%, P = 0.001). Twelve patients had surgical complications,
      which were the leading cause of postoperative death: postoperative bleeding in
      five patients and leakage in seven patients. CONCLUSION: Postoperative morbidity
      for a single-stage operation for obstructive left colorectal cancer is comparable
      to that for NOB, regardless of poor conditions of the patient.

PMID- 25580412
TI  - Reliability of (18)f-fluorodeoxyglucose positron emission tomography/computed
      tomography in the nodal staging of colorectal cancer patients.
AB  - PURPOSE: Lymph-node metastasis is considered as critical prognostic factor in
      colorectal cancer. A preoperative evaluation of lymph-node metastasis can also
      help to determine the range of distant lymph node dissection. However, the
      reliability of (18)F-fluorodeoxyglucose positron emission tomography/computed
      tomography (FDG-PET/CT) in the detection of lymph-node metastasis is not fully
      known. METHODS: The medical records of 433 patients diagnosed with colorectal
      cancer were reviewed retrospectively. FDG-PET/CT and CT were performed on all
      patients. Lymph nodes were classified into regional and distant lymph nodes
      according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual,
      7th edition. RESULTS: The patients included 231 males (53.3%) and 202 females
      (46.7%), with a mean age of 64.7 +/- 19.0 years. For regional lymph nodes, the
      sensitivity of FDG-PET/CT was lower than that of CT (57.1% vs. 73.5%, P < 0.001).
      For distant lymph nodes, the sensitivity of FDG-PET/CT was higher than that of CT
      (64.7% vs. 52.9%, P = 0.012). The sensitivity of FDG-PET/CT for regional lymph
      nodes was higher in patients with larger primary tumors. The positivity of lymph
      node metastasis for FDG-PET/CT was affected by carcinoembryonic antigen levels,
      tumor location, and cancer stage for regional lymph nodes and by age and cancer
      stage for distant lymph nodes (P < 0.05). CONCLUSION: The sensitivity of FDG
      PET/CT for regional lymph-node metastasis was not superior to that of CT.
      However, FDG-PET/CT provides helpful information for determining surgical plan
      especially in high risk patients group.

PMID- 25580413
TI  - Role of peritoneal lavage cytology and prediction of prognosis and peritoneal
      recurrence after curative surgery for colorectal cancer.
AB  - PURPOSE: In colorectal cancer, the role of detecting free malignant cells from
      peritoneal lavage is currently unclear. In this study, we investigated the
      positive rate of free malignant cells in peritoneal lavage fluid and their
      predictive value for prognosis and peritoneal recurrence after a curative
      resection. METHODS: From October 2009 to December 2011, in a prospective manner,
      we performed cytologic examinations of peritoneal lavage fluid obtained just
      after the abdominal incision from 145 patients who underwent curative surgery for
      colorectal cancer. We used proportional hazard regression models to analyze the
      predictive role of positive cytology for peritoneal recurrence and survival.
      RESULTS: Among total 145 patients, six patients (4.1%) showed positive cytology.
      During the median follow-up of 32 months (range, 8-49 months), 27 patients
      (18.6%) developed recurrence. Among them, 5 patients (3.4%) showed peritoneal
      carcinomatosis. In the multivariate analysis, positive cytology was an
      independent predictive factor for peritoneal recurrence (hazard ratio [HR],
      136.5; 95% confidence interval [CI], 12.2-1,531.9; P < 0.0001) and an independent
      poor prognostic factor for overall survival (HR, 11.4; 95% CI, 1.8-72.0; P =
      0.009) and for disease-free survival (HR, 11.1; 95% CI, 3.4-35.8; P < 0.0001).
      CONCLUSION: Positive cytology of peritoneal fluid was significantly associated
      with peritoneal recurrence and worse survival in patients undergoing curative
      surgery for colorectal cancer. Peritoneal cytology might be a useful tool for
      selecting patients who need intraperitoneal or systemic chemotherapy.

PMID- 25580414
TI  - Comparison of compliance of adjuvant chemotherapy between laparoscopic and open
      surgery in patients with colon cancer.
AB  - PURPOSE: Many studies have shown that the completion of adjuvant chemotherapy
      improves the survival rate. Recently, laparoscopic surgery has been used to treat
      patients with colon cancer. We analyzed the relationship between the completion
      of adjuvant chemotherapy and the operation method. METHODS: We retrospectively
      analyzed the medical records of 147 patients diagnosed with colon cancer from
      January 1, 2009, to May 31, 2012. The numbers of patients who underwent
      laparoscopic and open surgery were 91 and 56, respectively. We analyzed the
      relationship between the operation method and various factors such as the
      completion rate of chemotherapy, the patient's age, gender, and physical
      activity, the postoperative hospital stay, the start time of chemotherapy, and
      the patient's body mass index (BMI), TNM stage, and type of health insurance.
      RESULTS: In the laparoscopic surgery group, the postoperative hospital stay (13.5
      +/- 14.82 days vs. 19.6 +/- 11.38 days, P = 0.001) and start time of chemotherapy
      (17.7 +/- 17.48 days vs. 23.0 +/- 15.00 days, P = 0.044) were shorter, but the
      percent complete of chemotherapy (71/91 [78.0%] vs. 38/56 [67.8%], P = 0.121),
      and survival rate (88/91 [96.7%], 47/56 [83.9%], P = 0.007) were higher than they
      were in the open surgery group. Patients who were elderly, had a low BMI, and a
      high American Society of Anesthesiologists score were less likely to complete
      adjuvant chemotherapy than other patients were. CONCLUSION: Laparoscopic surgery
      shows a shorter postoperative hospital stay, a shorter start time of
      chemotherapy, and a higher survival rate. Laparoscopic surgery may be expected to
      increase compliance of chemotherapy and to improve survival rate.

PMID- 25580415
TI  - Acute peritonitis caused by a fibrosarcoma of the transverse colon in an adult.
AB  - A fibrosarcoma is a malignant mesenchymal tumor derived from fibrous connective
      tissue. It usually develops in the deep soft tissues of the extremities, as well
      as the trunk, head, and neck. In extremely rare cases, a fibrosarcoma may occur
      in the gastrointestinal tract. Most cases of fibrosarcoma in the gastrointestinal
      tract have been observed in the pediatric age group while only a few cases have
      been reported in adults. A 61-year-old male presented with pain in the entire
      abdominal region. Chest radiography showed free air in the subphrenic space.
      After an emergency operation, we found a solid mass around the transverse colon
      and performed a segmental resection with a lymphatic dissection of the transverse
      colon, including the mass. A pathologic examination showed a fibrosarcoma with a
      perforation. There was no perioperative complication. The patient was discharged
      on postoperative day 11 and had follow-ups for 1 year without any recurrence. 

PMID- 25580416
TI  - Proper management for morbid iatrogenic retroperitoneal barium insufflation.
AB  - A barium enema is a diagnostic and therapeutic procedure commonly used for colon
      and rectum problems. Rectal perforation with extensive intra- and/or
      extraperitoneal spillage of barium is a devastating complication of a barium
      enema that leads to a significant increase in patient mortality. Due to the low
      number of reported cases in recent scientific literature and the lack of
      experience with the management of these cases, we would like to present our
      treatment approach to a rare case of retroperitoneal contamination with barium,
      followed by its intraperitoneal involvement during a diagnostic barium enema. Our
      experience with long-term management of the patient and the good outcome will be
      depicted in this paper. 

PMID- 25580417
TI  - Acute hyponatremia with seizure and mental change after oral sodium
      picosulfate/magnesium citrate bowel preparation.
AB  - Sodium picosulfate/magnesium citrate (Picolight Powder), which is used as a bowel
      preparation for the colon and the rectum, can cause a severe electrolyte
      imbalance like hyponatremia. When hyponatremia gets severe or occurs rapidly, it
      can lead to death due to associated complications. We have experienced a case of
      hyponatremia associated with seizure and loss of consciousness in a 76-year-old
      woman, who took sodium picosulfate/magnesium citrate as a bowel preparation for
      colonoscopy. She was taking thiazide and synthroid for the treatment of
      hypertension and hypothyroidism, respectively, and she had other underlying
      medical conditions such as a history of seizure and dementia. Following the
      diagnosis of hyponatremia, we used an intravenous injection of 3% NaCl to
      normalize the sodium level in her serum, and her associated symptoms soon
      disappeared. 

PMID- 25580418
TI  - Effective Anti-aging Strategies in an Era of Super-aging.
AB  - The societies of the world in the 21(st) century have faced challenges arising
      from an aging population as the fertility rate has dropped dramatically and
      medical advances have extended the average human life span. The elderly aged 65
      years or older make up at least 20% of the population in Korea, making the
      country a super-aging society as defined by the United Nations. The number of
      elderly women is higher than that of elderly men and women live longer than men.
      Based on the analysis of recent trends in previous studies, this study aimed to
      suggest practical strategies to utilize isoflavones, substances chemically
      similar to the female hormone estrogen, and to search for effective anti-aging
      strategies using this substance for women to be prepared to reach the elderly
      stage in good health. 

PMID- 25580419
TI  - Pharmacotherapy for obesity.
AB  - Obesity is an important risk factor for metabolic disease and various cancers.
      Treatments of obesity include lifestyle intervention, pharmacotherapy, and
      bariatric surgery. If weight loss with lifestyle intervention is only modest,
      pharmacotherapy might be needed. Pharmacotherapy agents can be grouped by
      treatment period as short term or long term use agent. Several sympathomimetic
      drugs such as benzphetamine, diethylpropion, phendimetrazine and phentermine, are
      approved for short term treatment due to their safety issues. For long term
      treatment, orlistat, lorcaserin, and combination of phentermine/topiramate are
      approved by U.S. Food and Drug Administration (FDA). Orlistat partially blocks
      intestinal digestion of fat, therefore producing weight loss. Lorcaserin is a
      serotonin 2C receptor agonist. The combination of phentermine/topiramate produces
      a mean weight loss of 8-10 kg. Side effects of each drug are quite different. For
      obesity patient, side effects are important factor when choosing drugs. The goal
      of this article is to review currently available anti-obesity drugs. 

PMID- 25580420
TI  - Expression of ezrin in vagina cells of postmenopausal rats after dietary
      administration of omega-3 Fatty Acid formula.
AB  - OBJECTIVES: To see the effect of dietary administration of omega 3-fatty acid
      formula on the vaginal cells of postmenopausal rats. METHODS: Three-week-old
      female Wistar/ST rats were raised after one week of adjustment period. The rats
      were then divided into three groups, for three different kinds of diet; general
      diet, 1% omega-3 fatty acid diet, and 2% omega-3 fatty acid diet. After eight
      weeks of having assigned diet, after the oophorectomy, with the same diet
      previously they had Immunohistochemistry, Immunofluorescence, and Western Blot
      about ezrin, merlin were done. RESULTS: In immunohistochemistry, estrogen
      injection group revealed thicker and well differentiated features. In
      Immunofluorescence, Omega-3 fatty acid composition in diet did not effect
      expression of ezrin and merlin in rat vagina in estrogen injection group, their
      vaginal epithelium showed full layers (from basal to apical layer). In Western
      Blot analysis, Omega-3 fatty acid composition in diet did not affect expression
      of ezrin and merlin in rat vagina estrogen presented significant impact on
      expression of ezrin and merlin. CONCLUSION: Although omega-3 fatty acid
      composition changed in diet, vaginal epithelial morphology unchanged. Estrogen
      did effect on vagina cell, but omega-3 fatty acid did not effect on ezrin and
      merlin in vagina.

PMID- 25580421
TI  - Clinical and Biochemical Profiles according to Homeostasis Model Assessment
      insulin Resistance (HOMA-IR) in Korean Women with Polycystic Ovary Syndrome.
AB  - OBJECTIVES: The aim of this study was to investigate the clinical and biochemical
      profiles according to homeostasis model assessment of insulin resistance (HOMA
      IR) in Korean polycystic ovary syndrome (PCOS) patients. METHODS: In 458 PCOS
      patients diagnosed by the Rotterdam European Society for Human Reproduction and
      Embryology (ESHRE) criteria, measurements of somatometry, blood test of hormones,
      glucose metabolic and lipid profiles, and transvaginal or transrectal
      ultrasonogram were carried out. HOMA-IR was then calculated and compared with the
      clinical and biochemical profiles related to PCOS. The patients were divided into
      4 groups by quartiles of HOMA-IR. RESULTS: The mean level of HOMA-IR was 2.18 +/-
      1.73. Among the four groups separated according to HOMA-IR, body weight, body
      mass index (BMI), waist-to-hip ratio (WHR), triglyceride (TG), total cholesterol,
      high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL)
      cholesterol, lipid accumulation product (LAP) index, high-sensitivity C-reactive
      protein (hs-CRP), Apoprotein B, free testosterone, and sex hormone binding
      globulin (SHBG) were found to be significantly different. TG, LAP index, glucose
      metabolic profiles, and hs-CRP were positively correlated with HOMA-IR after
      adjustment for BMI. CONCLUSION: Our results suggest that the clinical and
      biochemical profiles which are applicable as cardiovascular risk factors are
      highly correlated with HOMA-IR in Korean women with PCOS.

PMID- 25580423
TI  - Menopause Knowledge, Attitude, Symptom and Management among Midlife Employed
      Women.
AB  - OBJECTIVES: Midlife women's knowledge, positive attitudes and management toward
      menopause may improve the quality of peri and post-menopause life. This study was
      to identify correlations of the knowledge, attitude, symptoms and management
      toward menopause in middle-aged women. METHODS: We used a cross-sectional
      questionnaire study applying to 231 perimenopausal and menopausal women aged from
      40 to 59 years old. The completed data of 189 perimenopausal and menopausal women
      were analyzed through t-test, ANOVA and pearson's correlation coefficient using
      the SPSS statistical programme. RESULTS: The menopausal women showed
      significantly higher physical symptoms than perimenopausal women. The menopausal
      women showed significantly higher psychosomatic symptom than perimenopausal
      women. There was a significant correlation between the menopausal attitude and
      management. CONCLUSION: This study suggests that the fundamental data of
      developing midlife women's symptom index (MSI) and providing menopause management
      could be a strategy to encourage successful menopausal transition in middle-aged
      women.

PMID- 25580422
TI  - Effect of transdermal estrogen therapy on bone mineral density in postmenopausal
      korean women.
AB  - OBJECTIVES: To evaluate the effects of transdermal estrogen therapy on bone
      mineral density (BMD) in postmenopausal Korean women. METHODS: A total of 149
      healthy postmenopausal women were retrospectively evaluated: 100 were on hormone
      therapy (HT) and 49 were the control group. For the HT group, 54 applied estrogen
      transdermally using either a patch (n = 21) or gel (n = 33), and 46 took estrogen
      orally (conjugated estrogen 0.625 mg or equivalent). Demographic profiles and
      changes in BMD over two years were compared according to the route of the
      estrogen. RESULTS: No differences were found in age, age at menopause, parity,
      body mass index, and type of menopause among the oral, transdermal and control
      groups. Compared with controls, HT significantly increased BMD after 2 years in
      both the lumbar spine and the total hip. The increases in BMD at both lumbar
      spine and hip were comparable between the oral and transdermal groups. There were
      also no differences in BMD changes according to progestogen addition in either
      the oral or transdermal groups. CONCLUSION: Transdermal estrogen therapy
      increases BMD, comparable to oral estrogen, in postmenopausal Korean women.

PMID- 25580424
TI  - The Association between Serum Uric Acid Level and Incidence of Metabolic Syndrome
      according to Menopausal Status in Korean Women.
AB  - OBJECTIVES: The aim of this study is to investigate the association between serum
      uric acid level and metabolic syndrome according to menopausal status in Korean
      women. METHODS: A total of 2,241 women who visited to the health promotion center
      at Pusan National University Hospital from 2010 to 2014 were included in this
      cross-sectional study. Self-report questionnaires and interviews with healthcare
      providers were used to assess disease history, medication history, menstrual
      history and body size measuring. Anthropometric measurements and laboratory
      results were compared as presence of metabolic syndrome and menopausal status by
      student-t test. Logistic regression analysis was performed between presence of
      metabolic syndrome and presumable predictive factors, such as age, menopause and
      serum uric acid. RESULTS: The prevalence rate of metabolic syndrome were 7.45%
      (63/846) in pre-menopausal group and 23.87% (333/1395) in menopausal group. Serum
      uric acid level was higher in menopausal women than premenopausal women (4.6 +/-
      1.1 vs. 4.3 +/- 0.9. P = 0.000). And, its concentration was also higher in
      metabolic syndrome than normal women regarding of menopausal statue (premenopause
      4.7 +/- 1.1 vs. 4.2 +/- 0.8, P = 0.001, menopause 4.9 +/- 1.3 vs. 4.5 +/- 1.0, P
      = 0.000). Multiple logistic regression analysis showed serum uric acid and age
      have relationship with metabolic syndrome (OR: 1.453, 95% confidence interval
      [CI]: 1.074-1.111, P = 0.000; OR: 1.092, 95% CI: 1.305-1.619, P = 0.000).
      CONCLUSION: We could find out some potential of uric acid as predictive factor
      for metabolic syndrome in premenopausal and menopausal group. Further
      investigation is required to clarify the relationship between serum uric acid,
      menopause and metabolic syndrome.

PMID- 25580425
TI  - Retroperitoneal leiomyoma of the uterus mimicking sarcoma in perimenopausal
      woman: case report.
AB  - Leiomyomas are very common benign tumors in the uterus and it is rare condition
      to present the retroperitoneal leiomyoma. The author reported a 48-year-old
      female patient who presented right pelvic mass with urinary incontinence and
      lower abdominal discomfort. Based on the preoperative imaging, provisional
      diagnosis was mesenchymal sarcoma. In the intraoperative findings, huge mass
      abutting to the uterus was observed in retroperitoneal space beneath the right
      broad ligament. After the exposure the retroperitoneal space, we encountered the
      well-demarcated tumor measuring 8 * 6 cm in diameter and this tumor attached the
      right surface of the uterus with fibrotic tissue. Pathologic findings
      demonstrated retroperitoneal uterine leiomyoma. 

PMID- 25580426
TI  - Exploring a clinically friendly web-based approach to clinical decision support
      linked to the electronic health record: design philosophy, prototype
      implementation, and framework for assessment.
AB  - BACKGROUND: Computer-based clinical decision support (CDS) is an important
      component of the electronic health record (EHR). As an increasing amount of CDS
      is implemented, it will be important that this be accomplished in a fashion that
      assists in clinical decision making without imposing unacceptable demands and
      burdens upon the provider's practice. OBJECTIVE: The objective of our study was
      to explore an approach that allows CDS to be clinician-friendly from a variety of
      perspectives, to build a prototype implementation that illustrates features of
      the approach, and to gain experience with a pilot framework for assessment.
      METHODS: The paper first discusses the project's design philosophy and goals. It
      then describes a prototype implementation (Neuropath/CDS) that explores the
      approach in the domain of neuropathic pain and in the context of the US Veterans
      Administration EHR. Finally, the paper discusses a framework for assessing the
      approach, illustrated by a pilot assessment of Neuropath/CDS. RESULTS: The paper
      describes the operation and technical design of Neuropath/CDS, as well as the
      results of the pilot assessment, which emphasize the four areas of focus, scope,
      content, and presentation. CONCLUSIONS: The work to date has allowed us to
      explore various design and implementation issues relating to the approach
      illustrated in Neuropath/CDS, as well as the development and pilot application of
      a framework for assessment.

PMID- 25580427
TI  - Emodin augments cisplatin cytotoxicity in platinum-resistant ovarian cancer cells
      via ROS-dependent MRP1 downregulation.
AB  - The intracellular level of reactive oxygen species (ROS) is closely associated
      with chemosensitivity of cancer cells. Overexpression of ATP binding cassette
      transporter MRP1 is correlated with resistance to platinum drugs. In this study,
      we tested the hypothesis that emodin, a potent ROS generator, may increase
      sensitivity of cisplatin-(cDDP-) resistant ovarian carcinoma cells to cDDP
      cytotoxicity via ROS-mediated suppression of MRP1 expression. Using the isogenic
      pair of the human ovarian carcinoma cell line COC1 and its cDDP resistant variant
      COC1/DDP, we found that ROS level in the cDDP-sensitive ovarian cancer cells was
      significantly higher than that in the cDDP-resistant cells. Emodin enhanced ROS
      production in COC1/DDP cells and consequently sensitized them to cDDP-induced
      apoptosis. These effects were reversed by addition of the antioxidant N-acetyl-L
      cysteine (NAC). Cotreatment with emodin and cDDP inhibited the tumor growth in
      vivo by increasing tumor cell apoptosis. The emodin-enhanced cDDP cytotoxicity
      was attributable to downregulation of multidrug resistance-related protein 1
      (MRP1) expression. Together, these results suggest that emodin could act as an
      adjunct to enhance the anticancer effect of cDDP likely through ROS-related
      downregulation of MRP1 expression, and may be of therapeutic potential in cDDP
      refractory ovarian carcinomas. 

PMID- 25580428
TI  - Impact of medical and surgical treatment of endometriosis on the cure of
      endometriosis and pain.
AB  - This endometriosis study evaluates three different treatment strategies (hormonal
      medication, surgical, or combined treatment) and discusses the influence of
      endometriosis on the cure of this disease and pain relief. Four hundred and fifty
      patients with genital endometriosis, aged 18-44 years, were randomly distributed
      to three treatment groups at the first laparoscopy. They were reevaluated at a
      second-look laparoscopy (D 426/10), one to two months after the three-month
      hormonal therapy for groups 1 and 3 and five to six months later for group 2
      (surgical treatment alone). Outcome data focussed on the recurrence of symptoms
      and pain. The three treatment options independent of the initial endoscopic
      endometriosis classification (EEC) stage including deep infiltrating
      endometriosis (DIE) achieved an overall cure rate of 50% or higher. The highest
      cure rate of 60% was achieved by the combined treatment, 55% by the exclusively
      hormonal therapy, and 50% by the exclusively surgical treatment. An overall
      pregnancy rate between 55% and 65% was achieved with no significant difference in
      relation to the therapeutical option. 

PMID- 25580429
TI  - Common polymorphism in the LRP5 gene may increase the risk of bone fracture and
      osteoporosis.
AB  - The low-density lipoprotein receptor-related protein 5 gene (LRP5) was identified
      to be linked to the variation in bone mineral density and types of bone diseases.
      The present study was aimed at examining the association of LRP5 rs3736228 C>T
      gene with bone fracture and osteoporosis by meta-analysis. A systematic
      electronic search of literature was conducted to identify all published studies
      in English or Chinese on the association of the LRP5 gene with bone fracture and
      osteoporosis risks. All analyses were calculated using the Version 12.0 STATA
      software. Odds ratios (ORs) and their corresponding 95% confidence interval (95%
      CI) were calculated. An updated meta-analysis was currently performed, including
      seven independent case-control studies. Results identified that carriers of
      rs3736228 C>T variant in the LRP5 gene were associated with an increased risk of
      developing osteoporosis and fractures under 4 genetic models but not under the
      dominant model (OR = 1.19, 95% CI = 0.97~1.46, and P = 0.103). Ethnicity-subgroup
      analysis implied that LRP5 rs3736228 C>T mutation was more likely to develop
      osteoporosis and fractures among Asians and Caucasians in majority of subgroups.
      These results suggest that there is a modest effect of the LRP5 rs3736228 C>T on
      the increased susceptibility of bone fracture and osteoporosis. 

PMID- 25580430
TI  - Association analysis between g.18873C>T and g.27522G>A genetic polymorphisms of
      OPG and bone mineral density in Chinese postmenopausal women.
AB  - Several studies report that the OPG is an important candidate gene in the
      pathogenesis of osteoporosis. This study aimed to detect the potential
      association of OPG gene polymorphisms with osteoporosis in postmenopausal women.
      We recruited 928 subjects containing 463 with primary postmenopausal osteoporosis
      and 465 healthy volunteers as controls. The BMD of neck hip, lumbar spine (L(2
      4)), and total hip were assessed by dual-energy X-ray absorptiometry (DEXA).
      Through the created restriction site-polymerase chain reaction (CRS-PCR), PCR
      restriction fragment length polymorphism (PCR-RFLP), and DNA sequencing methods,
      the g.18873C>T and g.27522G>A have been investigated. As for g.18873C>T, our data
      indicated that subjects with CC genotype have significantly higher BMD value than
      those of CT and TT genotypes (all P values < 0.05). As for g.27522G>A, the BMD
      values of subjects with GG genotype were significantly higher than those of GA
      and AA genotypes (all P values < 0.05). Our findings suggest that the OPG
      g.18873C>T and g.27522G>A genetic polymorphisms are associated with the decreased
      risk for osteoporosis in Chinese postmenopausal women.

PMID- 25580431
TI  - Iron as the key modulator of hepcidin expression in erythroid antibody-mediated
      hypoplasia.
AB  - Erythroid hypoplasia (EH) is a rare complication associated with recombinant
      human erythropoietin (rHuEPO) therapies, due to development of anti-rHuEPO
      antibodies; however, the underlying mechanisms remain poorly clarified. Our aim
      was to manage a rat model of antibody-mediated EH induced by rHuEPO and study the
      impact on iron metabolism and erythropoiesis. Wistar rats treated during 9 weeks
      with a high rHuEPO dose (200 IU) developed EH, as shown by anemia, reduced
      erythroblasts, reticulocytopenia, and plasmatic anti-rHuEPO antibodies. Serum
      iron was increased and associated with mRNA overexpression of hepatic hepcidin
      and other iron regulatory mediators and downregulation of matriptase-2;
      overexpression of divalent metal transporter 1 and ferroportin was observed in
      duodenum and liver. Decreased EPO expression was observed in kidney and liver,
      while EPO receptor was overexpressed in liver. Endogenous EPO levels were normal,
      suggesting that anti-rHuEPO antibodies blunted EPO function. Our results suggest
      that anti-rHuEPO antibodies inhibit erythropoiesis causing anemia. This leads to
      a serum iron increase, which seems to stimulate hepcidin expression despite no
      evidence of inflammation, thus suggesting iron as the key modulator of hepcidin
      synthesis. These findings might contribute to improving new therapeutic
      strategies against rHuEPO resistance and/or development of antibody-mediated EH
      in patients under rHuEPO therapy.

PMID- 25580432
TI  - A single imaging modality in the diagnosis, severity, and prognosis of pulmonary
      embolism.
AB  - INTRODUCTION: This study aimed to investigate the currency of computerized
      tomography pulmonary angiography-based parameters as pulmonary artery obstruction
      index (PAOI), as well as right ventricular diameters for pulmonary embolism (PE)
      risk evaluation and prediction of mortality and intensive care unit (ICU)
      requirement. MATERIALS AND METHODS: The study retrospectively enrolled 203
      patients hospitalized with acute PE. PAOI was calculated according to Qanadli
      score. RESULTS: Forty-three patients (23.9%) were hospitalized in the ICU.
      Nineteen patients (10.6%) died during the 30-day follow-up period. The optimal
      cutoff value of PAOI for PE 30th day mortality and ICU requirement were found as
      36.5% in ROC curve analysis. The pulmonary artery systolic pressure had a
      significant positive correlation with right/left ventricular diameter ratio (r =
      0.531, P < 0.001), PAOI (r = 0.296, P < 0.001), and pulmonary artery diameter (r
      = 0.659, P < 0.001). The patients with PAOI values higher than 36.5% have a 5.7
      times increased risk of death. CONCLUSION: PAOI is a fast and promising parameter
      for risk assessment in patients with acute PE. With greater education of
      clinicians in this radiological scoring, a rapid assessment for diagnosis,
      clinical risk evaluation, and prognosis may be possible in emergency services
      without the need for echocardiography.

PMID- 25580433
TI  - Preparation and characterization of gelatin-based mucoadhesive nanocomposites as
      intravesical gene delivery scaffolds.
AB  - This study aimed to develop optimal gelatin-based mucoadhesive nanocomposites as
      scaffolds for intravesical gene delivery to the urothelium. Hydrogels were
      prepared by chemically crosslinking gelatin A or B with glutaraldehyde.
      Physicochemical and delivery properties including hydration ratio, viscosity,
      size, yield, thermosensitivity, and enzymatic degradation were studied, and
      scanning electron microscopy (SEM) was carried out. The optimal hydrogels (H),
      composed of 15% gelatin A175, displayed an 81.5% yield rate, 87.1% hydration
      ratio, 42.9 Pa.s viscosity, and 125.8 nm particle size. The crosslinking density
      of the hydrogels was determined by performing pronase degradation and ninhydrin
      assays. In vitro lentivirus (LV) release studies involving p24 capsid protein
      analysis in 293T cells revealed that hydrogels containing lentivirus (H-LV) had a
      higher cumulative release than that observed for LV alone (3.7-, 2.3-, and 2.3
      fold at days 1, 3, and 5, resp.). Lentivirus from lentivector constructed green
      fluorescent protein (GFP) was then entrapped in hydrogels (H-LV-GFP). H-LV-GFP
      showed enhanced gene delivery in AY-27 cells in vitro and to rat urothelium by
      intravesical instillation in vivo. Cystometrogram showed mucoadhesive H-LV
      reduced peak micturition and threshold pressure and increased bladder compliance.
      In this study, we successfully developed first optimal gelatin-based mucoadhesive
      nanocomposites as intravesical gene delivery scaffolds. 

PMID- 25580434
TI  - Specific genomic fingerprints of phosphate solubilizing Pseudomonas strains
      generated by BOX elements.
AB  - Primers corresponding to conserved bacterial repetitive of BOX elements were used
      to show that BOX-DNA sequences are widely distributed in phosphate solubilizing
      Pseudomonas strains. Phosphate solubilizing Pseudomonas was isolated from oil
      palm fields (tropical soil) in Malaysia. BOX elements were used to generate
      genomic fingerprints of a variety of Pseudomonas isolates to identify strains
      that were not distinguishable by other classification methods. BOX-PCR, that
      derived genomic fingerprints, was generated from whole purified genomic DNA by
      liquid culture of phosphate solubilizing Pseudomonas. BOX-PCR generated the
      phosphate solubilizing Pseudomonas specific fingerprints to identify the
      relationship between these strains. This suggests that distribution of BOX
      elements' sequences in phosphate solubilizing Pseudomonas strains is the mirror
      image of their genomic structure. Therefore, this method appears to be a rapid,
      simple, and reproducible method to identify and classify phosphate solubilizing
      Pseudomonas strains and it may be useful tool for fast identification of
      potential biofertilizer strains. 

PMID- 25580436
TI  - Sequential coordination between lingual and pharyngeal pressures produced during
      dry swallowing.
AB  - The aim of this study was to investigate oropharyngeal pressure flow dynamics
      during dry swallowing in ten healthy subjects. Tongue pressure (TP) was measured
      using a sensor sheet system with five measuring points on the hard palate, and
      pharyngeal pressure (PP) was measured using a manometric catheter with four
      measuring points. The order and correlations of sequential events, such as onset,
      peak, and offset times of pressure production, at each pressure measuring point
      were analyzed on the synchronized waveforms. Onset of TP was earlier than that of
      PP. The peak of TP did not show significant differences with the onset of PP, and
      it was earlier than that of PP. There was no significant difference between the
      offset of TP and PP. The onset of PP was temporally time-locked to the peak of
      TP, and there was an especially strong correlation between the onset of PP and TP
      at the posterior-median part on the hard palate. The offset of PP was temporally
      time-locked to that of TP. These results could be interpreted as providing an
      explanation for the generation of oropharyngeal pressure flow to ensure efficient
      bolus transport and safe swallowing. 

PMID- 25580437
TI  - ECR-MAPK regulation in liver early development.
AB  - Early growth is connected to a key link between embryonic development and aging.
      In this paper, liver gene expression profiles were assayed at postnatal day 22
      and week 16 of age. Meanwhile another independent animal experiment and cell
      culture were carried out for validation. Significance analysis of microarrays,
      qPCR verification, drug induction/inhibition assays, and metabonomics indicated
      that alpha-2u globulin (extracellular region)-socs2 (-SH2-containing
      signals/receptor tyrosine kinases)-ppp2r2a/pik3c3 (MAPK signaling)-hsd3b5/cav2
      (metabolism/organization) plays a vital role in early development. Taken
      together, early development of male rats is ECR and MAPK-mediated coordination of
      cancer-like growth and negative regulations. Our data represent the first
      comprehensive description of early individual development, which could be a
      valuable basis for understanding the functioning of the gene interaction network
      of infant development. 

PMID- 25580438
TI  - Identification of a marine Bacillus strain C5 and parathion-methyl degradation
      characteristics of the extracellular esterase B1.
AB  - A bacterial strain C5 that can produce new type of marine esterase was isolated
      and screened from marine sludge. According to 16S rRNA sequence analysis and
      physiological and biochemical experiments, the strain was identified as Bacillus
      subtilis. A single isozyme with a molecular weight of 86 kDa was observed by SDS
      PAGE and native-PAGE. On this basis, the mechanism of esterase B1 secreted by
      strain C5 degrading parathion-methyl was explored, and the effects of temperature
      and pH on the degradation rate were investigated. From the results, p-nitrophenol
      was one of the degradation products of B1 degrading parathion-methyl, and the
      best degradation effect could be achieved at the temperature of 40 degrees C and
      the neutral pH value. 

PMID- 25580439
TI  - Risk factors for hospital and long-term mortality of critically ill elderly
      patients admitted to an intensive care unit.
AB  - BACKGROUND: Data on long-term outcomes of elderly (>=65 years) patients in ICU
      are sparse. MATERIALS AND METHODS: Adult patients (n = 1563, 45.4% elderly)
      admitted over 28 months were analyzed by competing risks regression model to
      determine independent factors related to in-hospital and long-term mortality.
      RESULTS: 414 (26.5%) and 337 (21.6%) patients died in-hospital and during the 52
      months following discharge, respectively; the elderly group had higher mortality
      during both periods. After discharge, elderly patients had 2.3 times higher
      mortality compared to the general population of the same age-group. In-hospital
      mortality was independently associated with mechanical ventilation
      (subdistribution hazard ratio (SHR) 2.74), vasopressors (SHR 2.56), neurological
      disease (SHR 1.77), and Mortality Prediction Model II score (SHR 1.01) regardless
      of age and with malignancy (SHR, hematological 3.65, nonhematological 3.4) and
      prior renal replacement therapy (RRT, SHR 2.21) only in the elderly. Long-term
      mortality was associated with low hemoglobin concentration (SHR 0.94), airway
      disease (SHR 2.23), and malignancy (SHR hematological 1.11, nonhematological
      2.31) regardless of age and with comorbidities especially among the nonelderly.
      CONCLUSIONS: Following discharge, elderly ICU patients have higher mortality
      compared to the nonelderly and general population. In the elderly group, prior
      RRT and malignancy contribute additionally to in-hospital mortality risk. In the
      long-term, comorbidities (age-related), anemia, airway disease, and malignancy
      were significantly associated with mortality.

PMID- 25580435
TI  - Understanding host-adherent-invasive Escherichia coli interaction in Crohn's
      disease: opening up new therapeutic strategies.
AB  - A trillion of microorganisms colonize the mammalian intestine. Most of them have
      coevolved with the host in a symbiotic relationship and some of them have
      developed strategies to promote their replication in the presence of competing
      microbiota. Recent evidence suggests that perturbation of the microbial community
      favors the emergence of opportunistic pathogens, in particular adherent-invasive
      Escherichia coli (AIEC) that can increase incidence and severity of gut
      inflammation in the context of Crohn's disease (CD). This review will report the
      importance of AIEC as triggers of intestinal inflammation, focusing on their
      impact on epithelial barrier function and stimulation of mucosal inflammation.
      Beyond manipulation of immune response, restoration of gut microbiota as a new
      treatment option for CD patients will be discussed. 

PMID- 25580441
TI  - Posttraumatic Stress Symptoms in Parents of Pediatric Cancer Patients: A
      Mediational Analysis.
AB  - OBJECTIVE: Prior research finds that anxiety and depression among parents of
      pediatric cancer patients are associated with posttraumatic stress symptoms in
      response to children's cancer. This study examined whether this relationship is
      mediated by parents' negative affective reactions in response to their children's
      cancer-related treatment procedures. METHODS: Participants were parents of 101
      patients within six months of diagnosis who had completed at least two treatment
      related procedures. Parents completed measures of trait anxiety and depression at
      baseline and posttraumatic stress symptoms at 3-month follow-up assessment. On
      the day of each treatment procedure, parents completed measures of state anxiety
      immediately before and negative mood and distress immediately after the
      procedure. RESULTS: Trait anxiety was positively associated with state anxiety
      immediately before procedures and negative mood after procedures. Depression was
      positively associated with state anxiety immediately before procedures and
      negative mood and distress after procedures. Both trait anxiety and depression
      were positively associated with posttraumatic stress symptoms at 3-months follow
      up. Parent state anxiety, negative mood, and distress partially mediated the
      effects of trait anxiety and/or depression on posttraumatic stress symptoms.
      Controlling for child age and social desirability did not affect these
      relationships. CONCLUSIONS: Parents' trait anxiety and depression may influence
      cancer-related posttraumatic stress partially through their effect on parents'
      negative affective reactions at the time of their child's treatment procedures.
      These findings provide a more nuanced understanding of how parents' affect in
      response to procedures contributes to parent posttraumatic stress and suggest
      that interventions targeting treatment-related affective reactions of parents
      with high trait anxiety and/or depression may reduce the risk for longer-term
      distress and posttraumatic stress symptoms.

PMID- 25580440
TI  - The GLP-1 analogue exenatide improves hepatic and muscle insulin sensitivity in
      diabetic rats: tracer studies in the basal state and during hyperinsulinemic
      euglycemic clamp.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase
      insulin secretion in diabetes but less is known about their effects on glucose
      production or insulin-stimulated glucose uptake in peripheral tissues. METHODS:
      Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C);
      nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with
      diabetes induced by streptozotocin and high fat diet. Infusion of 3-(3)H-glucose
      and U-(13)C-glycerol was used to measure basal rates of appearance (Ra) of
      glucose and glycerol and gluconeogenesis from glycerol (GNG). During
      hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was
      measured with 2-deoxy-D-(14)C-glucose. RESULTS: In the diabetic rats, exenatide
      reduced the basal Ra of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P <
      0.001). During the clamp, Ra of glucose was also reduced, whereas the rate of
      disappearance of glucose increased and there was increased glucose uptake into
      muscle (P < 0.01) during the clamp. In the nondiabetic rats, exenatide had no
      effect. CONCLUSION: In addition to its known effects on insulin secretion,
      administration of the GLP-1 analogue, exenatide, is associated with increased
      inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic
      rats, implying improved hepatic and peripheral insulin sensitivity.

PMID- 25580442
TI  - Integrated Cognitive Behavioral Therapy (ICBT) For PTSD and Substance Use in Iraq
      and Afghanistan Veterans: A Feasibility Study.
AB  - Co-occurring posttraumatic stress disorder (PTSD) and substance use disorder
      (SUD) is prevalent in military Veterans and is associated with poorer outcomes
      than either disorder alone. The current pilot study examines the feasibility of
      delivering integrated cognitive behavioral therapy (ICBT) for co-occurring PTSD
      SUD to Veterans who served in Iraq and Afghanistan. Our primary aims were testing
      the feasibility of engaging and retaining Veterans with a complex clinical
      presentation in a 12-week structured therapy. We focused on two feasibility
      outcomes: 1) acceptability; and 2) tolerability. We also examined clinically
      meaningful change in PTSD and depressive symptoms as a secondary aim. Over the
      course of the study, we recruited 12 eligible Veterans, 6 of whom completed ICBT.
      We encountered challenges related to engaging and retaining Veterans in treatment
      and discuss adaptations and refinements of ICBT or other integrated treatments
      for returning Veterans with co-occurring PTSD-SUD to increase feasibility with
      military Veterans.

PMID- 25580444
TI  - Cyproheptadine-Induced Acute Liver Failure.
AB  - We present the case of a 55-year-old white female with no history of liver or
      gastrointestinal disease, admitted with acute liver failure following a trial of
      cyproheptadine for appetite stimulation. The patient was managed with supportive
      care, symptomatic treatment, and discontinuation of cyproheptadine. To our
      knowledge, this is the first described case of cyproheptadine-induced acute liver
      failure in over 20 years.

PMID- 25580443
TI  - Affective Brain-Computer Interfaces As Enabling Technology for Responsive
      Psychiatric Stimulation.
AB  - There is a pressing clinical need for responsive neurostimulators, which sense a
      patient's brain activity and deliver targeted electrical stimulation to suppress
      unwanted symptoms. This is particularly true in psychiatric illness, where
      symptoms can fluctuate throughout the day. Affective BCIs, which decode emotional
      experience from neural activity, are a candidate control signal for responsive
      stimulators targeting the limbic circuit. Present affective decoders, however,
      cannot yet distinguish pathologic from healthy emotional extremes. Indiscriminate
      stimulus delivery would reduce quality of life and may be actively harmful. We
      argue that the key to overcoming this limitation is to specifically decode
      volition, in particular the patient's intention to experience emotional
      regulation. Those emotion-regulation signals already exist in prefrontal cortex
      (PFC), and could be extracted with relatively simple BCI algorithms. We describe
      preliminary data from an animal model of PFC-controlled limbic brain stimulation
      and discuss next steps for pre-clinical testing and possible translation.

PMID- 25580445
TI  - Adeno-associated viral (AAV) vectors do not efficiently target muscle satellite
      cells.
AB  - Adeno-associated viral (AAV) vectors are becoming an important tool for gene
      therapy of numerous genetic and other disorders. Several recombinant AAV vectors
      (rAAV) have the ability to transduce striated muscles in a variety of animals
      following intramuscular and intravascular administration, and have attracted
      widespread interest for therapy of muscle disorders such as the muscular
      dystrophies. However, most studies have focused on the ability to transduce
      mature muscle cells, and have not examined the ability to target myogenic stem
      cells such as skeletal muscle satellite cells. Here we examined the relative
      ability of rAAV vectors derived from AAV6 to target myoblasts, myocytes and
      myotubes in culture and satellite cells and myofibers in vivo. AAV vectors are
      able to transduce proliferating myoblasts in culture, albeit with reduced
      efficiency relative to post-mitotic myocytes and myotubes. In contrast, quiescent
      satellite cells are refractory to transduction in adult mice. These results
      suggest that while muscle disorders characterized by myofiber regeneration can be
      slowed or halted by AAV transduction, little if any vector transduction can be
      obtained in myogenic stems cells that might other wise support ongoing muscle
      regeneration.

PMID- 25580447
TI  - Mitomycin C reduces abundance of replication forks but not rates of fork
      progression in primary and transformed human cells.
AB  - DNA crosslinks can block replication in vitro and slow down S phase progression
      in vivo. We characterized the effect of mitomycin C crosslinker on S phase
      globally and on individual replication forks in wild type and FANCD2-deficient
      human cells. FANCD2 is critical to crosslink repair, and is also implicated in
      facilitating DNA replication. We used DNA fiber analysis to demonstrate
      persistent reduction in abundance but not progression rate of replication forks
      during an S phase of MMC-treated cells. FANCD2 deficiency did not eliminate this
      phenotype. Immunoprecipitation of EdU-labeled DNA indicated that replication was
      not suppressed in the domains that were undergoing response to MMC as marked by
      the presence of gammaH2AX, and in fact gammaH2AX was overrepresented on DNA that
      had replicated immediately after MMC in wild type through less so in FANCD2
      depleted cells. FANCD2-depleted cells also produced fewer tracks of uninterrupted
      replication of up to 240Kb long, regardless of MMC treatment. Overall, the data
      suggest that crosslinks may not pose a block to S phase as a whole, but instead
      profoundly change its progress by reducing density of replication forks and
      causing at least a fraction of forks to operate within a DNA damage response
      altered chromatin.

PMID- 25580448
TI  - Resolution of chronic ocular sarcoidosis with antimycobacterial therapy.
AB  - Ocular and cutaneous sarcoidosis is a chronic manifestation of sarcoidosis that
      remains difficult to treat. Recent investigations demonstrating efficacy with
      antimicrobial therapy in pulmonary and cutaneous sarcoidosis have been reported.
      Here, we report dual clinical improvement in cutaneous and ocular sarcoidosis
      following administration of oral antimycobacterial therapy.

PMID- 25580449
TI  - Effects of Three Low-Doses of D-Tagatose on Glycemic Control Over Six Months in
      Subjects with Mild Type 2 Diabetes Mellitus Under Control with Diet and Exercise.
AB  - The primary objective of this study was to evaluate the safety and the effect of
      D-tagatose on the glycemic control of subjects with type 2 diabetes as determined
      by HbA1c levels at the end of 6 months of therapy using the subject's own
      baseline HbA1c level as a comparator. The determination of the minimal dose
      required to cause a statistically significant reduction in HbA1c was of
      particular interest. Eight weeks after screening, the qualifying subjects were
      randomized to receive one of three doses of D-tagatose: 2.5 g TID, 5.0 g TID or
      7.5 g TID. Blood levels of HbA1c, fasting blood glucose concentrations, plasma
      lipids, changes in body weight, changes in body mass index, and change in insulin
      levels were checked at each study visit and at the end of the study. Treatment
      success, as measured by the reduction of HbA1c, was greatest for the 7.5 g D
      tagatose dose group, although the difference between the treatments was not
      statistically significant. For fasting glucose, only the 7.5 g dosage group
      exhibited reductions from baseline at the 3- and 6-month time points. Mean body
      weights reduced in a dose-response fashion, with the 5.0 g and the 7.5 g D
      tagatose doses providing the greatest reductions. D-tagatose at dosages of 2.5 g,
      5.0 g, and 7.5 g TID for six months were well tolerated by this subject
      population. D-tagatose at 5.0 g TID was the minimal dose required to reduce
      HbA1c. D-tagatose at 7.5 g TID provided the greatest effect in most measured
      efficacy parameters.

PMID- 25580451
TI  - Rapid reduction in breast cancer mortality with inorganic arsenic in drinking
      water.
AB  - BACKGROUND: Arsenic trioxide is effective in treating promyelocytic leukemia, and
      laboratory studies demonstrate that arsenic trioxide causes apoptosis of human
      breast cancer cells. Region II in northern Chile experienced very high
      concentrations of inorganic arsenic in drinking water, especially in the main
      city Antofagasta from 1958 until an arsenic removal plant was installed in 1970.
      METHODS: We investigated breast cancer mortality from 1950 to 2010 among women in
      Region II compared to Region V, which had low arsenic water concentrations. We
      conducted studies on human breast cancer cell lines and compared arsenic exposure
      in Antofagasta with concentrations inducing apoptosis in laboratory studies.
      FINDINGS: Before 1958, breast cancer mortality rates were similar, but in 1958
      1970 the rates in Region II were half those in Region V (rate ratio RR = 0.51,
      95% CI 0.40-0.66; p<0.0001). Women under the age of 60 experienced a 70%
      reduction in breast cancer mortality during 1965-1970 (RR=0.30, 0.17-0.54;
      p<0.0001). Breast cancer cell culture studies showed apoptosis at arsenic
      concentrations close to those estimated to have occurred in people in Region II.
      INTERPRETATION: We found biologically plausible major reductions in breast cancer
      mortality during high exposure to inorganic arsenic in drinking water which could
      not be attributed to bias or confounding. We recommend clinical trial assessment
      of inorganic arsenic in the treatment of advanced breast cancer.

PMID- 25580452
TI  - Preliminary anticonvulsant and toxicity screening of substituted
      benzylidenehydrazinyl-N-(6-substituted benzo[d]thiazol-2-yl)propanamides.
AB  - Keeping in view the structural requirements suggested in the pharmacophore model
      for anticonvulsant activity, a new series of 3-(2
      (substitutedbenzylidene)hydrazinyl)-N-(substituted benzo[d]thiazol-2-yl)
      propanamides were synthesized with aromatic hydrophobic aryl ring (A), NH-C=O as
      hydrogen bonding domain (HBD), nitrogen atom as electron donor (D), and phenyl as
      distal aryl ring (C). Synthesized compounds were characterized by FTIR, (1)H NMR,
      (13)C NMR, mass spectroscopy, and elemental analysis. Preliminary in vivo
      anticonvulsant screening (phase I) was performed by two most adopted seizure
      models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole
      (scPTZ). Based on anticonvulsant screening results, two compounds, 5h and 5p,
      were found to be most active; they exhibited activity comparable to standard
      drugs phenytoin (PHY) and carbamazepine (CBZ). These active compounds were
      subjected to phase II and phase III screening, where they displayed much higher
      protective index (PI) in comparison to the standard drugs. In phase IV screening,
      the bioavailability of active compounds was assessed on oral administration.
      Further, preliminary safety profiles of 5h and 5p were evaluated by the
      neurotoxicity testing and liver enzyme estimation.

PMID- 25580450
TI  - Resilience to the effects of social stress: evidence from clinical and
      preclinical studies on the role of coping strategies.
AB  - The most common form of stress encountered by people stems from one's social
      environment and is perceived as more intense than other types of stressors. One
      feature that may be related to differential resilience or vulnerability to stress
      is the type of strategy used to cope with the stressor, either active or passive
      coping. This review focuses on models of social stress in which individual
      differences in coping strategies produce resilience or vulnerability to the
      effects of stress. Neurobiological mechanisms underlying these individual
      differences are discussed. Overall, the literature suggests that there are
      multiple neural mechanisms that underlie individual differences in stress-induced
      resilience and vulnerability. How these mechanisms interact with one another to
      produce a resilient or vulnerable phenotype is not understood and such mechanisms
      have been poorly studied in females and in early developmental periods. Finally,
      we propose that resilience may be stress context specific and resilience
      phenotypes may need to be fine-tuned to suit a shifting environment.

PMID- 25580453
TI  - Effect of the carbon concentration, blend concentration, and renewal rate in the
      growth kinetic of Chlorella sp.
AB  - The microalgae cultivation can be used as alternative sources of food, in
      agriculture, residual water treatment, and biofuels production. Semicontinuous
      cultivation is little studied but is more cost-effective than the discontinuous
      (batch) cultivation. In the semicontinuous cultivation, the microalga is
      maintained in better concentration of nutrients and the photoinhibition by
      excessive cell is reduced. Thus, biomass productivity and biocompounds of
      interest, such as lipid productivity, may be higher than in batch cultivation.
      The objective of this study was to examine the influence of blend concentration,
      medium renewal rate, and concentration of sodium bicarbonate on the growth of
      Chlorella sp. during semicontinuous cultivation. The cultivation was carried out
      in Raceway type bioreactors of 6 L, for 40 d at 30 degrees C, 41.6 umol m(-2) s(
      1), and a 12 h light/dark photoperiod. Maximum specific growth rate (0.149 d(-1))
      and generating biomass (2.89 g L(-1)) were obtained when the blend concentration
      was 0.80 g L(-1), the medium renewal rate was 40%, and NaHCO3 was 1.60 g L(-1).
      The average productivity (0.091 g L(-1) d(-1)) was achieved with 0.8 g L(-1) of
      blend concentration and NaHCO3 concentration of 1.6 g L(-1), independent of the
      medium renewal rate.

PMID- 25580454
TI  - Methods, diagnostic criteria, cutoff points, and prevalence of sarcopenia among
      older people.
AB  - AIM: To identify methods, index, diagnostic criteria, and corresponding cutoff
      points used to estimate the prevalence of sarcopenia in older people in different
      countries. METHODS: A systematic review was carried out in accordance with PRISMA
      Statement. The search encompassed the MEDLINE and LILACS databases and was
      executed during March 2012 using the keyword sarcopenia. RESULTS: A total of 671
      studies were identified by the search strategy, and 30 meet all inclusion
      criteria. Specifically for dual-X-ray absorptiometry, prevalence ranged from 2.2%
      to 95% in men and from 0.1% to 33.9% in women. For bioelectrical impedance
      analysis, the range was from 6.2% to 85.4% in men and 2.8% to 23.6% in women.
      Regarding anthropometric and computed tomography, prevalence rates were,
      respectively, 14.1% and 55.9%. CONCLUSIONS: Heterogeneity in prevalence of
      sarcopenia was identified, due to diagnostic method choice, cutoff points, and,
      characteristics of the population as well as reference population. These factors
      should be considered in research designs to enable comparison and validation of
      results. Despite the limitations of most studies that indicated high prevalence
      rates, the results indicate the need for early detection of this syndrome.

PMID- 25580455
TI  - Development, characterization, and pharmacodynamic evaluation of
      hydrochlorothiazide loaded self-nanoemulsifying drug delivery systems.
AB  - The objective of the current work was to develop optimized self-nanoemulsifying
      drug delivery systems (SNEDDS) and evaluate their in vitro and in vivo
      performance. The research comprised various studies which includes solubility
      studies in various vehicles, pseudoternary phase diagram construction, and
      preparation and characterization of SNEDDS along with in vitro dissolution and in
      vivo pharmacodynamic profiling. Based on dissolution profile, a remarkable
      increase in rate of dissolution was observed in comparison with plain drug and
      marketed formulation. Optimized SNEDDS formulation was composed of Capmul MCM
      (19.17% w/w), Tween 80 (57.5% w/w), Transcutol P (12.7% w/w), and HCT (4.17%
      w/w). In vivo pharmacodynamic evaluation in Wistar rats showed considerable
      increase in pharmacological effect of HCT by SNEDDS formulation as compared with
      plain HCT.

PMID- 25580457
TI  - Selection of superior lentil (Lens esculenta M.) genotypes by assessing character
      association and genetic diversity.
AB  - Lentil is one of the most important pulse crops in the world as well as in
      Bangladesh. It is now considered a main component for training and body building
      practising in first world countries. Yield varies tremendously from year to year
      and location to location. Therefore, it is very important to find genotypes that
      perform consistently well even in ecological farming systems without any
      intercultural operations. Twenty lentil genotypes were tested during the period
      from November 2010 to March 2011 and from December 2011 to March 2012 with three
      replicates in each season to determine genetic variability, diversity, characters
      association, and selection indices for better grain yield. The experiment was
      conducted at the breeding field of the Department of Genetics and Plant Breeding,
      Bangladesh Agricultural University, Mymensingh. This study revealed that all the
      genotypes possess a high amount of genetic diversity. Plant height and 100-grain
      weight showed significant positive correlation with grain yield plant(-1) that
      was also confirmed by path analysis as the highest direct effect on grain yield.
      The genotypes BM-513 and BM-941 were found to be the best performer in both the
      seasons and were considered as consistent genotype. The genotypes were grouped
      into four clusters based on Euclidean distance following Ward's method and RAPD
      analysis. However, discriminant function analysis revealed a progressive increase
      in the efficiency of selection and BM-70 ranked as the best followed by the
      genotypes BM-739, BM-680, BM-185, and BM-513. These genotypes might be
      recommended for farmers' cultivation in ecological farming in Bangladesh.

PMID- 25580458
TI  - Accuracy-energy configurable sensor processor and IoT device for long-term
      activity monitoring in rare-event sensing applications.
AB  - A specially designed sensor processor used as a main processor in IoT (internet
      of-thing) device for the rare-event sensing applications is proposed. The IoT
      device including the proposed sensor processor performs the event-driven sensor
      data processing based on an accuracy-energy configurable event-quantization in
      architectural level. The received sensor signal is converted into a sequence of
      atomic events, which is extracted by the signal-to-atomic-event generator (AEG).
      Using an event signal processing unit (EPU) as an accelerator, the extracted
      atomic events are analyzed to build the final event. Instead of the sampled raw
      data transmission via internet, the proposed method delays the communication with
      a host system until a semantic pattern of the signal is identified as a final
      event. The proposed processor is implemented on a single chip, which is tightly
      coupled in bus connection level with a microcontroller using a 0.18 MUm CMOS
      embedded-flash process. For experimental results, we evaluated the proposed
      sensor processor by using an IR- (infrared radio-) based signal reflection and
      sensor signal acquisition system. We successfully demonstrated that the expected
      power consumption is in the range of 20% to 50% compared to the result of the
      basement in case of allowing 10% accuracy error.

PMID- 25580456
TI  - How do metal ion levels change over time in hip resurfacing patients? A cohort
      study.
AB  - Metal-on-metal hip resurfacing (MOM-HR) is offered as an alternative to
      traditional hip arthroplasty for young, active adults with advanced
      osteoarthritis. Nevertheless, concerns remain regarding wear and corrosion of the
      bearing surfaces and the resulting increase in metal ion levels. We evaluated
      three cohorts of patients with Birmingham hip resurfacing (BHR) at an average
      follow-up of 2, 5, and 9 years. We asked whether there would be differences in
      ion levels between the cohorts and inside the gender. Nineteen patients were
      prospectively analyzed. The correlation with clinical-radiographic data was also
      performed. Chromium, cobalt, nickel, and molybdenum concentrations were measured
      by atomic absorption spectrophotometry. Chromium and cobalt levels demonstrated a
      tendency to decrease over time. Such tendency was present only in females. An
      inverse correlation between chromium, implant size, and Harris hip score was
      present at short term; it disappeared over time together with the decreased ion
      levels. The prospective analysis showed that, although metal ion levels remained
      fairly constant within each patient, there was a relatively large variation
      between subjects, so mean data in this scenario must be interpreted with caution.
      The chronic high exposure should be carefully considered during implant
      selection, particularly in young subjects, and a stricter monitoring is
      mandatory.

PMID- 25580459
TI  - An improved effective cost review process for value engineering.
AB  - Second-look value engineering (VE) is an approach that aims to lower the costs of
      products for which target costs are not being met during the production stage.
      Participants in second-look VE typically come up with a variety of ideas for cost
      cutting, but the outcomes often depend on their levels of experience, and not
      many good alternatives are available during the production stage. Nonetheless,
      good ideas have been consistently generated by VE experts. This paper
      investigates past second-look VE cases and the thinking processes of VE experts
      and proposes a cost review process as a systematic means of investigating cost
      cutting ideas. This cost review process includes the use of an idea checklist and
      a specification review process. In addition to presenting the process, this paper
      reports on its feasibility, based on its introduction into a VE training course
      as part of a pilot study. The results indicate that the cost review process is
      effective in generating ideas for later analysis.

PMID- 25580460
TI  - Undernutrition and its correlates among children of 3-9 years of age residing in
      slum areas of Bhubaneswar, India.
AB  - Undernutrition among children is a major public health concern worldwide, more
      prevalent in Asia and Africa. It manifests itself in various forms such as
      wasting or stunting or underweight and retards physical and mental development,
      increases susceptibility to infection, and reduces educational attainment and
      productivity. The present study was undertaken to assess the level of wasting,
      stunting, and underweight and determine its associates among slum children of 3-9
      years of age, residing in Bhubaneswar city, India. After obtaining informed
      consent, a total of 249 children from 249 households were studied and their
      parents/guardians were interviewed to collect all relevant information. 23.3%,
      57.4%, and 45.4% of children were found to have wasting, stunting, and
      underweight, respectively. Variables like birth order of child, period of
      initiation of breastfeeding and mother's education were found to be strong
      predictors of wasting, whereas toilet facility in household and practice of
      drinking water storage were significantly associated with stunting among slum
      children as revealed in multiple regression analysis. Thus, a multipronged
      approach is needed such as giving priority to improve education for slum
      community especially for women, creating awareness regarding benefits of early
      initiation of breastfeeding, small family size, and proper storage of drinking
      water, and providing toilet facility in slum households which could improve the
      nutritional status of slum children.

PMID- 25580462
TI  - Nanospray drying as a novel technique for the manufacturing of inhalable NSAID
      powders.
AB  - The aim of this research was to evaluate the potential of the nanospray drier as
      a novel apparatus for the manufacturing of a dry powder for inhalation containing
      ketoprofen lysinate, a nonsteroidal anti-inflammatory drug able to control the
      inflammation in cystic fibrosis patients. We produced several ketoprofen lysinate
      and leucine powder batches by means of nanospray dryer, studying the influence of
      process parameters on yield, particle properties (size distribution and
      morphology), and, mainly, aerodynamic properties of powders. Micronized particles
      were prepared from different hydroalcoholic solutions (alcohol content from 0 to
      30% v/v) using ketoprofen in its lysine salt form and leucine as dispersibility
      enhancer in different ratios (from 5 to 15% w/w) with a total solid concentration
      ranging from 1 to 7% w/v. Results indicated that the spray head equipped with a 7
      um nozzle produced powders too big to be inhaled. The reduction of nozzle size
      from 7 to 4 um led to smaller particles suitable for inhalation but, at the same
      time, caused a dramatic increase in process time. The selection of process
      variables, together with the nozzle pretreatment with a surfactant solution,
      allowed us to obtain a free flowing powder with satisfying aerosol performance,
      confirming the usefulness of the nanospray drier in the production of powder for
      inhalation.

PMID- 25580461
TI  - HIV treatment as prevention: contradictory perspectives from dynamic mathematical
      models.
AB  - The preventative effects of antiretroviral therapy for people with HIV have been
      debated since they were first raised. Models commenced studying the preventive
      effects of treatment in the 1990s, prior to initial public reports. However, the
      outcomes of the preventive effects of antiretroviral use were not consistent.
      Some outcomes of dynamic models were based on unfeasible assumptions, such as no
      consideration of drug resistance, behavior disinhibition, or economic inputs in
      poor countries, and unrealistic input variables, for example, overstated
      initiation time, adherence, coverage, and efficacy of treatment. This paper
      reviewed dynamic mathematical models to ascertain the complex effects of ART on
      HIV transmission. This review discusses more conservative inputs and outcomes
      relative to antiretroviral use in HIV infections in dynamic mathematical models.
      ART alone cannot eliminate HIV transmission.

PMID- 25580463
TI  - Pyruvic oxime nitrification and copper and nickel resistance by a Cupriavidus
      pauculus, an active heterotrophic nitrifier-denitrifier.
AB  - Heterotrophic nitrifiers synthesize nitrogenous gasses when nitrifying ammonium
      ion. A Cupriavidus pauculus, previously thought an Alcaligenes sp. and noted as
      an active heterotrophic nitrifier-denitrifier, was examined for its ability to
      produce nitrogen gas (N2) and nitrous oxide (N2O) while heterotrophically
      nitrifying the organic substrate pyruvic oxime [CH3-C(NOH)-COOH]. Neither N2 nor
      N2O were produced. Nucleotide and phylogenetic analyses indicated that the
      organism is a member of a genus (Cupriavidus) known for its resistance to metals
      and its metabolism of xenobiotics. The microbe (a Cupriavidus pauculus designated
      as C. pauculus strain UM1) was examined for its ability to perform heterotrophic
      nitrification in the presence of Cu(2+) and Ni(2+) and to metabolize the
      xenobiotic phenol. The bacterium heterotrophically nitrified well when either 1
      mM Cu(2+) or 0.5 mM Ni(2+) was present in either enriched or minimal medium. The
      organism also used phenol as a sole carbon source in either the presence or
      absence of 1 mM Cu(2+) or 0.5 mM Ni(2+). The ability of this isolate to perform a
      number of different metabolisms, its noteworthy resistance to copper and nickel,
      and its potential use as a bioremediation agent are discussed.

PMID- 25580464
TI  - Screening of trace elements in hair of the female population with different types
      of cancers in Wielkopolska region of Poland.
AB  - BACKGROUND: Cancer constitutes a major health problem worldwide. Thus, search for
      reliable and practical markers of the disease process remains the key issue of
      the diagnostic process. OBJECTIVES: The study aims at linking the trace element
      status of an organism, assessed by hair analysis, with the occurrence of cancer
      diseases. MATERIAL AND METHODS: Hair samples were collected from 299 patients
      with cancer diseases confirmed by a histopathological test and from 100 controls.
      Cancer patients were divided into three groups, depending on cancer type: hormone
      dependent cancer, cancer of the alimentary tract, and cancer with high glycolytic
      activity. Mineral element analysis of hair was performed using an atomic emission
      spectrophotometer with inductively coupled plasma (ICP-OES) and inductively
      coupled plasma mass spectrometry (ICP-MS). RESULTS: Statistically significantly
      lower concentrations of selenium, zinc, copper, germanium and boron, iron, and
      magnesium were observed in the three groups of cancer patients. Disturbance in
      the axis glucose-insulin and changes in concentrations of heavy metals and toxic
      elements were also noted. CONCLUSIONS: It seems safe to conclude that our results
      confirmed usefulness of hair element analysis in screening tests for the
      assessment of the biomarker of various cancer diseases in a female population.

PMID- 25580465
TI  - Increased ER stress as a mechanism of retinal neurovasculopathy in mice with
      severe hyperhomocysteinemia.
AB  - Hyperhomocysteinemia is implicated in retinal neurovascular diseases including
      arterial occlusive disease, venous occlusive disease and pseudoexfoliation
      glaucoma. The mechanism for these diseases is not known. Here we used
      hyperhomocysteinemic mice lacking the gene encoding cystathionine-beta-synthase
      (cbs-/-) to examine whether ER stress could be a mechanism for the retinal
      neurovasculopathy reported in these mice. Retinas of cbs+/+ and cbs-/- mice (age:
      3-5 wks) were used to investigate the expression of ER stress genes (BiP/GRP78,
      Perk, Atf6, Atf4, Ire1alpha, Chop) and the proteins they encode. The levels of
      poly(ADP-ribose) polymerase (PARP) and cleaved cysteine-aspartic proteases-3
      (caspase-3), proteins known to be involved in apoptosis, were also examined.
      Quantitative reverse transcription polymerase chain reaction and western blotting
      revealed an increase in BiP/GRP78 and PERK in retinas of cbs-/- mice compared
      with cbs+/+ mice. There was an elevation of CCAAT-enhancer-binding protein
      homologous protein (CHOP) in retinal cryosections of cbs-/- mice indicating
      apoptosis, which was confirmed by increased levels of PARP and cleaved caspase-3.
      The data suggest that the genes and proteins that are major players in the ER
      stress pathway, particularly the PERK pathway, are upregulated in retinas of cbs
      /- mice. The data support a role for ER stress in the pathophysiology associated
      with the hyperhomocysteinemia-linked retinal disease.

PMID- 25580466
TI  - [A couple-based approach: An innovative effort to tackle HIV infection among
      Latino gay men.]
AB  - The HIV epidemic is a serious and pervasive health issue in the Latino community.
      While prevention efforts have helped maintain stability in the overall number of
      infections among Latinos for more than a decade, this population continues to be
      affected by HIV at high levels. In particular, Predominantly Spanish-speaking
      Latino men who have sex with men (MSM) are disproportionately impacted by HIV.
      Several factors contribute to the HIV epidemic among Predominantly Spanish
      speaking Latino MSM including substance use; intimate partner violence; the
      presence of certain STIs; same-sex relationship dynamics; avoidance of seeking
      testing counseling and treatment out of fear of discrimination and immigration
      status; and poverty, migration patterns, and language barriers. In particular,
      epidemiological behavioral research has identified how relationship dynamics in
      male couples are associated with sexual risk behavior. Consequently, further
      research is needed to identify and deliver interventions geared toward couple
      based risk reduction among men in same-sex relationships. This paper describes
      the potential significance that innovative couple-based approaches can have on
      reducing HIV and AIDS cases among Predominantly Spanish-speaking Latino MSM and
      their same-sex partners.

PMID- 25580467
TI  - Traumatic Brain Injury Causes a Tacrolimus-Sensitive Increase in Non-Convulsive
      Seizures in a Rat Model of Post-Traumatic Epilepsy.
AB  - Epilepsy is a significant but potentially preventable complication of traumatic
      brain injury (TBI). Previous research in animal models of acquired epilepsy has
      implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab
      recently found that calcineurin activity in the rat hippocampus increases acutely
      after lateral TBI. Here we use a calcineurin inhibitor test whether an acute
      increase in calcineurin activity is necessary for the development of late post
      traumatic seizures. Adult rats were administered the calcineurin inhibitor
      Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then
      monitored by video-electrocorticography (video-ECoG) for spontaneous seizure
      activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform
      activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks
      post-TBI though, nearly all injured rats exhibited spontaneous seizures,
      including convulsive seizures which were infrequent but lasted minutes (18% of
      injured rats), and non-convulsive seizures which were frequent but lasted tens of
      seconds (94% of injured rats). We also identified non-convulsive seizures in a
      smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic
      seizures described in other rats strains. Non-convulsive seizures in the brain
      injured rats, however, were four-times more frequent and two-times longer lasting
      than in their uninjured littermates. Interestingly, rats administered Tacrolimus
      acutely after TBI showed significantly fewer non-convulsive seizures than
      untreated rats, but a similar degree of cortical atrophy. The data thus indicate
      that administration of Tacrolimus acutely after TBI suppressed non-convulsive
      seizures months later.

PMID- 25580469
TI  - Older Adults are Highly Responsive to Recent Events During Decision-Making.
AB  - Recent work suggests that older adults' decision-making behavior is highly
      affected by recent events. In the present work younger and older adults performed
      a two-choice task where one option provided a larger average reward, but there
      was a large amount of noise around the mean reward for each option which led to
      sharp improvements or declines in rewards over trials. Older adults showed
      greater responsiveness to recent events than younger adults as evidenced by fits
      of Reinforcement Learning (RL) models. Older adults were particularly sensitive
      to recent negative events, which was evidenced by a strong tendency for older
      adults to switch to the other option following steep declines in reward. This
      tendency led to superior performance for older adults in one condition where
      heightened sensitivity to recent negative events was advantageous. These results
      extend prior work that has found an older adult bias toward negative feedback,
      and suggest that older adults engage in more abrupt switching in response to
      negative outcomes than younger adults.

PMID- 25580468
TI  - A pilot phase II Study of digoxin in patients with recurrent prostate cancer as
      evident by a rising PSA.
AB  - BACKGROUND: Digoxin was found to inhibit prostate cancer (PCa) growth via the
      inhibition of HIF-1alpha synthesis in a mouse model. We hypothesized that a
      therapeutic dose of digoxin could inhibit human PCa growth and disease
      progression. METHODS: An open label, single arm pilot study was performed.
      Patients (pts) with non-metastatic, biochemically relapsed PCa with prostate
      specific antigen doubling time (PSADT) of 3-24 months and no hormonal therapy
      within the past 6 months were enrolled. All pts had testosterone > 50 ng/dL at
      baseline. Digoxin was taken daily with dose titration to achieve a target
      therapeutic level (0.8 - 2 ng/ml); patients had routine follow-up including
      cardiac monitoring with 12-lead electrocardiograms (ECGs) and digoxin levels. The
      primary endpoint was the proportion of pts at 6 months post-treatment with a
      PSADT >= 200% from the baseline. HIF-1alpha downstream molecule vascular
      endothelial growth factor (VEGF) was measured in plasma. RESULTS: Sixteen pts
      were enrolled and 14 pts finished the planned 6 months of treatment. Twenty
      percent (3/15) of the pts had PSA decrease >25% from baseline with a medium
      duration of 14 months. At 6 months, 5 of 13 (38%) pts had PSADT >= 200% of the
      baseline PSADT and were continued on study for an additional 24 weeks of
      treatment. Two patients had durable PSA response for more than 1 year. Digoxin
      was well tolerated with possible relation of one grade 3 back pain. No patients
      had evidence of digoxin toxicity. The digoxin dose was lowered in 2 patients for
      significant ECGs changes (sinus bradycardia and QT prolongation), and there were
      probable digoxin-related ECG changes in 3 patients. Plasma VEGF was detected in 4
      (25%) patients. CONCLUSIONS: Digoxin was well tolerated and showed a prolongation
      of PSDAT in 38% of the patients. However, there was no significant difference
      comparing that of similar patients on placebo from historical data. Digoxin at
      the dose used in this study may have limited benefit for patients with
      biochemically relapsed prostate cancer.

PMID- 25580470
TI  - Orientation Refinement of Virus Structures with Unknown Symmetry.
AB  - Structural biology, in particular the structure determination of viruses and
      other large macromolecular complexes leads to data- and compute-intensive
      problems that require resources well beyond those available on a single system.
      Thus, there is an imperative need to develop parallel algorithms and programs for
      clusters and computational grids. We present one of the most challenging
      computational problems posed by the three-dimensional structure determination of
      viruses, the orientation refinement.

PMID- 25580471
TI  - Privacy-Preserving Publication of Diagnosis Codes for Effective Biomedical
      Analysis.
AB  - Patient-specific records contained in Electronic Medical Record (EMR) systems are
      increasingly combined with genomic sequences and deposited into bio-repositories.
      This allows researchers to perform large-scale, low-cost biomedical studies, such
      as Genome-Wide Association Studies (GWAS) aimed at identifying associations
      between genetic factors and complex health-related phenomena, which are an
      integral facet of personalized medicine. Disseminating this data, however, raises
      serious privacy concerns because patients' genomic sequences can be linked to
      their identities through diagnosis codes. This work proposes an approach that
      guards against this type of data linkage by modifying diagnosis codes in a way
      that limits the probability of associating a patient's identity to their genomic
      sequence. Experiments using EMRs from the Vanderbilt University Medical Center
      verify that our approach generates data that can support up to 29.4% more GWAS
      than the best-so-far method, while permitting biomedical analysis tasks several
      orders of magnitude more accurately.

PMID- 25580472
TI  - Predicting the severity of motor neuron disease progression using electronic
      health record data with a cloud computing Big Data approach.
AB  - Motor neuron diseases (MNDs) are a class of progressive neurological diseases
      that damage the motor neurons. An accurate diagnosis is important for the
      treatment of patients with MNDs because there is no standard cure for the MNDs.
      However, the rates of false positive and false negative diagnoses are still very
      high in this class of diseases. In the case of Amyotrophic Lateral Sclerosis
      (ALS), current estimates indicate 10% of diagnoses are false-positives, while 44%
      appear to be false negatives. In this study, we developed a new methodology to
      profile specific medical information from patient medical records for predicting
      the progression of motor neuron diseases. We implemented a system using Hbase and
      the Random forest classifier of Apache Mahout to profile medical records provided
      by the Pooled Resource Open-Access ALS Clinical Trials Database (PRO-ACT) site,
      and we achieved 66% accuracy in the prediction of ALS progress.

PMID- 25580473
TI  - Enhancing Patient Adherence: Promoting Engagement via Positive Patient-Provider
      Relationships in HIV/AIDS Care.
AB  - The face of HIV/AIDS has shifted. Traditionally disenfranchised groups including
      African Americans and those known to be current or past substance-users are
      disproportionately infected and affected by the domestic HIV/AIDS epidemic. While
      caring for all people living with HIV/AIDS (PLWHA) is a public health priority,
      there are vast disparities in HIV/AIDS care and outcomes linked to treatment
      engagement and medication adherence. Historically, providers and researchers have
      focused heavily on seeking effective interventions to promote medication
      adherence among patients engaged in care. After having modest success when
      concentrating solely on outcomes pertaining to medication adherence (i.e.,
      medication taking), the definition of adherence is broadening. Adherence to
      medications is now thought to occur along a continuum of engagement in care with
      regard to chronic illnesses such as HIV/AIDS. Patient-provider communication
      styles that are consistent with a motivational interviewing (MI) style are useful
      in enhancing active engagement in care, with potential to promote better
      medication adherence. Positive patient-provider relationships may be conduits for
      positive changes in vulnerable patients' lives. Positive changes in individual
      patients' lives culminate to reduce disparities in health status between PLWHA on
      a population level.

PMID- 25580474
TI  - Listening to Consumer Perspectives to Inform Addictions and Housing-Related
      Practice and Research.
AB  - The study, funded by the Northwest Health Foundation of Portland, Oregon and the
      National Institute on Drug Abuse (NIDA), was conducted as part of the HEARTH
      collaborative (Housing, Employment and Recovery Together for Health). HEARTH,
      established in 2010, is a community-academic partnership involving partners from
      Portland State University (PSU), Oregon Health and Science University (OHSU), and
      Central City Concern (CCC). Using the approaches of community-based participatory
      research (CBPR), these diverse stakeholders collaborated to co-develop research
      of direct relevance to the local community and to national academic and policy
      communities. This study employed qualitative methods and community-based
      participatory research principles to solicit personal experiences with housing,
      employment, and recovery programs. We recruited interview participants via CCC
      operated housing programs, including Alcohol and Drug Free Community Housing
      (ADFC), family housing, transitional housing, and non-ADFC (low barrier) housing
      units. The manuscript presents interview themes based on the five broad
      categories of interview questions: housing, employment programs, recovery
      programs, definitions of recovery, and definitions of success. Co-authors
      describe recommendations for practice and research protocol based on our
      findings. Our results highlight the importance of involving consumers in the
      development, data collection, and analysis of research, and present the unique
      perspectives of those who experience homelessness, recovery, and the programs
      designed to assist them.

PMID- 25580475
TI  - Computer-Aided Detection of Colorectal Lesions with Super-Resolution CT
      Colonography: Pilot Evaluation.
AB  - Reliable computer-aided detection (CADe) of small polyps and flat lesions is
      limited by the relatively low image resolution of computed tomographic
      colonography (CTC). We developed a sinogram-based super-resolution (SR) method to
      enhance the images of lesion candidates detected by CADe. First, CADe is used to
      detect lesion candidates at high sensitivity from conventional CTC images. Next,
      the signal patterns of the lesion candidates are enhanced in sinogram domain by
      use of non-uniform compressive sampling and iterative reconstruction to produce
      SR images of the lesion candidates. For pilot evaluation, an anthropomorphic
      phantom including simulated lesions was filled partially with fecal tagging and
      scanned by use of a CT scanner. A fully automated CADe scheme was used to detect
      lesion candidates in the images reconstructed at conventional 0.61-mm and at 0.10
      mm SR image resolution. The proof-of-concept results indicate that the SR method
      has potential to reduce the number of FP CADe detections below that obtainable
      with the conventional CTC imaging technology.

PMID- 25580476
TI  - Enamel and dentin bond strength, interfacial ultramorphology and fluoride ion
      release of self-etching adhesives during a pH-cycling regime.
AB  - PURPOSE: This study evaluated the effects of pH cycling on fluoride release and
      bond strength of two self-etching adhesive systems to both enamel and dentin. The
      ultramorphology of the interfaces produced by the adhesive systems were also
      analyzed. MATERIALS AND METHODS: The buccal surfaces of bovine incisors were
      flattened to expose enamel and dentin, which were bonded with either Clearfil
      Protect Bond (CPB) or One-Up Bond F Plus (OBP). The bonded samples were prepared
      for microtensile bond strength (MUTBS) testing, fluoride ion release, and
      transmission electron microscopy. pH cycling comprised demineralization (8 h/day)
      and remineralization (16 h/day) cycles for 8 days. The MUTBS data were analyzed
      by two-way ANOVA, while fluoride release was analyzed using the Friedman and
      Wilcoxon tests. RESULTS: The adhesives presented similar bond strengths to
      enamel. However, the dentin bond strength of CPB was higher than that of OBP. pH
      cycling did not influence enamel or dentin MUTBS. The amount of fluoride released
      from the bonded enamel and dentin was low and varied among the groups. The
      morphological evaluation showed that the thickness of the dentin hybrid layers
      was similar for both adhesives. CONCLUSION: The pH-cycling regime did not affect
      enamel or dentin bond strengths. In enamel, both the self-etching adhesives
      tested presented similar bond strengths, but in dentin, Clearfil Protect Bond
      showed higher dentin bonding than One-Up Bond F Plus.

PMID- 25580477
TI  - A turn-on fluorescent probe for hypochlorous acid based on the oxidation of
      diphenyl telluride.
AB  - A fluorescent probe HCTe was developed for rapid detection of hypochlorous acid
      based on the specific HOCl-promoted oxidation of diphenyl telluride. The reaction
      is accompanied by an 82-fold increase in the fluorescence quantum yield (from
      0.009 to 0.75). The fluorescence turn-on mechanism is achieved by the suppression
      of photoinduced electron transfer (PET) from the diphenyl telluride group to
      BODIPY. The fluorescence intensity of the reaction between HOCl and HCTe is
      linear in the HOCl concentration range of 1 to 10 MUM with a detection limit of
      41.3 nM (S/N = 3). In addition, confocal fluorescence microscopy imaging using
      RAW264.7 macrophages demonstrated that HCTe could be an efficient fluorescent
      probe for HOCl detection in living cells. 

PMID- 25580478
TI  - Multi-site cyclization via initial C-H activation using a rhodium(III) catalyst:
      rapid assembly of frameworks containing indoles and indolines.
AB  - Tandem multi-site cyclization triggered by Rh(iii)-catalyzed C-H activation has
      been achieved for highly efficient synthesis of spirocycle indolin-3-one (C2
      cyclization), benzo[a]carbazole (C3-cyclization) and an unusual indoxyl core (N1
      cyclization). In particular, the synthesis of pseudo-indoxyl is typically
      completed within 10 min, and the reaction tolerates air, water and a range of
      solvents. 

PMID- 25580479
TI  - Dependence of crystal size on the catalytic performance of a porous coordination
      polymer.
AB  - Submicrosized MOF-76(Yb) exhibits a higher catalytic performance for
      esterification than microsized MOF-76(Yb). Control of the crystal size of porous
      heterogeneous catalysts, such as PCP/MOFs, offers a promising approach to
      fabricating high-performance catalysts based on accessibility to the internal
      catalytic sites. 

PMID- 25580480
TI  - Molecular biomarkers of phospholipidosis in rat  blood and heart after amiodarone
      treatment.
AB  - Phospholipidosis (PLD) is characterized by an intracellular accumulation of
      phospholipids in lysosomes and concurrent development of concentric lamellar
      bodies. It is induced in humans and in animals by drugs with a cationic
      amphiphilic structure. The purpose of the present study was to identify a set of
      molecular biomarkers of PLD in rat blood and heart, hypotheticallya pplicable in
      preclinical screens within the drug development process. A toxicological study
      was set up in rats orally treated up to 11 days with 300 mg kg(-1) per day(-1)
      amiodarone (AMD). Light and transmission electron microscopy investigations were
      performed to confirm the presence of lamellar bodies indicative of phospholipid
      accumulation. The effects of AMD upon the transcriptome of these tissues were
      estimated using DNA microarray technology. Microarray data analysis showed that a
      total of 545 and 8218 genes were modulated by AMD treatment in heart and blood,
      respectively. Some genes implicated in the phospholipid accumulation in cells,
      such as phospholipase A2, showed similar alterations of gene expression. After
      transcriptome criteria of analysis and target selection, including also the
      involvement in the onset of PLD, 7 genes (Pla2g2a, Pla2g7, Gal, Il1b, Cebpb,
      Fcgr2b, Acer 2) were selected as candidate biomarkers of PLD in heart and blood
      tissues, and their potential usefulness as a sensitive screening test was
      screened and confirmed by quantitative Real-Time PCR analysis. Collectively,
      these data underscore the importance of transcriptional profiling in drug
      discovery and development, and suggest blood as a surrogate tissue for possible
      phospholipid accumulation in cardiomyocytes.

PMID- 25580481
TI  - Fish multigeneration test with preliminary  short-term reproduction assay for
      estrone  using Japanese medaka (Oryzias latipes).
AB  - The most potent chemicals potentially causing adverse effects on fish species are
      estrogens in human waste.Sewage is a source of these estrogens and it is
      difficult to reduce. In particular, although the bioactivity of estrone is
      estimated to be about half of that of estradiol, multiple studies report that
      more than 100 ng l(-1) of estrone can be detected in urban rivers, including
      discharges from sewage treatment works; approximately two times as high as
      estradiol. Few studies have been conducted to investigate the long-term effects
      of estrone on wildlife; therefore, we conducted fish multigeneration test using
      Japanese medaka (Oryzias latipes). Medaka were exposed to estrone for 27 weeks
      across three generations in environmentally relevant concentrations, being 5.74,
      11.4, 24.0, 47.1 and 91.4 ng l(-1). No effects on reproduction were observed in
      the first generation; however, a decline in egg production and fertility was
      observed in the second generation exposed to 91.4 ng l(-1) estrone, which is
      lower than some known environmental concentrations in urban environments.
      Furthermore, histopathological abnormalities were observed in the third
      generation exposed to both 47.1 and 91.4 ng l(-1), suggesting that estrone
      possibly exerts severe effects on the third or later generations. However,
      appearances of testis-ova were observed in the second and third generation they
      were not consistent with actual effects on reproduction, notwithstanding the
      testis-ovais regarded as the key evidence for endocrine disruption. Accordingly,
      we consider that qualitative measurement of abnormalities using histopathological
      observations is required for appropriate evaluation of endocrine disruption.

PMID- 25580482
TI  - Growth evaluation method by live imaging of  Daphnia magna and its application to
      the  estimation of an insect growth regulator.
AB  - The zooplankton Daphnia magna has been widely used as a test organism to assess
      the toxicity of chemical substances because of its important position in aquatic
      ecology and its ease of handling. Among the various endpoints for toxicity
      evaluation, growth rate is one of the most critical and many studies have been
      conducted. However, measurement f growth rate was time-consuming and not an ideal
      endpoint in terms of screening. In this study, we demonstrated a live imaging
      method to monitor the growth of daphnids by area measurement. In this method,
      daphnid images were directly obtained from a swimming chamber and these images
      were processed for the evaluation of growth. The reliability of this method was
      confirmed by comparison with the conventional dry weight method of the same
      animals. The body area of daphnids using this method showed a strong correlation
      with the dry weight method, with R(2) = 0.930. In addition, we quantified the
      effect of a toxicant, fenoxycarb, on the growth of the animal. Fenoxycarb
      concentrations of 0, 0.027,0.27 and 2.7 MUg l(-1) were tested and their effects
      on growth were estimated by the live imaging method. In the toxicity test,the
      area of daphnids decreased significantly with increasing fenoxycarb
      concentration. These results indicate that the present live imaging method is a
      reliable approach for daphnid toxicity testing. This method is promising for high
      through put Daphnia toxicity tests and real-time individual observations.

PMID- 25580484
TI  - The latest on PaxVax' and Gotovax AB's cholera vaccine candidates.

PMID- 25580483
TI  - Agenus' genital herpes vaccine significantly reduces viral burden in Phase 2.

PMID- 25580485
TI  - ACIP ponders recommendation for Prevnar use in seniors.

PMID- 25580486
TI  - Cytological aspects of an ovarian sex cord tumour with annular tubules.

PMID- 25580487
TI  - Is there a species spectrum within the world-wide leaf economics spectrum? Major
      variations in leaf functional traits in the Mediterranean sclerophyll Quercus
      ilex.
AB  - The leaf economics spectrum is a general concept describing coordinated variation
      in foliage structural, chemical and physiological traits across resource
      gradients. Yet, within this concept,the role of within-species variation,
      including ecotypic and plastic variation components, has been largely neglected.
      This study hypothesized that there is a within-species economics spectrum within
      the general spectrum in the evergreen sclerophyll Quercus ilex which dominates
      low resource ecosystems over an exceptionally wide range. An extensive database
      of foliage traits covering the full species range was constructed, and improved
      filtering algorithms were developed. Standardized data filtering was deemed
      absolutely essential as additional variation sources can result in trait
      variation of 10-300%,blurring the broad relationships. Strong trait variation, c.
      two-fold for most traits to up to almost an order of magnitude, was
      uncovered.Although the Q. ilex spectrum is part of the general spectrum, within
      species trait and climatic relationships in this species partly differed from the
      overall spectrum. Contrary to world-wide trends, Q. ilex does not necessarily
      have a low nitrogen content per mass and can increase photosynthetic capacity
      with increasing foliage robustness. This study argues that the within-species
      economics spectrum needs to be considered in regional- to biome-level analyses.

PMID- 25580488
TI  - Motives for adherence to a gluten-free diet: a qualitative   investigation
      involving adults with coeliac disease.
AB  - BACKGROUND: Currently , the only treatment for coeliac disease is life long
      adherence to a strict gluten-free diet. Strict adherence to a gluten-free diet is
      challenging, with recent reports suggesting that adherence rates range from 42%
      to 91%. The present study aimed to: (i) identify motives for adhering to a gluten
      free diet and (ii) explore factors implicated in adherence and non-adherence
      behaviour in terms of accidental and purposeful gluten consumption among adults
      with coeliac disease. METHODS: Two hundred and three adults with coeliac disease
      completed an online questionnaire. Using a qualitative design, relationships were
      examined between reported adherence and motivation to follow a gluten-free diet,
      as well as the onset, duration and severity of symptoms. RESULTS: Feelings of
      desperation ('hitting rock bottom') and needing to gain or lose weight were
      associated with the strictest adherence to a gluten-free diet. Participants who
      accidentally consumed gluten over the past week developed symptoms the most
      quickly and reported the most pain over the past 6 months. Participants who
      consumed gluten on purpose over the past week reported a shorter duration of
      symptoms and less pain over the past 6 months. CONCLUSIONS: Hitting rock bottom
      and needing to gain or lose weight were factors associated with the strictest
      adherence, when considered in the context of both accidental and purposeful
      gluten consumption. Future research is warranted to develop resources to help
      people with coeliac disease follow a strict gluten-free diet.

PMID- 25580489
TI  - [RCN, Rare Cancer Network].

PMID- 25580490
TI  - [Anemia in pregnancy].

PMID- 25580491
TI  - [Mercury poisoning in a newborn].

PMID- 25580492
TI  - [Homage to Alain Bernheim].

PMID- 25580493
TI  - [A humid climate is favorable for Penicillium marneffei infestation].

PMID- 25580495
TI  - [Snake bites].

PMID- 25580494
TI  - [Treatment of lymphatic filariasis by a double dose].

PMID- 25580496
TI  - [Penile fractures].

PMID- 25580498
TI  - [Cancer and HIV].

PMID- 25580499
TI  - [The ex-vivo culture of circulating tumor cells: a real hope for personalized
      therapy?].

PMID- 25580500
TI  - [NSAID use reduces the risk of breast cancer recurrence in overweight and obese
      women].

PMID- 25580501
TI  - [The 2014 Georges Mathe award rewards a research project on the role of the
      immune system in the success of anti-cancer therapy].

PMID- 25580502
TI  - FISH: negative. Morphology: positive.

PMID- 25580503
TI  - Editorial: Bringing regenerative medicine therapies to the 21st century.

PMID- 25580504
TI  - Predictive testing and Alzheimer disease.

PMID- 25580505
TI  - Diagnostics in the front line against infectious disease.

PMID- 25580507
TI  - An unusual cause for chronic right-sided abdominal pain: question.

PMID- 25580506
TI  - Management of angioedema without urticaria in the emergency  department.
AB  - Angioedema refers to a localized, transient swelling of the deep skin layers or
      the upper respiratory or gastrointestinal mucosa. It develops as a result of
      mainly two different vasoactive peptides, histamine or bradykinin.
      Pathophysiology, as well as treatment, is different in each case; nevertheless,
      the resulting signs and symptoms may be similar and difficult to distinguish.
      Angioedema may occur at any location. When the affected area involves the upper
      respiratory tract, both forms of angioedema can lead to an imminent upper airway
      obstruction and a life-threatening emergency. Emergency physicians must have a
      basic understanding of the pathophysiology underlying this process. Angioedema
      evaluation in the emergency department (ED) should aim to distinguish between
      histamine- and bradykinin-induced angioedema, in order to provide appropriate
      treatment to patients. However, diagnostic methods are not available at the ED
      setting, neither to confirm one mechanism or the other, nor to identify a cause.
      For this reason, the management of angioedema should rely on clinical data
      depending on the particular features of the episode and the patient in each case.
      The history-taking should be addressed to identify a possible etiology or
      triggering agent, recording complete information for an ulterior diagnostic study
      in the outpatient clinic. It is mandatory quickly to recognize and treat a
      potential life-threatening upper airway obstruction or anaphylaxis. This review
      focuses on the underlying mechanisms and management of histamine- and bradykinin
      induced angioedema at the emergency department and provides an update on the
      currently available treatments.

PMID- 25580508
TI  - A 67-year-old man with painful diplopia: question.

PMID- 25580510
TI  - Theoretical study of singlet oxygen molecule generation via an exciplex with
      valence-excited thiophene.
AB  - Singlet-oxygen [O2((1)Deltag)] generation by valence-excited thiophene (TPH) has
      been investigated using multireference Moller-Plesset second-order perturbation
      (MRMP2) theory of geometries optimized at the complete active space self
      consistent field (CASSCF) theory level. Our results indicate that triplet
      TPH(1(3)B2) is produced via photoinduced singlet TPH(2(1)A1) because 2(1)A1 TPH
      shows a large spin-orbit coupling constant with the first triplet excited state
      (1(3)B2). The relaxed TPH in the 1(3)B2 state can form an exciplex with
      O2((3)Sigmag(-)) because this exciplex is energetically more stable than the
      relaxed TPH. The formation of the TPH(1(3)B2) exciplex with O2((3)Sigmag(-))
      whose total spin multiplicity is triplet (T1 state) increases the likelihood of
      transition from the T1 state to the singlet ground or first excited singlet
      state. After the transition, O2((1)Deltag) is emitted easily although the
      favorable product is that from a 2 + 4 cycloaddition reaction. 

PMID- 25580509
TI  - Nickel superoxide dismutase: structural and functional roles of His1 and its H
      bonding network.
AB  - Crystal structures of nickel-dependent superoxide dismutases (NiSODs) reveal the
      presence of a H-bonding network formed between the NH group of the apical
      imidazole ligand from His1 and the Glu17 carboxylate from a neighboring subunit
      in the hexameric enzyme. This interaction is supported by another intrasubunit H
      bond between Glu17 and Arg47. In this study, four mutant NiSOD proteins were
      produced to experimentally evaluate the roles of this H-bonding network and
      compare the results with prior predictions from density functional theory
      calculations. The X-ray crystal structure of H1A-NiSOD, which lacks the apical
      ligand entirely, reveals that in the absence of the Glu17-His1 H-bond, the active
      site is disordered. Characterization of this variant using X-ray absorption
      spectroscopy (XAS) shows that Ni(II) is bound in the expected N2S2 planar
      coordination site. Despite these structural perturbations, the H1A-NiSOD variant
      retains 4% of wild-type (WT) NiSOD activity. Three other mutations were designed
      to preserve the apical imidazole ligand but perturb the H-bonding network: R47A
      NiSOD, which lacks the intramolecular H-bonding interaction; E17R/R47A-NiSOD,
      which retains the intramolecular H-bond but lacks the intermolecular Glu17-His1 H
      bond; and E17A/R47A-NiSOD, which lacks both H-bonding interactions. These
      variants were characterized by a combination of techniques, including XAS to
      probe the nickel site structure, kinetic studies employing pulse-radiolytic
      production of superoxide, and electron paramagnetic resonance to assess the Ni
      redox activity. The results indicate that in addition to the roles in redox
      tuning suggested on the basis of previous computational studies, the Glu17-His1 H
      bond plays an important structural role in the proper folding of the "Ni-hook"
      motif that is a critical feature of the active site. 

PMID- 25580511
TI  - Denervation of the infraspinatus and release of the posterior deltoid muscles in
      the management of dyskinetic external shoulder rotation in cerebral palsy.
AB  - OBJECT: The dyskinetic subtype of cerebral palsy is difficult to manage, and
      there is no established gold standard for treatment. External rotation of the
      shoulder(s) is often managed nonsurgically using injections of botulinum toxin A
      into the external rotator muscles. This article reports a new surgical technique
      for managing external rotation when botulinum toxin A treatment is not sufficient
      or possible. METHODS: Six patients with dyskinetic cerebral palsy underwent
      denervation of the infraspinatus muscle and release of the posterior part of the
      deltoid muscle. Postoperative questionnaires were given to the
      patients/caregivers, and video recordings were made both pre- and
      postoperatively. Preoperative and postoperative Assisting Hand Assessment was
      possible in only 1 case. RESULTS: Five patients were very satisfied with their
      outcome. Four patients' video recordings showed improvement in their condition.
      One patient developed postoperative complications. CONCLUSIONS: The results
      indicate that denervation of the infraspinatus muscle and posterior deltoid
      release can be an option for patients with dyskinetic cerebral palsy to manage
      external rotation of the shoulder when other treatment alternatives are
      insufficient.

PMID- 25580512
TI  - Does the real-time thermal damage estimate allow for estimation of tumor control
      after MRI-guided laser-induced thermal therapy? Initial experience with recurrent
      intracranial ependymomas.
AB  - OBJECT Although control of intracranial ependymomas is highly correlated with
      degree of resection, it is unknown if the same is true for MRI-guided laser
      induced thermal therapy (MRgLITT). The authors report their experience with
      MRgLITT for ependymoma and examine the utility of the real-time thermal damage
      estimate (TDE), a recent software advance, with respect to completeness of
      ablation and impact on tumor control. To the authors' knowledge, this is the
      largest single-center experience utilizing MRgLITT for recurrent ependymomas.
      METHODS Five tumors in 4 patients were treated with the Visualase Thermal Therapy
      System. Two tumors were treated similarly on recurrence. Ablation was performed
      using a 980-nm diode laser with a real-time image acquisition system. Single
      plane TDEs were calculated and compared with the original lesion area to compute
      percentage area ablated (PAA). Volumetric analysis was performed, and percentage
      volume ablated (PVA) was estimated and correlated with the TDE. Tumor control was
      correlated with the TDE and volumetric data during treatment. RESULTS Nine
      ablations were performed on 5 tumors, 2 of which had multiple recurrences. The
      average pretreatment lesion volume was 8.4 +/- 6.3 cm(3), and the average largest
      2D area was 5.3 +/- 2.7 cm(2). The averaged TDE was 3.9 +/- 2.1 cm(2), average
      PAA was 80.1% +/- 34.3%, and average PVA was 64.4% +/- 23.5%. For subtotal
      ablations, average recurrence time was 4.4 +/- 5.3 months; 1 adult case remains
      recurrence-free at 40 months. Using TDEs, the correlation between recurrence time
      and PAA was r = 0.93 (p = 0.01), and for PVA was r = 0.88 (p = 0.02).
      Furthermore, PVA and PAA were strongly correlated (r = 0.88, p = 0.02).
      CONCLUSIONS Through using the PAA, the real-time TDE correlated with the volume
      of ablation in this initial investigation. Furthermore, the TDE and volumetric
      data corresponded to the level of tumor control, with time to recurrence
      dependent on ablation completeness. MRgLITT may have a role in the management of
      recurrent ependymomas, especially with recent software advances. 

PMID- 25580513
TI  - Thirteen-year follow-up of parasellar intravascular papillary endothelial
      hyperplasia successfully treated by surgical excision: case report.
AB  - Intracranial intravascular papillary endothelial hyperplasia (IPEH) is very rare,
      and to our knowledge long-term follow-up results have not been previously
      published. An 11-year-old boy presented with a 6-month history of progressive
      visual impairment in the right eye. Magnetic resonance imaging revealed a well
      enhanced, large parasellar mass involving the cavernous sinus, right frontal
      skull base, and ethmoid and sphenoid sinuses. Frontotemporal craniotomy and
      subtotal resection were performed, and the diagnosis of IPEH was confirmed. The
      mass increased in size during the following 3 months. A second operation was
      performed via frontotemporal craniotomy combined with a transsphenoidal approach,
      and gross-total resection of the tumor was achieved. Adjuvant radiotherapy (5040
      cGy) and chemotherapy with interferon were administered. The patient's visual
      symptoms improved, and there was no recurrence during a 13-year follow-up period.
      The results of this case indicate that intracranial IPEH can recur with subtotal
      resection; however, optimal resection with multimodal adjuvant treatment can
      control the disease for many years, if not permanently. 

PMID- 25580514
TI  - Laser ablation for recurrent intracranial ependymoma.

PMID- 25580515
TI  - Novel MesoPorous BioGlass/silk scaffold containing adPDGF-B and adBMP7 for the
      repair of periodontal defects in beagle dogs.
AB  - AIM: The local delivery of growth factors via gene therapy has gained tremendous
      awareness in recent years due to their sustained growth factor delivery to target
      tissues. The aim of this study was to fabricate and investigate a scaffold able
      to release growth factors via gene therapy for the repair of periodontal tissues.
      MATERIALS AND METHODS: Novel mesoporous bioglass (MBG)/silk fibrin scaffold
      combined with BMP7 and/or PDGF-B adenovirus was fabricated and tested in vitro
      for cell migration, proliferation and differentiation. Furthermore, acute-type
      buccal dehiscence periodontal defects (mesiodistal width * depth: 5 * 5 mm) were
      created on the buccal portion of the maxillary premolars in five normal male
      beagle dogs (12 months old, 15.0 +/- 2.0 kg) and histologically examined for
      periodontal regeneration following implantation of the following five groups: (1)
      no scaffold, (2) MBG/silk scaffold alone, (3) scaffold + adPDGF-B, (4) scaffold +
      adBMP7, (5) scaffold + adPDGF-b + adBMP7. RESULTS: In vitro findings demonstrated
      that adPDGF-B was able to rapidly recruit periodontal ligament (PDL) cells over
      sixfold more effectively than adBMP7, whereas adBMP7 was more able to induce
      osteoblast differentiation of PDL cells. In vivo findings demonstrate that
      scaffolds loaded with adPDGF-B were able to partially regenerate the periodontal
      ligament while adBMP7 scaffolds primarily improved new bone formation. The
      combination of both adPDGF-B and adBMP7 synergistically promoted periodontal
      regeneration by allowing up to two times greater regeneration of the periodontal
      ligament, alveolar bone and cementum when compared to each adenovirus used alone.
      CONCLUSIONS: Although both PDGF-B and BMP7 are individually capable of promoting
      periodontal regeneration to some degree, their combination synergistically
      promotes wound healing in acute-type buccal dehiscence periodontal defects when
      delivered simultaneously. This study demonstrates the promise for successful
      delivery of low-cost, effective growth factor delivery via gene therapy for the
      treatment of periodontal defects.

PMID- 25580516
TI  - Effect of enterohaemorrhagic Escherichia coli O157:H7-specific enterohaemolysin
      on interleukin-1beta production differs between human and mouse macrophages due
      to the different sensitivity of NLRP3 activation.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection in humans can cause
      acute haemorrhagic colitis and severe haemolytic uraemic syndrome. The role of
      enterohaemolysin (Ehx) in the pathogenesis of O157:H7-mediated disease in humans
      remains undefined. Recent studies have revealed the importance of the
      inflammatory response in O157:H7 pathogenesis in humans. We previously reported
      that Ehx markedly induced interleukin-1beta (IL-1beta) production in human
      macrophages. Here, we investigated the disparity in Ehx-induced IL-1beta
      production between human and mouse macrophages and explored the underlying
      mechanism regarding the activation of NOD-like receptor family, pyrin domain
      containing 3 (NLRP3) inflammasomes. In contrast to the effects on human
      differentiated THP-1 cells and peripheral blood mononuclear cells, Ehx exerted no
      effect on IL-1beta production in mouse macrophages and splenocytes because of a
      disparity in pro-IL-1beta cleavage into mature IL-1beta upon caspase-1
      activation. Additionally, Ehx significantly contributed to O157:H7-induced ATP
      release from THP-1 cells, which was not detected in mouse macrophages. Confocal
      microscopy demonstrated that Ehx was a key inducer of cathepsin B release in THP
      1 cells but not in mouse IC-21 cells upon O157:H7 challenge. Inhibitor
      experiments indicated that O157:H7-induced IL-1beta production was largely
      dependent upon caspase-1 activation and partially dependent upon ATP signalling
      and cathepsin B release, which were both involved in NLRP3 activation. Moreover,
      inhibition of K(+) efflux drastically diminished O157:H7-induced IL-1beta
      production and cytotoxicity. The findings in this study may shed light on whether
      and how the Ehx contributes to the development of haemolytic uraemic syndrome in
      human O157:H7 infection.

PMID- 25580518
TI  - Patients' views on the availability of vegetarian medication in
      otorhinolaryngology: our experience in an eighty patient questionnaire study.

PMID- 25580517
TI  - Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is
      transported by ATB0,+, LAT1 and LAT2.
AB  - The efficacy of boron neutron capture therapy relies on the selective delivery of
      boron carriers to malignant cells. p-Boronophenylalanine (BPA), a boron delivery
      agent, has been proposed to be localized to cells through transporter-mediated
      mechanisms. In this study, we screened aromatic amino acid transporters to
      identify BPA transporters. Human aromatic amino acid transporters were
      functionally expressed in Xenopus oocytes and examined for BPA uptake and kinetic
      parameters. The roles of the transporters in BPA uptake were characterized in
      cancer cell lines. For the quantitative assessment of BPA uptake, HPLC was used
      throughout the study. Among aromatic amino acid transporters, ATB(0,+), LAT1 and
      LAT2 were found to transport BPA with Km values of 137.4 +/- 11.7, 20.3 +/- 0.8
      and 88.3 +/- 5.6 MUM, respectively. Uptake experiments in cancer cell lines
      revealed that the LAT1 protein amount was the major determinant of BPA uptake at
      100 MUM, whereas the contribution of ATB(0,+) became significant at 1000 MUM,
      accounting for 20-25% of the total BPA uptake in MCF-7 breast cancer cells.
      ATB(0,+), LAT1 and LAT2 transport BPA at affinities comparable with their
      endogenous substrates, suggesting that they could mediate effective BPA uptake in
      vivo. The high and low affinities of LAT1 and ATB(0,+), respectively,
      differentiate their roles in BPA uptake. ATB(0,+), as well as LAT1, could
      contribute significantly to the tumor accumulation of BPA at clinical dose.

PMID- 25580519
TI  - Job satisfaction and leaving intentions of midwives: analysis of a multinational
      cross-sectional survey.
AB  - AIM: To investigate the relationship between turnover intentions and job
      satisfaction among hospital midwives from seven countries and to determine how
      the related variables differ between countries. BACKGROUND: Studies investigating
      professional turnover and job satisfaction among midwives are limited in scope.
      METHOD: A cross-sectional descriptive survey was used to investigate the intended
      turnover and job satisfaction relationship among 1190 hospital midwives in
      European and Asian countries. Data were collected using a set of questionnaires
      that included questions regarding the leaving intentions of midwives and the
      McCloskey/Mueller satisfaction scale. RESULTS: Midwives were least satisfied with
      their extrinsic rewards and professional opportunities and with the balance
      between family and work. Significant differences were found in all domains of job
      satisfaction according to midwives' intentions to leave their current workplace
      in hospital or profession of midwife, and to work abroad. CONCLUSION: There are
      some general satisfying and dissatisfying elements for the profession of midwife
      across different countries. IMPLICATIONS FOR NURSING MANAGEMENT: The results
      highlight the importance of understanding midwives' leaving intentions and
      related factors across different countries. To prevent midwife turnover, health
      care managers should gain greater insight into the early stage of midwives'
      turnover intention.

PMID- 25580521
TI  - Application of the Red List Index for conservation assessment of Spanish vascular
      plants.
AB  - The International Union for Conservation of Nature (IUCN) Red List Index (RLI) is
      used to measure trends in extinction risk of species over time. The development
      of 2 red lists for Spanish vascular flora during the past decade allowed us to
      apply the IUCN RLI to vascular plants in an area belonging to a global
      biodiversity hotspot. We used the Spanish Red Lists from 2000 and 2010 to assess
      changes in level of threat at a national scale and at the subnational scales of
      Canary Islands, Balearic Islands, and peninsular Spain. We assigned retrospective
      IUCN categories of threat to 98 species included in the Spanish Red List of 2010
      but absent in the Spanish Red List of 2000. In addition, we tested the effect of
      different random and taxonomic and spatial Spanish samples on the overall RLI
      value. From 2000 to 2010, the IUCN categories of 768 species changed (10% of
      Spanish flora), mainly due to improved knowledge (63%), modifications in IUCN
      criteria (14%), and changes in threat status (12%). All measured national and
      subnational RLI values decreased during this period, indicating a general decline
      in the conservation status of the Spanish vascular flora. The Canarian RLI value
      (0.84) was the lowest, although the fastest deterioration in conservation status
      occurred on peninsular Spain (from 0.93 in 2000 to 0.92 in 2010). The RLI values
      based on subsamples of the Spanish Red List were not representative of RLI values
      for the entire country, which would discourage the use of small areas or small
      taxonomic samples to assess general trends in the endangerment of national
      biotas. The role of the RLI in monitoring of changes in biodiversity at the
      global and regional scales needs further reassessment because additional areas
      and taxa are necessary to determine whether the index is sufficiently sensitive
      for use in assessing temporal changes in species' risk of extinction.

PMID- 25580522
TI  - "I have lost everything": Trade-offs of seeking safety from intimate partner
      violence.
AB  - A primary aim of mainstream domestic violence (DV) programs is to help survivors
      and their children achieve safety from intimate partner violence. That goal,
      however, is neither simple nor straightforward. Instead, research demonstrates
      that the very actions survivors take to achieve safety may trigger a wide range
      of negative consequences. Missing from this research, however, is a focus on
      survivors' own perception, evaluation, and expectation of the costs surrounding
      their safety-seeking efforts. Using a mixed-methods design, this study explored
      safety-related trade-offs among a convenience sample of 301 female survivors
      seeking DV services across 3 states in the Northeast region of the United States.
      Quantitative findings demonstrate that 62% of participants reported having to
      give up too much to keep safe, 55% reported that safety led to new problems in
      other domains for survivors and their loved ones, and 50% reported that these
      problems were often unexpected. Qualitative findings illuminated the categories
      of loss participants experienced as they worked toward safety, as well as the
      actions participants would have taken had they anticipated these losses. Findings
      suggest that an emphasis on safety over other needs-common in a human services
      landscape composed of multiple narrowly defined service silos-can force survivors
      into a zero-sum trap of painful and detrimental trade-offs.

PMID- 25580523
TI  - Senior work-up, assessment and treatment team in the emergency department.

PMID- 25580524
TI  - Sensitization to palladium and nickel in Europe and the relationship with oral
      disease and dental alloys.
AB  - BACKGROUND: The role of palladium and nickel sensitization in oral disease and
      dermatitis is not fully understood. OBJECTIVES: To investigate whether
      sensitization to these metals was associated with exposure to dental alloys and
      oral and skin complaints/symptoms in a European multicentre study. METHODS: In
      six dermatology clinics, patch tests with palladium (3% Na2 PdCl4 ; Pd = 102.0
      umol/g) and nickel (5% NiSO4 .6H2 O; Ni = 190.2 umol/g) were performed in
      consecutive patients, and patients' characteristics were collected with a
      questionnaire and a clinical investigation. RESULTS: In total, 906 patients were
      included, of whom 24.3% reacted to palladium and 25.2% to nickel. The rate of
      monosensitization was 6-7% for both metals. Palladium sensitization (as opposed
      to no sensitization to both metals) was associated with exposure to dental crowns
      [odds ratio (OR) 2.0], skin reactivity to metals (OR 2.8), oral lichenoid lesions
      (OR 4.7), xerostomia (OR 7.3), and metal taste (OR 20.7), but not with eczema,
      stomatitis, or oral burning sensation. Additionally, xerostomia (OR 8.7) and
      metal taste (OR 4.6) were associated with sensitization to both metals.
      CONCLUSIONS: Clinically, it is important for palladium-sensitized patients to
      undergo an oral examination, with particular attention to the presence
      of/exposure to dental crowns. In the case of metal contact allergy, exposure to
      dental crowns could play a role.

PMID- 25580520
TI  - Factors associated with hepatitis C virus RNA levels in early chronic infection:
      the InC3 study.
AB  - Improved understanding of natural history of hepatitis C virus (HCV) RNA levels
      in chronic infection provides enhanced insights into immunopathogenesis of HCV
      and has implications for the clinical management of chronic HCV infection. This
      study assessed factors associated with HCV RNA levels during early chronic
      infection in a population with well-defined early chronic HCV infection. Data
      were from an international collaboration of nine prospective cohorts studying
      acute HCV infection (InC(3) study). Individuals with persistent HCV and
      detectable HCV RNA during early chronic infection (one year [+/-4 months]
      postinfection) were included. Distribution of HCV RNA levels during early chronic
      infection was compared by selected host and virological factors. A total of 308
      individuals were included. Median HCV RNA levels were significantly higher among
      males (vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with
      HIV co-infection (vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic
      regression, male sex (vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01,
      3.69), interferon lambda 4 (IFNL4) rs12979860 CC genotype (vs TT/CT; AOR: 2.48;
      95%CI: 1.42, 4.35), HIV co-infection (vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93)
      and HCV genotype G2 (vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently
      associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In
      conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex,
      HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in
      early chronic infection. These factors exert their role as early as one year
      following infection.

PMID- 25580525
TI  - Essential competencies in nursing education for prevention and care related to
      unintended pregnancy.
AB  - OBJECTIVES: To identify the essential competencies for prevention and care
      related to unintended pregnancy to develop program outcomes for nursing
      curricula. DESIGN: Modified Delphi study. SETTING: National. PARTICIPANTS: Eighty
      five nurse experts, including academic faculty and advanced practice nurses
      providing sexual and reproductive health care in primary or specialty care
      settings. METHODS: Expert panelists completed a three-round Delphi study using an
      electronic survey. RESULTS: Eighty-five panelists completed the first round
      survey, and 72 panelists completed all three rounds. Twenty-seven items achieved
      consensus of at least 75% of the experts by the third round to comprise the
      educational competencies. CONCLUSION: Through an iterative process, experts in
      prevention and care related to unintended pregnancy reached consensus on 27 core
      educational competencies for nursing education. The competencies provide a
      framework for curricular development in an important area of nursing education.

PMID- 25580526
TI  - eta6-Cycloparaphenylene transition metal complexes: synthesis, structure,
      photophysical properties, and application to the selective monofunctionalization
      of cycloparaphenylenes.
AB  - The synthesis, structure, photophysical properties, and reactivity of
      cycloparaphenylenes (CPPs) coordinated to group 6 transition metal fragments are
      described. The eta(6)-coordination of [9]CPP or [12]CPP with M(CO)6 (M = Cr, Mo,
      W) afforded the corresponding [n]CPP-M(CO)3 complexes (n = 9, 12; M = Cr, Mo, W).
      In the (1)H NMR spectra of these complexes, characteristic upfield-shifted
      singlet signals corresponding to the four hydrogen atoms attached to the
      coordinated C6H4 ring of the CPPs were observed at 5.4-5.9 ppm. The complex
      [9]CPP-Cr(CO)3 could be successfully isolated in spite of its instability. X-ray
      crystallographic analysis and computational studies of [9]CPP-Cr(CO)3 revealed
      that chromium-CPP coordination occurs at the convex surface of [9]CPP both in the
      solid state and in solution. TD-DFT calculations suggested that the emerging high
      wavenumber absorption peak upon coordination of [9]CPP to Cr(CO)3 should be
      assigned to a weak HOMO-LUMO transition. Moreover, by using the complex [9]CPP
      Cr(CO)3, a rapid and highly monoselective CPP functionalization has been
      achieved. The established one-pot method, consisting of complexation,
      deprotonation, nucleophilic substitution, and decomplexation steps, yielded silyl
      , boryl-, and methoxycarbonyl-substituted CPPs in up to 93% yield relative to
      reacted starting material. 

PMID- 25580527
TI  - Mechanisms of ATM Activation.
AB  - The ataxia-telangiectasia mutated (ATM) protein kinase is a master regulator of
      the DNA damage response, and it coordinates checkpoint activation, DNA repair,
      and metabolic changes in eukaryotic cells in response to DNA double-strand breaks
      and oxidative stress. Loss of ATM activity in humans results in the pleiotropic
      neurodegeneration disorder ataxia-telangiectasia. ATM exists in an inactive state
      in resting cells but can be activated by the Mre11-Rad50-Nbs1 (MRN) complex and
      other factors at sites of DNA breaks. In addition, oxidation of ATM activates the
      kinase independently of the MRN complex. This review discusses these mechanisms
      of activation, as well as the posttranslational modifications that affect this
      process and the cellular factors that affect the efficiency and specificity of
      ATM activation and substrate phosphorylation. I highlight functional similarities
      between the activation mechanisms of ATM, phosphatidylinositol 3-kinases (PI3Ks),
      and the other PI3K-like kinases, as well as recent structural insights into their
      regulation. 

PMID- 25580528
TI  - Form follows function: the importance of endoplasmic reticulum shape.
AB  - The endoplasmic reticulum (ER) has a remarkably complex structure, composed of a
      single bilayer that forms the nuclear envelope, along with a network of sheets
      and dynamic tubules. Our understanding of the biological significance of the
      complex architecture of the ER has improved dramatically in the last few years.
      The identification of proteins and forces required for maintaining ER shape, as
      well as more advanced imaging techniques, has allowed the relationship between ER
      shape and function to come into focus. These studies have also revealed
      unexpected new functions of the ER and novel ER domains regulating alterations in
      ER dynamics. The importance of ER structure has become evident as recent research
      has identified diseases linked to mutations in ER-shaping proteins. In this
      review, we discuss what is known about the maintenance of ER architecture, the
      relationship between ER structure and function, and diseases associated with
      defects in ER structure. 

PMID- 25580530
TI  - Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials.
AB  - Most randomized trials in critical care report no mortality benefit; this may
      reflect competing pathogenic mechanisms, patient heterogeneity, or true
      ineffectiveness of interventions. We hypothesize that in acute respiratory
      distress syndrome (ARDS), randomizing only those patients who show a favorable
      physiological response to an intervention would help ensure that only those
      likely to benefit would be entered into the study. If true, this would decrease
      study "noise" and reduce required sample size, thereby increasing the chances of
      finding true-positive outcomes. It would also lessen the chances of exposing
      patients to treatments that are unlikely to help or that could cause harm. We
      present a reanalysis of randomized clinical trials of positive end-expiratory
      pressure in ARDS that support this hypothesis. 

PMID- 25580531
TI  - Angiotensin II can directly induce mitochondrial dysfunction, decrease oxidative
      fibre number and induce atrophy in mouse hindlimb skeletal muscle.
AB  - NEW FINDINGS: What is the central question of this study? Does angiotensin II
      directly induce skeletal muscle abnormalities? What is the main finding and its
      importance? Angiotensin II induces skeletal muscle abnormalities and reduced
      exercise capacity. Mitochondrial dysfunction and a decreased number of oxidative
      fibres are manifest early, while muscle atrophy is seen later. Thus, angiotensin
      II may play an important role in the skeletal muscle abnormalities observed in a
      wide variety of diseases. Skeletal muscle abnormalities, such as mitochondrial
      dysfunction, a decreased percentage of oxidative fibres and atrophy, are the main
      cause of reduced exercise capacity observed in ageing and various diseases,
      including heart failure. The renin-angiotensin system, particularly angiotensin
      II (Ang II), is activated in the skeletal muscle in these conditions. Here, we
      examined whether Ang II could directly induce these skeletal muscle abnormalities
      and investigated their time course. Angiotensin II (1000 ng kg(-1)  min(-1) ) or
      vehicle was administered to male C57BL/6J mice (10-12 weeks of age) via
      subcutaneously implanted osmotic minipumps for 1 or 4 weeks. Angiotensin II
      significantly decreased body and hindlimb skeletal muscle weights compared with
      vehicle at 4 weeks. In parallel, muscle cross-sectional area was also decreased
      in the skeletal muscle at 4 weeks. Muscle RING finger-1 and atrogin-1 were
      significantly increased in the skeletal muscle from mice treated with Ang II. In
      addition, cleaved caspase-3 and terminal deoxynucleotidyl trasferase-mediated
      dUTP nick-positive nuclei were significantly increased in mice treated with Ang
      II at 1 and 4 weeks, respectively. Mitochondrial oxidative enzymes, such as
      citrate synthase, complex I and complex III activities were significantly
      decreased in the skeletal muscle from mice treated Ang II at 1 and 4 weeks.
      NAD(P)H oxidase-derived superoxide production was increased. NADH staining
      revealed that type I fibres were decreased and type IIb fibres increased in mice
      treated with Ang II at 1 week. The work and running distance evaluated by a
      treadmill test were significantly decreased in mice treated with Ang II at 4
      weeks. Thus, Ang II could directly induce the abnormalities in skeletal muscle
      function and structure.

PMID- 25580529
TI  - DNA triplet repeat expansion and mismatch repair.
AB  - DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic
      stability through rectification of DNA replication errors and attenuation of
      chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair
      has been implicated as a cause of triplet repeat expansions that cause
      neurological diseases such as Huntington disease and myotonic dystrophy. This
      mutagenic process requires the mismatch recognition factor MutSbeta and the
      MutLalpha (and/or possibly MutLgamma) endonuclease, and is thought to be
      triggered by the transient formation of unusual DNA structures within the
      expanded triplet repeat element. This review summarizes the current knowledge of
      DNA mismatch repair involvement in triplet repeat expansion, which encompasses in
      vitro biochemical findings, cellular studies, and various in vivo transgenic
      animal model experiments. We present current mechanistic hypotheses regarding
      mismatch repair protein function in mediating triplet repeat expansions and
      discuss potential therapeutic approaches targeting the mismatch repair pathway. 

PMID- 25580532
TI  - Profiling of ubiquitination pathway genes in peripheral cells from patients with
      frontotemporal dementia due to C9ORF72 and GRN mutations.
AB  - We analysed the expression levels of 84 key genes involved in the regulated
      degradation of cellular protein by the ubiquitin-proteasome system in peripheral
      cells from patients with frontotemporal dementia (FTD) due to C9ORF72 and GRN
      mutations, as compared with sporadic FTD and age-matched controls. A
      SABiosciences PCR array was used to investigate the transcription profile in a
      discovery population consisting of six patients each in C9ORF72, GRN, sporadic
      FTD and age-matched control groups. A generalized down-regulation of gene
      expression compared with controls was observed in C9ORF72 expansion carriers and
      sporadic FTD patients. In particular, in both groups, four genes, UBE2I, UBE2Q1,
      UBE2E1 and UBE2N, were down-regulated at a statistically significant (p < 0.05)
      level. All of them encode for members of the E2 ubiquitin-conjugating enzyme
      family. In GRN mutation carriers, no statistically significant deregulation of
      ubiquitination pathway genes was observed, except for the UBE2Z gene, which
      displays E2 ubiquitin conjugating enzyme activity, and was found to be
      statistically significant up-regulated (p = 0.006). These preliminary results
      suggest that the proteasomal degradation pathway plays a role in the pathogenesis
      of FTD associated with TDP-43 pathology, although different proteins are altered
      in carriers of GRN mutations as compared with carriers of the C9ORF72 expansion. 

PMID- 25580533
TI  - Long non-coding RNAs in cancer and development: where do we go from here?
AB  - Recent genome-wide expression profiling studies have uncovered a huge amount of
      novel, long non-protein-coding RNA transcripts (lncRNA). In general, these
      transcripts possess a low, but tissue-specific expression, and their nucleotide
      sequences are often poorly conserved. However, several studies showed that
      lncRNAs can have important roles for normal tissue development and regulate
      cellular pluripotency as well as differentiation. Moreover, lncRNAs are
      implicated in the control of multiple molecular pathways leading to gene
      expression changes and thus, ultimately modulate cell proliferation, migration
      and apoptosis. Consequently, deregulation of lncRNA expression contributes to
      carcinogenesis and is associated with human diseases, e.g., neurodegenerative
      disorders like Alzheimer's Disease. Here, we will focus on some major challenges
      of lncRNA research, especially loss-of-function studies. We will delineate
      strategies for lncRNA gene targeting in vivo, and we will briefly discuss
      important consideration and pitfalls when investigating lncRNA functions in
      knockout animal models. Finally, we will highlight future opportunities for
      lncRNAs research by applying the concept of cross-species comparison, which might
      contribute to novel disease biomarker discovery and might identify lncRNAs as
      potential therapeutic targets. 

PMID- 25580534
TI  - Structure and function of SET and MYND domain-containing proteins.
AB  - SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid
      Nervy-DEAF1) domain-containing proteins (SMYD) have been found to methylate a
      variety of histone and non-histone targets which contribute to their various
      roles in cell regulation including chromatin remodeling, transcription, signal
      transduction, and cell cycle control. During early development, SMYD proteins are
      believed to act as an epigenetic regulator for myogenesis and cardiomyocyte
      differentiation as they are abundantly expressed in cardiac and skeletal muscle.
      SMYD proteins are also of therapeutic interest due to the growing list of
      carcinomas and cardiovascular diseases linked to SMYD overexpression or
      dysfunction making them a putative target for drug intervention. This review will
      examine the biological relevance and gather all of the current structural data of
      SMYD proteins. 

PMID- 25580535
TI  - HCN channels--modulators of cardiac and neuronal excitability.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a
      family of cation channels activated by hyperpolarized membrane potentials and
      stimulated by intracellular cyclic nucleotides. The four members of this family,
      HCN1-4, show distinct biophysical properties which are most evident in the
      kinetics of activation and deactivation, the sensitivity towards cyclic
      nucleotides and the modulation by tyrosine phosphorylation. The four isoforms are
      differentially expressed in various excitable tissues. This review will mainly
      focus on recent insights into the functional role of the channels apart from
      their classic role as pacemakers. The importance of HCN channels in the cardiac
      ventricle and ventricular hypertrophy will be discussed. In addition, their
      functional significance in the peripheral nervous system and nociception will be
      examined. The data, which are mainly derived from studies using transgenic mice,
      suggest that HCN channels contribute significantly to cellular excitability in
      these tissues. Remarkably, the impact of the channels is clearly more pronounced
      in pathophysiological states including ventricular hypertrophy as well as neural
      inflammation and neuropathy suggesting that HCN channels may constitute promising
      drug targets in the treatment of these conditions. This perspective as well as
      the current therapeutic use of HCN blockers will also be addressed. 

PMID- 25580536
TI  - MicroRNA expression profiling of lactating mammary gland in divergent phenotype
      swine breeds.
AB  - MicroRNA (miRNA) plays a key role in development and specific biological
      processes, such as cell proliferation, differentiation, and apoptosis. Extensive
      studies of mammary miRNAs have been performed in different species and tissues.
      However, little is known about porcine mammary gland miRNAs. In this study, we
      report the identification and characterization of miRNAs in the lactating mammary
      gland in two distinct pig breeds, Jinhua and Yorkshire. Many miRNAs were detected
      as significantly differentially expressed between the two libraries. Among the
      differentially expressed miRNAs, many are known to be related to mammary gland
      development and lactation by interacting with putative target genes in previous
      studies. These findings suggest that miRNA expression patterns may contribute
      significantly to target mRNA regulation and influence mammary gland development
      and peak lactation performance. The data we obtained provide useful information
      about the roles of miRNAs in the biological processes of lactation and the
      mechanisms of target gene expression and regulation. 

PMID- 25580538
TI  - Correction: Kang, K.A.; et al., Myricetin Protects Cells against Oxidative Stress
      Induced Apoptosis via Regulation of PI3K/Akt and MAPK Signaling Pathways. Int. J.
      Mol. Sci. 2010, 11, 4348-4360.
AB  - The authors want to change Figure 1 of the paper published in IJMS [1]. In Figure
      1, 5-position of OH was at 6-position. Therefore, Figure 1 is revised as follows.
      The authors would like to apologize for any inconvenience caused to the readers
      by this change.[...]. 

PMID- 25580537
TI  - Prediction of mature microRNA and piwi-interacting RNA without a genome reference
      or precursors.
AB  - The discovery of novel microRNA (miRNA) and piwi-interacting RNA (piRNA) is an
      important task for the understanding of many biological processes. Most of the
      available miRNA and piRNA identification methods are dependent on the
      availability of the organism's genome sequence and the quality of its annotation.
      Therefore, an efficient prediction method based solely on the short RNA reads and
      requiring no genomic information is highly desirable. In this study, we propose
      an approach that relies primarily on the nucleotide composition of the read and
      does not require reference genomes of related species for prediction. Using an
      empirical Bayesian kernel method and the error correcting output codes framework,
      compact models suitable for large-scale analyses are built on databases of known
      mature miRNAs and piRNAs. We found that the usage of an L1-based Gaussian kernel
      can double the true positive rate compared to the standard L2-based Gaussian
      kernel. Our approach can increase the true positive rate by at most 60% compared
      to the existing piRNA predictor based on the analysis of a hold-out test set.
      Using experimental data, we also show that our approach can detect about an order
      of magnitude or more known miRNAs than the mature miRNA predictor, miRPlex. 

PMID- 25580539
TI  - Do island plant populations really have lower genetic variation than mainland
      populations? Effects of selection and distribution range on genetic diversity
      estimates.
AB  - Ecological and evolutionary studies largely assume that island populations
      display low levels of neutral genetic variation. However, this notion has only
      been formally tested in a few cases involving plant taxa, and the confounding
      effect of selection on genetic diversity (GD) estimates based on putatively
      neutral markers has typically been overlooked. Here, we generated nuclear
      microsatellite and plastid DNA sequence data in Periploca laevigata, a plant
      taxon with an island-mainland distribution area, to (i) investigate whether
      selection affects GD estimates of populations across contrasting habitats; and
      (ii) test the long-standing idea that island populations have lower GD than their
      mainland counterparts. Plastid data showed that colonization of the Canary
      Islands promoted strong lineage divergence within P. laevigata, which was
      accompanied by selective sweeps at several nuclear microsatellite loci. Inclusion
      of loci affected by strong divergent selection produced a significant downward
      bias in the GD estimates of the mainland lineage, but such underestimates were
      substantial (>14%) only when more than one loci under selection were included in
      the computations. When loci affected by selection were removed, we did not find
      evidence that insular Periploca populations have less GD than their mainland
      counterparts. The analysis of data obtained from a comprehensive literature
      survey reinforced this result, as overall comparisons of GD estimates between
      island and mainland populations were not significant across plant taxa (N = 66),
      with the only exception of island endemics with narrow distributions. This study
      suggests that identification and removal of markers potentially affected by
      selection should be routinely implemented in estimates of GD, particularly if
      different lineages are compared. Furthermore, it provides compelling evidence
      that the expectation of low GD cannot be generalized to island plant populations.

PMID- 25580540
TI  - Experimental and DFT studies on the aggregation behavior of imidazolium-based
      surface-active ionic liquids with aromatic counterions in aqueous solution.
AB  - Two imidazolium-based surface-active ionic liquids with aromatic counterions,
      namely, 1-dodecyl-3-methylimidazolium salicylate (C12mimSal) and 1-dodecyl-3
      methylimidazolium 3-hydroxy-2-naphthoate (C12mimHNC), were synthesized, and their
      aggregate behavior in aqueous solutions was systematically explored. Surface
      tension and conductivity measurements indicate that both C12mimSal and C12mimHNC
      show superior surface activity compared to the common imidazolium-based SAIL with
      the same hydrocarbon chain length, 1-dodecyl-3-methylimidazolium bromide
      (C12mimBr). This result demonstrates that the incorporation of aromatic
      counterions favors the formation of micelles. C12mimHNC displays a higher surface
      activity than C12mimSal, resulting from the different hydrophobicities of the
      counterions. In comparison with C12mimBr, C12mimSal not only can form hexagonal
      liquid-crystalline phase (H1) in aqueous solution, but also exhibits a broad
      region of cubic liquid-crystalline phase (V2) at higher concentration. As for the
      C12mimHNC/H2O system, a lamellar liquid-crystalline (L(alpha)) phase was
      observed. These lyotropic liquid crystals (LLCs) were characterized by polarized
      optical microscopy (POM) and small-angle X-ray scattering (SAXS). Structural
      parameters calculated from SAXS patterns suggest that a higher concentration of
      the SAIL leads to a denser arrangement whereas a higher temperature results in
      the opposite effect. The rheological results manifest that the formed H1 phase in
      the C12mimSal/H2O system exhibits an impressive viscoelastic behavior, indicated
      by a modulus (G' and G") that is 1 order of magnitude higher than that of
      C12mimBr. Density functional theory (DFT) calculations reveal that C12mimSal has
      a more negative interaction energy with a water molecule and the Sal(-)
      counterion presents a stronger electronegativity than the HNC(-) counterion. The
      specific phase behavior of the C12mimSal/H2O and C12mimHNC/H2O systems can be
      attributed to the strong synergic interaction between the imidazolium cation and
      the aromatic counterion, including electrostatic attraction, hydrophobic
      interaction, and especially pi-pi interaction.

PMID- 25580541
TI  - Risk factors for pre- and post-engraftment bloodstream infections after
      allogeneic hematopoietic stem cell transplantation.
AB  - BACKGROUND: Bloodstream infections (BSI) are frequently observed after allogeneic
      hematopoietic stem cell transplant (HSCT), and could cause morbidity and
      mortality. METHODS: We retrospectively evaluated the incidence, characteristics
      of, and risk factors for BSI at both pre- and post-engraftment in 209 adult HSCT
      patients at our institute between June 2006 and December 2013. The median age at
      transplantation was 45 years (range, 15-65). A total of 122 patients received
      bone marrow, 68 received peripheral blood stem cells, and 19 received umbilical
      cord blood. RESULTS: The cumulative incidences of pre- and post-engraftment BSI
      were 38.9% and 17.2%, respectively. Nine patients had both pre- and post
      engraftment BSI. In the pre- and post-engraftment periods, respectively, 67.4%
      and 84.1% of isolates were gram-positive bacteria (GPB), 28.3% and 11.4% were
      gram-negative bacteria (GNB), and 4.3% and 4.5% were fungi. Coagulase-negative
      staphylococci were the most commonly isolated GPB, while Stenotrophomonas
      maltophilia and Pseudomonas aeruginosa were the most commonly isolated GNB. Pre
      engraftment BSI was associated with an increased risk of death. Overall survival
      at day 180 for patients with or without pre-engraftment BSI was 70.0% and 82.7%,
      respectively (P = 0.02). CONCLUSIONS: Risk factors for BSI in the pre-engraftment
      period were the interval between diagnosis and transplantation (261 days or
      more), engraftment failure, and high-risk disease status at HSCT in a
      multivariate analysis. No significant risk factor for BSI in the post-engraftment
      period was identified by a univariate analysis. These findings may be useful for
      deciding upon empiric antibacterial treatment for HSCT recipients.

PMID- 25580542
TI  - Successful detection of pathogenic Shiga-toxin-producing Escherichia coli in
      shellfish, environmental waters and sediment using the ISO/TS-13136 method.
AB  - The presence of highly pathogenic Shiga-toxin-producing Escherichia coli (STEC)
      in shellfish, upstream waters and sediment from coastal shellfish sites was
      evaluated using the ISO/TS-13136 method. Shellfish (oysters, mussels and
      cockles), water and sediment samples were collected monthly over a period of 1
      year. The method used real-time PCR detection of stx1, stx2 and eae genes and
      genetic markers corresponding to the five major serogroups (O157, O26, O103, O111
      and O145) on enrichment broths and the identification of STEC when these genes
      and markers were detected. stx genes were detected in the broth of 33% of
      shellfish batches (n = 126), 91% of water samples (n = 117) and 28% of sediment
      (n = 39). One stx1(+), eae(+) O26:H11 strain was isolated from a shellfish batch,
      and O26:H11, O145:H28 and O103:H2 strains without the stx gene (n = 9) were
      isolated from shellfish and waters. In conclusion, this study shows the
      suitability of the ISO/TS-13136 method to assess the presence of highly
      pathogenic E. coli strains in shellfish farming areas. It also highlights a low
      prevalence of STEC and consequently suggests a reduced corresponding human health
      risk. SIGNIFICANCE AND IMPACT OF THE STUDY: (STEC) infections have been reported
      following ingestion of contaminated food or water or after bathing in
      contaminated waters. However, to date, few studies concerning their detection in
      coastal environment and shellfish have been reported. The aim of this work was to
      assess the presence of STEC in three shellfish-harvesting areas by the ISO/TS
      13136 method, which has recently been used for STEC detection in food.

PMID- 25580554
TI  - The effectiveness of screening with interferon-gamma release assays in a
      university health care setting with a diverse global population.
AB  - OBJECTIVE: This analysis examined the effectiveness of utilizing interferon-gamma
      release assay (IGRA) technology in a TB (TB) screening program at a university.
      PARTICIPANTS: Participants were 2299 students at a Montana university who had
      presented to the university health center for TB screening during 2012 and 2013.
      METHODS: A retrospective study was conducted utilizing data from student health
      center medical records. Time and financial expenditures were determined, and the
      cost of the present screening process and 2 alternative scenarios was calculated.
      RESULTS: The current process is the most costly and time-consuming scenario for
      TB testing. Testing exclusively with IGRAs is the least labor-intensive for staff
      and creates revenue, whereas a dual method, utilizing IGRAs for high-risk
      students and skin tests for others, provides a solution that better responds to
      the demographic of the population. CONCLUSIONS: This assessment shows that IGRAs
      are a cost-effective tool for screening a global student population.

PMID- 25580543
TI  - Introduction of chemically labile substructures into Arabidopsis lignin through
      the use of LigD, the Calpha-dehydrogenase from Sphingobium sp. strain SYK-6.
AB  - Bacteria-derived enzymes that can modify specific lignin substructures are
      potential targets to engineer plants for better biomass processability. The Gram
      negative bacterium Sphingobium sp. SYK-6 possesses a Calpha-dehydrogenase (LigD)
      enzyme that has been shown to oxidize the alpha-hydroxy functionalities in beta-O
      4-linked dimers into alpha-keto analogues that are more chemically labile. Here,
      we show that recombinant LigD can oxidize an even wider range of beta-O-4-linked
      dimers and oligomers, including the genuine dilignols, guaiacylglycerol-beta
      coniferyl alcohol ether and syringylglycerol-beta-sinapyl alcohol ether. We
      explored the possibility of using LigD for biosynthetically engineering lignin by
      expressing the codon-optimized ligD gene in Arabidopsis thaliana. The ligD cDNA,
      with or without a signal peptide for apoplast targeting, has been successfully
      expressed, and LigD activity could be detected in the extracts of the transgenic
      plants. UPLC-MS/MS-based metabolite profiling indicated that levels of oxidized
      guaiacyl (G) beta-O-4-coupled dilignols and analogues were significantly elevated
      in the LigD transgenic plants regardless of the signal peptide attachment to
      LigD. In parallel, 2D NMR analysis revealed a 2.1- to 2.8-fold increased level of
      G-type alpha-keto-beta-O-4 linkages in cellulolytic enzyme lignins isolated from
      the stem cell walls of the LigD transgenic plants, indicating that the
      transformation was capable of altering lignin structure in the desired manner. 

PMID- 25580555
TI  - NiTi based stent for the treatment of acute urinary retention due to benign
      prostatic hyperplasia: a preliminary study on NiTi wires and tubes under pure
      bending.

PMID- 25580558
TI  - Structure and catalytic activities of ferrous centers confined on the interface
      between carbon nanotubes and humic acid.
AB  - Preparation of heterogeneous catalysts with active ferrous centers is of great
      significance for industrial and environmental catalytic processes. Nanostructured
      carbon materials (NCM), which possess free-flowing pi electrons, can coordinate
      with transition metals, provide a confinement environment for catalysis, and act
      as potential supports or ligands to construct analogous complexes. However,
      designing such catalysts using NCM is still seldom studied to date. Herein, we
      synthesized a sandwich structured ternary complex via the coordination of Fe
      loaded humic acid (HA) with C=C bonds in the aromatic rings of carbon nanotubes
      (CNTs), in which the O/N-Fe-C interface configuration provides the confinement
      environment for the ferrous sites. The experimental and theoretical results
      revealed octahedrally/tetrahedrally coordinated geometry at Fe centers, and the
      strong hybridization between CNT C pi* and Fe 3d orbitals induces discretization
      of the atomic charges on aromatic rings of CNTs, which facilitates O2 adsorption
      and electron transfer from carbon to O2, which enhances O2 activation. The O2
      activation by the novel HA/Fe-CNT complex can be applied in the oxidative
      degradation of phenol red (PR) and bisphenol A (BPA) in aqueous media.

PMID- 25580559
TI  - Desmocollin-specific antibodies in a patient with Hailey-Hailey disease.

PMID- 25580560
TI  - A review of current practices to increase Chlamydia screening in the community--a
      consumer-centred social marketing perspective.
AB  - BACKGROUND: Chlamydia trachomatis is one of the most frequently reported sexually
      transmitted infections (STI) in Australia, the UK and Europe. Yet, rates of
      screening for STIs remain low, especially in younger adults. OBJECTIVE: To assess
      effectiveness of Chlamydia screening interventions targeting young adults in
      community-based settings, describe strategies utilized and assess them according
      to social marketing benchmark criteria. SEARCH STRATEGY: A systematic review of
      relevant literature between 2002 and 2012 in Medline, Web of Knowledge, PubMed,
      Scopus and the Cumulative Index to Nursing and Allied Health was undertaken.
      RESULTS: Of 18 interventions identified, quality of evidence was low.
      Proportional screening rates varied, ranging from: 30.9 to 62.5% in educational
      settings (n = 4), 4.8 to 63% in media settings (n = 6) and from 5.7 to 44.5% in
      other settings (n = 7). Assessment against benchmark criteria found that
      interventions incorporating social marketing principles were more likely to
      achieve positive results, yet few did this comprehensively. Most demonstrated
      customer orientation and addressed barriers to presenting to a clinic for
      screening. Only one addressed barriers to presenting for treatment after a
      positive result. Promotional messages typically focused on providing facts and
      accessing a testing kit. Risk assessment tools appeared to promote screening
      among higher risk groups. Few evaluated treatment rates following positive
      results; therefore, impact of screening on treatment rates remains unknown.
      DISCUSSION: Future interventions should consider utilizing a comprehensive social
      marketing approach, using formative research to increase insight and segmentation
      and tailoring of screening interventions. Easy community access to both screening
      and treatment should be prioritized.

PMID- 25580561
TI  - Spatiotemporal and Ecological Patterns of Mycobacterium microti Infection in Wild
      Boar (Sus scrofa).
AB  - Mycobacterium microti has recently been described as the causative agent of
      tuberculosis-like lesions in wild boar (Sus scrofa), a reservoir specie of
      Mycobacterium tuberculosis complex (MTBC) in some European Mediterranean
      ecosystem. Through a five-year survey on tuberculosis in free-living wild boars,
      the epidemiological trend of M. microti infections and the host and population
      risk factors linked with its occurrence were described. Retropharyngeal and
      mandibular lymph nodes of 3041 hunted wild boars from six different districts
      were macroscopically inspected. The sex and age of each animal were registered,
      as well as the animal abundance in each district. Lesions compatible with
      tuberculosis (190) were collected and analysed using a gyrB PCR-RFLP assay. M.
      microti was identified directly in 99 tissue samples (Prev = 3.26%; 95% CI: 2.67
      3.97%), while neither Mycobacterium bovis, nor other members of the MTBC were
      detected. The probability of being M. microti positive showed spatio-temporal
      variability, with 26% of increase of risk of being infected for each year.
      Moreover, a positive effect of wild boar abundance and age on the prevalence was
      detected. The generalized increase in the European wild boar population, coupled
      with its sensitivity to M. microti infection, poses a future concern for the
      identification and management of MTBC members in wild boar. 

PMID- 25580563
TI  - Dopant-controlled morphology evolution of WO3 polyhedra synthesized by RF thermal
      plasma and their sensing properties.
AB  - In this paper, a simple way is developed for the synthesis of Cr-doped WO3
      polyhedra controlled by tailoring intrinsic thermodynamic properties in RF
      thermal plasma. Scanning electron microscopy, transmission electron microscopy, X
      ray diffraction, and X-ray photoelectron spectroscopy are used to characterize
      the detail structures and surface/near-surface chemical compositions of the as
      prepared products. Kinetic factors showed little effects on the equilibrium
      morphology of Cr-doped WO3 polyhedra, while equilibrium morphologies of WO3
      polyhedra can be controlled by the thermodynamic factor (Cr doping). Set crystal
      growth habits of pure WO3 as an initial condition, coeffects of distortions
      introduced by Cr into the WO3 matrix, and a chromate layer on the crystal surface
      could reduce the growth rates along [001], [010], and [100] directions. The
      morphology evolution was turning out as the following order with increasing Cr
      dopants: octahedron-truncated octahedron-cuboid. 2.5 at. % Cr-doped WO3 polyhedra
      exhibit the highest sensing response due to coeffects of exposed crystal facets,
      activation energy, catalytic effects of Cr, and particle size on the surface
      reaction and electron transport units. By simply decorating Au on Cr-doped WO3
      polyhedra, the sensing responses, detection limit, and response-recovery
      properties were significantly improved. 

PMID- 25580562
TI  - beta-Hydroxybutyric acid inhibits growth hormone-releasing hormone synthesis and
      secretion through the GPR109A/extracellular signal-regulated 1/2 signalling
      pathway in the hypothalamus.
AB  - beta-Hydroxybutyric acid (BHBA) has recently been shown to regulate hormone
      synthesis and secretion in the hypothalamus. However, little is known about the
      effects of BHBA-mediated hormone regulation or the detailed mechanisms by which
      BHBA regulates growth hormone-releasing hormone (GHRH) synthesis and secretion.
      In the present study, we examined the expression of the BHBA receptor GPR109A in
      primary hypothalamic cell cultures. We hypothesised that BHBA regulates GHRH via
      GPR109A and its downstream signals. Initial in vivo studies conducted in rats
      demonstrated that GHRH mRNA expression in the hypothalamus was strongly inversely
      correlated with BHBA levels in the cerebrospinal fluid during postnatal
      development (r = -0.89, P < 0.01). Furthermore, i.c.v. administration of BHBA
      acutely decreased GHRH mRNA expression in rats. Further in vitro studies revealed
      a decrease in GHRH synthesis and secretion in primary hypothalamic cells after
      treatment with BHBA; this effect was inhibited when hypothalamic cells were
      pretreated with pertussis toxin (PTX). BHBA had no effect on GHRH synthesis and
      secretion in GT1-7 cells, which do not exhibit cell surface expression of
      GPR109A. Furthermore, BHBA acutely decreased the transcription of the homeobox
      gene for Gsh-1 in the hypothalamus in both in vivo and in vitro, and this effect
      was also inhibited by PTX in vitro. In primary hypothalamic cells, BHBA activated
      the extracellular signal-regulated kinase (ERK)1/2, p38 and c-Jun N-terminal
      kinase mitogen-activated protein kinase (MAPK) kinases, as shown by western blot
      analysis. Moreover, inhibition of ERK1/2 with U0126 attenuated the BHBA-mediated
      reduction in Gsh-1 expression and GHRH synthesis and secretion. These results
      strongly suggest that BHBA directly regulates GHRH synthesis and secretion via
      the GPR109A/ERK1/2 MAPK pathway, and also that Gsh-1 is essential for this
      function.

PMID- 25580564
TI  - Development of a novel quantitative PCR assay as a measurement for the presence
      of geosmin-producing fungi.
AB  - AIMS: To provide an efficient technique for monitoring the off-flavoured fungal
      compound geosmin. METHODS AND RESULTS: Geosmin-associated gpe1 gene of
      Penicillium expansum displayed >=99% similarity to cytochrome P450 gene of
      geosmin-producing P. restrictum, but <=40% similarities to geosmin biosynthesis,
      non-cytochromic gene of Streptomyces avermitilis and cytochrome P450 genes of non
      geosmin-producing Neotyphodium lolii, Phoma betae and P. paxilli. Serial 10-fold
      dilutions of P. expansum's DNA was subjected to a previously reported qPCR assay
      (Atoui et al. 2007), utilizing gpe1 specific primer pair 'SNgpe1F/SNgpe1R'. A
      linear relationship between DNA quantity and Cycle Threshold (Ct ), with strong
      correlative coefficient, was observed. Using the available physico-chemical
      method, geosmin was quantified in 188 grape samples. Penicillium spp's DNA was
      quantified in these samples, utilizing the developed qPCR assay. A strong
      positive correlation (R(2)  = 0.97) between Penicillium's DNA and geosmin
      concentration was observed. Furthermore, <50 ng MUl(-1) Penicillium's DNA
      corresponds to geosmin level below the permitted intensity limit i.e. 4, for
      'Flavour Profile Analysis'. CONCLUSIONS: Penicillium spp., genomic DNA level can
      provide an efficient way to quantify geosmin. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This particular qPCR technique can be utilized in numerous food
      industries, for the timely detection and monitoring of geosmin contamination.

PMID- 25580565
TI  - Rhodium-catalyzed (5+1) annulations between 2-alkenylphenols and allenes: a
      practical entry to 2,2-disubstituted 2H-chromenes.
AB  - Readily available alkenylphenols react with allenes under rhodium catalysis to
      provide valuable 2,2-disubstituted 2H-chromenes. The whole process, which
      involves the cleavage of one C-H bond of the alkenyl moiety and the participation
      of the allene as a one-carbon cycloaddition partner, can be considered a simple,
      versatile, and atom-economical (5+1) heteroannulation. The reaction tolerates a
      broad range of substituents both in the alkenylphenol and in the allene, and most
      probably proceeds through a mechanism involving a rhodium-catalyzed C-C coupling
      followed by two sequential pericyclic processes.

PMID- 25580567
TI  - Structural features of colloidal species in the human fasted upper small
      intestine.
AB  - OBJECTIVES: This paper aims to study the features of colloidal species in the
      lumen of the upper small intestine of two healthy adults at fasted state by means
      of electron microscopy. METHODS: Samples were aspirated from a location near the
      ligament of Treitz 30 min (volunteer no. 1, Aspirate30min sample) and 60 min
      (volunteer no. 2, Aspirate60min sample), after administration of 240 ml of an
      aqueous solution in the fasted state. KEY FINDINGS: In the Aspirate30min sample
      micelles coexist with multi-, oligo- and unilamellar vesicles. Tubular structures
      and long structures were frequently visualised. In the Aspirate60min sample
      micelles, few unilamellar vesicles, long structures and tubular structures were
      the dominating structural features. In both samples, multivesicular structures
      and faceted vesicles (previously visualised at fed state) were absent. Structural
      features of both samples bear similarities with previously studied samples from
      the lower intestine in the fasted state. Micelles and unilamellar vesicles
      observed in both samples closely resemble morphological characteristics of those
      found in fluids simulating the colloidal species in fasted upper intestinal
      environment. CONCLUSIONS: Features of colloidal species in contents of fasted
      small intestine have similarities with fluids simulating the contents in fasted
      upper small intestine and with contents of lower intestine in the fasted state.

PMID- 25580566
TI  - Children with epilepsy and anxiety: Subcortical and cortical differences.
AB  - OBJECTIVE: Using a hypothesis-driven approach, subcortical and cortical regions
      implicated in anxiety disorders in the general population were examined in
      children with recent-onset epilepsy with versus without anxiety compared to
      controls. This study reports frequency of anxiety disorders while examining
      familial, clinical, and demographic variables associated with anxiety in children
      with epilepsy. METHOD: Participants included 88 children with epilepsy aged 8-18
      years: 25 with a current anxiety disorder and 63 children with epilepsy and no
      current anxiety disorder. Forty-nine controls without anxiety disorders were
      included. T1 volumetric magnetic resonance imaging (MRI) scans were collected;
      subcortical volumes and cortical thickness were computed using the FreeSurfer
      image analysis suite. Analyses focused on adjusted measures of subcortical
      volumes and cortical thickness. RESULTS: Relative to controls, larger left
      amygdala volumes were found in the Epilepsy with Anxiety group compared to the
      Epilepsy without Anxiety group (p = 0.027). In the hippocampus, there were no
      significant differences between groups. Examination of cortical thickness
      demonstrated that the Epilepsy with Anxiety group showed thinning in left medial
      orbitofrontal (p = 0.001), right lateral orbitofrontal (p = 0.017), and right
      frontal pole (p = 0.009). There were no differences between groups in age, sex,
      IQ, age of onset, medications, or duration of epilepsy. There were more family
      members with a history of anxiety disorders in the Epilepsy with Anxiety group
      compared to the Epilepsy without Anxiety group (p = 0.005). SIGNIFICANCE: Anxiety
      is a common psychiatric comorbidity in children with recent-onset epilepsy with
      volumetric enlargement of the amygdala and thinner cortex in orbital and other
      regions of prefrontal cortex, suggesting structural abnormalities in brain
      regions that are part of the dysfunctional networks reported in individuals with
      anxiety disorders in the general population. These findings are evident early in
      the course of epilepsy, are not related to chronicity of seizures, and may be
      linked to a family history of anxiety and depressive disorders.

PMID- 25580568
TI  - Anti-HLA antibody testing in hematology patients.
AB  - Anti-human leukocyte antigens (HLA) antibodies can adversely impact the care of
      hematology patients. In particular, HLA antibody testing provides important
      information for optimal stem cell and platelet donor selection in the management
      of stem cell recipients and platelet refractory patients. Current testing methods
      for HLA antibodies are briefly reviewed, with particular emphasis on laboratory
      and clinical issues associated with solid-phase multiplex assays.

PMID- 25580569
TI  - Comparison of genome-wide and gene-specific DNA methylation between ART and
      naturally conceived pregnancies.
AB  - Data linking assisted reproductive technologies (ART) with aberrant DNA
      methylation is limited and inconclusive. In addition, most studies to date have
      analyzed only a small number of CpG sites and focused on methylation changes in
      placentas, while data on cord blood are scarce. Our aim was to compare DNA
      methylation in cord blood samples from ART (N = 10) and control pregnancies (N =
      8) using a genome-wide approach with the Illumina(r) Infinium Human Methylation27
      array, which interrogates 27,578 CpG sites. A total of 733 (2.7%) of the CpG
      sites were significantly differentially methylated between the 2 groups (P <
      0.05), with an overall relative hypomethylation in the ART group (P < 0.001).
      Differences in DNA methylation were more pronounced for CpG sites in certain
      types of genomic locations and were related to baseline methylation levels and
      distance from CpG islands and transcription start sites. ART was associated with
      significantly higher variation in DNA methylation, suggesting that differences in
      DNA methylation between cases and controls may result from stochastic (or random)
      genome-wide changes in DNA methylation in ART pregnancies. We identified 24
      candidate genes with 2 or more CpG sites that were significantly different
      between the IVF and control groups. The current study provides support for the
      hypothesis that ART or associated subfertility may be associated with genome-wide
      changes in DNA methylation, and these changes appear to be, at least in part, due
      to epigenetic instability in ART pregnancies. Further studies are required in
      order to determine the extent to which such ART-related epigenetic instability
      may have phenotypic consequences. 

PMID- 25580570
TI  - Sitagliptin, a dipeptidyl peptidase-4 inhibitor, improves recognition memory,
      oxidative stress and hippocampal neurogenesis and upregulates key genes involved
      in cognitive decline.
AB  - AIM: To examine whether prolonged dipeptidyl peptidase-4 (DPP-4) inhibition can
      reverse learning and memory impairment in high-fat-fed mice. METHODS: High-fat
      fed mice received oral sitagliptin (50 mg/kg body weight) once daily or saline
      vehicle over 21 days. An additional group of mice on standard chow received
      saline vehicle. Energy intake, body weight, glucose and insulin concentrations
      were measured at regular intervals. Glucose tolerance, insulin sensitivity, novel
      object recognition, DPP-4 activity, hormone analysis, hippocampal gene expression
      and histology were performed. RESULTS: Sitagliptin decreased circulating DPP-4
      activity and improved glucose tolerance, glucose-stimulated insulin secretion and
      insulin sensitivity, and reduced plasma triglycerides and cholesterol levels. DPP
      4 inhibition improved recognition memory (1.2-fold increase) without affecting
      hypermoteric activity or anxiety levels. Improvement in memory and learning was
      linked to reduced immunostaining for 8-oxoguanine and increased doublecortin
      staining in the hippocampus, which were indicative of reduced brain oxidative
      stress and increased hippocampal neurogenesis, respectively. These effects were
      associated with significant upregulation of hippocampal gene expression of
      glucagon-like peptide-1 (GLP-1) receptor, glucose-dependent insulinotropic
      polypeptide receptor, synaptophysin, sirtuin 1, glycogen synthase kinase 3beta,
      superdioxide mutase 2, nuclear factor (erythroid-derived 2)-like 2 and vascular
      endothelial growth factor. Total plasma and brain GLP-1 concentrations were
      significantly increased after sitagliptin therapy, whereas DPP-4 activity in
      brain tissue was not altered. CONCLUSION: These studies show that sitagliptin can
      reverse memory impairment in high-fat-fed mice and is also associated with
      improved insulin sensitivity, enhanced hippocampal neurogenesis and reduced
      oxidative stress. DPP-4 inhibitors may therefore exhibit dual benefits by
      improving metabolic control and reducing the decline in cognitive function.

PMID- 25580571
TI  - Infectious Complications of Intrathecal Drug Administration Systems for
      Spasticity and Chronic Pain: 145 Patients From a Tertiary Care Center.
AB  - OBJECTIVES: Studies on the use of intrathecal perfusion devices (IPD) are still
      limited and therefore the aim of this study is to access the infectious
      complications associated to these devices. MATERIALS AND METHODS: A retrospective
      analysis of 145 patients who had an IPD implanted at the Chronic Pain Unit of
      Hospital de Sao Joao over the last 20 years. Mean follow-up time was 7.24 years
      (range: 0.47-17.41 years). Intrathecal antispastic drug perfusion was used in 123
      patients (84.8%) and intrathecal analgesia in 22 patients. RESULTS: A total of 19
      (8.71%) infections involving the IPD were identified of which, 14 (6.4%) were
      surgical site infections (SSIs). Methicillin-sensitive Staphylococcus aureus was
      the most commonly isolated bacteria in this group. Superficial SSIs were treated
      with oral antibiotic treatment or local wound care, while in deep SSI the pump
      was removed. Meningitis was identified in 5 (2.3%) patients and was always
      preceded by deep surgical site infections, some of which were already being
      treated with intravenous antibiotics. Median time to meningitis development was
      2.2 months (IQR 82.58 months), after the introduction of the pump. Pump removal
      with anti-biotherapy were the treatment of choice. One patient died of a septic
      shock with associated meningitis and urinary tract infection. CONCLUSIONS: As
      seen in this study, infectious complications following implantation of IPD are
      not uncommon and include a variety of microorganisms. Antibiotic therapy without
      pump removal may be enough for superficial surgical site infections, but our data
      suggests that pump removal is the treatment of choice for deep infections as the
      infection may proceed to meningitis.

PMID- 25580572
TI  - Regulation and governance of multinational drug trials in stroke: barriers and
      possibilities.
AB  - Over the last 10 years, there has been stagnation in the number of multinational
      drug trials in stroke in Europe. One important cause of this is probably the
      increased burden of laws and regulations that came with the European Union
      Clinical Trials Directive. The main objective of research regulation and
      governance should be to protect research participants, their tissues, and data,
      but the approval systems are complex, regulation is variably interpreted and
      enforced, and the assessment of studies is often not proportionate to the risk of
      the research to participants. Such unnecessary barriers should be reduced by
      simplifying, centralizing, and harmonizing the application process, and by
      applying regulatory and governance requirements in a way that is proportionate to
      the potential harms to the patients. The traditional functions of a regulator (in
      setting, monitoring, and enforcing quality standards) could also be supplemented
      with an aim to actively help researchers achieve these standards, for example, by
      giving advice, and ultimately with an aim to facilitate and promote research, for
      example, by integrating research in everyday clinical practice. Research networks
      offer one way of integrating research and clinical practice across multiple
      centers, and can streamline research delivery by supporting researchers deal
      professionally and efficiently with the regulations and governance requirements. 

PMID- 25580574
TI  - Light treatment improves sleep quality and negative affectiveness in high arctic
      residents during winter.
AB  - The seasonal extremes of photoperiod in the high Arctic place particular strain
      on the human circadian system, which leads to trouble sleeping and increased
      feelings of negative affect in the winter months. To qualify for our study,
      potential participants had to have been at Canadian Forces Station (CFS) Alert
      (82 degrees  30' 00" N) for at least 2 weeks. Subjects filled out questionnaires
      regarding sleep difficulty, psychological well-being and mood and wore Actigraphs
      to obtain objective sleep data. Saliva was collected at regular intervals on two
      occasions, 2 weeks apart, to measure melatonin and assess melatonin onset.
      Individuals with a melatonin rhythm that was in disaccord with their sleep
      schedule were given individualized daily light treatment interventions based on
      their pretreatment salivary melatonin profile. The light treatment prescribed to
      seven of the twelve subjects was effective in improving sleep quality both
      subjectively, based on questionnaire results, and objectively, based on the
      actigraphic data. The treatment also caused a significant reduction in negative
      affect among the participants. Since the treatment is noninvasive and has minimal
      associated side effects, our results support the use of the light visors at CFS
      Alert and other northern outposts during the winter for individuals who are
      experiencing sleep difficulty or low mood.

PMID- 25580573
TI  - A fatty acid-dependent hypothalamic-DVC neurocircuitry that regulates hepatic
      secretion of triglyceride-rich lipoproteins.
AB  - The brain emerges as a regulator of hepatic triglyceride-rich very-low-density
      lipoproteins (VLDL-TG). The neurocircuitry involved as well as the ability of
      fatty acids to trigger a neuronal network to regulate VLDL-TG remain unknown.
      Here we demonstrate that infusion of oleic acid into the mediobasal hypothalamus
      (MBH) activates a MBH PKC-delta->KATP-channel signalling axis to suppress VLDL-TG
      secretion in rats. Both NMDA receptor-mediated transmissions in the dorsal vagal
      complex (DVC) and hepatic innervation are required for lowering VLDL-TG,
      illustrating a MBH-DVC-hepatic vagal neurocircuitry that mediates MBH fatty acid
      sensing. High-fat diet (HFD)-feeding elevates plasma TG and VLDL-TG secretion and
      abolishes MBH oleic acid sensing to lower VLDL-TG. Importantly, HFD-induced
      dysregulation is restored with direct activation of either MBH PKC-delta or KATP
      channels via the hepatic vagus. Thus, targeting a fatty acid sensing-dependent
      hypothalamic-DVC neurocircuitry may have therapeutic potential to lower hepatic
      VLDL-TG and restore lipid homeostasis in obesity and diabetes.

PMID- 25580575
TI  - Squamous cell carcinoma in a chronic myelogenous leukemia patient treated with
      imatinib mesylate.

PMID- 25580576
TI  - Control of repeat-protein curvature by computational protein design.
AB  - Shape complementarity is an important component of molecular recognition, and the
      ability to precisely adjust the shape of a binding scaffold to match a target of
      interest would greatly facilitate the creation of high-affinity protein reagents
      and therapeutics. Here we describe a general approach to control the shape of the
      binding surface on repeat-protein scaffolds and apply it to leucine-rich-repeat
      proteins. First, self-compatible building-block modules are designed that, when
      polymerized, generate surfaces with unique but constant curvatures. Second, a set
      of junction modules that connect the different building blocks are designed.
      Finally, new proteins with custom-designed shapes are generated by appropriately
      combining building-block and junction modules. Crystal structures of the designs
      illustrate the power of the approach in controlling repeat-protein curvature. 

PMID- 25580579
TI  - US Transuranium and Uranium Registries case study on accidental exposure to
      uranium hexafluoride.
AB  - The United States Transuranium and Uranium Registries' (USTUR) whole-body donor
      (Case 1031) was exposed to an acute inhalation of uranium hexafluoride (UF6)
      produced from an explosion at a uranium processing plant 65 years prior to his
      death. The USTUR measurements of tissue samples collected at the autopsy
      indicated long-term retention of inhaled slightly enriched uranium material
      (0.85% (235)U) in the deep lungs and thoracic lymph nodes. In the present study,
      the authors combined the tissue measurement results with historical bioassay
      data, and analysed them with International Commission on Radiological Protection
      (ICRP) respiratory tract models and the ICRP Publication 69 systemic model for
      uranium using maximum likelihood and Bayesian statistical methods. The purpose of
      the analysis was to estimate intakes and model parameter values that best
      describe the data, and evaluate their effect on dose assessment. The maximum
      likelihood analysis, which used the ICRP Publication 66 human respiratory tract
      model, resulted in a point estimate of 79 mg of uranium for the occupational
      intake composed of 86% soluble, type F material and 14% insoluble, type S
      material. For the Bayesian approach, the authors applied the Markov Chain Monte
      Carlo method, but this time used the revised human respiratory tract model, which
      is currently being used by ICRP to calculate new dose coefficients for workers.
      The Bayesian analysis estimated that the mean uranium intake was 160 mg, and
      calculated the case-specific lung dissolution parameters with their associated
      uncertainties. The parameters were consistent with the inhaled uranium material
      being predominantly soluble with a small but significant insoluble component. The
      95% posterior range of the rapid dissolution fraction (the fraction of deposited
      material that is absorbed to blood rapidly) was 0.12 to 0.91 with a median of
      0.37. The remaining fraction was absorbed slowly, with a 95% range of 0.000 22 d(
      1) to 0.000 36 d(-1) and a median of 0.000 31 d(-1). The effective dose per unit
      intake calculated using the dissolution parameters derived from the maximum
      likelihood and the Bayesian analyses was higher than the current ICRP dose
      coefficient for type F uranium by a factor of 2 or 7, respectively; the higher
      value of the latter was due to use of the revised respiratory tract model. The
      dissolution parameter values obtained here may be more appropriate to use for
      radiation protection purposes when individuals are exposed to a UF6 mixture that
      contains an insoluble uranium component.

PMID- 25580580
TI  - Post-operative iatrogenic pneumothorax and associated mortality: lessons learnt.

PMID- 25580577
TI  - Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand
      break repair.
AB  - Ctp1 (also known as CtIP or Sae2) collaborates with Mre11-Rad50-Nbs1 to initiate
      repair of DNA double-strand breaks (DSBs), but its functions remain enigmatic. We
      report that tetrameric Schizosaccharomyces pombe Ctp1 contains multivalent DNA
      binding and DNA-bridging activities. Through structural and biophysical analyses
      of the Ctp1 tetramer, we define the salient features of Ctp1 architecture: an N
      terminal interlocking tetrameric helical dimer-of-dimers (THDD) domain and a
      central intrinsically disordered region (IDR) linked to C-terminal 'RHR' DNA
      interaction motifs. The THDD, IDR and RHR are required for Ctp1 DNA-bridging
      activity in vitro, and both the THDD and RHR are required for efficient DSB
      repair in S. pombe. Our results establish non-nucleolytic roles of Ctp1 in
      binding and coordination of DSB-repair intermediates and suggest that ablation of
      human CtIP DNA binding by truncating mutations underlie the CtIP-linked Seckel
      and Jawad syndromes. 

PMID- 25580581
TI  - Expert panel consensus on assessment checklists for a rheumatology objective
      structured clinical examination.
AB  - OBJECTIVE: While several regional fellowship groups conduct rheumatology
      objective structured clinical examinations (ROSCEs), none have been validated for
      use across programs. We aimed to establish agreement among subspecialty experts
      regarding checklist items for several ROSCE stations. METHODS: We administered a
      1-round survey to assess the importance of 173 assessment checklist items for 11
      possible ROSCE stations. We e-mailed the survey to 127 rheumatology educators
      from across the US. Participants rated each item's importance on a 5-point Likert
      scale (1 = not important to 5 = very important). Consensus for high importance
      was predefined as a lower bound of the 95% confidence interval >=4.0. RESULTS:
      Twenty-five individuals (20%) completed the expert panel survey. A total of 133
      of the 173 items (77%) met statistical cutoff for consensus to retain. Several
      items that had population means of >=4.0 but did not meet the predetermined
      definition for consensus were rejected. The percentage of retained items for
      individual stations ranged from 24% to 100%; all items were retained for core
      elements of patient counseling and radiograph interpretation tasks. Only 24% of
      items were retained for a rehabilitation medicine station and 60% for a
      microscope use/synovial fluid analysis station. CONCLUSION: This single-round
      expert panel survey established consensus on 133 items to assess on 11 proposed
      ROSCE stations. The method used in this study, which can engage a diverse
      geographic representation and employs rigorous statistical methods to establish
      checklist content agreement, can be used in any medical field.

PMID- 25580578
TI  - The energy landscape of adenylate kinase during catalysis.
AB  - Kinases perform phosphoryl-transfer reactions in milliseconds; without enzymes,
      these reactions would take about 8,000 years under physiological conditions.
      Despite extensive studies, a comprehensive understanding of kinase energy
      landscapes, including both chemical and conformational steps, is lacking. Here we
      scrutinize the microscopic steps in the catalytic cycle of adenylate kinase,
      through a combination of NMR measurements during catalysis, pre-steady-state
      kinetics, molecular-dynamics simulations and crystallography of active complexes.
      We find that the Mg(2+) cofactor activates two distinct molecular events:
      phosphoryl transfer (>10(5)-fold) and lid opening (10(3)-fold). In contrast,
      mutation of an essential active site arginine decelerates phosphoryl transfer
      10(3)-fold without substantially affecting lid opening. Our results highlight the
      importance of the entire energy landscape in catalysis and suggest that adenylate
      kinases have evolved to activate key processes simultaneously by precise
      placement of a single, charged and very abundant cofactor in a preorganized
      active site. 

PMID- 25580582
TI  - Leptospira and paramyxovirus infection dynamics in a bat maternity enlightens
      pathogen maintenance in wildlife.
AB  - Bats are reservoirs for several zoonotic pathogens of medical importance;
      however, infection dynamics of pathogens in wild bat populations remain poorly
      understood. Here, we examine the influence of host crowding and population age
      structure on pathogen transmission and diversity in bat populations. Focusing on
      two pathogen taxa of medical importance, Leptospira bacteria and paramyxoviruses,
      we monitored host population and pathogen shedding dynamics within a maternity
      colony of the tropical bat species Mormopterus francoismoutoui, endemic to
      Reunion Island. Our data reveal astonishingly similar infection dynamics for
      Leptospira and paramyxoviruses, with infection peaks during late pregnancy and 2
      months after the initial birth pulse. Furthermore, although co-infection occurs
      frequently during the peaks of transmission, the patterns do not suggest any
      interaction between the two pathogens. Partial sequencing reveals a unique bat
      specific Leptospira strain contrasting with the co-circulation of four separate
      paramyxovirus lineages along the whole breeding period. Patterns of infection
      highlight the importance of host crowding in pathogen transmission and suggest
      that most bats developed immune response and stop excreting pathogens. Our
      results support that bat maternity colonies may represent hot spots of
      transmission for bacterial and viral infectious agents, and highlight how
      seasonality can be an important determinant of host-parasite interactions and
      disease emergence. 

PMID- 25580583
TI  - Anti-obesogenic effects of calcium prevent changes in the GLP-1 profile in adult
      rats primed by early weaning.
AB  - SCOPE: Gut peptides regulate appetite and adipogenesis. Early weaning (EW) leads
      to later development of obesity that can be prevented by calcium supplementation.
      We evaluated gut peptides that may have a role in the establishment of this
      dysfunction. METHODS AND RESULTS: At birth, lactating Wistar rats were separated
      in: EW, lactating rats involved with a bandage interrupting the lactation during
      the last 4 days of standard lactation, and C (control) dams whose pups had free
      access to milk during throughout lactation. At 120 days old, half of EW group
      received calcium supplementation (EWCa); EW and C received standard diet. At 21
      days old, EW presented higher glucagon-like peptide 1 (GLP-1) in plasma and
      glucagon-like peptide 1 receptor (GLP1-R) in adipose tissue and hypothalamus, but
      lower GLP-1 and GLP1-R in the gut. At 180 days old, GLP-1 response to food intake
      was blunted in EW and restored by calcium. GLP-1 in the gut was lower in EW and
      its receptor was lower in adipose tissue, and GLP1-R was higher in the gut of
      calcium EW group. CONCLUSION: Thus, EW had short- and long-term effects upon GLP
      1 profile, which may have contributed to obesity development, hyperphagia, and
      insulin resistance due to its adipogenic and appetite control roles. Calcium
      supplementation was able to prevent most of the changes in GLP-1 caused by EW.

PMID- 25580585
TI  - Diffusion-weighted imaging in assessing pathological response of tumor in breast
      cancer subtype to neoadjuvant chemotherapy.
AB  - PURPOSE: To investigate the efficacy of diffusion-weighted imaging (DWI) for
      reflecting and predicting pathological tumor response in breast cancer subtype to
      neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: The retrospective study
      included 176 patients with breast cancer who underwent magnetic resonance imaging
      (MRI) examinations before and after NAC prior to surgery. The pre- and post-NAC
      apparent diffusion coefficient (ADC) values of tumor were measured respectively
      on DWI. The pathological response was classified into either a complete response
      (pCR) or as a noncomplete response (pNCR) to NAC with the Miller & Payne system.
      The relationship between the ADC value and the pathological response was assessed
      according to intrinsic subtypes (Luminal A, Luminal B, HER2-enriched, and triple
      negative) defined by immunohistochemical features. RESULTS: Multiple comparisons
      respectively showed that pre-NAC and post-NAC ADC were significantly different
      among four subtypes (P < 0.001). After the comparison between two different
      subtypes, the pre-NAC ADC value of the triple-negative and HER2-enriched subtypes
      were significantly higher than Luminal A (P < 0.001 and P < 0.001) and Luminal B
      subtype (P < 0.001 and P = 0.009), and the post-NAC ADC of triple-negative
      subtype was significantly higher than the others (P < 0.001). The pre-NAC ADC of
      pCRs was significantly lower than that of pNCRs only in the triple-negative
      subtype among four subtypes (P < 0.001), and the post-NAC ADC of pCRs was
      significantly higher than that of pNCRs in each subtype (P < 0.001). CONCLUSION:
      DWI appears to be a promising tool to determine the association of pathological
      response to NAC in breast cancer subtypes.

PMID- 25580584
TI  - Cannabinoid receptor 1 promotes hepatocellular carcinoma initiation and
      progression through multiple mechanisms.
AB  - Hepatocellular carcinoma (HCC) has high mortality and no adequate treatment.
      Endocannabinoids interact with hepatic cannabinoid 1 receptors (CB1Rs) to promote
      hepatocyte proliferation in liver regeneration by inducing cell cycle proteins
      involved in mitotic progression, including Forkhead Box M1. Because this protein
      is highly expressed in HCC and contributes to its genesis and progression, we
      analyzed the involvement of the endocannabinoid/CB1R system in murine and human
      HCC. Postnatal diethylnitrosamine treatment induced HCC within 8 months in wild
      type mice but fewer and smaller tumors in CB1R(-/-) mice or in wild-type mice
      treated with the peripheral CB1R antagonist JD5037, as monitored in vivo by
      serial magnetic resonance imaging. Genome-wide transcriptome analysis revealed
      CB1R-dependent, tumor-induced up-regulation of the hepatic expression of CB1R,
      its endogenous ligand anandamide, and a number of tumor-promoting genes,
      including the GRB2 interactome as well as Forkhead Box M1 and its downstream
      target, the tryptophan-catalyzing enzyme indoleamine 2,3-dioxygenase. Increased
      indoleamine 2,3-dioxygenase activity and consequent induction of
      immunosuppressive T-regulatory cells in tumor tissue promote immune tolerance.
      CONCLUSION: The endocannabinoid/CB1R system is up-regulated in chemically induced
      HCC, resulting in the induction of various tumor-promoting genes, including
      indoleamine 2,3-dioxygenase; and attenuation of these changes by blockade or
      genetic ablation of CB1R suppresses the growth of HCC and highlights the
      therapeutic potential of peripheral CB1R blockade.

PMID- 25580586
TI  - Isoliquiritigenin as a cause of DNA damage and inhibitor of ataxia-telangiectasia
      mutated expression leading to G2/M phase arrest and apoptosis in oral squamous
      cell carcinoma.
AB  - BACKGROUND: Isoliquiritigenin (ISL), a natural compound extracted from licorice,
      has chemopreventive and antitumor activities. The purpose of this study was to
      investigate the anticancer effect of ISL on human oral squamous cell carcinoma
      (OSCC). METHODS: The anti-OSCC effects of ISL were evaluated using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, flow cytometry,
      reverse transcription-polymerase chain reaction, Western blotting, promoter
      activity, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay,
      malignant phenotype analysis, microRNA, and xenografting. RESULTS: ISL induced
      OSCC cell cycle G2/M phase arrest, apoptosis, and DNA damage. However, the DNA
      repair-associated ataxia telangiectasia mutated (ATM) and phospho-ATM were
      downregulated, ATM mRNA remained unchanged, and the downstream signals were
      inhibited. ATM recovered when the caspase activity was blocked by Z-DVED-FMK. A
      low dose of ISL inhibited OSCC malignancy in vitro and reduced the tumor size in
      vivo. CONCLUSION: ATM was cleaved by ISL-activated caspase, thus inhibiting DNA
      repair in OSCC cells. Therefore, ISL is a promising chemopreventive agent against
      oral cancer. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E360-E371, 2016.

PMID- 25580587
TI  - My foot? Motor imagery-evoked pain, alternative strategies and implications for
      laterality recognition tasks.

PMID- 25580588
TI  - Chemotherapy does not adversely impact outcome following post-incisional hernia
      repair with biomaterial mesh.
AB  - BACKGROUND: Patients receiving chemotherapy are at increased risk for developing
      recurrent or post-incisional hernias (PIH). Biological materials are an
      alternative to synthetic mesh in contaminated fields. The impact of chemotherapy
      on biomaterial tissue ingrowth and integration has not been well studied.
      METHODS: From 2008 to 2011 patients who underwent PIH repair with biomaterial
      mesh (Biodesign(r)) were selected. Patients were divided into two groups: those
      receiving chemotherapy (CT) and those not receiving chemotherapy (NCT). RESULTS:
      Forty-five patients were identified, 28 (62%) in the NCT group and 17 (38%) in
      the CT group. Median follow up for NCT and CT groups were 27 and 17 months,
      respectively. A total of 9/45 (20%) surgical site infections (SSI) were
      diagnosed, with 6/28 (21%) in the NCT and 3/17 (18%) in the CT group (P = 0.53).
      Seroma formation was seen in 5/28 (18%) of NCT patients and 4/17 (23%) in CT
      group (P = 0.46). Overall hernia recurrence rate was 22%, and the rates of
      recurrence were similar among the CT 3/17 (18%) and NCT 7/28 (25%) groups (P =
      0.42). CONCLUSION: The use of perioperative chemotherapy did not increase the
      rate of wound complications following PIH repair with biologic mesh in this group
      of patients.

PMID- 25580589
TI  - Natural-based nanocomposites for bone tissue engineering and regenerative
      medicine: a review.
AB  - Tissue engineering and regenerative medicine has been providing exciting
      technologies for the development of functional substitutes aimed to repair and
      regenerate damaged tissues and organs. Inspired by the hierarchical nature of
      bone, nanostructured biomaterials are gaining a singular attention for tissue
      engineering, owing their ability to promote cell adhesion and proliferation, and
      hence new bone growth, compared with conventional microsized materials. Of
      particular interest are nanocomposites involving biopolymeric matrices and
      bioactive nanosized fillers. Biodegradability, high mechanical strength, and
      osteointegration and formation of ligamentous tissue are properties required for
      such materials. Biopolymers are advantageous due to their similarities with
      extracellular matrices, specific degradation rates, and good biological
      performance. By its turn, calcium phosphates possess favorable osteoconductivity,
      resorbability, and biocompatibility. Herein, an overview on the available natural
      polymer/calcium phosphate nanocomposite materials, their design, and properties
      is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for
      tissue engineering, and processing methodologies are described. The specific
      biological properties of the nanocomposites, as well as their interaction with
      cells, including the use of bioactive molecules, are highlighted. Nanocomposites
      in vivo studies using animal models are also reviewed and discussed. 

PMID- 25580590
TI  - Determination of triazole pesticide residues in edible oils using air-assisted
      liquid-liquid microextraction followed by gas chromatography with flame
      ionization detection.
AB  - In the present study, a rapid, simple, and highly efficient sample preparation
      method based on air-assisted liquid-liquid microextraction followed by gas
      chromatography with flame ionization detection was developed for the extraction,
      preconcentration, and determination of five triazole pesticides (penconazole,
      hexaconazole, diniconazole, tebuconazole, and triticonazole) in edible oils.
      Initially, the oil samples were diluted with hexane and a few microliter of a
      less soluble organic solvent (extraction solvent) in hexane was added. To form
      fine and dispersed extraction solvent droplets, the mixture of oil sample
      solution and extraction solvent is repeatedly aspirated and dispersed with a
      syringe. Under the optimum extraction conditions, the method showed low limits of
      detection and quantification between 2.2-6.1 and 7.3-20 MUg/L, respectively.
      Enrichment factors and extraction recoveries were in the ranges of 71-96 and 71
      96%, respectively. The relative standard deviations for the extraction of 100 and
      250 MUg/L of each pesticide were less than 5% for intraday (n = 6) and interday
      (n = 3) precisions. Finally edible oil samples were successfully analyzed using
      the proposed method, and hexaconazole was found in grape seed oil. 

PMID- 25580591
TI  - The gold(i)-catalysed protodecarboxylation mechanism.
AB  - A mechanistic study of the gold-catalysed protodecarboxylation is described. Each
      reaction step has been investigated experimentally and computationally. More
      specifically, the activation parameters for the decarboxylation step have been
      determined through kinetic studies. Further experimental studies on the
      hydrolysis of the arylgold intermediate have revealed that the protodeauration
      can become competitive with the decarboxylation process at high conversions. This
      switch in rate-limiting step has been shown to be pKa -dependent. These studies
      have been supported by DFT calculations and permit a better understanding of
      which prevalent features of the reaction mechanism account for the
      decarboxylation process. 

PMID- 25580594
TI  - Sugar-coated: exopolysaccharide producing lactic acid bacteria for food and human
      health applications.
AB  - The human enteric microbiome represents a veritable organ relied upon by the host
      for a range of metabolic and homeostatic functions. Through the production of
      metabolites such as short chain fatty acids (SCFA), folate, vitamins B and K,
      lactic acid, bacteriocins, peroxides and exopolysaccharides, the bacteria of the
      gut microbiome provide nutritional components for colonocytes, liver and muscle
      cells, competitively exclude potential pathogenic organisms and modulate the
      hosts immune system. Due to the extensive variation in structure, size and
      composition, microbial exopolysaccharides represent a useful set of versatile
      natural ingredients for the food industrial sector, both in terms of their
      rheological properties and in many cases, their associated health benefits. The
      exopolysaccharide-producing bacteria that fall within the 35 Lactobacillus and
      five Bifidobacterium species which have achieved qualified presumption of safety
      (QPS) and generally recognised as safe (GRAS) status are of particular interest,
      as their inclusion in food products can avoid considerable scrutiny. In addition,
      additives commonly utilised by the food industry are becoming unattractive to the
      consumer, due to the demand for a more 'natural' and 'clean labelled' diet. In
      situ production of exopolysaccharides by food-grade cultures in many cases
      confers similar rheological and sensory properties in fermented dairy products,
      as traditional additives, such as hydrocolloids, collagen and alginate. This
      review will focus on microbial synthesis of exopolysaccharides, the human health
      benefits of dietary exopolysaccharides and the technofunctional applications of
      exopolysaccharide-synthesising microbes in the food industry. 

PMID- 25580593
TI  - Evaluation of the effect of human immunodeficiency virus-related structural
      interventions: the connect to protect project.
AB  - IMPORTANCE: With the emphasis on structural-level interventions that target
      social determinants of human immunodeficiency virus (HIV) transmission to curb
      the HIV epidemic, there is a need to develop evaluation models that can detect
      changes in individual factors associated with HIV-related structural changes.
      OBJECTIVE: To describe whether structural changes developed and achieved by
      community coalitions are associated with an effect on individual factors
      associated with the risk of contracting HIV. DESIGN, SETTING, AND PARTICIPANTS:
      In this serial cross-sectional survey design, data were collected from 8 cities
      during 4 rounds of annual surveys from March 13, 2007, through July 29, 2010.
      Study recruitment took place at venues where the population of focus was known to
      congregate, such as clubs, bars, community centers, and low-income housing. The
      convenience sample of at-risk youth (persons aged 12-24 years) included 5337
      individuals approached about the survey and 3142 (58.9%) who were screened for
      eligibility. Of the 2607 eligible participants, 2559 (98.2%) ultimately agreed to
      participate. INTERVENTIONS: Achievement of locally identified structural changes
      that targeted public and private entities (eg, federal agencies, homeless
      shelters, and school systems) with the goal of fostering changes in policy and
      practice to ultimately facilitate positive behavioral changes aimed at preventing
      HIV. MAIN OUTCOMES AND MEASURES: Number of sexual partners, partner
      characteristics, condom use, and history of sexually transmitted infections and
      HIV testing. RESULTS: Exposure to structural changes was not statistically
      significantly associated with any of the outcome measures, although some results
      were in the direction of a positive structural change effect (eg, a 10-unit
      increase in a structural change score had an odds ratio of 0.88 [95% CI, 0.76
      1.03; P = .11] for having an older sexual partner and an odds ratio of 0.91 [95%
      CI, 0.60-1.39; P = .39] for using a condom half the time or less with a casual
      partner). CONCLUSIONS AND RELEVANCE: This study evaluated a broad representation
      of at-risk individuals and assessed the effect of numerous structural changes
      related to various HIV risk factors. No structural changes as measured in this
      study were associated with a statistically significant reduction in risk
      behaviors. These null findings underscore the need for a long-term approach in
      evaluating structural interventions and the development of more nuanced methods
      of quantifying and comparing structural-change initiatives and determining the
      appropriate strategies for evaluating effect.

PMID- 25580595
TI  - Y-shaped flow-through anastomosis during a flow-through flap transfer.

PMID- 25580592
TI  - Associations between biomarkers and age in the presenilin 1 E280A autosomal
      dominant Alzheimer disease kindred: a cross-sectional study.
AB  - IMPORTANCE: Age-associated changes in brain imaging and fluid biomarkers are
      characterized and compared in presenilin 1 (PSEN1)E280A mutation carriers and
      noncarriers from the world's largest known autosomal dominant Alzheimer disease
      (AD) kindred. OBJECTIVE: To characterize and compare age-associated changes in
      brain imaging and fluid biomarkers in PSEN1 E280A mutation carriers and
      noncarriers. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional measures of 18F
      florbetapir positron emission tomography, 18F-fludeoxyglucose positron emission
      tomography, structural magnetic resonance imaging, cerebrospinal fluid (CSF), and
      plasma biomarkers of AD were assessed from 54 PSEN1 E280A kindred members (age
      range, 20-59 years). MAIN OUTCOMES AND MEASURES: We used brain mapping algorithms
      to compare regional cerebral metabolic rates for glucose and gray matter volumes
      in cognitively unimpaired mutation carriers and noncarriers. We used regression
      analyses to characterize associations between age and the mean cortical to
      pontine 18F-florbetapir standard uptake value ratios, precuneus cerebral
      metabolic rates for glucose, hippocampal gray matter volume, CSF Abeta1-42, total
      tau and phosphorylated tau181, and plasma Abeta measurements. Age at onset of
      progressive biomarker changes that distinguish carriers from noncarriers was
      estimated using best-fitting regression models. RESULTS: Compared with
      noncarriers, cognitively unimpaired mutation carriers had significantly lower
      precuneus cerebral metabolic rates for glucose, smaller hippocampal volume, lower
      CSF Abeta1-42, higher CSF total tau and phosphorylated tau181, and higher plasma
      Abeta1-42 measurements. Sequential changes in biomarkers were seen at age 20
      years (95% CI, 14-24 years) for CSF Abeta1-42, age 16 years (95% CI, 11-24 years)
      for the mean cortical 18F-florbetapir standard uptake value ratio, age 15 years
      (95% CI, 10-24 years) for precuneus cerebral metabolic rate for glucose, age 15
      years (95% CI, 7-20 years) for CSF total tau, age 13 years (95% CI, 8-19 years)
      for phosphorylated tau181, and age 6 years (95% CI, 1-10 years) for hippocampal
      volume, with cognitive decline up to 6 years before the kindred's estimated
      median age of 44 years (95% CI, 43-45 years) at mild cognitive impairment
      diagnosis. No age-associated findings were seen in plasma Abeta1-42 or Abeta1-40.
      CONCLUSIONS AND RELEVANCE: This cross-sectional study provides additional
      information about the course of different AD biomarkers in the preclinical and
      clinical stages of autosomal dominant AD.

PMID- 25580596
TI  - Increased heat requirement for leaf flushing in temperate woody species over 1980
      2012: effects of chilling, precipitation and insolation.
AB  - Recent studies have revealed large unexplained variation in heat requirement
      based phenology models, resulting in large uncertainty when predicting ecosystem
      carbon and water balance responses to climate variability. Improving our
      understanding of the heat requirement for spring phenology is thus urgently
      needed. In this study, we estimated the species-specific heat requirement for
      leaf flushing of 13 temperate woody species using long-term phenological
      observations from Europe and North America. The species were defined as early and
      late flushing species according to the mean date of leaf flushing across all
      sites. Partial correlation analyses were applied to determine the temporal
      correlations between heat requirement and chilling accumulation, precipitation
      and insolation sum during dormancy. We found that the heat requirement for leaf
      flushing increased by almost 50% over the study period 1980-2012, with an average
      of 30 heat units per decade. This temporal increase in heat requirement was
      observed in all species, but was much larger for late than for early flushing
      species. Consistent with previous studies, we found that the heat requirement
      negatively correlates with chilling accumulation. Interestingly, after removing
      the variation induced by chilling accumulation, a predominantly positive partial
      correlation exists between heat requirement and precipitation sum, and a
      predominantly negative correlation between heat requirement and insolation sum.
      This suggests that besides the well-known effect of chilling, the heat
      requirement for leaf flushing is also influenced by precipitation and insolation
      sum during dormancy. However, we hypothesize that the observed precipitation and
      insolation effects might be artefacts attributable to the inappropriate use of
      air temperature in the heat requirement quantification. Rather than air
      temperature, meristem temperature is probably the prominent driver of the leaf
      flushing process, but these data are not available. Further experimental research
      is thus needed to verify whether insolation and precipitation sums directly
      affect the heat requirement for leaf flushing.

PMID- 25580599
TI  - Synthesis of fluorescent naphthoquinolizines via intramolecular Houben-Hoesch
      reaction.
AB  - The repertoire of synthetic methods leading to aza-analogues of polycyclic
      aromatic heterocycles has been enlarged by the discovery of the rearrangement of
      10-substituted benzo[h]quinolines into compounds bearing an azonia-pyrene moiety.
      Acid-mediated intramolecular cyclization of derivatives bearing -CH2 CN and -CH2
      CO2 Et groups led to compounds bearing a 5-substituted benzo[de]pyrido[3,2,1
      ij]quinolinium core. Advanced photophysical studies including time-correlated
      single photon counting (TCSPC) and transient absorption spectroscopy of 5
      aminobenzo[de]pyrido[3,2,1-ij]quinolin-4-ium salt and 5H-benzo[de]pyrido[3,2,1
      ij]quinolin-5-one showed their promising optical properties such as high
      fluorescence quantum yields (37-59%), which was almost independent of the
      solvent, and high tenability of the absorption band position upon changing the
      solvent. The benzo[de]pyrido[3,2,1-ij]quinolinium salt selectively stains nucleic
      acids (in the nucleus and mitochondria) in eukaryotic cells.

PMID- 25580597
TI  - Genomic discovery of potent chromatin insulators for human gene therapy.
AB  - Insertional mutagenesis and genotoxicity, which usually manifest as hematopoietic
      malignancy, represent major barriers to realizing the promise of gene therapy.
      Although insulator sequences that block transcriptional enhancers could mitigate
      or eliminate these risks, so far no human insulators with high functional potency
      have been identified. Here we describe a genomic approach for the identification
      of compact sequence elements that function as insulators. These elements are
      highly occupied by the insulator protein CTCF, are DNase I hypersensitive and
      represent only a small minority of the CTCF recognition sequences in the human
      genome. We show that the elements identified acted as potent enhancer blockers
      and substantially decreased the risk of tumor formation in a cancer-prone animal
      model. The elements are small, can be efficiently accommodated by viral vectors
      and have no detrimental effects on viral titers. The insulators we describe here
      are expected to increase the safety of gene therapy for genetic diseases. 

PMID- 25580598
TI  - Optogenetics enables functional analysis of human embryonic stem cell-derived
      grafts in a Parkinson's disease model.
AB  - Recent studies have shown evidence of behavioral recovery after transplantation
      of human pluripotent stem cell (PSC)-derived neural cells in animal models of
      neurological disease. However, little is known about the mechanisms underlying
      graft function. Here we use optogenetics to modulate in real time
      electrophysiological and neurochemical properties of mesencephalic dopaminergic
      (mesDA) neurons derived from human embryonic stem cells (hESCs). In mice that had
      recovered from lesion-induced Parkinsonian motor deficits, light-induced
      selective silencing of graft activity rapidly and reversibly re-introduced the
      motor deficits. The re-introduction of motor deficits was prevented by the
      dopamine agonist apomorphine. These results suggest that functionality depends on
      graft neuronal activity and dopamine release. Combining optogenetics, slice
      electrophysiology and pharmacological approaches, we further show that mesDA-rich
      grafts modulate host glutamatergic synaptic transmission onto striatal medium
      spiny neurons in a manner reminiscent of endogenous mesDA neurons. Thus,
      application of optogenetics in cell therapy can link transplantation, animal
      behavior and postmortem analysis to enable the identification of mechanisms that
      drive recovery. 

PMID- 25580600
TI  - Positional therapy is worth a try in patients with mild obstructive sleep apnea.
      Point-counterpoint: is avoidance of supine sleep an adequate treatment for OSA?

PMID- 25580601
TI  - Positional therapy: an easy suggestion, but often not the right answer. Point
      counterpoint: is avoidance of supine sleep an adequate treatment for OSA?

PMID- 25580604
TI  - Management of obstructive sleep apnea in a developmentally delayed pediatric
      patient with aggressive behavior and Pierre Robin sequence.
AB  - REPORT OF CASE: This is a case of a 15-year-old nonverbal, developmentally
      delayed boy with history of Fragile X syndrome (FXS), autistic spectrum disorder,
      Pierre Robin sequence (PRS), subglottic stenosis, and ongoing obstructive sleep
      apnea (OSA), who required aggressive surgical intervention. OSA related symptoms
      included loud snoring, apneas, awakenings with gasping breaths, enuresis, and
      daytime sleepiness. The patient also had a history of behavioral problems
      including aggressive behavior, which led to his family and his health care
      providers experiencing challenges caring for him. For example, the patient's
      behavior made examining him very difficult and prevented ENT exam. Likewise, OSA
      was difficult to manage due to the patient's inability to cooperate with
      treatment. The OSA treatment course for this patient is briefly described below.

PMID- 25580602
TI  - Common sleep disorders increase risk of motor vehicle crashes and adverse health
      outcomes in firefighters.
AB  - STUDY OBJECTIVES: Heart attacks and motor vehicle crashes are the leading causes
      of death in US firefighters. Given that sleep disorders are an independent risk
      factor for both of these, we examined the prevalence of common sleep disorders in
      a national sample of firefighters and their association with adverse health and
      safety outcomes. METHODS: Firefighters (n = 6,933) from 66 US fire departments
      were assessed for common sleep disorders using validated screening tools, as
      available. Firefighters were also surveyed about health and safety, and
      documentation was collected for reported motor vehicle crashes. RESULTS: A total
      of 37.2% of firefighters screened positive for any sleep disorder including
      obstructive sleep apnea (OSA), 28.4%; insomnia, 6.0%; shift work disorder, 9.1%;
      and restless legs syndrome, 3.4%. Compared with those who did not screen
      positive, firefighters who screened positive for a sleep disorder were more
      likely to report a motor vehicle crash (adjusted odds ratio 2.00, 95% CI 1.29
      3.12, p = 0.0021) and were more likely to self-report falling asleep while
      driving (2.41, 2.06-2.82, p < 0.0001). Firefighters who screened positive for a
      sleep disorder were more likely to report having cardiovascular disease (2.37,
      1.54-3.66, p < 0.0001), diabetes (1.91, 1.31-2.81, p = 0.0009), depression (3.10,
      2.49-3.85, p < 0.0001), and anxiety (3.81, 2.87-5.05, p < 0.0001), and to report
      poorer health status (p < 0.0001) than those who did not screen positive. Adverse
      health and safety associations persisted when OSA and non-OSA sleep disorders
      were examined separately. CONCLUSIONS: Sleep disorders are prevalent in
      firefighters and are associated with increased risk of adverse health and safety
      outcomes. Future research is needed to assess the efficacy of occupational sleep
      disorders prevention, screening, and treatment programs in fire departments to
      reduce these safety and health risks.

PMID- 25580603
TI  - The Zurich 3-step concept for the management of behavioral sleep disorders in
      children: a before-and-after study.
AB  - OBJECTIVES: Several strategies have been found to be effective for the treatment
      of childhood behavioral sleep disorders. One which has yet to be evaluated is the
      Zurich 3-step concept, which combines basic notions of the two-process model of
      sleep regulation (introducing a regular rhythm and adjusting bedtime to sleep
      need) with behavioral strategies. This uncontrolled before-and-after study
      describes our concept and its step-wise approach, assesses changes in sleep-wake
      variables and behavior problems, and also examines associations between changes
      in sleep-wake variables and behavior problems. METHODS: A total of 79 children
      with sleep problems (age range 6-47 months, 42% females) were included. Sleep
      problems were assessed by the Infant Sleep Questionnaire, sleep-wake variables by
      diary and actigraphy, and behavior problems of children >= 18 months by the Child
      Behavior Checklist. RESULTS: A significant decrease in nocturnal wake duration
      (Cohen's d = -0.34) and a significant increase in the duration of the longest
      continuous nocturnal sleep period (Cohen's d = 0.19) were found from before to
      after intervention (on average 2.7 months, SD 1.5). The variability for sleep
      onset and end time decreased, and actigraphically measured circadian rest
      activity cycle measures improved. Parent-reported internalizing and total
      behavior problems also decreased (Cohen's d = 0.66). CONCLUSIONS: The findings of
      both objective and subjective assessment techniques suggest that the Zurich 3
      step concept is effective. Thus, the intervention concept may be useful in
      clinical practice with sleep-disordered children.

PMID- 25580605
TI  - Time to response with sodium oxybate for the treatment of excessive daytime
      sleepiness and cataplexy in patients with narcolepsy.
AB  - STUDY OBJECTIVES: This post hoc analysis evaluated the time to response that can
      be expected with sodium oxybate (SXB) for treatment of excessive daytime
      sleepiness (EDS) and cataplexy in patients with narcolepsy. METHODS: Data were
      from a 4-week, double-blind, randomized, placebo-controlled trial (GHB-2; N =
      136) of oral SXB 3 g, 6 g, and 9 g nightly, and its 12-month open-label extension
      (GHB-3). Two response definitions were utilized: >= 20% improvement in Epworth
      Sleepiness Scale (ESS) score (EDS responders), and >= 50% reduction in weekly
      cataplexy attacks (cataplexy responders). These thresholds were previously
      determined to be clinically relevant based on analysis of the relationship of
      Clinical Global Impression of Change with ESS and number of cataplexy attacks.
      Kaplan-Meier curves and median times to first response, based on above criteria,
      and to maximum response were estimated. RESULTS: Among 86 patients randomized to
      SXB in GHB-2 and continued into GHB-3, 77.6% and 90.7% were EDS and cataplexy
      responders, respectively. The median (95% CI) times to first response were 37 (31
      50) days for EDS and 25 (17-29) days for cataplexy, and median times to maximum
      response were 106 (85-164) days for EDS and 213 (94-279) days for cataplexy. GHB
      3 results among 31 patients initially randomized to placebo were consistent with
      those treated with SXB throughout, but with longer times to maximum response.
      CONCLUSIONS: Response onset, assessed as clinically meaningful improvements in
      EDS and cataplexy, was observed in most patients within 2 months; a longer period
      is needed to achieve maximum response. Clinicians should recognize that time to
      initial and maximum response may take weeks to months.

PMID- 25580606
TI  - A Comprehensive Evaluation of a Two-Channel Portable Monitor to "Rule in"
      Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVES: We hypothesized that a dual-channel portable monitor (PM)
      device could accurately identify patients who have a high pretest probability of
      obstructive sleep apnea (OSA), and we evaluated factors that may contribute to
      variability between PM and polysomnography (PSG) results. METHODS: Consecutive
      clinic patients (N = 104) with possible OSA completed a home PM study, a PM study
      simultaneous with laboratory PSG, and a second home PM study. Uniform data
      analysis methods were applied to both PM and PSG data. Primary outcomes of
      interest were the positive likelihood ratio (LR+) and sensitivity of the PM
      device to "rule-in" OSA, defined as an apnea-hypopnea index (AHI) >= 5 events/h
      on PSG. Effects of different test environment and study nights, and order of
      study and analysis methods (manual compared to automated) on PM diagnostic
      accuracy were assessed. RESULTS: The PM has adequate LR+ (4.8), sensitivity
      (80%), and specificity (83%) for detecting OSA in the unattended home setting
      when benchmarked against laboratory PSG, with better LR+ (> 5) and specificity
      (100%) and unchanged sensitivity (80%) in the simultaneous laboratory comparison.
      There were no significant night-night (all p > 0.10) or study order effects (home
      or laboratory first, p = 0.08) on AHI measures. Manual PM data review improved
      case finding accuracy, although this was not statistically significant (all p >
      0.07). Misclassification was more frequent where OSA was mild. CONCLUSIONS:
      Overall performance of the PM device is consistent with current recommended
      criteria for an "acceptable" device to confidently "rule-in" OSA (AHI >= 5
      events/h) in a high pretest probability clinic population. Our data support the
      utility of simple two-channel diagnostic devices to confirm the diagnosis of OSA
      in the home environment. COMMENTARY: A commentary on this article appears in this
      issue on page 411.

PMID- 25580607
TI  - Bone loss in obesity and obstructive sleep apnea: a review of literature.
AB  - INTRODUCTION: Obstructive sleep apnea (OSA) is a common sleep-related respiratory
      disorder. It is associated with many endocrinopathies including hypogonadotropic
      hypogonadism, hypercortisolism, and glucose intolerance that may lead to bone
      loss with secondary osteoporosis. METHODS: We report the case of a 41-year-old
      man who presented with bilateral 9th rib fractures and was found to have
      obstructive sleep apnea and osteoporosis. We also present a literature review on
      this topic. RESULTS: OSA can lead to bone loss through various mechanisms. Some
      are shared with obesity, including hypogonadism, altered adrenergic tone,
      inflammation, oxidative stress, vitamin D deficiency and diabetes mellitus;
      others are specific to OSA, such as hypoxia and altered glucocorticoids
      regulation. CONCLUSION: There are no guidelines on screening for osteoporosis in
      OSA. Further research is needed to assess the incidence of bone loss and
      fractures in OSA.

PMID- 25580609
TI  - Evidence that home apnea testing does not follow AASM practice guidelines--or
      Bayes' theorem.

PMID- 25580608
TI  - Obstructive sleep apnea, health-related factors, and long distance heavy vehicle
      crashes in Western Australia: a case control study.
AB  - STUDY OBJECTIVES: To determine the association between obstructive sleep apnea
      (OSA), health-related factors and the likelihood of heavy vehicle crashes in
      Western Australia (WA). METHODS: This case-control study included 100 long-haul
      heavy vehicle drivers who were involved in a police-reported crash in WA during
      the study period (cases) and 100 long-haul heavy vehicle drivers recruited from
      WA truck stops, who were not involved in a crash during the past year (controls).
      Driver demographics, health, and fatigue-related characteristics were obtained
      using an interviewer administered questionnaire. Drivers were tested for OSA
      using a diagnostic Flow Wizard. Logistic regression was used to determine health
      related factors associated with crash involvement among long distance heavy
      vehicle drivers. RESULTS: Heavy vehicle drivers diagnosed with OSA through the
      use of the FlowWizard were over three times more likely to be involved in a crash
      than drivers without OSA (adjusted OR: 3.42, 95% CI: 1.34-8.72). The risk of
      crash was significantly increased if heavy vehicle drivers reported a diagnosis
      of depression (adjusted OR: 6.59, 95% CI: 1.30-33.24) or had not completed
      fatigue management training (adjusted OR: 6.05, 95% CI: 1.80-20.24). Crash risk
      was 74% lower among older drivers (> 35 years) than younger drivers (adjusted OR:
      0.25, 95% CI: 0.08-0.82). CONCLUSION: The results suggest that more rigorous
      screening and subsequent treatment of OSA and depression by clinicians as well as
      compulsory fatigue management training may reduce crashes among heavy vehicle
      drivers. COMMENTARY: A commentary on this article appears in this issue on page
      409.

PMID- 25580610
TI  - Psychometric properties and adaptation of the ASRS in a Spanish sample of
      patients with substance use disorders: Application of two IRT Rasch models.
AB  - The Adult ADHD Self-Report Scale (ASRS; Kessler et al., 2005) is one of the most
      extensively used scales to detect attention-deficit hyperactivity disorder (ADHD)
      in adults. The aim of this work is to analyze the psychometric properties of the
      18 ASRS items in people with substance use disorders (SUDs). Furthermore, we
      aimed to (a) confirm or, if necessary, modify the dichotomization criteria of the
      items proposed by the authors, and (b) identify the most informative items for a
      screening version or, when applicable, confirm the use of the 6 items that
      comprise the initially proposed short version. The ASRS was completed for 170
      patients with SUD at the Provincial Unit for Drug Dependence of Huelva, Spain,
      aged 16 to 78 years. Two Rasch models-the dichotomous Rasch model and the Rating
      Scale Model (RSM) for polytomous items-were used in the psychometric analysis.
      The ASRS items fitted the RSM adequately, but the locations of the items along
      the underlying construct led us to propose new criteria of dichotomization. After
      analyzing the information function of dichotomized items, we identified 6 items
      that should integrate a new screening scale. Our dichotomization proposal is
      different from the original one and takes into account the different weights of
      the items. The selected screening version showed better metric properties than
      the other analyzed versions. Future research should test our proposal by using
      external criteria and to obtain evidences for other populations, cultures, or
      patient profiles.

PMID- 25580611
TI  - The assessment of risky decision making: a factor analysis of performance on the
      Iowa Gambling Task, Balloon Analogue Risk Task, and Columbia Card Task.
AB  - Researchers and clinicians frequently use behavioral measures to assess decision
      making. The most common task that is marketed to clinicians is the Iowa Gambling
      Task (IGT), thought to assess risky decision making. How does performance on the
      IGT relate to performance on other common measures of decision making? The
      present study sought to examine relationships between the IGT, the Balloon
      Analogue Risk Task (BART), and the Columbia Card Task (CCT). Participants were
      390 undergraduate students who completed the IGT, BART, and either the "hot" or
      "cold" CCT. Principal components factor analysis on the IGT, BART, and CCT-cold
      (n = 112) indicated that the IGT measures a different component of decision
      making than the BART, and the CCT-cold weakly correlated with early IGT trials.
      Results of the exploratory factor analysis on the IGT, BART, and CCT-hot (n =
      108) revealed a similar picture: the IGT and BART assessed different types of
      decision making, and the BART and CCT-hot were weakly correlated. A confirmatory
      factor analysis (n = 170) indicated that a 3-factor model without the CCT-cold
      (Factor 1: later IGT trials; Factor 2: BART; and Factor 3: early IGT trials) was
      a better fitting model than one that included the CCT-cold and early IGT trials
      on the same factor. Collectively, the present results suggest that the IGT, BART,
      and CCT all measure unique, nonoverlapping decision making processes. Further
      research is needed to more fully understand the neuropsychological construct of
      decision making.

PMID- 25580613
TI  - Distinguishing between demoralization and specific personality traits in clinical
      assessment with the NEO-PI-R.
AB  - Demoralization, a nonspecific unpleasant state that is common in clinical
      practice, has been identified as a potential source of nonspecificity in the
      assessment of personality and psychopathology. The aim of this research was to
      distinguish between Demoralization and specific personality traits in a widely
      used measure of personality: the Neuroticism-Extraversion-Openness Personality
      Inventory-Revised (NEO-PI-R). NEO-PI-R and Minnesota Multiphasic Personality
      Inventory-2 questionnaires were completed by 278 patients of a specialized clinic
      for personality disorders in The Netherlands. Furthermore, a replication sample
      was used consisting of 405 patients from the same institution who completed NEO
      PI-R questionnaires, as well. A measure of Demoralization was derived (NEOdem, a
      NEO-PI-R-based Demoralization scale) using factor analytic techniques. Results
      indicated that the Demoralization Scale scores were reliable and showed expected
      patterns of convergence and divergence with conceptually relevant Minnesota
      Multiphasic Personality Inventory-2-RF scales. When items contributing to
      Demoralization-related variance were removed from the NEO-PI-R scales, increased
      specificity was notable with regard to external correlates. These results provide
      supportive evidence for the validity and heuristic potential of distinguishing
      between Demoralization and specific personality traits within the NEO-PI-R.

PMID- 25580612
TI  - Psychopathy factor interactions and co-occurring psychopathology: Does
      measurement approach matter?
AB  - The 2 dimensions of psychopathy as operationalized by various measurement tools
      show differential associations with psychopathology; however, evidence suggests
      that the statistical interaction of Factor 1 (F1) and Factor 2 (F2) may be
      important in understanding associations with psychopathology. Findings regarding
      the interactive effects of F1 and F2 are mixed, as both potentiating and
      protective effects have emerged. Moreover, approaches to measuring F1 (e.g.,
      clinical interview vs. self-report) are based on different conceptualizations of
      F1, which may influence the interactive effects. The current study aims to (a)
      elucidate the influence of F1 and F2 on psychopathology by using both variable
      centered and person-centered approaches and (b) determine whether the measurement
      of F1 influences the interactive effects of F1 and F2 by comparing the strength
      of interactive effects across F1 measures in a sample of over 1,500 offenders.
      Across analytic methods, there were very few cases in which F1 statistically
      influenced the association between F2 and psychopathology, such that F1 failed to
      evidence either potentiating or protective effects on F2. Furthermore, the
      conceptualization of F1 across psychopathy measures did not impact the
      interactive effects of F1 and F2. These findings suggest that F2 is probably
      driving the relations between psychopathy and other forms of psychopathology and
      that F1 may play less of a role in interacting with F2 than previously believed.

PMID- 25580614
TI  - On the factor structure of the Rosenberg (1965) General Self-Esteem Scale.
AB  - Since its introduction, the Rosenberg General Self-Esteem Scale (RGSE, Rosenberg,
      1965) has been 1 of the most widely used measures of global self-esteem. We
      conducted 4 studies to investigate (a) the goodness-of-fit of a bifactor model
      positing a general self-esteem (GSE) factor and 2 specific factors grouping
      positive (MFP) and negative items (MFN) and (b) different kinds of validity of
      the GSE, MFN, and MFP factors of the RSGE. In the first study (n = 11,028), the
      fit of the bifactor model was compared with those of 9 alternative models
      proposed in literature for the RGSE. In Study 2 (n = 357), the external
      validities of GSE, MFP, and MFN were evaluated using objective grade point
      average data and multimethod measures of prosociality, aggression, and
      depression. In Study 3 (n = 565), the across-rater robustness of the bifactor
      model was evaluated. In Study 4, measurement invariance of the RGSE was further
      supported across samples in 3 European countries, Serbia (n = 1,010), Poland (n =
      699), and Italy (n = 707), and in the United States (n = 1,192). All in all,
      psychometric findings corroborate the value and the robustness of the bifactor
      structure and its substantive interpretation.

PMID- 25580615
TI  - Development of elastin-like recombinamer films with antimicrobial activity.
AB  - In the present work we explored the ABP-CM4 peptide properties from Bombyx mori
      for the creation of biopolymers with broad antimicrobial activity. An
      antimicrobial recombinant protein-based polymer (rPBP) was designed by cloning
      the DNA sequence coding for ABP-CM4 in frame with the N-terminus of the elastin
      like recombinamer consisting of 200 repetitions of the pentamer VPAVG, here named
      A200. The new rPBP, named CM4-A200, was purified via a simplified
      nonchromatographic method, making use of the thermoresponsive behavior of the
      A200 polymer. ABP-CM4 peptide was also purified through the incorporation of a
      formic acid cleavage site between the peptide and the A200 sequence. In soluble
      state the antimicrobial activity of both CM4-A200 polymer and ABP-CM4 peptide was
      poorly effective. However, when the CM4-A200 polymer was processed into free
      standing films high antimicrobial activity against Gram-positive and Gram
      negative bacteria, yeasts and filamentous fungi was observed. The antimicrobial
      activity of CM4-A200 was dependent on the physical contact of cells with the film
      surface. Furthermore, CM4-A200 films did not reveal a cytotoxic effect against
      both normal human skin fibroblasts and human keratinocytes. Finally, we have
      developed an optimized ex vivo assay with pig skin demonstrating the
      antimicrobial properties of the CM4-A200 cast films for skin applications. 

PMID- 25580616
TI  - Mode specificity in the HCl + OH -> Cl + H2O reaction: Polanyi's rules vs sudden
      vector projection model.
AB  - The dynamics and mode specificity of the HCl + OH -> Cl + H2O reaction are
      investigated using a full-dimensional quantum dynamics method on an accurate
      global potential energy surface. It is shown that the vibrational excitation of
      the HCl reactant greatly enhances the reactivity while the OH vibrational
      excitation has little effect. The surprising HCl vibrational enhancement of this
      early barrier reaction contradicts a naive extension of Polanyi's rules, but can
      be explained by the sudden vector projection model, which attributes the
      promotional effect of the HCl vibration to its strong coupling with the reaction
      coordinate at the transition state. In addition, it is found that the fundamental
      and overtone excitations of the HCl reactant change the reaction mechanism from a
      direct barrier crossing process to a capture-like process. 

PMID- 25580617
TI  - Adding two active silver atoms on Au25 nanoparticle.
AB  - Alloy nanoparticles with atomic monodispersity is of importance for some
      fundamental research (e.g., the investigation of active sites). However, the
      controlled preparation of alloy nanoparticles with atomic monodispersity has long
      been a major challenge. Herein, for the first time a unique method, antigalvanic
      reduction (AGR), is introduced to synthesize atomically monodisperse
      Au25Ag2(SC2H4Ph)18 in high yield (89%) within 2 min. Interestingly, the two
      silver atoms in Au25Ag2(SC2H4Ph)18 do not replace the gold atoms in the precursor
      particle Au25(SC2H4Ph)18 but collocate on Au25, which was supported by
      experimental and calculated results. Also, the two silver atoms are active to
      play roles in stabilizing the alloy nanoparticle, triggering the nanoparticle
      fluorescence and catalyzing the hydrolysis of 1,3-diphenylprop-2-ynyl acetate. 

PMID- 25580618
TI  - Sequence-dependent binding of flavonoids to duplex DNA.
AB  - The whole family of structurally distinct flavonoids has been recognized as a
      valuable source of prospective anticancer agents. There is experimental evidence
      demonstrating that some flavonoids, like flavopiridol (FLP) and quercetin (QUE),
      bind to DNA influencing their key physiological function. FLP is involved in the
      combined mode of interaction (intercalation and minor groove binding), while QUE
      is viewed as a minor groove binder. From a physical standpoint, experimental and
      theoretical studies have not so far provided a sufficiently consistent picture of
      the nature of interaction with DNA. Herein the sequence-dependent binding of FLP
      and of QUE (two representative examples of the structurally different flavonoids)
      with duplex DNA, containing a variety of the sequences of eight nucleotides (I:
      GGGGCCCC, II: GGCCGGCC, III: AAAATTTT, IV: AAGCGCTT, V: GCGCGCGC) in the 5'
      strand, is investigated using a sophisticated molecular dynamics (MD) approach.
      For various parts (helix, backbone, bases) of the DNA structure, the change of
      asymptotic (in terms of an infinite length of MD simulation) configurational
      entropy, being the thermodynamic consequence of DNA flexibility change due to
      ligand binding, is explored. As far as the sequence-dependent extent of DNA
      flexibility change upon QUE (or FLP) binding is concerned, for the entire double
      helix, increased flexibility is observed for I (or I ~ II), while increased
      rigidity is found to be in the order of V > III > II > IV (or III > V > IV) for
      the rest of sequences. For the backbone, increased rigidity in the order of V >
      III > II > IV > I (or III > V > IV > I > II) is generally observed. For the
      nucleobases, increased flexibility is determined for I and II (I > II for both
      ligands), while increased rigidity in the order of V ~ III > IV (or III > V > IV)
      is reported for the other sequences. Of the overall increased rigidity of the DNA
      structure upon ligand binding that is observed for the sequences III, IV, and V,
      about 50-70% comes from the sugar-phosphate backbone. Noteworthy is that the
      increased flexibility of the entire double helix and of the complete system of
      nucleobases upon ligand binding is only established for sequence I. The insights
      are further subtly substantiated by considering the configurational entropy
      contributions at the level of individual nucleobase pairs and of individual
      nucleo-base pair steps and by analyzing the sequence dependent estimates of intra
      base pair entropy and inter-base pair entropy. The GGC triplet, which is part of
      the central tetramer (GGCC) of I, is concluded to be critical for binding of
      flavonoids, while the effect of the presence of ligand to the flexibility of
      nucleobases is localized through the intra-base pair motion of the intercalation
      site and its immediate vicinity. G-rich DNA sequences with consecutive Gs going
      before and/or after the critical GGC code (such as I: GGGGCCCC) are proposed to
      be uniquely specific for flavonoids. The configurational entropy contribution, as
      an upper bound of the true entropy contribution to the free energy in noncovalent
      binding, is demonstrated to influence the fundamental discrimination
      (intercalation vs groove binding) of DNA-flavonoid recognition modes. Some
      interesting implications for the structure-based design of optimal DNA binders
      are discussed. 

PMID- 25580619
TI  - Patterning microparticles on a template of aggregated cationic dye.
AB  - Patternwise aggregation of charged molecules on a surface is potentially a facile
      approach to generate a template on which to pattern oppositely charged
      microparticles. We report on the patterning of silica microparticles by a system
      comprising a photopatternable copolymer and an aggregate forming penta-cationic
      cyanine dye. A thin film of the copolymer, composed of a molar excess of
      styrenesulfonic acid oxime ester to cross-linkable glycidyl methacrylate
      monomomers, was exposed through a mask and neutralized, resulting in a pattern of
      hydrophobic areas, and where exposed, a hydrophilic cross-linked film with sodium
      poly(styrenesulfonate) domains. The occurrence and locus of aggregation of an
      aqueous solution of the dye, applied to the patterned surface was established by
      absorbance and fluorescence spectroscopy and atomic force microscopy. In exposed
      areas, dye is imbibed and aggregation induced in sodium styrenesulfonate domains
      internal to the layer, whereas in the unexposed areas the dye aggregates on the
      hydrophobic surface. Aqueous anionic silica microparticles applied to the dye
      treated patterned surface and then rinsed, are retained in the unexposed areas
      having cationic surface aggregates, but rejected from the exposed areas with
      internal dye aggregates as these areas retain net negative charge. Mask exposure,
      absent dye treatment, did not result in patterning as negatively charged
      microparticles were nowhere retained, and positively charged particles were
      everywhere retained. The extent of surface coverage by the dye in unexposed areas
      was deposition time dependent, and ranged from isolated patches covering about 20
      percent of the polymer surface to a surface saturated layer, with silica particle
      patterning robust over the range of dye surface coverages studied. The force
      requirements to pattern the denser than water silica microparticles are
      identified, and particle and polymer film surface potentials that meet the
      critical repulsion force requirement are mapped using an established sphere-to
      flat surface electric double layer (EDL) model. 

PMID- 25580620
TI  - Pressure-induced conductivity and yellow-to-black piezochromism in a layered Cu
      Cl hybrid perovskite.
AB  - Pressure-induced changes in the electronic structure of two-dimensional Cu-based
      materials have been a subject of intense study. In particular, the possibility of
      suppressing the Jahn-Teller distortion of d(9) Cu centers with applied pressure
      has been debated over a number of decades. We studied the structural and
      electronic changes resulting from the application of pressures up to ca. 60 GPa
      on a two-dimensional copper(II)-chloride perovskite using diamond anvil cells
      (DACs), through a combination of in situ powder X-ray diffraction, electronic
      absorption and vibrational spectroscopy, dc resistivity measurements, and optical
      observations. Our measurements show that compression of this charge-transfer
      insulator initially yields a first-order structural phase transition at ca. 4 GPa
      similar to previous reports on other Cu(II)-Cl perovskites, during which the
      originally translucent yellow solid turns red. Further compression induces a
      previously unreported phase transition at ca. 8 GPa and dramatic piezochromism
      from translucent red-orange to opaque black. Two-probe dc resistivity
      measurements conducted within the DAC show the first instance of appreciable
      conductivity in Cu(II)-Cl perovskites. The conductivity increases by 5 orders of
      magnitude between 7 and 50 GPa, with a maximum measured conductivity of 2.9 * 10(
      4) S.cm(-1) at 51.4 GPa. Electronic absorption spectroscopy and variable
      temperature conductivity measurements indicate that the perovskite behaves as a
      1.0 eV band-gap semiconductor at 39.7 GPa and has an activation energy for
      electronic conduction of 0.232(1) eV at 40.2 GPa. Remarkably, all these changes
      are reversible: the material reverts to a translucent yellow solid upon
      decompression, and ambient pressure powder X-ray diffraction data taken before
      and after compression up to 60 GPa show that the original structure is maintained
      with minimal hysteresis. 

PMID- 25580622
TI  - Comparative study on pyrido[3,4-b]pyrazine-based sensitizers by tuning bulky
      donors for dye-sensitized solar cells.
AB  - Dye-sensitized solar cells (DSSCs) with cobalt electrolytes have gained
      increasing attention. In this Research Article, two new pyrido[3,4-b]pyrazine
      based sensitizers with different cores of bulky donors (indoline for DT-1 and
      triphenylamine for DT-2) were designed and synthesized for a comparative study of
      their photophysical and electrochemical properties and device performance and
      were also analyzed through density functional theory calculations. The results of
      density function theory calculations reveal the limited electronic communication
      between the biphenyl branch at the cis-position of N-phenylindoline and the
      indoline core, which could act as an insulating blocking group and inhibit the
      dye aggregation and charge recombination at the interface of
      TiO2/dye/electrolyte. As expected, DSSCs based on DT-1 with cobalt redox
      electrolyte gained a higher photoelectric conversion efficiency of 8.57% under
      standard AM 1.5 G simulated sunlight, with Jsc = 16.08 mA cm(-2), Voc = 802 mV,
      and FF = 0.66. Both electrochemical impedance spectroscopy (EIS) and intensity
      modulated photovoltage spectroscopy (IMVS) suggest that charge recombination in
      DSSCs based on DT-1 is much less than that in their counterparts of DT-2, owing
      to the bigger donor size and the insulating blocking branch in the donor of DT-1.

PMID- 25580623
TI  - Theoretical description of structural and electronic properties of organic
      photovoltaic materials.
AB  - We review recent progress in the modeling of organic solar cells and photovoltaic
      materials, as well as discuss the underlying theoretical methods with an emphasis
      on dynamical electronic processes occurring in organic semiconductors. The key
      feature of the latter is a strong electron-phonon interaction, making the
      evolution of electronic and structural degrees of freedom inseparable. We discuss
      commonly used approaches for first-principles modeling of this evolution,
      focusing on a multiscale framework based on the Holstein-Peierls Hamiltonian
      solved via polaron transformation. A challenge for both theoretical and
      experimental investigations of organic solar cells is the complex multiscale
      morphology of these devices. Nevertheless, predictive modeling of photovoltaic
      materials and devices is attainable and is rapidly developing, as reviewed here. 

PMID- 25580621
TI  - Araguspongine C induces autophagic death in breast cancer cells through
      suppression of c-Met and HER2 receptor tyrosine kinase signaling.
AB  - Receptor tyrosine kinases are key regulators of cellular growth and
      proliferation. Dysregulations of receptor tyrosine kinases in cancer cells may
      promote tumorigenesis by multiple mechanisms including enhanced cell survival and
      inhibition of cell death. Araguspongines represent a group of macrocyclic
      oxaquinolizidine alkaloids isolated from the marine sponge Xestospongia species.
      This study evaluated the anticancer activity of the known oxaquinolizidine
      alkaloids araguspongines A, C, K and L, and xestospongin B against breast cancer
      cells. Araguspongine C inhibited the proliferation of multiple breast cancer cell
      lines in vitro in a dose-dependent manner. Interestingly, araguspongine C-induced
      autophagic cell death in HER2-overexpressing BT-474 breast cancer cells was
      characterized by vacuole formation and upregulation of autophagy markers
      including LC3A/B, Atg3, Atg7, and Atg16L. Araguspongine C-induced autophagy was
      associated with suppression of c-Met and HER2 receptor tyrosine kinase
      activation. Further in-silico docking studies and cell-free Z-LYTE assays
      indicated the potential of direct interaction between araguspongine C and the
      receptor tyrosine kinases c-Met and HER2 at their kinase domains. Remarkably,
      araguspongine C treatment resulted in the suppression of PI3K/Akt/mTOR signaling
      cascade in breast cancer cells undergoing autophagy. Induction of autophagic
      death in BT-474 cells was also associated with decreased levels of inositol 1,4,5
      trisphosphate receptor upon treatment with effective concentration of
      araguspongine C. In conclusion, results of this study are the first to reveal the
      potential of araguspongine C as an inhibitor to receptor tyrosine kinases
      resulting in the induction of autophagic cell death in breast cancer cells. 

PMID- 25580625
TI  - Advanced physical chemistry of carbon nanotubes.
AB  - The past decade has seen a surge of exciting research and applications of carbon
      nanotubes (CNTs) stimulated by deeper understanding of their fundamental
      properties and increasing production capability. The intrinsic properties of
      various CNTs were found to strongly depend on their internal microstructures.
      This review summarizes the fundamental structure-property relations of seamless
      tube-like single- and multiwalled CNTs and conically stacked carbon nanofibers,
      as well as the organized architectures of these CNTs (including randomly stacked
      thin films, parallel aligned thin films, and vertically aligned arrays). It
      highlights the recent development of CNTs as key components in selected
      applications, including nanoelectronics, filtration membranes, transparent
      conductive electrodes, fuel cells, electrical energy storage devices, and solar
      cells. Particular emphasis is placed on the link between the basic physical
      chemical properties of CNTs and the organized CNT architectures with their
      functions and performance in each application. 

PMID- 25580626
TI  - Biomolecular damage induced by ionizing radiation: the direct and indirect
      effects of low-energy electrons on DNA.
AB  - Many experimental and theoretical advances have recently allowed the study of
      direct and indirect effects of low-energy electrons (LEEs) on DNA damage. In an
      effort to explain how LEEs damage the human genome, researchers have focused
      efforts on LEE interactions with bacterial plasmids, DNA bases, sugar analogs,
      phosphate groups, and longer DNA moieties. Here, we summarize the current
      understanding of the fundamental mechanisms involved in LEE-induced damage of DNA
      and complex biomolecule films. Results obtained by several laboratories on films
      prepared and analyzed by different methods and irradiated with different electron
      beam current densities and fluencies are presented. Despite varied conditions
      (e.g., film thicknesses and morphologies, intrinsic water content, substrate
      interactions, and extrinsic atmospheric compositions), comparisons show a
      striking resemblance in the types of damage produced and their yield functions.
      The potential of controlling this damage using molecular and nanoparticle targets
      with high LEE yields in targeted radiation-based cancer therapies is also
      discussed. 

PMID- 25580627
TI  - The dynamics of molecular interactions and chemical reactions at metal surfaces:
      testing the foundations of theory.
AB  - We review studies of molecular interactions and chemical reactions at metal
      surfaces, emphasizing progress toward a predictive theory of surface chemistry
      and catalysis. For chemistry at metal surfaces, a small number of central
      approximations are typically made: (a) the Born-Oppenheimer approximation of
      electronic adiabaticity, (b) the use of density functional theory at the
      generalized gradient approximation level, (c) the classical approximation for
      nuclear motion, and (d) various reduced-dimensionality approximations. Together,
      these approximations constitute a provisional model for surface chemical
      reactivity. We review work on some carefully studied examples of molecules
      interacting at metal surfaces that probe the validity of various aspects of the
      provisional model. 

PMID- 25580628
TI  - Molecular force spectroscopy on cells.
AB  - Molecular force spectroscopy has become a powerful tool to study how mechanics
      regulates biology, especially the mechanical regulation of molecular interactions
      and its impact on cellular functions. This force-driven methodology has uncovered
      a wealth of new information of the physical chemistry of molecular bonds for
      various biological systems. The new concepts, qualitative and quantitative
      measures describing bond behavior under force, and structural bases underlying
      these phenomena have substantially advanced our fundamental understanding of the
      inner workings of biological systems from the nanoscale (molecule) to the
      microscale (cell), elucidated basic molecular mechanisms of a wide range of
      important biological processes, and provided opportunities for engineering
      applications. Here, we review major force spectroscopic assays, conceptual
      developments of mechanically regulated kinetics of molecular interactions, and
      their biological relevance. We also present current challenges and highlight
      future directions. 

PMID- 25580624
TI  - Site-specific infrared probes of proteins.
AB  - Infrared spectroscopy has played an instrumental role in the study of a wide
      variety of biological questions. However, in many cases, it is impossible or
      difficult to rely on the intrinsic vibrational modes of biological molecules of
      interest, such as proteins, to reveal structural and environmental information in
      a site-specific manner. To overcome this limitation, investigators have dedicated
      many recent efforts to the development and application of various extrinsic
      vibrational probes that can be incorporated into biological molecules and used to
      site-specifically interrogate their structural or environmental properties. In
      this review, we highlight recent advancements in this rapidly growing research
      area. 

PMID- 25580629
TI  - Effect of Polarization on Airway Epithelial Conditioning of Monocyte-Derived
      Dendritic Cells.
AB  - Airway epithelial cells (AECs) form polarized barriers that interact with inhaled
      allergens and are involved in immune homeostasis. We examined how monocyte
      derived dendritic cells (MDDCs) are affected by contact with the airway
      epithelium. In traditional setups, bronchial epithelial cell lines were allowed
      to polarize on filter inserts, and MDDCs were allowed to adhere to the epithelial
      basal side. In an optimized setup, the cell application was reversed, and the
      culture conditions were modified to preserve cellular polarization and integrity.
      These two parameters were crucial for the MDDCs' immunoregulatory properties;
      thus, previous observations obtained using traditional setups should be
      considered with caution. Using the optimized setup, AEC conditioning of MDDCs led
      to increased expression of programmed death 1 ligand 1, immunoglobulin-like
      transcript 3, CD40, CD80, and CD23. This increased expression was accompanied by
      decreased secretion of monocyte chemotactic protein 1 and eotaxin and donor
      variable effects on IL-12 and IL-10 secretion. Conditioning varied between
      maturation states and depended partly on direct contact between AECs and MDDCs.
      The setup allowed MDDCs on the basal side of the epithelium to sample allergens
      administered to the apical side. Allergen uptake depended on polarization and the
      nature of the allergen. AEC conditioning led to decreased birch allergen-specific
      proliferation of autologous T cells and a trend toward decreased secretion of the
      Th2-specific cytokines IL-5 and IL-13. In conclusion, we determined that AEC
      conditioning favoring cellular integrity leads to a tolerogenic MDDC phenotype,
      which is likely to be important in regulating immune responses against commonly
      inhaled allergens. 

PMID- 25580630
TI  - Motivational interviewing intervention with college student tobacco users:
      providers' beliefs and behaviors.
AB  - OBJECTIVE: This study assessed college student health providers' use of
      Motivational Interviewing (MI) with tobacco users, as well as their beliefs about
      the use of brief interventions to help college student tobacco users quit. MI is
      recommended by the United States Public Health Service to increase tobacco users'
      willingness to quit. PARTICIPANTS: Participants included 83 clinicians from
      health clinics at 7 different universities in North Carolina. METHODS: Paper-and
      pencil baseline survey from a cluster randomized trial of college student health
      clinicians. RESULTS: Twenty-two percent of respondents reported always or usually
      using MI during the past month for tobacco-using patients not ready to make a
      quit attempt. Student health providers also reported information with regards to
      their beliefs about tobacco cessation treatment, barriers to intervening with
      patients, and confidence in motivating students to consider quitting.
      CONCLUSIONS: Results highlight the need to encourage clinicians' use of
      motivationally focused interventions with student tobacco users. [Table: see
      text].

PMID- 25580632
TI  - Occupational therapy culture seen through the multifocal lens of fieldwork in
      diverse rural areas.
AB  - BACKGROUND: Existing occupational therapy culture has not yet fully articulated
      diverse worldviews on occupation, health, and well-being and the link between
      them. Taking into consideration the diversity of the global world, incorporating
      different worldviews would be a valuable contribution to expanding the relevance
      of occupational therapy. AIM: The aim of this research was to analyse worldviews
      regarding human occupation and the link between occupation, health, and well
      being among people from rural Honduras, Morocco, Burkina Faso, Tanzania, and
      Ecuador. METHODS: This ethnographic research used three methods, i.e. semi
      structured interviews, participant observations, and in-depth interviews, to
      collect data from 27 participants in five countries. The material was analysed
      using a Grounded Theory approach. RESULTS: One core category, "Occupations are
      social practices", was identified and it included three subcategories:
      "Occupation, health and well-being as a personal and community experience"; "Co
      occupations, collective occupations and collaborative occupations are the most
      important occupations"; and "Occupation, health and well-being mutually influence
      each other". Conclusion and significance. The overall findings showed that taking
      different worldviews into account is needed for developing an occupational
      therapy culture that is useful globally and hosts diverse meanings and occupation
      focused practices.

PMID- 25580631
TI  - Longitudinal assessment of DNA methylation changes during HPVE6E7-induced
      immortalization of primary keratinocytes.
AB  - High-risk human papillomavirus (hrHPV)-induced immortalization and malignant
      transformation are accompanied by DNA methylation of host genes. To determine
      when methylation is established during cell immortalization and whether it is
      hrHPV-type dependent, DNA methylation was studied in a large panel of HPVE6E7
      immortalized keratinocyte cell lines. These cell lines displayed different growth
      behaviors, i.e., continuous growth versus crisis period prior to immortalization,
      reflecting differential immortalization capacities of the 7 HPV-types
      (16/18/31/33/45/66/70) studied. In this study, cells were monitored for
      hypermethylation of 14 host genes (APC, CADM1, CYGB, FAM19A4, hTERT, mir124-1,
      mir124-2, mir124-3, MAL, PHACTR3, PRDM14, RASSF1A, ROBO3, and SFRP2) at 4
      different stages during immortalization. A significant increase in overall
      methylation levels was seen with progression through each stage of
      immortalization. At stage 1 (pre-immortalization), a significant increase in
      methylation of hTERT, mir124-2, and PRDM14 was already apparent, which continued
      over time. Methylation of ROBO3 was significantly increased at stage 2 (early
      immortal), followed by CYGB (stage 3) and FAM19A4, MAL, PHACTR3, and SFRP2 (stage
      4). Methylation patterns were mostly growth behavior independent. Yet, hTERT
      methylation levels were significantly increased in cells that just escaped from
      crisis. Bisulfite sequencing of hTERT confirmed increased methylation in immortal
      cells compared to controls, with the transcription core and known repressor sites
      remaining largely unmethylated. In conclusion, HPV-induced immortalization is
      associated with a sequential and progressive increase in promoter methylation of
      a subset of genes, which is mostly independent of the viral immortalization
      capacity. 

PMID- 25580633
TI  - Depression, self-esteem and sexual function in laryngeal cancer patients.
AB  - OBJECTIVE: The purpose of this study was to assess sexual function, affective
      disorders and self-esteem in patients who were surgically treated for laryngeal
      cancer. DESIGN: Retrospective, blind, cross-sectional study. SETTING: Single
      tertiary cancer centre. PARTICIPANTS: Seventy four patients who were operated on
      Istanbul University Cerrahpasa School of Medicine Otorhinolaryngology Department
      between 2008 and 2012 were classified according to the type of the operation as
      total laryngectomy (Group 1) and partial laryngectomy (Group 2). MAIN OUTCOME
      MEASURES: Sexual dysfunction, depression and self-esteem were evaluated with The
      Arizona Sexual Experiences Scale (ASEX), Beck's Depression Inventory (BDI) and
      Rosenberg Self-Esteem Scale (RSES), respectively. RESULTS: Average ASEX scores of
      the Group 1 were (13.98 +/- 6.32) and Group 2 were (13.08 +/- 4.96) without
      statistically significant difference (P = 0.537). Mean BDI score of Group 1 was
      (13.20 +/- 10.41) higher than Group 2 (7.76 +/- 8.14) and the difference was
      significant statistically (P = 0.026). Mean RSES scores of Group 1 and Group 2
      were 20.68 +/- 5.33 and 19.25 +/- 4.70, respectively, again without significant
      difference (P = 0.262). However, when the average scores of each item of
      Rosenberg Scale were compared, significant difference was found in d4 (2.37 +/-
      0.78; 1.64 +/- 0.99; P = 0.001), d6 (1.22 +/- 1.05; 1.84 +/- 1.14; P = 0.023),
      d10 (2.55 +/- 2.39; 1.28 +/- 1.49; P = 0.018) and d11 (1.35 +/- 0.95; 2.00 +/-
      1.41; P = 0.021). BDI scores were correlated with RSES scores, and ASEX scores
      were correlated with age. CONCLUSION: The patients with total laryngectomy seem
      to have more psychological problems that must be addressed in the postoperative
      period.

PMID- 25580635
TI  - Effect of overweight/obesity on response to periodontal treatment: systematic
      review and a meta-analysis.
AB  - AIM: The objective of this study was to investigate whether the response to
      periodontal treatment differs among obese, overweight or normal-weight patients.
      MATERIALS & METHODS: Both randomized and non-randomized studies were identified
      from searches up to July 2013. Risk of bias was assessed with the Downs-Black
      checklist, the Cochrane tool and the GRADE framework. Quantitative synthesis was
      conducted with random-effects meta-analyses in subgroups for systemically healthy
      and diabetic patients. RESULTS: A total of 15 studies including 867 patients were
      included. No significant difference was found for any clinical periodontal
      parameter between overweight/obese and normal-weight patients. Periodontal
      treatment in systemically healthy overweight/obese patients was associated with
      higher decrease in TNFalpha levels (1 study) and higher decrease in HbA1c levels
      (1 study) compared to systemically healthy normal-weight patients. Contrary to
      diabetic normal-weight patients, periodontal treatment in diabetic
      overweight/obese patients was associated with an increase in adiponectin levels
      (2 studies) and a decrease in leptin levels (2 studies). However, the quality of
      existing evidence is low due to inconsistency, imprecision and lack of studies.
      CONCLUSIONS: Whereas no difference was found in clinical periodontal parameters,
      significant differences in inflammatory or metabolic parameters were found
      between overweight/obese and normal-weight patients, but existing evidence is
      weak.

PMID- 25580636
TI  - Coronary artery bypass graft pseudo-aneurysm following sternal wire removal.

PMID- 25580634
TI  - Immune mechanisms linked to depression via oxidative stress and neuroprogression.
AB  - Emerging evidence suggests the significant role of inflammation and oxidative
      stress as main contributors to the neuroprogression that is observed in major
      depressive disorder (MDD), where patients show increased inflammatory and
      oxidative stress biomarkers. The process of neuroprogression includes stage
      related neurodegeneration, cell death, reduced neurogenesis, reduced neuronal
      plasticity and increased autoimmune responses. Oxidative stress is a consequence
      of the biological imbalance between Reactive Oxygen Species (ROS) and
      antioxidants, leading to the alteration of biomolecules and the loss of control
      of the intracellular redox-related signaling pathways. ROS serve as crucial
      secondary messengers in signal transduction and significantly affect inflammatory
      pathways by activating NF-kappaB and MAPK family stress kinases. When present in
      excess, ROS inflict damage, affecting cellular constituents with the formation of
      pro-inflammatory molecules, such as malondialdehyde, 4-Hydroxynonenal,
      neoepitopes and damage-associated molecular patterns promoting immune response,
      and ultimately leading to cell death. The failure of cells to adapt to the
      changes in redox homeostasis and the subsequent cell death, together with the
      damage caused by inflammatory mediators, have been considered as major causes of
      neuroprogression and hence MDD. Both an activated immune-inflammatory system and
      increased oxidative stress act synergistically, complicating our understanding of
      the pathogenesis of depression. The cascade of antioxidative and inflammatory
      events is orchestrated by several transcription factors, with Nrf2 and NF-kappaB
      having particular relevance to MDD. This review focuses on potential molecular
      mechanisms through which impaired redox homeostasis and neuroinflammation can
      affect the neuronal environment and contribute to depression This article is
      protected by copyright. All rights reserved.

PMID- 25580637
TI  - Geographic range size and extinction risk assessment in nomadic species.
AB  - Geographic range size is often conceptualized as a fixed attribute of a species
      and treated as such for the purposes of quantification of extinction risk;
      species occupying smaller geographic ranges are assumed to have a higher risk of
      extinction, all else being equal. However many species are mobile, and their
      movements range from relatively predictable to-and-fro migrations to complex
      irregular movements shown by nomadic species. These movements can lead to
      substantial temporary expansion and contraction of geographic ranges, potentially
      to levels which may pose an extinction risk. By linking occurrence data with
      environmental conditions at the time of observations of nomadic species, we
      modeled the dynamic distributions of 43 arid-zone nomadic bird species across the
      Australian continent for each month over 11 years and calculated minimum range
      size and extent of fluctuation in geographic range size from these models. There
      was enormous variability in predicted spatial distribution over time; 10 species
      varied in estimated geographic range size by more than an order of magnitude, and
      2 species varied by >2 orders of magnitude. During times of poor environmental
      conditions, several species not currently classified as globally threatened
      contracted their ranges to very small areas, despite their normally large
      geographic range size. This finding raises questions about the adequacy of
      conventional assessments of extinction risk based on static geographic range size
      (e.g., IUCN Red Listing). Climate change is predicted to affect the pattern of
      resource fluctuations across much of the southern hemisphere, where nomadism is
      the dominant form of animal movement, so it is critical we begin to understand
      the consequences of this for accurate threat assessment of nomadic species. Our
      approach provides a tool for discovering spatial dynamics in highly mobile
      species and can be used to unlock valuable information for improved extinction
      risk assessment and conservation planning.

PMID- 25580638
TI  - What do nurse managers say about nurses' sickness absenteeism? A new perspective.
AB  - AIM: To explore nurses' sickness absenteeism from the perspective of nurse
      managers. BACKGROUND: Sickness absenteeism among health-care providers,
      especially nurses, remains a significant problem in an era of challenges to
      provide high quality care with the required skill mix. This in turn compromises
      the quality of care and adds to the costs of an organisation. METHODS: A
      qualitative descriptive design was used. Data were collected from a governmental
      academic hospital in Lebanon. In-depth tape-recorded interviews were conducted
      with a total of 20 nurse managers. Data were analysed through a content analysis
      approach. RESULTS: Data analysis yielded three domains as follows: work-related,
      individual and organisational factors that lead to nurses' sickness absenteeism.
      CONCLUSION: This study conceptualised nurses' absenteeism from the nurse
      managers' perspective, and it revealed absence antecedents that are rarely
      reported elsewhere in the literature. IMPLICATIONS FOR NURSING MANAGEMENT: The
      findings from this study can be utilised to design reform initiatives concerned
      with nurses' absenteeism and to decrease its negative consequences in terms of
      quality and cost.

PMID- 25580639
TI  - Implementation of quality of life monitoring in Dutch routine care of adolescents
      with type 1 diabetes: appreciated but difficult.
AB  - OBJECTIVE: Monitoring quality of life (QoL) improves well-being and care
      satisfaction of adolescents with type 1 diabetes. We set out to evaluate the
      implementation of the program DAWN (Diabetes Attitudes Wishes and Needs) MIND
      Youth (Monitoring Individual Needs in Young People With Diabetes) (DM-Y), in
      which Dutch adolescents' QoL is assessed with the MIND Youth Questionnaire (MY-Q)
      and its outcomes are discussed. Successful implementation of DM-Y warrants close
      study of experienced barriers and facilitators as experienced by diabetes care
      teams as well as adolescents and parents. METHODS: The study was conducted in 11
      self-selected Dutch pediatric diabetes clinics. A mixed methods approach was
      used. Ten diabetes teams (26 members) were interviewed; 36 team members, 29
      adolescents, and 66 parents completed an online survey. RESULTS: Two of 10 teams
      successfully implemented DM-Y. Whereas 92% of teams valued DM-Y as a useful
      addition to routine care, most clinics were not able to continue because of
      logistical problems (lack of time and manpower). Still, all teams had the
      ambition to make DM-Y integral part of routine care in the nearby future. Seventy
      nine percentage of the parents and 41% of the adolescents appreciated the usage
      of MY-Q, same percentage of adolescents neutral. CONCLUSIONS: DM-Y is highly
      appreciated by teams, as well as adolescents and parents, but for most clinics it
      is difficult to implement. More effort should be paid to resolve logistic
      problems in order to facilitate dissemination of DM-Y in care nationwide.

PMID- 25580641
TI  - Prevalence and factors affecting breastfeeding among Aboriginal women in
      Northwestern Ontario.
AB  - OBJECTIVE: To evaluate breastfeeding outcomes among Aboriginal women and to
      determine variables affecting breastfeeding in the early postpartum period.
      DESIGN: Prospective cohort study. SETTING: Two sites in Northwestern Ontario,
      Canada: a tertiary care center and a rural hospital. PARTICIPANTS: One hundred
      thirty breastfeeding Aboriginal women agreed to participate in the study.
      METHODS: All women completed a baseline survey in hospital that included
      questions regarding demographic, prenatal, breastfeeding, obstetric, postpartum,
      and neonatal characteristics. Women were then telephoned at 4 and 8 weeks
      postpartum to complete additional questionnaires regarding infant feeding.
      RESULTS: Low rates of breastfeeding initiation (69%) and exclusive breastfeeding
      were identified at 4 (37.5%) and 8 (35.3%) weeks postpartum. Among those who
      initiated breastfeeding, duration rates at 4 (86%) and 8 weeks (78%) postpartum
      are comparable to other studies. Variables associated with any and exclusive
      breastfeeding at 8 weeks included the following: (a) household income, (b)
      intended breastfeeding duration, (c) plan to exclusively breastfeed, (d)
      perception of meeting their planned duration goal, and (e) higher breastfeeding
      self-efficacy. Partner support was associated with any breastfeeding at 8 weeks
      but not exclusivity. Women who were breastfeeding exclusively in hospital
      (prevalence ratio [PR] = .48, 95% confidence interval [CI] [0.27, 0.86]), did not
      smoke (PR = 2.5, 95% CI [1.4, 4.3]) and/or use substances during pregnancy (PR =
      4.5, 95% CI [1.5, 14]) were more likely to be breastfeeding exclusively at 8
      weeks. CONCLUSION: Many of the variables may be considered modifiable and
      amenable to intervention. Targeted interventions should be directed toward
      improving breastfeeding outcomes among Aboriginal women.

PMID- 25580642
TI  - Limited influence of local and landscape factors on finescale gene flow in two
      pond-breeding amphibians.
AB  - Dispersal and gene flow within animal populations are influenced by the
      composition and configuration of the landscape. In this study, we evaluated
      hypotheses about the impact of natural and anthropogenic factors on genetic
      differentiation in two amphibian species, the spotted salamander (Ambystoma
      maculatum) and the wood frog (Lithobates sylvaticus) in a commercial forest in
      central Maine. We conducted this analysis at two scales: a local level, focused
      on factors measured at each breeding pond, and a landscape level, focused on
      factors measured between ponds. We investigated the effects of a number of
      environmental factors in six categories including Productivity, Physical, Land
      Composition, Land Configuration, Isolation and Location. Embryos were sampled
      from 56 spotted salamander breeding ponds and 39 wood frog breeding ponds. We
      used a hierarchical Bayesian approach in the program GESTE at each breeding pond
      and a random forest algorithm in conjunction with a network analysis between the
      ponds. We found overall high genetic connectivity across distances up to 17 km
      for both species and a limited effect of natural and anthropogenic factors on
      gene flow. We found the null models best explained patterns of genetic
      differentiation at a local level and found several factors at the landscape level
      that weakly influenced gene flow. This research indicates multiscale
      investigations that incorporate local and landscape factors are valuable for
      understanding patterns of gene flow. Our findings suggest that dispersal rates in
      this system are high enough to minimize genetic structuring and that current
      forestry practices do not significantly impede dispersal. 

PMID- 25580640
TI  - Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases
      from colon cancer is correlated to shorter disease-free and overall survival.
AB  - Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4
      signalling pathways in liver metastatic colorectal cancer (CRC) relapse. CXCR2,
      CXCR4, and their chemokine ligands were evaluated in liver metastases of
      colorectal cancer in order to study their correlation with overall and disease
      free survival of patients having received, or not received, a neoadjuvant
      chemotherapy regimen. Quantitative RT-PCR and CXCR2 immunohistochemical staining
      were carried out using CRC liver metastasis samples. Expression levels of CXCR2,
      CXCR4, and their ligands were statistically analyzed according to treatment with
      neoadjuvant chemotherapy and patients' outcome. CXCR2 and CXCL7 overexpression
      are correlated to shorter overall and disease-free survival. By multivariate
      analysis, CXCR2 and CXCL7 expressions are independent factors of overall and
      disease-free survival. Neoadjuvant chemotherapy increases significantly the
      expression of CXCR2: treated group 1.89 (0.02-50.92) vs 0.55 (0.07-3.22), P =
      0.016. CXCL7 was overexpressed close to significance, 0.40 (0.00-7.85) vs 0.15
      (0.01-7.88), P = 0.12. We show the involvement of CXCL7/CXCR2 signalling pathways
      as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based
      chemotherapy regimens increase the expression of these genes in liver metastasis,
      providing one explanation for aggressiveness of relapsed drug-resistant tumors.
      Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential
      therapeutic opportunities.

PMID- 25580643
TI  - Effects of decontamination solutions on the surface of titanium: investigation of
      surface morphology, composition, and roughness.
AB  - AIM: To investigate the impact of treatments used to detoxify dental implants on
      the oxide layer morphology and to infer how changes in morphology created by
      these treatments may impact re-osseointegration of an implant. MATERIALS AND
      METHODS: Pure titanium (cpTi) and the alloy Ti6Al4V were subjected to a series of
      chemical treatments and mechanical abrasion simulating surface decontamination of
      dental implants. The morphology and roughness of the surface layer before and
      after treatment with these solutions were investigated with optical and atomic
      force microscopy (OM, AFM). The solutions employed are typically used for
      detoxification of dental implants. These included citric acid, 15% hydrogen
      peroxide, chlorhexidine gluconate, tetracycline, doxycycline, sodium fluoride,
      peroxyacetic acid, and treatment with carbon dioxide laser. The treatments
      consisted of both immersions of samples in solution and rubbing with cotton swabs
      soaked in solution for 1, 2, and 5 min. Cotton swabs used were analyzed with
      energy dispersive spectroscopy (EDS). RESULTS: The microscopy investigation
      showed that corrosion and pitting of the samples were present in both metal
      grades with immersion and rubbing methods when employing more acidic solutions,
      which had pH <3. Mildly acidic solutions caused surface discoloration when
      coupled with rubbing but did not cause corrosion with immersion. Neutral or basic
      treatments resulted in no signs of corrosion with both methods. EDS results
      revealed the presence of titanium particles on all rubbing samples. CONCLUSION:
      It was demonstrated in this study that acidic environments coupled with rubbing
      are able to introduce noticeable morphological changes and corrosion on the
      surface of both titanium grades.

PMID- 25580645
TI  - Mortality and SUDEP in epilepsy patients treated with vagus nerve stimulation.
AB  - OBJECTIVE: The risk of premature death is increased in patients with intractable
      epilepsy. The effect of vagus nerve stimulation (VNS) on mortality remains
      unclear. In a previous study by Annegers et al., mortality was raised, comparable
      to similar intractable cohorts. Our aim was to calculate standardized mortality
      ratios (SMRs), identify epilepsy-related deaths, and estimate sudden unexpected
      death in epilepsy (SUDEP) rates in patients treated with VNS for epilepsy.
      METHODS: All United Kingdom patients undergoing VNS between January 1, 1995 and
      December 31, 2010 at King's College Hospital, London were flagged through the
      national Medical Research Information Service. Analysis was performed in relation
      to all deaths occurring by December 31, 2010. Deceased patients were identified
      from the national death register, and additional information on cause and
      circumstances of death sought where appropriate to allow for classification of
      deaths. RESULTS: The cohort consisted of 466 patients, with 2993.83 person-years
      of follow-up and a median observation period of 5.9 years. Twenty-nine deaths
      occurred, 27 with the device active. SMR was 7.1 (95% confidence interval [CI]
      4.8-10.3) for the active device; 12 deaths were considered epilepsy related,
      including 10 definite or probable SUDEP and one fatal near SUDEP.
      Definite/probable and fatal near SUDEP occurred at a rate of 3.7/1,000 person
      years. SMRs decreased from 10.5 (5.6-19.5) in the first 2 years after
      implantation to 5.9 (3.7-9.5) thereafter, although CIs overlapped. SUDEP rates
      did not alter over time. SIGNIFICANCE: SMRs and SUDEP rate in this study are
      comparable to other cohorts with intractable epilepsy, with SUDEP an important
      cause of death. VNS does not appear to lower the risk of premature death overall.
      There was a clear trend with lower SMR after 2 years of implantation, although
      CIs overlapped. SUDEP rates, however, did not change.

PMID- 25580644
TI  - Response shift in severity assessment of hand eczema with visual analogue scales.
AB  - BACKGROUND: Hand eczema is a common and fluctuating disease. Visual analogue
      scales (VASs) are used to assess disease severity, both currently and when at its
      worst. However, such patient-reported outcomes may be at risk of being flawed
      owing to recall bias or response shifts. OBJECTIVE: To explore whether the
      current state of hand eczema severity affects the recollection of the eczema when
      at its worst, thus resulting in a response shift. METHODS: We utilized a dataset
      from a recent clinical trial examining nurse counselling of hand eczema patients.
      The patients assessed the disease severity currently (VASnow ) and when at its
      worst (VASworst ), both at baseline and at a 6-month follow-up. RESULTS: The
      patients who reported improvement during the course were generally more likely to
      downwardly adjust their assessment of VASworst than patients reporting unchanged
      or worsened severity (odds ratio 1.94, p = 0.017). No other determinants were
      found. CONCLUSION: Patients may downwardly adjust their assessment of worst-ever
      disease severity according to the assessment of present disease severity. Regular
      photographic documentation of the hand eczema along with the patient's self
      monitoring of symptoms as part of the treatment course could perhaps counteract
      this tendency for there to be severity habituation.

PMID- 25580646
TI  - Development of a real-time PCR assay for the quantification of Ma-LMM01-type
      Microcystis cyanophages in a natural pond.
AB  - Microcystis aeruginosa forms toxic cyanobacterial blooms throughout the world
      where its infectious phages are thought to influence host population dynamics. To
      assess the cyanophage impact on the host dynamics, we previously monitored Ma
      LMM01-type phage abundance using a real-time PCR with a primer set designed based
      on the sequence of Microcystis phage Ma-LMM01; and we estimated the phage
      infected host cell abundance. However, a recent study shows the Ma-LMM01 g91 gene
      sequence belongs to the smallest group, group III, of the three genotype groups,
      suggesting Ma-LMM01-type phage abundance was underestimated. Therefore, to re
      evaluate the effect of Ma-LMM01-type phages on their hosts, we monitored the
      abundance of Ma-LMM01-type phages using real-time PCR with a new primer set
      designed based on the sequences of genotype groups I-III. We found phage
      abundance between 10(3) and 10(4) ml(-1) using the new primer set in samples
      where previously these phages were not detected using the old primer set. The
      frequency of Ma-LMM01-type phage-infected cells to Ma-LMM01-type phage
      susceptible host cells may be as high as 30%, suggesting the phages may
      occasionally affect not only shifts in the genetic composition but also the
      dynamics of Ma-LMM01-type phage-susceptible host populations. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Phages are one of the factors that may control the ecology
      of their host blooms. Therefore, it is essential to estimate phage abundance to
      understand phage impact on host populations. A real-time PCR assay was improved
      to detect a larger range of Microcystis cyanophages in natural surroundings where
      no phages were detected using a previous method by re-designing a new primer set
      based on sequences from three Ma-LMM01-type phage genetic groups. The new method
      allows us to determine the distribution, dynamics and infection cycle of the
      phage to help understand the interaction between the phages and the hosts.

PMID- 25580647
TI  - Predictors of admission for patients presenting to the emergency department with
      renal colic.

PMID- 25580648
TI  - The New Phytologist Tansley Medal 2014.

PMID- 25580649
TI  - Introducing Tansley insights - short and timely, focussed reviews within the
      plant sciences.

PMID- 25580650
TI  - Tree physiology and bark beetles.

PMID- 25580651
TI  - When two invasion hypotheses are better than one.

PMID- 25580652
TI  - Current controversies and challenges in applying plant hydraulic techniques:
      International Workshop on Plant Hydraulic Techniques, Ulm University, Germany,
      September 2014.

PMID- 25580653
TI  - Research frontiers in drought-induced tree mortality: crossing scales and
      disciplines.

PMID- 25580654
TI  - Intercellular communication via plasmodesmata.

PMID- 25580655
TI  - Pathways for entry of livestock arboviruses into Great Britain: assessing the
      strength of evidence.
AB  - The emergence of bluetongue virus and Schmallenberg virus in Great Britain (GB)
      during the last decade has highlighted the need for understanding the relative
      importance of the various pathways of the entry of livestock arboviruses so as to
      help focus surveillance and mitigation. This study summarizes what is known for
      the main routes of entry and assesses the strength of the current evidence for
      and against. Entry through infected arthropod vectors is considered at the level
      of each life cycle stage for tick-, biting midge- and mosquito-borne viruses, and
      while there is evidence that this could happen through most tick and mosquito
      stages, strong evidence that only exists for entry through adult midges. There is
      also strong evidence that entry through immature midge stages could not happen.
      The weight of supporting evidence is strongest for importation of viraemic
      livestock including horses. While there is some indication of a common pathway
      for midge-borne viruses from sub-Saharan Africa to GB via Continental Europe,
      other factors such as maternal transmission in dogs and sheep need to be
      considered in the light of recent findings. 

PMID- 25580656
TI  - Normothermic CPB for pediatric cardiac surgery, not ready for prime time.

PMID- 25580657
TI  - Cardiac output assessment in children: playing catch-up.

PMID- 25580658
TI  - Comparing intubation performance of Bonfils fiberscope and fiberoptic
      bronchoscope in difficult pediatric airways.

PMID- 25580659
TI  - We can't tell emergence agitation from pain, yet. Reply to: Stucke and Weisman
      'Can we tell emergence agitation from pain?'.

PMID- 25580660
TI  - Response to Dr. Murphy and Dr. Ferguson regarding comment on our paper:
      retrospective evaluation of antimicrobial prophylaxis in prevention of surgical
      site infection in the pediatric population.

PMID- 25580661
TI  - Double-lumen central venous catheter for pediatric airway management in laryngeal
      papillomatosis: an old technique reborn?

PMID- 25580662
TI  - The growth rate of early DWI lesions is highly variable and associated with
      penumbral salvage and clinical outcomes following endovascular reperfusion.
AB  - BACKGROUND: The degree of variability in the rate of early diffusion-weighted
      imaging expansion in acute stroke has not been well characterized. AIM: We
      hypothesized that patients with slowly expanding diffusion-weighted imaging
      lesions would have more penumbral salvage and better clinical outcomes following
      endovascular reperfusion than patients with rapidly expanding diffusion-weighted
      imaging lesions. METHODS: In the first part of this substudy of DEFUSE 2, growth
      curves were constructed for patients with >90% reperfusion and <10% reperfusion.
      Next, the initial growth rate was determined in all patients with a clearly
      established time of symptom onset, assuming a lesion volume of 0 ml just prior to
      symptom onset. Patients who achieved reperfusion (>50% reduction in perfusion
      weighted imaging after endovascular therapy) were categorized into tertiles
      according to their initial diffusion-weighted imaging growth rates. For each
      tertile, penumbral salvage [comparison of final volume to the volume of perfusion
      weighted imaging (Tmax > 6 s)/diffusion-weighted imaging mismatch prior to
      endovascular therapy], favorable clinical response (National Institutes of Health
      Stroke Scale improvement of >=8 points or 0-1 at 30 days), and good functional
      outcome (90-day modified Rankin score of <=2) were calculated. A multivariate
      model assessed whether infarct growth rates were an independent predictor of
      clinical outcomes. RESULTS: Sixty-five patients were eligible for this study; the
      median initial growth rate was 3.1 ml/h (interquartile range 0.7-10.7). Target
      mismatch patients (n = 42) had initial growth rates that were significantly
      slower than the growth rates in malignant profile (n = 9 patients, P < 0.001). In
      patients who achieved reperfusion (n = 38), slower early diffusion-weighted
      imaging growth rates were associated with better clinical outcomes (P < 0.05) and
      a trend toward more penumbral salvage (n = 31, P = 0.103). A multivariate model
      demonstrated that initial diffusion-weighted imaging growth rate was an
      independent predictor of achieving a 90-day modified Rankin score of <=2.
      CONCLUSIONS: The growth rate of early diffusion-weighted imaging lesions in acute
      stroke patients is highly variable; malignant profile patients have higher growth
      rates than patients with target mismatch. A slower rate of early diffusion
      weighted imaging growth is associated with a greater degree of penumbral salvage
      and improved clinical outcomes following endovascular reperfusion.

PMID- 25580663
TI  - Decreased FEV1 % in asthmatic adults in Scottish homes with high Environmental
      Relative Moldiness Index values.
AB  - BACKGROUND: Exposures to indoor biological contaminants have been implicated in
      asthma's aetiology but their effect on lung function is not well quantified.
      OBJECTIVE: The aim of this cross-sectional study of non-smoking, asthmatic adults
      in Scotland was to determine the correlation between the results from a standard
      spirometry test, forced expiratory volume in one-second percent (FEV1 %), and
      quantitative estimates of some biological exposures. METHODS: A population (n =
      55) of non-smoking, adult asthmatics in Scotland was included in this study and
      each completed a questionnaire that allowed the determination of the Asthma
      Control Questionnaire scores (ACQ) and St. George's Respiratory Questionnaire
      scores (SGRQ), as well as corticosteroid use. Spirometry testing was completed
      and the pre-bronchodilator FEV1 % value calculated. At about the same time, floor
      dust samples were collected in the living room and in the bedroom. These dust
      samples were analysed for mould contamination, as described by the Environmental
      Relative Moldiness Index (ERMI) values and by (1, 3)-beta-D-glucan
      concentrations, for endotoxin, and for dust mite, cat, and dog allergen
      concentrations. The asthmatics' FEV1 % values were tested for correlation
      (Pearson) to questionnaire-based estimates of health. Also, each biological
      exposure was tested for correlation (Pearson) to the FEV1 % values. RESULTS: FEV1
      % results were correlated with ACQ scores (rho -0.586, P < 0.001), SGRQ scores
      (rho -0.313, P = 0.020), and weakly with corticosteroid use (rho -0.221, P =
      0.105). The ERMI values in the homes (average 5.3) were significantly correlated
      with FEV1 % values (rho -0.378, P = 0.004). There was no correlation between FEV1
      % and concentrations of endotoxin, (1, 3)-beta-D-glucan, or any of the allergens.
      CONCLUSION AND CLINICAL RELEVANCE: Although these results do not prove that mould
      exposures caused the deficit in lung function observed in this study, it might be
      advisable for asthmatics to avoid high ERMI environments.

PMID- 25580664
TI  - Molecular detection identified a type six secretion system in Campylobacter
      jejuni from various sources but not from human cases.
AB  - AIM: To determine the presence of the T6SS in Campylobacter jejuni from diverse
      sources. METHODS AND RESULTS: The recently identified type VI secretion system
      (T6SS) is a bacterial injection machinery that plays a role in virulence,
      symbiosis, bacterial interactions and environmental stress responses. This system
      has been recently discovered in the major enteric pathogen Camp. jejuni. In this
      study, we used multiplex PCR (mPCR), based on conserved genetic markers of the
      T6SS, to screen 366 Pakistani Camp. jejuni isolates from humans, poultry, cattle,
      wildlife or waste-water sources. We identified the T6SS in isolates from all of
      these sources except humans. The overall prevalence of the T6SS among the
      isolates was 17/366 (4.6%) and the T6SS positive isolates clustered into four
      different groups. Transcription of the T6SS genes, determined using RT-PCR, was
      observed in bacteria cultured at 37 or 42 degrees C but not in 37 degrees C
      cultures adjusted to pH3. CONCLUSIONS: Campylobacter jejuni isolates harbouring
      T6SS markers genes were identified in livestock and non-livestock sources but in
      this study we did not identify human diarrhoeal isolates which possessed the
      T6SS. We demonstrated down-regulation of T6SS in an acidic environment.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study questions the role of the T6SS
      in human diarrhoeal disease. Moreover this study did not identify a clear
      association of Camp. jejuni isolates harbouring T6SS with any of the niches
      tested. Our study highlights the need to establish the role of the T6SS in
      environmental survival or virulence.

PMID- 25580665
TI  - Effect of subcutaneous insulin detemir on glucose flux and lipolysis during
      hyperglycaemia in people with type 1 diabetes.
AB  - AIMS: To investigate, using a novel non-steady-state protocol, the differential
      effects of subcutaneous (s.c.) detemir and NPH insulin on glucose flux and lipid
      metabolism after insulin withdrawal. METHODS: After a period of insulin
      withdrawal resulting in whole-blood glucose concentration of 7 mmol/l, 11
      participants (five men, mean age 41.0 years, mean body mass index 25 kg/m(2))
      with type 1 diabetes (mean glycated haemoglobin concentration 57 mmol/mol, mean
      diabetes duration 14 years) received 0.5 units per kg body weight s.c. insulin
      detemir or NPH insulin in random order. Stable isotopes of glucose and glycerol
      were infused intravenously throughout the study protocol. RESULTS: Glucose
      concentration decreased after insulin treatment as a result of suppression of
      endogenous glucose production, which occurred to a similar extent with both
      detemir and NPH insulin. The rate of glucose disappearance (Rd) was not increased
      significantly with either type of insulin. When the effect of detemir and NPH
      insulin on glucose flux at glucose concentrations between 9 and 6 mmol/l was
      examined, glucose rate of appearance (Ra) was similar with the two insulins;
      however, glucose Rd was greater with NPH insulin than with detemir at glucose
      concentrations of 8.0, 8.5, 7.0 and 6.0 mmol/l (p < 0.05) The percentage change
      in glycerol Ra, a measure of lipolysis, was greater in the NPH group than in the
      detemir group (p = 0.04). CONCLUSIONS: The results of the study are consistent
      with the hypothesis that detemir has a lesser effect on the periphery, as
      evidenced by a lesser effect on peripheral glucose uptake at specific glucose
      concentrations.

PMID- 25580666
TI  - Hydrogen export from intertidal cyanobacterial mats: sources, fluxes and the
      influence of community composition.
AB  - Microbial mats from marine intertidal settings have been reported to release
      significant quantities of H2 , in a unique trait among other mats and microbial
      communities. However, the H2 source and ecophysiological mechanisms that enable
      its export are not well understood. We examined H2 accumulation and export in
      three types of greenhouse-reared mats, from the intertidal region of Guerrero
      Negro, Mexico, and kept under natural light-dark conditions and wetting and
      drying cycles simulating low-, mid- and high-tidal height periodicity. All mats
      released H2 reproducibly and sustainably for 1.5 years. Net H2 export took place
      in a pulsed daily manner, starting after dusk, and waning in the morning, as
      photosynthesis resumed. Mid- and low-tidal mats developed high concentrations,
      capable of sustaining export fluxes that represented 2-4% of the water split
      through primary productivity. Neither N2 fixation nor direct photolytic
      hydrogenogenesis was significant to this H2 export, which was fermentative in
      origin, variable among mats, originating from cyanobacterial photosynthate.
      Analyses of community composition by pyrosequencing of 16S rRNA and hoxH genes
      indicate that filamentous non-heterocystous cyanobacteria (e.g. Lyngbya,
      Microcoleus) were important in the process of H2 export, as was the relatively
      low abundance and activity of methanogens and sulfate reducers. 

PMID- 25580667
TI  - Impact of bariatric surgery on physical functioning in obese adults.
AB  - Obesity is associated with a profound impairment in the ability to perform the
      basic physical activities required for everyday function. This impacts on quality
      of life and contributes to disability. Bariatric surgery leads to weight loss and
      metabolic improvements in severe obesity; however, less is known about its effect
      on physical functioning. This narrative review summarizes current evidence on the
      effect of bariatric surgery on this outcome with a consideration of the
      mechanisms involved. Nine longitudinal observational studies reporting objective
      measures of physical functioning were identified. Inclusion criteria, follow-up
      time and outcomes reported varied considerably between studies and sample sizes
      were small. They all showed a significant improvement in performance following
      surgery despite variations in baseline patient characteristics. Additionally, six
      studies were found in which subjects were subjected to exercise testing
      protocols. Performance of the test protocol improved in all. Where reported, peak
      oxygen uptake related to body weight improved; however, absolute values were
      either unchanged or decreased. In conclusion, observational evidence suggests
      that patients' physical functioning improves following bariatric surgery. More
      evidence is required regarding mechanisms involved; however, it may be due to
      improved efficiency in performing activities as opposed to absolute improvements
      in cardiorespiratory or muscle function. 

PMID- 25580668
TI  - What have we learned from a questionnaire survey of citizens and doctors both
      inside and outside Fukushima?: survey comparison between 2011 and 2013.
AB  - The disaster at the Fukushima Daiichi Nuclear Power Plant (FDNPP) remains
      unresolved because the estimated time to decommission a nuclear reactor appears
      to be approximately 40 years. The number of workers exposed to radiation doses
      ranging from 1 to 100 mSv continues to increase. To understand the accident
      progression at Fukushima and to anticipate what we should do in the future for
      occupational and environmental health, we performed a survey of citizens and
      doctors who lived inside and outside Fukushima in 2011 and 2013. In a comparison
      of these 2 years, the citizens inside Fukushima continue to suffer anxiety,
      although those living outside Fukushima tended to feel less anxious. Medical
      students who had recently studied radiation biology showed much less ongoing
      anxiety compared with other groups, suggesting that learning about the effects of
      radiation is essential to understanding one's own circumstances objectively and
      correctly. The lack of trust in the government and in the Tokyo Electric Power
      Company (TEPCO) in 2013 remains high in all groups. Therefore, long-term
      forthright explanations from the government, TEPCO, and radiation experts are
      indispensable not only to establish trust with people but also to alleviate
      psychological stress. 

PMID- 25580669
TI  - Pulsed radiofrequency for chronic intractable lumbosacral radicular pain: a six
      month cohort study.
AB  - BACKGROUND AND OBJECTIVES: There is little evidence concerning the medical
      management of lumbosacral radicular pain. The prognosis for patients suffering
      pain for more than 3 months is poor. Pulsed radiofrequency (PRF) treatment of the
      dorsal root ganglion (DRG) has been suggested as a minimally invasive treatment.
      We studied the effect on pain and quality of life of PRF treatment of the DRG in
      patients with chronic, severe lumbosacral radicular pain. METHODS: Patients with
      lumbosacral radicular pain were screened to select a homogeneous population. PRF
      treatment of the DRG was performed at L5 or S1. Evaluation was carried out at 6
      weeks, 3 months, and 6 months. Pain reduction and "fully recovered" or "much
      improvement," in terms of the global perceived effect, were the primary outcomes.
      Quality of life (RAND-36), disability (Oswestry Disability Index), and the
      neuropathic pain scales leeds assessment of neuropathic symptoms and signs
      (LANSS) and DN4 were registered at each time point. Medication use was scored
      with the Medication Quantification Scale. RESULTS: Out of 461 screened patients,
      65 were included. According to the intention to treat analysis, clinical success
      was achieved in 56.9%, 52.3%, and 55.4% of the patients at respectively 6 weeks,
      3 months, and 6 months. DN4, Oswestry Disability Index and physical component for
      the RAND-36 quality of life improved significantly while the mental component
      remained unchanged. The number of patients on opioids was reduced. CONCLUSIONS:
      PRF treatment of the DRG may be considered for patients with chronic, severe
      lumbosacral radicular pain refractory to conventional medical management.

PMID- 25580670
TI  - What the Eczema Area and Severity Index score tells us about the severity of
      atopic dermatitis: an interpretability study.
AB  - BACKGROUND: The Eczema Area and Severity Index (EASI) is an investigator-assessed
      instrument measuring the severity of clinical signs in atopic dermatitis (AD).
      The EASI was identified as one of the best-validated outcome measures for AD;
      however, no previous studies address how to interpret the EASI score for clinical
      use. OBJECTIVES: To evaluate the interpretability and the ease of use of the
      EASI. METHODS: A retrospective analysis of paediatric and adult patients with AD
      was performed. Interpretability was evaluated by stratifying the EASI scores
      according to the Investigator's Global Assessment. The severity strata displaying
      the highest kappa coefficient of agreement were then selected as the recommended
      EASI band. The time to administer the EASI was recorded in a subgroup of
      patients. RESULTS: The suggested severity strata for the EASI are as follows: 0 =
      clear; 0.1-1.0 = almost clear; 1.1-7.0 = mild; 7.1-21.0 = moderate; 21.1-50.0 =
      severe; 50.1-72.0 = very severe (kappa = 0.75). The EASI was also found to be
      acceptable in terms of ease of use, with assessments by trained investigators
      taking approximately 6 min. CONCLUSIONS: Our study provides the first guide for
      interpreting the EASI score. It enables translation of the EASI numerical output
      into an AD global severity state that should be more meaningful to providers and
      patients. Along with a short administration time, the EASI demonstrates adequate
      feasibility, further supporting its use in clinical trials.

PMID- 25580671
TI  - Screening for psychological and mental health difficulties in young people who
      offend: a systematic review and decision model.
AB  - BACKGROUND: There is policy interest in the screening and treatment of mental
      health problems in young people who offend, but the value of such screening is
      not yet known. OBJECTIVES: To assess the diagnostic test accuracy of screening
      measures for mental health problems in young people who offend; to evaluate the
      clinical effectiveness and cost-effectiveness of screening and treatment; to
      model estimates of cost; to assess the evidence base for screening against UK
      National Screening Committee criteria; and to identify future research
      priorities. DATA SOURCES: In total, 25 electronic databases including MEDLINE,
      PsycINFO, EMBASE and The Cochrane Library were searched from inception until
      April 2011. Reverse citation searches of included studies were undertaken and
      reference list of included studies were examined. REVIEW METHODS: Two reviewers
      independently examined titles and abstracts and extracted data from included
      studies using a standardised form. The inclusion criteria for the review were (1)
      population - young offenders (aged 10-21 years); (2) intervention/instrument -
      screening instruments for mental health problems, implementation of a screening
      programme or a psychological or pharmacological intervention as part of a
      clinical trial; (3) comparator - for diagnostic test accuracy studies, any
      standardised diagnostic interview; for trials, any comparator; (4) outcomes -
      details of diagnostic test accuracy, mental health outcomes over the short or
      longer term or measurement of cost data; and (5) study design - for diagnostic
      test accuracy studies, any design; for screening programmes, randomised
      controlled trials or controlled trials; for clinical effectiveness studies,
      randomised controlled trials; for economic studies, economic evaluations of
      screening strategies or interventions. RESULTS: Of 13,580 studies identified,
      nine, including eight independent samples, met the inclusion criteria for the
      diagnostic test accuracy and validity of screening measures review. Screening
      accuracy was typically modest. No studies examined the clinical effectiveness of
      screening, although 10 studies were identified that examined the clinical
      effectiveness of interventions for mental health problems. There were too few
      studies to make firm conclusions about the clinical effectiveness of treatments
      in this population. No studies met the inclusion criteria for the assessment of
      the cost-effectiveness of screening or treatment. An exemplar decision model was
      developed for depression, which identified a number of the likely key drivers of
      uncertainty, including the prevalence of unidentified mental health problems, the
      severity of mental health problems and their relationship to generic measures of
      outcome and the impact of treatment on recidivism. The information evaluated as
      part of the review was relevant to five of the UK National Screening Committee
      criteria. On the basis of the above results, none of the five criteria was met.
      LIMITATIONS: The conclusions of the review are based on limited evidence.
      Conclusions are tentative and the decision model should be treated as an
      exemplar. CONCLUSIONS: Evidence on the clinical effectiveness and cost
      effectiveness of screening for mental health problems in young people who offend
      is currently lacking. Future research should consider feasibility trials of
      clinical interventions to establish important parameters ahead of conducting
      definitive trials. Future diagnostic studies should compare the diagnostic test
      accuracy of a range of screening instruments, including those recommended for use
      in the UK in this population. These studies should be designed to reduce the
      decision uncertainty identified by the exemplar decision model. REGISTRATION:
      This study is registered as PROSPERO CRD42011001466. FUNDING: The National
      Institute for Health Research Health Technology Assessment programme.

PMID- 25580672
TI  - Assessing psychopathy among justice involved adolescents with the PCL:YV: an item
      response theory examination across gender.
AB  - This study used an item response theory (IRT) model and a large adolescent sample
      of justice involved youth (N = 1,007, 38% female) to examine the item functioning
      of the Psychopathy Checklist-Youth Version (PCL: YV). Items that were most
      discriminating (or most sensitive to changes) of the latent trait (thought to be
      psychopathy) among adolescents included "glibness/superficial charm," "lack of
      remorse," and "need for stimulation," whereas items that were least
      discriminating included "pathological lying," "failure to accept responsibility,"
      and "lacks goals." The items "impulsivity" and "irresponsibility" were the most
      likely to be rated high among adolescents, whereas "parasitic lifestyle," and
      "glibness/superficial charm" were the most likely to be rated low. Evidence of
      differential item functioning (DIF) on 4 of the 13 items was found between boys
      and girls. "Failure to accept responsibility" and "impulsivity" were endorsed
      more frequently to describe adolescent girls than boys at similar levels of the
      latent trait, and vice versa for "grandiose sense of self-worth" and "lacks
      goals." The DIF findings suggest that 4 PCL: YV items function differently
      between boys and girls.

PMID- 25580673
TI  - Daily shame and hostile irritability in adolescent girls with borderline
      personality disorder symptoms.
AB  - Recent theoretical and empirical work suggests that adults with borderline
      personality disorder (BPD) have difficulty regulating both shame and anger, and
      that these emotions may be functionally related in clinically relevant ways
      (e.g., Schoenleber & Berenbaum, 2012b). The covariation of shame with anger
      related emotions has important clinical implications for interventions targeting
      shame and uncontrolled anger in BPD. However, no studies have examined shame,
      anger, and their covariation in adolescents who may be at risk for developing
      BPD. Therefore, this study focuses on associations between BPD symptoms and
      patterns of covariation between daily experiences of shame and anger-related
      affects (i.e., hostile irritability) in a community sample of adolescent girls
      using ecological momentary assessment. Multilevel models revealed that girls with
      greater BPD symptoms who reported greater mean levels of shame across the week
      also tended to report more hostile irritability, even after controlling for
      guilt. Additionally, examination of within-person variability showed that girls
      with greater BPD symptoms reported more hostile irritability on occasions when
      they also reported greater concurrent shame, but this was only the case in girls
      of average socioeconomic status (i.e., those not receiving public assistance).
      Unlike shame, guilt was not associated with hostile irritability in girls with
      greater BPD symptoms. Results suggest that shame may be a key clinical target in
      the treatment of anger-related difficulties among adolescent girls with BPD
      symptoms.

PMID- 25580675
TI  - Emotional reactivity to social rejection versus a frustration induction among
      persons with borderline personality features.
AB  - This laboratory study examined the emotional reactivity of persons with
      heightened borderline personality (BP) features to a social rejection stressor.
      Participants with high levels of BP features (n = 43) and controls with low
      levels of BP features (n = 67) were randomly assigned to a condition involving
      negative evaluation and social rejection based on personal characteristics, or to
      a condition involving a frustrating arithmetic task and negative evaluation based
      on performance. Hypotheses were that the high-BP individuals would demonstrate
      greater increases in negative emotions, shame, and anger in response to the
      social rejection/negative evaluation stressor, compared with the frustrating
      arithmetic task. The high-BP group showed significant increases in negative
      emotions in both conditions, significant increases in shame only in the
      frustrating arithmetic task, and significant increases in hostility only in the
      social rejection condition. In contrast, low-BP controls showed significant
      increases in negative emotions generally in the frustrating arithmetic condition
      and shame specifically in the social rejection condition. These findings
      highlight the emotion and context-specific nature of emotional reactivity in
      relation to BP features.

PMID- 25580676
TI  - Structure of the submonolayer of ethanol adsorption on a vapor/fused silica
      interface studied with sum frequency vibrational spectroscopy.
AB  - Sum-frequency vibrational spectroscopy in the CH and OH stretch region was used
      to study ethanol adsorption on fused silica from vapor of different ethanol
      partial pressures. It was found that the adsorbed ethanol molecules were oriented
      with their methyl group tilted away from the surface normal by an average angle
      of ~45 degrees  at low ethanol vapor pressures and ~39 degrees  when approaching
      saturated vapor pressure. The spectral change with ethanol vapor pressure and the
      deduced adsorption isotherm show that ethanol molecules have two distinct
      adsorption sites on silica: One is the silanol group site to which an ethanol
      molecule can be strongly hydrogen-bonded, and the other is the siloxane (Si-O-Si)
      group site to which an ethanol molecule can be weakly bonded. The presence of
      water in vapor significantly reduced the surface coverage of ethanol on silica
      due to competitive adsorption between ethanol and water. 

PMID- 25580674
TI  - Generalizability of pharmacological and psychotherapy clinical trial results for
      borderline personality disorder to community samples.
AB  - The present study sought to quantify the generalizability of clinical trial
      results in individuals with a Diagnostic and Statistical Manual of Mental
      Disorders, fourth edition (DSM-IV) diagnosis of borderline personality disorder
      (BPD) to a large representative community sample. Data were derived from the 2004
      2005 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a
      large nationally representative sample of 34,653 adults from the United States
      population. We applied a standard set of exclusion criteria representative of
      pharmacological and psychotherapy clinical trials to all adults with a DSM-IV
      diagnosis of BPD (n = 2,231). Our aim was to assess how many participants with
      BPD would not fulfill typical eligibility criteria. We found that more than 7 of
      10 respondents in a typical pharmacological efficacy trial and more than 5 of 10
      participants in a typical psychotherapy efficacy trial would have been excluded
      by at least 1 criterion. Having a current history of alcohol or drug use disorder
      and a lifetime history of bipolar disorder explained a large proportion of
      ineligibility in both pharmacological and psychotherapy efficacy trials. Clinical
      trials should carefully consider the impact of exclusion criteria on the
      generalizability of their results. As required by CONSORT guidelines, reporting
      exclusion rate estimate and reasons of eligibility should be mandatory in both
      clinical trials and meta-analyses. As treatment trials of borderline personality
      disorder move from efficacy to effectiveness to better inform clinical practice,
      the eligibility rate must be increased by imposing less stringent eligibility
      criteria to allow for more generalizable results.

PMID- 25580677
TI  - Quantitative characterization of nonspecific self- and hetero-interactions of
      proteins in nonideal solutions via static light scattering.
AB  - The dependence of static light scattering upon the compositions of solutions
      including hen egg white ovalbumin, hen egg white ovomucoid, ribonuclease A, and
      binary mixtures of these proteins at total concentrations of up to about 40 g/L
      were measured at different values of the pH and ionic strength. At the pH values
      of measurement, ovalbumin and ovomucoid have a net negative charge and
      ribonuclease A has a net positive charge. The observed dependence of scattering
      intensity upon solution composition may be accounted for by an extension of
      previously formulated equivalent hard particle models that allows for the
      presence of both repulsive interactions between like species and attractive
      interactions between unlike species in mixtures of positively and negatively
      charged proteins. 

PMID- 25580678
TI  - Efficacy and Safety of a New Technique of Conversion from Temporary to Tunneled
      Central Venous Catheters.
AB  - The usually applied conversion technique from temporary to tunneled central
      venous catheters (CVCs) using the same venous insertion site requires a peel-away
      sheath. We propose a conversion technique without peel-away sheath: a guide wire
      is advanced through the existing temporary CVC; then, a subcutaneous tunnel is
      created from the exit to the venotomy site. After removing the temporary CVC, the
      tunneled one is advanced along the guide wire. The study group included all
      patients requiring a catheter conversion from January 2012 to June 2014; the
      control group included incident patients who had received de novo placement of
      tunneled CVCs from January 2010 to December 2011. The main outcome measures were
      technical success and immediate complications. Seventy-two tunneled catheters (40
      with our conversion technique and 32 with the traditional one) were placed in 72
      patients. The technical success was 95% in the study group and 75% in the
      controls (p = 0.019). The immediate complications were one bleeding in the study
      group (2.5%) and one air embolism, one pneumothorax, and four bleedings (18.7%)
      in the controls (p = 0.039). Conversion from temporary to tunneled CVC using a
      guide wire and without a peel-away sheath is an effective and safe procedure. 

PMID- 25580679
TI  - Multidisciplinary sliding-gantry CT: from concept to reality.
AB  - Sliding-gantry computed tomography offers an interesting variety of treatment
      options for emergency radiology and clinical routine. The Frankfurt 2-room
      installation provides an interdisciplinary, multifunctional, and cost-effective
      concept. It is based on a magnetically sealed rail system for the permanent
      movement of the gantry between 2 adjacent rooms with fixed-mounted tables. In
      case of emergency or intensive care patients, routine scanning can be performed
      in room 1 until computed tomography diagnosis is required in room 2 and can then
      be continued in room 1 again. Moreover, this concept allows the simultaneous
      handling of 2 emergency patients. 

PMID- 25580680
TI  - Genotoxicity of metal oxide nanomaterials: review of recent data and discussion
      of possible mechanisms.
AB  - Nanotechnology has rapidly entered into human society, revolutionized many areas,
      including technology, medicine and cosmetics. This progress is due to the many
      valuable and unique properties that nanomaterials possess. In turn, these
      properties might become an issue of concern when considering potentially
      uncontrolled release to the environment. The rapid development of new
      nanomaterials thus raises questions about their impact on the environment and
      human health. This review focuses on the potential of nanomaterials to cause
      genotoxicity and summarizes recent genotoxicity studies on metal oxide/silica
      nanomaterials. Though the number of genotoxicity studies on metal oxide/silica
      nanomaterials is still limited, this endpoint has recently received more
      attention for nanomaterials, and the number of related publications has
      increased. An analysis of these peer reviewed publications over nearly two
      decades shows that the test most employed to evaluate the genotoxicity of these
      nanomaterials is the comet assay, followed by micronucleus, Ames and chromosome
      aberration tests. Based on the data studied, we concluded that in the majority of
      the publications analysed in this review, the metal oxide (or silica)
      nanoparticles of the same core chemical composition did not show different
      genotoxicity study calls (i.e. positive or negative) in the same test, although
      some results are inconsistent and need to be confirmed by additional experiments.
      Where the results are conflicting, it may be due to the following reasons: (1)
      variation in size of the nanoparticles; (2) variations in size distribution; (3)
      various purities of nanomaterials; (4) variation in surface areas for
      nanomaterials with the same average size; (5) differences in coatings; (6)
      differences in crystal structures of the same types of nanomaterials; (7)
      differences in size of aggregates in solution/media; (8) differences in assays;
      (9) different concentrations of nanomaterials in assay tests. Indeed, due to the
      observed inconsistencies in the recent literature and the lack of adherence to
      appropriate, standardized test methods, reliable genotoxicity assessment of
      nanomaterials is still challenging. 

PMID- 25580682
TI  - Partitioning of humic acids between aqueous solution and hydrogel. 3.
      Microelectrodic dynamic speciation analysis of free and bound humic metal
      complexes in the gel phase.
AB  - The hydrogel/water partitioning of the various species in the cadmium(II)/soil
      humic acid (HA) system is studied for two types of gel, using in situ
      microelectrodic voltammetry. Under the conditions of this work, with HA particles
      of ca. 25 and 125 nm radius, the CdHA complex is shown to be close to nonlabile
      toward a 12.5 MUm radius microelectrode. This implies that its kinetic
      contribution to Cd(2+) reduction at the medium/microelectrode interface is
      practically negligible. The polyacrylamide (PAAm) gels equilibrate with the
      aqueous medium under significant sorption of HA at the gel backbone/gel medium
      interface, which in turn leads to induced sorption of Cd(II) in the form of
      immobilized gel-bound CdHA. The rather high total Cd content of the PAAm gel
      suggests that the binding of Cd(2+) by the hydrophobically gel-bound HA is
      stronger than that for dispersed HA particles. Still, the intraparticulate
      speciation of Cd(II) over Cd(2+) and CdHA corresponds to an intrinsic stability
      constant similar to that for simple monocarboxylate ligands such as acetate.
      Alginate gels are negatively charged, and their free [Cd(aq)(2+)] is higher than
      that in the medium by the corresponding Donnan coefficient. On top of that,
      Cd(2+) is specifically sorbed by the gel backbone/gel medium interface to reach
      accumulation factors as high as a few tens. HA and CdHA accumulate in the outer
      20 MUm film of gel at the gel/water interface of both gels, but they do not
      penetrate into the bulk of the alginate gel. Overall, the gel/water interface
      dictates drastic changes in the speciation of Cd/HA as compared to the aqueous
      medium, with distinct features for each individual type of gel. The results have
      broad significance, for example, for predictions of reactivity and
      bioavailability of metal species which inherently involve partitioning and
      diffusion into diverse gel layers such as biointerfacial cell walls, biofilm
      matrices, and mucous membranes.

PMID- 25580681
TI  - IL-33 facilitates oncogene-induced cholangiocarcinoma in mice by an interleukin-6
      sensitive mechanism.
AB  - Cholangiocarcinoma (CCA) is a lethal hepatobiliary neoplasm originating from the
      biliary apparatus. In humans, CCA risk factors include hepatobiliary inflammation
      and fibrosis. The recently identified interleukin (IL)-1 family member, IL-33,
      has been shown to be a biliary mitogen which also promotes liver inflammation and
      fibrosis. Our aim was to generate a mouse model of CCA mimicking the human
      disease. Ectopic oncogene expression in the biliary tract was accomplished by the
      Sleeping Beauty transposon transfection system with transduction of
      constitutively active AKT (myr-AKT) and Yes-associated protein. Intrabiliary
      instillation of the transposon-transposase complex was coupled with lobar bile
      duct ligation in C57BL/6 mice, followed by administration of IL-33 for 3
      consecutive days. Tumors developed in 72% of the male mice receiving both
      oncogenes plus IL-33 by 10 weeks but in only 20% of the male mice transduced with
      the oncogenes alone. Tumors expressed SOX9 and pancytokeratin (features of CCA)
      but were negative for HepPar1 (a marker of hepatocellular carcinoma). Substantive
      overlap with human CCA specimens was revealed by RNA profiling. Not only did IL
      33 induce IL-6 expression by human cholangiocytes but it likely facilitated tumor
      development in vivo by an IL-6-sensitive process as tumor development was
      significantly attenuated in Il-6(-/-) male animals. Furthermore, tumor formation
      occurred at a similar rate when IL-6 was substituted for IL-33 in this model.
      CONCLUSION: The transposase-mediated transduction of constitutively active AKT
      and Yes-associated protein in the biliary epithelium coupled with lobar
      obstruction and IL-33 administration results in the development of CCA with
      morphological and biochemical features of the human disease; this model
      highlights the role of inflammatory cytokines in CCA oncogenesis.

PMID- 25580683
TI  - 2-Keto-D-gluconate-yielding membrane-bound D-glucose dehydrogenase from
      Arthrobacter globiformis C224: purification and characterization.
AB  - Glucose dehydrogenase (GlcDH) is the rate-limiting catalyst for microbial
      conversion of glucose to the important organic acid 2-ketogluconic acid (2KGlcA).
      In this study, a D-glucose dehydrogenase was purified from the industrial 2KGlcA
      producer Arthrobacter globiformis C224. After four purification steps, the GlcDH
      was successfully purified over 180 folds and specific activity of 88.1 U/mg. A
      single protein band of 87 kDa was detected by SDS-PAGE. The purified GlcDH had
      the broad substrate specificity with the Km values for D-glucose, D-xylose, D
      galactose and maltose of 0.21 mM, 0.34 mM, 0.46 mM and 0.59 mM, respectively. The
      kinetic studies proved that A. globiformis GlcDH followed the ping-pong kinetic
      mechanism. The GlcDH showed an optimum catalytic activity at pH 5.0 and 45 
      degrees C with the stable activity at temperature of 20-40  degrees C and pH of
      6.0-7.0. Organic solvents, metal ions or EDTA could significantly influence the
      GlcDH activity to different degrees. 

PMID- 25580684
TI  - Inhibition of the NF-kappaB signaling pathway by a novel heterocyclic curcumin
      analogue.
AB  - In this study a series of curcumin analogues were evaluated for their ability to
      inhibit the activation of NF-kappaBeta, a transcription factor at the crossroads
      of cancer-inflammation. Our novel curcumin analogue BAT3 was identified to be the
      most potent NF-kappaB inhibitor and EMSA assays clearly showed inhibition of NF
      kappaB/DNA-binding in the presence of BAT3, in agreement with reporter gene
      results. Immunofluorescence experiments demonstrated that BAT3 did not seem to
      prevent nuclear p65 translocation, so our novel analogue may interfere with NF
      kappaB/DNA-binding or transactivation, independently of IKK2 regulation and NF
      kappaB-translocation. Gene expression studies on endogenous NF-kappaB target
      genes revealed that BAT3 significantly inhibited TNF-dependent transcription of
      IL6, MCP1 and A20 genes, whereas an NF-kappaB independent target gene heme
      oxygenase-1 remained unaffected. In conclusion, we demonstrate that BAT3 seems to
      inhibit different cancer-related inflammatory targets in the NF-kappaB signaling
      pathway through a different mechanism in comparison to similar analogues,
      previously reported. 

PMID- 25580685
TI  - Development of sulfadiazine-decorated PLGA nanoparticles loaded with 5
      fluorouracil and cell viability.
AB  - The aim of this work was to synthesize sulfadiazine-poly(lactide-co-glycolide)
      (SUL-PLGA) nanoparticles (NPs) for the efficient delivery of 5-fluorouracil to
      cancer cells. The SUL-PLGA conjugation was assessed using FTIR, 1H-NMR, 13C-NMR,
      elemental analysis and TG and DTA analysis. The SUL-PLGA NPs were characterized
      using transmission and scanning electron microscopy and dynamic light scattering.
      Additionally, the zeta potential, drug content, and in vitro 5-FU release were
      evaluated. We found that for the SUL-PLGA NPs, Dh = 114.0 nm, ZP = -32.1 mV and
      the encapsulation efficiency was 49%. The 5-FU was released for up to 7 days from
      the NPs. Cytotoxicity evaluations of 5-FU-loaded NPs (5-FU-SUL-PLGA and 5-FU
      PLGA) on two cancer cell lines (Caco-2, A431) and two normal cell lines
      (fibroblast, osteoblast) were compared. Higher cytotoxicity of 5-FU-SUL-PLGA NPs
      were found to both cancer cell lines when compared to normal cell lines,
      demonstrating that the presence of SUL could significantly enhance the
      cytotoxicity of the 5-FU-SUL-PLGA NPs when compared with 5-FU-PLGA NPs. Thus, the
      development of 5-FU-SUL-PLGA NPs to cancer cells is a promising strategy for the
      5-FU antitumor formulation in the future. 

PMID- 25580686
TI  - The role of selected flavonols in tumor necrosis factor-related apoptosis
      inducing ligand receptor-1 (TRAIL-R1) expression on activated RAW 264.7
      macrophages.
AB  - Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptors (TRAIL-R) are
      an important factor of apoptosis in cancer cells. There are no data about the
      effect of flavonols on the receptor expression on a surface of macrophage like
      cells. In this study, the expression level of TRAIL-R1 on murine RAW264.7
      macrophages in the presence of selected flavonols: galangin, kaempferol,
      kaempferide and quercetin, which differ from their phenyl ring substituents, were
      studied. The expression of TRAIL-R1 death receptors on non-stimulated and
      lipopolysaccharide (LPS)-stimulated macrophages was determined using flow
      cytometry. The results suggested that compounds being tested can modulate TRAIL
      R1 expression and can enhance TRAIL-mediated apoptosis. 

PMID- 25580687
TI  - Phenolic profiling of the South American "Baylahuen" tea (Haplopappus spp.,
      Asteraceae) by HPLC-DAD-ESI-MS.
AB  - The aerial parts of several Haplopappus species (Asteraceae), known under the
      common name "baylahuen", are used as herbal teas in Chile and Argentina. In
      Chile, "baylahuen" comprises H. multifolius, H. taeda, H. baylahuen and H.
      rigidus. Little is known about the chemical identity of the infusion constituents
      in spite of widespread consumption. The aim of the present work was the
      characterization of phenolics occurring in the infusions and methanol extracts of
      "baylahuen" by HPLC-DAD-ESI-MS. A simple HPLC-DAD-ESI-MS method was developed for
      the fast identification and differentiation of Haplopappus spp. used as a tea
      source, based on the phenolics from the tea and methanol extracts. Some 27
      phenolics were tentatively identified in the infusions and methanol extract,
      including 10 caffeoyl quinic and feruloyl quinic acid derivatives and 17
      flavonoids. The HPLC patterns of the Haplopappus tea and methanol extract allow a
      clear differentiation at the species level. The occurrence of hydroxycinnamic
      acid derivatives and flavonoids can explain the reputed nutraceutical and health
      beneficial properties of this herbal tea. 

PMID- 25580688
TI  - Activity of alkaloids on peptic ulcer: what's new?
AB  - Peptic ulcer is a common disease characterized by lesions that affect the mucosa
      of the esophagus, stomach and/or duodenum, and may extend into the muscular layer
      of the mucosa. Natural products have played an important role in the process of
      development and discovery of new drugs, due to their wide structural diversity
      and present, mostly specific and selective biological activities. Among natural
      products the alkaloids, biologically active secondary metabolites, that can be
      found in plants, animals or microorganisms stand out. The alkaloids are compounds
      consisting of a basic nitrogen atom that may or may not be part of a heterocyclic
      ring. This review will describe 15 alkaloids with antiulcer activity in animal
      models and in vitro studies. 

PMID- 25580689
TI  - The Lectin Frontier Database (LfDB), and data generation based on frontal
      affinity chromatography.
AB  - Lectins are a large group of carbohydrate-binding proteins, having been shown to
      comprise at least 48 protein scaffolds or protein family entries. They occur
      ubiquitously in living organisms-from humans to microorganisms, including viruses
      and while their functions are yet to be fully elucidated, their main underlying
      actions are thought to mediate cell-cell and cell-glycoconjugate interactions,
      which play important roles in an extensive range of biological processes. The
      basic feature of each lectin's function resides in its specific sugar-binding
      properties. In this regard, it is beneficial for researchers to have access to
      fundamental information about the detailed oligosaccharide specificities of
      diverse lectins. In this review, the authors describe a publicly available lectin
      database named "Lectin frontier DataBase (LfDB)", which undertakes the continuous
      publication and updating of comprehensive data for lectin-standard
      oligosaccharide interactions in terms of dissociation constants (Kd's). For Kd
      determination, an advanced system of frontal affinity chromatography (FAC) is
      used, with which quantitative datasets of interactions between immobilized
      lectins and >100 fluorescently labeled standard glycans have been generated. The
      FAC system is unique in its clear principle, simple procedure and high
      sensitivity, with an increasing number (>67) of associated publications that
      attest to its reliability. Thus, LfDB, is expected to play an essential role in
      lectin research, not only in basic but also in applied fields of glycoscience. 

PMID- 25580690
TI  - Antinociceptive effect of hydantoin 3-phenyl-5-(4-ethylphenyl)-imidazolidine-2,4
      dione in mice.
AB  - Imidazolidine derivatives, or hydantoins, are synthetic compounds with different
      therapeutic applications. Many imidazolidine derivatives have
      psychopharmacological properties, such as phenytoin, famous for its
      anticonvulsant efficacy, but also effective in the treatment of neuropathic pain.
      The hydantoin, 3-phenyl-5-(4-ethylphenyl)-imidazolidine-2,4-dione (IM-3),
      synthesized from the amino acid, glycine, was selected for psychopharmacological
      studies in mice on the basis of its chemical and structural similarity with
      phenytoin. The first step of this study was to define the LD50, which determined
      the doses of 50, 100 and 200 mg/kg for subsequent tests. The results obtained
      from the behavioral screening indicated that IM-3 produces decreased ambulation
      and analgesia in mice. Motor coordination and anxiety behavior were not affected
      by treatment with IM-3, as observed in the rotarod and elevated plus-maze tests,
      respectively. Regarding its antinociceptive properties, IM-3 showed efficacy in
      the acetic acid-induced writhing test by increasing the latency of the first
      writhe and reducing the number of writhes, as well as reducing the paw licking
      time in the second phase of the formalin test. The behavior of treated animals
      exposed to the hot plate test, however, did not differ from that of the control
      group. These data suggest that IM-3 has antinociceptive effects in mice, which is
      probably mediated by anti-inflammatory mechanisms. 

PMID- 25580698
TI  - Functional graphene by thiol-ene click chemistry.
AB  - Thiol-ene click reaction was successfully employed for chemical modification of
      graphene oxide (GO) by one-step synthesis. Herein, 2,2-azobis(2
      methylpropionitrile) (AIBN) was used as thermal catalyst and cysteamine
      hydrochloride (HS-(CH2 )2 -NH2 HCl) was used as thiol-containing compound, which
      is incorporated to GO surface upon reaction with the C=C bonds. The hydrochloride
      acts as protecting group for the amine, which is finally eliminated by adding
      sodium hydroxide. The modified GO contains both S- and N-containing groups (NS
      GO). We found that NS-GO sheets form good dispersion in water, ethanol, and
      ethylene glycol. These graphene dispersions can be processed into functionalized
      graphene film. Besides, it was demonstrated that NS-GO was proved to be an
      excellent host matrix for platinum nanoparticles. The developed method paves a
      new way for graphene modification and its functional nanocomposites.

PMID- 25580699
TI  - Thermal conversion of core-shell metal-organic frameworks: a new method for
      selectively functionalized nanoporous hybrid carbon.
AB  - Core-shell structured ZIF-8@ZIF-67 crystals are well-designed and prepared
      through a seed-mediated growth method. After thermal treatment of ZIF-8@ZIF-67
      crystals, we obtain selectively functionalized nanoporous hybrid carbon materials
      consisting of nitrogen-doped carbon (NC) as the cores and highly graphitic carbon
      (GC) as the shells. This is the first example of the integration of NC and GC in
      one particle at the nanometer level. Electrochemical data strongly demonstrate
      that this nanoporous hybrid carbon material integrates the advantageous
      properties of the individual NC and GC, exhibiting a distinguished specific
      capacitance (270 F.g(-1)) calculated from the galvanostatic charge-discharge
      curves at a current density of 2 A.g(-1). Our study not only bridges diverse
      carbon-based materials with infinite metal-organic frameworks but also opens a
      new avenue for artificially designed nanoarchitectures with target
      functionalities. 

PMID- 25580697
TI  - Characterizing Pain Flares From the Perspective of Individuals With Symptomatic
      Knee Osteoarthritis.
AB  - OBJECTIVE: Although pain in knee osteoarthritis (OA) commonly affects activity
      engagement, the daily pain experience has not been fully characterized.
      Specifically, the nature and impact of pain flares is not well understood. This
      study characterized pain flares as defined by participants with knee OA. Pain
      flare occurrence and experience were measured over 7 days. METHODS: This was a
      multiple methods study; qualitative methods were dominant. Data were collected
      during the baseline portion of a randomized controlled trial. Participants met
      criteria for knee OA and had moderate to severe pain. They completed
      questionnaires and a 7-day home monitoring period that captured momentary symptom
      reports simultaneously with physical activity via accelerometry (n = 45).
      Participants also provided individual definitions of pain flare that were used
      throughout the home monitoring period to indicate whether a pain flare occurred.
      RESULTS: Pain flares were described most often by quality (often sharp), followed
      by timing (seconds, minutes) and by antecedents and consequences. When asked if
      their definition of a flare agreed with a supplied definition, 49% of the sample
      reported only "somewhat," "a little," or "not at all." Using individual
      definitions, 78% experienced at least 1 daily pain flare over the home monitoring
      period; 24% had a flare on more than 50% of the monitored days. CONCLUSION: Pain
      flares were common, fleeting, and often experienced in the context of activity
      engagement. Participants' views on what constitutes a pain flare differ from
      commonly accepted definitions. Pain flares are an understudied aspect of the knee
      OA pain experience and require further characterization.

PMID- 25580700
TI  - Double heteroatom functionalization of arenes using benzyne three-component
      coupling.
AB  - Arynes participate in three-component coupling reactions with N, S, P, and Se
      functionalities to yield 1,2-heteroatom-difunctionalized arenes. Using 2
      iodophenyl arylsulfonates as benzyne precursors, we could effectively add
      magnesiated S-, Se-, and N-nucleophilic components to the strained triple bond.
      In the same pot, addition of electrophilic N, S, or P reagents and a copper(I)
      catalyst trapped the intermediate aryl Grignard to produce a variety of 1,2
      difunctionalized arenes. 

PMID- 25580701
TI  - Magnetic engineering of stable rod-shaped stem cell aggregates: circumventing the
      pitfall of self-bending.
AB  - A current challenge for tissue engineering while restoring the function of
      diseased or damaged tissue is to customize the tissue according to the target
      area. Scaffold-free approaches usually yield spheroid shapes with the risk of
      necrosis at the center due to poor nutrient and oxygen diffusion. Here, we used
      magnetic forces developed at the cellular scale by miniaturized magnets to create
      rod-shaped aggregates of stem cells that subsequently matured into a tissue-like
      structure. However, during the maturation process, the tissue-rods spontaneously
      bent and coiled into sphere-like structures, triggered by the increasing cell
      cell adhesion within the initially non-homogeneous tissue. Optimisation of the
      intra-tissular magnetic forces successfully hindered the transition, in order to
      produce stable rod-shaped stem cells aggregates. 

PMID- 25580703
TI  - Photoactivable platforms for nitric oxide delivery with fluorescence imaging.
AB  - The multifaceted role nitric oxide (NO) plays in human physiology and
      pathophysiology has stimulated a massive interest on NO-releasing compounds for
      therapeutic purposes. A main issue associated with use of NO donors is the
      precise spatiotemporal control of the NO release, as its effects are strictly
      site- and dose-dependent. NO photochemical precursors permit surmounting this
      difficulty since triggering with light offers an exquisite control of location
      and timing of NO delivery. On the other hand, the combination of NO photodonors
      with fluorescent components remains an urgent need for image-guided
      phototherapeutic treatments based on the use of NO. Fluorescence techniques
      permit not only an easy tracking of the photoprecursor in a biological
      environment but also the real-time quantification of the NO photoreleased therein
      in a non-invasive fashion. In this Focus Review we seek to provide an overview of
      recent advances in photoactivable platforms developed in our and other
      laboratories which combine the photoregulated release of NO with fluorescent
      functionalities. We shall focus attention on NO photoreleasing systems exhibiting
      1) persistent fluorescence and 2) photoactivable fluorescence signals,
      highlighting their logical design and potential developments for
      phototheranostics. 

PMID- 25580702
TI  - Long-term outcomes of primary systemic light chain (AL) amyloidosis in patients
      treated upfront with bortezomib or lenalidomide and the importance of risk
      adapted strategies.
AB  - Bortezomib and lenalidomide are increasingly used in patients with AL
      amyloidosis, but long term data on their use as primary therapy in AL amyloidosis
      are lacking while early mortality remains significant. Thus, we analyzed the long
      term outcomes of 85 consecutive unselected patients, which received primary
      therapy with bortezomib or lenalidomide and we prospectively evaluated a risk
      adapted strategy based on bortezomib/dexamethasone to reduce early mortality.
      Twenty-six patients received full-dose bortezomib/dexamethasone, 36 patients
      lenalidomide with oral cyclophosphamide and low-dose dexamethasone and 23
      patients received bortezomib/dexamethasone at a dose and schedule adjusted to the
      risk of early death. On intent to treat, 67% of patients achieved a hematologic
      response (24% hemCRs) and 34% an organ response; both were more frequent with
      bortezomib. An early death occurred in 20%: in 36% of those treated with full
      dose bortezomib/dexamethasone, in 22% of lenalidomide-treated patients but only
      in 4.5% of patients treated with risk-adapted bortezomib/dexamethasone. Activity
      of full vs. adjusted dose bortezomib/dexamethasone was similar; twice weekly vs.
      weekly administration of bortezomib also had similar activity. After a median
      follow up of 57 months, median survival is 47 months and is similar for patients
      treated with bortezomib vs. lenalidomide-based regimens. However, risk adjusted
      bortezomib/dexamethasone was associated with improved 1-year survival vs. full
      dose bortezomib/dexamethasone or lenalidomide-based therapy (81% vs. 56% vs. 53%,
      respectively). In conclusion, risk-adapted bortezomib/dexamethasone may reduce
      early mortality and preserve activity while long term follow up indicates that
      remissions obtained with lenalidomide or bortezomib may be durable, even without
      consolidation with alkylators.

PMID- 25580705
TI  - Abdominal Aortic Aneurysms and Risk Factors for Adverse Events.
AB  - An abdominal aortic aneurysm (AAA) is a focal full thickness dilatation of the
      abdominal aorta, greater than 1.5 times its normal diameter. Although some
      patients with AAA experience back or abdominal pain, most remain asymptomatic
      until rupture. The prognosis after AAA rupture is poor. Management strategies for
      patients with asymptomatic AAAs include risk factor reduction, such as smoking
      cessation, optimizing antihypertensive treatment, and treating dyslipidemia, as
      well as surveillance by ultrasound. Currently, aneurysm diameter alone is often
      used to assess risk of rupture. Once the aneurysm diameter reaches 5.5 cm, the
      risk of rupture is considered greater than the risk of intervention and elective
      aneurysm repair is undertaken. There is increasing interest in detecting AAAs
      early, and national screening programs are now in place. Furthermore, there is
      increasing research interest in biomarkers, genetics, and functional imaging to
      improve detection of AAAs at risk of progression and rupture. In this review, we
      discuss risk factors for AAA rupture, which should be considered during the
      management process, to advance current deficiencies in management pathways. 

PMID- 25580706
TI  - Omega-3-carboxylic acid (Epanova) for hypertriglyceridemia.
AB  - Hypertriglyceridemia is a prevalent yet under-addressed condition, often seen in
      association with uncontrolled diabetes mellitus, obesity, and physical
      inactivity. The control of triglyceride (TG) levels is essential to prevent the
      development of coronary artery disease and pancreatitis associated with
      hypertriglyceridemia. Omega-3-carboxylic acid (Epanova) is the third prescription
      omega-3 fatty acid product approved in the United States as an adjunct to diet
      for treating severe hypertriglyceridemia (>= 500 mg/dL). At the approved dosage,
      it reduced baseline serum TG levels by 25-30% in a placebo-controlled study. It
      reduced serum TG levels by an additional 8-15% in patients who were already
      taking statin therapy. It appeared to have a better bioavailability profile
      compared with an equivalent dose of omega-3-acid ethyl ester (Lovaza) in both low
      fat and high-fat diets. However, evidence behind the effects of omega-3
      carboxylic acid on cardiovascular morbidity and mortality, and pancreatitis risk,
      is lacking. Overall, it is well tolerated, but may induce common gastrointestinal
      side effects, such as abdominal pain, nausea, and diarrhea. At this time, omega-3
      carboxylic acid is an alternative adjunct therapy (in addition to diet) for
      hypertriglyceridemia. Its potential clinical benefits over other omega-3
      formulations have yet to be evaluated.

PMID- 25580707
TI  - Current strategies in the evaluation and management of cocaine-induced chest
      pain.
AB  - With each successive year, the number of Emergency Department (ED) visits related
      to illicit drug abuse has progressively increased. Cocaine is the most common
      illegal drug to cause a visit to the ED. Cocaine use results in a variety of
      pathophysiological changes with regards to the cardiovascular system, such as
      constriction of coronary vessels, dysfunction of vascular endothelium, decreased
      aortic elasticity, hemodynamic disruptions, a hypercoagulable state, and direct
      toxicity to myocardial and vascular tissue. The clinical course of patients with
      cocaine-induced chest pain (CCP) is often challenging, and electrocardiographic
      findings can be potentially misleading in terms of diagnosing a myocardial
      infarction. In addition, there is no current satisfactory study regarding
      outcomes of use of various pharmacological drug therapies to manage CCP. At
      present, calcium-channel blockers and nitroglycerin are two pharmacological
      agents that are advocated as first-line drugs for CCP management, although the
      role of labetalol has been controversial and warrants further investigation. We
      performed an extensive search of available literature through a large number of
      scholarly articles previously published and listed on Index Medicus. In this
      review, we put forward a concise summary of the current approach to a patient
      presenting to the ED with CCP and management of the clinical scenario. The
      purpose of this review is to summarize the understanding of cocaine's
      cardiovascular pathophysiology and to examine the current approach for proper
      evaluation and management of CCP. 

PMID- 25580708
TI  - Electrophysiologic analysis of injury to cranial nerve XI during neck dissection.
AB  - BACKGROUND: Despite preservation of the accessory nerve, a considerable number of
      patients report partial nerve damage after modified radical neck dissection
      (MRND) and selective neck dissection. METHODS: Accessory nerve branches for the
      trapezius muscle were stimulated during neck dissection, and the M wave amplitude
      was measured during distinct surgical phases. RESULTS: The accessory nerve was
      mapped in 20 patients. The M wave recordings indicated that major nerve damage
      occurred during dissection at levels IIa and IIb in the most proximal segment of
      the nerve. The M waves evoked from this nerve segment decreased significantly
      during surgery (analysis of variance; p = .001). CONCLUSION: The most significant
      intraoperative injury to the accessory nerve during neck dissection occurs at
      anatomic nerve levels IIa and IIb. (c) 2015 Wiley Periodicals, Inc. Head Neck 38:
      E372-E376, 2016.

PMID- 25580709
TI  - Cumulative summation analysis of learning curve for robot-assisted gastrectomy in
      gastric cancer.
AB  - BACKGROUND: The purpose of this study was to determine the learning curve for
      robot-assisted gastrectomy using the Cumulative Summation (CUSUM) technique.
      METHODS: Two series of consecutive robotic gastrectomy were retrospective
      analyzed. Patient demographics, surgical performance, and short-term outcomes
      were examined and data of operation time were abstracted for the learning curve
      analysis. RESULTS: Similar processes occurred in the two surgeons. Each of their
      learning curves of robotic gastrectomy was best modeled as a third-order
      polynomial, with equation CUSUMOT in minutes equal to 0.0495 case number (3) -
      4.217 case number(2) + 91.206 case number 100.11(R(2) =  .8731) for surgeon A and
      0.0314 case number (3) - 2.4106 case number(2) + 33.682 case number + 315.28(R(2)
      = 0.8816) for surgeon B. They both included three unique phases: an initial
      phase, a well-developed phase, and a mastery phase after the accumulation of
      additional experience. CONCLUSION: The CUSUM method is a useful tool for
      objective evaluation of practical skills for surgeons during the learning phase
      of robotic surgery training. The robotic gastrectomy is found to have a short
      learning curve for experienced laparoscopic surgeons and the popularity of this
      new technology won't reduce because of its difficulty to learn.

PMID- 25580710
TI  - Highly stable and imperceptible electronics utilizing photoactivated
      heterogeneous sol-gel metal-oxide dielectrics and semiconductors.
AB  - Incorporation of Zr into an AlOx matrix generates an intrinsically activated ZAO
      surface enabling the formation of a stable semiconducting IGZO film and good
      interfacial properties. Photochemically annealed metal-oxide devices and circuits
      with the optimized sol-gel ZAO dielectric and IGZO semiconductor layers
      demonstrate the high performance and electrically/mechanically stable operation
      of flexible electronics fabricated via a low-temperature solution process. 

PMID- 25580711
TI  - Rain events decrease boreal peatland net CO2 uptake through reduced light
      availability.
AB  - Boreal peatlands store large amounts of carbon, reflecting their important role
      in the global carbon cycle. The short-term exchange and the long-term storage of
      atmospheric carbon dioxide (CO2 ) in these ecosystems are closely associated with
      the permanently wet surface conditions and are susceptible to drought.
      Especially, the single most important peat forming plant genus, Sphagnum, depends
      heavily on surface wetness for its primary production. Changes in rainfall
      patterns are expected to affect surface wetness, but how this transient rewetting
      affects net ecosystem exchange of CO2 (NEE) remains unknown. This study explores
      how the timing and characteristics of rain events during photosynthetic active
      periods, that is daytime, affect peatland NEE and whether rain event associated
      changes in environmental conditions modify this response (e.g. water table,
      radiation, vapour pressure deficit, temperature). We analysed an 11-year time
      series of half-hourly eddy covariance and meteorological measurements from Degero
      Stormyr, a boreal peatland in northern Sweden. Our results show that daytime rain
      events systematically decreased the sink strength of peatlands for atmospheric
      CO2 . The decrease was best explained by rain associated reduction in light,
      rather than by rain characteristics or drought length. An average daytime growing
      season rain event reduced net ecosystem CO2 uptake by 0.23-0.54 gC m(-2) . On an
      annual basis, this reduction of net CO2 uptake corresponds to 24% of the annual
      net CO2 uptake (NEE) of the study site, equivalent to a 4.4% reduction of gross
      primary production (GPP) during the growing season. We conclude that reduced
      light availability associated with rain events is more important in explaining
      the NEE response to rain events than rain characteristics and changes in water
      availability. This suggests that peatland CO2 uptake is highly sensitive to
      changes in cloud cover formation and to altered rainfall regimes, a process
      hitherto largely ignored. 

PMID- 25580712
TI  - Supraclavicular osteocutaneous free flap: clinical application and surgical
      details for the reconstruction of composite defects of the nose.
AB  - The supraclavicular fasciocutaneous flap is a well-recognized flap in head and
      neck reconstruction. In this report, we describe for the first time a variation
      of this flap, the osteocutaneous supraclavicular (SOC) free flap, which was used
      to reconstruct a composite nasal defect. The defect arose after resection of a
      recurrent squamous cell carcinoma and involved dorsal nasal skin, cartilage, and
      the entire nasal bone. A 6 cm * 4 cm size flap including skin, subcutaneous
      tissue, and a vascularized cortico-periosteal segment of the clavicle was raised
      based on the transverse cervical artery. The flap survived with no complications.
      A satisfactory aesthetic outcome was achieved following two revision procedures.
      We believe that the incorporation of bone to the supraclavicular flap may expand
      its applications in reconstruction of composite nasal and facial defects.

PMID- 25580713
TI  - Development of a liquid chromatography with mass spectrometry method for the
      determination of gelsemine in rat plasma and tissue: Application to a
      pharmacokinetic and tissue distribution study.
AB  - Gelsemine from Gelsemium elegans Benth is a potential anesthetic and analgesic
      agent with no physical dependence and opiate addiction. This study was aimed at
      developing an ultrafast liquid chromatography coupled to tandem mass spectrometry
      method to quantify gelsemine in rat plasma and tissues. Plasma and tissues were
      processed with acetonitrile precipitation, and dendrobine was chosen as the
      internal standard. Sample separation was performed on an ACQUITY HSS T3 column.
      The mobile phase consisted of acetonitrile and 0.1% formic acid aqueous solution.
      Multiple reactions monitoring mode was utilized to detect the compounds of
      interest. The mass spectrometer was operated in the positive ion mode for
      detection. The MS/MS ion transitions monitored were m/z 323.2->70.5 for gelsemine
      and 264.2->108.05 for dendrobine, respectively. The calibration curves were
      linear over the range of 1-500 ng/mL in all biological matrices. The lower limit
      of quantification for rats plasma and tissues was 1.0 ng/mL. The values for inter
      and intraday precision and accuracy were well within the ranges acceptable (<
      15%). It was successfully applied to the pharmacokinetic and tissue distribution
      studies of gelsemine after intravenous doses of 5, 2, and 0.5 mg/kg in rats.
      These data of gelsemine would be useful for clinical application and further
      development. 

PMID- 25580715
TI  - Lethal and behavioral effects of selected novel pesticides on adults of
      Trichogramma pretiosum (Hymenoptera: Trichogrammatidae).
AB  - BACKGROUND: Growing demand for reduced chemical inputs in agricultural systems
      requires more effective integration of biological control with pesticides. The
      egg parasitoid Trichogramma pretiosum Riley is an important natural enemy of
      lepidopteran pests, used in biological control. In an investigation of the
      interaction of T. pretiosum and pesticides, we studied the acute toxicity of 19
      pesticides (insecticides, miticides, fungicides and herbicides) to adult
      parasitoids and the behavioral effects of 11 pesticides on foraging parasitoid
      females, including host antennation, stinging and host feeding. RESULTS: At
      recommended field doses, fipronil, dinotefuran, spinetoram, tolfenpyrad and
      abamectin induced nearly 100% adult mortality within 24 h of exposure to treated
      cotton leaves by comparison with controls. Acetamiprid was also toxic, but
      significantly less so than the former materials. The other pesticides had no
      significant toxic effects. Only glufosinate ammonium exhibited increased toxicity
      among the non-toxic materials when increased two- or fourfold over recommended
      rates. The foraging behavior of parasitoids was affected only by tolfenpyrad
      among the materials tested. CONCLUSION: Most novel pesticides, except for several
      insecticides, exhibited little to no acute toxicity to the parasitoid. Parasitoid
      foraging behavior was only affected by tolfenpyrad, indicating that parasitoids
      could successfully forage on eggs treated with most pesticides evaluated.
      Therefore, many of these pesticides may have good compatibility with
      Trichogramma.

PMID- 25580717
TI  - The Inability of Self-affirmations to Decrease Defensive Bias Toward an Alcohol
      Related Risk Message Among High-Risk College Students.
AB  - OBJECTIVE: To examine the efficacy of a self-affirmation task in deterring
      college alcohol misuse and the importance of preexisting beliefs in predicting
      subsequent behavior change. PARTICIPANTS: Heavy-drinking undergraduates (N = 110)
      participated during the 2011-2012 academic year. METHODS: Participants were
      randomized to complete an affirmation or control task before reading an alcohol
      risk message. Alcohol-related beliefs and behaviors were assessed. Participants
      completed a 2-week online follow-up assessing alcohol-related behaviors. RESULTS:
      Both groups reported increased perceived problem importance, but neither group
      displayed changes in personal risk. Follow-up assessment revealed similar,
      significant declines in peak consumption in both groups, with no significant
      between-group differences. Preexisting beliefs accounted for 5% to 10% of
      variance in drinking outcomes. CONCLUSIONS: An affirmation task does not seem to
      decrease defensive processing or alter high-risk drinking behaviors among college
      students and should not be utilized in lieu of more effective strategies.

PMID- 25580718
TI  - Au nanoparticles-3D graphene hydrogel nanocomposite to boost synergistically in
      situ detection sensitivity toward cell-released nitric oxide.
AB  - In situ detection of nitric oxide (NO) released from living cells has become very
      important in studies of some critical physiological and pathological processes,
      but it is still very challenging due to the low concentration and fast decay of
      NO. A nanocomposite of Au nanoparticles deposited on three-dimensional graphene
      hydrogel (Au NPs-3DGH) was prepared through a facile one-step approach by in situ
      reduction of Au(3+) on 3DGH to build a unique sensing film for a strong
      synergistic effect, in which the highly porous 3DGH offers a large surface area
      while Au NPs uniformly deposited on 3DGH efficiently catalyze the electrochemical
      oxidation of NO for sensitive detection of NO with excellent selectivity, fast
      response, and low detection limit. The sensor was further used to in situ detect
      NO released from living cells under drug stimulation, showing significant
      difference between normal and tumor cells under drug stimulation. 

PMID- 25580719
TI  - Conservation genetics and genomics of amphibians and reptiles.
AB  - Amphibians and reptiles as a group are often secretive, reach their greatest
      diversity often in remote tropical regions, and contain some of the most
      endangered groups of organisms on earth. Particularly in the past decade,
      genetics and genomics have been instrumental in the conservation biology of these
      cryptic vertebrates, enabling work ranging from the identification of populations
      subject to trade and exploitation, to the identification of cryptic lineages
      harboring critical genetic variation, to the analysis of genes controlling key
      life history traits. In this review, we highlight some of the most important ways
      that genetic analyses have brought new insights to the conservation of amphibians
      and reptiles. Although genomics has only recently emerged as part of this
      conservation tool kit, several large-scale data sources, including full genomes,
      expressed sequence tags, and transcriptomes, are providing new opportunities to
      identify key genes, quantify landscape effects, and manage captive breeding
      stocks of at-risk species. 

PMID- 25580721
TI  - Satisfaction with daily occupations amongst asylum seekers in Denmark.
AB  - AIM: The aim of this study was to describe asylum seekers' satisfaction with
      daily occupations and activity level while in a Danish asylum centre, and whether
      this changed over time. Another aim was to describe whether exposure to torture,
      self-rated health measures, and ADL ability were related to their satisfaction
      with daily occupations and activity level. METHODS: A total of 43 asylum seekers
      at baseline and 17 at follow-up were included. The questionnaires Satisfaction
      with Daily Occupations, Major Depression Inventory, WHO-5 Wellbeing, Pain Detect,
      a questionnaire covering torture, and basic social information were used as well
      as Assessment of Motor and Process Skills. RESULTS: The results showed a low
      level of satisfaction with daily occupations at both baseline and follow-up.
      There was no statistically significant change in satisfaction or activity level
      between baseline and the follow-up. Associations between AMPS process skills-
      education, worst pain and activity level--were present at baseline, as was a
      relationship between AMPS process skills and satisfaction. At follow-up,
      associations between WHO-5 and satisfaction and activity level and between MDI
      scores and activity level were found. CONCLUSION: Asylum seekers experience a low
      level of satisfaction with daily occupations, both at arrival and after 10 months
      in an asylum centre. There is a need for further research and development of
      occupation-focused rehabilitation methods for the asylum seeker population.

PMID- 25580722
TI  - Inbreeding and thermal adaptation in Drosophila subobscura.
AB  - Using a well-adapted Drosophila subobscura population (Avala, Serbia), a drastic
      experiment of inbreeding was carried out to assess whether the expected level of
      homozygosity could be reached or if other evolutionary forces affected the
      process. In general, no significant changes of inversion (or arrangement)
      frequencies were detected after 12 brother-sister mating generations.
      Furthermore, no significant differences were obtained between observed and
      expected (under the inbreeding model) karyotypic frequencies. Thus, these results
      seemed to indicate that the main evolutionary factor in the experiment was
      inbreeding. However, in the G12 generation, complete chromosomal fixation was
      reached only in two out of the eight final inbred lines. In these lines, the
      chromosomal compositions were difficult to interpret, but they could be likely a
      consequence of adaptation to particular laboratory conditions (constant 18 
      degrees C, food, light period, etc.). Finally, in a second experiment, the inbred
      lines presented higher fertility at 18  degrees C than at 13  degrees C. Also,
      there was a significant line effect on fertility: inbred line number 6 (A1, J1,
      U1+2; U1+2+6, E8, and O3+4+7) presented the highest values, which maybe the
      result of an adaptation to laboratory conditions. Thus, the results obtained in
      our experiments reflect the adaptive potential of D. subobscura inversions. 

PMID- 25580723
TI  - Acute hearing loss in the only hearing ear of 21 patients.

PMID- 25580720
TI  - Quality control and statistical modeling for environmental epigenetics: a study
      on in utero lead exposure and DNA methylation at birth.
AB  - DNA methylation data assayed using pyrosequencing techniques are increasingly
      being used in human cohort studies to investigate associations between epigenetic
      modifications at candidate genes and exposures to environmental toxicants and to
      examine environmentally-induced epigenetic alterations as a mechanism underlying
      observed toxicant-health outcome associations. For instance, in utero lead (Pb)
      exposure is a neurodevelopmental toxicant of global concern that has also been
      linked to altered growth in human epidemiological cohorts; a potential mechanism
      of this association is through alteration of DNA methylation (e.g., at growth
      related genes). However, because the associations between toxicants and DNA
      methylation might be weak, using appropriate quality control and statistical
      methods is important to increase reliability and power of such studies. Using a
      simulation study, we compared potential approaches to estimate toxicant-DNA
      methylation associations that varied by how methylation data were analyzed
      (repeated measures vs. averaging all CpG sites) and by method to adjust for batch
      effects (batch controls vs. random effects). We demonstrate that correcting for
      batch effects using plate controls yields unbiased associations, and that
      explicitly modeling the CpG site-specific variances and correlations among CpG
      sites increases statistical power. Using the recommended approaches, we examined
      the association between DNA methylation (in LINE-1 and growth related genes IGF2,
      H19 and HSD11B2) and 3 biomarkers of Pb exposure (Pb concentrations in umbilical
      cord blood, maternal tibia, and maternal patella), among mother-infant pairs of
      the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort (n
      = 247). Those with 10 MUg/g higher patella Pb had, on average, 0.61% higher IGF2
      methylation (P = 0.05). Sex-specific trends between Pb and DNA methylation (P <
      0.1) were observed among girls including a 0.23% increase in HSD11B2 methylation
      with 10 MUg/g higher patella Pb. 

PMID- 25580724
TI  - Uganda nursing research agenda: a Delphi study.
AB  - AIM: Use a Delphi Methodology to identify nursing research priorities in Uganda.
      BACKGROUND: Identifying nursing research priorities, empowering researchers, and
      encouraging relevant studies can advance attaining global health goals. The
      Uganda Nurses and Midwives Union identified the need to establish a nursing
      research agenda. Nurse leaders have a priority of increasing the influence of
      nurses in practice and policy. This study was conducted as a preliminary step in
      a long-term strategy to build nurses' capacity in nursing research. METHODS: A
      three-round Delphi study was conducted. The 45 study participants were nurses in
      practice, nurse faculty and members of the Uganda Nurses and Midwives Union. In
      the initial round, the participants wrote their responses during face-to-face
      meetings and the follow-up rounds were completed via email. RESULTS: Maternal and
      child morbidity and HIV/AIDS were identified as research priorities. Nurses also
      identified nursing practice, education and policy as key areas that nursing
      research could impact. LIMITATIONS: Demographic characteristics such as length of
      time in nursing were not collected. Additionally, first round participants
      completed a pencil-paper survey and the follow-up rounds were done by email.
      CONCLUSIONS: Nurse Leaders in Uganda identified areas where research efforts
      could have the most impact and were most relevant to nursing practice.
      IMPLICATIONS FOR NURSING AND HEALTH POLICY: Health policy decisions have
      historically been made without nursing input. Nursing research can provide
      evidence to inform policy and, ultimately, improve population health. The focus
      of nursing research in priority areas can be used to guide nursing contribution
      in policy discussions.

PMID- 25580726
TI  - Outcomes after carotid artery stenting in Medicare beneficiaries, 2005 to 2009.
AB  - IMPORTANCE: Despite increased carotid artery stenting (CAS) dissemination
      following the 2005 National Coverage Determination, to our knowledge,
      periprocedural and long-term outcomes have not been described among Medicare
      beneficiaries. OBJECTIVE: To describe the incidence of outcomes during and after
      the periprocedural period among Medicare beneficiaries undergoing CAS. DESIGN,
      SETTING, AND PARTICIPANTS: Observational study with a mean follow-up time of
      approximately 2 years among 22,516 fee-for-service Medicare beneficiaries at
      least 66 years old undergoing CAS (2005-2009) who were linked to the Centers for
      Medicare & Medicaid Services' CAS database. Database procedure dates were
      required to fall during a Medicare hospitalization for CAS. MAIN OUTCOMES AND
      MEASURES: Periprocedural (30-day) and long-term risks of mortality and stroke or
      transient ischemic attack, as well as periprocedural myocardial infarction.
      Subgroups were based on sociodemographic, clinical, and center-level factors, as
      well as the Stenting and Angioplasty With Protection in Patients at High Risk for
      Endarterectomy (SAPPHIRE) trial or Carotid Revascularization Endarterectomy vs
      Stenting Trial (CREST) enrollment criteria. RESULTS: The mean patient age was
      76.3 years, 60.5% were male, 93.8% were of white race, 91.2% were at high
      surgical risk, 47.4% were symptomatic, and 97.4% had carotid stenosis of at least
      70%. Crude 30-day mortality, stroke or transient ischemic attack, and myocardial
      infarction risks were 1.7% (95% CI, 1.5%-1.8%), 3.3% (95% CI, 3.0%-3.5%), and
      2.5% (95% CI, 2.3%-2.7%), respectively. Mortality during a mean follow-up time of
      2 years was 32.0% (95% CI, 31.0%-33.0%), with rates of 37.3% (95% CI, 35.8%
      38.7%) among symptomatic patients and 27.7% (95% CI, 26.4%-28.9%) among
      asymptomatic patients. Older age, symptomatic carotid stenosis, and nonelective
      hospital admission were associated with increased adjusted hazards of mortality
      and stroke or transient ischemic attack during and after the periprocedural
      period. The presence of a stroke center, government ownership, and a hospital bed
      capacity of 500 or more were associated with increased adjusted hazards of
      periprocedural mortality and stroke or transient ischemic attack. Few patients
      met the SAPPHIRE trial or CREST enrollment criteria primarily because physicians
      did not meet proficiency requirements either due to exceeding periprocedural
      complication trial thresholds or not meeting minimum CAS volume requirements.
      CONCLUSIONS AND RELEVANCE: Competing risks may limit the benefits of CAS in
      certain Medicare beneficiaries, particularly among older and symptomatic patients
      who have higher periprocedural and long-term mortality risks. The
      generalizability of trials like the SAPPHIRE or CREST to the Medicare population
      may be limited, underscoring the need to evaluate real-world effectiveness of
      carotid stenosis treatments.

PMID- 25580727
TI  - Pure ankle dislocation: management with early weight bearing and mobilization.

PMID- 25580729
TI  - Correlates of bushmeat in markets and depletion of wildlife.
AB  - We used data on number of carcasses of wildlife species sold in 79 bushmeat
      markets in a region of Nigeria and Cameroon to assess whether species composition
      of a market could be explained by anthropogenic pressures and environmental
      variables around each market. More than 45 mammal species from 9 orders were
      traded across all markets; mostly ungulates and rodents. For each market, we
      determined median body mass, species diversity (game diversity), and taxa that
      were principal contributors to the total number of carcasses for sale (game
      dominance). Human population density in surrounding areas was significantly and
      negatively related to the percentage ungulates and primates sold in markets and
      significantly and positively related to the proportion of rodents. The proportion
      of carnivores sold was higher in markets with high human population densities.
      Proportion of small-bodied mammals (<1 kg) sold in markets increased as human
      population density increased, but proportion of large-bodied mammals (>10 kg)
      decreased as human population density increased. We calculated an index of game
      depletion (GDI) for each market from the sum of the total number of carcasses
      traded per annum and species, weighted by the intrinsic rate of natural increase
      (rmax ) of each species, divided by individuals traded in a market. The GDI of a
      market increased as the proportion of fast-reproducing species (highest rmax )
      increased and as the representation of species with lowest rmax (slow
      reproducing) decreased. The best explanatory factor for a market's GDI was
      anthropogenic pressure-road density, human settlements with >3000 inhabitants,
      and nonforest vegetation. High and low GDI were significantly differentiated by
      human density and human settlements with >3000 inhabitants. Our results provided
      empirical evidence that human activity is correlated with more depleted bushmeat
      faunas and can be used as a proxy to determine areas in need of conservation
      action.

PMID- 25580730
TI  - Regulation of advanced nurse practice: its existence and regulatory dimensions
      from an international perspective.
AB  - AIM: To explore the regulation of advanced nurse practice internationally and to
      identify differences and commonalities. BACKGROUND: Regulation of advanced
      practice nursing does not occur in many countries. Ireland is currently in the
      minority in regulating advanced practice at a national level. KEY ISSUES: Lack of
      regulation poses difficulties for national governments and for society due to
      uncertainty in advanced practice concept and role. METHODS: A literature review
      of 510 scholarly nursing papers published in CINAHL, PubMed and MEDLINE between
      2002 and 2013 and 30 websites was undertaken. RESULTS: There is a lack of
      consistency in legislative systems internationally. Nursing organisations have
      recognised advanced nurse practice by regulation in some countries and by
      voluntary certification in others. CONCLUSIONS: Research has demonstrated that
      care delivered by advanced nurse practitioners has enhanced patient outcomes yet
      regulation of advanced practice is not undertaken in most countries. IMPLICATIONS
      FOR NURSE MANAGER: Nurse managers need to know that criteria for the regulation
      of advanced practice are in place and reflect the minimum requirements for safe
      practice.

PMID- 25580728
TI  - Electrical impedance myography in the evaluation of the tongue musculature in
      amyotrophic lateral sclerosis.
AB  - INTRODUCTION: Electrical impedance myography (EIM) quantifies muscle health and
      is used as a biomarker of muscle abnormalities in neurogenic and myopathic
      diseases. EIM has yet to be evaluated in the tongue musculature in patients with
      amyotrophic lateral sclerosis (ALS), who often show clinical bulbar signs.
      METHODS: The lingual musculature of 19 subjects with motor neuron disease and 21
      normal participants was assessed using EIM, strength and endurance testing, and
      clinical assessment. RESULTS: Tongue musculature in the ALS group was
      characterized by significantly smaller phase (Ph) and greater resistance (R) when
      compared with the healthy cohort. Ph and tongue endurance were correlated in the
      ALS group. CONCLUSIONS: EIM of tongue musculature could distinguish those with
      ALS from healthy controls. The demonstrated relationship between tongue function
      and Ph supports further testing of EIM of the tongue as a potential biomarker in
      ALS.

PMID- 25580731
TI  - Myeloid heme oxygenase-1 promotes metastatic tumor colonization in mice.
AB  - Heme oxygenase-1 (HO-1) is a heme degradation enzyme with antioxidant and immune
      modulatory functions. HO-1 promotes tumorigenesis by enhancing tumor cell
      proliferation and invasion. Whether HO-1 has an effect on cancer progression
      through stromal compartments is less clear. Here we show that the growth of tumor
      engrafted subcutaneously in syngeneic mice was not affected by host HO-1
      expression. However, lung metastasis arisen from subcutaneous tumor or
      circulating tumor cells was significantly reduced in HO-1(+/-) mice comparing to
      wild type (WT) mice. The reduced lung metastasis was also observed in B6 mice
      bearing HO-1(+/-) bone marrow as comparing to WT chimeras, indicating that HO-1
      expression in hematopoietic cells impacts tumor colonization at the metastatic
      site. Further experiments demonstrated that the numbers of myeloid cells
      recruited to pulmonary premetastatic niches and metastatic loci were
      significantly lower in HO-1(+/-) mice than in WT mice. Likewise, the extents of
      tumor cell extravasation and colonization at the metastatic loci in the early
      phase of metastasis were significantly lower in HO-1(+/-) mice. Mechanistic
      studies revealed that HO-1 impacted chemoattractant-induced myeloid cell
      migration by modulating p38 kinase signaling. Moreover, myeloid HO-1-induced
      expressions of vascular endothelial growth factor and interleukin-10 promoted
      tumor cell transendothelial migration and STAT3 activation in vitro. These data
      support a pathological role of myeloid HO-1 in metastasis and suggest a
      possibility of targeting myeloid HO-1 for cancer treatment.

PMID- 25580725
TI  - Treatment for preventing tuberculosis in children and adolescents: a randomized
      clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and
      isoniazid.
AB  - IMPORTANCE: Three months of a once-weekly combination of rifapentine and
      isoniazid for treatment of latent tuberculosis infection is safe and effective
      for persons 12 years or older. Published data for children are limited.
      OBJECTIVES: To compare treatment safety and assess noninferiority treatment
      effectiveness of combination therapy with rifapentine and isoniazid vs 9 months
      of isoniazid treatment for latent tuberculosis infection in children. DESIGN,
      SETTING, AND PARTICIPANTS: A pediatric cohort nested within a randomized, open
      label clinical trial conducted from June 11, 2001, through December 17, 2010,
      with follow-up through September 5, 2013, in 29 study sites in the United States,
      Canada, Brazil, Hong Kong (China), and Spain. Participants were children (aged 2
      17 years) who were eligible for treatment of latent tuberculosis infection.
      INTERVENTIONS: Twelve once-weekly doses of the combination drugs, given with
      supervision by a health care professional, for 3 months vs 270 daily doses of
      isoniazid, without supervision by a health care professional, for 9 months. MAIN
      OUTCOMES AND MEASURES: We compared rates of treatment discontinuation because of
      adverse events (AEs), toxicity grades 1 to 4, and deaths from any cause. The
      equivalence margin for the comparison of AE-related discontinuation rates was 5%.
      Tuberculosis disease diagnosed within 33 months of enrollment was the main end
      point for testing effectiveness. The noninferiority margin was 0.75%. RESULTS: Of
      1058 children enrolled, 905 were eligible for evaluation of effectiveness. Of 471
      in the combination-therapy group, 415 (88.1%) completed treatment vs 351 of 434
      (80.9%) in the isoniazid-only group (P = .003). The 95% CI for the difference in
      rates of discontinuation attributed to an AE was -2.6 to 0.1, which was within
      the equivalence range. In the safety population, 3 of 539 participants (0.6%) who
      took the combination drugs had a grade 3 AE vs 1 of 493 (0.2%) who received
      isoniazid only. Neither arm had any hepatotoxicity, grade 4 AEs, or treatment
      attributed death. None of the 471 in the combination-therapy group developed
      tuberculosis vs 3 of 434 (cumulative rate, 0.74%) in the isoniazid-only group,
      for a difference of -0.74% and an upper bound of the 95% CI of the difference of
      +0.32%, which met the noninferiority criterion. CONCLUSIONS AND RELEVANCE:
      Treatment with the combination of rifapentine and isoniazid was as effective as
      isoniazid-only treatment for the prevention of tuberculosis in children aged 2 to
      17 years. The combination-therapy group had a higher treatment completion rate
      than did the isoniazid-only group and was safe. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00023452.

PMID- 25580732
TI  - The role of peer support in the development of maternal identity for "NICU Moms".
AB  - OBJECTIVE: To examine first-time neonatal intensive care unit (NICU) mothers'
      perceptions of the initial effect and stress of their birth experiences and
      hospitalizations of their infants and what facilitated or hindered the
      development of their maternal roles within the context of the NICU. DESIGN: A
      qualitative descriptive design. SETTING: A 57-bed, tertiary NICU in Chicago.
      PARTICIPANTS: Twenty-three mothers of very low birth weight (VLBW) infants
      hospitalized in the NICU. METHODS: Participants were a subset of a larger
      longitudinal mixed-method study of psychological distress in 69 mothers of VLBW
      infants. Mothers were interviewed using an adaptation of the Clinical Interview
      for Parents of High-Risk Infants (CLIP) approximately 6 weeks after the births of
      their infants. Data were analyzed using conventional content analysis. RESULTS:
      Mothers characterized the infants' births and hospitalizations as a time of
      overwhelming change culminating in a new perspective on life. Primary themes were
      loss, stress and anxiety, adapting, resilience, peer support, and "I'm a NICU
      Mom." Mothers rated peer support as the most facilitative and supportive aspect
      of developing the maternal role in the NICU. CONCLUSION: Peer support and role
      modeling by NICU-based breastfeeding peer counselors helped the mothers
      throughout every stage of their infants' hospitalizations, from giving them hope,
      to helping them begin to develop maternal identity, to providing anticipatory
      guidance about taking their infants home. Talking points are provided for nurses
      who work in NICUs without dedicated peer support to help mothers establish a
      healthy mother/infant relationship.

PMID- 25580733
TI  - Phylogenetic skew: an index of community diversity.
AB  - The distribution of divergence times between member species of a community
      reflects the pattern of species composition. In this study, we contrast the
      species composition of a community against the meta-community, which we define as
      the species composition of a set of target communities. We regard the collection
      of species that comprise a community as a sample from the set of member species
      of the meta-community, and interpret the pattern of the community species
      composition in terms of the type of species sampled from the meta-community. A
      newly defined effective species sampling proportion explains the amount of the
      difference between the divergence time distributions of the community and that of
      the meta-community, assuming random sampling. We propose a new index of
      phylogenetic skew (PS), as the ratio of the maximum-likelihood estimate of the
      effective species sampling proportion to the observed sampling proportion. A PS
      value of 1 is interpreted as random sampling. If the value is >1, the sampling is
      suspected to be phylogenetically skewed. If it is <1, systematic thinning of
      species is likely. Unlike other indices, the PS does not depend on species
      richness as long as the community has more than a few members of a species.
      Because it is possible to compare partially observed communities, the index may
      be effectively used in exploratory analysis to detect candidate communities with
      unique species compositions from a large number of communities. 

PMID- 25580736
TI  - Impact of inhaled nitric oxide on white matter damage in growth-restricted
      neonatal rats.
AB  - BACKGROUND: Fetal growth restriction is the second leading cause of perinatal
      morbidity and mortality, and neonates with intrauterine growth retardation (IUGR)
      have increased neurocognitive and neuropsychiatric morbidity. These
      neurocognitive impairments are mainly related to injury of the developing brain
      associated with IUGR. Growing evidence from preclinical models of brain injury in
      both adult and neonatal rodents supports the view that nitric oxide can promote
      neuroprotection. METHODS: In a model of IUGR induced by protracted gestational
      hypoxia leading to diffuse white matter injury, we subjected neonatal rats to low
      dose (5 ppm) but long-lasting (7 d) exposure to inhaled NO (iNO). We used a
      combination of techniques, including immunohistochemistry, quantitative PCR, and
      cognitive assessment, to assess neuroprotection. RESULTS: Antenatal hypoxia
      induced IUGR was associated with severe neuroinflammation and delayed
      myelination. iNO exposure during the first postnatal week significantly
      attenuated cell death and microglial activation, enhanced oligodendroglial
      proliferation and finally improved myelination. Remarkably, iNO was associated
      with the specific upregulation of P27kip1, which initiates oligodendrocytic
      differentiation. Finally, iNO counteracted the deleterious effects of hypoxia on
      learning abilities. CONCLUSION: This study provides new evidence that iNO could
      be effective in preventing brain damage and/or enhancing repair of the developing
      brain.

PMID- 25580735
TI  - Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory
      responsiveness and TLR-related gene expression in the fetal human gut.
AB  - BACKGROUND: Bacterial contact in utero modulates fetal and neonatal immune
      responses. Maternal probiotic supplementation reduces the risk of immune-mediated
      disease in the infant. We investigated the immunomodulatory properties of live
      Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal
      models. METHODS: Tumor necrosis factor (TNF)-alpha mRNA expression was measured
      by qPCR in a human fetal intestinal organ culture model exposed to live L.
      rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus
      protein to intestinal epithelial cells (IECs) was assessed in human fetal
      intestinal organ culture and the human fetal intestinal epithelial cell line H4
      by immunohistochemistry and immunofluorescence, respectively. TLR-related gene
      expression in fetal ileal organ culture after exposure to recombinant SpaC was
      assessed by qPCR. RESULTS: Live L. rhamnosus GG significantly attenuates pathogen
      induced TNF-alpha mRNA expression in the human fetal gut. Recombinant SpaC
      protein was found to adhere to the fetal gut and to modulate varying levels of
      TLR-related gene expression. CONCLUSION: The human fetal gut is responsive to
      luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal
      inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin
      SpaC binds to immature human IECs and directly modulates IEC innate immune gene
      expression.

PMID- 25580734
TI  - Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated
      macrophages and promotes malignant growth.
AB  - Tumour-associated macrophages (TAMs) are enriched in glioblastoma multiformes
      (GBMs) that contain glioma stem cells (GSCs) at the apex of their cellular
      hierarchy. The correlation between TAM density and glioma grade suggests a
      supportive role for TAMs in tumour progression. Here we interrogated the
      molecular link between GSCs and TAM recruitment in GBMs and demonstrated that
      GSCs secrete periostin (POSTN) to recruit TAMs. TAM density correlates with POSTN
      levels in human GBMs. Silencing POSTN in GSCs markedly reduced TAM density,
      inhibited tumour growth, and increased survival of mice bearing GSC-derived
      xenografts. We found that TAMs in GBMs are not brain-resident microglia, but
      mainly monocyte-derived macrophages from peripheral blood. Disrupting POSTN
      specifically attenuated the tumour-supportive M2 type of TAMs in xenografts.
      POSTN recruits TAMs through the integrin alphavbeta3 as blocking this signalling
      by an RGD peptide inhibited TAM recruitment. Our findings highlight the
      possibility of improving GBM treatment by targeting POSTN-mediated TAM
      recruitment.

PMID- 25580738
TI  - Association of primary immune thrombocytopenia and common allergic diseases among
      children.
AB  - BACKGROUND: Growing evidence has revealed a link between autoimmune and allergic
      diseases. However, few studies have assessed the relationship between allergic
      diseases and primary immune thrombocytopenia (ITP), an autoimmune disease
      frequently occurring in children. This population-based case-control study
      investigated the association between common allergic diseases and the subsequent
      risk of developing ITP during childhood. METHODS: This study investigated 1,203
      children younger than 18 y of age who were diagnosed with ITP between 1998 and
      2008, as well as 4,812 frequency-matched controls. The odds ratios of the
      association between ITP and preexisting allergic diseases were calculated.
      RESULTS: Children with every type of allergic disease examined in this study
      (except asthma) exhibited an increased risk of developing ITP; the lowest
      adjusted odds ratio (aOR) was 1.39 for allergic conjunctivitis (95% confidence
      interval (CI) = 1.09-1.79), whereas the greatest aOR was 1.84 for allergic
      rhinitis (95% CI = 1.49-2.27). The aORs increased with the number of concurrent
      allergic diseases to 2.89 (95% CI = 1.98-4.22) for children with at least three
      allergic diseases. CONCLUSION: Children with atopic diathesis have a greater risk
      of subsequently developing ITP. The fundamental determinants of this relationship
      warrant further study.

PMID- 25580737
TI  - Altered pulmonary artery endothelial-smooth muscle cell interactions in
      experimental congenital diaphragmatic hernia.
AB  - BACKGROUND: Pulmonary hypertension (PH) secondary to vascular remodeling
      contributes to poor outcomes in congenital diaphragmatic hernia (CDH), however
      mechanisms responsible are unknown. We hypothesized that pulmonary artery
      endothelial cell (PAEC) dysfunction contributes to smooth muscle cell (SMC)
      hyperplasia in experimental CDH. METHODS: PAEC and SMC were isolated from fetal
      sheep with experimental CDH and controls. SMC growth was assessed alone and with
      SOD plus catalase and during coculture with control or CDH PAEC with and without
      ET-1 siRNA transfection. ET-1 protein was measured in PAEC and SMC lysates and
      supernatant. ROS production was measured in normal and CDH PAECs with and without
      ET-1 siRNA. PAEC growth and tube formation were measured with SOD plus catalase.
      RESULTS: CDH SMC growth was decreased and increased with coculture with CDH PAEC
      more than control PAEC. Treatment of CDH PAEC with SOD plus catalase or ET-1
      siRNA prevented the increase in SMC growth seen with coculture. ET-1 protein was
      increased in CDH PAEC and SMC. ROS production was increased in CDH PAEC and
      decreased with ET-1 SiRNA. SOD plus catalase restored CDH PAEC growth and tube
      formation. CONCLUSION: PAEC dysfunction in experimental CDH increases SMC
      proliferation via ET-1 induced ROS production by PAEC.

PMID- 25580739
TI  - Thymic and bone marrow output in individuals with 22q11.2 deletion syndrome.
AB  - BACKGROUND: The 22q11.2 deletion syndrome (22q11.2DS) is a congenital multisystem
      anomaly characterized by typical facial features, palatal anomalies, congenital
      heart defects, hypocalcemia, immunodeficiency, and cognitive and neuropsychiatric
      symptoms. The aim of our study was to investigate T- and B-lymphocyte
      characteristics associated with 22q11.2DS. METHODS: Seventy-five individuals with
      22q11.2DS were tested for T and B lymphocytes by examination of T-cell receptor
      rearrangement excision circles (TRECs) and B-cell kappa-deleting recombination
      excision circles (KRECs), respectively. RESULTS: The 22q11.2DS individuals
      displayed low levels of TRECs, while exhibiting normal levels of KRECs. There was
      a significant positive correlation between TREC and KREC in the 22q11.2DS group,
      but not in controls. Both TREC and KREC levels showed a significant decrease with
      age and only TREC was low in 22q11.2DS individuals with recurrent infections. No
      difference in TREC levels was found between 22q11.2DS individuals who underwent
      heart surgery (with or without thymectomy) and those who did not. CONCLUSION: T
      cell immunodeficiency in 22q11.2DS includes low TREC levels, which may contribute
      to recurrent infections in individuals with this syndrome. A correlation between
      T- and B-cell abnormalities in 22q11.2DS was identified. The B-cell abnormalities
      could account for part of the immunological deficiency seen in 22q11.2DS.

PMID- 25580740
TI  - Relationship between T-cell HLA-DR expression and intravenous immunoglobulin
      treatment response in Kawasaki disease.
AB  - BACKGROUND: Kawasaki disease (KD) is an acute febrile illness associated with the
      development of vasculitis. Administration of intravenous immunoglobulin (IVIG) is
      the standard treatment for KD. However, IVIG treatment is not effective in
      approximately 15% of children with KD. Some reports have presented evidence of
      immunological responses in IVIG-resistant KD patients. We assessed the
      possibility that T-cell activation is a contributing mechanism underlying this
      phenomenon. METHODS: We analyzed human leukocyte antigen-DR (HLA-DR) expression
      on peripheral blood CD4+ and CD8+ T cells in 82 children with KD who were
      admitted to the hospital between October 2007 and February 2012. We compared the
      percentages of HLA-DR+ T cells among the CD4+ T-cell and CD8+ T-cell populations
      for the IVIG-effective and IVIG-resistant groups. RESULTS: Among the 82 subjects,
      51 had IVIG-effective KD and 31 children had IVIG-resistant KD. The percentages
      of HLA-DR+ T cells among the CD4+ T-cell and CD8+ T-cell populations in the IVIG
      effective group were significantly lower than those in the IVIG-resistant group.
      CONCLUSION: Our results suggest that increased T-cell HLA-DR expression is
      associated with IVIG resistance in KD patients, indicating that HLA-DR expression
      would be a useful tool for predicting IVIG responsiveness during KD pathogenesis.

PMID- 25580741
TI  - Bioactive peptides released from in vitro digestion of human milk with or without
      pasteurization.
AB  - BACKGROUND: Pasteurized donor human milk (HM) serves as the best alternative for
      breast-feeding when availability of mother's milk is limited. Pasteurization is
      also applied to mother's own milk for very low birth weight infants, who are
      vulnerable to microbial infection. Whether pasteurization affects protein
      digestibility and therefore modulates the profile of bioactive peptides released
      from HM proteins by gastrointestinal digestion, has not been examined to date.
      METHODS: HM with and without pasteurization (62.5  degrees C for 30 min) were
      subjected to in vitro gastrointestinal digestion, followed by peptidomic analysis
      to compare the formation of bioactive peptides. RESULTS: Some of the bioactive
      peptides, such as caseinophosphopeptide homologues, a possible opioid peptide (or
      propeptide), and an antibacterial peptide, were present in undigested HM and
      showed resistance to in vitro digestion, suggesting that these peptides are
      likely to exert their bioactivities in the gastrointestinal lumen, or be stably
      transported to target organs. In vitro digestion of HM released a large variety
      of bioactive peptides such as angiotensin I-converting enzyme-inhibitory,
      antioxidative, and immunomodulatory peptides. Bioactive peptides were released
      largely in the same manner with and without pasteurization. CONCLUSION: Provision
      of pasteurized HM may be as beneficial as breast-feeding in terms of milk protein
      derived bioactive peptides.

PMID- 25580743
TI  - Community-based prevalence and clinical characteristics of febrile seizures in
      Tanzania.
AB  - BACKGROUND: The prevalence of febrile seizures (FSs) and epilepsy are often
      reported to be higher in sub-Saharan Africa. Furthermore, several studies
      describe complex features of FSs as risk factors for the development of
      subsequent epilepsy. METHODS: During the period from 2002 to 2004 door-to-door
      studies with supplementary data collection were conducted in three different
      areas of Tanzania, examining the prevalence of FSs in 7,790 children between the
      age of 2 mo and 7 y at the time of the interview. The information on the presence
      of FSs of 14,583 children, who at the time of the interview were younger than 15
      y, was collected in order to describe reported seizures, if any. RESULTS:
      Overall, 160 children between 2 mo and 7 y with a prevalence rate of 20.5/1,000
      (95% confidence interval: 17.5-23.9/1,000) met the criteria for FSs. The average
      age at onset was 2.2 (SD: 1.8) y and ~42% had complex FSs. Respiratory tract
      infections and malaria were the most frequent concomitant diseases. CONCLUSION:
      Our findings do not confirm the assumption of an increased prevalence of FSs in
      sub-Saharan Africa. However, the elevated number of complex FSs emphasizes the
      necessity of more reliable studies about FSs and its consequences.

PMID- 25580742
TI  - Integrin-linked kinase mediates CTGF-induced epithelial to mesenchymal transition
      in alveolar type II epithelial cells.
AB  - BACKGROUND: Overexpression of connective tissue growth factor (CTGF) in alveolar
      type II epithelial (AT II) cells disrupts alveolar structure, causes interstitial
      fibrosis, and upregulates integrin-linked kinase (ILK). Whether CTGF-ILK
      signaling induces epithelial to mesenchymal transition (EMT) in AT II cells is
      unknown. METHODS: Transgenic mice with targeted overexpression of CTGF in AT II
      cells were generated utilizing the surfactant protein C (SP-C) gene promoter and
      doxycycline-inducible system. AT II cells were isolated from 4-wk-old CTGF
      overexpressing (CTGF+) mice and control littermates, and cultured on Matrigel.
      Cells were transfected with ILK siRNA, and cell morphology and expression of cell
      differentiation markers were analyzed. RESULTS: The AT II cells from the control
      lungs grew in clusters and formed alveolar-like cysts and expressed SP-C. In
      contrast, the cells from CTGF+ lungs were spread and failed to form alveolar-like
      cysts. These cells expressed higher levels of CTGF, alpha smooth muscle actin
      (alpha-SMA), fibronectin and vimentin, the mesenchymal markers, suggesting EMT
      like changes. Transfection with ILK siRNA not only dramatically attenuated ILK
      expression, but also decreased alpha-SMA expression as well as reversed cell
      morphological changes in CTGF+ AT II cells. CONCLUSION: Overexpression of CTGF
      induces EMT in mouse primary AT II cells and this is mediated by ILK.

PMID- 25580744
TI  - Nickel acts as an adjuvant during cobalt sensitization.
AB  - Metal allergy is the most frequent form of contact allergy with nickel and cobalt
      being the main culprits. Typically, exposure comes from metal-alloys where nickel
      and cobalt co-exist. Importantly, very little is known about how co-exposure to
      nickel and cobalt affects the immune system. We investigated these effects by
      using a recently developed mouse model. Mice were epicutaneously sensitized with
      i) nickel alone, ii) nickel in the presence of cobalt, iii) cobalt alone, or iv)
      cobalt in the presence of nickel, and then followed by challenge with either
      nickel or cobalt alone. We found that sensitization with nickel alone induced
      more local inflammation than cobalt alone as measured by increased ear-swelling.
      Furthermore, the presence of nickel during sensitization to cobalt led to a
      stronger challenge response to cobalt as seen by increased ear-swelling and
      increased B and T cell responses in the draining lymph nodes compared to mice
      sensitized with cobalt alone. In contrast, the presence of cobalt during nickel
      sensitization only induced an increased CD8(+) T cell proliferation during
      challenge to nickel. Thus, the presence of nickel during cobalt sensitization
      potentiated the challenge response against cobalt more than the presence of
      cobalt during sensitization to nickel affected the challenge response against
      nickel. Taken together, our study demonstrates that sensitization with a mixture
      of nickel and cobalt leads to an increased immune response to both nickel and
      cobalt, especially to cobalt, and furthermore that the adjuvant effect appears to
      correlate with the inflammatory properties of the allergen.

PMID- 25580745
TI  - Effect of maternal age at childbirth on insulin resistance: the 2010 Korean
      National Health and Nutrition Examination Survey.
AB  - OBJECTIVE: This study aimed to assess insulin resistance according to maternal
      age at childbirth. PATIENTS AND METHODS: The data used in this study were
      obtained from the 2010 Korean National Health and Nutrition Examination Survey.
      This study included a total of 2233 nondiabetic female subjects >=30 years of age
      that were subdivided into groups according to their obesity and abdominal obesity
      (AOB) statuses. The homoeostasis model assessment of insulin resistance (HOMA-IR)
      was used to quantify the insulin resistance according to age at first childbirth
      and last childbirth. RESULTS: Age at first childbirth showed a negative
      relationship with HOMA-IR in both the nonobese and non-AOB groups, while age at
      last childbirth showed a positive relationship with HOMA-IR in both the nonobese
      and non-AOB groups. A multivariate logistic regression analysis revealed that
      ages at first and last childbirth were significantly associated with the highest
      HOMA-IR quartile. The odds ratio was 0.9 (95% confidence interval: 0.82-0.98) for
      age at first childbirth, and 1.07 (95% confidence interval: 1.01-1.14) for age at
      last childbirth in the nonobese and non-AOB groups. CONCLUSION: In conclusion,
      this study suggests that insulin resistance is increased in females who
      experienced their first childbirth at a younger age or their last childbirth at a
      later age, particularly in nonobese individuals. Because these data suggest that
      childbearing age could be an independent risk factor for diabetes, a high-quality
      prospective study assessing the relationship between childbearing age and insulin
      resistance should be performed.

PMID- 25580747
TI  - The Jack Pribaz Foundation and KCNQ2.org.

PMID- 25580748
TI  - Cross-cultural barriers to health care.
AB  - Culturally sensitive health care represents a real ethical and practical need in
      a Western healthcare system increasingly serving a multiethnic society. This
      review focuses on cross-cultural barriers to health care and incongruent aspects
      from a cultural perspective in the provision of health care. To overcome
      difficulties in culturally dissimilar interactions and eventually remove cross
      cultural barriers to health care, a culturally sensitive physician considers his
      or her own identity, values, and beliefs; recognizes the similarities and
      differences among cultures; understands what those similarities and differences
      mean; and is able to bridge the differences to accomplish clear and effective
      communication. 

PMID- 25580746
TI  - Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are
      dysfunctional despite maintaining viability.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease
      for which a greater understanding of early disease mechanisms is needed to reveal
      novel therapeutic targets. We report the use of human induced pluripotent stem
      cell (iPSC)-derived motoneurons (MNs) to study the pathophysiology of ALS. We
      demonstrate that MNs derived from iPSCs obtained from healthy individuals or
      patients harbouring TARDBP or C9ORF72 ALS-causing mutations are able to develop
      appropriate physiological properties. However, patient iPSC-derived MNs,
      independent of genotype, display an initial hyperexcitability followed by
      progressive loss of action potential output and synaptic activity. This loss of
      functional output reflects a progressive decrease in voltage-activated Na(+) and
      K(+) currents, which occurs in the absence of overt changes in cell viability.
      These data implicate early dysfunction or loss of ion channels as a convergent
      point that may contribute to the initiation of downstream degenerative pathways
      that ultimately lead to MN loss in ALS. 

PMID- 25580749
TI  - Commentary on "cross-cultural barriers to health care".

PMID- 25580751
TI  - Commentary on "pediatric dyslipidemia: recommendations for clinical management".

PMID- 25580750
TI  - Pediatric dyslipidemia: recommendations for clinical management.
AB  - During the last 50 years, it has become evident that atherosclerosis originates
      in childhood. Although cardiovascular disease (CVD) events are rare in children,
      autopsy data and imaging studies have documented subclinical disease in
      association with measurable risk factors during childhood. When present at a
      young age, risk factors track into adulthood and have been associated with a
      moderate to high risk of future CVD. As such, the ability to identify this
      vulnerable population creates the opportunity to prevent the development of risk
      factors and future CVD events with effective management of genetic and acquired
      risk factors. In 2011, the National Heart, Lung, and Blood Institute Expert Panel
      published comprehensive guidelines summarizing the current evidence and providing
      developmentally appropriate recommendations for screening, treatment, and follow
      up of children and adults younger than 21 years at risk for premature CVDs such
      as myocardial infarction and stroke. In addition to screening individuals with a
      family history of hypercholesterolemia and/or premature CVD, the Expert Panel
      recommended universal screening of all children between 9 and 11 years of age and
      then again between 17 and 21 years of age. Although the recommendation for
      universal screening, regardless of general health or the presence/absence of risk
      factors of CVD, is not without controversy, this review serves to create
      awareness among healthcare providers, elected officials, and the lay public about
      the burden of CVD, the opportunity for prevention, and the benefits of early and
      effective therapeutic intervention with lifestyle changes and lipid-lowering
      medications. 

PMID- 25580752
TI  - Practice patterns of general gynecologic surgeons versus gynecologic
      subspecialists for concomitant apical suspension during vaginal hysterectomy for
      uterovaginal prolapse.
AB  - OBJECTIVES: We hypothesized that subspecialists perform more concomitant apical
      suspensions during transvaginal hysterectomy for uterovaginal prolapse as
      compared with general gynecologists. METHODS: Retrospective analysis of the
      MedStar Health EXPLORYS database for women undergoing transvaginal hysterectomy
      for prolapse. Appropriate International Classification of Diseases-9 codes for
      uterine prolapse and incomplete and complete uterovaginal prolapse along with
      Current Procedural Terminology codes were used to determine frequency of
      transvaginal hysterectomy alone, transvaginal hysterectomy plus nonapical repair,
      and transvaginal hysterectomy plus concomitant apical suspension. RESULTS: A
      total of 946 patients underwent vaginal hysterectomy for prolapse, with 5.5 years
      follow-up. Thirty-five percent (n = 334) underwent transvaginal hysterectomy
      alone, 20% (n = 184) underwent transvaginal hysterectomy plus nonapical repair,
      and 45% (n = 428) underwent transvaginal hysterectomy plus apical suspension.
      Seventy-two percent of patients operated on by general gynecologists compared
      with 4% of patients operated on by urogynecologists had a transvaginal
      hysterectomy alone. Only 10% of patients operated on by general gynecologic
      surgeons compared with 78% operated on by urogynecologists received a concomitant
      apical suspension for prolapse (P < 0.0001). Forty-four patients (4.7%) required
      repeat surgery for recurrent prolapse. Because of the small number of repeat
      surgeries, preoperative degree of prolapse and type of index procedure did not
      significantly affect the need for repeat surgery. CONCLUSIONS: The majority of
      prolapse procedures involving hysterectomies performed by general gynecologists
      do not include apical suspension, whereas urogynecologic subspecialists
      consistently perform apical suspension.

PMID- 25580753
TI  - Implementation of a CIWA-Ar alcohol withdrawal protocol in a veterans hospital.
AB  - OBJECTIVES: The South Texas Veterans Health Care System (STVHCS) implemented a
      Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)
      based alcohol-withdrawal protocol in June 2013. The aim of this study was to
      determine the efficacy and safety of the new protocol. The primary objective was
      the evaluation of whether implementation of the CIWA-Ar alcohol-withdrawal
      protocol decreased the average length of hospital stay for patients admitted with
      alcohol withdrawal syndrome (AWS) as compared with treatment before the
      introduction of the protocol. Secondary endpoints evaluated benzodiazepine (BZD)
      prescribing practices, use of adjunctive medications for AWS, and safety
      outcomes. METHODS: We reviewed 748 admissions with documented AWS or alcohol
      related diagnoses during the study periods of July 2012 to December 2012
      (preprotocol) and July 2013 to December 2013 (postprotocol). Patients in the
      preprotocol group needed to have a scheduled dose of a BZD in the electronic
      medical record, and those assigned to the postprotocol group needed to have at
      least one documented CIWA-Ar note in their electronic medical record. Exclusion
      criteria included prior conditions that interfered with accurate treatment of
      alcohol withdrawal. RESULTS: There were no statistical differences in baseline
      characteristics between groups. No difference was found in the primary endpoint
      of length of stay when comparing hospitalizations pre- and postprotocol
      implementation (3.84 +/- 2.31 days vs 3.82 +/- 2.7 days; P = 0.667). There was no
      statistical significance in total cumulative dose of BZD, daily dose of BZD, or
      duration of BZD use when compared pre- and postprotocol. No safety events
      requiring further intervention occurred. CONCLUSIONS: Implementation of a CIWA-Ar
      protocol at our institution did not result in a decreased duration of hospital
      stay; however, a decline in prescribing fixed-schedule BZDs was documented.

PMID- 25580755
TI  - Commentary on "Relation between BMI and Diabetes Mellitus and its complications
      among US older adults".

PMID- 25580754
TI  - Relation between BMI and diabetes mellitus and its complications among US older
      adults.
AB  - OBJECTIVES: This study examined relations between elevated body mass index (BMI)
      and time to diagnosis with type 2 diabetes mellitus and its complications among
      older adults in the United States. METHODS: Data came from the Medicare Current
      Beneficiary Survey, 1991-2010. A Cox proportional hazard model was used to assess
      relations between excess BMI at the first Medicare Current Beneficiary Survey
      interview and time to diabetes mellitus diagnosis, complications, and insulin
      dependence among Medicare beneficiaries, older than 65 years of age with no prior
      diabetes mellitus diagnosis, and who were not enrolled in Medicare Advantage (N =
      14,657). RESULTS: Among individuals diagnosed as having diabetes mellitus,
      elevated BMIs were associated with a progressively higher risk of complications
      from diabetes mellitus. For women with a BMI >=40, the risk of insulin dependence
      (hazard ratio [HR] 3.57; 95% confidence interval [CI] 2.36-5.39) was twice that
      for women with 25 <= BMI < 27.5 (HR 1.77; 95% CI 1.33-2.33). A similar pattern
      was observed in risk of cardiovascular (25 <= BMI < 27.5: HR 1.34; 95% CI 1.15
      1.54; BMI >=40: HR 2.45; 95% CI 1.92-3.11), cerebrovascular (25 <= BMI < 27.5: HR
      1.30; 95% CI 1.06-1.57; BMI >=40: HR 2.00; 95% CI 1.42-2.81), renal (25 <= BMI <
      27.5: HR 1.31; 95% CI 1.04-1.63; BMI >=40: HR 2.23; 95% CI 1.54-3.22), and lower
      extremity complications (25 <= BMI < 27.5: HR 1.41; 95% CI 1.22-1.61; BMI >=40:
      HR 2.95; 95% CI 2.35-3.69). CONCLUSIONS: Any increase in BMI above normal weight
      levels is associated with an increased risk of being diagnosed as having
      complications of diabetes mellitus. For men, the increased risk of these
      complications occurred at higher BMI levels than in women. Ocular complications
      occurred at higher BMI levels than other complication types in both men and
      women.

PMID- 25580756
TI  - Upper gastrointestinal symptoms in medical professionals: a higher burden?
AB  - OBJECTIVES: Gastroesophageal reflux disease (GERD) and dyspepsia cause
      significant healthcare resource utilization and greatly affect quality of life;
      therefore, a tendency exists to self-treat in lieu of formal diagnosis. Although
      their prevalence is established in the general population, their prevalence in
      physicians remains unknown. Our aim was to estimate the prevalence of GERD and
      dyspepsia symptoms in a sample of medical professionals by level of training.
      METHODS: An anonymous, computer-based questionnaire was distributed to medical
      students, residents/fellows, and attending physicians at our institution. The
      survey included symptom-based questions for GERD (Reflux Disease Questionnaire);
      quality-of-life questionnaire for dyspepsia (Nepean Dyspepsia Index [NDI]), and
      the Gastroparesis Cardinal Symptom Index (GCSI). We calculated scores based on
      the validated system from each questionnaire and used appropriate statistical
      analysis to evaluate associations between symptomatology and training level
      (medical students, residents/fellows, and attending physicians). RESULTS:
      Overall, there were 327 respondents (155 medical students, 127 residents/fellows,
      45 attending physicians), of whom 52% were women, 56% were white non-Hispanic,
      19% were Hispanic, and 74% were born in the United States/Canada. A total of 21%
      reported previously diagnosed GERD/dyspepsia, and 42% reported previously or
      currently using a medication for GERD/dyspepsia, with significantly higher use of
      proton pump inhibitors in attending physicians than in medical students and
      residents/fellows (P < 0.01). Higher median total scores for the NDI (P = 0.01)
      and GCSI (P < 0.01) in medical students exist compared with residents/fellows and
      attending physicians, with no significant differences for the Reflux Disease
      Questionnaire among groups. CONCLUSIONS: Although the prevalence of diagnosed
      GERD/dyspepsia in our sample was comparable to the general population, medication
      use was higher. Self-treatment with prescription medications increased with
      training. Median NDI and GCSI scores were inversely related to training level,
      which may reflect self-treatment in medical professionals with advanced training.
      Further study of GERD/dyspepsia in medical professionals is warranted.

PMID- 25580757
TI  - Protective effect of pulmonary hypertension against right-sided tamponade in
      pericardial effusion.
AB  - Patients with pericardial effusion are susceptible to cardiac tamponade. A
      compressing circumferential pericardial effusion typically results in an
      equalization of intracardiac and pericardial pressure during diastole and a
      progressive collapse of the right atrium and ventricle. Pulmonary hypertension
      that increases the afterload of the right ventricle may result in elevated
      pressures initially in the right ventricle and subsequently in the right atrium.
      This may lead to right ventricular hypertrophy and a pathologic structural and
      functional remodeling of both right heart chambers. Conversely, elevated
      pressures within the right heart chambers caused by longstanding pulmonary
      hypertension may resist and protect against tamponade of these chambers in the
      setting of a coexisting pericardial effusion. In such cases, a sudden reduction
      in pulmonary arterial pressures may result in tamponade of the right heart
      chambers. 

PMID- 25580758
TI  - Commentary on "protective effect of pulmonary hypertension against right-sided
      tamponade in pericardial effusion".

PMID- 25580759
TI  - Use of pulmonary arterial hypertension-specific therapy in non-WHO group I
      pulmonary hypertension.
AB  - OBJECTIVES: The development of pulmonary hypertension (PH) in non-World Health
      Organization group I PH adversely affects exercise capacity. It is unclear
      whether pulmonary artery hypertension (PAH)-specific drugs improve pulmonary
      hemodynamics and exercise capacity in such patients. METHODS: We performed a
      retrospective chart review of consecutive patients with non-World Health
      Organization group I PH treated with PAH-specific therapy. RESULTS: We identified
      24 patients. The mean (standard deviation) age was 48 (14.8) years. Seventeen
      (71%) patients were women. The 6-minute walk distance improved significantly for
      the whole group in an initial follow-up period of 4.6 (2.3) months; however, the
      improvement was seen only in patients with obstructive sleep apnea (OSA) or
      severe PH and it was not sustained during a longer follow-up period of 11.5 (4.1)
      months, except in patients with OSA. PH was treated with a variety of PAH
      specific drugs, including combination therapy in five patients. CONCLUSIONS: The
      use of PAH-specific therapy in selected patients with PH secondary to lung
      diseases, OSA, or sarcoidosis may result in significant improvement in 6-minute
      walk distance, particularly in patients with OSA or severe PH.

PMID- 25580760
TI  - Modern management of thoracic empyema.
AB  - OBJECTIVES: Historically, surgical management of empyema was performed
      predominantly via open thoracotomy; however, during the past decade the use of
      video-assisted thoracoscopic surgery (VATS) as an alternative has increased. This
      study retrospectively compared the outcomes and management of patients with
      empyema at the University of Kentucky Medical Center who had undergone VATS
      versus those receiving open thoracotomy to determine whether VATS decortication
      provided comparable results. METHODS: Adult patients who had undergone open
      thoracotomy or VATS decortication for empyema between 2005 and 2009 at the
      University of Kentucky were identified by querying the hospital's cardiothoracic
      surgery database. Patients were sorted by procedure on an intent-to-treat basis.
      Comorbid conditions, preoperative course, operative outcomes, and postoperative
      outcomes were compared. Quantitative data were analyzed with either an unpaired t
      test or the Mann-Whitney U test. Qualitative data were analyzed using the Fisher
      exact test. RESULTS: Fifty-three patients were identified, 18 of whom underwent
      VATS and 35 underwent open thoracotomy. Eight of the 18 VATS procedures (44.4%)
      were converted to open thoracotomy. Patients undergoing VATS had a significantly
      shorter median length of stay (11 vs 18 days, respectively; P = 0.044), chest
      tube duration (6 vs 12 days, respectively; P < 0.001), operative blood loss (55.6
      vs 344 mL, respectively; P = 0.003), and fewer postoperative respiratory failures
      (0% vs 22.9%, respectively; P = 0.0451). The two groups did not differ
      significantly in overall morbidity, reoperation, mortality, or preoperative
      comorbidities. CONCLUSIONS: In adults, VATS offers results comparable to those of
      open thoracotomy, and lengths of stay, chest tube durations, and postoperative
      outcomes are superior. Although the conversion rate of VATS to open thoracotomy
      at our institution was high (38.1%) compared with studies at other institutions,
      the data still indicate that VATS is both a safe and reliable alternative to open
      thoracotomy.

PMID- 25580761
TI  - No to greed.

PMID- 25580762
TI  - Commentary on "no to greed".

PMID- 25580763
TI  - Mnemonics for assessing and addressing spiritual care needs of the caregiver.

PMID- 25580764
TI  - Editor's Response.

PMID- 25580765
TI  - Use of standard donors in fecal microbiotal transplants.

PMID- 25580767
TI  - The uncertainty of truth.

PMID- 25580768
TI  - Characterization of bacteria degrading 3-hydroxy palmitic acid methyl ester (3OH
      PAME), a quorum sensing molecule of Ralstonia solanacearum.
AB  - Bacterial wilt pathogen Ralstonia solanacearum causes severe crop loss of
      eggplant, which is of economic importance in India. 3-hydroxy palmitic acid
      methyl ester (3OH-PAME) is the main quorum sensing molecule governing the
      expression of virulence factors in R. solanacearum. Ability of 164 bacterial
      isolates from the xylem of eggplant (Solanum melongena L.), chilli pepper
      (Capsicum annuum L.) and wild eggplant (Solanum torvum Sw.) to degrade 3OH-PAME
      was tested by disc diffusion assay. Enzymatic degradation of 3OH-PAME by five
      bacteria was confirmed by High-Performance Liquid Chromatography-Mass
      Spectrometry analysis. 3OH-PAME degrading bacteria were identified as
      Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Rhodococcus
      corynebacterioides. 3OH-PAME degrading bacteria reduced the expression of
      virulence factors (exopolysaccharides and endoglucanase) of R. solanacearum in
      vitro and reduced wilt incidence in eggplant seedlings under greenhouse
      conditions. Isolates with quorum quenching activity successfully re-colonized
      eggplant seedlings. Quorum quenching bacteria produced antagonistic compounds,
      which may act synergistically with quorum quenching in reducing bacterial wilt in
      eggplant. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on
      endophytic bacteria of class Gammaproteobacteria and phylum Actinobacteria having
      3OH-PAME degrading activity. This study demonstrates the potential use of
      endophytic bacteria as quorum quenching biocontrol agents for management of
      bacterial wilt in eggplant.

PMID- 25580769
TI  - Flood adaptive traits and processes: an overview.
AB  - Unanticipated flooding challenges plant growth and fitness in natural and
      agricultural ecosystems. Here we describe mechanisms of developmental plasticity
      and metabolic modulation that underpin adaptive traits and acclimation responses
      to waterlogging of root systems and submergence of aerial tissues. This includes
      insights into processes that enhance ventilation of submerged organs. At the
      intersection between metabolism and growth, submergence survival strategies have
      evolved involving an ethylene-driven and gibberellin-enhanced module that
      regulates growth of submerged organs. Opposing regulation of this pathway is
      facilitated by a subgroup of ethylene-response transcription factors (ERFs),
      which include members that require low O2 or low nitric oxide (NO) conditions for
      their stabilization. These transcription factors control genes encoding enzymes
      required for anaerobic metabolism as well as proteins that fine-tune their
      function in transcription and turnover. Other mechanisms that control metabolism
      and growth at seed, seedling and mature stages under flooding conditions are
      reviewed, as well as findings demonstrating that true endurance of submergence
      includes an ability to restore growth following the deluge. Finally, we highlight
      molecular insights obtained from natural variation of domesticated and wild
      species that occupy different hydrological niches, emphasizing the value of
      understanding natural flooding survival strategies in efforts to stabilize crop
      yields in flood-prone environments.

PMID- 25580770
TI  - Evaluation of Photoprotective Potential and Percutaneous Penetration by
      Photoacoustic Spectroscopy of the Schinus terebinthifolius Raddi Extract.
AB  - Schinus terebinthifolius is a plant rich in phenolic compounds, which have
      antioxidant properties and can provide new opportunities for treatment and
      prevention of diseases mediated by ultraviolet radiation like photoaging and skin
      cancer. The aim of this study was to evaluate the photoprotective potential and
      ex vivo percutaneous penetration of the crude extract of Schinus terebinthifolius
      leaves. The extract was tested for antioxidant activity using the 2,2-diphenyl-1
      picrylhydrazyl (DPPH) method and beta-carotene bleaching test. The sun protection
      factor was also evaluated. The ex vivo skin permeation of the emulsion and gel
      formulations were assayed. Fractionation of the extract resulted in gallic acid,
      ethyl gallate and a mixture of flavonoids, suggesting derivatives of quercetin
      and myricetin. The phenolic content of the extract was 384.64 +/- 2.60 mg GAE g(
      1) extract. The antioxidant activity was superior to butylated hydroxytoluene, in
      DPPH method, and ascorbic acid and rutin, in beta-carotene bleaching assay. The
      extract showed UV absorption with photoprotector potential in the UVB region. The
      photoacoustic spectroscopy measurements confirmed absorption in the UV region and
      topical application of the formulations caused no histological changes in the
      rats' skin. These results suggest that the crude extract of Schinus
      terebinthifolius leaves may be a promising natural sunscreen product.

PMID- 25580771
TI  - Extent of secondary intraventricular hemorrhage is an independent predictor of
      outcomes in intracerebral hemorrhage: data from the Helsinki ICH Study.
AB  - BACKGROUND: Intraventricular hemorrhage is a severe subtype of intracerebral
      hemorrhage associated with high mortality and poor outcome. AIM: We analyzed
      various intraventricular hemorrhage scores at baseline to find common parameters
      associated with increased mortality. METHODS: Consecutive intracerebral
      hemorrhage patients treated in Helsinki University Central Hospital during 2005
      2010 were included in the Helsinki Intracerebral Hemorrhage Study registry and
      analyzed for three-month mortality. RESULTS: After excluding lost-to-follow-up
      patients, 967 intracerebral hemorrhage patients were included, out of whom 398
      (41%) had intraventricular hemorrhage. Intraventricular hemorrhage patients,
      compared with nonintraventricular hemorrhage patients, had lower baseline Glasgow
      Coma Scale [median 12 (IQR 6-15) vs. 15 (13-15); P < 0.001] and higher National
      Institutes of Health Stroke Scale [18 (10-27) vs. 7 (3-14); P < 0.001] scores;
      larger intracerebral hemorrhage volumes [17 ml (7.2-42) vs. 6.8 (2.4-18); P <
      0.001] and more often hydrocephalus (51% vs. 9%; P < 0.001); and higher mortality
      rates (54% vs. 18%; P < 0.001). In multivariable analysis, the presence of
      intraventricular hemorrhage was independently associated with mortality [OR 2.05
      (95% CI 1.36-3.09)] when adjusted for well-known prognostic factors of
      intracerebral hemorrhage, i.e. age, gender, baseline National Institutes of
      Health Stroke Scale, intracerebral hemorrhage volume, infratentorial location,
      and etiology. CONCLUSIONS: The presence of intraventricular hemorrhage was
      independently associated with increased mortality, and all the intraventricular
      hemorrhage scores were strong predictors of three-month mortality.

PMID- 25580772
TI  - Optimal design in pediatric pharmacokinetic and pharmacodynamic clinical studies.
AB  - It is not trivial to conduct clinical trials with pediatric participants.
      Ethical, logistical, and financial considerations add to the complexity of
      pediatric studies. Optimal design theory allows investigators the opportunity to
      apply mathematical optimization algorithms to define how to structure their data
      collection to answer focused research questions. These techniques can be used to
      determine an optimal sample size, optimal sample times, and the number of samples
      required for pharmacokinetic and pharmacodynamic studies. The aim of this review
      is to demonstrate how to determine optimal sample size, optimal sample times, and
      the number of samples required from each patient by presenting specific examples
      using optimal design tools. Additionally, this review aims to discuss the
      relative usefulness of sparse vs rich data. This review is intended to educate
      the clinician, as well as the basic research scientist, whom plan on conducting a
      pharmacokinetic/pharmacodynamic clinical trial in pediatric patients. 

PMID- 25580773
TI  - Cytomorphological characteristics of low-grade papillary urothelial carcinoma for
      differential diagnosis from benign papillary urothelial lesions: logistic
      regression analysis in SurePath(TM) liquid-based voided urine cytology.
AB  - OBJECTIVE: The diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in
      urine cytology specimens is challenging because of its subtle, minimally atypical
      findings. Furthermore, as SurePath(TM) liquid-based cytology (LBC) is becoming a
      widely used method in urine cytology, the inevitable cytomorphological
      alterations resulting from this technique call for new morphological diagnostic
      criteria in LGPUC. METHODS: Logistic regression analysis was carried out on
      SurePath slides from surgically proven voided urine specimens. The study was
      designed to include a test set (n = 141) and a validation set (n = 61), and
      evaluated significant discriminative parameters between LGPUC and benign
      papillary urothelial neoplasm (BPUN). RESULTS: Of the seven cytological findings
      that were found to have statistical significance in univariate analysis, five
      were found to be independent variables: loss of polarity of papillaroid clusters,
      irregular contours, absence of columnar cells, hobnail features and
      hyperchromasia. These independent variables had an area under the curve (AUC) of
      0.781. CONCLUSIONS: The distinctive cytological criteria identified above may
      prove to be helpful in cases in which other conventional criteria for LGPUC are
      insufficient for diagnosis.

PMID- 25580774
TI  - Impacts of sporulation temperature, exposure to compost matrix and temperature on
      survival of Bacillus cereus spores during livestock mortality composting.
AB  - AIMS: To investigate impact of sporulation and compost temperatures on
      feasibility of composting for disposal of carcasses contaminated with Bacillus
      anthracis. METHODS AND RESULTS: Two strains of B. cereus, 805 and 1391, were
      sporulated at either 20 or 37 degrees C (Sporulation temperature, ST) and 7 Log10
      CFU g(-1) spores added to autoclaved manure in nylon bags (pore size 50 MUm) or
      in sealed vials. Vials and nylon bags were embedded into compost in either a
      sawdust or manure matrix each containing 16 bovine mortalities (average weight
      617 +/- 33 kg), retrieved from compost at intervals over 217 days and survival of
      B. cereus spores assessed. A ST of 20 degrees C decreased spore survival by 1.4
      log10 CFU g(-1) (P < 0.05) compared to a 37 degrees C ST. Spore survival was
      strain dependent. Compost temperatures >55 degrees C reduced spore survival (P <
      0.05) and more frequently occurred in the sawdust matrix. CONCLUSIONS:
      Sporulation and compost temperatures were key factors influencing survival of B.
      cereus spores in mortality compost. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Composting may be most appropriate for the disposal of carcasses infected with B.
      anthracis at ambient temperatures <=20 degrees C under thermophillic composting
      conditions (>55 degrees C).

PMID- 25580777
TI  - Focused particle beam nano-machining: the next evolution step towards simulation
      aided process prediction.
AB  - During the last decade, focused ion beam processing has been developed from
      traditionally used Ga(+) liquid ion sources towards higher resolution gas field
      ion sources (He(+) and Ne(+)). Process simulations not only improve the
      fundamental understanding of the relevant ion-matter interactions, but also
      enable a certain predictive power to accelerate advances. The historic 'gold'
      standard in ion-solid simulations is the SRIM/TRIM Monte Carlo package released
      by Ziegler, Ziegler and Biersack 2010 Nucl. Instrum. Methods B 268 1818-23. While
      SRIM/TRIM is very useful for a myriad of applications, it is not applicable for
      the understanding of the nanoscale evolution associated with ion beam nano
      machining as the substrate does not evolve with the sputtering process. As a
      solution for this problem, a new, adapted simulation code is briefly overviewed
      and finally addresses these contributions. By that, experimentally observed Ne(+)
      beam sputter profiles can be explained from a fundamental point of view. Due to
      their very good agreement, these simulations contain the potential for computer
      aided optimization towards predictable sputter processes for different
      nanotechnology applications. With these benefits in mind, the discussed
      simulation approach represents an enormous step towards a computer based master
      tool for adaptable ion beam applications in the context of industrial
      applications. 

PMID- 25580775
TI  - Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2
      diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group,
      active-controlled, phase III clinical trial with a 28-week extension.
AB  - We aimed to compare the efficacy and safety of lobeglitazone and pioglitazone as
      add-ons to metformin in patients with type 2 diabetes. Patients who were
      inadequately controlled by metformin were randomized and treated once daily with
      either lobeglitazone (0.5 mg, n = 128) or pioglitazone (15 mg, n = 125) for 24
      weeks, with a 28-week extension trial of lobeglitazone treatment in patients who
      consented. The primary endpoint was the change in glycated haemoglobin (HbA1c)
      concentration from baseline to week 24. At week 24, the mean change from baseline
      in HbA1c was -0.74% for the lobeglitazone group and -0.74% for the pioglitazone
      group, with a mean difference of 0.01% [95% confidence interval (CI) of
      difference, -0.16 to 0.18]. The effects of lobeglitazone on lipid variables and
      the adverse events associated with lobeglitazone were similar to those observed
      with pioglitazone. Lobeglitazone was not inferior to pioglitazone as an add-on to
      metformin in terms of their efficacy and safety. 

PMID- 25580776
TI  - 'It's something you have to put up with'--service users' experiences of in utero
      transfer: a qualitative study.
AB  - OBJECTIVE: The purpose of this study was to gain in-depth insight and enhance
      understanding of service users' experiences of the in utero transfer (IUT)
      process, in order to inform policy and improve the current service provision of
      maternal care. DESIGN: Qualitative descriptive study using semi-structured
      interviews. SETTING: Participant's home or hospital in the Midlands, UK.
      POPULATION: Fifteen women transferred in utero to a tertiary level maternity
      hospital; five male partners and two grandmothers. METHODS: Audio-recorded
      individual or paired semi-structured interviews transcribed verbatum and analysed
      thematically using nvivo 9. MAIN OUTCOME MEASURES: Facilitators and barriers of
      the IUT experience. RESULTS: Findings suggest that IUT is an emotional experience
      that financially disadvantages patients and their families. Male partners were
      perceived to be most negatively affected by the experience. The quality of the
      IUT experience was influenced by a range of factors, including the lack of
      proximity to home and the lack of information. Patients had little knowledge or
      awareness of IUT, and most felt unprepared for displacement. Despite this, there
      was resigned acceptance that IUT was a necessary rather than adverse experience.
      CONCLUSIONS: The experience of IUT for service users could be enhanced by
      ensuring that they are better informed about the process and the circumstances
      that necessitate displacement, that they are better informed about the hospital
      to which they are being transferred, and that they are transferred as close to
      home as possible. Efforts to minimise the emotional and socio-economic impact of
      IUT on women and their families also need to be considered.

PMID- 25580778
TI  - Deliberate malfeasance or innocent error? Misrepresentation in pain medicine
      fellowship applications.

PMID- 25580779
TI  - Primary succession of Bistorta vivipara (L.) Delabre (Polygonaceae) root
      associated fungi mirrors plant succession in two glacial chronosequences.
AB  - Glacier chronosequences are important sites for primary succession studies and
      have yielded well-defined primary succession models for plants that identify
      environmental resistance as an important determinant of the successional
      trajectory. Whether plant-associated fungal communities follow those same
      successional trajectories and also respond to environmental resistance is an open
      question. In this study, 454 amplicon pyrosequencing was used to compare the root
      associated fungal communities of the ectomycorrhizal (ECM) herb Bistorta vivipara
      along two primary succession gradients with different environmental resistance
      (alpine versus arctic) and different successional trajectories in the vascular
      plant communities (directional replacement versus directional non-replacement).
      At both sites, the root-associated fungal communities were dominated by ECM
      basidiomycetes and community composition shifted with increasing time since
      deglaciation. However, the fungal community's successional trajectory mirrored
      the pattern observed in the surrounding plant community at both sites: the alpine
      site displayed a directional-replacement successional trajectory, and the arctic
      site displayed a directional-non-replacement successional trajectory. This
      suggests that, like in plant communities, environmental resistance is key in
      determining succession patterns in root-associated fungi. The need for further
      replicated study, including in other host species, is emphasized. 

PMID- 25580780
TI  - RAS mutation status and bortezomib therapy for relapsed multiple myeloma.

PMID- 25580781
TI  - Anti-neutrophil cytoplasmic antibody positivity in five children with systemic
      lupus erythematosus--what is the importance of this finding?
AB  - Juvenile systemic lupus erythematosus (JSLE) is a systemic autoimmune chronic
      disease that can affect any part of the body. It is characterized by the
      formation of antibodies against nuclear antigens. Vasculitis may be found in SLE,
      but it scarcely complies with anti-neutrophil cytoplasmic antibodies (ANCA)
      associated vasculitis (AAV) criteria. We report five cases of severe JSLE
      associated with AAV diagnosed between 1991 and 2013 in three university-based
      tertiary care centers. The patients (3 girls and 2 boys, aged 12 to 17) presented
      with a severe clinical picture and the following features: cytopenia (n=5),
      autoimmune hepatitis (n=3), lupus nephritis (n=1), pancreatitis (n=1), secondary
      antiphospholipid syndrome (n=2), impending respiratory failure (n=2), and
      gastrointestinal bleeding (n=1). All patients were proteinase 3 (PR3) ANCA
      positive, while two of them were myeloperoxidase (MPO) and PR3 ANCAs positive at
      the same time. They were treated with corticosteroids and immunosuppressive
      drugs. Remission of the disease was achieved in three patients. The course of the
      disease was worsening in two patients and we included rituximab (anti-CD20) in
      therapy. All of our patients presented as the most severe SLE patients, who must
      be diagnosed as soon as possible and treated very intensively. Since the
      comorbidity of JSLE and AAV occurs very rarely in children, presentation of such
      patients, their clinical pictures, treatment, and the course of the diseases are
      experiences that can be of great help.

PMID- 25580782
TI  - Association of interleukin 10 and transforming growth factor beta gene
      polymorphisms with chronic idiopathic urticaria.
AB  - Transforming growth factor beta (TGF-beta) and interleukin 10 (IL-10) are two
      anti-inflammatory cytokines that are implicated in the pathogenesis of urticaria.
      The goal of this study was to examine the possible association of polymorphisms
      of TGF-beta and IL-10 genes with susceptibility to chronic idiopathic urticaria
      (CIU). This study was conducted on 90 patients with CIU. Polymerase chain
      reaction (PCR) was done to determine the genotype at 5 polymorphic sites; TGF
      beta (codon10C/T and codon25G/C) and IL-10 (-1082G/A, -819C/T, and -592C/A). The
      C allele at codon 25 of TGF-beta was more prevalent in CIU patients compared to
      controls (OR = 9.5, 95% CI = 5.4-16.8, P<0.001). Genotypes of CT and CG at 10 and
      25 codons of TGF-beta gene, respectively, and AG, CT, and CA for loci of -1082, 
      819, and -592 of IL-10 gene were significantly higher in CIU patients (P<0.001).
      In haplotype analysis, frequency of TGF-beta haplotypes differed between patients
      with CIU and controls; CC haplotype was overrepresented, while CG and TG
      haplotypes were underrepresented (P<0.001). These results suggest that TGF-beta
      and IL-10 genetic variability could contribute to susceptibility to CIU.
      Additionally, patients with CIU seem to have genotypes leading to high production
      of TGF-beta and IL-10. 

PMID- 25580783
TI  - Epidemiology of autoimmune bullous diseases and therapeutic modalities during a
      10 year period in Iran.
AB  - Autoimmune bullous diseases are systemic disorders with autoantibodies that
      result in blisters. Aim of this study was to indicate the spectrum and treatment
      modalities of five types of bullous disorders most prevalent in the south of
      Iran: pemphigus vulgaris (PV), pemphigus foliaceus (PF), epidermolysis bullousa
      aquisita (EBA), bullous pemphigoid (BP), and pemphigoid gestationis (PG).
      Patients with PV, PF, BP, EBA, and PG were included in this study. The data
      regarding the age, sex, and the treatment used for PV, PF, and BP were recorded
      and analyzed in our center, a tertiary referral center. T-test and Mann-Whitney
      test for independent samples were used for the analysis of parametric and
      nonparametric variables, respectively. Chi-square test was used for frequencies.
      Of the 441 patients included in this study, 82.9% had PV, 4.7% PF, 8.5% BP, 1.5%
      EBA, and 1.3% PG. 93.5% of patients with PV, 95.3% with PF, and 100% with
      patients with BP were treated and responded to first line therapies with one or
      two medications. The most frequent autoimmune bullous disease was PV, followed by
      PF. For PV and PF, combination of prednisolone and azathioprine was the most
      frequent first line medication. In the patients with BP, prednisolone monotherapy
      was the most frequent one. Only a minority of patients with PV and PF needed the
      third or fourth medications.

PMID- 25580785
TI  - Specialists are not qualified enough to recognize and define dermatologic
      diseases.
AB  - Dermatology is a specific branch of medicine which includes dermatologic
      manifestations of systemic underlying diseases as well as primary cutaneous
      diseases. In this study, specialists' abilities of defining and diagnosing
      dermatologic diseases were assessed. 381 hospitalized patients who were referred
      to the Dermatology Clinic were reviewed via electronic medical charts. 121 of the
      clinicians (31.2%) made a dermatologic definition when referring their patients
      to dermatology. 136 of the the clinicians (35.1%) made a pre-diagnosis for their
      patients' dermatologic condition of which 90 (66,2%) were correct and 46 (33,8%)
      were non-relevant. Internists wrote a definitive dermatologic examination note
      significantly more often than surgeons (P=0.03). However, there was not a
      significant difference between internists and surgeons when we compared the ratio
      of correct and complete dermatologic definitions of patient condition (P=0.503).
      There was also no difference between surgeons and internists in terms of making a
      pre-diagnosis, making a correct diagnosis, and making a wrong diagnosis (P>0.05
      for each comparison). In conclusion, dermatologic consultations are crucial and
      necessary for the improvement of patient care and treatment. Specialists lack
      basic skills to recognize and define dermatologic conditions they are confronted
      with. 

PMID- 25580784
TI  - NAVS naphthalan for the treatment of oral mucosal diseases--a pilot study.
AB  - "Non-Aromatic Very rich in Steranes" (NAVS) naphthalan is a purified natural oil
      derivative, abundant in steranes (geogenic "steroids"). The purpose of this study
      was to evaluate the effectiveness of NAVS in the treatment of oral lichen planus
      (OLP) and recurrent aphthous stomatitis (RAS). We used NAVS oil in adhesive paste
      in 11 patients with clinically and histologically proven OLP (open label), and in
      7 patients with RAS (double blind randomized; topical betamethasone in adhesive
      paste used as control). The severity of the OLP lesions was objectively scored.
      The number and diameter of RAS lesions were assessed on days 0, 3, and 5. The
      intensity of pain and discomfort was determined using visual analogue scale (VAS)
      and "Oral health impact profile" (OHIP-14) before and after therapy. OLP
      cumulative activity scores on days 0 and 28 were 101.5 and 48.5, respectively
      (t=5.99; P=0.0001). Using NAVS for 28 days resulted in 52.2% overall clinical
      improvement. Cumulative OHIP-14 scores on days 0 and 28 were 210 and 142,
      respectively (t=5.65; P=0.0002). Out of a total of 7 patients with RAS, 4 of them
      were treated with NAVS and 3 with topical corticosteroids. There were no
      statistically significant differences in improvement rate between the two groups
      (lesion number (day 3 P=0.29; day 5 P=0.32); lesion diameter (day 3 P=0.64; day 5
      P=0.74)). NAVS successfully reduced the clinical signs and symptoms of OLP, and
      reduced the number, diameter, and symptoms in patients with RAS, statistically
      comparable with corticosteroids. 

PMID- 25580786
TI  - Clinical and morphological characteristics of cutaneous melanoma.
AB  - The incidence of cutaneous melanoma has increased significantly worldwide over
      the last several decades. The aim of this study is to determine clinical and
      morphology characteristics of primary melanoma, since some of them are important
      prognostic factors. This retrospective study included 172 patients. The data were
      collected by the Consulting team for malignant skin tumors in the Banja Luka
      Clinical Centre from 2009 to 2011. We did not use dermoscopy as a diagnostic tool
      in our investigation. We determined that melanoma occurs equally commonly in both
      sexes, in women in the sixth decade and the seventh in men. The most common sub
      type was nodular melanoma (59.5%, P<0.05), followed by superficial spreading
      (27.8%) and acral lentiginous melanoma (11.4%). The most common localization was
      on the back in men (34.3%) and on the legs in women (P<0.05). More than half of
      our patients (55.8%) had melanoma thickness from 1.0 to 4.0 mm, and 38% had a
      melanoma thicker than 4.0 mm. The average Breslow thickness is 4.6 mm. More women
      than men had melanoma thicker than 4 mm (P<0.05). Spread of the primary tumor
      localization was found in 31.4% of patients, more frequently in men than in women
      (P<0.05). In most cases it was abstraction of lymph nodes (P<0.05). The average
      thickness of the melanoma in our patients is much higher than the average in the
      world and the countries of Europe. The results of this study indicate a need for
      better unique regional registry in this part of Bosnia and Herzegovina and
      improvement of preventive measures in the early diagnosis of melanoma. 

PMID- 25580787
TI  - Pitfalls of an automated dermoscopic analysis system in the differential
      diagnosis of melanocytic lesions.
AB  - Dermoscopy plays an important role in the diagnosis of pigmented lesions,
      particularly in the differential diagnosis of early-stage melanoma. Dermoscopy
      systems that aim to enable automatic "unmanned-without physician" diagnosis are
      becoming increasingly common. We aimed to investigate the reliability and
      weaknesses of diagnosis programs. Furthermore, we attempted to determine whether
      such programs are superior to diagnosis by a physician, compared to
      histopathological assessment. The images stored in the DermoGenius ultra
      computerized dermoscopy system of the Dermoscopy Unit between January 2008 and
      December 2008 were surveyed retrospectively. Dermoscopic images made prior to
      excision of 77 lesions from 51 patients verified by histopathology were reviewed.
      Nineteen patients were men and 32 were women. Mean age was 35.5 years. Diagnosis
      by a clinician or automatic analysis revealed that 23 (30%) of the lesions were
      atypical (dysplastic) nevi, 22 (29%) were compound nevi, 10 (13%) were dermal
      nevi, 8 (10%) were malignant melanomas, 7 (9%) were common nevi, 6 (7%) were
      junctional nevi, and 1 (1%) was a blue nevus. Compared to histopathological
      diagnosis, considered the gold standard, the sensitivity of the automated
      analysis program was 96.6%, its specificity 14.9%, and its diagnostic accuracy
      47%. For the clinician, the values were 100% for sensitivity, 66.7% for
      specificity, and 95% for diagnostic accuracy. Based on histopathological results,
      the diagnostic accuracy of the physician was higher than that of the automatic
      analysis program. Therefore, errors are inevitable when an inexperienced
      physician assesses patients according to automatic program results. 

PMID- 25580788
TI  - Fuchs' syndrome (Stevens-Johnson syndrome without skin involvement) in an adult
      male--a case report and general characteristics of the sporadically diagnosed
      disease.
AB  - Fuchs' syndrome (Stevens-Johnson syndrome without skin involvement) is a
      sporadically diagnosed disease. Most authors consider it to be a pure mucosal
      variant of Stevens-Johnson syndrome; however, some consider the syndrome a
      separate entity. The complete absence of cutaneous symptoms may be the reason
      that not all cases of Fuchs' syndrome are diagnosed and properly classified. The
      authors describe a case of a 22-year-old patient suffering only from mucosal
      symptoms, diagnosed as Fuchs' syndrome from the context of the tests performed. A
      Mycoplasma pneumoniae infection triggered the disease onset. Mycoplasma
      infection, as a trigger factor of Fuchs' syndrome in adults, has so far been
      described in only a few isolated cases worldwide. 

PMID- 25580789
TI  - Resolution of a case of pediatric pemphigus vulgaris treated with rituximab.
AB  - Pemphigus vulgaris (PV) is an infrequent autoimmune bullous disease involving the
      skin and mucous membranes, which is rare in pediatrics. Although the main therapy
      for childhood PV are steroids, immunosuppressive drugs are often needed to
      control the disease. We report the case of an 11-year-old Caucasian boy who
      presented with a 10 months history of PV unresponsive to steroids and to
      intravenous immunoglobulin. The therapeutic use of rituximab allowed a long
      lasting and complete remission. According to a good safe profile and to our case
      report, as well as the literature, rituximab may be considered an safe and
      efficacious treatment for PV. 

PMID- 25580790
TI  - Adalimumab treatment for hidradenitis suppurativa associated with Crohn's
      disease.
AB  - Hidradenitis suppurativa (HS) is a chronic, inflammatory disease characterized by
      recurring abscesses, nodules, and fistulas predominantly in the area of the groin
      and axillae. The association between HS and Crohn's disease (CD) has already been
      documented. We report on a case of a patient with CD associated HS, refractory to
      multiple local and systemic agents.A complete resolution of both diseases was
      finally achieved after treatment with adalimumab. Our case report supports the co
      occurrence of both diseases and suggests that adalimumab approved for CD might
      also be a safe and effective therapeutic option in the treatment of HS.

PMID- 25580791
TI  - Bacillary angiomatosis in a HIV-positive patient with poor adherence to
      antiretroviral therapy.
AB  - Bacillary angiomatosis is a systemic disease caused by Bartonella (B.) henselae
      and B. quintana. Today it is a rare disease that occurs predominantly in patients
      with poor adherence to antiretroviral therapy or with late diagnosis of human
      immunodeficiency virus (HIV). We report on the case of a 40-year-old Caucasian
      female with HIV-1 and hepatitis B virus (HBV) co-infection diagnosed 17 years
      ago. She presented to the emergency department with an erythematous, painless
      nodule located on the left naso-genian fold. In the next few weeks the disease
      disseminated to the oral and left tarsal mucosa and to the palm of the left hand.
      The histopathological findings were suggestive of bacillary angiomatosis which
      was confirmed by polymerase chain reaction (PCR). The patient was treated with
      clarithromycin 500 mg bid per os for 3 months, with complete remission of the
      mucocutaneous lesions. Bacillary angiomatosis is a potentially fatal disease.
      Early diagnosis and treatment are critical in reducing the morbidity and
      mortality associated with it. 

PMID- 25580792
TI  - Group G Streptococcus bacteremia in recurrent cellulitis.
AB  - In recent years, group G Streptococcus has been reported with increasing
      frequency as the cause of a variety of human infections. Underlying host factors
      such as immunosuppression, malignancy, diabetes mellitus, and rheumatoid
      arthritis may be predisposing conditions leading to infection. Toxic involvement
      and post-streptococcal sequalae, once believed to be exclusive to infections
      caused by group A Streptococcus, are now known to occur following acute group G
      Streptococcus and group C Streptococcus infections. We report on a case of group
      G Streptococcus bacteremia and recurrent cellulitis with toxic involvement.
      Patient blood cultures were always negative for beta-hemolytic Streptococci in
      all the recurrences, except during the last one. Antibiotic therapy based on
      antibiogram quickly resolved the infection. A regimen of intramuscular injection
      of 1.2 million units of benzathine penicillin every 15 days for one year
      prevented recurrences of cellulitis. 

PMID- 25580793
TI  - PUVA induced bullous pemphigoid in a patient with psoriasis.

PMID- 25580794
TI  - Granuloma faciale effectively treated with topical pimecrolimus.

PMID- 25580795
TI  - Multiple primary cutaneous plasmacytoma.

PMID- 25580796
TI  - Atypical pearly penile papules mimicking primary syphilis.

PMID- 25580797
TI  - What is new and hot in genetics of human atopic dermatitis: shifting paradigms in
      the landscape of allergic skin diseases.

PMID- 25580798
TI  - Radiation-Induced Chemical Changes to Iron Oxides.
AB  - The radiolysis of a variety of iron oxide powders with different amounts of
      associated water has been performed using gamma rays and 5 MeV (4)He ions.
      Adsorbed water was characterized by both temperature-programmed desorption and
      diffuse reflection infrared Fourier transform spectroscopy to reveal a variety of
      active sites on the surface. Molecular hydrogen production was found only from
      water adsorbed on Fe2O3, and the yield was several orders of magnitude greater
      than that of bulk water. Aqueous slurries of FeO, Fe3O4, and Fe2O3 examined as a
      function of water fraction gave different yields of H2 depending on the oxide
      type and the amount of water. Examination of the iron oxide powders following
      irradiation by X-ray diffraction showed no change in crystal structure. Raman
      spectroscopy of the oxides revealed the formation of islands of Fe2O3 on the
      surfaces of FeO and Fe3O4. X-ray photoelectron spectroscopy of the oxides
      revealed the general formation of oxygen species following radiolysis. 

PMID- 25580799
TI  - Oral and maxillofacial pathologies in young- and middle-aged adults.
AB  - OBJECTIVE: To evaluate the distribution of oral and maxillofacial pathologies
      (OMFPs) and its association with patient age in young- and middle-aged adults.
      METHODS: Distribution of histopathologically diagnosed OMFPs (n = 385) treated
      during 2007-2010 was recorded and the association with patient age was
      retrospectively analyzed. RESULTS: The main diagnostic categories included benign
      exophytic lesions (45.3%), white benign lesions (13.5%), potentially malignant
      lesions/disorders (10.1%), intrabony lesions (9.8%), mucosal discoloration
      (7.8%), benign pigmented lesions (7.3%), chronic trauma/inflammation (3.9%), and
      oral malignancy (2.1%). Potentially malignant lesions/disorders as a diagnostic
      category were positively associated with age (OR = 1.07 for 1 year; P < 0.001)
      and specifically the diagnoses of oral lichen planus (OR = 1.04 for 1 year; P =
      0.037) and dysplastic changes (OR = 1.08 for 1 year; P = 0.013) that comprised
      this category. Pigmented melanocytic lesions were negatively associated with age
      (OR = 0.94 for 1 year; P = 0.039) as well as benign/reactive exophytic lesions
      (OR = 0.98 for 1 year; P = 0.038), the latter included the histopathological
      diagnosis of benign salivary gland pathologies (OR = 0.90 for 1 year; P < 0.001).
      CONCLUSION: This study provided baseline information regarding the distribution
      OMFPs among young- and middle-aged adults. It is important to highlight the high
      frequency of potentially malignant lesions/disorders and oral malignancy in young
      and middle-aged adults, as these lesions require lifelong follow-up.

PMID- 25580800
TI  - Benchmarking Compound Methods (CBS-QB3, CBS-APNO, G3, G4, W1BD) against the
      Active Thermochemical Tables: A Litmus Test for Cost-Effective Molecular
      Formation Enthalpies.
AB  - The theoretical atomization energies of some 45 CxHyOz molecules present in the
      Active Thermochemical Tables compilation and of particular interest to the
      combustion chemistry community have been computed using five composite model
      chemistries as titled. The species contain between 1-8 "heavy" atoms, and a few
      are conformationally diverse with up to nine conformers. The enthalpies of
      formation at 0 and 298.15 K are then derived via the atomization method and
      compared against the recommended values. In general, there is very good agreement
      between our averaged computed values and those in the ATcT; those for 1,3
      cyclopentadiene exceptionally differ considerably, and we show from isodesmic
      reactions that the true value for 1,3-cyclopentadiene is closer to 134 kJ mol(-1)
      than the reported 101 kJ mol(-1). If one is restricted to using a single method,
      statistical measures indicate that the best methods are in the rank order G3 ~ G4
      > W1BD > CBS-APNO > CBS-QB3. The CBS-x methods do on average predict
      DeltafH(?)(298.15 K) within ~5 kJ mol(-1) but are prone to occasional lapses.
      There are statistical advantages to be gained from using a number of methods in
      tandem, and all possible combinations have been tested. We find that the average
      formation enthalpy coming from using CBS-APNO/G4, CBS-APNO/G3, and G3/G4 show
      lower mean signed and mean unsigned errors, and lower standard and root-mean
      squared deviations, than any of these methods in isolation. Combining these
      methods also leads to the added benefit of providing an uncertainty rooted in the
      chemical species under investigation. In general, CBS-APNO and W1BD tend to
      underestimate the formation enthalpies of target species, whereas CBS-QB3, G3,
      and G4 have a tendency to overestimate the same. Thus, combining CBS-APNO with a
      G3/G4 combination leads to an improvement in all statistical measures of accuracy
      and precision, predicting the ATcT values to within 0.14 +/- 4.21 kJ mol(-1),
      thus rivalling "chemical accuracy" (+/-4.184 kJ mol(-1)) without the excessive
      cost associated with higher-level methods such as W1BD. 

PMID- 25580801
TI  - High-efficiency, low turn-on voltage blue-violet quantum-dot-based light-emitting
      diodes.
AB  - We report high-efficiency blue-violet quantum-dot-based light-emitting diodes (QD
      LEDs) by using high quantum yield ZnCdS/ZnS graded core-shell QDs with proper
      surface ligands. Replacing the oleic acid ligands on the as-synthesized QDs with
      shorter 1-octanethiol ligands is found to cause a 2-fold increase in the electron
      mobility within the QD film. Such a ligand exchange also results in an even
      greater increase in hole injection into the QD layer, thus improving the overall
      charge balance in the LEDs and yielding a 70% increase in quantum efficiency.
      Using 1-octanethiol capped QDs, we have obtained a maximum luminance (L) of 7600
      cd/m(2) and a maximum external quantum efficiency (etaEQE) of (10.3 +/- 0.9)%
      (with the highest at 12.2%) for QD-LEDs devices with an electroluminescence peak
      at 443 nm. Similar quantum efficiencies are also obtained for other blue/violet
      QD-LEDs with peak emission at 455 and 433 nm. To the best of our knowledge, this
      is the first report of blue QD-LEDs with etaEQE > 10%. Combined with the low turn
      on voltage of ~2.6 V, these blue-violet ZnCdS/ZnS QD-LEDs show great promise for
      use in next-generation full-color displays. 

PMID- 25580803
TI  - Influence of Intracranial Electrode Density and Spatial Configuration on
      Interictal Spike Localization: A Case Study.
AB  - PURPOSE: Poor seizure outcomes after epilepsy surgery often reflect an incorrect
      localization of the epileptic sources by standard intracranial EEG interpretation
      because of limited electrode coverage of the epileptogenic zone. This study
      investigates whether, in such conditions, source modeling is able to provide more
      accurate source localization than the standard clinical method that can be used
      prospectively to improve surgical resection planning. METHODS: Suboptimal
      epileptogenic zone sampling is simulated by subsets of the electrode
      configuration used to record intracranial EEG in a patient rendered seizure free
      after surgery. sLORETA and the clinical method solutions are applied to
      interictal spikes sampled with these electrode subsets and are compared for
      colocalization with the resection volume and displacement due to electrode
      downsampling. RESULTS: sLORETA provides often congruent and at times more
      accurate source localization when compared with the standard clinical method.
      However, with electrode downsampling, individual sLORETA solution locations can
      vary considerably and shift consistently toward the remaining electrodes.
      CONCLUSIONS: sLORETA application can improve source localization based on the
      clinical method but does not reliably compensate for suboptimal electrode
      placement. Incorporating sLORETA solutions based on intracranial EEG in surgical
      planning should proceed cautiously in cases where electrode repositioning is
      planned on clinical grounds.

PMID- 25580802
TI  - Quantitative EEG is an objective, sensitive, and reliable indicator of transient
      anesthetic effects during Wada tests.
AB  - The intracarotid amobarbital or Wada procedure is a component of the presurgical
      evaluation for refractory epilepsy, during which monitoring the onset and offset
      of transient anesthetic effects is critical. In this study, the authors
      characterized changes of 8 quantitative measures during 26 Wada tests, which
      included alpha, beta, theta, and delta powers, alpha/delta power ratio,
      beta/delta power ratio, median amplitude-integrated EEG, and 90% spectral edge
      frequency (SEF90), and correlated them with contralateral hemiplegia. The authors
      found that on the side of injection, delta and theta powers, alpha/delta power
      ratio, beta/delta power ratio, and SEF90 peaked within 1 minute after injection
      of 70 to 150 mg amobarbital or 4 to 7 mg methohexital. When contralateral arm
      strength returned to 3/5, delta power and amplitude-integrated EEG decayed on
      average 24% and 19%, respectively, for amobarbital, similar to that of
      methohexital (27% and 18%). Because delta power resolution most closely mirrored
      that of the hemiplegia and amplitude-integrated EEG had the highest signal/noise
      ratio, these quantitative values appear to be the best measures for decay of
      anesthetic effects. Increase in alpha power persisted longest, and therefore may
      be the best measure of late residual anesthetic effects. 

PMID- 25580804
TI  - E-norms: a method to extrapolate reference values from a laboratory population.
AB  - PURPOSE: Collecting reference values in subpopulations such as infants and
      children can pose a daunting challenge to gather through epidemiologic studies.
      The authors propose to evaluate a method the authors refer to as extrapolated
      norms (e-norms) to derive Stimulated Single Fiber EMG jitter reference values
      from the laboratory data of pediatric and adult cohorts. Single Fiber EMG studies
      are considered the gold standard test for evaluation of neuromuscular
      transmission disorders. METHODS: Data that lie in the plateau part of an inverted
      S curve derived from sorted jitter data were used to calculate descriptive
      statistics for pediatric and adult e-norms jitter. RESULTS: The e-norms derived
      jitter was 22 +/- 2.83 MUs for our pediatric and 21 +/- 2.79 MUs for our adult
      cohort. Our adult e-norms values compared favorably with the 22 +/- 1.99 MUs
      published jitter range derived from a healthy adult cohort. CONCLUSIONS: The e
      norms method the authors describe seems to be useful in recovering reference
      ranges when such values are difficult to obtain, such as in a pediatric
      subpopulation.

PMID- 25580805
TI  - Interplay of interleukin-22 and its binding protein in controlling liver
      scarring.

PMID- 25580806
TI  - One-step sonoelectrochemical fabrication of gold nanoparticle/carbon nanosheet
      hybrids for efficient surface-enhanced Raman scattering.
AB  - A simple, fast, reproducible and efficient one-step fabrication method was
      successfully developed to prepare gold nanoparticle/carbon nanosheet (Au NP/CNS)
      hybrids by using sonoelectrochemistry. This method involved simultaneous
      generation of carbon nanosheets (CNSs) by oxidation of a graphite anode and
      generation of Au NPs by reduction of AuCl4(-) on the surface of the cathode. Then
      the Au NPs modified with poly(diallyl dimethyl ammonium chloride) were self
      assembled on the surface of the CNS. A homemade sonoelectrochemical device that
      provided both high-intensity electric and ultrasonic fields was applied. The
      ability to obtain Au NPs with a controlled size and distribution on the surface
      of the CNS benefitted from the synergistic effect of the electric field and
      ultrasonic field. The Au NPs on the CNS surface exhibited distinctive and high
      quality SERS activity. The enhancement factor of the developed substrate was 1.2
      * 10(6) using 4-aminothiophenol as the probe molecule. The Au NP/CNS hybrid
      showed a great increase of Raman signals for aromatic molecules because of the
      high affinity of the CNS for aromatic molecules and the SERS activity of Au NPs.
      This SERS substrate also showed charge selectivity for cationic aromatic dyes,
      due to the negative charge on the surface of the CNS. Subsequently, the potential
      practical application of the SERS substrate was evaluated by quantitative
      analysis of adenine. The results suggest that Au NP/CNS materials as sensitive
      SERS-active substrates have great potential for detection of biomolecules. 

PMID- 25580807
TI  - Enantioselective rhodium-catalyzed isomerization of 4-iminocrotonates: asymmetric
      synthesis of a unique chiral synthon.
AB  - An enantioselective isomerization of 4-iminocrotonates catalyzed by a
      rhodium(I)/phosphoramidite complex is described. This reaction uses widely
      available amines to couple with 4-oxocrotonate to provide a convenient access to
      a central chiral building block in good yield and high enantioselectivity.
      Although the mechanism of this new transformation remains unclear, both Rh and
      the phosphoramidite play a central role. 

PMID- 25580808
TI  - Evaluation of Gd-DTPA-monophytanyl and phytantriol nanoassemblies as potential
      MRI contrast agents.
AB  - Supramolecular self-assembling amphiphiles have been widely used in drug delivery
      and diagnostic imaging. In this report, we present the self-assembly of Gd (III)
      chelated DTPA-monophytanyl (Gd-DTPA-MP) amphiphiles incorporated within
      phytantriol (PT), an inverse bicontinuous cubic phase forming matrix at various
      compositions. The dispersed colloidal nanoassemblies were evaluated as potential
      MRI contrast agents at various magnetic field strengths. The homogeneous
      incorporation of Gd-DTPA-MP in PT was confirmed by polarized optical microscopy
      (POM) and synchrotron small-angle X-ray scattering (SAXS) of the bulk phases of
      the mixtures. The liquid crystalline nanostructures, morphology, and the size
      distribution of the nanoassemblies were studied by SAXS, cryogenic transmission
      electron microscopy (cryo-TEM), and dynamic light scattering (DLS). The
      dispersions with up to 2 mol % of Gd-DTPA-MP in PT retained inverse cubosomal
      nanoassemblies, whereas the rest of the dispersions transformed to liposomal
      nanoassemblies. In vitro relaxivity studies were performed on all the dispersions
      at 0.54, 9.40, and 11.74 T and compared to Magnevist, a commercially available
      contrast agent. All the dispersions showed much higher relaxivities compared to
      Magnevist at both low and high magnetic field strengths. Image contrast of the
      nanoassemblies was also found to be much better than Magnevist at the same Gd
      concentration at 11.74 T. Moreover, the Gd-DTPA-MP/PT dispersions showed improved
      relaxivities over the pure Gd-DTPA-MP dispersion at high magnetic fields. These
      stable colloidal nanoassemblies have high potential to be used as combined
      delivery matrices for diagnostics and therapeutics. 

PMID- 25580810
TI  - Rapid RNA strand scission following C2'-hydrogen atom abstraction.
AB  - C2'-Nucleotide radicals have been proposed as key intermediates in direct strand
      break formation in RNA exposed to ionizing radiation. Uridin-2'-yl radical (1)
      was independently generated in single- and double-stranded RNA via photolysis of
      a ketone precursor. Direct stand breaks result from heterolytic cleavage of the
      adjacent C3'-carbon-oxygen bond. Trapping of 1 by O2 or beta-mercaptoethanol (1
      M) does not compete with strand scission, indicating that phosphate elimination
      is >10(6) s(-1). Uracil loss also does not compete with strand scission. When
      considered in conjunction with reports that nucleobase radicals produce 1, this
      chemistry explains why RNA is significantly more susceptible to strand scission
      by ionizing radiation (hydroxyl radical) than is DNA. 

PMID- 25580809
TI  - Sustained effect of simulation-based ultrasound training on clinical performance:
      a randomized trial.
AB  - OBJECTIVE: To study the effect of initial simulation-based transvaginal
      sonography (TVS) training compared with clinical training only, on the clinical
      performance of residents in obstetrics and gynecology (Ob-Gyn), assessed 2 months
      into their residency. METHODS: In a randomized study, new Ob-Gyn residents (n =
      33) with no prior ultrasound experience were recruited from three teaching
      hospitals. Participants were allocated to either simulation-based training
      followed by clinical training (intervention group; n = 18) or clinical training
      only (control group; n = 15). The simulation-based training was performed using a
      virtual-reality TVS simulator until an expert performance level was attained, and
      was followed by training on a pelvic mannequin. After 2 months of clinical
      training, one TVS examination was recorded for assessment of each resident's
      clinical performance (n = 26). Two ultrasound experts blinded to group allocation
      rated the scans using the Objective Structured Assessment of Ultrasound Skills
      (OSAUS) scale. RESULTS: During the 2 months of clinical training, participants in
      the intervention and control groups completed an average +/- SD of 58 +/- 41 and
      63 +/- 47 scans, respectively (P = 0.67). In the subsequent clinical performance
      test, the intervention group achieved higher OSAUS scores than did the control
      group (mean score, 59.1% vs 37.6%, respectively; P < 0.001). A greater proportion
      of the intervention group passed a pre-established pass/fail level than did
      controls (85.7% vs 8.3%, respectively; P < 0.001). CONCLUSION: Simulation-based
      ultrasound training leads to substantial improvement in clinical performance that
      is sustained after 2 months of clinical training. (c) 2015 The Authors.
      Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on
      behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

PMID- 25580811
TI  - Design, synthesis, X-ray crystallographic analysis, and biological evaluation of
      thiazole derivatives as potent and selective inhibitors of human dihydroorotate
      dehydrogenase.
AB  - Human dihydroorotate dehydrogenase (HsDHODH) is a flavin-dependent mitochondrial
      enzyme that has been certified as a potential therapeutic target for the
      treatment of rheumatoid arthritis and other autoimmune diseases. On the basis of
      lead compound 4, which was previously identified as potential HsDHODH inhibitor,
      a novel series of thiazole derivatives were designed and synthesized. The X-ray
      complex structures of the promising analogues 12 and 33 confirmed that these
      inhibitors bind at the putative ubiquinone binding tunnel and guided us to
      explore more potent inhibitors, such as compounds 44, 46, and 47 which showed
      double digit nanomolar activities of 26, 18, and 29 nM, respectively. Moreover,
      44 presented considerable anti-inflammation effect in vivo and significantly
      alleviated foot swelling in a dose-dependent manner, which disclosed that
      thiazole-scaffold analogues can be developed into the drug candidates for the
      treatment of rheumatoid arthritis by suppressing the bioactivity of HsDHODH. 

PMID- 25580813
TI  - Inclusion of fermented foods in food guides around the world.
AB  - Fermented foods have been a well-established part of the human diet for thousands
      of years, without much of an appreciation for, or an understanding of, their
      underlying microbial functionality, until recently. The use of many organisms
      derived from these foods, and their applications in probiotics, have further
      illustrated their impact on gastrointestinal wellbeing and diseases affecting
      other sites in the body. However, despite the many benefits of fermented foods,
      their recommended consumption has not been widely translated to global inclusion
      in food guides. Here, we present the case for such inclusion, and challenge
      health authorities around the world to consider advocating for the many benefits
      of these foods. 

PMID- 25580812
TI  - Placental adaptations in growth restriction.
AB  - The placenta is the primary interface between the fetus and mother and plays an
      important role in maintaining fetal development and growth by facilitating the
      transfer of substrates and participating in modulating the maternal immune
      response to prevent immunological rejection of the conceptus. The major
      substrates required for fetal growth include oxygen, glucose, amino acids and
      fatty acids, and their transport processes depend on morphological
      characteristics of the placenta, such as placental size, morphology, blood flow
      and vascularity. Other factors including insulin-like growth factors, apoptosis,
      autophagy and glucocorticoid exposure also affect placental growth and substrate
      transport capacity. Intrauterine growth restriction (IUGR) is often a consequence
      of insufficiency, and is associated with a high incidence of perinatal morbidity
      and mortality, as well as increased risk of cardiovascular and metabolic diseases
      in later life. Several different experimental methods have been used to induce
      placental insufficiency and IUGR in animal models and a range of factors that
      regulate placental growth and substrate transport capacity have been
      demonstrated. While no model system completely recapitulates human IUGR, these
      animal models allow us to carefully dissect cellular and molecular mechanisms to
      improve our understanding and facilitate development of therapeutic
      interventions. 

PMID- 25580818
TI  - Quest for anionic MOF membranes: continuous sod-ZMOF membrane with CO2 adsorption
      driven selectivity.
AB  - We report the fabrication of the first continuous zeolite-like metal-organic
      framework (ZMOF) thin-film membrane. A pure phase sod-ZMOF, sodalite topology,
      membrane was grown and supported on a porous alumina substrate using a
      solvothermal crystallization method. The absence of pinhole defects in the film
      was confirmed and supported by the occurrence of quantifiable time-lags, for all
      studied gases, during constant volume/variable pressure permeation tests. For
      both pure and mixed gas feeds, the sod-ZMOF-1 membrane exhibits favorable
      permeation selectivity toward carbon dioxide over relevant industrial gases such
      as H2, N2, and CH4, and it is mainly governed by favorable CO2 adsorption. 

PMID- 25580817
TI  - Injury and subsequent regeneration of muscles for activation of local innate
      immunity to facilitate the development and relapse of autoimmune myositis in
      C57BL/6 mice.
AB  - OBJECTIVE: To determine whether injury and regeneration of the skeletal muscles
      induce an inflammatory milieu that facilitates the development and relapse of
      autoimmune myositis. METHODS: The quadriceps of C57BL/6 mice were injured with
      bupivacaine hydrochloride (BPVC) and evaluated histologically. Macrophages and
      regenerating myofibers in the treated muscles and differentiating C2C12 myotubes
      were examined for cytokine expression. Mice were immunized with C protein
      fragments at the base of the tail and in the right hind footpads (day 0) to evoke
      systemic anti-C protein immunity and to induce local myositis in the right hind
      limbs. The contralateral quadriceps muscles were injured with BPVC or phosphate
      buffered saline (PBS) on day 7 or after spontaneous regression of myositis (day
      42). The quadriceps muscle in nonimmunized mice was injured with BPVC on day 7.
      The muscles were examined histologically 14 days after treatment. RESULTS: The
      BPVC-injured muscles had macrophage infiltration most abundantly at 3 days after
      the injection, with emergence of regenerating fibers from day 5. The macrophages
      expressed inflammatory cytokines, including tumor necrosis factor alpha,
      interleukin-1beta, and CCL2. Regenerating myofibers and C2C12 myotubes also
      expressed the cytokines. The BPVC-injected muscles from nonimmunized mice had
      regenerating myofibers with resolved cell infiltration 14 days after treatment.
      In mice preimmunized with C protein fragments, the muscles injected with BPVC on
      day 7 as well as on day 42, but not those injected with PBS, had myositis
      accompanied by CD8+ T cell infiltration. CONCLUSION: Injury and regeneration
      could set up an inflammatory milieu in the muscles and facilitate the development
      and relapse of autoimmune myositis.

PMID- 25580814
TI  - An investigation into the association between DNA damage and dietary fatty acid
      in men with prostate cancer.
AB  - Prostate cancer is a growing problem in New Zealand and worldwide, as populations
      adopt a Western style dietary pattern. In particular, dietary fat is believed to
      be associated with oxidative stress, which in turn may be associated with cancer
      risk and development. In addition, DNA damage is associated with the risk of
      various cancers, and is regarded as an ideal biomarker for the assessment of the
      influence of foods on cancer. In the study presented here, 20 men with prostate
      cancer adhered to a modified Mediterranean style diet for three months. Dietary
      records, blood fatty acid levels, prostate specific antigen, C-reactive protein
      and DNA damage were assessed pre- and post-intervention. DNA damage was inversely
      correlated with dietary adherence (p = 0.013) and whole blood monounsaturated
      fatty acids (p = 0.009) and oleic acid (p = 0.020). DNA damage was positively
      correlated with the intake of dairy products (p = 0.043), red meat (p = 0.007)
      and whole blood omega-6 polyunsaturated fatty acids (p = 0.015). Both the source
      and type of dietary fat changed significantly over the course of the dietary
      intervention. Levels of DNA damage were correlated with various dietary fat
      sources and types of dietary fat. 

PMID- 25580816
TI  - Gold nanorods coated with mesoporous silica shell as drug delivery system for
      remote near infrared light-activated release and potential phototherapy.
AB  - In this study, we report the synthesis of a nanoscaled drug delivery system,
      which is composed of a gold nanorod-like core and a mesoporous silica shell
      (GNR@MSNP) and partially uploaded with phase-changing molecules (1-tetradecanol,
      TD, T(m) 39  degrees C) as gatekeepers, as well as its ability to regulate the
      release of doxorubicin (DOX). Indeed, a nearly zero premature release is
      evidenced at physiological temperature (37  degrees C), whereas the DOX release
      is efficiently achieved at higher temperature not only upon external heating, but
      also via internal heating generated by the GNR core under near infrared
      irradiation. When tagged with folate moieties, GNR@MSNPs target specifically to
      KB cells, which are known to overexpress the folate receptors. Such a precise
      control over drug release, combining with the photothermal effect of GNR cores,
      provides promising opportunity for localized synergistic photothermal ablation
      and chemotherapy. Moreover, the performance in killing the targeted cancer cells
      is more efficient compared with the single phototherapeutic modality of
      GNR@MSNPs. This versatile combination of local heating, phototherapeutics,
      chemotherapeutics and gating components opens up the possibilities for designing
      multifunctional drug delivery systems.

PMID- 25580815
TI  - Guidelines for feeding very low birth weight infants.
AB  - Despite the fact that feeding a very low birth weight (VLBW) neonate is a
      fundamental and inevitable part of its management, this is a field which is beset
      with controversies. Optimal nutrition improves growth and neurological outcomes,
      and reduces the incidence of sepsis and possibly even retinopathy of prematurity.
      There is a great deal of heterogeneity of practice among neonatologists and
      pediatricians regarding feeding VLBW infants. A working group on feeding
      guidelines for VLBW infants was constituted in McMaster University, Canada. The
      group listed a number of important questions that had to be answered with respect
      to feeding VLBW infants, systematically reviewed the literature, critically
      appraised the level of evidence, and generated a comprehensive set of guidelines.
      These guidelines form the basis of this state-of-art review. The review touches
      upon trophic feeding, nutritional feeding, fortification, feeding in special
      circumstances, assessment of feed tolerance, and management of gastric residuals,
      gastro-esophageal reflux, and glycerin enemas. 

PMID- 25580819
TI  - Selective oxidation of alkyl-substituted polyaromatics using ruthenium-ion
      catalyzed oxidation.
AB  - Ruthenium-ion-catalyzed oxidation of a range of alkylated polyaromatics has been
      studied. 2-Ethylnaphthalene was used as a model substrate, and oxidation can be
      performed in either a conventional biphasic or in a monophasic solvent system. In
      either case the reaction rates and product selectivity are identical. The
      reaction products indicate that the aromatic ring system is oxidized in
      preference to the alkyl chain. This analysis is possible due to the development
      of a quantitative NMR protocol to determine the relative amounts of aliphatic and
      aromatic protons. From a systematic set of substrates we show that as the length
      of the alkyl chain substituent on a polyaromatic increases, the proportion of
      products in which the chain remains attached to the aromatic system increases.
      Larger polyaromatic systems, based on pyrene and phenanthrene, show greater
      reactivity than those with fewer aromatic rings, and the alkyl chains are more
      stable to oxidation. 

PMID- 25580821
TI  - Comprehensive evaluation of two genome-scale metabolic network models for
      Scheffersomyces stipitis.
AB  - Genome-scale metabolic network models represent the link between the genotype and
      phenotype of the organism, which are usually reconstructed based on the genome
      sequence annotation and relevant biochemical and physiological information. These
      models provide a holistic view of the organism's metabolism, and constraint-based
      metabolic flux analysis methods have been used extensively to study genome-scale
      cellular metabolic networks. It is clear that the quality of the metabolic
      network model determines the outcome of the application. Therefore, it is
      critically important to determine the accuracy of a genome-scale model in
      describing the cellular metabolism of the modeled strain. However, because of the
      model complexity, which results in a system with very high degree of freedom, a
      good agreement between measured and computed substrate uptake rates and product
      secretion rates is not sufficient to guarantee the predictive capability of the
      model. To address this challenge, in this work we present a novel system
      identification based framework to extract the qualitative biological knowledge
      embedded in the quantitative simulation results from the metabolic network
      models. The extracted knowledge can serve two purposes: model validation during
      model development phase, which is the focus of this work, and knowledge discovery
      once the model is validated. This framework bridges the gap between the large
      amount of numerical results generated from genome-scale models and the knowledge
      that can be easily understood by biologists. The effectiveness of the proposed
      framework is demonstrated by its application to the analysis of two recently
      published genome-scale models of Scheffersomyces stipitis.

PMID- 25580820
TI  - Tunable release of multiplex biochemicals by plasmonically active rotary
      nanomotors.
AB  - It is highly desirable to precisely tune the molecule release rate from the
      surfaces of nanoparticles (NPs) that are relevant to cancer therapy and single
      cell biology. An innovative mechanism is reported to actively tune the
      biochemical release rate by rotation of NPs. Plasmonic nanomotors were assembled
      from NPs and applied in multiplex biochemical release and detection. Both single
      and multiplex biosignals can be released in a tunable fashion by controlling the
      rotation speed of the nanomotors. The chemistry and release rate of individual
      chemicals can be revealed by Raman spectroscopy. The fundamental mechanism was
      modeled quantitatively and attributed to the fluidic boundary-layer reduction
      owing to the liquid convection. This work, which explored the synergistic
      attributes of surface enhanced Raman scattering and nanoelectromechanical
      systems, could inspire new sensors that are potentially interesting for various
      bio-applications. 

PMID- 25580822
TI  - Proteomics of a conundrum: Thoughts on addressing the aetiology versus
      progression of multiple sclerosis.
AB  - Currently in the field of multiple sclerosis (MS) research there is an ongoing
      debate concerning the cause of the disease. MS is widely considered to begin with
      an autoimmune dysregulation. The disease does have a prominent autoimmune
      component however this may be representative of a secondary effect. There is
      growing evidence that the disease may be initiated by an underlying degeneration
      of oligodendrocytes. In our viewpoint, we discuss the potential differences
      between the aetiology and progression of MS. For the most part, proteomic
      analysis has focused on the autoimmune component of the disease. We suggest that
      proteomic analysis should be applied to investigating oligodendrocyte
      degeneration. We discuss the potential of the cuprizone animal model of
      demyelination and its usefulness in understanding oligodendrocyte degeneration.
      Immune suppressive therapies are effective at reducing clinical symptoms and
      improving quality of life. However, a cure is still lacking and as such the
      disease does still progress. We suggest that if the initiating cause is poorly
      understood, then curing MS is unlikely. 

PMID- 25580823
TI  - Pediatric aplastic anemia and refractory cytopenia: A retrospective analysis
      assessing outcomes and histomorphologic predictors.
AB  - Pediatric acquired aplastic anemia (AA) is a bone marrow disorder that is
      difficult to distinguish from inherited bone marrow failure syndromes and
      hypocellular refractory cytopenia of childhood (RCC). Historically, patients with
      hypocellular RCC have been given the diagnosis of AA. To assess the clinical and
      histologic distinction between RCC and AA, we performed a retrospective analysis
      of 149 patients previously diagnosed with AA between 1976 and 2010. We evaluated
      event free survival (EFS), overall survival (OS), response rates to
      immunosuppressive therapy, treatment-related toxicities and clonal evolution. The
      5-year EFS and OS were 50.8% +/- 5.5% and 73.1% +/- 4.7%, respectively. Patients
      with very severe AA had worse OS compared to patients with severe and moderately
      severe AA. Seventy-two patients had diagnostic pathology specimens available for
      review. Three pediatric hematopathologists reviewed and reclassified these
      specimens as AA, RCC or Other based on 2008 WHO Criteria. The concordance between
      pathologists in the diagnosis of AA or RCC was modest. RCC was associated with a
      trend toward improved OS and EFS and was not prognostic of immunosuppression
      therapy treatment failure. There was a low rate of clonal evolution exclusively
      associated with moderately severe AA. Our findings indicate that a diagnosis of
      RCC is difficult to establish with certainty and does not predict outcomes,
      calling into question the reproducibility and clinical significance of the RCC
      classification and warranting further studies.

PMID- 25580825
TI  - Comparison between MRI and CT in prediction of peritoneal carcinomatosis index
      (PCI) in patients undergoing cytoreductive surgery in relation to the experience
      of the radiologist.
AB  - BACKGROUND: To compare CT and MRI for peritoneal carcinomatosis index (PCI)
      assessment and to compare assessments made by the radiologist based on their
      experiences. METHOD AND MATERIALS: MRI and CT of abdomen and pelvis were
      performed on 39 prospectively followed by surgery directly. Two blinded
      radiologists with different experience levels evaluated PCI separately on
      different occasions on 19 cases initially and later on the remaining 20. The
      agreement between the radiologists' assessment and surgical findings in total and
      per site were recorded. RESULTS: Total PCI: The experienced radiologist was able
      to assess total tumor burden correctly on both CT and MRI (kappa = 1.0). For the
      inexperienced radiologist the assessment was better on CT (kappa = 0.73) compared
      to MRI (kappa = 0.58). Different sites: The experienced radiologist showed high
      agreement with kappa = 0.77 for MRI and 0.80 for CT. Corresponding figures were
      0.39 and 0.60 for the inexperienced radiologist. For the second phase the
      agreement levels increased for the inexperienced radiologist increased to 0.80
      and 0.70, respectively. CONCLUSION: CT and MRI are equal when read by experienced
      radiologist. CT shows better results when read by an inexperienced radiologist
      compared to MRI, however the results of the latter can easily be improved.

PMID- 25580826
TI  - An electron acceptor challenging fullerenes for efficient polymer solar cells.
AB  - A novel non-fullerene electron acceptor (ITIC) that overcomes some of the
      shortcomings of fullerene acceptors, for example, weak absorption in the visible
      spectral region and limited energy-level variability, is designed and
      synthesized. Fullerene-free polymer solar cells (PSCs) based on the ITIC acceptor
      are demonstrated to exhibit power conversion efficiencies of up to 6.8%, a record
      for fullerene-free PSCs. 

PMID- 25580824
TI  - Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide-a for early-stage
      cancer of the larynx: Phase Ib study.
AB  - BACKGROUND: The purpose of this study was for us to report results regarding the
      safety of 3-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) mediated photodynamic
      therapy (PDT) in early laryngeal disease, and offer preliminary information on
      treatment responses. METHODS: A single-institution, phase Ib, open label,
      noncomparative study of HPPH-PDT in patients with high-risk dysplasia, carcinoma
      in situ, and T1 squamous cell carcinoma (SCC) of the larynx. The primary outcomes
      were safety and maximum tolerated dose (MTD), and the secondary outcome was
      response. RESULTS: Twenty-nine patients and 30 lesions were treated. The most
      common adverse event (AE) was transient hoarseness of voice. Severe edema,
      requiring tracheostomy, was the most serious AE, which occurred in 2 patients
      within several hours of therapy. The MTD was 100 J/cm(2) . Patients with T1 SCC
      seemed to have good complete response rate (82%) to HPPH-PDT at MTD. CONCLUSION:
      HPPH-PDT can be safely used to treat early-stage laryngeal cancer, with potential
      efficacy. (c) 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc.
      Head Neck 38: E377-E383, 2016.

PMID- 25580827
TI  - An electrochromic painter's palette: color mixing via solution co-processing.
AB  - Electrochromic polymers (ECPs) have been shown to be synthetically tunable,
      producing a full palette of vibrantly colored to highly transmissive polymers.
      The development of these colored-to-transmissive ECPs employed synthetic design
      strategies for broad color targeting; however, due to the subtleties of color
      perception and the intricacies of polymer structure and color relationships, fine
      color control is difficult. In contrast, color mixing is a well-established
      practice in the printing industry. We have identified three colored-to
      transmissive switching electrochromic polymers, referred to as ECP-Cyan (ECP-C),
      ECP-Magenta (ECP-M), and ECP-Yellow (ECP-Y), which, via the co-processing of
      multicomponent ECP mixtures, follow the CMY color mixing model. The presented
      work qualitatively assesses the thin film characteristics of solution co
      processed ECP mixtures. To quantitatively determine the predictability of the
      color properties of ECP mixtures, we estimated mass extinction coefficients
      (epsilonmass) from solution spectra of the CMY ECPs and compared the estimated
      and experimentally observed color values of blends via a calculated color
      difference (DeltaEab). The values of DeltaEab range from 8 to 26 across all
      mixture compositions, with an average value of 15, representing a reasonable
      degree of agreement between predicted and observed color values. We demonstrate
      here the ability to co-process ECP mixtures into vibrantly colored, visually
      continuous films and the ability to estimate the color properties produced in
      these mixed ECP films. 

PMID- 25580828
TI  - The Contribution of Agriculture, Forestry and other Land Use activities to Global
      Warming, 1990-2012.
AB  - We refine the information available through the IPCC AR5 with regard to recent
      trends in global GHG emissions from agriculture, forestry and other land uses
      (AFOLU), including global emission updates to 2012. Using all three available
      AFOLU datasets employed for analysis in the IPCC AR5, rather than just one as
      done in the IPCC AR5 WGIII Summary for Policy Makers, our analyses point to a
      down-revision of global AFOLU shares of total anthropogenic emissions, while
      providing important additional information on subsectoral trends. Our findings
      confirm that the share of AFOLU emissions to the anthropogenic total declined
      over time. They indicate a decadal average of 28.7 +/- 1.5% in the 1990s and 23.6
      +/- 2.1% in the 2000s and an annual value of 21.2 +/- 1.5% in 2010. The IPCC AR5
      had indicated a 24% share in 2010. In contrast to previous decades, when
      emissions from land use (land use, land use change and forestry, including
      deforestation) were significantly larger than those from agriculture (crop and
      livestock production), in 2010 agriculture was the larger component, contributing
      11.2 +/- 0.4% of total GHG emissions, compared to 10.0 +/- 1.2% of the land use
      sector. Deforestation was responsible for only 8% of total anthropogenic
      emissions in 2010, compared to 12% in the 1990s. Since 2010, the last year
      assessed by the IPCC AR5, new FAO estimates indicate that land use emissions have
      remained stable, at about 4.8 Gt CO2 eq yr-1 in 2012. Emissions minus removals
      have also remained stable, at 3.2 Gt CO2 eq yr-1 in 2012. By contrast,
      agriculture emissions have continued to grow, at roughly 1% annually, and
      remained larger than the land use sector, reaching 5.4 Gt CO2 eq yr-1 in 2012.
      These results are useful to further inform the current climate policy debate on
      land use, suggesting that more efforts and resources should be directed to
      further explore options for mitigation in agriculture, much in line with the
      large efforts devoted to REDD+ in the past decade.

PMID- 25580829
TI  - Surfactant free superparamagnetic iron oxide nanoparticles for stable ferrofluids
      in physiological solutions.
AB  - A process is reported to obtain a nanoparticle sol from co-precipitated iron
      oxide particles without using any surfactant. The sol - a true ferrofluid - is
      not only stable over a wide range of pH but also in physiological solutions. This
      is a decisive step towards biomedical applications where nanoparticle
      agglomeration could so far only be prevented by using unwanted surfactants. 

PMID- 25580830
TI  - The influence of a 21 kDa Kunitz-type trypsin inhibitor from nonhost madras
      thorn, Pithecellobium dulce, seeds on H. armigera (Hubner) (Lepidoptera:
      Noctuidae).
AB  - A trypsin inhibitor purified from the seeds of the Manila tamarind,
      Pithecellobium dulce (PDTI), was studied for its effects on growth parameters and
      developmental stages of Helicoverpa armigera. PDTI exhibited inhibitory activity
      against bovine trypsin (~86%; ~1.33 ug/ml IC50). The inhibitory activity of PDTI
      was unaltered over a wide range of temperature, pH, and in the presence of
      dithiothreitol. Larval midgut proteases were unable to digest PDTI for up to 12 h
      of incubation. Dixon and Lineweaver-Burk double reciprocal plots analysis
      revealed a competitive inhibition mechanism and a Ki of ~3.9 * 10(-8) M. Lethal
      dose (0.50% w/w) and dosage for weight reduction by 50% (0.25% w/w) were
      determined. PDTI showed a dose-dependent effect on mean larval weight and a
      series of nutritional disturbances. In artificial diet at 0.25% w/w PDTI, the
      efficiency of conversion of ingested food, of digested food, relative growth
      rate, and growth index declined, whereas approximate digestibility, relative
      consumption rate, metabolic cost, consumption index, and total developmental
      period were increased in larvae. This is the first report of antifeedant and
      antimetabolic activities of PDTI on midgut proteases of H. armigera.

PMID- 25580831
TI  - Characterization of quinoa seed proteome combining different protein
      precipitation techniques: Improvement of knowledge of nonmodel plant proteomics.
AB  - A shotgun proteomics approach was used to characterize the quinoa seed proteome.
      To obtain comprehensive proteomic data from quinoa seeds three different
      precipitation procedures were employed: MeOH/CHCl3 /double-distilled H2 O,
      acetone either alone or with trichloroacetic acid; the isolated proteins were
      then in-solution digested and the resulting peptides were analyzed by nano-liquid
      chromatography coupled to tandem mass spectrometry. However, since quinoa is a
      nonmodel plant species, only a few protein sequences are included in the most
      widely known protein sequence databases. To improve the data reliability a
      UniProt subdatabase, containing only proteins of Caryophillales order, was used.
      A total of 352 proteins were identified and evaluated both from a qualitative and
      quantitative point of view. This combined approach is certainly useful to
      increase the final number of identifications, but no particular class of proteins
      was extracted and identified in spite of the different chemistries and the
      different precipitation protocols. However, with respect to the other two
      procedures, from the relative quantitative analysis, based on the number of
      spectral counts, the trichloroacetic acid/acetone protocol was the best procedure
      for sample handling and quantitative protein extraction. This study could pave
      the way to further high-throughput studies on Chenopodium Quinoa. 

PMID- 25580832
TI  - Using social epidemiology and neuroscience to explore the relationship between
      job stress and frontotemporal cortex activity among workers.
AB  - Mental health problems, such as depression, are increasingly common among
      workers. Job-related stresses, including psychological demands and a lack of
      discretion in controlling one's own work environment, are important causal
      factors. However, the mechanisms through which job-related stress may affect
      brain function remain unknown. We sought to identify the relationship between job
      related stress and frontotemporal cortex activation using near-infrared
      spectroscopy. Seventy-nine (45 females, 34 males) Japanese employees, aged 26-51
      years, were recruited from respondents to the Japanese Study of Stratification,
      Health, Income, and Neighborhood survey. Job-related stress was measured using
      the Japanese version of Job Content Questionnaire, which can index "job demand"
      and "job control". We found a significant correlation between higher "job demand"
      and smaller oxygenated hemoglobin [oxy-Hb] changes in the left dorsolateral
      prefrontal cortex in female (r = -.54 to -.44). Significant correlations between
      higher "job control" and greater [oxy-Hb] changes in the right temporal cortex
      were observed among male, and in the combined sample (r = .46-.64). This initial
      cross-sectional observation suggests that elevated job-related stress is related
      to decrease frontotemporal cortex activation among workers. Integrating social
      epidemiology and neuroscience may be a powerful strategy for understanding how
      individuals' brain functions may mediate between the job-related stress or
      psychosocial work characteristics and public mental health.

PMID- 25580833
TI  - Exploring outcomes and initial self-report of client motivation in a college
      counseling center.
AB  - OBJECTIVE: To explore the association between college counseling center clients'
      initial self-report of motivation and counseling outcome. PARTICIPANTS: The
      sample was composed of 331 student clients who utilized a college counseling
      center from August 2007 to August 2009. The college is a public, mid-size, urban
      university in the Southeast. METHODS: Motivation was measured at intake by a self
      report of change readiness item. A quantitative study that employed a 5-group,
      pretest-posttest design included 331 student participants. Counseling outcome was
      measured using the Outcome Questionnaire 45.2. RESULTS: As assigned by the
      clients' self-report of change readiness, counseling outcome for 5 motivation
      groups differed significantly (p = .004; alpha < .05). Compulsory participation
      in counseling was treated as a possible confound and was not a significant factor
      in counseling outcome (p = .268; alpha < .05). CONCLUSIONS: Participants' initial
      self-report of motivation was significantly associated with counseling outcome.

PMID- 25580834
TI  - In vitro evaluation of the tribological response of Mo-doped graphite-like carbon
      film in different biological media.
AB  - Complicated tribochemical reactions with the surrounding media often occur at the
      prosthesis material, which is a dominant factor causing the premature failure in
      revision surgery. Graphite-like carbon (GLC) film has been proven to be an
      excellent tribological adaption to water-based media, and this work focused on
      the friction and wear behavior of Mo-doped GLC (Mo-GLC)-coated poly(aryl ether
      ether ketone) sliding against Al2O3 counterpart in physiological saline,
      simulated body fluid, and fetal bovine serum (FBS), which mainly emphasized the
      interface interactions of the prosthetic materials/lubricant. Results showed
      different tribological responses of Mo-GLC/Al2O3 pairs strongly correlated with
      the interfacial reactions of the contacting area. Particularly, a transfer layer
      was believed to be responsible for the excellent wear reduction of Mo-GLC/Al2O3
      pair in FBS medium, in which graphitic carbon and protein species were contained.
      The wear mechanisms are tentatively discussed according to the morphologies and
      chemical compositions of the worn surfaces examined by scanning electron
      microscope as well as X-ray photoelectron spectroscopy. 

PMID- 25580835
TI  - Protein maturation and proteolysis in plant plastids, mitochondria, and
      peroxisomes.
AB  - Plastids, mitochondria, and peroxisomes are key organelles with dynamic proteomes
      in photosynthetic eukaryotes. Their biogenesis and activity must be coordinated
      and require intraorganellar protein maturation, degradation, and recycling. The
      three organelles together are predicted to contain ~200 presequence peptidases,
      proteases, aminopeptidases, and specific protease chaperones/adaptors, but the
      substrates and substrate selection mechanisms are poorly understood. Similarly,
      lifetime determinants of organellar proteins, such as N-end degrons and tagging
      systems, have not been identified, but the substrate recognition mechanisms
      likely share similarities between organelles. Novel degradomics tools for
      systematic analysis of protein lifetime and proteolysis could define such
      protease-substrate relationships, degrons, and protein lifetime. Intraorganellar
      proteolysis is complemented by autophagy of whole organelles or selected
      organellar content, as well as by cytosolic protein ubiquitination and
      degradation by the proteasome. This review summarizes (putative) plant organellar
      protease functions and substrate-protease relationships. Examples illustrate key
      proteolytic events. 

PMID- 25580836
TI  - Responses of temperate forest productivity to insect and pathogen disturbances.
AB  - Pest and pathogen disturbances are ubiquitous across forest ecosystems, impacting
      their species composition, structure, and function. Whereas severe abiotic
      disturbances (e.g., clear-cutting and fire) largely reset successional
      trajectories, pest and pathogen disturbances cause diffuse mortality, driving
      forests into nonanalogous system states. Biotic perturbations that disrupt forest
      carbon dynamics either reduce or enhance net primary production (NPP) and carbon
      storage, depending on pathogen type. Relative to defoliators, wood borers and
      invasive pests have the largest negative impact on NPP and the longest recovery
      time. Forest diversity is an important contributing factor to productivity: NPP
      is neutral, marginally enhanced, or reduced in high-diversity stands in which a
      small portion of the canopy is affected (temperate deciduous or mixed forests)
      but very negative in low-diversity stands in which a large portion of the canopy
      is affected (western US forests). Pests and pathogens reduce forest structural
      and functional redundancy, affecting their resilience to future climate change or
      new outbreaks. Therefore, pests and pathogens can be considered biotic forcing
      agents capable of causing consequences of similar magnitude to climate forcing
      factors. 

PMID- 25580837
TI  - Oxygen sensing and signaling.
AB  - Oxygen is an indispensable substrate for many biochemical reactions in plants,
      including energy metabolism (respiration). Despite its importance, plants lack an
      active transport mechanism to distribute oxygen to all cells. Therefore, steep
      oxygen gradients occur within most plant tissues, which can be exacerbated by
      environmental perturbations that further reduce oxygen availability. Plants
      possess various responses to cope with spatial and temporal variations in oxygen
      availability, many of which involve metabolic adaptations to deal with energy
      crises induced by low oxygen. Responses are induced gradually when oxygen
      concentrations decrease and are rapidly reversed upon reoxygenation. A direct
      effect of the oxygen level can be observed in the stability, and thus activity,
      of various transcription factors that control the expression of hypoxia-induced
      genes. Additional signaling pathways are activated by the impact of oxygen
      deficiency on mitochondrial and chloroplast functioning. Here, we describe the
      molecular components of the oxygen-sensing pathway. 

PMID- 25580838
TI  - The plastid terminal oxidase: its elusive function points to multiple
      contributions to plastid physiology.
AB  - Plastids have retained from their cyanobacterial ancestor a fragment of the
      respiratory electron chain comprising an NADPH dehydrogenase and a diiron
      oxidase, which sustain the so-called chlororespiration pathway. Despite its very
      low turnover rates compared with photosynthetic electron flow, knocking out the
      plastid terminal oxidase (PTOX) in plants or microalgae leads to severe
      phenotypes that encompass developmental and growth defects together with
      increased photosensitivity. On the basis of a phylogenetic and structural
      analysis of the enzyme, we discuss its physiological contribution to chloroplast
      metabolism, with an emphasis on its critical function in setting the redox poise
      of the chloroplast stroma in darkness. The emerging picture of PTOX is that of an
      enzyme at the crossroads of a variety of metabolic processes, such as, among
      others, the regulation of cyclic electron transfer and carotenoid biosynthesis,
      which have in common their dependence on the redox state of the plastoquinone
      pool, set largely by the activity of PTOX in darkness. 

PMID- 25580839
TI  - Auditory Verbal Learning Test in a Large Nonclinical Portuguese Population.
AB  - This study aimed to produce adjusted normative data for the Portuguese version of
      the Auditory Verbal Learning Test (AVLT). The study included 1,068 community
      dwelling individuals (736 women, 332 men) aged 18 to 93 years old (Mage = 56
      years, SD = 18) who had educational backgrounds ranging from 0 to 24 years (M =
      9.8 years, SD = 5.3). The results showed that sex, age, and education were
      significantly associated with AVLT performance. These demographic characteristics
      accounted for 24% to 35% of the variance of direct recall trials and for 8% to
      39% of the variance of derived recall scores. The normative data for direct and
      derived recall scores are presented as regression-based algorithms to adjust for
      sex, age, and education with subsequent correspondence between adjusted scores
      and percentile distribution. The norms for the recognition correct score are
      presented as algorithms to estimate the recognition scores for 5th, 10th, and
      18th percentiles for each combination of the variables sex, age, and education.

PMID- 25580840
TI  - Performance of activities of daily living among hospitalized cancer patients.
AB  - BACKGROUND: Many cancer patients report unmet rehabilitation needs.
      Rehabilitation may include activities of daily living (ADL) tasks, but little is
      known about how cancer patients perform these tasks and how they prioritize their
      daily activities. Hence, this study aims to identify and characterize ADL task
      performance problems among a group of adult disabled hospitalized cancer patients
      using interview and questionnaire data. METHODS: Cross-sectional study on
      prevalence of ADL task performance problems experienced by disabled hospitalized
      cancer patients using the Activities of Daily Living Questionnaire (ADL-Q) (n =
      118) and the Canadian Occupational Performance Measure (COPM) (n = 55). RESULTS:
      All 118 patients reported problems with ADL task performance. Based on the ADL-Q
      patients reported more problems within instrumental (I-)ADL than personal (P
      )ADL. In both I-ADL and P-ADL the results differed between women and men. There
      was significant overlap between problems identified using the COPM and the ADL-Q
      instruments. RESULTS from the COPM showed that 65% of problems were related to
      self-care, 25% to leisure, and 19% to productivity. Using both instruments
      identified more ADL problems than when using only one of the instruments.
      CONCLUSION: Adult hospitalized disabled cancer patients experience a high degree
      and variation in difficulties performing ADL, illustrating the need for a
      comprehensively planned assessment of problems and needs.

PMID- 25580841
TI  - Evaluation of hypertension by ambulatory blood pressure monitoring in children
      with solitary kidney.
AB  - In this study, we aimed to investigate the blood pressure (BP) profile in
      children with a unilateral functioning solitary kidney (UFSK). A group of 49
      patients between the ages of 5 and 18 years, and 30 healthy controls between the
      ages of 6 and 16 years were investigated. Gender, weight, height and body mass
      index (BMI) of patients and controls were recorded. BP profile was determined by
      ambulatory BP monitoring (ABPM). We have observed a higher risk of hypertension
      compared with healthy children. Also, masked hypertension is more frequently in
      the patients group and white-coat hypertension was observed in the control group.
      The mean night-time systolic BP (SBP) load (p = 0.01) and 24-h diastolic BP (DBP)
      load (p = 0.008) of children with multicystic dysplastic kidney (MCDK) was
      significantly higher than the healthy group. The mean night-time SBP load (p =
      0.001) of children with unilateral renal agenesis (URA) and 24-h DBP load (p =
      0.003) of children with unilateral atrophic or hypoplastic kidney were
      significantly higher than healthy group. We showed that the children with a
      solitary kidney had increased risk of hypertension. ABPM reflects the BP profile
      more precisely than casual BP measurement and it can be used to evaluate white
      coat and masked hypertension in children with a solitary kidney.

PMID- 25580843
TI  - How health information technology is failing to achieve its full potential.

PMID- 25580842
TI  - A rapid enzymatic assay for high-throughput screening of adenosine-producing
      strains.
AB  - Adenosine is a major local regulator of tissue function and industrially useful
      as precursor for the production of medicinal nucleoside substances. High
      throughput screening of adenosine overproducers is important for industrial
      microorganism breeding. An enzymatic assay of adenosine was developed by combined
      adenosine deaminase (ADA) with indophenol method. The ADA catalyzes the cleavage
      of adenosine to inosine and NH3 , the latter can be accurately determined by
      indophenol method. The assay system was optimized to deliver a good performance
      and could tolerate the addition of inorganic salts and many nutrition components
      to the assay mixtures. Adenosine could be accurately determined by this assay
      using 96-well microplates. Spike and recovery tests showed that this assay can
      accurately and reproducibly determine increases in adenosine in fermentation
      broth without any pretreatment to remove proteins and potentially interfering low
      molecular-weight molecules. This assay was also applied to high-throughput
      screening for high adenosine-producing strains. The high selectivity and accuracy
      of the ADA assay provides rapid and high-throughput analysis of adenosine in
      large numbers of samples. 

PMID- 25580844
TI  - Cerebral microbleeds and early recurrent stroke after transient ischemic attack:
      results from the Korean Transient Ischemic Attack Expression Registry.
AB  - IMPORTANCE: The risk of early recurrent stroke after transient ischemic attack
      (TIA) may be modifiable by optimal treatment. Although ABCD2 scores, diffusion
      weighted imaging lesions, and large artery stenosis are well known to predict
      early stroke recurrence, other neuroimaging parameters, such as cerebral
      microbleeds (CMBs), have not been well explored in patients with TIA. OBJECTIVE:
      To determine the rate of early recurrent stroke after TIA and its neuroimaging
      predictors. DESIGN, SETTING, AND PARTICIPANTS: In this hospital-based,
      multicenter prospective cohort study, consecutive patients with TIA were enrolled
      from 11 university hospitals from July 1, 2010, through December 31, 2012.
      Patients who were admitted within 24 hours after symptom onset and underwent
      diffusion-weighted imaging were included. MAIN OUTCOMES AND MEASURES: The primary
      end point was recurrent stroke within 90 days. Baseline demographics, clinical
      manifestations, neuroimaging findings, and use of antithrombotics or statins also
      were analyzed. RESULTS: A total of 500 patients (mean age, 64 years; male, 291
      [58.2%]; median ABCD2 score, 4) completed 90-day follow-up with guideline-based
      management: antiplatelets (457 [91.4%]), anticoagulants (74 [14.8%]), and statins
      (345 [69.0%]). Recurrent stroke occurred in 25 patients (5.0%). Compared with
      patients without recurrent stroke, those with recurrent stroke were more likely
      to have crescendo TIA (20 [4.2%] vs 4 [16.0%], P = .03), white matter
      hyperintensities (146 [30.7%] vs 13 [52.0%], P = .03), and CMBs (36 [7.6%] vs 7
      [28.0%], P = .003). On multivariable Cox proportional hazards analysis, CMBs
      remained as independent predictors for recurrent stroke (hazard ratio, 3.66; 95%
      CI, 1.47-9.09; P = .005). CONCLUSIONS AND RELEVANCE: Immediate and optimal
      management seems to modify the risk of recurrent stroke after TIA. Cerebral
      microbleeds may be novel predictors of stroke recurrence, which needs further
      validation.

PMID- 25580845
TI  - Renal epithelioid angiomyolipoma in a patient with tuberous sclerosis.

PMID- 25580846
TI  - The clinical success of tooth- and implant-supported zirconia-based fixed dental
      prostheses. A systematic review.
AB  - The aim was to make an inventory of the current literature on the clinical
      performance of tooth- or implant-supported zirconia-based FDPs and analyse and
      discuss any complications. Electronic databases, PubMed.gov, Cochrane Library and
      Science Direct, were searched for original studies reporting on the clinical
      performance of tooth- or implant-supported zirconia-based FDPs. The electronic
      search was complemented by manual searches of the bibliographies of all retrieved
      full-text articles and reviews, as well as a hand search of the following
      journals: International Journal of Prosthodontics, Journal of Oral
      Rehabilitation, International Journal of Oral & Maxillofacial Implants and
      Clinical Oral Implants Research. The search yielded 4253 titles. Sixty-eight
      potentially relevant full-text articles were retrieved. After applying pre
      established criteria, 27 studies were included. Twenty-three studies reported on
      tooth-supported and 4 on implant-supported FDPs. Five of the studies were
      randomised, comparing Y-TZP-based restorations with metal-ceramic or other all
      ceramic restorations. Most tooth-supported FDPs were FDPs of 3-5 units, whereas
      most implant-supported FDPs were full arch. The majority of the studies reported
      on 3- to 5-year follow-up. Life table analysis revealed cumulative 5-year
      survival rates of 93.5% for tooth-supported and 100% for implant-supported FDPs.
      For tooth-supported FDPs, the most common reasons for failure were veneering
      material fractures, framework fractures and caries. Cumulative 5-year
      complication rates were 27.6% and 30.5% for tooth- and implant-supported FDPs,
      respectively. The most common complications were veneering material fractures for
      tooth- as well as implant-supported FDPs. Loss of retention occurred more
      frequently in FDPs luted with zinc phosphate or glass-ionomer cement compared to
      those luted with resin cements. The results suggest that the 5-year survival rate
      is excellent for implant-supported zirconia-based FDPs, despite the incidence of
      complications, and acceptable for tooth-supported zirconia-based FDPs. These
      results are, however, based on a relatively small number of studies, especially
      for the implant-supported FDPs. The vast majority of the studies are not
      controlled clinical trials and have limited follow-up. Thus, interpretation of
      the results should be made with caution. Well-designed studies with large patient
      groups and long follow-up times are needed before general recommendations for the
      use of zirconia-based restorations can be provided.

PMID- 25580847
TI  - Evaluation of synergistic effects of resynchronization therapy and a beta-blocker
      up-titration strategy based on a predefined patient-management program: the
      RESTORE study.
AB  - Prior studies have suggested that a substantial number of eligible heart failure
      (HF) patients fail to receive beta-blocker therapy, or receive it at a suboptimal
      dose. The aim of this study is to assess the benefit of a predefined management
      program designed for beta-blocker up-titration, evaluating the synergistic effect
      of cardiac resynchronization therapy (CRT) and beta-blockers in a HF population.
      The Resynchronization Therapy and beta-Blocker Titration (RESTORE) study is a
      prospective, case-control, multicenter cohort study designed to test the
      hypothesis that a beta-blocker up-titration strategy based on a predefined
      management program maximizes the beneficial effect of CRT, increasing the number
      of patients reaching the target dose of beta-blockers and improving their
      clinical outcome. All study patients receive an implantable defibrillator for CRT
      delivery in accordance with current guidelines. Enrollments started in December
      2011 and are scheduled to end in December 2014. Approximately 250 consecutive
      patients will be prospectively enrolled in 6 Italian centers and followed up for
      24 months after implantation. The primary endpoint is to demonstrate that CRT may
      allow titration of beta-blockers until the optimal dose, or at least to the
      effective dose, in patients with HF. This study might provide important
      information about the benefit of a predefined management program for beta-blocker
      up-titration in patients receiving CRT. Moreover, assessment of health-care
      utilization and the consumption of resources will allow estimating the potential
      utility of remote monitoring by means of an automated telemedicine system in
      facilitating the titration of beta-blockers in comparison with a standard in
      hospital approach. 

PMID- 25580848
TI  - Insights from life history theory for an explicit treatment of trade-offs in
      conservation biology.
AB  - As economic and social contexts become more embedded within biodiversity
      conservation, it becomes obvious that resources are a limiting factor in
      conservation. This recognition is leading conservation scientists and
      practitioners to increasingly frame conservation decisions as trade-offs between
      conflicting societal objectives. However, this framing is all too often done in
      an intuitive way, rather than by addressing trade-offs explicitly. In contrast,
      the concept of trade-off is a keystone in evolutionary biology, where it has been
      investigated extensively. I argue that insights from evolutionary theory can
      provide methodological and theoretical support to evaluating and quantifying
      trade-offs in biodiversity conservation. I reviewed the diverse ways in which
      trade-offs have emerged within the context of conservation and how advances from
      evolutionary theory can help avoid the main pitfalls of an implicit approach.
      When studying both evolutionary trade-offs (e.g., reproduction vs. survival) and
      conservation trade-offs (e.g., biodiversity conservation vs. agriculture), it is
      crucial to correctly identify the limiting resource, hold constant the amount of
      this resource when comparing different scenarios, and choose appropriate metrics
      to quantify the extent to which the objectives have been achieved. Insights from
      studies in evolutionary theory also reveal how an inadequate selection of
      conservation solutions may result from considering suboptimal rather than
      optional solutions when examining whether a trade-off exits between 2 objectives.
      Furthermore, the shape of a trade-off curve (i.e., whether the relationship
      between 2 objectives follows a concave, convex, or linear form) is known to
      affect crucially the definition of optimal solutions in evolutionary biology and
      very likely affects decisions in biodiversity conservation planning too. This
      interface between evolutionary biology and biodiversity conservation can
      therefore provide methodological guidance to support decision makers in the
      difficult task of choosing among conservation solutions.

PMID- 25580849
TI  - Lipid peroxidation is essential for alpha-synuclein-induced cell death.
AB  - Parkinson's disease is the second most common neurodegenerative disease and its
      pathogenesis is closely associated with oxidative stress. Deposition of
      aggregated alpha-synuclein (alpha-Syn) occurs in familial and sporadic forms of
      Parkinson's disease. Here, we studied the effect of oligomeric alpha-Syn on one
      of the major markers of oxidative stress, lipid peroxidation, in primary co
      cultures of neurons and astrocytes. We found that oligomeric but not monomeric
      alpha-Syn significantly increases the rate of production of reactive oxygen
      species, subsequently inducing lipid peroxidation in both neurons and astrocytes.
      Pre-incubation of cells with isotope-reinforced polyunsaturated fatty acids (D
      PUFAs) completely prevented the effect of oligomeric alpha-Syn on lipid
      peroxidation. Inhibition of lipid peroxidation with D-PUFAs further protected
      cells from cell death induced by oligomeric alpha-Syn. Thus, lipid peroxidation
      induced by misfolding of alpha-Syn may play an important role in the cellular
      mechanism of neuronal cell loss in Parkinson's disease. We have found that
      aggregated alpha-synuclein-induced production of reactive oxygen species (ROS)
      that subsequently stimulates lipid peroxidation and cell death in neurons and
      astrocytes. Specific inhibition of lipid peroxidation by incubation with
      reinforced polyunsaturated fatty acids (D-PUFAs) completely prevented the effect
      of alpha-synuclein on lipid peroxidation and cell death. 

PMID- 25580851
TI  - Use of a web-based education program improves nurses' knowledge of breastfeeding.
AB  - OBJECTIVE: To evaluate the baseline knowledge and knowledge gained of nurses,
      nursing students, midwives, and nurse practitioners who completed Breastfeeding
      Basics, an online educational program. DESIGN: This study reports on an anonymous
      evaluation of an online breastfeeding education program developed and maintained
      to promote evidence-based breastfeeding practice. PARTICIPANTS: Included in the
      study were 3736 nurses, 728 nurse practitioners/midwives, and 3106 nursing
      students from the United States who completed >= one pretest or posttest on the
      Breastfeeding Basics website between April 1999 and December 31, 2011. METHODS:
      Baseline scores were analyzed to determine if nurses' baseline knowledge varied
      by selected demographic variables such as age, gender, professional level,
      personal or partner breastfeeding experience, and whether they were required to
      complete the website for a job or school requirement and to determine knowledge
      gaps. Pretest and posttest scores on all modules and in specific questions with
      low pretest scores were compared as a measure of knowledge gained. RESULTS: Lower
      median pretest scores were found in student nurses (71%), males (71%), those
      required to take the course (75%), and those without personal breastfeeding
      experience (72%). The modules with the lowest median pretest scores were
      Anatomy/Physiology (67%), Growth and Development of the Breastfed Infant (67%),
      the Breastfeeding Couple (73%), and the Term Infant with Problems (60%). Posttest
      scores in all modules increased significantly (p < .001). CONCLUSION:
      Breastfeeding Basics was used by a large number of nurses and nursing students.
      Gaps exist in nurses' breastfeeding knowledge. Knowledge improved in all areas
      based on comparison of pretest and posttest scores.

PMID- 25580850
TI  - Rigosertib induces cell death of a myelodysplastic syndrome-derived cell line by
      DNA damage-induced G2/M arrest.
AB  - A multi-kinase inhibitor, rigosertib (ON 01910.Na) has recently been highlighted
      as a novel type of anti-cancer agent for the treatment of the myelodysplastic
      syndromes (MDS), but its action mechanisms remain to be clarified. We
      investigated the in vitro effects of rigosertib on an MDS-derived cell line MDS-L
      and a myeloid leukemia cell line HL-60. Rigosertib suppressed the proliferation
      of both HL-60 and MDS-L cells and induced apoptosis by inhibition of the PI3
      kinase/Akt pathway. As the effects on cell cycle, rigosertib treatment promoted
      the phosphorylation of histone H2AX and led to the DNA damage-induced G2/M
      arrest. In addition, an immunofluorescence staining study demonstrated the
      abnormal localization of aurora A kinase, suggesting that rigosertib causes
      perturbation of spindle assembly and deregulated mitotic patterns towards cell
      cycle arrest and apoptosis. We also found that rigosertib exerted growth
      inhibitory effects on two lymphoid cell lines, Jurkat and Ramos. We further
      examined the molecular pathways influenced by rigosertib from the gene expression
      profiling data of MDS-L cells and found a possible involvement of rigosertib
      treatment in the upregulation of the genes related to microtubule kinetics and
      the downregulation of the mRNA degradation system. The gene set enrichment
      analysis showed the suppression of "nonsense-mediated mRNA decay (NMD)" as the
      most significantly affected gene set. These data provide a new aspect and a
      potential utility of rigosertib for the treatment of refractory hematopoietic
      malignancies.

PMID- 25580852
TI  - Deep sequencing of the olfactory epithelium reveals specific chemosensory
      receptors are expressed at sexual maturity in the European eel Anguilla anguilla.
AB  - Vertebrate genomes encode a diversity of G protein-coupled receptor (GPCR) that
      belong to large gene families and are used by olfactory systems to detect
      chemical cues found in the environment. It is not clear however, if individual
      receptors from these large gene families have evolved roles that are specific to
      certain life stages. Here, we used deep sequencing to identify differentially
      expressed receptor transcripts in the olfactory epithelia (OE) of freshwater,
      seawater and sexually mature male eels (Anguilla anguilla). This species is
      particularly intriguing because of its complex life cycle, extreme long-distance
      migrations and early-branching position within the teleost phylogeny. In the A.
      anguillaOE, we identified full-length transcripts for 13, 112, 6 and 38 trace
      amine-associated receptors, odorant receptors (OR) and type I and type II
      vomeronasal receptors (V1R and V2R). Most of these receptors were expressed at
      similar levels at different life stages and a subset of OR and V2R-like
      transcripts was more abundant in sexually mature males suggesting that ORs and
      V2R-like genes are important for reproduction. We also identified a set of GPCR
      signal transduction genes that were differentially expressed indicating that eels
      make use of different GPCR signal transduction genes at different life stages.
      The finding that a diversity of chemosensory receptors is expressed in the
      olfactory epithelium and that a subset is differentially expressed suggests that
      most receptors belonging to large chemosensory gene families have functions that
      are important at multiple life stages, while a subset has evolved specific
      functions at different life stages. 

PMID- 25580853
TI  - A proton relay enhances H2O2 sensitivity of GAPDH to facilitate metabolic
      adaptation.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is sensitive to reversible
      oxidative inactivation by hydrogen peroxide (H2O2). Here we show that H2O2
      reactivity of the active site thiolate (C152) is catalyzed by a previously
      unrecognized mechanism based on a dedicated proton relay promoting leaving group
      departure. Disruption of the peroxidatic reaction mechanism does not affect the
      glycolytic activity of GAPDH. Therefore, specific and separate mechanisms mediate
      the reactivity of the same thiolate nucleophile toward H2O2 and glyceraldehyde 3
      phosphate, respectively. The generation of mutants in which the glycolytic and
      peroxidatic activities of GAPDH are comprehensively uncoupled allowed for a
      direct assessment of the physiological relevance of GAPDH H2O2 sensitivity. Using
      yeast strains in which wild-type GAPDH was replaced with H2O2-insensitive mutants
      retaining full glycolytic activity, we demonstrate that H2O2 sensitivity of GAPDH
      is a key component of the cellular adaptive response to increased H2O2 levels. 

PMID- 25580855
TI  - Membrane enzymes: transformers at the interface.

PMID- 25580854
TI  - Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12
      interplay.
AB  - Lysophosphatidylserines (lyso-PSs) are a class of signaling lipids that regulate
      immunological and neurological processes. The metabolism of lyso-PSs remains
      poorly understood in vivo. Recently, we determined that ABHD12 is a major brain
      lyso-PS lipase, implicating lyso-PSs in the neurological disease polyneuropathy,
      hearing loss, ataxia, retinitis pigmentosa and cataract (PHARC), which is caused
      by null mutations in the ABHD12 gene. Here, we couple activity-based profiling
      with pharmacological and genetic methods to annotate the poorly characterized
      enzyme ABHD16A as a phosphatidylserine (PS) lipase that generates lyso-PS in
      mammalian systems. We describe a small-molecule inhibitor of ABHD16A that
      depletes lyso-PSs from cells, including lymphoblasts derived from subjects with
      PHARC. In mouse macrophages, disruption of ABHD12 and ABHD16A respectively
      increases and decreases both lyso-PSs and lipopolysaccharide-induced cytokine
      production. Finally, Abhd16a(-/-) mice have decreased brain lyso-PSs, which runs
      counter to the elevation in lyso-PS in Abhd12(-/-) mice. Our findings illuminate
      an ABHD16A-ABHD12 axis that dynamically regulates lyso-PS metabolism in vivo,
      designating these enzymes as potential targets for treating neuroimmunological
      disorders. 

PMID- 25580856
TI  - Decreased presence of Langerhans cells is a critical determinant for Indian Post
      kala-azar dermal leishmaniasis.
AB  - Post kala-azar dermal leishmaniasis (PKDL) is the dermal sequel of visceral
      leishmaniasis (VL) and occurs after apparent cure or alongside with VL. It is
      confined to South Asia (India, Nepal and Bangladesh) and East Africa (mainly
      Sudan), the incidence being 5-10% and 50-60% respectively. In South Asia, as the
      transmission of VL is anthroponotic, PKDL patients are the proposed disease
      reservoir, thus assuming epidemiological significance, its eradication being
      linked to the control of leishmaniasis. In the absence of an animal model and its
      low incidence, factors contributing towards the immunopathogenesis of PKDL remain
      an open-ended, yet pertinent question. This study delineated the lesional
      immunopathology in terms of granuloma formation, Langerhans cells, tissue
      macrophages along with mRNA expression of IL-12p40 and IL-10. Our study in Indian
      PKDL for the first time identified that the number of CD1a(+) /CD207(+)
      Langerhans cells are decreased and CD68(+) macrophages are increased along with
      the absence of an epitheloid granuloma. Importantly, this decrease in Langerhans
      cells was associated with decreased mRNA expression of IL-12p40 and increased IL
      10. This was reverted with treatment allowing for elimination of parasites and
      disease resolution along with an increase in Langerhans cells and decrease in
      macrophages. Thus, in Indian PKDL, absence of a granuloma formation along with a
      decrease in Langerhans cells collectively caused immune inactivation essential
      for parasite persistence and disease sustenance. 

PMID- 25580857
TI  - Hidden topological order and its correlation with glass-forming ability in
      metallic glasses.
AB  - Unlike the well-defined long-range periodic order that characterizes crystals, so
      far the inherent atomic packing mode in glassy solids remains mysterious. Based
      on molecular dynamics simulations, here we find medium-range atomic packing
      orders in metallic glasses, which are hidden in the diffraction data in terms of
      structure factors or pair correlation functions. The analysis of the hidden
      orders in various metallic glasses indicates that the glassy and crystalline
      solids share a nontrivial structural homology in short-to-medium range, and the
      hidden orders are formulated by inheriting partial crystalline orders during
      glass formation. As the number of chemical components increases, more hidden
      orders are often developed in a metallic glass and entangled topologically. We
      use this phenomenon to explain the geometric frustration in glass formation and
      the glass-forming ability of metallic alloys. 

PMID- 25580858
TI  - Impact of regular exercise on classical brown adipose tissue.

PMID- 25580859
TI  - Multicenter prospective study to optimize the efficacy of triple therapy with
      telaprevir in patients with genotype 1b hepatitis C virus infection according to
      an algorithm based on the drug Adherence, IL-28B Gene Allele and Viral Response
      Trial (AG & RGT).
AB  - AIM: To optimize the therapeutic efficacy of NS3/4A protease inhibitors, a
      multicenter prospective study was performed according to an algorithm based on
      the Adherence, IL-28B Gene Allele and Viral Response Trial (AG & RGT). METHODS: A
      total of 340 patients with genotype 1b hepatitis C virus (HCV) showing serum RNA
      levels of >5 log were enrolled. The duration of ribavirin/pegylated interferon
      (PEG IFN)-alpha-2b therapy was prolonged to 48 weeks in patients with unfavorable
      IL28B alleles showing adherence rates of less than 80% for either drug during the
      first 12 weeks even if RVR had been achieved, and in those in whom cEVR, but not
      RVR, was achieved; furthermore, to 72 weeks in those showing partial early viral
      response. RESULTS: The therapeutic outcomes were assessed in 282 patients, and
      the therapy was set to complete at 24 weeks in 181 patients (64%) and to prolong
      to 48 weeks or 72 weeks in 71 patients (25%). The former group showed a SVR rate
      of 84%, while the latter group showed an SVR rate of 69% with a relapse rate of
      7%. The SVR rate was 33% in the 30 patients (11%) in whom the therapy had to be
      discontinued in less than 12 weeks. Thus, the results of intention-to-treat
      analysis revealed an overall SVR rate of 75%. Multivariate analysis identified
      prolongation of the duration of therapy as a significant factor associated with
      SVR. CONCLUSION: Triple therapy yielded a high SVR rate in the AG & RGT trial via
      attenuation of viral relapse by prolonged ribavirin/PEG IFN-alpha-2b
      administration. (c) 2015 The Japan Society of Hepatology.

PMID- 25580860
TI  - Acute irritant bullous contact dermatitis caused by Euphorbia helioscopia.

PMID- 25580861
TI  - Recurrence of status epilepticus: prognostic role and outcome predictors.
AB  - OBJECTIVE: Predictors of morbidity and mortality after status epilepticus (SE)
      have been studied extensively in hospital- and population-based cohorts. However,
      little attention has been directed toward SE recurrence after an incident
      episode. We investigated clinical and demographic characteristics of patients
      presenting SE recurrence and its specific prognostic role. METHODS: In this
      observational cohort study, we screened our prospective registry of consecutive
      adults with SE between April 2006 and February 2014. Demographic and clinical
      data were compared between incident and recurrent SE episodes; risk of SE
      recurrence was assessed through survival analysis, and the prognostic role of SE
      recurrence with multivariable logistic regressions. RESULTS: Of the incident
      cohort (509 patients), 68 (13%) experienced recurrent SE. The cumulative
      recurrence rate over 4 years was 32%. Recurrence risk was significantly reduced
      after an acute SE etiology (hazard ratio [HR] 0.5, 95% confidence interval [CI]
      0.31-0.82; p = 0.005), and was borderline increased in women (HR 1.59, 95% CI
      0.97-2.65; p = 0.06). Although recurrent SE episodes showed lower morbidity and
      mortality, prognosis was independently related to Status Epilepticus Severity
      Score (STESS) and potentially fatal etiology, but not to SE recurrence.
      SIGNIFICANCE: This study provides class III evidence that SE recurrence involves
      a significant proportion of patients, and that recurrence risk is independently
      associated with chronic etiology and to a lesser extent with female gender.
      However, contrary to underlying cause and SE severity, SE recurrence per se does
      not independently correlate with outcome. Early identification of patients at
      higher risk of SE recurrence may influence their management during follow-up.

PMID- 25580862
TI  - In vivo adverse effects of alpha-tocopherol on the semen quality of male bucks.
AB  - Oxidative stress has detrimental effects on semen quality during spermatogenesis
      and semen processing for artificial insemination. This work was conducted to
      study the effect of different levels of vitamin E on the semen traits, oxidative
      status and trace minerals in Beetal bucks. Thirty-six bucks of similar body
      weight and age (1 year) were randomly divided into four groups. One group was
      kept as control with no supplementation (group 1), and the others were
      supplemented with 200 (group 2), 400 (group 3) and 800 IU (group 4) vitamin
      E/animal/day for 2 months. At the end of the experiment, semen samples were
      collected and evaluated. Seminal plasma was separated to study the concentration
      of superoxide dismutase (SOD), glutathione peroxidase (GPx), aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and trace minerals (Zn,
      Cu, Mn and Fe). Group 3 showed significantly higher (p < 0.05) semen volume and
      per cent motility and lower dead sperm percentage compared to control group.
      Superoxide dismutase, GPx, Zn, Cu and Mn were higher in the same group. The level
      of AST decreased in group 3 without any change on the concentration of ALT. It is
      suggested that vitamin E at the rate of 400 IU/buck/day supported higher semen
      volume, per cent motility, per cent live spermatozoa, antioxidants (SOD, GPx) and
      trace mineral levels (Zn, Cu, Mn) in the seminal plasma. The increased
      supplementation from 0 to 400 showed a general increasing trend in improving
      semen quality. However, the dose of 800 IU/kg had no useful effect in further
      improving the semen quality. 

PMID- 25580863
TI  - Urinary bladder xanthoma: a multi-institutional series of 17 cases.
AB  - AIMS: To present a series of urinary bladder xanthomas and characterize their
      clinical features and associated pathology. METHODS AND RESULTS: We retrieved the
      clinicopathological data of bladder xanthomas, with and without associated
      urothelial neoplasms. We identified six isolated bladder xanthomas and 11 arising
      within or adjacent to urothelial neoplasms. The biopsies showed lamina propria
      aggregates of foamy histiocytes, without an accompanying inflammation. Patients
      presented either incidentally or with microscopic haematuria or irritative
      symptoms. Patients with isolated xanthomas had a mean age of 65.3 years (range:
      54-75 years) and an equal male to female ratio. Four of five patients with
      isolated xanthomas with available serum results had an abnormal lipid profile.
      Eleven patients had xanthomas associated with urothelial neoplasms [papilloma n =
      4, papillary urothelial neoplasm of low malignant potential (PUNLMP) n = 2 and
      low-grade urothelial carcinoma n = 5]. Mean patient age was 62.5 years (range: 51
      69 years) and all were male. Of the six patients with metabolic abnormalities,
      five had hypercholesterolaemia and one had a history of diabetes mellitus.
      CONCLUSION: Bladder xanthomas are rare lesions found in older patients who
      present either non-specifically or with microscopic haematuria or irritative
      symptoms. These lesions are often associated with underlying lipid abnormalities.
      A biopsy is recommended for an accurate diagnosis and to exclude neoplasia.

PMID- 25580864
TI  - Characterization of gene mutations and phenotypes of cystic fibrosis in Chinese
      patients.
AB  - BACKGROUND AND OBJECTIVE: Cystic fibrosis (CF) is a relatively common autosomal
      recessive disorder in Caucasians. CF is considered a very rare disease in Asians,
      and fewer than 30 Chinese CF patients are reported in the literature. We enrolled
      seven patients of Chinese Han origin diagnosed with CF at the Peking Union
      Medical College Hospital, to characterize gene mutations and phenotypes of CF in
      Chinese patients. METHODS: We analysed the clinical presentation and screened the
      coding region of the CFTR gene for each patient. RESULTS: Patients were 0-6 years
      old at onset of symptoms and were 10-28 years old at the time of diagnosis with
      CF. None of the seven patients had a family history of CF, and only one patient
      had parents who were consanguineous. Two patients had gastrointestinal symptoms
      but stool Sudan III results were normal. Four of the seven CF patients also had
      allergic bronchopulmonary aspergillosis. The concentration of chloride in
      patients' sweat ranged from 66 mmol/l to 154 mmol/l. In total, we identified 11
      different mutations in seven CF patients, including one novel mutation (?E7-E11).
      Only one of these mutations (R553X) is present in the Caucasian CFTR common
      mutation-screening panel; and none of the 11 mutations are common in Caucasian CF
      patients. CONCLUSIONS: CF in China is difficult to diagnose because of a
      combination of low awareness, atypical clinical symptoms, and a lack of sweat and
      genetic testing facilities in most hospitals. The mutations identified in Chinese
      CF patients are different from the common Caucasian gene mutations.

PMID- 25580865
TI  - Are major repeater patients addicted to suicidal behavior?
AB  - The literature provides support for the hypothesis that some major repeaters
      (individuals with >=5 lifetime suicide attempts) are addicted to suicidal
      behavior (SB). This study explores whether major repeaters are addicted to SB or
      not using 7 criteria: tolerance (Criterion 1), withdrawal (Criterion 2), loss of
      control (Criterion 3), problems in quitting/cutting down (Criterion 4), much time
      spent using (Criterion 5), substantial reduction in activities (Criterion 6), and
      adverse physiological/physical consequences (Criterion 7). Total dependence on SB
      was indicated by the presence of 3 or more of the 7 criteria in the last 12
      months. This cross-sectional study at Puerta de Hierro University Hospital
      (Madrid, Spain) recruited 118 suicide attempters including 8 major repeaters (7%,
      8/118), who were all females. The association between each SB addiction
      criterion, physiological dependence and total dependence with major repeater
      status was tested for significance and for effect size with odds ratios (ORs) and
      their 95% confidence intervals. As hypothesized, major repeaters met
      significantly higher frequency of criteria for total dependence on SB, OR=62.9
      (6.4-615). A backward stepwise logistic regression model was used to provide an
      OR between major repeater status and total dependence status corrected by
      confounding variables. Age, panic disorder without agoraphobia, borderline
      personality disorder, history of psychiatric inpatient admission, and total
      dependence on SB were introduced as independent variables with major repeater
      status as the dependent variable. The model selected total dependence and age as
      the remaining significant variables in the last step. Accordingly, major
      repeaters appear to be addicted to SB. 

PMID- 25580866
TI  - Teaching medical students in emergency departments: time to reinvent a core
      activity.

PMID- 25580867
TI  - Quantification of fibrosis by collagen proportionate area predicts hepatic
      decompensation in hepatitis C cirrhosis.
AB  - BACKGROUND: It is unclear whether the course of cirrhosis and its prognosis are
      related to the amount of collagen in the liver. AIM: To determine whether
      fibrosis, assessed by collagen proportionate area (CPA) in patients with
      compensated cirrhosis, is associated with the presence of oesophageal varices,
      and predict disease decompensation during the follow-up period. METHODS: We
      prospectively evaluated 118 consecutive patients with compensated cirrhosis to
      correlate fibrosis, assessed by CPA in liver biopsies, with the presence of
      oesophageal varices (OV) and with the rate of liver decompensation (LD)
      development during a median follow-up of 72 months. RESULTS: At baseline 38
      (32.2%) patients had OV and during the follow-up (median 72 months, IQR 47-91),
      17 patients (14.4%) developed LD. The mean CPA value was different in patients
      with and without OV (14.8 +/- 5.9% vs. 21.6 +/- 9.5%, P < 0.001). The best CPA
      cut-off for OV by area under the receiver operating characteristic (AUROC) was
      >=14% and with multivariate logistic analysis CPA was the only variable
      associated with OV (OR: 28.32, 95% CI: 6.30-127.28; P < 0.001). By AUROC analysis
      the best CPA cut-off to predict LD was 18.0%. By Cox regression multivariate
      analysis CPA >=18% (HR: 3.99, 95% CI: 1.04-11.45; P = 0.036), albumin (HR: 0.12,
      95% CI: 0.04-0.43; P = 0.001) and presence of OV (HR: 8.15, 95% CI: 2.31-28.78; P
      = 0.001) were independently associated with LD. CONCLUSION: Quantification of
      fibrosis by collagen proportionate area allows identification of patients with
      compensated HCV cirrhosis with a higher likelihood of clinically relevant portal
      hypertension and a higher risk of decompensation.

PMID- 25580868
TI  - One-Pot Synthesis of Cu2 O/ZnO Nanoparticles at Present of Folic Acid to Improve
      UV-Protective Effect of Cotton Fabrics.
AB  - In this study, the effect of using folic acid on the in situ synthesis process of
      nanostructures has been investigated. Folic acid, as a biotemplate for synthesis
      of Cu2 O/ZnO, was used to improve the reducing and stabilizing the ability of
      cotton fabric and avoid agglomeration of the particles. Scanning electron
      microscopy images revealed that using folic acid caused the formation of
      particles with smaller sizes on the cotton fabric and X-ray diffraction confirmed
      the same crystalline pattern of nanoparticles in comparison with the previous
      synthesis process. The effect of using this biotemplate on different properties
      of treated fabrics including UV-protection effect, hydrophilicity, crease
      recovery angle, softness, thickness and mechanical properties has been evaluated.
      The folic acid had a great influence on UV-protection effect, in synthesis
      procedure, decreasing the droplet absorption time, bending length and improving
      the wrinkle resistance and mechanical properties. Interestingly, the higher
      tensile strength of the treated cotton fabrics proved the incorporation of
      nanoparticles into the cotton fibers. An in situ, green and rapid method can be
      provided by using folic acid for the synthesis of the nanostructures with
      controlled size. 

PMID- 25580869
TI  - Modest blood pressure reduction with valsartan in acute ischemic stroke: a
      prospective, randomized, open-label, blinded-end-point trial.
AB  - BACKGROUND AND AIMS: To assess the efficacy and safety of modest blood pressure
      (BP) reduction with valsartan within 48 h after symptom onset in patients with
      acute ischemic stroke and high BP. METHODS: This was a multicenter, prospective,
      randomized, open-label, blinded-end-point trial. A total of 393 subjects were
      recruited at 28 centers and then randomly assigned in a 1:1 ratio to receive
      valsartan (n = 195) or no treatment (n = 198) for seven-days after presentation.
      The primary outcome was death or dependency, defined as a score of 3-6 on the
      modified Rankin Scale (mRS) at 90 days after symptom onset. Early neurological
      deterioration (END) within seven-days and 90-day major vascular events were also
      assessed. RESULTS: There were 372 patients who completed the 90-day follow-up.
      The valsartan group had 46 of 187 patients (24.6%) with a 90-day mRS 3-6,
      compared with 42 of 185 patients (22.6%) in the control group (odds ratio [OR],
      1.11; 95% confidence interval [CI], 0.69-1.79; P = 0.667). The rate of major
      vascular events did not differ between groups (OR, 1.41; 95% CI, 0.44-4.49; P =
      0.771). There was a significant increase of END in the valsartan group (OR, 2.43;
      95% CI, 1.25-4.73; P = 0.008). CONCLUSIONS: Early reduction of BP with valsartan
      did not reduce death or dependency and major vascular events at 90 days, but
      increased the risk of END.

PMID- 25580870
TI  - Volatile anesthetics for status asthmaticus in pediatric patients: a
      comprehensive review and case series.
AB  - Status asthmaticus is an acute, intractable asthma attack refractory to standard
      interventions that can lead to progressive respiratory failure. Successful
      management requires a fundamental understanding of the disease process, its
      clinical presentation, and proper evaluation. Treatment must be instituted early
      and is aimed at reversing the airway inflammation, bronchoconstriction, and hyper
      reactivity that often lead to lower airway obstruction, impaired ventilation, and
      oxygenation. Most patients are effectively treated with standard therapy
      including beta2-adrenergic agonists and corticosteroids. Others necessitate
      adjunctive therapies and escalation to noninvasive ventilation or intubation. We
      will review the pathophysiology, evaluation, and treatment options for pediatric
      patients presenting with status asthmaticus with a particular focus on refractory
      status asthmaticus treated with volatile anesthetics. In addition, we include a
      proven approach to the management of these patients in the critical care setting,
      which requires close coordination between critical care and anesthesia providers.
      We present a case series of three patients, two of which have the longest
      reported cases of continuous isoflurane use in status asthmaticus. This series
      was obtained from a retrospective chart review and highlights the efficacy of the
      volatile anesthetic, isoflurane, in three pediatric patients with refractory life
      threatening status asthmaticus. 

PMID- 25580871
TI  - Phosphorylation-dependent ubiquitination of paraxial protocadherin (PAPC)
      controls gastrulation cell movements.
AB  - Paraxial protocadherin (PAPC) has been shown to be involved in gastrulation cell
      movements during early embryogenesis. It is first expressed in the dorsal
      marginal zone at the early gastrula stage and subsequently restricted to the
      paraxial mesoderm in Xenopus and zebrafish. Using Xenopus embryos, we found that
      PAPC is also regulated at the protein level and is degraded and excluded from the
      plasma membrane in the axial mesoderm by the late gastrula stage. Regulation of
      PAPC requires poly-ubiquitination that is dependent on phosphorylation. PAPC is
      phosphorylated by GKS3 in the evolutionarily conserved cytoplasmic domain, and
      this in turn is necessary for poly-ubiquitination by an E3 ubiquitin ligase beta
      TrCP. We also show that precise control of PAPC by phosphorylation/ubiquitination
      is essential for normal Xenopus gastrulation cell movements. Taken together, our
      findings unveil a novel mechanism of regulation of a cell adhesion protein and
      show that this system plays a crucial role in vertebrate embryogenesis. 

PMID- 25580873
TI  - Invading slugs (Arion vulgaris) can be vectors for Listeria monocytogenes.
AB  - AIMS: Listeriosis is a frequent silage-associated disease in ruminants. The slugs
      Arion vulgaris are invaders in gardens, vegetable crops and meadows for silage
      production. Field and laboratory studies were conducted to clarify whether slugs
      could host Listeria monocytogenes and thereby constitute a threat to animal feed
      safety. METHODS AND RESULTS: Selective culture of L. monocytogenes from 79 pooled
      slug samples (710 slugs) resulted in 43% positive, 16% with mean L. monocytogenes
      values of 405 CFU g(-1) slug tissues. Of 62 individual slugs cultured, 11% also
      tested positive from surface/mucus. Multilocus sequence typing analysis of 36
      isolates from different slug pools identified 20 sequence types belonging to L.
      monocytogenes lineages I and II. Slugs fed ?4.0 * 10(5)  CFUL. monocytogenes,
      excreted viable L. monocytogenes in faeces for up to 22 days. Excretion of L.
      monocytogenes decreased with time, although there were indications of a short
      enrichment period during the first 24 h. CONCLUSIONS: Arion vulgaris may act as a
      vector for L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: Highly slug
      contaminated grass silage may pose a potential threat to animal feed safety.

PMID- 25580874
TI  - Outreach training model for accredited colorectal specialists in laparoscopic
      colorectal surgery: feasibility and evaluation of challenges.
AB  - AIM: The aim of this study was to explore the feasibility and safety of an
      outreach model of laparoscopic colorectal training of accredited specialists in
      advanced laparoscopic techniques and to explore the challenges of this model from
      the perspective of a National Training Programme (NTP) trainer. METHOD:
      Prospective data were collected for unselected laparoscopic colorectal training
      procedures performed by five laparoscopic colorectal NTP trainees supervised by a
      single NTP trainer with an outreach model between 2009 and 2012. The operative
      and postoperative outcomes were compared with standard laparoscopic colorectal
      training procedures performed by six senior colorectal trainees under the
      supervision of the same NTP trainer within the same study period. The primary
      outcome was 30-day mortality. The Mann-Whitney test was used to compare
      continuous variables and the Chi squared or Fisher's exact tests were applied for
      the analysis of categorical variables. The level of statistical significance was
      set at P < 0.05. RESULTS: During the study period 179 elective laparoscopic
      colorectal procedures were performed. This included 54 cases performed by NTP
      trainees and 125 cases performed by the supervised trainees. There were no
      significant differences in age, gender, body mass index, American Society of
      Anesthesiologists grade, pathology and procedure type between both groups.
      Seventy-eight per cent of the patients operated on by the NTP trainees had had no
      previous abdominal surgery, compared with 50% in the supervised trainees' group
      (P = 0.0005). There were no significant differences in 30-day mortality or the
      operative and postoperative outcome between both groups. There were, however,
      difficulties in training an already established consultant in his or her own
      hospital and these were overcome by certain adjustments to the programme.
      CONCLUSION: Outreach laparoscopic training of colorectal surgeons is a feasible
      and safe model of training accredited specialists and does not compromise patient
      care. The challenges encountered can be overcome with optimum training and
      preparation.

PMID- 25580872
TI  - Regulation of Streptococcus mutans PTS Bio by the transcriptional repressor NigR.
AB  - Streptococcus mutans is implicated in human dental caries, and the carbohydrate
      metabolism of this organism plays an important role in the formation of this
      disease. Carbohydrate transport and metabolism are essential for the survival of
      S. mutans in the oral cavity. It is known that a unique phosphoenolpyruvate-sugar
      phosphotransferase system PTS(B) (io) of S. mutans UA159 is expressed in sucrose
      grown biofilms (Mol Oral Microbiol 28: 2013; 114). In this study we analyzed the
      transcriptional regulation of the operon (O(B) (io) ) encoding the PTS(B) (io)
      and showed that it was repressed by NigR, a LacI-like transcriptional regulator.
      Using electro-mobility shift assay, we described two operators to which NigR
      bound with different affinities. We also identified the transcriptional start
      site and showed that one of the operators overlaps with the promoter and
      presumably represses initiation of transcription. Mutational analyses revealed
      the key nucleotides in the operators required for high-affinity binding of NigR.
      PTS(B) (io) is expressed in S. mutans biofilms so understanding its regulation
      may provide improved strategies for caries treatment and prevention.

PMID- 25580876
TI  - Controlling directed self-assembly of gold nanorods in patterned PS-b-PMMA thin
      films.
AB  - We present a facile strategy for the directed self-assembly of gold nanorods
      (AuNRs) in patterned block copolymer (BCP) thin films. Parallel arrangement of
      AuNRs relative to the geometric confinement generated by selective removal of one
      block domain was achieved. Deposition of AuNRs with aspect ratios from 3.3 to 5.8
      was accomplished and the alignment of the NRs within the channels was controlled
      primarily by capillary forces and the channel geometry. Ordered AuNR assembly in
      the BCP pattern can be achieved at high surface coverages, >30%, though the
      surface coverage depends on the aspect ratio of the NRs. Larger NRs align in the
      channels more readily, but pack at slightly lower densities. 

PMID- 25580875
TI  - Managing Ethical Challenges to Mental Health Research in Post-Conflict Settings.
AB  - Recently the World Health Organization (WHO) has highlighted the need to
      strengthen mental health systems following emergencies, including natural and
      manmade disasters. Mental health services need to be informed by culturally
      attuned evidence that is developed through research. Therefore, there is an
      urgent need to establish rigorous ethical research practice to underpin the
      evidence-base for mental health services delivered during and following
      emergencies. 

PMID- 25580877
TI  - The risk and benefit of benzodiazepine use in patients with chronic pain.

PMID- 25580878
TI  - Uranium phosphate biomineralization by fungi.
AB  - Geoactive soil fungi were investigated for phosphatase-mediated uranium
      precipitation during growth on an organic phosphorus source. Aspergillus niger
      and Paecilomyces javanicus were grown on modified Czapek-Dox medium amended with
      glycerol 2-phosphate (G2P) as sole P source and uranium nitrate. Both organisms
      showed reduced growth on uranium-containing media but were able to extensively
      precipitate uranium and phosphorus-containing minerals on hyphal surfaces, and
      these were identified by X-ray powder diffraction as uranyl phosphate species,
      including potassium uranyl phosphate hydrate (KPUO6 .3H2 O), meta-ankoleite
      [(K1.7 Ba0.2 )(UO2 )2 (PO4 )2 .6H2 O], uranyl phosphate hydrate [(UO2 )3 (PO4 )2
      .4H2 O], meta-ankoleite (K(UO2 )(PO4 ).3H2 O), uramphite (NH4 UO2 PO4 .3H2 O) and
      chernikovite [(H3 O)2 (UO2 )2 (PO4 )2 .6H2 O]. Some minerals with a morphology
      similar to bacterial hydrogen uranyl phosphate were detected on A. niger biomass.
      Geochemical modelling confirmed the complexity of uranium speciation, and the
      presence of meta-ankoleite, uramphite and uranyl phosphate hydrate between pH 3
      and 8 closely matched the experimental data, with potassium as the dominant
      cation. We have therefore demonstrated that fungi can precipitate U-containing
      phosphate biominerals when grown with an organic source of P, with the hyphal
      matrix serving to localize the resultant uranium minerals. The findings throw
      further light on potential fungal roles in U and P biogeochemistry as well as the
      application of these mechanisms for element recovery or bioremediation.

PMID- 25580879
TI  - Correlation of radiographic measurements of structures of the equine foot with
      lesions detected on magnetic resonance imaging.
AB  - REASONS FOR PERFORMING STUDY: There are few studies on the correlations between
      radiographic measurements of the foot and abnormalities of specific structures
      found with magnetic resonance imaging (MRI). OBJECTIVES: To document the
      relationship between radiographic measurements of the equine foot and the
      presence of lesions in the foot on MRI. We hypothesised that different
      radiographic measurements would be associated with specific lesions detected by
      MRI. STUDY DESIGN: Retrospective analysis of radiographs and MRI studies.
      METHODS: Seventy-four feet from 52 lame horses were included. Twenty parameters
      were measured on radiographs, whereas the signal intensity, homogeneity and size
      of each structure in the foot were evaluated on magnetic resonance images. The
      data were analysed using simple linear correlation analysis and classification
      and regression trees (CARTs). RESULTS: Linear correlations were found between the
      navicular bone compacta thickness and injuries of the deep digital flexor tendon,
      collateral sesamoidean ligament, navicular spongiosa and navicular bone proximal
      border. Long-toed horses had a high incidence of lesions involving the spongiosa
      and proximal border of the navicular bone. Elongation of the navicular bone was
      associated with proximal and distal border injuries. A reduced palmar angle and
      increased angle between the middle and distal phalanx were observed in horses
      with alterations of collateral ligaments of the distal interphalangeal joint and
      navicular bone spongiosa, respectively. For each structure under investigation,
      CARTs predicting the presence of MRI pathology based on radiographic measurements
      had excellent performance, with >80% correct classification of cases, when using
      one of 3 data sources. CONCLUSIONS: This study demonstrated a relationship
      between radiographic measurements of the foot and the presence of lesions
      detected on MRI, while CARTs illustrated that different radiographic measurements
      were associated with different MRI lesions.

PMID- 25580880
TI  - Subchronic toxicity and cardiovascular responses in spontaneously hypertensive
      rats after exposure to multiwalled carbon nanotubes by intratracheal
      instillation.
AB  - The tremendous demand of the market for carbon nanotubes has led to their massive
      production that presents an increasing risk through occupational exposure. Lung
      deposition of carbon nanotubes is known to cause acute localized pulmonary
      adverse effects. However, systemic cardiovascular damages associated with acute
      pulmonary lesion have not been thoroughly addressed. Four kinds of multiwalled
      carbon nanotubes (MWCNTs) with different lengths and/or iron contents were used
      to explore the potential subchronic toxicological effects in spontaneously
      hypertensive (SH) rats and normotensive control Wistar-Kyoto (WKY) rats after
      intratracheal instillation. MWCNTs penetrated the lung blood-gas barrier and
      accumulated in the liver, kidneys, and spleen but not in the heart and aorta of
      SH rats. The pulmonary toxicity and cardiovascular effects were assessed at 7 and
      30 days postexposure. Compared to the WKY rats, transient influences on blood
      pressure and up to 30 days persistent decrease in the heart rate of SH rats were
      found by electrocardiogram monitoring. The subchronic toxicity, especially the
      sustained inflammation of the pulmonary and cardiovascular system, was revealed
      at days 7 and 30 in both SH and WKY rat models. Histopathological results showed
      obvious morphological lesions in abdominal arteries of SH rats 30 days after
      exposure. Our results suggest that more attention should be paid to the long-term
      toxic effects of MWCNTs, and particularly, occupationally exposed workers with
      preexisting cardiovascular diseases should be monitored more thoroughly. 

PMID- 25580881
TI  - PET2 -driven de-escalation therapy in 64 high-risk Hodgkin Lymphoma patients
      treated with escalated BEACOPP.

PMID- 25580882
TI  - Disability identity predicts lower anxiety and depression in multiple sclerosis.
AB  - PURPOSE/OBJECTIVE: Disability identity involves affirming one's status as a
      person with a disability and incorporating this group membership into one's
      identity. It is associated with well-being in populations of people with
      disabilities, but its relationship with depression and anxiety in multiple
      sclerosis (MS) has yet to be examined. It was hypothesized that disability
      identity would predict lower depression and anxiety above and beyond the effects
      of demographic and disability variables. RESEARCH METHOD/DESIGN: One hundred and
      six participants with MS completed a cross-sectional Internet survey measuring
      disability identity, depression and anxiety, activities of daily living
      performance, MS duration, and demographic variables. Inclusion criteria were as
      follows: self-reported diagnosis of MS, self-reported impairment in walking, age
      18 or older, living in the United States, and English fluency. RESULTS:
      Hierarchical regressions revealed that disability identity was a unique predictor
      of lower depression and anxiety. Older age and higher activities of daily living
      performance also predicted lower depression and anxiety.
      CONCLUSIONS/IMPLICATIONS: Stronger disability identity predicts lower
      psychological distress in MS. Clinical implications include supporting patient
      disability identity by encouraging involvement in disability support and advocacy
      groups. Future research should examine psychosocial interventions to affirm
      identity.

PMID- 25580883
TI  - Characterizing generated charged inverse micelles with transient current
      measurements.
AB  - We investigate the generation of charged inverse micelles in nonpolar surfactant
      solutions relevant for applications such as electronic ink displays and liquid
      toners. When a voltage is applied across a thin layer of a nonpolar surfactant
      solution between planar electrodes, the generation of charged inverse micelles
      leads to a generation current. From current measurements it appears that such
      charged inverse micelles generated in the presence of an electric field behave
      differently compared to those present in equilibrium in the absence of a field.
      To examine the origin of this difference, transient current measurements in which
      the applied voltage is suddenly increased are used to measure the mobility and
      the amount of generated charged inverse micelles. The mobility and the
      corresponding hydrodynamic size are found to be similar to those of charged
      inverse micelles present in equilibrium, which indicates that other properties
      determine their different behavior. The amplitude and shape of the transient
      currents measured as a function of the surfactant concentration confirm that the
      charged inverse micelles are generated by bulk disproportionation. A theoretical
      model based on bulk disproportionation with simulations and analytical
      approximations is developed to analyze the experimental transient currents. 

PMID- 25580885
TI  - Prediction of nonradical Au(0)-containing precursors in nanoparticle growth
      processes.
AB  - This density functional theory (DFT) investigation examines the formation of
      nonradical Au(0) species from the reduction of Au(I) species. The Au(I) complexes
      of interest are AuCl2(-), AuBr2(-), AuI2(-), AuClPH3, and AuCl(H)SCH3(-), which
      are precursors for gold nanoparticle and cluster formation. Reaction of two of
      the Au(I) species with a hydride results in ejection of two of the ligands and
      formation of Au2 with two ligands still attached. AuX2(-) (where X = Cl, Br, or
      I) reactions eject two halides and form Au2X2(2-). AuClL(-) (where L = PH3,
      HSCH3, or SCH3(-)) reactions can eject either chloride, HCl, PH3, HSCH3, or SCH3(
      ) and form Au(0)L2(q-) or Au(0)ClL(q-) (q = 0, 1, 2). The Au2Cl2(2-) complex can
      further react with AuCl2(-), which forms Au3Cl3(2-) and a chloride anion. The new
      Au3Cl3(2-) species can then react with AuCl2(-) or Au2Cl2(2-) or with another
      Au3Cl3(2-). Larger clusters can be formed from these precursors. In this work,
      reactions in both methanol and benzene solvents are considered as models for one
      phase and two-phase gold nanoparticle growth processes. Overall, this
      investigation shows how Au(0)-containing species can be formed without assuming
      the formation of Au(0) atoms (radical species).

PMID- 25580886
TI  - Catalyst orientation-induced growth of defect-free zinc-blende structured ?001?
      InAs nanowires.
AB  - In this study, we demonstrate the epitaxial growth of ?001? defect-free zinc
      blende structured InAs nanowires on GaAs {111}B substrate using Au catalysts in
      molecular beam epitaxy. It has been found that the catalysts and their underlying
      ?001? nanowires have the orientation relationship of {1103}C//{002}InAs and
      [3302]C//[110]InAs due to their small in-plane lattice mismatches between their
      corresponding lattice spacings perpendicular to the {001} atomic planes of the
      nanowires, leading to the formation of the {001} catalyst/nanowire interfaces,
      and consequently the formation of ?001? nanowires. This study provides a
      practical approach to manipulate the crystal structure and structural quality of
      III-V nanowires through carefully controlling the crystal phase of the catalysts.

PMID- 25580884
TI  - The opposing roles of NOTCH signalling in head and neck cancer: a mini review.
AB  - NOTCH signalling can exert oncogenic or tumour suppressive effects in both solid
      and haematological malignancies. Similar to T-cell acute lymphoblastic leukaemia
      (T-ALL), early studies suggested a pro-tumorigenic role of NOTCH in head and neck
      squamous cell carcinoma (HNSCC), mainly based on the increased expression levels
      of the genes within the pathway. Recently, data from exome sequencing analyses
      unexpectedly pointed to a tumour suppressor role for NOTCH in HNSCC by
      identifying loss-of-function mutations in the NOTCH1 gene in a significant
      proportion of patients. These data have questioned the accepted role of NOTCH in
      HNSCC and the possible rationale of targeting NOTCH in this disease. This review
      summarises the current information on NOTCH signalling in HNSCC and discusses how
      this pathway can apparently exert opposing effects within the same disease. 

PMID- 25580887
TI  - Clinical Use of an Optical Coherence Tomography Linear Discriminant Function for
      Differentiating Glaucoma From Normal Eyes.
AB  - PURPOSE: To determine and validate the diagnostic ability of a linear
      discriminant function (LDF) based on retinal nerve fiber layer (RNFL) and
      ganglion cell-inner plexiform layer (GCIPL) thickness obtained using high
      definition optical coherence tomography (Cirrus HD-OCT) for discriminating
      between healthy controls and early glaucoma subjects. METHODS: We prospectively
      selected 214 healthy controls and 152 glaucoma subjects (teaching set) and
      another independent sample of 86 healthy controls and 71 glaucoma subjects
      (validating set). Two scans, including 1 macular and 1 peripapillary RNFL scan,
      were obtained. After calculating the LDF in the teaching set using the binary
      logistic regression analysis, receiver operating characteristic curves were
      plotted and compared between the OCT-provided parameters and LDF in the
      validating set. RESULTS: The proposed LDF was 16.529-(0.132*superior RNFL)
      (0.064*inferior RNFL)+(0.039*12 o'clock RNFL)+(0.038*1 o'clock
      RNFL)+(0.084*superior GCIPL)-(0.144*minimum GCIPL). The highest area under the
      receiver operating characteristic (AUROC) curve was obtained for LDF in both sets
      (AUROC=0.95 and 0.96). In the validating set, the LDF showed significantly higher
      AUROC than the best RNFL (inferior RNFL=0.91) and GCIPL parameter (minimum
      GCIPL=0.88). The LDF yielded a sensitivity of 93.0% at a fixed specificity of
      85.0%. CONCLUSIONS: The LDF showed better diagnostic ability for differentiating
      between healthy and early glaucoma subjects than individual OCT parameters. A
      classification algorithm based on the LDF can be used in the OCT analysis for
      glaucoma diagnosis.

PMID- 25580888
TI  - Long-term Outcomes After Preoperative Intravitreal Injection of Bevacizumab
      Before Trabeculectomy for Neovascular Glaucoma.
AB  - PURPOSE: To evaluate the long-term (>3 y) outcomes of patients given preoperative
      intravitreal bevacizumab (IVB) injection before trabeculectomy for neovascular
      glaucoma (NVG). METHOD: We performed a retrospective study of a consecutive
      series of 12 eyes of 11 patients who underwent trabeculectomy with mitomycin C
      combined with preoperative IVB for NVG at our institution between April 2009 and
      April 2010. The mean follow-up period was 43.0+/-7.0 months (range, 36 to 51 mo),
      and all patients were followed up for at least 36 months. Surgical success was
      defined as an intraocular pressure (IOP) of <=21 mm Hg with or without topical
      ocular hypotensive medication. RESULT: The cumulative surgical success rate was
      83.3% at 1 year and 83.3% at 3 years. The mean IOP before surgery was 42.7+/-9.2
      mm Hg, whereas the mean postoperative IOP was significantly lower, being 15.1+/
      3.7 mm Hg at 1 year and 14.2+/-3.2 mm Hg at 3 years (P<0.01).In contrast, no
      significant change of the mean visual acuity as compared with the preoperative
      visual acuity was observed at the follow-up carried out 3 years after the
      surgery. Intraoperative and early postoperative hyphema was seen in 2 eyes.
      Recurrence of neovascularization requiring additional IVB injection was seen in 3
      eyes. CONCLUSIONS: Preoperative IVB injection before trabeculectomy for NVG might
      be effective over the long-term (>3 y) control of the IOP.

PMID- 25580889
TI  - Is Myopic Optic Disc Appearance a Risk Factor for Rapid Progression in Medically
      Treated Glaucomatous Eyes With Confirmed Visual Field Progression?
AB  - PURPOSE: To investigate visual field (VF) progression rates in glaucomatous eyes
      with myopic optic disc appearance, refractive error, and progressive VF changes
      and to compare the rates with those of a nonmyopic group. PATIENTS AND METHODS:
      Data on 158 eyes from 131 patients with open-angle glaucoma who had progressive
      VF deterioration during follow-up were retrospectively analyzed. The myopic and
      nonmyopic groups were compared in terms of rates of change of mean thresholds in
      global and regional areas using central 10 degrees, peripheral 10 to 24 degrees,
      and glaucoma hemifield test maps by using a linear-mixed model and controlling
      for confounding covariates. Clinical factors associated with rapid VF progression
      at global and regional VF areas were investigated in each group. RESULTS: The 2
      groups did not significantly differ in the mean global VF progression rate (-0.36
      vs. -0.35 dB/y, respectively; P=0.951). Likewise, both groups showed similar VF
      progression rates at all regional clusters (P>0.05). No significant association
      was found between the rate of VF change and clinical factors in the myopic group.
      The mean follow-up intraocular pressure was significantly associated with VF
      progression rates in the nonmyopic group (P<0.05). CONCLUSIONS: Open-angle
      glaucoma eyes with myopic optic disc appearance experiencing progressive VF
      changes showed similar VF progression rates globally and regionally when compared
      with nonmyopic eyes after controlling for clinical factors related to VF
      progression. None of the clinical factors in the myopic group were significantly
      associated with VF progression rate, whereas the mean follow-up intraocular
      pressure was in the nonmyopic group.

PMID- 25580890
TI  - Effects of Axial Length and Age on Circumpapillary Retinal Nerve Fiber Layer and
      Inner Macular Parameters Measured by 3 Types of SD-OCT Instruments.
AB  - PURPOSES: To evaluate the effects of axial length and age on the circumpapillary
      retinal nerve fiber layer (cpRNFL) and the inner macular parameters measured
      using 3 spectral-domain optical coherence tomography (OCT) instruments. METHODS:
      A total of 102 normal eyes (1 eye per subject) were imaged using Cirrus, RTVue,
      and 3D-OCT. The cpRNFL and the macular retinal nerve fiber layer (mRNFL), the
      ganglion cell layer+inner plexiform layer (GCLIPL), and the mRNFL+GCLIPL ganglion
      cell complex, GCC thicknesses were analyzed. The correlations between these
      values and the axial length or age were evaluated using a partial correlation
      analysis. These correlations were corrected using the axial length-related
      magnification effect. RESULTS: All but the nasal quadrant cpRNFL thicknesses and
      GCC thicknesses obtained using the 3 OCT instruments were significantly
      correlated with age. The average cpRNFL thickness and GCC thickness measured
      using the Cirrus and RTVue, but not by the 3D-OCT, had a negative correlation
      with the axial length. The temporal quadrant cpRNFL thickness measured using the
      3 instruments was positively correlated with the axial length. The magnification
      correction made the most correlations positive. CONCLUSIONS: The average cpRNFL
      and GCC thicknesses measured using these 3 instruments decreased with age. The
      axial length affected the cpRNFL and GCC thicknesses as measured using the Cirrus
      and RTVue; this effect likely depended on the fundus area of analyses.

PMID- 25580891
TI  - Phenotype and Genotype Correlation in Iranian Primary Congenital Glaucoma
      Patients.
AB  - PURPOSE: To explore the correlation between clinical manifestations of primary
      congenital glaucoma (PCG) and CYP1B1 mutations. METHODS: A clinical and molecular
      genetic study was performed on a cohort of 17 patients with PCG and known CYP1B1
      mutation profile including 10 subjects with and 7 cases without mutations.
      Ophthalmolgical records were reviewed and phenotype which was defined by age at
      onset, presenting intraocular pressure (IOP), corneal diameter, and vertical cup
      to disc ratio, and the number of procedures was correlated with the presence or
      absence of CYP1B1 mutations. RESULTS: Overall, 8 mutations were identified in 10
      patients. The disease became manifest earlier than 1 month of age in 9 of 10
      (90%) cases with, as compared with 2 of 7 (28.6%) patients without mutations
      (P=0.035). Baseline IOP was 29.3+/-6.5 mm Hg in the mutation-positive group
      versus 17.6+/-3.7 mm Hg in subjects without mutations (P<0.001). Patients with
      mutations also had significantly higher IOP throughout follow-up (P<0.002). The
      number of operations was significantly higher in subjects with mutations (3.3+/
      1.8 vs. 1.8+/-1.5 procedures, P=0.025). Six patients (60%) with mutations were
      female as compared with 1 subject (14.3%) in the nonmutation group (P=0.134).
      There was no significant difference between the study groups in terms of corneal
      diameter (P=0.475) and vertical cup to disc ratio (P=0.794). CONCLUSIONS: PCG
      patients with CYP1B1 mutations seem to have earlier onset disease, display more
      severe manifestations, and require more operations as compared with subjects
      without such mutations. These findings may have implications in prognosticating
      the disease and genetic counseling.

PMID- 25580893
TI  - Lehmann S, Uhlemann M, Etz CD, et al. Extracorporeal membrane oxygenation:
      experience in acute graft failure after heart transplantation. Clin Transplant.
      2014; 28(7):789-96.

PMID- 25580892
TI  - A Survey on the Preference of Sustained Glaucoma Drug Delivery Systems by
      Singaporean Chinese Patients: A Comparison Between Subconjunctival, Intracameral,
      and Punctal Plug Routes.
AB  - PURPOSE: To investigate the acceptance and preferences rates of 3 sustained drug
      delivery systems in glaucoma patients. MATERIALS AND METHODS: A cross-sectional
      study involving 250 Chinese patients recruited from outpatient glaucoma clinics
      in Singapore using an interviewer-administered survey. Beliefs toward medicines,
      eye drops, illness perception, medication adherence, and health literacy were
      assessed using validated questionnaires. After receiving standard information on
      the 3 sustained drug delivery systems, that is, subconjunctival, intracameral,
      and punctal routes; each route's acceptance and attitudes were determined.
      RESULTS: The subconjunctival (acceptance: 61.6%, n=154), intracameral
      (acceptance: 57.2%, n=143), and punctal (acceptance: 63.2%, n=158) routes were
      willing to be accepted by the majority of the interviewed patients. Among those,
      78.6%, 79.1%, and 78.5% were willing to pay an equal or higher cost compared with
      their current eye drops for the subconjunctival, intracameral, and punctal plug
      routes, respectively. Independent factors associated with the acceptance for
      subconjunctival, intracameral, and punctal plug routes included: male sex
      (P=0.007, 0.014, 0.046, respectively), patients not on health care subsidies
      (P=0.022, 0.002, 0.016, respectively), and bilateral glaucoma disease (P=0.003,
      0.013, 0.004, respectively). A total of 120 (48.0%) patients ranked punctal plug
      placement as the preferred route for sustained drug delivery followed by
      subconjunctival (n=76, 30.4%) and intracameral (n=54, 21.6%) routes. CONCLUSIONS:
      Sustained drug delivery for the medical treatment of glaucoma is an acceptable
      alternative to daily eye drop administration by most Singaporean Chinese
      individuals in this study. Male patients, nonsubsidized patients, and those with
      bilateral glaucoma were independently associated with preference of these 3
      alternative routes of administration to traditional glaucoma drops.

PMID- 25580894
TI  - General strategy for the synthesis of B1 and L1 prostanoids: synthesis of
      phytoprostanes (RS)-9-L1-PhytoP, (R)-9-L1-PhytoP, (RS)-16-B1-PhytoP, and (RS)-16
      L1-PhytoP.
AB  - In this paper we describe a novel general synthetic approach to B1- and L1-type
      phytoprostanes, which are formed in vivo from free-radical-catalyzed nonenzymatic
      peroxidation of alpha-linolenic acid (1). The synthesis of phytoprostanes (RS)-9
      L1-PhytoP (5), (R)-9-L1-PhytoP (5a), (RS)-16-B1-PhytoP (6), and (RS)-16-L1-PhytoP
      (7) exemplifies this strategy. The common starting compound 8 has been proved to
      be synthetically equivalent to a cyclopent-2-en-1-one synthon having opposite
      donor and acceptor properties at carbons alpha and beta, respectively. Key steps
      include the chemoselective lithiation of a 1-iodo-2-bromoolefin, the introduction
      of the side chains by transition-metal catalysis following Heck- or Suzuki-type
      protocols, the construction of an enone moiety by a mild Au(I)-catalyzed Meyer
      Schuster rearrangement, and a lipase-mediated hydrolysis of methyl esters to
      deliver the phytoprostanes as free carboxylic acids. 

PMID- 25580895
TI  - Phototriggerable peptidomimetics for the inhibition of Mycobacterium tuberculosis
      ribonucleotide reductase by targeting protein-protein binding.
AB  - Incorporation of an artificial amino acid 2 with a stilbene chromophore into
      peptidomimetics with three to nine amino acids yields phototriggerable candidates
      for inhibition of the binding between the R1 and R2 subunits of the M.
      tuberculosis ribonucleotide reductase (RNR). Interstrand hydrogen bond
      probability was used as a guideline for predicting conformational preferences of
      the photoisomers. Binding of these inhibitors has been rationalized by docking
      studies with the R1 unit. Significant differences in binding of the photoisomers
      were observed. For the shorter peptidomimetics, stronger binding of the Z isomer
      might indicate hydrophobic interactions between the stilbene chromophore and the
      binding site.

PMID- 25580896
TI  - Review of the correlation between blood flow velocity and polycythemia in the
      fetus, neonate and adult: appropriate diagnostic levels need to be determined for
      twin anemia-polycythemia sequence.
AB  - Twin anemia-polycythemia sequence (TAPS) is recognized increasingly antenatally
      by the demonstration of an anemic twin and a polycythemic cotwin using the middle
      cerebral artery peak systolic velocity (MCA-PSV). While the MCA-PSV has been
      shown to correlate well with anemia in singleton fetuses, the evidence to support
      its use to diagnose fetal polycythemia appears to be less clear-cut. We aimed to
      evaluate fetal, neonatal and adult literature used to support the use of MCA-PSV
      for the diagnosis of polycythemia. Comprehensive literature searches were
      performed for ultrasound evidence of polycythemia in the human fetus, neonate and
      adult using key search terms. Only manuscripts in the English language with an
      abstract were considered for the review, performed in June 2014. Fifteen
      manuscripts were found for the human fetus, including 38 cases of TAPS. Nine of
      these defined fetal polycythemia as MCA-PSV < 0.8 multiples of the median (MoM),
      five used < 1.0 MoM and one used 0.8-1.0 MoM. Only two studies, involving a total
      of 15 cases, proposed a diagnostic level, acknowledging false-positive and 
      negative cases, though neither reported sensitivities or specificities. Six
      neonatal studies (96 neonates) demonstrated evidence of decreased cerebral
      velocities in polycythemia and a consequent increase with hemodilution. In the
      adult, five studies (57 polycythemic adults) demonstrated increased flow or
      velocity with hemodilution. Neither neonatal nor adult studies conclusively
      defined levels for screening for polycythemia. Despite widespread adoption of a
      cut-off of < 0.8 MoM in the published literature for the polycythemic fetus in
      TAPS, this is based upon minimal evidence, with unknown sensitivity and
      specificity. We recommend caution in excluding TAPS based purely upon the absence
      of a reduced MCA-PSV.

PMID- 25580897
TI  - Experimental transmission of equine hepacivirus in horses as a model for
      hepatitis C virus.
AB  - Equine hepacivirus (EHCV; nonprimate hepacivirus) is a hepatotropic member of the
      Flaviviridae family that infects horses. Although EHCV is the closest known
      relative to hepatitis C virus (HCV), its complete replication kinetics in vivo
      have not been described, and direct evidence that it causes hepatitis has been
      lacking. In this study, we detected EHCV in 2 horses that developed post
      transfusion hepatitis. Plasma and serum from these horses were used to
      experimentally transmit EHCV to 4 young adult Arabian horses, two 1-month-old
      foals (1 Arabian and 1 Arabian-pony cross), and 2 foals (1 Arabian and 1 Arabian
      pony cross) with severe combined immunodeficiency (SCID). Our results
      demonstrated that EHCV had infection kinetics similar to HCV and that infection
      was associated with acute and chronic liver disease as measured by elevations of
      liver-specific enzymes and/or by histopathology. Although most of these animals
      were coinfected with equine pegivirus (EPgV), also a flavivirus, EPgV viral loads
      were much lower and often undetectable in both liver and blood. Three additional
      young adult Arabian-pony crosses and 1 SCID foal were then inoculated with plasma
      containing only EHCV, and evidence of mild hepatocellular damage was observed.
      The different levels of liver-specific enzyme elevation, hepatic inflammation,
      and duration of viremia observed during EHCV infection suggested that the
      magnitude and course of liver disease was mediated by the virus inoculum and/or
      by host factors, including breed, age, and adaptive immune status. CONCLUSION:
      This work documents the complete infection kinetics and liver pathology
      associated with acute and chronic EHCV infection in horses and further justifies
      it as a large animal model for HCV.

PMID- 25580898
TI  - Aggregation behavior and total miscibility of fluorinated ionic liquids in water.
AB  - In this work, novel and nontoxic fluorinated ionic liquids (FILs) that are
      totally miscible in water and could be used in biological applications, where
      fluorocarbon compounds present a handicap because their aqueous solubility (water
      and biological fluids) is in most cases too low, have been investigated. The self
      aggregation behavior of perfluorosulfonate-functionalized ionic liquids in
      aqueous solutions has been characterized using conductometric titration,
      isothermal titration calorimetry (ITC), surface tension measurements, dynamic
      light scattering (DLS), viscosity and density measurements, and transmission
      electron microscopy (TEM). Aggregation and interfacial parameters have been
      computed by conductimetry, calorimetry, and surface tension measurements in order
      to study various thermodynamic and surface properties that demonstrate that the
      aggregation process is entropy-driven and that the aggregation process is less
      spontaneous than the adsorption process. The novel perfluorosulfonate
      functionalized ILs studied in this work show improved surface activity and
      aggregation behavior, forming distinct self-assembled structures. 

PMID- 25580899
TI  - Three-dimensional object motion and velocity estimation using a single
      computational RGB-D camera.
AB  - In this paper, a three-dimensional (3D) object moving direction and velocity
      estimation method is presented using a dual off-axis color-filtered aperture
      (DCA)-based computational camera. Conventional object tracking methods provided
      only two-dimensional (2D) states of an object in the image for the target
      representation. The proposed method estimates depth information in the object
      region from a single DCA camera that transforms 2D spatial information into 3D
      model parameters of the object. We also present a calibration method of the DCA
      camera to estimate the entire set of camera parameters for a practical
      implementation. Experimental results show that the proposed DCA-based color and
      depth (RGB-D) camera can calculate the 3D object moving direction and velocity of
      a randomly moving object in a single-camera framework. 

PMID- 25580900
TI  - Selective recognition of 5-hydroxytryptamine and dopamine on a multi-walled
      carbon nanotube-chitosan hybrid film-modified microelectrode array.
AB  - It is difficult to determine dopamine (DA) and 5-hydroxytryptamine (5-HT)
      accurately because of the interference of ascorbic acid (AA) in vitro, which has
      a high concentration and can be oxidized at a potential close to DA and 5-HT at a
      conventional electrode, combined with the overlapping voltammetric signal of DA
      and 5-HT at a bare electrode. Herein, chitosan (CS) was used as a stabilizing
      matrix by electrochemical reaction, and multi-walled carbon nanotubes (MWCNTs)
      were modified onto the microelectrode array (MEA). The CS-MWCNT hybrid film
      modified MEA was quite effective at simultaneously recognizing these species in a
      mixture and resolved the overlapping anodic peaks of AA, DA and 5-HT into three
      well-defined oxidation peaks in differential pulse voltammetry (DPV) at -80 mV,
      105 mV and 300 mV (versus Ag|AgCl), respectively. The linear responses were
      obtained in the range of 5 * 10(-6) M to 2 * 10(-4) M for DA (r = 0.996) and in
      the range of 1 * 10(-5) M to 3 * 10(-4) M for 5-HT (r = 0.999) using the DPV
      under the presence of a single substance. While DA coexisted with 5-HT in the
      interference of 3 * 10(-4) M AA, the linear responses were obtained in the range
      of 1 * 10(-5) M to 3 * 10(-4) M for selective molecular recognition of DA (r =
      0.997) and 5-HT (r = 0.997) using the DPV. Therefore, this proposed MEA was
      successfully used for selective molecular recognition and determination of DA and
      5-HT using the DPV, which has a potential application for real-time determination
      in vitro experiments.

PMID- 25580901
TI  - Depth camera-based 3D hand gesture controls with immersive tactile feedback for
      natural mid-air gesture interactions.
AB  - Vision-based hand gesture interactions are natural and intuitive when interacting
      with computers, since we naturally exploit gestures to communicate with other
      people. However, it is agreed that users suffer from discomfort and fatigue when
      using gesture-controlled interfaces, due to the lack of physical feedback. To
      solve the problem, we propose a novel complete solution of a hand gesture control
      system employing immersive tactile feedback to the user's hand. For this goal, we
      first developed a fast and accurate hand-tracking algorithm with a Kinect sensor
      using the proposed MLBP (modified local binary pattern) that can efficiently
      analyze 3D shapes in depth images. The superiority of our tracking method was
      verified in terms of tracking accuracy and speed by comparing with existing
      methods, Natural Interaction Technology for End-user (NITE), 3D Hand Tracker and
      CamShift. As the second step, a new tactile feedback technology with a
      piezoelectric actuator has been developed and integrated into the developed hand
      tracking algorithm, including the DTW (dynamic time warping) gesture recognition
      algorithm for a complete solution of an immersive gesture control system. The
      quantitative and qualitative evaluations of the integrated system were conducted
      with human subjects, and the results demonstrate that our gesture control with
      tactile feedback is a promising technology compared to a vision-based gesture
      control system that has typically no feedback for the user's gesture inputs. Our
      study provides researchers and designers with informative guidelines to develop
      more natural gesture control systems or immersive user interfaces with haptic
      feedback. 

PMID- 25580902
TI  - Accelerated detection of viral particles by combining AC electric field effects
      and micro-Raman spectroscopy.
AB  - A detection method that combines electric field-assisted virus capture on
      antibody-decorated surfaces with the "fingerprinting" capabilities of micro-Raman
      spectroscopy is demonstrated for the case of M13 virus in water. The proof-of
      principle surface mapping of model bioparticles (protein coated polystyrene
      spheres) captured by an AC electric field between planar microelectrodes is
      presented with a methodology for analyzing the resulting spectra by comparing
      relative peak intensities. The same principle is applied to dielectrophoretically
      captured M13 phage particles whose presence is indirectly confirmed with micro
      Raman spectroscopy using NeutrAvidin-Cy3 as a labeling molecule. It is concluded
      that the combination of electrokinetically driven virus sampling and micro-Raman
      based signal transduction provides a promising approach for time-efficient and in
      situ detection of viruses. 

PMID- 25580903
TI  - A sensor-type PC strand with an embedded FBG sensor for monitoring prestress
      forces.
AB  - Prestressed Concrete Wire and Strand (PC) strands are the most used materials to
      introduce prestress in a Pre-Stressed Concrete (PSC) structure. However, it is
      difficult to evaluate the final prestress force of the PC strand after
      prestressing or its residual prestress force after completion of the structure on
      site. This impossibility to assess eventual loss of prestress of the PC strand
      has resulted in a number of serious accidents and even in the collapse of several
      structures. This situation stresses the necessity to maintain the prestress force
      residual or after prestressing for the evaluation of the health of the concrete
      structure throughout its lifespan. Recently, several researchers have studied
      methods enabling one to verify the prestress force by inserting an optical fiber
      sensor inside the strand but failed to provide simple techniques for the
      fabrication of these devices to fulfill measurement performance from the design
      prestress to failure. Moreover, these methods require the additional installation
      of electrical resistance strain gages, displacement sensors and load cells on the
      outer surface of the structure for long-term precise measurement. This paper
      proposes a method enabling one to evaluate precisely and effectively the
      prestress force of the PC strand and intends to verify the applicability of the
      proposed method on actual concrete structures. To that end, an innovative PC
      strand is developed by embedding a Fiber Bragg Grating (FBG) sensor in the core
      wire of the PC strand so as to enable short term as well as long term monitoring.
      The measurement performance of the developed strand is then evaluated
      experimentally and the reliability of the monitoring data is assessed. 

PMID- 25580904
TI  - Single-sample face recognition based on intra-class differences in a variation
      model.
AB  - In this paper, a novel random facial variation modeling system for sparse
      representation face recognition is presented. Although recently Sparse
      Representation-Based Classification (SRC) has represented a breakthrough in the
      field of face recognition due to its good performance and robustness, there is
      the critical problem that SRC needs sufficiently large training samples to
      achieve good performance. To address these issues, we challenge the single-sample
      face recognition problem with intra-class differences of variation in a facial
      image model based on random projection and sparse representation. In this paper,
      we present a developed facial variation modeling systems composed only of various
      facial variations. We further propose a novel facial random noise dictionary
      learning method that is invariant to different faces. The experiment results on
      the AR, Yale B, Extended Yale B, MIT and FEI databases validate that our method
      leads to substantial improvements, particularly in single-sample face recognition
      problems. 

PMID- 25580905
TI  - WhiteRef: a new tower-based hyperspectral system for continuous reflectance
      measurements.
AB  - Proximal sensing is fundamental to monitor the spatial and seasonal dynamics of
      ecosystems and can be considered as a crucial validation tool to upscale in situ
      observations to the satellite level. Linking hyperspectral remote sensing with
      carbon fluxes and biophysical parameters is critical to allow the exploitation of
      spatial and temporal extensive information for validating model simulations at
      different scales. In this study, we present the WhiteRef, a new hyperspectral
      system designed as a direct result of the needs identified during the EUROSPEC
      ES0903 Cost Action, and developed by Fondazione Edmund Mach and the Institute of
      Biometeorology, CNR, Italy. The system is based on the ASD FieldSpec Pro
      spectroradiometer and was designed to acquire continuous radiometric measurements
      at the Eddy Covariance (EC) towers and to fill a gap in the scientific community:
      in fact, no system for continuous spectral measurements in the Short Wave
      Infrared was tested before at the EC sites. The paper illustrates the functioning
      of the WhiteRef and describes its main advantages and disadvantages. The WhiteRef
      system, being based on a robust and high quality commercially available
      instrument, has a clear potential for unattended continuous measurements aiming
      at the validation of satellites' vegetation products. 

PMID- 25580907
TI  - Enhanced light scattering and trapping effect of Ag nanowire mesh electrode for
      high efficient flexible organic solar cell.
AB  - Ag nanowire (NW) mesh is used as transparent conducting electrode for high
      efficient flexible organic solar cells (OSCs). The Ag NW mesh electrode
      facilitates light scattering and trapping, allowing enhancement of light
      absorption in the active layer. OSCs incorporating Ag NW mesh electrode exhibit
      maximum power conversion efficiency (PCE) of 4.47%, 25%, higher than that of OSCs
      with a conventional ITO electrode (3.63%). 

PMID- 25580906
TI  - Novel 3-nitrotriazole-based amides and carbinols as bifunctional antichagasic
      agents.
AB  - 3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3
      nitrotriazole-based fluconazole analogues were synthesized as dual functioning
      antitrypanosomal agents. Such compounds are excellent substrates for type I
      nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the
      same time, act as inhibitors of the sterol 14alpha-demethylase (T. cruzi CYP51)
      enzyme. Because combination treatments against parasites are often superior to
      monotherapy, we believe that this emerging class of bifunctional compounds may
      introduce a new generation of antitrypanosomal drugs. In the present work, the
      synthesis and in vitro and in vivo evaluation of such compounds is discussed. 

PMID- 25580909
TI  - Origin of stereocontrol in guanidine-bisurea bifunctional organocatalyst that
      promotes alpha-hydroxylation of tetralone-derived beta-ketoesters: asymmetric
      synthesis of beta- and gamma-substituted tetralone derivatives via
      organocatalytic oxidative kinetic resolution.
AB  - The mechanism of asymmetric alpha-hydroxylation of tetralone-derived beta
      ketoesters with guanidine-bisurea bifunctional organocatalyst in the presence of
      cumene hydroperoxide (CHP) was examined by means of DFT calculations to
      understand the origin of the stereocontrol in the reaction. The identified
      transition-state model was utilized to design an enantioselective synthesis of
      beta- or gamma-substituted tetralones by catalytic oxidative kinetic resolution
      reaction of tetralone-derived beta-ketoesters. This kinetic resolution reaction
      proceeded with high selectivity, and selectivity factors (s value) of up to 99
      were obtained. The potential utility of this oxidative kinetic resolution method
      for synthesis of natural products was confirmed by applying it to achieve an
      enantioselective synthesis of (+)-linoxepin (13) from beta-substituted tetralone
      rac-7 in only six steps. 

PMID- 25580908
TI  - Association of valine and leucine at HLA-DRB1 position 11 with radiographic
      progression in rheumatoid arthritis, independent of the shared epitope alleles
      but not independent of anti-citrullinated protein antibodies.
AB  - OBJECTIVE: For decades it has been known that the HLA-DRB1 shared epitope (SE)
      alleles are associated with an increased risk of development and progression of
      rheumatoid arthritis (RA). Recently, the following variations in the peptide
      binding grooves of HLA molecules that predispose to RA development have been
      identified: Val and Leu at HLA-DRB1 position 11, Asp at HLA-B position 9, and Phe
      at HLA-DPB1 position 9. This study was undertaken to investigate whether these
      variants are also associated with radiographic progression in RA, independent of
      SE and anti-citrullinated protein antibody (ACPA) status. METHODS: A total of
      4,911 radiograph sets from 1,878 RA patients included in the Leiden Early
      Arthritis Clinic (The Netherlands), Umea (Sweden), Hospital Clinico San Carlos
      Rheumatoid Arthritis (Spain), and National Data Bank for Rheumatic Diseases (US)
      cohorts were studied. HLA was imputed using single-nucleotide polymorphism data
      from an Immunochip, and the amino acids listed above were tested in relation to
      radiographic progression per cohort using an additive model. Results from the 4
      cohorts were combined in inverse-variance weighted meta-analyses using a fixed
      effects model. Analyses were conditioned on SE and ACPA status. RESULTS: Val and
      Leu at HLA-DRB1 position 11 were associated with more radiographic progression
      (meta-analysis P = 5.11 * 10(-7)); this effect was independent of SE status (meta
      analysis P = 0.022) but not independent of ACPA status. Phe at HLA-DPB1 position
      9 was associated with more severe radiographic progression (meta-analysis P =
      0.024), though not independent of SE status. Asp at HLA-B position 9 was not
      associated with radiographic progression. CONCLUSION: Val and Leu at HLA-DRB1
      position 11 conferred a risk of a higher rate of radiographic progression
      independent of SE status but not independent of ACPA status. These findings
      support the relevance of these amino acids at position 11.

PMID- 25580910
TI  - Nitrosopurines en route to potently cytotoxic asmarines.
AB  - A nitrosopurine ene reaction easily assembles the asmarine pharmacophore and
      transmits remote stereochemistry to the diazepine-purine hetereocycle. This
      reaction generates potent cytotoxins which exceed the potency of asmarine A (1.2
      MUM IC50) and supersede the metabolites as useful leads for biological discovery.

PMID- 25580911
TI  - Luminescent Ag6Au6 heterometallic ethisterone cluster and probe for estrogen
      receptor alpha.
AB  - A heterometallic cluster [Ag6Au6(ethisterone)12] of an unprecedented topology was
      synthesized and characterized. A sensitive and specific probe for estrogen
      receptor alpha (ERalpha) has been developed for the first time based on the
      enhancement of the Ag6Au6 luminescence.

PMID- 25580912
TI  - Encapsulation of enzyme via one-step template-free formation of stable organic
      inorganic capsules: A simple and efficient method for immobilizing enzyme with
      high activity and recyclability.
AB  - Enzyme encapsulation is a simple, gentle, and general method for immobilizing
      enzyme, but it often suffers from one or more problems regarding enzyme loading
      efficiency, enzyme leakage, mechanical stability, and recyclability. Here we
      report a novel, simple, and efficient method for enzyme encapsulation to overcome
      these problems by forming stable organic-inorganic hybrid capsules. A new,
      facile, one-step, and template-free synthesis of organic-inorganic capsules in
      aqueous phase were developed based on PEI-induced simultaneous interfacial self
      assembly of Fmoc-FF and polycondensation of silicate. Addition of an aqueous
      solution of Fmoc-FF and sodium silicate into an aqueous solution of PEI gave a
      new class of organic-inorganic hybrid capsules (FPSi) with multi-layered
      structure in high yield. The capsules are mechanically stable due to the
      incorporation of inorganic silica. Direct encapsulation of enzyme such as epoxide
      hydrolase SpEH and BSA along with the formation of the organic-inorganic capsules
      gave high yield of enzyme-containing capsules (~1.2 mm in diameter), >90% enzyme
      loading efficiency, high specific enzyme loading (158 mg protein g(-1) carrier),
      and low enzyme leakage (<3% after 48 h incubation). FPSi-SpEH capsules catalyzed
      the hydrolysis of cyclohexene oxide to give (1R, 2R)-cyclohexane-1,2-diol in high
      yield and concentration, with high specific activity (6.94 U mg(-1) protein) and
      the same high enantioselectivity as the free enzyme. The immobilized SpEH
      demonstrated also excellent operational stability and recyclability: retaining
      87% productivity after 20 cycles with a total reaction time of 80 h. The new
      enzyme encapsulation method is efficient, practical, and also better than other
      reported encapsulation methods.

PMID- 25580913
TI  - Using tissue samples for proteomic studies-critical considerations.
AB  - From my experience of 22 years working in a pathology research laboratory and
      overseeing dozens of collaborations with research groups from basic sciences and
      industry, I have the impression that researchers are rarely aware of the special
      issues related to acquisition and processing of frozen or formalin-fixed tissue
      samples for proteomic analysis. While challenges are expected for formalin-fixed
      tissues because of the cross-linking activities of formaldehyde, researchers
      believe when using frozen tissue samples they are safe and always have excellent
      material to analyze-but this is not always the case. It is alarming that many
      researchers do not question the quality of the tissue samples they are analyzing
      and focus only on their analytical technique. Standardization of the entire
      workflow from test ordering to the report of the proteomic assay, with special
      emphasis on the preanalytical phase, is crucial for successful integration of
      proteomic studies in the clinic as protein profiles may change due to sample
      processing before the proteomic analysis is performed. The aim of this review is
      to discuss the progress of proteomic studies with human tissues and to highlight
      the challenges that must be understood and addressed for successful translation
      of proteomic methods to clinical practice.

PMID- 25580915
TI  - Cardiovascular and pulmonary adverse events in patients treated with BCR-ABL
      inhibitors: Data from the FDA Adverse Event Reporting System.
AB  - Rare but serious cardiovascular and pulmonary adverse events (AEs) have been
      reported in patients with chronic myeloid leukemia treated with BCR-ABL
      inhibitors. Clinical trial data may not reflect the full AE profile of BCR-ABL
      inhibitors because of stringent study entry criteria, relatively small sample
      size, and limited duration of follow-up. To determine the utility of the FDA AE
      Reporting System (FAERS) surveillance database for identifying AEs possibly
      associated with the BCR-ABL inhibitors imatinib, dasatinib, and nilotinib in the
      postmarketing patient population, we conducted Multi-Item Gamma Poisson Shrinker
      disproportionality analyses of FAERS reports on AEs in relevant system organ
      classes. Signals consistent with the known safety profiles of these agents as
      well as signals for less well-described AEs were detected. Bone marrow necrosis,
      conjunctival hemorrhage, and peritoneal fluid retention events were uniquely
      associated with imatinib. AEs that most commonly reached the threshold for
      dasatinib consisted of terms relating to hemorrhage and fluid retention,
      including pleural effusion and pericardial effusion. Most terms that reached the
      threshold solely with nilotinib were related to peripheral and cardiac vascular
      events. Although this type of analysis cannot determine AE incidence or establish
      causality, these findings elucidate the AEs reported in patients treated with BCR
      ABL inhibitors across multiple clinical trials and in the community setting for
      all approved and nonapproved indications, suggesting drug-AE associations warrant
      further investigation. These findings emphasize the need to consider patient
      comorbidities when selecting amongst BCR-ABL inhibitors.

PMID- 25580917
TI  - The relationship between symptomatic and functional changes of Korean children
      and adolescents with attention-deficit/hyperactivity disorder treated with
      osmotic-controlled release oral delivery system-methylphenidate.
AB  - OBJECTIVES: This study examined the effect of osmotic-controlled release oral
      delivery system-methylphenidate (OROS-MPH) on the adaptive functioning of
      children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and
      investigated the relationship between reduced ADHD symptoms and improvements in
      functioning and factors that are predictive of functional improvement. METHODS:
      This study was a prospective, multicenter, open-label study of 116 children with
      ADHD treated with OROS-MPH for 12 weeks. Attention-deficit/hyperactivity disorder
      symptoms, functional impairment, and other comorbid disorders were evaluated
      using various clinical scales. Correlational and multiple regression analyses
      were conducted to examine the relationship between symptomatic versus functional
      changes after OROS-MPH treatment. RESULTS: Correlation analysis showed a
      moderately strong association between changes in the ADHD core symptoms versus
      functional measure scores (r = -0.65). The self-control subscale of the Life
      Participation Scale showed higher correlations with symptomatic measures than did
      the happy/social subscale. Functional outcomes were impacted by several factors
      including the baseline severity of ADHD symptoms, changes in ADHD, and
      oppositional defiant symptoms after treatment. Attention was more associated with
      functional outcomes than hyperactivity/impulsivity. CONCLUSIONS: Treatment with
      OROS-MPH was associated with symptomatic functional changes that were moderately
      correlated; therefore, symptomatic functional outcomes appear to be partially
      overlapped but distinct domains. Consequently, functional measures should be
      incorporated as important outcome measures in future treatment studies; the
      importance of treatments targeting functional improvement should be emphasized in
      the treatment of children with ADHD.

PMID- 25580916
TI  - N-acetylcysteine as an adjunctive therapy to risperidone for treatment of
      irritability in autism: a randomized, double-blind, placebo-controlled clinical
      trial of efficacy and safety.
AB  - OBJECTIVES: According to the proposed interference of N-acetylcysteine (NAC) with
      pathophysiologic processes of autistic disorders (ADs), we aimed to assess the
      effectiveness and safety of NAC as an adjunct to risperidone in the treatment of
      ADs in a randomized, double-blind, clinical trial. METHODS: The participants were
      referred outpatients between 4 and 12 years of age with the diagnosis of ADs and
      a score of more than 12 on Aberrant Behavior Checklist-Community (ABC-C)
      Irritability subscale score. The participants were randomized into 2 groups. One
      group received risperidone plus NAC, and the other group received risperidone
      plus placebo. The dose of risperidone was titrated between 1 and 2.0 mg/d, and
      the dose of NAC was 600 to 900 mg/d. The main outcome was mean decrease in the
      ABC-C irritability subscale score from baseline at 5 and 10 weeks. Changes in
      other subscales were considered as secondary outcome measures. RESULTS: Forty
      patients completed the 10-week trial. Baseline characteristics including age, sex
      and body weight, as well as baseline scores in 5 subscales did not demonstrate
      statistically significant difference between the 2 groups. Repeated-measures
      analysis showed significant effect for time * treatment interaction in
      irritability (P = 0.01) and hyperactivity/noncompliance (P = 0.02) subscales. By
      week 10, the NAC group showed significantly more reduction in irritability (P =
      0.02) and hyperactivity/noncompliance (P = 0.01) subscales scores. CONCLUSIONS: N
      acetylcysteine can be considered as an adjuvant therapy for ADs with beneficial
      therapeutic outcomes.

PMID- 25580919
TI  - Fasting serum levels of neuropeptide y in patients with schizophrenia on
      clozapine monotherapy.
AB  - OBJECTIVE: Neuropeptide Y (NPY) is one of the hypothalamic hormones that works by
      increasing appetite and decreasing metabolism, leading to weight gain. We checked
      whether NPY level in subjects with schizophrenia on clozapine is higher compared
      with healthy controls. METHODS: We determined the fasting NPY levels of 24
      subjects with schizophrenia on clozapine monotherapy and 24 age- and sex-matched
      healthy controls. RESULTS: There was no difference for NPY between the clozapine
      group and the control group (mean [SD], 323.33 [138.50] vs 295.83 [25.28] pg/mL,
      P = 0.25). Neuropeptide Y was higher in women in the clozapine group (376.00
      [162.15] vs 275.45 [96.99] pg/mL, P = 0.048) but not in the control group (P =
      0.31) or in the whole study group (P = 0.20). We found no correlations between
      NPY and age, weight, body mass index, fat mass index, body circumferences, blood
      pressure, waist-to-hip ratio, levels of cholesterol, high-density lipoproteins,
      low-density lipoproteins, triglycerides, uric acid, calcium, homocysteine,
      glucose, insulin, insulin resistance, treatment duration, dose of clozapine, body
      composition, or basal metabolic rate. CONCLUSIONS: We cannot conclude that
      treatment with clozapine is associated with increased level of NPY. We did not
      find previously described differences in NPY for obesity or associations between
      NPY and metabolic parameters.

PMID- 25580914
TI  - Ultrasound imaging beyond the vasculature with new generation contrast agents.
AB  - Current commercially available ultrasound contrast agents are gas-filled, lipid-
      or protein-stabilized microbubbles larger than 1 um in diameter. Because the
      signal generated by these agents is highly dependent on their size, small yet
      highly echogenic particles have been historically difficult to produce. This has
      limited the molecular imaging applications of ultrasound to the blood pool. In
      the area of cancer imaging, microbubble applications have been constrained to
      imaging molecular signatures of tumor vasculature and drug delivery enabled by
      ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated
      advancements in nanomedicine, ultrasound contrast agents, which are an order of
      magnitude smaller (100-500 nm) than their currently utilized counterparts, have
      been undergoing rapid development. These agents are poised to greatly expand the
      capabilities of ultrasound in the field of targeted cancer detection and therapy
      by taking advantage of the enhanced permeability and retention phenomenon of many
      tumors and can extravasate beyond the leaky tumor vasculature. Agent
      extravasation facilitates highly sensitive detection of cell surface or
      microenvironment biomarkers, which could advance early cancer detection.
      Likewise, when combined with appropriate therapeutic agents and ultrasound
      mediated deployment on demand, directly at the tumor site, these nanoparticles
      have been shown to contribute to improved therapeutic outcomes. Ultrasound's
      safety profile, broad accessibility and relatively low cost make it an ideal
      modality for the changing face of healthcare today. Aided by the multifaceted
      nano-sized contrast agents and targeted theranostic moieties described herein,
      ultrasound can considerably broaden its reach in future applications focused on
      the diagnosis and staging of cancer.

PMID- 25580918
TI  - Therapeutic drug monitoring of antiepileptic drugs in a tertiary care hospital in
      India.
AB  - INTRODUCTION: Therapeutic drug monitoring (TDM) helps to optimize the dose of
      antiepileptic drugs. Only limited information is available about the clinical
      utility of TDM of antiepileptic drugs in India. Hence, we aimed to study the
      clinical utility of antiepileptic TDM in a tertiary care hospital in India and to
      explore the association between the plasma drug levels and the occurrence of
      breakthrough seizures and drug toxicity. METHODS: All patients taking
      antiepileptic drugs for whom TDM was done from January 2008 to December 2010 were
      included in the study. All relevant information was obtained from patient medical
      records. Trough levels were measured for all drugs using chemiluminescence assay.
      Drug levels were interpreted as within, below, and above the reference range, as
      recommended by the International League Against Epilepsy guidelines. RESULTS: Of
      the 420 samples analyzed during this period, 396 samples were included in this
      study for analysis. The maximum number of requests was for phenytoin (50%)
      followed by valproic acid (26%). The most common indication for TDM was dosage
      adjustment (38%) followed by breakthrough seizures (34%). Among the 135 samples
      received with breakthrough seizures as indication, more than 50% had drug levels
      either within or above the reference range. Among the 62 samples referred with
      clinical symptoms of suspected toxicity, drug levels were above the reference
      range in only 52% of the samples. CONCLUSIONS: Therapeutic drug monitoring was
      found to be useful in practice, in tailoring drug dosage in accordance with the
      needs of individual patient, in distinguishing nonresponders from noncompliants,
      and in aiding in making critical decisions. However, the "reference range" of
      these antiepileptic drugs was not reliable in predicting the occurrence of
      breakthrough seizures and clinical symptoms of suspected drug toxicity.

PMID- 25580920
TI  - Effects of age on paroxetine efficacy in patients with major depressive disorder
      who do not exhibit an early response to treatment.
AB  - OBJECTIVES: We investigated the effects of age on the association between early
      and eventual responses to paroxetine treatment in patients with major depressive
      disorder (MDD). METHODS: Eighty-nine patients with MDD were administered
      paroxetine and completed the 6-week protocol. On the basis of our previous study,
      we defined early responders as those patients with the Montgomery-Asberg
      Depression Rating Scale (MADRS) improvements higher than 35% at 2 weeks and
      responders as those patients with MADRS improvements higher than 50% at 6 weeks.
      The participants were divided into 4 groups in accordance with their responses:
      early response responders, early response nonresponders, nonearly response
      responders (NER-Rs), and nonearly response nonresponders (NER-NRs). Demographic
      data and the MADRS scores between the early response responders and the early
      response nonresponders and between the NER-Rs and the NER-NRs were compared. We
      used a receiver operating characteristic (ROC) curve to analyze age to determine
      the cutoff points for distinguishing responders and nonresponders in early and
      nonearly responders. RESULTS: There was a significant difference in age between
      the NER-Rs and the NER-NRs, with the NER-Rs being younger than the NER-NRs. The
      threshold for the response in the early responders was 42 years old. The area
      under the curve of the ROC curve of the early responders was 0.548. The threshold
      for the response of the nonearly responders was 55 years old. The area under the
      curve of the ROC curve of the early responders was 0.733. CONCLUSIONS: The
      effects of age on the association between the responsiveness in the early phase
      of antidepressant treatment and the eventual response were identified in patients
      with MDD.

PMID- 25580921
TI  - Quetiapine and clarithromycin-induced neuroleptic malignant syndrome.
AB  - We report a case of neuroleptic malignant syndrome possibly caused by the
      combined administration of quetiapine and clarithromycin in a 75-year-old male
      patient. He was receiving quetiapine regularly. Two days before his admission to
      the hospital, he had been feverish and started receiving clarithromycin without
      consulting a doctor. Clarithromycin administration was interrupted 3 days after
      his admission because it was ineffective and because his clinical state was
      deteriorating. The patient presented altered level of consciousness and excessive
      muscular rigidity on his limbs, while he remained feverish (38.7  degrees C).
      Laboratory abnormalities included elevated serum creatine phosphokinase level
      (5.387 U/L), leukocytosis, and low serum iron. The patient was diagnosed with
      neuroleptic malignant syndrome, and quetiapine was immediately discontinued.
      After the following days, his muscle rigidity and mental status ameliorated, his
      fever withdrew, and his laboratory findings improved. The various features of the
      case are discussed in view of the fact that the concomitant administration of
      cytochrome 3A4 inhibitors, such as clarithromycin, is suggested to cause an
      increase of plasma concentrations of quetiapine. Thus, physicians should have a
      high index of suspicion of the interactions of commonly administered medications.

PMID- 25580922
TI  - Hyperthyroid rage: when bipolar disorder hides the real disorder.
AB  - Long-term lithium therapy has been associated with euthyroid goiter,
      hypothyroidism, and less commonly, hyperthyroidism. We report a case of a 19-year
      old male patient with schizoaffective disorder who was hospitalized after trying
      to suffocate his mother. Severe psychomotor agitation persisted despite the high
      dose of antipsychotics. Initial laboratory tests showed elevated creatine kinase
      and free thyroxine. Lithium was replaced by sodium valproate, and new laboratory
      tests were obtained. After lithium discontinuation, the patient had a rapid
      improvement in agitation and tremors. Antithyroid drugs were not necessary,
      suggesting the diagnosis of lithium-associated thyrotoxicosis that progressed to
      spontaneous remission. There are only 2 other reports of lithium-associated
      thyrotoxicosis successfully treated with lithium withdrawal. Even patients on
      long-term use of lithium are not free from having acute thyroid dysfunction and
      may present with treatment-resistant symptoms. 

PMID- 25580923
TI  - Amisulpride as add-on treatment for resistant obsessive-compulsive disorder:
      retrospective case series.
AB  - Obsessive-compulsive disorder (OCD) is one of the most common and disabling
      psychiatric disorders. Treatment with selective serotonin reuptake inhibitors
      (SSRIs) shows significant improvement; however, residual symptoms remain in most
      patients despite continued treatment. For partial or nonresponding patients to
      multiple SSRIs, augmentation strategies are usually recommended. Here we present
      a consecutive sample of patients with resistant OCD treated with amisulpride
      augmentation to SSRIs. METHODS: We present 10 patients (5 males, 5 females)
      experiencing resistant OCD. Subjects were treated openly for 6 weeks with
      amisulpride 200 mg/d as add-on, excluding 1 patient who was treated with only 100
      mg/d due to acute extrapyramidal adverse effect on a larger dose. Efficacy was
      assessed at baseline and after 6 weeks of treatment using the Yale-Brown
      Obsessive-Compulsive Scale, Clinical Global Impression-Severity, and Clinical
      Global Impression-Improvement. RESULTS: The treatment was generally well
      tolerated without serious events. In all patients, average Yale-Brown Obsessive
      Compulsive Scale scores diminished from 25.3 +/- 5.96 points at baseline to 12.2
      +/- 5.98 at the sixth week (P < 0.0005). Of 10 patients, 7 had significant and
      partial improvement, and 3 patients did not demonstrate any improvement.
      CONCLUSIONS: Treatment-resistant OCD patients positively responded and well
      tolerated amisulpride add-on to their ongoing regular pharmacotherapy. This case
      series demonstrates that amisulpride could be a promising optional therapy for
      patients who have resistant OCD. Further randomized controlled studies are
      necessary.

PMID- 25580924
TI  - Tetrabenazine for tardive tremor in elderly adults: a prospective follow-up
      study.
AB  - Tardive tremor (TT) is a rare neuroleptic-induced tardive syndrome. It is mainly
      postural and action associated rather than resting tremor without other
      parkinsonian features and resistant to most therapeutic interventions.
      Tetrabenazine (TBZ) is a possible option for treating TT.This study aimed to
      evaluate the efficacy and tolerability of TBZ in elderly patients with TT.
      Patients (N = 10) received TBZ (25-150 mg/d) for 6 weeks. Five subjects completed
      the study. Mean TBZ dose at study end was 57.5 +/- 37.3 mg/d. Mean Abnormal
      Involuntary Movement score was 13.3 +/- 6.6, mean Tremor Scale score was 2.3 +/-
      0.9, mean Clinical Global Impression-Change was 3.6 +/- 2.2, and mean Geriatric
      Depression Score was 5.2 +/- 4.9; all not significantly changed from baseline.
      Five patients suffered side effects, including depression (n = 3), parkinsonism
      (n = 2), akathisia (n = 1), and mild stroke (n = 1).This prospective study does
      not support TBZ treatment for TT in elderly psychiatric patients. 

PMID- 25580925
TI  - Oral human papillomavirus infection in men who have sex with men with anal
      squamous intraepithelial lesions.
AB  - BACKGROUND: Little is known about the association between oral and anogenital
      human papillomavirus (HPV) infections. METHODS: Oral and anal samples from 66 men
      who have sex with men with a history of HPV-related anogenital squamous
      intraepithelial lesions were analyzed using polymerase chain reaction (PCR), and
      typed for 38 HPV types. RESULTS: Prevalence of oral HPV infection was 30%, versus
      82% for anal infection. Prevalence of oral and anal high-risk HPV infection was
      11% and 64%, respectively. Concurrent oral-anal any-type HPV infection was found
      in 26% of participants, whereas concordant type-specific HPV prevalence was 5%.
      In multivariate analysis, number of partners from whom the participant received
      oral-penile sex and number of partners on whom the participant performed oral
      penile sex were associated with oral HPV infection. CONCLUSION: Oral HPV
      prevalence in this cohort is high, however, concordant type-specific oral-anal
      HPV infection was rare. Increased risk of oral HPV infection was associated with
      oral-penile sex. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E399-E405, 2016.

PMID- 25580926
TI  - Controlled doping of large-area trilayer MoS2 with molecular reductants and
      oxidants.
AB  - Highly uniform large-area MoS2 is chemically doped using molecular reductants and
      oxidants. Electrical measurements, photoemission, and Raman spectroscopy are used
      to study the doping effect and to understand the underlying mechanism. Strong
      work-function changes of up to +/-1 eV can be achieved, with contributions from
      state filling and surface dipoles. This results in high doping densities of up to
      ca. 8 * 10(12) cm(-2) . 

PMID- 25580927
TI  - Extended pi-conjugated ruthenium zinc-porphyrin complexes with enhanced nonlinear
      optical properties.
AB  - Zinc porphyrin dimers and trimers, in which the porphyrins are connected via a
      ruthenium metal core, exhibit large third-order nonlinear optical absorption
      coefficients and refractive indices. These properties are a result of the
      presence of multiple porphyrins, which lead to an extension of the pi-conjugated
      system and the octupolar effect. 

PMID- 25580928
TI  - Testing the limits of resistance: a 19-year study of Mediterranean grassland
      response to grazing regimes.
AB  - A synthesis of a long-term (19 years) study assessing the effects of cattle
      grazing on the structure and composition of a Mediterranean grassland in north
      eastern Israel is presented, with new insights into the response of the
      vegetation to grazing management and rainfall. We hypothesized that the plant
      community studied would be resistant to high grazing intensities and rainfall
      variability considering the combined long history of land-use and unpredictable
      climatic conditions where this community evolved. Treatments included
      manipulations of stocking densities (moderate, heavy, and very heavy) and of
      grazing regimes (continuous vs. seasonal), in a factorial design. The effect of
      interannual rainfall variation on the expression of grazing impacts on the plant
      community was minor. The main effects of grazing on relative cover of plant
      functional groups were related to early vs. late seasonal grazing. Species
      diversity and equitability were remarkably stable across all grazing treatments.
      A reduction in tall grass cover at higher stocking densities was correlated with
      increased cover of less palatable groups such as annual and perennial thistles,
      as well as shorter and prostrate groups such as short annual grasses. This long
      term study shows that interannual fluctuations in plant functional group
      composition could be partly accounted for by grazing pressure and timing, but not
      by the measured rainfall variables. Grazing affected the dominance of tall annual
      grasses. However, the persistence of tall grasses and more palatable species over
      time, despite large differences in grazing pressure and timing, supports the idea
      that Mediterranean grasslands are highly resistant to prolonged grazing. Indeed,
      even under the most extreme grazing conditions applied, there were no signs of
      deterioration or collapse of the ecosystem. This high resistance to grazing
      intensity and interannual fluctuation in climatic conditions should favor the
      persistence of the plant community under forecasted increasing unpredictability
      due to climate change.

PMID- 25580929
TI  - Identification and partial characterization of proteases in larval preparations
      of the cereal leaf beetle (Oulema melanopus, Chrysomelidae, Coleoptera).
AB  - We determined some biochemical properties of Oulema melanopus larval gut
      proteases. We found adult midgut enzyme preparations yielded results similar to
      whole-larval preparations, permitting studies of the very small whole-larval
      preparations. Protein preparations were analyzed using FITC-casein as a
      substrate. Acidic pH is optimal for proteolytic activity (range 3.0-4.0).
      Cysteine protease activity increased at acidic pH and in the presence of beta
      mercaptoethanol. Protease activities at all pH values were maximal at 45 degrees
      C. Enzyme activity in larval preparations was inhibited by addition of Fe(2+) ,
      Ca(2+) , Mg(2+) , Zn(2+) , and K(+) (10 mM). Fe(2+) and Zn(2+) significantly
      decreased enzyme activity at all pH values, Ca(2+) and Mg(2+) at pH 6.2 and
      Mg(2+) at pH 4.0. Inhibitors, including pepstatin A, showed the greatest
      inhibition at pH 4.0; phenylmethylsulfonyl fluoride, N-p-tosyl-l-phenylalanine
      chloromethyl ketone at pH 6.2; and phenylmethylsulfonyl fluoride, Nalpha -tosyl-l
      lysine chloromethyl ketone hydrochloride, N-p-tosyl-l-phenylalanine chloromethyl
      ketone, trans-epoxysuccinyl-l-leucylamido-(4-guanidino) butane at pH of 7.6.
      Inhibition assays indicated that cysteine, aspartyl (cathepsin D), serine
      (trypsin, chymotrypsin-like) proteases and metalloproteases act in cereal leaf
      beetle digestion.

PMID- 25580930
TI  - Theoretical and experimental research on the self-assembled system of molecularly
      imprinted polymers formed by salbutamol and methacrylic acid.
AB  - The quantum chemical method was applied for screening functional monomers in the
      rational design of salbutamol-imprinted polymers. Salbutamol was the template
      molecule, and methacrylic acid was the single functional monomer. The LC-WPBE/6
      31G(d,p) method was used to investigate the geometry optimization, active sites,
      natural bond orbital charges, binding energies of the imprinted molecule, and
      solvation energy. The mechanism of action between salbutamol and methacrylic acid
      was also discussed. The theoretical results show that salbutamol interacts with
      functional monomers by hydrogen bonds, and the salbutamol-imprinted polymers with
      a ratio of 1:4 (salbutamol/methacrylic acid) in acetonitrile had the highest
      stability. The salbutamol-imprinted polymers were prepared by precipitation
      polymerization. The experimental results indicated that the maximum adsorption
      capacity for salbutamol toward molecularly imprinted polymers was 7.33 mg/g, and
      the molecularly imprinted polymers had a higher selectivity for salbutamol than
      for norepinephrine and terbutaline sulfate. Herein, the studies can provide
      theoretical and experimental references for the salbutamol molecular imprinted
      system. 

PMID- 25580931
TI  - This Ad is for You: Targeting and the Effect of Alcohol Advertising on Youth
      Drinking.
AB  - Endogenous targeting of alcohol advertisements presents a challenge for
      empirically identifying a causal effect of advertising on drinking. Drinkers
      prefer a particular media; firms recognize this and target alcohol advertising at
      these media. This paper overcomes this challenge by utilizing novel data with
      detailed individual measures of media viewing and alcohol consumption and three
      separate empirical techniques, which represent significant improvements over
      previous methods. First, controls for the average audience characteristics of the
      media an individual views account for attributes of magazines and television
      programs alcohol firms may consider when deciding where to target advertising. A
      second specification directly controls for each television program and magazine a
      person views. The third method exploits variation in advertising exposure due to
      a 2003 change in an industry-wide rule that governs where firms may advertise.
      Although the unconditional correlation between advertising and drinking by youth
      (ages 18-24) is strong, models that include simple controls for targeting imply,
      at most, a modest advertising effect. Although the coefficients are estimated
      less precisely, estimates with models including more rigorous controls for
      targeting indicate no significant effect of advertising on youth drinking.

PMID- 25580932
TI  - The ugly truth: negative gossip about celebrities and positive gossip about self
      entertain people in different ways.
AB  - In contrast to abstract trait words which describe people's general personality,
      gossip is about personal affairs of others. Although neural correlates underlying
      processing self-related trait words have been well documented, it remains poorly
      understood how the human brain processes gossip. In the present fMRI study,
      participants were instructed to rate their online emotional states upon hearing
      positive and negative gossip about celebrities, themselves, and their best
      friends. Explicit behavioral ratings suggested that participants were happier to
      hear positive gossip and more annoyed to hear negative gossip about themselves
      than about celebrities and best friends. At the neural level, dissociated neural
      networks were involved in processing the positive gossip about self and the
      negative gossip about celebrities. On the one hand, the superior medial
      prefrontal cortex responded not only to self-related gossip but also to moral
      transgressions, and neural activity in the orbital prefrontal cortex increased
      linearly with pleasure ratings on positive gossip about self. On the other hand,
      although participants' ratings did not show they were particularly happy on
      hearing negative gossip about celebrities, the significantly enhanced neural
      activity in the reward system suggested that they were indeed amused. Moreover,
      via enhanced functional connectivity, the prefrontal executive control network
      was involved in regulating the reward system by giving explicit pleasure ratings
      according to social norm compliance, rather than natural true feelings. 

PMID- 25580934
TI  - Phycoremediation of Tannery Wastewater Using Microalgae Scenedesmus Species.
AB  - A number of microalgae species are efficient in removing toxicants from
      wastewater. Many of these potential species are a promising, eco-friendly, and
      sustainable option for tertiary wastewater treatment with a possible advantage of
      improving the economics of microalgae cultivation for biofuel production. The
      present study deals with the phycoremediation of tannery wastewater (TWW) using
      Scenedesmus sp. isolated from a local habitat. The test species was grown in TWW
      under laboratory conditions and harvested on the 12th day. The results revealed
      that the algal biomass during the growth period not only reduced the pollution
      load of heavy metals (Cr-81.2-96%, Cu-73.2-98%, Pb-75-98% and Zn-65-98%) but also
      the nutrients (NO3 >44.3% and PO4 >95%). Fourier Transform Infrared (FTIR)
      spectrums of Scenedesmus sp. biomass revealed the involvement of hydroxyl amino,
      carboxylic and carbonyl groups. The scanning electron micrograph (SEM) and Energy
      Dispersive X-ray Spectroscopic analysis (EDS) revealed the surface texture,
      morphology and element distribution of the biosorbent. Furthermore, the
      wastewater generated during wet-blue tanning process can support dense population
      of Scenedesmus sp., making it a potential growth medium for biomass production of
      the test alga for phycoremediation of toxicants in tannery wastewaters.

PMID- 25580935
TI  - Letter from the editor.

PMID- 25580933
TI  - Comorbidities and race/ethnicity among adults with stimulant use disorders in
      residential treatment.
AB  - Comorbid physical and mental health problems are associated with poorer substance
      abuse treatment outcomes; however, little is known about these conditions among
      stimulant abusers at treatment entry. This study compared racial and ethnic
      groups on baseline measures of drug use patterns, comorbid physical and mental
      health disorders, quality of life, and daily functioning among cocaine and
      stimulant abusing/dependent patients. Baseline data from a multi-site randomized
      clinical trial of vigorous exercise as a treatment strategy for a diverse
      population of stimulant abusers (N=290) were analyzed. Significant differences
      between groups were found on drug use characteristics, stimulant use disorders,
      and comorbid mental and physical health conditions. Findings highlight the
      importance of integrating health and mental health services into substance abuse
      treatment and could help identify potential areas for intervention to improve
      treatment outcomes for racial and ethnic minority groups.

PMID- 25580936
TI  - Interfacial-strain-induced structural and polarization evolutions in epitaxial
      multiferroic BiFeO3 (001) thin films.
AB  - Varying the film thickness is a precise route to tune the interfacial strain to
      manipulate the properties of the multiferroic materials. Here, to explore the
      effects of the interfacial strain on the properties of the multiferroic BiFeO3
      films, we investigated thickness-dependent structural and polarization evolutions
      of the BiFeO3 films. The epitaxial growth with an atomic stacking sequence of
      BiO/TiO2 at the interface was confirmed by scanning transmission electron
      microscopy. Combining X-ray diffraction experiments and first-principles
      calculations, a thickness-dependent structural evolution was observed from a
      fully strained tetragonality to a partially relaxed one without any structural
      phase transition or rotated twins. The tetragonality (c/a) of the BiFeO3 films
      increases as the film thickness decreases, while the polarization is in contrast
      with this trend, and the size effect including the depolarization field plays a
      crucial role in this contradiction in thinner films. These findings offer an
      alternative strategy to manipulate structural and polarization properties by
      tuning the interfacial strain in epitaxial multiferroic thin films. 

PMID- 25580937
TI  - An Update on Evidence-Based Psychosocial Treatments for Eating Disorders in
      Children and Adolescents.
AB  - Eating disorders are relatively common and serious disorders in adolescents.
      However, there are few controlled psychosocial intervention studies with this
      younger population. This review updates a previous Journal of Clinical Child and
      Adolescent Psychology review published in 2008. The recommendations in this
      review were developed after searching the literature including PubMed/Medline and
      employing the relevant medical subject headings. In addition, the bibliographies
      of book chapters and treatment guideline articles were reviewed; last, colleagues
      were asked for suggested additional source materials. Psychosocial treatments
      examined include family therapy, individual therapy, cognitive behavioral
      therapy, interpersonal psychotherapy, cognitive training, and dialectical
      behavior therapy. Using the most recent Journal of Clinical Child and Adolescent
      Psychology methodological review criteria, family treatment-behavior (FT-B) is
      the only well-established treatment for adolescents with anorexia nervosa. Family
      treatment-systemic and insight oriented individual psychotherapy are probably
      efficacious treatments for adolescents with anorexia nervosa. There are no well
      established treatments for adolescents with bulimia nervosa, binge eating
      disorder, or avoidant restrictive food intake disorder. Possibly efficacious
      psychosocial treatments for adolescent bulimia nervosa include FT-B and
      supportive individual therapy. Internet-delivered cognitive behavioral therapy is
      a possibly efficacious treatment for binge eating disorder. Experimental
      treatments for adolescent eating disorders include enhanced cognitive behavioral
      therapy, dialectical behavioral therapy, cognitive training, and interpersonal
      psychotherapy. FT-B is the only well-established treatment for adolescent eating
      disorders. Additional research examining treatment for eating disorders in youth
      is warranted. 

PMID- 25580938
TI  - Amount and type of everyday technology use over time in older adults with
      cognitive impairment.
AB  - OBJECTIVES: This two-year study examined everyday technology (ET) use in older
      adults with mild cognitive impairment (MCI) testing five predefined theoretical
      assumptions regarding factors potentially influencing the amount of ET used in
      everyday life. METHODS: Data from 37 participants with MCI were collected at
      inclusion, six, 12, and 24 months, on the type and amount of ET used and how
      difficult this was, activity involvement, and cognitive and diagnostic status.
      These variables were, together with age group (55-64, 65-74, or 75-84 years) and
      educational level, analysed in a mixed-linear-effect model. RESULTS: A
      significant decrease in the overall amount of ET used was found over time, but
      the number of users of specific ETs both decreased and increased. Increasing
      perceived difficulty in ET use, less activity involvement, decreasing cognitive
      status, and belonging to the oldest age group significantly decreased ET use. Two
      years after inclusion 42% of the participants had converted to dementia, but
      neither change in diagnostic status nor length of education contributed
      significantly to the predictive model. CONCLUSION: Over time, a decreasing use of
      ET was shown in this sample with MCI. This process was influenced by several
      aspects important to consider in occupational therapy intervention planning.

PMID- 25580939
TI  - Reading Level and Length of Written Research Consent Forms.
AB  - In 100 Institutional Review Board approved consent forms (CFs), we assessed
      pages, reading levels, and whether they included essential elements. CF page
      numbers ranged from 3 to 28 (mean, 10.3) and readability ranged from grades 5.6
      to 28.9 (mean, 11.6). The CF mean score for including essential elements was
      90.8% (range: 63.5-100%). There were no significant differences by specialty in
      number of pages (p = 0.053), but surgical specialties had the highest readability
      (mean, 13.1), and pediatrics the lowest (10.5), p = 0.008. While approved CFs
      generally included the Office for Human Research Protections recommended
      essential elements, they were very long, and even pediatric forms, which had the
      lowest reading levels, were written on average at a tenth grade level.
      Researchers need guidance to resolve pressure between regulatory mandates and
      guidelines and "keeping it simple and clear." 

PMID- 25580940
TI  - Targeted deletion of regulatory T cells attenuates the protective effects of
      myocardial ischemic preconditioning in rats.
AB  - BACKGROUND: Myocardial ischemia-reperfusion injury (IRI) is associated with
      activation of the innate immune system and the resultant inflammatory response.
      Myocardial ischemic preconditioning (IPC) is the most powerful endogenous
      protective mechanism against myocardial IRI, probably via the role of anti
      inflammation. Regulatory T cells (Tregs), which are characterized by the
      expression of the forkhead/winged-helix transcription factor FoxP3, play an
      important role in the negative modulation of immune responses. We tested the
      hypothesis that Tregs may contribute to the protective effect of myocardial IPC
      through anti-inflammatory mechanisms. METHODS AND RESULTS: The left anterior
      descending coronary arteries of rats were occluded for a 30-min ischemia,
      followed by a 48-h reperfusion. Myocardial IPC was induced by 4 cycles of 5-min
      ischemia and 5-min reperfusion. Ischemia was achieved by ligation of the left
      anterior descending coronary artery (LAD), and reperfusion was initiated by
      releasing the ligature. Rats were injected with a Treg cell-depleting antibody or
      normal rat immunoglobulin (IgG), after IPC. The accumulation of Tregs was
      observed at indexed time points following IPC. The protein expression of FoxP3
      significantly increased in the myocardium after IPC, and peaked at day-2.
      Treatment of preconditioned rats with the Treg cell-depleting antibody
      demonstrated less protein expression of FoxP3 (p < 0.001), more infiltration of
      inflammatory cells in the myocardium (p < 0.01), and larger myocardial infarct
      size (p < 0.001), compared with the IgG injection group. CONCLUSION:
      Cardioprotection by IPC is associated with Tregs.

PMID- 25580941
TI  - Physician self-referral: regulation by exceptions.

PMID- 25580942
TI  - Advantages and limitations of teleneurology.
AB  - IMPORTANCE: The growing disparity between the demand for neurological services
      and the need for neurologists requires new and innovative strategies for
      delivering care. Teleneurology allows neurological expertise to be delivered to
      remote locations to supplement or replace in-person neurological care. OBJECTIVE:
      To summarize the current status of teleneurology. Applications of teleneurology
      include acute care, outpatient teleneurology, and teleconsultations. Existing
      barriers to further expansion of teleneurology are also discussed. EVIDENCE
      REVIEW: Published studies pertaining to teleneurology were reviewed. Practical
      experience with telemedicine in neurological practice contributed to the
      conclusions. FINDINGS: Outcomes after intravenous tissue plasminogen activator
      treatment via telemedicine (telestroke) are similar to those achieved with in
      person evaluations. Other aspects of teleneurology are less established but have
      demonstrated feasibility, high patient satisfaction, and, in some cases, cost
      savings. CONCLUSIONS AND RELEVANCE: Teleneurology provides neurological expertise
      to rural areas with limited availability of neurologists and improves care for
      patients with difficulty traveling owing to neurological disease. It is likely
      that use of teleneurology will continue to grow and become incorporated into many
      aspects of neurological practice. Understanding the advantages and limitations of
      teleneurology is vital to delivering optimal clinical care for patients with
      neurological disease regardless of the setting.

PMID- 25580943
TI  - Unilateral hydronephrosis and urosepsis secondary to vaginal ring pessary.

PMID- 25580944
TI  - Mycotoxin production capability of Penicillium roqueforti in strains isolated
      from mould-ripened traditional Turkish civil cheese.
AB  - Mould-ripened civil is a traditional cheese produced mainly in eastern Turkey.
      The cheese is produced with a mixture of civil and whey curd cheeses (lor). This
      mixture is pressed into goat skins or plastic bags and is ripened for more than
      three months. Naturally occurring moulds grow on the surface and inside of the
      cheese during ripening. In this research, 140 Penicillium roqueforti strains were
      isolated from 41 samples of mould-ripened civil cheese collected from Erzurum and
      around towns in eastern Turkey. All strains were capable of mycotoxin production
      and were analysed using an HPLC method. It was established that all the strains
      (albeit at very low levels) produced roquefortine C, penicillic acid,
      mycophenolic acid and patulin. The amounts of toxins were in the ranges 0.4-47.0,
      0.2-43.6, 0.1-23.1 and 0.1-2.3 mg kg(-1), respectively. Patulin levels of the
      samples were lower than the others. The lowest level and highest total mycotoxin
      levels were determined as 1.2 and 70.1 mg kg(-1) respectively. The results of
      this preliminary study may help in the choice of secondary cultures for mould
      ripened civil cheese and other mould-ripened cheeses.

PMID- 25580945
TI  - Hospital volume and cardiac complications of endomyocardial biopsy: a
      retrospective cohort study of 9508 adult patients using a nationwide inpatient
      database in Japan.
AB  - BACKGROUND: Recent research on complications with endomyocardial biopsy (EMB) has
      been based on single-center or 2-center studies in high-volume cardiovascular
      centers. No study has examined the association between hospital volume and the
      complication rate after EMB. HYPOTHESIS: Hospital volume is inversely associated
      with cardiac complication rate after EMB. METHODS: Using the Diagnosis Procedure
      Combination database in Japan, we identified inpatients aged >=20 years who
      underwent EMB under fluoroscopic guidance. We assessed cardiac complications
      requiring the following urgent procedures on the day of EMB or the day after:
      pericardiocentesis, surgical repair, and temporary pacing. RESULTS: Among 9508
      eligible patients in 491 hospitals (male, 68%; mean age, 57.0 years), dilated
      cardiomyopathy was the most frequently diagnosed condition (35.4%). Twenty-four
      patients (0.25%) required pericardiocentesis on the day of EMB. Three patients
      (0.03%) underwent surgical repair on the day of EMB or the day after. Sixty-three
      patients (0.70%) required temporary pacing on the day of EMB. Higher hospital
      volume was associated with lower rates of pericardiocentesis (low volume, 0.4%;
      medium volume, 0.2%; high volume, 0.1%; P for the trend test, 0.019) and
      temporary pacing (low volume, 1.0%; medium volume, 0.7%; high volume, 0.2%; P for
      the trend test, < 0.001). In a multivariable logistic regression analysis, high
      hospital volume was significantly associated with a lower rate of the composite
      outcome of the procedures (reference, low volume; adjusted odds ratio, 0.22; 95%
      confidence interval, 0.08-0.62, P = 0.004). CONCLUSIONS: Serious cardiac
      complications of EMB were rare, but higher hospital volume was associated with
      lower complication rate.

PMID- 25580947
TI  - Thresholds of species loss in Amazonian deforestation frontier landscapes.
AB  - In the Brazilian Amazon, private land accounts for the majority of remaining
      native vegetation. Understanding how land-use change affects the composition and
      distribution of biodiversity in farmlands is critical for improving conservation
      strategies in the face of rapid agricultural expansion. Working across an area
      exceeding 3 million ha in the southwestern state of Rondonia, we assessed how the
      extent and configuration of remnant forest in replicate 10,000-ha landscapes has
      affected the occurrence of a suite of Amazonian mammals and birds. In each of 31
      landscapes, we used field sampling and semistructured interviews with landowners
      to determine the presence of 28 large and medium sized mammals and birds, as well
      as a further 7 understory birds. We then combined results of field surveys and
      interviews with a probabilistic model of deforestation. We found strong evidence
      for a threshold response of sampled biodiversity to landscape level forest cover;
      landscapes with <30-40% forest cover hosted markedly fewer species. Results from
      field surveys and interviews yielded similar thresholds. These results imply that
      in partially deforested landscapes many species are susceptible to extirpation
      following relatively small additional reductions in forest area. In the model of
      deforestation by 2030 the number of 10,000-ha landscapes under a conservative
      threshold of 43% forest cover almost doubled, such that only 22% of landscapes
      would likely to be able to sustain at least 75% of the 35 focal species we
      sampled. Brazilian law requires rural property owners in the Amazon to retain 80%
      forest cover, although this is rarely achieved. Prioritizing efforts to ensure
      that entire landscapes, rather than individual farms, retain at least 50% forest
      cover may help safeguard native biodiversity in private forest reserves in the
      Amazon.

PMID- 25580946
TI  - Integrative population pharmacokinetic and pharmacodynamic dose finding approach
      of the new camptothecin compound namitecan (ST1968).
AB  - AIMS: Namitecan is a new camptothecan compound undergoing early clinical
      development. This study was initiated to build an integrated pharmacokinetic (PK)
      and pharmacodynamic (PD) population model of namitecan to guide future clinical
      development. METHODS: Plasma concentration-time data, neutrophils and
      thrombocytes were pooled from two phase 1 studies in 90 patients with advanced
      solid tumours, receiving namitecan as a 2 h infusion on days 1 and 8 every 3
      weeks (D1,8) (n = 34), once every 3 weeks (D1) (n = 29) and on 3 consecutive days
      (D1-3) (n = 27). A linear three compartment PK model was coupled to a
      semiphysiological PD-model for neutrophils and thrombocytes. Data simulations
      were used to interrogate various dosing regimens and give dosing recommendations.
      RESULTS: Clearance was estimated to be 0.15 l h(-1), with a long terminal half
      life of 48 h. Body surface area was not associated with clearance, supporting
      flat-dosing of namitecan. A significant and clinically relevant association was
      found between namitecan area under the concentration-time curve (AUC) and the
      percentage drop of neutrophils (r(2) = 0.51, P < 10(-4)) or thrombocytes (r(2) =
      0.49, P < 10(-4)). With a target for haematological dose-limiting toxicity of
      <20%, the recommended dose was defined as 12.5 mg for the D1,8 regimen, 23 mg for
      the once every 3 week regimen and 7 mg for the D1-3 regimen. CONCLUSION: This is
      the first integrated population PK-PD analysis of the new hydrophilic
      topoisomerase I inhibitor namitecan, that is currently undergoing early clinical
      development. A distinct relationship was found between drug exposure and
      haematological toxicity, supporting flat-dosing once every 3 weeks as the most
      adequate dosing regimen.

PMID- 25580948
TI  - Optimal numbers of matings: the conditional balance between benefits and costs of
      mating for females of a nuptial gift-giving spider.
AB  - In species where females gain a nutritious nuptial gift during mating, the
      balance between benefits and costs of mating may depend on access to food. This
      means that there is not one optimal number of matings for the female but a range
      of optimal mating numbers. With increasing food availability, the optimal number
      of matings for a female should vary from the number necessary only for
      fertilization of her eggs to the number needed also for producing these eggs. In
      three experimental series, the average number of matings for females of the
      nuptial gift-giving spider Pisaura mirabilis before egg sac construction varied
      from 2 to 16 with food-limited females generally accepting more matings than well
      fed females. Minimal level of optimal mating number for females at satiation
      feeding conditions was predicted to be 2-3; in an experimental test, the median
      number was 2 (range 0-4). Multiple mating gave benefits in terms of increased
      fecundity and increased egg hatching success up to the third mating, and it had
      costs in terms of reduced fecundity, reduced egg hatching success after the third
      mating, and lower offspring size. The level of polyandry seems to vary with the
      female optimum, regulated by a satiation-dependent resistance to mating,
      potentially leaving satiated females in lifelong virginity. 

PMID- 25580949
TI  - Germination sensitivities to water potential among co-existing C3 and C4 grasses
      of cool semi-arid prairie grasslands.
AB  - An untested theory states that C4 grass seeds could germinate under lower water
      potentials (Psi) than C3 grass seeds. We used hydrotime modelling to study seed
      water relations of C4 and C3 Canadian prairie grasses to address Psi divergent
      sensitivities and germination strategies along a risk-spreading continuum of
      responses to limited water. C4 grasses were Bouteloua gracilis, Calamovilfa
      longifolia and Schizachyrium scoparium; C3 grasses were Bromus carinatus, Elymus
      trachycaulus, Festuca hallii and Koeleria macrantha. Hydrotime parameters were
      obtained after incubation of non-dormant seeds under different Psi PEG 6000
      solutions. A t-test between C3 and C4 grasses did not find statistical
      differences in population mean base Psi (Psib (50)). We found idiosyncratic
      responses of C4 grasses along the risk-spreading continuum. B. gracilis showed a
      risk-taker strategy of a species able to quickly germinate in a dry soil due to
      its low Psib (50) and hydrotime (thetaH ). The high Psib (50) of S. scoparium
      indicates it follows the risk-averse strategy so it can only germinate in wet
      soils. C. longifolia showed an intermediate strategy: the lowest Psib (50) yet
      the highest thetaH . K. macrantha, a C3 grass which thrives in dry habitats, had
      the highest Psib (50), suggesting a risk-averse strategy for a C3 species. Other
      C3 species showed intermediate germination patterns in response to Psi relative
      to C4 species. Our results indicate that grasses display germination
      sensitivities to Psi across the risk-spreading continuum of responses. Thus seed
      water relations may be poor predictors to explain differential recruitment and
      distribution of C3 and C4 grasses in the Canadian prairies. 

PMID- 25580950
TI  - Dopamine transporter oligomerization: impact of combining protomers with
      differential cocaine analog binding affinities.
AB  - Previous studies point to quaternary assembly of dopamine transporters (DATs) in
      oligomers. However, it is not clear whether the protomers function independently
      in the oligomer. Is each protomer an entirely separate unit that takes up
      dopamine and is inhibited by drugs known to block DAT function? In this work,
      human embryonic kidney 293 cells were co-transfected with DAT constructs
      possessing differential binding affinities for the phenyltropane cocaine analog,
      [3H]WIN35,428. It was assessed whether the binding properties in co-expressing
      cells capable of forming hetero-oligomers differ from those in preparations
      obtained from mixed singly transfected cells where such oligomers cannot occur. A
      method is described that replaces laborious 'mixing' experiments with an in
      silico method predicting binding parameters from those observed for the singly
      expressed constructs. Among five pairs of constructs tested, statistically
      significant interactions were found between protomers of wild-type (WT) and
      D313N, WT and D345N, and WT and D436N. Compared with predicted Kd values of
      [3H]WIN35,428 binding to the non-interacting pairs, the observed affinity of the
      former pair was increased 1.7 fold while the latter two were reduced 2.2 and 4.1
      fold, respectively. This is the first report of an influence of protomer
      composition on the properties of a DAT inhibitor, indicating cooperativity within
      the oligomer. The dopamine transporter (DAT) can exist as an oligomer but it is
      unknown whether the protomers function independently. The present results
      indicate that protomers that are superpotent or deficient in cocaine analog
      binding can confer enhanced or reduced potency to the oligomer, respectively. In
      this respect, positive or negative cooperativity is revealed in the DAT oligomer.

PMID- 25580951
TI  - Sal-like protein 2 upregulates p16 expression through a proximal promoter
      element.
AB  - Sal-like protein 2 (Sall2), a homeotic transcription factor, is a putative tumor
      suppressor. We have previously shown that Sall2 activates the transcription of
      tumor suppressor gene p21 and suppresses tumorigenesis through cell cycle
      inhibition and induction of apoptosis. To investigate additional Sall2-regulated
      downstream genes, we analyzed the differences in mRNA expression profiles with
      and without exogenously expressed Sall2. We identified 1616 Sall2-responsive
      genes through gene expression arrays. Promoter-reporter assays of p16(INK4A) and
      several other tumor-related genes indicated that the Sall2 regulation of these
      promoters was not significantly different between the two major forms of Sall2
      with alternative exon 1 or exon 1A. Additional analysis showed that Sall2-induced
      p16 promoter activation was Sall2 dose-dependent. Deletion and site-directed
      mutagenesis of the p16 promoter identified a consensus Sall2 binding site
      (GGGTGGG) proximal to the p16 transcription start site and was critical for p16
      promoter activation. Finally, to confirm the significance of Sall2-activated p16
      expression in cell cycle regulation, we co-transfected the SKOV3 cells with a
      Sall2 expression construct and a p16 minigene and also co-transfected the ES-2
      cells with a Sall2 expression construct and the siRNA against p16 for flow
      cytometry analysis. Our results showed that Sall2 enhanced the p16 minigene
      blocking of cell cycle progression and p16 knockdown with siRNA abolished most of
      the Sall2 inhibition of cell cycle progression. These findings indicate that
      Sall2 targets multiple cell cycle regulators, including p16, through their
      promoters, adding knowledge to the understanding of Sall2 and p16 gene
      regulation, and how Sall2 deregulation may promote cancer formation.

PMID- 25580952
TI  - The NICU Parent Risk Evaluation and Engagement Model and Instrument (PREEMI) for
      neonates in intensive care units.
AB  - Engagement is a fairly new concept in practice and research and is gaining the
      interest of federal and private regulators, clinicians, and researchers. In this
      article, we offer a standard definition and outline an engagement model and an
      instrument for early prediction and identification of low engagement in at-risk
      parents of late preterm infants. The Parent Risk Evaluation and Engagement Model
      and Instrument (PREEMI), its theoretical underpinnings, instrument design, and
      practical application and future research are discussed. 

PMID- 25580953
TI  - Genetic evidence for ecological divergence in kokanee salmon.
AB  - The evolution of locally adapted phenotypes among populations that experience
      divergent selective pressures is a central mechanism for generating and
      maintaining biodiversity. Recently, the advent of high-throughput DNA sequencing
      technology has provided tools for investigating the genetic basis of this process
      in natural populations of nonmodel organisms. Kokanee, the freshwater form of
      sockeye salmon (Oncorhynchus nerka), occurs as two reproductive ecotypes, which
      differ in spawning habitat (tributaries vs. shorelines); however, outside of the
      spawning season the two ecotypes co-occur in many lakes and lack diagnostic
      morphological characteristics. We used restriction site-associated DNA (RAD)
      sequencing to identify 6145 SNPs and genotype kokanee from multiple spawning
      sites in Okanagan Lake (British Columbia, Canada). Outlier tests revealed 18 loci
      putatively under divergent selection between ecotypes, all of which exhibited
      temporally stable allele frequencies within ecotypes. Six outliers were annotated
      to sequences in the NCBI database, two of which matched genes associated with
      early development. There was no evidence for neutral genetic differentiation;
      however, outlier loci demonstrated significant structure with respect to ecotype
      and had high assignment accuracy in mixed composition simulations. The absence of
      neutral structure combined with a small number of highly divergent outlier loci
      is consistent with theoretical predictions for the early stages of ecological
      divergence. These outlier loci were then applied to a realistic fisheries
      scenario in which additional RAD sequencing was used to genotype kokanee
      collected by trawl in Okanagan Lake, providing preliminary evidence that this
      approach may be an effective tool for conservation and management. 

PMID- 25580954
TI  - Vortex flows impart chirality-specific lift forces.
AB  - Recent reports that macroscopic vortex flows can discriminate between chiral
      molecules or their assemblies sparked considerable scientific interest both for
      their implications to separations technologies and for their relevance to the
      origins of biological homochirality. However, these earlier results are
      inconclusive due to questions arising from instrumental artifacts and/or
      insufficient experimental control. After a decade of controversy, the question
      remains unresolved-how do vortex flows interact with different stereoisomers?
      Here, we implement a model experimental system to show that chiral objects in a
      Taylor-Couette cell experience a chirality-specific lift force. This force is
      directed parallel to the shear plane in contrast to previous studies in which
      helices, bacteria and chiral cubes experience chirality-specific forces
      perpendicular to the shear plane. We present a quantitative hydrodynamic model
      that explains how chirality-specific motions arise in non-linear shear flows
      through the interplay between the shear-induced rotation of the particle and its
      orbital translation. The scaling laws derived here suggest that rotating flows
      can be used to achieve chiral separation at the micro- and nanoscales. 

PMID- 25580955
TI  - A case report of differentiating staphylococcal scalded skin syndrome and toxic
      epidermal necrolysis by optical coherence tomography.
AB  - BACKGROUND: Staphylococcal scalded skin syndrome (SSSS) and toxic epidermal
      necrolysis (TEN) both present with acute onset, high morbidity and significant
      mortality. Rapid diagnosis is therefore of importance. The aim of this study was
      to investigate and compare the presentation of these diseases using optical
      coherence tomography (OCT). METHODS: Two male patients with bullous diseases,
      SSSS and TEN, respectively, were photographed digitally, examined using
      dermoscopy, OCT scanned and subsequently biopsied in the said order. RESULTS: The
      bullous skin was visualized by OCT showing two distinct images: the SSSS-patient
      displayed superficial hyporefletive flaccid structures with a split high in the
      thickened (0.51 mm vs. 0.12 mm) epidermis while the TEN-patient demonstrated a
      larger hyporeflective ovoid structure with a split right below the thickened
      epidermis (0.18 mm vs. 0.06 mm). CONCLUSION: These findings suggest that there is
      a potential for the application of OCT scanning in the acute phase of SSSS and
      TEN in order to distinguish them for a faster diagnosis and better management and
      treatment.

PMID- 25580956
TI  - Corrigendum: IL-37 protects against obesity-induced inflammation and insulin
      resistance.

PMID- 25580957
TI  - Subclinical thyroid dysfunction and psychiatric disorders: cross-sectional
      results from the Brazilian Study of Adult Health (ELSA-Brasil).
AB  - OBJECTIVE: To evaluate the association between subclinical thyroid dysfunction
      and psychiatric disorders using baseline data from the Brazilian Longitudinal
      Study of Adult Health (ELSA-Brasil). DESIGN: Cross-sectional study. PATIENTS: The
      study included 12 437 participants from the ELSA-Brasil with normal thyroid
      function (92.8%), 193 (1.4%) with subclinical hyperthyroidism and 784 (5.8%) with
      subclinical hypothyroidism, totalling 13 414 participants (50.6% of women).
      MEASUREMENTS: The mental health diagnoses of participants were assessed by
      trained raters using the Clinical Interview Schedule - Revised (CIS-R) and
      grouped according to the International Classification of Diseases 10 (ICD-10).
      Thyroid dysfunction was assessed using TSH and FT4 as well as routine use of
      thyroid hormones or antithyroid medications. Logistic models were presented using
      psychiatric disorders as the dependent variable and subclinical thyroid disorders
      as the independent variable. All logistic models were corrected for multiple
      comparisons using Bonferroni correction. RESULTS: After multivariate adjustment
      for possible confounders, we found a direct association between subclinical
      hyperthyroidism and panic disorder odds ratio [OR], 2.55; 95% confidence Interval
      (95% CI), 1.09-5.94; and an inverse association between subclinical
      hypothyroidism and generalized anxiety disorder (OR, 0.75; 95% CI, 0.59-0.96).
      However, both lost significance after correction for multiple comparisons.
      CONCLUSION: Subclinical hyperthyroidism was positively associated with panic
      disorder and negatively associated with anxiety disorder, although not
      significant after adjustment for multiple comparisons.

PMID- 25580958
TI  - Dose-responses of zinc-methionine supplements on growth, blood metabolites and
      gastrointestinal development in sheep.
AB  - The effects of zinc-methionine (Zn-Met) supplementation on growth, blood
      metabolites and gastrointestinal development were investigated in two experiments
      with sheep. The objective of Experiment 1 was to determine the effects of Zn-Met
      supplementation on hormones and metabolites involved in growth and energy balance
      regulation, while Experiment 2 aimed to determine the effects of Zn-Met on feed
      intake, body weight, gastrointestinal development and liver glycogen
      concentration in lamb. The animals were assigned to groups with different
      concentrations of dietary Zn-Met (0, 0.4, 0.8 and 1.2 g/day) in both experiments.
      In Experiment 1, feeding different doses of Zn-Met increased plasma insulin-like
      growth factor 1 (IGF-1) concentration, but it linearly decreased plasma growth
      hormone (GH). No differences were observed in blood cortisol, insulin and glucose
      concentrations among the treatments. In Experiment 2, addition of Zn-Met to the
      diets did not lead to changes in the body weights of the lambs. Both average
      daily gain and dry matter intake (DMI) increased linearly with increasing
      concentrations of dietary Zn-Met. Lambs receiving Zn-Met showed higher liver
      glycogen concentrations than the control. While significant increases were
      observed in the villus height and crypt depth in the duodenum and jejunum as a
      result of Zn-Met supplementation, no change was detected in blood glucose
      concentrations (p > 0.05). Our findings suggest that dietary Zn-Met may improve
      growth, energy balance and gastrointestinal development in sheep. 

PMID- 25580959
TI  - Utility of real-time shear wave elastography for assessing liver fibrosis in
      patients with chronic hepatitis C infection without cirrhosis: Comparison of
      liver fibrosis indices.
AB  - AIM: To clarify the diagnostic impact of liver fibrosis except for cirrhosis
      identified using shear wave elastography (SWE) in chronic hepatitis C (CHC)
      patients, and to compare the performance in diagnosing liver fibrosis among SWE
      and liver fibrosis indices. METHODS: A total of 55 CHC patients who underwent
      liver biopsy were analyzed. The diagnostic performance for identifying
      significant liver fibrosis (F2-F3) for SWE, FIB-4 index, aspartate
      aminotransferase-to-platelet ratio index (APRI) and Forns' index was assessed
      using receiver-operator curve (ROC) analysis. RESULTS: The median SWE elasticity
      value, FIB-4 index, APRI and Forns' index in the F0-F1 and F2-F3 groups were 6.3
      kPa and 13.1 kPa; 1.52 and 4.45; 0.41 and 1.43; and 7.69 and 8.85, respectively
      (P < 0.001 for all four methods). Multivariate analysis showed that SWE was
      independently associated with the presence of significant liver fibrosis (odds
      ratio, 2.52; 95% confidence interval, 1.49-4.28; P < 0.001). The area under the
      ROC curve for SWE in diagnosing significant liver fibrosis was 0.94, indicating
      high diagnostic value, compared with 0.86, 0.88 and 0.83, for the FIB-4 index,
      APRI and Forns' index, respectively, which corresponds to moderate diagnostic
      value. The accuracy of SWE, FIB-4 index, APRI and Forns' index for diagnosing
      significant liver fibrosis was 90.9%, 76.4%, 74.5% and 67.2%, respectively.
      CONCLUSION: SWE has excellent ability for diagnosing significant liver fibrosis
      in CHC even when patients with cirrhosis are excluded. The diagnostic performance
      of SWE is superior to that of three liver fibrosis indices.

PMID- 25580960
TI  - Pharmaceutical industry, academia and patient advocacy organizations: what is the
      recipe for synergic (win-win-win) collaborations?
AB  - Biological complexity and the need for highly differentiated medicines means that
      drug discovery and development have become increasingly challenging and
      expensive. Thus, new paradigms for research and drug development need to be
      created that bring together a wide array of expertise. One potential solution is
      collaboration between bio-pharma and academic research centres. Two examples are
      discussed, one with a large pharma company (GlaxoSmithKline) and the other a
      small biotech (Genoa Pharmaceuticals). Patient advocacy organization can also
      have role in assisting in the creation of these partnerships by informing
      patients of ongoing research and clinical trials, and supporting the development
      of networks that can provide major benefit for both basic research and drug
      development. A major 'hurdle' for the creation of these relationships is the
      issue of intellectual property. Examples are provided of how this issue can be
      resolved. 

PMID- 25580962
TI  - [Intensive care: early artificial nutrition: are enteral and parenteral feeding
      equivalent?].

PMID- 25580963
TI  - [Bleeding ulcers: prevention of relapse: continuous PPI use no better than
      intermittent].

PMID- 25580964
TI  - [Intensive care: glutamine administration for critically ill patients is of
      limited use].

PMID- 25580965
TI  - [Infectious diseases - Pulmonology: Haemophilus vaccine against exacerbations in
      COPD/bronchitis?].

PMID- 25580966
TI  - [71-year-old man after partial resection of the right kidney].

PMID- 25580967
TI  - [Tackling obesity with an interdisciplinary approach: a medical, health policy
      and economic challenge].

PMID- 25580968
TI  - [Obesity: causes and consequences].

PMID- 25580969
TI  - [Conservative obesity treatment - when and how?].
AB  - With a prevalence of 24 %, obesity is a frequent disease in the general
      population in Germany. Obesity requires an effective prevention and treatment,
      mainly because it significantly increases the risk of developing type 2 diabetes,
      cardiovascular, orthopaedic, psychologic and other disorders. The indication for
      the treatment of obesity is based on BMI and body fat distribution, but also
      includes considerations based on comorbidities. Main treatment goals include body
      weight reduction and weight maintenance after weight loss. To achieve these
      goals, a conservative treatment strategy is primarily recommended which consists
      of energy-reduced diet with a daily deficit of 500 kcal, increased physical
      activity, behavioral modifications or treatment. Several multimodal conservative
      treatment programs have been evaluated. If individual treatment targets could not
      be achieved, stepwise conservative treatment intensification should be initiated
      with very low calorie diets, pharmacotherapy and / or endoscopic obesity
      therapies. Surgical interventions represent an additional step in the obesity
      treatment algorithm, which have been shown to be more effective than conservative
      approaches with regard to weight and body fat reduction, improvement in obesity
      related comorbidities, long-term weight maintenance and reduced mortality. 

PMID- 25580970
TI  - [Obesity: when to ask the surgeon].

PMID- 25580971
TI  - [How to do: Radiofrequency thermal ablation].

PMID- 25580972
TI  - [Spontaneous rupture of aneurysmatic pulmonary artery in homozygotic alpha-1
      antitrypsin deficiency].
AB  - History and clinical findings | A 57-year-old woman with a history of
      emphysematous COPD GOLD D and homozygotic alpha-1-antitrypsin deficiency
      presented with aggravated dyspnoea, presyncope and left thoracic chest pain. 12
      years previously Stanford type B dissection had been conservatively treated.
      Examinations | Chest radiograph revealed extended infiltrates of the left lower
      lobe. Seen together with elevated inflammatory values and the patient's
      hemodynamic instability it pointed at a pneumonia-driven septic shock. In view of
      a progressive respiratory insufficiency and an acute drop in haemoglobin computed
      tomography was performed. It showed rupture of an aneurysmatic left lower
      pulmonary artery with consecutive intraparenchymal bleeding. Treatment and course
      | Because of persistent bleeding and respiratory failure requiring invasive
      ventilation, thoracotomy was performed. Left lower pulmonary artery was sutured
      and left lower lobe resected. After initial postoperative stabilization
      bronchopleural fistula demanded re-thoracotomy and parenchymal lesions of left
      upper lobe were sutured. In consequence of progressive sepsis and manifest
      multiorgan failure patient died 15 days after initial surgical bleeding control.
      Conclusion | Though homozygotic alpha-1-antitrypsin deficiency is primarily
      associated with lung and liver disease, extrapulmonary and extrahepatic
      manifestation may occur. In view of consistent case reports and plausible
      pathogenetic mechanisms, vascular complications comprising arterial aneurysms and
      dissection due to compromised vascular integrity in alpha-1-antitrypsin deficient
      individuals is conceivable, but lacks scientific proof. 

PMID- 25580973
TI  - [Treatment options for serious infections caused by vancomycin-resistant
      enterococci].
AB  - Complicated infections caused by vancomycin-resistant enterococci (VRE) represent
      a therapeutic challenge, since adequate treatment options are limited and
      antibiotic resistance to the available agents has already been described. The
      most frequently used antibiotic in VRE treatment is linezolid. Tigecycline is an
      alternative to linezolid, however, clinical data for severe infections such as
      sepsis or endocarditis are scarce. Daptomycin on the one hand is an option but
      has not yet been approved for the treatment of enterococcal infections in Germany
      on the other hand. The present review critically evaluates the clinical
      significance of the antibiotics in question for VRE therapy based on existing
      data. 

PMID- 25580974
TI  - [Value of ultrasound in diagnostic and follow-up of chronic inflammatory bowel
      diseases].
AB  - Transabdominal ultrasound as an easy to use, accurate, cost-effective and
      pleasant method has emerged as one of the most important imaging techniques in
      daily routine. Ultrasound is efficient for the diagnosis and differentiation of
      chronic inflammatory bowel diseases (IBD). For monitoring disease activity and
      severity as well as identifying complications (stenosis, abscess and fistula)
      high-resolution ultrasonography with Doppler techniques and contrast-enhanced
      ultrasonography (CEUS) is well suited. Perineal ultrasound and extravascular CEUS
      can give important information for clinical management of patients with IBD. The
      aim of this article is to give an updated overview about the clinical
      applications of ultrasound in the diagnosis and followup of patients with IBD. 

PMID- 25580975
TI  - [Assessment of occupational cancer: important facts to consider].
AB  - Background | Persons suffering from malignant tumors who had been exposed to
      carcinogens at their workplace must be compensated if occupational exposure
      probably caused the disease. However, the assessment of the causes of cancers is
      particularly difficult.Method | For the evaluation the authors analyzed
      selectively researched literature and considered publications of the German
      Social Accident Insurance and legal regulations.Result | Often the quantification
      of the occupational exposure is not possible. Cumulative exposures neglect
      important factors, e.g. high peak concentrations. Even in the general population
      exposure to noxious agents occurs. This raises the question what amount of
      occupational exposure must be considered as sufficient for compensation and how
      non-occupational factors, such as genetic susceptibility, should influence the
      expert's opinion. Syncancerogenetic effects are currently not sufficiently
      considered in the legal ordinance on occupational diseases.Conclusion | At best,
      only a very rough estimate of the probability of causation can be stated. If
      there is insufficient scientific evidence then there is a need of "makeshift"
      recommendations within the social consensus, which occupational exposure is
      considered to be relevant for occupational disease. If there are no reliable data
      on occupational exposure due to failure of the employer, this should not be
      stacked against the insured. 

PMID- 25580976
TI  - [Mild therapeutic hypothermia after cardiopulmonary resuscitation - yes].

PMID- 25580977
TI  - [Mild therapeutic hypothermia after cardiopulmonary resuscitation - no].

PMID- 25580978
TI  - [How to delegate correctly - transferring physicians' tasks to assistance
      personnel].

PMID- 25580979
TI  - [High versus moderate intense running exercise - effects on cardiometabolic risk
      factors in untrained males].
AB  - Introduction | The philosophy on how to improve cardiometabolic risk factors most
      efficiently by endurance exercise is still controversial. To determine the effect
      of high-intensity (interval) training (HI[I]T) vs. moderate-intensity continuous
      exercise (MICE) training on cardiometabolic risk factors we conducted a 16-week
      crossover randomized controlled trial. Methods | 81 healthy untrained middle aged
      men were randomly assigned to a HI(I)T-group and a control-group that started the
      MICE running program after their control status. HI(I)T consisted of running
      exercise around or above the individual anaerobic threshold (~ 80- 100 % HRmax);
      MICE focused on continuous running exercise at ~ 65-77.5 % HRmax. Both protocols
      were comparable with respect to energy consumption. Study endpoints were
      cardiorespiratory fitness (VO2max), left ventricular mass index (LVMI), metabolic
      syndrome Z-score (MetS-Z-score), intima-media-thickness (IMT) and body
      composition. Results | VO2max-changes in this overweighed male cohort
      significantly (p=0.002) differ between HIIT (14.7 +/- 9.3 %, p=0.001) and MICE
      (7.9 +/- 7.4 %,p=0.001). LVMI, as determined via magnetic resonance imaging,
      significantly increased in both exercise groups (HIIT: 8.5 +/- 5.4 %, p=0.001 vs.
      MICE: 5.3 +/- 4.0 %, p=0.001), however the change was significantly more
      pronounced (p=0.005) in the HIIT-group. MetS-Z-score (HIIT: -2.06 +/- 1.31,
      p=0.001 vs. MICE: -1.60 +/- 1.77, p=0.001) and IMT (4.6 +/- 5.9 % p=0.011 vs. 4.4
      +/- 8.1 %, p=0.019) did not show significant group-differences. Reductions of fat
      mass (-4.9 +/- 9.0 %, p=0.010 vs. -9.5 +/- 9.4, p=0.001) were significantly
      higher among the MICE-participants (p=0.034), however, the same was true
      (p=0.008) for lean body mass (0.5 +/- 2.3 %, p=0.381 vs. -1.3 +/- 2.0 %,
      p=0.003). Conclusion | In summary high-intensity interval training tends to
      impact cardiometabolic health more favorable compared with a moderate-intensity
      continuous endurance exercise protocol. 

PMID- 25580980
TI  - Uterine artery pseudoaneurysm after non-traumatic vaginal delivery as a cause of
      postpartum hemorrhage: determination of its mechanism is urgently needed.

PMID- 25580981
TI  - Phytohormones as integrators of environmental signals in the regulation of
      mycorrhizal symbioses.
AB  - For survival, plants have to efficiently adjust their phenotype to environmental
      challenges, finely coordinating their responses to balance growth and defence.
      Such phenotypic plasticity can be modulated by their associated microbiota. The
      widespread mycorrhizal symbioses modify plant responses to external stimuli,
      generally improving the resilience of the symbiotic system to environmental
      stresses. Phytohormones, central regulators of plant development and immunity,
      are instrumental in orchestrating plant responses to the fluctuating environment,
      but also in the regulation of mycorrhizal symbioses. Exciting advances in the
      molecular regulation of phytohormone signalling are providing mechanistic
      insights into how plants coordinate their responses to environmental cues and
      mycorrhizal functioning. Here, we summarize how these mechanisms permit the fine
      tuning of the symbiosis according to the ever-changing environment.

PMID- 25580982
TI  - Low testosterone has a similar prevalence among men with sexual dysfunction due
      to either Peyronie's disease or erectile dysfunction and does not correlate with
      Peyronie's disease severity.
AB  - INTRODUCTION: Low testosterone (T) has been suggested as a risk factor for
      Peyronie's disease (PD) that may correlate with disease severity. Low T is common
      in men with sexual dysfunction but its role in the pathogenesis of PD remains
      unclear. AIM: The aim of this study was to compare the prevalence of low T (<300
      ng/dL) in patients presenting with PD or erectile dysfunction (ED), as well as
      disease severity between men with PD and either low T or normal T (>=300 ng/dL).
      METHODS: Retrospective review of 300 men with either PD or ED was conducted. Men
      were excluded for combined PD and ED, psychogenic ED, or prior T use. For men
      with PD, plaque size, degree of curvature, and surgical correction rate were
      compared. MAIN OUTCOME MEASURES: The main outcome measures were (i) mean T levels
      in men with PD or ED and (ii) plaque size, degree of curvature, and surgical
      correction rates among men with PD and either low T or normal T. RESULTS: Eighty
      seven men with PD and 98 men with ED were identified. Men with PD had mean total
      T and free T of 328 ng/dL and 11.5 ng/dL, while men with ED had mean levels of
      332 ng/dL and 12.1 ng/dL, respectively (P > 0.05). Of PD men, 52.9% had low T,
      compared with 45.9% of men with ED (P = 0.35). T levels did not correlate with
      plaque size or degree of curvature in the PD group (P > 0.05). CONCLUSIONS: Men
      with sexual dysfunction characterized by either PD or ED had similarly low T
      levels, and low T did not correlate with PD severity or surgical correction rate.
      The comparable prevalence of low T in men with PD or ED suggests the high rate of
      low T in PD men may be related to a common process among men with abnormal
      erectile physiology and not specifically causative in plaque formation.

PMID- 25580983
TI  - An improved method for evaluating ideal standards in self-perception and mate
      preferences.
AB  - The aim of the study was to improve the methodology for measuring ideals of self
      perception and mate preferences. The Ideal Standards Model (ISM; Fletcher,
      Simpson, Thomas & Giles, 1999) was used as a basis for development of the scale.
      It was further modified by adding a number of items from previous studies. Data
      were collected from 223 participants, aged 19 to 27 years. The results suggested
      that a modified five-factor version of the ISM is an appropriate method for
      evaluation of ideal characteristics. The five factors are warmth/
      trustworthiness, status/ resources, intelligence, social skills and physical
      attractiveness.

PMID- 25580984
TI  - Emergence delirium, pain or both? A challenge for clinicians.
AB  - BACKGROUND: Children commonly display early postoperative negative behavior (e
      PONB) after general anesthesia, which includes emergence delirium (ED),
      discomfort, temperament, and pain. However, it is often difficult for the
      caregiver to discriminate between various aspects of e-PONB. OBJECTIVE: This
      prospective observational study evaluates the possibility to distinguish between
      ED and pain in young children using validated pediatric observational scales in
      the early postoperative phase. METHODS: Following institutional approval and
      written consent, children undergoing elective adenoidectomy and/or tonsillectomy
      were enrolled. Following standardized anesthesia, two trained observers
      simultaneously evaluated children's behavior with the Paediatric Anaesthesia
      Emergence Delirium Scale (PAED) and with the Face, Legs, Activity, Cry,
      Consolability scale (FLACC) at extubation, and at 5, 10, and 15 min. RESULTS: Of
      150 children that completed the study, 32 (21%) had ED, 7 (5%) had pain, and 98
      (65%) had simultaneously both ED and pain. The association of 'No eye contact',
      'No purposeful action' and 'No awareness of surroundings' (ED1) had a sensitivity
      of 0.96 and a specificity of 0.80 (PPV 0.97, NPV 0.78) to identify ED.
      'Inconsolability' and 'Restlessness' (ED2) had a sensitivity of 0.69 and a
      specificity of 0.88 (PPV 0.83 and NPV 0.78) to identify pain. CONCLUSION: It is
      difficult to differentiate between ED and pain using FLACC and PAED scores. 'No
      eye contact', 'No purposeful action', and 'No awareness of surroundings'
      significantly correlated with ED. 'Inconsolability' and 'Restlessness' are not
      reliable enough to identify pain or ED in the first 15 min after awakening.

PMID- 25580985
TI  - Infliximab reverses inflammatory muscle wasting (sarcopenia) in Crohn's disease.
AB  - BACKGROUND: Muscle wasting or sarcopenia arising from chronic inflammation is
      found in 60% of patients with Crohn's disease. Transcriptional protein NF-kappaB
      reduces muscle formation through MyoD transcription and increases muscle
      breakdown by proteolysis. AIM: As TNF is a potent activator of NF-kappaB, and
      anti-TNF agent infliximab (IFX) prevents NF-kappaB activation, to determine
      whether or not Crohn's patients treated with IFX gain muscle volume and strength.
      METHODS: We performed a prospective, repeated-measures cohort study in adult
      Crohn's disease patients with an acute disease flare. Patients were instructed
      not to vary diet or activity. Concomitant medications were kept stable. At week 1
      (pre-treatment), week 16 (post-IFX induction) and week 25 (post-first IFX
      maintenance dose), we assessed (i) MRI volume of quadriceps femoris at anatomical
      mid-thigh; (ii) maximal concentric quadriceps contractions strength at three
      specific speeds of contraction; (iii) physical activity by validated instrument
      (IPAQ); (iv) Three-day food record of intake and composition (food-weighing
      method); (v) Serum levels of IL6. RESULTS: Nineteen patients (58% female; mean
      age 33.2 +/- 10.7 years) were recruited. IFX increased muscle volume in both legs
      from baseline (right, 1505 cm(3) ) to week 25 (right, 1569 cm(3) ; P = 0.010).
      IFX also increased muscle strength in both legs from baseline (right 30 degrees
      /s, 184.8 Nm) to week 25 (right 30 degrees /s, 213.6 Nm; P = 0.002). Muscle
      volume gain correlated with male gender (P = 0.003). Significant gains in muscle
      volume and strength were unrelated to prednisolone use. Serum IL6 levels
      decreased by week 25 (P = 0.037). CONCLUSION: The anti-TNF agent infliximab
      reverses inflammatory sarcopenia in patients with Crohn's disease.

PMID- 25580986
TI  - The association of ankle-brachial index with silent cerebral small vessel
      disease: results of the Atahualpa Project.
AB  - BACKGROUND: An abnormal ankle-brachial index has been associated with overt
      stroke and coronary heart disease, but little is known about its relationship
      with silent cerebral small vessel disease. AIM: To assess the value of ankle
      brachial index as a predictor of silent small vessel disease in an Ecuadorian
      geriatric population. METHODS: Stroke-free Atahualpa residents aged >=60 years
      were identified during a door-to-door survey. Ankle-brachial index determinations
      and brain magnetic resonance imaging were performed in consented persons. Ankle
      brachial index <=0.9 and >=1.4 were proxies of peripheral artery disease and
      noncompressible arteries, respectively. Using logistic regression models adjusted
      for age, gender, and cardiovascular health status, we evaluated the association
      between abnormal ankle-brachial index with silent lacunar infarcts, white matter
      hyperintensities, and cerebral microbleeds. RESULTS: Mean age of the 224
      participants was 70 +/- 8 years, 60% were women, and 80% had poor cardiovascular
      health status. Ankle-brachial index was <=0.90 in 37 persons and >=1.4 in 17.
      Magnetic resonance imaging showed lacunar infarcts in 27 cases, moderate-to
      severe white matter hyperintensities in 47, and cerebral microbleeds in 26.
      Adjusted models showed association of lacunar infarcts with ankle-brachial index
      <= 0.90 (OR: 3.72, 95% CI: 1.35-10.27, P = 0.01) and with ankle-brachial index >=
      1.4 (OR: 3.85, 95% CI: 1.06-14.03, P = 0.04). White matter hyperintensities were
      associated with ankle-brachial index <= 0.90 (P = 0.03) and ankle-brachial index
      >= 1.4 (P = 0.02) in univariate analyses. There was no association between ankle
      brachial index groups and cerebral microbleeds. CONCLUSIONS: In this population
      based study conducted in rural Ecuador, apparently healthy individuals aged >=60
      years with ankle-brachial index values <=0.90 and >=1.4 are almost four times
      more likely to have a silent lacunar infarct. Ankle-brachial index screening
      might allow recognition of asymptomatic people who need further investigation and
      preventive therapy.

PMID- 25580987
TI  - Melatonin potentiates cisplatin-induced apoptosis and cell cycle arrest in human
      lung adenocarcinoma cells.
AB  - OBJECTIVES: Melatonin produces anti-cancer effects via several mechanisms,
      including by induction of apoptosis. In this way, it has been shown to be of use,
      in combination with chemotherapeutic drugs, for cancer treatment. The study
      described here has evaluated effects of melatonin on cytotoxicity, apoptosis and
      cell cycle arrest induced with the chemotherapeutic agent cisplatin, in human
      lung adenocarcinoma cisplatin-sensitive cell line (SK-LU-1), which previously had
      only limit data. MATERIALS AND METHODS: Cells of the SK-LU-1 line were treated
      with melatonin alone at 1-5 mM concentration or cisplatin alone 10-200 MUM, for
      48 h in culture. Cytotoxicity was measured by MTT reduction assay. Apoptosis
      induction was detected by annexin V/PI staining using flow cytometric analysis
      and DAPI nuclear staining. Change in mitochondrial membrane potential (DeltaPsim)
      was quantified using DiOC6(3) reagent and activities of caspases-3/7 were also
      investigated. DNA fractions were measured using propidium iodide (PI) staining.
      RESULTS: Melatonin or cisplatin alone had 50% (IC50 ) cytotoxicity at 5 mM or 34
      MUM concentrations respectively. Combination of 1 or 2 mM melatonin and cisplatin
      significantly augmented cytotoxicity of cisplatin by reducing its IC50 to 11 and
      4 MUM, respectively. Consistently, combined treatment increased population of
      apoptotic cells by elevating mitochondrial membrane depolarization, activating
      caspases-3/7 and inducing cell cycle arrest in the S phase, compared to treatment
      with cisplatin alone. CONCLUSION: These data demonstrate that melatonin enhanced
      cisplatin-induced cytotoxicity and apoptosis in SK-LU-1 lung cancer cells. SK-LU
      1 cell population growth inhibition was mediated by cell cycle arrest in the S
      phase. These findings suggest that melatonin has the potential to be used for
      NSCLC treatment in combination with a chemotherapeutic agent such as cisplatin.

PMID- 25580988
TI  - Multimodal treatment of unresectable hepatocellular carcinoma to achieve complete
      response results in improved survival.
AB  - INTRODUCTION: With technological advances, questions arise regarding how to best
      fit newer treatment modalities, such as transarterial therapies, into the
      treatment algorithm for patients with hepatocellular carcinoma (HCC). METHODS:
      Between 2005 and 2011, 128 patients initially treated with transarterial
      radioembolization or chemoembolization using drug-eluting beads were identified.
      The response was graded retrospectively. Toxicity was measured 1, 3, and 6 months
      after the first and last treatments. RESULTS: Sixty-five patients (53%) were
      advanced stage. Twenty patients (16%) had an initial complete response, but with
      additional treatments, this was increased to 46 (36%). Patients with a complete
      response as their best response to treatment had a median survival [95%
      confidence interval (CI)] of 5.77 (2.58, upper limit not yet reached) years,
      significantly longer than those whose best response was a partial response, 1.22
      (0.84, 2.06) years and those with stable disease as their best response, 0.34
      (0.29, 0.67) years. Repeated treatments did not increase toxicity. DISCUSSION:
      This retrospective review of patients treated for intermediate and advanced stage
      HCC revealed a significant survival advantage in patients who achieved a complete
      response. These data support use of a multi-modality approach to intermediate and
      advanced stage HCC, combining liver-directed treatments as necessary to achieve a
      complete response.

PMID- 25580989
TI  - Postoperative analgesia with continuous wound infusion of local anaesthesia vs
      saline: a double-blind randomized, controlled trial in colorectal surgery.
AB  - AIM: The aim of this prospective double-blind randomized clinical trial was to
      determine whether preperitoneal continuous wound infusion (CWI) of the local
      anaesthetic ropivacaine after either laparotomy or video-assisted laparoscopy for
      colorectal surgery would reduce patient consumption of morphine. METHOD: Patients
      scheduled for colorectal surgery randomly received a 48-h preperitoneal CWI of
      either 0.38% ropivacaine or 0.9% saline at rates of 5 ml/h after laparotomy or 2
      ml/h after laparoscopy. The primary end-point was total morphine consumption in
      surgery and afterwards through a patient-controlled analgesia device. Results in
      the laparotomy and laparoscopy subgroups were also compared. RESULTS: Sixty-seven
      patients were included, 33 in the ropivacaine CWI group and 34 in the saline
      group. Median [interquartile range (IQR)] morphine consumption was lower in the
      ropivacaine group [23.5 mg (11.25-42.75)] than in the saline group [52 mg (24.5
      64)] (P = 0.010). Morphine consumption was also lower in the laparotomy subgroup
      receiving ropivacaine [21.5 (15.6-34.7)] than in the saline group [52.5 (22.5-65)
      ml] (P = 0.041). Consumption was statistically similar in laparoscopy patients on
      ropivacaine or saline. No side effects were observed. Sixteen patients had a
      surgical wound infection (23.9%); 11 (16.4%) presented wound infection and five
      (7.5%) organ space infection. Forty-six catheter cultures were obtained; 10
      (21.7%) were positive, assessed to be due to contamination. CONCLUSION:
      Preperitoneal CWI of ropivacaine is a good, safe addition to a multimodal
      analgesia regimen for colorectal surgery. CWI can reduce morphine consumption
      without increasing adverse effects.

PMID- 25580990
TI  - Age-dependent changes in damage processes of hair cuticle.
AB  - BACKGROUND: Human hair cuticle is always exposed to various stresses and then
      gradually lost in daily life. There are two typical patterns of cuticle damage:
      type L, where the cell membrane complex, the structure located between cuticle
      cells, is split and the cuticle lifts up, and type E, where the fragile
      substructure of the cuticle cell (endocuticle) is damaged so that its rugged
      residue is exposed. We previously reported that type L damage preferentially
      occurs in the case of Japanese females in their 20s to 40s. AIMS: This study aims
      to elucidate the age-dependent change of cuticle and its effect on hair
      properties. METHODS: Hair fibers collected from Japanese females (ranging from 10
      to 70 years old) were evaluated in the aspects of inclination for each type of
      damage, resistance of cuticle against grooming stresses and content of fatty acid
      18-MEA on hair surface. RESULTS: It was revealed that the dominant damage pattern
      shifts from type L to E with aging. Furthermore, the cuticle becomes gradually
      less resistant to daily grooming stress. The dominance of type E damage
      accelerates cuticle loss. Reduction of 18-MEA on weathered hair is accelerated
      with aging on elder hair. CONCLUSIONS: It has been reported that various age
      dependent changes of whole hair shaft, such as diameter, density, elasticity,
      etc., occur in the age range of 40s and 50s. In this study, it was revealed that
      cuticle becomes more fragile and the hair surface properties deteriorate in the
      same age range.

PMID- 25580991
TI  - Annealing free, clean graphene transfer using alternative polymer scaffolds.
AB  - We examine the transfer of graphene grown by chemical vapor deposition (CVD) with
      polymer scaffolds of poly(methyl methacrylate) (PMMA), poly(lactic acid) (PLA),
      poly(phthalaldehyde) (PPA), and poly(bisphenol A carbonate) (PC). We find that
      optimally reactive PC scaffolds provide the cleanest graphene transfers without
      any annealing, after extensive comparison with optical microscopy, x-ray
      photoelectron spectroscopy, atomic force microscopy, and scanning tunneling
      microscopy. Comparatively, films transferred with PLA, PPA, PMMA/PC, and PMMA
      have a two-fold higher roughness and a five-fold higher chemical doping. Using PC
      scaffolds, we demonstrate the clean transfer of CVD multilayer graphene,
      fluorinated graphene, and hexagonal boron nitride. Our annealing free, PC
      transfers enable the use of atomically-clean nanomaterials in biomolecule
      encapsulation and flexible electronic applications. 

PMID- 25580992
TI  - Safety of lumbar spine radiofrequency procedures in the presence of posterior
      pedicle screws: technical report of a cadaver study.
AB  - OBJECTIVE: To determine whether the thermal energy associated with lumbar spine
      radiofrequency neurotomy (RFN) performed near titanium and stainless steel
      pedicle screws is conducted to the pedicle screws or adjacent tissues, or both,
      thus introducing potential for thermal damage to those tissues. DESIGN: Cadaver
      study. SETTING: Cadaver laboratory equipped with fluoroscopy, surgical spine
      implements, and radiofrequency generator. SUBJECTS: No live human subject; a
      fresh frozen (and thawed) cadaver torso was used for the study. METHODS: Titanium
      and stainless steel pedicle screws were placed in the lumbar spine of a fresh
      frozen cadaver torso with real-time fluoroscopic guidance. Conventional RFN
      cannula placement was performed at the level of pedicle screws and a control
      (nonsurgically altered) lumbar level. Neurotomy was performed with conventional
      radiofrequency lesioning parameters. Temperatures were recorded at multiple sites
      through thermistor probes. RESULTS: Direct contact of the radiofrequency cannula
      with the pedicle screws during conventional RFN produced a substantial increase
      in temperature in the surrounding soft tissues. A small increase in temperature
      occurred at the same sites at the control level. CONCLUSIONS: Titanium and
      stainless steel pedicle screws are capable of sustaining large increases in
      temperature when the radiofrequency probe comes in contact with the screw. These
      results are suggestive that pedicle screws could serve as a possible source of
      tissue heating and thermal injury during RFN.

PMID- 25580993
TI  - Methane oxidation coupled to nitrate reduction under hypoxia by the
      Gammaproteobacterium Methylomonas denitrificans, sp. nov. type strain FJG1.
AB  - Obligate methanotrophs belonging to the Phyla Proteobacteria and Verrucomicrobia
      require oxygen for respiration and methane oxidation; nevertheless, aerobic
      methanotrophs are abundant and active in low oxygen environments. While genomes
      of some aerobic methanotrophs encode putative nitrogen oxide reductases, it is
      not understood whether these metabolic modules are used for NOx detoxification,
      denitrification or other purposes. Here we demonstrate using microsensor
      measurements that a gammaproteobacterial methanotroph Methylomonas denitrificans
      sp. nov. strain FJG1(T) couples methane oxidation to nitrate reduction under
      oxygen limitation, releasing nitrous oxide as a terminal product. Illumina RNA
      Seq data revealed differential expression of genes encoding a denitrification
      pathway previously unknown to methanotrophs as well as the pxmABC operon in M.
      denitrificans sp. nov. strain FJG1(T) in response to hypoxia. Physiological and
      transcriptome data indicate that genetic inventory encoding the denitrification
      pathway is upregulated only upon availability of nitrate under oxygen limitation.
      In addition, quantitation of ATP levels demonstrates that the denitrification
      pathway employs inventory such as nitrate reductase NarGH serving M.
      denitrificans sp. nov. strain FJG1(T) to conserve energy during oxygen
      limitation. This study unravelled an unexpected metabolic flexibility of aerobic
      methanotrophs, thereby assigning these bacteria a new role at the metabolic
      intersection of the carbon and nitrogen cycles.

PMID- 25580994
TI  - Dural lymphoma mimicking subdural haematoma on computerized tomography.

PMID- 25580995
TI  - Culture medium-associated physicochemical insights on the cytotoxicity of carbon
      nanomaterials.
AB  - Carbon nanomaterials are the most studied materials in nanotechnology. There have
      been numerous studies on cytotoxicity assessments of carbon nanomaterials, which,
      however, often lead to controversy. It is generally considered that chemical and
      physical properties of carbon nanomaterials should have specific biological
      outcomes. More recent studies have identified the significance of environmental
      factors surrounding nanomaterial-treated cells. In this perspective, we mainly
      review culture medium-associated physicochemical insights on the cytotoxicity of
      carbon nanomaterials, which are largely based on studies in our laboratory. These
      studies established the close relationship and interplay among the
      physicochemical properties of the nanomaterials, culture medium, and their
      toxicological responses. 

PMID- 25580996
TI  - Correlation between waist:height ratio and serum nitric oxide level in children
      with atopic dermatitis.
AB  - Atopic dermatitis (AD) is the most common chronic inflammatory disease of early
      childhood. This study shows that nitric oxide levels positively correlate with
      the clinical severity of AD, waist:height ratio, and weight. 

PMID- 25580998
TI  - Nanoparticle enlarged interfacial effect on phase transition of 1
      octadecanol/silica composites.
AB  - Motivated by the interest in an interfacial effect on crystallization behaviors
      and material properties of polymer nanocomposites, phase behaviors of a novel
      model system for polymer nanocomposite, 1-octadecanol/silica nanosphere
      composites (C18OH/SiO2), were studied by means of thermal analysis and wide-angle
      X-ray diffraction. Although a huge specific surface area of silica nanoparticles
      enlarges the surface-volume ratio of C18OH molecules, surface freezing phenomenon
      is not observed by DSC in the C18OH/SiO2 composites. While pure C18OH exhibits
      rotator RIV phase with molecules tilted with respect to the layer normal, the
      silica network favors and enhances untitled RII phase by disturbing the layering
      arrangement. Moreover, the confined C18OH shows a polycrystalline mixture of
      orthorhombic beta form and monoclinic gamma form. It is demonstrated that the
      interfacial interaction between the C18OH molecules and the silica surface
      contributes to the peculiar phase transition behaviors of C18OH/SiO2 composites.
      The investigation of the model system of long-chain alcohol/nano-SiO2 composites
      may help us to understand the complicated interfacial effect on phase behaviors
      and material properties of polymer nanocomposite systems. 

PMID- 25580997
TI  - Plumbagin suppresses tumor cell growth in oral squamous cell carcinoma cell
      lines.
AB  - OBJECTIVES: Plumbagin (PL), a naturally occurring quinoid, exerts antitumoral
      effects in diverse types of cancer cells. However, the effect of PL on tumor cell
      proliferation in oral squamous cell carcinoma (OSCC) remains poorly understood.
      In this study, we assessed the efficacy of PL, in human OSCC cells. METHODS: The
      effect of PL on the cell growth and apoptosis of OSCC cell lines was evaluated
      using MTT and Annexin V assays, respectively. The effect of PL on mitochondrial
      membrane potential loss and reactive oxygen species (ROS) generation was
      evaluated using flow cytometry analysis. RESULTS: MTT assay showed that PL dose
      dependently suppressed OSCC cell growth, with IC50 values ranging from 3.87 to
      14.6 MUM. Flow cytometry analysis revealed that PL treatment resulted in a
      significant decrease in mitochondrial membrane potential and an increase in the
      number of apoptotic cells. Notably, ROS generation was significantly elevated
      after PL treatment. Furthermore, a ROS scavenger, N-acetylcysteine (NAC), clearly
      suppressed the decrease in mitochondrial membrane potential, increase of caspase
      3/7 activity, and apoptosis after PL treatment. CONCLUSION: This study provides
      the considerable evidence of the tumor-suppressive effect of PL, thereby
      highlighting its therapeutic potential for OSCC treatment.

PMID- 25580999
TI  - Acinetobacter baumannii infection in solid organ transplant recipients.
AB  - INTRODUCTION: Acinetobacter baumannii can cause serious infection in susceptible
      patients, but little has been published regarding risk factors for infection and
      outcomes in solid organ transplant (SOT) recipients. METHODS: We identified A.
      baumannii infection among adult SOT recipients that occurred between January 2001
      and March 31, 2008 at a Chicago transplant center and evaluated characteristics
      of these infections and outcomes. RESULTS: Thirty-three individuals developed A.
      baumannii infection during the study period. Seventy-nine percent had healthcare
      associated infection with respiratory tract as the most common site of infection
      (64%). Eighty-two percent of patients had received antibiotics within two wk
      prior to A. baumannii infection and multidrug resistance (MDR) or extensive
      resistance (XDR) occurred in 85%. The median time to onset of infection was five
      months after transplant. The 30-d mortality was 24% and was associated with XDR.
      Administration of an appropriate antibiotic within three d was associated with
      lower 30-d mortality (OR 0.16, p = 0.047). All isolates tested against colistin
      were susceptible. CONCLUSION: SOT recipients with A. baumannii infection had high
      mortality associated with delay in appropriate antibiotic therapy and XDR
      organisms. The use of colistin-containing treatment regimens should be considered
      in these patients when A. baumannii infection is suspected or identified in
      patients who have received prior antibiotics.

PMID- 25581001
TI  - State learning disability eligibility criteria: A comprehensive review.
AB  - For many decades, discussions regarding the definition and identification of
      learning disabilities have been contentious; one result is the varied practices
      across states and school districts. This study reviewed learning disability (LD)
      regulations and guidelines from the 50 United States and the District of Columbia
      that were employed during 2013. Two authors independently coded components of all
      LD regulations and guidelines. Results showed considerable variability in the
      state policies and practices governing LD identification. Only 67% of states
      allow for use of the ability-achievement discrepancy approach, and 20% of states
      explicitly prohibit its use. Approximately 16% of states require the sole use of
      response to intervention (RtI) models in LD identification, and there is
      considerable variability in the guidance states provide regarding how to
      implement RtI models to identify LD. Finally, about half of states do not allow
      use of "pattern of strengths and weaknesses" (PSW) models, and most states
      allowing these models provide little information regarding ideal identification
      practices. These results can inform school psychology practice, training, and
      related research.

PMID- 25581002
TI  - Enantioselective approach to polycyclic polyprenylated acylphloroglucinols via
      catalytic asymmetric intramolecular cyclopropanation.
AB  - The formal enantioselective total synthesis of nemorosone, garsubellin A,
      clusianone, and hyperforin is described. The catalytic asymmetric intramolecular
      cyclopropanation (CAIMCP) of an alpha-diazo ketone, a common synthetic
      intermediate for the above four polycyclic polyprenylated acylphloroglucinols
      previously reported by us, exhibited low enantioselectivity. However, CAIMCP of
      the corresponding alpha-diazo beta-keto sulfone afforded the desired product in
      79% yield with 84% ee. Investigation of the CAIMCP of the alpha-diazo beta-keto
      sulfone demonstrated the formation of a rearrangement product in the presence of
      molecular sieves 4 A, whereas, in the presence of H2O, the byproduct derived from
      ring-opening of the desired cyclopropane was observed. X-ray crystallographic
      analysis suggested that the above two products are derived from the same chiral
      intermediate. The product derived from ring-opening of the cyclopropane was
      successfully transformed to the respective synthetic intermediates for the total
      syntheses of nemorosone, garsubellin A, clusianone, and hyperforin, which had
      previously been reported by us. 

PMID- 25581000
TI  - Heritable capture of heterochromatin dynamics in Saccharomyces cerevisiae.
AB  - Heterochromatin exerts a heritable form of eukaryotic gene repression and
      contributes to chromosome segregation fidelity and genome stability. However, to
      date there has been no quantitative evaluation of the stability of
      heterochromatic gene repression. We designed a genetic strategy to capture
      transient losses of gene silencing in Saccharomyces as permanent, heritable
      changes in genotype and phenotype. This approach revealed rare transcription
      within heterochromatin that occurred in approximately 1/1000 cell divisions. In
      concordance with multiple lines of evidence suggesting these events were rare and
      transient, single-molecule RNA FISH showed that transcription was limited. The
      ability to monitor fluctuations in heterochromatic repression uncovered
      previously unappreciated roles for Sir1, a silencing establishment factor, in the
      maintenance and/or inheritance of silencing. In addition, we identified the
      sirtuin Hst3 and its histone target as contributors to the stability of the
      silenced state. These approaches revealed dynamics of a heterochromatin function
      that have been heretofore inaccessible. 

PMID- 25581003
TI  - The future of nursing: monitoring the progress of recommended change in
      hospitals, nurse-led clinics, and home health and hospice agencies.
AB  - OBJECTIVE: The objective of this study was to assess the implementation of
      recommendations of the Institute of Medicine (IOM) report, The Future of Nursing:
      Leading Change, Advancing Health. BACKGROUND: In 2010, the IOM made a series of
      recommendations aimed at transforming the role of nurses in healthcare delivery.
      METHODS: We conducted a multiyear survey, in 2011 and 2013, with nurse leaders
      who were members of the American Organization of Nurse Executives, the National
      Nursing Centers Consortium, or the Visiting Nurses Association of America.
      RESULTS: When comparing 2013 to 2011, we find progress in instituting the IOM's
      recommendations in 3 areas: (1) raising the proportion of employed RNs with at
      least a bachelor's degree; (2) expanding the proportion of healthcare
      institutions with nurse residency programs; and (3) offering opportunities for
      continuing nurse education CONCLUSIONS: Our findings suggest that healthcare
      organizations are transforming to support the recommendations of the IOM.

PMID- 25581004
TI  - The promises of qualitative inquiry.
AB  - We address the significance and implications of the formal entry of qualitative
      inquiry into the American Psychological Association. In our view, the discipline
      is enriched in new and important ways. Most prominently, the qualitative movement
      brings with it a pluralist orientation to knowledge and to practices of inquiry.
      Adding to the traditional view of knowledge as empirically supported theory are
      research practices congenial with varying accounts of knowledge, including, for
      example, knowledge as hermeneutic understanding, social construction, and
      practice-based experience. Added to the goal of prediction are investments in
      increasing cultural understanding, challenging cultural conventions, and directly
      fostering social change. The qualitative movement also enriches the discipline as
      a whole through the special ways in which it inspires new ranges of theory,
      fosters minority inclusion, and invites interdisciplinary collaboration. Finally,
      the movement holds promise in terms of the discipline's contribution to society
      at large. Here we focus on the advantages of knowing with others in addition to
      about them, and on ways in which qualitative work enhances communication with the
      society and the world. Realizing these potentials will depend on developments in
      responsible research and reporting, academic and journal policies, along with the
      discipline's capacities for appreciating a more comprehensive orientation to
      inquiry.

PMID- 25581005
TI  - Evaluating gender similarities and differences using metasynthesis.
AB  - Despite the common lay assumption that males and females are profoundly
      different, Hyde (2005) used data from 46 meta-analyses to demonstrate that males
      and females are highly similar. Nonetheless, the gender similarities hypothesis
      has remained controversial. Since Hyde's provocative report, there has been an
      explosion of meta-analytic interest in psychological gender differences. We
      utilized this enormous collection of 106 meta-analyses and 386 individual meta
      analytic effects to reevaluate the gender similarities hypothesis. Furthermore,
      we employed a novel data-analytic approach called metasynthesis (Zell & Krizan,
      2014) to estimate the average difference between males and females and to explore
      moderators of gender differences. The average, absolute difference between males
      and females across domains was relatively small (d = 0.21, SD = 0.14), with the
      majority of effects being either small (46%) or very small (39%). Magnitude of
      differences fluctuated somewhat as a function of the psychological domain (e.g.,
      cognitive variables, social and personality variables, well-being), but remained
      largely constant across age, culture, and generations. These findings provide
      compelling support for the gender similarities hypothesis, but also underscore
      conditions under which gender differences are most pronounced.

PMID- 25581006
TI  - A taxonomy for education and training in professional psychology health service
      specialties: evolution and implementation of new guidelines for a common
      language.
AB  - The Education and Training Guidelines: A Taxonomy for Education and Training in
      Professional Psychology Health Service Specialties was endorsed as a policy of
      the American Psychological Association in 2012. These Guidelines have the
      potential for broad impact on the field by providing both a structure and
      recommendations for the consistent usage of language--definitions and terminology
      -to reduce current descriptive inconsistencies across education and training
      programs in professional psychology. The Guidelines are not designed to define
      specifics of the training or practice of individual psychologists; they are to be
      used only to describe programmatic structure in a consistent manner. This article
      details the developmental history of these Guidelines and highlights the strong
      alliance between the leaders of the various recognized specialties in
      professional psychology and the education and training community in health
      service psychology. The content, application, future dissemination and impact of
      the Guidelines are presented.

PMID- 25581007
TI  - Guidelines for clinical supervision in health service psychology.
AB  - This document outlines guidelines for supervision of students in health service
      psychology education and training programs. The goal was to capture optimal
      performance expectations for psychologists who supervise. It is based on the
      premises that supervisors (a) strive to achieve competence in the provision of
      supervision and (b) employ a competency-based, meta-theoretical approach to the
      supervision process. The Guidelines on Supervision were developed as a resource
      to inform education and training regarding the implementation of competency-based
      supervision. The Guidelines on Supervision build on the robust literatures on
      competency-based education and clinical supervision. They are organized around
      seven domains: supervisor competence; diversity; relationships; professionalism;
      assessment/evaluation/feedback; problems of professional competence, and ethical,
      legal, and regulatory considerations. The Guidelines on Supervision represent the
      collective effort of a task force convened by the American Psychological
      Association (APA) Board of Educational Affairs (BEA).

PMID- 25581008
TI  - Henry Leland (1923-2013).
AB  - This article memorializes Henry Leland (1923-2013). Leland was an advocate for
      persons with intellectual and developmental disabilities (IDD). He was a skilled
      clinician and developmentalist, and his application of play therapy to affect
      specific outcomes in children with IDD was far ahead of its time. His legacy is
      reflected in the current Diagnostic and Statistical Manual of Mental Disorders
      (5th ed.) definition of IDD, in which severity levels are defined by a person's
      current adaptive capacities rather than their IQ scores. It is reflected in the
      fact that many states in the country have no institutions at all for persons with
      IDD because community living and working are now the standard. It is reflected in
      the social justice actions supporting persons with IDD in prisons and on death
      row. It is reflected in the empirically supported and widely accepted practices
      involving service delivery to young children with IDD and their families through
      use of play strategies.

PMID- 25581009
TI  - Rosa Anita Hagin (1921-2014).
AB  - This article memorializes Rosa Anita Hagin (1921-2014). Rosa's involvement with
      the American Psychological Association (APA) included associate member (1953),
      member (1958), fellow of Division 16 (School Psychology) and Division 37 (Child,
      Youth, and Family Services), and Division 16 secretary (1967-1970), Council
      Representative (1968-1971), and president (1971-1972). Rosa was a licensed
      psychologist, a diplomate in school psychology from the America Board of
      Professional Psychology, and served as president of the American Academy of
      School Psychology (1996-1997). Rosa received Division 16's Distinguished Service
      Award (1979), the Distinguished Achievement Award of the Learning Disabilities
      Association of American (1992), and the Orton Award from the International
      Dyslexia Association (1993). She was chosen to present the 2000 Legends Address
      for the National Association of School Psychologists. A professor with Fordham
      University-Lincoln Center's school psychology program since 1979, Rosa
      established the School Consultation Center, which was named in her honor after
      she retired and became professor emeritus in 1990. She continued her independent
      practice, researching the neuropsychology of learning disabilities, disseminating
      the Search and Teach (a program for the prevention of learning disabilities and
      their emotional consequences), consulting at a residential school for emotionally
      disturbed children, and serving as an expert witness in litigation on behalf of
      adults with learning disabilities.

PMID- 25581010
TI  - Donald Hugh Blocher (1928-2013).
AB  - This article memorializes Donald Hugh Blocher (1928-2013). Blocher, a giant in
      counseling psychology, was elected a fellow of the American Psychological
      Association (APA) in 1973, received a Distinguished Achievement Award from
      Harvard University in 1968, and served as president of APA Division 17 (Society
      of Counseling Psychology) in 1980. He obtained a Fulbright Lectureship at the
      University of Keele (United Kingdom) for 1968-1969, where he helped develop a
      counseling psychology program according to American standards. He also published
      many books, book chapters, and articles over the course of his professional
      career.

PMID- 25581011
TI  - Women's health providers: don't forget about polycystic ovary syndrome.
AB  - Comments on an article by Poleshuck and Woods (see record 2014-16756-003). The
      recent article by Poleshuck and Woods covered several areas of women's health
      that are defined, preceded, and/or followed by adverse psychosocial functioning.
      In a well-written and otherwise thorough summary of several women's health issues
      that are pertinent to mental health professionals, they neglected to mention
      polycystic ovary syndrome (PCOS), which is a very common disorder (8% to 17%
      prevalence; March et al., 2010) that is associated with several interrelated
      physiological and psychological disorders. The current author is submitting this
      comment because it is important that mental health professionals are familiar
      with the diagnostic criteria for PCOS, its impact on mental health functioning
      and on the development of several increasingly common chronic diseases, and how
      mental health professionals can play a role in reducing psychosocial disturbances
      and development of chronic disease among women with PCOS.

PMID- 25581012
TI  - Cucurbiturils as supramolecular inhibitors of DNA restriction by type II
      endonucleases.
AB  - Cucurbiturils (CB6 and CB7) were shown to inhibit the enzymatically catalyzed
      restriction of plasmids and linear DNA. This effect can be inverted by
      supramolecular masking of the macrocycles through competitive complexation with
      polyamines. These experiments provide supramolecular control of biocatalytic
      processes. 

PMID- 25581014
TI  - What is Hepatology looking for?

PMID- 25581013
TI  - Mean arterial pressure in the three trimesters of pregnancy: effects of maternal
      characteristics and medical history.
AB  - OBJECTIVE: To define the contribution of maternal variables that influence the
      measured mean arterial pressure (MAP) in screening for pregnancy complications.
      METHODS: Maternal characteristics and medical history were recorded, and MAP was
      measured, in women with a singleton pregnancy attending for three routine
      hospital visits at 11 + 0 to 13 + 6 weeks, 19 + 0 to 24 + 6 weeks and 30 + 0 to
      34 + 6 weeks or 35 + 0 to 37 + 6 weeks' gestation. For pregnancies delivering
      phenotypically normal live births or stillbirths at >= 24 weeks' gestation,
      variables from maternal demographic characteristics and medical history that are
      important in the prediction of MAP were determined from linear mixed-effects
      multiple regression analysis. RESULTS: MAP was measured in 75 841 cases in the
      first trimester, 30 447 in the second trimester and 31 673 in the third
      trimester. Significant independent contributions to MAP were provided by
      gestational age, maternal age, weight, height, Afro-Caribbean racial origin,
      cigarette smoking, family history of pre-eclampsia (PE), history of PE in the
      previous pregnancy, interpregnancy interval, chronic hypertension and diabetes
      mellitus. The effects of some variables were similar, and for others differed, in
      the three different trimesters. Random-effects multiple regression analysis was
      used to define the contribution of maternal variables that influence the measured
      MAP and express the values as multiples of the median (MoMs). The model was shown
      to provide an adequate fit of MoM values for all covariates, both in pregnancies
      that developed PE and in those without this complication. CONCLUSIONS: A model
      was fitted to express the measured MAP as MoMs after adjustment for variables
      from maternal characteristics and medical history that affect this measurement.

PMID- 25581015
TI  - Nb2O2F3: a reduced niobium (III/IV) oxyfluoride with a complex structural,
      magnetic, and electronic phase transition.
AB  - A new niobium oxyfluoride, Nb2O2F3, synthesized through the reaction of Nb, SnO,
      and SnF2 in Sn flux, within welded Nb containers, crystallizes in a monoclinic
      structure (space group: I2/a; a = 5.7048(1)A, b = 5.1610(1)A, c = 12.2285(2)A,
      beta = 95.751(1) degrees ). It features [Nb2X10] units (X = O, F), with short
      (2.5739(1) A) Nb-Nb bonds, that are linked through shared O/F vertices to form a
      3D structure configurationally isotypic to zeta-Nb2O5. Nb2O2F3 undergoes a
      structural transition at ~90 K to a triclinic structure (space group: P1; a =
      5.1791(5)A, b = 5.7043(6)A, c = 6.8911(7)A, alpha = 108.669(3) degrees , beta =
      109.922(2) degrees , gamma = 90.332(3) degrees ). The transition is described as
      a disproportionation or charge ordering of [Nb2](7+) dimers: (2[Nb2](7+) ->
      [Nb2](6+) + [Nb2](8+)), resulting in doubly (2.5000(9) A) and singly bonded
      (2.6560(9) A) Nb2 dimers. The structural transition is accompanied by an unusual
      field-independent "spin-gap-like" magnetic transition. 

PMID- 25581016
TI  - Microlandscaping of Au nanoparticles on few-layer MoS2 films for chemical
      sensing.
AB  - Surface modification or decoration of ultrathin MoS2 films with chemical moieties
      is appealing since nanointerfacing can functionalize MoS2 films with bonus
      potentials. In this work, a facile and effective method for microlandscaping of
      Au nanoparticles (NPs) on few-layer MoS2 films is developed. This approach first
      employs a focused laser beam to premodify the MoS2 films to achieve active
      surface domains with unbound sulfur. When the activated surface is subsequently
      immersed in AuCl3 solution, Au NPs are found to preferentially decorate onto the
      modified regions. As a result, Au NPs can be selectively and locally anchored
      onto designated regions on the MoS2 surface. With a scanning laser beam,
      microlandscapes comprising of Au NPs decorated on laser-defined micropatterns are
      constructed. By varying the laser power, reaction time and thickness of the MoS2
      films, the size and density of the NPs can be controlled. The resulting hybrid
      materials are demonstrated as efficient Raman active surfaces for the detection
      of aromatic molecules with high sensitivity. 

PMID- 25581018
TI  - Brief report: successful in vitro culture of rheumatoid arthritis synovial tissue
      explants at the air-liquid interface.
AB  - OBJECTIVE: To establish a method to culture synovial tissue explants from
      patients with rheumatoid arthritis (RA). METHODS: Synovial tissue explants
      obtained from 10 patients with RA were cultured at the air-liquid interface or
      were submerged in culture medium. As a control, synovial explants were engrafted
      subcutaneously into SCID mice. The synovial explants were harvested at different
      time points, and histologic or flow cytometric analysis was performed. Cytokine
      levels in the culture supernatants were measured by enzyme-linked immunosorbent
      assay. Infliximab was added to the air-liquid interface culture to evaluate the
      effect of tumor necrosis factor alpha blockade on inflammatory cytokine
      production. RESULTS: The histologic features of RA synovitis, including a
      hyperplastic lining layer and the presence of cellular infiltrate in the
      sublining layer, were maintained in synovial tissue explants in air-liquid
      interface culture. In synovial grafts harvested from SCID-HuRAg mice, the
      cellular infiltrate was well maintained in the sublining, but the lining layer
      was lost. Viable CD4+ T cells and macrophages were abundant after air-liquid
      interface culture but were virtually absent after submerged culture. Furthermore,
      synovial tissue explants in air-liquid interface culture produced interleukin-6
      (IL-6) and IL-8 for a prolonged period of time. The addition of infliximab
      effectively reduced cytokine production. CONCLUSION: RA synovial explants can be
      maintained for weeks using an air-liquid interface culture. This simple culture
      system might be useful for analyzing the pathogenesis of RA synovitis and for
      developing antirheumatic drugs.

PMID- 25581017
TI  - Discovery of small molecule inhibitors to Kruppel-like factor 10 (KLF10):
      implications for modulation of T regulatory cell differentiation.
AB  - The Kruppel-like family of transcription factors (KLFs) constitute a subfamily of
      C2H2-type zinc finger proteins with distinct cell-type expression patterns and
      regulate functional aspects of cell growth and differentiation, activation, or
      development. KLF10 has been previously shown to critically regulate the
      acquisition of CD4+CD25+ T regulatory cell differentiation and function, an
      effect important to the maintenance of self-tolerance, immune suppression, and
      tumor immunosurveillance. To date, there are no selective pharmacological
      inhibitors to KLF10. Herein, we report on the discovery of first-in-class small
      molecule compounds that inhibit the KLF10-DNA interaction interface using
      computer-aided drug design (CADD) screens of chemical libraries. Interrogation of
      a "druggable" pocket in the second zinc finger of KLF10 revealed three small
      molecules, #48, #48-15, and #15-09, with similar scaffolds and binding patterns.
      Each of these small molecules inhibited KLF10-DNA binding and transcriptional
      activity, conversion of CD4+CD25- T cells to CD4+CD25+ T regulatory cells, and
      KLF10 target gene expression. Taken together, these findings support the
      feasibility of using CADD with functional assays to identify small molecules that
      target members of the KLF subfamily of transcription factors to regulate
      biological functions in health and disease. We hope these novel compounds will
      serve as useful mechanistic probes for KLF10-mediated effects and T regulatory
      cell biology. 

PMID- 25581019
TI  - Self-assembled chiral nanofibers from ultrathin low-dimensional nanomaterials.
AB  - Despite many developed methods, it still remains a challenge to provide a simple
      and general strategy for the controlled preparation of chiral nanostructures.
      Here we report a facile and universal approach for the high-yield and scalable
      preparation of chiral nanofibers based on the self-assembly of various ultrathin
      one-dimensional and two-dimensional nanomaterials in vigorously stirred polymeric
      solutions. The obtained chiral nanofibers can be further transformed to same
      handed chiral nanorings. As a proof-of-concept application, chiral MoS(2) and
      multiwalled carbon nanotube nanofibers were used as promising active layers for
      flexible nonvolatile data storage devices. Impressively, the chiral MoS(2)
      nanofiber-based memory device presents a typical nonvolatile flash memory effect
      with excellent reproducibility and good stability. Our method offers a general
      route for the preparation of various functional chiral nanostructures that might
      have wide applications.

PMID- 25581022
TI  - On copper(I) fluorides, the cuprophilic interaction, the preparation of copper
      nitride at room temperature, and the formation mechanism at elevated
      temperatures.
AB  - Our attempts to synthesize the hitherto unknown binary copper(I) fluoride have
      led to first successes and a serendipitious result: By conproportionation of
      elemental copper and copper(II) fluoride in anhydrous liquid ammonia, two
      copper(I) fluorides were obtained as simple NH3 complexes. One of them presents
      an example of ligand-unsupported "cuprophilic" interactions in an infinite [Cu2
      (NH3 )4 ](2+) chain with alternating Cu-Cu distances. We discovered that both
      copper(I) fluorides can easily be converted into Cu3 N at room temperature, just
      by applying a vacuum. Additionally, we investigated the formation mechanism of
      the classical synthesis route of Cu3 N that starts with CuF2 and flowing NH3 in
      the temperature range between ambient and 290  degrees C by means of thermal
      analysis and in situ neutron diffraction. The reaction proceeds at elevated
      temperatures through the formation of a blue and amorphous ammoniate Cu(NH3 )2 F2
      , the reformation of CuF2 , and finally the redox reaction to form Cu3 N. 

PMID- 25581023
TI  - Cancer screening in the United States, 2015: a review of current American cancer
      society guidelines and current issues in cancer screening.
AB  - Each year, the American Cancer Society (ACS) publishes a summary of its
      guidelines for early cancer detection along with a report on data and trends in
      cancer screening rates and select issues related to cancer screening. In this
      issue of the journal, we summarize current ACS cancer screening guidelines. The
      latest data on utilization of cancer screening from the National Health Interview
      Survey (NHIS) also is described, as are several issues related to screening
      coverage under the Affordable Care Act, including the expansion of the Medicaid
      program.

PMID- 25581024
TI  - Nanogels for delivery, imaging and therapy.
AB  - Nanogels are hydrogels having size in nanoregime, which is composed of cross
      linked polymer networks. The advantages of nanogels include stimuli-responsive
      nature, easy drug loading, and higher drug-loading capacity, physical stability,
      versatility in design, stability of entrapped drug, and controlled release of the
      anti-inflammatory, antimicrobial, protein, peptide and anticancer drugs. Stimuli
      responsive nature of nanogel is of particular importance in anticancer and anti
      inflammatory drug delivery, as cancer and inflammation are associated with acidic
      pH, heat generation, and change in ionic content. Nanogels composed of muco
      adhesive polymers provide prolonged residence time and increase the ocular
      availability of loaded drugs. By forming suitably sized complex with proteins or
      by acting as artificial chaperones, they thus help to keep the proteins and
      enzymes in proper confirmation necessary for exerting biological activity;
      nanogels can increase the stability and activity of protein/peptide drugs. Better
      drug penetrations achieved by prolonged contact with skin contribute much in
      transdermal drug delivery. When it comes to cancer drug delivery, the presence of
      multiple interactive functional groups in nanogels different targeting agents can
      be conjugated for delivery of the selective drugs. This review focuses on
      applications of nanogels in cancer drug delivery and imaging, anti-inflammatory,
      anti-psoriatic, transdermal, ocular and protein/peptide drug delivery and
      therapy.

PMID- 25581025
TI  - Hodgkin transformation of chronic lymphocytic leukemia: Incidence, outcomes, and
      comparison to de novo Hodgkin lymphoma.
AB  - Although transformation to Hodgkin lymphoma (HL) is a recognized complication in
      patients with chronic lymphocytic leukemia (CLL), its incidence, clinical
      characteristics and outcomes are not well defined. We used the Mayo Clinic CLL
      and Lymphoma Databases to identify CLL patients who developed biopsy-proven HL
      (CLL/HL) on follow-up, as well as cases of de novo HL (i.e., without prior CLL).
      Among 3887 CLL patients seen at Mayo Clinic from January 1995 through August
      2011, 26 (0.7%) developed HL. In a nested cohort of 2,465 newly diagnosed CLL
      patients followed prospectively, the incidence of HL was 0.05%/year (10 year risk
      = 0.5%). The median overall survival (OS) from date of HL diagnosis in patients
      with CLL/HL was 3.9 years compared to not reached for de novo HL patients (n =
      709) seen during the same time interval (P < 0.001). The shorter OS of CLL/HL
      patients persisted after adjusting for differences in age and Ann Arbor stage of
      disease. The International Prognostic score (IPS) developed for de novo HL
      stratified prognosis among CLL/HL patients with median survival of not reached,
      6.2, 2.4, and 0.3 years (P = 0.006) for those with IPS scores of <=2, 3, 4, and
      >=5, respectively. In summary, approximately 1 of every 200 CLL patients will
      develop HL within 10 years. Survival after HL diagnosis in patients with CLL is
      shorter than de novo HL patients. The IPS for de novo HL may be useful for
      stratifying survival in CLL/HL patients.

PMID- 25581027
TI  - High-throughput salting-out-assisted liquid-liquid extraction for the
      simultaneous determination of atorvastatin, ortho-hydroxyatorvastatin, and para
      hydroxyatorvastatin in human plasma using ultrafast liquid chromatography with
      tandem mass spectrometry.
AB  - A high-throughput, specific, and rapid liquid chromatography with tandem mass
      spectrometry method was established and validated for the simultaneous
      determination of atorvastatin and its two major metabolites, ortho
      hydroxyatorvastatin and para-hydroxyatorvastatin, in human plasma. A simple
      salting-out-assisted liquid-liquid extraction using acetonitrile and a mass
      spectrometry-friendly salt, ammonium acetate, was employed to extract the
      analytes from human plasma. A recovery of more than 81% for all analytes was
      achieved in 1 min extraction time. Chromatographic separation was performed on a
      Kinetex XB C18 column utilizing a gradient elution starting with a 60% of water
      solution (1% formic acid), followed by increasing percentages of acetonitrile.
      Analytes were detected on a tandem mass spectrometer equipped with an
      electrospray ionization source that was operated in the positive mode, using the
      transitions of m/z 559.3 -> m/z 440.2 for atorvastatin, and m/z 575.3 -> m/z
      440.2 for both ortho- and para-hydroxyatorvastatin. Deuterium-labeled compounds
      were used as the internal standards. The method was validated over the
      concentration ranges of 0.0200-15.0 ng/mL for atorvastatin and ortho
      hydroxyatorvastatin, and 0.0100-2.00 ng/mL for para-hydroxyatorvastatin with
      acceptable accuracy and precision. It was then successfully applied in a
      bioequivalence study of atorvastatin. 

PMID- 25581028
TI  - Clinical documentation in the 21st century: executive summary of a policy
      position paper from the American College of Physicians.
AB  - Clinical documentation was developed to track a patient's condition and
      communicate the author's actions and thoughts to other members of the care team.
      Over time, other stakeholders have placed additional requirements on the clinical
      documentation process for purposes other than direct care of the patient. More
      recently, new information technologies, such as electronic health record (EHR)
      systems, have led to further changes in the clinical documentation process.
      Although computers and EHRs can facilitate and even improve clinical
      documentation, their use can also add complexities; new challenges; and, in the
      eyes of some, an increase in inappropriate or even fraudulent documentation. At
      the same time, many physicians and other health care professionals have argued
      that the quality of the systems being used for clinical documentation is
      inadequate. The Medical Informatics Committee of the American College of
      Physicians has undertaken this review of clinical documentation in an effort to
      clarify the broad range of complex and interrelated issues surrounding clinical
      documentation and to suggest a path forward such that care and clinical
      documentation in the 21st century best serve the needs of patients and families. 

PMID- 25581026
TI  - Members of the chloride intracellular ion channel protein family demonstrate
      glutaredoxin-like enzymatic activity.
AB  - The Chloride Intracellular Ion Channel (CLIC) family consists of six
      evolutionarily conserved proteins in humans. Members of this family are unusual,
      existing as both monomeric soluble proteins and as integral membrane proteins
      where they function as chloride selective ion channels, however no function has
      previously been assigned to their soluble form. Structural studies have shown
      that in the soluble form, CLIC proteins adopt a glutathione S-transferase (GST)
      fold, however, they have an active site with a conserved glutaredoxin monothiol
      motif, similar to the omega class GSTs. We demonstrate that CLIC proteins have
      glutaredoxin-like glutathione-dependent oxidoreductase enzymatic activity. CLICs
      1, 2 and 4 demonstrate typical glutaredoxin-like activity using 2-hydroxyethyl
      disulfide as a substrate. Mutagenesis experiments identify cysteine 24 as the
      catalytic cysteine residue in CLIC1, which is consistent with its structure.
      CLIC1 was shown to reduce sodium selenite and dehydroascorbate in a glutathione
      dependent manner. Previous electrophysiological studies have shown that the drugs
      IAA-94 and A9C specifically block CLIC channel activity. These same compounds
      inhibit CLIC1 oxidoreductase activity. This work for the first time assigns a
      functional activity to the soluble form of the CLIC proteins. Our results
      demonstrate that the soluble form of the CLIC proteins has an enzymatic activity
      that is distinct from the channel activity of their integral membrane form. This
      CLIC enzymatic activity may be important for protecting the intracellular
      environment against oxidation. It is also likely that this enzymatic activity
      regulates the CLIC ion channel function. 

PMID- 25581029
TI  - Nutrient and mineral composition during shoot growth in seven species of
      Phyllostachys and Pseudosasa bamboo consumed by giant panda.
AB  - During the annual period of bamboo shoot growth in spring, free-ranging giant
      pandas feed almost exclusively on the shoots while ignoring the leaves and full-
      height culm. Little is known about the nutritional changes that occur during
      bamboo shoot growth, if nutritional changes differ among species, or how these
      changes might influence forage selection. Our objective was to examine the
      nutrient and mineral composition during three phases of shoot growth (<60, 90-150
      and >180 cm) for seven species of bamboo (Phyllostachys (P.) aurea, P.
      aureosulcata, P. bissetii, P. glauca, P. nuda, P. rubromarginata, Pseudosasa
      japonica) fed to captive giant pandas at the Memphis Zoo. Total dietary fiber
      content of bamboo shoots increased (p < 0.0001) from an overall species average
      of 61% dry matter (DM) at < 60 cm to 75% DM at shoot heights > 180 cm, while
      crude protein, fat and ash exhibited significant declines (p < 0.05).
      Phyllostachys nuda had the overall greatest (p = 0.007) crude protein (21% DM)
      and fat (4% DM) content, and lowest overall total fibre (61% DM) content compared
      to the other species examined. In contrast, Pseudosasa japonica had the overall
      lowest crude protein and fat, and relatively higher fibre content (9%, 3% and 74%
      respectively). Concentrations of Zn and Fe were highest in shoots <60 cm (10-50
      MUg/g DM) and decreased (p < 0.05) during growth in all species examined.
      Concentrations of Ca, Cu, Mn, Na and K varied among species and were largely
      unaffected by growth stage. Due to their higher concentrations of nutrients and
      lower fibre content in comparison to culm and leaf, bamboo shoots should be a
      major component of captive giant panda diets when available.

PMID- 25581031
TI  - ICE1 demethylation drives the range expansion of a plant invader through cold
      tolerance divergence.
AB  - Cold tolerance adaption is a crucial determinant for the establishment and
      expansion of invasive alien plants into new cold environments; however, its
      evolutionary mechanism is poorly understood. Crofton weed (Ageratina adenophora),
      a highly invasive alien plant, is continuously spreading across subtropical areas
      in China, north-eastward from the first colonized south-western tropical regions,
      through cold tolerance evolution. Close relations between the cold tolerance
      levels of 34 populations, represented by 147 accessions, and the latitude,
      extreme lowest temperature, coldest month average temperature, and invasion
      period have provided direct insight into its cold tolerance divergence. A
      comparative study of the CBF pathway, associated with the cold tolerance
      enhancement of cold-susceptible CBF1-transgenic plant, among four geographically
      distinct crofton weed populations revealed that the CBF pathway plays a key role
      in the observed cold tolerance divergence. Four epialleles of the cold response
      regulator ICE1 ranged from 66 to 50 methylated cytosines, representing a 4.4% to
      3.3% methylation rate and significantly corresponding to the lowest to highest
      cold tolerance levels among these different populations. The significant negative
      relation between the transcription levels of the primary CBF pathway members,
      except for CBF2, and the methylation levels among the four populations firstly
      demonstrates that the demethylation-upregulated transcription level of CBF
      pathway is responsible for this evolution. These facts, combined with the cold
      tolerance variation and methylation found among three native and two other
      introduced populations, indicate that the ICE1-demethylated upregulation of cold
      tolerance may be the underlying evolutionary mechanism allowing crofton weed to
      expand northward in China. 

PMID- 25581032
TI  - Ferroelectric polymer nanocomposites for room-temperature electrocaloric
      refrigeration.
AB  - Solution-processable ferroelectric polymer nanocomposites are developed as a new
      form of electrocaloric materials that can be effectively operated under both
      modest and high electric fields at ambient temperature. By integrating the
      complementary properties of the constituents, the nanocomposites exhibit state-of
      the-art cooling energy densities. Greatly improved thermal conductivity also
      yields superior cooling power densities validated by finite volume simulations. 

PMID- 25581030
TI  - The DNA-binding network of Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis (MTB) infects 30% of all humans and kills someone
      every 20-30 s. Here we report genome-wide binding for ~80% of all predicted MTB
      transcription factors (TFs), and assayed global expression following induction of
      each TF. The MTB DNA-binding network consists of ~16,000 binding events from 154
      TFs. We identify >50 TF-DNA consensus motifs and >1,150 promoter-binding events
      directly associated with proximal gene regulation. An additional ~4,200 binding
      events are in promoter windows and represent strong candidates for direct
      transcriptional regulation under appropriate environmental conditions. However,
      we also identify >10,000 'dormant' DNA-binding events that cannot be linked
      directly with proximal transcriptional control, suggesting that widespread DNA
      binding may be a common feature that should be considered when developing global
      models of coordinated gene expression.

PMID- 25581034
TI  - Omega-3 polyunsaturated fatty acids and chronic obstructive pulmonary disease.
AB  - PURPOSE OF REVIEW: The aim of the present review was to summarize recent research
      developments relating omega-3 polyunsaturated fatty acids (PUFAs) and chronic
      obstructive pulmonary disease (COPD). RECENT FINDINGS: COPD is a chronic
      inflammatory disease; hence, omega-3 PUFAs may have beneficial effects. At
      present, however, there are limited data available regarding the potential for
      omega-3 PUFAs to be used therapeutically in COPD. In 2012-2013, several
      observational studies have emerged, which demonstrate that circulating omega-3
      PUFA levels in COPD are inversely associated with systemic inflammation and
      positively associated with clinical outcomes. To date, all interventions
      incorporating omega-3 PUFAs in COPD have used nutrient combinations, such that
      the specific effects of omega-3 PUFAs cannot be determined. Three clinical trials
      in COPD are underway, which use therapeutic doses of omega-3 PUFAs alone, with
      positive results beginning to emerge in 2014. SUMMARY: Observational data support
      the hypothesis that omega-3 PUFAs may provide a therapeutic strategy for managing
      COPD. Several intervention trials using omega-3 PUFAs in COPD are underway, which
      will provide a substantive amount of new data to inform the field and allow
      evidence-based advice to be generated for patients with COPD in the near future.

PMID- 25581033
TI  - Heart failure and dementia: survival in relation to types of heart failure and
      different dementia disorders.
AB  - AIMS: Heart failure (HF) and dementia frequently coexist, but little is known
      about their types, relationships to each other and prognosis. The aims were to
      (i) describe patients with HF and dementia, assess (ii) the proportion of
      specific dementia disorders in types of HF based on ejection fraction and (iii)
      the prognostic role of types of HF and dementia disorders. METHODS AND RESULTS:
      The Swedish Heart Failure Registry (RiksSvikt) and The Swedish Dementia Registry
      (SveDem) were record-linked. Associations between dementia disorders and HF types
      were assessed with multinomial logistic regression and survival was investigated
      with Kaplan-Meier analysis and multivariable Cox regression. We studied 775
      patients found in both registries (55% men, mean age 82 years). Ejection fraction
      was preserved in 38% of patients, reduced in 34%, and missing in 28%. The
      proportions of dementia disorders were similar across HF types. Vascular dementia
      was the most common dementia disorder (36%), followed by other dementias (28%),
      mixed dementia (20%), and Alzheimer disease (16%). Over a mean follow-up of 1.5
      years, 76% of patients survived 1 year. We observed no significant differences in
      survival with regard to HF type (P = 0.2) or dementia disorder (P = 0.5). After
      adjustment for baseline covariates, neither HF types nor dementia disorders were
      independently associated with survival. CONCLUSIONS: Heart failure with preserved
      ejection fraction was the most common HF type and vascular dementia was the most
      common dementia disorder. The proportions of dementia disorders were similar
      across HF types. Neither HF types nor specific dementia disorders were associated
      with survival.

PMID- 25581035
TI  - Current evidence and future directions for research with omega-3 fatty acids and
      attention deficit hyperactivity disorder.
AB  - PURPOSE OF REVIEW: Nutritional insufficiencies of nutrients such as omega-3
      highly unsaturated fatty acids (HUFAs), vitamins and minerals have been linked to
      suboptimal developmental outcomes including attention deficit hyperactivity
      disorder (ADHD). Although the predominant treatment is currently psychostimulant
      medications, randomized clinical trials with omega-3 HUFAs have reported small-to
      modest effects in reducing symptoms of ADHD in children despite arguable
      individual methodological and design misgivings. RECENT FINDINGS: This review
      presents, discusses and critically evaluates data and findings from meta-analytic
      and systematic reviews and clinical trials published within the last 12 months.
      Recent trajectories of this research are discussed, such as comparing
      eicosapentaenoic acid and docosahexaenoic acid and testing the efficacy of omega
      3 HUFAs as an adjunct to methylphenidate. Discussion includes highlighting
      limitations and potential future directions such as addressing variable findings
      by accounting for other nutritional deficiencies and behavioural food
      intolerances. SUMMARY: The authors conclude that given the current economic
      burden of ADHD, estimated in the region of $77 billion in the USA alone, in
      addition to the fact that a proportion of patients with ADHD are either treatment
      resistant, nonresponders or withdraw from medication because of adverse side
      effects, the investigation of nonpharmacological interventions including omega-3
      HUFAs in clinical practice warrants extrapolating.

PMID- 25581036
TI  - Structure-function relationship of the milk fat globule.
AB  - PURPOSE OF REVIEW: The complex biochemical composition and physical structure of
      the milk fat globule (MFG) are presented as a basis for its paradoxical metabolic
      fate: MFG is a rapid conveyor of energy through its triacylglycerol (TAG) core
      but contains some low-digestible bioactive complex lipids and proteins, which
      influence lipid metabolism and contribute to intestinal and systemic health.
      RECENT FINDINGS: MFG structure modulates gastrointestinal lipolysis, postprandial
      lipemia and even the postprandial fate of ingested fatty acids. Proof-of-concept
      of the nutritional programming induced by early consumption of an emulsion
      biomimetic of MFG compared with a typical infant formula was published in an
      animal model (mice). The metabolic response to a high-fat diet during adulthood
      was improved following neonatal exposure to the biomimetic emulsion. SUMMARY: MFG
      TAG are tailored with a unique regiodistribution delivering in priority short to
      medium-chain fatty acids in gastric phase, an important amount of quickly
      metabolizable oleic acid and protecting palmitic acid in sn-2 position. MFG
      digestion may not only trigger rapid TAG and chylomicron plasma peaks with fast
      clearance but also the luminal release of nonhydrolysable bioactive compounds
      (glycosylated compounds and sphingomyelin), which contribute to intestinal and
      systemic health by shaping the microbiota and modulating the immune system. These
      bioactive compounds form self-assembled structures, protect specific
      micronutrients and lower cholesterol absorption. The health benefits of MFG
      consumption or of some of its fractions (MFGM) under specific structures are
      steadily being demonstrated with still much unsolved questions especially for
      populations with high nutritional needs (e.g. elderly, infants).

PMID- 25581037
TI  - Early fatty acid exposure and later obesity risk.
AB  - PURPOSE OF REVIEW: The impact of fatty acids in early nutrition on later body
      composition and obesity risk remains elusive. Aim of this review was to summarize
      and discuss recent studies on the role of early supply with long-chain
      polyunsaturated fatty acids (LCPUFAs) through maternal nutrition during pregnancy
      and lactation for later offspring obesity. RECENT FINDINGS: Recent human studies,
      either interventional or observational, investigating the role of dietary fatty
      acids, in particular of LCPUFAs, on body composition and later obesity risk
      provide inconsistent results concerning BMI as well as fat mass development in
      the offspring. A recent meta-analysis of randomized controlled trials found no
      significant effect of maternal supplementation with n-3 LCPUFA on BMI in both
      preschool and school-aged children. SUMMARY: There is currently no conclusive
      evidence that dietary intervention to modify fat intake during pregnancy and
      lactation is a reasonable strategy to prevent childhood obesity in humans, but
      more research is clearly needed to address this issue.

PMID- 25581039
TI  - Frequency and pattern of central lymph node metastasis in papillary carcinoma of
      the thyroid isthmus.
AB  - BACKGROUND: The purpose of this study was to evaluate the frequency and pattern
      of central lymph node metastasis in isthmic papillary thyroid carcinoma (PTC).
      METHODS: We compared the clinical and pathological data of 45 patients with a
      single isthmic PTC and 149 patients with a single PTC located in the unilateral
      thyroid lobe, all of whom underwent total thyroidectomy and bilateral central
      neck dissection. RESULTS: The rates of clinical, pathologic, and occult central
      lymph node metastasis were higher in the isthmus group than the non-isthmus
      group. Central lymph node metastasis in the pretracheal and bilateral
      paratracheal lymph nodes was more frequent in the isthmic PTC group than in the
      non-isthmus group. On multivariate analysis, isthmic location of the tumor was an
      independent risk factor for central lymph node metastasis. CONCLUSION: Complete
      bilateral central neck dissection should be considered for isthmic PTC because of
      the high rate of bilateral central lymph node metastasis, especially to
      pretracheal and bilateral paratracheal lymph nodes. (c) 2015 Wiley Periodicals,
      Inc. Head Neck 38: E412-E416, 2016.

PMID- 25581038
TI  - Nontuberculous mycobacterial ocular infections--comparing the clinical and
      microbiological characteristics between Mycobacterium abscessus and Mycobacterium
      massiliense.
AB  - PURPOSE: To analyze the clinical characteristics of nontuberculous mycobacterial
      (NTM) ocular infections and the species-specific in vitro antimicrobial
      susceptibility. MATERIAL AND METHODS: In 2000 to 2011 at the National Taiwan
      University Hospital, multilocus sequencing of rpoB, hsp65 and secA was used to
      identify NTM isolates from ocular infections. The clinical presentation and
      treatment outcomes were retrospectively compared between species. Broth
      microdilution method was used to determine the minimum inhibitory concentrations
      of amikacin (AMK), clarithromycin (CLA), ciprofloxacin (CPF), levofloxacin (LVF),
      moxifloxacin (MXF) and gatifloxacin (GAF) against all strains. The activities of
      antimicrobial combinations were assessed by the checkerboard titration method.
      RESULTS: A total of 24 NTM strains (13 Mycobacterium abscessus and 11
      Mycobacterium massiliense) were isolated from 13 keratitis, 10 buckle infections,
      and 1 canaliculitis cases. Clinically, manifestations and outcomes caused by
      these two species were similar and surgical intervention was necessary for
      medically unresponsive NTM infection. Microbiologically, 100% of M. abscessus and
      90.9% of M. massiliense ocular isolates were susceptible to amikacin but all were
      resistant to fluoroquinolones. Inducible clarithromycin resistance existed in
      69.3% of M. abscessus but not in M. massiliense isolates. None of the AMK-CLA,
      AMK-MXF, AMK-GAF, CLA-MXF and CLA-GAF combinations showed synergistic or
      antagonistic effect against both species in vitro. CONCLUSIONS: M. abscessus and
      M. massiliense are the most commonly identified species for NTM ocular infections
      in Taiwan. Both species were resistant to fluoroquinolones, susceptible to
      amikacin, and differ in clarithromycin resistance. Combined antimicrobial
      treatments showed no interaction in vitro but could be considered in combination
      with surgical interventions for eradication of this devastating ocular infection.

PMID- 25581040
TI  - Corrigendum: Protruding knob-like proteins violate local symmetries in an
      icosahedral marine virus.

PMID- 25581041
TI  - Agronomic Practices for Improving Gentle Remediation of Trace Element
      Contaminated Soils.
AB  - The last few decades have seen the rise of Gentle soil Remediation Options (GRO),
      which notably include in situ contaminant stabilization ("inactivation") and
      plant-based (generally termed "phytoremediation") options. For trace element (TE)
      contaminated sites, GRO aim to either decrease their labile pool and/or total
      content in the soil, thereby reducing related pollutant linkages. Much research
      has been dedicated to the screening and selection of TE-tolerant plant species
      and genotypes for application in GRO. However, the number of field trials
      demonstrating successful GRO remains well below the number of studies carried out
      at a greenhouse level. The move from greenhouse to field conditions requires
      incorporating agronomical knowledge into the remediation process and the
      ecological restoration of ecosystem services. This review summarizes agronomic
      practices against their demonstrated or potential positive effect on GRO
      performance, including plant selection, soil management practices, crop rotation,
      short rotation coppice, intercropping/row cropping, planting methods and plant
      densities, harvest and fertilization management, pest and weed control and
      irrigation management. Potentially negative effects of GRO, e.g., the
      introduction of potentially invasive species, are also discussed. Lessons learnt
      from long-term European field case sites are given for aiding the choice of
      appropriate management practices and plant species. 

PMID- 25581042
TI  - Intestinal gas homeostasis: disposal pathways.
AB  - BACKGROUND: Patients with functional gut disorders frequently complain of gas
      related symptoms, but the role of intestinal gas in this context is not clear,
      because intestinal gas homeostasis is incompletely understood. Our aim was to
      compare the proportion of the gas produced by colonic fermentation that is
      evacuated per anus and that eliminated via alternative pathways. METHODS: In 20
      healthy subjects, gas evacuated per anus was collected for 4 h after a standard
      flatulogenic test meal. Paired studies were performed without and with high-rate
      infusion of exogenous gas (24 mL/min) into the jejunum to wash-out of the gut the
      endogenous gas produced by bacterial fermentation. The exogenous gas infused was
      labeled (5% SF6) to calculate the proportion of endogenous gas evacuated. KEY
      RESULTS: In the experiments with gaseous wash-out, 1817 +/- 139 mL of endogenous
      gas was produced over the 4-h study period. However, in the experiments without
      wash-out (basal conditions), 376 +/- 43 mL were evacuated, indicating that only
      23 +/- 3% of the gas produced was finally eliminated per anus, while the rest (77
      +/- 3%) had been previously eliminated via alternative pathways. CONCLUSIONS &
      INFERENCES: Intestinal gas homeostasis is a highly dynamic process by which a
      large proportion of the gas produced by bacterial fermentation of meal residues
      is rapidly absorbed into the blood and/or metabolized by gas-consuming
      microorganisms, and only a relatively modest proportion is eliminated per anus.
      These data contribute to clarify the complex dynamics of intestinal gas and may
      help interpret the pathophysiology of gas-related symptoms.

PMID- 25581043
TI  - [A Very Rare and Easily Missed Macular Disease].

PMID- 25581044
TI  - [Growth Factors and Interleukins in Amniotic Membrane Tissue Homogenate].
AB  - PURPOSE: Application of amniotic membrane homogenate eye drops may be a potential
      treatment alternative for therapy resistant corneal epithelial defects. The
      purpose of this study was to determine the concentrations of epidermal growth
      factor (EGF), fibroblast growth factor basic (bFGF), hepatocyte growth factor
      (HGF), keratinocyte growth factor (KGF), interleukin-6 (IL-6) and interleukin-8
      (IL-8) in amniotic membrane homogenates. METHODS: Amniotic membranes of 8
      placentas were prepared and thereafter stored at - 80  degrees C using the
      standard methods of the LIONS Cornea Bank Saar-Lor-Lux, Trier/Westpfalz.
      Following defreezing, amniotic membranes were cut in two pieces and homogenized
      in liquid nitrogen. One part of the homogenate was prepared in cell-lysis buffer,
      the other part was prepared in PBS. The tissue homogenates were stored at - 20 
      degrees C until enzyme-linked immunosorbent assay (ELISA) analysis for EGF, bFGF,
      HGF, KGF, IL-6 and IL-8 concentrations. RESULTS: Concentrations of KGF, IL-6 and
      IL-8 were below the detection limit using both preparation techniques. The EGF
      concentration in tissue homogenates treated with cell-lysis buffer (2412 pg/g
      tissue) was not significantly different compared to that of tissue homogenates
      treated with PBS (1586 pg/g tissue, p = 0.72). bFGF release was also not
      significantly different using cell-lysis buffer (3606 pg/g tissue) or PBS treated
      tissue homogenates (4649 pg/g tissue, p = 0.35). HGF release was significantly
      lower using cell-lysis buffer (23,555 pg/g tissue), compared to PBS treated
      tissue (47,766 pg/g tissue, p = 0.007). CONCLUSION: Containing EGF, bFGF and HGF,
      and lacking IL-6 and IL-8, the application of amniotic membrane homogenate eye
      drops may be a potential treatment alternative for therapy-resistant corneal
      epithelial defects.

PMID- 25581045
TI  - [Central retinal vein: its pulsation and pressure in glaucoma].
AB  - BACKGROUND: The ocular perfusion pressure (PP) is presently calculated by
      subtracting the intraocular pressure (IOP) from the mean ophthalmic artery
      pressure. In recent years papers have been published in which it has been shown
      that the pressure in the central retinal vein (CRV) may be higher than the IOP in
      half the glaucoma patients resulting in a lower perfusion pressure in the retina
      and in the prelaminar layer of the optic nerve head. OBJECTIVES: A review of
      these papers is given in which the pulsation of the CRV was assessed or in which
      the pressure in the CRV has been measured on comparing glaucoma patients and
      control subjects. MATERIALS AND METHODS: By using the Starling resistor as a
      model the origin of the pulsation of the CRV is explained. The term
      ophthalmodynamometric force used by Morgan et al. is shown as being the IOP
      increment given in units of gram-force which may be converted to 0.82 mmHg.
      Contact lens dynamometry is described. RESULTS: In the five studies published
      until now the pulsation of the central retinal vein was absent in about half of
      the glaucoma patients. That is the sign that the pressure in the CRV was higher
      than the IOP. A worse mean deviation has been found to be strongly predictive of
      a higher pressure in the CRV. Higher pressures in upper and lower hemiveins were
      strongly associated with a worse mean deviation in the corresponding hemifields.
      In the two studies in which the CRV pressure has been measured in mmHg it was up
      to 25 mmHg higher in the median than the IOP. A Long-term study of 82 months has
      shown that the pressure in the central retinal vein is strongly predictive of an
      increase of optic disc excavation. CONCLUSIONS: The CRV pressure is often higher
      in glaucoma patients resulting in a lower PP than assumed until now.

PMID- 25581046
TI  - Microbial diversity of the supra- and subgingival biofilm of healthy individuals
      after brushing with chlorhexidine- or silver-coated toothbrush bristles.
AB  - Nanoparticulate silver has recently been reported as an effective antimicrobial
      agent. The aim of this clinical study was to investigate the potential changes on
      the oral microbiota of healthy individuals after controlled brushing with
      chlorhexidine- or silver-coated toothbrush bristles. Twenty-four healthy
      participants were enrolled in this investigation and randomly submitted to 3
      interventions. All the participants received, in a crossover format, the
      following toothbrushing interventions: (i) chlorhexidine-coated bristles, (ii)
      silver-coated bristles, and (iii) conventional toothbrush (Control). All the
      interventions had a duration of 30 days. The DNA checkerboard hybridization
      method was used to identify and quantify up to 43 microbial species colonizing
      the supra- and subgingival biofilm. The supragingival samples presented higher
      genome counts than the subgingival samples (p < 0.0001). The total genome counts
      from the Control group showed the highest values, followed by the silver and
      chlorhexidine groups (p < 0.0001). After 4 weeks of brushing, the silver-coated
      and chlorhexidine-coated bristles were capable of reducing or maintaining lower
      levels of the bacterial counts of the putative periodontal pathogens Tanerella
      forsythia, Treponema denticola, and Porphyromonas gingivalis. Other major
      periodontal pathogens, such as Prevotella intermedia, Fusobacterium nucleatum,
      Prevotella nigrescens, and Parvimonas micra, were also detected at lower levels.
      The toothbrush bristles impregnated with silver nanoparticles reduced the total
      and individual genome count in the supra- and subgingival biofilm after 4 weeks
      of brushing. Chlorhexidine was not effective in reducing the total genome counts
      in both supra- or subgingival biofilm after 4 weeks of brushing. Chlorhexidine
      reduced the individual genome counts in the supragingival biofilm for most of the
      target species, including putative periodontal pathogens. 

PMID- 25581048
TI  - Targeted therapies in triple-negative breast cancer: failure and future.

PMID- 25581047
TI  - EngageUC: Developing an Efficient and Ethical Approach to Biobanking Research at
      the University of California.
AB  - Biorepositories, or biobanks, provide researchers with access to biological
      samples and associated data in support of translational research. Efficient
      operation and ethical stewardship of biobanks involves coordinated efforts among
      multiple stakeholders including researchers who manage and use the repository,
      institutional officials charged with its oversight, and patients and volunteers
      who contribute samples and data. As advancements in translational research
      increasingly involve more data derived from larger numbers of diverse samples,
      the size and governance challenges facing biorepositories have grown. We describe
      an approach to developing efficient and ethical biobank governance that includes
      all major stakeholders. This model provides a pathway for addressing the
      technical and ethical challenges that must be resolved to ensure biorepositories
      continue to support translational research. 

PMID- 25581049
TI  - Long-term cancer risks in women after treatment with IVF: do we have any answers
      yet?

PMID- 25581050
TI  - Scientific evidence shows the need for a fresh approach to IVF.

PMID- 25581051
TI  - Identifying risks for early onset pre-eclampsia.

PMID- 25581052
TI  - Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for
      the treatment of endometriosis-related pain.
AB  - Suppression of estrogen production and reduction of menstrual blood flow are the
      mainstays of medical treatment of endometriosis-related pain and have been
      traditionally achieved by methods such as combined hormonal contraception,
      progestins and GnRH analogs, all with comparable efficacies, though different
      side-effect profiles. Elagolix is the frontrunner among an emerging class of GnRH
      antagonists, which unlike their peptide predecessors has a nonpeptide structure
      resulting in its oral bioavailability. Phase I and II clinical trials have
      demonstrated safety of elagolix and its efficacy in partial and reversible
      suppression of ovarian estrogen production resulting in improvements in
      endometriosis-related pain. Phase III clinical trials are currently underway and
      elagolix may become a valuable addition to the armamentarium of pharmacological
      agents to treat endometriosis-related pain. 

PMID- 25581053
TI  - Transvaginal ultrasonography and hysteroscopy as predictors of endometrial polyps
      in postmenopause.
AB  - The study compared ultrasound and ambulatorial hysteroscopy as diagnostic methods
      detecting endometrial polyps in postmenopause women. 281 women aged 41-82 years
      who underwent ambulatorial hysteroscopy were analyzed for presence of uterine
      bleeding and/or altered transvaginal ultrasound (endometrial thickness >=5 mm).
      Ultrasonography detected endometrial polyps in 22.8% of patients and endometrial
      thickening in the other 59.8%. Hysteroscopy diagnosed endometrial polyps in
      80.8%. Ultrasonography showed sensitivity of 88.7%, specificity of 25.4%,
      positive predictive value of 81.7%, negative predictive value of 37.5% and
      accuracy of 75.4% in diagnosing endometrial polyps. Hysteroscopy showed 96.4%
      sensitivity, 74.6% specificity, 93.4% positive predictive value, 84.6% negative
      predictive value and 91.8% accuracy. Hysteroscopy demonstrated more accuracy than
      ultrasonography, which is not sufficient for accurate diagnosis. 

PMID- 25581054
TI  - Endometriosis: a role for stem cells.
AB  - Endometriosis is a complex gynecologic condition affecting 6-10% of reproductive
      aged women and is a major cause of chronic pain and infertility. Mechanisms of
      disease pathogenesis are poorly understood. Considerable evidence supports the
      existence of a stem cell population in the endometrium which provides a
      physiologic source of regenerative endometrial cells, and multiple lines of
      evidence now support a key role for stem cells in the pathogenesis of
      endometriosis. In addition, new blood vessel formation is critical for the
      establishment and maintenance of endometriotic implants, a process in which
      endothelial progenitor cells may play an integral role. These new insights into
      disease pathogenesis present exciting opportunities to develop targeted and more
      effective therapeutic options in the management of this common and challenging
      disease. 

PMID- 25581055
TI  - Intimate partner abuse: identifying, caring for and helping women in healthcare
      settings.
AB  - Intimate partner abuse (IPA) is experienced by around one in three women at some
      stage during their lifetime, and has serious health consequences. This paper
      reviews how clinicians can best identify when a woman is experiencing IPA, and
      provide appropriate care and assistance. Research supports use of sensitive
      inquiry about IPA when conditions or situations that can be associated with IPA
      are present. Subsequent responses recommended include validation, affirmation and
      support, safety assessment and planning (both for the woman and any children),
      counseling and referral to IPA specialist services. Better training is needed for
      clinicians in these areas. Future research is needed to compare identification
      methods, and further assess psychological, advocacy and safety planning
      interventions, primary prevention and perpetrator interventions. 

PMID- 25581057
TI  - Female genital cutting: confronting cultural challenges and health complications
      across the lifespan.
AB  - Female genital cutting affects over 140 million women worldwide. Prevalent in
      certain countries of Africa and the Middle East, the practice continues among
      immigrants to industrialized countries. Female genital cutting is a deeply rooted
      tradition that confers honor on a woman and her family, yet also a traumatic
      experience that creates significant dermatological, gynecological, obstetric and
      infectious disease complications. Little is known about postmenopausal health in
      cut women. The international community views this practice as a human rights
      violation. In addition to genital health complications, the medical community
      must confront an understudied concern of what happens as this population ages.
      These challenges must be addressed to provide optimal care to women affected by
      female genital cutting. 

PMID- 25581058
TI  - Multidisciplinary lung cancer meetings: improving the practice of radiation
      oncology and facing future challenges.
AB  - Clinical guidelines widely recognize the importance of multidisciplinary meetings
      (MDM) in the optimal care of lung cancer patients. The published literature
      suggest that dedicated Lung Cancer MDM lead to increased treatment utilization
      rates and improved survival outcomes for patients with lung cancer. For radiation
      oncologists, Lung Cancer MDM have been proven to support evidence-based practice
      and improve the utilization of radiotherapy. Lung Cancer MDM also allow for
      education and promotion of specialty radiotherapy services. The fast pace of
      modern medicine is also presenting new challenges for the multidisciplinary lung
      cancer team, and technological advances are likely to lead to new changes in the
      structure of traditional Lung Cancer MDM. 

PMID- 25581059
TI  - Evaluation of immunological interaction between spermatozoa and fallopian tube
      epithelial cells.
AB  - Toll-like receptors (TLR) are one of the major compartments of innate immune
      system. It was revealed that the TLR have relevance in ovulation, sperm
      capacitation and fertilisation. So, in this study, the expression of TLR, their
      adaptor molecules and cytokines in human fallopian tube cell line under the
      effect of human normal spermatozoa was evaluated. TLR mRNA and protein were
      evaluated in OE-E6/E7 cell line. Semen samples from 10 donors were collected and
      co-incubated with OE-E6/E7 cell line and used as sperm group, and cell line
      without spermatozoa was used as control group. Afterwards, the level of TLR,
      their adaptor molecule and cytokine mRNA expression was compared using qPCR in
      sperm and control groups, and supernatant was used for ELISA. To determine
      whether elevated cytokine reaction to spermatozoa in OE-E6/E7 cell line is
      mediated via TLR, TLR3 function-blocking antibody was used. OE-E6/E7 cell line
      expressed TLR1-6 genes and proteins. TLR expressions, especially TLR3 and TLR5,
      in OE-E6/E7 cell line under the effect of spermatozoa were significantly higher.
      Also, levels of adaptor molecules and cytokine production were increased in sperm
      group than in control group (P < 0.05). So, it may be hypothesised that TLR are
      essential for spermatozoa and fallopian tube immunological interaction and for
      preparing safe environment for important events in fallopian tube.

PMID- 25581060
TI  - Systemically administered neuregulin-1beta1 rescues nigral dopaminergic neurons
      via the ErbB4 receptor tyrosine kinase in MPTP mouse models of Parkinson's
      disease.
AB  - Previously, we demonstrated that systemically injected extracellular domain of
      neuregulin-1beta1 (Nrg1beta1), a nerve growth and differentiation factor, passes
      the blood-brain barrier and rescues dopaminergic neurons of substantia nigra in
      the 6-hydroxydopamine-mouse model of Parkinson's disease (PD). Here, we studied
      the effects of peripherally administered Nrg1beta1 in another toxin-based mouse
      model of PD. For this purpose, (i) nigrostriatal pathway injury was induced by
      treatment of adult wild-type mice with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) in acute and subchronic paradigms; and (ii) Nrg1beta1
      or saline (control) were administered 1 h before each MPTP injection. We found
      that Nrg1beta1 significantly reduced the loss of nigral dopaminergic neurons in
      both intoxication paradigms (7 days post-injection). However, Nrg1beta1 did not
      reverse MPTP-induced decrease in dopamine levels and dopaminergic fibers in the
      striatum. We also show that MPTP conversion to its toxic metabolite 1-methyl-4
      phenylpyridinium as well as levels of dopamine transporter, mediating
      intracellular uptake of 1-methyl-4-phenylpyridinium, are unaffected by Nrg1beta1.
      Finally, neuroprotective properties of Nrg1beta1 on nigral dopaminergic neurons
      are specifically mediated by ErbB4 as revealed through the study of ErbB4
      knockout mice. In conclusion, systemically administered Nrg1beta1 protects
      midbrain dopaminergic neurons against this PD-related toxic insult. Thus,
      Nrg1beta1 may have a benefit in the treatment of PD patients. Previously, we
      demonstrated that systemically administered neuregulin-1beta1 (Nrg1beta1) passes
      the blood-brain barrier, phosphorylates ErbB4 receptors and elevates dopamine
      (DA) levels in the nigrostriatal system of healthy mice. Nrg1beta1 protects
      nigral DAergic neurons in the 6-hydroxydopamine (6-OHDA) mouse model of
      Parkinson's disease (PD). Here, we show that Nrg1beta1 rescues nigral DAergic
      neurons also against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
      cell death. ErbB4 expression is essential for the neuroprotective effect of
      Nrg1beta1 on midbrain DAergic neurons. Nrg1beta1 might be beneficial in PD
      treatment.

PMID- 25581056
TI  - Links between alcohol consumption and breast cancer: a look at the evidence.
AB  - Alcohol consumption by adult women is consistently associated with risk of breast
      cancer. Several questions regarding alcohol and breast cancer need to be
      addressed. Menarche to first pregnancy represents a window of time when breast
      tissue is particularly susceptible to carcinogens. Youth alcohol consumption is
      common in the USA, largely in the form of binge drinking and heavy drinking.
      Whether alcohol intake acts early in the process of breast tumorigenesis is
      unclear. This review aims to focus on the influences of timing and patterns of
      alcohol consumption and the effect of alcohol on intermediate risk markers. We
      also review possible mechanisms underlying the alcohol-breast cancer association.

PMID- 25581062
TI  - Income Transfers and Maternal Health: Evidence from a National Randomized Social
      Cash Transfer Program in Zambia.
AB  - There is promising recent evidence that poverty-targeted social cash transfers
      have potential to improve maternal health outcomes; however, questions remain
      surrounding design features responsible for impacts. In addition, virtually no
      evidence exists from the African region. This study explores the impact of
      Zambia's Child Grant Program on a range of maternal health utilization outcomes
      using a randomized design and difference-in-differences multivariate regression
      from data collected over 24 months from 2010 to 2012. Results indicate that while
      there are no measurable program impacts among the main sample, there are
      heterogeneous impacts on skilled attendance at birth among a sample of women
      residing in households having better access to maternal health services. The
      latter result is particularly interesting because of the overall low level of
      health care availability in program areas suggesting that dedicated program
      design or matching supply-side interventions may be necessary to leverage
      unconditional cash transfers in similar settings to impact maternal health.

PMID- 25581061
TI  - Global variability in leaf respiration in relation to climate, plant functional
      types and leaf traits.
AB  - Leaf dark respiration (Rdark ) is an important yet poorly quantified component of
      the global carbon cycle. Given this, we analyzed a new global database of Rdark
      and associated leaf traits. Data for 899 species were compiled from 100 sites
      (from the Arctic to the tropics). Several woody and nonwoody plant functional
      types (PFTs) were represented. Mixed-effects models were used to disentangle
      sources of variation in Rdark . Area-based Rdark at the prevailing average daily
      growth temperature (T) of each site increased only twofold from the Arctic to the
      tropics, despite a 20 degrees C increase in growing T (8-28 degrees C). By
      contrast, Rdark at a standard T (25 degrees C, Rdark (25) ) was threefold higher
      in the Arctic than in the tropics, and twofold higher at arid than at mesic
      sites. Species and PFTs at cold sites exhibited higher Rdark (25) at a given
      photosynthetic capacity (Vcmax (25) ) or leaf nitrogen concentration ([N]) than
      species at warmer sites. Rdark (25) values at any given Vcmax (25) or [N] were
      higher in herbs than in woody plants. The results highlight variation in Rdark
      among species and across global gradients in T and aridity. In addition to their
      ecological significance, the results provide a framework for improving
      representation of Rdark in terrestrial biosphere models (TBMs) and associated
      land-surface components of Earth system models (ESMs). 

PMID- 25581063
TI  - Pharmacokinetic interactions among imatinib, bosentan and sildenafil, and their
      clinical implications in severe pulmonary arterial hypertension.
AB  - AIMS: This study characterized the population pharmacokinetics (PK) of imatinib
      in patients with severe pulmonary arterial hypertension (PAH), investigated drug
      drug interactions (DDI) among imatinib, sildenafil and bosentan, and evaluated
      their clinical implications. METHODS: Plasma concentrations of imatinib, bosentan
      and sildenafil were collected in a phase III study and were used to characterize
      the PK of imatinib in this population. DDIs among the three drugs were quantified
      using a linear mixed model and log-transformed drug concentrations. RESULTS: The
      population mean estimates of apparent clearance (CL/F) and volume (V/F) were 10.8
      l h(-1) (95% CI 9.2, 12.4 l h(-1) ) and 267 l (95% CI 208, 326 l), respectively.
      It was estimated that sildenafil concentrations increased, on average, by 64%
      (95% CI 32%, 103%) and bosentan concentrations by 51% (95% CI 12%, 104%), in the
      presence of imatinib. Despite increased concentrations of co-medications,
      treatment differences between imatinib and placebo for change in 6 min walk
      distance and pulmonary vascular resistance were relatively constant across the
      entire concentration range for sildenafil and bosentan. Overall, higher
      concentrations of imatinib and bosentan were not associated with increasing liver
      enzymes (serum glutamic oxaloacetic transaminases [SGOT]/serum glutamic-pyruvic
      transaminase [SGPT]). CONCLUSIONS: Population PKs of imatinib in patients with
      severe PAH were found comparable with those of patients with chronic myeloid
      leukemia. Imatinib was found effective regardless of the co-medications and
      showed intrinsic efficacy beyond merely elevating the concentrations of the co
      medications due to DDIs. There was no evidence of increased risk of liver
      toxicity upon co-administration with bosentan.

PMID- 25581064
TI  - Structural and functional analysis of the loading acyltransferase from avermectin
      modular polyketide synthase.
AB  - The loading acyltransferase (AT) domains of modular polyketide synthases (PKSs)
      control the choice of starter units incorporated into polyketides and are
      therefore attractive targets for the engineering of modular PKSs. Here, we report
      the structural and biochemical characterizations of the loading AT from
      avermectin modular PKS, which accepts more than 40 carboxylic acids as
      alternative starter units for the biosynthesis of a series of congeners. This
      first structural analysis of loading ATs from modular PKSs revealed the molecular
      basis for the relaxed substrate specificity. Residues important for substrate
      binding and discrimination were predicted by modeling a substrate into the active
      site. A mutant with altered specificity toward a panel of synthetic substrate
      mimics was generated by site-directed mutagenesis of the active site residues.
      The hydrolysis of the N-acetylcysteamine thioesters of racemic 2-methylbutyric
      acid confirmed the stereospecificity of the avermectin loading AT for an S
      configuration at the C-2 position of the substrate. Together, these results set
      the stage for region-specific modification of polyketides through active site
      engineering of loading AT domains of modular PKSs. 

PMID- 25581065
TI  - Health care professionals' experience-based understanding of individuals'
      capacity to work while depressed and anxious.
AB  - AIM: The meaning of capacity to work while depressed and anxious is not well
      comprehended. The aim of this study was to explore and describe health care
      professionals' experience-based understanding of capacity to work in individuals
      with depression and/or anxiety disorders. METHOD: An exploratory qualitative
      design was used. Four focus groups were conducted with 21 professionals from
      psychiatric, occupational, and primary health care. Data were analysed using
      inductive content analysis. RESULTS: Capacity to work while depressed and anxious
      was understood as a change from the familiar to a no longer recognizable
      performance at work. Managing time, daily work demands, and emotions was
      described as difficult for the patients, and capacity to work could be fragmented
      by anxiety attacks. Patients were perceived as continuing to work while life
      outside work crumbled. Capacity to work was described as part of a greater whole,
      the work community, and the patient's participation in the work community was
      considered problematic. CONCLUSIONS: The findings provide a deeper understanding
      of the reduced capacity to work compared with theoretical or medico
      administrative descriptions. Applied to patient encounters it could promote
      fitness-for-work dialogues, rehabilitation, and tailor-made work interventions.

PMID- 25581066
TI  - Autophagy is involved in the reduction of myelinating Schwann cell cytoplasm
      during myelin maturation of the peripheral nerve.
AB  - Peripheral nerve myelination involves dynamic changes in Schwann cell morphology
      and membrane structure. Recent studies have demonstrated that autophagy regulates
      organelle biogenesis and plasma membrane dynamics. In the present study, we
      investigated the role of autophagy in the development and differentiation of
      myelinating Schwann cells during sciatic nerve myelination. Electron microscopy
      and biochemical assays have shown that Schwann cells remove excess cytoplasmic
      organelles during myelination through macroautophagy. Inhibition of autophagy via
      Schwann cell-specific removal of ATG7, an essential molecule for macroautophagy,
      using a conditional knockout strategy, resulted in abnormally enlarged abaxonal
      cytoplasm in myelinating Schwann cells that contained a large number of ribosomes
      and an atypically expanded endoplasmic reticulum. Small fiber hypermyelination
      and minor anomalous peripheral nerve functions are observed in this mutant.
      Rapamycin-induced suppression of mTOR activity during the early postnatal period
      enhanced not only autophagy but also developmental reduction of myelinating
      Schwann cells cytoplasm in vivo. Together, our findings suggest that autophagy is
      a regulatory mechanism of Schwann cells structural plasticity during myelination.

PMID- 25581067
TI  - Cross-cultural evidence of value structures and priorities in childhood.
AB  - We broaden the developmental focus of the theory of universals in basic human
      values (Schwartz, 1992, Advances in Experimental Social Psychology) by presenting
      supportive evidence on children's values from six countries: Germany, Italy,
      Poland, Bulgaria, the United States, and New Zealand. 3,088 7-11-year-old
      children completed the Picture-Based Value Survey for Children (PBVS-C, Doring et
      al., 2010, J. Pers. Assess., 92, 439). Grade 5 children also completed the
      Portrait Values Questionnaire (PVQ, Schwartz, 2003, A proposal for measuring
      value orientations across nations. Chapter 7 in the Questionnaire Development
      Package of the European Social Survey). Findings reveal that the broad value
      structures, sex differences in value priorities and pan-cultural value
      hierarchies typical of adults have already taken form at this early age. We
      discuss the conceptual implications of these findings for the new field of
      children's basic values by embedding them in the recent developmental literature.

PMID- 25581068
TI  - Drug-induced liver injury in a chronic hepatitis C patient treated by
      peginterferon, ribavirin and simeprevir.
AB  - A 56-year-old male patient with chronic hepatitis C was treated with pegylated
      interferon (PEG IFN)-alpha-2b and ribavirin (RBV) for 72 weeks in 2006. The
      patient achieved an early virological response (EVR); however, hepatitis C
      relapsed 12 weeks after discontinuation of PEG IFN and RBV. In 2012, the patient
      was treated with a PEG IFN/RBV/telaprevir combination therapy. After 5 days of
      treatment, he suffered from a telaprevir-associated skin rash on his body and
      four limbs. He chose to be treated with PEG IFN and RBV until 60 weeks. He again
      achieved EVR but no sustained virological response. In 2014, he was treated with
      PEG IFN/RBV/simeprevir combination therapy. He achieved rapid virological
      response, but after 6 weeks of therapy, a striking elevation of serum
      aminotransferase level was recorded with no accompanying skin rash; he was
      admitted to our hospital. PEG IFN/RBV/simeprevir was stopped, but sodium
      valproate (400 mg/day), which had been administrated for more than 10 years to
      prevent epilepsy was continued. Liver biopsy revealed typical features of drug
      induced liver injury. After stopping PEG IFN/RBV/simeprevir, serum
      aminotransferase levels soon returned to the normal range. We diagnosed this case
      to be simeprevir-induced hepatitis clinically and histologically. Physicians need
      to stay alert to the possibility of drug-induced liver injury in using
      simeprevir. 

PMID- 25581069
TI  - Immediate and extended effects of abrasion on stratum corneum natural
      moisturizing factor.
AB  - BACKGROUND: Natural moisturizing factor (NMF), principally comprised of
      hygroscopic amino acids and derivatives that absorb moisture from the surrounding
      environment, serves as the primary humectant of the stratum corneum (SC). Acute
      barrier disruption has been shown to differentially affect the concentration of
      NMF in the SC. This study measured the recovery kinetics of NMF after mechanical
      damage of the SC, which is not well understood. METHODS: The study population
      included 20 healthy female volunteers (18-72-year old) with no history of
      dermatological disorders. Transepidermal water loss (TEWL), erythema, and SC
      water and NMF were measured at all sites before abrasion, 30 min following
      abrasion, and 1-3, 6, 8, and 10 days following abrasion. Measurements obtained
      from the abraded site were compared with those obtained from an untreated site.
      RESULTS: As expected, both TEWL and erythema increased significantly with
      abrasion. Erythema and TEWL values remained higher at the abraded site for 2 and
      6 days, respectively, after abrasion. No changes in NMF component levels in the
      SC were observed at 30 min after abrasion. One day following abrasion, reduced
      levels of glycine, histidine pH4, trans-urocanic acid (tUca) pH4, and tUca pH8
      were observed. In addition, a significantly lower level of serine was observed at
      the abraded site 2 and 6 days following abrasion. Within 8 days after abrasion,
      these components returned to levels comparable to those observed in untreated
      skin. Throughout the study, no differences were observed in the level of water in
      the SC. CONCLUSION: These results demonstrate that acute barrier disruption
      induced by mechanical abrasion has relatively little impact on biochemical events
      responsible for NMF generation. Though reductions in certain NMF components were
      observed, abrasion had no measureable effect on SC water content over the
      duration of the study. This implies that the reduced NMF components may not
      contribute substantially to water retention in the SC. The reduced components
      belong to a group of NMF molecules thought to be principally derived through
      degradation of S-100 proteins in the epidermis. NMF components measured in this
      study that are derived from sweat and/or urea cycling were not impacted. These
      data imply that while abrasion elicits clinical signs of barrier disruption
      within the SC, effects on its biochemical constituents and ability to retain
      water are relatively minor.

PMID- 25581070
TI  - Rapid declines of large mammal populations after the collapse of the Soviet
      Union.
AB  - Anecdotal evidence suggests that socioeconomic shocks strongly affect wildlife
      populations, but quantitative evidence is sparse. The collapse of socialism in
      Russia in 1991 caused a major socioeconomic shock, including a sharp increase in
      poverty. We analyzed population trends of 8 large mammals in Russia from 1981 to
      2010 (i.e., before and after the collapse). We hypothesized that the collapse
      would first cause population declines, primarily due to overexploitation, and
      then population increases due to adaptation of wildlife to new environments
      following the collapse. The long-term Database of the Russian Federal Agency of
      Game Mammal Monitoring, consisting of up to 50,000 transects that are monitored
      annually, provided an exceptional data set for investigating these population
      trends. Three species showed strong declines in population growth rates in the
      decade following the collapse, while grey wolf (Canis lupus) increased by more
      than 150%. After 2000 some trends reversed. For example, roe deer (Capreolus
      spp.) abundance in 2010 was the highest of any period in our study. Likely
      reasons for the population declines in the 1990s include poaching and the erosion
      of wildlife protection enforcement. The rapid increase of the grey wolf
      populations is likely due to the cessation of governmental population control. In
      general, the widespread declines in wildlife populations after the collapse of
      the Soviet Union highlight the magnitude of the effects that socioeconomic shocks
      can have on wildlife populations and the possible need for special conservation
      efforts during such times.

PMID- 25581071
TI  - Energy decomposition analysis of cation-pi, metal ion-lone pair, hydrogen bonded,
      charge-assisted hydrogen bonded, and pi-pi interactions.
AB  - This study probes the nature of noncovalent interactions, such as cation-pi,
      metal ion-lone pair (M-LP), hydrogen bonding (HB), charge-assisted hydrogen
      bonding (CAHB), and pi-pi interactions, using energy decomposition schemes
      density functional theory (DFT)-symmetry-adapted perturbation theory and reduced
      variational space. Among cation-pi complexes, the polarization and electrostatic
      components are the major contributors to the interaction energy (IE) for metal
      ion-pi complexes, while for onium ion-pi complexes (NH4+, PH4+, OH3+, and SH3+)
      the dispersion component is prominent. For M-LP complexes, the electrostatic
      component contributes more to the IE except the dicationic metal ion complexes
      with H2 S and PH3 where the polarization component dominates. Although
      electrostatic component dominates for the HB and CAHB complexes, dispersion is
      predominant in pi-pi complexes.

PMID- 25581072
TI  - Effect of low viscous nondipolar solvent on the rotational diffusion of
      structurally similar nondipolar solutes in an ionic liquid.
AB  - Fluorescence anisotropies of two structurally similar nondipolar solutes, 2,5
      dimethyl-1,4-dioxo-3,6-diphenylpyrrolo[3,4-c]pyrrole (DMDPP) and 1,4-dioxo-3,6
      diphenylpyrrolo[3,4-c]pyrrole (DPP), have been measured in 1-methyl-3
      octylimidazolium hexafluorophosphate-dibenzyl ether ([MOIM][PF6]-DBE) mixtures to
      understand how the addition of a low viscous nondipolar solvent influences solute
      rotation. The data when analyzed with Stokes-Einstein-Debye hydrodynamic theory
      reveals that the measured reorientation times of DMDPP are closer to the
      predictions of slip boundary condition, whereas those of DPP follow stick
      hydrodynamics. This outcome arises due to specific interactions between DPP and
      the solvent medium. Nevertheless, the important result of this study is that the
      rotational diffusion of DMDPP becomes gradually slower with an increase in the
      mole fraction of DBE (xDBE) for a given viscosity and temperature. In contrast,
      such a trend is not noticed for the hydrogen-bond donating solute DPP. Instead,
      two sets of reorientation times have been obtained, one corresponding to xDBE =
      0.0-0.2 and the other xDBE = 0.4-1.0. The results for DMDPP have been
      rationalized on the basis of the organized structure of [MOIM][PF6], which
      attains homogeneity at the microscopic level with an increase in xDBE. In case of
      DPP, however, the propensity of the solute to be in the neighborhood of DBE, as a
      consequence of its stronger hydrogen bond accepting ability compared to the ionic
      liquid, appears to be the reason for the observed behavior. 

PMID- 25581075
TI  - Editorial.
AB  - This editorial introduces the Journal of Applied Psychology. More specifically
      the editor wants to share with you (a) the journal's scope and mission, (b)
      expectations for different types of articles considered by the journal, and (c)
      the review process used. The information included is also based on the editorial
      team's consideration of current trends in the psychological and organizational
      sciences, as well as emerging changes in peer review processes within the social
      sciences. (PsycINFO Database Record (c) 2015 APA, all rights reserved). 

PMID- 25581074
TI  - Cost-effectiveness analysis of two rituximab retreatment regimens for
      longstanding rheumatoid arthritis.
AB  - OBJECTIVE: Rituximab (RTX) is licensed for second-line treatment of rheumatoid
      arthritis (RA) after first tumor necrosis factor (TNF) inhibitor failure. RTX is
      generally administered intravenously at 1 gm 2 weeks apart, and the retreatment
      is scheduled at the time of clinical relapse (regimen 1). A more intensive
      regimen is proposed with a fixed full cycle after 6 months (regimen 2) if
      remission is not reached. A cost-effectiveness analysis (CEA) compared these 2
      regimens of RTX administration in patients with longstanding RA based on data
      provided by an observational study. METHODS: An observational retrospective study
      was conducted on 102 patients, enrolled in 3 hospitals and followed for >=12
      months. Forty-seven patients followed regimen 1, while 55 patients followed
      regimen 2. A CEA based on a Markov model was conducted. A lifelong and social
      perspective was adopted. CEA was conducted for the entire cohort and for the 2
      subgroups separately (patients with positive rheumatoid factor and/or anti-cyclic
      citrullinated peptide and failures to TNF inhibitors). RESULTS: Results for the
      overall sample show at 10, 20, and 30 years that regimen 1 is less costly and
      associated with a higher quality of life compared to regimen 2. Probabilistic
      sensitivity analysis at 10 years estimated a probability of 95.1% for regimen 1
      to be cost effective given a willingness to pay of ?35,000/quality-adjusted life
      year, while for seropositive patients and for TNF failures it was estimated to be
      92% and 92.7%, respectively. CONCLUSION: In longstanding RA, cost effectiveness
      of RTX retreatment at clinical relapse was found to be at least equivalent to the
      more intensive regimen proposed.

PMID- 25581073
TI  - Intraoperative simulation of remnant liver function during anatomic liver
      resection with indocyanine green clearance (LiMON) measurements.
AB  - OBJECTIVE: Post-hepatectomy liver failure (PHLF) is the major cause of death
      following liver resection. The aim of this study was to evaluate the feasibility
      of an intraoperative simulation of post-resection liver function. METHODS:
      Intraoperative liver function was measured by indocyanine green (ICG) clearance
      using the LiMON technology. In 20 patients undergoing anatomic liver resection,
      ICG plasma disappearance rate (PDR (%/min) and ICG retention at 15 min (R15 ) (%)
      were measured immediately after the induction of anaesthesia (t0 ), after
      selective arterial and portovenous inflow trial clamping (TC) of the resected
      liver segments (t1 ), after the completion of resection (t2 ) and before the
      closure of the abdominal cavity (t3 ). RESULTS: The median baseline (t0 ) PDR was
      16.5%/min. Trial clamping of the inflow (t1 ) resulted in a significant reduction
      in PDR to 10.5%/min. Results under TC were similar to those obtained after
      resection (t2 ) (median PDR: 10.5%/min). Linear regression modelling showed that
      post-resection liver volume could be accurately predicted by TC of liver inflow
      (P < 0.0001), but not by determining the resected liver volume. Simulated post
      resection liver function under TC correlated well with PHLF and length of
      hospital stay. CONCLUSIONS: Intraoperative ICG clearance measurements allow real
      time monitoring of intraoperative liver function during surgery. Trial clamping
      of arterial and portovenous inflow accurately predicts immediate post-resection
      liver function. The intraoperative measurement of liver function and simulation
      of post-resection liver function may help to avoid PHLF.

PMID- 25581076
TI  - Tigecycline exerts an antitumoral effect in oral squamous cell carcinoma.
AB  - OBJECTIVE: To explore whether antibacterial drug tigecycline could exert an
      antitumoral effect in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS:
      Two OSCC cell lines Tca8113 and KB were used in this study. To investigate the
      cytostatic effects of tigecycline in OSCC, cell growth was tested by trypan blue
      staining, MTT assay, and Brdu immunofluorescence staining. Then, the apoptosis
      proportion was measured by FITC Annexin-V and PI labeling, and cell cycle was
      determined by PI staining. The expression of caspase 3 (CASP3) and cell cycle
      regulatory protein was detected by Western blot assay. Finally, the clonogenesis
      and tumorigenesis capacity were analyzed by soft agar growth and xenograft model.
      RESULTS: Here, we showed that tigecycline significantly inhibited cell growth and
      proliferation in OSCC cell lines Tca8113 and KB. It did not induce cell apoptosis
      but led to an increase of cells in G0/G1 phase with down-regulation of cyclin E2
      (CCNE2) and cyclin-dependent kinase4 (CDK4) protein expression. We also showed
      that tigecycline inhibited colony formation in soft agar and reduced tumor growth
      in a xenograft model. CONCLUSION: Our results suggested that tigecycline might be
      used as a novel candidate agent for the treatment of OSCC.

PMID- 25581079
TI  - End-of-life care in the intensive care unit: how Asia differs from the West.

PMID- 25581078
TI  - A retrospective longitudinal study of cognitive and language skills in poor
      reading comprehension.
AB  - Fifty-six specific poor reading comprehenders (SPRC) were selected in Grade 4 and
      retrospectively compared to good comprehenders at preschool (age 5) and at the
      end of kindergarten, Grade 1, and Grade 2. The results revealed deficits in
      vocabulary, grammar, verbal memory and early deficits in phonological awareness
      in most of the SPRC sample, beginning in preschool. The reading comprehension
      deficits in children with SPRC were not as marked in earlier assessments in Grade
      1 and 2, probably because of the greater dependence on word decoding in reading
      comprehension in the early grades. 

PMID- 25581080
TI  - Transvaginal anal sphincter repair--a video vignette.

PMID- 25581077
TI  - Competition with and without priority control: linking rivalry to attention
      through winner-take-all networks with memory.
AB  - Competition is ubiquitous in perception. For example, items in the visual field
      compete for processing resources, and attention controls their priority (biased
      competition). The inevitable ambiguity in the interpretation of sensory signals
      yields another form of competition: distinct perceptual interpretations compete
      for access to awareness. Rivalry, where two equally likely percepts compete for
      dominance, explicates the latter form of competition. Building upon the
      similarity between attention and rivalry, we propose to model rivalry by a
      generic competitive circuit that is widely used in the attention literature-a
      winner-take-all (WTA) network. Specifically, we show that a network of two
      coupled WTA circuits replicates three common hallmarks of rivalry: the
      distribution of dominance durations, their dependence on input strength
      ("Levelt's propositions"), and the effects of stimulus removal (blanking). This
      model introduces a form of memory by forming discrete states and explains
      experimental data better than competitive models of rivalry without memory. This
      result supports the crucial role of memory in rivalry specifically and in
      competitive processes in general. Our approach unifies the seemingly distinct
      phenomena of rivalry, memory, and attention in a single model with competition as
      the common underlying principle. 

PMID- 25581081
TI  - Vulvodynia--An Evidence-Based Literature Review and Proposed Treatment Algorithm.
AB  - OBJECTIVE: We searched the medical literature from the last 15 years (1998 to
      2013) relating to the etiology, diagnosis, and treatment of vulvodynia. The
      evidence was reviewed supporting the therapeutic proposals currently in use and
      propose the incorporation of novel, minimally invasive, interventional therapies,
      within the context of a multidisciplinary approach. METHODS: This was a
      systematic review of all relevant studies with no language restrictions. Studies
      were identified through Medline/PubMed (1998 to March 2013), the Cochrane Library
      (2001 to 2013), and conference records and book chapters. The keywords used
      included "chronic pelvic pain," "vulvodynia," "vestibulodynia," and search terms
      "etiology," "diagnosis," and "treatment" were added. The levels of evidence were
      assessed using grading system for "Therapy/Prevention/Etiology/Harm" developed by
      the Centre for Evidence-Based Medicine (CEBM). The grading system assists in
      clinical decision-making, and we decided to use "The Grading of Recommendations
      Assessment, Development, and Evaluation (GRADE)." RESULTS: A total of 391 papers
      were assessed. Of these, 215 were analyzed and 175 were excluded, as they
      pertained to areas not directly related to the disease under review. CONCLUSION:
      The optimal therapy for vulvar pain syndrome remains elusive, with low
      percentages of therapeutic success, using either local or systemic
      pharmacological approaches. Surgery involving invasive and often irreversible
      therapeutic procedures has resulted in success for certain subtypes of
      vulvodynia. We present a multidisciplinary approach whereby pain treatment units
      may provide an intermediate level of care between standard medical and surgical
      treatments.

PMID- 25581082
TI  - Concerns of ABO incompatible and crossmatch-positive potential donors and
      recipients about participating in kidney exchanges.
AB  - Kidney paired exchanges (KPEs) have increased, yet are still underutilized. This
      study aimed to develop tools for assessing KPE concerns, identify predictors of
      KPE concerns, and describe common KPE concerns among potential living donors
      (LDs) and intended recipients. Incompatible former potential LDs (n = 135) and
      intended recipients (n = 83) retrospectively completed questionnaires to assess
      KPE concerns. Healthcare system distrust also was assessed. A minority (n = 48 or
      36.5% of potential LDs; n = 25 or 30.1% of intended recipients) had pursued KPE
      participation. Of those who pursued KPE participation, 11 (22.9%) and 6 (24.0%)
      completed KPE donation or transplantation, respectively. The questionnaires for
      potential LDs and recipients showed good internal consistency and preliminary
      convergent validity. LDs and patients less willing to pursue KPE reported more
      KPE concerns. Common KPE concerns for both potential LDs and recipients were
      related to perceived Distrust/Inequity and Inconvenience/Cost. Multivariate
      predictors of more KPE concerns were as follows: male gender (t = 4.5, p < 0.001)
      and more healthcare system distrust (t = 2.5, p = 0.01) for potential LDs; black
      race (t = 2.1, p = 0.04) and more healthcare system distrust (t = 2.3, p = 0.03)
      for intended recipients. These findings underscore the importance of addressing
      concerns potential LDs and patients have about KPE if the true potential of KPE
      is to be realized.

PMID- 25581083
TI  - Immobilization of Ag(i) into a metal-organic framework with -SO3H sites for
      highly selective olefin-paraffin separation at room temperature.
AB  - Introduction of Ag(i) ions into a sulfonic acid functionalized MOF ((Cr)-MIL-101
      SO3H) significantly enhances its interactions with olefin double bonds, leading
      to its much higher selectivities for the separation of C2H4-C2H6 and C3H6-C3H8 at
      room temperature over the original (Cr)-MIL-101-SO3H and other adsorbents at room
      temperature. 

PMID- 25581084
TI  - Metabolic syndrome in patients with coeliac disease on a gluten-free diet.
AB  - BACKGROUND: Several studies have shown that weight changes are common in patients
      with coeliac disease after starting a gluten-free diet (GFD), but data on the
      prevalence of metabolic syndrome in this population are still scarce. AIMS: To
      assess the prevalence of metabolic syndrome in patients with CD at diagnosis and
      1 year after starting GFD. METHODS: We enrolled all consecutive patients with
      newly diagnosed coeliac disease (CD) who were referred to our third-level CD
      Unit. For all patients we collected: waist circumference, BMI, blood pressure,
      lipid profile (HDL cholesterol, triglycerides) and levels of blood glucose.
      Diagnosis of metabolic syndrome was made according to the International Diabetes
      Federation (IDF) criteria for European countries. The prevalence of metabolic
      syndrome was re-assessed after 12 months of GFD. RESULTS: Ninety-eight patients
      with CD were assessed, two patients with CD (2%) fulfilled the diagnostic
      criteria for metabolic syndrome at diagnosis and 29 patients (29.5%) after 12
      months of GFD (P < 0.01; OR: 20). With regard to metabolic syndrome sub
      categories 1 year after GFD compared to baseline respectively: 72 vs. 48 patients
      exceeded waist circumference cut-off (P < 0.01; OR: 2.8); 18 vs. 4 patients had
      high blood pressure (P < 0.01; OR: 5.2); 25 vs. 7 patients exceeded glycemic
      threshold (P = 0.01; OR: 4.4); 34 vs. 32 patients with CD had reduced levels of
      HDL cholesterol (P = 0.7); and 16 vs. 7 patients had high levels of triglycerides
      (P = 0.05). CONCLUSIONS: Patients with coeliac disease show a high risk of
      metabolic syndrome 1 year after starting a gluten-free diet. We suggest that an
      in-depth nutritional assessment is undertaken for all patients with coeliac
      disease.

PMID- 25581085
TI  - Depressive disorder in pregnant Latin women: does intimate partner violence
      matter?
AB  - AIMS AND OBJECTIVES: To identify the association of antenatal depressive symptoms
      with intimate partner violence during the current pregnancy in Brazilian women.
      BACKGROUND: Intimate partner violence is an important risk factor for antenatal
      depression. To the authors' knowledge, there has been no study to date that
      assessed the association between intimate partner violence during pregnancy and
      antenatal depressive symptoms among Brazilian women. DESIGN: Cross-sectional
      study. METHODS: Three hundred and fifty-eight pregnant women were enrolled in the
      study. The Edinburgh Postnatal Depression Scale and an adapted version of the
      instrument used in the World Health Organization Multi-country Study on Women's
      Health and Domestic Violence were used to measure antenatal depressive symptoms
      and psychological, physical and sexual acts of intimate partner violence during
      the current pregnancy respectively. Multiple logistic regression and multiple
      linear regression were used for data analysis. RESULTS: The prevalence of
      antenatal depressive symptoms, as determined by the cut-off score of 12 in the
      Edinburgh Postnatal Depression Scale, was 28.2% (101). Of the participants, 63
      (17.6%) reported some type of intimate partner violence during pregnancy. Among
      them, 60 (95.2%) reported suffering psychological violence, 23 (36.5%) physical
      violence and one (1.6%) sexual violence. Multiple logistic regression and
      multiple linear regression indicated that antenatal depressive symptoms are
      extremely associated with intimate partner violence during pregnancy. CONCLUSION:
      Among Brazilian women, exposure to intimate partner violence during pregnancy
      increases the chances of experiencing antenatal depressive symptoms. RELEVANCE TO
      CLINICAL PRACTICE: Clinical nurses and nurses midwifes should pay attention to
      the particularities of Brazilian women, especially with regard to the occurrence
      of intimate partner violence, whose impacts on the mental health of this
      population are extremely significant, both during the gestational period and
      postpartum.

PMID- 25581087
TI  - The impact of disrupted childhood attachment on the presentation of psychogenic
      erectile dysfunction: an exploratory study.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a common form of male sexual
      dysfunction. Psychological factors play an important role in the onset and
      persistence of ED. Disturbed childhood attachment is a biologically and
      psychologically plausible predisposing factor for psychogenic ED that has not
      been systematically studied to date. AIM: This study aims to assess the frequency
      and correlates of events associated with parental separation (actual or
      threatened) and loss in men with a diagnosis of psychogenic ED. METHODS: The case
      records of 46 men who presented to a clinic for psychosexual disorders in the
      period 2012-2013, and were diagnosed with psychogenic ED using a semi-structured
      interview schedule, were reviewed. RESULTS: Events causing actual or potential
      disturbed attachment (DA) in childhood were reported by 20 of 46 men with
      psychogenic ED (43.5%). This group of men (DA+) had an earlier age at onset of ED
      (median 25 vs. 29 years, P = 0.005), were more likely to be single (15/20 vs.
      5/26 (chi(2)  = 14.307, P < 0.001), reported sexual performance anxiety more
      frequently (12/20 vs. 7/26, chi(2)  = 5.101, P = 0.024), and were more likely to
      develop ED in the absence of a proximate stressor (4/20 vs. 15/26, P = 0.015).
      They also showed a trend toward being more likely to report guilt over early
      sexual experiences as a contributory factor (5/20 vs. 1/26, P = 0.072). In a
      binary logistic regression analysis, the presence of performance anxiety (B =
      2.01, P = 0.023) and marital status (B = -2.85, P = 0.001) were significantly
      associated with events causing DA. CONCLUSIONS: Disrupted childhood attachment
      was common in our sample of men with ED and is associated with significant
      differences in their clinical profile, particularly an earlier onset, a lower
      likelihood of being married, and higher rates of performance anxiety. This study
      highlights the need to consider early childhood experiences, particularly using
      an attachment theory framework, when examining the origins of psychogenic
      erectile dysfunction.

PMID- 25581086
TI  - Maternal Depression, Parenting, and Youth Depressive Symptoms: Mediation and
      Moderation in a Short-Term Longitudinal Study.
AB  - Although multiple studies find that offspring of depressed mothers are at risk
      for depressive disorders, there is uncertainty about the specific mechanisms that
      are at work--particularly with respect to modifiable factors that might be
      targeted for early intervention. The present work examines that parenting
      behaviors may operate as mediators, moderators, or independent influences on the
      development of youth depressive symptoms. One hundred one mothers and their early
      adolescent children participated in positive and negative interaction tasks.
      Maternal and youth self-reports of youth depressive symptoms were collected at
      baseline, 9-month, and 18-month assessments. Maternal history of depression was
      significantly associated with maternal-reported, but not youth self-reported,
      depressive symptomatology. Maternal positive and negative interaction behaviors
      in positive contexts were associated with higher youth self-reported depressive
      symptoms. Maternal positive interaction behaviors in positive contexts and
      maternal negative interactive behaviors in conflict contexts were associated with
      higher youth self-reported depressive symptoms. We found no evidence for maternal
      interaction behaviors serving as a mediator and little evidence of maternal
      interaction behaviors serving as a moderator of the relationship between maternal
      and offspring depression. Low maternal positive engagement tended to be more
      consistently associated with maternal- and self-reported youth depressive
      symptoms. The present findings suggest that characteristics of mother-child
      interactions that are associated with youth depressive symptomatology are
      pertinent to youth with and without a mother with a history of depression.

PMID- 25581088
TI  - The psychology of intelligence analysis: drivers of prediction accuracy in world
      politics.
AB  - This article extends psychological methods and concepts into a domain that is as
      profoundly consequential as it is poorly understood: intelligence analysis. We
      report findings from a geopolitical forecasting tournament that assessed the
      accuracy of more than 150,000 forecasts of 743 participants on 199 events
      occurring over 2 years. Participants were above average in intelligence and
      political knowledge relative to the general population. Individual differences in
      performance emerged, and forecasting skills were surprisingly consistent over
      time. Key predictors were (a) dispositional variables of cognitive ability,
      political knowledge, and open-mindedness; (b) situational variables of training
      in probabilistic reasoning and participation in collaborative teams that shared
      information and discussed rationales (Mellers, Ungar, et al., 2014); and (c)
      behavioral variables of deliberation time and frequency of belief updating. We
      developed a profile of the best forecasters; they were better at inductive
      reasoning, pattern detection, cognitive flexibility, and open-mindedness. They
      had greater understanding of geopolitics, training in probabilistic reasoning,
      and opportunities to succeed in cognitively enriched team environments. Last but
      not least, they viewed forecasting as a skill that required deliberate practice,
      sustained effort, and constant monitoring of current affairs.

PMID- 25581089
TI  - Advertising energy saving programs: The potential environmental cost of
      emphasizing monetary savings.
AB  - Many consumers have monetary or environmental motivations for saving energy.
      Indeed, saving energy produces both monetary benefits, by reducing energy bills,
      and environmental benefits, by reducing carbon footprints. We examined how
      consumers' willingness and reasons to enroll in energy-savings programs are
      affected by whether advertisements emphasize monetary benefits, environmental
      benefits, or both. From a normative perspective, having 2 noteworthy kinds of
      benefit should not decrease a program's attractiveness. In contrast,
      psychological research suggests that adding external incentives to an
      intrinsically motivating task may backfire. To date, however, it remains unclear
      whether this is the case when both extrinsic and intrinsic motivations are
      inherent to the task, as with energy savings, and whether removing explicit
      mention of extrinsic motivation will reduce its importance. We found that
      emphasizing a program's monetary benefits reduced participants' willingness to
      enroll. In addition, participants' explanations about enrollment revealed less
      attention to environmental concerns when programs emphasized monetary savings,
      even when environmental savings were also emphasized. We found equal attention to
      monetary motivations in all conditions, revealing an asymmetric attention to
      monetary and environmental motives. These results also provide practical guidance
      regarding the positioning of energy-saving programs: emphasize intrinsic
      benefits; the extrinsic ones may speak for themselves.

PMID- 25581090
TI  - Synthesis and biological studies of the thiols-triggered anticancer prodrug for a
      more effective cancer therapy.
AB  - A novel anticancer prodrug compound 1, which was designed to be triggered by
      thiols and release the chemotherapeutic agent mechlorethamine, was successfully
      prepared and evaluated for the first time. The activation of compound 1 was
      determined by NMR analysis and denaturing alkaline agarose gel electrophoresis. A
      fluorescence image and comet assay indicated that the inducible reactivity of 1
      could be accomplished in cell media. The anticancer activities are also
      discussed.

PMID- 25581091
TI  - A rare case of tension pneumocephalus post-cochlear implantation.

PMID- 25581092
TI  - Toward large scale roll-to-roll production of fully printed perovskite solar
      cells.
AB  - Fully printed perovskite solar cells are demonstrated with slot-die coating, a
      scalable printing method. A sequential slot-die coating process is developed to
      produce efficient perovskite solar cells and to be used in a large-scale roll-to
      roll printing process. All layers excluding the electrodes are printed and
      devices demonstrate up to 11.96% power conversion efficiency. It is also
      demonstrated that the new process can be used in roll-to-roll production. 

PMID- 25581093
TI  - Informed consent in medical decision-making in commercial gestational surrogacy:
      a mixed methods study in New Delhi, India.
AB  - OBJECTIVE: To investigate ethical issues in informed consent for decisions
      regarding embryo transfer and fetal reduction in commercial gestational
      surrogacy. DESIGN: Mixed methods study employing observations, an interview-guide
      and semi-structured interviews. SETTING: Fertility clinics and agencies in Delhi,
      India, between December 2011 and December 2012. POPULATION: Doctors providing
      conceptive technologies to commissioning couples and carrying out surrogacy
      procedures; surrogate mothers; agents functioning as links for surrogacy.
      METHODS: Interviews using semi-structured interview guides were carried out among
      20 doctors in 18 fertility clinics, five agents from four agencies and 14
      surrogate mothers. Surrogate mothers were interviewed both individually and in
      the presence of doctors and agents. Data on socio-economic context and
      experiences among and between various actors in the surrogacy process were coded
      to identify categories of ethical concern. Numerical and grounded theory-oriented
      analyses were used. MAIN OUTCOME MEASURES: Informed consent, number of embryos
      transferred, fetal reduction, conflict of interest among the involved parties.
      RESULTS: None of the 14 surrogate mothers were able to explain the risks involved
      in embryo transfer and fetal reduction. The majority of the doctors took
      unilateral decisions about embryo transfer and fetal reduction. The commissioning
      parents were usually only indirectly involved. In the qualitative analysis,
      difficulties in explaining procedures, autonomy, self-payment of fertility
      treatment and conflicts of interest were the main themes. CONCLUSIONS: Clinical
      procedural decisions were primarily made by the doctors. Surrogate mothers were
      not adequately informed. There is a need for regulation on decision-making
      procedures to safeguard the interests of surrogate mothers.

PMID- 25581094
TI  - Effect of a neck collar on upper airway size in children sedated with propofol
      midazolam combination during magnetic resonance imaging.
AB  - INTRODUCTION: Propofol and midazolam are widely used for pediatric magnetic
      resonance imaging (MRI) sedation. Increasing depth of sedation may be associated
      with airway obstruction. A neck collar supporting the mandible and maintaining
      the head in slight extension may be beneficial in maintaining airway patency. AIM
      OF THE STUDY: Primary aim: To assess upper airway size with and without a neck
      collar during pediatric MRI sedation with propofol-midazolam. Secondary aim: To
      evaluate complications encountered during the procedure. MATERIALS AND METHODS:
      Sixty patients aged 2-4 years scheduled for MRI of the brain were selected. They
      were sedated with intramuscular midazolam 0.1 mg.kg(-1) 30 min before the
      procedure. Patients were sedated with i.v. propofol 1 mg.kg(-1) and continued
      with 50-100 MUg.kg(-1) .min(-1) . T1 3D fast-field echo axial sequence from the
      nasopharyngeal roof to subglottic region was taken with and without application
      of a neck collar. Airway dimensions were measured and analyzed at the base of the
      tongue, soft palate, and at the epiglottis. RESULTS: At the base of the tongue
      and soft palate, the cross-sectional area (CSA) and the anteroposterior diameter
      of the airway were respectively statistically significantly higher when the neck
      collar was applied. The CSA at the epiglottis was significantly less with
      application of the neck collar. Complications were not significantly different
      between the two sequences. CONCLUSION: Application of a soft neck collar in
      children aged 2-4 years may enhance the retropalatal and retroglossal airway
      dimensions during pediatric sedation in the supine position.

PMID- 25581096
TI  - Isoflavones and their effects on the onset of puberty in male Wistar rats.
AB  - This study was performed to determine how two of the most important isoflavones,
      genistein and daidzein, affect the gonadal axis in male prepuberal rats. One
      hundred and seventy-five prepuberal male Wistar rats were allocated into seven
      groups: one control group and six experimental groups that were orally
      administered a high or low dose of genistein, daidzein or a mixture of both.
      Testosterone determination was assayed by EIA. The testes and body weights were
      measured, and the histology of the epididymis with the sperm content and
      epididymal sperm count were evaluated. In the control group, we observed an
      increase in the serum testosterone levels (>2.5 ng ml(-1) ) at the third week (52
      days), which corresponded to the onset of puberty in these rats. The same
      increase in serum testosterone levels was observed at the fourth week in rats
      that received low doses of isoflavones; therefore, we concluded that the onset of
      puberty was delayed. At high doses, there was no significant increase in
      testosterone levels, which could be related to the fact that these male rats did
      not reach puberty. These findings were supported by the results obtained from the
      analysis of the epididymal content as well as the testes/body weight ratio.

PMID- 25581095
TI  - Knockdown of hypothalamic RFRP3 prevents chronic stress-induced infertility and
      embryo resorption.
AB  - Whereas it is well established that chronic stress induces female reproductive
      dysfunction, whether stress negatively impacts fertility and fecundity when
      applied prior to mating and pregnancy has not been explored. In this study, we
      show that stress that concludes 4 days prior to mating results in persistent and
      marked reproductive dysfunction, with fewer successful copulation events, fewer
      pregnancies in those that successfully mated, and increased embryo resorption.
      Chronic stress exposure led to elevated expression of the hypothalamic inhibitory
      peptide, RFamide-related peptide-3 (RFRP3), in regularly cycling females.
      Remarkably, genetic silencing of RFRP3 during stress using an inducible-targeted
      shRNA completely alleviates stress-induced infertility in female rats, resulting
      in mating and pregnancy success rates indistinguishable from non-stress controls.
      We show that chronic stress has long-term effects on pregnancy success, even post
      stressor, that are mediated by RFRP3. This points to RFRP3 as a potential
      clinically relevant single target for stress-induced infertility. 

PMID- 25581097
TI  - Effects of Eichhornia crassipes and Ceratophyllum demersum on Soil and Water
      Environments and Nutrient Removal in Wetland Microcosms.
AB  - Wetland plants are important components that influence the biogeochemistry of
      wetland ecosystems. Therefore, remediation performance in wetlands can differ
      depending on the growth forms of plants. In this study, the effects of Eichhornia
      crassipes (floating plant) and Ceratophyllum demersum (submerged plant) on the
      wetland soil and water environments were investigated using a microcosm study
      with simulated hydrology of retention-type wetlands between rainfall events. The
      C. demersum microcosm (SP) showed the fastest recovery with a diel fluctuation
      pattern of dissolved oxygen, pH, and oxidation-reduction potential (ORP) from the
      impacts of nutrient inflow. Moreover, SP exhibited the lowest decrease in
      sediment ORP, the highest dehydrogenase activity, and more organic forms of
      nitrogen and phosphorus. E. crassipes microcosms exhibited the lowest water
      temperature, and efficiently controlled algae. In the presence of plants, the
      total nitrogen and phosphorus concentrations in water rapidly decreased, and the
      composition of organic and inorganic nutrient forms was altered along with a
      decrease in concentration. The results indicate that wetland plants help retain
      nutrients in the system, but the effects varied based on the wetland plant growth
      forms.

PMID- 25581098
TI  - Fe3W3C/WC/graphitic carbon ternary nanojunction hybrids for dye-sensitized solar
      cells.
AB  - Fe3 W3 C/WC/graphitic carbon (GC) ternary nanojunction hybrids are synthesized
      through a solid-state pyrolysis process for dye-sensitized solar cells (DSSCs).
      First-principles calculations have been first employed to investigate the
      adsorption energy between I3 (-) and Fe3 W3 C and WC nanoclusters. Scanning
      Kelvin probe images indicate that the work function changes greatly due to the
      formation of ternary nanojunctions, which favor fast photoelectron transfer. A
      photoelectrical conversion efficiency of 7.1 % is achieved based on Fe3 W3
      C/WC/GC hybrid counter electrodes, which is much higher than those of pure GC
      (5.02 %) and WC/GC hybrids (6.11 %). It has been further revealed that Fe3 W3
      C/WC/GC hybrid counter electrodes exhibit the best catalytic performances
      according to relevant electrochemical measurements, which can be attributed to
      fast photoelectron transfer due to the ternary junctions and the addition of Fe3
      W3 C with more catalytic metallic atoms. 

PMID- 25581099
TI  - Computational and biochemical design of a nanopore cleavable by a cancer-secreted
      enzyme.
AB  - Many proteinaceous macromolecules selectively transport substrates across lipid
      bilayers and effectively serve as gated nanopores. Here, we engineered cleavage
      site motifs for human matrix metalloprotease 7 (MMP-7) into the extracellular and
      pore-constricting loops of OprD, a bacterial substrate-specific transmembrane
      channel. Concurrent removal of two extracellular loops allowed MMP-7 to access
      and hydrolyze a cleavage-site motif engineered within the pore's major
      constricting loop, in both membrane-incorporated and detergent-solubilized OprDs.
      Import of antibiotics by the engineered OprDs into living bacteria pointed to
      their proper folding and integration in biological membranes. Purified engineered
      OprDs were also found to be properly folded in detergent. Hence, this study
      demonstrates the design of nanopores with a constriction cleavable by tumor
      secreted enzymes (like MMP-7) for their potential incorporation in lipid-based
      nanoparticles to accelerate drug release at the tumor site. 

PMID- 25581101
TI  - Early and mid-term postoperative outcome of inflammatory abdominal aortic
      aneurysms.
AB  - INTRODUCTION AND OBJECTIVES: The aim of this study is to report our experience on
      the postoperative outcome of surgical treatment of inflammatory abdominal aortic
      aneurysm (IAAA). MATERIALS AND METHODS: Between January 1997 and March 2014, 35
      patients with IAAA underwent surgery. The mean age was 63 +/- 18 years. Chronic
      renal failure was identified in 11 (31.4%) patients, and ischemic heart disease
      was confirmed in 15 (43%) patients. The mean aortic aneurysm diameter was 68 +/-
      25 mm. The abdominal aorta was clamped above the renal arteries in 6 (17%)
      patients. RESULTS: The hospital mortality was 5.7% (2 patients). Three patients
      developed an aortic pseudoaneurysm and underwent reoperation. Another patient
      developed a femoral anastomotic pseudoaneurysm 7 years after operation, which was
      treated surgically. The overall reoperation-free actuarial survival at 1, 5, and
      7 years was 94, 62, and 50%, respectively. The Cox model revealed the delta
      erythrocyte sedimentation rate (p = 0.002), ischemic heart disease (p = 0.006),
      and renal failure (p = 0.036) as strong predictors for poor overall outcome.
      CONCLUSION: Early postoperative outcome in terms of mortality and morbidity seems
      acceptable; however, patients with IAAA have an increased risk for reoperation
      due to pseudoaneurysm formation. Strong predictors for poor overall outcome seem
      to be elevated erythrocyte sedimentation rate, ischemic heart disease, and
      chronic renal failure.

PMID- 25581100
TI  - Self-assembly of DNA nanohydrogels with controllable size and stimuli-responsive
      property for targeted gene regulation therapy.
AB  - Here, we report the synthesis and characterization of size-controllable and
      stimuli-responsive DNA nanohydrogels as effective targeted gene delivery vectors.
      DNA nanohydrogels were created through a self-assembly process using three kinds
      of building units, respectively termed Y-shaped monomer A with three sticky ends
      (YMA), Y-shaped monomer B with one sticky end (YMB), and DNA linker (LK) with two
      sticky ends. Hybridization at the sticky ends of monomers and LK leads to
      nanohydrogel formation. DNA nanohydrogels are size-controllable by varying the
      ratio of YMA to YMB. By incorporating different functional elements, such as
      aptamers, disulfide linkages, and therapeutic genes into different building
      units, the synthesized aptamer-based nanohydrogels (Y-gel-Apt) can be used for
      targeted and stimuli-responsive gene therapy. Y-gel-Apt strongly inhibited cell
      proliferation and migration in target A549 cells, but not in control cells. By
      taking advantage of facile modular design and assembly, efficient cellular
      uptake, and superior biocompatibility, this Y-gel-Apt holds great promise as a
      candidate for targeted gene or drug delivery and cancer therapy. 

PMID- 25581102
TI  - Clinical Application of Fully Covered Self-Expandable Metal Stents in the
      Treatment of Bronchial Fistula.
AB  - Background The study was designed to access the feasibility, safety, and efficacy
      of fully covered self-expandable metal stents in the treatment of bronchial
      fistula. Methods Clinical data of nine patients (seven males and two females) who
      were treated with placement of tracheobronchial or bronchial fully covered self
      expandable metal stents from August 2005 to November 2011 were analyzed
      retrospectively. Among these patients, seven were diagnosed with bronchopleural
      fistula, one with tracheopleural fistula, and one with left main
      bronchoesophageal fistula. Eight had accompanying thoracic empyema. The fistula
      orifices ranged from 3.5 mm to 25 mm in diameter. All patients received topical
      anesthesia. L-shaped stents were placed in six patients and I-shaped stents in
      three under fluoroscopic guidance. After stent placement, patients with empyema
      were treated with pleural lavage. Results Stent placement in the tracheobronchial
      tree was successful in all patients, without procedure-related complications. The
      operating time was 5 to 16 minutes. A small amount of bubble overflowed from the
      intrathoracic drainage tube of only one patient. In the other patients, the
      bubble in the intrathoracic drainage tube disappeared immediately or angiography
      showed no overflow of contrast agent from the fistula orifice. The effective rate
      of fistula orifice closure after stent placement was 100%, with 88.9% rated as
      excellent. One patient coughed the stent out 5 days after placement and hence a
      new stent was placed. Among the patients with empyema, one died of septicemia
      arising from empyema on day 8 and another died of brain metastases of lung cancer
      6 months after stent insertion with persistent empyema. In the other six
      patients, empyema resolved after 2 to 5 months (cure rate 75%). Seven patients
      were followed up for 3 to 36 months. During follow-up, one stent was removed 8
      months after implantation due to difficult expectoration, without recurrent
      empyema. The remaining patients tolerated the stents well. The stents remained
      stable without migration or empyema recurrence, and they could eat and drink
      well. Conclusion The use of fully covered self-expandable metal stents is a safe,
      effective, and fast minimally invasive method to treat bronchial fistula,
      especially for selected cases with empyema. 

PMID- 25581103
TI  - Glassy-state stabilization of a dominant negative inhibitor anthrax vaccine
      containing aluminum hydroxide and glycopyranoside lipid A adjuvants.
AB  - During transport and storage, vaccines may be exposed to temperatures outside of
      the range recommended for storage, potentially causing efficacy losses. To better
      understand and prevent such losses, dominant negative inhibitor (DNI), a
      recombinant protein antigen for a candidate vaccine against anthrax, was
      formulated as a liquid and as a glassy lyophilized powder with the adjuvants
      aluminum hydroxide and glycopyranoside lipid A (GLA). Freeze-thawing of the
      liquid vaccine caused the adjuvants to aggregate and decreased its immunogenicity
      in mice. Immunogenicity of liquid vaccines also decreased when stored at 40
      degrees C for 8 weeks, as measured by decreases in neutralizing antibody titers
      in vaccinated mice. Concomitant with efficacy losses at elevated temperatures,
      changes in DNI structure were detected by fluorescence spectroscopy and increased
      deamidation was observed by capillary isoelectric focusing (cIEF) after only 1
      week of storage of the liquid formulation at 40 degrees C. In contrast, upon
      lyophilization, no additional deamidation after 4 weeks at 40 degrees C and no
      detectable changes in DNI structure or reduction in immunogenicity after 16 weeks
      at 40 degrees C were observed. Vaccines containing aluminum hydroxide and GLA
      elicited higher immune responses than vaccines adjuvanted with only aluminum
      hydroxide, with more mice responding to a single dose.

PMID- 25581104
TI  - Revisiting the usefulness of thromboxane-A2 modulation in the treatment of
      bronchoconstriction in asthma.
AB  - Airway smooth muscle (ASM) is the effector cell in the bronchoconstrictory
      pathway. It is believed that the bronchoconstriction present in asthma is
      associated with changes in the airway milieu that affect ASM excitation
      contraction coupling and Ca(2+)-handling. Asthmatics also react differently to
      ventilatory mechanical strain. Deep inspiration (DI), which produces
      bronchodilation in healthy individuals, is less effective in asthmatics, and even
      enhances bronchoconstriction in moderate to severely affected patients. Our
      laboratory has previously studied the mechanotransductory pathway of airway
      stretch-activated contractions (Rstretch) leading to DI-induced
      bronchoconstriction. We demonstrated the ability of agonists acting through
      thromboxane A2 (TxA2) receptors to amplify airway Rstretch responses. Despite the
      involvement of excitatory prostanoids in bronchoconstriction, clinical trials on
      treatments targeting TxA2-synthase inhibition and TP-receptor antagonism have
      produced mixed results. Studies in Western populations produced mostly negative
      results, whereas studies performed in Asian populations showed mostly positive
      outcomes. In this review, we discuss the role of TxA2-synthase inhibition and TP
      receptor antagonism in the treatment of asthmatics. We present information
      regarding variations in study designs and the possible role of TP-receptor gene
      polymorphisms in previous study outcome discrepancies. Perhaps future studies
      should focus on asthmatic patients with DI-induced bronchoconstriction in
      particular, planting the seed for the individualized treatments for asthmatics. 

PMID- 25581105
TI  - The long-term influence of repetitive cellular cardiac rejections on left
      ventricular longitudinal myocardial deformation in heart transplant recipients.
AB  - The aim of the study was to evaluate the long-term influence of repeated acute
      cellular rejections on left ventricular longitudinal deformation in heart
      transplantation (HTX) patients. One hundred and seventy-eight HTX patients were
      included in the study. Rejections were classified according to the International
      Society of Heart and Lung Transplantation (ISHLT) classification (0R-3R).
      Patients were divided into three groups according to rejection scores (RSs).
      Group 1: <50% of biopsies with 1R rejection and no >=2R rejections; Group 2:
      >=50% of biopsies with 1R rejection or one biopsy with >=2R rejection; Group 3:
      >=Two biopsies with >=2R rejections. All patients had a comprehensive
      echocardiographic examination and coronary angiography. We found significantly
      decreasing global longitudinal strain (GLS) comparing to rejection groups (GLS
      group 1: -16.8 +/- 2.4 (%); GLS group 2: -15.9 +/- 3.3 (%); GLS group 3: -14.5 +/
      2.9 (%), P = 0.0003). After excluding patients with LVEF < 50% or vasculopathy,
      GLS was still significantly reduced according to RS groups (P = 0.0096). Total
      number of 1R and 2R rejections correlated significant to GLS in a linear
      regression model. In contrast, we found fractional shortening and LVEF to be
      unaffected by repeated rejections. In conclusion, repeated cardiac rejections
      lead to impaired graft function as detected by decreasing magnitude of GLS. In
      contrast, traditional systolic graft function surveillance by LVEF did not
      correlate to rejection burden. 

PMID- 25581106
TI  - Drugs for chronic heart failure.

PMID- 25581107
TI  - Metreleptin (Myalept): a leptin analog for generalized lipodystrophy.

PMID- 25581109
TI  - The genetic basis of population fecundity prediction across multiple field
      populations of Nilaparvata lugens.
AB  - Identifying the molecular markers for complex quantitative traits in natural
      populations promises to provide novel insight into genetic mechanisms of
      adaptation and to aid in forecasting population dynamics. In this study, we
      investigated single nucleotide polymorphisms (SNPs) using candidate gene approach
      from high- and low-fecundity populations of the brown planthopper (BPH)
      Nilaparvata lugens Stal (Hemiptera: Delphacidae) divergently selected for
      fecundity. We also tested whether the population fecundity can be predicted by a
      few SNPs. Seven genes (ACE, fizzy, HMGCR, LpR, Sxl, Vg and VgR) were inspected
      for SNPs in N. lugens, which is a serious insect pest of rice. By direct
      sequencing of the complementary DNA and promoter sequences of these candidate
      genes, 1033 SNPs were discovered within high- and low-fecundity BPH populations.
      A panel of 121 candidate SNPs were selected and genotyped in 215 individuals from
      2 laboratory populations (HFP and LFP) and 3 field populations (GZP, SGP and
      ZSP). Prior to association tests, population structure and linkage disequilibrium
      (LD) among the 3 field populations were analysed. The association results showed
      that 7 SNPs were significantly associated with population fecundity in BPH. These
      significant SNPs were used for constructing general liner models with stepwise
      regression. The best predictive model was composed of 2 SNPs (ACE-862 and VgR-816
      ) with very good fitting degree. We found that 29% of the phenotypic variation in
      fecundity could be accounted for by only two markers. Using two laboratory
      populations and a complete independent field population, the predictive accuracy
      was 84.35-92.39%. The predictive model provides an efficient molecular method to
      predict BPH fecundity of field populations and provides novel insights for insect
      population management. 

PMID- 25581110
TI  - Reduction of functionalized tertiary phosphine oxides with BH3.
AB  - A direct stereoselective conversion of tertiary hydroxyalkylphosphine oxides to
      the corresponding tertiary hydroxyalkylphosphine-boranes involving facile
      reduction of the P?O bond by BH3 under mild conditions has been developed. The
      unprecedented facility of reduction of the strong P?O bond by BH3, a mild
      reducing agent, has been achieved through an intramolecular P?O...B complexation
      directed by proximal alpha- or beta-hydroxy groups present in the phosphine oxide
      structures. As established by two chemical correlations, the developed
      transformation of hydroxyalkylphosphine oxides into hydroxyalkylphosphine-boranes
      takes place with complete inversion of configuration at P. 

PMID- 25581108
TI  - Trends in oral anticoagulant choice for acute stroke patients with nonvalvular
      atrial fibrillation in Japan: the SAMURAI-NVAF study.
AB  - BACKGROUND: Large clinical trials are lack of data on non-vitamin K antagonist
      oral anticoagulants for acute stroke patients. AIM: To evaluate the choice of
      oral anticoagulants at acute hospital discharge in stroke patients with
      nonvalvular atrial fibrillation and clarify the underlying characteristics
      potentially affecting that choice using the multicenter Stroke Acute Management
      with Urgent Risk-factor Assessment and Improvement-NVAF registry
      (ClinicalTrials.gov NCT01581502). METHOD: The study included 1192 acute ischemic
      stroke/transient ischemic attack patients with nonvalvular atrial fibrillation
      (527 women, 77.7 +/- 9.9 years old) between September 2011 and March 2014, during
      which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were
      approved for clinical use. Oral anticoagulant choice at hospital discharge
      (median 23-day stay) was assessed. RESULTS: Warfarin was chosen for 650 patients,
      dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10
      month observation periods, patients taking warfarin gradually decreased to 46.5%
      and those taking nonvitamin K antagonist oral anticoagulants increased to 48.0%.
      As compared with warfarin users, patients taking nonvitamin K antagonist oral
      anticoagulants included more men, were younger, more frequently had small
      infarcts, and had lower scores for poststroke CHADS2 , CHA2 DS2 -VASc, and HAS
      BLED, admission National Institutes of Health stroke scale, and discharge
      modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started
      at a median of four-days after stroke onset without early intracranial
      hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier
      had smaller infarcts and lower scores for the admission National Institutes of
      Health stroke scale and the discharge modified Rankin Scale than those starting
      later. Choice of nonvitamin K antagonist oral anticoagulants was independently
      associated with 20-day or shorter hospitalization (OR 2.46, 95% CI 1.87-3.24).
      CONCLUSIONS: Warfarin use at acute hospital discharge was still common in the
      initial years after approval of nonvitamin K antagonist oral anticoagulants,
      although nonvitamin K antagonist oral anticoagulant users increased gradually.
      The index stroke was milder and ischemia-risk indices were lower in nonvitamin K
      antagonist oral anticoagulant users than in warfarin users. Early initiation of
      nonvitamin K antagonist oral anticoagulants seemed safe.

PMID- 25581111
TI  - How to optimize hepatitis C virus treatment impact on life years saved in
      resource-constrained countries.
AB  - In resource-constrained countries where the prevalence of hepatitis C virus (HCV)
      disease is usually high, it is important to know which population should be
      treated first in order to increase treatment effectiveness. The aim was to
      estimate the effectiveness of different HCV treatment eligibility scenarios in
      three different countries. Using a Markov model, we estimated the number of life
      years saved (LYS) with different treatment eligibility scenarios according to
      fibrosis stage (F1-F4 or F3-4), compared to base case (F2-F4), at a constant
      treatment rate, of patients between 18 and 60 years of age, at stages F0/F1 to
      F4, without liver complications or coinfections, chronically infected by HCV, and
      treated with pegylated interferon (IFN)/ribavirin or more-efficacious therapies
      (i.e. IFN free). We conducted the analysis in Egypt (prevalence = 14.7%; 45,000
      patients treated/year), Thailand (prevalence = 2.2%; 1,000 patients
      treated/year), and Cote d'Ivoire (prevalence = 3%; 150 patients treated/year). In
      Egypt, treating F1 patients in addition to >=F2 patients (SE1 vs. SE0) decreased
      LYS by 3.9%. Focusing treatment only on F3-F4 patients increased LYS by 6.7% (SE2
      vs. SE0). In Thailand and Cote d'Ivoire, focusing treatment only on F3-F4
      patients increased LYS by 15.3% and 11.0%, respectively, compared to treating
      patients >=F2 (ST0 and SC0, respectively). Treatment only for patients at stages
      F3-F4 with IFN-free therapies would increase LYS by 16.7% versus SE0 in Egypt,
      22.0% versus ST0 in Thailand, and 13.1% versus SC0 in Cote d'Ivoire. In this
      study, we did not take into account the yearly new infections and the impact of
      treatment on HCV transmission. CONCLUSION: Our model-based analysis demonstrates
      that prioritizing treatment in F3-F4 patients in resource-constrained countries
      is the most effective scenario in terms of LYS, regardless of treatment
      considered.

PMID- 25581112
TI  - Quality of life one year post-Shiga toxin-producing Escherichia coli O104
      infection--a prospective cohort study.
AB  - BACKGROUND: In 2011, a major outbreak of hemolytic-uremic syndrome (HUS) and
      bloody diarrhea related to infections from Shiga toxin-producing Escherichia coli
      O104 (STEC) occurred in Germany. While previous research has focused on the
      medical components of this disease, we aimed to investigate the course of health
      related quality of life (HrQoL) over 12 months including somatic and psychosocial
      risk factors. Furthermore, the influence of chronic fatigue (CF) on HrQoL was
      examined. METHODS: A prospective cohort study with n = 389 patients completing
      self-report scales at baseline, after 6 months (participation rate: 79%) and
      after 12 months (participation rate: 77%). The courses of physical and mental
      HrQoL over the 12 month period were calculated by employing general linear mixed
      models. KEY RESULTS: While the physical component score of HrQoL reached a score
      comparable to the general population, the mental component score remained below
      average 12 months after STEC infection. Female gender, prior psychiatric
      disorder, and prior traumatic events were risk factors for a worse HrQoL course
      after 12 months, while social support was identified to be protective. CF was
      associated with low HrQoL. In addition, the somatic symptom burden remained
      persistently high. CONCLUSIONS & INFERENCES: Our results show high somatic and
      psychosocial burden in patients 12 months after STEC infection. We recommend
      considering the risk factors and protective factors of poor HrQoL early in the
      treatment of STEC or similar diseases. Patients who are suffering from persisting
      somatic symptoms, CF, and impaired HrQoL may require specific aftercare.

PMID- 25581115
TI  - Attorneys aim to reform "compassionate use": groups say the regulatory system
      lags behind scientific advances.

PMID- 25581114
TI  - Establishing versus preserving impressions: Predicting success in the multiple
      audience problem.
AB  - People sometimes seek to convey discrepant impressions of themselves to different
      audiences simultaneously. Research suggests people are generally successful in
      this "multiple audience problem." Adding to previous research, the current
      research sought to examine factors that may limit this success by measuring
      social anxiety and placing participants into situations requiring them to either
      establish or preserve multiple impressions simultaneously. In general,
      participants were more successful when preserving previously conveyed impressions
      than when establishing impressions for the first time. In contrast, social
      anxiety did not affect multiple audience success. In all, this research offers
      valuable insight into potential challenges that people face in many social
      situations. 

PMID- 25581116
TI  - Urine HPV test could offer a noninvasive alternative.

PMID- 25581113
TI  - Circulating follicular helper-like T cells in systemic lupus erythematosus:
      association with disease activity.
AB  - OBJECTIVE: To assess circulating follicular helper T (Tfh)-like CD4+ T cells in
      patients with systemic lupus erythematosus (SLE) and determine their relationship
      to disease activity. METHODS: Blood samples from patients with SLE, as well as
      blood samples from patients with Behcet's disease (BD) and healthy individuals as
      controls, were analyzed. In all samples, circulating Tfh-like cells were
      enumerated by flow cytometry, using, as markers, expression of CXCR5, inducible T
      cell costimulator (ICOS), and programmed death 1 (PD-1) protein, as well as
      secretion of interleukin-21 (IL-21). The frequency of circulating Tfh-like cells
      was compared to that of circulating plasmablasts (CD19+IgD-CD38+). In addition,
      the possible association of circulating Tfh-like cells with the SLE Disease
      Activity Index (SLEDAI) was evaluated. RESULTS: The subset of circulating Tfh
      like T cells, identified as CXCR5(high) ICOS(high) PD-1(high) , was expanded in
      the blood of SLE patients compared to controls. Circulating Tfh-like cells were
      found to produce IL-21 and had lower expression of CCR7 as compared to that in
      circulating CXCR5(high) central memory T cells, thereby enabling their
      distinction. Expression of PD-1, but not ICOS or CXCR5, was significantly
      elevated in circulating Tfh-like cells from SLE patients compared to controls. PD
      1 expression among CXCR5(high) circulating Tfh-like cells correlated with the
      SLEDAI, frequency of circulating plasmablasts, and anti-double-stranded DNA
      antibody positivity, but not with disease duration or past organ injury; rather,
      this cell profile appeared to be a reflection of current active disease.
      CONCLUSION: Circulating Tfh-like cells are associated with disease activity in
      SLE, suggesting that their presence indicates abnormal homeostasis of T cell-B
      cell collaboration, with a causal relationship that is central to disease
      pathogenesis. These findings also suggest that circulating Tfh-like cells provide
      a surrogate for aberrant germinal center activity in SLE, and that their PD-1
      expression offers a tool for measuring disease activity and monitoring the
      response to therapies.

PMID- 25581117
TI  - Women aged 75 years and older benefit from mammography.

PMID- 25581118
TI  - Surface plasmon coupled emission in micrometer-scale cells: a leap from interface
      to bulk targets.
AB  - Surface plasmon coupled emission (SPCE) technique has attracted increasing
      attention in biomolecular interaction analysis and cell imaging because of its
      high sensitivity, low detection volume and low fluorescence background.
      Typically, the working range of SPCE is limited at nanometers to an interface.
      For micrometer-scale samples, new SPCE properties are expected because of complex
      coupling modes. In this work, cells with different subregions labeled were
      studied using a SPCE spectroscopy system. Angular and p-polarized emission was
      observed for cell membrane, cytoplasm, and nucleus labeled with DiI, Nile Red,
      and propidium iodide, respectively. The SPCE signals were always partially p
      polarized, and the maximum emission angle did not shift, regardless of variations
      in emission wavelength, fluorophore distribution and stained layer thickness.
      Additionally, increased polarization and a broader angle distribution were also
      observed with an increase in sample thickness. We also investigated the impact of
      metallic substrates on the SPCE properties of cells. Compared with Au and Ni
      substrates, Al substrates presented better polarization and angle distribution.
      Moreover, the real-time detection of the cell labeling process was achieved by
      monitoring SPCE intensity. These findings expand SPCE from a surface technique to
      a 3D method for investigating bulk targets beyond the nanoscale interfaces,
      providing a basis to apply this technique to study cell membrane fluidity and
      biomolecule interactions inside the cell and to distinguish between cell
      subregions. 

PMID- 25581119
TI  - How the Irish savoured gastroenterology: a literary reinterpretation of the
      alternative history.

PMID- 25581121
TI  - The influence of the capping agent on the oxidation of silver nanoparticles: nano
      impacts versus stripping voltammetry.
AB  - The influence of capping agents on the oxidation of silver nanoparticles was
      studied by using the electrochemical techniques of anodic stripping voltammetry
      and anodic particle coulometry ("nano-impacts"). Five spherical silver
      nanoparticles each with a different capping agent (branched polyethylenimine
      (BPEI), citrate, lipoic acid, polyethylene glycol (PEG) and polyvinylpyrrolidone
      (PVP)) were used to perform comparative experiments. In all cases, regardless of
      the capping agent, complete oxidation of the single nanoparticles was seen in
      anodic particle coulometry. The successful quantitative detection of the silver
      nanoparticle size displays the potential application of anodic particle
      coulometry for nanoparticle characterisation. In contrast, for anodic stripping
      voltammetry using nanoparticles drop casting, it was observed that the capping
      agent has a very significant effect on the extent of silver oxidation. All five
      samples gave a low oxidative charge corresponding to partial oxidation. It is
      concluded that the use of anodic stripping voltammetry to quantify nanoparticles
      is unreliable, and this is attributed to nanoparticle aggregation. 

PMID- 25581120
TI  - Cardiovascular risk profile at the onset of psoriatic arthritis: a population
      based cohort study.
AB  - OBJECTIVE: The role of cardiovascular disease (CVD) risk factors in psoriatic
      arthritis (PsA) is poorly understood. We examined the prevalence of CVD risk
      factors at initial onset of PsA and compared the observed incidence of CVD events
      with that predicted by the Framingham Risk Score (FRS) to determine its
      applicability in this patient population. METHODS: A population-based incidence
      cohort of 158 patients with PsA who fulfilled Classification of Psoriatic
      Arthritis criteria for PsA in 1989-2008 was assembled. Medical records were
      reviewed to ascertain CVD risk factors and CVD events. Future risk of CVD was
      estimated using the FRS algorithm. RESULTS: Mean age was 43.4 years (range 19-74
      years), 61% were men, and 44% were obese (body mass index >=30 kg/m(2) ). Fifty
      four patients (34%) presented with >=2 CVD risk factors at PsA incidence. Among
      126 patients ages >=30 years at PsA incidence with no prior history of CVD, 33%
      had an FRS >=10%, with 11% having an FRS >=20%, and 18 experienced a CVD event in
      the first 10 years of disease duration. The 10-year cumulative incidence of CVD
      events was 17% (95% confidence interval [95% CI] 10%-24%), almost twice as high
      as the predicted incidence based on the FRS (standardized incidence ratio 1.80,
      95% CI 1.14-2.86; P = 0.012). CONCLUSION: The majority of newly diagnosed PsA
      patients have a >10% risk of CVD within 10 years of PsA incidence. The CVD risk
      in these patients is higher than expected and underestimated by the FRS.

PMID- 25581122
TI  - Rhythmic control of mRNA stability modulates circadian amplitude of mouse Period3
      mRNA.
AB  - The daily oscillations observed in most living organisms are endogenously
      generated with a period of 24 h, and the underlying structure of periodic
      oscillation is an autoregulatory transcription-translation feedback loop. The
      mechanisms of untranslated region (UTR)-mediated post-transcriptional regulation
      (e.g., mRNA degradation and internal ribosomal entry site (IRES)-mediated
      translation) have been suggested to fine-tune the expression of clock genes.
      Mouse Period3 (mPer3) is one of the paralogs of Period gene and its function is
      important in peripheral clocks and sleep physiology. mPer3 mRNA displays a
      circadian oscillation as well as a circadian phase-dependent stability, while the
      stability regulators still remain unknown. In this study, we identify three
      proteins - heterogeneous nuclear ribonucleoprotein (hnRNP) K, polypyrimidine
      tract-binding protein (PTB), and hnRNP D - that bind to mPer3 mRNA 3'-UTR. We
      show that hnRNP K is a stabilizer that increases the amplitude of circadian mPer3
      mRNA oscillation and hnRNP D is a destabilizer that decreases it, while PTB
      exhibits no effect on mPer3 mRNA expression. Our experiments describe their
      cytoplasmic roles for the mRNA stability regulation and the circadian amplitude
      formation. Moreover, our mathematical model suggests a mechanism through which
      post-transcriptional mRNA stability modulation provides not only the flexibility
      of oscillation amplitude, but also the robustness of the period and the phase for
      circadian mPer3 expression. Mouse Period3 (mPer3) is one of well-known clock
      genes. We identified three 3'-UTR-binding proteins that modulate the mRNA
      stability, and they influenced to the amplitude of circadian mPer3 mRNA
      oscillation. Our mathematical model not only showed the relationship between mRNA
      stability and its oscillation profile but provided the molecular mechanism for
      the robustness of the period and the phase in circadian oscillation. hnK,
      heterogeneous nuclear ribonucleoprotein (hnRNP) K; hnD, hnRNP D; PTB,
      polypyrimidine tract-binding protein. 

PMID- 25581123
TI  - Clinical documentation to improve patient care.

PMID- 25581125
TI  - Alleviation mechanisms against hepatocyte oxidative stress in patients with
      chronic hepatic disorders.
AB  - AIM: Autophagy induction and Mallory-Denk body (MDB) formation have been
      considered to have cytoprotective effects from cellular stress in liver diseases.
      We investigated the relations among oxidative stress, autophagy and MDB formation
      in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non
      alcoholic fatty liver disease (NAFLD) to clarify the alleviation mechanisms
      against oxidative stress of hepatocytes. METHODS: First, we treated cultured
      cells with proteasome inhibitor (PI) or free fatty acid (FFA) and evaluated
      endoplasmic reticulum (ER) stress, oxidative stress, ubiquitinated proteins and
      p62 by western blotting. Then, we used human liver biopsy samples to evaluate
      oxidative stress, autophagy and MDB formation by immunohistochemical analysis.
      RESULTS: Treatment with PI or FFA increased ER stress, oxidative stress,
      ubiquitinated proteins and p62 in cultured cells. Human liver biopsy samples of
      CHC and NAFLD showed that MDB formed in areas with strong oxidative stress and
      that the MDB-containing cells circumvented oxidative stress. Keratin 8 (K8)
      expression was strong in MDB-containing cells in CHC and NAFLD. However, in CHB
      samples, the expression of K8 was not increased in response to oxidative stress
      and MDB aggregates did not appear. Aminotransferase values were significantly
      lower in patients with CHC and NAFLD in whom light chain 3 antibody expression
      was increased in response to oxidative stress. CONCLUSION: Strong expression of
      K8 was considered to be important for MDB formation. MDB protect liver cells from
      oxidative stress at a cellular level and autophagy reduced hepatic damage when it
      was induced in the hepatocytes exposed to strong oxidative stress.

PMID- 25581127
TI  - Carbonic anhydrase inhibitors with dual-tail moieties to match the hydrophobic
      and hydrophilic halves of the carbonic anhydrase active site.
AB  - We present a new approach to carbonic anhydrase II (CA II) inhibitor design that
      enables close interrogation of the regions of the CA active site where there is
      the greatest variability in amino acid residues among the different CA isozymes.
      By appending dual tail groups onto the par excellence CA inhibitor acetazolamide,
      compounds that may interact with the distinct hydrophobic and hydrophilic halves
      of the CA II active site were prepared. The dual-tail combinations selected
      included (i) two hydrophobic moieties, (ii) two hydrophilic moieties, and (iii)
      one hydrophobic and one hydrophilic moiety. The CA enzyme inhibition profile as
      well as the protein X-ray crystal structure of compound 3, comprising one
      hydrophobic and one hydrophilic tail moiety, in complex with CA II is described.
      This novel dual-tail approach has provided an enhanced opportunity to more fully
      exploit interactions with the CA active site by enabling these molecules to
      interact with the distinct halves of the active site. In addition to the dual
      tail compounds, a corresponding set of single-tail derivatives was synthesized,
      enabling a comparative analysis of the single-tail versus dual-tail compound CA
      inhibition profile. 

PMID- 25581124
TI  - Genetic influences can protect against unresponsive parenting in the prediction
      of child social competence.
AB  - Although social competence in children has been linked to the quality of
      parenting, prior research has typically not accounted for genetic similarities
      between parents and children, or for interactions between environmental (i.e.,
      parental) and genetic influences. In this article, the possibility of a Gene x
      Environment (G * E) interaction in the prediction of social competence in school
      age children is evaluated. Using a longitudinal, multimethod data set from a
      sample of children adopted at birth (N = 361), a significant interaction was
      found between birth parent sociability and sensitive, responsive adoptive
      parenting when predicting child social competence at school entry (age 6), even
      when controlling for potential confounds. An analysis of the interaction revealed
      that genetic strengths can buffer the effects of unresponsive parenting. 

PMID- 25581126
TI  - NADPH Oxidase-Dependent NLRP3 Inflammasome Activation and its Important Role in
      Lung Fibrosis by Multiwalled Carbon Nanotubes.
AB  - The purpose of this paper is to elucidate the key role of NADPH oxidase in NLRP3
      inflammasome activation and generation of pulmonary fibrosis by multi-walled
      carbon nanotubes (MWCNTs). Although it is known that oxidative stress plays a
      role in pulmonary fibrosis by single-walled CNTs, the role of specific sources of
      reactive oxygen species, including NADPH oxidase, in inflammasome activation
      remains to be clarified. In this study, three long aspect ratio (LAR) materials
      (MWCNTs, single-walled carbon nanotubes, and silver nanowires) are used to
      compare with spherical carbon black and silver nanoparticles for their ability to
      trigger oxygen burst activity and NLRP3 assembly. All LAR materials but not
      spherical nanoparticles induce robust NADPH oxidase activation and respiratory
      burst activity in THP-1 cells, which are blunted in p22(phox) -deficient cells.
      The NADPH oxidase is directly involved in lysosomal damage by LAR materials, as
      demonstrated by decreased cathepsin B release and IL-1beta production in
      p22(phox) -deficient cells. Reduced respiratory burst activity and inflammasome
      activation are also observed in bone marrow-derived macrophages from p47(phox) 
      deficient mice. Moreover, p47(phox) -deficient mice have reduced IL-1beta
      production and lung collagen deposition in response to MWCNTs. Lung fibrosis is
      also suppressed by N-acetyl-cysteine in wild-type animals exposed to MWCNTs. 

PMID- 25581129
TI  - Categorizing wildlife responses to urbanization and conservation implications of
      terminology.

PMID- 25581128
TI  - Social integration confers thermal benefits in a gregarious primate.
AB  - Sociality has been shown to have adaptive value for gregarious species, with more
      socially integrated animals within groups experiencing higher reproductive
      success and longevity. The value of social integration is often suggested to
      derive from an improved ability to deal with social stress within a group; other
      potential stressors have received less attention. We investigated the
      relationship between environmental temperature, an important non-social stressor,
      and social integration in wild female vervet monkeys (Chlorocebus pygerythrus),
      using implanted data loggers to obtain direct measures of core body temperature.
      Heterothermy (as measured by 24-h amplitude of body temperature) increased, and
      24-h minima of body temperature decreased, as the 24-h minimum ambient
      temperature decreased. As winter progressed, monkeys became increasingly
      heterothermic and displayed lower 24-h minima of body temperature. Monkeys with a
      greater number of social partners displayed a smaller 24-h amplitude (that is,
      were more homoeothermic) and higher 24-h minima of body temperature (that is,
      became less hypothermic), than did animals with fewer social partners. Our
      findings demonstrate that social integration has a direct influence on
      thermoregulatory ability: individual animals that form and maintain more social
      relationships within their group experience improved thermal competence compared
      to those with fewer social relationships. Given the likely energetic consequences
      of thermal benefits, our findings offer a viable physiological explanation that
      can help account for variations in fitness in relation to individual differences
      in social integration. 

PMID- 25581130
TI  - Real time measurement of PEG shedding from lipid nanoparticles in serum via NMR
      spectroscopy.
AB  - Small interfering RNA (siRNA) is a novel therapeutic modality that benefits from
      nanoparticle mediated delivery. The most clinically advanced siRNA-containing
      nanoparticles are polymer-coated supramolecular assemblies of siRNA and lipids
      (lipid nanoparticles or LNPs), which protect the siRNA from nucleases, modulate
      pharmacokinetics of the siRNA, and enable selective delivery of siRNA to target
      cells. Understanding the mechanisms of assembly and delivery of such systems is
      complicated by the complexity of the dynamic supramolecular assembly as well as
      by its subsequent interactions with the biological milieu. We have developed an
      ex vivo method that provides insight into how LNPs behave when contacted with
      biological fluids. Pulsed gradient spin echo (PGSE) NMR was used to directly
      measure the kinetics of poly(ethylene) glycol (PEG) shedding from siRNA
      encapsulated LNPs in rat serum. The method represents a molecularly specific,
      real-time, quantitative, and label-free way to monitor the behavior of a
      nanoparticle surface coating. We believe that this method has broad implications
      in gaining mechanistic insights into how nanoparticle-based drug delivery
      vehicles behave in biofluids and is versatile enough to be applied to a diversity
      of systems. 

PMID- 25581132
TI  - Springing forward to medium-term results for endobronchial coils for emphysema.

PMID- 25581131
TI  - Methane-derived carbon flow through microbial communities in arctic lake
      sediments.
AB  - Aerobic methane (CH4 ) oxidation mitigates CH4 release and is a significant
      pathway for carbon and energy flow into aquatic food webs. Arctic lakes are
      responsible for an increasing proportion of global CH4 emissions, but CH4
      assimilation into the aquatic food web in arctic lakes is poorly understood.
      Using stable isotope probing (SIP) based on phospholipid fatty acids (PLFA-SIP)
      and DNA (DNA-SIP), we tracked carbon flow quantitatively from CH4 into sediment
      microorganisms from an arctic lake with an active CH4 seepage. When 0.025 mmol
      CH4 g(-1) wet sediment was oxidized, approximately 15.8-32.8% of the CH4 -derived
      carbon had been incorporated into microorganisms. This CH4 -derived carbon
      equated to up to 5.7% of total primary production estimates for Alaskan arctic
      lakes. Type I methanotrophs, including Methylomonas, Methylobacter and
      unclassified Methylococcaceae, were most active at CH4 oxidation in this arctic
      lake. With increasing distance from the active CH4 seepage, a greater diversity
      of bacteria incorporated CH4 -derived carbon. Actinomycetes were the most
      quantitatively important microorganisms involved in secondary feeding on CH4 
      derived carbon. These results showed that CH4 flows through methanotrophs into
      the broader microbial community and that type I methanotrophs, methylotrophs and
      actinomycetes are important organisms involved in using CH4 -derived carbon in
      arctic freshwater ecosystems.

PMID- 25581133
TI  - Nanoscale sub-100 picosecond all-optical magnetization switching in GdFeCo
      microstructures.
AB  - Ultrafast magnetization reversal driven by femtosecond laser pulses has been
      shown to be a promising way to write information. Seeking to improve the
      recording density has raised intriguing fundamental questions about the
      feasibility of combining ultrafast temporal resolution with sub-wavelength
      spatial resolution for magnetic recording. Here we report on the experimental
      demonstration of nanoscale sub-100 ps all-optical magnetization switching,
      providing a path to sub-wavelength magnetic recording. Using computational
      methods, we reveal the feasibility of nanoscale magnetic switching even for an
      unfocused laser pulse. This effect is achieved by structuring the sample such
      that the laser pulse, via both refraction and interference, focuses onto a
      localized region of the structure, the position of which can be controlled by the
      structural design. Time-resolved photo-emission electron microscopy studies
      reveal that nanoscale magnetic switching employing such focusing can be pushed to
      the sub-100 ps regime.

PMID- 25581135
TI  - Identifying evaluation considerations for the recovery and restoration from the
      2010 Gulf of Mexico oil spill: An initial appraisal of stakeholder concerns and
      values.
AB  - Understanding what can be achieved and what should be avoided by environmental
      management decisions requires an understanding of values, or what is cared about
      in a decision. Decision analysis provides tools and processes for constructing
      objectives that transparently reflect the values being considered in
      environmental management decisions. The present study demonstrates parts of the
      initial decision analysis steps for identifying a decision context and
      constructing objectives for the recovery and long-term restoration of the Gulf of
      Mexico following the 2010 Deepwater Horizon oil spill. From a review of multiple
      reports, including those developed by policy makers and nongovernmental
      organizations, a preliminary structuring of concerns and considerations into
      objectives was derived to highlight features of importance in the recovery from
      the spill and long-term restoration. The fundamental objectives constructed for
      the long-term restoration context reflect broader concerns regarding well-being
      and quality of life. When developed through stakeholder engagement processes,
      clarifying objectives can potentially 1) lend insight into the values that can be
      affected, 2) meaningfully include stakeholders in the decision-making process, 3)
      enhance transparency and communication, and 4) develop high-impact management
      strategies reflecting broad public interests. This article is a US government
      work and is in the public domain in the United States of America.

PMID- 25581134
TI  - The effect of early in-hospital medication review on health outcomes: a
      systematic review.
AB  - AIMS: Adverse drug events are an important cause of emergency department visits,
      unplanned admissions and prolonged hospital stays. Our objective was to
      synthesize the evidence on the effect of early in-hospital pharmacist-led
      medication review on patient-oriented outcomes based on observed data. METHODS:
      We systematically searched eight bibliographic reference databases, electronic
      grey literature, medical journals, conference proceedings, trial registries and
      bibliographies of relevant papers. We included studies that employed random or
      quasi-random methods to allocate subjects to pharmacist-led medication review or
      control. Medication review had to include, at a minimum, obtaining a best
      possible medication history and reviewing medications for appropriateness and
      adverse drug events. The intervention had to be initiated within 24 h of
      emergency department presentation or 72 h of admission. We extracted data in
      duplicate and pooled outcomes from clinically homogeneous studies of the same
      design using random effects meta-analysis. RESULTS: We retrieved 4549 titles of
      which seven were included, reporting the outcomes of 3292 patients. We pooled
      data from studies of the same design, and found no significant differences in
      length of hospital admission (weighted mean difference [WMD] -0.04 days, 95%
      confidence interval [CI] -1.63, 1.55), mortality (odds ratio [OR] 1.09, 95% CI
      0.69, 1.72), readmissions (OR 1.15, 95% CI 0.81, 1.63) or emergency department
      revisits at 3 months (OR 0.60, 95% CI 0.27, 1.32). Two large studies reporting
      reductions in readmissions could not be included in our pooled estimates due to
      differences in study design. CONCLUSIONS: Wide confidence intervals suggest that
      additional research is likely to influence the effect size estimates and clarify
      the effect of medication review on patient-oriented outcomes. This systematic
      review failed to identify an effect of pharmacist-led medication review on health
      outcomes.

PMID- 25581136
TI  - Therapeutic follow-up of Lichen Planopilaris using in vivo reflectance confocal
      microscopy: a case report.

PMID- 25581137
TI  - Laser nano- and micro-structuring of silicon using a laser-induced plasma for
      beam conditioning.
AB  - A technique based on the interaction between a laser pulse and a laser-induced
      plasma is proposed as a very simple and potentially powerful method for surface
      nanostructuring. A laser pulse was focused onto a metallic target in order to
      generate a plasma, while a second laser pulse was directed to the plasma and
      crossed it perpendicularly to the first pulse and, subsequently, hit a silicon
      substrate. In this conditions, the second pulse interacts with the plasma which
      acted as an optical element whose properties could be modified by varying the
      energy density of the first pulse or the delay between the two pulses.
      Microscopic analysis carried out on the silicon surface revealed a wide variety
      of nanostructured patterns. 

PMID- 25581138
TI  - Risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart
      failure: a nested case-control study in UK general practice.
AB  - AIMS: The aim of this study was to identify risk factors for hyperkalaemia in a
      cohort of patients with newly diagnosed heart failure in the UK. METHODS AND
      RESULTS: A nested case-control study was conducted using data from The Health
      Improvement Network primary care database. A cohort of 19 194 patients aged 1-89
      years between January 2000 and December 2005 with newly diagnosed heart failure
      was followed up and cases of hyperkalaemia identified. Cases were frequency
      matched to controls by age, sex, and calendar year, and information on
      demographics, co-morbidities, co-medications, and lifestyle factors was extracted
      from the database. Using unconditional logistic regression models, odds ratios
      (ORs) with 95% confidence intervals (CIs) were calculated to identify potential
      risk factors. In total, 2176 hyperkalaemia cases were identified over a mean
      follow-up of 3.9 years. Significant risk factors for hyperkalaemia were: renal
      failure (OR 3.81; 95% CI 3.29-4.42), type II diabetes (OR 1.52; 95% CI 1.31
      1.75), valvular heart disease (OR 1.28; 95% CI 1.06-1.54), and current use of
      potassium-sparing diuretics (OR 3.01; 95% CI 2.61-3.48), ACE inhibitors (OR 1.70;
      95% CI 1.41-2.04), trimethoprim (OR 2.82; 95% CI 1.88-4.23), non-steroidal anti
      inflammatory drugs (OR 1.41; 95% CI 1.11-1.79), and several drug combinations.
      The risk was highest within the first month of medication use and decreased
      thereafter. CONCLUSION: Our findings may help to better identify patients with
      heart failure most likely to benefit from careful monitoring of serum potassium
      levels. Particular vigilance is needed during the start of treatment with certain
      medications.

PMID- 25581139
TI  - i Engaging user testing: lessons learned from inpatients and health care
      providers.
AB  - This user-testing study assessed the feasibility of the functional prototype of
      an innovative fall prevention intervention, i Engaging, to engage patients in
      their own fall prevention care during hospital stays. The i Engaging application
      as well as its approaches to engage patients in fall prevention care during
      hospital stays was perceived as being easy to use, effective, and practical. The
      user-testing study consisted of adults 65 years of age or older and health care
      providers. 

PMID- 25581140
TI  - Overt and occult vidian canal involvement in juvenile angiofibroma and its
      possible impact on recurrence.
AB  - BACKGROUND: Postexcision residual disease in the vidian canal is speculated to
      contribute to recurrence in juvenile angiofibroma. METHODS: We composed a
      prospective cohort of 16 consecutive patients with juvenile angiofibroma (stages
      IIA-IIIB). The presurgical vidian canal assessment was done by contrast-enhanced
      CT (1.2 mm collimation). At surgery after complete tumor excision, the vidian
      canal tissue was sampled for histology. Postexcision drilling of the vidian canal
      was done in 8 of 15 patients to remove microscopic residual disease, with a 24 to
      48 month follow-up period. RESULTS: Presurgical radiology indicated ipsilateral
      vidian canal enlargement (>=3 mm)/destruction in 13 of 16 patients.
      Radiologically occult involvement was documented only by histology in another 1
      of 16 patients. Postexcision sampling of the vidian canal noted microscopic
      residual tumor in 3 of 15 patients. No recurrences were noted in 8 cases (0 of 8)
      with postexcision drilling of the vidian canal and 2 recurrences in 7 cases (2 of
      7) with no drilling (p = .20). CONCLUSION: Vidian canal involvement in juvenile
      angiofibroma is almost universal (14 of 16) and may be occult to CT evaluation.
      The site may harbor microscopic residual tumor after seemingly complete excision.
      Surgical attention toward it may reduce recurrences. (c) 2015 Wiley Periodicals,
      Inc. Head Neck 38: E421-425, 2016.

PMID- 25581141
TI  - Shade affects responses to drought and flooding - acclimation to multiple
      stresses in bittersweet (Solanum dulcamara L.).
AB  - Plants exposed to environmental stress often respond by a change in their
      phenotypic traits. These changes in trait expression may alleviate the negative
      effect of such stress factors. However, if multiple stresses are present,
      responses are likely to be less predictable and hence do not necessarily
      correlate to plant performance. This study tested if this expectation was true,
      by subjecting Solanum dulcamara plants to various simultaneous stress factors.
      Plants were grown in well-watered conditions, drought or flooding, and exposed to
      either full light or shade for 4 weeks. Shoot and root biomass, stem
      morphological parameters, such as height, number of nodes and length of stem
      internodes, and leaf traits like length, specific leaf area, chlorophyll content
      and stomatal conductance were determined. Both variation in light and in water
      availability typically caused slower growth, and resulted in distinct phenotypic
      changes in stem, leaf and root traits. However, effects of stresses on the
      expression of traits were not always additive. Instead, some combined stress
      responses (e.g. leaf size) appeared to be limited by physical or physiological
      constraints, whereas other responses were opposite to each other (e.g. root:shoot
      ratio), resulting in an intermediate phenotype in the combined stress treatment.
      These data suggest that in natural conditions, where combined stress factors are
      likely to be present, the optimal phenotype may not necessarily be expressed.
      Responses of plants to multiple stress factors may therefore not be associated
      with immediate advantages in terms of increased performance.

PMID- 25581142
TI  - Breakdown of middle lamella pectin by (?) OH during rapid abscission in Azolla.
AB  - Azolla, a small water fern, abscises its roots and branches within 30 min upon
      treatment with various stresses. This study was conducted to test whether, in the
      rapid abscission that occurs in Azolla, breakdown of wall components of
      abscission zone cells by (?) OH is involved. Experimentally generated (?) OH
      caused the rapid separation of abscission zone cells from detached roots and the
      rapid shedding of roots from whole plants. Electron microscopic observations
      revealed that (?) OH rapidly and selectively dissolved a well-developed middle
      lamella between abscission zone cells and resultantly caused rapid cell
      separation and shedding. Treatment of abscission zones of Impatiens leaf petiole
      with (?) OH also accelerated the separation of abscission zone cells. However,
      compared with that of Azolla roots, accelerative effects in Impatiens were weak.
      A large amount of (?) OH was cytochemically detected in abscission zone cells
      both of Azolla roots and of Impatiens leaf petioles. These results suggest that
      (?) OH is involved in the cell separation process not only in the rapid
      abscission in Azolla but also in the abscission of Impatiens. However, for rapid
      abscission to occur, a well-developed middle lamella, a unique structure, which
      is sensitive to the attack of (?) OH, might be needed.

PMID- 25581143
TI  - The impact of toxins on the developing brain.
AB  - The impact of toxins on the developing brain is usually subtle for an individual
      child, but the damage can be substantial at the population level. Numerous
      challenges must be addressed to definitively test the impact of toxins on brain
      development in children: We must quantify exposure using a biologic marker or
      pollutant; account for an ever-expanding set of potential confounders; identify
      critical windows of vulnerability; and repeatedly examine the association of
      biologic markers of toxins with intellectual abilities, behaviors, and brain
      function in distinct cohorts. Despite these challenges, numerous toxins have been
      implicated in the development of intellectual deficits and mental disorders in
      children. Yet, too little has been done to protect children from these ubiquitous
      but insidious toxins. The objective of this review is to provide an overview on
      the population impact of toxins on the developing brain and describe implications
      for public health. 

PMID- 25581144
TI  - The prescription opioid and heroin crisis: a public health approach to an
      epidemic of addiction.
AB  - Public health authorities have described, with growing alarm, an unprecedented
      increase in morbidity and mortality associated with use of opioid pain relievers
      (OPRs). Efforts to address the opioid crisis have focused mainly on reducing
      nonmedical OPR use. Too often overlooked, however, is the need for preventing and
      treating opioid addiction, which occurs in both medical and nonmedical OPR users.
      Overprescribing of OPRs has led to a sharp increase in the prevalence of opioid
      addiction, which in turn has been associated with a rise in overdose deaths and
      heroin use. A multifaceted public health approach that utilizes primary,
      secondary, and tertiary opioid addiction prevention strategies is required to
      effectively reduce opioid-related morbidity and mortality. We describe the scope
      of this public health crisis, its historical context, contributing factors, and
      lines of evidence indicating the role of addiction in exacerbating morbidity and
      mortality, and we provide a framework for interventions to address the epidemic
      of opioid addiction. 

PMID- 25581145
TI  - Stress and type 2 diabetes: a review of how stress contributes to the development
      of type 2 diabetes.
AB  - Current policy and research around type 2 diabetes (T2D) interventions largely
      invoke a behavioral model. We suggest that activation of the physiologic stress
      response (PSR) from chronic exposure to stressors, low socioeconomic status
      (SES), severe mental health problems, or aggressive behavior increases the risk
      of T2D. This article is a comprehensive review of the literature on the link
      between T2D and psychosocial factors focusing on prospective studies of the risk
      for developing diabetes. The review found an increased risk for T2D in people:
      exposed to stressful working conditions or traumatic events; with depression;
      with personality traits or mental health problems that put them in conflict with
      others; of low SES, either currently or in childhood; and in racial/ethnic
      minority populations, independent of current SES. This review suggests that T2D
      prevention research would be more effective if (a) the PSR to psychosocial
      factors (especially social disparities) was recognized and (b) intervention
      programs evaluated reduction in social disparities as part of a comprehensive
      approach. 

PMID- 25581146
TI  - Translating evidence into population health improvement: strategies and barriers.
AB  - Among the challenges facing research translation-the effort to move evidence into
      policy and practice-is that key questions chosen by investigators and funders may
      not always align with the information priorities of decision makers, nor are the
      findings always presented in a form that is useful for or relevant to the
      decisions at hand. This disconnect is a problem particularly for population
      health, where the change agents who can make the biggest difference in improving
      health behaviors and social and environmental conditions are generally
      nonscientists outside of the health professions. To persuade an audience that
      does not read scientific journals, strong science may not be enough to elicit
      change. Achieving influence in population health often requires four ingredients
      for success: research that is responsive to user needs, an understanding of the
      decision-making environment, effective stakeholder engagement, and strategic
      communication. This article reviews the principles and provides examples from a
      national and local initiative. 

PMID- 25581147
TI  - Using new technologies to improve the prevention and management of chronic
      conditions in populations.
AB  - Lifestyle factors are important in the development of chronic diseases, such as
      heart disease, respiratory disease, and diabetes, and chronic disease risk can be
      reduced by changes in lifestyle behaviors linked to these conditions. The use of
      mass media and community-wide strategies targeting these behaviors has been
      extensively evaluated since the 1970s. This review summarizes some examples of
      interventions and their use of media conducted within the old communications
      landscape of the 1970s and 1980s and the key lessons learned from their design,
      implementation, and evaluation. We then consider the potential and evidence base
      for using contemporary technology applications and platforms-within the new
      communications landscape-to improve the prevention and management of lifestyle
      related chronic diseases in the future. We discuss the implications and
      adaptation of lessons derived from the ways in which new technologies are being
      used in commercial and political contexts and their relevance for public health.
      Finally, we consider some recent examples of applying new technologies to public
      health issues and consider some of the challenges in this rapidly developing
      field. 

PMID- 25581148
TI  - What is health resilience and how can we build it?
AB  - Whether a community is in the path of a natural disaster, the target of an act of
      terror, or simply striving to meet the demands of increasingly dense urban
      populations, a community resilience paradigm can help communities and individuals
      not just to mitigate damage and heal, but to thrive. This article discusses
      experiences from recent, large-scale disasters to explore how community
      resilience might serve as a sustainable paradigm for organizing public health and
      medical preparedness, response, and recovery. By strengthening health systems,
      meeting the needs of vulnerable populations, and promoting organizational
      competence, social connectedness, and psychological health, community resilience
      encourages actions that build preparedness, promote strong day-to-day systems,
      and address the underlying social determinants of health. Thus, community
      resilience resonates with a wide array of stakeholders, particularly those whose
      work routinely addresses health, wellness, or societal well-being. 

PMID- 25581149
TI  - Cross-sector partnerships and public health: challenges and opportunities for
      addressing obesity and noncommunicable diseases through engagement with the
      private sector.
AB  - Over the past few decades, cross-sector partnerships with the private sector have
      become an increasingly accepted practice in public health, particularly in
      efforts to address infectious diseases in low- and middle-income countries. Now
      these partnerships are becoming a popular tool in efforts to reduce and prevent
      obesity and the epidemic of noncommunicable diseases. Partnering with businesses
      presents a means to acquire resources, as well as opportunities to influence the
      private sector toward more healthful practices. Yet even though collaboration is
      a core principle of public health practice, public-private or nonprofit-private
      partnerships present risks and challenges that warrant specific consideration. In
      this article, we review the role of public health partnerships with the private
      sector, with a focus on efforts to address obesity and noncommunicable diseases
      in high-income settings. We identify key challenges-including goal alignment and
      conflict of interest-and consider how changes to partnership practice might
      address these. 

PMID- 25581150
TI  - Unintentional home injuries across the life span: problems and solutions.
AB  - Home injuries cause more than 30,000 deaths and 12 million nonfatal injuries
      annually in the United States. They generate an estimated $222 billion in
      lifetime costs annually. Despite some data limitations in documenting home as the
      location of an injury, much progress has been made in identifying effective
      prevention strategies that reduce injury or mitigate risk behaviors. The current
      interest in public health in the role of housing in health offers unparalleled
      opportunities for injury prevention professionals concerned with home injuries.
      Sharing the science of injury prevention with the wide array of professionals
      such as architects, home builders, home visitors, and fire and emergency medical
      services providers-who create home environments and interact with residents could
      be a useful approach. A collaborative national effort to reduce the burden of
      home injuries is needed. 

PMID- 25581151
TI  - Cure violence: a public health model to reduce gun violence.
AB  - Scholars and practitioners alike in recent years have suggested that real and
      lasting progress in the fight against gun violence requires changing the social
      norms and attitudes that perpetuate violence and the use of guns. The Cure
      Violence model is a public health approach to gun violence reduction that seeks
      to change individual and community attitudes and norms about gun violence. It
      considers gun violence to be analogous to a communicable disease that passes from
      person to person when left untreated. Cure Violence operates independently of,
      while hopefully not undermining, law enforcement. In this article, we describe
      the theoretical basis for the program, review existing program evaluations,
      identify several challenges facing evaluators, and offer directions for future
      research. 

PMID- 25581152
TI  - Effects of policies designed to keep firearms from high-risk individuals.
AB  - This article summarizes and critiques available evidence from studies published
      between 1999 and August 2014 on the effects of policies designed to keep firearms
      from high-risk individuals in the United States. Some prohibitions for high-risk
      individuals (e.g., those under domestic violence restraining orders, violent
      misdemeanants) and procedures for checking for more types of prohibiting
      conditions are associated with lower rates of violence. Certain laws intended to
      prevent prohibited persons from accessing firearms-rigorous permit-to-purchase,
      comprehensive background checks, strong regulation and oversight of gun dealers,
      and requiring gun owners to promptly report lost or stolen firearms-are
      negatively associated with the diversion of guns to criminals. Future research is
      needed to examine whether these laws curtail nonlethal gun violence and whether
      the effects of expanding prohibiting conditions for firearm possession are
      modified by the presence of policies to prevent diversion. 

PMID- 25581153
TI  - Lessons from complex interventions to improve health.
AB  - Complexity-resulting from interactions among many component parts-is a property
      of both the intervention and the context (or system) into which it is placed.
      Complexity increases the unpredictability of effects. Complexity invites new
      approaches to logic modeling, definitions of integrity and means of
      standardization, and evaluation. New metaphors and terminology are needed to
      capture the recognition that knowledge generation comes from the hands of
      practitioners/implementers as much as it comes from those usually playing the
      role of intervention researcher. Failure to acknowledge this may blind us to the
      very mechanisms we seek to understand. Researchers in clinical settings are
      documenting health improvement gains made as a consequence of complex systems
      thinking. Improvement science in clinical settings has much to offer researchers
      in population health. 

PMID- 25581155
TI  - The response of the US Centers for Disease Control and Prevention to the obesity
      epidemic.
AB  - The recognition of the obesity epidemic as a national problem began in 1999 with
      the Centers for Disease Control and Prevention's (CDC's) publication of a series
      of annual state-based maps that demonstrated the rapid changes in the prevalence
      of obesity. Increasing rates of obesity had been noted in earlier CDC studies,
      but the maps provided evidence of a rapid, nationwide increase. The urgent need
      to respond to the epidemic led to the identification of state targets and the
      first generation of interventions for obesity prevention and control. The CDC's
      role was to provide setting- and intervention-specific guidance on implementing
      these strategies, and to assess changes in targeted policies and behaviors. The
      CDC's efforts were augmented by Congressional funding for community initiatives
      to improve nutrition and increase physical activity. Complementary investments by
      Kaiser Permanente, the Robert Wood Johnson Foundation, and the Institute of
      Medicine improved the evidence base and provided policy recommendations that
      reinforced the need for a multisectoral approach. Legislative, regulatory, and
      voluntary initiatives enacted by President Obama's administration translated many
      of the strategies into effective practice. Whether current efforts to address
      obesity can be sustained will depend on whether they can be translated into
      greater grass-roots engagement consistent with a social movement. 

PMID- 25581156
TI  - Commentary: evidence to guide gun violence prevention in America.
AB  - Gun violence is a major threat to the public's health and safety in the United
      States. The articles in this volume's symposium on gun violence reveal the scope
      of the problem and new trends in mortality rates from gunfire. Leading scholars
      synthesize research evidence that demonstrates the ability of numerous policies
      and programs-each consistent with lessons learned from successful efforts to
      combat public health problems-to prevent gun violence. Each approach presents
      challenges to successful implementation. Future research should inform efforts to
      assess which approaches are most effective and how to implement evidence-based
      interventions most effectively. 

PMID- 25581157
TI  - Uses of electronic health records for public health surveillance to advance
      public health.
AB  - Public health surveillance conducted by health departments in the United States
      has improved in completeness and timeliness owing to electronic laboratory
      reporting. However, the collection of detailed clinical information about
      reported cases, which is necessary to confirm the diagnosis, to understand
      transmission, or to determine disease-related risk factors, is still heavily
      dependent on manual processes. The increasing prevalence and functionality of
      electronic health record (EHR) systems in the United States present important
      opportunities to advance public health surveillance. EHR data have the potential
      to further increase the breadth, detail, timeliness, and completeness of public
      health surveillance and thereby provide better data to guide public health
      interventions. EHRs also provide a unique opportunity to expand the role and
      vision of current surveillance efforts and to help bridge the gap between public
      health practice and clinical medicine. 

PMID- 25581154
TI  - Policy dilemmas in Latino health care and implementation of the Affordable Care
      Act.
AB  - The changing Latino demographic in the United States presents a number of
      challenges to health care policy makers, clinicians, organizations, and other
      stakeholders. Studies have demonstrated that Latinos tend to have worse patterns
      of access to, and utilization of, health care than other ethnic and racial
      groups. The implementation of the Affordable Care Act (ACA) of 2010 may
      ameliorate some of these disparities. However, even with the ACA, it is expected
      that Latinos will continue to have problems accessing and using high-quality
      health care, especially in states that are not expanding Medicaid eligibility as
      provided by the ACA. We identify four current policy dilemmas relevant to
      Latinos' health and ACA implementation: (a) the need to extend coverage to the
      undocumented; (b) the growth of Latino populations in states with limited
      insurance expansion; 

PMID- 25581160
TI  - Accuracy assessment of the linear Poisson-Boltzmann equation and
      reparametrization of the OBC generalized Born model for nucleic acids and nucleic
      acid-protein complexes.
AB  - The generalized Born model in the Onufriev, Bashford, and Case (Onufriev et al.,
      Proteins: Struct Funct Genet 2004, 55, 383) implementation has emerged as one of
      the best compromises between accuracy and speed of computation. For simulations
      of nucleic acids, however, a number of issues should be addressed: (1) the
      generalized Born model is based on a linear model and the linearization of the
      reference Poisson-Boltmann equation may be questioned for highly charged systems
      as nucleic acids; (2) although much attention has been given to potentials,
      solvation forces could be much less sensitive to linearization than the
      potentials; and (3) the accuracy of the Onufriev-Bashford-Case (OBC) model for
      nucleic acids depends on fine tuning of parameters. Here, we show that the
      linearization of the Poisson Boltzmann equation has mild effects on computed
      forces, and that with optimal choice of the OBC model parameters, solvation
      forces, essential for molecular dynamics simulations, agree well with those
      computed using the reference Poisson-Boltzmann model.

PMID- 25581159
TI  - Steady state is reached within 2-3 days of once-daily administration of degludec,
      a basal insulin with an ultralong duration of action.
AB  - BACKGROUND: Various factors influence the pharmacokinetic and pharmacodynamic
      properties of insulin analogs. The aim of the present study was to determine time
      to steady state of insulin degludec (IDeg), a basal insulin analog with an
      ultralong duration of action, after once-daily subcutaneous administration in
      subjects of varying age, diabetes type, and ethnicity. METHODS: Time to steady
      state was analyzed in 195 subjects across five Phase I randomized single-center
      double-blind studies: three in subjects with type 1 diabetes (T1DM), including
      one in elderly subjects, and two in subjects with type 2 diabetes (T2DM),
      including one with African American and Hispanic/Latino subpopulations. Subjects
      received once-daily IDeg (100 U/mL, s.c.) at doses of 0.4-0.8 U/kg for 6-12 days.
      Time to clinical steady state was measured from first dose until the serum IDeg
      trough concentration exceeded 90% of the final plateau level. The IDeg
      concentrations were log-transformed and analyzed using a mixed-effects model with
      time from first dose and dose level (where applicable) as fixed effects, and
      subject as a random effect. RESULTS: Steady state serum IDeg concentrations were
      reached after 2-3 days in all subjects. In trials with multiple dose levels, time
      to steady state was independent of dose level in T1DM (P = 0.51) and T2DM (P =
      0.75). CONCLUSIONS: Serum IDeg concentrations reached steady state within 2-3
      days of once-daily subcutaneous administration in all subjects with T1DM or T2DM,
      including elderly and African American and Hispanic/Latino subjects. At steady
      state, serum IDeg concentrations were unchanged from day to day.

PMID- 25581161
TI  - Development of a group-based self-management programme for individuals with
      chronic fatigue syndrome: a pilot study.
AB  - OBJECTIVE: The aim of the study was to develop a group-based self-management
      programme for individuals with chronic fatigue syndrome (CFS) by using the
      participants' experiences with the initial version of the programme, which
      intends to promote coping with the illness in a primary healthcare setting.
      METHODS: An initial programme was developed, based on self-efficacy theory and
      the concepts of client-centred practice and empowerment. Subsequently, the
      programme was tested and further developed by drawing on the participants'
      experiences with the programme. Focus-group interviews were applied. The
      interviews were analysed using thematic analysis. RESULTS: The initial programme
      was found to be feasible, although several modifications regarding the content
      and practical organization of the programme were proposed. CONCLUSION: In line
      with the participants' experiences, the final self-management programme was
      developed, which includes short presentations of eight topics, exchange of
      experiences among participants, goal-setting, construction of action plans, and
      relaxation exercises, in addition to a meeting for relatives. The programme will
      be provided in eight biweekly sessions and be led by juxtaposed peer counsellors
      and occupational therapists. The effects of the final programme will be evaluated
      in a randomized controlled trial.

PMID- 25581162
TI  - The Causal Effect of Education on Health: What is the Role of Health Behaviors?
AB  - We investigate the causal effect of education on health and the part of it that
      is attributable to health behaviors by distinguishing between short-run and long
      run mediating effects: whereas, in the former, only behaviors in the immediate
      past are taken into account, in the latter, we consider the entire history of
      behaviors. We use two identification strategies: instrumental variables based on
      compulsory schooling reforms and a combined aggregation, differencing, and
      selection on an observables technique to address the endogeneity of both
      education and behaviors in the health production function. Using panel data for
      European countries, we find that education has a protective effect for European
      men and women aged 50+. We find that the mediating effects of health behaviors
      measured by smoking, drinking, exercising, and the body mass index-account in the
      short run for around a quarter and in the long run for around a third of the
      entire effect of education on health.

PMID- 25581158
TI  - A subcutaneous adipose tissue-liver signalling axis controls hepatic
      gluconeogenesis.
AB  - The search for effective treatments for obesity and its comorbidities is of prime
      importance. We previously identified IKK-epsilon and TBK1 as promising
      therapeutic targets for the treatment of obesity and associated insulin
      resistance. Here we show that acute inhibition of IKK-epsilon and TBK1 with
      amlexanox treatment increases cAMP levels in subcutaneous adipose depots of obese
      mice, promoting the synthesis and secretion of the cytokine IL-6 from adipocytes
      and preadipocytes, but not from macrophages. IL-6, in turn, stimulates the
      phosphorylation of hepatic Stat3 to suppress expression of genes involved in
      gluconeogenesis, in the process improving glucose handling in obese mice.
      Preliminary data in a small cohort of obese patients show a similar association.
      These data support an important role for a subcutaneous adipose tissue-liver axis
      in mediating the acute metabolic benefits of amlexanox on glucose metabolism, and
      point to a new therapeutic pathway for type 2 diabetes. 

PMID- 25581163
TI  - Does inchinkoto, a herbal medicine, have hepatoprotective effects in major
      hepatectomy? A prospective randomized study.
AB  - OBJECTIVES: This randomized clinical trial was designed to investigate whether
      inchinkoto has a hepatoprotective effect on postoperative outcome after major
      hepatectomy. METHODS: Sixty-one patients scheduled for major hepatectomy were
      randomly assigned to one of two groups in which preoperative inchinkoto was
      (inchinkoto group, n = 30) or was not (non-inchinkoto group, n = 31)
      administered. Inchinkoto was administered for at least 7 days before surgery. The
      primary endpoint was the incidence of post-hepatectomy liver damage. The
      expression of nuclear factor E2-related factor 2 (Nrf2) and other oxygen stress
      related markers in the liver were also determined. RESULTS: There was no
      significant difference in clinical characteristics between the inchinkoto and non
      inchinkoto groups. Serum levels in liver function tests and incidences of post
      hepatectomy liver failure did not differ significantly between the two groups.
      However, there was a significantly higher induction of antioxidant factors in the
      liver, such as Nrf2 protein and heme oxygenase-1 mRNA, after hepatectomy in the
      inchinkoto group than in the non-inchinkoto group. CONCLUSIONS: The preoperative
      administration of inchinkoto did not have a significant impact on the overall
      outcome of major hepatectomy. However, inchinkoto induced the expression of Nrf2
      during hepatectomy and may have exerted an antioxidative effect on the liver.

PMID- 25581164
TI  - Crystal structure and functional analysis of MiD49, a receptor for the
      mitochondrial fission protein Drp1.
AB  - Mitochondrial fission requires recruitment of dynamin-related protein 1 (Drp1) to
      the mitochondrial surface, where assembly leads to activation of its GTP
      dependent scission function. MiD49 and MiD51 are two receptors on the
      mitochondrial outer membrane that can recruit Drp1 to facilitate mitochondrial
      fission. Structural studies indicated that MiD51 has a variant nucleotidyl
      transferase fold that binds an ADP co-factor essential for activation of Drp1
      function. MiD49 shares sequence homology with MiD51 and regulates Drp1 function.
      However, it is unknown if MiD49 binds an analogous co-factor. Because MiD49 does
      not readily crystallize, we used structural predictions and biochemical screening
      to identify a surface entropy reduction mutant that facilitated crystallization.
      Using molecular replacement, we determined the atomic structure of MiD49 to 2.4
      A. Like MiD51, MiD49 contains a nucleotidyl transferase domain; however, the
      electron density provides no evidence for a small-molecule ligand. Structural
      changes in the putative nucleotide-binding pocket make MiD49 incompatible with an
      extended ligand like ADP, and critical nucleotide-binding residues found in MiD51
      are not conserved. MiD49 contains a surface loop that physically interacts with
      Drp1 and is necessary for Drp1 recruitment to the mitochondrial surface. Our
      results suggest a structural basis for the differential regulation of MiD51-
      versus MiD49-mediated fission. 

PMID- 25581166
TI  - Determination of metal content in superoxide dismutase enzymes by capillary
      electrophoresis?.
AB  - Superoxide dismutases are antioxidant scavenger enzymes that contain a metal
      cofactor (copper, zinc, iron, and manganese) in their active site. Metal content
      measurement is one of the essential steps to characterize enzyme biological
      activity. We have developed a capillary electrophoretic protocol for the
      determination of the metal content in superoxide dismutase enzymes. The
      background electrolyte containing 10 mM pyridine-2,6-dicarboxylic acid and 1 mM 1
      methyl-3-tetradecylimidazolium chloride at pH 3.8 was optimized for on-column
      complexation of the above-mentioned metals. The minimum detectable levels of
      metals ranged from 0.3 to 1.2 MUg/mL. The reliability of the method was checked
      by parallel quantitative determination of the metal content in superoxide
      dismutase enzymes by graphite furnace or flame atomic absorption
      spectrophotometry methods. 

PMID- 25581165
TI  - Optical clearing in dense connective tissues to visualize cellular connectivity
      in situ.
AB  - Visualizing the three-dimensional morphology and spatial patterning of cells
      embedded deep within dense connective tissues of the musculoskeletal system has
      been possible only by utilizing destructive techniques. Here we utilize fructose
      based clearing solutions to image cell connectivity and deep tissue-scale
      patterning in situ by standard confocal microscopy. Optical clearing takes
      advantage of refractive index matching of tissue and the embedding medium to
      visualize light transmission through a broad range of bovine and whole mount
      murine tissues, including cartilage, bone, and ligament, of the head and
      hindlimb. Using non-destructive methods, we show for the first time intercellular
      chondrocyte connections throughout the bulk of cartilage, and we reveal in situ
      patterns of osteocyte processes and the lacunar-canalicular system deep within
      mineralized cortical bone. Optical clearing of connective tissues is expected to
      find broad application for the study of cell responses in normal physiology and
      disease pathology. 

PMID- 25581167
TI  - N-terminal pro-B-type natriuretic peptide, tricuspid jet flow velocity, and death
      in adults with sickle cell disease.

PMID- 25581168
TI  - The elastase-PK101 structure: mechanism of an ultrasensitive activity-based probe
      revealed.
AB  - Human neutrophil elastase (HNE) plays a central role in neutrophil host defense,
      but its broad specificity makes HNE a difficult target for both inhibitor and
      probe development. Recently, we identified the unnatural amino acid containing
      activity-based probe PK101, which exhibits astounding sensitivity and selectivity
      for HNE, yet completely lacks mechanistic explanation for its unique
      characteristics. Here, we present the crystal structure of the HNE-PK101 complex
      which not only reveals the basis for PK101 ultrasensitivity but also uncovers so
      far unrecognized HNE features. Strikingly, the Nle(O-Bzl) function in the P4
      position of PK101 reveals and leverages an "exo-pocket" on HNE as a critical
      factor for selectivity. Furthermore, the PK101 P3 position harbors a methionine
      dioxide function, which mimics a post-translationally oxidized methionine residue
      and forms a critical hydrogen bond to the backbone amide of Gly219 of HNE. Gly219
      resides in a Gly-Gly motif that is unique to HNE, yet compulsory for this
      interaction. Consequently, this feature enables HNE to accommodate substrates
      that have undergone methionine oxidation, which constitutes a hallmark post
      translational modification of neutrophil signaling. 

PMID- 25581169
TI  - HbNIN2, a cytosolic alkaline/neutral-invertase, is responsible for sucrose
      catabolism in rubber-producing laticifers of Hevea brasiliensis (para rubber
      tree).
AB  - In Hevea brasiliensis, an alkaline/neutral invertase (A/N-Inv) is responsible for
      sucrose catabolism in latex (essentially the cytoplasm of rubber-producing
      laticifers, the source of natural rubber) and implicated in rubber yield.
      However, neither the gene encoding this enzyme nor its molecular and biochemical
      properties have been well documented. Three Hevea A/N-Inv genes, namely HbNIN1, 2
      and 3, were first cloned and characterized in planta and in Escherichia coli.
      Cellular localizations of HbNIN2 mRNA and protein were probed. From latex, active
      A/N-Inv proteins were purified, identified, and explored for enzymatic
      properties. HbNIN2 was identified as the major A/N-Inv gene functioning in latex
      based on its functionality in E. coli, its latex-predominant expression, the
      conspicuous localization of its mRNA and protein in the laticifers, and its
      expressional correlation with rubber yield. An active A/N-Inv protein was
      partially purified from latex, and determined as HbNIN2. The enhancement of
      HbNIN2 enzymatic activity by pyridoxal is peculiar to A/N-Invs in other plants.
      We conclude that HbNIN2, a cytosolic A/N-Inv, is responsible for sucrose
      catabolism in rubber laticifers. The results contribute to the studies of sucrose
      catabolism in plants as a whole and natural rubber synthesis in particular. 

PMID- 25581171
TI  - "Analyses of black Aspergillus species of peanut and maize for ochratoxins and
      fumonisins," a comment on: J. Food Prot. 77(5):805-813 (2014).

PMID- 25581172
TI  - Response.

PMID- 25581173
TI  - Quantitative risk assessment of human salmonellosis and listeriosis related to
      the consumption of raw milk in Italy.
AB  - Two quantitative risk assessment (RA) models were developed to describe the risk
      of salmonellosis and listeriosis linked to consumption of raw milk sold in
      vending machines in Italy. Exposure assessment considered the official
      microbiological records monitoring raw milk samples from vending machines
      performed by the regional veterinary authorities from 2008 to 2011, microbial
      growth during storage, destruction experiments, consumption frequency of raw
      milk, serving size, and consumption preference. Two separate RA models were
      developed: one for the consumption of boiled milk and the other for the
      consumption of raw milk. The RA models predicted no human listeriosis cases per
      year either in the best or worst storage conditions and with or without boiling
      raw milk, whereas the annual estimated cases of salmonellosis depend on the dose
      response relationships used in the model, the milk storage conditions, and
      consumer behavior in relation to boiling raw milk or not. For example, the
      estimated salmonellosis cases ranged from no expected cases, assuming that the
      entire population boiled milk before consumption, to a maximum of 980,128 cases,
      assuming that the entire population drank raw milk without boiling, in the worst
      milk storage conditions, and with the lowest dose-response model. The findings of
      this study clearly show how consumer behavior could affect the probability and
      number of salmonellosis cases and in general, the risk of illness. Hence, the
      proposed RA models emphasize yet again that boiling milk before drinking is a
      simple yet effective tool to protect consumers against the risk of illness
      inherent in the consumption of raw milk. The models may also offer risk managers
      a useful tool to identify or implement appropriate measures to control the risk
      of acquiring foodborne pathogens. Quantification of the risks associated with raw
      milk consumption is necessary from a public health perspective. 

PMID- 25581174
TI  - Storage stability and antibacterial activity of eugenol nanoliposomes prepared by
      an ethanol injection-dynamic high-pressure microfluidization method.
AB  - Eugenol is a major phenolic component with diverse biological activities.
      However, it is difficult to formulate into an aqueous solution due to poor water
      solubility, and this limits its application. In the present study, eugenol
      nanoliposomes (EN) were prepared by combining the ethanol injection method with
      the dynamic high-pressure microfluidization method. Good physicochemical
      characterizations of EN were obtained. The successful encapsulation of eugenol in
      nanoliposomes was confirmed by Fourier transform infrared spectroscopy. A good
      storage stability of EN was confirmed by its low variation of average particle
      diameter and encapsulation efficiency after 8 weeks of storage. No oil drops were
      found in EN after 8 weeks of storage at 4 degrees C and at room temperature,
      which suggested that the poor water solubility of eugenol was overcome by
      nanoliposome encapsulation. Compared with that of eugenol solution, a relatively
      good sustained release property was observed in EN. The antibacterial activity of
      EN against four common foodborne pathogenic bacteria (Staphylococcus aureus,
      Escherichia coli, Salmonella enterica serovar Typhimurium, and Listeria
      monocytogenes) was evaluated in both Luria broth and milk medium. 

PMID- 25581175
TI  - Expression of stress and virulence genes in Escherichia coli O157:H7 heat shocked
      in fresh dairy compost.
AB  - The purpose of this study was to determine the gene expression of Escherichia
      coli O157:H7 heat shocked in dairy compost. A two-step real-time PCR assay was
      used to evaluate the expression of stress and virulence genes in E. coli O157:H7
      heat shocked in compost at 47.5 degrees C for 10 min. Heat-shocked E. coli
      O157:H7 in compost was isolated by using an immunomagnetic bead separation
      method, followed by total RNA extraction, which was then converted to cDNA by
      using a commercial kit. E. coli O157:H7 heat shocked in broth served as the media
      control. In compost, heat shock genes (clpB, dnaK, and groEL) and the alternative
      sigma factor (rpoH) of E. coli O157:H7 were upregulated (P < 0.05), whereas the
      expression of trehalose synthesis genes did not change. Virulence genes, such as
      stx1 and fliC, were upregulated, while genes stx2, eaeA, and hlyA were
      downregulated. In the toxin-antitoxin (TA) system, toxin genes, mazF, hipA, and
      yafQ were upregulated, whereas among antitoxin genes, only dinJ was upregulated
      (P < 0.05). In tryptic soy broth, all heat shock genes (rpoH, clpB, dnaK, and
      groEL) were upregulated (P < 0.05), and most virulence genes (stx1, stx2, hlyA,
      and fliC) and TA genes (mazF-mazE, hipA-hipB, and yafQ-dinJ and toxin gene chpS)
      were down-regulated. Our results revealed various gene expression patterns when
      E. coli O157:H7 inoculated in compost was exposed to a sublethal temperature.
      Clearly, induction of the heat shock response is one of the important protective
      mechanisms that prolongs the survival of pathogens during the composting process.
      In addition, other possible mechanisms (such as the TA system) operating along
      with heat shock response may be responsible for the extended survival of
      pathogens in compost. 

PMID- 25581176
TI  - Survival or growth of inoculated Escherichia coli O157:H7 and Salmonella on
      yellow onions (Allium cepa) under conditions simulating food service and consumer
      handling and storage.
AB  - Whole and diced yellow onions (Allium cepa) were inoculated with five-strain
      cocktails of rifampin-resistant Escherichia coli O157:H7 or Salmonella and stored
      under conditions to simulate food service or consumer handling. The inoculum was
      grown in broth (for both whole and diced onion experiments) or on agar plates
      (for whole onion experiments). Marked circles (3.3 cm in diameter) on the outer
      papery skin of whole onions were spot inoculated (10 MUl in 10 drops) at 7 log
      CFU per circle, and onions were stored at 4 degrees C, 30 to 50 % relative
      humidity, or at ambient conditions (23 degrees C, 30 to 50 % relative humidity).
      Diced onions were inoculated at 3 log CFU/g and then stored in open or closed
      containers at 4 degrees C or ambient conditions. Previously inoculated and
      ambient-stored diced onions were also mixed 1:9 (wt/wt) with refrigerated
      uninoculated freshly diced onions and stored in closed containers at ambient
      conditions. Inoculated pathogens were recovered in 0.1 % peptone and plated onto
      selective and nonselective media supplemented with 50 MUg/ml rifampin. Both E.
      coli O157:H7 and Salmonella populations declined more rapidly on onion skins when
      the inoculum was prepared in broth rather than on agar. Agar-prepared E. coli
      O157:H7 and Salmonella declined by 0.4 and 0.3 log CFU per sample per day,
      respectively, at ambient conditions; at 4 degrees C the rates of reduction were
      0.08 and 0.06 log CFU per sample per day for E. coli O157:H7 and Salmonella,
      respectively. Populations of E. coli O157:H7 and Salmonella did not change over 6
      days of storage at 4 degrees C in diced onions. Lag times of 6 to 9 h were
      observed with freshly inoculated onion at ambient conditions; no lag was observed
      when previously inoculated and uninoculated onions were mixed. Growth rates at
      ambient conditions were 0.2 to 0.3 log CFU/g/h for E. coli O157:H7 and Salmonella
      in freshly inoculated onion and 0.2 log CFU/g/h in mixed product. Diced onions
      support pathogen growth and should be kept refrigerated. 

PMID- 25581177
TI  - Effect of overhead spray and brush roller treatment on the survival of
      Pectobacterium and Salmonella on tomato surfaces.
AB  - Overhead spray and brush roller (OSBR) treatment has been shown to remove
      significantly more Salmonella from tomato surfaces than flume treatment. However,
      OSBR is not widely used in tomato packing facilities compared with other
      commodities, and little is known about whether brushing causes microabrasions or
      other physical damage. Bacteria such as Pectobacterium, a soft rot-producing
      plant pathogen, and Salmonella, a human pathogen, show increased survival and
      growth on damaged tomato surfaces. This study evaluated whether OSBR treatment
      had a negative effect on the safety and/or marketability of tomatoes by examining
      its effect on Pectobacterium and Salmonella survival. Pectobacterium survival was
      evaluated on inoculated tomatoes that were OSBR treated with water or sanitizer
      (100 ppm of NaOCl, 5 ppm of ClO2, or 80 ppm of peracetic acid). A 15-s OSBR
      treatment using water or sanitizer achieved a 3-log CFU/ml reduction in
      Pectobacterium levels. Survival of Pectobacterium and Salmonella on OSBR-treated,
      untreated, and puncture-wounded tomatoes stored at 25 degrees C and 75 to 85 %
      relative humidity for 7 days was also assessed. Both Pectobacterium and
      Salmonella populations declined rapidly on OSBR-treated and untreated tomatoes,
      indicating that brushing does not damage tomato fruit to the extent of promoting
      better pathogen survival. In contrast, the survival of both organisms was
      significantly (P <= 0.05) higher on artificially wounded fruit. These results
      indicate that OSBR treatment does not increase the survival and growth of
      Pectobacterium or Salmonella on tomato surfaces and that it is effective in
      reducing Pectobacterium levels on the surface of inoculated tomatoes. These
      results suggest that, if used properly, an OSBR system in packinghouses is
      effective in removing surface contamination and does not affect tomato quality or
      safety. 

PMID- 25581178
TI  - Contamination of tomatoes with coliforms and Escherichia coli on farms and in
      markets of northwest Nigeria.
AB  - Although recent reports indicated that produce contamination with foodborne
      pathogens is widespread in Nigeria, the sources and magnitude of microbial
      contamination of fruits and vegetables on farms and in markets have not been
      thoroughly identified. To ascertain possible pathways of contamination, the
      frequency and magnitude of coliform and Escherichia coli contamination of
      tomatoes produced in northwest Nigeria was assessed on farms and in markets.
      Eight hundred twenty-six tomato fruit samples and 36 irrigation water samples
      were collected and assessed for fecal indicator organisms. In addition, the
      awareness and use of food safety practices by tomato farmers and marketers were
      determined. Median concentration of coliforms on all field- and market-sourced
      tomato fruit samples, as well as in irrigation water sources, in Kaduna, Kano,
      and Katsina states exceeded 1,000 most probable number (MPN) per g. Median E.
      coli counts from 73 (17%) of 420 field samples and 231 (57%) of 406 market tomato
      fruit samples exceeded 100 MPN/g. Median E. coli concentrations on tomato fruits
      were higher (P < 0.01) in the rainy season (2.45 Log MPN/g), when irrigation was
      not practiced than in the dry (1.10 Log MPN/g) and early dry (0.92 Log MPN/g)
      seasons. Eighteen (50%) of 36 irrigation water samples had E. coli counts higher
      than 126 MPN/100 ml. Median E. coli contamination on market tomato fruit samples
      (2.66 Log MPN/g) were higher (P < 0.001) than those from tomatoes collected on
      farms (0.92 Log MPN/g). Farmers and marketers were generally unaware of the
      relationship between food safety practices and microbial contamination on fresh
      produce. Good agricultural practices pertaining to food safety on farms and in
      local markets were seldom used. Adoption of food safety practices on-farm, during
      transport, and during marketing could improve the microbial quality of tomatoes
      available to the public in this region of the world. 

PMID- 25581179
TI  - Prevalence, antibiogram, and cdt genes of toxigenic Campylobacter jejuni in salad
      style vegetables (ulam) at farms and retail outlets in Terengganu.
AB  - The present study was conducted to investigate the prevalence and antibiotic
      resistance among Campylobacter jejuni in ulam at farms and retail outlets located
      in Kuala Terengganu, Malaysia. A total of 526 samples (ulam, soil, and
      fertilizer) were investigated for the presence of C. jejuni and the gene for
      cytolethal distending toxin (cdt) by using a multiplex PCR method. Antibiotic
      susceptibility to 10 types of antibiotics was determined using the disk diffusion
      method for 33 C. jejuni isolates. The average prevalence of contaminated samples
      from farms, wet markets, and supermarkets was 35.29, 52.66, and 69.88%,
      respectively. The cdt gene was not detected in 24 of the 33 C. jejuni isolates,
      but 9 isolates harbored cdtC. Antibiotic resistance in C. jejuni isolates was
      highest to penicillin G (96.97% of isolates) followed by vancomycin (87.88%),
      ampicillin (75.76%), erythromycin (60.61%), tetracycline (9.09%), amikacin
      (6.06%), and norfloxacin (3.03%); none of the isolates were resistant to
      ciprofloxacin, enrofloxacin, and gentamicin. In this study, C. jejuni was present
      in ulam, and some isolates were highly resistant to some antibiotics but not to
      quinolones. Thus, appropriate attention and measures are required to prevent C.
      jejuni contamination on farms and at retail outlets. 

PMID- 25581180
TI  - Antimicrobial-resistant and extended-spectrum beta-lactamase-producing
      Escherichia coli in raw cow's milk.
AB  - The occurrence of antimicrobial-resistant bacteria is an important public health
      issue. The aim of this study was the monitoring of resistant Escherichia coli in
      raw cow's milk with a focus on the detection of extended-spectrum beta-lactamase
      (ESBL)-producing strains. In total, 263 samples of raw milk from 40 farms were
      collected and investigated in 2010 to 2013 in the Czech Republic. Detection of E.
      coli was performed and evaluated according to ISO 16649-2, and antibiotic
      resistance was screened by the disk diffusion method. The presence of E. coli was
      detected in 243 (92.4%) samples. In total, 270 isolates were obtained. Resistance
      to beta-lactam (31.8%) and tetracycline (13.0%) antibiotics was detected most
      often and also multiresistant strains (5.5%) were observed. E. coli isolates
      found to be resistant to beta-lactam, tetracycline, and quinolone antibiotics
      were assayed by PCR to detect selected genes encoding those resistance
      mechanisms. In isolates in which any bla genes were detected, a double-disk
      synergy test was performed. ESBL production was confirmed in 2 (0.7%) isolates.
      The genetic analysis identified the presence of the blaCTX-M gene and other
      resistance genes (tet(B) and qnrB). Both ESBL-positive isolates originated from
      the same farm and had an identical pulsed-field gel electrophoresis profile. The
      findings of our study indicate that milk can be a reservoir of bacteria carrying
      resistance genes with a potential for spreading through the food chain. 

PMID- 25581181
TI  - Isolation and molecular characterization of multidrug-resistant
      Enterobacteriaceae strains from pork and environmental samples in Xiamen, China.
AB  - This study was conducted to investigate the prevalence and molecular
      characterization of multidrug-resistant (MDR) Enterobacteriaceae isolated from
      swine meat and the breeding environment. A total of 102 MDR Enterobacteriaceae
      strains belonging to five genera were obtained from 210 samples collected from a
      large-scale swine farm from March 2012 to June 2013 in Xiamen, People's Republic
      of China. Among these MDR isolates, Escherichia coli strains were found most
      frequently in both meat and environmental samples, followed by Citrobacter spp.,
      Klebsiella spp., and Shigella spp. The neighbor-joining phylogenetic tree
      indicated that 70.3 % of Escherichia and 50 % of Citrobacter isolates from meat
      samples shared 100 % homology with relevant isolates from environmental samples.
      Resistance was most frequently observed to sulfonamide, trimethoprim,
      aminoglycoside, chloramphenicol, beta-lactam, and tetracycline. Close correlation
      was noted between antibiotic resistance phenotype and the genes responsible for
      resistance to sulfonamide (sulI), trimethoprim (dhfrI), aminoglycoside (aadA,
      aac(3)-I, aphA-1, and aac(3)-IV), chloramphenicol (catI and cmlA), beta-lactam
      (blaSHV, blaOXA, and blaTEM), florfenicol (floR), and tetracycline (tet(A) and
      tet(B)), which were widely distributed with prevalences of 72.5, 6.9, 62.7, 14.7,
      78.4, 11.8, 25.5, 42.2, 12.7, 14.7, 39.2, 87.2, 68.6, and 34.3 % , respectively.
      Class 1 integrons carrying aadA22, dfrA17-aadA5, or dfrA12-aadA2 cassette arrays
      were commonly found in isolates from all samples. The gene cassette aac(6')-Ib-cr
      arr-3-dfrA27-aadA16 was first found in an Enterobacter amnigenus isolate.
      Conjugation experiments revealed the plasmid-mediated transfer of class 1
      integrons. Our results indicate that swine meat and the farming environment can
      be sources of antibiotic-resistant bacteria, which could be potentially
      transmitted to humans via the meat products industry chain. 

PMID- 25581182
TI  - Prevalence of Escherichia coli O157:H7 and Salmonella in camels, cattle, goats,
      and sheep harvested for meat in Riyadh.
AB  - Escherichia coli O157:H7 and Salmonella are significant foodborne pathogens that
      can be found in the feces and on the hides of meat animals. When hides are
      removed during the harvest process, the carcass and subsequent meat products can
      become contaminated. Camels, cattle, sheep, and goats are harvested for meat in
      Riyadh, Saudi Arabia. The prevalence of E. coli O157:H7 and Salmonella are
      unknown in these animals, and it is assumed that if the animals carry the
      pathogens in their feces or on their hides, meat products are likely to become
      contaminated. To this end, a minimum of 206 samples each from hides and feces of
      camels, cattle, goats, and sheep were collected over the course of 8 months and
      tested for E. coli O157:H7 and Salmonella. It was found that E. coli O157:H7 was
      present in feces (10.7, 1.4, 2.4, and 2.4%) and on hides (17.9, 8.2, 2.9, and
      9.2%) of cattle, goats, camels, and sheep, respectively. The prevalence of
      Salmonella was 11.2, 13.5, 23.2, and 18.8% in feces and 80.2, 51.2 67.6, and
      60.2% on hides of cattle, goats, camels, and sheep, respectively. The prevalence
      of E coli O157:H7 was nearly zero in all samples collected in June and July,
      while Salmonella did not exhibit any seasonal variation. These results constitute
      the first comprehensive study of E. coli O157:H7 and Salmonella prevalence in
      Saudi Arabian meat animals at harvest. 

PMID- 25581183
TI  - Bacteriophage cocktail for biocontrol of Salmonella in dried pet food.
AB  - Human salmonellosis has been associated with contaminated pet foods and treats.
      Therefore, there is interest in identifying novel approaches for reducing the
      risk of Salmonella contamination within pet food manufacturing environments. The
      use of lytic bacteriophages shows promise as a safe and effective way to mitigate
      Salmonella contamination in various food products. Bacteriophages are safe,
      natural, highly targeted antibacterial agents that specifically kill bacteria and
      can be targeted to kill food pathogens without affecting other microbiota. In
      this study, we show that a cocktail containing six bacteriophages had a
      broadspectrum activity in vitro against a library of 930 Salmonella enterica
      strains representing 44 known serovars. The cocktail was effective against 95% of
      the strains in this tested library. In liquid culture dose-ranging experiments,
      bacteriophage cocktail concentrations of >=10(8) PFU/ml inactivated more than 90%
      of the Salmonella population (10(1) to 10(3) CFU/ml). Dried pet food inoculated
      with a mixture containing equal proportions of Salmonella serovars Enteritidis
      (ATCC 4931), Montevideo (ATCC 8387), Senftenberg (ATCC 8400), and Typhimurium
      (ATCC 13311) and then surface treated with the six-bacteriophage cocktail (>=2.5
      +/- 1.5 * 10(6) PFU/g) achieved a greater than 1-log (P < 0.001) reduction
      compared with the phosphate-buffered saline-treated control in measured viable
      Salmonella within 60 min. Moreover, this bacteriophage cocktail reduced natural
      contamination in samples taken from an undistributed lot of commercial dried dog
      food that tested positive for Salmonella. Our results indicate that bacteriophage
      biocontrol of S. enterica in dried pet food is technically feasible. 

PMID- 25581184
TI  - Comparison of desiccation tolerance among Listeria monocytogenes, Escherichia
      coli O157:H7, Salmonella enterica, and Cronobacter sakazakii in powdered infant
      formula.
AB  - Bacterial pathogens such as Listeria monocytogenes, Escherichia coli O157:H7,
      Salmonella enterica, and Cronobacter sakazakii have demonstrated long-term
      survival in/on dry or low-water activity (aw) foods. However, there have been few
      comparative studies on the desiccation tolerance among these bacterial pathogens
      separately in a same food matrix. In the present study, the survival kinetics of
      the four bacterial pathogens separately inoculated onto powdered infant formula
      as a model low-aw food was compared during storage at 5, 22, and 35 degrees C. No
      significant differences in the survival kinetics between E. coli O157:H7 and L.
      monocytogenes were observed. Salmonella showed significantly higher desiccation
      tolerance than these pathogens, and C. sakazakii demonstrated significantly
      higher desiccation tolerance than all other three bacteria studied. Thus, the
      desiccation tolerance was represented as C. sakazakii > Salmonella > E. coli
      O157:H7 = L. monocytogenes. The survival kinetics of each bacterium was
      mathematically analyzed, and the observed kinetics was successfully described
      using the Weibull model. To evaluate the variability of the inactivation kinetics
      of the tested bacterial pathogens, the Monte Carlo simulation was performed using
      assumed probability distribution of the estimated fitted parameters. The
      simulation results showed that the storage temperature significantly influenced
      survival of each bacterium under the dry environment, where the bacterial
      inactivation became faster with increasing storage temperature. Furthermore, the
      fitted rate and shape parameters of the Weibull model were successfully modelled
      as a function of temperature. The numerical simulation of the bacterial
      inactivation was realized using the functions of the parameters under arbitrary
      fluctuating temperature conditions. 

PMID- 25581185
TI  - Variation in heat and pressure resistance of verotoxigenic and nontoxigenic
      Escherichia coli.
AB  - This study evaluated the heat and pressure resistance of 112 strains of
      Escherichia coli, including 102 strains of verotoxigenic E. coli (VTEC)
      representing 23 serotypes and four phylogenetic groups. In an initial screening,
      the heat and pressure resistance of 100 strains, including 94 VTEC strains, were
      tested in phosphate-buffered saline (PBS). Treatment at 60 degrees C for 5 min
      reduced cell counts by 2.0 to 5.5 log CFU/ml; treatment at 600 MPa for 3 min at
      25 degrees C reduced the cell counts by 1.1 to 5.5 log CFU/ml. Heat or pressure
      resistance did not correlate to the phylogenetic group or the serotype. A smaller
      group of E. coli strains was evaluated for heat and pressure resistance in Luria
      Bertani (LB) broth. Generally, the levels of heat resistance of E. coli strains
      in LB and PBS were similar; however, the levels of pressure resistance observed
      for treatments in LB broth or PBS were variable. The cell counts of pressure
      resistant strains of VTEC were reduced by less than 1.5 log CFU/ml after
      treatment at 600 MPa for 3 min. E. coli strains were also treated with 600 MPa
      for 3 min in ground beef or inoculated into beef patties and grilled to 63 or 71
      degrees C. The cell counts of the VTEC E. coli O26:H11 strain 05-6544 were
      reduced by 2 log CFU/g by pressure treatment in ground beef. The cell counts of
      the heat-resistant E. coli strain AW1.7 were reduced by 1.4 and 3.4 log CFU/g in
      beef patties grilled to internal temperatures of 63 and 71 degrees C,
      respectively. The cell counts of E. coli 05-6544 were reduced by less than 3 and
      6 log CFU/g in beef patties grilled to internal temperatures of 63 and 71 degrees
      C, respectively. To study whether the composition of the beef patties influenced
      heat resistance, E. coli strains AW1.7, AW1.7 Delta pHR1, MG1655, and LMM1030
      were mixed into beef patties containing 15 or 35% fat and 0 or 2% NaCl, and the
      patties were grilled to an internal temperature of 63 degrees C. The highest heat
      resistance of E. coli was observed in patties containing 15% fat and 2% NaCl. 

PMID- 25581186
TI  - Effects of environmental parameters on the dual-species biofilms formed by
      Escherichia coli O157:H7 and Ralstonia insidiosa, a strong biofilm producer
      isolated from a fresh-cut produce processing plant.
AB  - Biofilm-forming bacteria resident to food processing facilities are a food safety
      concern due to the potential of biofilms to harbor foodborne bacterial pathogens.
      When cultured together, Ralstonia insidiosa, a strong biofilm former frequently
      isolated from produce processing environments, has been shown to promote the
      incorporation of Escherichia coli O157:H7 into dual-species biofilms. In this
      study, interactions between E. coli O157:H7 and R. insidiosa were examined under
      different incubating conditions. Under static culture conditions, the
      incorporation of E. coli O157:H7 into biofilms with R. insidiosa was not
      significantly affected by either low incubating temperature (10 degrees C) or by
      limited nutrient availability. Greater enhancement of E. coli O157:H7
      incorporation in dual-species biofilms was observed by using a continuous culture
      system with limited nutrient availability. Under the continuous culture
      conditions used in this study, E coli O157:H7 cells showed a strong tendency of
      colocalizing with R. insidiosa on a glass surface at the early stage of biofilm
      formation. As the biofilms matured, E coli O157:H7 cells were mostly found at the
      bottom layer of the dual-species biofilms, suggesting an effective protection by
      R. insidiosa in the mature biofilms. 

PMID- 25581187
TI  - Tannin-rich pomegranate rind extracts reduce adhesion to and invasion of Caco-2
      Cells by Listeria monocytogenes and decrease its expression of virulence genes.
AB  - Pomegranate rind is rich in tannins that have remarkable antimicrobial
      activities. This study aimed to evaluate the effects of a tannin-rich fraction
      from pomegranate rind (TFPR) on Listeria monocytogenes virulence gene expression
      and on the pathogen's interaction with human epithelial cells. Growth curves were
      monitored to determine the effect of TFPR on L. monocytogenes growth. The 3-(4,5
      dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide and fluorescence staining
      assays were used to examine the cytotoxicity of TFPR. The effects of TFPR on L.
      monocytogenes adhesion to and invasion of epithelial cells were investigated
      using Caco-2 cells. Real-time quantitative PCR analysis was conducted to quantify
      mRNA levels of three virulence genes in L. monocytogenes. Results showed that a
      MIC of TFPR against L. monocytogenes was 5 mg/ml in this study. TFPR exhibited
      cytotoxicity against Caco-2 cells when the concentration was 2.5 mg/ml.
      Subinhibitory concentrations of TFPR significantly reduced, in a dose-dependent
      manner, adhesion to and invasion of Caco-2 cells by L. monocytogenes. When L.
      monocytogenes was grown in the presence of 2.5 mg/ml TFPR, the transcriptional
      levels of prfA, inlA, and hly decreased by 17-, 34-, and 28-fold, respectively. 

PMID- 25581188
TI  - Listeria monocytogenes in Retail Delicatessens: an Interagency Risk Assessment
      model and baseline results.
AB  - The Interagency Risk Assessment-Listeria monocytogenes (Lm) in Retail
      Delicatessens provides a scientific assessment of the risk of listeriosis
      associated with the consumption of ready-to-eat (RTE) foods commonly prepared and
      sold in the delicatessen (deli) of a retail food store. The quantitative risk
      assessment (QRA) model simulates the behavior of retail employees in a deli
      department and tracks the Lm potentially present in this environment and in the
      food. Bacterial growth, bacterial inactivation (following washing and sanitizing
      actions), and cross-contamination (from object to object, from food to object, or
      from object to food) are evaluated through a discrete event modeling approach.
      The QRA evaluates the risk per serving of deli-prepared RTE food for the
      susceptible and general population, using a dose-response model from the
      literature. This QRA considers six separate retail baseline conditions and
      provides information on the predicted risk of listeriosis for each. Among the
      baseline conditions considered, the model predicts that (i) retail delis without
      an environmental source of Lm (such as niches), retail delis without niches that
      do apply temperature control, and retail delis with niches that do apply
      temperature control lead to lower predicted risk of listeriosis relative to
      retail delis with niches and (ii) retail delis with incoming RTE foods that are
      contaminated with Lm lead to higher predicted risk of listeriosis, directly or
      through cross-contamination, whether the contaminated incoming product supports
      growth or not. The risk assessment predicts that listeriosis cases associated
      with retail delicatessens result from a sequence of key events: (i) the
      contaminated RTE food supports Lm growth; (ii) improper retail and/or consumer
      storage temperature or handling results in the growth of Lm on the RTE food; and
      (iii) the consumer of this RTE food is susceptible to listeriosis. The risk
      assessment model, therefore, predicts that cross-contamination with Lm at retail
      predominantly results in sporadic cases. 

PMID- 25581189
TI  - Effect of sporulation temperature on the resistance of Clostridium botulinum type
      A spores to thermal and high pressure processing.
AB  - The purpose of this study was to determine the effect of sporulation temperature
      on the resistance of Clostridium botulinum type A spores of strains 62A and
      GiorgioA to thermal and high pressure processing (HPP). Spore crops produced in
      Trypticase-peptone-glucose-yeast extract broth at four incubation temperatures
      (20, 27, 37, and 41 degrees C) were harvested, and heat resistance studies were
      conducted at 105 degrees C (strain 62A) and 100 degrees C (strain GiorgioA).
      Resistance to HPP was evaluated by subjecting the spores to a high pressure (700
      MPa) and temperature combination (105 degrees C, strain 62A; 100 degrees C strain
      GiorgioA) in a laboratory-scale pressure test system. The decimal reduction time
      (D-value) was calculated using the log-linear model. Although the time to
      sporulation for GiorgioA was shorter and resulted in higher spore concentrations
      than for 62A at 20, 27, and 37 degrees C, GiorgioA did not produce a sufficient
      spore crop at 41 degrees C to be evaluated. The heat resistance of 62A spores was
      greatest when produced at 27 degrees C and decreased for spore crops produced
      above or below 27 degrees C (D105 degrees C-values: 20 degrees C, 1.9 min; 27
      degrees C, 4.03 min; 37 degrees C, 3.66 min; and 41 degrees C, 3.5 min; P <
      0.05). Unlike 62A, the heat resistance behavior of GiorgioA spores increased with
      rising sporulation temperature, and spores formed at the organism's optimum
      growth temperature of 37 degrees C were the most resistant (D100 degrees C
      values: 20 degrees C, 3.4 min; 27 degrees C, 5.08 min; and 37 degrees C, 5.65
      min; P < 0.05). Overall, all spore crops were less resistant to pressure-assisted
      thermal processing than thermal treatment alone. Sporulation temperature has an
      effect on the resistance of C. botulinum spores to heat and HPP, and is
      characteristic to a particular strain. Knowledge of the effect of sporulation
      temperature on the resistance of C. botulinum spores is vital for the production
      of spores utilized in thermal and high pressure inactivation studies.

PMID- 25581190
TI  - Flumethrin residue levels in honey from apiaries of China by high-performance
      liquid chromatography.
AB  - A method for detection of flumethrin residue in honey by high-performance liquid
      chromatography was established. After n-hexane-dichloromethane (4:6, vol/vol)
      extraction, the honey samples were concentrated by rotary evaporation, purified
      by an Oasis HLB solid-phase extraction column, and detected using a UV detector
      at 267 nm. The interference of the matrix was greatly reduced by optimizing
      pretreatment conditions; thus, the minimal detection limit of cyhalothrin was
      0.005 mg/kg, the average recovery was 80.8 to 96.8%, and the coefficient of
      variation was 0.6 to 1.5%. The precision and reproducibility of this method was
      suitable and applicable for detecting flumethrin residue in honey. With this
      method, 135 honey samples from seven locations in the People's Republic of China
      were tested; 77 samples tested positive for flumethrin residue, resulting in a
      detection rate of 75.3%. Samples from the Guangdong province had the highest
      flumethrin residue level (0.122 mg/kg) of the locations tested. On the basis of
      analytical validation, the high-performance liquid chromatography has been shown
      to be a promising alternative for the analysis of flumethrin residue in honey
      samples. 

PMID- 25581191
TI  - Effect of the yeast Rhodosporidium paludigenum on postharvest decay and patulin
      accumulation in apples and pears.
AB  - The effect of a strain of marine yeast Rhodosporidium paludigenum on postharvest
      blue mold and patulin accumulation in apples and pears stored at 23 degrees C was
      evaluated. The occurrence and severity of apple and pear decay caused by
      Penicillium expansum were significantly inhibited by R. paludigenum. However, the
      application of the yeast at a high concentration (10(8) cells per ml) enhanced
      patulin accumulation after 7 days of storage; the amount of patulin increased
      24.2 times and 12.6 times compared to the controls in infected apples and pears,
      respectively. However, R. paludigenum reduced the patulin concentration in the
      growth medium by both biological degradation and physical adsorption. Optimal in
      vitro patulin reduction was observed at 30 degrees C and at pH 6.0. R.
      paludigenum incubated at 28 degrees C was tolerant to patulin at concentrations
      up to 100 mg/liter. In conclusion, R. paludigenum was able to control postharvest
      decay in apples and pears and to remove patulin in vitro effectively. However,
      because the yeast induced patulin accumulation in fruit, the assessment of
      mycotoxin content after biological treatments in postharvest decay control is
      important. R. paludigenum may also be a promising source of gene(s) and enzyme(s)
      for patulin degradation and may be a tool to decrease patulin contamination in
      commercial fruit-derived products. 

PMID- 25581192
TI  - Changes in the microbiological quality of mangrove oysters (Crassostrea
      brasiliana) during different storage conditions.
AB  - This study aimed to determine the effect of temperature and period of postharvest
      storage on the microbiological quality and shelf life of raw mangrove oysters,
      Crassostrea brasiliana. A total of 150 dozen oysters were collected directly from
      the points of extraction or cultivation in southern Brazil, and in the
      laboratory, they were stored raw at 5, 10, 15, 20, and 25 degrees C for 1, 4, 8,
      11, and 15 days. On each of these days, the oysters were subjected to
      microbiological analyses of aerobic mesophilic count, total coliforms,
      enterococci, Escherichia coli, Staphylococcus aureus, and Salmonella. None of the
      tested samples under any storage condition showed contamination levels above
      those allowed by Brazilian legislation for E. coli, S. aureus, and Salmonella,
      and there was no change (P > 0.05) in the counts of these microorganisms due to
      the temperature and/or period of oyster storage. Counts of enterococci and total
      coliforms showed a tendency to increase (P < 0.05) among the different
      temperatures tested. Raw mangrove oysters remain in safe microbiological
      conditions for consumption up to 8 days after harvesting, regardless of
      temperature, and their shelf life may be extended to 15 days if they are stored
      at temperatures not exceeding 15 degrees C. 

PMID- 25581193
TI  - Effect of supercritical fluid extraction on the reduction of toxic elements in
      fish oil compared with other extraction methods.
AB  - High-quality fish oil for human consumption requires low levels of toxic
      elements. The aim of this study was to compare different oil extraction methods
      to identify the most efficient method for extracting fish oil of high quality
      with the least contamination. The methods used in this study were Soxhlet
      extraction, enzymatic extraction, wet reduction, and supercritical fluid
      extraction. The results showed that toxic elements in fish oil could be reduced
      using supercritical CO2 at a modest temperature (60 degrees C) and pressure (35
      MPa) with little reduction in the oil yield. There were significant reductions in
      mercury (85 to 100%), cadmium (97 to 100%), and lead (100%) content of the fish
      oil extracted using the supercritical fluid extraction method. The fish oil
      extracted using conventional methods contained toxic elements at levels much
      higher than the accepted limits of 0.1 MUg/g. 

PMID- 25581194
TI  - Consumer-reported handling of raw poultry products at home: results from a
      national survey.
AB  - Salmonella and Campylobacter cause an estimated combined total of 1.8 million
      foodborne infections each year in the United States. Most cases of salmonellosis
      and campylobacteriosis are associated with eating raw or undercooked poultry or
      with cross-contamination. Between 1998 and 2008, 20% of Salmonella and 16% of
      Campylobacter foodborne disease outbreaks were associated with food prepared
      inside the home. A nationally representative Web survey of U.S. adult grocery
      shoppers (n = 1,504) was conducted to estimate the percentage of consumers who
      follow recommended food safety practices when handling raw poultry at home. The
      survey results identified areas of low adherence to current recommended food
      safety practices: not washing raw poultry before cooking, proper refrigerator
      storage of raw poultry, use of a food thermometer to determine doneness, and
      proper thawing of raw poultry in cold water. Nearly 70% of consumers reported
      washing or rinsing raw poultry before cooking it, a potentially unsafe practice
      because "splashing" of contaminated water may lead to the transfer of pathogens
      to other foods and other kitchen surfaces. Only 17.5% of consumers reported
      correctly storing raw poultry in the refrigerator. Sixty-two percent of consumers
      own a food thermometer, and of these, 26% or fewer reported using one to check
      the internal temperature of smaller cuts of poultry and ground poultry. Only 11%
      of consumers who thaw raw poultry in cold water reported doing so correctly. The
      study results, coupled with other research findings, will inform the development
      of science-based consumer education materials that can help reduce foodborne
      illness from Salmonella and Campylobacter. 

PMID- 25581195
TI  - Managerial practices regarding workers working while ill.
AB  - Surveillance data indicate that handling of food by an ill worker is a cause of
      almost half of all restaurant-related outbreaks. The U.S. Food and Drug
      Administration (FDA) Food Code contains recommendations for food service
      establishments, including restaurants, aimed at reducing the frequency with which
      food workers work while ill. However, few data exist on the extent to which
      restaurants have implemented FDA recommendations. The Centers for Disease Control
      and Prevention's Environmental Health Specialists Network (EHS-Net) conducted a
      study on the topic of ill food workers in restaurants. We interviewed restaurant
      managers (n = 426) in nine EHS-Net sites. We found that many restaurant policies
      concerning ill food workers do not follow FDA recommendations. For example, one
      third of the restaurants' policies did not specifically address the circumstances
      under which ill food workers should be excluded from work (i.e., not be allowed
      to work). We also found that, in many restaurants, managers are not actively
      involved in decisions about whether ill food workers should work. Additionally,
      almost 70% of managers said they had worked while ill; 10% said they had worked
      while having nausea or "stomach flu," possible symptoms of foodborne illness.
      When asked why they had worked when ill, a third of the managers said they felt
      obligated to work or their strong work ethic compelled them to work. Other
      reasons cited were that the restaurant was understaffed or no one was available
      to replace them (26%), they felt that their symptoms were mild or not contagious
      (19%), they had special managerial responsibilities that no one else could
      fulfill (11%), there was non-food handling work they could do (7%), and they
      would not get paid if they did not work or the restaurant had no sick leave
      policy (5%). Data from this study can inform future research and help policy
      makers target interventions designed to reduce the frequency with which food
      workers work while ill. 

PMID- 25581196
TI  - Detection of non-O157 Shiga toxin-producing Escherichia coli in 375 grams of beef
      trim enrichments across multiple commercial PCR detection platforms.
AB  - Although serotype O157:H7 remains the pathogenic Shiga toxin-producing
      Escherichia coli (STEC) of primary concern worldwide, some focus in the United
      States has shifted to six particular non-O157 STEC serogroups (O26, O45, O103,
      O111, O121, and O145). Some of these serogroups have also emerged as concerns
      elsewhere around the world, including Europe. The objective of this work was to
      compare commercial detection methods with the U.S. Department of Agriculture
      (USDA) reference method for detection of non-O157 STEC in 375 g of beef trim
      using a limit of detection study design. Overall, the commercial platforms
      performed well, showing similar levels of sensitivity for detection of
      presumptive positives for O45, O26, O103, and O121 (PCR screen results only). For
      O111, one method that utilizes an integrated immunomagnetic separation and PCR
      approach was more sensitive than a PCR-only screen approach. Additionally, one
      commercial method showed more presumptive and confirmed positives overall. Use of
      an immunomagnetic separation tool, such as antibody-coated beads, aided
      considerably with the confirmation procedures and is an important step when
      confirming suspect samples. A secondary goal of this study was to evaluate
      isolation and International Organization for Standardization confirmation
      protocols used in Europe compared with strategies provided by the USDA
      Microbiology Laboratory Guidebook (MLG). Generally, results from the USDA
      confirmation plates (modified Rainbow agar) were better than the European Union
      confirmation plates (MacConkey agar with or without rhamnose). In summary,
      detection of non-O157 STEC in 375 g of beef trim can be performed by any of the
      three methods on the market evaluated in the study. 

PMID- 25581197
TI  - Microbiological survey of locally grown lettuce sold at farmers' markets in
      Vancouver, British Columbia.
AB  - Increased consumer demand for fresh leafy produce has been paralleled by an
      increase in outbreaks and illness associated with these foods. Presently, data on
      the microbiological quality and safety of produce harvested in the Lower Mainland
      of British Columbia is lacking. Therefore, fresh green, red, and romaine lettuce
      samples (n = 68) were obtained from five regional farmers' markets in late summer
      of 2012 and subsequently analyzed to determine total numbers of aerobic bacteria,
      coliforms, and Escherichia coli. Additionally, enrichment procedures were used to
      detect low concentrations of E. coli. Obtained E. coli isolates were subjected to
      multiplex PCRs to determine phylogenetic groupings and the presence of virulence
      genes (eaeA, hlyA, stx1, and stx2). All E. coli were tested for resistance to 15
      antibiotics using a disk diffusion assay. Lettuce samples yielded mean aerobic
      colony counts of 6.3 log CFU/g. Coliforms were detected in 72% of samples, with a
      median concentration of 1.9 log CFU/g. Of samples, 13% were found to harbor E.
      coli, with a median level of 0.7 log CFU/g. Antibiogram typing of all E. coli (n
      = 33) revealed that 97% possessed resistance to one or more antimicrobials, with
      resistance to amikacin (58%), trimethoprim (48%), and trimethoprim
      sulfamethoxazole (45%) being the most common. Phylogroup typing showed that 79%
      of these isolates belonged to group B1, with the remaining assigned to groups A
      (9%) or D (12%); no virulence genes were detected. Considering that phylogroup
      indicators suggestive of fecal contamination (groups A and D E. coli) were
      recovered in lettuce samples presented at retail, further work is required to
      explore at what point along the food chain contamination occurs. Also, this study
      shows the presence of multidrug-resistant E. coli in fresh vegetables. Summed,
      these data provide important information on the microbiological quality of leafy
      vegetables grown in British Columbia through the detection and characterization
      of frequently used indicator organisms. 

PMID- 25581198
TI  - Intracloacal inoculation, an effective screening method for determining the
      efficacy of probiotic bacterial isolates against Campylobacter colonization in
      broiler chickens.
AB  - Campylobacter is a leading cause of foodborne illness worldwide. It is common in
      poultry, and human infections are often associated with consumption of
      contaminated poultry products. One strategy to reduce Campylobacter colonization
      in poultry is the use of oral probiotics, but this produces variable results,
      possibly because the probiotics are destroyed in the stomach's acidic
      environment. Protection (e.g., encapsulation) of isolates may overcome this
      problem, but there is no assurance that these isolates will have efficacy in the
      lower gastrointestinal tract. Therefore, screening candidate isolates by directly
      placing them in the lower intestinal tract via cloacal inoculation may eliminate
      the time and expense of encapsulating ineffective isolates. Thus, the purpose of
      this study was to collect bacterial isolates with anti-Campylobacter activity in
      vitro and evaluate their efficacy in vivo upon either oral or intracloacal
      administration. Bacterial isolates were collected from healthy birds and were
      evaluated for efficacy against C. jejuni in vitro. Isolates having generally
      regarded as safe status and demonstrating in vitro anti-Campylobacter properties
      were evaluated after oral or intracloacal inoculation into chicks on day 1 (n =
      10 birds per isolate per route of administration). On day 7, birds were dosed by
      oral gavage with a four-strain mixture of wild-type Campylobacter containing at
      least 1 * 10(7) CFU/ml organisms. On day 14, birds were euthanized and the ceca
      were collected aseptically for Campylobacter enumeration. When dosed orally, only
      one isolate had a 1-log reduction in cecal Campylobacter counts, whereas when
      administered intracloacally, six of these isolates produced a 1- to 3-log
      reduction in cecal Campylobacter counts in 14-day-old chickens. These results
      support the strategy of evaluating the efficacy of potential probiotic isolates
      via cloacal inoculation prior to undergoing the effort of encapsulating isolates
      for oral administration. 

PMID- 25581199
TI  - Detection of quinolones in commercial eggs obtained from farms in the Espaillat
      Province in the Dominican Republic.
AB  - Previously, we reported the use of quinolones in broiler chickens resulted in
      residues in retail poultry meat obtained from nine districts in the Santiago
      Province of the Dominican Republic. Residues in poultry products are a concern
      due to consumer allergies and the potential to develop antibiotic-resistant
      bacteria. Given the use of quinolones in poultry production and our previous
      findings in poultry meat, the objective of this study was to evaluate the
      presence of quinolone residues in eggs. Samples were collected from 48 different
      farms located in three of the four municipalities (Moca, Cayetano Germosen, and
      Jamao) of the Espaillat Province. Each farm was sampled three times between July
      and September for a total of 144 samples. Samples were evaluated qualitatively
      and quantitatively for quinolone residues using the Equinox test. Operation
      systems (cage or floor), seasonality, and location were considered along with egg
      producer sizes that were defined as small scale, <30,000 eggs per day; medium
      scale, 30,000 to 60,000 eggs per day; or large scale, >60,000 eggs per day. From
      small-, medium-, and large-scale producers, 69, 50, and 40% of samples were
      positive for quinolone residues, respectively. A greater number of samples were
      positive (61%) in floor-laying hen producers compared with those using cages
      (40%). In the Jamao municipality, 67% of the samples were positive compared with
      Moca and Cayetano Germosen, where 56 and 25% of samples were positive,
      respectively. Sampling time had an effect on percent positives: samples collected
      in July, August, and September were 71, 19, and 63% positive, respectively.
      Overall, 51% of the samples obtained from eggs produced in the province of
      Espaillat were positive for quinolone residues at levels higher than the maximum
      limits for edible tissue established by the regulatory agencies, including the
      European Union and U.S. Department of Agriculture. The results obtained from this
      research confirmed the presence of quinolone residue in eggs, which may present a
      health risk to some consumers. 

PMID- 25581200
TI  - Prevalence, toxin gene profiles, and antimicrobial resistance of Staphylococcus
      aureus isolated from quick-frozen dumplings.
AB  - The aim of this study was to investigate the prevalence of Staphylococcus aureus
      in quick-frozen dumplings and to characterize these strains. A total of 120
      dumpling samples, including lamb (n = 13), vegetarian (n = 14), seafood (n = 12),
      and pork (n = 81) stuffing, were collected in Shaanxi province in China and
      screened for S. aureus. All S. aureus isolates were characterized by
      antimicrobial susceptibility testing, and detection of genes encoding
      staphylococcal enterotoxins, exfoliative toxins A and B (eta and etb), toxic
      shock syndrome toxin 1 (tsst-1), and resistance to methicillin-oxacillin (mecA).
      In all, 60.0% of all samples were positive for S. aureus, and 117 S. aureus
      isolates, including seven mecA-positive strains, were recovered from these
      positive samples. In addition, all mecA-positive S. aureus isolates were
      recovered from products of animal origin. In these S. aureus isolates, resistance
      was observed most frequently to ampicillin (92.3%) and penicillin (86.3%),
      followed by clarithromycin, erythromycin, midecamycin, tetracycline, and
      kanahemycin (from 53.8 to 28.2%). All isolates were sensitive to cefoperazone,
      minocycline, vancomycin, and ofloxacin. The predominant toxin gene was sec
      (38.5%), followed by seg (19.7%), sej (16.2%), see (12.8%), sea (11.1%), and seb
      (10.3%), whereas eta, etb, and tsst-1 genes were not detected. These findings
      indicate that S. aureus was present commonly in quick-frozen dumplings,
      accompanied by multiple antimicrobial resistance and toxin genes. Our findings
      highlight the urgency for stricter hygiene strategies in food production and the
      prudent use of antibiotics in the breeding industry. 

PMID- 25581201
TI  - Tenacity of human norovirus and the surrogates feline calicivirus and murine
      norovirus during long-term storage on common nonporous food contact surfaces.
AB  - The transfer of human norovirus (hNV) to food via contaminated surfaces is highly
      probable during food production, processing, and preparation. In this study, the
      tenacity of hNV and its cultivable surrogates feline calicivirus (FCV) and murine
      norovirus (MNV) on two common nonporous surface materials at two storage
      temperatures was directly compared. Virus titer reduction on artificially
      inoculated stainless steel and plastic carriers was monitored for 70 days at room
      temperature and at 7 degrees C. Viruses were recovered at various time points by
      elution. Genomes from intact capsids (hNV, FCV, and MNV) were quantified with
      real-time reverse transcription (RT) PCR, and infectivity (FCV and MNV) was
      assessed with plaque assay. RNase treatment before RNA extraction was used to
      eliminate exposed RNA and to assess capsid integrity. No significant differences
      in titer reduction were found between materials (stainless steel or plastic) with
      the plaque assay or the real-time quantitative RT-PCR. At room temperature,
      infectious FCV and MNV were detected for 7 days. Titers of intact hNV, FCV, and
      MNV capsids dropped gradually and were still detectable after 70 days with a loss
      of 3 to 4 log units. At 7 degrees C, the viruses were considerably more stable
      than they were at room temperature. Although only MNV infectivity was unchanged
      after 70 days, the numbers of intact capsids (hNV, FCV, and MNV) were stable with
      less than a 1-log reduction. The results indicate that hNV persists on food
      contact surfaces and seems to remain infective for weeks. MNV appears to be more
      stable than FCV at 7 degrees C, and thus is the most suitable surrogate for hNV
      under dry conditions. Although a perfect quantitative correlation between intact
      capsids and infective particles was not obtained, real-time quantitative RT-PCR
      provided qualitative data about hNV inactivation characteristics. The results of
      this comparative study might support future efforts in assessment of foodborne
      virus risk and food safety. 

PMID- 25581202
TI  - Quantitative multiplex real-time PCR assay for shrimp allergen: comparison of
      commercial master mixes and PCR platforms in rapid cycling.
AB  - Real-time PCR has been used widely in numerous fields. In food safety, it has
      been applied to detection of microbes and other contaminants, including food
      allergens. Interest in rapid (fast) cycling real-time PCR has grown because it
      yields results in less time than does conventional cycling. However, fast cycling
      can adversely affect assay performance. Here we report on tests of commercial
      master mixes specifically designed for fast real-time PCR using a shrimp allergen
      assay we previously developed and validated. The objective of this work was to
      determine whether specialized commercial master mixes lead to improved assay
      performance in rapid cycling. Real-time PCR assays were carried out using four
      different master mixes and two different rapid cycling protocols. Results
      indicated that specialized master mixes did yield quality results. In many cases,
      linear ranges spanned up to 7 orders of magnitude, R(2) values were at least
      0.95, and reaction efficiencies were within or near the optimal range of 90 to
      110%. In the faster of the two rapid cycling protocols tested, assay performance
      and PCR amplification were markedly better for the shorter PCR product. In
      conclusion, specialized commercial master mixes were effective as part of rapid
      cycling protocols, but conventional cycling as used in our previous work is more
      reliable for the shrimp assay tested. 

PMID- 25581203
TI  - The bilateral central vestibular system: its pathways, functions, and disorders.
AB  - The bilateral anatomical organization of the vestibular system provides three
      functional advantages: optimal differentiation of head motion and orientation,
      sensory substitution of a unilateral peripheral failure, and central compensation
      of a peripheral or central vestibular tone imbalance. The structure is based on
      bilaterally ascending and descending pathways and at least four crossings: three
      in the brain stem and one in the cortex. The resulting sensorimotor functions can
      be subdivided into three major groups: (1) reflexive control of gaze, head, and
      body in three spatial planes (yaw, pitch, roll) at the brain stem/cerebellar
      level; (2) perception of self-motion and control of voluntary movement and
      balance at the cortical/subcortical level; and (3) higher vestibular cognitive
      functions (e.g., spatial memory and navigation). The bilateral representation of
      the vestibular system in multiple multisensory cortical areas and the vestibular
      dominance of the nondominant hemisphere raise the question of how one global
      percept of motion and orientation in space is formed. 

PMID- 25581204
TI  - A single-center strategy to minimize blood transfusion in neonates and children
      undergoing cardiac surgery.
AB  - BACKGROUND: The transfusion of blood products in the setting of uncontrolled
      bleeding is unquestionably lifesaving. However, in many instances, the decision
      to transfuse is based on physician gestalt rather than medical evidence. When
      indications for transfusion are unclear, the benefits of blood products must be
      balanced against their significant risks and associated costs. As our institution
      is a referral center for patients of Jehovah's Witness faith, this population has
      pushed our development of techniques to achieve the goal of bloodless surgery.
      Our practices in caring for this population have become our standard practice for
      managing all patients undergoing congenital cardiac surgery. OBJECTIVES: To
      evaluate our success in minimizing the use of blood products during pediatric
      cardiac surgery. METHODS: After IRB approval, we retrospectively reviewed all
      patients who underwent cardiac surgery utilizing cardiopulmonary bypass (CPB),
      for biventricular repair procedures. The study was conducted at a single
      institution (Nationwide Children's Hospital (NCH)) during the period: January 1,
      2013 and December 31, 2013. RESULTS: A total of 209 patients were included.
      Overall, 81 patients (38.8%) and 81 of 136 (59.6%) weighing more than 6 kg
      received no blood products (bloodless) during their entire hospital stay.
      Bloodless surgery was most successful in patients weighing more than 18 kg,
      followed by patients weighing 6-18 kg. All 73 patients who weighed <6 kg received
      blood transfusion during their hospitalization. CONCLUSION: The techniques that
      we have developed to initially care for our Jehovah's Witness families may be
      applied to other pediatric and adult surgical procedures.

PMID- 25581205
TI  - Multivariable risk of developing new onset diabetes after transplant-results from
      a single-center study of 481 adult, primary kidney transplant recipients.
AB  - BACKGROUND: Understanding the relative contributions of baseline demographics and
      immunosuppressive therapy on NODAT risk may help in developing preventive
      strategies. METHODS: Using our prospectively followed cohort of 481 adult,
      primary kidney transplant recipients without pre-transplant diabetes, we
      determined the significant baseline predictors for the hazard rate of developing
      NODAT via Cox stepwise regression. The multivariable influence of first BPAR
      (defined as a time-dependent covariate) was also tested. RESULTS: Median follow
      up was 57 mo post-transplant; the overall percentage who developed NODAT was
      22.5% (108/481). Four baseline predictors of a greater NODAT hazard rate were
      found (by order of selection): higher BMI (p < 0.000001), planned maintenance
      with SRL (p = 0.0003), non-white recipient (p = 0.0004), and older recipient age
      (p = 0.0004). Approximately one-half of the 106 patients in the highest
      demographic risk category (BMI >=25 kg/m(2) , non-white race, and age at
      transplant >=40 yr) developed NODAT; actuarial NODAT risk ranged from 10% to 30%
      in the lower demographic risk categories. First BPAR was also associated with
      significantly higher NODAT in multivariable analysis (p = 0.02)-the highly
      elevated NODAT rate observed during the first few months post-transplant and
      following first BPAR appears to demonstrate the diabetogenic effect of using high
      dose (intravenous) corticosteroids. CONCLUSIONS: The disturbingly high NODAT rate
      found among patients having multiple demographic risk factors is still an
      important problem that awaits a better solution.

PMID- 25581206
TI  - Prevalence and predictors of distress in posttreatment adult leukemia and
      lymphoma survivors.
AB  - This paper examines predictors of cancer-specific distress among posttreatment
      adult leukemia and lymphoma survivors (LLS). Using a survey mailed to LLS in the
      Colorado Central Cancer Registry (N = 477), the authors developed a multivariable
      risk profile for distress. Thirty one percent of LLS reported indicators of
      distress. Significantly higher distress was associated with younger age (p <
      0.001) in bivariate analyses. The risk profile included fear of recurrence,
      financial burden, and younger age. Distress did not attenuate based on time since
      treatment completion and may persist up to 4 years posttreatment, suggesting a
      need for intervention, particularly among high-risk LLS.

PMID- 25581208
TI  - A comparison of chemiluminescent acridinium dimethylphenyl ester labels with
      different conjugation sites.
AB  - Chemiluminescent acridinium dimethylphenyl esters are highly sensitive labels
      that are used in automated assays for clinical diagnosis. Light emission from
      these labels and their conjugates is triggered by treatment with alkaline
      peroxide. Conjugation of acridinium ester labels is normally done at the phenol.
      During the chemiluminescent reaction of these acridinium esters, the phenolic
      ester is cleaved and the light emitting acridone moiety is liberated from its
      conjugate partner. In the current study, we report the synthesis of three new
      acridinium esters with conjugation sites at the acridinium nitrogen and compare
      their properties with that of a conventional acridinium ester with a conjugation
      site at the phenol. Our study is the first that provides a direct comparison of
      the emissive properties of acridinium dimethylphenyl esters (free labels and
      protein conjugates) with different conjugation sites, one where the light
      emitting acridone remains attached to its conjugate partner versus conventional
      labeling which results in cleavage of the acridone from the conjugate. Our
      results indicate that the conjugation at the acridinium nitrogen, which also
      alters how the acridinium ring and phenol are oriented with respect to the
      protein surface, has a minimal impact on emission kinetics and emission spectra.
      However, this mode of conjugation to three different proteins led to a
      significant increase in light yield which should be useful for improving the
      assay sensitivity. 

PMID- 25581207
TI  - Colorectal adenomas and diabetes: implications for disease prevention.
AB  - AIM: This study assessed the baseline type II diabetes mellitus (T2DM) risk
      status among overweight patients with screen-detected colorectal adenomas and
      explored the implications of the findings for preventative practice. METHOD:
      Participants aged between 50 and 74 years (73% of whom were men) were recruited
      from four Scottish health boards and assessed for diabetes risk. Participants
      were categorized as at 'high' diabetes risk if glycated haemoglobin (HbA1c) was
      between 6.0 and 6.4% or fasting plasma glucose (FPG) was between 5.5 and 6.9
      mmol/l and as potentially undiagnosed T2DM when HbA1c >= 6.5% or FPG >= 7 mmol/l.
      Secondary outcome measures included anthropometric measurements, blood pressure
      and the plasma lipid profile. The tests were repeated at 12 months and diabetes
      risk categories were reassessed following intervention procedures. RESULTS: Forty
      seven (14.3%) of the 329 participants had a preexisting diagnosis of T2DM. Of the
      remainder with complete biochemistry results (n = 250), 19 (7.6%) were classified
      as having potentially undiagnosed T2DM and 125 (50.0%) as being at high risk of
      developing diabetes. More than a quarter of participants in all categories had
      raised waist circumference, hypertension and plasma lipids, indicative of raised
      cardiovascular risk. At 12 months' follow-up, the diabetes risk category
      diminished in 20% of the intervention group vs 11% in the controls [OR 2.26 (95%
      CI 1.03-4.96)]. CONCLUSION: Our results suggest that a diagnosis of adenoma in
      overweight patients provides a health service opportunity for diabetes
      assessment, prevention and management in a high-risk population at a potentially
      teachable moment.

PMID- 25581209
TI  - A Swedish validation of the Berlin Numeracy Test.
AB  - Recent research has highlighted the importance of considering an individual's
      level of numeracy, that is their numerical abilities, in a vast variety of
      judgment and decision making tasks. To accurately evaluate the influence of
      numeracy requires good and valid measures of the construct. In the present study
      we validate a Swedish version of the Berlin Numeracy Test (Cokely, Galesic,
      Schulz, Ghazal & Garcia-Retamero, 2012). The validation was carried out on both a
      student sample and a sample representative of the Swedish population. The Swedish
      BNT showed sound psychometrical properties in both samples. Further, in both
      samples the BNT had satisfactory convergent and discriminant validity when
      correlating with other measures of numeracy, while not being significantly
      related to measures of personality. With respect to predictive validity the
      results indicated divergent patterns in the two samples. In the student sample,
      participants scoring highest on the BNT outperformed those in the other three
      levels, which did not differ in performance. In contrast, in the population
      sample participants scoring lowest on the BNT performed worse than those in the
      other three levels, which did not differ in performance. Taken together, however,
      the results suggest that the Swedish version of the BNT should be considered a
      valid measure of numeracy in both Swedish student and population representative
      samples. 

PMID- 25581210
TI  - Male germline transmits fetal alcohol epigenetic marks for multiple generations:
      a review.
AB  - Alcohol exposure during fetal and early postnatal development can lead to an
      increased incidence of later life adult-onset diseases. Examples include central
      nervous system dysfunction, depression, anxiety, hyperactivity, and an inability
      to deal with stressful situations, increased infection and cancer. Direct effects
      of alcohol leading to developmental abnormalities often involve epigenetic
      modifications of genes that regulate cellular functions. Epigenetic marks carried
      over from the parents are known to undergo molecular programming events that
      happen early in embryonic development by a wave of DNA demethylation, which
      leaves the embryo with a fresh genomic composition. The proopiomelanocortin
      (Pomc) gene controls neuroendocrine-immune functions and is imprinted by fetal
      alcohol exposure. Recently, this gene has been shown to be hypermethylated
      through three generations. Additionally, the alcohol epigenetic marks on the Pomc
      gene are maintained in the male but not in the female germline during this
      transgenerational transmission. These data suggest that the male-specific
      chromosome might be involved in transmitting alcohol epigenetic marks through
      multiple generations. 

PMID- 25581211
TI  - Response to letter "evaluation of cardiac involvement in caucasian patients with
      skin sarcoidosis".

PMID- 25581212
TI  - Laparoscopic adjustable gastric band tubing erosion into large bowel.

PMID- 25581214
TI  - Highlights from Faraday Discussion 172: Carbon in electrochemistry, Sheffield,
      UK, July 2014.

PMID- 25581213
TI  - Repetitive Transcranial Magnetic Stimulation for Fibromyalgia: Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: Fibromyalgia (FM) is a prevalent chronic pain syndrome with few
      effective therapeutic options available. Repetitive transcranial magnetic
      stimulation (rTMS) is an emerging therapeutic alternative for this condition;
      however, results have been mixed. OBJECTIVES: To evaluate the efficacy of rTMS on
      FM, a comprehensive systematic review and meta-analysis were performed. METHODS:
      Relevant published, English and Portuguese language, randomized clinical trials
      (RCT) comparing rTMS (irrespective of the stimulation protocol) to sham
      stimulation for treating FM pain intensity, depression, and/or quality of life
      (QoL) were identified, considering only those with low risk for bias. Trials
      available until April 2014 were searched through MEDLINE, EMBASE, the Cochrane
      Library Databases, and other 26 relevant medical databases covering from every
      continent. The outcomes for pain, depression, and QoL assessed closest to the
      30th day after rTMS treatment were extracted, and changes from baseline were
      calculated to compare the effects of rTMS vs. placebo. RESULTS: One hundred and
      sixty-three articles were screened, and five with moderate to high quality were
      included. rTMS improved QoL with a moderate effect size (Pooled SMD = -0.472
      95%CI = -0.80 to -0.14); it showed a trend toward reducing pain intensity (SMD = 
      0.64 95%CI = -0.31 to 0.017), but did not change depressive symptoms. CONCLUSION:
      In comparison with sham stimulation, rTMS demonstrated superior effect on the QoL
      of patients with FM 1 month after starting therapy. However, further studies are
      needed to determine optimal treatment protocols and to elucidate the mechanisms
      involved with this effect, which does not seem to be mediated by changes in
      depression, but that may involve pain modulation. Level of evidence 1b.

PMID- 25581215
TI  - Hyperemesis gravidarum, nutritional treatment by nasogastric tube feeding: a 10
      year retrospective cohort study.
AB  - OBJECTIVE: To investigate maternal and fetal outcome in hyperemesis gravidarum
      comparing enteral tube feeding of the mothers with other fluid/nutrition
      regimens. DESIGN: Retrospective hospital-based cohort. SETTING: University
      hospital, Norway. SAMPLE: All 558 women treated for hyperemesis gravidarum 2002
      2011; 273 received water/electrolytes intravenously, 177 received nutritional
      supplements by peripheral line, 107 received enteral feeding by gastroscopically
      positioned nasojejunal tube and 10 received total parenteral nutrition. METHODS:
      Different fluid/nutritional groups were compared by chi-squared or non-parametric
      tests. The influence (odds ratio) of nutritional regimens on having small-for
      gestational-age infants was evaluated by binary logistic regression. MAIN OUTCOME
      MEASURES: Maternal weight gain during hospitalization and pregnancy, birthweight
      and gestational age at delivery. RESULTS: Women receiving enteral nutrition had
      significantly greater weight loss on admission (median 5.0 kg) and at start of
      nutrition (5.5 kg) than the other treatment groups (4.0 kg) (p < 0.001). Enteral
      nutrition was administered for up to 41 days (median 5 days) during
      hospitalization, leading to 0.8 kg weight gain (95% CI 0.5-1.0, p = 0.005). The
      tube-fed women achieved similar weight gain during pregnancy and experienced
      similar incidence of preterm birth or small-for-gestational age compared with the
      other treatment groups. Women with <7 kg total weight gain had increased risk of
      birthweight <2500 g and small-for-gestational-age infants (odds ratio 3.68, 95%
      CI 1.89-7.18, p < 0.001). The nutritional regimen used was not an independent
      risk factor. CONCLUSION: Compared with other fluid/nutrition regimens, enteral
      tube feeding for women affected by severe hyperemesis gravidarum is associated
      with adequate maternal weight gain and favorable pregnancy outcomes.

PMID- 25581216
TI  - Women who conceived with infertility treatment were more likely to receive
      planned cesarean deliveries in Taiwan.
AB  - The objective of this study was to examine the effect of conception with
      infertility treatment on planned cesarean delivery. The participants were from a
      panel of primiparous pregnant women in northern Taiwan. The data analysis
      included 771 women with a singleton pregnancy, of whom 160 had a planned cesarean
      delivery and 611 who had a vaginal delivery. The study women answered structured
      questionnaires during the second and third trimesters of pregnancy, and at one
      month postpartum. Women who conceived with infertility treatment were more likely
      to have planned cesarean deliveries than women who conceived without it (44.7%
      versus 18.1%, p < 0.001; crude odds ratio: 3.66, 95% confidence interval [CI]:
      2.24-5.98). After adjustment for maternal age over 35 years, whether they were
      currently unmarried, selection of time for birth in advance, gestational
      hypertension, and birthweight < 2500 g, women who conceived with infertility
      treatment were 2.95 times (95% CI: 1.47-5.92) more likely to have planned
      cesarean deliveries. The increased risk for planned cesarean deliveries among
      singleton women who conceived with infertility treatment cannot be explained by
      older maternal age or higher number of morbidities during pregnancy. Counseling
      for women who conceive with infertility treatments may be needed to decrease
      unnecessary cesarean deliveries. 

PMID- 25581218
TI  - Risks of imbalanced information on US hospital websites.

PMID- 25581217
TI  - Low-Magnitude Mechanical Stimulation to Improve Bone Density in Persons of
      Advanced Age: A Randomized, Placebo-Controlled Trial.
AB  - Nonpharmacologic approaches to preserve or increase bone mineral density (BMD)
      include whole-body vibration (WBV), but its efficacy in elderly persons is not
      clear. Therefore, we conducted the Vibration to Improve Bone in Elderly Subjects
      (VIBES) trial, a randomized, placebo-controlled trial of 10 minutes of daily WBV
      (0.3g at 37 Hz) in seniors recruited from 16 independent living communities. The
      primary outcomes were volumetric BMD of the hip and spine measured by
      quantitative computed tomography (QCT) and biochemical markers of bone turnover.
      We randomized 174 men and women (89 active, 85 placebo) with T-scores -1 to -2.5
      who were not taking bone active drugs and had no diseases affecting the skeleton
      (mean age 82 +/- 7 years, range 65 to 102). Participants received daily calcium
      (1000 mg) and vitamin D (800 IU). Study platforms were activated using radio
      frequency ID cards providing electronic adherence monitoring; placebo platforms
      resembled the active platforms. In total, 61% of participants in the active arm
      and 73% in the placebo arm completed 24 months. The primary outcomes, median
      percent changes (interquartile range [IQR]) in total volumetric femoral
      trabecular BMD (active group (2.2% [-0.8%, 5.2%]) versus placebo 0.4% [-4.8%,
      5.0%]) and in mid-vertebral trabecular BMD of L1 and L2 (active group (5.3% [
      6.9%, 13.3%]) versus placebo (2.4% [-4.4%, 11.1%]), did not differ between groups
      (all p values > 0.1). Changes in biochemical markers of bone turnover (P1NP and
      sCTX) also were not different between groups (p = 0.19 and p = 0.97,
      respectively). In conclusion, this placebo-controlled randomized trial of daily
      WBV in older adults did not demonstrate evidence of significant beneficial
      effects on volumetric BMD or bone biomarkers; however, the high variability in
      vBMD changes limited our power to detect small treatment effects. The beneficial
      effects of WBV observed in previous studies of younger women may not occur to the
      same extent in elderly individuals.

PMID- 25581220
TI  - A reevaluation of the photolytic properties of 2-hydroxybenzophenone-based UV
      sunscreens: are chemical sunscreens inoffensive?
AB  - The excited states of a set of popular sunscreen agents (2-hydroxybenzophenone,
      oxybenzone, and sulisobenzone) are studied by using femto- and nanosecond time
      resolved spectroscopy. Upon excitation, the compounds undergo an ultrafast
      excited-state intramolecular proton transfer (ESIPT) reaction as the major energy
      wasting process and the rate constant of this reaction is k=2*10(12) s(-1) . The
      ESIPT yields a keto conformer that undergoes a fast, picosecond internal
      conversion decay. However, a photodegradative pathway is a monophotonic H?O bond
      breakage that subsequently leads to trace yields of phenoxyl radicals. Because
      potentially harmful phenoxyl radicals are formed upon irradiation of sunscreen
      agents, care should be taken about their reactivity towards biologically relevant
      compounds. 

PMID- 25581219
TI  - Antiproliferative effects of ZnO, ZnO-MTCP, and ZnO-CuMTCP nanoparticles with
      safe intensity UV and X-ray irradiation.
AB  - In photodynamic therapy (PDT) of cancer both the light and the photosensitizing
      agent are normally harmless, but in combination they could result in selective
      tumor killing. Zinc oxide nanoparticles were synthesized and coated with the
      amino acid cysteine to provide an adequate arm for conjugation with porphyrin
      photosensitizers (meso-tetra (4-carboxyphenyl) porphyrin [MTCP] and CuMTCP).
      Porphyrin-conjugated nanoparticles were characterized by TEM, FTIR, and UV-vis,
      and fluorescence spectrophotometry. The 3-[4, 5-dimethylthiazol-2-yl]-2,5
      diphenyl tetrazolium bromide (MTT) assay was used to measure cell viability in
      the presence or absence of porphyrin conjugates following UV and X-ray
      irradiation. The uptake of the porphyrin-conjugated ZnO nanoparticles by cells
      was detected using fluorescence microscopy. Our results indicated that the
      survival of T-47D cells was significantly compromised in the presence of ZnO-MTCP
      conjugated nanostructures with UV light exposure. Exhibition of cytotoxic
      activity of ZnO-MTCP for human prostate cancer (Du145) cells occurred at a higher
      concentration, indicating the more resistant nature of these tumor cells. ZnO
      CuMTCP showed milder cytotoxic effects in human breast cancer (T-47D) and no
      cytotoxic effects in Du145 with UV light exposure, consistent with its lower
      cytotoxic potency as well as cellular uptake. Surprisingly, none of the ZnO
      porphyrin conjugates exhibited cytotoxic effects with X-ray irradiation, whereas
      ZnO alone exerted cytotoxicity. Thus, ZnO and ZnO-porphyrin nanoparticles with UV
      or X-ray irradiation may provide a suitable treatment option for various cancers.

PMID- 25581221
TI  - Measuring disaster recovery: bouncing back or reaching the counterfactual state?
AB  - How should one measure the recovery of a locale from a disaster? The measurement
      is crucial from a public policy and administration standpoint to determine which
      places should receive disaster assistance, and it affects the performance
      evaluation of disaster recovery programmes. This paper compares two approaches to
      measuring recovery: (i) bouncing back to pre-disaster conditions; and (ii)
      attaining the counterfactual state. The former centres on returning to normalcy
      following disaster-induced losses, whereas the latter focuses on attaining the
      state, using quasi-experimental design, which would have existed if the disaster
      had not occurred. Both are employed here to assess two housing recovery
      indicators (total new units and their valuations) in Hurricane Katrina-affected
      counties (rural and urban). The examination reveals significantly different
      outcomes for the two approaches: counties have not returned to their pre-disaster
      housing conditions, but they do exhibit counterfactual recovery. Moreover, rural
      counties may not be as vulnerable as assumed in the disaster recovery literature.

PMID- 25581222
TI  - Potential of Pteris vittata to Remove Tetracycline Antibiotics from Aquatic
      Media.
AB  - The role of combined arsenic and antibiotics pollution in the environment has
      recently gained more attention. In this study, a new approach to eliminate
      tetracycline antibiotics (TCs) from water, via the fern species Pteris vittata
      (L.), an arsenic hyperaccumulator, was investigated. The encouraging results
      showed that more than half of the TCs could be removed from the water solution
      (with the starting concentration of TCs about 1.0 mg kg(-1) respectively) after
      one day of treatment. No TCs (less than 0.01 mg kg(-1)) were detected in the
      solution after five days of treatment. The results showed that Pteris vittata has
      high ability to eliminate TCs, which makes it suitable for practical application.
      Further research found that TCs concentrations were very low in both the roots
      and the pinnae of Pteris vittata, which indicates that accumulation in the fronds
      is not the main removal mechanism and that degradation in the fronds might be the
      main cause. Present results provide a feasible method for simultaneous removal of
      arsenic and TCs from livestock-polluted wastewater. However, more research work
      should be done before any real-world application is made.

PMID- 25581223
TI  - Retrieval enhances route knowledge acquisition, but only when movement errors are
      prevented.
AB  - Studies of the testing effect have shown that retrieval significantly improves
      learning. However, most of these studies have been restricted to simple types of
      declarative verbal knowledge. Five experiments were designed to explore whether
      testing improves acquisition of route knowledge, which has a procedural component
      consisting of actions to be performed at decision points (Golledge, 1991).
      Participants learned a route through a series of connected rooms in a virtual
      building. Each room contained multiple doors, only one of which led to the next
      room. During encoding, participants were shown the correct sequence of doors in a
      manner similar to global positioning system (GPS) navigation guidance. During
      subsequent exposures to the route, participants were either shown the correct
      sequence again or had to recall the sequence from memory. Participants later
      completed a final test in which they traversed the route without guidance or
      feedback. Testing improved route memory compared to studying, but only when
      participants were given feedback about the correct door prior to moving through
      the room. When feedback occurred after moving to an incorrect door, testing
      resulted in worse performance compared to studying. These findings parallel work
      on errorless learning, in which procedural skills are acquired more quickly when
      errors are minimized during learning.

PMID- 25581224
TI  - On the (elusive) role of oral motor-movements in fluency-based memory illusions.
AB  - It is well established that the ease with which a stimulus is processed affects
      many different types of evaluative judgments. Recently, it has been proposed that
      for verbal stimuli the effect of fluency on such judgments is mediated by the
      muscles that are involved in speech (Topolinski & Strack, 2009, 2010). Evidence
      for this claim can be found in studies that have shown that fluency effects are
      eliminated if such judgments are made while these muscles are otherwise engaged
      (such as while chewing gum or eating). Additional research has found that oral
      motor tasks block familiarity-based responding on recognition memory tasks
      (Topolinski, 2012). The current study investigated the effect of an oral-motor
      task on recognition memory. Of particular interest was whether the fluency
      blocking effects of an oral-motor task would extend to fluency-based illusions of
      recognition memory. Although we found robust fluency-based illusions of
      familiarity, we did not find that the effects were modulated by the nature of the
      concurrent task (gum-chewing vs. a manual-motor task). Moreover, we found no
      evidence that oral-motor tasks affected recognition more generally, nor did we
      find that an oral-motor task modulated affective ratings to repeated stimuli. We
      were also unable to replicate the finding that an oral-motor task blocks the
      false fame effect (Topolinski & Strack, 2010). These results call into question
      the assertion that oral-motor movements mediate fluency effects in recognition
      memory and other evaluative judgments.

PMID- 25581225
TI  - Semantic generalization in implicit language learning.
AB  - Despite many years of investigation into implicit learning in nonlinguistic
      domains, the potential for implicit learning to deliver the kinds of
      generalizations that underlie natural language competence remains unclear. In a
      series of experiments, we investigated implicit learning of the semantic
      preferences of novel verbs, specifically, whether they collocate with abstract or
      concrete nouns. After reading sentences containing the verbs, participants were
      required to judge the familiarity of pairs of novel verbs and nouns and to
      indicate their confidence or the basis of their judgment (i.e., guess, intuition,
      memory). Although all of the words had occurred in the texts, none of the
      critical items had actually occurred together. However, endorsement rates were
      significantly higher for pairs that respected the semantic preference rules than
      those that did not. Through analysis of subjective measures and verbal report, we
      argue that, for the majority of participants, this effect was based on
      unconscious knowledge. We argue that implicit learning of the kind of
      generalizations underlying semantic preferences is possible even after limited
      exposure.

PMID- 25581226
TI  - Parafoveal-on-foveal effects of emotional word semantics in reading Chinese
      sentences: evidence from eye movements.
AB  - Despite the well-known influence of emotional meaning on cognition, relatively
      less is known about its effects on reading behavior. We investigated whether
      fixation behavior during the reading of Chinese sentences is influenced by
      emotional word meaning in the parafovea. Two-character target words embedded into
      the same sentence frames provided emotionally positive, negative, or neutral
      contents. Fixation durations on neutral pretarget words were prolonged for
      positive parafoveal words and for highly frequent negative parafoveal words. In
      addition, fixation durations on foveal emotional words were shorter than those on
      neutral words. We also found that the role of emotional words varied as a
      function of their valence during foveal and parafoveal processing. These findings
      suggest a processing advantage for emotional words relative to emotionally
      neutral stimuli in foveal and parafoveal vision. We discuss implications for the
      notion of attention attraction due to emotional content.

PMID- 25581227
TI  - Supramolecular buffering by ring-chain competition.
AB  - Recently, we reported an organocatalytic system in which buffering of the
      molecular catalyst by supramolecular interactions results in a robust system
      displaying concentration-independent catalytic activity. Here, we demonstrate the
      design principles of the supramolecular buffering by ring-chain competition using
      a combined experimental and theoretical approach. Our analysis shows that
      supramolecular buffering of a molecule is caused by its participation as a chain
      stopper in supramolecular ring-chain equilibria, and we reveal here the influence
      of various thermodynamic parameters. Model predictions based on independently
      measured equilibrium constants corroborate experimental data of several molecular
      systems in which buffering occurs via competition between cyclization, growth of
      linear chains, and end-capping by the chain-stopper. Our analysis reveals that
      the effective molarity is the critical parameter in optimizing the broadness of
      the concentration regime in which supramolecular ring-chain buffering occurs as
      well as the maximum concentration of the buffered molecule. To conclude, a side
      by-side comparison of supramolecular ring-chain buffering, pH buffering, and
      molecular titration is presented. 

PMID- 25581229
TI  - The puzzling attractiveness of male shame.
AB  - Two studies examined the mechanisms underlying North American women's previously
      documented attraction to men displaying the nonverbal expression of shame (Tracy
      and Beall, 2011). In Study 1, American women at high-conception risk were found
      to be less attracted to men displaying shame compared to women at low-conception
      risk, suggesting that male shame displays indicate poor genetic fitness. In Study
      2, Indian women were found to be less attracted to men displaying shame than
      American women, suggesting that American women's tendency to find shame
      displaying men attractive is likely due to local socio-cultural factors rather
      than to universal genetically encoded predispositions. Together, findings suggest
      that the attractiveness of male shame displays, previously documented in several
      North American samples, is best explained by cultural rather than biological
      factors. 

PMID- 25581228
TI  - Polythiophene nanofibril bundles surface-embedded in elastomer: a route to a
      highly stretchable active channel layer.
AB  - A stretchable polymer channel layer for organic field-effect transistors is
      obtained by spin-coating a blend solution of polythiophene and rubber polymer. A
      network of the polythiophene nanofibril bundles surface-embedded in the rubber
      matrix allows large stretchability of the polythiophene film layer. 

PMID- 25581230
TI  - Patellofemoral Dysfunction in Sports Trochleoplasty: Indications and Techniques.
AB  - Patellofemoral instability (PFI) is a pathological knee syndrome that frequently
      affects young patients. The patellofemoral joint's structural morphology is the
      determining factor in the extent of PFI. Structural factors that play leading
      roles in patellofemoral stability can be classified into static (bone
      morphology), passive (ligamentous), and active (muscular). The predominant static
      factor leading to patella dislocation and thus patellofemoral dysfunction is
      trochlear dysplasia, which we focus on in this review. After orienting clinical
      examinations, MRI can provide the best information about trochlear dysplasia.
      This includes trochlear shape, orientation, and tibial tuberosity to trochlear
      groove distance. In convex trochleas or trochlea dysplasia with PFI at flexion
      over 30 degrees, we recommend performing a deepening trochleoplasty to correct
      for static pathomorphology. In this review, we will focus on the pathology of
      trochlea dysplasia, its role in PFI, the correct indication for trochleoplasty as
      a primary intervention, and the role of a simultaneous medial patellofemoral
      ligament reconstruction. 

PMID- 25581231
TI  - Modeling, simulation, and fabrication of a fully integrated, acid-stable,
      scalable solar-driven water-splitting system.
AB  - A fully integrated solar-driven water-splitting system comprised of WO3 /FTO/p(+)
      n Si as the photoanode, Pt/TiO2 /Ti/n(+) p Si as the photocathode, and Nafion as
      the membrane separator, was simulated, assembled, operated in 1.0 M HClO4 , and
      evaluated for performance and safety characteristics under dual side
      illumination. A multi-physics model that accounted for the performance of the
      photoabsorbers and electrocatalysts, ion transport in the solution electrolyte,
      and gaseous product crossover was first used to define the optimal geometric
      design space for the system. The photoelectrodes and the membrane separators were
      then interconnected in a louvered design system configuration, for which the
      light-absorbing area and the solution-transport pathways were simultaneously
      optimized. The performance of the photocathode and the photoanode were separately
      evaluated in a traditional three-electrode photoelectrochemical cell
      configuration. The photocathode and photoanode were then assembled back-to-back
      in a tandem configuration to provide sufficient photovoltage to sustain solar
      driven unassisted water-splitting. The current-voltage characteristics of the
      photoelectrodes showed that the low photocurrent density of the photoanode
      limited the overall solar-to-hydrogen (STH) conversion efficiency due to the
      large band gap of WO3 . A hydrogen-production rate of 0.17 mL hr(-1) and a STH
      conversion efficiency of 0.24 % was observed in a full cell configuration for >20
      h with minimal product crossover in the fully operational, intrinsically safe,
      solar-driven water-splitting system. The solar-to-hydrogen conversion efficiency,
      etaSTH , calculated using the multiphysics numerical simulation was in excellent
      agreement with the experimental behavior of the system. The value of etaSTH was
      entirely limited by the performance of the photoelectrochemical assemblies
      employed in this study. The louvered design provides a robust platform for
      implementation of various types of photoelectrochemical assemblies, and can
      provide an approach to significantly higher solar conversion efficiencies as new
      and improved materials become available.

PMID- 25581232
TI  - Oxidative degradation of polysorbate surfactants studied by liquid chromatography
      mass spectrometry.
AB  - Polysorbates (PSs), as acquired from manufacturing processes and chemical nature
      of fatty acids (FAs) used in production of biotherapeutic formulations, are
      heterogeneous mixtures of structurally related compounds, covering a wide range
      of physicochemical properties. Such complexity presents a certain challenge for
      analysis of these important surfactants and demands the use of methods offering
      sufficient resolution to monitor individual classes of species and detect changes
      upon stress. A liquid chromatography mass spectrometry method, benefiting from
      the use of low m/z marker ions, simplifies profiling of PSs by providing detailed
      information on FA composition even of chromatographically overlapping peaks. The
      ability of the method to monitor individual components and follow their changes
      because of oxidative stress was explored. A water-soluble azo compound was used
      as a model oxidizer. Major degradation products of PS 80, because of reactions
      involving double bond, were identified as oxo-C9:0, keto-C18:1, hydroxyl-C18:1,
      epoxy-C18:0, and hydroperoxy-C18:1. Stability of PS 20 components was found to
      depend on the carbon number of polyethoxylated (POE) sorbitan FA ester and its
      order. Rates of oxidative degradation increased with the length of the FA ester
      and, moreover, POE sorbitan diesters degraded significantly faster in comparison
      to the corresponding monoesters upon the oxidative stress.

PMID- 25581233
TI  - Chronic traumatic encephalopathy: historical origins and current perspective.
AB  - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is
      most often identified in postmortem autopsies of individuals exposed to
      repetitive head impacts, such as boxers and football players. The neuropathology
      of CTE is characterized by the accumulation of hyperphosphorylated tau protein in
      a pattern that is unique from that of other neurodegenerative diseases, including
      Alzheimer's disease. The clinical features of CTE are often progressive, leading
      to dramatic changes in mood, behavior, and cognition, frequently resulting in
      debilitating dementia. In some cases, motor features, including parkinsonism, can
      also be present. In this review, the historical origins of CTE are revealed and
      an overview of the current state of knowledge of CTE is provided, including the
      neuropathology, clinical features, proposed clinical and pathological diagnostic
      criteria, potential in vivo biomarkers, known risk factors, and treatment
      options. 

PMID- 25581234
TI  - Depression and cognition in the elderly.
AB  - This review provides an overview of the relationship between depression and
      cognition in the elderly, with an emphasis on psychotherapies and
      nonpharmacologic approaches. We first review the clinical presentation of late
      life depression and comorbid cognitive impairment, as well as the epidemiology
      and risk factors for cognitive impairment in late-life depression and the
      temporal relationship between depression and cognitive impairment. Next, we
      discuss the salient topic of elderly suicide and cognitive impairment. We then
      touch briefly on the neuropsychological deficits, biomarkers, and neuroimaging
      findings in late-life depression with comorbid cognitive impairment. We then
      focus most of this review on psychotherapies and nontraditional treatments for
      late-life depression with comorbid cognitive impairment and examine what
      evidence, if any, exists of the cognitive and functional benefits of these
      treatments. Finally, we examine the cognitive effects of pharmacologic treatments
      and brain stimulation therapies. 

PMID- 25581236
TI  - Etiologic, phenomenologic, and endophenotypic overlap of schizophrenia and
      bipolar disorder.
AB  - This review examines the history of psychiatric nosology, with particular
      reference to the nineteenth-century origins of the concepts of manic-depressive
      illness and schizophrenia as distinct clinical syndromes and their evolution and
      diagnostic refinement over time. I document how the terminology applied to these
      entities has generated controversy, and discuss the ways in which the resulting
      diagnostic entities as defined by pure phenomenological symptom descriptors fail
      to capture discrete diagnostic distinctions, leading some researchers to posit an
      illness continuum rather than separate disorders. Furthermore, the two syndromes
      overlap substantially on multiple biologic measures, and clarity is lacking as to
      the underlying etiology and pathology necessary to move from descriptions of
      clinical syndromes to diseases. I next examine how biologically based
      classifications agnostic to conventional diagnostic schemes may be useful and how
      these are being implemented in practice, and conclude by summarizing where such
      approaches are likely to lead. 

PMID- 25581235
TI  - The development and course of bipolar spectrum disorders: an integrated reward
      and circadian rhythm dysregulation model.
AB  - In this article, we present and review the evidence for two major biopsychosocial
      theories of the onset and course of bipolar spectrum disorders (BSDs) that
      integrate behavioral, environmental, and neurobiological mechanisms: the reward
      hypersensitivity and the social/circadian rhythm disruption models. We describe
      the clinical features, spectrum, age of onset, and course of BSDs. We then
      discuss research designs relevant to demonstrating whether a hypothesized
      mechanism represents a correlate, vulnerability, or predictor of the course of
      BSDs, as well as important methodological issues. We next present the reward
      hypersensitivity model of BSD, followed by the social/circadian rhythm disruption
      model of BSD. For each model, we review evidence regarding whether the proposed
      underlying mechanism is associated with BSDs, provides vulnerability to the onset
      of BSDs, and predicts the course of BSDs. We then present a new integrated
      reward/circadian rhythm (RCR) dysregulation model of BSD and discuss how the RCR
      model explains the symptoms, onset, and course of BSDs. We end with
      recommendations for future research directions. 

PMID- 25581239
TI  - Obsessive-compulsive and related disorders: a critical review of the new
      diagnostic class.
AB  - The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders
      includes a new class of obsessive-compulsive and related disorders (OCRDs) that
      includes obsessive-compulsive disorder (OCD) and a handful of other putatively
      related conditions. Although this new category promises to raise awareness of
      underrecognized and understudied problems, its empirical validity and practical
      utility are questionable. This article reviews the phenomenology of OCD and then
      presents a critical analysis of the arguments underlying the new OCRD class. This
      analysis leads to a rejection of the OCRD classification on both scientific and
      logical grounds. The article closes with a discussion of the treatment
      implications of the OCRDs approach. 

PMID- 25581237
TI  - fMRI functional connectivity applied to adolescent neurodevelopment.
AB  - The exponential rise in the number of functional brain connectivity studies,
      particularly those examining intrinsic functional connectivity (iFC) at rest, and
      the promises of this work for unraveling the ontogeny of functional neural
      systems motivate this review. Shortly before this explosion in functional
      connectivity research, developmental neuroscientists had proposed theories based
      on neural systems models to explain behavioral changes, particularly in
      adolescence. The current review presents recent advances in imaging in brain
      connectivity research, which provides a unique tool for the study of neural
      systems. Understanding the potential of neuroimaging for refining
      neurodevelopmental models of brain function requires a description of various
      functional connectivity approaches. In this review, we describe task-based and
      resting-state functional magnetic resonance imaging (fMRI) analytic strategies,
      but we focus on iFC findings from resting-state data to describe general
      developmental trajectories of brain network organization. Finally, we use the
      example of drug addiction to frame a discussion of psychopathology that emerges
      in adolescence. 

PMID- 25581240
TI  - Clinical features, cognitive biases, and treatment of body dysmorphic disorder.
AB  - In the past two decades, research advances have enhanced our understanding of the
      clinical features, cognitive biases, and treatment of body dysmorphic disorder
      (BDD). In this review, we critically examine the current state of the evidence on
      the proposed cognitive and emotional processing mechanisms of BDD. We describe
      how major findings in these areas made unique contributions to the development of
      an empirically informed cognitive-behavioral model of BDD, which in turn
      facilitated the translation of research to treatment strategies. Finally, we
      outline important areas of future research. 

PMID- 25581241
TI  - Thinking about rumination: the scholarly contributions and intellectual legacy of
      Susan Nolen-Hoeksema.
AB  - Our article reviews and celebrates Susan Nolen-Hoeksema's remarkable
      contributions to psychological and clinical science, focusing on her vast body of
      theoretical and empirical work and her influence on colleagues and students.
      Susan spent her career trying to understand how and why a style of regulating
      emotions called rumination increases vulnerability to depression and exacerbates
      and perpetuates negative moods. More broadly, we describe research by Susan and
      her colleagues on the predictors of depression in childhood and adolescence;
      gender differences in depression and rumination in adolescence and adulthood;
      roots, correlates, and adverse consequences of ruminative response styles; and
      rumination as a transdiagnostic risk factor for not only depression but also a
      host of psychological disorders, including anxiety, substance abuse, and eating
      disorders. Susan's intellectual legacy is evident in her impressive publication
      and citation record, the clinical applications of her work, and the flourishing
      careers of the students she mentored. 

PMID- 25581242
TI  - Emotion regulation and psychopathology.
AB  - Emotional problems figure prominently in many clinical conditions. Recent efforts
      to explain and treat these conditions have emphasized the role of emotion
      dysregulation. However, emotional problems are not always the result of emotion
      dysregulation, and even when emotional problems do arise from emotion
      dysregulation, it is necessary to specify precisely what type of emotion
      dysregulation might be operative. In this review, we present an extended process
      model of emotion regulation, and we use this model to describe key points at
      which emotion-regulation difficulties can lead to various forms of
      psychopathology. These difficulties are associated with (a) identification of the
      need to regulate emotions, (b) selection among available regulatory options, (c)
      implementation of a selected regulatory tactic, and (d) monitoring of implemented
      emotion regulation across time. Implications and future directions for basic
      research, assessment, and intervention are discussed. 

PMID- 25581238
TI  - Self-reported experiences of discrimination and health: scientific advances,
      ongoing controversies, and emerging issues.
AB  - Over the past two decades, research examining the impact of self-reported
      experiences of discrimination on mental and physical health has increased
      dramatically. Studies have found consistent associations between exposure to
      discrimination and a wide range of Diagnostic and Statistical Manual of Mental
      Disorders (DSM)-diagnosed mental disorders as well as objective physical health
      outcomes. Associations are seen in cross-sectional as well as longitudinal
      studies and persist even after adjustment for confounding variables, including
      personality characteristics and other threats to validity. However, controversies
      remain, particularly around the best approach to measuring experiences of
      discrimination, the significance of racial/ethnic discrimination versus overall
      mistreatment, the need to account for "intersectionalities," and the importance
      of comprehensive assessments. These issues are discussed in detail, along with
      emerging areas of emphasis including cyber discrimination, anticipatory stress or
      vigilance around discrimination, and interventions with potential to reduce the
      negative effects of discrimination on health. We also discuss priorities for
      future research and implications for interventions and policy. 

PMID- 25581243
TI  - Clinical dysfunction and psychosocial interventions: the interplay of research,
      methods, and conceptualization of challenges.
AB  - I describe the development and course of my research in studying clinical
      dysfunction among children, adolescents, and adults. This is an autobiographical
      account that highlights programs of research, career moves, and experiences along
      the way that were particularly influential. Research on specific topics and the
      methods to study them were inherently fascinating but invariably led me to
      broader issues well beyond what I was studying. The research alerted me to how
      and why current methods, assumptions, and research practices might be
      constraining and perhaps slightly misguided. My research and specific findings in
      a given area were not necessarily part of any particular breakthrough but rather
      helped me see how more, different, and better work was needed. Collaborations
      with a diverse set of colleagues and models from other disciplines than
      psychology helped me conceptualize the goals of research on a given topic (e.g.,
      developing evidence-based treatments, reducing the burden of mental illness,
      promoting a sustainable environment to mitigate climate change) and propose a
      shift from current practices as a means to obtain them. 

PMID- 25581244
TI  - Recent advances in autism research as reflected in DSM-5 criteria for autism
      spectrum disorder.
AB  - This article provides a selective review of advances in scientific knowledge
      about autism spectrum disorder (ASD), using DSM-5 (Diagnostic and Statistical
      Manual of Mental Disorders, fifth edition) diagnostic criteria as a framework for
      the discussion. We review literature that prompted changes to the organization of
      ASD symptoms and diagnostic subtypes in DSM-IV, and we examine the rationale for
      new DSM-5 specifiers, modifiers, and severity ratings as well as the introduction
      of the diagnosis of social (pragmatic) communication disorder. Our goal is to
      summarize and critically consider the contribution of clinical psychology
      research, along with that of other disciplines, to the current conceptualization
      of ASD. 

PMID- 25581245
TI  - Serum complement inactivation unveiled prepregnancy donor-specific HLA antibodies
      leading to postpartum kidney graft loss.

PMID- 25581246
TI  - Paternal epigenetic effects of population density on locust phase-related
      characteristics associated with heat-shock protein expression.
AB  - Many species exhibit transgenerational plasticity by which environmental cues
      experienced by either parent can be transmitted to their offspring, resulting in
      phenotypic variants in offspring to match ancestral environments. However, the
      manner by which paternal experiences affect offspring plasticity through
      epigenetic inheritance in animals generally remains unclear. In this study, we
      examined the transgenerational effects of population density on phase-related
      traits in the migratory locust Locusta migratoria. Using an experimental design
      that explicitly controls genetic background, we found that the effects of crowd
      or isolation rearing on phase plasticity could be inherited to the offspring. The
      isolation of gregarious locusts resulted in reduced weight in offspring eggs and
      altered morphometric traits in hatchlings, whereas crowding of solitarious
      locusts exhibited opposite effects. The consequences of density changes were
      transmitted by both maternal and paternal inheritance, although the expression of
      paternal effects was not as pronounced as that of maternal effects. Prominent
      expression of heat-shock proteins (Hsps), such as Hsp90, Hsp70 and Hsp20.6, could
      be triggered by density changes. Hsps were significantly upregulated upon
      crowding but downregulated upon isolation. The variation in parental Hsp
      expression was also transmitted to the offspring, in which the pattern of
      inheritance was consistent with that of phase characteristics. These results
      revealed a paternal effect on phase polyphenism and Hsp expression induced by
      population density, and defined a model system that could be used to study the
      paternal epigenetic inheritance of environmental changes. 

PMID- 25581247
TI  - The induction phenomenon and catalytic deactivation of thiolate-stabilized
      raspberry-like polymer composites coated with gold nanoparticles.
AB  - Alkylthiolate ligands play dual roles in metal nanoparticles-coated polymer
      composite catalysts: stabilizer and deactivator. Herein, individual raspberry
      like polymer composite spheres coated with gold nanoparticles were separated from
      each other in the presence of 6-mercaptohexanoic acid or 3-mercaptopropionic acid
      ligands. Effects of thiolate ligands on the induction time and the catalytic
      activity of such non-aggregated polymer composites were investigated
      experimentally and theoretically in the 4-nitrophenol/NaBH4 model reaction from
      the following aspects: ligand surface coverage, chain order and chain length.
      With the increase in alkylthiolate surface coverage and chain order on composite
      particles, the induction time increases first and then decreases, which can be
      explained based on spontaneous dynamic surface restructuring and electron
      injection from borohydride ions to the gold nanoparticle surface. The catalytic
      activity is compromised with the existence of thiolate ligands, but is enhanced
      with increasing alkylthiolate ligand coverage, which can be ascribed to sulfur
      induced electronic charge depletion of the gold nanoparticles. The increment of
      CH2 in alkylthiolate chains results in the increase of induction time and the
      decrease of the catalytic activity, which can be attributed to the steric
      hindrance effect. The reactant addition sequence was also found to affect the
      induction time and the catalytic activity, which can be partially credited to
      NaBH4 reductant-induced desorption of thiolate ligands. 

PMID- 25581248
TI  - Benzannulation of heterocyclic frameworks by 1,1-carboboration pathways.
AB  - A small series of S- and N-heterocyclic 1,2-bis(trimethylsilylethynyl)arenes (2,
      9, and 12) react with the strongly electrophilic borane B(C6F5)3 in consecutive
      1,1-carboboration sequences to benzannulated heterocyclic systems. With this
      approach, highly substituted carbazole (6), benzothiophene (10), and quinoline
      (14) derivatives can be synthesized. While benzannulation occurs in all three
      cases, the reactions are quite different in detail. Finally, one-pot deborylation
      reactions lead to hydroxy-hetarenes, as demonstrated for the hydroxy-carbazole 7
      and the hydroxy-benzothiophene 11. 

PMID- 25581249
TI  - Filamentary switching: synaptic plasticity through device volatility.
AB  - Replicating the computational functionalities and performances of the brain
      remains one of the biggest challenges for the future of information and
      communication technologies. Such an ambitious goal requires research efforts from
      the architecture level to the basic device level (i.e., investigating the
      opportunities offered by emerging nanotechnologies to build such systems).
      Nanodevices, or, more precisely, memory or memristive devices, have been proposed
      for the implementation of synaptic functions, offering the required features and
      integration in a single component. In this paper, we demonstrate that the basic
      physics involved in the filamentary switching of electrochemical metallization
      cells can reproduce important biological synaptic functions that are key
      mechanisms for information processing and storage. The transition from short- to
      long-term plasticity has been reported as a direct consequence of filament growth
      (i.e., increased conductance) in filamentary memory devices. In this paper, we
      show that a more complex filament shape, such as dendritic paths of variable
      density and width, can permit the short- and long-term processes to be controlled
      independently. Our solid-state device is strongly analogous to biological
      synapses, as indicated by the interpretation of the results from the framework of
      a phenomenological model developed for biological synapses. We describe a single
      memristive element containing a rich panel of features, which will be of benefit
      to future neuromorphic hardware systems. 

PMID- 25581250
TI  - Survival of adults with systemic sclerosis following lung transplantation: a
      nationwide cohort study.
AB  - OBJECTIVE: Many transplant programs are hesitant to offer lung transplantation to
      patients with systemic sclerosis (SSc) due to concerns about extrapulmonary
      involvement that might affect survival. The aim of this study was to determine
      whether adults with SSc have higher 1-year mortality rates after lung
      transplantation compared to those with interstitial lung disease (ILD) or
      pulmonary arterial hypertension (PAH) not due to SSc. METHODS: Using data
      provided by the United Network for Organ Sharing, we performed a retrospective
      cohort study of 229 adults with SSc, 201 with PAH, and 3,333 with ILD who
      underwent lung transplantation in the US between May 4, 2005 and September 14,
      2012. We examined associations between diagnosis and 1-year survival after lung
      transplantation using stratified Cox models adjusted for recipient, donor, and
      procedure factors. RESULTS: Adults with SSc undergoing lung transplantation in
      the US had a multivariable-adjusted 48% relative increase in the 1-year mortality
      rate compared to those with non-SSc-related ILD (hazard ratio 1.48 [95%
      confidence interval 1.01-2.17]). However, we did not detect a difference in the
      risk of death at 1 year between those with SSc and those with non-SSc-related PAH
      (hazard ratio 0.85 [95% confidence interval 0.50-1.44]). CONCLUSION: A diagnosis
      of SSc may confer an increased risk of death 1 year following lung
      transplantation compared to a diagnosis of ILD, but this risk is similar to that
      of PAH, a widely accepted indication for lung transplantation. Future work should
      identify modifiable risk factors that can improve transplant outcomes in this
      population.

PMID- 25581251
TI  - Association between health-related quality of life and symptoms in patients with
      chronic constipation: an integrated analysis of three phase 3 trials of
      prucalopride.
AB  - BACKGROUND: Prucalopride is a high-affinity 5-HT4 receptor agonist for the
      treatment of chronic constipation. The aims of this study were to investigate the
      relationship between health-related quality of life (HRQoL) and symptoms of
      constipation, and to assess the response of HRQoL to treatment using integrated
      data from three phase III trials of prucalopride. METHODS: This was an integrated
      analysis of data from three pivotal multicenter, double-blind, randomized,
      placebo-controlled, parallel-group trials (ClinicalTrials.gov Identifiers:
      NCT00488137, NCT00483886 and NCT00485940). Relationships were investigated
      between Patient Assessment of Constipation Quality of Life (PAC-QOL) scores,
      Patient Assessment of Constipation Symptoms (PAC-SYM) scores, bowel movement
      frequency (assessed using daily diaries), and treatment. KEY RESULTS: Patients
      treated with prucalopride 2 mg (n = 659) and placebo (n = 661) were included in
      the analysis. An improvement in PAC-SYM scores correlated well with an
      improvement in PAC-QOL overall score (r = 0.711) and satisfaction subscale score
      (r = 0.589). After 12 weeks, PAC-QOL overall score and satisfaction subscale
      score significantly (p < 0.001) improved by >= 1 point (clinically relevant) in
      36.5% and 44.1% of patients treated with prucalopride, compared with 18.5% and
      22.4% with placebo respectively. Moreover, 39.0% of patients with an improvement
      in satisfaction of >= 1 point achieved >= 3 spontaneous complete bowel
      movements/week, compared with 7.4% of those with no improvement in satisfaction
      (<1 point). CONCLUSIONS & INFERENCES: Improvements in PAC-QOL overall score and
      satisfaction score were associated with improvements in symptoms of chronic
      constipation. Compared with placebo, treatment with prucalopride significantly
      improved HRQoL.

PMID- 25581252
TI  - Current unmet needs of cancer survivors: analysis of open-ended responses to the
      American Cancer Society Study of Cancer Survivors II.
AB  - BACKGROUND: Cancer survivors may continue to experience psychosocial and physical
      needs related to their cancer experience for many years after treatment. The
      specification of these needs across cancer types and by survivor characteristics
      may lead to better prevention approaches and clinical responses. Mixed methods
      were used to examine responses to an open-ended question about current unmet
      needs from a survey of 2-, 5-, and 10-year cancer survivors. METHODS: Qualitative
      techniques were used to code themes of unmet needs from open-ended responses.
      These themes were then examined with quantitative techniques to describe the
      frequency of unmet needs across disease subgroups and demographic subgroups of
      survivors. RESULTS: There were 1514 responses to the open-ended question on unmet
      needs. Respondents ranged in age from 24 to 97 years and included proportionately
      more women, and 18% were minorities (black and Hispanic). Sixteen themes of unmet
      needs were identified. The number and type of unmet needs were not associated
      with the time since cancer treatment. Breast cancer survivors identified more
      unmet needs than other survivors. Male survivors and especially prostate cancer
      survivors identified personal control problems as current needs. Older cancer
      survivors identified fewer unmet needs on average than younger survivors.
      CONCLUSIONS: This analysis of an open-ended question on unmet needs extends our
      understanding of how cancer survivors perceive problems related to cancer. How
      cancer-related needs change over time and differ by sex, race, and ethnicity and
      how problems with personal control become manifest are areas of inquiry requiring
      further research.

PMID- 25581253
TI  - Coarse-grained simulation study of sequence effects on DNA hybridization in a
      concentrated environment.
AB  - A novel coarse-grained model is developed to elucidate thermodynamics and kinetic
      mechanisms of DNA self-assembly. It accounts for sequence and solvent conditions
      to capture key experimental results such as sequence-dependent thermal property
      and salt-dependent persistence length of ssDNA and dsDNA. Moreover, constant
      temperature simulations on two single strands of a homogeneous sequence show two
      main mechanisms of hybridization: a slow slithering mechanism and a one-order
      faster zippering mechanism. Furthermore, large-scale simulations at a high DNA
      strand concentration demonstrate that DNA self-assembly is a robust and
      enthalpically driven process in which the formation of double helices is
      deciphered to occur via multiple self-assembly pathways including the strand
      displacement mechanism. However, sequence plays an important role in shifting the
      majority of one pathway over the others and controlling size distribution of self
      assembled aggregates. This study yields a complex picture on the role of sequence
      on programmable self-assembly and demonstrates a promising simulation tool that
      is suitable for studies in DNA nanotechnology. 

PMID- 25581255
TI  - Photomobile polymer materials: photoresponsive behavior of cross-linked liquid
      crystalline polymers with mesomorphic diarylethenes.
AB  - Cross-linked liquid-crystalline (LC) polymers with a mesomorphic diarylethene
      were prepared to demonstrate a versatile strategy for cross-linked photochromic
      LC polymers as photomobile materials. Upon exposure to UV light to cause
      photocyclization of the diarylethene chromophore, the cross-linked polymer films
      bend toward an actinic light source. By irradiation with visible light to cause a
      closed-ring to open-ring isomerization, the bent films revert to the initial flat
      state. Without visible-light irradiation, the bent films remain bent even at 120 
      degrees C, indicating high thermal stability of the cross-linked diarylethene LC
      polymers. 

PMID- 25581254
TI  - Impact of concurrent foot pain on health and functional status in people with
      knee osteoarthritis: data from the osteoarthritis initiative.
AB  - OBJECTIVE: To document the prevalence of foot pain and foot pain laterality in
      people with knee osteoarthritis (OA) and to examine its impact on health and
      function. METHODS: Participants from the Progression subcohort (n = 1,255, ages
      45-79 years) of the Osteoarthritis Initiative with symptomatic tibiofemoral knee
      OA were included. Prevalence of foot pain, defined as pain in the foot/ankle, and
      foot pain laterality were determined. Health status was evaluated using the
      Western Ontario and McMaster Universities Osteoarthritis Index, the Short Form-12
      Health Survey, and the Center for Epidemiological Studies Depression Scale.
      Function was assessed using the 20-meter walk test (WT) and a repeated chair
      stand test. Differences in health and functional measures were compared between
      groups with and without foot pain using multivariate analysis of covariance.
      RESULTS: One-fourth (n = 317 [25%]) of people with knee OA experienced concurrent
      foot pain, with the majority (n = 174 [55%]) reporting pain in both feet. After
      adjusting for covariates, people with foot pain scored worse on all health
      measures and on the 20-meter WT, compared to those without (P < 0.05).
      Differences in health and function were found between the bilateral and
      ipsilateral foot pain groups compared to those without foot pain (P < 0.05), but
      no differences were found with the contralateral group. CONCLUSION: Foot pain is
      common in people with knee OA, and bilateral and ipsilateral foot pain adversely
      affect health and function, suggesting laterality is important. Further research
      is needed to establish the mechanism and interaction of pathology at these sites
      and to evaluate foot pain treatment in this population.

PMID- 25581257
TI  - The effectiveness and risks of long-term opioid therapy for chronic pain: a
      systematic review for a National Institutes of Health Pathways to Prevention
      Workshop.
AB  - BACKGROUND: Increases in prescriptions of opioid medications for chronic pain
      have been accompanied by increases in opioid overdoses, abuse, and other harms
      and uncertainty about long-term effectiveness. PURPOSE: To evaluate evidence on
      the effectiveness and harms of long-term (>3 months) opioid therapy for chronic
      pain in adults. DATA SOURCES: MEDLINE, the Cochrane Central Register of
      Controlled Trials, the Cochrane Database of Systematic Reviews, PsycINFO, and
      CINAHL (January 2008 through August 2014); relevant studies from a prior review;
      reference lists; and ClinicalTrials.gov. STUDY SELECTION: Randomized trials and
      observational studies that involved adults with chronic pain who were prescribed
      long-term opioid therapy and that evaluated opioid therapy versus placebo, no
      opioid, or nonopioid therapy; different opioid dosing strategies; or risk
      mitigation strategies. DATA EXTRACTION: Dual extraction and quality assessment.
      DATA SYNTHESIS: No study of opioid therapy versus no opioid therapy evaluated
      long-term (>1 year) outcomes related to pain, function, quality of life, opioid
      abuse, or addiction. Good- and fair-quality observational studies suggest that
      opioid therapy for chronic pain is associated with increased risk for overdose,
      opioid abuse, fractures, myocardial infarction, and markers of sexual
      dysfunction, although there are few studies for each of these outcomes; for some
      harms, higher doses are associated with increased risk. Evidence on the
      effectiveness and harms of different opioid dosing and risk mitigation strategies
      is limited. LIMITATIONS: Non-English-language articles were excluded, meta
      analysis could not be done, and publication bias could not be assessed. No
      placebo-controlled trials met inclusion criteria, evidence was lacking for many
      comparisons and outcomes, and observational studies were limited in their ability
      to address potential confounding. CONCLUSION: Evidence is insufficient to
      determine the effectiveness of long-term opioid therapy for improving chronic
      pain and function. Evidence supports a dose-dependent risk for serious harms.
      PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID- 25581256
TI  - Valproic acid induces neuronal cell death through a novel calpain-dependent
      necroptosis pathway.
AB  - A growing body of evidence indicates that valproic acid (VPA), a histone
      deacetylase inhibitor used to treat epilepsy and mood disorders, has histone
      deacetylase-related and -unrelated neurotoxic activity, the mechanism of which is
      still poorly understood. We report that VPA induces neuronal cell death through
      an atypical calpain-dependent necroptosis pathway that initiates with downstream
      activation of c-Jun N-terminal kinase 1 (JNK1) and increased expression of
      receptor-interacting protein 1 (RIP-1) and is accompanied by cleavage and
      mitochondrial release/nuclear translocation of apoptosis-inducing factor,
      mitochondrial release of Smac/DIABLO, and inhibition of the anti-apoptotic
      protein X-linked inhibitor of apoptosis (XIAP). Coinciding with apoptosis
      inducing factor nuclear translocation, VPA induces phosphorylation of the
      necroptosis-associated histone H2A family member H2AX, which is known to
      contribute to lethal DNA degradation. These signals are inhibited in neuronal
      cells that express constitutively activated MEK/ERK and/or PI3-K/Akt survival
      pathways, allowing them to resist VPA-induced cell death. The data indicate that
      VPA has neurotoxic activity and identify a novel calpain-dependent necroptosis
      pathway that includes JNK1 activation and RIP-1 expression. A growing body of
      evidence indicates that valproic acid (VPA) has neurotoxic activity, the
      mechanism of which is still poorly understood. We report, for the first time,
      that VPA activates a previously unrecognized calpain-dependent necroptosis
      cascade that initiates with JNK1 activation and involves AIF cleavage/nuclear
      translocation and H2AX phosphorylation as well as an altered Smac/DIABLO to XIAP
      balance. 

PMID- 25581258
TI  - Larval melanism in a geometrid moth: promoted neither by a thermal nor seasonal
      adaptation but desiccating environments.
AB  - Spatiotemporal variation in the degree of melanism is often considered in the
      context of thermal adaptation, melanism being advantageous under suboptimal
      thermal conditions. Yet, other mutually nonexclusive explanations exist. Analysis
      of geographical patterns combined with laboratory experiments on the mechanisms
      of morph induction helps to unveil the adaptive value of particular cases of
      polyphenism. In the context of the thermal melanism hypothesis and seasonal
      adaptations, we explored an array of environmental factors that may affect the
      expression and performance of nonmelanic vs. melanic larval morphs in different
      latitudinal populations of the facultatively bivoltine moth Chiasmia clathrata
      (Lepidoptera: Geometridae). Geographical variation in larval coloration was
      independent of average temperatures experienced by the populations in the wild.
      The melanic morph was, however, more abundant in dry than in mesic habitats. In
      the laboratory, the melanic morph was induced especially under a high level of
      incident radiation but also at relatively high temperatures, but independently of
      photoperiod. Melanic larvae had higher growth rates and shorter development times
      than the nonmelanic ones when both temperature and the level of incident
      radiation were high. Our results that melanism is induced and advantageous in
      warm desiccating conditions contradict the thermal melanism hypothesis for this
      species. Neither has melanism evolved to compensate time constraints due to
      forthcoming autumn. Instead, larvae solve seasonal variation in the time
      available for growth by an elevated growth rate and a shortened larval period in
      the face of autumnal photoperiods. The phenotypic response to the level of
      incident radiation and a lack of adaptive adjustment of larval growth
      trajectories in univoltine populations underpin the role of deterministic
      environmental variation in the evolution of irreversible adaptive plasticity and
      seasonal polyphenism. 

PMID- 25581260
TI  - Use of Penicillin and Streptomycin to Reduce Spread of Bacterial Coldwater
      Disease II: Efficacy of Using Antibiotics in Diluents and During Water Hardening.
AB  - Bacterial coldwater disease, caused by Flavobacterium psychrophilum, has lead to
      the loss of significant numbers of hatchery-reared salmonids. The bacteria can be
      spread from parent to progeny within contaminated sperm and ovarian fluid and can
      enter the egg during fertilization. The addition of antibiotics to diluents and
      water-hardening solutions could prevent the spread of the disease. In separate
      trials, a mixture of 0.197 mg/mL penicillin plus 0.313 mg/mL streptomycin was
      added to both a 0.5% sodium chloride fertilization diluent and hatchery well
      water during hardening. Tests showed that the addition of the antibiotics to the
      diluent and during up to 60 min of water hardening had no effect on the eye-up,
      hatch and deformity rates of Rainbow Trout Oncorhynchus mykiss eggs compared with
      the nonantibiotic-treated controls. Also, significant reductions in the
      prevalence of F. psychrophilum on the surface and inside eggs were observed when
      compared with controls. These results indicate that the addition of penicillin
      and streptomycin to diluents and during water hardening can prevent the vertical
      transmission of bacterial coldwater disease.

PMID- 25581259
TI  - Immunological potential of cytotoxic T lymphocyte antigen 4 immunoglobulin in
      murine autoimmune cholangitis.
AB  - Cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig) is an important
      regulator of T cell activation and a fusion protein directed at CD80 and CD86; it
      blocks co-stimulatory signalling and T cell activation. We have taken advantage
      of a murine model of human primary biliary cirrhosis (PBC), mice expressing a
      transforming growth factor (TGF)-beta receptor II dominant negative (dnTGF
      betaRII) transgene to address the potential therapeutic efficacy of CTLA-4 Ig. To
      mimic patients with PBC at different stages or duration of disease, we treated
      mice with either CTLA-4 Ig or control IgG three times weekly from 3 to 12 or 24
      weeks of age, or from 12 to 24 weeks of age. CTLA-4 Ig treatment from 3 weeks of
      age significantly reduced liver inflammation to 12 weeks of age. Treatment
      initiated at 12 weeks of age also ameliorated the autoimmune cholangitis at 24
      weeks of age. However, in mice treated at 3 weeks of age, suppression of liver
      inflammation was not sustained and colitis was aggravated when treatment was
      extended to 24 weeks of age. Our data indicate that, in dnTGF-betaRII mice, CTLA
      4 Ig treatment has short-term beneficial effects on autoimmune cholangitis, but
      the effect varies according to duration of treatment and the time in which
      therapy was initiated. Further dissection of the events that lead to the
      reduction in therapeutic effectiveness of CTLA-4 Ig will be critical to
      determining whether such efforts can be applied to human PBC. 

PMID- 25581262
TI  - Organic photovoltaic cells: from performance improvement to manufacturing
      processes.
AB  - Organic photovoltaics (OPVs) have been pursued as a next generation power source
      due to their light weight, thin, flexible, and simple fabrication advantages.
      Improvements in OPV efficiency have attracted great attention in the past decade.
      Because the functional layers in OPVs can be dissolved in common solvents, they
      can be manufactured by eco-friendly and scalable printing or coating
      technologies. In this review article, the focus is on recent efforts to control
      nanomorphologies of photoactive layer and discussion of various solution
      processed charge transport and extraction materials, to maximize the performance
      of OPV cells. Next, recent works on printing and coating technologies for OPVs to
      realize solution processing are reviewed. The review concludes with a discussion
      of recent advances in the development of non-traditional lamination and transfer
      method towards highly efficient and fully solution-processed OPV. 

PMID- 25581263
TI  - Altered hepatic gene expression in nonalcoholic fatty liver disease is associated
      with lower hepatic n-3 and n-6 polyunsaturated fatty acids.
AB  - In nonalcoholic fatty liver disease, hepatic gene expression and fatty acid (FA)
      composition have been reported independently, but a comprehensive gene expression
      profiling in relation to FA composition is lacking. The aim was to assess this
      relationship. In a cross-sectional study, hepatic gene expression (Illumina
      Microarray) was first compared among 20 patients with simple steatosis (SS), 19
      with nonalcoholic steatohepatitis (NASH), and 24 healthy controls. The FA
      composition in hepatic total lipids was compared between SS and NASH, and
      associations between gene expression and FAs were examined. Gene expression
      differed mainly between healthy controls and patients (SS and NASH), including
      genes related to unsaturated FA metabolism. Twenty-two genes were differentially
      expressed between NASH and SS; most of them correlated with disease severity and
      related more to cancer progression than to lipid metabolism. Biologically active
      long-chain polyunsaturated FAs (PUFAs; eicosapentaenoic acid + docosahexaenoic
      acid, arachidonic acid) in hepatic total lipids were lower in NASH than in SS.
      This may be related to overexpression of FADS1, FADS2, and PNPLA3. The degree and
      direction of correlations between PUFAs and gene expression were different among
      SS and NASH, which may suggest that low PUFA content in NASH modulates gene
      expression in a different way compared with SS or, alternatively, that gene
      expression influences PUFA content differently depending on disease severity (SS
      versus NASH). CONCLUSION: Well-defined subjects with either healthy liver, SS, or
      NASH showed distinct hepatic gene expression profiles including genes involved in
      unsaturated FA metabolism. In patients with NASH, hepatic PUFAs were lower and
      associations with gene expression were different compared to SS.

PMID- 25581261
TI  - Design, synthesis, and biological evaluation of sulfonyl acrylonitriles as novel
      inhibitors of cancer metastasis and spread.
AB  - The spread of intra-abdominal cancers is a vexing clinical problem for which
      there is no widely effective treatment. We discovered previously that (2E)-3-[(4
      tert-butylphenyl)sulfonyl]acrylonitrile (1) induced cancer cell apoptosis during
      adhesion to normal mesothelial cells which line the peritoneum. We recently
      demonstrated that the sulfonylacrylonitrile portion of 1 and hydrophobic aryl
      substitution were essential for pro-apoptotic activity in cancer cells. Here we
      synthesized a diverse series of analogues of 1 in order to improve the efficacy
      and pharmaceutical properties. Analogues and 1 were compared in their ability to
      cause cancer cell death during adhesion to normal mesothelial cell monolayers.
      Potent analogues identified in the in vitro assay were validated and found to
      exhibit improved inhibition of intra-abdominal cancer in two clinically relevant
      murine models of ovarian and pancreatic cancer spread and metastasis,
      highlighting their potential clinical use as an adjunct to surgical resection of
      cancers. 

PMID- 25581264
TI  - Characterization, Recovery Opportunities, and Valuation of Metals in Municipal
      Sludges from U.S. Wastewater Treatment Plants Nationwide.
AB  - U.S. sewage sludges were analyzed for 58 regulated and nonregulated elements by
      ICP-MS and electron microscopy to explore opportunities for removal and recovery.
      Sludge/water distribution coefficients (KD, L/kg dry weight) spanned 5 orders of
      magnitude, indicating significant metal accumulation in biosolids. Rare-earth
      elements and minor metals (Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb,
      Lu) detected in sludges showed enrichment factors (EFs) near unity, suggesting
      dust or soils as likely dominant sources. In contrast, most platinum group
      elements (i.e., Ru, Rh, Pd, Pt) showed high EF and KD values, indicating
      anthropogenic sources. Numerous metallic and metal oxide colloids (<100-500 nm
      diameter) were detected; the morphology of abundant aggregates of primary
      particles measuring <100 nm provided clues to their origin. For a community of 1
      million people, metals in biosolids were valued at up to US$13 million annually.
      A model incorporating a parameter (KD * EF * $Value) to capture the relative
      potential for economic value from biosolids revealed the identity of the 13 most
      lucrative elements (Ag, Cu, Au, P, Fe, Pd, Mn, Zn, Ir, Al, Cd, Ti, Ga, and Cr)
      with a combined value of US $280/ton of sludge.

PMID- 25581265
TI  - No conservation silver lining to Ebola.

PMID- 25581266
TI  - Differential transcriptional response to antibiotics by Pseudomonas putida DOT
      T1E.
AB  - Multi-drug resistant bacteria are a major threat to humanity, especially because
      the current battery of known antibiotics is not sufficient to combat infections
      produced by these microbes. Therefore, the study of how current antibiotics act
      and how bacteria defend themselves against antibiotics is of critical importance.
      Pseudomonas putida DOT-T1E exhibits an impressive array of RND efflux pumps,
      which confer this microorganism high resistance to organic solvents and
      antibiotics that would kill most other microorganisms. We have chosen DOT-T1E as
      a model microbe to study the microbial responses to a wide battery of antibiotics
      (chloramphenicol, rifampicin, tetracycline, ciprofloxacin, ampicillin, kanamycin,
      spectinomycin and gentamicin). Ribonucleic acid sequencing (RNA)-seq analyses
      revealed that each antibiotic provokes a unique transcriptional response profile
      in DOT-T1E. While many of the genes identified were related to known antibiotic
      targets, others were unrelated or encoded hypothetical proteins. These results
      indicate that our knowledge of antibiotic resistance mechanisms is still partial.
      We also identified 138 new small RNAs (sRNAs) in DOT-T1E, dramatically adding to
      the 16 that have been previously described. Importantly, our results reveal that
      a correlation exists between the expression of messenger RNA and sRNA, indicating
      that some of these sRNAs are likely involved in fine tuning the expression of
      antibiotic resistance genes. Taken together, these findings open new frontiers in
      the fight against multi-drug resistant bacteria and point to the potential use of
      sRNAs as novel antimicrobial targets.

PMID- 25581267
TI  - Increased expression of immuno-inhibitory molecules on peripheral blood
      lymphocytes may suppress disease progression in autoimmune hepatitis.

PMID- 25581269
TI  - Editorial comment to Efficacy of naftopidil for nocturia in male patients with
      lower urinary tract symptoms: comparison of morning and evening dosing.

PMID- 25581268
TI  - Respiratory impedance in healthy unsedated South African infants: effects of
      maternal smoking.
AB  - BACKGROUND AND OBJECTIVE: Non-invasive techniques for measuring lung mechanics in
      infants are needed for a better understanding of lung growth and function, and to
      study the effects of prenatal factors on subsequent lung growth in healthy
      infants. The forced oscillation technique requires minimal cooperation from the
      individual but has rarely been used in infants. The study aims to assess the use
      of the forced oscillation technique to measure the influence of antenatal
      exposures on respiratory mechanics in unsedated infants enrolled in a birth
      cohort study in Cape Town, South Africa. METHODS: Healthy term infants were
      studied at 6-10 weeks of age using the forced oscillation technique. Respiratory
      impedance was measured in the frequency range 8-48 Hz via a face mask during
      natural sleep. Respiratory system resistance, compliance and inertance were
      calculated from the impedance spectra. RESULTS: Of 177 infants tested, successful
      measurements were obtained in 164 (93%). Median (25-75%) values for resistance,
      compliance and inertance were 50.2 (39.5-60.6) cmH2 O.s.L(-1), 0.78 (0.61-0.99)
      mL.cmH2 O(-1) and 0.062 (0.050-0.086) cmH2 O.s(2) .L(-1), respectively. As a
      group, male infants had 16% higher resistance (P = 0.006) and 18% lower
      compliance (P = 0.02) than females. Infants whose mothers smoked during pregnancy
      had a 19% lower compliance than infants not exposed to tobacco smoke during
      pregnancy (P = 0.005). Neither maternal HIV infection nor ethnicity had a
      significant effect on respiratory mechanics. CONCLUSIONS: The forced oscillation
      technique is sensitive enough to demonstrate the effects of tobacco smoke
      exposure and sex in respiratory mechanics in healthy infants. This technique will
      facilitate assessing perinatal influences of lung function in infancy.

PMID- 25581270
TI  - Quality and safety of herbal medical products: regulation and the need for
      quality assurance along the value chains.
AB  - Herbal medicines and products derived from them are a diverse group of products
      for which different (and often limited) levels of evidence are available. As
      importantly, such products generally vary in their composition and are at the end
      of an often poorly understood value chain, which often links producers in
      biodiversity rich countries with the large markets in the North. This paper
      discusses the current regulatory framework of such herbal medical products (with
      a focus on the UK) and using examples from our own metabolomic research on
      Curcumal longa L. (turmeric, Zingiberaceae) how value chains impact on the
      composition and quality (and thus the safety) of such products. Overall, our
      recent research demonstrates the need for studying the links between producers
      and consumers of commodities produced in provider countries and that plant
      metabolomics offer a novel way of assessing the chemical variability along a
      value chain. 

PMID- 25581271
TI  - Reconstructing the ecological impacts of eight decades of mining, metallurgical,
      and municipal activities on a small boreal lake in northern Canada.
AB  - As a result of long-term metal mining and metallurgical activities, the sediment
      of Ross Lake (Flin Flon, MB, Canada) is highly contaminated with metals and other
      elements. Although the effluents likely were discharged into Ross Lake as early
      as the late 1920s, lake biophysical data were not collected until 1973, more than
      4 decades after the onset of mining and municipal activities. The early influence
      of these activities on the ecology of Ross Lake is unknown, as are the effects of
      improvements to metallurgical effluent quality and discontinuation of municipal
      wastewater discharge into the lake's north basin. To address this knowledge gap,
      analyses typical of paleolimnological investigations were applied to cores of
      sediment collected in 2009 from the south basin of Ross Lake. Stratigraphic
      analyses of physicochemical sediment characteristics (e.g., the concentrations of
      metals and other elements, organic C, total N, and delta(13)C and delta(15)N
      values) and subfossil remains (diatoms, Chironomidae, Chaoborus, and Cladocera)
      were used to infer historical biological and chemical changes in Ross Lake. With
      the onset of mining activities, concentrations of various elements (e.g., As, Cr,
      Cu, Zn, and Se) increased dramatically in the sediment profile, eventually
      declining with improved tailings management. Nevertheless, concentrations of
      metals in recent sediments remain elevated compared with pre-industrial
      sediments. Constrained cluster analyses demonstrated distinct pre-industrial and
      postindustrial communities for both the diatoms and chironomids. The biodiversity
      of the postindustrial diatom assemblages were much reduced compared with the pre
      industrial assemblages. The postindustrial chironomid assemblage was dominated by
      Chironomus and to a lesser extent by Procladius, suggesting that Ross Lake became
      a degraded environment. Abundances of Cladocera and Chaoborus were severely
      reduced in the postindustrial era, likely because of metals toxicity. Overall,
      improvements to the management of both metallurgical and municipal effluent are
      reflected in the physicochemical sediment record; nevertheless, the ecology of
      Ross Lake remains impaired and shows minimal signs of returning to a pre
      industrial state. Recommendations are made regarding possible future
      investigations at this site and the need for a framework to help assess causation
      using paleolimnological and other site data.

PMID- 25581272
TI  - Public Health System Response to Extreme Weather Events.
AB  - CONTEXT: Extreme weather events, unpredictable and often far-reaching, constitute
      a persistent challenge for public health preparedness. OBJECTIVE: The goal of
      this research is to inform public health systems improvement through examination
      of extreme weather events, comparing across cases to identify recurring patterns
      in event and response characteristics. DESIGN: Structured telephone-based
      interviews were conducted with representatives from health departments to assess
      characteristics of recent extreme weather events and agencies' responses.
      Response activities were assessed using the Centers for Disease Control and
      Prevention Public Health Emergency Preparedness Capabilities framework.
      Challenges that are typical of this response environment are reported. SETTING:
      Forty-five local health departments in 20 US states. RESULTS: Respondents
      described public health system responses to 45 events involving tornadoes,
      flooding, wildfires, winter weather, hurricanes, and other storms. Events of
      similar scale were infrequent for a majority (62%) of the communities involved;
      disruption to critical infrastructure was universal. Public Health Emergency
      Preparedness Capabilities considered most essential involved environmental health
      investigations, mass care and sheltering, surveillance and epidemiology,
      information sharing, and public information and warning. Unanticipated response
      activities or operational constraints were common. CONCLUSIONS: We characterize
      extreme weather events as a "quadruple threat" because (1) direct threats to
      population health are accompanied by damage to public health protective and
      community infrastructure, (2) event characteristics often impose novel and
      pervasive burdens on communities, (3) responses rely on critical infrastructures
      whose failure both creates new burdens and diminishes response capacity, and (4)
      their infrequency and scale further compromise response capacity. Given the
      challenges associated with extreme weather events, we suggest opportunities for
      organizational learning and preparedness improvements.

PMID- 25581273
TI  - A Review of Tools to Calculate the Cost of Health Conditions and Common Health
      Risk Factors.
AB  - A cost calculator is a software tool that calculates the monetary cost associated
      with a disease, condition, or risk factor within a population group. We attempted
      to identify all available public health cost calculators using adapted systematic
      review methodology and performed a qualitative and a quantitative review on each
      included calculator. We first abstracted each calculator to ascertain its
      subject, target user, methodology, and output. We also developed a novel set of
      scoring criteria and evaluated each calculator for transparency and
      customizability. We found a wide variety of existing calculators in terms of
      subject area, target user, and analytic methodology. Furthermore, using our
      rating criteria, we found large differences in transparency with respect to the
      assumptions and parameter inputs driving results.

PMID- 25581274
TI  - Patterns of failure in patients with head and neck carcinoma of unknown primary
      treated with radiation therapy.
AB  - BACKGROUND: The purpose of this study was to examine patterns of failure and the
      relationship to radiation doses in patients with head and neck carcinoma of
      unknown primary (HNCUP). METHODS: We reviewed 85 patients with HNCUP treated with
      curative-intent radiation therapy (RT) during 1995 to 2012. RESULTS: There have
      been no failures in the pharyngeal axis. Relapse at initial neck sites of disease
      developed in 7 patients (8.2%). The median dose to these sites was 70 Gy (range,
      63-70 Gy). Failure at neck sites without initial disease occurred in 4 patients
      (4.7%). The median dose was 54 Gy (range, 50-58.8 Gy). There were no
      contralateral failures in a small cohort of patients receiving unilateral
      treatment (n = 6). Percutaneous endoscopic gastrostomy (PEG) tube dependence at
      12 months was 7.4%, and 2.5% at 3 years. Esophageal stricture developed in 5
      patients (5.9%). CONCLUSION: RT for HNCUP produces excellent locoregional control
      rates with acceptably low levels of late toxicity. Doses prescribed to sites of
      eventual failure did not vary significantly from those sites that were treated
      and remain in control. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E426-E431,
      2016.

PMID- 25581279
TI  - Single-ended transition state finding with the growing string method.
AB  - Reaction path finding and transition state (TS) searching are important tasks in
      computational chemistry. Methods that seek to optimize an evenly distributed set
      of structures to represent a chemical reaction path are known as double-ended
      string methods. Such methods can be highly reliable because the endpoints of the
      string are fixed, which effectively lowers the dimensionality of the reaction
      path search. String methods, however, require that the reactant and product
      structures are known beforehand, which limits their ability for systematic
      exploration of reactive steps. In this article, a single-ended growing string
      method (GSM) is introduced which allows for reaction path searches starting from
      a single structure. The method works by sequentially adding nodes along
      coordinates that drive bonds, angles, and/or torsions to a desired reactive
      outcome. After the string is grown and an approximate reaction path through the
      TS is found, string optimization commences and the exact TS is located along with
      the reaction path. Fast convergence of the string is achieved through use of
      internal coordinates and eigenvector optimization schemes combined with Hessian
      estimates. Comparison to the double-ended GSM shows that single-ended method can
      be even more computationally efficient than the already rapid double-ended
      method. Examples, including transition metal reactivity and a systematic,
      automated search for unknown reactivity, demonstrate the efficacy of the new
      method. This automated reaction search is able to find 165 reaction paths from
      333 searches for the reaction of NH3 BH3 and (LiH)4 , all without guidance from
      user intuition.

PMID- 25581275
TI  - The Cocreation of Crazy Patchworks: Becoming Rhizomatic in Systemic Therapy.
AB  - In the field of systemic therapy, there has been much discussion recently about
      the narrative self. This concept refers to the idea that the self is narratively
      constructed in and through the stories which someone tells about him/herself. The
      story is thereby not only viewed as a metaphor for selfhood: Selfhood is not
      compared to a story, it is a story. But what kind of story are we talking about
      here? If the self is a story, what does that story look like? These questions are
      explored in this article. Starting from the possibilities and limitations of
      traditional and postmodern visions on the self as a story, an alternative vision
      is illustrated. By considering the self as a rhizomatic story, we not only create
      a useful view of the way narrative selfhood is constructed within a therapy
      context, but we also stimulate therapists to coconstruct-together with their
      clients-patchworks of self-stories. By using story fragments of our own practice,
      we illustrate the rhizomatic thinking and its possibilities in therapy. 

PMID- 25581280
TI  - The politics of healthcare informatics: knowledge management using an electronic
      medical record system.
AB  - The design and implementation of an electronic medical record system pose
      significant epistemological and practical complexities. Despite optimistic
      assessments of their potential contribution to the quality of care, their
      implementation has been problematic, and their actual employment in various
      clinical settings remains controversial. Little is known about how their use
      actually mediates knowing. Employing a variety of qualitative research methods,
      this article attempts an answer by illustrating how omitting, editing and
      excessive reporting were employed as part of nurses' and physicians' political
      efforts to shape knowledge production and knowledge sharing in a technologically
      mediated healthcare setting. 

PMID- 25581281
TI  - The Hippo pathway effector YAP is a critical regulator of skeletal muscle fibre
      size.
AB  - The Yes-associated protein (YAP) is a core effector of the Hippo pathway, which
      regulates proliferation and apoptosis in organ development. YAP function has been
      extensively characterized in epithelial cells and tissues, but its function in
      adult skeletal muscle remains poorly defined. Here we show that YAP positively
      regulates basal skeletal muscle mass and protein synthesis. Mechanistically, we
      show that YAP regulates muscle mass via interaction with TEAD transcription
      factors. Furthermore, YAP abundance and activity in muscles is increased
      following injury or degeneration of motor nerves, as a process to mitigate
      neurogenic muscle atrophy. Our findings highlight an essential role for YAP as a
      positive regulator of skeletal muscle size. Further investigation of
      interventions that promote YAP activity in skeletal muscle might aid the
      development of therapeutics to combat muscle wasting and neuromuscular disorders.

PMID- 25581282
TI  - Assessment of aminoglycoside dosing and estimated glomerular filtration rate in
      determining gentamicin and tobramycin area under the curve and clearance.
AB  - BACKGROUND: Aminoglycoside clearance depends on kidney function, but the
      Australian Therapeutic Guidelines for antibiotics (version 14, 2010) recommend
      initial dosing based on weight without consideration of kidney function. Other
      guidelines that modify dosing based on kidney function estimates often use the
      Cockroft-Gault equation, but the role of the estimated glomerular filtration rate
      equations for this purpose is unclear. AIM: To determine the performance of
      current guideline dosing in achieving target area-under-the-curve and examine the
      relative precision of the estimated glomerular filtration rate equations compared
      with traditional Cockroft-Gault creatinine clearance in predicting aminoglycoside
      clearance. METHODS: We analysed 496 aminoglycoside treatment episodes involving
      1377 infusions in adult patients. Conformity with antibiotic guideline dosing was
      achieved if the discrepancy between prescribed and recommended dose was less than
      15%. Aminoglycoside clearance was determined from linear regression using a one
      compartment model with the Aminoglycoside Levels and Daily Dose Indicator
      programme. We assessed the precision of the Cockroft-Gault, Modification of Diet
      in renal Disease Study and Chronic Kidney Disease-Epidemiology Collaboration (CKD
      EPI) equations in predicting aminoglycoside clearance by correlation and linear
      regression. RESULTS: Conformity with guideline dosing was not associated with
      achieving target area-under-the-curve. The CKD-EPI estimated glomerular
      filtration rate adjusted for body surface area showed the highest correlation
      (gentamicin, r = 0.66; tobramycin, r = 0.82) and best predictive model for
      aminoglycoside clearance. CONCLUSION: Current guideline dosing may be suboptimal
      for achieving target area-under-the-curve. The CKD-EPI equation adjusted for
      patient body surface area best predicts aminoglycoside clearance, and could be
      evaluated as a covariate in determining initial aminoglycoside dosing.

PMID- 25581284
TI  - Using coloured filters to reduce the symptoms of visual stress in children with
      reading delay.
AB  - BACKGROUND: Meares Irlen Syndrome (MIS), otherwise known as "visual stress", is
      one condition that can cause difficulties with reading. AIM: This study aimed to
      compare the effect of two coloured-filter systems on the symptoms of visual
      stress in children with reading delay. METHODS: The study design was a pre-test,
      post-test, randomized head-to-head comparison of two filter systems on the
      symptoms of visual stress in school children. A total of 68 UK mainstream
      schoolchildren with significant impairment in reading ability completed the
      study. RESULTS: The filter systems appeared to have a large effect on the
      reported symptoms between pre and post three-month time points (d = 2.5, r =
      0.78). Both filter types appeared to have large effects (Harris d = 1.79, r =
      0.69 and DRT d = 3.22, r = 0.85). Importantly, 35% of participants' reported that
      their symptoms had resolved completely; 72% of the 68 children appeared to gain
      improvements in three or more visual stress symptoms. CONCLUSION AND
      SIGNIFICANCE: The reduction in symptoms, which appeared to be brought about by
      the use of coloured filters, eased the visual discomfort experienced by these
      children when reading. This type of intervention therefore has the potential to
      facilitate occupational engagement.

PMID- 25581283
TI  - MARQUIS: a multiplex method for absolute quantification of peptides and
      posttranslational modifications.
AB  - Absolute quantification of protein expression and posttranslational modifications
      by mass spectrometry has been challenging due to a variety of factors, including
      the potentially large dynamic range of phosphorylation response. To address these
      issues, we have developed MARQUIS-Multiplex Absolute Regressed Quantification
      with Internal Standards-a novel mass spectrometry-based approach using a
      combination of isobaric tags and heavy-labelled standard peptides, to construct
      internal standard curves for peptides derived from key nodes in signal
      transduction networks. We applied MARQUIS to quantify phosphorylation dynamics
      within the EGFR network at multiple time points following stimulation with
      several ligands, enabling a quantitative comparison of EGFR phosphorylation sites
      and demonstrating that receptor phosphorylation is qualitatively similar but
      quantitatively distinct for each EGFR ligand tested. MARQUIS was also applied to
      quantify the effect of EGFR kinase inhibition on glioblastoma patient-derived
      xenografts. MARQUIS is a versatile method, broadly applicable and extendable to
      multiple mass spectrometric platforms. 

PMID- 25581285
TI  - Changes in characteristics and management of Asian and Anglo-Celts with type 2
      diabetes over a 15-year period in an urban Australian community: The Fremantle
      Diabetes Study.
AB  - BACKGROUND: The aim of the present study was to determine temporal changes in
      characteristics and management of Asians with type 2 diabetes (T2D) compared with
      those of the majority Anglo-Celt (AC) patients in an urban Australian community.
      METHODS: Cross-sectional data from the observational Fremantle Diabetes Study
      (FDS) collected in 1993-96 (Phase I; FDS1) and 2008-11 (Phase II; FDS2) were
      analyzed for patients classified as Asian (n = 44 and 65 in FDS1 and FDS2,
      respectively) or AC (n = 796 and 793, respectively). Between-group differences in
      changes in key variables between FDS phases were analyzed by generalized linear
      modeling with adjustment for age and gender. RESULTS: Asians patients were
      significantly younger at diagnosis and recruitment and had a lower body mass
      index and smaller waist circumference than the AC participants in both FDS
      phases. They were also less likely to be treated for hypertension. Cardiovascular
      risk factors and their management and macrovascular complications were similar in
      the two groups over time. A greater propensity to retinopathy with Asian
      ethnicity in FDS1 (27.3% vs 13.5%; P = 0.23) was attenuated in FDS2 (23.7% vs
      19.0%; P = 0.39). Asians had a significantly lower prevalence of peripheral
      sensory neuropathy in FDS2 (33.8% vs 63.3%; P < 0.001; adjusted P = 0.011 for
      between-group temporal change). CONCLUSIONS: There were persistent differences
      between the phenotypic features of Asian migrants with T2D versus AC patients in
      an Australian urban community over 15 years of follow-up, but management of
      diabetes and non-glycemic risk factors remained comparable. Ethnicity-specific
      differences in susceptibility to microvascular complications should be considered
      in clinical management.

PMID- 25581286
TI  - Editorial.

PMID- 25581287
TI  - A second look at the validity of widely used Rorschach indices: comment on
      Mihura, Meyer, Dumitrascu, and Bombel (2013).
AB  - We comment on the meta-analysis by Mihura, Meyer, Dumitrascu, and Bombel (2013),
      which examined the validity of scores in Exner's Comprehensive System (CS) for
      the Rorschach. First, we agree there is compelling evidence that 4 categories of
      cognitive scores-the "Rorschach cognitive quartet"-are related to cognitive
      ability/impairment and thought disorder. We now feel comfortable endorsing the
      use of these scores in some applied and research settings. Second, we conducted
      new meta-analyses (k = 44) for the 4 noncognitive Rorschach scores with highest
      validity in the Mihura et al. findings. Unlike Mihura et al., we included
      unpublished dissertations (although we did not attempt to exhaustively unearth
      all unpublished studies), calculated correlations instead of semipartial
      correlations, and used the Rorschach International Norms for a larger proportion
      of comparisons. Our validity estimates for the Suicide Constellation and Weighted
      Sum of Color were similar to or even higher than those of Mihura et al., although
      we concluded that support for the Suicide Constellation is limited and that
      Weighted Sum of Color probably does not measure its intended target. Our validity
      estimates for Sum Shading and the Anatomy and X-ray score were much lower than
      those of Mihura et al. We conclude that their meta-analysis accurately reflects
      the published literature, but their exclusion of unpublished studies led to
      substantial overestimates of validity for some and perhaps many Rorschach scores.
      Therefore, the evidence is presently insufficient to justify using the CS to
      measure noncognitive characteristics such as emotionality, negative affect, and
      bodily preoccupations.

PMID- 25581288
TI  - Standards, accuracy, and questions of bias in Rorschach meta-analyses: reply to
      Wood, Garb, Nezworski, Lilienfeld, and Duke (2015).
AB  - Wood, Garb, Nezworski, Lilienfeld, and Duke (2015) found our systematic review
      and meta-analyses of 65 Rorschach variables to be accurate and unbiased, and
      hence removed their previous recommendation for a moratorium on the applied use
      of the Rorschach. However, Wood et al. (2015) hypothesized that publication bias
      would exist for 4 Rorschach variables. To test this hypothesis, they replicated
      our meta-analyses for these 4 variables and added unpublished dissertations to
      the pool of articles. In the process, they used procedures that contradicted
      their standards and recommendations for sound Rorschach research, which
      consistently led to significantly lower effect sizes. In reviewing their meta
      analyses, we found numerous methodological errors, data errors, and omitted
      studies. In contrast to their strict requirements for interrater reliability in
      the Rorschach meta-analyses of other researchers, they did not report interrater
      reliability for any of their coding and classification decisions. In addition,
      many of their conclusions were based on a narrative review of individual studies
      and post hoc analyses rather than their meta-analytic findings. Finally, we
      challenge their sole use of dissertations to test publication bias because (a)
      they failed to reconcile their conclusion that publication bias was present with
      the analyses we conducted showing its absence, and (b) we found numerous problems
      with dissertation study quality. In short, one cannot rely on the findings or the
      conclusions reported in Wood et al.

PMID- 25581290
TI  - Correlates of psychological distress immediately following colposcopy.
AB  - OBJECTIVE: Women are at risk for prolonged psychological distress following
      attendance at colposcopy for cervical abnormalities, with potentially negative
      consequences. Little is presently known about the correlates of post-colposcopy
      distress. The present study aimed to extend knowledge of correlates of post
      colposcopy anxiety and negative affect, and identify women at risk for elevated
      psychological distress. METHODS: Psychosocial data (demographic variables,
      anxiety, negative affect, and pain) were collected using validated questionnaires
      from 164 women attending colposcopy for the first time immediately prior to their
      colposcopy examination and immediately following it. Two separate logistic
      regressions were conducted to identify key factors that may be useful targets for
      preventing post-colposcopy distress and to determine which factors exert the
      biggest influence and therefore may be targeted in future intervention studies.
      RESULTS: Pre-colposcopy state anxiety, pain experienced during colposcopy, and
      trait anxiety emerged as independent predictors of post-colposcopy state anxiety,
      accounting for 36% of the variance. Pre-colposcopy negative affect, pain
      experienced during colposcopy, trait anxiety, and referral smear grade were
      independent predictors of post-colposcopy negative affect, explaining 32% of
      variance. CONCLUSIONS: Whether or not women underwent punch biopsy or treatment
      did not influence post-colposcopy distress levels; however, pain experienced
      during colposcopy remains a risk for continued psychological distress. Trait
      anxiety may be an important variable to consider in future studies, as women high
      in trait anxiety may represent a particularly vulnerable subgroup of women
      referred for colposcopy, at greater risk for negative psychosocial consequences
      associated with colposcopy, and to be targeted for interventions to reduce
      psychological distress.

PMID- 25581289
TI  - Detection of viruses by counting single fluorescent genetically biotinylated
      reporter immunophage using a lateral flow assay.
AB  - We demonstrated a lateral flow immunoassay (LFA) for detection of viruses using
      fluorescently labeled M13 bacteriophage as reporters and single-reporter counting
      as the readout. AviTag-biotinylated M13 phage were functionalized with antibodies
      using avidin-biotin conjugation and fluorescently labeled with AlexaFluor 555.
      Individual phage bound to target viruses (here MS2 as a model) captured on an LFA
      membrane strip were imaged using epi-fluorescence microscopy. Using automated
      image processing, we counted the number of bound phage in micrographs as a
      function of target concentration. The resultant assay was more sensitive than
      enzyme-linked immunosorbent assays and traditional colloidal-gold nanoparticle
      LFAs for direct detection of viruses. 

PMID- 25581292
TI  - Estimation of the quality of refined protein crystal structures.
AB  - Crystallographic R work and R free values, which are measures of the ability of
      the models of macromolecular structures to explain the crystallographic data on
      which they are based, are often used to assess structure quality. It is widely
      known, and confirmed here that both are sensitive to the methods used to compute
      them, and can be manipulated to improve the apparent quality of the model. As an
      alternative it is proposed here that the quality of crystallographic models
      should be assessed using a global goodness-of-fit metric RO2A /R work where RO2A
      is the number of reflections used for refinement divided by the number of
      nonhydrogen atoms in the structure, and R work is the working R-factor of the
      refined structure. Also, analysis of structures in the Protein Data Bank suggests
      that many data sets have been truncated at high resolution, thereby improving the
      R-factor statistics. To discourage this practice, it is proposed that the
      resolution of a dataset be defined as the resolution of the shell of data where
      <I/sigmaI > falls to 1. The proposed goodness-of-fit metric encourages
      investigators to use all the data available rather than a truncated subset.

PMID- 25581291
TI  - A Bioecological framework to evaluate communicative participation outcomes for
      preschoolers receiving speech-language therapy interventions in Ontario, Canada.
AB  - BACKGROUND: The Preschool Speech and Language Program (PSLP) in Ontario, Canada,
      is a publically funded intervention service for children from birth to 5 years
      with communication disorders. It has begun a population-level programme
      evaluation of children's communicative participation outcomes following therapy.
      Data are currently being collected for all children who access this service--over
      50,000 children each year. AIMS: To understand and evaluate how therapeutic
      interventions in speech-language therapy impact the everyday lives of children
      and families by applying a theoretical framework. MAIN CONTRIBUTION: This
      discussion paper critically examines how the Bioecological Model of Development
      can be applied to the study of communicative participation outcomes following
      speech and language therapy. This model will be used in future analyses of
      communicative participation outcomes data in Ontario's PSLP. The strengths and
      challenges of this approach are reviewed.

PMID- 25581294
TI  - Male reproductive system of the fish ectoparasite Argulus bengalensis (Crustacea:
      Branchiura).
AB  - The male reproductive system of the fish ectoparasite Argulus bengalensis was
      reconstructed with serial histological sections through longitudinal and
      transverse planes and the description was re-evaluated after the discovery of
      spermatophore. The study revealed that the testis of A. bengalensis consists of
      two lobes, each comprised the two enclaves. The outer enclaves from both lobes
      are connected proximally with an isthmus. The inner enclave is covered with two
      layers of chromatophores which are presumably involved in androgenic hormone
      production. At the proximal end of the inner enclaves a pair of vasa efferentia
      originates and ascends into thorax where it leads into vesicula seminalis. Like
      Dolops ranarum, a pair of spermatophoric glands is found in the thorax just
      behind the second maxilla. Glandular cells of the spermatophoric glands are
      columnar with a large nucleus at their basal side. A pair of spermatophoric
      canals carries the secretion of the glands into the vesicula seminalis through
      vasa efferentia. Spermatophores are delivered to the female through a median vas
      deference originating from the vesicula seminalis. In addition to the
      spermatophoric glands, a pair of accessory glands is located in the coxa of the
      fourth thoracic legs. At the region dorsal to the isthmus both the spermatophoric
      canal and accessory gland ducts unite with the vas efferens of the respective
      side. The secretion of the accessory gland presumably contributes to semen
      composition of the parasite.

PMID- 25581293
TI  - Tuning the buffering capacity of polyethylenimine with glycerol molecules for
      efficient gene delivery: staying in or out of the endosomes.
AB  - Endosomal escape is a major bottleneck for efficient non-viral gene delivery.
      This paper presents the development of two novel non-viral vectors by cross
      linking glycerol molecules with low molecular weight polyethylenimine (PEI). The
      vectors, namely, HG-PEI (45 mol% glycerol content) and LG-PEI (9 mol% glycerol
      content) have apparently similar DNA binding, DNA unpacking and cellular uptake
      abilities but differ in buffering capacity. The cellular uptake and subsequent
      transfection efficiency of LG-PEI is superior to commercially available PEI 25 k.
      Interestingly, although the cellular uptake of HG-PEI is higher than that of PEI
      25 k, the transgene expression by HG-PEI-mediated transfection is very low.
      Inhibitor and co-localization studies demonstrate the mechanism of endocytosis
      and formation of endosomes prone to lysosomal lysis of HG-PEI polyplexes as a
      consequence of its weak buffering capacity. Importantly, when the lysosomal lysis
      is inhibited, the transgene expression of HG-PEI-mediated transfection increases
      by 9-fold of its initial capacity which is comparable to the transfection
      efficiency of PEI 25 k. These results indicated that the buffering capacity of
      the polymers primarily impacts endosomal escape and subsequent transfection
      efficiency. Furthermore, this study highlights the significance of cross-linkers
      in optimizing the buffering capacity when designing polymers for gene delivery. 

PMID- 25581295
TI  - Atomic layer deposition of metal sulfide materials.
AB  - CONSPECTUS: The field of nanoscience is delivering increasingly intricate yet
      elegant geometric structures incorporating an ever-expanding palette of
      materials. Atomic layer deposition (ALD) is a powerful driver of this field,
      providing exceptionally conformal coatings spanning the periodic table and atomic
      scale precision independent of substrate geometry. This versatility is intrinsic
      to ALD and results from sequential and self-limiting surface reactions. This
      characteristic facilitates digital synthesis, in which the film grows linearly
      with the number of reaction cycles. While the majority of ALD processes
      identified to date produce metal oxides, novel applications in areas such as
      energy storage, catalysis, and nanophotonics are motivating interest in sulfide
      materials. Recent progress in ALD of sulfides has expanded the diversity of
      accessible materials as well as a more complete understanding of the unique
      chalcogenide surface chemistry. ALD of sulfide materials typically uses
      metalorganic precursors and hydrogen sulfide (H2S). As in oxide ALD, the
      precursor chemistry is critical to controlling both the film growth and
      properties including roughness, crystallinity, and impurity levels. By
      modification of the precursor sequence, multicomponent sulfides have been
      deposited, although challenges remain because of the higher propensity for cation
      exchange reactions, greater diffusion rates, and unintentional annealing of this
      more labile class of materials. A deeper understanding of these surface chemical
      reactions has been achieved through a combination of in situ studies and quantum
      chemical calculations. As this understanding matures, so does our ability to
      deterministically tailor film properties to new applications and more
      sophisticated devices. This Account highlights the attributes of ALD chemistry
      that are unique to metal sulfides and surveys recent applications of these
      materials in photovoltaics, energy storage, and photonics. Within each
      application space, the benefits and challenges of novel ALD processes are
      emphasized and common trends are summarized. We conclude with a perspective on
      potential future directions for metal chalcogenide ALD as well as untapped
      opportunities. Finally, we consider challenges that must be addressed prior to
      implementing ALD metal sulfides into future device architectures.

PMID- 25581296
TI  - Experiences of sleep and benzodiazepine use among older women.
AB  - Sleep disturbances are common among older women; however, little is known about
      sleep experiences among chronic benzodiazepine users. The experience of sleep,
      sleep troubles, and management of sleep problems were explored through
      semistructured interviews with 12 women aged 65-92 who had used a benzodiazepine
      for three months or longer to treat a sleep disturbance. Themes that emerged from
      an interpretive phenomenological analysis included multiple reasons for sleep
      disruptions (health problems, mental disturbances, and sleeping arrangements),
      opposing effects of benzodiazepines on sleep (helps or does not work), and
      several supplemental sleep strategies (modification of the environment,
      distraction, and consumption). 

PMID- 25581297
TI  - Health-related quality of life may improve after transplantation in pancreas
      kidney recipients.
AB  - Pancreas-kidney transplantation (PKT) may significantly improve quality of life
      (HRQOL) in patients with type 1 diabetes. We have assessed the changes felt by
      PKT patients, using the Gastrointestinal Quality of Life Index (GIQLI) and
      EuroQol-5D questionnaires. Patients were asked to compare how their HRQOL had
      changed from pre-transplantation to the last visit. The 60 men and 66 women
      enrolled had a mean follow-up of five yr; 84.1% with both grafts, 15.9% with one
      graft functioning. In all domains of EuroQol-5D scores improved after PKT, as
      well as the visual analogue scale health state (from 38% to 84%, p < 0.001;
      effect size 3.34). In GIQLI, physical function was felt better after PKT than
      before (14.83 +/- 3.86 vs. 7.86 +/- 4.43, p < 0.001; effect size 1.68); the same
      was observed for psychological status, social function, and GI complaints.
      Concerning the burden of medical treatment, the score significantly improved
      (from 1.31 to 3.63, p < 0.001, effect size 2.02). The rate of unemployed patients
      decreased after PKT (from 50.8% to 36.5%, p < 0.001). Multivariate analysis
      showed that having only one functioning graft was associated with worse HRQOL
      scores (B = -5.157, p = 0.015). In conclusion, for all assessed domains, patients
      reported a significant improvement in HRQOL after PKT. Maintenance of the two
      grafts functioning predicted higher improvement of HRQOL scores.

PMID- 25581299
TI  - Myenteric plexitis at the proximal resection margin is a predictive marker for
      surgical recurrence of ileocaecal Crohn's disease.
AB  - AIM: Identifying predictors for the recurrence of Crohn's disease (CD) after
      surgery to improve disease surveillance or targeted therapy is rational. The
      purpose of this study was to examine the relationship between myenteric plexitis
      (MP) and clinical or surgical recurrence. METHOD: Between 2000 and 2010, patients
      who underwent primary ileocaecal resection for CD at a single tertiary referral
      centre were identified. The histopathology was retrospectively reviewed for MP at
      the resection margins. The severity of MP was graded from 0 to 3 using a
      previously described classification. Information on demographics, surgical
      details and evidence of clinical or surgical recurrence was obtained from medical
      records. RESULTS: There were 86 patients (49 women) of median age 31.5
      (interquartile ratio 23.5-41.0) years. Seventy-six and 77 specimens were
      assessable for proximal and distal MP. Proximal MP was present in 53 (69.7%)
      patients and was classified as mild, moderate or severe in 30 (39.5%), 14 (18.4)
      and nine (11.8%). MP at the distal resection margin was present in 40 (51.9%).
      Forty (46.5%) patients developed clinical recurrence of whom 16 (18.6%) required
      surgery. Clinical factors that predicted recurrence included age > 40 (P = 0.001)
      and the presence of an anastomosis (P = 0.023). On univariate analysis severe
      plexitis (Grade 3 MP) was also associated with surgical recurrence (P = 0.035).
      CONCLUSION: This retrospective study supports the association between MP at the
      proximal resection margin and surgical recurrence.

PMID- 25581298
TI  - Selection of subspecialty fellows in anesthesia for pediatric anesthesia: a
      national survey of program directors in the United States.
AB  - BACKGROUND: Several studies have investigated the selection process for medical
      students, residents, and fellows across different specialties. Currently, the
      selection criteria used by pediatric anesthesia program directors to select
      prospective pediatric anesthesia fellows are unknown. OBJECTIVE: To evaluate the
      criteria used by program directors in the selection of prospective pediatric
      anesthesia fellows in the United States. METHODS: Survey responses were solicited
      from 51 pediatric anesthesia fellowship directors in the United States. Questions
      evaluated department demographic information, the importance of fellowship
      selection criteria, and program satisfaction with the Match process. RESULTS:
      Forty-two of 51 fellowship directors responded to the survey (a response rate of
      82%). The personal statement was reported as extremely/very important for 30 of
      42 (71%) program directors, while research experience and prior publications were
      reported as extremely/very important for 16 of 41 (39%) and 16 of 41 (39%)
      program directors, respectively. Programs that offered all the spots through the
      Match were smaller, median (IQR) number of fellows of 3 (2-6) compared to the
      ones that did not offer all the spots through the Match, 8 (2-12), P = 0.03. In
      contrast, no difference in program directors' satisfaction with the Match was
      detected between smaller (<= 3 fellows) and larger programs (>3 fellows), P =
      0.25. CONCLUSION: A minority of pediatric fellowship program directors rated
      prior research experience as an important factor in the selection of prospective
      fellows. The lack of emphasis on research qualities for fellows is potentially
      concerning for the future of our specialty.

PMID- 25581300
TI  - Malondialdehyde, superoxide dismutase and melatonin levels in gingival crevicular
      fluid of aggressive and chronic periodontitis patients.
AB  - BACKGROUND: The aim of this study was to investigate malondialdehyde (MDA),
      superoxide dismutase (SOD) and melatonin levels in the gingival crevicular fluid
      (GCF) of patients with chronic periodontitis (CP) and generalized aggressive
      periodontitis (GAgP) as biomarkers for oxidative stress. METHODS: The study
      comprised 65 subjects: 15 healthy individuals, 25 CP patients and 25 GAgP
      patients. Plaque index, gingival index, pocket depth, clinical attachment level
      measurements and GCF samples were obtained from all subjects. MDA, SOD and
      melatonin levels were determined utilizing enzyme-linked immunosorbent assay.
      RESULTS: GCF-MDA levels were significantly higher in the GAgP group compared to
      the CP and control groups (p < 0.001) and significantly higher in the CP group
      than the C group (p < 0.001). SOD and melatonin GCF levels were significantly
      higher in the control than the GAgP and CP groups (p < 0.05), and significantly
      lower in the GAgP than the CP group (p < 0.05). The CP group demonstrated a
      significant negative correlation between GCF-MDA and melatonin concentrations. A
      positive correlation was observed between SOD and CAL in the CP group and PD in
      the GAgP group. CONCLUSIONS: MDA, melatonin and SOD could be considered as
      biomarkers for oxidative stress in periodontal diseases and might be useful
      diagnostic aids in distinguishing CP and GAgP patients.

PMID- 25581301
TI  - Surface coating of pancreatic islets with neural crest stem cells improves
      engraftment and function after intraportal transplantation.
AB  - The present study aimed to develop techniques for surface coating of islets with
      neural crest stem cells (NCSCs) in order to enable cotransplantation to the
      clinically used liver site and then investigate engraftment and function
      intraportally of such bioengineered islets. Mouse islets were coated during
      incubation with enhanced green fluorescent protein (EGFP)-expressing mouse NCSCs
      and transplanted into the portal vein to cure diabetic mice. An intravenous
      glucose tolerance test was performed at 1 month posttransplantation. Islet grafts
      were retrieved and evaluated for vascular density, nerves, and glial cells. NCSCs
      expressed a vast number of key angiogenic and neurotrophic factors. Mice
      transplanted with NCSC-bioengineered islets responded better to the glucose load
      than recipient mice with control islets. NCSCs remained present in the vicinity
      or had often migrated into the NCSC-coated islets, and an improved islet graft
      reinnervation and revascularization was observed. Transplanted NCSCs
      differentiated into both glial and neural cells in the islet grafts. We conclude
      that bioengineering of islets with NCSCs for intraportal transplantation provides
      a possibility to improve islet engraftment and function. Pending successful
      establishment of protocols for expansion of NCSCs from, for example, human skin
      or bone marrow, this strategy may be applied to clinical islet transplantation. 

PMID- 25581302
TI  - Outer-inner membrane vesicles naturally secreted by gram-negative pathogenic
      bacteria.
AB  - Outer-inner membrane vesicles (O-IMVs) were recently described as a new type of
      membrane vesicle secreted by the Antarctic bacterium Shewanella vesiculosa M7T.
      Their formation is characterized by the protrusion of both outer and plasma
      membranes, which pulls cytoplasmic components into the vesicles. To demonstrate
      that this is not a singular phenomenon in a bacterium occurring in an extreme
      environment, the identification of O-IMVs in pathogenic bacteria was undertaken.
      With this aim, a structural study by Transmission Electron Microscopy (TEM) and
      Cryo-transmission electron microscopy (Cryo-TEM) was carried out, confirming that
      O-IMVs are also secreted by Gram-negative pathogenic bacteria such as Neisseria
      gonorrhoeae, Pseudomonas aeruginosa PAO1 and Acinetobacter baumannii AB41, in
      which they represent between 0.23% and 1.2% of total vesicles produced. DNA and
      ATP, which are components solely found in the cell cytoplasm, were identified
      within membrane vesicles of these strains. The presence of DNA inside the O-IMVs
      produced by N. gonorrhoeae was confirmed by gold DNA immunolabeling with a
      specific monoclonal IgM against double-stranded DNA. A proteomic analysis of N.
      gonorrhoeae-derived membrane vesicles identified proteins from the cytoplasm and
      plasma membrane. This confirmation of O-IMV extends the hitherto uniform
      definition of membrane vesicles in Gram-negative bacteria and explains the
      presence of components in membrane vesicles such as DNA, cytoplasmic and inner
      membrane proteins, as well as ATP, detected for the first time. The production of
      these O-IMVs by pathogenic Gram-negative bacteria opens up new areas of study
      related to their involvement in lateral gene transfer, the transfer of
      cytoplasmic proteins, as well as the functionality and role of ATP detected in
      these new vesicles. 

PMID- 25581303
TI  - A new algorithm to reduce inappropriate therapy in the S-ICD system.
AB  - INTRODUCTION: The subcutaneous ICD system (S-ICD) has been shown to be a safe and
      effective treatment for patients at risk for sudden cardiac death. This device
      reliably detects ventricular tachyarrhythmias with a low incidence of
      inappropriate shocks for supraventricular arrhythmias. However, T-wave
      oversensing (TWOS) is more common with the S-ICD compared with transvenous
      systems. We developed a novel discrimination algorithm to reduce TWOS without
      compromising tachyarrhythmia discrimination. METHODS AND RESULTS: The algorithm
      was developed using a database of recorded episodes, including 244 appropriate
      therapies for ventricular arrhythmias and 133 episodes with an inappropriate
      detection due to TWOS, and using a computer model that simulates the S-ICD
      system. An independent set of data of 161 TWOS episodes, 137 ventricular and 328
      supraventricular episodes, was used to validate the algorithm on actual device
      hardware. The S-ICD performance with the new algorithm was compared with the S
      ICD without the new algorithm. Development results showed a decrease in
      inappropriate charge due to TWOS by 30.7 +/- 18%. All ventricular arrhythmias
      were appropriately detected and the time to appropriate charge initiation was not
      increased. System validation showed that the new algorithm avoided an
      inappropriate charge due to TWOS by 39.8 +/- 11.4%. No decrease in ventricular
      arrhythmia sensitivity and no significant change in supraventricular specificity
      were observed. CONCLUSIONS: A new algorithm that uses correlation of the existing
      complex to previous complexes reduced TWOS episodes by approximately 40%. The
      algorithm has potential for a clinically meaningful decrease in inappropriate
      shocks.

PMID- 25581304
TI  - Endovascular repair of a 63-year-old complication: post-traumatic anterior tibial
      artery arteriovenous fistula.

PMID- 25581306
TI  - Pain Assessment with Short Message Service and Interactive Voice Response in
      Outpatients with Cancer and Pain: A Feasibility Study.
AB  - BACKGROUND: Pain assessment and monitoring is a prerequisite for its adequate
      treatment in patients with cancer. We performed a feasibility study on the use of
      short message service (SMS) and interactive voice response (IVR) to improve pain
      management in patients with cancer, including terminally ill patients. METHODS:
      During 4 weeks, palliative patients received a daily IVR asking to provide their
      pain score on a numeric rating scale (NRS) with their mobile phone. If pain was
      moderate or high, the nurse contacted the patient the same day and, if required,
      adapted the treatment. RESULTS: Thirteen of the 17 invited patients agreed to
      participate (79%), four died during the study period. IVR/SMS provides a reliable
      assessment of the pain intensity, and if required, treatment can be rapidly
      adapted. All patients were satisfied with the intervention. There were no
      difficulties for the, mainly older, patients in handling this communication way
      on pain intensity. The mean pain score decreased from 4.78 to 3.33 (P = 0.07).
      The pain scale of the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire (EORTC QLQ-C30) decreased significantly from 56 to
      35 (P = 0.047). DISCUSSION: Monitoring and managing pain with IVR/SMS in patients
      with cancer at home appeared acceptable and feasible, even in terminally ill
      patients. The reluctance for actively contacting the professional in case of
      increased pain intensity is circumvented in this setting. Further research,
      preferably in a controlled study, is needed to establish the use of this
      intervention in a larger patient population.

PMID- 25581305
TI  - Effects of the kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) on
      cocaine versus food choice and extended-access cocaine intake in rhesus monkeys.
AB  - The dynorphin/kappa opioid receptor (KOR) system has been implicated as one
      potential neurobiological modulator of the abuse-related effects of cocaine and
      as a potential target for medications development. This study determined effects
      of the KOR antagonist nor-binaltorphimine (nor-BNI) on cocaine self
      administration under a novel procedure that featured two daily components: (1) a
      2-hour 'choice' component (9:00-11:00 am) when monkeys could choose between food
      pellets and cocaine injections (0-0.1 mg/kg per injection, intravenous) and (2) a
      20-hour 'extended-access' component (noon to 8:00 am) when cocaine (0.1 mg/kg per
      injection) was available under a fixed-ratio schedule to promote high daily
      cocaine intakes. Rhesus monkeys (n = 4) were given 14 days of exposure to the
      choice + extended-access procedure then treated with nor-BNI (3.2 or 10.0 mg/kg,
      intramuscular), and cocaine choice and extended-access cocaine intake were
      evaluated for an additional 14 days. Consistent with previous studies, cocaine
      maintained both a dose-dependent increase in cocaine choice during choice
      components and a high level of cocaine intake during extended-access components.
      Neither 3.2 nor 10 mg/kg nor-BNI significantly altered cocaine choice or extended
      access cocaine intake. In two additional monkeys, nor-BNI also had no effect on
      cocaine choice or extended-access cocaine intake when it was administered at the
      beginning of exposure to the extended-access components. Overall, these results
      do not support a major role for the dynorphin/KOR system in modulating cocaine
      self-administration under these conditions in non-human primates nor do they
      support the clinical utility of KOR antagonists as a pharmacotherapeutic strategy
      for cocaine addiction.

PMID- 25581307
TI  - First trimester contingent testing with either nuchal translucency or cell-free
      DNA. Cost efficiency and the role of ultrasound dating.
AB  - OBJECTIVE: To evaluate the performance and cost efficacy of different first
      trimester contingent screening strategies based on an initial analysis of
      biochemical markers. DESIGN: Retrospective study. SETTING: Swedish National
      Quality Register for prenatal diagnosis. POPULATION: 35,780 women with singleton
      pregnancies. METHODS: Serum values from first trimester biochemistry were re
      analyzed in a contingent approach. For risks between 1:40 and 1:1000, risk
      estimates from nuchal translucency measurements were added and outcomes were
      compared using either a final cut-off risk of 1:200 to proceed with invasive
      testing or offering non-invasive prenatal testing. In a subgroup of 12,836 women
      with regular menstrual cycles the same analyses were performed using data on the
      last menstrual period for determining gestational age. The costs of detecting one
      case of aneuploidy were compared. MAIN OUTCOME MEASURES: Comparison of screening
      strategies. RESULTS: The detection rate was the same (87%) in the contingent
      group as in complete combined screening, with only 41% requiring a nuchal
      translucency scan. As an alternative, offering non-invasive prenatal testing to
      the intermediate risk group would result in a detection rate of 98%, but the cost
      to detect one case of trisomy 21 would be 83% higher than the cost associated
      with traditional combined screening. CONCLUSIONS: First trimester examination
      using a contingent approach will achieve similar results compared with full
      combined screening. Non-invasive prenatal testing will not be cost-effective when
      a high proportion of pregnancies need further testing.

PMID- 25581308
TI  - Remembrance of immunology past: conversations with Herman Eisen.
AB  - Herman Eisen and Sondra Schlesinger spent several days together in September 2007
      in Woods Hole, Massachusetts, talking about immunology, focusing on his
      remembrances of the field over the more than 60 years of his involvement. This
      article is an abridged version of those discussions (the full version is
      available on the Annual Reviews website). It is both an oral history and a
      written memory of some important but selected areas of immunology. 

PMID- 25581312
TI  - Falls and fractures with atypical antipsychotic medication use: a population
      based cohort study.

PMID- 25581311
TI  - Calcitonin physiology, saved by a lysophospholipid.

PMID- 25581314
TI  - Side-chain-bulk effects on the molecular packing and photovoltaic performance of
      benzotrithiophene-benzooxadiazole conjugated copolymers.
AB  - Two alternating donor-acceptor conjugated polymers, PBTTBO-C13 C11 and PBTTBO-C13
      C8 , comprising 5-alkylbenzo[1,2-b:3,4-b':5,6-d'']trithiophene (BTT) as the donor
      and 4,7-bis(4-dodecylthien-2-yl)benzo[1,2,5]oxadiazole (BO) as the acceptor, with
      different alkyl side-chain architectures on their BTT units are synthesized, and
      their bulk heterojunction photovoltaic properties when blended with the fullerene
      PC71 BM are characterized. Even a slight change in the length of the alkyl chain
      of the BTT units influences the steric bulk to such a degree that it
      substantially affects the molecular packing of the polymers and the performance
      of their photovoltaic devices. The bulkier side chains of the polymer PBTTBO-C13
      C11 not only prevent its crystallization, but also suppress its light-absorption
      coefficient relative to that of PBTTBO-C13 C8 , as evidenced by X-ray diffraction
      and UV/Vis absorption studies, presumably because of weakened intermolecular
      interactions. Moreover, the polymer bearing bulkier side chains, PBTTBO-C13 C11 ,
      is less miscible with PC71 BM than PBTTBO-C13 C8 , and this characteristic
      determines the morphology of their annealed blended films, as shown by TEM
      studies. The best efficiency is obtained with a device containing an annealed
      PBTTBO-C13 C8 /PC71 BM (1/2 w/w) active layer that was maintained at 120  degrees
      C for 10 min, which shows a power conversion efficiency of 6.2 %, an open-circuit
      voltage of 0.75 V, a short-circuit current density of 12.6 mA cm(-2) , and a fill
      factor of 66 %. 

PMID- 25581313
TI  - Six-month outcomes in dental patients identified with hyperglycaemia: a
      randomized clinical trial.
AB  - AIM: To assess an approach to improving behavioural and glycaemic outcomes in
      dental patients who present with diabetes risk factors and previously
      unrecognized hyperglycaemia. METHODS: We randomized 101 individuals identified
      with potential diabetes or pre-diabetes into two interventions. In the
      basic/control intervention, participants were informed about their diabetes risk
      factors and blood test result, and advised to see a physician. In the
      enhanced/test intervention, patients received a detailed explanation of findings
      and their implications, a written report for the physician, and were contacted at
      2 and 4 months to inquire whether medical follow-up had occurred. At a 6-month re
      evaluation, outcome measures included visit to physician, positive lifestyle
      changes and reduction in HbA1c. RESULTS: Seventy-three subjects returned for the
      6-month visit. The two intervention groups did not significantly differ in any of
      the outcome variables. Eighty-four percent of subjects reported having visited a
      physician post-randomization, and 49% reported at least one positive lifestyle
      change as a result of our intervention. In subjects identified with potential
      diabetes (baseline HbA1c >= 6.5%), HbA1c was reduced 1.46 +/- 0.28% compared to
      baseline (p < 0.01). CONCLUSION: Diabetes risk assessment and education by dental
      professionals of affected individuals unaware of their status may contribute to
      improved patient outcomes.

PMID- 25581315
TI  - Post-Ike economic resilience along the Texas coast.
AB  - The economic devastation resulting from recent natural disasters has spawned
      intense interest in programmes that promote regional resilience. The economic
      impacts of Hurricane Ike (September 2008) endured long beyond the storm's
      landfall, compounded by a national recession. This study analyses the pattern of
      post-Ike industrial growth in eight coastal counties of Texas, United States, and
      identifies sources of resilience and potential drivers of recovery. The results
      indicate that post-disaster growth patterns differ from established growth
      patterns. Levels of resilience vary across industrial sectors, and service
      sectors tend to lead a recovery. The resilience of the hotel and restaurant
      sector, for instance, suggests that the presence of relief workers might immunise
      certain sectors against a post-disaster economic downturn. Besides the sectors
      that are generally resilient, each county has its own distinct sectors that,
      depending on the extent of the damage suffered, tend to perform strongly after a
      disaster, owing to the characteristics of the respective county's economy. 

PMID- 25581309
TI  - Innate immune pattern recognition: a cell biological perspective.
AB  - Receptors of the innate immune system detect conserved determinants of microbial
      and viral origin. Activation of these receptors initiates signaling events that
      culminate in an effective immune response. Recently, the view that innate immune
      signaling events rely on and operate within a complex cellular infrastructure has
      become an important framework for understanding the regulation of innate
      immunity. Compartmentalization within this infrastructure provides the cell with
      the ability to assign spatial information to microbial detection and regulate
      immune responses. Several cell biological processes play a role in the regulation
      of innate signaling responses; at the same time, innate signaling can engage
      cellular processes as a form of defense or to promote immunological memory. In
      this review, we highlight these aspects of cell biology in pattern-recognition
      receptor signaling by focusing on signals that originate from the cell surface,
      from endosomal compartments, and from within the cytosol. 

PMID- 25581316
TI  - Crop yield response to climate change varies with cropping intensity.
AB  - Projections of the response of crop yield to climate change at different spatial
      scales are known to vary. However, understanding of the causes of systematic
      differences across scale is limited. Here, we hypothesize that heterogeneous
      cropping intensity is one source of scale dependency. Analysis of observed global
      data and regional crop modelling demonstrate that areas of high vs. low cropping
      intensity can have systematically different yields, in both observations and
      simulations. Analysis of global crop data suggests that heterogeneity in cropping
      intensity is a likely source of scale dependency for a number of crops across the
      globe. Further crop modelling and a meta-analysis of projected tropical maize
      yields are used to assess the implications for climate change assessments. The
      results show that scale dependency is a potential source of systematic bias. We
      conclude that spatially comprehensive assessments of climate impacts based on
      yield alone, without accounting for cropping intensity, are prone to systematic
      overestimation of climate impacts. The findings therefore suggest a need for
      greater attention to crop suitability and land use change when assessing the
      impacts of climate change. 

PMID- 25581317
TI  - Co-Planting Cd Contaminated Field Using Hyperaccumulator Solanum Nigrum L.
      Through Interplant with Low Accumulation Welsh Onion.
AB  - Monoculture and intercrop of hyperaccumulator Solanum nigrum L. with low
      accumulation Welsh onion Renbentieganchongwang were conducted. The results showed
      that the remove ratio of S. nigrum to Cd was about 7% in intercrop plot when top
      soil (0-20 cm) Cd concentration was 0.45-0.62 mg kg(-1), which did not
      significantly impact the yield of low accumulation Welsh onion compared to the
      monoculture. The consistency of remove ratio in practice and theory indicated the
      remediation of S. nigrum to Cd was significant. The Cd concentration and yield of
      Welsh onion were not affected by the growth of S. nigrum either in intercrop
      plot. The Cd concentration in edible parts of Welsh onion was available either.
      In short, inter-planting hyperaccumulator with low accumulation crop could
      normally remediate contaminated soil and produce crop (obtain economic benefit),
      which may be one practical pathway of phytoremediating heavy metal contaminated
      soil in the future.

PMID- 25581318
TI  - Hybrid organic/inorganic thin-film multijunction solar cells exceeding 11% power
      conversion efficiency.
AB  - Hybrid multijunction solar cells comprising hydrogenated amorphous silicon and an
      organic bulk heterojunction are presented, reaching 11.7% power conversion
      efficiency. The benefits of merging inorganic and organic subcells are pointed
      out, the optimization of the cells, including optical modeling predictions and
      tuning of the recombination contact are described, and an outlook of this
      technique is given. 

PMID- 25581310
TI  - Microbiota-mediated inflammation and antimicrobial defense in the intestine.
AB  - The diverse microbial populations constituting the intestinal microbiota promote
      immune development and differentiation, but because of their complex metabolic
      requirements and the consequent difficulty culturing them, they remained, until
      recently, largely uncharacterized and mysterious. In the last decade, deep
      nucleic acid sequencing platforms, new computational and bioinformatics tools,
      and full-genome characterization of several hundred commensal bacterial species
      facilitated studies of the microbiota and revealed that differences in microbiota
      composition can be associated with inflammatory, metabolic, and infectious
      diseases, that each human is colonized by a distinct bacterial flora, and that
      the microbiota can be manipulated to reduce and even cure some diseases.
      Different bacterial species induce distinct immune cell populations that can play
      pro- and anti-inflammatory roles, and thus the composition of the microbiota
      determines, in part, the level of resistance to infection and susceptibility to
      inflammatory diseases. This review summarizes recent work characterizing
      commensal microbes that contribute to the antimicrobial defense/inflammation
      axis. 

PMID- 25581319
TI  - A highly resilient mesoporous SiOx lithium storage material engineered by oil
      water templating.
AB  - Mesoporous silicon-based materials gained considerable attention as high-capacity
      lithium-storage materials. However, the practical use is still limited by the
      complexity and limited number of available synthetic routes. Here, we report
      carbon-coated porous SiOx as high capacity lithium storage material prepared by
      using a sol-gel reaction of hydrogen silsesquioxane and oil-water templating. A
      hydrophobic oil is employed as a pore former inside the SiOx matrix and a
      precursor for carbon coating on the SiOx . The anode exhibits a high capacity of
      730 mAh g(-1) and outstanding cycling performance over 100 cycles without
      significant dimensional changes. Carbon-coated porous SiOx also showed highly
      stable thermal reliability comparable to that of graphite. These promising
      properties come from the mesopores in the SiOx matrix, which ensures reliable
      operation of lithium storage in SiOx . The scalable sol-gel process presented
      here can open up a new avenue for the versatile preparation of porous SiOx
      lithium storage materials. 

PMID- 25581320
TI  - Quantitative assay for the colonization ability of heterogeneous bacteria on
      controlled nanopillar structures.
AB  - The colonization ability of bacteria on biomaterial surfaces is influenced by the
      morphology of the bacteria and the nanotopography of the biomaterial. However,
      interactions between the bacterial morphology and nanotopography of biomaterials
      have not yet been completely elucidated. In this article, we quantitatively
      characterized the bacterial morphology to illuminate the integrated effects of
      polyethylene terephthalate (PET) nanopillar arrays on the colonization of
      bacteria cells with different shapes. Our results demonstrated that the
      interaction between interpillar spacing and the diameter of the bacterial cells
      impacted the number of bacterial cells that adhered to different PET substrates.
      The interpillar spacing of nanopillar arrays promotes bacterial adhesion in a
      definite range (<50 nm). However, further increasing the interpillar spacing
      inhibited the adhesion of bacteria to the nanopillar arrays. Moreover, the
      interpillar spacing also influenced the morphologies of adherent bacterial cells
      on the PET nanopillar arrays, which consequently facilitated bacterial adhesion
      to the nanopillar arrays. Our findings enhance the understanding of interactions
      between controlled nanotopography and bacterial colonization and provide an
      appropriate parameter for the design of antibacterial materials with
      nanotopography. 

PMID- 25581321
TI  - Semiconducting single crystals comprising segregated arrays of complexes of C60.
AB  - Although pristine C60 prefers to adopt a face-centered cubic packing arrangement
      in the solid state, it has been demonstrated that noncovalent-bonding
      interactions with a variety of molecular receptors lead to the complexation of
      C60 molecules, albeit usually with little or no control over their long-range
      order. Herein, an extended viologen-based cyclophane-ExBox2(4+)-has been employed
      as a molecular receptor which, not only binds C60 one-on-one, but also results in
      the columnar self-assembly of the 1:1 inclusion complexes under ambient
      conditions. These one-dimensional arrays of fullerenes stack along the long axis
      of needle-like single crystals as a consequence of multiple noncovalent-bonding
      interactions between each of the inclusion complexes. The electrical conductivity
      of these crystals is on the order of 10(-7) S cm(-1), even without any evacuation
      of oxygen, and matches the conductivity of high-quality, unfunctionalized C60
      based materials that typically require stringent high-temperature vaporization
      techniques, along with the careful removal of oxygen and moisture, prior to
      measuring their conductance.

PMID- 25581322
TI  - Physicochemical characterization of cyclodextrin-drug interactions in the solid
      state and the effect of water on these interactions.
AB  - The characterization of cyclodextrin (CD)-drug interactions has encountered
      difficulties in the solid state, especially of amorphous state. However, recent
      advances in experimental techniques, such as X-ray diffraction, spectroscopy,
      thermal analysis, and solid-state nuclear magnetic resonance, as well as
      computational chemistry have provided new insights in this area. Furthermore,
      inclusion complexes have been found to originate from noncovalent interactions,
      such as van der Waals and hydrogen bonding. The formation of CD hydrates and
      inclusion complexes in the solid state is considered to only rely on
      intermolecular interactions, without any covalent bond rupture and formation in
      host and guest molecules. The presence of water molecules as special guests
      impacts on the solid-state arrangement of CD molecules, which makes this
      influence important to consider. Accordingly, this review presents an overview of
      recent work about the physicochemical characterization of CD-drug interactions in
      the solid state with a focus on the effect of water molecules on these
      interactions.

PMID- 25581323
TI  - Impact of lower concentrations of phytoestrogens on the effects of estradiol in
      breast cancer cells.
AB  - OBJECTIVE: To explore the impact of lower concentrations of phytoestrogens on
      17beta-estradiol (E2) in the growth of MCF-7 breast cells. METHODS: MCF-7 cells
      were treated with E2 (10(-8) mol/l), one of three phytoestrogens (genistein,
      resveratrol, and quercetin) (10(-7)  to 10(-5) mol/l), and with a combination of
      both E2 and one of these phytoestrogens for 48 h. These cells were then extracted
      for MTT and TUNEL assay. Western blot was utilized to evaluate the proteins
      involved in the proliferative and apoptotic pathways, as well as the differential
      effects on ERalpha and beta. RESULTS: MCF-7 cell proliferations were induced by
      both E2 alone and E2 plus one of the three phytoestrogens (at concentrations >=
      10(-6) mol/l). Apoptotic cells were significantly increased in the phytoestrogen
      treated MCF-7 cells and, conversely, suppressed in the cells treated with both E2
      and phytoestrogens. Proliferating cell nuclear antigen, PI3K and p-Akt were
      increased in the cultures with E2 and substantially more in the cultures with E2
      plus a phytoestrogen. The combination of E2 and phytoestrogen significantly
      inhibited the increase in FADD, cytochrome C, truncated Bid, caspase-9, caspase-3
      and ERbeta that was induced by phytoestrogens in the MCF-7. ERalpha expression
      was significantly induced by E2 regardless of the presence of these
      phytoestrogens. CONCLUSIONS: This study demonstrates that, in the presence of E2,
      genistein, resveratrol, and quercetin may stimulate breast cancer cells, even at
      low physiological concentrations. Therefore, the conflicting results regarding
      the effects of phytoestrogens on breast cells may be attributed to the endogenous
      estrogen present in breast tissue.

PMID- 25581325
TI  - How to select the spermatozoon for intracytoplasmic sperm injection in 2015?
AB  - The selection of the individual spermatozoon in intracytoplasmic sperm injection
      (ICSI) is routinely performed by the observation of its motility and morphology.
      However, in case of severe oligoasthenozoospermia or non-obstructive azoospermia
      requiring the use of testicular sperm, other methods are necessary to help the
      embryologist making this choice. According to some authors, sperm processing
      before ICSI seems to limit the DNA fragmentation index, and in this way improves
      ICSI outcomes. Moreover, intracytoplasmic morphologically selected sperm
      injection is potentially a good option in some specific indications such as
      severe teratozoospermia, or repeated ICSI failures. Other methods based on sperm
      structure, as sperm head birefringence observation, or based on its function,
      like the hyaluronic acid or zona pellucida binding capacity, could be of
      interest, but still need to be evaluated. Finally, in case of akinetozoospermia,
      the use of functional tests, such as pentoxifylline test, HOS-test, or to a
      lesser extent laser touch, makes the selection of viable spermatozoa easier.
      Nevertheless, studies on larger series have to be conducted to evaluate and
      precise the interest of each of these methods and their indications, before
      considering an application on larger scale. 

PMID- 25581324
TI  - A pocket guide to identify patients at risk for chronic kidney disease after
      liver transplantation.
AB  - Chronic kidney disease (CKD) after liver transplantation (LT) has a strong impact
      on transplant and patient survival. After LT, a significant proportion of
      patients develop renal dysfunction with a high risk to progress to end-stage
      renal disease (ESRD). Because of the multifactorial nature of CKD in the post
      transplant period, the ability to accurately identify patients at risk and the
      development of preventative strategies remain unsolved issues. In some patients,
      the pretransplant kidney function significantly declines within the first year
      post-LT. Until now, no user-friendly and reliable prediction scores exist to
      identify these patients early on. Data from 328 consecutive adult patients
      receiving their first LT between 2004 and 2008 at Hannover Medical School were
      analyzed to develop a prediction model using ordinal logistic regression. We
      developed a concise risk score identifying the five most important predictors and
      performed a temporal validation using a prospectively monitored patient cohort of
      120 patients from our transplant center. Based on those five parameters, we
      developed a pocket guide card for clinical use that could be a useful tool for
      instant identification of patients at high risk as well as patients more suitable
      for combined liver and kidney transplantation (CLKT). 

PMID- 25581327
TI  - Tuning the reorganization energy of electron transfer in supramolecular ensembles
      -metalloporphyrin, oligophenylenevinylenes, and fullerene--and the impact on
      electron transfer kinetics.
AB  - Oligo(p-phenylenevinylene) (oPPV) wires of various lengths featuring pyridyls at
      one terminal and C60 moieties at the other, have been used as molecular building
      blocks in combination with porphyrins to construct a novel class of electron
      donor-acceptor architectures. These architectures, which are based on non
      covalent, directional interactions between the zinc centers of the porphyrins and
      the pyridyls, have been characterized by nuclear magnetic resonance spectroscopy
      and mass spectrometry. Complementary physico-chemical assays focused on the
      interactions between electron donors and acceptors in the ground and excited
      states. No appreciable electron interactions were noted in the ground state,
      which was being probed by electrochemistry, absorption spectroscopy, etc.; the
      electron acceptors are sufficiently decoupled from the electron donors. In the
      excited state, a different picture evolved. In particular, steady-state and time
      resolved fluorescence and transient absorption measurements revealed substantial
      electron donor-acceptor interactions. These led, upon photoexcitation of the
      porphyrins, to tunable intramolecular electron-transfer processes, that is, the
      oxidation of porphyrin and the reduction of C60. In this regard, the largest
      impact stems from a rather strong distance dependence of the total reorganization
      energy in stark contrast to the distance independence seen for covalently linked
      conjugates. 

PMID- 25581329
TI  - Exploring antioxidants.

PMID- 25581328
TI  - Sleepiness at the wheel across Europe: a survey of 19 countries.
AB  - The European Sleep Research Society aimed to estimate the prevalence,
      determinants and consequences of falling asleep at the wheel. In total, 12 434
      questionnaires were obtained from 19 countries using an anonymous online
      questionnaire that collected demographic and sleep-related data, driving
      behaviour, history of drowsy driving and accidents. Associations were quantified
      using multivariate logistic regression. The average prevalence of falling asleep
      at the wheel in the previous 2 years was 17%. Among respondents who fell asleep,
      the median prevalence of sleep-related accidents was 7.0% (13.2% involved
      hospital care and 3.6% caused fatalities). The most frequently perceived reasons
      for falling asleep at the wheel were poor sleep in the previous night (42.5%) and
      poor sleeping habits in general (34.1%). Falling asleep was more frequent in the
      Netherlands [odds ratio = 3.55 (95% confidence interval: 1.97; 6.39)] and Austria
      [2.34 (1.75; 3.13)], followed by Belgium [1.52 (1.28; 1.81)], Portugal [1.34
      (1.13, 1.58)], Poland [1.22 (1.06; 1.40)] and France [1.20 (1.05; 1.38)]. Lower
      odds were found in Croatia [0.36 (0.21; 0.61)], Slovenia [0.62 (0.43; 0.89)] and
      Italy [0.65 (0.53; 0.79)]. Individual determinants of falling asleep were younger
      age; male gender [1.79 (1.61; 2.00)]; driving >=20 000 km year [2.02 (1.74;
      2.35)]; higher daytime sleepiness [7.49 (6.26; 8.95)] and high risk of
      obstructive sleep apnea syndrome [3.48 (2.78; 4.36) in men]. This Pan European
      survey demonstrates that drowsy driving is a major safety hazard throughout
      Europe. It emphasizes the importance of joint research and policy efforts to
      reduce the burden of sleepiness at the wheel for European drivers.

PMID- 25581330
TI  - Synthesis, optical properties, and electronic structures of nucleobase-containing
      pi-conjugated oligomers.
AB  - The molecular recognition properties of the nucleobases instruct the formation of
      complex three-dimensional architectures in natural and synthetic systems;
      relatively unexplored is their use as building blocks for pi-conjugated materials
      where they might mutually tune electronic and supramolecular structures. Toward
      this goal, an introductory set (1a-d and 2a-d) of six purine-terminated and two
      pyrimidine-terminated pi-conjugated oligomers has been synthesized and used to
      develop experimental electronic and photophysical structure-property trends.
      Unlike 2,2':5',2"-terthiophene (TTT) derivatives 2a-d, intramolecular charge
      transfer dominates oligomers 1a-d bearing a 4,7-bisthienylbenzothiadiazole (TBT)
      spacer due to the strong electron-accepting ability of its benzothiadiazole (BTD)
      ring. The resulting donor-acceptor-donor systems feature lower HOMO-LUMO gaps
      than the terthiophene-linked nucleobases (DeltaE(g) ~ 1.8 eV vs 2.4 eV based on
      electrochemical measurements), and the lowest so far for pi-conjugated molecules
      that include nucleobases within the pi-framework. Experiments reveal a dependence
      of photophysical and electronic structure on the nature of the nucleobase and are
      in good agreement with theoretical calculations performed at the B3LYP/6-31+G**
      level. Overall, the results show how nucleobase heterocycles can be installed
      within pi-systems to tune optical and electronic properties. Future work will
      evaluate the consequences of these information-rich components on supramolecular
      pi-conjugated structure.

PMID- 25581331
TI  - A yolk-like multifunctional platform for multimodal imaging and synergistic
      therapy triggered by a single near-infrared light.
AB  - To integrate photodynamic therapy (PDT) with photothermal therapy (PTT) and
      chemotherapy for enhanced antitumor efficiency, we developed a mild and rational
      route to synthesize novel multifunctional GdOF:Ln@SiO2 (Ln = 10%Yb/1%Er/4%Mn)
      mesoporous capsules using strong up-conversion luminescent (UCL) GdOF:Ln as cores
      and mesoporous silica layer as shells, followed by modification with varied
      functional groups onto the framework. It was found that due to the codoped
      Yb/Er/Mn in GdOF, the markedly enhanced red emission can efficiently transfer
      energy to the conjugated PDT agent (ZnPc) which produces high singlet oxygen, and
      the incorporated carbon dots outside the shell can generate obvious thermal
      effect under 980 nm laser irradiation and also prevent the premature leaking of
      ZnPc. Simultaneously, the as-produced thermal effect can obviously enhance the
      doxorubicin (DOX) release, which greatly improves the chemotherapy, resulting in
      a synergistic therapeutic effect. The system exhibits drastically enhanced
      therapeutic efficiency against tumor growth, as demonstrated both in vitro and in
      vivo. Especially, the doped rare earth ions in the host endow the material with
      excellent UCL imaging, magnetic resonance imaging (MRI), and computed tomography
      (CT) imaging properties, thus realizing the target of multimodal imaging guided
      multiple therapies. 

PMID- 25581332
TI  - Evaluation of a postdischarge coronary artery disease management program.
AB  - OBJECTIVES: We conducted a demonstration project to assess the value of a nurse
      practitioner (NP) based coronary artery disease management (CAD-DM) program for
      patients with an acute coronary syndrome (ACS) or percutaneous coronary
      intervention. METHODS: Patients were recruited to attend three 1-h monthly
      visits. The intervention included assessment of clinical symptoms and guideline
      based treatments; education regarding CAD/ACS; review of nutrition, exercise, and
      appropriate referrals; and recognition of significant symptoms and emergency
      response. RESULTS: Two hundred thirteen (84.5%) completed the program. Physician
      approval for patient participation was 99%. Average age was 63 +/- 11 years, 70%
      were male, and 89% white. At baseline, 61% (n = 133) had one or more
      cardiopulmonary symptoms, which declined to 30% at 12 weeks, p < .001. Sixty-nine
      percent attended cardiac rehabilitation or an exercise consult. Compared to the
      initial assessment, an additional 20% were at low-density lipoprotein cholesterol
      < 70 mg/dL (p = .04), an additional 35% met exercise goals (p < .0001), and there
      was an improvement in the mental (baseline 49.7 vs. 12 weeks 53, p = .0015) and
      physical components (44 vs. 48, p = .002) of the SF-12 health survey. CONCLUSION:
      This NP-based CAD-DM program was well received and participants demonstrated
      improvement in physical and mental health, and increased compliance with
      recommended lifestyle changes.

PMID- 25581333
TI  - Vibrational relaxation and energy migration of N-methylacetamide in water: the
      role of nonbonded interactions.
AB  - Nonequilibrium molecular dynamics (MD) simulations together with physics-based
      force fields are used to follow energy flow between vibrationally excited N
      methylacetamide (NMA) and water. The simulations are carried out with a
      previously validated force field for NMA, based on a multipolar representation of
      the electrostatics, and with a new fluctuating point charge model. For the water
      solvent, a flexible and a rigid model was employed to distinguish between the
      role of inter- and intramolecular degrees of freedom. On a 10 ps time scale about
      90% of the available energy goes into the solvent. The remaining energy resides
      within internal NMA-degrees of freedom from where energy flow takes place on
      longer time scales. The total amount of energy transferred to the solvent on the
      10 ps time scale does not depend on whether the water molecules are rigid or
      flexible during the simulations. Vibrational energy relaxation time scales
      include two regimes: one on the several 100 fs time scale and a longer one,
      ranging from 6 to 10 ps. This longer time scale agrees with previous simulations
      but overestimates the experimentally determined relaxation time by a factor of 2,
      which can be explained by the classical treatment of the vibrations. Including a
      previously determined quantum correction factor brings the long time scale into
      quite favorable agreement with experiment. Coupling to the bending vibration of
      the water molecules in H-bonding contact with the excited C?O chromophore is
      substantial. The equilibrium and nonequilibrium distribution of the bending
      angles of the water molecules in contact with the local oscillator are non
      Gaussian, and one approaches the other on the subpicosecond time scale. Analysis
      of the water velocity distribution suggests that the C?O vibrational energy
      relaxes into the solvent water shells in an impulsive fashion on a picosecond
      time scale. 

PMID- 25581334
TI  - Symptom-association probability between meal ingestion and abdominal pain in
      patients with irritable bowel syndrome. Does somatization play a role?
AB  - BACKGROUND: Patients with irritable bowel syndrome (IBS) complain of postprandial
      abdominal pain, but it is still unknown how much of this association is due to
      chance. Somatization enhances the perception of symptoms after a meal. We
      assessed: (i) the proportion of meal-related pain periods and the symptom
      association probability (SAP) between the two variables in IBS patients; and (ii)
      how this association is affected by somatization. METHODS: Seventy IBS patients
      recorded the times of meals and abdominal pain in a 10-day diary card. The
      proportion of postmeal pain periods was calculated in relation to the total
      number of 90-min periods with pain. Fisher's exact test was used to calculate the
      probability (p) of an association within a time window of 90 min, and the SAP was
      calculated as (1 - p) * 100%. The IBS Symptom Severity Scale, the SCL90-R for
      psychological symptoms, and the SF-36 for the quality of life were completed. KEY
      RESULTS: The proportion of postmeal pain periods was 42 +/- 27%. SAP was
      significant (p < 0.05) in 32 patients (45%). Somatization was altered in 30
      patients (47%), who were younger and had more severe IBS and a poorer quality of
      life. Somatization did not influence the association between meal ingestion and
      abdominal pain. CONCLUSIONS & INFERENCES: Meal ingestion and abdominal pain are
      significantly associated in 45% of IBS patients. Somatization influences IBS
      severity and the patients' quality of life, but not the strength of the
      association between eating and pain.

PMID- 25581335
TI  - Use of penicillin and streptomycin to reduce spread of bacterial coldwater
      disease I: antibiotics in sperm extenders.
AB  - Bacterial coldwater disease caused by Flavobacterium psychrophilum has led to the
      loss of significant numbers of hatchery-reared salmonids. The bacteria can be
      spread from parent to progeny within contaminated sperm and ovarian fluid.
      Methods for disinfecting ovarian fluid and unfertilized eggs are available, but
      methods for disinfecting sperm have not been described. In this study we
      determined whether sperm extenders containing a mixture of penicillin and
      streptomycin can be used to eliminate F. psychrophilum. In vitro trials
      demonstrated that when Rainbow Trout Oncorhynchus mykiss sperm is mixed with an
      extender, a 15-min exposure to 0.197 mg penicillin plus 0.313 mg/mL streptomycin
      is effective at killing the bacteria and has no effect on sperm motility. Small
      scale trials showed that egg fertilization rates were not reduced when sperm held
      in an extender solution containing the same antibiotic mixture for 15 min was
      used to fertilize eggs. Production-scale trials, however, showed a roughly 18%
      decrease in egg fertilization rate when sperm stored in an antibiotic containing
      extender was used. To determine why a reduction in fertilization capacity was
      observed, a small-scale experiment testing the fertilization of eggs with larger
      quantities of sperm was performed and showed that increasing the volume of sperm
      used did not increase fertilization rates. Our results demonstrate that extenders
      containing penicillin and streptomycin can be used to disinfect sperm, especially
      when small quantities of eggs are fertilized, but factors negatively affecting
      egg fertilization and survival on a production scale still need further
      investigation.

PMID- 25581336
TI  - Association of killer cell immunoglobulin-like receptor and human leucocyte
      antigen-Cw gene combinations with systemic lupus erythematosus.
AB  - Killer cell immunoglobulin-like receptors (KIRs) are a diverse family of
      activating and inhibitory receptors expressed on natural killer (NK) cells and T
      cells, the genes of which show extreme polymorphism. Some KIRs bind to human
      leucocyte antigen (HLA) class I subgroups, and genetic interactions between KIR
      genes and their ligand HLA have been shown to be associated with several
      autoimmune diseases. The present study aimed to investigate whether the
      combinations of KIR genes and HLA-Cw ligands associate with the susceptibility of
      systemic lupus erythematosus (SLE). Polymerase chain reaction using sequence
      specific primers was used to determine the genotypes of KIR genes and HLA-Cw
      alleles. We found that the frequencies of HLA-Cw07 were statistically
      significantly higher in the patient group than those in the control group (P =
      0.009). KIR2DS1(+) HLA(-) Cw(Lys) was more common in subjects with SLE compared
      to control subjects (P = 0.015). In addition, the frequency of KIR2DS1 was
      increased in SLE when KIR2DL1/HLA-Cw are absent, and the difference was
      significant (P = 0.001). KIR genotype and HLA ligand interaction may potentially
      influence the threshold for NK (and/or T) cell activation mediated through
      activating receptors, thereby contributing to the pathogenesis of SLE. 

PMID- 25581337
TI  - The cytochrome P450 2D-mediated formation of serotonin from 5-methoxytryptamine
      in the brain in vivo: a microdialysis study.
AB  - The cytochrome P450 2D (CYP2D) mediates synthesis of serotonin from 5
      methoxytryptamine (5-MT), shown in vitro for cDNA-expressed CYP2D-isoforms and
      liver and brain microsomes. We aimed to demonstrate this synthesis in the brain
      in vivo. We measured serotonin tissue content in brain regions after 5-MT
      injection into the raphe nuclei (Model-A), and its extracellular concentration in
      rat frontal cortex and striatum using an in vivo microdialysis (Model-B) in male
      Wistar rats. Naive rats served as control animals. 5-MT injection into the raphe
      nuclei of PCPA-(tryptophan hydroxylase inhibitor)-pretreated rats increased the
      tissue concentration of serotonin (from 40 to 90% of the control value,
      respectively, in the striatum), while the CYP2D inhibitor quinine diminished
      serotonin level in some brain structures of those animals (Model-A). 5-MT given
      locally through a microdialysis probe markedly increased extracellular serotonin
      concentration in the frontal cortex and striatum (to 800 and 1000% of the basal
      level, respectively) and changed dopamine concentration (Model-B). Quinine alone
      had no effect on serotonin concentration; however, given jointly with 5-MT, it
      prevented the 5-MT-induced increase in cortical serotonin in naive rats and in
      striatal serotonin in PCPA-treated animals. These results indicate that the CYP2D
      catalyzed alternative pathway of serotonin synthesis from 5-MT is relevant in the
      brain in vivo, and set a new target for the action of psychotropics.

PMID- 25581338
TI  - Self-assembling hydrogels crosslinked solely by receptor-ligand interactions:
      tunability, rationalization of physical properties, and 3D cell culture.
AB  - We report a novel, noncovalent hydrogel system crosslinked solely by receptor
      ligand interactions between biotin and avidin. The simple hydrogel synthesis and
      functionalization together with the widespread use of biotinylated ligands in
      biosciences make this versatile system suitable for many applications. The gels
      possess a range of tunable physical properties, including stiffness, lifetime,
      and swelling. The erosion rates, unexpectedly fast compared to the kinetic
      parameters for biotin-avidin, are explored in terms of stretching tensions on the
      polymers, a concept well-known on the single-molecule level, but largely
      unexplored in supramolecular systems. As proof of utility, the gels were
      functionalized with different peptide sequences to control human mesenchymal
      stromal cell morphology in 3D culture. 

PMID- 25581339
TI  - Development of multinational definitions of minimal clinically important
      improvement and patient acceptable symptomatic state in osteoarthritis.
AB  - OBJECTIVE: The ability to interpret scores from patient-reported outcome measures
      at the individual patient level depends on the availability of valid, clinically
      meaningful benchmarks of response and state attainment. The goal was to develop
      multinational estimates for minimal clinically important improvement (MCII) and
      patient acceptable symptomatic state (PASS). METHODS: A multinational sample of
      patients with osteoarthritis (OA) was evaluated before and 4 weeks after
      treatment with nonsteroidal antiinflammatory drugs. Patients completed either the
      Western Ontario and McMaster Osteoarthritis Index (WOMAC) numerical rating scale
      3.1 (hip and knee OA) or the Australian/Canadian Index (AUSCAN) numerical rating
      scale 3.1 (hand OA) before and after treatment. Patients rated the clinical
      importance of their response to treatment and their satisfaction with the health
      state achieved, from which multinational MCII and PASS estimates were calculated
      for both the WOMAC and AUSCAN indices. RESULTS: A total of 609 patients from 7
      countries participated in the study. MCII and PASS estimates varied slightly by
      instrument and subscale. Absolute (percentage) change for MCII ranged 6-9 (10% to
      17%) for WOMAC and 4-9 (8% to 15%) for AUSCAN. PASS estimates ranged 39-48 for
      WOMAC and 38-45 for AUSCAN. Some between-country variation was observed in MCII
      and PASS. CONCLUSION: Preliminary multinational estimates for MCII and PASS have
      been developed for several countries. Further research is required to evaluate
      the robustness, temporal consistency, and age- and sex-dependency of the
      preliminary estimates as well as their generalizability to other countries,
      languages, cultures, regions, and other condition-specific outcome measures.

PMID- 25581340
TI  - Seed growth of tungsten diselenide nanotubes from tungsten oxides.
AB  - We report growth of tungsten diselenide (WSe2) nanotubes by chemical vapor
      deposition with a two-zone furnace. WO3 nanowires were first grown by annealing
      tungsten thin films under argon ambient. WSe2 nanotubes were then grown at the
      tips of WO3 nanowires through selenization via two steps: (i) formation of
      tubular WSe2 structures on the outside of WO3 nanowires, resulting in core (WO3)
      shell (WSe2) and (ii) growth of WSe2 nanotubes at the tips of WO3 nanowires. The
      observed seed growth is markedly different from existing substitutional growth of
      WSe2 nanotubes, where oxygen atoms are replaced by selenium atoms in WO3
      nanowires to form WSe2 nanotubes. Another advantage of our growth is that WSe2
      film was grown by simply supplying hydrogen gas, where the native oxides were
      reduced to thin film instead of forming oxide nanowires. Our findings will
      contribute to engineer other transition metal dichacogenide growth such as MoS2,
      WS2, and MoSe2.

PMID- 25581341
TI  - National Institutes of Health Pathways to Prevention Workshop: the role of
      opioids in the treatment of chronic pain.
AB  - This National Institutes of Health (NIH) Pathways to Prevention Workshop was
      cosponsored by the NIH Office of Disease Prevention (ODP), the NIH Pain
      Consortium, the National Institute on Drug Abuse, and the National Institute of
      Neurological Disorders and Stroke. A multidisciplinary working group developed
      the workshop agenda, and an evidence-based practice center prepared an evidence
      report through a contract with the Agency for Healthcare Research and Quality to
      facilitate the workshop discussion. During the 1.5-day workshop, invited experts
      discussed the body of evidence, and attendees had opportunities to provide
      comments during open discussion periods. After weighing evidence from the
      evidence report, expert presentations, and public comments, an unbiased,
      independent panel prepared a draft report that identified research gaps and
      future research priorities. The report was posted on the ODP Web site for 2 weeks
      for public comment. This article is an abridged version of the panel's full
      report, which is available at https://prevention.nih.gov/programs-events/pathways
      to-prevention/workshops/opioids-chronic-pain/workshop-resources#final report. 

PMID- 25581342
TI  - Outlier robust nonlinear mixed model estimation.
AB  - In standard analyses of data well-modeled by a nonlinear mixed model, an aberrant
      observation, either within a cluster, or an entire cluster itself, can greatly
      distort parameter estimates and subsequent standard errors. Consequently,
      inferences about the parameters are misleading. This paper proposes an outlier
      robust method based on linearization to estimate fixed effects parameters and
      variance components in the nonlinear mixed model. An example is given using the
      four-parameter logistic model and bioassay data, comparing the robust parameter
      estimates with the nonrobust estimates given by SAS((r)).

PMID- 25581344
TI  - Composition and biological activities of slaughterhouse blood from red deer,
      sheep, pig and cattle.
AB  - BACKGROUND: Animal blood is a large-volume by-product of the meat industry.
      Besides blood meal fertiliser, blood is marketed for human consumption as a
      supplement. Minimal comparative work on slaughterhouse animal blood fractions has
      been carried out. In this study, slaughterhouse deer, sheep, pig and cattle blood
      parameters were compared. Some blood constituents were determined. Fractionated
      blood was assessed for antioxidant activity (2,2-diphenyl-1-picrylhydrazyl
      radical scavenging, oxygen radical scavenging capacity and ferric reducing
      antioxidant power). Angiotensin converting enzyme (ACE) inhibitory activity and
      antimicrobial activity were also assessed. RESULTS: Serum iron ranged from 35.3
      +/- 0.6 umol L(-1) in cattle to 16.3 +/- 3.1 umol L(-1) in deer. Cattle had the
      highest total plasma proteins (81.7 +/- 1.5 g L(-1)). While the plasma fractions
      contained considerable antioxidant activity, the red blood cell fractions of all
      four animal species contained higher antioxidant activity (P < 0.05). Negligible
      levels of ACE inhibitory activity were found for all animal blood fractions.
      Antimicrobial activity was detected towards Escherichia coli, Staphylococcus
      aureus and Pseudomonas aeruginosa with sheep white blood cells from which a crude
      neutrophil extract was obtained which demonstrated concentration-dependent
      inhibitory effects on the growth rates of these bacterial strains. CONCLUSION:
      Fractionated animal blood obtained from local slaughterhouses contains native
      proteins that possess antioxidant activity and antimicrobial activity.

PMID- 25581343
TI  - White matter microstructure and developmental improvement of
      hyperactive/impulsive symptoms in attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: A developmental improvement of symptoms in attention
      deficit/hyperactivity disorder (ADHD) is frequently reported, but the underlying
      neurobiological substrate has not been identified. The aim of this study was to
      determine whether white matter microstructure is related to developmental
      improvement of ADHD symptoms. METHODS: A cross-sectional magnetic resonance
      imaging (MRI) analysis was embedded in a prospective follow-up of an adolescent
      cohort of ADHD and control subjects (NeuroIMAGE). Mean age at baseline was 11.9
      years, mean interval of follow-up was 5.9 years. About 75.3% of the original
      cohort was retained successfully. Data of 101 participants with ADHD combined
      type at baseline and 40 healthy controls were analysed. ADHD symptoms were
      measured with semistructured, investigator-based interviews and Conners'
      questionnaires, on the basis of DSM-IV criteria. Fractional anisotropy (FA) and
      mean diffusivity (MD) indices of white matter microstructure were measured using
      whole brain diffusion tensor imaging at follow-up only. In a dimensional analysis
      FA and MD were related to change in ADHD symptoms. To link this analysis to DSM
      IV diagnoses, a post hoc categorical group analysis was conducted comparing
      participants with persistent (n = 59) versus remittent (n = 42) ADHD and
      controls. RESULTS: Over time, participants with ADHD showed improvement mainly in
      hyperactive/impulsive symptoms. This improvement was associated with lower FA and
      higher MD values in the left corticospinal tract at follow-up. Findings of the
      dimensional and the categorical analysis strongly converged. Changes in
      inattentive symptoms over time were minimal and not related to white matter
      microstructure. CONCLUSIONS: The corticospinal tract is important in the control
      of voluntary movements, suggesting the importance of the motor system in the
      persistence of hyperactive/impulsive symptoms.

PMID- 25581345
TI  - Dual antitumor and antiangiogenic activity of organoplatinum(II) complexes.
AB  - A library of over 20 cycloplatinated compounds of the type [Pt(dmba-R)LCl] (dmba
      R = C,N-dimethylbenzylamine-like ligand; R being MeO, Me, H, Br, F, CF3, and NO2
      substituents in the R5 or R4 position of the phenyl ring; L = DMSO and P(C6H4CF3
      p)3) has been prepared. All compounds are active in both human ovarian carcinoma
      A2780 cells and cisplatin-resistant A2780cisR cells, with most of the DMSO
      platinum complexes exhibiting IC50 values in the submicromolar range in the A2780
      cell line. Interestingly, DMSO platinum complexes show low cytotoxicity in the
      nontumorigenic kidney cell line BGM and therefore high selectivity factors SF. In
      addition, some of the DMSO platinum complexes effectively inhibit angiogenesis in
      the human umbilical vein endothelial cell line EA.hy926. These are the first
      platinum(II) complexes reported to inhibit angiogenesis at a close concentration
      to their IC50 in A2780 cells, turning them into dual cytotoxic and antiangiogenic
      compounds. 

PMID- 25581346
TI  - Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when
      complexed with a cell-penetrating peptide or combined with CpG.
AB  - Recognition of pathogen-derived nucleic acids by immune cells is critical for the
      activation of protective innate immune responses. Bacterial cyclic dinucleotides
      (CDNs) are small nucleic acids that are directly recognized by the cytosolic DNA
      sensor STING (stimulator of IFN genes), initiating a response characterized by
      proinflammatory cytokine and type I IFN production. Strategies to improve the
      immune stimulatory activities of CDNs can further their potential for clinical
      development. Here, we demonstrate that a simple complex of cylic-di-GMP with a
      cell-penetrating peptide enhances both cellular delivery and biological activity
      of the cyclic-di-GMP in murine splenocytes. Furthermore, our findings establish
      that activation of the TLR-dependent and TLR-independent DNA recognition pathways
      through combined use of CpG oligonucleotide (ODN) and CDN results in synergistic
      activity, augmenting cytokine production (IFN-alpha/beta, IL-6, TNF-alpha, IP
      10), costimulatory molecule upregulation (MHC class II, CD86), and antigen
      specific humoral and cellular immunity. Results presented herein indicate that
      3'3'-cGAMP, a recently identified bacterial CDN, is a superior stimulator of IFN
      genes ligand than cyclic-di-GMP in human PBMCs. Collectively, these findings
      suggest that the immune-stimulatory properties of CDNs can be augmented through
      peptide complexation or synergistic use with CpG oligonucleotide and may be of
      interest for the development of CDN-based immunotherapeutic agents. 

PMID- 25581347
TI  - Parents' experiences of managing their child's diabetes using an insulin pump: a
      qualitative study.
AB  - AIMS: Continuous subcutaneous insulin infusion delivered via a pump is
      increasingly recommended for younger children with Type 1 diabetes. Our aims
      were: to understand the impact on parents who care for young children using
      insulin pumps; to help interpret psychological outcomes reported in quantitative
      research; and to inform provision of support to future parents. METHODS: We
      conducted in-depth interviews with 19 parents of children (aged <= 12 years) with
      Type 1 diabetes who used an insulin pump. Data were analysed thematically.
      RESULTS: Parents reported multiple benefits from using insulin pumps, including:
      no longer having to administer painful injections; fewer restrictions on the
      frequency, timing and carbohydrate contents of snacks and meals; and improvements
      in family life and their child's glycaemic control. Parents liked and felt less
      anxious about using bolus calculators to determine insulin doses; however,
      parents also described undertaking additional and unanticipated work to manage
      their child's diabetes using a pump. This included performing more blood glucose
      tests to calculate insulin doses for snacks and to address their concerns that
      the pump increased their child's risk of hypoglycaemia. Some parents reported
      doing additional blood glucose checks because they could adjust pump settings to
      better manage hypo- and hyperglycaemia. CONCLUSIONS: Parents liked and perceived
      benefits for their child and themselves from using an insulin pump; however,
      parents would benefit from being made aware of the additional work involved in
      using a pump and also from education and support to address concerns about
      hypoglycaemia. Better measures to evaluate parents' experiences are also
      recommended.

PMID- 25581349
TI  - Processing of cell-surface signalling anti-sigma factors prior to signal
      recognition is a conserved autoproteolytic mechanism that produces two functional
      domains.
AB  - Cell-surface signalling (CSS) enables Gram-negative bacteria to transduce an
      environmental signal into a cytosolic response. This regulatory cascade involves
      an outer membrane receptor that transmits the signal to an anti-sigma factor in
      the cytoplasmic membrane, allowing the activation of an extracytoplasmic function
      (ECF) sigma factor. Recent studies have demonstrated that RseP-mediated
      proteolysis of the anti-sigma factors is key to sigma(ECF) activation. Using the
      Pseudomonas aeruginosa FoxR anti-sigma factor, we show here that RseP is
      responsible for the generation of an N-terminal tail that likely contains pro
      sigma activity. Furthermore, it has been reported previously that this anti-sigma
      factor is processed in two separate domains prior to signal recognition. Here, we
      demonstrate that this process is common in these types of proteins and that the
      processing event is probably due to autoproteolytic activity. The resulting
      domains interact and function together to transduce the CSS signal. However, our
      results also indicate that this processing event is not essential for activity.
      In fact, we have identified functional CSS anti-sigma factors that are not
      cleaved prior to signal perception. Together, our results indicate that CSS
      regulation can occur through both complete and initially processed anti-sigma
      factors.

PMID- 25581350
TI  - Impact of amphiphilic biomass-dissolving ionic liquids on biological cells and
      liposomes.
AB  - The toxicity of some promising biomass-dissolving amidinium-, imidazolium-, and
      phosphonium-based ionic liquids (ILs), toward two different cell lines, human
      corneal epithelial cells and Escherichia coli bacterial cells, was investigated.
      In addition, dynamic light scattering (DLS) and zeta potential measurements were
      used to study the effect of the ILs on the size and surface charge of some model
      liposomes. Capillary electrophoresis (CE) was used for determination of the
      electrophoretic mobilities of the liposomes and for determination of the critical
      micelle concentration (cmc) of the ILs. The toxicity of the phosphonium ILs was
      highly dependent on the longest linear chain of the IL, due to increasing
      hydrophobicity, with the long-chain phosphonium ILs being toxic while the shorter
      chain versions were significantly less toxic or not toxic at all. Amidinium and
      imidazolium ILs showed no significant effect on the cells, within the
      concentration range used. Moreover, the more hydrophobic ILs were found to have a
      major effect on the surface charges and size distributions of the model
      liposomes, which can lead to disruption of the lipid bilayer. This indicates that
      the cytotoxicity is at least to some extent dependent on direct interactions
      between ILs and the biomembrane. 

PMID- 25581351
TI  - Proposal of Japan Red Cross score for sorafenib therapy in hepatocellular
      carcinoma.
AB  - AIM: There have been no established predictors of the outcome on sorafenib
      therapy for hepatocellular carcinoma (HCC) patients. We aimed to establish a new
      prognostic model suitable for sorafenib in HCC. METHODS: Among 465 HCC patients
      treated with sorafenib in 14 hospitals, we formed a training cohort with 270
      patients at seven hospitals located in West Japan and a validation cohort with
      167 patients at seven hospitals located in East Japan. In the training cohort, we
      examined the relationship between overall survival (OS) and pretreatment clinical
      factors, and structured a new prognostic model. We verified this model in the
      validation cohort and compared with four existing staging models. RESULTS:
      Multivariate analysis demonstrated distant metastases, portal invasion,
      intrahepatic tumor burden of more than 50%, serum alpha-fetoprotein of 150 ng/dL
      or more, des-gamma-carboxyprothrombin of 1200 mAU/mL or more, albumin of 3.5 g/dL
      or less and total bilirubin of more than 1.0 mg/dL were significant independent
      adverse prognostic factors. We calculated a Japan Red Cross (JRC) score with
      these factors and classified three groups: low-, intermediate- or high-risk.
      Their median OS were well stratified (18.0, 8.8 and 3.7 months, respectively, P <
      0.001) in the training cohort. In the validation cohort, OS were also
      statistically stratified (23.9, 10.3 and 2.9 months, P < 0.001). C-statistics of
      the JRC score was 0.755, the highest in the five models, indicating its novel
      predictability. CONCLUSION: Our proposed JRC score well predicts the prognosis of
      sorafenib therapy, and would be useful to plan individualized strategies for
      unresectable HCC.

PMID- 25581352
TI  - Improved oral absorption of doxorubicin by amphiphilic copolymer of lysine-linked
      ditocopherol polyethylene glycol 2000 succinate: in vitro characterization and in
      vivo evaluation.
AB  - In the previous study, we have synthesized an amphiphilic copolymer of
      nanostructure-forming material and P-glycoprotein (P-gp) inhibitor, lysine-linked
      ditocopherol polyethylene glycol 2000 succinate (PLV2K). The cytotoxicty in vitro
      and anticancer efficacy in vivo after intravenous administration of DOX-loaded
      PLV2K micelles (PLV2K-DOX) was found more effective than DOX solution (DOX-Sol).
      However, its performance and mechanism on oral absorption of doxorubicin are not
      well understood yet. PLV2K-DOX are spherical micelles with a narrow size
      distribution of 20.53 +/- 2.44 nm. With an in situ intestinal perfusion model,
      the intestinal absorption potential of PLV2K-DOX was evaluated in comparison with
      DOX-Sol. PLV2K-DOX was specifically absorbed in duodenum and ileum sites of rats
      after oral administration. The intestinal absorption rate (Ka) of PLV2K-DOX is
      3.19-, 1.61-, and 1.80-fold higher than that of DOX-Sol in duodenum, jejunum, and
      ileum, respectively. In Caco-2 uptake studies, PLV2K-DOX micelles significantly
      improve the internalized amount of DOX by P-gp inhibition of free PLV2K copolymer
      and endocytosis of DOX-loaded nanoparticles. Moreover, PLV2K-DOX micelles improve
      the membrane permeability of DOX by multiple transcytosis mechanisms, including
      caveolin-, clathrin-dependent, and caveolin-/clathrin-independent transcytosis in
      Caco-2 transport studies. However, the transepithelia electrical resistance
      (TEER) of Caco-2 cellular monolayer is not changed, suggesting no involvement of
      paracellular transport of PLV2K-DOX. In vivo pharmacokinetics in rats following
      oral administration demonstrated that PLV2K-DOX demonstrates higher AUC (5.6
      fold) and longer t1/2 (1.2-fold) than DOX-Sol. The findings suggest the new PLV2K
      micelles might provide an effective nanoplatform for oral delivery of anticancer
      drugs with poor membrane permeability and low oral bioavailability.

PMID- 25581353
TI  - First you have to row a little boat.

PMID- 25581354
TI  - Editorial comment to Botulinum toxin A injection for the treatment of neurogenic
      detrusor overactivity secondary to spinal cord injury: multi-institutional
      experience in Japan.

PMID- 25581356
TI  - Innervation of the cricothyroid muscle by the recurrent laryngeal nerve.
AB  - BACKGROUND: The recurrent laryngeal nerve (RLN) and the external branch of the
      superior laryngeal nerve (SLN) are generally thought to innervate the
      endolaryngeal muscles and the cricothyroid muscle (CTM), respectively. Meticulous
      anatomic studies found communication between these nerves (ie, the human
      communicating nerve). In this study, we report the innervation of the CTM by the
      RLN. METHODS: We performed electromyographic studies of 50 patients during
      thyroidectomy (20 total and 30 hemithyroidectomies). During surgery, the external
      branch of the SLN, RLN, and vagus nerve were stimulated. Responses were evaluated
      by visual observation of the CTM and by electromyographies through needle
      electrodes inserted into the CTM. RESULTS: Seventy CTMs were evaluated. The RLN
      stimulation yielded both visible contractions and clear electromyographic
      responses (>300 uV) in 27 (39%), either response in 24 (34%), and neither
      response in 19 (27%) of the CTMs. The vagus stimulation gave similar results.
      CONCLUSION: The RLN innervated the CTM at least in 39% cases. (c) 2015 Wiley
      Periodicals, Inc. Head Neck 38: E441-E445, 2016.

PMID- 25581355
TI  - Wnt5a is involved in the pathogenesis of cutaneous lichen planus.
AB  - BACKGROUND: Cutaneous lichen planus (CLP) is a chronic inflammatory and immune
      mediated disease. Wnt5a is one of the most extensively studied Wnt proteins, and
      has important functions in stimulating inflammation, cell proliferation, cell
      fate determination and cell differentiation. Wnt5a expression in CLP has not been
      comprehensively studied to date. AIM: To determine the expression and
      distribution of Wnt5a in CLP. METHODS: Skin samples were obtained from patients
      with CLP and healthy controls (HCs). The WNT5A gene was detected by real-time
      quantitative PCR, and Wnt5a protein by immunohistochemical analysis and western
      blotting. RESULTS: WNT5A mRNA was upregulated in CLP samples compared with the HC
      skin samples (P < 0.001). Wnt5a protein was overexpressed in all layers of the
      epidermis and dermis in CLP lesions compared with HC skin (all P < 0.001). These
      results were confirmed by western blotting. CONCLUSIONS: The data presented in
      this study suggest that Wnt5a pathway may play an important role in the
      pathogenesis of CLP.

PMID- 25581357
TI  - Immunophenotypic characteristics of breast implant-associated anaplastic large
      cell lymphoma by flow cytometry.

PMID- 25581358
TI  - Root cause analysis of critical events in neurosurgery, New South Wales.
AB  - BACKGROUND: Adverse events reportedly occur in 5% to 10% of health care episodes.
      Not all adverse events are the result of error; they may arise from systemic
      faults in the delivery of health care. Catastrophic events are not only
      physically devastating to patients, but they also attract medical liability and
      increase health care costs. Root cause analysis (RCA) has become a key tool for
      health care services to understand those adverse events. METHOD: This study is a
      review of all the RCA case reports involving neurosurgical patients in New South
      Wales between 2008 and 2013. The case reports and data were obtained from the
      Clinical Excellence Commission database. The data was then categorized by the
      root causes identified and the recommendations suggested by the RCA committees.
      RESULTS: Thirty-two case reports were identified in the RCA database. Breaches in
      policy account for the majority of root causes identified, for example, delays in
      transfer of patients or wrong-site surgery, which always involved poor adherence
      to correct patient and site identification procedures. The RCA committees'
      recommendations included education for staff, and improvements in rostering and
      procedural guidelines. CONCLUSION: RCAs have improved the patient safety profile;
      however, the RCA committees have no power to enforce any recommendation or ensure
      compliance. A single RCA may provide little learning beyond the unit and staff
      involved. However, through aggregation of RCA data and dissemination strategies,
      health care workers can learn from adverse events and prevent future events from
      occurring.

PMID- 25581359
TI  - Complementary adaptive processes contribute to the developmental plasticity of
      spatial hearing.
AB  - Spatial hearing evolved independently in mammals and birds and is thought to
      adapt to altered developmental input in different ways. We found, however, that
      ferrets possess multiple forms of plasticity that are expressed according to
      which spatial cues are available, suggesting that the basis for adaptation may be
      similar across species. Our results also provide insight into the way sound
      source location is represented by populations of cortical neurons. 

PMID- 25581360
TI  - Contribution of mGluR5 to pathophysiology in a mouse model of human chromosome
      16p11.2 microdeletion.
AB  - Human chromosome 16p11.2 microdeletion is the most common gene copy number
      variation in autism, but the synaptic pathophysiology caused by this mutation is
      largely unknown. Using a mouse with the same genetic deficiency, we found that
      metabotropic glutamate receptor 5 (mGluR5)-dependent synaptic plasticity and
      protein synthesis was altered in the hippocampus and that hippocampus-dependent
      memory was impaired. Notably, chronic treatment with a negative allosteric
      modulator of mGluR5 reversed the cognitive deficit. 

PMID- 25581361
TI  - Surface diffusion of astrocytic glutamate transporters shapes synaptic
      transmission.
AB  - Control of the glutamate time course in the synapse is crucial for excitatory
      transmission. This process is mainly ensured by astrocytic transporters, high
      expression of which is essential to compensate for their slow transport cycle.
      Although molecular mechanisms regulating transporter intracellular trafficking
      have been identified, the relationship between surface transporter dynamics and
      synaptic function remains unexplored. We found that GLT-1 transporters were
      highly mobile on rat astrocytes. Surface diffusion of GLT-1 was sensitive to
      neuronal and glial activities and was strongly reduced in the vicinity of
      glutamatergic synapses, favoring transporter retention. Notably, glutamate
      uncaging at synaptic sites increased GLT-1 diffusion, displacing transporters
      away from this compartment. Functionally, impairing GLT-1 membrane diffusion
      through cross-linking in vitro and in vivo slowed the kinetics of excitatory
      postsynaptic currents, indicative of a prolonged time course of synaptic
      glutamate. These data provide, to the best of our knowledge, the first evidence
      for a physiological role of GLT-1 surface diffusion in shaping synaptic
      transmission. 

PMID- 25581362
TI  - Olfactory bulb coding of odors, mixtures and sniffs is a linear sum of odor time
      profiles.
AB  - The olfactory system receives intermittent and fluctuating inputs arising from
      dispersion of odor plumes and active sampling by the animal. Previous work has
      suggested that the olfactory transduction machinery and excitatory-inhibitory
      olfactory bulb circuitry generate nonlinear population trajectories of neuronal
      activity that differ across odorants. Here we show that individual mitral/tufted
      (M/T) cells sum inputs linearly across odors and time. By decoupling odor
      sampling from respiration in anesthetized rats, we show that M/T cell responses
      to arbitrary odor waveforms and mixtures are well described by odor-specific
      impulse responses convolved with the odorant's temporal profile. The same impulse
      responses convolved with the respiratory airflow predict the classical
      respiration-locked firing of olfactory bulb neurons and several other reported
      response properties of M/T cells. These results show that the olfactory bulb
      linearly processes fluctuating odor inputs, thereby simplifying downstream
      decoding of stimulus identity and temporal dynamics. 

PMID- 25581365
TI  - Copper as a robust and transparent electrocatalyst for water oxidation.
AB  - Copper metal is in theory a viable oxidative electrocatalyst based on surface
      oxidation to Cu(III) and/or Cu(IV) , but its use in water oxidation has been
      impeded by anodic corrosion. The in situ formation of an efficient interfacial
      oxygen-evolving Cu catalyst from Cu(II) in concentrated carbonate solutions is
      presented. The catalyst necessitates use of dissolved Cu(II) and accesses the
      higher oxidation states prior to decompostion to form an active surface film,
      which is limited by solution conditions. This observation and restriction led to
      the exploration of ways to use surface-protected Cu metal as a robust
      electrocatalyst for water oxidation. Formation of a compact film of CuO on Cu
      surface prevents anodic corrosion and results in sustained catalytic water
      oxidation. The Cu/CuO surface stabilization was also applied to Cu nanowire
      films, which are transparent and flexible electrocatalysts for water oxidation
      and are an attractive alternative to ITO-supported catalysts for
      photoelectrochemical applications. 

PMID- 25581364
TI  - Dynamic routing of task-relevant signals for decision making in dorsolateral
      prefrontal cortex.
AB  - Neurons in the dorsolateral prefrontal cortex (DLPFC) encode a diverse array of
      sensory and mnemonic signals, but little is known about how this information is
      dynamically routed during decision making. We analyzed the neuronal activity in
      the DLPFC of monkeys performing a probabilistic reversal task where information
      about the probability and magnitude of reward was provided by the target color
      and numerical cues, respectively. The location of the target of a given color was
      randomized across trials and therefore was not relevant for subsequent choices.
      DLPFC neurons encoded signals related to both task-relevant and irrelevant
      features, but only task-relevant mnemonic signals were encoded congruently with
      choice signals. Furthermore, only the task-relevant signals related to previous
      events were more robustly encoded following rewarded outcomes. Thus, multiple
      types of neural signals are flexibly routed in the DLPFC so as to favor actions
      that maximize reward. 

PMID- 25581366
TI  - Multi-body coalescence in Pickering emulsions.
AB  - Particle-stabilized Pickering emulsions have shown unusual behaviours such as the
      formation of non-spherical droplets and the sudden halt of coalescence between
      individual droplets. Here we report another unusual behaviour of Pickering
      emulsions-the simultaneous coalescence of multiple droplets in a single event.
      Using latex particles, silica particles and carbon nanotubes as model
      stabilizers, we show that multi-body coalescence can occur in both water-in-oil
      and oil-in-water emulsions. The number of droplets involved in the nth coalscence
      event equals four times the corresponding number of the tetrahedral sequence in
      close packing. Furthermore, coalescence is promoted by repulsive latex and silica
      particles but inhibited by attractive carbon nanotubes. The revelation of multi
      body coalescence is expected to help better understand Pickering emulsions in
      natural systems and improve their designs in engineering applications. 

PMID- 25581367
TI  - Description of relational processes: recent changes in DSM-5 and proposals for
      ICD-11.
AB  - Epidemiologic, prospective, and retrospective research confirms that family
      relational variables are significant risk factors for the development of mental
      and physical health problems in children as well as adults. In addition,
      relationships also play a moderating role in the maintenance, exacerbation, or
      amelioration of chronic health problems. Although acknowledgment of the
      importance of these variables in the pathophysiology of a number of health
      conditions is reaching more prominence, the integration of assessments of family
      factors as part of standard health care has made little progress. With the
      arrival of the Affordable Care Act in the United States, there is a desire for
      earlier identification of these risk factors, and the ability to implement
      prevention programs that reduce risk, and enhance protective factors. On a global
      level, there is increased awareness of the health impact of relational problems,
      for example, many countries have attempted to implement programs to decrease
      domestic violence. More reliable and standardized assessments of key relational
      processes will enhance both of these missions, and allow comparison of a variety
      of prevention and intervention programs. This article discusses progress over the
      last decade in constructing more reliable definitions of relationship processes,
      how these have been integrated into the Diagnostic and Statistical Manual 5th
      edition (DSM-5), and progress toward implementation into the World Health
      Organization's International Classification of Diseases (ICD-11). 

PMID- 25581363
TI  - Neddylation inhibition impairs spine development, destabilizes synapses and
      deteriorates cognition.
AB  - Neddylation is a ubiquitylation-like pathway that controls cell cycle and
      proliferation by covalently conjugating Nedd8 to specific targets. However, its
      role in neurons, nonreplicating postmitotic cells, remains unexplored. Here we
      report that Nedd8 conjugation increased during postnatal brain development and is
      active in mature synapses, where many proteins are neddylated. We show that
      neddylation controls spine development during neuronal maturation and spine
      stability in mature neurons. We found that neddylated PSD-95 was present in
      spines and that neddylation on Lys202 of PSD-95 is required for the proactive
      role of the scaffolding protein in spine maturation and synaptic transmission.
      Finally, we developed Nae1(CamKIIalpha-CreERT2) mice, in which neddylation is
      conditionally ablated in adult excitatory forebrain neurons. These mice showed
      synaptic loss, impaired neurotransmission and severe cognitive deficits. In
      summary, our results establish neddylation as an active post-translational
      modification in the synapse regulating the maturation, stability and function of
      dendritic spines. 

PMID- 25581369
TI  - American Heart Association 2014 Scientific Sessions.

PMID- 25581368
TI  - Retrieval of Tip-embedded Inferior Vena Cava Filters by Using the Endobronchial
      Forceps Technique: Experience at a Single Institution.
AB  - PURPOSE: To evaluate the use of endobronchial forceps to retrieve tip-embedded
      inferior vena cava (IVC) filters. MATERIALS AND METHODS: This institutional
      review board-approved, HIPAA-compliant retrospective study included 114 patients
      who presented with tip-embedded IVC filters for removal from January 2005 to
      April 2014. The included patients consisted of 77 women and 37 men with a mean
      age of 43 years (range, 18-79 years). Filters were identified as tip embedded by
      using rotational venography. Rigid bronchoscopy forceps were used to dissect the
      tip or hook of the filter from the wall of the IVC. The filter was then removed
      through the sheath by using the endobronchial forceps. Statistical analysis
      entailed calculating percentages, ranges, and means. RESULTS: The endobronchial
      forceps technique was used to successfully retrieve 109 of 114 (96%) tip-embedded
      IVC filters on an intention-to-treat basis. Five failures occurred in four
      patients in whom the technique was attempted but failed and one patient in whom
      retrieval was not attempted. Filters were in place for a mean of 465 days (range,
      31-2976 days). The filters in this study included 10 Recovery, 33 G2, eight G2X,
      11 Eclipse, one OptEase, six Option, 13 Gunther Tulip, one ALN, and 31 Celect
      filters. Three minor complications and one major complication occurred, with no
      permanent sequelae. CONCLUSION: The endobronchial forceps technique can be safely
      used to remove tip-embedded IVC filters.

PMID- 25581370
TI  - Sufu and Kif7 in limb patterning and development.
AB  - BACKGROUND: The vertebrate digit pattern is defined by the morphogen Sonic
      hedgehog (Shh), which controls the activity of Gli transcription factors. Gli1, 2
      and 3 are dynamically expressed during patterning. Downstream of Shh, their
      activity is regulated by Sufu and Kif7, core components of the Shh signaling
      cascade. The precise roles of these regulators during limb development have not
      been fully described. We analyze the role of Sufu and Kif7 in the limb and
      demonstrate that their loss has distinct and synergistic effects on Gli activity
      and digit pattern. RESULTS: Using a series of mouse mutants, we show that Sufu
      and Kif7 are expressed throughout limb development and their deletion has
      distinct effects on Gli levels and limb formation. Concomitant deletion of Sufu
      and Kif7 results in constitutive pathway activity and severe limb truncation.
      This is consistent with the recently published two-population model, which
      suggests that precocious activation of Shh signaling inhibits organizing center
      formation and limb outgrowth. CONCLUSIONS: Together, our findings demonstrate
      that perturbations of Sufu and Kif7 affect Gli activity and recapitulate the full
      spectrum of vertebrate limb defects, ranging from severe truncation to
      polydactyly.

PMID- 25581371
TI  - Ionic liquid-assisted synthesis of multicolor luminescent silica nanodots and
      their use as anticounterfeiting ink.
AB  - Here we propose a simple route for the fabrication of silica nanodots which are
      strongly photoluminescent in both solution and the solid state based on the use
      of ionic liquids (ILs). It is found that the ILs not only provides the
      environment for the reaction but also contributes to the quantum yield (QY) of
      the silica nanodots. In particular, the produced silica nanodots also displayed
      excitation-dependent photoluminescence and temperature sensitive properties.
      Based on the unique optical properties, the as-prepared nanomaterial was used for
      anticounterfeiting application and the results demonstrated the great potential
      of the silica nanodots alone or combined with other fluorescent material of
      unicolor for an improved anticounterfeiting technology. This simple approach and
      the resulting outstanding combination of properties make the prepared silica
      nanodots highly promising for myriad applications in areas such as fluorescent
      anticounterfeiting, optoelectronic devices, medical diagnosis and biological
      imaging. 

PMID- 25581372
TI  - Treatment intensity and childhood apraxia of speech.
AB  - BACKGROUND: Intensive treatment has been repeatedly recommended for the treatment
      of speech deficits in childhood apraxia of speech (CAS). However, differences in
      treatment outcomes as a function of treatment intensity have not been
      systematically studied in this population. AIM: To investigate the effects of
      treatment intensity on outcome measures related to articulation, functional
      communication and speech intelligibility for children with CAS undergoing
      individual motor speech intervention. METHODS & PROCEDURES: A total of 37
      children (32-54 months of age) with CAS received 1*/week (lower intensity) or
      2*/week (higher intensity) individual motor speech treatment for 10 weeks.
      Assessments were carried out before and after a 10-week treatment block to study
      the effects of variations in treatment intensity on the outcome measures.
      OUTCOMES & RESULTS: The results indicated that only higher intensity treatment
      (2*/week) led to significantly better outcomes for articulation and functional
      communication compared with 1*/week (lower intensity) intervention. Further,
      neither lower nor higher intensity treatment yielded a significant change for
      speech intelligibility at the word or sentence level. In general, effect sizes
      for the higher intensity treatment groups were larger for most variables compared
      with the lower intensity treatment group. CONCLUSIONS & IMPLICATIONS: Overall,
      the results of the current study may allow for modification of service delivery
      and facilitate the development of an evidence-based care pathway for children
      with CAS.

PMID- 25581374
TI  - Global transcriptome analysis of peripheral blood identifies the most
      significantly down-regulated genes associated with metabolism regulation in
      Klinefelter syndrome.
AB  - The molecular pathogenesis of Klinefelter Syndrome (KS) is not fully understood.
      The aim of this study was to determine differences in gene expression patterns
      between KS patients and control individuals to help identify disease-related
      genes and biological pathways. Gene expression profiles of five KS patients and
      five healthy men were determined by microarray; 21 differentially expressed genes
      with a fold-change >1.5 and q-value <0.05 were identified between the groups.
      Genes associated with metabolism regulation and encoding liver fatty acid-binding
      protein (FABP1), aldehyde dehydrogenase 1 family member L1 (ALDH1L1), and
      vitronectin (VTN) were the most-significantly down-regulated in KS, as confirmed
      by quantitative reverse transcription PCR. Notably, none of these differentially
      expressed genes are normally found on the X chromosome. Thus, our results
      indicate that aberrant metabolism is involved in the pathogenesis of KS. Further
      elucidation of the how aberrant expression of metabolism-related genes affect the
      pathogenesis of KS may lead to the development of novel preventative and
      therapeutic strategies.

PMID- 25581375
TI  - "Renewed" "older" motherhood/mothering: a qualitative exploration.
AB  - This UK-based qualitative study explored multiparous women's experiences of being
      "older" mothers. Respondents were "renewed mothers" who had a child/children
      relatively early in their reproductive careers and then again after 35 years of
      age. Key themes arising from the empirical data were: instrumental role of male
      partners in post-35 mothering, purported "renewal" of self in the face of
      menopause/diminution of mothering, caring for teenagers and babies/toddlers
      simultaneously, and subjection to criticisms of "wrong-aged" motherhood.
      Experiences of "renewed" "older" mothers suggest significant hard work is
      necessitated both in terms of mothering and presentation of self as an
      appropriate mother. 

PMID- 25581373
TI  - Ammonia-oxidizing Bacteria of the Nitrosospira cluster 1 dominate over ammonia
      oxidizing Archaea in oligotrophic surface sediments near the South Atlantic Gyre.
AB  - Sediments across the Namibian continental margin feature a strong microbial
      activity gradient at their surface. This is reflected in ammonium concentrations
      of < 10 MUM in oligotrophic abyssal plain sediments near the South Atlantic Gyre
      compared with ammonium concentrations of > 700 MUM in upwelling areas near the
      coast. Here we address changes in apparent abundance and structure of ammonia
      oxidizing archaeal and bacterial communities (AOA and AOB) along a transect of
      seven sediment stations across the Namibian shelf by analysing their respective
      ammonia monooxygenase genes (amoA). The relative abundance of archaeal and
      bacterial amoA (g(-1) DNA) decreased with increasing ammonium concentrations, and
      bacterial amoA frequently outnumbered archaeal amoA at the sediment-water
      interface [0-1 cm below seafloor (cmbsf)]. In contrast, AOA were apparently as
      abundant as AOB or dominated in several deeper (> 10 cmbsf), anoxic sediment
      layers. Phylogenetic analyses showed a change within the AOA community along the
      transect, from two clusters without cultured representatives at the gyre to
      Nitrososphaera and Nitrosopumilus clusters in the upwelling region. AOB almost
      exclusively belonged to the Nitrosospira cluster 1. Our results suggest that this
      predominantly marine AOB lineage without cultured representatives can thrive at
      low ammonium concentrations and is active in the marine nitrogen cycle. 

PMID- 25581377
TI  - Trophic compensation reinforces resistance: herbivory absorbs the increasing
      effects of multiple disturbances.
AB  - Disturbance often results in small changes in community structure, but the
      probability of transitioning to contrasting states increases when multiple
      disturbances combine. Nevertheless, we have limited insights into the mechanisms
      that stabilise communities, particularly how perturbations can be absorbed
      without restructuring (i.e. resistance). Here, we expand the concept of
      compensatory dynamics to include countervailing mechanisms that absorb
      disturbances through trophic interactions. By definition, 'compensation' occurs
      if a specific disturbance stimulates a proportional countervailing response that
      eliminates its otherwise unchecked effect. We show that the compounding effects
      of disturbances from local to global scales (i.e. local canopy-loss,
      eutrophication, ocean acidification) increasingly promote the expansion of weedy
      species, but that this response is countered by a proportional increase in
      grazing. Finally, we explore the relatively unrecognised role of compensatory
      effects, which are likely to maintain the resistance of communities to
      disturbance more deeply than current thinking allows. 

PMID- 25581376
TI  - Inhibitors of CLK protein kinases suppress cell growth and induce apoptosis by
      modulating pre-mRNA splicing.
AB  - Accumulating evidence has demonstrated the importance of alternative splicing in
      various physiological processes, including the development of different diseases.
      CDC-like kinases (CLKs) and serine-arginine protein kinases (SRPKs) are
      components of the splicing machinery that are crucial for exon selection. The
      discovery of small molecule inhibitors against these kinases is of significant
      value, not only to delineate the molecular mechanisms of splicing, but also to
      identify potential therapeutic opportunities. Here we describe a series of small
      molecules that inhibit CLKs and SRPKs and thereby modulate pre-mRNA splicing.
      Treatment with these small molecules (Cpd-1, Cpd-2, or Cpd-3) significantly
      reduced the levels of endogenous phosphorylated SR proteins and caused
      enlargement of nuclear speckles in MDA-MB-468 cells. Additionally, the compounds
      resulted in splicing alterations of RPS6KB1 (S6K), and subsequent depletion of
      S6K protein. Interestingly, the activity of compounds selective for CLKs was well
      correlated with the activity for modulating S6K splicing as well as growth
      inhibition of cancer cells. A comprehensive mRNA sequencing approach revealed
      that the inhibitors induced splicing alterations and protein depletion for
      multiple genes, including those involved in growth and survival pathways such as
      S6K, EGFR, EIF3D, and PARP. Fluorescence pulse-chase labeling analyses
      demonstrated that isoforms with premature termination codons generated after
      treatment with the CLK inhibitors were degraded much faster than canonical mRNAs.
      Taken together, these results suggest that CLK inhibitors exhibit growth
      suppression and apoptosis induction through splicing alterations in genes
      involved in growth and survival. These small molecule inhibitors may be valuable
      tools for elucidating the molecular machinery of splicing and for the potential
      development of a novel class of antitumor agents. 

PMID- 25581378
TI  - Evaluation of the pediatric post anesthesia discharge scoring system in an
      ambulatory surgery unit.
AB  - INTRODUCTION: To optimize the care pathway for children scheduled for ambulatory
      surgery, a pediatric postanesthetic discharge scoring system (Ped-PADSS) was
      developed from a score used in adults. The objective of this study was to
      evaluate this score prospectively on a cohort of children who had a day case
      surgical procedure. MATERIALS AND METHODS: This was a single center prospective
      observational study. Inclusion criteria were predefined as follows: children aged
      6 months-16 years at the time of the study, with a scheduled day surgery.
      Discharge was validated by Ped-PADSS scores >=9, obtained at one hour intervals,
      after the return from the operating room and with the agreement of the surgeon.
      The duration of postoperative hospitalization was compared with data collected
      before the implementation of the score using the Student's t-test. RESULTS: From
      February to July 2012, 1060 children were included. One hour after the return
      from the operating room, 97.2% of children were dischargeable using Ped-PADSS.
      Two hours after the return from the operating room, 99.8% of children were
      dischargeable. The median postoperative hospital stay (n = 1041) was reduced by
      69 min compared to the median stay before using the output score (n = 150) (P <
      0.01). CONCLUSION: The Ped-PADSS score allows for the majority of children to be
      discharged 1 h after their return from the postanesthesia care unit. Children who
      were discharged using the Ped-PADSS score returned home in safe and optimal
      conditions.

PMID- 25581379
TI  - Cardiac transplantation from infected donors: is it safe?
AB  - BACKGROUND: Transplantation of a cardiac allograft from an infected donor risks
      transmission of disease to the immunocompromised recipient. Such organs are often
      not utilized despite little supporting evidence. We sought to evaluate outcomes
      following cardiac transplant with the use of an infected allograft. METHODS: The
      UNOS/OPTN database was used to identify first time, adult heart transplant
      recipients from 1995 to 2009. Patients receiving allografts from blood culture
      positive donor (CPD) were compared to those who did not (NCPD). RESULTS: A total
      of 26,813 recipients were included. Nine hundred ninety-five (3.7%) received a
      heart from a CPD. Recipients of hearts from CPDs were more likely to be diabetic
      (24% vs. 20%, p = 0.01), hypertensive (42% vs. 38%, p = 0.02), status 1 (80% vs.
      76%, p = 0.0021), have a BMI > 30 (19% vs. 16%, p = 0.001), on intra-aortic
      balloon pump (IABP) support (7% vs. 5%, p = 0.017), and worse functional status.
      Recipients with a CPD were more likely to be treated for a post-transplant
      infection (28% vs. 23%, p = 0.003) but not for an episode of rejection in the
      first year after transplantation (39% vs. 40%, p = 0.73). Receipt of a CPD
      allograft was not a multivariate predictor for mortality. CPD and NCPD survival
      was similar at one year (86% vs. 87%, p = 0.2585) and 15 years (34% vs. 36%, p =
      0.0929). CONCLUSION: Use of allografts from CPD has no influence on survival
      despite the fact that these recipients tend to have a higher acuity and more
      comorbidities at the time of transplantation. Utilization of a heart from a donor
      with a confirmed blood stream infection should be carefully considered.

PMID- 25581380
TI  - Preoperative findings and visual outcome associated with retinal reattachment
      surgery in dogs: 217 cases (275 eyes).
AB  - OBJECTIVE: Report the correlation of pre-operative findings with visual outcome
      in dogs undergoing retinal reattachment surgery for giant retinal tears.
      PROCEDURES: Retrospective analysis of dogs that underwent pars plana vitrectomy
      (PPV) with silicone oil (SiO) tamponade and endolaser retinopexy at one
      institution. Recorded parameters included signalment, etiology, and duration of
      retinal detachment, observable retinal tissue architecture, visual reflexes, lens
      status, presurgical aqueous flare, visual status postoperatively, and
      complications. RESULTS: Two hundred and seventeen patients (275 eyes) were
      included. Common etiologies of detachment were primary vitreoretinal disease
      (50.5%), lens surgery (35.3%), and hypermature cataracts (6.2%). Immediate
      postoperative anatomic success was noted in 98% of operated eyes. Maintenance or
      return of vision was noted in 74.2% of patients (72% of eyes) through the last
      known follow-up, with return of vision on average 18.5 days postoperatively. In
      those eyes that regained vision, 71.7% had retained vision at the last known
      recheck examination, with an average follow-up time of 550 days. Pre-operative
      findings correlated with postoperative vision included presence of a dazzle
      reflex, presence of a menace response, and retinal tissue architecture. The most
      common complications included migration of SiO into the anterior chamber (49.4%),
      corneal ulceration (25.7%), glaucoma (25.7%), and cataract formation (24.5%).
      CONCLUSION: Giant retinal tears in dogs can be successfully managed via PPV with
      SiO tamponade and endolaser retinopexy. Vision was maintained in the majority of
      cases with long-term follow-up. Patient history and thorough ophthalmic
      examination with attention to retinal tissue architecture are important in
      assessing surgical candidacy.

PMID- 25581381
TI  - Which life course model better explains the association between socioeconomic
      position and periodontal health?
AB  - AIM: To assess whether the relationship between socioeconomic position (SEP) and
      periodontal health fitted the Critical Period or the Social Mobility life course
      models. METHODS: A nationally representative sample of 5570 Korean adults from
      KNHANES IV study. Log-binomial regression models adjusting for adulthood or
      childhood socioeconomic (SES) variables was used to assess independent effects of
      socioeconomic differences for childhood, adulthood and period of transition from
      child to adult in periodontal health. RESULTS: In the Critical Period model,
      poorer periodontal status was associated with SES disadvantage in adulthood and
      not predicted by SES disadvantage in childhood. For the intergenerational Social
      Mobility model, prevalence of current periodontal disease was only different for
      females aged 30-39 and 40-49 years, after adjustment. Prevalence of periodontal
      disease in females was highest in the downwardly mobile group. CONCLUSIONS: The
      Critical Period model was better at explaining association between socioeconomic
      position and periodontal health, such as the adulthood socioeconomic variables
      (SEP), had a stronger effect than childhood factors on periodontal disease. The
      Social Mobility model explained more of the variation in the association between
      SEP and periodontal health among women than among men.

PMID- 25581382
TI  - The tell-tale look: viewing time, preferences, and prices.
AB  - Even the simplest choices can prompt decision-makers to balance their preferences
      against other, more pragmatic considerations like price. Thus, discerning
      people's preferences from their decisions creates theoretical, empirical, and
      practical challenges. The current paper addresses these challenges by
      highlighting some specific circumstances in which the amount of time that people
      spend examining potential purchase items (i.e., viewing time) can in fact reveal
      their preferences. Our model builds from the gazing literature, in a purchasing
      context, to propose that the informational value of viewing time depends on
      prices. Consistent with the model's predictions, four studies show that when
      prices are absent or moderate, viewing time provides a signal that is consistent
      with a person's preferences and purchase intentions. When prices are extreme or
      consistent with a person's preferences, however, viewing time is a less reliable
      predictor of either. Thus, our model highlights a price-contingent "viewing
      bias," shedding theoretical, empirical, and practical light on the psychology of
      preferences and visual attention, and identifying a readily observable signal of
      preference. 

PMID- 25581385
TI  - Abstracts of the AAGBI WSM, 14-16 January 2015, London, England.

PMID- 25581383
TI  - Safety and Utility of Quantitative Sensory Testing among Adults with Sickle Cell
      Disease: Indicators of Neuropathic Pain?
AB  - OBJECTIVES: Pain is the hallmark symptom of sickle cell disease (SCD), yet the
      types of pain that these patients experience, and the underlying mechanisms, have
      not been well characterized. The study purpose was to determine the safety and
      utility of a mechanical and thermal quantitative sensory testing (QST) protocol
      and the feasibility of utilizing neuropathic pain questionnaires among adults
      with SCD. METHODS: A convenience sample (N = 25, 18 women, mean age 38.5 +/- 12.5
      [20-58 years]) completed self-report pain and quality-of-life tools. Subjects
      also underwent testing with the TSA-II NeuroSensory Analyzer and calibrated von
      Frey microfilaments. RESULTS: We found that the QST protocol was safe and did not
      stimulate a SCD pain crisis. There was evidence of central sensitization (n =
      15), peripheral sensitization (n = 1), a mix of central and peripheral
      sensitization (n = 8), or no sensitization (n = 1). The neuropathic pain self
      report tools were feasible with evidence of construct validity; 40% of the
      subjects reported S-LANSS scores that were indicative of neuropathic pain and had
      evidence of central, peripheral or mixed sensitization. DISCUSSION: The QST
      protocol can be safely conducted in adults with SCD and provides evidence of
      central or peripheral sensitization, which is consistent with a neuropathic
      component to SCD pain. These findings are novel, warrant a larger confirmatory
      study, and indicate the need for normative QST data from African American adults
      and older adults.

PMID- 25581387
TI  - Nicotine produces chronic behavioral sensitization with changes in accumbal
      neurotransmission and increased sensitivity to re-exposure.
AB  - Tobacco use is often associated with long-term addiction as well as high risk of
      relapse following cessation. This is suggestive of persistent neural adaptations,
      but little is known about the long-lasting effects of nicotine on neural
      circuits. In order to investigate the long-term effects of nicotine exposure,
      Wistar rats were treated for 3 weeks with nicotine (0.36 mg/kg), and the duration
      of behavioral and neurophysiological adaptations was evaluated 7 months later. We
      found that increased drug-induced locomotion persisted 7 months after the initial
      behavioral sensitization. In vitro analysis of synaptic activity in the core and
      shell of the nucleus accumbens (nAc) revealed a decrease in input/output function
      in both regions of nicotine-treated rats as compared to vehicle-treated control
      rats. In addition, administration of the dopamine D2 receptor agonist quinpirole
      (5 MUM) significantly increased evoked population spike amplitude in the nAc
      shell of nicotine-treated rats as compared to vehicle-treated control rats. To
      test whether nicotine exposure creates long-lasting malleable circuits, animals
      were re-exposed to nicotine 7 months after the initial exposure. This treatment
      revealed an increased sensitivity to nicotine among animals previously exposed to
      nicotine, with higher nicotine-induced locomotion responses than observed
      initially. In vitro electrophysiological recordings in re-exposed rats detected
      an increased sensitivity to dopamine D2 receptor activation. These results
      suggest that nicotine produces persistent neural adaptations that make the system
      sensitive and receptive to future nicotine re-exposure.

PMID- 25581386
TI  - Heritability of periodontal bone loss in mice.
AB  - BACKGROUND: Periodontitis is an inflammatory disease of the periodontal tissues
      that compromises tooth support and can lead to tooth loss. Although bacterial
      biofilm is central in disease pathogenesis, the host response plays an important
      role in the progression and severity of periodontitis. Indeed, clinical genetic
      studies indicate that periodontitis is 50% heritable. In this study, we
      hypothesized that lipopolysaccharide (LPS) injections lead to a strain-dependent
      periodontal bone loss pattern. MATERIAL AND METHODS: We utilized five inbred
      mouse strains that derive the recombinant strains of the hybrid mouse diversity
      panel. Mice received Porphyromonas gingivalis-LPS injections for 6 wk. RESULTS
      AND CONCLUSION: Micro-computed tomography analysis demonstrated a statistically
      significant strain-dependent bone loss. The most susceptible strain, C57BL/6J,
      had a fivefold higher LPS-induced bone loss compared to the most resistant
      strain, A/J. More importantly, periodontal bone loss revealed 49% heritability,
      which closely mimics periodontitis heritability for patients. To evaluate further
      the functional differences that underlie periodontal bone loss, osteoclast
      numbers of C57BL/6J and A/J mice were measured in vivo and in vitro. In vitro
      analysis of osteoclastogenic potential showed a higher number of osteoclasts in
      C57BL/6J compared to A/J mice. In vivo LPS injections statistically significantly
      increased osteoclast numbers in both groups. Importantly, the number of
      osteoclasts was higher in C57BL/6J vs. A/J mice. These data support a significant
      role of the genetic framework in LPS-induced periodontal bone loss and the
      feasibility of utilizing the hybrid mouse diversity panel to determine the
      genetic factors that affect periodontal bone loss. Expanding these studies will
      contribute in predicting patients genetically predisposed to periodontitis and in
      identifying the biological basis of disease susceptibility.

PMID- 25581388
TI  - Urinary biomarkers after donor nephrectomy.
AB  - As the beginning of living-donor kidney transplantation, physicians have
      expressed concern about the possibility that unilateral nephrectomy can be
      harmful to a healthy individual. To investigate whether the elevated intra
      abdominal pressure (IAP) during laparoscopic donor nephrectomy causes early
      damage to the remaining kidney, we evaluated urine biomarkers after laparoscopic
      donor nephrectomy. We measured albumin and alpha-1-microglobulin (alpha-1-MGB) in
      urine samples collected during and after open and laparoscopic donor nephrectomy
      and laparoscopic cholecystectomy and colectomy. Additionally, kidney injury
      molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were
      measured in urine samples collected during and after laparoscopic donor
      nephrectomy and colectomy. The same biomarkers were studied in patients randomly
      assigned to standard or low IAP during laparoscopic donor nephrectomy. We
      observed a peak in urinary albumin excretion during all procedures. Urine alpha-1
      MGB rose in the postoperative period with a peak on the third postoperative day
      after donor nephrectomy. Urine alpha-1-MGB did not increase after laparoscopic
      cholecystectomy and colectomy. After laparoscopic nephrectomy, we observed slight
      increases in urine KIM-1 during surgery and in urine NGAL at day 2-3 after the
      procedure. After laparoscopic colectomy, both KIM-1 and NGAL were increased in
      the postoperative period. There were no differences between the high- and low
      pressure procedure. Elevated urinary alpha-1-MGB suggests kidney damage after
      donor nephrectomy, occurring irrespective of IAP during the laparoscopic
      procedure. 

PMID- 25581389
TI  - Computed tomographic pulmonary angiography: clinical implications of a limited
      negative result.

PMID- 25581391
TI  - Nanoscale frictional behavior of graphene on SiO2 and Ni(111) substrates.
AB  - Friction characteristics of graphene deposited on different substrates have been
      studied by atomic force microscopy (AFM). In particular, we compared mechanically
      exfoliated graphene transferred over Si/SiO2 with respect to monolayer (ML)
      graphene grown in our laboratory by low temperature chemical vapor deposition on
      Ni(111) single crystal. Friction force measurements by AFM have been carried out
      as function of load under different environment conditions, namely vacuum (10(-5)
      Torr), nitrogen and air. The typical decrease of friction force with increasing
      number of layers has been observed on graphene over Si/SiO2 in all environment
      including vacuum. Continuum mechanical approximation has been used to analyze the
      friction versus load curves of ML graphene on Ni(111). Analysis shows that
      Derjaguin-Mueller-Toporov model is in good agreement with our experimental data
      indicating that overall behavior of the interface graphene-Ni(111) is relatively
      rigid respect to out of plane deformations. This result is consistent with the
      structural characteristics of the interface since graphene grows in registry with
      Ni(111) surface with covalent bonding character. Finally, the shear strength and
      the work of adhesion of the two systems with respect to AFM tip in vacuum have
      been compared. The result of this procedure indicates that shear strength and
      work of adhesion measured on graphene-Si/SiO2 interface are always greater than
      those on graphene-Ni(111) interface.

PMID- 25581390
TI  - Utility of bilirubins and bile acids as endogenous biomarkers for the inhibition
      of hepatic transporters.
AB  - It is useful to identify endogenous substrates for the evaluation of drug-drug
      interactions via transporters. In this study, we investigated the utility of
      bilirubins, substrates of OATPs and MRP2, and bile acids and substrates of NTCP
      and BSEP, as biomarkers for the inhibition of transporters. In rats administered
      20 and 80 mg/kg rifampicin, the plasma levels of bilirubin glucuronides were
      elevated, gradually decreased, and almost returned to the baseline level at 24
      hours after administration without an elevation of alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST). This result indicates the transient
      inhibition of rOatps and/or rMrp2. Although the correlation between free plasma
      concentrations and IC50 values of rOatps depended on the substrates used in the
      in vitro studies, the inhibition of rOatps by rifampicin was confirmed in the in
      vivo study using valsartan as a substrate of rOatps. In rats administered 10 and
      30 mg/kg cyclosporin A, the plasma levels of bile acids were elevated and
      persisted for up to 24 hours after administration without an elevation of ALT and
      AST. This result indicates the continuous inhibition of rNtcp and/or rBsep,
      although there were differences between the free plasma or liver concentrations
      and IC50 values of rNtcp or rBsep, respectively. This study suggests that the
      monitoring of bilirubins and bile acids in plasma is useful in evaluating the
      inhibitory potential of their corresponding transporters. 

PMID- 25581392
TI  - Unraveling the degradation of artificial amide bonds in nylon oligomer hydrolase:
      from induced-fit to acylation processes.
AB  - To elucidate how the nylon oligomer hydrolase (NylB) acquires its peculiar
      degradation activity towards non-biological amide bonds, we inspected the
      underlying enzymatic processes going from the induced-fit upon substrate binding
      to acylation. Specifically we investigated the mutational effects of two mutants,
      Y170F and D181G, indicated in former experiments as crucial systems because of
      their specific amino acid residues. Therefore, by adopting first-principles
      molecular dynamics complemented with metadynamics we provide a detailed insight
      into the underlying acylation mechanism. Our results show that while in the wild
      type (WT) the Tyr170 residue points the NH group towards the proton-acceptor site
      of an artificial amide bond, hence ready to react, in the Y170F this does not
      occur. The reason is ascribed to the absence of Tyr170 in the mutant, which is
      replaced by phenylalanine, which is unable to form hydrogen bond with the amide
      bond; thus, resulting in an increase in the activation barrier of more than 10
      kcal mol(-1). Nonetheless, despite the lack of hydrogen bonding between the Y170F
      and the substrate, the highest free energy barrier for the induced-fit is similar
      to that of WT. This seems to suggest that in the induced-fit process, kinetics is
      little affected by the mutation. On the basis of additional structural homology
      analyses on the enzymes of the same family, we suggest that natural selection is
      responsible for the development of the peculiar hydrolytic activity of
      Arthrobacter sp. KI72. 

PMID- 25581393
TI  - Neuroticism scores increase with late-life cognitive decline.
AB  - OBJECTIVE: Neuroticism has been reported as both a risk factor for cognitive
      decline and a characteristic that increases in parallel with the development of
      mild cognitive impairment (MCI) and dementia. However, the evidence for these
      associations is inconclusive, and whether effects are stronger for particular
      cognitive domains is unknown. We investigated these issues and determined if
      associations differ among different components of neuroticism. METHODS: A
      neuroticism scale (NEO-FFI) and neuropsychological test battery were administered
      to 603 older adults without dementia, with 493 of these reassessed two years
      later. Diagnoses of MCI and dementia (at follow-up) were made, and global
      cognition and performance in six cognitive domains quantified. The neuroticism
      components were negative affect, self-reproach, and proneness to psychological
      distress. RESULTS: For the whole sample, neuroticism scores remained stable
      between baseline (15.3 +/- 7.0) and follow-up (15.5 +/- 7.0), as did all
      neuroticism component scores. However, there were declines in global cognition (p
      < 0.05) and particular cognitive domains (p < 0.001). Higher neuroticism was
      associated with poorer cognition cross-sectionally (p < 0.01), but did not
      predict cognitive decline. For 43 participants who developed incident MCI or
      dementia, there were increases in neuroticism (15.3 +/- 6.4 to 17.1 +/- 8.3, p <
      0.05) and negative affect (p < 0.05). Declines in all cognitive measures except
      executive function were associated with increases in neuroticism and component
      scores (p < 0.05). CONCLUSIONS: Late-life cognitive decline is associated with an
      increase in neuroticism scores. However, associations vary between different
      cognitive domains and components of neuroticism. An increase in neuroticism or
      negative affect scores may be a sign of MCI or dementia.

PMID- 25581394
TI  - Fire risk reduction through a community-based risk assessment: reflections from
      Makola Market, Accra, Ghana.
AB  - This paper explores the level of vulnerability to the hazard of fire that exists
      in Makola Market in Accra, Ghana, and assesses how this threat can be reduced
      through a community-based risk assessment. It examines the perceptions of both
      market-stall occupants and primary stakeholders regarding the hazard of fire, and
      analyses the availability of local assets (coping strategies) with which to
      address the challenge. Through an evaluation of past instances of fire, as well
      as in-depth key stakeholder interviews, field visits, and observations, the study
      produces a detailed hazard map of the market. It goes on to recommend that
      policymakers consider short-to-long-term interventions to reduce the degree of
      risk. By foregrounding the essence of holistic and integrated planning, the paper
      calls for the incorporation of disaster mitigation measures in the overall urban
      planning process and for the strict enforcement of relevant building and fire
      safety codes by responsible public agencies. 

PMID- 25581395
TI  - Structure-assisted functional anchor implantation in robust metal-organic
      frameworks with ultralarge pores.
AB  - A facile functionalization assisted by the structural attributes of PCN-333 has
      been studied while maintaining the integrity of the parent MOF including
      ultralarge pores, chemical robustness, and crystallinity. Herein we thoroughly
      analyzed ligand exchange phenomena in PCN-333 and demonstrate that the extent of
      exchange can be tailored by varying the exchange conditions as potential
      applications may require. Through this method a variety of functional groups are
      incorporated into PCN-333. To further show the capabilities of this system
      introduction of a BODIPY fluorophore as a secondary functionality was performed
      to the functionalized framework via a click reaction. We anticipate the PCN-333
      with functional anchor can serve as a stable platform for further chemistry to be
      explored in future applications. 

PMID- 25581396
TI  - Alkaloidal metabolites from a marine-derived Aspergillus sp. fungus.
AB  - Fumiquinazoline S (1), a new quinazoline-containing alkaloid, and the known
      fumiquinazolines F (6) and L (7) of the same structural class were isolated from
      the solid-substrate culture of an Aspergillus sp. fungus collected from marine
      submerged wood. In addition, isochaetominines A-C (2-4) and 14-epi
      isochaetominine C (5), new alkaloids possessing an unusual amino acid-based
      tetracyclic core framework related to the fumiquinazolines, were isolated from
      the same fungal strain. The structures of these compounds were determined by
      combined spectroscopic methods, and the absolute configurations were assigned by
      NOESY, ROESY, and advanced Marfey's analyses along with biogenetic
      considerations. The new compounds exhibited weak inhibition against Na(+)/K(+)
      ATPase. 

PMID- 25581397
TI  - Influence of water content on the ablation of skin with a 532 nm nanosecond
      Nd:YAG laser.
AB  - This work reports that the ablation volume and rate of porcine skin changed
      significantly with the change of skin water content. Under the same laser
      irradiation conditions (532 nm Nd:YAG laser, pulse width = 11.5 ns, pulse energy
      = 1.54 J, beam radius = 0.54 mm), the ablation volume dropped by a factor of 4 as
      the skin water content decreased from 40 wt. % (native) to 19 wt. % with a change
      in the ablation rate below and above around 25 wt. %. Based on the ablation
      characteristics observed by in situ shadowgraph images and the calculated tissue
      temperatures, it is considered that an explosive rupture by rapid volumetric
      vaporization of water is responsible for the ablation of the high water content
      of skin, whereas thermal disintegration of directly irradiated surface layer is
      responsible for the low water content of skin.

PMID- 25581398
TI  - Application of deep eutectic solvents in the extraction and separation of target
      compounds from various samples.
AB  - Deep eutectic solvents, as a new type of eco-friendly solvent, have attracted
      increasing attention in chemistry for the extraction and separation of target
      compounds from various samples. To summarize the application of deep eutectic
      solvents, this review highlights some of the unique properties of deep eutectic
      solvents and deep-eutectic-solvent-based materials, as well as their applications
      in extraction and separation. In this paper, the available data and references in
      this field are reviewed to summarize the application developments of deep
      eutectic solvents. Based on the development of deep eutectic solvents, the
      exploitation of new deep eutectic solvents and deep-eutectic-solvent-based
      materials are expected to diversify into extraction and separation. 

PMID- 25581399
TI  - Prosthetic valve thrombosis.
AB  - BACKGROUND: We conducted a retrospective, single center study to evaluate the
      clinical characteristics and outcomes of all consecutive patients with prosthetic
      valve thrombosis (PVT) over a 10 year period. METHODS: Data from 85 episodes of
      PVT in 80 patients treated over a 10-year period between 2001 and 2011 were
      analyzed. The diagnosis of PVT was confirmed by echocardiography and/or
      fluoroscopy. PVT was considered obstructive if there was an increased pressure
      gradient on the echo study or reduced or fixed leaflet mobility on fluoroscopy.
      The primary treatment approaches included: redo surgery or thrombolysis for
      obstructive PVT and the intensification of anticoagulation in nonobstructive PVT.
      RESULTS: The mean age was 49.4 +/- 13.1 years (range: 13-79) and 40% were male.
      Thrombosed valves included 53 mitral, 22 aortic, six tricuspid, and both mitral
      and aortic position in nine patients. Subtherapeutic INR (less than 2.5) was
      observed in 58 patients (68.2%). Ten patients died before any definite
      therapeutic strategy in obstructive PVT. In ten patients, episodes were
      considered nonobstructive. Sixteen patients received fibrinolysis (streptokinase)
      that was successful in nine patients (56.2%). Intracranial hemorrhage occurred in
      three (18.7%) patients, and there were four deaths in this group. In the surgical
      group, 49 patients underwent operation as first line therapy and seven patients
      after failed thrombolysis. One brain hemorrhage and three (5.3%) deaths occurred
      during or after surgery. Total complications were significantly less frequent in
      the surgery group compared with those in the thrombolytic group (14.2% vs. 68.7%,
      p-value < 0.001). Higher NYHA functional class and lower systolic blood pressure
      were associated with in-hospital mortality. CONCLUSION: Thrombolysis is less
      effective and has more complications compared to surgery in treatment of
      obstructive PVT. Compromised hemodynamic status during presentation of these
      patients denotes higher in-hospital mortality.

PMID- 25581401
TI  - Dual-emitting MOF?dye composite for ratiometric temperature sensing.
AB  - A strategy to achieve a ratiometric thermometer by encapsulating luminescent
      perylene dye into the pores of a europium metal-organic framework (MOF) is
      developed. The resulting MOF?dye thermometer exhibits highly temperature
      dependent luminescence intensity ratio over the physiological temperature range,
      with a maximum sensitivity of 1.28%  degrees C(-1) at 20  degrees C.

PMID- 25581400
TI  - Rat animal model for preclinical testing of microparticle urethral bulking
      agents.
AB  - OBJECTIVES: To develop an economic, practical and readily available animal model
      for preclinical testing of urethral bulking therapies, as well as to establish
      feasible experimental methods that allow for complete analysis of hard
      microparticle bulking agents. METHODS: Alumina ceramic beads suspended in
      hyaluronic acid were injected into the proximal urethra of 15 female rats under
      an operating microscope. We assessed overall lower urinary tract function,
      bulking material intraurethral integrity and local host tissue response over
      time. Microphotographs were taken during injection and again 6 months
      postoperatively, before urethral harvest. Urinary flow rate and voiding frequency
      were assessed before and after injection. At 6 months, the urethra was removed
      and embedded in resin. Hard tissue sections were cut using a sawing microtome,
      and processed for histological analysis using scanning electron microscopy, light
      microscopy and immunohistochemistry. RESULTS: Microphotographs of the urethra
      showed complete volume retention of the bulking agent at 6 months. There was no
      significant difference between average urinary frequency and mean urinary flow
      rate at 1 and 3 months postinjection as compared with baseline. Scanning electron
      microscopy proved suitable for evaluation of microparticle size and integrity, as
      well as local tissue remodeling. Light microscopy and immunohistochemistry
      allowed for evaluation of an inflammatory host tissue reaction to the bulking
      agent. CONCLUSIONS: The microsurgical injection technique, in vivo physiology and
      novel hard tissue processing for histology, described in the present study, will
      allow for future comprehensive preclinical testing of urethral bulking therapy
      agents containing microparticles made of a hard material.

PMID- 25581402
TI  - Evaluation of one-dimensional and two-dimensional volatility basis sets in
      simulating the aging of secondary organic aerosol with smog-chamber experiments.
AB  - We evaluate the one-dimensional volatility basis set (1D-VBS) and two-dimensional
      volatility basis set (2D-VBS) in simulating the aging of SOA derived from toluene
      and alpha-pinene against smog-chamber experiments. If we simulate the first
      generation products with empirical chamber fits and the subsequent aging
      chemistry with a 1D-VBS or a 2D-VBS, the models mostly overestimate the SOA
      concentrations in the toluene oxidation experiments. This is because the
      empirical chamber fits include both first-generation oxidation and aging;
      simulating aging in addition to this results in double counting of the initial
      aging effects. If the first-generation oxidation is treated explicitly, the base
      case 2D-VBS underestimates the SOA concentrations and O:C increase of the toluene
      oxidation experiments; it generally underestimates the SOA concentrations and
      overestimates the O:C increase of the alpha-pinene experiments. With the first
      generation oxidation treated explicitly, we could modify the 2D-VBS configuration
      individually for toluene and alpha-pinene to achieve good model-measurement
      agreement. However, we are unable to simulate the oxidation of both toluene and
      alpha-pinene with the same 2D-VBS configuration. We suggest that future models
      should implement parallel layers for anthropogenic (aromatic) and biogenic
      precursors, and that more modeling studies and laboratory research be done to
      optimize the "best-guess" parameters for each layer. 

PMID- 25581403
TI  - Plasmon-enhanced photoelectrochemical water splitting using au nanoparticles
      decorated on hematite nanoflake arrays.
AB  - Hematite nanoflake arrays were decorated with Au nanoparticles through a simple
      solution chemistry approach. We show that the photoactivity of Au-decorated Fe2
      O3 electrodes for photoelectrochemical water oxidation can be effectively
      enhanced in the UV/Visible region compared with the bare Fe2 O3 . Au-nanoparticle
      decorated Fe2 O3 nanoflake electrodes exhibit a significant cathodic shift of the
      onset potential up to 0.6 V [vs. reversible hydrogen electrode (RHE)], and a two
      times increase in the water oxidation photocurrent is achieved at 1.23 VRHE . A
      maximum photocurrent of 2.0 mA cm(-2) at 1.6 VRHE is obtained in 1 M KOH under AM
      1.5 (100 mW cm(-2) ) conditions. The enhancement in photocurrent can be
      attributed to the Au nanoparticles acting as plasmonic photosensitizers that
      increase the optical absorption. 

PMID- 25581405
TI  - Ponatinib given for advanced leukemia relapse after allo-SCT.

PMID- 25581404
TI  - Impact of Epstein Barr virus-related complications after high-risk allo-SCT in
      the era of pre-emptive rituximab.
AB  - We monitored 133 high-risk allo-SCT recipients for 6 months after transplant for
      EBV reactivation by quantitative real-time PCR. Rituximab was given as pre
      emptive therapy for viremia >1000 copies/mL. The 1-year cumulative incidence of
      EBV reactivation was 29.4% (95% confidence interval (CI): 18-40) in patients
      monitored due to initial high-risk characteristics (n=93) and 31.8% (95% CI: 19.7
      44) in those followed because of the development of refractory GVHD (n=40).
      Overall response rate to Rituximab was 83%. Nine patients (9.6%) developed post
      transplant lymphoproliferative disorder (PTLD) at a median of +62 days after SCT.
      Eight of them showed a concomitant CMV reactivation. Second SCT was the only risk
      factor associated with EBV infection and PTLD in multivariate analysis (hazard
      ratio (HR) 2.6 (95% CI: 1.1-6.4; P=0.04) and HR 6.4 (95%CI: 1.3-32; P=0.02)). The
      development of EBV reactivation was not associated with non-relapse mortality or
      OS (P=0.97 and P=0.84, respectively). 

PMID- 25581406
TI  - Engraftment syndrome: double-edged sword of hematopoietic cell transplants.
AB  - Engraftment syndrome (ES) after hematopoietic cell transplantation (HCT) is
      increasingly diagnosed. Common features include fever, pulmonary vascular leak,
      rash and organ dysfunction. Different diagnostic criteria likely account for the
      wide (7-90%) range of reported incidences. ES typically occurs within 4 days of
      granulocyte recovery although a recently described seemingly similar syndrome
      occurs >1 week before granulocyte recovery after umbilical cord blood cell
      transplants. Although the clinical manifestations of ES may be identical to those
      of acute GVHD, ES also has been well described in patients without acute GVHD.
      The data are conflicting as to whether ES is associated with a higher nonrelapse
      mortality and worse survival after HCT. The pathophysiology of ES is unclear, but
      endothelial injury and activated granulocytes in the setting of proinflammatory
      cytokines may be important. ES typically is self-limited, but, like acute GVHD,
      responds to corticosteroids. Because ES and acute GVHD may have overlapping
      features and response to therapy, these disease processes may often not be
      distinct events. Moreover, features of ES may overlap with those of drug- and
      radiation-induced toxicities and infection. Further research to better
      characterize the clinical spectrum and etiology of ES and to determine its
      relationship to GVHD is needed. 

PMID- 25581407
TI  - Tuberculosis in umbilical cord blood transplant recipients: clinical
      characteristics and challenges.

PMID- 25581408
TI  - Inadvertent transmission of occult CML through allo-SCT.

PMID- 25581409
TI  - Interpreting outcome data in hematopoietic cell transplantation for leukemia:
      tackling common biases.
AB  - Although patient outcomes after allogeneic hematopoietic cell transplantation
      (allo-HCT) have significantly improved in recent years, complications and
      associated mortality remain substantial. Although many transplants are performed
      worldwide, the number of patients enrolled prospectively into clinical trials is
      small. Patient and physician preferences often override treatment assignments in
      randomized transplant trials, biasing the common intention-to-treat analyses.
      Large retrospective and observational database studies are likely to detect the
      real effect of allo-HCT. However, they may be subject to immortal time and other
      biases derived from heterogeneity of allo-HCT indications and approaches and
      differences in referral or institutional policies affecting patient selection.
      Timing of the transplant procedure may be fundamental but studies commencing at
      start of transplant may neglect the influence of pretransplant therapies.
      Conversely, a prolonged lag period between the decision and execution of
      transplant may artificially 'improve' the outcome by 'natural' selection weeding
      out patients relapsing or dying before transplant. Finally, comparative
      nonrandomized transplantation trials often suffer from unbalanced assignment for
      therapy arms. We herein present common clinical dilemmas discussing proper
      application of available evidence in daily clinical practice. Pitfalls and
      caveats frequent in clinical studies of allo-SCT are highlighted to promote a
      balanced interpretation of available data. 

PMID- 25581410
TI  - Pegfilgrastim vs filgrastim in PBSC mobilization for autologous hematopoietic
      SCT: a systematic review and meta-analysis.
AB  - Trial outcomes comparing cytokine agents for PBSC mobilization in autologous
      hematopoietic transplant patients have been controversial. We performed a
      systematic review and meta-analysis of evidence available on pegfilgrastim vs
      filgrastim in chemo-cytokine mobilization. Electronic literature searches of
      PubMed, EMBASE and CENTRAL identified nine articles eligible for qualitative
      analysis with one randomized controlled trial. Eight articles involving 719
      patients were included in the meta-analysis. Results showed similar CD34+ cell
      collection yields for pegfilgrastim and filgrastim (SDM -0.08, 95% CI: -0.388 to
      0.228). On comparison with filgrastim, pegfilgrastim showed a significantly
      earlier apheresis onset time (SDM: -0.512, 95% CI: -0.973 to -0.050) and
      reduction in required apheresis procedures (SDM -0.260, 95% CI: -0.466 to 
      0.054). Times to leukocyte (?1.0 * 10(9)/L) and platelet (?20 * 10(9)/L) recovery
      were similar between groups (SDM: 0.015, 95% CI: -0.41 to 0.44 and SDM: 0.309,
      95% CI: -0.11 to 0.72, respectively). Both agents were well tolerated and mild
      bone pain was the most frequently reported adverse event. Pegfilgrastim may be a
      convenient alternative to filgrastim in PBSC mobilization for multiple myeloma
      and lymphoma patients, but further studies are required to clarify effects of
      cytokine dosage and previous cytotoxic exposure in specific subpopulations. 

PMID- 25581411
TI  - Focal nodular hyperplasia of the liver: an emerging complication of hematopoietic
      SCT in children.
AB  - Hepatic focal nodular hyperplasia (FNH) is a nonmalignant condition rarely
      affecting children previously treated for cancer, especially those who received
      hematopoietic SCT (HSCT). Some aspects of its pathogenesis still remain unclear
      and a strong association with specific risk factors has not yet been identified.
      We report here a single institution's case series of 17 patients who underwent
      HSCT and were diagnosed with FNH, analyzing retrospectively their clinical
      features and the radiological appearance of their hepatic lesions. We aimed to
      compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging
      (MRI) and to explore the role of transient elastography (FibroScan) to evaluate
      the degree of hepatic fibrosis in FNH patients. Our analysis showed an
      association of FNH with age at transplant ?12 years (hazard ratio (HR) 9.10);
      chronic GVHD (HR 2.99); hormone-replacement therapy (HR 4.02) and abdominal
      radiotherapy (HR 4.37). MRI proved to be a more accurate diagnostic tool compared
      with US. Nine out of 12 patients who underwent FibroScan showed hepatic fibrosis.
      Our study points out that FNH is an emerging complication of HSCT, which requires
      a lifelong surveillance to follow its course in cancer patients. 

PMID- 25581412
TI  - Correlation between microsatellite discrepancy scores and transplant outcome
      after haemopoietic SCT for pediatric ALL.
AB  - Microsatellite analyses show that self-reported ethnicity often correlates poorly
      with true genetic ancestry. As unknown ancestral differences could potentially
      have an impact on transplant outcome, we developed an average allele length
      discrepancy (AALD) score to assess allele length discrepancy between
      donor/recipient (D/R) using microsatellites analysed routinely in post-transplant
      chimeric assessment. This was then compared with outcome in a homogeneously
      treated cohort of pediatric patients undergoing high-resolution sibling or
      matched unrelated donor transplantation for acute lymphoblastic leukemia (ALL).
      AALD scores formed a numeric continuum ranging from 0 to 1.4 (median 0.76) for
      sibling pairs and 0.8-2.17 (median 1.6) for high-resolution matched unrelated
      donor (HR-MUD) pairs. There was a trend for worse OS with increasing AALD score,
      which reached statistical significance above a threshold of 1.7 for OS. Patients
      whose transplants had an AALD score of ?1.8 had a risk of non-relapse mortality
      4.9 times greater (P=0.025) and relapse risk three times greater (P=0.058) than
      those scoring <1.8. This approach will now be explored in a Centre International
      for Blood and Marrow Transplantation Research (CIBMTR) study of 750 D/R pairs
      across all disease groups; if confirmed, it has the potential to improve donor
      selection for patients with multiple prospective donors. 

PMID- 25581413
TI  - Design and inference for the intent-to-treat principle using adaptive treatment.
AB  - Nonadherence to assigned treatment jeopardizes the power and interpretability of
      intent-to-treat comparisons from clinical trial data and continues to be an issue
      for effectiveness studies, despite their pragmatic emphasis. We posit that new
      approaches to design need to complement developments in methods for causal
      inference to address nonadherence, in both experimental and practice settings.
      This paper considers the conventional study design for psychiatric research and
      other medical contexts, in which subjects are randomized to treatments that are
      fixed throughout the trial and presents an alternative that converts the fixed
      treatments into an adaptive intervention that reflects best practice. The key
      element is the introduction of an adaptive decision point midway into the study
      to address a patient's reluctance to remain on treatment before completing a full
      length trial of medication. The clinical uncertainty about the appropriate
      adaptation prompts a second randomization at the new decision point to evaluate
      relevant options. Additionally, the standard 'all-or-none' principal
      stratification (PS) framework is applied to the first stage of the design to
      address treatment discontinuation that occurs too early for a midtrial
      adaptation. Drawing upon the adaptive intervention features, we develop
      assumptions to identify the PS causal estimand and to introduce restrictions on
      outcome distributions to simplify expectation-maximization calculations. We
      evaluate the performance of the PS setup, with particular attention to the role
      played by a binary covariate. The results emphasize the importance of collecting
      covariate data for use in design and analysis. We consider the generality of our
      approach beyond the setting of psychiatric research.

PMID- 25581414
TI  - Luminescent carbon dots for logic operations in two phases.
AB  - Basic and higher integrated logic operations have been achieved by using
      luminescent carbon dots through interactions with metal ions and organic
      molecules in liquid dispersions as well as in the solid phase. The biphasic
      simple and complex logic systems could be potentially used for various analytical
      applications as well as for the detection of important elements in diverse
      environments. 

PMID- 25581415
TI  - Profiling of serum bile acids in a healthy Chinese population using UPLC-MS/MS.
AB  - Bile acids (BAs) are a group of important physiological agents for cholesterol
      metabolism, intestinal nutrient absorption, and biliary secretion of lipids,
      toxic metabolites, and xenobiotics. Extensive research in the last two decades
      has unveiled new functions of BAs as signaling molecules and metabolic regulators
      that modulate hepatic lipid, glucose, and energy homeostasis through the
      activation of nuclear receptors and G-protein-coupled receptor signaling in gut
      liver metabolic axis involving host-gut microbial co-metabolism. Therefore,
      investigation of serum BA profiles, in healthy human male and female subjects
      with a wide range of age and body mass index (BMI), will provide important
      baseline information on the BA physiology as well as metabolic homeostasis among
      human subjects that are regulated by two sets of genome, host genome, and
      symbiotic microbiome. Previous reports on age- or gender-related changes on BA
      profiles in animals and human showed inconsistent results, and the information
      acquired from various studies was highly fragmentary. Here we profiled the serum
      BAs in a large population of healthy participants (n = 502) and examined the
      impact of age, gender, and BMI on serum BA concentrations and compositions using
      a targeted metabonomics approach with ultraperformance liquid chromatography
      triple-quadrupole mass spectrometry. We found that the BA profiles were dependent
      on gender, age, and BMI among study subjects. The total BAs were significantly
      higher in males than in females (p < 0.05) and higher in obese females than in
      lean females (p < 0.05). The difference in BA profiles between male and female
      subjects was decreased at age of 50-70 years, while the difference in BA profiles
      between lean and obese increased for subjects aged 50-70 years. The study
      provides a comprehensive understanding of the BA profiles in healthy subjects and
      highlights the need to take into account age, gender, and BMI differences when
      investigating pathophysiological changes of BAs resulting from gastrointestinal
      diseases. 

PMID- 25581416
TI  - Early versus late tracheostomy for critically ill patients.
AB  - BACKGROUND: Long-term mechanical ventilation is the most common situation for
      which tracheostomy is indicated for patients in intensive care units (ICUs).
      'Early' and 'late' tracheostomies are two categories of the timing of
      tracheostomy. Evidence on the advantages attributed to early versus late
      tracheostomy is somewhat conflicting but includes shorter hospital stays and
      lower mortality rates. OBJECTIVES: To evaluate the effectiveness and safety of
      early (<= 10 days after tracheal intubation) versus late tracheostomy (> 10 days
      after tracheal intubation) in critically ill adults predicted to be on prolonged
      mechanical ventilation with different clinical conditions. SEARCH METHODS: This
      is an update of a review last published in 2012 (Issue 3, The Cochrane Library)
      with previous searches run in December 2010. In this version, we searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 8); MEDLINE
      (via PubMed) (1966 to August 2013); EMBASE (via Ovid) (1974 to August 2013);
      LILACS (1986 to August 2013); PEDro (Physiotherapy Evidence Database) at
      www.pedro.fhs.usyd.edu.au (1999 to August 2013) and CINAHL (1982 to August 2013).
      We reran the search in October 2014 and will deal with any studies of interest
      when we update the review. SELECTION CRITERIA: We included all randomized and
      quasi-randomized controlled trials (RCTs or QRCTs) comparing early tracheostomy
      (two to 10 days after intubation) against late tracheostomy (> 10 days after
      intubation) for critically ill adult patients expected to be on prolonged
      mechanical ventilation. DATA COLLECTION AND ANALYSIS: Two review authors
      extracted data and conducted a quality assessment. Meta-analyses with random
      effects models were conducted for mortality, time spent on mechanical ventilation
      and time spent in the ICU. MAIN RESULTS: We included eight RCTs (N = 1977
      participants). At the longest follow-up time available in these studies, evidence
      of moderate quality from seven RCTs (n = 1903) showed lower mortality rates in
      the early as compared with the late tracheostomy group (risk ratio (RR) 0.83, 95%
      confidence interval (CI) 0.70 to 0.98; P value 0.03; number needed to treat for
      an additional beneficial outcome (NNTB) ? 11). Divergent results were reported on
      the time spent on mechanical ventilation and no differences were noted for
      pneumonia, but the probability of discharge from the ICU was higher at day 28 in
      the early tracheostomy group (RR 1.29, 95% CI 1.08 to 1.55; P value 0.006; NNTB ?
      8). AUTHORS' CONCLUSIONS: The whole findings of this systematic review are no
      more than suggestive of the superiority of early over late tracheostomy because
      no information of high quality is available for specific subgroups with
      particular characteristics.

PMID- 25581418
TI  - Use of nucleoside analogs in patients with chronic hepatitis B in Nepal: A
      prospective cohort study in a single hospital.
AB  - AIM: There still remain many concerns about the present status of antiviral
      therapy for chronic hepatitis B in developing countries in Asia, where the
      monitoring systems of virological markers have not been well established, despite
      the high prevalence of hepatitis B virus (HBV) infection. To investigate it in
      Nepal, this prospective cohort study was conducted at the Teaching Hospital of
      Tribhuvan University in Kathmandu. METHODS: From 2007 to 2012, 65 patients were
      consecutively enrolled, 44 of whom received nucleoside analogs (NA), such as
      lamivudine (LMV), adefovir or tenofovir (TDF), on the decision of the local
      hepatologist. Virological determinations were performed in Japan, by using the
      serially collected serum samples at the Teaching Hospital. Statistical analysis
      was performed, using Mann-Whitney U-test or Fisher's exact test. RESULTS: The
      younger, especially female patients of reproductive age were more frequently
      prescribed with these NA, and an increased preference for the use of TDF was
      observed over time. However, there was insufficient follow up of the NA-treated
      patients in this cohort, and not a few patients developed emergence of NA
      resistant HBV: known resistance to LMV in 3 patients and incidental resistance to
      non-administrated NA in four patients. CONCLUSION: The results of the present
      study indicate that education for physicians as well as for infected patients
      regarding the proper use of NA, together with establishment of appropriate
      monitoring systems for virological markers, is warranted to prevent an increase
      in NA-resistant HBV infections in Nepal.

PMID- 25581417
TI  - Classification of Systemic Lupus Erythematosus: Systemic Lupus International
      Collaborating Clinics Versus American College of Rheumatology Criteria. A
      Comparative Study of 2,055 Patients From a Real-Life, International Systemic
      Lupus Erythematosus Cohort.
AB  - OBJECTIVE: The new Systemic Lupus International Collaborating Clinics (SLICC)
      2012 classification criteria aimed to improve the performance of systemic lupus
      erythematosus (SLE) classification over the American College of Rheumatology
      (ACR) 1997 criteria. However, the SLICC 2012 criteria need further external
      validation. Our objective was to compare the sensitivity for SLE classification
      between the ACR 1997 and the SLICC 2012 criteria sets in a real-life,
      multicenter, international SLE population. METHODS: We conducted a cross
      sectional observational study of patients with a clinical diagnosis of SLE
      followed at the participating rheumatology centers and registered in the
      Portuguese and Spanish national registries. The sensitivity of the 2
      classification sets was compared using McNemar's test. The sensitivity of ACR
      1997 and SLICC 2012 was further examined in 5 subgroups, defined according to
      disease duration. RESULTS: We included 2,055 SLE patients (female 91.4%, white
      93.5%, mean +/- SD age at disease onset 33.1 +/- 14.4 years, mean +/- SD age at
      SLE diagnosis 35.3 +/- 14.7 years, and mean +/- SD age at the time of the study
      47.4 +/- 14.6 years) from 17 centers. The sensitivity for SLE classification was
      higher with the SLICC 2012 than with the ACR 1997 (93.2% versus 85.6%; P <
      0.0001). Of 296 patients not fulfilling the ACR 1997, 62.8% could be classified
      with the SLICC 2012. The subgroup of patients with <=5 years since disease onset
      presented the largest difference in sensitivity between the SLICC 2012 and the
      ACR 1997 (89.3% versus 76.0%; P < 0.0001); this difference diminished with longer
      disease duration, and it was no longer significant for patients with >20 years of
      disease duration. CONCLUSION: The SLICC 2012 criteria were more sensitive than
      the ACR 1997 criteria in real-life clinical practice in SLE. The SLICC 2012
      criteria may allow patients to be classified as having SLE earlier in the disease
      course.

PMID- 25581419
TI  - Simple synthesis of smart magnetically driven fibrous films for remote
      controllable oil removal.
AB  - Inspired by the marine mussel adhesive protein, smart, magnetically controllable,
      oil adsorption nanofibrous materials were successfully fabricated in this
      research. Taking advantage of the properties of dopamine whose molecular
      structure mimics the single unit of the marine mussel adhesive protein and can be
      polymerized in alkaline solution forming a "glue" layer on many kinds of material
      surfaces, magnetic iron(II, III) oxide (Fe3O4) nanoparticles were easily and
      robustly anchored on to electrospun poly(vinylidene fluoride) fibrous films.
      After fluorination, the as-prepared hierarchical structured films exhibited
      superhydrophobicity, superoleophilicity and an excellent oil adsorption capacity
      from water. Importantly, because of the magnetically controllable property
      endowed by the Fe3O4 nanoparticles, such fibrous films act as a "smart
      magnetically controlled oil removal carrier", which effectively overcome the
      drawbacks of other in situ oil adsorbant materials and can also be easily
      recovered. This work provides a simple strategy to fabricate magnetic responsive
      intelligent oil removal materials, which will find broad applications in complex
      environment oil-water separation.

PMID- 25581420
TI  - Reversion of nitrate tolerance in rat aorta rings by freeze-dried red wine.
AB  - Chronically administered organic nitrates induce nitrate tolerance and
      endothelial dysfunction, which limit their therapeutic use. eNOS uncoupling, ROS
      over-production, aldehyde dehydrogenase-2 as well as superoxide dismutase (SOD)
      oxidative inhibition, and cGMP desensitization are thought to play an important
      role. Natural polyphenols are effective antioxidants, which might counteract the
      mechanisms leading to nitrate tolerance. The aim of this work was to verify
      whether freeze-dried (dealcoholized) red wine (FDRW) was able to revert glyceryl
      trinitrate (GTN) tolerance and endothelial dysfunction induced in rat aorta rings
      with either GTN or diethyldithiocarbamate (DETCA), an irreversible inhibitor of
      Cu/Zn SOD. GTN induced a concentration-dependent relaxation of rings pre
      contracted with phenylephrine. GTN spasmolysis was significantly reduced in rings
      pre-incubated with either GTN or DETCA. FDRW, at 2.8 ug of gallic acid
      equivalents (GAE)/mL concentration, was able to revert partially, though
      significantly, GTN-induced tolerance but not tolerance and endothelial
      dysfunction induced by DETCA. This work provides the first evidence in vitro that
      red wine components, at concentrations comparable to those achieved in human
      blood after moderate consumption of red wine, revert tolerance to nitrates with a
      mechanism possibly mediated by SOD.

PMID- 25581422
TI  - Inhibin B is lower and anti-Mullerian hormone is similar in serum of men with
      spinal cord injuries compared to controls.
AB  - Men with spinal cord injury have a unique semen profile characterized by normal
      sperm concentration but abnormally low sperm motility and viability. The purpose
      of our study was to determine if new diagnostic information could be obtained for
      this population by measuring serum concentrations of inhibin B and anti-Mullerian
      hormone. These hormones, as well as follicle stimulating hormone, luteinizing
      hormone, and testosterone, were measured in 30 men with spinal cord injury and 15
      age-matched control subjects. Serum concentrations of inhibin B and testosterone
      were significantly lower in the spinal cord injury group compared to the control
      group. A statistically significant negative relationship was observed between
      serum concentrations of inhibin B and follicle stimulating hormone in both the
      spinal cord injury group and the control group, and between inhibin B and
      luteinizing hormone in the spinal cord injury group only. A significant positive
      relationship was also observed between inhibin B and sperm concentration in the
      spinal cord injury group. Although serum concentrations of inhibin B were
      significantly lower in the spinal cord injury group than in controls, inhibin B
      and anti-Mullerian hormone serum concentrations did not provide an additional
      diagnostic tool for male infertility in this population. This is the first study
      to determine serum concentrations of inhibin B and anti-Mullerian hormone in men
      with spinal cord injury. 

PMID- 25581421
TI  - Characterization and functional studies of forkhead box protein 3(-) lymphocyte
      activation gene 3(+) CD4(+) regulatory T cells induced by mucosal B cells.
AB  - The induction of mucosal tolerance has been demonstrated to be an effective
      therapeutic approach for the treatment of allergic diseases. Our previous study
      demonstrated that Peyer's patch B cells could convert naive T cells into
      regulatory T cells (so-called Treg -of-B(P) cells); however, it is important to
      characterize this particular subset of Treg -of-B cells for future applications.
      This study aimed to investigate the role of lymphocyte activating gene 3 (LAG3)
      in mediating the regulatory function of Treg -of-B(P) cells induced by mucosal
      follicular B (FOB) cells. Microarray analysis and real-time polymerase chain
      reaction (PCR) were used to assess the gene expression pattern of Treg -of-B(P)
      cells. To evaluate the role of LAG3, the in-vitro suppressive function and the
      alleviation of airway inflammation in a murine model of asthma was assessed. Our
      data indicated that FOB cells isolated from Peyer's patches had the ability to
      generate more suppressive Treg -of-B cells with LAG3 expression, compared with
      CD23(lo) CD21(lo) B cells. LAG3 is not only a marker for Treg -of-B(P) cells, but
      also participate in the suppressive ability. Moreover, CCR4 and CCR6 could be
      detected on the LAG3(+) , not LAG3(-) , Treg -of-B(P) cells and would help cells
      homing to allergic lung. In the murine model of asthma, the adoptive transfer of
      LAG3(+) Treg -of-B(P) cells was able to sufficiently suppress T helper type 2
      (Th2) cytokine production, eosinophil infiltration and alleviate asthmatic
      symptoms. LAG3 was expressed in Treg -of-B(P) cells and was also involved in the
      function of Treg -of-B(P) cells. In the future, this particular subset of Treg 
      of-B cells might be used to alleviate allergic symptoms. 

PMID- 25581423
TI  - Singular Value Decomposition Applied to Cardiac Strain from MR Imaging for
      Selection of Optimal Cardiac Resynchronization Therapy Candidates.
AB  - PURPOSE: To use singular value decomposition (SVD) in heart failure (HF) to
      reveal primary spatiotemporal strain patterns in the left ventricle (LV), then
      develop and test a time-independent metric of cardiac dyssynchrony on the basis
      of the circumferential uniformity ratio estimate (CURE) computed with SVD (CURE
      SVD) in both a canine model of HF with or without left bundle branch block (LBBB)
      and a clinical cohort referred for cardiac resynchronization therapy (CRT).
      MATERIALS AND METHODS: The research was approved by the institutional review
      board and conformed with HIPAA requirements. All subjects provided informed
      consent. In both the canine model (n = 13) and the clinical cohort (80 CRT
      candidates; mean age, 65.2 years; range, 18.5-86.9 years), regional strains were
      derived by using cardiac magnetic resonance (MR) displacement encoding with
      stimulated echoes. CURE-SVD was compared with the standard CURE (averaged over
      systolic phases). Statistical methods included the Wilcoxon rank-sum test, Hodges
      Lehmann estimator, Bland-Altman test, multivariable logistic regression, and
      receiver operating characteristic analysis. RESULTS: In the canine model, the
      median difference in CURE-SVD (range, 0-1) for LBBB-HF group versus narrow-QRS-HF
      group (-0.40; 95% confidence interval [CI]: -0.79, -0.31) was similar to that for
      CURE (-0.43; 95% CI: -0.72, -0.34]). In 80 CRT candidates, CURE-SVD and CURE were
      highly correlated (r = 0.90; P < .0001). The multivariable model for CRT response
      with CURE-SVD demonstrated excellent performance without the need for time
      averaging over cardiac phases (area under the receiver operating characteristic
      curve = 0.96, P < .0001). CONCLUSION: SVD of circumferential strain in HF
      identifies primary LV spatiotemporal contraction patterns with minimal user
      input, while the time-independent CURE-SVD parameter has excellent performance in
      a canine model of dyssynchrony and is strongly associated with CRT response in
      patients with HF.

PMID- 25581425
TI  - Comparing the Performance Status Scale and MD Anderson Dysphagia Inventory as
      swallowing outcome measures in head and neck cancer: a prospective cohort study.
AB  - OBJECTIVES: To examine the relationship between the two disease-specific measures
      currently in use to assess swallowing outcomes following treatment in patients
      with head and neck cancer: the Performance Status Scale (PSS) and MD Anderson
      Dysphagia Inventory (MDADI). DESIGN: A prospective cohort study. SETTING: Four
      head and neck cancer multidisciplinary clinics in the North of England Cancer
      Network. PARTICIPANTS: 114 patients with cancers of the upper aerodigestive
      tract. MAIN OUTCOME MEASURE: Measures of swallowing function administered
      prospectively across 4 timepoints RESULTS: Spearman's correlation coefficients
      were used to measure the relationship between the two scales. There was
      statistically significant correlation between the two tools at pre-treatment (rs
      = 0.428, P < 0.000), 3 months post-treatment (rs = 0.454, P < 0.002), 6 months
      post-treatment (rs = 0.551, P < 0.000) and 12 months post-treatment (rs = 0.680,
      P < 0.000). CONCLUSION: This is the first prospective study comparing the MDADI
      and PSS questionnaires at multiple time points. Our study shows that these
      different instruments have a good relationship in measuring swallowing function
      in patients with head and neck cancer in short and medium term after treatment.

PMID- 25581426
TI  - Effectiveness of red clover in alleviating menopausal symptoms: a 12-week
      randomized, controlled trial.
AB  - OBJECTIVES: Menopausal women are interested in alternative therapy to alleviate
      climacteric symptoms. This study aimed to investigate the effect of red clover on
      the severity of menopausal symptoms. METHODS: This randomized, placebo
      controlled, clinical trial included 72 healthy postmenopausal women, who were
      randomly divided into intervention and placebo groups. Women in the intervention
      group received two capsules containing 40 mg dried leaves of red clover daily for
      12 weeks, while those in the control group received two capsules containing 40 mg
      starch daily for 12 weeks. Outcome measures of this study were menopausal
      symptoms determined using the Menopause Rating Scale (MRS) at baseline and at the
      end of the study. Sociodemographic data of the included women were collected
      using a questionnaire. RESULTS: No significant differences were observed between
      the two groups with respect to the demographic characteristics and menopausal
      symptoms before the intervention. At the end of the study, the total score on the
      MRS decreased from 20.41 to 10.08 in the intervention group and from 20.77 to
      17.20 in the control group. This decrease in the total score was attributed to
      the scores of vegetative somatic and psychological categories of menopausal
      symptoms. Thus, a remarkable difference was observed in the severity of the
      menopausal symptoms (95% confidence interval, p = 0.0001). CONCLUSION: These
      results indicated that, compared to placebo, dried leaves of red clover were more
      effective in reducing the severity of menopausal symptoms in postmenopausal
      women.

PMID- 25581424
TI  - Gonadotropin surge-inhibiting/attenuating factors: a review of current evidence,
      potential applications, and future directions for research.
AB  - Animal studies in the 1980s suggested the existence of an ovarian hormone, termed
      gonadotropin surge-inhibiting/attenuating factor (GnSIF/AF), that modulates
      pituitary secretion of luteinizing hormone (LH). Given the importance of
      identifying regulatory factors of the hypothalamic-pituitary-ovarian axis and the
      accumulating data suggesting its existence, we conducted a comprehensive
      literature search using PubMed, Web of Science, Scopus, and Embase to identify
      articles related to GnSIF/AF. The search generated 161 publications, of which 97
      were included in this study. Several attempts have been made to identify and
      characterize this hormone and several candidates have been identified, but the
      protein sequences of these putative GnSIF/AF factors differ widely from one study
      to another. In addition, while the RF-amide RFRP-3 is known foremost as a
      neuropeptide, some research supports an ovarian origin for this non-steroidal
      hormone, thereby suggesting a role for RFRP-3 either as a co-modulator of
      GnSIF/AF or as a gonadotropin-inhibiting factor in the hypothalamus (GnIH).
      Discovery of the KNDy neurons that modulate GnRH secretion, on the other hand,
      further encourages the search for substance(s) that modulate their activity and
      that indirectly affect LH secretion and the hypothalamic-pituitary-ovarian axis.
      While it has remained an elusive hormone, GnSIF/AF holds many potential
      applications for contraception, in vitro fertilization, and/or cancer as well as
      for understanding polycystic ovary syndrome, metabolic diseases, and/or pubertal
      development. In this review, we rigorously examine the available evidence
      regarding the existence of GnSIF/AF, previous attempts at its identification,
      limitations to its discovery, future directions of research, and potential
      clinical applications.

PMID- 25581427
TI  - Contribution of chlorophyll to photooxidation of soybean oil at specific visible
      wavelengths of light.
AB  - Photosensitizers in foods and beverages are important considerations when
      selecting packaging materials. Chlorophyll is found at low concentrations in many
      food products. The objective of this study was to determine the photosensitizing
      effect of chlorophyll on soybean oil (SO) using broad-spectrum light and 3
      visible wavelength regions of light. SO with added chlorophyll (0, 1, or 2 MUg
      chlorophyll added/mL SO) was exposed to 5 light conditions, using a photochemical
      reactor (10  degrees C; 4 h). Light treatments included broad-spectrum (BS; no
      filter; 157.6 +/- 4.7 mW intensity), 430 nm (10 nm; 1.8 +/- 0.7 mW), and 660 nm
      (10 nm; 0.332 +/- 0.05 mW) wavelengths compared to a no-light control.
      Chlorophyll a (but not b) absorbs light in the selected visible wavelength
      regions. Chlorophyll degradation was evaluated. Oxidative changes in SO were
      assessed by peroxide value (PV) and thiobarbituric acid-reactive substances
      (TBARS) assay, which measures malondialdehyde (MDA). Chlorophyll was completely
      degraded at BS and 430 nm conditions and degraded to 36% of original
      concentration at 660 nm wavelength. PV and MDA concentration significantly
      increased with chlorophyll addition (1 MUg/mL) at BS and 430 nm wavelengths
      compared to no-light control. Lower light intensity at 660 nm initiated oxidation
      reactions as measured by PV, but not significantly. There were differences in PV
      (BS, 430 nm) and TBARS (BS) between the no-light and light-exposed SO without
      chlorophyll added. There was very little effect at 450 nm. This study suggests
      that broad-spectrum light and at least light wavelengths at or near 430 nm and
      660 nm excite chlorophyll, resulting in initiation of oxidation reactions.
      Packaging material selection for foods and beverages should consider blocking
      excitation wavelengths of photosensitizing molecules, including chlorophyll, to
      protect product quality. 

PMID- 25581428
TI  - Genome-wide profiling of HPV integration in cervical cancer identifies clustered
      genomic hot spots and a potential microhomology-mediated integration mechanism.
AB  - Human papillomavirus (HPV) integration is a key genetic event in cervical
      carcinogenesis. By conducting whole-genome sequencing and high-throughput viral
      integration detection, we identified 3,667 HPV integration breakpoints in 26
      cervical intraepithelial neoplasias, 104 cervical carcinomas and five cell lines.
      Beyond recalculating frequencies for the previously reported frequent integration
      sites POU5F1B (9.7%), FHIT (8.7%), KLF12 (7.8%), KLF5 (6.8%), LRP1B (5.8%) and
      LEPREL1 (4.9%), we discovered new hot spots HMGA2 (7.8%), DLG2 (4.9%) and SEMA3D
      (4.9%). Protein expression from FHIT and LRP1B was downregulated when HPV
      integrated in their introns. Protein expression from MYC and HMGA2 was elevated
      when HPV integrated into flanking regions. Moreover, microhomologous sequence
      between the human and HPV genomes was significantly enriched near integration
      breakpoints, indicating that fusion between viral and human DNA may have occurred
      by microhomology-mediated DNA repair pathways. Our data provide insights into HPV
      integration-driven cervical carcinogenesis. 

PMID- 25581429
TI  - No evidence that selection has been less effective at removing deleterious
      mutations in Europeans than in Africans.
AB  - Non-African populations have experienced size reductions in the time since their
      split from West Africans, leading to the hypothesis that natural selection to
      remove weakly deleterious mutations has been less effective in the history of non
      Africans. To test this hypothesis, we measured the per-genome accumulation of
      nonsynonymous substitutions across diverse pairs of populations. We find no
      evidence for a higher load of deleterious mutations in non-Africans. However, we
      detect significant differences among more divergent populations, as archaic
      Denisovans have accumulated nonsynonymous mutations faster than either modern
      humans or Neanderthals. To reconcile these findings with patterns that have been
      interpreted as evidence of the less effective removal of deleterious mutations in
      non-Africans than in West Africans, we use simulations to show that the observed
      patterns are not likely to reflect changes in the effectiveness of selection
      after the populations split but are instead likely to be driven by other
      population genetic factors. 

PMID- 25581430
TI  - Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.
AB  - We report germline missense mutations in ETV6 segregating with the dominant
      transmission of thrombocytopenia and hematologic malignancy in three unrelated
      kindreds, defining a new hereditary syndrome featuring thrombocytopenia with
      susceptibility to diverse hematologic neoplasms. Two variants, p.Arg369Gln and
      p.Arg399Cys, reside in the highly conserved ETS DNA-binding domain. The third
      variant, p.Pro214Leu, lies within the internal linker domain, which regulates DNA
      binding. These three amino acid sites correspond to hotspots for recurrent
      somatic mutation in malignancies. Functional studies show that the mutations
      abrogate DNA binding, alter subcellular localization, decrease transcriptional
      repression in a dominant-negative fashion and impair hematopoiesis. These
      familial genetic studies identify a central role for ETV6 in hematopoiesis and
      malignant transformation. The identification of germline predisposition to
      cytopenias and cancer informs the diagnosis and medical management of at-risk
      individuals. 

PMID- 25581434
TI  - Developing the next generation of nurse scientists.
AB  - This article describes an undergraduate nursing research internship program in
      which students are engaged in research with a faculty mentor. Since 2002, more
      than 130 undergraduate nursing students have participated. Interns coauthored
      publications, presented papers and posters at conferences, and received awards.
      This highly successful program provides a model that can be easily replicated to
      foster the development of future nurse scientists. 

PMID- 25581435
TI  - Baby Boy Jones Interactive Case-Based Learning Activity: A Web-Delivered Teaching
      Strategy.
AB  - Faced with limited resources, nurse educators are challenged with transforming
      nursing education while preparing enough qualified nurses to meet future demand;
      therefore, innovative approaches to teaching are needed. In this article, we
      describe the development of an innovative teaching activity. Baby Boy Jones is a
      Web-delivered, case-based learning activity focused on neonatal infection. It was
      created using e-learning authoring software and delivered through a learning
      management system. 

PMID- 25581436
TI  - Nursing education progression: associate degree nursing faculty perspective.
AB  - The purpose of this survey was to examine the attitudes, influences, and
      practices of associate degree nursing (ADN) faculty in relation to advising
      students about nursing education progression. The results indicated that ADN
      faculty have a sense of moral and personal role responsibility to encourage
      students to continue their education. Deficits in faculty knowledge of program
      details and multiple demands on their time are factors that influence advising
      practices. 

PMID- 25581433
TI  - Statistical Preparedness of Master's Degree-Prepared Nurses in the Workplace.
AB  - Knowledge of statistics is essential for nurses at all degree levels and is
      needed to read and understand published research, make evidence-based decisions,
      and critically evaluate research and evaluation findings. Data are needed to
      properly quantify statistical preparedness for nurse graduates and workplace
      demands for specific types of statistics knowledge. This work describes results
      of a pilot study of surveyed master's degree-prepared nurses. Findings revealed
      several gaps between statistics education and workplace demands. 

PMID- 25581437
TI  - Institutional support for diverse populations: perceptions of Hispanic and
      african american students and program faculty.
AB  - Using the Adapted Model of Institutional Support as a framework, data were
      collected from 90 minority students, 80 faculty members, and 31 administrators
      from schools of nursing in Texas to determine perceived barriers and needed
      supports for program completion. Findings illustrate similar and differing
      perceptions of Hispanic and African American students, faculty, and program
      administrators. The data provide a baseline for making improvements and
      establishing "best practices" for minority recruitment and retention. 

PMID- 25581432
TI  - Gene expression analysis identifies global gene dosage sensitivity in cancer.
AB  - Many cancer-associated somatic copy number alterations (SCNAs) are known.
      Currently, one of the challenges is to identify the molecular downstream effects
      of these variants. Although several SCNAs are known to change gene expression
      levels, it is not clear whether each individual SCNA affects gene expression. We
      reanalyzed 77,840 expression profiles and observed a limited set of
      'transcriptional components' that describe well-known biology, explain the vast
      majority of variation in gene expression and enable us to predict the biological
      function of genes. On correcting expression profiles for these components, we
      observed that the residual expression levels (in 'functional genomic mRNA'
      profiling) correlated strongly with copy number. DNA copy number correlated
      positively with expression levels for 99% of all abundantly expressed human
      genes, indicating global gene dosage sensitivity. By applying this method to
      16,172 patient-derived tumor samples, we replicated many loci with aberrant copy
      numbers and identified recurrently disrupted genes in genomically unstable
      cancers. 

PMID- 25581438
TI  - The taunting of parentally bereaved children: an exploratory study.
AB  - This exploratory study addresses the rarely mentioned, minimally investigated
      topic of peer taunting of parentally bereaved children. It suggests that social
      support cannot be adequately conceptualized or measured on an essentially one
      dimensional scale from high to low support. The data are derived from lengthy
      semistructured transcribed research interviews of bereaved children. Using
      conservative criteria, 7 of the 35 children were found to have experienced
      direct, raw taunting about their loss. The varied forms of taunting experienced
      are described, as well as a range of victim reactions. Suggestions of foci for
      future research are presented. 

PMID- 25581439
TI  - Leaf removal and wine composition of Vitis vinifera L. cv. Nero d'Avola: the
      volatile aroma constituents.
AB  - BACKGROUND: Defoliation is a cultural practice for crop management in grapevines
      and the benefits effects have been demonstrated. Here, the influence of 'early'
      leaf removal on the quality of Nero d'Avola wines was evaluated. Particular
      attention has been given to the volatile constituents responsible for the wine
      aroma but also to the total amount of polyphenolic compounds, anthocyanins and
      flavonoids. RESULTS: 'Early' defoliation was manually applied and compared with
      non-defoliated controls. The grapes were harvested at two different ripening
      times following their technological and phenolic maturity. Statistical
      quantitative differences occurred among the samples from the four trials
      (defoliated and control samples, both at two ripening times). Both the time of
      harvest and the vine leaf removal determined variation in the wine composition. A
      large number of volatile constituents were identified and quantified; the odour
      activity values (OAVs) were calculated. Basal leaf removal reduced pH and
      increased titratable acidity, total amount of anthocyanins, flavonoids,
      polyphenols and colour intensity in the wines from the first harvest. Results
      showed the increase of fermentation and varietal aromas in the defoliated wines
      from the first harvest. Limited differences occurred between the wines from
      defoliated and control vines relative to the second harvest. Principal components
      analysis, which was applied to compounds with OAVs >= 0.5, allowed the different
      compounds to be distinguished. CONCLUSION: 'Early' leaf removal can lead to a
      positive effect on the quality of Nero d'Avola under the environmental conditions
      in which the present study was undertaken but particular attention has to be
      given to the time of grape harvest. The results also demonstrate that 'early'
      defoliation can be applied to improve wine quality in the Mediterranean region,
      where there is a concentration of rainfall during winter, and nearly arid
      conditions and high temperatures during the summer.

PMID- 25581440
TI  - Autonomic nervous system dysregulation in irritable bowel syndrome.
AB  - BACKGROUND: Autonomic nervous system (ANS) regulation may be altered in
      functional diseases, including irritable bowel syndrome (IBS), but published data
      are not clear to date. The aim of the study was to analyze ANS function in IBS
      subjects classified by Rome III criteria and healthy controls using standardized
      technique. METHODS: ANS activity was evaluated by autoregressive spectral
      analysis of RR interval and systolic arterial pressure variabilities, to obtain
      indices of sympatho-vagal modulation of the heart and of spontaneous cardiac
      baroreflex (alpha index). A symptom list was used to score 18 somatic complaints
      (score 0-180) (4SQ). Fatigue and stress were assessed through the use of a global
      scoring index (0-10). KEY RESULTS: We enrolled 41 IBS subjects (29 F, age 40 +/-
      2 years) and 42 healthy matched controls. Heart rate was higher in IBS than
      control subjects (69 +/- 2 vs 61 +/- 1; p < 0.001). The total variance of RR
      interval variability, and alpha index, were significantly lower in IBS compared
      to controls (1983.12 +/- 384.64 ms(2) vs 4184.55 +/- 649.59 ms(2) ; 18.1 +/- 2
      ms/mmHg vs 29 +/- 3 ms/mmHg; p < 0.01). The alpha index results showed an inverse
      correlation with stress scores and somatic symptoms. CONCLUSIONS & INFERENCES:
      IBS subjects display a significant reduction in alpha index, an established
      marker of cardiac baroreflex. ANS dysfunction appears to be involved in the
      pathophysiology of IBS and its assessment may open new perspectives for clinical
      management of patients suffering from IBS.

PMID- 25581442
TI  - orchard: Paternity program for autotetraploid species.
AB  - Advances in molecular marker technology have provided new opportunities to study
      the population genetics of polyploid taxa. Paternity analysis using
      microsatellite markers can be used in detection of gene flow between individuals
      and populations, in mating system analysis, to identify factors that influence
      fecundity and fertility, to identify behaviour of parent-offspring relationships
      and in the analysis of the reproductive success of different ecological groups.
      As there is no specific program for carrying out paternity analysis in tetraploid
      species, specialized software was designed for the assignment of paternity for
      autotetraploid species. orchard is a novel implementation of exclusion and
      likelihood statistics for carrying out paternity analysis of autotetraploids.
      First, the program performs an exclusion method, and then, a likelihood statistic
      is used with nonexcluded candidate fathers. Optional features include estimation
      of allele dosage of known mother trees and the estimation of pollen flow
      distances. orchard was tested using a data set of microsatellite data of Dipteryx
      odorata, a tetraploid Amazonian tree species. 

PMID- 25581441
TI  - PET of follicle-stimulating hormone receptor: broad applicability to cancer
      imaging.
AB  - Selective overexpression of follicle-stimulating hormone receptor (FSHR) inside
      the vascular endothelium of tumors has been confirmed to play critical roles in
      angiogenesis, tumor invasion, and metastases. The expression level of FSHR
      correlates strongly with the response of tumors to antiangiogenic therapies. In
      this study, an immunoPET tracer was developed for imaging of FSHR in different
      cancer types. A monoclonal antibody (FSHR-mAb) against FSHR was conjugated with S
      2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn
      NOTA) and used for subsequent (64)Cu-labeling. NOTA-FSHR-mAb preserved FSHR
      specificity/affinity, confirmed by flow cytometry measurements. (64)Cu-labeling
      was successfully conducted with decent yields (~25%) and high specific activity
      (0.93 GBq/mg). The uptake of (64)Cu-NOTA-FSHR-mAb was 3.6 +/- 0.8, 13.2 +/- 0.7,
      and 14.6 +/- 0.4 %ID/g in FSHR-positive CAOV-3 tumors at 4, 24, and 48 h
      postinjection, respectively (n = 3), significantly higher (p < 0.05) than that in
      FSHR-negative SKOV-3 tumors (2.3 +/- 1.2, 8.0 +/- 0.9, and 9.1 +/- 1.3 %ID/g at
      4, 24, and 48 h postinjection, respectively (n = 3)) except at 4 h p.i. FSHR
      relevant uptake of (64)Cu-NOTA-FSHR-mAb was also readily observed in other tumor
      types (e.g., triple-negative breast tumor MDA-MB-231 or prostate tumor PC-3).
      Histology studies showed universal FSHR expression in microvasculature of these
      four tumor types and also prominent expression in tumor cells of CAOV-3, PC-3,
      and MDA-MB-231. Correlations between tumor FSHR level and uptake of (64)Cu-NOTA
      FSHR-mAb were witnessed in this study. FSHR-specific uptake of (64)Cu-NOTA-FSHR
      mAb in different tumors enables its applicability for future cancer theranostic
      applications and simultaneously establishes FSHR as a promising clinical target
      for cancer.

PMID- 25581443
TI  - Influence of rate of force application during compression on tablet capping.
AB  - Root cause and possible processing remediation of tablet capping were
      investigated using a specially designed tablet press with an air compensator
      installed above the precompression roll to limit compression force and allow
      extended dwell time in the precompression event. Using acetaminophen-starch
      (77.9:22.1) as a model formulation, tablets were prepared by various combinations
      of precompression and main compression forces, set precompression thickness, and
      turret speed. The rate of force application (RFA) was the main factor
      contributing to the tablet mechanical strength and capping. When target force
      above the force required for strong interparticulate bond formation, the
      resultant high RFA contributed to more pronounced air entrapment, uneven force
      distribution, and consequently, stratified densification in compact together with
      high viscoelastic recovery. These factors collectively had contributed to the
      tablet capping. As extended dwell time assisted particle rearrangement and air
      escape, a denser and more homogenous packing in the die could be achieved. This
      occurred during the extended dwell time when a low precompression force was
      applied, followed by application of main compression force for strong
      interparticulate bond formation that was the most beneficial option to solve
      capping problem.

PMID- 25581444
TI  - T-cell receptors: tugging on the anchor for a tighter hold on the tumor
      associated peptide.
AB  - Although it has been shown that human tumor-associated, HLA anchor residue
      modified "heteroclitic" peptides may induce stronger immune responses than wild
      type peptides in cancer vaccine trials, it has also been shown that some T cells
      primed with these heteroclitic peptides subsequently fail to recognize the
      natural, tumor-expressed peptide efficiently. This may provide a molecular reason
      for why clinical trials of these peptides have been thus far unsuccessful. In
      this issue of the European Journal of Immunology, Madura et al. [Eur. J. Immunol.
      2015. 45: 584-591] highlight a novel twist on T-cell receptor (TCR) recognition
      of HLA-peptide complexes. Tumor-associated peptides often lack canonical anchor
      residues, which can be substituted for the optimal residue to improve their
      antigenicity. T-cell cross-reactivity between the natural and modified
      (heteroclitic) peptides is essential for this approach to work and depends on
      whether the anchor residue substitution influences peptide conformation. The
      Melan-A/MART-126-35 peptide epitope is an example where T cells can make this
      distinction, with the natural peptide stimulating higher affinity CD8(+) T cells
      than the heteroclitic peptide, despite the heteroclitic peptide's more stable
      association with HLA-A2. The molecular basis for peptide discrimination is
      identified through the structure of the TCR bound to the natural peptide; TCR
      engagement of the natural peptide "lifts" its amino-terminus partly away from the
      HLA peptide binding groove, forming a higher affinity interface with the TCR than
      is formed with the anchor residue "optimized" heteroclitic peptide, which cannot
      be "pulled" from the HLA groove. 

PMID- 25581445
TI  - The Halophyte Cakile maritima Reduces Phenanthrene Phytotoxicity.
AB  - In a previous study, we showed that the halophyte plant model Thellungiella
      salsuginea was more tolerant to phenanthrene (Polycyclic Aromatic Hydrocarbon:
      PAH) than its relative glycophyte Arabidopsis thaliana. In the present work, we
      investigated the potential of another halophyte with higher biomass production,
      Cakile maritma, to reduce phenanthrene phytotoxicity. Sand was used instead of
      arable soil with the aim to avoid pollutant degradation by microorganisms or
      their interaction with the plant. After 6 weeks of treatment by 500 ppm
      phenanthrene (Phe), stressed plants showed a severe reduction (-73%) in their
      whole biomass, roots being more affected than leaves and stems. In parallel,
      Guaiacol peroxidase (GPX) activity was increased by 185 and 62% in leaves and
      roots, respectively. Non-enzymatic antioxidant capacity (assayed by ABTS test)
      was maintained unchanged in all plant organs. The model halophytic plant
      Thellungiella salsuginea was used as a biomarker of phenanthrene stress severity
      and was grown at 0 (control), 125, 250, and 375 ppm. T. salsuginea plants grown
      on the sand previously contaminated by 500 ppm Phe then treated by C. maritma
      culture (phytoremediation culture) showed similar biomass production as plants
      subjected to 125 ppm Phe. This suggests that the phytotoxic effects of
      phenanthrene were reduced by 75% by the 6-week treatment by C. maritima. Our
      findings indicate that C. maritima can constitute a potentially good candidate
      for PAH phytoremediation.

PMID- 25581446
TI  - An audit of anesthesia safety in a pediatric cochlear implantation program.
AB  - BACKGROUND: Approximately 50 children per year undergo cochlear implant surgery
      under the Scottish Cochlear Implant Programme at University Hospital Crosshouse,
      Kilmarnock. Many have significant comorbidities. Although this district general
      hospital has a high dependency unit, there is no pediatric intensive care unit
      (PICU). Children deemed likely to need PICU care are operated on at the local
      tertiary pediatric hospital in Glasgow, 25 miles away. OBJECTIVE: To determine
      the safety of anesthesia for cochlear implant surgery in children at a district
      general hospital. METHODS: Using the theater management system, we identified 306
      cochlear implant procedures in children aged 16 years and under. A retrospective
      case note review was performed to determine demographic data and seek evidence of
      any anesthesia-related complications. RESULTS: Records for 168 children having
      258 cochlear implant procedures were obtained. Forty percent of these children
      had one or more comorbidities, including 11.9% who were ex-premature babies.
      Twenty-two complications or incidents were noted, the majority of which were
      minor. Two cases had potentially serious complications and one of these was
      abandoned. This gives a serious complication rate of 0.8%. Undeclared upper
      respiratory tract infections was most likely the greatest preventable cause of
      complications. Seven cases were referred to the regional pediatric center during
      the study period. CONCLUSION: Anesthesia for cochlear implants in children can be
      safely carried out in a district general hospital setting. Appropriate safeguards
      should be in place to refer complex cases which may require PICU to a tertiary
      pediatric center.

PMID- 25581448
TI  - Supporting youth grieving the dying or death of a sibling or parent:
      considerations for parents, professionals, and communities.
AB  - PURPOSE OF REVIEW: The aim of this article is to highlight considerations for
      parents, professionals, and communities regarding supporting children and
      adolescents who are grieving the dying or death of a parent or sibling. RECENT
      FINDINGS: Current research is directly engaging the voices of youth who have
      experienced a parent or sibling's death. Although there continues to be much
      evidence about the distressing effect of such deaths on children and adolescents,
      there is a welcome emerging tendency to distinguish between adaptive and
      maladaptive grief. Although the literature strongly encourages parents to take an
      open and honest approach to supporting youth prior to a death, many barriers
      remain to them doing so. The literature identifies healthcare providers as being
      ideally positioned to provide guidance to families around best practice in the
      area of preparing youth for the death of a parent or sibling. Following a death,
      there is now encouraging evidence regarding the efficacy of certain interventions
      for bereaved youth, both in the short and long term, which is an important
      development in the field. SUMMARY: Youth benefit from being involved in open and
      honest conversations about a family member's cancer diagnosis, treatment,
      prognosis, and end-of-life care. Although advances are being made with regard to
      understanding the grief experience of youth, there remains a wide gap between the
      current theoretical knowledge and the availability of practical well informed
      support for grieving youth.

PMID- 25581447
TI  - Palliative and end-of-life care issues in chronic kidney disease.
AB  - PURPOSE OF REVIEW: Patients with progressive chronic kidney disease (CKD) have
      high morbidity, mortality, and symptom burden. Cardiovascular disease (CVD) and
      congestive heart failure (CHF) often contribute to these burdens and should be
      considered when providing recommendations for care. This review aims to summarize
      recent literature relevant to the provision of palliative and end-of-life care
      for patients with progressive CKD and specifically highlights issues relevant to
      those with CVD and CHF. RECENT FINDINGS: Dialysis may not benefit older, frail
      patients with progressive CKD, especially those with other comorbidities.
      Patients managed conservatively (i.e., without dialysis) may live as long as
      patients who elect to start dialysis, with better preservation of function and
      quality of life and with fewer acute care admissions. Decisions regarding
      dialysis initiation should be made on an individual basis, keeping in mind each
      patient's goals, comorbidities, and underlying functional status. Conservative
      management of progressive kidney disease is frequently not offered but is likely
      to benefit many older, frail patients with comorbidities such as CHF and CVD.
      SUMMARY: A palliative approach to the care of many patients with progressive CKD
      is essential to ensuring they receive appropriate quality care.

PMID- 25581449
TI  - Desire for hastened death: exploring the emotions and the ethics.
AB  - PURPOSE OF REVIEW: As we approach the end of our lives, many of us will have a
      desire for hastened death (DHD). Fortunately, our ability to respond to suffering
      at the end of life is improving. At the same time, in many jurisdictions, changes
      are underway to legislate physician-assisted death. This compels us as clinicians
      to explore DHD in a compassionate way - to reduce suffering and reduce premature
      death. This challenge is becoming more compelling as a large cohort of
      individuals, who value autonomy and control, age and experience illness. RECENT
      FINDINGS: Studies confirm that DHD is not always a request to die. Clarifying the
      intention behind the desire and exploring the individual factors and underlying
      reasons behind the wish have been described. Another theme questions our basic
      assumptions about these statements - a normal part of a human experience or an
      indicator of disease. This tension is also manifested in the appropriate balance
      between patient autonomy and preventing harm. SUMMARY: We have a professional
      responsibility to mindfully explore with the patient the suffering that can be
      relieved and the suffering that remains.

PMID- 25581450
TI  - Heart failure and palliative care: training needs assessment to guide priority
      learning of multiprofessionals working across different care settings.
AB  - PURPOSE OF REVIEW: International bodies acknowledge that palliative care
      principles and access to palliative care services should be offered to persons
      living with and dying from advanced illness such as heart failure. Without an
      appropriately trained workforce, however, appropriate goals of care and
      associated reductions in hospital utilizations may not be feasible.Marie Curie
      Cancer Care, British Heart Foundation Scotland and NHS Greater Glasgow and Clyde
      are working in partnership to improve the quality and access to palliative care
      for patients and their caregivers living with and dying from advanced heart
      failure. A training needs assessment has been undertaken as part of this
      programme in order to inform the development of training specific to heart
      failure and palliative care. RECENT FINDINGS: The results of the training needs
      assessment showed that the majority of respondents had some level of training
      needs to underpin their existing knowledge and skills in relation to palliative
      care, heart failure or both. SUMMARY: Well trained professionals will improve the
      coordination, earlier identification, quality of care provision and communication
      between all stakeholders. In doing so, the opportunity to facilitate preferred
      care wishes and preferred place of care for patients and families is optimised.
      Without this aligning, clinical practice with national guidance is not feasible.

PMID- 25581451
TI  - Improving the quality of end-of-life discussions.
AB  - PURPOSE OF REVIEW: This article provides an update on the recent research and
      evidence regarding quality in end-of-life (EOL) discussions with a focus on the
      care of a person with cancer. RECENT FINDINGS: Clinicians have the challenging
      task of customizing the information exchange that occurs during an EOL
      discussion. Patients identify important stipulations that accompany a desire for
      frank EOL discussions. These include timing of the discussion, ensuring
      evaluation of readiness to engage in the EOL discussion, and being invited to
      participate. The timing of an EOL discussion is likely to be more important than
      the setting in which an EOL discussion occurs. Less than 1 month prior to a
      person's death is likely to be an inadequate amount of time to allow a patient to
      consider and reflect on his or her EOL preferences. Among those admitted to the
      hospital, delay in the timing of EOL discussions carries the risk of losing
      decision-making capacity. SUMMARY: There is greater use of quality metrics as
      patient outcomes among studies examining EOL discussions. System-wide approaches
      to improving EOL discussions should include standardized documentation templates
      that are widely accessible in electronic medical records.

PMID- 25581452
TI  - Palliative and supportive care needs of heart failure patients in Africa: a
      review of recent developments.
AB  - PURPOSE OF REVIEW: Despite the rising prevalence of heart failure in Africa, it
      remains unclear what supportive and palliative care services are required to meet
      patient needs. This review highlights recent contributions to knowledge of the
      supportive and palliative care needs of heart failure patients in Africa. RECENT
      FINDINGS: Multiple epidemiological studies demonstrate the population-level
      burden of heart failure in Africa, characterized by low levels of ischaemic heart
      disease and a young mean patient age. However, few studies have addressed
      patients' specific palliative and supportive care needs. Only one recent
      published study investigated the quality of life of heart failure patients in
      Africa, and although conference abstracts suggest more research is forthcoming,
      these remain scarce. For service implementation, research is again sparse, but
      promising recent developments, including a hospital-based palliative care service
      for organ failure patients and a community-based programme to diagnose and manage
      heart failure, present future research avenues. SUMMARY: Despite advances in
      epidemiological knowledge, very little research has investigated the illness
      experience and multidimensional needs of individuals. Obtaining this evidence
      through culturally sensitive research is essential to future development and
      testing of new and existing palliative care services for heart failure patients
      in Africa. VIDEO ABSTRACT: http://links.lww.com/COSPC/A9

PMID- 25581453
TI  - Existential distress among healthcare providers caring for patients at the end of
      life.
AB  - PURPOSE OF REVIEW: Existential distress is well documented among patients at end
      of life (EOL) and increasingly recognized among informal caregivers. However,
      less information is known about existential concerns among healthcare providers
      working with patients at EOL, and the impact that such concerns may have on
      professionals. RECENT FINDINGS: Recent literature documents five key existential
      themes for professionals working in EOL care: (1) opportunity for introspection;
      (2) death anxiety and potential to compromise patient care; (3) risk factors and
      negative impact of existential distress; (4) positive effects such as enhanced
      meaning and personal growth; and (5) the importance of interventions and self
      care. SUMMARY: EOL work can be taxing, yet also highly rewarding. It is critical
      for healthcare providers to make time for reflection and prioritize self-care in
      order to effectively cope with the emotional, physical, and existential demands
      that EOL care precipitates.

PMID- 25581454
TI  - Understanding death with limited experience in life: dying children's and
      adolescents' understanding of their own terminal illness and death.
AB  - PURPOSE OF REVIEW: An up-to-date summary of the literature on children's and
      adolescents' understanding of their own terminal illness and death. RECENT
      FINDINGS: Clinicians still find it difficult to speak with pediatric patients
      about death even though guidelines for facilitating communication on the topic
      exist. As a result, pediatric patients are less likely to develop a clear
      understanding of their illness and there is a disconnect between clinicians and
      parents about prognosis, even when clinicians have concluded there is no longer
      possibility for cure. Insufficient communication and poor understanding may
      increase the risk of patients feeling isolated, mistrustful and anxious, and
      deprive them of a role model who can communicate about painful issues or share
      difficult feelings. Despite these complexities, young people often show
      remarkable resiliency in the face of death and want to get the most out of the
      remaining time they have. SUMMARY: In addition to these most recent findings,
      this review examines the challenges in researching this topic, obstacles to
      patients receiving information about prognosis, and how physical symptoms affect
      patients' ability to develop an understanding. It also reviews sources of insight
      into pediatric patients' understanding including the development of concepts of
      death, fears about their own death, legal interpretations of what patients
      understand, and how terminally ill young people continue to treasure life. It
      concludes by addressing ways clinicians can use the knowledge we have to
      communicate well with dying children and adolescents and their families.

PMID- 25581455
TI  - MUC5B promoter polymorphism in Japanese patients with idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND AND OBJECTIVE: A single nucleotide polymorphism (SNP) rs35705950 in
      the promoter of Mucin 5B (MUC5B) has been reported to be associated with
      idiopathic pulmonary fibrosis (IPF) mainly in Caucasian populations. This study
      was conducted to confirm the association between rs35705950 and IPF in a Japanese
      population. METHODS: Genomic DNA was extracted from blood samples in 384 Japanese
      and 137 German subjects, and rs35705950 was detected by commercially available
      genotyping assay. RESULTS: The genotype distributions of rs35705950 in Japanese
      patients with IPF, nonspecific interstitial pneumonia (NSIP) and healthy subjects
      (HS) were significantly different from those in the German counterparts (P <
      0.001, P < 0.001 and P = 0.010, respectively). The rs35705950 T allele
      frequencies in patients with IPF, NSIP and HS were 3.4%, 1.7% and 0.8%,
      respectively in the Japanese, while they were 33.1%, 27.4% and 4.3%, respectively
      in the German cohort. The T allele frequencies in patients with IPF were
      significantly higher than those in HS both in the Japanese (P = 0.031) and German
      (P < 0.001) cohorts. CONCLUSIONS: The association between rs35705950 and IPF was
      also present in this Japanese cohort, but was not as strong as the German
      counterpart. To our knowledge, this is the first study to successfully validate
      the association between rs35705950 and IPF in a Japanese ethnicity.

PMID- 25581456
TI  - Multi-country retrospective observational study of the management and outcomes of
      patients with Type 2 diabetes during Ramadan in 2010 (CREED).
AB  - AIM: To describe the characteristics and management of patients with diabetes who
      chose to fast during Ramadan in 2010. METHODS: This was a multi-country,
      retrospective, observational study, supplemented with physician and patient
      questionnaires, with data captured before, during and after Ramadan. A total of
      508 physicians in 13 countries enrolled 3777 patients and a total of 3394
      evaluable cases were analysed. We report on the subset of patients with Type 2
      diabetes, which included 3250 patients (95.8%). RESULTS: Oral anti-hyperglycaemic
      therapy was the predominant pre-Ramadan therapy for most patients (76.6%). The
      treatment regimen was modified before Ramadan for 39.3% of all patients (34.9%
      for patients on oral drugs alone, 47.1% for patients on injectable drugs alone).
      Almost all physicians (96.2%) reported providing fasting-specific advice to
      patients and 62.6% report using guidelines or recommendations for the management
      of diabetes during Ramadan. In all, 64% of patients reported fasting everyday of
      Ramadan and 94.2% fasted for at least 15 days. CONCLUSIONS: Physicians have
      increasingly adopted multiple approaches to the management of fasting during
      Ramadan, including the adoption of international and/or national guidelines,
      providing fasting-specific advice and adjusting treatment regimens, such that
      patients are able to fast for a greater number of days without acute
      complications. Additional research is needed to explore physician and patient
      beliefs and practices to inform the evidence-based management of diabetes while
      fasting, both during and outside of Ramadan, and to identify and address barriers
      to the universal uptake of techniques to facilitate that management.

PMID- 25581457
TI  - Increased risk of salivary gland cancer among women with a previous cancer
      diagnosis.
AB  - BACKGROUND: The purpose of this study was to evaluate salivary gland cancer
      incidence among patients with a previous cancer diagnosis and explore the
      potential relationship of salivary gland cancer among women with a previous
      diagnosis of breast cancer. METHODS: We obtained information from the
      Surveillance, Epidemiology, and End Results (SEER) database for patients
      diagnosed between 1973 and 2011. Incidence, annual percent change (APC), and
      survival were examined. RESULTS: Women were more likely than men to experience
      subsequent salivary gland cancer, female observed to expected (O/E) = 1.63 (95%
      confidence interval [CI], 1.49-1.78) versus male O/E = 1.34 (95% CI, 1.25-1.44).
      Index breast cancer does not confer greater risk of salivary gland cancer. Women
      demonstrate improved overall survival (OS) and cause-specific survival (CSS)
      compared with men for subsequent salivary gland cancer. CONCLUSION: Among
      patients with a previous cancer diagnosis, the risk of subsequent salivary gland
      cancer is greater among women than men. More research is needed to determine the
      relationship between index breast cancer and subsequent salivary gland cancer
      risk. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E446-E451, 2016.

PMID- 25581458
TI  - Correction: Breaking of the Bancroft rule for multiple emulsions stabilized by a
      single stimulable polymer.
AB  - Correction for 'Breaking of the Bancroft rule for multiple emulsions stabilized
      by a single stimulable polymer' by L. Besnard et al., Soft Matter, 2014, 10, 7073
      7087. 

PMID- 25581459
TI  - Structural conservation of chemotaxis machinery across Archaea and Bacteria.
AB  - Chemotaxis allows cells to sense and respond to their environment. In Bacteria,
      stimuli are detected by arrays of chemoreceptors that relay the signal to a two
      component regulatory system. These arrays take the form of highly stereotyped
      super-lattices comprising hexagonally packed trimers-of-receptor-dimers networked
      by rings of histidine kinase and coupling proteins. This structure is conserved
      across chemotactic Bacteria, and between membrane-bound and cytoplasmic arrays,
      and gives rise to the highly cooperative, dynamic nature of the signalling
      system. The chemotaxis system, absent in eukaryotes, is also found in Archaea,
      where its structural details remain uncharacterized. Here we provide evidence
      that the chemotaxis machinery was not present in the last archaeal common
      ancestor, but rather was introduced in one of the waves of lateral gene transfer
      that occurred after the branching of Eukaryota but before the diversification of
      Euryarchaeota. Unlike in Bacteria, the chemotaxis system then evolved largely
      vertically in Archaea, with very few subsequent successful lateral gene transfer
      events. By electron cryotomography, we find that the structure of both membrane
      bound and cytoplasmic chemoreceptor arrays is conserved between Bacteria and
      Archaea, suggesting the fundamental importance of this signalling architecture
      across diverse prokaryotic lifestyles. 

PMID- 25581460
TI  - Modulation of Alzheimer's Abeta protofilament-membrane interactions by lipid
      headgroups.
AB  - The molecular pathogenesis of Alzheimer's disease (AD) is complex and sparsely
      understood. The relationship between AD's amyloid beta (Abeta) peptides and
      neuronal membranes is central to Abeta's cytotoxicity and is directly modulated
      by the composition of the lipid headgroups. Molecular studies of the insertion of
      model Abeta40 protofilaments in lipid bilayers revealed strong interactions that
      affect the structural integrity of both the membranes and the ordered amyloid
      aggregates. In particular, electrostatics plays a crucial role in the interaction
      between Abeta protofilaments and palmytoil-oleoyl-phosphatidylethanolamine (POPE)
      lipids, a common component of neuronal plasma membranes. Here, we use all-atom
      molecular dynamics and steered molecular dynamics simulations to systematically
      compare the effects that POPE and palmytoil-oleoyl-phosphatidylcholine (POPC)
      headgroups have on the Abeta-lipid interactions. We find that Abeta
      protofilaments exhibit weaker electrostatic interactions with POPC headgroups and
      establish significantly shorter-lived contacts with the POPC bilayer. This
      illustrates the crucial yet complex role of electrostatic and hydrogen bonding
      interactions in modulating the anchoring and insertion of Abeta peptides into
      lipid bilayers. Our study reveals the atomistic details behind the barrier
      created by the lipid headgroup region in impeding solution-aggregated fibrillar
      oligomers to spontaneously insert into POPC bilayers, in contrast to the POPE
      case. While the biological reality is notoriously more complex (e.g., including
      other factors such as cholesterol), our results evidence a simple experimentally
      and computationally testable case for probing the factors that control the
      insertion of Abeta oligomeric aggregates in neuronal cell membranes--a process
      central to their neurotoxicity.

PMID- 25581461
TI  - Multiparameter flow cytometry provides independent prognostic information in
      patients with suspected myelodysplastic syndromes: A study on 804 patients.
AB  - Diagnosis of myelodysplastic syndromes (MDS) relies on well-defined
      cytomorphologic criteria but is challenging in a significant number of patients.
      The detection of aberrant antigen expression by multiparameter flow cytometry
      (MFC) is considered a promising tool to improve MDS diagnostics. We prospectively
      analyzed 804 unselected patients sent with suspected MDS for correlation of MFC
      findings with overall survival (OS) in the context of cytomorphologic and
      cytogenetic findings. Patients with evidence of MDS by MFC had a significantly
      worse OS as compared to those without (OS at 2 years, 71.2% vs. 89.4%; P<0.001).
      The number of aberrantly expressed antigens as a continuous variable was
      significantly associated with OS [P<0.001, hazards ratio (HR): 1.19 per
      additional aberrantly expressed antigen]. Multivariate analysis proved a
      diagnosis of MDS by MFC to be independently associated with OS (P=0.050; HR:
      1.42). Furthermore, a diagnosis of MDS by MFC was related to inferior survival
      within all three cytomorphologically defined subgroups, i.e., proven MDS (median
      OS, 45.4 vs. 52.8 months, P<0.001), suspected MDS (2-year-OS, 75.0% vs. 82.8%;
      P=0.062), and MDS excluded (2-year-OS, 63.5% vs. 92.8%, P=0.020). Our data
      clearly demonstrate that, in the assessment of cytopenic patients with suspected
      MDS, a diagnosis of MDS by MFC is independently associated with OS, which had
      been shown in previous studies for today's standard diagnostic parameters
      cytomorphology and cytogenetics. MFC may, therefore, be considered an additional
      tool in the diagnostic workup of patients with suspected MDS.

PMID- 25581463
TI  - The influence of BMI and predictors of disordered eating and life satisfaction on
      postmenopausal women.
AB  - This study aims to compare eating behaviors, body satisfaction, exercise, and
      life satisfaction between normal-weight and overweight postmenopausal women and
      to examine the predictors of disordered eating and life satisfaction among
      postmenopausal women (n = 294). The overweight group had more eating disordered
      behavior, more body dissatisfaction, and lower physical quality of life. The
      increase of age predicted less disordered eating. Higher BMI, the perception of
      an ideal weight lower than the current one, lower body satisfaction, and physical
      quality of life predicted disordered eating. Higher body satisfaction, less
      psychosocial discomfort, and a greater degree of sexual symptom discomfort
      predicted life satisfaction. 

PMID- 25581462
TI  - Relationship characteristics and contraceptive use among dating and cohabiting
      young adult couples.
AB  - CONTEXT: Contraceptive decision making occurs in the context of relationships.
      Although many individual-level characteristics have been linked to youths'
      contraceptive use, less is known about associations between contraceptive use and
      relationship-level characteristics. METHODS: Data from the 2001-2002 romantic
      pair subsample of the National Longitudinal Study of Adolescent Health were used
      to describe characteristics of 322 dating relationships and 406 cohabiting
      relationships among young adults aged at least 18 years. Logistic regression was
      employed to assess associations between these characteristics and hormonal or
      long-acting contraceptive use and condom use. Data from both partners allowed
      discordance in reports between partners in some measures to be examined. RESULTS:
      Cohabiting couples were less likely than dating couples to have used condoms (19%
      vs. 37%) and hormonal or long-acting methods (40% vs. 57%) at last sex. In dating
      relationships, couples reporting discordant levels of intimacy and couples in
      which neither partner reported a high level of intimacy had greater odds of
      condom use than couples in which both partners reported high intimacy (odds
      ratios, 4.5 and 3.3, respectively); mistrust and male problem drinking were
      negatively associated with condom use (0.3 for each). For cohabiting couples,
      frequency of sex was negatively associated with condom use and hormonal method
      use (0.8 for each). CONCLUSIONS: At least for dating couples, contraceptive use
      is linked to multiple dimensions of relationships, particularly measures
      reflecting relationship quality-both positive and negative.

PMID- 25581465
TI  - Correction to salmon et Al. (2014).
AB  - Reports an error in "Does adding an emotion component enhance the Triple P
      Positive Parenting Program" by Karen Salmon, Cassandra Dittman, Matthew Sanders,
      Rebecca Burson and Josie Hammington (Journal of Family Psychology, 2014[Apr], Vol
      28[2], 244-252). In the article, a disclaimer was inadvertently omitted from the
      author note. The disclaimer has been included. (The following abstract of the
      original article appeared in record 2014-07166-001.) This pilot study aimed to
      compare the efficacy of a regular offering of the group-delivered Triple P
      Positive Parenting Program for child behavior problems with an enhanced version
      tailored to promote child emotion competence. Families of children between ages 3
      and 6 years displaying early-onset conduct problems were randomly assigned to
      Group Triple P (GTP; final n = 18) or Emotion Enhanced Triple P (EETP; final n =
      18), in which parents were encouraged to incorporate emotion labels and causes
      and to coach emotion competence during discussions of everyday emotional
      experiences with their child. Compared with parents who received GTP, parents who
      received EETP increased their discussion of emotion labels and emotion causes in
      conversations with their child at postintervention, but this advantage was lost
      by the 4-month follow-up. Parents in the EETP condition also used more emotion
      coaching postintervention and at follow-up. There were no differences at
      postintervention or follow-up in children's emotion knowledge skills.
      Postintervention improvement in disruptive child behavior was greater for GTP,
      but the groups converged at follow-up. Parents were similarly satisfied with both
      interventions. Overall, EETP showed little advantage over regular GTP delivery.
      (PsycINFO Database Record (c) 2015 APA, all rights reserved). 

PMID- 25581466
TI  - Correction to sanders (2008).
AB  - Reports an error in "Triple P-Positive Parenting Program as a public health
      approach to strengthening parenting" by Matthew R. Sanders (Journal of Family
      Psychology, 2008[Aug], Vol 22[4], 506-517). In the article, a disclaimer was
      inadvertently omitted from the author note. The disclaimer has been included.
      (The following abstract of the original article appeared in record 2008-10898
      003.) Parenting programs have considerable potential to improve the mental health
      and well-being of children, improve family relationships, and benefit the
      community at large. However, traditional clinical models of service delivery
      reach relatively few parents. A public health approach is needed to ensure that
      more parents benefit and that a societal-level impact is achieved. The Triple P
      Positive Parenting Program is a comprehensive, multilevel system of parenting
      intervention that combines within a single intervention universal and more
      targeted interventions for high-risk children and their parents. With Triple P,
      the overarching goal is to enhance the knowledge, skills, and confidence of
      parents at a whole-of-population level and, in turn, to reduce the prevalence
      rates of behavioral and emotional problems in children and adolescents. The
      distinguishing features of the intervention and variables that influence its
      effective implementation are discussed. Self-regulation is a unifying concept
      that is applied throughout the entire system (e.g., to interactions between
      children, parents, service providers, and agencies involved in delivering the
      intervention). Challenges and future directions for the development of public
      health approaches to parenting are discussed. (PsycINFO Database Record (c) 2015
      APA, all rights reserved). 

PMID- 25581464
TI  - Human X-DING-CD4 mediates resistance to HIV-1 infection through novel paracrine
      like signaling.
AB  - X-DING-CD4 is a novel phosphatase mediating antiviral responses to HIV-1
      infection. This protein is constitutively expressed and secreted by HIV-1
      resistant CD4(+) T cells and its mRNA transcription is up-regulated in peripheral
      blood mononuclear cells from HIV-1 elite controllers. The secreted/soluble X-DING
      CD4 protein form is of particular importance because it blocks virus
      transcription when added to HIV-1 susceptible cells. The present study aimed to
      determine the contribution of this factor to the induction of the antiviral
      response in target cells. We found that soluble X-DING-CD4 enters cells by
      endocytosis and that influx of this protein induced transcription of interferon
      alpha and endogenous X-DING-CD4 mRNA in transformed CD4(+) T cells and primary
      macrophages. Treatment of HIV-1 susceptible cells with exogenous X-DING-CD4
      caused depletion of phosphorylated p50 and p65 nuclear factor kappa beta subunits
      and a significant reduction in p50/p65 nuclear factor kappa beta binding to the
      HIV-1 long terminal repeat. Taken together, these findings indicate a novel
      antiviral mechanism mediated by the influx of soluble X-DING-CD4, its signaling
      to promote self-amplification, and functional duality as an endogenous innate
      immunity effector and exogenous factor regulating gene expression in bystander
      cells.

PMID- 25581468
TI  - Correction to dittman et Al. (2014).
AB  - Reports an error in "Predicting success in an online parenting intervention: The
      role of child, parent, and family factors" by Cassandra K. Dittman, Susan P.
      Farruggia, Melanie L. Palmer, Matthew R. Sanders and Louise J. Keown (Journal of
      Family Psychology, 2014[Apr], Vol 28[2], 236-243). In the article, disclaimer was
      inadvertently omitted from the author note. The disclaimer is included. (The
      following abstract of the original article appeared in record 2014-08130-001.)
      The present study involved an examination of the extent to which a wide range of
      child, parent, family, and program-related factors predicted child behavior and
      parenting outcomes after participation in an 8-session online version of the
      Triple P-Positive Parenting Program. Participants were mothers and fathers of 97
      children aged between 3 and 8 years displaying elevated levels of disruptive
      behavior problems. For both mothers and fathers, poorer child behavior outcomes
      at postintervention were predicted by the number of sessions of the intervention
      completed by the family. For mothers, postintervention child behavior was also
      predicted by the quality of the mother-child relationship at baseline; for
      fathers, baseline child behavior severity was an additional predictor. Mothers'
      postintervention ineffective parenting was predicted by session completion and
      preintervention levels of ineffective parenting, whereas the only predictor of
      fathers' ineffective parenting at postintervention was preintervention levels of
      ineffective parenting. Socioeconomic risk, parental adjustment, and father
      participation in the intervention were not significant predictors of mother- or
      father-reported treatment outcomes. The implications of the findings for the
      provision of online parenting support are discussed. (PsycINFO Database Record
      (c) 2015 APA, all rights reserved). 

PMID- 25581467
TI  - Coparenting and children's temperament predict firstborns' cooperation in the
      care of an infant sibling.
AB  - This study examined how coparenting and firstborn children's temperament
      predicted children's cooperative behavior in response to maternal requests for
      assistance in the care of a 1-month-old infant sibling. Children's cooperative
      responding was observed during a diaper change session for 216 firstborns (ages
      13 to 70 months; M = 32). Parents also completed questionnaires assessing
      coparenting and children's temperament. Results suggested that coparenting
      quality moderated the association between children's temperament (i.e.,
      soothability) and children's cooperation as revealed in a Temperament *
      Cooperative Coparenting * Undermining Coparenting interaction. Specifically, low
      soothability predicted low levels of children's cooperation in families with high
      undermining and low cooperative coparenting, over and above the effects of child
      age, gender, and mothers' education. Findings further our understanding of how
      temperamental characteristics and coparenting quality conjointly predict
      individual differences in firstborn children's positive adjustment across the
      transition to siblinghood.

PMID- 25581469
TI  - Normal bacterial conjunctival flora in the Huacaya alpaca (Vicugna pacos).
AB  - OBJECTIVE: To describe the bacterial flora of the normal conjunctiva of Huacaya
      alpacas (Vicugna pacos) and to determine the effect of age and gender on this
      flora. ANIMALS STUDIED: Fifty Huacaya alpacas. PROCEDURES: After a complete
      ophthalmic examination, conjunctival swabs were obtained from both eyes and
      cultured for aerobic and anaerobic bacteria. Logistic and Poisson regression
      analyses were used to evaluate the effect of age and gender on bacterial
      isolation. RESULTS: Four animals were excluded because of signs of external
      ocular disease. Of the remaining 46 alpacas, bacteria were recovered from 96.7%
      (89/92) of the eyes. A total of 190 bacterial isolates were cultured with a mean
      of 2.1 bacterial isolates per eye. The majority of isolates (70%) were Gram
      positive. Staphylococcus xylosus (44/190: 23.2%) predominated, followed by
      viridans streptococci (32/190: 16.8%) and Pantoea agglomerans (24/190: 12.6%).
      Other frequently isolated bacteria included Rothia mucilaginosa (12/190: 6.3%),
      Staphylococcus equorum (12/190: 6.3%), Bacillus species (9/190: 4.7%), Moraxella
      ovis (9/190: 4.7%), and Moraxella catarrhalis (6/190: 3.2%). Statistical analysis
      showed that alpacas harboring viridans streptococci and Moraxella species were
      significantly younger. Gender did not significantly affect type of bacterial
      isolation. There appeared to be no significant effect of age or gender on number
      of bacteria isolated. CONCLUSIONS: Gram-positive aerobes were most commonly
      cultured, with S. xylosus and viridans streptococci predominating. To the best of
      the authors' knowledge, this is the first report describing the presence of
      Moraxella species in the healthy conjunctival sac of alpacas. Alpacas harboring
      viridans streptococci and Moraxella species were significantly younger.

PMID- 25581470
TI  - Parent-child relational problem: field trial results, changes in DSM-5, and
      proposed changes for ICD-11.
AB  - Caregiving relationships are significant factors in the development, mediation,
      or moderation of childhood mental health problems. However, epidemiological and
      clinical research has been limited by lack of reliable, succinct, and
      standardized methods of assessing parent-child relationship constructs. The
      Relational Processes Workgroup (ad hoc to the DSM-5 process) proposed more
      specific criteria to define a parent-child relational problem (PCRP). These
      criteria were field tested in one of the DSM-5 Field trial sites, utilizing a
      similar research design as DSM-5. Participants included 133 symptomatic children
      (5-17 years) in active treatment for a mental health problem and their primary
      caregiver (86% mothers). Two separate clinicians, each blinded to the assessment
      of the other clinician as well as the DSM-5 diagnoses, interviewed the dyads
      within a 2-week period, utilizing the proposed PCRP criteria. Prior to each
      interview, parents were asked to write about their relationship with their child,
      and children (over the age of 10 years) filled out the Parental Bonding
      Instrument, Brief Current, and the Perceived Criticism Measure. Clinicians were
      able to read the narratives and see results of the child report measures before
      assessing the dyad. The weighted prevalence of a PCRP in this sample was 34%. The
      interclass kappa for overall agreement between clinicians was 0.58 (0.40, 0.72),
      which indicates good interrater reliability. Further, clinicians found the PCRP
      diagnostic criteria clinically useful and an improvement over the brief
      description of PCRP that was presented in DSM-IV. Relationships between children
      and their primary caregiver can be assessed in a reliable manner, based on
      clinical interview with the child-caregiver dyad and several self-report
      measures. 

PMID- 25581471
TI  - Late-stage C-H functionalization of complex alkaloids and drug molecules via
      intermolecular rhodium-carbenoid insertion.
AB  - Alkaloids constitute a large family of natural products possessing diverse
      biological properties. Their unique and complex structures have inspired numerous
      innovations in synthetic chemistry. In the realm of late-stage C-H
      functionalization, alkaloids remain a significant challenge due to the presence
      of the basic amine and a variety of other functional groups. Herein we report the
      first examples of dirhodium(II)-catalysed intermolecular C-H insertion into
      complex natural products containing nucleophilic tertiary amines to generate a C
      C bond. The application to a diverse range of alkaloids and drug molecules
      demonstrates remarkable chemoselectivity and predictable regioselectivity. The
      capacity for late-stage diversification is highlighted in the catalyst-controlled
      selective functionalizations of the alkaloid brucine. The remarkable selectivity
      observed, particularly for site-specific C-H insertion at N-methyl
      functionalities, offers utility in a range of applications where efficient
      installation of synthetic handles on complex alkaloids is desired. 

PMID- 25581472
TI  - Pain among institutionalized stroke patients and its relation to emotional
      distress and social engagement.
AB  - OBJECTIVE: Pain is a frequent long-term consequence of stroke, but its relation
      to emotional and social well-being is poorly studied in stroke populations. We
      aimed to identify the prevalence of substantial pain among institutionalized
      stroke patients and to explore its relation to emotional distress (ED) and low
      social engagement (SE). METHODS: In a cross-sectional design, we collected data
      of 274 chronic stroke patients in Dutch nursing homes. Observation lists were
      filled out in structured interviews with qualified nurse assistants who knew the
      residents well. Pain and SE were measured with the Resident Assessment Instrument
      for Long-term Care Facilities, and ED was measured with the Neuropsychiatric
      Inventory Questionnaire (NPIQ). RESULTS: Substantial pain was present in 28% of
      the residents, mostly located in the affected body side (68%). Multilevel
      regression analyses revealed that this pain was independently related to a 60%
      increase in NPIQ score (beta 3.18 [1.84-4.53]) and to clinically relevant
      symptoms of delusions (odds ratio [OR] 8.45 [1.82-39.05]), agitation/aggression
      (OR 3.82 [1.76-8.29]), depression (OR 3.49 [1.75-6.98]), and anxiety (OR 2.32
      [1.08-4.97]). Substantial pain was associated with low SE when adjusted for
      clinical covariates (OR 4.25 [1.72-10.53]), but only in residents with no/mild or
      severe cognitive impairment. This relation disappeared when additionally
      corrected for NPIQ score (OR 1.95 [0.71-5.39]). CONCLUSIONS: Pain is a serious
      and multidimensional problem among institutionalized stroke patients. It is
      related to increased ED, which in turn can be a pathway to low SE as an indicator
      of social vulnerability. Future research should reveal how pain management in
      nursing homes can be tailored to the needs of this patient group.

PMID- 25581473
TI  - Autonomy and empowerment in advanced practice registered nurses: lessons from New
      Mexico.
AB  - PURPOSE: The purpose of this study was to determine the association between
      autonomy and empowerment of advanced practice registered nurses (APRNs) and
      predictor variables of physician oversight, geographical location, and practice
      setting. As the Patient Protection and Affordable Care Act (PPACA) is
      implemented, these characteristics are vital to understanding how APRNs practice
      and the relationship of APRNs to other healthcare team members, including
      physicians. DATA SOURCES: This was a descriptive, correlational survey of APRNs
      in New Mexico exploring autonomy and empowerment in relation to variables of
      physician oversight, geographical location, and practice setting. CONCLUSIONS:
      New Mexico's APRN Nurse Practice Act supports independent practice and
      prescriptive authority. Results indicated that APRNs are highly empowered and
      autonomous. However, nearly 40% of respondents identified practicing with
      physician oversight. Further investigation of subscales of empowerment also
      provided insight of relationships among healthcare team members, particularly
      physicians. IMPLICATIONS FOR PRACTICE: This research provides additional
      knowledge for policy changes that support APRNs assuming more responsibility for
      primary care. However, understanding the APRN role within the healthcare team is
      necessary for effective implementation of primary care in New Mexico.

PMID- 25581474
TI  - Left main stem coronary stenosis associated with Cabrol grafting.

PMID- 25581475
TI  - Extreme carbon dioxide sorption hysteresis in open-channel rigid metal-organic
      frameworks.
AB  - A systematic study is presented of three closely related microporous metal
      organic frameworks the pore dimensions of which vary according to the choice of
      4,4'-bipyridyl linker. The tunable linker allows exploration of the effect of
      increasing pore dimensions on the sorption behavior of the frameworks. The MOFs
      described capture CO2 under supercritical conditions and continue to sequester
      the gas under ambient conditions. Gas sorption isotherms for CO2 are compared
      with thermogravimetric data, and the CO2 molecules in the channels of the
      frameworks could be modeled using single-crystal X-ray diffraction analysis.
      Crystallographic data were used to construct a theoretical model based on DFT
      methods to calculate framework electrostatic potential maps with a view to
      understanding the nature of the sorbate-sorbent interactions. 

PMID- 25581476
TI  - Presentation on US hospital websites of risks and benefits of transcatheter
      aortic valve replacement procedures.

PMID- 25581478
TI  - Poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c
      FA): a bioactive copolymer for specific targeting to folate receptor-positive
      cancer cells.
AB  - In this study, we present the preparation, characterization and application of a
      novel bioactive copolymer poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2
      oxazoline) (PLL-g-PMOXA-c-FA), which has a specific interaction with folate
      receptor (FR)-positive cancer cells. Glass surface immobilized with PLL-g-PMOXA-c
      FA was demonstrated to be adhesive to FR-positive cancer cells (HeLa, JEG-3)
      while nonadhesive to FR-negative ones (MCF-7, HepG2) in 3 h. The specific
      interaction between conjugated FA on the substrate and FRs on the cells could
      hardly be inhibited unless a high concentration (5 mM) of free FA was used due to
      the multivalent nature of it. The FA functionality ratio of the copolymer on the
      substrate had a significant influence on the adhesion of HeLa cells, and our
      experiments revealed that the affinity of the substrate to the cells declined
      dramatically with the decrease of functionality ratio. This was believed to be
      caused by the polydispersity of PMOXA tethers, as supported by GPC and ToF-SIMS
      data. As a proof of concept in the application of our material, we demonstrated
      successful recovery of HeLa cells from mixture with MCF-7 (1:100) on the
      copolymer-coated glass, and our results showed that both high sensitivity (95.6
      +/- 13.3%) and specificity (24.3 +/- 8.6%) were achieved. 

PMID- 25581479
TI  - The role of brain-derived neurotrophic factor in bone marrow stromal cell
      mediated spinal cord repair.
AB  - The ability of intraspinal bone marrow stromal cell (BMSC) transplants to elicit
      repair is thought to result from paracrine effects by secreted trophic factors
      including brain-derived neurotrophic factor (BDNF). Here we used gene therapy to
      increase or silence BDNF production in BMSCs to investigate the role of BDNF in
      BMSC-mediated neuroprotection. In a spinal cord organotypic culture, BMSC
      conditioned medium significantly enhanced spinal motoneuron survival by 64%
      compared with culture medium only. Only conditioned medium of BDNF-hypersecreting
      BMSCs sustained this neuroprotective effect. In a rat model of spinal cord
      contusion, a BDNF-dependent neuroprotective effect was confirmed; only with a
      subacute transplant of BDNF-hypersecreting BMSCs were significantly more spared
      motoneurons found at 4 weeks postinjury compared with vehicle controls. Spared
      nervous tissue volume was improved by 68% with both control BMSCs and BDNF
      hypersecreting BMSCs. In addition, blood vessel density in the contusion with
      BDNF-hypersecreting BMSCs was 35% higher compared with BMSC controls and sixfold
      higher compared with vehicle controls. BDNF-silenced BMSCs did not survive the
      first week of transplantation, and no neuroprotective effect was found at 4 weeks
      after transplantation. Together, our data broaden our understanding of the role
      of BDNF in BMSC-mediated neuroprotection and successfully exploit BDNF dependency
      to enhance anatomical spinal cord repair. 

PMID- 25581477
TI  - The what, where, and why of priority maps and their interactions with visual
      working memory.
AB  - Priority maps are winner-take-all neural mechanisms thought to guide the
      allocation of covert and overt attention. Here, we go beyond this standard
      definition and argue that priority maps play a much broader role in controlling
      goal-directed behavior. We start by defining what priority maps are and where
      they might be found in the brain; we then ask why they exist-the function that
      they serve. We propose that this function is to communicate a goal state to the
      different effector systems, thereby guiding behavior. Within this framework, we
      speculate on how priority maps interact with visual working memory and introduce
      our common source hypothesis, the suggestion that this goal state is maintained
      in visual working memory and used to construct all of the priority maps
      controlling the various motor systems. Finally, we look ahead and suggest
      questions about priority maps that should be asked next. 

PMID- 25581480
TI  - The new Editor-in-Chief of the Journal of Neuroimaging: Rohit Bakshi.

PMID- 25581482
TI  - Microbial biogeography of drinking water: patterns in phylogenetic diversity
      across space and time.
AB  - In this study, we collected water from different locations in 32 drinking water
      distribution networks in the Netherlands and analysed the spatial and temporal
      variation in microbial community composition by high-throughput sequencing of 16S
      rRNA gene amplicons. We observed that microbial community compositions of raw
      source and processed water were very different for each distribution network
      sampled. In each network, major differences in community compositions were
      observed between raw and processed water, although community structures of
      processed water did not differ substantially from end-point tap water. End-point
      water samples within the same distribution network revealed very similar
      community structures. Network-specific communities were shown to be surprisingly
      stable in time. Biofilm communities sampled from domestic water metres varied
      distinctly between households and showed no resemblance to planktonic communities
      within the same distribution networks. Our findings demonstrate that high
      throughput sequencing provides a powerful and sensitive tool to probe microbial
      community composition in drinking water distribution systems. Furthermore, this
      approach can be used to quantitatively compare the microbial communities to match
      end-point water samples to specific distribution networks. Insight in the ecology
      of drinking water distribution systems will facilitate the development of
      effective control strategies that will ensure safe and high-quality drinking
      water. 

PMID- 25581483
TI  - Advanced bronchogenic carcinoma presented as cardiac tamponade: a case report and
      a review of the literature.
AB  - Although most fatal lung tumors are well diagnosed before a patient's death,
      occasionally forensic pathologists encounter cases of sudden death in which the
      presence of a primary small cell lung carcinoma was not suspected. We present the
      case of a 49-year-old man asymptomatic until 2 days before his death. The autopsy
      revealed a huge tumorous mass originating from the central bronchus, infiltrating
      the large vessels, pulmonary parenchyma, pericardium, and the right ventricle of
      the heart. Pericardial sac was distended due to pericardial effusion (700 mL).
      Examination also revealed metastases to the liver, pancreas, and right adrenal
      gland. Microscopic examination identified the primary neoplasm as a small cell
      lung carcinoma after common stain of hematoxylin-eosin, and additional
      immunohistochemistry were performed. 

PMID- 25581484
TI  - Strategic categorization of available research relating to sexual assault and
      rape facilitates more accurate interpretation of injury data.
AB  - The available research evidence pertaining to anogenital injury in victims of
      sexual violence presents a very wide range of injury prevalence data. As such, it
      is extraordinarily challenging for health care practitioners involved in clinical
      forensic examination of victims of sexual violence to place their examination
      findings in to context. It is generally accepted that the broad range of existing
      injury prevalence data is reflective of heterogeneous research study
      methodologies and clinical practice techniques. Thus, health care practitioners
      should be encouraged to present their evidence in the context of the prevalence
      data that are most representative of their clinical practice. Presented herein is
      a simple categorization of existing prevalence data in accordance with national
      clinical practice guidelines. The range of anogenital injury prevalence is
      narrower when presented in this manner than when taken as a whole. This will
      facilitate health care practitioners in presenting their examination findings in
      the context of research literature that is most representative of their clinical
      practice. 

PMID- 25581485
TI  - Associations between the number of natural teeth and metabolic syndrome in
      adults.
AB  - AIM: To explore associations between the number of natural teeth and metabolic
      syndrome in adults. MATERIAL AND METHODS: Cross-sectional data from the National
      Health and Nutrition Examination Survey 2005-2008 were used. Eligible adults (n =
      5511) were classified into four groups by their number of natural teeth
      (excluding third molars): full dentition, 21-27 teeth, 1-20 teeth, or edentulous.
      Metabolic syndrome was defined by diagnostic guidelines from the American Heart
      Association and National Heart, Lung, and Blood Institute. Associations were
      analysed by survey logistic regression. Biometric and metabolic parameters in
      different dentition groups were compared. RESULTS: Adjusting for age, gender,
      race/ethnicity, ratio of family income to poverty, physical activity, smoking,
      and energy intake, tooth loss was significantly associated with metabolic
      syndrome (p = 0.002). Compared to participants with full dentition, the odds were
      32% higher in those with 21-27 teeth, 55% higher in those with 1-20 teeth and 79%
      higher in edentulous participants. The number of natural teeth was inversely
      associated with body mass index, waist circumference, blood pressure, fasting
      plasma glucose and insulin concentrations (p < 0.01 for all); it was positively
      associated with serum HDL cholesterol concentration (p = 0.003). CONCLUSIONS: The
      number of natural teeth is inversely associated with the presence of metabolic
      syndrome in adults.

PMID- 25581486
TI  - Mechanistic studies on the autoxidation of alpha-guaiene: structural diversity of
      the sesquiterpenoid downstream products.
AB  - Two unstable hydroperoxides, 6b and 10a, and 13 downstream sesquiterpenoids have
      been isolated from the autoxidation mixture of the bicyclic sesquiterpene alpha
      guaiene (1) on cellulose filter paper. One of the significant natural products
      isolated was rotundone (2), which is the only known impact odorant displaying a
      peppery aroma. Other products included corymbolone (4a) and its C-6 epimer 4b,
      the (2R)- and (2S)-rotundols (7a/b), and several hitherto unknown epimers of
      natural chabrolidione A, namely, 7-epi-chabrolidione A (3a) and 1,7-epi
      chabrolidione A (3b). Two 4-hydroxyrotundones (8a/b) and a range of epoxides
      (9a/b and 5a/b) were also formed in significant amounts after autoxidation. Their
      structures were elucidated on the basis of spectroscopic data and X-ray
      crystallography, and a number of them were confirmed through total synthesis. The
      mechanisms of formation of the majority of the products may be accounted for by
      initial formation of the 2- and 4-hydroperoxyguaienes (6a/b and 10a/b) followed
      by various fragmentation or degradation pathways. Given that alpha-guaiene (1) is
      well known to exist in the essential oils of numerous plants, coupled with the
      fact that aerial oxidation to form this myriad of downstream oxidation products
      occurs readily at ambient temperature, suggests that many of them have been
      overlooked during previous isolation studies from natural sources. 

PMID- 25581488
TI  - Covalent organic frameworks formed with two types of covalent bonds based on
      orthogonal reactions.
AB  - Covalent organic frameworks (COFs) are excellent candidates for various
      applications. So far, successful methods for the constructions of COFs have been
      limited to a few condensation reactions based on only one type of covalent bond
      formation. Thus, the exploration of a new judicious synthetic strategy is a
      crucial and emergent task for the development of this promising class of porous
      materials. Here, we report a new orthogonal reaction strategy to construct COFs
      by reversible formations of two types of covalent bonds. The obtained COFs
      consisting of multiple components show high surface area and high H2 adsorption
      capacity. The strategy is a general protocol applicable to construct not only
      binary COFs but also more complicated systems in which employing regular
      synthetic methods did not work. 

PMID- 25581487
TI  - Elevated AST-to-platelet ratio index is associated with increased all-cause
      mortality among HIV-infected adults in Zambia.
AB  - BACKGROUND & AIMS: We investigated the association between significant liver
      fibrosis, determined by AST-to-platelet ratio index (APRI), and all-cause
      mortality among HIV-infected patients prescribed antiretroviral therapy (ART) in
      Zambia. METHODS: Among HIV-infected adults who initiated ART, we categorized
      baseline APRI scores according to established thresholds for significant hepatic
      fibrosis (APRI >=1.5) and cirrhosis (APRI >=2.0). Using multivariable logistic
      regression we identified risk factors for elevated APRI including demographic
      characteristics, body mass index (BMI), HIV clinical and immunological status,
      and tuberculosis. In the subset tested for hepatitis B surface antigen (HBsAg),
      we investigated the association of hepatitis B virus co-infection with APRI
      score. Using Kaplan-Meier analysis and Cox proportional hazards regression we
      determined the association of elevated APRI with death during ART. RESULTS: Among
      20 308 adults in the analysis cohort, 1027 (5.1%) had significant liver fibrosis
      at ART initiation including 616 (3.0%) with cirrhosis. Risk factors for
      significant fibrosis or cirrhosis included male sex, BMI <18, WHO clinical stage
      3 or 4, CD4(+) count <200 cells/mm(3) , and tuberculosis. Among the 237 (1.2%)
      who were tested, HBsAg-positive patients had four times the odds (adjusted odds
      ratio, 4.15; 95% CI, 1.71-10.04) of significant fibrosis compared HBsAg
      negatives. Both significant fibrosis (adjusted hazard ratio 1.41, 95% CI, 1.21
      1.64) and cirrhosis (adjusted hazard ratio 1.57, 95% CI, 1.31-1.89) were
      associated with increased all-cause mortality. CONCLUSION: Liver fibrosis may be
      a risk factor for mortality during ART among HIV-infected individuals in Africa.
      APRI is an inexpensive and potentially useful test for liver fibrosis in resource
      constrained settings.

PMID- 25581489
TI  - Palladium(II)-catalyzed highly enantioselective C-H arylation of
      cyclopropylmethylamines.
AB  - C-H arylation via a Pd(II)/Pd(IV) catalytic cycle has been one of the most
      extensively studied C-H activation reactions since the 1990s. Despite the rapid
      development of this reaction in the past two decades, an enantioselective version
      has not been reported to date. Herein, we report a Pd(II)-catalyzed highly
      enantioselective (up to 99.5% ee) arylation of cyclopropyl C-H bonds with aryl
      iodides using mono-N-protected amino acid (MPAA) ligands, providing a new route
      for the preparation of chiral cis-aryl-cyclopropylmethylamines. The
      enantiocontrol is also shown to override the diastereoselectivity of chiral
      substrates. 

PMID- 25581490
TI  - Use of alprazolam to facilitate mare-foal bonding in an aggressive postparturient
      mare.

PMID- 25581492
TI  - Branching of lung epithelium in vitro occurs in the absence of endothelial cells.
AB  - BACKGROUND: Early lung morphogenesis is driven by tissue interactions. Signals
      from the lung mesenchyme drive epithelial morphogenesis, but which individual
      mesenchymal cell types are influencing early epithelial branching and
      differentiation remains unclear. It has been shown that endothelial cells are
      involved in epithelial repair and regeneration in the adult lung, and they may
      also play a role in driving early lung epithelial branching. These data, in
      combination with evidence that endothelial cells influence early morphogenetic
      events in the liver and pancreas, led us to hypothesize that endothelial cells
      are necessary for early lung epithelial branching. RESULTS: We blocked vascular
      endothelial growth factor (VEGF) signaling in embryonic day (E) 12.5 lung
      explants with three different VEGF receptor inhibitors (SU5416, Ki8751, and
      KRN633) and found that in all cases the epithelium was able to branch despite the
      loss of endothelial cells. Furthermore, we found that distal lung mesenchyme
      depleted of endothelial cells retained its ability to induce terminal branching
      when recombined with isolated distal lung epithelium (LgE). Additionally,
      isolated E12.5 primary mouse lung endothelial cells, or human lung microvascular
      endothelial cells (HMVEC-L), were not able to induce branching when recombined
      with LgE. CONCLUSIONS: Our observations support the conclusion that endothelial
      cells are not required for early lung branching.

PMID- 25581493
TI  - Computational fluid dynamic modelling of the effect of ventilation mode and
      tracheal tube position on air flow in the large airways.
AB  - We have used computational fluid dynamic modelling to study the effects of
      tracheal tube size and position on regional gas flow in the large airways. Using
      a three-dimensional mathematical model, we simulated flow with and without a
      tracheal tube, replicating both physiological and artificial breathing.
      Ventilation through a tracheal tube increased proportional flow to the left lung
      from 39.5% with no tube to 43.1-47.2%, depending on tube position. Ventilation
      mode and tube distance from the carina had no effect on flow. Lateral
      displacement and deflection of the tube increased ventilation to the ipsilateral
      lung; for example, when deflected 10 degrees  to the left of centre, flow to the
      left lung increased from 43.8 to 53.7%. Because of the small diameter of a
      tracheal tube relative to the trachea, gas exits a tube at high velocity such
      that regional ventilation may be affected by changes in the position and angle of
      the tube. 

PMID- 25581491
TI  - Time-frequency theta and delta measures index separable components of feedback
      processing in a gambling task.
AB  - Previous work using gambling tasks indicate that the feedback negativity (FN)
      reflects primary or salient stimulus attributes (often gain vs. loss), whereas
      the feedback-P300 appears sensitive to secondary stimulus information. A recent
      time-frequency approach has characterized separable theta (3-7 Hz) and delta (0-3
      Hz) feedback processes, independently sensitive to primary feedback attributes,
      specifically loss and gain outcomes, respectively. The current study extends this
      time-frequency work to evaluate both primary and secondary (relative outcome and
      outcome magnitude) feedback attributes. Consistent with previous reports, theta
      indexed an initial, lower-level response sensitive to the primary (most salient)
      feedback attributes (specifically losses), while delta was sensitive to both
      primary attributes (specifically gains) and assessed secondary stimulus features.

PMID- 25581494
TI  - Multiple mitral valve aneurysms.

PMID- 25581496
TI  - Magnetic mixed hemimicelles solid-phase extraction coupled with high-performance
      liquid chromatography for the extraction and rapid determination of six
      fluoroquinolones in environmental water samples.
AB  - In this study, a mixed hemimicelle solid-phase extraction method based on Fe3 O4
      nanoparticles coated with sodium dodecyl sulfate was applied for the
      preconcentration and fast isolation of six fluoroquinolones in environmental
      water samples before high-performance liquid chromatography determination. The
      main factors affecting the extraction efficiency of the analytes, such as amount
      of surfactant, amount of Fe3 O4 nanoparticles, extraction time, sample volume,
      sample pH, ionic strength, and desorption conditions, were investigated and
      optimized. The method has detection limits from 0.05 to 0.1 ng/mL and good
      linearity (r >= 09948) in the range 0.1-200 ng/mL depending on the
      fluoroquinolone. The enrichment factor is ~200. The recoveries (at spiked levels
      of 1, 5, and 50 ng/mL) are in the range of 79-120%. 

PMID- 25581497
TI  - Response to editorial comment to Manually controlled targeted prostate biopsy
      with real-time fusion imaging of multiparametric magnetic resonance imaging and
      transrectal ultrasound: an early experience.

PMID- 25581495
TI  - Optical coherence tomography guided microinjections in live mouse embryos: high
      resolution targeted manipulation for mouse embryonic research.
AB  - The ability to conduct highly localized delivery of contrast agents, viral
      vectors, therapeutic or pharmacological agents, and signaling molecules or dyes
      to live mammalian embryos is greatly desired to enable a variety of studies in
      the field of developmental biology, such as investigating the molecular
      regulation of cardiovascular morphogenesis. To meet such a demand, we introduce,
      for the first time, the concept of employing optical coherence tomography (OCT)
      guide microinjections in live mouse embryos, which provides precisely targeted
      manipulation with spatial resolution at the micrometer scale. The feasibility
      demonstration is performed with experimental studies on cultured live mouse
      embryos at E8.5 and E9.5. Additionally, we investigate the OCT-guided
      microinjection of gold-silica nanoshells to the yolk sac vasculature of live
      cultured mouse embryos at the stage when the heart just starts to beat, as a
      potential approach for dynamic assessment of cardiovascular form and function
      before the onset of blood cell circulation. Also, the capability of OCT to
      quantitatively monitor and measure injection volume is presented. Our results
      indicate that OCT-guided microinjection could be a useful tool for mouse
      embryonic research.

PMID- 25581498
TI  - The impact of humanitarian context conditions and individual characteristics on
      aid worker retention.
AB  - High employee turnover rates constitute a major challenge to effective aid
      provision. This study examines how features of humanitarian work and aid workers'
      individual characteristics affect retention within one humanitarian organisation,
      Medecins Sans Frontieres (MSF) Holland. The study extends existing research by
      providing new theoretical explanations of employment opportunities and
      constraints and by engaging in the first large-scale quantitative analysis of aid
      worker retention. Using a database of field staff (N=1,955), a logistic
      regression is performed of the likelihood of reenlistment after a first mission.
      The findings demonstrate that only 40 per cent of employees reenlist for a second
      mission with MSF Holland, and that workplace location and security situation,
      age, and gender have no significant effect. Individuals are less likely to
      reenlist if they returned early from the first mission for a personal reason, are
      in a relationship, are medical doctors, or if they come from highly developed
      countries. The paper reflects on the findings in the light of policy. 

PMID- 25581499
TI  - Dissolved organic carbon quality and sorption of organic pollutants in the Baltic
      Sea in light of future climate change.
AB  - Regional climate change scenarios predict increased temperature and precipitation
      in the northern Baltic Sea, leading to a greater runoff of fresh water and
      terrestrial dissolved organic carbon (DOC) within the second part of the 21st
      century. As a result, the current north to south gradient in temperature and
      salinity is likely to be shifted further toward the south. To examine if such
      climate change effects would cause alterations in the environmental fate of
      organic pollutants, spatial variations of DOC quality and sorption behavior
      toward organic contaminants were examined using multiple analytical methods. The
      results showed declining contents of aromatic functional groups in DOC along a
      north to south gradient. Similarly, the sorption of a diverse set of organic
      contaminants to DOC also showed spatial differences. The sorption behavior of
      these contaminants was modeled using poly parameter linear energy relationships.
      The resulting molecular descriptors indicated clear differences in the sorption
      properties of DOC sampled in northern and southern parts of the Baltic Sea, which
      imply that more organic contaminants are sorbed to DOC in the northern part. The
      extent of this sorption process determines whether individual contaminants will
      partition to biota via direct uptake or through sorption to DOC, which serves as
      food source for bacteria-based food-webs. 

PMID- 25581500
TI  - Approaching the downsizing limit of silicon for surface-controlled lithium
      storage.
AB  - Graphene-sheet-supported uniform ultrasmall (~3 nm) silicon quantum dots have
      been successfully synthesized by a simple and effective self-assembly strategy,
      exhibiting unprecedented fast, surface-controlled lithium-storage behavior and
      outstanding lithium-storage properties including extraordinary rate capability
      and remarkable cycling stability, attributable to the intrinsic role of
      approaching the downsizing limit of silicon. 

PMID- 25581501
TI  - Across the board: Hiroshi Imahori.
AB  - In this series of articles the board members of ChemSusChem discuss recent
      research articles that they consider of exceptional quality and importance for
      sustainability. This entry features Prof. Hiroshi Imahori, who discusses a
      concept in which photosensitizers and binuclear catalysts, both based on
      ruthenium complexes, can be combined to efficiently oxidize water similar to the
      Photosystem II in plants. 

PMID- 25581504
TI  - Control of charge transport in the perovskite CH3 NH3 PbI3 thin film.
AB  - Carrier density and transport properties in the CH3 NH3 PbI3 thin film have been
      investigated. It is found that the carrier density, the depletion field, and the
      charge collection and transport properties in the CH3 NH3 PbI3 absorber film can
      be controlled effectively by different concentrations of reactants. That is, the
      carrier properties and the self-doping characteristics in CH3 NH3 PbI3 films are
      strongly influenced by the reaction thermodynamic and kinetic processes.
      Furthermore, by employing mixed solvents with ethanol and isopropanol to deposit
      the CH3 NH3 PbI3 film, the charge collection and transport efficiencies are
      improved significantly, thereby yielding an overall enhanced cell performance. 

PMID- 25581502
TI  - Kruppel-like factor KLF4 facilitates cutaneous wound healing by promoting
      fibrocyte generation from myeloid-derived suppressor cells.
AB  - Pressure ulcers (PUs) are serious skin injuries whereby the wound healing process
      is frequently stalled in the inflammatory phase. Myeloid-derived suppressor cells
      (MDSCs) accumulate as a result of inflammation and promote cutaneous wound
      healing by mechanisms that are not fully understood. Recently, MDSCs have been
      shown to differentiate into fibrocytes, which serve as emerging effector cells
      that enhance cell proliferation in wound healing. We postulate that in wound
      healing MDSCs not only execute their immunosuppressive function to regulate
      inflammation but also stimulate cell proliferation once they differentiate into
      fibrocytes. In the current study, by using full-thickness and PU mouse models, we
      found that Kruppel-like factor 4 (KLF4) deficiency resulted in decreased
      accumulation of MDSCs and fibrocytes, and wound healing was significantly
      delayed. Conversely, KLF4 activation by the plant-derived product Mexicanin I
      increased the number of MDSCs and fibrocytes and accelerated the wound healing.
      Collectively, our study revealed a previously unreported function of MDSCs in
      cutaneous wound healing and identified Mexicanin I as a potential agent to
      accelerate PU wound healing. 

PMID- 25581503
TI  - The large conductance calcium-activated potassium channel affects extrinsic and
      intrinsic mechanisms of apoptosis.
AB  - The large-conductance calcium-activated K(+) or BK channel underlies electrical
      signals in a number of different cell types. Studies show that BK activity can
      also serve to regulate cellular homeostasis by protecting cells from apoptosis
      resulting from events such as ischemia. Recent coimmunoprecipitation studies,
      combined with mass spectrometry, suggest putative protein partners that interact
      with BK to regulate intrinsic and extrinsic apoptotic pathways. This study tests
      two of those partners to determine the effects on these two signaling pathways.
      Through reciprocal coimmunoprecipitation (coIP) experiments, we show that BK
      interacts with p53 and fas-associated protein with death domain (FADD) in mouse
      brain and when overexpressed in a heterologous expression system, such as HEK293
      cells. Moreover, coIP experiments with N- and C-terminal fragments reveal that
      FADD interacts with the C-terminus of BK, whereas p53 interacts with either the N
      or the C-terminus. Immunolocalization studies show that BK colocalizes with p53
      and FADD in the mitochondrion and plasmalemma, respectively. HEK cells that
      stably express BK are more resistant to apoptosis when p53 or FADD is
      overexpressed or when their intrinsic and extrinsic pathways are stimulated via
      mitomycin C or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL),
      respectively. Moreover, when stimulating with TRAIL, caspase-8 activation
      decreases in BK-expressing cells. These data suggest that BK is part of a larger
      complex of proteins that protects against apoptosis by interacting with
      proapoptotic proteins, such as p53 and FADD.

PMID- 25581505
TI  - Continued participation in a ten-year tight control treat-to-target study in
      rheumatoid arthritis: why keep patients doing their best?
AB  - OBJECTIVE: To identify risk factors for early study termination and motivators
      for adherence to a long-term followup trial and to improve completeness of long
      term studies. METHODS: Risk factors for early termination in 508 included
      patients were identified through Cox regression analysis. Patients completing the
      10-year followup filled in a questionnaire on possible motives for continued
      study participation. RESULTS: Risk factors for early termination were higher age
      (hazard ratio [HR] 1.03, 95% confidence interval [95% CI] 1.02-1.04), functional
      disability during the preceding year (HR 1.54, 95% CI 1.20-1.99), having achieved
      drug-free remission (HR 6.62, 95% CI 2.07-21.14), limited joint damage (HR 0.98,
      95% CI 0.97-0.995 for actual damage; HR 0.83, 95% CI 0.73-0.94 for damage
      progression), and few adverse events (HR 0.35, 95% CI 0.26-0.47). A total of 288
      of 313 patients (92%) attending the last visit answered the questionnaire. The
      majority mentioned contributing to scientific research (97% agreed), helping
      other patients (91%), and learning about new treatment strategies (84%) and their
      disease (85%) as reasons to continue participation. Next, patients mentioned
      tight control (202 of 278 patients), good treatment strategy (128 of 278), good
      medication (117 of 278), and good half-term results (102 of 278) as motivators.
      More than 95% of patients experienced participation "as expected" or "better than
      expected." Additional examinations during yearly visits (extra questionnaires,
      imaging) were mentioned as "worse than expected" (10%), as was answering routine
      questionnaires (7%). CONCLUSION: Continued participation was relatively high in
      the Treatment Strategies for Rheumatoid Arthritis (BeSt) Study. Higher age,
      functional disability, drug-free remission, little joint damage, and few adverse
      events predicted early study termination. Main motives for continued
      participation were a willingness to contribute to research, help future patients,
      and because patients had good experiences with the study protocol.

PMID- 25581506
TI  - Overweight, central obesity, and cardiometabolic risk factors in pediatric liver
      transplantation.
AB  - PTMS describes the presence of >=3 cardiometabolic risk factors that include
      obesity, hypertension, dyslipidemia, and IR. The prevalence of the clustering of
      >=3 cardiometabolic risk factors or central obesity has not been studied in
      pediatric LT recipients. Single-center, cross-sectional study. INCLUSION
      CRITERIA: LT recipients 2-18 yr-old, at least one yr post-LT. EXCLUSION CRITERIA:
      recipients of liver retransplants or multivisceral transplants. Eighty-seven
      patients were identified. Median age was 9.8 yr (range 2-18), median time since
      LT was 6.9 yr (range 1-17). The most common indication for LT was biliary atresia
      (56%), and the most frequently used immunosuppressant was tacrolimus (80%). The
      prevalence of overweight and obesity was 21% and 5%, respectively. Central
      obesity affected 14%, hypertension 44%, IR 27%, low HDL 20%, and
      hypertriglyceridemia 39% of patients. The prevalence of >=3 cardiometabolic risk
      factors was 19%. Fifty percent of the overweight/obese patients had >=3 risk
      factors. Time since transplant, immunosuppression and renal function were not
      different between those with <3 or >=3 risk factors. Clustering of
      cardiometabolic risk factors is prevalent in pediatric LT recipients, suggesting
      an increased risk of future CV events.

PMID- 25581507
TI  - Vestibular rehabilitation for unilateral peripheral vestibular dysfunction.
AB  - BACKGROUND: This is an update of a Cochrane review first published in The
      Cochrane Library in Issue 4, 2007 and previously updated in 2011.Unilateral
      peripheral vestibular dysfunction (UPVD) can occur as a result of disease, trauma
      or postoperatively. The dysfunction is characterised by complaints of dizziness,
      visual or gaze disturbances and balance impairment. Current management includes
      medication, physical manoeuvres and exercise regimes, the latter known
      collectively as vestibular rehabilitation. OBJECTIVES: To assess the
      effectiveness of vestibular rehabilitation in the adult, community-dwelling
      population of people with symptomatic unilateral peripheral vestibular
      dysfunction. SEARCH METHODS: We searched the Cochrane Ear, Nose and Throat
      Disorders Group Trials Register; the Cochrane Central Register of Controlled
      Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews;
      Cambridge Scientific Abstracts; ISRCTN and additional sources for published and
      unpublished trials. The most recent search was 18 January 2014. SELECTION
      CRITERIA: Randomised controlled trials of adults living in the community,
      diagnosed with symptomatic unilateral peripheral vestibular dysfunction. We
      sought comparisons of vestibular rehabilitation versus control (e.g. placebo),
      other treatment (non-vestibular rehabilitation, e.g. pharmacological) or another
      form of vestibular rehabilitation. Our primary outcome measure was change in the
      specified symptomatology (for example, proportion with dizziness resolved,
      frequency or severity of dizziness). Secondary outcomes were measures of
      function, quality of life and/or measure(s) of physiological status, where
      reproducibility has been confirmed and shown to be relevant or related to health
      status (for example, posturography), and adverse effects DATA COLLECTION AND
      ANALYSIS: We used the standard methodological procedures expected by The Cochrane
      Collaboration. MAIN RESULTS: We included 39 studies involving 2441 participants
      with unilateral peripheral vestibular disorders in the review. Trials addressed
      the effectiveness of vestibular rehabilitation against control/sham
      interventions, medical interventions or other forms of vestibular rehabilitation.
      Non-blinding of outcome assessors and selective reporting were threats that may
      have biased the results in 25% of studies, but otherwise there was a low risk of
      selection or attrition bias.Individual and pooled analyses of the primary
      outcome, frequency of dizziness, showed a statistically significant effect in
      favour of vestibular rehabilitation over control or no intervention (odds ratio
      (OR) 2.67, 95% confidence interval (CI) 1.85 to 3.86; four studies, 565
      participants). Secondary outcomes measures related to levels of activity or
      participation measured, for example, with the Dizziness Handicap Inventory, which
      also showed a strong trend towards significant differences between the groups
      (standardised mean difference (SMD) -0.83, 95% CI -1.02 to -0.64). The exception
      to this was when movement-based vestibular rehabilitation was compared to
      physical manoeuvres for benign paroxysmal positional vertigo (BPPV), where the
      latter was shown to be superior in cure rate in the short term (OR 0.19, 95% CI
      0.07 to 0.49). There were no reported adverse effects. AUTHORS' CONCLUSIONS:
      There is moderate to strong evidence that vestibular rehabilitation is a safe,
      effective management for unilateral peripheral vestibular dysfunction, based on a
      number of high-quality randomised controlled trials. There is moderate evidence
      that vestibular rehabilitation resolves symptoms and improves functioning in the
      medium term. However, there is evidence that for the specific diagnostic group of
      BPPV, physical (repositioning) manoeuvres are more effective in the short term
      than exercise-based vestibular rehabilitation; although a combination of the two
      is effective for longer-term functional recovery. There is insufficient evidence
      to discriminate between differing forms of vestibular rehabilitation.

PMID- 25581508
TI  - One-step synthesis of degradable T(1)-FeOOH functionalized hollow mesoporous
      silica nanocomposites from mesoporous silica spheres.
AB  - The combination of a hollow mesoporous structure and a magnetic resonance (MR)
      contrast agent has shown its potential in simultaneous drug delivery and cell
      tracking applications. However, the preparation of this kind of nanocomposite is
      complicated and usually takes several days, which is unsuitable for scaled-up
      production. To overcome these hurdles, we report herein a facile method to
      synthesize iron oxide hydroxide functionalized hollow mesoporous silica spheres
      (FeOOH/HMSS) in a one-step manner. By carefully controlling the reaction kinetics
      of K2FeO4 in water, the gram-scale production of FeOOH/HMSS can be readily
      achieved at 60  degrees C for as short as 30 min. Most importantly, this
      synthetic process is also cost-effective and eco-friendly in both the precursor
      (K2FeO4 and H2O) and the product (FeOOH). The mechanism for the formation of a
      hollow structure was carefully investigated, which involves the synergetic effect
      of the surfactant CTAB and the side product KOH. Having outstanding
      biocompatibility, these degradable nanocolloids also demonstrate their
      feasibility in in vitro/vivo MR imaging and in vitro drug delivery. 

PMID- 25581431
TI  - Identification of six new susceptibility loci for invasive epithelial ovarian
      cancer.
AB  - Genome-wide association studies (GWAS) have identified 12 epithelial ovarian
      cancer (EOC) susceptibility alleles. The pattern of association at these loci is
      consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC.
      After imputation to 1000 Genomes Project data, we assessed associations of 11
      million genetic variants with EOC risk from 15,437 cases unselected for family
      history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211
      BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results
      in a meta-analysis. This new study design yielded increased statistical power,
      leading to the discovery of six new EOC susceptibility loci. Variants at 1p36
      (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were
      associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were
      specifically associated with the serous EOC subtype, all with P < 5 * 10(-8).
      Incorporating these variants into risk assessment tools will improve clinical
      risk predictions for BRCA1 and BRCA2 mutation carriers. 

PMID- 25581510
TI  - Multi-center reproducibility of neurochemical profiles in the human brain at 7 T.
AB  - The purpose of this work was to harmonize data acquisition and post-processing of
      single voxel proton MRS ((1) H-MRS) at 7 T, and to determine metabolite
      concentrations and the accuracy and reproducibility of metabolite levels in the
      adult human brain. This study was performed in compliance with local
      institutional human ethics committees. The same seven subjects were each examined
      twice using four different 7 T MR systems from two different vendors using an
      identical semi-localization by adiabatic selective refocusing spectroscopy
      sequence. Neurochemical profiles were obtained from the posterior cingulate
      cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were
      analyzed with LCModel, and sources of variation in concentrations ('subject',
      'institute' and 'random') were identified with a variance component analysis.
      Concentrations of 10-11 metabolites, which were corrected for T1 , T2 ,
      magnetization transfer effects and partial volume effects, were obtained with
      mean Cramer-Rao lower bounds below 20%. Data variances and mean concentrations in
      GM and WM were comparable for all institutions. The primary source of variance
      for glutamate, myo-inositol, scyllo-inositol, total creatine and total choline
      was between subjects. Variance sources for all other metabolites were associated
      with within-subject and system noise, except for total N-acetylaspartate,
      glutamine and glutathione, which were related to differences in signal-to-noise
      ratio and in shimming performance between vendors. After multi-center
      harmonization of acquisition and post-processing protocols, metabolite
      concentrations and the sizes and sources of their variations were established for
      neurochemical profiles in the healthy brain at 7 T, which can be used as guidance
      in future studies quantifying metabolite and neurotransmitter concentrations with
      (1) H-MRS at ultra-high magnetic field.

PMID- 25581509
TI  - REM sleep and depressive symptoms in a population-based study of middle-aged and
      elderly persons.
AB  - Alterations in rapid eye movement sleep have been consistently related to
      depression in clinical studies. So far, there is limited evidence from population
      based studies for this association of rapid eye movement sleep alterations with
      depressive symptoms. In 489 participants of the Rotterdam Study, we assessed
      rapid eye movement sleep latency, rapid eye movement sleep duration and rapid eye
      movement density with ambulant polysomnography, and depressive symptoms with the
      Center of Epidemiologic Studies-Depression Scale. A longer rapid eye movement
      sleep latency (B = 0.002, P = 0.025) and higher rapid eye movement density (B =
      0.015, P = 0.046) were related to depressive symptoms after age-sex adjustment.
      When we excluded persons who used sleep medication or medication for the nervous
      system (n = 124), only rapid eye movement density remained related to depressive
      symptoms (B = 0.018, P = 0.027). Our results suggest that rapid eye movement
      density is a marker of depressive symptoms in the general population, and that
      associations of rapid eye movement sleep with depressive symptoms are modified by
      the use of medication.

PMID- 25581512
TI  - The predictors of survival in Chinese amyotrophic lateral sclerosis patients.
AB  - Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative
      disease, so it is important to explore the survival factors for ALS. Our aim was
      to evaluate the predictors of survival in Chinese ALS patients. A total of 1049
      sporadic ALS patients were enrolled. Kaplan-Meier curves were used to compare
      survival time. Cox proportional hazards function and the hazard ratio were used
      to identify adjusted prognostic predictors. Results showed that the mean age of
      onset was 52.6 +/- 12.0 years. During follow-up, 155 patients (14.8%) were lost
      and 378 patients were deceased. Median survival was 33 months for the deceased
      patients. In the adjusted Cox proportional hazard model, age of onset, diagnosis
      delay, rate of disease progression, and non-invasive positive pressure
      ventilation (NIPPV) treatment had an effect on survival in ALS. In conclusion,
      our study provides information on survival factors for Chinese ALS patients.
      Although the onset age of Chinese ALS patients is earlier than that of Caucasian
      patients, survival factors, including the age of onset, diagnostic delay, rate of
      disease progression, and NIPPV treatment, are similar. 

PMID- 25581513
TI  - Possible rare congenital dysinnervation disorder: congenital ptosis associated
      with adduction.
AB  - Ptosis is defined as an abnormally low position of the upper eyelid margin. It
      can be congenital or acquired, uni or bilateral, and isolated or associated with
      other ocular and nonocular defects. We report a case of a female child, aged 8
      years, with congenital right ptosis increased on right adduction and with left
      ptosis on left adduction. There was no horizontal ocular movement limitation.
      Apparent underaction of the right inferior oblique muscle was also present. We
      believe that within the possible mechanisms it is more likely that it is a
      congenital innervation dysgenesis syndrome (CID)/congenital cranial
      dysinnervation disorder (CCDD). 

PMID- 25581511
TI  - The Synthesis and Evaluation of C7-Substituted alpha-Tetralone Derivatives as
      Inhibitors of Monoamine Oxidase.
AB  - Based on a previous report that alpha-tetralone (3,4-dihydro-2H-naphthalen-1-one)
      is a promising scaffold for the design of highly potent inhibitors of the enzyme,
      monoamine oxidase, the present study investigates the monoamine oxidase
      inhibitory properties of a synthetic series of fifteen C7-substituted alpha
      tetralone derivatives. Arylalkyloxy substitution on C7 of the alpha-tetralone
      moiety yielded compounds with high inhibition potencies toward the human
      monoamine oxidase-B isoform with all compounds possessing IC50 values in the
      submicromolar range (0.00089-0.047 MUm). The C7-substituted alpha-tetralones also
      were highly potent monoamine oxidase-A inhibitors with thirteen (of fifteen)
      compounds possessing IC50 values in the submicromolar range (0.010-0.741 MUm).
      The alpha-tetralones were, however, in each instance selective for monoamine
      oxidase-B over the monoamine oxidase-A isoform. Dialyses of enzyme-inhibitor
      mixtures show that, while a representative inhibitor acts as a reversible
      monoamine oxidase-A inhibitor, inhibition of monoamine oxidase-B is not readily
      reversed by dialysis. Using a molecular modeling approach, possible binding
      orientations and interactions of selected alpha-tetralones with the active sites
      of the monoamine oxidases are also proposed. This study suggests that C7
      substituted alpha-tetralones are promising monoamine oxidase inhibitors and may
      represent lead compounds for the development of therapies for Parkinson's disease
      and depression. 

PMID- 25581515
TI  - Survival outcome of patients with nasopharyngeal carcinoma: a nationwide analysis
      of 13 407 patients in Taiwan.
AB  - OBJECTIVES: We reported the contemporary survival outcome of patients with
      nasopharyngeal carcinoma (NPC) and analysed the factors affecting survival.
      DESIGN: A retrospective cohort study. SETTING: A nationwide population-based
      study in Taiwan. PARTICIPANTS: We identified 13 407 patients with newly diagnosed
      NPC from 2002 to 2010. MATERIAL AND METHODS: The multivariate Cox proportional
      hazards model was performed to measure the mortality-association risk factor in
      patients with NPC after adjusting for NPC treatment and socio-demographic
      characteristics. RESULTS: The 1-, 2-, 5- and 8-year overall survival (OS) rates
      were 89.6%, 80.4%, 65.2% and 56.5%, respectively. The factors associated with
      mortality risk were sex (men versus women, HR  =  1.45), age (>60 versus <= 40
      years, HR  =  3.61), geographic region of residence (eastern Taiwan versus
      northern Taiwan HR   =   1.39), income (<15 840 versus >25  000, HR   =   1.87)
      and treatment modality (chemotherapy alone versus radiotherapy alone, HR   =  
      2.25). CONCLUSION: The contemporary 5-year OS rate was 65.2% in Taiwan. Male
      patients, old age, residing in eastern Taiwan, low income and receiving
      chemotherapy alone were independent predictors for poor OS.

PMID- 25581516
TI  - Discrimination between Bacillus and Alicyclobacillus isolates in apple juice by
      Fourier transform infrared spectroscopy and multivariate analysis.
AB  - Alicyclobacillus is a causative agent of spoilage in pasteurized and heat-treated
      apple juice products. Differentiating between this genus and the closely related
      Bacillus is crucially important. In this study, Fourier transform infrared
      spectroscopy (FT-IR) was used to identify and discriminate between 4
      Alicyclobacillus strains and 4 Bacillus isolates inoculated individually into
      apple juice. Loading plots over the range of 1350 and 1700 cm(-1) reflected the
      most distinctive biochemical features of Bacillus and Alicyclobacillus.
      Multivariate statistical methods (for example, principal component analysis and
      soft independent modeling of class analogy) were used to analyze the spectral
      data. Distinctive separation of spectral samples was observed. This study
      demonstrates that FT-IR spectroscopy in combination with multivariate analysis
      could serve as a rapid and effective tool for fruit juice industry to
      differentiate between Bacillus and Alicyclobacillus and to distinguish between
      species belonging to these 2 genera. 

PMID- 25581514
TI  - Benefits and drawbacks of open partial horizontal laryngectomies, Part A: Early-
      to intermediate-stage glottic carcinoma.
AB  - BACKGROUND: Laryngeal squamous cell carcinoma (SCC) accounts for 1.9% of cancers
      worldwide. Most of these are diagnosed in the early stages (T1-T2, and N0). For
      these, a larynx preserving/conserving option is preferable. Beyond transoral
      laser microsurgery (TLM), open partial horizontal laryngectomy is a function
      sparing surgical technique used to treat laryngeal SCC. METHODS: We
      retrospectively analyzed the clinical outcomes of 216 patients who underwent open
      partial horizontal laryngectomy for glottic cT2 laryngeal cancer. RESULTS: Five
      year overall survival (OS), disease-specific survival (DFS), locoregional
      control, local control, laryngeal function preservation, and laryngectomy-free
      survival rates were 93.1%, 98.0%, 97.1%, 97.5%, 97.8%, and 98.5%, respectively.
      Disease controls were significantly affected by previous treatment and type of
      surgery used. CONCLUSION: Although TLM for cT2 laryngeal cancer with unimpaired
      vocal cord mobility still represents a sound option, open partial horizontal
      laryngectomy offers higher local control and laryngeal preservation rates for
      selected patients with impaired mobility of vocal cords combined with involvement
      of the paraglottic space. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E333
      E340, 2016.

PMID- 25581517
TI  - Orphan nuclear receptor NR4A1 regulates transforming growth factor-beta signaling
      and fibrosis.
AB  - Mesenchymal responses are an essential aspect of tissue repair. Failure to
      terminate this repair process correctly, however, results in fibrosis and organ
      dysfunction. Therapies that block fibrosis and restore tissue homeostasis are not
      yet available for clinical use. Here we characterize the nuclear receptor NR4A1
      as an endogenous inhibitor of transforming growth factor-beta (TGF-beta)
      signaling and as a potential target for anti-fibrotic therapies. NR4A1 recruits a
      repressor complex comprising SP1, SIN3A, CoREST, LSD1, and HDAC1 to TGF-beta
      target genes, thereby limiting pro-fibrotic TGF-beta effects. Even though
      temporary upregulation of TGF-beta in physiologic wound healing induces NR4A1
      expression and thereby creates a negative feedback loop, the persistent
      activation of TGF-beta signaling in fibrotic diseases uses AKT- and HDAC
      dependent mechanisms to inhibit NR4A1 expression and activation. Small-molecule
      NR4A1 agonists can overcome this lack of active NR4A1 and inhibit experimentally
      induced skin, lung, liver, and kidney fibrosis in mice. Our data demonstrate a
      regulatory role of NR4A1 in TGF-beta signaling and fibrosis, providing the first
      proof of concept for targeting NR4A1 in fibrotic diseases. 

PMID- 25581519
TI  - Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance
      in type 2 diabetes.
AB  - Type 2 diabetes is a major health problem worldwide, and one of its key features
      is the inability of elevated glucose to stimulate the release of sufficient
      amounts of insulin from pancreatic beta cells to maintain normal blood glucose
      levels. New therapeutic strategies to improve beta cell function are therefore
      believed to be beneficial. Here we demonstrate that the short-chain fatty acid
      receptors FFA2 (encoded by FFAR2) and FFA3 (encoded by FFAR3) are expressed in
      mouse and human pancreatic beta cells and mediate an inhibition of insulin
      secretion by coupling to Gi-type G proteins. We also provide evidence that mice
      with dietary-induced obesity and type 2 diabetes, as compared to non-obese
      control mice, have increased local formation by pancreatic islets of acetate, an
      endogenous agonist of FFA2 and FFA3, as well as increased systemic levels. This
      elevation may contribute to the insufficient capacity of beta cells to respond to
      hyperglycemia in obese states. Indeed, we found that genetic deletion of both
      receptors, either on the whole-body level or specifically in pancreatic beta
      cells, leads to greater insulin secretion and a profound improvement of glucose
      tolerance when mice are on a high-fat diet compared to controls. On the other
      hand, deletion of Ffar2 and Ffar3 in intestinal cells did not alter glucose
      tolerance in diabetic animals, suggesting these receptors act in a cell
      autonomous manner in beta cells to regulate insulin secretion. In summary, under
      diabetic conditions elevated acetate acts on FFA2 and FFA3 to inhibit proper
      glucose-stimulated insulin secretion, and we expect antagonists of FFA2 and FFA3
      to improve insulin secretion in type 2 diabetes. 

PMID- 25581518
TI  - Myeloid-derived growth factor (C19orf10) mediates cardiac repair following
      myocardial infarction.
AB  - Paracrine-acting proteins are emerging as a central mechanism by which bone
      marrow cell-based therapies improve tissue repair and heart function after
      myocardial infarction (MI). We carried out a bioinformatic secretome analysis in
      bone marrow cells from patients with acute MI to identify novel secreted proteins
      with therapeutic potential. Functional screens revealed a secreted protein
      encoded by an open reading frame on chromosome 19 (C19orf10) that promotes
      cardiac myocyte survival and angiogenesis. We show that bone marrow-derived
      monocytes and macrophages produce this protein endogenously to protect and repair
      the heart after MI, and we named it myeloid-derived growth factor (MYDGF).
      Whereas Mydgf-deficient mice develop larger infarct scars and more severe
      contractile dysfunction compared to wild-type mice, treatment with recombinant
      Mydgf reduces scar size and contractile dysfunction after MI. This study is the
      first to assign a biological function to MYDGF, and it may serve as a
      prototypical example for the development of protein-based therapies for ischemic
      tissue repair. 

PMID- 25581521
TI  - Decisions, decisions, decisions.

PMID- 25581520
TI  - Assessing scale-up of mHealth innovations based on intervention complexity: two
      case studies of child health programs in Malawi and Zambia.
AB  - As interest in mHealth (including Short Message Services or SMS) increases, it is
      important to assess potential benefits and limitations of this technology in
      improving interventions in resource-poor settings. The authors analyzed two case
      studies (early infant diagnosis of HIV and nutrition surveillance) of three
      projects in Malawi and Zambia using a conceptual framework that assesses the
      technical complexity of the programs, with and without the use of SMS technology.
      The authors based their findings on literature and discussions with key
      informants involved in the programs. For both interventions, introducing SMS
      reduced barriers to effective and timely delivery of services by simplifying the
      tracking and analysis of data and improving communication between healthcare
      providers. However, the primary implementation challenges for both interventions
      were related to broader program delivery characteristics (e.g., human resource
      needs and transportation requirements) that are not easily addressed by the
      addition of SMS. The addition of SMS technology itself introduced new layers of
      complexity. 

PMID- 25581522
TI  - HCAHPS Series Part 2: does purposeful leader rounding make a difference?

PMID- 25581523
TI  - Immunoscoring of epidermal growth factor receptor expression in recurrent cases
      of oral squamous cell carcinoma.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is a genetic disease with high
      prevalence and poor survival. Evaluation of recurrent tumor for a valid biomarker
      may serve as a predictive system for analyzing prognostic course of this disease.
      This study was designed to evaluate and compare the immunoscoring of epidermal
      growth factor receptor (EGFR) expression in recurrent cases with their matched
      regional/locoregional recurrence and non-recurrent cases of OSCC. METHODOLOGY: A
      total of 64 cases of OSCC were studied and immunostained with polyclonal EGFR
      antibody. Of these, 33 cases recurred at the end of 5 years of follow-up. For
      positive evaluation of EGFR staining, immunscoring was performed by adding the
      extent score and intensity score. RESULTS: We observed significant increase in
      EGFR immunoscore in recurrent cases of OSCC (P-value 0.001). Immunoscoring of
      EGFR expression is an independent prognostic and/or predictive parameter for
      recurrence in OSCC (Odds Ratio: 6.52). CONCLUSION: Immunoscore using EGFR can be
      incorporated into traditional classification, thus providing an essential
      prognostic and potentially predictive tool.

PMID- 25581525
TI  - Haemorrhagic complications with adenotonsillectomy in children and young adults
      with bleeding disorders.
AB  - Haemorrhagic complications remain a challenge with surgical procedures in
      patients with bleeding disorders. In children and young adults, the most commonly
      performed surgeries are tonsillectomies and/or adenoidectomies. Adequate
      haemostasis in these patients with bleeding disorders is centred on comprehensive
      perioperative haemostatic support and dexterous surgical technique. The aim of
      this study was to assess postoperative bleeding complications with tonsillectomy
      and/or adenoidectomy in children and young adults with known bleeding disorders.
      Retrospective review of all patients aged <25 years with known bleeding disorders
      who underwent tonsillectomy and/or adenoidectomy at Mayo Clinic, Rochester MN
      between July 1992 and July 2012. In contrast to reported literature, we observed
      a higher rate of bleeding complications (10/19, 53%) despite aggressive
      haemostatic support and appropriate surgical techniques. Delayed bleeding (>24 h
      postoperatively) was more common than early bleeding; and recurrent bleeding was
      associated with older age. Children and young adults with haemorrhagic diatheses
      undergoing adenotonsillectomy are at a higher risk of delayed bleeding and
      require close monitoring with haemostatic support for a prolonged duration in the
      postoperative period. A uniform approach is needed to manage these patients
      perioperatively by establishing standard practice guidelines and ultimately
      reduce postsurgical bleeding complications. 

PMID- 25581524
TI  - In vitro fermentation of total mixed diets differing in concentrate proportion:
      relative effects of inocula and substrates.
AB  - BACKGROUND: In vitro techniques are used to predict ruminant feedstuff values or
      characterise rumen fermentation. As the results are influenced by several
      factors, such as the relative effects of inocula and substrates, this study aimed
      to examine in vitro incubation of two total mixed rations (substrates) differing
      in their proportion of concentrate [low (L): 350 g kg(-1) vs. high (H): 700 g kg(
      1)] incubated in inocula provided by goats fed either a L or a H diet. Gas
      production and composition in carbon dioxide (CO2), methane (CH4 ) and hydrogen
      (H2), volatile fatty acids (VFAs), soluble carbohydrates (SCs) and ammonia (NH3)
      concentrations, and pH of the fermentation fluid were measured. RESULTS: In
      comparison with the L inoculum and L substrate, the H ones produced more CO2 and
      CH4 gas, which led to higher SCs and VFA concentrations, and lower acetate-to
      propionate ratio and NH3 concentration, with a predominant effect of the
      inoculum. CONCLUSION: The effects of the inocula and of the substrates were
      additive using donor animals adapted to the diets.

PMID- 25581526
TI  - Size and molecular flexibility of sugars determine the storage stability of
      freeze-dried proteins.
AB  - Protein-based biopharmaceuticals are generally produced as aqueous solutions and
      stored refrigerated to obtain sufficient shelf life. Alternatively, proteins may
      be freeze-dried in the presence of sugars to allow storage stability at ambient
      conditions for prolonged periods. However, to act as a stabilizer, these sugars
      should remain in the glassy state during storage. This requires a sufficiently
      high glass transition temperature (Tg). Furthermore, the sugars should be able to
      replace the hydrogen bonds between the protein and water during drying.
      Frequently used disaccharides are characterized by a relatively low Tg, rendering
      them sensitive to plasticizing effects of residual water, which strongly reduces
      the Tg values of the formulation. Larger sugars generally have higher Tgs, but it
      is assumed that these sugars are limited in their ability to interact with the
      protein due to steric hindrance. In this paper, the size and molecular
      flexibility of sugars was related to their ability to stabilize proteins. Four
      diverse proteins varying in size from 6 kDa to 540 kDa were freeze-dried in the
      presence of different sugars varying in size and molecular flexibility.
      Subsequently, the different samples were subjected to an accelerated stability
      test. Using protein specific assays and intrinsic fluorescence, stability of the
      proteins was monitored. It was found that the smallest sugar (disaccharide
      trehalose) best preserved the proteins, but also that the Tg of the formulations
      was only just high enough to maintain sufficient vitrification. When trehalose
      based formulations are exposed to high relative humidities, water uptake by the
      product reduces the Tgs too much. In that respect, sugars with higher Tgs are
      desired. Addition of polysaccharide dextran 70 kDa to trehalose greatly increased
      the Tg of the formulation. Moreover, this combination also improved the stability
      of the proteins compared to dextran only formulations. The molecularly flexible
      oligosaccharide inulin 4 kDa provided better stabilization than the similarly
      sized but molecularly rigid oligosaccharide dextran 6 kDa. In conclusion, the
      results of this study indicate that size and molecular flexibility of sugars
      affect their ability to stabilize proteins. As long as they maintain vitrified,
      smaller and molecularly more flexible sugars are less affected by steric
      hindrance and thus better capable at stabilizing proteins. 

PMID- 25581528
TI  - Environmental and ecological interactions.

PMID- 25581531
TI  - The Effect of Pollination on Cd Phytoextraction From Soil by Maize (Zea mays L.).
AB  - A pot experiment was conducted to investigate the effects of pollination on
      cadmium (Cd) phytoextraction from soil by mature maize plants. The results showed
      that the unpollinated maize plants accumulated 50% more Cd than that of the
      pollinated plants, even though the dry weight of the former plants was 15% less
      than that of the latter plants. The Cd accumulation in root and leaf of the
      unpollinated maize plant was 0.47 and 0.89 times higher than that of the
      pollinated plant, respectively. The Cd concentration in the cob was significantly
      decreased because of pollination. Preventing pollination is a promising approach
      for enhancing the effectiveness of phytoextraction in Cd-contaminated soils by
      maize. This study suggested that in low Cd-contaminated soil pollination should
      be encouraged because accumulation of Cd in maize grains is very little and maize
      seeds can bring farmers economic benefits, while in high Cd-contaminated soil,
      inhibition of pollination can be applied to enhance phytoextraction of Cd from
      soil by maize plant.

PMID- 25581527
TI  - Analyzing insulin samples by size-exclusion chromatography: a column degradation
      study.
AB  - Investigating insulin analogs and probing their intrinsic stability at
      physiological temperature, we observed significant degradation in the size
      exclusion chromatography (SEC) signal over a moderate number of insulin sample
      injections, which generated concerns about the quality of the separations.
      Therefore, our research goal was to identify the cause(s) for the observed signal
      degradation and attempt to mitigate the degradation in order to extend SEC column
      lifespan. In these studies, we used multiangle light scattering, nuclear magnetic
      resonance, and gas chromatography-mass spectrometry methods to evaluate column
      degradation. The results from these studies illustrate: (1) that zinc ions
      introduced by the insulin product produced the observed column performance
      issues; and (2) that including ethylenediaminetetraacetic acid, a zinc chelator,
      in the mobile phase helped to maintain column performance.

PMID- 25581533
TI  - Human vaccines & immunotherapeutics: news.

PMID- 25581532
TI  - Erythropoietin pretreatment ameliorates renal ischaemia-reperfusion injury by
      activating PI3K/Akt signalling.
AB  - AIM: Renal ischaemia-reperfusion (I/R) injury, a primary cause of acute renal
      failure, can induce high morbidity and mortality. This study aimed to explore the
      effect of erythropoietin on renal I/R injury and its underlying mechanism.
      METHODS: Fifty male Sprague-Dawley rats were randomly allocated to three groups
      (n = 10): the sham group, the renal ischaemia-reperfusion-saline (IRI) group, and
      the IRI+-Erythropoietin (EPO) group. Erythropoietin (250, 500, 1000 U/kg) was
      intraperitoneally injected 30 min before inducing I/R. Renal I/R injury were
      induced by clamping the left renal artery for 30 min followed by reperfusion,
      along with a contralateral nephrectomy. Renal function and histological damage
      were determined after 24 h reperfusion. The expression of pro-inflammatory
      cytokines interleukin-6 (IL-6), interleukin-1 beta (IL-1beta), and tumour
      necrosis factor-alpha (TNF-alpha) in the serum and renal tissue were evaluated by
      enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase
      chain reaction (RT-PCR), respectively. Further, the effects of erythropoietin on
      PI3K/Akt signalling, erythropoietin receptor (EPOR) and nuclear factor (NF)
      kappaB activation were measured by Western blotting. RESULTS: Erythropoietin
      pretreatment can significantly decrease the level of renal dysfunction in a dose
      dependent manner, attenuated the renal histological changes, the expression of
      TNF-alpha, IL-1beta, and IL-6, the levels of reactive oxygen species (ROS)
      production and NF-kappaB p65 phosphorylation in renal tissue upon IRI. Moreover,
      erythropoietin pretreatment could further activate the PI3K/Akt signalling and
      induced EPOR activity. CONCLUSIONS: Erythropoietin pretreatment could attenuate
      renal I/R injury by suppressing inflammation, which was associated with
      activating PI3K/Akt signalling though EPOR activation. Our findings suggest that
      erythropoietin may be a novel practical strategy to prevent renal I/R injury.

PMID- 25581534
TI  - Vaccination in HIV positive adults: need to address.
AB  - Human Immunodeficiency Virus (HIV) continues to be a major public health program.
      Without treatment, average survival time without treatment after infection with
      HIV is estimated to be 9 to 11 years, depending on the HIV subtype. Vaccination
      recommendations are determined by weighing the benefits of vaccination against
      the risks. It is preferable to have patients on antiretroviral therapy (ART)
      prior to receipt of vaccination, as that may help blunt or eliminate vaccine
      associated viremia and potentially improve immune response to vaccination. :
      Although data are limited, in general, HIV-infected individuals who are on ART
      with well-controlled HIV RNA levels and CD4 counts of >200 cells/MUL (or = 15%)
      may receive indicated live-virus vaccines. Vaccination can play a vital role in
      enhancing the immunity against opportunistic infections. Further research, is the
      need for a better and healthy living of the people with HIV.

PMID- 25581536
TI  - Differentiating benign from malignant mediastinal lymph nodes visible at EBUS
      using grey-scale textural analysis.
AB  - BACKGROUND AND OBJECTIVE: Recent data suggest that grey-scale textural analysis
      on endobronchial ultrasound (EBUS) imaging can differentiate benign from
      malignant lymphadenopathy. The objective of studies was to evaluate grey-scale
      textural analysis and examine its clinical utility. METHODS: Images from 135
      consecutive clinically indicated EBUS procedures were evaluated retrospectively
      using MATLAB software (MathWorks, Natick, MA, USA). Manual node mapping was
      performed to obtain a region of interest and grey-scale textural features (range
      of pixel values and entropy) were analysed. The initial analysis involved 94
      subjects and receiver operating characteristic (ROC) curves were generated. The
      ROC thresholds were then applied on a second cohort (41 subjects) to validate the
      earlier findings. RESULTS: A total of 371 images were evaluated. There was no
      difference in proportions of malignant disease (56% vs 53%, P = 0.66) in the
      prediction (group 1) and validation (group 2) sets. There was no difference in
      range of pixel values in group 1 but entropy was significantly higher in the
      malignant group (5.95 vs 5.77, P = 0.03). Higher entropy was seen in
      adenocarcinoma versus lymphoma (6.00 vs 5.50, P < 0.05). An ROC curve for entropy
      gave an area under the curve of 0.58 with 51% sensitivity and 71% specificity for
      entropy greater than 5.94 for malignancy. In group 2, the entropy threshold
      phenotyped only 47% of benign cases and 20% of malignant cases correctly.
      CONCLUSIONS: These findings suggest that use of EBUS grey-scale textural analysis
      for differentiation of malignant from benign lymphadenopathy may not be accurate.
      Further studies are required.

PMID- 25581535
TI  - Meeting report VLPNPV: Session 5: Plant based technology.
AB  - The VLPNPV 2014 Conference that was convened at the Salk institute was the second
      conference of its kind to focus on advances in production, purification, and
      delivery of virus-like particles (VLPs) and nanoparticles. Many exciting
      developments were reported and discussed in this interdisciplinary arena, but
      here we report specifically on the contributions of plant-based platforms to VLP
      vaccine technology as reported in the section of the conference devoted to the
      topic as well in additional presentations throughout the meeting. The increasing
      popularity of plant production platforms is due to their lower cost, scalability,
      and lack of contaminating animal pathogens seen with other systems. Reports
      include production of complex VLPs consisting of 4 proteins expressed at finely
      tuned expression levels, a prime-boost strategy for HIV vaccination using plant
      made VLPs and a live viral vector, and the characterization and development of
      plant viral nanoparticles for use in cancer vaccines, drug delivery, and
      bioimaging. 

PMID- 25581537
TI  - Organ-sparing surgery in urology: partial cystectomy.
AB  - PURPOSE OF REVIEW: While radical cystectomy continues to be the gold standard for
      surgical management of muscle invasive bladder cancer, there has been a renewed
      interest in partial cystectomy as a viable treatment alternative. The purpose of
      this review is to summarize and discuss the recent literature regarding partial
      cystectomy for bladder cancer. RECENT FINDINGS: Utilization of partial cystectomy
      has remained stable, at a rate of 7-10% of all cystectomies performed nationally.
      Additionally, recent population-based series as well as single institution
      cohorts have found that partial cystectomy did not compromise survival when
      compared to radical cystectomy. While patients may recur, those with organ
      confined disease had no difference in survival following salvage cystectomy when
      compared to primary radical cystectomy. Current data indicate 14% of patients
      experience an in-hospital complication, which is a marked decrease compared to
      radical cystectomy. Finally, innovations in surgical technique, such as robotics,
      as well as the inclusion of partial cystectomy into trimodal therapy, offer
      exciting new frontiers in bladder cancer treatment. SUMMARY: Once maligned,
      partial cystectomy now represents a standard-of-care option for management of
      bladder cancer. Although additional research is needed to clarify patient
      selection and outcomes, partial cystectomy is an important treatment option for
      appropriately selected patients.

PMID- 25581538
TI  - Female reproductive organ-sparing radical cystectomy: contemporary indications,
      techniques and outcomes.
AB  - PURPOSE OF REVIEW: Surgical techniques to spare female reproductive organs at the
      time of radical cystectomy [reproductive organ-sparing radical cystectomy
      (ROSRC)] have been advocated to improve quality of life with respect to sexual
      and urinary function. These potential benefits must be weighed against the risk
      of inappropriate patient selection and related oncologic risk. RECENT FINDINGS:
      In this review, we describe the evidence to define the appropriate selection
      criteria to minimize clinical understaging. The literature provides small cohorts
      with intermediate-term follow-up to support oncologic safety, and thus ROSRC must
      continue to be evaluated with long-term studies. Pertinent techniques for ROSRC
      are described based on underlying anatomic principles. Lastly, studies on the
      potential sexual and urinary functional advantages are promising, but must be
      evaluated in light of the excellent baseline functional characteristics of those
      selected for inclusion. SUMMARY: ROSRC appears to provide measurable benefits to
      sexual and urinary function. However, the magnitude of these benefits is unclear
      and the selection of appropriate candidates requires further prospective study
      vis-a-vis oncologic control. ROSRC must be adopted cautiously until further data
      are available.

PMID- 25581539
TI  - Role of transurethral resection of the prostate simulators for training in
      transurethral surgery.
AB  - PURPOSE OF REVIEW: Transurethral surgery is an art unique to urologists;
      mastering the craft is essential for day-to-day practice. Medical treatment along
      with minimally invasive treatments have significantly reduced the number of
      transurethral resection of prostates. Decrease in resident's training hours,
      expanding subspecialties and the emergence of newer technologies have burdened
      the trainees who are trying to digest the ever-expanding medical literature.
      Moreover, expectations from patients and insurance companies with a stress on
      cutting costs and raising litigations have brought changes in apprentice-based to
      simulator-based training. We studied the role of transurethral resection of
      prostate simulators in training of transurethral surgery. RECENT FINDINGS: TURP
      simulators from bench to virtual reality computer models are available. Most of
      them have undergone face, content and construct validity. Nontechnical skills
      training is also important hence simulation to simulator training. Simulation
      programmes incorporating communication, team building, minimizing errors caused
      by distraction and managing complex situations can turn a novice into an expert
      with adequate practice in a stress-free environment. Work is also done to define
      learning curve, and factors affecting the path to reach the desired goal.
      Concepts are emerging to integrate simulators and simulation into the existing
      training programmes. SUMMARY: TURP simulators are essential for training in
      transurethral surgery. Low or high-fidelity simulators do not matter, but having
      a well structured simulation programme, under the scrutiny of a dedicated trained
      faculty, will address most of the issues related to training in transurethral
      surgery, an art essential for urologists irrespective of the subspecialty one
      pursues in the future.

PMID- 25581540
TI  - Current trends in partial adrenalectomy.
AB  - PURPOSE OF REVIEW: Total adrenalectomy has been the standard treatment for small
      adrenal masses for years. In recent times, however, partial adrenalectomy and
      cortex-preserving strategies are gaining more importance. Therefore, we evaluated
      indications, techniques and outcome of partial adrenalectomy. RECENT FINDINGS:
      With more small adrenal masses identified through the widespread use of imaging
      modalities, partial adrenalectomy and cortical-preserving strategies were applied
      in various indications and techniques. In all original papers published on this
      topic during the review period of the last 18 months, minimal invasive approaches
      were used with satisfying surgical and functional outcomes. SUMMARY: There is a
      definitive trend towards the use of partial adrenalectomy in the treatment of
      small adrenal masses. In bilateral disease, steroid replacement can be avoided in
      most cases, whereas successful normalization of pathological endocrine levels was
      reported in various indications. Therefore, minimal invasive partial
      adrenalectomy may become the recommended standard treatment of small benign and
      hormonal active adrenal tumours.

PMID- 25581541
TI  - Chicken and porcine models for training in laparoscopy and robotics.
AB  - PURPOSE OF REVIEW: To review the most recent literature and contemporary role of
      the use of porcine and chicken models in laparoscopic and robotic simulation
      exercises, for training and skill assessment. RECENT FINDINGS: There are multiple
      types of the simulators which include mechanical, virtual reality, hybrid
      simulators and animal models. The recent literature has seen insurgence of
      several of such simulators, specifically the animate ones comprising porcine and
      chicken models. The different training models reported have evolved from
      generalized and simpler, to a more task dedicated and complex versions. Unlike in
      the past, the recent publications include analysis of these models incorporating
      different measures of validity assessment. SUMMARY: On account of the natural
      tissue properties inherent to these porcine and chicken models, they are proving
      to be instrumental in acquisition of higher surgical skills such as dissection,
      suturing and use of energy sources, all of which are required in real-time
      clinical scenarios be it laparoscopy or robotic-assisted procedures. In-vivo
      training in the animal model continues to be, perhaps, the most sophisticated
      training method before resorting to real-time surgery.

PMID- 25581542
TI  - Kidney-sparing surgery for upper tract urothelial cancer.
AB  - PURPOSE OF REVIEW: This article reviews and summarizes current knowledge on
      kidney-sparing surgery (KSS) for upper tract urothelial carcinoma (UTUC). RECENT
      FINDINGS: Radical nephroureterectomy (RNU) has been central to the treatment of
      UTUC for decades, but KSS has been applied to a rising number of patients to
      preserve renal function. Ablation or resection through flexible ureteroscopy or
      the percutaneous route seems to provide comparable cancer-specific survival and
      overall survival to RNU, but the risk of local and bladder recurrence remains
      relatively high. Segmental ureterectomy is used for low-risk unifocal UTUC with
      recent studies confirming its oncologic safety and equivalence to RNU. Antegrade
      or retrograde instillation therapy may be considered as adjuvant treatment after
      conservative surgery, but their efficacy needs to be proven. Intravesical single
      dose chemotherapy is likely to become part of the therapy algorithm of UTUC
      treated by KSS or RNU to lower bladder seeding and recurrence. Postoperative
      vigilant radiographic and endoscopic surveillance are obligatory because of the
      high probability of recurrence. SUMMARY: KSS should be regarded as a valid
      alternative to RNU in case of technically resectable low-risk upper tract
      urothelial cell carcinoma, even in case of a normal contralateral kidney.
      Advances in technology and biological and clinical risk estimation will make the
      management of UTUC more evidence based thereby lowering overtreatment.

PMID- 25581543
TI  - Lymphadenectomy for testicular, penile, upper tract urothelial and urethral
      cancers.
AB  - PURPOSE OF REVIEW: The lymph node dissection (LND) is an integral component of
      many oncologic surgeries. Better understanding of each cancer's behaviour and
      improvements in surgical techniques necessitate a critical analysis of lymph node
      disease and the optimal LND template. This review will focus on updates in
      managing lymph node disease in testicular, penile, upper tract urothelial and
      urethral cancer. RECENT FINDINGS: For testicular and penile cancer, advances have
      focused on reducing the morbidity associated with the standard templates of
      dissection while maintaining oncologic efficacy. For upper tract urothelial
      carcinoma, data continue to be mixed regarding the need for a LND, though it does
      seem to benefit patients with advanced tumours. Little is known regarding the
      optimal LND template for urethral cancer. SUMMARY: A thorough LND has an
      established diagnostic and therapeutic role in testicular and penile cancer. For
      upper tract urothelial carcinoma, the role of an LND remains controversial,
      though emerging evidence points to an association with improved outcomes. Due to
      the rarity of urethral cancer, there are no standard LND templates, though
      excising clinically positive nodes is recommended. For all these cancers, more
      sophisticated risk stratification based upon clinical and pathologic factors has
      helped determine which patients require an LND and how to best manage these
      patients after surgery.

PMID- 25581544
TI  - Organ-sparing surgery for testicular tumours.
AB  - PURPOSE OF REVIEW: Testicular cancer represents the majority of testicular
      masses, and radical orchiectomy is still considered the standard-of-care. Testis
      sparing surgery (TSS) can be an alternative to radical surgery in patients with
      small testicular tumours, bilateral or solitary testis masses. The aim of this
      manuscript is to review the current indications, oncological and functional
      outcomes of TSS. RECENT FINDINGS: Our review confirmed that literature lacks
      studies with a high level of evidence on comparing TSS with radical surgery.
      Indications for TSS are controversial, specifically for patients with normal
      contralateral testis. For nonpalpable testicular masses less than 2 cm, bilateral
      tumours and solitary testis mass, TSS seems to be a viable treatment option.
      Frozen-section examination is a critical tool for assessment at the time of TSS
      that allows for diagnosis of benign from malignant tumours and evaluation of
      margin. TSS has been shown to be associated with less fertility alterations,
      hormonal deficit and potential lower impact on sexual and psychosocial aspects.
      Intermediate to long-term follow-up results have not revealed any significant
      risk of local and/or distant recurrences after TSS. SUMMARY: TSS is well
      tolerated and feasible for selected patients with testicular mass without
      compromising oncological and functional outcomes. Further studies with a higher
      level of evidence are needed to confirm these findings.

PMID- 25581545
TI  - Glycaemic control and self-management behaviours in Type 2 diabetes: results from
      a 1-year longitudinal cohort study.
AB  - AIM: To better understand the associations between changes in self-management
      behaviours and glycaemic control. METHODS: We conducted a prospective
      observational study of 295 adult patients with Type 2 diabetes evaluated at
      baseline, 6 and 12 months. Four self-management behaviours were evaluated using
      the Summary of Diabetes Self-Care Activities instrument, which assesses healthy
      diet, physical activity, medication taking and self-monitoring of blood glucose.
      Using hierarchical linear regression models, we tested whether changes in self
      management behaviours were associated with short-term (6-month) or long-term (12
      month) changes in glycaemic control, after controlling for demographic and
      clinical characteristics. RESULTS: Improved diet was associated with a decrease
      in HbA1c level, both at 6 and 12 months. Improved medication taking was
      associated with short-term improvement in glycaemic control, while increased self
      monitoring of blood glucose frequency was associated with a 12-month improvement
      in HbA1c . Completely stopping exercise after being physically active at baseline
      was associated with a rise in HbA1c level at 6-month follow-up. Interaction
      analysis indicated that a healthy diet benefitted all participant subgroups, but
      that medication taking was associated with glycaemic control only for
      participants living in poverty and more strongly for those with lower educational
      levels. Finally, a higher self-monitoring of blood glucose frequency was
      associated with better glycaemic control only in insulin-treated participants.
      CONCLUSIONS: Even after adjusting for potential confounders (including baseline
      HbA1c ), increased frequency of healthy diet, medication taking and self
      monitoring of blood glucose were associated with improved HbA1c levels. These
      self-management behaviours should be regularly monitored to identify patients at
      risk of deterioration in glycaemic control. Barriers to optimum self-management
      should be removed, particularly among socio-economically disadvantaged
      populations.

PMID- 25581546
TI  - Aberrant NMDA-dependent LTD after perinatal ethanol exposure in young adult rat
      hippocampus.
AB  - Irreversible cognitive deficits induced by ethanol exposure during fetal life
      have been ascribed to a lower NMDA-dependent synaptic long-term potentiation
      (LTP) in the hippocampus. Whether NMDA-dependent long-term depression (LTD) may
      also play a critical role in those deficits remains unknown. Here, we show that
      in vitro LTD induced with paired-pulse low frequency stimulation is enhanced in
      CA1 hippocampus field of young adult rats exposed to ethanol during brain
      development. Furthermore, single pulse low frequency stimulation, ineffective at
      this age (LFS600), induced LTD after ethanol exposure accompanied with a stronger
      response than controls during LFS600, thus revealing an aberrant form of activity
      dependent plasticity at this age. Blocking NMDA receptor or GluN2B containing
      NMDA receptor prevented both the stronger response during LFS600 and LTD whereas
      Zinc, an antagonist of GluN2A containing NMDA receptor, was ineffective on both
      responses. In addition, LFS600-induced LTD was revealed in controls only with a
      reduced-Mg(2+) medium. In whole dissected hippocampus CA1 field, perinatal
      ethanol exposure increased GluN2B subunit expression in the synaptic compartment
      whereas GluN2A was unaltered. Using pharmacological tools, we suggest that LFS600
      LTD was of synaptic origin. Altogether, we describe a new mechanism by which
      ethanol exposure during fetal life induces a long-term alteration of synaptic
      plasticity involving NMDA receptors, leading to an aberrant LTD. We suggest this
      effect of ethanol may reflect a delayed maturation of the synapse and that
      aberrant LTD may also participates to long-lasting cognitive deficits in fetal
      alcohol spectrum disorder.

PMID- 25581548
TI  - Rapid metabolite discovery, identification, and accurate comparison of the
      stereoselective metabolism of metalaxyl in rat hepatic microsomes.
AB  - Metabolite identification and quantitation impose great challenges on risk
      assessment of agrochemicals, as many metabolite standards are generally
      unavailable. In this study, metalaxyl metabolites were identified by time-of
      flight mass spectrometry and semiquantified by triple quadrupole tandem mass
      spectrometry with self-prepared (13)C-labeled metalaxyl metabolites as internal
      standards. Such methodology was employed to characterize the stereoselective
      metabolism of metalaxyl in rat hepatic microsomes successfully. Metabolites
      derived from hydroxylation, demethylation, and didemethylation were identified
      and semiquantified. The results indicated that (+)-S-metalaxyl eliminated
      preferentially as the enantiomer fraction was 0.32 after 60 min incubation. The
      amounts of hydroxymetalaxyl and demethylmetalaxyl derived from (-)-R-metalaxyl
      were 1.76 and 1.82 times higher than that of (+)-S-metalaxyl, whereas
      didemethylmetalaxyl derived from (+)-S-metalaxyl was 1.44 times larger than that
      from (-)-R-metalaxyl. This study highlights a new quantitation approach for
      stereoselective metabolism of chiral agrochemicals and provides more knowledge on
      metalaxyl risk assessment. 

PMID- 25581549
TI  - Cementless total hip replacement complications.

PMID- 25581547
TI  - Lipid-specific immunoglobulin M bands in cerebrospinal fluid are associated with
      a reduced risk of developing progressive multifocal leukoencephalopathy during
      treatment with natalizumab.
AB  - OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is a serious side
      effect associated with natalizumab treatment in multiple sclerosis (MS). PML risk
      increases in individuals seropositive for anti-John Cunningham virus (JC)
      antibodies, with prolonged duration of natalizumab treatment, and with prior
      exposure to immunosuppressants. We explored whether the presence of lipid
      specific immunoglobulin M oligoclonal bands in cerebrospinal fluid (CSF; IgM
      bands), a recognized marker of highly inflammatory MS, may identify individuals
      better able to counteract the potential immunosuppressive effect of natalizumab
      and hence be associated with a reduced risk of developing PML. METHODS: We
      studied 24 MS patients who developed PML and another 343 who did not suffer this
      opportunistic infection during natalizumab treatment. Patients were recruited at
      25 university hospitals. IgM bands were studied by isoelectric focusing and
      immunodetection. CSF lymphocyte counts were explored in 151 MS patients recruited
      at Ramon y Cajal Hospital in Madrid, Spain. RESULTS: IgM bands were independently
      associated with decreased PML risk (odds ratio [OR] = 45.9, 95% confidence
      interval [CI] = 5.9-339.3, p < 0.0001) in patients treated with natalizumab. They
      were also associated with significantly higher CSF CD4, CD8, and B-cell numbers.
      Patients positive for IgM bands and anti-JC antibodies had similar levels of
      reduced PML risk to those who were anti-JC negative (OR = 1.55, 95% CI = 0.09
      25.2, p = 1.0). Higher risk was observed in patients positive for anti-JC
      antibodies and negative for IgM bands (19% of the total cohort, OR = 59.71, 95%
      CI = 13.6-262.2). INTERPRETATION: The presence of IgM bands reflects a process
      that may diminish the risk of PML by counteracting the excess of
      immunosuppression that may occur during natalizumab therapy.

PMID- 25581550
TI  - Morphogen transport: theoretical and experimental controversies.
AB  - According to morphogen gradient theory, extracellular ligands produced from a
      localized source convey positional information to receiving cells by signaling in
      a concentration-dependent manner. How do morphogens create concentration
      gradients to establish positional information in developing tissues?
      Surprisingly, the answer to this central question remains largely unknown. During
      development, a relatively small number of morphogens are reiteratively deployed
      to ensure normal embryogenesis and organogenesis. Thus, the intracellular
      processing and extracellular transport of morphogens are tightly regulated in a
      tissue-specific manner. Over the past few decades, diverse experimental and
      theoretical approaches have led to numerous conflicting models for gradient
      formation. In this review, we summarize the experimental evidence for each model
      and discuss potential future directions for studies of morphogen gradients. For
      further resources related to this article, please visit the WIREs website.
      CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this
      article.

PMID- 25581552
TI  - In vitro biodegradation behavior, mechanical properties, and cytotoxicity of
      biodegradable Zn-Mg alloy.
AB  - Zinc-Magnesium (Zn-Mg) alloy as a novel biodegradable metal holds great potential
      in biodegradable implant applications as it is more corrosion resistant than
      Magnesium (Mg). However, the mechanical properties, biodegradation uniformity,
      and cytotoxicity of Zn-Mg alloy remained as concerns. In this study, hot
      extrusion process was applied to Zn-1 wt % Mg (Zn-1Mg) to refine its
      microstructure. Effects of hot extrusion on biodegradation behavior and
      mechanical properties of Zn-1Mg were investigated in comparison with Mg rare
      earth element alloy WE43. Metallurgical analysis revealed significant grain size
      reduction, and immersion test found that corrosion rates of WE43 and Zn-1Mg were
      reduced by 35% and 57%, respectively after extrusion. Moreover, hot extrusion
      resulted in a much more uniform biodegradation in extruded Zn-1Mg alloy and WE43.
      In vitro cytotoxicity test results indicated that Zn-1Mg alloy was biocompatible.
      Therefore, hot extruded Zn-1Mg with homogenous microstructure, uniform as well as
      slow degradation, improved mechanical properties, and good biocompatibility was
      believed to be an excellent candidate material for load-bearing biodegradable
      implant application.

PMID- 25581553
TI  - South Texas Residency Screening, Brief Intervention, and Referral to Treatment
      (SBIRT) Training: 12-Month Outcomes.
AB  - BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) is
      an efficacious and cost-effective skill set when implemented in primary care
      settings regarding hazardous alcohol use. This study assesses the impact of
      medical resident SBIRT training across 3 specialties and identifies predictors of
      change in trainee behavior, attitudes, and knowledge over 12 months. METHODS:
      This program's substance use SBIRT training was developed and tailored to fit
      diverse curricular objectives and settings across an array of medical residency
      programs in South Texas. The 329 residents training in pediatrics, family
      medicine, and internal medicine during 2009-2012 constituted the trainee group
      reported in this analysis. Surveys assessing SBIRT-related knowledge, current
      practice, confidence, role responsibility, attitudes, beliefs, and readiness to
      change were completed by 234 (71%) trainees at 3 time points: pre-training, then
      30 days and 12 months post-initial training. RESULTS: SBIRT-related knowledge,
      confidence, and practice increased from pre-training to 12-month follow-up.
      Residents who reported the least amount of pre-training clinical and/or prior
      academic exposure to substance use reported the greatest SBIRT practice
      increases. When controlling for demographic and prior exposure variables, the
      largest contributor to variance in SBIRT practice was attributed to residents'
      confidence in their SBIRT skills. CONCLUSIONS: SBIRT training that employs
      diverse educational methodologies as part of customizing the training to
      residency specialties can similarly enhance SBIRT-related knowledge, confidence,
      and practice. Trainee report of limited prior clinical or academic exposure to
      substance use and/or low confidence regarding SBIRT skills and their professional
      role responsibilities related to substance use predicted trainee success and
      sustained SBIRT strategy application. When customizing SBIRT training, curriculum
      developers should consider leveraging and capacity building related to those
      factors predicting continued use of SBIRT practices.

PMID- 25581551
TI  - A rodent model of traumatic stress induces lasting sleep and quantitative
      electroencephalographic disturbances.
AB  - Hyperarousal and sleep disturbances are common, debilitating symptoms of post
      traumatic stress disorder (PTSD). PTSD patients also exhibit abnormalities in
      quantitative electroencephalography (qEEG) power spectra during wake as well as
      rapid eye movement (REM) and non-REM (NREM) sleep. Selective serotonin reuptake
      inhibitors (SSRIs), the first-line pharmacological treatment for PTSD, provide
      modest remediation of the hyperarousal symptoms in PTSD patients, but have little
      to no effect on the sleep-wake architecture deficits. Development of novel
      therapeutics for these sleep-wake architecture deficits is limited by a lack of
      relevant animal models. Thus, the present study investigated whether single
      prolonged stress (SPS), a rodent model of traumatic stress, induces PTSD-like
      sleep-wake and qEEG spectral power abnormalities that correlate with changes in
      central serotonin (5-HT) and neuropeptide Y (NPY) signaling in rats. Rats were
      implanted with telemetric recording devices to continuously measure EEG before
      and after SPS treatment. A second cohort of rats was used to measure SPS-induced
      changes in plasma corticosterone, 5-HT utilization, and NPY expression in brain
      regions that comprise the neural fear circuitry. SPS caused sustained
      dysregulation of NREM and REM sleep, accompanied by state-dependent alterations
      in qEEG power spectra indicative of cortical hyperarousal. These changes
      corresponded with acute induction of the corticosterone receptor co-chaperone
      FK506-binding protein 51 and delayed reductions in 5-HT utilization and NPY
      expression in the amygdala. SPS represents a preclinical model of PTSD-related
      sleep-wake and qEEG disturbances with underlying alterations in neurotransmitter
      systems known to modulate both sleep-wake architecture and the neural fear
      circuitry. 

PMID- 25581554
TI  - Does the pressure dependence of kinetic isotope effects report usefully on
      dynamics in enzyme H-transfer reactions?
AB  - The temperature dependence of kinetic isotope effects (KIEs) has emerged as the
      main experimental probe of enzymatic H-transfer by quantum tunnelling. Implicit
      in the interpretation is a presumed role for dynamic coupling of H-transfer
      chemistry to the protein environment, the so-called 'promoting motions/vibrations
      hypothesis'. This idea remains contentious, and others have questioned the
      importance and/or existence of promoting motions/vibrations. New experimental
      methods of addressing this problem are emerging, including use of mass-modulated
      enzymes and time-resolved spectroscopy. The pressure dependence of KIEs has been
      considered as a potential probe of quantum tunnelling reactions, because semi
      classical KIEs, which are defined by differences in zero-point vibrational
      energy, are relatively insensitive to kbar changes in pressure. Reported combined
      pressure and temperature (p-T) dependence studies of H-transfer reactions are,
      however, limited. Here, we extend and review the available p-T studies that have
      utilized well-defined experimental systems in which quantum mechanical tunnelling
      is established. These include flavoproteins, quinoproteins, light-activated
      enzymes and chemical model systems. We show that there is no clear general trend
      between the p-T dependencies of the KIEs in these systems. Given the complex
      nature of p-T studies, we conclude that computational simulations using
      determined (e.g. X-ray) structures are also needed alongside experimental
      measurements of reaction rates/KIEs to guide the interpretation of p-T effects.
      In providing new insight into H-transfer/environmental coupling, combined
      approaches that unite both atomistic understanding with experimental rate
      measurements will require careful evaluation on a case-by-case basis. Although
      individually informative, we conclude that p-T studies do not provide the more
      generalized insight that has come from studies of the temperature dependence of
      KIEs. 

PMID- 25581555
TI  - Hydrogen atom abstraction from hydrocarbons by a copper(III)-hydroxide complex.
AB  - With the aim of understanding the basis for the high rate of hydrogen atom
      abstraction (HAT) from dihydroanthracene (DHA) by the complex LCuOH (1; L = N,N'
      bis(2,6-diisopropylphenyl)-2,6-pyridinedicarboxamide), the bond dissociation
      enthalpy of the reaction product LCu(H2O) (2) was determined through measurement
      of its pK(a) and E(1/2) in THF solution. In so doing, an equilibrium between 2
      and LCu(THF) was characterized by UV-vis and EPR spectroscopy and cyclic
      voltammetry (CV). A high pK(a) of 18.8 +/- 1.8 and a low E(1/2) of -0.074 V vs
      Fc/Fc(+) in THF combined to yield an O-H BDE for 2 of 90 +/- 3 kcal mol(-1) that
      is large relative to values for most transition metal oxo/hydroxo complexes. By
      taking advantage of the increased stability of 1 observed in 1,2-difluorobenzene
      (DFB) solvent, the kinetics of the reactions of 1 with a range of substrates with
      varying BDE values for their C-H bonds were measured. The oxidizing power of 1
      was revealed through the accelerated decay of 1 in the presence of the
      substrates, including THF (BDE = 92 kcal mol(-1)) and cyclohexane (BDE = 99 kcal
      mol(-1)). CV experiments in THF solvent showed that 1 reacted with THF via rate
      determining attack at the THF C-H(D) bonds with a kinetic isotope effect of 10.2.
      Analysis of the kinetic and thermodynamic data provides new insights into the
      basis for the high reactivity of 1 and the possible involvement of species like 1
      in oxidation catalysis.

PMID- 25581556
TI  - Celiac is a social disease: family challenges and strategies.
AB  - Celiac disease is the most common autoimmune inherited disorder in the United
      States, affecting approximately 1% of the population. Little research exists on
      the impact of family processes on adherence to a gluten-free diet (GFD), the only
      treatment for celiac disease. The objective of this qualitative study was to
      examine the barriers that families with a celiac child face and the strategies
      they use to adhere to the recommended diet. In-depth interviews were conducted
      with 10 families with a child between the ages of 6 and 12 diagnosed with celiac
      disease. Grounded theory and narrative analysis were used to analyze interview
      transcripts. Social isolation and misunderstandings about celiac disease and the
      GFD emerged as the most significant barriers to diet adherence including the
      reproduction of traditional gender relations among parents. Diet adherence
      facilitators included various types of institutional and societal support and
      idiosyncratic family arrangements. Successful diet adherence strategies used by
      families included planning ahead and taking their own food to social functions.
      Family processes play a critical role in GFD adherence. Implications for health
      care clinicians working with families with a child with celiac disease are
      discussed.

PMID- 25581558
TI  - Major lessons learned from a nationally-based community-academic partnership:
      addressing sibling adjustment to childhood cancer.
AB  - Prolonged, intensive treatment protocols for childhood cancer disrupt family
      routines and daily functioning, with effects extending to all family members.
      Despite their unique needs, siblings of children with cancer receive limited
      attention from community organizations and researchers. Community-academic
      partnerships may foster research that effectively assesses and addresses
      siblings' unmet needs. In this article, "community" refers to siblings of
      children with cancer who participate in SuperSibs!, a national nonprofit
      organization for siblings of children with cancer. This article (a) describes a
      replicable model for successful community-academic partnerships: the Sibling
      Research Advisory Board (SRAB) and (b) articulates "lessons learned" from this
      partnership, including documenting the ability to recruit a representative sample
      through a community organization. Lessons emerged from an iterative process of
      discussion and revision that involved all SRAB members. This case study describes
      approaches to overcoming practical obstacles in community-partnered research
      planning and implementation. To meet the common goals of identifying and
      addressing unmet sibling needs, SRAB partners learned to establish a common
      language, identify each team member's unique expertise, and acknowledge
      differences in approach (e.g., methodology, pace of accomplishment) between
      research and community service. SRAB's ability to recruit a representative sample
      was achieved through close collaboration with SuperSibs! and implementation of
      active recruitment strategies to overcome barriers to research participation.
      Protection of community member privacy was emphasized alongside methodological
      rigor. Community-academic partnerships enable research with high-need, hard-to
      access populations. Proactively identifying and addressing common pitfalls of
      community-academic partnerships promotes community engagement and acceptability
      and facilitates high-quality research.

PMID- 25581557
TI  - Financial and employment impact of intellectual disability on families of
      children with autism.
AB  - Families of children with autism spectrum disorder (ASD) endure significant
      financial and employment burden because of their children's numerous needed
      services. The study objective is to describe additional impact on families of
      children with intellectual disability (ID) in addition to ASD. The study is a
      secondary data analysis of the 2009-2010 National Survey of Children with Special
      Health Care Needs. Children whose parents answered "yes" when asked whether their
      child had ASD or ID were classified as having ASD alone (unweighted n = 2,406),
      ID alone (unweighted n = 1,363), or both ASD/ID (unweighted n = 620). Bivariate
      and multivariate analyses compared study outcomes of family financial and
      caregiver burden using ASD as the reference group. All analyses were weighted
      using person-level estimates. Of children with ASD, 24% also had ID. More than
      half of caregivers of children with ASD/ID reported financial difficulty (52%)
      and having to stop work to care for their child (51%). Compared with ASD alone,
      caregivers of children with both ASD/ID were more likely to report financial
      difficulty (aOR 1.65, 95% CI 1.10-2.46), cutting work hours (aOR 1.43, 95% CI .98
      2.08), and stop working (aOR 2.32, 95% CI 1.57-3.43). No differences were found
      between caregivers of children with ASD only and ID only. We conclude that having
      ID in addition to ASD may be associated with greater negative impact on family
      financial and employment burden. Recognition of ID in addition to ASD is
      important to tailor the clinical approach and sufficiently support families.

PMID- 25581559
TI  - Presumed primary ocular lymphangiosarcoma with metastasis in a miniature horse.
AB  - A 7-year-old, 153.0-kg American Miniature mare presented for evaluation of
      keratoconjunctivitis of the right eye (OD). A superior palpebral conjunctival
      mass and stromal keratitis were diagnosed. The incisional biopsy diagnosis was a
      presumptive corneal hemangiosarcoma. Transpalpebral enucleation was performed,
      and histopathologic evaluation confirmed angiosarcoma of the conjunctiva, cornea,
      and extraocular muscles. The horse developed progressive epistaxis and orbital
      swelling following surgery. A systemic workup was performed 3 months after
      enucleation, revealing regrowth within the orbit and marked cranial cervical
      lymphomegaly, suggestive of metastasis. Humane euthanasia was performed, and
      necropsy confirmed a locally invasive periorbital tumor with metastasis to the
      submandibular tissue, submandibular lymph node, and thoracic inlet.
      Histopathologic evaluation of necropsy specimens revealed polygonal to spindle
      neoplastic cells lining neoplastic vascular channels lacking erythrocytes.
      Immunohistochemically, the neoplastic cells labeled strongly positive for PROX-1,
      vimentin, CD-31, VEGF, weakly positive for factor VIII-related antigen, and
      negative for collagen IV. Based on the clinical, histological, and
      immunohistochemical features of this tumor, a primary ocular lymphangiosarcoma
      with metastasis was diagnosed.

PMID- 25581561
TI  - Exciton dynamics reveal aggregates with intermolecular order at hidden interfaces
      in solution-cast organic semiconducting films.
AB  - Large-scale organic electronics manufacturing requires solution processing. For
      small-molecule organic semiconductors, solution processing results in crystalline
      domains with high charge mobility, but the interfaces between these domains
      impede charge transport, degrading device performance. Although understanding
      these interfaces is essential to improve device performance, their intermolecular
      and electronic structure is unknown: they are smaller than the diffraction limit,
      are hidden from surface probe techniques, and their nanoscale heterogeneity is
      not typically resolved using X-ray methods. Here we use transient absorption
      microscopy to isolate a unique signature of a hidden interface in a TIPS
      pentacene thin film, exposing its exciton dynamics and intermolecular structure.
      Surprisingly, instead of finding an abrupt grain boundary, we reveal that the
      interface can be composed of nanoscale crystallites interleaved by a web of
      interfaces that compound decreases in charge mobility. Our novel approach
      provides critical missing information on interface morphology necessary to
      correlate solution-processing methods to optimal device performance. 

PMID- 25581560
TI  - Identification of a direct GABAergic pallidocortical pathway in rodents.
AB  - Interaction between the basal ganglia and the cortex plays a critical role in a
      range of behaviors. Output from the basal ganglia to the cortex is thought to be
      relayed through the thalamus, but an intriguing alternative is that the basal
      ganglia may directly project to and communicate with the cortex. We explored an
      efferent projection from the globus pallidus externa (GPe), a key hub in the
      basal ganglia system, to the cortex of rats and mice. Anterograde and retrograde
      tracing revealed projections to the frontal premotor cortex, especially the deep
      projecting layers, originating from GPe neurons that receive axonal inputs from
      the dorsal striatum. Cre-dependent anterograde tracing in Vgat-ires-cre mice
      confirmed that the pallidocortical projection is GABAergic, and in vitro
      optogenetic stimulation in the cortex of these projections produced a fast
      inhibitory postsynaptic current in targeted cells that was abolished by
      bicuculline. The pallidocortical projections targeted GABAergic interneurons and,
      to a lesser extent, pyramidal neurons. This GABAergic pallidocortical pathway
      directly links the basal ganglia and cortex, and may play a key role in behavior
      and cognition in normal and disease states. 

PMID- 25581563
TI  - Predictors of Involvement and Warmth of Custodial Fathers in Israel: Comparison
      with Married and Noncustodial Divorced Fathers.
AB  - This study compared the levels and predictors of paternal warmth and involvement
      of 218 custodial fathers to 222 married fathers and 105 noncustodial (NC)
      divorced fathers in Israel. The examined predictors were fathers' perceptions of
      their own fathers; their own caregiving behaviors and parental self-efficacy; and
      child characteristics and coparental coordination. Results indicated that being a
      custodial father was associated with more involvement than being a married or NC
      divorced father. Regression analyses revealed that experience of care with own
      father predicted fathers' involvement, whereas own father control was related to
      lower paternal warmth. Lower avoidant caregiving and high paternal self-efficacy
      predicted both paternal involvement and warmth, whereas perceiving the child as
      more difficult predicted lower paternal warmth. Higher levels of coparental
      coordination were associated with more paternal involvement, whereas low
      coparental coordination was associated with less involvement, primarily among NC
      divorced fathers. These interactions highlight the distinct paternal behavior of
      custodial fathers. Unlike married and NC divorced fathers, they showed more
      warmth, regardless of their avoidant caregiving. Results are discussed in light
      of the different roles played by fathers in the three groups. 

PMID- 25581562
TI  - CASP10-BCL::Fold efficiently samples topologies of large proteins.
AB  - During CASP10 in summer 2012, we tested BCL::Fold for prediction of free modeling
      (FM) and template-based modeling (TBM) targets. BCL::Fold assembles the tertiary
      structure of a protein from predicted secondary structure elements (SSEs)
      omitting more flexible loop regions early on. This approach enables the sampling
      of conformational space for larger proteins with more complex topologies. In
      preparation of CASP11, we analyzed the quality of CASP10 models throughout the
      prediction pipeline to understand BCL::Fold's ability to sample the native
      topology, identify native-like models by scoring and/or clustering approaches,
      and our ability to add loop regions and side chains to initial SSE-only models.
      The standout observation is that BCL::Fold sampled topologies with a GDT_TS score
      > 33% for 12 of 18 and with a topology score > 0.8 for 11 of 18 test cases de
      novo. Despite the sampling success of BCL::Fold, significant challenges still
      exist in clustering and loop generation stages of the pipeline. The clustering
      approach employed for model selection often failed to identify the most native
      like assembly of SSEs for further refinement and submission. It was also observed
      that for some beta-strand proteins model refinement failed as beta-strands were
      not properly aligned to form hydrogen bonds removing otherwise accurate models
      from the pool. Further, BCL::Fold samples frequently non-natural topologies that
      require loop regions to pass through the center of the protein.

PMID- 25581564
TI  - Luminescent pincer platinum(II) complexes with emission quantum yields up to
      almost unity: photophysics, photoreductive C-C bond formation, and materials
      applications.
AB  - Luminescent pincer-type Pt(II)  complexes supported by C-deprotonated pi-extended
      tridentate R?C^N^N?R' ligands and pentafluorophenylacetylide ligands show
      emission quantum yields up to almost unity. Femtosecond time-resolved
      fluorescence measurements and time-dependent DFT calculations together reveal the
      dependence of excited-state structural distortions of [Pt(R?C^N^N?R')(C?C-C6 F5
      )] on the positional isomers of the tridentate ligand. Pt complexes [Pt(R
      C^N^N?R')(C?C-Ar)] are efficient photocatalysts for visible-light-induced
      reductive C?C bond formation. The [Pt(R-C^N^N?R')(C?C-C6 F5 )] complexes perform
      strongly as phosphorescent dopants for green- and red-emitting organic light
      emitting diodes (OLEDs) with external quantum efficiency values over 22.1 %.
      These complexes are also applied in two-photon cellular imaging when incorporated
      into mesoporous silica nanoparticles (MSNs). 

PMID- 25581566
TI  - Digital health technology and trauma: development of an app to standardize care.
AB  - BACKGROUND: Standardized practice results in less variation, therefore reducing
      errors and improving outcome. Optimal trauma care is achieved through
      standardization, as is evidenced by the widespread adoption of the Advanced
      Trauma Life Support approach. The challenge for an individual institution is how
      does one educate and promulgate these standardized processes widely and
      efficiently? In today's world, digital health technology must be considered in
      the process. AIM: The aim of this study was to describe the process of developing
      an app, which includes standardized trauma algorithms. The objective of the app
      was to allow easy, real-time access to trauma algorithms, and therefore reduce
      omissions/errors. METHOD: A set of trauma algorithms, relevant to the local
      setting, was derived from the best available evidence. After obtaining grant
      funding, a collaborative endeavour was undertaken with an external specialist app
      developing company. RESULTS: The process required 6 months to translate the
      existing trauma algorithms into an app. The app contains 32 separate trauma
      algorithms, formatted as a single-page flow diagram. It utilizes specific
      smartphone features such as 'pinch to zoom', jump-words and pop-ups to allow
      rapid access to the desired information. CONCLUSION: Improvements in trauma care
      outcomes result from reducing variation. By incorporating digital health
      technology, a trauma app has been developed, allowing easy and intuitive access
      to evidenced-based algorithms.

PMID- 25581565
TI  - Potential overtreatment of diabetes mellitus in older adults with tight glycemic
      control.
AB  - IMPORTANCE: In older adults with multiple serious comorbidities and functional
      limitations, the harms of intensive glycemic control likely exceed the benefits.
      OBJECTIVES: To examine glycemic control levels among older adults with diabetes
      mellitus by health status and to estimate the prevalence of potential
      overtreatment of diabetes. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional
      analysis of the data on 1288 older adults (>=65 years) with diabetes from the
      National Health and Nutrition Examination Survey (NHANES) from 2001 through 2010
      who had a hemoglobin A1c (HbA1c) measurement. All analyses incorporated complex
      survey design to produce nationally representative estimates. EXPOSURES: Health
      status categories: very complex/poor, based on difficulty with 2 or more
      activities of daily living or dialysis dependence; complex/intermediate, based on
      difficulty with 2 or more instrumental activities of daily living or presence of
      3 or more chronic conditions; and relatively healthy if none of these were
      present. MAIN OUTCOMES AND MEASURES: Tight glycemic control (HbA1c level, <7%)
      and use of diabetes medications likely to result in hypoglycemia (insulin or
      sulfonylureas). RESULTS: Of 1288 older adults with diabetes, 50.7% (95% CI, 46.6%
      54.8%), representing 3.1 million (95% CI, 2.7-3.5), were relatively healthy,
      28.1% (95% CI, 24.8%-31.5%), representing 1.7 million (95% CI, 1.4-2.0), had
      complex/intermediate health, and 21.2% (95% CI, 18.3%-24.4%), representing 1.3
      million (95% CI, 1.1-1.5), had very complex/poor health. Overall, 61.5% (95% CI,
      57.5%-65.3%), representing 3.8 million (95% CI, 3.4-4.2), had an HbA1c level of
      less than 7%; this proportion did not differ across health status categories
      (62.8% [95% CI, 56.9%-68.3%]) were relatively healthy, 63.0% (95% CI, 57.0%
      68.6%) had complex/intermediate health, and 56.4% (95% CI, 49.7%-62.9%) had very
      complex/poor health (P = .26). Of the older adults with an HbA1c level of less
      than 7%, 54.9% (95% CI, 50.4%-59.3%) were treated with either insulin or
      sulfonylureas; this proportion was similar across health status categories (50.8%
      [95% CI, 45.1%-56.5%] were relatively healthy, 58.7% [95% CI, 49.4%-67.5%] had
      complex/intermediate health, and 60.0% [95% CI, 51.4%-68.1%] had very
      complex/poor health; P = .14). During the 10 study years, there were no
      significant changes in the proportion of older adults with an HbA1c level of less
      than 7% (P = .34), the proportion with an HbA1c level of less than 7% who had
      complex/intermediate or very complex/poor health (P = .27), or the proportion
      with an HbA1c level of less than 7% who were treated with insulin or
      sulfonylureas despite having complex/intermediate or very complex/poor health (P
      = .65). CONCLUSIONS AND RELEVANCE: Although the harms of intensive treatment
      likely exceed the benefits for older patients with complex/intermediate or very
      complex/poor health status, most of these adults reached tight glycemic targets
      between 2001 and 2010. Most of them were treated with insulin or sulfonylureas,
      which may lead to severe hypoglycemia. Our findings suggest that a substantial
      proportion of older adults with diabetes were potentially overtreated.

PMID- 25581567
TI  - Codelivery of antitumor drug and gene by a pH-sensitive charge-conversion system.
AB  - In the present study, a gene and drug codelivery system was developed by
      electrostatic binding of polyethylenimine-poly(l-lysine)-poly(l-glutamic acid)
      (PELG), polyethylenimine (PEI), cis-aconityl-doxorubicin (CAD), and DNA. Zeta
      potential and drug release analysis confirmed the pH-responsive charge conversion
      and acid-sensitive drug release functional properties of the PELG/PEI/(DNA+CAD)
      system. Gel retardation assay and transfection experiment showed the codelivery
      system had effective DNA binding ability and good transfection efficiency on
      HepG2 cells. The therapeutic gene p53 was further employed to study its
      combinational effects with CAD. Cytotoxicity assay showed the half inhibitory
      concentration (IC50) of the PELG/PEI/(p53+CAD) codelivery system was lower than
      that of the gene or the drug delivery system. Confocal laser scanning microscopy
      (CLSM) showed that the drug and gene could be delivered into the cells
      simultaneously. A significant increase of p53 gene expression was achieved after
      HepG2 cells treated by PELG/PEI/(p53+CAD) codelivery system. The apoptosis
      experiment indicated clearly that the codelivery system could lead an effective
      apoptosis on tumor cells, which was beneficial for the treatment of cancer. The
      biodistribution and tumor accumulation of the codelivery system was explored via
      in vivo imaging in subcutaneous xenograft and in situ tumor models. The tumor and
      some major organs were excised and imaged, and the results showed that the
      codelivery system can accumulate efficiently in tumor for both tumor models. It
      can be suggested from the above results that the PELG/PEI/(DNA+CAD) codelivery
      system will have great potential applications in cancer therapy. 

PMID- 25581568
TI  - Soil bacterial communities are shaped by temporal and environmental filtering:
      evidence from a long-term chronosequence.
AB  - Soil microbial communities are abundant, hyper-diverse and mediate global
      biogeochemical cycles, but we do not yet understand the processes mediating their
      assembly. Current hypothetical frameworks suggest temporal (e.g. dispersal
      limitation) and environmental (e.g. soil pH) filters shape microbial community
      composition; however, there is limited empirical evidence supporting this
      framework in the hyper-diverse soil environment, particularly at large spatial
      (i.e. regional to continental) and temporal (i.e. 100 to 1000 years) scales.
      Here, we present evidence from a long-term chronosequence (4000 years) that
      temporal and environmental filters do indeed shape soil bacterial community
      composition. Furthermore, nearly 20 years of environmental monitoring allowed us
      to control for potentially confounding environmental variation. Soil bacterial
      communities were phylogenetically distinct across the chronosequence. We
      determined that temporal and environmental factors accounted for significant
      portions of bacterial phylogenetic structure using distance-based linear models.
      Environmental factors together accounted for the majority of phylogenetic
      structure, namely, soil temperature (19%), pH (17%) and litter carbon:nitrogen
      (C:N; 17%). However, of all individual factors, time since deglaciation accounted
      for the greatest proportion of bacterial phylogenetic structure (20%). Taken
      together, our results provide empirical evidence that temporal and environmental
      filters act together to structure soil bacterial communities across large spatial
      and long-term temporal scales.

PMID- 25581569
TI  - Low-frequency electrical stimulation induces the proliferation and
      differentiation of peripheral blood stem cells into Schwann cells.
AB  - BACKGROUND: Functional recovery after peripheral nerve injury remains a tough
      problem at present. Specifically, a type of glial cell exists in peripheral
      nerves that promotes axonal growth and myelin formation and secretes various
      active substances, such as neurotrophic factors, extracellular matrix and
      adherence factors. These substances have important significance for the survival,
      growth and regeneration of nerve fibers. Numerous recent studies have shown that
      electrical stimulation can increase the number of myelinated nerve fibers.
      However, whether electrical stimulation acts on neurons or Schwann cells has not
      been verified in vivo. This study investigates low-frequency electrical
      stimulation-induced proliferation and differentiation of peripheral blood stem
      cells into Schwann cells and explores possible mechanisms. METHODS: Peripheral
      blood stem cells from Sprague-Dawley rats were primarily cultured. Cells in
      passage 3 were divided into 4 groups: a low-frequency electrical stimulation
      group (20 Hz, 100 MUs, 3 V), a low-frequency electrical stimulation+PD98059
      (blocking the extracellular signal-regulated kinase [ERK] signaling pathway)
      group, a PD98059 group and a control group (no treatment). After induction, the
      cells were characterized. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazoliumbromide assay was employed to measure the absorbance values at 570 nm
      in the 4 groups. A Western blot assay was used to detect the expression of cyclin
      D1 and cyclin-dependent kinase 4 (CDK4) in each group. RESULTS: No significant
      difference in cell viability was detected before induction. Peripheral blood stem
      cells from the 4 groups differentiated into Schwann cells. Phosphorylated ERK
      1/2, cyclin D1 and CDK4 protein levels were highest in the low-frequency
      electrical stimulation group and lowest in the ERK blockage group. Phosphorylated
      ERK 1/2, cyclin D1 and CDK4 protein levels in the low-frequency electrical
      stimulation+ERK blockage group were lower than those in the low-frequency
      electrical stimulation group but higher than those in the ERK blockage group.
      CONCLUSIONS: Low-frequency electrical stimulation contributed to the
      proliferation of peripheral blood stem cells cultured in vitro and induced
      differentiation into Schwann cells. The ERK signaling pathway underlies cell
      proliferation and differentiation.

PMID- 25581570
TI  - Methylglyoxal and advanced glycation end-products promote cytokines expression in
      peritoneal mesothelial cells via MAPK signaling.
AB  - BACKGROUND: Peritoneal dialysis fluid degrades glucose into glucose degradation
      products that impair peritoneal mesothelial cell functions. These compounds are
      known to interfere with many cellular functions and to promote the formation of
      advanced glycation end products (AGEs). This study aimed to investigate the
      biological effects and the underlying mechanism of glucose degradation products
      and AGEs on mesothelial cells. METHODS: Cell proliferation was determined using
      [3H]-thymidine incorporation assay. Real-time polymerase chain reaction and
      enzyme linked immunosorbent assay (ELISA) were used to determine the mRNA and
      protein expression of cytokines. Reactive oxygen species production in
      mesothelial cells was determined by flow cytometry. Western blot was used to
      measure the protein expression of p38 MAPK. RESULTS: Methylglyoxal (MGO) and AGE
      human serum albumin (AGE-HSA) inhibited human peritoneal mesothelial cells
      proliferation in a dose- and time-dependent manner. The mRNA and protein
      expression of cytokines including vascular endothelial growth factor (VEGF) and
      monocyte chemotactic protein-1 (MCP-1) was significantly increased after
      treatment with MGO and AGE-HSA. Also, the antioxidant N-acetylcysteine (NAC)
      inhibited MGO- or AGE-HSA-induced reactive oxygen species generation. Western
      blot showed that MGO and AGE increased the phosphorylation levels of p38 MAPK,
      which was significantly attenuated after treatment of NAC or p38 MAPK inhibitor
      SB203580. Furthermore, AGE- or MGO-induced increased expression of VEGF and MCP-1
      was significantly reduced in the presence of NAC or SB203580. CONCLUSIONS:
      Together, this study suggested that AGE or MGO promoted VEGF and MCP-1 expression
      through activation of p38 MAPK signaling.

PMID- 25581571
TI  - The role of SDF-1 in homing of human adipose-derived stem cells.
AB  - One of the putative pathophysiological mechanisms of chronic wounds is a
      disturbed homing of stem cells. In this project, the stromal cell-derived factor
      1 (SDF-1)/C-X-C chemokine receptor (CXCR) 4 and SDF-1/CXCR7 pathway were focused
      in human adipose-derived stem cells (ASCs). ASCs were incubated with acute (AWF)
      or chronic wound fluid (CWF) to analyze their effects by quantitative real-time
      polymerase chain reaction (SDF-1, CXCR4, CXCR7, TIMP3), enzyme-linked
      immunosorbent assay (SDF-1 in WFs and supernatant), and transwell migration assay
      with/without antagonization. Whereas SDF-1 amounted 73.5 pg/mL in AWF, it could
      not be detected in CWF. Incubation with AWF led to a significant enhancement
      (129.7 pg/mL vs. 95.5 pg/mL), whereas CWF resulted in a significant reduction (30
      pg/mL vs. 95.5 pg/mL) of SDF-1 in ASC supernatant. The SDF-1 receptor CXCR7 was
      detected on ASCs. AWF but not CWF significantly induced ASC migration, which was
      inhibited by CXCR4 and CXCR7 antagonists. Expressions of SDF-1, CXCR4, and CXCR7
      were significantly stimulated by AWF while TIMP3 expression was reduced. In
      conclusion, an uncontrolled inflammation in the chronic wound environment,
      indicated by a reduced SDF-1 expression, resulted in a decreased ASC migration. A
      disturbed SDF-1/CXCR4 as well as SDF-1/CXCR7 pathway seems to play an important
      role in the impaired healing of chronic wounds. 

PMID- 25581572
TI  - Linear mixed model approach to network meta-analysis for continuous outcomes in
      periodontal research.
AB  - AIM: Analysing continuous outcomes for network meta-analysis by means of linear
      mixed models is a great challenge, as it requires statistical software packages
      to specify special patterns of model error variance and covariance structure.
      This article demonstrates a non-Bayesian approach to network meta-analysis for
      continuous outcomes in periodontal research with a special focus on the
      adjustment of data dependency. DATA: Seventeen studies on guided tissue
      regeneration were used to illustrate how the proposed linear mixed models for
      network meta-analysis of continuous outcomes. METHODS & RESULTS: Arm-based
      network meta-analysis use treatment arms from each study as the unit of analysis;
      when patients are randomly assigned to each arm, data are deemed independent and
      therefore no adjustment is required for multi-arm trials. Trial-based network
      meta-analysis use treatment contrasts as the unit of analysis, and therefore
      treatment contrasts within a multi-arm trial are not independent. This data
      dependency occurs also in split-mouth studies, and adjustments for data
      dependency are therefore required. CONCLUSIONS: Arm-based analysis is the
      preferred approach to network meta-analysis, when all included studies use the
      parallel group design and some compare more than two treatment arms. When
      included studies used designs that yield dependent data, the trial-based analysis
      is the preferred approach.

PMID- 25581573
TI  - TM6SF2 E167K variant is associated with severe steatosis in chronic hepatitis C,
      regardless of PNPLA3 polymorphism.
AB  - BACKGROUND & AIMS: A common non-synonymous polymorphism, E167K, in transmembrane
      six superfamily member 2 (TM6SF2) gene has been recently associated with an
      increased hepatic triglyceride content, dyslipidemia and liver fibrosis in NAFLD
      patients. We investigated possible associations between the TM6SF2 variants and
      liver lesions in chronic hepatitis C. PATIENTS AND METHODS: 148 consecutive
      patients with biopsy proven anti-HCV/HCV-RNA-positive chronic hepatitis, naive
      for antiviral therapy, were genotyped for TM6SF2 E167K and PNPLA3 I148M variants.
      RESULTS: The score of liver steatosis was higher in the 18 patients with TM6SF2
      E167K variant (mean 1.9 +/- 1.3) than in the 130 homozygotes for TM6SF2 167E
      allele (1.1 +/- 1.1, P = 0.02), and the prevalence of a steatosis score >= 3 was
      33.3% vs. 12.3% respectively (P = 0.02). No difference in necroinflammatory or
      fibrosis scores was found between the two groups. A general linear model
      identified as independent predictors of steatosis TM6SF2 E167K and PNPLA3 M148M
      variants and waist circumference (P = 0.0376, P = 0.0069 and P = 0.0273
      respectively). CONCLUSIONS: This is the first demonstration that TM6SF2 E167K
      variant is an independent predictor of liver steatosis in chronic hepatitis C.

PMID- 25581575
TI  - Kinetic resolution of racemic amino alcohols through intermolecular acetalization
      catalyzed by a chiral Bronsted acid.
AB  - The kinetic resolution of racemic secondary alcohols is a fundamental method for
      obtaining enantiomerically enriched alcohols. Compared to esterification, which
      is a well-established method for this purpose, kinetic resolution through
      enantioselective intermolecular acetalization has not been reported to date
      despite the fact that the formation of acetals is widely adopted to protect
      hydroxy groups. By taking advantage of the thermodynamics of acetalization by the
      addition of alcohols to enol ethers, a highly efficient kinetic resolution of
      racemic amino alcohols was achieved for the first time and in a practical manner
      using a chiral phosphoric acid catalyst. 

PMID- 25581574
TI  - Pharmacological activation of Nrf2 pathway improves pancreatic islet isolation
      and transplantation.
AB  - Oxidative stress is a major cause of islet damage and loss during the islet
      isolation process. The Nrf2 pathway plays a critical role in protecting the cells
      against oxidative stress. The aim of this study was to investigate the effect of
      an Nrf2 activator (dh404) on islet isolation and transplantation in a rodent
      model. Islet isolation was conducted using Nrf2-deficient and wild-type mice and
      vehicle-treated and Nrf2 activator (dh404)-treated rats. Islet yield, viability,
      and Nrf2 pathway activity were determined. An in vivo islet potency test was
      done. Islet yield and viability in Nrf2-deficient mice was significantly lower
      compared to wild-type (p < 0.05) mice. Furthermore, administration of dh404 to
      normal Sprague-Dawley rats enhanced nuclear translocation of Nrf2 and elevated HO
      1 expression in the pancreas. Islet yield and viability in dh404-treated rats was
      significantly higher compared to the vehicle-treated group (p < 0.05). The
      diabetes cure rate in nude mice with chemically induced diabetes was
      significantly greater in those transplanted with islets from the dh404-treated
      group (6/9) than vehicle-treated rats (2/9, p < 0.05). The Nrf2 pathway plays a
      significant role in protecting islets against stress caused by the isolation
      process. Pharmacological activation of the Nrf2 pathway significantly increased
      HO-1 expression, improved islet yield, viability, and function after
      transplantation. 

PMID- 25581576
TI  - Clinical phenotype of X-linked myotubular myopathy in Labrador Retriever puppies.
AB  - BACKGROUND: Seven male Labrador Retriever puppies from 3 different litters, born
      to clinically normal dams and sires, were evaluated for progressive weakness and
      muscle atrophy. Muscle biopsies identified a congenital myopathy with pathologic
      features consistent with myotubular myopathy. Further investigations identified a
      pathogenic mutation in the myotubularin gene, confirming that these puppies had X
      linked myotubular myopathy (XLMTM). OBJECTIVE: To review the clinical phenotype,
      electrodiagnostic and laboratory features of XLMTM in this cohort of Labrador
      Retrievers. RESULTS: Male puppies with XLMTM were small and thin compared with
      their normal littermates. Generalized weakness and muscle atrophy were present by
      7 weeks of age in some puppies and evident to most owners by 14 weeks of age.
      Affected puppies stood with an arched spine and low head carriage, and walked
      with a short, choppy stride. Muscle atrophy was severe and progressive. Patellar
      reflexes were absent. Laryngeal and esophageal dysfunction, and weakness of the
      masticatory muscles occurred in puppies surviving beyond 4 months of age. Serum
      creatine kinase activity was normal or only mildly increased. EMG findings were
      nonspecific and included positive sharp waves and fibrillation potentials.
      Clinical signs progressed rapidly, with most affected puppies unable to walk
      within 3-4 weeks after clinical signs were first noticed. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Although initial clinical signs of XLMTM are similar to the
      phenotypically milder centronuclear myopathy in Labrador Retrievers, XLMTM is a
      rapidly progressive and fatal myopathy. Clinicians should be aware of these 2
      distinct myopathies with similar clinical presentations in the Labrador retriever
      breed.

PMID- 25581577
TI  - The dependability of electrophysiological measurements of performance monitoring
      in a clinical sample: A generalizability and decision analysis of the ERN and Pe.
AB  - Psychometric studies of the ERN, CRN, Pe, and Pc ERPs are increasing. Coherent
      integration of these results is difficult with classical test theory because the
      definition of error depends on the measure of reliability. This study used
      generalizability theory, which extends the ideas of classical test theory, as a
      framework for evaluating the influence of psychopathology and number of trials on
      dependability of measurement. Participants included 34 people meeting criteria
      for major depression, 29 meeting criteria for an anxiety disorder, and 319
      controls. For all ERPs, within-person variance was larger than between-person
      variance across groups, indicating many trials are needed for adequate
      dependability (at least 13). Slightly fewer trials were needed to achieve
      adequate dependability in the control group than the pathology groups. Regions of
      interest had higher dependability than single sensors. 

PMID- 25581578
TI  - The role of vegetation-microclimate feedback in promoting shrub encroachment in
      the northern Chihuahuan desert.
AB  - Many arid and semi-arid landscapes around the world are affected by a shift from
      grassland to shrubland vegetation, presumably induced by climate warming,
      increasing atmospheric CO2 concentrations, and/or changing land use. This major
      change in vegetation cover is likely sustained by positive feedbacks with the
      physical environment. Recent research has focused on a feedback with
      microclimate, whereby cold intolerant shrubs increase the minimum nocturnal
      temperatures in their surroundings. Despite the rich literature on the impact of
      land cover change on local climate conditions, changes in microclimate resulting
      from shrub expansion into desert grasslands have remained poorly investigated. It
      is unclear to what extent such a feedback can affect the maximum extent of shrub
      expansion and the configuration of a stable encroachment front. Here, we focus on
      the case of the northern Chihuahuan desert, where creosotebush (Larrea
      tridentata) has been replacing grasslands over the past 100-150 years. We use a
      process-based coupled atmosphere-vegetation model to investigate the role of this
      feedback in sustaining shrub encroachment in the region. Simulations indicate
      that the feedback allows juvenile shrubs to establish in the grassland during
      average years and, once established, reduce their vulnerability to freeze-induced
      mortality by creating a warmer microclimate. Such a feedback is crucial in
      extreme cold winters as it may reduce shrub mortality. We identify the existence
      of a critical zone in the surroundings of the encroachment front, in which
      vegetation dynamics are bistable: in this zone, vegetation can be stable both as
      grassland and as shrubland. The existence of these alternative stable states
      explains why in most cases the shift from grass to shrub cover is found to be
      abrupt and often difficult to revert. 

PMID- 25581580
TI  - Writing for publication in the BJD: tips for fledglings.

PMID- 25581581
TI  - Propranolol for infantile haemangiomas: certain chances, potential risks.

PMID- 25581579
TI  - Heterozygous triplication of upstream regulatory sequences leads to dysregulation
      of matrix metalloproteinase 19 in patients with cavitary optic disc anomaly.
AB  - Patients with a congenital optic nerve disease, cavitary optic disc anomaly
      (CODA), are born with profound excavation of the optic nerve resembling glaucoma.
      We previously mapped the gene that causes autosomal-dominant CODA in a large
      pedigree to a chromosome 12q locus. Using comparative genomic hybridization and
      quantitative PCR analysis of this pedigree, we report identifying a 6-Kbp
      heterozygous triplication upstream of the matrix metalloproteinase 19 (MMP19)
      gene, present in all 17 affected family members and no normal members. Moreover,
      the triplication was not detected in 78 control subjects or in the Database of
      Genomic Variants. We further detected the same 6-Kbp triplication in one of 24
      unrelated CODA patients and in none of 172 glaucoma patients. Analysis with a
      Luciferase assay showed that the 6-Kbp sequence has transcription enhancer
      activity. A 773-bp fragment of the 6-Kbp DNA segment increased downstream gene
      expression eightfold, suggesting that triplication of this sequence may lead to
      dysregulation of the downstream gene, MMP19, in CODA patients. Lastly,
      immunohistochemical analysis of human donor eyes revealed strong expression of
      MMP19 in optic nerve head. These data strongly suggest that triplication of an
      enhancer may lead to overexpression of MMP19 in the optic nerve that causes CODA.

PMID- 25581582
TI  - Risk of mortality in hydroa vacciniforme and hypersensitivity to mosquito bites.

PMID- 25581583
TI  - Pemphigoid gestationis.

PMID- 25581584
TI  - Photodynamic therapy versus topical imiquimod versus topical fluorouracil for
      treatment of superficial basal-cell carcinoma: a single blind, non-inferiority,
      randomised controlled trial: a critical appraisal.
AB  - AIM: Arits et al. aimed to assess whether the effectiveness of imiquimod and
      fluorouracil is not inferior to methyl aminolaevulinic acid (MAL) photodynamic
      therapy (PDT) in patients with superficial basal cell carcinoma. SETTING AND
      DESIGN: This single-blind, noninferiority, randomized controlled trial was
      conducted at one coordinating academic hospital and six peripheral dermatological
      departments in the Netherlands between March 2008 and August 2010. STUDY
      EXPOSURE: Patients with a superficial basal cell carcinoma were randomly assigned
      to be treated with PDT (two treatments); or imiquimod 5% cream, once daily five
      times a week for 6 weeks; or fluorouracil 5% cream twice daily for 4 weeks.
      Follow-up visits were planned after 3 months and 1 year. OUTCOMES: The primary
      outcome was defined as the probability that a patient was free of tumour
      reoccurrence at both 3 and 12 months' follow-up. Secondary outcomes were
      aesthetic outcome of the treated area, compliance and adverse reactions. RESULTS:
      In total 911 patients were assessed for eligibility, of whom 601 were randomized:
      202 to receive MAL-PDT, 198 to receive imiquimod cream and 201 to receive
      fluorouracil cream. The proportions (95% confidence intervals) of patients tumour
      free at both 3 and 12 months were 72.8% (66.8-79.4) for MAL-PDT, 83.4% (78.2
      88.9) for imiquimod cream and 80.1% (74.7-85.9) for fluorouracil cream. For
      patients treated with MAL-PDT, moderate-to-severe pain and burning sensation were
      reported most often during the treatment itself. For the creams, moderate-to
      severe local swelling, erosion, crust formation and itching of the skin were
      mentioned most often. CONCLUSIONS: Arits et al. conclude that topical
      fluorouracil was noninferior and imiquimod was superior to MAL-PDT for treatment
      of superficial basal cell carcinoma. Imiquimod cream is suggested as the
      preferred treatment.

PMID- 25581585
TI  - Response to 'Photodynamic therapy versus topical imiquimod versus topical
      fluorouracil for treatment of superficial basal-cell carcinoma: a single blind,
      non-inferiority, randomised controlled trial: a critical appraisal'.

PMID- 25581586
TI  - Commentary on 'Photodynamic therapy versus topical imiquimod versus topical
      fluorouracil for treatment of superficial basal-cell carcinoma: a single blind,
      non-inferiority, randomised controlled trial'.

PMID- 25581590
TI  - Vibrational signatures to discriminate liver steatosis grades.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a frequent lesion associated with
      obesity, diabetes and the metabolic syndrome. The hallmark feature of fatty liver
      disease is steatosis, which is the intra-cellular accumulation of lipids
      resulting in the formation of vesicles in hepatocytes. Steatosis is a precursor
      of steatohepatitis, a condition that may progress to hepatic fibrosis, cirrhosis
      and primary liver cancer. We addressed the potential of Fourier transform
      infrared (FTIR) microspectroscopy for grading steatosis on frozen tissue
      sections. The use of the bright infrared source emitted by synchrotron radiation
      (SR) allowed the investigation of the biochemical composition at the cellular
      level. The variance in the huge number of spectra acquired was addressed by
      principal component analysis (PCA). The study demonstrated that the progression
      of steatosis corresponds not only to the accumulation of lipids but also to
      dramatic changes in the qualitative composition of the tissue. Indeed, a lower
      grade of steatosis showed a decrease in glycogen content and a concomitant
      increase in lipids in comparison with normal liver. Intermediate steatosis
      exhibited an increase in glycogen and major changes in lipids, with a significant
      contribution of esterified fatty acids with elongated carbon chains and
      unsaturated lipids, and these features were more pronounced in a high grade of
      steatosis. Furthermore, the approach allows a systematic discrimination of
      morphological features, leading to a separate investigation of steatotic vesicles
      and the non-steatotic counterpart of the tissue. This highlighted the fact that
      dramatic biochemical changes occur in the non-steatotic part of the tissue also
      despite its normal histological aspect, suggesting that the whole tissue reflects
      the grade of steatosis. 

PMID- 25581591
TI  - 'It was like he was in the room with us': patients' and carers' perspectives of
      telemedicine in acute stroke.
AB  - BACKGROUND: Telemedicine can facilitate delivery of thrombolysis in acute stroke.
      The aim of this qualitative study was to explore patients' and carers' views of
      their experiences of using a stroke telemedicine system in order to contribute to
      the development of reliable and acceptable telemedicine systems and training for
      health-care staff. METHOD: We recruited patients who had, and carers who were
      present at, recent telemedicine consultations for acute stroke in three hospitals
      in NW England. Semi-structured interviews were conducted using an interview guide
      based on normalization process theory (NPT). Thematic analysis was undertaken.
      RESULTS: We conducted 24 interviews with 29 participants (16 patients; 13
      carers). Eleven interviews pertained to 'live' telemedicine assessments (at the
      time of admission); nine had mock-up telemedicine assessments (within 48 h of
      admission); four had both assessments. Using the NPT domains as a framework for
      analysis, factors relating to coherence (sense making) included people's
      knowledge and understanding of telemedicine. Cognitive participation (relational
      work) included interaction between staff and with patients and carers. Issues
      relating to collective action (operational work) included information exchange
      and support, and technical matters. Findings relating to reflexive monitoring
      (appraisal) included positive and negative impressions of the telemedicine
      process, and emotional reactions. CONCLUSION: Although telemedicine was well
      accepted by many participants, its use added an additional layer of complexity to
      the acute stroke consultation. The 'remote' nature of the consultation posed
      challenges for some patients. These issues may be ameliorated by clear
      information for patients and carers, staff interpersonal skills, and teamworking.

PMID- 25581592
TI  - Rapid residue analysis of oxathiapiprolin and its metabolites in typical Chinese
      soil, water, and sediments by a modified quick, easy, cheap, effective, rugged,
      and safe method with ultra high performance liquid chromatography and tandem mass
      spectrometry.
AB  - A sensitive and effective method for the simultaneous determination of residues
      from a new fungicide, oxathiapiprolin, and its metabolites (IN-E8S72 and IN
      WR791) in soil, water, and sediment, was developed using ultra high performance
      liquid chromatography with tandem mass spectrometry. Three compounds were
      extracted from water, soil, and sediment by using acetonitrile and different
      proportions of formic acid aqueous solution (1% v/v for water; 2% v/v for soil;
      and sediment), and were cleaned with octadecylsilane. The target compounds were
      determined within 5 min using an electrospray ionization source in the positive
      mode for oxathiapiprolin and in the negative mode for the two metabolites. The
      limits of quantification for all the three compounds were 0.1 MUg/kg in water and
      1 MUg/kg in soil and sediment. Recovery studies were performed using three spiked
      levels (0.1, 1, and 10 MUg/kg for water; 1, 10, and 50 MUg/kg for soil and
      sediment). The overall average recoveries ranged from 64.8 to 112.7% with all
      intra- and interday relative standard deviation values below 19.4 and 19.1%,
      respectively. The method validation confirmed that the proposed method was
      convenient and reliable for determining residual oxathiapiprolin and its
      metabolites in soil, water, and sediments.

PMID- 25581593
TI  - Use of a seagrass residency index to apportion commercial fishery landing values
      and recreation fisheries expenditure to seagrass habitat service.
AB  - Where they dominate coastlines, seagrass beds are thought to have a fundamental
      role in maintaining populations of exploited species. Thus, Mediterranean
      seagrass beds are afforded protection, yet no attempt to determine the
      contribution of these areas to both commercial fisheries landings and
      recreational fisheries expenditure has been made. There is evidence that seagrass
      extent continues to decline, but there is little understanding of the potential
      impacts of this decline. We used a seagrass residency index, that was trait and
      evidence based, to estimate the proportion of Mediterranean commercial fishery
      landings values and recreation fisheries total expenditure that can be attributed
      to seagrass during different life stages. The index was calculated as a weighted
      sum of the averages of the estimated residence time in seagrass (compared with
      other habitats) at each life stage of the fishery species found in seagrass.
      Seagrass-associated species were estimated to contribute 30%-40% to the value of
      commercial fisheries landings and approximately 29% to recreational fisheries
      expenditure. These species predominantly rely on seagrass to survive juvenile
      stages. Seagrass beds had an estimated direct annual contribution during
      residency of ?58-91 million (4% of commercial landing values) and ?112 million
      (6% of recreation expenditure) to commercial and recreational fisheries,
      respectively, despite covering <2% of the area. These results suggest there is a
      clear cost of seagrass degradation associated with ineffective management of
      seagrass beds and that policy to manage both fisheries and seagrass beds should
      take into account the socioeconomic implications of seagrass loss to recreational
      and commercial fisheries.

PMID- 25581594
TI  - Renal sinus exposure as an independent factor predicting asymptomatic unruptured
      pseudoaneurysm formation detected in the early postoperative period after
      minimally invasive partial nephrectomy.
AB  - OBJECTIVES: To investigate the incidence of asymptomatic unruptured renal artery
      pseudoaneurysm detected by 3-D computed tomography arteriography in the early
      period after minimally invasive partial nephrectomy, including laparoscopic and
      robotic partial nephrectomy. METHODS: From February 2012 to November 2013, 101
      patients underwent minimally invasive partial nephrectomy for renal masses.
      Computed tomography arteriography was carried out 3-4 days after surgery;
      radiologists diagnosed renal artery pseudoaneurysm in a blinded manner. Factors
      influencing the occurrence of renal artery pseudoaneurysm were analyzed with the
      logistic regression model. RESULTS: The incidence of renal artery pseudoaneurysm
      was unexpectedly high at 21.7% when detected by computed tomography arteriography
      during the early period after minimally invasive partial nephrectomy. The renal
      artery pseudoaneurysm group showed a significantly larger tumor size (P = 0.02),
      significantly higher N component score (P = 0.01) and higher incidence of renal
      sinus exposure or opening of the collecting system (P < 0.01) compared with the
      no renal artery pseudoaneurysm group. Although these aforementioned factors were
      found to be significant by univariate analysis, multivariate analysis showed that
      renal sinus exposure was the only significant independent predictive factor for
      occurrence of renal artery pseudoaneurysm. Tumor-related factors, such as the N
      component of the nephrometry scoring system or tumor size, did not show an
      independent influence on the occurrence of renal artery pseudoaneurysm.
      CONCLUSIONS: The present study shows an unexpectedly high incidence of
      asymptomatic unruptured renal artery pseudoaneurysm detected by computed
      tomography arteriography in the early period after minimally invasive partial
      nephrectomy. Renal sinus exposure is an independent significant factor predicting
      the occurrence of renal artery pseudoaneurysm. Avoidance of deep excision into
      the renal sinus could reduce the risk of renal artery pseudoaneurysm.

PMID- 25581595
TI  - Impact of a Suicide-Specific Intervention within Inpatient Psychiatric Care: The
      Collaborative Assessment and Management of Suicidality.
AB  - A growing body of literature indicates that suicidal patients differ from other
      psychiatric patients with respect to specific psychological vulnerabilities and
      that suicide-specific interventions may offer benefits beyond conventional care.
      This naturalistic controlled-comparison trial (n = 52) examined outcomes of
      intensive psychiatric hospital treatment (mean length of stay 58.8 days),
      comparing suicidal patients who received individual therapy from clinicians
      utilizing the Collaborative Assessment and Management of Suicidality (CAMS) to
      patients whose individual therapists did not utilize CAMS. Propensity score
      matching was used to control for potential confounds, including age, sex,
      treatment unit, and severity of depression and suicidality. Results showed that
      both groups improved significantly over the course of hospitalization; however,
      the group receiving CAMS showed significantly greater improvement on measures
      specific to suicidal ideation and suicidal cognition. Results are discussed in
      terms of the potential advantages of treating suicide risk with a suicide
      specific intervention to make inpatient psychiatric treatment more effective in
      reducing risk for future suicidal crises.

PMID- 25581596
TI  - Postoperative simultaneous integrated boost-intensity modulated radiation therapy
      for patients with locoregionally advanced papillary thyroid carcinoma:
      preliminary results of a phase II trial and propensity score analysis.
AB  - CONTEXT: With recent technical advances in radiotherapy (RT) planning,
      simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) has
      made possible the delivery of high radiation dose to the tumor, minimizing
      surrounding normal tissues. OBJECTIVE: This study aimed to evaluate the clinical
      effectiveness and safety of postoperative SIB-IMRT in patients with
      locoregionally advanced papillary thyroid cancer (PTC). DESIGN AND SETTING: This
      was a propensity score-matched case control study conducted at a tertiary
      referring center. PATIENTS OR OTHER PARTICIPANTS: This study included
      locoregionally advanced patients with PTC (pT4 or N1b) who underwent thyroid
      cancer surgery and radioactive iodine ablation (RIA) followed by postoperative
      SIB-IMRT (RT group) under a phase II trial or no postoperative RT (Non-RT group)
      Intervention: Postoperative SIB-IMRT was the intervention. MAIN OUTCOME MEASURES:
      locoregional relapse-free survival (LRFS) was compared between RT group and Non
      RT group. RESULTS: Multivariate analysis showed that several factors, including
      sex, American Thyroid Association risk category, and use of postoperative RT were
      significantly associated with LRFS in all 201 patients (P < .05 each). In the 118
      propensity score-matched patients, there were no significant differences in
      baseline characteristics between the RT and Non-RT groups, but the LRFS rate was
      significantly higher in the RT than in the Non-RT group (4 y: 100% vs 84.6%, P =
      .002). Overall, SIB-IMRT was well tolerated, with no grade >=3 toxicity, and was
      completed as planned in all patients. CONCLUSIONS: Postoperative SIB-IMRT is
      feasible and effective in improving locoregional control in patients with locally
      advanced PTC. Large-scale randomized studies are warranted.

PMID- 25581598
TI  - Functional characterization of two naturally occurring mutations (Val514Ala and
      Ala575Val) in follicle-stimulating hormone receptor.
AB  - CONTEXT: Inactivating mutations have been reported in subjects with
      primary/secondary amenorrhea, whereas activating mutations are rare and seen only
      in women with ovarian hyperstimulation syndrome (OHSS). In the present study, we
      describe the functional characterization of the two mutations Val(514)Ala (novel
      mutation) and Ala(575)Val in FSH receptor (FSHR) identified in women with OHSS
      developed during in vitro fertilization and primary amenorrhea, respectively.
      OBJECTIVE: The objective of the investigation was to study the effect of
      mutations (514 and 575) on FSHR activity by in vitro functional studies. SETTING:
      The study was conducted at an academic research institute and a private in vitro
      fertilization clinic. METHODS: The site-directed mutagenesis was carried out to
      generate the mutations at position 514 and 575 in pSG5-FSHR construct. Stable
      cell lines expressing wild type or each of the mutant receptor were generated
      using Chinese hamster ovary cells. Functional characteristics of both the mutant
      receptors were assessed by a radioreceptor assay and a cAMP assay. RESULTS: The
      mutant receptor 514 showed increased cell surface expression as compared with the
      wild-type (WT) receptor. Although the hormone binding characteristics were
      similar to the WT receptor, its signaling activity was distinctly higher at lower
      dose of FSH as monitored by a cAMP assay. On the other hand, the mutant receptor
      575 showed lower cell surface expression and higher internalized hormone receptor
      complex. Additionally, a dose-dependent increase in the cAMP accumulation was not
      observed in the case of this mutant as compared with WT. CONCLUSION: OHSS and
      primary amenorrhea observed in the two affected women, respectively, could be
      attributed to the functional characteristics of respective mutant FSHR.

PMID- 25581600
TI  - Luminescent properties of rare earth fully activated apatites, LiRE9(SiO4)6O2 (RE
      = Ce, Eu, and Tb): site selective crystal field effect.
AB  - Novel LiCe9(SiO4)6O2 and LiTb9(SiO4)6O2 compounds have been successfully
      synthesized, and the site selectivity and occupancy of activator ions have been
      estimated including LiEu9(SiO4)6O2 compound. The rare earth (RE) fully occupied
      compounds, as well as the RE partially occupied congeners are required for the
      assessment of site selectivity of RE (activator) ions in apatite-type compounds.
      The splitting energies of the 6H and 4F Wycoff positions of LiRE9(SiO4)6O2 (RE =
      Ce, Eu, and Tb) compounds are calculated based on crystal field theory:
      DeltaECe(6H) = 3849.3 cm(-1), DeltaECe(4F) = 4228.1 cm(-1), DeltaEEu(6H) = 3870.0
      cm(-1), DeltaEEu(4F) = 4092.8 cm(-1), DeltaETb(6H) = 3637.6 cm(-1), DeltaETb(4F)
      = 4396.1 cm(-1), indicating that the splitting energy for the 4F site is larger
      than that for the 6H site in all compounds; thus the absorption energy is higher
      for the 6H site. In apatite-type LiRE9(SiO4)6O2 (RE = Ce, Eu, and Tb) compounds,
      the Ce(3+) ions predominantly occupy the 4F site associated with the absorption
      band around 300 nm at lower Ce(3+) concentration, and then enter the 6H site
      associated the absorption band around 245 nm. For the Eu(3+)-doped compounds, the
      4F site and 6H site are mixed within the charge transfer band (CTB) between 220
      and 350 nm. Eu(3+) ions initially preferentially occupy the 6H site (around 290
      nm) at lower Eu(3+) concentration and subsequently enter the 4F site (around 320
      nm) with increasing Eu(3+) concentration. For the Tb(3+)-doped compounds, the
      absorption due to the two different sites is mixed within f-d absorption band
      between 200 and 300 nm. At lower Tb(3+) concentration, the Tb(3+) ions enter
      favorably 6H site around 240 nm and then enter 4F site around 270 nm. These
      compounds may provide a platform for modeling a new phosphor and application in
      the solid-state lighting field. 

PMID- 25581597
TI  - Neuroendocrine causes of amenorrhea--an update.
AB  - CONTEXT: Secondary amenorrhea--the absence of menses for three consecutive cycles
      -affects approximately 3-4% of reproductive age women, and infertility--the
      failure to conceive after 12 months of regular intercourse--affects approximately
      6-10%. Neuroendocrine causes of amenorrhea and infertility, including functional
      hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these
      cases. OBJECTIVE: In this review, we discuss the physiologic, pathologic, and
      iatrogenic causes of amenorrhea and infertility arising from perturbations in the
      hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus
      extensively on the hormonal mechanisms involved in disrupting the hypothalamic
      pituitary-ovarian axis. CONCLUSIONS: A thorough understanding of the
      neuroendocrine causes of amenorrhea and infertility is critical for properly
      assessing patients presenting with these complaints. Prompt evaluation and
      treatment are essential to prevent loss of bone mass due to hypoestrogenemia
      and/or to achieve the time-sensitive treatment goal of conception.

PMID- 25581599
TI  - Pheochromocytoma and paraganglioma in cyanotic congenital heart disease.
AB  - CONTEXT: Aberrant cellular oxygen sensing is a leading theory for development of
      pheochromocytoma (PHEO) and paraganglioma (PGL). OBJECTIVE: The objective of the
      study was to test the hypothesis that chronic hypoxia in patients with cyanotic
      congenital heart disease (CCHD) increases the risk for PHEO-PGL.
      DESIGN/SETTING/PARTICIPANTS: We investigated the association between CCHD and
      PHEO-PGL with two complementary studies: study 1) an international consortium was
      established to identify congenital heart disease (CHD) patients with a PHEO-PGL
      diagnosis confirmed by pathology or biochemistry and imaging; study 2) the 2000
      2009 Nationwide Inpatient Survey, a nationally representative discharge database,
      was used to determine population-based cross-sectional PHEO-PGL frequency in
      hospitalized CCHD patients compared with noncyanotic CHD and those without CHD
      using multivariable logistic regression adjusted for age, sex, and genetic PHEO
      PGL syndromes. RESULTS: In study 1, we identified 20 PHEO-PGL cases, of which 18
      had CCHD. Most presented with cardiovascular or psychiatric symptoms. Median
      cyanosis duration for the CCHD PHEO-PGL cases was 20 years (range 1-57 y). Cases
      were young at diagnosis (median 31.5 y, range 15-57 y) and 7 of 18 had multiple
      tumors (two bilateral PHEO; six multifocal or recurrent PGL), whereas 11 had
      single tumors (seven PHEO; four PGL). PGLs were abdominal (13 of 17) or head/neck
      (4 of 17). Cases displayed a noradrenergic biochemical phenotype similar to
      reported hypoxia-related PHEO-PGL genetic syndromes but without clinical signs of
      such syndromes. In study 2, hospitalized CCHD patients had an increased
      likelihood of PHEO-PGL (adjusted odds ratio 6.0, 95% confidence interval 2.6
      13.7, P < .0001) compared with those without CHD; patients with noncyanotic CHD
      had no increased risk (odds ratio 0.9, P = .48). CONCLUSIONS: There is a strong
      link between CCHD and PHEO-PGL. Whether these rare diseases coassociate due to
      hypoxic stress, common genetic or developmental factors, or some combination
      requires further investigation.

PMID- 25581601
TI  - Novel mussel-inspired injectable self-healing hydrogel with anti-biofouling
      property.
AB  - A novel mussel-inspired injectable hydrogel with self-healing and anti-biofouling
      capabilities is developed and it possesses great potential as a drug-delivery
      carrier. The hydrogel can heal autonomously from repeated structural damage and
      also effectively prevent non-specific cell attachment and biofilm formation. 

PMID- 25581602
TI  - Across the board: Gabriele Centi.
AB  - In this series of articles, the board members of ChemSusChem discuss recent
      research articles that they consider of exceptional quality and importance for
      sustainability. In this entry, Prof. Gabriele Centi comments on recent results on
      non-oxidative conversion of methane to ethylene and aromatics. The discussion
      takes into account technical, economical, and sustainability perspectives, and
      briefly comments on the role of shale gas in future chemical production
      scenarios. 

PMID- 25581603
TI  - Guest editorial: innovative methods to better manage the clinical, cost, and
      humanistic aspects of bariatric care.

PMID- 25581604
TI  - A prospective, randomized, controlled trial comparing the effects of noncontact,
      low-frequency ultrasound to standard care in healing venous leg ulcers.
AB  - Current scientific evidence suggests venous leg ulcers (VLUs) that do not respond
      to guideline-defined care may have a wound microenvironment that is out of
      physiological balance. A prospective, randomized, controlled, multicenter trial
      was conducted to compare percent wound size reduction, proportions healed, pain,
      and quality-of-life (QOL) outcomes in patients randomized to standard care (SC)
      alone or SC and 40 kHz noncontact, low-frequency ultrasound (NLFU) treatments 3
      times per week for 4 weeks. One hundred, twelve (112) eligible participants with
      documented venous stasis, a VLU >30 days' duration, measuring 4 cm2 to 50 cm2,
      and demonstrated arterial flow were enrolled. Of these, 81 reduced <30% in size
      during the 2-week run-in study phase and were randomized (SC, n = 40; NLFU+SC, n
      = 41). Median age of participants was 59 years; 83% had multiple complex
      comorbidities. Index ulcers were 56% recurrent, with a median duration of 10.3
      months (range 1 month to 204.5 months) and median ulcer area of 11.0 cm2 (range
      3.7 cm2-41.3 cm2). All participants received protocol-defined SC compression (30
      40 mm Hg), dressings to promote a moist wound environment, and sharp debridement
      at the bedside for a minimum of 1 time per week. Ulcer measurements were obtained
      weekly using digital planimetry. Pain and QOL scores were assessed at baseline
      and after 4 weeks of treatment using the Visual Analog Scale and the Short Form
      36 Health Survey. After 4 weeks of treatment, average wound size reduction was
      61.6% +/- 28.9 in the NLFU+SC compared to 45% +/- 32.5 in the SC group (P =
      0.02). Reductions in median (65.7% versus 44.4%, P = 0.02) and absolute wound
      area (9.0 cm2 versus 4.1 cm2, P = 0.003) as well as pain scores (from 3.0 to 0.6
      versus 3.0 to 2.4, P = 0.01) were also significant. NLFU therapy with guideline
      defined standard VLU care should be considered for healing VLUs not responding to
      SC alone. The results of this study warrant further research on barriers to
      healing and the changes occurring in the tissue of the wound to explore theories
      that the microenvironment impacts wounds that do not heal despite provision of
      guideline-defined care. 

PMID- 25581605
TI  - A prospective, randomized, controlled study of a suspension positioning system
      used with elderly bedridden patients with neurogenic fecal incontinence.
AB  - Elderly patients with acute neurological impairment are prone to severe
      disability, fecal incontinence (FI), and resultant complications. A suspension
      positioning system (SPS), based on the orthopedic suspension traction system
      commonly used for conservative treatment of pediatric femoral fracture and
      uncomplicated adult pelvic fracture, was developed to facilitate FI management in
      patients immobilized secondary to an acute neurological condition. To evaluate
      the effectiveness and safety of the system, a prospective, randomized, controlled
      study was conducted between October 2009 and July 2012. Two hundred (200)
      elderly, bedridden, hospitalized patients with acute, nonchronic neurological
      impairment were randomly assigned to receive routine FI nursing care (ie,
      individualized dietary modification, psychological support, health education, and
      social support for caregivers and family members [control group]) or routine
      incontinence care plus the SPS (experimental group) during the day. Rates of
      perianal fecal contamination, skin breakdown, incontinence associated dermatitis,
      pressure ulcer development, and lower urinary tract infection (LUTI) were
      significantly lower in the SPS than in the control group (P <0.05). Length of
      hospitalization and costs of care were also lower in the SPS group (P <0.05).
      Patient quality-of-life (QoL) and FI QoL scores were similar at baseline but
      significantly higher (better) at the 6-month follow-up interview in the SPS than
      in the control group (P <0.05). In this study, the rate of FI-associated
      morbidities was lower and 6-month patient QoL scores were higher in the SPS than
      in the control group. No adverse events were observed, and all patients completed
      the study. Further clinical studies are needed to examine the long-term effects
      of SPS use among neurologically impaired FI patients.

PMID- 25581606
TI  - Clinician challenges in providing health care for a morbidly obese family member:
      a bariatric case study.
AB  - Morbid obesity is a chronic disease affecting millions of Americans. The disorder
      is likely to increase in prevalence because currently one third of the American
      population is obese. Many factors are associated with morbid obesity, including
      psychological (eg, depression), physiological (eg, hypothyroidism) mechanisms,
      sleep disorders (eg, sleep apnea), drug therapy (antidepressants, antidiabetic
      agents, steroids), and genetics. Increasing numbers of morbidly obese patients
      are requiring critical care, presenting major challenges to professional staff
      across the disciplines. This manuscript presents a case study describing the
      experiences of a morbidly obese woman in the final years of her life from the
      perspective of her health professional relative. The patient typifies many of the
      major risk factors for morbid obesity; her story reveals many of the issues faced
      as she revolved in and out of the critical care and acute care system. Her
      substantive health problems affected multiple body systems and included
      hypothyroidism, congestive heart failure, hyperlipidemia, and subclinical
      Cushing's Syndrome, likely related to previous medical therapy (cortisone) for
      rheumatic fever in childhood. The case description addresses many integumentary
      system issues the patient experienced; skin injuries and infections that can pose
      serious life-threatening situations for the morbidly obese patient must be
      prevented or treated efficiently. Health professionals can learn a great deal and
      improve the care they provide by listening to morbidly obese patients. 

PMID- 25581607
TI  - Inhibition of anandamide hydrolysis enhances noradrenergic and GABAergic
      transmission in the prefrontal cortex and basolateral amygdala of rats subjected
      to acute swim stress.
AB  - Limbic forebrain endocannabinoid (eCB) signaling is critically involved in stress
      integration by modulating neurotransmitters release. The purpose of this study
      was to examine, by brain microdialysis, the effects of fatty acid amide hydrolase
      (FAAH) inhibition on noradrenergic and gamma-aminobutyric acid (GABA)-ergic
      neurotransmission in the prefrontal cortex (PFC) and basolateral amygdala (BLA)
      of rats subjected to a 20-min swim stress. Microdialysis started on stress- and
      drug-naive rats that were treated with the FAAH inhibitor URB597 (0.1 or 0.3
      mg/kg) 30 min before undergoing the stress procedure. Dialysate samples were
      collected every 20 min from the beginning of the experiment. Concentrations of
      noradrenaline (NA) and GABA were determined by HPLC coupled to electrochemical
      and fluorescence detection, respectively. We found that neither URB597 treatment
      nor 20 min of swim stress exposure per se altered NA and GABA extracellular
      levels in PFC or BLA. Interestingly, rats treated with 0.1 mg/kg of URB597
      followed by 20 min of stress showed significantly higher NA and GABA levels in
      PFC and BLA. These effects were absent in rats treated with 0.3 mg/kg URB597,
      indicating a dose-specific effect. Moreover, we found that the pretreatment with
      the CB1 receptor antagonist rimonabant blocked the URB597 effects on NA and GABA
      release in PFC and BLA of animals subjected to forced swimming. The present study
      might provide an important first step toward understanding the mechanisms through
      which URB597 modulates stress-induced neuroendocrine secretion and behavioral
      coping strategies.

PMID- 25581608
TI  - Percutaneous extraction of inadvertently placed left-sided pacemaker leads with
      complete cerebral embolic protection.
AB  - Lead wire malposition is a known, but rare complication of permanent pacemaker or
      defibrillator implantation. The actual incidence and prevalence is unknown and
      management options for inadvertent left ventricular lead malposition have not
      been uniform. Current recommendations include systemic anticoagulation with
      warfarin or surgical lead removal with circulatory arrest for compelling clinical
      scenarios. Percutaneous left-sided lead extraction is contraindicated due to the
      potentially increased risk of thromboembolic complications associated with this
      procedure. To our knowledge, this is the first report of percutaneous extraction
      of inadvertently placed left ventricular and left atrial endocardial pacemaker
      leads with flow-preserving complete cerebral embolic protection. We also review
      the current literature regarding the incidence, management, and percutaneous
      extraction of left-sided cardiac leads.

PMID- 25581611
TI  - Reducing the risk of legionellosis in stem cell transplant recipients.

PMID- 25581609
TI  - The potential of neurotensin secreted from neuroendocrine tumor cells to promote
      gelsolin-mediated invasiveness of prostate adenocarcinoma cells.
AB  - Neuroendocrine (NE) cells in prostate cancer have been shown to be associated
      with the progression of prostate cancer. However, little is known about the
      molecular basis of this association. We have previously demonstrated that NE
      cells promote metastasis of a human prostate cancer cell line (LNCaP) with
      overexpression of the gelsolin gene. The purpose of this study was to investigate
      the interactions between NE cells and LNCaP cells and the involvement of gelsolin
      in contributing to the invasive potential of LNCaP cells. In addition, we
      examined whether neurotensin induced gelsolin-mediated invasion. We used the NE
      cell line NE-CS that was established from the prostate of the LPB-Tag 12T-10
      transgenic mouse. Small interfering RNA (siRNA) targeting gelsolin or not
      targeting it was transfected into LNCaP cells. Cell invasion was assessed by
      Matrigel invasion assay. The supernatant of NE-CS cells and neurotensin induced
      the transformation of LNCaP cells. Neurotensin was observed in the supernatant of
      NE-CS cells but not in LNCaP cells. The siRNA targeting of gelsolin resulted in
      inhibition of invasion of LNCaP cells in the culture medium with neurotensin
      added, and in the supernatant of NE-CS cells with epidermal growth factor. The
      invasive potential of LNCaP cells enhanced by neurotensin or the supernatant of
      NE-CS cells through neurotensin receptor 1 (NTSR1) was blocked by a phospholipase
      Cgamma inhibitor and an intracellular calcium chelator, with concomitant gelsolin
      suppression. This study indicates that NE cells and neurotensin induce gelsolin
      mediated invasion of LNCaP cells through NTSR1 activation. 

PMID- 25581610
TI  - Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in
      association with inhibition of oxidative stress in rats.
AB  - The role of endogenous sulfur dioxide (SO2), an efficient gasotransmitter
      maintaining homeostasis, in the development of acute lung injury (ALI) remains
      unidentified. We aimed to investigate the role of endogenous SO2 in the
      pathogenesis of ALI. An oleic acid (OA)-induced ALI rat model was established.
      Endogenous SO2 levels, lung injury, oxidative stress markers and apoptosis were
      examined. OA-induced ALI rats showed a markedly downregulated endogenous
      SO2/aspartate aminotransferase 1 (AAT1)/AAT2 pathway and severe lung injury.
      Chemical colorimetry assays demonstrated upregulated reactive oxygen species
      generation and downregulated antioxidant capacity in OA-induced ALI rats.
      However, SO2 increased endogenous SO2 levels, protected against oxidative stress
      and alleviated ALI. Moreover, compared with OA-treated cells, in human alveolar
      epithelial cells SO2 downregulated O2(-) and OH(-) generation. In contrast, L
      aspartic acid-beta-hydroxamate (HDX, Sigma-Aldrich Corporation), an inhibitor of
      endogenous SO2 generating enzyme, promoted free radical generation, upregulated
      poly (ADP-ribose) polymerase expression, activated caspase-3, as well as promoted
      cell apoptosis. Importantly, apoptosis could be inhibited by the free radical
      scavengers glutathione (GSH) and N-acetyl-L-cysteine (NAC). The results suggest
      that SO2/AAT1/AAT2 pathway might protect against the development of OA-induced
      ALI by inhibiting oxidative stress. 

PMID- 25581613
TI  - Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through
      inhibiting Hedgehog signaling pathway.
AB  - JK184 can specially inhibit Gli in the Hedgehog (Hh) pathway, which showed great
      promise for cancer therapeutics. For developing aqueous formulation and improving
      anti-tumor activity of JK184, we prepared JK184 encapsulated MPEG-PCL micelles by
      the solid dispersion method without using surfactants or toxic organic solvents.
      The cytotoxicity and cellular uptake of JK184 micelles were both increased
      compared with the free drug. JK184 micelles induced more apoptosis and blocked
      proliferation of Panc-1 and BxPC-3 tumor cells. In addition, JK184 micelles
      exerted a sustained in vitro release behavior and had a stronger inhibitory
      effect on proliferation, migration and invasion of HUVECs than free JK184.
      Furthermore, JK184 micelles had stronger tumor growth inhibiting effects in
      subcutaneous Panc-1 and BxPC-3 tumor models. Histological analysis showed that
      JK184 micelles improved anti-tumor activity by inducing more apoptosis,
      decreasing microvessel density and reducing expression of CD31, Ki67, and VEGF in
      tumor tissues. JK184 micelles showed a stronger inhibition of Gli expression in
      Hh signaling, which played an important role in pancreatic carcinoma.
      Furthermore, circulation time of JK184 in blood was prolonged after entrapment in
      polymeric micelles. Our results suggested that JK184 micelles are a promising
      drug candidate for treating pancreatic tumors with a highly inhibitory effect on
      Hh activity. 

PMID- 25581612
TI  - Comprehensive appraisal of magnetic resonance imaging findings in sustained
      rheumatoid arthritis remission: a substudy.
AB  - OBJECTIVE: To evaluate the effect of sustained American College of Rheumatology
      (ACR)/European League Against Rheumatism (EULAR) Boolean remission on residual
      joint inflammation assessed by magnetic resonance imaging (MRI) and to
      secondarily evaluate other clinical definitions of remission, within an early
      seropositive rheumatoid arthritis (RA) cohort. METHODS: A subcohort of 118 RA
      patients was enrolled from patients who completed the 2-year, double-blind
      randomized Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial.
      Patients received a single contrast-enhanced 1.5T MRI of their most involved
      wrist. Two readers scored MRIs for synovitis, osteitis, tenosynovitis, and
      erosions. Clinical assessments were performed every 3 months during the trial and
      at time of MRI. RESULTS: The subcohort was 92% seropositive with mean age 51
      years, duration 4.1 months, and Disease Activity Score in 28 joints using the
      erythrocyte sedimentation rate 5.8 at TEAR entry. Total MRI inflammatory scores
      (tenosynovitis + synovitis + osteitis) were lower among patients in clinical
      remission. Lower MRI scores were correlated with longer duration of Clinical
      Disease Activity Index (CDAI) remission (rho = 0.22, P = 0.03). At the time of
      MRI, 89 patients had no wrist pain/tenderness/swelling; however, all 118 patients
      had MRI evidence of residual joint inflammation after 2 years. No statistically
      significant differences in damage or MRI inflammatory scores were observed across
      treatment groups. CONCLUSION: This is the first detailed appraisal describing the
      relationship between clinical remission cut points and MRI inflammatory scores
      within an RA randomized controlled trial. The most stringent remission criteria
      (2011 ACR/EULAR and CDAI) best differentiate the total MRI inflammatory scores.
      These results document that 2 years of triple therapy or tumor necrosis factor
      plus methotrexate treatment in early RA does not eliminate MRI evidence of joint
      inflammation.

PMID- 25581614
TI  - Antimicrobial activity and mechanism of action of a novel cationic alpha-helical
      octadecapeptide derived from alpha-amylase of rice.
AB  - AmyI-1-18, an octadecapeptide derived from alpha-amylase (AmyI-1) of rice (Oryza
      sativa L. japonica), is a novel cationic alpha-helical antimicrobial peptide
      (AMP) that contains two lysine and two arginine residues. The antimicrobial
      activity of AmyI-1-18 against human pathogens was quantitatively evaluated using
      a chemiluminescence method that measures ATP derived from viable cells. Of the
      ten kinds of human pathogens, AmyI-1-18 exhibited antimicrobial activity against
      nine. Its 50% growth-inhibitory concentrations (ICs50 ) against Porphyromonas
      gingivalis, Propionibacterium acnes, Pseudomonas aeruginosa, Candida albicans,
      and Streptococcus mutans were 13, 19, 50, 64, and 77 MUM, respectively. AmyI-1-18
      had little or no hemolytic activity even at 500 MUM, and showed negligible
      cytotoxicity up to 1200 MUM. The degree of 3,3'-dipropylthiadicarbocyanine iodide
      release from P. gingivalis cells induced by the addition of AmyI-1-18 was
      significantly lower than that induced by the addition of melittin. Flow
      cytometric analysis showed that the percentages of P. aeruginosa, S. mutans, and
      C. albicans cells stained with propidium iodide (PI), a DNA-intercalating dye,
      were 89%, 43%, and 3%, respectively, when AmyI-1-18 was added at a concentration
      equal to its 4*IC50 . Therefore, the antimicrobial activity of AmyI-1-18 against
      P. aeruginosa and S. mutans appears to be mainly attributable to its membrane
      disrupting activity. In contrast, its antimicrobial activity against P.
      gingivalis and C. albicans most likely depends upon interactions with
      intracellular targets other than their cell membranes. Collectively, these
      results indicate that AmyI-1-18 is useful as a safe and potent AMP against the
      pathogens described above in many fields of healthcare.

PMID- 25581615
TI  - (1) H NMR spectroscopy of glioblastoma stem-like cells identifies alpha
      aminoadipate as a marker of tumor aggressiveness.
AB  - Patients suffering from glioblastoma multiforme (GBM) face a poor prognosis with
      median survival of about 14 months. High recurrence rate and failure of
      conventional treatments are attributed to the presence of GBM cells with stem
      like properties (GSCs). Metabolite profiles of 42 GSC lines established from the
      tumor tissue of adult GBM patients were screened with (1) H NMR spectroscopy and
      compared with human neural progenitor cells from human adult olfactory bulb (OB
      NPCs) and from the developing human brain (HNPCs). A first subset (n=12) of GSCs
      exhibited a dramatic accumulation of the metabolite alpha-aminoadipate
      (alphaAAD), product of the oxidation of alpha-aminoadipic semialdehyde catalyzed
      by the ALDH7A1 aldehyde dehydrogenase (ALDH) family in lysine catabolism.
      alphaAAD was low/not detectable in a second GSC subset (n=13) with the same
      neural metabolic profile as well as in a third GSC subset (n=17) characterized by
      intense lipid signals. Likewise, alphaAAD was not detected in the spectra of OB
      NPCs or HNPCs. Inhibition of mitochondrial ATP synthase by oligomycin treatment
      revealed that the lysine degradative pathway leading to alphaAAD formation
      proceeds through saccharopine, as usually observed in developing brain. Survival
      curves indicated that high alphaAAD levels in GSCs significantly correlated with
      poor patient survival, similarly to prostate and non-small-cell-lung cancers,
      where activity of ALDH7A1 correlates with tumor aggressiveness.

PMID- 25581616
TI  - Oral Delivery of Bovine Lactoferrin Using Pectin- and Chitosan-Modified Liposomes
      and Solid Lipid Particles: Improvement of Stability of Lactoferrin.
AB  - A critical problem associated with delivery of bovine lactoferrin (bLf) by the
      oral route is low bioavailability, which is derived from the enzymatic
      degradation in the gastrointestinal tract and poor permeation across the
      intestinal epitheliums. Particulate carrier systems have been identified to
      protect bLf against proteolysis via encapsulation. This study aimed to evaluate
      the physico-chemical stability of bLf-loaded liposomes and solid lipid particles
      (SLPs) modified by pectin and chitosan when exposed to various stress conditions.
      Transmission electron microscopy results showed liposomes and SLPs had a classic
      shell-core structure with polymer layers surrounded on surface, but the structure
      appeared to be partially broken after digestion in simulated intestinal fluid
      (SIF). Although HPLC and sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis methods qualitatively and quantitatively described either
      liposomes or SLPs could retain intact bLf against proteolysis in SIF to some
      extent, all liposome formulations showed rapid rate of lipolysis mediated by
      pancreatic enzymes. On the other hand, all SLP formulations showed higher heat
      resistance and greater electrolyte tolerance compared to liposome formulations.
      After 180 days storage time, liposome-loaded bLf was completely degraded, whereas
      almost 30% of intact bLf still remained in SLP formulations. Overall, SLPs are
      considered as primary choice for oral bLf delivery. 

PMID- 25581617
TI  - Coping with HIV in a culture of silence: results of a body-mapping workshop.
AB  - The image shows a body map created by a young HIV-positive African woman living
      in Belgium. It was created as part of a body-mapping workshop with 10 sub-Saharan
      African migrants living with HIV. The short text provided with the image
      describes experiences and results of this workshop. The participants experienced
      body-mapping as a valuable tool in coping with HIV and it supported them in
      disclosing HIV to others.

PMID- 25581619
TI  - Current practices in venous thromboembolism prophylaxis in otolaryngology-head
      and neck surgery.
AB  - BACKGROUND: There has been recent investigation into the incidence of venous
      thromboembolism in otolaryngology, but the current utilization of venous
      thromboembolic (VTE) prophylaxis among practicing otolaryngologists remains
      largely unknown. METHODS: A survey of 26 questions was emailed to 4376
      otolaryngologists. RESULTS: A total of 4376 surveys were sent and 676 were
      returned for a response rate of 15.4%. Intraoperative prophylaxis was used by 535
      respondents (83%), either with intermittent pneumatic compression (91.8%),
      compression stockings (35.9%), or low-molecular-weight heparin (LMWH; 12.3%).
      Postoperative prophylaxis was used by 540 respondents (85.4%), either with early
      ambulation (87.8%), intermittent pneumatic compression (85.4%), compression
      stockings (43.3%), or LMWH (42.4%). The vast majority (88.3%) stated they would
      find thromboprophylaxis guidelines released by the American Academy of
      Otolaryngology - Head and Neck Surgery to be helpful. CONCLUSION: Current
      practices in venous thromboembolism prophylaxis vary widely among the
      otolaryngology community. A set of clear specialty-specific guidelines may be
      helpful. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E341-E345, 2016.

PMID- 25581618
TI  - Autograft HIV-DNA load predicts HIV-1 peripheral reservoir after stem cell
      transplantation for AIDS-related lymphoma patients.
AB  - Autologous stem cell transplantation (ASCT) is a widely used procedure for AIDS
      related lymphomas, and it represents an opportunity to evaluate strategies curing
      HIV-1 infection. The association of autograft HIV-DNA load with peripheral blood
      HIV-1 reservoir before ASCT and its contribution in predicting HIV-1 reservoir
      size and stability during combination antiretroviral therapy (cART) after
      transplantation are unknown. Aiming to obtain information suggesting new
      functional cure strategies by ASCT, we retrospectively evaluated HIV-DNA load in
      autograft and in peripheral blood before and after transplantation in 13 cART
      treated HIV-1 relapse/refractoring lymphoma patients. Among them seven
      discontinued cART after autograft infusion. HIV-DNA was evaluated by a sensitive
      quantitative real-time polymerase chain reaction (PCR). After debulking
      chemotherapy/mobilization, the autograft HIV-1 reservoir was higher than and not
      associated with the peripheral HIV-1 reservoir at baseline [median 215 HIV-DNA
      copies/10(6) autograft mononuclear cells, range 13-706 vs. 82 HIV-DNA
      copies/10(6) peripheral blood mononuclear cells (PBMCs), range 13-479, p = 0.03].
      After high dose chemotherapy and autograft infusion, HIV-DNA levels reached a
      plateau between month 6 and 12 of follow-up. No association was found between
      peripheral HIV-DNA levels at baseline and after infusion in both cART
      interrupting and not interrupting patients. Only in the last subgroup, a stable
      significant linear association between autograft and peripheral blood HIV-1
      reservoir emerged from month 1 (R(2) = 0.84, p = 0.01) to month 12 follow-up
      (R(2) = 0.99, p = 0.0005). In summary, autograft HIV-1 reservoir size could be
      influenced by the mobilization phase and predicts posttransplant peripheral HIV-1
      reservoir size in patients on continuous cART. These findings could promote new
      research on strategies reducing the HIV-1 reservoir by using the ASCT procedure.

PMID- 25581620
TI  - Eukaryotic tRNAs fingerprint invertebrates vis-a-vis vertebrates.
AB  - During translation, aminoacyl-tRNA synthetases recognize the identities of the
      tRNAs to charge them with their respective amino acids. The conserved identities
      of 58,244 eukaryotic tRNAs of 24 invertebrates and 45 vertebrates in genomic tRNA
      database were analyzed and their novel features extracted. The internal promoter
      sequences, namely, A-Box and B-Box, were investigated and evidence gathered that
      the intervention of optional nucleotides at 17a and 17b correlated with the
      optimal length of the A-Box. The presence of canonical transcription terminator
      sequences at the immediate vicinity of tRNA genes was ventured. Even though non
      canonical introns had been reported in red alga, green alga, and nucleomorph so
      far, fairly motivating evidence of their existence emerged in tRNA genes of other
      eukaryotes. Non-canonical introns were seen to interfere with the internal
      promoters in two cases, questioning their transcription fidelity. In a first of
      its kind, phylogenetic constructs based on tRNA molecules delineated and built
      the trees of the vast and diverse invertebrates and vertebrates. Finally, two
      tRNA models representing the invertebrates and the vertebrates were drawn, by
      isolating the dominant consensus in the positional fluctuations of nucleotide
      compositions. 

PMID- 25581621
TI  - In-clinic endoscopic polypectomy for chronic rhinosinusitis with polyps: a
      treatment strategy pilot study in ten adults.

PMID- 25581622
TI  - Transcatheter arterial embolization is the first-line therapy of choice in peptic
      ulcer bleeding not responding to endoscopic therapy.
AB  - OBJECTIVE: In 5-10% of patients with peptic ulcer bleeding (PUB) it is impossible
      to achieve endoscopic hemostasis because of severe bleeding. These patients have
      traditionally been treated surgically. Transcatheter arterial embolization (TAE)
      may, however, be associated with a better outcome because of the less-invasive
      nature of the procedure. The aim of the present study was to identify the
      treatment of choice in endoscopy-refractory PUB. MATERIALS AND METHODS: A
      retrospective study. Consecutive patients treated with surgery or TAE for
      endoscopy-refractory PUB during a period of 16 years at a university hospital
      were included. Primary hemostasis, rebleeding rate, mortality, and complications
      were assessed. Mortality was compared between groups after adjustment for age,
      comorbidity, and anemia using logistic regression analyses. Comorbidity was
      quantified using the Charlson comorbidity index (CCI). RESULTS: One hundred and
      eighteen patients were included. Patients treated with TAE had a higher CCI
      (mean: 2.33 vs 1.42; p = .003), and more severe anemia (mean: 6.8 vs 7.9 g/dl; p
      = .007) compared with patients treated with surgery. Surgery was associated with
      a higher rate of primary hemostasis (100% vs 91%; p = .007), lower rate of
      rebleeding (15% vs 40%; p = .004) but also higher rate of complications (60% vs
      38%; p = .02) than TAE. Surgery was associated with an increased mortality (Odds
      ratio: 3.05; p = .033) when adjusting for confounding factors and excluding
      patients (n = 3) who were not candidates for both interventions. CONCLUSIONS: We
      propose use of TAE as first-line therapy in these patients as it may be
      associated with lower mortality and lower rate of complications compared with
      surgery.

PMID- 25581623
TI  - Improvement of overlapping nuclear track densitometry.
AB  - Detection of tracks produced by alpha particles, protons or nuclear fission
      fragments in plastic detectors, viz., solid-state nuclear track detectors,
      constitutes a very important tool in various areas. It is not easy for humans to
      count CR-39 nuclear tracks manually, especially when the track density is very
      high. An automated computer program called KTTMS2, written in C++ and running
      with a user friendly interface, has been developed for recognition and parametric
      measurements of etched tracks in images captured from the surface of solid-state
      nuclear track detectors. Well-known edge detection methods were applied to
      estimate the precision and accuracy of nuclear track densitometry using the CR-39
      detector. Among the various routine edge detection methods, the Canny method was
      chosen because it was the most accurate technique. Because accuracy becomes more
      important as the track density increases, this allows more overlapping tracks to
      be detected. KTTMS2 (the proposed system) has an efficiency of 95% and can
      identify the noise as a background track (5%). Experimental results showed that
      the error percentage was reduced from 7.63% to 3.23% for high-density tracks when
      the count was adjusted by the estimated overlapping tracks. 

PMID- 25581624
TI  - Predictors of emotional eating during adolescents' transition to college: does
      body mass index moderate the association between stress and emotional eating?
AB  - OBJECTIVE: This study sought to (1) examine perceived stress and resources to
      cope with stress as predictors of emotional eating during the transition to
      college and (2) determine whether body mass index (BMI) moderated the emotional
      eating-stress relationship. PARTICIPANTS: Participants were 97 college freshmen
      (73% female; BMI: M = 25.3 kg/m(2), SD = 5.7 kg/m(2)). Research was conducted in
      September 2012. METHODS: Participants completed the Perceived Stress Scale,
      Emotional Eating Scale, and Eating and Appraisal Due to Emotions and Stress
      Questionnaire during the first month of college. Height and weight were measured
      objectively. RESULTS: BMI moderated the relationship between perceived stress and
      emotional eating. Higher stress predicted greater emotional eating for the lower
      BMI groups, but not the highest group. Greater resources to cope with stress
      predicted lower emotional eating. CONCLUSIONS: Greater perceived stress and
      poorer resources to cope with stress may contribute to emotional eating during
      the transition to college. The relationship between perceived stress and
      emotional eating may vary by BMI.

PMID- 25581626
TI  - Epitaxy of semiconductor-superconductor nanowires.
AB  - Controlling the properties of semiconductor/metal interfaces is a powerful method
      for designing functionality and improving the performance of electrical devices.
      Recently semiconductor/superconductor hybrids have appeared as an important
      example where the atomic scale uniformity of the interface plays a key role in
      determining the quality of the induced superconducting gap. Here we present
      epitaxial growth of semiconductor-metal core-shell nanowires by molecular beam
      epitaxy, a method that provides a conceptually new route to controlled electrical
      contacting of nanostructures and the design of devices for specialized
      applications such as topological and gate-controlled superconducting electronics.
      Our materials of choice, InAs/Al grown with epitaxially matched single-plane
      interfaces, and alternative semiconductor/metal combinations allowing epitaxial
      interface matching in nanowires are discussed. We formulate the grain growth
      kinetics of the metal phase in general terms of continuum parameters and
      bicrystal symmetries. The method realizes the ultimate limit of uniform
      interfaces and seems to solve the soft-gap problem in superconducting hybrid
      structures. 

PMID- 25581625
TI  - A design strategy for intramolecular singlet fission mediated by charge-transfer
      states in donor-acceptor organic materials.
AB  - The ability to advance our understanding of multiple exciton generation (MEG) in
      organic materials has been restricted by the limited number of materials capable
      of singlet fission. A particular challenge is the development of materials that
      undergo efficient intramolecular fission, such that local order and strong
      nearest-neighbour coupling is no longer a design constraint. Here we address
      these challenges by demonstrating that strong intrachain donor-acceptor
      interactions are a key design feature for organic materials capable of
      intramolecular singlet fission. By conjugating strong-acceptor and strong-donor
      building blocks, small molecules and polymers with charge-transfer states that
      mediate population transfer between singlet excitons and triplet excitons are
      synthesized. Using transient optical techniques, we show that triplet populations
      can be generated with yields up to 170%. These guidelines are widely applicable
      to similar families of polymers and small molecules, and can lead to the
      development of new fission-capable materials with tunable electronic structure,
      as well as a deeper fundamental understanding of MEG. 

PMID- 25581627
TI  - Field-tunable spin-density-wave phases in Sr3Ru2O7.
AB  - The conduction electrons in a metal experience competing interactions with each
      other and the atomic nuclei. This competition can lead to many types of magnetic
      order in metals. For example, in chromium the electrons order to form a spin
      density-wave (SDW) antiferromagnetic state. A magnetic field may be used to
      perturb or tune materials with delicately balanced electronic interactions. Here,
      we show that the application of a magnetic field can induce SDW magnetic order in
      a quasi-2D metamagnetic metal, where none exists in the absence of the field. We
      use magnetic neutron scattering to show that the application of a large (B ~ 8 T)
      magnetic field to the perovskite metal Sr3Ru2O7 (refs 3-7) can be used to tune
      the material through two magnetically ordered SDW states. The ordered states
      exist over relatively small ranges in field (?0.4 T), suggesting that their
      origin is due to a new mechanism related to the electronic fine structure near
      the Fermi energy, possibly combined with the stabilizing effect of magnetic
      fluctuations. The magnetic field direction is shown to control the SDW domain
      populations, which naturally explains the strong resistivity anisotropy or
      'electronic nematic' behaviour observed in this material.

PMID- 25581628
TI  - Experimental demonstration of hybrid improper ferroelectricity and the presence
      of abundant charged walls in (Ca,Sr)3Ti2O7 crystals.
AB  - On the basis of successful first-principles predictions of new functional
      ferroelectric materials, a number of new ferroelectrics have been experimentally
      discovered. Using trilinear coupling of two types of octahedron rotation, hybrid
      improper ferroelectricity has been theoretically predicted in ordered perovskites
      and the Ruddlesden-Popper compounds (Ca3Ti2O7, Ca3Mn2O7 and
      (Ca/Sr/Ba)3(Sn/Zr/Ge)2O7). However, the ferroelectricity of these compounds has
      never been experimentally confirmed and even their polar nature has been under
      debate. Here we provide the first experimental demonstration of room-temperature
      switchable polarization in bulk crystals of Ca3Ti2O7, as well as Sr-doped
      Ca3Ti2O7. Furthermore, (Ca, Sr)3Ti2O7 is found to exhibit an intriguing
      ferroelectric domain structure resulting from orthorhombic twins and (switchable)
      planar polarization. The planar domain structure accompanies abundant charged
      domain walls with conducting head-to-head and insulating tail-to-tail
      configurations, which exhibit a conduction difference of two orders of magnitude.
      These discoveries provide new research opportunities, not only for new stable
      ferroelectrics of Ruddlesden-Popper compounds, but also for meandering conducting
      domain walls formed by planar polarization. 

PMID- 25581629
TI  - Current medication practice and tracheal intubation safety outcomes from a
      prospective multicenter observational cohort study.
AB  - OBJECTIVES: Tracheal intubation in PICUs is often associated with adverse
      tracheal intubation-associated events. There is a paucity of data regarding
      medication selection for safe tracheal intubations in PICUs. Our primary
      objective was to evaluate the association of medication selection on specific
      tracheal intubation-associated events across PICUs. DESIGN: Prospective
      observational cohort study. SETTING: Nineteen PICUs in North America. SUBJECTS:
      Critically ill children requiring tracheal intubation. INTERVENTIONS: None.
      MEASUREMENT AND MAIN RESULTS: Using the National Emergency Airway Registry for
      Children, tracheal intubation quality improvement data were prospectively
      collected from July 2010 to March 2013. Patient, provider, and practice
      characteristics including medications and dosages were collected. Adverse
      tracheal intubation-associated events were defined a priori. A total of 3,366
      primary tracheal intubations were reported. Adverse tracheal intubation
      associated events occurred in 593 tracheal intubations (18%). Fentanyl and
      midazolam were the most commonly used induction medications (64% and 58%,
      respectively). Neuromuscular blockade was used in 92% of tracheal intubation with
      the majority using rocuronium (64%) followed by vecuronium (20%). Etomidate and
      succinylcholine were rarely used (1.6% and 0.7%, respectively). Vagolytics were
      administered in 37% of tracheal intubations (51% in infants; 28% in > 1 yr old; p
      < 0.001). Ketamine was used in 27% of tracheal intubations but more often for
      tracheal intubations in patients with unstable hemodynamics (39% vs 25%; p <
      0.001). However, ketamine use was not associated with lower prevalence of new
      hypotension (ketamine 8% vs no ketamine 14%; p = 0.08). CONCLUSIONS: In this
      large, pediatric multicenter registry, fentanyl, midazolam, and ketamine were the
      most commonly used induction agents, and the majority of tracheal intubations
      involved neuromuscular blockade. Ketamine use was not associated with lower
      prevalence of hypotension.

PMID- 25581630
TI  - Autologous bone marrow mononuclear cells reduce therapeutic intensity for severe
      traumatic brain injury in children.
AB  - OBJECTIVES: The devastating effect of traumatic brain injury is exacerbated by an
      acute secondary neuroinflammatory response, clinically manifest as elevated
      intracranial pressure due to cerebral edema. The treatment effect of cell-based
      therapies in the acute post-traumatic brain injury period has not been clinically
      studied although preclinical data demonstrate that bone marrow-derived
      mononuclear cell infusion down-regulates the inflammatory response. Our study
      evaluates whether pediatric traumatic brain injury patients receiving IV
      autologous bone marrow-derived mononuclear cells within 48 hours of injury
      experienced a reduction in therapeutic intensity directed toward managing
      elevated intracranial pressure relative to matched controls. DESIGN: The study
      was a retrospective cohort design comparing pediatric patients in a phase I
      clinical trial treated with IV autologous bone marrow-derived mononuclear cells
      (n = 10) to a control group of age- and severity-matched children (n = 19).
      SETTING: The study setting was at Children's Memorial Hermann Hospital, an
      American College of Surgeons Level 1 Pediatric Trauma Center and teaching
      hospital for the University of Texas Health Science Center at Houston from 2000
      to 2008. PATIENTS: Study patients were 5-14 years with postresuscitation Glasgow
      Coma Scale scores of 5-8. INTERVENTIONS: The treatment group received 6 million
      autologous bone marrow-derived mononuclear cells/kg body weight IV within 48
      hours of injury. The control group was treated in an identical fashion, per
      standard of care, guided by our traumatic brain injury management protocol,
      derived from American Association of Neurological Surgeons guidelines.
      MEASUREMENTS AND MAIN RESULTS: The primary measure was the Pediatric Intensity
      Level of Therapy scale used to quantify treatment of elevated intracranial
      pressure. Secondary measures included the Pediatric Logistic Organ Dysfunction
      score and days of intracranial pressure monitoring as a surrogate for length of
      neurointensive care. A repeated-measure mixed model with marginal linear
      predictions identified a significant reduction in the Pediatric Intensity Level
      of Therapy score beginning at 24 hours posttreatment through week 1 (p < 0.05).
      This divergence was also reflected in the Pediatric Logistic Organ Dysfunction
      score following the first week. The duration of intracranial pressure monitoring
      was 8.2 +/- 1.3 days in the treated group and 15.6 +/- 3.5 days (p = 0.03) in the
      time-matched control group. CONCLUSIONS: IV autologous bone marrow-derived
      mononuclear cell therapy is associated with lower treatment intensity required to
      manage intracranial pressure, associated severity of organ injury, and duration
      of neurointensive care following severe traumatic brain injury. This may
      corroborate preclinical data that autologous bone marrow-derived mononuclear cell
      therapy attenuates the effects of inflammation in the early post-traumatic brain
      injury period.

PMID- 25581632
TI  - Fluid overload at 48 hours is associated with respiratory morbidity but not
      mortality in a general PICU: retrospective cohort study.
AB  - OBJECTIVE: Recent evidence suggests that fluid overload may be deleterious to
      critically ill children. The purpose of this study was to investigate the
      association of early fluid overload with respiratory morbidity and mortality in
      patients admitted to a general PICU. DESIGN: Retrospective cohort study. SETTING:
      Single, tertiary referral PICU. PATIENTS SIX HUNDRED THIRTY-SIX: patients aged 0
      16 years invasively ventilated at 48 hours post admission, admitted between April
      1, 2009, and March 31, 2013. MEASUREMENTS AND MAIN RESULTS: Data collected
      included demographics, diagnosis, Pediatric Index of Mortality 2 score, and fluid
      overload percent at 48 hours from admission. Fluid overload percent was
      calculated as (cumulative fluid in - cumulative fluid out (L))/hospital admission
      weight (kg) * 100%. Outcome measures were oxygenation index at 48 hours from
      admission, death, and invasive ventilation days in survivors. Data are reported
      as median (interquartile range) and were analyzed using nonparametric tests. The
      median age was 1.05 years (0.3-4.2 yr). Fifty-three patients (8%) died. Median
      duration of ventilation in survivors was 5 days (3-8 d). Fluid overload percent
      correlated significantly with oxygenation index (Spearman rho, 0.318; p < 0.0001)
      and with invasive ventilation days in survivors (Spearman rho, 0.274; p <
      0.0001). There was no significant difference in fluid overload percent between
      survivors and nonsurvivors. Regression analysis demonstrated that fluid overload
      percent was a significant predictor of both oxygenation index at 48 hours (p <
      0.001) and invasive ventilation days (p = 0.002). CONCLUSIONS: Fluid overload at
      48 hours was associated with oxygenation index at 48 hours and invasive
      ventilation days in survivors in a general PICU population. There was no
      association of fluid overload at 48 hours with mortality.

PMID- 25581633
TI  - Association of timing of tracheostomy on clinical outcomes in PICU patients.
AB  - OBJECTIVES: Tracheostomy is a common procedure in the ICU when prolonged
      mechanical ventilation is expected. Although adult data show morbidity and
      mortality benefits over translaryngeal intubation, there is no consensus on
      optimal timing. In the pediatric population, there is sparse data regarding
      morbidities associated with duration of ventilation prior to tracheostomy. Our
      objective was to associate timing of tracheostomy with clinical outcomes in PICU
      patients. DESIGN: This is a retrospective cohort study of patients undergoing
      tracheostomy. Patient factors and duration of ventilation prior to tracheostomy
      were collected on each patient. Morbidities such as ventilator-associated
      pneumonia, central catheter-associated bloodstream infection, and cardiopulmonary
      arrests were examined both pre- and posttracheostomy. ICU and total hospital
      length of stay as well as mortality were recorded. For data analysis regarding
      tracheostomy timing, patients were stratified into early and late groups using a
      cutoff of 14 days. SETTING: The PICUs and cardiac ICUs in a quaternary-care
      children's hospital. PATIENTS: All patients undergoing tracheostomy over a 3-year
      period. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients were analyzed with
      a median of 22 days of ventilation prior to tracheostomy. Patient factors
      associated with longer pretracheostomy ventilation included congenital heart
      disease and vasoactive drug use. Clinical events associated with longer
      pretracheostomy ventilation included bloodstream infection, ventilator-associated
      pneumonia, and cardiac arrest. Age, congenital heart disease, vasoactive drug
      use, bloodstream infection, and ventilator-associated pneumonia each
      independently increased pretracheostomy ventilator days. Median ICU length of
      stay after tracheostomy was 18 days. For each pretracheostomy ventilator day, ICU
      length of stay increased by 0.5 days and hospital length of stay increased by 1.9
      days. For patients undergoing early tracheostomy, ICU and total hospital lengths
      of stay were 4 days and 4 weeks shorter, respectively. CONCLUSIONS: Analysis of
      our results suggests that a longer duration of ventilation prior to tracheostomy
      is associated with increased ICU morbidities and length of stay. Early
      tracheostomy may have significant benefits without adversely affecting mortality.

PMID- 25581631
TI  - Progesterone for neuroprotection in pediatric traumatic brain injury.
AB  - OBJECTIVE: To provide an overview of the preclinical literature on progesterone
      for neuroprotection after traumatic brain injury and to describe unique features
      of developmental brain injury that should be considered when evaluating the
      therapeutic potential for progesterone treatment after pediatric traumatic brain
      injury. DATA SOURCES: National Library of Medicine PubMed literature review.
      STUDY SELECTION: The mechanisms of neuroprotection by progesterone are reviewed,
      and the preclinical literature using progesterone treatment in adult animal
      models of traumatic brain injury is summarized. Unique features of the developing
      brain that could either enhance or limit the efficacy of neuroprotection by
      progesterone are discussed, and the limited preclinical literature using
      progesterone after acute injury to the developing brain is described. Finally,
      the current status of clinical trials of progesterone for adult traumatic brain
      injury is reviewed. DATA EXTRACTION AND DATA SYNTHESIS: Progesterone is a
      pleiotropic agent with beneficial effects on secondary injury cascades that occur
      after traumatic brain injury, including cerebral edema, neuroinflammation,
      oxidative stress, and excitotoxicity. More than 40 studies have used progesterone
      for treatment after traumatic brain injury in adult animal models, with results
      summarized in tabular form. However, very few studies have evaluated progesterone
      in pediatric animal models of brain injury. To date, two human phase II trials of
      progesterone for adult traumatic brain injury have been published, and two
      multicenter phase III trials are underway. CONCLUSIONS: The unique features of
      the developing brain from that of a mature adult brain make it necessary to
      independently study progesterone in clinically relevant, immature animal models
      of traumatic brain injury. Additional preclinical studies could lead to the
      development of a novel neuroprotective therapy that could reduce the long-term
      disability in head-injured children and could potentially provide benefit in
      other forms of pediatric brain injury (global ischemia, stroke, and statue
      epilepticus).

PMID- 25581634
TI  - Antithrombin concentrates use in children on extracorporeal membrane oxygenation:
      a retrospective cohort study.
AB  - OBJECTIVE: To investigate whether receipt of any antithrombin concentrate
      improves laboratory and clinical outcomes in children undergoing extracorporeal
      membrane oxygenation for respiratory failure during their hospitalization
      compared with those who did not receive antithrombin. DESIGN: Retrospective
      cohort study. SETTING: Single, tertiary-care pediatric hospital. PATIENTS: Sixty
      four neonatal and pediatric patients who underwent extracorporeal membrane
      oxygenation for respiratory failure between January 2007 and September 2011.
      INTERVENTION: Exposure to any antithrombin concentrate during their
      extracorporeal membrane oxygenation course compared with similar children who
      never received antithrombin concentrate. MEASUREMENTS AND MAIN RESULTS: Thirty
      patients received at least one dose of antithrombin during their extracorporeal
      membrane oxygenation course and 34 patients did not receive any. The median age
      at admission was less than 1-month old. Age, duration of extracorporeal membrane
      oxygenation, or first antithrombin level did not differ significantly between the
      two cohorts. The mean plasma antithrombin level in those who never received
      antithrombin was 42.2% compared with 66% in those who received it. However, few
      levels reached the targeted antithrombin level of 120% and those who did fell
      back to deficient levels within an average of 6.8 hours. For those who received
      antithrombin concentrate, heparin infusion rates decreased by an average of 10.2
      U/kg/hr for at least 12 hours following administration. No statistical
      differences were noted in the number of extracorporeal membrane oxygenation
      circuit changes, in vivo clots or hemorrhages, transfusion requirements, hospital
      or ICU length of stay, or in-hospital mortality. CONCLUSIONS: Intermittent, on
      demand dosing of antithrombin concentrate in pediatric patients on extracorporeal
      membrane oxygenation for respiratory failure increased antithrombin levels, but
      not typically to the targeted level. Patients who received antithrombin
      concentrate also had decreased heparin requirements for at least 12 hours after
      dosing. However, no differences were noted in the measured clinical endpoints. A
      prospective, randomized study of this intervention may require different dosing
      strategies; such a study is warranted given the unproven efficacy of this costly
      product.

PMID- 25581635
TI  - Population pharmacokinetics analysis of AMG 416, an allosteric activator of the
      calcium-sensing receptor, in subjects with secondary hyperparathyroidism
      receiving hemodialysis.
AB  - This study characterizes the population pharmacokinetics of AMG 416, an
      allosteric activator of the calcium-sensing receptor, in subjects with secondary
      hyperparathyroidism receiving hemodialysis. AMG 416 doses ranging from 2.5 to 60
      mg were administered intravenously as single or multiple thrice weekly (TIW)
      doses at the end of hemodialysis during rinseback. The influence of demographics,
      concomitant medications, and other disease-related biomarkers on pharmacokinetic
      parameters was explored. The predictability of the final model was evaluated
      using bootstrapping and visual predictive checks. A 3-compartment linear
      pharmacokinetic model that accounts for the hemodialysis clearance best described
      the data. Plasma clearance (interindividual variability) was 0.564 L/h (14.0%CV).
      The hemodialysis clearance was 22.2 L/h. The volume of distribution at steady
      state was approximately 624 L (82%CV). The mean time to achieve 90% steady-state
      predialysis concentrations with 3- and 6-hour hemodialysis TIW was 46 and 32
      days, respectively. No statistically significant (P < .01) covariates effect was
      found on pharmacokinetic parameters. Bootstrapping and predictive checks
      supported model predictive ability. AMG 416 exhibits linear and stationary
      pharmacokinetics within the range of doses evaluated. Within the range of
      covariate values investigated, pharmacokinetically driven adjustments of AMG 416
      dosing on the basis of these covariates were not warranted. 

PMID- 25581638
TI  - Prompt immune tolerance induction at inhibitor diagnosis regardless of titre may
      increase overall success in haemophilia A complicated by inhibitors: experience
      of two U.S. centres.
AB  - Current guidelines recommend delaying the start of immune tolerance induction
      (ITI) until the inhibitor titre is <10 Bethesda units (BU) to improve success.
      This study was conducted to evaluate ITI outcome relative to time to start ITI
      from inhibitor detection irrespective of inhibitor titre. Data were
      retrospectively collected from two U.S. haemophilia treatment centres (HTCs) on
      subjects with severe/moderate factor VIII (FVIII) deficiency with inhibitors who
      underwent ITI. Outcomes were defined pragmatically: success--negative inhibitor
      titre and ability to use FVIII concentrate for treatment/bleed prevention;
      partial success--inhibitor titre 1 to <5 BU with ability to use FVIII concentrate
      for treatment of bleeding; failure--ITI ongoing >3 years without achieving
      success/partial success, or ITI discontinuation. Fifty-eight subjects were
      included; 32 of 39 (82%) with high-responding inhibitor (HRI) achieved success, 7
      failed. HRI subjects were subdivided based on ITI start time: 23/39 subjects
      started within 1 month of detection and 22/23 (96%) achieved success. Of these
      23, 13 started ITI with an inhibitor titre >=10 BU; all were successes. Eleven of
      39 HRI subjects had an interval >6 months until ITI start; 7 (64%) achieved
      success. Time from inhibitor detection to ITI start may play a critical role in
      outcome. A titre >=10 BU at ITI start did not influence outcome in subjects when
      ITI was initiated within 1 month of detection. Prompt ITI should be considered a
      viable therapeutic option in newly identified patients with inhibitors regardless
      of current inhibitor titre.

PMID- 25581639
TI  - Association between choroidal thickness and the response to intravitreal
      ranibizumab injection in age-related macular degeneration.
AB  - PURPOSE: To investigate the relationship between the choroidal thicknesses of
      eyes of patients with age-related macular degeneration (AMD) and the outcomes of
      intravitreal ranibizumab injection. METHODS: We reviewed the medical records of
      141 consecutive eyes (80 with typical neovascular AMD and 61 with polypoidal
      choroidal vasculopathy [PCV]) treated by intravitreal ranibizumab and 121 normal
      control eyes matched in terms of age and spherical equivalent (SE). Eyes of
      patients were divided into three subgroups with thin, medium and thick choroids.
      We investigated the relationships between choroidal thickness and treatment
      outcomes of intravitreal ranibizumab. RESULTS: In eyes with typical neovascular
      AMD, thin choroids were associated with older age (linear regression; p < 0.0001)
      and larger choroidal neovascularization (CNV) lesions (p = 0.049). Patients with
      thin choroids had a higher prevalence of intra-/subretinal fluid (generalized
      estimated equation; thin versus medium p < 0.0001; thin versus thick p = 0.003),
      and less visual gain from baseline to 12 months after treatment, than did other
      subgroups (linear mixed model; thin versus medium p < 0.0001; thin versus thick p
      = 0.023). PCV eyes with thick choroids more often had retinal fluid, and eyes
      with thin choroids experienced more frequent resolution of retinal fluid, from
      baseline to 12 months after treatment (thick versus medium p < 0.0001, thick
      versus thin p < 0.0001, thin versus medium p = 0.001). No intergroup difference
      in post-treatment functional outcome was noted in eyes with PCV (p = 0.584).
      CONCLUSIONS: Subfoveal choroidal thickness was associated with functional and
      anatomical outcomes after intravitreal ranibizumab injection in eyes with typical
      neovascular AMD and PCV.

PMID- 25581641
TI  - Enhancing Phytoremediation Potential of Pennisetum clandestinum Hochst in Cadmium
      Contaminated Soil Using Smoke-Water and Smoke-Isolated Karrikinolide.
AB  - The use of plant growth regulators (PGRs) and biostimulants to enhance
      phytoextraction is gaining popularity in phytoremediation technology. This study
      investigated the stimulatory effects of smoke-water (SW), a smoke-derived
      compound karrikinolide (KAR1) and other known plant growth regulators (PGRs)
      [gibberellic acid (GA3), kinetin (Kin) and indole-3-butyric acid (IBA)] to
      enhance the phytoextraction potential of Pennisetum clandestinum. Pennisetum
      clandestinum seedlings were grown for 10 weeks in vermiculite using Hoagland's
      nutrient solution and were treated with cadmium (Cd) (2, 5, and 10 mg L(-1)) and
      SW, KAR1 and PGRs. KAR1 exhibited positive effects on shoot and root dry weight
      (140 and 137 mg respectively) at the highest concentration of Cd (10 mg L(-1))
      compared to all the other treatments. KAR1 and SW treatments used in the present
      study significantly improved the phytoextraction potential of P. clandestinum
      (602 and 575 mg kg(-1) respectively) compared to the other tested PGRs. This is
      the first report on the use of SW and KAR1 to enhance phytoremediation potential
      in P. clandestinum. Further studies are needed to elucidate the exact mechanisms
      of smoke constituents involved in phytoextraction potential of plant species.

PMID- 25581640
TI  - Muscle microvascular blood flow responses in insulin resistance and ageing.
AB  - Insulin resistance plays a key role in the development of type 2 diabetes.
      Skeletal muscle is the major storage site for glucose following a meal and as
      such has a key role in maintenance of blood glucose concentrations. Insulin
      resistance is characterised by impaired insulin-mediated glucose disposal in
      skeletal muscle. Multiple mechanisms can contribute to development of muscle
      insulin resistance and our research has demonstrated an important role for loss
      of microvascular function within skeletal muscle. We have shown that insulin can
      enhance blood flow to the microvasculature in muscle thus improving the access of
      glucose and insulin to the myocytes to augment glucose disposal. Obesity, insulin
      resistance and ageing are all associated with impaired microvascular responses to
      insulin in skeletal muscle. Impairments in insulin-mediated microvascular
      perfusion in muscle can directly cause insulin resistance, and this event can
      occur early in the aetiology of this condition. Understanding the mechanisms
      involved in the loss of microvascular function in muscle has the potential to
      identify novel treatment strategies to prevent or delay progression of insulin
      resistance and type 2 diabetes. 

PMID- 25581643
TI  - In memory of James D. Beard 7-21-1937 to 10-7-2014.

PMID- 25581642
TI  - Quantitative toxicoproteomic analysis of zebrafish embryos exposed to a retinoid
      X receptor antagonist UVI3003.
AB  - Retinoid X receptor (RXR) antagonists, including some environmental endocrine
      disruptors, have a teratogenic effect on vertebrate embryos. To investigate the
      toxicological mechanism on the protein expression level, a quantitative proteomic
      study was conducted to analyze the proteome alterations of zebrafish (Danio
      rerio) embryos exposed to gradient concentrations of a representative RXR
      antagonist UVI3003. Using isobaric Tags for Relative and Absolute Quantitation
      (iTRAQ) labeling coupled nano high-performance liquid chromatography-tandem mass
      spectrometry (nano HPLC-MS/MS), in total 6592 proteins were identified, among
      which 195 proteins were found to be differentially expressed by more than a two
      fold change in exposed groups compared with the control. Gene ontology analysis
      showed that these differential proteins were mostly involved in anatomical
      structure development, biosynthetic process, ion binding and oxidoreductase
      activity. Moreover, the biological pathways of translation, lipoprotein
      metabolism, cell survival and gluconeogenesis were intensively inhibited after
      exposure. Some significantly downregulated proteins such as apolipoprotein A-I
      and vitellogenin and upregulated proteins such as calcium activated nucleotidase
      1b, glutathione S-transferase and glucose 6-dehydrogenases showed a strong dose
      dependent response. The results provided new insight into the molecular details
      of RXR antagonist-induced teratogenicity and added novel information of pathways
      and potential biomarkers for evaluation of RXR interfering activity.

PMID- 25581644
TI  - Alcohol marketing and underage drinking: time to get real.

PMID- 25581645
TI  - To drink or not to drink: that is the question.

PMID- 25581646
TI  - Physicians' prescription for lifetime abstainers aged 40 to 50 to take a drink a
      day is not yet justified.

PMID- 25581647
TI  - N-acetylcysteine inhibits the up-regulation of mitochondrial biogenesis genes in
      livers from rats fed ethanol chronically.
AB  - BACKGROUND: Chronic ethanol (EtOH) administration to experimental animals induces
      hepatic oxidative stress and up-regulates mitochondrial biogenesis. The
      mechanisms by which chronic EtOH up-regulates mitochondrial biogenesis have not
      been fully explored. In this work, we hypothesized that oxidative stress is a
      factor that triggers mitochondrial biogenesis after chronic EtOH feeding. If our
      hypothesis is correct, co-administration of antioxidants should prevent up
      regulation of mitochondrial biogenesis genes. METHODS: Rats were fed an EtOH
      containing diet intragastrically by total enteral nutrition for 150 days, in the
      absence or presence of the antioxidant N-acetylcysteine (NAC) at 1.7 g/kg/d;
      control rats were administered isocaloric diets where carbohydrates substituted
      for EtOH calories. RESULTS: EtOH administration significantly increased hepatic
      oxidative stress, evidenced as decreased liver total glutathione and reduced
      glutathione/glutathione disulfide ratio. These effects were inhibited by co
      administration of EtOH and NAC. Chronic EtOH increased the expression of
      mitochondrial biogenesis genes including peroxisome proliferator-activated
      receptor gamma-coactivator-1 alpha and mitochondrial transcription factor A, and
      mitochondrial DNA; co-administration of EtOH and NAC prevented these effects.
      Chronic EtOH administration was associated with decreased mitochondrial mass,
      inactivation and depletion of mitochondrial complex I and complex IV, and
      increased hepatic mitochondrial oxidative damage, effects that were not prevented
      by NAC. CONCLUSIONS: These results suggest that oxidative stress caused by
      chronic EtOH triggered the up-regulation of mitochondrial biogenesis genes in rat
      liver, because an antioxidant such as NAC prevented both effects. Because NAC did
      not prevent liver mitochondrial oxidative damage, extra-mitochondrial effects of
      reactive oxygen species may regulate mitochondrial biogenesis. In spite of the
      induction of hepatic mitochondrial biogenesis genes by chronic EtOH,
      mitochondrial mass and function decreased probably in association with
      mitochondrial oxidative damage. These results also predict that the effectiveness
      of NAC as an antioxidant therapy for chronic alcoholism will be limited by its
      limited antioxidant effects in mitochondria, and its inhibitory effect on
      mitochondrial biogenesis.

PMID- 25581648
TI  - Dual-trait selection for ethanol consumption and withdrawal: genetic and
      transcriptional network effects.
AB  - BACKGROUND: Data from C57BL/6J (B6) * DBA/2J (D2) F2 intercrosses (B6xD2 F2 ),
      standard and recombinant inbred strains, and heterogeneous stock mice indicate
      that a reciprocal (or inverse) genetic relationship exists between alcohol
      consumption and withdrawal severity. Furthermore, some genetic studies have
      detected reciprocal quantitative trait loci (QTLs) for these traits. We used a
      novel mouse model developed by simultaneous selection for both high alcohol
      consumption/low withdrawal and low alcohol consumption/high withdrawal and
      analyzed the gene expression and genome-wide genotypic differences. METHODS:
      Randomly chosen third selected generation (S3 ) mice (N = 24/sex/line), bred from
      a B6xD2 F2 , were genotyped using the Mouse Universal Genotyping Array, which
      provided 2,760 informative markers. QTL analysis used a marker-by-marker strategy
      with the threshold for a significant log of the odds (LOD) set at 10. Gene
      expression in the ventral striatum was measured using the Illumina Mouse 8.2
      array. Differential gene expression and the weighted gene co-expression network
      analysis (WGCNA) were implemented. RESULTS: Significant QTLs for
      consumption/withdrawal were detected on chromosomes (Chr) 2, 4, 9, and 12. A
      suggestive QTL mapped to Chr 6. Some of the QTLs overlapped with known QTLs
      mapped for 1 of the traits individually. One thousand seven hundred and forty
      five transcripts were detected as being differentially expressed between the
      lines; there was some overlap with known withdrawal genes (e.g., Mpdz) located
      within QTL regions. WGCNA revealed several modules of co-expressed genes showing
      significant effects in both differential expression and intramodular
      connectivity; a module richly annotated with kinase-related annotations was most
      affected. CONCLUSIONS: Marked effects of selection on expression and network
      structure were detected. QTLs overlapping with differentially expressed genes on
      Chr 2 (distal) and 4 suggest that these are cis-eQTLs (Chr 2: Kif3b, Kcnq2; Chr
      4: Mpdz, Snapc3). Other QTLs identified were on Chr 2 (proximal), 9, and 12.
      Network results point to involvement of kinase-related mechanisms and outline the
      need for further efforts such as interrogation of noncoding RNAs.

PMID- 25581649
TI  - Moderate-level prenatal alcohol exposure induces sex differences in dopamine d1
      receptor binding in adult rhesus monkeys.
AB  - BACKGROUND: We examined the effects of moderate prenatal alcohol exposure and/or
      prenatal stress exposure on (D1 R) binding in a non human primate model. The
      dopamine D1 R is involved in executive function, and it may play a role in
      cognitive behavioral deficits associated with prenatal alcohol and/or stress
      exposure. Little is known, however, about the effects of prenatal alcohol and/or
      stress exposure on the D1 R. We expected that prenatal insults would lead to
      alterations in D1 R binding in prefrontal cortex (PFC) and striatum in adulthood.
      METHODS: Rhesus macaque females were randomly assigned to moderate alcohol
      exposure and/or mild prenatal stress as well as a control condition during
      pregnancy. Thirty-eight offspring were raised identically and studied as adults
      by noninvasive in vivo neuroimaging using positron emission tomography with the
      D1 antagonist radiotracer [(11) C]SCH 23390. Radiotracer binding in PFC and
      striatum was evaluated by 2 (alcohol) * 2 (stress) * 2 (sex) analysis of
      variance. RESULTS: In PFC, a significant alcohol * sex interaction was observed
      with prenatal alcohol exposure leading to increased [(11) C]SCH 23390 binding in
      male monkeys. No main effect of prenatal alcohol or prenatal stress exposure was
      observed. CONCLUSIONS: These results suggest that prenatal alcohol exposure
      results in long-term increases in prefrontal dopamine D1 R binding in males. This
      may help explain gender differences in the prevalence of neurodevelopmental
      disorders consequent to prenatal alcohol exposure.

PMID- 25581650
TI  - Effects of prenatal alcohol and cigarette exposure on offspring substance use in
      multiplex, alcohol-dependent families.
AB  - BACKGROUND: Prenatal exposures to alcohol, cigarettes, and other drugs of abuse
      are associated with numerous adverse consequences for affected offspring,
      including increased risk for substance use and abuse. However, maternal substance
      use during pregnancy appears to occur more often in those with a family history
      of alcohol dependence. Utilizing a sample that is enriched for familial alcohol
      dependence and includes controls selected for virtual absence of familial alcohol
      dependence could provide important information on the relative contribution of
      familial risk and prenatal exposures to offspring substance use. METHODS: A
      sample of multigenerational families specifically ascertained to be at either
      high or low risk for developing alcohol dependence (AD) provided biological
      offspring for a longitudinal prospective study. High-risk families were selected
      based on the presence of 2 alcohol-dependent sisters. Low-risk families were
      selected on the basis of minimal first and second-degree relatives with AD. High
      risk (HR = 99) and Low-risk offspring (LR = 110) were assessed annually during
      childhood and biennially in young adulthood regarding their alcohol, drug, and
      cigarette use. At the first childhood visit, mothers were interviewed concerning
      their prenatal use of substances. RESULTS: High-risk mothers were more likely to
      use alcohol, cigarettes, and other drugs during pregnancy than low-risk control
      mothers, and to consume these substances in greater quantities. Across the
      sample, prenatal exposure to alcohol was associated with increased risk for both
      offspring cigarette use and substance use disorders (SUD), and prenatal cigarette
      exposure was associated with increased risk for offspring cigarette use.
      Controlling for risk status by examining patterns within the HR sample, prenatal
      cigarette exposure remained a specific predictor of offspring cigarette use, and
      prenatal alcohol exposure was specifically associated with increased risk for
      offspring SUD. CONCLUSIONS: Women with a family history of SUD are at increased
      risk for substance use during pregnancy. Both familial loading for alcohol
      dependence and prenatal exposure to alcohol or cigarettes are important risk
      factors in the development of offspring substance use. An inadequate assessment
      of family history may obscure important interactions between familial risk and
      prenatal exposures on offspring outcomes.

PMID- 25581651
TI  - Prenatal ethanol exposure impairs executive function in mice into adulthood.
AB  - BACKGROUND: Despite evidence that prenatal alcohol exposure (PAE) can lead to a
      wide range of impairments in cognitive, social, and emotional behaviors, drinking
      during pregnancy remains common. Although there is a general understanding that
      high levels of drinking during pregnancy are unsafe, conflicting evidence
      regarding the impact of low intake may account for the persistence of this
      behavior. METHODS: To investigate the effects of PAE on learning and executive
      control, we utilized a voluntary paradigm where pregnant mice had access to a
      saccharin-sweetened 10% alcohol solution for 4 hours, during the dark cycle,
      throughout gestation. Male and female offspring were tested as adults on a touch
      screen discrimination and reversal task mediated by corticostriatal circuits.
      RESULTS: Consistent with previous findings, PAE did not lead to gross
      morphological, motor, or sensory alterations in offspring. Both PAE and saccharin
      control female mice were slower to acquire the discrimination than males, but PAE
      did not impair associative learning in either sex. During reversal, PAE led to a
      specific and significant impairment in the early phase, where cortical control is
      most required to flexibly alter choice behavior. PAE mice showed a significant
      increase in maladaptive perseverative responses but showed intact learning of the
      new association during late reversal. CONCLUSIONS: Previously, data from clinical
      studies have suggested that executive control deficits may underlie cognitive, as
      well as social, problems seen in adolescents with documented PAE. These data
      demonstrate that even more moderate alcohol exposure during development can lead
      to impaired cognitive functioning well into adulthood.

PMID- 25581652
TI  - Ethanol reduces evoked dopamine release and slows clearance in the rat medial
      prefrontal cortex.
AB  - BACKGROUND: Ethanol (EtOH) intoxication affects cognitive performance,
      contributing to attentional deficits and poor decision making, which may occur
      via actions in the medial prefrontal cortex (mPFC). mPFC function is modulated by
      the catecholamines dopamine and norepinephrine. In this study, we examine the
      acute effects of EtOH on electrically evoked dopamine release and clearance in
      the mPFC of anesthetized rats naive to alcohol or chronically exposed to alcohol
      during adolescence. METHODS: Dopamine release and clearance was evoked by
      electrical stimulation of the ventral tegmental area (VTA) and measured in the
      mPFC of anesthetized rats with fast-scan cyclic voltammetry. In Experiments 1 and
      2, effects of a high dose of EtOH (4 g/kg, intraperitoneally) on dopamine
      neurotransmission in the mPFC of EtOH-naive rats and rats given EtOH exposure
      during adolescence were investigated. Effects of cumulative dosing of EtOH (0.5
      to 4 g/kg) on the dopamine release and clearance were investigated in Experiment
      3. Experiment 4 studied effects of EtOH locally applied to the VTA on the
      dopamine neurotransmission in the mPFC of EtOH-naive rats. RESULTS: A high dose
      of EtOH decreased evoked dopamine release within 10 minutes of administration in
      EtOH-naive rats. When tested via cumulative dosing from 0.5 to 4 g/kg, both 2 and
      4 g/kg EtOH inhibited evoked dopamine release in the mPFC of EtOH-naive rats,
      while 4 g/kg EtOH also slowed dopamine clearance. A similar effect on
      electrically evoked dopamine release in the mPFC was observed after infusion of
      EtOH into the VTA. Interestingly, intermittent EtOH exposure during adolescence
      had no effect on observed changes in mPFC dopamine release and clearance induced
      by acute EtOH administration. CONCLUSIONS: Taken together, these data describe
      EtOH-induced reductions in the dynamics of VTA-evoked mPFC dopamine release and
      clearance, with the VTA contributing to the attenuation of evoked mPFC dopamine
      release induced by EtOH.

PMID- 25581653
TI  - Protective effects of hypothalamic beta-endorphin neurons against alcohol-induced
      liver injuries and liver cancers in rat animal models.
AB  - BACKGROUND: Recently, retrograde tracing has provided evidence for an influence
      of hypothalamic beta-endorphin (BEP) neurons on the liver, but functions of these
      neurons are not known. We evaluated the effect of BEP neuronal activation on
      alcohol-induced liver injury and hepatocellular cancer. METHODS: Male rats
      received either BEP neuron transplants or control transplants in the hypothalamus
      and were randomly assigned to feeding alcohol-containing liquid diet or control
      liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN).
      Liver tissues of these animals were analyzed histochemically and biochemically
      for tissue injuries or cancer. RESULTS: Alcohol feeding increased liver weight
      and induced several histopathological changes such as prominent microvesicular
      steatosis and hepatic fibrosis. Alcohol feeding also increased the levels of
      triglyceride, hepatic stellate cell (HSC) activation factors, and catecholamines
      in the liver and endotoxin levels in the plasma. However, these effects of
      alcohol on the liver were reduced in animals with BEP neuron transplants. BEP
      neuron transplants also suppressed carcinogen-induced liver histopathologies such
      as extensive fibrosis, large focus of inflammatory infiltration, hepatocellular
      carcinoma (HCC), collagen deposition, numbers of preneoplastic foci, levels of
      HSC activation factors and catecholamines, as well as inflammatory milieu and
      increased the levels of natural killer cell cytotoxic factors in the liver.
      CONCLUSIONS: These findings are the first evidence for a role of hypothalamic BEP
      neurons in influencing liver functions. Additionally, the data identify that BEP
      neuron transplantation prevents hepatocellular injury and HCC formation possibly
      via influencing the immune function.

PMID- 25581655
TI  - Characteristics of women who consume alcohol before and after pregnancy
      recognition in a Canadian sample: a prospective cohort study.
AB  - BACKGROUND: High levels of alcohol consumption during pregnancy are teratogenic
      to fetal development, yet less is known about the effects of low levels of
      consumption. Only a few studies have reported on the predictors and maternal
      characteristics associated with different alcohol consumption patterns prior to
      and following pregnancy recognition. METHODS: The All Our Babies longitudinal
      study in Alberta, Canada was used to analyze the association of maternal
      characteristics with binge drinking prior to pregnancy recognition and low to
      moderate levels after pregnancy recognition among 2,246 women who consumed
      alcohol 1 year prior to pregnancy. Bivariate and multivariable analyses were
      conducted. RESULTS: Thirteen percent of women reported binge drinking prior to
      pregnancy recognition. Forty-six percent reported drinking after pregnancy
      recognition, almost all at low to moderate levels. Significant, independent
      predictors (odds ratio, 95% confidence interval) of binge drinking in early
      pregnancy included high school or less education (3.61, 1.81 to 7.19), some or
      completed university/college (2.23, 1.16 to 4.27), nulliparity (1.62, 1.19,
      2.20), not trying to get pregnant (1.92, 1.37 to 2.69), smoked in the year prior
      to pregnancy (1.98, 1.43 to 2.73), binge drinking in the year prior to pregnancy
      (10.83, 6.71 to 17.46), and low dispositional optimism (1.73, 1.23 to 2.42).
      Independent predictors of low to moderate average levels of consumption after
      pregnancy recognition included not trying to get pregnant (1.91, 1.45 to 2.52),
      prepregnancy body mass index <25.0 kg/m(2) (1.41, 1.61 to 1.72), smoking in the
      year before pregnancy (1.90, 1.43 to 2.53), and binge drinking in the year before
      pregnancy (2.62, 2.16 to 3.18). CONCLUSIONS: Common risk factors for different
      alcohol consumption patterns are unintended pregnancy and substance use behaviors
      prior to pregnancy. Other risk factors were specific to the different patterns.
      Targeted strategies that address the needs of alcohol or nicotine using women and
      that can reduce the risk of unintended pregnancy may be beneficial.

PMID- 25581654
TI  - Social cognition deficits and associations with drinking history in alcoholic men
      and women.
AB  - BACKGROUND: Previous studies have demonstrated the presence of a social cognition
      factor as an element of general cognition in healthy control and clinical
      populations. Recently developed measures of social cognition include the social
      perception and faces subtests of the Wechsler Advanced Clinical Solutions (ACS)
      Social Cognition module. While these measures have been validated on various
      clinical samples, they have not been studied in alcoholics. Alcoholism has been
      associated with emotional abnormalities and diminished social cognitive
      functioning as well as neuropathology of brain areas underlying social processing
      abilities. We used the ACS Social Perception and Faces subtests to assess
      alcoholism-related impairments in social cognition. METHODS: Social cognitive
      functioning was assessed in 77 abstinent alcoholic individuals (37 women) and 59
      nonalcoholic control participants (29 women), using measures of the ACS Social
      Cognition module and subtests of the Wechsler Adult Intelligence Scale-Fourth
      Edition (WAIS-IV) that contain a social cognition component (Picture Completion
      and Comprehension). Group and gender differences in ACS and WAIS-IV performance
      were assessed, as well as relationships between measures of alcoholism severity
      and social cognitive functioning. RESULTS: Alcoholics performed significantly
      worse than nonalcoholics on the ACS measures of Affect Naming and Faces Content.
      Alcoholic men were impaired relative to alcoholic women on Prosody Face Matching
      and Faces Content scores. Among alcoholics, longer durations of heavy drinking
      were associated with poorer performance on Affect Naming, and a greater number of
      daily drinks were associated with lower Prosody Face Matching performance. For
      alcoholic women, a longer duration of abstinence was associated with better
      performance on Affect Naming. CONCLUSIONS: Alcoholic men and women showed
      different patterns of associations between alcoholism indices and clinically
      validated social cognition assessments. These findings extend into the social
      cognition domain, previous literature demonstrating the presence of cognitive
      deficits in alcoholism, their association with alcoholism severity, and
      variability by gender. Moreover, because impairments in social cognition can
      persist despite extended abstinence, they have important implications for relapse
      prevention.

PMID- 25581656
TI  - Posttreatment effects of topiramate treatment for heavy drinking.
AB  - BACKGROUND: We examined whether the effects of topiramate and a single nucleotide
      polymorphism (rs2832407) in GRIK1, which encodes a kainate receptor subunit,
      persisted following a 12-week, placebo-controlled trial in 138 heavy drinkers
      with a treatment goal of reduced drinking. During treatment, topiramate 200 mg/d
      significantly reduced heavy drinking days and increased the frequency of
      abstinent days (Am J Psychiatry, 2014, 171:445). In the European-American (EA)
      subsample (n = 122), rs2832407 moderated the treatment effect on heavy drinking.
      METHODS: Patients were re-interviewed 3 and 6 months after the end of treatment.
      During treatment, we obtained 92.4% of drinking data, with 89.1 and 85.5%
      complete data at the 3- and 6-month follow-up visits, respectively. We examined 4
      outcomes over time in the overall sample and the EA subsample: percent heavy
      drinking days (PHDD), percent days abstinent (PDA), serum gamma-glutamyl
      transpeptidase (GGTP) concentration, and a measure of alcohol-related problems.
      RESULTS: In the full sample, the lower PHDD and higher PDA seen with topiramate
      treatment were no longer significant during follow-up. Nonetheless, the
      topiramate-treated patients had lower alcohol-related problem scores during
      treatment and both follow-up periods. Further, in the EA subsample, the greater
      reduction in PHDD seen with topiramate treatment in rs2832407*C-allele
      homozygotes persisted throughout follow-up, with no significant effects in A
      allele carriers. A reduction in GGTP concentration was consistent with the
      reduction in heavy drinking, but did not reach statistical significance.
      CONCLUSIONS: There are persistent therapeutic effects of topiramate in heavy
      drinkers, principally in rs2832407*C-allele homozygotes.

PMID- 25581657
TI  - Effects of naltrexone on neural and subjective response to alcohol in treatment
      seeking alcohol-dependent patients.
AB  - BACKGROUND: Positively reinforcing properties of alcohol are in part mediated by
      activation of the ventral striatum (VS). Alcohol-induced release of endogenous
      opioids is thought to contribute to this response. Preclinical studies show that
      the opioid antagonist naltrexone (NTX) can block this cascade, but its ability to
      do so in treatment-seeking alcoholics has not been examined. Our objective was to
      study the effects of NTX on alcohol-induced VS activation and on amygdala
      response to affective stimuli in treatment-seeking alcohol-dependent inpatients.
      METHODS: Sixty-three treatment-seeking alcoholics were randomized to receive NTX
      (50 mg) or placebo (PLC) daily. On Day 7, participants underwent an alcohol cue
      reactivity session, and craving was measured using the Penn Alcohol Craving
      Scale. On Day 9, participants received a saline infusion followed by an alcohol
      infusion and also viewed affective stimuli in a magnetic resonance scanner.
      RESULTS: Irrespective of medication treatment condition, the alcohol infusion did
      not activate the VS in the alcohol-dependent patients. Unexpectedly, VS
      activation was greater in NTX treated patients than in the PLC group. NTX treated
      patients also reported increased craving in response to alcohol cue exposure, and
      increased subjective response to alcohol ("high" and "intoxicated") compared to
      PLC subjects. No significant effects of alcohol infusion on brain response to
      affective stimuli were in the NTX or PLC groups. CONCLUSIONS: Unlike previous
      findings in social drinkers, a moderate level of intoxication did not activate
      the VS in treatment-seeking alcoholics. This is likely to reflect tolerance to
      the positively reinforcing properties of alcohol in this clinical population. Our
      findings may help explain the efficacy of NTX to reduce heavy drinking, but not
      to maintain abstinence.

PMID- 25581658
TI  - Effects of varenicline on ethanol-induced conditioned place preference, locomotor
      stimulation, and sensitization.
AB  - BACKGROUND: Varenicline, a partial nicotinic acetylcholine receptor (nAChR)
      agonist, is a promising new drug for the treatment of alcohol (ethanol [EtOH])
      dependence. Varenicline has been approved by the Food and Drug Administration as
      a smoking cessation therapeutic and has also been found to reduce EtOH
      consumption in humans and animal models of alcohol use. These studies examined
      the hypotheses that varenicline attenuates the stimulant and sensitizing effects
      of EtOH and reduces the motivational effects of EtOH-associated cues. The goal
      was to determine whether these effects of varenicline contribute to its
      pharmacotherapeutic effects for alcohol dependence. In addition, effects of
      varenicline on acute stimulation and/or on the acquisition of sensitization would
      suggest a role for nAChR involvement in these effects of EtOH. METHODS: Dose
      dependent effects of varenicline on the expression of EtOH-induced conditioned
      place preference (CPP), locomotor activation, and behavioral sensitization were
      examined. These measures model motivational effects of EtOH-associated cues,
      euphoric or stimulatory effects of EtOH, and EtOH-induced neuroadaptation. All
      studies used DBA/2J mice, an inbred strain with high sensitivity to these EtOH
      related effects. RESULTS: Varenicline did not significantly attenuate the
      expression of EtOH-induced CPP. Varenicline reduced locomotor activity and had
      the most pronounced effect in the presence of EtOH, with the largest effect on
      acute EtOH-induced locomotor stimulation and a trend for varenicline to attenuate
      the expression of EtOH-induced sensitization. CONCLUSIONS: Because varenicline
      did not attenuate the expression of EtOH-induced CPP, it may not be effective at
      reducing the motivational effects of EtOH-associated cues. This outcome suggests
      that reductions in the motivational effects of EtOH-associated cues may not be
      involved in how varenicline reduces EtOH consumption. However, varenicline did
      have effects on locomotor behavior and significantly attenuated acute EtOH
      induced locomotor stimulation. In humans who drink while taking varenicline, it
      might similarly reduce stimulant responses and have an impact on continued
      drinking. General sedative effects in such individuals should be carefully
      considered.

PMID- 25581659
TI  - Ethnic drinking cultures, gender, and socioeconomic status in Asian American and
      Latino drinking.
AB  - BACKGROUND: Heterogeneity in drinking across national groups is well documented,
      but what explains such heterogeneity is less clear. To improve understanding of
      the underlying cultural conditions that may lead to diverse drinking outcomes, we
      investigate whether 3 dimensions of ethnic drinking culture (EDC)-alcohol
      consumption level, drinking prevalence, and detrimental drinking pattern (DDP) in
      the country of origin (COO)-are significantly associated with alcohol consumption
      in Asian Americans and Latina/os, and whether the associations vary by gender and
      socioeconomic status (SES) as assessed by educational level. METHODS: A
      nationally representative sample of 1,012 Asian American and 4,831 Latino adults
      extracted from the Wave 2 National Epidemiologic Survey on Alcohol and Related
      Conditions data was used. A series of multiple logistic and linear regression
      models were fitted separately for Asian Americans and for Latinos. Analyses were
      also stratified by gender and educational level. RESULTS: Overall, the
      associations between EDC variables and drinking outcomes were more pronounced for
      all Asian Americans than for all Latina/os, for males than for females among
      Asian Americans, and for Latinas than for Latinos. In analyses simultaneously
      stratifying on gender and education level, however, there was a clear pattern of
      COO DDP associated with heavier drinking and alcohol consumption volume only for
      Latinos without a college degree. CONCLUSIONS: Ethnic drinking cultures may
      influence drinking in Asian American and Latino subgroups, albeit to a varying
      degree. Low-SES Latinos may be at disproportionate risk of harmful drinking
      patterns pervasive in their COO. Future research might investigate the complex
      interplay between socioeconomic disadvantage and cultural conditions to inform
      targeted interventions for subgroups at high risk of alcohol-related harms.

PMID- 25581662
TI  - Nutritional optic neuropathy in patients hospitalized for alcohol withdrawal.

PMID- 25581660
TI  - Perceived medical risks of drinking, alcohol consumption, and hepatitis C status
      among heavily drinking HIV primary care patients.
AB  - BACKGROUND: Heavy drinking poses significant risks to the health and survival of
      individuals infected with HIV, particularly those coinfected with hepatitis C
      virus (HCV). However, little is known about patients' perceptions of these risks,
      and whether these perceptions relate to their alcohol consumption. METHODS: A
      sample of 254 heavily drinking HIV primary care patients (78% male; 94.5%
      minority; 31.8% with HCV) reported on their perceptions of the medical risks of
      drinking and on their alcohol consumption prior to participation in a drinking
      reduction intervention trial. RESULTS: In the HIV-infected sample as a whole,
      62.9% reported that they had a medical problem made worse by drinking, and 64.3%
      reported restricting drinking to avoid future medical problems. Although patients
      coinfected with HIV/HCV reported greater efforts to restrict drinking to avoid
      future medical problems (adjusted odds ratio = 1.94), their reported drinking
      quantity and frequency did not differ from that of HIV mono-infected patients.
      Awareness of medical risk was not associated with drinking level. Effort to
      restrict drinking to avoid medical risk was associated with lower drinking
      quantity, frequency, and binge frequency (ps < 0.05), but the association with
      binge frequency was specific to patients without HCV. CONCLUSIONS: Over one-third
      of HIV patients are unaware of the medical risks of drinking, and do not restrict
      use, suggesting the need for intervention in this group. Patients coinfected with
      HIV/HCV may report more effort to restrict drinking, but their reported drinking
      quantity and frequency suggest that they are actually drinking just as heavily as
      HIV mono-infected patients. Awareness of medical risk was unrelated to drinking,
      which suggests the need for interventions consisting of more than simple
      education. However, reported effort to restrict drinking did predict less
      drinking, suggesting the importance of patient commitment and initiative in
      change.

PMID- 25581661
TI  - Adjustments for drink size and ethanol content: new results from a self-report
      diary and transdermal sensor validation study.
AB  - BACKGROUND: Prior studies adjusting self-reported measures of alcohol intake for
      drink size and ethanol (EtOH) content have relied on single-point assessments.
      METHODS: A prospective 28-day diary study investigated magnitudes of drink-EtOH
      adjustments and factors associated with these adjustments. Transdermal alcohol
      sensor (TAS) readings and prediction of alcohol-related problems by number of
      drinks versus EtOH-adjusted intake were used to validate drink-EtOH adjustments.
      Self-completed event diaries listed up to 4 beverage types and 4 drinking
      events/d. Eligible volunteers had >= weekly drinking and >=3+ drinks per occasion
      with >=26 reported days and pre- and postsummary measures (n = 220). Event
      reports included drink types, sizes, brands or spirits contents, venues, drinks
      consumed, and drinking duration. RESULTS: Wine drinks averaged 1.19, beer 1.09,
      and spirits 1.54 U.S. standard drinks (14 g EtOH). Mean-adjusted alcohol intake
      was 22% larger using drink size and strength (brand/EtOH concentration) data.
      Adjusted drink levels were larger than "raw" drinks in all quantity ranges.
      Individual-level drink-EtOH adjustment ratios (EtOH adjusted/unadjusted amounts)
      averaged across all days drinking ranged from 0.73 to 3.33 (mean 1.22).
      Adjustment ratio was only marginally (and not significantly) positively related
      to usual quantity, frequency, and heavy drinking (all ps < 0.10), independent of
      gender, age, employment, and education, but those with lower incomes (both p <
      0.01) drank stronger/bigger drinks. Controlling for raw number of drinks and
      other covariates, degree of adjustment independently predicted alcohol dependence
      symptoms (p < 0.01) and number of consequences (p < 0.05). In 30 respondents with
      sufficiently high-quality TAS readings, higher correlations (p = 0.04) were found
      between the adjusted versus the raw drinks/event and TAS areas under the curve.
      CONCLUSIONS: Absent drink size and strength data, intake assessments are downward
      biased by at least 20%. Between-subject variation in typical drink content and
      pour sizes should be addressed in treatment and epidemiological research.

PMID- 25581663
TI  - Effects of wall shear stress in venous neointimal hyperplasia of arteriovenous
      fistulae.
AB  - AIM: An arteriovenous fistulae (AVF) is the preferred vascular access for
      maintenance haemodialysis patients. Its dysfunction is often due to venous
      stenosis, which is mainly caused by neointimal hyperplasia. Additionally,
      haemodynamic forces, especially wall shear stress (WSS), as a mechanical stimuli
      to venous wall have a significant role in neointimal hyperplasia. The purpose of
      this study was to evaluate the association between WSS and neointimal
      hyperplasia. METHODS: An 'end-to-side' AVF was created between the right femoral
      artery and vein of canines. Canines were killed at 7 and 28 days post-surgery.
      The velocity and WSS in the three-dimensional computational model of AVF were
      simulated using computational fluid dynamics (CFDs). The four typical sites of
      the vein evaluated in this study, chosen according to the haemodynamic analysis,
      included the arteriovenous anastomosis (A-V), the juxta-anastomotic segment (J
      V), the juxta-ligation segment (L-V) and the proximal vein (P-V). The specimens
      were haematoxylin-eosin stained and the intima-media thickening was then
      measured. RESULTS: Neointimal hyperplasia was more obvious in the inner wall of
      the J-V and L-V (low-and-disturbed WSS) sites compared with the P-V and A-V
      sites, and the outer wall of the L-V and J-V segments (high or laminar WSS) (P <
      0.01). CONCLUSION: In this study, we described the haemodynamic condition in the
      AVF and found that neointimal hyperplasia predisposed to occur in the inner wall
      of venous segment near the anastomosis. We also found that not only the
      neointimal hyperplasia has a strong inverse correlation with WSS levels, but also
      is related to flow patterns.

PMID- 25581665
TI  - Formaldehyde.
AB  - Formaldehyde is the American Contact Dermatitis Society Contact Allergen of the
      Year for 2015. The exposure is widespread, and contact allergy might be difficult
      to suspect in the individual dermatitis patient. The relevance of contact allergy
      to formaldehyde might also be difficult to evaluate. Recently, however, several
      studies have been performed aimed at enhancing the patch test technique and
      evaluating the clinical relevance of contact allergy to formaldehyde. The patch
      test concentration of formaldehyde has been recommended by the European
      Environmental Contact Dermatitis Research Group to be 2.0%, that is, the dose of
      0.60 mg/cm (wt/vol) instead of 1.0%, which is the concentration previously used
      for the baseline series in most countries. Without causing any more irritant
      reactions, the patch test concentration of 2.0% detects twice as many contact
      allergies and enables the diagnosis of formaldehyde-allergic patients who
      otherwise would have been missed. The studies that underpin the decision were
      performed in Europe and partly in the United States. The Finn Chamber patch test
      system was used. The allergen dose per area was kept uniform with a micropipette.
      This report describes the background for routinely using formaldehyde 2.0%
      instead of 1.0% and for using a micropipette when applying the test solution. 

PMID- 25581666
TI  - Hypersensitivity reactions to titanium: diagnosis and management.
AB  - Titanium is notable for its biocompatibility and is used as biologic implant
      material across surgical specialties, especially in metal-sensitive individuals.
      However, rare cases of titanium hypersensitivity reactions are reported in the
      literature. This article discusses the properties and biological behavior of
      titanium and provides a thorough review of the literature on reported cases,
      diagnostic techniques, and approach to management of titanium hypersensitivity. 

PMID- 25581667
TI  - Treatment of alopecia areata with topical sensitizers.
AB  - For those with severe alopecia areata, with greater than 50% scalp involvement,
      topical immunotherapy with diphenylcyclopropenone or squaric acid dibutylester is
      considered the treatment of choice. This article not only reviews the safety and
      efficacy of topical sensitizers for the treatment of alopecia areata but also
      highlights strides that have been made in the literature concerning their use in
      pediatric populations, molecular mechanisms of efficacy, and improved safety
      through targeted delivery methods. 

PMID- 25581668
TI  - Treatment of warts with contact allergens.
AB  - Contact immunotherapy is an increasingly used, effective means of treating
      cutaneous viral warts. Dinitrochlorobenzene, diphencyprone, and squaric acid
      dibutylester are the most frequently used modalities, showing slight variances in
      adverse effect profiles and efficacy. All of these agents serve as safe treatment
      modalities when administered according to the guidelines recommended herein. We
      review the value of contact immunotherapy in the treatment of cutaneous viral
      warts. 

PMID- 25581669
TI  - Nonallergic reactions to medical tapes.
AB  - BACKGROUND: Adverse dermatologic reactions to tapes are a common problem in the
      medical field and can delay or alter patient care, but their prevalence,
      etiology, and management are poorly defined. OBJECTIVE: The aims of this study
      were to make a distinction between true allergy and nonallergic tape reactions
      (NATRs) to medical tapes and to make recommendations for dermatologists in the
      approach to each. METHODS: We performed a cross-sectional analysis of the
      electronic medical record database at a large hospital system and a review of
      literature. CONCLUSIONS: Although tape allergy is reported by 0.3% of patients,
      true tape allergies are rare. More commonly, patients experience NATRs. True tape
      allergy and NATR are mechanistically distinct and can be distinguished from each
      other based on history. The approach to management of each is distinct.

PMID- 25581670
TI  - Assessment of nickel and cobalt release from jewelry from a non-nickel directive
      country.
AB  - BACKGROUND: A directive restricting nickel release from jewelry and other skin
      contact products has not been initiated in Thailand or in the United States. The
      prevalence of nickel and cobalt allergies is increasing, and the main cause of
      sensitization seems to be jewelry. OBJECTIVES: We aimed to investigate nickel and
      cobalt release from jewelry available in Thai marketplaces and to study the
      factors associated with nickel and cobalt release. METHODS: Used costume jewelry
      items were collected from volunteers. They were tested with the dimethylglyoxime
      and cobalt tests. RESULTS: Five hundred fifty-one items, including belt buckles,
      bracelets, earrings, necklaces, rings, and watches, were tested; 216 (39.2%) gave
      positive dimethylglyoxime tests, and 206 (37.4%) gave positive cobalt tests. The
      factors that determined nickel or cobalt release were shopping location and
      jewelry price. Cobalt-containing jewelry could be identified by its dark color.
      CONCLUSIONS: A large proportion of the jewelry sold in Thai markets release
      nickel or cobalt.

PMID- 25581672
TI  - Novel use of patch testing in the first report of allergic contact dermatitis to
      cyclobenzaprine.

PMID- 25581673
TI  - Topical irritant plus allergen for treatment of warts.

PMID- 25581671
TI  - North American contact dermatitis group patch test results: 2011-2012.
AB  - BACKGROUND: Patch testing is an important diagnostic tool for assessment of
      allergic contact dermatitis (ACD). OBJECTIVE: This study documents the North
      American Contact Dermatitis Group (NACDG) patch-testing results from January 1,
      2011, to December 31, 2012. METHODS: At 12 centers in North America, patients
      were tested in a standardized manner with a series of 70 allergens. Data were
      manually verified and entered into a central database. Descriptive frequencies
      were calculated, and trends analyzed using chi statistics. RESULTS: Four thousand
      two hundred thirty-eight patients were tested; of these, 2705 patients (63.8%)
      had at least 1 positive reaction, and 2029 (48.0%) were ultimately determined to
      have a primary diagnosis of ACD. Four hundred eight patients (9.6%) had
      occupationally related skin disease. There were 7532 positive allergic reactions.
      As compared with previous reporting periods (2009-2010 and 2000-2010), positive
      reaction rates statistically increased for 6 allergens:
      methylchloroisothiazolinone/methylisothiazolinone (5.0%; risk ratios [RRs]: 2.01
      [1.60-2.52], 1.87 [1.61-2.18]), lanolin alcohol (4.6%; RRs 1.83 [1.45-2.30], 2.10
      [1.79-2.47]), cinnamic aldehyde (3.9%; 1.69 [1.32-2.15], 1.53 [1.28-1.82]),
      glutaral (1.5%; 1.67 [1.13-2.48], 1.31 [1.00-1.71]), paraben mix (1.4%; 1.77
      [1.16-2.69], 1.44 [1.09-1.92]), and fragrance mix I (12.1%; RRs 1.42 [1.25-1.61],
      1.24 [1.14-1.36]). Compared with the previous decade, positivity rates for all
      formaldehyde-releasing preservatives significantly decreased (formaldehyde 6.6%;
      RR, 0.82 [0.73, 0.93]; quaternium-15 6.4% RR 0.75 [0.66, 0.85]; diazolidinyl urea
      2.1%; RR, 0.67 [0.54, 0.84]; imidazolidinyl urea 1.6%, 0.60 [0.47, 0.77];
      bronopol 1.6%; RR, 0.60 [0.46, 0.77]; DMDM hydantoin 1.6%; RR, 0.59 [0.54,
      0.84]). Approximately a quarter of patients had at least 1 relevant allergic
      reaction to a non-NACDG allergen. In addition, approximately one-fourth to one
      third of reactions detected by NACDG allergens would have been hypothetically
      missed by T.R.U.E. TEST (SmartPractice Denmark, Hillerod, Denmark). CONCLUSIONS:
      These data document the beginning of the epidemic of sensitivity to
      methylisothiazolinones in North America, which has been well documented in
      Europe. Patch testing with allergens beyond a standard screening tray is
      necessary for complete evaluation of occupational and nonoccupational ACD.

PMID- 25581674
TI  - Allergic contact dermatitis to methylchloroisothiazolinone/methylisothiazolinone
      in cooling tower technicians.

PMID- 25581676
TI  - Next steps in advancing publication.

PMID- 25581675
TI  - Value of R2* obtained from T2*-weighted imaging in predicting the prognosis of
      advanced cervical squamous carcinoma treated with concurrent chemoradiotherapy.
AB  - BACKGROUND: To prospectively investigate the value of R2* in predicting the
      prognosis of advanced cervical squamous carcinoma treated with concurrent
      chemoradiotherapy. METHODS: Sixty-five patients with biopsy-proven cervical
      squamous carcinoma were enrolled in our study. All these subjects underwent multi
      echo T2*-weighted MR imaging on a 3.0 Tesla MR scanner, and tumor R2* was
      calculated. The patients were divided into the responders and the nonresponders
      according to treatment effect. Tumor R2* values of these two groups were
      compared. The relationship between tumor R2* and prognosis after therapy was
      analyzed. RESULTS: The responder group had lower R2* value than the nonresponder
      group (P = 0.02). The area under the receiver operating characteristics curve for
      tumor R2* in discriminating responders from nonresponders was 0.769. A cutoff
      value of 23.87 Hz for tumor R2* resulted in a sensitivity of 78.3% and a
      specificity of 67.6%. The low R2* group (<=28.37 Hz) had longer median
      progression-free survival period and overall survival period (P = 0.01, 0.03).
      Multivariate analysis showed that tumor R2* was a significant prognostic factor
      for progression-free survival and overall survival (adjusted hazards ratio =
      5.34, 4.78; P = 0.02, 0.01). CONCLUSION: R2* value obtained from T2*-weighted
      imaging, as an imaging biomarker, may be an important predictor for the prognosis
      of advanced cervical squamous carcinoma treated with concurrent
      chemoradiotherapy.

PMID- 25581677
TI  - Piperazine analogs of naphthyridine-3-carboxamides and indole-2-carboxamides:
      novel 5-HT3 receptor antagonists with antidepressant-like activity.
AB  - Series of piperazine analogs of naphthyridine-3-carboxamides and indole-2
      carboxamides were designed using a ligand-based approach with consideration of
      the pharmacophoric requirements for 5-HT3 receptor antagonists. The title
      carboxamides were synthesized using appropriate synthetic routes. Initially, the
      5-HT3 receptor antagonistic activity of all the compounds was determined on
      isolated guinea pig ileum tissue against the 5-HT3 agonist, 2-methyl-5
      hydroxytryptamine, which was denoted in the form of pA2 values. The structure
      activity relationship regarding the influence of the aromatic part and basic
      moiety as features in the 5-HT3 pharmacophore was derived. Among all the
      compounds screened, the piperazine derivatives of indole-2-carboxamide 13i and
      naphthyridine-3-carboxamide 8h exhibited prominent 5-HT3 receptor antagonism with
      pA2 values of 7.5 and 7.3, respectively. Subsequent investigation of the
      antidepressant activities of selected compounds in the mouse forced swim test
      (FST) led to the identification of the piperazine analogs of indole-2-carboxamide
      13i and naphthyridine-3-carboxamide 8h as the most promising compounds. Both 13i
      and 8h demonstrated significant reduction in the duration of immobility as
      compared to the control. Importantly, none of the tested compounds affected the
      baseline locomotion of mice at the tested dose levels. 

PMID- 25581678
TI  - Synthesis and cytotoxic activity of pentacyclic triterpenoid sulfamates.
AB  - Methyl triterpenoates derived from oleanolic, ursolic, betulinic, glycyrrhetinic,
      platanic, or maslinic acid were converted into their corresponding sulfamates and
      carbamoylsulfamates. The sulfamates were screened in photometric sulforhodamine
      assays for cytotoxic activity employing several human tumor cell lines. Many of
      the compounds showed EC50 values in one-digit MUM concentration. Of special
      interest seems methyl (3beta) 3-(aminosulfonyloxy)-11-oxo-oleanoate (18) showing
      good cytotoxicity for the human adenocarcinomic alveolar basal epithelial cell
      line A549 while being less toxic for non-malignant NIH 3T3 mouse fibroblasts. 

PMID- 25581682
TI  - Distribution of Minerals in Wheat Grains (Triticum aestivum L.) and in Roller
      Milling Fractions Affected by Pearling.
AB  - The distribution of minerals in (pearled) wheat grains was measured by
      synchrotron X-ray fluorescence, and the impact of pearling (0, 3, 6, 9, and 12%
      by weight) on the mineral composition of flour, shorts, and bran was identified
      by ICP-MS. The xylem mobile elements (Mn, Si, Ca, and Sr) dominated in the
      outermost bran layers, while the phloem mobile elements (K, Mg, P, Fe, Zn, and
      Cu) were more concentrated in the aleurone. Pearling lowered the concentrations
      of xylem mobile elements and increased the concentrations of most phloem mobile
      elements in the pearled grains. Molybdenum, Cd, and especially Se were more
      evenly distributed, and pearling affected their concentrations in milling
      products less. Pearling (3%) increased the concentration of several nutrients (P,
      Zn, Cu) in the flour because the bran fractions reaching the flour are enriched
      in aleurone. The correlations of concentrations of Mg, Fe, Zn, and Cu with that
      of P suggested their association with phytate.

PMID- 25581679
TI  - Marginally designed new profen analogues have the potential to inhibit
      cyclooxygenase enzymes.
AB  - The current structure-activity relationship of profens (i.e., 2-arylpropionic
      acid derivatives, a class of non-steroidal anti-inflammatory drugs) discusses the
      importance of alpha-monomethyl substitution on these compounds, since the
      activities obtained through their corresponding arylacetic acid derivatives
      (i.e., alpha-demethylated derivatives) or alpha,alpha-dimethyl-substituted
      compounds are less than what is observed for the parent profens. Unfortunately,
      this implies a generalization in structure-activity relationships of profens in
      such a way that a mono-(non-methyl)alkyl group or dialkyl substituent replaced at
      the alpha-position of a profen analogue results in abolished activity. Therefore,
      within this study, we aimed to question this generalization employing ibuprofen,
      flurbiprofen, and naproxen as model compounds. A series of alpha-(non
      methyl)alkyl-substituted ibuprofen and flurbiprofen analogues as well as
      alpha,alpha-dialkyl-substituted ibuprofen, flurbiprofen, and naproxen derivatives
      were synthesized and screened for their potential to inhibit cyclooxygenase
      enzymes. In addition, since profens have negligible potential to inhibit
      lipoxygenase enzymes, the effect of such derivatization was also questioned in
      lipoxygenase inhibition assays. The findings only partially agreed with the
      current structure-activity approach of profens and the activity results of some
      compounds were found as beyond ordinary. 

PMID- 25581683
TI  - Natural products as zinc-dependent histone deacetylase inhibitors.
AB  - Zinc-dependent histone deacetylases (HDACs), a family of hydrolases that remove
      acetyl groups from lysine residues, play an important role in the regulation of
      multiple processes, from gene expression to protein activity. The dysregulation
      of HDACs is associated with many diseases including cancer, neurological
      disorders, cellular metabolism disorders, and inflammation. Molecules that act as
      HDAC inhibitors (HDACi) exhibit a variety of related bioactivities. In
      particular, HDACi have been applied clinically for the treatment of cancers.
      Inhibition through competitive binding of the catalytic domain of these enzymes
      has been achieved by a diverse array of small-molecule chemotypes, including a
      number of natural products. This review provides a systematic introduction of
      natural HDACi, with an emphasis on their enzyme inhibitory potency, selectivity,
      and biological activities, highlighting their various binding modes with HDACs. 

PMID- 25581685
TI  - Low temperature critical growth of high quality nitrogen doped graphene on
      dielectrics by plasma-enhanced chemical vapor deposition.
AB  - Nitrogen doping is one of the most promising routes to modulate the electronic
      characteristic of graphene. Plasma-enhanced chemical vapor deposition (PECVD)
      enables low-temperature graphene growth. However, PECVD growth of nitrogen doped
      graphene (NG) usually requires metal-catalysts, and to the best of our knowledge,
      only amorphous carbon-nitrogen films have been produced on dielectric surfaces by
      metal-free PECVD. Here, a critical factor for metal-free PECVD growth of NG is
      reported, which allows high quality NG crystals to be grown directly on
      dielectrics like SiO2/Si, Al2O3, h-BN, mica at 435  degrees C without a catalyst.
      Thus, the processes needed for loading the samples on dielectrics and n-type
      doping are realized in a simple PECVD, which would be of significance for future
      graphene electronics due to its compatibility with the current microelectronic
      processes.

PMID- 25581684
TI  - Epigenetic changes during mechanically induced osteogenic lineage commitment.
AB  - Osteogenic lineage commitment is often evaluated by analyzing gene expression.
      However, many genes are transiently expressed during differentiation. The
      availability of genes for expression is influenced by epigenetic state, which
      affects the heterochromatin structure. DNA methylation, a form of epigenetic
      regulation, is stable and heritable. Therefore, analyzing methylation status may
      be less temporally dependent and more informative for evaluating lineage
      commitment. Here we analyzed the effect of mechanical stimulation on osteogenic
      differentiation by applying fluid shear stress for 24 hr to osteocytes and then
      applying the osteocyte-conditioned medium (CM) to progenitor cells. We analyzed
      gene expression and changes in DNA methylation after 24 hr of exposure to the CM
      using quantitative real-time polymerase chain reaction and bisulfite sequencing.
      With fluid shear stress stimulation, methylation decreased for both adipogenic
      and osteogenic markers, which typically increases availability of genes for
      expression. After only 24 hr of exposure to CM, we also observed increases in
      expression of later osteogenic markers that are typically observed to increase
      after seven days or more with biochemical induction. However, we observed a
      decrease or no change in early osteogenic markers and decreases in adipogenic
      gene expression. Treatment of a demethylating agent produced an increase in all
      genes. The results indicate that fluid shear stress stimulation rapidly promotes
      the availability of genes for expression, but also specifically increases gene
      expression of later osteogenic markers. 

PMID- 25581686
TI  - Effects of particle size and porosity on in vivo remodeling of settable allograft
      bone/polymer composites.
AB  - Established clinical approaches to treat bone voids include the implantation of
      autograft or allograft bone, ceramics, and other bone void fillers (BVFs).
      Composites prepared from lysine-derived polyurethanes and allograft bone can be
      injected as a reactive liquid and set to yield BVFs with mechanical strength
      comparable to trabecular bone. In this study, we investigated the effects of
      porosity, allograft particle size, and matrix mineralization on remodeling of
      injectable and settable allograft/polymer composites in a rabbit femoral condyle
      plug defect model. Both low viscosity and high viscosity grafts incorporating
      small (<105 MUm) particles only partially healed at 12 weeks, and the addition of
      10% demineralized bone matrix did not enhance healing. In contrast, composite
      grafts with large (105-500 MUm) allograft particles healed at 12 weeks
      postimplantation, as evidenced by radial MUCT and histomorphometric analysis.
      This study highlights particle size and surface connectivity as influential
      parameters regulating the remodeling of composite bone scaffolds.

PMID- 25581687
TI  - Recombinant human soluble thrombomodulin in severe sepsis: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Although recombinant human soluble thrombomodulin (rhTM) is a widely
      used novel anticoagulant agent for disseminated intravascular coagulation (DIC)
      in Japan, its clinical efficacy in sepsis-induced DIC has not been demonstrated
      convincingly. OBJECTIVE: To assess the benefits and harms of rhTM in sepsis
      induced DIC patients. METHODS: We conducted a systematic review and meta-analysis
      of rhTM therapy for sepsis-induced DIC for both randomized controlled trials
      (RCTs) and observational studies (retrospective case-control studies and/or
      prospective cohort studies) separately. All-cause mortality (28-30 days) as
      efficacy and serious bleeding complications as adverse effect were measured as
      primary outcomes. We assessed body of evidence quality at the outcome level by
      using the Grading of Evidence, Assessment, Development and Evaluation (GRADE)
      approach. RESULTS: We analyzed 12 studies (838 patients/3 RCTs; 571 patients/9
      observational studies). Pooled relative risk was 0.81 (95% CI, 0.62-1.06) in the
      RCTs, indicating non-significant reduction in mortality, and 0.59 (95% CI, 0.45
      0.77) in the observational studies. Meta-regression analysis revealed a
      significant negative slope between effect size of rhTM therapy and baseline
      mortality rate in individual studies (P = 0.012), suggesting that probability of
      a beneficial effect with rhTM therapy increases with increasing baseline risk.
      Risk of serious bleeding complications was not significantly different between
      rhTM and control groups. We judged the quality of evidence as moderate for
      mortality and serious bleeding. CONCLUSIONS: The rhTM was associated with a trend
      in reduction of mortality at 28-30 days in sepsis-induced DIC patients. Further
      large rigorous trials are needed to confirm or refute these findings before
      implications for practice are clear.

PMID- 25581688
TI  - Wound samples: moving towards a standardised method of collection and analysis.
AB  - Chronic wounds, including diabetic foot ulcers, pressure ulcers and venous leg
      ulcers, impact the lives of millions of people worldwide. These types of wounds
      represent a significant physical, social and financial burden to both patients
      and health care systems. Wound care has made great progress in recent years as a
      result of the critical research performed in academic, clinical and industrial
      settings. However, there has been relatively little translation of basic research
      discoveries into novel and effective treatments. One underlying reason for this
      paucity may be inconsistency in the methods of wound analysis and sample
      collection, resulting in the inability of researchers to accurately characterise
      the healing process and compare results from different studies. This review
      examines the various types of analytical methods being used in wound research
      today with emphasis on sampling techniques, processing and storage, and the
      findings call forth the wound care research community to standardise its approach
      to wound analysis in order to yield more robust and comparable data sets. 

PMID- 25581689
TI  - A comparison of cardiopulmonary exercise test and 6 minute walking test in
      determination of exercise capacity in chronic obstructive pulmonary disease.
AB  - INTRODUCTION: This study aimed to determine the relationship of 6 minute walking
      test (6MWT) and cardiopulmonary exercise test (CPET) with each other and with the
      measures of lung functions in patients with chronic obstructive pulmonary disease
      (COPD). MATERIALS AND METHODS: Pulmonary function tests, 6MWT, and CPET were
      performed in 36 (35 males, 1 female) patients with moderate and severe COPD.
      RESULTS: Maximum oxygen uptake was significantly correlated with 6 minute walking
      distance. Both exercise tests were correlated with pulmonary function tests.
      However, maximum exercise capacity was more closely correlated with measures of
      lung function than 6MWT. Both tests were significantly correlated with static
      lung volumes. Inspiratory capacity (IC) was significantly correlated with 6MWT
      and CPET parameters. CPET was significantly correlated with diffusion capacity
      and maximal inspiratory pressure. Airway conductance and resistance tests showed
      no correlation with the exercise tests. CONCLUSION: 6MWT is a simple and valuable
      test to determine the exercise capacity of COPD patients. Both 6MWT and CPET are
      correlated with ventilatory impairment determined by the lung function tests,
      particularly FEV1, maximum voluntary ventilation (MVV), and IC. However, CPET is
      an exercise test that more accurately evaluates and provides more detailed
      information about hyperinflation and respiratory musce strength than 6MWT does.

PMID- 25581690
TI  - [Elevated pleural copeptin levels can distinguish to exudate from transudates].
AB  - INTRODUCTION: Copeptin is released simultaneously along with arginine
      vasopressine as a result of different stimuli from the neurohypophysis.
      Physiological function of copeptin is still unclear. Increased blood copeptin
      levels is associated with poor prognosis in many diseases. Pleural effusion is a
      common clinical condition. The most common causes of pleural effusions are heart
      failure, parapneumonic effusion, pulmonary embolism and malignacy.Tuberculosis is
      one of the other major causes of pleural effusion in developing countries. In
      this study, we aimed to assess whether pleural copeptin level may be a new
      discriminative biomarker for exudates and transudates pleural effusions.
      MATERIALS AND METHODS: Research was done at Recep Tayyip Erdogan University
      School of Medicine in the Department of Chest Diseases. The concentrations of
      pleural copeptin and typical pleural and serum marker levels were measured in 76
      subjects with pleural effusions including 22 transudates caused by congestive
      heart failure (CHF), and 54 exudates including 18 parapneumonic (PPE), 18
      tuberculous pleural effusions (TBPEs), 18 malignant effusions (MPEs). RESULTS:
      Median pleural fluid copeptin levels were higher in exudates than in transudates
      (1936 ng/mL and 1313 pg/mL, p value < 0.001). There was no statistical
      significancy for pleural fluid copeptin levels with in-group exudates (n= 54).
      Pleural copeptin levels of exudates, with a cut off value of 1469 ng/mL, yielded
      a 79.6% sensitivity, 81.8% specificity, with an are a under the curve of 0.851.
      CONCLUSION: Pleural copeptin level is a new biomarker to separate exudates from
      transudates. Pleural effusion discriminative effect of copeptin is lower than
      plasma protein level and plasma lactat dehydrogenase (LDH). Pleural copeptin
      measurement is not recommended for routine clinical use. Pleural copeptin level
      is not contribute to different iate exudative pleural fluids from each other like
      PPE, TBPE and MPE.

PMID- 25581691
TI  - The place of YKL-40 in non-small cell lung cancer.
AB  - INTRODUCTION: Despite varies treatment options, the survival rate of non-small
      cell lung cancer (NSCLC) is less than 1%. If biological behaviour of any cancer
      could be known, the information would potentially tailor the clinical work-up,
      assessment and treatment. The prognostic value of serum YKL-40 level has been
      investigated in different types of cancer and showed poor prognostic indication
      with more aggressive clinical course. We studied the role of serum YKL-40 levels
      in patients with NSCLC to determine the stage. MATERIALS AND METHODS: Serum YKL
      40 levels in venous blood samples of 55 patients was studied. 49 (89.1%) male and
      6 (10.9%) female newly diagnosed NSCLC patients whom received neither cancer
      specific or symptom relieving treatment are enrolled. TNM staging was determined
      based on the findings of computerized tomography (CT), positron emission
      tomography (PET), cranial magnetic resonance imaging (MRI), bronchoscopy and
      mediastinoscopy. The patients with NSCLC were divided into two groups; Group A:
      stage Ia, Ib, IIa, IIb, Group B: stage IIIa, IIIb and IV. RESULTS: There was a
      statistical difference in YKL-40 serum levels between groups (Group A, Group B)
      when compared (p< 0.05). A medium and statistical correlation was found (r= 0.48;
      p< 0.01) between YKL-40 levels and age. CONCLUSION: YKL-40 levels in advanced
      stage NSCLC (stage III, IV) was found to be significantly high compared to early
      stage. It should be kept in mind that when YKL levels are high, higher stages of
      the disease should be suspected and future tests should be performed.

PMID- 25581692
TI  - Place of vibration response imaging in preoperative lung cancer patients.
AB  - INTRODUCTION: In this study, we aimed to investigate the role of the vibration
      response imaging (VRI) as the second-line test in preoperative evaluation of the
      patients with non-small cell lung cancer (NSCLC) and in prediction of the
      predicted postoperative forced expiratory volume in one second (ppo FEV1).
      MATERIALS AND METHODS: A total of 31 patients scheduled for surgery underwent
      pulmonary function tests (PFTs), VRIxp and quantitative lung perfusion
      scintigraphy (LPS) in order to predict postoperative lung functions. PFTs and VRI
      were repeated between 4th and 6th postoperative weeks and FEV1 and FEV1% values
      were compared with preoperative VRI and ppo-FEV1 calculated with perfusion
      scintigraphy. Statistical analysis of 31 patients under postoperative follow-up
      was performed in two parts. In the first part, two preoperative prediction
      methods (ppo based on perfusion and ppo calculated with VRI), and in the second
      part, estimated values and postoperative actual values (considering postoperative
      spirometric values as standard) were compared. RESULTS: An agreement rate of 52%
      was found between the ppo values calculated with VRI and with perfusion. This
      rate was low, although respective predictive values for ppo VRI and ppo perfusion
      were 84% and 47%, suggesting that ppo VRI was more significant than LPS for
      prediction of the 1st month postoperative value in the patients included in this
      study. CONCLUSIONS: VRIxp has a high-accuracy rate in prediction postoperative
      FEV1. It is seemed as an alternative to quantitative perfusion scintigraphy for
      preoperative evaluation, because it can be easily applied at the bedside as a
      radiation free and non-invasive method.

PMID- 25581693
TI  - [Latent tuberculosis treatment results in patients that taken TNF-alpha blockers
      at Ankara Numune Training and Research Hospital Chest Diseases Clinic for last 8
      years (2006-2013)].
AB  - INTRODUCTION: Tuberculosis occurrence was evaluated in patients that applied
      tuberculosis chemoprophylaxis and currently receiving tumor necrosis factor-alpha
      (TNF-alpha) blocker. MATERIALS AND METHODS: Incidence of tuberculosis were
      retrospectively evaluated in patients that currently receiving TNF-alpha-blocking
      therapy and received tuberculosis chemoprophylaxis at Ankara Numune Education and
      Research Hospital, Lung Disease Department, between 2006-2013 years. 134 patients
      that were diagnosed with rheumatologic and dermatologic diseases, were evaluated.
      Patients were in the age range 18-80 years. Age, gender, smoking status, BCG
      vaccination, chest radiography, diagnose of disease, presence of concomitant
      disease, tuberculosis story, PPD value, chemoprophylaxis acquisition, which anti
      tuberculosis agents received, duration of chemoprophylaxis, duration of TNF-alpha
      blocker, other immunosuppressive using were measured. RESULTS: Rheumatologic
      diseases were often. Prophylaxis has given at 73.9% of patients. Patients with
      received anti-TNF-alpha therapy (n= 134) have not developed pulmonary or extra
      pulmonary tuberculosis disease. CONCLUSION: Patients with received anti-TNF-alpha
      therapy, are scanned with TST or Quantiferon. If latent tuberculosis infection
      are diagnosed, tuberculosis prophylaxis should be started pre-anti-TNF-alpha
      therapy at least one month and INH chemoprophylaxis should be completed on 9
      months or RIF should be completed on 4 months. Serum liver enzymes and bilirubin
      measurements monthly; follow-up physical examination and chest radiography should
      be performed for 3 months.

PMID- 25581694
TI  - [Bronchial thermoplasty; a new treatment modality in asthma].
AB  - Bronchial thermoplasty is a non-drug treatment modality for moderate-to-severe
      asthma that involves the delivery of radio frequency energy to the airway wall in
      a precisely controlled manner to reduce excessive airway smooth muscle. Bronchial
      thermoplasty is performed under conscious sedation and completed in three
      bronchoscopy sessions, each lasting less than one hour, and each spaced apart by
      about three weeks. Bronchial thermoplasty has been demonstrated to reduce severe
      exacerbations, emergency rooms visits for respiratory symptoms, and time lost
      from work, school and other daily activities and improve asthma control and
      quality of life in patients with moderate-to-severe asthma. Adequate patient
      management is important for patient comfort and safety. In this review, we aim to
      discuss clinical studies , the evidence for the efficacy of bronchial
      thermoplasty, the importance of careful patient selection, patient preparation,
      patient management, procedure.

PMID- 25581695
TI  - [Venous thromboembolism and cancer].
AB  - Venous thromboembolism (VTE) is one of the complications which have significant
      influence on mortality in patient with cancer. Early mortality rate is high in
      cancer patients who have VTE. This complication is related with cell type and
      stage of the cancer, surgery applied during cancer treatment, applying catheter
      and the chemotherapeutic agents. VTE prophylaxis and/or treatment in treatment
      and follow-up of cancer patients will provide a reduction in mortality and
      morbidity rates. VTE prophylaxis and treatment poses differences according to
      both treatment approaches which will be applied and the type of cancer. It has
      been aimed to describe pathogenesis, risk factors and treatment approaches taking
      into account international consensus reports in this review. 

PMID- 25581696
TI  - A rare complication of acupuncture: pneumothorax.

PMID- 25581697
TI  - Respiratory failure in Robinow syndrome was treated with non-invasive mechanical
      ventilation for the first time.

PMID- 25581698
TI  - Recurrent bilateral pneumothorax complicating miliary tuberculosis with bone
      marrow involvement.

PMID- 25581699
TI  - QuantiFERON-TB gold in-tube test vs. tuberculin skin test.

PMID- 25581700
TI  - Electrocardiogram in emphysema: a rapid bedside screening diagnostic tool.

PMID- 25581702
TI  - Relations between negative affect and health behaviors by race/ethnicity:
      Differential effects for symptoms of depression and anxiety.
AB  - OBJECTIVE: Health behaviors, including smoking and fruit and vegetable
      consumption, are both associated with psychological distress and vary by
      race/ethnicity. The relation of global psychological distress to behavior also
      varies by race/ethnicity, but the specific negative affective states responsible
      for this effect are not known. This study examined how the relation of feelings
      of depression and anxiety to health behaviors differs by race/ethnicity. METHOD:
      Secondary data analysis of the HINTS nationally representative population survey
      was conducted. Survey participants reported their current symptoms of depression
      and anxiety, as well as smoking status and fruit and vegetable consumption.
      Survey weighted linear and logistic regression analyses were used to assess
      whether race/ethnicity moderated the relation of symptoms of depression and
      anxiety to smoking and fruit and vegetable consumption. RESULTS: For symptoms of
      depression, but not anxiety, there was a significant interaction between
      race/ethnicity and psychological distress in predicting both smoking status and
      fruit and vegetable consumption. Greater depressive symptoms were related to a
      greater likelihood of smoking and lower fruit and vegetable consumption for
      White, but not Black respondents. For Hispanic respondents, depressive symptoms
      were associated with a greater likelihood of currently smoking, but were not
      associated with fruit and vegetable consumption. CONCLUSION: The association
      between depressive symptoms and both smoking and fruit and vegetable consumption
      differs as a function of race/ethnicity. These findings have implications for
      understanding the extent to which negative affective states influence health
      behaviors across different racial/ethnic groups, and for developing interventions
      that effectively target smoking and fruit and vegetable consumption among
      different racial/ethnic subgroups.

PMID- 25581703
TI  - Increasing condom use by changing people's feelings about them: An experimental
      study.
AB  - OBJECTIVE: Given the well-documented efficacy of condoms as a means of preventing
      pregnancy and sexually transmitted infection transmission, the low rates of
      condom use among young adults necessitates a deeper understanding of the factors
      that influence condom use decision making. The central purpose of the current
      study was to examine how experimentally manipulated affective associations with
      condoms influence subsequent behavior in a condom selection task, thereby
      providing support for a causal relation of affective associations to behavior in
      this health domain. METHOD: Following a baseline assessment of cognitively based
      beliefs and affective associations, participants' (N = 171) affective
      associations with condoms were experimentally manipulated with an evaluative
      conditioning (EC) procedure. Images of condoms were paired repeatedly with
      positive or neutral affective stimuli. The key outcome measure was a behavioral
      choice task in which participants selected condoms upon completion of the
      experiment. RESULTS: Participants in the positive condition reported more
      positive affective associations post-EC compared with those in the neutral
      condition, beta = 0.33, p = .025, 95% CI (0.041, 0.63). For participants who
      regularly used condoms at baseline, those in the positive condition also selected
      significantly more condoms, RR = 1.39, p = .015, 95% CI (1.07, 1.83). This
      condition effect on behavior was partially mediated by the change in affective
      associations. There was no effect of condition on condom selection among
      participants who rarely used condoms at baseline. CONCLUSION: The current study
      extends our theoretical understanding of the affect-behavior relation in the
      realm of condom use, and provides preliminary support for interventions that
      target affective associations with condoms.

PMID- 25581701
TI  - Associations between coping and diurnal cortisol among children affected by
      parental HIV/AIDS.
AB  - OBJECTIVE: Prior research has shown that early life adversity is associated with
      physical health problems, but little is known about the health-related effects of
      coping in the context of having a parent with HIV/AIDS. The goal of this study
      was to investigate the associations between positive and negative coping
      strategies and diurnal cortisol among children affected by parental HIV/AIDS.
      METHOD: Participants were 645 children aged 8-15 affected by parental HIV/AIDS,
      who provided 4 saliva samples per day over 3 days (2 weekdays and 1 weekend day)
      to assess diurnal cortisol. Positive and negative coping strategies were measured
      via self-report prior to saliva collection. Possible confounds of the
      associations between coping and diurnal cortisol also were assessed, including
      age, gender, socioeconomic status, parenting quality, parental death, other
      stressful life events, sleep quality, and perceived health status. RESULTS:
      Greater positive coping (e.g., problem solving, cognitive reframing) was
      associated with children's higher morning cortisol (p = .037), whereas greater
      negative coping (e.g., fighting, breaking things) was independently associated
      with lower morning cortisol (p = .038) and a flatter diurnal cortisol slope (p =
      .003). These associations remained significant after controlling for potential
      confounds. Neither positive coping nor negative coping interacted with stressful
      life circumstances to predict cortisol (all ps > .27). CONCLUSION: These findings
      indicate the extent to which a child's coping strategy is associated with
      indicators of stress biology in the context of having a parent with HIV/AIDS.

PMID- 25581704
TI  - Depression mediates and moderates effects of methamphetamine use on sexual risk
      taking among treatment-seeking gay and bisexual men.
AB  - OBJECTIVE: Mounting evidence suggests a syndemic relation between methamphetamine
      use and depression to increase sexual risk taking (i.e., HIV transmission risk
      behavior) among men who have sex with men. This prospective analysis of
      longitudinal data collected from an outpatient methamphetamine abuse treatment
      program for gay and bisexual men assessed whether symptoms of depression mediated
      and/or moderated the associations between methamphetamine use and unprotected
      insertive/receptive anal intercourse. METHOD: From November 2005 through October
      2007, 167 treatment-seeking gay and bisexual men (63% HIV-positive) enrolled in
      and attended a 16-week methamphetamine abuse outpatient treatment program.
      Participants' depressive symptoms, biomarker-confirmed methamphetamine use, and
      self-reported sexual risk taking were assessed at baseline and follow-up
      evaluations. Path analysis tested the mediating and moderating effects of
      depression on the associations between methamphetamine use and unprotected
      insertive/receptive anal intercourse. RESULTS: Methamphetamine use during the
      treatment period had a significant indirect (Coef. = -.15; 95% CI [-.23, -.06]),
      but no direct (Coef. = .11; ns) or total effect (Coef. = -.04; ns) on
      participants' sexual risk taking after accounting for the significant mediating
      (Coef. = .56; 95% CI [.33, .78]) and moderating (Coef. = -.03; 95% CI [-.04, 
      .02]) effects of depression. CONCLUSIONS: Depression fully mediated and weakly
      moderated associations between methamphetamine use and sexual risk taking in this
      sample. Interventions and treatment programs to reduce sexual risk taking among
      gay and bisexual men should simultaneously address methamphetamine use and
      depression to optimize health outcomes.

PMID- 25581705
TI  - Enhanced resistance to soybean cyst nematode Heterodera glycines in transgenic
      soybean by silencing putative CLE receptors.
AB  - CLE peptides are small extracellular proteins important in regulating plant
      meristematic activity through the CLE-receptor kinase-WOX signalling module. Stem
      cell pools in the SAM (shoot apical meristem), RAM (root apical meristem) and
      vascular cambium are controlled by CLE signalling pathways. Interestingly, plant
      parasitic cyst nematodes secrete CLE-like effector proteins, which act as ligand
      mimics of plant CLE peptides and are required for successful parasitism.
      Recently, we demonstrated that Arabidopsis CLE receptors CLAVATA1 (CLV1), the
      CLAVATA2 (CLV2)/CORYNE (CRN) heterodimer receptor complex and RECEPTOR-LIKE
      PROTEIN KINASE 2 (RPK2), which transmit the CLV3 signal in the SAM, are required
      for perception of beet cyst nematode Heterodera schachtii CLEs. Reduction in
      nematode infection was observed in clv1, clv2, crn, rpk2 and combined double and
      triple mutants. In an effort to develop nematode resistance in an agriculturally
      important crop, orthologues of Arabidopsis receptors including CLV1, CLV2, CRN
      and RPK2 were identified from soybean, a host for the soybean cyst nematode
      Heterodera glycines. For each of the receptors, there are at least two paralogues
      in the soybean genome. Localization studies showed that most receptors are
      expressed in the root, but vary in their level of expression and spatial
      expression patterns. Expression in nematode-induced feeding cells was also
      confirmed. In vitro direct binding of the soybean receptors with the HgCLE
      peptide was analysed. Knock-down of the receptors in soybean hairy roots showed
      enhanced resistance to SCN. Our findings suggest that targeted disruption of
      nematode CLE signalling may be a potential means to engineer nematode resistance
      in crop plants. 

PMID- 25581706
TI  - Reversible lacrimal gland-protective regulatory T-cell dysfunction underlies male
      specific autoimmune dacryoadenitis in the non-obese diabetic mouse model of
      Sjogren syndrome.
AB  - CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells are required to maintain
      immunological tolerance; however, defects in specific organ-protective Treg cell
      functions have not been demonstrated in organ-specific autoimmunity. Non-obese
      diabetic (NOD) mice spontaneously develop lacrimal and salivary gland
      autoimmunity and are a well-characterized model of Sjogren syndrome. Lacrimal
      gland disease in NOD mice is male-specific, but the role of Treg cells in this
      sex-specificity is not known. This study aimed to determine if male-specific
      autoimmune dacryoadenitis in the NOD mouse model of Sjogren syndrome is the
      result of lacrimal gland-protective Treg cell dysfunction. An adoptive transfer
      model of Sjogren syndrome was developed by transferring cells from the lacrimal
      gland-draining cervical lymph nodes of NOD mice to lymphocyte-deficient NOD-SCID
      mice. Transfer of bulk cervical lymph node cells modelled the male-specific
      dacryoadenitis that spontaneously develops in NOD mice. Female to female
      transfers resulted in dacryoadenitis if the CD4(+) CD25(+) Treg-enriched
      population was depleted before transfer; however, male to male transfers resulted
      in comparable dacryoadenitis regardless of the presence or absence of Treg cells
      within the donor cell population. Hormone manipulation studies suggested that
      this Treg cell dysfunction was mediated at least in part by androgens.
      Surprisingly, male Treg cells were capable of preventing the transfer of
      dacryoadenitis to female recipients. These data suggest that male-specific
      factors promote reversible dysfunction of lacrimal gland-protective Treg cells
      and, to our knowledge, form the first evidence for reversible organ-protective
      Treg cell dysfunction in organ-specific autoimmunity.

PMID- 25581707
TI  - Structural characterization of O- and C-glycosylating variants of the landomycin
      glycosyltransferase LanGT2.
AB  - The structures of the O-glycosyltransferase LanGT2 and the engineered, C-C bond
      forming variant LanGT2S8Ac show how the replacement of a single loop can change
      the functionality of the enzyme. Crystal structures of the enzymes in complex
      with a nonhydrolyzable nucleotide-sugar analogue revealed that there is a
      conformational transition to create the binding sites for the aglycon substrate.
      This induced-fit transition was explored by molecular docking experiments with
      various aglycon substrates.

PMID- 25581709
TI  - Single-crystal field-effect transistors of new Cl2-NDI polymorph processed by
      sublimation in air.
AB  - Physical properties of active materials built up from small molecules are
      dictated by their molecular packing in the solid state. Here we demonstrate for
      the first time the growth of n-channel single-crystal field-effect transistors
      and organic thin-film transistors by sublimation of 2,6-dichloro-naphthalene
      diimide in air. Under these conditions, a new polymorph with two-dimensional
      brick-wall packing mode (beta-phase) is obtained that is distinguished from the
      previously reported herringbone packing motif obtained from solution (alpha
      phase). We are able to fabricate single-crystal field-effect transistors with
      electron mobilities in air of up to 8.6 cm(2) V(-1) s(-1) (alpha-phase) and up to
      3.5 cm(2) V(-1) s(-1) (beta-phase) on n-octadecyltriethoxysilane-modified
      substrates. On silicon dioxide, thin-film devices based on beta-phase can be
      manufactured in air giving rise to electron mobilities of 0.37 cm(2) V(-1) s(-1).
      The simple crystal and thin-film growth procedures by sublimation under ambient
      conditions avoid elaborate substrate modifications and costly vacuum equipment
      based fabrication steps.

PMID- 25581708
TI  - Time Trends in Helicobacter pylori Infection and Atrophic Gastritis Over 40 Years
      in Japan.
AB  - BACKGROUND: Helicobacter pylori infection produces progressive mucosal damage
      that may eventually result in gastric cancer. We studied the changes that
      occurred in the presence and severity of atrophic gastritis and the prevalence of
      H. pylori infection that occurred coincident with improvements in economic and
      hygienic conditions in Japan since World War II. MATERIALS AND METHODS: The
      prevalence of H. pylori infection and histologic grades of gastric damage were
      retrospectively evaluated using gastric biopsy specimens obtained over a 40-year
      period. Gastric atrophy and intestinal metaplasia were scored using the updated
      Sydney classification system. RESULTS: The prevalence of H. pylori and severity
      of atrophy were examined in 1381 patients including 289 patients examined in the
      1970s (158 men; mean age, 44.9 years), 787 in the 1990s (430 men; 44.2 years),
      and 305 in the 2010s (163 men; 53.2 years). Overall, the prevalence of H. pylori
      infection decreased significantly from 74.7% (1970s) to 53% (1990s) and 35.1%
      (2010s) (p < .01). The prevalence of atrophy in the antrum and corpus was
      significantly lower in the 2010s (33, 19%, respectively) compared to those
      evaluated in either the 1970s (98, 82%) (p < .001) or 1990s (80, 67%) (p < .001).
      The severity of atrophy and intestinal metaplasia also declined remarkably among
      those with H. pylori infection. CONCLUSIONS: There has been a progressive and
      rapid decline in the prevalence of H. pylori infection as well a fall in the rate
      of progression of gastric atrophy among H. pylori-infected Japanese coincident
      with the westernization and improvements in economic and hygienic conditions in
      Japan since World War II.

PMID- 25581710
TI  - Early-life stress induces anxiety-like behaviors and activity imbalances in the
      medial prefrontal cortex and amygdala in adult rats.
AB  - Early-life stress increases the prevalence of psychiatric diseases associated
      with emotional dysregulation. Emotional regulation requires the inhibitory
      influence of the medial prefrontal cortex (mPFC) on amygdalar activity, and
      dysfunction of this system is believed to induce anxiety. Because mPFC and
      amygdala have dense reciprocal connections and projections between them continue
      to develop until adolescence, early-life stress may impair the function of this
      circuit and cause emotional dysregulation. We examined the effects of stress
      during circuit development on anxiety-like behaviors, neural activities in the
      mPFC and amygdala, and impulse transmission in the mPFC-amygdala circuit in adult
      rats. Early-life stress, unpredictable stress twice a day for 12 days following
      early weaning, increased anxiety-like behaviors in the open-field and elevated
      plus-maze tests. In the open-field test, stress altered Fos expression in the
      mPFC and amygdala. Compared to non-stressed rats, which were exposed to neither
      unpredictable stress nor early weaning, stressed rats exhibited decreased Fos
      expression in the right superficial layers of the infralimbic cortex and
      increased Fos expression in the right basolateral amygdala and both sides of the
      central amygdala. Electrophysiological analysis revealed that excitatory
      latencies of mPFC neurons to amygdalar stimulation in stressed rats were
      significantly longer than control rats in the right, but not left, hemisphere.
      Stress had no effect on excitatory latencies of amygdalar neurons to mPFC
      stimulation in the mPFC-amygdala circuits in the both hemisphere. These data
      suggest that early-life stress impairs the mPFC-amygdala circuit development,
      resulting in imbalanced mPFC and amygdala activities and anxiety-like behaviors.

PMID- 25581711
TI  - Rectus sheath block for laparoscopic appendicectomy: a randomized clinical trial.
AB  - BACKGROUND: The rectus sheath block is effective in elective paediatric
      operations, but has not been previously studied in acute laparoscopic surgery. We
      investigated its effect on pain after laparoscopic appendicectomy for acute
      appendicitis. METHODS: Children aged 8-14 years admitted to a paediatric teaching
      hospital participated in a randomized clinical trial comparing a rectus sheath
      block using bupivacaine plus adrenaline with saline control. The primary outcomes
      were pain scores and opiate use, and secondary outcomes were time in the post
      anaesthetic care unit, duration of hospitalization and recovery. RESULTS:
      Children in the nerve block group reported significantly reduced global pain
      scores compared with controls in the first 3 h after surgery, estimated mean 2.22
      versus 3.94, effect size -1.80 (P = .008). Pain scores after 3 h did not differ
      between the groups. The groups did not differ in opiate requirements, length of
      hospital stay or recovery after discharge. CONCLUSIONS: In children undergoing
      acute laparoscopic appendicectomy, a rectus sheath block reduced early post
      operative pain, and could contribute to a multimodal recovery programme.

PMID- 25581713
TI  - Non-selective beta-blockers may reduce risk of hepatocellular carcinoma: a meta
      analysis of randomized trials.
AB  - BACKGROUND & AIMS: Non-selective beta-blockers (NSBB) are used in patients with
      cirrhosis and oesophageal varices. Experimental data suggest that NSBB inhibit
      angiogenesis and reduce bacterial translocation, which may prevent hepatocellular
      carcinoma (HCC). We therefore assessed the effect of NSBB on HCC by performing a
      systematic review with meta-analyses of randomized trials. METHODS: Electronic
      and manual searches were combined. Authors were contacted for unpublished data.
      Included trials assessed NSBB for patients with cirrhosis; the control group
      could receive any other intervention than NSBB. Fixed and random effects meta
      analyses were performed with I(2) as a measure of heterogeneity. Subgroup,
      sensitivity, regression and sequential analyses were performed to evaluate
      heterogeneity, bias and the robustness of the results after adjusting for
      multiple testing. RESULTS: Twenty-three randomized trials on 2618 patients with
      cirrhosis were included, of which 12 reported HCC incidence and 23 reported HCC
      mortality. The mean duration of follow-up was 26 months (range 8-82). In total,
      47 of 694 patients randomized to NSBB developed HCC vs 65 of 697 controls (risk
      difference -0.026; 95% CI-0.052 to -0.001; number needed to treat 38 patients).
      There was no heterogeneity (I(2) = 7%) or evidence of small study effects (Eggers
      P = 0.402). The result was not confirmed in sequential analysis, which suggested
      that 3719 patients were needed to achieve the required information size. NSBB did
      not reduce HCC-related mortality (RD -0.011; 95% CI -0.040 to 0.017).
      CONCLUSIONS: Non-selective beta-blockers may prevent HCC in patients with
      cirrhosis.

PMID- 25581714
TI  - Drinking cholera: salinity levels and palatability of drinking water in coastal
      Bangladesh.
AB  - OBJECTIVES: To measure the salinity levels of common water sources in coastal
      Bangladesh and explore perceptions of water palatability among the local
      population to investigate the plausibility of linking cholera outbreaks in
      Bangladesh with ingestion of saline-rich cholera-infected river water. METHODS:
      Hundred participants took part in a taste-testing experiment of water with
      varying levels of salinity. Salinity measurements were taken of both drinking and
      non-drinking water sources. Informal group discussions were conducted to gain an
      in-depth understanding of water sources and water uses. RESULTS: Salinity levels
      of non-drinking water sources suggest that the conditions for Vibrio cholerae
      survival exist 7-8 days within the local aquatic environment. However, 96% of
      participants in the taste-testing experiment reported that they would never drink
      water with salinity levels that would be conducive to V. cholerae survival.
      Furthermore, salinity levels of participant's drinking water sources were all
      well below the levels required for optimal survival of V. cholerae. Respondents
      explained that they preferred less salty and more aesthetically pleasing drinking
      water. CONCLUSION: Theoretically, V. cholerae can survive in the river systems in
      Bangladesh; however, water sources which have been contaminated with river water
      are avoided as potential drinking water sources. Furthermore, there are no
      physical connecting points between the river system and drinking water sources
      among the study population, indicating that the primary driver for cholera cases
      in Bangladesh is likely not through the contamination of saline-rich river water
      into drinking water sources.

PMID- 25581716
TI  - Perpetually self-propelling chiral single crystals.
AB  - When heated, single crystals of enantiomerically pure D- and L-pyroglutamic acid
      (PGA) are capable of recurring self-actuation due to rapid release of latent
      strain during a structural phase transition, while the racemate is mechanically
      inactive. Contrary to other thermosalient materials, where the effect is
      accompanied by crystal explosion due to ejection of debris or splintering, the
      chiral PGA crystals respond to internal strain with unprecedented robustness and
      can be actuated repeatedly without deterioration. It is demonstrated that this
      superelasticity is attained due to the low-dimensional hydrogen-bonding network
      which effectively accrues internal strain to elicit propulsion solely by elastic
      deformation without disintegration. One of the two polymorphs (beta) associated
      with the thermosalient phase transition undergoes biaxial negative thermal
      expansion (alphaa = -54.8(8) * 10(-6) K(-1), alphac = -3.62(8) * 10(-6) K(-1))
      and exceptionally large uniaxial thermal expansion (alphab = 303(1) * 10(-6) K(
      1)). This second example of a thermosalient solid with anomalous expansion
      indicates that the thermosalient effect can be expected for first-order phase
      transitions in soft crystals devoid of an extended 3D hydrogen-bonding network
      that undergo strongly anisotropic thermal expansion around the phase transition.

PMID- 25581715
TI  - Characterization of the differences in the cyclopiazonic acid binding mode to
      mammalian and P. Falciparum Ca2+ pumps: a computational study.
AB  - Despite the investments in malaria research, an effective vaccine has not yet
      been developed and the causative parasites are becoming increasingly resistant to
      most of the available drugs. PfATP6, the sarco/endoplasmic reticulum Ca2+ pump
      (SERCA) of P. falciparum, has been recently genetically validated as a potential
      antimalarial target and cyclopiazonic acid (CPA) has been found to be a potent
      inhibitor of SERCAs in several organisms, including P. falciparum. In position
      263, PfATP6 displays a leucine residue, whilst the corresponding position in the
      mammalian SERCA is occupied by a glutamic acid. The PfATP6 L263E mutation has
      been studied in relation to the artemisinin inhibitory effect on P. falciparum
      and recent studies have provided evidence that the parasite with this mutation is
      more susceptible to CPA. Here, we characterized, for the first time, the
      interaction of CPA with PfATP6 and its mammalian counterpart to understand
      similarities and differences in the mode of binding of the inhibitor to the two
      Ca2+ pumps. We found that, even though CPA does not directly interact with the
      residue in position 263, the presence of a hydrophobic residue in this position
      in PfATP6 rather than a negatively charged one, as in the mammalian SERCA,
      entails a conformational arrangement of the binding pocket which, in turn,
      determines a relaxation of CPA leading to a different binding mode of the
      compound. Our findings highlight differences between the plasmodial and human
      SERCA CPA-binding pockets that may be exploited to design CPA derivatives more
      selective toward PfATP6.

PMID- 25581712
TI  - Withholding and withdrawal of life-sustaining treatments in intensive care units
      in Asia.
AB  - IMPORTANCE: Little data exist on end-of-life care practices in intensive care
      units (ICUs) in Asia. OBJECTIVE: To describe physicians' attitudes toward
      withholding and withdrawal of life-sustaining treatments in end-of-life care and
      to evaluate factors associated with observed attitudes. DESIGN, SETTING, AND
      PARTICIPANTS: Self-administered structured and scenario-based survey conducted
      among 1465 physicians (response rate, 59.6%) who manage patients in ICUs (May
      December 2012) at 466 ICUs (response rate, 59.4%) in 16 Asian countries and
      regions. RESULTS: For patients with no real chance of recovering a meaningful
      life, 1029 respondents (70.2%) reported almost always or often withholding
      whereas 303 (20.7%) reported almost always or often withdrawing life-sustaining
      treatments; 1092 respondents (74.5%) deemed withholding and withdrawal ethically
      different. The majority of respondents reported that vasopressors, hemodialysis,
      and antibiotics could usually be withheld or withdrawn in end-of-life care, but
      not enteral feeding, intravenous fluids, and oral suctioning. For severe hypoxic
      ischemic encephalopathy after cardiac arrest, 1201 respondents (82.0% [range
      between countries, 48.4%-100%]) would implement do-not-resuscitate orders, but
      788 (53.8% [range, 6.1%-87.2%]) would maintain mechanical ventilation and start
      antibiotics and vasopressors if indicated. On multivariable analysis, refusal to
      implement do-not-resuscitate orders was more likely with physicians who did not
      value families' or surrogates' requests (adjusted odds ratio [AOR], 1.67 [95% CI,
      1.16-2.40]; P = .006), who were uncomfortable discussing end-of-life care (AOR,
      2.38 [95% CI, 1.62-3.51]; P < .001), who perceived greater legal risk (AOR, 1.92
      [95% CI, 1.26-2.94]; P = .002), and in low- to middle-income economies (AOR, 2.73
      [95% CI, 1.56-4.76]; P < .001). Nonimplementation was less likely with physicians
      of Protestant (AOR, 0.36 [95% CI, 0.16-0.80]; P = .01) and Catholic (AOR, 0.22
      [95% CI, 0.09-0.58]; P = .002) faiths, and when out-of-pocket health care
      expenditure increased (AOR, 0.98 per percentage of total health care expenditure
      [95% CI, 0.97-0.99]; P = .02). CONCLUSIONS AND RELEVANCE: Whereas physicians in
      ICUs in Asia reported that they often withheld but seldom withdrew life
      sustaining treatments at the end of life, attitudes and practice varied widely
      across countries and regions. Multiple factors related to country or region,
      including economic, cultural, religious, and legal differences, as well as
      personal attitudes, were associated with these variations. Initiatives to improve
      end-of-life care in Asia must begin with a thorough understanding of these
      factors.

PMID- 25581717
TI  - Histopathologic variation between liver lobes in dogs.
AB  - BACKGROUND: Biopsy of the liver evaluates a small portion of tissue, with
      inferences made to the entire organ. The method and number of biopsies obtained
      are tempered by consideration of the risks and benefits. Recommendations often
      include biopsy of more than one liver lobe, although the consistency of
      histopathology among lobes in dogs is unknown. HYPOTHESIS/OBJECTIVES: To describe
      the distribution of histopathologic abnormalities between liver lobes. We
      hypothesized that discordant results would be evenly distributed among all liver
      lobes. ANIMALS: Seventy dogs undergoing necropsy. METHODS: Prospective study.
      Liver samples were obtained from all lobes. A primary diagnosis was assigned to
      each liver sample based on the predominant histopathologic abnormality. RESULTS:
      In this population of dogs, biopsy of at least 2 liver lobes identified the
      predominant histologic abnormality in 98.6% of the cases. Ten (14%) of the dogs
      had <= 3 lobes in agreement and could not be assigned a predominant diagnosis.
      The same diagnosis was present in 6/6 lobes in 39 (56.5%) dogs, 5/6 lobes in 10
      (14.5%) dogs, 4/6 lobes in 10 (14.5%) dogs, 3/6 lobes in 7 (10.1%) dogs, and 2/6
      in 3 (4.3%) dogs. The number of discordant results did not differ between the
      liver lobes. CONCLUSION AND CLINICAL IMPORTANCE: The likelihood of obtaining a
      sample that is reflective of the predominant histologic abnormality in the liver
      is increased when multiple liver lobes are biopsied.

PMID- 25581718
TI  - Efficacy of inter-dental mechanical plaque control in managing gingivitis--a meta
      review.
AB  - FOCUSED QUESTION: What is the effect of mechanical inter-dental plaque removal in
      addition to toothbrushing, on managing gingivitis using various formats of inter
      dental self-care in adults based on evidence gathered from existing systematic
      reviews? MATERIAL & METHODS: Three Internet sources were searched by a strategy
      designed to include systematic reviews on inter-dental cleaning devices. Plaque
      and gingivitis scores were the primary parameters of interest. Characteristics of
      selected papers were extracted. The potential risk of bias was estimated and the
      acquired evidence was graded. RESULTS: Screening of 395 papers resulted in six
      systematic reviews. Two papers evaluated the efficacy of dental floss, two of
      inter-dental brushes (IDB), one of woodsticks and one of the oral irrigator. Weak
      evidence of unclear or small magnitude was retrieved that supported dental floss,
      woodsticks and the oral irrigator to reduce gingivitis in addition to
      toothbrushing. No concomitant evidence for an effect on plaque emerged. There is
      moderate evidence that IDBs in combination with toothbrushing reduce both plaque
      and gingivitis. CONCLUSION: Evidence suggests that inter-dental cleaning with
      IDBs is the most effective method for inter-dental plaque removal. The majority
      of available studies fail to demonstrate that flossing is generally effective in
      plaque removal. All investigated devices for inter-dental self-care seem to
      support the management of gingivitis, however, to a varying extend.

PMID- 25581719
TI  - Characteristics and significant predictors of detecting underlying diseases in
      adults with asymptomatic microscopic hematuria: a large case series of a Korean
      population.
AB  - OBJECTIVE: To provide detailed characteristics of asymptomatic microscopic
      hematuria, as well as to identify the significant predictors of detecting
      underlying diseases of asymptomatic microscopic hematuria, by evaluating a large
      Korean population. METHODS: We obtained data from healthy adults over the age of
      20 years who underwent the health-screening program from 2005 to 2010 at Seoul
      National University Bundang Hospital, resulting in 56,632 participants included
      in the analysis. Patients who had microscopic hematuria (five red blood
      cells/high-power field) were referred to a urological outpatient clinic for
      further urological evaluation. An underlying disease of asymptomatic microscopic
      hematuria was predefined as a urinary stone, renal mass, urothelial cancer or
      other relevant lesions. RESULTS: At the initial urinalysis, 6.2% (3517/56,632)
      were diagnosed with asymptomatic microscopic hematuria. Of these, 1619
      participants underwent repeat urinalysis within 1 year after screening, and 911
      (56.3%) participants were detected with microscopic hematuria again. We
      identified 131 lesions (3.7%) as underlying diseases for asymptomatic microscopic
      hematuria, with urinary stone as the most common cause. Just six lesions were
      malignant: three renal cell carcinomas and three bladder cancers. Male sex and
      diabetes mellitus were significant predictors for detection of underlying
      diseases of asymptomatic microscopic hematuria. CONCLUSIONS: Herein we report the
      largest screening case series of asymptomatic microscopic hematuria including
      approximately 60,000 asymptomatic participants studied at a single institution.
      These findings provide clinical practice information for the management of
      asymptomatic microscopic hematuria in adults.

PMID- 25581720
TI  - Uniform, stable, and efficient planar-heterojunction perovskite solar cells by
      facile low-pressure chemical vapor deposition under fully open-air conditions.
AB  - Recently, hybrid perovskite solar cells (PSCs) have attracted extensive attention
      due to their high efficiency and simple preparing process. Herein, a facile low
      pressure chemical vapor deposition (LPCVD) technology is first developed to
      fabricate PSCs, which can effectively reduce the over-rapid intercalating
      reaction rate and easily overcome this blocking issue during the solution
      process. As a result, the prepared uniform perovskite films exhibit good
      crystallization, strong absorption, and long carrier diffusion length. More
      strikingly, CH3NH3PbI3 absorbers by LPCVD demonstrate excellent moisture
      resistant feature even under laser illumination and high-temperature conditions,
      which indicates that our proprietary method is very suitable for the future low
      cost, nonvacuum production of the new generation photovoltaic devices. Finally,
      high efficiency of 12.73% is successfully achieved under fully open-air
      conditions. To the best of our knowledge, this is the first report of efficient
      PSCs with such a high humidity above 60%. 

PMID- 25581721
TI  - Depth shapes alpha- and beta-diversities of microbial eukaryotes in surficial
      sediments of coastal ecosystems.
AB  - Little is known about the relative influence of historic processes and
      environmental gradients on shaping the diversity of single-celled eukaryotes in
      marine benthos. By combining pyrosequencing of 18S ribosomal RNA genes with data
      on multiple environmental factors, we investigated the diversity of
      microeukaryotes in surficial sediments of three basins of the Yellow Sea Large
      Marine Ecosystem. A considerable proportion (about 20%) of reads was affiliated
      with known parasitoid protists. Dinophyta and Ciliophora appeared dominant in
      terms of relative proportion of reads and operational taxonomic unit (OTU)
      richness. Overall, OTU richness of benthic microeukaryotes decreased with
      increasing water depth and decreasing pH. While community composition was
      significantly different among basins, partial Mantel tests indicated a depth
      decay pattern of community similarity, whereby water depth, rather than
      geographic distance or environment, shaped beta-diversity of benthic
      microeukaryotes (including both the abundant and the rare biosphere) on a
      regional scale. Similar hydrographic and mineralogical factors contributed to the
      biogeography of both the abundant and the rare OTUs. The trace metal vanadium had
      a significant effect on the biogeography of the rare biosphere. Our study sheds
      new light on the composition, diversity patterns and underlying mechanisms of
      single-celled eukaryote distribution in surficial sediments of coastal oceans. 

PMID- 25581722
TI  - Plant stomatal closure improves aphid feeding under elevated CO2.
AB  - Stomata help plants regulate CO2 absorption and water vapor release in response
      to various environmental changes, and plants decrease their stomatal apertures
      and enhance their water status under elevated CO2 . Although the bottom-up effect
      of elevated CO2 on insect performance has been extensively studied, few reports
      have considered how insect fitness is altered by elevated CO2 -induced changes in
      host plant water status. We tested the hypothesis that aphids induce stomatal
      closure and increase host water potential, which facilitates their passive
      feeding, and that this induction can be enhanced by elevated CO2 . Our results
      showed that aphid infestation triggered the abscisic acid (ABA) signaling pathway
      to decrease the stomatal apertures of Medicago truncatula, which consequently
      decreased leaf transpiration and helped maintain leaf water potential. These
      effects increased xylem-feeding time and decreased hemolymph osmolarity, which
      thereby enhanced phloem-feeding time and increased aphid abundance. Furthermore,
      elevated CO2 up-regulated an ABA-independent enzyme, carbonic anhydrase, which
      led to further decrease in stomatal aperture for aphid-infested plants. Thus, the
      effects of elevated CO2 and aphid infestation on stomatal closure synergistically
      improved the water status of the host plant. The results indicate that aphid
      infestation enhances aphid feeding under ambient CO2 and that this enhancement is
      increased under elevated CO2 .

PMID- 25581723
TI  - The eukaryotic way to defend and edit genomes by sRNA-targeted DNA deletion.
AB  - While there is currently burgeoning interest in the application of the CRISPR/Cas
      (clustered regularly interspaced short palindromic repeats/CRISPR-associated
      genes) to genome editing, it is perhaps not widely appreciated that this is the
      second discovery of a small RNA (sRNA)-targeted DNA-deletion system. The first
      sRNA-targeted DNA-deletion system to be discovered, which we call IES/Ias
      (internal eliminated sequence/IES-associated genes) to contrast with CRISPR/Cas,
      is found in ciliates, and, like CRISPR/Cas, is thought to serve as a form of
      immune defense against invasive DNAs. The manner in which the ciliate IES/Ias
      system functions is distinct from that of the CRISPR/Cas system in archaea and
      bacteria, and arose independently through a synthesis of RNA interference-derived
      and DNA-specific molecular components. Despite the major differences between
      CRISPR/Cas and IES/Ias, both systems face similar conceptual challenges in
      targeting invasive DNAs. In this review, we focus on the discovery, effects,
      function, and evolutionary consequences of the IES/Ias system.

PMID- 25581724
TI  - Patient-provider communication over social media: perspectives of adolescents
      with psychiatric illness.
AB  - BACKGROUND: Social media is an increasingly dominant platform for communication,
      especially among adolescents. Statements from professional bodies and a growing
      body of empirical evidence support a role for social media in improving provider
      patient interactions. In psychiatry, particular concerns exist about the
      suitability of this style of communication. Very limited data are available
      exploring how patients would like to incorporate social media into their
      communication with their psychiatric providers. METHODS: We conducted a
      qualitative study with 20 adolescents attending the Yale Psychiatric Hospital
      Intensive Outpatient Programme. Interviews were analysed using inductive thematic
      analysis. RESULTS: Participants highlighted how social media could allow for
      constant access to a mental health provider, provide a less anxiety-provoking
      mode of communication, and allow for them to be monitored in a more on-going
      fashion. However, participants also identified many potential risks associated
      with these applications, including the potential for anxiety if a provider was
      not able to respond immediately, and a sense that online interactions would be
      less rich overall. DISCUSSION: Our findings suggest that adolescents are open to
      the idea of communicating with mental health providers over social media and are
      able to describe a number of instances where this could be of value. The risks
      participants described, as well as concerns raised by existing literature,
      indicate the need for further work and protocol development in order for social
      media to be a feasible tool for communication between providers and adolescents
      with psychiatric illness.

PMID- 25581725
TI  - Synthesis, characterisation and properties of rare earth oxyselenides A4O4Se3 (A
      = Eu, Gd, Tb, Dy, Ho, Er, Yb and Y).
AB  - Rare earth oxyselenides A4O4Se3 (A = Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb and Y)
      were synthesised using solid state reactions and three new structure types (beta,
      gamma, and delta) were observed. A4O4Se3 materials adopt either the alpha (A =
      Nd, Sm), beta (A = Eu), gamma (A = Gd, Tb) or delta (A = Dy, Ho, Er, Yb, Y)
      structure depending on the rare earth radius. Each structure type contains
      alternating [A2O2](2+) and Se(2-)/Se2(2-) layers. Different ordered and
      disordered arrangements of Se(2-) and [Se-Se](2-) give the Se layer flexibility
      and lead to the four different structure types observed. The volume coefficients
      of expansion for A4O4Se3 ranged from +1.746(9) * 10(-5) to +2.237(3) * 10(-5) K(
      1) from 12 to 300 K; no structural phase transitions were observed in this
      temperature range. Diffuse reflection spectra show A4O4Se3 are semiconductors
      with band gap Eg 1.02-1.46 eV. Gd4O4Se3, Dy4O4Se3, and Tb4O4Se3 samples show
      antiferromagnetic ordering with Neel temperature, TN, of 7-9 K. DFT calculations
      confirm the two different valence states of Se(2-) and Se2(2-) in Eu4O4Se3. 

PMID- 25581726
TI  - Notice of concern: Re: Thakur A, Kadam RS, and Kompella UB (2011) Influence of
      drug solubility and lipophilicity on transscleral retinal delivery of six
      corticosteroids. Drug Metab Dispos 39:771-781; doi:10.1124/dmd.110.037408.

PMID- 25581727
TI  - BRAF VE1 immunoreactivity patterns in epithelioid glioblastomas positive for BRAF
      V600E mutation.
AB  - Epithelioid glioblastomas (E-GBMs) manifest BRAF V600E mutation in up to 50% of
      cases, compared with a small percentage of ordinary GBMs, suggesting that they
      are best considered variants rather than a different pattern of GBM. Availability
      of a targeted therapy, vemurafenib, may make testing BRAF status important for
      treatment. It is unclear whether BRAF VE1 immunohistochemistry (IHC) can
      substitute for Sanger sequencing in these tumors. BRAF VE1 IHC was correlated
      with Sanger sequencing results on our original cohort of E-GBMs, and then new E
      GBM cases were tested with both techniques (n=20). Results were compared with
      those in similarly assessed giant cell GBMs, anaplastic pleomorphic
      xanthoastrocytomas. All tumors tested showed 1:1 correlation between BRAF V600E
      mutational results and IHC. However, heavy background immunostaining in some
      negatively mutated cases resulted in equivocal results that required repeat IHC
      testing and additional mutation testing using a different methodology to confirm
      lack of detectable BRAF mutation. Mutated/BRAF VE1 IHC E-GBMs and anaplastic
      pleomorphic xanthoastrocytomas tended to manifest strong, diffuse cytoplasmic
      immunoreactivity, compared with previously studied gangliogliomas, which
      demonstrate more intense immunoreactivity in the ganglion than in the glial tumor
      component. One of our E-GBM patients with initial gross total resection quickly
      recurred within 4 months, required a second resection, and then was placed on
      vemurafenib; she remains tumor free 21 months after second resection without
      neuroimaging evidence of residual disease, adding to the growing number of
      reports of successful treatment of BRAF-mutated glial tumors with drug. E-GBMs
      show good correlation between mutational status and IHC, albeit with limitations
      to IHC. E-GBMs can respond to targeted therapy. 

PMID- 25581728
TI  - Clear cell myoepithelial carcinoma of salivary glands showing EWSR1
      rearrangement: molecular analysis of 94 salivary gland carcinomas with prominent
      clear cell component.
AB  - This study examines the presence of the EWSR1 rearrangement in a variety of clear
      cell salivary gland carcinomas with myoepithelial differentiation. A total of 94
      salivary gland carcinomas with a prominent clear cell component included 51 cases
      of clear cell myoepithelial carcinomas de novo (CCMC), 21 cases of CCMCs ex
      pleomorphic adenoma (CCMCexPA), 11 cases of epithelial-myoepithelial carcinoma
      (EMC), 6 cases of EMC with solid clear cell overgrowth, and 5 cases of
      hyalinizing clear cell carcinoma of minor salivary glands. In addition, 10 cases
      of myoepithelial carcinomas devoid of clear cell change and 12 cases of benign
      myoepithelioma were included as well. All the tumors in this spectrum were
      reviewed, reclassified, and tested by fluorescence in situ hybridization (FISH)
      for the EWSR1 rearrangement using the Probe Vysis EWSR1 Break Apart FISH Probe
      Kit. The EWSR1 rearrangement was detected in 20 of 51 (39%) cases of CCMC, in 5
      of 21 (24%) cases of CCMCexPA, in 1 of 11 (9%) cases of EMC, and in 4 of 5 (80%)
      cases of hyalinizing clear cell carcinoma. The 25 EWSR1-rearranged CCMCs and
      CCMCexPAs shared similar histomorphology. They were arranged in nodules composed
      of compact nests of large polyhedral cells with abundant clear cytoplasm.
      Necrosis, areas of squamous metaplasia, and hyalinization were frequent features.
      Immunohistochemically, the tumors expressed p63 (96%), cytokeratin CK14 (96%),
      and S100 protein (88%). MIB1 index varied from 10% to 100%, with most cases in
      the 20% to 40% range. Clinical follow-up information was available in 21 cases
      (84%) and ranged from 3 months to 15 years (mean 5.2 y); 4 patients were lost to
      follow-up. Ten patients are alive with no evidence of recurrent or metastatic
      disease in the follow-up period from 3 months to 15 years (mean 5 y), 3 patients
      are alive with recurrent and metastatic disease, and 8 died of disseminated
      cancer 9 months to 16 years after diagnosis (mean 6 y). Lymph node metastasis
      appeared in 5 patients within 5 months to 4 years after diagnosis (mean 22 mo),
      distant metastases were noted in 7 patients with invasion of orbit (2 cases), and
      in 1 case each metastasis to the neck soft tissues, liver, lungs, mediastinum,
      and thoracic vertebra was noted. We describe for the first time EWSR1 gene
      rearrangement in a subset of myoepithelial carcinomas arising in minor and major
      salivary glands. The EWSR1-rearranged CCMC represents a distinctive aggressive
      variant composed predominantly of clear cells with frequent necrosis. Most EWSR1
      rearranged CCMCs of salivary glands are characterized by poor clinical outcomes. 

PMID- 25581729
TI  - Myogenic differentiation and histologic grading are major prognostic determinants
      in retroperitoneal liposarcoma.
AB  - The aim of the present work was to improve the understanding of the impact of
      malignancy grade and myogenic/rhabdomyoblastic differentiation on the natural
      course of retroperitoneal liposarcoma. All consecutive patients affected by
      primary well-differentiated (WD)/dedifferentiated (DD) retroperitoneal
      liposarcoma, surgically treated at our institution between January 2002 and
      December 2011, were retrospectively evaluated. Tumors were stained for mdm2 and 5
      myogenic markers (smooth muscle actin-alpha, h-caldesmon, calponin, desmin,
      myogenin). The French National Federation of the Centers for the Fight Against
      Cancer (FNCLCC) grading system was applied. Overall survival, crude cumulative
      incidence of local recurrence, and distant metastases were calculated.
      Multivariable analyses were carried out. A total of 144 patients were identified.
      Median follow-up was 68 months (interquartile range: 46 to 104 mo). Fifty-two
      patients were affected by WD/G1 and 92 by DD liposarcoma. Among the latter, 60
      were grade G2 and 32 G3. Myogenic differentiation was present in 54 cases (8/52
      WD/G1, 27/60 DD/G2, 18/32 DD/G3). Seven cases had a rhabdomyoblastic DD component
      (1/60 DD/G2 and 6/32 DD/G3). Five-year overall survival rates were 93%, 57%, and
      21% for WD/G1 liposarcoma, G2 DD, and G3 DD liposarcoma, respectively, and 75%,
      42%, and 29% for liposarcoma without myogenic differentiation, with myogenic
      differentiation, with rhabdomyoblastic differentiation, respectively (P<0.001).
      Of note, 5/6 patients affected by G3 DD liposarcoma with a rhabdomyoblastic
      component died within 8 months. FNCLCC grade and myogenic differentiation
      significantly predicted the outcome of retroperitoneal liposarcoma. These should
      be factored into treatment decision-making and possibly used to stratify patients
      in clinical trials. 

PMID- 25581730
TI  - Expression profiles of MYC protein and MYC gene rearrangement in lymphomas.
AB  - MYC translocations are a defining feature of Burkitt lymphoma and a group of
      diffuse large B-cell lymphoma (DLBCL) with inferior outcome. However, the
      clinical relevance of MYC gene rearrangement and its relationship with MYC
      protein expression has not been well characterized in lymphomas. Tissue
      microarrays containing 1214 lymphomas were successfully evaluated by
      immunohistochemistry using anti-MYC clone Y69 and a dual-color break-apart
      fluorescence in situ hybridization probe to detect MYC gene rearrangements.
      Aggressive B-cell lymphomas including Burkitt lymphoma and DLBCL showed the
      highest level of MYC protein staining defined as staining in >50% of lymphoma
      cells. A significant proportion of plasmablastic, B-lymphoblastic and T
      lymphoblastic, and extranodal NK/T-cell lymphomas also showed staining in >50% of
      cells, whereas only occasional plasma cell myeloma, mantle cell lymphoma, and
      classical Hodgkin lymphoma showed a high level of staining. Small B-cell
      lymphomas, when positive, showed MYC protein in <50% of cells. In aggressive B
      cell lymphomas, MYC rearrangement and MYC immunohistochemistry showed a high
      concordance rate; however, some DLBCL and all T-cell and NK-cell lymphomas with
      MYC protein expression lacked MYC gene rearrangements. Our results provide a
      baseline for MYC protein expression in lymphomas and indicate that its expression
      is not specific to lymphoma subtypes, cell lineage, or expected clinical behavior
      and is highly variable. In addition, MYC protein expression is not necessarily
      correlated with MYC gene rearrangements and suggests the need for caution in the
      interpretation of MYC immunohistochemistry in the differential diagnosis of
      lymphomas. 

PMID- 25581731
TI  - FOXL2 mutation is absent in uterine tumors resembling ovarian sex cord tumors.
AB  - Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare uterine
      neoplasms characterized by pure or predominant epithelial-like patterns that
      share morphologic, immunohistochemical, and ultrastructural features with ovarian
      sex cord tumors. FOXL2 immunoexpression has recently been found in sex cord
      stromal tumors of the ovary, including granulosa cell tumors, Sertoli-Leydig cell
      tumors, thecomas, and fibromas, but mutations have been identified mostly in
      adult granulosa cell tumors. In this study, we investigated FOXL2 mutation status
      and protein expression in UTROSCTs. Mutational analysis using a TaqMan real-time
      polymerase chain reaction-based allelic discrimination assay was performed on
      formalin-fixed, paraffin-embedded tissue from 15 UTROSCTs. FOXL2 mutation was
      absent in all tumors. FOXL2 immunoexpression was tested in all 15 tumors.
      Intensity of staining was scored as weak, moderate, or strong. Percentage of
      tumor cells with nuclear staining was recorded as follows: 0 (negative); 1+ (1%
      to 25%); 2+ (26% to 50%); 3+ (51% to 75%); and 4+ (76% to 100%). Nuclear
      expression of FOXL2 was present in 6 of 15 (40%) UTROSCTs. One tumor demonstrated
      strong 4+ staining. Moderate expression was seen in 3 cases, including 2 and 1
      showing 2+ and 1+ staining, respectively. Weak expression was observed in 2
      tumors demonstrating 3+ and 1+ staining. Although UTROSCTs show overlapping
      morphologic, immunohistochemical, and ultrastructural features with sex cord
      stromal tumors of the ovary, they do not harbor FOXL2 mutation despite focal
      immunoreactivity in a subset of these tumors. 

PMID- 25581732
TI  - Evidence for a dualistic model of high-grade serous carcinoma: BRCA mutation
      status, histology, and tubal intraepithelial carcinoma.
AB  - Most early adnexal carcinomas detected in asymptomatic women with germline BRCA
      mutations (BRCA) present as serous tubal intraepithelial carcinomas (STIC).
      However, STICs are found in only ~40% of symptomatic high-grade serous carcinomas
      (HGSCs) and less frequently in pseudoendometrioid variants of HGSC. Consecutive
      cases of untreated HGSC from BRCA and BRCA women with detailed fallopian tube
      examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined,
      and tumors were classified morphologically as SET ("SET", >50% solid,
      pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET
      tumors trended toward a higher frequency in BRCA versus BRCA women (50% vs. 28%,
      P=0.11), had a significantly younger mean age than those with classic HGSC in
      BRCA women (mean 56.2 vs. 64.8 y, P=0.04), and displayed a better clinical
      outcome in both groups combined (P=0.024). STIC was significantly more frequent
      in tumors from the BRCA cohort (66% vs. 31%, P=0.017) and specifically the BRCA
      tumors with classic morphology (83%) versus those with SET morphology (22%,
      P=0.003). Overall, several covariables-histology, BRCA status, age, coexisting
      STIC, and response to therapy-define 2 categories of HGSC with differences in
      precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic
      HGSC model that could shed light on the differences in frequency of STIC between
      symptomatic and asymptomatic women with HGSC. This model emphasizes the need for
      further study of HGSC precursors to determine their relevance to the prevention
      of this lethal malignancy. 

PMID- 25581733
TI  - The number and distribution of eosinophils in the adult human gastrointestinal
      tract: a study and comparison of racial and environmental factors.
AB  - There are surprisingly limited data regarding normal counts or distribution of
      eosinophils in the gastrointestinal tract, despite the increasing incidence of
      eosinophilic gastrointestinal tract diseases. Moreover, there are no published
      reports on the eosinophil number throughout the gastrointestinal tract of adults
      or Asian populations, or those investigating the effect of race on eosinophil
      count. First, in our study, the number of eosinophils from each portion of the
      gastrointestinal mucosa was quantified on biopsy slides from a Japanese adult
      population (132 samples). Next, the surgical resections from Japanese (110
      samples), Japanese Americans (64), and Caucasians (57) were used to investigate
      the racial and environmental effects. Our results with the Japanese biopsy
      samples showed a significant increase in the number of eosinophils from the
      esophagus to the right colon (mean+/-SD/mm: 0.07+/-0.43 for the esophagus,
      12.18+/-11.39 for the stomach, and 36.59+/-15.50 for the right colon), compared
      with a decrease in the left colon (8.53+/-7.83). Investigation using surgical
      samples showed that the distribution patterns in the gastrointestinal tract were
      very similar among the 3 ethnic groups, and there were no significant differences
      in the number of eosinophils among these groups, except in the esophageal
      epithelium. This study is the first report on the normal numbers and distribution
      of eosinophils throughout the gastrointestinal tract not only of an Asian
      population but also of adults. Our data suggest that a cutoff value for
      eosinophil counts, when rendering a diagnosis of eosinophilic gastrointestinal
      tract disease, should be individualized to the different biopsy sites.
      Interestingly, race and environmental factors did not seem to have a significant
      effect on eosinophil densities and distributions. 

PMID- 25581734
TI  - Brief fixation and hormone receptor expression in breast cancer.

PMID- 25581735
TI  - Brief fixation and hormone receptor expression in breast cancer: authors' reply.

PMID- 25581736
TI  - Synthesis of a graphene-based nanocomposite for the dispersive solid-phase
      extraction of vancomycin from biological samples.
AB  - The approach of this work was to study the capability of graphene-based materials
      in the field of biological sample preparation. A polypyrrole/graphene composite
      was synthesized and characterized. The potential of the nanocomposite was
      investigated as a sorbent in dispersive solid-phase extraction followed by high
      performance liquid chromatography with UV detection for vancomycin as a model
      drug. The effect of different parameters influencing extraction efficiency such
      as sample pH and sample volume, ionic strength, extraction time, type, and volume
      of desorption solvent and desorption time were investigated. A comparison study
      was also conducted between polypyrrole/graphene and some different novel and
      classic sorbents. Under optimized conditions, the calibration curve for
      vancomycin showed linearity in the range of 0.05-10 MUg/mL. In addition, limits
      of detection, and quantification were 0.003 and 0.01 MUg/mL, respectively. The
      intraday and interday relative standard deviations at a concentration of 0.05
      MUg/mL (n = 3) were 1.6 and 2.1%, respectively. Furthermore, the proposed method
      was successfully applied for the determination of vancomycin in plasma and urine
      samples. The relative recoveries indicated the feasibility of graphene-based
      sorbents in biological sample analysis. 

PMID- 25581737
TI  - Hepatocyte responses to in vitro freezing and beta-adrenergic stimulation:
      Insights into the extreme freeze tolerance of subarctic Rana sylvatica.
AB  - The wood frog, Rana sylvatica LeConte 1825, is a freeze-tolerant amphibian widely
      distributed in North America. Subarctic populations of this species can survive
      experimental freezing to temperatures below -16  degrees C, whereas temperate
      populations tolerate freezing only at temperatures above -6  degrees C. We
      investigated whether hepatocytes isolated from frogs indigenous to Interior
      Alaska (subarctic) or southern Ohio (temperate) had distinct characteristics that
      could contribute to this variation in freeze tolerance capacity. Following in
      vitro freezing, cell damage, as assessed from lactate dehydrogenase leakage, was
      similar between samples from Alaskan and Ohioan frogs. Preincubation of cells in
      media containing glucose or urea, the two primary cryoprotectants used by R.
      sylvatica, markedly reduced freezing damage to hepatocytes; however, results
      suggested that cells of the northern phenotype were comparatively more amenable
      to cryoprotection by urea. Stimulation of isolated hepatocytes with beta
      adrenergic agonists, which simulates the freezing-induced cryoprotectant
      mobilization response, gave rates of glucose production from endogenous glycogen
      reserves that were similar between the populations. Our findings suggest that
      extreme freeze tolerance in subarctic R. sylvatica does not require an enhanced
      ability of the liver to resist freezing stress or rapidly mobilize
      cryoprotectant.

PMID- 25581738
TI  - Bet3 participates in autophagy through GTPase Ypt1 in Saccharomyces cerevisiae.
AB  - Three TRAPP (transport protein particle) complexes have been identified in
      Saccharomyces cerevisiae. GTPases Ypt1 and Ypt31/32 suppress autophagic defects
      in the mutants of TRAPPIII-specific subunit (Trs85) and TRAPPII-specific subunits
      (Trs130 and Trs120), respectively. However, the roles of the common TRAPP
      subunits (which also form the TRAPPI complex) in autophagy and their relationship
      to Rab GTPases in autophagy remain unclear. As Bet3 (a common TRAPP subunit)
      cannot be mutated together with either Trs85 or Trs130, we examined starvation
      induced autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway in bet3ts
      cells. The results demonstrated that GFP-Atg8 was dispersed in the cytoplasm and
      Ape1 accumulated as a unique dot on the vacuolar membrane in bet3ts cells.
      Further analysis revealed that Ape1 maturation and GFP-Atg8 processing are
      defective in these cells. However, prApe1 (precursor form of Ape1) and GFP-Atg8
      are protease-accessible in bet3ts cells under starvation, which indicates that
      Bet3 functions before autophagosome closure. Furthermore, active Ypt1, but not
      Ypt31, partly rescued the autophagic defects of bet3ts cells. We conclude that
      Bet3 is involved in autophagy and propose that it participates in autophagy
      through TRAPP complexes mostly via Ypt1 in yeast. 

PMID- 25581739
TI  - Effect of angular stability and other locking parameters on the mechanical
      performance of intramedullary nails.
AB  - To extend the indications of intramedullary nails for distal or proximal
      fractures, nails with angle stable locking options have been developed. Studies
      on the mechanical efficacy of these systems have been inconsistent likely due to
      confounding variables such as number, geometry, or orientation of the screws, as
      well as differences in the loading mode. Therefore, the aim of this study was to
      quantify the effect of angular stability on the mechanical performance of
      intramedullary nails. The results could then be compared with the effects of
      various locking screw parameters and loading modes. A generic model was developed
      consisting of artificial bone material and titanium intramedullary nail that
      provided the option to systematically modify the locking screw configuration.
      Using a base configuration, the following parameters were varied: number of
      screws, distance and orientation between screws, blocking of screws, and
      simulation of freehand locking. Tension/compression, torsional, and bending loads
      were applied. Stiffness and clearance around the zero loading point were
      determined. Angular stability had no effect on stiffness but completely blocked
      axial clearance (p=0.003). Simulation of freehand locking reduced clearance for
      all loading modes by at least 70% (p<0.003). The greatest increases in torsional
      and bending stiffness were obtained by increasing the number of locking screws
      (up to 80%, p<0.001) and by increasing the distance between them (up to 70%,
      p<0.001). In conclusion, our results demonstrate that the mechanical performance
      of IM nailing can be affected by various locking parameters of which angular
      stability is only one. While angular stability clearly reduces clearance of the
      screw within the nail, mechanical stiffness depends more on the number of screws
      and their relative distance. Thus, optimal mechanical performance in IM nailing
      could potentially be obtained by combining angular stability with optimal
      arrangement of locking screws. 

PMID- 25581740
TI  - Prophylactic bioactive screw fixation as an alternative augmentation for
      femoroplasty.
AB  - Femoroplasty is theoretically a prophylactic surgical procedure for femoral neck
      fracture. Although bone cement is generally used for augmentation, its
      distribution cannot be easily controlled. This study investigated whether a
      bioactive screw is feasible for femoroplasty as an alternative augmentation
      material. A mechanical test was done to compare the strength of four types of
      augmentation bioactive screw (Superfixsorb), two bioinert cements, or no
      intervention in a composite femoral bone. The peak load to fracture under
      simulated falling was compared among the four groups. The mean peak load to
      failure in the bioactive screw group (2667 N) was significantly higher than that
      in the intact group (2391 N) (p=0.028), comparable to that in the Simplex P
      cement group (2864 N) (p=0.11), and significantly lower than that of the
      cranioplastic cement group (3022 N) (p=0.006). The strength of a composite femur
      with the bioactive screw was higher than that of an intact bone and comparable to
      one cement augmentation. Thus, this bioactive screw can be potentially used as
      augmentation material for femoroplasty. 

PMID- 25581741
TI  - Hyperthyroidism hidden by congenital central hypoventilation syndrome.
AB  - Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy
      with severe central hypoventilation. CCHS results from a mutation in the paired
      like homeobox 2B gene (PHOX2B). In addition to hypoventilation, patients with
      CCHS display a wide array of autonomic nervous system abnormalities, including
      decreased heart rate variability and abrupt sinus pauses, esophageal dysmotility,
      abnormal pupillary light response, and temperature dysregulation, to name a few.
      To date, there has been no documentation of a child with both CCHS and
      hyperthyroidism. We report the case of a young child with CCHS who presented with
      tachycardia, which was later found to be due to Grave's disease, after many
      months of investigation. 

PMID- 25581742
TI  - Hashimoto's encephalopathy: a rare pediatric brain disease.
AB  - We report a 9-year-old female who presented with new onset intractable seizure
      activity followed by a prolonged encephalopathic state. After ruling out common
      etiologies, Hashimoto's encephalopathy (HE) was considered, and antibody levels
      to thyroid peroxidase and thyroglobulin were both markedly elevated in her serum.
      She was euthyroid at the time of presentation. Upon treatment with high dose
      methylprednisolone, the patient demonstrated a significant improvement in her
      encephalopathy. The diagnosis of HE requires strong clinical suspicion with
      evidence of antithyroid antibodies, as well as an encephalopathy not explained by
      another etiology. While well documented in the adult literature, only a handful
      of pediatric cases have been described to date. Patients with HE have a nearly
      universal response to high dose glucocorticoids. HE should be considered in the
      differential diagnosis of any patient, adult or pediatric, who displays
      prolonged, unexplainable encephalopathy. 

PMID- 25581743
TI  - The prevalence of vitamin D deficiency among schoolchildren: a cohort study from
      Xinxiang, China.
AB  - AIM: Vitamin D deficiency (VDD) in children is widespread. Therefore, the present
      study was conducted to assess the prevalence of VDD in schoolchildren from Henan
      Province, China. METHODS: The study was conducted on school students from areas
      of Xinxiang, one of the largest cities of Henan Province in China, in the winter
      of 2013. A questionnaire on demographic data, socioeconomic status, sun exposure,
      and times of acute respiratory infections (RTI) in the past 12 months were
      completed for each student. Blood samples were taken to assess serum levels of 25
      hydroxyvitamin D [25(OH)D]. RESULTS: In our study, 606 schoolchildren completed
      the questionnaire. The median serum level of 25(OH)D was 20.5 ng/mL
      (interquartile range: 15.9-25.1). The prevalence of VDD and insufficiency was
      46.9% (284/606) and 85.8% (520/606), respectively. VDD was more associated with
      female gender, high body mass index, lower socio-professional status, residence
      in urban areas, and less time spent outdoors. There was an inverse correlation
      between levels of 25(OH) and times of RTI (p<0.001). CONCLUSION: VDD and
      insufficiency are common among schoolchildren in Xinxiang. Supplementation with
      food fortification or vitamin D for Chinese children is warranted.

PMID- 25581744
TI  - The use of pamidronate for acute vitamin D intoxication, clinical experience with
      three cases.
AB  - Vitamin D intoxication in infancy has serious consequences attributable to acute
      hypercalcemia and subsequent hypercalcuria or nephrocalcinosis. Traditonal
      treatment methods is inadequate in some patients with severe hypercalcemia due to
      vitamin D intoxication. Our experience suggests that bisphosphonates may be an
      effective and reliable drug in the treatment of severe and persistant
      hypercalcemia. 

PMID- 25581745
TI  - The c.301_302delAG PROP1 gene mutation in Romanian patients with multiple
      pituitary hormone deficiency.
AB  - OBJECTIVE: To establish the frequency of the c.301_302 delAG mutation of the
      PROP1 gene in Romanian patients with multiple pituitary hormone deficiency
      (MPHD). SUBJECTS AND METHODS: Somatic assessment, hormonal test, bone age,
      magnetic resonance imaging of the pituitary gland, and molecular diagnosis were
      performed in 26 patients with MPHD (7 patients with familial form of MPHD and 19
      patients with sporadic form of MPHD). RESULTS: The c.301_302delAG mutation was
      detected in the homozygous state in 10 patients belonging to 5 unrelated families
      (7 patients with familial history of MPHD and 3 patients with sporadic form of
      MPHD). Those 10 patients presented variable pituitary hormone deficiency and
      pituitary morphology. CONCLUSIONS: The c.301_302delAG homozygous genotype had a
      high frequency of 38% (10/26), reaching 100% (7/7) in group with familial cases
      of MPHD and 16% (3/19) in group with sporadic forms of MPHD.

PMID- 25581746
TI  - Cognitive functioning, metabolic control, and treatment type in youth with type 1
      diabetes.
AB  - BACKGROUND: There is growing evidence that cognitive functioning plays an
      important role in self-care behavior and glycemic control in pediatric patients
      with type 1 diabetes. The aim of this pilot study was to examine whether there
      were differences in glycemic control and cognitive functioning between youth with
      T1D treated with continuous subcutaneous insulin infusion and multiple daily
      injections. METHODS: The sample consisted of 29 youth diagnosed with type 1
      diabetes ages 6-15 years (mean age=11.72 years) receiving care at an outpatient
      pediatric endocrinology clinic. Youth were administered the Wechsler Abbreviated
      Scale of Intelligence and Wide Range Assessment of Memory and Learning.
      Independent samples t-tests were used to compare youth with T1D treated with MDI
      vs. CSII on glycemic control, verbal memory, visual memory,
      attention/concentration, and intelligence. RESULTS: Mean intelligence scores for
      the insulin pump sample were higher than the daily injection sample. This
      difference was a medium to large effect. After controlling for demographic
      variables, age of onset for diabetes, and glycemic control, treatment type was
      still a significant predictor of intelligence demonstrating that CSII was
      associated with higher intelligence scores. CONCLUSION: The use of standardized
      measures of cognitive functioning in routine clinical care may shed some light on
      the complex interplay between cognitive functioning, treatment type, and glycemic
      control when managing pediatric patients with T1D.

PMID- 25581747
TI  - An increasing incidence of type 1 diabetes mellitus in Romanian children aged 0
      to 17 years.
AB  - BACKGROUND: The epidemiology of type 1 diabetes mellitus may provide insights
      into the pathogenesis of the disease. OBJECTIVE: The aim of this work was to
      characterize the trend of the incidence of type 1 diabetes mellitus in Romanian
      children aged from 0 to 17 years over a 10-year interval. SUBJECTS AND METHODS:
      Data regarding new cases were obtained from two sources: (1) The Romanian
      Childhood Diabetes Registry and (2) Records of the Medical Center "Cristian
      Serban", Buzias. The demographic data were retrieved from the National Institute
      for Statistics. The incidence was calculated for the age groups 0-4, 5-9, 10-14,
      and 15-17 years. RESULTS: A total of 3196 new cases, aged below 18 years, were
      found by both the sources. There were significant differences between the groups
      (p=0.012), the mean incidence being highest in the age group 10-14 years
      (9.6/100,000/year, 95% CI 9-10.1) and lowest in children aged from 0 to 4 years
      (4.8/100,000/year, 95% CI 4.4-5.3). Boys were slightly more frequently affected
      than girls (p=0.038). The age and gender adjusted incidence of type 1 diabetes
      mellitus increased significantly (p<0.001) from 6.2/100,000/year (95% CI 5.5-6.9)
      in 2002 to 9.3/100,000/year (95% CI 8.4-10.3) in 2011. The raise in incidence was
      noticed in all age groups except for 15-17 years. CONCLUSION: Romania is a
      country with an intermediate incidence of type 1 diabetes mellitus in children,
      which is slightly higher in boys than in girls. The incidence of type 1 diabetes
      mellitus increased continuously during the 10-year survey, with the exception of
      the oldest teens.

PMID- 25581748
TI  - Maturity-onset diabetes of the young (MODY): an update.
AB  - Maturity-onset diabetes of the young (MODY) is a group of monogenic disorders
      characterized by autosomal dominantly inherited non-insulin dependent form of
      diabetes classically presenting in adolescence or young adults before the age of
      25 years. MODY is a rare cause of diabetes (1% of all cases) and is frequently
      misdiagnosed as Type 1 diabetes (T1DM) or Type 2 diabetes (T2DM). A precise
      molecular diagnosis is essential because it leads to optimal treatment of the
      patients and allows early diagnosis for their asymptomatic family members.
      Mutations in the glucokinase (GCK) (MODY 2) and hepatocyte nuclear factor
      (HNF)1A/4A (MODY 3 and MODY 1) genes are the most common causes of MODY. GCK
      mutations cause a mild, asymptomatic, and stable fasting hyperglycemia usually
      requiring no specific treatment. However, mutations in the HNF1A and HNF4A cause
      a progressive pancreatic beta-cell dysfunction and hyperglycemia that can result
      in microvascular complications. Sulfonylureas are effective in these patients by
      acting on adenosine triphosphate (ATP)-sensitive potassium channels, although
      insulin therapy may be required later in life. Mutations in the HNF1B (MODY 5) is
      associated with pancreatic agenesis, renal abnormalities, genital tract
      malformations, and liver dysfunction. Compared to MODY 1, 2, 3, and 5, the
      remaining subtypes of MODY have a much lower prevalence. In this review, we
      summarize the main clinical and laboratory characteristics of the common and
      rarer causes of MODY. 

PMID- 25581749
TI  - Cushing syndrome related to leukemic infiltration of the central nervous system.
AB  - BACKGROUND: Cushing syndrome (CS) due to central nervous system (CNS)
      infiltration of hematological malignancy is a rare finding. CASE: A 6.5-year-old
      boy with B cell acute lymphoblastic leukemia (ALL) came with excessive weight
      gain, headache, and irritability over last 2 months. CNS was not involved at
      diagnosis of ALL. On examination, the child had central obesity, moon facies, and
      buffalo hump. His height was at 3rd-25th percentile, weight was at >97th
      percentile, and blood pressure was >99th percentile. Serum cortisol was high in
      morning (25 MUg/dL), at 12 a.m. (19.3 MUg/dL) and remained elevated (7.5 MUg/dL)
      after overnight dexamethasone test. Examination of cerebrospinal fluid (CSF)
      revealed blast cells suggestive of CNS relapse. Our second case was a 2.5-year
      old girl with precursor B cell ALL, came with complaints of excessive weight
      gain, and increased appetite over last 3 months. On examination, the child had
      Cushingoid facies with trunkal obesity. Blood pressure was normal. Serum cortisol
      at 8 a.m. (40.4 MUg/dL), midnight (13.8 MUg/dL), and after dexamethasone
      suppression test (22 MUg/dL) was high. CSF examination showed blast cells. We
      diagnosed both cases with adrenocorticotropic hormone-dependent CS due to CNS
      relapse based on the above findings. CONCLUSION: We have reported two cases of CS
      due to CNS relapse of ALL. CS is a very rare manifestation of CNS relapse in
      patients with leukemia, and the exact pathogenesis is not clear.

PMID- 25581750
TI  - Schwann cell transplantation for spinal cord injury repair: its significant
      therapeutic potential and prospectus.
AB  - Transplantation of Schwann cells (SCs) is a promising therapeutic strategy for
      spinal cord repair. The introduction of SCs into the injured spinal cord has been
      shown to reduce tissue loss, promote axonal regeneration, and facilitate
      myelination of axons for improved sensorimotor function. The pathology of spinal
      cord injury (SCI) comprises multiple processes characterized by extensive cell
      death, development of a milieu inhibitory to growth, and glial scar formation,
      which together limits axonal regeneration. Many studies have suggested that
      significant functional recovery following SCI will not be possible with a single
      therapeutic strategy. The use of additional approaches with SC transplantation
      may be needed for successful axonal regeneration and sufficient functional
      recovery after SCI. An example of such a combination strategy with SC
      transplantation has been the complementary administration of neuroprotective
      agents/growth factors, which improves the effect of SCs after SCI. Suspension of
      SCs in bioactive matrices can also enhance transplanted SC survival and increase
      their capacity for supporting axonal regeneration in the injured spinal cord.
      Inhibition of glial scar formation produces a more permissive interface between
      the SC transplant and host spinal cord for axonal growth. Co-transplantation of
      SCs and other types of cells such as olfactory ensheathing cells, bone marrow
      mesenchymal stromal cells, and neural stem cells can be a more effective therapy
      than transplantation of SCs alone following SCI. This article reviews some of the
      evidence supporting the combination of SC transplantation with additional
      strategies for SCI repair and presents a prospectus for achieving better outcomes
      for persons with SCI. 

PMID- 25581751
TI  - The effect of nicotine and cotinine on human gingival fibroblasts attachment to
      root surfaces.
AB  - BACKGROUND: Different compounds of smoking (e.g., nicotine and cotinine) are risk
      factors for various diseases such as oral cancer and periodontal diseases. Some
      studies reported the negative effects of nicotine on cell proliferation and
      differentiation. The present in vitro study assessed the effects of nicotine and
      cotinine (long-acting metabolite of nicotine) on the attachment and viability of
      human gingival fibroblast (HGF) cells to tooth root surfaces. METHODS: A total of
      70 teeth specimens were placed into 48-well culture plates and covered with HGF
      cell suspension, in complete Dulbecco's modified Eagle's medium culture medium
      containing 1 nM, 1 MUm, 1 mM, and 5 mM of nicotine and cotinine concentrations.
      Cellular attachment and viability measured using an MTT assay and a scanning
      electron microscope were used for cell morphological evaluation. RESULTS: After
      24 h, low (nanomolar and micromolar) and high concentrations (millimolar) of
      nicotine and cotinine caused a significant reduction in the initial cell adhesion
      in comparison with the control group, but no significant difference was observed
      between the nicotine and the cotinine groups (p<0.05). Dentally attached cells
      with low concentrations of nicotine and cotinine proliferated 48 h after
      exposure, the same as the control group. However, dentally attached cells with
      high concentrations of nicotine and cotinine (especially 5 mM) did not
      proliferate 24 h after exposure (p<0.05). CONCLUSIONS: Low concentrations of
      nicotine and cotinine caused a reduction in the initial cell adhesion. However,
      no significant adverse effects on the proliferation of attached cells were seen
      in the longer period. High concentrations of nicotine and cotinine have adverse
      effects on the cell adhesion and proliferation of HGF cells.

PMID- 25581752
TI  - Aspartate 496 from the subsite S2 drives specificity of human dipeptidyl
      peptidase III.
AB  - Human dipeptidyl peptidase III (hDPP III) is a member of the M49 metallopeptidase
      family, which is involved in intracellular protein catabolism and oxidative
      stress response. To investigate the structural basis of hDPP III preference for
      diarginyl arylamide, using site-directed mutagenesis, we altered its S2 subsite
      to mimic the counterpart in yeast enzyme. Kinetic studies revealed that the
      single mutant D496G lost selectivity due to the increase of the Km value. The
      D496G, but not S504G, showed significantly decreased binding of peptides with N
      terminal arginine, and of tynorphin. The results obtained identify Asp496 as an
      important determinant of human DPP III substrate specificity. 

PMID- 25581753
TI  - Sortase-mediated backbone cyclization of proteins and peptides.
AB  - Backbone cyclization has a profound impact on the biological activity and thermal
      and proteolytic stability of proteins and peptides. Chemical methods for
      cyclization are not always feasible, especially for large peptides or proteins.
      Recombinant Staphylococcus aureus sortase A shows potential as a new tool for the
      cyclization of both proteins and peptides. In this review, the scope and
      background of the sortase-mediated cyclization are discussed. High efficiency,
      versatility, and easy access make sortase A a promising cyclization tool, both
      for recombinant and chemo-enzymatic production methods. 

PMID- 25581754
TI  - Enzymatic control of cysteinyl thiol switches in proteins.
AB  - The spatiotemporal modification of specific cysteinyl residues in proteins has
      emerged as a novel concept in signal transduction. Such modifications alter the
      redox state of the cysteinyl thiol group, with implications for the structure and
      biological function of the protein. Regulatory cysteines are therefore classified
      as 'thiol switches'. In this review we emphasize the relevance of enzymes for
      specific and efficient redox sensing, evaluate prerequisites and general
      properties of redox switches, and highlight mechanistic principles for toggling
      thiol switches. Moreover, we provide an overview of potential mechanisms for the
      initial formation of regulatory disulfide bonds. In brief, we address the three
      basic questions (i) what defines a thiol switch, (ii) which parameters confer
      signal specificity, and (iii) how are thiol switches oxidized? 

PMID- 25581755
TI  - Tackling the biophysical properties of sphingolipids to decipher their biological
      roles.
AB  - From the most simple sphingoid bases to their complex glycosylated derivatives,
      several sphingolipid species were shown to have a role in fundamental cellular
      events and/or disease. Increasing evidence places lipid-lipid interactions and
      membrane structural alterations as central mechanisms underlying the action of
      these lipids. Understanding how these molecules exert their biological roles by
      studying their impact in the physical properties and organization of membranes is
      currently one of the main challenges in sphingolipid research. Herein, we review
      the progress in the state-of-the-art on the biophysical properties of
      sphingolipid-containing membranes, focusing on sphingosine, ceramides, and
      glycosphingolipids. 

PMID- 25581756
TI  - Cytosolic thiol switches regulating basic cellular functions: GAPDH as an
      information hub?
AB  - Cytosolic glyceraldehyde 3-phosphate dehydrogenase (GAPDH, E.C. 1.2.1.12) is
      present in all organisms and catalyzes the oxidation of triose phosphate during
      glycolysis. GAPDH is one of the most prominent cellular targets of oxidative
      modifications when reactive oxygen and nitrogen species are formed during
      metabolism and under stress conditions. GAPDH harbors a strictly conserved
      catalytic cysteine, which is susceptible to a variety of thiol modifications,
      including S-sulfenylation, S-glutathionylation, S-nitrosylation, and S
      sulfhydration. Upon reversible oxidative thiol modification of GAPDH, glycolysis
      is inhibited leading to a diversion of metabolic flux through the pentose
      phosphate cycle to increase NADPH production. Furthermore, oxidized GAPDH may
      adopt new functions in different cellular compartments including the nucleus, as
      well as in new microcompartments associated with the cytoskeleton, mitochondria
      and plasma membrane. This review focuses on the recently discovered mechanism
      underlying the eminent reactivity between GAPDH and hydrogen peroxide and the
      subsequent redox-dependent moonlighting functions discriminating between the
      induction either of adaptive responses and adjustment of metabolism or of cell
      death in yeast, plants, and mammals. In light of the summarized results,
      cytosolic GAPDH might function as a sensor for redox signals and an information
      hub to transduce these signals for appropriate responses. 

PMID- 25581757
TI  - Recent advances in biomarkers for Parkinson's disease focusing on biochemicals,
      omics and neuroimaging.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative disorders,
      involving progressive loss of the nigro-striatal dopaminergic neurons. Cardinal
      symptoms including tremors, muscle rigidity, drooping posture, drooping, walking
      difficulty, and autonomic symptoms appear when a significant number of
      nigrostriatal dopaminergic neurons have already been destroyed. Hence, reliable
      biomarkers are needed for early and accurate diagnosis to measure disease
      progression and response to therapy. We review the current status of protein and
      small molecule biomarkers involved in oxidative stress, protein aggregation and
      inflammation etc. which are present in cerebrospinal fluid, human blood, urine or
      saliva. In recent years, advances in genomics, proteomics, metabolomics, and
      functional brain imaging techniques have led to new insights into the
      pathoetiology of PD. Further studies in the novel discovery of PD biomarkers will
      provide avenues to treat PD patients more effectively with few or no side
      effects. 

PMID- 25581758
TI  - Application of real-time PCR of sex-independent insertion-deletion polymorphisms
      to determine fetal sex using cell-free fetal DNA from maternal plasma.
AB  - BACKGROUND: Prenatal diagnosis of sex-linked disorders requires invasive
      procedures, carrying a risk of miscarriage of up to 1%. Cell-free fetal DNA
      (cffDNA) present in cell-free DNA (cfDNA) from maternal plasma offers a non
      invasive source of fetal genetic material for analysis. Detection of Y-chromosome
      sequences in cfDNA indicates presence of a male fetus; in the absence of a Y
      chromosome signal a female fetus is inferred. We aimed to validate the clinical
      utility of insertion-deletion polymorphisms (INDELs) to confirm presence of a
      female fetus using cffDNA. METHODS: Quantitative real-time PCR (qPCR) for the Y
      chromosome-specific sequence, SRY, was performed on cfDNA from 82 samples at 6-39
      gestational weeks. In samples without detectable SRY, qPCRs for eight INDELs were
      performed on maternal genomic DNA and cfDNA. Detection of paternally inherited
      fetal alleles in cfDNA negative for SRY confirmed a female fetus. RESULTS: Fetal
      sex was correctly determined in 77/82 (93.9%) cfDNA samples. SRY was detected in
      all 39 samples from male-bearing pregnancies, and none of the 43 female-bearing
      pregnancies (sensitivity and specificity of SRY qPCR is therefore 100%; 95% CI
      91%-100%). Paternally inherited fetal alleles were detected in 38/43 samples with
      no SRY signal, confirming the presence of a female fetus (INDEL assay sensitivity
      is therefore 88.4%; 95% CI 74.1%-95.6%). Since paternally inherited fetal INDELs
      were not used in women bearing male fetuses, the specificity of INDELs cannot be
      calculated. Five cfDNA samples were negative for both SRY and INDELS.
      CONCLUSIONS: We have validated a non-invasive prenatal test to confirm fetal sex
      as early as 6 gestational weeks using cffDNA from maternal plasma.

PMID- 25581759
TI  - Performance characteristics of a new automated method for measurement of anti
      cyclic citrullinated peptide.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune
      disease affecting approximately 1%-2% of the population worldwide. RA is a
      potentially crippling disease since it results in malformation of the joints. RA
      is mostly diagnosed based on clinical manifestations but serological tests
      against autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated
      peptides (aCCP), are available. The presence of aCCP antibodies is strongly
      associated with a more severe, destructive disease course. Recently, a new test
      for the measurement of aCCP antibodies on the IMMULITE 2000(XPi) platform was
      developed by Siemens Healthcare. In this study we investigated the performance
      characteristics of this new aCCP test in four different hospital laboratories and
      compared the new test with three different commercially available platforms.
      METHODS: Samples were collected from patients presented to the hospital for aCCP
      measurement. Serum aCCP levels were determined by aCCP (Ig)G assay for IMMULITE
      2000(XPi) systems (Siemens Healthcare), ImmunoScan RA enzyme-linked immunosorbent
      assay (ELISA) test (Eurodiagnostica), Immunocap 250 (Thermofisher) or aCCP IgG
      assay on the Modular system (Roche Diagnostics). The evaluation protocol
      consisted of within-run imprecision (20 sequential runs), between-run imprecision
      (16 workdays), comparison of serum and plasma measurement and method comparison.
      RESULTS: The within-run imprecision (n=20) for aCCP IgG assay on three different
      IMMULITE 2000(XPi) systems ranged from 3.0% to 6.9% at levels 3.2-171.2 U/mL.
      Between-run imprecision (n=16 days) ranged from 5.2% to 11% at levels of 3.2
      106.9 U/mL. Method comparison showed good correlation when samples were measured
      on two different Immulite analyzers in two different hospital laboratories
      [0.21+0.96x (n=40)]. Method comparison of the IMMULITE 2000(XPi) aCCP test with
      aCCP on Immunoscan RA ELISA (n=112), Immunocap 250 (n=105) and the Modular system
      (n=289) resulted in a concordance of 90.2%, 93.3% and 94.8%, respectively.
      Correlation of serum versus heparin samples showed a correlation of 0.12+1.08x
      for the Immulite 2000(XPi) test. CONCLUSIONS: The aCCP assay on the IMMULITE
      2000(XPi) has good performance characteristics and shows high level of
      concordance with the aCCP test on Immunoscan RA ELISA test, Immunocap 250 and the
      Modular systems.

PMID- 25581760
TI  - A high selectivity and sensitivity analytical method for the analysis of 8
      hydroxy-2'-deoxyguanosine in the urine of Alzheimer's disease patients.

PMID- 25581761
TI  - Emerging biomarkers in the detection and prognosis of prostate cancer.
AB  - The prostate-specific antigen (PSA) is currently the most used tumor marker in
      the early detection of the prostate cancer (PCa), despite its low specificity and
      low negative predictive value. New biomarkers, including urine prostate cancer
      gene 3 (PCA3) score, Prostate Health Index (PHI), and the four-kallikrein panel,
      have been investigated during recent years especially with the aim of detecting
      aggressive PCa. Results suggest the ability of these biomarkers to improve the
      specificity of PSA in the detection of PCa, although there are not enough results
      directly comparing these biomarkers to know their complementarity. The
      relationship with PCa aggressiveness seems to be confirmed for PHI and for the
      four-kallikrein panel, but not for PCA3 score. However, available results suggest
      that emerging biomarkers may be useful as part of a multivariable approach for
      the screening and prognosis of PCa. Nevertheless, larger prospective studies
      comparing these biomarkers are necessary to evaluate definitely their value in
      the management of early PCa. 

PMID- 25581762
TI  - Economic evaluation of procalcitonin-guided antibiotic therapy in acute
      respiratory infections: a US health system perspective.
AB  - BACKGROUND: Whether or not antibiotic stewardship protocols based on
      procalcitonin levels results in cost savings remains unclear. Herein, our
      objective was to assess the economic impact of adopting procalcitonin testing
      among patients with suspected acute respiratory tract infection (ARI) from the
      perspective of a typical US integrated delivery network (IDN) with a 1,000,000
      member catchment area or enrollment. METHODS: To conduct an economic evaluation
      of procalcitonin testing versus usual care we built a cost-impact model based on
      patient-level meta-analysis data of randomized trials. The meta-analytic data was
      adapted to the US setting by applying the meta-analytic results to US lengths of
      stay, costs, and practice patterns. We estimated the annual ARI visit rate for
      the one million member cohort, by setting (inpatient, ICU, outpatient) and ARI
      diagnosis. RESULTS: In the inpatient setting, the costs of procalcitonin-guided
      compared to usual care for the one million member cohort was $2,083,545, compared
      to $2,780,322, resulting in net savings of nearly $700,000 to the IDN for 2014.
      In the ICU and outpatient settings, savings were $73,326 and $5,329,824,
      respectively, summing up to overall net savings of $6,099,927 for the cohort.
      RESULTS were robust for all ARI diagnoses. For the whole US insured population,
      procalcitonin-guided care would result in $1.6 billion in savings annually.
      CONCLUSIONS: Our results show substantial savings associated with procalcitonin
      protocols of ARI across common US treatment settings mainly by direct reduction
      in unnecessary antibiotic utilization. These results are robust to changes in key
      parameters, and the savings can be achieved without any negative impact on
      treatment outcomes.

PMID- 25581763
TI  - Elevated circulating levels of lipoprotein-associated phospholipase A2 in obese
      children.
AB  - BACKGROUND: Obesity and cardiovascular disease (CVD) often co-exist, but the
      pathophysiologic mechanisms that link the two are not fully understood.
      Lipoprotein-associated phospholipase A2 (Lp-PLA2) is involved in the modification
      of lipids within atheromatous plaques. Recently, circulating Lp-PLA2 was found to
      be predictive of thromboembolic episodes in adults, independently of a variety of
      other potential risk factors, including markers of inflammation, renal function,
      and hemodynamic stress. However, the function of this lipase and its importance
      as a biomarker in childhood obesity is much less studied. The aim of the study
      was to study Lp-PLA2, a non-traditional risk factor of CVD, in obese children.
      METHODS: Sixty-seven lean [39 boys and 28 girls, mean body mass index (BMI) z
      score -0.2+/-0.8] and 66 obese (32 boys and 34 girls, mean BMI z-score 4.4+/-1.2)
      age-matched (p=0.251) children, aged 6-12 years, were studied. BMI z-score was
      calculated based on the Greek BMI growth curves, and children were categorized as
      obese according to the Cole criteria. All children underwent physical examination
      and a fasting morning blood sample was obtained for glucose, insulin, lipid
      profile, and Lp-PLA2 assessment. Plasma concentrations of Lp-PLA2 were determined
      by a commercially available Lp-PLA2 enzyme-linked immunosorbent assay kit (PLAC
      Test), while other measurements were performed using standard methods. RESULTS:
      Plasma Lp-PLA2 levels were significantly higher in obese children (322.5+/-77.8
      ng/mL) compared with normal-weight ones (278.0+/-64.4 ng/mL, p<0.001). Lp-PLA2
      concentrations were significantly correlated with the BMI z-score (p=0.004).
      Receiver operating characteristic analysis on Lp-PLA2 values resulted in
      significant areas under the curve (AUC) for distinguishing between obese and
      normal-weight groups of children (AUC, 0.726; p<0.001). CONCLUSIONS: We found
      significantly higher Lp-PLA2 levels in obese children than lean controls.
      Interestingly, they all had levels >200 ng/mL, which are considered to correlate
      with atherosclerosis and a high thromboembolic risk in adults. The positive
      correlation of Lp-PLA2 with BMI suggests that Lp-PLA2 might be the link between
      obesity and increased cardiovascular risk, which can be elevated even at a very
      young age. Measurement of Lp-PLA2 in plasma could therefore represent a further
      biomarker for assessing increased CVD risk in obese children and adolescents.

PMID- 25581764
TI  - Rapid diagnosis of cryptococcal meningitis by Turk staining.

PMID- 25581765
TI  - The effects of short-term high-intensity interval training vs. moderate-intensity
      continuous training on plasma levels of nesfatin-1 and inflammatory markers.
AB  - OBJECTIVES: Exercise training is an effective method of weight management, and
      knowing about its influence on the hormones involved in the regulation of food
      intake and inflammation could be useful for body weight management. Therefore,
      the purpose of this study was to compare the effects of 6 weeks of high-intensity
      interval training (HIIT) and moderate-intensity continuous exercise training
      (MCT) on nesfatin-1, interleukin (IL)-6, and tumor necrosis factor alpha (TNF
      alpha). DESIGN AND METHODS: Thirty sedentary overweight men (Mean+/-SD; age, 25+/
      1 years) were divided into three (n=10) body mass index-matched groups. The
      participants in the training groups performed either HIIT or MCT protocols 3 days
      per week for 6 weeks followed by a week of detraining. RESULTS: Plasma IL-6 and
      TNF-alpha did not significantly change after training, but nesfatin increased
      significantly only with HIIT compared with the control group (p<0.05). In
      addition, fasting glucose, insulin, and homeostasis model estimated insulin
      resistance (HOMA-IR), decreased significantly following both HIIT and MCT
      training (p<0.05). After a detraining period, the plasma nesfatin-1 did not
      return to pre-training levels in the HIIT group. CONCLUSIONS: Both the HIIT and
      MCT groups had similar effects on inflammatory markers and insulin resistance in
      men who are overweight, but the HIIT seems to have better anorectic effects (as
      indicated by nesfatin) compared with MCT.

PMID- 25581766
TI  - Multilocus methylation defects in imprinting disorders.
AB  - Mammals inherit two complete sets of chromosomes, one from the father and one
      from the mother, and most autosomal genes are expressed from both maternal and
      paternal alleles. In imprinted genes, the expression of the allele is dependent
      upon its parental origin. Appropriate regulation of imprinted genes is important
      for normal development, with several genetic diseases associated with imprinting
      defects. A common process for controlling gene activity is methylation. The first
      steps for understanding the functions of DNA methylation and its regulation in
      mammalian development have led us to identify common (epi)genetic mechanisms
      involved in the eight human congenital imprinting disorders.

PMID- 25581767
TI  - Testing genotypes-phenotype relationships using permutation tests on association
      rules.
AB  - Association rule mining is a knowledge discovery technique which informs
      researchers about relationships between variables in data. These relationships
      can be focused to a specific set of response variables. We propose an augmented
      version of this method to discover groups of genotypes which relate to specific
      outcomes. We derive the methodology to find these candidate groups of genotypes
      and illustrate how the method works on data regarding neuroinvasive complications
      of West Nile virus and through simulation.

PMID- 25581768
TI  - Complementary and alternative medicine in diabetes (CALMIND)--a prospective
      study.
AB  - BACKGROUND: This study aims to further elucidate the demographic and diabetes
      characteristics of diabetic patients in Australia who use complementary and
      alternative medicines (CAM). METHODS: This was a prospective, cross-sectional
      questionnaire-based study of 149 patients with diabetes attending a general
      endocrine clinic in a tertiary referral hospital in Sydney, Australia. RESULTS:
      Thirty-seven patients (25%) stated they had used CAM therapies within the past 5
      years. Vitamins (53%) were the most common CAM therapy used. A greater number of
      CAM nonusers reported calf pain whilst walking (21% vs. 9%, p=0.051), and HbA1c
      values were lower for CAM nonusers (7.7% vs. 8.1%, p=0.057). Amongst CAM users, a
      majority of patients (85%) did not consult with their specialist or general
      practitioner prior to starting CAM therapy. CONCLUSIONS: With the increasing
      burden of diabetes, health practitioners will need to be more vigilant and
      understanding of the potential impact of CAM use on diabetes management.

PMID- 25581769
TI  - Bishop Paul of Merida, and the first known caesarean section on a living woman.

PMID- 25581771
TI  - Do Cochrane systematic reviews meet WHO needs?

PMID- 25581770
TI  - Association of socioeconomic status with treatment delays, disease activity,
      joint damage, and disability in rheumatoid arthritis.
AB  - OBJECTIVE: To examine the association of socioeconomic status (SES) and delays in
      disease-modifying antirheumatic drug (DMARD) treatment with clinical measures in
      rheumatoid arthritis (RA) patients. METHODS: RA patients were recruited from
      rheumatology practices. We assessed SES based on education, occupation, and
      income, and divided patients into tertiles. The time from RA symptom onset to
      DMARD initiation (DMARD lag) was determined by self-report of the 2 dates, and
      distance to the rheumatologist (Distance) was obtained from Google Maps. We
      examined disease activity, determined by the Disease Activity Score in 28 joints
      using the erythrocyte sedimentation rate (DAS28-ESR); joint damage, determined
      from hand radiographs by Sharp scores; and physical disability, determined by the
      modified Health Assessment Questionnaire (M-HAQ). We used linear regression
      models to examine the relationship between clinical measures and SES, Distance,
      and DMARD lag. RESULTS: We recruited 1,209 RA patients, 1,159 of whom had
      received DMARD treatment. Mean +/- SD DMARD lag was 6.9 +/- 9.0 years. On
      average, patients with lower SES waited 8.5 +/- 10.2 years after onset of RA
      symptoms to begin DMARD treatment, compared to those in the middle and upper SES
      tertiles who waited 6.1 +/- 7.9 years (P = 0.002) and 6.1 +/- 8.6 years (P =
      0.009), respectively. Each year of delayed treatment was associated with a DAS28
      ESR increase of 0.02 (P <= 0.001), a Sharp score increase of 1.33 (P <= 0.001),
      and an M-HAQ score increase of 0.01 (P <= 0.001). CONCLUSION: Low SES was
      associated with delay in DMARD initiation, and both were independently associated
      with worse clinical measures in RA. Strategies to reduce treatment delay in low
      SES RA patients are needed.

PMID- 25581773
TI  - Latino and Latina Adolescents' Help-seeking Behaviors and Attitudes Regarding
      Suicide Compared to Peers with Recent Suicidal Ideation.
AB  - Although Latinas have consistently reported higher rates of suicidal behavior for
      the past 20 years (CDC, 1996), there is a dearth of information regarding their
      help-seeking attitudes and behaviors when dealing with distress and suicide.
      Associations between adolescents' ideation and help-seeking from adults were
      different for non-Hispanic Whites and Latinos from 14 high schools (N = 4,983).
      Among females, ideators and Latinas reported lower levels of help-seeking
      attitudes than nonideators and non-Hispanic Whites. Males showed interaction
      effects of ideation by race/ethnicity on help-seeking. Within sex by
      race/ethnicity, differences showed that while non-Hispanic White students
      reported consistent differences between suicidal ideation and no reported
      suicidal ideation, Latinos were more similar between these groups, particularly
      with having support from friends and family to seek help from adults. Research
      should clarify how culture contributes to decreased help-seeking norms among
      those with suicidal ideation.

PMID- 25581772
TI  - Adaptive endoplasmic reticulum stress alters cellular responses to the
      extracellular milieu.
AB  - The ability to respond to perturbations in endoplasmic reticulum (ER) function is
      a critical property for all cells. In the presence of chronic ER stress, the cell
      must adapt so that cell survival is favored or the stress may promote apoptosis.
      In some pathological processes, such as neurodengeneration, persistent ER stress
      can be tolerated for an extended period, but eventually cell death occurs. It is
      not known how an adaptive response converts from survival into apoptosis. To gain
      a better understanding of the role of adaptive ER stress in neurodegeneration, in
      this study, with a neuronal cell line SH-SY5Y and primary motor neuron-glia cell
      mixed cultures, we induced adaptive ER stress and modified the extracellular
      environment with physiologically relevant changes that alone did not activate ER
      stress. Our data demonstrate that an adaptive ER stress favored neuronal cell
      survival, but when cells were exposed to additional physiological insults the
      level of ER stress was increased, followed by activation of the caspase pathway.
      Our results indicate that an adaptive ER stress response could be converted to
      apoptosis when the external cellular milieu changed, suggesting that the
      conversion from prosurvival to proapoptotic pathways can be driven by the
      external milieu. This conversion was due at least partially to an increased level
      of ER stress.

PMID- 25581774
TI  - Cerebral toxoplasmosis in an adolescent post allogeneic hematopoietic stem cell
      transplantation: successful outcome by antiprotozoal chemotherapy and CD4+ T
      lymphocyte recovery.
AB  - Toxoplasmosis is a rare opportunistic infection in pediatric allogeneic
      hematopoietic stem cell transplant (allo-HSCT) recipients and associated with
      severe T-cell deficiency. Here, we report the successful management of cerebral
      toxoplasmosis in a 15-year-old adolescent 4 months post allo-HSCT for non-Hodgkin
      lymphoma through rapid invasive diagnostics, long-term antiprotozoal
      chemotherapy, and an hematopoietic stem cell boost for persistently poor graft
      function. While supportive care and antiprotozoal chemotherapy achieved
      stabilization, definite improvement only occurred following recovery of CD4(+) T
      lymphocytes to >100 cells/MUL. At 5 years after the diagnosis of toxoplasmosis,
      the patient is in continuing remission with normalized clinical and imaging
      findings. 

PMID- 25581775
TI  - Modular synthesis of linear bis- and tris-monodentate fused [6]polynorbornane
      based ligands and their assembly into coordination cages.
AB  - A modular approach has been developed for the synthesis of rigid linear di- and
      tritopic ligands based on a fused [6]polynorbornane scaffold. The design provides
      up to three sites for installing functionality, including both "ends" and a
      "central" position with the advantage that each region can be independently
      addressed during synthesis. To illustrate the utility of the approach, both
      pyridyl and picolyl units were incorporated to provide six new ligands, with
      centers and ends either matched or mismatched. Indeed, both [M2L4] cages with
      endohedral functionality and [M3L4] complexes were cleanly produced from these
      ligands with assembled structures confirmed by using (1)H NMR spectroscopy, HRMS,
      and molecular modelling.

PMID- 25581776
TI  - Crystal and molecular structure of the analgesic tetrapeptide, L-Phe-L-Leu-L-Pro
      L-Ser.
AB  - The tetrapeptide, L-Phe-L-Leu-L-Pro-L-Ser (FLPS), alleviates pain in a rat model
      of post-surgery pain. The crystal structure of the tetrapeptide is solved at high
      resolution (0.54 A). The asymmetric unit contains two FLPS molecules, one Zn ion,
      and four molecules of water with a formula of [Zn(C23H33N4O6)2(H2O)4]. Each Zn
      ion is octahedrally coordinated with Phe and Ser residues from four peptide
      molecules [2N+4O]. The linking of Phe and Ser residues of one FLPS molecule to
      three other FLPS molecules by Zn ion forms a complex consisting of chains of
      metal ions and FLPS molecules oriented along the b axis. Analysis of molecular
      packing reveals the coexistence of two FLPS conformers in the same crystal. The
      crystallographic parameters for [Zn(C23H33N4O6)2(H2O)4] are as follows: space
      group P21 21 21 , a = 9.8698(2) A, alpha = 90 degrees , b = 20.1844(4) A, beta =
      90 degrees , c = 25.9302(6) A, gamma = 90 degrees . Volume = 5165.71(19) A(3), Z
      = 4, density (calc) = 1.364 Mg/cm(3), and agreement factor R1 = 4.13%.

PMID- 25581777
TI  - Full solar spectrum light driven thermocatalysis with extremely high efficiency
      on nanostructured Ce ion substituted OMS-2 catalyst for VOCs purification.
AB  - The nanostructured Ce ion substituted cryptomelane-type octahedral molecular
      sieve (OMS-2) catalyst exhibits strong absorption in the entire solar spectrum
      region. The Ce ion substituted OMS-2 catalyst can efficiently transform the
      absorbed solar energy to thermal energy, resulting in a considerable increase of
      temperature. By combining the efficient photothermal conversion and
      thermocatalytic activity of the Ce ion substituted OMS-2 catalyst, we carried out
      full solar spectrum, visible-infrared, and infrared light driven catalysis with
      extremely high efficiency. Under the irradiation of full solar spectrum, visible
      infrared, and infrared light, the Ce ion substituted OMS-2 catalyst exhibits
      extremely high catalytic activity and excellent durability for the oxidation of
      volatile organic pollutants such as benzene, toluene, and acetone. Based on the
      experimental evidence, we propose a novel mechanism of solar light driven
      thermocatalysis for the Ce ion substituted OMS-2 catalyst. The reason why the Ce
      ion substituted OMS-2 catalyst exhibits much higher catalytic activity than pure
      OMS-2 and CeO2/OMS-2 nano composite under the full solar spectrum irradiation is
      discussed. 

PMID- 25581778
TI  - Insulin therapy and fetoplacental vascular function in gestational diabetes
      mellitus.
AB  - NEW FINDINGS: What is the topic of this review? This review focuses on the
      effects of insulin therapy on fetoplacental vasculature in gestational diabetes
      mellitus and the potentiating effects of adenosine on this therapy. What advances
      does it highlight? This review highlights recent studies exploring a potential
      functional link between insulin receptors and their dependence on adenosine
      receptor activation (insulin-adenosine axis) to restore placental endothelial
      function in gestational diabetes mellitus. Gestational diabetes mellitus (GDM) is
      a disease that occurs during pregnancy and is associated with maternal and fetal
      hyperglycaemia. Women with GDM are treated via diet to control their glycaemia;
      however, a proportion of these patients do not achieve the recommended values of
      glycaemia and are subjected to insulin therapy until delivery. Even if a diet
      treated GDM pregnancy leads to normal maternal and newborn glucose levels,
      fetoplacental vascular dysfunction remains evident. Thus, control of glycaemia
      via diet does not prevent GDM-associated fetoplacental vascular and metabolic
      alterations. We review the available information regarding insulin therapy in the
      context of its potential consequences for fetoplacental vascular function in GDM.
      We propose the possibility that insulin therapy to produce normoglycaemia in the
      mother and newborn may require additional therapeutic measures to restore the
      normal metabolic condition of the vascular network in GDM. A role for A1 and A2A
      adenosine receptors and insulin receptors A and B as well as a potential
      functional link in the cell signalling associated with the activation of these
      receptors is proposed. This possibility could be helpful for the planning of
      strategies, including adenosine receptor-improved insulin therapy, for the
      treatment of GDM patients, thereby promoting the wellbeing of the growing fetus,
      newborn and mother.

PMID- 25581779
TI  - Smoking-induced skeletal muscle dysfunction: from evidence to mechanisms.
AB  - Smoking is the most important risk factor for the development of chronic
      obstructive pulmonary disease (COPD). Patients with COPD commonly suffer from
      skeletal muscle dysfunction, and it has been suggested that cigarette smoke
      exposure contributes to the development of skeletal muscle dysfunction even
      before overt pulmonary pathology. This review summarizes the evidence that
      muscles of nonsymptomatic smokers are weaker and less fatigue resistant than
      those of nonsmokers. Although physical inactivity of many smokers contributes to
      some alterations observed in skeletal muscle, exposure to cigarette smoke per se
      can also induce skeletal muscle dysfunction. Cigarette smoke constituents and
      systemic inflammatory mediators enhance proteolysis and inhibit protein
      synthesis, leading to loss of muscle mass. Reduced skeletal muscle contractile
      endurance in smokers may result from impaired oxygen delivery to the mitochondria
      and ability of the mitochondria to generate ATP due to interaction of carbon
      monoxide with hemoglobin, myoglobin, and components of the respiratory chain.
      Besides hampering contractile function, smoking may have immediate beneficial
      effects on motor skills, which are attributable to nicotine. In contrast to
      pulmonary pathology, many of the effects of smoking on skeletal muscle are most
      likely reversible by smoking cessation. 

PMID- 25581780
TI  - N-(2,4)-dinitrophenyl-L-arginine Interacts with EphB4 and Functions as an EphB4
      Kinase Modulator.
AB  - The erythropoietin-producing hepatocellular carcinoma receptor B4 is a receptor
      tyrosine kinase whose expression is preserved in various malignancies, including
      colon, gastric, and breast carcinoma. Hepatocellular carcinoma receptor B4
      presence in tumor cells and involvement in cancer suppression makes it a
      potential therapeutic target for activating compounds. Moreover, modulators of
      its activity also have a strong potential to be used in diagnosis and therapy
      monitoring. We used virtual ligand screening to identify novel hepatocellular
      carcinoma receptor B4 kinase modulators for experimental testing. Three
      independent assay platforms confirmed that dinitrophenyl-L-arginine is likely to
      affect the kinase activity of hepatocellular carcinoma receptor B4. An enzyme
      coupled spectrophotometric assay has been used to examine this possibility and
      may prove to be useful for assessing other novel kinase modulator candidates.
      Overall, our observations suggest that dinitrophenyl-L-arginine has an activating
      effect on hepatocellular carcinoma receptor B4 and, therefore, more efficient
      derivatives may have therapeutic effects in tumors where hepatocellular carcinoma
      receptor B4 exhibits antimalignant properties. The hepatocellular carcinoma
      receptor B4-activating effect is discussed with respect to previously described
      mechanisms, using predicted and experimental structures for docked ligands. As a
      novel kinase activity modulator, dinitrophenyl-L-arginine may provide new
      insights into molecular mechanisms by which kinases are activated or regulated,
      and may serve as a lead compound for the generation of novel hepatocellular
      carcinoma receptor B4-activating therapeutic compounds. 

PMID- 25581781
TI  - Diagnostic value of core needle biopsy and fine-needle aspiration in salivary
      gland lesions.
AB  - BACKGROUND: Core needle biopsy (CNB) has gained acceptance as a minimally
      invasive procedure in the head and neck. Nevertheless, many concerns arise
      regarding the value and safety of this method in the assessment of salivary gland
      lesions. METHODS: This prospective study comprises 111 patients with a salivary
      gland lesion. The results of ultrasound-guided CNB were compared with those of
      fine-needle aspiration (FNA) in the 103 histologically verified cases. RESULTS:
      CNB achieved a higher accuracy than FNA in identifying true neoplasms (98% vs
      91%) and detecting malignancy (99% vs 87%), and was also superior to FNA
      providing a specific diagnosis (93% vs 74%). In both methods, no complications,
      such as bleeding, infection, nerve injury, or tumor-cell seeding, occurred.
      CONCLUSION: CNB is a simple, safe, and highly accurate procedure, which should be
      considered as an additional diagnostic tool in the assessment of salivary gland
      lesions. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E346-E352, 2016.

PMID- 25581783
TI  - Intentions and trait self-control predict fruit and vegetable consumption during
      the transition to first-year university.
AB  - OBJECTIVE: To examine the independent and combined effects of Theory of Planned
      Behavior (TPB) variables and trait self-control (TSC) in the prediction of fruit
      and vegetable consumption (FVC) among first-year university students.
      PARTICIPANTS: Seventy-six first-year undergraduate university students. METHODS:
      In their first week of class (September 2011), participants completed baseline
      measures of TSC, attitudes, subjective norms, perceived behavioral control, and
      intentions about their FVC. One week later, students completed a 7-day food
      recall, from which daily FVC was calculated. RESULTS: Baseline attitudes and
      perceived behavioral control predicted intentions (adjR(2) = .58). Intentions and
      TSC predicted FVC (adjR(2) = .24). CONCLUSIONS: The TPB may be a useful framework
      on which to base a FVC intervention for first-year undergraduate students;
      however, focusing solely on increasing positive intentions to consume FVC will
      not necessarily translate into FVC behavior, as other personal- and environmental
      level variables may play a role.

PMID- 25581782
TI  - Targeting the de novo biosynthesis of thymidylate for the development of a PET
      probe for pancreatic cancer imaging.
AB  - The development of cancer-specific probes for imaging by positron emission
      tomography (PET) is gaining impetus in cancer research and clinical oncology. One
      of the hallmarks of most cancer cells is incessant DNA replication, which
      requires the continuous synthesis of nucleotides. Thymidylate synthase (TSase) is
      unique in this context because it is the only enzyme in humans that is
      responsible for the de novo biosynthesis of the DNA building block 2'-deoxy
      thymidylate (dTMP). TSase catalyzes the reductive methylation of 2'-deoxy
      uridylate (dUMP) to dTMP using (R)-N(5),N(10)-methylene-5,6,7,8-tetrahydrofolate
      (MTHF) as a cofactor. Not surprisingly, several human cancers overexpress TSase,
      which makes it a common target for chemotherapy (e.g., 5-fluorouracil). We
      envisioned that [(11)C]-MTHF might be a PET probe that could specifically label
      cancerous cells. Using stable radiotracer [(14)C]-MTHF, we had initially found
      increased uptake by breast and colon cancer cell lines. In the current study, we
      examined the uptake of this radiotracer in human pancreatic cancer cell lines
      MIAPaCa-2 and PANC-1 and found predominant radiolabeling of cancerous versus
      normal pancreatic cells. Furthermore, uptake of the radiotracer is dependent on
      the intracellular level of the folate pool, cell cycle phase, expression of
      folate receptors on the cell membrane, and cotreatment with the common
      chemotherapeutic drug methotrexate (MTX, which blocks the biosynthesis of
      endogenous MTHF). These results point toward [(11)C]-MTHF being used as PET probe
      with broad specificity and being able to control its signal through MTX co
      administration. 

PMID- 25581784
TI  - Risks for opportunistic tuberculosis infection in a cohort of 873 patients with
      inflammatory bowel disease receiving a tumor necrosis factor-alpha inhibitor.
AB  - OBJECTIVE: Real-world epidemiological data on tuberculosis (TB) infection in
      patients with inflammatory bowel disease (IBD) receiving TNF-alpha inhibitors are
      scarce. We investigated the risks for and case characteristics of TB in a large
      cohort of IBD patients treated with TNF-alpha inhibitors in Korea, where TB is
      endemic. MATERIALS AND METHODS: We performed an observational study on all TB
      cases identified in a cohort of 873 IBD subjects treated with TNF-alpha
      inhibitors from January 2001 to December 2013. The standardized incidence ratio
      (SIR) of TB was calculated using data from the matched general population.
      RESULTS: A total of 25 newly developed TB cases were identified in the cohort
      (pulmonary TB, 84% [21/25]; extrapulmonary TB, 16% [4/25]). The adjusted SIR of
      TB was 41.7 (95% confidence interval, 25.3-58.0), compared with that of the
      matched general population. Nineteen of the 25 patients (76%) developed TB within
      2-62 months of initiation of TNF-alpha inhibitor treatment despite screening
      negative for latent TB infection (LTBI), whereas three patients with LTBI (12%,
      3/25) developed TB 3 months after completion of chemoprophylaxis. The outcomes of
      TB treatment were mostly favorable, although one death from peritoneal TB was
      noted. The type of TNF-alpha inhibitor prescribed (infliximab) was a significant
      predictor of TB (p = 0.033). CONCLUSIONS: TNF-alpha inhibitor treatment
      strikingly increases the risk of TB infection in an IBD population from a TB
      endemic area. Continuous evaluation of the development of de novo TB infection in
      IBD patients subjected to long-term TNF inhibitor therapy is mandatory.

PMID- 25581785
TI  - Propensity-matched comparison between Direct Flow Medical, Medtronic Corevalve,
      and Edwards Sapien XT prostheses: Device success, thirty-day safety, and
      mortality.
AB  - AIMS: To compare 30-day performance of three different type of transcatheter
      aortic valve implantation (TAVI) prosthesis: Direct Flow Medical (DFM), Medtronic
      Corevalve (MCV), and Edwards Sapien XT (ES). METHODS AND RESULTS: Forty
      consecutive patients treated with DFM for severe aortic stenosis were matched to
      an equal sample of patients undergoing TAVI with MCV and ES (1:1:1 propensity
      score-matching). Primary end-point was 30-day safety, defined according to the
      valve academic research consortium (VARC-2) criteria. Secondary end-points were:
      (i) immediate post-TAVI transaortic gradient reduction, (ii) device success, and
      (iii) 30-day mortality. Patients treated with DFM had higher 30-day safety rate
      compared to MCV and ES (respectively: 95.0% vs. 67.5% vs. 82.5%; P=0.006).
      Immediate post-TAVI, transaortic gradient reduction was similar for DFM, MCV, and
      ES subgroups (respectively: 8.3 +/- 5.2 mm Hg vs. 5.3 +/- 3.7 mm Hg vs. 5.6 +/-
      5.1 mm Hg; P=0.15); likewise, device success did not differ significantly
      (respectively: 100% vs. 92.5% vs. 92.5%; P=0.19). Mortality rates were also
      similar (respectively: 0% vs. 7.5% vs. 7.5%; P=0.190). In the pooled binary
      logistic regression analysis, blood transfusion was associated to 30-day safety
      (HR 0.156, 95% CI 0.049-0.500, P=0.002), while a significant trend was observed
      for the vascular closure device type (favoring Proglide vs. Prostar: HR 0.239,
      95% CI 0.049-1.160, P=0.076). CONCLUSIONS: In high-risk patients with aortic
      stenosis undergoing TAVI, device success and short-term mortality were comparable
      between DFM, MCV, and ES. In contrast, the 30-day VARC-defined safety primary end
      point was met significantly more frequently in patients treated with DFM. This
      result was mainly driven by differences in major vascular complications,
      associated to differences in vascular closure devices between the different valve
      subgroups.

PMID- 25581787
TI  - Morphological and mechanical imaging of Bacillus cereus spore formation at the
      nanoscale.
AB  - Bacteria from the genus Bacillus are able to transform into metabolically dormant
      states called (endo) spores in response to nutrient deprivation and other harsh
      conditions. These morphologically distinct spores are fascinating constructs,
      amongst the most durable cells in nature, and have attracted attention owing to
      their relevance in food-related illnesses and bioterrorism. Observing the course
      of bacterial spore formation (sporulation) spatially, temporally and
      mechanically, from the vegetative cell to a mature spore, is critical for a
      better understanding of this process. Here, we present a fast and versatile
      strategy for monitoring both the morphological and mechanical changes of Bacillus
      cereus bacteria at the nanoscale using atomic force microscopy. Through a
      strategy of imaging and nanomechanical mapping, we show the morphogenesis of the
      endospore and released mature endospore. Finally, we investigate individual
      spores to characterize their surface mechanically. The progression in elasticity
      coupled with a similarity of characteristic distributions between the incipient
      endospores and the formed spores show these distinct stages. Taken together, our
      data demonstrates the power of atomic force microscopy applied in microbiology
      for probing this important biological process at the single cell scale. 

PMID- 25581786
TI  - Sympathoadrenal neural crest cells: the known, unknown and forgotten?
AB  - Neural crest cells (NCCs) are highly migratory progenitor cells that give rise to
      a vast array of differentiated cell types. One of their key derivatives is the
      autonomic nervous system (ANS) that is comprised in part from chromaffin cells of
      the adrenal medulla and organ of Zuckerkandl, the sympathetic chain and
      additional prevertebral ganglia such as the celiac ganglia, suprarenal ganglia
      and mesenteric ganglia. In this review we discuss recent advances toward our
      understanding of how the NCC precursors of the ANS migrate to their target
      regions, how they are instructed to differentiate into the correct cell types,
      and the morphogenetic signals controlling their development. Many of these
      processes remain enigmatic to developmental biologists worldwide. Taking
      advantage of lineage tracing mouse models one of our own aims is to address the
      morphogenetic events underpinning the formation of the ANS and to identify the
      molecular mechanisms that help to segregate a mixed population of NCCs into
      pathways specific for the sympathetic ganglia, sensory ganglia or adrenal
      medulla. 

PMID- 25581788
TI  - Fascin expression in cholesteatoma: correlation with destruction of the ossicular
      chain and extent of disease.
AB  - OBJECTIVE: Fascin is an actin-bundling protein found in cell membrane protrusions
      and increases cell motility. The expression of fascin in epithelial neoplasms has
      been described only recently. No data are available concerning the role of this
      protein in invasive cholesteatoma. Thus, we investigated the expression of fascin
      in cholesteatoma tissue and the relationship between fascin expression and
      intraoperative evaluation of the destruction of the ossicular chain and extent of
      disease. METHOD: Cholesteatoma specimens of 28 patients and external auditory
      canal (EAC) skin specimens of the same patients (as the control group) were
      collected from mastoidectomies. Immunohistochemical technique was used to
      investigate the fascin expression in all cholesteatoma tissues and EAC skin
      specimens. Immunohistochemical staining was assessed semiquantitatively based on
      the thickness of epithelium. SPSS software version 16.0 (SPSS Inc., Chicago, IL,
      USA) was performed to statistically analyse the relationships between fascin
      expression and intraoperative evaluation destruction of ossicular chain and
      extent of the disease. RESULTS: Immunohistochemically, there was no or very low
      fascin expression observed in normal epithelial cells of EAC skin, while
      expressed in cholesteatoma tissue. Also, fascin expression in cholesteatoma
      tissues was significantly correlated with destruction of ossicular chain and
      extent of the disease. CONCLUSIONS: Fascin expression is usually found in
      cholesteatoma epithelium and is correlated with destruction of the ossicular
      chain and extent of disease. Considering all of the correlations between the
      clinical and histopathological findings, 'fascin immunoexpression scoring' may be
      used for histological grading of cholesteatoma.

PMID- 25581789
TI  - Longitudinal evaluation of effects of intra-articular mesenchymal stromal cell
      administration for the treatment of osteoarthritis in an ovine model.
AB  - In this study, the therapeutic effect of intra-articularly injected autologous
      mesenchymal stromal cells (MSCs) was evaluated in an ovine osteoarthritis (OA)
      model using consecutive magnetic resonance imaging (MRI), radiography, and
      macroscopic and histologic postmortem examination. In 12 sheep, OA was induced by
      bilateral, lateral meniscectomy. After 6 weeks, 20 * 10(6) bone marrow-derived
      MSCs (50% MSCs were superparamagnetic iron oxide particle labeled) were injected
      intra-articularly into one knee joint. The contralateral knee served as negative
      control. MR images were acquired before OA induction, immediately before and
      after MSC injection, and 1, 4, 8, and 12 weeks thereafter using a 0.5T unit and a
      T2* gradient echo sequence. Radiographs were obtained before OA induction, at MSC
      injection, and 12 weeks thereafter. The MRI scoring system included articular
      cartilage, bone, joint capsule, and synovial fluid evaluation. The radiographic
      scoring system included the joint space and bone. Postmortem evaluation entailed
      macroscopic and histologic assessment. Longitudinal MRI revealed a significant
      deceleration of OA progression in MSC-treated joints. However, at the conclusion
      of the study, there was no significant difference in the degree of OA detected by
      MRI, radiography, and postmortem evaluation between the treatment and control
      group. The degree of OA on MRI varied among the 12 animals at the time of
      injection, but there was no difference between the left and right limb. In
      conclusion, intra-articular MSCs decreased OA progression. However, no
      significant treatment effects were seen at the conclusion of the study at 12
      weeks. This somewhat contradicts previously published results. Nevertheless, the
      choice of OA model, outcome measures, or lack of additional medication might
      explain the differences. Our results indicate that OA might benefit from intra
      articular MSC injection, but further studies are needed to refine patient
      selection and injection parameters for a more substantially improved outcome. 

PMID- 25581790
TI  - Recognition determinants of broadly neutralizing human antibodies against dengue
      viruses.
AB  - Dengue disease is caused by four different flavivirus serotypes, which infect 390
      million people yearly with 25% symptomatic cases and for which no licensed
      vaccine is available. Recent phase III vaccine trials showed partial protection,
      and in particular no protection for dengue virus serotype 2 (refs 3, 4).
      Structural studies so far have characterized only epitopes recognized by serotype
      specific human antibodies. We recently isolated human antibodies potently
      neutralizing all four dengue virus serotypes. Here we describe the X-ray
      structures of four of these broadly neutralizing antibodies in complex with the
      envelope glycoprotein E from dengue virus serotype 2, revealing that the
      recognition determinants are at a serotype-invariant site at the E-dimer
      interface, including the exposed main chain of the E fusion loop and the two
      conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding
      site for the viral glycoprotein prM during virus maturation in the secretory
      pathway of the infected cell, explaining its conservation across serotypes and
      highlighting an Achilles' heel of the virus with respect to antibody
      neutralization. These findings will be instrumental for devising novel immunogens
      to protect simultaneously against all four serotypes of dengue virus. 

PMID- 25581798
TI  - Osteichthyan-like cranial conditions in an Early Devonian stem gnathostome.
AB  - The phylogeny of Silurian and Devonian (443-358 million years (Myr) ago) fishes
      remains the foremost problem in the study of the origin of modern gnathostomes
      (jawed vertebrates). A central question concerns the morphology of the last
      common ancestor of living jawed vertebrates, with competing hypotheses advancing
      either a chondrichthyan- or osteichthyan-like model. Here we present Janusiscus
      schultzei gen. et sp. nov., an Early Devonian (approximately 415 Myr ago)
      gnathostome from Siberia previously interpreted as a ray-finned fish, which
      provides important new information about cranial anatomy near the last common
      ancestor of chondrichthyans and osteichthyans. The skull roof of Janusiscus
      resembles that of early osteichthyans, with large plates bearing vermiform ridges
      and partially enclosed sensory canals. High-resolution computed tomography (CT)
      reveals a braincase bearing characters typically associated with either
      chondrichthyans (large hypophyseal opening accommodating the internal carotid
      arteries) or osteichthyans (facial nerve exiting through jugular canal,
      endolymphatic ducts exiting posterior to the skull roof) but lacking a ventral
      cranial fissure, the presence of which is considered a derived feature of crown
      gnathostomes. A conjunction of well-developed cranial processes in Janusiscus
      helps unify the comparative anatomy of early jawed vertebrate neurocrania,
      clarifying primary homologies in 'placoderms', osteichthyans and chondrichthyans.
      Phylogenetic analysis further supports the chondrichthyan affinities of
      'acanthodians', and places Janusiscus and the enigmatic Ramirosuarezia in a
      polytomy with crown gnathostomes. The close correspondence between the skull roof
      of Janusiscus and that of osteichthyans suggests that an extensive dermal
      skeleton was present in the last common ancestor of jawed vertebrates, but
      ambiguities arise from uncertainties in the anatomy of Ramirosuarezia. The
      unexpected contrast between endoskeletal structure in Janusiscus and its
      superficially osteichthyan-like dermal skeleton highlights the potential
      importance of other incompletely known Siluro-Devonian 'bony fishes' for
      reconstructing patterns of trait evolution near the origin of modern
      gnathostomes. 

PMID- 25581794
TI  - Mechanistic insights into the recycling machine of the SNARE complex.
AB  - Evolutionarily conserved SNARE (soluble N-ethylmaleimide sensitive factor
      attachment protein receptors) proteins form a complex that drives membrane fusion
      in eukaryotes. The ATPase NSF (N-ethylmaleimide sensitive factor), together with
      SNAPs (soluble NSF attachment protein), disassembles the SNARE complex into its
      protein components, making individual SNAREs available for subsequent rounds of
      fusion. Here we report structures of ATP- and ADP-bound NSF, and the
      NSF/SNAP/SNARE (20S) supercomplex determined by single-particle electron
      cryomicroscopy at near-atomic to sub-nanometre resolution without imposing
      symmetry. Large, potentially force-generating, conformational differences exist
      between ATP- and ADP-bound NSF. The 20S supercomplex exhibits broken symmetry,
      transitioning from six-fold symmetry of the NSF ATPase domains to pseudo four
      fold symmetry of the SNARE complex. SNAPs interact with the SNARE complex with an
      opposite structural twist, suggesting an unwinding mechanism. The interfaces
      between NSF, SNAPs, and SNAREs exhibit characteristic electrostatic patterns,
      suggesting how one NSF/SNAP species can act on many different SNARE complexes. 

PMID- 25581799
TI  - Fixation-resistant photoactivatable fluorescent proteins for CLEM.
AB  - Fluorescent proteins facilitate a variety of imaging paradigms in live and fixed
      samples. However, they lose their fluorescence after heavy fixation, hindering
      applications such as correlative light and electron microscopy (CLEM). Here we
      report engineered variants of the photoconvertible Eos fluorescent protein that
      fluoresce and photoconvert normally in heavily fixed (0.5-1% OsO4), plastic resin
      embedded samples, enabling correlative super-resolution fluorescence imaging and
      high-quality electron microscopy. 

PMID- 25581803
TI  - From the ASTDA.

PMID- 25581800
TI  - Improved and expanded Q-system reagents for genetic manipulations.
AB  - The Q system is a repressible binary expression system for transgenic
      manipulations in living organisms. Through protein engineering and in vivo
      functional tests, we report here variants of the Q-system transcriptional
      activator, including QF2, for driving strong and ubiquitous expression in all
      Drosophila tissues. Our QF2, Gal4QF and LexAQF chimeric transcriptional
      activators substantially enrich the toolkit available for transgenic regulation
      in Drosophila melanogaster. 

PMID- 25581804
TI  - Female partner notification is a promising prevention strategy for controlling
      sexually transmitted infections in Shanghai: demographic and behavioral data from
      a Shanghai clinic.
AB  - We identified predictors of partner presentation and condom use among male
      gonorrhea patients in Shanghai, China. Stable relationships, intercourse in the
      preceding week, and longer duration of symptoms were associated with partner
      presentation. Men were more likely to use condoms with their spouse and if they
      were 35 years or younger. 

PMID- 25581801
TI  - Targeted exploration and analysis of large cross-platform human transcriptomic
      compendia.
AB  - We present SEEK (search-based exploration of expression compendia;
      http://seek.princeton.edu/), a query-based search engine for very large
      transcriptomic data collections, including thousands of human data sets from many
      different microarray and high-throughput sequencing platforms. SEEK uses a query
      level cross-validation-based algorithm to automatically prioritize data sets
      relevant to the query and a robust search approach to identify genes, pathways
      and processes co-regulated with the query. SEEK provides multigene query
      searching with iterative metadata-based search refinement and extensive
      visualization-based analysis options. 

PMID- 25581805
TI  - Deriving and validating a risk estimation tool for screening asymptomatic
      chlamydia and gonorrhea.
AB  - BACKGROUND: There has been considerable interest in the development of innovative
      service delivery modules for prioritizing resources in sexual health delivery in
      response to dwindling fiscal resources and rising infection rates. METHODS: This
      study aims to derive and validate a risk scoring algorithm to accurately identify
      asymptomatic patients at increased risk for chlamydia and/or gonorrhea infection.
      We examined the electronic records of patient visits at sexual health clinics in
      Vancouver, Canada. We derived risk scores from regression coefficients of
      multivariable logistic regression model using visits between 2000 and 2006. We
      evaluated the model's discrimination, calibration, and screening performance.
      Temporal validation was assessed in visits from 2007 to 2012. RESULTS: The
      prevalence of infection was 1.8% (n = 10,437) and 2.1% (n = 14,956) in the
      derivation and validation data sets, respectively. The final model included
      younger age, nonwhite ethnicity, multiple sexual partners, and previous infection
      and showed reasonable performance in the derivation (area under the receiver
      operating characteristic curve = 0.74; Hosmer-Lemeshow P = 0.91) and validation
      (area under the receiver operating characteristic curve = 0.64; Hosmer-Lemeshow P
      = 0.36) data sets. A risk score cutoff point of at least 6 detected 91% and 83%
      of cases by screening 68% and 68% of the derivation and validation populations,
      respectively. CONCLUSIONS: These findings support the use of the algorithm for
      individualized risk assessment and have important implications for reducing
      unnecessary screening and saving costs. Specifically, we anticipate that the
      algorithm has potential uses in alternative settings such as Internet-based
      testing contexts by facilitating personalized test recommendations, stimulating
      health care-seeking behavior, and aiding risk communication by increasing
      sexually transmitted infection risk perception through the creation of tailored
      risk messages to different groups.

PMID- 25581806
TI  - Etiology and antimicrobial susceptibility of pathogens responsible for urethral
      discharge among men in Harare, Zimbabwe.
AB  - BACKGROUND: Periodic etiological surveillance of sexually transmitted infection
      (STI) syndromes is required to validate treatment algorithms used to control
      STIs. However, such surveys have not been performed in Zimbabwe over the past
      decade. METHODS: A cross-sectional study design was used to determine the
      prevalence of the key STI etiological agents causing male urethral discharge
      (MUD). Urethral swab specimens were collected for molecular analysis and
      Neisseria gonorrhoeae isolation from consenting men 18 years and older who
      presented with MUD to the 12 clinics in Harare, Zimbabwe, between November 2010
      and May 2011. A validated in-house multiplex polymerase chain reaction assay was
      used to detect the presence of N. gonorrhoeae, Chlamydia trachomatis, Trichomonas
      vaginalis, and Mycoplasma genitalium. Gonococci were cultured on selective media,
      and antimicrobial susceptibilities were determined locally for ciprofloxacin,
      kanamycin, ceftriaxone, and cefixime using Etest strips, and minimum inhibitory
      concentrations were reported using defined breakpoints. RESULTS: Among 130
      participants, N. gonorrhoeae was the most frequent pathogen detected (106;
      82.8%), followed by C. trachomatis (15; 11.7%), M. genitalium (6; 4.7%), and T.
      vaginalis (2; 1.6%). Four (6.1%) of the 66 gonococci isolated were resistant to
      fluoroquinolones, whereas all viable isolates were susceptible to kanamycin,
      cefixime, and ceftriaxone. CONCLUSIONS: Gonorrhea is the most important cause of
      MUD in men in Harare, and our study highlights the emergence of fluoroquinolone
      resistant N. gonorrhoeae. Further STI surveys are required in other regions of
      Zimbabwe to obtain a nationally representative picture of gonococcal burden and
      antimicrobial resistance among MUD patients.

PMID- 25581807
TI  - The antimicrobial effect of boric acid on Trichomonas vaginalis.
AB  - BACKGROUND: The treatment options for trichomoniasis are largely limited to
      nitroimidazole compounds (metronidazole and tinidazole). Few alternatives exist
      in cases of recalcitrant infections or in cases of nitroimidazole
      hypersensitivity. Recently, the intravaginal administration of boric acid has
      been advocated as an alternative treatment of trichomoniasis. However, no in
      vitro studies are available that directly assess the sensitivity of Trichomonas
      vaginalis to boric acid. METHODS: We examined the sensitivity of common
      laboratory strains and recent clinical isolates of T. vaginalis to boric acid.
      The effect of increasing concentrations of boric acid on parasite growth and
      viability was determined, and a minimal lethal concentration was reported. The
      effect of pH on boric acid toxicity was assessed and compared with that of lactic
      and acetic acid. RESULTS: Boric acid is microbicidal to T. vaginalis, and its
      antitrichomonal activity is independent of environmental acidification. Unlike
      acetic acid and lactic acid, boric acid exposure results in growth suppression
      and lethality over a wide range of pH (5-7) and under conditions that are
      normally permissible for growth in vitro. CONCLUSIONS: The microbicidal effect of
      boric acid on T. vaginalis, coupled with its previous clinical use in treating
      vaginal candidiasis, supports the continued inclusion of boric acid in the
      therapeutic arsenal for treating trichomoniasis.

PMID- 25581809
TI  - Identification of demographic and behavioral risk factors for antibiotic
      resistant gonorrhea infections to combat the emergence of potentially untreatable
      infections.

PMID- 25581811
TI  - Comparison of visual and ultraviolet light inspection versus DNA/protein
      biomarkers to assess product adherence with vaginal microbicide applicators.
AB  - BACKGROUND: Objective biomarkers of product use and protocol compliance are
      urgently needed. We compared the sensitivity and specificity of DNA and protein
      based biomarkers, obtained from used vaginal gel applicators, to visual
      inspection of those applicators under ambient light (visual inspection of
      returned applicator [VIRA]) and ultraviolet light (UVL). METHODS: Forty women
      inserted hydroxyethylcellulose placebo gel vaginal applicators under direct
      observation. Applicators were evaluated by VIRA, UVL, and DNA/protein-based
      methods at 2 time points: within 7 days of the visit and after storing
      applicators for approximately 30 days. Semen biomarkers were assayed from vaginal
      swabs and returned applicators. RESULTS: The overall sensitivity and specificity
      of DNA and protein-based biomarkers in determining vaginal insertion versus sham
      handling of returned applicators were 98.3% and 100%, respectively, at both 7-
      and 30-day evaluations. The overall sensitivity and specificity of VIRA at 7 and
      30 days after collection were significantly lower than those of DNA and protein
      based biomarkers. Ultraviolet light inspection also had significantly lower
      overall sensitivity and overall specificity compared with DNA and protein
      biomarkers. The sensitivity of DNA and protein-based biomarkers for detecting
      insertion of wiped applicators was 95%, whereas the sensitivity of VIRA (range of
      24%-28%) and UVL inspection (range, 38%-84%) was low for this subset. It was
      feasible to obtain semen biomarkers from vaginal swabs and returned used
      applicators. CONCLUSIONS: DNA and protein-based biomarkers offer significantly
      higher sensitivity and specificity compared with VIRA and UVL assessment. The
      accuracy of these objective biomarkers is maintained despite storage of returned
      products for approximately 30 days and under conditions potentially modeling
      field use.

PMID- 25581808
TI  - Risk factors for antimicrobial-resistant Neisseria gonorrhoeae in Europe.
AB  - BACKGROUND: The European Gonococcal Antimicrobial Surveillance Programme performs
      antimicrobial resistance surveillance and is coordinated by the European Centre
      for Disease Prevention and Control. This study used epidemiological and
      behavioral data combined with the gonococcal susceptibility profiles to determine
      risk factors associated with harboring resistant gonococci in Europe. METHODS:
      From 2009 to 2011, gonococcal isolates from 21 countries were submitted to the
      European Gonococcal Antimicrobial Surveillance Programme for antimicrobial
      susceptibility testing. Patient variables associated with resistance to
      azithromycin, cefixime, and ciprofloxacin were identified using univariate and
      multivariable logistic regression analyses of odds ratios. Geometric means for
      ceftriaxone and cefixime minimum inhibitory concentrations (MICs) were compared
      for patients of different sexual orientation and sex. RESULTS: A total of 5034
      gonococcal isolates were tested from 2009 to 2011. Isolates exhibiting resistance
      to cefixime (MIC > 0.125 mg/L) and ciprofloxacin (MIC > 0.5 mg/L) were
      significantly associated with infection in heterosexuals (males only for
      ciprofloxacin), older patients (>25 years of age), or those without a concurrent
      chlamydial infection in the multivariable analysis. The geometric mean of
      cefixime and ceftriaxone MICs decreased from 2009 to 2011, most significantly for
      men who have sex with men, and isolates from male heterosexuals exhibited the
      highest MICs in 2011. CONCLUSIONS: The linking of epidemiological and behavioral
      data to the susceptibility profiles of the gonococcal isolates has allowed those
      at higher risk for acquiring antimicrobial resistant Neisseria gonorrhoeae to be
      identified. Improved data numbers and representativeness are required before
      evidence-based risk groups can be identified, and subsequent focused treatments
      or public health intervention strategies can be initiated with confidence.

PMID- 25581810
TI  - Prevalence of human papillomavirus infection in Guangdong Province, China: a
      population-based survey of 78,355 women.
AB  - BACKGROUND: The prevalence of human papillomavirus (HPV) infection and the
      distribution of different HPV genotypes vary greatly within different
      geographical and ethnic populations, especially in Asia. The HPV infection data
      based on regional population are extremely important for researchers to develop
      new efficient HPV screening assays and estimate the effect of vaccines on
      preventing from cervical cancer. METHODS: A total of 78,355 women from Guangdong
      Province, China, whose ages were from 18 to 75 years were enrolled in this study.
      All epidemiological data were obtained by face-to-face interview. Cervical
      exfoliated cells were collected, and HPV-DNA test was conducted with the matrix
      assisted laser desorption/ionization time-of flight mass spectrometry. RESULTS:
      The overall HPV infection prevalence in the study population was 7.3%. The top 6
      HPV genotypes were HPV16 (1.5%), HPV52 (1.2%), HPV58 (1.0%), HPV18 (0.7%), HPV45
      (0.5%), and HPV6 (0.5%), accounting for 69.7% of all detected HPV infection
      types. Two peaks of HPV infection were detected in the population of old age
      group (>50; 9.6%) and young group (<25; 8.2%). Infection with single genotype HPV
      (6.2% in all; 85.7% in HPV-positive women) was more frequent than infection with
      multiple HPV (1.0% and 14.3% respectively). Results of multivariate logistic
      regression revealed that sexual active years, numbers of sexual partner, and
      numbers of pregnancy were risk factors of HPV infection. CONCLUSIONS: This study
      provides useful epidemiological information on cervical HPV infection prevalence
      in general female population from Guangdong Province, China. In this population,
      HPV infection prevalence was 7.3%, and genotypes HPV16, HPV52, and HPV58 showed a
      relatively high prevalence.

PMID- 25581812
TI  - Disseminated gonococcal infection and eculizumab--a "high risk" connection?
AB  - A 28-year-old woman who was undergoing treatment with eculizumab for paroxysmal
      nocturnal hemoglobinuria presented to the hospital with fevers, chills, headache,
      and a swollen left index finger. Blood cultures returned positive for Neisseria
      gonorrhoeae. We report the second case of disseminated gonococcal infection
      associated with the use of eculizumab. 

PMID- 25581813
TI  - Anal intercourse without condoms among HIV-positive men who have sex with men
      recruited from a sexual networking web site, United States.
AB  - BACKGROUND: The changing landscape of HIV prevention in the United States
      underscores the need to improve our ability to efficiently reach HIV-positive men
      who have sex with men (MSM) who engage in behaviors that could transmit HIV.
      METHODS: We examined the prevalence of anal intercourse (AI) without condoms with
      HIV-negative or unknown serostatus partners ("at-risk partners") among 1319 HIV
      positive adult male members of a sexual networking Web site for MSM. Sexual
      behaviors and substance use were measured over a 60-day recall period. Logistic
      regression was used to identify correlates of insertive and receptive AI without
      condoms with at-risk partners. RESULTS: Approximately 25% of the men had been
      diagnosed as having HIV 12 months or less before study enrollment. Overall, 32%
      of men engaged in AI without condoms with at-risk partners. Multiple logistic
      regression identified behavioral predictors of insertive AI without condoms with
      at-risk partners, including HIV diagnosis within the last 12 months, sex with
      multiple male partners, substance use in conjunction with sex, and use of
      phosphodiesterase type 5 inhibitors. Receptive AI without condoms with at-risk
      partners was associated with younger age (19-24 years), residing outside
      metropolitan cities, substance use in conjunction with sex, and having multiple
      male partners. CONCLUSIONS: High levels of sexual risk were found among these
      MSM. Increased Internet-based HIV prevention marketing efforts and prevention
      strategies should be considered to efficiently reach HIV-positive MSM who engage
      in serodiscordant AI without condoms.

PMID- 25581814
TI  - Using virtual spaces to engage HIV-positive men who have sex with men online:
      considerations for future research and interventions.

PMID- 25581815
TI  - Population pharmacokinetics of tenofovir and tenofovir-diphosphate in healthy
      women.
AB  - The objective of this analysis was to develop and qualify a population
      pharmacokinetic model describing plasma tenofovir (TFV) concentrations and
      tenofovir-diphosphate (TFV-DP) concentrations in peripheral blood mononuclear
      cell (PBMC) in healthy women volunteers from the MTN-001 clinical trial, an open
      label 3-way crossover study of oral tenofovir disoproxil fumarate 300 mg tablet,
      TFV 1% vaginal gel, or both. TFV pharmacokinetics were best described by a 2
      compartment, first-order absorption/elimination model with absorption lag time.
      TFV was linked to PBMC TFV-DP by first-order uptake with first-order elimination.
      An adherence adjustment was included to account for nonadherence by explicitly
      modeling a bioavailability parameter on the previous day's dose. The final model
      included weight as a covariate on central compartment volume (Vc ) with estimates
      as follows: absorption rate constant (Ka) 9.79 h(-1) , absorption lag time 0.5
      hours, Vc 385.71-2.16*(73-WT(kg)), and apparent TFV clearance of 56.7 L/h ((K20 +
      K24)*Vc ). TFV-DP's half-life was 53.3 hours. All diagnostic plots and bootstrap
      confidence intervals were acceptable. Model validation was conducted using
      simulations compared to data from the MTN-001 oral + vaginal period and other
      clinical trial data. The resulting model closely predicted the disposition of TFV
      and TFV-DP when compared to healthy participant data from another clinical trial.

PMID- 25581816
TI  - Hepatocellular carcinoma surveillance rates in commercially insured patients with
      noncirrhotic chronic hepatitis B.
AB  - American association for the study of liver diseases (AASLD) and European
      Association for the Study of the Liver (EASL) guidelines recommend biannual
      hepatocellular carcinoma (HCC) screening for noncirrhotic patients with chronic
      hepatitis B infection (HBV), yet there are no data estimating surveillance rates
      or factors associated with surveillance. We performed a retrospective cohort
      study of US patients using the Truven Health Analytics databases from 2006 to
      2010 and identified patients with noncirrhotic chronic HBV. Surveillance patterns
      were characterized using categorical and continuous outcomes, with the continuous
      measure of the proportion of time 'up to date' with surveillance (PUTDS), with
      the 6-month interval following each ultrasound categorized as 'up to date'.
      During a median follow-up of 26.0 (IQR: 16.2-40.0) months among 4576 noncirrhotic
      patients with chronic HBV (median age: 44 years, IQR: 36-52), only 306 (6.7%) had
      complete surveillance (one ultrasound every 6-month interval), 2727 (59.6%)
      incomplete (>=1 ultrasound) and 1543 (33.7%) none. The mean PUTDS was 0.34 +/-
      0.29, and the median was 0.32 (IQR: 0.03-0.52). In multinomial logistic
      regression models, patients diagnosed by a nongastroenterologist were
      significantly less likely to have complete surveillance (P < 0.001), as were
      those coinfected with HBV/HIV (P < 0.001). In linear regression models,
      nongastroenterologist provider, health insurance subtype, HBV/HIV coinfection,
      rural status and metabolic syndrome were independently associated with decreased
      surveillance. Patients with HIV had an absolute decrease in the PUTDS of 0.24,
      while patients in less populated rural areas had an absolute decrease of 0.10.
      HCC surveillance rates in noncirrhotic patients with chronic HBV in the United
      States are poor and lower than reported rates of HCC surveillance in cirrhotic
      patients.

PMID- 25581817
TI  - Preliminary Study on Prevalence, Risk Factor and Genetic Homogeneity of Porcine
      Reproductive and Respiratory Syndrome Virus in Registered Pig Farms in
      Heilongjiang, China.
AB  - While porcine reproductive and respiratory syndrome (PRRS) causes great economic
      losses in southern and central China, systematic studies on the epidemiology of
      PRRS virus (PRRSV) in Heilongjiang Province had not been performed. Therefore, we
      conducted a preliminary study to estimate the prevalence and risk factors
      associated with PRRSV infection, as well as characterize the PRRSV in registered
      pig farms in Heilongjiang Province, China in 2011. A total of 1237 blood samples
      were collected from 72 farms and tested by reverse transcription polymerase chain
      reaction (RT-PCR) for PRRSV. Risk factors associated to PRRSV infection were
      analysed using logistic regression models. Genes of non-structural protein-2
      (Nsp2) and glycoprotein 5 (GP5) from 22 isolates were sequenced for phylogenetic
      analysis. The results showed that the herd apparent prevalence was 9.7% (95% CI:
      6.3, 13.1) in Heilongjiang Province. An increased risk of PRRSV infection on
      farms was associated with unrestricted movement of external people (OR = 14.1,
      95% CI: 1.68, 119.07), close proximity (<1 km) to the nearest house, road or
      neighbouring farm (OR = 16.2, 95% CI: 1.52, 171.80), and selling farm products at
      both local and provincial markets (OR = 20.6, 95% CI: 2.02, 210.56). Phylogenetic
      analysis based on partial amino acid sequences of GP5 and Nsp2 showed that all
      the 22 PRRSV isolates in Heilongjiang are closely related to the highly
      pathogenic PRRSV strain JXA1 and belong to the Genotype 2 (American genotype).
      The prevalence, determination of risk factors and phylogenetic characterization
      will provide information for future epidemiological studies and a reference for
      developing surveillance and control strategies in this region. 

PMID- 25581819
TI  - Super-resolution imaging for cell biologists: concepts, applications, current
      challenges and developments.
AB  - The recent 2014 Nobel Prize in chemistry honored an era of discoveries and
      technical advancements in the field of super-resolution microscopy. However, the
      applications of diffraction-unlimited imaging in biology have a long road ahead
      and persistently engage scientists with new challenges. Some of the bottlenecks
      that restrain the dissemination of super-resolution techniques are tangible, and
      include the limited performance of affinity probes and the yet not capillary
      diffusion of imaging setups. Likewise, super-resolution microscopy has introduced
      new paradigms in the design of projects that require imaging with nanometer
      resolution and in the interpretation of biological images. Besides structural or
      morphological characterization, super-resolution imaging is quickly expanding
      towards interaction mapping, multiple target detection and live imaging. Here we
      review the recent progress of biologists employing super-resolution imaging, some
      pitfalls, implications and new trends, with the purpose of animating the field
      and spurring future developments. 

PMID- 25581820
TI  - Accumulation of Trace Metals by Mangrove Plants in Indian Sundarban Wetland:
      Prospects for Phytoremediation.
AB  - The work investigates on the potential of ten mangrove species for absorption,
      accumulation and partitioning of trace metal(loid)s in individual plant tissues
      (leaves, bark and root/pneumatophore) at two study sites of Indian Sundarban
      Wetland. The metal(loid) concentration in host sediments and their geochemical
      characteristics were also considered. Mangrove sediments showed unique potential
      in many- fold increase for most metal(loid)s than plant tissues due to their
      inherent physicochemical properties. The ranges of concentration of trace
      metal(loid)s for As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb and Zn in plant tissue
      were 0.006-0.31, 0.02-2.97, 0.10-4.80, 0.13-6.49, 4.46-48.30, 9.2-938.1, 0.02
      0.13, 9.8-1726, 11-5.41, 0.04-7.64, 3.81-52.20 MUg g (-1)respectively. The bio-
      concentration factor (BCF) showed its maximum value (15.5) in Excoecaria
      agallocha for Cd, suggesting that it can be considered as a high-efficient plant
      for heavy metal bioaccumulation. Among all metals, Cd and Zn were highly
      bioaccumulated in E. agallocha (2.97 and 52.2 MUg g (-1) respectively. Our
      findings suggest that the species may be classified as efficient metal trap for
      Cd in aerial parts, as indicated by higher metal accumulation in the leaves
      combined with BCF and translocation factor (TF) values.

PMID- 25581818
TI  - Interactions between mitochondria and the transcription factor myocyte enhancer
      factor 2 (MEF2) regulate neuronal structural and functional plasticity and
      metaplasticity.
AB  - The classical view of mitochondria as housekeeping organelles acting in the
      background to simply maintain cellular energy demands has been challenged by
      mounting evidence of their direct and active participation in synaptic plasticity
      in neurons. Time-lapse imaging has revealed that mitochondria are motile in
      dendrites, with their localization and fusion and fission events regulated by
      synaptic activity. The positioning of mitochondria directly influences function
      of nearby synapses through multiple pathways including control over local
      concentrations of ATP, Ca(2+) and reactive oxygen species. Recent studies have
      also shown that mitochondrial protein cascades, classically associated with
      apoptosis, are involved in neural plasticity in healthy cells. These findings
      link mitochondria to the plasticity- and metaplasticity-associated activity
      dependent transcription factor myocyte enhancer factor 2 (MEF2), further
      repositioning mitochondria as potential command centres for regulation of
      synaptic plasticity. Intriguingly, MEF2 and mitochondrial functions appear to be
      intricately intertwined, as MEF2 is a target of mitochondrial apoptotic caspases
      and, in turn, MEF2 regulates mitochondrial genome transcription essential for
      production of superoxidase and hydrogen peroxidase. Here, we review evidence
      supporting mitochondria as central organelles controlling the spatiotemporal
      expression of neuronal plasticity, and attempt to disentangle the MEF2
      mitochondria relationship mediating these functions. 

PMID- 25581821
TI  - Novel function of histamine signaling in hyperlipidemia-induced atherosclerosis:
      Histamine H1 receptors protect and H2 receptors accelerate atherosclerosis.
AB  - Histamine is not only essential for acute inflammatory reactions, but it also
      participates in a chronic inflammatory disorder. We generated apolipoprotein E
      (apoE) and histamine receptors (HHRs), including the major H1 and H2 receptors
      (HH1R, HH2R) double knockout mice (DKO) to clarify the role of HHRs in
      hyperlipidemia-induced atherosclerosis, in which apoE-KO and DKO mice were fed a
      high cholesterol diet. We found that pronounced hyperlipidemia-induced
      atherosclerotic progression occurred in HH1R/apoE-DKO mice, but in HH2R/apoE-DKO
      mice less atherosclerosis, despite pro-atherogenic serum cholesterol levels
      compared with apoE-KO mice. Furthermore, the increased expressions of scavenger
      receptors (SRs), such as SR-A, CD36 and lectin-like oxidized low-density
      lipoprotein receptor 1 (LOX-1), nuclear factor-kappa B (NFkappaB), monocyte
      chemoattractant protein (MCP-1), matrix metalloproteinases (MMPs) or liver X
      receptor (LXR)-related inflammatory signaling factors, were consistent with the
      pro-atherogenic phenotype of HH2R/apoE-DKO mice. We hypothesize that
      histamine/HH1R and HH2R signaling has conflicting innate functions,
      inflammatory/atherogenic and anti-inflammatory/anti-atherogenic actions, and that
      there are innate links between histamine signaling and hyperlipidemia-induced
      atherosclerosis, independently of serum cholesterol metabolism. Specific
      histamine signaling blockers, in particular, HH2R blockers, are a possible novel
      therapeutic target for hyperlipidemia-induced atherosclerosis. 

PMID- 25581822
TI  - Is CD10 antibody useful in the diagnosis of angioimmunoblastic T-cell lymphoma?
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is a rare lymphoma accounting for less
      than 1% of non Hodgkin lymphomas. The lack of specific clinical and histologic
      features in addition to the multiplicity of morphologic mimickers makes the
      diagnosis challenging. Some authors reported the utility of CD10 antibody as a
      diagnostic marker. Our aim is to explore the value of this marker through a
      presentation of a study about four cases diagnosed over a six-year-period and a
      mini-review of the literature. We present a study of 4 cases of AITL diagnosed in
      lymph node biopsies. Microscopic findings showed in all cases early AITL
      characterized by a pattern I. The diagnosis of AITL was made in all cases based
      on the morphologic and immunohistochemical features. The CD3 antibody was
      expressed in all cases but CD10 antibody was negative in all cases. All the
      patients died and the initiation of a conventional chemotherapy wasn't possible
      in all cases because of the rapid course of the disease. Because of the small
      number of our cases, we can't rule out a possible diagnostic value of CD10 but
      its negativity in all our cases makes us doubt its sensitivity. 

PMID- 25581824
TI  - Effect of genetic deletion or pharmacological antagonism of tumor necrosis factor
      alpha on colitis-associated carcinogenesis in mice.
AB  - BACKGROUND: Intestinal inflammation in inflammatory bowel diseases is driven by
      abnormal levels of proinflammatory cytokines, where tumor necrosis factor (TNF)
      alpha seems to be particularly important. Chronic inflammatory signaling in the
      colon increases the risk of colorectal cancer, so we sought to evaluate the role
      of TNF-alpha in a mouse model of this condition. METHODS: TNF mice were treated
      with azoxymethane/dextran sulfate sodium to induce inflammation and
      tumorigenesis. Etanercept was used to produce pharmacological ablation of TNF
      alpha in wild-type mice. Subsequent activation of procarcinogenic transcription
      factor NF-kappaB and relevant proinflammatory cytokines of the TNF superfamily
      were measured through immunohistochemistry and quantitative polymerase chain
      reaction methods. RESULTS: Results showed that the severity of colitis, as
      assessed by mortality, histological scoring, and cytokine expression levels, was
      similar or slightly higher in mice lacking TNF-alpha than in control mice.
      Activation levels of NF-kappaB were not influenced by the presence of TNF-alpha.
      We also observed upregulated expression of TNF family member TNF-beta, TNF
      receptors 1 and 2 and a variety of other proinflammatory factors in colitis
      associated tumors of TNF mice, compared with levels in tumors of control mice.
      Neither genetic ablation of TNF-alpha nor pharmacological inhibition of the TNF
      family using etanercept reduced tumor number. CONCLUSIONS: Our results reveal a
      redundant role for TNF-alpha in a mouse model of colitis-associated
      tumorigenesis, indicating a high degree of redundancy in proinflammatory cytokine
      networks in this model.

PMID- 25581823
TI  - In vivo imaging models of bone and brain metastases and pleural carcinomatosis
      with a novel human EML4-ALK lung cancer cell line.
AB  - EML4-ALK lung cancer accounts for approximately 3-7% of non-small-cell lung
      cancer cases. To investigate the molecular mechanism underlying tumor progression
      and targeted drug sensitivity/resistance in EML4-ALK lung cancer, clinically
      relevant animal models are indispensable. In this study, we found that the lung
      adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a,
      E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib. We
      further established highly tumorigenic A925LPE3 cells, which also have the EML4
      ALK gene fusion (variant 5a) and are sensitive to ALK inhibitors. By using
      A925LPE3 cells with luciferase gene transfection, we established in vivo imaging
      models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of
      which are significant clinical concerns of advanced EML4-ALK lung cancer.
      Interestingly, crizotinib caused tumors to shrink in the pleural carcinomatosis
      model, but not in bone and brain metastasis models, whereas alectinib showed
      remarkable efficacy in all three models, indicative of the clinical efficacy of
      these ALK inhibitors. Our in vivo imaging models of multiple organ sites may
      provide useful resources to analyze further the pathogenesis of EML4-ALK lung
      cancer and its response and resistance to ALK inhibitors in various organ
      microenvironments. 

PMID- 25581825
TI  - Testing for Clostridium difficile in patients newly diagnosed with inflammatory
      bowel disease in a community setting.
AB  - BACKGROUND: The incidence of Clostridium difficile infection (CDI) in
      inflammatory bowel disease (IBD) is increasing, and CDI has a negative impact on
      IBD outcomes with both increased morbidity and mortality. Data are lacking
      regarding the rate of appropriate testing for CDI at the time of diagnosis.
      METHODS: We sought to determine the rate of CDI testing and CDI positivity at
      diagnosis of IBD using data collected through the Ocean State Crohn's and Colitis
      Area Registry (OSCCAR), a prospective cohort of patients with newly diagnosed
      IBD. CDI testing and CDI positivity were determined by reviewing the medical
      records of patients enrolled into the registry and diagnosed with IBD between
      January 2008 and July 2011. RESULTS: Of 320 enrolled patients, 227 (70.9%)
      reported diarrhea, and CDI testing was performed for 113 (49.8%) of the 227
      patients. CDI testing was not recorded as being performed for the remaining 114
      patients who reported having diarrhea. An additional 24 patients were tested for
      CDI but did not report having diarrhea. Seven (5.1%) of the 137 patients tested
      for CDI were positive. CONCLUSIONS: Testing for CDI is significantly lower than
      expected at diagnosis of IBD. Although the prevalence of CDI among tested
      patients is approximately 5%, a low testing rate suggests a significant quality
      issue in the diagnosis of IBD, with the potential for delayed diagnosis of CDI.

PMID- 25581827
TI  - Endoplasmic reticulum stress and unfolded protein response in inflammatory bowel
      disease.
AB  - In eukaryotic cells, protein folding and modification in the endoplasmic
      reticulum (ER) is highly sensitive to disturbances of homeostasis. The
      accumulation of unfolded and misfolded proteins in the ER lumen, termed ER
      stress, activates intracellular signaling pathways to resolve the protein-folding
      defect. This unfolded protein response (UPR) increases the capacity of ER protein
      folding, reduces global protein synthesis, and activates ER-associated protein
      degradation. If ER stress is too severe or chronic, or the UPR is compromised and
      not able to restore ER protein-folding homeostasis, numerous apoptotic signaling
      pathways are activated. Preclinical and clinical studies in the past decade
      indicate that ER stress and the UPR have a significant impact on the pathogenesis
      of inflammatory bowel disease. Paneth and goblet cells, 2 epithelial cell
      populations in the gut, rely on a robust ER function for protein folding and
      secretion. Several immune cells are orchestrated by ER stress and the UPR for
      differentiation, activation, migration, and survival. In addition, a variety of
      exogenous and endogenous molecules in the intestinal lumen affect ER function,
      making ER stress and the UPR relevant cellular signals in intestinal homeostasis.
      Recent studies demonstrated that unresolved ER stress and/or dysregulated UPR may
      cause inflammatory bowel disease by inducing epithelial cell death, impairing
      mucosal barrier function, and activating proinflammatory response in the gut.
      With our increased understanding of ER stress in inflammatory bowel disease
      pathogenesis, it is now possible to develop novel therapies to improve ER protein
      folding homeostasis and target-specific UPR pathways in cells residing in the
      intestinal mucosa.

PMID- 25581828
TI  - Overview of venous thrombosis in inflammatory bowel disease.
AB  - Thrombosis in inflammatory bowel disease (IBD) is an increasingly noted
      extraintestinal manifestation with high morbidity and mortality. While
      controlling the activity of the disease with the appropriate therapy,
      thromboembolism prophylaxis should be applied to all patients. All common risk
      factors for thromboembolism are also valid for patients with IBD; however, it is
      clear that uncontrolled disease and hospitalization are major disease-specific
      risk factors for venous thromboembolism in patients with IBD. Pharmacological
      thromboprophylaxis with currently available anticoagulants does not increase the
      risk of further bleeding in patients with IBD with mild-to-moderate bleeding. In
      severe bleeding or with increased risk of further bleeding due to other comorbid
      conditions, thromboprophylaxy with mechanical methods should be the treatment
      option. Whether thrombosis is the cause or the result of intestinal inflammation
      remains to be elucidated, and other issues in the etiology, such as the role of
      intestinal flora in thrombosis pathogenesis, will be the subject of future
      studies. 

PMID- 25581826
TI  - Change in erythrocyte mean corpuscular volume during combination therapy with
      azathioprine and infliximab is associated with mucosal healing: a post hoc
      analysis from SONIC.
AB  - BACKGROUND: The adequacy of exposure of purine analogs as measured by 6
      thioguanine nucleotides concentrations in the setting of combination therapy
      remains poorly understood. The aim of this study was to investigate the
      relationship between the mean corpuscular volume (MCV) value (as a surrogate
      marker of 6-thioguanine nucleotides concentration) and Crohn's disease outcomes
      in the setting of combination therapy with infliximab. METHODS: The SONIC trial
      was a randomized controlled trial comparing infliximab to azathioprine and to
      infliximab plus azathioprine in 508 Crohn's disease patients. An increase of at
      least 7 femtoliter (fL) of the MCV (DeltaMCV) was used for statistical analysis.
      RESULTS: At week 26, the mean increase of MCV was similar among patients treated
      with azathioprine alone (mean of 7.9 fL) or in combination with infliximab (mean
      of 8.5 fL). In the azathioprine group, 63.6% of patients with DeltaMCV >7 were in
      steroid-free clinical remission at week 26 as compared with 33.3% of patients
      without DeltaMCV >7 (P = 0.0046). In the combination therapy group, DeltaMCV
      above 7 was associated with mucosal healing (75.0% for DeltaMCV >7 versus 47.1%
      for DeltaMCV <7, P = 0.0172) but not with steroid-free clinical remission.
      Patients with a DeltaMCV above 7 were more likely to have infliximab trough level
      above 3 MUg/mL at week 30 (68.4% versus 38.8% for DeltaMCV <7, P = 0.0032).
      CONCLUSIONS: These results suggest that DeltaMCV above 7 (which is a surrogate
      for a higher 6-thioguanine nucleotides concentration) leads to improved Crohn's
      disease outcomes, even when combined with infliximab. It also suggests the
      possibility that a lower azathioprine exposure might be less effective in
      combination therapy.

PMID- 25581829
TI  - Microbial DNA recognition by cGAS-STING and other sensors in dendritic cells in
      inflammatory bowel diseases.
AB  - Recognition of microbial nucleic acid initiates host immune defenses against
      pathogens. Impaired recognition of nucleic acid is involved in the pathogenesis
      of inflammatory bowel diseases. In contrast to the relatively well-established
      mechanism of microbial RNA sensing and associated signaling cascades, very little
      is known on how microbial DNA activates intracellular DNA sensors and controls
      the function of antigen-presenting cells (especially dendritic cells) to shape
      mucosal immune responses in intestine. In this review, we will introduce mucosal
      dendritic cell population, describe various putative DNA sensors, emphasize on
      newly identified cGAS-cGAMP-STING complex, and discuss how the detection of
      foreign DNA by mucosal dendritic cells activates innate and adaptive immune
      responses in intestine. Finally, we will identify certain inflammatory bowel
      disease-susceptibility genes that associate with impaired microbial DNA
      recognition in human. 

PMID- 25581830
TI  - Immune-mediated reactions to anti-tumor necrosis factors in inflammatory bowel
      disease.

PMID- 25581831
TI  - Hispanics and inflammatory bowel disease.
AB  - BACKGROUND: Historically, inflammatory bowel disease (IBD) was considered a
      disease, which predominately affects whites. As such, the majority of research in
      IBD has been conducted in this population. However, more research on this
      suggests that IBD affects other ethnic groups. Rapidly shifting demographics in
      the United States necessitates a better understanding of how IBD may affect
      Hispanics. We reviewed the current literature on IBD in Hispanics. METHODS: A
      PubMed search was conducted using keywords inflammatory bowel disease, Ulcerative
      Colitis, Crohn's disease, Hispanics, Latinos, ethnicity, to identify existing
      literature with a focus on adult populations. Non-English language articles were
      excluded. RESULTS: The existing data and literature on Hispanic patients with IBD
      remains sparse. Limited studies on prevalence suggest IBD may be more common in
      Hispanics in the United States compared with those in Latin America. Conflicting
      data exist as to whether Hispanics patients with IBD are more likely to have
      ulcerative colitis compared with Crohn's disease. One study explored difference
      in IBD between foreign-born and U.S.-born Hispanics and found that ulcerative
      colitis was more common only in foreign-born Hispanics, whereas within 1
      generation, U.S.-born Hispanics resemble their non-Hispanic white counterparts
      about development of Crohn's disease. Such a rapid change in the proportion of
      ulcerative colitis and Crohn's disease points strongly to environmental factors
      driving the change in proportion of disease subtypes. Additionally, a trend
      towards less use of biologic and immunomodulators in Hispanics was noted in
      several studies. CONCLUSIONS: Additional research is needed to better understand
      how diversity within the Hispanic population (U.S.-born and foreign-born) may be
      driving difference in disease manifestations. More investigations should focus on
      determining the cause of a potential disparity in the use of biologic and
      immunomodulators in Hispanics.

PMID- 25581834
TI  - Prevention and treatment of venous thromboembolism in patients with IBD: a trail
      still climbing.
AB  - Venous thromboembolism (VTE) represents one of the most common and life
      threatening extraintestinal complications of inflammatory bowel disease (IBD).
      Therefore, the prevention of VTE is essential and foremost involves the
      assessment of individual patient risk factors for VTE and, consequently, the
      correction of those risk factors that are modifiable. Mechanical and
      pharmacological prophylaxis are highly effective at preventing VTE in patients
      hospitalized for acute disease, and they are recommended by the leading
      guidelines for hospitalized patients with IBD. Unfortunately, several recent
      surveys reported that prophylaxis against VTE is still poorly implemented because
      of concerns about its safety and a lack of awareness of the magnitude of
      thrombotic risk in patients with IBD. Therefore, further efforts are required to
      increase the thromboprophylaxis rate in these patients to bridge the gap between
      the best care and standard care and, consequently, to avoid preventable VTE
      associated morbidity and mortality. This review provides insight on the critical
      points that persist on the prevention and treatment of VTE in patients with IBD. 

PMID- 25581832
TI  - Combinatorial effects of diet and genetics on inflammatory bowel disease
      pathogenesis.
AB  - Inflammatory bowel disease (IBD) encompasses a group of disorders affecting the
      gastrointestinal tract characterized by acute and chronic inflammation. These are
      complex and multifactorial disorders that arise in part from a genetic
      predisposition. However, the increasing incidence of IBD in developing countries
      suggests that environmental factors, such as diet, are also critical components
      of disease susceptibility. Evidence suggests that consumption of a Western diet,
      enriched with saturated fat, refined carbohydrates, and food additives, is
      associated with increased IBD risk. Dietary components, such as omega-6 fatty
      acids, long-chain fatty acids, protein, and digestible carbohydrates, may
      contribute to IBD pathogenesis through altering intestinal microbiota, increasing
      intestinal permeability, and promoting inflammation; whereas omega-3 fatty acids,
      medium chain triglycerides, and nondigestible carbohydrates improve these
      parameters and intestinal health. However, the limited amount of prospective
      studies, small sample sizes, and the heterogeneity of disease subtype result in
      inconsistencies between studies and difficulty in conclusively determining the
      specific effects of diet on intestinal homeostasis. There are no standard
      clinical dietary recommendations for patients with IBD. However, exclusionary
      diet interventions have shown some efficacy in relieving symptoms or inducing
      remission, suggesting more research is needed to fully understand how diet
      influences disease behavior or combines with other IBD risk factors to promote
      disease. This review focuses on the associations of various dietary components
      and IBD risk in clinical studies and genetically susceptible IBD models. 

PMID- 25581835
TI  - Inflammatory bowel disease: an emergent disease among Ethiopian Jews migrating to
      Israel.
AB  - BACKGROUND: The development and characteristics of inflammatory bowel disease
      (IBD) in Ethiopian Jewish immigrants to Israel were investigated. METHODS: A case
      control study was conducted in 7 tertiary care hospitals in Israel. Patients of
      Ethiopian origin with IBD >6 months were included. Time of disease onset after
      immigration and age at diagnosis were recorded. Randomly chosen patients with IBD
      of Ashkenazi Jewish origin served as controls. Demographics and clinical
      parameters were compared between the 2 cohorts. RESULTS: Thirty-two Ethiopian
      patients with IBD were compared with 33 Ashkenazi Jewish patients with IBD.
      Crohn's disease (CD) was more prevalent than ulcerative colitis (UC) in the
      Ethiopian group compared with the Ashkenazi group (94% versus 73%, P = 0.02). No
      Ethiopian-origin patient had a positive family history of IBD compared with 42%
      of Ashkenazi-origin patients (P < 0.001). Arthritis was more common in Ashkenazi
      than in Ethiopian patients (27% versus 3%, P < 0.01). One Ashkenazi patient with
      CD had upper gastrointestinal involvement compared with 7 (23%) in the Ethiopian
      group (P < 0.02). All other clinical measures were similar between the 2 cohorts.
      The Ethiopian group lived in Israel with a mean of 13 +/- 5 years, and 75% were
      born in Ethiopia. The shortest time between immigration and developing IBD was 8
      years (range, 8-26; median 16 yrs). No Ethiopian patient was diagnosed before
      immigration. CONCLUSIONS: Ethiopian Jews migrating to Israel are at risk of
      developing IBD. Larger cohorts are needed to determine the relative importance of
      environmental and genetic factors that cause IBD in these patients.

PMID- 25581833
TI  - Role of protein tyrosine phosphatases in regulating the immune system:
      implications for chronic intestinal inflammation.
AB  - Current hypothesis suggests that genetic, immunological, and bacterial factors
      contribute essentially to the pathogenesis of inflammatory bowel disease.
      Variations within the gene loci encoding protein tyrosine phosphatases (PTPs)
      have been associated with the onset of inflammatory bowel disease. PTPs modulate
      the activity of their substrates by dephosphorylation of tyrosine residues and
      are critical for the regulation of fundamental cellular signaling processes.
      Evidence emerges that expression levels of PTPN2, PTPN11, and PTPN22 are altered
      in actively inflamed intestinal tissue. PTPN2 seems to be critical for protecting
      intestinal epithelial barrier function, regulating innate and adaptive immune
      responses and finally for maintaining intestinal homeostasis. These observations
      have been confirmed in PTPN2 knockout mice in vivo. Those animals are clearly
      more susceptible to intestinal and systemic inflammation and feature alterations
      in innate and adaptive immune responses. PTPN22 controls inflammatory signaling
      in lymphocytes and mononuclear cells resulting in aberrant cytokine secretion
      pattern and autophagosome formation. PTPN22 deficiency in vivo results in more
      severe colitis demonstrating the relevance of PTPN22 for intestinal homeostasis
      in vivo. Of note, loss of PTPN22 promotes mitogen-activated protein kinase
      induced cytokine secretion but limits secretion of nuclear factor kappaB
      associated cytokines and autophagy in mononuclear cells. Loss of PTPN11 is also
      associated with increased colitis severity in vivo. In summary, dysfunction of
      those PTPs results in aberrant and uncontrolled immune responses that result in
      chronic inflammatory conditions. This way, it becomes more and more evident that
      dysfunction of PTPs displays an important factor in the pathogenesis of chronic
      intestinal inflammation, in particular inflammatory bowel disease.

PMID- 25581836
TI  - Features of acute liver congestion on gadoxetate disodium-enhanced MRI in a rat
      model: Role of organic anion-transporting polypeptide 1A1.
AB  - PURPOSE: To evaluate the features of hepatic congestion on gadoxetate disodium
      (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and the mechanisms
      responsible for the radiological findings in a rat model of partial liver
      congestion. MATERIALS AND METHODS: A conventional T1 -weighted spin-echo sequence
      of the liver was performed using a 1.5T magnetic resonance imager with an 80-mm
      magnetic aperture for animal studies. We induced regional congestion using
      partial left lateral hepatic vein ligation (n = 5) and evaluated the following in
      both congestive liver (CL) and noncongestive liver (non-CL): 1) chronological
      changes in the relative enhancement (RE) up to 60 minutes after Gd-EOB-DTPA
      administration, and 2) mRNA and protein expression of rat organic anion
      transporting protein 1a1 (Oatp1a1). RESULTS: The RE in the CL reached a small
      peak (18%) at 5 minutes, corresponding to approximately half of the value
      observed in the non-CL, then slowly decreased in a linear manner thereafter. The
      degree of RE in the CL was significantly lower than that in the non-CL for up to
      30 minutes (P < 0.05). An immunohistological examination showed that Oatp1a1
      protein expression was downregulated in the CL. The mRNA level of Oatp1a1 in the
      CL was significantly upregulated, compared with that in control rat liver (P =
      0.046), whereas no significant difference was observed between the CL and the non
      CL (P = 0.698). CONCLUSION: The reduced signal intensity in the CL on Gd-EOB-DTPA
      enhanced MRI could be explained by the decreased uptake of Gd-EOB-DTPA via
      Oatp1a1 protein in the congestive area.

PMID- 25581837
TI  - Health care providers' perspectives of providing culturally competent care in the
      NICU.
AB  - OBJECTIVE: To examine the experiences and perceptions of health care providers
      caring for new immigrant families in the neonatal intensive care unit (NICU).
      DESIGN: Qualitative design using grounded theory methodology. SETTING: Two
      tertiary-level NICUs of two large metropolitan hospitals in western Canada.
      PARTICIPANTS: Fifty eight (58) health care providers from multiple disciplines.
      METHODS: Health care providers were interviewed during seven focus groups. We
      recorded and transcribed focus group data. We analyzed transcripts via line-by
      line coding, categorization of codes, concept saturation, and theme generation
      assisted through NVIVO software. RESULTS: Health care providers identified the
      nuanced construct of fragile interactions that is embedded within care of the new
      immigrant family in the NICU. During crisis, decision making, differing norms and
      beliefs, and language and communication are barriers that affected the fragile
      nature of interactions. During transition home, fragile interactions were
      affected by unintentional stereotyping, limited time for intangible activities,
      and lack of intuitive perceptions of the needs of new immigrant families. Health
      care providers employed caring and culturally competent strategies to overcome
      the fragile nature of interactions. CONCLUSION: Within the premise of providing
      family-centered care is the concept of honoring cultural, ethnic, and
      socioeconomic diversity; it is imperative that culturally competent care be
      considered and implemented as a separate stand-alone aspect when caring for new
      immigrant families.

PMID- 25581838
TI  - Transition-metal-catalyzed pi-bond-assisted C - H bond functionalization: an
      emerging trend in organic synthesis.
AB  - Transition-metal-catalyzed C - H activation is considered to be an important tool
      in organic synthesis and has been accepted and widely used by chemists because it
      is straightforward, cost-effective, and environmentally friendly. A variety of
      functional groups have been used to direct metal complexes and achieve
      regioselective C - H activation. Most directing is achieved through the sigma
      bond coordination of functional groups to the metal catalyst, followed by ortho
      selective C - H bond cleavage. However, recent work has demonstrated that pi
      coordinating functional groups can also assist in guiding metal complexes for
      site-selective C - H bond activation. This emerging approach significantly
      expands the scope of C - H activation reactions in organic synthesis. Herein,
      recent developments in this field are summarized.

PMID- 25581839
TI  - PDZ Domain in the Engineering and Production of a Saporin Chimeric Toxin as a
      Tool for targeting Cancer Cells.
AB  - In this paper we have studied a PDZ protein domain as a possible tool for
      cellular targeting of the ribosome inactivating protein Saporin, exploiting the
      ability of PDZ domains to recognize and bind short peptide sequences located at
      the C-terminus of a cognate protein. We have focused our attention on the PDZ
      domain from hCASK (Human calcium/calmodulin-dependent serine protein kinase) that
      binds extracellular CD98 in epithelial cells, being this antigen recognized as a
      marker for several human tumors and particularly considered a negative prognostic
      marker for human glioblastoma. We produced recombinant fusions of one or two
      hCASK-PDZ domains with the ribosome inactivating protein Saporin and assayed them
      on two human glioblastoma cell lines (GL15 and U87). These constructs proved to
      be toxic, with increasing activity as a function of the number of PDZ domains,
      and induce cell death by apoptotic mechanisms in a dose-dependent and/or time
      dependent manner.

PMID- 25581841
TI  - Carotid stenting-why treating an artery may not treat the patient.

PMID- 25581842
TI  - Red-back spider bite to the tympanic membrane with 21 day follow up.

PMID- 25581840
TI  - Bedside diagnosis of dysphagia: a systematic review.
AB  - Dysphagia is associated with aspiration, pneumonia, and malnutrition, but remains
      challenging to identify at the bedside. A variety of exam protocols and maneuvers
      are commonly used, but the efficacy of these maneuvers is highly variable. We
      conducted a comprehensive search of 7 databases, including MEDLINE, Embase, and
      Scopus, from each database's earliest inception through June 9, 2014. Studies
      reporting diagnostic performance of a bedside examination maneuver compared to a
      reference gold standard (videofluoroscopic swallow study or flexible endoscopic
      evaluation of swallowing with sensory testing) were included for analysis. From
      each study, data were abstracted based on the type of diagnostic method and
      reference standard study population and inclusion/exclusion characteristics,
      design, and prediction of aspiration. The search strategy identified 38 articles
      meeting inclusion criteria. Overall, most bedside examinations lacked sufficient
      sensitivity to be used for screening purposes across all patient populations
      examined. Individual studies found dysphonia assessments, abnormal pharyngeal
      sensation assessments, dual axis accelerometry, and 1 description of water
      swallow testing to be sensitive tools, but none were reported as consistently
      sensitive. A preponderance of identified studies was in poststroke adults,
      limiting the generalizability of results. No bedside screening protocol has been
      shown to provide adequate predictive value for presence of aspiration. Several
      individual exam maneuvers demonstrated reasonable sensitivity, but
      reproducibility and consistency of these protocols was not established. More
      research is needed to design an optimal protocol for dysphagia detection.

PMID- 25581843
TI  - Chromodomain, Helicase and DNA-binding CHD1 protein, CHR5, are involved in
      establishing active chromatin state of seed maturation genes.
AB  - Chromatin modification and remodelling are the basis for epigenetic regulation of
      gene expression. LEAFY COTYLEDON 1 (LEC1), LEAFY COTYLEDON 2 (LEC2), ABSCISIC
      ACID-INSENSITIVE 3 (ABI3) and FUSCA3 (FUS3) are key regulators of embryo
      development and are repressed after seed maturation. The chromatin remodelling
      CHD3 protein PICKLE (PKL) is involved in the epigenetic silencing of the genes.
      However, the chromatin mechanism that establishes the active state of these genes
      during early embryo development is not clear. We show that the Arabidopsis CHD1
      related gene, CHR5, is activated during embryo development. Mutation of the gene
      reduced expression of LEC1, ABI3 and FUS3 in developing embryo and accumulation
      of seed storage proteins. Analysis of double mutants revealed an antagonistic
      function between CHR5 and PKL in embryo gene expression and seed storage protein
      accumulation, which likely acted on the promoter region of the genes. CHR5 was
      shown to be associated with the promoters of ABI3 and FUS3 and to be required to
      reduce nucleosome occupancy near the transcriptional start site. The results
      suggest that CHR5 is involved in establishing the active state of embryo
      regulatory genes by reducing nucleosomal barrier, which may be exploited to
      enhance seed protein production. 

PMID- 25581844
TI  - Immune response in the adipose tissue of lean mice infected with the protozoan
      parasite Neospora caninum.
AB  - The adipose tissue can make important contributions to immune function.
      Nevertheless, only a limited number of reports have investigated in lean hosts
      the immune response elicited in this tissue upon infection. Previous studies
      suggested that the intracellular protozoan Neospora caninum might affect adipose
      tissue physiology. Therefore, we investigated in mice challenged with this
      protozoan if immune cell populations within adipose tissue of different
      anatomical locations could be differently affected. Early in infection, parasites
      were detected in the adipose tissue and by 7 days of infection increased numbers
      of macrophages, regulatory T (Treg) cells and T-bet(+) cells were observed in
      gonadal, mesenteric, omental and subcutaneous adipose tissue. Increased
      expression of interferon-gamma was also detected in gonadal adipose tissue of
      infected mice. Two months after infection, parasite DNA was no longer detected in
      these tissues, but T helper type 1 (Th1) cell numbers remained above control
      levels in the infected mice. Moreover, the Th1/Treg cell ratio was higher than
      that of controls in the mesenteric and subcutaneous adipose tissue.
      Interestingly, chronically infected mice presented a marked increase of serum
      leptin, a molecule that plays a role in energy balance regulation as well as in
      promoting Th1-type immune responses. Altogether, we show that an apicomplexa
      parasitic infection influences immune cellular composition of adipose tissue
      throughout the body as well as adipokine production, still noticed at a chronic
      phase of infection when parasites were already cleared from that particular
      tissue. This strengthens the emerging view that infections can have long-term
      consequences for the physiology of adipose tissue.

PMID- 25581845
TI  - Ligand-controlled regiodivergent palladium-catalyzed decarboxylative allylation
      reaction to access alpha,alpha-difluoroketones.
AB  - alpha,alpha-Difluoroketones possess unique physicochemical properties that are
      useful for developing therapeutics and probes for chemical biology. To access the
      alpha-allyl-alpha,alpha-difluoroketone substructure, complementary palladium
      catalyzed decarboxylative allylation reactions were developed to provide linear
      and branched alpha-allyl-alpha,alpha-difluoroketones. For these orthogonal
      processes, the fluorination pattern of the substrate enabled the ligands to
      dictate the regioselectivity of the transformations. 

PMID- 25581848
TI  - Asymptomatic bacteriuria, what are you treating?

PMID- 25581846
TI  - Neurostimulation of the gastrointestinal tract: review of recent developments.
AB  - OBJECTIVE: Neurostimulation is one manifestation of neuromodulation of the
      gastrointestinal (GI) tract. This manuscript reviews the history of
      neurostimulation of the GI tract with emphasis on current methods of stimulation.
      MATERIALS AND METHODS: A review was completed of the current research on GI
      neurostimulation methods with an emphasis on their clinical applications.
      RESULTS: Upper GI disorders can be modulated with both temporary (placed
      endoscopically or surgically) or permanent (placed surgically) gastric electrical
      stimulation (GES) devices. The current GI neurostimulation of stomach (GES)
      devices have been used in both children and adults, and some patients have been
      followed in excess of 15 years with good long-term results. Similar GES devices
      also have been used for a variety of lower GI disorders, including constipation
      and fecal incontinence, for a number of years. CONCLUSIONS: GI neurostimulation,
      as a type of neuromodulation, has been demonstrated to function at several
      locations in the GI tract for a variety of disorders. The future of
      neurostimulation in the GI tract will likely be influenced by a better
      understanding of pathophysiology as well as the development of new techniques and
      devices for neuromodulation.

PMID- 25581847
TI  - Reconfigurable radio-frequency arbitrary waveforms synthesized in a silicon
      photonic chip.
AB  - Photonic methods of radio-frequency waveform generation and processing can
      provide performance advantages and flexibility over electronic methods due to the
      ultrawide bandwidth offered by the optical carriers. However, bulk optics
      implementations suffer from the lack of integration and slow reconfiguration
      speed. Here we propose an architecture of integrated photonic radio-frequency
      generation and processing and implement it on a silicon chip fabricated in a
      semiconductor manufacturing foundry. Our device can generate programmable radio
      frequency bursts or continuous waveforms with only the light source, electrical
      drives/controls and detectors being off-chip. It modulates an individual pulse in
      a radio-frequency burst within 4 ns, achieving a reconfiguration speed three
      orders of magnitude faster than thermal tuning. The on-chip optical delay
      elements offer an integrated approach to accurately manipulating individual radio
      frequency waveform features without constraints set by the speed and timing
      jitter of electronics, and should find applications ranging from high-speed
      wireless to defence electronics.

PMID- 25581849
TI  - Perforated jejunal diverticulum: a case report.

PMID- 25581850
TI  - Fructose-containing sugars do not raise blood pressure or uric acid at normal
      levels of human consumption.

PMID- 25581852
TI  - Towards an integrated understanding of the consequences of fungus domestication
      on the fungus-growing termite gut microbiota.
AB  - Approximately 30 million years ago (MYA), the subfamily of higher termites
      Macrotermitinae domesticated a fungus, Termitomyces, as the main plant decomposer
      and food source for the termite host. The origin of fungiculture shifted the
      composition of the termite gut microbiota, and some of the functional
      implications of this shift have recently been established. I review reports on
      the composition of the Macrotermitinae gut microbiota, evidence for a subfamily
      core gut microbiota, and the first insight into functional complementarity
      between fungal and gut symbionts. In addition, I argue that we need to explore
      the capacities of all members of the symbiotic communities, including better
      solidifying Termitomyces role(s) in order to understand putative complementary
      gut bacterial contributions. Approaches that integrate natural history and
      sequencing data to elucidate symbiont functions will be powerful, particularly if
      executed in comparative analyses across the well-established congruent termite
      fungus phylogenies. This will allow for testing if gut communities have evolved
      in parallel with their hosts, with implications for our general understanding of
      the evolution of gut symbiont communities with hosts. 

PMID- 25581851
TI  - Seizures, cysticercosis and rural-to-urban migration: the PERU MIGRANT study.
AB  - OBJECTIVES: To examine the prevalence of seizures, epilepsy and seropositivity to
      cysticercosis in rural villagers (cysticercosis-endemic setting), rural-to-urban
      migrants into a non-endemic urban shanty town and urban inhabitants of the same
      non-endemic shanty town. METHODS: Three Peruvian populations (n = 985) originally
      recruited into a study about chronic diseases and migration were studied. These
      groups included rural inhabitants from an endemic region (n = 200), long-term
      rural-to-urban migrants (n = 589) and individuals living in the same urban
      setting (n = 196). Seizure disorders were detected by a survey, and a neurologist
      examined positive respondents. Serum samples from 981/985 individuals were
      processed for cysticercosis antibodies on immunoblot. RESULTS: Epilepsy
      prevalence (per 1000 people) was 15.3 in the urban group, 35.6 in migrants and 25
      in rural inhabitants. A gradient in cysticercosis antibody seroprevalence was
      observed: urban 2%, migrant 13.5% and rural group 18% (P < 0.05). A similarly
      increasing pattern of higher seroprevalence was observed among migrants by age at
      migration. In rural villagers, there was strong evidence of an association
      between positive serology and having seizures (P = 0.011) but such an association
      was not observed in long-term migrants or in urban residents. In the entire study
      population, compared with seronegative participants, those with strong antibody
      reactions (>= 4 antibody bands) were more likely to have epilepsy (P < 0.001).
      CONCLUSIONS: It is not only international migration that affects cysticercosis
      endemicity; internal migration can also affect patterns of endemicity within an
      endemic country. The neurological consequences of cysticercosis infection likely
      outlast the antibody response for years after rural-to-urban migration.

PMID- 25581853
TI  - Climate warming and agricultural stressors interact to determine stream
      macroinvertebrate community dynamics.
AB  - Global climate change is likely to modify the ecological consequences of
      currently acting stressors, but potentially important interactions between
      climate warming and land-use related stressors remain largely unknown.
      Agriculture affects streams and rivers worldwide, including via nutrient
      enrichment and increased fine sediment input. We manipulated nutrients
      (simulating agricultural run-off) and deposited fine sediment (simulating
      agricultural erosion) (two levels each) and water temperature (eight levels, 0-6
      degrees C above ambient) simultaneously in 128 streamside mesocosms to determine
      the individual and combined effects of the three stressors on macroinvertebrate
      community dynamics (community composition and body size structure of benthic,
      drift and insect emergence assemblages). All three stressors had pervasive
      individual effects, but in combination often produced additive or antagonistic
      outcomes. Changes in benthic community composition showed a complex interplay
      among habitat quality (with or without sediment), resource availability (with or
      without nutrient enrichment) and the behavioural/physiological tendency to drift
      or emerge as temperature rose. The presence of sediment and raised temperature
      both resulted in a community of smaller organisms. Deposited fine sediment
      strongly increased the propensity to drift. Stressor effects were most prominent
      in the benthic assemblage, frequently reflected by opposite patterns in
      individuals quitting the benthos (in terms of their propensity to drift or
      emerge). Of particular importance is that community measures of stream health
      routinely used around the world (taxon richness, EPT richness and diversity) all
      showed complex three-way interactions, with either a consistently stronger
      temperature response or a reversal of its direction when one or both agricultural
      stressors were also in operation. The negative effects of added fine sediment,
      which were often stronger at raised temperatures, suggest that streams already
      impacted by high sediment loads may be further degraded under a warming climate.
      However, the degree to which this will occur may also depend on in-stream
      nutrient conditions. 

PMID- 25581854
TI  - Harnessing medically relevant metals onto water-soluble subphthalocyanines:
      towards bimodal imaging and theranostics.
AB  - Subphthalocyanine (SubPc), a putative fluorophore for optical imaging (OI), was
      conjugated to chelating ligands (DOTA, DTPA) affording water-soluble conjugates
      complexed with (non-radioactive) metals relevant to the following medical imaging
      techniques/therapies: MRI (Gd), PET (Cu, Ga), SPECT (In, Ga, Lu), RIT (Cu, Lu,
      Y), and NCT (Gd). Magneto-optical properties of ditopic gadolinium species (and
      optical properties of other metal containing species) were examined (brightness
      (epsilon * PhiF) and relaxivity R1) and fluorescence confocal/biphoton microscopy
      studies were conducted. 

PMID- 25581855
TI  - Sunflower seeds as eliciting agents of Compositae dermatitis.
AB  - BACKGROUND: Sunflowers may cause dermatitis because of allergenic sesquiterpene
      lactones (SLs). Contact sensitization to sunflower seeds has also been reported,
      but the allergens are unknown. OBJECTIVES: To analyse sunflower seeds for the
      presence of SLs and to assess the prevalence of sunflower sensitization in
      Compositae-allergic individuals. PATIENTS/MATERIALS/METHODS: Sunflower-sensitive
      patients were identified by aimed patch testing. A dichloromethane extract of
      whole sunflower seeds was analysed by liquid chromatography-mass spectrometry and
      high-performance liquid chromatography. RESULTS: The prevalence of sensitivity to
      sunflower in Compositae-allergic individuals was 56%. A solvent wash of whole
      sunflower seeds yielded an extract containing SLs, the principal component
      tentatively being identified as argophyllin A or B, other SLs being present in
      minute amounts. CONCLUSIONS: The concentration of SLs on the sunflower seeds is
      considered high enough to elicit dermatitis in sensitive persons, and it seems
      appropriate to warn Compositae-allergic subjects against handling sunflower
      seeds.

PMID- 25581856
TI  - Bioequivalence of ondansetron oral soluble film 8 mg (ZUPLENZ) and ondansetron
      orally disintegrating tablets 8 mg (ZOFRAN) in healthy adults.
AB  - Oral formulations of ondansetron are used to prevent nausea and vomiting
      associated with chemotherapy, radiotherapy, and surgery. An oral soluble film
      formulation of ondansetron (OND OSF) was developed using MonoSol Rx's proprietary
      PharmFilm technology and was formulated to dissolve rapidly on the tongue,
      without the need for water. This product provides an oral antiemetic treatment
      option for patients who experience difficulty swallowing. The purpose of this
      study was to compare the bioequivalence of OND OSF 8 mg (ZUPLENZ, Monosol Rx,
      Warren, NJ) with ondansetron orally disintegrating tablets (OND ODT) 8 mg
      (ZOFRAN, GlaxoSmithKline, Research Triangle Park). In 3 individual open-label,
      randomized studies, healthy adult subjects received a single dose of OND OSF 8 mg
      and a single dose of OND ODT 8 mg, under fasted conditions (study 1, n = 48), fed
      conditions (study 2, n = 48), and fasted with and without water (study 3, n =
      18). Each dosing period was followed by a 3- or 7-day washout period. Ondansetron
      pharmacokinetics were assessed predose to 24 hours postdose for the single 8-mg
      doses of OND OSF and OND ODT. All analyses were conducted on natural log
      transformed pharmacokinetic parameters for OND OSF and OND ODT. Under both fasted
      and fed conditions, the 90% confidence interval for the comparisons of OND OSF
      and OND ODT plasma ondansetron area under the curve from time 0 to the last
      measured concentration (AUC0-t), area under the concentration vs. time curve from
      time 0 to infinity (AUC0-infinity), and maximum plasma concentration (Cmax) were
      within the 80%-125% range, indicating bioequivalence between the formulations.
      With features designed to make it portable and easy to take, OND OSF 8 mg
      provides an alternative treatment option, particularly for patients with
      dysphagia and others who find it difficult to take oral tablets. 

PMID- 25581857
TI  - Sertraline-Induced Rhabdomyolysis: A Case Report and Literature Review.
AB  - The objective of this study is to report a case of sertraline-induced
      rhabdomyolysis in a female patient with a history of depression. A 25-year-old
      Hispanic woman with a history of depression reported to the emergency department
      (ED) with a chief complaint of muscle swelling and soreness and dark urine. The
      patient's creatine phosphokinase was 15,103 U/L. Despite treatment with IV normal
      saline, the patient's symptoms persisted and the creatine phosphokinase continued
      to rise to a peak of 16,778 U/L on day 2. The patient reported completing a
      strenuous, although routine, exercise the day before arriving at the ED, and her
      medication history was only significant for sertraline. Of note, 6 weeks before
      her visit to the ED, sertraline was increased from 100 mg daily to 150 mg daily.
      The patient's rhabdomyolysis was attributed to sertraline in conjunction with
      recent exercise. Selective serotonin reuptake inhibitor (SSRI)-induced
      rhabdomyolysis has been documented in 5 case reports. Similar to most reports,
      our patient presented with rhabdomyolysis in the presence of both SSRI use and
      exercise. Unlike the majority of previous reports, our patient was not taking
      other medications with documented association to rhabdomyolysis and had performed
      routine exercise before presenting with rhabdomyolysis. Although the mechanism of
      SSRI-induced rhabdomyolysis is not known, a theory posits that sertraline may
      have a role in muscle contraction and relaxation, leading to shorter time to
      contracture and longer time of contraction. The use of sertraline and other SSRIs
      may be associated with development of rhabdomyolysis, especially in the presence
      of strenuous exercise. 

PMID- 25581860
TI  - Peripheral nerve involvement in adult and pediatric patients with central nervous
      system inflammatory disease.

PMID- 25581861
TI  - Peripheral nerve involvement in adult and pediatric patients with central nervous
      system inflammatory disease--reply.

PMID- 25581862
TI  - Intracranial relationship between arterioles and venules size.

PMID- 25581863
TI  - Intracranial relationship between arterioles and venules size--reply.

PMID- 25581864
TI  - Laboratory testing for lyme neuroborreliosis.

PMID- 25581865
TI  - The impact of body weight on mortality after stroke: the controversy continues.

PMID- 25581867
TI  - The impact of body weight on mortality after stroke--reply.

PMID- 25581866
TI  - Laboratory testing for lyme neuroborreliosis--reply.

PMID- 25581871
TI  - Enantioselective determination of acaricide etoxazole in orange pulp, peel, and
      whole orange by chiral liquid chromatography with tandem mass spectrometry.
AB  - An efficient enantioselective method for the determination of etoxazole in orange
      pulp, peel, and whole orange was developed using liquid chromatography with
      tandem mass spectrometry. The enantioseparation was performed on a Chiralpak AD
      3R column at 30oC using acetonitrile with 0.1% formic acid solution (80:20, v/v)
      as the mobile phase in less than 5 min. Quantification was achieved using matrix
      matched standard calibration curves. The overall mean recoveries for two
      enantiomers from orange pulp and whole orange were 91.0-99.6% and the orange peel
      was 92.6-103.1%, with relative standard deviations of 0.8-5.4% intraday and 2.0
      4.8% interday at 1, 10, and 100 MUg/kg levels, and 1.3-5.2% intraday and 3.5-4.3%
      interday at 5, 50, and 500 MUg/kg levels, respectively. The limits of
      quantification for all enantiomers in three matrices did not exceed 5 MUg/kg.
      Moreover, the absolute configuration of etoxazole enantiomers had been determined
      by the combination of experimental and predicted electronic circular dichroism
      spectra, and the first eluted enantiomer was confirmed as (S)-etoxazole on a
      Chiralpak AD-3R column while (R)-etoxazole was first on three cellulose chiral
      columns. The application of the proposed method to real sample analysis suggests
      its potential use in enantioselective determination of etoxazole enantiomers in
      citrus. 

PMID- 25581872
TI  - Accumulation of glycogen in axotomized adult rat facial motoneurons.
AB  - This study biochemically determined glycogen content in the axotomized facial
      nucleus of adult rats up to 35 days postinsult. The amounts of glycogen in the
      transected facial nucleus were significantly increased at 5 days postinsult,
      peaked at 7 days postinsult, and declined to the control levels at 21-35 days
      postinsult. Immunohistochemical analysis with antiglycogen antibody revealed that
      the quantity of glycogen granules in the axotomized facial nucleus was greater
      than that in the control nucleus at 7 days postinjury. Dual staining methods with
      antiglycogen antibody and a motoneuron marker clarified that the glycogen was
      localized mainly in motoneurons. Immunoblotting and quantification analysis
      revealed that the ratio of inactive glycogen synthase (GS) to total GS was
      significantly decreased in the injured nucleus at about 1-3 days postinsult and
      significantly increased from 7 to 14 days postinsult, suggesting that glycogen is
      actively synthesized in the early period postinjury but suppressed after 7 days
      postinsult. The enhanced glycogen at about 5-7 days postinsult is suggested to be
      responsible for the decrease in inactive GS levels, and the decrease of glycogen
      after 7 days postinsult is considered to be caused by increased inactive GS
      levels and possibly the increase in active glycogen phosphorylase.

PMID- 25581874
TI  - Crystal structure of (4S)-aminoproline: conformational insight into a pH
      responsive proline derivative.
AB  - The crystal structure of a (4S)-configured ammoniumproline derivative is
      presented. The trifluoroacetic acid salt of the acetylated methylester of (4S)
      aminoproline (Ac-(4S)Amp-OMe) crystallized as the trans conformer with a C(4)
      endo ring pucker. The high-resolution structure shows typical parameters for a
      transannular H-bond and an n -> pi* interaction between the adjacent amide and
      ester groups. The structure corroborates previous findings of solution phase
      studies on the importance of these two interactions in acidic and neutral aqueous
      environments for the conformation of this pH-responsive proline derivative.

PMID- 25581875
TI  - Mycosis fungoides with psoriasiform lesions.

PMID- 25581873
TI  - The theory of RNA-mediated gene evolution.
AB  - Observations over the last decade suggest that some RNA transcripts, such as non
      coding RNAs, function in regulating the transcriptional and epigenetic state of
      gene expression. DNA methylation appears to be operative in non-coding RNA
      regulation of gene expression. Interestingly, methylated cytosines undergo
      deamination to remove the methylation, which if not properly repaired results in
      the methylated cytosine being recognized by the cell as a thymine. This
      observation suggests that the process of non-coding RNA-directed epigenetic
      targeting also has the potential to alter the genomic landscape of the cell by
      changing cytosines to thymines and ultimately influence the evolution of the
      cell. This proposed theory of "RNA-mediated gene evolution" might be one possible
      mechanism of action whereby RNA participates in the natural selective process to
      drive cellular and possibly organismal evolution. 

PMID- 25581876
TI  - Ultrasound-driven secondary self-assembly of amphiphilic beta-cyclodextrin
      dimers.
AB  - The controlled secondary self-assembly of amphiphilic molecules in solution is
      theoretically and practically significant in amphiphilic molecular applications.
      An amphiphilic beta-cyclodextrin (beta-CD) dimer, namely LA-(CD)2 , has been
      synthesized, wherein one lithocholic acid (LA) unit is hydrophobic and two beta
      CD units are hydrophilic. In an aqueous solution at room temperature, LA-(CD)2
      self-assembles into spherical micelles without ultrasonication. The primary
      micelles dissociates and then secondarily form self-assemblies with branched
      structures under ultrasonication. The branched aggregates revert to primary
      micelles at high temperature. The ultrasound-driven secondary self-assembly is
      confirmed by transmission electron microscopy, dynamic light scattering, (1) H
      NMR spectroscopy, and Cu(2+) -responsive experiments. Furthermore, 2D NOESY NMR
      and UV/Vis spectroscopy results indicate that the formation of the primary
      micelles is driven by hydrophilic-hydrophobic interactions, whereas host-guest
      interactions promote the formation of the secondary assemblies. Additionally,
      ultrasonication is shown to be able to effectively destroy the primary
      hydrophilic-hydrophobic balances while enhancing the host-guest interaction
      between the LA and beta-CD moieties at room temperature. 

PMID- 25581877
TI  - A 2013 European survey of clinical practice patterns in the management of Graves'
      disease.
AB  - OBJECTIVE: Management of Graves' disease (GD) in Europe was published in 1987.
      Aim of this survey was to provide an update on clinical practice in Europe, and
      to compare it with a 2011 American survey. DESIGN: Members of the European
      Thyroid Association (ETA) were asked to participate in a survey on management of
      GD, using the same questionnaire of a recent American survey. RESULTS: A total of
      147 ETA members participated. In addition to serum TSH and free T4 assays, most
      respondents would request TSH-receptor autoantibody (TRAb) measurement (85.6%)
      and thyroid ultrasound (70.6%) to confirm aetiology, while isotopic studies were
      selected by 37.7%. Antithyroid drug (ATD) therapy was the preferred first-line
      treatment (83.8%). Compared to the previous European survey, Europeans currently
      more frequently use TRAb measurement and thyroid ultrasound for diagnosis and
      evaluation, but first-line treatment remains ATDs in a similar percentage of
      respondents. Current clinical practice patterns differ from those in North
      America, where isotopic studies are more frequently used, and radioiodine (RAI)
      still is first-line treatment. When RAI treatment is selected in the presence of
      mild Graves' orbitopathy and/or associated risk factors for its
      occurrence/exacerbation, steroid prophylaxis is frequently used. The preferred
      ATD in pregnancy is propylthiouracil in the first trimester and methimazole in
      the second and third trimesters, similar to North America. CONCLUSIONS:
      Significant changes in clinical practice patterns in Europe were noted compared
      to the previous European survey, as well as persisting differences in diagnosis
      and therapy between Europe and North America.

PMID- 25581878
TI  - Antimicrobial Peptides Derived from Fusion Peptides of Influenza A Viruses, a
      Promising Approach to Designing Potent Antimicrobial Agents.
AB  - The emergence and dissemination of antibiotic-resistant bacterial pathogens have
      spurred the urgent need to develop novel antimicrobial agents with different mode
      of action. In this respect, we turned several fusogenic peptides (FPs) derived
      from the hemagglutinin glycoproteins (HAs) of IAV into potent antibacterials by
      replacing the negatively or neutrally charged residues of FPs with positively
      charged lysines. Their antibacterial activities were evaluated by testing the
      MICs against a panel of bacterial strains including S. aureus, S. mutans, P.
      aeruginosa, and E. coli. The results showed that peptides HA-FP-1, HA-FP-2-1, and
      HA-FP-3-1 were effective against both Gram-positive and Gram-negative bacteria
      with MICs ranging from 1.9 to 16.0 MUm, while the toxicities toward mammalian
      cells were low. In addition, the mode of action and the secondary structure of
      these peptides were also discussed. These data not only provide several potent
      peptides displaying promising potential in development as broad antimicrobial
      agents, but also present a useful strategy in designing new antimicrobial agents.

PMID- 25581879
TI  - Facile integration of multiple magnetite nanoparticles for theranostics combining
      efficient MRI and thermal therapy.
AB  - Multifunctional nanostructures with both diagnostic and therapeutic capabilities
      have attracted considerable attention in biomedical research because they can
      offer great advantages in disease management and prognosis. In this work, a
      facile way to transfer the hydrophobic iron oxide (IO) nanoparticles into aqueous
      media by employing carboxylic graphene oxide (GO-COOH) as the transferring agent
      has been reported. In this one-step process, IO nanoparticles adhere to GO-COOH
      and form water-dispersible clusters via hydrophobic interactions between the
      hydrophobic ligands of IO nanoparticles and the basal plane of GO-COOH. The
      multiple IO nanoparticles on GO-COOH sheets (IO/GO-COOH) present a significant
      increase in T2 contrast enhancement. Moreover, the IO/GO-COOH nanoclusters also
      display a high photothermal conversion efficiency and can effectively inhibit
      tumor growth through the photothermal effects. It is envisioned that such IO/GO
      COOH nanocomposites combining efficient MRI and photothermal therapy hold great
      promise in theranostic applications. 

PMID- 25581881
TI  - pn-Heterojunction effects of perylene tetracarboxylic diimide derivatives on
      pentacene field-effect transistor.
AB  - We investigated the heterojunction effects of perylene tetracarboxylic diimide
      (PTCDI) derivatives on the pentacene-based field-effect transistors (FETs). Three
      PTCDI derivatives with different substituents were deposited onto pentacene
      layers and served as charge transfer dopants. The deposited PTCDI layer, which
      had a nominal thickness of a few layers, formed discontinuous patches on the
      pentacene layers and dramatically enhanced the hole mobility in the pentacene
      FET. Among the three PTCDI molecules tested, the octyl-substituted PTCDI, PTCDI
      C8, provided the most efficient hole-doping characteristics (p-type) relative to
      the fluorophenyl-substituted PTCDIs, 4-FPEPTC and 2,4-FPEPTC. The organic
      heterojunction and doping characteristics were systematically investigated using
      atomic force microscopy, 2D grazing incidence X-ray diffraction studies, and
      ultraviolet photoelectron spectroscopy. PTCDI-C8, bearing octyl substituents,
      grew laterally on the pentacene layer (2D growth), whereas 2,4-FPEPTC, with
      fluorophenyl substituents, underwent 3D growth. The different growth modes
      resulted in different contact areas and relative orientations between the
      pentacene and PTCDI molecules, which significantly affected the doping efficiency
      of the deposited adlayer. The differences between the growth modes and the thin
      film microstructures in the different PTCDI patches were attributed to a mismatch
      between the surface energies of the patches and the underlying pentacene layer.
      The film-morphology-dependent doping effects observed here offer practical
      guidelines for achieving more effective charge transfer doping in thin-film
      transistors. 

PMID- 25581880
TI  - Fasting urinary calcium-to-creatinine and oxalate-to-creatinine ratios in dogs
      with calcium oxalate urolithiasis and breed-matched controls.
AB  - BACKGROUND: Hypercalciuria and hyperoxaluria are risk factors for calcium oxalate
      (CaOx) urolithiasis, but breed-specific reports of urinary metabolites and their
      relationship with stone status are lacking. OBJECTIVE: To compare urinary
      metabolites (calcium and oxalate) and blood ionized calcium (iCa) concentrations
      between CaOx stone formers and breed-matched stone-free controls for the
      Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds. ANIMALS: Forty-seven
      Miniature Schnauzers (23 cases and 24 controls), 27 Bichons Frise (14 cases and
      13 controls), and 15 Shih Tzus (7 cases and 8 controls). METHODS: Prospective
      study. Fasting spot urinary calcium-to-creatinine and oxalate-to-creatinine
      ratios (UCa/Cr and UOx/Cr, respectively) and blood iCa concentrations were
      measured and compared between cases and controls within and across breeds.
      Regression models were used to test the effect of patient and environmental
      factors on these variables. RESULTS: UCa/Cr was higher in cases than controls for
      each of the 3 breeds. In addition to stone status, being on a therapeutic food
      designed to prevent CaOx stone recurrence was associated with higher UCa/Cr.
      UOx/Cr did not differ between cases and controls for any of the breeds. Blood iCa
      was higher in cases than controls in the Miniature Schnauzer and Bichon Frise
      breeds and had a moderate correlation with UCa/Cr. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Hypercalciuria is associated with CaOx stone status in the Miniature
      Schnauzer, Bichon Frise, and Shih Tzu breeds. UOx/Cr did not correlate with stone
      status in these 3 breeds. These findings may influence breed-specific stone
      prevention recommendations.

PMID- 25581882
TI  - High-frequency jet ventilation for endolaryngotracheal surgery--chart review and
      procedure analysis from the surgeon's and the anaesthesiologist's point of view.
AB  - OBJECTIVE: High-frequency jet ventilation (HFJV) arose as a ventilation
      alternative in laryngotracheal surgery as it offers the surgeon a better overview
      and more space for microsurgical manipulations. On the contrary, anaesthesiologic
      monitoring is limited and (relative) contraindications exist. The aim of this
      study was to evaluate the procedure. Contraindications and limitations are
      discussed from the surgeon's and the anaesthesiologist's point of view, and
      relevant aspects of oncologic surgery are identified. DESIGN: Retrospective chart
      review and analysis of clinical experiences. SETTING: University Teaching
      hospital. PATIENTS AND MAIN OUTCOME MEASURES: Eighty adult patients (97 cases)
      treated at our institution between June 2012 and September 2013 were included.
      HFJV was performed using thin, subglottically placed catheters. The analysis
      focuses on complications and practical steps. RESULTS: Indications were benign
      (63%) and malignant pathologies (37%). The CO2 laser was used in 34 cases (35%).
      The mean operating time averaged 53 min (3-404 min) and the mean duration of
      anaesthesia was 81 min (16-438 min). Two thirds of the operated patients had a
      body mass index higher than 25 kg/m(2) . Eighty-four per cent were classified as
      ASA I and II according to the American Society of Anesthesiologists. All
      pathologies could well be exposed by the surgeon. Two reversible desaturations to
      70% were documented. In another case, emergency re-intubation was necessary as
      the saturation dropped below 50%. In 8 (8%) cases, elective re-intubation to
      conventional tubes was performed during the course of the operation as HFJV did
      not establish optimal oxygenation conditions. No severe intra-operative bleeding
      was observed. CONCLUSIONS: High-frequency jet ventilation represents a safe
      ventilation approach for laryngotracheal surgery in experienced hands. Due to the
      better overview, it offers a better orientation on anatomical structures and on
      the pathology. Special attention has to be laid on obesity, reflux and
      cardiopulmonary diseases. However, individual decisions can be made under
      consideration of all co-morbidities. A close pre- and intra-operative
      interdisciplinary work up is required.

PMID- 25581883
TI  - Oscillatory blood pressure response to the onset of cycling exercise in men: role
      of group III/IV muscle afferents.
AB  - NEW FINDINGS: What is the central question of this study? Neural feedback from
      group III/IV muscle afferents has a key role in regulation of cardiovascular
      responses to exercise. Blood pressure oscillates in the first seconds of dynamic
      exercise, but the contribution of muscle afferent feedback to this pattern is
      unclear. What is the main finding and its importance? We demonstrate that
      attenuation of group III/IV muscle afferent feedback by spinal fentanyl impairs
      the pressor response after 10 s of moderate leg cycling exercise, but this
      afferent feedback does not appear to be necessary for induction of the
      oscillatory pattern of blood pressure at the onset of exercise. We investigated
      whether attenuation of the central projections of group III/IV skeletal muscle
      afferents via lumbar intrathecal administration of the MU-opioid receptor agonist
      fentanyl affects the oscillatory blood pressure (BP) response to the onset of
      dynamic exercise. Eight healthy, recreationally active men (28 +/- 3 years old)
      performed 40 s of cycling at 80 W (60 r.p.m.) before (control) and after fentanyl
      administration, while heart rate, stroke volume, cardiac output, systolic, mean
      and diastolic BP and total vascular conductance were continuously monitored.
      Sytolic and mean BP responses to cycling included an initial increase (from 0 to
      3 s), followed by a transient decrease below resting levels (from 3 to 10 s) and
      then a sustained increase (>10 s). In the presence of fentanyl, systolic and mean
      BP responses closely matched those in control conditions in the first 10 s, but
      were blunted thereafter (P < 0.05). In contrast, fentanyl did not modify the
      heart rate, stroke volume, cardiac output, diastolic BP or total vascular
      conductance responses to 40 s of cycling (P > 0.05). These findings suggest that
      during moderate leg cycling exercise the muscle afferents contribute to the BP
      response after ~10 s, but that they do not appear to be implicated in the
      oscillation of BP at the onset of exercise.

PMID- 25581884
TI  - New double-layer design for 1-stage repair of orocutaneous and pharyngocutaneous
      fistulae in patients with postoperative irradiated head and neck cancer.
AB  - BACKGROUND: The development of a postoperative orocutaneous fistula (OCF) or
      pharyngocutaneous fistula (PCF) in the irradiated tissues of patients with head
      and neck cancer represents a high burden of morbidity for the patient. With high
      postoperative recurrence rates, these fistulae result in a reconstructive
      challenge for the plastic surgeon. In this study, we propose a new double-layer
      design to successfully repair these fistulae in a 1-stage reconstruction.
      METHODS: Twelve patients with an average age of 56 years (range, 45-67 years)
      were operated on between January 2006 and December 2012 using this double-layer
      single-stage technique. All patients had received postoperative radiotherapy
      after their initial reconstruction. A circumferential turnover flap was designed
      and raised from the skin surrounding the fistula to recreate inner lining using a
      tension-free, water-tight repair. No debridement of the fistula itself was
      performed. The second-layer of the reconstruction, which represents the outer
      lining, was achieved with either a local or a free flap. RESULTS: Fistula size
      ranged from 0.8 * 0.5 cm to 3 * 3.2 cm with a mean size of 2 cm(2) . The outer
      lining was achieved using a free flap in 5 cases and a local flap in 7 cases. All
      the flaps survived completely with no cases of postoperative infection, however,
      1 case was complicated by mandibular plate exposure necessitating its removal. No
      major complication or recurrence has yet been encountered in any of our patients
      with a mean follow-up of 28 months (range, 12-78 months). CONCLUSION: This 1
      stage double-layer design can provide a reliable and relatively straightforward
      means of repairing OCF and PCF in the irradiated tissues of patients with head
      and neck cancer. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E353-E359, 2016.

PMID- 25581885
TI  - A true bifurcational stenosis treated with a bioresorbable vascular scaffold and
      a drug-eluting metallic stent: Degradable meets durable.
AB  - The role of bioresorbable scaffolds (BRS) has mostly been investigated in simple
      coronary lesions. True bifurcational stenoses are one of the major challenges in
      interventional cardiology. We report here a successful case of a hybrid approach
      using a bioresorbable scaffold and a drug-eluting metallic stent to treat a true
      bifurcational lesion. Due to the degradable character of the BRS, only one
      metallic stent remains and thus the risk of restenosis can possibly be reduced.
      (c) 2015 Wiley Periodicals, Inc. 

PMID- 25581886
TI  - Hard gap in epitaxial semiconductor-superconductor nanowires.
AB  - Many present and future applications of superconductivity would benefit from
      electrostatic control of carrier density and tunnelling rates, the hallmark of
      semiconductor devices. One particularly exciting application is the realization
      of topological superconductivity as a basis for quantum information processing.
      Proposals in this direction based on the proximity effect in semiconductor
      nanowires are appealing because the key ingredients are currently in hand.
      However, previous instances of proximitized semiconductors show significant
      tunnelling conductance below the superconducting gap, suggesting a continuum of
      subgap states--a situation that nullifies topological protection. Here, we report
      a hard superconducting gap induced by the proximity effect in a semiconductor,
      using epitaxial InAs-Al semiconductor-superconductor nanowires. The hard gap,
      together with favourable material properties and gate-tunability, makes this new
      hybrid system attractive for a number of applications, as well as fundamental
      studies of mesoscopic superconductivity.

PMID- 25581887
TI  - Non-blinking quantum dot with a plasmonic nanoshell resonator.
AB  - Colloidal semiconductor quantum dots are fluorescent nanocrystals exhibiting
      exceptional optical properties, but their emission intensity strongly depends on
      their charging state and local environment. This leads to blinking at the single
      particle level or even complete fluorescence quenching, and limits the
      applications of quantum dots as fluorescent particles. Here, we show that a
      single quantum dot encapsulated in a silica shell coated with a continuous gold
      nanoshell provides a system with a stable and Poissonian emission at room
      temperature that is preserved regardless of drastic changes in the local
      environment. This novel hybrid quantum dot/silica/gold structure behaves as a
      plasmonic resonator with a strong Purcell factor, in very good agreement with
      simulations. The gold nanoshell also acts as a shield that protects the quantum
      dot fluorescence and enhances its resistance to high-power photoexcitation or
      high-energy electron beams. This plasmonic fluorescent resonator opens the way to
      a new family of plasmonic nanoemitters with robust optical properties. 

PMID- 25581888
TI  - Molecular bandgap engineering of bottom-up synthesized graphene nanoribbon
      heterojunctions.
AB  - Bandgap engineering is used to create semiconductor heterostructure devices that
      perform processes such as resonant tunnelling and solar energy conversion.
      However, the performance of such devices degrades as their size is reduced.
      Graphene-based molecular electronics has emerged as a candidate to enable high
      performance down to the single-molecule scale. Graphene nanoribbons, for example,
      can have widths of less than 2 nm and bandgaps that are tunable via their width
      and symmetry. It has been predicted that bandgap engineering within a single
      graphene nanoribbon may be achieved by varying the width of covalently bonded
      segments within the nanoribbon. Here, we demonstrate the bottom-up synthesis of
      such width-modulated armchair graphene nanoribbon heterostructures, obtained by
      fusing segments made from two different molecular building blocks. We study these
      heterojunctions at subnanometre length scales with scanning tunnelling microscopy
      and spectroscopy, and identify their spatially modulated electronic structure,
      demonstrating molecular-scale bandgap engineering, including type I
      heterojunction behaviour. First-principles calculations support these findings
      and provide insight into the microscopic electronic structure of bandgap
      engineered graphene nanoribbon heterojunctions. 

PMID- 25581896
TI  - Kinesin light chain-1 variant E disrupts axonal transport and Abeta generation in
      Alzheimer's disease (comment on DOI 10.1002/bies.201400131).

PMID- 25581889
TI  - Biodegradable chitosan nanoparticle coatings on titanium for the delivery of BMP
      2.
AB  - A simple method for the functionalization of a common implant material (Ti6Al4V)
      with biodegradable, drug loaded chitosan-tripolyphosphate (CS-TPP) nanoparticles
      is developed in order to enhance the osseointegration of endoprostheses after
      revision operations. The chitosan used has a tailored degree of acetylation which
      allows for a fast biodegradation by lysozyme. The degradability of chitosan is
      proven via viscometry. Characteristics and degradation of nanoparticles formed
      with TPP are analyzed using dynamic light scattering. The particle degradation
      via lysozyme displays a decrease in particle diameter of 40% after 4 days. Drug
      loading and release is investigated for the nanoparticles with bone morphogenetic
      protein 2 (BMP-2), using ELISA and the BRE luciferase test for quantification and
      bioactivity evaluation. Furthermore, nanoparticle coatings on titanium substrates
      are created via spray-coating and analyzed by ellipsometry, scanning electron
      microscopy and X-ray photoelectron spectroscopy. Drug loaded nanoparticle
      coatings with biologically active BMP-2 are obtained in vitro within this work.
      Additionally, an in vivo study in mice indicates the dose dependent induction of
      ectopic bone growth through CS-TPP-BMP-2 nanoparticles. These results show that
      biodegradable CS-TPP coatings can be utilized to present biologically active BMP
      2 on common implant materials like Ti6Al4V. 

PMID- 25581898
TI  - Preoperative apparent diffusion coefficient value of gastric cancer by diffusion
      weighted imaging: Correlations with postoperative TNM staging.
AB  - BACKGROUND: To determine if the apparent diffusion coefficient (ADC) values of
      gastric cancers on the preoperative diffusion weighted imaging (DWI) correlate
      with the postoperative TNMs of the lesions. METHODS: In a retrospective clinical
      study, seventy patients with gastric cancers were enrolled and each underwent a
      MRI before surgery. DWI was obtained with a single-shot, echo-planar imaging
      sequence in the axial plane (b values: 0 and 1000 s/mm(2) ). The mean and minimum
      ADC values of the gastric cancers were calculated and compared among various
      postoperative TNM staging. RESULTS: Both mean and minimum ADC values of the
      gastric cancers correlated with the postoperative T staging (r = -0.464, -0.476;
      both P < 0.001), N staging (r = -0.402, -0.397; P = 0.001, 0.002) and TNM staging
      (r = -0.446, -0.437; both P < 0.001). The areas under the receiver operating
      characteristic (ROC) curves for the differentiating lymph node metastasis were
      0.788 for the mean ADC values (P = 0.001) and 0.778 for the minimum ADC values (P
      = 0.001). CONCLUSION: The preoperative ADC values of gastric cancers can help to
      assess the postoperative TNM staging.

PMID- 25581897
TI  - Multimodal treatment with doxorubicin, cisplatin, and ifosfamide for the
      treatment of advanced or metastatic uterine leiomyosarcoma: a unicentric
      experience.
AB  - OBJECTIVE: Uterine leiomyosarcoma (ULMS) is a rare gynecologic malignancy
      characterized by a poor prognosis due to a high rate of local and metastatic
      recurrences. Chemotherapy with doxorubicin or ifosfamide or both is associated
      with a 10% to 30% objective response rate. We report a monocentric experience
      with doxorubicin, cisplatin, and ifosfamide (API) combination in the setting of
      multimodal treatment of advanced or metastatic ULMS. PATIENTS AND METHODS: This
      monocentric retrospective study included patients with metastatic or locally
      advanced ULMS with a physiological age younger than 65 years treated in first
      line with a multimodal aggressive approach with API chemotherapy. Treatment
      consisted of doxorubicin 50 mg/m2 d1, ifosfamide 3 g/m2 per day d1d2 plus mesna,
      cisplatin 75 mg/m2 d3, plus G-CSF; every 3 weeks up to 6 cycles. Surgery,
      radiation therapy, or radiofrequency ablation therapy of metastatic sites was
      associated whenever possible. RESULTS: Thirty-eight patients received API for
      metastatic or locally advanced ULMS. Median age was 51 years (40-64 years); 4
      (11%) patients were treated for a locally advanced disease and 34 (89%) for
      metastatic disease. Sixteen patients responded (4 complete responses+12 partial
      responses) among 33 evaluable patients (objective response rate, 48%); 8 and 9
      patients had, respectively, stable and progressive disease. Twelve patients had
      surgeries with 9 surgical complete responses and 3 surgical partial responses.
      Median progression-free and overall survival in the whole population were 9.8 and
      27 months, respectively. Main grade 3-4 toxicities in 38 patients were
      neutropenia (74%), thrombocytopenia (60%), anemia (55%), fatigue (18%), and
      vomiting (13%). Febrile neutropenia was observed in 37% of patients. CONCLUSIONS:
      Despite the toxicity observed, API is an effective treatment which compares
      favorably with other first-line therapies for patients with metastatic or
      advanced ULMS.

PMID- 25581899
TI  - Direct N-methylation reaction using DMSO as one-carbon bridge: convenient access
      to heterocycle-containing beta-amino ketones.
AB  - A novel oxidative C-S bond cleavage reaction of DMSO for dual C-C and C-N bond
      formation is described. A series of acetyl heteroarenes could be selectively
      converted into the corresponding beta-amino ketones, which are frequently found
      in biologically active compounds and pharmaceuticals. DMSO acted in this reaction
      not only as the solvent but also as a one-carbon bridge.

PMID- 25581901
TI  - Transient receptor potential vanilloid type 1 is vital for (-)-epigallocatechin-3
      gallate mediated activation of endothelial nitric oxide synthase.
AB  - SCOPE: Epigallocatechin-3-gallate (EGCG), the most abundant catechin of green
      tea, has beneficial effects on physiological functions of endothelial cells
      (ECs), yet the detailed mechanisms are not fully understood. In this study, we
      investigated the role of transient receptor potential vanilloid type 1 (TRPV1), a
      ligand-gated nonselective calcium channel, in EGCG-mediated endothelial nitric
      oxide (NO) synthase (eNOS) activation and angiogenesis. METHODS AND RESULTS: In
      ECs, treatment with EGCG time-dependently increased the intracellular level of
      Ca(2+) . Removal of extracellular calcium (Ca(2+) ) by EGTA or EDTA or inhibition
      of TRPV1 by capsazepine or SB366791 abrogated EGCG-increased intracellular Ca(2+)
      level in ECs or TRPV1-transfected HEK293 cells. Additionally, EGCG increased the
      phsophorylation of eNOS at Ser635 and Ser1179, Akt at Ser473, calmodulin
      dependent protein kinase II (CaMKII) at Thr286 and AMP-activated protein kinase
      (AMPK) at Thr172, all abolished by the TRPV1 antagonist capsazepine. EGCG-induced
      NO production was diminished by pretreatment with LY294002 (an Akt inhibitor),
      KN62 (a CaMKII inhibitor), and compound C (an AMPK inhibitor). Moreover, blocking
      TRPV1 activation prevented EGCG-induced EC proliferation, migration, and tube
      formation, as well as angiogenesis in Matrigel plugs in mice. CONCLUSION: EGCG
      may trigger activation of TRPV1-Ca(2+) signaling, which leads to phosphorylation
      of Akt, AMPK, and CaMKII; eNOS activation; NO production; and, ultimately,
      angiogenesis in ECs.

PMID- 25581900
TI  - Pyrosequencing for accurate imprinted allele expression analysis.
AB  - Genomic imprinting is an epigenetic mechanism that restricts gene expression to
      one inherited allele. Improper maintenance of imprinting has been implicated in a
      number of human diseases and developmental syndromes. Assays are needed that can
      quantify the contribution of each paternal allele to a gene expression profile.
      We have developed a rapid, sensitive quantitative assay for the measurement of
      individual allelic ratios termed Pyrosequencing for Imprinted Expression (PIE).
      Advantages of PIE over other approaches include shorter experimental time,
      decreased labor, avoiding the need for restriction endonuclease enzymes at
      polymorphic sites, and prevent heteroduplex formation which is problematic in
      quantitative PCR-based methods. We demonstrate the improved sensitivity of PIE
      including the ability to detect differences in allelic expression down to 1%. The
      assay is capable of measuring genomic heterozygosity as well as imprinting in a
      single run. PIE is applied to determine the status of Insulin-like Growth Factor
      2 (IGF2) imprinting in human and mouse tissues.

PMID- 25581902
TI  - Dipeptidyl peptidase-4 inhibitors and the risk of community-acquired pneumonia in
      patients with type 2 diabetes.
AB  - AIMS: To determine whether the use of dipeptidyl peptidase-4 (DPP-4) inhibitors
      is associated with an increased risk of community-acquired pneumonia. METHODS:
      The UK Clinical Practice Research Datalink and the Hospital Episodes Statistics
      database were used to conduct a nested case-control analysis within a cohort of
      new users of antidiabetic drugs between 2007 and 2012. Incident cases of
      hospitalization for community-acquired pneumonia were matched with up to 20
      controls on age, duration of treated diabetes, calendar year and duration of
      follow-up. Conditional logistic regression models were used to estimate the odds
      ratios (ORs) and 95% confidence intervals (CIs) for hospitalization for community
      acquired pneumonia associated with current use of DPP-4 inhibitors compared with
      current use of two or more oral antidiabetic drugs. RESULTS: The cohort included
      49,653 patients, of whom 562 were hospitalized for community-acquired pneumonia
      during follow-up (incidence rate 5.2/1000 person-years). Compared with current
      use of two or more oral antidiabetic drugs, current use of DPP-4 inhibitors was
      not associated with an increased risk of hospitalized community-acquired
      pneumonia overall (adjusted OR 0.80, 95% CI 0.50-1.29) or according to duration
      of use (p for trend = 0.57). CONCLUSIONS: The use of DPP-4 inhibitors was not
      associated with an increased risk of hospitalization for community-acquired
      pneumonia. Additional research is needed to assess the association between these
      drugs and other serious infections.

PMID- 25581903
TI  - Indolo-phakellins as beta5-specific noncovalent proteasome inhibitors.
AB  - The proteasome represents an invaluable target for the treatment of cancer and
      autoimmune disorders. The application of proteasome inhibitors, however, remains
      limited to blood cancers because their reactive headgroups and peptidic scaffolds
      convey unfavorable pharmacodynamic properties. Thus, the discovery of more drug
      like lead structures is indispensable. In this study, we present the first
      structure of the proteasome in complex with an indolo-phakellin that exhibits a
      unique noncovalent binding mode unparalleled by all hitherto reported inhibitors.
      The natural product inspired pentacyclic alkaloid binds solely and specificially
      into the spacious S3 subpocket of the proteasomal beta5 substrate binding
      channel, gaining major stabilization through halogen bonding with the protein
      backbone. The presented compound provides an ideal scaffold for the structure
      based design of subunit-specific nonpeptidic proteasome-blockers. 

PMID- 25581905
TI  - Twelve-dose drug regimen now also an option for preventing tuberculosis in
      children and adolescents.

PMID- 25581904
TI  - Large interdomain rearrangement triggered by suppression of micro- to millisecond
      dynamics in bacterial Enzyme I.
AB  - Enzyme I (EI), the first component of the bacterial phosphotransfer signal
      transduction system, undergoes one of the largest substrate-induced interdomain
      rearrangements documented to date. Here we characterize the perturbations
      generated by two small molecules, the natural substrate phosphoenolpyruvate and
      the inhibitor alpha-ketoglutarate, on the structure and dynamics of EI using NMR,
      small-angle X-ray scattering and biochemical techniques. The results indicate
      unambiguously that the open-to-closed conformational switch of EI is triggered by
      complete suppression of micro- to millisecond dynamics within the C-terminal
      domain of EI. Indeed, we show that a ligand-induced transition from a dynamic to
      a more rigid conformational state of the C-terminal domain stabilizes the
      interface between the N- and C-terminal domains observed in the structure of the
      closed state, thereby promoting the resulting conformational switch and
      autophosphorylation of EI. The mechanisms described here may be common to several
      other multidomain proteins and allosteric systems. 

PMID- 25581906
TI  - Enzymatic resolution of alpha-methyleneparaconic acids and evaluation of their
      biological activity.
AB  - Both enantiomers of three biologically relevant paraconic acids-MB-3,
      methylenolactocin, and C75-were obtained with enantioselectivities up to 99% by
      kinetic enzymatic resolutions. Good enantiomeric excesses were obtained for MB-3
      and methylenolactocin, using alpha-chymotrypsin and aminoacylase as
      enantiocomplementary enzymes, while C75 was resolved with aminoacylase. They all
      were evaluated for their antiproliferative, antibacterial, and antifungal
      activities, showing weak effects and practically no difference between
      enantiomers in each case. At high concentrations (16-64 ug/mL), (-)- C75 acted as
      an antimicrobial agent against Gram-positive bacteria.

PMID- 25581907
TI  - Four linear Cu(II)3 subunit-based coordination polymers with various inter
      subunit connections, spin ground-states and intra-/inter-subunit magnetic
      couplings.
AB  - Four new 4-amino-1,2,4-triazole (atr)-based coordination polymers,
      {[Cu2(atr)(H2O)(MU-OH)2(pa)].H2O}n (), {[Cu3(atr)2(H2O)2(MU-OH)2(npa)2].2H2O}n
      (), {[Cu3(atr)5(dca)(MU-OH)(ClO4)2](ClO4)2}n () and {[Cu3(atr)2(H2O)(MU3-OH)(MU
      OH)2(spa)].1.5H2O}n () (pa(2-) = phthalate, npa(2-) = 3-nitrophthalate, dca(-) =
      dicyanamide and spa(3-) = 4-sulfophthalate), were successfully obtained by
      varying the carboxylate- and cyanide-modified magnetic bridges. Structural
      determinations reveal that the former three samples are bent one-dimensional
      chains constructed from linear Cu(II)3 subunits and different inter-subunit
      connections. In , linear {Cu3(MU-N1,N2-atr)2(MU-OH)2}(4+) and {Cu3(MU-COO)2(MU
      OH)2}(4+) subunits are alternately connected in a sharing-vertex manner to give a
      ferrimagnetic S = 1/2 spin ground-state. The linear {Cu3(MU-N1,N2-atr)2(MU
      OH)2}(4+) building block of is repeatedly bridged by pairs of single-atom
      bridging carboxylate groups of the npa(2-) ligand leading to a paramagnetic S =
      1/2 spin ground-state. By contrast, each linear {Cu3(MU-N1,N2-atr)4}(6+) core in
      is periodically propagated by four-fold heterobridges (MU-OH(-), MU-ClO4(-), MU
      N1,N2-atr and MU-dca(-)) to generate an overall diamagnetic S = 0 spin ground
      state. Complex is a three-dimensional pillared-layer framework composed of linear
      {Cu3(MU-N1,N2-atr)2(MU-OH)2}(4+)-based layers and ditopic spa(3-) connectors,
      which exhibits a ferrimagnetic S = 1/2 spin ground-state and a metamagnetic
      transition resulting from the competition between the weak interchain/interlayer
      antiferromagnetic interaction and the enhanced external magnetic field. In
      addition, different intra- and inter-subunit magnetic strengths are observed in
      with the coupling constants 182 < -Jintra < 43 and -127 < Jinter < 51.2 cm(-1).
      These interesting magnetostructural results are significant and helpful for the
      cyclic polyazolate-based magnetic materials. 

PMID- 25581908
TI  - Endogenous pain modulation: from humans to animals and back.

PMID- 25581909
TI  - Using next-generation RNA sequencing to examine ischemic changes induced by cold
      blood cardioplegia on the human left ventricular myocardium transcriptome.
AB  - BACKGROUND: The exact mechanisms that underlie the pathological processes of
      myocardial ischemia in humans are unclear. Cardiopulmonary bypass with
      cardioplegic arrest allows the authors to examine the whole transcriptional
      profile of human left ventricular myocardium at baseline and after exposure to
      cold cardioplegia-induced ischemia as a human ischemia model. METHODS: The
      authors obtained biopsies from 45 patients undergoing aortic valve replacement
      surgery at baseline and after an average of 79 min of cold cardioplegic arrest.
      Samples were RNA sequenced and analyzed with the Partek Genomics Suite (Partek
      Inc., St. Louis, MO) for differential expression. Ingenuity Pathway Analysis
      (Ingenuity Systems, Redwood City, CA) and Biobase ExPlain (Biobase GmbH,
      Wolfenbuettel, Germany) systems were used for functional and pathway analyses.
      RESULTS: Of the 4,098 genes with a mean expression value greater than 5, 90% were
      down-regulated and 9.1% were up-regulated. Of those, 1,241 were significantly
      differentially expressed. Gene ontology analysis revealed significant down
      regulation in immune inflammatory response and complement activation categories
      and highly consistent was the down-regulation of intelectin 1, proteoglycan, and
      secretory leukocyte peptidase inhibitor. Up-regulated genes of interest were FBJ
      murine osteosarcoma viral oncogene homolog and the hemoglobin genes hemoglobin
      alpha1 (HBA1) and hemoglobin beta. In addition, analysis of transcription factor
      binding sites revealed interesting targets in factors regulating reactive oxygen
      species production, apoptosis, immunity, cytokine production, and inflammatory
      response. CONCLUSIONS: The authors have shown that the human left ventricle
      exhibits significant changes in gene expression in response to cold cardioplegia
      induced ischemia during cardiopulmonary bypass, which provides great insight into
      the pathophysiology of ventricular ischemia, and thus, may help guide efforts to
      reduce myocardial damage during surgery.

PMID- 25581911
TI  - Skin reaction and regeneration after single sodium lauryl sulfate exposure
      stratified by filaggrin genotype and atopic dermatitis phenotype.
AB  - BACKGROUND: Filaggrin is key for the integrity of the stratum corneum. Mutations
      in the filaggrin gene (FLGnull) play a prominent role in atopic dermatitis (AD)
      pathogenesis. People with AD have increased susceptibility to irritants. However,
      little is known about the effect of filaggrin genotype and AD phenotype on
      irritant response and skin regeneration. OBJECTIVES: To investigate the role of
      FLGnull and AD groups for skin reaction and recovery after sodium lauryl sulfate
      (SLS) irritation. METHODS: This is a case-control study comprising 67 subjects,
      including healthy controls and patients with and without FLGnull and AD.
      Reactivity to different doses of SLS at 24, 48, 72 and 145 h after SLS
      application was measured by transepidermal water loss (TEWL) and laser Doppler
      flowmetry (LDF). Reactivity was assessed univariately and by pattern analysis.
      RESULTS: All patient groups showed a higher degree of skin-barrier disruption and
      inflammation than did controls in response to SLS. Assessing reactivity by the
      delta value of the area under the curve for both TEWL and LDF showed significant
      differences between healthy controls and those with the AD phenotype,
      irrespective of filaggrin mutation. The poorest regeneration was among those with
      the AD phenotype. The two AD phenotype groups were separated by multivariate
      technique, due to earlier inflammatory reactivity among subjects with FLGnullplus
      AD compared with the AD phenotype alone. CONCLUSIONS: Both skin reaction and
      regeneration were significantly different between the patient population and the
      healthy controls. Additionally, response severity and regeneration depended more
      on AD phenotype than on filaggrin genotype, whereas the response was more rapid
      among the FLGnullplus AD individuals.

PMID- 25581912
TI  - The indications and efficacy of conventional chemotherapy in primary and
      recurrent sarcoma.
AB  - Conventional chemotherapy can have a favorable impact on the natural history of
      disease for selected patients with primary high-risk bone and soft-tissue
      sarcomas. In particular, multidrug regimens are integral to the care of patients
      with the most aggressive histologies, including Ewing sarcoma, osteosarcoma, and
      non-pleomorphic rhabdomyosarcoma. Appropriately selected patients with high-risk,
      clinically localized soft-tissue sarcomas may also benefit from histology
      tailored adjuvant or neoadjuvant therapy. For patients with recurrent disease,
      conventional chemotherapy is frequently the most appropriate first-line therapy;
      active drugs are discussed at length. Several new promising cytotoxic
      chemotherapeutic agents are currently under development, including aldoxorubicin,
      TH-302, and trabectedin.

PMID- 25581910
TI  - Individual differences in acute pain-induced endogenous analgesia predict time to
      resolution of postoperative pain in the rat.
AB  - BACKGROUND: Chronic postsurgical pain, a significant public health problem,
      occurs in 10 to 50% of patients undergoing major surgery. Acute pain induces
      endogenous analgesia termed conditioned pain modulation (CPM), and the strength
      of CPM preoperatively predicts the likelihood of chronic postsurgical pain. The
      relation between CPM and recovery from surgery has not been examined in
      preclinical models. METHODS: CPM was assessed in individual rats and correlated
      with each animal's time course of recovery of hypersensitivity after partial
      spinal nerve ligation. The role of descending noradrenergic pathways in the
      spinal cord to mechanisms of CPM and recovery was tested using idazoxan to block
      noradrenergic receptors or antidopamine beta-hydroxylase-conjugated saporin to
      ablate these pathways. Behavioral hypersensitivity, static weight bearing, and
      spinal glial activation were measured after partial spinal nerve ligation.
      RESULTS: The strength of CPM varied over two-fold between individuals and was
      directly correlated with the slope of recovery from hypersensitivity after
      surgery (P < 0.0001; r = 0.660). CPM induced the release of norepinephrine in the
      spinal cord and was partially blocked by intrathecal idazoxan or dopamine beta
      hydroxylase-saporin. Dopamine beta-hydroxylase-saporin also slowed recovery and
      enhanced spinal glial activation after partial spinal nerve ligation surgery.
      Ongoing activation of these pathways was critical to sustained recovery because
      intrathecal dopamine beta-hydroxylase-saporin given 7 weeks after recovery
      reinstituted hypersensitivity, while having no effect in animals without previous
      surgery. CONCLUSION: Collectively, these studies provide a clear back-translation
      from clinical observations of CPM and chronic postsurgical pain and suggest that
      the ability to engage ongoing descending endogenous noradrenergic signaling may
      be critical in determining time course of recovery from hypersensitivity after
      surgery.

PMID- 25581913
TI  - Natural history of excessive daytime sleepiness: role of obesity, weight loss,
      depression, and sleep propensity.
AB  - STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is highly prevalent in the
      general population and is associated with occupational and public safety hazards.
      However, no study has examined the clinical and polysomnographic (PSG) predictors
      of the natural history of EDS. DESIGN: Representative longitudinal study.
      SETTING: Sleep laboratory. PARTICIPANTS: From a random, general population sample
      of 1,741 individuals of the Penn State Adult Cohort, 1,395 were followed up after
      7.5 years. MEASUREMENTS AND RESULTS: Full medical evaluation and 1-night PSG at
      baseline and standardized telephone interview at follow-up. The incidence of EDS
      was 8.2%, while its persistence and remission were 38% and 62%, respectively.
      Obesity and weight gain were associated with the incidence and persistence of
      EDS, while weight loss was associated with its remission. Significant
      interactions between depression and PSG parameters on incident EDS showed that,
      in depressed individuals, incident EDS was associated with sleep disturbances,
      while in non-depressed individuals, incident EDS was associated with increased
      physiologic sleep propensity. Diabetes, allergy/ asthma, anemia, and sleep
      complaints also predicted the natural history of EDS. CONCLUSIONS: Obesity, a
      disorder of epidemic proportions, is a major risk factor for the incidence and
      chronicity of EDS, while weight loss is associated with its remission.
      Interestingly, objective sleep disturbances predict incident EDS in depressed
      individuals, whereas physiologic sleep propensity predicts incident EDS in those
      without depression. Weight management and treatment of depression and sleep
      disorders should be part of our public health policies.

PMID- 25581914
TI  - eAMI: a qualitative quantification of periodic breathing based on amplitude of
      oscillations.
AB  - STUDY OBJECTIVES: Periodic breathing is sleep disordered breathing characterized
      by instability in the respiratory pattern that exhibits an oscillatory behavior.
      Periodic breathing is associated with increased mortality, and it is observed in
      a variety of situations, such as acute hypoxia, chronic heart failure, and damage
      to respiratory centers. The standard quantification for the diagnosis of sleep
      related breathing disorders is the apnea-hypopnea index (AHI), which measures the
      proportion of apneic/ hypopneic events during polysomnography. Determining the
      AHI is labor-intensive and requires the simultaneous recording of airflow and
      oxygen saturation. In this paper, we propose an automated, simple, and novel
      methodology for the detection and qualification of periodic breathing: the
      estimated amplitude modulation index (eAMI). PATIENTS OR PARTICIPANTS: Antarctic
      Cohort (3800 meters): 13 normal individuals. Sleep Clinic Cohort: 39 different
      patients suffering from diverse sleep-related pathologies. MEASUREMENTS AND
      RESULTS: When tested in a population with high levels of periodic breathing
      (Antarctic Cohort), eAMI was closely correlated with AHI (r = 0.95, P < 0.001).
      When tested in the clinical setting, the proposed method was able to detect
      portions of the signal in which subclinical periodic breathing was validated by
      an expert (n = 93; accuracy = 0.85). Average eAMI was also correlated with the
      loop gain for the combined clinical and Antarctica cohorts (r = 0.58, P < 0.001).
      CONCLUSIONS: In terms of quantification and temporal resolution, the eAMI is able
      to estimate the strength of periodic breathing and the underlying loop gain at
      any given time within a record. The impaired prognosis associated with periodic
      breathing makes its automated detection and early diagnosis of clinical
      relevance.

PMID- 25581915
TI  - Regulation of Sleep by Insulin-like Peptide System in Drosophila melanogaster.
AB  - STUDY OBJECTIVES: Most organisms have behavioral and physiological circadian
      rhythms, which are controlled by an endogenous clock. Although genetic analysis
      has revealed the intracellular mechanism of the circadian clock, the manner in
      which this clock communicates its temporal information to produce systemic
      regulation is still largely unknown. DESIGN: Sleep behavior was measured using
      the Drosophila Activity Monitoring System (DAMS) monitor under a 12 h light:12 h
      dark cycle and constant darkness (DD), and 5 min without recorded activity were
      defined as a bout of sleep. RESULTS: Here we show that Drosophila insulin-like
      peptides (DILPs) and their receptor (DInR) regulate sleep behavior. All mutants
      of the seven dilps and the mutant of their receptor exhibit decreases of total
      sleep except dilp4 mutants, whereas upregulation of DILP and DInR in the nervous
      system led to increased sleep. Histological analysis identified four previously
      unidentified neurons expressing DILP: D1, P1, L1, and L2, of which L1 and L2
      belong to the LNd and LNv clock neurons that separately regulate different times
      of sleep. In addition, dilp2 levels significantly decrease when flies were
      fasted, which is consistent with a previous report that starvation inhibits
      sleep, further indicating that the dilp system is involved in sleep regulation.
      CONCLUSION: Taken together, the results indicate that the Drosophila insulin-like
      peptide system is a crucial regulator of sleep.

PMID- 25581916
TI  - Correlates and Escitalopram Treatment Effects on Sleep Disturbance in Patients
      with Acute Coronary Syndrome: K-DEPACS and EsDEPACS.
AB  - STUDY OBJECTIVES: To investigate the correlates of sleep disturbance and to
      assess escitalopram treatment effects of depression on sleep disturbance in
      patients with acute coronary syndrome (ACS). DESIGN: A cross-sectional study in
      patients with ACS within 2 w post-ACS, and a 24-w double-blind controlled trial
      of escitalopram against placebo for patients with ACS who have comorbid
      depressive disorders. SETTING: A university hospital in South Korea.
      PARTICIPANTS: There were 1,152 patients with ACS who were consecutively
      recruited. Of 446 patients with comorbid depressive disorders, 300 were
      randomized to the trial. MEASUREMENTS AND RESULTS: Sleep disturbance was
      evaluated by the Leeds Sleep Evaluation Questionnaire. Demographic and clinical
      characteristics were assessed, including cardiovascular risk factors, current
      cardiac status, and depressive symptoms. Depressive symptoms were most strongly
      and consistently associated with sleep disturbance. In addition, older age,
      female sex, hypertension, and more severe ACS status were associated with certain
      aspects of sleep disturbance. Escitalopram was significantly superior to placebo
      for improving sleep disturbance over the 24-w treatment period. These effects
      were substantially explained by improvement in depressive symptoms. CONCLUSIONS:
      Depression screening is indicated in patients with acute coronary syndrome with
      sleep disturbance. Successful treatment of depression has beneficial effects on
      sleep outcomes in these patients. CLINICAL TRIALS INFORMATION: ClinicalTrial.gov
      identifier for the 24-w drug trial, NCT00419471.

PMID- 25581917
TI  - Arousal Responses during Overnight Polysomnography and their Reproducibility in
      Healthy Young Adults.
AB  - STUDY OBJECTIVES: Arousal intensity and heart rate (HR) response to arousal
      during polysomnography (PSG) vary considerably between patients with sleep
      disorders. Our objective was to determine the range of these arousal
      characteristics in healthy young adults and whether they are consistent on
      repeated testing. DESIGN: Post hoc analysis of 56 preexisting PSG files recorded
      from 28 healthy adults on 2 consecutive nights. SETTING: Academic medical center
      and Research and Development Laboratory (YRT Limited, Winnipeg, Manitoba,
      Canada). PARTICIPANTS: Twenty-eight healthy young adults. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Arousals were identified using an automatic system
      followed by manual editing. The intensity of arousals was scaled (between 0 and
      9) using an automatic algorithm based on the change in the electroencephalography
      (EEG) signals' wavelet characteristics. 4,751 arousals in 28 pairs of PSGs (night
      1 and night 2) were scaled. HR responses (DeltaHR) to all arousals were
      determined and averaged at each arousal scale per file. Overall average arousal
      intensity ranged 3.0-7.1 in different subjects, and average DeltaHR ranged 1.9
      18.3 beats.min(-1). Heart rate response at a given arousal intensity, expressed
      as DeltaHR at a moderate arousal scale of 5.0 (DeltaHR5), ranged 4.1-18.1
      beats.min(-1). There was a strong correlation between arousal intensity and
      DeltaHR within each subject. More importantly, there were excellent intraclass
      correlations (ICC) between night 1 and night 2 results for all three variables
      (ICC = 0.72 for average intensity, 0.92 for average DeltaHR4, and 0.91 for
      DeltaHR5). CONCLUSIONS: Average arousal intensity and heart rate response to
      arousal are highly variable among healthy young adults and stable within
      individuals.

PMID- 25581918
TI  - Sleep Duration and Waist Circumference in Adults: A Meta-Analysis.
AB  - BACKGROUND: Previous research has demonstrated a relation between insufficient
      sleep and overall obesity. Waist circumference (WC), a measure of central
      adiposity, has been demonstrated to improve prediction of health risk. However,
      recent research on the relation of insufficient sleep duration to WC in adults
      has yielded inconsistent findings. OBJECTIVES: To assess the magnitude and the
      consistency of the relation of insufficient sleep and WC. METHODS: A systematic
      search of Internet and research databases using Google Scholar, Medline, PubMed,
      and PsycINFO through July 2013 was conducted. All articles in English with adult
      human subjects that included measurements of WC and sleep duration were reviewed.
      A random effects meta-analysis and regression analyses were performed.
      Heterogeneity and publication bias were checked. Results are expressed as Pearson
      correlations (r; 95% confidence interval). RESULTS: Of 1,376 articles, 30 met
      inclusion criteria and 21 studies (22 samples for a total of 56,259 participants)
      provided sufficient data for meta-analysis. Results showed a significant negative
      relation between sleep duration and WC (r = -0.10, P < 0.0001) with significant
      heterogeneity related to sleep comparison method. Potential moderators of the
      relation between sleep duration and WC were not significant. Funnel plots showed
      no indication of publication bias. In addition, a fail-safe N calculation
      indicated that 418 studies with null effects would be necessary to bring the
      overall mean effect size to a trivial value of r = -0.005. CONCLUSIONS:
      Internationally, cross-sectional studies demonstrate a significant negative
      relation between sleep duration and waist circumference, indicating shorter sleep
      durations covary with central adiposity. Future research should include
      prospective studies.

PMID- 25581919
TI  - The Impact of Averaging Window Length on the"Desaturation Indexes during
      Overnight Pulse Oximetry at High-Altitude".
AB  - STUDY OBJECTIVES: To determine the impact of averaging window-length on the
      "desaturation" indexes (DIs) obtained via overnight pulse oximetry (SpO2) at high
      altitude. DESIGN: Overnight SpO2 data were collected during a 10-day sojourn at
      high altitude. SpO2 was obtained using a commercial wrist-worn finger oximeter
      whose firmware was modified to store unaveraged beat-to-beat data. Simple moving
      averages of window lengths spanning 2 to 20 cardiac beats were retrospectively
      applied to beat-to-beat SpO2 datasets. After SpO2 artifacts were removed, the
      following DIs were then calculated for each of the averaged datasets: oxygen
      desaturation index (ODI); total sleep time with SpO2 < 80% (TST < 80), and the
      lowest SpO2 observed during sleep (SpO2 low). SETTING: South Base Camp, Mt.
      Everest (5,364 m elevation). PARTICIPANTS: Five healthy, adult males (35 +/- 5 y;
      180 +/- 1 cm; 85 +/- 4 kg). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: 49
      datasets were obtained from the 5 participants, totalling 239 hours of data. For
      all window lengths >= 2 beats, ODI and TST < 80 were lower, and SpO2 low was
      higher than those values obtained from the beat-to-beat SpO2 time series data (P
      < 0.05). CONCLUSIONS: Our findings indicate that increasing oximeter averaging
      window length progressively underestimates the frequency and magnitude of sleep
      disordered breathing events at high altitude, as indirectly assessed via the
      desaturation indexes.

PMID- 25581920
TI  - Sleep Concordance in Couples is Associated with Relationship Characteristics.
AB  - STUDY OBJECTIVES: Coregulation of biological systems is a defining feature of
      normative attachment in close adult relationships. Sleep is a shared, intimate
      biological process between couples; however, sleep is usually examined at the
      individual level. We examined minute-by-minute concordance in couples' actigraphy
      defined sleep-wake patterns, and how attachment style and marital satisfaction
      relate to concordance. DESIGN: Couples completed measures of avoidant and anxious
      attachment styles and relationship functioning and wore wrist actigraphs for 10
      days. Minute-by-minute concordance of sleep and wake (i.e., the percentage of
      epochs in which both partners were asleep, or both were awake) was calculated for
      each sleep period. Mixed modeling was used to account for measurement occasions
      across time. RESULTS: Percent concordance ranged from 53-88% and was not
      associated with couples' sleep quality or circadian preference. For wives,
      neither anxious nor avoidant attachment was associated with sleep-wake
      concordance. For husbands, anxious attachment style was associated with higher
      concordance, but was moderated by wives' marital satisfaction. High marital
      satisfaction in wives was associated with higher concordance, regardless of
      husbands' attachment style. In couples in which wives reported low satisfaction,
      concordance was higher when husbands had an anxious attachment style. Avoidant
      attachment style in husbands was not related to concordance. CONCLUSIONS: Sleep
      concordance provides a unique measure of couples' cosleep and varies depending on
      attachment style and relationship satisfaction.

PMID- 25581921
TI  - Web-Based Access to Positive Airway Pressure Usage with or without an Initial
      Financial Incentive Improves Treatment Use in Patients with Obstructive Sleep
      Apnea.
AB  - STUDY OBJECTIVES: We tested whether providing adults with obstructive sleep apnea
      (OSA) with daily Web-based access to their positive airway pressure (PAP) usage
      over 3 mo with or without a financial incentive in the first week improves
      adherence and functional outcomes. SETTING: Academic- and community-based sleep
      centers. PARTICIPANTS: One hundred thirty-eight adults with newly diagnosed OSA
      starting PAP treatment. INTERVENTIONS: Participants were randomized to: usual
      care, usual care with access to PAP usage, or usual care with access to PAP usage
      and a financial incentive. PAP data were transmitted daily by wireless modem from
      the participants' PAP unit to a website where hours of usage were displayed.
      Participants in the financial incentive group could earn up to $30/day in the
      first week for objective PAP use >= 4 h/day. MEASUREMENTS AND RESULTS: Mean hours
      of daily PAP use in the two groups with access to PAP usage data did not differ
      from each other but was significantly greater than that in the usual care group
      in the first week and over 3 mo (P < 0.0001). Average daily use (mean +/-
      standard deviation) during the first week of PAP intervention was 4.7 +/- 3.3 h
      in the usual care group, and 5.9 +/- 2.5 h and 6.3 +/- 2.5 h in the Web access
      groups with and without financial incentive respectively. Adherence over the 3-mo
      intervention decreased at a relatively constant rate in all three groups.
      Functional Outcomes of Sleep Questionnaire change scores at 3 mo improved within
      each group (P < 0.0001) but change scores of the two groups with Web access to
      PAP data were not different than those in the control group (P > 0.124).
      CONCLUSIONS: Positive airway pressure adherence is significantly improved by
      giving patients Web access to information about their use of the treatment.
      Inclusion of a financial incentive in the first week had no additive effect in
      improving adherence.

PMID- 25581922
TI  - An Evidence-based Analysis of the Association between Periodic Leg Movements
      during Sleep and Arousals in Restless Legs Syndrome.
AB  - STUDY OBJECTIVES: To analyze statistically the association between periodic leg
      movements during sleep (PLMS) and arousals, in order to eventually support or
      challenge the current scoring rules and to further understand their reciprocal
      influence. SETTING: Sleep research center. PATIENTS: Twenty untreated consecutive
      patients with restless legs syndrome (RLS) (13 women and 7 males, mean age 60.9
      y). METHODS: In each recording, we selected all PLMS/arousal pairs that met the
      following inclusion criteria: (a) PLMS events that were separated from another
      PLMS event (preceding or following) by at least 10 s of EMG inactivity; (b)
      arousal events separated from another arousal event (preceding or following) by
      at least 10 s of stable EEG baseline activity; (c) PLMS/arousal pairs were then
      selected among events identified according to the previous two criteria, when
      PLMS and arousals were separated (offset-to-onset) by no more than 10 s,
      regardless of which was first. MEASUREMENTS AND RESULTS: We selected a mean of
      46.1 (SD 25.55) PLMS/arousal pairs per subject; in these pairs, average PLMS
      duration was 3.2 s (0.65) and average arousal duration was 6.5 s (0.92). Within
      these event pairs, the great majority (on average 98.4%, SD 3.88) was separated
      by less than 0.5 s (i.e., between the end of one event and the onset of the
      other, regardless of which was first). Arousal onsets preceded PLMS onset in
      41.2% of pairs, while the opposite was true for the remaining 58.8% of pairs. A
      significant correlation between PLMS duration and arousal duration was also found
      (r = 0.447, P < 0.000001). CONCLUSION: The results of this study support the
      current rule for the definition of the association between periodic leg movements
      during sleep (PLMS) and arousals. The tight time relationship between PLMS and
      arousals and their correlated durations seem to indicate that both events might
      be regulated by a complex mechanism, rather than being connected by a simple
      reciprocal cause/effect relationship.

PMID- 25581924
TI  - Salt Content in IV Fluids Given Intraoperatively May Influence Postoperative OSA
      Severity.

PMID- 25581923
TI  - In Vivo Imaging of the Central and Peripheral Effects of Sleep Deprivation and
      Suprachiasmatic Nuclei Lesion on PERIOD-2 Protein in Mice.
AB  - STUDY OBJECTIVES: That sleep deprivation increases the brain expression of
      various clock genes has been well documented. Based on these and other findings
      we hypothesized that clock genes not only underlie circadian rhythm generation
      but are also implicated in sleep homeostasis. However, long time lags have been
      reported between the changes in the clock gene messenger RNA levels and their
      encoded proteins. It is therefore crucial to establish whether also protein
      levels increase within the time frame known to activate a homeostatic sleep
      response. We report on the central and peripheral effects of sleep deprivation on
      PERIOD-2 (PER2) protein both in intact and suprachiasmatic nuclei-lesioned mice.
      DESIGN: In vivo and in situ PER2 imaging during baseline, sleep deprivation, and
      recovery. SETTINGS: Mouse sleep-recording facility. PARTICIPANTS:
      Per2::Luciferase knock-in mice. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Six
      hour sleep deprivation increased PER2 not only in the brain but also in liver and
      kidney. Remarkably, the effects in the liver outlasted those observed in the
      brain. Within the brain the increase in PER2 concerned the cerebral cortex
      mainly, while leaving suprachiasmatic nuclei (SCN) levels unaffected. Against
      expectation, sleep deprivation did not increase PER2 in the brain of arrhythmic
      SCN-lesioned mice because of higher PER2 levels in baseline. In contrast, liver
      PER2 levels did increase in these mice similar to the sham and partially lesioned
      controls. CONCLUSIONS: Our results stress the importance of considering both
      sleep-wake dependent and circadian processes when quantifying clock-gene levels.
      Because sleep deprivation alters PERIOD-2 in the brain as well as in the
      periphery, it is tempting to speculate that clock genes constitute a common
      pathway mediating the shared and well-known adverse effects of both chronic sleep
      loss and disrupted circadian rhythmicity on metabolic health.

PMID- 25581925
TI  - The brave new world of healthcare delivery: just where are we in our
      understanding of e-health methods for insomnia and depression management?

PMID- 25581926
TI  - Resilience and readiness through restorative sleep.

PMID- 25581927
TI  - Does sleep apnea damage the kidneys?

PMID- 25581928
TI  - Vitamin D associations and sleep physiology-promising rays of information.

PMID- 25581930
TI  - [The effects of intermittent hypobaric hypoxia on myocardial ischemia/reperfusion
      injury and ZFP580 expression].
AB  - OBJECTIVE: To elucidate whether ZFP580 is involved in the cardioprotective
      effects of intermittent hypobaric hypoxia (IHH) against myocardial
      ischemia/reperfusion (I/R) injury. METHODS: Thirty two male Wistar rats were
      randomly divided into 2 groups (n = 16): normoxia control group and IHH
      preconditioning group. Rats in IHH group were exposed in a hypobaric chamber
      (equivalent to an altitude of 5 000 m) for a 6 h period each day for 42 d. Plasma
      was collected and lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were
      measured after 2 h of myocardial I/R injury. ZFP580 protein expression in
      myocardial tissue was assayed by Western blot. Other 8 rats in each group were
      used to evaluate I/R-induced cardiac infarction by TTC staining. Lentivirus
      mediated gene transfection was performed in H9c2 cells 72 h prior to simulated
      ischemia/reperfusion (SI/R) exposure. The degree of cell apoptosis was determined
      by annexin V/7-AAD staining and flow cytometry analysis. RESULTS: Compared with
      normoxia control group, adaptation to IHH attenuated infarct size and plasma
      leakage of LDH and CK-MB. In addition, ZFP580 expression in the myocardium was up
      regulated by IHH. The results of gene transfection showed that ZFP580
      overexpression significantly inhibited cells apoptosis induced by SI/R.
      CONCLUSION: Our findings demonstrate that the cardioprotective effect of IHH
      against I/R injury is mediated via ZFP580, a novel transcription factor, with
      anti-apoptotic roles in myocardial cells.

PMID- 25581931
TI  - [Aerobic exercise and the effect of melatonin on experimental study on the
      effects of antioxidant activity in diabetic rats].

PMID- 25581932
TI  - [Effect of MI history on perioperative cardiovascular events in elderly CHD
      patients].

PMID- 25581929
TI  - Vitamin D and actigraphic sleep outcomes in older community-dwelling men: the
      MrOS sleep study.
AB  - STUDY OBJECTIVES: Maintaining adequate serum levels of vitamin D may be important
      for sleep duration and quality; however, these associations are not well
      understood. We examined whether levels of serum 25(OH)D are associated with
      objective measures of sleep in older men. SETTING AND PARTICIPANTS: Cross
      sectional study within a large cohort of community-dwelling older men, the MrOS
      study. INTERVENTIONS: Among 3,048 men age 68 years or older, we measured total
      serum vitamin D. Objective estimates of nightly total sleep time, sleep
      efficiency, and wake time after sleep onset (WASO) were obtained using wrist
      actigraphy worn for an average of 5 consecutive 24-h periods. RESULTS: 16.4% of
      this study population had low levels of vitamin D (< 20.3 ng/mL 25(OH)D). Lower
      serum vitamin D levels were associated with a higher odds of short (< 5 h) sleep
      duration, (odds ratio [OR] for the highest (>= 40.06 ng/mL) versus lowest (< 20.3
      ng/mL) quartile of 25(OH)D, 2.15; 95 % confidence interval (CI), 1.21-3.79;
      Ptrend = 0.004) as well as increased odds of actigraphy-measured sleep efficiency
      of less than 70% (OR, 1.45; 95% CI, 0.97-2.18; Ptrend = 0.004), after controlling
      for age, clinic, season, comorbidities, body mass index, and physical and
      cognitive function. Lower vitamin D levels were also associated with increased
      WASO in age-adjusted, but not multivariable adjusted models. CONCLUSIONS: Among
      older men, low levels of total serum 25(OH)D are associated with poorer sleep
      including short sleep duration and lower sleep efficiency. These findings, if
      confirmed by others, suggest a potential role for vitamin D in maintaining
      healthy sleep.

PMID- 25581933
TI  - [Analysis on the characteristics of microcirculatory blood flow in different
      muscles of elite rowers].

PMID- 25581934
TI  - Playing newborn intracranial roulette: parental refusal of vitamin K injection.

PMID- 25581935
TI  - Fear factor. Two viruses have created an epidemic of anxiety about deadly
      infections in America. Here's how managing fear can give us an edge over disease.

PMID- 25581936
TI  - Targeting glioblastoma cancer stem cells: the next great hope?
AB  - Glioblastoma multiforme (GBM) is the most common primary brain tumor and is
      notorious for its poor prognosis. The highly invasive nature of GBM and its
      inherent resistance to therapy lead to very high rates of recurrence. Recently, a
      small cohort of tumor cells, called cancer stem cells (CSCs), has been recognized
      as a subset of tumor cells with self-renewal ability and multilineage capacity.
      These properties, along with the remarkable tumorigenicity of CSCs, are thought
      to account for the high rates of tumor recurrence after treatment. Recent
      research has been geared toward understanding the unique biological
      characteristics of CSCs to enable development of targeted therapy. Strategies
      include inhibition of CSC-specific pathways and receptors; agents that increase
      sensitivity of CSCs to chemotherapy and radiotherapy; CSC differentiation agents;
      and CSC-specific immunotherapy, virotherapy, and gene therapy. These approaches
      could inform the development of newer therapeutics for GBM.

PMID- 25581937
TI  - Hypoxia-inducible factor-1 and associated upstream and downstream proteins in the
      pathophysiology and management of glioblastoma.
AB  - Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with an
      exceptionally poor patient outcome despite aggressive therapy including surgery,
      radiation, and chemotherapy. This aggressive phenotype may be associated with
      intratumoral hypoxia, which probably plays a key role in GBM tumor growth,
      development, and angiogenesis. A key regulator of cellular response to hypoxia is
      the protein hypoxia-inducible factor-1 (HIF-1). An examination of upstream
      hypoxic and nonhypoxic regulation of HIF-1 as well as a review of the downstream
      HIF-1- regulated proteins may provide further insight into the role of this
      transcription factor in GBM pathophysiology. Recent insights into upstream
      regulators that intimately interact with HIF-1 could provide potential
      therapeutic targets for treatment of this tumor. The same is potentially true for
      HIF-1-mediated pathways of glycolysis-, angiogenesis-, and invasion-promoting
      proteins. Thus, an understanding of the relationship between HIF-1, its upstream
      protein regulators, and its downstream transcribed genes in GBM pathogenesis
      could provide future treatment options for the care of patients with these
      tumors.

PMID- 25581939
TI  - [Experience of operator may be more crucial than withdrawal time of colonoscopy
      for the detection of colonic neoplasm].

PMID- 25581940
TI  - The future of veterinary compounding.

PMID- 25581938
TI  - Bevacizumab for glioblastoma: current indications, surgical implications, and
      future directions.
AB  - Initial enthusiasm after promising Phase II trials for treating recurrent
      glioblastomas with the antiangiogenic drug bevacizumab-a neutralizing antibody
      targeting vascular endothelial growth factor-was tempered by recent Phase III
      trials showing no efficacy for treating newly diagnosed glioblastomas. As a
      result, there is uncertainty about the appropriate indications for the use of
      bevacizumab in glioblastoma treatment. There are also concerns about the effects
      of bevacizumab on wound healing that neurosurgeons must be aware of. In addition,
      biochemical evidence suggests a percentage of tumors treated with bevacizumab for
      an extended period of time will undergo transformation into a more biologically
      aggressive and invasive phenotype with a particularly poor prognosis. Despite
      these concerns, there remain numerous examples of radiological and clinical
      improvement after bevacizumab treatment, particularly in patients with recurrent
      glioblastoma with limited therapeutic options. In this paper, the authors review
      clinical results with bevacizumab for glioblastoma treatment to date, ongoing
      trials designed to address unanswered questions, current clinical indications
      based on existing data, neurosurgical implications of bevacizumab use in patients
      with glioblastoma, the current scientific understanding of the tumor response to
      short- and long-term bevacizumab treatment, and future studies that will need to
      be undertaken to enable this treatment to fulfill its therapeutic promise for
      glioblastoma.

PMID- 25581942
TI  - [Can low FODMAP diet be considered as first-line therapy in the management of
      irritable bowel syndrome?].

PMID- 25581941
TI  - [Massive upper gastrointestinal bleeding from multiple gastrointestinal stromal
      tumor in a neurofibromatosis patient].

PMID- 25581943
TI  - Caregivers program. Final rule.
AB  - The Department of Veterans Affairs (VA) adopts, with changes, the interim final
      rule concerning VA's Program of Comprehensive Assistance for Family Caregivers.
      VA administers this program to provide certain medical, travel, training, and
      financial benefits to caregivers of certain veterans and servicemembers who were
      seriously injured during service on or after September 11, 2001. Also addressed
      in this rulemaking is the Program of General Caregiver Support Services that
      provides support services to caregivers of veterans from all eras who are
      enrolled in the VA health care system. Specifically, changes in this final rule
      include a requirement that Veterans be notified in writing should a Family
      Caregiver request revocation (to no longer be a Family Caregiver), an extension
      of the application timeframe from 30 days to 45 days for a Family Caregiver, and
      a change in the stipend calculation to ensure that Primary Family Caregivers do
      not experience unexpected decreases in stipend amounts from year to year.

PMID- 25581944
TI  - Pain management: strategic guidelines.

PMID- 25581945
TI  - Metabolic syndrome a widespread threatening condition; risk factors, diagnostic
      criteria, therapeutic options, prevention and controversies: an overview.
AB  - Metabolic syndrome diagnostic criteria include at least three of five of the
      following medical conditions: abdominal obesity, high blood pressure, abnormal
      high fasting plasma glucose, elevated serum triglycerides and low HDL (high
      density cholesterol) level. Sedentary, overweight and obesity are
      characteristically associated with the syndrome, nevertheless there are new
      studies which indicate that chronic stress, through deregulation of the
      hypothalamic-pituitary-adrenal (HPA) axis is also involved in the development of
      the syndrome. Metabolic syndrome represents a significant risk for the
      development of the cardiovascular diseases. New studies in the USA have estimated
      its prevalence at approximately 34% of the adult population and its prevalence is
      increasing with age. Diagnosis guidelines are establishing the metabolic syndrome
      diagnostic when are met three of the following five conditions: fasting glucose >
      or = 100 mg/dL or type 2 diabetes receiving drug therapy for hyperglycemia; high
      blood pressure > or = 130/85 mm Hg or high blood pressure receiving drug therapy;
      triglycerides > or =150 mg/dL or treatment for plasma hyper-triglyceride value;
      HDL-C < 40 mg/dL in men and < 50 mg/dL in women or if under therapy for reduced
      HDL-C levels and waist circumference of > or = 102 cm in men and > or = 88 cm in
      women. Besides important change of lifestyle, often drug therapy is needed
      (diuretics and ACE inhibitors, cholesterol drugs and weight loss medications).
      The value of physical activity and diet in prevention and treatment of the
      syndrome is supported by numerous studies. Association of metabolic syndrome and
      cardiovascular risk is still a matter of controversy, in what concerns the lack
      of significant cardiovascular risk in the case of obesity itself without
      metabolic syndrome.

PMID- 25581946
TI  - Iron hypothesis of cardiovascular disease: still controversial.
AB  - Iron hypothesis has been a controversial subject for over 30 years as many
      studies support its role as a risk factor for cardiovascular disease, while other
      studies found no evidence to support it. The conflicting results are accounted
      for by the non-homogeneity of trial design in terms of population inclusion
      criteria and different endpoints, non-uniform use of parameters for assessing
      iron role, and incomplete understanding of the mechanisms of action. The nature
      of iron is dual, being of crucial importance for the human body, but also toxic
      as "free iron" induces oxidative stress. Under physiological conditions, there
      are efficient and complex mechanisms against iron-induced oxidative stress, which
      could be reproduced for creating new, intelligent antioxidants. Iron depletion
      improves the cardiovascular prognosis only if serum concentration is at the
      lowest limit of normal ranges. However, low iron levels and the type of dietary
      iron intake correlate with atherosclerotic cardiovascular disease, influence the
      ischemic endpoints in the elderly, and exert negative impact on heart failure
      prognosis. So far, the causal relation and involved mechanisms are not fully
      elucidated. Iron overload is a difficult and frequent condition, involving the
      cardiovascular system by specific pathogenic pathways, therefore determining a
      particular form of restrictive cardiomyopathy and vaso-occlusive arterial damage.

PMID- 25581947
TI  - Alcoholic liver disease--epidemiology and risk factors.
AB  - Alcoholic liver disease (ALD) accounts for the majority of chronic liverdiseases
      in Occidental countries and remains a major cause of liver-related mortality in
      worldwide. The spectrum of ALD includes steatosis in patients which consume over
      80g of alcohol per day, alcoholic steatohepatitis and liver cirrhosis in
      approximately 15% of patients. Once cirrhosis is established, the annual risk for
      hepatocellular carcinoma is about 1-2%. Environmental factors such as drinking
      patterns, coexisting liver disease, obesity, diet and co-medication may affect
      the natural course of ALD. Abstinence is the hallmark of therapy for ALD, and
      nutritional therapy is the first line in therapeutical intervention.

PMID- 25581948
TI  - Is there a cardiovascular risk in inflammatory bowel diseases?
AB  - Inflammatory bowel diseases (IBD) are characterized by an increased thrombembolic
      risk, given the powerful relation between inflammation and thrombosis. Multiple
      studies showed that patients with IBD have an up to 3-fold higher risk for
      developing venous thrombembolic (VTE) complications compared to general
      population, this risk being more increased in the hospitalized IBD flares. Thus,
      latest consensus recommendations indicate prophylaxis for VTE in hospitalized
      patients with active IBD but with no clear indications for the management of IBD
      outpatients. Regarding atherothrombotic risk (myocardial infarction or stroke),
      up-to-date data are inconclusive. IBD is associated with subclinical
      atherosclerosis in patients without clinical manifestations of cardiovascular
      diseases (CVD). However, the results of major studies assessing the hypothesis
      that IBD is strongly associated with atherosclerotic macrovascular events prove
      to be divergent even if they show positive correlations with CVD especially on
      different subgroup analysis. These facts should lead in the future to more
      prospective studies with control groups that have the same cardiovascular risk
      profile as in IBD populations in order to admit definitively that patients with
      IBD are exposed to an increased cardiovascular risk.

PMID- 25581949
TI  - Prognostic factors in resectable pancreatic cancer.
AB  - The pancreatic cancer is a disease with exponentially increased incidence,
      especially over the last decades, being the sixth or even fifth cause of death by
      cancer in most of the modern societies. Moreover, it is estimated that almost 95%
      of the patients with this disease are presenting to the doctor in the advanced
      and unresectable stages. Also, over the past few decades the development and
      advance of the surgical methods and techniques have improved only morbidity and
      hospital postoperative mortality, without significant impact on survival. In this
      way, in the present mini-review we want it to make a short description for some
      modern aspects regarding the factors implicated in pancreatic cancer survival.

PMID- 25581950
TI  - The importance of clinical prediction models in non-fatal pulmonary embolism: an
      analysis of the best known clinical scores.
AB  - The clinical evaluation in pulmonary embolism (PE) is the first instrument used
      by practitioners in the management of this potentially fatal pathology. The
      necessity of develop- ing certain valid and especially affordable practical
      instruments has led to the emergence of various clinical prediction models. The
      purpose of this paper is to analyze the main clinical scores, as a diagnostic or
      a prognostic tool, with their strengths and weaknesses. The PESI score, while
      relatively recent, remains the most investigated and validated prognostic score
      for the identification of the mortality risk and major adverse events, with
      economic implications of health services reduction costs through the accurate
      identification of patients with a low risk who are candidates of early hospital
      discharge. The simplified Geneva score (with a similar accuracy as the Geneva
      one) identifies a high or low PE probability, especially in combination with D
      dimers, with a prognosis value as well. The Wells and simplified Wells scores
      identify the high or low probability, being improved by the level of D-dimers,
      having similar results with the Geneva score. The LR-PED score, conceived as an
      identification score for low risk, uses biochemical and electrocardiographic
      markers, but is less validated. The Vienna Prediction Model is another system for
      the evaluation of the recurrence in which the level of D-dimers is the main
      prediction factor. Other scores were evaluated with a statistically low
      significance. The Geneva and the PESI scores remain the most valuable instruments
      of diagnosis and clinical prognostic, respectively.

PMID- 25581951
TI  - Acute gout attack with normal serum uric acid levels.
AB  - AIM: The paper aims to determine the prevalence of clinical cases with acute gout
      attacks and normal serum uric acid levels. MATERIAL AND METHODS: This
      retrospective study was conducted between October, 2013 and June, 2014 in 30
      patients diagnosed with acute gout attack admitted to the 1st Clinic of
      Rheumatology of Iasi. The diagnosis was based on clinical manifestations and
      positive response to therapeutic test with colchicine. RESULTS: Normal serum uric
      acid levels were found in 63.3% of the patients with acute gout attack. The
      inflammatory syndrome was detected in 76.6% of patients with high erythrocyte
      sedimentation rate (ESR) levels and in 30% of patients who had elevated C
      reactive protein levels. The urinary excretion of uric acid was measured in 11
      patients and it was found increased in 55% of them. CONCLUSIONS: The diagnosis of
      acute gout attack should not be excluded in the presence of normal serum uric
      acid levels if the clinical manifestations or the positive response at colchicine
      are suggestive of gout. The low uric acid level is correlated with increased
      inflammatory factors and urinary excretion of uric acid.

PMID- 25581952
TI  - Associated factors of ejection fraction in insulin-treated patients with type 2
      diabetes.
AB  - AIM OF THE STUDY: to evaluate the relation between ejection fraction (EF),
      diabetes characteristics and cardiovascular risk factors. MATERIAL AND METHODS:
      We carried out a cross-sectional study in 171 patients with insulin-treated type
      2 diabetes hospitalized at the Sf. Spiridon Emergency Clinical Hospital, Iasi.
      All patients were evaluated for asymptomatic organ damage and cardiovascular risk
      factors of hypertension and diabetes metabolic control. Global ejection fraction
      (EF) was evaluated through 2-D echocardiography. RESULTS AND DISCUSSION: In the
      studied group the ejection fraction had significant negative correlations with
      the duration of the disease (p=0.007) and the presence of microalbuminuria
      (p=0.001). There were some differences between the categories realized by
      grouping the patients according to the presence of hypertension and/or previous
      myocardial infarction. In patients without personal history of cardiovascular
      disease EF was correlated only with LDLc levels. In the hypertensive patients
      without myocardial infarction it was correlated with diabetes duration, Hb A1e
      and LDLc, In those patients with both conditions, EF had significant correlations
      with Hb A1e and microalbuminuria. CONCLUSIONS: These results emphasized that the
      determinants associated with heart failure in patients with type 2, insulin
      treated diabetes, differ according to the presence of high blood pressure and
      myocardial infarction.

PMID- 25581953
TI  - Cutaneous manifestations associated with thyroid disease.
AB  - AIM: To present the clinical and laboratory features of patients with
      dermatologic disorders associated with thyroid diseases, diagnostic criteria,
      type of administered treatment and its effectiveness. MATERIAL AND METHODS: This
      study is a retrospective study based on the medical records of patients with
      thyroid diseases admitted to the Dermato venereology Clinic of the Iasi "Sf.
      Spiridon" University Emergency Hospital between January 1, 2012-December 31,
      2013. Data on clinical manifestations, methods of investigation, therapeutic
      approach, and associated dermatologic and systemic diseases were reviewed.
      RESULTS: A total of 38 patients were enrolled in this study of which 36 females
      and two males. An high incidence of cases with autoimmune thyroiditis (63%),
      followed by polynodular goiter (26.3%) and hypothyroidism (10.7%) was found
      during the study. The identified dermatologic disorders associated with thyroid
      diseases were in order of frequency alopecia areata (22%), followed by lichen
      planus (18%). CONCLUSIONS: This study demonstrates that there is a significant
      association between certain dermatologic disorders and thyroid diseases,
      requiring periodic thyroid function tests.

PMID- 25581955
TI  - The correlation between the ankle-brachial index and the metabolic syndrome. .
AB  - On a global scale, the cardiovascular diseases constitute the prime factor of
      death and invalidity. The premature mortality percentage caused by these varies
      from 4% in high developed countries to 40% in underdeveloped countries.
      Atherosclerosis is the most important etiological factor. The presence of various
      degrees of atherosclerosis in a certain vascular area (in our case, the lower
      limb arteries), increases the probability of affecting other areas as well
      (coronary, cerebral, renal, mesenteric arteries). AIM: The evaluation and
      description of the correlations between the ankle-brachial index levels and the
      cardiovascular risk factors, taken individually or as part of the metabolic
      syndrome. MATERIAL AND METHOD: The values of the ankle-brachial index were
      divided in normal and abnormal. The evaluated cardiovascular risk factors were:
      age, sex, arterial hypertension, obesity, smoking, high levels of cholesterol and
      basal glucose, low levels of HDL-cholesterol. RESULTS: There were significant
      statistical differences between the normal ankle-brachial index lot and the one
      with abnormal values, specifically in patients with diabetes mellitus and
      metabolic syndrome. More so, the study demonstrates that the ankle-brachial index
      is considerably smaller in patients with metabolic syndrome. CONCLUSIONS: The
      simple measurement of the afore mentioned index, as a atherosclerosis marker for
      the lower limb arteries, represents an independent prediction over the metabolic
      syndrome and the conventional risk factors, in the development of the
      cardiovascular diseases. The routine measurement of this parameter in medical
      practice might imply the early diagnosis of high risk manifested cardiovascular
      disease patients.

PMID- 25581956
TI  - Butyrylcholinesterase activity-biomarker for predicting the outcome in acute
      cholinesterase inhibitor poisoning--a 30-year retrospective analysis.
AB  - AIM: To assess the role of butyrylcholinesterase (BuChE) activity as a predictive
      biomarker in acute cholinesterase inhibitor poisoning in a cohort from a regional
      tertiary care hospital. MATERIAL AND METHODS: Plasma butyrylcholinesterase
      activity on admission and at regular intervals during admission and clinical
      outcomes of cases admitted to the Toxicology Clinic of "Sf. Spiridon" Emergency
      Hospital Iasi, Romania between 1983 and 2013 were evaluated. RESULTS: A total
      number of 606 patients were included in the study. The mean BuChE-activity level
      on admission was 1.54 ml NaOH N/100. A correlation between the amount of ingested
      organophosphates/carbamates (OPs/CMs) and low cholinesterase activity on
      admission was found. 66.66% of the patients were admitted to hospital within 8
      hours after poisoning. The initial, daily and mean total atropine doses
      administrated were 9.65 mg, 10.51 mg and 69.39 mg, respectively. 67.16% of the
      investigated patients received Toxogonin for 6.41 days showing a slow increase in
      BuChE activity afterwards. The average number of hospital days was 11.22. The
      study revealed that complications occurred in patients with BuChE-activity levels
      below 1.4 mL NaOH N/100. A positive correlation between mortality rate (3.8% of
      patients) and the lowest BuChE-activity level on admission (0.89 mL NaOH N/100)
      was found. CONCLUSIONS: BuChE activity on admission and its level during hospital
      stay represent an important predictive factor for acute cholinesterase inhibitors
      poisoning.

PMID- 25581954
TI  - Therapeutic particularities in amiodarone induced thyroid disorder in patients
      with underlying cardiac condition.
AB  - AIM: the analysis of therapeutic approach in patients with basic heart condition
      and amiodarone induced thyroid dysfunction--correlations with the evolution and
      prognosis. MATERIAL AND METHODS: The study included 215 patients, 90 men and 125
      women aged between 35 and 87, with different cardiac pathologies hospitalized in
      the Cardiology Clinic between 2004-2014, who received amiodarone treatment, in
      most cases for prophylaxis of various arrhythmias, both supraventricular and
      ventricular. During the evolution, these patients have developed amiodarone
      induced thyroid dysfunction (hypo- or hyper function). RESULTS AND DISCUSSION:
      The evaluation of thyroid function after starting treatment was performed in 187
      patients (86.97%). Diagnosis of amiodarone-induced thyroid dysfunction was based
      on hormonal dosages of TSH, FT4 and FT3, endocrinological examination and thyroid
      ultrasound. Thyroid dysfunction treatment was initiated, depending on the
      situation, in all patients during the hospitalization. Treatment included anti
      thyroid drugs or hormones substitution and in some cases a minimal dose of
      prednisone. CONCLUSIONS: Thyroid dysfunction regardless of the type (with hypo-
      or hyper function) requires continuous changes of the cardiovascular treatment,
      and association, where appropriate, with thyroid dysfunction medication. In some
      cases the latter determines cardiovascular side effects, for instance
      corticotheraphy may become a factor of imbalance for the hemodynamic status of
      the patient (by fluid retention, increased blood pressure, hyper glycemia).

PMID- 25581957
TI  - Computerized calculation of breast density: our experience from Arcadia Medical
      Imaging Center.
AB  - THE AIM OF THIS STUDY: To implement a spatial fuzzy C-means algorithm for image
      segmentation and breast tissue density quantification and compare it with BI-RADS
      breast density classes determined by radiologists. MATERIAL AND METHODS: The
      analysis was based on 206 mammograms performed in 111 women with various breast
      abnormalities. Digitized mammographic films were independently double read by
      radiologists certified in breast diagnosis, followed by consensus with
      arbitration agreement (radiological ground truth). Reporting was done using the
      BI-RADS mammography lexicon. Using an algorithm based on a combination of spatial
      fuzzy C-means clustering and binary thresholding, percent mammographic density
      was computed in digitized mammograms. The BI-RADS breast density readings were
      compared with percent breast density measurements determined by computer
      algorithm. RESULTS: The algorithm was found to match the BI-RADS density
      classification in 90% of the cases, with an excellent agreement (kappa = 0.88)
      between the radiological ground truth versus the algorithm breast tissue density
      estimates. CONCLUSIONS: Our study proposed an algorithm that can be applied both
      to digitized and digital mammograms, which proved to be effective in breast
      density estimates. The method can accurately determine the percentage density
      removing the human observer variability. The proposed method showed an excellent
      agreement with radiological ground truth.

PMID- 25581958
TI  - Celiac disease: 10-year experience in a Romanian tertiary center.
AB  - AIM: To evaluate the experience of a single coeliac center over a 10-year
      observational period. MATERIAL AND METHODS: Between January 2003 and December
      2013 a total of 195 consecutive patients admitted with celiac disease were tested
      by multiple duodenal biopsies, anti-tissue transglutaminase and anti-gliadin
      antibodies, and baseline demographic, clinical, biological and immunological
      parameters. RESULTS: Patients were divided into two major groups according to the
      clinical features and number of signs and symptoms present upon admission:
      gastrointestinal (131, 67.17%) and non-gastrointestinal (64, 32.8%). Anti-tissue
      transglutaminase and anti-gliadin antibodies showed seropositivity in 109/158.
      Histological samples were available in 152 cases, according to Marsh-Oberhuber
      classification 11.18% being type 0, 17.76%, type I-II, and 71.05% type III.
      Correlations between anti-tissue transglutaminase antibody titers and Marsh
      Oberhuber classification were found to be statistically significant. Body mass
      index was available in 96 cases. We found that severe atrophy was predominant in
      patients with a BMI<18 kg/m2. CONCLUSIONS: Celiac disease has an increasing
      prevalence and can be diagnosed at any age. Histology samples were indicative of
      different stages of villous atrophy. The disease prevalence is significantly
      higher among women. There was no statistically significant correlation between
      Marsh classification and BMI values.

PMID- 25581959
TI  - Fibrosis assessment in chronic hepatitis C--is the liver biopsy still necessary?
      The pathologist point of view.
AB  - AIM: The aim of this study was to compare the histological stage of fibrosis
      determined by liver biopsy with the stage of fibrosis assessed by Fibroscan, to
      analyze the correspondences and inconsistencies between obtained values and to
      discuss the role of the microscopic exam, from the pathologist point of view.
      MATERIAL AND METHODS: The study group consisted of 185 patients diagnosed with
      chronic hepatitis. Serological tests diagnosed chronic hepatitis C in 183
      patients, and chronic hepatitis B and C for 2 patients. The patients were
      evaluated to determine the stage of fibrosis using two methods: liver biopsy and
      elastography (Fibroscan). RESULTS: Based on the pathologic evaluation, 124 cases
      were diagnosed as moderate chronic hepatitis (score 6-8), and the remaining 60
      cases as severe hepatitis (score 9-12). Comparison of data from examination of
      liver biopsy with that obtained by Fibroscan examination revealed overlapping and
      divergent aspects. The fibrosis stage established through liver biopsy did not
      always coincide with the one assigned by liver stiffness measurement,
      particularly for intermediate stages F2 and F3. The best overlap was noted for F0
      F1 and F4 stages, which indicates the evident ability of transient elastography
      to separate patients with minimal or no fibrosis from patients with extensive
      fibrosis. CONCLUSIONS: Our data concurs with the literature, which confirms
      presence of differences between Fibroscan and biopsy. From the point of view of
      the pathologist, liver biopsy still remains a valuable instrument, offering a
      relevant image of liver changes--as it is regarded more rather a selective than
      routine technique.

PMID- 25581960
TI  - Chronic venous disease cases at the Iasi dermatology clinic.
AB  - Chronic venous disease (CVD) is defined as a disturbance of blood return to the
      deep venous system, superficial venous system, and communicating (perforating)
      veins. Once present, CVD persists throughout life, so like heart failure it is
      nowadays considered "a condition for life". Severe CVD of the lower limbs is one
      of the most common medical problems, affecting up to 25% of the general adult
      population of industrialized countries. AIM: to determine the incidence of CVD
      among the cases admitted to the Dermatology Clinic of the' "Sf. Spiridon"
      Emergency Clinical Hospital Iasi, CVD incidence by sex, age, area of residence
      and the main pathogens incriminated in super infection of ulcerative lesions.
      MATERIAL AND METHODS: We did a retrospective study of patients admitted to the
      Dermatology Clinic of the Iasi "Sf. Spiridon" Emergency Hospital over a five
      years period. RESULTS: Of the total number of patients admitted to our clinic
      (9375), 57% were diagnosed with CVD and 26.61% of them were with CEAP 6 class
      chronic venous insufficiency. There was an approximately equal sex distribution
      and most patients (44%) were older than 65 years. CONCLUSIONS: We did a large
      epidemiological study of venous disease, based on revised CEAP classification,
      showing again that it is not only a very important medical problem, with various
      clinical manifestation and multidisciplinary approach, but also an important
      issue for health insurance system.

PMID- 25581961
TI  - Napkin psoriasis--case report.
AB  - Psoriasis is a chronic inflammatory disease that can affect up to 1% of children.
      Genetic (family history of psoriasis) and environmental factors (bacterial or
      viral infections, stress, and trauma) are frequently involved in its occurrence.
      Napkin psoriasis is a particular form of psoriasis affecting mainly children
      younger than 2 years of age and can be classified together with other diseases
      under diaper rash. We present the case of a 4-month-old infant, born at term,
      naturally, weight and height within the normal range, who was brought to the
      Dermatology Clinic for the occurrence of erythematosquamous lesions in the
      anogenital area, buttocks and upper third of the thighs, with subsequent
      dissemination of lesions. The onset of symptoms began a few days after a
      respiratory tract infection. Initially he received treatment with systemic
      antibiotic and topical corticosteroid and antibiotic with unfavorable outcome.
      Laboratory tests revealed iron-deficiency anemia, leukocytosis, thrombocytosis,
      accelerated ESR, marked hepatic cytolysis, hyperphosphatemia and nasal carriage
      of Staphylococcus aureus. A systemic antihistamine and nonspecific
      desensitization treatment was administered. Topical treatment consisted in the
      removal of predisposing factors and irritants (diaper, urine) by rigorous
      hygiene, application of topical non-fluorinated cortico-steroid and use of
      emollients, with favorable course of the lesions. The peculiarity of the case is
      that the diagnosis of psoriasis was based on history, physical examination and
      laboratory tests, in the absence of a pathology examination to confirm the
      diagnosis. Pathology examination could not be performed due to patient's age as
      biopsy required general anesthesia.

PMID- 25581962
TI  - Jod-Basedow effect due to prolonged use of lugol solution-case report.
AB  - Graves' disease is the most common form of hyperthyroidism, accounting for 60-80%
      of all cases of thyrotoxicosis. If left untreated, it may lead to severe
      thyrotoxicosis with cardiovascular, ocular, psychiatric complication, and in
      extreme cases thyrotoxic crisis with a high mortality rate. We present the case
      of a 50-years-old woman diagnosed in another service with Graves' disease and
      treated for many years with antithyroid drugs (ATDs), admitted to our service for
      a relapse due to treatment discontinuation. The surgical treatment was planned
      and the preoperative preparation with Lugol solution was initiated. Due to a
      misunderstanding, the administration of iodine solution was extended for a period
      of about 30 days, thus generating the so-called Jod-Basedow effect, with the
      exacerbation of the manifestations of thyrotoxicosis and risk of thyroid storm.
      The patient received treatment with high ATDs doses, glucocorticoids, and beta
      blockers, resulting in the progressive improvement of symptoms. She was
      discharged from hospital and given the risk of thyrotoxic crisis the surgery was
      postponed. After a month, the patient underwent thyroidectomy without
      preoperative preparation with iodine solution. The operative and postoperative
      courses were uneventful.

PMID- 25581963
TI  - Metastatic carcinoid tumor--atypical presentation.
AB  - Carcinoid tumor is a slow-growing type of neuroendocrine tumor, originating in
      the enterochromaffin cells and secreting mainly serotonin. Neuroendocrine tumors
      (NETs) are found throughout the intestinal tract, the appendix and terminal ileum
      being the most common locations, and are classified by site of origin and by
      degree of differentiation, with well-differentiated lesions representing those
      tumors formerly referred to as carcinoid tumors. The clinical symptoms are
      characterized by flushing, diarrhea, abdominal pain, and/or bronchial
      constriction and occur almost exclusively in patients with liver metastases due
      to the release of bioactive peptides and amines directly into the systemic
      circulation. We report the clinical, serological and histological diagnosis of a
      67-years-old male patient with congestive heart failure secondary to carcinoid
      heart disease in the context of liver metastases of an ileum carcinoid tumor.

PMID- 25581964
TI  - Treatment of proximal humeral fractures using telegraph rod: retrospective study
      of 47 cases.
AB  - AIM: To assess the early results observed in a series of patients treated with a
      first-intention Telegraph rod. MATERIAL AND METHODS: In the interval 2011-2013
      forty-seven patients with fractures of the upper extremity of the humerus were
      assessed both clinically and radiologically. Mean follow-up was 8.9 months. The
      median age was 61 years. The study group included 39 women and 8 men, the left
      shoulder being most commonly affected (33 cases). Cause of injury was accidental
      fall in 39 cases fall, sports injury in 6 cases, and car crash injury in 2 cases.
      Neer classification was used to assess the type of fracture. For qualitative
      analysis, we used the functional Constant-Murley score in comparison with the
      contralateral side. The analysis of fracture reduction was based on plain X-rays
      in anterior-posterior plane and measurement of humeral head tilt relative to
      diaphyseal shaft. RESULTS: No case showed infection, humeral head necrosis
      occurred in 2 cases, loss of reduction in 3 cases which required repeat
      reduction, and a subacromial impingement syndrome in 2 cases. Average Constant
      Murley score was 70.33 points for the injured and 86.4 points for the healthy
      shoulder. Mean value of reduction angle of the humeral head relative to
      diaphyseal shaft was 33.75 degrees (range 3 to 81 degrees). CONCLUSIONS:
      Telegraph rods provide a secure fit in extra-articular and simple articular
      fractures of the proximal humerus. When performing a closed anatomical reduction,
      the method provides good functional results in most patients. This option should
      be considered in young patients and even in the elderly, the results being
      comparable to those obtained by hemiarthroplasty.

PMID- 25581965
TI  - Obstetrical trauma--therapeutic dilemmas?
AB  - Obstetrical trauma is frequent among newborns alive and could represent a cause
      of perinatal death. The aim of this paper consists of presenting the authors
      experience regarding the diagnosis and treatment of skeletal and thoracic
      abdominal organs related to traumatic birth. MATERIAL AND METHODS: Between 2000
      and 2010, 33 patients with trauma at birth were included in the study. The type
      of the lesion and the therapeutical approach and results were analyzed. RESULTS:
      Two categories of results were clearly differentiated: excellent for obstetric
      trauma involving limbs and soft parts and negative, disappointing results with 10
      deaths in 12 cases treated for obstetric trauma of abdominal organs. CONCLUSIONS:
      Bone and soft tissue birth trauma are relatively easy to identify and treat, but
      the medical approach of thoraco-abdomnial organs birth trauma need clinical
      experience and technical possibilities.

PMID- 25581966
TI  - Surgical techniques in the treatment of multilevel arterial occlusive disease.
AB  - AIM OF THE STUDY: To report the surgical techniques for multilevel arterial
      lesions of the lower extremities and to evaluate the clinical outcomes. In
      patients with multilevel arterial disease, the treatment consisting of
      sequentially surgical intervention on the same vascular axis is one of the
      methods indicated in order to obtain an adequate inflow and outflow. MATERIAL AND
      METHODS: we have performed a nonrandomized study during a 44-month period
      (January 2010-September 2013) in a number of 58 patients treated by classical
      revascularization techniques. All the patients included in the study have been
      post-surgically surveyed at well-established intervals (1, 3, 6, 9, 12, 24 and 36
      months) by: clinical examination, laboratory tests, Duplex ultrasound, and, as
      needed, CT Angiography. RESULTS: the 6 months primary patency in each studied
      group (corresponding to the years of 2010, 2011 and 2012) was 95%, 93.33%, and
      91.3%, respectively; the 12 months primarypatency was 85%, 80%, and 82.6%,
      respectively. Clinical improvement has been noticed in44 patients (75.86%). There
      have been registered 14 amputations (24.13% of the cases): 7 majors (thigh and
      below the knee), representing 12.06% of the total number of cases and 7 minors
      (toe or transmetatarsal), representing 12.06% of the total number of cases. Limb
      salvage rate for the patients in stage III and IV Leriche-Fontaine was 85.10%.
      CONCLUSIONS: the surgical techniques are a feasible option for the multilevel
      arterial disease, with

PMID- 25581967
TI  - Clinical-epidemiological study on the incidence of postoperative complications
      after pulmonary resection for lung cancer.
AB  - AIM: To determine the relationship between the characteristics of a group of lung
      cancer patients, lung cancer surgeries, and the incidence of early and/or late
      postoperative complications. MATERIAL AND METHODS: The study included a group of
      115 lung cancer patients aged 40 to 85 years, 76.5% men, 60.91% living in urban
      areas, who received surgical treatment in the interval January 2013-August 2014.
      Data were collected from electronic medical records and survey sheets and
      processed and interpreted using Pearson correlation index (p-value of 0.05 was
      considered statistically significant and of <0.005 highly statistically
      significant), and chi2, y, 1c = 25% tests. All statistical analyses were
      performed using the SPSS statistical software package version 13.0. RESULTS: Of
      the 115 patients 7.8% were in the 40-50 years age group and 87.8% in the 51-75
      years age group (p < or = 0.001). Most patients were males (76.5%, p < 0.001),
      and 60.9% of the patients were living in urban areas (p < or = 0.05). The
      difference in the prevalence of smokers (76.5%) vs. non smokers (23.5%) was
      highly statistically significant (p < 0.005). Active smoking of one pack of
      cigarettes per day for more than 10 years was recorded in 54.8%. The presence of
      co morbidities (17 events) and the distribution of neoplastic lesions in the five
      anatomical areas required the performance of lobectomies, bilobectomies or
      pneumectomies. The incidence of early (14 entities) and late postoperative
      complications (7 entities) depended on patient's general condition, nature of co
      morbidities, location and stage of neoplastic lesions, and surgical complexity.
      CONCLUSIONS: Lung cancer, in various locations and stages, most commonly affected
      males aged 40-85 years, from urban areas, smokers, with various co morbidities.
      Surgeries performed in these patients were often laborious and with a relatively
      low incidence of postoperative complications.

PMID- 25581968
TI  - Improved experimental burn model on rabbits.
AB  - OBJECTIVE: The goal of our study was to find an easy and suitable skin burn model
      for rabbits, to identify the temperature and contact time to reach a deep 2nd
      degree burn, and to find the best wound dressing fixation method. MATERIAL AND
      METHODS: We used New Zealand male rabbits as experimental models. On a pilot
      study, with a copper device heated to temperatures between 43-48 Celsius degrees,
      the burn was inflicted using contact timesof 3, 4, 5, and 7 seconds. The burn
      depth was evaluated histological. Twenty-four rabbits were used to evaluate four
      dressing fixation methods: regular dressing with retention bandages; skin
      stapler; collars and body resin cast. RESULTS: A 2nd degree deep burn was
      obtained at 43 degrees for 4 seconds. The retention elastic bandages were removed
      within hours and the skin staplers were removed with teeth leaving wounds on the
      skin. The collars were more successful but produced superficial neck lesions. The
      body resin casts were the most successful. CONCLUSIONS: The best contention
      method was the bpdy resin cast.

PMID- 25581970
TI  - Multifactorial analysis of local and lymph node recurrences after conservative or
      radical surgery for stage 0-II breast cancer.
AB  - AIM: Multifactorial analysis of local and lymph node recurrences in stage 0-II
      breast cancer treated by conservative or radical surgery. MATERIAL AND METHODS:
      In the interval January 1, 2005-July 31, 2013, 477 breast cancer patients were
      assessed by imaging techniques at the Radiology Clinic of Iasi "Sf. Spiridon"
      Hospital and Radiology Service of the Iasi Regional Cancer Institute. Of these
      229 (48%) patients underwent conservative surgery and 248 (52%) patients radical
      surgery. RESULTS: Local recurrences were 2.8 times more frequent in
      conservatively vs. radically treated patients, and lymph node recurrences 2 times
      more frequent in patients treated conservatively. Breast tumors larger than 3 cm
      in diameter were at higher risk for local and distant recurrence in lymph nodes.
      CONCLUSIONS: Assessment in patients with local and lymph nodes recurrences of the
      relative risk for developing other types of recurrences (bone, pleuro pulmonary,
      liver, brain metastases) indicated that these are a risk factor for other types
      of recurrences, influencing the prognosis of patients. Local recurrences showed a
      higher relative risk for other types of recurrences than nodal recurrences.

PMID- 25581969
TI  - Aortocoronary bypass graft patency assessed by coronary computed tomography
      angiography--unicentric study.
AB  - Coronary artery bypass graft (CABG) surgery is used to revascularize ischemic
      myocaydium affected by coronary artery obstruction. Conventional coronary
      angiography (CCA) is an invasive method used for graft evaluation. Nowadays, in
      post CABG patients grafts can be assessed noninvasively by using coronary
      computed tomography angiography (CCTA). AIM: To determine the late patency rate
      in coronary bypass grafts using CCTA. METHODS: To assess graft patency, sixty
      post CABG patients (51/60 males and 9/60 females) were evaluated using dual
      source computed tomography (DSCT) angiography. All patients underwent a primary
      isolated CABG surgery between January 2000 and December 2004, performed by a
      single surgeon, at the Dartment of Cardiovascular Surgery, "Prof. Dr. George I.
      M. Georgescu" Institute for Cardiovascular Diseases, Iasi, Romania. The grafts
      were classified as patent, occluded and stenotic (stenosis >50%). RESULTS: The
      mean age of patients was 68.05-7.59 years and the mean time after graft
      implantation was 129.53-16.74 months. The number of assessed grafts was 200,
      including 146 saphenous vein grafts (SVG) and 54 in situ left internal mammary
      artery (LIMA) grafts. A total number of 105/146 (71.92%) venous grafts and 52/54
      (96.3%) arterial grafts were patent. CONCLUSION: Nowadays, computed tomography
      angiography is a modern noninvasive imaging modality used to evaluate the
      aortocoronary graft patency in early and late postoperative settings. In our
      study, the late saphenous graft patency rate was superior to that found in
      earlier angiographic studies.

PMID- 25581971
TI  - The influence of deltalycyn and transcranial cerebellar stimulation upon recovery
      of retina after photo stress in patients with diabetic retinopathy.
AB  - AIM: The characteristics of visual evoked potentials (VEP) have been studied in
      diabetic patients with and without diabetic retinopathy. MATERIAL AND METHODS:
      Magnetic impulses (2.0 T1 at the height of impulse) have been delivered to the
      cerebellar surface transcranially using the "Neuro-MS/D", (Russia Federation).
      Delta- sleep inducing peptide ("Deltalycyn", "Biopharma", Russia Federation) was
      intranasally delivered in 30 min before photostress. Afterwards VEP have been
      registered every 20 s from the moment of photo stress during one minute. RESULTS:
      An increase of the latency period and a reduction of the VEP amplitude have been
      recorded in the period following photo stress exposure of the macular part of the
      retina. The VEP characteristics restored to the initial level in 73.5 +/- 3.3 s
      from the photo stress moment in the control group; while in diabetic patients
      with retinopathy this index was 137.2 +/- 11.3 s. In the. presence of cerebellar
      transcranial magnetic stimulations (2.0 T1, 20 impulses) the VEP amplitude
      depression was less pro- nounced, and the restoration period of the VEP
      characteristics shortened to 110.3+ 12.7 s, while in deltalycyn treated patients
      restoration was observed in 95.1+ 6.8 s. Under condition of combined usage of
      deltalycyn and TMS period of restoration of VEP was shortened up to 82.5 +/- 6.5
      s. CONCLUSIONS: Retinopathy development is linked to prolonged VEP latency period
      (P100), lowering of the N75-P100 amplitude, as well as to enlargement of the
      recovery period of the retina's functional capacity in patients suffering from
      the diabetes mellitus in the presence of photo stress. Superlatively administered
      deltalycyn and cerebellar transcranial magnetic stimulation facilitates a faster
      recovery of the retina's functional capacity in response to photo stress in
      diabetic patients with retinopathy. 3. Combined usage of deltalycyn and
      cerebellar transcranial stimulation caused the potentiated shortening of post
      photo stress recovering of VEP in patients with diabetic retinopathy.

PMID- 25581972
TI  - Fanconi anemia with cleft palate.
AB  - Fanconi anemia (FA) is a rare plurimalformative syndrome (1/350,000 newborns)
      presenting a large phenotypic heterogeneity, chromosomal instability and
      autosomal recessive inheritance (OMIM 227650). CASE PRESENTATION: Male patient
      followed in the genetics service since infancy, till death. The child was
      referred for multiple congenital anomalies: bilateral aplasia of the radius and
      thumb, left kidney agenesis, cardiac malformation cleft palate, bilateral
      cryptorchidism, ear anomalies, which were associated, in time, with facial
      hyperpigmentation, anomalies of dental eruption, nasal septum deviation, and
      lumbar scoliosis. By the age of 10 years, he develop progressive pancytopenia,
      aplastic anemia. The diagnosis was completed by medulogram, immunogram, and
      karyotype. Treatment was primarily hematologic with substitution products,
      immunosuppressive, marrow stimulants, antibiotic therapy. Death occurred at age
      of 16 by infection and pulmonary hemorrhage occurred in severe pancytopenia.
      CONCLUSIONS: It is presented a rare case of Fanconi anemia customized by the
      clinical association with cleft palate and instructive clinical and evolutionary
      complexity.

PMID- 25581973
TI  - Ethical views, attitudes and reactions of Romanian medical students to the
      dissecting room.
AB  - AIM: Our objective was to evaluate the attitudes and views of first year medical
      students towards cadaver dissection in anatomy learning and discuss various
      findings in relation with ethical problems). MATERIAL AND METHOD: The study was
      conducted at the "Iuliu Hat ieganu" University of Medicine and Pharmacy, during
      the academic year 2012-2013 at the end of the second semester. There were 121
      first year medical students included. We developed a questionnaire to asses among
      other, the degree of fear, anxiety and stress in the dissection room, methods of
      coping, ethical aspects of dissection and hand it to the students. RESULTS: 34.7%
      of students experienced different levels of fear on exposure to the dissection
      room practical sessions. Many students experienced anxiety in reaction to
      dissection. In the first semester most students reported physical and behavioral
      reaction towards certain stimuli, with a decrease in the second semester.
      Recurring visual images of cadavers, reported by 57% of students in the first
      semester, dropped to 44.6% in the second semester. Students used most frequently
      the "rationalization and emotional detachment" as a coping method. CONCLUSIONS:
      Anatomists, most often the firsts who need to be aware of emotional and ethical
      issues, need to explain in detail the steps necessary for dissection and that
      dissection is performed with the respect of legislation, ethics and human rights.

PMID- 25581974
TI  - Descriptive study on acute gastroenteritis in 3,883 patients admitted in "sf.
      Maria" children hospital from Iasi, Romania, between 2008 and 2013.
AB  - The aim of study was to assess some population characteristics in children of
      acute gastroenteritis (AGE) admitted in a regional pediatric hospital. MATERIAL
      AND METHODS: For the present transversal descriptive study we considered a group
      of subjects hospitalized for AGE in 2008-2013 (2013--only 6 months) in "Sf.
      Maria" Emergency Hospital for Children Iasi, Romania. Consultations in the
      Emergency Unit of this hospital did not take into consideration. RESULTS: Number
      of AGE cases admitted to "St. Maria" Emergency Hospital for Children Iasi between
      2008 and 2013 has seen a steady decline. Male subjects are better represented
      (54.1%); largest age group 1-4 years, with 1,827 cases, immediately followed by
      group 0-1 year (1789 cases); together, the two-age groups account for 93.1% of
      admissions for AGE. Distribution of cases by seasons showed balanced values, with
      higher percentages in summer (29.7%) and spring (25.5%). The number of cases is
      relatively constant and lower in winter, affecting predominantly younger groups
      (0-5 years) compared to the summer when cases aged 5 to 14 years were admitted
      more frequent. Most cases presented at admission vomiting (41.2%) and fever
      (40.7%); the presence of bacterial flora was identified in 82.2% of stool
      specimens, and blood in 13.4% of cases. CONCLUSIONS: A higher number of education
      measures should be implemented in urban and rural areas in order todecrease the
      contamination with pathogenic agents involved in infectious acute gas-
      troenteritis in children.

PMID- 25581975
TI  - Is it enough scintigraphy for everyone? A cross-sectional analysis regarding the
      impact of justice in the distribution of health care resources.
AB  - AIMS: The aim of this study was to evaluate the influence of three demographic
      criteria: gender, age and education level on the patients that perform a
      scintigraphy. MATERIALS AND METHODS: The cross-sectional study was applied to 220
      patients to whom it was prescribed a scintigraphy by their treating physician. Of
      these, 74 were men and 145 women, 10 children and 210 adults. According to their
      education, 88 people did not graduate a high school, a total of 56 people
      graduated a high school, 27 persons graduated a college, 22 people had a
      university diploma and 26 people a PhD title. The chi-square test was used to
      analyze the frequencies for the measurable variables on a nominal scale. The
      significance threshold is considered to be 0.05, so, only the values which are
      smaller were taken into consideration. We presented and analyzed only the data
      that fulfill this condition. RESULTS AND DISCUSSION: From our study it has been
      found that gender criterion played an important role in performing a scintigraphy
      for the first time. 71.6% of male patients were undergoing a scintigraphy for the
      first time. The frequency of exploration by scintigraphy is increasing if you are
      a female patient than if you are a male patient: chi-square calculated value is
      chi2 (3)=12.398, p=0.006. From our study it has been found that age item plays an
      important role in the scintigraphy investigations for all the patients. The first
      scintigraphy was significantly performed in the 40-50 years old gap, whilst for
      the patients being aged over 60; they were probably not performing a first time
      scintigraphy. We did not find significant statistical differences in respect of
      the education level. CONCLUSIONS: So, we can conclude that access to that medical
      investigation is not depending on the socioeconomic status of the patient, but in
      some occasions, the number and the frequency distribution of performing a
      scintigraphy depend on gender and age. We can also conclude that the principle of
      egalitarianism is fulfilled and so the justice principle in the distribution of
      health care resources must be reevaluated.

PMID- 25581976
TI  - Epidemiology and pathology of parotid tumors five-year retrospective study.
AB  - AIM: To retrospectively analyze the epidemiological, clinical and pathological
      data of parotid tumors. MATERIAL AND METHODS: Reassessment of the histologic
      diagnosis of parotid tumor in the patients admitted to the Oral and Maxillofacial
      Surgery Unit of the Iasi "Sf. Spiridon" University Emergency Hospital during 2009
      2013. Data on gender, age, place of residence, location, size, surgical procedure
      type and histopatological type were recorded. RESULTS: The risk of developing
      pleomorphic adenonma is 7.40 times higher in women and 4.08 times higher before
      the age of 50 years. The risk of Warthin tumor is 16.47 times higher in male
      patients and 3.58 times higher in urban patients. People older than 50 years have
      a 7.14 times higher risk of developing malignancy and rural people have a 2.41
      times higher risk of developing cancer. Diabetes, obesity and systemic
      hypertension were not important risk factors in our study. CONCLUSIONS: According
      to this study age and the place of residence could be important predictors for
      parotid gland tumors. Since in Romania there are few epidemiological data
      regarding the parotid gland pathology, further cohort studies are needed for a
      better understanding of their clinical and pathological behavior.

PMID- 25581977
TI  - A possibility to identify the vehicle driver through complex forensic and
      criminalistic expertise--case report.
AB  - Traffic accidents can have more or less dramatic consequences that involve penal
      and civil responsibility with amplitude extending over long periods of time. In
      many cases, substitution of the driver with the passenger in order to avoid
      criminal responsibility is often remarked. The substitution takes place with the
      passenger's agreement or, in cases with dramatic consequences (coma or death),
      without his/her consent. These situations are encountered in civil cases
      regarding insurance fraud. In addition to forensic medical expertise, to aid the
      experts, mathematical modeling and computer simulation of the dynamics of vehicle
      passengers is a tool that completes the criminal expertise of traffic accidents.
      This paper presents the method of identification of the person driving the
      vehicle based on the computer simulation of vehicle occupants' dynamics.

PMID- 25581978
TI  - Maxillary sinus anatomic and pathologic CT findings in edentulous patients
      scheduled for sinus augmentation.
AB  - OBJECTIVES: An aberrant sinus anatomy or pathology can influence the sinus lift
      technique if it is encountered during surgical exposure. The purpose of the
      present study was to determine the prevalence of sinus disease and variations of
      normal anatomy among edentulous patients prior to sinus augmentation. MATERIAL
      AND METHODS: 120 patients attending a private surgical practice (53 women and 67
      men, with a mean age of 62.02 years, ranging between 34 and 81 years old) for
      whom treatment was planned for sinus augmentation were evaluated--medical
      history, radiographic and clinical examinations. Computerized tomograms (CT) and
      3D reconstructions from 240 sinuses were analyzed using Dental CT. RESULTS:
      Abnormalities were diagnosed in 74.2% of cases. Mucosal thickening was the most
      prevalent abnormality (68.3%), followed by retention cysts (15.8%) and
      opacification (9.2%). The diagnosed conditions included mucosal thickening,
      chronic sinusitis, sinus cysts and polyps. The prevalence of one or more septa
      per sinus was found to be 30%. Males present pathology more often than females
      (p=.028). No statistical correlation could be found between age and pathology
      (p>0.05) No significant differences in age or gender between patients with and
      without sinus septum were found (p>0.05). CONCLUSIONS: The results reinforce the
      importance of thorough history taking and clinical and radiographic assessment
      prior to performing sinus augmentation, to prevent the probability of
      complications.

PMID- 25581980
TI  - Microparticulate drug delivery system containing tramadol hydrochloride for pain
      treatment.
AB  - The current trend of replacing conventional pharmaceutical forms is justified
      because most substances administered in this form give fluctuations of
      therapeutic concentrations and often outside the therapeutic range. In addition,
      these formulations offer a reduction in the dose or the number of
      administrations, thus increasing patient compliance. AIM: In the experiment, we
      developed an appropriate technology for the preparation of gelatin microspheres
      containing tramadol hydrochloride by emulsification/cross-linking method.
      MATERIALS AND METHODS: The formulated microspheres were characterized by product
      yield, size distribution, encapsulation efficiency and in vitro release of
      tramadol hydrochloride. Data obtained from in vitro release studies were fitted
      to various mathematical models to elucidate the transport mechanisms. The kinetic
      models used were zero-order, first-order, Higuchi Korsmeyer-Peppas and
      Hopfenberg. RESULTS: Spherical microspheres were obtained, with free-flowing
      properties. The entrapment efficiency of tramadol hydrochloride in microparticles
      was 79.91% and product yield -94.92%. As the microsphere size was increased, the
      entrapment efficiency increased. This was 67.56, 70.03, 79.91% for formulations
      MT80-250, MT8-500 and, MT250-500. High entrapment efficiency was observed for
      MT250-500 formulation. The gelatin microspheres had particle sizes ranging from
      80 to 500 microm. The drug was released for a period of 12 hours with a maximum
      release of 96.02%. Of the three proposed formulations, MT250-500 presented
      desirable properties and optimal characteristics for the therapy of pain. Release
      of tramadol hydrochloridi was best fitted to Korsmeyer-Peppas equation because
      the Akaike Information Criterion had the lowest values for this kinetic model.
      CONCLUSIONS: These results suggest the opportunity to influence the therapeutic
      characteristics of gelatin microspheres to obtain a suitable drug delivery system
      for the oral administration of tramadol hydrochloride.

PMID- 25581979
TI  - Spatter contamination in dental practices--how can it be prevented?
AB  - Infectious diseases endanger all dental personnel during treatment, especially
      when spatter and aerosols are produced. Therefore, there is a strong need for
      better infection control principles during all treatments. The purpose of this in
      vitro pilot study was to measure the environmental spatter contamination through
      a fluorescence technique. Scaling was performed using different power-driven
      devices and high-volume evacuation combined with a newly developed cannula (PS),
      standard suction cannulas (STS) and saliva ejectors (CDS). MATERIAL AND METHODS:
      One sonic (AIR) and two ultrasonic devices (TIG, VEC) were utilized to remove
      biofilm from 168 artificial teeth in a manikin head. Teeth were scaled for 120s
      supra- or subgingivally. The spatter contamination of an area of 1.5m2 around the
      manikin head was assessed. RESULTS AND CONCLUSIONS: The contaminated area (%) was
      significantly different for the AIR (median [25th; 75th percentiles]: 2.5 [1.16;
      6.05]) versus TIG (0.25 [0.18; 0.88]) and VEC (0.08 [0.06; 0.1]) (p<0.001).
      Irrespective of the instrument, subgingival scaling led to a less contaminated
      area (0.18 [0.07; 1.05]) than supragingival scaling (0.34 [0.1; 2.24]) (p <
      0.001). High-volume evacuation combined with STS (0.17 [0.07; 1.04]) and PS (0.18
      [0.07; 1.14]) reduced the contamination similarly (p=0.302) and was more
      effective compared to CDS (1.01 [0.12-5.78]) (p<0.001; p=0.002). Beside the
      limitation of an in-vitro investigation, it can be conclude that only high-volume
      evacuation with an adequately calibrated cannula is capable of significantly
      reducing the amount of spatter contamination produced during power-driven
      scaling.

PMID- 25581981
TI  - Development of a modified-release pellets formulation--with metoprolol tartrat
      and kinetic aspects of in vitro release.
AB  - AIM: The development of a new pellets formulation which is able to modulate the
      release of metoprolol tartrate, an active pharmaceutical ingredient very soluble
      in water and therefore very difficult to process. MATERIALS AND METHODS: Two
      types of different viscosity grade hydroxypropyl methylcellulose (Methocel K100;
      HPMC 15.000) and Eudragit NE30D are used as prolonged drug release agents, thus
      resulting in three formulations which have been prepared in form of pellets, in a
      conventional coating pan. The obtained pellets are characterized and compared in
      terms of: particles size distribution, drug loading efficiency, drug content and
      kinetic of in vitro drug release. RESULTS: Lower amounts of Eudragit NE30D (7.5%)
      determine more uniform size distributions of particles. Drug content and charging
      efficiency is higher in case of fractions ranging in size from 0.80 to 1.25 mm.
      The combination of HPMC 15000 with 10% Eudragit NE30D leads to a prolongation for
      a period of 11.5 hours of metoprolol tartrate release. Release kinetics analysis
      was performed by fitting the in vitro release profile with different kinetic
      models. CONCLUSIONS: It was developed a pellets formulation that release in vitro
      the metoprolol tartrate in an extended mode, with Korsmeyer-Peppas kinetic-type.

PMID- 25581982
TI  - New hydrazones of ferulic acid: synthesis, characterization and biological
      activity.
AB  - The ferulic acid (4-hydroxy-3-methoxy-cinnamic acid) is a phenolic compound with
      important antioxidant effects and which nowadays is being extensively studied for
      his potential indications in inflammatory and neurodegenerative diseases,
      hypertension, atherosclerosis, etc. AIM: The synthesis of new ferulic acid
      compounds with potential antioxidant activity. MATERIAL AND METHODS: The
      synthesis of the designed compounds was performed in several steps: (i) the
      obtaining of ferulic acid chloride by reacting of ferulic acid with thionyl
      chloride; (ii) the reaction between the ferulic acid chloride and hydrazine
      hydrate 98% to obtain the ferulic acid hydrazide; (iii) the condensation of
      ferrulic acid hydrazide with various benzaldehydes (2-hydroxy/3-hydroxy/4
      hydroxy/2-nitro/3-nitro/4-nitro/2-methoxi/ 4-chloro/4-fluoro/4-bromo
      benzaldehyde) resulting the correspond- ing hydrazones. RESULTS: The structure of
      the synthesized compounds was confirmed by FT-IR spectroscopy and the evaluation
      of antioxidant potential was achieved by determining the total antioxidant
      capacity and reducing power. CONCLUSIONS: In this study new hydrazones of ferulic
      acid have been synthesized, physic-chemical and spectral characterized. The
      evaluation of antioxidant potential using in vitro methods showed the favorable
      influence of the structural modulation on the antioxidant effects of ferulic
      acid.

PMID- 25581983
TI  - In memoriam: Louis E. Underwood, MD (1937- 2014).

PMID- 25581984
TI  - In memoriam: Raymond L. Hintz, MD (1939- 2014).

PMID- 25581985
TI  - Are the new automated methods for bone age estimation advantageous over the
      manual approaches?
AB  - Bone Age Assessment (BAA) is performed worldwide for the evaluation of endocrine,
      genetic and chronic diseases, to monitor response to medical therapy and to
      determine the growth potential of children and adolescents. It is also used for
      consultation in planning orthopedic procedures, for determination of
      chronological age for adopted children, youth sports participation and in
      forensic settings. The main clinical methods for skeletal bone age estimation are
      the Greulich and Pyle (GP) and the Tanner and Whitehouse (TW) methods. Seventy
      six per cent (76%) of radiologists or pediatricians usually use the method of GP,
      20% that of TW and 4% other methods. The advantages of using the TW method, as
      opposed to the GP method, are that it overcomes the subjectivity problem and
      results are more reproducible. However, it is complex and time consuming; for
      this reason its usage is just about 20% on a world-wide scale. Moreover, there
      are some evidences that bone age assignments by different physicians can differ
      significantly. Computerized and Quantitative Ultrasound Technologies (QUS) for
      assessing skeletal maturity have been developed with the aim of reducing many of
      the inconsistencies associated with radiographic investigations. In spite of the
      fact that the volume of automated methods for BAA has increased, the majotity of
      them are still in an early phase of development. QUS is comparable to the GP
      based method, but there is not enough established data yet for the healthy
      population. The Authors wish to stimulate the attention on the accuracy,
      reliability and consistency of BAA and to initiate a debate on manual versus
      automated approaches to enhance our assessment for skeletal matutation in
      children and adolescents.

PMID- 25581986
TI  - Novel long-acting GH preparations.
AB  - BACKGROUND: Growth hormone (GH) treatment currently requires years of treatment.
      Maintaining full compliance with daily injections has been difficult. Teens have
      the highest rate of non-concordance (missing injections 1-2 per week). In adults
      the rate of low concordance (low IGFI) rises with each year of treatment.
      Improving compliance to GH therapy by less burdensome means of GH replacement can
      be achieved either by changing GH delivery frequency (weekly, monthly) or by
      changing injection device characteristics (minimal preparation, easy setting,
      minimal pain, automatic needle insertion, needle free devices). LONG ACTING
      FORMULATIONS: Long-acting forms of GH have been developed either as sustained
      release preparations of GH (Nutropin-depot, which has been withdrawn in 2004 and
      LB 03002 once weekly GH, which has received a positive opinion by CHMP of EMA in
      early 2013) or as the conjugated analogues which prolong the half life of GH.
      Currently a variety of modified GH molecules which delay GH clearance (CTP
      modified GH, recombinant polypeptide XTEN, GH conjugated with albumin, GH linked
      to immunoglobulin) are studied and the ongoing studies are in different phases
      (from I-III). Each of these preparations has been tested in experimental animal
      models. EFFICACY AND SAFETY: Although different types of formulations have been
      studied, all are pharmacokinetically and pharmacodynamically effective in
      extending GH action and result in prolonged increase in IGF-I concentrations.
      Clinical data are available for once-weekly sustained-release GH treatment and
      the data show beneficial effects in adults with GH deficiency over a 12 month
      period and adequate growth rate in pre-pubertal children with GH deficiency over
      the period of three-years. CONCLUSIONS: Clinical data are still very limited.
      Available short-term studies show that treatment with long-acting GH preparation
      is effective and safe in GH deficient children and adults. A different physiology
      underlies the long-acting GH and we still need to improve our knowledge about
      these formulations of GH. Long-term studies are needed to confirm the value and
      safety (greater exposure to GH) of these agents.

PMID- 25581987
TI  - Prevalence of dyslipidemia and metabolic syndrome risk factor in overweight and
      obese children.
AB  - OBJECTIVE: To study the prevalence of dyslipidemia and metabolic syndrome risk
      factors in overweight/ obese children and adolescents. METHODOLOGY: The study
      included 139 healthy white Argentinean children/adolescents (aged 8-14 years) who
      were overweight (n = 30) or obese (n = 109), based on BMI z score according to
      WHO, 2007. Children were referred to the Nutrition Clinic, San Martin University
      Hospital, Buenos Aires, Argentina for evaluation and treatment. Dyslipidemia was
      considered when one or more serum lipids (mg/dL) were out of range: total
      cholesterol >= 200, high-density lipoprotein (HDL-C) <= 40, triglycerides (TG) >
      110, low-density lipoprotein (LDL-C) > 130 or non-HDL-C > 145 and fasting blood
      glucose (FBG) > 110. Additional metabolic syndrome risk factors included:
      increased waist circumference (WC, >= 90th percentile) and high blood pressure (>
      90th percentile). A history of low birth weight (< 2.5 kg) and a family history
      of: dyslipidemia (FHDL), premature acute myocardial infarction (FHPAMI) and/or
      type 2 diabetes mellitus (FHT2DM) were also assessed. RESULTS: The prevalence of
      dyslipidemia among overweight and obese children was 50.4% and its pattern was:
      hypertriglyceridemia 31.9%, low HDL-C 29.7%, high non-HDL-C 15.8%,
      hypercholesterolemia 11.9%, and elevated LDL-C 10.7%. The dyslipidemia was more
      often detected among those with increased WC (55.4%), FHDL (51.1%), and FHT2DM
      (48%); prevalence was lower in those with FHPAMI (18.7%) and low birth weight
      (4.3%). Most children presented a variety of metabolic syndrome risk factors;
      only 25.8% did not have any such alterations identified. BMI z score showed a
      positive association with TG and negative with HDL-C. Overweight and obesity
      increased the odds ratios of metabolic syndrome risk factors,
      hypertriglyceridemia and low HDL-C. CONCLUSIONS: Overweight/obese children were
      prone to have dyslipidemia and metabolic syndrome. Excess body weight is an
      important harbinger of health that requires the assessment of multiple parameters
      to discern further health concerns that may be amenable to specific treatment.

PMID- 25581988
TI  - Nonclassical congenital adrenal hyperplasia: targets of treatment and transition.
AB  - Nonclassical congenital adrenal hyperplasia (NCCAH) caused by 21-hydroxylase
      deficiency is a common autosomal recessive condition that can present with a wide
      range of hyperandrogenemic signs in childhood or adulthood. The management of
      children with NCCAH can be challenging, as no universally accepted guidelines
      have been established. Our goal was to evaluate the literature and develop an
      evidence-based guideline for the medical management of children and adolescents
      with NCCAH. We reviewed the published literature and used the Grading of
      Recommendation, Assessment, Development, and Evaluation (GRADE) system when
      appropriate to grade the evidence and provide recommendations for the medical
      management of children and adolescents with NCCAH, appropriate transition
      practices from pediatric to adult endocrine care, and psychological issues that
      should be addressed in parents and patients with NCCAH. We offer recommendations,
      based on the available evidence, for the management of NCCAH at the different
      developmental stages from diagnosis through transition to adulthood.

PMID- 25581989
TI  - Endocrine Society 96th Annual Meeting & EXPO Chicago, IL USA (June 20-24, 2014)
      selected highlights.

PMID- 25581990
TI  - Worlds of paper: an introduction.

PMID- 25581991
TI  - Ulisse Aldrovandi's Pandechion epistemonicon and the use of paper technology in
      Renaissance natural history.
AB  - Reconstructing the formation and use of the hitherto neglected Pandechion
      epistemonicon, Ulisse Aldrovandi's (152-1605) extant manuscript encyclopaedia,
      this article shows that early modern naturalists in many ways shared a world of
      paper with the members of several other professions. An analysis of the
      Pandechion suggests that Renaissance naturalists who applied the humanist jack-of
      all-trades, the commonplace book, in their own field sometimes considerably
      altered its form. Aldrovandi tested and recombined different techniques so as to
      arrive at the paper technology that he considered to be the most fit for his
      purposes. He thereby drew on administrative practices as well as on the
      bookkeeping practices of early modern merchants that he knew first-hand.

PMID- 25581992
TI  - Nero and the last stalk of Silphion: collecting extinct nature in early modern
      Europe.
AB  - Many studies of early modern natural history focus upon observational, empirical
      techniques. Early moderns also contended with entities which could no longer be
      observed because they no longer existed. Although it is often assumed that
      extinction only emerged as a concept in the eighteenth century, the concept of
      natural loss appeared, often unproblematically, in areas outside natural
      philosophy. A survey of discussions of the extinct plant silphion across Europe
      in the sixteenth and seventeenth centuries shows that the possibility of natural
      loss was well aired. Paper technologies for collecting extinct nature ran
      parallel to investigations of newly found nature, and thus can place the latter
      in a new light. Although ideas of natural mutability often drew on ideas of
      historical or political change rather than philosophical concepts of natural
      constancy, techniques developed for extinct nature, such as the list of lost
      things, remained influential for the research agendas of naturalists.

PMID- 25581993
TI  - John Locke's "new method of making common-place-books": tradition, innovation and
      epistemic effects.
AB  - In 1676, the English physician and philosopher John Locke published a new method
      of commonplacing. He had developed this method and, in particular, a new approach
      to organizing and indexing the entries, in the course of 25 years of personal
      note-taking and it proved quite influential. This paper presents the three major
      approaches to commonplacing as practiced by physicians and other scholars before
      Locke--the systematic or textbook approach, the alphabetical approach and the
      sequential or index-based approach--and it analyzes the ways in which Locke
      himself applied them in his own commonplace books. In comparison with established
      approaches, his new method offered a maximum degree of flexibilitywhile
      facilitating the later retrieval of notes and minimising waste of space and
      paper. Thanks to these features, it was particularly well suited for physicians
      and natural philosophers who were interested in the infinite variety of natural
      particulars rather than in elegant quotes on a very limited set of classical
      topics. In conclusion, the potential epistemic impact of commonplacing on early
      modern medicine and natural philosophy is discussed, in particular its importance
      for contemporary debates about species and disease entities and for the emergence
      of the notion of "facts"!

PMID- 25581994
TI  - Sauvages' paperwork: how disease classification arose from scholarly note-taking.
AB  - What was classification as it first took modern form in the eighteenth century,
      and how did it relate to earlier ways of describing and ordering? We offer new
      answers to these questions by examining medicine rather than botany and by
      reconstructing practice on paper. First among disease classifications was the
      'nosology' of the Montpellier physician Francois Boissier de Sauvages de Lacroix.
      Analysis of his hitherto unstudied notebooks and of the nosology's many editions
      (1731-1772) shows that Boissier de Sauvages broke with earlier physicians'
      humanistic ordering of disease while sustaining the paper practices they had
      used. Scientific method was scholarly method. Classification arose through an
      incomplete break with, and intensified practice of, a past library-based way of
      ordering the described world. A new empiricism of generalizations (species) arose
      out of an older one of particulars (observationes). This happened through the
      rewriting--not the replacement--of the canon of disease knowledge since antiquity
      and its reordering on the printed page.

PMID- 25581995
TI  - Valuable midwives.

PMID- 25581996
TI  - Where has all the midwifery gone?

PMID- 25581997
TI  - Midwives turn out in their thousands to strike for fair pay, in response to
      government intransigence.

PMID- 25581998
TI  - Microbiome film prompts midwives to call for further research into the effects of
      intervention.

PMID- 25581999
TI  - First live birth after womb transplant gives UK women hope of bearing children
      themselves.

PMID- 25582000
TI  - Doppler scans to assess placental competence: lifesaving technique or over
      complicating low-risk pregnancies?

PMID- 25582001
TI  - Improvements needed to care of pregnant women with diabetes, reveals new report
      from audit.

PMID- 25582002
TI  - Court-ordered caesareans.
AB  - Court-ordered caesarean sections are in the news after a number of recent legal
      decisions authorising surgery for women who lack mental capacity to consent. The
      decisions have not always been based on good evidence and they raise serious
      concerns about the protection of the rights of mentally ill women. The authors
      explain the legal process and question the wisdom of recent judgements.

PMID- 25582003
TI  - The impact of litigation on midwives.
AB  - Litigation is rising in maternity care and there is no evidence that it will slow
      down. Advertisements with a 'no win no fee' message encourage people to seek out
      lawyers. It is true that we are becoming an increasingly litigious society and
      claims in maternity care often lead to very high pay-outs. This can be millions
      of pounds for child with cerebral palsy if liability is admitted. Legal processes
      are fascinating but it does not feel like this if you are personally caught up in
      them.

PMID- 25582005
TI  - Resuscitation of a preterm baby boy.

PMID- 25582004
TI  - Maternity support workers and safety in maternity care in England.
AB  - Errors in health care may lead to poor outcomes or even death. In maternity care
      the issue is more acute as most women and babies are healthy--and mistakes can
      have devastating effects. In the last 20 years 'patient' safety in maternity care
      has received significant attention in terms of both policy and research. With few
      exceptions, the resultant publications have been aimed at health service managers
      or registered health professionals. However a substantial section of the
      workforce now consists of support workers who may receive minimal training. This
      article aims to serve as a reminder that everyone is responsible for the safety
      of maternity care, and the learning needs of unregistered care staff require
      attention to strengthen safety defences.

PMID- 25582006
TI  - Who safeguards mothers?
AB  - While routine screening for group B streptococcus is not recommended in the UK,
      women are sometimes coincidentally found to be carrying these bacteria during
      investigations of symptoms in pregnancy. If such women decide to decline
      intravenous antibiotics for themselves in labour, they can seek support from
      midwives in appropriate roles. But once the woman's baby is born, the situation
      changes somewhat, as the legal context changes and the issue of safeguarding may
      be raised. This article considers the issues that arise in such scenarios and
      raises questions about who is there to support women who experience pressure to
      consent to their healthy newborn baby having prophylactic intravenous
      antibiotics.

PMID- 25582007
TI  - 'Midwives' experiences of workplace resilience'.

PMID- 25582008
TI  - Midwifery Basics: Mentorship: 2. Skills to facilitate learning in clinical
      practice.

PMID- 25582009
TI  - Celebrating international day of the midwife: the future of motherhood.

PMID- 25582010
TI  - The evolving role of the research midwife.

PMID- 25582011
TI  - [Ebola: virus, disease, transmission--and preparedness in Finland].
AB  - Ebola virus has been transmitted from its reservoirs to a human at least about
      twenty times, established limited human-to-human transmission chains and caused
      severe generalized infections, often with symptoms involving hemorrhagic fever.
      Of the five viruses belonging to the genus Ebolavirus, four have been described
      to have caused human disease, three of them having caused epidemics (25 to 90%
      mortality). The present epidemic started in December 2013, evidently from a two
      year-old child in Guinea, and spread to the neighboring countries as well. The
      causative agent of the epidemic is a Zaire ebolavirus strain having undergone a
      cross-species transfer. By October 25, 2014, the epidemic has caused 4,912 deaths
      in the epidemic region. The report reviews the background information on the
      virus, disease and its current spread, as well as describes the ebola
      preparedness currently in Finland.

PMID- 25582012
TI  - [Prognostic factors and treatment of diffuse large cell B-cell lymphoma].
AB  - Diffuse large cell B-cell lymphoma (DLBCL) is the most common lymphoma in the
      western world. The most common symptom is lymphadenopathy. General symptoms may
      include a decrease in performance status, loss of weight, fever and night sweats.
      DLBCL is treated with a combination of anthracyclin-based chemotherapy and the
      CD20 antibody rituximab. 70% of the patients can be cured with the combination
      therapy. To date, clinical risk factors remain as the cornerstone of treatment
      decisions and prognosis. Biological prognostic factors and targeted therapies
      are, however, under active research and it is likely that patients will in the
      near future be treated according to risk-adapted and biomarker-driven therapies.

PMID- 25582013
TI  - [Carotid artery stenosis as predictor of the risk of cerebral and cardiac
      infarction].
AB  - Carotid artery stenoses are the cause of approx. 15% of cerebral infarctions
      which are often difficult and prone to recur. Endarterectomy of a carotid artery
      stenosis that has caused disturbances of the cerebral circulation is an effective
      remedy: operating six tight stenoses will prevent one cerebral infarction. One of
      the most promising methods to identify the patients having the highest risk of
      cerebral infarction is noninvasive imaging of the stenosis. Since the detection
      of a significant carotid artery stenosis is predictive of an increased risk of
      cerebral and cardiac infarction, the vascular risk factors should be identified
      on an individual basis and treated effectively. Screening of asymptomatic carotid
      artery stenoses is, however, not yet recommended.

PMID- 25582014
TI  - [Exome sequencing revealed Allan-Herndon-Dudley syndrome underlying multiple
      disabilities].
AB  - Normal function of the thyroid gland is the cornerstone of a child's mental
      development and physical growth. We describe a Finnish family, in which the
      diagnosis of three brothers became clear after investigations that lasted for
      more than 30 years. Two of the sons have already died. DNA analysis of the third
      one, a 16-year-old boy, revealed in exome sequencing of the complete X chromosome
      a mutation in the SLC16A2 gene, i.e. MCT8, coding for a thyroid hormone transport
      protein. Allan-Herndon-Dudley syndrome was thus shown to be the cause of multiple
      disabilities.

PMID- 25582015
TI  - [Prox1 promotes expansion of the colorectal cancer stem cell population to fuel
      tumor growth and ischemia resistance].

PMID- 25582016
TI  - [Coronary heart disease mortality and hormone therapy before and after the
      Women's Health Initiative].

PMID- 25582017
TI  - [Clinical profile and influences on outcomes in patients hospitalized for acute
      pericarditis].

PMID- 25582019
TI  - [Identification and treatment of malnutrition in a hospital patient].
AB  - Malnutrition associated with a disease remains often undiagnosed despite of
      having a frequency 20 to 60% in the developed countries. Malnutrition delays the
      recovery from diseases and operations, and increases complications and mortality.
      In Europe, the costs caused by malnutrition are two times higher than those due
      to overweight. Good clinical nutritional therapy requires immediate
      identification of patients having or being at risk of malnutrition. Approximately
      one out of three hospital patients is a high-risk patient. Attempts should be
      made to start the clinical nutritional therapy for these patients as early as
      possible.

PMID- 25582020
TI  - [Indications and execution of enteral nutrition].
AB  - Enteral nutrition refers to the administration of nutritional supplements or tube
      feeding into the gastrointestinal tract. It is important to recognize a patient
      who is undernourished or at risk of developing malnutrition. The most common
      indication of tube feeding is dysphagia caused either by a neurologic or a
      mechanical problem, whereas contraindications include acute problems of the
      gastrointestinal tract, e.g. obstruction or perforation of the bowel, or
      abdominal compartment syndrome before a corrective procedure. Tube feeding of a
      longer duration can be performed directly through the abdominal wall with a tube
      inserted endoscopically into the gastrointestinal tract. Tube feeding is started
      moderately and planned according to the patient's nutritional and fluid
      requirement.

PMID- 25582021
TI  - [Improved treatment options for a short bowel syndrome patient].
AB  - Short bowel syndrome necessitates long-term parenteral nutrition, which exposes
      to decreased quality of life and increased morbidity. In recent years the
      understanding of short bowel pathophysiology and related complications has
      expanded, forming the basis for improved treatment options. In addition to
      evolving nutritional therapy, new pharmacological and surgical therapies have
      emerged, enhancing the patients' possibilities to achieve intestinal autonomy.
      Increasingly efficient prevention of intestinal failure-associated liver disease
      and central line-associated septic episodes improves patient survival. Bowel
      function can be restored by intestinal transplantation in those developing life
      threatening complications.

PMID- 25582022
TI  - [Nutrition of a diseased child].
AB  - The objective of nutritional therapy of a child patient is to secure the child's
      normal growth and development. In general, it is possible to achieve the goals by
      using enteral nutrition. Brief parenteral nutrition is often necessary, for
      example after surgical operations. Short-bowel syndrome is one of the diseases
      requiring prolonged parenteral nutrition and presenting exceptionally strong
      challenges for nutritional therapy. The planning and responsibility for
      implementation of nutritional therapy of a severely diseased child belong to
      specialized care. The nutrition team comprises a nutritional therapist, a
      pediatric nurse and a pediatrician specialized in nutrition.

PMID- 25582023
TI  - [Parenteral nutrition--temporary and permanent treatment].
AB  - Enteral nutrition of an elderly patient having ended up in hospital or intensive
      care and suffering from malnutrition should be started as soon as it is
      technically possible. If less than 60% of the estimated energy need is fulfilled
      during the first week of treatment, parenteral nutrition should also be
      initiated. Multi-chamber bags are the most effective means to provide energy and
      nutrients via the central vein. To reduce the risk of liver damage, parenteral
      nutrition is upon prolongation recommended to be administered periodically.
      Weight monitoring is important in order to observe the effect of the treatment
      and the possible accumulation of fluid load.

PMID- 25582025
TI  - Treating cancer with sonodynamic therapy: a review.
AB  - Sonodynamic therapy (SDT) has emerged as a promising option for the minimally
      invasive treatment of solid cancerous tumours. SDT requires the combination of
      three distinct components: a sensitising drug, ultrasound, and molecular oxygen.
      Individually, these components are non-toxic but when combined together generate
      cytotoxic reactive oxygen species (ROS). The major advantage of SDT over its
      close relative photodynamic therapy (PDT), is the increased penetration of
      ultrasound through mammalian tissue compared to light. As a result, SDT can be
      used to treat a wider array of deeper and less accessible tumours than PDT. In
      this article, we critically review the current literature on SDT and discuss
      strategies that have been developed in combination with SDT to enhance the
      therapeutic outcome. 

PMID- 25582024
TI  - Palladium-catalyzed alpha-arylation of aryl acetic acid derivatives via dienolate
      intermediates with aryl chlorides and bromides.
AB  - To date, examples of alpha-arylation of carboxylic acids remain scarce. Using a
      deprotonative cross-coupling process (DCCP), a method for palladium-catalyzed
      gamma-arylation of aryl acetic acids with aryl halides has been developed. This
      protocol is applicable to a wide range of aryl bromides and chlorides. A
      procedure for the palladium-catalyzed alpha-arylation of styryl acetic acids is
      also described. 

PMID- 25582027
TI  - Our knowledge of the world is often not simple: policymakers should not duck that
      fact, but should deal with it.

PMID- 25582030
TI  - Young adults' experiences of living with recessive limb-girdle muscular dystrophy
      from a salutogenic orientation: an interview study.
AB  - PURPOSE: To describe young adults' experiences of living with recessive limb
      girdle muscular dystrophy (LGMD2) from a salutogenic orientation. METHODS: A
      qualitative explorative interview study, including 14 participants aged 20-30
      years, was performed focusing on comprehensibility, manageability and
      meaningfulness in daily life. Content analysis was used for data analysis.
      RESULT: Living with LGMD2 not only implies learning to live with the disease and
      the variations between good and bad periods but also means trying to make sense
      of a progressive disease that brings uncertainty about future health, by striving
      to make the best of the situation. Disease progression involves practical and
      mental struggle, trying to maintain control over one's life despite vanished
      physical functions that require continual adjustments to the body. Restrictions
      in a double sense were described, not only due to the disease but also due to
      poor comprehension of the disease in society. Lack of knowledge about LGMD2 among
      professionals often results in having to fight for the support needed.
      CONCLUSION: In order to manage daily life, it is important to be seen and
      understood as an individual in contacts with professionals and in society in
      general, to have informal social support and meaningful activities as well as
      access to personal assistance if necessary. IMPLICATIONS FOR REHABILITATION:
      Recessive limb-girdle muscular dystrophy (LGMD2) is a group of progressive
      disorders, which manifest in physical and psychological consequences for the
      individual. According to the salutogenic orientation, people need to find life
      comprehensible, manageable and meaningful, i.e. to achieve a sense of coherence
      (SOC), but living with LGMD2 may recurrently challenge the individual's SOC.
      Through the holistic view of the individual's situation that the salutogenic
      orientation provides, professionals may support the individual to strengthen SOC
      and thereby facilitate the movement towards health.

PMID- 25582026
TI  - Dehydrozingerone exerts beneficial metabolic effects in high-fat diet-induced
      obese mice via AMPK activation in skeletal muscle.
AB  - Dehydrozingerone (DHZ) exerts beneficial effects on human health; however, its
      mechanism of action remains unclear. Here, we found that DHZ suppressed high-fat
      diet-induced weight gain, lipid accumulation and hyperglycaemia in C57BL/6 mice
      and increased AMP-activated protein kinase (AMPK) phosphorylation and stimulated
      glucose uptake in C2C12 skeletal muscle cells. DHZ activated p38 mitogen
      activated protein kinase (MAPK) signalling in an AMPK-dependent manner.
      Inhibiting AMPK or p38 MAPK blocked DHZ-induced glucose uptake. DHZ increased
      GLUT4 (major transporter for glucose uptake) expression in skeletal muscle.
      Glucose clearance and insulin-induced glucose uptake increased in DHZ-fed
      animals, suggesting that DHZ increases systemic insulin sensitivity in vivo.
      Thus, the beneficial health effects of DHZ could possibly be explained by its
      ability to activate the AMPK pathway in skeletal muscle. 

PMID- 25582031
TI  - Ease of intravenous catheterisation in dogs and cats: a comparative study of two
      peripheral catheters.
AB  - OBJECTIVES: To evaluate animal comfort and ease of placement of a veterinary
      specific intravenous catheter compared with a catheter manufactured for human
      use. METHODS: Fifty-nine veterinary undergraduates were recruited to perform
      intravenous catheterisations with two brands of over-the-needle catheter [Smiths
      Medical Jelco(r) (human use) and Abbott Animal Health catheter(r) (veterinary
      use)] in 69 healthy cats (n = 28) and dogs (n = 41) requiring general
      anaesthesia. After a standardised pre-anaesthetic medication, each animal was
      randomly allocated to have one of the two brands of catheter placed. Each student
      was allowed a maximum of three attempts to achieve cephalic vein catheterisation.
      The student and a single experienced observer evaluated each attempt.
      Observations related to ease of placement and to the animal's reaction were
      recorded. RESULTS: Human use catheters were placed in 34 and veterinary use in 35
      animals. There was no difference in weight, sex or sedation score between the two
      groups. The number of failed attempts was similar between the two groups. There
      was no difference between groups for the number of animals reacting to catheter
      insertion. CLINICAL SIGNIFICANCE: The two types of catheters evaluated are
      equally suitable for intravenous catheterisation of sedated animals by veterinary
      undergraduate students.

PMID- 25582032
TI  - Multiple myeloma: is a shift toward continuous therapy needed to move forward?
AB  - Multiple myeloma (MM) accounts for 1% of all cancers and 13% of all hematologic
      malignancies. Melphalan-prednisone plus melphalan-prednisone-thalidomide or
      melphalan-prednisone-bortezomib are considered the standards of care for newly
      diagnosed, transplant-ineligible patients with MM (older than 65 years). In newly
      diagnosed, transplant-eligible patients with MM (younger than 65 years), a novel
      agent-based induction followed by high-dose therapy and autologous stem cell
      transplantation, is the standard approach. The availability of novel agents has
      considerably increased the treatment options of this disease, but almost all
      patients relapse after achieving a maximal response to first-line therapy. New
      drugs and new treatment approaches are urgently needed to improve outcome in MM
      patients Continuous therapy can be a valid option to keep the patient symptom
      free and to prolong progression-free survival and overall survival. 

PMID- 25582033
TI  - Natural products as photoprotection.
AB  - The rise in solar ultraviolet radiation on the earth's surface has led to a
      depletion of stratospheric ozone over recent decades, thus accelerating the need
      to protect human skin against the harmful effects of UV radiation such as
      erythema, edema, hyperpigmentation, photoaging, and skin cancer. There are many
      different ways to protect skin against UV radiation's harmful effects. The most
      popular way to reduce the amount of UV radiation penetrating the skin is topical
      application of sunscreen products that contain UV absorbing or reflecting active
      molecules. Based on their protection mechanism, the active molecules in
      sunscreens are broadly divided into inorganic and organic agents. Inorganic
      sunscreens reflect and scatter UV and visible radiation, while organic sunscreens
      absorb UV radiation and then re-emit energy as heat or light. These synthetic
      molecules have limited concentration according to regulation concern. Several
      natural compounds with UV absorption property have been used to substitute for or
      to reduce the quantity of synthetic sunscreen agents. In addition to UV
      absorption property, most natural compounds were found to act as antioxidants,
      anti-inflammatory, and immunomodulatory agents, which provide further protection
      against the damaging effects of UV radiation exposure. Compounds derived from
      natural sources have gained considerable attention for use in sunscreen products
      and have bolstered the market trend toward natural cosmetics. This adds to the
      importance of there being a wide selection of active molecules in sunscreen
      formulations. This paper summarizes a number of natural products derived from
      propolis, plants, algae, and lichens that have shown potential photoprotection
      properties against UV radiation exposure-induced skin damage. 

PMID- 25582034
TI  - Long-term outcome after early repair of iatrogenic bile duct injury. A national
      Danish multicentre study.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate the peri
      operative and long-term outcome after early repair with a hepaticojejunostomy
      (HJ). METHODS: Between 1995 and 2010, a nationwide, retrospective multi-centre
      study was conducted. All iatrogenic bile duct injury (BDI) sustained during a
      cholecystectomy and repaired with HJ in the five Hepato-Pancreatico-Biliary
      centres in Denmark were included. RESULTS: In total, 139 patients had an HJ
      repair. The median time from the BDI to reconstruction was 5 days. A concomitant
      vascular injury was identified in 26 cases (19%). Post-operative morbidity was
      36% and mortality was 4%. Forty-two patients (30%) had a stricture of the HJ. The
      median follow-up time without stricture was 102 months. Nineteen out of the 42
      patients with post-reconstruction biliary strictures had a re-HJ. Twenty-three
      patients were managed with percutaneous transhepatic cholangiography and
      dilation. The overall success rate of re-establishing the biliodigestive flow
      approached 93%. No association was found between timing of repair, concomitant
      vascular injury, level of injury and stricture formation. CONCLUSION: In this
      national, unselected and consecutive cohort of patients with BDI repaired by
      early HJ we found a considerable risk of long-term complications (e.g. 30%
      stricture rate) and mortality in both the short- and the long-term perspective.

PMID- 25582035
TI  - A special healing pattern in stable metaphyseal fractures.
AB  - BACKGROUND AND PURPOSE: Metaphyseal fractures heal in a rapid fashion that is
      different from the bone shaft healing process. Animal studies have focused on
      diaphyseal fractures. We investigated the metaphyseal fracture-healing process in
      rabbits. ANIMALS AND METHODS: 60 rabbits (divided into 12 groups) underwent
      proximal tibial osteotomy, anatomical reduction, and fixation with screws. After
      surgery, the proximal tibiae were harvested at different time points for
      histology. RESULTS: No obvious osteonecrosis or bone resorption were found 2
      weeks after surgery. From day 5 to week 5, woven bone or new trabeculae formed.
      From week 2, remodeling into lamellar bone started and reached a peak at week 6.
      These 3 stages overlapped. Histomorphometry showed that the structure changed as
      a unimodal curve. INTERPRETATION: The healing process of metaphyseal fractures
      appears to differ from the commonly studied healing process in diaphyseal
      fractures. It is rapid, and can be divided into 4 histological stages: cellular
      activation and differentiation, formation of woven bone, transformation of woven
      bone into lamellar bone, and further remodeling.

PMID- 25582036
TI  - A multicenter analysis of clinical hemolysis in patients supported with durable,
      long-term left ventricular assist device therapy.
AB  - BACKGROUND: Despite the beneficial effects of mechanical circulatory support
      (MCS), the majority of patients ultimately will have an adverse event. Although
      hemolysis is common among temporary devices, the incidence and clinical
      significance of hemolysis in patients managed with long-term, durable left
      ventricular assist device (LVAD) therapy is largely unknown. METHODS: Data were
      obtained from the Interagency Registry for Mechanically Assisted Circulatory
      Support (INTERMACS). All adults who received a continuous-flow LVAD (CF-LVAD)
      between June 2006 and March 2012 were included. A hemolytic event was defined as
      a plasma-free hemoglobin >40 mg/dl in association with clinical signs of
      hemolysis occurring at least 72 hours after LVAD implant. Descriptive statistics,
      time-dependent analyses and multivariable modeling were employed for statistical
      purposes. RESULTS: A total of 4,850 patients followed for a mean of 11.1 months
      comprised the final study population. There were 340 hemolytic events in 260
      patients. Freedom from hemolysis was 97% at 3 months, 94% at 1 year and 91% at 2
      years. Mean time from implant to first hemolysis event was 7.4 months. Younger
      age (<60 years) was independently associated with greater hemolysis (p < 0.001).
      Thrombotic device malfunction, device exchange and mortality were all
      significantly higher after hemolysis, with the greatest risk for each occurring
      within 6 months. CONCLUSIONS: Hemolysis is not a rare event after CF-LVAD
      implantation and is associated with an early increase in morbidity and death.
      Future study should focus on other device and implant characteristics that may
      lead to hemolytic events, as well as appropriate strategies for managing affected
      patients.

PMID- 25582037
TI  - Clinical and laboratory features of systemic sclerosis complicated with localized
      scleroderma.
AB  - Localized scleroderma (LSc) primarily affects skin, whereas systemic sclerosis
      (SSc) affects skin and various internal organs. LSc and SSc are considered to be
      basically different diseases, and there is no transition between them. However,
      LSc and SSc have several common characteristics, including endothelial cell
      dysfunction, immune activation, and excess fibrosis of the skin, and there exist
      several SSc cases complicated with LSc during the course of SSc. Clinical and
      laboratory characteristics of SSc patients with LSc remain unclear. We
      investigated the clinical and laboratory features of 8 SSc patients with LSc
      among 220 SSc patients (3.6%). The types of LSc included plaque (5/8), guttate
      (2/8), and linear type (1/8). All cases were diagnosed as having SSc within 5
      years before or after the appearance of LSc. In three cases of SSc with LSc
      (37.5%), LSc skin lesions preceded clinical symptoms of SSc. Young age, negative
      antinuclear antibody, and positive anti-RNA polymerase III antibody were
      significantly prevalent in SSc patients with LSc. The positivity of
      anticentromere antibody tended to be prevalent in SSc patients without LSc. No
      significant difference in the frequency of complications, such as interstitial
      lung disease, reflux esophagitis, and pulmonary artery hypertension, was
      observed. The awareness of these characteristic of SSc with LSc are essential to
      establish an early diagnosis and treatment.

PMID- 25582041
TI  - An overview of the endodontic curriculum in Fiji from 2009 to 2013.
AB  - This paper seeks to provide the reader with an overview of the endodontic
      curriculum in Fiji from 2009 to 2013. It also intends to inform readers of the
      changes in endodontic teaching, the learning methods utilised, curriculum
      development, the transition from block teaching to partial block teaching
      combined with longitudinal teaching, and the future plans for the endodontic
      module. 

PMID- 25582040
TI  - Staff attitudes towards people with intellectual disabilities in Japan and the
      United States.
AB  - BACKGROUND: Staff attitudes may affect choices available to persons with
      intellectual disabilities (ID). This study examined attitudes towards people with
      ID among staff working with people with ID in Japan and the United States.
      METHOD: Attitudes of staff working with people with ID in Japan and the United
      States were compared using the Community Living Attitudes Scale, Intellectual
      Disabilities Form. Responses were examined via multivariate analysis of variance.
      RESULTS: In unadjusted analyses, Japanese staff exhibited a greater tendency
      towards Sheltering and Exclusion of people with ID and lower endorsement of
      Empowerment and Similarity of people with ID. After controlling for covariates,
      the country effect was no longer significant for Sheltering and Exclusion. Age
      and education were significantly associated with attitudes in the adjusted model.
      CONCLUSIONS: While attitudes in Japan appeared less supportive of community
      inclusion of people with ID, some of the differences between countries were
      attributable to other staff characteristics such as age and education. Findings
      provide new information about how attitudes of staff in each country compare with
      each other.

PMID- 25582038
TI  - Exploiting host immunity: the Salmonella paradigm.
AB  - Pathogens have evolved clever strategies to evade and in some cases exploit the
      attacks of an activated immune system. Salmonella enterica is one such pathogen,
      exploiting multiple aspects of host defense to promote its replication in the
      host. Here we review recent findings on the mechanisms by which Salmonella
      establishes systemic and chronic infection, including strategies involving
      manipulation of innate immune signaling and inflammatory forms of cell death, as
      well as immune evasion by establishing residency in M2 macrophages. We also
      examine recent evidence showing that the oxidative environment and the high
      levels of antimicrobial proteins produced in response to localized Salmonella
      gastrointestinal infection enable the pathogen to successfully outcompete the
      resident gut microbiota. 

PMID- 25582042
TI  - Should emergency medicine registrars focus on seeing patients and leave the
      teaching of medical students to others? No.

PMID- 25582039
TI  - Confusing signals: recent progress in CTLA-4 biology.
AB  - The mechanism of action of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
      remains surprisingly unclear. Regulatory T (Treg) cells can use CTLA-4 to elicit
      suppression; however, CTLA-4 also operates in conventional T cells, reputedly by
      triggering inhibitory signals. Recently, interactions mediated via the CTLA-4
      cytoplasmic domain have been shown to preferentially affect Treg cells, yet other
      evidence suggests that the extracellular domain of CTLA-4 is sufficient to elicit
      suppression. Here, we discuss these paradoxical findings in the context of CTLA-4
      mediated ligand regulation. We propose that the function of CTLA-4 cytoplasmic
      domain is not to transmit inhibitory signals but to precisely control the
      turnover, cellular location, and membrane delivery of CTLA-4 to facilitate its
      central function: regulating the access of CD28 to their shared ligands. 

PMID- 25582045
TI  - Are we too many? A short essay on ophthamology demographics in Spain.

PMID- 25582043
TI  - The prevalence of primary headache disorders and their associated factors among
      nursing staff in North China.
AB  - BACKGROUND: Epidemiological data on the prevalence of headache in nursing staff
      in Mainland China are lacking. We therefore performed a study to assess the
      prevalence of headache, and factors associated with headaches, in nursing staff
      in three hospitals in North China. METHODS: Stratified random cluster sampling
      was used to select 1102 nurses from various departments in three hospitals. A
      structured questionnaire was used to collect epidemiological data, headache
      characteristics and associated factors. RESULTS: The response rate was 93.0%.
      Among nursing staff, the 1-year prevalence of primary headache disorders was
      45.3%, of migraine 14.8% (migraine with aura 3.4%, migraine without aura 11.4%),
      of tension-type headache (TTH) 26.2%, of chronic daily headache (CDH) 2.7%.
      Multivariate analysis showed that seniority (>=5 years) was a risk factor for
      migraine (OR 2.280), obesity (BMI >= 25) was a risk factor for TTH and CDH (OR
      1.684 and 3.184), and age (>=40 years) was a risk factor for CDH (OR 8.455).
      Nurses working in internal medicine were more likely to suffer CDH than those in
      other departments. Working a greater number of night shifts was also associated
      with increased prevalence of headache. CONCLUSION: The prevalence of primary
      headache disorders in nurses is higher than that in the general population in
      China, and occupational factors may play an important role. Therefore, the
      prevalence of headache in nurses should be a focus of attention, and coping
      strategies should be provided. Such measures could contribute to improving
      patient care.

PMID- 25582044
TI  - Increased body mass index predicts severity of asthma symptoms but not objective
      asthma traits in a large sample of asthmatics.
AB  - AIM: To examine the relationship between body mass index (BMI) and different
      indicators of asthma severity in a large community-based sample of Danish
      adolescents and adults. METHODS: A total of 1186 subjects, 14-44 years of age,
      who in a screening questionnaire had reported a history of airway symptoms
      suggestive of asthma and/or allergy, or who were taking any medication for these
      conditions were clinically examined. All participants were interviewed about
      respiratory symptoms and furthermore height and weight, skin test reactivity,
      lung function, and airway responsiveness were measured. RESULTS: A total of 516
      individuals had asthma. The mean BMI was 24.9 kg/m(2) (SD = 5.1). Asthma severity
      measured by GINA score increased with increasing BMI (p = 0.009). The result
      remained significant after adjusting for age, sex, medication use for asthma and
      smoking (p = 0.010). Severity of individual asthma symptoms; cough (p = 0.002)
      and chest tightness (p = 0.023) was also significantly related to BMI, whereas
      severity of wheezing and shortness of breath was not. Airway obstruction was more
      pronounced in subjects with increased BMI (p < 0.001) but the effect disappeared
      after adjustment for covariates (p = 0.233). Lung function, airway
      responsiveness, and atopy were not significantly related to BMI as were use of
      medication for asthma and adherence to treatment. CONCLUSIONS: In adults,
      increased body mass index predicts severity of asthma symptoms but not objective
      asthma traits.

PMID- 25582046
TI  - [Orbital anatomical changes in Retrato de familia. Adriaen Thomasz Key. El Prado
      National Museum, Madrid].

PMID- 25582047
TI  - [Neuro-ophthalmology in Oliver Sacks books: Visual auras].

PMID- 25582048
TI  - [Saint Lucy in El Prado Museum (VI). Retablo de la Virgen by the maestro of
      Torralba. Varez Fisa donation].

PMID- 25582049
TI  - [Is the standard operating times system applicable to ophthalmology in the public
      health system?].

PMID- 25582050
TI  - Video-assisted thoracoscopic surgery versus open thoracotomy for pulmonary
      metastasectomy: a systematic review.
AB  - BACKGROUND: Pulmonary metastasectomy has become a popular procedure for patients
      with pulmonary metastases. It can be achieved via the traditional open
      thoracotomy or the more recently developed video-assisted thoracoscopic surgery
      (VATS). However, there has been much debate as to which approach is better in
      terms of detection of pulmonary metastases and, in turn, survival and recurrence
      outcomes. We aim to compare the two different approaches in terms of survival and
      recurrence outcomes. METHODS: Medline and EMBASE databases were searched for
      relevant publications dated prior to May 2013. The bibliographies of the included
      articles were examined for additional relevant articles that were not included in
      the search. All publications reporting on overall survival and recurrence-free
      survival were included. The articles were carefully examined and data were
      extracted. STATA 12L and RevMan5.2 software were used to combine the data using
      the random effects model. RESULTS: A total of 1960 studies were identified
      through the search. Thirty-two articles had extractable data regarding overall
      survival and recurrence-free survival. However, only eight articles were included
      in the end as the other 24 articles had incomplete data. From the included
      articles, we found that the VATS group had slightly higher odds of 1-, 3- and 5
      year overall survival with odds ratios of 1.53, 1.69 and 1.41, respectively, and
      also higher odds of 1-, 3- and 5-year recurrence-free survival with odds ratios
      of 1.29, 1.54 and 1.54, respectively. CONCLUSION: VATS offers a suitable
      alternative to open thoracotomy for the treatment of pulmonary metastases.

PMID- 25582051
TI  - The use of novel phenotyping methods for validation of equine conformation
      scoring results.
AB  - In this experiment, which is based on a cohort of 44 Lipizzan mares from the
      Austrian state stud farm of Piber, we present new statistical techniques for the
      analysis of shape and equine conformation using image data. In addition, we
      examined which strategies and procedures of image processing techniques led to a
      successful interpretation of the traits implemented in horse breeding programs. A
      total of 246 two-dimensional anatomical and somatometric landmarks were digitized
      from standardized photographs, and the variation of shape has been analyzed by
      the use of generalized orthogonal least-squares Procrustes (generalized
      Procrustes analysis (GPA)) procedures. The resulting shape variables have been
      regressed on the results from linear type trait classifications. In addition, the
      rating scores of six conformation classifiers were tested for agreement, yielding
      an inter-rater correlation (inter-class correlation) ranging from 0.41 to 0.68,
      respectively, a kappa coefficient ranging from 0.16 to 0.53. From the 12 linear
      type traits assessed on a valuating scale, only the type-related traits (type,
      breed-type and harmony) revealed significant (P<0.05) results in the regression
      analysis of shape variables on linear type traits. The other nine traits were
      characterized by a lower agreement between classifiers and did not result in a
      significant 'shape regression'. Finally, the 'horse shape space' defined by shape
      variables resulting from GPA procedures offered the possibility to assist in
      trait definition and in the evaluation of ratings, and it is an adequate
      biological and objective scale to human perception of conformation, which is
      expressed in numerical data only. 

PMID- 25582052
TI  - Reconstruction of atonic bladder innervation after spinal cord injury: A bladder
      reflex arc with afferent and efferent pathways.
AB  - Background Establishing bladder reflex arcs only with the efferent pathway to
      induce micturition after spinal cord injury (SCI) has been successful. However,
      the absence of sensory function and micturition desires can lead to serious
      complications. Objectives To reconstruct a bladder reflex arc with both afferent
      and efferent pathways to achieve atonic bladder innervation after SCI. Methods A
      reflex arc was established by microanastomosis of the S2 dorsal root to the
      peripheral process of the L5 dorsal ganglion and the L5 ventral root to the S2
      ventral root. The functions of the reflex arc were evaluated using
      electrophysiology, wheat germ agglutinin-horseradish peroxidase (WGA-HRP)
      tracing, and calcitonin gene-related peptide (CGRP) immunocytochemistry analysis.
      Hind-paw motion was evaluated by CatWalk gait. Results Compound action potentials
      and compound muscle action potentials were recorded at the right L5 dorsal root
      following electrical stimulation of right S2 dorsal root. Similar to the control
      side, these were not significantly different before or after the spinal cord
      destruction between L6 and S4. WGA-HRP tracing and CGRP immunocytochemistry
      showed that construction of the afferent and efferent pathways of the bladder
      reflex arc encouraged axonal regeneration of motor and sensory nerves, which then
      made contact with the anterior and posterior horns of the spinal cord, ultimately
      reestablishing axoplasmic transportation. Gait analysis showed that at 3 months
      following the operation, only the regularity index was significantly different as
      compared with 1 day before the operation, other parameters showing no difference.
      Conclusion Bladder reflex arc with the afferent and efferent pathways
      reconstructs the micturition function without great influence on the motion of
      leg. 

PMID- 25582053
TI  - Complement C5a receptor gene 450 C/T polymorphism in renal transplant recipients:
      association of the CT genotype with graft outcome.
AB  - Complement-mediated humoral rejection has become the main focus of research in
      organ transplantation. The aim of this study was to investigate the possible
      association of the complement C5aR gene 450 C/T polymorphism in antibody-mediated
      renal allograft rejection. This polymorphism was investigated in 290 first
      deceased donor kidney graft recipients with well functioning grafts and no
      rejection treatment during the first transplant year (WFG), 265 recipients with
      graft failure within the first transplant year (F), and 187 healthy controls.
      Frequency of the 450 CT genotype was lower in the total population of 555 kidney
      recipients (4.7%) than in 187 healthy controls (8.6%), but the difference was not
      statistically significant (P = 0.065). A significantly higher frequency of CT
      genotype was found in F patients (CT: 6.8%) when compared to WFG patients (CT:
      2.8%, P = 0.027). The CT genotype was also significantly lower in WFG patients
      than in healthy controls (P = 0.009). Low frequency of the C5aR 450 CT genotype,
      which apparently is a feature of certain kidney diseases, appears to be
      associated with good graft outcome in kidney transplantation and might be helpful
      for identifying recipients who are at low risk for graft rejection. 

PMID- 25582054
TI  - The left sided predominance of breast cancer is decreasing.

PMID- 25582056
TI  - Predictive genetic testing in minors for Myocilin juvenile onset open angle
      glaucoma.
AB  - Myocilin glaucoma is an autosomal dominant disorder leading to irreversible
      blindness, but early intervention can minimize vision loss and delay disease
      progression. The purpose of this study was to discuss the benefits of predictive
      genetic testing in minors for Myocilin mutations associated with childhood onset
      glaucoma. Three families with Myocilin mutations associated with an age of onset
      before 18 years and six unaffected at-risk children were identified. Predictive
      genetic testing was discussed with the parents and offered for at-risk minors.
      Parents opted for genetic testing in half of the cases. None carried the familial
      mutation. The age of disease onset in the family, the severity of the condition,
      and the age of the child are all factors that appear to influence the decision of
      the parent to test their children. Predictive genetic testing for early onset
      Myocilin glaucoma can facilitate early detection of disease or discharge from
      routine ophthalmic examinations. 

PMID- 25582055
TI  - Modulation of microRNA editing, expression and processing by ADAR2 deaminase in
      glioblastoma.
AB  - BACKGROUND: ADAR enzymes convert adenosines to inosines within double-stranded
      RNAs, including microRNA (miRNA) precursors, with important consequences on miRNA
      retargeting and expression. ADAR2 activity is impaired in glioblastoma and its
      rescue has anti-tumoral effects. However, how ADAR2 activity may impact the
      miRNome and the progression of glioblastoma is not known. RESULTS: By integrating
      deep-sequencing and array approaches with bioinformatics analyses and molecular
      studies, we show that ADAR2 is essential to edit a small number of mature miRNAs
      and to significantly modulate the expression of about 90 miRNAs in glioblastoma
      cells. Specifically, the rescue of ADAR2 activity in cancer cells recovers the
      edited miRNA population lost in glioblastoma cell lines and tissues, and
      rebalances expression of onco-miRNAs and tumor suppressor miRNAs to the levels
      observed in normal human brain. We report that the major effect of ADAR2 is to
      reduce the expression of a large number of miRNAs, most of which act as onco
      miRNAs. ADAR2 can edit miR-222/221 and miR-21 precursors and decrease the
      expression of the corresponding mature onco-miRNAs in vivo and in vitro, with
      important effects on cell proliferation and migration. CONCLUSIONS: Our findings
      disclose an additional layer of complexity in miRNome regulation and provide
      information to better understand the impact of ADAR2 editing enzyme in
      glioblastoma. We propose that ADAR2 is a key factor for maintaining edited-miRNA
      population and balancing the expression of several essential miRNAs involved in
      cancer.

PMID- 25582057
TI  - Development of a nanoparticle-assisted PCR (nanoPCR) assay for detection of mink
      enteritis virus (MEV) and genetic characterization of the NS1 gene in four
      Chinese MEV strains.
AB  - BACKGROUND: Mink enteritis virus (MEV) causes mink viral enteritis, an acute and
      highly contagious disease whose symptoms include violent diarrhea, and which is
      characterized by high morbidity and mortality. Nanoparticle-assisted polymerase
      chain reaction (nanoPCR) is a recently developed technique for the rapid
      detection of bacterial and viral DNA. Here we describe a novel nanoPCR assay for
      the clinical detection and epidemiological characterization of MEV. RESULTS: This
      assay is based upon primers specific for the conserved region of the MEV NS1
      gene, which encodes nonstructural protein 1. Under optimized conditions, the MEV
      nanoPCR assay had a detection limit of 8.75 * 10(1) copies recombinant plasmids
      per reaction, compared with 8.75 * 10(3) copies for conventional PCR analysis.
      Moreover, of 246 clinical mink samples collected from five provinces in North
      Eastern China, 50.8% were scored MEV positive by our nanoPCR assay, compared with
      32.5% for conventional PCR. Furthermore no cross reactivity was observed for the
      nanoPCR assay with respect to related viruses, including canine distemper virus
      (CDV) and Aleutian mink disease parvovirus (AMDV). Phylogenetic analysis of four
      Chinese wild type MEV isolates using the nanoPCR assay indicated that they
      belonged to a small MEV clade, named "China type", in the MEV/FPLV cluster, and
      were closely clustered in the same location. CONCLUSIONS: Our results indicate
      that the MEV China type clade is currently circulating in domestic minks in
      China. We anticipate that the nanoPCR assay we have described here will be useful
      for the detection and epidemiological and pathological characterization of MEV.

PMID- 25582058
TI  - Alumina reinforced zirconia implants: effects of cyclic loading and abutment
      modification on fracture resistance.
AB  - OBJECTIVE: The aim of the study was to evaluate the thermomechanical behavior of
      alumina-toughened zirconia (ATZ) oral implants in the artificial mouth and the
      fracture resistance (fracture load and bending moment) in a subsequent static
      fracture load test. The effects of abutment modification and different cyclic
      loadings were evaluated. METHODS: A total of 48 implants were used. 24 implants
      were left as machined (Group A), and 24 implants were shape modified at the
      abutment (Group B). Groups were divided into three subgroups composed of 8
      samples each (A1/B1: no cyclic loading; A2/B2: 1.2 million cycles; A3/B3: 5
      million cycles). Subsequently, all implants were statically loaded to the point
      of fracture. RESULTS: The implants showed the following survival rates after the
      artificial mouth: A2 and B2 100%; A3 and B3 87.5%. The following average fracture
      resistance values were found (fracture load [N]/bending moment [Nmm]): A1
      (583/2907), B1 (516/2825), A2 (618/2737), B2 (550/3150), A3 (802/3784) and B3
      (722/3809). After 5 million loading cycles a significant increase in fracture
      load and bending moment was found. Modification of the abutment significantly
      decreased the fracture load of implants without foregoing dynamic loading.
      However, the shape modification altered the lever arm. For that reason, a smaller
      load resulted in the same bending moment. Therefore, abutment modification had no
      significant influence on the fracture resistance of ATZ. SIGNIFICANCE: Neither
      thermomechanical cycling in an aqueous environment nor modification of the
      abutment had a negative effect on the fracture resistance of ATZ.

PMID- 25582059
TI  - Surface biocompatibility of differently textured titanium implants with
      mesenchymal stem cells.
AB  - OBJECTIVE: The major challenge for contemporary dentistry is restoration of
      missing teeth; currently, dental implantation is the treatment of choice in this
      circumstance. In the present study, we assessed the interaction between implants
      and Dental Pulp Stem Cells (DPSCs) in vitro by means of 3D cell culture in order
      to better simulate physiological conditions. METHODS: Sorted CD34+ DPSCs were
      seeded onto dental implants having either a rough surface (TriVent) or one coated
      with a ceramic layer mimicking native bone (TiUnite). We evaluated preservation
      of DPSC viability during osteogenic differentiation by an MTT assay and compared
      mineralized matrix deposition with SEM analysis and histological staining;
      temporal expression of osteogenic markers was evaluated by RT-PCR and ELISA.
      RESULTS: Both surfaces are equally biocompatible, preserve DPSC viability,
      stimulate osteogenic differentiation, and increase the production of VEGF. A
      slight difference was observed between the two surfaces concerning the speed of
      DPSC differentiation. SIGNIFICANCE: Our study of the two implant surfaces
      suggests that TriVent, with its roughness, is capable of promoting cell
      differentiation a bit earlier than the TiUnite surface, although the latter
      promotes greater cell proliferation.

PMID- 25582060
TI  - Antimicrobial properties of conventional restorative filling materials and
      advances in antimicrobial properties of composite resins and glass ionomer
      cements-A literature review.
AB  - OBJECTIVES: It has been reported that complete caries removal from cavities
      during restoration of teeth is difficult. Furthermore with the tissue saving
      approach it is expected that more of the saved affected tissue will possibly
      harbor more residual bacteria. Antimicrobial restorative filling materials would
      be ideal to prevent the spread of caries after completion of tooth restoration,
      thus preventing recurrent decay and eventually restoration failure. This paper
      reviews the literature on the antimicrobial properties of dental restorative
      filling materials. METHODS: Pubmed searches on the antibacterial properties of
      restorative materials were carried out. Keywords were chosen to assess
      antibacterial properties of conventional filling materials. Methods of
      introducing antimicrobial agents in restorative materials were also reviewed
      together with the methodology used to assess antimicrobial activity. RESULTS: 174
      articles from 1983 till 2014 were included. SIGNIFICANCE: Adhesive materials have
      decreased antimicrobial activity when compared to amalgams and zinc oxides.
      Several techniques have been employed in order to increase the antimicrobial
      activity of restorative materials. Although antimicrobial activity of restorative
      materials is important, the introduction of antimicrobial agents/techniques
      should not be at the expense of other material properties. Environmental changes
      within a material may affect the bacterial response to the antimicrobial.
      Bacterial adhesion to the restorative materials should be assessed. Long term
      assessment of antimicrobial activity is important and is clinically relevant. The
      use of antimicrobial dental materials is important unless such characteristics
      are gained to the detriment of other material properties.

PMID- 25582061
TI  - Bulk-fill resin composites: polymerization properties and extended light curing.
AB  - OBJECTIVES: The aim was to evaluate the polymerization properties of bulk-fill
      resin composites using two different light-curing protocols, in terms of degree
      of conversion (%DC), Vickers hardness (HV), polymerization volume shrinkage (PVS)
      and polymerization shrinkage stress (PSS) and compare them to conventional
      condensable and flowable resin composites. MATERIALS AND METHODS: Filtek BulkFill
      (FBF, 3MESPE, Germany), SDR (Dentsply, Germany), TetricEvoCeram BulkFill (TBF,
      Ivoclar-Vivadent, Liechtenstein), Venus BulkFill (VBF, Heraeus, Germany), X
      traBase (XTB, Voco, Germany), FiltekZ250 (3MESPE) and Filtek Supreme XTE Flowable
      (FSF, 3MESPE) were investigated. Light-curing was performed for 30 s or according
      to manufacturers' instructions (1200 mW/cm2, Bluephase20i, Ivoclar-Vivadent). For
      %DC and HV, discs (n=5) of 2 or 4 mm in thickness were prepared and stored for
      24h in distilled water at 37 degrees C. %DC was determined by FTIR-ATR
      spectroscopy. %DC and HV were measured at the top and bottom of the specimens.
      PVS was measured using Archimedes method (n=6). PSS measurements (n=10) were
      carried out using 5 mm diameter PMMA rods as bonding substrates with a specimen
      height of 1 mm in a universal testing machine. Data were analyzed using one- and
      two-way ANOVA (alpha=0.05). RESULTS: Except Z250 in the manufacturers' light
      curing mode, all materials showed no significant inferior %DC at 4 mm thickness.
      When light cured for 30 s Z250 had no significant differences in %DC at 2 or 4 mm
      when compared to top. FBF, TBF, FSF and Z250 displayed significant reduced HV at
      4 mm in both curing modes. Z250 and TBF showed the lowest PVS and FSF the highest
      PSS in both curing modes. SIGNIFICANCE: All investigated bulk-fill composites
      obtained sufficient polymerization properties at 4 mm depth. Enhanced curing time
      improved the investigated polymerization properties of bulk-fills and Z250.

PMID- 25582062
TI  - Development of locomotion in a subsocial spider.
AB  - Following consumption of their mother, the subsocial spider Amaurobius ferox
      remain together, exhibiting distinctive behaviours in response to intruders into
      the natal nest. We examined the ontogeny and characteristics of locomotory
      behaviours in A. ferox during this post-maternal social period. Locomotion of the
      spiderlings, elicited by the introduction of a cricket larva into the natal web,
      fell into two categories: 'abrupt locomotion' (AL) and 'ordinary locomotion'
      (OL). AL involved rapid and linear movement, whereas OL involved slower motion,
      not necessarily in a straight line. Both types of locomotion varied with
      spiderling age. AL appeared for only a limited period of time whereas the
      frequency of OL increased linearly over time. AL occurred more collectively than
      OL: the percentage of participants in a bout of locomotion was 18.67+/-17.71% vs.
      10.22+/-9.33%. The collective tendency of AL increased up until the seventh day
      and then decreased, whereas that of OL progressively decreased. The direction of
      AL responses to the intruder did not vary over time; however, for OL, movements
      towards increased in frequency over time. Locomotory responses also varied with
      the intensity of intruder movement. Including transient behaviours, the
      chronology of different behaviours suggests that behavioural development in A.
      ferox involves maternal influences and weakens group cohesion and collective
      tendency. 

PMID- 25582063
TI  - [Impact on the improvement of paediatric emergency services using a standardised
      model for the declaration and analysis of incidents].
AB  - INTRODUCTION: The aim of this study is to analyse changes in the incidents
      reported after the implementation of a new model, and study its results on
      patient safety. PATIENTS AND METHODS: In 2012 an observational study with
      prospective collection of incidents reported between 2007 and 2011 was conducted.
      In May 2012 a model change was made in order to increase the number of reports,
      analyse their causes, and improve the feedback to the service. Professional
      safety representatives were assigned to every department, information and
      diffusion sessions were held, and a new incident reporting system was
      implemented. With the new model, a new observational study with prospective
      collection of the reports during one year was initiated, and the results compared
      between models. RESULTS: In 2011, only 19 incidents were reported in the
      Emergency Department, and between June 1, 2012 to June 1, 2013, 106 incidents
      (5.6 times more). The incidents reported were medication incidents (57%),
      identification (26%), and procedures (7%). The most frequent causes were human
      (70.7%), lack of training (22.6%), and working conditions (15.1%). Some measures
      were implemented as a result of these incidents: a surgical checklist, unit doses
      of salbutamol, tables of weight-standardised doses of drugs for cardiopulmonary
      resuscitation. CONCLUSIONS: The new model of reporting incidents has enhanced the
      reports and has allowed improvements and the implementation of preventive
      measures, increasing the patient safety in the Emergency Department.

PMID- 25582064
TI  - Editorial: Increased manuscript submissions prompt journals to make hard choices.

PMID- 25582065
TI  - CORR Insights((r)): The Gown-glove Interface Is a Source of Contamination: A
      Comparative Study.

PMID- 25582066
TI  - What is the Proportion of Patients With Multiple Hereditary Exostoses Who Undergo
      Malignant Degeneration?
AB  - BACKGROUND: Multiple hereditary exostoses is an autosomal-dominant skeletal
      disorder that has a wide-ranging reported risk of malignant degeneration to
      chondrosarcoma. QUESTIONS/PURPOSES: The aims of our study were to use a large,
      web-based survey approach to characterize (1) the demographic distribution of
      patients with multiple hereditary exostoses, (2) the number of surgeries
      performed related to one's diagnosis of multiple hereditary exostoses, and (3)
      the proportion of survey respondents who described experiencing malignant
      degeneration in a large international, heterogeneous cohort of patients with
      multiple hereditary exostoses. METHODS: An anonymous web-based survey was
      distributed to several online support groups and social media networks designed
      to support and educate patients with multiple hereditary exostoses and their
      families. The survey collected demographic and epidemiologic data on 779
      respondents. Data were recorded to assess respondents' disease burden and the
      rate of malignant degeneration. RESULTS: Females represented a slightly greater
      proportion of those with multiple hereditary exostoses who responded (56% female;
      419 of 742 patients). Median age for all respondents was 28 years (range, < 1-85
      years). Median age for males was 25 years (range, < 1-85 years), while median age
      for females was 29 years (range, < 1-82 years). The mean age at diagnosis of male
      and female respondents was in the mid-first decade (5.4 years +/- 7.2 years). The
      mean number of surgeries a patient had undergone was 7.3 (+/- 7.1 surgeries). The
      proportion of respondents who experienced malignant transformation was 2.7% (21
      of 757 respondents), at a mean age of 28.6 years (+/- 9.3 years). The most common
      sites of malignant change from benign exostoses included the pelvis (eight of 21
      respondents) and scapula (four of 21 respondents). CONCLUSIONS: In the largest
      and most geographically diverse study of patients with multiple hereditary
      exostoses of which we are aware, we found the proportion of patients with
      multiple hereditary exostoses who have undergone malignant degeneration to be
      consistent with those reported in prior studies. Our study perhaps more
      accurately assessed the proportion of patients who undergo malignant
      transformation of multiple hereditary exostoses. As with prior studies on this
      topic, the proportion of malignant change may be expected to represent a high-end
      estimate as recruitment and selection bias likely predisposes for patients with
      more severe disease, whereas patients with lesser disease may be unaware of their
      diagnosis. In discussing the sequelae of multiple hereditary exostoses,
      clinicians perhaps might use this study to offer an unspecific statement of risk
      of malignant degeneration of multiple hereditary exostoses among the population
      at large. LEVEL OF EVIDENCE: Level IV, prognostic study.

PMID- 25582068
TI  - Speciation within Columnea section Angustiflora (Gesneriaceae): islands,
      pollinators and climate.
AB  - Despite many advances in evolutionary biology, understanding the proximate
      mechanisms that lead to speciation for many taxonomic groups remains elusive.
      Phylogenetic analyses provide a means to generate well-supported estimates of
      species relationships. Understanding how genetic isolation (restricted gene flow)
      occurred in the past requires not only a well-supported molecular phylogenetic
      analysis, but also an understanding of when character states that define species
      may have changed. In this study, phylogenetic trees resolve species level
      relationships for fourteen of the fifteen species within Columnea section
      Angustiflorae (Gesneriaceae). The distributions of sister species pairs are
      compared and ancestral character states are reconstructed using Bayesian
      stochastic mapping. Climate variables were also assessed and shifts in ancestral
      climate conditions were mapped using SEEVA. The relationships between
      morphological character states and climate variables were assessed with
      correlation analyses. These results indicate that species in section
      Angustiflorae have likely diverged as a result of allopatric, parapatric, and
      sympatric speciation, with both biotic and abiotic forces driving morphological
      and phenological divergence. 

PMID- 25582069
TI  - The BCL2 antagonist ABT-199 triggers apoptosis, and augments ibrutinib and
      idelalisib mediated cytotoxicity in CXCR4 Wild-type and CXCR4 WHIM mutated
      Waldenstrom macroglobulinaemia cells.

PMID- 25582070
TI  - Four-year to seven-year outcomes of advanced surface ablation with excimer laser
      for high myopia.
AB  - PURPOSE: We aimed to evaluate and compare outcomes after photorefractive
      keratectomy with cooling (cPRK) and laser-assisted subepithelial keratectomy
      (LASEK) for high myopia. METHODS: This was a retrospective, single-masked follow
      up study of patients treated for myopia between 2007 and 2009 with cPRK or LASEK,
      using a high-frequency flying-spot excimer laser with eye-tracker (MEL80; Carl
      Zeiss, Jena, Germany). One eye of each patient was randomly chosen for analysis.
      Re-treated eyes were excluded. RESULTS: Forty-six cPRK patients and 35 LASEK
      patients were included. Spherical equivalent averaged -7.69 +/- 1.47 diopters (D)
      in cPRK eyes and -7.98 +/- 2.06 D in LASEK eyes (p = 0.31) before surgery. The
      average follow-up time was 4.6 years in cPRK patients and 6.0 years in LASEK
      patients (p < 0.05). At final follow-up, no cPRK eyes and one LASEK eye (p =
      0.46) had lost two lines of corrected distance visual acuity (CDVA). No eyes had
      significant haze at final follow-up, although trace haze was found in four cPRK
      eyes and six LASEK eyes (p = 0.44). However, at 6 weeks after surgery, zero cPRK
      eyes and nine LASEK eyes (p < 0.05) had significant haze. At final follow-up, 63
      % of cPRK eyes and 35 % of LASEK eyes (p = 0.17) were within +/-1.0 D of intended
      refraction. Finally, 100 % of cPRK patients and 92 % of LASEK patients (p = 0.87)
      were satisfied or very satisfied with the surgery at final follow-up. CONCLUSION:
      cPRK and LASEK seemed safe and with high patient satisfaction 4 to 7 years after
      surgery for high myopia. However, cPRK was more effective than LASEK in reducing
      initial significant corneal haze.

PMID- 25582071
TI  - ValWorkBench: an open source Java library for cluster validation, with
      applications to microarray data analysis.
AB  - The prediction of the number of clusters in a dataset, in particular microarrays,
      is a fundamental task in biological data analysis, usually performed via
      validation measures. Unfortunately, it has received very little attention and in
      fact there is a growing need for software tools/libraries dedicated to it. Here
      we present ValWorkBench, a software library consisting of eleven well known
      validation measures, together with novel heuristic approximations for some of
      them. The main objective of this paper is to provide the interested researcher
      with the full software documentation of an open source cluster validation
      platform having the main features of being easily extendible in a homogeneous way
      and of offering software components that can be readily re-used. Consequently,
      the focus of the presentation is on the architecture of the library, since it
      provides an essential map that can be used to access the full software
      documentation, which is available at the supplementary material website [1]. The
      mentioned main features of ValWorkBench are also discussed and exemplified, with
      emphasis on software abstraction design and re-usability. A comparison with
      existing cluster validation software libraries, mainly in terms of the mentioned
      features, is also offered. It suggests that ValWorkBench is a much needed
      contribution to the microarray software development/algorithm engineering
      community. For completeness, it is important to mention that previous accurate
      algorithmic experimental analysis of the relative merits of each of the
      implemented measures [19,23,25], carried out specifically on microarray data,
      gives useful insights on the effectiveness of ValWorkBench for cluster validation
      to researchers in the microarray community interested in its use for the
      mentioned task. 

PMID- 25582072
TI  - Reasons for discontinuation of recommended therapies according to the patients
      after acute coronary syndromes.
AB  - BACKGROUND: The prescription of recommended medical therapies is a key factor to
      improve prognosis after acute coronary syndromes (ACS). However, reasons for
      cardiovascular therapies discontinuation after hospital discharge are poorly
      reported in previous studies. METHODS: We enrolled 3055 consecutive patients
      hospitalized with a main diagnosis of ACS in four Swiss university hospitals with
      a prospective one-year follow-up. We assessed the self-reported use of
      recommended therapies and the reasons for medication discontinuation according to
      the patient interview performed at one-year follow-up. RESULTS: 3014 (99.3%)
      patients were discharged with aspirin, 2983 (98.4%) with statin, 2464 (81.2%)
      with beta-blocker, 2738 (90.3%) with ACE inhibitors/ARB and 2597 (100%) with
      P2Y12 inhibitors if treated with coronary stent. At the one-year follow-up, the
      discontinuation percentages were 2.9% for aspirin, 6.6% for statin, 11.6% for
      beta-blocker, 15.1% for ACE inhibitor/ARB and 17.8% for P2Y12 inhibitors. Most
      patients reported having discontinued their medication based on their physicians'
      decision: 64 (2.1%) for aspirin, 82 (2.7%) for statin, 212 (8.6%) for beta
      blocker, 251 (9.1% for ACE inhibitor/ARB) and 293 (11.4%) for P2Y12 inhibitors,
      while side effect, perception that medication was unnecessary and medication
      costs were uncommon reported reasons (<2%) according to the patients.
      CONCLUSIONS: Discontinuation of recommended therapies after ACS differs according
      the class of medication with the lowest percentages for aspirin. According to
      patients, most stopped their cardiovascular medication based on their physician's
      decision, while spontaneous discontinuation was infrequent.

PMID- 25582074
TI  - Impact on human health of climate changes.
AB  - There is increasing evidence that climate is rapidly changing. These changes,
      which are mainly driven by the dramatic increase of greenhouse gas emissions from
      anthropogenic activities, have the potential to affect human health in several
      ways. These include a global rise in average temperature, an increased frequency
      of heat waves, of weather events such as hurricanes, cyclones and drought
      periods, plus an altered distribution of allergens and vector-borne infectious
      diseases. The cardiopulmonary system and the gastrointestinal tract are
      particularly vulnerable to the adverse effects of global warming. Moreover, some
      infectious diseases and their animal vectors are influenced by climate changes,
      resulting in higher risk of typhus, cholera, malaria, dengue and West Nile virus
      infection. On the other hand, at mid latitudes warming may reduce the rate of
      diseases related to cold temperatures (such as pneumonia, bronchitis and
      arthritis), but these benefits are unlikely to rebalance the risks associated to
      warming. 

PMID- 25582073
TI  - Cardiovascular profile in critically ill elderly medical patients: prevalence,
      mortality and length of stay.
AB  - PURPOSE: Data are demonstrating the increase in utilization of critical care by
      the elderly. Around 11% of ICU patients are >=80years-old. METHODS: An
      observational retrospective study was conducted between 2003 and 2011, including
      elderly patients (>=80years old) admitted from medical services to the intensive
      care unit (ICU) in a tertiary university hospital. The final sample size was
      N=202. RESULTS: Mortality rates were: ICU 34.1%, in-hospital 44% and 1-year
      cumulative mortality 55.4% (20.4% for hospital survivors). Multivariate analysis
      showed that APACHE II score: OR 1.10, 95% CI (1.03-1.18), SAPS II score: OR 1.03,
      95% CI (1.01-1.06), a score <3 on the Cruz Roja Hospital mental scale: 0.51 OR,
      95% CI (0.01-0.57) and ICU admission for cardiovascular disease: OR 5.05, 95% CI
      (1.98-12.84) were independently associated with mortality ICU. Factors
      independently associated with 1-year mortality were: dyslipidemia OR 7.25 (1.47
      35.60), chronic kidney failure OR 13.23, 95% CI (2.28-76.6), stroke OR 10.44, 95%
      CI (2.26-48.25) and antihypertensive treatment OR 0.08, 95% CI (0.01-0.48). In
      multiple linear regression, ICU length of stay was associated with mechanical
      ventilation B coefficient 6.41, 95% CI (1.18-11.64) and in-hospital length of
      stay was related to age: B coefficient -2.17, 95% CI (-4.02 to -0.33).
      CONCLUSIONS: Prevalence of cardiovascular risk factors and cardiovascular disease
      was high, and basal cardiovascular treatment was underused. Primary diagnosis for
      cardiovascular disease at ICU admission should be assessed as predictor of ICU
      mortality. Intensifying cardiovascular basal treatment could decrease 1-year
      mortality. Cardiovascular profile did not show an effect on in-hospital mortality
      and length of stay.

PMID- 25582075
TI  - Emergency readmissions are substantially determined by acute illness severity and
      chronic debilitating illness: a single centre cohort study.
AB  - BACKGROUND: The factors influencing hospital readmissions are debated. We
      assessed whether readmissions could be predicted using routinely collected
      hospital data. METHODS: All emergency admissions to a single institution over
      12years (2002-2013) were included. The predictor variables, of acute illness
      severity, Manchester Triage Category, chronic disabling disease and Charlson co
      morbidity scores, were studied univariably and entered into a multivariable
      logistic regression model to predict the bivariate of any readmission or none. A
      zero truncated Poisson regression model assessed the predictors against the
      readmission count and incidence rate ratios were calculated. Factors reflecting
      the clinical load on the emergency department were examined. RESULTS: 66,933
      admissions were recorded in 36,271 patients. The readmission rates at 1, 3, 6 and
      9years were 29.5%, 38.9%, 42.9% and 44.1%. Early readmissions represented 14.1%.
      In the multivariable model, an admission in the previous 6months was the
      strongest predictor of readmission, OR of 5.02 (95% CI: 4.86, 5.18). Acute
      illness severity - OR of 2.68 (95% CI: 2.33, 3.09) for group VI vs group I, and
      chronic disabling score - OR of 2.08 (95% CI: 1.87, 2.32) for a score of 4+ vs 0
      were significant predictors of readmission in the multivariable model. Both of
      these predictors demonstrated a linear relationship. Illness severity was the
      strongest predictor of an early readmission within 4weeks. CONCLUSION:
      Readmissions increase as a function of time; illness severity, chronic disabling
      disease score and a recent admission are the strongest predictors of readmission.

PMID- 25582076
TI  - Poly I:C enhances production of nitric oxide in response to interferon-gamma via
      upregulation of interferon regulatory factor 7 in vascular endothelial cells.
AB  - The effect of poly I:C on interferon (IFN)-gamma-induced nitric oxide (NO)
      production in vascular endothelial cells was examined using murine aortic
      endothelial END-D cells. Poly I:C augmented IFN-gamma-induced NO production
      although it alone did not induce the NO production. Poly I:C augmented the NO
      production via enhanced expression of an inducible NO synthase protein. Poly I:C
      did not affect the activation of Janus kinase (JAK) 1/2, and signal transducer
      and activator of transcription (STAT) 1 in IFN-gamma signaling. Moreover, there
      was no significant difference in the IFN-gamma-induced interferon regulatory
      factor (IRF) 1 expression between the presence and absence of poly I:C. Poly I:C
      led to the activation of IRF7 in END-D cells. Inhibition of poly I:C signaling by
      amlexanox, an inhibitor of TANK-binding kinase (TBK) 1 and IkappaB kinase (IKK)
      epsilon, abolished the augmentation of IFN-gamma-induced NO production.
      Therefore, poly I:C was suggested to augment IFN-gamma-induced NO production at
      the transcriptional level via enhanced IRF7 activation. 

PMID- 25582077
TI  - Pleiotrophin-induced endothelial cell migration is regulated by xanthine oxidase
      mediated generation of reactive oxygen species.
AB  - Pleiotrophin (PTN) is a heparin-binding growth factor that induces cell migration
      through binding to its receptor protein tyrosine phosphatase beta/zeta
      (RPTPbeta/zeta) and integrin alpha v beta 3 (alphanubeta3). In the present work,
      we studied the effect of PTN on the generation of reactive oxygen species (ROS)
      in human endothelial cells and the involvement of ROS in PTN-induced cell
      migration. Exogenous PTN significantly increased ROS levels in a concentration
      and time-dependent manner in both human endothelial and prostate cancer cells,
      while knockdown of endogenous PTN expression in prostate cancer cells
      significantly down-regulated ROS production. Suppression of RPTPbeta/zeta through
      genetic and pharmacological approaches, or inhibition of c-src kinase activity
      abolished PTN-induced ROS generation. A synthetic peptide that blocks PTN
      alphanubeta3 interaction abolished PTN-induced ROS generation, suggesting that
      alphanubeta3 is also involved. The latter was confirmed in CHO cells that do not
      express beta3 or over-express wild-type beta3 or mutant beta3Y773F/Y785F. PTN
      increased ROS generation in cells expressing wild-type beta3 but not in cells not
      expressing or expressing mutant beta3. Phosphoinositide 3-kinase (PI3K) or Erk1/2
      inhibition suppressed PTN-induced ROS production, suggesting that ROS production
      lays down-stream of PI3K or Erk1/2 activation by PTN. Finally, ROS scavenging and
      xanthine oxidase inhibition completely abolished both PTN-induced ROS generation
      and cell migration, while NADPH oxidase inhibition had no effect. Collectively,
      these data suggest that xanthine oxidase-mediated ROS production is required for
      PTN-induced cell migration through the cell membrane functional complex of
      alphanubeta3 and RPTPbeta/zeta and activation of c-src, PI3K and ERK1/2 kinases. 

PMID- 25582078
TI  - Skin autofluorescence is associated with carotid intima-media thickness, diabetic
      microangiopathy, and long-lasting metabolic control in type 1 diabetic patients.
      Results from Poznan Prospective Study.
AB  - AIMS: Our aim was to assess the association between skin autofluorescence (AF)
      related to advanced glycation end products (AGEs) accumulation and long-term
      metabolic control, microvascular complications and carotid intima-media thickness
      (IMT) in an observational cohort of type 1 diabetes (DM1). METHODS: The analysis
      included 77 patients with DM1 (28 women and 49 men) aged 38 (IQR: 34-41),
      diabetes duration 15 (14-17), participating in Poznan Prospective Study
      (PoProStu). Skin AF was measured with AGE Reader (DiagnOptics). RESULTS: We found
      50% of any microvascular complication; 37% of retinopathy, 37% of diabetic kidney
      disease and 22% of distal symmetrical neuropathy. Median carotid IMT was 0.57
      (0.52-0.67) mm and skin AF 2.2 (IQR: 1.9-2.6). We found positive correlation
      between skin AF and patients' age (r=0.31, p=0.006), mean HbA1c from the
      observation time (r=0.35, p=0.001) and IMT (r=0.39, p<0.001). In multivariate
      logistic regression presence of microvascular complications was independently
      associated with skin AF: for retinopathy (OR 3.49; 95% CI: 1.08-11.28, p=0.03),
      for diabetic kidney disease (OR 3.62; 95% CI: 1.16-11.28, p=0.02), for neuropathy
      (OR 5.01; 95% CI: 1.21-20.77, p=0.02) and for any microangiopathy (OR 3.13; 95%
      CI: 1.06-9.18, p=0.03). CONCLUSION: Skin AF is a reliable marker of past glycemic
      control of diabetes. Increased accumulation of AGEs is related to the presence of
      diabetic microangiopathy as well as subclinical macroangiopathy in patients with
      type 1.

PMID- 25582079
TI  - MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes.
AB  - The piRNA machinery is known for its role in mediating epigenetic silencing of
      transposons. Recent studies suggest that this function also involves piRNA-guided
      cleavage of transposon-derived transcripts. As many piRNAs also appear to have
      the capacity to target diverse mRNAs, this raises the intriguing possibility that
      piRNAs may act extensively as siRNAs to degrade specific mRNAs. To directly test
      this hypothesis, we compared mouse PIWI (MIWI)-associated piRNAs with
      experimentally identified cleaved mRNA fragments from mouse testes, and observed
      cleavage sites that predominantly occur at position 10 from the 5' end of
      putative targeting piRNAs. We also noted strong biases for U and A residues at
      nucleotide positions 1 and 10, respectively, in both piRNAs and mRNA fragments,
      features that resemble the pattern of piRNA amplification by the 'ping-pong'
      cycle. Through mapping of MIWI-RNA interactions by CLIP-seq and gene expression
      profiling, we found that many potential piRNA-targeted mRNAs directly interact
      with MIWI and show elevated expression levels in the testes of Miwi catalytic
      mutant mice. Reporter-based assays further revealed the importance of base
      pairing between piRNAs and mRNA targets and the requirement for both the slicer
      activity and piRNA-loading ability of MIWI in piRNA-mediated target repression.
      Importantly, we demonstrated that proper turnover of certain key piRNA targets is
      essential for sperm formation. Together, these findings reveal the siRNA-like
      function of the piRNA machinery in mouse testes and its central requirement for
      male germ cell development and maturation. 

PMID- 25582082
TI  - Crystal structures of the Erp protein family members ErpP and ErpC from Borrelia
      burgdorferi reveal the reason for different affinities for complement regulator
      factor H.
AB  - Borrelia burgdorferi is the causative agent of Lyme disease, which can be
      acquired after the bite of an infected Ixodes tick. As a strategy to resist the
      innate immunity and to successfully spread and proliferate, B. burgdorferi
      expresses a set of outer membrane proteins that are capable of binding complement
      regulator factor H (CFH), factor H-like protein 1 (CFHL-1) and factor H-related
      proteins (CFHR) to avoid complement-mediated killing. B. burgdorferi B31 contains
      three proteins that belong to the Erp (OspE/F-related) protein family and are
      capable of binding CFH and some CFHRs, namely ErpA, ErpC and ErpP. We have
      determined the crystal structure of ErpP at 2.53A resolution and the crystal
      structure of ErpC at 2.15A resolution. Recently, the crystal structure of the Erp
      family member OspE from B. burgdorferi N40 was determined in complex with CFH
      domains 19-20, revealing the residues involved in the complex formation. Despite
      the high sequence conservation between ErpA, ErpC, ErpP and the homologous
      protein OspE (78-80%), the affinity for CFH and CFHRs differs markedly among the
      Erp family members, suggesting that ErpC may bind only CFHRs but not CFH. A
      comparison of the binding site in OspE with those of ErpC and ErpP revealed that
      the extended loop region, which is only observed in the potential binding site of
      ErpC, plays an important role by preventing the binding of CFH. These results can
      explain the inability of ErpC to bind CFH, whereas ErpP and ErpA still possess
      the ability to bind CFH. 

PMID- 25582083
TI  - Spatial neuroproteomics using imaging mass spectrometry.
AB  - The nervous system constitutes arguably the most complicated and least understood
      cellular network in the human body. This consequently manifests itself in the
      fact that the molecular bases of neurodegenerative diseases remain unknown. The
      limited understanding of neurobiological mechanisms relates directly to the lack
      of appropriate bioanalytical technologies that allow highly resolved, sensitive,
      specific and comprehensive molecular imaging in complex biological matrices.
      Imaging mass spectrometry (IMS) is an emerging technique for molecular imaging.
      The technique is characterized by its high chemical specificity allowing
      comprehensive, spatial protein and peptide profiling in situ. Imaging MS
      represents therefore a powerful approach for investigation of spatio-temporal
      protein and peptide regulations in CNS derived tissue and cells. This review aims
      to provide a concise overview of major developments and applications concerning
      imaging mass spectrometry based protein and peptide profiling in neurobiological
      and biomedical research. This article is part of a Special Issue entitled:
      Neuroproteomics: Applications in Neuroscience and Neurology. 

PMID- 25582081
TI  - Methods of integrating data to uncover genotype-phenotype interactions.
AB  - Recent technological advances have expanded the breadth of available omic data,
      from whole-genome sequencing data, to extensive transcriptomic, methylomic and
      metabolomic data. A key goal of analyses of these data is the identification of
      effective models that predict phenotypic traits and outcomes, elucidating
      important biomarkers and generating important insights into the genetic
      underpinnings of the heritability of complex traits. There is still a need for
      powerful and advanced analysis strategies to fully harness the utility of these
      comprehensive high-throughput data, identifying true associations and reducing
      the number of false associations. In this Review, we explore the emerging
      approaches for data integration - including meta-dimensional and multi-staged
      analyses - which aim to deepen our understanding of the role of genetics and
      genomics in complex outcomes. With the use and further development of these
      approaches, an improved understanding of the relationship between genomic
      variation and human phenotypes may be revealed. 

PMID- 25582080
TI  - Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2
      receptors and negative prognostic impact of soluble CD25.
AB  - The cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibody ipilimumab
      induces immune-mediated long-term control of metastatic melanoma in a fraction of
      patients. Although ipilimumab undoubtedly exerts its therapeutic effects via
      immunostimulation, thus far clinically useful, immunologically relevant
      biomarkers that predict treatment efficiency have been elusive. Here, we show
      that neutralization of IL-2 or blocking the alpha and beta subunits of the IL-2
      receptor (CD25 and CD122, respectively) abolished the antitumor effects and the
      accompanying improvement of the ratio of intratumoral T effector versus
      regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in
      preclinical mouse models. CTLA-4 blockade led to the reduction of a suppressive
      CD4(+) T cell subset expressing Lag3, ICOS, IL-10 and Egr2 with a concomitant
      rise in IL-2-producing effector cells that lost FoxP3 expression and accumulated
      in regressing tumors. While recombinant IL-2 improved the therapeutic efficacy of
      CTLA-4 blockade, the decoy IL-2 receptor alpha (IL-2Ralpha, sCD25) inhibited the
      anticancer effects of CTLA-4 blockade. In 262 metastatic melanoma patients
      receiving ipilimumab, baseline serum concentrations of sCD25 represented an
      independent indicator of overall survival, with high levels predicting resistance
      to therapy. Altogether, these results unravel a role for IL-2 and IL-2 receptors
      in the anticancer activity of CTLA-4 blockade. Importantly, our study provides
      the first immunologically relevant biomarker, namely elevated serum sCD25, that
      predicts resistance to CTLA-4 blockade in patients with melanoma. 

PMID- 25582084
TI  - A rare case of isolated hydatid cyst of breast.
AB  - INTRODUCTION: Hydatid cyst of the breast is very rare. It is challenging to
      differentiate it from other tumoral lesions of the breast. Only few reports of
      breast hydatid cyst are published and majority of the reported cases have been
      diagnosed postoperatively as it is not possible to reach definitive diagnosis
      with clinical examination and radiological investigations only. PRESENTATION OF
      CASE: A 31-year old woman presented with a painless lump in the right breast
      since one year duration. On clinical examination, a non-mobile, firm lump was
      detected in the right breast associated with nipple retraction, but there was no
      axillary lymphadenopathy. This case was diagnosed as hydatid cyst incidentally
      during surgery from its gross appearance which mimics that of a liver hydatid
      cyst, normally common in this endemic area. DISCUSSION: Hydatid disease is a
      parasitic infection caused by the larval form of Echinococcus granulosus and seen
      endemically among sheep-raising communities. The breast can be a primary site or
      part of a disseminated hydatidosis. It might mimic fibroadenoma, phyllodes
      tumors, chronic abscesses, or even carcinoma. Preoperative diagnosis can be made
      by fine needle aspiration cytology. It also can be diagnosed by radiological or
      serologic means but neither of them is definitive. Surgery is the treatment of
      choice. CONCLUSION: Hydatid cyst of the breast is very uncommon but it should be
      included in differential diagnosis of breast lumps for patients living in endemic
      areas.

PMID- 25582086
TI  - Creating a gold standard surgical procedure: the development and implementation
      of TVT.

PMID- 25582085
TI  - Early hepatic insult in the offspring of obese maternal mice.
AB  - We hypothesized that the maternal obesity initiates metabolic disorders
      associated with oxidative stress in the liver of offspring since early life.
      Mouse's mothers were assigned into 2 groups according to the diet offered (n = 10
      per group): standard chow (SC) or high-fat diet (HF). The results revealed that
      HF offspring had an increase in body mass at day 10 (+25%, P < .05) and in
      glucose levels (+25%, P < .0001). Hepatic triacylglycerol was increased in HF
      offspring at day 1 and day 10 compared with SC offspring (+30%, P < .01 and +40%,
      P < .01) as was hepatic steatosis (+110%, P < .001; +145%, P < .0001). Fatty acid
      synthase was increased in HF offspring at day 1 (+450%, P < .01) and peroxisome
      proliferator activator receptor-gamma was elevated at day 1 and day 10 (+140%, P
      < .01; +2741%, P < .01). Peroxisome proliferator activator receptor-alpha was
      diminished in HF offspring at day 10 compared with SC offspring (-100%, P < .01).
      Moreover, carnitine palmitoyl-CoA transferase-1 was decreased in HF offspring at
      day 1 and day 10 (-80%, P < .01; -60%, P < .05). In the HF offspring (compared
      with the SC offspring), the catalase and the superoxide dismutase were
      significantly lower in both days 1 and 10 (P < .05). In 10-day-old offspring,
      glutathione peroxidase 1 and glutathione reductase were lower in HF offspring
      than in SC offspring (P < .0001). Our findings suggest that the maternal obesity
      in mice induces an early oxidative dysfunction coupled with hepatic steatosis and
      might contribute to progressive liver injury later in life. 

PMID- 25582087
TI  - Radioactive status of seawater in the northwest Pacific more than one year after
      the Fukushima nuclear accident.
AB  - To understand the impact of Fukushima Nuclear Accident(FNA), eight cruises were
      performed from 2011-2014. This paper reports the seawater monitoring results of
      the third cruise, which was conducted in May-June 2012.The northwest Pacific was
      clearly influenced even more than one year after FNA. However, compared to the
      monitoring results of the first and second cruises, which were performed in 2011,
      the seawater radioactivity of the third cruise decreased greatly. The highest
      value and the highest average of (137)Cs and (134)Cs were found in the 200 m
      layer, which suggested that (137)Cs and (134)Cs were most likely transported to a
      depth of 200 m or deeper. At 21.50 degrees N, 125.00 degrees E, (134)Cs was found
      at a depth of 200 m, which is 430 km away from the southernmost point of Taiwan
      Island. The formation and subduction of Subtropical Mode Water is the most
      reasonable explanation for this process. The coastal water of China was not
      impacted by the radioactive pollutants released from the FNA. The radiation
      increments from (137)Cs, (134)Cs and (90)Sr are only one-thousandth to one
      millionth of the screening rate (10 MUGy/h) according to the estimation using
      ERICA tools. 

PMID- 25582088
TI  - Baastrup's disease (kissing spines syndrome): a pictorial review.
AB  - Excessive lordosis is a common finding and may produce mechanical pressure that
      causes repetitive strains of the interspinous ligament with subsequent
      degeneration and collapse. Baastrup's disease (kissing spine syndrome) is a term
      referring to close approximation of adjacent spinous processes due to
      degenerative changes of the spine. Baastrup's disease usually affects the lumbar
      spine, with L4-L5 being the most commonly affected level. There is higher
      occurrence at ages over 70 and no gender predilection. Symptoms include back pain
      with midline distribution that worsens during extension, is relieved during
      flexion and is exaggerated upon finger pressure at the level of interest.
      Diagnosis rests on clinical examination and imaging studies. The hallmark of
      imaging findings is the close approximation and contact of adjacent spinous
      processes, with all the subsequent findings including oedema, cystic lesions,
      sclerosis, flattening and enlargement of the articulating surfaces, bursitis and
      occasionally epidural cysts or midline epidural fibrotic masses. Proposed
      therapies include conservative treatment, percutaneous infiltrations or surgical
      therapies such as excision of the bursa or osteotomy. The purpose of this study
      is to illustrate the spectrum of imaging findings in Baastrup's disease and to
      emphasise upon including the syndrome in the list of potential causes of low-back
      pain. TEACHING POINTS: * Baastrup's disease refers to close approximation of
      adjacent spinous processes. * Diagnosis of Baastrup's disease is verified with
      clinical examination and imaging studies. * Contact of adjacent spinous processes
      results in oedema, sclerosis, flattening and enlargement. * Proposed therapies
      include conservative treatment, percutaneous infiltrations or surgical therapies.

PMID- 25582090
TI  - Interfacial charge-mediated non-volatile magnetoelectric coupling in
      Co0.3Fe0.7/Ba0.6Sr0.4TiO3/Nb:SrTiO3 multiferroic heterostructures.
AB  - The central challenge in realizing non-volatile, E-field manipulation of
      magnetism lies in finding an energy efficient means to switch between the
      distinct magnetic states in a stable and reversible manner. In this work, we
      demonstrate using electrical polarization-induced charge screening to change the
      ground state of magnetic ordering in order to non-volatilely tune magnetic
      properties in ultra-thin Co0.3Fe0.7/Ba0.6Sr0.4TiO3/Nb:SrTiO3 (001) multiferroic
      heterostructures. A robust, voltage-induced, non-volatile manipulation of out-of
      plane magnetic anisotropy up to 40 Oe is demonstrated and confirmed by
      ferromagnetic resonance measurements. This discovery provides a framework for
      realizing charge-sensitive order parameter tuning in ultra-thin multiferroic
      heterostructures, demonstrating great potential for delivering compact,
      lightweight, reconfigurable, and energy-efficient electronic devices.

PMID- 25582089
TI  - Petroselinum crispum has antioxidant properties, protects against DNA damage and
      inhibits proliferation and migration of cancer cells.
AB  - BACKGROUND: Petroselinum crispum (English parsley) is a common herb of the
      Apiaceae family that is cultivated throughout the world and is widely used as a
      seasoning condiment. Studies have shown its potential as a medicinal herb. In
      this study, P. crispum leaf and stem extracts were evaluated for their
      antioxidant properties, protection against DNA damage in normal 3T3-L1 cells, and
      the inhibition of proliferation and migration of the MCF-7 cells. RESULTS: The
      dichloromethane extract of P. crispum exhibited the highest phenolic content
      (42.31 +/- 0.50 mg GAE g(-1) ) and ferric reducing ability (0.360 +/- 0.009 mmol
      g(-1) ) of the various extractions performed. The extract showed DPPH radical
      scavenging activity with an IC50 value of 3310.0 +/- 80.5 ug mL(-1) . Mouse
      fibroblasts (3T3-L1) pre-treated with 400 ug mL(-1) of the extract showed 50.9%
      protection against H2 O2 -induced DNA damage, suggesting its potential in cancer
      prevention. The extract (300 ug mL(-1) ) inhibited H2 O2 -induced MCF-7 cell
      migration by 41% +/- 4%. As cell migration is necessary for metastasis of cancer
      cells, inhibition of migration is an indication of protection against metastasis.
      CONCLUSION: Petroselinum crispum has health-promoting properties with the
      potential to prevent oxidative stress-related diseases and can be developed into
      functional food.

PMID- 25582091
TI  - Protocol for the evaluation of a quality-based pay for performance scheme in
      Liberia.
AB  - BACKGROUND: Improving the quality of care at hospitals is a key next step in
      rebuilding Liberia's health system. In order to improve the efficiency,
      effectiveness, and quality of care at the secondary hospital level, the country
      is developing a system to upgrade health worker skills and competencies, and
      shifting towards improved provider accountability for results, including a
      Graduate Medical Residency Program (GMRP) and provider accountability for
      improvements in quality through performance-based financing (PBF) at the hospital
      level. METHODS/DESIGN: This document outlines the protocol for the impact
      evaluation of the hospital improvement program. The evaluation will provide an
      estimate of the impact of the project and investigate the mechanism for success
      in a way that can provide general lessons about the quality of health care in low
      income countries. The evaluation aims 1) to provide the best possible estimate of
      program impact and 2) to quantitatively describe the changes that took place
      within facilities as a result of the program. In particular, the impact
      evaluation focuses on the changes in human resources within the hospitals. As
      such, we use a three-period intensive evaluation of treated and matched
      comparison hospitals to see how services change in treated hospitals as well as a
      continuous data collection effort to track the activities of individual health
      workers within treated hospitals. DISCUSSION: We are particularly interested in
      understanding how facilities met quality targets. Did they bring in new health
      workers with higher qualifications? Did they improve the knowledge or competence
      of their existing staff? Did they improve the availability of medicines and
      equipment so that the capacities of existing health workers were improved? Did
      they address the motivation of health workers so that individuals with the same
      competence and capacity were able to provide higher quality? And, if they did
      improve quality, did patients notice?

PMID- 25582092
TI  - On the antibacterial mechanism of graphene oxide (GO) Langmuir-Blodgett films.
AB  - The Langmuir-Blodgett (LB) technique was used to immobilize flat graphene oxide
      (GO) sheets on a PET substrate to ascertain as to whether the edges of GO play an
      integral part in its antimicrobial mechanism. The observed antibacterial activity
      suggests that contact with the edges is not a fundamental part of the mechanism. 

PMID- 25582093
TI  - Occurrence of fenestral diaphragms and knots in renal glomerular endothelia of
      diabetic mutant MafA-/-MafK+ mice as revealed in embedment-free transmission
      electron microscopy.
AB  - Using the advantages (high contrast and transparency and efficient 3D viewing) of
      embedment-free section transmission electron microscopy (TEM), the occurrence of
      numerous fenestral diaphragms was clearly shown in 3D en-face viewing of the
      renal glomerular capillary endothelium of severe overt diabetes mellitus mice,
      which were generally MafA-deficient and simultaneously MafK-overexpressed
      specifically in pancreatic beta-cells. This presents another example of nephritis
      induced diaphragmed fenestrae in the renal glomerular endothelium. In addition,
      knot-/umbilicus-like structures discrete from and larger than the central knots
      of regular diaphragms of fenestrated endothelium were clearly demonstrated to
      occur randomly in the renal glomerular endothelial fenestrae of mutant mice and
      wild ones. The knot-structures were revealed to be protrusions of underlining
      basement lamina in conventional TEM by section-tilting observation.

PMID- 25582095
TI  - Photochromism in sound-induced alignment of a diarylethene supramolecular
      nanofibre.
AB  - A photochromic supramolecular nanofibre, composed of a diarylethene derivative,
      exhibits hydrodynamic alignment upon exposure to the audible sound. The aligned
      nanofibre outputs linear dichroism (LD), whose wavelength region can be switched
      reversibly with UV and visible light. 

PMID- 25582094
TI  - An in vivo detection system for transient and low-abundant protein interactions
      and their kinetics in budding yeast.
AB  - Methylation tracking (M-Track) is a protein-proximity assay in Saccharomyces
      cerevisiae, allowing the detection of transient protein-protein interactions in
      living cells. The bait protein is fused to a histone lysine methyl transferase
      and the prey protein to a methylation acceptor peptide derived from histone 3.
      Upon interaction, the histone 3 fragment is stably methylated on lysine 9 and can
      be detected by methylation-specific antibodies. Since methylation marking is
      irreversible in budding yeast and only takes place in living cells, the
      occurrence of artifacts during cell lysate preparation is greatly reduced,
      leading to a more accurate representation of native interactions. So far, this
      method has been limited to highly abundant or overexpressed proteins. However,
      many proteins of interest are low-abundant, and overexpression of proteins may
      interfere with their function, leading to an artificial situation. Here we report
      the generation of a toolbox including a novel cleavage-enrichment system for the
      analysis of very low-abundant proteins at their native expression levels. In
      addition, we developed a system for the parallel analysis of two prey proteins in
      a single cell, as well as an inducible methylation system. The inducible system
      allows precise control over the time during which the interaction is detected and
      can be used to determine interaction kinetics. Furthermore, we generated a set of
      constructs facilitating the cloning-free genomic tagging of proteins at their
      endogenous locus by homologous recombination, and their expression from
      centromeric plasmids.

PMID- 25582096
TI  - Intermittent preventive antimalarial treatment for children with anaemia.
AB  - BACKGROUND: Anaemia is a global public health problem. Children under five years
      of age living in developing countries (mostly Africa and South-East Asia) are
      highly affected. Although the causes for anaemia are multifactorial, malaria has
      been linked to anaemia in children living in malaria-endemic areas. Administering
      intermittent preventive antimalarial treatment (IPT) to children might reduce
      anaemia, since it could protect children from new Plasmodium parasite infection
      (the parasites that cause malaria) and allow their haemoglobin levels to recover.
      OBJECTIVES: To assess the effect of IPT for children with anaemia living in
      malaria-endemic areas. SEARCH METHODS: We searched the Cochrane Infectious
      Diseases Group Specialized Register, Cochrane Central of Controlled Trials
      (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; and LILACS. We
      also searched the World Health Organization (WHO) International Clinical Trial
      Registry Platform and metaRegister of Controlled Trials (mRCT) for ongoing trials
      up to 4 December 2014. SELECTION CRITERIA: Randomized controlled trials (RCTs)
      evaluating the effect of IPT on children with anaemia. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted data and assessed risk of
      bias. We analysed data by conducting meta-analyses, stratifying data according to
      whether participants received iron supplements or not. We used GRADE to assess
      the quality of evidence. MAIN RESULTS: Six trials with 3847 participants met our
      inclusion criteria. Trials were conducted in areas of low malaria endemicity
      (three trials), and moderate to high endemicity (three trials). Four trials were
      in areas of seasonal malaria transmission. Iron was given to all children in two
      trials, and evaluated in a factorial design in a further two trials.IPT for
      children with anaemia probably has little or no effect on the proportion anaemic
      at 12 weeks follow-up (four trials, 2237 participants, (moderate quality
      evidence).IPT in anaemic children probably increases the mean change in
      haemoglobin levels from baseline to follow-up at 12 weeks on average by 0.32 g/dL
      (MD 0.32, 95% CI 0.19 to 0.45; four trials, 1672 participants, moderate quality
      evidence); and may improve haemoglobin levels at 12 weeks (MD 0.35, 95% CI 0.06
      to 0.64; four trials, 1672 participants, low quality evidence). For both of these
      outcomes, subgroup analysis did not demonstrate a difference between children
      receiving iron and those that did not.IPT for children with anaemia probably has
      little or no effect on mortality or hospital admissions at six months (three
      trials, 3160 participants moderate quality evidence). Subgroup analysis did not
      show a difference between those children receiving iron supplements and those
      that did not. AUTHORS' CONCLUSIONS: Trials did show a small effect on average
      haemoglobin levels but this did not appear to translate into an effect on
      mortality and hospital admissions. Three of the six trials were conducted in low
      endemicity areas where transmission is low and thus any protective effect is
      likely to be modest.

PMID- 25582097
TI  - Mobile application for information on reversible contraception: a randomized
      controlled trial.
AB  - OBJECTIVE: Due to time constraints that limit physician's ability to deliver
      detailed contraception counseling, patients increasingly require supplemental
      education opportunities. Applications for smartphones and tablets are being
      designed to educate patients about contraceptive methods and simplify
      communication between patient and provider. We designed a mobile application
      entitled Plan A Birth Control to provide targeted information about the 10 most
      common, nonpermanent contraceptive methods with emphasis on long-acting
      reversible methods. STUDY DESIGN: We developed a mobile application designed to
      provide tailored information about the 10 most common nonpermanent contraceptive
      methods. After pilot testing with 40 volunteers from the clinic, 120 participants
      were recruited for a randomized controlled trial. (ClinicalTrials.gov identifier:
      NCT02234271) Participants were assigned by simple randomization to contraception
      counseling via tablet or health educator. We compared participants' contraceptive
      choice between the 2 groups. Secondary outcomes included knowledge of the method
      of choice and satisfaction with counseling. RESULTS: Of the 120 participants in
      the primary study, 65 chose long-acting reversible methods. The uptake of long
      acting reversible contraceptives was similar between the groups (34 received
      health educator counseling and 31 received mobile application counseling). Both
      groups were demographically similar in age and educational status. Knowledge of
      long-acting methods did not differ significantly between the groups (P = .30).
      CONCLUSION: Results from our study suggest that Plan A Birth Control did not
      adversely affect highly effective birth control uptake in our study population.
      This can save time for physicians and health educators if used as an adjunct to
      contraception counseling in waiting room settings.

PMID- 25582099
TI  - Recurrence of high-grade cervical abnormalities following conservative management
      of cervical intraepithelial neoplasia grade 2.
AB  - OBJECTIVE: Conservative management of cervical intraepithelial neoplasia (CIN)
      grade 2 in women younger than 25 years may reduce overtreatment. However, long
      term efficacy remains uncertain. This retrospective cohort study aimed to
      determine the rate of recurrence of high-grade abnormalities among young women
      with a history of CIN 2 that spontaneously regressed within 2 years and compare
      this with the rate of high-grade abnormality in similar women with an initial
      diagnosis of CIN 1. STUDY DESIGN: We identified all women aged younger than 25
      years who were diagnosed with CIN 1 or CIN 2 between January 2005 and August 2009
      within 2 colposcopy units. Follow-up data from the National Cervical Screening
      Programme were obtained to identify those women who developed recurrent high
      grade lesions before October 2012. Comparisons were made using Cox proportional
      hazards regression. RESULTS: A total of 683 women were included: 106 with CIN 2
      that spontaneously regressed, 299 with treated CIN 2, and 278 with conservatively
      managed CIN 1. Median follow-up was 4 years. There was no significant difference
      in the risk of development of high-grade abnormalities after 2 years between the
      spontaneously regressing CIN 2 and CIN 1 groups (P = .83). Women with treated CIN
      2 had a significantly lower risk of recurrence than women with untreated CIN 2 (P
      = .01). CONCLUSION: CIN 2 that has spontaneously regressed appears to behave as a
      low-grade lesion. This study contributes to the growing body of evidence that
      careful observation of CIN 2 is an efficacious and appropriate initial management
      option for women aged younger than 25 years at diagnosis.

PMID- 25582098
TI  - Recurrence of hypertensive disorders of pregnancy: an individual patient data
      metaanalysis.
AB  - OBJECTIVE: We performed an individual participant data (IPD) metaanalysis to
      calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and
      recurrence of individual hypertensive syndromes. STUDY DESIGN: We performed an
      electronic literature search for cohort studies that reported on women
      experiencing HDP and who had a subsequent pregnancy. The principal investigators
      were contacted and informed of our study; we requested their original study data.
      The data were merged to form one combined database. The results will be presented
      as percentages with 95% confidence interval (CI) and odds ratios with 95% CI.
      RESULTS: Of 94 eligible cohort studies, we obtained IPD of 22 studies, including
      a total of 99,415 women. Pooled data of 64 studies that used published data (IPD
      where available) showed a recurrence rate of 18.1% (n=152,213; 95% CI, 17.9
      18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a
      HDP was 20.7% (95% CI, 20.4-20.9%). Recurrence manifested as preeclampsia in
      13.8% of the studies (95% CI,13.6-14.1%), gestational hypertension in 8.6% of the
      studies (95% CI, 8.4-8.8%) and hemolysis, elevated liver enzymes and low
      platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16-0.25%). The
      delivery of a small-for-gestational-age child accompanied the recurrent HDP in
      3.4% of the studies (95% CI, 3.2-3.6%). Concomitant HELLP syndrome or delivery of
      a small-for-gestational-age child increased the risk of recurrence of HDP.
      Recurrence increased with decreasing gestational age at delivery in the index
      pregnancy. If the HDP recurred, in general it was milder, regarding maximum
      diastolic blood pressure, proteinuria, the use of oral antihypertensive and
      anticonvulsive medication, the delivery of a small-for-gestational-age child,
      premature delivery, and perinatal death. Normotensive women experienced chronic
      hypertension after pregnancy more often after experiencing recurrence (odds
      ratio, 3.7; 95% CI, 2.3-6.1). CONCLUSION: Among women that experience
      hypertension in pregnancy, the recurrence rate in a next pregnancy is relatively
      low, and the course of disease is milder for most women with recurrent disease.
      These reassuring data should be used for shared decision-making in women who
      consider a new pregnancy after a pregnancy that was complicated by hypertension.

PMID- 25582100
TI  - Single- vs double-layer and locking vs nonlocking closure of uterus: missing
      woods for the trees?

PMID- 25582102
TI  - Reply: To PMID 24912096.

PMID- 25582101
TI  - A critical assessment of morcellation and its impact on gynecologic surgery and
      the limitations of the existing literature.
AB  - Uterine sarcomas are rare uterine malignancies that are difficult to diagnose
      preoperatively. Because of cases of disseminated sarcoma after laparoscopic
      hysterectomy, the role of power morcellators in gynecologic surgery has been
      questioned. Morcellation is an integral part of making laparoscopic surgery
      possible for the removal of large uterine leiomyomata, and the development of
      power morcellation has increased efficiency during these procedures. Minimally
      invasive surgery has demonstrated benefits that include improved pain control,
      decreased infection risk, and faster surgical recovery and return to work. In
      this review, we examine the risk of incidental sarcoma at the time of surgery,
      the quality of the data, the accuracy of clinical and radiologic predictors of
      uterine sarcoma, and the impact of morcellation on the prognosis of uterine
      sarcoma. 

PMID- 25582103
TI  - The potential perinatal origin of placentation disorders in the young
      primigravida.
AB  - The fetus is exposed to high plasma concentrations of unbound estrogens and
      progesterone throughout pregnancy. However, secretory or decidual changes in the
      fetal uterus occur relatively infrequently before birth, suggesting a variable
      endometrial progesterone response at the time of birth. Arguably, partial
      progesterone resistance that persists into adolescent years may compromise the
      physiological transformation of the spiral arteries and predispose for defective
      placentation in the case of pregnancy. Decidualization of the endometrial stromal
      compartment and junctional zone myometrium precedes trophoblast invasion. It
      represents the first step in the process of spiral artery remodeling needed to
      establish effective uteroplacental blood flow by midpregnancy. The major
      obstetric syndromes caused by impaired placental bed spiral artery remodeling are
      prevalent in teenage pregnancies, including preeclampsia, fetal growth
      restriction, and spontaneous preterm labor. Preconditioning of the uterus in
      response to cyclic menstruation during adolescence may be critical to achieve
      full uterine responsiveness to hormonal cues. Understanding the mechanisms of
      functional maturation of the uterus during the early reproductive years may yield
      novel insights into the major obstetric syndromes. 

PMID- 25582106
TI  - A novel Prins cascade process for the stereoselective synthesis of oxa-bicycles.
AB  - E- and Z-9-Methyldeca-3,8-dien-1-ols undergo smooth cyclization with aldehydes in
      the presence of 20 mol% AgSbF6 under extremely mild conditions to generate the
      corresponding oxa-bicycles in good yields with excellent selectivity. In fact, E
      olefin affords the trans-product exclusively, whereas the Z-olefin gives the cis
      product predominantly. In the case of E- or Z-8-methylnona-3,8-dien-1-ol, the
      product is formed via the termination of Prins cyclization with an allylic C-H
      bond through olefin migration. The termination of Prins cyclization with tethered
      olefin is an unprecedented reaction, which provides a useful motif of various
      natural products. 

PMID- 25582109
TI  - Peptide-based materials for nanomedicine.

PMID- 25582104
TI  - Second-line uterotonics and the risk of hemorrhage-related morbidity.
AB  - OBJECTIVE: Uterine atony is a leading cause of postpartum hemorrhage. Although
      most cases of postpartum hemorrhage respond to first-line therapy with uterine
      massage and oxytocin administration, second-line uterotonics including
      methylergonovine and carboprost are integral for the management of refractory
      uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of
      hemorrhage-related morbidity differs in women exposed to methylergonovine or
      carboprost at cesarean delivery. STUDY DESIGN: We performed a secondary analysis
      using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified
      women who underwent cesarean delivery and received either methylergonovine or
      carboprost for refractory uterine atony. The primary outcome was hemorrhage
      related morbidity defined as intraoperative or postoperative red blood cell
      transfusion or the need for additional surgical interventions including uterine
      artery ligation, hypogastric artery ligation, or peripartum hysterectomy for
      atony. We compared the risk of hemorrhage-related morbidity in those exposed to
      methylergonovine vs carboprost. Propensity-score matching was used to account for
      potential confounders. RESULTS: The study cohort comprised 1335 women; 870
      (65.2%) women received methylergonovine and 465 (34.8%) women received
      carboprost. After accounting for potential confounders, the risk of hemorrhage
      related morbidity was higher in the carboprost group than the methylergonovine
      group (relative risk, 1.7; 95% confidence interval, 1.2-2.6). CONCLUSION: In this
      propensity score-matched analysis, methylergonovine was associated with reduced
      risk of hemorrhage-related morbidity during cesarean delivery compared to
      carboprost. Based on these results, methylergonovine may be a more effective
      second-line uterotonic.

PMID- 25582105
TI  - Invariant NKT cells promote alcohol-induced steatohepatitis through interleukin
      1beta in mice.
AB  - BACKGROUND & AIMS: It was reported that alcohol consumption activated the NLRP3
      inflammasome in Kupffer cells, leading to mature interleukin (IL)-1beta release
      in alcoholic liver injury; however, how IL-1beta promotes liver injury remains
      unclear. METHODS: We investigated the role of IL-1beta in alcoholic
      steatohepatitis by using a chronic plus single-binge ethanol consumption mouse
      model. RESULTS: Here, liver steatosis was accompanied by notably increased
      invariant natural killer T (iNKT) cell numbers and activation, and iNKT-deficient
      Jalpha18(-/-) mice developed less alcohol-induced steatosis, with reduced liver
      inflammation and neutrophil infiltration. Kupffer cells and IL-1beta were
      required for the hepatic iNKT accumulation, as either blocking IL-1beta signaling
      with a recombinant IL-1 receptor antagonist (IL-1Ra), depleting Kupffer cells by
      clodronate liposomes, or specifically silencing IL-1beta in Kupffer cells by
      nanoparticle-encapsulated siRNA, resulted in inhibited hepatic iNKT cell
      accumulation and activation, as well as amelioration of alcoholic fatty liver. In
      addition, IL-1beta overexpression in hepatocytes was sufficient to compensate for
      Kupffer cell depletion. Increased gene and protein expression of mature IL-1beta
      correlated with elevated expression of the NLRP3 inflammasome components NLRP3,
      ASC, and cleaved caspase-1 in Kupffer cells from ethanol-exposed wild-type mice.
      NLRP3 deficiency led to the attenuation of alcoholic steatosis, similarly as
      Kupffer cell depletion, almost without hepatic NKT cells. CONCLUSIONS: After
      alcohol-exposure Kupffer cell-derived IL-1beta triggered by NLRP3 activation,
      recruits and activates hepatic iNKT cells, subsequently promoting liver
      inflammation and neutrophil infiltration, and inducing alcoholic liver injury.

PMID- 25582112
TI  - Enhanced contact endoscopy for the detection of neoangiogenesis in tumors of the
      larynx and hypopharynx.
AB  - OBJECTIVES/HYPOTHESIS: Image-enhanced endoscopy, such as narrow band imaging and
      the Storz Professional Image Enhancement System, have been increasingly used in
      patients with suspect lesions of the larynx and hypopharynx during preoperative
      and intraoperative assessment. STUDY DESIGN: In the present study, a contact
      endoscope was coupled with the systems of image-enhanced endoscopy, as to
      precisely distinguish the peculiar neoangiogenetic changes in inflammation, and
      precancerous and cancerous lesions of the larynx and hypopharynx. METHODS: We
      performed a single-blind study with this original approach of a series of 44
      patients with different lesions of the larynx and hypopharynx. RESULTS: We
      observed five obvious vascular patterns matching the diagnosis in 41 patients out
      of 44, with accuracy in the differential diagnosis between normal tissue and
      hyperplasia versus mild dysplasia and carcinoma of 97.6%. CONCLUSIONS: Enhanced
      contact endoscopy allows for predicting histologic changes of laryngeal and
      hypopharyngeal lesions from inflammation to cancer on based on fine evaluation of
      the neoangiogenetic changes of the chorion. This innovative procedure can be
      considered an important tool during diagnosis, treatment, and follow-up of
      patients with precancer and cancer of the larynx and hypopharynx.

PMID- 25582114
TI  - Responses of the hepatic glutathione antioxidant defense system and related gene
      expression in juvenile common carp after chronic treatment with tributyltin.
AB  - Recently, residual organotin compounds have generally been recognised as relevant
      sources of aquatic environmental pollutants. However, the effects of these
      contaminants on the glutathione (GSH)-antioxidant system of fishes have not been
      adequately studied. In the current study, the chronic effects of tributyltin
      (TBT) found within antifouling paints for ships, on the GSH antioxidant system
      and related gene expression in the liver of juvenile common carp (Cyprinus
      carpio) were investigated. Fishes were exposed to sub-lethal concentrations of
      TBT (75 ng/L, 0.75 and 7.5 MUg/L) for 15, 30 and 60 days. GSH levels and GSH
      related enzymes activities, including glutathione peroxidase (GPx), glutathione
      reductase (GR) and glutathione S-transferase (GST), were quantified in the fish
      liver. The levels of malondialdehyde were also measured as a marker of oxidative
      damage. In addition, the expression levels of gstp1, gr and gpx1 in common carp
      chronically exposed to TBT were determined. The results of the current study
      indicate that chronic exposure of TBT results in reactive oxygen species stress
      in the liver of common carp, and mRNA expression levels are more sensitive than
      related enzyme levels. In short, the measured GSH-related indices could
      potentially be used as molecular indicators for monitoring organotin compounds in
      the aquatic environment. 

PMID- 25582113
TI  - The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides
      effective tumor control in human lung cancer cells.
AB  - Hsp90 inhibitors have become well-studied antitumor agents for their selective
      property against tumors versus normal cells. The combined treatment of Hsp90
      inhibitor and conventional photon radiation also showed more effective tumor
      growth delay than radiation alone. However, little is known regarding the
      combined treatment of Hsp90 inhibitor and heavy-ion irradiation. In this study,
      SQ5 human lung tumor cells were used in vitro for clonogenic cell survival and in
      vivo for tumor growth delay measurement using a mouse xenograft model after 17
      allylamino-17-demethoxygeldanamycin (17AAG) pretreatment and carbon ion
      irradiation. Repair of DNA double strand breaks (DSBs) was also assessed along
      with expressions of DSB repair-related proteins. Cell cycle analysis after the
      combined treatment was also performed. The combined treatment of 17AAG and carbon
      ions revealed a promising treatment option in both in vitro and in vivo studies.
      One likely cause of this effectiveness was shown to be the inhibition of
      homologous recombination repair by 17AAG. The more intensified G2 cell cycle
      delay was also associated with the combined treatment when compared with carbon
      ion treatment alone. Our findings indicate that the combination of Hsp90
      inhibition and heavy-ion irradiation provides a new effective therapeutic
      alternative for treatment of solid tumors. 

PMID- 25582116
TI  - The strategy does not matter: Effects of acceptance, reappraisal, and distraction
      on the course of anticipatory anxiety in social anxiety disorder.
AB  - OBJECTIVES: Anticipatory anxiety is a core feature of social anxiety disorder
      (SAD); however, there is a paucity of data on effective strategies for dealing
      with this affective state. The present study examined the effects of reappraisal,
      acceptance, and distraction on the course of anticipatory anxiety. DESIGN: The
      study used an experimental design, randomly assigning participants to one of
      three strategy groups. Participants were instructed to employ these strategies
      during the anticipation of an impromptu speech. METHODS: Participants with SAD (n
      = 67) and healthy controls (n = 72) were compared with regard to their ability to
      adopt the prescribed strategies and with regard to the effects of strategy use on
      self-reported and psychophysiological markers of arousal. RESULTS: SAD
      participants reported more problems in adopting the assigned strategies than
      controls, although the time spent with each strategy did not differ by group. In
      both groups, acceptance was rated as more difficult to adopt than reappraisal and
      distraction. Subjective ratings of anxiety decreased during the first 10 min of
      anticipation regardless of diagnostic group or strategy, but anxiety increased
      again immediately prior to the speech. Psychophysiological parameters were
      largely unaffected by group or strategy. CONCLUSION: The results question whether
      there are differential benefits of different emotion regulation (ER) strategies
      in dealing with anticipatory anxiety. The observed rebound of anxiety prior to
      the social event calls into doubt the long-term effectiveness of these
      strategies, at least during the regulation of anticipatory anxiety. PRACTITIONER
      POINTS: Coping with anticipatory anxiety is an important issue in treating SAD.
      Compared to healthy controls, individuals diagnosed with SAD experienced more
      problems in adopting prescribed ER strategies for dealing with anticipatory
      anxiety. We found no differences between acceptance, reappraisal, and
      distraction, calling into question that one strategy should be generally
      recommended by clinicians.

PMID- 25582115
TI  - Diagnosis and imaging of orbital roof fractures: a review of the current
      literature.
AB  - Isolated adult orbital roof fractures are uncommon, and the majority of them are
      typically associated with extensive craniofacial, ophthalmologic, and other body
      injuries. It is crucial to make an appropriate diagnosis of orbital roof fracture
      if present. Therefore, the aim of this article was to review the current
      literature about diagnosis and imaging of orbital roof fracture to obtain current
      indications. A systematic review of articles published between January 1990 and
      August 2013 was performed. Early diagnosis of orbital roof fractures can reduce
      the incidences of intracranial and ocular complications. CT scan still plays a
      major role in the assessment of acute orbital trauma. Careful assessment and
      reporting of the CT scan findings are important. In fact, the clinicians managing
      the patient with acute head and facial trauma should be familiar with the common
      findings of CT scan in case of an orbital roof fracture. 

PMID- 25582117
TI  - Contamination and release of nanomaterials associated with the use of personal
      protective clothing.
AB  - INTRODUCTION: We investigated nanomaterial release associated with the
      contamination of protective clothing during manipulation of clothing fabrics
      contaminated with nanoparticles. Nanomaterials, when released as airborne
      nanoparticles, can cause inhalation exposure which is the route of exposure of
      most concern to cause adverse health effects. Measurement of such nanoparticle re
      suspension has not yet been conducted. Protective clothing can be contaminated
      with airborne nanoparticles during handling and operating processes, typically on
      the arms and front of the body. The contaminated clothing could release
      nanoparticles in the general room while performing other activities and
      manipulating the clothing after work. METHODS: The exposures associated with
      three different fabric materials of contaminated laboratory coats (cotton,
      polyester, and Tyvek), including the magnitude of contamination and particle
      release, were investigated in this study by measuring the number concentration
      increase and the weight change on fabric pieces. This study simulated real life
      occupational exposure scenarios and was performed in both regular and clean room
      environments to investigate the effect of background aerosols on the
      measurements. Concentration were measured using particle spectrometers for
      diameters from 10nm to 10 um. Collected aerosol particles and contaminated fabric
      surfaces were characterized using scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), and elemental composition analysis.
      RESULTS: The magnitude of particle release from contaminated lab coat fabric was
      found to vary by the type of fabric material; cotton fabric showed the highest
      level of contamination and particle release, followed by Tyvek and polyester
      fabrics. The polyester lab coat material was found to have the lowest particle
      release to deposition (R/D) ratio. The particle release number concentrations
      were in a range of 768-119 particles cm(-3) and 586-187 particles cm(-3) in
      regular and clean rooms, respectively. Multiple peaks were observed in the number
      concentration distribution data, with particle diameters peaking at 40-50 and 100
      300nm. CONCLUSIONS: The SEM analysis of the contaminated fabric surface found
      test particles and other environmental particles. The elemental composition
      analysis presented detectable response to the studied alumina oxide particles.
      The laboratory coat primarily made of cotton woven material is not recommended
      for worker protection against nanoparticle exposure because of the highest
      particle contamination and release ability. In addition, the result demonstrated
      that a well-controlled (cleanroom) environment is critical to investigate the
      factors affecting nanoparticle interaction with protective clothing.

PMID- 25582118
TI  - Social Supports as Enabling Factors in Nursing Home Admissions: Rural, Suburban,
      and Urban Differences.
AB  - This study investigates differences in social support and nursing home admission
      by rurality of residence. We use discrete-time event history models with
      longitudinal data from seven waves (1998-2010) of the Health and Retirement Study
      to prospectively examine the risk of spending 30 or more days in a nursing home
      (n = 5,913). Results show that elders with a health problem who live in rural
      areas of the South or Midwest have approximately 2 times higher odds of nursing
      home entry than elders living in urban areas in the Northeast. Rural elders
      report somewhat higher social support than non-rural elders, and controlling for
      these forms of social support does not explain the higher risk of a nursing home
      stay for Southerners and Midwesterners living in rural areas. Results suggest
      that social support has a similar association with nursing home entry for rural,
      suburban, and urban elders.

PMID- 25582119
TI  - Government proposes changes to hospital doctors' overtime.

PMID- 25582121
TI  - Impact of renal function on survival after transcatheter aortic valve
      implantation (TAVI): an analysis of the UK TAVI registry.
AB  - OBJECTIVE: To determine the nature of the association between renal dysfunction
      and outcomes following transcatheter aortic valve implantation (TAVI) in all
      cases performed in the UK between 2007 and 2012. METHODS: The UK TAVI registry
      was established to report outcomes on all TAVI procedures performed within the
      UK. Data were collected prospectively on 3980 patients from 1 January 2007 until
      31 December 2012. RESULTS: In total, 205 patients (5.5%) died during their
      admission. Moderate to advanced chronic kidney disease (CKD) (estimated
      glomerular filtration rate (eGFR) <45 mL/min/1.73 m(2)) was significantly
      associated with increased mortality, even after adjustment for risk factors (OR
      1.45, 95% CI 1.03 to 2.05; p=0.04). For every 10 mL/min/1.73 m(2) decrease in
      eGFR, in-hospital mortality increased by 8.2% (95% CI 1.1% to 14.7%; p=0.03). In
      total 1119 patients (30.2%) died during the follow-up period (median 543 days).
      Moderate to advanced CKD (eGFR <45 mL/min/1.73 m(2)) was significantly associated
      with increased mortality, even after adjustment for risk factors (OR 1.36, 95% CI
      1.17 to 1.58; p<0.001). For every 10 mL/min/1.73 m(2) decrease in eGFR,
      cumulative mortality increased by 4.4% (95% CI 1.2% to 7.5%; p=0.007).
      Preoperative kidney function and the need for preoperative dialysis treatment
      discriminated between patients who died and survived. However, predictive power
      was poor with none of the c-statistics being >0.6. CONCLUSIONS: Pre-procedural
      renal dysfunction is associated, in a graded fashion independently of dialysis
      status, with worse outcomes, including mortality in patients undergoing TAVI.

PMID- 25582122
TI  - Oxygen consumption in children and adults with congenital and acquired heart
      disease: the quest for better estimates.

PMID- 25582123
TI  - Synthesis of benzofuro[3,2-b]pyridines via palladium-catalyzed dual C-H
      activation of 3-phenoxypyridine 1-oxides.
AB  - An efficient oxidative cyclization to straightforward synthesis of benzofuro[3,2
      b]pyridine 1-oxides with high regioselectivity via Pd-catalyzed intramolecular
      dual C-H activation was developed. The resulting products could be deoxygenated
      easily to the corresponding benzofuro[3,2-b]pyridines in excellent yields. 

PMID- 25582120
TI  - BRCA1 and CtIP promote alternative non-homologous end-joining at uncapped
      telomeres.
AB  - Loss of telomere protection occurs during physiological cell senescence and
      ageing, due to attrition of telomeric repeats and insufficient retention of the
      telomere-binding factor TRF2. Subsequently formed telomere fusions trigger
      rampant genomic instability leading to cell death or tumorigenesis.
      Mechanistically, telomere fusions require either the classical non-homologous end
      joining (C-NHEJ) pathway dependent on Ku70/80 and LIG4, or the alternative non
      homologous end-joining (A-NHEJ), which relies on PARP1 and LIG3. Here, we show
      that the tumour suppressor BRCA1, together with its interacting partner CtIP,
      both acting in end resection, also promotes end-joining of uncapped telomeres.
      BRCA1 and CtIP do not function in the ATM-dependent telomere damage signalling,
      nor in telomere overhang removal, which are critical for telomere fusions by C
      NHEJ. Instead, BRCA1 and CtIP act in the same pathway as LIG3 to promote joining
      of de-protected telomeres by A-NHEJ. Our work therefore ascribes novel roles for
      BRCA1 and CtIP in end-processing and fusion reactions at uncapped telomeres,
      underlining the complexity of DNA repair pathways that act at chromosome ends
      lacking protective structures. Moreover, A-NHEJ provides a mechanism of
      previously unanticipated significance in telomere dysfunction-induced genome
      instability. 

PMID- 25582124
TI  - Impedimetric toxicity assay in microfluidics using free and liposome-encapsulated
      anticancer drugs.
AB  - In this work, we have developed a microfluidic cytotoxicity assay for a cell
      culture and detection platform, which enables both fluid handling and
      electrochemical/optical detection. The cytotoxic effect of anticancer drugs
      doxorubicin (DOX), oxaliplatin (OX) as well as OX-loaded liposomes, developed for
      targeted drug delivery, was evaluated using real-time impedance monitoring. The
      time-dependent effect of DOX on HeLa cells was monitored and found to have a
      delayed onset of cytotoxicity in microfluidics compared with static culture
      conditions based on data obtained in our previous study. The result of a
      fluorescent microscopic annexin V/propidium iodide assay, performed in
      microfluidics, confirmed the outcome of the real-time impedance assay. In
      addition, the response of HeLa cells to OX-induced cytotoxicity proved to be
      slower than toxicity induced by DOX. A difference in the time-dependent cytotoxic
      response of fibrosarcoma cells (HT1080) to free OX and OX-loaded liposomes was
      observed and attributed to incomplete degradation of the liposomes, which results
      in lower drug availability. The matrix metalloproteinase (MMP)-dependent release
      of OX from OX-loaded liposomes was also confirmed using laryngopharynx carcinoma
      cells (FaDu). The comparison and the observed differences between the cytotoxic
      effects under microfluidic and static conditions highlight the importance of
      comparative studies as basis for implementation of microfluidic cytotoxic assays.

PMID- 25582126
TI  - The shape of ibuprofen in the gas phase.
AB  - Ibuprofen's pain-relieving properties arise from its ability to physically block
      the active site of an enzyme, thus making its structural and conformational
      properties highly interesting. We here present a conformer-selective high
      resolution broadband rotational spectroscopy study of gas-phase ibuprofen. The
      interpretation of the spectroscopic results is supported by quantum-chemical
      calculations. We identify four low-energy conformers that differ in the
      structural arrangement of the isobutyl moiety with respect to the remainder of
      the molecule. While the isobutyl group shows high structural flexibility -
      resulting in distinct low-energy conformers - the propanoic acid group favors a
      stable arrangement. 

PMID- 25582127
TI  - Changes and titles.

PMID- 25582125
TI  - Molecular identification and characterization of Trichinella spiralis proteasome
      subunit beta type-7.
AB  - BACKGROUND: Previous study showed that Trichinella spiralis proteasome subunit
      beta type-7 (Tspst) gene is an up-regulated gene in intestinal infective larvae
      (IIL) compared to muscle larvae (ML), which was screened by using suppression
      subtractive hybridization (SSH) and confirmed by real-time PCR. Tspst may be
      related to the larval invasion of intestinal epithelial cells (IECs). The aim of
      this study was to identify Tspst and to investigate its immune protection against
      intestinal T. spiralis infection. METHODS: The Tspst gene encoding a 29 kDa
      protein from T. spiralis infective larvae was cloned, and recombinant Tspst
      protein (rTspst) was produced in an Escherichia coli expression system. The
      rTspst was used to immunize BALB/c mice. Anti-rTspst antibodies were used to
      determine the immunolocolization of Tspst in the parasite. Transcription and
      expression of Tspst at T. spiralis different developmental stages were observed
      by RT-PCR and immunofluorescence test (IFT). The in vitro or in vivo immune
      protection of anti-rTspst serum or rTspst against intestinal T. spiralis
      infection in BALB/c mice was evaluated. RESULTS: Anti-rTspst serum recognized the
      native Tspst protein with 29 kDa in ML crude antigens. Transcription and
      expression of gene was observed at all T. spiralis different developmental stages
      (IIL, adult worms, newborn larvae, and ML). An immunolocalization analysis
      identified Tspst in the cuticle and internal organs of the parasite. An in vitro
      invasion assay showed that, when anti-rTspst serum, serum of mice infected with
      T. spiralis or normal mouse serum were added to the medium, the invasion rate of
      the infective larvae in an IEC monolayer was 25.2%, 11.4%, and 79%, respectively
      (P < 0.05), indicating that anti-rTspst serum partially prevented the larval
      invasion of IECs. After a challenge infection with T. spiralis muscle larvae,
      mice immunized with rTspst conferred a 45.7% reduction in adult worm burden in
      intestines. CONCLUSIONS: In the present study, Tspst was first identified and
      characterized. Tspst is an invasion-related protein of T. spiralis IIL and could
      be considered as a potential vaccine candidate antigen against intestinal T.
      spiralis infection that merits further study.

PMID- 25582128
TI  - Maximum bubble pressure rheology of low molecular mass organogels.
AB  - Maximum bubble pressure rheology is used to characterize organogels of 0.25 wt %
      12-hydroxystearic acid (12-HSA) in mineral oil, 3 wt % (1,3:2,4) dibenzylidene
      sorbitol (DBS) in poly(ethylene glycol), and 1 wt % 1,3:2,4-bis(3,4
      dimethylbenzylidene) sorbitol (DMDBS) in poly(ethylene glycol). The maximum
      pressure required to inflate a bubble at the end of capillary inserted in a gel
      is measured. This pressure is related to the gel modulus in the case of elastic
      cavitation and the gel modulus and toughness in the case of irreversible
      fracture. The 12-HSA/mineral oil gels are used to demonstrate that this is a
      facile technique useful for studying time-dependent gel formation and aging and
      the thermal transition from a gel to a solution. Comparison is made to both
      qualitative gel tilting measurements and quantitative oscillatory shear rheology
      to highlight the utility of this measurement and its complementary nature to
      oscillatory shear rheology. The DBS and DMDBS demonstrate the generality of this
      measurement to measure gel transition temperatures. 

PMID- 25582129
TI  - Structure of bacterial regulatory RNAs determines their performance in
      competition for the chaperone protein Hfq.
AB  - Bacterial regulatory RNAs require the chaperone protein Hfq to enable their
      pairing to mRNAs. Recent data showed that there is a hierarchy among sRNAs in the
      competition for access to Hfq, which could be important for the tuning of sRNA
      dependent translation regulation. Here, seven structurally different sRNAs were
      compared using filter-based competition assays. Moreover, chimeric sRNA
      constructs were designed to identify structure elements important for competition
      performance. The data showed that besides the 3'-terminal oligouridine sequences
      also the 5'-terminal structure elements of sRNAs were essential for their
      competition performance. When the binding of sRNAs to Hfq mutants was compared,
      the data showed the important role of the proximal and rim sites of Hfq for the
      binding of six out of seven sRNAs. However, ChiX sRNA, which was the most
      efficient competitor, bound Hfq in a unique way using the opposite-distal and
      proximal-faces of this ring-shaped protein. The data indicated that the
      simultaneous binding to the opposite faces of Hfq was enabled by separate
      adenosine-rich and uridine-rich sequences in the long, single-stranded region of
      ChiX. Overall, the results suggest that the individual structural composition of
      sRNAs serves to tune their performance to different levels resulting in a
      hierarchy of sRNAs in the competition for access to the Hfq protein. 

PMID- 25582130
TI  - Enantioselective Dissipation of Acephate and Its Metabolite, Methamidophos,
      during Tea Cultivation, Manufacturing, and Infusion.
AB  - The enantioselective dissipation of acephate and its metabolite, methamidophos,
      was investigated during tea cultivation, manufacturing, and infusion, using
      QuEChERS sample preparation technique and gas chromatography coupled with a BGB
      176 chiral column. Results showed that (+)-acephate and (-)-acephate dissipated
      following first-order kinetics in fresh tea leaves with half-lives of 1.8 and 1.9
      days, respectively. Acephate was degraded into a more toxic metabolite,
      methamidophos. Preferential dissipation and translocation of (+)-acephate may
      exist in tea shoots, and (-)-methamidophos was degraded more rapidly than (+)
      methamidophos. During tea manufacturing, drying and spreading (or withering)
      played important roles in the dissipation of acephate enantiomers. The
      enantiometic fractions of acephate changed from 0.495-0.496 to 0.479-0.486 (P <=
      0.0081), whereas those of methamidophos changed from 0.576-0.630 to 0.568-0.645
      (P <= 0.0366 except for green tea manufacturing on day 1), from fresh tea leaves
      to made tea. In addition, high transfer rates (>80%) and significant
      enantioselectivity (P <= 0.0042) of both acephate and its metabolite occurred
      during tea brewing.

PMID- 25582131
TI  - Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR
      HIFU: therapeutic effect in rabbit Vx2 tumours.
AB  - PURPOSE: The aim of this study was to determine whether localised drug release
      using thermosensitive liposomal doxorubicin (TLD) and mild hyperthermia produced
      by a clinical magnetic resonance high intensity focused ultrasound (MR-HIFU)
      system improves anti-tumour efficacy over TLD alone in rabbit Vx2 tumours.
      MATERIALS AND METHODS: Rabbits bearing one Vx2 thigh tumour (n = 6 per group)
      were administered TLD (1.67 mg/kg) either with or without MR-HIFU mild
      hyperthermia (20 min, 42.0  degrees C). Tumour progression was measured using
      contrast-enhanced T1-weighted MR imaging. Toxicity was evaluated by changes in
      body weight, blood counts, and blood chemistry. Tumour volume, body weight, and
      blood data were acquired weekly for the first month and biweekly thereafter.
      RESULTS: Rabbits treated with TLD plus MR-HIFU mild hyperthermia had target
      region temperatures with spatial-median, temporal-mean of 41.4 degrees  +/- 0.6 
      degrees C; 10th and 90th percentile temperatures were 40.2 and 42.7  degrees C.
      All six rabbits that received TLD alone had rapid tumour progression and reached
      the tumour size end point (maximum dimension >6 cm) within 24 days. Four of six
      rabbits treated with TLD plus MR-HIFU mild hyperthermia survived to the study end
      point of 60 days; one reached tumour size end point, one had hyperthermia-related
      toxicity, all had at least a transient decrease in tumour volume. Weekly body
      weight, complete blood counts, and blood chemistry did not reveal additional
      evidence of drug or hyperthermia-related toxicity. CONCLUSIONS: Rabbit Vx2
      tumours treated with a single infusion of TLD during MR-HIFU mild hyperthermia
      had reduced tumour growth vs. tumours treated with TLD alone. These findings are
      an important step toward clinical translation of localised drug delivery using MR
      HIFU and TLD.

PMID- 25582132
TI  - Trapping effect on a small molecular drug with vascular-disrupting agent CA4P in
      rodent H22 hepatic tumor model: in vivo magnetic resonance imaging and postmortem
      inductively coupled plasma atomic emission spectroscopy.
AB  - The aim of the present study is to verify the trapping effect of combretastatin A
      4-phosphate (CA4P) on small molecular drugs in rodent tumors. Mice with H22
      hepatocarcinoma were randomized into groups A and B. Magnetic resonance imaging
      (MRI) of T1WI, T2WI, and DWI was performed as baseline. Mice in group A were
      injected with Gd-DTPA and PBS. Mice in group B were injected with Gd-DTPA and
      CA4P. All mice undergo CE-T1WI at 0 h, 3 h, 6 h, 12 h, and 24 h. Enhancing
      efficacy of the two groups on CE-T1WI was compared with the signal-to-noise ratio
      (SNR) calculated. Concentrations of gadolinium measured by ICP-AES in the tumor
      were compared between groups. On the early CE-T1WI, tumors were equally enhanced
      in both groups. On the delayed CE-T1WI, the enhancing effect of group A was
      weaker than that of group B. The SNR and the concentration of gadolinium within
      the tumor of group A were lower than that of group B at 6 h, 12 h, and 24 h after
      administration. This study indicates that CA4P could improve the retention of Gd
      DTPA in the tumor and MRI allowed dynamically monitoring trapping effects of CA4P
      on local retention of Gd-DTPA as a small molecular drug. 

PMID- 25582133
TI  - New platforms for multi-functional ocular lenses: engineering double-sided
      functionalized nano-coatings.
AB  - A scalable platform to prepare multi-functional ocular lenses is demonstrated.
      Using rapidly dissolving polyvinylpyrrolidone (PVP) as the active stabilizing
      matrix, both sides of ocular lenses were coated using a modified scaled-up
      masking electrohydrodynamic atomization (EHDA) technique (flow rates variable
      between 5 and 10 uL/min, applied voltage 4-11 kV). Each side was coated (using a
      specially designed flip-able well) selectively with a pre-determined morphology
      and model drug substance. PVP nanoparticles (inner side, to be in contact with
      the cornea, mean size <ca.100 nm) were encapsulated with a probe (flourescein
      dye) and PVP nanofibres (outer side, to be exposed to air and eye lid, mean width
      size <ca.200 nm) were encapsulated with chloramphenicol (5 w/w% PVP). Release of
      the probe and anti-microbial activity (using Staphylococcus aureus NCTC 6571)
      were demonstrated based on rapid dissolution and contact of PVP model substance
      matrix. Adapting these findings further for advanced EHDA technologies
      (encapsulation layering, controllable size and deposition and multi-phase media
      deposition options) and intrinsic material properties (functional
      polymers/excipients and advanced controlled release strategies) suggests several
      therapeutic platforms for ocular lenses can be further developed at ambient
      temperature and pressure. These provide multi-functional properties (in
      personalized delivery, nanomedicine and nanosensors) from a single drug delivery
      device. 

PMID- 25582134
TI  - Computed tomography scanogram compared to long leg radiograph for determining
      axial knee alignment.
AB  - BACKGROUND AND PURPOSE: Supine computed tomography scanogram (CTS) is a commonly
      used alternative to weight bearing long leg plain radiograph (LLR) in measuring
      knee alignment. No published studies have validated its use in the native knee
      and the post-unicompartmental replacement knee (UKR). We quantified the
      difference in measurements obtained from CTS and LLR for knee alignment. PATIENTS
      AND METHODS: Supine CT scanograms and weight bearing long leg plain
      anteroposterior radiographs were obtained for 40 knees (in 25 patients), 17 of
      which were native, and 23 of which were post-UKR. The mechanical and anatomical
      axes of the tibio-femoral joint were measured. Bland-Altman plots were used to
      calculate the 1.96 standard deviation limits of agreement between CTS and LLR.
      Intraclass correlation was used to assess intra-rater and inter-rater reliability
      (where values > 0.81 indicate very good reliability). RESULTS: CTS and LLR were
      equally reliable in measurement of the mechanical and anatomical axes of the
      tibio-femoral joint (intraclass correlation coefficient (ICC) > 0.9 for all
      parameters). Statistically significant and clinically relevant differences were
      found between CTS and LLR in measurement of the mechanical axis (limits of
      agreement: UKR -3.2 degrees  to 6.3 degrees ; native -3.2 degrees  to 5.6 degrees
      ) and the anatomical axis (limits of agreement: UKR -3.7 degrees  to 8.7 degrees
      ; native -2.0 degrees  to 8.8 degrees ). INTERPRETATION: Although it is a
      reliable tool, CTS is not necessarily an accurate one for measurement of knee
      alignment when compared to LLR. We recommend that CTS should not be used as a
      substitute for LLR in measurement of the mechanical or anatomical axes of the
      knee.

PMID- 25582135
TI  - Aging and the microbiome: implications for asthma in the elderly?
AB  - In the elderly, asthma remains a clinical challenge. Recognition, diagnosis and
      treatment are all complex. Influenced by processes, such as aging, the
      identification of an 'asthma microbiome' presents a further challenge. This
      editorial discusses aging and the 'asthma microbiome' separately and then
      evaluates their potential relationship. Current evidence suggests that
      differences in the airway microbiome are associated with asthma, however, whether
      such associations are comparable or different for late-onset disease is yet to be
      established. Microbes are now linked to fundamental physiological processes, such
      as aging, based on data from invertebrate systems. This will likely confer
      implications for asthma in the elderly, and it is crucial that such emerging
      scientific data are considered in the context of aging, asthma and late-onset
      disease. 

PMID- 25582136
TI  - Development of learning objectives for neurology in a veterinary curriculum: part
      I: undergraduates.
AB  - BACKGROUND: With an increasing caseload of veterinary neurology patients in first
      opinion practice, there is a requirement to establish relevant learning
      objectives for veterinary neurology encompassing knowledge, skills and attitudes
      for veterinary undergraduate students in Europe. With help of experts in
      veterinary neurology from the European College of Veterinary Neurology (ECVN) and
      the European Society of Veterinary Neurology (ESVN) a survey of veterinary
      neurologic learning objectives using a modified Delphi method was conducted. The
      first phase comprised the development of a draft job description and learning
      objectives by a working group established by the ECVN. In the second phase, a
      quantitative questionnaire (multiple choice, Likert scale and free text) covering
      140 learning objectives and subdivided into 8 categories was sent to 341 ESVN and
      ECVN members and a return rate of 62% (n = 213/341) was achieved. RESULTS: Of
      these 140 learning objectives ECVN Diplomates and ESVN members considered 42
      (30%) objectives as not necessary for standard clinical veterinary neurology
      training, 94 (67%) were graded to be learned at a beginner level and 4 (3%) at an
      advanced level. The following objectives were interpreted as the most important
      day one skills: interpret laboratory tests, perform a neurological examination
      and establish a neuroanatomical localization. In this survey the three most
      important diseases of the central nervous system included epilepsy,
      intervertebral disc disease and inflammatory diseases. The three most important
      diseases of the peripheral nervous system included polyradiculoneuritis,
      myasthenia gravis and toxic neuropathies. CONCLUSIONS: The results of this study
      should help to reform the veterinary curriculum regarding neurology and may
      reduce the phenomenon of "Neurophobia".

PMID- 25582137
TI  - Modern methods for endoscopic treatment of obstructive pulmonary diseases.
AB  - BACKGROUND: Despite modern medicine's greatest efforts, many patients suffering
      from chronic obstructive pulmonary disease (COPD) and asthma remain refractory to
      the best treatments available. Bronchoscopy is increasingly being used to explore
      new approaches for treating these diseases, and several new techniques have
      recently shown encouraging results. The purpose of this review will be to shed
      some light on these methods. METHODS: We searched Pubmed and Embase for English
      language articles from 1995 to September 2014, as well as ongoing trials on
      ClinicalTrials.gov. The following prespecified terms were used to search for
      clinical trials and case reports from the past 20 years: "endoscopic treatment of
      COPD", "endobronchial valve", and "bronchial thermoplasty". RESULTS AND
      DISCUSSION: In search for new COPD treatments, several trials have assessed the
      efficacy of one-way valves and other conceptually similar techniques including
      biological sealants and thermal vapor ablation. These methods all operate within
      a similar paradigm where the intention is to maximize ventilation of the
      remaining healthy parts of the lung, and to minimize the use and the space
      occupied by the diseased lung tissue. Similarly, a new non-pharmacologic
      therapeutic approach in asthma, bronchial thermoplasty (BT), was recently
      approved for use in the United States for adults with severe disease. The goal is
      to reduce the mass of hypertrophied smooth muscle in the bronchi to decrease
      bronchoconstriction. CONCLUSION: Both BT and the bronchoscopic treatments for
      COPD have shown promising results in recent studies, suggesting the onset of a
      new direction in obstructive lung disease treatment.

PMID- 25582138
TI  - Feasibility for developing cardiovascular exercise recommendations for persons
      with motor-complete paraplegia based on manual wheelchair propulsion; A protocol
      and preliminary data.
AB  - BACKGROUND: The Center for Disease Control, American Heart Association, and
      American College of Sports Medicine recommendations for duration and intensity of
      exercise are based on the amount of energy expenditure required to maintain
      cardiovascular health in able body individuals; 1000 Kilocalories (Kcals) per
      week of energy expenditure has been demonstrated to achieve this effect. Manual
      wheelchair propulsion (MWP) represents a practical and accessible form of
      exercise for individuals with paraplegia. OBJECTIVE: To describe a method to
      determine the duration of MWP required to expend 1000 Kcals, when performed by
      individuals with paraplegia due to motor-complete spinal cord injury (SCI). STUDY
      DESIGN: Cross-sectional study. SETTING: Rehabilitation Research Laboratory.
      PARTICIPANTS: Sixteen adults with motor complete T3-T12 paraplegia (body mass
      index < 35, duration of paraplegia > 3 months). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Indirect calorimetry during MWP was measured in order to
      calculate caloric expenditure per minute. These data were used to calculate the
      number of minutes of MWP required to expend 1000 Kcal in one week. RESULTS:
      During MWP, participants expended 3.3 +/- 1.0 Kcal/minute. Based on this figure,
      1000 Kcal of energy expenditure in one week would require 303 minutes of MWP per
      week, or 43.3 minutes per day, 7 days per week. CONCLUSIONS: Our data suggest
      that it is feasible to create a practical and accessible exercise recommendation
      based on manual wheelchair propulsion for individuals with paraplegia due to
      motor-complete SCI. Larger studies are needed in order to develop accurate
      exercise recommendations for persons with SCI.

PMID- 25582139
TI  - Elderly patients with squamous cell carcinoma of the head and neck and the
      benefit of multimodality therapy.
AB  - BACKGROUND: Limited data are available regarding outcomes in elderly head and
      neck cancer patients. This retrospective study was designed to characterize head
      and neck cancer in geriatric patients. PATIENTS AND METHODS: This study included
      all patients in a large university-based tumor registry who were diagnosed with
      head and neck cancer from January 1, 1990, to December 31, 2005. Patients aged
      >=70 years at the time of diagnosis were defined as older. Overall survival and
      progression-free survival were censored at 60 months. Survival differences were
      compared using the log-rank test. Hazard ratios were estimated using a Cox
      proportional hazards model, adjusting for potential confounders. RESULTS: Of
      1,598 patients identified, 1,166 patients were aged <70 years (i.e., younger) and
      281 patients were aged >=70 years (older). When controlling for possible
      confounders, older patients were nearly twice as likely to die within 5 years as
      their younger counterparts (hazard ratio: 1.92). The median life expectancy for
      older patients was nearly 5 years for stage I-II disease and <2 years for stage
      III-IV disease. Older patients with stage III-IV disease who received
      multimodality therapy had 5-year survival similar to that younger patients with
      stage III-IV disease who were treated similarly (33.2% vs. 44.0%). Older patients
      with stage III-IV disease who received single-modality therapy had extremely poor
      survival compared with all other patients (hazard ratio for progression-free
      survival: 1.5). CONCLUSION: This study highlights the need for better
      understanding of the factors affecting head and neck cancer outcomes in elderly
      patients. Information about life expectancy in elderly head and neck cancer
      patients may help guide treatment decisions.

PMID- 25582140
TI  - How well do medical oncologists manage chronic cancer pain? A national survey.
AB  - BACKGROUND: Cancer pain is usually managed by oncologists, occasionally with
      input from specialists in hospice and palliative medicine (PLM) or pain medicine
      (PMD). We evaluated the knowledge of cancer pain management in these three
      specialty groups. METHODS: Eight vignettes depicting challenging scenarios of
      patients with poorly controlled pain were developed; each had five or six
      treatment choices. Respondents indicated choices likely to be safe and
      efficacious as "true" and choices likely to be unsafe or inefficacious as
      "false." Two questionnaires were created, each with four vignettes. Three
      anonymous mailings targeted geographically representative U.S. samples of 570
      oncologists, 266 PMD specialists, and 280 PLM specialists, each randomly assigned
      one version of the questionnaire. Vignette scores were normalized to a 0-100
      numeric rating scale (NRS); a score of 50 indicates that the number of correct
      choices equals the number of incorrect choices (consistent with guessing).
      RESULTS: Overall response rate was 49% (oncologists, 39%; PMD specialists, 48%;
      and PLM specialists, 70%). Average vignette score ranges were 53.2-66.5, 45.6
      65.6, and 50.8-72.0 for oncologists, PMD specialists, and PLM specialists,
      respectively. Oncologists scored lower than PLM specialists on both
      questionnaires and lower than PMD specialists on one. On a 0-10 NRS, oncologists
      rated their ability to manage pain highly (median 7, with an interquartile range
      [IQR] of 5-8). Lower ratings were assigned to pain-related training in medical
      school (median 3, with an IQR of 2-5) and residency/fellowship (median 5, with an
      IQR of 4-7). Oncologists older than 46-47 years rated their training lower than
      younger oncologists. CONCLUSION: These data suggest that oncologists and other
      medical specialists who manage cancer pain have knowledge deficiencies in cancer
      pain management. These gaps help clarify the need for pain management education.

PMID- 25582141
TI  - Prognostic factors of survival in a randomized phase III trial (MPACT) of weekly
      nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with
      metastatic pancreatic cancer.
AB  - BACKGROUND: nab-Paclitaxel in combination with gemcitabine has emerged as a new
      treatment option for patients with metastatic pancreatic cancer (MPC), based on
      superiority over gemcitabine demonstrated in the phase III MPACT trial.
      Previously, Karnofsky performance status (KPS) score and the presence of liver
      metastases were shown to be predictive of survival with nab-paclitaxel plus
      gemcitabine treatment. This analysis sought to further explore the relationship
      between clinical characteristics and survival in the MPACT trial and to identify
      potential predictors of overall survival and progression-free survival in
      patients with MPC. MATERIALS AND METHODS: Cox regression models adjusted for
      stratification factors and a stepwise multivariate analysis of prespecified
      baseline prognostic factors were performed. RESULTS: Treatment effect was
      significantly associated with survival, with a similar magnitude of reduction in
      risk of death compared with the previously reported primary analysis. Treatment
      effect consistently favored nab-paclitaxel plus gemcitabine across the majority
      of the prespecified factors. In addition to KPS score and presence of liver
      metastases, age and number of metastatic sites were independent prognostic
      factors of overall and progression-free survival. Baseline carbohydrate antigen
      19-9 was not found to be an independent prognostic factor of survival in this
      analysis. CONCLUSION: The results of this analysis confirm broad utility of nab
      paclitaxel plus gemcitabine for the treatment of MPC. In addition, these findings
      suggest that KPS score, presence of liver metastases, age, and number of
      metastatic sites are important predictors of survival that may be useful when
      making treatment decisions and designing future clinical trials.

PMID- 25582142
TI  - Bevacizumab in combination with radiotherapy and temozolomide for patients with
      newly diagnosed glioblastoma multiforme.
AB  - BACKGROUND: Patients with a newly diagnosed glioblastoma multiforme (GBM) have a
      high risk of recurrent disease with a dismal outcome despite intensive treatment
      of sequential surgery and chemoradiotherapy with temozolomide (TMZ), followed by
      TMZ as a single agent. Bevacizumab (BV) may increase response rates to
      chemotherapy in the recurrent treatment setting of GBM. We hypothesized that a
      neoadjuvant treatment strategy for patients with newly diagnosed GBM using
      chemoradiotherapy plus BV would improve resectability and thus survival. We
      performed a phase II trial of the treatment strategy of BV plus chemoradiation to
      determine the safety of this combination in patients who had already undergone
      primary surgery for their GBM. METHODS: After a biopsy (6 patients) or a
      resection (13 patients) of a newly diagnosed GBM, 19 patients received
      radiotherapy (30 fractions of 2 Gy) in combination with daily TMZ 75 mg/m(2) and
      BV 10 mg/kg on days 1, 14, and 28, followed by 6 monthly cycles of TMZ 150-200
      mg/m(2) on days 1-5. RESULTS: The overall response rate was 26%. Three patients
      had a complete response after resection, and in two patients, a complete response
      after resection followed by chemoradiation plus BV was seen. No grade 3-4
      toxicities were observed during combination treatment. The median progression
      free survival was 9.6 months (95% confidence interval [CI]: 4.3-14.4 months). The
      median overall survival was 16 months (95% CI: 8.1-26.3 months), similar to a
      matched control group that received standard chemoradiotherapy from our
      institution. CONCLUSION: Combination of bevacizumab with radiotherapy and TMZ is
      safe and feasible in patients with newly diagnosed GBM, but because of low
      response rates, this treatment strategy does not favor a neoadjuvant approach.

PMID- 25582143
TI  - Percutaneous treatment of adult isthmic aortic coarctation: acute and long-term
      clinical and imaging outcome with a self-expandable uncovered nitinol stent.
AB  - BACKGROUND: To present perioperative and long-term results of percutaneous
      treatment of adult isthmic coarctation of the aorta by means of a self-expandable
      closed-web uncovered nitinol stent (Sinus-XL, Optimed, Esslingen, Germany).
      METHODS AND RESULTS: Preoperative, perioperative, and long-term clinical and
      computed tomographic angiography data were collected and analyzed prospectively.
      A total of 52 consecutive patients were treated with the Sinus-XL stent. Mean age
      was 36.6 (21-67) years, peak invasive trans-coarctation of the aorta gradient was
      54.7 +/- 9.9 mm Hg, and upper body hypertension unresponsive to medical treatment
      was present in all patients. Mean stent diameter and length were 24.2 mm (22-28
      mm) and 70.4 mm (40-80 mm), respectively. Eight patients (15.4%) required
      coarctation of the aorta predilatation. All patients underwent poststent
      dilatation with a noncompliant balloon. Postoperative peak gradient (3.3 +/- 2.5
      mm Hg) was reduced significantly (P < 0.001) and minimal aortic diameter was
      increased significantly (4.6 +/- 1.9 versus 18.6 +/- 2.5 mm; P < 0.001). All
      patients were discharged home (mean hospitalization, 3.5 days). At follow-up
      (47.6 months; 12-84), 1 (1.9%) noncardiovascular mortality was reported. Aortic
      computed tomography confirmed the absence of stent collapse and secondary
      migration and documented stability in aortic diameter (18.3 +/- 2.7 mm). Thirty
      patients (57.7%) were completely weaned-off antihypertensive medications and
      their use dropped from 2.6 to 0.9 drugs/patient (P < 0.001). Ankle-brachial
      pressure index increased from 0.75 to 0.98 (P < 0.001). CONCLUSIONS: Adult
      coarctation of the aorta treatment by means of a self-expandable uncovered stent
      is safe and durable. The peculiar stent design maintains adequate localized
      radial strength over time with minimal trauma on the adjacent aortic wall and
      negligible device-related complications. Blood pressure control optimization is
      immediate and persistent even at long-term follow-up.

PMID- 25582145
TI  - Coronary artery revascularization in chronic kidney disease: time for a
      randomized trial.

PMID- 25582144
TI  - Clinical outcomes of treatment by percutaneous coronary intervention versus
      coronary artery bypass graft surgery in patients with chronic kidney disease
      undergoing index revascularization in Ontario.
AB  - BACKGROUND: There is a paucity of data on the comparative effectiveness of
      percutaneous coronary intervention using contemporary drug-eluting stent (DES)
      compared with coronary artery bypass graft (CABG) surgery in patients with
      chronic kidney disease. METHODS AND RESULTS: A population-based study was
      performed using the Cardiac Care Network, a provincial registry of all patients
      undergoing cardiac catheterization in Ontario, to evaluate patients treated with
      either percutaneous coronary intervention using DES or CABG between October 1,
      2008, and September 30, 2011. Chronic kidney disease was defined as creatinine
      clearance <60 mL/min. A total of 1786 propensity-matched patients from 4006
      patients with chronic kidney disease undergoing index revascularization for
      multivessel disease with either DES or isolated CABG (n=893 each group) were
      analyzed. Baseline and procedural characteristics between percutaneous coronary
      intervention and CABG groups were well-balanced, including urgent
      revascularization priority, diabetes mellitus, left ventricular function, and 3
      vessel disease. The 1-, 2-, and 3-year Kaplan-Meier survival analyses in
      propensity-matched patients favored CABG (93.2% versus 89.3%; 86.6% versus 80.3%;
      80.8% versus 71.5%, respectively; P<0.001). The CABG cohort had greater 1-, 2-,
      and 3-year freedom from major adverse cardiac and cerebrovascular events (89.4%
      versus 71.2%; 81.9% versus 60.5%; 75.2% versus 51.8%, respectively; P<0.001). Cox
      regression analysis identified DES use to be associated with greater hazard for
      late mortality (hazard ratio, 1.58; 95% confidence interval, 1.32-1.90) and major
      adverse cardiac and cerebrovascular events (2.62; 2.28-3.01; all P<0.001).
      CONCLUSIONS: In this large provincial registry, CABG was associated with improved
      early and late clinical outcomes when compared with percutaneous coronary
      intervention using DES in patients with chronic kidney disease undergoing index
      revascularization.

PMID- 25582146
TI  - Caveat emptor: self-expanding stents in the management of arch coarctation in the
      adult.

PMID- 25582147
TI  - Laboratory identification of donor-derived coxsackievirus b3 transmission.
AB  - Unexpected donor-to-recipient infectious disease transmission is an important,
      albeit rare, complication of solid organ transplantation. Greater work and
      understanding about the epidemiology of these donor-derived transmissions is
      continually required to further mitigate this risk. Herein we present the first
      reported case of proven donor-derived transmission of coxsackievirus serogroup-3,
      an enterovirus, following solid organ transplant. Swift and effective
      communication between the organ donation agency, treating physicians, laboratory
      testing and notification ensured a coordinated approach. The resulting clinical
      syndromes in the organ recipients were mild. This case highlights the requirement
      for ongoing surveillance over a broad range of infecting pathogens that may
      present as a donor-derived infection. 

PMID- 25582148
TI  - A regulatory boost for oral health in nursing homes.

PMID- 25582149
TI  - Predatory publishing practices and nurses.

PMID- 25582150
TI  - Re: guest editorial by Berno van Meijel, Vol. 50, No. 1, January 2014.

PMID- 25582151
TI  - Language ability, executive functioning and behaviour in school-age children.
AB  - BACKGROUND: Many children with language impairment present with deficits in other
      areas, including executive functioning (EF), attention and behaviour. Similarly,
      many children receiving services for attention or behaviour problems have
      deficits in language ability. AIMS: To evaluate the relations among EF, language
      ability and behaviour problems in a sample of school-age children with a wide
      range of language and behaviour profiles. The following research questions were
      addressed: Does performance on EF tasks predict language ability? Do language
      ability and EF predict problems with attention, internalizing and/or
      externalizing? METHODS & PROCEDURES: EF was defined as referring to the
      separable, yet related, processes of shifting, updating working memory and
      inhibition as specified in the latent variable model of EF. Children aged 8-11
      years recruited from an urban school district completed standardized language and
      cognitive assessments and a computerized task assessing EF. Their parents
      completed standardized questionnaires assessing the children's EF and problem
      behaviours. Regression analyses were conducted. OUTCOMES & RESULTS: Regression
      analyses revealed that EF did not contribute to language ability beyond the
      variance accounted for by nonverbal reasoning. Language ability contributed to
      attention problems when entered as a single predictor, but was no longer
      significant when the EF measures were added to the model. Language ability did
      not significantly contribute to internalizing or externalizing behaviour
      problems. Parent-reported inhibition was a robust predictor of attention,
      internalizing and externalizing behaviour problems. CONCLUSIONS & IMPLICATIONS:
      In this sample of school-age children, language ability was related to attention
      problems, but not to internalizing or externalizing. Children with behaviour
      problems may have particular difficulty with inhibition.

PMID- 25582152
TI  - Comparison of the in-feed glucose test and the oral sugar test.
AB  - REASONS FOR PERFORMING STUDY: The in-feed oral glucose test (OGT) and oral sugar
      test (OST) are advocated as field tests of insulin sensitivity in horses and
      ponies but have not been directly compared. OBJECTIVES: To compare the insulin
      response to OGT and OST in 8 ponies and 5 horses of unknown insulin sensitivity.
      STUDY DESIGN: Experimental, randomised crossover study. METHODS: Animals were
      fasted for 8 h overnight before and throughout testing. They were fed 1 g/kg bwt
      glucose powder with chaff (OGT) or 0.15 ml/kg bwt corn syrup (KaroTM Light Syrup;
      OST) was administered per os in a randomised crossover study with 48 h between
      tests. Blood samples were obtained at 0, 30, 60, 75, 90, 120 and 180 min. The
      maximal insulin concentration (Cmaxi ), time to maximal insulin concentration
      (Tmaxi ) and area under the curve of insulin concentration over time (AUCi ) for
      the tests were compared using Student's paired t test. The effect of individual
      subject, horse or pony and test were analysed using a linear mixed model.
      RESULTS: The OGT Cmaxi (mean +/- s.d.; 154 +/- 116 MUiu/ml), Tmaxi (136 +/- 52
      min) and AUCi (15,308 +/- 9886 MUiu/ml/min) were significantly (P<0.05) greater
      compared with the OST Cmaxi (72 +/- 55 MUiu/ml), Tmaxi (63 +/- 25 min) and AUCi
      (5980 +/- 4151 MUiu/ml/min). The Cmaxi , Tmaxi and AUCi varied significantly
      between individual subjects. The Tmaxi was significantly different between horses
      and ponies during OGT and OST. Using previously defined criteria of insulin
      dysregulation, OGT identified 7/13 animals as insulin resistant, whereas OST
      identified 5/13 animals as insulin resistant. CONCLUSIONS: The OGT and OST showed
      agreement in identification of insulin dysregulation in 85% of equine subjects.
      Results of the OGT and OST are not comparable in all cases. Further work is
      required to establish which test more accurately diagnoses insulin dysregulation
      in horses and ponies.

PMID- 25582153
TI  - Influence of different drugs on HIV risk in people who inject: systematic review
      and meta-analysis.
AB  - AIMS: To assess systematically the risk of HIV acquisition by type of drug
      injected across different settings. METHODS: A systematic review and meta
      analysis were conducted. Databases were searched for studies of HIV incidence in
      people who inject different drugs (PWID). Pooled HIV incidence rate ratio (IRR)
      was used to compare HIV risk between injecting and not-injecting a given drug,
      when possible, or otherwise with those reported not to have injected the
      substance. Pooled estimates of crude IRR were derived using random-effects
      models. Variations in IRR were assessed in subgroup analyses, by drug and
      geographical region. RESULTS: Of 5779 studies screened, 15 were included. HIV
      incidence was reported for people injecting cocaine (eight: North America,
      Europe), amphetamine-type stimulants (ATS) (four: Western and Eastern Europe,
      Asia), heroin (11: all settings), opiate-stimulants (four: North America, Western
      and Eastern Europe) and opiates-sedatives (five: Europe, Asia). HIV risk in
      cocaine injectors was 3.6 times 95% confidence interval (CI) = 2.8-4.7, I(2)  =
      0%; n = 4) that of non-injectors and 3.0 for ATS injectors (95% CI = 2.2-4.1,
      I(2)  = 0%; n = 2). Higher sexual risk was reported in cohorts injecting
      stimulants. Compared to not-injecting, HIV IRR was 2.8 (95% CI = 1.7-4.7, I(2)  =
      77%; n=6) for all heroin injectors and 3.5 (95% CI = 2.3-5.2, I(2)  = 40%; n=5)
      for heroin injectors in Asia and Europe. CONCLUSION: The risk of HIV acquisition
      in people who inject drugs appears to vary by drug type but differences are not
      statistically significant, precluding conclusive grading of risk.

PMID- 25582154
TI  - Influence of birthweight on perinatal outcome in fetuses with antenatal diagnosis
      of congenital heart disease.
AB  - AIM: The incidence of congenital heart disease (CHD) accounts for the largest
      proportion of infant mortality attributable to birth defects. Associations have
      previously been reported between CHD and low birthweight. Low birthweight is
      independently associated with adverse outcome and has characteristically been
      calculated using population-based charts. This aim of this study was to determine
      the incidence of small for gestational age (SGA) in fetuses with CHD utilizing
      customized birthweight centiles and to determine the effect of SGA on adverse
      outcome. METHODS: A retrospective cohort study was performed between 2006 and
      2011. All singleton fetuses with CHD, with no associated karyotype or structural
      extra-cardiac abnormalities, who delivered at St Thomas's Hospital, London, were
      included. Population and customized birthweight centiles were calculated and
      perinatal outcome data were recorded. RESULTS: A total of 17% of fetuses with CHD
      had a birthweight centile <10th when population centiles were used, and 25% when
      customized birthweight centiles were applied. There was no correlation between
      SGA and increased adverse perinatal outcome. CONCLUSIONS: A high proportion of
      fetuses with CHD are classified as SGA when both population and customized
      birthweight centiles are used. SGA does not correlate with adverse outcome in the
      perinatal period. The cardiac defect therefore appears to be the main determinant
      of outcome and not the size of the baby at delivery.

PMID- 25582155
TI  - Moving toward clarity in the treatment of allergic rhinitis.

PMID- 25582156
TI  - The history and progression of treatments for allergic rhinitis.
AB  - This article intends to place new treatments in the context of allergic rhinitis
      (AR) treatment history. The medical literature was searched for significant
      advances and changes in AR treatment. Historical data on AR treatment options and
      management were selected. Reviews of AR management published throughout the 20th
      century were included to provide context for treatment advances. Modern AR
      treatment began in the early 20th century with immunotherapy and was soon
      followed by the emergence of antihistamine therapy in the 1930s. Numerous
      treatments for AR have been used over the ensuing decades, including
      decongestants, mast cell stabilizers, and leukotriene receptor antagonists.
      Topical corticosteroid options were developed the 1950s, and, added to baseline
      antihistamine therapy, became the foundation of AR treatment. Treatment options
      were significantly impacted after the 1987 Montreal Protocol, which phased out
      the use of chlorofluorocarbon propellant aerosols because of environmental
      concerns. From the mid-1990s until recently, this left only aqueous solution
      options for intranasal corticosteroids (INSs). The approval of the first
      hydrofluoroalkane propellant aerosol INSs for AR in 2012 restored a "dry" aerosol
      treatment option. The first combination intranasal antihistamine/INSs was also
      approved in 2012, providing a novel treatment option for AR. Treatment of AR has
      progressed with new therapeutic options now available. This should continue to
      move forward with agents to alter the allergic mechanism itself and impact the
      disease burden that has a significant impact on patient outcomes. 

PMID- 25582157
TI  - New intranasal formulations for the treatment of allergic rhinitis.
AB  - Intranasal corticosteroids (INSs) have been effectively used for >40 years for
      the treatment of seasonal allergic rhinitis (SAR) and perennial AR (PAR).
      Following the Montreal Protocol, the initial aerosol formulations using
      chlorofluorocarbon (CFC) propellants were phased out. For the past 20 years,
      aqueous solutions have been the only available option for INS treatment. In 2012,
      the U.S. Food and Drug Administration approved two new nonaqueous aerosol AR
      treatments that use a hydrofluoroalkane (HFA) propellant. In 2012, the first
      intranasal aqueous combination product was also approved. This article reviews
      the clinical profiles of HFA beclomethasone dipropionate (BDP) and HFA
      ciclesonide (CIC) and the aqueous combination intranasal antihistamine (INA)/INS
      formulation of azelastine hydrochloride/fluticasone propionate (AZE/FP). The
      medical literature was searched for clinical trials investigating the use of BDP,
      CIC, and AZE/FP in SAR and PAR. Clinical trials involving aqueous solutions and
      CFC propellant or HFA propellant delivery were included. Data from prescribing
      information and published efficacy and safety data were presented as part of the
      clinical profile for the reviewed agents. AZE/FP has shown efficacy and safety
      comparable or greater with the current AR treatment options. Although efficacy
      comparisons of new HFA formulations have not been investigated in head-to-head
      clinical trials with aqueous formulations, HFA formulations have shown similar
      efficacy rates. Furthermore, HFA formulations may have some additional benefits,
      including a preferable sensory profile for some patients. These new formulations
      will provide additional options for clinicians and patients to better
      individualize therapy for control of AR. 

PMID- 25582159
TI  - A tribute to Professor Kenneth Ian Welsh 17 August 1944-12 August 2014
      [corrected].

PMID- 25582158
TI  - Recommendations for the pharmacologic management of allergic rhinitis.
AB  - Allergic rhinitis (AR) affects at least 60 million people in the United States
      each year, resulting in a major impact on patient quality of life, productivity,
      and direct and indirect costs. As new therapies, data, and literature emerge in
      the management of AR, there is a need to communicate and disseminate important
      information to health care professionals to advance the practice of medicine and
      lessen the disease burden from AR. Treatment recommendations for AR have not been
      updated since the 2012 Food and Drug Administration approval of nonaqueous
      intranasal aerosol agents using hydrofluoroalkane propellants and the first
      aqueous intranasal combination product. Here, we present an updated algorithm for
      the pharmacologic treatment of AR that includes these new treatment options.
      Treatment recommendations are categorized by disease severity (mild versus
      moderate/severe) and duration of symptoms (episodic versus nonepisodic, with
      episodic defined as <3 days/wk or for <3 weeks). Preferred treatments are
      suggested, as well as alternative options for consideration by clinicians in the
      context of individual patient needs. This recommendation article also outlines
      the importance of treatment monitoring, which can be conducted using the recently
      developed Rhinitis Control Assessment Test. Successful therapeutic outcomes
      depend on multiple factors, including use of the most effective pharmacologic
      agents as well as patient adherence to therapy. Therefore, it is imperative that
      rhinitis patients not only receive the most effective therapeutic options, but
      that they also understand and are able to adhere to the comprehensive treatment
      regimen. Successful treatment, with all of these considerations in mind, results
      in better disease outcomes, improved quality of life for patients, and greater
      economic productivity in the home and workplace. 

PMID- 25582160
TI  - Laryngopyocele: a rare neck mass and an uncommon excision.

PMID- 25582161
TI  - HLA-B*46:60, a novel variant of HLA-B*46:01:01, detected in a Taiwanese unrelated
      hematopoietic stem cell donor by sequence-based typing.
AB  - One nucleotide replacement at residue 89 of HLA-B*46:01:01 results in a novel
      allele, HLA-B*46:60. 

PMID- 25582162
TI  - Influence of prostate stem cell antigen gene polymorphisms on susceptibility to
      Helicobacter pylori-associated diseases: a case-control study.
AB  - BACKGROUND: Patients with duodenal ulcer have a reduced risk of developing
      gastric cancer compared to those without. Recently, the prostate stem cell
      antigen (PSCA) rs2294008 C>T polymorphism was found to be associated with
      different pathogenesis of duodenal ulcer and gastric cancer developments.
      However, whether PSCA rs2294008 C>T polymorphism is associated with severity of
      gastric mucosal atrophy is unclear. We examined the influence of the PSCA
      rs2294008 C>T polymorphism on susceptibility to H. pylori-related diseases and
      the relationships between PSCA polymorphism and gastric mucosal atrophy. METHODS:
      PSCA rs2294008 C>T polymorphism was assessed in H. pylori-positive Japanese
      patients (n = 488) with noncardia gastric cancer (n = 193), gastric ulcer (n =
      84), duodenal ulcer (n = 61), and atrophic gastritis (n = 150), as well as in H.
      pylori-negatives (n = 266). RESULTS: Frequency of PSCA rs2294008 C/C genotype in
      duodenal ulcer was 36.1%, which was significantly higher than those with gastric
      cancer (12.4%), gastric ulcer (19.0%), gastritis (10.7%), and H. pylori-negatives
      (19.5%) (p < .001). Compared with duodenal ulcer, having the T allele
      significantly increased the risk of gastric cancer (OR: 3.97, 95% CI: 2.02-7.80;
      p < .001), gastric ulcer (2.40, 1.13-5.10; p = .023), and gastritis (4.72, 2.26
      9.86; p < .001). Mean pepsinogen (PG) I/PG II ratio in T allele carriers (2.17 +/
      0.75) was significantly lower than that in C/C genotype (3.39 +/- 1.27, p <
      .001). CONCLUSIONS: The PSCA rs2294008 C>T polymorphism is associated with
      differing susceptibilities to H. pylori-associated diseases. The PSCA rs2294008
      C>T polymorphism may be acting through induction of gastric mucosal atrophy,
      finally leading to development of gastric ulcer and gastric cancer in PSCA
      rs2294008 T allele carriers, but not duodenal ulcer.

PMID- 25582163
TI  - Associations between fitness and mobility capacity in school-aged children with
      cerebral palsy: a longitudinal analysis.
AB  - AIM: The aim of this study was to determine the longitudinal associations among
      fitness components and between fitness and mobility capacity in children with
      cerebral palsy (CP). METHOD: Forty-six children (26 males, 20 females; mean age
      9y 7mo [SD 1y 8mo]) with a bilateral (n=24) or a unilateral spastic CP (n=22)
      participated in aerobic and anaerobic fitness measurements on a cycle ergometer
      and isometric muscle strength tests (Gross Motor Function Classification System
      [GMFCS] level I [n=26], level II [n=12], level III [n=8]). Mobility capacity was
      assessed with the gross motor function measure (GMFM) and a walking capacity
      test. Associations over longitudinal measurements (three or four measurements
      over 1y) were determined since longitudinal data allow a more accurate
      estimation. The associations were determined using a mixed model with fixed
      effects (mobility capacity as dependent variables and fitness components as
      independent variables) and a random intercept. RESULTS: In children with
      bilateral CP, changes in aerobic fitness were associated with changes in
      anaerobic fitness (p<0.001), and changes in aerobic fitness showed an association
      with changes in muscle strength (p<0.05). Anaerobic fitness was not associated
      with muscle strength. No associations between fitness components were found in
      unilateral CP. Anaerobic fitness and muscle strength were significant
      determinants for GMFM and walking capacity in bilateral but not in unilateral CP.
      INTERPRETATION: The longitudinal associations between aerobic and anaerobic
      fitness and mobility indicate that increasing either aerobic or anaerobic fitness
      is associated with improvements in mobility in children with bilateral CP. While
      increasing anaerobic fitness might be beneficial for mobility capacity in
      children with bilateral CP, this is less likely for children with unilateral CP.

PMID- 25582164
TI  - Who does it first? The uptake of medical innovations in the performance of
      thrombolysis on ischemic stroke patients in Germany: a study based on hospital
      quality data.
AB  - BACKGROUND: Since 2000, systemic thrombolysis has been the only approved curative
      and causal treatment for acute ischemic stroke. In 2009, the guidelines of the
      German Society for Neurology were updated and the therapeutic window for
      performing thrombolysis was extended. The implementation of new therapies is
      influenced by many factors. We analyzed the factors at the organizational level
      that influence the implementation of thrombolysis in stroke patients. METHODS:
      The data published by the majority of German hospitals in their structured
      quality reports was assessed. We calculated a regression model in order to
      measure the influence of hospital/department-level characteristics (e.g.,
      teaching status, ownership, location, and number of hospital beds) on the
      implementation of thrombolysis in 2006 (this is the earliest point in time that
      can be analyzed on this data basis). In order to measure the effect of the
      guideline update in 2009 on the thrombolysis rate (TR) change between 2008 and
      2010, we performed a Wilcoxon signed-rank test and utilized a regression model.
      RESULTS: In 2006, 61.5% of a total of 286 neurology departments performed
      systemic thrombolysis to treat ischemic strokes. The influencing factors for the
      use of systemic thrombolysis in 2006 were the existence of a stroke unit (+) and
      a hospital size of between 500 and 1,000 beds (-). A significant increase of the
      mean departmental TR (thrombolysis rate) from 6.7% to 9.2% between 2008 and 2010
      was observed after the guideline update in 2009. For the departments performing
      thrombolysis in 2008 and 2010, our analysis could not show any additional
      influencing factors on a structural level that would explain the TR rise during
      the period 2008-2010. CONCLUSIONS: Because ischemic stroke patients benefit from
      systemic thrombolysis, it is necessary to examine possible barriers at the
      organizational level that hinder the implementation. Our data shows that,
      organizational factors have an influence on the implementation of thrombolysis.
      However, the recent guideline update resulted in a TR rise that occurred at all
      hospitals, regardless of the measured structural conditions, as our analysis
      could not identify any structural factors that might have influenced the TR after
      the guideline update.

PMID- 25582165
TI  - Efficient and facile synthesis of acrylamide libraries for protein-guided
      tethering.
AB  - A kinetic template-guided tethering (KTGT) strategy has been developed for the
      site-directed discovery of fragments that bind to defined protein surfaces, where
      acrylamide-modified fragments can be irreversibly captured in a protein-templated
      conjugate addition reaction. Herein, an efficient and facile method is reported
      for the preparation of acrylamide libraries from a diverse range of amine
      fragments using a solid-supported quaternary amine base. 

PMID- 25582166
TI  - Tunable electrophoretic separations using a scalable, fabric-based platform.
AB  - There is a rising need for low-cost and scalable platforms for sensitive medical
      diagnostic testing. Fabric weaving is a mature, scalable manufacturing technology
      and can be used as a platform to manufacture microfluidic diagnostic tests with
      controlled, tunable flow. Given its scalability, low manufacturing cost (<$0.25
      per device), and potential for patterning multiplexed channel geometries, fabric
      is a viable platform for the development of analytical devices. In this paper, we
      describe a fabric-based electrophoretic platform for protein separation.
      Appropriate yarns were selected for each region of the device and weaved into
      straight channel electrophoretic chips in a single step. A wide dynamic range of
      analyte molecules ranging from small molecule dyes (<1 kDa) to macromolecule
      proteins (67-150 kDa) were separated in the device. Individual yarns behave as a
      chromatographic medium for electrophoresis. We therefore explored the effect of
      yarn and fabric parameters on separation resolution. Separation speed and
      resolution were enhanced by increasing the number of yarns per unit area of
      fabric and decreasing yarn hydrophilicity. However, for protein analytes that
      often require hydrophilic, passivated surfaces, these effects need to be properly
      tuned to achieve well-resolved separations. A fabric device tuned for protein
      separations was built and demonstrated. As an analytical output parameter for
      this device, the electrophoretic mobility of a sedimentation marker, Naphthol
      Blue Black bovine albumin in glycine-NaOH buffer, pH 8.58 was estimated and found
      to be -2.7 * 10(-8) m(2) V(-1) s(-1). The ability to tune separation may be used
      to predefine regions in the fabric for successive preconcentrations and
      separations. The device may then be applied for the multiplexed detection of low
      abundance proteins from complex biological samples such as serum and cell lysate.

PMID- 25582167
TI  - Protective immunity induced by peptides of AMA1, RON2 and RON4 containing T-and B
      cell epitopes via an intranasal route against toxoplasmosis in mice.
AB  - BACKGROUND: Toxoplasma gondii is a ubiquitous protozoan intracellular parasite,
      the causative agent of toxoplasmosis, and a worldwide zoonosis. Apical membrane
      antigen-1 (AMA1) and rhoptry neck protein (RON2, RON4) are involved in the
      invasion of T. gondii. METHODS: This study chemically synthesized peptides of
      TgAMA1, TgRON2 and TgRON4 that contained the T- and B-cell epitopes predicted by
      bioinformatics analysis. We evaluated the systemic response by proliferation,
      cytokine and antibody measurements as well as the mucosal response by examining
      the levels of antigen-specific secretory IgA (SIgA) in the nasal, vesical and
      intestinal washes obtained from mice after nasal immunization with single (AMA1,
      RON2, RON4) or mixtures of peptides (A1 + R2, A1 + R4, R2 + R4, A1 + R2 + R4). We
      also assessed the parasite burdens in the liver and brain as well as the survival
      of mice challenged with a virulent strain. RESULTS: The results showed that the
      mice immunized with single or mixed peptides produced effective mucosal and
      systemic immune responses with a high level of specific antibody responses, a
      strong lymphoproliferative response and significant levels of gamma interferon
      (IFN-gamma), interleukin-2 (IL-2) and IL-4 production. These mice also elicited
      partial protection against acute and chronic T. gondii infection. Moreover, our
      study indicated that mixtures of peptides, especially the A1 + R2 mixture, were
      more powerful and efficient than any other single peptides. CONCLUSIONS: These
      results demonstrated that intranasal immunisation with peptides of AMA1, RON2 and
      RON4 containing T- and B-cell epitopes can partly protect mice against
      toxoplasmosis, and a combination of peptides as a mucosal vaccine strategy is
      essential for future Toxoplasma vaccine development.

PMID- 25582170
TI  - Gene and cell therapy for pancreatic cancer.
AB  - INTRODUCTION: The clinical outcomes of patients with pancreatic cancer are poor,
      and the limited success of classical chemotherapy underscores the need for new,
      targeted approaches for this disease. The delivery of genetic material to cells
      allows for a variety of therapeutic concepts. Engineered agents based on
      synthetic biology are under clinical investigation in various cancers, including
      pancreatic cancer. AREAS COVERED: This review focuses on Phase I - III clinical
      trials of gene and cell therapy for pancreatic cancer and on future implications
      of recent translational research. Trials available in the US National Library of
      Medicine (www.clinicaltrials.gov) until February 2014 were reviewed and relevant
      published results of preclinical and clinical studies were retrieved from
      www.pubmed.gov . EXPERT OPINION: In pancreatic cancer, gene and cell therapies
      are feasible and may have synergistic antitumor activity with standard treatment
      and/or immunotherapy. Challenges are related to application safety, manufacturing
      costs, and a new spectrum of adverse events. Further studies are needed to
      evaluate available agents in carefully designed protocols and combination
      regimens. Enabling personalized cancer therapy, insights from molecular
      diagnostic technologies will guide the development and selection of new gene
      based drugs. The evolving preclinical and clinical data on gene-based therapies
      can lay the foundation for future avenues improving patient care in pancreatic
      cancer.

PMID- 25582168
TI  - Effect modification by vitamin D receptor genetic polymorphisms in the
      association between cumulative lead exposure and pulse pressure: a longitudinal
      study.
AB  - BACKGROUND: Although the association between lead and cardiovascular disease is
      well established, potential mechanisms are still poorly understood. Calcium
      metabolism plays a role in lead toxicity and thus, vitamin D receptor (VDR)
      polymorphisms have been suggested to modulate the association between lead and
      health outcomes. We investigated effect modification by VDR genetic polymorphisms
      in the association between cumulative lead exposure and pulse pressure, a marker
      of arterial stiffness. METHODS: We examined 727 participants (3,100 observations
      from follow-ups from 1991 to 2011) from the Normative Aging Study (NAS), a
      longitudinal study of aging. Tibia and patella bone lead levels were measured
      using K-x-ray fluorescence. Four single nucleotide polymorphisms (SNPs) in the
      VDR gene, Bsm1, Taq1, Apa1, and Fok1, were genotyped. Linear mixed effects models
      with random intercepts were implemented to take into account repeated
      measurements. RESULTS: Adjusting for potential confounders, pulse pressure was
      2.5 mmHg (95% CI: 0.4-4.7) and 1.9 mmHg (95% CI: 0.1-3.8) greater per
      interquartile range (IQR) increase in tibia lead (15 MUg/g) and patella lead (20
      MUg/g), respectively, in those with at least one minor frequency allele in Bsm1
      compared with those with major frequency allele homozygotes. The observed
      interaction effect between bone lead and the Bsm1 genotype persists over time
      during the follow-up. Similar results were observed in effect modification by
      Taq1. CONCLUSIONS: This study suggests that subjects with the minor frequency
      alleles of VDR Bsm1 or Taq1 may be more susceptible to cumulative lead exposure
      related elevated pulse pressure.

PMID- 25582169
TI  - Physico-chemical characterization and pharmacological evaluation of sulfated
      polysaccharides from three species of Mediterranean brown algae of the genus
      Cystoseira.
AB  - BACKGROUND: Seaweed polysaccharides are highly active natural substances having
      valuable applications. The present study was conducted to characterize the
      physico-chemical properties of sulphated polysaccharides from three Mediterranean
      brown seaweeds (Cystoseira sedoides, Cystoseira compressa and Cystoseira crinita)
      and to evaluate their anti-radical, anti-inflammatory and gastroprotective
      activities. METHODS: The different rates of neutral sugars, uronic acids, L
      fucose and sulphate content were determined by colorimetric techniques. The
      different macromolecular characteristics of isolated fucoidans were identified by
      size exclusion chromatography equipped with a triple detection: multiangle light
      scattering, viscometer and differential refractive index detectors,
      (SEC/MALS/VD/DRI). Anti-inflammatory activity was evaluated, using the
      carrageenan-induced rat paw edema test in comparison to the references drugs
      Acetylsalicylate of Lysine and Diclofenac. The gastroprotective activity was
      determined using HCl/EtOH induced gastric ulcers in rats and to examine the
      antioxidant effect of fucoidans in the three species, the free radical scavenging
      activity was determined using 1,1-diphenyl-2-picrylhydrazyl. RESULTS: The
      pharmacological evaluation of the isolated fucoidans for their anti-inflammatory,
      and their gastroprotective effect established that these products from C.
      sedoides, C. compressa and C. crinita exhibited a significant anti-inflammatory
      activity at a dose of 50 mg/kg, i.p; the percentages of inhibition of the oedema
      were 51%, 57% and 58% respectively. And, at the same dose, these fucoidans from
      C. sedoides and C. compressa showed a significant decrease of the intensity of
      gastric mucosal damages compared to a control group by 68%, whereas, the fucoidan
      from C. crinita produced a less gastroprotective effect. Furthermore, the
      isolated fucoidans exhibited a radical scavenging activity. CONCLUSION: The
      comparative study of fucoidans isolated from three species of the genus
      Cystoseira showed that they have similar chemicals properties and relatives anti
      radical, anti-inflammatory and gastroprotective activities which are found to be
      promising.

PMID- 25582172
TI  - Sorghum extract exerts cholesterol-lowering effects through the regulation of
      hepatic cholesterol metabolism in hypercholesterolemic mice.
AB  - The purpose of this study is to investigate that sorghum extract (SE) exerts
      cholesterol-lowering effects through the regulation of hepatic cholesterol
      metabolism-related protein expression. C57BL/6 mice were fed a modified AIN-93G
      diet (NC) with saline, or a modified AIN-93G diet with 2% cholesterol and 0.25%
      cholic acid with either saline (HC) or 600 mg SE/kg body weight (HC-SE). Levels
      of total cholesterol and triglycerides in serum and liver were significantly
      lower in HC-SE than in HC. The expression of 3-hydroxy-3-methylglutaryl coenzyme
      A reductase, sterol regulatory elementary binding protein2 and fatty acid
      synthase were significantly lower, whereas phosphorylated AMP-activated protein
      kinase expression was significantly higher in HC-SE than in HC. Cholesterol 7
      alpha hydroxylase expression was also significantly higher in mice given SE than
      in those given HC. These results suggest that the cholesterol-lowering effect of
      SE may be related to the regulation of hepatic cholesterol metabolism in this
      mouse model.

PMID- 25582171
TI  - Reconstruction and analysis of a genome-scale metabolic model of the oleaginous
      fungus Mortierella alpina.
AB  - BACKGROUND: Mortierella alpina is an oleaginous fungus used in the industrial
      scale production of arachidonic acid (ARA). In order to investigate the metabolic
      characteristics at a systems level and to explore potential strategies for
      enhanced lipid production, a genome-scale metabolic model of M. alpina was
      reconstructed. RESULTS: This model included 1106 genes, 1854 reactions and 1732
      metabolites. On minimal growth medium, 86 genes were identified as essential,
      whereas 49 essential genes were identified on yeast extract medium. A series of
      sequential desaturase and elongase catalysed steps are involved in the synthesis
      of polyunsaturated fatty acids (PUFAs) from acetyl-CoA precursors, with
      concomitant NADPH consumption, and these steps were investigated in this study.
      Oxygen is known to affect the degree of unsaturation of PUFAs, and robustness
      analysis determined that an oxygen uptake rate of 2.0 mmol gDW(-1) h(-1) was
      optimal for ARA accumulation. The flux of 53 reactions involving NADPH was
      significantly altered at different ARA levels. Of these, malic enzyme (ME) was
      confirmed as a key component in ARA production and NADPH generation. When using
      minimization of metabolic adjustment, a knock-out of ME led to a 38.28% decrease
      in ARA production. CONCLUSIONS: The simulation results confirmed the model as a
      useful tool for future research on the metabolism of PUFAs.

PMID- 25582174
TI  - Relationship between chewing behavior and body weight status in fully dentate
      healthy adults.
AB  - Recent research indicates that chewing behavior may influence energy intake and
      energy expenditure. However, little is known about the relationship between
      chewing behavior and body weight status. In the present study, 64 fully dentate
      normal-weight or overweight/obese adults were asked to consume five portions of a
      test food and the number of chewing cycles, chewing duration before swallowing
      and chewing rate were measured. Adjusting for age and gender, normal-weight
      participants used a higher number of chewing cycles (p = 0.003) and a longer
      chewing duration (p < 0.001) to consume each portion of the food, compared to
      overweight/obese participants. However, there was no significant difference in
      their chewing rate (p = 0.597). A statistically significant negative correlation
      between body mass index and the number of chewing cycles (r = -0.296, p = 0.020)
      and chewing duration (r = -0.354, p = 0.005) was observed. In conclusion, these
      results suggest that chewing behavior is associated with body weight status in
      fully dentate healthy adults.

PMID- 25582173
TI  - Turmeric and black pepper spices decrease lipid peroxidation in meat patties
      during cooking.
AB  - Spices are rich in natural antioxidants and have been shown to be potent
      inhibitors of lipid peroxidation during cooking of meat. Turmeric contains unique
      conjugated curcuminoids with strong antioxidant activity. Piperine, one of the
      main constituents of black pepper, is known to increase the bioavailability of
      curcuminoids in mouse and human studies when consumed with turmeric. We
      investigated whether adding black pepper to turmeric powder may further inhibit
      lipid peroxidation when added to meat patties prior to cooking. The addition of
      black pepper to turmeric significantly decreased the lipid peroxidation in
      hamburger meat. When investigating the antioxidant activity of the main chemical
      markers, we determined that piperine did not exhibit any antioxidant activity.
      Therefore, we conclude that other black pepper ingredients are responsible for
      the increased antioxidant activity of combining black pepper with turmeric
      powder. 

PMID- 25582175
TI  - Stakeholders' perception of the nutrition and health claim regulation.
AB  - In 2007, the Nutrition and Health Claim Regulation (NHCR) entered into force,
      which required scientific substantiation of health claims. In the field of
      antioxidants, most proposed claims were negatively assessed by the European Food
      Safety Authority (EFSA). This study reviews the perception of the NHCR of 14
      Dutch stakeholders to unravel the grounds for disproving the putative health
      claims. Most claims are shown to be refused based on the quality of scientific
      substantiation, due to usage of scientific methods on which no consensus has been
      reached and the differences in expectations and requirements. Three themes
      exemplify the need for improvement in applying the NHCR: (i) enforcement; (ii)
      methodology; and (iii) perceived impact of the NHCR. With highly diverging
      perceptions of stakeholders, the current effectiveness of the NHCR can be
      questioned. The views of different stakeholders on these themes help to focus the
      discussion on the NCHR in capturing health effects. 

PMID- 25582176
TI  - Supplementation of omega 3 fatty acids improves oxidative stress in activated BV2
      microglial cell line.
AB  - Many reports have shown promising beneficial effects of long-chain
      polyunsaturated fatty acids (L-PUFAs) of the omega 3 series in several brain
      diseases. In the present study, we tested the hypothesis that omega 3 fatty acids
      supplement reduced pro-inflammatory functions in vitro and in vivo. We
      demonstrated that a supplement rich in PUFAs (SRP) increased cell viability in a
      dose-dependent manner suggesting its protective role against lipopolysaccharide
      (LPS)-induced cell death in BV2 microglial cell line. In the same cultures, the
      supplement rich in PUFAs reduced the reactive oxygen species (ROS) and nitric
      oxide (NO) production. A most prominent target for ROS management is the family
      of peroxisome proliferator-activated receptors (PPARs). The co-treatment with SRP
      and LPS increased significantly the nuclear immunoreactivity of PPAR-gammawhen
      compared the LPS treatment alone. Moreover, the chronic administration of the SRP
      in rats, increased the immunoreactivity of the PPAR-gamma1 protein confirming its
      potential neuroprotective effect. 

PMID- 25582177
TI  - A rapid and underivatized method for the determination of glutamine in human
      serum with ultra performance liquid chromatography-tandem mass spectrometry and
      its application.
AB  - A rapid and underivatized method for the determination of glutamine (Gln) in
      human serum was developed using ultra performance liquid chromatography tandem
      mass spectrometry (UPLC/MS/MS). Gln was eluted in an Acquity UPLC BEH Amid
      column. The chromatographic separation was performed with an isocratic mobile
      phase consisting of acetonitrile and ammonium formate. The analyses were carried
      out by select reaction monitoring using the precursor-to-product combinations of
      m/z 146.8->83.6 (Gln) and m/z 103.4->57.7 (IS). Validation results indicated that
      the lower limit of quantification was 30 MUg mL(-1) and the assay exhibited a
      linear range of 30-600 MUg mL(-1). A typical equation for the calibration curve
      was y = 0.0039 x + 0.0139 (r(2 )= 0.9992). The intra-batch precision (relative
      standard deviation, RSD) was less than 5.4% and inter-batch (RSD) was less than
      9.2%, while accuracy was from 93.11 to 101.39% and from 96.22 to 99.62%,
      determined from quality control (QC) samples for Gln. Then the established method
      was successfully applied to determine the Gln concentration in the serum of
      healthy human and pregnant woman within three-month pregnancy. The results showed
      that the Gln concentration in pregnant woman serum was generally lower than the
      healthy human group. It suggests that the pregnant woman should eat more food
      packed with Gln.

PMID- 25582178
TI  - Total antioxidant capacity, total phenolic content and iron and zinc
      dialyzability in selected Greek varieties of table olives, tomatoes and legumes
      from conventional and organic farming.
AB  - The objective was to compare 10 types of table olives, 11 types of tomatoes and
      tomato products and 18 types of legumes from conventional or organic farming for
      selected nutritional properties. All products were tested for their total
      antioxidant capacity (TAC) (Ferric Reducing Antioxidant Power (FRAP) assay) and
      total phenolic content (Folin-Ciocalteau method). Tomatoes and legumes were
      further tested for iron and zinc dialyzability after in vitro digestion. Ascorbic
      acid content of tomatoes was also measured. The study resulted that the
      nutritional properties of olives, tomatoes and legumes tested were different
      among the various cultivars but, in most cases, not between products from organic
      or conventional farming. Natural black olives, cherry and santorini tomatoes and
      lentils exhibited superior nutritional properties. 

PMID- 25582179
TI  - Development of a loop-mediated isothermal amplification (LAMP) assay for rapid
      and specific detection of common genetically modified organisms (GMOs).
AB  - Here, we developed a loop-mediated isothermal amplification (LAMP) assay for 11
      common transgenic target DNA in GMOs. Six sets of LAMP primer candidates for each
      target were designed and their specificity, sensitivity, and reproductivity were
      evaluated. With the optimized LAMP primers, this LAMP assay was simply run within
      45-60 min to detect all these targets in GMOs tested. The sensitivity,
      specificity, and reproductivity of the LAMP assay were further analyzed in
      comparison with those of Real-Time PCR. In consistent with real-time PCR,
      detection of 0.5% GMOs in equivalent background DNA was possible using this LAMP
      assay for all targets. In comparison with real-time PCR, the LAMP assay showed
      the same results with simple instruments. Hence, the LAMP assay developed can
      provide a rapid and simple approach for routine screening as well as specific
      events detection of many GMOs.

PMID- 25582180
TI  - Catechins in tea suppress the activity of cytochrome P450 1A1 through the aryl
      hydrocarbon receptor activation pathway in rat livers.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons
      (HAHs) develop various adverse effects through activation of an aryl hydrocarbon
      receptor (AhR). The suppressive effects of brewed green tea and black tea on 3
      methylcholanthrene (MC)-induced AhR activation and its downstream events were
      examined in the liver of rats. Ad-libitum drinking of green tea and black tea
      suppressed MC-induced AhR activation and elevation of ethoxyresorufin O
      deethylase activity in the liver, whereas the teas themselves did not induce
      them. Tea showed a suppressive fashion on the expression of cytochrome P450 1A1
      (CYP1A1). Tea suppressed the AhR activation induced by 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) ex vivo. A part of catechins and theaflavins was present in
      plasma and liver as conjugated and intact forms. The results of this study
      suggested that active component(s) of tea are incorporated in the liver and
      suppress the activity of CYP1As through the AhR activation pathway. 

PMID- 25582181
TI  - Vaccinium myrtillus extract prevents or delays the onset of diabetes--induced
      blood-retinal barrier breakdown.
AB  - Many dietary supplements have been sold through advertising their large number of
      beneficial effects. The aim of this study was to determine whether bilberries
      (Vaccinium myrtillus) help to prevent diabetes-induced retinal vascular
      dysfunction in vivo. V. myrtillus extract (VME; 100 mg/kg) was orally
      administered to streptozotocin-induced diabetic rats for 6 weeks. All diabetic
      rats exhibited hyperglycemia, and VME did not affect the blood glucose levels and
      body weight during the experiments. In the fluorescein-dextran angiography, the
      fluorescein leakage was significantly reduced in diabetic rats treated with VME.
      VME treatment also decreased markers of diabetic retinopathy, such as retinal
      vascular endothelial growth factor (VEGF) expression and degradation of zonula
      occludens-1, occludin and claudin-5 in diabetic rats. In conclusion, VME may
      prevent or delay the onset of early diabetic retinopathy. These findings have
      important implications for prevention of diabetic retinopathy using a dietary
      bilberry supplement. 

PMID- 25582183
TI  - Effect of soaking and fermentation on content of phenolic compounds of soybean
      (Glycine max cv. Merit) and mung beans (Vigna radiata [L] Wilczek).
AB  - Mung beans (Vigna radiata [L] Wilczek) purchased from a Spanish company as "green
      soybeans", showed a different phenolic composition than yellow soybeans (Glycine
      max cv. Merit). Isoflavones were predominant in yellow soybeans, whereas they
      were completely absent in the green seeds on which flavanones were predominant.
      In order to enhance their health benefits, both types of bean were subjected to
      technological processes, such as soaking and fermentation. Soaking increased
      malonyl glucoside isoflavone extraction in yellow beans and produced an increase
      in apigenin derivatives in the green beans. Lactobacillus plantarum CECT 748 T
      fermentation produced an increase in the bioactivity of both beans since a
      conversion of glycosylated isoflavones into bioactive aglycones and an increase
      of the bioactive vitexin was observed in yellow and green beans, respectively. In
      spite of potential consumer confusion, since soybean and "green soybean" are
      different legumes, the health benefits of both beans were enhanced by lactic
      fermentation. 

PMID- 25582184
TI  - Chemical Changes in Grape Stem and Their Relationship to Stem Color throughout
      Berry Ripening in Vitis vinifera L. cv Shiraz.
AB  - Little attention has been paid to the color change or chemical compositional
      changes that occur in grape stems and how this correlates with the berry ripening
      process. Recently we have found that the change in grape peduncle color of Shiraz
      (Vitis vinifera) from green at veraison to predominantly brown at harvest occurs
      in parallel with berry ripening and as such may represent a new way of assisting
      in the prediction of grape maturity and harvest date. We have now investigated
      further the link between certain key chemical compositional changes that occur in
      the grape stem (peduncle and rachis) from veraison to harvest and how these
      attributes correlate with the observed color change in the vineyard. We report
      that peduncle moisture content has an excellent linear correlation with the color
      hue value and is negatively correlated in a strong fashion with the chlorophyll
      and carotenoid pigment ratio (Ca+b/Cx+c) within the peduncles. Significant
      differences in the moisture content, total chlorophylls (including chlorophyll a
      and b levels), total carotenoids, total phenolics, and the antioxidant capacity
      (DPPH) levels between the peduncles and rachises were found as they evolve from
      veraison to harvest. Finally, we have demonstrated for the first time that
      peduncle moisture content codevelops with the prototypical berry ripeness
      parameters (oBrix, pH, TA), which provides for the development of a new approach
      for viticulturists and winemakers to evaluate grape ripeness through peduncle
      moisture levels and therefore assist in harvest decision making.

PMID- 25582182
TI  - Single high-dose vitamin D at birth corrects vitamin D deficiency in infants in
      Mexico.
AB  - This study examined the prevalence of vitamin D deficiency in mothers and infants
      in Tijuana, Mexico and determined the effect of a single oral dose of 50,000 IU
      vitamin D3 at birth on 25-hydroxyvitamin D (25[OH]D) levels during infancy.
      Healthy infants were randomized to receive vitamin D3 or placebo at birth. At
      birth 23% of infants were vitamin D deficient and 77% had vitamin D insufficiency
      (mean 25[OH]D level 18.9 ng/ml); 10% of mothers were vitamin D deficient and 61%
      were insufficient. Infants receiving vitamin D3 had higher 25(OH)D levels at two
      months (N = 29; 33.9 versus 24.2 ng/ml) and six months (N = 21; 36.5 versus 27.4
      ng/ml). Exclusively breastfed infants had lower 25(OH)D levels at two months
      (14.9 versus 33.4 ng/ml). Vitamin D deficiency is common in infants and mothers
      in Tijuana, Mexico. A single dose of vitamin D3 at birth was safe and
      significantly increased 25(OH)D levels during infancy.

PMID- 25582186
TI  - New therapies in non-Hodgkin lymphoma.
AB  - Non-Hodgkin lymphomas are among the most prevalent hematologic malignancies.
      Although the addition of rituximab (R) to chemotherapy has made a big impact in
      the treatment of B cell lymphomas, most of them are not cured yet. The panorama
      in natural killer/T cell lymphomas is more unsatisfactory, thus representing a
      group of diseases where effective therapies constitute an urgent medical need. In
      recent years, several new antineoplastic agents have been tested in clinical
      trials showing promising results. The aim of this review is to update information
      of these studies that are already changing the scenario of the treatment of
      patients with Non-Hodgkin lymphoma. 

PMID- 25582185
TI  - Family dynamics and psychosocial functioning in children with SCI/D from
      Colombia, South America.
AB  - OBJECTIVE: The purpose of this study was to examine the connections between
      family dynamics and the psychosocial functioning of children with spinal cord
      injuries and disorders (SCI/D). DESIGN: Cross-sectional. SETTING: Participants
      were recruited from communities in Neiva, Colombia. PARTICIPANTS: Thirty children
      with SCI/D and their primary caregiver participated. Children were between 8 and
      17 years of age, and had sustained their injury at least six months prior to data
      collection. INTERVENTIONS: NA. OUTCOME MEASURES: Participating children completed
      measures assessing their own psychosocial functioning (Children's Depression
      Inventory, Revised Children's Manifest Anxiety Scale-2, Pediatric Quality of Life
      Inventory), and their primary caregiver completed measures of family dynamics
      (Family Adaptability and Cohesion Evaluation Scale- Fourth Edition, Family
      Communication Scale, Family Assessment Device- General Functioning, Family
      Satisfaction Scale, Relationship-Focused Coping Scale). RESULTS: A correlation
      matrix showed a number of significant bivariate correlations between child and
      family variables, and three multiple regressions showed that family satisfaction,
      empathy, and flexibility significantly explained 27% of the variance in child
      worry; family satisfaction and communication explained 18% of the variance in
      child social anxiety; and family cohesion and communication explained 23% of the
      variance in child emotional functioning. CONCLUSIONS: These findings highlight
      the importance of rehabilitation professionals considering the association
      between family dynamics and the psychosocial functioning of children with SCI/D
      when working with this population.

PMID- 25582187
TI  - Validation of signalling pathways: Case study of the p16-mediated pathway.
AB  - p16 is recognized as a tumor suppressor gene due to the prevalence of its genetic
      inactivation in all types of human cancers. Additionally, p16 gene plays a
      critical role in controlling aging, regulating cellular senescence, detection and
      maintenance of DNA damage. The molecular mechanism behind these events involves
      p16-mediated signaling pathway (or p16- Rb pathway), the focus of our study.
      Understanding functional dependence between dynamic behavior of biological
      components involved in the p16-mediated pathway and aforesaid molecular-level
      events might suggest possible implications in the diagnosis, prognosis and
      treatment of human cancer. In the present work, we employ reverse-engineering
      approach to construct the most detailed computational model of p16-mediated
      pathway in higher eukaryotes. We implement experimental data from the literature
      to validate the model, and under various assumptions predict the dynamic behavior
      of p16 and other biological components by interpreting the simulation results.
      The quantitative model of p16-mediated pathway is created in a systematic manner
      in terms of Petri net technologies. 

PMID- 25582188
TI  - Acute and chronic rejection: compartmentalization and kinetics of
      counterbalancing signals in cardiac transplants.
AB  - Acute and chronic rejection impact distinct compartments of cardiac allografts.
      Intramyocardial mononuclear cell infiltrates define acute rejection, whereas
      chronic rejection affects large arteries. Hearts transplanted from male to female
      C57BL/6 mice undergo acute rejection with interstitial infiltrates at 2 weeks
      that resolve by 6 weeks when large arteries develop arteriopathy. These processes
      are dependent on T cells because no infiltrates developed in T cell-deficient
      mice and transfer of CD4 T cells restored T cell as well as macrophage
      infiltrates and ultimately neointima formation. Markers of inflammatory
      macrophages were up-regulated in the interstitium acutely and decreased as
      markers of wound healing macrophages increased chronically. Programmed cell death
      protein, a negative costimulator, and its ligand PDL1 were up-regulated in the
      interstitium during resolution of acute rejection. Blocking PDL1:PD1 interactions
      in the acute phase increased interstitial T cell infiltrates. Toll-like receptor
      (TLR) 4 and its endogenous ligand hyaluronan were increased in arteries with
      neointimal expansion. Injection of hyaluronan fragments increased intragraft
      production of chemokines. Our data indicate that negative costimulatory pathways
      are critical for the resolution of acute interstitial infiltrates. In the
      arterial compartment recognition of endogenous ligands including hyaluronan by
      the innate TLRs may support the progression of arteriopathy. 

PMID- 25582189
TI  - Adverse reaction to metal debris after Birmingham hip resurfacing arthroplasty.
AB  - BACKGROUND AND PURPOSE: Concern has emerged about local soft-tissue reactions
      after hip resurfacing arthroplasty (HRA). The Birmingham Hip Resurfacing (BHR)
      was the most commonly used HRA device at our institution. We assessed the
      prevalence and risk factors for adverse reaction to metal debris (ARMD) with this
      device. PATIENTS AND METHODS: From 2003 to 2011, BHR was the most commonly used
      HRA device at our institution, with 249 implantations. We included 32 patients
      (24 of them men) who were operated with a BHR HRA during the period April 2004 to
      March 2007 (42 hips; 31 in men). The mean age of the patients was 59 (26-77)
      years. These patients underwent magnetic resonance imaging (MRI), serum metal ion
      measurements, the Oxford hip score questionnaire, and physical examination. The
      prevalence of ARMD was recorded, and risk factors for ARMD were assessed using
      logistic regression models. The mean follow-up time was 6.7 (2.4-8.8) years.
      RESULTS: 6 patients had a definite ARMD (involving 9 of the 42 hips). 8 other
      patients (8 hips) had a probable ARMD. Thus, there was definite or probable ARMD
      in 17 of the 42 hips. 4 of 42 hips were revised for ARMD. Gender, bilateral metal
      on-metal hip replacement and head size were not factors associated with ARMD.
      INTERPRETATION: We found that HRA with the Birmingham Hip Resurfacing may be more
      dangerous than previously believed. We advise systematic follow-up of these
      patients using metal ion levels, MRI/ultrasound, and patient-reported outcome
      measures.

PMID- 25582190
TI  - Characterization of Helicobacter pylori HP0231 (DsbK): role in disulfide bond
      formation, redox homeostasis and production of Helicobacter cystein-rich protein
      HcpE.
AB  - Helicobacter pylori is a human gastric pathogen that colonizes ~ 50% of the
      world's population. It can cause gastritis, gastric or duodenal ulcers and also
      gastric cancer. The numerous side effects of available treatments and the
      emergence of antibiotic resistant strains are severe concerns that justify
      further research into H. pylori's pathogenic mechanisms. H. pylori produces
      secreted proteins that may play a role in virulence, including the Helicobacter
      cysteine-rich protein HcpE (aka HP0235). We demonstrate herein that HcpE is
      secreted in the culture supernatant both as a soluble protein and in association
      with outer membrane vesicles. We show that the structure of HcpE comprises an
      organized array of disulfide bonds. We identify DsbK (aka HP0231) as a folding
      factor necessary for HcpE production and secretion in H. pylori and show that
      recombinant DsbK can interact with and refold unprocessed, reduced HcpE in vitro.
      These experiments highlight the first biologically relevant substrate for DsbK.
      Furthermore, we show that DsbK has disulfide bond (Dsb) forming activity on
      reduced lysozyme and demonstrate a DsbA-type of activity for DsbK upon expression
      in E. coli, despite its similarity with DsbG. Finally, we show a role of DsbK in
      maintaining redox homeostasis in H. pylori. 

PMID- 25582191
TI  - The tomato res mutant which accumulates JA in roots in non-stressed conditions
      restores cell structure alterations under salinity.
AB  - Jasmonic acid (JA) regulates a wide spectrum of plant biological processes, from
      plant development to stress defense responses. The role of JA in plant response
      to salt stress is scarcely known, and even less known is the specific response in
      root, the main plant organ responsible for ionic uptake and transport to the
      shoot. Here we report the characterization of the first tomato (Solanum
      lycopersicum) mutant, named res (restored cell structure by salinity), that
      accumulates JA in roots prior to exposure to stress. The res tomato mutant
      presented remarkable growth inhibition and displayed important morphological
      alterations and cellular disorganization in roots and leaves under control
      conditions, while these alterations disappeared when the res mutant plants were
      grown under salt stress. Reciprocal grafting between res and wild type (WT)
      (tomato cv. Moneymaker) indicated that the main organ responsible for the
      development of alterations was the root. The JA-signaling pathway is activated in
      res roots prior to stress, with transcripts levels being even higher in control
      condition than in salinity. Future studies on this mutant will provide
      significant advances in the knowledge of JA role in root in salt-stress tolerance
      response, as well as in the energy trade-off between plant growth and response to
      stress. 

PMID- 25582192
TI  - Severe and fulminant hepatitis of indeterminate etiology in a Japanese center.
AB  - AIM: The outcome of acute liver failure (ALF) is influenced by its etiology,
      making etiological consideration of ALF important. However, specific etiology
      could not be identified in 30-40% of adult patients in a Japanese nationwide
      survey. We examined our patients with severe (SH) and fulminant hepatitis (FH) of
      indeterminate etiology for the better understanding of ALF. METHODS: We
      investigated 106 adult patients with SH or FH including 24 of indeterminate
      etiology between 2000 and 2013, retrospectively. RESULTS: Of 24 patients, 12 were
      men. Seventeen were SH and seven FH (three FH acute type and four FH subacute
      type). Eighty-three percent of patients were positive for antinuclear antibody.
      Seventeen recovered without liver transplantation (LT), two received LT and five
      died without LT. Histology of 15 patients showed a pattern of acute hepatitis
      (massive necrosis in four, submassive necrosis in one, severe acute hepatitis in
      two and acute hepatitis in eight). The involvement of immune-mediated liver
      injury was histologically suggested in some patients. CONCLUSION: There was no
      large cluster of etiology in our patients with indeterminate cause. The causes of
      ALF of indeterminate etiology were the mixture of various minor or rare ones, if
      precise diagnosis of acute AIH was done. Outcome of our patients with
      indeterminate cause was not poor if they were treated as early as possible after
      the diagnosis of severe disease. Careful examination of unknown viral infection,
      drugs, toxins, undefined metabolic disorders and histology may help detect some
      of these etiologies.

PMID- 25582193
TI  - A clinical review of the pathophysiology, diagnosis, and treatment of pyothorax
      in dogs and cats.
AB  - OBJECTIVE: To review the current literature in reference to the pathophysiology,
      diagnosis, and treatment of pyothorax in dogs and cats. ETIOLOGY: Pyothorax, also
      known as thoracic empyema, is characterized by the accumulation of septic
      purulent fluid within the pleural space. While the actual route of pleural
      infection often remains unknown, the oral cavity and upper respiratory tract
      appear to be the most common source of microorganisms causing pyothorax in dogs
      and cats. In human medicine, pyothorax is a common clinical entity associated
      with bacterial pneumonia and progressive parapneumonic effusion. DIAGNOSIS:
      Thoracic imaging can be used to support a diagnosis of pleural effusion, but
      cytologic examination or bacterial culture of pleural fluid are necessary for a
      definitive diagnosis of pyothorax. THERAPY: The approach to treatment for
      pyothorax varies greatly in both human and veterinary medicine and remains
      controversial. Treatment of pyothorax has classically been divided into medical
      or surgical therapy and may include administration of antimicrobials,
      intermittent or continuous thoracic drainage, thoracic lavage, intrapleural
      fibrinolytic therapy, video-assisted thoracic surgery, and traditional
      thoracostomy. Despite all of the available options, the optimal treatment to
      ensure successful short- and long-term outcome, including the avoidance of
      recurrence, remains unknown. PROGNOSIS: The prognosis for canine and feline
      pyothorax is variable but can be good with appropriate treatment. A review of the
      current veterinary literature revealed an overall reported survival rate of 83%
      in dogs and 62% in cats. As the clinical presentation of pyothorax in small
      animals is often delayed and nonspecific, rapid diagnosis and treatment are
      required to ensure successful outcome.

PMID- 25582194
TI  - Pluripotency transcription factor Oct4 mediates stepwise nucleosome demethylation
      and depletion.
AB  - The mechanisms whereby the crucial pluripotency transcription factor Oct4
      regulates target gene expression are incompletely understood. Using an assay
      system based on partially differentiated embryonic stem cells, we show that Oct4
      opposes the accumulation of local H3K9me2 and subsequent Dnmt3a-mediated DNA
      methylation. Upon binding DNA, Oct4 recruits the histone lysine demethylase
      Jmjd1c. Chromatin immunoprecipitation (ChIP) time course experiments identify a
      stepwise Oct4 mechanism involving Jmjd1c recruitment and H3K9me2 demethylation,
      transient FACT (facilitates chromatin transactions) complex recruitment, and
      nucleosome depletion. Genome-wide and targeted ChIP confirms binding of newly
      synthesized Oct4, together with Jmjd1c and FACT, to the Pou5f1 enhancer and a
      small number of other Oct4 targets, including the Nanog promoter. Histone
      demethylation is required for both FACT recruitment and H3 depletion. Jmjd1c is
      required to induce endogenous Oct4 expression and fully reprogram fibroblasts to
      pluripotency, indicating that the assay system identifies functional Oct4
      cofactors. These findings indicate that Oct4 sequentially recruits activities
      that catalyze histone demethylation and depletion. 

PMID- 25582195
TI  - The zinc finger protein ZNF658 regulates the transcription of genes involved in
      zinc homeostasis and affects ribosome biogenesis through the zinc transcriptional
      regulatory element.
AB  - We previously identified the ZTRE (zinc transcriptional regulatory element) in
      genes involved in zinc homeostasis and showed that it mediates transcriptional
      repression in response to zinc. We now report that ZNF658 acts at the ZTRE.
      ZNF658 was identified by matrix-assisted laser desorption ionization-time of
      flight mass spectrometry of a band excised after electrophoretic mobility shift
      assay using a ZTRE probe. The protein contains a KRAB domain and 21 zinc fingers.
      It has similarity with ZAP1 from Saccharomyces cerevisiae, which regulates the
      response to zinc restriction, including a conserved DNA binding region we show to
      be functional also in ZNF658. Small interfering RNA (siRNA) targeted to ZNF658
      abrogated the zinc-induced, ZTRE-dependent reduction in SLC30A5 (ZnT5 gene),
      SLC30A10 (ZnT10 gene), and CBWD transcripts in human Caco-2 cells and the ability
      of zinc to repress reporter gene expression from corresponding promoter-reporter
      constructs. Microarray analysis of the effect of reducing ZNF658 expression by
      siRNA uncovered a large decrease in rRNA. We find that ZTREs are clustered within
      the 45S rRNA precursor. We also saw effects on expression of multiple ribosomal
      proteins. ZNF658 thus links zinc homeostasis with ribosome biogenesis, the most
      active transcriptional, and hence zinc-demanding, process in the cell. ZNF658 is
      thus a novel transcriptional regulator that plays a fundamental role in the
      orchestrated cellular response to zinc availability. 

PMID- 25582196
TI  - Dynamic switching of active promoter and enhancer domains regulates Tet1 and Tet2
      expression during cell state transitions between pluripotency and
      differentiation.
AB  - The Tet 5-methylcytosine dioxygenases catalyze DNA demethylation by producing 5
      hydroxymethylcytosine and further oxidized products. Tet1 and Tet2 are highly
      expressed in mouse pluripotent cells and downregulated to different extents in
      somatic cells, but the transcriptional mechanisms are unclear. Here we defined
      the promoter and enhancer domains in Tet1 and Tet2. Within a 15-kb
      "superenhancer" of Tet1, there are two transcription start sites (TSSs) with
      different activation patterns during development. A 6-kb promoter region upstream
      of the distal TSS is highly active in naive pluripotent cells, autonomously
      reports Tet1 expression in a transgenic system, and rapidly undergoes DNA
      methylation and silencing upon differentiation in cultured cells and native
      epiblast. A second TSS downstream, associated with a constitutively weak CpG-rich
      promoter, is activated by a neighboring enhancer in naive embryonic stem cells
      (ESCs) and primed epiblast-like cells (EpiLCs). Tet2 has a CpG island promoter
      with pluripotency-independent activity and an ESC-specific distal intragenic
      enhancer; the latter is rapidly downregulated in EpiLCs. Our study reveals
      distinct modes of transcriptional regulation at Tet1 and Tet2 during cell state
      transitions of early development. New transgenic reporters using Tet1 and Tet2
      cis-regulatory domains may serve to distinguish nuanced changes in pluripotent
      states and the underlying epigenetic variations. 

PMID- 25582197
TI  - The ubiquitin E3 ligase SCF-FBXO24 recognizes deacetylated nucleoside diphosphate
      kinase A to enhance its degradation.
AB  - The Skp-Cul-F box (SCF) ubiquitin E3 ligase machinery recognizes predominantly
      phosphodegrons or, less commonly, an (I/L)Q molecular signature within substrates
      to facilitate their recruitment in mediating protein ubiquitination and
      degradation. Here, we examined the molecular signals that determine the turnover
      of the multifunctional enzyme nucleoside diphosphate kinase A (NDPK-A) that
      controls cell proliferation. NDPK-A protein exhibits a half-life of ~6 h in HeLa
      cells and is targeted for ubiquitylation through actions of the F-box protein
      FBXO24. SCF-FBXO24 polyubiquitinates NDPK-A at K85, and two NH(2)-terminal
      residues, L55 and K56, were identified as important molecular sites for FBXO24
      interaction. Importantly, K56 acetylation impairs its interaction with FBXO24,
      and replacing K56 with Q56, an acetylation mimic, reduces NDPK-A FBXO24 binding
      capacity. The acetyltransferase GCN5 catalyzes K56 acetylation within NDPK-A,
      thereby stabilizing NDPK-A, whereas GCN5 depletion in cells accelerates NDPK-A
      degradation. Cellular expression of an NDPK-A acetylation mimic or FBXO24
      silencing increases NDPK-A life span which, in turn, impairs cell migration and
      wound healing. We propose that lysine acetylation when presented in the
      appropriate context may be recognized by some F-box proteins as a unique
      inhibitory molecular signal for their recruitment to restrict substrate
      degradation.

PMID- 25582198
TI  - Role of microRNA 30a targeting insulin receptor substrate 2 in colorectal
      tumorigenesis.
AB  - MicroRNAs (miRNAs) are dysregulated in many types of malignant diseases,
      including colorectal cancer. miRNA 30a (miR-30a) is a member of the miR-30 family
      and has been implicated in many types of cancers. In this study, we determined
      the expression of miR-30a in human colon cancer tissues and cell lines. miR-30a
      was found to be significantly downregulated in both the tissues and cell lines.
      Furthermore, overexpression of miR-30a inhibited, while silencing of miR-30a
      promoted, cell proliferation, migration, and invasion in vitro. Consistently,
      stable overexpression of miR-30a suppressed the growth of colon cancer cell
      xenografts in vivo. Moreover, bioinformatic algorithms and luciferase reporter
      assays revealed that insulin receptor substrate 2 (IRS2) is a direct target of
      miR-30a. Further functional studies suggested that repression of IRS2 by miR-30a
      partially mediated the tumor suppressor effect of miR-30a. In addition, miR-30a
      inhibited constitutive phosphorylation of Akt by targeting IRS2. Additionally,
      clinicopathological analysis indicated that miR-30a has an inverse correlation
      with the staging in patients with colon cancer. Taken together, our study
      provides the first evidence that miR-30a suppressed colon cancer cell growth
      through inhibition of IRS2. Thus, miR-30a might serve as a promising therapeutic
      strategy for colon cancer treatment. 

PMID- 25582199
TI  - Uncoupling lipid metabolism from inflammation through fatty acid binding protein
      dependent expression of UCP2.
AB  - Chronic inflammation in obese adipose tissue is linked to endoplasmic reticulum
      (ER) stress and systemic insulin resistance. Targeted deletion of the murine
      fatty acid binding protein (FABP4/aP2) uncouples obesity from inflammation
      although the mechanism underlying this finding has remained enigmatic. Here, we
      show that inhibition or deletion of FABP4/aP2 in macrophages results in increased
      intracellular free fatty acids (FFAs) and elevated expression of uncoupling
      protein 2 (UCP2) without concomitant increases in UCP1 or UCP3. Silencing of UCP2
      mRNA in FABP4/aP2-deficient macrophages negated the protective effect of FABP
      loss and increased ER stress in response to palmitate or lipopolysaccharide
      (LPS). Pharmacologic inhibition of FABP4/aP2 with the FABP inhibitor HTS01037
      also upregulated UCP2 and reduced expression of BiP, CHOP, and XBP-1s. Expression
      of native FABP4/aP2 (but not the non-fatty acid binding mutant R126Q) into
      FABP4/aP2 null cells reduced UCP2 expression, suggesting that the FABP-FFA
      equilibrium controls UCP2 expression. FABP4/aP2-deficient macrophages are
      resistant to LPS-induced mitochondrial dysfunction and exhibit decreased
      mitochondrial protein carbonylation and UCP2-dependent reduction in intracellular
      reactive oxygen species. These data demonstrate that FABP4/aP2 directly regulates
      intracellular FFA levels and indirectly controls macrophage inflammation and ER
      stress by regulating the expression of UCP2. 

PMID- 25582200
TI  - Otoferlin deficiency in zebrafish results in defects in balance and hearing:
      rescue of the balance and hearing phenotype with full-length and truncated forms
      of mouse otoferlin.
AB  - Sensory hair cells convert mechanical motion into chemical signals. Otoferlin, a
      six-C2 domain transmembrane protein linked to deafness in humans, is hypothesized
      to play a role in exocytosis at hair cell ribbon synapses. To date, however,
      otoferlin has been studied almost exclusively in mouse models, and no rescue
      experiments have been reported. Here we describe the phenotype associated with
      morpholino-induced otoferlin knockdown in zebrafish and report the results of
      rescue experiments conducted with full-length and truncated forms of otoferlin.
      We found that expression of otoferlin occurs early in development and is
      restricted to hair cells and the midbrain. Immunofluorescence microscopy revealed
      localization to both apical and basolateral regions of hair cells. Knockdown of
      otoferlin resulted in hearing and balance defects, as well as locomotion
      deficiencies. Further, otoferlin morphants had uninflated swim bladders. Rescue
      experiments conducted with mouse otoferlin restored hearing, balance, and
      inflation of the swim bladder. Remarkably, truncated forms of otoferlin retaining
      the C-terminal C2F domain also rescued the otoferlin knockdown phenotype, while
      the individual N-terminal C2A domain did not. We conclude that otoferlin plays an
      evolutionarily conserved role in vertebrate hearing and that truncated forms of
      otoferlin can rescue hearing and balance. 

PMID- 25582202
TI  - Donor-derived equine mesenchymal stem cells suppress proliferation of mismatched
      lymphocytes.
AB  - REASONS FOR PERFORMING STUDY: Recently, it has been shown that mesenchymal stem
      cells (MSCs) do not express the major histocompatibility complex (MHC) II antigen
      and are able to inhibit proliferation of MHC-mismatched stimulated lymphocytes,
      enabling their use as in vivo allogeneic transplants. However, prior to clinical
      application of allo-MSCs, in vitro tests are required to confirm the safety of
      treatment protocols. OBJECTIVES: To evaluate the immunosuppressive capabilities
      of equine bone-marrow-derived MSCs (BM-MSCs) on MHC-mismatched lymphocytes. STUDY
      DESIGN: In vitro experiment. METHODS: Phytohaemagglutinin-stimulated peripheral
      blood mononuclear cells (PBMCs) from 3 Thoroughbreds (recipients) were co
      cultured with mismatched BM-MSCs from 3 Connemara ponies (donors). Proliferation
      of lymphocytes was monitored by carboxyfluorescein succinimidyl ester labelling
      and analysed by flow cytometry. In total, 6 horses were haplotyped using
      microsatellites to confirm mismatching. Optimisation of the conditions to
      stimulate Thoroughbred lymphocytes and titration of equine anti-CD4 and anti-CD8
      antibodies were performed. Connemara pony and Thoroughbred BM-MSCs were isolated,
      expanded and characterised by tri-lineage differentiation. Finally, BM-MSCs from
      both breeds were set up in co-culture at different ratios with stimulated
      Thoroughbred lymphocytes. Proliferation of CD4(+) and CD8(+) cells was determined
      by flow cytometry. RESULTS: A high proportion of CD4/CD8 double-positive
      lymphocytes were found in freshly isolated PBMCs, although this percentage
      decreased after 4 days of culture. Mismatched BM-MSCs inhibited proliferation of
      stimulated lymphocytes in a dose-dependent manner, with the greatest suppression
      occurring at a 1:10 ratio of BM-MSCs to PBMCs. Proliferation of CD4(+) and CD8(+)
      subpopulations decreased in 1:10 co-culture, with statistical significance in the
      case of CD8(+) cells, while that of the CD4/CD8 double-positive population was
      similar to the phytohaemagglutinin control. CONCLUSIONS: The results demonstrate
      dose-dependent immunosuppression of stimulated lymphocytes by mismatched equine
      BM-MSCs, supporting their future application in allo-MSC clinical treatments.

PMID- 25582203
TI  - [Ocular fundus disease in China: the current situation, progression, and issues
      to be resolved].
AB  - Ocular fundus disease is an important cause of blindness in China today. It has
      been a serious threat to people's health and quality of life. After unremitting
      efforts of generations, we have made remarkable achievements in the prevention,
      diagnosis, and treatment of ocular fundus disease. We have achieved many
      breakthroughs and progressions in the investigations of diabetic retinopathy,
      choroidal neovascularization, pediatric fundus disease, and other major diseases.
      And weare gradually standardizing imaging data management, new drug development
      procedures, and multi-center clinical trials. In the future, we need to further
      standardize the clinical diagnosis and treatment, to accelerate the basic
      research of serious and rare diseases, and to improve the overall level in the
      field of ocular fundus disease in China, so as to enhance our international
      influence in ophthalmology. 

PMID- 25582204
TI  - [The correlation between carotid stenosis detected by neck vascular ultrasound
      and branch retinal vein occlusion].
AB  - OBJECTIVE: To discuss the clinical significance of the neck vascular ultrasound
      examination in patients with branch retinal vein occlusion (BRVO). METHODS: Case
      control study. Thirty patients of BRVO and 30 healthy subjects with no ophthalmic
      and systemic symptoms were recruited from January 2010 to January 2012 in the
      Department of Ophthalmology of the First People's Hospital of Dali Prefecture.
      The neck vascular ultrasound examination was performed in two groups. The
      incidence of carotid atheromatous plaque, the rate of carotid stenosis and the
      carotid artery resistance index (RI) were compared using chi square test.
      Logistic regression analysis of the rate of carotid stenosis and carotid artery
      RI were performed. RESULTS: In BRVO group, 23 cases had carotid atheromatous
      plaque with the incidence of 76.7% Nineteen cases had carotid stenosis with the
      incidence of 63.3%. The average carotid artery RI was 0.66. In control group,
      carotid artery atheromatous plaque was found on 6 subjects with incidence of
      20.0%. Carotid artery stenosis was detected in 3 subjects with incidence of
      10.0%. The average carotid artery RI was 0.61. The incidence of carotid artery
      atheromatous plaque and carotid stenosis and carotid artery RI in BRVO group were
      significantly higher than the control group. The difference was statistically
      significant (P < 0.05). Logistic regression analysis showed that carotid artery
      stenosis (partial regression coefficien t = 2.263, OR = 9.611, P = 0.004) and
      carotid artery RI (partial regression coefficien t = 23.713, OR = 669.273, P =
      0.006) had influence in BRVO patients as risk factors. CONCLUSION: Early
      detection of carotid scleratheroma and carotid artery stenosis by the carotid
      artery ultrasound examination played an important role in prevention or treatment
      of BRVO.

PMID- 25582205
TI  - [Etiology and pathogens of fungal endophthalmitis].
AB  - OBJECTIVE: To evaluate epidemiologic features and laboratory findings of fungal
      endophthalmitis in north China. METHODS: Eighty-one patients (81 eyes) were
      diagnosed with fungal endophthalmitis at our institution from January 2000 to
      December 2012. Patient history, etiological agents, direct smear examination,
      fungal culture and pathogen sensitivity to antifungal drug were evaluated.
      RESULTS: The fungal endophthalmitis was exogenous in 73 cases (90.1%), among
      which 43 had fungal keratitis in which Fusarium was the first pathogen occupied
      88.4% (38 of 43 cases). Twenty seven of 73 cases (33.3%) occurred after
      penetrating ocular trauma and Aspergillus was the most common pathogens isolated
      in these cases (11 of 27; 40.7%). The left 3 cases were associated with ocular
      surgery. Four of the other eight eyes (9.9%) with endogenous infection had
      association with drug abuse. Aspergillus was the main isolated pathogens from the
      endogenous fungal endophthalmitis (4 of 8 cases). Hyphae were found in 52 (77.6%)
      of 67 smear samples by direct microscopic examination. Fungal pathogens cultured
      from 81 samples were identified as 10 genera and 18 species; Fusarium accounted
      for 60.5% (49 eyes), Aspergillus for 21.0% (17 eyes) and Candida for 6.2% (5/81).
      The total sensitive rate of Fusarium and Aspergillus in vitro to voriconazole,
      amphotericin B, ketconazole, itraconazole and fluconazole was 84.7% (33/39),
      71.8% (28/39), 43.6% (17/39), 17.9% (7/39) and 7.7% (3/39) respectively.
      CONCLUSIONS: Fungal endophthalmitis in north China is predominantly exogenous.
      Fungal keratitis and penetrating trauma are the main common etiological factors.
      Fusarium ranks first in pathogens, followed by Aspergillus and Candida. Fusarium
      was the first pathogen of exogenous fungal endophthalmitis caused by fungal
      keratitis. Aspergillus was the most common isolated pathogens from exogenous
      fungal endophthalmitis caused by penetrating ocular trauma and it also was the
      first pathogen of endogenous fungal endophthalmitis. Microscopic detection of
      hyphae from samples is helpful in the diagnosis. Fusarium ranks first in
      pathogens, followed by Aspergillus. They both are more sensitive to voriconazole
      and amphotericin B than ketconazole, fluconazole and itraconazole.

PMID- 25582201
TI  - Regulation of endothelial cell proliferation and vascular assembly through
      distinct mTORC2 signaling pathways.
AB  - Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates
      a diverse array of cellular processes, including cell growth, survival,
      metabolism, and cytoskeleton dynamics. mTOR functions in two distinct complexes,
      mTORC1 and mTORC2, whose activities and substrate specificities are regulated by
      complex specific cofactors, including Raptor and Rictor, respectively. Little is
      known regarding the relative contribution of mTORC1 versus mTORC2 in vascular
      endothelial cells. Using mouse models of Raptor or Rictor gene targeting, we
      discovered that Rictor ablation inhibited vascular endothelial growth factor
      (VEGF)-induced endothelial cell proliferation and assembly in vitro and
      angiogenesis in vivo, whereas the loss of Raptor had only a modest effect on
      endothelial cells (ECs). Mechanistically, the loss of Rictor reduced the
      phosphorylation of AKT, protein kinase Calpha (PKCalpha), and NDRG1 without
      affecting the mTORC1 pathway. In contrast, the loss of Raptor increased the
      phosphorylation of AKT despite inhibiting the phosphorylation of S6K1, a direct
      target of mTORC1. Reconstitution of Rictor-null cells with myristoylated AKT (Myr
      AKT) rescued vascular assembly in Rictor-deficient endothelial cells, whereas
      PKCalpha rescued proliferation defects. Furthermore, tumor neovascularization in
      vivo was significantly decreased upon EC-specific Rictor deletion in mice. These
      data indicate that mTORC2 is a critical signaling node required for VEGF-mediated
      angiogenesis through the regulation of AKT and PKCalpha in vascular endothelial
      cells. 

PMID- 25582206
TI  - [The effect of blue light on human retinal pigment epithelium cells alpha1D
      subunit protein expression and vascular endothelial growth factor and basic
      fibroblast growth factor secretion in vitro].
AB  - OBJECTIVE: To investigate the effect of blue light on human retinal pigment
      epithelium (RPE) alpha1D subunit protein expression and its relationship with
      vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) secretion in vitro. METHODS: The fourth generation cultured human RPE
      cells in vitro were randomly divided into 4 groups, group A (control), group B
      (exposure to blue light), group C (exposure to blue light+nifedipine), group D
      [exposure to blue light+(-)Bay K8644]. Cells were exposed to blue light (2 000 +/
      500) lx for 6 hours, and cells culture completed 24 hours later. VEGF and bFGF
      concentration were assayed by enzyme linked immunosorbent assay (ELISA). Real
      time polymerase chain reaction was used to analysis L-type calcium channel
      alpha1D subunit mRNA expression. Western blot was used to examine the protein
      expression of L-type calcium channel alpha1D subunit. Analysis of variance was
      used to compare the difference of alpha1D subunit mRNA and protein expression,
      VEGF and bFGF concentration between groups. Correlation analysis was used to show
      the relationship between alpha1D subunit protein expression and concentration of
      VEGF and bFGF. RESULTS: (1) There is significant statistically difference in the
      population mean of VEGF and bFGF concentration in four groups (F = 99.441,
      21.310, P = 0.000,0.000) . VEGF and bFGF concentration in group B (3 281.51 +/-
      251.73, 1 346.81 +/- 62.27) and group D (3 808.01 +/- 94.01, 1 485.82 +/- 108.97)
      was higher than it was in group A (2 401.09 +/- 228.07, 1 232.42 +/- 65.41) ,
      which was statistically different (P = 0.000, 0.000, 0.019, 0.000). And it was
      higher in group D (3 808.01 +/- 94.01, 1 485.82 +/- 108.97) compared with group B
      (3 281.51 +/- 251.73, 1 346.81 +/- 62.27) (P = 0.000, 0.006). While, it was lower
      in group C (1 927.28 +/- 143.11, 1 149.39 +/- 62.99) than it was in group B (3
      281.51 +/- 251.73, 1 346.81 +/- 62.27) (P = 0.000, 0.000) . (2) The mean of mRNA
      expression of alpha1D subunit between four groups was statistically significant
      (F = 50.320, P = 0.000) . It was higher in group B (210 +/- 23) , group D (478 +/
      80) and group C (232 +/- 14) than group A (100 +/- 20). It was statistically
      significant different (P = 0.023, 0.006, 0.010). And it was higher in group D
      (478 +/- 80) than group B (210 +/- 23) and C (232 +/- 14) (P = 0.032, 0.039). (3)
      There was statistically significant difference in the expression of L-type
      calcium channel alpha1D subunit protein in four groups (F = 1 940.363, P = 0.000)
      . It was significantly higher (P = 0.000,0.000) in group B (0.974 2 +/- 0.014 7)
      and group D (0.654 9 +/- 0.005 0) than group A (0.503 2 +/- 0.007 5). And it was
      higher in group D (0.654 9 +/- 0.005 0) than it was in group C (0.413 9 +/- 0.008
      8) (P = 0.000). (4) There was positive correlation between the L-type calcium
      channel alpha1D subunit protein expression and VEGF concentration secreted by
      retinal pigment epithelium cells (r = 0.674, F = 8.333, P = 0.016), but there was
      no correlation with bFGF concentration (r = 0.537, F = 4.061, P = 0.072).
      CONCLUSIONS: L-type calcium channel alpha1D subunit may be involved in blue light
      induced damage on human retinal pigment epithelial cells. Blue light exposure can
      induce the mRNA and protein expression of alpha1D subunit, VEGF and bFGF
      concentration in retinal pigment epithelium cells Increased. And there was a
      positive correlation between alpha1D subunit protein expression and the VEGF
      concentration.

PMID- 25582207
TI  - [The neuroprotection of brain-derived neurotrophic factor in experimental retinal
      detachment reattached].
AB  - OBJECTIVE: To investigate the effect of exogenous brain-derived neurotrophic
      factor (BDNF) on the retinal repair after experimental retinal detachment (RD)
      reattached. METHODS: Experimental study. Forty-eight normal rats were randomly
      divided into four groups:BDNF group, control group, RD reattached group and
      normal group. In order to detect the effects of BDNF on retinal degeneration
      caused by RD, the morphology of retina and the ultrastructure of retinal cells
      were observed by light microscopy and electron microscopy. The effect of BDNF on
      the apoptosis of retinal cells after RD reattached was detected by Terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      (TUNEL) technique. Data were analyzed using one-way analysis of variance (ANOVA)
      and secondary analysis for significance with independent-samples t-test. RESULTS:
      The average automatically reattached time was (31.3 +/- 3.5) days. Compared with
      control group, there were less damage in out segment and inner segment, more
      retinal cells in outer nuclear layer (ONL) and inner nuclear layer (INL), thicker
      ONL of retina and better organizational structure of retina in BDNF group. The
      average thickness of ONL and INL of retina were (21.166 +/- 3.087) um, (23.508 +/
      3.679) um respectively in BDNF group, and (16.084 +/- 2.928) um, (12.885 +/-
      3.070) um respectively in control group. The thickness of ONL and INL of retina
      showed a significant difference in BDNF group compared with control (P < 0.01).
      There were less TUNEL-positive cells in ONL of retina in BDNF group compared with
      control. CONCLUSIONS: This study indicates that the morphology of retina and the
      ultrastructure of retinal cells have changed, and the apoptosis of retinal cells
      are present after RD reattached. Exogenous BDNF can reduce retinal cells
      degeneration and inhibit the apoptosis of retinal cells and have a certain
      protection effects on the retinal damage caused by RD.

PMID- 25582208
TI  - [Effect of simvastatin on retinal Bcl-2/Bax expression and cell apoptosis in rats
      with ischemia-reperfusion injury].
AB  - OBJECTIVE: To explore the protective mechanism of simvastatin on retina ischemia
      reperfusion injury in a rat model. METHODS: It was a experiment study.One hundred
      and sixty-five adult male SD rats were randomly divided into three groups using
      digital table method, normal control group (CON, 55 rats), ischemia-reperfusion
      model group (MOD, 55 rats) and the medicine of simvastatin group (SIM, 55
      rats).Each group was divided into five points in time of 4 hours, 8 hours, 16
      hours, 24 hours and 48 hours, and there were 11 rats in each point. The right
      cephalic artery of each rat was clipped in model group and simvastatin group, but
      it was exposed in control group. Expression of Bcl-2 and Bax protein were
      determined by the immunohistochemical method, the number of cell apoptosis in
      retina were examined by the TUNEL method and express of Bcl-2 and Bax mRNA were
      measured by the real-time PCR method. The expression of proteins and mRNAs of Bcl
      2 and Bax and also apoptosis of the rat retinas in each group at corresponding
      time point are compared using single factor analysis of variance and LSD-t test.
      RESULTS: Expression of Bcl-2 protein in model group began to decline at 4 h,
      reached the lowest at 24 h, with the data of (0.192 +/- 0.011), (0.192 +/- 0.015)
      , (0.189 +/- 0.015), (0.183 +/- 0.012) and (0.187 +/- 0.010) .Expression of Bcl-2
      protein in simvastatin group were higher than model group at each time point,
      with the information of (0.208 +/- 0.011), (0.220 +/- 0.011) , (0.221 +/- 0.014),
      (0.228 +/- 0.007) and (0.206 +/- 0.015). The numbers were statistically
      significant at corresponding time point in each group (F(4, 8, 16, 24, 48) =
      8.079, 9.005, 9.904, 35.563, 8.810, P < 0.05). Expression of Bax protein in model
      group began to increased at 4 h, reached the highest at 24 h, with the data of
      (0.255 +/- 0.010), (0.261 +/- 0.033), (0.276 +/- 0.025), (0.324 +/- 0.037) and
      (0.234 +/- 0.018). Expression of Bax protein in simvastatin group were lower than
      model group at each time point, with the information of (0.222 +/- 0.012), (0.219
      +/- 0.017), (0.223 +/- 0.008), (0.232 +/- 0.021) and (0.214 +/- 0.008). The
      numbers were statistically significant at corresponding time point in each group
      (F(4, 8, 16, 24, 48) = 16.601, 13.525, 10.303, 25.849, 13.805, P < 0.05). AI of
      retina in model group began to increased at 4 h, reached the highest at 24 h,
      with the data of (11.771 +/- 0.722), (13.705 +/- 0.512), (15.533 +/- 0.370),
      (21.210 +/- 1.221) and (17.660 +/- 0.414). AI of retina in simvastatin group were
      lower than model group at each time point, with the information of (9.061 +/-
      0.289), (11.717 +/- 0.565), (13.506 +/- 0.541), (16.586 +/- 0.488) and (14.428 +/
      0.559). The numbers were statistically significant at corresponding time point
      in each group (F(4, 8, 16, 24, 48) = 87.096, 232.245, 575.564, 389.205, 771.658,
      P < 0.05). Bcl-2 mRNA in model group were lower than in control group at each
      time point, with the data of (0.360 +/- 0.017), (0.232 +/- 0.066), (0.314 +/-
      0.012), (0.179 +/- 0.019) and (0.357 +/- 0.084). But Bcl-2 mRNA in simvastatin
      group were higher than those in model group, with the information of (1.718 +/-
      0.247), (1.981 +/- 0.317), (1.309 +/- 0.031), (1.289 +/- 0.209) and (0.684 +/-
      0.071). The differences had statistical significance at corresponding time point
      in each group (F(4, 8, 16, 24, 48) = 112.934, 109.750, 3534.800, 112.428,
      128.140, P < 0.05). And Bax mRNA in the model group were higher than those in
      control group at each time point, with the data of (2.140 +/- 0.288), (3.189 +/-
      0.492), (2.896 +/- 0.466), (2.392 +/- 0.119) and (1.789 +/- 0.169). However, Bax
      mRNA in simvastatin group were lower than those in model group, with the
      information of (0.658 +/- 0.197), (1.746 +/- 0.315), (0.670 +/- 0.221), (0.952 +/
      0.164) and (0.575 +/- 0.174). The differences had statistical significance at
      corresponding time point in each group (F(4, 8, 16, 24, 48) = 74.115, 54.504,
      81.271, 243.743, 97.163, P < 0.05). CONCLUSIONS: Simvastatin has protective
      effects on retinal ischemia reperfusion injury, and the mechanism is closely
      related to inhibiting retinal cell apoptosis by adjusting the express of Bcl-2
      and Bax.

PMID- 25582209
TI  - [Evaluation the change of corneal epithelium thickness after pterygium excision
      with conjunctival autograft transplantation by Fourier domain optical coherence
      tomography].
AB  - OBJECTIVE: To evaluate the change of corneal epithelial thickness after pterygium
      excision with conjunctival autograft transplantation by Fourier Domain Optical
      Coherence Tomography (FD-OCT) . METHODS: Twenty-two patients (24 eyes) with the
      diagnosis of primary pterygium were enrolled. They underwent pterygium excision
      combined with conjunctival autograft transplantation. Twenty-five volunteers (25
      eyes) served as the normal control group. FD-OCT was performed preoperatively and
      1, 2, 3, 5, 7 days postoperatively to measure the thickness of corneal epithelium
      at 1 mm and 2 mm anterior to the nasal or temporal scleral spur. Corneal
      fluorescein staining was performed simultaneously. Comparisons on the thickness
      of corneal epithelium were made between preoperative values and postoperative
      ones. RESULTS: The thickness of cornea epithelium at 1 mm anterior to the scleral
      spur was (43.81 +/- 2.55) um in normal subjects. At day 1 after surgery, corneal
      epithelial thickness at the same location was (21.28 +/- 5.72) um and then
      gradually increased to (39.94 +/- 5.47) um at day 7 postoperatively. All the
      difference on postoperative days had statistically significant (t = -17.69, 
      14.97, -10.63, -9.86, -3.15, P < 0.05) . The thickness of cornea epithelium at 2
      mm anterior to the scleral spur was (40.50 +/- 3.17) um in normal subjects. At
      day 1 after surgery, corneal epithelial thickness at the same location was (24.02
      +/- 5.92) um, and then gradually increased to (940.34 +/- 5.69) um at day 7
      postoperatively. All the difference on postoperative days except day 7 had
      statistically significant (t = -12.08, -10.27, -6.18, -2.99, P < 0.05). Cornea
      epithelium at this location repaired sooner than that at 1 mm anterior to the
      scleral spur. At day 1 after surgery, corneal epithelium defect area were (39.31
      +/- 22.77) mm(2), and then decreased to (1.01 +/- 1.72) mm(2) at 7 days (t =
      6.68, 5.55, P < 0.05). At day 7 postoperative, 66.7% patients had a complete
      recovery of corneal epithelium with no fluorescein staining. CONCLUSIONS: FD-OCT
      was the effective instrument for observing the change of limbus-peripheral cornea
      epithelium thickness.Within 7 days postoperatively, cornea epithelium restored
      almost normal. After pterygium surgery, limbus-peripheral cornea epithelium
      restoration showed the tendency from the central to peripheral cornea.

PMID- 25582210
TI  - [Top ten progressions of clinical research in fundus diseases in China].
AB  - Ten research items in the past five years representing the progression of
      clinical research in fundus diseases in China were voted by specialists from the
      Ocular Fundus Disease Group of Ophthalmology Society of Chinese Medical
      Association. Choroidal neovascular disease, pediatric retinal disease, polypoidal
      choroidal vasculopathy, intraocular malignant tumor, and intraocular infection
      caused by specific pathogens are covered. Novel treatment, like anti-VEGF
      medication, PDT, minimally invasive vitrectomy, and intraocular injection,
      establishment of the Clinical Research Center of New Drug Development, and the
      epidemiologic study of fundus diseases are also included. These landmark research
      progressions represent the power and influence of Chinese fundus disease scholars
      in the world. 

PMID- 25582211
TI  - [Research update of ocriplasmin for symptomatic vitreomacular adhesion].
AB  - Ocriplasmin is a recombinant truncated form of human serine protease plasmin with
      proteolytic activity to induce vitreous liquefaction and weaken vitreomacular
      adhesion, thereby facilitating posterior vitreous detachment and acting as a
      potential alternative to replace the more traumatic vitrectomy which can result
      in incomplete vitreoretinal separation. Intravitreal ocriplasmin for symptomatic
      vitreomacular adhesion has been systematically evaluated in clinical trials.
      Ocriplasmin at the recommended dose of a single 125 ug intravitreal injection has
      recently been approved for the treatment of symptomatic VMA in the USA and EU.
      This review is aiming to highlight the research update of ocriplasmin. 

PMID- 25582212
TI  - [Research progress of anti-angiogenesis drug targets in diabetic retinopathy].
AB  - Diabetic retinopathy is one of the common ocular diseases. One of the
      pathological characteristic of proliferative diabetic retinopathy is retinal
      neovascularization which caused visual impairment in diabetic patients. With the
      anti-VEGF drugs applying in the clinic, it has become one of the main medical
      treatment of diabetic retinopathy. But it has its limitation. Researchers
      continue to explore new drug targeting for anti-angiogenesis and try combination
      therapy or customized treatment. There are many drug targets for anti
      angiogenesis, such as promoting angiogenesis factor, integrins and matrix
      proteinases. Some drugs act on the typical tip cells which is much important in
      the process of angiogenesis differentiation and proliferation. Overall, these
      studies opened our view of anti-angiogenesis. The purpose of this article is to
      summarize the possible drug targets of angiogenesis and the key issues in the
      study of anti-angiogenic drugs. 

PMID- 25582213
TI  - Therapeutic interference with leukocyte recirculation in multiple sclerosis.
AB  - Multiple sclerosis (MS) is an immune-mediated disease where T cells are thought
      to initiate an inflammatory reaction in the brain and spinal cord, resulting in
      demyelination and axonal pathology. Interfering with the activation and
      recruitment of immune cells reduces disease activity in MS. We review the
      mechanism of action and treatment effects of natalizumab and fingolimod, which
      interfere with the recruitment of pathogenic immune cells in MS. Fingolimod
      blocks the egress of activated lymphocytes from lymph nodes by binding to the
      sphingosine-1-phosphate (S1P) receptor 1, but may also have effects on S1P
      receptor-expressing cells within the central nervous system (CNS). Natalizumab
      reduces the migration of lymphocytes to the CNS by binding to the alpha4 integrin
      very late antigen 4. Fingolimod and natalizumab also have other effects, but
      these are less well understood. Both treatments are efficacious in reducing
      relapses, accumulation of persisting disability and magnetic resonance imaging
      disease activity. Both treatments are safe and well tolerated in the majority of
      patients, but due to a potential for serious side effects they are licensed as
      second line therapies or for treatment of highly active MS in most European
      countries. We conclude that fingolimod and natalizumab have well known effects on
      the migration of immune cells in MS and have substantial effects on disease
      activity in relapsing-remitting MS. Additional effects on disease progression,
      potential effects within the CNS and other effects on immune cells are still
      being clarified. 

PMID- 25582214
TI  - Validation of balance-quality assessment using a modified bathroom scale.
AB  - The balance quality tester (BQT), based on a standard electronic bathroom scale
      has been developed in order to assess balance quality. The BQT includes automatic
      detection of the person to be tested by means of an infrared detector and
      bluetooth communication capability for remote assessment when linked to a long
      distance communication device such as a mobile phone. The BQT was compared to a
      standard force plate for validity and agreement. The two most widely reported
      parameters in balance literature, the area of the centre of pressure (COP)
      displacement and the velocity of the COP displacement, were compared for 12
      subjects, each of whom was tested on ten occasions on each of the 2 days. No
      significant differences were observed between the BQT and the force plate for
      either of the two parameters. In addition a high level of agreement was observed
      between both devices. The BQT is a valid device for remote assessment of balance
      quality, and could provide a useful tool for long-term monitoring of people with
      balance problems, particularly during home monitoring.

PMID- 25582215
TI  - In-transit metastatic melanoma involving a previously fractured patella.

PMID- 25582216
TI  - Identification of the novel KIR2DL2*013 allele from a southern Chinese Han
      individual.
AB  - The novel KIR2DL2*013 allele differs from the closest allele KIR2DL2*00302 by two
      non-synonymous mutations. 

PMID- 25582218
TI  - A 24-chromosome FISH technique in preimplantation genetic diagnosis: validation
      of the method.
AB  - Embryo screening for aneuploidy (AS) is part of preimplantation genetic
      diagnostics (PGD) and is aimed at improving the efficiency of assisted
      reproduction. Currently, several technologies, including the well-established
      fluorescence in situ hybridization (FISH) technique, cover the screening of all
      chromosomes in a single cell. This study evaluates a novel 24-chromosome FISH
      technique protocol (FISH-24). A total of 337 embryos were analyzed using the
      traditional 9-chromosome FISH technique (FISH-9) while 251 embryos were evaluated
      using the new FISH-24 technique. Embryos deemed nontransferable on Day 3 were
      cultured in vitro to Day 5 of development, then fixed and reanalyzed according to
      the technique allocated to each treatment cycle (107 embryos analyzed by FISH-9
      and 111 by FISH-24). The global error rate (discrepancy between Day 3 and Day 5
      results for a single embryo) was 2.8% after FISH-9 and 3.6% after FISH-24, with a
      p value of 0.95. Thus, we have established and validated a 24-chromosome FISH
      based single cell aneuploidy screening technique, showing that the error rate
      obtained for FISH-24 is independent of the number of chromosomes analyzed and
      equivalent to the error rate observed for FISH-9, as a useful tool for chromosome
      segregation studies and clinical use. 

PMID- 25582217
TI  - Radiation therapy at the end of life: a population-based study examining
      palliative treatment intensity.
AB  - BACKGROUND: To examine factors associated with the use of radiation therapy (RT)
      at the end of life in patients with breast, prostate, or colorectal cancer.
      METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) -
      Medicare database, patients were over age 65 and diagnosed between January 1,
      2004 and December 31, 2011 with any stage of cancer when the cause of death, as
      defined by SEER, was cancer; or with stage 4 cancer, who died of any cause. We
      employed multiple logistic regression models to identify patient and health
      systems factors associated with palliative radiation use. RESULTS: 50% of
      patients received RT in the last 6 months of life. RT was used less frequently in
      older patients and in non-Hispanic white patients. Similar patterns were observed
      in the last 14 days of life. Chemotherapy use in the last 6 months of life was
      strongly correlated with receiving RT in the last 6 months (OR 2.72, 95% CI: 2.59
      2.88) and last 14 days of life (OR 1.55, 95% CI: 1.40-1.66). Patients receiving
      RT accrued more emergency department visits, radiographic exams and physician
      visits (all comparisons p < 0.0001). CONCLUSIONS: Among patients with breast,
      colorectal, and prostate cancer, palliative RT use was common. End-of-life RT
      correlated with end-of-life chemotherapy use, including in the last 14 days of
      life, when treatment may cause increased treatment burden without improved
      quality of life. Research is needed optimize the role and timing of RT in
      palliative care.

PMID- 25582220
TI  - Simple screening strategy with only water bath needed for the identification of
      insect-resistant genetically modified rice.
AB  - An informative, with simple instrument needed, rapid and easily updated strategy
      for the identification of insect-resistant genetically modified (GM) rice has
      been described. Such strategy is based on a parallel series of loop-mediated
      isothermal amplification (LAMP) reactions targeting the rice endogenous gene
      sucrose phosphate synthase (Sps), the top two most frequently used genetic
      elements (Agrobacterium tumefaciens nopaline synthase terminator (Nos) and
      Cauliflower mosaic virus 35S promoter (CaMV35S)), and an insect-resistant
      specific gene (Cry1Ac) and detected visually by phosphate ion (Pi)-induced
      coloration reaction. After a logical judgment of visible readouts has been
      obtained, three popular insect-resistant GM rice events in China can be
      successfully identified within 35 min, using either microwell strips or paper
      bases. 

PMID- 25582219
TI  - Screening blood-fed mosquitoes for the diagnosis of filarioid helminths and avian
      malaria.
AB  - BACKGROUND: Both Dirofilaria repens and recently D. immitis are known to be
      endemic in Hungary. As one of several recent cases, the fatal case of a dog
      infested with D. immitis in Szeged, Southern Hungary, received attention from the
      media. Hence it was decided to catch mosquitoes in the garden where the dog lived
      to screen for filarioid helminths and Plasmodium spp. using molecular tools.
      METHODS: Mosquitoes were caught in Szeged, in the garden where the infected dog
      was kept, in July 2013 with M-360 electric mosquito traps and were stored in
      ethanol until further procedure. Female mosquitoes were classified to genus level
      by morphology. Each mosquito was homogenized and analyzed for filarioid helminths
      and avian malaria using standardized PCR techniques. Positive mosquito samples
      were further identified to species level by comparing a section of the
      mitochondrial COI gene to GenBank(r) entries. RESULTS: In this study, 267 blood
      fed mosquitoes were caught in July 2013 in Szeged. Subsequent molecular screening
      revealed that not only D. immitis was present in the analyzed specimens but also
      DNA of D. repens, Setaria tundra and Plasmodium spp. was confirmed. CONCLUSIONS:
      The analysis of blood-fed mosquitoes for the diagnosis of Dirofilaria spp. and
      other mosquito-borne pathogens seems to be an adequate technique to evaluate if
      filarioid helminths are present in a certain area. Usually only unfed female
      mosquitoes are analyzed for epidemiological studies. However, blood-fed
      mosquitoes can only be used for screening if a pathogen is present because the
      role of the mosquito as vector cannot be classified (blood of bitten host).
      Furthermore, Setaria tundra was confirmed for the first time in Hungary.

PMID- 25582221
TI  - A novel software program for detection of potential air emboli during cardiac
      surgery.
AB  - BACKGROUND: Risks associated with air emboli introduced during cardiac surgery
      have been highlighted by reports of postoperative neuropsychological dysfunction,
      myocardial dysfunction, and mortality. Presently, there are no standard effective
      methods for quantifying potential emboli in the bloodstream during cardiac
      surgery. Our objective was to develop software that can automatically detect and
      quantify air bubbles within the ascending aorta and/or cardiac chambers during
      cardiac surgery in real time. FINDINGS: We created a software algorithm
      ("Detection of Emboli using Transesophageal Echocardiography for Counting, Total
      volume, and Size estimation", or DETECTSTM) to identify and measure potential
      emboli present during cardiac surgery using two-dimensional ultrasound. An in
      vitro experiment was used to validate the accuracy of DETECTSTM at identifying
      and measuring air emboli. An experimental rig was built to correlate the
      ultrasound images to high definition camera images of air bubbles created in
      water by an automatic bubbler system. There was a correlation between true bubble
      size and the size reported by DETECTSTM in our in vitro experiment (r = 0.76). We
      also tested DETECTSTM using TEE images obtained during cardiac surgery, and
      provide visualization of the software interface. CONCLUSIONS: While monitoring
      the heart during cardiac surgery using existing ultrasound technology and
      DETECTSTM, the operative team can obtain real-time data on the number and volume
      of potential air emboli. This system will potentially allow de-airing techniques
      to be evaluated and improved upon. This could lead to reduced air in the cardiac
      chambers after cardiopulmonary bypass, possibly reducing the risk of neurological
      dysfunction following cardiac surgery.

PMID- 25582222
TI  - A therapy-grade protocol for differentiation of pluripotent stem cells into
      mesenchymal stem cells using platelet lysate as supplement.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) are a promising source of cells for
      regenerative therapies. Although they can be isolated easily from several
      tissues, cell expansion is limited since their properties are lost with
      successive passages. Hence, pluripotent derived MSCs (PD-MSCs) arise as a
      suitable alternative for MSC production. Nevertheless, at present, PD-MSC
      derivation protocols are either expensive or not suitable for clinical purposes.
      METHODS: In this work we present a therapy-grade, inexpensive and simple protocol
      to derive MSCs from pluripotent stem cells (PSCs) based on the use of platelet
      lysate (PL) as medium supplement. RESULTS: We showed that the PD-MSCPL expressed
      multiple MSC markers, including CD90, CD73, CD105, CD166, and CD271, among
      others. These cells also show multilineage differentiation ability and
      immunomodulatory effects on pre-stimulated lymphocytes. Thorough characterization
      of these cells showed that a PD-MSCPL resembles an umbilical cord (UC) MSC and
      differs from a PSC in surface marker and extracellular matrix proteins and
      integrin expression. Moreover, the OCT-4 promoter is re-methylated with
      mesenchymal differentiation comparable with the methylation levels of UC-MSCs and
      fibroblasts. Lastly, the use of PL-supplemented medium generates significantly
      more MSCs than the use of fetal bovine serum. CONCLUSIONS: This protocol can be
      used to generate a large amount of PD-MSCs with low cost and is compatible with
      clinical therapies.

PMID- 25582224
TI  - Gestational age and learning disabilities.

PMID- 25582223
TI  - Helicobacter Pylori Infection is Positively Associated with Metabolic Syndrome in
      Taiwanese Adults: a Cross-Sectional Study.
AB  - BACKGROUND: Helicobacter pylori infection and metabolic syndrome have been
      reported to be positively associated. However, only a few studies have focused on
      this issue, and H. pylori serum antigen was used to diagnose infection in most of
      them. We aimed to investigate the association between metabolic syndrome factors
      and H. pylori infection, as diagnosed via a (13)C-urea breath test. MATERIALS AND
      METHODS: This cross-sectional study consisted of 3578 subjects (18-64 years old)
      enrolled from one health management center between 2008 and 2013. H. pylori
      infection was defined as a positive urea breath test. The risk of metabolic
      syndrome from H. pylori infection was assessed using a multiple logistic
      regression model. RESULTS: The prevalence of the H. pylori was similar in both
      genders (20.6% in men and 19.7% in women). H. pylori -infected participants had
      significantly higher body mass index, fasting glucose, low-density lipoprotein,
      and triglycerides, and lower high-density lipoprotein (p < 0.05), than uninfected
      ones (p < 0.05). The prevalence of metabolic syndrome was higher in H. pylori 
      infected subjects than uninfected ones (men: 12.4% vs. 7.4%, p < 0.001; women:
      7.4% vs. 2.5%, p < 0.001). Furthermore, H. pylori infection prevalence increased
      with metabolic score (P for trend <0.001, both sexes). Moreover, the association
      between metabolic syndrome and UBT positivity was significant in females (OR
      1.91, 95% CI:1.03-3.53), but only borderline significant in males (OR 1.38, 95%
      CI: 0.97-1.95). CONCLUSION: H. pylori infection is positively associated with
      metabolic syndrome, especially in females. The causal relationship between H.
      pylori infection and metabolic syndrome warrants further investigation.

PMID- 25582225
TI  - Identifying a gene expression signature of frequent COPD exacerbations in
      peripheral blood using network methods.
AB  - BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD),
      characterized by acute deterioration in symptoms, may be due to bacterial or
      viral infections, environmental exposures, or unknown factors. Exacerbation
      frequency may be a stable trait in COPD patients, which could imply genetic
      susceptibility. Observing the genes, networks, and pathways that are up- and down
      regulated in COPD patients with differing susceptibility to exacerbations will
      help to elucidate the molecular signature and pathogenesis of COPD exacerbations.
      METHODS: Gene expression array and plasma biomarker data were obtained using
      whole-blood samples from subjects enrolled in the Treatment of Emphysema With a
      Gamma-Selective Retinoid Agonist (TESRA) study. Linear regression, weighted gene
      co-expression network analysis (WGCNA), and pathway analysis were used to
      identify signatures and network sub-modules associated with the number of
      exacerbations within the previous year; other COPD-related phenotypes were also
      investigated. RESULTS: Individual genes were not found to be significantly
      associated with the number of exacerbations. However using network methods, a
      statistically significant gene module was identified, along with other modules
      showing moderate association. A diverse signature was observed across these
      modules using pathway analysis, marked by differences in B cell and NK cell
      activity, as well as cellular markers of viral infection. Within two modules,
      gene set enrichment analysis recapitulated the molecular signatures of two gene
      expression experiments; one involving sputum from asthma exacerbations and
      another involving viral lung infections. The plasma biomarker myeloperoxidase
      (MPO) was associated with the number of recent exacerbations. CONCLUSION: A
      distinct signature of COPD exacerbations may be observed in peripheral blood
      months following the acute illness. While not predictive in this cross-sectional
      analysis, these results will be useful in uncovering the molecular pathogenesis
      of COPD exacerbations.

PMID- 25582226
TI  - ABT-450: a novel agent for the treatment of CHC genotype 1: focus on treatment
      experienced patients.
AB  - Chronic hepatitis C (CHC) constitutes a major health concern. Hepatitis C virus
      eradication by antiviral treatment can markedly reduce the risk of developing
      cirrhosis, hepatocellular carcinoma and liver-related death. A plethora of new
      direct antiviral agents have been developed and are being explored in clinical
      trials. One of the newest members of this family is the NS3/4A protease inhibitor
      ABT-450. The multi-targeted approach combining ritonavir-enhanced ABT-450 with
      ombitasvir and dasabuvir has been evaluated for the treatment of CHC Gt1 in
      treatment-naive and treatment-experienced adults. In this article, we sought to
      discuss the current knowledge on ABT-450-containing regimens, with special
      emphasis on treatment-experienced CHC Gt1 patients. This new combination was
      found to be potent, safe and well tolerated. Future Phase III trials with larger
      sample size in patients with decompensated cirrhosis, non-Gt1, end-stage renal
      disease and liver transplant recipients are eagerly awaited. 

PMID- 25582228
TI  - Erratum.

PMID- 25582227
TI  - Prevalence of depression, fatigue, and sleep disturbances in patients with
      myelopathy: Their relation with functional and neurological recovery.
AB  - OBJECTIVES: To observe the prevalence of fatigue, depression, and sleep
      disturbance in patients with myelopathy and their correlation with neurological
      and functional recovery. PATIENTS AND METHODS: Study conducted in a university
      tertiary research hospital with 127 patients with myelopathy (92 males) admitted
      to neurorehabilitation unit between January 2010 and December 2013. Mean age was
      32.71 +/- 13.08 years (range 15-65 years), and mean duration of injury was 76.22
      +/- 82.5 days (range 14-365 days). Functional status and impairments were
      assessed using Barthel Index and Spinal Cord Independence Measures. Depression,
      fatigue, and sleep disturbances were assessed using Hospital Anxiety and
      Depression Scale, Fatigue Severity Scale, and Pittsburgh Sleep Quality Index
      scales, respectively. Neurological recovery was assessed using American Spinal
      Injury Association's impairment scale. RESULTS: Forty-four out of 104 (42%)
      patients had borderline or confirmed depression, 36/108 (33%) had significant
      fatigue, and 62/106 (58%) had significant sleep disturbances at admission.
      Significant correlation was observed between change in fatigue and depression
      scores with change in functional status scores (P < 0.05) but no correlation (P >
      0.05) between change in sleep disturbance scores and functional status score and
      neurological recovery (P > 0.05). Similarly, change in fatigue and depression
      scores had no correlation with neurological status improvement. Fatigue,
      depression, and sleep disturbance scores showed significant improvement, that is,
      admission vs. discharge scores (P < 0.05) with significant correlation between
      improvement in all three variables (P < 0.05). CONCLUSIONS: Study variables
      showed significant improvement in the present study with myelopathy patients but
      not necessarily correlating with functional and neurological recovery.

PMID- 25582229
TI  - The association between metal allergy, total knee arthroplasty, and revision:
      study based on the Danish Knee Arthroplasty Register.
AB  - BACKGROUND AND PURPOSE: It is unclear whether delayed-type hypersensitivity
      reactions against implanted metals play a role in the etiopathogenesis of
      malfunctioning total knee arthroplasties. We therefore evaluated the association
      between metal allergy, defined as a positive patch test reaction to common metal
      allergens, and revision surgery in patients who underwent knee arthroplasty.
      PATIENTS AND METHODS: The nationwide Danish Knee Arthroplasty Register, including
      all knee-implanted patients and revisions in Denmark after 1997 (n = 46,407), was
      crosslinked with a contact allergy patch test database from the greater
      Copenhagen area (n = 27,020). RESULTS: 327 patients were registered in both
      databases. The prevalence of contact allergy to nickel, chromium, and cobalt was
      comparable in patients with and without revision surgery. However, in patients
      with 2 or more episodes of revision surgery, the prevalence of cobalt and
      chromium allergy was markedly higher. Metal allergy that was diagnosed before
      implant surgery appeared not to increase the risk of implant failure and revision
      surgery. INTERPRETATION: While we could not confirm that a positive patch test
      reaction to common metals is associated with complications and revision surgery
      after knee arthroplasty, metal allergy may be a contributor to the multifactorial
      pathogenesis of implant failure in some cases. In cases with multiple revisions,
      cobalt and chromium allergies appear to be more frequent.

PMID- 25582231
TI  - Mental health among living kidney donors: a prospective comparison with matched
      controls from the general population.
AB  - The impact of living kidney donation on donors' mental health has not been
      sufficiently nor comprehensively studied. Earlier studies demonstrated that
      mental health did not change in the majority of donors, however they often lacked
      a suitable control group and/or had other methodological limitations.
      Consequently, it remains unclear whether changes in mental health found among a
      minority of donors reflect normal fluctuations. In this study we matched 135
      donors with individuals from the general Dutch population on gender and baseline
      mental health and compared changes in mental health over time. Mental health was
      measured using the Brief Symptom Inventory and Mental Health Continuum Short
      Form. Primary analyses compared baseline and 6 months follow-up. Secondary
      analyses compared baseline and 9 (controls) or 15 months (donors) follow-up.
      Primary multilevel regression analyses showed that there was no change in
      psychological complaints (p = 0.20) and wellbeing (p = 0.10) over time and donors
      and controls did not differ from one another in changes in psychological
      complaints (p = 0.48) and wellbeing (p = 0.85). Secondary analyses also revealed
      no difference in changes between the groups. We concluded that changes in mental
      health in the short term after donation do not significantly differ from normal
      fluctuations found in the Dutch general population.

PMID- 25582233
TI  - TRANSFUSION enhancements in the digital age.

PMID- 25582232
TI  - LACK, a RACK1 ortholog, facilitates cytochrome c oxidase subunit expression to
      promote Leishmania major fitness.
AB  - Leishmania are kinetoplastid parasites that cause the sandfly-transmitted disease
      leishmaniasis. To maintain fitness throughout their infectious life cycle,
      Leishmania must undergo rapid metabolic adaptations to the dramatically distinct
      environments encountered during transition between sandfly and vertebrate hosts.
      We performed proteomic and immunoblot analyses of attenuated L. major strains
      deficient for LACK, the Leishmania ortholog of the mammalian receptor for
      activated c kinase (RACK1), that is important for parasite thermotolerance and
      virulence. This approach identified cytochrome c oxidase (LmCOX) subunit IV as a
      LACK-dependent fitness protein. Consistent with decreased levels of LmCOX subunit
      IV at mammalian temperature, and in amastigotes, LmCOX activity and mitochondrial
      function were also impaired in LACK-deficient L. major under these conditions.
      Importantly, overexpression of LmCOX subunit IV in LACK-deficient L. major
      restored thermotolerance and macrophage infectivity. Interestingly,
      overexpression of LmCOX subunit IV enhanced LmCOX subunit VI expression at
      mammalian temperature. Collectively, our data suggest LACK promotes Leishmania
      adaptation to the mammalian host environment by sustaining LmCOX subunit IV
      expression and hence energy metabolism in response to stress stimuli such as
      heat. These findings extend the repertoire of RACK1 protein utility to include a
      role in mitochondrial function. 

PMID- 25582235
TI  - Plasma transfusion trials and tribulations.

PMID- 25582234
TI  - Measuring ADAMTS13 activity in patients with suspected thrombotic
      thrombocytopenic purpura: when, how, and why?

PMID- 25582236
TI  - Transfusion Medicine History Illustrated. Norman Bethune and the mobile
      transfusion service.

PMID- 25582238
TI  - The future of red blood cell alloimmunization risk reduction.

PMID- 25582239
TI  - Prospective antigen matching strategies fail to fit the model.

PMID- 25582240
TI  - The future of red blood cell alloimmunization risk reduction.

PMID- 25582241
TI  - Reflections on the emergence of chikungunya virus in the United States: time to
      revisit a successful paradigm for the safety of blood-derived therapies.

PMID- 25582242
TI  - Immunosuppressive medication and alloimmunization to red blood cell antigens.

PMID- 25582243
TI  - A successful child-to-adult deceased donor liver transplantation: a case report
      and literature review.
AB  - BACKGROUND: Size mismatch, which might result in small-for-size syndrome, is
      still a major limitation of liver transplantation. Prior data has suggested that
      a graft-to-recipient weight ratio <0.8% was a risk factor for developing small
      for-size syndrome. CASE REPORT: We report the case of a 60-year-old woman who
      received a whole liver graft, with an estimated graft-to-recipient weight ratio
      of 0.46%, from a 10-year-old child donor weighing 12.8 kg pre-operatively.
      Delicate graft inflow modulation was performed according to the intra-operative
      hemodynamic changes, including portal vein flow, hepatic artery flow, portal vein
      pressure, and hepatic venous pressure gradient, to avoid small-for-size syndrome.
      CONCLUSIONS: The post-transplant course was uneventful and satisfactory. To the
      best of our knowledge, this is the first reported case of a successful adult
      deceased donor liver transplantation using a whole liver graft from a brain-dead
      pediatric donor.

PMID- 25582244
TI  - Efficacy of hepatic T2* MRI values and serum ferritin concentration in predicting
      thalassemia major classification for hematopoietic stem cell transplantation.
AB  - Liver biopsy has been performed for many decades for classifying the patients
      with TM. Meanwhile, using non-invasive methods such as T2* MRI technique has been
      recently much more considered to determine the hepatic iron overload. Ninety
      three pediatric HSCT candidates with TM who underwent liver biopsy were included
      in this study. Hepatic T2* MRI values and serum ferritin concentrations were
      assessed to investigate and determine the useful method in detection of patients
      with TM class III whom received different conditioning regimens, in comparison
      with class I and II. Twenty (21.5%) patients were categorized as class III.
      Hepatic T2* MRI could detect TM class III patients with 60% sensitivity and
      87.67% specificity (LR+: 4.867, accuracy: 81.72%), while predictive feature of
      ferritin values for distinguishing patients with TM class III was not
      statistically significant (p-value >0.01). Combination of T2*MRI with age (T2*
      age) could detect TM class III with 85% sensitivity and 72.6% specificity (LR+:
      3.1, accuracy: 75.27%).T2*-age may be considered as an alternative and non
      invasive method to liver biopsy for differentiation and classification of
      patients with TM before transplantation. 

PMID- 25582245
TI  - Antimicrobial use in critically ill horses.
AB  - OBJECTIVE: To discuss controversies surrounding antimicrobial use in critically
      ill horses. DATA SOURCES: PubMed searches from 1970-present for terms including,
      but not limited to: "horse," "foal," "antimicrobial," "prophylaxis," "infection,"
      "surgery," "sepsis," and "antimicrobial resistance." HUMAN DATA SYNTHESIS:
      Increasing bacterial antimicrobial resistance has changed first-line
      antimicrobial choices and prompted shortening of the duration of prophylactic and
      therapeutic treatment. The need to decrease bacterial resistance development to
      critically important antimicrobials has been highlighted. VETERINARY DATA
      SYNTHESIS: Veterinary medicine has followed a similar trend but often without a
      high-level evidence. Common dilemmas include diseases in which the theoretically
      most effective drug is a reserved antimicrobial, the inability to differentiate
      infectious from noninfectious disease, the duration and necessity of prophylactic
      antimicrobials and use of antimicrobials in primary gastrointestinal disease.
      These problems are illustrated using examples of purulent infections, neonatal
      sepsis, colic surgery, and treatment of colitis. Although enrofloxacin,
      cephalosporins, and doxycycline, in contrast to gentamicin, reach therapeutic
      concentrations within the lungs of healthy horses, the first two should not be
      used as first line treatment due to their reserved status. Due to the high risk
      of bacterial sepsis, antimicrobial treatment remains indispensable in compromised
      neonatal foals but shortening the length of antimicrobial treatment might be
      prudent. One prospective randomized study demonstrated no difference between 3
      and 5 days of perioperative antimicrobial treatment in colic surgery but shorter
      durations were not evaluated. High-level evidence to recommend antimicrobial
      treatment of adult horses with undifferentiated diarrhea does not exist.
      CONCLUSIONS: Few evidence-based recommendations can be made. Commonly used
      antimicrobial combinations remain the mainstay for treating purulent infections.
      Antimicrobial treatment for compromised foals should not extend beyond recovery.
      Continuation of prophylactic antimicrobials >3 days is likely unnecessary after
      colic surgery; shorter durations might be equally effective. Antimicrobial
      prophylaxis in adult horses with diarrhea is unlikely to be beneficial.

PMID- 25582247
TI  - [Multilocular cystic clear cell neoplasm of low malignant potential: evolving
      concept, classification and unifying terminology].

PMID- 25582246
TI  - Role of subchondral bone remodelling in collapse of the articular surface of
      Thoroughbred racehorses with palmar osteochondral disease.
AB  - REASONS FOR PERFORMING STUDY: To gain a better understanding of the aetiology of
      articular surface collapse in horses with palmar osteochondral disease.
      OBJECTIVES: To determine whether acceleration of focal bone resorption associated
      with reduced physical activity contributes to articular surface collapse in
      racehorses with palmar osteochondral disease. STUDY DESIGN: Cross-sectional study
      comparing metacarpal bones from horses at varying stages of race training.
      METHODS: Metacarpal bones from 36 racing Thoroughbred horses were examined with
      high-resolution peripheral quantitative computed tomography to determine the
      proportion of the articular surface that had collapsed and with backscattered
      scanning electron microscopy to quantify porosity and eroded bone surface. Racing
      and training histories were obtained for comparison with imaging data. RESULTS:
      In 21 cases, inward collapse of the calcified cartilage layer was observed on
      backscattered scanning electron microscopy. An increased extent of articular
      surface collapse was associated with greater numbers of microfractures in the
      calcified cartilage and superficial subchondral bone (Spearman's correlation [rs
      ] = 0.62, P<0.001). In the deeper bone (6-10 mm), porosity was lower with a
      greater extent of articular surface collapse (rs = -0.38, P = 0.023), whereas in
      the superficial bone (0-4 mm) there was no association between articular surface
      collapse and porosity (rs = 0.19, P = 0.26). Both porosity (median 14, range 3.8
      26 vs. 3.8, 1.6-17%, P = 0.008) and eroded surface (1.1, 0.74-4.5 vs. 0.64, 0.11
      4.7 mm(-1) , P = 0.016) of the superficial subchondral bone were higher in
      resting than in training horses, and in some resting horses subchondral bone
      voids were highly concentrated, resulting in an apparent loss of support for the
      overlying calcified cartilage layer. CONCLUSIONS: Articular surface collapse is
      common in cases of palmar osteochondral disease and is likely to be a sequel to
      fatigue injury of subchondral bone. Focal subchondral bone resorption appears to
      contribute to collapse of the calcified cartilage and is potentiated by a reduced
      intensity exercise regimen.

PMID- 25582248
TI  - [Clinicopathologic features and differential diagnosis of multilocular cystic
      renal cell carcinoma].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics and the
      diagnosis of multilocular cystic renal cell carcinoma (MCRCC). METHODS: The
      clinicopathological data of 19 MCRCC cases were collected and immunohistochemical
      staining assays were carried out. Forty-six cases of other cystic kidney lesions
      within the same period were collected as controls, including extensively cystic
      clear cell RCC (12 cases), clear cell tubulopapillary renal cell carcinoma (6
      cases), tubulocystic carcinoma (2 cases), simple cortical cysts (22 cases),
      multilocular cystic nephroma (1 cases) and multicystic kidney (3 cases). RESULTS:
      The patients included 14 males and 5 females. The ages ranged from 31 to 66 years
      (median age = 50 years). Most of the MCRCC cases were detected incidentally in
      physical examination, occasionally accompanied with hematuria, back pain or other
      symptoms. The follow-up period of 17 patients ranged from 6 to 170 months. All
      patients were alive without evidence of tumor recurrence or metastasis.
      Pathological findings showed that macroscopically, tumor size ranges from 1.5 to
      7.0 cm in the maximum diameter, generally a entirely of various sized. The cysts
      contain serous, hemorrhagic or turbid fluid. Solid areas or substantially
      discernible mural nodules were absent; histologicallly, single layer of cuboidal
      and flattened epithelial tumor cells were lined in the cysts, described as clear
      cytoplasm, small nuclear, no nucleoli and low Fuhrman nuclear grade (I or II).
      Multilayer tumor cells could be observed in a few cysts, with granular cytoplasm
      and small intracystic papillae formed. The clear tumor cell clusters, similar as
      cystic lined tumor cells, were seen within pathological fibrous in almost all
      cases, and significant myofibroblastic proliferation was found in 14 cases.
      Immunohistochemically, the cysts lined epithelial cells and the clear tumor cell
      clusters were positive for epithelium markers, including CKpan(19/19), EMA(16/19)
      and CK7 (15/19); higher percentage of CAIX (17/19) and PAX8(15/19) than control
      groups, but lower percentage of CD10 (7/19), RCC (6/19) and AMACR(2/19); and all
      were negative for 34betaE12, CD117 and CD68. CONCLUSIONS: Multilocular cysts,
      clear cells clusters of low Fuhrman grade within fibrous septa and capillary
      vessel proliferation under epithelium are important features of MCRCC. The united
      using of CAIX, CK7, CD10 and RCC is helpful for differentiating variable cystic
      renal tumor. MCRCC usually has an excellent prognosis, nephron sparing surgery is
      first recommended as a therapeutic strategy.

PMID- 25582249
TI  - [Clinicopathologic features of clear cell papillary renal cell carcinoma].
AB  - OBJECTIVE: To study the clinicopathological features, differential diagnosis and
      prognosis of clear cell papillary renal cell carcinoma (CCPRCC). METHODS: The
      histological, immunohistochemical, and molecular features were studied in 11
      cases and follow-up data were also analyzed. RESULTS: There were a total of 3
      females and 8 males. The age of patients were ranged from 33 to 72 years(mean age
      52.5 years). The diameters of tumors varied from 1cm to 4 cm. Histologically,
      papillary and cystic architecture were present at least focally in all tumors.
      The papillae were covered by small to medium-sized cuboidal cells with abundant
      clear cytoplasm and often showed extensive secondary branching, which were often
      folded and densely packed, resulting in a solid appearance. The nuclei were round
      and uniform in shape; nucleoli were not prominent (Fuhrman grade 1 or 2). Neither
      mitotic figures nor necrosis was present. All 11 cases exhibited moderate to
      strong positivity for CK7, CA9, vimentin, and HIF-1alpha, coupled with negative
      reactions for CD10, P504S, and TFE3. Ksp-cadherin was positively expressed in 8
      cases.VHL gene mutations were not found in all 11 cases. Losses of chromosomes 3
      (monoploid chromosome 3) was detected in 3 cases. CONCLUSIONS: CCPRCC is uncommon
      and seemed to be an indolent tumor. The differential diagnosis should be included
      tumors, which harbor clear cell and papillary structure including clear cell
      renal cell carcinoma, papillary renal cell carcinoma, Xp11 translocation renal
      cell carcinoma, and CCPRCC. Immunohistochemical and molecular analysis may be
      help for its diagnosis.

PMID- 25582250
TI  - [Clinicopathologic features of collagen III glomerulopathy].
AB  - OBJECTIVE: To study the clinicopathologic features of collagen III glomerulopathy
      and its cause, pathogenesis and prognosis. METHODS: Five cases of collagen III
      glomerulopathy that collected from 2005 to 2014 were observed by renal biopsy.
      The morphologic characteristics were studied by light microscopy,
      immunofluorescence, immunohistochemical and electron microscopy. RESULTS: The
      glomerular mesangium became expansion but no hypercellularity, basement membrane
      appeared thickened. The glomeruli showed collagen type III deposit by
      immunohistochemistry method, and collagen fibers increased by electron
      microscopy. The patients often show serious proteinuria, nephrotic syndrome and
      renal function damage. CONCLUSIONS: Collagen III glomerulopathy is an idiopathic
      glomerular disease, characterized by massive accumulation of collagen type III
      within the glomerular mesangial areas and basement membrane. Collagen III
      glomerulopathy is extremely rare. The etiology and pathogenesis may relate to the
      abnormality of collagen III gene. There is no specific treatment for it and its
      prognosis is poor.

PMID- 25582251
TI  - [Neuroendocrine carcinoma of the urinary bladder:clinicopathologic features
      analysis of 17 cases].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics and the
      prognosis of bladder neuroendocrine carcinoma (NEC). METHODS: Clinicopathological
      data from 17 NEC of the bladder cases were collected, and immunohistochemical
      staining was performed with follow-up analysis and literature review. RESULTS:
      The recruited included 13 male and 4 female patients, aged from 48 to 86 years
      old (average 61 years; 14 patients >60 years). Gross hematuria of the whole
      urination course or intermittent was the initial symptom. Macroscopically, the
      outer surface of the tumor presented with polypoid, lobulated, fungating or
      ulcerous structures. Histologically, according to the criteria of WHO
      classification of neuroendocrine tumor of the lung, our NEC cases were divided
      into three histological types: 13 cases of small cell carcinoma, 3 cases of large
      cell neuroendocrine carcinoma and 1 case of atypical carcinoid. The urothelial
      carcinoma was concurrent with NEC in 6 cases, and adenocarcinoma was concurrent
      with NEC in 2 cases. Most tumor tissue infiltrated to the muscular layer, some
      infiltrated to the outer membrane. Immunohistochemically, the positive expression
      rates of CD56, Syn and CgA were 16/17, 16/17 and 12/17, respectively. The
      epithelial markers, including CK7 and CKpan, were also expressed with positive
      rates of 12/17 and 15/17, respectively. TTF-1 was positively expressed in 11
      cases. The follow-up data were available in 14 cases, of which 9 patients died of
      the tumor 1-34 months after surgery (average, 11 months). Five patients lived
      uneventfully for 1-12 months after surgery. CONCLUSIONS: NEC is a rare malignant
      tumor of the bladder. Immunohistochemical markers such as CD56, Syn, CgA and
      CKpan could be helpful in determining the diagnosis and differential diagnosis of
      the tumor. NEC is a highly invasive malignant tumor with poor prognosis. Based on
      its biological behavior, radical cystectomy is the preferred method of treatment
      for the tumor.

PMID- 25582252
TI  - [Expression of anaplastic lymphoma kinase and its clinical significance in non
      small cell lung cancer].
AB  - OBJECTIVE: To investigate the frequency of anaplastic lymphoma kinase (ALK)
      expression in non-small cell lung cancer (NSCLC) patients and its correlation
      with the clinicopathologic features. METHODS: ALK immunohistochemistry and ALK
      fluorescent in situ hybridization (FISH) were performed on formalin-fixed,
      paraffin-embedded tissue in 100 cases of NSCLCs between 2011 and 2013. Relevant
      clinicopathologic data were collected and correlated with ALK expression.
      RESULTS: All patients with immunohistochemical score of 3 (n = 12) were FISH
      positive and all patients with score of 0 (n = 78) were FISH-negative. Among
      patients with immunohistochemical scores of 1 and 2, 2/3 and 6/7 were FISH
      positive, respectively. The sensitivity and specificity of ALK
      immunohistochemistry with intensity score of 1 or more were 100% and 98%,
      respectively. Invasive mucinous adenocarcinoma, solid or acinar growth pattern,
      presence of mucous cells (signet-ring cells or goblet cells), extracellular mucus
      and lack of significant nuclear pleomorphism characterized ALK-rearranged cancer.
      CONCLUSIONS: ALK-rearranged cancers possess specific histological features.
      Immunohistochemistry can be used as a routine test for screening ALK-positive
      cases in advanced NSCLC, and FISH testing should be used to confirm ALK
      translocation for patients with tumors showing staining for ALK by
      immunohistochemistry. All of these can help physicians identify patients who may
      benefit from targeted therapy.

PMID- 25582253
TI  - [Childhood pleuropulmonary blastoma: a clinicopathologic study of 16 cases].
AB  - OBJECTIVE: To study the clinicopathological and immunohistochemical features,
      histogenesis and prognosis of pleuropulmonary blastoma (PPB) in children.
      METHODS: PPB specimens from 16 pediatric cases with an age ranging from 1 year
      and 7 months to 5 years and 3 months (mean age of 3 years) were retrieved and
      analyzed by routine histological, immunohistochemical and electron methods.
      RESULTS: Among 16 patients, there were 2 type I, 7 type II and 7 type III PPB
      cases. Type I PPB as multilocular cystic structure, consisted of thin fibrous
      wall lining the respiratory epithelium, subepithelial primitive blastema or
      immature mesenchymal cells, with or without rhabdomyoblastic differentiation or
      cartilage; Type II PPB as cystic-solid tumor, comparing with type I, consisted of
      intracystic components with appearance of anaplastic tumor cells. Type III PPB
      consisted of completely solid mass, the same as the solid region of type II, had
      mixed pattern including blastema, undifferentiated spindle-cell proliferations
      and sarcomas. In addition, anaplastic tumor cells and intra-and extra-
      cytoplasmic eosinophilic globules were also commonly present. Epithelial
      components in PPB were benign. Immunohistochemical study showed primitive
      mesenchymal differentiation of tumors. All cases were positive for vimentin,
      desmin, myogenin and SMA in tumors with skeletal muscle differentiation, S-100
      was positive in tumors with cartilage differentiation. All tumors were negative
      for synaptophysin, CD99, and CD117. Benign epithelial components were positive
      for AE1/AE3 and EMA. In 12 cases, electron microscopy revealed few organelles in
      the primitive mesenchymal cells and rich heterochromatin in mesenchymal cells,
      the latter also demonstrating cytoplasmic myofilament dysplasia. Nine cases had
      clinical follow-up ranging from 5 to 48 months, of which 4 patients died.
      CONCLUSIONS: PPB is a rare lung neoplasm of children under the age of 6 years,
      with distinct pathological morphology. PPB may arise from lung or pleura
      mesenchymal cells and has a poor clinical outcome.

PMID- 25582254
TI  - [Morphologic features suggestive of submucosal invasive adenocarcinoma in
      colorectal mucosal biopsy specimens].
AB  - OBJECTIVE: To observe and summarize the morphologic features that may suggest
      submucosal invasive adenocarcinoma in colorectal mucosa biopsy specimens.
      METHODS: The study cohort included 432 colorectal biopsy specimens were obtained
      from 2006 to 2012. All the cases had radical surgery. Basing on the pathologic
      diagnoses, the cases were divided into 366 invasive adenocarcinoma (IAC) and 66
      high-grade intraepithelial neoplasms (HGIN). These two groups were compared.
      RESULTS: In the IAC group, the percentage of tumor forming cribriform structures,
      acute angle-shaped glands, diffuse carcinoma cell proliferation was 61.2%
      (224/366) , 33.8% (124/366) and 7.4% (27/366) , respectively. In the HGIN group,
      cribriform gland structures appeared in 6.0% (4/66) of the cases, while no acute
      angle-shaped gland or diffuse carcinoma cell proliferation was detected. The
      difference of these three characteristics in the two group was statistically
      significant (all P < 0.01). Glandular branching was detected in 89.9% (329/366)
      of IAC cases and 66.7% (44/66) of HGIN cases; this difference was not
      significant. There was no difference in cellular atypia between the two groups.
      Interstitial fibrosis was detected more frequently in the IAC group (85.5%,
      313/366 in IAC versus 0 in HGIN, P < 0.01). In biopsy specimens of IAC, a few
      cases showed neoplastic glands in close contact with large lymphatics, adipose
      tissue, and ganglion. CONCLUSIONS: In colorectal biopsy specimen, the five
      features that suggest submucosal invasion of the neoplastic glands including the
      formation of cribriform structure, angular gland, diffuse carcinoma cells,
      interstitial fibrosis and neoplastic glands in close contact with the thick
      walled vessels.

PMID- 25582255
TI  - [Extracardial rhabdomyoma: a clinicopathologic analysis of 9 cases].
AB  - OBJECTIVE: To investigate the clinicopathologic characteristics, differential
      diagnosis and biological behavior of extracardiac rhabdomyoma. METHODS: Nine
      cases of extracardiac rhabdomyoma diagnosed between January of 1997 and July of
      2014 were reviewed. The clinical, pathologic and immunohistochemical profiles
      were evaluated. RESULTS: There were 5 males and 4 females at diagnosis with age
      ranging from 2 years and three months to 59 years (mean, 37.6 years). Sites
      included the head and neck region (7 cases), chest (1 case ) and vagina wall (1
      case). Clinically, most cases manifested as a subcutaneous nodule or as a
      submucosal polypoid lesion with a mean diameter of 3.2 cm. Histologically, 4 were
      adult-type rhabdomyoma characterized by tightly packed large round or polygonal
      rhabdomyoblasts with abundant eosinophilic to clear cytoplasm; 3 were myxoid
      variant of fetal rhabdomyoma composed of immature myofibrils, spindled and
      primitive mesenchymal cells embedded in a myxoid background, 1 was an
      intermediate form of fetal rhabdomyoma consisting of densely arranged
      differentiated myoblasts with little myxoid stroma; 1 was a genital rhabdomyoma
      composed of elongated or strap-like myoblasts scattered in loose fibrous
      connective tissue. By immunohistochemistry, they showed diffuse and strong
      positivity for desmin, MSA and myoglobin with variable expression of myogenin. A
      case of intermediate type also stained for alpha-smooth muscle actin. Follow up
      data (2 months ~ 17 years) showed local recurrence in one patient 6 months after
      surgery. CONCLUSIONS: Rhabdomyoma is a distinctively rare benign mesenchymal
      tumor showing skeletal muscle differentiation, which may occassionally recur if
      incompletely excised. Familiarity with its clinical and morphological variants is
      essential to avoid misdiagnosing this benign lesion as embryonal
      rhabdomyosarcoma.

PMID- 25582256
TI  - [Benign notochordal cell tumor of cervical vertebrae: a clinicopathologic
      analysis].
AB  - OBJECTIVE: To report 2 rare cases of benign notochordal cell tumor (BNCT),
      according to WHO classification of tumors of soft tissue and bone (4th edition).
      Their radiologic and clincopathologic features and differential diagnosis were
      investigated. METHODS: Two cases of BNCT were studied by retrospective review of
      the clinical, radiologic, pathologic and immunophenotypical findings. Related
      literatures were reviewed at the same time. RESULTS: Case 1 was a 53-year-old
      man, and case 2 was a 61-year-old woman. Radiographically, both patients
      presented with abnormal imaging findings in the fifth cervical vertebral body
      with the lesions located within the bone but without extra osseous mass.
      Histopathologically, the lesions lacked lobular architecture and extracellular
      myxoid matrix. The tumor cells were vacuolated and had centrally or peripherally
      placed round or oval nuclei with small nucleoli, mimicking mature adipocytes. No
      cytological atypia or mitotic figures were seen. The affected bone trabeculae
      were sclerotic and islands of bone marrow were often entrapped within the tumor.
      CONCLUSIONS: Although sharing similar anatomic distribution and immunophenotype
      to those of chordoma, BNCT has distinct radiologic and pathologic features and
      different treatment and prognosis. The differential diagnosis between BNCT and
      chordoma requires detailed clinical, radiologic and histopathologic evaluations.

PMID- 25582257
TI  - [Application of fluorescence in-situ hybridization polyclonal probes in diagnosis
      of alveolar soft part sarcoma].

PMID- 25582259
TI  - [Oncocytic papillary renal cell carcinoma:report of a case].

PMID- 25582258
TI  - [Fluorescence in situ hybridization performed on paraffin sections after
      immunohistochemical staining].

PMID- 25582260
TI  - [High-grade lung adenocarcinoma of fetal lung type:report of a case].

PMID- 25582261
TI  - [Atypical extraventricular neurocytoma: report of a case].

PMID- 25582262
TI  - [Histopathologic and immunohistochemical markers for testicular germ cell
      tumors].

PMID- 25582263
TI  - [Benign mimickers of prostatic carcinoma on needle biopsy and transurethral
      resection specimens].

PMID- 25582264
TI  - [MicroRNA as prognostic biomarkers in prostatic cancer].

PMID- 25582265
TI  - [Progress in research on long non-coding RNA in tumor metastasis and drug
      resistance].

PMID- 25582266
TI  - Stress, Depression, and Metabolism: Replies to Bohan Brown et al. and Barton and
      Yancy.

PMID- 25582267
TI  - Determining the Culprit: Stress, Fat, or Carbohydrates.

PMID- 25582268
TI  - Paired Pulse Depression in the Subcallosal Cingulate Region of Depression
      Patients.

PMID- 25582269
TI  - Left prefrontal high-frequency repetitive transcranial magnetic stimulation for
      the treatment of schizophrenia with predominant negative symptoms: a sham
      controlled, randomized multicenter trial.
AB  - BACKGROUND: Investigators are urgently searching for options to treat negative
      symptoms in schizophrenia because these symptoms are disabling and do not respond
      adequately to antipsychotic or psychosocial treatment. Meta-analyses based on
      small proof-of-principle trials suggest efficacy of repetitive transcranial
      magnetic stimulation (rTMS) for the treatment of negative symptoms and call for
      adequately powered multicenter trials. This study evaluated the efficacy of 10-Hz
      rTMS applied to the left dorsolateral prefrontal cortex for the treatment of
      predominant negative symptoms in schizophrenia. METHODS: A multicenter
      randomized, sham-controlled, rater-blinded and patient-blinded trial was
      conducted from 2007-2011. Investigators randomly assigned 175 patients with
      schizophrenia with predominant negative symptoms and a high-degree of illness
      severity into two treatment groups. After a 2-week pretreatment phase, 76
      patients were treated with 10-Hz rTMS applied 5 days per week for 3 weeks to the
      left dorsolateral prefrontal cortex (added to the ongoing treatment), and 81
      patients were subjected to sham rTMS applied similarly. RESULTS: There was no
      statistically significant difference in improvement in negative symptoms between
      the two groups at day 21 (p = .53, effect size = .09) or subsequently through day
      105. Also, symptoms of depression and cognitive function showed no differences in
      change between groups. There was a small, but statistically significant,
      improvement in positive symptoms in the active rTMS group (p = .047, effect size
      = .30), limited to day 21. CONCLUSIONS: Application of active 10-Hz rTMS to the
      left dorsolateral prefrontal cortex was well tolerated but was not superior
      compared with sham rTMS in improving negative symptoms; this is in contrast to
      findings from three meta-analyses.

PMID- 25582271
TI  - Erythrocyte genotyping for transfusion-dependent patients at the Azienda
      Universitaria Policlinico of Naples.
AB  - BACKGROUND AND OBJECTIVES: Although minor erythrocyte antigens are not considered
      clinically significant in sporadic transfusions, they may be relevant for multi
      transfusion patients. When serological assay is not conceivable, molecular
      genotyping allows predicting the red blood cell phenotype, extending the typing
      until minor blood groups. The aim of this study was to evaluate the utility of
      blood group genotyping and compare the molecular typing of erythrocyte antigens
      with the established serological methods. MATERIALS AND METHODS: We selected 225
      blood donors and 50 transfusion-dependent patients at the Division of
      Immunohematology of the Second University of Naples. Blood samples were analyzed
      with NEO Immucor automated system and genotyped for 38 red blood cell antigens
      and phenotypic variants with the kit HEA BeadChipTM. The comparative study was
      conducted for RhCE and Kell antigens whose typing is available with both methods.
      RESULTS: We observed a good correlation between serological and molecular methods
      for donors that were concordant for 99.5% (224/225) and discordant for 0.5%
      (1/225). Patients resulted concordant only for 46.0% (23/50) and discordant for
      54.0% (27/50); discrepancies were 46.0% (23/50) and 8.0% (4/50) for RhCE and Kell
      systems respectively. Through molecular genotyping we also identified
      polymorphisms in RhCE, Kell, Duffy, Colton, Lutheran and Scianna loci in donors
      and patients. CONCLUSIONS: Blood group genotyping is particularly useful for poly
      transfused patients. Molecular analysis confirms and extends serological test
      data and then allows us to obtain a better match. This molecular assay can be
      used in the future to prevent alloimmunization in transfusion-dependent patients.

PMID- 25582272
TI  - Weak D Type 4.2.2 (DAR1.2) in an African child: Serology and molecular
      characterization.
AB  - The weak D phenotype is represented by a group of RHD genotypes that code for
      alterated RhD proteins associated with a reduced RhD expression on red blood
      cell. By routine serology, some partial D variants are likely to be missed. In
      this report we describe the case of a three-year-old Black African child with a
      "unclear" reaction with monoclonal anti-D. We analyzed the blood sample of the
      child with different methods to conclude that it is a case of DAR 1.2 (weak D
      4.2.2) and that it must be transfused with D negative erithrocytes. 

PMID- 25582270
TI  - Comparison of cryopreservation bags for hematopoietic progenitor cells using a
      WBC-enriched product.
AB  - Hematopoietic progenitor cells (HPC) are stored in cryopreservation bags that are
      resistant to liquid nitrogen. Since Cryocyte bags of Baxter (B-bags) are no
      longer available, an alternative bag was sought. Also, the influence of freezing
      volume was studied. Miltenyi Biotec (MB)- and MacoPharma (MP)-bags passed the
      integrity tests without failure. Comparing MB- and MP-bags with B-bags, no
      difference in WBC recovery or viability was found when using a WBC-enriched
      product as a "dummy" HPC product. Further, a freezing volume of 30 mL resulted in
      better WBC recovery and viability than 60 mL. Additonal studies using real HPC
      might be necessary. 

PMID- 25582273
TI  - Vaccines 'on demand': science fiction or a future reality.
AB  - INTRODUCTION: Self-amplifying mRNA vaccines are being developed as a platform
      technology with potential to be used for a broad range of targets. The synthetic
      production methods for their manufacture, combined with the modern tools of
      bioinformatics and synthetic biology, enable these vaccines to be produced
      rapidly from an electronic gene sequence. Preclinical proof of concept has so far
      been achieved for influenza, respiratory syncytial virus, rabies, Ebola,
      cytomegalovirus, human immunodeficiency virus and malaria. AREAS COVERED: This
      editorial highlights the key milestones in the discovery and development of self
      amplifying mRNA vaccines, and reviews how they might be used as a rapid response
      platform. The paper points out how future improvements in RNA vector design and
      non-viral delivery may lead to decreases in effective dose and increases in
      production capacity. EXPERT OPINION: The prospects for non-viral delivery of self
      amplifying mRNA vaccines are very promising. Like other types of nucleic acid
      vaccines, these vaccines have the potential to draw on the positive attributes of
      live-attenuated vaccines while obviating many potential safety limitations.
      Hence, this approach could enable the concept of vaccines on demand as a rapid
      response to a real threat rather than the deployment of strategic stockpiles
      based on epidemiological predictions for possible threats.

PMID- 25582274
TI  - Inner ocular blood flow responses to an acute decrease in blood pressure in
      resting humans.
AB  - Whether inner ocular vessels have an autoregulatory response to acute
      fluctuations in blood pressure is unclear. We tried to examine the validity of
      acute hypotension elicited by thigh-cuff release as to assess the dynamic
      autoregulation in the ocular circulation. Blood flow velocity in the superior
      nasal and inferior temporal retinal arterioles, and in the retinal and choroidal
      vasculature were measured with the aid of laser speckle flowgraphy before and
      immediately after an acute decrease in blood pressure in 20 healthy subjects.
      Acute hypotension was induced by a rapid release of bilateral thigh occlusion
      cuffs that had been inflated to 220 mmHg for 2 min. The ratio of the relative
      change in retinal and choroidal blood flow velocity to the relative change in
      mean arterial blood pressure (MAP) was calculated. Immediately after cuff
      release, the MAP and blood flows in the all ocular target vessels decreased
      significantly from the baseline values obtained before thigh-cuff release. The
      ratio of the relative change in inner ocular blood flow velocity to that in the
      MAP exceeded 1% / %mmHg. An explicit dynamic autoregulation in inner ocular
      vessels cannot be demonstrated in response to an acute hypotension induced by the
      thigh-cuff release technique. 

PMID- 25582275
TI  - Cytidine deaminase polymorphism predicts toxicity of gemcitabine-based
      chemotherapy.
AB  - BACKGROUND: The aim of this study was to ascertain whether single nucleotide
      polymorphisms of cytidine deaminase (CDA), a key enzyme in the metabolism pathway
      of gemcitabine, could predict clinical outcomes of cancer patients with
      gemcitabine-based chemotherapy. METHODS: We searched MEDLINE and EMBASE up to
      January 2013 to identify eligible studies. A rigorous quality assessment of
      eligible studies was conducted according to the Newcastle-Ottawa Quality
      Assessment Scale. For each included study, the overall survival (OS), overall
      response rate (ORR) and toxicities were extracted and pooled using random-effects
      model. RESULTS: In total, data from 13 studies were included. CDA 208A>G and CDA
      435C>T were not included in quantified synthesis due to limited data. CDA 79A>C
      polymorphism was not significantly associated with OS; however, patients carrying
      the variant CDA 79C allele were likely to have a poor survival, hazard ratio
      (HR)=1.03, 95% CI 0.957-1.27 (AC+CC vs. AA). CDA 79A>C polymorphism did not
      correlated with ORR, odds ratio (OR)=0.719, 95% CI 0.363-1.425 (AC+CC vs. AA).
      However, patients with the variant CDA 79C allele would experience more grade >=
      3 leucopenia (OR=2.933, 95% CI 1.357-6.605) and tended to have more severe
      neutropenia (OR=1.313, 95% CI 0.157-10.981). CONCLUSIONS: These results suggest
      that CDA 79A>C polymorphisms is a potential biomarker for toxicity of gemcitabine
      based chemotherapy and a CDA testing before gemcitabine administration is
      preferred.

PMID- 25582276
TI  - IFPA Gabor Than Award Lecture: Recognition of placental failure is key to saving
      babies' lives.
AB  - In high-income countries, placental failure is implicated in up to 65% of cases
      of stillbirth. Placental failure describes the situation where the placenta
      cannot meet the fetus' needs and may be the end-result of a variety of underlying
      pathological processes evident in the placental disc, membranes and umbilical
      cord. These include lesions with genetic, environmental, infectious,
      inflammatory, mechanical, metabolic, traumatic or vascular origin. Investigation
      of placental tissue from stillbirths and from pregnancies at an increased risk of
      stillbirth has demonstrated changes in macroscopic and microscopic structure
      which are themselves related to abnormal placental function. A better
      understanding and identification of placental failure may improve the management
      of pregnancy complications and of pregnancies after stillbirth (which have a 5
      fold increased risk of stillbirth). The majority of current antenatal tests focus
      on the fetus and its response to the intrauterine environment; few of these
      investigations reduce stillbirths in low-risk pregnancies. However, some
      currently used investigations reflect placental development, structure and
      vascular function, while other investigations employed in clinical research
      settings such as the evaluation of placental structure and shape have a good
      predictive value for adverse fetal outcome. In addition, recent studies suggest
      that biomarkers of placental inflammation and deteriorating placental function
      can be detected in maternal blood suggesting that holistic evaluation of
      placental structure and function is possible. We anticipate that development of
      reliable tests of placental structure and function, coupled to assessment of
      fetal wellbeing offer a new opportunity to identify pregnancies at risk of
      stillbirth and to direct novel therapeutic strategies to prevent it. 

PMID- 25582277
TI  - Impact of Rhesus disease on the global problem of bilirubin-induced neurologic
      dysfunction.
AB  - Clinical experience with Rhesus (Rh) disease and its post-icteric sequelae is
      limited among high-income countries because of nearly over four decades of
      effective prevention care. We hypothesized that Rh disease is prevalent in other
      regions of the world because it is likely that protection is limited or non
      existent. Following a worldwide study, it has been concluded that Rh hemolytic
      disease is a significant public health problem resulting in stillbirths and
      neonatal deaths, and is a major cause of severe hyperbilirubinemia with its
      sequelae, kernicterus and bilirubin-induced neurologic dysfunction. Knowing that
      effective Rh-disease prophylaxis depends on maternal blood-type screening,
      healthcare afforded to the high-risk mothers needs to be free of bottlenecks and
      coupled with unfettered access to effective Rh-immunoglobulin. Future studies
      that match the universal identification of Rh-negative status of women and
      targeted use of immunoprophylaxis to prevent childhood bilirubin neurotoxicity
      are within reach, based on vast prior experiences. 

PMID- 25582278
TI  - EGFR L858R mutation is associated with lung adenocarcinoma patients with dominant
      ground-glass opacity.
AB  - OBJECTIVES: To retrospectively identify quantitative computed tomographic (CT)
      features that correlate with the three major driver gene mutations in surgically
      resected lung adenocarcinomas with dominant ground-glass opacity (GGO) stratified
      by the International Association for the Study of Lung Cancer (IASLC), American
      Thoracic Society (ATS), and European Respiratory Society (ERS) classification in
      a Chinese cohort of patients. MATERIALS AND METHODS: Surgically resected lung
      adenocarcinomas from Shanghai Pulmonary Hospital were enrolled. EGFR, KRAS and
      EML4-ALK mutations were detected by qPCR. Clinical and pathological
      characteristics including gender, age, TNM stage, smoking status and CT pattern
      were analyzed. Histologic subtype was classified according to IASLC/ATS/ERS
      classification. At preoperative chest CT, the percentage of GGO volume, diameter,
      solid volume and total tumor volume of each tumor were measured by using a
      semiautomated algorithm. Distribution of driver gene mutations was evaluated by
      using the Fisher exact test, the Student's t test, and Pearson correlation
      analysis. RESULTS AND CONCLUSION: 788 in total and 158 GGO tumors were taken in
      this cohort. GGO pattern occurred at a significantly higher frequency in younger,
      female and non-smoking patients. EGFR/KRAS mutations and EML4-ALK fusions were
      similar between GGO and solid adenocarcinomas. GGO volume and diameter showed
      correlation with EGFR mutation. With regard to association between lung
      adenocarcinoma histological subtypes and GGO features, GGO proportion was
      significantly higher in lepidic predominant adenocarcinomas, including
      adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic
      predominant invasive adenocarcinoma. No significant differences of driver gene
      mutations were found between subtypes of lung adenocarcinoma. It is important
      that we understand GGO lesions of lung adenocarcinoma to identify molecular
      biomarkers including EGFR, KRAS and EML4-ALK. These markers would offer useful
      information for determining the appropriate strategy to treat lung adenocarcinoma
      with GGO lesions detected by helical CT.

PMID- 25582280
TI  - Prevalence and reasons for use of electronic cigarettes among smokers: Findings
      from the International Tobacco Control (ITC) Netherlands Survey.
AB  - BACKGROUND: Not much is known about how people in the Netherlands respond to
      electronic cigarettes (e-cigarettes); how many know about them, which people try
      them, keep using them and why, and what are changes over time regarding awareness
      and use? METHODS: We used samples of smokers aged 15 years and older from 2008
      (n=1820), 2010 (n=1702), 2013 (n=1530), and 2014 (n=1550) as part of the
      International Tobacco Control (ITC) Netherlands Survey. Reasons for use and
      characteristics of smokers were examined using the sample from 2014. Logistic
      regression analyses were conducted to evaluate the associations between smoking
      related variables with ever trying e-cigarettes and current e-cigarette use.
      RESULTS: In 2014, 91.4% of Dutch smokers reported being aware of e-cigarettes
      (97.1% in 2008, 89.2% in 2010, and 85.5% in 2013), 40.0% reported having ever
      tried them (13.4% in 2008, 14.5% in 2010, and 19.6% in 2013), and 15.9% were
      currently using them (4.0% in 2008, 1% in 2010, and 3.9% in 2013). The main
      reason given for using e-cigarettes was to reduce the number of regular
      cigarettes smoked per day (79%). Ever trying e-cigarettes among those aware of e
      cigarettes was associated with being young, smoking more regular cigarettes per
      day, having made a quit attempt in the last year, having used smoking cessation
      pharmacotherapy in the last year, and reporting high awareness of the price of
      regular cigarettes. Smokers who kept using e-cigarettes had a higher educational
      background, had higher harm awareness for the health of others, and were less
      likely to have a total smoking ban at home. CONCLUSION: E-cigarettes are
      increasingly used by Dutch smokers. Commonly endorsed motivations for current e
      cigarette use were to reduce tobacco smoking and because e-cigarettes are
      considered to be less harmful than tobacco cigarettes.

PMID- 25582279
TI  - Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results
      from two phase 3 trials.
AB  - PURPOSE: To evaluate the structure-modifying and symptom efficacy, as well as
      safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC
      carrier (a molecule based on Eligen((r)) technology), in osteoarthritis (OA)
      patients with moderate to severe knee pain and joint structural damage classified
      as Kellgren and Lawrence (KL)2-3. METHODS AND DESIGN: This is the combined
      reporting of two randomized, double-blind, multi-center, placebo-controlled
      trials (CSMC021C2301 and CSMC021C2302), evaluating the efficacy and safety of
      oral sCT in patients with painful knee OA with structural manifestations,
      enrolling 1176 and 1030 patients, respectively. Study subjects were randomized
      (1:1) to oral sCT 0.8 mg twice daily or placebo (PBO) for 24 months. The primary
      efficacy objectives were to examine the treatment effect compared to placebo on
      change over 24 months in joint space width (JSW) in the signal knee measured by X
      ray, and to examine the change in pain and function using the Western Ontario and
      McMaster Universities Osteoarthritis (WOMAC) questionnaire. Other study
      parameters included patient and physician global assessment, and biochemical
      markers of bone (CTX-I) and cartilage degradation (CTX-II). RESULTS: At the 24
      month endpoint there was no statistically significant treatment effect on joint
      space narrowing (JSN) in any of the two studies. In CSMC021C2301 there was a
      treatment effect on WOMAC (sum of pain, function, stiffness, and total scores) as
      well as on the biomarkers of bone and joint metabolism, but due to the
      hierarchical testing procedure the treatment effect was not claimed statistically
      significant. CONCLUSIONS: The present formulation of oral sCT did not provide
      reproducible clinical benefits in patients with symptomatic knee OA (NCT00486434,
      NCT00704847).

PMID- 25582281
TI  - Global patterns of domestic cannabis cultivation: sample characteristics and
      patterns of growing across eleven countries.
AB  - BACKGROUND: This article aims to provide an overview of: demographic
      characteristics; experiences with growing cannabis; methods and scale of growing
      operations; reasons for growing; personal use of cannabis and other drugs;
      participation in cannabis and other drug markets; contacts with the criminal
      justice system for respondents to an online survey about cannabis cultivation
      drawn from eleven countries (N=6530). Important similarities and differences
      between the national samples recruited will be discussed. METHODS: This paper
      utilizes data from the online web survey of predominantly 'small-scale' cannabis
      cultivators in eleven countries conducted by the Global Cannabis Cultivation
      Research Consortium (GCCRC). Here we focus primarily on descriptive statistics to
      highlight key similarities and differences across the different national samples.
      RESULTS: Overall there was a great deal of similarity across countries in terms
      of: demographic characteristics; experiences with growing cannabis; methods and
      scale of growing operations; reasons for growing; use of cannabis and other
      drugs; participation in cannabis and other drug markets, and; contacts with the
      criminal justice system. In particular, we can recognise that a clear majority of
      those small-scale cannabis cultivators who responded to our survey are primarily
      motivated for reasons other than making money from cannabis supply and have
      minimal involvement in drug dealing or other criminal activities. CONCLUSIONS:
      These growers generally come from 'normal' rather than 'deviant' backgrounds.
      Some differences do exist between the samples drawn from different countries
      suggesting that local factors (political, geographical, cultural, etc.) may have
      some influence on how small-scale cultivators operate, although differences in
      recruitment strategies in different countries may also account for some
      differences observed.

PMID- 25582282
TI  - Parameters influencing FVIII pharmacokinetics in patients with severe and
      moderate haemophilia A.
AB  - In haemophilia A patients factor VIII (FVIII) recovery and half-life can vary
      substantially. There are parameters known to modulate FVIII pharmacokinetics
      (PK), but they explain only about 34% of the variability. The aim of this study
      was to identify new parameters that influence FVIII PK and thus to expand the
      current knowledge. FVIII PK were determined in 42 haemophilia A patients (37
      severe, 5 moderate) without inhibitor. Patients' characteristics and laboratory
      parameters were evaluated for an association with FVIII PK. We analysed plasma
      levels of low-density lipoprotein receptor-related protein 1 (LRP1) and protein C
      (PC) activity, which had been hypothesized to influence FVIII activity.
      Furthermore, four variations in intron 6 of the LRP1 gene, which had been shown
      to influence LRP1, were investigated. FVIII half-life differed widely from 6.2 to
      20.7 h, with a median of 10.0 h. Patients with blood group O had shorter FVIII
      half-life compared to patients with non-O blood group (median FVIII half-life 9.0
      h vs. 10.4 h, P = 0.018). Age was significantly associated with FVIII half-life
      (r = 0.32, P = 0.035). Besides age, also VWF antigen (r = 0.52, P < 0.001) and
      blood group (r = -0.37, P = 0.015) was associated with FVIII half-life. No
      correlation was found with FVIII- or LRP1-genotype, LRP1 or PC concentrations.
      Our data showed large differences in FVIII PK between individual patients and
      revealed age, blood group and VWF levels as important determining factors for
      FVIII half-life. FVIII genotype or levels of LRP1 or PC had no influence on FVIII
      PK. 

PMID- 25582283
TI  - The emerging role of biosimilar epoetins in nephrology in the United States.
AB  - Biologic drugs, including epoetin, continue to play an important role in the
      management of medical conditions. However, biologics are costly and soon many of
      the patents on these drugs will expire, making way for non-brand name products
      (ie, biosimilars). It is only by introducing competition to the marketplace that
      costs will de-escalate. In Europe, a specific regulatory pathway for approving
      biosimilars has been in place since 2005. A similar review pathway in the United
      States has been developed by the US Food and Drug Administration. These
      guidelines for approving biosimilars are stringent, requiring preclinical
      pharmacodynamic and toxicologic studies, clinical studies to demonstrate
      bioequivalence and efficacy, and long-term postmarketing studies to monitor drug
      safety. Biosimilar epoetin has been used in Europe since 2007, and a wealth of
      data has been collected. These studies and reports indicate that the efficacy and
      safety profiles of biosimilar epoetin are similar to those of originator epoetin
      alfa. Biosimilars of epoetin alfa are expected to be among the first biosimilar
      agents to be approved for use in the United States. The availability of lower
      cost epoetins may have significant impact on the treatment of anemia of chronic
      kidney disease.

PMID- 25582284
TI  - Research priority setting in kidney disease: a systematic review.
AB  - BACKGROUND: Resources for research are insufficient to cover all unanswered
      questions, and therefore difficult choices about allocation must be made.
      Recently there has been a move toward more patient-centered research. This study
      aims to evaluate approaches to research prioritization in kidney disease and
      describe research priorities of patients with kidney disease, their caregivers,
      the health care providers involved in their care, and policy makers. STUDY
      DESIGN: Systematic review. SETTING & POPULATION: Studies that elicited patient,
      caregiver, health care provider, or policy maker priorities for research in
      kidney disease were included. SEARCH STRATEGY & SOURCES: MEDLINE, EMBASE,
      PsycINFO, and CINAHL were searched to May 2014. ANALYTICAL APPROACH: Descriptive
      synthesis. RESULTS: We identified 16 studies (n=2,365 participants) conducted in
      the United States, the Netherlands, Australia, Canada, and internationally. Only
      4 (25%) studies explicitly involved patients. Various priority-setting methods
      were used, including the Delphi technique, expert panels, consensus conference,
      ranking or voting surveys, focus groups, and interviews, of which the process was
      described in detail by 11 (69%) studies. The priority areas for research most
      frequently identified across studies were prevention of acute kidney injury,
      prevention of chronic kidney disease progression, fluid and diet restrictions,
      improving vascular access, kidney transplant survival, access to transplantation,
      patient education, and psychosocial impact of chronic kidney disease.
      LIMITATIONS: Most studies were conducted in high-income countries. CONCLUSIONS:
      The priorities identified by kidney disease research priority-setting exercises
      are broad ranging, but patient involvement is uncommon and the processes often
      are incompletely described. Establishing research priorities using a prespecified
      and transparent process that engages patients, caregivers, and health care
      providers is needed to ensure that resources are invested to answer questions
      that address the shared priorities in kidney disease.

PMID- 25582286
TI  - Oak Stave Oxygen Permeation: A New Tool To Make Barrels with Different Wine
      Oxygenation Potentials.
AB  - The aim of this study was to classify rough staves according to their
      permeability to oxygen by measuring their transmission rate to assess the
      capacity to build barrels with high and low oxygen transmission rates (OTRs). The
      ability to assess the OTR would be important for better understanding and
      controlling the aging process of wine in barrels. To accomplish this, we built a
      device that measures the OTR of rough staves under the same conditions as those
      in a full barrel, in which the stave is in contact with a liquid solution on one
      face and with a diffusing gas on the opposite face. A total of 69 rough staves
      were classified to yield a high-OTR group, with a mean 2.6 times higher than the
      mean of the low-OTR group. A high-OTR barrel and a low-OTR barrel were
      constructed, and we confirmed that the stave OTR decreased between 3- and 4.5
      fold in the barrels and that the high-OTR barrel allowed the entry of twice the
      concentration of oxygen compared to the low-OTR barrel. These results confirmed
      the capacity to classify rough staves and build barrels with different OTRs.

PMID- 25582285
TI  - Patient and caregiver perspectives on home hemodialysis: a systematic review.
AB  - BACKGROUND: Although home hemodialysis (HD) is associated with better survival
      compared with hospital HD, the burden of treatment may be intensified for
      patients and their caregivers and deter patients from this treatment choice. We
      describe patient and caregiver perspectives and experiences of home HD to inform
      home HD programs that align with patient preferences. STUDY DESIGN: Systematic
      review of qualitative studies. SETTING & POPULATION: Adults with chronic kidney
      disease and caregivers of both home and hospital dialysis patients who expressed
      opinions about home HD. SEARCH STRATEGY & SOURCES: MEDLINE, EMBASE, PsycINFO,
      CINAHL, and reference lists were searched to October 2013. ANALYTICAL APPROACH:
      Thematic synthesis. RESULTS: 24 studies involving 221 patients (home HD [n=109],
      hospital HD [n=97], and predialysis [n=15]) and 121 caregivers were eligible. We
      identified 5 themes: vulnerability of dialyzing independently (fear of self
      needling, feeling unqualified, and anticipating catastrophic complications), fear
      of being alone (social isolation and medical disconnection), concern of family
      burden (emotional demands on caregivers, imposing responsibility, family
      involvement, and medicalizing the home), opportunity to thrive (re-establishing a
      healthy self-identity, gaining control and freedom, strengthening relationships,
      experiencing improved health, and ownership of decision), and appreciating
      medical responsiveness (attentive monitoring and communication, depending on
      learning and support, developing readiness, and clinician validation).
      LIMITATIONS: Non-English articles were excluded. CONCLUSIONS: Patients and
      caregivers perceive that home HD offers the opportunity to thrive; improves
      freedom, flexibility, and well-being; and strengthens relationships. However,
      some voice anxiety and fear about starting home HD due to the confronting nature
      of the treatment and isolation from medical and social support. Acknowledging and
      addressing these apprehensions can improve the delivery of predialysis and home
      HD programs to better support patients and caregivers considering home HD.

PMID- 25582287
TI  - Hippocampal Neuroprotection by Minocycline and Epigallo-Catechin-3-Gallate
      Against Cardiopulmonary Bypass-Associated Injury.
AB  - Surgical correction of congenital cardiac malformations mostly implies the use of
      cardiopulmonary bypass (CPB). However, a possible negative impact of CPB on
      cerebral structures like the hippocampus cannot be neglected. Therefore, we
      investigated the effect of CPB on hippocampus CA1 and CA3 regions without or with
      the addition of epigallocatechin-3-gallate (EGCG) or minocycline. We studied 42
      piglets and divided them into six experimental groups: control without or with
      EGCG or minocycline, CPB without or with EGCG or minocycline. The piglets
      underwent 90 minutes CPB and subsequently, a 120-minute recovery and reperfusion
      phase. Thereafter, histology of the hippocampus was performed and the adenosine
      triphosphate (ATP) content was measured. Histologic evaluation revealed that CPB
      produced a significant peri-cellular edema in both CA regions. Moreover, we found
      an increased number of cells stained with markers for hypoxia, apoptosis and
      nitrosative stress. Most of these alterations were significantly reduced to or
      near to control levels by application of EGCG or minocycline. ATP content was
      significantly reduced within the hippocampus after CPB. This reduction could not
      be antagonized by EGCG or minocycline. In conclusion, CPB had a significant
      negative impact on the integrity of hippocampal neural cells. This cellular
      damage could be significantly attenuated by addition of EGCG or minocycline. 

PMID- 25582288
TI  - Microglia in neuronal plasticity: Influence of stress.
AB  - The central nervous system (CNS) has previously been regarded as an immune
      privileged site with the absence of immune cell responses but this dogma was not
      entirely true. Microglia are the brain innate immune cells and recent findings
      indicate that they participate both in CNS disease and infection as well as
      facilitate normal CNS function. Microglia are highly plastic and play integral
      roles in sculpting the structure of the CNS, refining neuronal circuitry and
      connectivity, and contribute actively to neuronal plasticity in the healthy
      brain. Interestingly, psychological stress can perturb the function of microglia
      in association with an impaired neuronal plasticity and the development of
      emotional behavior alterations. As a result it seemed important to describe in
      this review some findings indicating that the stress-induced microglia
      dysfunction may underlie neuroplasticity deficits associated to many mood
      disorders. This article is part of a Special Issue entitled 'Neuroimmunology and
      Synaptic Function'. 

PMID- 25582291
TI  - Obesity, adipokines and neuroinflammation.
AB  - Global levels of obesity are reaching epidemic proportions, leading to a dramatic
      increase in incidence of secondary diseases and the significant economic burden
      associated with their treatment. These comorbidities include diabetes,
      cardiovascular disease, and some psychopathologies, which have been linked to a
      low-grade inflammatory state. Obese individuals exhibit an increase in
      circulating inflammatory mediators implicated as the underlying cause of these
      comorbidities. A number of these molecules are also manufactured and released by
      white adipose tissue (WAT), in direct proportion to tissue mass and are
      collectively known as adipokines. In the current review we focused on the role of
      two of the better-studied members of this family namely, leptin and adiponectin,
      with particular emphasis on their role in neuro-immune interactions,
      neuroinflammation and subsequent brain diseases. This article is part of a
      Special Issue entitled 'Neuroimmunology and Synaptic Function'. 

PMID- 25582292
TI  - Genetic exploration of the role of acid-sensing ion channels.
AB  - Advanced gene targeting technology and related tools in mice have been
      incorporated into studies of acid-sensing ion channels (ASICs). A single ASIC
      subtype can be knocked out specifically and screened thoroughly for expression in
      the nervous system at the cellular level. Mapping studies have further shed light
      on the initiation and identification of related behavioral phenotypes. Here we
      review studies involving genetically engineered mouse models used to investigate
      the physiological function of individual ASIC subtypes: ASIC1 (and ASIC1a),
      ASIC2, ASIC3 and ASIC4. We discuss the detailed expression studies and
      significant phenotypes revealed with gene knockout for most known Asic subtypes.
      Each strategy designed to manipulate mouse genetics has advantages and
      disadvantages. We discuss the limitations of these Asic-knockout models and
      propose future directions to solve the genetic issues. This article is part of
      the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'. 

PMID- 25582290
TI  - Two aspects of ASIC function: Synaptic plasticity and neuronal injury.
AB  - Extracellular brain pH fluctuates in both physiological and disease conditions.
      The main postsynaptic proton receptor is the acid-sensing ion channels (ASICs).
      During the past decade, much progress has been made on protons, ASICs, and
      neurological disease. This review summarizes the recent progress on synaptic role
      of protons and our current understanding of how ASICs contribute to various types
      of neuronal injury in the brain. This article is part of the Special Issue
      entitled 'Acid-Sensing Ion Channels in the Nervous System'. 

PMID- 25582289
TI  - Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential
      pathway to modulate aggression and related behavioral states.
AB  - The co-morbidity between smoking and mood disorders is striking. Preclinical and
      clinical studies of nicotinic effects on mood, anxiety, aggression, and related
      behaviors, such as irritability and agitation, suggest that smokers may use the
      nicotine in tobacco products as an attempt to self-medicate symptoms of affective
      disorders. The role of nicotinic acetylcholine receptors (nAChRs) in circuits
      regulating mood and anxiety is beginning to be elucidated in animal models, but
      the mechanisms underlying the effects of nicotine on aggression-related
      behavioral states (ARBS) are still not understood. Clinical trials of nicotine or
      nicotinic medications for neurological and psychiatric disorders have often found
      effects of nicotinic medications on ARBS, but few trials have studied these
      outcomes systematically. Similarly, the increase in ARBS resulting from smoking
      cessation can be resolved by nicotinic agents, but the effects of nicotinic
      medications on these types of mental states and behaviors in non-smokers are less
      well understood. Here we review the literature on the role of nAChRs in
      regulating mood and anxiety, and subsequently on the closely related construct of
      ARBS. We suggest avenues for future study to identify how nAChRs and nicotinic
      agents may play a role in these clinically important areas. This article is part
      of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From
      Molecular Biology to Cognition'. 

PMID- 25582293
TI  - The dichotomized role for acid sensing ion channels in musculoskeletal pain and
      inflammation.
AB  - Chronic muscle pain affects between 11 and 24% of the world's population with the
      majority of people experiencing musculoskeletal pain at some time in their life.
      Acid sensing ion channels (ASICs) are important sensors of modest decreases in
      extracellular pH that occur within the physiological range. These decreases in
      extracellular pH occur in response to inflammation, fatiguing exercise, and
      ischemia. Further, injection of acidic saline into muscle produces enhanced
      nociceptive behaviors in animals and pain in human subjects. Of the different
      types of ASICs, ASIC3 and ASIC1 have been implicated in transmission of
      nociceptive information from the musculoskeletal system. The current review will
      provide an overview of the evidence for ASIC3 and ASIC1 in musculoskeletal pain
      in both inflammatory and non-inflammatory models. This article is part of the
      Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'. 

PMID- 25582296
TI  - Receptor for protons: First observations on Acid Sensing Ion Channels.
AB  - The history of ASICs began in 1980 with unexpected observation. The concept of
      highly selective Na(+) current gated by specific receptors for protons was not
      easily accepted. It took 16 years to get these receptor/channels cloned and start
      a new stage in their investigation. "The receptor for protons" became ASIC
      comprising under this name a family of receptor/channels ubiquitous for mammalian
      nervous system, both peripheral and central. The role of ASICs as putative
      nociceptors was suggested almost immediately after their discovery. This role
      subsequently was proven in many forms of pain-related phenomena. Many other
      functions of ASICs have been also found or primed for speculations both in
      physiology and in disease. Despite the width of field and strength of efforts,
      numerous basic questions are to be answered before we understand how the local
      changes in pH in the nervous tissue transform into electric and messenger
      signaling via ASICs as transducers. This article is part of the Special Issue
      entitled 'Acid-Sensing Ion Channels in the Nervous System'. 

PMID- 25582294
TI  - Acid-sensing ion channels in gastrointestinal function.
AB  - Gastric acid is of paramount importance for digestion and protection from
      pathogens but, at the same time, is a threat to the integrity of the mucosa in
      the upper gastrointestinal tract and may give rise to pain if inflammation or
      ulceration ensues. Luminal acidity in the colon is determined by lactate
      production and microbial transformation of carbohydrates to short chain fatty
      acids as well as formation of ammonia. The pH in the oesophagus, stomach and
      intestine is surveyed by a network of acid sensors among which acid-sensing ion
      channels (ASICs) and acid-sensitive members of transient receptor potential ion
      channels take a special place. In the gut, ASICs (ASIC1, ASIC2, ASIC3) are
      primarily expressed by the peripheral axons of vagal and spinal afferent neurons
      and are responsible for distinct proton-gated currents in these neurons. ASICs
      survey moderate decreases in extracellular pH and through these properties
      contribute to a protective blood flow increase in the face of mucosal acid
      challenge. Importantly, experimental studies provide increasing evidence that
      ASICs contribute to gastric acid hypersensitivity and pain under conditions of
      gastritis and peptic ulceration but also participate in colonic hypersensitivity
      to mechanical stimuli (distension) under conditions of irritation that are not
      necessarily associated with overt inflammation. These functional implications and
      their upregulation by inflammatory and non-inflammatory pathologies make ASICs
      potential targets to manage visceral hypersensitivity and pain associated with
      functional gastrointestinal disorders. This article is part of the Special Issue
      entitled 'Acid-Sensing Ion Channels in the Nervous System'. 

PMID- 25582297
TI  - Simultaneous Delorme's procedure and inter-sphinteric prosthetic implant for the
      treatment of rectal prolapse and faecal incontinence: preliminary experience and
      literature review.
AB  - AIM: Rectal prolapse is a distressing condition affecting mostly elderly patients
      and females. Delorme's procedure is frequently performed since it offers good
      results and is burdened by a particularly low morbidity. Faecal Incontinence is
      associated with prolapse in a large percentage of patients, due to the sphincter
      damage caused by the prolapsed rectum through the anal canal. Prolapse resection
      is often ineffective in treating incontinence, and further specific procedures
      are frequently required. At present, no data are available on combined Delorme's
      procedure with the implant of Bulking Agents for the simultaneous treatment of
      rectal prolapse and faecal incontinence. METHOD: Three patients affected by
      complete external rectal prolapse underwent simultaneous Delorme's procedure with
      application of six polyacrylonitrile prosthetic cylinders in the inter-sphinteric
      space (Gate KeeperTM, THD, Correggio Italy). Follow up was at 3,6 and 12 months.
      RESULTS: Gate Keeper procedure required a short operative time; no morbidity or
      complications were experienced. Prolapse was successfully treated in all patients
      and the mean Vaizey's incontinence score value dropped from pre-operative 19.3 to
      9.3 after 3 months. All patients experienced a reduction of incontinence episodes
      and an improvement in daily activities and lifestyle. CONCLUSION: Gate Keeper
      implant is feasible and safe when associated to surgical procedures like
      Delorme's prolapse resection. Preliminary results are positive even if a study
      with a larger numbers of patients is needed to confirm the efficacy. A
      simultaneous treatment of faecal incontinence should be always considered when
      performing surgery for rectal prolapse. SHORT STATEMENT: The present manuscript
      describes a simultaneous combination of two surgical techniques to treat rectal
      prolapse and faecal incontinence. To date, there are no published data on a
      similar approach. The paper underlies the importance of treating faecal
      incontinence when performing surgery for rectal prolapse.

PMID- 25582298
TI  - A cost-minimization analysis in minimally invasive spine surgery using a national
      cost scale method.
AB  - INTRODUCTION: The last decade has seen the emergence of minimally invasive spine
      surgery. However, there is still no consensus on whether percutaneous
      osteosynthesis (PO) or open surgery (OS) is more cost-effective in treatment of
      traumatic fractures and degenerative lesions. The objective of this study is to
      compare the clinical results and hospitalization costs of OS and PO for
      degenerative lesions and thoraco-lumbar fractures. METHODS: This cost
      minimization study was performed in patients undergoing OS or PO on a 36-month
      period. Patient data, surgical and clinical results, as well as cost data were
      collected and analyzed. The financial costs were calculated based on diagnosis
      related group reimbursement and the French national cost scale, enabling the
      evaluation of charges for each hospital stay. RESULTS: 46 patients were included
      in this cost analysis, 24 patients underwent OS and 22 underwent PO. No
      significant difference was found between surgical groups in terms of patient's
      clinical features and outcomes during the patient hospitalization. The use of PO
      was significantly associated with a decrease in Length Of Stay (LOS). The cost
      minimization revealed that PO is associated with decreased hospital charges and
      shorten LOS for patients, with similar clinical outcomes and medical device cost
      to OS. CONCLUSIONS: This medico-economic study has leaded to choose
      preferentially the use of minimally invasive surgery techniques. This study also
      illustrates the discrepancy between the national health system reimbursement and
      real hospital charges. The medico-economic is becoming critical in the current
      context of sustainable health resource allocation.

PMID- 25582299
TI  - Injectate spread following ultrasound-guided lateral to medial approach for dual
      transversus abdominis plane blocks.
AB  - BACKGROUND: Bilateral dual transversus abdominis plane (BD-TAP) injections were
      devised to cover the T7-8 and L1 dermatomes, which are usually spared with
      classical and mid-axillary TAP injections. The purpose of this study was to
      delineate the vertical and lateral extent of injectate spread following a lateral
      to medial approach for TAP injections in embalmed cadavers. METHODS: Ultrasound
      guided subcostal and lateral TAP injections were performed on nine embalmed
      cadavers using 30 ml of 0.5% methylcellulose (20 ml for subcostal and 10 ml for
      lateral injections) with a 12-cm Tuohy needle in the first six cadavers (nine
      hemi-abdomens). Vertical extent and the medial to lateral extent of the dye
      spread were recorded after dissections of the abdominal wall. In a pilot of three
      cadavers not receiving TAP injections, anatomical impediments to proximal
      injectate spread were explored separately. RESULTS: The vertical spread of
      injectate was T7-L1 (n = 2/9), T8-L1 (n = 5/9) and T9-L1 (n = 2/9). None of the
      TAP injections extended beyond the mid-axillary line. No anatomical impediments
      for the flow of injectate to the T7 or T8 intercostal nerves were found at the
      level of the interdigitations of the transversus abdominis muscle and diaphragm.
      CONCLUSION: A lateral to medial approach for TAP injection resulted in spread of
      the injectate ranging from T7/8-L1 dermatomes in the majority of the hemi
      abdomens. Subcostal and lateral TAP injections do not cover the lateral cutaneous
      branches of the segmental nerves.

PMID- 25582295
TI  - ASICs as therapeutic targets for migraine.
AB  - Migraine is the most common neurological disorder and one of the most common
      chronic pain conditions. Despite its prevalence, the pathophysiology leading to
      migraine is poorly understood and the identification of new therapeutic targets
      has been slow. Several processes are currently thought to contribute to migraine
      including altered activity in the hypothalamus, cortical-spreading depression
      (CSD), and afferent sensory input from the cranial meninges. Decreased
      extracellular pH and subsequent activation of acid-sensing ion channels (ASICs)
      may contribute to each of these processes and may thus play a role in migraine
      pathophysiology. Although few studies have directly examined a role of ASICs in
      migraine, studies directly examining a connection have generated promising
      results including efficacy of ASIC blockers in both preclinical migraine models
      and in human migraine patients. The purpose of this review is to discuss the
      pathophysiology thought to contribute to migraine and findings that implicate
      decreased pH and/or ASICs in these events, as well as propose issues to be
      resolved in future studies of ASICs and migraine. This article is part of the
      Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'. 

PMID- 25582301
TI  - A new beginning ....

PMID- 25582300
TI  - Down-regulation of C/EBP homologous protein (CHOP) expression in gastric cardia
      adenocarcinoma: Their relationship with clinicopathological parameters and
      prognostic significance.
AB  - OBJECTIVE: C/EBP homologous protein (CHOP) is a multi-functional protein involved
      in the apoptosis pathway of endoplasmic reticulum stress (ERS) and is related to
      cancer progression. The purpose of this study was to assess CHOP expression as a
      prognostic biomarker in gastric cardia adenocarcinoma (GCA). METHODS: The levels
      of CHOP mRNA and protein in GCA and matched adjacent non-cancerous tissues were
      evaluated by quantitative real-time-polymerase chain reaction (qRT-PCR) and
      western blot. Furthermore, the CHOP protein expression and localization were
      examined by immunohistochemistry in GCA and corresponding adjacent non-cancerous
      tissues, gastritis and normal cardiac tissues. The association of CHOP expression
      with clinical pathological parameters and prognosis of GCA patients was
      statistically analyzed. RESULTS: Compared with adjacent non-cancerous tissues,
      the CHOP was down-regulated at mRNA and protein levels in GCA (P<0.01). In
      addition, immunohistochemistry analysis showed that CHOP positivity was lower in
      GCA than that in paired adjacent non-cancerous tissues, gastritis and normal
      tissues (P<0.01). CHOP expression rate gradually decreased with an increase in
      clinical stage, tumor differentiation and lymph node metastasis of GCA (P<0.05).
      Kaplan-Meier survival analysis revealed that low expression of CHOP correlated
      with poor prognosis of GCA patients. Moreover, univariate and multivariate
      analyses showed that CHOP was an independent prognostic marker for overall
      survival of GCA patients. CONCLUSIONS: Our results suggest that low CHOP
      expression predicts poor prognosis of GCA patients, and CHOP may be potentially a
      prognostic biomarker for GCA.

PMID- 25582302
TI  - Quantitative Relationships Between the Cytotoxicity of Flavonoids on the Human
      Breast Cancer Stem-Like Cells MCF7-SC and Their Structural Properties.
AB  - As some breast cancer-related deaths can be attributed to the metastasis of
      cancer stem cells, chemotherapeutic agents targeting breast cancer stem cells are
      of interest as a potential treatment. Flavonoids that exhibit cytotoxicity on
      breast cancer stem cells have rarely been observed. Thus, the objective of this
      study was to measure potential cytotoxic effects of 42 different flavonoids on
      the human breast cancer stem-like cell line, MCF7-SC. The relationship between
      flavonoid structural properties and cytotoxicity has not been reported
      previously; therefore, we determined quantitative structure-activity
      relationships using both comparative molecular field analysis and comparative
      molecular similarity analysis. Further biological experiments including Western
      blot analysis, flow cytometry, and immunofluorescence microscopy were also
      conducted on the most cytotoxic 8-chloroflavanone. 

PMID- 25582303
TI  - A genetically encoded Forster resonance energy transfer sensor for monitoring in
      vivo trehalose-6-phosphate dynamics.
AB  - Trehalose-6-phosphate is a pivotal regulator of sugar metabolism, growth, and
      osmotic equilibrium in bacteria, yeasts, and plants. To directly visualize the
      intracellular levels of intracellular trehalose-6-phosphate, we developed a
      series of specific Forster resonance energy transfer (FRET) sensors for in vivo
      microscopy. We demonstrated real-time monitoring of regulation in the trehalose
      pathway of Escherichia coli. In Saccharomyces cerevisiae, we could show that the
      concentration of free trehalose-6-phosphate during growth on glucose is in a
      range sufficient for inhibition of hexokinase. These findings support the
      hypothesis of trehalose-6-phosphate as the effector of a negative feedback
      system, similar to the inhibition of hexokinase by glucose-6-phosphate in
      mammalian cells and controlling glycolytic flux. 

PMID- 25582304
TI  - On the use of aptamer microarrays as a platform for the exploration of human
      prothrombin/thrombin conversion.
AB  - Microarrays are particular biosensors with multiple grafted probes that are
      generally used for parallel and simultaneous detection of various targets. In
      this study, we used microarrays with aptamer probes in order to follow up the
      different biomolecular interactions of a single enzyme, the thrombin protein,
      involved in the complex coagulation cascade. More precisely, thanks to label-free
      surface plasmon resonance imaging, we were able to monitor in real time an
      important step in the firing of the coagulation cascade in situ-the enzymatic
      transformation of prothrombin into thrombin, catalyzed by factor Xa. We were also
      able to appraise the influence of other biochemical factors and their
      corresponding inhibiting or enhancing behaviors on thrombin activation. Our study
      opens the door for the development of a complete microarray-based platform not
      only for the whole coagulation cascade analysis but also for novel drug screening
      assays in pharmacology. 

PMID- 25582306
TI  - Unusual alpha-synuclein and cerebellar pathologies in a case of hereditary
      myoclonus-dystonia without SGCE mutation.

PMID- 25582305
TI  - Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in
      patients with cancer in the esophagus or gastroesophageal junction - a
      prospective cohort pilot study within a randomized clinical trial.
AB  - BACKGROUND: Neoadjuvant therapy for cancer of the esophagus or gastroesophageal
      (GE)-junction is well established. The pros and cons of chemoradiotherapy and
      chemotherapy are debated. Chemoradiotherapy might impair cardiac function
      eliciting postoperative morbidity. The aim of this pilot study was to describe
      acute changes in left ventricular function following chemoradiotherapy or
      chemotherapy. METHODS: Patients with esophageal and (GE)-junction cancer enrolled
      at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy
      and chemotherapy were eligible. Patients were randomized to receive cisplatin and
      5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to
      surgery. Left ventricular function was evaluated using echocardiography and
      plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after
      neoadjuvant treatment. The primary outcome measure was left ventricular global
      strain (GS). Clinical effects were assessed using repeated exercise tests. Linear
      mixed models were used to analyze the effects of treatment group, and the
      interaction between groups. RESULTS: 40 patients participated (chemoradiotherapy,
      n=17; chemotherapy, n=23). In the chemoradiotherapy group there was no change in
      left ventricular global strain but mitral annular plane systolic excursion
      (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity),
      and the ratio of early to late ventricular filling velocities (E/A ratio)
      decreased significantly (p=0.02, p=0.01, and p=0.03, respectively). No changes
      were observed in the chemotherapy group. There was a trend towards an interaction
      effect for MAPSE sept and E (p=0.09 and p=0.09). NT-proBNP increased following
      chemoradiotherapy (p=0.05) but not after chemotherapy (p>0.99), and there was a
      trend towards an interaction effect (p=0.07). Working capacity decreased
      following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy
      p=0.03) and was more pronounced after chemoradiotherapy with a trend towards an
      interaction effect (p=0.10). CONCLUSIONS: Neoadjuvant chemoradiotherapy but not
      chemotherapy before surgery for cancer of the esophagus or GE-junction seems to
      induce an acute negative effect on both systolic and diastolic left ventricular
      function. Future studies on neoadjuvant treatment for esophageal cancer are
      suggested to add measurements of cardiac function. TRIAL REGISTRATION: Clinical
      Trials.gov NCT01362127 .

PMID- 25582307
TI  - Advances in computationally modeling human oral bioavailability.
AB  - Although significant progress has been made in experimental high throughput
      screening (HTS) of ADME (absorption, distribution, metabolism, excretion) and
      pharmacokinetic properties, the ADME and Toxicity (ADME-Tox) in silico modeling
      is still indispensable in drug discovery as it can guide us to wisely select drug
      candidates prior to expensive ADME screenings and clinical trials. Compared to
      other ADME-Tox properties, human oral bioavailability (HOBA) is particularly
      important but extremely difficult to predict. In this paper, the advances in
      human oral bioavailability modeling will be reviewed. Moreover, our deep insight
      on how to construct more accurate and reliable HOBA QSAR and classification
      models will also discussed. 

PMID- 25582308
TI  - Insecticide resistance status in Culex quinquefasciatus in Benin.
AB  - BACKGROUND: Culex quinquefasciatus, an arboviral and filarial vector, is present
      year round in several cities of the Republic of Benin. There is more information
      on the resistance status to malaria vectors compared to Culicines. It is
      therefore unfortunate that the international focus is on Anopheles control and
      not so much done against Cx. quinquefasciatus, a rather more resilient mosquito
      to many insecticides that deserves attention. The present study aims to assess
      the resistance status of Cx. quinquefasciatus to carbamates, pyrethroids and
      organochlorine and discuss the implications for vector control in four
      contrasting localities of the country. METHODS: Four contrasting localities of
      the country were selected for mosquito collection during the dry season based on
      their variation in agricultural production, use of insecticides and/or ecological
      settings. Bioassay were performed on adults collected from the field to assess
      the susceptibility of Cx. quinquefasciatus to insecticide-impregnated papers
      (permethrin 0.75%, delthamethrin 0.05%, DDT 4%, and bendiocarb 0.1%) following
      WHOPES guidelines. Molecular assays were carried out to detect the presence of
      knock down resistance (kdr) and acetylcholinesterase (ace. 1) mutations in
      surviving specimens using PCR techniques. RESULTS: WHO diagnostic tests showed
      high frequency of resistance in Cx. quinquefasciatus to permethrin (ranging from
      4 to 24% mortality), deltamethrin (24 to 48%), DDT (4 to 12%) and bendiocarb (60
      to 76%) in the four selected areas. This was consistent with the presence of
      target site insensitivity due to kdr and ace.1 mutations, which were
      significantly higher in areas where farmers used insecticides for pests control
      than in areas where no insecticides were used (p < 0.05.). CONCLUSION: These
      findings showed that wild populations of Cx. quinquefasciatus have developed
      resistance against pyrethroids, organochlorine and carbamate. This situation of
      resistance may seriously jeopardize the efficacy of Insecticide Residual Spray
      (IRS) and Long-Lasting Insecticide nets (LLINs) on which, most African countries
      including Benin, rely to reduce malaria transmission.

PMID- 25582309
TI  - Effect of daily supplementation with iron and zinc on iron status of childbearing
      age women.
AB  - The objective was to determine the effect of daily supplementation with 30 mg of
      iron (Fe) plus 30 mg of zinc (Zn) for 3 months on Fe status of women of
      childbearing age. This was a randomized double-blind, placebo-controlled trial.
      Eighty-one women (18-45 years) were randomly assigned to receive either a daily
      single dose of 30 mg of Fe (group 1; n = 28) and 30 mg of Fe plus 30 mg of Zn
      (group 2; n = 26) or placebo (n = 27) for 3 months. Hemoglobin (Hb), mean
      corpuscular volume, serum Fe, total iron-binding capacity, transferrin
      saturation, erythrocyte Zn protoporphyrin, serum ferritin (SF), serum transferrin
      receptor (TfR), total body Fe, serum Zn, and high-sensitivity C-reactive protein
      were measured at baseline and at the end of the study. At baseline, 3.7, 28.4,
      and 3.7 % of women had iron-deficiency anemia (IDA), Fe deficiency without
      anemia, and depleted Fe stores, respectively. No significant differences on Fe
      status were found between groups before supplementation. After supplementation,
      group 2 showed a significant increase of Hb and total body Fe and a significant
      decrease of TfR compared with placebo (p < 0.05). Moreover, serum Zn increased
      significantly in group 2 compared with group 1 (p < 0.01) and placebo (p < 0.01).
      In conclusion, daily supplementation with 30 mg of Fe plus 30 mg of Zn for 3
      months improved significantly the Fe and Zn status of women, compared with those
      who received placebo. The positive effect of Fe supplementation on Fe status is
      enhanced by combined Zn supplementation.

PMID- 25582310
TI  - A comparison of the outcome using LigasureTM small jaw and clamp-and-tie
      technique in thyroidectomy: a randomized single center study.
AB  - PURPOSE: Hypoparathyroidism and paralysis of the recurrent laryngeal nerve (RLN)
      still remain the most frequent specific complications of thyroid surgery. This
      study evaluates the effects of employment of a recently introduced device
      (LigaSureTM Small Jaw, LSJ), compared to the traditional clamp-and-tie (CT)
      technique, on the short- and long-term outcome of the patients who underwent
      thyroidectomy. METHODS: This prospective, randomized study included 190 patients
      enrolled from October 2011 to July 2013. The numbers of patients in the LSJ group
      and the CT group were both 95. We studied the following: operative times,
      intraoperative and postoperative blood losses, intact parathormone (iPTH) and
      calcium serum levels, and the incidence of RLN paralysis. RESULTS: The two
      cohorts were homogeneous for age, sex, surgical indication, BMI, ASA score, and
      estimated thyroid volume. Operation time has been 73.90 +/- 23.35 min in group CT
      and 60.20 +/- 22.36 min in group LSJ (p = 0.002). Intraoperative blood losses
      have been 47 +/- 18 ml in group CT and 38 +/- 14 in group LSJ (p = 0.002), while
      postoperative blood losses have been 45 +/- 21 ml in group CT and 40 +/- 20 in
      group LSJ (p = 0.105). The mean calcium blood level in group CT has been 8.12,
      7.79, and 7.92 mg/dl in the first, second, and third postoperative days,
      respectively, as well as 8.26, 7.97, and 8.22 mg/dl for group LSJ (p > 0.05).
      Basal and post-thyroidectomy iPTH levels have been 46.49 and 23.64 pg/ml in group
      CT (Delta = 49.15 %), as well as 51.06 and 27.73 (Delta = 45.69 %) in group LSJ
      (p > 0.05). Permanent RLN paralysis was 1.05 % in LSJ group and 0 % in CT group.
      CONCLUSION: The employment of LSJ reduces in a statistically significant way both
      operative times and intraoperative blood losses. No significant differences were
      found as far as postoperative RLN paralysis and hypoparathyroidism.

PMID- 25582312
TI  - Ensuring an equal playing field for antigen receptor loci variable regions.

PMID- 25582311
TI  - Volumetric femoral BMD, bone geometry, and serum sclerostin levels differ between
      type 2 diabetic postmenopausal women with and without fragility fractures.
AB  - While type 2 diabetes (T2D) is associated with higher skeletal fragility,
      specific risk stratification remains incompletely understood. We found volumetric
      bone mineral density, geometry, and serum sclerostin differences between low
      fracture risk and high-fracture risk T2D women. These features might help
      identify T2D individuals at high fracture risk in the future. INTRODUCTION:
      Diabetic bone disease, an increasingly recognized complication of type 2 diabetes
      mellitus (T2D), is associated with high skeletal fragility. Exactly which T2D
      individuals are at higher risk for fracture, however, remains incompletely
      understood. Here, we analyzed volumetric bone mineral density (vBMD), geometry,
      and serum sclerostin levels in two specific T2D subsets with different fracture
      risk profiles. We examined a T2D group with prior history of fragility fractures
      (DMFx, assigned high-risk group) and a fracture-free T2D group (DM, assigned low
      risk group) and compared their results to nondiabetic controls with (Fx) and
      without fragility fractures (Co). METHODS: Eighty postmenopausal women (n = 20
      per group) underwent quantitative computed tomography (QCT) to compute vBMD and
      bone geometry of the proximal femur. Additionally, serum sclerostin, vitamin D,
      parathyroid hormone (PTH), HbA1c, and glomerular filtration rate (GFR) levels
      were measured. Statistical analyses employed linear regression models. RESULTS:
      DMFx subjects exhibited up to 33 % lower femoral neck vBMD than DM subjects
      across all femoral sites (-19 % <= DeltavBMD <= -33 %, 0.008 <= p <=0.021).
      Additionally, DMFx subjects showed significantly thinner cortices (-6 %, p =
      0.046) and a trend toward larger bone volume (+10 %, p = 0.055) relative to DM
      women and higher serum sclerostin levels when compared to DM (+31.4 %, p =
      0.013), Fx (+25.2 %, p = 0.033), and control (+22.4 %, p = 0.028) subjects.
      CONCLUSION: Our data suggest that volumetric bone parameters by QCT and serum
      sclerostin levels can identify T2D individuals at high risk of fracture and might
      therefore show promise as clinical tools for fracture risk assessment in T2D.
      However, future research is needed to establish diabetes-specific QCT- and
      sclerostin-reference databases.

PMID- 25582313
TI  - Re-tuning bone formation.

PMID- 25582314
TI  - Pointing B cells in the right direction.

PMID- 25582315
TI  - Reporting accuracy of population dietary sodium intake using duplicate 24 h
      dietary recalls and a salt questionnaire.
AB  - High dietary Na intake is associated with multiple health risks, making accurate
      assessment of population dietary Na intake critical. In the present study,
      reporting accuracy of dietary Na intake was evaluated by 24 h urinary Na
      excretion using the EPIC-Soft 24 h dietary recall (24-HDR). Participants from a
      subsample of the European Food Consumption Validation study (n 365; countries:
      Belgium, Norway and Czech Republic), aged 45-65 years, completed two 24 h urine
      collections and two 24-HDR. Reporting accuracy was calculated as the ratio of
      reported Na intake to that estimated from the urinary biomarker. A questionnaire
      on salt use was completed in order to assess the discretionary use of table and
      cooking salt. The reporting accuracy of dietary Na intake was assessed using two
      scenarios: (1) a salt adjustment procedure using data from the salt
      questionnaire; (2) without salt adjustment. Overall, reporting accuracy improved
      when data from the salt questionnaire were included. The mean reporting accuracy
      was 0.67 (95 % CI 0.62, 0.72), 0.73 (95 % CI 0.68, 0.79) and 0.79 (95 % CI 0.74,
      0.85) for Belgium, Norway and Czech Republic, respectively. Reporting accuracy
      decreased with increasing BMI among male subjects in all the three countries. For
      women from Belgium and Norway, reporting accuracy was highest among those
      classified as obese (BMI >= 30 kg/m2: 0.73, 95 % CI 0.67, 0.81 and 0.81, 95 % CI
      0.77, 0.86, respectively). The findings from the present study showed
      considerable underestimation of dietary Na intake assessed using two 24-HDR. The
      questionnaire-based salt adjustment procedure improved reporting accuracy by 7-13
      %. Further development of both the questionnaire and EPIC-Soft databases (e.g.
      inclusion of a facet to describe salt content) is necessary to estimate
      population dietary Na intakes accurately. 

PMID- 25582316
TI  - Distinct prognostic values of ALDH1 isoenzymes in breast cancer.
AB  - Aldehyde dehydrogenase 1 (ALDH1), also known as aldehyde dehydrogenase 1 family,
      is composed of six enzymes that are expressed at high levels in stem cells and
      are involved in the regulation of stem cell function. Increased ALDH1 activity
      has been found in the stem cell populations of leukemia and some solid tumors
      including breast cancer (BC). However, which ALDH1's isoenzymes are contributing
      to ALDH1 activity has not been determined. In addition, the prognostic value of
      individual ALDH1 isoenzyme is not clear. In the current study, we investigated
      the prognostic value of ALDH1 isoenzymes in BC patients through "the Kaplan-Meier
      plotter" (KM plotter) database, in which updated gene expression data and
      survival information are from a total of 3455 BC patients. ALDH1A1 messenger RNA
      (mRNA) high expression was found to be correlated to worsen overall survival (OS)
      for all BC patients. ALDH1A2 and ALDH1L1 mRNA high expressions were found to be
      correlated to better OS for all BC patients. Both of ALDH1A3 and ALDH1B1 mRNA
      high expressions were not found to be correlated to OS for all BC patients. These
      results strongly support that ALDH1A1 was only a biomarker for predicting poor
      survival of BC patients among ALDH1 isoenzymes. ALDH1A1 might be a major
      contributor of ALDH1 activity in BC, since only ALDH1A1 mRNA high expression was
      found to be significantly correlated to worsen OS for all BC patients. 

PMID- 25582317
TI  - CLIC1 a novel biomarker of intraperitoneal metastasis in serous epithelial
      ovarian cancer.
AB  - Early diagnosis of intraperitoneal metastasis is a pivot for survival of patients
      with serous epithelial ovarian cancers (SEOC). However, to date, there is lack of
      efficient molecular biomarker for early metastasis of SEOC. Here, we found that
      the expression of chloride intracellular channel 1 (CLIC1) is highly correlative
      with intraperitoneal metastasis. There is very low expression of CLIC1 in normal
      ovaries (NO), benign ovarian tumor (BOT), and primary ovarian cancer without
      metastasis (POCNM); but its expression is remarkably high in primary ovarian
      cancer with metastasis (POCM) omentum and peritoneal metastasis. Furthermore, for
      clinic prediction of intraperitoneal metastasis of SEOC, the sensitivity and
      specificity of CLIC1 overexpression were 97.4 and 88.1 %, respectively.
      Collectively, CLIC1 may be a potential sensitive and specific molecular biomarker
      for early diagnose for SEOC metastasis.

PMID- 25582319
TI  - Prediction of protein-DNA complex mobility in gel-free capillary electrophoresis.
AB  - Selection of protein binders from highly diverse combinatorial libraries of DNA
      encoded small molecules is a highly promising approach for discovery of small
      molecule drug leads. Methods of kinetic capillary electrophoresis provide the
      high efficiency of partitioning required for such selection but require the
      knowledge of electrophoretic mobility of the protein-ligand complex. Here we
      present a theoretical approach for an accurate estimate of the electrophoretic
      mobility of such complexes. The model is based on a theory of the thin double
      layer and corresponding expressions used for the mobilities of a rod-like short
      oligonucleotide and a sphere-like globular protein. The model uses empirical
      values of mobilities of free protein, free ligand, and electroosmotic flow. The
      model was tested with a streptavidin-dsDNA complex linked through biotin (small
      molecule). The deviation of the prediction from the experimental mobility did not
      exceed 4%, thus confirming that not only is the model adequate but it is also
      accurate. This model will facilitate reliable use of KCE methods for selection of
      drug leads from libraries of DNA-encoded small molecules. 

PMID- 25582318
TI  - XRCC1 R399Q polymorphism and colorectal cancer risk in the Chinese Han
      population: a meta-analysis.
AB  - X-ray repair cross-complementing group 1 (XRCC1) plays a key role in DNA repair,
      genetic instability, and tumorigenesis. The XRCC1 R399Q polymorphism has been
      reported in some studies to influence the risk of colorectal cancer (CRC), though
      this remains controversial. We performed a meta-analysis to determine the
      association of XRCC1 R399Q polymorphisms with CRC risk in the Chinese Han
      population. A literature search was conducted using PubMed, EMBASE, and the China
      National Knowledge Infrastructure to identify eligible studies published before
      June 2014. The pooled odds ratio (OR) and corresponding 95% confidence interval
      (CI) were used to estimate the effect of XRCC1 R399Q polymorphisms on CRC risk.
      Eleven case-control studies with a total of 3194 CRC cases and 4472 controls were
      identified. No significant association between the XRCC1 R399Q polymorphism and
      CRC risk was observed in the Chinese Han population (Gln/Gln vs. Arg/Arg, OR =
      1.26, 95% CI = 0.85-1.87, P OR = 0.242; Arg/Gln vs. Arg/Arg, OR = 0.95, 95% CI =
      0.70-1.18, P OR = 0.651; dominant model, OR = 1.09, 95% CI = 0.86-1.38, P OR =
      0.480; and recessive model, OR = 1.24, 95% CI = 0.91-1.70, P OR = 0.177). After
      excluding two studies that deviated from the Hardy-Weinberg equilibrium, there
      remained no significant association between XRCC1 R399Q and CRC risk. No
      publication bias was found using the funnel plot and Egger's test. Our meta
      analysis results suggest that the XRCC1 R399Q polymorphism is not associated with
      increased risk of CRC in the Chinese Han population.

PMID- 25582320
TI  - Young Adolescents' Body Dysmorphic Symptoms: Associations with Same- and Cross
      Sex Peer Teasing via Appearance-based Rejection Sensitivity.
AB  - In this study of young adolescents' (N = 188, M age  = 11.93, 54.8% females) body
      dysmorphic disorder (BDD) symptoms, we examined a theoretically-derived model to
      determine if symptoms could be explained by appearance-related teasing, general
      peer victimization, and social anxiety. BDD symptoms were assessed as distressing
      preoccupation with perceived appearance defects, social avoidance, and repeated
      grooming and appearance checking. Associations were expected to occur via the
      social-perceptual bias known as appearance-based rejection sensitivity
      (appearance-RS). The source of appearance teasing was also considered (same-sex
      vs. cross-sex peers), and age and gender moderation were assessed. As predicted,
      in a structural equation model, BDD symptoms were higher when adolescents self
      reported more appearance teasing and higher social anxiety. Moreover, it was
      appearance teasing by cross-sex peers, rather than same-sex peers, that was
      uniquely associated with elevated BDD symptoms. These associations were partially
      mediated by appearance-RS. Notably, peer-reported general victimization was not
      associated with BDD symptoms. There was no evidence for gender moderation, but
      some age moderation was found, with stronger associations usually found among
      older compared to younger adolescents. The findings suggest that appearance
      related social adversity, particularly cross-sex teasing, is linked with greater
      concerns about rejection due to appearance and, in turn, heightened BDD symptoms.
      This has important implications for understanding the development and treatment
      of BDD. Continued research to identify the social experiences and interpretative
      biases that contribute to BDD symptomology is needed.

PMID- 25582321
TI  - Synthesis of prostaglandin analogues, latanoprost and bimatoprost, using
      organocatalysis via a key bicyclic enal intermediate.
AB  - Two antiglaucoma drugs, bimatoprost and latanoprost, which are analogues of the
      prostaglandin, PGF2alpha, have been synthesized in just 7 and 8 steps,
      respectively. The syntheses employ an organocatalytic aldol reaction that
      converts succinaldehyde into a key bicyclic enal intermediate, which is primed
      for attachment of the required lower and upper side chains. By utilizing the
      crystalline lactone, the drug molecules were prepared in >99% ee. 

PMID- 25582322
TI  - Hypothalamic differences in expression of genes involved in monoamine synthesis
      and signaling pathways after insulin injection in chickens from lines selected
      for high and low body weight.
AB  - Long-term selection for juvenile body weight from a common founder population
      resulted in two divergent chicken lines (low-weight selected line (LWS), high
      weight selected line (HWS)) that display distinct food intake and blood glucose
      responses to exogenous neuropeptides and insulin. The objective of this study was
      to elucidate putative targets affecting food intake and energy homeostasis by
      sequencing hypothalamic RNA from LWS and HWS chickens after insulin injection.
      Ninety-day-old female LWS and HWS chickens were injected with either vehicle or
      insulin and hypothalamus collected at 1 h postinjection. Through RNA sequencing,
      a total of 361 differentially expressed genes (DEGs) were identified. There was
      greater expression of genes, mainly tyrosine hydroxylase (TH), L-aromatic amino
      acid decarboxylase (DDC), and vesicular monoamine transporter (VMAT), involved in
      serotonin and dopamine biosynthesis and signaling in LWS than in HWS vehicle
      injected chickens. In contrast, after insulin injection, these genes were more
      highly expressed in HWS than in LWS. We identified 90 single nucleotide
      polymorphisms (SNPs) existing only in the HWS and 121 SNPs specific to LWS and
      5119 SNPs close to fixation (with absolute frequency difference >=0.9). Four were
      located in genes encoding enzymes associated with serotonergic and dopaminergic
      pathways, such as DDC, TH, and solute carrier family 18, member 2 (VMAT). These
      data implicate differences in biogenic amines such as serotonin and dopamine in
      hypothalamic physiology between the chicken lines, and these differences might be
      associated with polymorphisms during long-term selection. Changes in serotonergic
      and dopaminergic signaling pathways in response to insulin injection suggest a
      role in whole-body energy homeostasis. 

PMID- 25582323
TI  - Purification of Helicobacter suis Strains From Biphasic Cultures by Single Colony
      Isolation: Influence on Strain Characteristics.
AB  - BACKGROUND: Helicobacter (H.) suis causes gastritis and decreased weight gain in
      pigs. It is also the most prevalent non-Helicobacter pylori Helicobacter species
      in humans with gastric disease. H. suis is extremely fastidious, and so far,
      biphasic culture conditions were essential for isolation and culture, making it
      impossible to obtain single colonies. Hence, cultures obtained from an individual
      animal may contain multiple H. suis strains, which is undesirable for experiments
      aiming for instance at investigating H. suis strain differences. MATERIALS AND
      METHODS: Pure cultures of H. suis were established by growing bacteria as
      colonies on 1% brucella agar plates, followed by purification and enrichment by
      biphasic subculture. Characteristics of these single colony-derived strains were
      compared with those of their parent strains using multilocus sequence typing
      (MLST) and by studying bacterium-host interactions using a gastric epithelial
      cell line and Mongolian gerbil model. RESULTS: The purification/enrichment
      procedure required a nonstop culture of several weeks. For 4 of 17 H. suis
      strains, MLST revealed differences between parental and single colony-derived
      strains. For three of four single colony-derived strains tested, the cell death
      inducing capacity was higher than for the parental strain. One single colony
      derived strain lost its capacity to colonize Mongolian gerbils. For the four
      other strains tested, colonization capacity and histopathologic changes were
      similar to what has been described when using strains with only a history of
      limited biphasic culture. CONCLUSIONS: A method was developed to obtain single
      colony-derived H. suis strains, but this procedure may affect the bacterial
      genotype and phenotype.

PMID- 25582326
TI  - Behavioral profiles in frontal lobe epilepsy: Autobiographic memory versus mood
      impairment.
AB  - OBJECTIVES: Autobiographic memory encompasses the encoding and retrieval of
      episodes, people, and places encountered in everyday life. It can be impaired in
      both epilepsy and frontal lobe damage. Here, we performed an initial
      investigation of how autobiographic memory is impacted by chronic frontal lobe
      epilepsy (FLE) together with its underlying pathology. METHOD: We prospectively
      studied a series of nine consecutive patients with medically refractory FLE,
      relative to 24 matched healthy controls. Seven of the nine patients had frontal
      lobe structural abnormalities. Episodic and semantic autobiographic memory
      functioning was profiled, and factors associated with impaired autobiographic
      memory were identified among epileptologic, neuroimaging, neuropsychiatric, and
      cognitive variables including auditory-verbal and visual memory, and the
      executive function of cognitive control. RESULTS: Results showed that the FLE
      group experienced significantly higher rates of autobiographic memory and mood
      disturbance (p < 0.001), with detailed assessment of individual patients
      revealing two profiles of impairment, primarily characterized by cognitive or
      mood disturbance. Five of the patients (56%) exhibited significant episodic
      autobiographic memory deficits, whereas in three of these, knowledge of semantic
      autobiographic facts was preserved. Four of them also had reduced cognitive
      control. Mood disorder was largely unrelated to poor autobiographic memory. In
      contrast, the four cases with preserved autobiographic memory were notable for
      their past or current depressive symptoms. SIGNIFICANCE: These findings provide
      preliminary data that frontal lobe seizure activity with its underlying pathology
      may selectively disrupt large-scale cognitive or affective networks, giving rise
      to different neurobehavioral profiles that may be used to inform clinical
      management.

PMID- 25582327
TI  - Metallohelices: potential mimetics of alpha-helical peptides in cancer treatment?

PMID- 25582324
TI  - Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients
      Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria.
AB  - Studying the genetic diversity and natural polymorphisms of HIV-1 would benefit
      our understanding of HIV drug resistance (HIVDR) development and predict
      treatment outcomes. In this study, we have characterized the HIV-1 genetic
      diversity and natural polymorphisms at the 5' region of the pol gene encompassing
      the protease (PR) and reverse transcriptase (RT) from 271 plasma specimens
      collected in 2008 from HIV-1-infected patients who were eligible for initiating
      antiretroviral therapy in Abuja (Nigeria). The analysis indicated that the
      predominant subtype was subtype G (31.0%), followed by CRF02-AG (19.2 %), CRF43
      02G (18.5%), and A/CRF36-cpx (11.4%); the remaining (19.9%) were other subtypes
      and circulating (CRF) and unique (URF) recombinant forms. Recombinant viruses
      (68.6%) were the major viral strains in the region. Eighty-four subtype G
      sequences were further mainly classified into two major and two minor clusters;
      sequences in the two major clusters were closely related to the HIV-1 strains in
      two of the three major subtype G clusters detected worldwide. Those in the two
      minor clusters appear to be new subtype G strains circulating only in Abuja. The
      pretreatment DR prevalence was <3%; however, numerous natural polymorphisms were
      present. Eleven polymorphic mutations (G16E, K20I, L23P, E35D, M36I, N37D/S/T,
      R57K, L63P, and V82I) were detected in the PR that were subtype or CRF specific
      while only three mutations (D123N, I135T, and I135V) were identified in the RT.
      Overall, this study indicates an evolving HIV-1 epidemic in Abuja with
      recombinant viruses becoming the dominant strains and the emergence of new
      subtype G strains; pretreatment HIVDR was low and the occurrence of natural
      polymorphism in the PR region was subtype or CRF dependent. 

PMID- 25582325
TI  - Glyceraldehyde-derived pyridinium (GLAP) evokes oxidative stress and inflammatory
      and thrombogenic reactions in endothelial cells via the interaction with RAGE.
AB  - BACKGROUND: We have previously shown that serum levels of glyceraldehyde-derived
      advanced glycation end products (Gly-AGEs) are elevated under oxidative stress
      and/or diabetic conditions and associated with insulin resistance, endothelial
      dysfunction and vascular inflammation in humans. Further, Gly-AGEs not only evoke
      oxidative and inflammatory reactions in endothelial cells (ECs) through the
      interaction with a receptor for AGEs (RAGE), but also mimic vasopermeability
      effects of AGE-rich serum purified from diabetic patients on hemodialysis. These
      observations suggest that Gly-AGE-RAGE system might be a therapeutic target for
      vascular complications in diabetes. However, since incubation of glyceraldehyde
      with proteins will generate a large number of structurally distinct AGEs, it
      remains unclear what type of AGE structures could mediate the deleterious effects
      of Gly-AGEs on ECs. AIMS AND METHODS: Therefore, in this study, we examined (1)
      whether glyceraldehyde-derived pyridinium (GLAP), one of the Gly-AGEs generated
      by the incubation of lysine with glyceraldehyde, elicited reactive oxygen species
      (ROS) generation and inflammatory and thrombogenic gene expression in human
      umbilical vein ECs (HUVECs) via the interaction with RAGE and (2) if DNA aptamers
      raised against Gly-AGEs or GLAP (AGE-aptamer or GLAP-aptamer) inhibited the
      binding of GLAP to RAGE and subsequently suppressed the harmful effects of GLAP
      on HUVECs. RESULTS: GLAP stimulated ROS generation in a bell-shaped manner; GLAP
      at 10 MUg/ml increased ROS generation in HUVECs by 40%, which was blocked by the
      treatment with RAGE-antibody (RAGE-Ab). Ten MUg/ml GLAP significantly up
      regulated mRNA levels of RAGE, monocyte chemoattractant protein-1, intercellular
      adhesion molecule-1, vascular cell adhesion molecule-1 and plasminogen activator
      inhibitor-1 in HUVECs, which were also suppressed by RAGE-Ab. AGE-aptamer or GLAP
      aptamer significantly blocked these deleterious effects of GLAP on HUVECs.
      Moreover, quartz crystal microbalance analyses revealed that GLAP actually bound
      to RAGE and that AGE-aptamer or GLAP-aptamer inhibited the binding of GLAP to
      RAGE. CONCLUSIONS: The present study suggests that GLAP might be a main
      glyceraldehyde-related AGE structure in Gly-AGEs that bound to RAGE and
      subsequently elicited ROS generation and inflammatory and thrombogenic reactions
      in HUVECs. Blockade of the GLAP-RAGE interaction by AGE-aptamer or GLAP-aptamer
      might be a novel therapeutic strategy for preventing vascular injury in diabetes.

PMID- 25582328
TI  - p21-activated kinase 4: a druggable target in the elusive oncogenic KRAS pathway?

PMID- 25582329
TI  - Retrofitting the battlements: tight junction remodeling as a novel antimicrobial
      approach.

PMID- 25582330
TI  - Donepezil-ferulic acid hybrids as anti-Alzheimer drugs.
AB  - BACKGROUND: Due to the complex nature of Alzheimer's disease, there is a renewed
      and growing search for multitarget drugs. RESULTS: Donepezil-ferulic acid hybrids
      (DFAHs) were prepared by the one-pot Ugi-4CR in low-to-moderate yields. DFAHs are
      potent antioxidant agents, showing oxygen radical absorbance capacity values in
      the range 4.80-8.71 trolox equivalents, quite higher compared with those recorded
      for ferulic acid and melatonin. From the ChEs inhibition studies, we conclude
      that DFAH 8, bearing an ethylene linker, and DFAH 12, bearing a propylene linker,
      both substituted with a melatonin motif, are the most potent inhibitors, in the
      nanomolar range. CONCLUSION: We have identified DFAH 8 as a very potent
      antioxidant, and totally selective equineButyrylCholinEsterase (eqBuChE)
      inhibitor.

PMID- 25582331
TI  - TAK1 selective inhibition: state of the art and future opportunities.
AB  - The mitogen activated protein kinase kinase kinase transforming growth factor
      beta-activated kinase 1 (TAK1) has emerged as an interesting therapeutic target
      for inflammatory diseases and cancer. TAK1 is a tightly regulated kinase that
      represents a key signaling node in cellular responses to inflammatory stimuli,
      modulating both expression of inflammatory mediators and cell death. The first
      inhibitors described for TAK1 exploit the active site cysteine residue found in
      this kinase, but more recently both type I ATP hinge-binding inhibitors and type
      II DFG-out inhibitors have been described. This article will review the emerging
      role of TAK1 kinase in inflammation, the current state of the art for small
      molecule inhibitor development and opportunities for chemical biology approaches.

PMID- 25582332
TI  - Targeting Pim kinases for cancer treatment: opportunities and challenges.
AB  - Pim oncogenes are highly expressed in many types of hematological and solid
      cancers. Pim kinases regulate the network of signaling pathways that are critical
      for tumorigenesis and development, making Pim kinases the attractive drug
      targets. Currently, two approaches have been employed in designing Pim kinase
      inhibitors: ATP-mimetics and non-ATP mimetics; but all target the ATP-binding
      pocket and are ATP-competitive. In this review, we summarize the current progress
      in understanding the Pim-related structure and biology, and provide insights into
      the binding modes of some prototypical Pim-1 inhibitors. The challenges as well
      as opportunities are highlighted for development of Pim kinase inhibitors as
      potential anticancer agents. 

PMID- 25582334
TI  - Neuroprotection, Plasticity Manipulation, and Regenerative Strategies to Improve
      Cardiovascular Function following Spinal Cord Injury.
AB  - Damage to the central nervous system, as in the case of spinal cord injury (SCI),
      results in disrupted supraspinal sympathetic influence and subsequent
      cardiovascular control impairments. Consequently, people with SCI suffer from
      disordered basal hemodynamics and devastating fluctuations in blood pressure, as
      in the case of autonomic dysreflexia (AD), which likely contribute to this
      population's leading cause of mortality: cardiovascular disease. The development
      of AD is related, at least in part, to neuroanatomical changes that include
      disrupted descending supraspinal sympathetic control, changes in propriospinal
      circuitry, and inappropriate afferent sprouting in the dorsal horn. These
      anatomical mechanisms may thus be targeted by neural regenerative and protective
      therapies to improve cardiovascular control and reduce AD. Here, we discuss the
      relationship between abnormal cardiovascular control and its underlying
      neuroanatomy. We then review current studies investigating biochemical strategies
      to reduce the severity of AD through: 1) reducing aberrant calcitonin gene
      related peptide immunoreactive afferent sprouting; 2) inhibiting inflammatory
      processes; and 3) re-establishing descending supraspinal sympathetic control.
      Finally, we discuss why additional biochemical agents and combinational
      approaches may be needed to completely ameliorate this condition. 

PMID- 25582333
TI  - Brain motor control assessment of upper limb function in patients with spinal
      cord injury.
AB  - BACKGROUND: The brain motor control assessment (BMCA) for the upper limb has been
      developed to add resolution to the clinical evaluation in patients with spinal
      cord injury (SCI). BMCA is a surface electromyography (sEMG)-based measure of
      motor output from the central nervous system during a variety of reflex and
      voluntary motor tasks performed under strictly controlled conditions. METHOD:
      Nine participants were recruited and assessed four times over a period of 1 year
      in a prospective cohort study design. The sEMG of 15 muscles (7 muscles from each
      upper limb and rectus abdominis) were recorded throughout the following stages of
      the BMCA protocol: (i) relaxation, (ii) reinforcement maneuvers, (iii) voluntary
      tasks, (iv) tendon-tap reflex responses, (v) vibration responses. RESULTS:
      Similarity index (SI) values were significantly lower in the SCI group for
      unilateral shoulder abduction (P = 0.006) and adduction (P = 0.021), elbow
      extension (P = 0.038), wrist flexion/extension with palm up (P < 0.001; P <
      0.001) and wrist flexion with palm down (P = 0.016). sEMG magnitudes were also
      significantly lower in the SCI group for wrist flexion/extension with palm up (P
      < 0.001; P = 0.042). SI changes over time were significant for tasks related to
      wrist joint (P = 0.002). CONCLUSION: Clinicians who are involved in
      rehabilitation of patients with SCI can use the BMCA to assess their patients'
      motor control abilities and monitor their progression throughout their
      rehabilitation process. The results of this type of neurophysiological assessment
      might be useful to tailor therapeutic strategies for each patient.

PMID- 25582335
TI  - Large animal evaluation of riboflavin and ultraviolet light-treated whole blood
      transfusion in a diffuse, nonsurgical bleeding porcine model.
AB  - BACKGROUND: The Mirasol system has been demonstrated to effectively inactivate
      white blood cells (WBCs) and reduce pathogens in whole blood in vitro. The
      purpose of this study was to compare the safety and efficacy of Mirasol-treated
      fresh whole blood (FWB) to untreated FWB in an in vivo model of surgical
      bleeding. STUDY DESIGN AND METHODS: A total of 18 anesthetized pigs (40 kg)
      underwent a 35% total blood volume bleed, cooling to 33 degrees C, and a
      standardized liver injury. Animals were then randomly assigned to resuscitation
      with either Mirasol-treated or untreated FWB, and intraoperative blood loss was
      measured. After abdominal closure, the animals were observed for 14 days, after
      which the animals were euthanized and tissues were obtained for histopathologic
      examination. Mortality, tissue near-infrared spectroscopy, red blood cell (RBC)
      variables, platelets (PLTs), WBCs, and coagulation indices were analyzed.
      RESULTS: Total intraoperative blood loss was similar in test and control arms
      (8.3 +/- 3.2 mL/kg vs. 7.7 +/- 3.9 mL/kg, p = 0.720). All animals survived to Day
      14. Trended values over time did not show significant differences-tissue
      oxygenation (p = 0.605), hemoglobin (p = 0.461), PLTs (p = 0.807), WBCs (p =
      0.435), prothrombin time (p = 0.655), activated partial thromboplastin time (p =
      0.416), thromboelastography (TEG)-reaction time (p = 0.265), or TEG-clot
      formation time (p = 0.081). Histopathology did not show significant differences
      between arms. CONCLUSIONS: Mirasol-treated FWB did not impact survival, blood
      loss, tissue oxygen delivery, RBC indices, or coagulation variables in a
      standardized liver injury model. These data suggest that Mirasol-treated FWB is
      both safe and efficacious in vivo.

PMID- 25582336
TI  - Transcriptome analysis of cyclic AMP-dependent protein kinase A-regulated genes
      reveals the production of the novel natural compound fumipyrrole by Aspergillus
      fumigatus.
AB  - Aspergillus fumigatus is an opportunistic human pathogenic fungus causing life
      threatening infections in immunocompromised patients. Adaptation to different
      habitats and also virulence of the fungus depends on signal perception and
      transduction by modules such as the cyclic AMP-dependent protein kinase A (PKA)
      pathway. Here, by transcriptome analysis, 632 differentially regulated genes of
      this important signaling cascade were identified, including 23 putative
      transcriptional regulators. The highest upregulated transcription factor gene was
      located in a previously unknown secondary metabolite gene cluster, which we named
      fmp, encoding an incomplete non-ribosomal peptide synthetase, FmpE.
      Overexpression of the regulatory gene fmpR using the Tet(On) system led to the
      specific expression of the other six genes of the fmp cluster. Metabolic
      profiling of wild type and fmpR overexpressing strain by HPLC-DAD and HPLC-HRESI
      MS and structure elucidation by NMR led to identification of 5-benzyl-1H-pyrrole
      2-carboxylic acid, which we named fumipyrrole. Fumipyrrole was not described as
      natural product yet. Chemical synthesis of fumipyrrole confirmed its structure.
      Interestingly, deletion of fmpR or fmpE led to reduced growth and sporulation of
      the mutant strains. Although fmp cluster genes were transcribed in infected mouse
      lungs, deletion of fmpR resulted in wild-type virulence in a murine infection
      model.

PMID- 25582338
TI  - STAT3 signaling contributes to the high effector activities of interleukin-15
      derived dendritic cells.
AB  - Dendritic cells (DCs) are important innate and adaptive immune effectors, and
      have a key role in antigen presentation and T-cell activation. Different lineages
      of DCs can be developed from hematopoietic progenitors following cytokine
      signaling, and the various lineages of DCs display distinct morphology, phenotype
      and functions. There has been limited information on differential cytokine
      mediated molecular signaling in DCs. Analyses of surface molecules by flow
      cytometry and quantitative RNA profiling revealed differences between DCs derived
      from interleukin-4 (IL-4) versus IL-15 signaling, yet both lineages of DCs
      exhibited similar levels of surface molecules key to immune activation.
      Functional assays confirmed that IL-15-derived DCs elicited greater antigen
      specific, primary and secondary CD8 and CD4 T-cell responses than did IL-4
      derived DCs. Importantly, IL-15 DCs secreted substantial amounts of
      proinflammatory cytokines, including IL-6, interferon-gamma (IFN-gamma) and tumor
      necrosis factor-alpha (TNFalpha), which helped polarize a strong T-cell response.
      Assessment of signaling pathways revealed that IL-15 DCs exhibited a lower levels
      of activated signal transducer and activator of transcription 5 (STAT5), STAT6
      and extracellular signal-regulated kinase 1/2 than IL-4 DCs, but after
      lipopolysaccharide (LPS)/TNFalpha treatment, the STAT3 and p38 mitogen-activated
      protein kinase (MAPK) activities were significantly enhanced in the IL-15 DCs.
      Surprisingly, contrary to the canonical IL-15-mediated STAT5 signaling pathway in
      lymphoid cells, IL-15 did not mediate a strong STAT5 or STAT3 activation in DCs.
      Further analysis using specific inhibitors to STAT3 and p38 MAPK pathways
      revealed that the STAT3 signaling, but not p38 MAPK signaling, contributed to IFN
      gamma production in DCs. Therefore, while IL-15 does not promote the STAT
      signaling in DCs, the increased STAT3 activity after LPS/TNFalpha treatment of
      the IL-15 DCs has a key role in their high IFN-gamma effector activities. 

PMID- 25582337
TI  - Understanding the complexity and malleability of T-cell recognition.
AB  - T cells are the master regulators of immune system function, continually walking
      the biological tightrope between adequate host defence and accidental host
      pathology. Tolerance is maintained or broken through an intricate structural
      interplay between the T-cell receptor (TCR) and major histocompatibility complex
      (MHC) molecule cradling peptide antigens (p). Recent advances in structural
      biology have shown that the TCR/pMHC interface is surprising precise and
      extraordinarily malleable. We have seen that seemingly minor changes in the
      TCR/pMHC interface can abrogate function, as well as substantial conformational
      changes before and after TCR docking. Our understanding of T-cell biology has
      also been altered with the knowledge that MHC molecules can bind not only
      peptides, but also an array of natural and synthetic compounds. Here, we review
      some examples of the precision and flexibility intrinsic to the TCR/p/MHCI axis. 

PMID- 25582339
TI  - Controlling the fire--tissue-specific mechanisms of effector regulatory T-cell
      homing.
AB  - Regulatory T cells have essential roles in regulating immune responses and
      limiting inappropriate inflammation. Evidence now indicates that to achieve this
      function, regulatory T cells must be able to migrate to the most appropriate
      locations within both lymphoid and non-lymphoid organs. This function is achieved
      via the spatiotemporally controlled expression of adhesion molecules and
      chemokine receptors, varying according to the developmental stage of the
      regulatory T cell and the location and environment where they undergo activation.
      In this Review, we summarise information on the roles of adhesion molecules and
      chemokine receptors in mediating regulatory T-cell migration and function
      throughout the body under homeostatic and inflammatory conditions. In addition,
      we review recent studies that have used in vivo imaging to examine the actions of
      regulatory T cells in vivo, in lymph nodes, in the microvasculature and in the
      interstitium of peripheral organs. These studies reveal that the capacity of
      regulatory T cells to undergo selective migration serves a critical role in their
      ability to suppress immune responses. As such, the cellular and molecular
      requirements of regulatory T-cell migration need to be completely understood to
      enable the most effective use of these cells in clinical settings. 

PMID- 25582340
TI  - Multifaceted role of the ubiquitin ligase Itch in immune regulation.
AB  - The HECT-type E3 ligase Itch is increasingly being shown to have a vital role in
      immune regulation. Itch deficiency leads to deleterious inflammatory disorders
      both in mice and humans. By adding ubiquitin to the key signaling intermediates,
      Itch functions as a critical regulator of lymphocyte-cell activation,
      differentiation and immune tolerance. Also, Itch cooperates with deubiquitinating
      enzymes such as A20 and Cyld to terminate NF-kappaB signaling and prevent chronic
      inflammation. This review summarizes recent advances that highlight Itch's role
      in lymphocyte function and explores recent insights regarding its role as a
      regulator of inflammatory signaling. 

PMID- 25582342
TI  - Short hairpin ribonucleic acid constructs targeting insulin-like growth factor
      binding protein-3 rehabilitated decreased testosterone concentrations in diabetic
      rats.
AB  - BACKGROUND: The aim of this study was to determine if shRNA constructs targeting
      insulin-like growth factor binding protein-3 can rehabilitate decreased serum
      testosterone concentrations in streptozotocin-induced diabetic rats.
      MATERIAL/METHODS: After 12 weeks of intracavernous administration of IGFBP-3
      shRNA, intracavernous pressure responses to electrical stimulation of cavernous
      nerves were evaluated. The expression of IGFBP-3 at mRNA and protein levels was
      detected by quantitative real-time PCR analysis and Western blot, respectively.
      The concentrations of serum testosterone and cavernous cyclic guanosine
      monophosphate were detected by enzyme-linked immunosorbent assay. RESULTS: After
      12 weeks of intracavernous administration of IGFBP-3 shRNA, the cavernosal
      pressure was significantly increased in response to the cavernous nerves
      stimulation compared to the diabetic control group (p<0.01). Cavernous IGFBP-3
      expression at both mRNA and protein levels was significantly inhibited. Both
      serum testosterone and cavernous cyclic guanosine monophosphate concentrations
      were significantly increased in the IGFBP-3 shRNA treatment group compared to the
      diabetic control group (p<0.01). CONCLUSIONS: These results suggest that IGFBP-3
      shRNA may rehabilitate erectile function via increases of concentrations of serum
      testosterone and cavernous cyclic guanosine monophosphate in streptozotocin
      induced diabetic rats.

PMID- 25582343
TI  - Staphylococcus aureus sporotrichoid lymphangitis without bacteremia in a
      transplant recipient.
AB  - Pyogenic sporotrichoid infections are rare. There are only 4 reports in the
      literature of Staphylococcus aureus presenting as sporotrichoid lymphangitis
      (also known as lymphocutaneous syndrome or nodular lymphangitis). We report the
      first case, to our knowledge, of S. aureus sporotrichoid infection without
      bacteremia in an immunocompromised organ transplant recipient. 

PMID- 25582344
TI  - Cloxacillin-induced seizure in a hemodialysis patient.
AB  - We are reporting a cloxacillin-induced seizure in a patient with stage 5 chronic
      kidney disease requiring hemodialysis. To our knowledge, there are no published
      case reports of seizures induced by parenteral cloxacillin in hemodialysis
      patients. A young hemodialysis female was admitted to the hospital with decreased
      level of consciousness. Blood cultures revealed methicillin-sensitive
      Staphylococcus aureus where cloxacillin 2 g intravenously every 4 hours was
      initiated. Head computed tomography (CT) was not significant. After 14 hours of
      cloxacillin therapy (4 doses), the patient demonstrated tonic/clonic seizure
      activity, where phenytoin and lorazepam were initiated. The anti-seizure
      medications partially reduced seizure activity. Once the cloxacillin was
      discontinued, the seizures stopped. Two weeks later, all anti-seizure medications
      were stopped with no further seizure activity. Cloxacillin elimination in
      hemodialysis patients is similar to patients with normal kidney function.
      Although cloxacillin does not significantly cross the blood-brain barrier, the
      correlation between the start of seizures and cloxacillin initiation was
      confirmed by the negative CT and blood chemistry laboratory results. Moreover,
      seizure activity was terminated upon discontinuation of cloxacillin. Although
      further investigation for the cause of such seizures is warranted, clinicians
      should use caution when giving high doses of cloxacillin in hemodialysis
      patients. 

PMID- 25582341
TI  - Regulation of CD4 T-cell differentiation and inflammation by repressive histone
      methylation.
AB  - Repressive epigenetic modifications such as dimethylation and trimethylation
      histone H3 at lysine 9 (H3K9me2 and H3K9me3) and H3K27me3 have been shown to be
      critical for embryonic stem (ES) cell differentiation by silencing cell lineage
      promiscuous genes. CD4(+) T helper (T(H)) cell differentiation is a powerful
      model to study the molecular mechanisms associated with cellular lineage choice
      in adult cells. Naive T(H) cells have the capacity to differentiate into one of
      the several phenotypically and functionally distinct and stable lineages.
      Although some repressive epigenetic mechanisms have a critical role in T(H) cell
      differentiation in a similar manner to that in ES cells, it is clear that there
      are disparate functions for certain modifications between ES cells and T(H)
      cells. Here we review the role of repressive histone modifications in the
      differentiation and function of T(H) cells in health and disease.

PMID- 25582346
TI  - The prognostic value of phosphorylated Akt in breast cancer: a systematic review.
AB  - The prognostic value of phosphorylated Akt (pAkt) overexpression in breast cancer
      has been investigated by many studies with inconsistent results. This systematic
      review was conducted to evaluate the association of pAkt overexpression with
      breast cancer prognosis in terms of overall survival and disease-free survival.
      Three electronic databases (PubMed, EMBASE and Chinese Biomedical Literature
      Database) were comprehensively searched. Hazard ratios (HRs) with 95% confidence
      intervals (CIs) from different studies were combined using the random-effects
      model. In total, 33 studies with 9,836 patients were included for final analysis.
      The summary HR for overall survival and disease-free survival was 1.52 (95% CI:
      1.29-1.78) and 1.28 (95% CI: 1.13-1.45), respectively, indicating higher risk of
      death and disease recurrence associated with pAkt overexpression. The results
      were robust in sensitivity analyses by omitting one study each time and by using
      the fixed-effects model instead. Subgroup and meta-regression analyses did not
      show that the prognostic effect of pAkt overexpression would change materially
      with such factors as population, status of hormone receptors, hormonal or
      trastuzumab treatment given, analyzing method (univariate versus multivariate)
      and methodological quality of the original studies. In conclusion, the available
      evidence suggests that pAkt overexpression is an adverse prognostic factor for
      breast cancer. 

PMID- 25582348
TI  - Antioxidant effects of proanthocyanidin-rich natural extracts from grape seed and
      cupuassu on gastrointestinal mucosa.
AB  - BACKGROUND: The gastrointestinal tract (GI) is constantly exposed to reactive
      species released by the GI tract itself, and those present in food and beverages.
      Phenolic compounds may help in protecting the GI tract against damage produced by
      the reactive species. In this paper we have analyzed the effects of a grape seed
      proanthocyanidin extract (GSPE) on reactive oxygen species (ROS) production in
      two different intestinal cell types: the absorptive cell line Caco-2 and the
      enteroendocrine cell line STC-1. RESULTS: We show that GSPE prevents tert
      butylhydroperoxide-induced oxidative stress in both cell lines, and that the
      effects are dose and time dependent. We have also analyzed whether GSPE has any
      in vivo effect, and found that 25 mg kg(-1) body weight cannot counteract the
      increase in intestinal ROS induced by the cafeteria diet. However, an acute (1 h)
      treatment of 1 g GSPE kg(-1) body weight reduced ROS in fasted animals and also
      decreased ROS induction by food. These effects were found only after a short-term
      treatment. Furthermore, we have compared the in vitro GSPE effects with those of
      another proanthocyanidin-rich extract from cupuassu seeds, though it has
      compounds with different structures. Cupuassu extract also shows antioxidant
      effects in both cell types, which suggests different mechanisms from those of
      GSPE. CONCLUSION: Natural proanthocyanidin-rich extracts have an antioxidant
      effect in the GI tract, acting on absorptive cells and enterohormone-secreting
      cells, although the effects depend on the dose and period of treatment. (c) 2015
      Society of Chemical Industry.

PMID- 25582347
TI  - Genomic and metabolic analysis of fluoranthene degradation pathway in
      Celeribacter indicus P73T.
AB  - Celeribacter indicus P73(T), isolated from deep-sea sediment from the Indian
      Ocean, is capable of degrading a wide range of polycyclic aromatic hydrocarbons
      (PAHs) and is the first fluoranthene-degrading bacterium within the family
      Rhodobacteraceae. Here, the complete genome sequence of strain P73(T) is
      presented and analyzed. Besides a 4.5-Mb circular chromosome, strain P73(T)
      carries five plasmids, and encodes 4827 predicted protein-coding sequences. One
      hundred and thirty-eight genes, including 14 dioxygenase genes, were predicted to
      be involved in the degradation of aromatic compounds, and most of these genes are
      clustered in four regions. P73_0346 is the first fluoranthene 7,8-dioxygenase to
      be discovered and the first fluoranthene dioxygenase within the toluene/biphenyl
      family. The degradative genes in regions B and D in P73(T) are absent in
      Celeribacter baekdonensis B30, which cannot degrade PAHs. Four intermediate
      metabolites [acenaphthylene-1(2H)-one, acenaphthenequinone, 1,2
      dihydroxyacenaphthylene, and 1,8-naphthalic anhydride] of fluoranthene
      degradation by strain P73(T) were detected as the main intermediates, indicating
      that the degradation of fluoranthene in P73(T) was initiated by dioxygenation at
      the C-7,8 positions. Based on the genomic and metabolitic results, we propose a C
      7,8 dioxygenation pathway in which fluoranthene is mineralized to TCA cycle
      intermediates. 

PMID- 25582349
TI  - The influence of component alignment on patellar kinematics in total knee
      arthroplasty.
AB  - BACKGROUND AND PURPOSE: Postoperative anterior knee pain is one of the most
      frequent complications after total knee arthroplasty (TKA). Changes in patellar
      kinematics after TKA relative to the preoperative arthritic knee are not well
      understood. We compared the patellar kinematics preoperatively with the
      kinematics after ligament-balanced navigated TKA. PATIENTS AND METHODS: We
      measured patellar tracking before and after ligament-balanced TKA in 40
      consecutive patients using computer navigation. Furthermore, the influences of
      different femoral and tibial component alignment on patellar kinematics were
      analyzed using generalized linear models. RESULTS: After TKA, the patellae
      shifted statistically significantly more laterally between 30 degrees  and 60
      degrees . The lateral tilt increased at 90 degrees  of flexion whereas the
      epicondylar distance decreased between 45 degrees  and 75 degrees  of flexion.
      Sagittal component alignment, but not rotational component alignment, had a
      significant influence on patellar kinematics. INTERPRETATION: There are major
      differences in patellar kinematics between the preoperative arthritic knee and
      the knee after TKA. Combined sagittal component alignment in particular appears
      to have a major effect on patellar kinematics. Surgeons should be especially
      aware of altering preoperative sagittal alignment until the possible clinical
      relevance has been investigated.

PMID- 25582350
TI  - The regulators of yeast PHO system participate in the transcriptional regulation
      of G1 cyclin under alkaline stress conditions.
AB  - The yeast Pho85 kinase oversees whether environmental conditions are favourable
      for cell growth and enables yeast cells to express only genes that are
      appropriate for the conditions. Alkaline stress perturbs transport of molecules
      across the plasma membrane that is vital for cell survival. Progression through
      the cell cycle is halted until the cells can adapt to the stress conditions. I
      found that Pho85 is required for CLN2 expression and that overproduction of the
      transcription factors Pho4, Rim101 and Crz1, all targets of Pho85, inhibited CLN2
      expression. CLN2 expression in the absence of Pho85 could be recovered only when
      all the three transcription factors were deleted. Whi5, a functional homologue of
      the mammalian Rb protein, represses CLN2 expression and is inactivated when
      phosphorylated by either of the CDK-cyclin complexes, Cdc28-Cln3 or Pho85-Pcl9.
      Under alkaline conditions, the absence of Whi5 caused an increase in CLN2
      expression but failed to do so when Pho85 was also absent, or when Pho4 was
      overproduced. The expression level of CLN2 in a Deltapho85 Deltapho4 Deltarim101
      Deltacrz1 quadruple mutant was stimulated when the Whi5 activity was repressed by
      overproduction of Pho85-Pcl9. These results indicate that Whi5 is also under
      control of alkaline stress. The inhibitory function of Whi5 on CLN2 is dependent
      on Rpd3 HDAC, and the absence of Rpd3 could also suppress the inhibitory effect
      of Pho4 overproduction. Based on these findings, a model is presented in which
      Pho85 and Pho4 functions in CLN2 regulation under alkaline conditions.

PMID- 25582352
TI  - Single-cell analysis reveals heterogeneity in onset of transgene expression from
      synthetic tetracycline-dependent promoters.
AB  - Synthetic promoters have been designed for mammalian cells to achieve both
      temporal and quantitative control over transgene expression without interfering
      with the endogenous cellular network. Routine applications of synthetic
      expression systems are based on steady-state measurements of gene expression
      while the mechanism by which these steady-states are realised at the single-cell
      level has not been investigated. We focused on the elucidation of the kinetics of
      doxycycline-controlled synthetic modules as a paradigm. Following gene expression
      in single cells, we observed a gradual increase of transgene expression within
      the first 48 h after activation, as determined by flow cytometry. Time-lapse
      microscopy revealed that the onset of transgene expression was highly variable in
      individual cells. Interestingly, a bidirectional cassette design showed
      significantly reduced cell-to-cell heterogeneity in expression. Of note, the
      influence of the cell cycle seems to be negligible, since the onset of expression
      correlates with cell division in only a minor fraction of the cell population. In
      contrast, rapid and synchronous transgene expression could be realized using a
      posttranslational regulation system that relies on ligand-induced stabilization
      of a tagged protein. Thus, the inherent temporal variability of transcriptionally
      regulated synthetic transgene expression systems has to be considered for kinetic
      and correlative experimental applications. 

PMID- 25582353
TI  - A sodium ion intercalation material: a comparative study of amorphous and
      crystalline FePO4.
AB  - Due to their low cost, high abundance and eco-friendly features, Na-ion batteries
      are becoming alternative choices for rechargeable batteries, especially in large
      scale applications. Generally, the well-crystallized materials have many
      advantages over amorphous materials, such as long cycle life, high rate
      performance and other electrochemical properties. However, the amorphous FePO4 we
      report here exhibits outstanding cycling stability and rate performance which are
      derived from its amorphous nature and wafer-like porous morphology. A comparative
      study of amorphous and crystalline FePO4 has been carried out as cathode
      materials for Na-ion batteries. The present study not only reports a synthetic
      method which is facile, inexpensive, and scalable for mass production, but it
      also motivates further exploration of other amorphous materials for Na-ion
      batteries. 

PMID- 25582351
TI  - Clinical management of hereditary colorectal cancer syndromes.
AB  - Hereditary factors are involved in the development of a substantial proportion of
      all cases of colorectal cancer. Inherited forms of colorectal cancer are usually
      subdivided into polyposis syndromes characterized by the development of multiple
      colorectal polyps and nonpolyposis syndromes characterized by the development of
      few or no polyps. Timely identification of hereditary colorectal cancer syndromes
      is vital because patient participation in early detection programmes prevents
      premature death due to cancer. Polyposis syndromes are fairly easy to recognize,
      but some patients might have characteristics that overlap with other clinically
      defined syndromes. Comprehensive analysis of the genes known to be associated
      with polyposis syndromes helps to establish the final diagnosis in these
      patients. Recognizing Lynch syndrome is more difficult than other polyposis
      syndromes owing to the absence of pathognomonic features. Most investigators
      therefore recommend performing systematic molecular analysis of all newly
      diagnosed colorectal cancer using immunohistochemical methods. The implementation
      in clinical practice of new high-throughput methods for molecular analysis might
      further increase the identification of individuals at risk of hereditary
      colorectal cancer. This Review describes the clinical management of the various
      hereditary colorectal cancer syndromes and demonstrates the advantage of using a
      classification based on the underlying gene defects. 

PMID- 25582354
TI  - Recovery characteristics of the electrically stimulated auditory nerve in
      deafened guinea pigs: relation to neuronal status.
AB  - Successful cochlear implant performance requires adequate responsiveness of the
      auditory nerve to prolonged pulsatile electrical stimulation. Degeneration of the
      auditory nerve as a result of severe hair cell loss could considerably compromise
      this ability. The main objective of this study was to characterize the recovery
      of the electrically stimulated auditory nerve, as well as to evaluate possible
      changes caused by deafness-induced degeneration. To this end we studied temporal
      responsiveness of the auditory nerve in a guinea pig model of sensorineural
      hearing loss. Using masker-probe and pulse train paradigms we compared
      electrically evoked compound action potentials (eCAPs) in normal-hearing animals
      with those in animals with moderate (two weeks after ototoxic treatment) and
      severe (six weeks after ototoxic treatment) loss of spiral ganglion cells (SGCs).
      Masker-probe interval and pulse train inter-pulse interval was varied from 0.3 to
      16 ms. Whereas recovery assessed with masker-probe was roughly similar for normal
      hearing and both groups of deafened animals, it was considerably faster for six
      weeks deaf animals (tau ~ 1.2 ms) than for two weeks deaf or normal-hearing
      animals (tau ~ 3-4 ms) when 100-ms pulse trains were applied. Latency increased
      with decreasing inter-pulse intervals, and this was more pronounced with pulse
      trains than with masker-probe stimulation. With high frequency pulse train
      stimulation eCAP amplitudes were modulated for deafened animals, meaning that
      amplitudes for odd pulse numbers were larger than for even pulses. The relative
      refractory period (tau) and the modulation depth of the eCAP amplitude for pulse
      trains, as well as the latency increase for both paradigms significantly
      correlated with quantified measures of auditory nerve degeneration (size and
      packing density of SGCs). In addition to these findings, separate masker-probe
      recovery functions for the eCAP N1 and N2 peaks displayed a robust non-monotonic
      or shoulder-shaped course in all animals. The time interval between the N1 and N2
      correlated with neuronal refractoriness, suggesting that the N2 peak reflects a
      second firing of part of the SGC population. We conclude that - compared to the
      commonly used masker-probe recovery functions - recovery functions obtained with
      pulse train stimulation may provide a means to augment differences and, by doing
      so, to more potently discriminate between auditory nerve conditions.

PMID- 25582355
TI  - Cortical and trabecular load sharing in the human femoral neck.
AB  - The relative role of the cortical vs trabecular bone in the load-carrying
      capacity of the proximal femur-a fundamental issue in both basic-science and
      clinical biomechanics-remains unclear. To gain insight into this issue, we
      performed micro-CT-based, linear elastic finite element analysis (61.5-micron
      sized elements; ~280 million elements per model) on 18 proximal femurs (5M, 13F,
      ages 61-93 years) to quantify the fraction of frontal-plane bending moment shared
      by the cortical vs trabecular bone in the femoral neck, as well as the associated
      spatial distributions of stress. Analyses were performed separately for a
      sideways fall and stance loading. For both loading modes and across all 18 bones,
      we found consistent patterns of load-sharing in the neck: most proximally, the
      trabecular bone took most of the load; moving distally, the cortical bone took
      increasingly more of the load; and more distally, there was a region of uniform
      load-sharing, the cortical bone taking the majority of the load. This distal
      region of uniform load-sharing extended more for fall than stance loading (77 +/-
      8% vs 51 +/- 6% of the neck length for fall vs. stance; mean +/- SD) but the
      fraction of total load taken by the cortical bone in that region was greater for
      stance loading (88 +/- 5% vs. 64 +/- 9% for stance vs. fall). Locally, maximum
      stress levels occurred in the cortical bone distally, but in the trabecular bone
      proximally. Although the distal cortex showed qualitative stress distributions
      consistent with the behavior of an Euler-type beam, quantitatively beam theory
      did not apply. We conclude that consistent and well-delineated regions of uniform
      load-sharing and load-transfer between the cortical and trabecular bone exist
      within the femoral neck, the details of which depend on the external loading
      conditions.

PMID- 25582356
TI  - Bone cell mechanosensitivity, estrogen deficiency, and osteoporosis.
AB  - Adaptation of bone to mechanical stresses normally produces a bone architecture
      that combines a proper resistance against failure with a minimal use of material.
      This adaptive process is governed by mechanosensitive osteocytes that transduce
      the mechanical signals into chemical responses, i.e. the osteocytes release
      signaling molecules, which orchestrate the recruitment and activity of bone
      forming osteoblasts and/or bone resorbing osteoclasts. Computer models have shown
      that the maintenance of a mechanically-efficient bone architecture depends on the
      intensity and spatial distribution of the mechanical stimulus as well as on the
      osteocyte response. Osteoporosis is a condition characterized by a reduced bone
      mass and a compromized resistance of bone against mechanical loads, which has led
      us to hypothesize that mechanotransduction by osteocytes is altered in
      osteoporosis. One of the major causal factors for osteoporosis is the loss of
      estrogen, the major hormonal regulator of bone metabolism. Loss of estrogen may
      increase osteocyte-mediated activation of bone remodeling, resulting in impaired
      bone mass and architecture. In this review we highlight current insights on how
      osteocytes perceive mechanical stimuli placed on whole bones. Particular emphasis
      is placed on the role of estrogen in signaling pathway activation by mechanical
      stimuli, and on computer simulation in combination with cell biology to unravel
      biological processes contributing to bone strength. 

PMID- 25582358
TI  - A GPU-implemented physics-based haptic simulator of tooth drilling.
AB  - BACKGROUND: Restorative dentistry simulation is one of the most challenging
      applications involving virtual reality and haptics. This paper presents a haptics
      based tooth drilling simulator for dental education. METHODS: Unlike the existing
      methods, the force model is based on physical properties which consider the
      geometrical model of the tool. In order to provide uniform force feedback from
      tooth layers, a new approach is suggested in which the physical properties of
      each tooth voxel are subsequently used in calculating the feedback force. We
      implement a hashing algorithm for collision detection due to its reduced time
      complexity. The haptics algorithm has been implemented on a graphics processing
      unit using the CUDA toolbox. RESULTS: In parallel processing, the speed of haptic
      loop execution is increased almost 8 times. CONCLUSION: The proposed idea for
      force calculation leads to a uniform sensation of force. An important feature of
      the designed system is the capability to run in a real-time fashion.

PMID- 25582359
TI  - [Discussion on the necessity and feasibility of the normalization of HIV/AIDS
      prevention and control].

PMID- 25582357
TI  - Mitochondria DNA mutations cause sex-dependent development of hypertension and
      alterations in cardiovascular function.
AB  - Aging is associated with conduit artery stiffening that is a risk factor for and
      can precede hypertension and ventricular dysfunction. Increases in mitochondria
      DNA (mtDNA) frequency have been correlated with aging. Mice with a mutation in
      the encoding domain (D257A) of a proof-reading deficient version of mtDNA
      polymerase-gamma (POLG) have musculoskeletal features of premature aging and a
      shortened lifespan. However, few studies using these mice have investigated the
      effects of mtDNA mutations on cardiovascular function. We hypothesized that the
      proof-reading deficient mtDNA POLG leads to arterial stiffening, hypertension,
      and ventricular hypertrophy. Ten to twelve month-old D257A mice (n=13) and age-
      and sex-matched wild-type controls (n=13) were catheterized for hemodynamic and
      ventricular function measurements. Left common carotid arteries (LCCA) were
      harvested for mechanical tests followed by histology. Male D257A mice had
      pulmonary and systemic hypertension, arterial stiffening, larger LCCA diameter
      (701+/-45 vs. 597+/-60MUm), shorter LCCA axial length (8.96+/-0.56 vs. 10.10+/
      0.80mm), and reduced hematocrit (29.1+/-6.1 vs. 41.3+/-8.1; all p<0.05). Male and
      female D257A mice had biventricular hypertrophy (p<0.05). Female D257A mice did
      not have significant increases in pressure or arterial stiffening, suggesting
      that the mechanisms of hypertension or arterial stiffening from mtDNA mutations
      differ based on sex. Our results lend insight into the mechanisms of age-related
      cardiovascular disease and may point to novel treatment strategies to address
      cardiovascular mortality in the elderly. 

PMID- 25582360
TI  - [Mobility of HIV/AIPS and affecting factors anlysis in 2013, China].
AB  - OBJECTIVE: To analyze the factors of people living with HIV/AIDS and mobility in
      2013 who were reported before 2012 in China. METHODS: Data were collected through
      China HIV/AIDS case reporting information system in 2012 and 2013. A total of 300
      349 HIV/AIDS cases reported before 2012 have been included in this study and have
      been visited in 2013.SPSS software was used to conduct multivariate logistic
      regression model. RESULTS: A total of 300 349 HIV/AIDS cases have been included
      in the study and 5.4% (16 088/300 349) objects have changed their residential
      locations in 2013. The movements mostly happened inside local province, which
      accounted for 69.1% (11 114/16 088).In Yunnan,Guangdong, and Guangxi province,
      the mobile percentage were 85.8% (2 377/2 771), 58.5% (1 534/2 621) and 78.1% (1
      470/1 883) that movements happened inside local province. Multivariate logistic
      regression analysis showed that male (12 478 cases,OR = 1.97, 95%CI: 1.03-1.12),
      HIV infection (12 125 cases,OR = 1.99, 95%CI: 1.92-2.0), 15-49 age group (15 144
      cases,OR = 2.16, 95%CI: 2.00-2.32) were more mobile. CONCLUSION: The movements
      mostly happened inside local province in 2013 in China and population movements
      tends to happen in young men infected with HIV.

PMID- 25582361
TI  - [Social network analysis and high risk behavior characteristics of recreational
      drug users: a qualitative study].
AB  - OBJECTIVE: To understand the characteristics of recreational drug users'
      behaviors and social network, as well as their potential impact to the
      transmission of sexual transmitted infections (STI). METHODS: Qualitative
      interview was used to collect information on rough estimation of population size
      and behavior change before and after recreational drug use. A total of 120
      participants were recruited by convenient sampling from April to October, 2013 in
      a community of Qingdao city. Blood specimens were taken for HIV/syphilis
      serological testing and social network analysis was performed to understand the
      characteristics of their behavior and social network. RESULTS: All participants
      used methamphetamine and 103 of them showed social connection. The prevalence of
      syphilis and HIV were 24.2% (29/120) and 2.5% (3/120) respectively. The estimated
      size of recreational drug users was big with a wide diversity of occupations and
      age range, and males were more frequent than females. Drug use may affect condom
      use and frequent drug users showed symptom of psychosis and neuro-toxicities. The
      size of social network was 2.45 +/- 1.63 in the past 6 months, which indicated an
      increasing trend of the sexual partner number and risky behaviors. CONCLUSION:
      Recreational drug use could increase the size of social network among sex
      partners, the frequency of risky sexual behaviors and syphilis prevalence, which
      indicate a high risk of HIV/STI among this population as well as a huge burden of
      disease prevention and control in the future.

PMID- 25582362
TI  - [A study on the effectiveness of prevention of mother-to-child HIV, syphilis, and
      hepatitis B transmission among pregnant women in Dehong prefecture,Yunnan
      province, China from 2011 to 2013].
AB  - OBJECTIVE: To demonstrate the effectiveness of prevention of mother-to-child HIV,
      syphilis, and hepatitis B transmission among pregnant women in Dehong prefecture,
      Yunnan province, China from 2011 to 2013. METHODS: Data were collected mainly
      from the continuous HIV surveillance system and prevention of mother-to-child
      transmission (PMTCT) reporting system of Dehong prefecture, and supplemented by
      annual reported data on HIV, syphilis, and hepatitis B PMTCT to know the general
      demographic characteristics, HIV testing and counseling service, PMTCT service,
      and other medical services. Data were presented as absolute numbers and
      proportions. RESULTS: From 2011 to 2013, the number of pregnant women
      participating in HIV, syphilis, and hepatitis B testing in Dehong prefecture
      increased and the HIV testing rates were 99.2% (18 694/18 854), 99.9% (22 047/22
      060) and 99.9% (21 751/21 756), the syphilis testing rates were 56.0% (10 550/18
      854), 99.6% (21 980/22 060) and 99.9% (21 751/21 756), and the hepatitis B
      testing rates were 60.2% (11 358/18 854), 99.6% (21 974/22 060) and 99.9% (21
      751/21 756). From 2011 to 2013, the HIV positive rates were 0.87% (327/37
      787),0.82% (319/38 817) and 0.85% (315/37 261), the syphilis positive rates were
      0.05% (10/18 520),0.12% (43/36 817) and 0.11% (40/35 888), the hepatitis B
      positive rates were 2.46% (456/18 520), 2.23% (794/35 547) and 2.14% (739/34
      468), respectively. The rates of HIV-positive pregnant women giving birth in
      hospitals were 99.2% (128/129), 100.0% (141/141) and 100.0% (141/141). From 2011
      to 2013, the proportions of HIV-positive pregnant women receiving antiretroviral
      therapy were 99.2% (128/129), 99.3% (140/141) and 99.3% (140/141), respectively.
      And the treatment rate of syphilis-positive pregnant women were 71% (5/7), 89%
      (16/18) and 97% (32/33). The rates of hepatitis B immunoglobulin injection among
      new-borns of hepatitis B-positive pregnant women were 92.9% (263/283), 99.7%
      (612/614) and 99.4% (629/633). The estimated rates of mother-to-child
      transmission of HIV were 2.28%, 2.30% and 3.00%, respectively. CONCLUSION: There
      was an increasing trend of HIV, syphilis, and hepatitis B testing rate and the
      positive rate kept at a low level. The proportions of HIV-positive pregnant women
      receiving HIV, syphilis, and hepatitis B PMTCT services increased annually, while
      the proportion of HIV MTCT kept at an overall low level from 2011 to 2013, which
      indicated its effectiveness of HIV PMTCT work during recent years in Dehong
      prefecture,Yunnan province, China.

PMID- 25582363
TI  - [Analysis of the five-year effectiveness of highly active antiretroviral therapy
      among 200 HIV/AIDS patients in Jiangsu province].
AB  - OBJECTIVE: To analyze the five-year effectiveness of the people living with
      HIV/AIDS who initially received highly active antiretroviral therapy (HAART) in
      Jiangsu province. METHODS: HIV/AIDS initially received HAART from 1 Jan 2005 to
      31 May 2014 in Jiangsu province with the CD4(+)T cell count tested in baseline, 6
      months, 1 year, 2 years, 3 years, 4 years and 5 years after treatment initiation
      were selected. According to their retrospectively collected baseline and follow
      up data, statistical analysis was performed using SPSS 16.0 software to analyze
      the variation of CD4(+)T counts and its impact factors in different times after
      treatment initiation. RESULTS: A total of 200 patients were included. A total of
      134 patients were men, and 66 were women, the ratio of male to female was 2.03:
      1; mean age was (39.7 +/- 10.3) years old; 69.0% (138/200) of the patients
      married; 53.0% (106/200) as the most were infected with HIV through heterosexual
      transmission, and followed by men who have sex with men (MSM) (25.5%, 51/200);
      taken together as 78.5% (157/200).58.5% (117/200) were treated in the CDC. The
      mean (95%CI) baseline CD4(+)T cell count of cases was 106.9 (93.3-120.5)
      cells/ul; the CD4(+)T count tested in 6 months, 1 year, 2 years, 3 years, 4 years
      and 5 years after treatment initiation were 107.3, 152.9, 221.6, 260.0, 281.3 and
      316.4 cells/ul more than baseline respectively; the CD4(+)T count after treatment
      initiation has increased over time (F = 201.06, P < 0.01) . The mean(95%CI)
      CD4(+)T count tested in 5 years after treatment initiation can increase to
      540.7(445.4-635.9) cells/ul with a baseline CD4(+)T count more than 200 cells/ul,
      but in the subgroups with a baseline CD4(+)T count less than or equal to 50
      cells/ul, 51-100 cells/ul, 101-150 cells/ul and 151-200 cells/ul, it only can
      reach to 431.4 (375.9-487.0), 400.0 (339.9-460.2), 380.3 (330.6-430.0) and 412.1
      (369.3-454.8) cells/ul respectively. The mean (95%CI) CD4(+)T count tested in 5
      years after treatment initiation with 1 baseline symptom categories can increase
      to 449.2 (392.2-506.2) cells/ul, while 409.1(317.8-500.5)cells/ul in the subgroup
      with baseline symptom categories more than or equal to 2. The CD4(+)T after
      treatment increased slowly associated with a lower baseline CD4(+)T count level
      and more baseline symptom categories (F values were 3.96 and 2.35, P < 0.01).
      CONCLUSION: It has a remarkable effectiveness for HIV/AIDS treatment in Jiangsu
      province. The patients with a baseline CD4(+)T count more than 200 counts/ul have
      a better immune function recovery.

PMID- 25582364
TI  - [Study on the mortality and risk factors among HIV/AIDS patients receiving
      antiretroviral therapy in Xinjiang Uygur Autonomous Region].
AB  - OBJECTIVE: To analyze the mortality and risk factors among HIV/AIDS patients
      receiving highly active antiretroviral therapy (HAART) in the Xinjiang Uyghur
      Autonomous Region (XUAR). METHODS: The objects of study were all HIV/AIDS adult
      patients who had received HAART in XUAR. The proceeding information was uploaded
      to the national ART reporting system which was a branch of the national HIV/AIDS
      reporting system. A retrospective cohort study was conducted among these patients
      who were treated during July 2004 to June 2013 in XUAR. Mortality rates and
      cumulative survival rates were calculated. Cox proportional hazard model was
      conducted to examine the risk factors for deaths. RESULTS: The proportion for
      death, lost, referral and withdrawal were 8.5% (1 200/14 062), 2.5% (351/14 062),
      0.9% (121/14 062)and 15.4% (2 162/14 062) respectively. The P25, P50 and P75 of
      baseline CD4(+)T lymphocyte was 144.00, 244.50 and 331.00/ul, respectively. The
      overall mortality rate was 4.98/100 person-years. The cumulative survival rate of
      ART treatment after 1-5 years were 0.94,0.91,0.88, 0.84 and 0.81. The mortality
      rate had a significant difference among different population. The male (6.58/100
      person-years) was higher than the female(2.87/100 person-years), the people who
      infected tuberculosis (TB) (9.79/100 person-years) was higher than those non TB
      (4.12/100 person-years), the people whose CD4(+)T lymphocyte count less than
      200/ul (7.67/100 person-years) was higher than other groups, the people who were
      transmitted through injection (7.61/100 person-years) was higher than those
      sexual transmission (3.10/100 person-years), the people whose HB less than 80 g/L
      (13.84/100 person-years) was higher than those more than 80 g/L (4.74/100 person
      years) (chi(2) values were 154.62, 177.47, 309.73, 228.99 and 84.27. P < 0.01).
      The risk of death of the one with the baseline CD4(+)T lymphocyte <= 200/ul was
      3.61 (2.73-4.78) times of the one with the baseline CD4(+)T lymphocyte >350/ul.
      The risk of death of the one having more than 4 baseline symptom categories was
      3.62 (2.42-5.42) times of the one having less than 3 baseline symptom categories.
      The risk of death of the one with baseline HB >= 80 g/L was 2.84 (2.21-3.64)
      times of the one with the baseline HB <80 g/L. The risk of death of the male was
      1.48 (1.25-1.75) times of the female. The risk of death of the one infected TB
      was 1.39(1.18-1.64) times of the one not infected TB. The risk of death of the
      one injecting drugs was 1.84 (1.56-2.17) times of the one not injecting drugs.
      CONCLUSION: From 2004 to 2013, the mortality rate was low among HIV/AIDS patients
      receiving ART in XUAR. The mortality risk factors were low CD4 T cell count,
      having more baseline symptom categories, low HB level, injection drug
      transmission, male and TB infection, all these factors had positive correlation
      with death.

PMID- 25582365
TI  - [Analysis of antiviral therapy HIV/AIDS children from Shandong province].
AB  - OBJECTIVE: To analyze the outcome among HIV-infected children following
      antiretroviral treatment in Shandong province. METHODS: From the national AIDS
      antiviral treatment database during April 2009 and December 2013, 50 children who
      were according to antiviral treatment in Shandong province were classified as the
      cases. Regular follow-up observation and test were conducted among children under
      antiretroviral therapy before treatment,0.5(th), 1(th), 2(th), 3(th), 6(th),
      9(th), 12(th) months after treatment, and then one time after every 3 months
      follow-up after one year. The height and weight of the children under
      antiretroviral therapy and normal children (2010 national student physical health
      survey results)were compared during different times. And the height and weight of
      the follow-up period of situation, the CD4(+)T cell count and viral load, regular
      physical examination results, the incidence of opportunistic infections were
      compared with baseline data. RESULTS: Among the 50 children under antiviral
      therapy, male accounted for 54.0% (27/50) , female 46.0% (23/50) , the youngest
      was 2 years of age, the oldest was 15 years old, and all of them were transmitted
      by the mother-to-child route and none received mother-to-child prevention. The
      shortest treatment time lasted five months, the longest 61 months, with a median
      25 months. The height of the baseline, 12(th), 24(th), 36(th) months after
      antiviral treatment were ( 111.9 +/- 23.4), (118.1 +/- 20.9), (127.1 +/- 13.9),
      (135.4 +/- 10.2)cm, and weigh were ( 20.6 +/- 8.7), (23.8 +/- 6.3), (27.8 +/-
      7.2), (30.7 +/- 5.5) kg, respectively. The height and weight of the treated
      children were higher than those in the baseline (P < 0.05), but lower than those
      among the children without HIV infection. The CD4(+)T lymphocytes level of the
      baseline, 3(th), 6(th), 12(th), 24(th), 36(th) months after antiviral treatment
      were 224.0, 279.5, 465.0, 581.0, 640.0, 728.0/ul, the CD4(+)T lymphocytes level
      after antiviral treatment were higher than the baseline (P < 0.05). Hemoglobin
      and AST were significantly different between children received treatment after 24
      months and those in the baseline (P < 0.05), baseline and 24(th) months after
      treatment the hemoglobin value were (106.6 +/- 22.2), (125.2 +/- 5.8), and the
      AST measurements were (42.1 +/- 23.1), (23.4 +/- 15.6). Baseline and 12(th),
      24(th) months after treatment, the median of viral load were 10 000.0, 105.0,0.0
      copies/ml , and the ratio of viral load <= 400 copies/ml were 50% (4/8) , 65%
      (22/34) , 88% (14/16) , respectively, the results of viral load had significant
      difference among 12(th), 24(th) months after antiviral treatment and baseline (P
      < 0.05). The incidence of opportunistic infections was 62% (31/50) before
      treatment, and 12% (6/50) after the antiviral therapy. CONCLUSION: Antiviral
      therapy can effectively improve the immunity and reduce the incidence of
      opportunistic infections which is helpful to improve the quality of life among
      HIV-infected children following antiretroviral treatment in Shandong province.

PMID- 25582366
TI  - [Analysis of characteristics and therapy of clients in the extension methadone
      maintenance therapy clinic].
AB  - OBJECTIVE: To understand the characteristics and retention situation of clients
      in extension clinic of methadone maintenance therapy. METHODS: From December 20,
      2010 to March 10, 2011, the system sampling method was used to get the cases. A
      total of 462 heroin addicts from 22 methadone maintenance therapy clinics and
      extension clinics located in Mangshi, Ruili, Longchuan, Yingjiang, Lianghe of
      Dehong prefecture, Yunnan province were interviewed, and the demographic
      characteristics, quality of life, urine testing results for morphine of the
      patients between the extension MMT clinic and standard MMT clinic were also
      collected and compared. A cohort study was conducted to analyze retention
      situation of the new clients with Kaplan Meier method during 9 months treatment.
      RESULTS: Of the 462 cases, 239 cases were from standard MMT clinic, and 223 cases
      were from the extension MMT clinic. Among them, 117 cases were new research
      objects into the group during the investigation. Among the clients of extension
      MMT clinic, 96.7% (147/152) of them were males, 37.5% (57/152) were Dai
      nationality, and 61.2% (93/152) were married, 38.8% (59/152) with primary school
      education, 95.4% (145/152) lived with their family or relatives, 96.7% (147/152)
      could arrive at the clinic from their habitation within 15 minutes. The positive
      detection rates 72% (13/18), 71% (24/34), 58% (30/52), 29% (15/52), 14% (6/44),
      14% (4/29), 15% (5/34), 17% (6/35), 6% (2/33), 16% (5/31) of urine-morphine
      testing among new clients of extension MMT clinics decreased as the period of
      treatment lengthened (chi(2) = 61.04, P < 0.05). The period of retention of the
      clients in extension MMT clinics was 175-days averagely, with an average
      retention 122 days of when withdrawing. The retention rates of the clients were
      52% (37/71)and 61% (28/46) at 9th month of the extension MMT clinics and standard
      MMT clinics respectively. There was no difference in the retention rate between
      those of two types of clinics (chi(2) = 0.82, P = 0.37) . CONCLUSION: Most of the
      clients in extension MMT clinics lived with their family or relatives, and spent
      less time on the way to the clinics. After 9 months methadone maintenance
      therapy, the quality of life of clients in extension clinics was improved while
      addiction among them decreased. The extension clinic was an effective strategy
      for retention in remote areas.

PMID- 25582367
TI  - [The status of HIV disclosure to primary sexual partners and sexual behaviors
      among HIV-infected men who have sex with men of 3 cities in China].
AB  - OBJECTIVE: To investigate the status of HIV disclosure to primary partners and to
      explore the correlates of HIV disclosure among HIV-infected men who have sex with
      men (MSM) in Guangzhou, Chongqing and Chengdu. METHODS: This survey was conducted
      in Chengdu, Chongqing and Guangzhou by using "snowballing" sample from December,
      2012 to May, 2013. Participants who were eighteen years old or elder, HIV
      infected, had sex with men and lived in three cities when the survey was
      conducted were eligible for subjects of this survey. Primary partners and
      disclosure status of participants were investigated. Multiple Unconditioned
      Logistic Regression analysis was used to analyze the influence factors associated
      with HIV disclosure.Of 600 participants, 541 were excluded because of logical
      problem or incomplete items in questionnaire and the effective response rate was
      90.2%. RESULTS: Of the 541 HIV-positive MSM participants, the mean age was (30.2
      +/- 7.7) years old, 78.2% (423/541) of the participants had male primary
      partners.Of the 423 participants who had male primary partner, 10.9% (46/423) had
      wife, 58.9% (249/423) had one primary partner, and 41.1% (174/423) had two or
      more. The proportion of HIV disclosure to all male primary sexual partners and
      wife was 41.8% (177/423) and 4.5% (19/423) respectively, 20.3% (86/423) of them
      disclosure to some of male primary partners and 37.8% (160/423) not disclosure to
      any male primary partners. Participants who had HIV-positive male partners in the
      past 6 months (accounting for 35.2% (149/423)) were more likely to disclose HIV
      infection to their primary sexual partners (70.5% (105/149)) than those who had
      non-HIV-positive sexual partners (26.3% (72/274)) (chi(2) = 77.46, P < 0.01).
      Participants who had male unknown HIV-status sexual partners in the past 6
      months(accounting for 52.7% (223/423)) were less likely to disclosure HIV
      infection to primary sexual partners (22.4% (50/223) ) than those who had already
      known HIV-status sexual partners (63.5% (127/200)) (chi(2) = 73.11, P < 0.01).
      The possibility of HIV disclosure to primary sexual partner among participants
      who had HIV-positive sexual partner increase to 6.36 (3.75-10.80) times of those
      who had HIV -negative partners, and the possibility among participants who had
      sexual partners of unknown HIV status decreased to 0.44 (0.25-0.76) times of
      those who had sexual partners of already known HIV status. Compared with having
      non-anal sex behaviors with male primary partner, the possibility of HIV
      disclosure to primary sexual partner decreased to 0.46 (0.22-0.95) times among
      participants who had anal sex behavior with male primary partners. CONCLUSION:
      There were low proportion of HIV disclosure to primary sexual partners among HIV
      infected MSM in Guangzhou, Chongqing and Chengdu.HIV disclosure to primary sexual
      partners may be associated with characteristics of their sexual partners, and
      participants who had HIV-positive male partners were more likely to disclose HIV
      infection to their primary sexual partners.

PMID- 25582368
TI  - [Study on gay identity status and its association with sexual behaviors among men
      who has sex with men in Xinjiang Uygur Autonomous Region].
AB  - OBJECTIVE: To investigate gay identity status of men who have sex with men(MSM)
      in Xinjiang, and analyze its association with sexual behaviors. METHODS: From May
      to August in 2013, an anonymous questionnaire survey with convenience sampling
      was conducted among MSM in Urumqi, Kashgar, Aksu and Yining cities of Xinjiang.
      Those who were >= 16 years of age and claimed to have male-to-male sex behaviors
      were eligible for the survey. A total of 1 467 participants were recruited. Chi
      square analysis was performed for examining the association between ego-identity,
      social-identity and relevant sexual behaviors. Selected variables associated with
      ego-identity, social-identity in the univariate analysis were subsequently
      assessed in a multivariate analysis using logistic regression. RESULTS: The MSM
      with positive ego-identity accounted for 44.7% (656/1 467), and positive social
      identity accounted for 29.1% (427/1 467). For ego-identity, Uyghur MSM were less
      positive than Han MSM (OR (95%CI) was 0.43 (0.32-0.58) ) ; those who were over 20
      years of age when accepting their sexual orientation were less positive than
      those who were younger than 20 years of age when accepting their sexual
      orientation (OR (95%CI) was 0.61 (0.47-0.80) );and homosexuals were more positive
      than bisexuals (OR (95%CI) was 1.98 (1.50-2.61) ). For social-identity, Hui MSM
      were less positive than Han MSM (OR (95%CI) was 0.61 (0.42-0.88) ); those whose
      education level was higher than college were less positive than those with junior
      high education (OR (95%CI) was 0.60 (0.40-0.89) ); famers/herdsmen were more
      positive than students (OR (95%CI) was 4.17 (2.13-8.17) ); the divorced/widowed
      were more positive than the singles (OR (95%CI) was 2.40 (1.34-4.29) ); those who
      were over 20 years of age when accepting their sexual orientation were less
      positive than those who were younger than 20 years of age when accepting their
      sexual orientation (OR (95%CI) was 0.59 (0.44-0.81) ). Among the MSM with
      negative ego-identity and negative social-identity, the proportion of planning to
      get married with women was 66.8% (267/400) and 76.5% (306/400), respectively,
      which were higher than those with positive ego-identity (33.2% (133/400)) and
      positive social-identity (23.5% (94/400)) ; their proportion of intending to have
      offspring was 62.0% (287/463) and 73.4% (340/463), respectively, which were
      higher than those with positive ego-identity and social-identity (38.0%
      (176/463), 26.6% (123/463)) (chi(2) = 39.61 and 7.90, respectively, both P values
      were <0.05). Among the MSM with negative social-identity, the proportion of
      looking for male sexual partners in toilets or parks was 18.1% (188/1 040), in
      bathhouse or sauna was 17.3% (180/1 040), and through internet was 82.0% (853/1
      040), which were higher than those with positive social-identity (8.9% (38/427),
      9.8% (42/427) and 61.6% (263/427)) (chi(2) = 66.78, P < 0.01). CONCLUSION: In
      2013, the gay identity of MSM in Xinjiang was relatively poor, and the factors
      associated with it included ethnicity, occupation, marital status and education
      level. The MSM with negative identity tended to involve in risk sexual behaviors,
      and had increased risk of HIV infection.

PMID- 25582369
TI  - [Infection status of HIV and its influence factors among men who have sex with
      men in Sichuan province].
AB  - OBJECTIVE: To investigate HIV infection status and its influence factors in men
      who have sex with men (MSM) in Sichuan province. METHODS: A face to face
      investigation and Syphilis and HIV serological detection were conducted among 2
      783 MSM who have the insertion of oral or anal sex with men over the past year
      recruited by snowball sampling and respondent driven sampling methods in nine
      cities' Gay venues of Sichuan province. chi(2) test and logistic regression
      analysis were used for statistical analysis. RESULTS: A total of 2 783 MSM were
      surveyed, of which HIV and Syphilis infection rates were 11.1% (147/2 783) , 5.3%
      (310/2 783) , respectively. The HIV infection rates of <20 year-old age group, 20
      29 year-old age group, 30-39 year-old age group, 40-49 year-old age group, >= 50
      year-old age group were 6.6% (15/227), 9.7% (143/1 471), 11.8% (80/679), 18.0%
      (53/294), 17.0% (19/112) (chi(2) = 25.91, P < 0.05). The risk of HIV infection in
      30-39 year-old age group, 40-50 year-old age group,> 50 years age group were 2.05
      (1.14-3.69) times, 3.24 (1.75-6.01) times, 2.60 (1.22-5.52) times respectively of
      the <20 years age group. The risk of HIV infection in middle school and below one
      was 16.5% (73/443) , higher than the high school/college education MSM (11.1%
      (99/891) ) and the college and higher education MSM (9.5% (138/1 446)) (chi(2) =
      16.46, P < 0.05). The risk of HIV infection in High school/college education MSM
      were 0.64 (0.45-0.90) times of the middle school and below. The HIV infection
      rates of MSM who accepted a HIV test and knew the result within the last year was
      8.2% (119/1 446) , lower than the group who did not accepted any HIV test (14.3%
      (191/1 336) ) (chi(2) = 25.81, P < 0.05). The HIV infection rates of MSM who
      received intervention services was 10.1% (256/2 539), lower than the group who
      did not receive any intervention services (22.1% (54/244) ) (chi(2) = 32.65, P <
      0.05) . The HIV infection rates of Syphilis-positive MSM was 32.0% (47/147) ,
      higher than the Syphilis-negative one (10.0% (263/2 636) ) (chi(2) = 68.06, P <
      0.05). Received intervention services (OR (95%CI) was 0.52 (0.40-0.68) ) and
      accepted a HIV test and knew the result within the last year (OR (95%CI) was 0.52
      (0.36-0.74) ) were the protective factors of HIV infection. At the same time, the
      syphilis infection (OR (95%CI) was 4.01 (2.73-5.88) ) were risk factors for HIV
      infection. CONCLUSION: The prevalence rates of HIV infections were considered to
      be high among MSM in Sichuan province. The MSM of low-literacy, 30 years or
      older, not received any intervention services, not received any intervention
      services.Syphilis-positive have a greater risk of HIV infection.

PMID- 25582370
TI  - [Study on risk factors of hepatitis C virus infection among Han population in
      Henan province].
AB  - OBJECTIVE: To study the risk factors of hepatitis C Virus Infection among Han
      population in Henan Province, providing evidence for the development of targeted
      prevention and control measures. METHODS: In this 1: 1 matched case-control
      study, data of 134 cases and 134 controls were collected in seven hospitals from
      June 2013 to September 2013. Case group with the following conditions: Han
      nationality, first diagnosed hepatitis C in 2013, Current address and
      investigation belong to the same district (county), above 18 years old; with the
      following conditions can't into case group: not to cooperate with the
      investigation, late-stage Hepatitis C patients. Control group with the following
      conditions: Han nationality, with the matched case patients the same gender, in
      the same hospital for treatment , from the same district (county), the age
      difference <= 5 years old and in the same age group. With the following
      conditions can't into control group:not to cooperate with the investigation,
      diagnosed with hepatitis B, hepatitis C patients. Collect 3 ml blood samples to
      test anti-HCV. Single factors were analyzed with chi(2) between case and control,
      risk factors were analyzed with logistic regression model. RESULTS: The ratio
      about blood donation, blood transfusion, operation and acupuncture of cases were
      35.1% (47/134), 27.6% (37/134), 42.5% (57/134), 12.7% (17/134), with differences
      compared to those of controls (2.2% (3/134), 5.2% (7/134), 21.6% (29/134), 5.2%
      (7/134))(chi(2) values were 47.60, 24.47, 13.42 and 4.58, all P values <0.05).
      Compared with those never received blood transfusion and those never donated
      blood, former blood receptors and blood donors had higher risk of hepatitis C
      infection(OR: 2.01, 95%CI:1.32-3.05; OR:2.68, 95%CI:1.85-3.88). RESULTS: of
      multiple nonconditional logistic regression analysis showed that Plasma donors
      and whole blood donors had higher risk of hepatitis C infection than those never
      donated plasma and blood (OR:76.71, 95%CI: 10.25-574.25; OR:10.23, 95%CI: 2.15
      48.70). CONCLUSION: Blood transfusion and abnormal blood are independent risk
      factors among Han population in Henan Province of hepatitis C infection. The
      Plasma donors, blood donors and with the increase in the times of blood
      transfusion, the risk of hepatitis C infection is increase.

PMID- 25582371
TI  - [Associations between vegetables and fruit intake and quality of life in breast
      cancer patients].
AB  - OBJECTIVE: To investigate the associations between vegetables and fruit intake
      and quality of life in breast cancer patients. METHODS: A total of 3 344
      community breast cancer patients were selected through cluster sampling method
      between April and July 2013, in Shanghai, China. Data were collected using a
      questionnaire, which included socio-demographic situation, cancer survival and
      health behaviors(i.e. vegetables or fruit intake, exercise), European
      Organization for Research and Treatment (EORTC) QLQ-C30 Simplified Chinese
      version(3rd edition) and Functional Assessment of Cancer Therapy scale (FACT-G)
      Simplified Chinese version(4th edition) were used to evaluate the quality of
      life. Crude quality of life scores were compared between groups. Multiple linear
      models were used to calculate and compare adjusted means of quality of life
      between groups, controlling relevant factors. RESULTS: After adjusting relevant
      factors, breast cancer patients who ate more than 250 g vegetables reported
      higher EORTC physical functioning scores, cognitive functioning scores, emotional
      functioning scores, global health scores than patients who ate equal or less than
      250 g vegetables(respectively (80.79 +/- 0.85) vs (79.34 +/- 0.82), (80.07 +/-
      1.03) vs (77.84 +/- 0.99), (84.17 +/- 0.95) vs (82.76 +/- 0.92), (65.75 +/- 1.50)
      vs (62.92 +/- 1.45)), t values respectively were 2.76, 3.54, 2.40, 3.17, all P
      values were <0.05; and breast cancer patients who ate more than 250 g vegetables
      reported higher FACT-G social well-being scores, function well-being scores, FACT
      G total scores than patients who ate equal or less than 250 g vegetables
      (respectively (17.92 +/- 0.40) vs (17.31 +/- 0.39), (14.86 +/- 0.42) vs (14.34 +/
      0.40), (74.78 +/- 1.01) vs (73.05 +/- 0.97)), t values respectively were 2.49,
      2.05, 2.90, all P values were <0.05. After adjusting relevant factors, breast
      cancer patients who ate fruit everyday reported higher EORTC physical functioning
      scores, role functioning scores, cognitive functioning scores, emotional
      functioning scores, social functioning scores, global health scores than patients
      who didn't eat fruit everyday (respectively (80.40 +/- 0.82) vs (79.22 +/- 0.87),
      (89.81 +/- 1.00) vs (88.06 +/- 1.05), (79.78 +/- 0.99) vs (77.11 +/- 1.04),
      (84.43 +/- 0.92) vs (81.56 +/- 0.97), (77.95 +/- 1.25) vs (75.56 +/- 1.31),
      (65.48 +/- 1.44) vs (61.74 +/- 1.51)), t values respectively were 2.15, 2.64,
      4.07, 4.71, 2.89, 4.02, all P values were <0.05; and breast cancer patients who
      ate fruit everyday reported higher FACT-G physical well-being scores, social well
      being scores, emotional well-being scores, functional well-being scores, FACT-G
      total scores than patients who didn't eat fruit everyday(respectively (23.35 +/-
      0.26) vs (22.85 +/- 0.28), (17.91 +/- 0.39) vs (16.98 +/- 0.41), (18.59 +/- 0.22)
      vs (18.18 +/- 0.23), (14.79 +/- 0.40) vs (14.17 +/- 0.42), (74.71 +/- 0.97) vs
      (72.17 +/- 1.02)), t values respectively were 2.92, 3.65, 2.91, 2.35, 4.05 , all
      P values were <0.05. CONCLUSION: There are active associations between vegetables
      / fruit intake and quality of life in breast cancer patients. Proper diet may
      help improve quality of life in breast cancer patients.

PMID- 25582372
TI  - [Evaluation of optimized sequential screening program of colorectal cancer in
      current China].
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of optimized sequential
      screening program of colorectal cancer, and provide evidence for the further
      optimization of colorectal cancer screening program. METHODS: Using cluster
      sampling method, 4 administrative villages were selected from Jiashan county as a
      census district in 2011 to 2013. Volunteers of 40 to 74 years old in the census
      were recruited, and tested by both optimized sequential screening (including
      questionnaire survey and fecal occult blood test) and colonoscopy for colorectal
      cancer. Sensitivity and specificity of different screening methods were
      calculated, respectively. RESULTS: A total of 2 607 volunteers took both
      simultaneously screening and colonoscopy at the same time. 20 colorectal cancer
      cases, 85 advanced adenoma cases, 271 non-advanced adenomas cases, and 141 non
      adenomatous polyps cases were detected. Sensitivity of optimized sequential
      screening for colorectal cancer, advanced adenomas, and non-advanced adenomas
      were 70.0% (14/20) , 57.6% (49/85) and 36.5% (99/271) , specificity was 68.7% (1
      776/2 587) , 69.2% (1 746/2 522) and 68.9% (1 610/2 336) , respectively.
      Sensitivity of the fecal occult blood test of colorectal cancer, advanced
      adenomas and non-advanced adenomas were 70.0% (14/20) , 47.1% (40/85) and 26.6%
      (72/271), specificity was 79.4% (2 053/2 587), 79.9% (2 014/2 522) and 79.6% (1
      860/2 336). The sensitivity of fecal occult blood test and those of optimized
      sequential screening for colorectal cancer, advanced adenomas was not significant
      (chi(2) = 0.00, 1.91, all P values > 0.05). Sensitivity of questionnaire survey
      of colorectal cancer, advanced adenomas and non-advanced adenomas were 10.0%
      (2/20), 14.1% (12/85), 12.9% (35/271), specificity was 87.6% (2 266/2 587), 87.7%
      (2 211/2 522), 87.6% (2 046/2 336). There were no significant difference between
      non-advanced adenomas. The sensitivity of advanced adenomas and non-advanced
      adenomas showed no significant decline when the following six term were removed
      from screening programs: chronic diarrhea, chronic constipation, mucus or bloody
      history, history of chronic appendicitis or appendectomy surgery, chronic
      cholecystitis or gallbladder surgery, adverse events in the history of life,
      while the sensitivity of colorectal cancer remained nearly the same 70.0%
      (14/20), 52.9% (45/85), 31.4% (85/271) (chi(2) = 0.38, 1.61, all P values >
      0.05). CONCLUSION: Current optimized sequential screening programs for colorectal
      cancer in China have a high sensitivity and specificity. However, further
      optimization is viable and necessary.

PMID- 25582373
TI  - [Occupational stress situation analysis of different types of train drivers].
AB  - OBJECTIVE: To analyze the status of occupational stress in different types of
      train drivers. METHODS: By using cluster sampling method, a cross-sectional study
      was conducted in 1 339 train drivers (including 289 passenger train drivers, 637
      freight trains drivers, 339 passenger shunting train drivers, and 74 high speed
      rail drivers) from a Railway Bureau depot. The survey included individual
      factors, occupational stress factors, stress response factors and stress
      mitigating factors. The occupational stress factors, stress response factors and
      mitigating factors were measured by the revised effort-reward imbalance (ERI)
      model questionnaires and occupational stress measurement scale. By using the
      method of covariance analysized the difference of occupational stress factors of
      all types train drivers, the method of Stepwise regression was used to analyze
      the effection (R(2)) of occupational stress factors and stress mitigating factors
      on stress response factors. RESULTS: Covariance analysis as covariates in age,
      education level, length of service and marital status showed that the scores of
      ERI (1.58 +/- 0.05), extrinsic effort (19.88 +/- 0.44), rewards (23.43 +/- 0.43),
      intrinsic effort (17.86 +/- 0.36), physical environment (5.70 +/- 0.22), social
      support (30.51 +/- 0.88) and daily tension (10.27 +/- 0.38 ) of high speed rail
      drivers were higher than other drivers (F values were 6.06, 11.32, 7.05, 13.25,
      5.20, 9.48 and 6.14 respectively, P < 0.01), but the scores of emotional balance
      (4.15 +/- 0.31) and positive emotion (2.06 +/- 0.20) were lower than other drives
      (P < 0.01);the scores of psychological needs (10.48 +/- 0.18), emotional balance
      (4.88 +/- 0.16) and positive emotion (2.63 +/- 0.10) of passenger train drivers
      were higher than other drivers (F values were 4.33 and 5.50 respectively, P <
      0.01). The descending rank of the effect value on occupational stress factors and
      mitigating factors to depressive symptoms of train drivers was high speed rail
      drivers (R(2) = 0.64), passenger train drivers (R(2) = 0.44), passenger shunting
      train drivers (R(2) = 0.39), freight trains drivers (R(2) = 0.38); job
      satisfaction of train drivers was high speed rail drivers (R(2) = 0.68),
      passenger train drivers (R(2) = 0.62), freight trains drivers (R(2) = 0.43),
      passenger shunting train drivers(R(2) = 0.38); to daily tension of train drivers
      was high speed rail drivers (R(2) = 0.54), passenger train drivers (R(2) = 0.37),
      passenger shunting train drivers (R(2) = 0.33), freight trains drivers (R(2) =
      0.30); emotional balance of train drivers was high speed rail drivers (R(2) =
      0.47), passenger train drivers (R(2) = 0.43), passenger shunting train drivers
      (R(2) = 0.33), freight trains drivers(R(2) = 0.31). CONCLUSION: ERI,
      psychological needs, work responsibilities, job roles, work conflict, and
      physical environment were important occupational stress factors of train drivers;
      social support was pivotal mitigating factors; different train drivers had
      different occupational stress status, high speed rail drivers were the highest,
      and freight trains drivers passenger train drivers or passenger shunting train
      drivers were the lowest.

PMID- 25582374
TI  - [Protective effects of sulforaphane on the oxidative damage of kidney
      mitochondria complex in obese rats induced by high-fat diet].
AB  - OBJECTIVE: To realize the oxidative damage of kidney mitochondrial complex in
      obese rats induced by high-fat diet and investigate the protective effects of
      sulforaphane against the damage. METHODS: Eighty-eight adult male SD rats were
      used, after 1 week adaptability feeding, 8 rats were selected as control group
      and given low-fat diet. The other 80 rats were given high-fat diet. After 2
      weeks, the 32 diet-induced obesity models were choosen whose weight gain was
      higher than 40%. The 32 rats were randomly divided into 4 groups, i.e. high fat
      group, high fat+sulforaphane low dose group, high fat+sulforaphane middle dose
      group and high fat+sulforaphane high dose group. The rats in the sulforaphane
      low, middle and high dose groups were orally administered with sulforaphane 5, 10
      and 20 mg/kg, all the 4 groups were kept feeding high-fat diet for 5 weeks. All
      rats were sacrificed and their kidneys were removed to assay the index of
      oxidative damages. RESULTS: The content of ROS (0.26 +/- 0.04) and MDA((0.87 +/-
      0.05) U/mg) in the hight-fat group were significantly higher than those in the
      control group((0.20 +/- 0.02),(0.57 +/- 0.08) U/mg)(t values were -3.02 and 
      4.72, P < 0.05). The activity of T-AOC((0.43 +/- 0.04) U/mg) and MMP (12.09 +/-
      1.56) were lower than the control group ((0.48 +/- 0.04 U/mg, (16.08 +/- 3.12)
      )(t values were 2.06 and 2.28, P < 0.05). Gavage intervention with sulforaphane,
      the MDA amount ((0.67 +/- 0.05), (0.55 +/- 0.05), (0.56 +/- 0.07) U/mg) in the
      sulforaphane low, middle and high dose groups were lower than the hight-fat group
      ((0.87 +/- 0.05) U/mg (t values were 3.65, 5.71 and 5.60. P < 0.05). The activity
      of T-AOC ((0.49 +/- 0.05), (0.55 +/- 0.05), (0.54 +/- 0.04) U/mg), T-SOD ((61.07
      +/- 2.79), (55.95 +/- 2.39), (60.26 +/- 6.02) U/mg) and the level of MMP ((17.17
      +/- 2.52), (18.24 +/- 2.54), (18.21 +/- 3.65)) were higher than in the high-fat
      group ((0.43 +/- 0.04) U/mg,(47.22 +/- 2.43) U/mg,(12.09 +/- 1.56)) (tT-AOC
      values were -2.36, -4.83 and -4.30; tT-SOD values were -6.37, -4.71 and -5.99;
      tMMP values were -2.90, -3.52 and -3.50, P < 0.05). The activity of GSH-Px in the
      sulforaphane low and middle dose groups ((69.12 +/- 8.63), (64.43 +/- 6.58) U/mg)
      were higher than those in the high-fat group((53.03 +/- 5.70) U/mg)(t values were
      -3.82 and -2.71, P < 0.05). But there were no significant difference between the
      high dose group ((60.02 +/- 7.05) U/mg) and the high-fat group (t = -1.66, P >
      0.05). CONCLUSION: High-fat diet can induce the mitochondrial oxidative
      dysfunction in kidney, and sulforaphane shows protective effect on the kidney
      mitochondrial complex from oxidative damage in obese rats induced by high-fat
      diet.

PMID- 25582375
TI  - Delivery aspects of antioxidants in diabetes management.
AB  - INTRODUCTION: Ample research has been done to study the role of oxidative stress
      due to the generation of excess reactive species in initiation and progression of
      diabetic complications. A positive result has been indicated hypothesizing that
      abating this oxidative stress can prove to be an alternate strategy in therapy
      apart from oral antidiabetic drugs. But these dietary antioxidants are less
      efficient because of poor solubility, permeability, instability on storage,
      gastrointestinal degradation and first-pass metabolism. AREAS COVERED: This
      review gives a brief insight into the molecular mechanism of oxidative stress in
      development of diabetic complications. Major hurdles limiting the translation of
      antioxidants to clinical area are also discussed. Various delivery approaches
      including both conventional and novel drug delivery systems explored so far for
      combating these challenges in antioxidant delivery are also explored.
      Mitochondrial targeting of such molecules is also briefly discussed. EXPERT
      OPINION: A thorough study of clinical efficacy and safety of antioxidants on long
      term use judging its clinical applicability is required. The clinical success of
      antioxidants as a therapeutic strategy involves a combination of effective design
      of drug delivery carrier that are in turn related to their degradation profile,
      possibility of cellular uptake at defined site of action and so on and clinical
      and preclinical trials that will provide a base for the design of dose and
      administration regimen.

PMID- 25582376
TI  - Using a randomised controlled trial (RCT) methodology in CAM research with
      gynaecological cancer patients: A commentary on the perks and pitfalls.
AB  - This paper provides a commentary on several challenges faced by researchers when
      conducting randomised controlled trials (RCTs) utilising complementary therapies
      with cancer patients. Several factors, such as research design and recruitment to
      the intervention are discussed. Examples are drawn from an RCT conducted by the
      lead author regarding the use of yoga to improve the quality of life of
      gynaecological cancer patients undergoing treatment for their cancer. This paper
      gives methodological insights into some of the difficulties experienced when
      conducting research with cancer patients, and provides a number of
      recommendations based on the available evidence and practical application of
      these methods.

PMID- 25582377
TI  - Failure of atovaquone-proguanil malaria chemoprophylaxis in a traveler to Ghana.
AB  - Clinical failure of MalaroneTM chemoprophylaxis is extremely rare. We report a
      case of Plasmodium falciparum malaria in a returned traveler to Ghana who fully
      adhered to atovaquone-proguanil (MalaroneTM) chemoprophylaxis daily dosing, yet
      took the pills on an empty stomach. Screening of the P. falciparum isolate
      revealed triple codon mutation of Dhfr at positions 51, 59, and 108. Plasma drug
      levels of both atovaquone and proguanil revealed sub-therapeutic concentrations. 

PMID- 25582378
TI  - Comparison of different irrigation activation techniques on smear layer removal:
      an in vitro study.
AB  - The purpose of this study was to evaluate the efficiency of different irrigation
      activation techniques on smear layer removal. About 80 single-rooted human
      maxillary central teeth were decoronated to a standardized length.The samples
      were prepared by using ProTaper system to size F4 and divided into eight equal
      groups (n = 10) according to the final irrigation activation technique; distilled
      water was used as an irrigant in Group 1. The other groups were treated with 2.5%
      NaOCl and 17% EDTA, respectively. Conventional syringe irrigation (CSI) was used
      in Group 2. Irrigation solutions were activated using passive ultrasonic
      irrigation (PUI, Group 3), EndoVac apical negative pressure (ANP, Group 4), diode
      laser (Group 5), Nd:YAG laser (Group 6), Er:YAG laser (Group 7), and Er:YAG laser
      using with photon-induced photoacoustic streaming (PIPSTM, Group 8). Teeth were
      split longitudinally and subjected to scanning electron microscope (SEM). PIPS
      showed the best removal of smear layer when compared with PUI, ANP, Nd:YAG, and
      Er:YAG, but the difference was not statistically significant (P > 0.05). Smear
      layer scores obtained with PIPS technique were statistically significant
      different from those of obtained with control, CSI and diode laser groups (P <
      0.05). All experimental irrigation techniques except ANP and diode laser removed
      smear layer more effectively at the coronal and middle levels compared to the
      apical level (P < 0.05). Irrigation activated/delivered techniques except diode
      laser have a positive effect on removing of smear layer.

PMID- 25582379
TI  - gamma-PGA-coated mesoporous silica nanoparticles with covalently attached
      prodrugs for enhanced cellular uptake and intracellular GSH-responsive release.
AB  - Poor cellular uptake of drug delivery carriers and uncontrolled drug release
      remain to be the major obstacles in cancer therapy due to their low delivery
      efficiency. In this study, a multifunctional intracellular GSH (glutathione)
      responsive silica-based drug delivery system with enhanced cellular uptake
      capability is developed. Uniform 50 nm colloidal mesoporous silica nanoparticles
      (MSNs) with mercaptopropyl-functionalized core and silanol-contained silica
      surface (MSNs-SHin ) are designed and fabricated as a platform for drug covalent
      attachment and particle surface modification. Doxorubicin (DOX) with primary
      amine group as an anticancer model drug is covalently conjugated to the mesopores
      of MSNs-SHin via disulfide bonds in the presence of a heterobifunctional linker
      (N-Succinimidyl 3-(2-pyridyldithio) propionate). Poly(gamma-glutamic acid) (gamma
      PGA) can be coated onto the particle surface by sequential electrostatic
      adsorption of polyethyleneimine (PEI) and gamma-PGA. The constructed delivery
      system exhibits enhanced cellular uptake via a speculated gamma-glutamyl
      transpeptidase (GGT)-mediated endocytosis pathway and controlled drug release
      capacity via intracellular GSH-responsive disulfide-bond cleavage, and thus
      significantly inhibits the growth of cancer cells. The multifunctional delivery
      system paves a new way for developing high-efficient particle-based
      nanotherapeutic approach for cancer treatment.

PMID- 25582380
TI  - Re: Can magnetic resonance-ultrasound fusion biopsy improve cancer detection in
      enlarged prostates?: A. Walton Diaz, A. N. Hoang, B. Turkbey, C. W. Hong, H.
      Truong, T. Sterling, S. Rais-bahrami, M. M. Siddiqui, L. Stamatakis, S.
      Vourganti, J. Nix, J. Logan, C. Harris, M. Weintraub, C. Chua, M. J. Merino, P.
      Choyke, B. J. Wood and P. A. Pinto J Urol 2013; 190: 2020-2025.

PMID- 25582381
TI  - Photocontrol of ion permeation in lipid vesicles with amphiphilic
      dithienylethenes.
AB  - The integration of photochromic dithienylethenes (DTEs) with lipid vesicles as
      photoresponsive membrane disruptors for ion transport applications has been
      examined. We have synthesized three amphiphilic DTEs 1-3 that incorporate a
      terminally charged alkyl chain, and contain methyl or phenylethynyl substituents
      at the reactive carbons. Our photochromic reactivity studies suggest that the
      inclusion of a single alkyl chain favors the photoactive antiparallel
      conformation of DTEs, given the significant improvement in the cyclization
      quantum yield over previous phenylethynyl derivatives. Our ion permeation studies
      show that the open-ring isomers of these DTEs are more disruptive than the closed
      ring isomers in the four lipid vesicle systems studied, regardless of their
      lamellar phase at room temperature. In addition, a steric effect was clearly
      observed as DTEs incorporating the comparatively smaller methyl group exhibited
      lower rates of ion permeation than the bulkier phenylethynyl group. In all cases,
      UV irradiation led to a reduction in ion permeability. In fact, the methyl analog
      exhibited a significant reduction in ion permeability in gel-phase lipid vesicles
      upon UV exposure. Also, the hexyl chain derivatives had a greater effect on
      membrane permeability than the dodecyl derivative owing to their relative
      position in the bilayer membrane of lipid vesicles.

PMID- 25582383
TI  - Prognostic significance of ligands belonging to tumour necrosis factor
      superfamily in acute lymphoblastic leukaemia.
AB  - Altered activities of ligands belonging to tumour necrosis factor (TNF)
      superfamily, namely B-cell activating factor (BAFF), a proliferation-inducing
      ligand (APRIL) and apoptosis inducing ligand (TRAIL) were demonstrated in several
      haematological diseases including acute lymphoblastic leukaemia (ALL). BAFF,
      APRIL and TRAIL provide crucial survival signals to immature, naive and activated
      B cells. These ligands are capable of activating a broad spectrum of
      intracellular signalling cascades that can either induce apoptosis or protect
      from programmed cell death. BAFF and APRIL, which can directly activate the NF
      kappaB pathway, have been identified as crucial survival factors for ALL cells.
      Here, we have analyzed serum BAFF, APRIL and TRAIL concentrations in 48 patients
      with newly diagnosed ALL and 44 healthy volunteers. The levels of APRIL and BAFF
      were significantly higher in ALL patients as compared to healthy volunteers. In
      contrast, concentrations of TRAIL were significantly lower in ALL patients.
      Moreover, following induction, the levels of APRIL, but not BAFF or TRAIL, were
      significantly lower in a group of patients with complete remission (CR) as
      compared to non-respondent (NR) ALL patients. Furthermore, we demonstrated
      statistically significant differences in concentrations of APRIL between CR MRD
      negative and CR, MRD-positive ALL patients. Notably detection of higher
      concentrations of APRIL was associated with shorter leukaemia-free survival and
      overall survival. Altogether, our data indicate that APRIL can play an important
      role in the pathogenesis of ALL and the measurement of APRIL levels can improve
      prognostication in ALL patients.

PMID- 25582382
TI  - Clinical Measures of Disease Progression in Amyotrophic Lateral Sclerosis.
AB  - Progressive weakness remains the clinical hallmark of amyotrophic lateral
      sclerosis (ALS). Accordingly, a variety of tools has been developed to capture
      this disease feature, including questionnaires, such as the ALS-functional rating
      scale, strength testing, pulmonary function tests, electrophysiologic measures,
      including motor unit number estimation, and imaging techniques. Despite this
      plethora of approaches, there is little agreement as to what measures to use in a
      given clinical trial or in the clinic during routine patient care. Part of the
      reason for this uncertainty is that ALS is a remarkably protean disease. Some
      individuals progress rapidly, others slowly; some patients have considerable
      upper motor neuron dysfunction, whereas others have little; and there is
      considerable variation in the sequence of body regions affected, in some the
      disease beginning in the bulbar musculature and in others in one arm or one leg.
      Here, I present a variety of basic and more complex clinical measures for
      potential use in therapeutic trials with the aim of offering a balanced and
      practical set of recommendations, as well as considerations for future studies. 

PMID- 25582384
TI  - The impact of sensitive KIT D816V detection on recognition of indolent Systemic
      Mastocytosis.
AB  - Patients with Systemic Mastocytosis (SM) need a highly sensitive diagnostic test
      for D816V detection of the KIT receptor gene. Along with histology/cytology and
      flow cytometry evaluation, bone marrow (BM) from 110 consecutive adult patients
      referred with a suspicion of SM to Multidisciplinary Outpatient Clinic for
      Mastocytosis in Verona were tested both by Amplification Refractory Mutation
      System Reverse Transcriptase quantitative real time Polymerase Chain Reaction
      (ARMS-RT-qPCR) and RT-PCR+Restriction Fragment Length Polymorphism (RFLP)
      followed by Denaturing-High Performance Liquid Chromatography (D-HPLC) and Sanger
      sequencing. ARMS-RT-qPCR identified D816V mutation in 77 patients, corresponding
      to 100% of cases showing CD25(+) mast cells (MCs) whereas RT-PCR+RFLP/D
      HPLC+sequencing revealed D816V mutations in 47 patients. According to the 2008
      WHO criteria 75 SM, 1 Cutaneous Mastocytosis (CM), 1 monoclonal MC activation
      syndrome (MMAS), and 1 SM Associated with Haematologic Non-Mast Cell Disorder (SM
      AHNMD) were diagnosed. Seventeen out 75 SM patients (23%) would have not
      satisfied sufficient WHO criteria on the basis of the sole RT-PCR+RFLP: these
      patients had significantly lower serum tryptase levels and amount of CD25(+) MCs.
      Therefore, ARMS-RT-qPCR might result particularly useful, in patients that do not
      fulfil major BM histological criterion, for the recognition of indolent SM with a
      very low MC burden. 

PMID- 25582385
TI  - Expression of CD44 and CD35 during normal and myelodysplastic erythropoiesis.
AB  - Erythroid dysplasia is a common feature of myelodysplastic syndromes (MDS).
      Currently available information about the immunophenotypic features of normal and
      dysplastic erythropoiesis is scarce and restricted to relatively few markers.
      Here we studied the expression of CD117, CD35 and CD44 throughout the normal
      (n=16) and dysplastic (n=48) bone marrow erythroid maturation. CD35 emerged as an
      early marker of CD34(+) erythroid-committed precursors, which is expressed before
      CD105 and remains positive thereafter. MDS patients (with and without morphologic
      dyserythropoiesis) displayed overall increased expression of CD44, associated
      with slight alterations on CD35 expression, suggesting that phenotypic
      alterations in MDS may precede morphologic dysplasia. In turn, MDS patients with
      anemia showed increased expression of CD117. 

PMID- 25582387
TI  - A general method for the fabrication of graphene-nanoparticle hybrid material.
AB  - We describe a simple and general approach to conjugate nanoparticles on pristine
      graphene. The method takes advantage of the high reactivity of perfluorophenyl
      nitrene towards the C[double bond, length as m-dash]C bonds in graphene, where
      perfluorophenyl azide-functionalized nanoparticles are conjugated to pristine
      graphene through the [2+1] cycloaddition reaction by a fast photoactivation. 

PMID- 25582386
TI  - A simple and sensitive LC-MS/MS method for the determination of sotalol in rat
      plasma.
AB  - A sensitive, rapid and robust HPLC method with tandem mass spectrometry
      (HPLC/MS/MS) detection has been developed and validated for the quantification of
      sotalol in rat plasma. Plasma samples were precipitated with acetonitrile before
      analysis. The chromatographic separation was performed on an Atlantis hydrophilic
      interaction liquid chromatography Silica column (50 * 2.1 mm, 3 um) with a
      gradient mobile phase of 10 mm NH4 COOH (containing 0.2% of formic acid) as
      buffer A and acetonitrile as mobile phase B. Sotalol (m/z 273.2 -> 255.1) and
      atenolol (the internal standard, IS, m/z 267.2 -> 190.1) were monitored under
      positive ionization mode with 5500 QTRAP. Retention time of sotalol and the IS
      were 2.69 and 3.43 min, respectively. The linear range was 5-500 nm based on the
      analysis of 0.1 mL of plasma. The intrabatch precision ranged from 1.2 to 6.1%,
      and the inter-batch precision was from 3.3 to 6.5%. The coefficient of variation
      of IS-normalized matrix factor was 7.6%. Experiments for stability were performed
      and the analyte was sufficiently stable. A run time of 6 min for each injection
      made it possible to analyze a high throughput of plasma samples. The assay was
      successfully applied to the determination of sotalol in rat plasma after a micro
      dose oral administration.

PMID- 25582388
TI  - Transdermal alcohol concentration data collected during a contingency management
      program to reduce at-risk drinking.
AB  - BACKGROUND: Recently, we demonstrated that transdermal alcohol monitors could be
      used in a contingency management procedure to reduce problematic drinking; the
      frequency of self-reported heavy/moderate drinking days decreased and days of no
      to low drinking increased. These effects persisted for three months after
      intervention. In the current report, we used the transdermal alcohol
      concentration (TAC) data collected prior to and during the contingency management
      procedure to provide a detailed characterization of objectively measured alcohol
      use. METHODS: Drinkers (n=80) who frequently engaged in risky drinking behaviors
      were recruited and participated in three study phases: a 4-week Observation phase
      where participants drank as usual; a 12-week Contingency Management phase where
      participants received $50 each week when TAC did not exceed 0.03g/dl; and a 3
      month Follow-up phase where self-reported alcohol consumption was monitored.
      Transdermal monitors were worn during the first two phases, where each week they
      recived $105 for visiting the clinic and wearing the monitor. Outcomes focused on
      using TAC data to objectively characterize drinking and were used to classify
      drinking levels as either no, low, moderate, or heavy drinking as a function of
      weeks and day of week. RESULTS: Compared to the Observation phase, TAC data
      indicated that episodes of heavy drinking days during the Contingency Management
      phase were reduced and episodes of no drinking and low to moderate drinking
      increased. CONCLUSIONS: These results lend further support for linking
      transdermal alcohol monitoring with contingency management interventions.
      Collectively, studies to date indicate that interventions like these may be
      useful for both abstinence and moderation-based programs.

PMID- 25582390
TI  - Multiple-tracer tests for contaminant transport process identification in
      saturated municipal solid waste.
AB  - Two column tests were performed in conditions emulating vertical flow beneath the
      leachate table in a biologically active landfill to determine dominant transport
      mechanisms occurring in landfills. An improved understanding of contaminant
      transport process in wastes is required for developing better predictions about
      potential length of the long term aftercare of landfills, currently measured in
      timescales of centuries. Three tracers (lithium, bromide and deuterium) were
      used. Lithium did not behave conservatively. Given that lithium has been used
      extensively for tracing in landfill wastes, the tracer itself and the findings of
      previous tests which assume that it has behaved conservatively may need
      revisiting. The smaller column test could not be fitted with continuum models,
      probably because the volume of waste was below a representative elemental volume.
      Modelling compared advection-dispersion (AD), dual porosity (DP) and hybrid AD-DP
      models. Of these models, the DP model was found to be the most suitable. Although
      there is good evidence to suggest that diffusion is an important transport
      mechanism, the breakthrough curves of the different tracers did not differ from
      each other as would be predicted based on the free-water diffusion coefficients.
      This suggested that solute diffusion in wastes requires further study. 

PMID- 25582391
TI  - Physical and numerical modeling of an inclined three-layer (silt/gravelly
      sand/clay) capillary barrier cover system under extreme rainfall.
AB  - As an extension of the two-layer capillary barrier, a three-layer capillary
      barrier landfill cover system is proposed for minimizing rainfall infiltration in
      humid climates. This system consists of a compacted clay layer lying beneath a
      conventional cover with capillary barrier effects (CCBE), which is in turn
      composed of a silt layer sitting on top of a gravelly sand layer. To explore the
      effectiveness of the new system in minimizing rainfall infiltration, a flume
      model (3.0 m * 1.0 m * 1.1 m) was designed and set up in this study. This
      physical model was heavily instrumented to monitor pore water pressure,
      volumetric water content, surface runoff, infiltration and lateral drainage of
      each layer, and percolation of the cover system. The cover system was subjected
      to extreme rainfall followed by evaporation. The experiment was also back
      analyzed using a piece of finite element software called CODE_BRIGHT to simulate
      transient water flows in the test. Based on the results obtained from various
      instruments, it was found that breakthrough of the two upper layers occurred for
      a 4-h rainfall event having a 100-year return period. Due to the presence of the
      newly introduced clay layer, the percolation of the three-layer capillary barrier
      cover system was insignificant because the clay layer enabled lateral diversion
      in the gravelly sand layer above. In other words, the gravelly sand layer changed
      from being a capillary barrier in a convention CCBE cover to being a lateral
      diversion passage after the breakthrough of the two upper layers. Experimental
      and back-analysis results confirm that no infiltrated water seeped through the
      proposed three-layer barrier system. The proposed system thus represents a
      promising alternative landfill cover system for use in humid climates.

PMID- 25582389
TI  - Ventricular conduction defects and the risk of incident heart failure in the
      Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND: We evaluated the risk of incident heart failure (HF) associated with
      various categories of ventricular conduction defects (VCDs) and examined the
      impact of QRS duration on the risk of HF. METHODS AND RESULTS: This analysis
      included 14,478 participants from the Atherosclerosis Risk in Communities (ARIC)
      study who were free of HF at baseline. VCDs (n = 377) were categorized into right
      and left bundle branch blocks (RBBB and LBBB, respectively), bifascicular BBB
      (RBBB with fascicular block), indeterminate-type VCD (IVCD), and pooled VCD group
      excluding lone RBBB. During an average of 18 years' follow-up, 1,772 participants
      were hospitalized for incident HF. Compared with no VCD, LBBB and pooled VCD were
      strongly associated with increased risk of incident HF (multivariable hazard
      ratios 2.87 and 2.29, respectively). Compared with no VCD with QRS duration <100
      ms, HF risk was 1.17-fold for the no VCD group with QRS duration 100-119 ms, 1.97
      fold for the pooled VCD group with QRS duration 120-139 ms, and 3.25-fold for the
      pooled VCD group with QRS duration >=140 ms. HF risk for the pooled VCD group
      remained significant (1.74-fold for QRS duration 120-139 ms and 2.81-fold for QRS
      duration >=140 ms) in the subgroup free from cardiovascular disease at baseline.
      Lone RBBB was not associated with incident HF. CONCLUSIONS: VCDs except for
      isolated RBBB are strong predictors of incident HF, and HF risk is further
      increased as the QRS duration is prolonged >140 ms.

PMID- 25582392
TI  - Zn(2+)-dependence of the synergistic increase in rat thymocyte cell lethality
      caused by simultaneous application of 4,5-dichloro-2-octyl-4-isothiazolin-3-one
      (DCOIT) and H2O2.
AB  - 4,5-Dichloro-2-octyl-4-isothiazolin-3-one (DCOIT) is an antifouling agent that is
      an alternative to organotins such as tributyltin (TBT). Because DCOIT decreases
      catalase activity, it may increase the susceptibility of cells to oxidative
      stress. We examined the effects of DCOIT on rat thymocytes suffering from
      oxidative stress induced by H2O2. The simultaneous application of DCOIT and H2O2
      induced a synergistic increase in cell lethality that was completely suppressed
      by chelating intracellular Zn(2+). Intracellular Zn(2+) concentration was
      increased by DCOIT at concentrations ranging from 0.1 MUM to 3 MUM. Although the
      increase in cell lethality produced by DCOIT alone was less than that produced by
      TBT alone, a synergistic increase was not induced by the combination of TBT and
      H2O2. Therefore, these results suggest that DCOIT increases vulnerability to
      oxidative stress and is more cytotoxic than TBT when oxidative stress is induced
      by H2O2.

PMID- 25582393
TI  - Impacts of coagulation on the adsorption of organic micropollutants onto powdered
      activated carbon in treated domestic wastewater.
AB  - The application of powdered activated carbon (PAC) as an advanced wastewater
      treatment step for the removal of organic micropollutants (OMP) necessitates
      complete separation of the PAC particles, e.g. by coagulation. In this study,
      potential positive or negative indirect or direct effects of coagulation on the
      adsorption of OMPs onto PAC in treated wastewater were investigated. Although the
      concentration of dissolved organic matter (DOM) was significantly reduced by
      coagulation, the selective removal of mainly larger DOM components such as
      biopolymers and humic substances did not improve subsequent OMP adsorption onto
      PAC, demonstrating that coagulation has minor effects on DOM constituents that
      are relevant for direct competition or pore blocking. The combination of
      coagulation and adsorption yielded the sum of the individual removals, as
      adsorption predominantly affected smaller compounds. While the formation of flocs
      led to visible incorporation of PAC particles, no significant mass transfer
      limitations impeded the OMP adsorption. As a result, the dosing sequence of
      coagulant and PAC is not critical for efficient adsorption of OMPs onto PAC. The
      relationships between adsorptive OMP removal and corresponding reduction of UV
      absorption at 254 nm (UVA254) as a promising surrogate correlation for the real
      time monitoring and PAC adjustment were affected by coagulation, leading to
      individual correlations depending on the water composition. Correcting for UVA254
      reduction by coagulation produces adsorptive UVA254 removal, which correlates
      highly with OMP removal for different WWTP effluents and varying coagulant doses
      and can be applied in combined adsorption/coagulation processes to predict OMP
      removal and control PAC dosing.

PMID- 25582399
TI  - A rare three-coordinated zinc cluster-organic framework with two types of
      secondary building units.
AB  - A rare chiral 3D cluster-organic framework {[Zn17O5(NTB)6(NDB)3].41H2O}n ()
      (H3NTB = 4,4',4''-nitrilotrisbenzoic acid and H2NDB = 4,4'-nitrilodibenzoic acid)
      was prepared and structurally characterized. Complex contains two types of
      [Zn4(MU4-O)(COO)6] and unreported [Zn9(MU3-O)3(COO)12] SBUs, which link bi- and
      tri-carboxylic acids and extend to an unprecedented (3,6,12)-connected framework.
      In addition, electronic structure calculations were performed to scrutinize the
      features of embedded clusters. 

PMID- 25582398
TI  - Clinical predictors of effective continuous positive airway pressure in patients
      with obstructive sleep apnea/hypopnea syndrome.
AB  - OBJECTIVES/HYPOTHESIS: To identify standard clinical parameters that may predict
      the optimal level of continuous positive airway pressure (CPAP) in adult patients
      with obstructive sleep apnea/hypopnea syndrome (OSAHS). STUDY DESIGN: This is a
      retrospective study in a tertiary academic medical center that included 129 adult
      patients (117 males and 12 females) with OSAHS confirmed by diagnostic
      polysomnography (PSG). METHODS: All OSAHS patients underwent successful full
      night manual titration to determine the optimal CPAP pressure level for OSAHS
      treatment. The PSG parameters and completed physical examination, including body
      mass index, tonsil size grading, modified Mallampati grade (also known as updated
      Friedman's tongue position [uFTP]), uvular length, neck circumference, waist
      circumference, hip circumference, thyroid-mental distance, and hyoid-mental
      distance (HMD) were recorded. RESULTS: When the physical examination variables
      and OSAHS disease were correlated singly with the optimal CPAP pressure, we found
      that uFTP, HMD, and apnea/hypopnea index (AHI) were reliable predictors of CPAP
      pressures (P = .013, P = .002, and P < .001, respectively, by multiple
      regression). When all important factors were considered in a stepwise multiple
      linear regression analysis, a significant correlation with optimal CPAP pressure
      was formulated by factoring the uFTP, HMD, and AHI (optimal CPAP pressure = 1.01
      uFTP + 0.74 HMD + 0.059 AHI - 1.603). CONCLUSIONS: This study distinguished the
      correlation between uFTP, HMD, and AHI with the optimal CPAP pressure. The
      structure of the upper airway (especially tongue base obstruction) and disease
      severity may predict the effective level of CPAP pressure. LEVEL OF EVIDENCE: 4.

PMID- 25582400
TI  - PET(CO2) measurement and feature extraction of capnogram signals for extubation
      outcomes from mechanical ventilation.
AB  - Capnography is a continuous and noninvasive method for carbon dioxide (CO2)
      measurement, and it has become the standard of care for basic respiratory
      monitoring for intubated patients in the intensive care unit. In addition, it has
      been used to adjust ventilatory parameters during mechanical ventilation (MV).
      However, a substantial debate remains as to whether capnography is useful during
      the process of weaning and extubation from MV during the postoperative period.
      Thus, the main objective of this study was to present a new use for time-based
      capnography data by measuring the end-tidal CO2 pressure ([Formula: see text]),
      partial pressure of arterial CO2 ([Formula: see text]) and feature extraction of
      capnogram signals before extubation from MV to evaluate the capnography as a
      predictor of outcome extubation in infants after cardiac surgery. Altogether, 82
      measurements were analysed, 71.9% patients were successfully extubated, and 28.1%
      met the criteria for extubation failure within 48 h. The ROC-AUC analysis for
      quantitative measure of the capnogram showed significant differences (p < 0.001)
      for: expiratory time (0.873), slope of phase III (0.866), slope ratio (0.923) and
      ascending angle (0.897). In addition, the analysis of [Formula: see text] (0.895)
      and [Formula: see text] (0.924) obtained 30 min before extubation showed
      significant differences between groups. The [Formula: see text] mean value for
      success and failure extubation group was 39.04 mmHg and 46.27 mmHg, respectively.
      It was also observed that high CO2 values in patients who had returned MV was
      82.8  +/-  21 mmHg at the time of extubation failure. Thus, [Formula: see text]
      measurements and analysis of features extracted from a capnogram can
      differentiate extubation outcomes in infant patients under MV, thereby reducing
      the physiologic instability caused by failure in this process.

PMID- 25582401
TI  - Facial asymmetry and genetic ancestry in Latin American admixed populations.
AB  - Fluctuating and directional asymmetry are aspects of morphological variation
      widely used to infer environmental and genetic factors affecting facial
      phenotypes. However, the genetic basis and environmental determinants of both
      asymmetry types is far from being completely known. The analysis of facial
      asymmetries in admixed individuals can be of help to characterize the impact of a
      genome's heterozygosity on the developmental basis of both fluctuating and
      directional asymmetries. Here we characterize the association between genetic
      ancestry and individual asymmetry on a sample of Latin-American admixed
      populations. To do so, three-dimensional (3D) facial shape attributes were
      explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual
      ancestry and heterozygosity was estimated using more than 730,000 genome-wide
      markers. Multivariate techniques applied to geometric morphometric data were used
      to evaluate the magnitude and significance of directional and fluctuating
      asymmetry (FA), as well as correlations and multiple regressions aimed to
      estimate the relationship between facial FA scores and heterozygosity and a set
      of covariates. Results indicate that directional and FA are both significant, the
      former being the strongest expression of asymmetry in this sample. In addition,
      our analyses suggest that there are some specific patterns of facial asymmetries
      characterizing the different ancestry groups. Finally, we find that more
      heterozygous individuals exhibit lower levels of asymmetry. Our results highlight
      the importance of including ancestry-admixture estimators, especially when the
      analyses are aimed to compare levels of asymmetries on groups differing on
      socioeconomic levels, as a proxy to estimate developmental noise.

PMID- 25582402
TI  - Phenotypic activation and pharmacological outcomes of spontaneously
      differentiated human monocyte-derived macrophages.
AB  - Macrophage activation has been observed in vivo under physiological and
      pathological conditions, and may represent an attractive target for
      pharmacological modulation. This study tested the hypothesis that human blood
      derived macrophages generated in vitro in the absence of specific macrophage
      growth factors respond flexibly to activation stimuli and pharmacological
      treatment. Monocytes were differentiated to macrophages for 7 days in culture in
      RPMI 1640 with 10% FCS. The resulting population showed predominance of the M2
      over M1 phenotype as measured by flow cytometry and the expression of M1 vs. M2
      markers was not mutually exclusive. Activation with LPS/IFN-gamma for 48 h
      significantly increased the fraction of surface CD68-expressing cells, the
      CD14(+)/CD16(-)/CD68(+) subset and cell-bound TNF-alpha levels, whereas
      expression of the CC chemokine receptor (CCR)-2 was unchanged. Expression of the
      M2 markers CD206, CD163 and CX3CR1 was down-regulated following M1 activation
      compared with resting and after pre-exposure to M2-triggers. By contrast,
      alternative activation with IL-4/IL-13 for 48 h did not increase M2 markers,
      while CD206 up-regulation was observed after 7 days. Both activation signals
      induced changes in gene expression profiles as shown by Q-PCR. Treatment with 100
      nM dexamethasone enhanced the M2 morphotype and CD163 expression while preventing
      LPS/IFN-gamma-induced CD163 down-regulation. After 1-week dexamethasone
      treatment, virtually all cells acquired a CD163(+)/CD206(+)/CX3CR1(+) M2
      phenotype. Therefore, these protocols appear to be useful to perform screens of
      pharmacological agents targeting human macrophage activation.

PMID- 25582404
TI  - Congenital combined deficiency of coagulation factors VII and X--different
      genetic mechanisms.
AB  - Combined coagulation factor VII (FVII) and factor X (FX) deficiency (combined
      FVII/FX deficiency) belongs to the group of bleeding disorders in which both
      factors show reduced plasma activity. It may arise from coincidental inheritance
      of separate coagulation factor deficiencies or a common cause as large deletions
      comprising both gene loci. The F7 and F10 genes are located on the long arm of
      chromosome 13. Here, we describe 10 cases with combined FVII/FX deficiency
      representing both genetic mechanisms of occurrence. Genetic analyses included
      direct sequencing of the F7 and F10 genes and MLPA (multiplex ligation-dependent
      probe amplification) for detection of heterozygous large deletions. In four
      patients, the combined deficiency was due to a large deletion within the terminal
      end of chromosome 13. In the remaining six cases the deficiency resulted from
      coincidental inheritance of different genetic alterations affecting both genes
      independently. In most cases, the genetic defects were heterozygous, presenting
      with prolonged PT, normal aPTT and mild or no bleeding symptoms. Only in one case
      compound heterozygous mutations were detected in the F10, resulting in prolonged
      aPTT and a more severe bleeding phenotype. To avoid a misdiagnosis of combined
      FVII/FX deficiency, analyses of single factor activities have to be performed in
      all cases with prolonged PT even if aPTT is normal. Genetic analyses are
      substantial for correct prediction of an inheritance pattern and a proper genetic
      counselling. 

PMID- 25582405
TI  - Environmental, economic and social impact of aviation biofuel production in
      Brazil.
AB  - The Brazilian aviation industry is currently developing biofuel technologies that
      can maintain the operational and energy demands of the sector, while reducing the
      dependence on fossil fuels (mainly kerosene) and greenhouse gas emissions. The
      aim of the current research was to identify the major environmental, economic and
      social impacts arising from the production of aviation biofuels in Brazil.
      Despite the great potential of these fuels, there is a significant need for
      improved routes of production and specifically for lower production costs of
      these materials. In addition, the productive chains of raw materials for
      obtaining these bioenergetics can be linked to environmental impacts by NOx
      emissions, extensive use of agricultural land, loss of wildlife and intensive
      water use, as well as economic, social and political impacts. 

PMID- 25582406
TI  - The neural bases of taxonomic and thematic conceptual relations: an MEG study.
AB  - Converging evidence from behavioral and neuroimaging studies of human concepts
      indicate distinct neural systems for taxonomic and thematic knowledge. A recent
      study of naming in aphasia found involvement of the anterior temporal lobe (ATL)
      during taxonomic (feature-based) processing, and involvement of the
      temporoparietal junction (TPJ) during thematic (function-based) processing. We
      conducted an online magnetoencephalography (MEG) study to examine the spatio
      temporal nature of taxonomic and thematic relations. We measured participants'
      brain responses to words preceded by either a taxonomically or thematically
      related item (e.g., cottage->castle, king->castle). In a separate experiment we
      collected relatedness ratings of the word pairs from participants. We examined
      effects of relatedness and relation type on activation in ATL and TPJ regions of
      interest (ROIs) using permutation t-tests to identify differences in ROI
      activation between conditions as well as single-trial correlational analyses to
      examine the millisecond-by-millisecond influence of the stimulus variables on the
      ROIs. Taxonomic relations strongly predicted ATL activation, and both kinds of
      relations influenced the TPJ. Our results further strengthen the view of the
      ATL's importance to taxonomic knowledge. Moreover, they provide a nuanced view of
      thematic relations as involving taxonomic knowledge.

PMID- 25582407
TI  - Neural correlates of outcome processing post dishonest choice: an fMRI and ERP
      study.
AB  - A dishonest person often utilizes another person's obliviousness to appropriate
      the property that belongs to the other person. Previous researchers have studied
      the making of a dishonest choice and the manipulation of truthful information.
      Here, we have investigated the neural correlates of processing the outcomes of
      dishonest decisions. Participants in this study were asked to interact with
      counterparts in an economic game. They could accept the counterparts' proposals
      on how to divide the profits (honest choice) or choose the alternative plan that
      was advantageous to themselves (dishonest choice), playing to the ignorance of
      their counterparts who had a 50% chance of detecting the situation. Successful
      dishonest choices (not being detected) would bring large rewards, whereas honest
      choices would lead to less of a reward, and failed dishonest choices (being
      caught) would result in no reward. Participants' neural responses during the
      outcome presentations were recorded by functional magnetic resonance imaging
      (fMRI) and event-related potential (ERP) methods in different sessions. We found
      that the outcomes of successful dishonest (vs. honest) choices elicited stronger
      activations in the ventral striatum and posterior cingulate cortex and a smaller
      ERP component called feedback-related negativity (FRN), which suggests that
      positive outcome evaluation and attention processing were aroused by successful
      dishonest choices. Moreover, the outcomes of failed dishonest (relative to
      honest) choices were associated with different neural response patterns in the
      medial orbitofrontal cortex and P3b ERP component between human and computer
      counterparts, suggesting that processing the output of social decision making
      (playing human) is different from that of risk taking (playing computer). The
      findings advanced our understanding about the neural processing of outcome
      presentation after a dishonest choice has been made.

PMID- 25582408
TI  - Impairments in negative emotion recognition and empathy for pain in Huntington's
      disease families.
AB  - Lack of empathy and emotional disturbances are prominent clinical features of
      Huntington's disease (HD). While emotion recognition impairments in HD patients
      are well established, there are no experimental designs assessing empathy in this
      population. The present study seeks to cover such a gap in the literature.
      Eighteen manifest HD patients, 19 first-degree asymptomatic relatives, and 36
      healthy control participants completed two emotion-recognition tasks with
      different levels of contextual dependence. They were also evaluated with an
      empathy-for-pain task tapping the perception of intentional and accidental harm.
      Moreover, we explored potential associations among empathy, emotion recognition,
      and other relevant factors - e.g., executive functions (EF). The results showed
      that both HD patients and asymptomatic relatives are impaired in the recognition
      of negative emotions from isolated faces. However, their performance in emotion
      recognition was normal in the presence of contextual cues. HD patients also
      showed subtle empathy impairments. There were no significant correlations between
      EF, empathy, and emotion recognition measures in either HD patients or relatives.
      In controls, EF was positively correlated with emotion recognition. Furthermore,
      emotion recognition was positively correlated with the performance in the empathy
      task. Our findings highlight the preserved cognitive abilities in HD families
      when using more ecological tasks displaying emotional expressions in the context
      in which they typically appear. Moreover, our results suggest that emotion
      recognition impairments may constitute a potential biomarker of HD onset and
      progression. These results contribute to the understanding of emotion recognition
      and empathy deficits observed in HD and have important theoretical and clinical
      implications. 

PMID- 25582410
TI  - Differentiating malnutrition screening and assessment: a nutrition care process
      perspective.

PMID- 25582409
TI  - 'I was raped by Santa Claus': responding to disclosures of sexual assault in
      mental health inpatient facilities.
AB  - Sexual violence is significantly higher among those with mental illness than the
      rest of the population. The risk of sexual violence posed to patients during
      inpatient admissions is now also beginning to be recognized, but remains a
      challenging area of practice. This paper introduces a trauma-informed care
      approach for responding to disclosures of sexual violence by people with serious
      mental illness, taking into account the complexities of caring for individuals
      who might be unable to provide coherent accounts of assaults and/or who might be
      experiencing varying degrees of psychosis. A framework for understanding and
      responding to disclosures of sexual violence that occur in mental health
      facilities is described, recognizing that such disclosures take many forms,
      including plausible and implausible accounts of recent sexual violence, as well
      as disclosures of past abuse triggered by current traumatic experiences.
      Illustrated by case studies, the practice implications for each type of
      disclosure described in the framework are explored in relation to investigation,
      care planning, and prevention. 

PMID- 25582403
TI  - Hyaluronan fragments as mediators of inflammation in allergic pulmonary disease.
AB  - Asthma is frequently caused and/or exacerbated by sensitization to allergens,
      which are ubiquitous in many indoor and outdoor environments. Severe asthma is
      characterized by airway hyperresponsiveness and bronchial constriction in
      response to an inhaled allergen, leading to a disease course that is often very
      difficult to treat with standard asthma therapies. As a result of interactions
      among inflammatory cells, structural cells, and the intercellular matrix of the
      allergic lung, patients with sensitization to allergens may experience a greater
      degree of tissue injury followed by airway wall remodeling and progressive,
      accumulated pulmonary dysfunction as part of the disease sequela. In addition,
      turnover of extracellular matrix (ECM) components is a hallmark of tissue injury
      and repair. This review focuses on the role of the glycosaminoglycan hyaluronan
      (HA), a component of the ECM, in pulmonary injury and repair with an emphasis on
      allergic asthma. Both the synthesis and degradation of the ECM are critical
      contributors to tissue repair and remodeling. Fragmented HA accumulates during
      tissue injury and functions in ways distinct from the larger native polymer.
      There is gathering evidence that HA degradation products are active participants
      in stimulating the expression of inflammatory genes in a variety of immune cells
      at the injury site. In this review, we will consider recent advances in the
      understanding of the mechanisms that are associated with HA accumulation and
      inflammatory cell recruitment in the asthmatic lung. 

PMID- 25582411
TI  - Xin-deficient mice display myopathy, impaired contractility, attenuated muscle
      repair and altered satellite cell functionality.
AB  - AIM: Xin is an F-actin-binding protein expressed during development of cardiac
      and skeletal muscle. We used Xin-/- mice to determine the impact of Xin
      deficiency on different aspects of skeletal muscle health, including
      functionality and regeneration. METHODS: Xin-/- skeletal muscles and their
      satellite cell (SC) population were investigated for the presence of myopathic
      changes by a series of histological and immunofluorescent stains on resting
      uninjured muscles. To further understand the effect of Xin loss on muscle health
      and its SCs, we studied SCs responses following cardiotoxin-induced muscle
      injury. Functional data were determined using in situ muscle stimulation
      protocol. RESULTS: Compared to age-matched wild-type (WT), Xin-/- muscles
      exhibited generalized myopathy and increased fatigability with a significantly
      decreased force recovery post-fatiguing contractions. Muscle regeneration was
      attenuated in Xin-/- mice. This impaired regeneration prompted an investigation
      into SC content and functionality. Although SC content was not different,
      significantly more activated SCs were present in Xin-/- vs. WT muscles. Primary
      Xin-/- myoblasts displayed significant reductions (approx. 50%) in proliferative
      capacity vs. WT; a finding corroborated by significantly decreased MyoD-positive
      nuclei in 3 days post-injury Xin-/- muscle vs. WT. As more activated SCs did not
      translate to more proliferating myoblasts, we investigated whether Xin-/- SCs
      displayed an exaggerated loss by apoptosis. More apoptotic SCs (TUNEL+/Pax7+)
      were present in Xin-/- muscle vs. WT. Furthermore, more Xin-/- myoblasts were
      expressing nuclear caspase-3 compared to WT at 3 days post-injury. CONCLUSION:
      Xin deficiency leads to a myopathic condition characterized by increased muscle
      fatigability, impaired regeneration and SC dysfunction.

PMID- 25582412
TI  - Effectiveness of dry needling on the lower trapezius in patients with mechanical
      neck pain: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effect of dry needling into a myofascial trigger point
      (MTrP) in the lower trapezius muscle of patients with mechanical idiopathic neck
      pain. DESIGN: A single-center, randomized, double-blinded controlled study.
      SETTING: Patients were recruited from the student population of a local hospital
      by advertisement in the university clinic from January 2010 to December 2011.
      PARTICIPANTS: Patients (N=72) with unilateral neck pain, neck pain for >=3
      months, and active trigger points in the lower trapezius muscle were randomly
      assigned to 1 of 2 treatment groups. All the patients completed the study.
      INTERVENTIONS: Dry needling in an MTrP in the lower trapezius muscle, or dry
      needling in the lower trapezius muscle but not at an MTrP. MAIN OUTCOME MEASURES:
      The visual analog scale (VAS), Neck Pain Questionnaire (NPQ), and pressure-pain
      threshold (PPT) were assessed before the intervention and 1 week and 1 month
      postintervention. RESULTS: Treatment with dry needling of the lower trapezius
      muscle close to the MTrP showed decreases in pain and PPT as well as an
      improvement in the degree of disability (P<.001) compared with the baseline and
      control group measurements (P<.001). The dry-needling technique performed in the
      MTrP showed more significant therapeutic effects (P<.001). CONCLUSIONS: The
      application of dry needling into an active MTrP of the lower trapezius muscle
      induces significant changes in the VAS, NPQ, and PPT levels compared with the
      application of dry needling in other locations of the same muscle in patients
      with mechanical neck pain.

PMID- 25582413
TI  - Well-defined and high resolution Pt nanowire arrays for a high performance
      hydrogen sensor by a surface scattering phenomenon.
AB  - Developing hydrogen (H2) sensors with a high sensitivity, rapid response, long
      term stability, and high throughput is one of the critical issues in energy and
      environmental technology [Hubert et al. Sens. Actuators, B 2011, 157, 329]. To
      date, H2 sensors have been mainly developed using palladium (Pd) as the channel
      material because of its high selectivity and strong affinity to the H2 molecule
      [(Xu et al. Appl. Phys. Lett. 2005, 86, 203104), (Offermans et al. Appl. Phys.
      Lett. 2009, 94, 223110), (Yang et al. Nano Lett. 2009, 9, 2177), (Yang et al. ACS
      Nano 2010, 4, 5233), and (Zou et al. Chem. Commun. 2012, 48, 1033)]. Despite
      significant progress in this area, Pd based H2 sensors suffer from fractures on
      their structure due to hydrogen adsorption induced volumetric swelling during the
      alpha -> beta phase transition, leading to poor long-term stability and
      reliability [(Favier et al. Science 2001, 293, 2227), (Walter et al.
      Microelectron. Eng. 2002, 61-62, 555), and (Walter et al. Anal. Chem. 2002, 74,
      1546)]. In this study, we developed a platinum (Pt) nanostructure based H2 sensor
      that avoids the stability limitations of Pd based sensors. This sensor exhibited
      an excellent sensing performance, low limit of detection (LOD, 1 ppm),
      reproducibility, and good recovery behavior at room temperature. This Pt based H2
      sensor relies on a highly periodic, small cross sectional dimension (10-40 nm)
      and a well-defined configuration of Pt nanowire arrays over a large area. The
      resistance of the Pt nanowire arrays significantly decreased upon exposure to H2
      due to reduced electron scattering in the cross section of the hydrogen adsorbed
      Pt nanowires, as compared to the oxygen terminated original state. Therefore,
      these well-defined Pt nanowire arrays prepared using advanced lithographic
      techniques can facilitate the production of high performance H2 sensors.

PMID- 25582414
TI  - Biochemical Characterization of a Novel Endo-1,5-alpha-l-arabinanase from
      Rhizomucor miehei.
AB  - A novel gene (designated as RmArase) encoding endo-1,5-alpha-l-arabinanase from a
      thermophilic fungus Rhizomucor miehei was cloned and expressed in Escherichia
      coli. The gene had an open reading frame (ORF) of 930 base pairs (bp) encoding
      309 amino acids. The amino acid sequence shared highest identity (56%) with a
      glycoside hydrolase (GH) family 43 endo-1,5-alpha-l-arabinase from Bacillus
      subtilis and low identity (35%) with the endo-1,5-alpha-l-arabinase from
      Aspergillus niger. The recombinant endo-1,5-alpha-l-arabinase (RmArase) was
      purified to homogeneity with a molecular mass of 40.6 kDa. The purified enzyme
      had a specific activity of 109 units/mg. The optimal temperature and pH of
      RmArase were determined to be 55  degrees C and 5.5, respectively. It was stable
      up to 45  degrees C and within pH 5.0-8.5. The Km values of RmArase toward
      debranched arabinan and sugar beet arabinan were 5.8 and 27.5 mg/mL,
      respectively. RmArase efficiently degraded arabinans to yield and arabinobiose
      and arabinose as major end products, which was different from most other endo-1,5
      alpha-l-arabinases. The synergistic action of RmArase and the pectinase could
      significantly improve the degradation of sugar beet pulp. These properties make
      RmArase useful in several industries.

PMID- 25582415
TI  - Compound Danshen (Salvia miltiorrhiza) dripping pill for coronary heart disease:
      an overview of systematic reviews.
AB  - Compound Danshen dripping pill (CDDP) is commonly used to treat coronary heart
      disease (CHD) in China. However, clinical practice has not been informed by
      evidence from relevant systematic reviews (SRs). This overview aims at
      summarizing evidence from SRs on CDDP for the treatment of CHD. We included SRs
      of randomized controlled trials (RCTs) on CDDP in treating CHD until March 2014
      by searching the Cochrane Library, PubMed, EMBASE and four Chinese databases.
      Data were extracted according to a pre-designed form. We assessed the quality of
      SRs according to AMSTAR and graded the quality of evidence in the included SRs
      using the GRADE approach. All data analyses were descriptive. About 13 SRs
      involving a total of 34,071 participants with angina or acute myocardial
      infarction (AMI) were included. Few SRs assessed endpoints (5/13, 38.5%) and
      quality of life (QOL) (4/13, 30.8%). Most of the SRs suggested that CDDP had
      potential benefits for patients with CHD, such as improving symptoms and
      electrocardiogram (ECG) results, with few adverse reactions, while benefits in
      endpoints were unproved. Moreover, the overall quality of evidence in the SRs was
      poor, ranging from "very low" to "moderate", and most of the included SRs were of
      "low" (3/13, 23.1%) or "moderate" (9/13, 69.2%) quality with many serious flaws.
      Current SRs suggested potential benefits of CDDP for the treatment of CHD.
      However, high-quality evidence is warranted to support the application of CDDP in
      treating CHD. 

PMID- 25582416
TI  - Are common measures of dietary restraint and disinhibited eating reliable and
      valid in obese persons?
AB  - Disordered eating measures were developed and validated in primarily normal
      weight samples; thus, it is unclear if the psychometric properties are equivalent
      across weight groups. This study evaluated the reliability and validity of self
      reported disinhibited eating and dietary restraint measures in a community
      recruited sample of overweight individuals (N = 201) and obese individuals (N =
      101) and normal weight matched controls. Coefficient alpha and average inter-item
      correlations were used to test internal consistency reliability. Correlations
      between lifetime disordered eating behaviors and measures of dietary restraint
      and disinhibited eating were used to test convergent validity. Disordered eating
      measures included: Eating Disorders Examination Questionnaire (EDE-Q), Three
      Factor Eating Questionnaire (TFEQ), Dutch Eating Behavior Questionnaire (DEBQ),
      Eating Disorders Inventory-3 (EDI-3), and Restraint Scale. Correlations between
      lifetime disordered eating behaviors and measures of non-disordered-eating
      related psychopathology were used to test discriminant validity. Results
      indicated that most measures demonstrated acceptable internal consistency
      reliability across groups, with the exception of the Restraint Scale.
      Significantly higher convergent correlations between lifetime history of fasting
      and TFEQ Cognitive Restraint emerged for the overweight vs. obese group, and the
      magnitude of discriminant correlations between lifetime history of binge eating
      and the Inventory of Depression and Anxiety Symptoms (IDAS) Well Being scale was
      stronger in the normal weight vs. overweight group. Findings suggest the majority
      restrained and disinhibited eating measures are reliable and valid among weight
      groups, and are suitable to use in overweight and obese populations. 

PMID- 25582417
TI  - Facets of impulsivity interactively predict body fat and binge eating in young
      women.
AB  - Impulsivity has been positively linked to overeating and obesity, but findings
      are inconsistent. Studies using the Barratt Impulsiveness Scale (BIS) show that
      measures of overeating appear to be most consistently associated with scores on
      the subscale attentional impulsivity in both non-clinical and clinical samples.
      Additionally, individuals with binge-eating behaviors may have elevated scores on
      the subscale motor impulsivity. In the current study, young women (N = 133)
      completed the short form of the BIS (BIS-15), the Eating Disorder Examination -
      Questionnaire, and height, weight and body composition were measured. Regression
      analyses showed that attentional and motor impulsivity positively predicted binge
      eating and general eating pathology, while non-planning impulsivity negatively
      predicted these variables. Moreover, attentional and motor impulsivity
      interactively predicted percent body fat, and the number of subjective and
      objective binge episodes. Results show that only specific aspects of trait
      impulsivity (attentional and motor impulsivity) are positively associated with
      body mass and binge eating. Non-planning impulsivity appears to be unrelated or
      even inversely related to those variables, at least in female students. Elevated
      levels of attentional impulsivity in conjunction with high motor impulsivity may
      be a risk factor for overweight and clinically relevant binge eating. 

PMID- 25582418
TI  - Paediatric ECMO at low-volume paediatric cardiac centres in the Nordic countries.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving resource
      intensive technology for patients with respiratory and/or circulatory failure. We
      aimed to evaluate outcome data from three Nordic paediatric centres comparing
      with data from the International Registry of the Extracorporeal Life Support
      Organization (ELSO) and selected high-volume single-centre studies. METHODS: One
      hundred nineteen patients < 19 years from 2002 to 2012 were enrolled. Data on
      demographics and outcome were collected using a standardised registration form.
      Outcome data were compared with the ELSO registry and high-volume single-centre
      studies. RESULTS: Demographics, indications and diagnosis were similar to the
      ELSO register. Survival after ECMO was similar to outcome data from the ELSO
      register, apart from paediatric cardiac ECMO, where a significantly better
      survival to discharge was seen in the Nordic centres (68% vs. 49%; P = 0.03).
      Comparison with high-volume centres in the period after 2005 demonstrated a
      significantly better survival after cardiac ECMO in a single high-volume centre
      study, whereas four studies had significantly lower survival after cardiac ECMO.
      No significant difference was seen in children receiving respiratory ECMO in the
      Nordic centres and high-volume centres. CONCLUSIONS: Survival after ECMO in three
      low-volume Nordic centres demonstrated comparable outcome data with ELSO data and
      data from high-volume centres. We believe regular quality assurance surveys, as
      the present study, should be performed in order to maintain excellent therapy
      within the individual ECMO centres.

PMID- 25582420
TI  - Vasorelaxing effects of the soluble guanylyl cyclase activator BAY 60-2770 in
      nitrate-tolerant monkey and canine coronary arteries.
AB  - Nitrate tolerance is an important problem in the treatment of ischemic heart
      diseases. The present study investigated whether or not a soluble guanylyl
      cyclase (sGC) activator can be used as a coronary vasodilator under nitrate
      tolerant conditions. Helically cut strips of endothelium-denuded monkey and
      canine coronary arteries were suspended in organ chambers for isometric tension
      recording. Nitrate tolerance was induced by a 1-h treatment with nitroglycerin
      (0.1 mM) followed by 1-h washout of the agent. Control strips were not exposed
      previously to nitroglycerin, but otherwise were treated identically. The relaxant
      response to nitroglycerin was dramatically impaired by previous exposure to the
      drug for 1 h in either monkey or canine coronary arteries, indicating the
      development of nitrate tolerance. In contrast, development of nitrate tolerance
      did not affect the relaxant potency and efficacy of the sGC activator BAY 60-2770
      in either the monkey or canine coronary arteries. These findings suggest that it
      may be possible to use sGC activators as substitute drugs for nitroglycerin if
      tolerance is developed during the treatment of ischemic heart diseases. 

PMID- 25582421
TI  - The Diagnostic Value of Transvaginal Sonograph (TVS), Color Doppler, and Serum
      Tumor Marker CA125, CEA, and AFP in Ovarian Cancer.
AB  - The purpose of this study is to investigate the diagnostic value of transvaginal
      sonograph (TVS), color Doppler, and serum tumor marker CA125, CEA, and AFP in
      ovarian cancer. From June, 2011 to May, 2013, 102 cases with adnexal mass were
      recruited in this study (32 cases of malignant ovarian cancer and 70 cases of
      benign ovarian tumor according to pathological diagnosis). TVS, color Doppler,
      and serum tumor markers were used for tumor diagnosis. The sensitivity,
      specifity, positive prediction, negative prediction, and Youden's index were
      analyzed. Of the 102 patients, 32 were diagnosed with malignant ovarian cancer
      and 70 were diagnosed with benign ovarian tumor according to pathological
      diagnosis. Based on TVS results, 37 cases were malignant while 65 cases were
      benign. Based on color Doppler results, 34 cases were malignant while 68 cases
      were benign. Based on TVS and color Doppler results, 35 cases were malignant
      while 65 were benign. Based on CA125 test results, 34 cases were malignant while
      68 cases were benign. Based on CEA test results, 8 cases were malignant and 94
      cases were benign. Bases on AFP test results, 9 cases were malignant while 93
      cases were benign. Based on the results of combination tumor marker test, 38
      cases were malignant while 64 cases were benign. The combination of TVS, color
      Doppler, and tumor marker test showed optimal diagnostic value with a sensitivity
      of 90.63 %, specificity of 97.14 %, positive prediction of 93.94 %, negative
      prediction of 98.55 %, and Youden's index of 94.02 %. The combination of TVS,
      color Doppler, and tumor marker test is of great diagnostic value, which should
      be widely used in clinical practice. 

PMID- 25582419
TI  - A highly regio- and stereoselective synthesis of alpha-fluorinated imides via
      fluorination of chiral enamides.
AB  - A highly pi-facial selective and regioselective fluorination of chiral enamides
      is described. The reaction involves an enantioselective fluorination exclusively
      at the electron-rich enamide olefin with N-F reagents such as Selectfluor and N
      fluoro-benzenesulfonimide [NFSI] accompanied by trapping of the beta-fluoro
      iminium cationic intermediate with water. The resulting N,O-hemiacetal could be
      oxidized using Dess-Martin periodinane, leading to an asymmetric sequence for
      syntheses of chiral alpha-fluoro-imides and optically enriched alpha-fluoro
      ketones. 

PMID- 25582422
TI  - Research to Improve the Efficiency of Double Stereo PCR Microfluidic Chip by
      Passivating the Inner Surface of Steel Capillary with NOA61.
AB  - In this paper, we report the improvement of PCR microfluidic chip efficiency
      achieved by coating the inner surface of steel capillary microchannel with a 22
      um film of the ultraviolet-solidified NOA61 using a device invented by us. Our
      results indicate that with this treatment, the roughness of the inside wall of
      steel capillary was improved from Ra = 0.921 to Ra = 0.254. The contact angle was
      decreased from about 95 degrees  to 56 degrees , and the surface hydrophobicity
      was also increased. The flow pressure for performing the real-time PCR in the
      microfluidic chip with modified surface was reduced by twofold (2.11/1) and that
      resulted in a substantially increased efficiency of PCR. A modification of the
      microchannel interior surface improved the quality of the on-chip integrated PCR
      procedure. 

PMID- 25582423
TI  - Whey protein isolate decreases murine stomach weight and intestinal length and
      alters the expression of Wnt signalling-associated genes.
AB  - The present study examined the underlying mechanisms by which whey protein
      isolate (WPI) affects energy balance. C57BL/6J mice were fed a diet containing
      10% energy from fat, 70% energy from carbohydrate (35% energy from sucrose) and
      20% energy from casein or WPI for 15 weeks. Mice fed with WPI had reduced weight
      gain, cumulative energy intake and dark-phase VO2 compared with casein-fed mice
      (P< 0.05); however, WPI intake had no significant effects on body composition,
      meal size/number, water intake or RER. Plasma levels of insulin, TAG, leptin,
      glucose and glucagon-like peptide 1 remained unchanged. Notably, the intake of
      WPI reduced stomach weight and both length and weight of the small intestine (P<
      0.05). WPI intake reduced the gastric expression of Wingless/int-1 5a (Wnt5a) (P<
      0.01) and frizzled 4 (Fzd4) (P< 0.01), with no change in the expression of
      receptor tyrosine kinase-like orphan receptor 2 (Ror2) and LDL receptor-related
      protein 5 (Lrp5). In the ileum, WPI increased the mRNA expression of Wnt5a (P<
      0.01) and caused a trend towards an increase in the expression of Fzd4 (P=
      0.094), with no change in the expression of Ror2 and Lrp5. These genes were
      unresponsive in the duodenum. Among the nutrient-responsive genes, WPI
      specifically reduced ileal mRNA expression of peptide YY (P< 0.01) and fatty acid
      transporter protein 4 (P< 0.05), and decreased duodenal mRNA expression of the
      insulin receptor (P= 0.05), with a trend towards a decreased expression of Na
      glucose co-transporter 1 (P= 0.07). The effects of WPI on gastrointestinal Wnt
      signalling may explain how this protein affects gastrointestinal structure and
      function and, in turn, energy intake and balance.

PMID- 25582424
TI  - Diastolic dysfunction in the diabetic continuum: association with insulin
      resistance, metabolic syndrome and type 2 diabetes.
AB  - BACKGROUND: Diabetes increases the risk of heart failure but the underlying
      mechanisms leading to diabetic cardiomyopathy are poorly understood. Left
      ventricle diastolic dysfunction (LVDD) is one of the earliest cardiac changes in
      these patients. We aimed to evaluate the association between LVDD with insulin
      resistance, metabolic syndrome (MS) and diabetes, across the diabetic continuum.
      METHODS: Within a population-based study (EPIPorto), a total of 1063 individuals
      aged >=45 years (38% male, 61.2 +/- 9.6 years) were evaluated. Diastolic function
      was assessed by echocardiography, using tissue Doppler analysis (E' velocity and
      E/E' ratio) according to the latest consensus guidelines. Insulin resistance was
      assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
      score. RESULTS: The HOMA-IR score correlated to E' velocity (rho = -0.20;p <
      0.0001) and E/E' ratio (rho = 0.20; p < 0.0001). There was a progressive
      worsening in E' velocity (p for trend < 0.001) and in E/E' ratio across HOMA-IR
      quartiles (p for trend <0.001). Individuals in the highest HOMA-IR quartile were
      more likely to have LVDD, even after adjustment for age, sex, blood pressure and
      body mass index (adjusted OR: 1.82; 95% CI: 1.09-3.03). From individuals with no
      MS, to patients with MS and no diabetes, to patients with diabetes, there was a
      progressive decrease in E' velocity (11.2 +/- 3.3 vs 9.7 +/- 3.1 vs 9.2 +/- 2.8
      cm/s; p < 0.0001), higher E/E' (6.9 +/- 2.3 vs 7.8 +/- 2.7 vs 9.0 +/- 3.6; p <
      0.0001) and more diastolic dysfunction (adjusted OR: 1.62; 95% CI: 1.12-2.36 and
      1.78; 95% CI: 1.09-2.91, respectively). CONCLUSIONS: HOMA-IR score and metabolic
      syndrome were independently associated with LVDD. Changes in diastolic function
      are already present before the onset of diabetes, being mainly associated with
      the state of insulin resistance.

PMID- 25582426
TI  - Application of supercritical water to decompose brominated epoxy resin and
      environmental friendly recovery of metals from waste memory module.
AB  - Waste Memory Modules (WMMs), a particular kind of waste printed circuit board
      (WPCB), contain a high amount of brominated epoxy resin (BER), which may bring a
      series of environmental and health problems. On the other hand, metals like gold
      and copper are very valuable and are important to recover from WMMs. In the
      present study, an effective and environmental friendly method using supercritical
      water (SCW) to decompose BER and recover metals from WMMs was developed instead
      of hydrometallurgy or pyrometallurgy simultaneously. Experiments were conducted
      under external-catalyst-free conditions with temperatures ranging from 350 to 550
      degrees C, pressures from 25 to 40 MPa, and reaction times from 120 to 360 min
      in a semibatch-type reactor. The results showed that BER could be quickly and
      efficiently decomposed under SCW condition, and the mechanism was possibly free
      radical reaction. After the SCW treatments, the glass fibers and metal foils in
      the solid residue could be easily liberated and recovered, respectively. The
      metal recovery rate reached 99.80%. The optimal parameters were determined as 495
      degrees C, 33 MPa, and 305 min on the basis of response surface methodology
      (RSM). This study provides an efficient and environmental friendly approach for
      WMMs recycling compared with electrolysis, pyrometallurgy, and hydrometallurgy. 

PMID- 25582425
TI  - Treatment outcomes of extended-field radiation therapy and the effect of
      concurrent chemotherapy on uterine cervical cancer with para-aortic lymph node
      metastasis.
AB  - PURPOSE: To review the clinical outcomes of extended-field radiation therapy
      (EFRT) and to analyze prognostic factors significant for survival in patients
      receiving EFRT for uterine cervical carcinoma with para-aortic node (PAN)
      metastasis. PATIENTS AND METHODS: We retrospectively reviewed 90 patients with
      stage IB-IVA cervical cancer and PAN metastasis between 1987 and 2012. Median age
      was 50 (range, 24-77). Patients received median 70.2 Gy (range, 56-93) to point A
      and median 50.4 Gy (range, 45-60.4) to PAN over median 69 elapsed days (range, 43
      182). Forty-six patients (51.1%) received concurrent chemotherapy. Survival was
      calculated using the Kaplan-Meier method. We analyzed prognostic factors for
      overall actuarial survival (OS) and progression-free survival (PFS) using a Cox
      regression method. RESULTS: The median follow-up period for surviving patients
      was 55 months (range, 3-252). Seventy patients (77.8%) had complete remission.
      Forty-six patients experienced treatment failure as follows: 11 patients (12.2%)
      as local recurrence, 19 (21%) as regional recurrence and 33 (36.7%) as distant
      metastasis. The 5-yr OS and PFS were 62.6% and 43.9%, respectively. Treatment
      response was the only statistically independent prognostic factors for OS (p=
      0.04) and PFS (p< 0.001) on multivariate analysis. Grade 3 or 4 hematologic
      gastrointestinal and urogenital toxicities were observed in about 10% of
      patients. CONCLUSIONS: Our institutional experiences showed that EFRT was an
      effective treatment for cervical cancer patients with PAN metastasis. The
      addition of chemotherapy to EFRT seems to have uncertain survival benefit with
      higher hematologic toxicity.

PMID- 25582428
TI  - Submuscular implantation of insertable cardiac monitors improves the reliability
      of detection of atrial fibrillation.
AB  - PURPOSE: Diagnosing atrial fibrillation (AF) is highly relevant, as specific
      secondary prevention is of high importance. Recently, insertable cardiac monitors
      (ICMs) have been introduced for continuous monitoring to detect asymptomatic
      episodes of AF. The detection of AF remains challenging due to a relevant
      incidence of artifacts. This study aimed to compare the effectivity of ICM when
      placed in a subcutaneous or in a submuscular localization, respectively. METHODS:
      We retrospectively analyzed data from 30 patients undergoing pulmonary vein
      isolation (PVI) for AF and consecutive ICM implantation. ICMs were implanted in
      two locations: either subcutaneously and parasternally (SC) or under the left
      major pectoral muscle (SP). Interrogations were continuously retrieved using
      remote monitoring and during repeated visits in our outpatient clinic. The
      transmission protocols were scanned for detected AF, and it was ruled by two
      blinded investigators, if detection was correct or incorrect. RESULTS: Mean age
      was 67 +/- 10 years, 56% men, 50% paroxysmal AF. In 14 of the patients, the ICM
      was implanted at a SC localization and in 16 patients subpectorally. R-wave
      amplitude was significantly higher in patents with SP implantation. There were
      670 transmitted protocols including 1024 episodes detected as AF. Of these, 54%
      were correctly recognized as AF in the SC group. In the SP group, 85% of the
      recorded episodes were correctly recognized as AF (p = 0.03). The remaining
      episodes in both groups showed sinus rhythm with misinterpreted artifacts.
      CONCLUSIONS: To improve effectiveness of detecting AF episodes, it is useful to
      implant subpectorally.

PMID- 25582427
TI  - Expression of Septin4 in Schistosoma japonicum-infected mouse livers after
      praziquantel treatment.
AB  - BACKGROUND: Septin4 (SEPT4) exists widely in human tissues and is related to
      mechanical stability, actin dynamics, membrane trafficking, viral replication and
      apoptosis. Data from many studies have suggested that SEPT4 plays a significant
      role in liver fibrosis. SEPT4 is down-regulated in the model of CCl4 and BDL
      treated liver fibrosis. However, it is up-regulated and peaked at 12 weeks post
      infection (p.i.), and then decreased subsequently in Schistosoma japonicum (S.
      japonicum) egg-induced liver fibrosis. The aim of this study was to observe the
      dynamic alteration of SEPT4 after the treatment of praziquantel (PZQ) in ICR mice
      infected with S. japonicum. METHODS: Expression of SEPT4 was determined by
      western blot, immunofluorescence and qRT-PCR. And pro-inflammatory cytokines IL-6
      and TNF-alpha were detected by qRT-PCR. The number of eggs, the diameter of egg
      granulomas and fibrosis-associated genes were also measured. RESULTS: Our results
      showed that the granulomatous inflammation was reduced, whereafter the expression
      of SEPT4 on hepatic stellate cells (HSCs) was decreased after PZQ anti
      schistosome therapy. And the variation tendency of SEPT4 had positive correlation
      with the inflammatory response in the area of S. japonicum egg granulomas.
      CONCLUSIONS: Based on these findings, the inhibition of the expression of the
      SEPT4 by PZQ might be due to alleviation of the inflammatory response at the
      chronic and advanced stage of S. japonicum infection.

PMID- 25582429
TI  - Descriptive study of the role of household type and household composition on
      women's reproductive health outcomes in urban Uttar Pradesh, India.
AB  - BACKGROUND: More needs to be known about the role intra-familial power dynamics
      play in women's reproductive health outcomes, particularly in societies like
      Northern India characterized by patriarchy and extended families. The key
      research question we explore is: how important are living arrangements (e.g.,
      presence of the mother-in-law, presence of an elder sister-in-law, and living in
      the husband's natal home) on contraceptive use behaviors and decision to deliver
      at an institution? METHODS: Representative data collected in 2010 from six cities
      in Uttar Pradesh are used to examine the above research question. This study uses
      multivariable logistic regression methods to examine the association between
      women's household type (husband's natal home vs. not husband's natal home) and
      household composition (lives with mother-in-law; and lives with elder sister-in
      law) and modern family planning use and institutional delivery. RESULTS: More
      than sixty percent of women in the sample live in their husband's natal home, one
      third live with their mother-in-law, and only three percent live with an elder
      sister-in-law. Findings demonstrate that women who live either with the mother-in
      law or in the husband's natal home are more likely to use modern family planning
      than those women living neither with the mother-in-law nor in the husband's natal
      home. In addition, living with an elder sister-in-law is associated with less
      family planning use. For institutional delivery, women who live with the mother
      in-law have higher institutional delivery than those not living with the mother
      in-law. Multivariable analyses demonstrate that, controlling for other factors
      associated with modern family planning use, women living with neither the mother
      in-law nor in the husband's natal home are the least likely to use modern family
      planning. Similar findings are found for institutional delivery such that those
      women living with neither the mother-in-law nor in the husband's natal home are
      the least likely to have an institutional delivery, controlling for demographic
      factors associated with institutional delivery. CONCLUSIONS: Where women live and
      who they live with matters. Future reproductive health programs for urban India
      should consider these context specific factors in programs seeking to improve
      women's reproductive health outcomes.

PMID- 25582430
TI  - Audio-visual speech intelligibility benefits with bilateral cochlear implants
      when talker location varies.
AB  - One of the key benefits of using cochlear implants (CIs) in both ears rather than
      just one is improved localization. It is likely that in complex listening scenes,
      improved localization allows bilateral CI users to orient toward talkers to
      improve signal-to-noise ratios and gain access to visual cues, but to date, that
      conjecture has not been tested. To obtain an objective measure of that benefit,
      seven bilateral CI users were assessed for both auditory-only and audio-visual
      speech intelligibility in noise using a novel dynamic spatial audio-visual test
      paradigm. For each trial conducted in spatially distributed noise, first, an
      auditory-only cueing phrase that was spoken by one of four talkers was selected
      and presented from one of four locations. Shortly afterward, a target sentence
      was presented that was either audio-visual or, in another test configuration,
      audio-only and was spoken by the same talker and from the same location as the
      cueing phrase. During the target presentation, visual distractors were added at
      other spatial locations. Results showed that in terms of speech reception
      thresholds (SRTs), the average improvement for bilateral listening over the
      better performing ear alone was 9 dB for the audio-visual mode, and 3 dB for
      audition-alone. Comparison of bilateral performance for audio-visual and audition
      alone showed that inclusion of visual cues led to an average SRT improvement of 5
      dB. For unilateral device use, no such benefit arose, presumably due to the
      greatly reduced ability to localize the target talker to acquire visual
      information. The bilateral CI speech intelligibility advantage over the better
      ear in the present study is much larger than that previously reported for static
      talker locations and indicates greater everyday speech benefits and improved cost
      benefit than estimated to date. 

PMID- 25582431
TI  - Infection with Helicobacter bilis but not Helicobacter hepaticus was Associated
      with Extrahepatic Cholangiocarcinoma.
AB  - BACKGROUND AND AIMS: The biliary tract cancer or cholangiocarcinoma (CCA)
      represents the sixth leading cause of gastrointestinal tumors in the Western
      world, and mortality varies across the world, with regions such as Chile,
      Thailand, Japan, and northeastern India presenting the highest rates. CCA may
      develop in the bile duct, gallbladder, or ampulla of Vater; and risk factors
      include obesity, parity, genetic background, geographical and environmental
      factors. Inflammation induced by bacterial infections might play a role in the
      pathogenesis of CCA. In this work, we investigated whether there is an
      association between extrahepatic cholangiocarcinoma (ECCA) and infection with S.
      typhi, H. hepaticus, or H. bilis in a Mexican population. METHODS: A total of 194
      patients were included and divided into 91 patients with benign biliary pathology
      (controls) and 103 with ECCA (cases). Tumor samples were taken during endoscopic
      retrograde cholangiopancreatography by biliary brushing, followed by DNA
      extraction and PCR testing for infections. RESULTS: We found that 44/103 cases
      were positive for H. bilis, compared with 19/91 controls (p = 0.002; OR 2.83, 95%
      CI 1.49-5.32), and when analyzed by sub-site, H. bilis infection was
      significantly more associated with cancer in the common bile duct (p = 0.0005; OR
      3.56, 95% CI 1.77-7.17). In contrast, H. hepaticus infection was not different
      between cases (17/103) and controls (13/91) (p = 0.82; OR 1.19, 95% CI 0.54
      2.60). None of the samples were positive for S. typhi infection. CONCLUSION: In
      conclusion, infection with H. bilis but neither H. Hepaticus nor S. typhi was
      significantly associated with ECCA, particularly with tumors located in the
      common bile duct.

PMID- 25582432
TI  - Establishment of indirect enzyme-linked immunosorbent assay for artificial musk.
AB  - Anti-inflammatory component (AIC) known as an important constituent of artificial
      musk exhibits bioactive effects on many pharmacological models. This study
      describes an immunochemical assay for the quality control of artificial musk in
      traditional Chinese medicine using an enzyme-linked immunosorbent assay. A
      polyclonal antibody against AIC was produced by rabbit. The method, at an
      effective measuring range of 3.13-200 ng/ml of AIC, 3 ng/ml limit of detection,
      and no cross-reaction with natural musk, successfully detected artificial musk in
      many traditional Chinese prescriptions containing artificial musk. The results
      demonstrated that a novel and reliable assay system for detection of artificial
      musk was generated. 

PMID- 25582434
TI  - Effect of lower limb compression on blood flow and performance in elite
      wheelchair rugby athletes.
AB  - OBJECTIVE: To investigate the effects of compression socks worn during exercise
      on performance and physiological responses in elite wheelchair rugby athletes.
      DESIGN: In a non-blinded randomized crossover design, participants completed two
      exercise trials (4 * 8 min bouts of submaximal exercise, each finishing with a
      timed maximal sprint) separated by 24 hr, with or without compression socks.
      SETTING: National Sports Training Centre, Queensland, Australia. PARTICIPANTS:
      Ten national representative male wheelchair rugby athletes with cervical spinal
      cord injuries volunteered to participate. INTERVENTIONS: Participants wore
      medical grade compression socks on both legs during the exercise task (COMP), and
      during the control trial no compression was worn (CON). OUTCOME MEASURES: The
      efficacy of the compression socks was determined by assessments of limb blood
      flow, core body temperature, heart rate, and ratings of perceived exertion,
      perceived thermal strain, and physical performance. RESULTS: While no significant
      differences between conditions were observed for maximal sprint time, average lap
      time was better maintained in COMP compared to CON (P<0.05). Lower limb blood
      flow increased from pre- to post-exercise by the same magnitude in both
      conditions (COMP: 2.51 +/- 2.34; CON: 2.20 +/- 1.85 ml.100 ml.(-1)min(-1)),
      whereas there was a greater increase in upper limb blood flow pre- to post
      exercise in COMP (10.77 +/- 8.24 ml.100 ml.(-1)min(-1)) compared to CON (6.21 +/-
      5.73 ml.100 ml.(-1)min(-1); P < 0.05). CONCLUSION: These findings indicate that
      compression socks worn during exercise is an effective intervention for
      maintaining submaximal performance during wheelchair exercise, and this
      performance benefit may be associated with an augmentation of upper limb blood
      flow.

PMID- 25582436
TI  - Eye tracking detects disconjugate eye movements associated with structural
      traumatic brain injury and concussion.
AB  - Disconjugate eye movements have been associated with traumatic brain injury since
      ancient times. Ocular motility dysfunction may be present in up to 90% of
      patients with concussion or blast injury. We developed an algorithm for eye
      tracking in which the Cartesian coordinates of the right and left pupils are
      tracked over 200 sec and compared to each other as a subject watches a short film
      clip moving inside an aperture on a computer screen. We prospectively eye tracked
      64 normal healthy noninjured control subjects and compared findings to 75 trauma
      subjects with either a positive head computed tomography (CT) scan (n=13),
      negative head CT (n=39), or nonhead injury (n=23) to determine whether eye
      tracking would reveal the disconjugate gaze associated with both structural brain
      injury and concussion. Tracking metrics were then correlated to the clinical
      concussion measure Sport Concussion Assessment Tool 3 (SCAT3) in trauma patients.
      Five out of five measures of horizontal disconjugacy were increased in positive
      and negative head CT patients relative to noninjured control subjects. Only one
      of five vertical disconjugacy measures was significantly increased in brain
      injured patients relative to controls. Linear regression analysis of all 75
      trauma patients demonstrated that three metrics for horizontal disconjugacy
      negatively correlated with SCAT3 symptom severity score and positively correlated
      with total Standardized Assessment of Concussion score. Abnormal eye-tracking
      metrics improved over time toward baseline in brain-injured subjects observed in
      follow-up. Eye tracking may help quantify the severity of ocular motility
      disruption associated with concussion and structural brain injury. 

PMID- 25582437
TI  - Correlation between CT perfusion and clinico-pathological features in prostate
      cancer: a prospective study.
AB  - BACKGROUND: The aim of the study was to assess the correlation between computed
      tomography perfusion (PCT) parameters and PSA levels, Gleason score, and pTNM
      stage in patients with prostate cancer (PCa). MATERIAL/METHODS: One hundred
      twenty-five patients with localized PCa were prospectively enrolled in the study.
      All patients were diagnosed due to suspicious prostate findings and elevated PSA
      serum levels and underwent PCT followed by core biopsy and radical prostatectomy.
      Blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability
      surface (PS) area product were computed in the suspected PCa area and normal
      prostatic tissue. Core biopsy followed by prostatectomy was performed 2-4 weeks
      after PCT. Correlation between PCT findings and PSA levels, Gleason score, and
      pTNM stage were analyzed. RESULTS: The mean age of patients was 64 years. All
      patients had elevated PSA levels (mean value 6.2 ng/ml). Nineteen patients
      (15.9%) were at low risk of recurrence, 91 (76.5%) were at moderate risk, and 9
      (7.6%) were at high risk according to National Comprehensive Cancer Network
      criteria. PCa was visible on PCT as focal peripheral CT enhancement in 119 out of
      125 patients (sensitivity 95.2%). Significant correlations between BV, BF, and PS
      values and PSA level were found (p<0.05), as well as a trend for difference
      between BV, BF, and PS in poorly and moderately differentiated tumors (according
      to Gleason score) in comparison with highly differentiated PCa (p<0.08). The
      analysis also revealed a correlation between mean perfusion values and BV, MTT,
      PS, and pTNM cancer stage (p<0.04). CONCLUSIONS: Our study suggests that in low-
      and intermediate- risk patients, PCT parameters correlate with PSA values,
      Gleason score, and pTNM stage and can be useful for initial tumor staging.

PMID- 25582439
TI  - Distal embolization of hydrophilic-coating material from coronary guidewires
      after percutaneous coronary interventions.
AB  - BACKGROUND: Coronary guidewires are indispensable during percutaneous coronary
      interventions. Nowadays, most guidewires have hydrophilic coatings to improve
      their trackability, allowing easy lesion passage and facilitating balloon and
      stent positioning. Recent reports, however, have raised concerns about detachment
      and subsequent embolization of these hydrophilic coatings. METHODS AND RESULTS:
      We have retrospectively reviewed the histological samples of the myocardium,
      obtained during autopsies in the period 2009 to 2013, from all patients who had a
      history of percutaneous coronary interventions (n=40). Foreign material was
      observed in the distal myocardium in 4 patients (10%). Furthermore, we have
      reviewed 205 thrombus specimens which were obtained during thrombus aspiration in
      the setting of primary percutaneous coronary interventions in the period 2005 to
      2009. In 45% of the cases, foreign material was observed within the thrombus.
      Finally, we have examined the histopathologic appearance of hydrophilic-guidewire
      coating material ex vivo by embedding the coating in placenta specimen and cut
      and stain it in exactly the same manner as the myocardium and thrombus specimen.
      The histopathologic appearance of the hydrophilic coating ex vivo was identical
      to the foreign material found in vivo. CONCLUSIONS: Distal embolization of
      hydrophilic-coating material was observed in 10% of the patients who had a
      history of percutaneous coronary interventions. Hydrophilic-coating material was
      found in 45% of coronary thrombus specimen obtained during thrombus aspiration.
      These findings suggest that detachment and distal embolization of hydrophilic
      coating material from coronary guidewires occur more often than the sparse
      literature on this topic suggests.

PMID- 25582438
TI  - RAGE gene polymorphism and environmental factor in the risk of oral cancer.
AB  - Oral squamous cell carcinoma is a common neoplasm that is known to be causally
      associated with genetic factors and environmental carcinogens. The receptor for
      advanced glycosylation endproducts (RAGE) is a transmembrane protein of the
      immunoglobulin superfamily with broad specificity for multiple ligands, and it
      has been shown to play vital roles in several pathophysiologic processes,
      including diabetes, Alzheimer disease, renal disease, cardiovascular disease, and
      cancer. The present study aimed to assess the influences of RAGE gene
      polymorphisms, combined with environmental carcinogens on the predisposition to
      oral tumorigenesis. Five polymorphisms of the RAGE gene-including -374T>A
      (rs1800624), -429T>C (rs1800625), 1704G>T (rs184003), Gly82Ser (rs2070600), and a
      63-bp deletion allele (-407 to -345)-were examined from 592 controls and 618
      patients with oral cancer. We found that individuals carrying the polymorphic
      allele of rs1800625 are more susceptible to oral cancer (odds ratio [OR], 1.899;
      95% confidence interval [CI], 1.355 to 2.661; adjusted OR [AOR], 2.053; 95% CI,
      1.269 to 3.345) after adjustment for age, sex, betel nut chewing, and tobacco
      consumption. Moreover, we observed a significant association of rs1800625
      variants with late-stage tumors (stage III/IV, OR, 1.736; 95% CI, 1.126 to 2.677;
      AOR, 1.771; 95% CI, 1.101 to 2.851) and large-size tumors (>2 cm in the greatest
      dimension; OR, 1.644; 95% CI, 1.083 to 2.493; AOR, 1.728; 95% CI, 1.089 to
      2.741). Based on behavioral exposure of environmental carcinogens, the presence
      of 4 RAGE single-nucleotide polymorphisms (SNPs), combined with betel quid
      chewing and/or tobacco use, greatly augmented the risk of oral cancer. In
      addition, carriers of particular haplotypes of the 4 RAGE SNPs examined are more
      prone to develop oral cancer. These results indicate an involvement of RAGE SNP
      rs1800625 in the development of oral squamous cell carcinoma and implicate the
      interaction between RAGE gene polymorphisms and environmental mutagens as a
      predisposing factor of oral carcinogenesis. 

PMID- 25582441
TI  - The Campylobacter jejuni CprRS two-component regulatory system regulates aspects
      of the cell envelope.
AB  - Campylobacter jejuni is a leading cause of food-borne gastroenteritis in humans.
      It lives commensally in the gastrointestinal tract of animals, and tolerates
      variable conditions during transit/colonization of susceptible hosts. The C.
      jejuni CprRS two-component system contains an essential response regulator
      (CprR), and deletion of the cprS sensor kinase enhances biofilms. We sought to
      identify CprRS-regulated genes and better understand how the system affects
      survival. Expression from the cprR promoter was highest during logarithmic growth
      and dependent on CprS. CprR(D52A) did not support viability, indicating that CprR
      phosphorylation is essential despite the dispensability of CprS. We identified a
      GTAAAC consensus bound by the CprR C-terminus; the Asp52 residue of full-length
      CprR was required for binding, suggesting phosphorylation is required.
      Transcripts differing in expression in DeltacprS compared with wildtype (WT)
      contained a putative CprR binding site upstream of their promoter region and
      encoded htrA (periplasmic protease upstream of cprRS) and peb4 (SurA-like
      chaperone). Consistent with direct regulation, the CprR consensus in the htrA
      promoter was bound by CprR(CTD). Finally, DeltahtrA formed enhanced biofilms, and
      DeltacprS biofilms were suppressed by Mg(2+). CprRS is the first C. jejuni
      regulatory system shown to control genes related to the cell envelope, the first
      line of interaction between pathogen and changing environments.

PMID- 25582440
TI  - KCMF1 (potassium channel modulatory factor 1) Links RAD6 to UBR4 (ubiquitin N
      recognin domain-containing E3 ligase 4) and lysosome-mediated degradation.
AB  - RAD6 is a ubiquitin E2 protein with roles in a number of different biological
      processes. Here, using affinity purification coupled with mass spectrometry, we
      identify a number of new RAD6 binding partners, including the poorly
      characterized ubiquitin E3 ligases KCMF1 (potassium channel modulatory factor 1)
      and UBR4 (ubiquitin N-recognin domain-containing E3 ligase 4), a protein that can
      bind N-end rule substrates, and which was recently linked to lysosome-mediated
      degradation and autophagy. NMR, combined with in vivo and in vitro interaction
      mapping, demonstrate that the KCMF1 C terminus binds directly to RAD6, whereas N
      terminal domains interact with UBR4 and other intracellular vesicle- and
      mitochondria-associated proteins. KCMF1 and RAD6 colocalize at late endosomes and
      lysosomes, and cells disrupted for KCMF1 or RAD6 function display defects in late
      endosome vesicle dynamics. Notably, we also find that two different RAD6A point
      mutants (R7W and R11Q) found in X-linked intellectual disability (XLID) patients
      specifically lose the interaction with KCMF1 and UBR4, but not with other
      previously identified RAD6 interactors. We propose that RAD6-KCMF1-UBR4
      represents a unique new E2-E3 complex that targets unknown N-end rule substrates
      for lysosome-mediated degradation, and that disruption of this complex via RAD6A
      mutations could negatively affect neuronal function in XLID patients. 

PMID- 25582442
TI  - Conversion to a sirolimus-based regimen is associated with lower incidence of BK
      viremia in low-risk kidney transplant recipients.
AB  - BACKGROUND: BK viral nephropathy is an increasingly recognized cause of early
      allograft loss in kidney transplantation. This study aimed to determine whether a
      sirolimus (Sir)-based calcineurin inhibitor-sparing regimen is associated with a
      lower incidence of BK viremia. METHODS: This was a single-center retrospective
      study. Patients were either on tacrolimus (Tac)-based or on Sir-based
      immunosuppression. Conversion from Tac to Sir occurred at or after 3 months if
      patients were <62 years of age, had calculated panel reactive antibodies of <20%,
      and did not have acute early rejection. RESULTS: Incidence of clinically
      significant BK viremia was 17.9% in the Tac group and 4.3% in the Sir group. Cox
      regression multivariate analysis showed that male gender (hazard ratio [HR] =
      2.87) and switch to Sir (HR = 0.333) impacted the incidence of BK viremia. Kaplan
      Meier analysis showed a higher BK-free survival in the Sir group. A trend was
      seen toward shorter time to resolution of BK viremia and lower peak viremia in
      the Sir group. Patients on Sir had a higher estimated glomerular filtration rate
      at each time point; 34% of patients discontinued Sir because of side effects.
      CONCLUSION: Conversion to Sir-based maintenance immunosuppression at or about 3
      months after kidney transplantation correlates with a lower incidence of BK
      viremia.

PMID- 25582443
TI  - Psychophysiological mechanisms underlying response selection in multidimensional
      space.
AB  - In the outside world, response selection often requires the processing of
      information from different spatial dimensions. Yet, most neuroscientific
      approaches to the topic only employ variations in one dimension, namely the
      horizontal left-right axis. Hence, virtually nothing is known about the neuronal
      mechanisms underlying response selection in more than one dimension. We
      investigated this aspect with the help of a two-dimensional flanker task using
      EEG and source localization techniques. The data shows that response selection
      processes are differentially modulated across different dimensions. However, this
      modulation is restricted to conditions imposing increased demands on response
      selection. In such situations, a distributed fronto-parietal network mediates
      intensified conflict monitoring processes as well as response inhibition
      processes. In case response selection is carried out in the horizontal dimension,
      those brain areas are more active than during response selection in the vertical
      dimension. Attentional selection processes were not affected. The study's
      findings are of relevance to our understanding to everyday functioning where
      response selection is usually carried out in two or three dimensions and not a
      single dimension as usually investigated in cognitive neuroscience. 

PMID- 25582444
TI  - Multiple sclerosis in 2014. Progress in MS--classification, mechanisms and
      treatment.
AB  - Scientific progress in multiple sclerosis (MS) research spanned a number of areas
      in 2014, including therapeutics, disease classification, risk management, and
      disease mechanisms. Advances were particularly notable in the field of
      progressive MS. Altogether, the findings move us one step closer to a better
      understanding of this complex disease.

PMID- 25582446
TI  - Parkinson disease. Reduced level of dietary vitamin D is associated with PD.

PMID- 25582447
TI  - Traumatic brain injury in 2014. Progress, failures and new approaches for TBI
      research.
AB  - The past year saw the 40th anniversary of the Glasgow Coma Scale, which continues
      to be effective for monitoring patients with traumatic brain injury. Three new
      clinical trials were completed, but none revealed beneficial interventions. These
      failures have prompted exploration of more-subtle therapy targets, novel disease
      classifications and collaborative research paradigms.

PMID- 25582448
TI  - Hemodialysis catheter insertion using transrenal approach.
AB  - We report a patient suffering from end-stage renal disease (ESRD) because of
      lupus nephritis presented with exhausted vascular access after multiple
      arteriovenous grafts creation and hemodialysis catheters insertion. A rare
      percutaneous transrenal approach was finally used for the insertion of dialysis
      catheter. After 2 years, this hemodialysis catheter was complicated by blockage
      but was successfully replaced by a new catheter via the same site. Our report
      shows that the transrenal route of hemodialysis catheter insertion can provide a
      glimpse of hope for those ESRD patients with exhausted vascular access. 

PMID- 25582449
TI  - Parameters recorded by software of non-invasive ventilators predict COPD
      exacerbation: a proof-of-concept study.
AB  - OBJECTIVE: To assess whether daily variations in three parameters recorded by non
      invasive ventilation (NIV) software (respiratory rate (RR), percentage of
      respiratory cycles triggered by the patient (%Trigg) and NIV daily use) predict
      the risk of exacerbation in patients with chronic obstructive pulmonary disease
      (COPD) treated by home NIV. METHODS: Patients completed the EXACT-Pro
      questionnaire daily to detect exacerbations. The 25th and 75th percentiles of
      each 24 h NIV parameter were calculated and updated daily. For a given day, when
      the value of any parameter was >75th or <25th percentile, the day was marked as
      'abnormal value' ('high value' >75th, 'low value' <25th). Stratified conditional
      logistic regressions estimated the risk of exacerbation when >=2 days (for RR and
      %Trigg) or >=3 days (for NIV use) out of five had an 'abnormal value'. RESULTS:
      Sixty-four patients were included. Twenty-one exacerbations were detected and
      medically confirmed. The risk of exacerbation was increased when RR (OR 5.6, 95%
      CI 1.4 to 22.4) and %Trigg (OR 4.0, 95% CI 1.1 to 14.5) were considered as 'high
      value' on >=2 days out of five. CONCLUSIONS: This proof-of-concept study shows
      that daily variations in RR and %Trigg are predictors of an exacerbation.

PMID- 25582450
TI  - Lessons learned in Germany: in the past decade, Germany has invested a great deal
      of money into science funding schemes that have markedly changed its research
      landscape. Was the money well spent, and how will it be spent in future?

PMID- 25582445
TI  - Axial disability and deep brain stimulation in patients with Parkinson disease.
AB  - Axial motor signs-including gait impairment, postural instability and postural
      abnormalities-are common and debilitating symptoms in patients with advanced
      Parkinson disease. Dopamine replacement therapy and physiotherapy provide, at
      best, partial relief from axial motor symptoms. In carefully selected candidates,
      deep brain stimulation (DBS) of the subthalamic nucleus or globus pallidus
      internus is an established treatment for 'appendicular' motor signs (limb tremor,
      bradykinesia and rigidity). However, the effects of DBS on axial signs are much
      less clear, presumably because motor control of axial and appendicular functions
      is mediated by different anatomical-functional pathways. Here, we discuss the
      successes and failures of DBS in managing axial motor signs. We systematically
      address a series of common clinical questions associated with the preoperative
      phase, during which patients presenting with prominent axial signs are considered
      for DBS implantation surgery, and the postoperative phase, in particular, the
      management of axial motor signs that newly develop as postoperative
      complications, either acutely or with a delay. We also address the possible
      merits of new targets-including the pedunculopontine nucleus area, zona incerta
      and substantia nigra pars reticulata-to specifically alleviate axial symptoms.
      Supported by a rapidly growing body of evidence, this practically oriented Review
      aims to support decision-making in the management of axial symptoms. 

PMID- 25582451
TI  - Opportunities and challenges in the subsoil: pathways to deeper rooted crops.
AB  - Greater exploitation of subsoil resources by annual crops would afford multiple
      benefits, including greater water and N acquisition in most agroecosystems, and
      greater sequestration of atmospheric C. Constraints to root growth in the subsoil
      include soil acidity (an edaphic stress complex consisting of toxic levels of Al,
      inadequate levels of P and Ca, and often toxic levels of Mn), soil compaction,
      hypoxia, and suboptimal temperature. Multiple root phenes under genetic control
      are associated with adaptation to these constraints, opening up the possibility
      of breeding annual crops with root traits improving subsoil exploration.
      Adaptation to Al toxicity, hypoxia, and P deficiency are intensively researched,
      adaptation to soil hardness and suboptimal temperature less so, and adaptations
      to Ca deficiency and Mn toxicity are poorly understood. The utility of specific
      phene states may vary among soil taxa and management scenarios, interactions
      which in general are poorly understood. These traits and issues merit research
      because of their potential value in developing more productive, sustainable,
      benign, and resilient agricultural systems. 

PMID- 25582452
TI  - Decreased photosynthesis in the erect panicle 3 (ep3) mutant of rice is
      associated with reduced stomatal conductance and attenuated guard cell
      development.
AB  - The ERECT PANICLE 3 gene of rice encodes a peptide that exhibits more than 50%
      sequence identity with the Arabidopsis F-box protein HAWAIIAN SKIRT (HWS).
      Ectopic expression of the Os02g15950 coding sequence, driven by the HWS
      (At3g61950) promoter, rescued the hws-1 flower phenotype in Arabidopsis
      confirming that EP3 is a functional orthologue of HWS. In addition to displaying
      an erect inflorescence phenotype, loss-of-function mutants of Os02g15950
      exhibited a decrease in leaf photosynthetic capacity and stomatal conductance.
      Analysis of a range of physiological and anatomical features related to leaf
      photosynthesis revealed no alteration in Rubisco content and no notable changes
      in mesophyll size or arrangement. However, both ep3 mutant plants and transgenic
      lines that have a T-DNA insertion within the Os02g15950 (EP3) gene exhibit
      smaller stomatal guard cells compared with their wild-type controls. This
      anatomical characteristic may account for the observed decrease in leaf
      photosynthesis and provides evidence that EP3 plays a role in regulating stomatal
      guard cell development. 

PMID- 25582453
TI  - Protocol for a multicentre, prospective, population-based cohort study of
      variation in practice of cholecystectomy and surgical outcomes (The CholeS
      study).
AB  - INTRODUCTION: Cholecystectomy is one of the most common general surgical
      operations performed. Despite level one evidence supporting the role of
      cholecystectomy in the management of specific gallbladder diseases, practice
      varies between surgeons and hospitals. It is unknown whether these variations
      account for the differences in surgical outcomes seen in population-level
      retrospective data sets. This study aims to investigate surgical outcomes
      following acute, elective and delayed cholecystectomies in a multicentre,
      contemporary, prospective, population-based cohort. METHODS AND ANALYSIS: UK and
      Irish hospitals performing cholecystectomies will be recruited utilising trainee
      led research collaboratives. Two months of consecutive, adult patient data will
      be included. The primary outcome measure of all-cause 30-day readmission rate
      will be used in this study. Thirty-day complication rates, bile leak rate, common
      bile duct injury, conversion to open surgery, duration of surgery and length of
      stay will be measured as secondary outcomes. Prospective data on over 8000
      procedures is anticipated. Individual hospitals will be surveyed to determine
      local policies and service provision. Variations in outcomes will be investigated
      using regression modelling to adjust for confounders. ETHICS AND DISSEMINATION:
      Research ethics approval is not required for this study and has been confirmed by
      the online National Research Ethics Service (NRES) decision tool. This novel
      study will investigate how hospital-level surgical provision can affect patient
      outcomes, using a cross-sectional methodology. The results are essential to
      inform commissioning groups and implement changes within the National Health
      Service (NHS). Dissemination of the study protocol is primarily through the
      trainee-led research collaboratives and the Association of Upper Gastrointestinal
      Surgeons (AUGIS). Individual centres will have access to their own results and
      the collective results of the study will be published in peer-reviewed journals
      and presented at relevant surgical conferences.

PMID- 25582454
TI  - Clinical values of FDG PET in polymyositis and dermatomyositis syndromes: imaging
      of skeletal muscle inflammation.
AB  - OBJECTIVES: [(18)F] Fluorodeoxyglucose positron emission tomography (FDG PET), a
      standard tool for evaluating malignancies, can also detect inflammatory lesions.
      However, its usefulness in evaluating muscle lesions in polymyositis and
      dermatomyositis syndromes (PM/DM) has not been established. METHODS: 33 patients
      with PM/DM who had undergone FDG PET were retrospectively analysed. FDG uptake
      was visually evaluated (visually identified FDG uptake, vFDG) in 16 regions of
      the body using mediastinum blood vessels as a positivity criterion. We also
      calculated the maximum standardised uptake value (SUVmax) in all four limbs of
      the patients with PM/DM as well as in 22 patients with amyotrophic lateral
      sclerosis (ALS) with similar disabilities. In 24 patients with PM/DM, MRI and FDG
      PET findings were compared. RESULTS: vFDG was observed in multiple muscle lesions
      with varying distributions in two-thirds of the patients with PM/DM, with most
      lesions being symmetrical. The number of vFDG-positive regions strongly
      correlated with the mean SUVmax in all four limbs (p<0.0001). Histological grades
      of biopsied muscles correlated with both the mean SUVmax and number of vFDG
      positive regions. Serum creatine kinase levels were higher in patients with more
      than two vFDG-positive regions than in those with two or less regions (p<0.05).
      While the inflamed muscles showed diffused, patchy or marginal signal
      abnormalities on MRI, FDG uptake was most prominent inside the muscles. Compared
      with ALS, the mean SUVmax was significantly higher in the patients with PM/DM
      (p<0.0001) and showed a striking correlation in the bilateral muscles, reflecting
      symmetrical muscle involvement in PM/DM. CONCLUSIONS: The visual assessment of
      FDG uptake as well as calculation of SUV enabled us to comprehensively evaluate
      skeletal muscle. This method can improve clinical practices and provide insights
      into pathomechanisms of PM/DM.

PMID- 25582457
TI  - Hydrogen bonding in ionic liquids.
AB  - Ionic liquids (IL) and hydrogen bonding (H-bonding) are two diverse fields for
      which there is a developing recognition of significant overlap. Doubly ionic H
      bonds occur when a H-bond forms between a cation and anion, and are a key feature
      of ILs. Doubly ionic H-bonds represent a wide area of H-bonding which has yet to
      be fully recognised, characterised or explored. H-bonds in ILs (both protic and
      aprotic) are bifurcated and chelating, and unlike many molecular liquids a
      significant variety of distinct H-bonds are formed between different types and
      numbers of donor and acceptor sites within a given IL. Traditional more neutral H
      bonds can also be formed in functionalised ILs, adding a further level of
      complexity. Ab initio computed parameters; association energies, partial charges,
      density descriptors as encompassed by the QTAIM methodology (rhoBCP), qualitative
      molecular orbital theory and NBO analysis provide established and robust
      mechanisms for understanding and interpreting traditional neutral and ionic H
      bonds. In this review the applicability and extension of these parameters to
      describe and quantify the doubly ionic H-bond has been explored. Estimating the H
      bonding energy is difficult because at a fundamental level the H-bond and ionic
      interaction are coupled. The NBO and QTAIM methodologies, unlike the total
      energy, are local descriptors and therefore can be used to directly compare
      neutral, ionic and doubly ionic H-bonds. The charged nature of the ions
      influences the ionic characteristics of the H-bond and vice versa, in addition
      the close association of the ions leads to enhanced orbital overlap and covalent
      contributions. The charge on the ions raises the energy of the Ylp and lowers the
      energy of the X-H sigma* NBOs resulting in greater charge transfer, strengthening
      the H-bond. Using this range of parameters and comparing doubly ionic H-bonds to
      more traditional neutral and ionic H-bonds it is clear that doubly ionic H-bonds
      cover the full range of weak through to very strong H-bonds. 

PMID- 25582456
TI  - In vitro anti-inflammatory properties of fermented pepino (Solanum muricatum)
      milk by gamma-aminobutyric acid-producing Lactobacillus brevis and an in vivo
      animal model for evaluating its effects on hypertension.
AB  - BACKGROUND: The objectives of this study were to determine the in vitro anti
      inflammatory and in vivo antihypertensive effects of fermented pepino (Solanum
      muricatum) milk by Lactobacillus brevis with the goal of developing functional
      healthy products. The inflammatory factors of fermented pepino milk with L.
      brevis were assessed in RAW 264.7 macrophages, including nitric oxide (NO)
      production. Inflammatory factor genes of cyclooxygenase (COX)-1 and -2, and tumor
      necrosis factor (TNF)-alpha were also assayed by a reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: Results showed that fermented PE
      inhibited NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells
      with 150 mg mL(-1) fermented PE completely blocking LPS-induced NO production.
      The mRNA expressions of COX-1, COX-2, and iNOS were attenuated by treatment with
      higher concentrations of fermented PE (150 mg/ml). Cells treated with fermented
      pepino extract (PE) (100 ng mL(-1)) exhibited strikingly decreased LPS-induced
      expression of TNF-alpha mRNA. During the feeding trial, rats treated with 10%
      fermented pepino milk (100 ug 2.5 mL(-1)) and 100% fermented pepino milk (1000 ug
      2.5 mL(-1)) exhibited significant decreases in the systolic blood pressure.
      CONCLUSION: Our results showed that fermented pepino milk has wide potential
      applications for development as a health food.

PMID- 25582455
TI  - A glucose carbonate apatite complex exhibits in vitro and in vivo anti-tumour
      effects.
AB  - Tumour targeting nanotechnology has recently made therapeutic progress and
      several therapeutic nanoparticles have been approved for clinical application.
      However, an ideal nanotechnology based therapeutic for solid tumours,
      particularly for systemic administration, still remains a challenge in clinical
      cancer therapy. We previously reported a pH sensitive in vivo delivery system of
      doxorubicin, or microRNA, using carbonate apatite (CA) nanoparticles. To further
      explore utility of CA in cancer therapy, we attempted to transport excess glucose
      into tumour cells by conjugating glucose (Glc) to the nanoparticle. Despite the
      non-toxicity of CA and Glc, the complex (CA-[Glc]) exhibited an unexpected anti
      cancer effect in vitro and in vivo. CA-[Glc] significantly reduced the growth of
      colon cancer cell lines. Intravenous injections successfully suppressed solid
      tumour growth. In mice and monkeys, intravenously injected CA-[Glc] complex
      resulted in no serious abnormalities in body weight or blood chemistry. Because
      cancer cells intensively metabolise glucose than normal cells, treatment of
      cancer using glucose seems paradoxical. However, with the aid of CA, this safe
      and 'sweet' complex may be a novel anti-cancer reagent. 

PMID- 25582458
TI  - Synthesis and characterization of secondary nitrosamines from secondary amines
      using sodium nitrite and p-toluenesulfonic acid.
AB  - We synthesized nitrosamines (R2N-NO) with R = iPr (1), nPr (2), nBu (3), and
      hydroxyethyl (4) from the amine using sodium nitrite/p-toluenesulfonic acid in
      CH2Cl2. The rate of formation of 1-4 increases in the direction
      iPr<nPr<nBu<CH2CH2OH. Compounds 1-3 were obtained as colorless solids, whereas 4
      is a bright yellow liquid. Compounds 1-4 were characterized by elemental
      analysis, MS, IR, and multinuclear NMR ((1)H, (13)C, and (15)N) spectroscopies.
      Additionally, we measured the UV/Vis spectra of all compounds, which show maxima
      of absorption at approximately 221 nm and molar extinction coefficients between
      3043 and 4859 L mol(-1)  cm(-1). We calculated the optimized structures of 1-4
      (B3LYP/6-311+G(d,p)) and computed the NMR spectroscopic chemical shifts and
      infrared frequencies. Furthermore, we carried out a natural bond orbital (NBO)
      analysis of the nitrosamine moiety. Lastly, the compounds described in this work
      are valuable starting materials for the synthesis of 2-tetrazenes with potential
      interest to replace highly toxic hydrazines in rocket propulsion.

PMID- 25582461
TI  - [Reasonable use of new technology to detect genetic disease, improve the level of
      diagnosis and treatment of pediatric nervous system diseases].

PMID- 25582462
TI  - [Rare diseases need efforts of medical workers, let our love be not rare].

PMID- 25582459
TI  - Risk of atypical femoral fracture during and after bisphosphonate use.
AB  - BACKGROUND AND PURPOSE: Use of bisphosphonates in women is associated with higher
      risk of atypical femoral fractures. The risk in terms of timing of use and type
      of bisphosphonate, and in men, remains unclear. PATIENTS AND METHODS: We reviewed
      radiographs of 5,342 Swedish women and men aged 55 years or more who had had a
      fracture of the femoral shaft in the 3-year period 2008-2010 (97% of those
      eligible), and found 172 patients with atypical fractures (93% of them women). We
      obtained data on medication and comorbidity. The risk of atypical fracture
      associated with bisphosphonate use was estimated in a nationwide cohort analysis.
      In addition, we performed a case-control analysis with comparison to 952 patients
      with ordinary shaft fractures. A short report of the findings has recently been
      presented (Schilcher et al. 2014a). Here we provide full details. RESULTS: The
      age-adjusted relative risk (RR) of atypical fracture associated with
      bisphosphonate use was 55 (95% CI: 39-79) in women and 54 (CI: 15-192) in men. In
      bisphosphonate users, women had a 3-fold higher risk than men (RR = 3.1, CI: 1.1
      8.4). Alendronate users had higher risk than risedronate users (RR = 1.9, CI: 1.1
      3.3). The RR after 4 years or more of use reached 126 (CI: 55-288), with a
      corresponding absolute risk of 11 (CI: 7-14) fractures per 10,000 person-years of
      use. The risk decreased by 70% per year since last use. INTERPRETATION: Women
      have a higher risk of atypical femoral fracture than men. The type of
      bisphosphonate used may affect risk estimates and the risk decreases rapidly
      after cessation.

PMID- 25582460
TI  - Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal
      tubule cells and kidneys of a mouse model of sickle cell disease.
AB  - Sickle cell disease (SCD), a hereditary hemolytic disorder is characterized by
      chronic hemolysis, oxidative stress, vaso-occlusion and end-organ damage.
      Hemolysis releases toxic cell-free hemoglobin (Hb) into circulation. Under
      physiologic conditions, plasma Hb binds to haptoglobin (Hp) and forms Hb-Hp
      dimers. The dimers bind to CD163 receptors on macrophages for further
      internalization and degradation. However, in SCD patients plasma Hp is depleted
      and free Hb is cleared primarily by proximal tubules of kidneys. Excess free Hb
      in plasma predisposes patients to renal damage. We hypothesized that
      administration of exogenous Hp reduces Hb-mediated renal damage. To test this
      hypothesis, human renal proximal tubular cells (HK-2) were exposed to HbA (50MUM
      heme) for 24h. HbA increased the expression of heme oxygenase-1 (HO-1), an enzyme
      which degrades heme, reduces heme-mediated oxidative toxicity, and confers
      cytoprotection. Similarly, infusion of HbA (32MUM heme/kg) induced HO-1
      expression in kidneys of SCD mice. Immunohistochemistry confirmed the increased
      HO-1 expression in the proximal tubules of the kidney. Exogenous Hp attenuated
      the HbA-induced HO-1 expression in vitro and in SCD mice. Our results suggest
      that Hb-mediated oxidative toxicity may contribute to renal damage in SCD and
      that Hp treatment reduces heme/iron toxicity in the kidneys following hemolysis.

PMID- 25582463
TI  - [Phenotypes and PRRT2 mutation analysis in families with benign familial
      infantile epilepsy].
AB  - OBJECTIVE: To study the phenotypes and proline-rich transmembrane protein 2
      (PRRT2) mutations in families with benign familial infantile epilepsy (BFIE).
      METHOD: Data of all BFIE probands and their family members were collected from
      Peking University First Hospital between September 2006 and August 2013. Clinical
      phenotypes of affected members were analyzed. Genomic DNA was extracted from
      peripheral blood samples with standard protocol. Mutations in PRRT2 were screened
      using PCR amplification and Sanger sequencing. RESULT: Twenty-nine BFIE families
      were recruited in this study. In total, 110 family members were affected. The age
      of seizure onset of these affected members was between 2 and 12 months (median:
      4.5 months). All probands presented with clusters of seizures. Two probands had
      one seizure induced by diarrhea respectively at 25 months and 31 months. In four
      BFIE families, four family members had a history of febrile seizures. PRRT2
      mutations were found in 17 of the 29 (58.6%) BFIE families. Mutation
      c.649_650insC was detected in 12 of the 17 families with PRRT2 mutations.
      Mutation c.649delC (p.R217EfsX12) was identified in three families. Mutation
      c.323_324delCA (p. T108SfsX25) and c.904_ 905insG (p. D302GfsX39) were detected
      in one family, respectively. CONCLUSION: The minimum seizure onset age of
      affected members in BFIE families was 2 months of age. The seizures often occur
      in clusters. PRRT2 is the major causative gene of BFIE in Chinese families.
      Mutation c.649_650insC is the hotspot mutation of PRRT2. A novel mutation
      c.323_324delCA was first reported in BFIE family. Few affected members with PRRT2
      mutation presented with febrile seizures phenotype.

PMID- 25582464
TI  - [Efficacy and safety of rapamycin in treatment of children with epilepsy
      complicated with tuberous sclerosis].
AB  - OBJECTIVE: To evaluate the therapeutic effect and safety of rapamycin in
      treatment of children with tuberous sclerosis complex (TSC) complicated with
      epilepsy. METHOD: This was an open-label, prospective, self-controlled study.
      From Sep. 2011 to Sep. 2013, 52 patients with the diagnosis of tuberous sclerosis
      complicated with epilepsy receiving rapamycin treatment for at least 24 weeks
      were enrolled. RESULT: Of the 52 children, 34 were male and 18 female. The median
      age at onset of epilepsy was 4.8 months (4 days-49 months), the median age for
      treatment with rapamycin was 27 months (4.5-172.5 months). Ten children had a
      family history of TSC. In 24 children TSC gene detection was carried out, among
      whom TSC1 mutation was detected in 4 cases and TSC2 mutation in 20. Before
      rapamycin therapy, 59.62%, (31/52) patients took more than 3 antiepileptic drugs,
      of whom 10 cases even took more than 5 kinds of antiepileptic drugs. Fifty-two
      patients received rapamycin treatment for 24 weeks, seizure free rate was 25.00%
      (13 cases), the total effective rate was 73.08% (38 cases); 31 cases received
      treatment for 48 weeks, seizure free 6 cases, total effective 23 cases; 17 cases
      accepted treatment for 72 weeks, seizure free 5 cases, total effective 13 cases;
      12 cases received treatment for 96 weeks, seizure free 3 cases, total effective 9
      cases. With the decrease of seizure attacks, use of antiepileptic drug types were
      reduced simultaneously, they had a negative correlation. Before rapamycin
      therapy, the average frequency of seizures was 70.27 times/d, the number of
      antiepileptic drug kinds was 1.30. After 24, 48, 72, 96 weeks' treatment, the
      average seizure frequency was reduced to 1.94-2.80 times /d and the antiepileptic
      drugs were reduced to 0.83-0.97 kinds. On every visit during the follow-up, blood
      and urine routine tests, liver and kidney function test showed no abnormality in
      the 52 cases. The drug dosage was 1 mg/(m(2)*d), average 0.7 mg/d (0.35-1.20
      mg/d). Blood concentrations of rapamycin remained below 10 ug/L (average 6.5
      ug/L). The main side effect was oral ulcer which happened in 23.08% (12/52). The
      oral ulcer would disappeared 2-3 days later. 17.31% (9/52 cases) had upper
      respiratory infection. CONCLUSION: Rapamycin was effective in children with
      tuberous sclerosis and epilepsy with few adverse reactions. The daily dose of
      rapamycin for children patients is 1 mg/m(2), which has a certain effect on
      seizures and a good safety profile.

PMID- 25582465
TI  - [SUCLA2-related encephalomyopathic mitochondrial DNA depletion syndrome: a case
      report and review of literature].
AB  - OBJECTIVE: To analyze the clinical characteristics of SUCLA2-related
      encephalomyopathic mitochondrial DNA depletion syndrome (MDS) in one patient, and
      review the latest clinical research reports. METHOD: Clinical, laboratory and
      genetic data of one case of SUCLA2-related encephalomyopathic MDS diagnosed by
      department of Neurology, Beijing Children's Hospital in November, 2013 were
      reported, and through taking "SUCLA2" as key words to search at CNKI, Wanfang,
      PubMed and the Human Gene Mutation Database (HGMD) professional to date, the
      clinical characteristics of 24 reported cases of SUCLA2-related
      encephalomyopathic MDS in international literature in combination with our case
      were analyzed. RESULT: (1) The patient was 5 years and 9 months old, born as a
      term small for gestational age infant whose birth weight was 2 400 g, and
      presented since birth with severe muscular hypotonia, feeding difficulties,
      failure to thrive, psychomotor retardation and hearing impairment. Until now, he
      still showed severe developmental retardation, together with muscular atrophy,
      thoracocyllosis and scoliosis, and facial features. The patient is the first born
      from consanguineous healthy parents, whose relationship is cousins. Laboratory
      tests showed urinary excretion of mild methylmalonic acid (MMA), elevated plasma
      lactate concentration, and increased C3-carnitine and C4-dicarboxylic-carnitine
      in plasma carnitine ester profiling. MRI showed brain atrophy-like and bilateral
      T2 hyperintensities in bilateral caudate nuclei and putamen. By Next-Generation
      Sequencing (NGS), we identified a novel homozygous missense mutation (c.970G > A)
      in the SUCLA2 in a highly conserved amino acid residue. (2) The total number was
      only 25 with a male to female ratio of 14: 11, and age of onset of 23 was 0-4
      months. The most common clinical features in patients with SUCLA2 mutation were
      permanent hypotonia, muscle atrophy, psychomotor retardation and scoliosis or
      kyphosis. Frequent signs included hearing impairment, hyperkinesia, dystonia or
      athetoid movements, feeding difficulties, growth retardation and ptosis or
      ophthalmoplegia. Epilepsy was occasionally observed. The combination of lactic
      acidemia, mild MMA-uria and increased C3-carnitine and C4-dicarboxylic-carnitine
      in plasma carnitine ester profiling were characteristic markers. MRI showed brain
      atrophy-like and bilateral basal ganglia involvement (mainly the putamen and
      caudate nuclei). Nineteen patients originated from Europe, with 13 of whom
      originated from Faroe Islands that carry a homozygous mutation (c.534+1G>A) in
      SUCLA2. CONCLUSION: SUCLA2-related encephalomyopathic MDS is characterized by
      onset of severe hypotonia in early infancy, feeding difficulties, growth
      retardation, psychomotor retardation and hearing impairment. Metabolic findings
      usually include lactic acidemia, mild MMA-uria and increased C3-carnitine and C4
      dicarboxylic-carnitine in plasma carnitine ester profiling. MRI showed brain
      atrophy-like and bilateral basal ganglia involvement (mainly the putamen and
      caudate nuclei). SUCLA2 pathogenic mutations would confirm the diagnosis.

PMID- 25582467
TI  - [Progress of sudden unexpected death in epilepsy].

PMID- 25582468
TI  - [Progress in respiratory function assessment and management for Duchenne muscular
      dystrophy].

PMID- 25582466
TI  - [Clinical and genetic analysis of a family with Aicardi-Goutieres syndrome and
      literature review].
AB  - OBJECTIVE: Aicardi-Goutieres syndrome (AGS) is a rare early-onset genetic
      encephalopathy. The aim of this study was to explore the clinical, imaging and
      genetic features of a family with AGS, which may contribute to definite
      diagnosis, genetic counseling and prenatal diagnosis of this rare disease in
      China. We summarized the characteristics of AGS through reviewing related
      references. METHOD: Information of the proband and other family members as well
      as their DNA samples were collected. All the exons and exon-intron boundaries of
      pathogenic genes were amplified with PCR and were directly sequenced for genomic
      DNA. And we reviewed the reports of 252 cases. RESULT: (1) The proband was a 6
      years plus 7 months old boy. He presented with severe developmental delay and
      abnormal posture mainly as torsion of limbs. By physical examination he was found
      to have some chilblain-like skin lesions at the end of limbs and microcephaly.
      The CT scan of his head displayed multiple calcification, especially in the basal
      ganglia. The MRI of his head displayed a hypointense signal in T1-weighted (T1W)
      images and a hyperintense signal in T2-weighted (T2W) in cerebral white matter
      and cystic lesions in temporal white matter. The younger sister of the proband
      presented with chilblain-like skin lesions on her face and the end of limbs had
      no developmental delay. The CT of her head showed multiple calcification,
      especially in the basal ganglia. (2) Two mutations were identified in TREX1, one
      was a novel nonsense mutation (c.294_295insA), and the other was a known
      pathogenic mutation (c.868_885del). (3) The common performances of AGS included
      mental retardation [92% (231/252) ], dystonia [75% (189/252)], microcephaly [63%
      (159/252) ], chilblain [42% (106/252) ], basal ganglia calcification [100%
      (252/252)], brain atrophy[88% (222/252)] and cerebral white matter lesions [86%
      (217/252)]. TREX1 [38% (96/252) ] and RNASEH2B [23% (58/252)]are the most common
      pathogenic genes. CONCLUSION: We determined pathogenic gene of these patients
      which is the basis of genetic counseling for this family. c.294_295insA mutation
      is a novel mutation not reported around the world yet.

PMID- 25582469
TI  - [Diagnosis and treatment of Fanconi anemia].

PMID- 25582470
TI  - [Neurocognitive and behavioral functioning in children with sleep- disordered
      breathing].

PMID- 25582471
TI  - [Effect of DNA methylation on the proliferation of leukemia cells regulated by
      miR-34b].
AB  - OBJECTIVE: To study the expression level and CpG island methylation status of miR
      34b in leukemia cell lines and to research the effect of DNA methylation on the
      proliferation of leukemia cells regulated by miR-34b. METHOD: Taqman real-time
      fluorescence quantitative polymerase chain reaction (qRT-PCR) was carried out to
      detect the relative expression of miR-34b in control group (bone marrow cells of
      20 children without blood disease) and 8 leukemia cell lines (U937, HL-60, MV4
      11, M2R, K562, Raji, CCRF, DAMI). Methylation-specific polymerase chain reaction
      (MSP) was carried out to detect the methylation differences of miR-34b in control
      group (Bone marrow cells of 23 children without blood disease), 8 leukemia cell
      lines. HL-60 and K562 were treated with methyltransferase inhibitor (5-aza-2-dC)
      for further detection of its methylation status and expression of miR-34b. Hsa
      miR-34b mimics was transfected into K562 cell by liposome, the transfection
      efficiency was detected by flow cytometry. The cell proliferation of hsa-miR-34b
      transfected group in each stage was measured with CCK-8 assay, and then compared
      with non-transfected group and negative control group. RESULT: The relative
      expression level of miR-34b in the group of children without blood disease and
      the group of leukemia cell lines were 5.22 +/- 1.15, 0.03 +/- 0.03. The results
      showed that, the group of leukemia cell lines was significantly different from
      the control group (t = 4.538, P < 0.01) . Eight leukemia cell lines showed
      methylation, the positive rate of the methyl was 100%. There was no methylation
      in the 23 cases of control group. After leukemia cell lines HL-60 and K562 were
      treated with 5-aza-2-dC, the methylated bands became obviously weakened, and the
      relative expression levels of miR-34b substantially increased 49.5 times and 18.8
      times respectively. After hsa-miR-34b mimics was transfected into K562 cell by
      liposome, its transfection efficiency detected by flow cytometry was 61% and the
      cell proliferation was measured with CCK-8 assay from which it was found that the
      cell proliferation was significantly suppressed compared with the control group
      at 48 h (t = 9.303, P < 0.01), 72 h (t = 65.617, P < 0.01), 96 h (t = 36.878, P <
      0.01) and 120 h (t = 18.748, P < 0.01) in hsa-miR-34b transfected group, with the
      inhibition rate of 12.2% (48 h), 45.7% (72 h), 32.5% (96 h) and 22.9% (120 h).
      CONCLUSION: The hypermethylation of promoter leads to decrease in the expression
      levels of miR-34b in leukemia cell lines, which attenuate mechanism of
      proliferative inhibition may be one of the reasons of occurrence or development
      of childhood leukemia.

PMID- 25582472
TI  - [I73T mutation in the pulmonary surfactant protein C gene associated with
      pediatric interstitial lung disease: a case study and the review of related
      literature].
AB  - OBJECTIVE: To report a case of I73T mutation in the pulmonary surfactant protein
      (SP)-C gene associated with pediatric interstitial lung disease, and study the
      clinical diagnosis and review related literature, to investigate the role of gene
      detection in the diagnosis of interstitial lung disease in infants and children.
      METHOD: The clinical, radiological, and genetic testing information of the case
      was analyzed and related literature was reviewed. RESULT: (1) An 8-month-old girl
      was hospitalized because of cough, tachypnea, continuous oxygen therapy and
      failure to thrive. Physical examination on admission revealed tachypnea, slight
      cyanosis and the three concave sign was positive, respiratory rate of 50
      times/minute, scattered fine crackles could be heard over both lungs, clubbing
      fingers were found. No other abnormalities were noted. Laboratory test results:
      pathogenic examination was negative, multiple blood gas analysis suggested
      hypoxemia. Chest CT showed ground-glass like opacity, diffused tubercle
      infiltration. The I73T mutation in SP-C gene was identified by SP-related gene
      sequencing. (2) The review of related literature: Data of 3 infants with I73T
      mutation in SP-C gene showed that all the 3 cases had tachypnea and dyspnea,
      chest CT revealed diffuse infiltration or diffuse ground glass pattern in lungs,
      the major pathology of lungs was nonspecific interstitial pneumonia (NSIP).
      CONCLUSION: A case of interstitial lung disease with I73T mutation in SP-C gene
      was preliminarily diagnosed in an infant. Gene test provides an important tool in
      the diagnosis of such pediatric interstitial lung disease.

PMID- 25582473
TI  - [Diagnosis of children with occult bronchial foreign body].
AB  - OBJECTIVE: To investigate the clinical manifestation of children with occult
      bronchial foreign body, to analyze the reasons of misdiagnosis, to summarize the
      way of diagnosis and to emphasize the value of bronchoscopy in diagnosis and
      treatment of children with such disease. METHOD: A retrospective analysis of 22
      cases of occult bronchial foreign body diagnosed and treated with bronchoscopy in
      Children's Hospital of Chongqing Medical University during the period from March
      1, 2009 to February 28, 2014. RESULT: Of the 22 cases, 15 were male and 7 female.
      Their age ranged from nine months and eight days to fourteen years and six
      months. The course of disease ranged in length from six days to one year. It took
      us one to thirty-three days in diagnosing the problem. They or their parents all
      denied aspirating foreign body and the patients did not have irritating chokes.
      They did not have tracheal displacement or flapping sound. There were no direct
      signs of bronchial foreign body in their imaging examination. Twenty-one patients
      were diagnosed as pneumonia before bronchoscopy, and the remaining one was
      diagnosed as tuberculosis. All of the patients were complicated with infection;
      atelectasis was found in 15 cases/times, lung consolidation in 10 cases/times,
      emphysema in 4, pleural effusion in 5, bronchiectasis in 4, one case had
      respiratory failure, one case had septicemia. The clinical symptoms were relieved
      in the patients after bronchoscopy, 3 cases were cured, 19 cases were improved.
      CONCLUSION: Occult bronchial foreign body with certain complications and great
      harm is hard to diagnose. We should pay more attention to the important clues,
      such as a child with repeated pulmonary infection, indirect signs of airway
      obstruction and difficult to treat. Early bronchoscopy will be useful to improve
      diagnostics once the vital clue is found.

PMID- 25582474
TI  - [Experience in diagnosis and treatment of asparaginase-associated pancreatitis in
      children].
AB  - OBJECTIVE: To analyze the clinical characteristics and the course of diagnosis
      and therapy of PEG-asparaginase associated pancreatitis (AAP) in childhood, and
      to reveal the pathophysiology of AAP, enhance the ability of diagnosis and
      treament. METHOD: Data of 13 cases with AAP in childhood seen from March 2011 to
      March 2014 were analyzed with regard to clinical manifestations, laboratory
      findings, imaging feature and treatment. RESULT: AAP was found in 12 of acute
      lymphoblastic leukemia (ALL) and 1 of non-Hodgkin's lymphoma (NHL), 8 were boys
      and 5 were girls, with a mean age 6 years. In 12 cases AAP occurred during the
      induction-remission treatment, in 1 case during the maintenance- intensification
      phase. AAP occurred after a median of two doses, and 9 d (median) from the latest
      administration of PEG-asparaginase. The major manifestations of AAP was abdominal
      pain (11/13) . At the time of AAP diagnosis during the first 48 hours the median
      peak serum amylase and serum lipase levels were 559 U/L (range 118-1 585, upper
      normal limit: 125) and 934 U/L (range 221-1 673, upper normal limit: 300). Three
      cases with serum amylase and serum lipase levels above 3 times upper normal limit
      were repeatedly complicated with pancreatic pseudocyst; 11 patients had abnormal
      CT imaging, 8 cases revealed effusion around the pancreas, and 4 cases had
      pseudocyst. Therapy with ulinastatin, octreotide acetate, glucocorticoid could
      relieve abdominal pain significantly. Three cases underwent abdominal puncture
      drainage and 5 cases fulfilled nasojejunal nutrition therapy. Nine of them were
      cured, 4 developed pseudocyst, in 2 AAP vanished gradually and 2 died with
      pseudocyst. CONCLUSION: The major manifestations of AAP were abdominal pain, but
      sometimes apparent and sometimes latent. Condition of acute pancreatitis may
      exacerbate rapidly and easily. Early identification had significance. Pancreatic
      pseudocyst suggested a poor prognosis.

PMID- 25582475
TI  - [Relationship between hyperuricemia and primary nephrotic syndrome in children].
AB  - OBJECTIVE: To analyze the relationship between hyperuricemia and primary
      nephrotic syndrome in childhood. METHOD: A retrospective study was carried out in
      107 children with primary nephrotic syndrome. The clinical data were analyzed
      with statistical methods to identify the related factors with hyperuricemia.
      RESULT: The morbidity of hyperuricemia in children with primary nephrotic
      syndrome was 45% (48/107). Compared to those in normal serum uric acid group, the
      incidence of hypertension (33%, 16/48), serum triglyceride [2.59(1.62-3.87)
      mmol/L], creatinine [43.85(33.38-56.38)mmol/L], urea [6.11(3.77-8.40)mmol/L] and
      blood uric acid/creatinine ratio [9.30(7.03-12.72)] increased while creatinine
      clearance rate [141.74(103.57-160.97)ml/(min.1.73 (2))] decreased in
      hyperuricemia group. CONCLUSION: Hyperuricemia in children with primary nephrotic
      syndrome correlated with the increase of serum creatinine, urea and blood uric
      acid/creatinine ratio, the decrease of creatinine clearance rate and the
      occurance of hypertension.

PMID- 25582476
TI  - [Clinical features of pyruvate dehydrogenase complex deficiency and gene testing
      in one case].
AB  - OBJECTIVE: To analyze the clinical characteristics and genetype of one children
      who had been diagnosed with pyruvate dehydrogenase complex deficiency. METHOD:
      Comprehensive analyses of this case were performed, including clinical symptoms,
      signs, biochemical examinations and therapeutic effects. The eleven exons and
      splicing areas of PDHA1 were amplified with genomic DNA from whole blood. And
      variations were investigated by sequencing the PCR product. The patient was
      diagnosed with pyruvate dehydrogenase complex deficiency by sequence analysis of
      PDHA1 gene. RESULT: The patient was a 2 years and 4 monthes old boy. He presented
      with muscle hypotonia and weakness for one year, and experienced recurrent
      episodes of unstable head control, unable to sit by himself or stand without
      support, with persistently hyperlactacidemia. Metabolic testing revealed blood
      lactate 5.37 mmol/L, pyruvate 0.44 mmol/L, and lactate/pyruvate ratio was 12.23.
      MRI of the brain showed hyperintense signals on the T2 and T2 Flair weighted
      images in the basal ganglia bilaterally. Sequence analysis of PDHA1 gene showed a
      G>A point mutation at nucleotide 778, resulting in a substitution of glutarnine
      for arginine at position 263 (R263Q). And the diagnosis of pyruvate dehydrogenase
      complex deficiency was identified. By giving the therapy with ketogenic diet,
      vitamin B(1), coenzyme Q(10) and L-carnitine , the boy was in a stable condition.
      CONCLUSION: The severity and the clinical phenotypes of pyruvate dehydrogenase
      complex deficiency varied. Sequence analysis of PDHA1 gene revealed a 788G>A
      (R263Q) mutation. Patients who presented with unexplained muscle hypotonia,
      weakness and hyperlactacidemia could be diveded by gene analysis. And appropriate
      treatment can improve the quality of life.

PMID- 25582477
TI  - [Maturity-onset diabetes of the young 2 with a novel mutation of glucokinase gene
      in a Chinese boy and the clinical follow-up].
AB  - OBJECTIVE: To explore the clinical and gene mutation characteristics of a child
      with maturity-onset diabetes of the young 2 (MODY2). METHOD: The clinical and
      follow-up data of 1 patient with MODY2 were reviewed. GCK mutational analysis was
      performed by PCR and direct sequencing in the proband and his family members.
      RESULT: The 9 years and 6 months old boy was referred to our department for short
      stature and mild hyperglycemia. His fasting blood glucose was elevated to 7.4-7.8
      mmol/L, hemoglobin A1C 6.7%. His height was 122 cm (-2 s), weight 25 kg (-1 s),
      body mass index (BMI) 16.8 kg/m(2). His physical exam was unremarkable without
      dysmorphic features or acanthosis nigricans. The oral glucose tolerance test
      (OGTT) showed fasting glucose 8.17 mmol/L, insulin <2.0 mU/L, 2 h glucose 8.69
      mmol/L, insulin 5.06 mU /L. The boy was treated with insulin injection for half a
      year. His fasting blood glucose was stable at 5.6-8.5 mmol/L, hemoglobin A1C 6.7%
      6.8%. His mother's fasting blood glucose was 6.86 mmol/L, OGTT 2 h blood glucose
      10.36 mmol/L, hemoglobin A1C 6.8%. GCK sequence revealed a novel GCK mutation
      c.34_44+15del26 in the proband and his mother, which was co-segregated with
      diabetes. The boy's treatment was shifted from insulin injection to diet and
      exercise after the diagnosis of MODY2 was confirmed. Being followed up for 2 and
      a half years, his fasting blood glucose was stable at 4.6-8.0 mmol/L and
      hemoglobin A1C 6.8%-7.1%. CONCLUSION: The clinical features of MODY2 are
      persistent and stable fasting hyperglycemia over a period of months or years and
      small blood glucose increment (less than 3 mmol/L) after an OGTT (2 h glucose
      fasting glucose). We identified a novel c.34_44+15del26 mutation in GCK which co
      segregated with diabetes phenotype in this family.

PMID- 25582478
TI  - [Report of a case with severe hand, foot mouth disease and acute necrotizing
      enterocolitis].

PMID- 25582479
TI  - [Analysis of two cases with idiopathic infantile arterial calcification].

PMID- 25582480
TI  - [BCR-ABL T315I mutant acute lymphoblastic leukemia in 3 children].

PMID- 25582481
TI  - [Summary of the 17th national conference of pediatric hematology].

PMID- 25582482
TI  - Mapping the membrane topography of the TH6-TH7 segment of the diphtheria toxin T
      domain channel.
AB  - Low pH triggers the translocation domain of diphtheria toxin (T-domain), which
      contains 10 alpha helices, to insert into a planar lipid bilayer membrane, form a
      transmembrane channel, and translocate the attached catalytic domain across the
      membrane. Three T-domain helices, corresponding to TH5, TH8, and TH9 in the
      aqueous crystal structure, form transmembrane segments in the open-channel state;
      the amino-terminal region, TH1-TH4, translocates across the membrane to the trans
      side. Residues near either end of the TH6-TH7 segment are not translocated,
      remaining on the cis side of the membrane; because the intervening 25-residue
      sequence is too short to form a transmembrane alpha-helical hairpin, it was
      concluded that the TH6-TH7 segment resides at the cis interface. Now we have
      examined this segment further, using the substituted-cysteine accessibility
      method. We constructed a series of 18 mutant T-domains with single cysteine
      residues at positions in TH6-TH7, monitored their channel formation in planar
      lipid bilayers, and probed for an effect of thiol-specific reagents on the
      channel conductance. For 10 of the mutants, the reagent caused a change in the
      single-channel conductance, indicating that the introduced cysteine residue was
      exposed within the channel lumen. For several of these mutants, we verified that
      the reactions occurred primarily in the open state, rather than in the flicker
      closed state. We also established that blocking of the channel by an amino
      terminal hexahistidine tag could protect mutants from reaction. Finally, we
      compared the reaction rates of reagent added to the cis and trans sides to
      quantify the residue's accessibility from either side. This analysis revealed
      abrupt changes in cis- versus trans-side accessibility, suggesting that the TH6
      TH7 segment forms a constriction that occupies a small portion of the total
      channel length. We also determined that this constriction is located near the
      middle of the TH8 helix. 

PMID- 25582483
TI  - Quality by design in the chiral separation strategy for the determination of
      enantiomeric impurities: development of a capillary electrophoresis method based
      on dual cyclodextrin systems for the analysis of levosulpiride.
AB  - Quality by design (QbD) concepts, in accordance with International Conference on
      Harmonisation Pharmaceutical Development guideline Q8(R2), represent an
      innovative strategy for the development of analytical methods. In this paper QbD
      principles have been comprehensively applied in the set-up of a capillary
      electrophoresis method aimed to quantify enantiomeric impurities. The test
      compound was the chiral drug substance levosulpiride (S-SUL) and the developed
      method was intended to be used for routine analysis of the pharmaceutical
      product. The target of analytical QbD approach is to establish a design space
      (DS) of critical process parameters (CPPs) where the critical quality attributes
      (CQAs) of the method have been assured to fulfil the desired requirements with a
      selected probability. QbD can improve the understanding of the enantioseparation
      process, including both the electrophoretic behavior of enantiomers and their
      separation, therefore enabling its control. The CQAs were represented by
      enantioresolution and analysis time. The scouting phase made it possible to
      select a separation system made by sulfated-beta-cyclodextrin and a neutral
      cyclodextrin, operating in reverse polarity mode. The type of neutral
      cyclodextrin was included among other CPPs, both instrumental and related to
      background electrolyte composition, which were evaluated in a screening phase by
      an asymmetric screening matrix. Response surface methodology was carried out by a
      Doehlert design and allowed the contour plots to be drawn, highlighting
      significant interactions between some of the CPPs. DS was defined by applying
      Monte-Carlo simulations, and corresponded to the following intervals: sulfated
      beta-cyclodextrin concentration, 9-12 mM; methyl-beta-cyclodextrin concentration,
      29-38 mM; Britton-Robinson buffer pH, 3.24-3.50; voltage, 12-14 kV. Robustness of
      the method was examined by a Plackett-Burman matrix and the obtained results,
      together with system repeatability data, led to define a method control strategy.
      The method was validated and was finally applied to determine the enantiomeric
      purity of S-SUL in pharmaceutical dosage forms.

PMID- 25582484
TI  - Monitoring of atmospheric gaseous and particulate polycyclic aromatic
      hydrocarbons in South African platinum mines utilising portable denuder sampling
      with analysis by thermal desorption-comprehensive gas chromatography-mass
      spectrometry.
AB  - Concentrations of diesel particulate matter and polycyclic aromatic hydrocarbons
      (PAHs) in platinum mine environments are likely to be higher than in ambient air
      due to the use of diesel machinery in confined environments. Airborne PAHs may be
      present in gaseous or particle phases each of which has different human health
      impacts due to their ultimate fate in the body. Here we report on the
      simultaneous sampling of both phases of airborne PAHs for the first time in
      underground platinum mines in South Africa, which was made possible by employing
      small, portable denuder sampling devices consisting of two polydimethylsiloxane
      (PDMS) multi-channel traps connected in series separated by a quartz fibre
      filter, which only require small, battery operated portable personal sampling
      pumps for air sampling. Thermal desorption coupled with comprehensive gas
      chromatography-mass spectrometry (TD-GC*GC-TofMS) was used to analyse denuder
      samples taken in three different platinum mines. The samples from a range of
      underground environments revealed that PAHs were predominantly found in the gas
      phase with naphthalene and mono-methylated naphthalene derivatives being detected
      at the highest concentrations ranging from 0.01 to 18 MUg m(-3). The particle
      bound PAHs were found in the highest concentrations at the idling load haul dump
      vehicle exhausts with a dominance of fluoranthene and pyrene. Particle associated
      PAH concentrations ranged from 0.47 to 260 ng m(-3) and included
      benzo[k]fluoranthene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene and
      benzo[ghi]perylene. This work highlights the need to characterise both phases in
      order to assess occupational exposure to PAHs in this challenging sampling
      environment.

PMID- 25582485
TI  - Determination of selenium urinary metabolites by high temperature liquid
      chromatography-inductively coupled plasma mass spectrometry.
AB  - The coupling of high temperature liquid chromatography (HTLC) and inductively
      coupled plasma mass spectrometry (ICPMS) for the determination of selenium
      metabolites in urine samples is reported for the first time. In order to achieve
      "ICPMS-friendly" chromatographic conditions, the retention on a graphite
      stationary phase of the major selenium urinary metabolites using only plain water
      with 2% methanol as the mobile phase was investigated. Under the optimal
      conditions (T=80 degrees C, Ql=1.2 mL min(-1)), methyl 2-acetamido-2-deoxy-1
      seleno-beta-d-galactopyranoside (selenosugar 1), methyl 2-acetamido-2-deoxy-1
      seleno-beta-d-glucosopyranoside (selenosugar 2) and trimethylselenonium ion were
      efficiently separated in less than 7 min, without any interferences due to other
      common selenium species (selenite, selenate, selenocystine and selenomethionine)
      or detectable effect of the urine matrix. The limits of detection were 0.3-0.5 ng
      Se mL(-1), and the precision of the analytical procedure was better than 3%
      (RSD%, n=5). The HTLC-ICPMS method was applied to the analysis of urine samples
      from two volunteers before and after ingestion of Brazil nuts or selenium
      supplements. The developed procedure proved to be adequate for the analytical
      task, providing results consistent with previous studies.

PMID- 25582486
TI  - Direct sample introduction gas chromatography and mass spectrometry for the
      determination of phthalate esters in cleaning products.
AB  - A method using direct sample introduction (DSI) coupled to gas chromatography
      mass spectrometry (GC-MS) is developed for the determination of six phthalate
      esters (dimethyl, diethyl, dibutyl, butylbenzyl, diethylhexyl and dioctyl
      phthalate) in cleaning products. The different variables involved in the DSI
      step, including venting time and temperature, vaporisation time and temperature,
      injector heating temperature and gas flow rate and pressure, were evaluated and
      optimised using Taguchi orthogonal arrays. The proposed method, using calibration
      against methanolic standards, showed good linearity in the 0.05-15 MUg g(-1)
      range and good repeatability, with RSD values ranging from 3.5% to 5.7%.
      Quantification limits between 0.010 and 0.041 MUg g(-1), depending on the
      compound, were attained, while recovery assays provided values from 83% to 115%.
      Twenty-seven cleaning products were analysed using the DSI-GC-MS method, being
      four phthalates (dimethyl, diethyl, dibutyl and diethylhexyl phthalate) found in
      fourteen of them at concentration levels in the 0.1-21 MUg g(-1) range. Compared
      with the most common GC injection technique, which uses the split/splitless
      injector, the proposed DSI procedure provided larger peak areas and lower
      detection limits, as result of the greater injected volume and reduction in
      noise.

PMID- 25582487
TI  - Green analytical method development for statin analysis.
AB  - Green analytical chemistry method was developed for pravastatin, fluvastatin and
      atorvastatin analysis. HPLC/DAD method using ethanol-based mobile phase with
      octadecyl-grafted silica with various grafting and related-column parameters such
      as particle sizes, core-shell and monolith was studied. Retention, efficiency and
      detector linearity were optimized. Even for column with particle size under 2
      MUm, the benefit of keeping efficiency within a large range of flow rate was not
      obtained with ethanol based mobile phase compared to acetonitrile one. Therefore
      the strategy to shorten analysis by increasing the flow rate induced decrease of
      efficiency with ethanol based mobile phase. An ODS-AQ YMC column, 50 mm * 4.6 mm,
      3 MUm was selected which showed the best compromise between analysis time, statin
      separation, and efficiency. HPLC conditions were at 1 mL/min, ethanol/formic acid
      (pH 2.5, 25 mM) (50:50, v/v) and thermostated at 40 degrees C. To reduce solvent
      consumption for sample preparation, 0.5mg/mL concentration of each statin was
      found the highest which respected detector linearity. These conditions were
      validated for each statin for content determination in high concentrated hydro
      alcoholic solutions. Solubility higher than 100mg/mL was found for pravastatin
      and fluvastatin, whereas for atorvastatin calcium salt the maximum concentration
      was 2mg/mL for hydro-alcoholic binary mixtures between 35% and 55% of ethanol in
      water. Using atorvastatin instead of its calcium salt, solubility was improved.
      Highly concentrated solution of statins offered potential fluid for per Buccal
      Per-Mucous((r)) administration with the advantages of rapid and easy passage of
      drugs.

PMID- 25582488
TI  - Identification of cytotoxic and anti-inflammatory constituents from the bark of
      Toxicodendron vernicifluum (Stokes) F.A. Barkley.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Toxicodendron vernicifluum (Stokes) F.A. Barkley
      (Anacardiaceae) has traditionally been used as a food supplement and in
      traditional herbal medicine to treat inflammatory diseases and cancers for
      centuries in Korea. This study was designed to isolate the bioactive constituents
      from the ethanol extract of Toxicodendron vernicifluum bark and evaluate their
      cytotoxic and anti-inflammatory activities. MATERIAL AND METHODS: Bioassay-guided
      fractionation and chemical investigation of the ethanol extract of Toxicodendron
      vernicifluum bark resulted in the isolation and identification of three new
      polyphenols (1-3) and six flavonoids (4-9). The structures of the isolated
      compounds were elucidated by spectroscopic analysis, including 1D and 2D nuclear
      magnetic resonance (NMR) ((1)H, (13)C, COSY, HMQC and HMBC experiments), and high
      resolution (HR)-mass spectrometry, and their absolute configurations were further
      confirmed by chemical methods and circular dichroism (CD) data analysis.
      Compounds 1-9 were evaluated for their antiproliferative activities against four
      human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15), and anti
      inflammatory activities by measuring nitric oxide (NO) levels in the medium of
      murine microglia BV-2 cells. RESULTS: The isolated compounds were characterized
      as in the following: three new polyphenols, rhusopolyphenols G-I (1-3) and six
      flavonoids including two aurones, 2-benzyl-2,3',4',6-tetrahydroxybenzo[b]furan
      3(2H)-one (4), sulfuretin (5), two dihydroflavonols, (+)-(2S,3R)-fustin (6), (+)
      epitaxifolin (7), one chalcone, butein (8), and one flavonol, fisetin (9). The
      published NMR assignments of 4 were corrected by the detailed analysis of
      spectroscopic data in this study. Among the tested compounds, compounds 4-9
      showed antiproliferative activity against the tested cells, with IC50 values of
      4.78-28.89 MUM. Compounds 5 and 8 significantly inhibited NO production in
      lipopolysaccharide (LPS)-stimulated BV-2 cells with IC50 values of 23.37 and
      11.68 MUM, respectively. CONCLUSIONS: Polyphenols including flavonoids were one
      of the main constituents of Toxicodendron vernicifluum bark, and activities
      demonstrated by the isolated compounds support the ethnopharmacological use of
      Toxicodendron vernicifluum as anti-cancer and/or anti-inflammatory agents.

PMID- 25582489
TI  - GABAA/benzodiazepine receptor complex mediates the anxiolytic-like effect of
      Montanoa tomentosa.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Montanoa tomentosa also named Cihuapatli is a
      native plant of Mexico that has been used in traditional medicine for the last
      five centuries mainly as a remedy for reproductive impairments. However, there
      are reports indicating that this plant was also consumed by Mexican ancient
      people for its relaxing properties. In order to corroborate this information, the
      present study was conducted to evaluate the effect of Montanoa tomentosa
      lyophilisate (MT) on rat's anxiety-like behavior and to analyze its mechanism of
      action. MATERIALS AND METHODS: The anxiolytic-like action of MT (1.5, 3.0, 6.0
      and 12.0 mg/kg) was investigated in male Wistar rats tested in three animal
      models of anxiety: the burying behavior, the elevated plus maze and the hole
      board tests. As a positive control, the anti-anxiety effects of different doses
      of the selective GABAA receptor agonist muscimol were also analyzed. In order to
      evaluate the participation of the GABAA and oxytocin receptors in the anxiolytic
      like actions of MT, the GABAA receptors blockers picrotoxin (0.25 and 0.50
      mg/kg), bicuculline (2.0 mg/kg) and flumazenil (5.00 and 10.0 mg/kg), the
      neurosteroid inhibitor finasteride (50.0 and 100 mg/kg) and the oxytocin receptor
      antagonist atosiban (0.25 ug) were used. Finally, to evaluate general activity,
      and motor coordination, the open field and rota-rod tests were used. RESULTS: MT
      at 3.0 mg/kg showed anxiolytic-like effects in the three anxiety paradigms
      without affecting reactivity, general motor activity or motor coordination;
      however, at higher doses sedative effects were observed. Picrotoxin (0.25 and
      0.50 mg/kg), flumazenil (10.0 mg/kg) and finasteride (100 mg/kg) antagonized the
      anxiolytic-like actions of MT in the burying behavior test. In the plus maze and
      hole-board tests bicuculline (2.0 mg/kg) blocked the effects of the plant as
      well. Atosiban (0.25 ug) did not antagonize the anxiolytic-like actions of MT.
      CONCLUSIONS: The results corroborate the anxiolytic-like actions of Montanoa
      tomentosa and suggest that this effect is mediated through GABAA receptors but
      not oxytocin receptors.

PMID- 25582490
TI  - Investigation of the active components in Tripterygium wilfordii leading to its
      acute hepatotoxicty and nephrotoxicity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The traditional herbal medicine Tripterygium
      wilfordii Hook. f. (TW) has been widely used for the treatment of rheumatoid
      arthritis and autoimmune disease in the clinic. However, adverse reactions of TW
      including hepatotoxicity and nephrotoxicity have been frequently reported.
      Terpenes and alkaloids are among the most important active components in TW.
      Triptolide (TP), a major terpene in TW, has been found to induce toxicity, and
      metabolic pathways could lead to detoxification of TP. In this study, whether
      other major terpenes or alkaloids in TW contribute to its toxicity was
      investigated. The role of metabolic eliminations in their potential
      detoxification process was also evaluated. MATERIALS AND METHODS: The toxicity of
      TW and its five major active components (one terpene and four alkaloids) in mice
      was evaluated in terms of mortality and blood biochemical levels (ALT, AST, BUN
      and CREA). TP was used as a positive control. Metabolic pathways leading to
      potential detoxification of TW or its two representative components (triptonide
      and wilforgine) were evaluated in glutathione (GSH)-depleted (treated with L
      buthionine-S,R-sulfoxinine, BSO) and aminobenzotriazole (ABT; a nonspecific
      inhibitor for P450s)-treated mice. RESULTS: In normal mice, the major metabolic
      pathways for the terpene compounds TP and triptonide (TN) were hydroxylation and
      cysteine conjugation, and the alkaloid wilforgine (WG) mainly underwent oxidative
      metabolism and hydrolysis. In ABT/BSO-treated mice, the hydroxylated metabolites
      of TP, TN and WG were found at a lower level than normal mice, and the level of
      cysteine conjugates of TN increased probably due to the stress response. Compared
      with normal mice, mortality and levels of ALT (but not BUN) were significantly
      higher (P<0.01) in TW (or TP)-treated mice (1.2 mg kg(-1)), indicating the acute
      toxicity (may not nephrotoxicity) of TW and its active component TP. Pretreatment
      with ABT and/or BSO increased the acute toxicity (including hepatotoxicity and
      nephrotoxicity) caused by TW or TP. No significant toxicity was found for TN or
      four alkaloids in normal mice or ABT/BSO-treated mice. CONCLUSIONS: TP was
      probably the main contributor to the toxicity of TW, and the terpene TN and
      alkaloids in TW may be of no toxicological concern at dosage levels up to 20-fold
      of the therapeutic dose. Metabolic eliminations to less reactive metabolites
      implied a high potential for detoxification of TW, and caution should be taken
      for TW clinical use during co-administration with other CYP inhibitors or GSH
      depleting agents.

PMID- 25582491
TI  - Improved blood-brain barrier distribution: effect of borneol on the brain
      pharmacokinetics of kaempferol in rats by in vivo microdialysis sampling.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferol (KA) exists in a variety of herbal
      medicines. In vitro and in vivo studies have focused on the anti-Alzheimer effect
      of KA. However, little is known about its brain pharmacokinetic profile. The
      accumulated amount of KA in brain is very low because of the protection of blood
      brain barrier (BBB). Borneol (BO) is a classical aromatic refreshing traditional
      Chinese medicine and commonly used as an adjuvant component of traditional
      Chinese medicines (e.g. compound Danshen dropping pills) in the treatment of
      cardiovascular and cerebrovascular diseases. According to the basic theories of
      traditional Chinese medicine, BO is called an "upper guiding drug", which can
      guide other components to the targeting tissues or organs in the upper part of
      the body, especially in the brain. MATERIALS AND METHODS: The probes for blood
      and brain sampling were implanted within the jugular vein/right atrium and right
      hippocampus of SD rats, respectively. Rats were intravenous administered of KA
      (25 mg/kg) alone or combined with BO (15, 30 mg/kg) via caudal vein. The blood
      and brain microdialysates were collected every 15 min for 180 min and every 30
      min for 180-300 min. A selective and sensitive high performance liquid
      chromatography-chemiluminescence method was developed for the determination of
      unbound KA in rat blood and brain microdialysates, which can be converted to
      their actual free-form concentrations based on the in vivo relative recoveries of
      KA across microdialysis probes. RESULTS: KA quickly crossed the BBB to enter the
      extracellular fluid of hippocampus and reached the maximum concentration of 0.11
      MUg/mL within 30 min. The brain bioavailability and brain delivery of KA
      evidently increased with the co-administration of 15 and 30 mg/kg of BO. The AUC0
      inf of KA in brain increased 1.84 and 2.19 times, and the Cmax of KA in brain
      increased 2.09 and 3.18 times than that without BO, respectively. In addition,
      the brain-to-blood distribution ratio of KA increased by 48.68% and 57.97%
      compared with that without BO. However, no significant difference in the T1/2 of
      unbound KA in blood aserved between three groups. CONCLUSIONS: BO can enhance the
      BBB permeability and improve the transportation of KA to brain. The dose
      dependent effect of BO on the brain pharmacokinetic parameters of KA was
      observed. This co-administration strategy can be designed to enhance the brain
      accumulation of other neuropsychiatric medications.

PMID- 25582492
TI  - Solvent- and phase-controlled photochirogenesis. Enantiodifferentiating
      photoisomerization of (Z)-cyclooctene sensitized by cyclic nigerosylnigerose
      based nanosponges crosslinked by pyromellitate.
AB  - Cyclic nigerosylnigerose (CNN), a saucer-shaped cyclic tetrasaccharide with a
      shallow concave surface, was reacted with pyromellitic dianhydride in 1:2 and 1:4
      ratios to give two CNN-based polymers of different degrees of crosslinking, both
      of which swelled upon soaking in water, acting as a 'nanosponge' (NS). These NSs
      evolved several phases from isotropic solution to flowing and rigid gels via
      suspension by gradually increasing the concentration in water. The CNN-NSs thus
      prepared effectively mediated the enantiodifferentiating photoisomerization of
      (Z)-cyclooctene (1Z) to chiral (E)-isomer (1E). The enantiomeric excess (ee) of
      1E obtained was a critical function of the solvent composition and the phase
      evolved at different CNN-NS concentrations in water. In isotropic solution, the
      enantioselectivity was generally low (-4% to +6% ee) but the chiral sense of 1E
      was inverted by increasing the methanol content. Interestingly, the product's ee
      was controlled more dramatically by the phase evolved, as was the case with the
      cyclodextrin-based nanosponge (CD-NS) reported previously. Thus, the ee of 1E was
      low in solution and suspension, but suddenly leaped at the phase border of
      flowing gel and rigid gel to give the highest ee of 22-24%, which are much higher
      than those obtained with CD-NSs (6-12% ee), revealing the positive roles of the
      chiral void space formed upon gelation of the crosslinked saccharide polymer.

PMID- 25582493
TI  - Cisplatin/Pemetrexed Followed by Maintenance Pemetrexed Versus
      Carboplatin/Paclitaxel/Bevacizumab Followed by Maintenance Bevacizumab in
      Advanced Nonsquamous Lung Cancer: The GOIM (Gruppo Oncologico Italia Meridionale)
      ERACLE Phase III Randomized Trial.
AB  - INTRODUCTION: Cisplatin with pemetrexed (CP) and carboplatin with paclitaxel and
      bevacizumab (CbTB) are standard first-line treatments for patients with advanced
      nonsquamous (NS) non-small-cell lung cancer (NSCLC). Quality of life (QoL) is a
      key objective in the management of advanced NSCLC. Thus, effect on QoL could be
      an additional factor in the choice of treatment. PATIENTS AND METHODS: Patients
      with untreated stage IIIB/IV NS-NSCLC and Eastern Cooperative Oncology Group
      performance status of 0 or 1 were randomized to receive first-line chemotherapy
      with cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2), every 3 weeks, for 6 cycles
      followed by maintenance pemetrexed; or carboplatin area under the curve 6,
      paclitaxel 200 mg/m(2), and bevacizumab 15 mg/kg, every 3 weeks, for 6 cycles
      followed by maintenance bevacizumab. The primary end point was the difference in
      QoL between the 2 treatment arms after 12 weeks of maintenance, measured using
      the EuroQoL 5 Dimensions-Index (EQ5D-I) and EQ5D-visual analogue scale (EQ5D
      VAS). RESULTS: One hundred eighteen patients were randomized to CP (n = 60) or
      CbTB (n = 58). Baseline characteristics were well balanced. The proportion of
      patients evaluable for the primary end point was lower than planned. After 12
      weeks of maintenance, the difference between mean changes in EQ5D-I was 0.137,
      favoring CP (95% confidence interval [CI], -0.02 to 0.29, Wilcoxon P = .078),
      although not statistically significant; and the difference between mean changes
      in EQ5D-VAS was 0.97 (95% CI, -9.37 to 11.31, Wilcoxon P = .41). CONCLUSION:
      Although the study was underpowered because of a small number of patients
      evaluable for the primary end point, QoL did not differ between treatment arms.
      Other factors such as comorbidities and schedule should be used when deciding on
      first-line treatment.

PMID- 25582494
TI  - How to achieve full prophylaxis in young boys with severe haemophilia A:
      different regimens and their effect on early bleeding and venous access.
AB  - To facilitate early prophylaxis, step-up regimens starting prophylaxis with
      infusions 1* week(-1) were introduced. Choice of initial regimen may affect
      outcome. This study aims to classify initial prophylactic regimens and compare
      them on short-term outcome. From the 'European Paediatric Network for Haemophilia
      Management' (PedNet) registry, patients with severe haemophilia A without
      inhibitors, born 2000-2012, receiving prophylaxis were included. Treatment
      centres were classified according to the initial frequency of prophylactic
      infusions and the age at reaching infusions >=3* week(-1) . Bleeding, and central
      venous access device (CVAD) use were compared at age 4 years. In 21 centres with
      363 patients, three regimens were identified: (i) start prophylaxis with >=3*
      week(-1) infusions before age three (full: 19% of centres, 18% of patients); (ii)
      start 1-2* week(-1) , increasing frequency as soon as possible (asap), reaching
      >=3* week(-1) before age three (43% of centres, 36% of patients); (iii) start 1
      2* week(-1) , increasing frequency according to bleeding (phenotype), reaching
      >=3* week(-1) after age three (38% of centres, 46% of patients). Prophylaxis was
      started at median 1.2 years on the full and asap regimen vs 1.8 years on the
      phenotype regimen. Complete prevention of joint bleeds was most effective on the
      full regimen (32% full vs. 27% asap and 8% phenotype), though at the cost of
      using most CVADs (88% full vs. 34% asap and 22% phenotype). The three prophylaxis
      regimens identified had different effects on early bleeding and CVAD use. This
      classification provides the first step towards establishing the optimum
      prophylactic regimen. 

PMID- 25582497
TI  - Photoresponsive self-assemblies based on fatty acids.
AB  - Photoresponsive surfactant system based on fatty acids has been developed by the
      introduction in aqueous solution of a photoacid generator (PAG). Self-assembly
      transitions are triggered by UV irradiation due to a pH change induced by the
      presence of PAG. 

PMID- 25582496
TI  - PD-L1 expression in small cell neuroendocrine carcinomas.
AB  - Small cell lung cancer and extrapulmonary small cell carcinomas are the most
      aggressive type of neuroendocrine carcinomas. Clinical treatment relies on
      conventional chemotherapy and radiotherapy; relapses are frequent. The PD-1/PD
      L1/PD-L2 pathway is a major target of anti-tumour immunotherapy. Aberrant PD-L1
      or PD-L2 expression may cause local immune-suppression. Here we investigated
      expression of PD-1 and its ligands by immunohistochemistry and RNA-seq in small
      cell carcinomas. PD-L1 and PD-1 protein expression were analysed in 94 clinical
      cases of small cell carcinomas (61 pulmonary, 33 extrapulmonary) by
      immunohistochemistry using two different monoclonal antibodies (5H1, E1L3N). RNA
      expression was profiled by RNA-seq in 43 clinical cases. None of the small cell
      carcinomas showed PD-L1 protein expression in tumour cells. PD-L1 and PD-1
      expression was noticed in the stroma: Using immunohistochemistry, 18.5% of cases
      (17/92) showed PD-L1 expression in tumour-infiltrating macrophages and 48% showed
      PD-1 positive lymphocytes (45/94). RNA-seq showed moderate PD-L1 gene expression
      in 37.2% (16/43). PD-L1 was correlated with macrophage and T-cell markers. The
      second PD-1 ligand PD-L2 was expressed in 27.9% (12/43) and showed similar
      correlations. Thus, the PD-1/PD-L1 pathway seems activated in a fraction of small
      cell carcinomas. The carcinoma cells were negative in all cases, PD-L1 was
      expressed in tumour-infiltrating macrophages and was correlated with tumour
      infiltrating lymphocytes. Patients with stromal PD-L1/PD-L2 expression may
      respond to anti-PD-1 treatment. Thus, evaluation of the composition of the tumour
      microenvironment should be included in clinical trials. Besides conventional
      immunohistochemistry, RNA-seq seems suitable for detection of PD-L1/PD-L2
      expression and might prove to be more sensitive. 

PMID- 25582498
TI  - Lateral pharyngeal wall collapse associated with hypoxemia in obstructive sleep
      apnea.
AB  - OBJECTIVES/HYPOTHESIS: Review drug-induced sleep endoscopy (DISE) findings and
      correlate the patterns of airway collapse with body mass index (BMI) and
      objective sleep study respiratory variables, with particular emphasis on oxygen
      desaturation variables. STUDY DESIGN: Retrospective chart review. METHODS: From
      January 2010 to March 2014, 64 patients underwent DISE, and its findings were
      registered using the VOTE (velum, oropharynx, tongue base, epiglottis)
      classification system. Associations were analyzed between DISE, BMI, and
      polysomnographic parameters. RESULTS: Complete lateral oropharyngeal collapse was
      significantly associated with increased severity of obstructive sleep apnea
      (OSA), reflected by a higher oxygen desaturation index, apnea-hypopnea index,
      apnea index, the percent of the total time with oxygen saturation level lower
      than 90%, and minimal oxygen saturation). Complete concentric collapse of the
      velum and complete lateral oropharyngeal collapse were associated with higher BMI
      values. CONCLUSIONS: The results of this study demonstrate a strong association
      between complete lateral oropharyngeal wall collapse and increased OSA severity,
      particularly with objective oximetry measures. Patients with a complete lateral
      oropharyngeal wall collapse may need aggressive treatment strategies because of
      the high probability of subsequent cardiovascular complications. LEVEL OF
      EVIDENCE: 4

PMID- 25582500
TI  - Helsinki score-a novel model for prediction of metastases in adrenocortical
      carcinomas.
AB  - Histopathologic diagnosis of adrenocortical tumors is based on adverse features
      that indicate malignant potential. Proliferation index has served as a
      supplemental tool in assessing the malignant potential of adrenocortical tumors.
      None of the current histologic classification systems can sufficiently accurately
      predict tumors' metastatic potential. We studied 177 consecutive adult patients
      with primary adrenocortical tumors operated on at Helsinki University Central
      Hospital between 1990 and 2003, all patients with a minimum follow-up of 5 years.
      We determined for each tumor the Weiss score and the Weiss revisited score by
      Aubert. Proliferation index was measured by computer-assisted image analysis.
      Each of the 9 Weiss criteria and the proliferation index were then used to
      establish a scoring system to predict the metastatic potential of adrenocortical
      tumors. Use of stepwise regression analysis led us to propose a calculation: 3 *
      mitotic rate (>5/50 high-power fields) + 5 * presence of necrosis + proliferation
      index in the most proliferative area of the tumor. Using a cutoff value of 8.5,
      the new scoring system was able to diagnose metastatic adrenocortical carcinoma
      with 100% sensitivity (confidence interval [CI], 76.8%-100%) and 99.4%
      specificity (CI, 96.6%-100%). The corresponding sensitivity of the Weiss system
      was 100% (CI, 76.8%-100%), and specificity, 90.2% (CI, 84.6%-94.3%), with
      sensitivity of the Weiss revisited system at 100% (CI, 76.8%-100%) and
      specificity at 96.9% (CI, 93.0%-99.0%). The new Helsinki score thus was accurate
      in predicting the metastatic potential of adrenocortical tumors. 

PMID- 25582499
TI  - Undifferentiated carcinoma of the esophagus: a clinicopathological study of 16
      cases.
AB  - Undifferentiated carcinoma of the esophagus is a rare histologic variant of
      esophageal carcinoma. Using criteria based on studies of undifferentiated
      carcinomas arising at other sites, we have collected 16 cases of resected
      esophageal undifferentiated carcinomas. Patients ranged in age from 39 to 84
      years (mean, 65.5 years) and were predominantly male (94%). The tumors were
      characterized by an expansile growth pattern of neoplastic cells organized in
      solid sheets and without significant glandular, squamous, or neuroendocrine
      differentiation. The neoplastic cells had a syncytial-like appearance, little
      intervening stroma, and patchy tumor necrosis. In a subset of cases, the tumor
      cells adopted a sarcomatoid (n = 2), rhabdoid (n = 1), or minor component (<5%)
      of glandular morphology (n = 3). In 1 case, reactive osteoclast-like giant cells
      were found interspersed among the neoplastic cells. Lymphovascular invasion,
      perineural invasion, and lymph node metastases were identified in 88%, 56%, and
      81% of cases, respectively. In 12 (75%) specimens, the background esophageal
      mucosa was notable for Barrett esophagus. Consistent with the epithelial nature
      of these neoplasms, cytokeratin positivity was identified in all cases. In
      addition, SALL4 expression was present in 8 (67%) of 12 cases. Follow-up
      information was available for 15 (94%) of 16 patients, all of whom were deceased.
      Survival after surgery ranged from 1 to 50 months (mean, 11.9 months). Before
      death, 67% patients had documented locoregional recurrence and/or distant organ
      metastases. In summary, esophageal undifferentiated carcinomas are aggressive
      neoplasms and associated with a high incidence of recurrence and/or metastases
      and a dismal prognosis. 

PMID- 25582501
TI  - Utility of ancillary stains for Helicobacter pylori in near-normal gastric
      biopsies.
AB  - Documentation of Helicobacter pylori infection and eradication is important,
      prompting some clinicians and pathologists to request ancillary stains on all
      gastric samples that do not demonstrate H. pylori on initial histologic review.
      Studies evaluating the utility of ancillary stains in patients with minimal
      inflammation are lacking. We used Giemsa, Warthin-Starry, acridine orange, and
      immunohistochemical stains to search for organisms in 56 patients with
      biochemical evidence of H. pylori infection (positive Campylobacter-like organism
      test) and gastric mucosal samples interpreted to be H pylori negative by
      hematoxylin and eosin (H&E). We correlated the findings with severity of
      inflammation and patients' histories of medication use. Nineteen (34%) patients
      had histologically normal mucosae, 22 (39%) had chronic inflammation with or
      without focal activity, and 15 (27%) had chemical gastropathy. Fifty (89%) cases
      were negative for H. pylori with additional stains, and 6 contained bacteria that
      were detected with all 4 ancillary stains and on retrospective review of H&E
      stained sections that also showed chronic inflammation. Eleven (20%) patients
      were taking proton pump inhibitors, and 4 (7%) had previously received H. pylori
      eradication therapy. We conclude that H&E stains demonstrate H. pylori in most
      infected patients, so preemptive stain requests are largely unnecessary. Failure
      to identify bacteria by H&E evaluation generally reflects their absence in biopsy
      material, even among Campylobacter-like organism test--positive patients.
      However, organisms may be overlooked in patients with mild inflammation and in
      those receiving proton pump inhibitor or antibiotic therapy, so one should
      consider ordering ancillary stains to enhance detection of bacteria in these
      settings. 

PMID- 25582502
TI  - A case of PSF-TFE3 gene fusion in Xp11.2 renal cell carcinoma with melanotic
      features.
AB  - Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) with PSF-TFE3 gene fusion
      is a rare neoplasm. Only 22 cases of Xp11.2 RCCs with PSF-TFE3 have been reported
      to date. We describe an additional case of Xp11.2 RCC with PSF-TFE3 showing
      melanotic features. Microscopically, the histologic features mimic clear cell
      renal cell carcinoma. However, the dark-brown pigments were identified and could
      be demonstrated as melanins. Immunohistochemically, the tumor cells were widely
      positive for CD10, human melanoma black 45, and TFE3 but negative for
      cytokeratins, vimentin, Melan-A, microphthalmia-associated transcription factor,
      smooth muscle actin, and S-100 protein. Genetically, we demonstrated PSF-TFE3
      fusion between exon 9 of PSF and exon 5 of TFE3. The patient was free of disease
      with 50 months of follow-up. The prognosis of this type of tumor requires more
      cases because of limited number of cases and follow-up period. Xp11.2 RCC with
      PSF-TFE3 inevitably requires differentiation from other kidney neoplasms.
      Immunohistochemical and molecular genetic analyses are essential for accurate
      diagnosis. 

PMID- 25582503
TI  - Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in
      solitary fibrous tumor with emphasis on the acquisition of highly malignant
      potential.
AB  - The impact of NGFI-A binding protein 2 (NAB2)-signal transducer and activator of
      transcription 6 (STAT6) fusion on the biological behavior and the mechanism of
      acquisition of malignant phenotype in solitary fibrous tumor (SFT) is not well
      understood. We examined variations of the NAB2-STAT6 fusion gene in 40 cases of
      SFT using formalin-fixed, paraffin-embedded tissues and secondary genetic
      alterations of tumor protein p53 (TP53),, platelet-derived growth factor
      receptor, beta polypeptide (PDGFRB), and telomerase reverse transcriptase (TERT)
      promoters. These gene variations were compared with the clinicopathological
      features. The 2-year and 5-year disease-free survival rates (DFSRs) were 91% and
      83%, respectively. All 40 samples demonstrated nuclear staining for STAT6,
      including CD34-negative cases. Moreover, p53-positive staining was associated
      with a lower DFSR and was significantly associated with higher Ki-67 label index,
      higher mitotic rate (mitosis, >4/high-power field), and the presence of nuclear
      atypia/pleomorphism. NAB2-STAT6 fusions were detected in all of the cases; the
      NAB2 exon 4-STAT6 exon 2, the most common genotype, appeared in 18 cases, which
      was associated with thoracic tumor location and the less aggressive phenotype. In
      contrast, tumors with NAB2 exon 6-STAT6 exon 16/18 demonstrated an aggressive
      phenotype. Mutations in TP53 and PDGFRB were detected in 2 and 3 cases
      respectively, and these occurred in a mutually exclusive fashion. TERT promoter
      hot spot mutations were observed in 5 cases, which were associated with shorter
      DFSR. Two dedifferentiated SFT cases harbored both TP53 and TERT promoter
      mutations. TP53 mutations, which result in its overexpression, in combination
      with TERT promoter mutations seem to play an important role in the
      dedifferentiation process. 

PMID- 25582504
TI  - Self-efficacy in providing smoking-cessation services among psychiatric nurses in
      central and southern Taiwan: an exploratory study.
AB  - Smoking by psychiatric patients remains prevalent. The purpose of this cross
      sectional study was to understand the influence of self-efficacy and its
      correlates among psychiatric nurses when providing smoking-cessation services
      (SCS). A convenience sample of 193 nurses from psychiatric institutions was
      obtained. Surveys were conducted using self-report measures regarding SCS
      provided by psychiatric nurses. The survey questions focused on self-efficacy,
      attitude, practical experience, and smoke-free policies, and their implementation
      in the workplace. The participants reported low self-efficacy for providing SCS
      in their self-assessment, as demonstrated by their scores of 55.3 +/- 20.4, on a
      scale of 0 (low confidence) to 100 (high confidence). Using multiple linear
      regressions, statistically-significant, relevant factors included perceived
      provider-related barriers in providing SCS, environmental tobacco smoke exposure,
      the nurse's attitude towards a patient smoking, and the nurse's frequency and
      practical experience in providing SCS. The correlates of this self-efficacy can
      serve as a reference for in-service curriculum planning of SCS by psychiatric
      nurses. In addition, policies to limit exposure to second-hand tobacco smoke
      should be explored. 

PMID- 25582506
TI  - Superior epigastric artery perforator (SEAP) flap: a novel approach to autologous
      breast reconstruction.
AB  - BACKGROUND: Although free tissue breast reconstruction has been increasingly
      used, it remains challenging to perform outside of specialized centers due to
      facility and personnel limitations. We describe a preclinical study highlighting
      the feasibility of a pedicled, superior epigastric artery perforator (SEAP) flap
      utilizing lower abdominal tissues similar to a transverse rectus abdominus
      myocutaneous (TRAM) reconstruction, but with decreased donor-site morbidity.
      METHODS: Fresh cadavers were dissected generating a total of 32 SEAP flaps. These
      flaps were subsequently studied for transposition potential and vascularity
      utilizing computed tomographic (CT) imaging. RESULTS: An obvious, single,
      dominant SEAP was appreciated, and a developed flap was routinely capable of
      reaching either nipple-areola complex with simple interposition. Cadaveric CT
      imaging revealed global contrast filling in each dissected hemi-abdomen tested.
      CONCLUSIONS: We describe a preclinical study utilizing a novel pedicled, SEAP
      flap for aesthetic breast reconstruction. While this will not obviate the use of
      free tissue transfer, it may add to the surgical armamentarium for aesthetic
      restoration in the breast cancer patient.

PMID- 25582505
TI  - Simultaneous determination of bupropion, metroprolol, midazolam, phenacetin,
      omeprazole and tolbutamide in rat plasma by UPLC-MS/MS and its application to
      cytochrome P450 activity study in rats.
AB  - A specific ultra-performance liquid chromatography tandem mass spectrometry
      method is described for the simultaneous determination of bupropion, metroprolol,
      midazolam, phenacetin, omeprazole and tolbutamide in rat plasma with diazepam as
      internal standard, which are the six probe drugs of the six cytochrome P450
      isoforms CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19 and CYP2C9. Plasma samples were
      protein precipitated with acetonitrile. The chromatographic separation was
      achieved using a UPLC(r) BEH C18 column (2.1 * 100 mm, 1.7 um). The mobile phase
      consisted of acetonitrile and water (containing 0.1% formic acid) with gradient
      elution. The triple quadrupole mass spectrometric detection was operated by
      multiple reaction monitoring in positive electrospray ionization. The precisions
      were <13%, and the accuracy ranged from 93.3 to 110.4%. The extraction efficiency
      was >90.5%, and the matrix effects ranged from 84.3 to 114.2%. The calibration
      curves in plasma were linear in the range of 2-2000 ng/mL, with correlation
      coefficient (r(2) ) >0.995. The method was successfully applied to
      pharmacokinetic studies of the six probe drugs of the six CYP450 isoforms and
      used to evaluate the effects of erlotinib on the activities of CYP2B6, CYP2D6,
      CYP3A4, CYP1A2, CYP2C19 and CYP2C9 in rats. Erlotinib may inhibit the activity of
      CYP2B6 and CYP3A4, and may induce CYP2C9 of rats.

PMID- 25582507
TI  - 6-(Bromomaleimido)hexanoic acid as a connector for the construction of multiple
      branched peptide platforms.
AB  - We report on a novel and user-friendly platform based on a bromomaleimide moiety
      to obtain branched peptides. The platform is stable for all SPPS conditions. The
      bromomaleimide core was conjugated to n-copies of thiol-peptide in-solution to
      obtain two/four/eight-armed dendrimers. Using 'n' number of bromomaleimide
      analogues, 2(n) ligands were incorporated at both bromo and ene positions via a
      thioether bond. This method has the advantage of high conversion in a short time,
      thus enabling effortless purification and characterization processes. 

PMID- 25582508
TI  - Metabolomic discovery of novel urinary galabiosylceramide analogs as Fabry
      disease biomarkers.
AB  - Fabry disease is an X-linked, complex, multisystemic lysosomal storage disorder
      presenting marked phenotypic and genotypic variability among affected male and
      female patients. Glycosphingolipids, mainly globotriaosylceramide (Gb(3))
      isoforms/analogs, globotriaosylsphingosine (lyso-Gb(3)) and analogs, as well as
      galabiosylceramide (Ga(2)) isoforms/analogs accumulate in the vascular
      endothelium, nerves, cardiomyocytes, renal glomerular and tubular epithelial
      cells, and biological fluids. The search for biomarkers reflecting disease
      severity and progression is still on-going. A metabolomic study using quadrupole
      time-of-flight mass spectrometry has revealed 22 galabiosylceramide
      isoforms/analogs in urine of untreated Fabry patients classified in seven groups
      according to their chemical structure: (1) Saturated fatty acid; (2) one extra
      double bond; (3) two extra double bonds; (4) hydroxylated saturated fatty acid;
      (5) hydroxylated fatty acid and one extra double bond; (6) hydrated sphingosine
      and hydroxylated fatty acid; (7) methylated amide linkage. Relative
      quantification of both Ga(2) and Gb(3) isoforms/analogs was performed. All these
      biomarkers are significantly more abundant in urine samples from untreated Fabry
      males compared with healthy male controls. A significant amount of Ga(2)
      isoforms/analogs, accounting for 18% of all glycosphingolipids analyzed (Ga(2) +
      Gb(3) and respective isoforms/analogs), were present in urine of Fabry patients.
      Gb(3) isoforms containing saturated fatty acids are the most abundant (60.9%)
      compared with 26.3% for Ga(2). A comparison between Ga(2) isoforms/analogs and
      their Gb(3) counterparts also showed that the proportion of analogs with
      hydroxylated fatty acids is significantly greater for Ga(2) (35.8%) compared with
      Gb(3) (1.9%). These results suggest different biological pathways involved in the
      synthesis and/or degradation of Gb(3) and Ga(2) metabolites.

PMID- 25582509
TI  - A comparison of energy-resolved vibrational activation/dissociation
      characteristics of protonated and sodiated high mannose N-glycopeptides.
AB  - Fragmentation of glycopeptides in tandem mass spectrometry (MS/MS) plays a
      pivotal role in site-specific protein glycosylation profiling by allowing
      specific oligosaccharide compositions and connectivities to be associated with
      specific loci on the corresponding protein. Although MS/MS analysis of
      glycopeptides has been successfully performed using a number of distinct ion
      dissociation methods, relatively little is known regarding the fragmentation
      characteristics of glycopeptide ions with various charge carriers. In this study,
      energy-resolved vibrational activation/dissociation was examined via collision
      induced dissociation for a group of related high mannose tryptic glycopeptides as
      their doubly protonated, doubly sodiated, and hybrid protonated sodium adduct
      ions. The doubly protonated glycopeptide ions with various compositions were
      found to undergo fragmentation over a relatively low but wide range of collision
      energies compared with the doubly sodiated and hybrid charged ions, and were
      found to yield both glycan and peptide fragmentation depending on the applied
      collision energy. By contrast, the various doubly sodiated glycopeptides were
      found to dissociate over a significantly higher but narrow range of collision
      energies, and exhibited only glycan cleavages. Interestingly, the hybrid
      protonated sodium adduct ions were consistently the most stable of the precursor
      ions studied, and provided fragmentation information spanning both the glycan and
      the peptide moieties. Taken together, these findings illustrate the influence of
      charge carrier over the energy-resolved vibrational activation/dissociation
      characteristics of glycopeptides, and serve to suggest potential strategies that
      exploit the analytically useful features uniquely afforded by specific charge
      carriers or combinations thereof. 

PMID- 25582510
TI  - Negative affect mediates the relationship between interpersonal problems and
      binge-eating disorder symptoms and psychopathology in a clinical sample: a test
      of the interpersonal model.
AB  - This study evaluated the validity of the interpersonal model of binge-eating
      disorder (BED) psychopathology in a clinical sample of women with BED. Data from
      a cross-sectional sample of 255 women with BED were examined for the direct
      effects of interpersonal problems on BED symptoms and psychopathology, and
      indirect effects mediated by negative affect. Structural equation modelling
      analyses demonstrated that higher levels of interpersonal problems were
      associated with greater negative affect, and greater negative affect was
      associated with higher frequency of BED symptoms and psychopathology. There was a
      significant indirect effect of interpersonal problems on BED symptoms and
      psychopathology mediated through negative affect. Interpersonal problems may lead
      to greater BED symptoms and psychopathology, and this relationship may be
      partially explained by elevated negative affect. The results of the study are the
      first to provide support for the interpersonal model of BED symptoms and
      psychopathology in a clinical sample of women.

PMID- 25582512
TI  - Emotional disorders in adult mice heterozygous for the transcription factor
      Phox2b.
AB  - Phox2b is an essential transcription factor for the development of the autonomic
      nervous system. Mice carrying one invalidated Phox2b allele (Phox2b(+/-)) show
      mild autonomic disorders including sleep apneas, and impairments in
      chemosensitivity and thermoregulation that recover within 10days of postnatal
      age. Because Phox2b is not expressed above the pons nor in the cerebellum, this
      mutation is not expected to affect brain development and cognitive functioning
      directly. However, the transient physiological disorders in Phox2b(+/-) mice
      might impair neurodevelopment. To examine this possibility, we conducted a
      behavioral test battery of emotional, motor, and cognitive functioning in adult
      Phox2b(+/-) mice and their wildtype littermates (Phox2b(+/+)). Adult Phox2b(+/-)
      mice showed altered exploratory behavior in the open field and in the elevated
      plus maze, both indicative of anxiety. Phox2b(+/-) mice did not show cognitive or
      motor impairments. These results suggest that also mild autonomic control
      deficits may disturb long-term emotional development. 

PMID- 25582513
TI  - Low heart rate response of children with autism spectrum disorders in comparison
      to controls during physical exercise.
AB  - BACKGROUND: The objective of the study was to investigate how the heart rate
      adjusts during different physical tests. Children with autism spectrum disorder
      (ASD) do indeed have a lower cardiac response to specific tests. METHODS: Twenty
      children including 10 subjects with ASD diagnosis and 10 control subjects were
      evaluated using the Eurofit Physical Fitness Test Battery. During the evaluation,
      the heart rate was monitored continuously. In parallel, their parents were
      completed the Vineland Adaptive Behavior Scales. RESULTS: Both groups show the
      same trend of heart rate increase (during exercise and also during the maximum
      effort). However, children with ASD presented a significant lower heart rate
      compared to the control population (p<0.001). Based on Eurofit Physical Fitness
      Test battery, children with ASD showed lower results than controls on plate
      tapping test (p<0.01), vertical and broad jump tests (p<0.01) and also sit up
      test (p<0.01). Moreover, Flamingo balance test showed that the ASD group had a
      higher number of falls (p<0.01). The handgrip test showed that they had a lower
      force (p<0.01) and they also executed the find motor educational course more
      slowly with a significantly higher number of falls, mistakes and omissions
      (p<0.01). CONCLUSIONS: Both groups showed similar trend with the cardiac kinetic
      reflecting the adjustment to the effort. However, the significant heart rate
      decrease of the ASD group during physical test could be due to an alteration of
      the cardiac response. In addition, the scores obtained by children with ASD on
      physical tests confirmed the lack of motor abilities such as balance and
      executive functions.

PMID- 25582511
TI  - Immunoproteomic profile of Trichinella spiralis adult worm proteins recognized by
      early infection sera.
AB  - BACKGROUND: Trichinellosis, a widespread zoonosis, is regarded as an emerging or
      reemerging disease. Effective treatment and prognosis of trichinellosis depends
      on early diagnosis of the infection. The objective of this study was to identify
      sensitive and specific antigens for early diagnosis or effective vaccine antigens
      for preventing infection. METHODS: The somatic proteins of T. spiralis adult
      worms were separated by two-dimensional gel electrophoresis (2-DE). The separated
      proteins were probed with early infection sera from swine or mice infected with
      T. spiralis for 7 days. The primary immunoreactive spots were characterized by
      MALDI-TOF/TOF-MS analysis in combination with bioinformatics. The identified
      proteins were annotated using WEGO based on their functions. The immunodominant
      protein was chosen for expression as recombinant protein in E. coli and the
      purified recombinant protein was used to confirm its antigenicity by Western blot
      with the same infection sera. RESULTS: Approximately 300 spots were separated by
      2-DE, with molecular weights ranging from 10 to 130 kDa, and pI values ranging
      from pH 4 to 10. The sera from swine and mice infected with T. spiralis for 7
      days recognized 64 proteins. MALDI-TOF/TOF-MS analysis identified 55 proteins,
      some with different isoforms. Finally, 40 individual immunoreactive proteins were
      obtained with a wide range of biological functions. Several proteins, such as
      heat shock protein 70, 14-3-3 protein, and cysteine protease could be used as
      immunodiagnostic or vaccine antigens. Among these identified proteins, the highly
      immunodominant Ts14-3-3 was chosen for expression in E. coli and purified
      recombinant Ts14-3-3 was able to be strongly recognized by the same T. spiralis
      infected sera used for identifying these antigens, therefore the most promising
      antigen for early immunodiagnosis of Trichinella infection. CONCLUSIONS: A total
      of 64 proteins from the adult worm were recognized by early infection sera from
      swine and mice infected with T. spiralis for 7 days. Several proteins, are of
      particular interest as immunodiagnostic or vaccine antigens, especially with Ts14
      3-3 as most promising due to its highly immunogenicity during early infection,
      expressed protein can be recognized by Trichinella early infection sera and the
      native Ts14-3-3 expression in both adult and larval stages.

PMID- 25582514
TI  - Effect of a long-term exposure to concentrated sucrose and maltodextrin solutions
      on the preference, appetence, feed intake and growth performance of post-weaned
      piglets.
AB  - Commercial pigs display an innate attraction for sweet taste compounds. However,
      the impact of long-term availability to supplementary carbohydrate solutions on
      their general feeding behavior has not been examined. In this work we assess the
      effect of 12-days exposure to 16% sucrose and 16% maltodextrin solutions on the
      feed intake and growth performance of piglets, and on their preference and
      appetence for sweet or protein solutions. The innate preference of piglets was
      assessed by an initial choice test between 2% sucrose and 2% animal plasma
      solutions for a period of three minutes. Piglets showed higher intake and
      preference for 2% sucrose than for 2% animal plasma. In Experiment 1, piglets
      were then free-offered a 16% sucrose solution as a supplement to the diet,
      showing a higher intake of it than water and a reduction in feed intake and
      weight gain. A similar situation occurred during the last days of free-exposure
      to a 16% maltodextrin solution in Experiment 2. The choice test between 2%
      sucrose and 2% animal plasma solution was repeated after the exposure to the
      concentrated solutions. In both experiments, a reduction in the initial
      preference for 2% sucrose was observed. Similarly, piglets that had previous
      access to the 16% sucrose and 16% maltodextrin solutions showed a decrease in the
      appetence for 2% sucrose in comparison with that for 2% animal plasma, as
      measured by a one-pan test at the end of the experiments. It is concluded that
      long-term exposure to concentrated sucrose and maltodextrin solutions reduces
      feed intake and growth in weanling piglets, and also reverses their innate
      preference and appetence for dilute sweet over protein solutions. 

PMID- 25582515
TI  - Relation between aggression exposure in adolescence and adult posttraumatic
      stress symptoms: Moderating role of the parasympathetic nervous system.
AB  - The present study examines the impact of the parasympathetic nervous system
      (PNS), as measured by respiratory sinus arrhythmia (RSA), on the link between
      family aggression experienced during adolescence and posttraumatic stress
      symptoms during young adulthood. Participants completed retrospective self-report
      measures of interparental aggression and harsh parenting exposure during
      adolescence and measures of current posttraumatic stress symptoms. RSA indexed
      PNS activity. Among females, the three-way interaction between harsh parenting,
      interparental aggression, and resting RSA was significant in accounting for young
      adulthood PTSD symptoms. At higher values of resting RSA and higher levels of
      interparental aggression exposure, harsh parenting experienced during adolescence
      was positively associated with adulthood PTSD symptoms. Among males, adolescent
      aggression exposure and resting RSA did not significantly account for variation
      in adulthood PTSD symptoms. Thus, this study suggests that resting PNS activity
      may play an important role in the relationship between stressors during
      adolescence and later PTSD in females. 

PMID- 25582516
TI  - Does acute exercise affect the performance of whole-body, psychomotor skills in
      an inverted-U fashion? A meta-analytic investigation.
AB  - The primary purpose of this study was to examine, using meta-analytical measures,
      whether research into the performance of whole-body, psychomotor tasks following
      moderate and heavy exercise demonstrates an inverted-U effect. A secondary
      purpose was to compare the effects of acute exercise on tasks requiring static
      maintenance of posture versus dynamic, ballistic skills. Moderate intensity
      exercise was determined as being between 40% and 79% maximum power output (WMAX)
      or equivalent, while >=80% WMAX was considered to be heavy. There was a
      significant difference (Zdiff=4.29, p=0.001, R(2)=0.42) between the mean effect
      size for moderate intensity exercise (g=0.15) and that for heavy exercise size
      (g=-0.86). These data suggest a catastrophe effect during heavy exercise. Mean
      effect size for static tasks (g=-1.24) was significantly different (Zdiff=3.24,
      p=0.001, R(2)=0.90) to those for dynamic/ballistic tasks (g=-0.30). The result
      for the static versus dynamic tasks moderating variables point to perception
      being more of an issue than peripheral fatigue for maintenance of static posture.
      The difference between this result and those found in meta-analyses examining the
      effects of acute exercise on cognition shows that, when perception and action are
      combined, the complexity of the interaction induces different effects to when
      cognition is detached from motor performance. 

PMID- 25582517
TI  - Characterization of attenuated food motivation in high-fat diet-induced obesity:
      Critical roles for time on diet and reinforcer familiarity.
AB  - Prior work using animal models to study the effects of obesogenic diets on food
      motivation have generated inconsistent results, with some reporting increases and
      others reporting decreases in responding on food-reinforced tasks. Here, we
      identified two specific variables that may account for these discrepant outcomes 
      the length of time on the obesigenic diet and the familiarity of the food
      reinforcer - and examined the independent roles of these factors. Time on diet
      was found to be inversely related to food motivation, as rats consuming a 40%
      high-fat diet (HFD) for only 3weeks did not differ from chow-fed rats when
      responding for a sucrose reinforcer on a progressive ratio (PR) schedule, but
      responding was suppressed after 6weeks of ad lib HFD consumption. Explicitly
      manipulating experience with the sucrose reinforcer by pre-exposing half the rats
      prior to 10weeks of HFD consumption attenuated the motivational deficit seen in
      the absence of this familiarity, resulting in obese rats performing at the same
      level as lean rats. Finally, after 8weeks on a HFD, rats did not express a
      conditioned place preference for sucrose, indicating a decrement in reward value
      independent of motivation. These findings are consistent with prior literature
      showing an increase in food motivation for rats with a shorter time consuming the
      obesigenic diet, and for those with more prior experience with the reinforcer.
      This account also helps reconcile these findings with increased food motivation
      in obese humans due to extensive experience with palatable food and suggests that
      researchers engaging in non-human animal studies of obesity would better model
      the conditions under which human obesity develops by using a varied, cafeteria
      style diet to increase the breadth of food experiences. 

PMID- 25582518
TI  - Influence of food volume per mouthful on chewing and bolus properties.
AB  - BACKGROUND: Behaviors relating to food intake, i.e., speed of chewing, number of
      chews, and bite size, are important for decreasing energy intake, which might
      reduce excess body weight and thus metabolic risk. This study aimed at
      investigating the influence of mouthful volume on the number of chews and food
      bolus properties in addition to clarifying appropriate eating behaviors related
      to mouthful volume. METHODS: Fifteen young Japanese women volunteered to
      participate. The subjects were asked to spit the food bolus in a glass dish just
      before swallowing when eating 3 different foods: boiled rice, fish sausage, and
      peanuts. The 3 physical properties of solidity, adhesiveness, and cohesiveness
      were measured in the bolus, and the number of chews was noted. RESULTS: The
      number of chews significantly increased with increasing mouthful volume with all
      3 foods; conversely, the number of chews per unit of food weight (g) decreased
      significantly with boiled rice and fish sausage. Trends were observed for
      solidity and cohesiveness, which varied with increasing mouthful volumes.
      CONCLUSIONS: Decreased mouthful volume resulted in a greater number of chews per
      weight of food and more appropriate bolus properties; therefore, a change in
      mouthful volume could be a useful behavior modification for regulation of energy
      intake.

PMID- 25582519
TI  - Clinical observation of the adverse drug reactions caused by non-ionic iodinated
      contrast media: results from 109,255 cases who underwent enhanced CT examination
      in Chongqing, China.
AB  - OBJECTIVE: To analyse the pattern and factors that influence the incidence of
      adverse drug reactions (ADRs) induced by non-ionic iodinated contrast media and
      to evaluate their safety profiles. METHODS: Data from 109,255 cases who underwent
      enhanced CT examination from 1 January 2008 to 31 August 2013 were analysed. ADRs
      were classified according to the criteria issued by the American College of
      Radiology and the Chinese Society of Radiology. RESULTS: A total of 375 (0.34%)
      patients had ADRs, including 281 mild (0.26%); 80 moderate (0.07%); and 14 severe
      (0.01%) ADRs; no death was found. 302 (80.53%) of the ADRs occurred within 15 min
      after examination. Patients aged 40-49 years (204 cases, 0.43%; p < 0.01) or who
      underwent coronary CT angiography (93 cases, 0.61%; p < 0.01) were at a higher
      risk of ADRs. Female patients (180 cases, 0.40%; p < 0.01) or outpatients had
      significantly higher incidence rates of ADRs. The symptoms and signs of most of
      the ADRs were resolved spontaneously within 24 h after appropriate treatment
      without sequelae. CONCLUSION: The occurrence of ADRs is caused by the combined
      effects of multiple factors. The ADRs induced by non-ionic iodinated contrast
      media are mainly mild ones, while moderate or severe ADRs are relatively rare,
      suggesting that enhanced CT examination with non-ionic iodinated contrast media
      is highly safe, and severe adverse events will seldom occur under appropriate
      care. ADVANCES IN KNOWLEDGE: The study included 109,255 patients enrolled in
      various types of enhanced CT examinations, which could reflect ADR conditions and
      regulations in Chinese population accurately and reliably.

PMID- 25582520
TI  - Magnesium-induced recurarisation after reversal of rocuronium-induced
      neuromuscular block with sugammadex.
AB  - A 61-year-old woman (57 kg, 171 cm) underwent surgery under general anaesthesia
      with desflurane 5.8-6.1 vol. % end-tidal, remifentanil 0.2-0.4 MUg/kg/min and
      rocuronium 35 mg (0.61 mg/kg). On return of the second twitch in the train-of
      four (TOF) stimulation measured by acceleromyography, sugammadex 120 mg (2.1
      mg/kg) was given. After complete neuromuscular recovery, magnesium sulphate 3600
      mg (60 mg/kg) was injected intravenously over 5 min to treat atrial fibrillation.
      This was associated with recurarisation with a nadir [first twitch=25%, TOF ratio
      (TOFR)=67%] 7 min after the start of the magnesium sulphate infusion (magnesium
      plasma level: 2.67 mM). A spontaneous twitch value and a TOFR of >90% were
      observed 45 min after the beginning of the magnesium sulphate infusion under
      general anaesthesia. Rapid infusion of magnesium sulphate may re-establish a
      sugammadex-reversed, rocuronium-induced neuromuscular block during general
      anaesthesia, probably because of the high plasma level of magnesium (2.67 mM).
      Desflurane and a small fraction of unbound rocuronium may amplify the known
      muscle relaxing effects of magnesium. Intravenous injection of magnesium sulphate
      is not recommended in patients after general anaesthesia with neuromuscular
      relaxants, particularly after sugammadex reversal. Quantitative neuromuscular
      monitoring should be used for reversing aminosteroid muscle relaxants with
      sugammadex--particularly in combination with magnesium injection--to prevent post
      operative residual curarisation.

PMID- 25582521
TI  - Sexual dysfunction in 2014: Men enjoy a year of significant progress.

PMID- 25582522
TI  - Increased brain response to appetitive tastes in the insula and amygdala in obese
      compared with healthy weight children when sated.
AB  - OBJECTIVE: There is evidence of altered neural taste response in female
      adolescents who are obese (OB), and in adolescents who are at risk for obesity.
      To further understand risk factors for the development of overeating and obesity,
      we investigated response to tastes of sucrose and water in 23 OB and healthy
      weight (HW) children. METHODS AND DESIGN: Thirteen HW and 10 OB 8-12-year-old
      children underwent functional magnetic resonance imaging while tasting sucrose
      and water. Additionally, children completed an eating in the absence of hunger
      paradigm and a sucrose-liking task. RESULTS: A region of interest analysis
      revealed an elevated BOLD response to taste (sucrose and water) within the
      bilateral insula and amygdala in OB children relative to HW children. Whole-brain
      analyses revealed a group by condition interaction within the paracingulate,
      medial frontal, middle frontal gyri and right amygdala: post hoc analyses
      suggested an increased response to sucrose for OB relative to HW children,
      whereas HW children responded more strongly to water relative to sucrose. In
      addition, OB children, relative to HW, tended to recruit the right putamen as
      well as medial and lateral frontal and temporal regions bilaterally. CONCLUSION:
      This study showed increased reactivity in the amygdala and insula in the OB
      compared with HW children, but no functional differentiation in the striatum,
      despite differences in the striatum previously seen in older samples. These
      findings support the concept of the association between increased neural
      processing of food reward in the development of obesity, and raise the
      possibility that emotional and interoceptive sensitivity could be an early
      vulnerability in obesity.

PMID- 25582525
TI  - Synthetic peptides caged on histidine residues with a bisbipyridyl ruthenium(II)
      complex that can be photolyzed by visible light.
AB  - We report a light-sensitive histidine building block for Fmoc/tBu solid-phase
      peptide synthesis in which the imidazole side chain is coordinated to a ruthenium
      complex. We have applied this building block for the synthesis of caged-histidine
      peptides that can be readily deprotected by irradiation with visible light, and
      demonstrated the application of this approach for the photocontrol of the
      activity of Ni(II)-dependent peptide nucleases.

PMID- 25582524
TI  - Quantitative analysis of immunoglobulin subclasses and subclass specific
      glycosylation by LC-MS-MRM in liver disease.
AB  - Aberrant glycosylation of IgGs has been linked to human diseases, including liver
      disease. In this study, we have quantified plasma immunoglobulins in cirrhosis
      (CIR) and hepatocellular carcinoma (HCC) and employed a novel LC-MS-MRM assay to
      quantify glycoforms of IgG subclasses 1-4. Glycan oxonium ions and peptide-GlcNAc
      fragment ions were utilized to quantify the IgG glycoforms purified by affinity
      chromatography with normalization to the unique peptide for each IgG subclass.
      Our results indicate that HCC patients have increased circulating IgG1, IgG3,
      IgA1, and IgM compared to healthy controls; comparison of HCC and CIR patients
      shows that HCC patients have significantly higher concentration of IgG1 and IgM
      but lower concentration of IgG2. An increase in galactose-deficient core
      fucosylated glycoforms was consistently observed in CIR and HCC patients. The
      FA2G0 and FA2BG0 glycoforms increase approximately 2-fold in all IgG subclasses
      accompanied by a decrease in the FA2G2 glycoform. Fucosylation changes are less
      pronounced but we have detected increased degree of fucosylation in the IgG1 and
      IgG3 glycoforms. In conclusion, we have optimized a sensitive and selective LC-MS
      MRM method for the quantification of immunoglobulin subclasses and their site
      specific glycoforms, demonstrating that both quantities and glycoforms of
      immunoglobulins change significantly in liver disease progression to HCC.
      BIOLOGICAL SIGNIFICANCE: We have demonstrated that both quantities and glycoforms
      of immunoglobulin subclasses change significantly in liver disease progression to
      HCC through quantitative study of immunoglobulin subclasses and their site
      specific glycoforms using a sensitive and selective LC-MS-MRM method.
      Redistribution of the glycoforms of specific immunoglobulin subclasses could have
      important implications for receptor mediated responses affecting the progression
      of liver disease.

PMID- 25582526
TI  - Accuracy of portable devices in measuring peak cough flow.
AB  - Peak cough flow (PCF) measurements can be used as indicators of cough
      effectiveness. Portable peak flow meters and spirometers have been used to
      measure PCF, but little is known about their accuracy compared to
      pneumotachograph systems. The aim of this study was to compare the accuracy of
      four portable devices (Mini-Wright and Assess peak flow meters, SpiroUSB and
      Microlab spirometers) in measuring PCF with a calibrated laboratory based
      pneumotachograph system. Twenty healthy volunteers (mean (SD) age 45 (16) years)
      coughed through a pneumotachograph connected in series with each portable device
      in turn, and the differences in PCF readings were analysed. In addition,
      mechanically generated flow waves of constant peak flow were delivered through
      each device both independently and when connected in series with the
      pneumotachograph. Agreement between PCF readings obtained with the
      pneumotachograph and the portable devices was poor. Peak flow readings were on
      average lower by approximately 50 L min(-1) when measured using the portable
      devices; 95% limits of agreement spanned approximately 150 L min(-1). The
      findings highlight the potential for inaccuracy when using portable devices for
      the measurement of PCF. Depending on the measurement instrument used, absolute
      values of PCF reported in the literature may not be directly comparable.

PMID- 25582527
TI  - Anal cancer: current standards in care and recent changes in practice.
AB  - Answer questions and earn CME/CNE The management of squamous cell carcinomas of
      the anal canal has evolved from surgery as first-line treatment to curative
      chemoradiation, with surgery reserved for salvage. Significant progress has been
      made in understanding how to most effectively deliver chemotherapy and reduce
      toxicity through advancements in radiation delivery. The purpose of this article
      is to review the multimodality approach to the diagnosis and management of anal
      cancer based on a review of the published data and in light of available
      guidelines.

PMID- 25582528
TI  - Editorial comment for Pastore et al.

PMID- 25582523
TI  - Viral infections during pregnancy.
AB  - Viral infections during pregnancy have long been considered benign conditions
      with a few notable exceptions, such as herpes virus. The recent Ebola outbreak
      and other viral epidemics and pandemics show how pregnant women suffer worse
      outcomes (such as preterm labor and adverse fetal outcomes) than the general
      population and non-pregnant women. New knowledge about the ways the maternal
      fetal interface and placenta interact with the maternal immune system may explain
      these findings. Once thought to be 'immunosuppressed', the pregnant woman
      actually undergoes an immunological transformation, where the immune system is
      necessary to promote and support the pregnancy and growing fetus. When this
      protection is breached, as in a viral infection, this security is weakened and
      infection with other microorganisms can then propagate and lead to outcomes, such
      as preterm labor. In this manuscript, we review the major viral infections
      relevant to pregnancy and offer potential mechanisms for the associated adverse
      pregnancy outcomes.

PMID- 25582529
TI  - Radiology Teaching Files: an Assessment of Their Role and Desired Features Based
      on a National Survey.
AB  - A radiology teaching file (TF) is a system containing a collection of cases with
      teaching value. Given the wide variety of TF solutions available, we conducted a
      national survey to better understand the need for TFs, TF features desired by
      users and their current implementation. A 28-question survey was created which
      explored TF implementation, utilization, and preferences among respondents. The
      survey was emailed to residents and faculty throughout the USA, with a request
      for program coordinators to forward the survey to their departments. The survey
      was completed by 396 respondents from 115 different institutions. These
      respondents included 60% residents, 21% attendings (non-program directors), 12%
      program directors, 5% fellows, and 1% medical students. TFs were assigned to one
      of three categories: personal TFs, shared in-house TFs, and public TFs. Seventy
      six percent of respondents kept a personal TF using a variety of media, and 67%
      used a shared in-house TF. Of the public TFs used, the most popular were those
      requiring paid subscriptions. The features respondents valued most provided
      efficient querying of cases, simulated basic PACS functionality, enabled self
      directed learning, and facilitated case submissions. There is a trend toward
      utilizing electronic media for TFs. The media utilized should be understood and
      reviewed to ensure PHI is properly secured. Contemporary users demand a high
      degree of functionality from TF solutions, and use both in-house and commercial
      products to meet their needs.

PMID- 25582530
TI  - A Pilot Study on the Development of Remote Quality Control of Digital Mammography
      Systems in the NHS Breast Screening Programme.
AB  - In the UK, physicists and radiographers perform routine quality control (QC) of
      digital mammography equipment at daily, weekly and monthly intervals. The tests
      performed and tolerances are specified by standard protocols. The manual nature
      of many of the tests introduces variability due to the positioning of regions of
      interest (ROIs) and can be time consuming. The tools on workstations provided by
      manufacturers limit the range of analysis that radiographers can perform and do
      not allow for a standard set of tools and analysis because they are specific to a
      given manufacturer. Automated software provides a means of reducing the
      variability in the analysis and also provides the possibility of additional, more
      complex analysis than is currently performed on the daily, weekly and monthly
      checks by radiographers. To this end, a set of tools has been developed to
      analyse the routine images taken by radiographers. As well as automatically
      reproducing the usual measurements by radiographers more complex analysis is
      provided. A QC image collection system has been developed which automatically
      routes QC data from a clinical site to a centralised server for analysis. A Web
      based interface has been created that allows the users to view the performance of
      the mammographic equipment. The pilot system obtained over 3000 QC images from
      seven X-ray units at a single screening centre over 2 years. The results show
      that these tools and methods of analysis can highlight changes in a detector over
      time that may otherwise go unnoticed with the conventional analysis. 

PMID- 25582531
TI  - Changing dietary behaviour: the role and development of practitioner
      communication.
AB  - The need to support people to change diet-related behaviour is widely advocated
      and how to do this effectively in practice is an expanding area of research.
      Important factors to consider are how healthcare practitioners communicate with
      their patients and how that communication may affect diet-related behaviour
      change and subsequent outcomes. The aim of the present paper is to discuss
      communication skills for behaviour change (CSBC), focusing predominantly on
      registered dietitians who are required to communicate effectively and have an
      important role in supporting patients to change diet-related behaviour. The views
      of dietitians in relation to CSBC have been investigated and respondents have
      consistently reported that they perceive these skills to be of vital importance
      in practice. Patient views have reiterated the importance of good CSBC in one-to
      one consultations. However, pre-qualification training of dietitians is thought
      to deliver practitioners who are competent at a minimum level. The need for
      ongoing continuous professional development (CPD) in relation to CSBC has been
      recognised but currently most CPD focuses on updating knowledge rather than
      improving these essential skills. Measuring CSBC in a consistent and objective
      manner is difficult and an assessment tool, DIET-COMMS, has been developed and
      validated for this purpose. DIET-COMMS can be used to support CSBC development,
      but concerns about logistical challenges and acceptability of implementing this
      in practice have been raised. Although a suitable assessment tool now exists
      there is a need to develop ways to facilitate assessment of CSBC in practice. 

PMID- 25582533
TI  - WITHDRAWN: Experience with ustekinumab in patients with psoriasis enrolled in a
      large, multicenter, prospective, disease-based registry (Psoriasis Longitudinal
      Assessment and Registry [PSOLAR]).
AB  - The above-referenced article has been voluntarily withdrawn by the authors in
      order to present more updated data in a subsequent manuscript. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 25582532
TI  - Framing recommendations to promote prevention behaviors among people at high
      risk: A simulation study of responses to melanoma genetic test reporting.
AB  - A CDKN2A/p16 mutation confers 76 % lifetime risk of developing melanoma to US
      residents, and high-risk individuals are counseled to use sunscreen. Generally,
      for patients at population risk, gain framing more effectively promotes
      prevention behaviors; however, it is unknown whether loss frames might more
      effectively promote behavioral intentions and perceived control over disease risk
      among high-risk patients. Undergraduates (N = 146) underwent a simulated genetic
      counseling and test reporting session for hereditary melanoma. Participants
      watched a video of a genetic counselor providing information in which genetic
      risk of melanoma (Low: 15 %; High: 76 %) and framed recommendations to use
      sunscreen (Loss: Risk may increase by 15 % if don't use sunscreen; Gain: Risk may
      decrease by 15 % if use sunscreen) were manipulated. Controlling for baseline
      sunscreen use, high-risk participants given loss frames reported greater beliefs
      that sunscreen would reduce risk than high-risk participants given gain frames.
      Further, high-risk participants with fair skin tended to report greater
      intentions to use sunscreen when given loss frames versus gain frames. Perceived
      control over risk mediated the effect of message frame and disease risk on
      intentions to use sunscreen. When counseling patients with elevated cancer risk,
      genetic counselors may consider framing prevention behavioral recommendations in
      terms of potential losses.

PMID- 25582534
TI  - CD30(+) cutaneous lymphoproliferative disorders with pseudocarcinomatous
      hyperplasia are associated with a T-helper-17 cytokine profile and infiltrating
      granulocytes.
AB  - BACKGROUND: The pathogenetic mechanism of CD30(+) cutaneous lymphoproliferative
      disorders (CLPD) associated with pseudocarcinomatous hyperplasia (PCH) and
      granulocytic inflammation surrounding atypical CD30(+) lymphocytes remains
      unclear. OBJECTIVE: We sought to characterize clinical and pathological findings
      of a cohort of patients with PCH associated with CD30(+) CLPD and to analyze the
      cytokine profile of the atypical lymphocytes. METHODS: We retrospectively
      reviewed medical records and pathological material of CD30(+) CLPD with PCH.
      Immunohistochemistry for T-helper (Th)17 cytokine profile was performed. RESULTS:
      In all, 25 patients with a median age of 52 years were included. The median
      follow-up was 3.7 years. Histologically, an infiltrating pattern of PCH was
      observed in 14 cases with a neutrophilic-rich infiltrate (P = .21), and epidermal
      pattern in 11 cases with eosinophil-rich infiltrate (P = .03). Th17 or Th22
      cytokines were detected in tumor cells in 81% cases tested. Tumor cells expressed
      Th17 transcription factor retinoic acid receptor (ROR)-related orphan receptor
      gamma-2 in 2 of 7 samples tested and 1 was positive for aryl hydrocarbon
      receptor. LIMITATIONS: This is a retrospective study of a small sample.
      CONCLUSIONS: PCH in CD30(+) CLPD is associated with Th17/Th22 cytokine expression
      in the atypical lymphocytes. Although these lesions commonly regress
      spontaneously and are associated with an indolent course, some cases develop a
      generalized process and tumor progression.

PMID- 25582535
TI  - Viral infections in acute graft-versus-host disease: a review of diagnostic and
      therapeutic approaches.
AB  - BACKGROUND: While immunosuppressive therapy for acute graft-versus-host disease
      (aGVHD) advances, viral reactivation has been found to be an increasingly common
      complication in these patients. Dermatologists may often be consulted on
      inpatient services for evaluation. OBJECTIVE: We investigated the literature for
      the role of viral infections in aGVHD and review the current evidence regarding
      management. METHODS: Articles in the public domain regarding aGVHD,
      cytomegalovirus, Epstein-Barr virus, varicella zoster virus, hepatitis viruses,
      parvovirus B19, and respiratory viruses were included. RESULTS: Dermatologic
      findings vary between different viral antigens, and some infections may be a
      marker for the development of aGVHD or worsen prognosis. LIMITATIONS: The
      heterogeneous cohorts of the studies reviewed often preclude direct comparison
      between results. CONCLUSION: The relationship between viral reactivation and
      aGVHD may be bidirectional and is worthy of further exploration. Additional
      studies are needed to determine appropriate prophylaxis and treatment.

PMID- 25582536
TI  - Predictive value of biopsy specimens suspicious for melanoma: support for 6-mm
      criterion in the ABCD rule.
AB  - OBJECTIVE: Clinical detection of melanoma can be challenging. The number of
      biopsy specimens performed to diagnose 1 melanoma is a measure of efficiency of
      skin cancer detection, but few data are available to describe this measure from
      US health care. We studied the diagnosis of melanoma among biopsy specimens of
      clinically concerning pigmented lesions at an academic dermatology department.
      METHODS: We searched for all biopsy specimens that were performed because of
      clinical suspicion of melanoma in 2013. Characteristics of the patient, lesion,
      and clinician performing the biopsy, and the final pathology diagnosis were
      recorded. RESULTS: A total of 2643 biopsy specimens from 2213 patients submitted
      by 43 providers were included. Melanoma was diagnosed in 165 cases (positive
      predictive value 6.4%, 95% confidence interval 5.5%-7.4%). Older age (P < .001),
      male gender (P = .045), and nontrunk location (P < .001) were predictors of
      higher probability of melanoma detection. Lesions larger than 6 mm in size had
      higher positive predictive value 11.5% (8.8%-14.1%) than smaller lesions 2.6%
      (1.6%-3.6%). LIMITATIONS: Factors influencing the decision to biopsy a lesion may
      be difficult to evaluate retrospectively. CONCLUSION: At an academic medical
      center, 16 clinically concerning lesions were biopsied to diagnose 1 melanoma.
      Biopsy specimens of clinically concerning pigmented lesions larger than 6 mm on
      older men had the highest yield.

PMID- 25582537
TI  - Prognostic impact of fibrosarcomatous transformation in dermatofibrosarcoma
      protuberans: a cohort study.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade cutaneous
      malignancy that sometimes transforms into a high-grade fibrosarcomatous variant
      (DFSP-FS). Limited data compare clinical features and biological behavior of
      these 2 entities. OBJECTIVE: We sought to compare clinical features and
      biological behavior of DFSP and DFSP-FS. METHODS: This was a retrospective cohort
      study of ambulatory patients with DFSP or DFSP-FS treated between January 1955
      and March 2012 in the dermatology department of a tertiary care academic medical
      center. RESULTS: Of 188 patients, 171 (91%) had DFSP and 17 (9%) had DFSP-FS.
      Recurrence-free survival differed significantly between the groups over time (P =
      .002). The 1-year and 5-year recurrence-free survival was 94% and 86%,
      respectively, for DFSP, vs 86% and 42%, respectively, for DFSP-FS. Metastatic
      disease occurred in no patients with DFSP and in 18% (3 of 17) with DFSP-FS (P <
      .001). There were no statistically significant differences in age at diagnosis,
      sex, race, symptomatology, maximum tumor size, muscle/bone invasion, or duration
      of tumor before diagnosis. LIMITATIONS: The retrospective nature of study was a
      limitation. CONCLUSIONS: DFSP-FS exhibits more aggressive behavior than DFSP,
      with lower recurrence-free survival and greater metastatic potential. Their
      similar clinical presentation mandates histopathological differentiation for
      prognosis.

PMID- 25582538
TI  - Novel oral anticoagulants: what dermatologists need to know.
AB  - The development of novel oral anticoagulants provides clinicians and patients a
      welcome alternative to the challenges of warfarin therapy. Dermatologists must be
      aware of the potential impact of novel oral anticoagulants on their surgical and
      medical practice. This review provides a concise summary of the novel oral
      anticoagulants for dermatologists with particular emphasis on: (1) the
      pharmacokinetic properties of these drugs and how they differ from warfarin, (2)
      suggested management during cutaneous surgery, (3) adverse drug interactions with
      commonly prescribed medications in dermatology, and (4) potential use within
      dermatology for treatment of disorders of cutaneous thrombosis.

PMID- 25582539
TI  - Association of occupational exposure with features of systemic sclerosis.
AB  - BACKGROUND: Occupational exposure is reported as playing a substantial causative
      role in systemic sclerosis (SSc). OBJECTIVE: We sought to compare the
      characteristics of SSc in patients with and without occupational exposure to
      crystalline silica/solvents. METHODS: In all, 142 patients with SSc were enrolled
      in this prospective study. An expert committee performed blind evaluation of
      occupational exposure to crystalline silica/solvents. RESULTS: Patients exposed
      to crystalline silica more often exhibited: diffuse cutaneous SSc (P = .02),
      digital ulcers (P = .05), interstitial lung disease (P = .0004), myocardial
      dysfunction (P = .006), and cancer (P = .06). Patients exposed to solvents more
      frequently developed: diffuse cutaneous SSc (P = .001), digital ulcers (P = .01),
      interstitial lung disease (P = .02), myocardial dysfunction (P = .04), and cancer
      (P = .003); in addition, these patients were more frequently anti-Scl 70 positive
      and anticentromere negative. Under multivariate analysis, significant factors for
      SSc associated with exposure to silica/solvents were: male gender (odds ratio
      19.31, 95% confidence interval 15.34-69.86), cancer (odds ratio 5.97, 95%
      confidence interval 1.55-23.01), and digital ulcers (odds ratio 2.42, 95%
      confidence interval 1.05-5.56). LIMITATIONS: The cohort originated from a single
      geographic region. CONCLUSION: Occupational exposure to crystalline
      silica/solvents is correlated with more severe forms of SSc characterized by:
      diffuse cutaneous involvement, interstitial lung disease, general microangiopathy
      (digital ulcers and myocardial dysfunction), and association with cancer.
      Occupational exposure should be systematically checked in all patients with SSc,
      as exposed patients seem to develop more severe forms of SSc.

PMID- 25582540
TI  - Kaposi varicelliform eruption in patients with Darier disease: a 20-year
      retrospective study.
AB  - BACKGROUND: Kaposi varicelliform eruption (KVE), or herpes simplex virus (HSV)
      superinfection of pre-existing skin lesions, may complicate Darier disease.
      OBJECTIVE: We sought to compare the clinical features and outcomes of patients
      with Darier disease who developed KVE superinfection with those who did not.
      METHODS: A 20-year retrospective analysis of 79 patients with Darier disease
      treated at our institution was performed. RESULTS: Eleven (14%) patients
      developed KVE, of whom 45% required hospitalization for their skin disease during
      the follow-up period. Patients with KVE had more severe Darier disease (P = .030)
      and were more likely to be hospitalized (P = .015). HSV was detected in erosions
      without concomitant vesicles or pustules in 64% of confirmed cases. In all, 23
      (55%) patients with erosions had HSV testing pursued. LIMITATIONS: Retrospective
      study design is a limitation. CONCLUSION: The majority of KVE occurs in painless
      or painful erosions that may also appear impetiginized without vesicle or pustule
      formation. As HSV superinfection is correlated with severe Darier disease and
      risk for hospitalization, increased recognition of this phenomenon may lead to
      better patient outcomes.

PMID- 25582541
TI  - Correlation of early-onset hidradenitis suppurativa with stronger genetic
      susceptibility and more widespread involvement.
AB  - BACKGROUND: The reported mean age of onset of hidradenitis suppurativa (HS) is
      between 20 and 24 years. Prepubertal onset is thought to be rare. OBJECTIVE: We
      sought to determine the prevalence of early-onset HS and to compare clinical
      characteristics between early-onset and normal-onset HS in a retrospective study.
      METHODS: Data were collected from 855 patients with HS. Early-onset HS was
      defined as onset before the thirteenth birthday. Clinical characteristics were
      analyzed in relation to the age of onset. RESULTS: In all, 66 patients (7.7%)
      reported early-onset HS. A family history for HS was significantly higher in
      early-onset patients (55.6% vs 34.2%; odds ratio 2.1, 95% confidence interval 1.2
      3.6, P = .006). They developed inflammatory lesions at more body sites than
      patients with normal-onset HS (odds ratio 3.0, 95% confidence interval 1.8-4.9, P
      < .001). Distribution of the Hurley stages of severity showed no differences
      between the 2 groups (odds ratio 1.1, 95% confidence interval 0.7-1.8, P = .72).
      LIMITATIONS: Some data were based on patient-reported information. CONCLUSION:
      Early-onset HS occurs more frequently than previously believed. Patients with
      early-onset HS often report a family history for HS and develop lesions at more
      body sites.

PMID- 25582542
TI  - Predictors of response in initial users of metformin and sulphonylurea
      derivatives: a systematic review.
AB  - AIM: To provide an overview of factors predicting metformin and sulphonylurea
      treatment response. BACKGROUND: A large variability between individuals in
      treatment response to metformin and sulphonylurea derivatives exists.
      Understanding which factors determine response to these drugs may pave the way
      for more individualized therapy. METHODS: We conducted a systematic search in the
      MEDLINE, Cochrane and EMBASE databases, between 2003 and 2012 for articles
      assessing demographic and clinical prediction factors of treatment response in
      initial users of metformin or sulphonylurea. A literature search of articles
      referenced within the studies identified was also performed. Treatment response
      was defined as change in HbA1c level, reaching target HbA1c levels or time to
      treatment change. Studies were assessed on quality, sample size and type of
      analysis. Results were summarized by tabulating positive, null and negative
      associations observed for included predictors. RESULTS: A total of 10 articles
      (six trial reports and four cohort studies) were obtained, including three of
      sufficient quality. For metformin, baseline HbA1c , older age, lower BMI and
      shorter disease duration were found to be predictors of better treatment response
      in at least three studies of sufficient quality. For sulphonylurea derivatives,
      baseline HbA1c and shorter duration were identified as predictors of better
      treatment response in at least two studies of sufficient quality. Race, smoking
      status, lipid levels, blood pressure, kidney function and comorbidities were not
      significantly associated with treatment response. CONCLUSIONS: Several
      demographic and clinical factors were identified as possible predictors of
      response to metformin and sulphonylurea, but the number of studies with
      sufficient quality was small. Generally, early treatment seems important for
      achieving better glycaemic outcomes.

PMID- 25582543
TI  - Reversible brain swelling in crucian carp (Carassius carassius) and goldfish
      (Carassius auratus) in response to high external ammonia and anoxia.
AB  - Increased internal ammonia (hyperammonemia) and ischemic/anoxic insults are known
      to result in a cascade of deleterious events that can culminate in potentially
      fatal brain swelling in mammals. It is less clear, however, if the brains of
      fishes respond to ammonia in a similar manner. The present study demonstrated
      that the crucian carp (Carassius carassius) was not only able to endure high
      environmental ammonia exposure (HEA; 2 to 22 mmol L(-1)) but that they
      experienced 30% increases in brain water content at the highest ammonia
      concentrations. This swelling was accompanied by 4-fold increases in plasma total
      ammonia (TAmm) concentration, but both plasma TAmm and brain water content were
      restored to pre-exposure levels following depuration in ammonia-free water. The
      closely related, ammonia-tolerant goldfish (Carassius auratus) responded
      similarly to HEA (up to 3.6 mmol L(-1)), which was accompanied by 4-fold
      increases in brain glutamine. Subsequent administration of the glutamine
      synthetase inhibitor, methionine sulfoximine (MSO), reduced brain glutamine
      accumulation by 80% during HEA. However, MSO failed to prevent ammonia-induced
      increases in brain water content suggesting that glutamine may not be directly
      involved in initiating ammonia-induced brain swelling in fishes. Although the
      mechanisms of brain swelling are likely different, exposure to anoxia for 96 h
      caused similar, but lesser (10%) increases in brain water content in crucian
      carp. We conclude that brain swelling in some fishes may be a common response to
      increased internal ammonia or lower oxygen but further research is needed to
      deduce the underlying mechanisms behind such responses.

PMID- 25582544
TI  - Physiological, cellular and biochemical thermal stress response of intertidal
      shrimps with different vertical distributions: Palaemon elegans and Palaemon
      serratus.
AB  - The ability to cope with high temperature variations is a critical factor in
      intertidal communities. Two species of intertidal rocky shore shrimps (Palaemon
      sp.) with different vertical distributions were collected from the Portuguese
      coast in order to test if they were differentially sensitive to thermal stress.
      Three distinct levels of biological organization (organismal, biochemical, and
      cellular) were surveyed. The shrimp were exposed to a constant rate of
      temperature increase of 1 degrees C x h(-1), starting at 20 degrees C until
      reaching the CTMax (critical thermal maximum). During heat stress, two biomarkers
      of protein damage were quantified in the muscle via enzyme-linked immunosorbent
      assays: heat shock proteins HSP70 (hsp70/hsc70) and total ubiquitin. Muscle
      histopathological alterations caused by temperature were also evaluated. CTMax
      values were not significantly different between the congeners (P. elegans 33.4 +/
      0.5  degrees C; P. serratus 33.0 +/- 0.5  degrees C). Biomarker levels did not
      increase along the temperature trial, but P. elegans (higher intertidal) showed
      higher amounts of HSP70 and total ubiquitin than P. serratus (lower intertidal).
      HSP70 and total ubiquitin levels showed a positive significant correlation in
      both species, suggesting that their association is important in thermal
      tolerance. Histopathological observations of muscle tissue in P. serratus showed
      no gross alterations due to temperature but did show localized atrophy of muscle
      fibers at CTMax. In P. elegans, alterations occurred at a larger scale, showing
      multiple foci of atrophic muscular fascicles caused by necrotic or autolytic
      processes. In conclusion, Palaemon congeners displayed different responses to
      stress at a cellular level, with P. elegans having greater biomarker levels and
      histopathological alterations.

PMID- 25582545
TI  - Shrinking Lung in Primary Sjogren Syndrome Successfully Treated with Rituximab.

PMID- 25582546
TI  - Fast pyrolysis biochar from sawdust improves the quality of desert soils and
      enhances plant growth.
AB  - BACKGROUND: Biochar has been mostly used in conventional arable soils for
      improving soil fertility. This study investigated the effect of biochars of
      different temperatures on plant growth and desert soil properties. Biochars of
      different temperatures (i.e. 400, 500, 600, 700, and 800  degrees C) were mixed
      in the soil with 5% by mass, and the treatments were designated as T-400, T-500,
      T-600, T-700 and T-800, respectively. Sorghum was used as a test crop, and the
      effect of biochar on plant height, yield and soil properties was evaluated.
      RESULTS: Sorghum yield increased by 19% and 32% under T-400 and T-700,
      respectively, above the control. Biochar reduced depth-wise moisture depletion in
      soil columns and hence improved soil water-holding capacity by 14% and 57% under
      T-400 and T-700, respectively. Soil hydraulic conductivity was reduced by 15% and
      42%, and moisture-retention capacity was improved by 16% and 59%. Hence, sorghum
      net water-use efficiency increased by 52% and 74% in T-400 and T-700,
      respectively. Biochar also improved soil total carbon, cation exchange capacity
      and plant nutrient content. CONCLUSION: The addition of fast pyrolysis biochar
      made from pine sawdust improved the quality of Kubuqi Desert soil and enhanced
      plant growth. Hence, it can be used for desert modification.

PMID- 25582548
TI  - An examination of eating behaviors, physical activity, and obesity in african
      american adolescents: gender, socioeconomic status, and residential status
      differences.
AB  - BACKGROUND: African American adolescents experience higher rates of obesity and
      have an increased risk of obesity-related diseases than do White American
      adolescents. Despite culturally sensitive obesity preventive interventions,
      obesity rates are increasing within the African American adolescent population.
      Current obesity interventions do not usually address the heterogeneity (e.g.,
      socioeconomic status [SES], gender, and residential status differences) within
      the African American adolescent community that can affect the efficacy of these
      interventions. PURPOSE: To examine the gender, SES, and residential status
      differences related to obesity and weight behaviors in African American
      adolescents. METHODS: A descriptive correlational study was conducted with 15- to
      17-year-old African American adolescents (n = 145) from community clinics, youth
      organizations, churches, and social networks in metropolitan and inner-city
      Detroit. Data were collected through use of survey methods and analyzed with use
      of descriptive statistics, independent sample t tests, and multiple regression
      equations. RESULTS: Female adolescents consumed foods higher in fat and calories
      (t = -2.36, p = .019) and had more body fat (t = -9.37, p = .000) than did males.
      Adolescents of lower SES consumed food higher in fat and calories (t = -2.23, p =
      .027) and had higher body mass (t = -2.57, p = .011) than did adolescents of
      higher SES. Inner-city African American adolescents had higher levels of physical
      activity (t = -2.39, p = .018) and higher body mass (t = 2.24, p = .027) than did
      suburban African American adolescent counterparts. Gender, SES, and residential
      status were statistically significant predictors of eating behaviors, physical
      activity, body mass index, and body fat. CONCLUSIONS: The initial findings from
      the study will assist in better understanding the obesity epidemic that affects
      African American adolescents in disparate proportions. IMPLICATIONS: Further
      examination of the study variables is essential to serve as a basis for
      developmentally appropriate and culturally relevant targeted interventions with
      this population. Health care providers and obesity researchers who work with
      youth can use the initial findings from this study to advocate for healthy
      lifestyles while reducing the obesity disparity within the African American
      adolescent population.

PMID- 25582547
TI  - Higher blood aldosterone level in metabolic syndrome is independently related to
      adiposity and fasting plasma glucose.
AB  - BACKGROUND: Hypoadiponectinemia is a well-known state associated with metabolic
      syndrome (MetS) and insulin resistance (IR). Recently aldosterone has been highly
      associated with high blood pressure, and may thus be a possible biomarker for
      MetS and IR. In this study, we investigate the association of aldosterone with
      MetS and IR, and compare it with that of adiponectin. METHODS: In this cross
      sectional study, we recruited 556 women receiving physical examinations at a
      general hospital in central Taiwan. At the time of examination, we collected data
      on various demographic and physical characteristics and measured blood levels of
      aldosterone, adiponectin and a variety of metabolic factors. Multiple linear
      regression analysis was performed using adiponectin or aldosterone as the
      dependent variables. RESULTS: We found an inverse correlation between blood
      adiponectin and aldosterone (gamma = -0.11, P = 0.009). Adiponectin levels were
      lower and aldosterone levels higher in women with MetS that those without (8.1 +/
      0.4 vs. 11.5 +/- 0.2 MUg/mL, P < 0.001 and 691 +/- 50 vs. 560 +/- 11 pmol/L, P =
      0.013, respectively), as they were in women with and without IR (adiponectin 10.4
      +/- 0.5 vs. 11.3 +/- 0.2 MUg/mL, P = 0.003 and aldosterone 635 +/- 31 vs. 560 +/-
      11 pmol/L, P = 0.022). Although aldosterone was significantly related to body fat
      %, fasting plasma glucose and serum creatinine levels, the relationship between
      adiponectin and aldosterone was not obvious after adjustment in the multivariate
      analysis. CONCLUSION: Although aldosterone was related to metabolic factors,
      including body fat % and fasting plasma glucose in our female subjects, the
      relationship between aldosterone and adiponectin remains unclear.

PMID- 25582549
TI  - A practice of caution: spontaneous action potentials or artifactual spikes?
AB  - BACKGROUND: High density surface electromyogram (EMG) techniques with electrode
      arrays have been used to record spontaneous muscle activity, which is important,
      both for supporting the diagnosis of neuromuscular diseases and for laboratory
      based neurophysiological investigations. This short report addresses a practical
      issue we have experienced during recording of spontaneous muscle activity using
      electrode arrays from subjects with major neuromuscular disorders. FINDINGS: We
      show that recording artifacts can appear similar to spontaneous action potential
      spikes. Moreover, a causal filter may induce asymmetric distortions of an
      artifact and thus confuse it with a real action potential spike. As a
      consequence, for a single channel surface EMG recording, it might be difficult to
      judge whether a voltage transient is a real action potential or an artifact.
      Further investigation of the signal distributions among other channels of the
      array can be used to reach a more confident judgment. CONCLUSIONS: During
      examination of spontaneous muscle activity using electrode arrays, caution is
      required for differentiation of physiological signals from artifactual spikes,
      which is important for accurate extraction of diagnostic or investigatory
      information.

PMID- 25582551
TI  - [Wiedemann-Beckwith syndrome: a new approach for reduction glossoplasty using
      Ultracision((r))].
AB  - INTRODUCTION: A reduction glossectomy may be complicated by tongue and mouth
      floor edema and extend the recovery time for a normal tongue function. We
      performed reduction glossectomy using Ultracision((r)), an ultrasonic vibrating
      device, so as to limit these complications. TECHNICAL NOTE: We performed a
      keyhole glossoplasty under general anesthesia. The initial tongue incision was
      performed with a cold scalpel, then the glossectomy was continued with
      Ultracision((r)) only. We also used CURVED SHEARS((r)). We evaluated our
      preliminary results with 3 patients presenting with Wiedemann-Beckwith syndrome.
      CONCLUSION: Ultracision((r)) is a useful tool for intra-oral surgery, and should
      soon be more frequently used. It is an alternative to electrocautery for this
      type of surgery.

PMID- 25582550
TI  - The neuroprotective effect of salubrinal in a mouse model of traumatic brain
      injury.
AB  - We have previously reported that mild traumatic brain injury (mTBI) induced
      cognitive deficits as well as apoptotic changes in the brains of mice. Apoptosis
      may be caused by severe, prolonged accumulation of misfolded proteins, and
      protein aggregation in the endoplasmic reticulum (ER stress). In an additional
      study, we have reported that mTBI activated the pro-apoptotic arm of the
      integrated stress response (ISR). The main goal of the present study was to test
      the involvement of the adaptive eIF2alpha/ATF4 pathway in mTBI-affected brains.
      Head injury was induced with a noninvasive, closed-head weight drop (30 g) to ICR
      mice. Salubrinal, the selective phosphatase inhibitor of p-eIF2alpha, was
      injected immediately and 24 h after mTBI (1 mg/kg, ip). Y-maze and novel object
      recognition tests to assess spatial and visual memories, respectively, were
      conducted either 7 or 30 days post-trauma. Salubrinal administration
      significantly improved memory deficits following mTBI. Slaubrinal also prevented
      the elevation of degenerating neurons and the reduction of mature neurons in the
      cortex (as seen by immunofluorescent staining with Fluoro-Jade-B and NeuN
      antibodies, 72 h and 1 week post-mTBI, respectively). Western blot analysis
      revealed that salubrinal prevented the significant reduction in eIF2alpha and
      ATF4 phosphorylation in mTBI brains 72 h post-injury. Immunofluorescence staining
      revealed that although the reduction in p-eIF2alpha did not reach significance,
      salubrinal administration elevated it dramatically. Our results show that
      targeting the translational/adaptive arm of the ISR with salubrinal may serve as
      a therapeutic strategy for brain damage. 

PMID- 25582552
TI  - Tailored synthesis of photoactive TiO 2 nanofibers and Au/TiO 2 nanofiber
      composites: structure and reactivity optimization for water treatment
      applications.
AB  - Titanium dioxide (TiO2) nanofibers with tailored structure and composition were
      synthesized by electrospinning to optimize photocatalytic treatment efficiency.
      Nanofibers of controlled diameter (30-210 nm), crystal structure (anatase,
      rutile, mixed phases), and grain size (20-50 nm) were developed along with
      composite nanofibers with either surface-deposited or bulk-integrated Au
      nanoparticle cocatalysts. Their reactivity was then examined in batch suspensions
      toward model (phenol) and emerging (pharmaceuticals, personal care products)
      pollutants across various water qualities. Optimized TiO2 nanofibers meet or
      exceed the performance of traditional nanoparticulate photocatalysts (e.g.,
      Aeroxide P25) with the greatest reactivity enhancements arising from (i)
      decreasing diameter (i.e., increasing surface area), (ii) mixed phase composition
      [74/26 (+/-0.5) % anatase/rutile], and (iii) small amounts (1.5 wt %) of surface
      deposited, more so than bulk-integrated, Au nanoparticles. Surface Au deposition
      consistently enhanced photoactivity by 5- to 10-fold across our micropollutant
      suite independent of their solution concentration, behavior that we attribute to
      higher photocatalytic efficiency from improved charge separation. However, the
      practical value of Au/TiO2 nanofibers was limited by their greater degree of
      inhibition by solution-phase radical scavengers and higher rate of reactivity
      loss from surface fouling in nonidealized matrixes (e.g., partially treated
      surface water). Ultimately, unmodified TiO2 nanofibers appear most promising for
      use as reactive filtration materials because their performance was less
      influenced by water quality, although future efforts must increase the strength
      of TiO2 nanofiber mats to realize such applications. 

PMID- 25582554
TI  - Endoscopic submucosal dissection in gastric lesions: the 100 cases experience
      from a tertiary reference center in West.
AB  - OBJECTIVE: Endoscopic submucosal dissection (ESD) is an endoscopic treatment
      method widely used in premalignant and malignant lesions in countries of the Far
      East. This method, which is difficult technically and has a high complication
      risk rate, has rarely been performed in the West, because of the fewer number of
      upper gastrointestinal lesions. In the present study, we aimed to present our
      results of gastric ESD procedures in respect to the learning curve. METHODS: A
      total of 100 ESD procedures, which were performed in the stomach between April
      2012 and September 2014, were recorded prospectively before and after the
      procedure. Patient data were analyzed retrospectively. ESD procedures were
      numbered chronologically; the first 30 patients constituted group 1, whereas the
      rest were classified as the group 2. ESD results were compared between the
      groups. RESULTS: In a total of 95 patients, 100 gastric ESDs were performed. The
      overall en-bloc and complete resection rates were 93% and 92%, respectively. In
      respect of the learning curve, there were significant differences in the sizes of
      lesions and tissues obtained, procedure duration and dissection rate, snare use
      and knife preferences between groups (p = 0.002, p < 0.001, p = 0.003, p < 0.001,
      p = 0.009, and p < 0.001, respectively). No significant difference was detected
      in the en-bloc and complete resection rates and complications between the groups.
      CONCLUSION: According to guideline recommendations and masters for ESD, if ESD
      training is initiated and continued, successful ESD may be performed in localized
      lesions in the stomach.

PMID- 25582555
TI  - Internally oxidized Nb3Sn strands with fine grain size and high critical current
      density.
AB  - Nb3Sn strands fabricated using Nb-Zr alloy can be internally oxidized, provided
      that oxygen is properly supplied via an oxide powder. This allows the formation
      of fine intragranular and intergranular ZrO2 particles in a Nb3Sn matrix. These
      particles can refine the grain size by a factor of three and thereby greatly
      enhance the Nb3Sn critical current density.

PMID- 25582553
TI  - Comparison of the cardioprotective and renoprotective effects of the L/N-type
      calcium channel blocker, cilnidipine, in adriamycin-treated spontaneously
      hypertensive rats.
AB  - Cilnidipine is an L/N-type calcium channel blocker (CCB). The effects of
      cilnidipine on N-type channels give it unique organ-protective properties via the
      suppression of hyperactivity in the sympathetic nervous system (SNS) and renin
      angiotensin-aldosterone system (RAAS). In the present study, we compared the
      effects of cilnidipine and amlodipine (an L-type CCB) on cardiac and renal
      functions in spontaneously-hypertensive rats injected with adriamycin (ADR).
      After the weekly administration of ADR for 3 weeks, spontaneously-hypertensive
      rats were orally administered cilnidipine (20 mg/kg per day), amlodipine (3 mg/kg
      per day), or vehicle once daily for 4 weeks. A control group received saline
      rather than ADR, followed by vehicle for 4 weeks. Cilnidipine and amlodipine
      produced similar reductions in blood pressure after 4 weeks. Cilnidipine
      ameliorated ADR-induced heart and kidney damage, whereas amlodipine slightly
      improved cardiac echocardiographic parameters, but did not protect against ADR
      induced renal damage. Cilnidipine (but not amlodipine) suppressed the reflex SNS
      and RAAS hyperactivity caused by their antihypertensive effects. Furthermore,
      cilnidipine and amlodipine treatment decreased the urinary levels of
      adrenocortical hormones. The protective effects of cilnidipine against ADR
      induced renal and cardiac dysfunction might be associated with its blockade of N
      type calcium channels, in addition to its pleiotropic actions, which include the
      inhibition of the RAAS.

PMID- 25582556
TI  - Necrotizing fasciitis and infective endocarditis caused by Escherichia coli in a
      hemodialysis patient.
AB  - Patients with uremia are often immunocompromised and uremia patients undergoing
      maintenance dialysis are often vulnerable to uncommon infections. We report a 40
      year-old man who was undergoing maintenance hemodialysis and was initially
      diagnosed with monomicrobal necrotizing fasciitis of the lower limbs, based on
      blood and pus cultures that yielded Escherichia coli. His condition improved
      after surgical debridement and antibiotic therapy. However, he eventually died of
      intracranial hemorrhage related to septic emboli. Concurrent infective
      endocarditis was diagnosed based on an echocardiogram that indicated vegetation
      in the left ventricular region. Escherichia coli-related necrotizing fasciitis
      and infective endocarditis is rarely seen in clinical practice. There should be a
      high index of suspicion for multiple infections when a hemodialysis patient
      presents with an uncommon infection. 

PMID- 25582557
TI  - Synthesis of large and few atomic layers of hexagonal boron nitride on melted
      copper.
AB  - Hexagonal boron nitride nanosheets (h-BNNS) have been proposed as an ideal
      substrate for graphene-based electronic devices, but the synthesis of large and
      homogeneous h-BNNS is still challenging. In this contribution, we report a facile
      synthesis of few-layer h-BNNS on melted copper via an atmospheric pressure
      chemical vapor deposition process. Comparative studies confirm the advantage of
      using melted copper over solid copper as a catalyst substrate. The former leads
      to the formation of single crystalline h-BNNS that is several microns in size and
      mostly in mono- and bi-layer forms, in contrast to the polycrystalline and mixed
      multiple layers (1-10) yielded by the latter. This difference is likely to be due
      to the significantly reduced and uniformly distributed nucleation sites on the
      smooth melted surface, in contrast to the large amounts of unevenly distributed
      nucleation sites that are associated with grain boundaries and other defects on
      the solid surface. This synthesis is expected to contribute to the development of
      large-scale manufacturing of h-BNNS/graphene-based electronics. 

PMID- 25582559
TI  - Transcriptional analysis of adaptation to high glucose concentrations in
      Zymomonas mobilis.
AB  - The ethanologenic bacterium Zymomonas mobilis is usually tolerant to high
      concentrations of glucose. The addition of sorbitol decreases the lag phase and
      increases ethanol yield and productivity of the bacteria in high glucose
      concentrations. The molecular mechanisms of adaptation to high glucose
      concentrations and the effect of sorbitol are still unclear. In this study,
      microarray analysis was used to study the global transcriptional adaptation
      responses of Z. mobilis to high glucose concentrations. A total of 235 genes were
      differentially expressed when 220 g/L glucose was added with or without 10 mM
      sorbitol. These genes are involved in diverse aspects of cell metabolism and
      regulation, including membrane transporters, nitrogen metabolism, and plasmid
      encoded genes. However, most differentially expressed genes were downregulated
      when sorbitol was added. Notably, the transcription of almost all genes involved
      in the Entner-Doudoroff and ethanol production pathways was not significantly
      affected. In addition, a prophage and a nitrogen-fixation cluster were
      significantly induced. These results revealed that Z. mobilis cells responded to
      high glucose concentrations by regulating the transcriptional levels of genes
      related to membrane channels and transporters, stress response mechanisms, and
      metabolic pathways. These data provide insight into the intracellular adaptation
      responses to high glucose concentrations and reveal strategies to engineer
      efficient ethanol fermentation in Z. mobilis. 

PMID- 25582558
TI  - The impact of oxygen on the final alcohol content of wine fermented by a mixed
      starter culture.
AB  - We have developed a wine fermentation procedure that takes advantage of the
      metabolic features of a previously characterized Metschnikowia pulcherrima strain
      in order to reduce ethanol production. It involves the use of M.
      pulcherrima/Saccharomyces cerevisiae mixed cultures, controlled oxygenation
      conditions during the first 48 h of fermentation, and anaerobic conditions
      thereafter. The influence of different oxygenation regimes and initial inoculum
      composition on yeast physiology and final ethanol content was studied. The impact
      of oxygenation on yeast physiology goes beyond the first aerated step and
      influences yields and survival rates during the anaerobic stage. The activity of
      M. pulcherrima in mixed oxygenated cultures resulted in a clear reduction in
      ethanol yield, as compared to S. cerevisiae. Despite relatively low initial cell
      numbers, S. cerevisiae always predominated in mixed cultures by the end of the
      fermentation process. Strain replacement was faster under low oxygenation levels.
      M. pulcherrima confers an additional advantage in terms of dissolved oxygen,
      which drops to zero after a few hours of culture, even under highly aerated
      conditions, and this holds true for mixed cultures. Alcohol reduction values
      about 3.7 % (v/v) were obtained for mixed cultures under high aeration, but they
      were associated to unacceptable volatile acidity levels. In contrast, under
      optimized conditions, only 0.35 g/L acetic acid was produced, for an alcohol
      reduction of 2.2 % (v/v), and almost null dissolved oxygen during the process.

PMID- 25582560
TI  - Correlation of nitric oxide produced by an inducible nitric oxide synthase-like
      protein with enhanced expression of the phenylpropanoid pathway in Inonotus
      obliquus cocultured with Phellinus morii.
AB  - Fungal interspecific interactions enhance biosynthesis of phenylpropanoid
      metabolites (PM), and production of nitric oxide (NO) is known to be involved in
      this process. However, it remains unknown which signaling pathway(s) or
      regulator(s) mediate fungal PM biosynthesis. In this study, we cocultured two
      white-rot fungi, Inonotus obliquus and Phellinus morii, to examine NO production,
      expression of the genes involved in phenylpropanoid metabolism and accumulation
      of phenylpropanoid-derived polyphenols by I. obliquus. Coculture of the two fungi
      caused an enhanced NO biosynthesis followed by increased transcription of the
      genes encoding phenylalanine ammonia lyase (PAL) and 4-coumarate CoA ligase
      (4CL), as well as an upregulated biosynthesis of styrylpyrone polyphenols in I.
      obliquus. Addition of the NO synthase (NOS) selective inhibitor aminoguanidine
      (AG) inhibited NO production by more than 90% followed by cease in transcription
      of PAL and 4Cl. Treatment of guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one did not affect NO production but suppressed transcription of
      PAL and 4CL and reduced accumulation of total phenolic constituents. Genome-wide
      analysis of I. obliquus revealed two genes encoding a constitutive and an
      inducible NOS-like protein, respectively (cNOSL and iNOSL). Coculture of the two
      fungi did not increase the expression of the cNOSL gene but triggered expression
      of the iNOSL gene. Cloned iNOSL from Escherichia coli shows higher activity in
      transferring L-arginine to NO, and this activity is lost upon AG addition. Thus,
      iNOSL is more responsible for NO production in I. obliquus and may act as an
      important regulator governing PM production during fungal interspecific
      interactions.

PMID- 25582561
TI  - Enzyme multilayer coatings inhibit Pseudomonas aeruginosa biofilm formation on
      urinary catheters.
AB  - Bacteria use a signaling mechanism called quorum sensing (QS) to form complex
      communities of surface-attached cells known as biofilms. This protective mode of
      growth allows them to resist antibiotic treatment and originates the majority of
      hospital-acquired infections. Emerging alternatives to control biofilm-associated
      infections and multidrug resistance development interfere with bacterial QS
      pathways, exerting less selective pressure on bacterial population. In this
      study, biologically stable coatings comprising the QS disrupting enzyme acylase
      were built on silicone urinary catheters using a layer-by-layer technique. This
      was achieved by the alternate deposition of negatively charged enzyme and
      positively charged polyethylenimine. The acylase-coated catheters efficiently
      quenched the QS in the biosensor strain Chromobacterium violaceum CECT 5999,
      demonstrated by approximately 50% inhibition of violacein production. These
      enzyme multilayer coatings significantly reduced the Pseudomonas aeruginosa ATCC
      10145 biofilm formation under static and dynamic conditions in an in vitro
      catheterized bladder model. The quorum quenching enzyme coatings did not affect
      the viability of the human fibroblasts (BJ-5ta) over 7 days, corresponding to the
      extended useful life of urinary catheters. Such enzyme-based approach could be an
      alternative to the conventional antibiotic treatment for prevention of biofilm
      associated urinary tract infections.

PMID- 25582562
TI  - The evolution of sex chromosomes in organisms with separate haploid sexes.
AB  - The evolution of dimorphic sex chromosomes is driven largely by the evolution of
      reduced recombination and the subsequent accumulation of deleterious mutations.
      Although these processes are increasingly well understood in diploid organisms,
      the evolution of dimorphic sex chromosomes in haploid organisms (U/V) has been
      virtually unstudied theoretically. We analyze a model to investigate the
      evolution of linkage between fitness loci and the sex-determining region in U/V
      species. In a second step, we test how prone nonrecombining regions are to
      degeneration due to accumulation of deleterious mutations. Our modeling predicts
      that the decay of recombination on the sex chromosomes and the addition of strata
      via fusions will be just as much a part of the evolution of haploid sex
      chromosomes as in diploid sex chromosome systems. Reduced recombination is
      broadly favored, as long as there is some fitness difference between haploid
      males and females. The degeneration of the sex-determining region due to the
      accumulation of deleterious mutations is expected to be slower in haploid
      organisms because of the absence of masking. Nevertheless, balancing selection
      often drives greater differentiation between the U/V sex chromosomes than in X/Y
      and Z/W systems. We summarize empirical evidence for haploid sex chromosome
      evolution and discuss our predictions in light of these findings. 

PMID- 25582563
TI  - The effects of exercise training programs on plasma concentrations of
      proenkephalin Peptide F and catecholamines.
AB  - To determine if exercise training alters the pattern and magnitude of plasma
      concentrations of proenkephalin Peptide F and epinephrine, plasma proenkephalin
      [107-140] Peptide F(ir) and catecholamines were examined pre-training (T-1), and
      after 4- (T-2), 8- (T-3), and 12-weeks (T-4) of training. 26 healthy men were
      matched and randomly assigned to one of three groups: heavy resistance strength
      training (Strength, n=9), high intensity endurance training (Endurance, n=8), or
      both training modalities combined (Combined, n=9). Blood was collected using a
      syringe with a cannula inserted into a superficial arm vein with samples
      collected at rest, after each 7 min stage and 5 and 15 min into recovery. With
      training, all groups observed shifted plasma Peptide F responses to graded
      exercise, where significant increases were observed at lower exercise
      intensities. Increases in plasma epinephrine with exercise were observed in all
      groups. The Combined group saw increases at 25% at T-3 and for 50% at T-2, T-3,
      and T-4 which was higher than T-1. The Endurance group demonstrated increases for
      50% at T-1, T-2, T-3 but not at T-4. The plasma epinephrine response to graded
      exercise was reduced in the Strength group. Increases in plasma norepinephrine
      above rest were observed starting at 50% . The Strength group demonstrated a
      significant reduction in norepinephrine observed at 100% at T-3 and T-4. Peptide
      F and catecholamines responses to graded exercise can be altered by different
      types of physical exercise training. Simultaneous high intensity training may
      produce adrenal medulla exhaustion when compared to single mode training.

PMID- 25582565
TI  - Role of in vivo dosimetry with radiochromic films for dose verification during
      cutaneous radiation therapy.
AB  - PURPOSE: To evaluate the role of in vivo dosimetry with radiochromic films for
      dose verification in cutaneous radiation therapy (RT). METHODS: Five patients
      with 8 cutaneous or sub-cutaneous malignancies of the face, neck, trunk and
      extremity receiving RT were included. Orthovoltage, megavoltage photon therapies
      were applied based on anatomic location. The delivered dose for each target was
      measured with GAFCHROMIC EBT3TM film. The differences between the prescribed and
      measured doses in each target were analyzed based on the RT characteristics,
      target location and custom patient set up. The accuracy of EBT3TM film
      measurement was verified by measurements in a solid water phantom. RESULTS: The
      mean measured dose was -3.2% (-9.6% to +2.3%, P=0.86) lower than prescribed over
      23 measurements. A wide range of under dose was detected in orthovoltage therapy
      when a gap existed between skin and a closed-ended applicator surface. The
      magnitude of the under dosage was correlated with the degree of the gap (P=0.01).
      The phantom study confirmed the accuracy of GAFCHROMIC EBT3TM film measurement
      and found that the low measured dose in orthovoltage therapy was caused by the
      deviation from the inverse square law (ISL) of the beam output at extended source
      surface distance (SSD) for closed-ended applicators. CONCLUSIONS: A significantly
      low delivered dose for extended SSD orthovoltage therapy was demonstrated during
      cutaneous RT. The dose fall-off with distance is not completely compensated by
      the ISL standoff correction for orthovoltage therapy. GAFCHROMIC EBT3TM film is a
      useful and accurate tool for quality assurance of patients receiving a curative
      intended cutaneous RT.

PMID- 25582567
TI  - Powder X-ray diffraction, infrared and (13)C NMR spectroscopic studies of the
      homologous series of some solid-state zinc(II) and sodium(I) n-alkanoates.
AB  - A comparative study of the room temperature molecular packing and lattice
      structures for the homologous series of zinc(II) and sodium(I) n-alkanoates
      adduced from Fourier transform infrared and solid-state (13)C NMR spectroscopic
      data in conjunction with X-ray powder diffraction measurements is carried out.
      For zinc carboxylates, metal-carboxyl bonding is via asymmetric bridging
      bidentate coordination whilst for the sodium adducts, coordination is via
      asymmetric chelating bidentate bonding. All compounds are packed in a monoclinic
      crystal system. Furthermore, the fully extended all-trans hydrocarbon chains are
      arranged as lamellar bilayers. For zinc compounds, there is bilayer overlap, for
      long chain adducts (nc>8) but not for sodium compounds where methyl groups from
      opposing layers in the lamellar are only closely packed. Additionally, the
      hydrocarbon chains are extended along the a-axis of the unit cell for zinc
      compounds whilst for sodium carboxylates they are extended along the c-axis.
      These packing differences are responsible for different levels of Van der Waals
      effects in the lattices of these two series of compounds, hence, observed odd
      even alternation is different. The significant difference in lattice packing
      observed for these two series of compounds is proposed to be due to the
      difference in metal-carboxyl coordination mode, arising from the different
      electronic structure of the central metal ions. 

PMID- 25582564
TI  - Electrical stimulation for the treatment of lower urinary tract dysfunction after
      spinal cord injury.
AB  - Electrical stimulation for bladder control is an alternative to traditional
      methods of treating neurogenic lower urinary tract dysfunction (NLUTD) resulting
      from spinal cord injury (SCI). In this review, we systematically discuss the
      neurophysiology of bladder dysfunction following SCI and the applications of
      electrical stimulation for bladder control following SCI, spanning from historic
      clinical approaches to recent pre-clinical studies that offer promising new
      strategies that may improve the feasibility and success of electrical stimulation
      therapy in patients with SCI. Electrical stimulation provides a unique
      opportunity to control bladder function by exploiting neural control mechanisms.
      Our understanding of the applications and limitations of electrical stimulation
      for bladder control has improved due to many pre-clinical studies performed in
      animals and translational clinical studies. Techniques that have emerged as
      possible opportunities to control bladder function include pudendal nerve
      stimulation and novel methods of stimulation, such as high frequency nerve block.
      Further development of novel applications of electrical stimulation will drive
      progress towards effective therapy for SCI. The optimal solution for restoration
      of bladder control may encompass a combination of efficient, targeted electrical
      stimulation, possibly at multiple locations, and pharmacological treatment to
      enhance symptom control. 

PMID- 25582566
TI  - The efficacy of a selamectin (Stronghold (r)) spot on treatment in the prevention
      of Bartonella henselae transmission by Ctenocephalides felis in cats, using a new
      high-challenge model.
AB  - Bartonella henselae is the causative agent of cat scratch disease in humans,
      which is recognized as an emerging zoonotic disease. Ctenocephalides felis is the
      main vector, and transmission of B. henselae infection between cats and humans
      occurs mainly through infected flea feces. Control of feline infestation with
      this arthropod vector therefore provides an important strategy for the prevention
      of infection of both humans and cats. In the present study, a new challenge model
      is used to evaluate the efficacy of selamectin (Stronghold((r)) spot on) in the
      prevention of B. henselae transmission by C. felis. In this new challenge model,
      domestic cats were infected by direct application of B. henselae-positive fleas.
      The fleas used for infestation were infected by feeding on blood that contained
      in vitro-cultured B. henselae. The direct application of the fleas to the animals
      and the use of different B. henselae strains ensured a high and consistent
      challenge. Two groups of six cats were randomly allocated on pre-treatment flea
      counts to either control (untreated cats) or the selamectin-treated group with
      one pipette per cat according to the label instruction. Stronghold (selamectin 6
      % spot on solution) was administered on days 0 and 32. On days 3, 10, 19, 25, and
      31, each cat was infested by direct application of 20 fleas that fed on blood
      inoculated with B. henselae. Polymerase chain reaction (PCR) on pooled fleas
      confirmed that the fleas were infected. Blood samples were collected from each
      cat on days -3 (prior to flea infestation and treatment), 9, 17, 24, 30, 37, and
      44 and assayed for B. henselae antibodies using an indirect immunofluorescence
      (IFA), for the presence of bacteria by bacterial culture and for B. henselae DNA
      presence by PCR. Cats were also assessed on a daily basis for general health.
      There were no abnormal health observations during the study and none of the
      animals required concomitant treatment. None of the cats displayed any clinical
      signs of bartonellosis during the study. In the untreated group, all cats became
      bacteremic within 17 to 44 days. None of the selamectin-treated cats became
      positive during the study. It was concluded that Stronghold((r)) spot on
      administered to cats was efficacious in the prevention of the transmission of B.
      henselae by fleas to cats in a high-challenge model.

PMID- 25582568
TI  - Wetting effect on optical sum frequency generation (SFG) spectra of d-glucose, d
      fructose, and sucrose.
AB  - We report a sum frequency generation (SFG) spectroscopy study of d-glucose, d
      fructose and sucrose in the CH stretching vibration regime. Wetting effect on the
      SFG spectra was investigated. The SFG spectrum of d-glucose changed from that of
      alpha-d-glucose into those of alpha-d-glucose monohydrate by wetting. The SFG
      spectra showed evidence of a small change of beta-d-fructopyranose into other
      anomers by wetting. SFG spectra of sucrose did not change by wetting. Assignments
      of the vibrational peaks in the SFG spectra of the three sugars in the dry and
      wet states were performed in the CH stretching vibration region near 3000cm(-1). 

PMID- 25582569
TI  - Ultrasound-enhanced attenuated total reflection mid-infrared spectroscopy in-line
      probe: acquisition of cell spectra in a bioreactor.
AB  - This article presents a novel method for selective acquisition of Fourier
      transform infrared (FT-IR) spectra of microorganisms in-line during fermentation,
      using Saccharomyces cerevisiae as an example. The position of the cells relative
      to the sensitive region of the attenuated total reflection (ATR) FT-IR probe was
      controlled by combing a commercially available ATR in-line probe with contact
      free, gentle particle manipulation by ultrasonic standing waves. A prototype
      probe was successfully constructed, assembled, and tested in-line during fed
      batch fermentations of S. cerevisiae. Control over the position of the cells was
      achieved by tuning the ultrasound frequency: 2.41 MHz was used for acquisition of
      spectra of the cells (pushing frequency f(p)) and 1.87 MHz, for retracting the
      cells from the ATR element, therefore allowing spectra of the medium to be
      acquired. Accumulation of storage carbohydrates (trehalose and glycogen) inside
      the cells was induced by a lack of a nitrogen source in the feed medium. These
      changes in biochemical composition were visible in the spectra of the cells
      recorded in-line during the application of f(p) and could be verified by
      reference spectra of dried cell samples recorded off-line with a FT-IR
      microscope. Comparison of the cell spectra with spectra of trehalose, glycogen,
      glucose, and mannan, i.e., the major carbohydrates present in S. cerevisiae, and
      principal components analysis revealed that the changes observed in the cell
      spectra correlated well with the bands specific for trehalose and glycogen. This
      proves the applicability and capability of ultrasound-enhanced in-line ATR mid-IR
      spectroscopy as a real-time PAT method for the in situ monitoring of cellular
      biochemistry during fermentation.

PMID- 25582570
TI  - Emerging functions of mammalian and plant mTERFs.
AB  - Organellar gene expression (OGE) is crucial for plant development, respiration
      and photosynthesis, but the mechanisms that control it are still largely unclear.
      Thus, OGE requires various nucleus-encoded proteins that promote transcription,
      splicing, trimming and editing of organellar RNAs, and regulate their
      translation. In mammals, members of the mitochondrial transcription termination
      factor (mTERF) family play important roles in OGE. Intriguingly, three of the
      four mammalian mTERFs do not actually terminate transcription, as their
      designation suggests, but appear to function in antisense transcription
      termination and ribosome biogenesis. During the evolution of land plants, the
      mTERF family has expanded to approximately 30 members, but knowledge of their
      function in photosynthetic organisms remains sparse. Here, we review recent
      advances in the characterization of mterf mutants in mammals and photosynthetic
      organisms, focusing particularly on the progress made in elucidating their
      molecular functions in the last two years. This article is part of a Special
      Issue entitled: Chloroplast biogenesis. 

PMID- 25582571
TI  - Molecular mechanism of photosystem I assembly in oxygenic organisms.
AB  - Photosystem I, an integral membrane and multi-subunit complex, catalyzes the
      oxidation of plastocyanin and the reduction of ferredoxin by absorbed light
      energy. Photosystem I participates in photosynthetic acclimation processes by
      being involved in cyclic electron transfer and state transitions for sustaining
      efficient photosynthesis. The photosystem I complex is highly conserved from
      cyanobacteria to higher plants and contains the light-harvesting complex and the
      reaction center complex. The assembly of the photosystem I complex is highly
      complicated and involves the concerted assembly of multiple subunits and hundreds
      of cofactors. A suite of regulatory factors for the assembly of photosystem I
      subunits and cofactors have been identified that constitute an integrative
      network regulating PSI accumulation. This review aims to discuss recent findings
      in the field relating to how the photosystem I complex is assembled in oxygenic
      organisms. This article is part of a Special Issue entitled: Chloroplast
      Biogenesis. 

PMID- 25582572
TI  - [Antibodies in dermatomyositis and other inflammatory myopathies: what the
      dermatologist must know].

PMID- 25582573
TI  - [Humanizing the hospital: an unending task].

PMID- 25582574
TI  - Human organic cation transporter 1 (hOCT1) as a mediator of bendamustine uptake
      and cytotoxicity in chronic lymphocytic leukemia (CLL) cells.
AB  - Bendamustine is used in the treatment of chronic lymphocytic leukemia (CLL).
      Routes for bendamustine entry into target cells are unknown. This study aimed at
      identifying transporter proteins implicated in bendamustine uptake. Our results
      showed that hOCT1 is a bendamustine transporter, as bendamustine could cis
      inhibit the uptake of a canonical hOCT1 substrate, with a Ki in the micromolar
      range, consistent with the EC50 values of the cytotoxicity triggered by this drug
      in HEK293 cells expressing hOCT1. hOCT1 polymorphic variants determining impaired
      bendamustine-transporter interaction, consistently reduced bendamustine
      cytotoxicity in HEK293 cells stably expressing them. Exome genotyping of the
      SLC22A1 gene, encoding hOCT1, was undertaken in a cohort of 241 CLL patients. Ex
      vivo cytotoxicity to bendamustine was measured in a subset of cases and shown to
      correlate with SLC22A1 polymorphic variants. In conclusion, hOCT1 is a suitable
      bendamustine transporter, thereby contributing to its cytotoxic effect depending
      upon the hOCT1 genetic variants expressed. 

PMID- 25582576
TI  - Clinical and epidemiological features of Guillain-Barre syndrome in the Western
      Balkans.
AB  - The aim of this study was to define features of Guillain-Barre syndrome in a
      large cohort of patients from three Western Balkans countries. Data from adult
      Guillain-Barre syndrome (GBS) cases from 2009 to 2013 were retrospectively
      obtained from all tertiary health care centers. During the 5-year period, 327 new
      cases of GBS were identified with a male to female ratio of 1.7 : 1. The most
      common GBS variants were demyelinating (65%) and axonal (12%). At nadir 45% of
      patients were chair-bound, confined to bed, or required assisted ventilation,
      while 5% died. The crude incidence of GBS in Serbia and Montenegro was 0.93 per
      100,000 population, and age-adjusted incidence according to the world standard
      population was 0.86 per 100,000. Incidence was particularly high in 50- to 80
      year-old men. Statistically significant seasonal variations of GBS were not
      observed. This study of patients with GBS in the Western Balkans allows us to
      prepare the health system better and to improve the management of patients. This
      study also opens opportunities for international collaboration and for taking
      part in the multinational studies on GBS.

PMID- 25582575
TI  - Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood
      acute lymphoblastic leukemia.
AB  - The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences
      the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1
      affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We
      studied 522 Danish children with ALL, 93% of all those eligible. Risk of relapse
      was increased 2.9-fold for patients with the 1199GA variant versus 1199GG
      (P=0.001), and reduced 61% and 40%, respectively, for patients with the 3435CT or
      3435TT variants versus 3435CC (overall P=0.02). The degree of bone marrow
      toxicity during doxorubicin, vincristine and prednisolone induction therapy was
      more prominent in patients with 3435TT variant versus 3435CT/3435CC
      (P=0.01/P<0.0001). We observed more liver toxicity after high-dose methotrexate
      in patients with 3435CC variant versus 3435CT/TT (P=0.03). In conclusion, there
      is a statistically significant association between ABCB1 polymorphisms, efficacy
      and toxicity in the treatment of ALL, and ABCB1 1199G>A may be a new possible
      predictive marker for outcome in childhood ALL. 

PMID- 25582577
TI  - Dissolution rate enhancement and physicochemical characterization of
      carbamazepine-poloxamer solid dispersions.
AB  - This study investigates the potential of poloxamers as solid dispersions (SDs)
      carriers in improving the dissolution rate of a poorly soluble drug,
      carbamazepine (CBZ). Solid dispersions were prepared with poloxamer 188 (P188)
      and poloxamer 407 (P407) by melting method in different drug:carrier ratios (1:1,
      1:2 and 1:3). Prepared samples were characterized using differential scanning
      calorimetry (DSC), hot-stage polarized light microscopy (HSM), powder X-ray
      diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) to
      investigate drug physical state within the SDs matrix, possible polymorphic
      transitions and drug-polymer interactions. The interactions between CBZ molecules
      and polymeric chains were also evaluated using molecular dynamics simulation
      (MDS) technique. The most thermodynamically stable polymorphic form III of CBZ
      was present in all SDs, regardless of the type of poloxamer and drug-to-carrier
      ratio. The absence of drug-polymer interactions was observed by FT-IR analysis
      and additionally confirmed by MDS. Formation of persistent hydrogen bond between
      two CBZ molecules, observed by MDS indicate high tendency of CBZ molecules to
      aggregate and form crystalline phase within dispersion. P188 exhibit higher
      efficiency in increasing CBZ dissolution rate due to its more pronounced
      hydrophilic properties, while increasing poloxamers concentration resulted in
      decreasing drug release rate, as a consequence of their thermoreversible
      gelation. 

PMID- 25582578
TI  - Combined diosmectite and mesalazine treatment for mild-to-moderate ulcerative
      colitis: a randomized, placebo-controlled study.
AB  - BACKGROUND: The relapse rate of ulcerative colitis (UC) is high. The efficacy of
      combined diosmectite and mesalazine treatment for active mild-to-moderate UC was
      investigated. MATERIAL/METHODS: A total of 120 patients with UC were enrolled in
      this randomized, single-blind, placebo-controlled study. Sixty patients were
      assigned to the Diosmectite group (diosmectite and mesalazine) and 60 were
      assigned to Placebo group (placebo and mesalazine). In the induction phase, the
      primary end point was the clinical remission rate at 8 weeks; secondary end
      points were clinical response, endothelial mucosal healing, Mayo score,
      erythrocyte sedimentation rate, C-reactive protein levels, and defecation
      frequency. In the maintenance phase, the primary end point was clinical remission
      at 52 weeks; secondary end points were clinical response, endothelial mucosal
      healing, Mayo score, erythrocyte sedimentation rate, and defecation frequency.
      RESULTS: At 8 weeks, the Diosmectite group had a significantly higher clinical
      remission rate (68.3% vs. 50%) and mucosal healing rate (66.7% vs. 48.3%)
      compared with the Placebo group. There were no significant differences in
      clinical response rates, Mayo score, erythrocyte sedimentation rate, C-reactive
      protein, or defecation frequency. At 52 weeks, the Diosmectite group had a
      significantly higher clinical remission rate (61.7% vs. 40%) and mucosal healing
      rate (60% vs. 38.3%) compared with the Placebo group. Defecation frequency was
      lower, but this was not significant. CONCLUSIONS: Combined diosmectite and
      mesalazine treatment successfully induced and maintained the treatment of active
      mild-to-moderate UC as indicated by higher rates of clinical remission and
      mucosal healing.

PMID- 25582581
TI  - Methylated Re(I) tetrazolato complexes: photophysical properties and Light
      Emitting Devices.
AB  - The irreversible reaction of methyl triflate with neutral Re(I) tetrazolato
      complexes of the type fac-[Re(diim)(CO)3(L)], where diim is either 1,10
      phenanthroline or 2,2'-bipyridine and L is a para substituted 5-aryltetrazolate,
      yielded the corresponding cationic methylated complexes. While methylation
      occurred regioselectively at the N4 position of the tetrazole ring, the cationic
      complexes were found to exist in solution as equilibrating mixtures of linkage
      isomers, where the Re(i) centre was bound to either the N1 or N2 atom of the
      tetrazole ring. The existence of these isomers was highlighted both by NMR and X
      ray crystallography studies. On the other hand, the two isomers appeared
      indistinguishable by IR, UV-Vis and luminescence spectroscopy. The prepared
      cationic complexes are all brightly phosphorescent in fluid and rigid solutions,
      with emission originating from triplet metal-to-ligand charge transfer excited
      states. Compared to their neutral precursors, which emit from admixtures of
      triplet metal-to-ligand and ligand-to-ligand charge transfer states, the
      methylated complexes exhibit blue-shifted emission characterised by elongated
      excited state lifetimes and increased quantum yields. The nature of the excited
      states for both the neutral and the methylated complexes was probed by resonance
      Raman spectroscopy and with the aid of time-dependent density functional theory
      calculations. Lastly, both the neutral and the methylated species were used as
      emitting phosphors in the fabrication of Organic Light Emitting Diodes and Light
      Emitting Electrochemical Cells.

PMID- 25582582
TI  - Maternal treatment with fluoxetine promotes testicular alteration in male rat
      pups.
AB  - Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI)
      antidepressant commonly prescribed during pregnancy and lactation. Pre- and post
      partum depression, as well as SSRI treatment during these periods, may change
      maternal care, interfering with offspring development. Moreover, it is known that
      SSRIs may alter testes structure and function in offspring. The present study
      investigated the effects of maternal FLX exposure on maternal behaviour and
      testes function in offspring. Female Wistar rats were treated with 7.5mgkg-1 FLX
      or tap water (control group) by gavage from the Day 1 of pregnancy until 21 days
      after birth (postnatal Day (PND) 21). Maternal behaviour was evaluated and
      morphofunctional analyses of offspring testes were conducted on PND 21 and 50.
      There were no significant differences between the FLX-treated and control groups
      regarding maternal behaviour. Nor did maternal treatment with FLX have any effect
      on bodyweight gain, anogenital distance, day of preputial separation, testis
      weight and the gonadosomatic index in male offspring. However, there was a
      decreased number of Sertoli cells at both PND 21 and 50 in FLX-exposed male
      offspring. The findings of the present study demonstrate that maternal exposure
      to FLX can impair testicular function in weanling and pubertal animals.

PMID- 25582580
TI  - Human spinal locomotor control is based on flexibly organized burst generators.
AB  - Constant drive provided to the human lumbar spinal cord by epidural electrical
      stimulation can cause local neural circuits to generate rhythmic motor outputs to
      lower limb muscles in people paralysed by spinal cord injury. Epidural spinal
      cord stimulation thus allows the study of spinal rhythm and pattern generating
      circuits without their configuration by volitional motor tasks or task-specific
      peripheral feedback. To reveal spinal locomotor control principles, we studied
      the repertoire of rhythmic patterns that can be generated by the functionally
      isolated human lumbar spinal cord, detected as electromyographic activity from
      the legs, and investigated basic temporal components shared across these
      patterns. Ten subjects with chronic, motor-complete spinal cord injury were
      studied. Surface electromyographic responses to lumbar spinal cord stimulation
      were collected from quadriceps, hamstrings, tibialis anterior, and triceps surae
      in the supine position. From these data, 10-s segments of rhythmic activity
      present in the four muscle groups of one limb were extracted. Such samples were
      found in seven subjects. Physiologically adequate cycle durations and relative
      extension- and flexion-phase durations similar to those needed for locomotion
      were generated. The multi-muscle activation patterns exhibited a variety of
      coactivation, mixed-synergy and locomotor-like configurations. Statistical
      decomposition of the electromyographic data across subjects, muscles and samples
      of rhythmic patterns identified three common temporal components, i.e. basic or
      shared activation patterns. Two of these basic patterns controlled muscles to
      contract either synchronously or alternatingly during extension- and flexion-like
      phases. The third basic pattern contributed to the observed muscle activities
      independently from these extensor- and flexor-related basic patterns. Each
      bifunctional muscle group was able to express both extensor- and flexor-patterns,
      with variable ratios across the samples of rhythmic patterns. The basic
      activation patterns can be interpreted as central drives implemented by spinal
      burst generators that impose specific spatiotemporally organized activation on
      the lumbosacral motor neuron pools. Our data thus imply that the human lumbar
      spinal cord circuits can form burst-generating elements that flexibly combine to
      obtain a wide range of locomotor outputs from a constant, repetitive input. It
      may be possible to use this flexibility to incorporate specific adaptations to
      gait and stance to improve locomotor control, even after severe central nervous
      system damage. 

PMID- 25582579
TI  - Evidence for brain glial activation in chronic pain patients.
AB  - Although substantial evidence has established that microglia and astrocytes play
      a key role in the establishment and maintenance of persistent pain in animal
      models, the role of glial cells in human pain disorders remains unknown. Here,
      using the novel technology of integrated positron emission tomography-magnetic
      resonance imaging and the recently developed radioligand (11)C-PBR28, we show
      increased brain levels of the translocator protein (TSPO), a marker of glial
      activation, in patients with chronic low back pain. As the Ala147Thr polymorphism
      in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control
      pairs were identified from a larger sample of subjects screened and genotyped,
      and compared in a matched-pairs design, in which each patient was matched to a
      TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two
      Ala/Thr, five males and four females in each group; median age difference: 1
      year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake
      values normalized to whole brain were significantly higher in patients than
      controls in multiple brain regions, including thalamus and the putative
      somatosensory representations of the lumbar spine and leg. The thalamic levels of
      TSPO were negatively correlated with clinical pain and circulating levels of the
      proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts
      pain-protective/anti-inflammatory effects in humans, as predicted by animal
      studies. Given the putative role of activated glia in the establishment and or
      maintenance of persistent pain, the present findings offer clinical implications
      that may serve to guide future studies of the pathophysiology and management of a
      variety of persistent pain conditions. 

PMID- 25582583
TI  - Novel export control of a Legionella Dot/Icm substrate is mediated by dual,
      independent signal sequences.
AB  - The Legionella pneumophila Dot/Icm T4SS injects ~ 300 protein effector proteins
      into host cells. Dot/Icm substrates have been proposed to contain a carboxy
      terminal signal sequence that is necessary and sufficient for export, although
      both traits have been demonstrated for only a small fraction of these proteins.
      In this study, we discovered that export of the substrate SidJ is mediated by
      dual signal sequences that include a conventional C-terminal domain and a novel
      internal motif. The C-terminal signal sequence facilitates secretion of SidJ into
      host cells at early points of infection, whereas the internal signal sequence
      mediates secretion at later time points. Interestingly, only the internal signal
      sequence is necessary for complementation of the intracellular growth defect of a
      DeltasidJ mutant. Although this is the first report of a Dot/Icm substrate being
      secreted by an internal signal sequence, many other substrates may be exported in
      a similar manner. In addition, efficient translocation of SidJ is dependent on
      the chaperone-like type IV adaptors IcmS/IcmW. Five IcmS/IcmW binding domains
      that are distinct from both signal sequences were elucidated and, interestingly,
      only secretion mediated by the internal signal sequence requires IcmS/IcmW. Thus,
      Legionella employs multiple sophisticated molecular mechanisms to regulate the
      export of SidJ. 

PMID- 25582584
TI  - Effect of adjuncts on microbiological and chemical properties of Scamorza cheese.
AB  - Scamorza is a semi-hard, pasta filata cheese resembling low-moisture Mozzarella
      cheese, with a short ripening time (<30d). Scamorza has a bland flavor and, to
      provide diversification from similar cheeses, it was manufactured using 2 types
      of milk in the current study: 100% Italian Friesian milk (F) or 90% F and 10%
      Jersey cow milk (mixed, M), and 2 types of starter: Streptococcus thermophilus or
      S. thermophilus with peptidolytic Lactococcus lactis, Lactobacillus helveticus,
      and Lactobacillus paracasei strains as adjuncts). The cheeses were ripened for
      30d. The adjunct did not significantly affect acid production or growth of the
      primary starter; 2 of the species used in the adjunct (Lb. paracasei and Lb.
      helveticus) rapidly colonized the cheese and persisted until the end of ripening,
      whereas the counts of nonstarter lactic acid bacteria in the control cheese were
      low until the end of ripening. The use of adjuncts affected pH, microbial
      composition (as assessed by both culture-dependent and culture-independent
      methods), total free amino acid content, and volatile profile (measured using an
      electronic nose), whereas milk type had only a minor effect. Although differences
      in primary proteolysis were found, they were probably indirect and related to the
      effects on pH and moisture. We conclude that, even with a short ripening time
      (30d), use of a peptidolytic adjunct may significantly affect important features
      of Scamorza and may be used to create a product that is measurably different from
      competing products. 

PMID- 25582585
TI  - Invited review: An evaluation of the likely effects of individualized feeding of
      concentrate supplements to pasture-based dairy cows.
AB  - In pasture-based dairy systems, supplementary feeds are used to increase dry
      matter intake and milk production. Historically, supplementation involved the
      provision of the same amount of feed (usually a grain-based concentrate feed) to
      each cow in the herd during milking (i.e., flat-rate feeding). The increasing
      availability of computerized feeding and milk monitoring technology in milking
      parlors, however, has led to increased interest in the potential benefits of
      feeding individual cows (i.e., individualized or differential feeding) different
      amounts and types of supplements according to one or more parameters (e.g.,
      breeding value for milk yield, current milk yield, days in milk, body condition
      score, reproduction status, parity). In this review, we consider the likely
      benefits of individualized supplementary feeding strategies for pasture-based
      dairy cows fed supplements in the bail during milking. A unique feature of our
      review compared with earlier publications is the focus on individualized feeding
      strategies under practical grazing management. Previous reviews focused primarily
      on research undertaken in situations where cows were offered ad libitum forage,
      whereas we consider the likely benefits of individualized supplementary feeding
      strategies under rotational grazing management, wherein pasture is often
      restricted to all or part of a herd. The review provides compelling evidence that
      between-cow differences in response to concentrate supplements support the
      concept of individualized supplementary feeding. 

PMID- 25582586
TI  - Evaluation of on-farm tools for colostrum quality measurement.
AB  - The objectives of this study were to determine the immunoglobulin G (IgG) content
      of colostrum on Alberta dairy farms and to determine which on-farm tool, the
      colostrometer or the Brix refractometer, was more highly correlated with IgG
      content as determined by radial immunodiffusion (RID). Colostrum samples (n=569)
      were collected between February and July 2012 from 13 commercial dairy farms in
      central Alberta, with herds ranging in size from 60 to 300 lactating cows.
      Immunoglobulin G content was determined directly by RID and indirectly by a
      colostrometer (specific gravity) and Brix refractometer (total solids). The
      Spearman correlation was used for the colostrometer and Brix refractometer data.
      According to RID analysis, 29.1% of the colostrum samples contained <50 mg/mL
      IgG. Concentrations ranged from 8.3 to 128.6 mg/mL IgG, with a median of 65.1
      mg/mL. Third or greater parity cows had higher colostral IgG content (69.5+/-1.98
      mg/mL) than second parity (59.80+/-2.06 mg/mL) or first parity (62.2+/-1.73
      mg/mL) cows. The colostrometer data were more highly correlated with RID results
      (r=0.77) than were the Brix refractometer data (r=0.64). Specificity and
      sensitivity were determined for the colostrometer and Brix refractometer compared
      with a cut-point of 50 mg/mL IgG as determined by RID. The highest combined value
      for sensitivity and specificity occurred at 80 mg/mL for the colostrometer (84.1
      and 77.0%, respectively) and 23% Brix (65.7 and 82.8%, respectively). This study
      indicates that although the colostrometer data are better correlated with true
      IgG values, the user-friendly Brix refractometer is a more specific tool to
      detect colostrum of adequate quality.

PMID- 25582588
TI  - Manufacture and characterization of kefir made from cow and buffalo milk, using
      kefir grain and starter culture.
AB  - The microbiological and chemical characteristics as well as organic and amino
      acid profiles of kefir samples made from cow and buffalo milks fermented by kefir
      grains and starter culture were investigated during storage for 21 d at 4 degrees
      C. After incubation, lactic, acetic, and citric acid concentrations showed a
      difference among the samples due to milk type and production methods. Storage
      time had little effect on the organic acid values of kefir samples. As compared
      with cow milk kefir, buffalo milk kefir had higher numbers of microorganisms,
      except lactobacilli, at the end of storage. Whereas pH and titratable acidity
      exhibited similar changes during storage in all kefir samples, ethanol levels
      were significantly increased in buffalo milk kefir samples. Glutamic acid was the
      major amino acid at all sampling times for all samples. Tyrosine, serine,
      histidine, alanine, methionine, and lysine concentrations were determined to be
      different in all samples depending on milk type. In general, due to the higher
      microbial population (especially yeast), kefir made from buffalo milk may be
      preferred.

PMID- 25582587
TI  - Propidium monoazide combined with real-time PCR for selective detection of viable
      Staphylococcus aureus in milk powder and meat products.
AB  - Staphylococcus aureus is a spherical, gram-positive, pathogenic bacterium
      commonly associated with bovine mastitis and clinical infections. It is also
      recognized as a pathogen that causes outbreaks of food poisoning. The objective
      of this study was to develop and evaluate a rapid and reliable technique that
      combines propidium monoazide (PMA) staining with real-time quantitative (q)PCR to
      detect and quantify viable cells of Staph. aureus in milk powder and meat
      products. The inclusivity and exclusivity of the assay were evaluated using 58
      strains belonging to 14 species. Serial dilutions of Staph. aureus cells were
      used to establish a standard curve and to confirm the effect of PMA treatment.
      Milk powder and meat products were used as the spiked foods, and the ability of
      PMA-qPCR to eliminate nonviable cells was determined in milk powder. Furthermore,
      meat products were inoculated with different concentrations of Staph. aureus and
      10(5) cfu/g of Bacillus cereus and Salmonella enterica to test the interference
      by nontarget microorganisms. When PMA treatment was applied before DNA
      extraction, we were able to eliminate false-positive results with little effect
      on viable cells. The PMA-qPCR assay was specific and more sensitive than
      conventional PCR, and the level of detection was 3.0*10(2) cfu/g in spiked milk
      powder. Additionally, we observed no significant interference for the detection
      of viable Staph. aureus from other nontarget bacteria. The PMA-qPCR protocol is
      an effective and rapid method to quantify viable cells of Staph. aureus in food
      samples. The PMA-qPCR assay is specific and reliable, offering a valuable
      diagnostic tool for routine analysis in food and clinical diagnostic research at
      a reasonable cost. 

PMID- 25582589
TI  - Heterogeneity in genetic and nongenetic variation and energy sink relationships
      for residual feed intake across research stations and countries.
AB  - Our long-term objective is to develop breeding strategies for improving feed
      efficiency in dairy cattle. In this study, phenotypic data were pooled across
      multiple research stations to facilitate investigation of the genetic and
      nongenetic components of feed efficiency in Holstein cattle. Specifically, the
      heritability of residual feed intake (RFI) was estimated and heterogeneous
      relationships between RFI and traits relating to energy utilization were
      characterized across research stations. Milk, fat, protein, and lactose
      production converted to megacalories (milk energy; MilkE), dry matter intakes
      (DMI), and body weights (BW) were collected on 6,824 lactations from 4,893
      Holstein cows from research stations in Scotland, the Netherlands, and the United
      States. Weekly DMI, recorded between 50 to 200 d in milk, was fitted as a linear
      function of MilkE, BW0.75, and change in BW (DeltaBW), along with parity, a fifth
      order polynomial on days in milk (DIM), and the interaction between this
      polynomial and parity in a first-stage model. The residuals from this analysis
      were considered to be a phenotypic measure of RFI. Estimated partial regression
      coefficients of DMI on MilkE and on BW0.75 ranged from 0.29 to 0.47 kg/Mcal for
      MilkE across research stations, whereas estimated partial regression coefficients
      on BW0.75 ranged from 0.06 to 0.16 kg/kg0.75. Estimated partial regression
      coefficients on DeltaBW ranged from 0.06 to 0.39 across stations. Heritabilities
      for country-specific RFI were based on fitting second-stage random regression
      models and ranged from 0.06 to 0.24 depending on DIM. The overall heritability
      estimate across all research stations and all DIM was 0.15+/-0.02, whereas an
      alternative analysis based on combining the first- and second-stage model as 1
      model led to an overall heritability estimate of 0.18+/-0.02. Hence future
      genomic selection programs on feed efficiency appear to be promising;
      nevertheless, care should be taken to allow for potentially heterogeneous
      variance components and partial relationships between DMI and other energy sink
      traits across environments when determining RFI.

PMID- 25582590
TI  - Enteric methane production, rumen volatile fatty acid concentrations, and milk
      fatty acid composition in lactating Holstein-Friesian cows fed grass silage- or
      corn silage-based diets.
AB  - The objective of this study was to determine the effects of replacing grass
      silage (GS) with corn silage (CS) in dairy cow diets on enteric methane (CH4)
      production, rumen volatile fatty acid concentrations, and milk fatty acid (FA)
      composition. A completely randomized block design experiment was conducted with
      32 multiparous lactating Holstein-Friesian cows. Four dietary treatments were
      used, all having a roughage-to-concentrate ratio of 80:20 based on dry matter
      (DM). The roughage consisted of either 100% GS, 67% GS and 33% CS, 33% GS and 67%
      CS, or 100% CS (all DM basis). Feed intake was restricted (95% of ad libitum DM
      intake) to avoid confounding effects of DM intake on CH4 production. Nutrient
      intake, apparent digestibility, milk production and composition, nitrogen (N) and
      energy balance, and CH4 production were measured during a 5-d period in climate
      respiration chambers after adaptation to the diet for 12 d. Increasing CS
      proportion linearly decreased neutral detergent fiber and crude protein intake
      and linearly increased starch intake. Milk production and milk fat content (on
      average 23.4 kg/d and 4.68%, respectively) were not affected by increasing CS
      inclusion, whereas milk protein content increased quadratically. Rumen variables
      were unaffected by increasing CS inclusion, except the molar proportion of
      butyrate, which increased linearly. Methane production (expressed as grams per
      day, grams per kilogram of fat- and protein-corrected milk, and as a percent of
      gross energy intake) decreased quadratically with increasing CS inclusion, and
      decreased linearly when expressed as grams of CH4 per kilogram of DM intake. In
      comparison with 100% GS, CH4 production was 11 and 8% reduced for the 100% CS
      diet when expressed per unit of DM intake and per unit fat- and protein-corrected
      milk, respectively. Nitrogen efficiency increased linearly with increased
      inclusion of CS. The concentration of trans C18:1 FA, C18:1 cis-12, and total CLA
      increased quadratically, and iso C16:0, C18:1 cis-13, and C18:2n-6 increased
      linearly, whereas the concentration of C15:0, iso C15:0, C17:0, and C18:3n-3
      decreased linearly with increasing inclusion of CS. No differences were found in
      short- and medium-straight, even-chain FA concentrations, with the exception of
      C4:0 which increased linearly with increased inclusion of CS. Replacing GS with
      CS in a common forage-based diet for dairy cattle offers an effective strategy to
      decrease enteric CH4 production without negatively affecting dairy cow
      performance, although a critical level of starch in the diet seems to be needed.

PMID- 25582591
TI  - The effect of manual and mechanical stimulation on oxytocin release and milking
      characteristics in Holstein cows milked 3 times daily.
AB  - Prestimulation administered to a cow before attachment of the milking unit has
      historically been performed manually. Development of innovative milking
      technology has allowed manual stimulation to be replaced by mechanical forms of
      stimulation. Holstein cows (n=30) were enrolled in a crossover design to
      determine the effect of manual stimulation (forestripping and drying) and high
      vibration pulsation on oxytocin profiles, milk yield, milk flow rates, incidence
      of delayed milk ejection causing bimodal milk flow curves, and residual milk in
      Holstein cows milked 3 times daily (3*). All cows were subjected to all
      treatments. Cows received manual (forestripping and drying) or mechanical (high
      vibration pulsation) stimulation along with lag times of 0, 30, or 90 s for 21
      consecutive milkings. Forestripping involved the manual removal of 2 streams of
      milk from each teat and drying of the teats. High-vibration pulsation involved
      increasing the pulsation cycles from 60 to 300 pulses/min and reducing the vacuum
      in the pulsation chamber to 20 kPa. The 5 treatments were (1) immediate
      attachment of the milking machine under normal pulsation (T0); (2) dip plus
      forestrip and drying with 30-s lag time (FD30); (3) dip plus forestrip and drying
      with 90-s lag time (FD90); (4) high-vibration pulsation for 30 s (HV30); and (5)
      high-vibration pulsation for 90 s (HV90). Milk yield per milking averaged 14.0 kg
      and was significantly different among treatments; however, the maximum difference
      detected among treatments was 0.8 kg/milking. Milking unit on-time, which
      represents the time when the milking unit is under normal pulsation and
      harvesting milk (excluding the high-vibration pulsation time of 30 or 90 s), was
      shortest (245 s) for cows subjected to 90 s of high-vibration pulsation (HV90)
      and ranged from 256 to 261 s for all other treatments. Milk harvest may have
      begun during high-vibration pulsation; however, only 0.13 and 0.32 kg of milk was
      harvested during high-vibration pulsation for HV30 and HV90, respectively. The
      incidence of bimodal milk curves was lowest for FD90 (7%) and highest for T0
      (21%). The somatic cell count was <72*10(3) cells/mL for all treatments. Residual
      milk obtained by giving 10 IU of oxytocin in the jugular vein followed by 2 min
      of milking unit attachment represented 12 to 14% of the total milk and did not
      differ among treatments. Endogenous oxytocin profiles peaked between 12.4 and
      18.3 pg/mL for all treatments, and the peak occurred sooner in manually
      stimulated cows; however, we detected no difference in oxytocin concentration
      beyond 2 min after milking unit attachment. High-vibration pulsation elicited a
      similar oxytocin release when taking the start time of stimulation from manual
      stimulation or high vibration into consideration. Forestripping for visual
      observation of milk combined with the use of high-vibration stimulation may
      reduce variation in the milking routine. A predetermined lag time with minimal
      variation may be achieved via the time spent in high-vibration stimulation
      instead of a lag period dictated by milking personnel.

PMID- 25582592
TI  - Predictive value of masseter muscle thickness and bite force on Class II
      functional appliance treatment: a prospective controlled study.
AB  - AIM: To prospectively evaluate the functional capacity of the masticatory
      musculature as a predictive variable in determining functional appliance
      treatment outcomes in Class II/1 malocclusion children. METHODS: Twenty Class
      II/1 malocclusion children (11.4 +/- 1.7 years) were treated with functional
      appliances during 1 year. Masseter muscle thickness and maximal molar bite force
      measurements, lateral cephalograms, and study casts were taken before and after
      treatment. Twenty age- and gender-matched untreated children were included as a
      control group. Regression analyses were used to identify correlations between pre
      treatment muscle characteristics and treatment outcomes. RESULTS: All treated
      patients showed dentoalveolar sagittal improvement. Maximal molar bite force and
      masseter muscle thickness decreased during the treatment period in the
      experimental group but increased in the control group. Children with lower pre
      treatment maximal molar bite force showed more mesial movement of mandibular
      first molars, distal movement of maxillary first molars, and larger change in
      molar class during treatment. Children with thinner pre-treatment masseter
      muscles demonstrated more mandibular first molar mesialisation, mandibular
      incisor proclination, and opening of the gonial angle during treatment.
      CONCLUSIONS: The initial condition of the masticatory muscles may partly
      determine treatment outcomes. Children with thinner pre-treatment masseter
      muscles or weaker bite force show greater dentoalveolar changes.

PMID- 25582593
TI  - Reassessing the "duon" hypothesis of protein evolution.
AB  - There are two distinct types of DNA sequences, namely coding sequences and
      regulatory sequences, in a genome. A recent study of the occupancy of
      transcription factors (TFs) in human cells suggested that protein-coding
      sequences also serve as the codes of TF occupancy, and proposed a "duon"
      hypothesis in which up to 15% of codons of human protein genes are constrained by
      the additional coding requirements that regulate gene expression. This hypothesis
      challenges our basic understanding on the human genome. We reanalyzed the data
      and found that the previous study was confounded by ascertainment bias related to
      base composition. Using an unbiased comparison in which G/C and A/T sites are
      considered separately, we reveal a similar level of conservation between TF-bound
      codons and TF-depleted codons, suggesting largely no extra purifying selection
      provided by the TF occupancy on the codons of human genes. Given the generally
      short binding motifs of TFs and the open chromatin structure during
      transcription, we argue that the occupancy of TFs on protein-coding sequences is
      mostly passive and evolutionarily neutral, with to-be-determined functions in the
      regulation of gene expression. 

PMID- 25582594
TI  - Genetic enablers underlying the clustered evolutionary origins of C4
      photosynthesis in angiosperms.
AB  - The evolutionary accessibility of novel adaptations varies among lineages,
      depending in part on the genetic elements present in each group. However, the
      factors determining the evolutionary potential of closely related genes remain
      largely unknown. In plants, CO2-concentrating mechanisms such as C4 and
      crassulacean acid metabolism (CAM) photosynthesis have evolved numerous times in
      distantly related groups of species, and constitute excellent systems to study
      constraints and enablers of evolution. It has been previously shown for multiple
      proteins that grasses preferentially co-opted the same gene lineage for C4
      photosynthesis, when multiple copies were present. In this work, we use
      comparative transcriptomics to show that this bias also exists within
      Caryophyllales, a distantly related group with multiple C4 origins. However, the
      bias is not the same as in grasses and, when all angiosperms are considered
      jointly, the number of distinct gene lineages co-opted is not smaller than that
      expected by chance. These results show that most gene lineages present in the
      common ancestor of monocots and eudicots produced gene descendants that were
      recruited into C4 photosynthesis, but that C4-suitability changed during the
      diversification of angiosperms. When selective pressures drove C4 evolution, some
      copies were preferentially co-opted, probably because they already possessed C4
      like expression patterns. However, the identity of these C4-suitable genes varies
      among clades of angiosperms, and C4 phenotypes in distant angiosperm groups thus
      represent genuinely independent realizations, based on different genetic
      precursors. 

PMID- 25582595
TI  - Duration of untreated psychosis and pathway to care in Riyadh, Saudi Arabia.
AB  - AIM: Recent studies of 'duration of untreated psychosis' (DUP) indicate that some
      patients remain untreated in the community for some time. Considerable emphasis
      has been placed on reducing the DUP. However, most studies investigating DUP have
      been conducted in Western countries, where well-developed primary care systems
      are available. This study aims to describe DUP and its association with both
      demographic factors and pathways to care in Riyadh, Saudi Arabia. METHODS: A
      retrospective study of 421 new case records of all Saudi schizophrenia patients
      over a 2-year period in six governmental hospitals in Riyadh, Saudi Arabia.
      RESULTS: The median DUP was 1.41 years (interquartile range 0.35-2.81 years). The
      longest time to contact was 9.86 years but 90% had a DUP shorter than 5 years.
      Older age at onset, single marital status and higher educational level were
      associated with shorter DUP. Long DUP was associated with help seeking from
      traditional healers. CONCLUSION: In Saudi Arabia, it usually takes longer for
      patients to seek help from psychiatric services after their first psychosis onset
      than it does in Western countries. The results suggest that the DUP is influenced
      by both demographic factors and pathways to care.

PMID- 25582596
TI  - Age-related regional deterioration patterns and changes in nanoscale
      characterizations of trabeculae in the femoral head.
AB  - This study aimed to investigate the mechanical properties and features of bone
      materials at the nanoscale level in different regions of the femoral head in
      elderly patients with femoral neck fracture. Ten femoral heads from female
      patients with femoral neck fractures were extracted during surgery (five for the
      Aged group, aged 65-66 years; five for the Advanced aged group, aged 85-95
      years). The femoral head was divided into three equal layers (anterior, central,
      and posterior) in the coronal view, and each layer was segmented into five
      regions (superior, central, inferior, medial, and lateral). Nanoindentation
      testing and atomic force microscopy imaging were used to study the mechanical
      properties and surface morphology of the specimens. No statistical differences in
      grain size were found between age groups, which suggested that the nanostructure
      of trabeculae in the femoral heads of postmenopausal women cannot be used to
      predict age-related bone loss and fracture risk. Mechanical properties in the
      longitudinal direction deteriorated more quickly than those in the transverse
      direction for the whole femoral head. Comparisons between layers showed a higher
      deterioration rate with aging in the anterior layer than in other layers. In
      different regions, mechanical properties of the medial and lateral regions
      deteriorated more quickly than those in the three other regions, and
      deterioration in the longitudinal direction was more serious than that in the
      transverse direction. The regional deterioration patterns and material properties
      with aging observed in this study contribute to an understanding of the age
      related fracture mechanism and provide a basis for predicting age-related
      fracture risk and decreasing early fixation failure in the proximal femur.

PMID- 25582597
TI  - A new iridoid, verbascoside and derivatives with inhibitory activity against Taq
      DNA polymerase.
AB  - DNA polymerases are enzymes that play a crucial role in DNA metabolism such as
      replication, repair, transcription, recombination, and chromosome segregation
      during mitosis. Herein we report the isolation of a new iridoid (6-epi-catalpol,
      2) and per-O-acetyl-verbascoside (11) from aerial part of Buddleja cordobensis
      Grisebach (Buddlejaceae). From compound 2, we have obtained eight compounds by
      chemical transformation. This group of compounds at a concentration of 500MUM was
      assayed against Taq DNA polymerase. Compound 11 (per-O-acetyl-verbascoside) was
      the most active with an IC50 of 1.21+/-0.18MUM; compounds 9, 2 and 8 were strong
      inhibitors with IC50 values of 5.57+/-0.70, 21.62+/-0.22 and 78.13+/-0.93MUM,
      respectively. Compounds 11 and 9 could be a leader structures to development new
      anticancer chemotherapy medicines and a useful tool to investigate DNA polymerase
      activity. 

PMID- 25582598
TI  - Development of novel Asf1-H3/H4 inhibitors.
AB  - The histone chaperone anti-silencing function 1 (Asf1) has emerged as a promising
      target for therapeutic intervention for multiple cancers (Cell2006, 127, 458).
      Asf1 is involved in the packaging of the eukaryotic genome into chromatin, which
      is essential for normal growth, development, and differentiation, as this
      regulates all nuclear processes that use DNA as a substrate. Starting from a
      collection of HTS leads, we identified a series of N-acyl hydrazones as novel
      inhibitors of the Asf-histone H3/H4 interaction. These compounds represent the
      first example of inhibitors capable of disrupting the Asf1-H3/H4 complex. 

PMID- 25582600
TI  - Discovery of indole-derived pyridopyrazine-1,6-dione gamma-secretase modulators
      that target presenilin.
AB  - Herein we describe design strategies that led to the discovery of novel
      pyridopyrazine-1,6-dione gamma-secretase modulators (GSMs) incorporating an
      indole motif as a heterocyclic replacement for a naphthyl moiety that was present
      in the original lead 9. Tactics involving parallel medicinal chemistry and in
      situ monomer synthesis to prepare focused libraries are discussed. Optimized
      indole GSM 29 exhibited good alignment of in vitro potency and physicochemical
      properties, and moderate reduction of brain Abeta42 was achieved in a rat
      efficacy model when dosed orally at 30mg/kg. Labeling experiments using a
      clickable, indole-derived GSM photoaffinity probe demonstrated that this series
      binds to the presenilin N-terminal fragment (PS1-NTF) of the gamma-secretase
      complex. 

PMID- 25582599
TI  - The combination of thioxodihydroquinazolinones and platinum drugs reverses
      platinum resistance in tumor cells by inducing mitochondrial apoptosis
      independent of Bax and Bak.
AB  - The effective management of tumors resistant to platinum drugs-based anticancer
      therapies is a critical challenge in current clinical practices. The proapoptotic
      Bcl-2 family proteins Bax and Bak are essential for cisplatin-induced apoptosis.
      Unfortunately, Bax and its related upstream endogenous apoptotic signaling
      pathways are often dysregulated in cancer cells. Strategies that are able to
      bypass Bax- and Bak-dependent apoptotic pathways will thus provide opportunities
      to overcome platinum drug resistance. We have identified the
      thioxodihydroquinazolinone mdivi-1 as a member of a novel class of small
      molecules that are able to induce Bax- and Bak-independent mitochondrial outer
      membrane permeabilization when combined with cisplatin, thereby efficiently
      triggering apoptosis in platinum-resistant tumor cells. In the present structure
      activity relationship (SAR) study of a computationally selected library of mdivi
      1 related small molecules, we established a pharmacophore model that can lead to
      the enhancement of platinum drug efficacy and Bax/Bak-independent mitochondrial
      apoptosis. Specifically, we found that a thiourea function is necessary but not
      sufficient for the synergism of this class of thioxodihydroquinazolinones with
      cisplatin. We were also able to identify more potent mdivi-1 analogs through this
      SAR study, which will guide future designs with the goal to develop novel
      combination regimens for the treatment of platinum- and multidrug-resistant
      tumors. 

PMID- 25582601
TI  - Design of novel CSA analogues as potential safeners and fungicides.
AB  - Study of safeners has been seldom reported in literature. In this work, a series
      of novel acylsulfamoylbenzamide analogues was designed and synthesized with newly
      developed safener cyprosulfamide (CSA) as the leading compound. The activity
      assay against the herbicide thiencarbazone-methyl (TCM) on maize revealed that
      fifteen compounds showed better protective effect than CSA on the fresh weight of
      aerial parts, twelve compounds exhibited better activity on the dry weight of
      aerial parts. Remarkably, two compounds (6Ih, 7II) had protective effect on the
      four aspects of TCM treated maize. Further antifungal assay showed their
      excellent activity against Physollospora piricola. The structure-activity
      relationships of CSA analogues as safeners and fungicides were discussed and it
      might be valuable for further molecular modification of new CSA analogues. 

PMID- 25582602
TI  - Structure-activity relationships of diverse ACGs against multidrug resistant
      human lung cancer cell line A549/Taxol.
AB  - Fifteen annonaceous acetogenins (ACGs) with different stereochemical structures
      and configuration, representing three main classes of bis-adjacent
      tetrahydrofuran (THF), bis-nonadjacent-THF, and mono-THF ACGs, were selected to
      tested for their inhibition activity on A549/Taxol cell line, which is multidrug
      resistant (MDR). The present study showed that some tested compounds showed
      significant activity toward A549/Taxol cells, and were more potent than the
      positive control Verapamil. For example, squamostatin-D (14) (IC50
      value=16.19MUM) was 7.8 times more active than Verapamil (IC50 value=127.09MUM).
      Those ACGs with more carbons between the THF ring and the gamma-unsaturated
      lactone were more potent. Moreover, ACGs with stereochemical arrangement of
      erythro were more active than those of threo, the compounds with THF ring
      configuration of cis seemed to be superior to those of trans. However, if all
      other structural features were identical, the ACGs with more hydroxyls on the
      aliphatic chain were not more potent towards A549/Taxol, which was not in
      accordance with previous studies. Furthermore, bis-nonadjacent-THF ACGs whose
      molecular weight is 622, with three hydroxyl groups located at carbon 16, 19, 24
      and stereochemical arrangement of erythro possibly produced notable cytotoxicity.
      Based on the above conclusions, we proposed a compound model that may be a
      promising anti-MDR cancer candidate drug in the future clinical trial. 

PMID- 25582603
TI  - [Malignization of a choledocal cyst in the adult: A rare entity].

PMID- 25582604
TI  - Bovine mastitis Staphylococcus aureus: antibiotic susceptibility profile,
      resistance genes and molecular typing of methicillin-resistant and methicillin
      sensitive strains in China.
AB  - The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infection in
      dairy animals is of great concern for livestock and public health. The aim of
      present study was to detect new trends of methicillin-resistant Staphylococcus
      aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) towards
      antibiotic susceptibility, resistance genes and molecular typing by methods of
      disc diffusion, multiplex PCR assay and multilocus sequence typing (MLST). A
      total of 219 S. aureus strains were isolated from bovine mastitis cases from six
      provinces of China, including 34 MRSA strains. The results revealed that more
      than 70% isolated strains showed resistance to various antibiotics, and multiple
      drugs resistance to more than five categories of antibiotics was found more
      common. The ermC was the most prevalent resistance gene, followed by other genes;
      however, ermA was the least frequently detected gene. Twenty-eight mecA-negative
      MRSA and six mecA-positive MRSA strains were detected, and in which three strains
      were ST97-MRSA-IV, others were ST965-MRSA-IV, ST6-MRSA-IV and ST9-MRSA-SCCmec-NT.
      The mecA-negative MRSA strains were found resistant to most of the antibiotics,
      and harbored aac(6')/aph(2''), aph(3')-III and tetM genes higher than MSSA
      strains. The resistance to most of the antibiotics was significantly higher in
      MRSA than in MSSA strains. The MLST profiles showed that these strains mainly
      belonged to CC5, CC398, CC121 and CC50 lineage, especially within ST97 and ST398,
      while some novel sequence types (ST2154, ST2165 and ST2166) were identified and
      deposited in the MLST database. This indicates that the resistance of S. aureus
      is becoming more complicated by changes in multi-drug resistance mechanism and
      appearance of mecA-negative MRSA isolates, and importantly, MRSA-IV strains in
      different MLST types are emerging. 

PMID- 25582605
TI  - The avian pathogenic Escherichia coli O2 strain E058 carrying the defined
      aerobactin-defective iucD or iucDiutA mutation is less virulent in the chicken.
AB  - The expression of aerobactin accounts for much of the pathogenesis of avian
      pathogenic Escherichia coli (APEC). iucA, iucB, iucC and iucD are involved in
      aerobactin synthesis and iutA is responsible for the expression of a specific
      outer membrane receptor protein for ferric aerobactin. Knockout mutants of iucD
      and iucDiutA in the APEC O2 strain E058 were constructed and named E058DeltaiucD
      and E058DeltaiucDDeltaiutA, respectively. To evaluate the pathogenicity of these
      mutants, we used multiple approaches to assess the effects of mutations on the
      virulence of APEC E058. Aerobactin-defective mutants E058DeltaiucD and
      E058DeltaiucDDeltaiutA showed significantly decreased pathogenicity compared with
      the wild-type strain E058, evidenced by the low extent of colonization in
      selected organs or being outcompeted by E058 in vivo. Chickens challenged with
      APEC E058 exhibited typical signs and lesions of avian colibacillosis, while
      those inoculated with the mutants E058DeltaiucD or E058DeltaiucDDeltaiutA showed
      moderate airsacculitis, mild pericarditis and perihepatitis. However, no
      significant differences in resistance to specific-pathogen-free chicken serum,
      ingestion by HD-11 cells, and growth rates in LB were observed between the
      mutants and the wild-type strain. These results indicated that the IucD- and IutA
      related virulence factors play a significant role in the pathogenesis of the APEC
      strain E058. 

PMID- 25582606
TI  - Transformation of AgCl nanoparticles in a sewer system--A field study.
AB  - Silver nanoparticles (Ag-NP) are increasingly used in consumer products and their
      release during the use phase may negatively affect aquatic ecosystems. Research
      efforts, so far, have mainly addressed the application and use of metallic Ag(0)
      NP. However, as shown by recent studies on the release of Ag from textiles, other
      forms of Ag, especially silver chloride (AgCl), are released in much larger
      quantities than metallic Ag(0). In this field study, we report the release of
      AgCl-NP from a point source (industrial laundry that applied AgCl-NP during a
      piloting phase over a period of several months to protect textiles from bacterial
      regrowth) to the public sewer system and investigate the transformation of Ag
      during its transport in the sewer system and in the municipal wastewater
      treatment plant (WWTP). During the study period, the laundry discharged ~85 g of
      Ag per day, which dominated the Ag loads in the sewer system from the respective
      catchment (72-95%) and the Ag in the digested WWTP sludge (67%). Combined results
      from electron microscopy and X-ray absorption spectroscopy revealed that the Ag
      discharged from the laundry to the sewer consisted of about one third AgCl and
      two thirds Ag2S, both forms primarily occurring as nanoparticles with
      diameters<100 nm. During the 800 m transport in the sewer channel to the nearby
      WWTP, corresponding to a travel time of ~30 min, the remaining AgCl was
      transformed into nanoparticulate Ag2S. Ag2S-NP also dominated the Ag speciation
      in the digested sludge. In line with results from earlier studies, the very low
      Ag concentrations measured in the effluent of the WWTP (<0.5 MUg L(-1)) confirmed
      the very high removal efficiency of Ag from the wastewater stream (>95%).

PMID- 25582608
TI  - High incidence of interpersonal violence in Northwest Ethiopia: A cross-sectional
      study.
AB  - BACKGROUND: Interpersonal violence has devastating consequences for the mental,
      physical and sexual health of the victim. It is a leading cause of injury in east
      Africa. Studies in Ethiopia report that the most common cause of injury was
      interpersonal conflict. Our objective was to study the incidence of interpersonal
      violence related injury and associated factors among patients visiting the
      emergency department of University of Gondar Hospital, Northwest Ethiopia.
      METHODS: A cross-sectional institutional based study design was employed from
      November 2013-June 2014. The source population was a cohort sample of all
      patients presenting for treatment of a traumatic injury. Data were collected
      using injury surveillance guidelines developed by the World Health Organization.
      Bivariate and multivariate logistic regressions were performed to identify the
      presence and strength of association. Odds ratio with 95% confidence interval was
      computed to determine the level of significance. RESULTS: The overall incidence
      of interpersonal violence related injury was 28.5% of all emergency department
      trauma patients. Multivariate logistic regression shows that conflict in the
      family prior to the event [AOR = 9.9 (95% CI: 4.433-9.536)], poor behavioral
      control [AOR = 2.5 (95% CI: 1.192-5.460)], alcohol use [AOR =  .406 (95% CI:
      1.813-6.398)] and paternal education [AOR = 2.441(95% CI: 1.209-4.929)] were
      found to be independently associated with interpersonal violence related injury.
      CONCLUSION AND RECOMMENDATION: The incidence of interpersonal violence related
      injury was high. Counseling and education on conflict resolution methods should
      be given for the community using mass media.

PMID- 25582610
TI  - Highly efficient tetradentate ruthenium catalyst for ester reduction: especially
      for hydrogenation of fatty acid esters.
AB  - A new tetradentate ruthenium complex has been developed for hydrogenation of
      esters. The catalyst's structure features a pyridinemethanamino group and three
      tight chelating five-membered rings. The structure character is believed to be
      responsible for its high stability and high carbonylation-resistant properties.
      Thus, this catalyst shows outstanding performance in the catalytic hydrogenation
      of a variety of esters, especially for fatty acid esters, which may be used in
      practical applications. New insight on designing hydrogenation catalyst for
      reducing esters to alcohols has been provided through theoretical calculations. 

PMID- 25582609
TI  - Identification of six novel F9 mutations among haemophilia B patients from
      Macedonia and Bulgaria.

PMID- 25582607
TI  - Experiential reward learning outweighs instruction prior to adulthood.
AB  - Throughout our lives, we face the important task of distinguishing rewarding
      actions from those that are best avoided. Importantly, there are multiple means
      by which we acquire this information. Through trial and error, we use
      experiential feedback to evaluate our actions. We also learn which actions are
      advantageous through explicit instruction from others. Here, we examined whether
      the influence of these two forms of learning on choice changes across development
      by placing instruction and experience in competition in a probabilistic-learning
      task. Whereas inaccurate instruction markedly biased adults' estimations of a
      stimulus's value, children and adolescents were better able to objectively
      estimate stimulus values through experience. Instructional control of learning is
      thought to recruit prefrontal-striatal brain circuitry, which continues to mature
      into adulthood. Our behavioral data suggest that this protracted neurocognitive
      maturation may cause the motivated actions of children and adolescents to be less
      influenced by explicit instruction than are those of adults. This absence of a
      confirmation bias in children and adolescents represents a paradoxical
      developmental advantage of youth over adults in the unbiased evaluation of
      actions through positive and negative experience. 

PMID- 25582612
TI  - Organometallic polyphosphorus and -arsenic ligands as linkers between pre
      assembled linear Cu(I) fragments.
AB  - A simple and straightforward synthesis of a new linear trinuclear Cu(I) cluster
      with polyphosphine ligands is presented. The reaction of this pre-organized Cu3
      precursor with En ligand complexes (E = P, As; n = 2, 5) affords discrete
      complexes exhibiting end-on eta(1)-coordination of the E2 ligands or one
      dimensional coordination polymers featuring sigma-1,3-bridging E5 rings,
      respectively. 

PMID- 25582611
TI  - Intravenous lidocaine increases the depth of anaesthesia of propofol for skin
      incision--a randomised controlled trial.
AB  - BACKGROUND: The anaesthetic potency of intravenous propofol is quantified by its
      Cp50 value, which is defined as the plasma concentration required to prevent
      movement response in 50% of patients to surgical stimuli. We hypothesised that,
      in addition to propofol anaesthesia, an intravenous bolus of lidocaine 1.5 mg/kg
      will decrease the Cp50 value of propofol during anaesthesia. METHODS: We enrolled
      54 elective surgical patients undergoing propofol-based anaesthesia, and
      randomised them to either lidocaine 1.5 mg/kg, lidocaine 0.5 mg/kg or placebo
      (NaCl 0.9%) 3 min before skin incision. The propofol Cp50 value was then
      calculated using the 'up-and-down' method of Dixon and Massey. RESULTS: There was
      no significant reduction in propofol requirements after the administration of 0.5
      mg/kg lidocaine from 8.5 MUg/ml [confidence interval (CI) 6.0-11.625] to 8.25
      MUg/ml (CI 6.75-9.76); however, a bolus of 1.5 mg/kg lidocaine decreased the Cp50
      value of propofol by 42% from 8.5 MUg/ml (CI 6.0-11.625) to 4.92 MUg/ml (CI 4.5
      5.78) (P < 0.05). CONCLUSION: An intravenous bolus injection of 1.5 mg/kg
      lidocaine 2% caused a significant reduction of the propofol Cp50 value.

PMID- 25582613
TI  - Methicillin-resistant Staphylococcus aureus and extended-spectrum and AmpC beta
      lactamase-producing Escherichia coli in broilers and in people living and/or
      working on organic broiler farms.
AB  - The aim of this study was to estimate the prevalence of methicillin-resistant
      Staphylococcus aureus (MRSA) and extended-spectrum and AmpC beta-lactamase
      (ESBL/AmpC)-producing Escherichia coli among broilers, and humans living and/or
      working on organic broiler farms; further characterise isolates; and compare
      these results with those from conventional farms. In the Netherlands, only 9
      certified organic broiler farms were present. On 8 of these farms, 60 throat
      swabs and 20 cloacal swabs were taken per farm for MRSA and ESBL/AmpC-E. coli
      detection, respectively, at an average age of both 34 (T1) and 68 (T2) days.
      Faecal swabs and questionnaires were returned by 27 out of 36 humans. For
      selected ESBL/AmpC-producing E. coli isolates, phylogenetic groups, beta
      lactamase genes, plasmid families, and sequence types were determined. MRSA was
      not detected in broiler and human samples. ESBL/AmpC-producing E. coli were
      isolated from broilers on 7/8 farms at T1 and on all farms at T2. Furthermore, 3
      farmers at T1, and 2 farmers and 1 family member at T2 were positive. Genes found
      in broilers and humans were almost exclusively blaCTX-M-1 and blaCMY-2. Given the
      high overall human ESBL/AmpC-prevalence (18.5%), which is similar to conventional
      farms, contact with live broilers is assumed a risk factor for carriage. Farm and
      sample-level prevalence at T1 are consistent with those from conventional farms.
      At T2, just before slaughter, sample-level prevalence of ESBL/AmpC-E. coli
      appears to have decreased (94.3% vs. 80%), which could have important
      consequences for contamination of retail meat. 

PMID- 25582614
TI  - Equid herpesvirus 1 (EHV1) infection of equine mesenchymal stem cells induces a
      pUL56-dependent downregulation of select cell surface markers.
AB  - Equid herpesvirus 1 (EHV1) is an ubiquitous alphaherpesvirus that can cause
      respiratory disease, abortion and central nervous disorders. EHV1 is known to
      infect a variety of different cell types in vitro, but its tropism for cultured
      primary equine mesenchymal stem cells (MSC) has never been explored. We report
      that equine MSC were highly permissive for EHV1 and supported lytic replication
      of the virus in vitro. Interestingly, we observed that an infection of MSC with
      EHV1 resulted in a consistent downregulation of cell surface molecules CD29
      (beta1-integrin), CD105 (endoglin), major histocompatibility complex type I
      (MHCI) and a variable downregulation of CD172a. In contrast, expression of CD44
      and CD90 remained unchanged upon wild type infection. In addition, we found that
      this selective EHV1-mediated downregulation of cell surface proteins was
      dependent on the viral protein UL56 (pUL56). So far, pUL56-dependent
      downregulation during EHV1 infection of equine cells has only been described for
      MHCI, but our present data indicate that pUL56 may have a broader function in
      downregulating cell surface proteins. Taken together, our results are the first
      to show that equine MSC are susceptible for EHV1 and that pUL56 induces
      downregulation of several cell surface molecules on infected cells. These
      findings provide a basis for future studies to evaluate the mechanisms underlying
      for this selective pUL56-induced downregulation and to evaluate the potential
      role of MSC during EHV1 pathogenesis. 

PMID- 25582615
TI  - Generation of comparative pharmacophoric model for steroidal 5alpha-reductase I
      and II inhibitors: A 3D-QSAR study on 6-azasteroids.
AB  - Steroidal 5alpha-reductase, a key enzyme involved in the transformation of
      testosterone to dihydrotestosterone, is unstable during the purification leading
      to loss of the activity. Therefore, due to unstable nature, the crystal structure
      of the 5alpha-reductase is unknown. In the present study, we have generated a
      comparative pharmacophoric model for both isoforms of steroidal 5alpha-reductase
      using 6-azasteroids. The steric and electrostatic maps generated for both
      isoforms provides structure framework for designing of new inhibitors. Further,
      3D-maps are also helpful in understanding variability in the activity of the
      compounds. Statistical measures generated for both enzymes showed good internal
      and external prediction. Overall, the analyses of models provides structural
      requirement of dual and selective steroidal 5alpha-reductase inhibitors in an
      interactive fashion. 

PMID- 25582616
TI  - Altered mTORC1 signaling in multipotent stem cells from nearly 25% of patients
      with nonsyndromic autism spectrum disorders.

PMID- 25582617
TI  - Increased female autosomal burden of rare copy number variants in human
      populations and in autism families.
AB  - Autosomal genetic variation is presumed equivalent in males and females and makes
      a major contribution to disease risk. We set out to identify whether maternal
      copy number variants (CNVs) contribute to autism spectrum disorders (ASDs).
      Surprisingly, we observed a higher autosomal burden of large, rare CNVs in
      females in the population, reflected in, but not unique to, ASD families. Meta
      analysis across control data sets confirms female excess in CNV number (P=2.1 *
      10(-5)) and gene content (P=4.1 * 10(-3)). We additionally observed CNV
      enrichment in ASD mothers compared with control mothers (P=0.03). We speculate
      that tolerance for CNV burden contributes to decreased female fetal loss in the
      population and that ASD-specific maternal CNV burden may contribute to high
      sibling recurrence. These data emphasize the need for study of familial CNV risk
      factors in ASDs and the requirement of sex-matched comparisons. 

PMID- 25582619
TI  - Ligand orientation in a membrane-embedded receptor site revealed by solid-state
      NMR with paramagnetic relaxation enhancement.
AB  - NMR relaxation enhancement by paramagnetic metals provides powerful restraints on
      the three-dimensional structures of proteins in solution, and this approach has
      recently been utilized in several NMR structural investigations of proteins in
      the solid-state. Here we utilize paramagnetic relaxation enhancement (PRE) by
      Mn(2+) with cross-polarization magic-angle spinning (CP-MAS) solid-state NMR to
      investigate the interaction of a membrane-embedded protein the Na,K-ATPase (NKA)
      with a cardiotonic steroid inhibitor. The inhibitor, a diacetonide derivate of
      the cardiac glycoside ouabain, with (13)C labelled acetonide groups in the
      rhamnose sugar and steroid moieties ([(13)C2]ODA), is 1000-fold less potent than
      the parent compound. It is shown that the (13)C CP-MAS solid-state NMR spectra of
      the NKA-[(13)C2]ODA complex exhibit distinct signals for the two (13)C labels of
      the inhibitor when bound to the ouabain site of membrane-embedded NKA. Recent
      crystal structures of NKA indicate that the catalytic alpha-subunit binds a
      single Mn(2+) in a transmembrane site close to the high-affinity ouabain site.
      Here, complexation of NKA with Mn(2+) broadens the resonance line from the
      rhamnose group substantially more than the steroid peak, indicating that the
      rhamnose group is closer to the Mn(2+) site than is the steroid group. These
      observations agree with computational molecular docking simulations and are
      consistent with ODA adopting an inverted orientation compared to ouabain in the
      cardiac glycoside site, with the modified rhamnose group drawn toward the
      transmembrane centre of the protein. This work demonstrates that PRE can provide
      unique information on the positions and orientations of ligands within their
      binding pockets of transmembrane proteins. 

PMID- 25582618
TI  - Psychiatric blood biomarkers: avoiding jumping to premature negative or positive
      conclusions.
AB  - Blood biomarkers may provide a scientifically useful and clinically usable
      peripheral signal in psychiatry, as they have been doing for other fields of
      medicine. Jumping to premature conclusions, negative or positive, can create
      confusion in this field. Reproducibility is a hallmark of good science. We
      discuss some recent examples from this dynamic field, and show some new data in
      support of previously published biomarkers for suicidality (SAT1, MARCKS and
      SKA2). Methodological clarity and rigor in terms of biomarker discovery,
      validation and testing is needed. We propose a set of principles for what
      constitutes a good biomarker, similar in spirit to the Koch postulates used at
      the birth of the field of infectious diseases. 

PMID- 25582620
TI  - Is there an optimal location for tympanostomy tube placement?

PMID- 25582621
TI  - 'It Takes Me Half a Bottle of Whisky to Get through One of Your Assignments':
      Exploring One Teacher Educator's Personal Experiences of Dyslexia.
AB  - This article uses a life history approach to explore personal experiences of
      dyslexia of one higher-education lecturer and its impact on her professional
      identity. The informant is currently employed as a lecturer of initial teacher
      training in a UK university. She worked as a primary school teacher for over a
      decade prior to embarking on an academic career in teacher education. The
      informant draws on her own experiences as a pupil, teacher and lecturer, and
      additionally, she presents accounts of student teachers with dyslexia drawn from
      her current professional context. Although the data are not generalizable, the
      account nevertheless illustrates the positive impact of the social model of
      disability for the informant and her students who had been identified as dyslexic
      during their initial training as teachers. Additionally, the account also
      illustrates the ways in which teachers' personal experiences of dyslexia can
      shape professional identities in very positive ways. Implications for both
      teacher training and pedagogic approaches in schools to support learners with
      dyslexia are drawn out of the narrative.

PMID- 25582623
TI  - Glucose-dependent insulinotropic polypeptide (GIP) directly affects collagen
      fibril diameter and collagen cross-linking in osteoblast cultures.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is absolutely crucial in order
      to obtain optimal bone strength and collagen quality. However, as the GIPR is
      expressed in several tissues other than bone, it is difficult to ascertain
      whether the observed modifications of collagen maturity, reported in animal
      studies, were due to direct effects on osteoblasts or indirect through regulation
      of signals originating from other tissues. The aims of the present study were to
      investigate whether GIP can directly affect collagen biosynthesis and processing
      in osteoblast cultures and to decipher which molecular pathways were necessary
      for such effects. MC3T3-E1 cells were cultured in the presence of GIP ranged
      between 10 and 100pM. Collagen fibril diameter was investigated by electron
      microscopy whilst collagen maturity was determined by Fourier transform infra-red
      microspectroscopy (FTIRM). GIP treatment resulted in dose-dependent increases in
      lysyl oxidase activity and collagen maturity. Furthermore, GIP treatment shifted
      the collagen fiber diameter towards lower value but did not significantly affect
      collagen heterogeneity. GIP acted directly on osteoblasts by activating the
      adenylyl cyclase-cAMP pathway. This study provides evidences that GIP acts
      directly on osteoblasts and is capable of improving collagen maturity and fibril
      diameter. 

PMID- 25582622
TI  - Ophiopogonin D: A new herbal agent against osteoporosis.
AB  - Excessive reactive oxygen species (ROS) play an important role in the development
      of osteoporosis. Ophiopogonin D (OP-D), isolated from the traditional Chinese
      herbal agent Radix Ophiopogon japonicus, is a potent anti-oxidative agent. We
      hypothesized that OP-D demonstrates anti-osteoporosis effects via decreasing ROS
      generation in mouse pre-osteoblast cell line MC3T3-E1 subclone 4 cells and a
      macrophage cell line RAW264.7 cells. We investigated OP-D on osteogenic and
      osteoclastic differentiation under oxidative status. Hydrogen peroxide (H2O2) was
      used to establish an oxidative damage model. In vivo, we established a murine
      ovariectomized (OVX) osteoporosis model. Then, we searched the molecular
      mechanism of OP-D against osteoporosis. Our results revealed that OP-D
      significantly promoted the proliferation of MC3T3-E1 cells and improved some
      osteogenic markers. Moreover, OP-D reduced TRAP activity and the mRNA expressions
      of osteoclastic genes in RAW264.7 cells. OP-D suppressed ROS generation in both
      MC3T3-E1 and RAW264.7 cells. OP-D treatment reduced the activity of serum bone
      degradation markers, including CTX-1 and TRAP. Further research showed that OP-D
      displayed anti-osteoporosis effects via reducing ROS through the FoxO3a-beta
      catenin signaling pathway. In summary, our results indicated that the protective
      effects of OP-D against osteoporosis are linked to a reduction in oxidative
      stress via the FoxO3a-beta-catenin signaling pathway, suggesting that OP-D may be
      a beneficial herbal agent in bone-related disorders, such as osteoporosis. 

PMID- 25582624
TI  - Racial parity in tumor burden, treatment choice and survival outcomes in men with
      prostate cancer in the VA healthcare system.
AB  - BACKGROUND: African-American men with prostate cancer typically have higher tumor
      risk at diagnosis, lower rates of surgical treatment and poorer cancer-specific
      survival compared with Caucasians. Receipt of care within the Veterans Affairs
      (VA) healthcare system may reduce barriers that influence these disparities.
      METHODS: We sampled 1258 men with nonmetastatic prostate cancer diagnosed at the
      Greater Los Angeles and Long Beach VA Medical Centers between 1998 and 2004. We
      compared African Americans and Caucasians with respect to tumor characteristics
      using ordinal logistic regression, treatment choice across substrata of tumor
      risk using logistic regression, and cancer-specific and other-cause mortality
      using competing risks regression analysis. RESULTS: Multivariate ordinal logistic
      regression revealed no significant differences in odds of higher tumor risk (odds
      ratio (OR) 1.22, 95% confidence interval (CI) 0.98-1.53, P=0.08), Gleason score
      (OR 0.90, 95% CI 0.7-1.16, P=0.4) or clinical stage (OR 1.04, 95% CI 0.79-1.38,
      P=0.8) for African Americans compared with Caucasians. African-American men had
      similar odds of aggressive treatment as did Caucasians for low-risk (OR 0.92, 95%
      CI 0.57-1.53, P=0.8), intermediate-risk (OR 0.75, 95% CI 0.44-1.26, P=0.3) and
      high-risk disease (OR 0.87, 95% CI 0.52-1.44, P=0.6). In competing risks
      regression analysis, African Americans had a lower but nonsignificant hazard of
      cancer-specific mortality compared with Caucasians (sub-hazard ratio 0.6, 95% CI
      0.28-1.26, P=0.2) and nearly identical risk of other-cause mortality (sub-hazard
      ratio 0.98, 95% CI 0.78-1.22, P=0.8). CONCLUSIONS: We found no significant
      differences in tumor burden, treatment choice or survival outcomes between
      African Americans and Caucasians cared for in the equal-access VA Healthcare
      setting.

PMID- 25582625
TI  - The Role of Macrophages in Promoting and Maintaining Homeostasis at the Fetal
      Maternal Interface.
AB  - A successful pregnancy requires that the maternal immune system adapts properly
      to avoid rejection of the semi-allogeneic fetus without compromising the ability
      to protect the mother and the fetus against infections. In this review, we
      describe the role of decidual macrophages in creating a homeostatic environment
      at the fetal-maternal interface. We also discuss their role in pregnancy
      complications as well as future possibilities to modulate macrophage function
      therapeutically. Decidual macrophages are enriched at the fetal-maternal
      interface and play a major role in the regulation of inflammatory responses and
      the maintenance of a tolerant environment. Their function is, however, not
      restricted to immune tolerance, but extends to include functions such as the
      recognition and clearance of infections, the clearance of apoptotic debris, and
      tissue remodeling. Decidual macrophages seem to largely function as tissue
      resident macrophages that are crucial for maintaining homeostasis and
      reproductive success. 

PMID- 25582626
TI  - First-principles study of electronic structure and photocatalytic properties of
      MnNiO3 as an alkaline oxygen-evolution photocatalyst.
AB  - We present a first-principles study of MnNiO3, a promising oxygen-evolution
      photocatalyst. Using density functional theory with the PBE + U functional and
      the screened hybrid functional of Heyd, Scuseria, and Ernzerhof (HSE), we compute
      and analyze the ground-state geometry and electronic structure. We find that
      MnNiO3 is a ferrimagnetic semiconductor with an indirect band gap, consistent
      with experimental observations. We also predict that MnNiO3 has promising band
      edge positions relative to the vacuum, with potential to straddle the hydrogen
      evolution reaction (HER) and oxygen evolution reaction (OER) redox potentials in
      aqueous solution. A detailed analysis of the band structure and density of states
      provides a clear explanation for why MnNiO3 has appropriate electronic properties
      for OER. Furthermore, comprehensive calculations of its Pourbaix diagram suggest
      that MnNiO3 is stable in alkaline solution at potentials relevant for oxygen
      evolution. 

PMID- 25582628
TI  - EFIS turns 40!

PMID- 25582634
TI  - Effectiveness of multiple sclerosis treatment with current immunomodulatory
      drugs.
AB  - INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the
      CNS of a putative autoimmune origin characterized by neurologic dysfunction
      disseminated in space and time due to demyelination and axonal loss that results
      in progressive disability. Recent advances in understanding the immune
      pathogenesis of the disease resulted in the introduction of numerous effective
      immunomodulatoty drugs having diverse mechanisms of action, modes of
      administration and risk-benefit profiles. This results in more complex albeit
      more promising treatment selection and choices. AREAS COVERED: The epidemiology,
      clinical features, pathogenesis and diagnosis of the disease are discussed. The
      mode of action and main characteristics of current immunomodulatory drugs for MS
      and their place in the therapeutic algorithm of the disease based on evidence
      from clinical trials are described. Speculation on new paradigms, treatment goals
      and outcome measures aimed at improving the landscape of MS treatment is
      presented. EXPERT OPINION: Multiple disease, drug and patient-related factors
      should be taken into consideration when selecting the appropriate drug and
      treatment strategy to the appropriate patient, thus paving the road for
      personalized medicine in MS.

PMID- 25582635
TI  - Blood reflects tissue oxidative stress: a systematic review.
AB  - We examined whether the levels of oxidative stress biomarkers measured in blood
      reflect the tissue redox status. Data from studies that measured redox biomarkers
      in blood, heart, liver, kidney and skeletal muscle were analyzed. In seven out of
      nine investigated redox biomarkers (malondialdehyde, reduced glutathione,
      superoxide dismutase, catalase, glutathione peroxidase, vitamin C and E) there
      was generally good qualitative and quantitative agreement between the blood and
      tissues. In contrast, oxidized glutathione and the reduced to oxidized
      glutathione ratio showed poor agreement between the blood and tissues. This study
      suggests that most redox biomarkers measured in blood adequately reflect tissue
      redox status. 

PMID- 25582636
TI  - Intestinal temperature does not reflect rectal temperature during prolonged,
      intense running with cold fluid ingestion.
AB  - It is generally assumed that intestinal temperature (Tint), as measured with a
      telemetric pill, agrees relatively well with rectal temperature (Trec) during
      exercise. However, whether Tint reflects Trec during prolonged, intense and
      continuous exercise when cold fluids are consumed is unknown. Therefore, we
      compared Trec and Tint during a half-marathon during which cold water was
      ingested to prevent bodyweight (BW) losses >2%. Nine endurance athletes (age 30 
      +/-  5 years) underwent a 21.1 km running time-trial (TT) in the heat (~30 
      degrees C and 44% RH) while BW losses were maintained to ~1% with continuous cold
      (4  degrees C) water provision. Tint and Trec were monitored throughout the TT.
      Hypohydration level, TT time and fluid intake were 1.2  +/-  0.4% BW, 93.2  +/- 
      9.9 min and 2143  +/-  264 ml, respectively. Trec was systematically higher than
      Tint by 0.25  degrees C (95% CI: 0.14-0.37  degrees C). Tint and Trec showed an
      excellent relative (r = 0.90, p < 0.01), but poor absolute agreement as reflected
      by a 95% limit of agreement of +/-1.07  degrees C and a standard error of
      measurement of +/-0.39  degrees C. In conclusion, Tint does not mirror Trec
      during prolonged, intense running with cold fluid ingestion and, therefore, these
      measures should not be used interchangeably under this scenario.

PMID- 25582637
TI  - School-Based Obesity Intervention Associated with Three Year Decrease in Student
      Weight Status in a Low-Income School District.
AB  - School-based interventions may be a way to address increasing rates of childhood
      obesity. Following an obesity intervention implemented by a low-income school
      district we found evidence of weight status change among district students. The
      school district served 5,000 children in Western New York at that time and
      approximately 4,000 students were in the target group (grades 3-12). The district
      allocated federal grant funds to implement changes to physical education
      equipment and curriculum, health education curriculum, and school food and to
      offer afterschool access to equipment and activities. As part of the grant
      reporting requirements, school staff measured student height and weight twice
      yearly for three years. We were subcontracted as evaluators for this grant and
      district staff shared this de-identified data with us for assistance with grant
      reporting. We obtained IRB approval from SUNY at Buffalo for analysis and
      publication of the data. Data analysis involved longitudinal descriptive and
      inferential (paired-samples t tests, Chi square tests) statistical analyses of
      Body Mass Index (BMI) percentiles of students with baseline and endpoint height
      and weight measurements (n = 2,259). Overall the mean BMI percentile of students
      decreased significantly from 70.4 to 65.7% (p < 0.001). This exceeds the change
      in BMI percentile seen at the national level. There was a significant decrease in
      the proportion of students categorized as overweight or obese (p < 0.001).
      Conclusions are limited due to the lack of a control population however they
      indicate that a three year multilevel school-based intervention involving
      physical activity and nutritional changes was correlated with improved weight
      status among participating school children.

PMID- 25582638
TI  - Human health-related ecosystem services of avian-dense coastal wetlands adjacent
      to a Western Lake Erie swimming beach.
AB  - Wetlands provide many valuable ecosystem services, including water quality
      improvement to protect downstream aquatic ecosystems such as lakes, rivers, and
      estuaries. However, their ability to improve water quality to safe levels for
      direct human exposure while largely surrounded by agricultural lands and hosting
      large wildlife populations remains unknown. Our aim was to examine the ecosystem
      service capabilities of an avian-dense coastal wetland surrounded by agricultural
      lands along the southwestern shore of Lake Erie in Ohio by assessing the quality
      of water as it flows through the wetland (Ottawa National Wildlife Refuge (ONWR))
      and into Lake Erie beach waters. Our study used total phosphorus and fecal
      indicator (Escherichia coli) concentrations as water quality metrics across the
      wetland and at an adjacent Lake Erie swimming beach during the 2012 summer swim
      season. E. coli and total P levels were consistently highest at the site, where
      water enters the ONWR (mean E. coli = 507 CFU/100 mL; mean total P = 535 MUg/L),
      and steadily decreased as water flowed through the wetland and into the adjacent
      beach (mean E. coli = 10 CFU/100 mL; mean total P = 41 MUg/L). E. coli and total
      P showed statistically significant (alpha = 0.01) correlations with phycocyanin,
      chlorophyll-a, turbidity, specific conductivity, dissolved oxygen, and pH; total
      P was also significantly correlated with total N. The results suggest that this
      wetland may be contributing to improving water quality, which is beneficial for
      human health as well as to downstream ecosystem health (e.g., limiting
      eutrophication promoting conditions, etc.).

PMID- 25582639
TI  - Development and validation of the Occupational Therapy Risk Propensity Test (OT
      RiPT) for drivers with disability.
AB  - BACKGROUND: Male drivers in the 16- to 19-year age group have a nine-fold
      increase in their crash risk compared with 25- to 34-year-olds who have a
      relative risk of 2.3. Crash risk in young drivers has been directly linked to
      risk-taking behaviour. This paper reports the development of a video risk
      assessment tool for use with drivers. AIM/OBJECTIVE: This paper reports on the
      process of validating and investigating the reliability of the Occupational
      Therapy Risk Propensity Test (OT-RiPT) to measure risk-taking propensity.
      MATERIAL AND METHODS: 20 healthy male participants were recruited. OT-RiPT scores
      were correlated with driving experience. Internal consistency was investigated
      using Cronbach's alpha. Face validity was established. The OT-RiPT and a
      validated driver behaviour questionnaire were administered and the results
      correlated to establish discriminant validity. RESULTS: There was no significant
      correlation between driving experience and OT-RiPT scores. Good internal
      consistency was established. OT-RiPT has high face validity. Discriminant
      validity was demonstrated. CONCLUSION AND SIGNIFICANCE: Pending further testing,
      OT-RiPT shows promise as a reliable and valid measure of risk-taking propensity
      in young drivers.

PMID- 25582640
TI  - Mucosal-sparing posterior septectomy for endoscopic endonasal approach to the
      craniocervical junction.
AB  - Recent technological advances and developments in surgical technique have made
      the craniocervical junction (CCJ) accessible through the transnasal surgical
      corridor. Endoscopic endonasal transclival and transodontoid approaches have been
      previously described in the literature. Traditionally, these approaches entail a
      posterior bony and mucosal septectomy. This posterior bony and mucosal septectomy
      can compromise the integrity of the posterior septum and damage the vascularized
      pedicled nasoseptal flap (PNSF), a robust reconstructive option. With the
      possibility of an intraoperative cerebrospinal fluid (CSF) leak and the reported
      success of the PNSF for repair of these defects, preserving the integrity of the
      PNSF is beneficial during the endoscopic endonasal approach to the CCJ. Here, we
      present a new variation which preserves the mucosal integrity of the posterior
      nasal septum and PNSF. This mucosal-sparing variation of the traditional
      endoscopic endonasal transclival and transodontoid approaches allows for the
      preservation of posterior mucosal nasoseptal integrity, and salvages a
      reconstructive option for future usage. This is accomplished at no expense to
      visualization, surgical access, or maneuverability. 

PMID- 25582641
TI  - Radiotherapy of osseous echinococcosis: where is the evidence?

PMID- 25582642
TI  - Artificial neural networks to model the production of blood protein hydrolysates
      for plant fertilisation.
AB  - BACKGROUND: Amino acid-based fertilisers increase the bioavailability of nitrogen
      in plants and help withstand stress conditions. Additionally, porcine blood
      protein hydrolysates are able to supply iron, which is involved in chlorophyll
      synthesis and improves the availability of nutrients in soil. A high degree of
      hydrolysis is desirable when producing a protein hydrolysate intended for
      fertilisation, since it assures a high supply of free amino acids. Given the
      complexity of enzyme reactions, empirical approaches such as artificial neural
      networks (ANNs) are preferred for modelisation. RESULTS: Porcine blood meal was
      hydrolysed for 3 h with subtilisin. The time evolution of the degree of
      hydrolysis was successfully modelled by means of a feedforward ANN comprising 10
      neurons in the hidden layer and trained by the Levenberg-Marquardt algorithm. The
      ANN model described adequately the influence of pH, temperature, enzyme
      concentration and reaction time upon the degree of hydrolysis, and was used to
      estimate the optimal operation conditions (pH 6.67, 56.9  degrees C, enzyme to
      substrate ratio of 10 g kg(-1) and 3 h of reaction) leading to the maximum degree
      of hydrolysis (35.12%). CONCLUSIONS: ANN modelling was a useful tool to model
      enzymatic reactions and was successfully employed to optimise the degree of
      hydrolysis.

PMID- 25582644
TI  - Predictive values of models of Clostridium difficile infection.
AB  - In vivo and in vitro models are widely used to simulate Clostridium difficile
      infection (CDI). They have made considerable contributions in the study of C
      difficile pathogenesis, antibiotic predisposition to CDI, and population dynamics
      as well as the evaluation of new antimicrobial and immunologic therapeutics.
      Although CDI models have greatly increased understanding of this complicated
      pathogen, all have limitations in reproducing human disease, notably their
      inability to generate a truly reflective immune response. This review summarizes
      the most commonly used models of CDI and discusses their pros and cons and their
      predictive values in terms of clinical outcomes.

PMID- 25582645
TI  - The contribution of strains and hosts to outcomes in Clostridium difficile
      infection.
AB  - Acquisition of Clostridium difficile spores can be followed by a spectrum of
      clinical outcomes ranging from asymptomatic transit through the bowel to severe
      colitis and death. This clinical variability is a product of bacterial virulence
      and host susceptibility to the pathogen. It is important to identify patients at
      high risk of poor outcome so that increased monitoring and optimal treatment
      strategies can be instigated. This article discusses the evidence linking strain
      type to clinical outcome, including the importance of toxin and nontoxin
      virulence factors. It reviews host factors and their relationship with C
      difficile infection susceptibility, recurrence, and mortality. 

PMID- 25582646
TI  - Potential sources of Clostridium difficile in human infection.
AB  - The view of Clostridium difficile infection as a hospital-acquired infection
      transmitted only by symptomatic patients is changing. Although C difficile is
      present in food for human consumption, food-borne infection caused by C difficile
      has never been confirmed. More information on the infective dose and the level of
      contamination is needed to determine the risk for food-borne exposure to C
      difficile in humans. The emergence of C difficile polymerase chain reaction (PCR)
      ribotype 078 in humans is epidemiologically linked to its presence in piglets and
      calves and their environment, suggesting zoonotic transmission. 

PMID- 25582647
TI  - The epidemiology of Clostridium difficile infection inside and outside health
      care institutions.
AB  - This article describes the global changes in Clostridium difficile epidemiology
      since the late twentieth century and into the twenty-first century when the new
      epidemic strain BI/NAP1/027 emerged. The article provides an overview of how
      understanding of C difficile epidemiology has rapidly evolved since its initial
      association with colitis in 1974. It also discusses how C difficile has spread
      across the globe, the role of asymptomatic carriers in disease transmission, the
      increased recognition of C difficile outside health care settings, the changes in
      epidemiology of C difficile infection in children, and the risk factors for
      disease. 

PMID- 25582643
TI  - Crosstalk between advanced glycation end products (AGEs)-receptor RAGE axis and
      dipeptidyl peptidase-4-incretin system in diabetic vascular complications.
AB  - Advanced glycation end products (AGEs) consist of heterogenous group of
      macroprotein derivatives, which are formed by non-enzymatic reaction between
      reducing sugars and amino groups of proteins, lipids and nucleic acids, and whose
      process has progressed at an accelerated rate under diabetes. Non-enzymatic
      glycation and cross-linking of protein alter its structural integrity and
      function, contributing to the aging of macromolecules. Furthermore, engagement of
      receptor for AGEs (RAGE) with AGEs elicits oxidative stress generation and
      subsequently evokes proliferative, inflammatory, and fibrotic reactions in a
      variety of cells. Indeed, accumulating evidence has suggested the active
      involvement of accumulation of AGEs in diabetes-associated disorders such as
      diabetic microangiopathy, atherosclerotic cardiovascular diseases, Alzheimer's
      disease and osteoporosis. Glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) are incretins, gut hormones secreted from the
      intestine in response to food intake, both of which augment glucose-induced
      insulin release, suppress glucagon secretion, and slow gastric emptying. Since
      GLP-1 and GIP are rapidly degraded and inactivated by dipeptidyl peptidase-4 (DPP
      4), inhibition of DPP-4 and/or DPP-4-resistant GLP-1 analogues have been proposed
      as a potential target for the treatment of diabetes. Recently, DPP-4 has been
      shown to cleave multiple peptides, and blockade of DPP-4 could exert diverse
      biological actions in GLP-1- or GIP-independent manner. This article summarizes
      the crosstalk between AGEs-RAGE axis and DPP-4-incretin system in the development
      and progression of diabetes-associated disorders and its therapeutic
      intervention, especially focusing on diabetic vascular complications. 

PMID- 25582648
TI  - Combined bilateral femoral head necrosis and pertrochanteric fracture: a case
      report.
AB  - INTRODUCTION: Modular femoral implants have become a regular feature of revision
      hip surgery. However, for a primary hip arthroplasty, such as a femoral neck
      fracture case, the implant of choice is a standard femoral component, while
      compelling literature evidence have made osteosynthesis the standard procedure
      for the vast majority of trochanteric fractures. CASE PRESENTATION: We present
      the case of a 66-year-old Caucasian woman presenting with two trochanteric
      fractures associated with primary and secondary hip osteoarthritis that were
      treated with an uncemented total hip replacement with a modular femoral
      component. CONCLUSIONS: We found that a modular femoral component can address the
      issues of stability and, in our case, proved to be a viable solution for treating
      cases that are complicated by concomitant acetabular or femoral head and neck
      pathology.

PMID- 25582649
TI  - Gastric mucosal lacerations in drowning: resuscitation artifact or sign of death
      by drowning ("Sehrt's sign")?

PMID- 25582650
TI  - Triglyceride to high-density lipoprotein cholesterol ratio and carotid intima
      medial thickness in Chinese adolescents with newly diagnosed type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To investigate the relationship between triglyceride to high-density
      lipoprotein cholesterol (TG/HDL-C) ratio and carotid intima-medial thickness
      (CIMT) in Chinese youth and adolescents with newly diagnosed type 2 diabetes
      mellitus (T2DM). METHODS: Ninety-eight subjects aged 10-24 yr with newly
      diagnosed T2DM had general inflammation, anthropometric, laboratory and CIMT data
      collected, and were divided into three groups based on TG/HDL-C tertiles.
      RESULTS: There were no significant differences in gender, age, fasting plasma
      glucose (FPG), hemoglobin A1c (HbA1c), and carotid arterial diameter (CAD) among
      the groups based on TG/HDL-C tertiles. Across TG/HDL-C tertiles, there was a
      significant progressive increase in body mass index (BMI), systolic blood
      pressure (SBP), diastolic blood pressure (DBP), homeostasis model assessment
      estimated insulin resistance (HOMA-IR), TG, total cholesterol (TC), low-density
      lipoprotein-cholesterol (LDL-C) and CIMT (all P < 0.01 or P < 0.05), while HDL-C
      was decreased significantly across the groups (P < 0.01). In general linear
      regression model, TG/HDL-C was an independent determinant of CIMT even after
      adjusting for BMI, SBP, DBP, TG, TC, LDL-C, HDL-C, HbA1c and HOMA-IR. CONCLUSION:
      TG/HDL-C ratio, the marker of small dense LDL particles, is an independent
      determinant of CIMT in Chinese youth and adolescents with newly diagnosed T2DM,
      and may be a simple and helpful tool in predicting the increased CIMT in such
      patients.

PMID- 25582652
TI  - Contact allergy induced by bisphenol A diglycidyl ether leachables from aluminium
      tubes for pharmaceutical use.
AB  - BACKGROUND: Aluminium tubes for pharmaceutical use are internally lacquered with
      epoxy resins (ER) based on bisphenol A diglycidyl ether (BADGE). Recently, it was
      shown that remnants of ER polymerization like BADGE are extractable from epoxy
      based coatings of commercially available tubes and may leach into semi-solid drug
      preparations. We aimed to evaluate the safety of BADGE-contaminated macrogol
      ointments in individuals sensitized to ER based on BADGE by use tests. METHODS:
      Repeated open application testing (ROAT) in 11 patients sensitized to ER based on
      BADGE with BADGE in macrogol ointments (3 mg/kg; 30 mg/kg, equivalent to BADGE
      concentration determined in macrogol ointment after storage in a commercially
      available tube; 300 mg/kg). RESULTS: The 30 mg/kg BADGE ointment elicited
      reactions in three patients, and another three patients reacted to 300 mg/kg
      BADGE ointment. No reactions to the vehicle control and 3 mg/kg BADGE were
      observed. CONCLUSIONS: Elevated BADGE concentrations in ER-coated aluminium tubes
      pose a risk of developing contact dermatitis to patients sensitized to ER based
      on BADGE. Quality standards are deemed necessary for the production of ER-coated
      aluminium tubes intended for pharmaceutical use and should consider the results
      of the present ROAT study.

PMID- 25582653
TI  - Are decreased AdipoR1 mRNA levels associated with adiponectin resistance in
      coronary artery disease patients?
AB  - The aim of the present study was to investigate if circulating adiponectin levels
      and the expression of AdipoR1 and AdipoR2 in peripheral blood mononuclear cells
      (PBMC) are altered in coronary artery disease (CAD) patients, with and without
      significant stenosis, compared to healthy patients. The present study included 69
      patients with presenting symptoms of CAD (26 patients with significant stenosis
      and 43 patients without significant stenosis). The control group (CG) consisted
      of 33 healthy patients. Circulating adiponectin levels were measured by enzyme
      linked immunosorbent assay, whereas AdipoR1 and AdipoR2 mRNA levels in PBMC were
      determined by real-time polymerase chain reaction. Adiponectin levels were
      significantly higher in patients with and without significant stenosis compared
      to the CG (P < 0.001 vs P = 0.006, respectively). Both patient groups had lower
      AdipoR1 levels compared to the CG (P < 0.001 vs P < 0.001, respectively). There
      were no significant differences in these parameters between the two patient
      groups. Adiponectin negatively correlated with body mass index, triglycerides,
      insulin and homeostasis model assessment of insulin resistance index (HOMA IR),
      and positively with high-denisty lipoprotein cholesterol in the CG. Glucose,
      insulin, and the HOMA IR index negatively correlated with adiponectin in
      patients. A positive correlation between adiponectin receptors was found in
      patients and the CG. Decreased AdipoR1 mRNA levels and increased circulating
      adiponectin in advanced stages of CAD, as well as in patients without significant
      stenosis, compared to the CG, implies that CAD could be related to 'adiponectin
      resistance'. Despite increased adiponectin, its protective effects could be
      diminished even in early stages of atherosclerosis.

PMID- 25582654
TI  - Greenhouse gas mitigation on marginal land: a quantitative review of the relative
      benefits of forest recovery versus biofuel production.
AB  - Decisions concerning future land-use/land cover change stand at the forefront of
      ongoing debates on how to best mitigate climate change. In this study, we compare
      the greenhouse gas (GHG) mitigation value over a 30-year time frame for a range
      of forest recovery and biofuel production scenarios on abandoned agricultural
      land. Carbon sequestration in recovering forests is estimated based on a
      statistical analysis of tropical and temperate studies on marginal land. GHGs
      offset by biofuel production are analyzed for five different production pathways.
      We find that forest recovery is superior to low-yielding biofuel production
      scenarios such as oil palm and corn. Biofuel production scenarios with high
      yields, such as sugarcane or high-yielding energy grasses, can be comparable or
      superior to natural forest succession and to reforestation in some cases. This
      result stands in contrast to previous research suggesting that restoring degraded
      ecosystems to their native state is generally superior to agricultural production
      in terms of GHG mitigation. Further work is needed on carbon stock changes in
      forests, soil carbon dynamics, and bioenergy crop production on
      degraded/abandoned agricultural land. This finding also emphasizes the need to
      consider the full range of social, economic, and ecological consequences of land
      use policies. 

PMID- 25582655
TI  - Unrecognised myocardial infarction in patients with schizophrenia.
AB  - OBJECTIVE: Schizophrenia is associated with a reduction of the lifespan by 20
      years, with type II diabetes and cardiovascular disease contributing the most to
      the increased mortality. Unrecognised or silent myocardial infarction (MI) occurs
      in ~30% of the population, but the rates of unrecognised MI in patients with
      schizophrenia have only been sparsely investigated. METHOD: Electrocardiograms
      (ECG) from three psychiatric hospitals in Denmark were manually interpreted for
      signs of previous MI. Subsequently, ECGs were linked to the National Patient
      Registry in order to determine whether patients had a diagnosis consistent with
      previous MI. RESULTS: A total of 937 ECGs were interpreted, 538 men (57.4%) and
      399 women (42.6%). Mean age at the time of ECG acquisition was 40.6 years (95%
      CI: 39.7-41.5, range: 15.9-94.6). We identified 32 patients with positive ECG
      signs of MIs. Only two of these patients had a diagnosis of MI in the National
      Patient Registry. An additional number of eight patients had a diagnosis of MI in
      the Danish National Patient Registry, but with no ECG signs of previous MI. This
      means that 30 out of 40 (75%) MIs were unrecognised. Only increasing age was
      associated with unrecognised MI in a stepwise multiple logistic regression model
      compared with patients with no history of MI, OR: 1.03 per year of age, 95% CI:
      1.00-1.06, p=0.021. CONCLUSION: Unrecognised MI is common among patients with
      schizophrenia and may contribute to the increased mortality found in this patient
      group.

PMID- 25582656
TI  - Tungsten oxide single crystal nanosheets for enhanced multichannel solar light
      harvesting.
AB  - Substoichiometric tungsten oxide single-crystal nanosheets are successfully
      prepared via the exfoliation of layered tungstic acid and subsequent introduction
      of oxygen vacancies. The combination of different strategies, i.e., 2D-structure
      construction, the introduction of surface oxygen vacancies, and the creation of
      localized surface plasmon resonance can promote the light-harvesting performance
      of tungsten oxide through accumulative and synergistic effects. 

PMID- 25582657
TI  - Sporadic nonampullary duodenal adenoma/carcinoma is associated with not only
      colon adenoma/carcinoma but also gastric cancer: association of location of
      duodenal lesions with comorbid diseases.
AB  - BACKGROUND: It is well known that in patients with sporadic nonampullary duodenal
      adenoma/carcinoma (SNADA) with no polyposis syndrome, including familial
      adenomataous polyposis, the rates of colorectal adenoma/carcinoma are high.
      However, the prevalence rates of other tumor types, for example, gastric cancer,
      in SNADA patients remain unknown. In this study, we aimed to analyze the
      prevalence rate of comorbid diseases in SNADA patients. METHODS: We
      retrospectively analyzed 78 patients with SNADA treated by endoscopic resection
      between May 2005 and September 2014 at our institution. RESULTS: Overall, 51 of
      the 78 (65.4%) SNADA patients had comorbid colorectal adenoma/carcinoma. Further,
      10 of the 78 (12.8%) SNADA patients had comorbid gastric cancer, and all of them
      were positive for Helicobacter pylori infection. SNADA lesions were located
      significantly more frequently at the oral side of the major papilla in patients
      with H. pylori infection than in those without H. pylori infection (27 of 36
      [75.0%] vs. 19 of 42 [45.2%], p = 0.008, chi-square test). In contrast, SNADA
      lesions were located significantly more frequently at the anal side of the major
      papilla in patients with colorectal adenoma/carcinoma than in those without
      colorectal adenoma/carcinoma (27 of 51 [52.9%] vs. 5 of 27 [18.5%], p = 0.003,
      chi-square test). CONCLUSION: SNADA patients showed comorbidity with not only
      colorectal adenoma/carcinoma but also gastric cancer. H. pylori infection is
      known to cause gastric cancer and may influence tumorigenesis of SNADA lesions at
      the oral side of the major papilla.

PMID- 25582658
TI  - Mechanical complications with one hundred and thirty eight (antibiotic-laden)
      cement spacers in the treatment of periprosthetic infection after total hip
      arthroplasty.
AB  - PURPOSE: Periprosthetic infection after total hip arthroplasty is a devastating
      complication. A two-stage protocol with the temporary insertion of an antibiotic
      laden cement spacer is the gold standard treatment for chronic infections
      (Clinics (Sao Paulo) 62:99-108, 2007; Clin Orthop Relat Res 427:37-46, 2004; J
      Arthroplast 14:175-181, 1999; Clin Orthop Relat Res 467:1848-1858, 2009; J
      Arthroplast 20:874-879, 2005; J Arthroplast 24: 607-613, 2009; Clin Orthop Relat
      Res 469:1009-1015, 2011; Hip Int 20:26-33, 2010; J Arthroplast 24:1051-1060,
      2009; J Bone Joint Surg Br 91:44-51, 2009). Some authors, however (Int J Med Sci
      6(5):265-73, 2009), report mechanical complication rates with spacers in excess
      of 50%.Therefore, the aim of this study is to determine (1) the mechanical
      complications associated with enclosed articulating partial load-bearing spacers
      when treating periprosthetic hip infections and (2) possible factors of
      influence. METHODS: Between 2000 and 2011, 138 patients received an antibiotic
      laden cement spacer as part of a two-stage protocol. The overall frequency of
      complications (spacer fracture, dislocation, femoral fracture with enclosed
      spacer, spacer fracture with dislocation, protusion into the pelvis) was
      recorded. Potential influencing factors ('mould spacer' vs. handmade spacer,
      Steinmann pins as an endoskeleton, addition of vancomycin into the spacer) were
      analysed. RESULTS: The mean age at the time of the first stage operation was 69.3
      +/- 10.5 years. Overall, 27 of 138 patients suffered one of the above-mentioned
      complications (19.6%). Spacer fracture occurred in 12 cases (8.7%) and
      dislocation in another 12 (8.7%). There was also one periprosthetic femoral
      fracture with a spacer in situ, one dislocation with a simultaneous spacer
      fracture, and one protrusion into the pelvis (0.7% each). CONCLUSIONS: Our data
      revealed an overall complication rate of 13.2% with a mould spacer enclosing a
      Steinman pin. The mechanical complication rate of over 50% reported by some
      authors cannot be confirmed. As a consequence, we recommend using a mould spacer
      with an enclosed Steinman pin as an endoskeleton to minimize the complication
      rate.

PMID- 25582659
TI  - PEITC induces apoptosis of Human Brain Glioblastoma GBM8401 Cells through the
      extrinsic- and intrinsic -signaling pathways.
AB  - Glioblastoma is the most common and most aggressive primary brain malignancy. The
      multimodality treatments for this tumor including surgery, radiotherapy, and
      chemotherapy, are still not completely satisfied. Phenethyl isothiocyanate
      (PEITC), one member of the isothiocyanate family, has been shown to induce
      apoptosis in many human cancer cells. In this study, we investigate the pro
      apoptotic effects caused by PETIC in human brain glioblastoma multiforme GBM 8401
      cells. In our data, PEITC induced the cell morphological changes and decreased
      the cell viability of GBM8401 cells in a dose- and time-dependent manner.
      Moreover, the analysis of cell cycle distribution detected by flow cytometry
      showed that PEITC induced significantly sub-G1 phase (apoptotic population) in
      GBM 8401 cells. In addition, PEITC promoted the production of reactive oxygen
      species (ROS) and increase in [Ca2+]I, but decreased the mitochondrial membrane
      potential (DeltaPsim) in treated cells. PEITC also induced caspases activities in
      GBM 8401 cells. Results from Western blot analysis indicated that PEITC promoted
      Fas, FasL, FADD, TRAIL, caspase-8, -9, -3, increased the pro-apoptotic protein
      (Bax, Bid and Bak), and inhibited the anti-apoptotic proteins (Bcl-2 and Bcl-xl)
      in GBM 8401 cells. Furthermore, PEITC promoted the release of cytochrome c, AIF
      and Endo G. GADD153, GRP 78, XBP-1 and IRE-1alpha, Calpain I and II in GBM 8401
      cells. PEITC also promoted the expression of associated protein with endoplasmic
      reticulum (ER) stress. PEITC induces apoptosis through the extrinsic (death
      receptor) pathway, dysfunction of mitochondria, ROS induced ER stress, intrinsic
      (mitochondrial) pathway in GBM 8401 cells. The possible molecular mechanisms and
      signaling pathways of the anti-cancer properties of PEITC for human brain
      glioblastoma cells were postulated. 

PMID- 25582660
TI  - Fast cooling in dispersively and dissipatively coupled optomechanics.
AB  - The cooling performance of an optomechanical system comprising both dispersive
      and dissipative coupling is studied. Here, we present a scheme to cool a
      mechanical resonator to its ground state in finite time using a chirped pulse. We
      show that there is distinct advantage in using the chirp-pulse scheme to cool a
      resonator rapidly. The cooling behaviors of dispersively and dissipatively
      coupled system is also explored with different types of incident pulses and
      different coupling strengths. Our scheme is feasible in cooling the resonator for
      a wide range of the parameter region. 

PMID- 25582661
TI  - Intimate partner relationship distress in the DSM-5.
AB  - Over the past 40 years, a large body of literature has documented intimate
      partner relationship distress as a primary reason for seeking mental health
      services as well as an integral factor in the prognosis and treatment of a range
      of mental and physical health conditions. In recognition of its relevance to
      clinical care, the description of intimate partner relationship distress has been
      expanded in the DSM-5. Nonetheless, this is irrelevant if the DSM-5 code for
      intimate partner relationship distress is not reliably used in clinical practice
      and research settings. Thus, with the goal of dissemination in mind, the purpose
      of this paper was to provide clinicians and researchers with specific guidelines
      on how to reliably assess intimate partner relationship distress and how this
      information can be used to inform treatment planning. In addition to the
      implications for direct clinical care, we discuss the importance of reliable
      assessment and documentation of intimate partner relationship distress for future
      progress in epidemiology, etiology, and public health research. 

PMID- 25582662
TI  - Absolute copy number from the statistics of the quantification cycle in replicate
      quantitative polymerase chain reaction experiments.
AB  - The quantification cycle (Cq) is widely used for calibration in real-time
      quantitative polymerase chain reaction (qPCR), to estimate the initial amount, or
      copy number (N0), of the target DNA. Cq may be defined several ways, including
      the cycle where the detected fluorescence achieves a prescribed threshold level.
      For all methods of defining Cq, the standard deviation from replicate experiments
      is typically much greater than the estimated standard errors from the least
      squares fits used to obtain Cq. For moderate-to-large copy number (N0 > 10(2)),
      pipet volume uncertainty and variability in the amplification efficiency (E)
      likely account for most of the excess variance in Cq. For small N0, the
      dispersion of Cq is determined by the Poisson statistics of N0, which means that
      N0 can be estimated directly from the variance of Cq. The estimation precision is
      determined by the statistical properties of chi(2), giving a relative standard
      deviation of ~(2/n)(1/2), where n is the number of replicates, for example, a 20%
      standard deviation in N0 from 50 replicates. 

PMID- 25582663
TI  - Insight into the interactive residues between two domains of human somatic
      Angiotensin-converting enzyme and Angiotensin II by MM-PBSA calculation and
      steered molecular dynamics simulation.
AB  - Angiotensin-converting enzyme (ACE), a membrane-bound zinc metallopeptidase,
      catalyzes the formation of Angiotensin-II (AngII) and the deactivation of
      bradykinin in the renin-angiotensin-aldosterone and kallikrein-kinin systems. As
      a hydrolysis product of ACE, AngII is regarded as an inhibitor and displays
      stronger competitive inhibition in the C-domain than the N-domain of ACE.
      However, the AngII binding differences between the two domains and the mechanisms
      behind AngII dissociation from the C-domain are rarely explored. In this work,
      molecular docking, Molecular Mechanics/Poisson-Boltzmann Surface Area
      calculation, and steered molecular dynamics (SMD) are applied to explore the
      structures and interactions in the binding or unbinding of AngII with the two
      domains of human somatic ACE. Calculated free energy values suggest that the C
      domain-AngII complex is more stable than the N-domain-AngII complex, consistent
      with available experimental data. SMD simulation results imply that electrostatic
      interaction is dominant in the dissociation of AngII from the C-domain. Moreover,
      Gln106, Asp121, Glu123, and Tyr213 may be the key residues in the unbinding
      pathway of AngII. The simulation results in our work provide insights into the
      interactions between the two domains of ACE and its natural peptide inhibitor
      AngII at a molecular level. Moreover, the results provide theoretical clues for
      the design of new inhibitors. 

PMID- 25582666
TI  - Correction.
AB  - [This corrects the article DOI: 10.1136/bmjresp-2013-000007.]. 

PMID- 25582664
TI  - Current status and prospects for the study of Nicotiana genomics, genetics, and
      nicotine biosynthesis genes.
AB  - Nicotiana, a member of the Solanaceae family, is one of the most important
      research model plants, and of high agricultural and economic value worldwide. To
      better understand the substantial and rapid research progress with Nicotiana in
      recent years, its genomics, genetics, and nicotine gene studies are summarized,
      with useful web links. Several important genetic maps, including a high-density
      map of N. tabacum consisting of ~2,000 markers published in 2012, provide tools
      for genetics research. Four whole genome sequences are from allotetraploid
      species, including N. benthamiana in 2012, and three N. tabacum cultivars (TN90,
      K326, and BX) in 2014. Three whole genome sequences are from diploids, including
      progenitors N. sylvestris and N. tomentosiformis in 2013 and N. otophora in 2014.
      These and additional studies provide numerous insights into genome evolution
      after polyploidization, including changes in gene composition and transcriptome
      expression in N. tabacum. The major genes involved in the nicotine biosynthetic
      pathway have been identified and the genetic basis of the differences in nicotine
      levels among Nicotiana species has been revealed. In addition, other progress on
      chloroplast, mitochondrial, and NCBI-registered projects on Nicotiana are
      discussed. The challenges and prospects for genomic, genetic and application
      research are addressed. Hence, this review provides important resources and
      guidance for current and future research and application in Nicotiana. 

PMID- 25582665
TI  - A novel fragment based strategy for membrane active antimicrobials against MRSA.
AB  - Membrane active antimicrobials are a promising new generation of antibiotics that
      hold the potential to avert antibiotic resistance. However, poor understanding of
      the action mechanism and the lack of general design principles have impeded their
      development. Here we extend the concept of fragment based drug design and propose
      a pharmacophore model based on first principles for the design of membrane active
      antimicrobials against Gram positive pathogens. Elaborating on a natural xanthone
      based hydrophobic scaffold, two derivatives of the pharmacophore model are
      proposed, and these demonstrate excellent antimicrobial activity. Rigorous
      molecular dynamics simulations combined with biophysical experiments suggest a
      three-step mechanism of action (absorption-translocation-disruption) which allows
      us to identify key factors for the practical optimization of each fragment of the
      pharmacophore. Moreover, the model matches the structures of several membrane
      active antimicrobials which are currently in clinical trials. Our model provides
      a novel and rational approach for the design of bactericidal molecules that
      target the bacterial membrane. 

PMID- 25582667
TI  - Long-term course of oxaliplatin-induced polyneuropathy: a prospective 2-year
      follow-up study.
AB  - This prospective study sought to identify the potential reversibility of
      oxaliplatin-induced peripheral neuropathy (OXAIPN) by following-up its long-term
      course 2 years after discontinuation of oxaliplatin (OXA)-based chemotherapy.
      Participants were 91 colorectal cancer patients treated with OXA-based
      chemotherapy. Neurological assessment, clinical Total Neuropathy Score(c)
      (TNSc(c)) and nerve conduction studies were performed at baseline (T0), the end
      of chemotherapy (T1) and 2 years (T2) after discontinuation of chemotherapy. A
      total of 73 of 91 (80%) patients experienced OXAIPN at T1. At a median follow-up
      of 25 months, persistence of chronic OXAIPN was present in 61 of 73 patients
      (84%) and complete resolution was present in 12 patients (17%). Longitudinal
      comparison of TNSc(c) values between T1 and T2 revealed that the overall severity
      of OXAIPN in those 61 patients significantly decreased over time. Median TNSc(c)
      values were nine (range: 2-15) at T1 vs. four (range: 2-12) at T2 (P < 0.001).
      Likewise, sensory nerve conduction measures at T2 significantly improved in all
      sensory nerves tested, compared with T1. Severity of OXAIPN at T2 was
      significantly associated (P < 0.001) with high severity of OXAIPN at T1. In
      conclusion, persistence of OXAIPN beyond 2 years after finishing chemotherapy is
      common. Clinical and neurophysiological improvement is observed, although
      recovery is often incomplete.

PMID- 25582668
TI  - Pediatric drug formulation of sodium benzoate extended-release granules.
AB  - Urea cycle disorders are a group of inherited orphan diseases leading to
      hyperammonemia. Current therapeutic strategy includes high doses of sodium
      benzoate leading to three or four oral intakes per day. As this drug is currently
      available in capsules or in solution, children are either unable to swallow the
      capsule or reluctant to take the drug due to its strong bitter taste. The
      objective of the present study was to develop solid, multiparticulate
      formulations of sodium benzoate, which are suitable for pediatric patients (i.e.
      flavor-masked, easy to swallow and with a dosing system). Drug layering and
      coating in a fluidized bed were applied for preparing sustained-release granules.
      Two types of inert cores (GalenIQ(r) and Suglets(r)) and three different polymers
      (Kollicoat(r), Aquacoat(r) and Eudragit(r)) were tested in order to select the
      most appropriate polymer and starter core for our purpose. Physical
      characteristics and drug release profiles of the pellets were evaluated. A
      Suglets(r) core associated with a Kollicoat(r) coating seems to be the best
      combination for an extended release of sodium benzoate. A curing period of 8 h
      was necessary to complete film formation and the resulting drug release pattern
      was found to be dependent of the acidity of the release medium.

PMID- 25582670
TI  - Bilateral association of pecs I block and serratus plane block for postoperative
      analgesia after double modified radical mastectomy.

PMID- 25582671
TI  - Recent negative clinical trials in septic patients: maybe a good thing?

PMID- 25582669
TI  - Epidemiology and clinical outcome of Healthcare-Associated Infections: a 4-year
      experience of an Italian ICU.
AB  - BACKGROUND: Due to their impact on the outcome, hospital-acquired infections
      (HAIs) in ICUs represent a critical issue of patients' assistance. This study
      describes microbiological and clinical findings of a surveillance program
      covering 4 years in an Italian ICU. METHODS: Patients staying for >48 hours were
      prospectively followed until discharge or death. For each patient, infections
      after admissions, duration of device exposure and causal pathogens were noted. A
      multivariable logistic regression analysis concerning ICU mortality was made.
      RESULTS: Incidence density rates were 23.14 VAPs, 6.6 CLABSIs and 5.45 CAUTIs
      (per 1000 device-days) with an increase in yearly rates during the study period
      (P<0.001). Use of invasive devices was significantly longer among infected
      patients (P<0.001, for each), whose proportion was higher among medical
      admissions (P=0.009). The most frequent source of infection was the lung (78%),
      followed by bloodstream (23%). MSSA was the most frequently isolated pathogen
      (26%) but Gram-negatives were found in 86.1% of infected patients, with a high
      degree of resistance to carbapenems (27.5% for Klebsiella pneumoniae). APACHE
      score, immunosuppression, duration of mechanical ventilation, surgical admission
      and abdominal infections were independent predictors of ICU mortality (P<0.001;
      P<0.001; P=0.006; P=0.027; P=0.006, respectively). CONCLUSION: Our infection
      rates are higher than those reported by other studies. The use of devices and a
      medical admission share a significant relationship with infection presence. A
      greater degree of organ failure and the development of an abdominal sepsis are
      risk factors for mortality.

PMID- 25582672
TI  - Occurrence of emerging and priority pollutants in municipal reverse osmosis
      concentrates.
AB  - This paper aimed to investigate the occurrence and concentrations of emerging and
      priority pollutants in the municipal reverse osmosis concentrate (ROC) using
      liquid-liquid extraction (LLE) followed by gas chromatography-mass spectrometry.
      The results indicated that there were varieties of pollutants, including
      chlorinated organic compounds, polycyclic aromatic hydrocarbons (PAHs), phthalate
      esters (PAEs), pharmaceutical and personal care products (PPCPs), herbicides and
      flame retardants, in the ROC. Most of the pollutants were quantified, and the
      performance of the analytical method was explored. For most of the target
      compounds, the mean recoveries at two concentration levels (0.17 MUg L(-1) and
      1.67 MUg L(-1)) ranged from 70% to 130% and the relative standard deviation (RSD)
      values were less than 20%, indicating excellent accuracy and precision. Typical
      concentrations of most of the pollutants were as low as tens or hundreds of ng L(
      1), whereas others were as high as several MUg L(-1) (such as, the concentration
      of 2-chloroethyl ether was 1.42 MUg L(-1), of caffeine was 3.73 MUg L(-1), and of
      benzyl butyl phthalate was 4.90 MUg L(-1)). 

PMID- 25582673
TI  - Integration of chemotaxis, transport and catabolism in Pseudomonas putida and
      identification of the aromatic acid chemoreceptor PcaY.
AB  - Aromatic and hydroaromatic compounds that are metabolized through the beta
      ketoadipate catabolic pathway serve as chemoattractants for Pseudomonas putida
      F1. A screen of P. putida F1 mutants, each lacking one of the genes encoding the
      18 putative methyl-accepting chemotaxis proteins (MCPs), revealed that pcaY
      encodes the MCP required for metabolism-independent chemotaxis to vanillate,
      vanillin, 4-hydroxybenzoate, benzoate, protocatechuate, quinate, shikimate, as
      well as 10 substituted benzoates that do not serve as growth substrates for P.
      putida F1. Chemotaxis was induced during growth on aromatic compounds, and an
      analysis of a pcaY-lacZ fusion revealed that pcaY is expressed in the presence of
      beta-ketoadipate, a common intermediate in the pathway. pcaY expression also
      required the transcriptional activator PcaR, indicating that pcaY is a member of
      the pca regulon, which includes three unlinked gene clusters that encode five
      enzymes required for the conversion of 4-hydroxybenzoate to tricarboxylic acid
      cycle intermediates as well as the major facilitator superfamily transport
      protein PcaK. The 4-hydroxybenzoate permease PcaK was shown to modulate the
      chemotactic response by facilitating the uptake of 4-hydroxybenzoate, which leads
      to the accumulation of beta-ketoadipate, thereby increasing pcaY expression. The
      results show that chemotaxis, transport and metabolism of aromatic compounds are
      intimately linked in P. putida. 

PMID- 25582674
TI  - Serratia marcescens outbreak in a neonatal intensive care unit: crucial role of
      implementing hand hygiene among external consultants.
AB  - BACKGROUND: Serratia marcescens represents an important pathogen involved in
      hospital acquired infections. Outbreaks are frequently reported and are difficult
      to eradicate. The aim of this study is to describe an outbreak of Serratia
      marcescens occurred from May to November 2012 in a neonatal intensive care unit,
      to discuss the control measures adopted, addressing the role of molecular biology
      in routine investigations during the outbreak. METHODS: After an outbreak of
      Serratia marcescens involving 14 neonates, all admitted patients were screened
      for rectal and ocular carriage every two weeks. Extensive environmental sampling
      procedure and hand sampling of the staff were performed. Antimicrobial
      susceptibility pattern and molecular analysis of isolates were carried out.
      Effective hand hygiene measures involving all the external consultants has been
      implemented. Colonized and infected babies were cohorted. Dedicated staff was
      established to care for the colonized or infected babies. RESULTS: During the
      surveillance, 65 newborns were sampled obtaining 297 ocular and rectal swabs in
      five times. Thirty-four Serratia marcescens isolates were collected: 11 out of 34
      strains were isolated from eyes, being the remaining 23 isolated from rectal
      swabs. Two patients presented symptomatic conjunctivitis. Environmental and hand
      sampling resulted negative. During the fifth sampling procedure no colonized or
      infected patients have been identified. Two different clones have been
      identified. CONCLUSIONS: Ocular and rectal colonization played an important role
      in spread of infections. Implementation of infection control measures, involving
      also external specialists, allowed to control a serious Serratia marcescens
      outbreak in a neonatal intensive care unit.

PMID- 25582675
TI  - Evolution of the major discoveries in electrocardiology.

PMID- 25582676
TI  - Electrocardiogram in patients with Takotsubo syndrome versus anterior ST
      elevation myocardial infarction.

PMID- 25582677
TI  - Stability of depressive symptoms over 3 months post-partum.
AB  - AIM: Prolonged depression during the post-partum period is associated with
      maternal and infant mortality and morbidity. Less attention has been given to
      factors that predict the persistence of depression beyond the first 3 months post
      partum. METHODS: From a longitudinal cohort of 2279 women who attended
      Mazandaran's primary health centres in 2009, 478 women with an Edinburgh
      Postnatal Depression Scale (EPDS) score of 12 or greater in the third trimester
      of pregnancy were recruited. Persistently depressed women (depressed at all three
      occasions: during pregnancy, and at 2 and 12 weeks post-partum) were compared
      with those without depression to determine demographic, cultural, obstetric and
      biopsychosocial predictors for persistence of depression. Data were analysed
      using chi-square test, t-test and logistic regression models. RESULTS: The
      stability of depression was found in 193 (46.2 %) of 418 depressed cases who were
      followed up over the study period. Of those mothers who scored more than the
      threshold of 12 during the third trimester of pregnancy, 277 (66.3%) and 221
      (52.9%) had high EPDS at 2 and 12 weeks post-partum. Psychological distress
      (based upon the General Health Questionnaire), low maternal parental self
      efficacy (based upon the Parental Expectation Survey) and perceived social
      isolation (based upon the Network Orientation Scale) were independent predictors
      of persistent depression. CONCLUSION: Fewer depressed mothers in this study were
      found to recover during the first 3 months after giving birth. Psychosocial
      factors predicted sustained depression from pregnancy to 3 months post-partum.
      The findings highlight the significance of support in enhancing maternal mental
      health.

PMID- 25582678
TI  - Nanospot soldering polystyrene nanoparticles with an optical fiber probe laser
      irradiating a metallic AFM probe based on the near-field enhancement effect.
AB  - With the development of nanoscience and nanotechnology for the bottom-up
      nanofabrication of nanostructures formed from polystyrene nanoparticles, joining
      technology is an essential step in the manufacturing and assembly of nanodevices
      and nanostructures in order to provide mechanical integration and connection. To
      study the nanospot welding of polystyrene nanoparticles, we propose a new
      nanospot-soldering method using the near-field enhancement effect of a metallic
      atomic force microscope (AFM) probe tip that is irradiated by an optical fiber
      probe laser. On the basis of our theoretical analysis of the near-field
      enhancement effect, we set up an experimental system for nanospot soldering; this
      approach is carried out by using an optical fiber probe laser to irradiate the
      AFM probe tip to sinter the nanoparticles, providing a promising technical
      approach for the application of nanosoldering in nanoscience and nanotechnology. 

PMID- 25582680
TI  - Excitation of Sodium Atoms Attached to Helium Nanodroplets: The 3p <- 3s
      Transition Revisited.
AB  - The dynamics of Na atoms on the surface of helium nanodroplets following
      excitation via the 3p <- 3s transition has been investigated using state-specific
      ion-based detection of the products. Excitation of the system to the 3p (2)Pi
      states is found to lead to the desorption of both bare Na and NaHe exciplexes.
      The associated speed distributions point to an impulsive desorption process for
      Na products and a thermally driven process for the NaHe exciplexes. In contrast,
      excitation of the 3p (2)Sigma state leads exclusively to the impulsive desorption
      of Na atoms. In this case, the desorption is accompanied by a helium-induced
      relaxation process, as evidenced by the large fraction of detected Na (2)P1/2
      atoms. The relaxation process is thought to be related to a crossing between the
      (2)Pi1/2 and (2)Sigma potential energy curves at large distance. 

PMID- 25582682
TI  - Permanent seed brachytherapy for clinically localized prostate cancer: long-term
      outcomes in a 700 patient cohort.
AB  - PURPOSE: Few large European studies have evaluated long-term outcomes for
      permanent prostate brachytherapy (PPB) as monotherapy for clinically localized
      prostate cancer. The objective of the present study was to evaluate long-term
      survival in this patient profile. METHODS AND MATERIALS: Retrospective study of
      700 patients who underwent transperineal ultrasound-guided iodine-125 PPB (145
      Gy) between January 2000 and July 2012. Median age was 64.8 years (range, 35-79).
      Most patients (638 of 700; 91%) had low-risk disease (D'Amico criteria). Eighty
      five patients (12%) received hormonal treatment. Overall survival, cause-specific
      survival, and biochemical relapse-free survival were calculated and estimated
      using actuarial and Kaplan-Meier methods. Differences between groups were
      assessed using the log-rank test. RESULTS: Median followup was 63 months (range,
      6-164). At 5- and 10-year followup, respectively, overall survival was 94% (95%
      confidence interval [CI], 92-96) and 84% (95% CI, 78-90); cause-specific survival
      was 100% and 97% (95% CI, 95-99); and biochemical relapse-free survival was 95%
      (95% CI, 93-97) and 85% (95% CI, 79-91). CONCLUSIONS: The long-term results
      presented in this report confirm previous studies and provide additional support
      for the use of PPB in patients with favorable-risk prostate cancer. Seed
      brachytherapy provides excellent long-term results in this patient profile.

PMID- 25582683
TI  - Successful treatment with telaprevir-based regimens for chronic hepatitis C
      results in significant improvements to serum markers of liver fibrosis.
AB  - Patients infected with hepatitis C virus (HCV) have differing levels of liver
      health when they initiate treatment. We sought to quantify whether liver health
      improves following successful treatment with telaprevir-based antiviral regimens.
      We performed a retrospective analysis of data generated from one Phase 2 and two
      Phase 3 telaprevir clinical studies. 1208 patients treated with a telaprevir
      based regimen were included in the analysis. Patients were grouped according to
      their baseline Metavir score (F0-F1, F2 and F3-F4) and whether or not they
      attained sustained virologic response (SVR). Scores from four biomarker tests,
      FibroTest, APRI, FIB-4 and Forns' Score, were monitored both before and after HCV
      treatment. All four of these tests differentiated the fibrosis stage as
      determined by Metavir score at baseline. Consistent with previous studies,
      patients who attained SVR exhibited significant improvements in scores from each
      of these tests after treatment. These improvements remained significant even when
      patients were grouped according to their baseline Metavir score. On average, the
      scores from different tests exhibited differential improvements following SVR.
      Improvements in APRI scores corresponded to complete fibrosis regression (i.e. a
      Metavir stage of F0-F1). In contrast, improvements in scores from Forns' Score,
      FIB-4 and FibroTest were more modest (i.e. fibrosis regression of less than a
      Metavir stage). Overall, these results demonstrated that attaining SVR with a
      telaprevir-based regimen led to significant improvements in liver health as
      determined by four biomarker tests. However, not all correlations observed
      between noninvasive markers and fibrosis stage at baseline hold after SVR is
      attained. 

PMID- 25582679
TI  - A case report comparing clinical, imaging and neuropsychological assessment
      findings in twins discordant for the VCP p.R155C mutation.
AB  - Inclusion body myopathy, Paget disease of bone and/or frontotemporal dementia is
      an autosomal dominant disease caused by mutations in the Valosin Containing
      Protein (VCP) gene. We compared clinical findings including MRI images and
      neuropsychological assessment data in affected and unaffected twin brothers aged
      56 years from a family with the p.R155C VCP gene mutation. The affected twin
      presented with a 10 year history of progressive proximal muscle weakness,
      difficulty swallowing, gastroesophageal reflux, fecal incontinence, and
      peripheral neuropathy. Comprehensive neuropsychological testing revealed rapid
      cognitive decline in the absence of any behavioral changes in a span of 1 year.
      This case illustrates that frontotemporal dementia related cognitive impairment
      may precede behavioral changes in VCP disease as compared with predominance of
      behavioral impairment reported in previous studies. Our findings suggest that
      there is a need to establish VCP disease specific tools and normative rates of
      decline to detect pre-clinical cognitive impairment among affected individuals.

PMID- 25582681
TI  - Differences in Composition of Symptom Clusters Between Older and Younger Oncology
      Patients.
AB  - CONTEXT: Older oncology patients have unique needs associated with the many
      physical, psychological, and social changes associated with the aging process.
      The mechanisms underpinning and the impact of these changes are not well
      understood. Identification of clusters of symptoms is one approach that has been
      used to elicit hypotheses about the biological and/or psychological basis for
      variations in symptom experiences. OBJECTIVES: The purposes of this study were to
      identify and compare symptom clusters in younger (<60 years) and older (>=60
      years) patients undergoing cancer treatment. METHODS: Symptom data from one
      Australian study and two U.S. studies were combined to conduct this analysis. A
      total of 593 patients receiving active treatment were dichotomized into younger
      (<60 years) and older (>=60 years) groups. Separate exploratory factor analyses
      (EFAs) were undertaken within each group to identify symptom clusters from
      occurrence ratings of the 32 symptoms assessed by the Memorial Symptom Assessment
      Scale. RESULTS: In both groups, a seven-factor solution was selected. Four
      partially concordant symptom clusters emerged in both groups (i.e.,
      mood/cognitive, malaise, body image, and genitourinary). In the older patients,
      the three unique clusters reflected physiological changes associated with aging,
      whereas in the younger group the three unique clusters reflected treatment
      related effects. CONCLUSION: The symptom clusters identified in older patients
      typically included a larger and more diverse range of physical and psychological
      symptoms. Differences also may be reflective of variations in treatment
      approaches between age groups. Findings highlight the need for better
      understanding of variation in treatment and symptom burden between younger and
      older adults with cancer.

PMID- 25582684
TI  - Do learning rates adapt to the distribution of rewards?
AB  - Studies of reinforcement learning have shown that humans learn differently in
      response to positive and negative reward prediction errors, a phenomenon that can
      be captured computationally by positing asymmetric learning rates. This
      asymmetry, motivated by neurobiological and cognitive considerations, has been
      invoked to explain learning differences across the lifespan as well as a range of
      psychiatric disorders. Recent theoretical work, motivated by normative
      considerations, has hypothesized that the learning rate asymmetry should be
      modulated by the distribution of rewards across the available options. In
      particular, the learning rate for negative prediction errors should be higher
      than the learning rate for positive prediction errors when the average reward
      rate is high, and this relationship should reverse when the reward rate is low.
      We tested this hypothesis in a series of experiments. Contrary to the theoretical
      predictions, we found that the asymmetry was largely insensitive to the average
      reward rate; instead, the dominant pattern was a higher learning rate for
      negative than for positive prediction errors, possibly reflecting risk aversion.

PMID- 25582685
TI  - In-group modulation of perceptual matching.
AB  - We report a novel effect of in-group bias on a task requiring simple perceptual
      matching of stimuli. Football fans were instructed to associate the badges of
      their favorite football team (in-group), a rival team (out-group), and neutral
      teams with simple geometric shapes. Responses to matching in-group stimuli were
      more efficient, and discriminability was enhanced, as compared to out-group
      stimuli (rival and neutral)-a result that occurred even when participants
      responded only to the (equally familiar) geometric shapes. Across individuals,
      the in-group bias on shape matching was correlated with measures of group
      satisfaction, and similar results were found when football fans performed the
      task, in the context of both the football ground and a laboratory setting. We
      also observed effects of in-group bias on the response criteria in some but not
      all of the experiments. In control studies, the advantage for in-group stimuli
      was not found in an independent sample of participants who were not football
      fans. This indicates that there was not an intrinsic advantage for the stimuli
      that were "in-group" for football fans. Also, performance did not differ for
      familiar versus unfamiliar stimuli without in-group associations. These findings
      indicate that group identification can affect simple shape matching. 

PMID- 25582688
TI  - Strength or endurance: a question of muscle.

PMID- 25582686
TI  - CD226 as a genetic adjuvant to enhance immune efficacy induced by Ag85A DNA
      vaccination.
AB  - Antigen-85A (Ag85A) is one of the major proteins secreted by Mycobacterium
      tuberculosis. Many studies on animal models have shown that vaccination with the
      recombinant Ag85A-DNA or Ag85A protein induces powerful immune response. However,
      these vaccines cannot generate sufficient protective immunity in the systemic
      compartment. CD226, a member of the immunoglobulin superfamily, is expressed in
      the majority of NK cells, T cells, monocytes, and platelets, and can be served as
      a co-stimulator that contributes to multiple innate and adaptive responses.
      However, there has been no study where either CD226 protein or DNA has been used
      as an adjuvant for vaccine development. The aim of this study was to develop a
      novel Ag85A DNA vaccine with CD226 as the genetic adjuvant to increase the immune
      efficacy induced by Ag85A. Oral vaccination with pcDNA3.1-Ag85A-CD226 DNA induced
      potent immune responses in mice. CD226 was an effective genetic adjuvant that
      improved the immune efficacy induced by Ag85A and enhanced the activity of
      cytotoxic T lymphocytes (CTL) and NK cells in mice. Th1 dominant cytokines (i.e.
      IL-2, IFN-gamma and TNF-alpha), cellular immunity (i.e. CD4(+)IFN-gamma(+)T cells
      and CD8(+)IFN-gamma(+)T cells in splenocytes) and MLNs were also significantly
      elevated by pcDNA3.1-Ag85A-CD226 DNA vaccination. Our results suggest that CD226
      is an effective adjuvant to enhance the immune efficacy induced by Ag85A. Our
      findings provide a new strategy for the development of a DNA vaccine co
      expressing Ag85A and CD226. 

PMID- 25582687
TI  - Influence of dietary supplementation with flaxseed and lactobacilli on the cells
      of local innate immunity response in the jejunal mucosa in piglets after weaning.
AB  - A histological study was designed to determine the influence of flaxseed and/or
      lactobacilli inclusion in the diet of piglets from 10 days before to 21 days
      after weaning. The selected inflammatory cell population incidence in the piglet
      jejunal mucosa was investigated. Significantly higher numbers of myeloperoxidase
      positive (P<0.01) and CD163-positive (P<0.001) cells in the jejunal mucosa were
      recorded on the weaning day and for 7 days after (P<0.001 and P<0.01,
      respectively) in the flaxseed group compared with the basal diet. The number of
      intraepithelial lymphocytes was also significantly increased until 3 days after
      weaning (P<0.001). A prolonged significant increase in the myeloperoxidase
      positive cells and intraepithelial lymphocyte numbers in the
      flaxseed+lactobacilli group was detected. In contrast, the number of CD163
      positive cells in the flaxseed+lactobacilli group was significantly lower on the
      day of weaning (P<0.05) and 3 days after (P<0.01). The same effect was observed
      in the group with lactobacilli alone during the first 3 days after weaning
      (P<0.05 and P<0.01, respectively) and these findings indicate down-regulation of
      CD163 expression in the jejunal mucosa by lactobacilli. The presence of
      lactobacilli in the diet had a stimulatory effect on goblet cell quantity in the
      epithelium (P<0.001) and a distinct 50% reduction in the flaxseed group (P<0.01)
      compared with the basal diet was observed on the weaning day. A significant
      increase in myeloperoxidase-positive cell number in the jejunal mucosa in the
      flaxseed+lactobacilli group was the only significant difference (P<0.05 and
      P<0.01, respectively) found 21 days after weaning in comparison with all the
      other groups, indicating the pro-inflammatory effect of this feed additive
      combination. We conclude that dietary supplementation with flaxseed and
      lactobacilli on the cells of local innate immunity response in the jejunal mucosa
      in piglets after weaning might be linked with significant anti-inflammatory
      effects in the jejunal mucosa. 

PMID- 25582689
TI  - Perspectives on Ebola.

PMID- 25582690
TI  - Malaria risk factors in Dielmo, a Senegalese malaria-endemic village, between
      October and November of 2013: a case-control study.
AB  - The incidence of malaria has decreased recently in parts of Africa, coinciding
      with the widespread use of long-lasting insecticide-treated nets (LLINs) and
      artemisinin-based combination therapy (ACT). This reduction was also observed in
      Dielmo, our study area, and it was associated with the use of ACT as the first
      line treatment against malaria beginning in 2006 and the implementation of LLINs
      in 2008. However, an unexplained slight increase in malaria incidence was
      observed in October and November of 2013. The aim of this study was to identify
      individual and environmental risk factors for malaria using a case-control study
      approach. Thirty cases and sixty controls were investigated. The use of LLINs was
      protective against malaria (adjusted odds ratio [AOR] = 0.10; 95% confidence
      interval [95% CI] = 0.02-0.45; P = 0.003). The risk of malaria transmission was
      high among villagers who watched television outside the house or the bedroom
      during the night (AOR = 8.83; 95% CI = 1.39-56.22; P = 0.021). The use of LLINs
      should be reinforced by the use of individual protection measures to avoid
      malaria transmission outside of the home. 

PMID- 25582691
TI  - Real-time assessments of the strength of program implementation for community
      case management of childhood illness: validation of a mobile phone-based method
      in Malawi.
AB  - Health surveillance assistants (HSAs) in Malawi have provided community case
      management (CCM) since 2008; however, program monitoring remains challenging.
      Mobile technology holds the potential to improve data, but rigorous assessments
      are few. This study tested the validity of collecting CCM implementation strength
      indicators through mobile phone interviews with HSAs. This validation study
      compared mobile phone interviews with information obtained through inspection
      visits. Sensitivity and specificity were measured to determine validity. Using
      mobile phones to interview HSAs on CCM implementation strength indicators
      produces accurate information. For deployment, training, and medicine stocks, the
      specificity and sensitivity of the results were excellent (> 90%). The
      sensitivity and specificity of this method for drug stock-outs, supervision, and
      mentoring were lower but with a few exceptions, still above 80%. This study
      provided a rigorous assessment of the accuracy of implementation strength data
      collected through mobile technologies and is an important step forward for
      evaluation of public health programs. 

PMID- 25582692
TI  - Hepatitis B surface antigen seroprevalence among children in Papua New Guinea,
      2012-2013.
AB  - Approximately 8% of the population in Papua New Guinea (PNG) has chronic
      hepatitis B virus (HBV) infection. To decrease the burden of chronic HBV
      infection, a national 3-dose infant hepatitis B vaccination program was
      implemented starting in 1989, with a birth dose (BD) added to the schedule in
      1992. To assess the impact of the hepatitis B vaccination program, we conducted a
      serosurvey among children born after vaccine introduction. During 2012-2013, a
      cross-sectional stratified four-stage cluster survey was conducted to estimate
      hepatitis B surface antigen (HBsAg) prevalence among children 4-6 years of age.
      We collected demographic data, vaccination history, and tested children for
      HBsAg. Of 2,133 participants, 2,130 children had vaccination data by either card
      or recall: 28% received a BD; 81% received >= 3 vaccine doses. Of 2,109 children
      providing a blood sample, 60 (2.3%) tested positive for HBsAg. This is the
      largest, most geographically diverse survey of hepatitis B vaccination and HBsAg
      seroprevalence done in PNG. Progress has been made in PNG toward the Western
      Pacific Regional goal to reduce the prevalence of chronic HBV infection to < 1%
      by 2017 among 5-year-old children. Vaccination efforts should be strengthened,
      including increasing BD coverage and completing the 3-dose series. 

PMID- 25582693
TI  - Evidence of recent dengue exposure among malaria parasite-positive children in
      three urban centers in Ghana.
AB  - Blood samples of 218 children ages 2-14 years old with confirmed malaria in
      hospitals across Ghana were tested for dengue virus exposure. We detected dengue
      specific immunoglobulin M (IgM) antibodies in 3.2% of the children, indicating
      possible coinfection, and IgG antibodies in 21.6% of them, which suggests
      previous exposure. Correlates of exposure are discussed. 

PMID- 25582695
TI  - Increasing prevalence of Plasmodium vivax among febrile patients in Nouakchott,
      Mauritania.
AB  - The occurrence of Plasmodium vivax malaria was reported in Nouakchott, Mauritania
      in the 1990s. Several studies have suggested the frequent occurrence of P. vivax
      malaria among Nouakchott residents, including those without recent travel history
      to the southern part of the country where malaria is known to be endemic. To
      further consolidate the evidence for P. vivax endemicity and the extent of
      malaria burden in one district in the city of Nouakchott, febrile illnesses were
      monitored in 2012-2013 in the Teyarett health center. The number of laboratory
      confirmed P. vivax cases has attained more than 2,000 cases in 2013. Malaria
      transmission occurs locally, and P. vivax is diagnosed throughout the year.
      Plasmodium vivax malaria is endemic in Nouakchott and largely predominates over
      Plasmodium falciparum. 

PMID- 25582694
TI  - AKT network of genes and impaired myocardial contractility during murine acute
      Chagasic myocarditis.
AB  - Chagasic disease is associated with high morbidity in Latin America. Acute
      Chagasic myocarditis is consistently found in acute infections, but little is
      known about its contribution to chronic cardiomyopathy. The aim of the study was
      to phenotypically characterize two strains of mice with differential Chagas
      infection susceptibility and correlate strain myocarditis phenotypes with heart
      tissue gene expression. C57BL/6J and Balb/c mice were injected intraperitoneally
      with 0 or 150-200 tissue-derived trypomastigotes (Tulahuen strain).
      Echocardiograms, brain natriuretic peptide, and troponin were measured. Heart
      tissue was harvested for histopathological analysis and gene expression profiling
      on microarrays. Genes differently expressed between infected Balb/c and C57BL/6J
      mice were identified. Echocardiograms showed differences in Balb/c versus
      C57BL/6J infected mice in heart rate (413 versus 476 beats per minute; P =
      0.0001), stroke volume (31.9 +/- 9.3 versus 39.2 +/- 5.5 MUL; P = 0.03), and
      cardiac output (13.1 +/- 3.5 versus 18.7 +/- 3.2 MUL/min; P = 0.002). Gene
      expression at 4 weeks analysis showed 32 statistically significant (q value <
      0.05) differentially expressed genes between infected Balb/c and C57BL/6J mice
      that were enriched for genes related to the protein kinase B (AKT) pathway. These
      specific phenotypic features of cardiac response during acute Chagasic
      myocarditis may, in part, be related to host AKT network regulation. 

PMID- 25582696
TI  - N-fluorobenzenesulfonimide based functionalization of C60.
AB  - The reaction of N-fluorobenzenesulfonimide (NFSI) with C60 and exploration of the
      product as a precursor for various 1,2- and 1,4-bisfullerene adducts are
      reported. NFSI is also found to act as an oxidant in the reaction of C60 with
      cyclic amines such as pyrrolidine yielding tetraaminoaziridino adducts. 

PMID- 25582698
TI  - A cucurbit[5]uril analogue from dimethylpropanediurea-formaldehyde condensation.
AB  - A new host was prepared for the first time from propanediurea-formaldehyde
      condensation. is soluble in both water and common organic solvents, and binds
      protonated amines in a 1 : 2 stoichiometry in H2O with the K1 and K2 values on
      the order of 10(3) M(-1). The self-assembly of with 1,4-xylylene diamine
      dihydrochloride results in the formation of a linear supramolecular polymer. 

PMID- 25582697
TI  - PRMT5 is required for lymphomagenesis triggered by multiple oncogenic drivers.
AB  - Protein arginine methyltransferase 5 (PRMT5) has been implicated as a key
      modulator of lymphomagenesis. Whether PRMT5 has overt oncogenic function in the
      context of leukemia/lymphoma and whether it represents a therapeutic target
      remains to be established. We demonstrate that inactivation of PRMT5 inhibits
      colony-forming activity by multiple oncogenic drivers, including cyclin D1, c
      MYC, NOTCH1, and MLL-AF9. Furthermore, we demonstrate that PRMT5 overexpression
      specifically cooperates with cyclin D1 to drive lymphomagenesis in a mouse model,
      revealing inherent neoplastic activity. Molecular analysis of lymphomas revealed
      that arginine methylation of p53 selectively suppresses expression of crucial
      proapoptotic and antiproliferative target genes, thereby sustaining tumor cell
      self-renewal and proliferation and bypassing the need for the acquisition of
      inactivating p53 mutations. Critically, analysis of human tumor specimens reveals
      a strong correlation between cyclin D1 overexpression and p53 methylation,
      supporting the biomedical relevance of this pathway. SIGNIFICANCE: We have
      identified and functionally validated a crucial role for PRMT5 for the inhibition
      of p53-dependent tumor suppression in response to oncogenic insults. The
      requisite role for PRMT5 in the context of multiple lymphoma/leukemia oncogenic
      drivers suggests a molecular rationale for therapeutic development.

PMID- 25582699
TI  - [Results of therapeutics strategy of protein-energy wasting in chronic
      hemodialysis: a prospective study during 12 months].
AB  - INTRODUCTION: Undernutrition (UN) in chronic hemodialysis (CHD) is a recurrent
      complication and constitutes a major public health problem. This work aims to
      evaluate the effects of our nutritional strategy (NS) developed among
      malnourished patients (pts) in CHD. This is a prospective observational study
      conducted for 12 months (M) in a cohort of 132 pts in CHD including 49 women,
      mean age 66 +/- 16 years and the dialysis vintage 72 +/- 74 months. This NS is
      based on the action of a multidisciplinary team; it provides for moderate UN pts
      one first phase of an optimization of protein and energy intake in the daily
      meals; then depending on the clinical course a second phase of oral
      supplementation at home. For severe UN pts, the optimization of daily meals and
      the oral supplements at home are reinforced with perdialytic oral
      supplementation. This modality was also prescribed for moderate UN pts with poor
      compliance at home. In case of loss of appetite, anorexia, gastrointestinal
      intolerance or inadequate oral intakes the relay is made by the intradialytic
      parenteral nutrition (IPN). Methods consist in the evaluation of the serum
      albumin (ALB), CRP, normalized PCR (nPCR), and Kt/V ratio of urea at baseline
      (day (D) 0) and at endpoint (M12). The ALB was measured by immunoturbidimetry.
      Three nutritional profiles were defined, severe UN if ALB <= 35 g/L, moderate UN
      if 35 <ALB <38 g/L, no UN if ALB >= 38 g/L. The therapeutic goal is to obtain a
      target ALB >= 38 g/L, protein intake exceeding 1g/kg/d and energy intake
      exceeding 35 Kcal/kg/d. The criteria of effectiveness are obtaining the ALB
      defined target, changes in numbers of pts in 3 nutritional profiles and mortality
      rate on 1 year. RESULTS: We observe a significant improvement in all nutritional
      indicators at M12. The numbers of pts with severe UN and moderate UN decreased (P
      < 0,05), respectively from 32 to 14% and from 27 to 18% (D0 versus M12). The UN
      frequency has been reduced about 50% (P < 0,05) lowering from 59 to 32%. The
      mortality rate of 4% (5/132 pts) in 1 year was very low. The therapeutic goal is
      achieved under the conjunction of 3 essential conditions, the improvement of the
      inflammatory syndrome, an effective dialysis and optimal protein and caloric
      intake. At the start and the end of the study, the role of inflammation appears
      crucial because ALB is greater if CRP <10mg/L versus CRP >= 10 mg/L (at M12: 40
      versus 38 g/L, P = 0.002); an inverse correlation is observed between CRP and ALB
      (R(2) = 0,080, P = 0.002). CONCLUSION: An effective NS reduces the frequency of
      UN in CHD, improves the quality of life the pts and lowers mortality rates. An
      oral nutritional supplement during dialysis constitutes an important component of
      treatment. The control of inflammation and optimizing dialysis are decisive
      factors of success.

PMID- 25582700
TI  - Prophylactic tranexamic acid in low-risk parturients.

PMID- 25582701
TI  - The vitamin D receptor localization and mRNA expression in ram testis and
      epididymis.
AB  - The objectives of present study were to investigate the presence of vitamin D
      receptor (VDR) in testis and epididymis of ram by polymerase chain reaction
      (PCR), to locate VDR in testis and epididymis by immunohistochemistry and to
      compare difference of VDR expression between testis and epididymis before and
      after sexual maturation by Real time-PCR and Western blot. The results showed
      that VDR exists in the testis and epididymis of ram while VDR protein in testis
      and epididymis was localized in Leydig cells, spermatogonial stem cells,
      spermatocytes, Sertoli cells and principal cells. For the adult ram, the amounts
      of VDR mRNA and VDR protein were less (p < 0.01) in testis than compared with
      caput, corpus and cauda epididymis. For prepubertal ram, the result showed the
      same trend (p < 0.01). However, the expression levels of VDR mRNA and VDR protein
      in caput, corpus, cauda epididymis and testis showed no significant difference (p
      > 0.05) between adult and prepubertal. In conclusion, VDR exists in testis and
      epididymis of ram, suggesting 1alpha,25-(OH)(2)VD(3) may play a role in ram
      reproduction.

PMID- 25582702
TI  - Bacterial and fungal microflora on the external genitalia of male donkeys (Equus
      asinus).
AB  - This study was undertaken to investigate the bacterial and fungal microflora on
      the external genitalia of a population of healthy male donkeys in the state of
      Michigan, USA. The aim was to identify and determine the frequency of occurrence
      of these microorganisms using seven different isolation media and standard
      microbiological procedures. The sites (urethral fossa [fossa glandis], dorsal
      diverticulum of the urethral sinus, distal urethra, and penile surface) in the
      distal reproductive tract were cultured and each isolated microorganism
      identified. Ten different genera of gram-positive bacteria, eight different
      genera of gram-negative bacteria, and two genera of fungi were isolated from the
      external genitalia of the 43 donkeys in this study. All 43 donkeys yielded gram
      positive bacteria (2-8 species) from all four sites sampled. Arcanobacterium
      spp., Corynebacterium spp., and Bacillus spp. were the most frequently isolated
      gram-positive bacteria. Gram-negative bacteria were cultured from 16 (37.2%) of
      the 43 donkeys, with Acinetobacterlwoffii (16.3%), Oligella urethralis (11.6%),
      and Taylorellaasinigenitalis (9.3%), the most frequently isolated. Fungi were
      cultured from only 5 (11.6%) of the 43 donkeys, with Rhizopus spp. isolated from
      3 (7.0%) and Cladosporium spp. from 2 (4.7%) individuals. The testes and
      epididymides collected from 40 donkeys at time of castration were culture
      negative. Few differences were found in the bacterial flora between prepubertal
      and mature intact and castrated donkeys. Of notable interest was the scarcity of
      known equine pathogens across the population tested and isolation of T.
      asinigenitalis from normal donkeys, especially prepubertal individuals and
      previously castrated males. 

PMID- 25582703
TI  - A mechanism for asymmetric cell division resulting in proliferative
      asynchronicity.
AB  - All cancers contain an admixture of rapidly and slowly proliferating cancer
      cells. This proliferative heterogeneity complicates the diagnosis and treatment
      of patients with cancer because slow proliferators are hard to eradicate, can be
      difficult to detect, and may cause disease relapse sometimes years after
      apparently curative treatment. While clonal selection theory explains the
      presence and evolution of rapid proliferators within cancer cell populations, the
      circumstances and molecular details of how slow proliferators are produced is not
      well understood. Here, a beta1-integrin/FAK/mTORC2/AKT1-associated signaling
      pathway is discovered that can be triggered for rapidly proliferating cancer
      cells to undergo asymmetric cell division and produce slowly proliferating
      AKT1(low) daughter cells. In addition, evidence indicates that the proliferative
      output of this signaling cascade involves a proteasome-dependent degradation
      process mediated by the E3 ubiquitin ligase TTC3. These findings reveal that
      proliferative heterogeneity within cancer cell populations, in part, is produced
      through a targetable signaling mechanism, with potential implications for
      understanding cancer progression, dormancy, and therapeutic resistance.
      IMPLICATIONS: These findings provide a deeper understanding of the proliferative
      heterogeneity that exists in the tumor environment and highlight the importance
      of designing future therapies against multiple proliferative contexts. VISUAL
      OVERVIEW: A proposed mechanism for producing slowly proliferating cancer cells.
      http://mcr.aacrjournals.org/content/early/2015/01/09/1541-7786.MCR-14
      0474/F1.large.jpg.

PMID- 25582704
TI  - Sympathetic activity induced by naloxone-precipitated morphine withdrawal is
      blocked in genetically engineered mice lacking functional CRF1 receptor.
AB  - There is large body evidence indicating that stress can lead to cardiovascular
      disease. However, the exact brain areas and the mechanisms involved remain to be
      revealed. Here, we performed a series of experiments to characterize the role of
      CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated
      morphine withdrawal. The experiments were performed in the hypothalamic
      paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved
      in the regulation of cardiovascular activity, and in the right ventricle by using
      genetically engineered mice lacking functional CRF1R levels (KO). Mice were
      treated with increasing doses of morphine and withdrawal was precipitated by
      naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and
      TH phosphorylated at serine 40, was evaluated by high-performance liquid
      chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine
      withdrawal induced an enhancement of NA turnover in PVN in parallel with an
      increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we
      have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and
      PKA levels in heart. The main finding of the present study was that NA turnover,
      TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA
      expression observed during morphine withdrawal were significantly inhibited in
      CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute
      to the adaptive changes induced by naloxone-precipitated withdrawal in the heart
      and in the brain areas which modulate the cardiac sympathetic function and
      suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease
      associated to opioid addiction. 

PMID- 25582705
TI  - Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating
      HMGB1/RAGE pathway.
AB  - An abnormal high mobility group box 1 (HMGB1) activation and a decrease in
      receptor for advanced glycation end-product (RAGE) play a key role in the
      pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally
      occurring compound, which is extracted from the degradation of phenolic acids.
      However, whether PA has anti-fibrotic functions is unknown. In this study, the
      effects of PA on the transforming growth factor-beta1 (TGF-beta1)-mediated
      epithelial-mesenchymal transition (EMT) in A549 cells, on the apoptosis of human
      type I alveolar epithelial cells (AT I), on the proliferation of human lung
      fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis
      in vivo were investigated. PA treatment resulted in a reduction of EMT in A549
      cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a
      reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2
      (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was
      attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary
      fibrosis in rats with a reduction of histopathological scores and collagen
      deposition, and a lower FGF-2, PDGF, alpha-smooth muscle actin (alpha-SMA) and
      HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through
      the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited
      HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary
      fibrosis in vivo. Collectively, our results demonstrate that PA prevents
      experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. 

PMID- 25582706
TI  - Individual bile acids have differential effects on bile acid signaling in mice.
AB  - Bile acids (BAs) are known to regulate BA synthesis and transport by the
      farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However,
      the relative importance of individual BAs in regulating these processes is not
      known. Therefore, mice were fed various doses of five individual BAs, including
      cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA),
      lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various
      concentrations for one week to increase the concentration of one BA in the
      enterohepatic circulation. The mRNA of BA synthesis and transporting genes in
      liver and ileum were quantified. In the liver, the mRNA of SHP, which is the
      prototypical target gene of FXR, increased in mice fed all concentrations of BAs.
      In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at
      lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1,
      the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than
      CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible
      for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA.
      Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp)
      nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but
      an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with
      FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators
      than CDCA and LCA when fed to mice, and thus they are more effective in
      decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and
      the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the
      expression of Abcg5/Abcg8, which is responsible for biliary cholesterol
      excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp
      or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at
      physiological and pharmacological concentrations of BAs. 

PMID- 25582707
TI  - Domino [4 + 1]-annulation of alpha,beta-unsaturated delta-amino esters with
      Rh(II)-carbenoids - a new approach towards multi-functionalized N-aryl
      pyrrolidines.
AB  - Catalytic decomposition of diazomalonates and other diazoesters using Rh(II)- and
      Cu(II)-complexes in the presence of alpha,beta-unsaturated delta-(N-aryl)amino
      esters gives rise to the formation of multi-functionalized pyrrolidines with
      yields of up to 82%. The reaction apparently occurs as a domino process involving
      the initial N-ylide formation followed by intramolecular Michael addition to the
      conjugated system of amino esters to afford the pyrrolidine heterocycle. The
      whole process can also be classified as a [4 + 1]-annulation of the delta-amino
      alpha,beta-unsaturated ester with the carbenoid intermediate.

PMID- 25582708
TI  - Lack of a type-2 glycosyltransferase in the fish pathogen Flavobacterium
      psychrophilum determines pleiotropic changes and loss of virulence.
AB  - Flavobacterium psychrophilum is an important fish pathogen, responsible for Cold
      Water Disease, with a significant economic impact on salmonid farms worldwide. In
      spite of this, little is known about the bacterial physiology and pathogenesis
      mechanisms, maybe because it is difficult to manipulate, being considered a
      fastidious microorganism. Mutants obtained using a Tn4351 transposon were
      screened in order to identify those with alteration in colony morphology, colony
      spreading and extracellular proteolytic activity, amongst other phenotypes. A F.
      psychrophilum mutant lacking gliding motility showed interruption of the FP1638
      locus that encodes a putative type-2 glycosyltransferase (from here on referred
      to as fpgA gene, Flavobacterium psychrophilum glycosyltransferase). Additionally,
      the mutant also showed a decrease in the extracellular proteolytic activity as a
      consequence of down regulation in the fpgA mutant background of the fpp2-fpp1
      operon promoter, responsible for the major extracellular proteolytic activity of
      the bacterium. The protein glycosylation profile of the parental strain showed
      the presence of a 22 kDa glycosylated protein which is lost in the mutant.
      Complementation with the fpgA gene led to the recovery of the wild-type
      phenotype. LD50 experiments in the rainbow trout infection model show that the
      mutant was highly attenuated. The pleiotropic phenotype of the mutant
      demonstrated the importance of this glycosyltranferase in the physiology and
      virulence of the bacterium. Moreover, the fpgA mutant strain could be considered
      a good candidate for the design of an attenuated vaccine. 

PMID- 25582711
TI  - The application of robotics to microlaryngeal laser surgery.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the performance of human subjects, using a
      prototype robotic micromanipulator controller in a simulated, microlaryngeal
      operative setting. STUDY DESIGN: Observational cross-sectional study. METHODS:
      Twenty-two human subjects with varying degrees of laser experience performed CO2
      laser surgical tasks within a simulated microlaryngeal operative setting using an
      industry standard manual micromanipulator (MMM) and a prototype robotic
      micromanipulator controller (RMC). Accuracy, repeatability, and ablation
      consistency measures were obtained for each human subject across both conditions
      and for the preprogrammed RMC device. RESULTS: Using the standard MMM, surgeons
      with >10 previous laser cases performed superior to subjects with fewer cases on
      measures of error percentage and cumulative error (P = .045 and .03,
      respectively). No significant differences in performance were observed between
      subjects using the RMC device. In the programmed (P/A) mode, the RMC performed
      equivalently or superiorly to experienced human subjects on accuracy and
      repeatability measures, and nearly an order of magnitude better on measures of
      ablation consistency. The programmed RMC performed significantly better for
      repetition error when compared to human subjects with <100 previous laser cases
      (P = .04). CONCLUSIONS: Experienced laser surgeons perform better than novice
      surgeons on tasks of accuracy and repeatability using the MMM device but roughly
      equivalently using the novel RMC. Operated in the P/A mode, the RMC performs
      equivalently or superior to experienced laser surgeons using the industry
      standard MMM for all measured parameters, and delivers an ablation consistency
      nearly an order of magnitude better than human laser operators. LEVEL OF
      EVIDENCE: NA.

PMID- 25582709
TI  - Sourcing of an alternative pericyte-like cell type from peripheral blood in
      clinically relevant numbers for therapeutic angiogenic applications.
AB  - Autologous cells hold great potential for personalized cell therapy, reducing
      immunological and risk of infections. However, low cell counts at harvest with
      subsequently long expansion times with associated cell function loss currently
      impede the advancement of autologous cell therapy approaches. Here, we aimed to
      source clinically relevant numbers of proangiogenic cells from an easy accessible
      cell source, namely peripheral blood. Using macromolecular crowding (MMC) as a
      biotechnological platform, we derived a novel cell type from peripheral blood
      that is generated within 5 days in large numbers (10-40 million cells per 100 ml
      of blood). This blood-derived angiogenic cell (BDAC) type is of monocytic origin,
      but exhibits pericyte markers PDGFR-beta and NG2 and demonstrates strong
      angiogenic activity, hitherto ascribed only to MSC-like pericytes. Our findings
      suggest that BDACs represent an alternative pericyte-like cell population of
      hematopoietic origin that is involved in promoting early stages of
      microvasculature formation. As a proof of principle of BDAC efficacy in an
      ischemic disease model, BDAC injection rescued affected tissues in a murine hind
      limb ischemia model by accelerating and enhancing revascularization. Derived from
      a renewable tissue that is easy to collect, BDACs overcome current short-comings
      of autologous cell therapy, in particular for tissue repair strategies.

PMID- 25582710
TI  - A new cell-penetrating peptide that blocks the autoinhibitory XIP domain of NCX1
      and enhances antiporter activity.
AB  - The plasma membrane Na(+)/Ca(2+) exchanger (NCX) is a high-capacity ionic
      transporter that exchanges 3Na(+) ions for 1Ca(2+) ion. The first 20 amino acids
      of the f-loop, named exchanger inhibitory peptide (XIP(NCX1)), represent an
      autoinhibitory region involved in the Na(+)-dependent inactivation of the
      exchanger. Previous research has shown that an exogenous peptide having the same
      amino acid sequence as the XIP(NCX1) region exerts an inhibitory effect on NCX
      activity. In this study, we identified another regulatory peptide, named P1,
      which corresponds to the 562-688aa region of the exchanger. Patch-clamp analysis
      revealed that P1 increased the activity of the exchanger, whereas the XIP
      inhibited it. Furthermore, P1 colocalized with NCX1 thus suggesting a direct
      binding interaction. In addition, site-directed mutagenesis experiments revealed
      that the binding and the stimulatory effect of P1 requires a functional XIP(NCX1)
      domain on NCX1 thereby suggesting that P1 increases the exchanger activity by
      counteracting the action of this autoinhibitory sequence. Taken together, these
      results open a new strategy for developing peptidomimetic compounds that, by
      mimicking the functional pharmacophore of P1, might increase NCX1 activity and
      thus exert a therapeutic action in those diseases in which an increase in NCX1
      activity might be helpful.

PMID- 25582712
TI  - Electromanipulating water flow in nanochannels.
AB  - In sharp contrast to the prevailing view that a stationary charge outside a
      nanochannel impedes water permeation across the nanochannel, molecular dynamics
      simulations show that a vibrational charge outside the nanochannel can promote
      water flux. In the vibrational charge system, a decrease in the distance between
      the charge and the nanochannel leads to an increase in the water net flux, which
      is contrary to that of the fixed-charge system. The increase in net water flux is
      the result of the vibrational charge-induced disruption of hydrogen bonds when
      the net water flux is strongly affected by the vibrational frequency of the
      charge. In particular, the net flux is reaches a maximum when the vibrational
      frequency matches the inherent frequency of hydrogen bond inside the nanochannel.
      This electromanipulating transport phenomenon provides an important new mechanism
      of water transport confined in nanochannels. 

PMID- 25582713
TI  - Chemodenervation for treatment of limb spasticity following spinal cord injury: a
      systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: To systematically review the
      literature on chemodenervation with botulinum toxin (BoNT) or phenol/alcohol for
      treatment of limb spasticity following spinal cord injury (SCI). SETTING: British
      Columbia, Canada. METHODS: EMBASE, MEDLINE, CINAHL, Cochrane Database of
      Systematic Reviews and Cochrane Central Register of Controlled Trials were
      searched for English language studies published up until March 2014. Studies were
      assessed for eligibility and quality by two independent reviewers. RESULTS: No
      controlled trials were identified. A total of 19 studies were included: 9
      involving BoNT and 10 involving phenol/alcohol. Owing to the clinically diverse
      nature of the studies, meta-analysis was deemed inappropriate. The studies
      produced level 4 and level 5 evidence that chemodenervation with BoNT or
      alcohol/phenol can lead to improvement in outcome measurements classified in the
      body structure and function, as well as activity domains of the International
      Classification of Functioning, Disability and Health framework. The Modified
      Ashworth Scale (MAS) was the most commonly used outcome measure. All six studies
      on BoNT and three of the four studies on phenol/alcohol measuring MAS reported a
      decrease in at least one point. An improvement in MAS was not always associated
      with improvement in function. The effect of phenol/alcohol has the potential to
      last beyond 6 months; study follow-up did not occur beyond this time point.
      CONCLUSION: Chemodenervation with BoNT or phenol/alcohol may improve spasticity
      and function in individuals with SCI. However, there is a lack of high-quality
      evidence and further research is needed to confirm the efficacy of these
      interventions.

PMID- 25582714
TI  - Hyponatremia in spinal cord injury patients: new insight into differentiating
      between the dilution and depletion forms.
AB  - STUDY DESIGN: This is a retrospective study. OBJECTIVES: The objectives of this
      study were to present a new model for differentiating between the dilution and
      depletion forms of hyponatremia in patients in the postacute phase after spinal
      cord injury (SCI), and to identify possible etiological factors contributing to
      hyponatremia in these patients. SETTING: University Hospital Motol, Prague, Czech
      Republic. METHODS: Eighty-seven of 352 patients hospitalized in 2008-2012 in the
      Spinal Cord Unit were hyponatremic. Seventy-four patients had SNa+=130-135 mmol
      l(-1) and 13 patients had SNa+ below 130 mmol l(-1). We propose a simple model of
      an electrolyte solution in which the Na(+) concentration is higher than the Cl(-)
      concentration, making it possible to compare the effects of dilution and
      depletion of Na(+) and Cl(-) on the Na(+) concentration. The depletion of Na(+)
      and Cl(-) leads to a significant increase in the Na(+)/Cl(-) ratio, with the
      Na(+)-Cl(-) value remaining unchanged. Dilution with water results in a decrease
      of Na(+)-Cl(-) with the Na(+)/Cl(-) ratio remaining unchanged. RESULTS: In
      patients with SNa+ below 130 mmol l(-1), hyponatremia was consistent with the
      depletion model in 46% and with the dilution model in 32%. In patients with SNa+
      ranging between 130 and 135 mmol l(-1), the respective rates were 34 and 12%.
      CONCLUSION: Examination of SNa+-SCl- and SNa+/SCl- in patients with SCI could be
      helpful in considering whether hyponatremia is consistent either with the NaCl
      dilution model or with the NaCl depletion model. Further studies are needed for
      more accurate interpretation of the results, particularly with respect to volume
      and acid-base disorders.

PMID- 25582717
TI  - [R'evolution in laboratory medicine: SFBC and Euromedlab'15].

PMID- 25582715
TI  - Evaluating perfusion of thoracic spinal cord blood using CEUS during thoracic
      spinal stenosis decompression surgery.
AB  - Study design:A clinical study in human spinal cord.Objectives:To evaluate changes
      in spinal cord blood perfusion in patients with thoracic spinal stenosis using
      contrast-enhanced ultrasonography and to semiquantitatively analyze blood
      perfusion changes in compressed spinal cord before and after ventral
      decompression.Setting:Ultrasound department of a university
      hospital.Methods:Twelve patients with confirmed thoracic spinal stenosis who
      needed decompression surgery participated. They underwent an intravenous
      injection of a contrast agent before and after ventral decompression.
      Quantitative analysis software (Philips Healthcare, Bothell, WA, USA) was used to
      perform time-intensity curve (TIC) analysis. The enhanced intensity (DeltaI),
      rise time (DeltaT) and slope of the TIC (beta) were separately calculated; t
      tests of the independent samples were performed on the indicators.Results:The
      TICs showed no significant differences between compressed spinal cord and normal
      spinal cord in DeltaT, enhanced DeltaI and beta (P= 0.46, P=0.23 and P=0.16,
      respectively). After ventral decompression, DeltaI of the originally compressed
      spinal cord increased substantially (P= 0.04) compared with DeltaI of the normal
      spinal cord; however, the DeltaT and beta showed no significant differences (P=
      0.18 and P=0.09, respectively). Comparison of the blood perfusion parameters
      (that is, DeltaT and DeltaI) of the compressed spinal cords before and after
      ventral decompression showed no significant differences (P=0.14 and P=0.12,
      respectively), but beta showed significant difference
      (P=0.02).Conclusion:Contrast-enhanced ultrasonography can dynamically display
      spinal cord blood perfusion. The characteristics of blood perfusion can be
      semiquantitatively analyzed using a software technique.Spinal Cord advance online
      publication, 13 January 2015; doi:10.1038/sc.2014.213.

PMID- 25582716
TI  - Thoracic spinal cord lesions are influenced by the degree of cervical spine
      involvement in multiple sclerosis.
AB  - STUDY DESIGN: Cross-sectional analyses. OBJECTIVE: To determine whether cervical
      spinal cord lesions predict the presence of thoracic cord lesions in multiple
      sclerosis (MS) patients. SETTING: Single MS Clinic, AZ, USA. METHODS: All MS
      patients, with MRI studies of the brain, cervical and thoracic spine obtained
      during a single scanning session, were acquired during a 1-year period. Clinical,
      demographic and imaging covariates were used in a multivariate regression model
      to refine predictors of thoracic cord involvement. RESULTS: A total of 687
      patients were evaluated, and patients were excluded because of a diagnosis of
      other neurological disorders, not meeting the 2010 McDonald criteria for MS
      (n=222) or incomplete neuraxis imaging (n=339). The study cohort comprised 126
      patients. There was an increase in the odds ratio (OR) of thoracic spine
      involvement when any cervical spine lesion was present (OR=6.08, 95% confidence
      interval (2.21-16.68), P<0.001). The multivariate logistic regression model
      demonstrated a substantial and significant increase in the odds of thoracic spine
      involvement when more than two cervical spine lesions were present, two lesions
      (OR 4.44, (0.91-21.60), P=0.06), three lesions (OR 19.76, (3.51-111.17),
      P=0.001), four or more lesions (OR 20.49, (1.97-213.23), P=0.012) and diffuse
      lesions (OR 71.94, (5.28-979.88), P=0.001), when adjusting for significant
      covariates including clinical symptoms, brain lesions, disease duration and
      treatment exposure. CONCLUSIONS: Thoracic spinal cord lesions appear to be
      predicated on the degree of cervical spine involvement in patients with MS, a
      risk that appears to be independent of brain findings or clinical features.

PMID- 25582718
TI  - [Mass spectrometry: from physics fundamentals to laboratory medicine].

PMID- 25582719
TI  - [Sample preparation and bioanalysis in mass spectrometry].
AB  - The quantitative analysis of compounds of clinical interest of low molecular
      weight (<1000 Da) in biological fluids is currently in most cases performed by
      liquid chromatography-mass spectrometry (LC-MS). Analysis of these compounds in
      biological fluids (plasma, urine, saliva, hair...) is a difficult task requiring
      a sample preparation. Sample preparation is a crucial part of chemical/biological
      analysis and in a sense is considered the bottleneck of the whole analytical
      process. The main objectives of sample preparation are the removal of potential
      interferences, analyte preconcentration, and converting (if needed) the analyte
      into a more suitable form for detection or separation. Without chromatographic
      separation, endogenous compounds, co-eluted products may affect a quantitative
      method in mass spectrometry performance. This work focuses on three distinct
      parts. First, quantitative bioanalysis will be defined, different matrices and
      sample preparation techniques currently used in bioanalysis by mass spectrometry
      of/for small molecules of clinical interest in biological fluids. In a second
      step the goals of sample preparation will be described. Finally, in a third step,
      sample preparation strategies will be made either directly ("dilute and shoot")
      or after precipitation.

PMID- 25582720
TI  - [Blood sampling using "dried blood spot": a clinical biology revolution
      underway?].
AB  - Blood testing using the dried blood spot (DBS) is used since the 1960s in
      clinical analysis, mainly within the framework of the neonatal screening (Guthrie
      test). Since then numerous analytes such as nucleic acids, small molecules or
      lipids, were successfully measured on the DBS. While this pre-analytical method
      represents an interesting alternative to classic blood sampling, its use in
      routine is still limited. We review here the different clinical applications of
      the blood sampling on DBS and estimate its future place, supported by the new
      methods of analysis as the LC-MS mass spectrometry. 

PMID- 25582721
TI  - [Mass spectrometry and clinical proteomics].
AB  - Proteomic analysis was promising from many years proposing new markers of
      pathologies and new targets for drug development. Constant progress in technics
      makes proteomics more efficient. This progress needs the development of mass
      spectrometers more precise on mass determination, more resolutive on ions
      separation, more sensitive for their detection, much more adapted to
      quantification of peaks, and with automated apparatus built for high throughput
      proteomics. MALDI-TOF keeps an important place in proteomics, as well as for low
      budget teams as for laboratories developing quantification and high throughput
      with TOF/TOF mode. ESI source is easy to couple to nanoLC, a good method for
      sequencing in bottom up strategy with quadripoles (Q), TOF or even with ionic
      traps in tandem. The analysis of post-translational modifications has become
      possible with most configurations of MS/MS coupling. Finally, electrophoresis
      keeps its place as an efficient method for separation, and chromatography is the
      source of constant technics progress. Proteomics has a bright future with
      multiple progresses in many technics. 

PMID- 25582722
TI  - [Some thoughts on the links between LC-MS/MS and therapeutic drug monitoring].
AB  - Therapeutic drug monitoring can be defined as a multiple step activity involving:
      (i) the measurement of a drug; (ii) the interpretation of the concentration by
      taking into account the concentration-effect relationship; (iii) the individual
      dose adjustment. For over 15 years pharmacology-toxicology departments have
      implemented liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)
      on a daily basis. This article discusses the current position of this technology
      in TDM routine activity. 

PMID- 25582723
TI  - [Clinical and analytical toxicology of opiate, cocaine and amphetamine].
AB  - In several circumstances, determination and quantification of illicit drugs in
      biological fluids are determinant. Contexts are varied such as driving under
      influence, traffic accident, clinical and forensic toxicology, doping analysis,
      chemical submission. Whole blood is the favoured matrix for the quantification of
      illicit drugs. Gas chromatography coupled with mass spectrometry (GC-MS) is the
      gold standard for these analyses. All methods developed must be at least
      equivalent to gas chromatography coupled with a mass spectrometer. Nowadays, new
      technologies are available to biologists and clinicians: liquid chromatography
      coupled with a mass spectrometry (LC/MS) or coupled with a tandem mass
      spectrometer (LC/MS/MS). The aim of this paper is to describe the state of the
      art regarding techniques of confirmation by mass spectrometry used for
      quantification of conventional drugs except cannabis. 

PMID- 25582724
TI  - [Mass spectrometry for steroid assays].
AB  - Steroid hormone measurement, first developed with radioimmunoassay, is now
      becoming easier with the use of automated platforms of immunoassay. However, some
      hormones remain uneasily detectable because of their low blood concentration,
      their structural homology or the presence of interferences. Liquid chromatography
      tandem mass spectrometry (LC-MS/MS) can be considered as an alternative to
      immunoassays. This approach allows the simultaneous determination of several
      parameters thanks to its selectivity led by the detector mass spectrometer and
      the separate dimension of chromatography liquid. In addition, recourse to UHPLC
      (ultra high performance liquid chromatography) allows improving selectivity and
      sensitivity while limiting the samples volumes. The "ready-to-use" kits are now
      available and added to the "homemade" techniques developed by laboratories, thus
      giving opportunity for measurement of a wide steroid panel with only one sample.
      Finally, mass spectrometry methods, including a prior extraction step, allow the
      use of varied biological fluids (blood, urine, saliva...). Also, several clinical
      indications could gain from mass spectrometry, especially when hormone levels are
      low, when several steroids have to be identified, when the sample volume is low.
      However, this technology represents an important financial investment and in
      depth staff training. In addition, some steroids are not easily quantifiable by
      mass spectrometry. It is likely by immunoassay and mass spectrometry, well
      matched technologies, that we could answer the best to clinical questions about
      steroids. 

PMID- 25582725
TI  - [Vitamin D measurement: pre-analytical and analytical considerations].
AB  - The constantly increasing requests for the measurement of serum 25-hydroxyvitamin
      D over the last years has led reagent manufacturers to market different automated
      and semi-automated methods, that being unfortunately not fully harmonized, yield
      different results. Liquid chromatography coupled to tandem mass spectrometry has
      more recently been introduced. This approach allows the distinction between the
      two forms of 25-hydroxyvitamin D and to measure other metabolites. This approach
      also requires harmonization to curtail the differences between the different
      analytical methods. To meet this requirement, the American national institutes of
      health (NIH), the CDC (Center for disease control and prevention) in Atlanta, the
      NIST (National institute of standards and technology) and the vitamin D Reference
      laboratory of Ghent University have pooled their expertise to develop a
      standardization program. This article reviews the main elements and the
      difficulties of the automated and semi-automated methods for 25-hydroxyvitamin D,
      from sample preparation to the analytical phase, as well as those related to mass
      spectrometry. It also addresses the issues related to the clinical decision
      thresholds and the possibility of measurements in different biological liquids. 

PMID- 25582726
TI  - [Mass spectrometry and inherited metabolic diseases diagnosis].
AB  - Tandem mass spectrometry is used for the diagnosis and following of metabolic
      disorders for acylcarnitine profiling and with liquide chromatography to explore
      creatin metabolism and amino and bile acids disorders. The analysis of organic
      acids by GC-MS is still the reference method for the diagnosis of inherited
      disorders of organiques acides and sterols. These techniques are also used to
      perform "in vitro" functional tests. 

PMID- 25582727
TI  - [Mass spectrometry and neonatal screening].
AB  - Tandem mass spectrometry allows to screen many inherited metabolic diseases
      within a single blood spot. It is possible to screen newborns for amino and
      organic acid, fatty acid oxidation disorders and lysosomal diseases. Tandem mass
      spectrometry neonatal screening is not yet realized in France in 2014. 

PMID- 25582728
TI  - [Mass spectrometry in bacteriology].
AB  - Recently, different bacteriological laboratory interventions that decrease
      reporting time have been developed. These promising new broad-based techniques
      have merit, based on their ability to identify rapidly many bacteria, organisms
      difficult to grow or newly emerging strains, as well as their capacity to track
      disease transmission. Maldi-TOF MS has been proven to be an accurate and reliable
      method for organism identification including bacteria, yeast, molds, and
      mycobacteria. It is rapid, with results often 24 hours earlier than traditional
      methods, and inexpensive. The range of applications of Maldi-TOF MS has been
      growing constantly, from rapid species identification to labor-intensive
      proteomic studies of bacterial physiology (bacterial resistance and virulence).
      The purpose of this review is to present the different solutions commercialized
      in France, summarize the place of this technology in microbiology lab and to
      analyze future perspectives in this field. 

PMID- 25582729
TI  - [Metabolome and mass spectrometry: new biomedical analysis perspectives].
AB  - Metabolomics is defined as an integrative approach consisting in the
      comprehensive analysis of all of the small molecules of a biological system (the
      "metabolome"). The main objective of metabolomics in medecine is to discover
      metabolic biomarkers for diseases. Mass spectrometry (MS) coupled to liquid or
      gas chromatography is amongst major analytical tools used in metabolomics.
      However, the holistic approach used in metabolomics requires very good
      performances of the analytical system (chromatographic column and MS equipment)
      and the use of non-conventional validation strategies. Metabolomics workflow can
      be divided in three main steps: sample preparation, MS data acquisition and
      processing, and statistical analysis. Processing of the "raw" data (obtained
      after MS acquisition) is mostly required to normalise chromatographic conditions
      and to carry out accurate quantification of MS features. Features resulting from
      this processing may be identified later. The statistical analyses include
      typically multivariate techniques such as supervised and non-supervised methods.
      Supervised methods make use of the response variable (e.g., case/control) for
      model construction while non-supervised methods do not use this piece of
      information. When the study is focused on a particular set of metabolites,
      targeted metabolomics could be an interesting alternative to the holistic
      approach since it may allow absolute quantitation and be associated with a
      reduced cost. 

PMID- 25582730
TI  - Scintigraphic tracking of mesenchymal stem cells after portal, systemic
      intravenous and splenic administration in healthy beagle dogs.
AB  - Mesenchymal stem cells have been proposed to treat liver disease in the dog. The
      objective of this study was to compare portal, systemic intravenous and splenic
      injections for administration of mesenchymal stem cells to target the liver in
      healthy beagle dogs. Four healthy beagle dogs were included in the study. Each
      dog received mesenchymal stem cells via all three delivery methods in randomized
      order, 1 week apart. Ten million fat-derived allogeneic mesenchymal stem cells
      labeled with Technetium-99m (99mTc)-hexamethyl-propylene amine oxime(HMPAO) were
      used for each injection. Right lateral, left lateral, ventral, and dorsal
      scintigraphic images were obtained with a gamma camera equipped with a low-energy
      all-purpose collimator immediately after injection and 1, 6, and 24 h later.
      Mesenchymal stem cells distribution was assessed subjectively using all four
      views. Pulmonary, hepatic, and splenic uptake was quantified from the right
      lateral view, at each time point. Portal injection resulted in diffuse
      homogeneous high uptake through the liver, whereas the systemic intravenous
      injection led to mesenchymal stem cell trapping in the lungs. After splenic
      injection, mild splenic retention and high homogeneous diffuse hepatic uptake
      were observed. Systemic injection of mesenchymal stem cells may not be a
      desirable technique for liver therapy due to pulmonary trapping. Splenic
      injection represents a good alternative to portal injection. Scintigraphic
      tracking with 99mTc-HMPAO is a valuable technique for assessing mesenchymal stem
      cells distribution and quantification shortly after administration. Data obtained
      at 24 h should be interpreted cautiously due to suboptimal labeling persistence. 

PMID- 25582732
TI  - The potential of resistant starch as a prebiotic.
AB  - Resistant starch is defined as the total amount of starch and the products of
      starch degradation that resists digestion in the small intestine. Starches that
      were able to resist the digestion will arrive at the colon where they will be
      fermented by the gut microbiota, producing a variety of products which include
      short chain fatty acids that can provide a range of physiological benefits. There
      are several factors that could affect the resistant starch content of a
      carbohydrate which includes the starch granule morphology, the amylose
      amylopectin ratio and its association with other food component. One of the
      current interests on resistant starch is their potential to be used as a
      prebiotic, which is a non-digestible food ingredient that benefits the host by
      stimulating the growth or activity of one or a limited number of beneficial
      bacteria in the colon. A resistant starch must fulfill three criterions to be
      classified as a prebiotic; resistance to the upper gastrointestinal environment,
      fermentation by the intestinal microbiota and selective stimulation of the growth
      and/or activity of the beneficial bacteria. The market of prebiotic is expected
      to reach USD 198 million in 2014 led by the export of oligosaccharides. Realizing
      this, novel carbohydrates such as resistant starch from various starch sources
      can contribute to the advancement of the prebiotic industry. 

PMID- 25582731
TI  - Analysis of late toxicity in nasopharyngeal carcinoma patients treated with
      intensity modulated radiation therapy.
AB  - PURPOSE: To observe the late toxicities in nasopharyngeal carcinoma (NPC)
      patients who achieved long-term survival after intensity modulated radiation
      therapy (IMRT). METHODS: 208 untreated NPC patients who received IMRT and
      survived more than five years with locoregional disease control and no metastasis
      were evaluated in this study. The prescription dose to the gross target volume of
      nasopharynx (GTVnx), positive neck lymph nodes (GTVnd), clinical target volume 1
      (CTV1) and 2 (CTV2) was 68Gy/30f, 60-66Gy/30f, 60 Gy/30f and 54Gy/30f,
      respectively. The nasopharynx and upper neck targets were irradiated using IMRT,
      and the lower neck and supraclavicular fossae targets were irradiated using the
      half-beam technique with conventional irradiation. The late toxicities were
      evaluated according to the LENT/SOMA criteria of 1995. RESULTS: The median follow
      up time was 78 months (60-96 months). The occurrence rates of cervical
      subcutaneous fibrosis, hearing loss, skin dystrophy, xerostomia, trismus,
      temporal lobe injury, cranial nerve damage, cataract, and brain stem injury
      induced by radiotherapy were 89.9%, 67.8%, 47.6%, 40.9%, 7.21%, 4.33%, 2.88%,
      1.44%, and 0.48%, respectively. No spinal cord injury and mandible damage were
      found. Grade 3-4 late injuries were observed as follows: 1 (0.48%) skin
      dystrophy, 4 (1.92%) cervical subcutaneous fibrosis, 2 (0.96%) hearing loss, 2
      (0.96%) cranial nerve palsy, and 1 (0.48%) temporal lobe necrosis. No grade 3-4
      late injuries occurred in parotid, temporomandibular joints and eyes. Xerostomia
      decreased gradually over time and then showed only slight changes after 4 years.
      The change in the incisor distance stabilised by 1 year after RT, however, the
      incidence of hearing loss, skin dystrophy, subcutaneous fibrosis and nervous
      system injuries increased over time after RT. CONCLUSION: The late injuries in
      most NPC patients who had long-term survivals after IMRT are alleviated. Within
      the 5 years of follow-up, we found xerostomia decreased gradually; The change in
      the incisor distance stabilised by 1 year after RT; while hearing loss, nervous
      system injuries increased over time after RT.

PMID- 25582733
TI  - In vitro propagation of Paphiopedilum orchids.
AB  - Paphiopedilum is one of the most popular and rare orchid genera. Members of the
      genus are sold and exhibited as pot plants and cut flowers. Wild populations of
      Paphiopedilum are under the threat of extinction due to over-collection and loss
      of suitable habitats. A reduction in their commercial value through large-scale
      propagation in vitro is an option to reduce pressure from illegal collection, to
      attempt to meet commercial needs and to re-establish threatened species back into
      the wild. Although they are commercially propagated via asymbiotic seed
      germination, Paphiopedilum are considered to be difficult to propagate in vitro,
      especially by plant regeneration from tissue culture. This review aims to cover
      the most important aspects and to provide an up-to-date research progress on in
      vitro propagation of Paphiopedilum and to emphasize the importance of further
      improving tissue culture protocols for ex vitro-derived explants. 

PMID- 25582734
TI  - Thermal imaging in screening of joint inflammation and rheumatoid arthritis in
      children.
AB  - Potential of modern thermal imaging for screening and differentiation of joint
      inflammation has not been assessed in child and juvenile patient populations,
      typically demanding groups in diagnostics of musculoskeletal disorders. We
      hypothesize that thermal imaging can detect joint inflammation in patients with
      juvenile idiopathic arthritis or autoimmune disease with arthritis such as
      systemic lupus erythematosus. To evaluate the hypothesis, we studied 58 children
      exhibiting symptoms of joint inflammation. First, the patients' joints were
      examined along clinical procedure supplemented with ultrasound imaging when
      deemed necessary by the clinician. Second, thermal images were acquired from
      patients' knees and ankles. Results of thermal imaging were compared to clinical
      evaluations in knee and ankle. The temperatures were significantly (pmax = 0.044,
      pmean < 0.001) higher in inflamed ankle joints, but not in inflamed knee joints.
      No significant difference was found between the skin surface temperatures of
      medial and lateral aspects of ankle joints. In knee joints the mean temperatures
      of medial and lateral aspect differed significantly (p = 0.004). We have
      demonstrated that thermal imaging may have potential for detecting joint
      inflammation in ankle joints of children. For knee joints our results are
      inconclusive and further research is warranted. 

PMID- 25582735
TI  - American college of gastroenterology monograph on the management of irritable
      bowel syndrome.
AB  - This editorial reviews a recently published guideline on management of irritable
      bowel syndrome. The guideline illustrates problems arising from the quality of
      clinical trials used in systematic reviews and the potential impact of the
      inherent weaknesses of those trials on rating the strength of evidence and the
      resulting recommendations. 

PMID- 25582736
TI  - The Role of Neoadjuvant Therapy in Characterizing Indeterminate Lung Lesions in
      Patients with Resectable Colorectal Liver Metastases.
AB  - BACKGROUND: Incidental pulmonary lesions are frequently found during the
      preoperative evaluation of patients considered for resection of colorectal liver
      metastases (CRLM), and their presence can confound management decisions. This
      study investigates the role of clinical and radiologic factors, including
      response to preoperative systemic chemotherapy, in determining the malignant
      probability of these lesions. METHODS: Computed tomography (CT) scans of 33
      patients with small (<=1 cm) lung lesions undergoing resection for CRLM after
      preoperative chemotherapy were reviewed. Radiological features were recorded from
      three sequential CT scans (baseline, postchemotherapy, and follow-up). Malignancy
      was diagnosed either by resection or serial imaging. Chemotherapy response
      comparing lung lesions and CRLM was categorized as: (1) concordant or (2)
      discordant. Chemotherapy response, imaging features, and other clinical factors
      were evaluated in multivariate analyses as predictors of malignancy. RESULTS:
      Among the 86 indeterminate lung lesions identified, 23 % (20/86) were found to be
      metastases on follow-up. Lesions 6-10 mm were more likely to be metastases (odds
      ratio [OR] = 3.14, p = 0.045), as were lesions located in the lower lobes (OR =
      4.50, p = 0.018). Concordant chemotherapy response was found in 13 of 86 (15 %)
      and was independently associated with metastatic disease (OR = 19.87, p < 0.001),
      with 11 of 13 (85 %) lesions determined to be metastases. In contrast, only 9 of
      73 lesions (12 %) with discordant response were found to be metastases.
      CONCLUSIONS: Lesion size, location, and chemotherapy response pattern were
      independent predictors of malignancy for patients with resectable CRLM and small
      indeterminate lung lesions. Utilization of preoperative chemotherapy can be a
      useful method of ruling out pulmonary metastases in these patients.

PMID- 25582737
TI  - Prognostic Impact of Preoperative Lymph Node Enlargement in Intrahepatic
      Cholangiocarcinoma: A Multi-Institutional Study by the Kyushu Study Group of
      Liver Surgery.
AB  - BACKGROUND: Although lymph node metastasis (LNM) has been considered an important
      prognostic factor for intrahepatic cholangiocarcinoma (ICC), the impact of lymph
      node enlargement on the prognosis of ICC, and the accuracy of diagnosis of LNM,
      have not been fully clarified. METHODS: Using a chart review of 225 patients with
      ICC, we compared survival times between patients with and without lymph node
      enlargement, and we evaluated the accuracy of diagnosis of LNM. We also performed
      a multivariate analysis to determine the variables affecting overall survival in
      the study population. RESULTS: The survival time of patients without lymph node
      enlargement was significantly longer than that of patients with lymph node
      enlargement (median survival time [MST] 43.7 vs. 20.1 months; p = 0.007).
      However, in the group with enlarged lymph nodes, survival time was prolonged as a
      result of hepatectomy (MST 20.1 vs. 7.6 months; p < 0.01). The sensitivity of
      lymph node size and positron emission tomography-computed tomography findings for
      diagnosing LNM were 50.0 % (23/46) and 31.2 % (5/16), respectively, and were thus
      insufficient. Multivariate analysis identified the serum carcinoembryonic antigen
      (hazard ratio [HR] 1.830) and carbohydrate antigen 19-9 (HR 2.189) levels, blood
      transfusion (HR 1.792), intrahepatic metastasis (HR 1.988), and final stage (HR
      8.684) as prognostic factors for overall survival, but lymph node enlargement was
      not identified as a prognostic factor. CONCLUSION: Preoperative evaluation of LNM
      proved to be difficult, and survival time in ICC patients with lymph node
      enlargement was prolonged as a result of hepatectomy. Thus, ICC patients with
      preoperative lymph node enlargement should not be prematurely deemed non-curative
      cases.

PMID- 25582738
TI  - Quality of Life in Platinum-Sensitive Recurrent Ovarian Cancer: Chemotherapy
      Versus Surgery Plus Chemotherapy.
AB  - PURPOSE: This study was designed to compare quality of life in a sample of
      Italian patients affected by platinum-sensitive recurrent ovarian cancer and
      submitted to chemotherapy alone or secondary cytoreductive surgery plus
      chemotherapy through validated questionnaires. METHODS: From January 2007 to
      December 2012, consecutive patients with suspicious recurrence of ovarian cancer,
      referred to the Division of Gynecologic Oncology at the University Campus Bio
      Medico of Rome, were assessed for this prospective, case-control study. After a
      diagnostic laparoscopy, surgical resectable patients were enrolled in group A
      (surgery plus chemotherapy). Patients not suitable for optimal debulking surgery
      and all patients who refused surgery were enrolled in group B (chemotherapy
      alone). At beginning of treatment, after the third and sixth cycle of
      chemotherapy, all eligible patients were asked to fill in QLQ-C30 (version 3.0)
      and EORTC QLQ-OV28 questionnaires. RESULTS: Group A included 38 patients and
      underwent SCS followed by chemotherapy; group B included 16 patients that were
      submitted to chemotherapy alone. Quality-of-life scores of both questionnaires
      were comparable between groups, with the exception of constipation and pain,
      which resulted significantly worsened in Group A at 3 months. This difference was
      no longer present at 6 months. Median overall survival was 72 % for Group A and
      56 % in Group B at median follow-up of 35 months for Group A and 32 months for
      Group B. CONCLUSIONS: Both surgery followed by chemotherapy and chemotherapy
      alone seem to have a negligible impact on QOL. SCS plus chemotherapy seems to be
      an effective and tolerable therapeutic option in platinum-sensitive recurrences.

PMID- 25582741
TI  - The role of U.S. cancer centers in global cancer care.

PMID- 25582739
TI  - Surgical Referral for Colorectal Liver Metastases: A Population-Based Survey.
AB  - BACKGROUND: Surgical resection is underutilized for patients with colorectal
      liver metastases (CLM). Although the causes of underutilization are poorly
      understood, provider attitudes towards surgical referral may be contributory. We
      sought to understand medical oncologists' perspectives on referral for CLM.
      METHODS: Medical oncologists who treat colorectal cancer in the US state of
      Michigan were surveyed. We characterized respondents' attitudes regarding
      clinical and tumor-related contraindications to liver resection for CLM, as well
      as referral and treatment preferences using case-based scenarios. We then
      evaluated practice characteristics and treatment preferences between physicians.
      RESULTS: A total of 112 eligible responses were received (46 % response rate).
      Nearly 40 % of respondents reported having no liver surgeons in their practice
      area. Commonly perceived contraindications to liver resection included
      extrahepatic disease (80.3 %), poor performance status (77.7 %), the presence of
      >4 metastases (62.5 %), bilobar metastases (43.8 %), and metastasis size >5 cm
      (40.2 %). Compared with high-referring physicians, low-referring physicians were
      just as likely to refer a patient with very low recurrence risk (89.3 vs. 98.3 %;
      p = 0.099), but much less likely to refer a patient with moderate risk (0 vs.
      82.8 %; p < 0.001). High-referring physicians were more likely to consider
      resection for scenarios consistent with higher recurrence risk (31.0 vs. 10.7 %;
      p = 0.05). CONCLUSIONS: We found wide variation in surgical referral patterns for
      CLM. Many felt that bilobar disease and tumor size were contraindications to
      liver-directed therapy despite a lack of supporting data. These findings suggest
      an urgent need to increase dissemination of evidence and guidance regarding
      management for CLM, perhaps through increased specialist participation in tumor
      boards.

PMID- 25582740
TI  - Improved Survival with Anti-VEGF Therapy in the Treatment of Unresectable
      Appendiceal Epithelial Neoplasms.
AB  - BACKGROUND: Currently, cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy are accepted treatments for surgically resectable appendiceal
      epithelial neoplasms. However, for nonsurgical candidates, systemic treatment may
      be considered. The purpose of this analysis was to determine the benefit of
      biologic therapy (anti-vascular endothelial growth factor and anti-epidermal
      growth factor receptor) in addition to systemic chemotherapy in this select
      patient population. METHODS: The MD Anderson Cancer Center tumor registry was
      retrospectively reviewed for systemic treatment-naive appendiceal epithelial
      neoplasm patients registered between January 2000 to July 2007 for prior
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy status,
      histologic grade, signet ring pathology, systemic chemotherapy, biologic therapy,
      tumor markers (carcinoembryonic antigen, carbohydrate antigen [CA] 125, and/or
      CA19-9), progression-free survival (PFS), overall survival (OS), and disease
      control rate. Kaplan-Meier method, log-rank, and Cox proportional hazard
      regression models were used for statistical analysis. RESULTS: A total of 353
      patients were identified; 130 patients met the inclusion criteria. Fifty-nine
      patients received biologic therapy. The use of the anti-vascular endothelial
      growth factor (VEGF) agent bevacizumab improved both OS (42 months vs. 76 months,
      hazard ratio 0.49 [95 % confidence interval 0.25-0.94] P = 0.03) and PFS (4
      months vs. 9 months, hazard ratio 0.69 [95 % confidence interval 0.47-0.995], P =
      0.047) for all histologic subtypes. Moderately differentiated tumors had an
      improved PFS relative to well-differentiated tumors, 9 months versus 3 months (P
      = 0.05). CONCLUSIONS: Bevacizumab in combination with chemotherapy appears to
      play a role in surgically unresectable appendiceal epithelial neoplasm patients,
      with an improvement in PFS and OS. Anti-VEGF agents should be strongly considered
      in the management of patients with higher-grade appendiceal epithelial neoplasms
      who are suboptimal candidates for surgical resection.

PMID- 25582742
TI  - Global surgical oncology disease burden: addressing disparities via global
      surgery initiatives: the University of Michigan International Breast Cancer
      Registry.
AB  - BACKGROUND: Disparities in breast cancer incidence and outcome between African
      American and white American women are multifactorial in etiology. The increased
      frequency of triple-negative breast cancers (TNBC) in African American patients
      suggests the possible contribution of hereditary factors related to African
      ancestry. METHODS: The University of Michigan (UM)-Komfo Anoyke Teaching Hospital
      (KATH) Breast Cancer Research Collaborative and International Breast Registry was
      established in 2004. It features epidemiologic information, tumor tissue, and
      germline DNA specimens from African American, white American, and Ghanaian women.
      RESULTS: This research collaborative has generated valuable findings regarding
      the pathogenesis and patterns of TNBC while concomitantly improving the standard
      of breast oncology care in Ghana. This partnership has also yielded important
      opportunities for academic and educational exchange. It has expanded to involve
      other sites in Africa and Haiti. CONCLUSIONS: The UM-KATH collaborative is a
      model for demonstrating the research and academic exchange value of international
      partnerships.

PMID- 25582743
TI  - Validation of hepatectomy for elderly patients with hepatocellular carcinoma.
AB  - BACKGROUND: The safety and feasibility of hepatectomy for hepatocellular
      carcinoma (HCC) in the elderly population have not been defined to date. METHODS:
      A single-center, retrospective cohort study was conducted with 104 patients who
      underwent hepatectomy for HCC from 2005 to 2010. The patients were divided into
      two groups, the elderly group (age, >=75 years; n = 22) and the nonelderly group
      (age, <75 years; n = 82), for comparison of short- and long-term outcomes.
      RESULTS: More patients were categorized as preoperative Eastern Cooperative
      Oncology Group (ECOG) performance status 1 in the elderly group (32 %) than in
      the nonelderly group (6 %) (P = 0.003). Complications with a Clavien-Dindo
      classification of grade 3a or higher were more frequently observed in the elderly
      group (41 %) than in the nonelderly group (17 %) (P = 0.006). Multivariate
      logistic regression showed ECOG performance status 1 as the only independent
      predictor of complications classified as Clavien-Dindo grade 3a or higher. The in
      hospital mortality rates were similar between the two groups (P = 0.20). During a
      median follow-up period of 47 months, the unadjusted 5-year recurrence-free
      survival rates were similar in the elderly (25 %) and nonelderly (33 %) groups (P
      = 0.80). Multiple tumors and high alpha-fetoprotein levels emerged as independent
      negative indicators of recurrence-free survival using multivariate Cox analyses.
      The adjusted risk for recurrence was not elevated in the elderly group (hazard
      ratio [HR], 0.92; 95 % confidence interval [CI] 0.50-1.68; P = 0.78).
      CONCLUSIONS: Despite the more frequent occurrence of complications with a Clavien
      Dindo grade of 3a or higher among the elderly patients undergoing hepatectomy for
      HCC, their mortality and recurrence rates were comparable with those of the
      nonelderly patients. Therefore, age alone is not a determinant of surgical
      candidacy for HCC.

PMID- 25582744
TI  - Patterns of Recurrence in Patients with Stage IIIB/C Cutaneous Melanoma of the
      Head and Neck Following Surgery With and Without Adjuvant Radiation Therapy: Is
      Isolated Regional Recurrence Salvageable?
AB  - BACKGROUND: Understanding recurrence patterns is vital for guiding treatment.
      This study describes recurrence patterns for patients with stage IIIB/C head and
      neck melanoma (HNM) after therapeutic lymph node dissection (TLND) +/- adjuvant
      radiation therapy (RT). We also report outcomes for salvage therapy for patients
      with isolated regional relapse. METHODS AND MATERIALS: A single-institution
      prospective database of 173 patients with American Joint Committee on Cancer
      (AJCC) stage IIIB/C HNM undergoing TLND between 1997 and 2012 was retrospectively
      reviewed. Timing and patterns of recurrence were reviewed. Univariable and
      multivariable analyses were undertaken using the Kaplan-Meier and Cox regression
      methods to determine factors predictive of recurrence. Median follow-up was 32
      months. RESULTS: Adjuvant RT was administered to 66/173 (38 %) patients. Patients
      selected for RT had a higher AJCC stage and had more extracapsular invasion. The
      5-year distant, cervical nodal and in-transit recurrence rates were 38, 10, and
      13 %, respectively, following surgery alone compared with 60, 17, and 31 %,
      respectively, for the adjuvant RT group. The head and neck regional 5-year
      recurrence rate (combining in-basin nodal and in-transit) was 23 % for the entire
      cohort. Isolated cervical recurrence occurred in 19 patients: 17/19 underwent
      salvage surgery (10/17 patients received RT after salvage surgery) and 2/19 had
      RT alone. However, distant recurrence occurred in 12/19 salvage patients, with
      most occurring within 12 months, while 4/19 were disease free. CONCLUSIONS: Using
      a selective approach for adjuvant RT, isolated cervical recurrence after TLND is
      uncommon. Isolated cervical recurrence can be salvaged effectively with further
      local therapy; however, distant disease frequently follows.

PMID- 25582746
TI  - Early (<10 mm) HER2-Positive Invasive Breast Carcinomas are Associated with
      Extensive Diffuse High-Grade DCIS: Implications for Preoperative Mapping, Extent
      of Surgical Intervention, and Disease-Free Survival.
AB  - BACKGROUND: The few publications on <10-mm invasive breast carcinomas have
      reported worse outcomes for women with human epidermal growth factor receptor 2
      (HER2)-positive cancer compared with HER2-negative cases and indicated that the
      high risk of recurrence in HER2-positive cases is related to the high grade,
      hormone receptor negativity, and high proliferation index of the invasive tumor
      component. METHODS: We studied the subgross morphology of such tumors in a
      consecutive series of 203 cases documented in large-format histology slides and
      worked up with detailed radiological-pathological correlation. RESULTS: The
      invasive component was associated with a diffuse in situ component in 78 % of the
      HER2-positive and 26 % of HER2-negative tumors <10 mm in size (odds ratio [OR],
      11.3936; P < .0001). The in situ component was of high grade in 75 % of HER2
      positive and 9 % of HER2-negative cases (OR, 29.6000; P < .0001). Significant
      associations were also found between the HER2 positivity of the invasive
      component and diffuse combined lesion distribution (P > .0001), invasive tumor
      grade 3 (P = .0004), presence of vascular invasion (P = .0026), extensive disease
      (P = .0170), "not special" (ductal) histological tumor type (P = .0302), estrogen
      receptor negativity (OR, 7.8846; P < .0001), and high Ki67 proliferation index
      (OR, 5.0000; P = .0007). The HER2-positive tumors tended to be multifocal (OR,
      2.000) and lymph node-positive (OR, 3.0147), but the tendency was not
      statistically significant. CONCLUSIONS: The vast majority of <10-mm HER2-positive
      breast carcinomas exhibited a high-grade, diffuse, and extensive in situ
      component, which may explain the high risk of recurrence among these tumors.

PMID- 25582745
TI  - Positive postoperative CEA is a strong predictor of recurrence for patients after
      resection for colorectal liver metastases.
AB  - BACKGROUND: The role of carcinoembryonic antigen (CEA) in surveillance and follow
      up of patients with colorectal cancer continues to be debated. The objective of
      this study was to assess the utility of postoperative CEA as a predictor of
      recurrence for patients with resected colorectal liver metastases (CLM). METHODS:
      Patients were identified from a prospectively maintained CLM database, and were
      studied retrospectively. Patients with extrahepatic disease or initially
      unresectable CLM were excluded. All patients in this study received adjuvant
      systemic chemotherapy after resection. RESULTS: Between 1997 and 2007, a total of
      318 consecutive patients were studied, with 168 patients (53 %) experiencing
      recurrence within 2 years. Various postoperative CEA cutoffs were tested as
      independent predictors of recurrence. A postoperative CEA >=15 ng/ml obtained the
      highest hazard ratio (1.87; 95 % CI 1.09-3.2; p = 0.023) and was chosen to be
      included in the survival analysis in the multivariate model. A postoperative CEA
      >=15 ng/ml had a specificity of 96 % and positive predictive value of 82 % for
      recurrence. On multivariate analysis, age >=70 years, the presence of positive
      lymph node at primary tumor resection, disease-free interval <=12 months, number
      of lesions >1, largest lesion >=5 cm, presence of positive margins, and
      postoperative CEA >=15 ng/ml were independent predictors of recurrence within 2
      years. CONCLUSION: This study demonstrates a postoperative CEA >=15 ng/ml to be a
      predictive test for recurrence.

PMID- 25582747
TI  - Mesothelioma in Mongolia: case report.
AB  - BACKGROUND: More than 80% of cases of mesothelioma worldwide have a history of
      asbestos exposure. In Mongolia, workers in coal burning thermal power plants
      (TPP) have widely utilized asbestos as an insulation material. METHODS: We
      describe the case of a 47-year-old woman diagnosed with a malignant pleural
      mesothelioma. She worked in a TPP in Ulaanbaatar, Mongolia for 28 years. RESULTS:
      A computer tomography (CT) scan showed a circumferential ring around her left
      lung, and tissues' samples had a biphasic variant of mesothelioma with
      epithelioid and sarcomatoid components. DISCUSSION: This is the first reported
      case of mesothelioma in Mongolia. We expect additional cases of mesothelioma, as
      well as other asbestos related diseases, will be identified in the future. In
      order to properly track asbestos related diseases in the country, we recommend
      the creation of an asbestos related disease registry.

PMID- 25582748
TI  - Diffuse pleural thickening following heart failure-related pleural effusions in
      an asbestos exposed patient.
AB  - Diffuse pleural thickening (DPT) is a well-recognized consequence of asbestos
      exposure and often follows a benign asbestos-related pleural effusion. At our
      tertiary center, in the North West of England where the prevalence of asbestos
      related pleural disease is high, we have encountered a series of patients that
      have had led us to consider a new hypothesis in DPT. We postulate that non
      asbestos-related pleural effusions, particularly transudative pleural effusions,
      caused by heart failure can trigger the development of DPT. We present one such
      case, discuss the limitations of our temporal observations, and invite further
      discussions from readers. 

PMID- 25582749
TI  - Neural stem cell transplantation enhances mitochondrial biogenesis in a
      transgenic mouse model of Alzheimer's disease-like pathology.
AB  - Mitochondrial dysfunction, especially a defect in mitochondrial biogenesis, is an
      early and prominent feature of Alzheimer's disease (AD). Previous studies
      demonstrated that the number of mitochondria is significantly reduced in
      susceptible hippocampal neurons from AD patients. Neural stem cell (NSC)
      transplantation in AD-like mice can compensate for the neuronal loss resulting
      from amyloid-beta protein deposition. The effects of NSC transplantation on
      mitochondrial biogenesis and cognitive function in AD-like mice, however, are
      poorly understood. In this study, we injected NSCs or vehicle into 12-month-old
      amyloid precursor protein (APP)/PS1 transgenic mice, a mouse model of AD-like
      pathology. The effects of NSC transplantation on cognitive function, the amount
      of mitochondrial DNA, the expression of mitochondrial biogenesis factors and
      mitochondria-related proteins, and mitochondrial morphology were investigated.
      Our results show that in NSC-injected APP/PS1 (Tg-NSC) mice, the cognitive
      function, number of mitochondria, and expression of mitochondria-related
      proteins, specifically the mitochondrial fission factors (dynamin-related protein
      1 [Drp1] and fission 1 [Fis1]) and the mitochondrial fusion factor optic atrophy
      1 (OPA1), were significantly increased compared with those in age-matched vehicle
      injected APP/PS1 (Tg-Veh) mice, whereas the expression of mitochondrial fusion
      factors mitofusion 1 (Mfn1) and Mfn2 was significantly decreased. These data
      indicate that NSC transplantation may enhance mitochondria biogenesis and further
      rescue cognitive deficits in AD-like mice. 

PMID- 25582750
TI  - Identification of stage-specific markers during differentiation of hair cells
      from mouse inner ear stem cells or progenitor cells in vitro.
AB  - The induction of inner ear hair cells from stem cells or progenitor cells in the
      inner ear proceeds through a committed inner ear sensory progenitor cell stage
      prior to hair cell differentiation. To increase the efficacy of inducing inner
      ear hair cell differentiation from the stem cells or progenitor cells, it is
      essential to identify comprehensive markers for the stem cells/progenitor cells
      from the inner ear, the committed inner ear sensory progenitor cells and the
      differentiating hair cells to optimize induction conditions. Here, we report that
      we efficiently isolated and expanded the stem cells or progenitor cells from
      postnatal mouse cochleae, and induced the generation of inner ear progenitor
      cells and subsequent differentiation of hair cells. We profiled the gene
      expression of the stem cells or progenitor cells, the inner ear progenitor cells,
      and hair cells using aRNA microarray analysis. The pathway and gene ontology (GO)
      analysis of differentially expressed genes was performed. Analysis of genes
      exclusively detected in one particular cellular population revealed 30, 38, and
      31 genes specific for inner ear stem cells, inner ear progenitor cells, and hair
      cells, respectively. We further examined the expression of these genes in vivo
      and determined that Gdf10+Ccdc121, Tmprss9+Orm1, and Chrna9+Espnl are marker
      genes specific for inner ear stem cells, inner ear progenitor cells, and
      differentiating hair cells, respectively. The identification of these marker
      genes will likely help the effort to increase the efficacy of hair cell induction
      from the stem cells or progenitor cells. 

PMID- 25582751
TI  - BAP1 regulates cell cycle progression through E2F1 target genes and mediates
      transcriptional silencing via H2A monoubiquitination in uveal melanoma cells.
AB  - Uveal melanoma (UM) is the most common form of primary intraocular malignancy in
      adult and has the tendency to metastasize. BAP1 mutations are frequently found in
      UM and are associated with a poor prognosis. The role of BAP1 in cell cycle
      regulation is currently a research highlight, but its underlying mechanism is not
      well understood. Here, we report that BAP1 knockdown can lead to G1 arrest and is
      accompanied by a decrease in the expression of S phase genes in OCM1 cells.
      Furthermore, in chromatin immunoprecipitation experiments, BAP1 could bind to
      E2F1 responsive promoters and the localization of BAP1 to E2F1-responsive
      promoters is host cell factor-1 dependent. Moreover, BAP1 knockdown leads to
      increased H2AK119ub1 levels on E2F responsive promoters. Together, these results
      provide new insight into the mechanisms of BAP1 in cell cycle regulation. 

PMID- 25582752
TI  - Effects of dietary fermentation concentrate of Hericium caput-medusae (Bull.:Fr.)
      Pers. on growth performance, digestibility, and intestinal microbiology and
      morphology in broiler chickens.
AB  - BACKGROUND: The present study was undertaken to investigate the effects of
      fermentation concentrate of Hericium caput-medusae (Bull.:Fr.) Pers. (HFC) on
      growth performance, digestibility, intestinal microbiology, and intestinal
      morphology in broiler chickens. A total of 600 male Arbor Acres broilers were
      randomly divided into five dietary treatments (20 broilers per pen with six pens
      per treatment): CON (basal diet), ANT (basal diet supplemented with 5 mg kg(-1)
      flavomycin) and HFC (basal diet supplemented with 6, 12, and 18 g kg(-1) HFC).
      The experimental lasted for 42 days. RESULTS: The results revealed that the
      average daily gain [linear (L), P < 0.01; quadratic (Q), P < 0.01] of broilers
      increased when the HFC levels increased during the starter (days 1-21), finisher
      (days 22-42), and the overall experiment period (days 1 to 42). In the small
      intestinal digesta and the caecum digesta, the Escherichia coli count (L, P <
      0.05; Q, P < 0.001) decreased while the Lactobacilli count (L, P < 0.01; Q, P <
      0.001) and Bifidobacteria count (L, P < 0.001; Q, P < 0.001) increased when the
      HFC levels increased. The crude protein digestibility of broilers (L, P < 0.01;
      Q, P < 0.001) increased when the HFC levels increased. In the duodenum, jejunum,
      and ileum of broilers, the villus height and villus height to crypt depth ratio
      (L, P < 0.001; Q, P < 0.001) increased when the HFC levels increased. CONCLUSION:
      Dietary supplementation with HFC increased gut Lactobacilli and Bifidobacteria
      counts and inhibited E. coli growth, improved nutrient utilisation and intestine
      villus structure, and thus improved the growth of broilers.

PMID- 25582753
TI  - Expression of the functional recombinant human glycosyltransferase GalNAcT2 in
      Escherichia coli.
AB  - BACKGROUND: Recombinant protein-based therapeutics have become indispensable for
      the treatment of many diseases. They are produced using well-established
      expression systems based on bacteria, yeast, insect and mammalian cells. The
      majority of therapeutic proteins are glycoproteins and therefore the post
      translational attachment of sugar residues is required. The development of an
      engineered Escherichia coli-based expression system for production of human
      glycoproteins could potentially lead to increased yields, as well as significant
      decreases in processing time and costs. RESULTS: This work describes the
      expression of functional human-derived glycosyltransferase UDP-GalNAc:polypeptide
      N-acetylgalactosaminyltransferase 2 (GalNAcT2) in a recombinant E. coli strain.
      For expression, a codon-optimised gene encoding amino acids 52-571 of GalNAcT2
      lacking the transmembrane N-terminal domain was inserted into a pET-23 derived
      vector encoding a polyhistidine-tag which was translationally fused to the N
      terminus of the glycosyltransferase (HisDapGalNAcT2). The glycosyltransferase was
      produced in E. coli using a recently published expression system. Soluble
      HisDapGalNAcT2 produced in SHuffle(r) T7 host cells was purified using nickel
      affinity chromatography and was subsequently analysed by size exclusion
      chromatography coupled to multi-angle light scattering (SEC-MALS) and circular
      dichroism spectroscopy to determine molecular mass, folding state and thermal
      transitions of the protein. The activity of purified HisDapGalNAcT2 was monitored
      using a colorimetric assay based on the release of phosphate during transfer of
      glycosyl residues to a model acceptor peptide or, alternatively, to the
      granulocyte-colony stimulating growth factor (G-CSF). Modifications were assessed
      by Matrix Assisted Laser Desorption Ionization Time-of-flight Mass Spectrometry
      analysis (MALDI-TOF-MS) and Electrospray Mass Spectrometry analysis (ESI-MS). The
      results clearly indicate the glycosylation of the acceptor peptide and of G-CSF.
      CONCLUSION: In the present work, we isolated a human-derived glycosyltransferase
      by expressing soluble HisDapGalNAcT2 in E. coli. The functional activity of the
      enzyme was shown in vitro. Further investigations are needed to assess the
      potential of in vivo glycosylation in E. coli.

PMID- 25582754
TI  - Look back for the Charlson Index did not improve risk adjustment of cancer
      surgical outcomes.
AB  - OBJECTIVES: The Charlson score is a commonly used measure of comorbidity;
      however, there is little empirical research into the optimal implementation when
      studying cancer surgery outcomes using administrative data. We compared four
      alternative Charlson score implementations, including and excluding metastatic
      cancer and varying the look-back periods. STUDY DESIGN AND SETTING: Nine years of
      linked administrative data were used to identify patients undergoing surgery for
      cancer of the colon, rectum, or lung in New South Wales, Australia. Four binary
      outcomes of 30- and 365-day mortality, length of stay greater than 21 days, and
      emergency readmission within 28 days were compared between groups of similar
      hospitals. Hospital risk adjustment models were compared for alternative Charlson
      score implementations. RESULTS: Excluding metastatic cancer from the Charlson
      score improved model performance for short-term outcomes, but there was no
      implementation that was consistently optimal. Incorporating a look-back period
      reduced the number of patients for analysis but did not improve hospital risk
      adjustment. CONCLUSION: Charlson scores for hospital risk adjustment of short
      term outcomes of cancer surgery should be calculated excluding metastatic cancer
      as a separate comorbidity. We found no clear best performing implementation and
      found no benefit in incorporating any look-back period.

PMID- 25582756
TI  - A 2-year follow-up study of patients participating in our transcranial pulsating
      electromagnetic fields augmentation in treatment-resistant depression.
AB  - OBJECTIVE: We have made a 2-year follow-up study to evaluate the effect of
      repeated transcranial pulsating electromagnetic fields (T-PEMF) augmentation in
      patients who had achieved remission but later on relapsed, as well as to identify
      factors contributing to treatment-resistant depression in patients who did not
      respond to T-PEMF. METHODS: Using the Longitudinal Expert Assessment of All Data
      approach the patients were classified in four groups: A: patients who achieved
      remission; B: patients with doubtful effect; C: patients with no effect; and D:
      patients who were hard-to-assess. RESULTS: In group A, comprising 27 patients, 13
      had relapsed; they obtained a clear remission after a repeated course of T-PEMF
      augmentation. In group D, comprising 16 patients, we identified misdiagnostic
      factors both concerning the event of remission after the previous T-PEMF
      augmentation and concerning the aetiology (psychosocial stressors and co-morbid
      conditions). Compared with the other groups, the group D patients had a smaller
      number of previous episodes (p=0.09) and a longer duration of the current episode
      (p=0.01). CONCLUSION: T-PEMF has an effect among patients who relapsed after
      remission with the first series of T-PEMF. Treatment-resistant depression is a
      condition that has a high degree of multivariate problems. Misuse of alcohol or
      drugs, severe somatic disorders and other psychosocial problems may need other
      kinds of treatment before T-PEMF augmentation.

PMID- 25582755
TI  - Elderly onset intramedullary epidermoid cyst in the conus medullaris: a case
      report.
AB  - INTRODUCTION: Epidermoid cysts are known as embryonic or acquired ectopic
      aberrations of the ectoderm. To the best of our knowledge, there are only a few
      reports of elderly onset intramedullary epidermoid cysts. We report a case of
      elderly onset intramedullary epidermoid cyst at the conus medullaris. CASE
      PRESENTATION: A 63-year-old Japanese woman working as a farmer presented with
      slowly progressive gait disturbance and voiding dysfunction. A magnetic resonance
      imaging scan revealed an intramedullary mass lesion at L1 to L3. We diagnosed the
      lesion as an intramedullary spinal cord tumor. A laminectomy was performed at the
      level of Th12 to L3. Upon spinal cord dissection, a yellowish milky exudation
      erupted from the cystic lesion. We resected white cartilage-like pieces from the
      cystic cavity. Because the wall of the cystic lesion tightly adhered to the
      spinal cord parenchyma, we abandoned complete resection of the cyst wall. The
      pathological diagnosis was an epidermoid cyst. CONCLUSIONS: We propose that
      evacuation of the cyst contents is preferable, especially in cases with elderly
      onset and congenital origin.

PMID- 25582757
TI  - Triesterase and promiscuous diesterase activities of a di-Co(II)-containing
      organophosphate degrading enzyme reaction mechanisms.
AB  - The reaction mechanism for the hydrolysis of trimethyl phosphate and of the
      obtained phosphodiester by the di-Co(II) derivative of organophosphate degrading
      enzyme from Agrobacterium radiobacter P230(OpdA), have been investigated at
      density functional level of theory in the framework of the cluster model
      approach. Both mechanisms proceed by a multistep sequence and each catalytic
      cycle begins with the nucleophilic attack by a metal-bound hydroxide on the
      phosphorus atom of the substrate, leading to the cleavage of the phosphate-ester
      bond. Four exchange-correlation functionals were used to derive the potential
      energy profiles in protein environments. Although the enzyme is confirmed to work
      better as triesterase, as revealed by the barrier heights in the rate-limiting
      steps of the catalytic processes, its promiscuous ability to hydrolyze also the
      product of the reaction has been confirmed. The important role played by water
      molecules and some residues in the outer coordination sphere has been elucidated,
      while the binuclear Co(II) center accomplishes both structural and catalytic
      functions. To correctly describe the electronic configuration of the d shell of
      the metal ions, high- and low-spin arrangement jointly with the occurrence of
      antiferromagnetic coupling, have been herein considered. 

PMID- 25582759
TI  - Efficacy of statins on sirtuin 1 and endothelial nitric oxide synthase
      expression: the role of sirtuin 1 gene variants in human coronary
      atherosclerosis.
AB  - Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and are
      used to reduce the risk of coronary artery disease (CAD) due to their pleiotropic
      effects. Recently, greater focus has been placed on the role of sirtuin 1 (SIRT1)
      in cardiovascular disease research. However, insufficient data exist on the
      relationships between statins, SIRT1 protein levels, and SIRT1 gene variants. In
      the present study, we investigated the effects of statins, atorvastatin and
      rosuvastatin, in CAD patients by analysing the associations between SIRT1 gene
      variants, rs7069102C>G and rs2273773C>T, and SIRT1/endothelial nitric oxide
      (eNOS) expression, as well as total antioxidant and oxidant status, and the
      oxidative stress index. SIRT1 expression was significantly higher, and eNOS
      expression was significantly lower in CAD patients when compared with controls.
      Statin treatment reduced SIRT1 expression and increased eNOS expression, similar
      to the levels found in the control population, independent from the studied SIRT1
      gene variants. Oxidative stress parameters were significantly increased in CAD
      patients, and were decreased by statin treatment, demonstrating the antioxidative
      effects of statins on atherosclerosis. These results indicate that statin
      treatment could produce its protective effect on cardiovascular disease through
      the inhibition of SIRT1 expression. This is the first study reporting on the
      effect of statins, specifically atorvastatin and rosuvastatin, on SIRT1
      expression in CAD patients.

PMID- 25582761
TI  - Pharmacokinetics and effects on thromboxane B2 production following intravenous
      administration of flunixin meglumine to exercised thoroughbred horses.
AB  - Flunixin meglumine is commonly used in horses for the treatment of
      musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL
      when administered at least 24 h prior to race time. In light of samples exceeding
      the regulatory threshold at 24 h postadministration, the primary goal of the
      study reported here was to update the pharmacokinetics of flunixin following
      intravenous administration, utilizing a highly sensitive liquid chromatography
      mass spectrometry (LC-MS). An additional objective was to characterize the
      effects of flunixin on COX-1 and COX-2 inhibition when drug concentrations
      reached the recommended regulatory threshold. Sixteen exercised adult horses
      received a single intravenous dose of 1.1 mg/kg. Blood samples were collected up
      to 72 h postadministration and analyzed using LC-MS. Blood samples were collected
      from 8 horses for determination of TxB(2) and PGE(2) concentrations prior to and
      up to 96 h postflunixin administration. Mean systemic clearance, steady-state
      volume of distribution and terminal elimination half-life was 0.767 +/- 0.098
      mL/min/kg, 0.137 +/- 0.12 L/kg, and 4.8 +/- 1.59 h, respectively. Four of the 16
      horses had serum concentrations in excess of the current ARCI recommended
      regulatory threshold at 24 h postadministration. TxB(2) suppression was
      significant for up to 24 h postadministration.

PMID- 25582762
TI  - Diagnostic power of fecal calprotectin in inflammatory and functional intestinal
      disorders.

PMID- 25582758
TI  - Adjuvants and lymphoma risk as part of the ASIA spectrum.
AB  - The emerging epidemic of Hodgkin and non-Hodgkin lymphomas worldwide continues to
      defy our understanding and forces the search for the causative factors. Adjuvants
      are known to act as triggers of immune and inflammatory responses. Animal
      experiments have demonstrated that long-term inflammation is related to
      aggravation of the immune network resulting in cellular and humoral responses
      leading to autoimmunity and lymphoma development. Chronic stimulation of the
      immune system is thought to be the key mechanism through which infectious
      diseases as well as autoimmune diseases can lead to lymphomagenesis. Many
      adjuvants can act similarly perturbing immune system's function, inducing a state
      of prolonged immune activation related to chronic lymphatic drainage. Several
      mechanisms were proposed by which adjuvants induce inflammation, and they are
      discussed herein. Some of them are triggering inflammasome; others bind DNA,
      lipid moieties in cells, induce uric acid production or act as lipophilic and/or
      hydrophobic substances. The sustained inflammation increases the risk of genetic
      aberrations, where the initial polyclonal activation ends in monoclonality. The
      latter is the hallmark of malignant lymphoma. Thus, chronic adjuvant stimulation
      may lead to lymphoma. 

PMID- 25582763
TI  - Barriers to referral for elevated blood pressure in the emergency department and
      differences between provider type.
AB  - A multidisciplinary sample of emergency department providers across the United
      States (n=450) were surveyed to identify barriers to referral for elevated blood
      pressure (BP) in the emergency department and differences between provider type.
      Registered nurses reported less knowledge of stage I hypertension (P=.043) and
      prehypertension (P<.01); were less aware of definitions for hypertension
      (P<.001); reported more difficulty in caring for patients who are asymptomatic
      (P=.007); required financial compensation to refer (P=.048); and perceived that
      BP referrals are influenced by the medical director (P<.001). Medical doctors
      reported more skills to refer (P=.008) and time as a barrier (P=.038). Physician
      assistants were more likely to report patients are not aware of health benefits
      (P=.035), doubted their concern for their BP (P=.023), and felt emotionally
      uncomfortable when referring (P=.025). Despite these differences, there was no
      significant difference between provider type and referral rates. 

PMID- 25582764
TI  - An efficient method for the purification of proteins from four distinct toxin
      antitoxin modules.
AB  - Toxin-antitoxin (TA) modules are stress response elements that are ubiquitous in
      the genomes of bacteria and archaea. Production and subsequent purification of
      individual TA proteins is anything but straightforward as over-expression of the
      toxin gene is lethal to bacterial and eukaryotic cells and over-production of the
      antitoxin leads to its proteolytic degradation because of its inherently
      unstructured nature. Here we describe an effective production and purification
      strategy centered on an on-column denaturant-induced dissociation of the toxin
      antitoxin complex. The success of the method is demonstrated by its application
      on four different TA families, encoding proteins with distinct activities and
      folds. A series of biophysical and in vitro activity tests show that the purified
      proteins are of high quality and suitable for structural studies. 

PMID- 25582765
TI  - Expression and purification of the N-terminal regulatory domain of Protein Kinase
      C for biophysical studies.
AB  - We report the protocol for heterologous expression and purification of the N
      terminal regulatory region of two Protein Kinase C (PKC)(1) isozymes, one
      conventional and one novel. Previous studies of these domains relied almost
      exclusively on the fusion constructs with high-molecular-weight solubility fusion
      partners such as GST and MBP. We developed experimental procedures that enabled
      us to overcome challenges associated with the amphiphilic character of the
      regulatory domain and generate sufficient quantities of fusion partner-free
      proteins for biophysical work. The key features of the protocol are the identity
      of the cleavable fusion partner, expression conditions, growth medium additives,
      introduction of mutation/solubility tags, and incorporation of osmolytes. The
      protein yields are sufficient for cost-effective production of isotopically
      enriched proteins for NMR work and biophysical studies in general. Our work opens
      up an avenue for the structural studies of these challenging proteins with high
      amphiphilic character. 

PMID- 25582766
TI  - Lactobacillus plantarum: microfiltration experiments for the production of
      probiotic biomass to be used in food and nutraceutical preparations.
AB  - Several studies have focused their attention on increasing the production of
      lactobacillus ssp. (LAB) biomass via-fermentation, in particular exploiting novel
      in situ product removal bioreactors that prevent accumulation of lactic acid, and
      therefore growth inhibition. Lactobacillus plantarum is one of the most studied
      species, used in nutritional supplements and in food processing. This research
      aimed to obtain high cell densities of L. plantarum, through fed-batch and
      microfiltration experiments. The latter achieved a 5-fold higher biomass density
      compared with batch experiments. Furthermore, the L. plantarum strain, isolated
      from Portoguese chorizo, was characterized for its ability to survive simulated
      digestion in vitro and competition potential toward certain common pathogens.
      Finally, the possibility of exploiting dairy liquid wastes (whey) as medium
      components was also explored demonstrating the strain's capability of
      metabolizing bovine-ovine whey. This finding might be relevant in liquid waste
      treatments of diary industries that are well distributed in our region.

PMID- 25582767
TI  - Outcomes of cervical end-to-side triangulating esophagogastric anastomosis with
      minimally invasive esophagectomy.
AB  - BACKGROUND: Esophagogastric anastomosis after esophagectomy has been performed
      with a variety of techniques during the past decade. However, anastomotic leakage
      and stricture are still important clinical problems after esophagogastric
      anastomosis, causing burdensome symptoms and poor quality of life. Herein, we
      describe a novel cervical end-to-side triangulating esophagogastric anastomoasis
      using linear stapler. METHODS: A total of 90 patients (85 % male; mean age 63
      years) with thoracic esophageal cancer who underwent cervical end-to-side
      esophagogastric triangular anastomosis using a linear stapler after minimally
      invasive esophagectomy between November 2006 and April 2013 were retrospectively
      reviewed. RESULTS: The median operation time was 602 min (range 424-936 min). The
      volume of blood loss during the entire operative procedure was 127 ml (range 0
      700 ml). There were no cases of anastomotic leakage in this study, although four
      patients (4.4 %) developed dysphagia associated with benign anastomotic stricture
      formation. All patients with a benign anastomotic stricture underwent balloon
      dilation, which resulted in improvement in their symptoms. CONCLUSIONS:
      Considering the absence of anastomotic leakage and low rate of anastomotic
      stricture formation in this study, our modified triangular esophagogastric
      anastomosis technique appears promising and may contribute to reduced morbidity
      and mortality rates following esophagectomy.

PMID- 25582769
TI  - Radiation tolerance of nanocrystalline ceramics: insights from Yttria Stabilized
      Zirconia.
AB  - Materials for applications in hostile environments, such as nuclear reactors or
      radioactive waste immobilization, require extremely high resistance to radiation
      damage, such as resistance to amorphization or volume swelling. Nanocrystalline
      materials have been reported to present exceptionally high radiation-tolerance to
      amorphization. In principle, grain boundaries that are prevalent in nanomaterials
      could act as sinks for point-defects, enhancing defect recombination. In this
      paper we present evidence for this mechanism in nanograined Yttria Stabilized
      Zirconia (YSZ), associated with the observation that the concentration of defects
      after irradiation using heavy ions (Kr(+), 400 keV) is inversely proportional to
      the grain size. HAADF images suggest the short migration distances in nanograined
      YSZ allow radiation induced interstitials to reach the grain boundaries on the
      irradiation time scale, leaving behind only vacancy clusters distributed within
      the grain. Because of the relatively low temperature of the irradiations and the
      fact that interstitials diffuse thermally more slowly than vacancies, this result
      indicates that the interstitials must reach the boundaries directly in the
      collision cascade, consistent with previous simulation results. Concomitant
      radiation-induced grain growth was observed which, as a consequence of the non
      uniform implantation, caused cracking of the nano-samples induced by local
      stresses at the irradiated/non-irradiated interfaces. 

PMID- 25582768
TI  - Long-term outcomes after total pancreatectomy: special reference to survivors'
      living conditions and quality of life.
AB  - BACKGROUND: Although recent studies have confirmed the safety of total
      pancreatectomy (TP), appropriate selection of patients for TP has not been well
      documented. Because patients require lifelong medical treatment and self
      management of pancreatic insufficiency after TP, indications for TP should be
      determined carefully according not only to disease factors but also to the social
      background of patients. We aimed to clarify long-term outcomes after TP,
      including the living conditions and quality of life (QoL), of surviving patients.
      METHODS: Medical records of 44 consecutive patients who underwent TP between 1990
      and 2013 were reviewed retrospectively; 25 survivors completed cross-sectional
      clinical surveys and responded to a questionnaire about QoL using Short Form
      36v2. RESULTS: Prevalence of morbidity and mortality after TP was 32 and 5 %,
      respectively. Postoperative complications occurred more frequently in elderly
      patients than in young patients (48 vs. 14 %; P = 0.02); however, there was no
      significant difference in mortality, postoperative hospital stay, or survival.
      Twenty-four of 25 survivors (96 %) could manage pancreatogenic diabetes by
      themselves, and the median level of glycosylated hemoglobin was 7.4 %. Although
      one-third of patients after TP complained of diarrhea and the QoL scores of
      patients with diarrhea were lower than those of patients without diarrhea, QoL
      scores after TP were virtually comparable with those of the national population,
      even in elderly patients. CONCLUSIONS: TP can be performed safely, even in
      elderly patients. QoL after TP seems to be acceptable if patients are capable of
      self-management.

PMID- 25582770
TI  - Has psychiatry tamed the "ketamine tiger?" Considerations on its use for
      depression and anxiety.
AB  - Ketamine has been available for approximately 50 years as an anesthetic agent. It
      is known to have potent effects on the central nervous system glutamatergic
      system, in particular blockade of N-methyl-D-aspartate (NMDA) receptors. Based
      upon pre-clinical evidence of involvement of the glutamatergic system in mood
      disorders, studies have been undertaken to test the antidepressant properties of
      ketamine. Several well-controlled studies, along with open-label case series,
      have established that ketamine can have rapid antidepressant effects.
      Additionally, data exist showing benefits of ketamine in post-traumatic stress
      disorder as well as obsessive compulsive disorder. However, improvements in these
      conditions tend to be short-lived with single infusions of ketamine. Of concern,
      ketamine has been associated with neurotoxicity in pre-clinical rodent models and
      is well-known to cause psychotomimetic effects and addiction in humans. While
      ketamine has been proven safe for use in sub-anesthetic doses administered once
      or a few times, the safety profile of prolonged use has not been established.
      Aspects of safety, possible mechanisms of action, and future directions of
      ketamine research are discussed in addition to the clinical literature on its use
      in psychiatric conditions.

PMID- 25582771
TI  - Extraction of DNA by magnetic ionic liquids: tunable solvents for rapid and
      selective DNA analysis.
AB  - DNA extraction represents a significant bottleneck in nucleic acid analysis. In
      this study, hydrophobic magnetic ionic liquids (MILs) were synthesized and
      employed as solvents for the rapid and efficient extraction of DNA from aqueous
      solution. The DNA-enriched microdroplets were manipulated by application of a
      magnetic field. The three MILs examined in this study exhibited unique DNA
      extraction capabilities when applied toward a variety of DNA samples and
      matrices. High extraction efficiencies were obtained for smaller single-stranded
      and double-stranded DNA using the benzyltrioctylammonium
      bromotrichloroferrate(III) ([(C8)3BnN(+)][FeCl3Br(-)]) MIL, while the dicationic
      1,12-di(3-hexadecylbenzimidazolium)dodecane bis[(trifluoromethyl)sulfonyl]imide
      bromotrichloroferrate(III) ([(C16BnIM)2C12(2+)][NTf2(-), FeCl3Br(-)]) MIL
      produced higher extraction efficiencies for larger DNA molecules. The MIL-based
      method was also employed for the extraction of DNA from a complex matrix
      containing albumin, revealing a competitive extraction behavior for the
      trihexyl(tetradecyl)phosphonium tetrachloroferrate(III) ([P6,6,6,14(+)][FeCl4(
      )]) MIL in contrast to the [(C8)3BnN(+)][FeCl3Br(-)] MIL, which resulted in
      significantly less coextraction of albumin. The MIL-DNA method was employed for
      the extraction of plasmid DNA from bacterial cell lysate. DNA of sufficient
      quality and quantity for polymerase chain reaction (PCR) amplification was
      recovered from the MIL extraction phase, demonstrating the feasibility of MIL
      based DNA sample preparation prior to downstream analysis. 

PMID- 25582772
TI  - Structural and biochemical characterization of MCAT from photosynthetic
      microorganism Synechocystis sp. PCC 6803 reveal its stepwise catalytic mechanism.
AB  - Malonyl-coenzyme A: acyl-carrier protein transacylase (MCAT) catalyzes the
      transfer of malonyl group from malonyl-CoA to the holo-acyl carrier protein (Holo
      ACP), yielding malonyl-ACP. The overall reaction has been extensively studied in
      heterotrophic microorganisms, while its mechanism in photosynthetic autotrophs as
      well as the stepwise reaction information remains unclear. Here the 2.42 A
      crystal structure of MCAT from photosynthetic microorganism Synechocystis sp. PCC
      6803 is presented. It demonstrates that Arg113, Ser88 and His188 constitute
      catalytic triad. The second step involved ACP-MCAT-malonyl intermediate is speed
      limited instead of the malonyl-CoA-MCAT intermediate in the first step. Therefore
      His87, Arg113 and Ser88 render different contributions for the two intermediates.
      Additionally, S88T mutant initializes the reaction by H87 deprotonating S88T
      which is different from the wild type.

PMID- 25582773
TI  - Lactic acid delays the inflammatory response of human monocytes.
AB  - Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or
      tumors, and influences local immune cell functions. We previously noted
      inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated
      monocytes. Here, we globally analyze the influence of LA on gene expression
      during monocyte activation. To separate LA-specific from lactate- or pH-effects,
      monocytes were treated for one or four hours with LPS in the presence of
      physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses
      of global gene expression profiles revealed striking effects of LA during the
      early stimulation phase. Up-regulation of most LPS-induced genes was
      significantly delayed in the presence of LA, while this inhibitory effect was
      attenuated in acidified samples and not detected after incubation with NaL. LA
      targets included genes encoding for important monocyte effector proteins like
      cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects
      were validated for several targets by quantitative RT-PCR and/or ELISA. Further
      analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation
      of protein kinase B (AKT) as well as the degradation of IkappaBalpha.
      Consistently, the LPS-induced nuclear accumulation of NFkappaB was also
      diminished in response to LA. These results indicate that the broad effect of LA
      on gene expression and function of human monocytes is at least partially caused
      by its interference with immediate signal transduction events after activation.
      This mechanism might contribute to monocyte suppression in the tumor environment.

PMID- 25582775
TI  - MILI, a PIWI family protein, inhibits melanoma cell migration through methylation
      of LINE1.
AB  - MILI, a member of the PIWI/AGO gene family, has been well documented to maintain
      genome integrity by transposon silencing in animal germ cells. It has been
      reported to be selectively expressed in precancerous stem cells (pCSCs), tumor
      cell lines and various malignancies. However, the underlying mechanism remains
      largely unclear. Here, we found that MILI is expressed in the melanoma cell line
      B16 but not in the highly metastatic mouse melanoma model B16BL6. Interestingly,
      the knockdown of MILI in B16 could activate MAGEA expression and increase the
      cell migration ability, whereas the overexpression of MILI in B16BL6 could
      inhibit MAGEA expression and decrease the cell migration ability. Further
      investigations showed that MILI can methylate LINE1, which is crucial for MAGEA
      expression and melanoma cell migration. Our results provide a novel function of
      MILI in melanoma metastasis and tumor progression.

PMID- 25582774
TI  - Differential effects of estrogen-dependent transactivation vs. transrepression by
      the estrogen receptor on invasiveness of HER2 overexpressing breast cancer cells.
AB  - Estrogen (E2) supports breast cancer cell growth but suppresses invasiveness and
      both actions are antagonized by anti-estrogens. As a consequence, anti-estrogen
      treatment may increase the invasive potential of estrogen receptor (ER)+ tumor
      cell sub-populations that are endocrine resistant due to HER2 amplification.
      Either transactivation or transrepression by E2/ER could lead to both up- and
      down-regulation of many genes. Inhibition of the transactivation function of ER
      is adequate to inhibit E2-dependent growth. However, the impact of inhibiting E2
      dependent transactivation vs. transrepression by ER on regulation of invasiveness
      by E2 is less clear. Here we dissect the roles of ER-mediated transactivation and
      transrepression in the regulation of invasiveness of ER+/HER2+ breast cancer
      cells by E2. Knocking down the general ER co-activators CBP and p300 prevented
      activation by E2 of its classical target genes but did not interfere with the
      ability of E2 to repress its direct target genes known to support invasiveness
      and tumor progression; there was also no effect on invasiveness or the ability of
      E2 to regulate invasiveness. On the other hand, overexpression of a co-repressor
      binding site mutant of ER (L372R) prevented E2-dependent transrepression but not
      transactivation. The mutant ER abrogated the ability of E2 to suppress
      invasiveness. E2 can partially down-regulate HER2 but knocking down HER2 below E2
      regulated levels did not affect invasiveness or the ability of E2 to regulate
      invasiveness, although it did inhibit growth. Therefore, in ER+/HER2+ cells, the
      E2-dependent transrepression by ER rather than its transactivation function is
      critical for regulation of invasiveness and this is independent of HER2
      regulation by E2. The findings suggest that selective inhibitors of
      transactivation by ER may be more beneficial in reducing tumor progression than
      conventional anti-estrogens that also antagonize E2-dependent transrepression. 

PMID- 25582776
TI  - Multiple lysines combined in HIV-1 Vif determines the responsiveness to CBF-beta.
AB  - The Vif (viral infectivity factor) protein of human immunodeficiency virus type-1
      (HIV-1) is critical for HIV-1 infectivity. CBF-beta is required for HIV-1 Vif
      function, as it increases the steady-state level of the HIV-1 Vif protein to
      promote host restriction factor APOBEC3 degradation. However, the precise
      mechanism by which CBF-beta promotes HIV-1 Vif levels remains unclear. In the
      present study, we provided evidences that CBF-beta promoted steady-state levels
      of HIV-1 Vif by inhibiting the degradation of HIV-1 Vif through the proteasome
      pathway. Our results reveal a new mechanism by which a cellular protein supports
      viral infectivity by inhibiting viral protein degradation. 

PMID- 25582777
TI  - AMP-activated protein kinase-dependent autophagy mediated the protective effect
      of sonic hedgehog pathway on oxygen glucose deprivation-induced injury of
      cardiomyocytes.
AB  - Sonic hedgehog (Shh) pathway has been reported to protect cardiomyocytes in
      myocardial infarction (MI), but the underlying mechanism is not clear. Here, we
      provide evidence that Shh pathway induces cardiomyocytes survival through AMP
      activated protein kinase-dependent autophagy. Shh pathway agonist SAG increased
      the expression of LC3-II, and induced the formation of autophagosomes in cultured
      H9c2 cardiomyocytes under oxygen glucose deprivation (OGD) 1 h and 4 h. Moreover,
      SAG induced a profound AMP-activated protein kinase (AMPK) activation, and then
      directly phosphorylated and activated the downstream autophagy initiator Ulk1,
      independent of the autophagy suppressor mammalian target of rapamycin (mTOR)
      complex 1. Taken together, our results have shown that Shh activates AMPK
      dependent autophagy in cardiomyocytes under OGD, suggesting a role of autophagy
      in Shh-induced cellular protection.

PMID- 25582779
TI  - Father Knows Best: Paternal Presence and Sexual Debut in African-American
      Adolescents Living in Poverty.
AB  - Adolescents found within single-parent families without a residential father have
      reported higher levels of sexual debut and higher levels of reported pregnancy.
      Using data from the Mobile Youth Survey, the purpose of this study is to
      determine the impact of the presence of a father figure on the sexual debut of
      African-American adolescents living in poverty and to determine if gender
      moderates the relationship between the presence of a father figure and sexual
      debut. Additionally, this study will examine the family processes in which the
      presence of a father figure can affect the sexual debut of African-American
      adolescents who live within economically and socially disadvantaged communities.
      The results revealed that African-American adolescents reporting a father figure
      had lower rates of sexual debut than those youth reporting no father figure.
      Gender was not found to be a significant moderator in the relationship between
      father figure presence and sexual debut. However, existing curfews and family
      rules did account for some of the effects of presence of a father figure and
      sexual debut. The results suggest that when adolescents have a father figure in
      their lives, it may reduce the possibility of early sexual debut. 

PMID- 25582778
TI  - EGFR mediates astragaloside IV-induced Nrf2 activation to protect cortical
      neurons against in vitro ischemia/reperfusion damages.
AB  - In this study, we tested the potential role of astragaloside IV (AS-IV) against
      oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damages in murine
      cortical neurons, and studied the associated signaling mechanisms. AS-IV exerted
      significant neuroprotective effects against OGD/R by reducing reactive oxygen
      species (ROS) accumulation, thereby attenuating oxidative stress and neuronal
      cell death. We found that AS-IV treatment in cortical neurons resulted in NF-E2
      related factor 2 (Nrf2) signaling activation, evidenced by Nrf2 Ser-40
      phosphorylation, and its nuclear localization, as well as transcription of
      antioxidant-responsive element (ARE)-regulated genes: heme oxygenase-1 (HO-1),
      NAD(P)H:quinone oxidoreductase 1 (NQO-1) and sulphiredoxin 1 (SRXN-1). Knockdown
      of Nrf2 through lentiviral shRNAs prevented AS-IV-induced ARE genes
      transcription, and abolished its anti-oxidant and neuroprotective activities.
      Further, we discovered that AS-IV stimulated heparin-binding-epidermal growth
      factor (HB-EGF) release to trans-activate epidermal growth factor receptor (EGFR)
      in cortical neurons. Blockage or silencing EGFR prevented Nrf2 activation by AS
      IV, thus inhibiting AS-IV-mediated anti-oxidant and neuroprotective activities
      against OGD/R. In summary, AS-IV protects cortical neurons against OGD/R damages
      through activating of EGFR-Nrf2 signaling. 

PMID- 25582780
TI  - Visualization of structural organization of ventral membranes of sheared-open
      resorbing osteoclasts attached to apatite pellets.
AB  - Osteoclasts are highly polarized cells from both morphological and functional
      points of view. Using quick-freeze, rotary-replication methods combined with cell
      shearing, we clarified the variability of cytoplasmic surface of the polarized
      membranes of osteoclasts seeded on apatite. As to the organization of actin
      filaments and clathrin sheets, we confirmed almost the same ventral membrane
      specializations of osteoclasts on apatite as seen on glass plates. The organized
      actin filaments and membrane-associated particles supported the ruffled border
      membranes. Inside the actin sealing zone, membrane specializations were not
      always occupied with the ruffled border but also with other types of membranes.
      Some osteoclasts formed an actin ring but lacked the ruffled border projections.
      We report a unique and distinctive membrane modification of apatite-attached
      osteoclasts, i.e., the presence of dense aggregates of membrane-associated
      particles and related structures not found in the osteoclasts seeded on glass
      plates. Actin filament polarity in the podosomes was determined by decoration
      with myosin S1. The actin filament polarity within podosome appears to be
      oriented predominantly with its barbed ends toward the core, whereas the
      interconnecting F-actin appears to be mixed oriented. Two different types of
      clathrin plaques displayed different distributions: clathrin-dependent
      endocytosis was observed in the ruffled border regions, whereas flat clathrin
      sheets were found in the leading edge of lamellipodia and near podosomes. The
      clathrin sheets adhered to the apatite surface tightly on the ventral membranes
      overlaying the resorption lacunae. All these membrane specializations as
      mentioned above may indicate the functional variability of osteoclasts seeded on
      apatite. 

PMID- 25582781
TI  - Behavioural and eye-movement outcomes in response to text-based reading treatment
      for acquired alexia.
AB  - Text-based reading treatments, such as Multiple Oral Rereading (MOR) and Oral
      Reading for Language in Aphasia (ORLA) have been used successfully to remediate
      reading impairments in individuals with acquired alexia, but the mechanisms
      underlying such improvements are not well understood. In this study, an
      individual with acquired alexia who demonstrated reliance on a sub-lexical
      reading strategy (i.e., presence of spelling regularity effect and phonologically
      plausible errors) underwent 12 weeks of text-based reading treatment combining
      MOR and ORLA procedures. Behavioural assessments of single-word and text reading,
      along with eye-tracking assessments were conducted pre-treatment, post-treatment
      and at 5 month follow-up. Improved reading fluency (rate, accuracy) was observed
      for both trained and untrained passages. Evidence from behavioural and eye
      tracking assessment suggested text-based reading treatment facilitated use of a
      lexical-semantic reading strategy. Increased frequency and lexicality effects, as
      well as a shift in initial landing position towards the centre of the word (the
      "optimal viewing position") were observed at post-treatment and follow-up
      assessments. These results demonstrate the potential utility of using eye
      movements as a parameter of interest in addition to traditional behavioural
      outcomes when investigating response to reading treatment.

PMID- 25582782
TI  - Assessing soil and groundwater contamination from biofuel spills.
AB  - Future modifications of fuels should include evaluation of the proposed
      constituents for their potential to damage environmental resources such as the
      subsurface environment. Batch and column experiments were designed to simulate
      biofuel spills in the subsurface environment and to evaluate the sorption and
      desorption behavior of target fuel constituents (i.e., monoaromatic and
      polyaromatic hydrocarbons) in soil. The extent and reversibility of the sorption
      of aromatic biofuel constituents onto soil were determined. When the ethanol
      content in ethanol-blended gasoline exceeded 25%, enhanced desorption of the
      aromatic constituents to water was observed. However, when biodiesel was added to
      diesel fuel, the sorption of target compounds was not affected. In addition, when
      the organic carbon content of the soil was higher, the desorption of target
      compounds into water was lower. The empirical relationships between the organic
      carbon normalized sorption coefficient (Koc) and water solubility and between Koc
      and the octanol-water partition coefficient (Kow) were established. Column
      experiments were carried out for the comparison of column effluent
      concentration/mass from biofuel-contaminated soil. The dissolution of target
      components depended on chemical properties such as the hydrophobicity and total
      mass of biofuel. This study provides a basis for predicting the fate and
      transport of hydrophobic organic compounds in the event of a biofuel spill. The
      spill scenarios generated can assist in the assessment of biofuel-contaminated
      sites. 

PMID- 25582783
TI  - Characteristics that Predict Ophthalmic Knowledge among Ophthalmology Residents.

PMID- 25582784
TI  - The early treatment in diabetic retinopathy study chart compared with the
      tumbling-E and Landolt-C.

PMID- 25582785
TI  - Local anesthetic agents for vitreoretinal surgery: no advantage to mixing
      solutions.
AB  - PURPOSE: To compare the efficacy of lidocaine, bupivacaine, and a mixture of both
      in patients undergoing peribulbar anesthesia for vitreoretinal surgery. DESIGN:
      Cross-sectional study. PARTICIPANTS: Ninety patients. METHODS: Patients who
      underwent vitreoretinal surgery were randomized into 3 groups based on the
      peribulbar injection they received: lidocaine, bupivacaine, or a combination of
      lidocaine and bupivacaine. MAIN OUTCOME MEASURES: Time of onset of analgesia,
      akinesia, and intraoperative pain, if any, was noted. The efficacy of the block
      was graded from 0 to 5 depending on the adequacy of anesthesia and akinesia and
      the need for local supplementation. RESULTS: Mean times of onset (+/- standard
      deviation) of sensory blockade for the lidocaine, bupivacaine, and combination
      groups were 2.14+/-0.18, 2.19+/-0.13, and 2.17+/-0.11 minutes, respectively (P =
      0.103). Mean times of onset (+/- standard deviation) of motor blockade for the
      lidocaine, bupivacaine, and combination groups were 3.04+/-1.81, 4.04+/-2.68, and
      3.38+/-2.48 minutes, respectively (P = 0.255). Mean time of onset of
      intraoperative pain for the bupivacaine group, 149.33+/-46.33 minutes, was
      prolonged significantly compared with that of the combination group, 115.83+/
      34.49 minutes, and that of the lidocaine group, 94.17+/-49.86 minutes (P <
      0.001). Adequate anesthesia and akinesia (grade 5) were achieved in 56.7% of the
      patients in the bupivacaine group compared with 23.3% in the lidocaine group and
      30% in the combination group (P = 0.049). CONCLUSIONS: In peribulbar anesthesia,
      0.5% bupivacaine solution provides better quality of anesthesia than does
      combination 2% lidocaine and 0.5% bupivacaine in patients undergoing
      vitreoretinal surgery.

PMID- 25582787
TI  - Submyeloablative conditioning with busulfan permits bone marrow-derived cell
      accumulation in a murine model of Alzheimer's disease.
AB  - Previous work has suggested that bone marrow (BM)-derived cells (BMDCs)
      accumulate within the CNS and could potentially associate with beta-amyloid
      plaques in Alzheimer's disease (AD). To explore the accumulation of BMDCs in
      murine AD, we transplanted green fluorescent protein (GFP)-labeled BM cells into
      triple transgenic (3*Tg) and wild-type (wt) mice using non-irradiative
      myelosuppresive conditioning with busulfan (BU). We find that BU (80mg/kg) is
      sufficient to obtain adequate chimerism (>85%) in wt mice. In order to obtain
      appreciable non-irradiative chimerism in the 3*Tg mice (>80%), anti-asialo
      ganglio-N-tetraosylceramide (alpha-ASGM-1) antibody was also used to reduce
      natural killer cell function and thereby abrogate the hybrid resistance of the
      3*Tg mouse strain. Using BU conditioning and alpha-ASGM-1 together, we observed
      sustained BM chimerism and BMDC accumulation within the CNS of the 3*Tg and wt
      mice. In cortex and hippocampus, BMDC accumulation was perivascular in
      distribution and similar between 3*Tg and wt mice, with no clear association
      between BMDCs and AD plaques. We conclude that non-irradiative BM chimerism can
      be achieved with BU in 3*Tg mice, but requires alpha-ASGM-1 (or similar
      appropriate NK-cell depletion). Use of this chimerism protocol permits BMDCs
      accumulation in the CNS of mixed strain recipient mice although BMDCs appear to
      be largely perivascular within cortex and hippocampus. 

PMID- 25582789
TI  - A year in review in Minerva Anestesiologica 2014. Critical care. Experimental and
      clinical studies.

PMID- 25582790
TI  - Correction.
AB  - [This corrects the article DOI: 10.1136/bmjresp-2013-000010.]. 

PMID- 25582788
TI  - Preliminary findings suggest the number and volume of supragranular and
      infragranular pyramidal neurons are similar in the anterior superior temporal
      area of control subjects and subjects with autism.
AB  - We investigated the cytoarchitecture of the anterior superior temporal area (TA2)
      of the postmortem cerebral cortex in 9 subjects with autism and 9 age-matched
      typically developing subjects between the ages of 13 and 56 years. The superior
      temporal gyrus is involved in auditory processing and social cognition and its
      pathology has been correlated with autism. We quantified the number and soma
      volume of pyramidal neurons in the supragranular layers and pyramidal neurons in
      the infragranular layers in each subject. We did not find significant differences
      in the number or volume of supragranular or infragranular neurons in the cerebral
      cortex of subjects with autism compared to typically developing subjects. This
      report does not support an alteration of supragranular to infragranular neurons
      in autism. However, further stereological analysis of the number of cells and
      cell volumes in specific cortical areas is needed to better establish the
      cellular phenotype of the autistic cerebral cortex and to understand its clinical
      relevance in autism. 

PMID- 25582786
TI  - Spine synapse remodeling in the pathophysiology and treatment of depression.
AB  - Clinical brain imaging and postmortem studies provide evidence of structural and
      functional abnormalities of key limbic and cortical structures in depressed
      patients, suggesting that spine synapse connectivity is altered in depression.
      Characterization of the cellular determinants underlying these changes in
      patients are limited, but studies in rodent models demonstrate alterations of
      dendrite complexity and spine density and function that could contribute to the
      morphological and functional alterations observed in humans. Rodent studies
      demonstrate region specific effects in chronic stress models of depression,
      including reductions in dendrite complexity and spine density in the hippocampus
      and prefrontal cortex (PFC) but increases in the basolateral amygdala and nucleus
      accumbens. Alterations of spine synapse connectivity in these regions are thought
      to contribute to the behavioral symptoms of depression, including disruption of
      cognition, mood, emotion, motivation, and reward. Studies of the mechanisms
      underlying these effects demonstrate a role for altered brain derived
      neurotrophic factor (BDNF) signaling that regulates synaptic protein synthesis.
      In contrast, there is evidence that chronic antidepressant treatment can block or
      reverse the spine synapse alterations caused by stress. Notably, the new fast
      acting antidepressant ketamine, which produces rapid therapeutic actions in
      treatment resistant MDD patients, rapidly increases spine synapse number in the
      PFC of rodents and reverses the effects of chronic stress. The rapid synaptic and
      behavioral actions of ketamine occur via increased BDNF regulation of synaptic
      protein synthesis. Together these studies provide evidence for a neurotophic and
      synaptogenic hypothesis of depression and treatment response and indicate that
      spine synapse connectivity in key cortical and limbic brain regions is critical
      for control of mood and emotion. 

PMID- 25582791
TI  - Corneal confocal microscopy detects small fiber damage in chronic inflammatory
      demyelinating polyneuropathy (CIDP).
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune
      mediated peripheral neuropathy with multifocal involvement. Reliable biomarkers
      for diagnosis, disease progression, and treatment response remain to be
      developed. We assessed the utility of corneal confocal microscopy (CCM) as a
      diagnostic marker for CIDP in 16 patients. CCM parameters including corneal nerve
      fiber density (NFD), nerve fiber length, number of main nerve trunks, number of
      nerve branches, nerve tortuosity, and dendritic cell density (DCD) were compared
      to those from 15 healthy controls and correlated with clinical and
      electrophysiological findings. CIDP patients had a significantly lower corneal
      NFD compared to healthy controls. The total nerve fiber length and the number of
      nerve branches were significantly decreased, whereas nerve tortuosity was
      increased in patients with CIDP. There was no positive correlation between
      corneal NFD and clinical or electrophysiological assessments. The average DCD was
      not significantly different in CIDP patients and controls. CCM measures suggest
      damage to small sensory afferents in the cornea in CIDP patients. Further studies
      are needed to compare different neuropathic conditions and to explore
      longitudinal changes of CCM parameters. 

PMID- 25582792
TI  - Lack of pulse and surge modes and glutamatergic stimulation of luteinising
      hormone release in Kiss1 knockout rats.
AB  - Kisspeptin, encoded by the Kiss1 gene, has attracted attention as a key candidate
      neuropeptide in controlling puberty and reproduction via regulation of
      gonadotrophin-releasing hormone (GnRH) secretion in mammals. Pioneer studies with
      Kiss1 or its cognate receptor Gpr54 knockout (KO) mice showed the indispensable
      role of kisspeptin-GPR54 signalling in the control of animal reproduction,
      although detailed analyses of gonadotrophin secretion, especially pulsatile and
      surge-mode of luteinising hormone (LH) secretion, were limited. Thus, in the
      present study, we have generated Kiss1 KO rats aiming to evaluate a key role of
      kisspeptin in governing reproduction via pulse and surge modes of GnRH/LH
      secretion. Kiss1 KO male and female rats showed a complete suppression of
      pulsatile LH secretion, which is responsible for folliculogenesis and
      spermatogenesis, and an absence of puberty and atrophic gonads. Kiss1 KO female
      rats showed no spontaneous LH/follicle-stimulating hormone surge and an oestrogen
      induced LH surge, suggesting that the GnRH surge generation system, which is
      responsible for ovulation, does not function without kisspeptin. Furthermore,
      challenge of major stimulatory neurotransmitters, such as monosodium glutamate,
      NMDA and norepinephrine, failed to stimulate LH secretion in Kiss1 KO rats,
      albeit they stimulated LH release in wild-type controls. Taken together, the
      results of the present study confirm that kisspeptin plays an indispensable role
      in generating two modes (pulse and surge) of GnRH/gonadotrophin secretion to
      regulate puberty onset and normal reproductive performance. In addition, the
      present study suggests that kisspeptin neurones play a critical role as a hub
      integrating major stimulatory neural inputs to GnRH neurones, using newly
      established Kiss1 KO rats, which serve as a useful model for detailed analysis of
      hormonal profiles. 

PMID- 25582794
TI  - Antimicrobial susceptibility testing for bovine respiratory disease: getting more
      from diagnostic results.
AB  - Bovine respiratory disease (BRD) is one of the most common diseases of cattle
      worldwide. Given the significant bacterial component of this disease,
      antimicrobial agents remain one of the mainstays of therapy. However, the
      potential welfare and economic impact resulting from the selection of
      inappropriate antimicrobial therapy for BRD poses significant risks to both
      animal and animal owner. To determine the 'best' antimicrobial agent for a
      specific case, the decision-making process needs to incorporate all available
      evidence, often including the results of bacterial culture and antimicrobial
      susceptibility testing. While antimicrobial susceptibility testing can be a
      valuable diagnostic tool, integrating the test results into the clinical decision
      making process can be a challenging experience. This review details the process
      by which interpretive criteria for susceptibility tests are developed. Principles
      for how to best integrate antimicrobial susceptibility testing, both at the
      individual animal test and aggregate test levels, into the clinical decision
      making process are discussed. Non-traditional testing methodologies and how they
      may improve susceptibility testing in the future are also reviewed. 

PMID- 25582793
TI  - Predictors and outcomes of Mycobacterium tuberculosis bacteremia among patients
      with HIV and tuberculosis co-infection enrolled in the ACTG A5221 STRIDE study.
AB  - BACKGROUND: We evaluated predictors and outcomes of Mycobacterium tuberculosis
      bacteremia among participants undergoing baseline mycobacterial blood culture in
      the ACTG A5221 STRIDE study, a randomized clinical trial comparing earlier with
      later ART among HIV-infected patients suspected of having tuberculosis with CD4
      positive T-lymphocyte counts (CD4 counts) <250 cells/mm(3). We conducted a
      secondary analysis comparing participants with respect to presence or absence of
      M. tuberculosis bacteremia. METHODS: Participants with a baseline mycobacterial
      blood culture were compared with respect to the presence or absence of M.
      tuberculosis bacteremia. Baseline predictors of M. tuberculosis bacteremia were
      identified and participant outcomes were compared by mycobacteremia status.
      RESULTS: Of 90 participants with baseline mycobacterial blood cultures, 29
      (32.2%) were female, the median (IQR) age was 37 (31-45) years, CD4 count was 81
      (33-131) cells/mm(3), HIV-1 RNA level was 5.39 (4.96-5.83) log10 copies/mL, and
      18 (20.0%) had blood cultures positive for M. tuberculosis. In multivariable
      analysis, lower CD4 count (OR 0.85 per 10-cell increase, p = 0.012), hemoglobin
      <=8.5 g/dL (OR 5.8, p = 0.049), and confirmed tuberculosis (OR 17.4, p = 0.001)
      were associated with M. tuberculosis bacteremia. There were no significant
      differences in survival and AIDS-free survival, occurrence of tuberculosis immune
      reconstitution inflammatory syndrome (IRIS), or treatment interruption or
      discontinuation by M. tuberculosis bacteremia status. IRIS did not differ
      significantly between groups despite trends toward more virologic suppression and
      greater CD4 count increases at week 48 in the bacteremic group. CONCLUSIONS:
      Among HIV-infected tuberculosis suspects, lower CD4 count, hemoglobin <=8.5 g/dL,
      and the presence of microbiologically confirmed pulmonary tuberculosis were
      associated with increased adjusted odds of mycobacteremia. No evidence of an
      association between M. tuberculosis bacteremia and the increased risk of IRIS was
      detected. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00108862 .

PMID- 25582795
TI  - A randomised controlled study to assess the effects of an extension programme on
      the 6 week in-calf rate of seasonal calving, pasture-based dairy herds in New
      Zealand.
AB  - The aim of this study was to quantify the effect of participation by New Zealand
      dairy farmers in a year-long extension programme designed to improve herd
      reproductive performance. This was estimated by comparing, over two successive
      years, the proportions of cows becoming pregnant during the first 6 weeks of the
      seasonal breeding programme (6 week in-calf rate) in herds involved in a full
      participation group (treatment), with herds in an actively monitored control
      group or a passively monitored control group. Possible interactions between
      treatment and various biophysical and socio-demographic factors were also
      assessed. Multivariable modelling was used to determine the effect of treatment
      on 6 week in-calf rate, adjusting for design factors (study year and region). It
      was estimated that the 6 week in-calf rate was 68% (95% confidence interval 65
      67%) in the treatment group of farms that participated in the extension programme
      compared with 66% (95% confidence interval 67-69%) in the actively monitored
      control group of farms that did not participate in the extension programme (P=
      0.05); thus the risk difference was 2.0% (95% confidence interval 0.0-3.9%). No
      significant interactions were found between treatment and region, study year or
      any of the biophysical and socio-demographic variables on the 6 week in-calf rate
      (P > 0.05). There was no significant difference in the 6 week in-calf rate
      between the actively and passively monitored control groups (P= 0.56). It was
      concluded that enrolment in the extension programme improved the 6 week in-calf
      rate, and that the treatment effect was not modified substantially by region,
      study year or any of the biophysical and socio-demographic variables assessed.

PMID- 25582796
TI  - Heart rate and salivary cortisol concentrations in foals at birth.
AB  - Heart rate (HR), HR variability (HRV) and salivary cortisol concentrations were
      determined in foals (n = 13) during the perinatal phase and until 5 months of
      age. In the fetus, HR decreased from 77 +/- 3 beats/min at 120 min before birth
      to 60 +/- 1 beats/min at 5 min before birth (P <0.01). Within 30 min of birth, HR
      increased to 160 +/- 9 beats/min (P <0.01). Salivary cortisol concentrations
      immediately after birth were 11.9 +/- 3.6 ng/mL and within 2 h increased to a
      maximum of 52.5 +/- 12.3 ng/mL (P <0.01). In conclusion, increases in HR and
      salivary cortisol concentrations in foals are not induced during parturition, but
      occur immediately after birth.

PMID- 25582797
TI  - A review of the pharmacology and clinical application of alfaxalone in cats.
AB  - Alfaxalone-2-hydroxpropyl-beta-cyclodextrin (alfaxalone-HPCD) was first marketed
      for veterinary use in Australia in 2001 and has since progressively became
      available throughout the world, including the USA, where in 2012 Food and Drug
      Administration (FDA) registration was granted. Despite the growing body of
      published works and increasing global availability of alfaxalone-HPCD, the
      accumulating evidence for its use in cats has not been thoroughly reviewed. The
      purpose of this review is: (1) to detail the pharmacokinetic properties of
      alfaxalone-HPCD in cats; (2) to assess the pharmacodynamic properties of
      alfaxalone-HPCD, including its cardiovascular, respiratory, central nervous
      system, neuromuscular, hepatic, renal, haematological, blood-biochemical,
      analgesic and endocrine effects; and (3) to consider the clinical application of
      alfaxalone-HPCD for sedation, induction and maintenance of anaesthesia in cats.
      Based on the published literature, alfaxalone-HPCD provides a good alternative to
      the existing intravenous anaesthetic options for healthy cats.

PMID- 25582798
TI  - Veterinary oncology clinical trials: design and implementation.
AB  - There has been a recent increase in interest among veterinarians and the larger
      biomedical community in the evaluation of novel cancer therapies in client-owned
      (pet) animals with spontaneous cancer. This includes novel drugs designed to be
      veterinary therapeutics, as well as agents for which data generated in animals
      with tumors may inform human clinical trial design and implementation. An
      understanding of the process involved in moving a therapeutic agent through the
      stages of clinical evaluation is critical to the successful implementation of
      clinical investigations, as well as interpretation of the veterinary oncology
      literature. This review outlines considerations in the design and conduct of the
      various phases of oncology clinical trials, along with recent
      adaptations/modifications of these basic designs that can enhance the generation
      of timely and meaningful clinical data. 

PMID- 25582799
TI  - Canine osteosarcoma: understanding its variability to improve treatment.

PMID- 25582800
TI  - Mindfulness-based cognitive therapy for youth with anxiety disorders at risk for
      bipolar disorder: a pilot trial.
AB  - AIM: Children and adolescents with bipolar parents have an elevated risk for
      anxiety disorders. However, antidepressant medications commonly used to treat
      symptoms of anxiety may accelerate the onset of mania in these already at-risk
      youth. Therefore, studies evaluating innovative non-pharmacologic treatments for
      anxiety in this population are urgently needed. METHODS: Subjects participated in
      12 weekly sessions of mindfulness-based cognitive therapy for children (MBCT-C),
      a manualized group psychotherapeutic intervention utilizing cognitive behavioural
      principles and mindfulness exercises to increase regulation of attention and non
      judgmental acceptance of present moment thoughts, emotions and experiences.
      Independent raters administered symptoms rating scales prior to each treatment
      session. Spearman correlations and paired-samples signed rank tests were used to
      examine outcomes. After-intervention surveys and session transcripts were
      reviewed to assess feasibility and acceptability of the intervention. RESULTS:
      Participants included 10 youth (meanage  = 13.2; 80% girls; 40% biracial) with
      generalized, social and/or separation anxiety disorders, and a parent with
      bipolar disorder. Clinician-rated anxiety was significantly reduced after
      intervention (meanbefore  = 11.1; meanafter  = 4.3; P < 0.01), as well as youth
      rated trait anxiety (P = 0.03). Parent-rated emotion regulation significantly
      increased from before to after intervention (P = 0.05). Increases in mindfulness
      were associated with decreases in anxiety (P = 0.03). Finally, children and
      parents/guardians reported high levels of feasibility, acceptability and
      usefulness of the intervention. CONCLUSION: Findings support the feasibility,
      acceptability and preliminary efficacy of MBCT-C for treating anxiety in youth at
      risk for bipolar disorder. Future controlled and larger studies are needed to
      confirm these preliminary findings.

PMID- 25582801
TI  - Changes in the association between health complaint frequency and medicine use
      among adolescents in Scotland between 1998 and 2010.
AB  - OBJECTIVE: Medicines have the potential to cause harm, particularly when
      adolescents do not follow recommendations for use. In addition, medicine use in
      adolescence has been shown to track into adulthood. There is therefore a strong
      rationale to monitor changes in adolescent medicine use over time and understand
      the mechanisms behind these changes METHODS: Data from the 1998, 2006 and 2010
      Scotland Health Behaviour in School-aged Children Survey were modelled using
      multilevel logistic regression, modelling medicine use for: headache,
      stomachache, sleeping difficulties and nervousness, as well as a combined
      medicine use measure. Models adjusted for year and frequency of health complaints
      to measure trends in medicine use, and an interaction term to measure the
      relationship between medicine use and health complaint frequency. RESULTS:
      Medicine use reduced between 1998 and 2010. Hownever having the majority of the
      reduction was observed between 1998 and 2006 for all five outcomes. Adjustment
      for health complaint frequency only explained some of this reduction. When an
      interaction term was added between year and health complaint frequency this was
      significant for boys' medicine use, suggesting that health complaint frequency
      became a better predictor of medicine use with time. Medicine use for stomachache
      among girls increased over time, and this increase became more pronounced after
      adjustment for stomachache frequency. CONCLUSION: Changes in health complaint
      frequency were only partly associated with reductions in medicine use between
      1998 and 2010. Further monitoring of medicine use is recommended, particularly
      the use of medicine for sleep difficulties, and for stomachache among girls.

PMID- 25582803
TI  - A confirmatory factor analytic validation of the Tinnitus Handicap Inventory.
AB  - OBJECTIVE: Because the postulated three-factor structure of the internationally
      widely used Tinnitus Handicap Inventory (THI) has not been confirmed yet by a
      confirmatory factor analytic approach this was the central aim of the current
      study. METHODS: From a clinical setting, N=373 patients with chronic tinnitus
      completed the THI and further questionnaires assessing tinnitus-related and
      psychological variables. In order to analyze the psychometric properties of the
      THI, confirmatory factor analysis (CFA) and correlational analyses were
      conducted. RESULTS: CFA provided a statistically significant support for a better
      fit of the data to the hypothesized three-factor structure (RMSEA=.049,
      WRMR=1.062, CFI=.965, TLI=.961) than to a general factor model (RMSEA=.062,
      WRMR=1.258, CFI=.942, TLI=.937). The calculation of Cronbach's alpha as indicator
      of internal consistency revealed satisfactory values (.80-.91) with the exception
      of the catastrophic subscale (.65). High positive correlations of the THI and its
      subscales with other measures of tinnitus distress, anxiety, and depression, high
      negative correlations with tinnitus acceptance, moderate positive correlations
      with anxiety sensitivity, sleeping difficulties, tinnitus loudness, and small
      correlations with the Big Five personality dimensions confirmed construct
      validity. CONCLUSION: Results show that the THI is a highly reliable and valid
      measure of tinnitus-related handicap. In contrast to results of previous
      exploratory analyses the current findings speak for a three-factor in contrast to
      a unifactorial structure. Future research is needed to replicate this result in
      different tinnitus populations.

PMID- 25582802
TI  - Family history of mental illness or alcohol abuse and the irritable bowel
      syndrome.
AB  - OBJECTIVE: We have observed that many patients with IBS drink very little alcohol
      and postulated that this may reflect membership in families affected by
      alcoholism and mental illness. We aimed to evaluate whether a family history of
      substance or alcohol abuse, or psychiatric illness, is associated with IBS.
      METHODS: A valid GI questionnaire was mailed to a randomly selected population
      based cohort to identify IBS and healthy controls. The electronic medical record
      was reviewed to record the subjects' self-reported personal and family health
      histories. RESULTS: A total of 2300 subjects responded (response rate 55%; IBS
      13%, n=287); 230 subjects with IBS and 318 controls were eligible. Family history
      of alcohol/substance abuse was reported by 33% of cases and 25% of controls
      (OR=1.4, 95% CI=1.0-2.1, p=0.06). Family history of psychiatric illness was
      reported by 37% of cases and 22% of controls (OR=2.0, 95% CI=1.3-2.9, p<0.001).
      In the absence of a personal history of alcohol use, a family history of
      alcohol/substance abuse was predictive of IBS status (OR adjusted for age and
      gender=1.5, 95% CI=1.0-2.3, p=0.05). In the absence of a personal history of
      alcohol use, reporting both a family history of alcohol/substance abuse and
      anxiety/depression/mental illness was clearly predictive of IBS status (OR=2.5,
      95% CI=1.4-4.5; p<0.005). Substance abuse as a child was associated with an
      increased risk of IBS (OR=2.3, 95% CI=1.1-4.8; p<0.03). CONCLUSION: IBS is
      independently associated with a family history of psychiatric illness and may be
      linked to a family history of alcohol/substance abuse.

PMID- 25582804
TI  - Effect of arm swing strategy on local dynamic stability of human gait.
AB  - INTRODUCTION: Falling causes long term disability and can even lead to death.
      Most falls occur during gait. Therefore improving gait stability might be
      beneficial for people at risk of falling. Recently arm swing has been shown to
      influence gait stability. However at present it remains unknown which mode of arm
      swing creates the most stable gait. AIM: To examine how different modes of arm
      swing affect gait stability. METHOD: Ten healthy young male subjects volunteered
      for this study. All subjects walked with four different arm swing instructions at
      seven different gait speeds. The Xsens motion capture suit was used to capture
      gait kinematics. Basic gait parameters, variability and stability measures were
      calculated. RESULTS: We found an increased stability in the medio-lateral
      direction with excessive arm swing in comparison to normal arm swing at all gait
      speeds. Moreover, excessive arm swing increased stability in the anterior
      posterior and vertical direction at low gait speeds. Ipsilateral and inphase arm
      swing did not differ compared to a normal arm swing. DISCUSSION: Excessive arm
      swing is a promising gait manipulation to improve local dynamic stability. For
      excessive arm swing in the ML direction there appears to be converging evidence.
      The effect of excessive arm swing on more clinically relevant groups like the
      more fall prone elderly or stroke survivors is worth further investigating.
      CONCLUSION: Excessive arm swing significantly increases local dynamic stability
      of human gait.

PMID- 25582806
TI  - Rationalization and Design of Enhanced Photoinduced Cycloreversion in
      Photochromic Dimethyldihydropyrenes by Theoretical Calculations.
AB  - This study presents a computational investigation of the initial step of the
      dimethyldihydropyrene (DHP) to cyclophanediene (CPD) photoinduced ring-opening
      reaction using time-dependent density functional theory (TD-DFT). In particular,
      the photochemical path corresponding to the formation of the CPD precursor (CPD*)
      on the zwitterionic state is scrutinized. The TD-DFT approach was first validated
      on the parent compound against accurate ab initio calculations. It confirms that
      CPD* formation is efficiently quenched in this system by an easily accessible
      S2/S1 conical intersection located in the vicinity of the CPD* minimum and
      leading to a locally excited state minimum responsible for DHP luminescence.
      Increased ring-opening quantum yields were observed in benzo[e]-fused-DHP (DHP
      1), isobutenyl-DHP (DHP-2), and naphthoyl-DHP (DHP-3). The calculations show that
      CPD* formation is much more favorable in these systems, either due to an
      inversion of electronic states in DHP-1, suppressing the formation of the locally
      excited state, or due to efficient stabilization of CPD* on the S1 potential
      energy surface in DHP-2 and DHP-3. Both effects can be combined in a rationally
      designed benzo[e]-fused-naphthoyl-DHP (DHP-4) for which we anticipate an
      unprecedented efficiency. 

PMID- 25582805
TI  - Energy flow analysis of the lower extremity during gait in persons with chronic
      stroke.
AB  - BACKGROUND: A decline in walking capacity and high energy cost can limit mobility
      following stroke. Mechanical energy exchange between lower limb and trunk
      segments can reflect gait inefficiencies, but reveals little about active energy
      flow between adjacent segments through muscle actions. This study evaluated
      mechanical energy expenditures (MEEs) during walking in stroke and healthy groups
      to understand movement control and explore the impact of walking speed on
      mechanical energy exchanges. METHODS: Thirteen adults with hemiparesis and six
      healthy controls walked at self-selected speed. Power curves for each lower limb
      joint were segmented into concentric and eccentric sources of muscle power and
      transfer/no-transfer modes to calculate MEEs during stance. FINDINGS: MEEs were
      lower in the stroke group on the affected side compared to the less affected side
      and compared to controls. Specifically, the affected plantarflexors transferred
      less energy distally via concentric action in late stance compared to the less
      affected side. However, the stroke group generated greater energy at the ankle in
      the absence of transfer compared to controls. Less concentrically transferred
      energy through midstance and absorbed in late stance was evident by the knee
      extensors bilaterally in stroke. At the hip, the total energy (no transfer) was
      reduced on the affected side. Classifying stroke subjects by walking speed
      (<.6m/s, >.6m/s) revealed disruptions in harnessing energy through motion and
      transfer energy across segments in the slower group. INTERPRETATION: The limited
      ability of those with stroke to exploit intersegmental energy transfer to
      optimize efficiency may limit endurance and functional independence.

PMID- 25582807
TI  - Sleep disruption and its effect on lymphocyte redeployment following an acute
      bout of exercise.
AB  - Sleep disruption and deprivation are common in contemporary society and have been
      linked with poor health, decreased job performance and increased life-stress. The
      rapid redeployment of lymphocytes between the blood and tissues is an archetypal
      feature of the acute stress response, but it is not known if short-term
      perturbations in sleep architecture affect lymphocyte redeployment. We examined
      the effects of a disrupted night sleep on the exercise-induced redeployment of
      lymphocytes and their subtypes. 10 healthy male cyclists performed 1h of cycling
      at a fixed power output on an indoor cycle ergometer, following a night of
      undisrupted sleep (US) or a night of disrupted sleep (DS). Blood was collected
      before, immediately after and 1h after exercise completion. Lymphocytes and their
      subtypes were enumerated using direct immunofluorescence assays and 4-colour flow
      cytometry. DS was associated with elevated concentrations of total lymphocytes
      and CD3(-)/CD56(+) NK-cells. Although not affecting baseline levels, DS augmented
      the exercise-induced redeployment of CD8(+) T-cells, with the naive/early
      differentiated subtypes (KLRG1(-)/CD45RA(+)) being affected most. While the
      mobilisation of cytotoxic lymphocyte subsets (NK cells, CD8(+) T-cells gammadelta
      T-cells), tended to be larger in response to exercise following DS, their
      enhanced egress at 1h post-exercise was more marked. This occurred despite
      similar serum cortisol and catecholamine levels between the US and DS trials. NK
      cells redeployed with exercise after DS retained their expression of perforin and
      Granzyme-B indicating that DS did not affect NK-cell 'arming'. Our findings
      indicate that short-term changes in sleep architecture may 'prime' the immune
      system and cause minor enhancements in lymphocyte trafficking in response to
      acute dynamic exercise. 

PMID- 25582808
TI  - Immune-related pathways including HLA-DRB1(*)13:02 are associated with panic
      disorder.
AB  - Panic disorder (PD) is an anxiety disorder characterized by panic attacks and
      anticipatory anxiety. Both genetic and environmental factors are thought to
      trigger PD onset. Previously, we performed a genome-wide association study (GWAS)
      for PD and focused on candidate SNPs with the lowest P values. However, there
      seemed to be a number of polymorphisms which did not reach genome-wide
      significance threshold due to their low allele frequencies and odds ratios, even
      though they were truly involved in pathogenesis. Therefore we performed pathway
      analyses in order to overcome the limitations of conventional single-marker
      analysis and identify associated SNPs with modest effects. Each pathway analysis
      indicated that pathways related to immunity showed the strongest association with
      PD (DAVID, P=2.08*10(-6); i-GSEA4GWAS, P<10(-3); ICSNPathway, P<10(-3)). Based on
      the results of pathway analyses and the previously performed GWAS for PD, we
      focused on and investigated HLA-B and HLA-DRB1 as candidate susceptibility genes
      for PD. We typed HLA-B and HLA-DRB1 in 744 subjects with PD and 1418 control
      subjects. Patients with PD were significantly more likely to carry HLA
      DRB1(*)13:02 (P=2.50*10(-4), odds ratio=1.54). Our study provided initial
      evidence that HLA-DRB1(*)13:02 and genes involved in immune-related pathways are
      associated with PD. Future studies are necessary to confirm these results and
      clarify the underlying mechanisms causing PD. 

PMID- 25582810
TI  - The Chicago face database: A free stimulus set of faces and norming data.
AB  - Researchers studying a range of psychological phenomena (e.g., theory of mind,
      emotion, stereotyping and prejudice, interpersonal attraction, etc.) sometimes
      employ photographs of people as stimuli. In this paper, we introduce the Chicago
      Face Database, a free resource consisting of 158 high-resolution, standardized
      photographs of Black and White males and females between the ages of 18 and 40
      years and extensive data about these targets. In Study 1, we report pre-testing
      of these faces, which includes both subjective norming data and objective
      physical measurements of the images included in the database. In Study 2 we
      surveyed psychology researchers to assess the suitability of these targets for
      research purposes and explored factors that were associated with researchers'
      judgments of suitability. Instructions are outlined for those interested in
      obtaining access to the stimulus set and accompanying ratings and measures.

PMID- 25582809
TI  - Heritability of compulsive Internet use in adolescents.
AB  - Over the past decades, Internet use has grown substantially, and it now serves
      people as a supportive tool that is used regularly and-in large parts of the
      world-inevitably. Some people develop problematic Internet use, which may lead to
      addictive behavior and it is becoming important to explore the risk factors for
      compulsive Internet use. Data were analyzed on compulsive Internet use [with the
      Compulsive Internet Use Scale (CIUS)] from 5247 monozygotic (MZ) and dizygotic
      (DZ) adolescent twins registered with the Netherlands Twin Register. The
      participants form a sample that is informative for genetic analyses, allowing the
      investigation of the causes of individual differences in compulsive Internet use.
      The internal consistency of the instrument was high and the 1.6-year test-retest
      correlation in a subsample (n = 902) was 0.55. CIUS scores increased slightly
      with age. Remarkably, gender did not explain variation in CIUS scores, as mean
      scores on the CIUS were the same in boys and girls. However, the time spent on
      specific Internet activities differed: boys spent more time on gaming, whereas
      girls spent more time on social network sites and chatting. The heritability
      estimates were the same for boys and girls: 48 percent of the individual
      differences in CIUS score were influenced by genetic factors. The remaining
      variance (52 percent) was due to environmental influences that were not shared
      between family members. Because a life without Internet is almost impossible
      nowadays, it is important to further explore the determinants of compulsive
      Internet use, including genetic risk factors.

PMID- 25582812
TI  - Lack of timely follow-up of abnormal imaging results and radiologists'
      recommendations.
AB  - PURPOSE: Abnormal imaging results may not always lead to timely follow-up. We
      tested whether certain aspects of communication in radiology reports influence
      the response of the referring providers, and hence follow-up on abnormal
      findings. METHODS: We focused on 2 communication-related items that we
      hypothesized could affect follow-up: expressions of doubt in the radiology
      report, and recommendations for further imaging. After institutional review board
      approval, we conducted a retrospective review of 250 outpatient radiology reports
      from a multispecialty ambulatory clinic of a tertiary-care Veterans Affairs
      facility. The selected studies included 92 cases confirmed to lack timely follow
      up (ie, further tests or consultations, treatment, and/or communication to the
      patient within 4 weeks), as determined in a previous study. An additional 158
      cases with documented timely follow-up served as controls. Doubt in the narrative
      was measured by the presence of key phrases (eg, "unable to exclude," "cannot
      exclude," "cannot rule out," "possibly," and "unlikely"), in the absence of which
      we used reviewer interpretation. A physician blinded to follow-up outcomes
      collected the data. RESULTS: Patients whose reports contained recommendations for
      further imaging were more likely to have been lost to follow-up at 4 weeks
      compared with patients without such recommendations (P = .01). Language in the
      report suggestive of doubt did not affect the timeliness of follow-up (P = .59).
      CONCLUSIONS: Abnormal imaging results with recommendations for additional imaging
      may be more vulnerable to lack of timely follow-up. Additional safeguards, such
      as tracking systems, should be developed to prevent failure to follow up on such
      results.

PMID- 25582813
TI  - The Psychology of Creativity.

PMID- 25582811
TI  - Moral foundations vignettes: a standardized stimulus database of scenarios based
      on moral foundations theory.
AB  - Research on the emotional, cognitive, and social determinants of moral judgment
      has surged in recent years. The development of moral foundations theory (MFT) has
      played an important role, demonstrating the breadth of morality. Moral psychology
      has responded by investigating how different domains of moral judgment are shaped
      by a variety of psychological factors. Yet, the discipline lacks a validated set
      of moral violations that span the moral domain, creating a barrier to
      investigating influences on judgment and how their neural bases might vary across
      the moral domain. In this paper, we aim to fill this gap by developing and
      validating a large set of moral foundations vignettes (MFVs). Each vignette
      depicts a behavior violating a particular moral foundation and not others. The
      vignettes are controlled on many dimensions including syntactic structure and
      complexity making them suitable for neuroimaging research. We demonstrate the
      validity of our vignettes by examining respondents' classifications of moral
      violations, conducting exploratory and confirmatory factor analysis, and
      demonstrating the correspondence between the extracted factors and existing
      measures of the moral foundations. We expect that the MFVs will be beneficial for
      a wide variety of behavioral and neuroimaging investigations of moral cognition. 

PMID- 25582814
TI  - Regioselective derivatizations of a tribrominated atropisomeric benzamide
      scaffold.
AB  - The enantioselective synthesis of atropisomeric, tribrominated benzamides and
      subsequent regioselective transformations to afford derivatized, axially chiral
      molecules is reported. The enantioenriched tribromides were carried through
      sequential Pd-catalyzed cross-coupling and lithium-halogen exchange with high
      regioselectivity and enantioretention. A variety of complexity-generation
      functional group installations were performed to create a library of homochiral
      benzamides. The potential utility of these molecules is demonstrated by using a
      phosphino benzamide derivative as an asymmetric ligand in a Pd-catalyzed allylic
      alkylation. 

PMID- 25582815
TI  - Corporoplasty using buccal mucosa graft in Peyronie disease: is it a first
      choice?
AB  - OBJECTIVE: To assesses the surgical and functional efficacy of corporoplasty with
      buccal mucosa graft, patients and partner's satisfaction, and the low cost of
      this operation. Biocompatible tissues are frequently used during corporoplasty,
      but they are expensive and often do not match the thickness and elasticity of the
      tunica albuginea, leading to fibrosis and scar retraction. Buccal mucosa graft is
      not usually emphasized in many review articles and clinical studies are limited.
      METHODS: Thirty-two patients with stable disease and normal erections were
      included in this retrospective study. All patients underwent corporoplasty with
      plaque incision and buccal mucosa graft. Preoperative International Index of
      Erectile Function (IIEF) questionnaire and penile duplex ultrasonographies with
      measurement of curvature were conducted. At 6 and 12 months postoperatively,
      patients answered the IIEF and the Patient Global Impression of Improvement
      questionnaires. Patient and partner satisfaction were recorded at all subsequent
      visits. RESULTS: Thirty-two patients underwent corporoplasty between 2006 and
      2013, and no major complications developed in any patient. After 1 year,
      curvature relapse was present in 1 patient (3.5%), and 1 patient had slight
      erectile dysfunction. IIEF values had significantly improved 1 year after surgery
      (P = .031). Patient satisfaction was 85% on the Patient Global Impression of
      Improvement questionnaire. Twenty-five of 28 partners were satisfied (90%). Data
      analysis confirmed the stability of the IIEF score in 16 patients after 2 years
      (mean IIEF score, 21.3). CONCLUSION: Corporoplasty with buccal mucosa graft is
      easy to perform and represents a good treatment choice for most forms of Peyronie
      disease with curvature preventing penetration and sexual intercourse.

PMID- 25582816
TI  - Effectiveness of acupuncture on chronic prostatitis-chronic pelvic pain syndrome
      category IIIB patients: a prospective, randomized, nonblinded, clinical trial.
AB  - OBJECTIVE: To compare the acupuncture treatment and the medical treatment with
      antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) on pain control,
      urinary symptoms, and quality of life of category IIIB chronic prostatitis
      chronic pelvic pain syndrome (CP-CPPS). METHODS: From November 2008 to May 2009,
      54 male patients with category IIIB CP-CPPS were randomly divided into 2 groups:
      the medical treatment group (group 1, n = 28) and the acupuncture treatment group
      (group 2, n = 26). Group 1 took levofloxacin 500 mg daily and ibuprofen 200 mg
      twice a day for 6 weeks. In the acupuncture group (group 2), bilateral BL32
      (Ciliao) and BL33 (Zhongliao) acupoints were used to stimulate the sacral nerve
      using an electrical pulse generator, twice a week for 7 weeks. The change in
      National Institutes of Health Chronic Prostatitis Symptom Index scores from the
      baseline to the end of the treatment was observed. RESULTS: The mean follow-up
      was 28 weeks from the baseline (range, 20-43 weeks). In acupuncture group,
      reduction of pain, urinary symptoms, quality of life, and total National
      Institutes of Health Chronic Prostatitis Symptom Index score was higher compared
      with the medical group. CONCLUSION: However the treatment of CP-CPPS is
      challenging and difficult for the urologists. This clinical study showed that the
      acupuncture treatment is a safe and effective treatment of category IIIB CP-CPPS.

PMID- 25582817
TI  - A rapid progression of disease after surgical excision of a malignant rhabdoid
      tumor of the bladder.
AB  - Extrarenal malignant rhabdoid tumors (MRTs) are rare tumors with a poor
      prognosis. Five-year overall survival for patients with MRTs is poor at
      approximately 20%.(1) There are 5 case reports of histologically confirmed
      primary MRT of the bladder in pediatric patients. Herein, we report a case of an
      MRT of the bladder in a 14-year-old boy and discuss the preoperative evaluation,
      treatment options, and possible etiologies of metastasis after radical surgery.

PMID- 25582818
TI  - Thiel embalming method for cadaver preservation: a review of new training model
      for urologic skills training.
AB  - The use of endourology training models is on the rise. Surgical practice is
      moving toward a more minimally invasive approach and deficits in surgical
      exposure by enforcement of the European Working Time Directive call for
      simulation models to be anatomically sound. Thiel-embalmed cadavers have been
      found to demonstrate efficacy in tissue quality, elasticity, and handling in
      addition to playing a role in teaching and training. This review summarizes the
      current status of the Thiel method and its role in urologic skills training. 

PMID- 25582819
TI  - A nanogold resonance Rayleigh scattering method for determination of trace As
      based on the hydride nanoreaction.
AB  - In H2 SO4 solution, As(III) was reduced to arsine (AsH3 ) by NaBH4 , and was
      absorbed in HAuCl4 solution to form nanogold particles (NGs) that exhibited a
      resonance Rayleigh scattering (RRS) effect at 370 nm. Under the selected
      conditions, when the As(III) concentration increased the RRS peak also increased
      due to the formation of more NGs. There was a linear correlation between RRS
      intensity and As(III) concentration in the range 6-1000 ng/mL, with a detection
      limit of 3 ng/mL. This new hydride generation-nanogold reaction RRS (HG-NG RRS)
      method was applied to determine trace amounts of As in milk samples, with
      satisfactory results.

PMID- 25582820
TI  - Regioselective electrophilic borylation of haloarenes.
AB  - Haloarenes undergo direct borylation using amine : BCl3 : AlCl3 in the ratio of 1
      : 1 : 2. After esterification the pinacol boronate esters are isolated in good
      yield with regioselectivity controlled by steric and electronic effects. 

PMID- 25582821
TI  - Endoscopic transnasal resection of Eustachian-tube dermoid in a new-born infant.
AB  - INTRODUCTION: Dermoids of the Eustachian tube are rare benign developmental
      tumours that typically occur in female children. General consensus of
      classification and nomenclature has still not been reached. The treatment of
      choice consists of a radical surgical excision. Several approaches have been
      described and few cases are reported in literature. A gross total resection is
      now safely achievable through an endoscopic mini-invasive approach. MATERIALS AND
      METHODS: We have reported a case of dermoid pedicled in the left Eustachian tube
      and resected with a pure endoscopic transnasal approach. A review of the
      literature was performed. CASE STUDY: The aim of this paper is to present the
      first case of pure endoscopic transnasal resection in a 4-day-old infant as
      emergency treatment of Eustachian tube dermoid presenting an acute respiratory
      failure at birth. CONCLUSION: The endoscopic transnasal resection is a safe and
      feasible technique in selected dermoids of the Eustachian tube, when the middle
      ear is not involved. This approach could be used also in new-born children,
      decreasing the morbidity of the classic surgical treatment and avoiding the risk
      of craniofacial alterations.

PMID- 25582822
TI  - On the rheology of pendular gels and morphological developments in paste-like
      ternary systems based on capillary attraction.
AB  - We investigate capillary bridging-induced gelation phenomena in silica particle
      suspensions and pastes, where a particle-wetting fluid is added as the third
      component. Increasing the wetting fluid loading in the ternary system induces a
      morphological transition from a pendular network to compact capillary aggregates
      network, with an intermediate funicular state. To our knowledge, the formation of
      percolated structures from compact capillary aggregates when the volume fraction
      of a wetting fluid approaches that of the particles is unprecedented. Such
      structures appear to result from the arrested coalescence of compact capillary
      aggregates due to the balance between the Laplace pressure and solid-like
      properties (yield stress, elasticity) of the aggregates. Shear-induced yielding
      of the ternary systems, linked to their percolating nature, is strongly
      influenced by the amount of wetting fluid phase. A non-monotonic dependence of
      the yield stress on the amount of wetting fluid is found, with the maximum yield
      stress obtained for a wetting fluid-to-particle volume fraction ratio of 0.2-0.3.
      For pendular systems, linear viscoelastic properties display a soft glassy
      rheological behavior above the percolation threshold (around 4 vol% particles),
      and complex viscosity data can be scaled using the high frequency plateau value,
      as well as a single characteristic relaxation time, which decreases when the
      particle concentration is increased. In addition, the particle concentration
      dependence of the yielding transition in the pendular regime appears to be
      efficiently described by two parameters extracted from the steady state flow
      curves: the yield stress and the limiting viscosity at a high shear rate.
      Although these non-colloidal networks result from flow-driven assembly, the
      scaling laws for our pendular gels are reminiscent of colloidal gels with a
      fractal geometry. Our studies pinpoint new pathways to create physical gels where
      the interparticle attraction strength is determined by capillary interactions. 

PMID- 25582823
TI  - Can you ask? We just did! Assessing sexual function and concerns in patients
      presenting for initial gynecologic oncology consultation.
AB  - OBJECTIVES: To describe patterns of response to, and assess sexual function and
      activity elicited by, a self-administered assessment incorporated into a new
      patient intake form for gynecologic oncology consultation. METHODS: A cross
      sectional study of patients presenting to a single urban academic medical center
      between January 2010 and September 2012. New patients completed a self
      administered intake form, including six brief sexual activity and function items.
      These items, along with abstracted medical record data, were descriptively
      analyzed. Logistic regression was used to assess the association between sexual
      activity and function and disease status, adjusting for age. RESULTS: Median age
      was 50 years (range 18-91, N=499); more than half had a final diagnosis of
      cancer. Most patients completed all sex-related items on the intake form; 98%
      answered at least one. Among patients who were sexually active in the prior 12
      months (57% with cancer, 64% with benign disease), 52% indicated on the intake
      form having, during that period, a sexual problem lasting several months or more.
      Of these, 15% had physician documentation of the sexual problem. Eighteen women
      were referred for care. Providers reported no patient complaints about the
      inclusion of sexual items on the intake form. CONCLUSIONS: Nearly all new
      patients presenting for gynecologic oncology consultation answered self
      administered items to assess sexual activity and function. Further study is
      needed to determine the role of pre-treatment identification of sexual function
      concerns in improving sexual outcomes associated with cancer diagnosis and
      treatment.

PMID- 25582825
TI  - Prevalence of hepatitis B infection in women delivering at a community health
      centre in Dili, Timor-Leste and discussion of programmatic challenges.
AB  - BACKGROUND: Limited data regarding prevalence of hepatitis B virus infection in
      Timor-Leste exist. METHODS: An observational study of hepatitis B surface antigen
      (HBsAg) results of women delivering at Bairo Pite Clinic in Dili, Timor-Leste was
      carried out. RESULTS: Of the 781 women included in the study, 80.5% (626/777) of
      women who had accessed antenatal care had been tested for HBsAg, of whom 2.2%
      (14/626) were positive. Of the remaining women, 83.2% (129/155) received a test
      at the time of delivery, of whom 5.4% (7/129) were positive. Overall prevalence
      of HBsAg positivity was 2.8% (21/755). CONCLUSIONS: Further studies are urgently
      needed to establish the prevalence of HBV infection in Timor-Leste, particularly
      in pregnant women. Findings from this study suggest that routine HBV immunisation
      of newborns should be instituted promptly.

PMID- 25582826
TI  - In reference to Does Body Mass Index Predict Tracheal Airway Size?

PMID- 25582824
TI  - Enhancing antitumor efficacy of chimeric antigen receptor T cells through
      constitutive CD40L expression.
AB  - Adoptive cell therapy with genetically modified T cells expressing a chimeric
      antigen receptor (CAR) is a promising therapy for patients with B-cell acute
      lymphoblastic leukemia. However, CAR-modified T cells (CAR T cells) have mostly
      failed in patients with solid tumors or low-grade B-cell malignancies including
      chronic lymphocytic leukemia with bulky lymph node involvement. Herein, we
      enhance the antitumor efficacy of CAR T cells through the constitutive expression
      of CD40 ligand (CD40L, CD154). T cells genetically modified to constitutively
      express CD40L (CD40L-modified T cells) demonstrated increased proliferation and
      secretion of proinflammatory TH1 cytokines. Further, CD40L-modified T cells
      augmented the immunogenicity of CD40(+) tumor cells by the upregulated surface
      expression of costimulatory molecules (CD80 and CD86), adhesion molecules (CD54,
      CD58, and CD70), human leukocyte antigen (HLA) molecules (Class I and HLA-DR),
      and the Fas-death receptor (CD95). Additionally, CD40L-modified T cells induced
      maturation and secretion of the proinflammatory cytokine interleukin-12 by
      monocyte-derived dendritic cells. Finally, tumor-targeted CD19-specific CAR/CD40L
      T cells exhibited increased cytotoxicity against CD40(+) tumors and extended the
      survival of tumor-bearing mice in a xenotransplant model of CD19(+) systemic
      lymphoma. This preclinical data supports the clinical application of CAR T cells
      additionally modified to constitutively express CD40L with anticipated enhanced
      antitumor efficacy. 

PMID- 25582827
TI  - A bio-inspired total synthesis of tetrahydrofuran lignans.
AB  - Lignan natural products comprise a broad spectrum of biologically active
      secondary metabolites. Their structural diversity belies a common biosynthesis,
      which involves regio- and chemoselective oxidative coupling of propenyl phenols.
      Attempts to replicate this oxidative coupling have revealed significant
      challenges for controlling selectivity, and these challenges have thus far
      prevented the development of a unified biomimetic route to compounds of the
      lignan family. A practical solution is presented that hinges on oxidative ring
      opening of a diarylcyclobutane to intercept a putative biosynthetic intermediate.
      The effectiveness of this approach is demonstrated by the first total synthesis
      of tanegool in 4 steps starting from ferulic acid, as well as a concise synthesis
      of the prototypical furanolignan pinoresinol. 

PMID- 25582829
TI  - Creation of a Death by Suicide.
AB  - Background: Suicide research acknowledges the negotiated nature of a coroner's
      verdict of suicide. However, the process by which those who are bereaved come to
      determine that a death was a suicide has received little attention. Aims: To
      explore how young adults come to conceptualize their friends' deaths as suicides.
      Method: In-depth interviews were undertaken with 12 young people whose friends
      had died by apparent suicides. Interviews were analyzsed using interpretative
      phenomenological analysis. Results: Few of the participants attended the inquest,
      and most placed little value on the verdict given to the death by the coroner.
      However, participants used processes and definitions similar to the coroners' to
      explore and create meaning from their friend's final thoughts and actions in
      order to determine whether he/she meant to end their life. Conclusion: This
      research contributes to our understanding of the profound impact of death by
      suicide and the negotiated nature of participants' understandings of the death.
      The findings can assist in understanding how the bereaved may be supported.

PMID- 25582828
TI  - Cell entry of bovine ephemeral fever virus requires activation of Src-JNK-AP1 and
      PI3K-Akt-NF-kappaB pathways as well as Cox-2-mediated PGE2 /EP receptor
      signalling to enhance clathrin-mediated virus endocytosis.
AB  - Although we have previously demonstrated that cell entry of bovine ephemeral
      fever virus (BEFV) follows a clathrin-mediated and dynamin 2-dependent
      endocytosis pathway, the cellular mechanism mediating virus entry remains
      unknown. Here, we report that BEFV triggers simultaneously Src-JNK-AP1 and PI3K
      Akt-NF-kappaB signalling pathways in the stage of virus binding to induce
      clathrin and dynamin 2 expressions, while vesicular stomatitis virus only
      activates Src-JNK signalling to enhance its entry. Activation of these pathways
      by ultraviolet-inactivated BEFV suggests a role for virus binding but not viral
      internalization and gene expression. By blocking these signalling pathways with
      specific inhibitors, BEFV-induced expressions of clathrin and dynamin 2 were
      significantly diminished. By labelling BEFV with 3,3'-dilinoleyloxacarbocyanine
      perchlorate to track viral entry, we found that virus entry was hindered by both
      Src and Akt inhibitors, suggesting that these signalling pathways are crucial for
      efficient virus entry. In addition, BEFV also triggers Cox-2-catalysed
      prostaglandin E2 (PGE2) synthesis and induces expressions of G-protein-coupled E
      prostanoid (EP) receptors 2 and 4, leading to amplify signal cascades of Src-JNK
      AP1 and PI3K-Akt-NF-kappaB, which elevates both clathrin and dynamin 2
      expressions. Furthermore, pretreatment of cells with adenylate cyclase (cAMP)
      inhibitor SQ22536 reduced BEFV-induced Src phosphorylation as well as clathrin
      and dynamin 2 expressions. Our findings reveal for the first time that BEFV
      activates the Cox-2-mediated PGE2/EP receptor signalling pathways, further
      enhancing Src-JNK-AP1 in a cAMP-dependent manner and PI3K-Akt-NF-kappaB in a cAMP
      independent manner. Accordingly, BEFV stimulates PGE2/EP receptor signalling
      amplifying Src-JNK-AP1 and PI3K-Akt-NF-kappaB pathways in an autocrine or
      paracrine fashion to enhance virus entry.

PMID- 25582830
TI  - Hospital-Treated Deliberate Self-Harm in the Western Area of Northern Ireland.
AB  - Background: The Northern Ireland Registry of Deliberate Self-Harm was established
      as an outcome of the Northern Ireland Suicide Prevention Strategy and Action Plan
      - Protect Life, beginning in the Western Health and Social Care Trust area. Aims:
      The study aimed to establish the incidence of hospital-treated deliberate self
      harm in the Western Area of Northern Ireland, and to explore the profile of such
      presentations. Method: Deliberate self-harm presentations made to the three
      hospital emergency departments operating in the area during the period 2007-2012
      were recorded. Results: There were 8,175 deliberate self-harm presentations by
      4,733 individuals. Respectively, the total, male, and female age-standardized
      incidence rate was 342, 320, and 366 per 100,000 population. City council
      residents had a far higher self-harm rate. The peak rate for women was among 15
      19-year-olds (837 per 100,000) and for men was among 20-24-year-olds (809 per
      100,000). Risk of repetition was higher in 35-44-year-old patients if self
      cutting was involved, but was most strongly associated with the number of
      previous self-harm presentations. Conclusion: The incidence of hospital-treated
      self-harm in Northern Ireland is far higher than in the Republic of Ireland and
      more comparable to that in England.

PMID- 25582831
TI  - Suicide in Slovenia Between 1997 and 2010.
AB  - Background: With an average suicide rate of approximately 30 per 100,000,
      Slovenia has been regarded as a country with a high suicide rate. In the last
      decade, however, the suicide rate has gradually decreased to 20.3 per 100,000.
      Aim: To undertake an analysis of the suicide rate and its characteristics between
      1997 and 2010 and to establish whether preventive activities had a significant
      effect on the suicide rate in the period studied. Method: Data on all 7,317
      completed suicides between 1997 and 2010 were obtained from the National
      Mortality Database. Trends over this period were assessed separately for gender,
      age, method of suicide, and regional distribution. Data on implemented suicide
      preventive activities were assessed via regional Public Health Institutes.
      Results: The suicide rate declined in both genders and in all age groups, except
      in males aged 10-19 years. The most frequently used method in both genders was
      hanging. Regions with the highest suicide rate are concentrated in the eastern
      part of Slovenia. The suicide rate significantly decreased in six regions, but no
      firm association with preventive activities could be established. Conclusion:
      Suicide in Slovenia declined significantly during the study period. Preventive
      activities appear not to have had any notable effect on this decline.

PMID- 25582832
TI  - Military Service and Suicidal Thoughts and Behaviors in a National Sample of
      College Students.
AB  - Background: As a result of the post-9/11 GI Bill, increasing numbers of veterans
      are enrolling in college. However, little is known regarding suicidal outcomes
      among this group. In prior research, college student veterans reported high rates
      of suicidal ideation and attempt. Nonetheless, no research has examined whether
      military service is associated with increased suicide risk among college
      students. Aims: Our primary aims were to examine whether a history of military
      service was related to past-year suicidal ideation, plan, and attempt among
      college students. On the basis of previous research with college students, we
      hypothesized that students with a history of military service (i.e., current or
      prior) would report a higher percentage of past-year suicidal ideation, plan, and
      attempt. Our secondary aims were to examine the associations between military
      service and major depression and nonsuicidal self-injury. Method: Our sample
      included 3,290 college students with and without a history of military service
      who participated in the Healthy Minds Study in 2011 and 2012. Results: Military
      service was not significantly associated with past-year suicidal ideation, plan,
      or attempt. Students without a history of military service were more likely to
      report nonsuicidal self-injury. There was no significant difference in screening
      positive for major depression. Conclusions: These findings conflict with previous
      research that identified student veterans as being at elevated risk.

PMID- 25582833
TI  - Astrocyte and microvascular imaging in awake animals using two-photon microscopy.
AB  - Neurovascular coupling is an important control mechanism in CBF regulation. New
      insights into the integrated relationship between synaptic activity, astrocytes
      Ca(2+) , and cerebral blood vessels using two-photon fluorescence imaging are
      slowly emerging. Here, we provide a brief overview of the current understandings
      and controversies regarding astrocytes in activity-dependent vasodilation. We
      highlight the key advantages and disadvantages of the in vitro and in vivo
      methodologies used to study this topic. In particular, we emphasize some of the
      drawbacks of acute brain slices as well as the confounding effects of anesthesia
      in in vivo preparations. To overcome these limitations, we discuss an emerging
      and important trend in imaging cell Ca(2+) and blood flow control in awake and
      behaving animals. This new approach may help resolve existing controversies on
      astrocyte control of arteriole diameter by providing a more physiologically
      relevant preparation to study CBF regulation. 

PMID- 25582834
TI  - Isolation and genome characterization of a novel duck Tembusu virus with a 74
      nucleotide insertion in the 3' non-translated region.
AB  - During investigations into the outbreak of duck Tembusu virus (DTMUV) infection
      in 2011 in China, a DTMUV strain (DTMUV-AH2011) was isolated from the affected
      ducks. The length of the genome of the DTMUV-AH2011 strain was found to be 11,064
      nucleotides and to possess 10,278 nucleotides of one open reading frame (ORF),
      flanked by 94 nucleotides of the 5' non-translated region (NTR) and 692
      nucleotides of the 3' NTR. In comparison with five fully sequenced TMUV genomes,
      the genome of DTMUV-AH2011 had a 74 nucleotide insertion in the 3' NTR.
      Comparison of the DTMUV-AH2011 fully deduced amino acid sequences with those of
      other Tembusu virus strains reported recently in China showed they had a highly
      conserved polyprotein precursor, sharing 98.9% amino acid identities, at least.
      The overall divergences of amino acid substitutions were randomly distributed
      among viral proteins except for the protein NS4B, the protein NS4B was unchanged.
      Knowledge of the biological characters of DTMUV and the potential role of the
      insertion in the 3' NTR in RNA replication will be useful for further studies of
      the mechanisms of virus replication and pathogenesis. 

PMID- 25582835
TI  - Pediatric tectal plate gliomas: a review of clinical outcomes, endocrinopathies,
      and neuropsychological sequelae.
AB  - Pediatric tectal plate gliomas are indolent slow-growing gliomas that often
      present with increased intracranial pressure or incidentally on routine brain
      imaging. We investigated clinical outcomes, endocrinopathies, and
      neuropsychological sequelae associated with tectal plate gliomas. Twenty-six
      patients with tectal plate glioma were identified in a 20-year retrospective
      review. Clinical outcomes, treatments, endocrine function, neuropsychological
      testing outcomes and radiographic imaging were reviewed for possible signs
      correlating with tumor progression. Among 26 patients, 19 presented with signs or
      symptoms of increased intracranial pressure (73 %) versus an incidental finding
      in 7 (27 %). Median follow-up was 46 months (range 8-143 months). Six of 26 (23
      %) experienced progressive disease after diagnosis. Five of 26 (19 %) required
      more than one surgical procedure due to failure of initial endoscopic third
      ventriculostomy. Seven of 26 had history of endocrine dysfunction, of which, five
      presented with endocrine dysfunction (precocious puberty or short stature), 1
      developed menstrual irregularities after surgical intervention and 1 had
      preexisting pan hypopituitarism. Of 12 patients with available neuropsychological
      testing, eleven had at least one indicator of executive functioning in the low
      average to impaired range. While tectal plate gliomas have been considered
      indolent tumors that are rarely progressive, 23 % of patients in our cohort
      experienced disease progression and required further therapy. Neurocognitive
      deficits may occur, while endocrine deficiency is uncommon. Regular
      multidisciplinary oncology follow-up, routine monitoring with MRI and formal
      neurocognitive evaluation are imperative to provide early recognition of disease
      progression or recurrent hydrocephalus and to improve school functioning in this
      population.

PMID- 25582836
TI  - Wide field-of-view fluorescence imaging of coral reefs.
AB  - Coral reefs globally are declining rapidly because of both local and global
      stressors. Improved monitoring tools are urgently needed to understand the
      changes that are occurring at appropriate temporal and spatial scales. Coral
      fluorescence imaging tools have the potential to improve both ecological and
      physiological assessments. Although fluorescence imaging is regularly used for
      laboratory studies of corals, it has not yet been used for large-scale in situ
      assessments. Current obstacles to effective underwater fluorescence surveying
      include limited field-of-view due to low camera sensitivity, the need for
      nighttime deployment because of ambient light contamination, and the need for
      custom multispectral narrow band imaging systems to separate the signal into
      meaningful fluorescence bands. Here we describe the Fluorescence Imaging System
      (FluorIS), based on a consumer camera modified for greatly increased sensitivity
      to chlorophyll-a fluorescence, and we show high spectral correlation between
      acquired images and in situ spectrometer measurements. This system greatly
      facilitates underwater wide field-of-view fluorophore surveying during both night
      and day, and potentially enables improvements in semi-automated segmentation of
      live corals in coral reef photographs and juvenile coral surveys. 

PMID- 25582837
TI  - Automatic recognition of cardiac arrhythmias based on the geometric patterns of
      Poincare plots.
AB  - The Poincare plot emerges as an effective tool for assessing cardiovascular
      autonomic regulation. It displays nonlinear characteristics of heart rate
      variability (HRV) from electrocardiographic (ECG) recordings and gives a global
      view of the long range of ECG signals. In the telemedicine or computer-aided
      diagnosis system, it would offer significant auxiliary information for diagnosis
      if the patterns of the Poincare plots can be automatically classified. Therefore,
      we developed an automatic classification system to distinguish five geometric
      patterns of the Poincare plots from four types of cardiac arrhythmias. The
      statistics features are designed on measurements and an ensemble classifier of
      three types of neural networks is proposed. Aiming at the difficulty to set a
      proper threshold for classifying the multiple categories, the threshold selection
      strategy is analyzed. 24 h ECG monitoring recordings from 674 patients, which
      have four types of cardiac arrhythmias, are adopted for recognition. For
      comparison, Support Vector Machine (SVM) classifiers with linear and Gaussian
      kernels are also applied. The experiment results demonstrate the effectiveness of
      the extracted features and the better performance of the designed classifier. Our
      study can be applied to diagnose the corresponding sinus rhythm and arrhythmia
      substrates disease automatically in the telemedicine and computer-aided diagnosis
      system. 

PMID- 25582839
TI  - Terminal ileal intubation and biopsy in routine colonoscopy practice.
AB  - This special report focuses on the current literature regarding the utility of
      terminal ileal (TI) intubation and biopsy. The authors reviewed the literature
      regarding the clinical benefit of TI intubation at the time of colonoscopy and
      also the evidence for TI intubation as a colonoscopy quality indicator. TI
      intubation is useful to identify ileal diseases such as Crohn's disease and
      additionally as a means of confirming colonoscopy completion when classical
      caecal landmarks are not confidently seen. Previous studies have demonstrated
      that TI intubation has variable yield but may be more useful in patients
      presenting with diarrhea. Reported rates of TI intubation at colonoscopy vary.
      The authors demonstrate that terminal ileoscopy is feasible in clinical practice
      and sometimes yields additional clinical information. Additionally it may be used
      as an indicator of colonoscopy completion. It may be particularly helpful when
      investigating patients with diarrhea, abnormalities seen on other imaging
      modalities and patients with suspected Crohn's disease. TIs reported as normal at
      endoscopy have a low yield when biopsied; however, biopsies from abnormal-looking
      TIs demonstrate a higher yield and have greater diagnostic value. 

PMID- 25582838
TI  - Immobilized IL-8 Triggers Phagocytosis and Dynamic Changes in Membrane
      Microtopology in Human Neutrophils.
AB  - The interaction of leukocytes with surface bound ligands can be limited by the
      location of the molecules relative to the surface topology of the cell. In this
      report, we examine the dynamic response of neutrophils to IL-8-fractalkine
      chimera immobilized on bead surfaces, taking into account changes in receptor
      occupancy resulting from changes in surface topography. As a readout for receptor
      signaling, we observe the dynamics of calcium release in neutrophils following
      contact with the IL-8 coated surface. After a delay that depended on the initial
      area of contact and the surface density of IL-8, the cell began to phagocytose
      the IL-8 coated bead. This appeared to be a pre-requisite for release of calcium,
      which typically followed shortly after the initiation of phagocytosis. In
      separate experiments, effective kinetic coefficients for the formation of bonds
      between immobilized IL-8 and receptors on the cell surface were determined. Using
      these coefficients, we were able to estimate the number of bound receptors in the
      nascent contact zone. Kinetic modeling of the signaling response predicted that
      cell spreading and a concomitant increase in the density of occupied receptors
      would be required for the experimentally observed calcium dynamics. Postulating
      that there is an increase in receptor occupancy resulting from smoothing of the
      cell surface as it is stretched over the bead enabled us to obtain model
      predictions consistent with experimental observations. This study reveals the
      likely importance of membrane microtopology as a rate-limiting property and
      potential means of regulation of cell responses stimulated by two-dimensional
      surface interactions. 

PMID- 25582840
TI  - Good sensitivity and specificity of ultrasound for detecting pseudotumors in 83
      failed metal-on-metal hip replacements.
AB  - BACKGROUND AND PURPOSE: Ultrasound is used for imaging of pseudotumors associated
      with metal-on-metal (MoM) hips. Ultrasound has been compared with magnetic
      resonance imaging, but to date there have been no studies comparing ultrasound
      findings and revision findings. METHODS: We evaluated the sensitivity and
      specificity of preoperative ultrasound for detecting pseudotumors in 82 patients
      with MoM hip replacement (82 hips). Ultrasound examinations were performed by 1
      of 3 musculoskeletal radiologists, and pseudotumors seen by ultrasound were
      retrospectively classified as fluid-filled, mixed-type, or solid. Findings at
      revision surgery were retrieved from surgical notes and graded according to the
      same system as used for ultrasound findings. RESULTS: Ultrasound had a
      sensitivity of 83% (95% CI: 63-93) and a specificity of 92% (CI: 82-96) for
      detecting trochanteric region pseudotumors, and a sensitivity of 79% (CI: 62-89)
      and a specificity of 94% (CI: 83-98) for detecting iliopsoas-region pseudotumors.
      Type misclassification of pseudotumors found at revision occurred in 8 of 23 hips
      in the trochanteric region and in 19 of 33 hips in the iliopsoas region.
      INTERPRETATION: Despite the discrepancy in type classification between ultrasound
      and revision findings, the presence of pseudotumors was predicted well with
      ultrasound in our cohort of failed MoM hip replacements.

PMID- 25582841
TI  - Secretory production of tetrameric native full-length streptavidin with
      thermostability using Streptomyces lividans as a host.
AB  - BACKGROUND: Streptavidin is a tetrameric protein derived from Streptomyces
      avidinii, and has tight and specific biotin binding affinity. Applications of the
      streptavidin-biotin system have been widely studied. Streptavidin is generally
      produced using protein expression in Escherichia coli. In the present study, the
      secretory production of streptavidin was carried out using Streptomyces lividans
      as a host. RESULTS: In this study, we used the gene encoding native full-length
      streptavidin, whereas the core region is generally used for streptavidin
      production in E. coli. Tetrameric streptavidin composed of native full-length
      streptavidin monomers was successfully secreted in the culture supernatant of S.
      lividans transformants, and had specific biotin binding affinity as strong as
      streptavidin produced by E. coli. The amount of Sav using S. lividans was about 9
      times higher than using E. coli. Surprisingly, streptavidin produced by S.
      lividans exhibited affinity to biotin after boiling, despite the fact that
      tetrameric streptavidin is known to lose its biotin binding ability after brief
      boiling. CONCLUSION: We successfully produced a large amount of tetrameric
      streptavidin as a secretory-form protein with unique thermotolerance.

PMID- 25582842
TI  - Using transcriptomics to guide lead optimization in drug discovery projects:
      Lessons learned from the QSTAR project.
AB  - The pharmaceutical industry is faced with steadily declining R&D efficiency which
      results in fewer drugs reaching the market despite increased investment. A major
      cause for this low efficiency is the failure of drug candidates in late-stage
      development owing to safety issues or previously undiscovered side-effects. We
      analyzed to what extent gene expression data can help to de-risk drug development
      in early phases by detecting the biological effects of compounds across disease
      areas, targets and scaffolds. For eight drug discovery projects within a global
      pharmaceutical company, gene expression data were informative and able to support
      go/no-go decisions. Our studies show that gene expression profiling can detect
      adverse effects of compounds, and is a valuable tool in early-stage drug
      discovery decision making. 

PMID- 25582844
TI  - Viologen-templated arrays of cucurbit[7]uril-modified iron-oxide nanoparticles.
AB  - Magnetic and fluorescent assemblies of iron-oxide nanoparticles (NPs) were
      constructed by threading a viologen-based ditopic ligand, DPV(2+), into the
      cavity of cucurbituril (CB[7]) macrocycles adsorbed on the surface of the NPs.
      Evidence for the formation of 1:2 inclusion complexes that involve DPV(2+) and
      two CB[7] macrocycles was first obtained in solution by (1)H NMR and emission
      spectroscopy. DPV(2+) was found to induce self-assembly of nanoparticle arrays
      (DPV(2+)?CB[7]NPs) by bridging CB[7] molecules on different NPs. The resulting
      viologen-crosslinked iron-oxide nanoparticles exhibited increased saturation
      magnetization and emission properties. This facile supramolecular approach to NP
      self-assembly provides a platform for the synthesis of smart and innovative
      materials that can achieve a high degree of functionality and complexity and that
      are needed for a wide range of applications.

PMID- 25582843
TI  - The neurite growth inhibitory effects of soluble TNFalpha on developing
      sympathetic neurons are dependent on developmental age.
AB  - During development, the growth of neural processes is regulated by an array of
      cellular and molecular mechanisms which influence growth rate, direction and
      branching. Recently, many members of the TNF superfamily have been shown to be
      key regulators of neurite growth during development. The founder member of this
      family, TNFalpha can both promote and inhibit neurite growth depending on the
      cellular context. Specifically, transmembrane TNFalpha promotes neurite growth,
      while soluble TNFalpha inhibits it. While the growth promoting effects of
      TNFalpha are restricted to a defined developmental window of early postnatal
      development, whether the growth inhibitory effects of soluble TNFalpha occur
      throughout development is unknown. In this study we used the extensively studied,
      well characterised neurons of the superior cervical ganglion to show that the
      growth inhibitory effects of soluble TNFalpha are restricted to a specific period
      of late embryonic and early postnatal development. Furthermore, we show that this
      growth inhibitory effect of soluble TNFalpha requires NF-kappaB signalling at all
      developmental stages at which soluble TNFalpha inhibits neurite growth. These
      findings raise the possibility that increases in the amount of soluble TNFalpha
      in vivo, for example as a result of maternal inflammation, could negatively
      affect neurite growth in developing neurons at specific stages of development. 

PMID- 25582846
TI  - Testosterone therapy and risk of myocardial infarction: a pharmacoepidemiologic
      study.
AB  - BACKGROUND: Recent studies have provided conflicting and controversial results
      about the risk of cardiovascular events, including myocardial infarction (MI),
      with testosterone replacement therapy (TRT). The potential adverse effects of
      different TRT formulations and duration of therapy on MI risk are unknown.
      METHODS: We performed a case-control study within a cohort of 934,283 men aged 45
      80 from the IMS LifeLink Health Plan Claims Database. For each case of MI, four
      controls were identified using density-based sampling. Rate ratios (RRs) were
      computed for current and past TRT users. As a sensitivity analysis, the risk of
      MI before and after the start of a first-time TRT prescription in the same
      patient was also computed. RESULTS: We identified 30,066 MI cases and 120,264
      corresponding controls. Current use of TRT was not associated with an increased
      risk of MI (RR 1.01, 95% confidence interval [CI] 0.89-1.16); first-time users
      did show an increased risk (RR 1.41, 95% CI 1.06-1.87; number needed to harm
      305). There was no association between MI and past TRT users and no differences
      among the different formulations. The RRs for current use and first-time use of
      TRT in men with a previous history of coronary artery disease were 1.05 (95% CI
      0.79-1.41) and 1.78 (95% CI 0.93-3.40), respectively. CONCLUSION: In this large
      observational study, an association between MI and past or current TRT use was
      not found. However, a statistically significant association was observed between
      first-time TRT exposure and MI, although the absolute risk was low.

PMID- 25582845
TI  - Length changes of scapholunate interosseous ligament at different wrist
      positions: an in vivo 3-dimension image study.
AB  - PURPOSE: The scapholunate interossous ligament (SLIL) has a critical role in
      maintaining the proper kinematic relationship between the scaphoid and the
      lunate. We hypothesize that the length of SLIL changes significantly at wrist
      full extension and during forearm rotation. The aim of this study was to
      investigate the length changes of SLIL at wrist full extension and forearm
      rotation in vivo. METHODS: Twelve volunteers were randomly divided to two groups.
      We obtained computed tomography scans of the wrists at different wrist positions.
      The three regions of the SLIL were measured and analyzed with computer modeling.
      RESULTS: The results showed that from the neutral to full extension of the wrist,
      the length of volar SLIL and volar, middle portions of the proximal SLIL
      increased significantly. The volar and proximal SLIL increased significantly in
      maximal forearm pronation. CONCLUSIONS: The lengths of the volar and proximal
      regions of SLIL increase substantially at wrist full extension, but only slightly
      at maximal forearm pronation. Clinically, wrist full extension may make the SLIL
      ligament vulnerable to disruption.

PMID- 25582847
TI  - Introduction of the Pill Pruner to acute medical care: a simple medication guide
      to control polypharmacy.
AB  - AIM: To assess the effect of a simple medication guide (the Pill Pruner) on the
      number of regular medications taken by older patients following medical
      admission. METHODS: In July 2009, following introduction of the Pill Pruner, we
      audited 500 consecutive older patients, recording the number of regular
      medications being taken on admission and discharge. Safety data included 90-day
      mortality and readmission rates. Medication numbers were compared to a similar
      audit undertaken in September 2008 and to a repeat audit in December 2009.
      RESULTS: The mean number of medications on admission (+/- SD) was 6.3 +/- 3
      versus 6.5 +/- 3 at discharge (P = 0.13). Number of discharge medications was
      decreased compared to September 2008 (7.7 +/- 4; P = 0.001) but similar to that
      for the repeat audit. No change in mortality or readmission rate was seen.
      CONCLUSION: Use of the Pill Pruner reduced the number of regular medications
      prescribed to older patients without affecting safety.

PMID- 25582848
TI  - The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules
      are associated with primary Sjogren's syndrome.
AB  - Primary Sjogren's syndrome (pSS) is associated with HLA-DRB1 loci, but the
      association of amino acid variations in the hypervariable region of the HLA-DR
      beta1 chain with pSS is largely unknown. In this study, we aimed to identify the
      amino acid variations within the hypervariable region of HLA-DRB1 molecule which
      are associated with the susceptibility to pSS. We sequenced the 2nd exon of the
      HLA-DRB1 locus in 52 pSS patients and 179 controls. The HLA-DRB1*0803 is the
      allele that shows the strongest association with pSS in Chinese population (OR =
      3.0, P = 2.4 * 10(-4)). Furthermore, amino acid variations within the binding
      pocket P7 and P9 are associated with the susceptibility to pSS. An interaction
      between two residues within P7, beta47 and beta67, is associated with pSS.
      Structural modeling studies demonstrated that the electrostatics of peptide
      binding pocket 9 are opposite in pSS-susceptible and -protective HLA-DRB1
      alleles. In conclusion, our results suggest that structural heterogeneity of the
      HLA-DRB1 peptide binding pocket P7 and P9 might play a role in the pathogenesis
      of pSS. 

PMID- 25582849
TI  - The role of continuous positive airway pressure in blood pressure control for
      patients with obstructive sleep apnea and hypertension: a meta-analysis of
      randomized controlled trials.
AB  - The aim of this study was to review the effect of continuous positive airway
      pressure (CPAP) on blood pressure (BP) in patients with obstructive sleep apnea
      (OSA) and hypertension. Biomedical databases were searched for randomized
      controlled trials (RCTs) comparing CPAP with control among these patients. Seven
      RCTs reporting 24-hour ambulatory BP were identified for meta-analysis. CPAP was
      associated with significant reductions in 24-hour ambulatory systolic blood
      pressure (SBP) (-2.32 mm Hg; 95% confidence interval [CI], -3.65 to -1.00) and
      diastolic blood pressure (DBP) (-1.98 mm Hg; 95% CI, -2.82 to -1.14). CPAP led to
      more significant improvement in nocturnal SBP than that in diurnal SBP. Subgroup
      analysis showed that patients with resistant hypertension or receiving
      antihypertensive drugs benefited most from CPAP. Meta-regression indicated that
      CPAP compliance, age, and baseline SBP were positively correlated with decrease
      in 24-hour DBP, but not reduction in 24-hour SBP. 

PMID- 25582850
TI  - Effect of NaFeEDTA-fortified soy sauce on zinc absorption in children.
AB  - NaFeEDTA has been applied in many foods as an iron fortificant and is used to
      prevent iron deficiency in Fe-depleted populations. In China, soy sauce is
      fortified with NaFeEDTA to control iron deficiency. However, it is unclear
      whether Fe-fortified soy sauce affects zinc absorption. To investigate whether
      NaFeEDTA-fortified soy sauce affects zinc absorption in children, sixty children
      were enrolled in this study and randomly assigned to three groups (10 male
      children and 10 female children in each group). All children received daily 3 mg
      of (67)Zn and 1.2 mg of dysprosium orally, while the children in the three groups
      were supplemented with NaFeEDTA-fortified soy sauce (6 mg Fe, NaFeEDTA group),
      FeSO4-fortified soy sauce (6 mg Fe, FeSO4 group), and no iron-fortified soy sauce
      (control group), respectively. Fecal samples were collected during the
      experimental period and analyzed for the Zn content, (67)Zn isotope ratio and
      dysprosium content. The Fe intake from NaFeEDTA-fortified and FeSO4-fortified
      groups was significantly higher than that in the control group (P < 0.0001). The
      daily total Zn intake was not significantly different among the three groups.
      There were no significant differences in fractional Zn absorption (FZA) (P =
      0.3895), dysprosium recovery (P = 0.7498) and Zn absorption (P = 0.5940) among
      the three groups. Therefore, NaFeEDTA-fortified soy sauce does not affect Zn
      bioavailability in children.

PMID- 25582851
TI  - In vitro antioxidant and inhibitory activity of water decoctions of carob tree
      (Ceratonia siliqua L.) on cholinesterases, alpha-amylase and alpha-glucosidase.
AB  - This work reports the in vitro inhibitory activity of water decoctions of leaves,
      germ flour, pulp, locust bean gum and stem bark of carob tree on alpha-amylase,
      alpha-glucosidase, acetylcholinesterase and butyrylcholinesterase. The
      antioxidant activity and the chemical characterisation of the extracts made by
      spectrophotometric assays and by high-performance liquid chromatography are also
      reported. Leaves and stem bark decoctions strongly inhibited all the enzymes
      tested, had significant antioxidant activity and the highest total phenolics
      content. The major compounds were identified as gallic acid in the leaves and
      gentisic acid in the stem bark. 

PMID- 25582852
TI  - The D0 Ig-like domain plays a central role in the stronger binding of KIR3DL2 to
      B27 free H chain dimers.
AB  - We proposed that the killer cell Ig-like receptor KIR3DL2 binding more strongly
      to HLA-B27 (B27) beta2-microglobulin free H chain (FHC) dimers than other HLA
      class I molecules regulates lymphocyte function in arthritis and infection. We
      compared the function of B27 FHC dimers with other class I H chains and
      identified contact residues in KIR3DL2. B27 FHC dimers interacted functionally
      with KIR3DL2 on NK and reporter cells more strongly than did other class I FHCs.
      Mutagenesis identified key residues in the D0 and other Ig-like domains that were
      shared and distinct from KIR3DL1 for KIR3DL2 binding to B27 and other class I
      FHCs. We modeled B27 dimer binding to KIR3DL2 and compared experimental
      mutagenesis data with computational "hot spot" predictions. Modeling predicts
      that the stronger binding of B27 dimers to KIR3DL2 is mediated by nonsymmetrical
      complementary contacts of the D0 and D1 domains with the alpha1, alpha2, and
      alpha3 domains of both B27 H chains. In contrast, the D2 domain primarily
      contacts residues in the alpha2 domain of one B27 H chain. These findings provide
      novel insights about the molecular basis of KIR3DL2 binding to B27 and other
      ligands and suggest an important role for KIR3DL2-B27 interactions in controlling
      the function of NK cells in B27(+) individuals. 

PMID- 25582853
TI  - Acquisition of activation receptor ligand by trogocytosis renders NK cells
      hyporesponsive.
AB  - Because NK cells secrete cytotoxic granules and cytokines that can destroy
      surrounding cells and help shape the subsequent immune response, they must be
      kept under tight control. Several mechanisms, at different levels, are in place
      to control NK cell function. In this study, we describe a novel mechanism
      regulating NK cell function in which NK cells acquire ligands for activating
      receptors from target cells by trogocytosis, rendering the NK cells
      hyporesponsive. In this model, murine NK cells acquire m157, the murine CMV
      encoded ligand for the Ly49H-activating receptor, from target cells both in vitro
      and in vivo. Although acquisition of m157 requires cell-to-cell contact, it does
      not require the expression of the Ly49H receptor by the NK cell. Acquired m157
      protein is expressed on the NK cell surface with a glycosylphosphatidylinisotol
      linkage and interacts with the Ly49H receptor expressed on the NK cell. This
      interaction results in blocking the Ly49H receptor that prevents the NK cells
      from recognizing m157-expressing targets and continuous engagement of the Ly49H
      activating receptor, which results in the hyporesponsiveness of the Ly49H(+) NK
      cell to stimulation through other activating receptors. Thus, NK cell acquisition
      of a ligand for an activation receptor by trogocytosis renders them
      hyporesponsive. This mechanism, by which mature NK cell function can be altered,
      has important implications in regard to how NK cells respond to tumors in
      specific microenvironments as well as the use of expanded NK cells in treating
      various malignancies. 

PMID- 25582854
TI  - Tim-1 is essential for induction and maintenance of IL-10 in regulatory B cells
      and their regulation of tissue inflammation.
AB  - T cell Ig and mucin domain (Tim)-1 identifies IL-10-producing regulatory B cells
      (Bregs). Mice on the C57BL/6 background harboring a loss-of-function Tim-1 mutant
      showed progressive loss of IL-10 production in B cells and with age developed
      severe multiorgan tissue inflammation. We demonstrate that Tim-1 expression and
      signaling in Bregs are required for optimal production of IL-10. B cells with Tim
      1 defects have impaired IL-10 production but increased proinflammatory cytokine
      production, including IL-1 and IL-6. Tim-1-deficient B cells promote Th1 and Th17
      responses but inhibit the generation of regulatory T cells (Foxp3(+) and IL-10
      producing type 1 regulatory T cells) and enhance the severity of experimental
      autoimmune encephalomyelitis. Mechanistically, Tim-1 on Bregs is required for
      apoptotic cell (AC) binding to Bregs and for AC-induced IL-10 production in
      Bregs. Treatment with ACs reduces the severity of experimental autoimmune
      encephalomyelitis in hosts with wild-type but not Tim-1-deficient Bregs.
      Collectively, these findings suggest that in addition to serving as a marker for
      identifying IL-10-producing Bregs, Tim-1 is also critical for maintaining self
      tolerance by regulating IL-10 production in Bregs. 

PMID- 25582855
TI  - Antibody-opsonized bacteria evoke an inflammatory dendritic cell phenotype and
      polyfunctional Th cells by cross-talk between TLRs and FcRs.
AB  - During secondary immune responses, Ab-opsonized bacteria are efficiently taken up
      via FcRs by dendritic cells. We now demonstrate that this process induces cross
      talk between FcRs and TLRs, which results in synergistic release of several
      inflammatory cytokines, as well as altered lipid metabolite profiles. This
      altered inflammatory profile redirects Th1 polarization toward Th17 cell
      responses. Interestingly, GM-CSF-producing Th cells were synergistically evoked
      as well, which suggests the onset of polyfunctional Th17 cells. Synergistic
      cytokine release was dependent on activation via MyD88 and ITAM signaling
      pathways through TLRs and FcRs, respectively. Cytokine regulation occurred via
      transcription-dependent mechanisms for TNF-alpha and IL-23 and
      posttranscriptional mechanisms for caspase-1-dependent release of IL-1beta.
      Furthermore, cross-talk between TLRs and FcRs was not restricted to dendritic
      cells. In conclusion, our results support that bacteria alone initiate
      fundamentally different immune responses compared with Ab-opsonized bacteria
      through the combined action of two classes of receptors and, ultimately, may
      refine new therapies for inflammatory diseases. 

PMID- 25582856
TI  - beta-arrestin1 is critical for the full activation of NLRP3 and NLRC4
      inflammasomes.
AB  - Inflammasomes are multiprotein complexes that trigger the activation of caspase-1
      and the maturation of IL-1beta, which are critical for inflammation and control
      of pathogen infection. Although the function of inflammasomes in immune response
      and disease development is well studied, the molecular mechanism by which
      inflammasomes are activated and assembled remains largely unknown. In this study,
      we found that beta-arrestin1, a key regulator of the G protein-coupled receptor
      signaling pathway, was required for nucleotide-binding domain and leucine-rich
      repeat containing (NLR) family pyrin domain-containing 3 (NLRP3) and NLR family
      CARD domain-containing protein 4 (NLRC4) inflammasome-mediated IL-1beta
      production and caspase-1 activation, but it had no effect on absent in melanoma 2
      (AIM2) inflammasome activation. Moreover, apoptosis-associated speck-like protein
      containing a CARD (ASC) pyroptosome, which is ASC aggregation mediating caspase-1
      activation, was also impaired in beta-arrestin1-deficient macrophages upon NLRP3
      or NLRC4, but not AIM2 inflammasome activation. Mechanistic study revealed that
      beta-arrestin1 specifically interacted with NLRP3 and NLRC4 and promoted their
      self-oligomerization. In vivo, in a monosodium urate crystal (MSU)-induced NLRP3
      dependent peritonitis model, MSU-induced IL-1beta production and neutrophil flux
      were significantly reduced in beta-arrestin1 knockout mice. Additionally, beta
      arrestin1 deficiency rescued the weight loss of mice upon log-phase Salmonella
      typhimurium infection, with less IL-1beta production. Taken together, our results
      indicate that beta-arrestin1 plays a critical role in the assembly and activation
      of two major canonical inflammasomes, and it may provide a new therapeutic target
      for inflammatory diseases. 

PMID- 25582857
TI  - Heme exporter FLVCR is required for T cell development and peripheral survival.
AB  - All aerobic cells and organisms must synthesize heme from the amino acid glycine
      and the tricarboxylic acid cycle intermediate succinyl CoA for incorporation into
      hemoproteins, such as the cytochromes needed for oxidative phosphorylation. Most
      studies on heme regulation have been done in erythroid cells or hepatocytes;
      however, much less is known about heme metabolism in other cell types. The feline
      leukemia virus subgroup C receptor (FLVCR) is a 12-transmembrane domain surface
      protein that exports heme from cells, and it was shown to be required for
      erythroid development. In this article, we show that deletion of Flvcr in murine
      hematopoietic precursors caused a complete block in alphabeta T cell development
      at the CD4(+)CD8(+) double-positive stage, although other lymphoid lineages were
      not affected. Moreover, FLVCR was required for the proliferation and survival of
      peripheral CD4(+) and CD8(+) T cells. These studies identify a novel and
      unexpected role for FLVCR, a major facilitator superfamily metabolite
      transporter, in T cell development and suggest that heme metabolism is
      particularly important in the T lineage. 

PMID- 25582859
TI  - Duox1-derived H2O2 modulates Cxcl8 expression and neutrophil recruitment via
      JNK/c-JUN/AP-1 signaling and chromatin modifications.
AB  - DUOX1-derived hydrogen peroxide (H2O2) and CXCL8 are two key neutrophil
      chemoattractants. H2O2 is critical at the early phase, whereas CXCL8 plays a key
      role in the late phases of recruitment, but the crosstalks between the two phases
      in vivo remain unknown. In this study using zebrafish, we report that H2O2 also
      contributes to neutrophil recruitment to injuries at the late phase as it induces
      Cxcl8 expression in vivo through a JNK/c-JUN/AP-1 signaling pathway. However, Erk
      and NF-kappaB signaling were not involved in this crosstalk. Strikingly, H2O2
      also promotes cxcl8 expression through modulation of histone 3 lysine 4
      trimethylation, histone 3 lysine 9 acetylation, and histone 3 lysine 9
      trimethylation levels at its promoter. These results explain how early H2O2
      signal regulates neutrophil recruitment at all phases, directly via Lyn oxidation
      or indirectly by modulating cxcl8 gene expression, via the activation of redox
      sensitive signaling pathways, and further point out H2O2/DUOX1 as a key drug
      target for anti-inflammatory therapies. 

PMID- 25582860
TI  - Determining the exposure factors of personal and home care products for exposure
      assessment.
AB  - An accurate understanding of the usage patterns of consumer products is important
      for realistic exposure assessment. Since such patterns differ by country, a
      Korean national database for exposure factors is needed. We determined the
      exposure factors of 10 consumer products (face cleanser, toothpaste, shampoo,
      hair conditioner, body wash, dish and laundry detergents, fabric deodorizer,
      antistatic spray, and shoe polish. Field survey staff visited homes and collected
      product use information by questionnaire. In total, 816 men and 2517 women aged
      15 years and older from 2500 households completed the questionnaire. Field
      technicians also re-visited 85 households to investigate the circumstances of use
      and the reliability of the questionnaire data. Greater than 97% of the sampled
      population reported use of toothpaste and shampoo. Hair conditioner, body wash,
      and face cleanser were used by ~60% of the population and by specific age groups
      and genders. The amount of consumer products used was comparable between that
      reported in the questionnaire and that measured directly during house visits, and
      the ratios of usage amounts ranged from 0.75 to 1.69. The exposure factor data
      obtained from this study could be useful for regulatory agencies when setting
      safety guidelines for product use. 

PMID- 25582858
TI  - Defective selection of thymic regulatory T cells accompanies autoimmunity and
      pulmonary infiltrates in Tcra-deficient mice double transgenic for human
      La/Sjogren's syndrome-B and human La-specific TCR.
AB  - A human La/Sjogren's syndrome-B (hLa)-specific TCR/hLa neo-self-Ag double
      transgenic (Tg) mouse model was developed and used to investigate cellular
      tolerance and autoimmunity to the ubiquitous RNA-binding La Ag often targeted in
      systemic lupus erythematosus and Sjogren's syndrome. Extensive thymic clonal
      deletion of CD4(+) T cells occurred in H-2(k/k) double-Tg mice presenting high
      levels of the I-E(k)-restricted hLa T cell epitope. In contrast, deletion was
      less extensive in H-2(k/b) double-Tg mice presenting lower levels of the epitope,
      and some surviving thymocytes were positively selected as thymic regulatory T
      cells (tTreg). These mice remained serologically tolerant to hLa and healthy. H
      2(k/b) double-Tg mice deficient of all endogenous Tcra genes, a deficiency known
      to impair Treg development and function, produced IgG anti-hLa autoantibodies and
      displayed defective tTreg development. These autoimmune mice had interstitial
      lung disease characterized by lymphocytic aggregates containing Tg T cells with
      an activated, effector memory phenotype. Salivary gland infiltrates were notably
      absent. Thus, expression of nuclear hLa Ag induces thymic clonal deletion and
      tTreg selection, and lymphocytic infiltration of the lung is a consequence of La
      specific CD4(+) T cell autoimmunity. 

PMID- 25582861
TI  - Self-reported preparedness of New Zealand acute care providers to mass
      emergencies before the Canterbury Earthquakes: a national survey.
AB  - INTRODUCTION: Disasters occur more frequently. Acute care providers are the first
      to respond to mass emergencies from the healthcare sector. The preparedness of
      acute care providers in New Zealand to respond to mass emergencies has not been
      previously studied. OBJECTIVE: To assess the self-reported training and
      experience of New Zealand acute care providers to respond to mass emergencies and
      the factors associated with strong preparedness. METHODS: A cross-sectional
      national survey of 1500 acute care providers in New Zealand carried out between
      2009 and 2010. The survey assessed experience, training and self-reported
      preparedness. It also determined the factors associated with strong perceived
      preparedness. RESULTS: The response rate to this survey was 60.7%. Nurses had a
      higher response rate than doctors or paramedics. Only 29.2% of acute care
      providers reported responding to a previous mass emergency event. There were
      53.5% of acute care providers who reported having formal training in how to deal
      with mass emergencies, whereas 58.1% of participants reported that they were
      aware of their role during a healthcare mass emergency response. The factors
      associated with self-reported strong preparedness to deal with mass emergencies
      included: being a paramedic, previous training, participation in a drill,
      willingness to report to work during an infection or man-made emergency, ability
      to triage and general awareness of the role during a mass emergency. CONCLUSION:
      Almost half of New Zealand acute healthcare providers have no training in dealing
      with mass emergency events. Training and general awareness of the role during a
      mass emergency response were the main factors associated with strong self
      reported preparedness of acute care providers. The apparent efficacy of training
      allied to lack of availability means that it should be a national priority.

PMID- 25582862
TI  - Conventional US, elastography, and contrast enhanced US features of papillary
      thyroid microcarcinoma predict central compartment lymph node metastases.
AB  - Lymph node metastases at the time of diagnosis have a major impact on both
      therapeutic strategy and tumor recurrence for patients with papillary thyroid
      microcarcinoma (PTMC). Our objective was to evaluate the usefulness of PTMC
      characteristics on ultrasonography for predicting central compartment lymph node
      metastases (CCLNM) of PTMC. One hundred twenty seven patients who underwent
      surgery for PTMC were enrolled in this study. The relationship between the CCLNM
      and the characteristics on conventional US, elastographic, and contrast enhanced
      ultrasound (CEUS) were investigated. Univariate analysis indicated that PTMCs
      with CCLNM were more often nodule irregular shape, microcalcifications,
      hyperenhancing or isoenhancing parametric maps, and peak index >=1 at
      preoperative US and CEUS than those without CCLNM (P< 0.01, 0.05, 0.01 and 0.05
      respectively). Multivariate analysis showed that microcalcification (OR:2.378,
      95% CI: 1.096-5.158) and hyperenhancement or isoenhancement (OR:2.8, 95% CI:
      1.287-6.094) were predictive for the presence of CCLNM. Elastography score was
      not significantly different between the groups. Our study indicated that
      preoperative thyroid nodule characteristics on conventional US and CEUS may serve
      as a useful tool to predict central compartment lymph node metastases in PTMC. 

PMID- 25582863
TI  - Managing and eradicating wildlife tuberculosis in New Zealand.
AB  - Tuberculosis (TB) due to Mycobacterium bovis infection was first identified in
      brushtail possums (Trichosurus vulpecula) in New Zealand in the late 1960s. Since
      the early 1970s, possums in New Zealand have been controlled as part of an
      ongoing strategy to manage the disease in livestock. The TB management authority
      (TBfree New Zealand) currently implements three strategic choices for disease
      related possum control: firstly TB eradication in areas selected for eradication
      of the disease from livestock and wildlife, secondly Free Area Protection in
      areas in which possums are maintained at low densities, normally along a Vector
      Risk Area (VRA) boundary, and thirdly Infected Herd Suppression, which includes
      the remaining parts of VRA where possums are targeted to minimise the infection
      risk to livestock. Management is primarily through a range of lethal control
      options. The frequency and intensity of control is driven by a requirement to
      reduce populations to very low levels (usually to a trap-catch index below 2%),
      then to hold them at or below this level for 5-10 years to ensure disease
      eradication.Lethal possum control is implemented using aerial- and ground-based
      applications, under various regulatory and operational constraints. Extensive
      research has been undertaken aimed at improving the efficacy and efficiency of
      control. Aerial applications use sodium fluoroacetate (1080) bait for controlling
      possums over extensive and rugged areas of forest that are difficult to access by
      foot. Ground-based control uses a range of toxins (primarily, a potassium cyanide
      based product) and traps. In the last 5 years there has been a shift from simple
      possum population control to the collection of spatial data on possum
      presence/absence and relative density, using simple possum detection devices
      using global positioning system-supported data collection tools, with recovery of
      possum carcasses for diagnostic necropsy. Such data provide information
      subsequently used in predictive epidemiological models to generate a probability
      of TB freedom.The strategies for managing TB in New Zealand wildlife now operate
      on four major principles: firstly a target threshold for possum population
      reduction is defined and set, secondly an objective methodology is applied for
      assessing whether target reductions have been achieved, thirdly effective control
      tools for achieving possum population reductions are used, and fourthly the
      necessary legislative support is in place to ensure compliance. TBfree New
      Zealand's possum control programme meets these requirements, providing an
      excellent example of an effective pest and disease control programme. 

PMID- 25582866
TI  - Ultrasensitive and ultraselective impedimetric detection of Cr(VI) using crown
      ethers as high-affinity targeting receptors.
AB  - Detection of Cr(VI) by electrochemical methods generally focuses on noble-metal
      modified electrodes in strong acid solution using voltammetric techniques. In
      this work, we report a new strategy to detect Cr(VI) as HCrO4(-) at pH 5.0 in
      drinking water using electrochemical impedance spectroscopy. The strategy is
      based on the high-affinity and specific binding of crown ethers (i.e., azacrown)
      to HCrO4(-), which forms sandwich complexes between them via hydrogen bonds and
      moiety interactions with K(+) captured by azacrown on its self-assembled Au
      electrode surface. This then blocks the access of redox probes (Fe(CN)6(3-/4-))
      to the self-assembled Au electrode, further resulting in an increase in the
      electron transfer resistance. This method offers a detection limit of 0.0014 ppb
      Cr(VI) with a sensitivity of 4575.28 kOmega [log c (ppb)](-1) over the linear
      range of 1-100 ppb (R(2) = 0.994) at pH 5.0. In addition, the azacrown self
      assembled Au electrode has good selectivity for Cr(VI) with good stability and
      low interferences. This approach can be performed on spiked Cr(VI) as well as
      real samples. To the best of our knowledge, this is the first example of
      electrochemical impedimetric sensing that allows ultrasensitive and
      ultraselective detection of Cr(VI). 

PMID- 25582867
TI  - Combined hypoxia and sodium nitrite pretreatment for cardiomyocyte protection in
      vitro.
AB  - Methods that increase cardiomyocyte survival upon exposure to ischemia, hypoxia
      and reoxygenation injuries are required to improve the efficacy of cardiac cell
      therapy and enhance the viability and function of engineered tissues. We
      investigated the effect of combined hypoxia/NaNO2 pretreatment on rat neonatal
      cardiomyocyte (CM), cardiac fibroblast, and human embryonic stem cell-derived CM
      (hESC-CM) survival upon exposure to hypoxia/reoxygenation (H/R) injury in vitro.
      Cells were pretreated with and without hypoxia and/or various concentrations of
      NaNO2 for 20 min, then incubated for 2 h under hypoxic conditions, followed by 2
      h in normoxia. The control cells were maintained under normoxia for 4 h.
      Pretreatment with either hypoxia or NaNO2 significantly increased CM viability
      but had no effect on cardiac fibroblast viability. Combined hypoxia/NaNO2
      pretreatment significantly increased CM viability but significantly decreased
      cardiac fibroblast viability. In rat neonatal CMs, cell death, as determined by
      lactate dehydrogenase (LDH) activity, was significantly reduced with
      hypoxia/NaNO2 pretreatment; and in hESC-CMs, hypoxia/NaNO2 pretreatment increased
      the BCL-2/BAX gene expression ratio, suggesting that hypoxia/NaNO2 pretreatment
      promotes cell viability by downregulating apoptosis. Additionally, we found a
      correlation between the prosurvival effect of hypoxia/NaNO2 pretreatment and the
      myoglobin content of the cells by comparing neonatal rat ventricular and atrial
      CMs, which express high and low myoglobin respectively. Functionally,
      hypoxia/NaNO2 pretreatment significantly improved the excitation threshold upon
      H/R injury to the level observed for uninjured cells, whereas pretreatment did
      not affect the maximum capture rate. Hence, hypoxia/NaNO2 pretreatment may serve
      as a strategy to increase CM survival in cardiac regenerative therapy
      applications and tissue engineering.

PMID- 25582868
TI  - Resource availability as a proxy for terminal investment in a beetle.
AB  - Terminal investment hypothesis is a longstanding theoretical idea that organisms
      should increase their reproductive effort as their prospects for survival and
      reproduction decline. However, numerous attempts to test the terminal investment
      in reproduction have yielded contradictory results. This study reports an
      experimental confirmation of the terminal investment hypothesis. It was predicted
      that immune-challenged yellow mealworm beetles (Tenebrio molitor) are more likely
      to follow terminal investment strategy when their food resources are limited. Our
      results suggest the key role of food resources while making decisions to follow a
      terminal investment strategy. We found that male individuals invested in their
      sexual attractiveness at the expense of immune response and survival when food
      was not available. In contrast, the beetles did not decrease their lifespan and
      did not invest in the attractiveness of their sex odours under conditions of food
      ad libitum. Our results show the importance of food availability and quality in
      understanding the evolution of reproductive strategies. 

PMID- 25582869
TI  - Is there a trade-off between glucosinolate-based organic and inorganic defences
      in a metal hyperaccumulator in the field?
AB  - Several plant species are able to not only tolerate but also hyperaccumulate
      heavy metals in their aboveground tissues. Thus, in addition to secondary
      metabolites acting as organic defences, metal hyperaccumulators possess an
      elemental defence that can act as protection against antagonists. Whereas several
      laboratory studies have determined potential relationships or trade-offs between
      organic and inorganic defences, little is known about whether these traits are
      interconnected in the field and which factors determine the compositions of
      organic defences and elements of leaf tissues most. To target these questions, we
      collected young leaves of Arabidopsis halleri, a Brassicaceae capable of
      hyperaccumulating Cd and Zn, as well as soil samples in the field from 16
      populations. We detected wide variation in the composition of glucosinolates-the
      characteristic secondary metabolites of this plant family-among plants, with two
      distinct chemotypes occurring. Distance-based redundancy analyses revealed that
      variation in glucosinolate composition was determined mainly by population
      affiliation and to a lesser degree by geographic distance. Likewise, elemental
      composition of the leaves was mainly influenced by the location at which samples
      were collected. Therefore, the particular abiotic and biotic conditions and
      potential genetic relatedness at a particular locality affect the plant tissue
      chemistry. A slight indication of a trade-off between glucosinolate-based organic
      and inorganic defences was found, but only in the less abundant chemotype. A
      large variation in defence composition and potential joint effects of different
      defences may be highly adaptive ways of protecting against a wide arsenal of
      biotic antagonists. 

PMID- 25582870
TI  - The Tennessee study: factors affecting treatment outcome and healing time
      following nonsurgical root canal treatment.
AB  - AIM: To determine factors that may influence treatment outcome and healing time
      following root canal treatment. METHODOLOGY: Root filled and restored teeth by
      pre-doctoral students were included in this study. Teeth/roots were followed-up
      regularly, and treatment outcome was evaluated at every follow-up appointment
      (healed, healing, uncertain or unsatisfactory). Host (age, immune condition,
      pulp/periapical diagnosis, tooth/root type, location and anatomy) and treatment
      factors (master apical file size, apical extension, voids and density of root
      filling) were recorded from patient dental records. Univariate, bivariate and
      multivariate analyses were performed to determine the impact of the factors on
      treatment outcomes and healing times. RESULTS: A total of 422 roots from 291
      teeth met the inclusion criteria with a mean follow-up period of 2 years. The
      preoperative pulp condition, procedural errors during treatment, apical extension
      and density of root fillings significantly affected the treatment outcome. The
      average time required for a periapical lesion to heal was 11.78 months. The
      healing time increased in patients with compromised healing, patients older than
      40 years, roots with Weine type II root canal systems, root canal systems
      prepared to a master apical file size <35, and roots with overextended fillings
      (P < 0.1). CONCLUSION: Multiple host and treatment factors affected the healing
      time and outcome of root canal treatment. Follow-up protocols should consider
      these factors before concluding the treatment outcome: patient's age, immune
      condition, as well as roots with overextended fillings, root canal systems with
      smaller apical preparations (size <35) or roots with complex canal systems.
      Intervention may be recommended if the treatment quality was inadequate or if
      patients became symptomatic.

PMID- 25582871
TI  - Latent autoimmune diabetes in adults: are we paying sufficient attention?

PMID- 25582872
TI  - Role of 99mTc-HYNIC-Tyr3-octreotide scintigraphy in neuroendocrine tumors based
      on localization of the primary tumor.
AB  - BACKGROUND: The aim of our work was to determine the accuracy of 99mTc-HYNIC Tyr3
      octreotide scintigraphy (TcOS) in detecting active disease in neuroendocrine
      tumors (NETs) based on embryological origin of the primary tumor (foregut, midgut
      or hindgut). METHODS: We analyzed retrospectively 45 studies (12 staging, 26
      suspicion of recurrence, and 7 treatment response) belonging to 33 patients with
      histological confirmation of NETs. Whole body scan and a SPECT-CT were acquired 4
      hours post-injection of 740 MBq of 99mTc-HYNIC Tyr3 octreotide. The studies were
      divided into 3 groups based on the embryological origin of primary tumor (foregut
      [group 1], midgut [group 2] and hindgut [group 3]). The accuracy of TcOS in each
      group was assessed, included chi-square analyses. The final diagnosis was
      established by histopathology or clinical/radiological follow-up greater than 6
      months. RESULTS: The localization of the primary tumor per patient revealed that
      58% were from the foregut, 30% from the midgut and 12% from the hindgut. In study
      based analysis (45 studies), TcOS showed an overall sensitivity, specificity and
      accuracy of 95%, 92% and 93% respectively. The accuracy per studies for the
      groups 1, 2 and 3 were: 100%, 92% and 66% respectively, demonstrating a better
      detection of active disease in primary tumors from foregut and midgut compared to
      hindgut (P=0.02). CONCLUSIONS: The accuracy of TcOS in the assessment of NETs
      seems to be better in tumors with foregut and midgut origin, showing a possible
      relationship between the embryological origin of NETs and detection of active
      disease by TcOS.

PMID- 25582873
TI  - Return to play after nonoperative management for a severe type III
      acromioclavicular separation in the throwing shoulder of a collegiate pitcher.
AB  - BACKGROUND: Treatment of type III acromioclavicular (AC) separations is
      controversial, especially in the dominant shoulder of a high-level throwing
      athlete. This case report describes the return to play after nonoperative
      management of a collegiate baseball pitcher with a severe type III AC separation
      in his throwing shoulder. HYPOTHESIS/PURPOSE: Case report of return to play with
      nonoperative management of a type III AC separation in the throwing shoulder of a
      collegiate pitcher. STUDY DESIGN: A case report of a single patient. METHODS:
      Prospective data were recorded in the case of a collegiate pitcher who suffered
      an acute injury to the dominant shoulder, resulting in a severe type III AC
      separation. He was initially treated with a figure-of-8 brace and a sling.
      Postinjury, strengthening of the wrist, hand, and elbow began at 31/2 weeks, and
      shoulder range of motion (ROM) and a periscapular strengthening program began at
      6 weeks. At 2 months postinjury, a deformity was still present, but the athlete
      was pain free, with full shoulder ROM and strength without tenderness at the AC
      joint. Formal physical therapy was initiated to include an accelerated interval
      throwing program. RESULTS: At 12 weeks postinjury, the athlete was pitching
      asymptomatically, and gradually returned to regular play. At 6 months and now
      through 24 months postinjury, the athlete reported full strength, full ROM, and
      return to his previous level of throwing and velocity without complication. He
      volunteered that he was 100% satisfied with the result, and feels he is the same
      pitcher as, if not stronger than, prior to this injury. CONCLUSIONS: This case
      demonstrates a collegiate baseball pitcher who returned to his preinjury level of
      pitching with nonoperative treatment of a severe type III AC separation.

PMID- 25582874
TI  - Peripheral neuropathy and parkinsonism: a large clinical and pathogenic spectrum.
AB  - Peripheral neuropathy (PN) has been reported in idiopathic and hereditary forms
      of parkinsonism, but the pathogenic mechanisms are unclear and likely
      heterogeneous. Levodopa-induced vitamin B12 deficiency has been discussed as a
      causal factor of PN in idiopathic Parkinson's disease, but peripheral nervous
      system involvement might also be a consequence of the underlying
      neurodegenerative process. Occurrence of PN with parkinsonism has been associated
      with a panel of mitochondrial cytopathies, more frequently related to a nuclear
      gene defect and mainly polymerase gamma (POLG1) gene. Parkin (PARK2) gene
      mutations are responsible for juvenile parkinsonism, and possible peripheral
      nervous system involvement has been reported. Rarely, an association of
      parkinsonism with PN may be encountered in other neurodegenerative diseases such
      as fragile X-associated tremor and ataxia syndrome related to premutation CGG
      repeat expansion in the fragile X mental retardation (FMR1) gene, Machado-Joseph
      disease related to an abnormal CAG repeat expansion in ataxin-3 (ATXN3) gene,
      Kufor-Rakeb syndrome caused by mutations in ATP13A2 gene, or in hereditary
      systemic disorders such as Gaucher disease due to mutations in the beta
      glucocerebrosidase (GBA) gene and Chediak-Higashi syndrome due to LYST gene
      mutations. This article reviews conditions in which PN may coexist with
      parkinsonism. 

PMID- 25582875
TI  - Circumferential pulmonary vein isolation as index procedure for persistent atrial
      fibrillation: a comparison between radiofrequency catheter ablation and second
      generation cryoballoon ablation.
AB  - AIMS: To assess the 1 year efficacy of pulmonary vein isolation (PVI) as index
      procedure for persistent atrial fibrillation (PersAF) comparing conventional
      radiofrequency irrigated-tip catheter ablation (RFCA) using contact-force
      technology and ablation using the second-generation cryoballoon (CB-AdvA).
      METHODS AND RESULTS: One hundred consecutive patients (74 male, 74%; mean age
      62.4 +/- 9.6 years) with drug-refractory PersAF undergoing PVI using RFCA and CB
      AdvA were enrolled. Follow-up was based on outpatient clinic visits including
      Holter-electrocardiograms. Recurrence of atrial tachyarrhythmias (ATas) was
      defined as a symptomatic or documented episode >30 s. Among 100 patients, 50
      underwent RFCA whereas 50 CB-AdvA. Mean procedure and fluoroscopy times were 90.5
      +/- 41.7 vs. 140.2 +/- 46.9 min and 14.5 +/- 6.6 vs. 19.8 +/- 6.8 min in the CB
      Adv and in the RFCA group, respectively (P < 0.01). At 1 year follow-up, after a
      3 months blanking period (BP), freedom from ATas off-drugs after a single
      procedure was 60% (28/50 patients) in the CB-Adv and 56% (27/50 patients) in the
      RFCA group (P = 0.71). Multivariate analysis demonstrated that PersAF duration (P
      = 0.01) and relapses during BP (P = 0.02) were independent predictors of ATa
      recurrences following the index procedure. CONCLUSION: Freedom from ATas
      following PersAF ablation with RFCA and CB-Adv is comparable at 1 year follow-up
      after a single procedure. Ablation with the CB-Adv is associated with shorter
      procedure time and radiation exposure as compared with RFCA. Atrial
      tachyarrhythmias occurrence during BP and longer time of PersAF seem to be
      significant predictors of arrhythmia recurrences after the index procedure.

PMID- 25582865
TI  - Climate niche differentiation between two passerines despite ongoing gene flow.
AB  - Niche evolution underpins the generation and maintenance of biological diversity,
      but niche conservatism, in which niches remain little changed over time in
      closely related taxa, and the role of ecology in niche evolution are continually
      debated. To test whether climate niches are conserved in two closely related
      passerines in East Asia - the vinous-throated (Paradoxornis webbianus) and ashy
      throated (P. alphonsianus) parrotbills - we established their potential
      allopatric and sympatric regions using ecological niche models and compared
      differences in their climate niches using niche overlap indices in background
      tests and multivariate statistical analyses. We also used polymorphism data on 44
      nuclear genes to infer their divergence demography. We found that these two
      parrotbills occupy different climate niches, in both their allopatric and
      potential sympatric regions. Because the potential sympatric region is the area
      predicted to be suitable for both parrotbills based on the ecological niche
      models, it can serve as a natural common garden. Therefore, their observed niche
      differences in this potential sympatry were not simply rendered by phenotypic
      plasticity and probably had a genetic basis. Our genetic analyses revealed that
      the two parrotbills are not evolutionarily independent for the most recent part
      of their divergence history. The two parrotbills diverged c. 856,000 years ago
      and have had substantial gene flow since a presumed secondary contact c. 290,000
      years ago. This study provides an empirical case demonstrating that climate
      niches may not be homogenized in nascent species in spite of substantial, ongoing
      gene flow, which in turn suggests a role for ecology in promoting and maintaining
      diversification among incipient species.

PMID- 25582877
TI  - Correction.
AB  - [This corrects the article DOI: 10.1136/bmjresp-2014-000022.]. 

PMID- 25582876
TI  - Intracranial self-stimulation reward thresholds during morphine withdrawal in
      rats bred for high (HiS) and low (LoS) saccharin intake.
AB  - RATIONALE: Sweet preference is a marker of vulnerability to substance use
      disorders, and rats selectively bred for high (HiS) vs. low saccharin (LoS)
      intake display potentiated drug-seeking behaviors. Recent work indicated that LoS
      rats were more responsive to the negative effects of drugs in several assays.
      OBJECTIVE: The current study used the intracranial self-stimulation (ICSS)
      procedure to investigate the anhedonic component of morphine withdrawal in male
      HiS and LoS rats. METHODS: Rats were administered morphine (10mg/kg) or saline
      for 8 days. To evaluate withdrawal effects, reward thresholds were measured 24
      and 28h following the 8th morphine injection (spontaneous withdrawal) and again
      for 4 days following daily acute morphine and naloxone (1mg/kg) administration
      (precipitated withdrawal). RESULTS: 24h following the final morphine injection,
      reward thresholds in LoS rats were significantly elevated compared to reward
      thresholds in LoS controls, indicating spontaneous withdrawal. This effect was
      not observed in HiS rats. LoS rats also showed greater elevations of reward
      thresholds on several days during naloxone-precipitated withdrawal compared to
      their HiS counterparts. CONCLUSIONS: LoS rats were more sensitive to morphine
      withdrawal-mediated elevations in ICSS thresholds than HiS rats. While these
      differences were generally modest, our data suggest that severity of the negative
      affective component of opiate withdrawal may be influenced by genotypes related
      to addiction vulnerability.

PMID- 25582878
TI  - Duration of active psychosis and first-episode psychosis negative symptoms.
AB  - AIM: Duration of untreated psychosis (DUP) has been associated with negative
      symptoms in several studies; however, longitudinal findings have been
      inconsistent. No previous study has accounted for active psychosis after
      presentation, although this could impact on outcomes in a manner similar to DUP.
      METHODS: We measured Scale for the Assessment of Positive Symptoms at frequent
      intervals during the 12 months after initial presentation to determine the active
      psychosis duration for 230 individuals with first-episode psychosis. This
      duration was added to DUP prior to presentation to create a new variable,
      duration of active psychosis (DAP). Negative symptoms were divided into
      expressivity and motivation/pleasure domains as measured by Scale for the
      Assessment of Negative Symptoms (SANS). The relationship of DUP and DAP with
      negative symptoms at 24-month follow up was determined and confounders controlled
      for using regression analysis. RESULTS: When DUP and DAP were compared as binary
      variables with long and short groups, 25.2% of individuals had differing category
      membership. DAP had a significant uncorrected association with both expressivity
      domain and motivation/pleasure domains at 24 months; however, relationship with
      DUP was not significant. DAP remained a significant predictor of 24-month
      expressivity domain after controlling for potential confounders. CONCLUSIONS:
      Active psychosis after presentation is substantial, which is a limitation of DUP
      studies if active psychosis is considered as the key factor within DUP. DAP is a
      better predictor of negative symptoms than DUP at 2-year follow up, which
      suggests this concept requires further research.

PMID- 25582880
TI  - Implementation of a trauma system in Norway: a national survey.
AB  - BACKGROUND: Trauma systems have improved outcomes for injured patients, but might
      be challenging to implement. We assessed the implementation of a trauma system in
      Norway after recommendations for a national trauma system were published in 2007,
      with a focus on elements in acute care hospitals. METHODS: All hospitals in
      Norway, except for the four regional trauma centres, admitting injured patients
      at the time of the study were included in a telephone survey. The questionnaire
      was administered during May 2013 by the regional trauma coordinators who
      interviewed the local trauma coordinator and/or the local doctor responsible for
      trauma care in all the acute care hospitals. The main categories were
      availability of the trauma team and team training, written procedures,
      preparedness and training of personnel. The compliance to a set of 17 predefined
      trauma system criteria was evaluated at each institution. RESULTS: Of the 35
      acute care hospitals in Norway admitting trauma patients at the time of the
      survey, all were included. The median number of fulfilled criteria was 14. Major
      deficiencies were found in fulfilling competence criteria, maintaining a local
      trauma registry, and trauma audits. The number of fulfilled criteria correlated
      strongly with the size of the hospital and the frequency of trauma team
      activation. CONCLUSIONS: Shortcomings in requirements for lower-level trauma care
      hospitals correlate to hospital size and frequency with which the trauma team is
      activated. In order to fulfill the minimum requirements, smaller hospitals should
      receive more attention.

PMID- 25582879
TI  - Effect of continuous positive airway pressure on insulin growth factor-1 in
      patients with obstructive sleep apnea: a meta-analysis.
AB  - OBJECTIVE: Obstructive sleep apnea (OSA) has been recognized as being associated
      with low level of insulin growth factor-1 (IGF-1). However, the impact of OSA
      treatment using continuous positive airway pressure (CPAP) on IGF-1 remains
      controversial. We performed a meta-analysis to determine whether effective CPAP
      therapy could increase IGF-1 levels. DESIGN: Two reviewers independently searched
      PubMed, Cochrane library, Embase and Web of Science before September 2014.
      Information on characteristics of subjects, study design and pre- and post-CPAP
      treatment of serum IGF-1 was extracted for analysis. Standardized mean difference
      (SMD) was used to analyze the summary estimates for CPAP therapy. RESULTS: Six
      articles with 168 patients were included in this meta-analysis, including five
      observational studies and one randomized controlled study. The meta-analysis
      showed that CPAP was associated with a statistically significant increase in IGF
      1 in OSA patients (SMD=-0.436, 95% confidence interval=-0.653 to -0.218,
      P=0.000). CONCLUSIONS: This meta-analysis suggested that CPAP therapy was
      associated with an increase in IGF-1 in patients with OSA. Further large-scale,
      well-designed interventional investigations are needed to clarify this issue.

PMID- 25582882
TI  - Highly time-resolved imaging of combustion and pyrolysis product concentrations
      in solid fuel combustion: NO formation in a burning cigarette.
AB  - The highly dynamic, heterogeneous combustion process within a burning cigarette
      was investigated by a miniaturized extractive sampling probe (microprobe) coupled
      to photoionization mass spectrometry using soft laser single photon ionization
      (SPI) for online real-time detection of molecular ions of combustion and
      pyrolysis products. Research cigarettes smoked by a smoking machine are used as a
      reproducible model system for solid-state biomass combustion, which up to now is
      not addressable by current combustion-diagnostic tools. By combining repetitively
      recorded online measurement sequences from different sampling locations in an
      imaging approach, highly time- and space-resolved quantitative distribution maps
      of, e.g., nitrogen monoxide, benzene, and oxygen concentrations were obtained at
      a near microscopic level. The obtained quantitative distribution maps represent a
      time-resolved, movie-like imaging of the respective compound's formation and
      destruction zones in the various combustion and pyrolysis regions of a cigarette
      during puffing. Furthermore, spatially resolved kinetic data were ascertainable.
      The here demonstrated methodology can also be applied to various heterogenic
      combustion/pyrolysis or reaction model systems, such as fossil- or biomass-fuel
      pellet combustion or to a positional resolved analysis of heterogenic catalytic
      reactions. 

PMID- 25582881
TI  - Cardiovascular disease risk burden in primary Sjogren's syndrome: results of a
      population-based multicentre cohort study.
AB  - OBJECTIVE: Systemic autoimmune diseases, in particular systemic lupus
      erythematosus and rheumatoid arthritis, are characterized by a high risk of
      premature cardiovascular (CV) events. Disease-related characteristics and
      traditional CV disease risk factors may contribute to atherosclerotic damage.
      However, there are limited data on the risk of overt CV events in primary
      Sjogren's syndrome (pSS). METHODS: We retrospectively analysed a cohort of
      patients with 1343 pSS. Disease-related clinical and laboratory data, traditional
      CV disease risk factors and overt CV events were recorded. Prevalence of
      traditional CV disease risk factors and of major CV events was compared between a
      subgroup of 788 female patients with pSS aged from 35 to 74 years and 4774 age
      matched healthy women. RESULTS: Hypertension and hypercholesterolaemia were more
      prevalent, whereas smoking, obesity and diabetes mellitus were less prevalent, in
      women with pSS than in control subjects. Cerebrovascular events (2.5% vs. 1.4%, P
      = 0.005) and myocardial infarction (MI) (1.0% vs. 0.4%, P = 0.002) were more
      common in patients with pSS. In the whole population, central nervous system
      involvement (odds ratio (OR) 5.6, 95% confidence interval (CI) 1.35-23.7, P =
      0.02) and use of immunosuppressive therapy (OR 1.9, 95% CI 1.04-3.70, P = 0.04)
      were associated with a higher risk of CV events. Patients with leucopenia had a
      higher risk of angina (P = 0.01). CONCLUSIONS: pSS is associated with an
      increased risk of cerebrovascular events and MI. Disease-related clinical and
      immunological markers may have a role in promoting CV events.

PMID- 25582883
TI  - Core decompression treatment of early-stage osteonecrosis of femoral head
      resulted from venous stasis or artery blood supply insufficiency.
AB  - BACKGROUND: The objective of this study was to explore the therapeutic effect of
      core decompression on different hemodynamics changes associated with
      osteonecrosis of the femoral head (ONFH). METHODS: A total of 67 patients with 76
      hips suffering from ONFH (Arco stage I-IIC) received core decompression surgical
      procedure. Radiographic, magnetic resonance imaging, and digital subtraction
      angiography examinations were performed before operation. Radiographic and
      magnetic resonance imaging follow-ups were also performed after 12, 24, and 60 mo
      of operation. Clinical follow-ups were performed using the Harris Hip Score (HHS)
      for an average period of 5 y postoperation. RESULTS: The mean follow-up time
      ranged from 2-8 y with an average of 5 y. Two hips were lost during follow-up.
      Successful clinical efficacy (HHS >=80) was achieved in 91.9% (68/74) of the
      hips. Six hips had conversion to total hip arthroplasty (THA), one hip had venous
      stasis, and five hips had both vein stasis and artery blood supply insufficiency.
      The mean HHS for the patients who did not have conversion to THA improved from 65
      +/- 3.5 to 89 +/- 3.6 (mean +/- standard deviation). Twenty-six stage I hips
      (100%), 22 of 23 stage IIA hips (95.7%), 13 of 15 stage IIB hips (86.7%), and 8
      of 10 stage IIC hips (80%) had successful outcomes with no surgical
      complications. Kaplan-Meier survival analysis showed that 8-y survival rate was
      significantly different between stage I and stage IIC (THA as an end point; P <
      0.001). CONCLUSIONS: In patients with early-stage ONFH resulted from only venous
      stasis, core decompression led to a significant improvement in HHS and 8-y
      survival rate. However, the long-term efficacy for ONFH associated with artery
      blood supply insufficiency was not encouraging. Therefore, preoperative digital
      subtraction angiography is necessary before performing core decompression.

PMID- 25582884
TI  - Clinicopathologic study of intestinal spirochetosis in Japan with special
      reference to human immunodeficiency virus infection status and species types:
      analysis of 5265 consecutive colorectal biopsies.
AB  - BACKGROUND: Previous studies reported that the incidence of intestinal
      spirochetosis was high in homosexual men, especially those with Human
      Immunodeficiency Virus infection. The aim of the present study was to clarify the
      clinicopathological features of intestinal spirochetosis in Japan with special
      reference to Human Immunodeficiency Virus infection status and species types.
      METHODS: A pathology database search for intestinal spirochetosis was performed
      at Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital
      between January 2008 and October 2011, and included 5265 consecutive colorectal
      biopsies from 4254 patients. After patient identification, a retrospective review
      of endoscopic records and clinical information was performed. All pathology
      slides were reviewed by two pathologists. The length of the spirochetes was
      measured using a digital microscope. Causative species were identified by
      polymerase chain reaction. RESULTS: Intestinal spirochetosis was diagnosed in 3
      out of 55 Human Immunodeficiency Virus-positive patients (5.5%). The mean length
      of intestinal spirochetes was 8.5 MUm (range 7-11). Brachyspira pilosicoli was
      detected by polymerase chain reaction in all 3 patients. Intestinal spirochetosis
      was also diagnosed in 73 out of 4199 Human Immunodeficiency Virus-negative
      patients (1.7%). The mean length of intestinal spirochetes was 3.5 MUm (range 2
      8). The species of intestinal spirochetosis was identified by polymerase chain
      reaction in 31 Human Immunodeficiency Virus-negative patients. Brachyspira
      aalborgi was detected in 24 cases (78%) and Brachyspira pilosicoli in 6 cases
      (19%). Both Brachyspira aalborgi and Brachyspira pilosicoli were detected in only
      one Human Immunodeficiency Virus-negative patient (3%). The mean length of
      Brachyspira aalborgi was 3.8 MUm, while that of Brachyspira pilosicoli was 5.5
      MUm. The length of Brachyspira pilosicoli was significantly longer than that of
      Brachyspira aalborgi (p < 0.01). The lengths of intestinal spirochetes were
      significantly longer in Human Immunodeficiency Virus-positive patients than in
      Human Immunodeficiency Virus-negative patients (p < 0.05). CONCLUSIONS: The
      incidence of intestinal spirochetosis was slightly higher in Human
      Immunodeficiency Virus-positive patients than in Human Immunodeficiency Virus
      negative patients. However, no relationship was found between the Human
      Immunodeficiency Virus status and intestinal spirochetosis in Japan. Brachyspira
      pilosicoli infection may be more common in Human Immunodeficiency Virus-positive
      patients with intestinal spirochetosis than in Human Immunodeficiency Virus
      negative patients with intestinal spirochetosis.

PMID- 25582885
TI  - The general stress response in Alphaproteobacteria.
AB  - The general stress response (GSR) is a widely conserved response that allows
      bacteria to cope with a multitude of stressful conditions. In the past years the
      PhyR-NepR-sigma(EcfG) cascade was identified as the core pathway regulating the
      GSR in Alphaproteobacteria, in which it also plays an important role in bacteria
      host interactions. The regulatory system is composed of the extracytoplasmic
      function sigma factor sigma(EcfG), its anti-sigma factor NepR (for negative
      regulator of the PhyR response), and the anti-sigma factor antagonist PhyR
      (phyllosphere regulator). The three proteins function via a partner-switching
      mechanism that is triggered by PhyR phosphorylation, termed 'sigma factor
      mimicry'. This review will cover core features of the pathway, its physiological
      role, and summarize recent advances towards understanding of the partner
      switching mechanism and of the two-component signaling pathways controlling the
      GSR. 

PMID- 25582887
TI  - The effects of hypochlorous acid and neutrophil proteases on the structure and
      function of extracellular superoxide dismutase.
AB  - Extracellular superoxide dismutase (EC-SOD) is expressed by both macrophages and
      neutrophils and is known to influence the inflammatory response. Upon activation,
      neutrophils generate hypochlorous acid (HOCl) and secrete proteases to combat
      invading microorganisms. This produces a hostile environment in which enzymatic
      activity in general is challenged. In this study, we show that EC-SOD exposed to
      physiologically relevant concentrations of HOCl remains enzymatically active and
      retains the heparin-binding capacity, although HOCl exposure established
      oxidative modification of the N-terminal region (Met32) and the formation of an
      intermolecular cross-link in a fraction of the molecules. The cross-linking was
      also induced by activated neutrophils. Moreover, we show that the neutrophil
      derived proteases human neutrophil elastase and cathepsin G cleaved the N
      terminal region of EC-SOD irrespective of HOCl oxidation. Although the cleavage
      by elastase did not affect the quaternary structure, the cleavage by cathepsin G
      dissociated the molecule to produce EC-SOD monomers. The present data suggest
      that EC-SOD is stable and active at the site of inflammation and that neutrophils
      have the capacity to modulate the biodistribution of the protein by generating EC
      SOD monomers that can diffuse into tissue. 

PMID- 25582886
TI  - Persistent palatable food preference in rats with a history of limited and
      extended access to methamphetamine self-administration.
AB  - Recent studies have shown that when given a mutually exclusive choice between
      cocaine and palatable foods, most rats prefer the non-drug rewards over cocaine.
      Here, we used a discrete choice procedure to assess whether palatable food
      preference generalizes to rats with a history of limited (3 hours/day) or
      extended (6 or 9 hours/day) access to methamphetamine self-administration. On
      different daily sessions, we trained rats to lever-press for either
      methamphetamine (0.1-0.2 mg/kg/infusion) or palatable food (five pellets per
      reward delivery) for several weeks; regular food was freely available. We then
      assessed food-methamphetamine preference either during training, after priming
      methamphetamine injections (0.5-1.0 mg/kg), following a satiety manipulation
      (palatable food exposure in the home cage) or after 21 days of withdrawal from
      methamphetamine. We also assessed progressive ratio responding for palatable food
      and methamphetamine. We found that independent of the daily drug access
      conditions and the withdrawal period, the rats strongly preferred the palatable
      food over methamphetamine, even when they were given free access to the palatable
      food in the home cage. Intake of methamphetamine and progressive ratio responding
      for the drug, both of which increased or escalated over time, did not predict
      preference in the discrete choice test. Results demonstrate that most rats
      strongly prefer palatable food pellets over intravenous methamphetamine,
      confirming previous studies using discrete choice procedures with intravenous
      cocaine. Results also demonstrate that escalation of drug self-administration, a
      popular model of compulsive drug use, is not associated with a cardinal feature
      of human addiction of reduced behavioral responding for non-drug rewards. 

PMID- 25582888
TI  - PRDX6 promotes tumor development via the JAK2/STAT3 pathway in a urethane-induced
      lung tumor model.
AB  - Peroxiredoxin 6 (PRDX6) is a bifunctional protein with both glutathione
      peroxidase (GPx) and iPLA2 activities. Even though several pathophysiological
      functions have been studied, the definitive role of PRDX6 in tumor growth is not
      clear. Here, we compared carcinogen-induced tumor growth in PRDX6-transgenic (Tg)
      mice and non-Tg mice to evaluate the roles of PRDX6 in lung tumor development.
      Urethane (1g/kg)-induced tumor incidence in PRDX6-Tg mice was significantly
      higher compared to non-Tg mice. In the tumors of PRDX6-Tg mice, the activation of
      JAK2/STAT3 and STAT3 DNA binding were also increased, accompanied by increased
      GPx and iPLA2 activities. PRDX6 was colocalized with JAK2 in tumor tissues and
      lung cancer cells and also showed physical interaction with JAK2. We found that
      increasing levels of PRDX6 increase the activation of the JAK2/STAT3 pathway.
      Furthermore, PRDX6-Tg mice showed altered cytokine levels in the tumors,
      especially leading to increased CCL5 levels. We validated that the activation of
      JAK2 was also decreased in lung tumors of CCR5(-/-) mice, and CCL5 increased the
      JAK2/STAT3 pathway in the lung cancer cells. Thus, our findings suggest that
      PRDX6 promotes lung tumor development via its mediated and CCL5-associated
      activation of the JAK2/STAT3 pathway. 

PMID- 25582889
TI  - Percutaneous ultrasonography-guided radiofrequency ablation of hepatocellular
      carcinomas: usefulness of image fusion with three-dimensional ultrasonography.
AB  - AIM: To evaluate the usefulness of fusion imaging with real-time ultrasonography
      (US) and three-dimensional (3D) US for the guidance of radiofrequency ablation
      (RFA) of hepatocellular carcinomas (HCCs) 2-5 cm in diameter. MATERIALS AND
      METHODS: This study was conducted as a retrospective cohort study. It was
      approved by the institutional review board and informed consent was waived.
      During percutaneous RFA of HCCs, targeting was performed under conventional
      fusion imaging guidance, whereas monitoring and controlling were conducted under
      fusion with 3D US guidance. Technical success, technique effectiveness, incidence
      of major complications, and local tumour progression rate were evaluated.
      According to tumour size (small: <3 cm versus medium: 3-5 cm), the roundness
      indexes of the ablation zones and local tumour progression rates were compared.
      RESULTS: There were 29 small-sized HCCs (2.5 +/- 0.3 cm) and 17 medium-sized HCCs
      (3.4 +/- 0.5 cm). All RFA procedures were performed in a single RFA session. Both
      the technical success and technique effectiveness rates were 100%. One patient
      with medium-sized HCC developed a hepatic abscess (n = 1) as a major
      complication. The local tumour progression rate was 8.7% (4/46) with a mean
      follow-up period of 18.2 months. The roundness indexes of the ablation zone were
      not significantly different between small- and medium-sized HCCs, and the local
      tumour progression rates were also not significantly different between the two
      groups [3.4% (1/29) versus 17.6% (3/17); p = 0.135]. CONCLUSION: Image fusion
      with real-time US and 3D US is useful for the guidance of percutaneous RFA for
      HCCs 2-5 cm in diameter.

PMID- 25582890
TI  - Severely impaired health status of non-notified Q fever patients leads to an
      underestimation of the true burden of disease.
AB  - Q fever patients are often reported to experience a long-term impaired health
      status, including fatigue, which can persist for many years. During the large Q
      fever epidemic in The Netherlands, many patients with a laboratory-confirmed
      Coxiella burnetii infection were not notified as acute Q fever because they did
      not fulfil the clinical criteria of the acute Q fever case definition (fever,
      pneumonia and/or hepatitis). Our study assessed and compared the long-term health
      status of notified and non-notified Q fever patients at 4 years after onset of
      illness, using the Nijmegen Clinical Screening Instrument (NCSI). The study
      included 448 notified and 193 non-notified Q fever patients. The most severely
      affected subdomain in both patient groups was 'Fatigue' (50.5% of the notified
      and 54.6% of the non-notified patients had severe fatigue). Long-term health
      status did not differ significantly between the notified and non-notified patient
      groups, and patients scored worse on all subdomains compared to a healthy
      reference group. Our findings suggest that the magnitude of the 2007-2009 Q fever
      outbreak in The Netherlands was underestimated when only notified patients
      according to the European Union case definition are considered. 

PMID- 25582891
TI  - The Impact of Married Individuals Learning HIV Status in Malawi: Divorce, Number
      of Sexual Partners, and Condom Use With Spouses.
AB  - This article assesses how married individuals' knowledge of HIV status gained
      through HIV testing and counseling (HTC) affects divorce, the number of sexual
      partners, and the use of condoms within marriage. This study improves upon
      previous studies on this topic because the randomized incentives affecting the
      propensity to be tested for HIV permit control for selective testing.
      Instrumental variable probit and linear models are estimated, using a randomized
      experiment administered as part of the Malawi Longitudinal Study of Families and
      Health (MLSFH). The results indicate that knowledge of HIV status (1) does not
      affect chances of divorce for either HIV-negative or HIV-positive respondents;
      (2) reduces the number of reported sexual partners among HIV-positive
      respondents; and (3) increases reported condom use with spouses for both HIV
      negative and HIV-positive respondents. These results imply that individuals
      actively respond to information about their HIV status that they learn during
      HTC, invoking protective behavior against future risk of HIV/AIDS for themselves
      and their actual and potential sexual partners. Some limitations of this study
      are a small sample size for those who are HIV-positive and dependence on self
      reported sexual behaviors. 

PMID- 25582892
TI  - Treatment patterns among breast cancer patients in the United States using two
      national surveys on visits to physicians' offices and hospital outpatient
      departments.
AB  - BACKGROUND: Despite the availability of previous studies, little research has
      examined how types of anti-neoplastic agents prescribed differ among various
      populations and health care characteristics in ambulatory settings, which is a
      primary method of providing care in the U.S. Understanding treatment patterns can
      help identify possible disparities and guide practice or policy change.
      OBJECTIVES: To characterize patterns of anti-neoplastic agents prescribed to
      breast cancer patients in ambulatory settings and identify factors associated
      with receipt of treatment. METHODS: A cross-sectional analysis using the National
      Ambulatory Medical Care Survey data in 2006-2010 was conducted. Breast cancer
      treatments were categorized by class and further grouped as chemotherapy,
      hormone, and targeted therapy. A visit-level descriptive analysis using visit
      sampling weights estimated national prescribing trends (n = 2746 breast cancer
      visits, weighted n = 28,920,657). Multiple logistic regression analyses
      identified factors associated with anti-neoplastic agent used. RESULTS: The
      proportion of visits in which anti-neoplastic agent(s) was/were documented
      remained stable from 2006 to 2010 (20.47% vs. 24.56%; P > 0.05). Hormones were
      commonly prescribed (29.69%) followed by mitotic inhibitors (9.86%) and human
      epidermal growth factor receptor2 inhibitors (5.34%). Patients with distant stage
      were more likely than patients with in-situ stage to receive treatment (Adjusted
      Odds Ratio [OR] = 2.79; 95% CI, 1.04-7.77), particularly chemotherapy and
      targeted therapy. Patients with older age, being ethnic minorities, having
      comorbid depression, and having U.S. Medicaid insurance were less likely to
      receive targeted therapy (P < 0.05). Patients with older age, having comorbid
      obesity and osteoporosis were less likely to receive chemotherapy, while patients
      seen in hospital-based settings and settings located in metropolitan areas were
      more likely to receive chemotherapy (P < 0.05). CONCLUSIONS: Anti-neoplastic
      treatment patterns differ among breast cancer patients treated in ambulatory
      settings. Factors predicting treatment include certain socio-demographics, cancer
      stages, comorbidities, metropolitan areas, and setting.

PMID- 25582895
TI  - Oxygen-induced changes to selectivity-determining steps in electrocatalytic CO2
      reduction.
AB  - The state of the electrocatalyst surface-including the oxidation state of the
      catalyst and the presence of spectator species-is investigated on Cu surfaces
      with density functional theory in order to understand predicted ramifications on
      the selectivity and efficiency of CO2 reduction. We examined the presence of
      oxygen-based species, including the fully oxidized Cu2O surface, the partially
      oxidized Cu(110)-(2 * 1)O surface, and the presence of OH spectators. The
      relative oxygen binding strength among these surfaces can help to explain the
      experimentally observed selectivity change between CH4 and CH3OH on these
      electrodes; this suggests that the oxygen-binding strength may be a key parameter
      which predicts the thermodynamically preferred selectivity for pathways
      proceeding through a methoxy (CH3O) intermediate. This study shows the importance
      of the local surface environment in the product selectivity of electrocatalysis,
      and suggests a simple descriptor that can aid in the design of improved
      electrocatalytic materials. 

PMID- 25582893
TI  - Clinical outcomes of Chinese patients with metastatic colorectal cancer receiving
      first-line bevacizumab-containing treatment.
AB  - After the approval of bevacizumab for the first-line treatment of metastatic
      colorectal cancer (mCRC) in China, published information was still limited. This
      observational cohort study enrolled 175 mCRC patients who initiated bevacizumab
      containing first-line chemotherapies at Sun Yet-sen University Cancer Center.
      Backbone chemotherapies included FOLFIRI (45.6 %), FOLFOX (34.9 %), and XELOX
      (19.5 %). Effectiveness data, safety profiles, and treatment patterns were
      collected and compared between oxaliplatin- and irinotecan-based groups. The
      median treatment durations of bevacizumab in first-line and total were equivalent
      between oxaliplatin- and irinotecan-based group (5.0 vs. 4.8 and 6.0 vs. 5.9
      months, respectively). Median progression-free survival (PFS) was 10.6 months,
      and median overall survival (OS) was 24.2 months in entire population. No
      significant difference was found between irinotecan- and oxaliplatin-based groups
      in PFS (10.8 vs. 10.1 months, p = 0.21) or in OS (27.5 vs. 23.7 months, p =
      0.68). Overall response rate in entire population was 38.3 %, and the disease
      control rate was 86.3 %. Bevacizumab-associated serious adverse events included
      hypertension (4.2 %), bleeding (3.6 %), proteinuria (3.0 %), venous
      thromboembolism (0.6 %), and wound-healing complications (0.6 %). Curative-intent
      surgery after conversion chemotherapy was carried out in 23 patients (13.7 %).
      Multivariate analyses showed that maintenance therapy (p = 0.001), resection of
      metastatic sites (p = 0.002), and disease-free interval (p = 0.003) were
      independent prognostic factors for OS survival. In spite of small discrepancies
      in treatment patterns, irinotecan- and oxaliplatin-based chemotherapeutic
      regimens are equally compatible partners for bevacizumab in first-line Chinese
      mCRC treatment. 

PMID- 25582894
TI  - Midwives' perceptions of their role within the context of maternity service
      reform: An Appreciative Inquiry.
AB  - BACKGROUND: In 2010 Australian Government reform of maternity services enabled
      midwives to access Medicare. This significant change provides midwives with new
      opportunities to engage in patterns of working that provide continuity of care to
      childbearing women. There remains limited evidence, however, on midwives
      perceptions of how the reforms impact them both personally and professionally.
      AIM: This research examined midwives' perceptions of their role and how, in light
      of the reform agenda, they might conceptualise a change in working patterns and
      environment to provide greater levels of continuity of care. METHOD: A
      qualitative descriptive approach was employed using the four-stage Appreciative
      Inquiry model. Twenty-three midwives from three maternity units within south-east
      Queensland participated in one of six focus groups. Thematic iterative analysis
      was employed to identify empirical codes and examine relationships within and
      across the data. FINDINGS: Midwives endorsed the reforms and considered the
      concept of continuity of midwifery care as fundamental to achieving a woman
      centred maternity system. Most participants, however, found it difficult to
      conceptualise how they might contribute to any level of system change. In
      addition the majority passively accepted the status quo of their employing
      organisation and believed they were powerless to effect change. CONCLUSION: In
      order to promote the growth of evidence based continuity of care models midwives
      need to work to their full scope of practice. Strong midwifery leadership is
      required to enable midwives to re-conceptualise roles and work patterns and
      identify how they can engage with and contribute to reform of maternity services.

PMID- 25582897
TI  - Jahanyne, an apoptosis-inducing lipopeptide from the marine cyanobacterium
      Lyngbya sp.
AB  - An acetylene-containing lipopeptide, jahanyne, was isolated from the marine
      cyanobacterium Lyngbya sp. Its gross structure was established by spectroscopic
      analyses, and the absolute configuration was clarified based on a combination of
      chiral HPLC analyses, spectroscopic analyses, and derivatization reactions.
      Jahanyne significantly inhibited the growth of human cancer cells and induced
      apoptosis in HeLa cells. 

PMID- 25582896
TI  - Evaluation of diamide insecticides co-applied with other agrochemicals at various
      times to manage Ostrinia nubilalis in processing snap bean.
AB  - BACKGROUND: Multiple applications of pyrethroid insecticides are used to manage
      European corn borer, Ostrinia nubilalis Hubner, in snap bean, but new diamide
      insecticides may reduce application frequency. In a 2 year small-plot study, O.
      nubilalis control was evaluated by applying cyantraniliprole (diamide) and
      bifenthrin (pyrethroid) insecticides at one of three phenological stages (bud,
      bloom and pod formation) of snap bean development. Co-application of these
      insecticides with either herbicides or fungicides was also examined as a way to
      reduce the total number of sprays during a season. RESULTS: Cyantraniliprole
      applications timed either during bloom or during pod formation controlled O.
      nubilalis better than similar timings of bifenthrin. Co-applications of
      insecticides with fungicides controlled O. nubilalis as well as insecticide
      applications alone. Insecticides applied either alone or with herbicides during
      bud stage did not control this pest. CONCLUSION: Diamides are an alternative to
      pyrethroids for the management of O. nubilalis in snap bean. Adoption of diamides
      by snap bean growers could improve the efficiency of production by reducing the
      number of sprays required each season.

PMID- 25582898
TI  - Human herpesvirus-6 infection-associated acute encephalopathy without skin rash.
AB  - BACKGROUND: Human herpesvirus-6 (HHV-6) is the etiological agent of exanthema
      subitum-associated encephalopathy, which usually occurs in children younger than
      3 years. Brain imaging shows various abnormalities. PATIENT: A previously healthy
      4-year-old girl developed acute encephalopathy with clinical features consisting
      of fever, repetitive seizures, and a disturbance of consciousness. The patient
      did not show skin rash suggestive of exanthema subitum during the course of her
      illness. The primary HHV-6 infection was diagnosed based on the absence of IgG
      against HHV-6 and identification of the virus DNA in the acute phase serum and a
      significant increase of the anti-HHV-6 IgG titers in the convalescent phase sera.
      Diffusion-weighted images showed transient high signal intensity in the bilateral
      periventricular white matter and splenium of the corpus callosum and in the gray
      matter structures such as the bilateral basal ganglia and thalami. Upon therapy
      with steroid and gamma-globulin, the patient recovered without any neurological
      deficits. CONCLUSION: Primary HHV-6 infection can cause acute encephalopathy
      without exanthema subitum. The etiological diagnosis is possible only by
      examining the blood and cerebrospinal fluid, when the patient shows no skin rash.
      This condition should be included in the differential diagnosis of acute
      encephalopathy even in patients older than 3 years.

PMID- 25582899
TI  - Classics from The Laryngoscope: celebrating 120 years of impact.

PMID- 25582900
TI  - The building of Urology as a specialty in Mallorca.
AB  - The research of the origin and development of the Medicalhyphen;surgical
      specialties in our environment has been, to my knowledge, limited. The aim of
      this work is to review it in reference to Urology, one of the first specialties
      developed in Mallorca during the second half of the XIX Century and the beginning
      of the XX century. Evidence acquisition has been performed through research of
      the archives of the Royal Academy of Medicine of the Balearic Islands (RAMIB) and
      the Medical College and the study of the Balearic Journal of Medical sciences.
      Furthermore, the biographies of the main precursors and pioneers of Urology in
      Mallorca have been reconstructed. 

PMID- 25582901
TI  - Quality of life of patients with benign prostatic hyperplasia (BPH): endoscopic
      surgery versus laser therapy.
AB  - OBJECTIVE: To compare the results observed in the quality of life of patients
      after transurethral prostate resection (bipolar TUR) or laser therapy. METHODS:
      This is a retrospective observational cohort study: one cohort includes patients
      who underwent endoscopic surgery, and the other patients undergoing laser therapy
      (vaporization). A total of 106 patients were included, divided into two cohorts.
      Two questionnaires were prepared for those who fulfilled inclusion criteria, the
      International Prostate Symptom Score (IPSS), two months before and six months
      after the date of surgery, and Benign Prostate Hyperplasia Patient Impact Measure
      (BPH - PIM) six months after surgery. We consider a statistical significance
      level, p < 0.05% and a confidence interval (CI) of 95%. RESULTS: Mean prostate
      size was 55 cc in the endoscopic surgery cohort versus 40 cc in the laser therapy
      cohort (p = 0.02). 35.8% of patients treated with laser therapy had urinary
      irritative symptoms compared with 6.3% in the endoscopic surgery group (p =
      0.01). Within the laser group, 26.4% of patients had urine leakage compared to
      4.4% among those operated by bipolar TUR (p = 0,03). 86.7% of patients in the
      cohort of bipolar TUR were fully satisfied after surgery compared to 53.6% of the
      laser therapy cohort (p = 0.03). CONCLUSION: In this retrospective observational
      cohort study, the patients of LBO laser therapy cohort had a worse quality of
      life the following six months after surgery compared to those who underwent
      bipolar transurethral resection.

PMID- 25582902
TI  - Decreasing frequency pattern in patients with clean intermittent catheterization
      for bladder voiding dysfunction.
AB  - OBJECTIVES: To evaluate usefulness and morbidity of clean intermittent
      catheterization (CIC) using a decreasing pattern in patients with bladder voiding
      dysfunction (BVD) of varied etiology. METHODS: We performed a retrospective study
      of patients with BVD in whom CIC was indicated. We evaluated the clinical
      presentation, post-void residual urine (PVR), results of the urodynamic studies
      (UDS), and response to CIC in a decreasing pattern, complications espeand patient
      adherence. The primary endpoint was a favorable response to CIC in a decreasing
      frequency pattern. Secondary endpoints were complications and patient perception
      of it. RESULTS: We evaluated a total of 27 patients with BVD. Of these, 15 (56%)
      were women and 12(44%) were men. Mean age was 54.33 years (32-82) and mean follow
      up time was 23.5 months (2-66). The mean catheterized volume and the number of
      catheterizations decreased in all groups of patients. 40.7% of all patients did
      not need to perform catheterization after an average time of 7.38 months. The
      average time to reach a stable PVR or the lack of it was 9.76 months (0.75 to
      63). The only complication recorded were urinary tract infection (UTI) presenting
      as mild cystitis in 7 patients and orchitis in 2 patients. 70.4% (19/27)
      responded to the telephone survey. 79% (15/19) said they have had no major
      difficulty in learning CIC, 52.7% (10/19) said to be continuing CIC, and the mean
      personal rating was 6/10. CONCLUSION: CIC in a decreasing pattern allows almost
      half of the patients to be totally free from catheterization. The other half
      reduces significantly the number of catheterizations, with little interference in
      their daily lives. It is an effective technique, well accepted and well learned
      by most patients with BVD in a wide range of indications, beyond neurogenic
      dysfunction.

PMID- 25582903
TI  - Avanafil for the treatment of erectile dysfunction. An updated review.
AB  - OBJECTIVES: Avanafil is a highly selective phosfosdiesterase 5 inhibitor (PDE5
      inhibitor), with rapid onset of action, approved by the Food and Drug
      Administration (FDA) and the European Medicines Agency for the treatment of
      erectile dysfunction (ED). It had been recently commercialized in Spain. This
      article presents a detailed review of the available literature, where the safety,
      tolerability and efficacy of avanafil were evaluated. METHODS: A systematic
      literature search using the Medline database was performed. The search included
      the terms Avanafil and erectile dysfunction. The pivotal studies of clinical
      development of the drug, and also those randomized, double-blind, placebo
      controlled, well-designed studies were analyzed. We included those studies
      published in English up to January 2014. Likewise, studies of the
      pharmacokinetics and pharmacodynamics of the drug were also included. RESULTS:
      The avanafil pivotal studies, conducted in general population of patients with
      ED, patients with Diabetes mellitus type I and II and patients with ED secondary
      to nerve sparing radical prostatectomy were analyzed. In all these studies,
      avanafil demonstrated a statistically significant improvement in erectile
      function (IIEF), and all the coprimary outcomes (SEP2 and SEP3) compared to
      placebo. Also, a good tolerance profile and few side effects compared to placebo
      were evident. CONCLUSIONS: Avanafil is a selective PDE5 inhibitors, that is
      rapidly absorbed and that has a short time to peak response. It found to be
      effective in randomized, double-blind, placebo-controlled trials conducted in men
      with erectile dysfunction, including in patients with diabetes mellitus and after
      radical prostatectomy. It was generally well tolerated across trials, with very
      few patients withdrawing because of adverse effects. Similarly, avanafil had a
      significantly lower rate of hemodynamic side effects compared with sildenafil.

PMID- 25582904
TI  - Uncommon renal masses: Perirenal extramedullary hematopoiesis and multiple
      lymphangiomatosis with a perirenal lymphangioma.
AB  - OBJECTIVE: To present two cases of infrequent renal masses, trying to achieve the
      diagnosis before surgery. METHODS: We describe a case referred from the
      Department of Hematology in which bilateral perirrenal masses were described in
      the CT scan; after biopsy they where classified as extramedullary hematopoietic
      tissue. The other case was a patient presenting to the emergency room with
      dyspnea. CT Scan showed lungs with multiple cysts, chylothorax and a cystic-solid
      mass in the left perirenal space. In the lung biopsy they reported lung
      lymphangiomatosis, so we didn't perform renal biopsy. RESULTS: Most renal masses
      are renal carcinomas (856%). The less common diagnosis are sarcomas, lymphomas,
      upper urinary tract transitional cell carcinomas, metastases of other primary
      tumors, the Erdheim-Chester disease, the Castleman disease and benign tumors. All
      these diseases might show similar images in the CT scan and MRI, being the biopsy
      and histological study necessary for the diagnosis CONCLUSIONS: Perirenal
      extramedullary hematopoiesis and perirenal lymphangioma are rare diseases that
      need a pathologic study for their diagnosis.

PMID- 25582905
TI  - Urethral adenocarcinoma in a mental deficiency patient.
AB  - OBJECTIVE: To report the case of a urethral tumour in a patient with mental
      deficiency. METHODS/ RESULTS: Complete resection of the tumour was performed and
      the pathologic examination informed the presence of urethral adenocarcinoma. The
      patient is disease-free twelve months after surgery. CONCLUSIONS: Bibliographic
      review for diagnosis and treatment was performed.

PMID- 25582906
TI  - Resection of giant adrenal cortical carcinoma: a case report.
AB  - OBJECTIVE: We report a case of nonfunctioning giant adrenal cortical carcinoma
      undergoing complete resection. METHODS: We report the case and evolution of a
      woman who underwent resection of a giant adrenal carcinoma at Santa Marcelina
      Hospital. RESULTS: A 49-year-old female presented with palpable mass in the right
      hypochondrium extending 5 cm down from the right costal margin. Abdominal CT Scan
      found a large mass occupying the right adrenal region with areas suggestive of
      necrosis, in close contact with the liver, pushing the right kidney inferiorly
      and extending to the midline. Biochemical tests to evaluate hormonal secretion
      resulted in levels within the normal range characteristic of a non-functioning
      adrenal neoplasm. The treatment of choice was resection of the abdominal mass;
      the surgical specimen greatest diameter was 21 cm and weighed 2106 grams. It was
      an adrenal cortical carcinoma. CONCLUSIONS: Options for the treatment of adrenal
      cortical carcinoma showed no significant advances in recent decades and complete
      surgical resection remains the most effective treatment for adrenal cortical
      carcinoma, even in patients with bulky tumor masses.

PMID- 25582908
TI  - Morphological changes of amphiphilic molecular assemblies induced by chemical
      reactions.
AB  - Shape transformations of amphiphilic molecular assemblies induced by chemical
      reactions are studied using coarse-grained molecular simulations. A binding
      reaction between hydrophilic and hydrophobic molecules is considered. It is found
      that the reaction induces transformation of an oil droplet to a tubular vesicle
      via bicelles and vesicles with discoidal arms. The discoidal arms close into
      vesicles, which are subsequently fused into the tubular vesicle. Under the
      chemical reaction, the bicelle-to-vesicle transition occurs at smaller sizes than
      in the absence of the hydrophobic molecules. It is revealed that the enhancement
      of this transition is due to embedded hydrophobic particles that reduce the
      membrane bending rigidity. 

PMID- 25582909
TI  - Processing barley grain with lactic acid and tannic acid ameliorates rumen
      microbial fermentation and degradation of dietary fibre in vitro.
AB  - BACKGROUND: Cereal grains are important ingredients of ruminant diets, but their
      rapid degradation seriously impairs rumen fermentation and the host's health. The
      goal of this study was to evaluate whether processing of barley grain with 1 or
      5% lactic acid (LA) and 1 or 5% tannic acid (TA), without or with an additional
      heat treatment (1% LAH or 1% TAH), may affect microbial ruminal abundance,
      fermentation profile, and nutrient degradation in vitro. RESULTS: Processing with
      LA lowered (P < 0.05) the concentration of short-chain fatty acids (SCFAs),
      proportions of branched-chain SCFA, and the acetate-to-propionate ratio.
      Treatment with 1% TAH and 1% LAH lowered (P < 0.05) gene copy numbers of total
      protozoa, rumen lipopolysaccharide, and degradation of crude protein, and tended
      (P = 0.08) to lower the proportion of the genus Prevotella. Treatment of barley
      grain with 1% LA or 1% LAH stimulated Clostridium cluster XIV. Degradation of
      fibre was enhanced (P < 0.05) by all LA and TA treatments. CONCLUSION: Chemical
      and heat treatment of barley grain modulated the ruminal fermentation profile and
      enhanced fibre degradation; however, processing of grain with LA seems to be
      superior because this effect was not associated with a concomitant depression in
      ruminal degradation of organic matter.

PMID- 25582910
TI  - The signalling mucin Msb2 regulates surface sensing and host penetration via BMP1
      MAP kinase signalling in Botrytis cinerea.
AB  - Botrytis cinerea is a necrotrophic fungus that infects a wide range of fruit,
      vegetable and flower crops. Penetration of the host cuticle occurs via infection
      structures that are formed in response to appropriate plant surface signals. The
      differentiation of these structures requires a highly conserved mitogen-activated
      protein (MAP) kinase cascade including the MAP kinase BMP1. In yeast and several
      plant-pathogenic fungi, the signalling mucin Msb2 has been shown to be involved
      in surface recognition and MAP kinase activation. In this study, a B. cinerea
      msb2 mutant was generated and characterized. The mutant showed normal growth,
      sporulation, sclerotia formation and stress resistance. In the absence of
      nutrients, abnormal germination with multiple germ tubes was observed. In the
      presence of sugars, normal germination occurred, but msb2 germlings were almost
      unable to form appressoria or infection cushions on hard surfaces. Nevertheless,
      the msb2 mutant showed only a moderate delay in lesion formation on different
      host plants, and formed expanding lesions similar to the wild-type. Although the
      wild-type showed increasing BMP1 phosphorylation during the first hours of
      germination on hard surfaces, the phosphorylation levels in the msb2 mutant were
      strongly reduced. Several genes encoding secreted proteins were found to be co
      regulated by BMP1 and Msb2 during germination. Taken together, B. cinerea Msb2 is
      likely to represent a hard surface sensor of germlings and hyphae that triggers
      infection structure formation via the activation of the BMP1 MAP kinase pathway.

PMID- 25582907
TI  - Enhanced transcriptome maps from multiple mouse tissues reveal evolutionary
      constraint in gene expression.
AB  - Mice have been a long-standing model for human biology and disease. Here we
      characterize, by RNA sequencing, the transcriptional profiles of a large and
      heterogeneous collection of mouse tissues, augmenting the mouse transcriptome
      with thousands of novel transcript candidates. Comparison with transcriptome
      profiles in human cell lines reveals substantial conservation of transcriptional
      programmes, and uncovers a distinct class of genes with levels of expression that
      have been constrained early in vertebrate evolution. This core set of genes
      captures a substantial fraction of the transcriptional output of mammalian cells,
      and participates in basic functional and structural housekeeping processes common
      to all cell types. Perturbation of these constrained genes is associated with
      significant phenotypes including embryonic lethality and cancer. Evolutionary
      constraint in gene expression levels is not reflected in the conservation of the
      genomic sequences, but is associated with conserved epigenetic marking, as well
      as with characteristic post-transcriptional regulatory programme, in which sub
      cellular localization and alternative splicing play comparatively large roles. 

PMID- 25582911
TI  - Perspectives in chemistry--aspects of adaptive chemistry and materials.
AB  - Chemistry, pure and applied, is a science and an industry. By its power over the
      expressions of matter, it also displays the creativity of art. It has expanded
      from molecular to supramolecular chemistry and then, by way of constitutional
      dynamic chemistry, towards adaptive chemistry. Constitutional dynamics allow for
      adaptation, through component exchange and selection in response to physical
      stimuli (e.g. light, photoselection), to chemical effectors (e.g. metal ions,
      metalloselection) or to environmental effects (e.g. phase change) in equilibrium
      or out-of-equilibrium conditions, towards the generation of the best
      adapted/fittest constituent(s) in a dynamic set. Such dynamic systems can be
      represented by two-dimensional or three-dimensional dynamic networks that define
      the agonistic and antagonistic relationships between the different constituents
      linked through component exchange. The introduction of constitutional dynamics
      into materials science opens perspectives towards adaptive materials and
      technologies, presenting attractive behavioral features (such as self-healing).
      In particular, dynamic polymers may undergo modification of their properties
      (mechanical, optical, etc.) through component exchange and recombination in
      response to physical or chemical agents. Constitutional adaptive materials open
      towards a systems materials science and offer numerous opportunities for soft
      matter technologies. 

PMID- 25582912
TI  - Importance of C-3 epimer of 25-hydroxyvitamin D in dried blood spots of neonatal
      population.

PMID- 25582914
TI  - Evaluations of dentists on a German physician rating Website: an analysis of the
      ratings.
AB  - BACKGROUND: Physician rating websites have been gaining in importance in both
      practice and research. However, no evidence is available concerning patients'
      ratings of dentists on physician rating websites. OBJECTIVE: The aim of this
      study is to present a comprehensive analysis of the ratings of dentists on a
      German physician rating website over a 2-year period. METHODS: All dentist
      ratings on a German physician rating website (Jameda) from 2012 and 2013 were
      analyzed. The available dataset contained 76,456 ratings of 23,902 dentists from
      72,758 patients. Additional information included the overall score and subscores
      for 5 mandatory questions, the medical specialty and gender of the dentists, and
      the age, gender, and health insurance status of the patients. Statistical
      analysis was conducted using the median test and the Kendall tau-b test. RESULTS:
      During the study period, 44.57% (23,902/53,626) of all dentists in Germany were
      evaluated on the physician rating website, Jameda. The number of ratings rose
      from 28,843 in 2012 to 47,613 in 2013, representing an increase of 65.08%. In
      detail, 45.37% (10,845/23,902) of dentists were rated once, 43.41%
      (10,376/23,902) between 2 and 5 times, and 11.21% (2681/23,902) more than 6 times
      (mean 3.16, SD 5.57). Approximately 90% (21,324/23,902, 89.21%) of dentists
      received a very good or good overall rating, whereas only 3.02% (721/23,902) were
      rated with the lowest scores. Better ratings were given either by female or older
      patients, or by those covered by private health insurance. The best-rated
      specialty was pediatric dentistry; the lowest ratings were given to
      orthodontists. Finally, dentists were rated slightly lower in 2013 compared to
      2012 (P=.01). CONCLUSIONS: The rise in the number of ratings for dentists
      demonstrates the increasing popularity of physician rating websites and the need
      for information about health care providers. Future research should assess
      whether social media, especially Web-based ratings, are suitable in practice for
      patients and other stakeholders in health care (eg, insurance providers) to
      reflect the clinical quality of care.

PMID- 25582913
TI  - Neural mechanisms controlling seasonal reproduction: principles derived from the
      sheep model and its comparison with hamsters.
AB  - Seasonal reproduction is a common adaptive strategy among mammals that allows for
      breeding to occur at times of the year when it is most advantageous for the
      subsequent survival and growth of offspring. A major mechanism responsible for
      seasonal reproduction is a striking increase in the responsiveness of
      gonadotropin-releasing hormone (GnRH) neurons to the negative feedback effects of
      estradiol. The neural and neuroendocrine circuitry responsible for mammalian
      seasonal reproduction has been primarily studied in three animal models: the
      sheep, and two species of hamsters. In this review, we first describe the
      afferent signals, neural circuitry and transmitters/peptides responsible for
      seasonal reproductive transitions in sheep, and then compare these mechanisms
      with those derived from studies in hamsters. The results suggest common
      principles as well as differences in the role of specific brain nuclei and
      neuropeptides, including that of kisspeptin cells of the hypothalamic arcuate
      nucleus, in regulating seasonal reproduction among mammals. 

PMID- 25582915
TI  - Stabilizing the false vacuum: Mott skyrmions.
AB  - Topological excitations keep fascinating physicists since many decades. While
      individual vortices and solitons emerge and have been observed in many areas of
      physics, their most intriguing higher dimensional topological relatives,
      skyrmions (smooth, topologically stable textures) and magnetic monopoles emerging
      almost necessarily in any grand unified theory and responsible for charge
      quantization remained mostly elusive. Here we propose that loading a three
      component nematic superfluid such as (23)Na into a deep optical lattice and
      thereby creating an insulating core, one can create topologically stable skyrmion
      textures. The skyrmion's extreme stability and its compact geometry enable one to
      investigate the skyrmion's structure, and the interplay of topology and
      excitations in detail. In particular, the superfluid's excitation spectrum as
      well as the quantum numbers are demonstrated to change dramatically due to the
      skyrmion, and reflect the presence of a trapped monopole, as imposed by the
      skyrmion's topology. 

PMID- 25582917
TI  - Quantum cosmology: a review.
AB  - In quantum cosmology, one applies quantum physics to the whole universe. While no
      unique version and no completely well-defined theory is available yet, the
      framework gives rise to interesting conceptual, mathematical and physical
      questions. This review presents quantum cosmology in a new picture that tries to
      incorporate the importance of inhomogeneity. De-emphasizing the traditional
      minisuperspace view, the dynamics is rather formulated in terms of the interplay
      of many interacting 'microscopic' degrees of freedom that describe the space-time
      geometry. There is thus a close relationship with more-established systems in
      condensed-matter and particle physics even while the large set of space-time
      symmetries (general covariance) requires some adaptations and new developments.
      These extensions of standard methods are needed both at the fundamental level and
      at the stage of evaluating the theory by effective descriptions. 

PMID- 25582916
TI  - Gastrodin alleviates cerebral ischemic damage in mice by improving anti-oxidant
      and anti-inflammation activities and inhibiting apoptosis pathway.
AB  - Gastrodin (GAS), an active constituent of the Chinese herbal medicine Tianma, has
      anti-oxidant and anti-inflammation activities but its protective effect to the
      prevention of neurotoxicity induced by ischemic stroke is unclear. In the present
      study, middle cerebral artery occlusion (MCAO) was used to establish a mice
      ischemic stroke model. Infarct volume ratio and neurobehavioral score were
      evaluated, Nissl staining was performed and the expression of cleaved Caspase 3,
      Bax and B cell lymphoma 2 (Bcl-2) were assessed at 24 h or 7 days after
      reperfusion. In addition, the total superoxide dismutase (SOD) activity and
      malondialdehyde (MDA) content, as well as the expression of Nuclear factor
      erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), SOD1, phospho-Akt
      and total Akt and TNF-alpha and IL-1beta in the ischemic hemispheres were also
      observed at 6 h after reperfusion to assess oxidative stress and inflammatory
      changes after GAS treatment. It was found that GAS, especially at high dose (100
      mg/kg) reduced tested neuronal injury and neurobehavioral deficient in MCAO mice.
      Enhanced expression of cleaved Caspase 3 and Bax and decreased expression of Bcl
      2 by MCAO were also reversed by GAS. Moreover, GAS treatment decreased the MDA
      content and the expression of TNF-alpha and IL-1beta, and increased amount of SOD
      activity and the expression of HO-1 and SOD1 in GAS-treated ischemic brain.
      Furthermore, GAS significantly increased Akt phosphorylation and Nrf2 expression.
      These results support the neuroprotective effects of GAS, and the activation of
      Akt/Nrf2 pathway may play a critical role in the pharmacological action of GAS.

PMID- 25582920
TI  - Protecting group free enantiospecific total syntheses of structurally diverse
      natural products of the tetrahydrocannabinoid family.
AB  - A simple, highly diastereoselective, Lewis acid catalyzed Friedel-Crafts coupling
      of a cyclic allylic alcohol with resorcinol derivatives has been developed. The
      method was applied for the enantiospecific total syntheses of structurally
      diverse natural products such as machaeriol-D, Delta(8)-THC, Delta(9)-THC, epi
      perrottetinene and their analogues. Synthesis of both natural products and their
      enantiomers has been achieved with high atom economy, in a protecting group free
      manner and in less than 6 steps, the longest linear sequence, in a very good
      overall yield starting from R-(+) and S-(-)-limonene. 

PMID- 25582919
TI  - Bovine respiratory syncytial virus and bovine coronavirus in Swedish organic and
      conventional dairy herds.
AB  - BACKGROUND: Infections with bovine respiratory syncytial virus (BRSV) and bovine
      coronavirus (BoCV) are endemic to the cattle populations in most countries,
      causing respiratory and/or enteric disease. It has been demonstrated that herds
      can remain free from these infections for several years also in high prevalence
      areas. Organically managed (OM) dairy herds have been shown to have lower
      seroprevalence of both viruses compared to conventionally managed (CM) herds. The
      objective of this study was to challenge the hypothesis of a lower occurrence of
      BRSV and BoCV in OM compared to CM dairy herds. In November 2011, May 2012 and
      May 2013 milk samples from four homebred primiparous cows were collected in 75 to
      65 OM and 69 to 62 CM herds. The antibody status regarding BRSV and BoCV was
      analysed with commercial indirect ELISAs. Herds were classified as positive if at
      least one individual sample was positive. RESULTS: The prevalence of positive
      herds ranged from 73.4% to 82.3% for BRSV and from 76.8% to 85.3% for BoCV among
      OM and CM herds, over the three sampling occasions. There was no statistically
      significant difference between OM and CM herds at any sampling occasion. The
      incidence risk of newly infected herds did not differ statistically between OM
      and CM herds at any sampling occasion, neither for BRSV nor for BoCV. The
      incidence of herds turning sero-negative between samplings corresponded to the
      incidence of newly infected. Bulk tank milk (BTM) samples were also sampled in
      the herds and analysed. Several herds were negative on individual samples but
      positive in BTM. Herd-level data on production, health and reproduction were
      retrieved from VAXA Sweden and the study herds were representative of the source
      population. CONCLUSION: There was no difference in prevalence of or incidence
      risk for BRSV or BoCV between Swedish OM and CM herds. Because the incidence of
      herds becoming seropositive was balanced by herds becoming seronegative it should
      be possible to lower the prevalence of these two infections among Swedish dairy
      cattle herds if biosecurity is improved.

PMID- 25582918
TI  - Involvement of the H1 Histamine Receptor, p38 MAP Kinase, Myosin Light Chains
      Kinase, and Rho/ROCK in Histamine-Induced Endothelial Barrier Dysfunction.
AB  - OBJECTIVE: The mechanisms by which histamine increases microvascular permeability
      remain poorly understood. We tested the hypothesis that H1 receptor activation
      disrupts the endothelial barrier and investigated potential downstream signals.
      METHODS: We used confluent EC monolayers, assessing TER as an index of barrier
      function. HUVEC, HCMEC, and HDMEC were compared. Receptor expression was
      investigated using Western blotting, IF confocal microscopy and RT-PCR. Receptor
      function and downstream signaling pathways were tested using pharmacologic
      antagonists and inhibitors, respectively. RESULTS: We identified H1-H4 receptors
      on all three EC types. H1 antagonists did not affect basal TER but prevented the
      histamine-induced decrease in TER. Blockade of H2 or H3 attenuated the histamine
      response only in HDMEC, while inhibition of H4 attenuated the response only in
      HUVEC. Combined inhibition of both PKC and PI3K caused exaggerated histamine
      induced barrier dysfunction in HDMEC, whereas inhibition of p38 MAP kinase
      attenuated the histamine response in all three EC types. Inhibition of RhoA,
      ROCK, or MLCK also prevented the histamine-induced decrease in TER in HDMEC.
      CONCLUSION: The data suggest that multiple signaling pathways contribute to
      histamine-induced endothelial barrier dysfunction via the H1 receptor.

PMID- 25582921
TI  - Estimating the number of sex workers in South Africa: rapid population size
      estimation.
AB  - Although recognized as a vulnerable population, there is no national population
      size estimate for sex workers in South Africa. A rapid sex worker enumeration
      exercise was undertaken in twelve locations across the country based on
      principles of participatory mapping and Wisdom of the Crowd. Sites with a range
      of characteristics were selected, focusing on level of urbanisation, trucking,
      mining and borders. At each site, sex worker focus groups mapped local hotspots.
      Interviews with sex workers at identified hotspots were used to estimate the
      numbers and genders of sex workers working in each. Estimates provided in the
      literature were combined with enumeration exercise results to define assumptions
      that could be applied to a national extrapolation. A working estimate was reached
      of between 131,000 and 182,000 sex worker in South Africa, or between 0.76 and 1
      % of the adult female population. The success of the exercise depended on
      integral involvement of sex worker peer educators and strong ethical
      considerations.

PMID- 25582922
TI  - Fusobacterium and Escherichia: models of colorectal cancer driven by microbiota
      and the utility of microbiota in colorectal cancer screening.
AB  - Intestinal microbiota has emerging roles in the development of colorectal cancer
      (CRC). Intestinal dysbiosis, with altered levels of specific bacteria, is
      consistently seen in CRC. The heart of the debate lies in whether these bacteria
      are a cause or consequence of CRC. Two bacteria in particular, Fusobacterium
      nucleatum and Escherichia coli, have consistently been associated with CRC. This
      review will examine evidence supporting oncogenic roles of F. nucleatum and E.
      coli. The proposed mechanisms of tumor formation follow two models: bacterial
      induced chronic inflammation leads to cell proliferation and tumor formation and
      virulence factors directly induce tumor formation. This review will further
      examine the potential for microbiota as biomarkers in CRC, with a focus on F.
      nucleatum. 

PMID- 25582923
TI  - Orthopedic registry research - limitations and future perspectives.

PMID- 25582924
TI  - Analysis of the safety profile of treatment with a large number of shock waves
      per session in extracorporeal lithotripsy.
AB  - OBJECTIVE: To assess the safety of increasing the number of waves per session in
      the treatment of urolithiasis using extracorporeal lithotripsy. MATERIAL AND
      METHODS: Prospective, comparative, nonrandomized parallel study of patients with
      renoureteral lithiasis and an indication for extracorporeal lithotripsy who were
      consecutively enrolled between 2009 and 2010. We compared group I (160 patients)
      treated on schedule with a standard number of waves/session (mean 2858,3+/-302,8)
      using a Dornier lithotripter U/15/50 against group II (172 patients) treated with
      an expanded number of waves/session (mean, 6728,9+/-889,6) using a Siemens
      Modularis lithotripter. The study variables were age, sex, location, stone size,
      number of waves/session and total number of waves to resolution, stone-free rate
      (SFR) and rate of complications (Clavien-Dindo classification). Student's t-test
      and the chi-squared test were employed for the statistical analysis. RESULTS: The
      total rate of complications was 11.9% and 10.46% for groups I and II,
      respectively (P=.39). All complications were minor (Clavien-Dindo grade I). The
      most common complications were colic pain and hematuria in groups I and II,
      respectively, with a similar treatment intolerance rate (P>.05). The total number
      of waves necessary was lower in group II than in group I (P=.001), with SFRs of
      96.5% and 71.5%, respectively (P=.001). CONCLUSION: Treatment with an expanded
      number of waves per session in extracorporeal lithotripsy does not increase the
      rate of complications or their severity. However, it could increase the overall
      effectiveness of the treatment.

PMID- 25582925
TI  - Surgical site infections in patients who undergo radical cystectomy: Excess
      mortality, stay prolongation and hospital cost overruns.
AB  - BACKGROUND: The aim of this study was to analyze the impact of surgical site
      infections (SSI) in patients who underwent radical cystectomy, in terms of excess
      hospital mortality, stay prolongation and cost overruns. MATERIAL AND METHODS: A
      retrospective observational study was conducted on a sample of patients who
      underwent radical cystectomy as recorded in the basic minimum data sets of 87
      Spanish hospitals from 2008-2010. RESULTS: We studied 4377 patients who underwent
      radical cystectomy (3904 men and 473 women) of whom 849 (19.4%) experienced an
      SSI. The patients with SSI were predominantly men, elderly and had a higher
      prevalence of alcohol-related disorders and more comorbidities. The patients with
      SSI had significant excess mortality (125.6%), undue stay prolongation (17.8
      days) and cost overruns (14,875.70 euros). CONCLUSIONS: After controlling for
      demographic variables, hospital type, addiction disorders and comorbidities using
      multivariate pairing, the onset of SSI in patients who underwent radical
      cystectomy significantly increased the mortality, stay and cost. Certain
      preventive measures already established in previous studies could reduce the
      incidence of SSI and its healthcare and financial impact.

PMID- 25582926
TI  - Factors that influence the urodynamic results of botulinum toxin in the treatment
      of neurogenic hyperactivity.
AB  - OBJECTIVES: To determine the urodynamic efficacy and factors that influence the
      urodynamic results of treatment of neurogenic detrusor hyperactivity with
      intradetrusor injection of botulinum toxin type A (BTX-A) in patients with spinal
      cord injury (SCI). MATERIAL AND METHODS: A retrospective study was conducted with
      a cohort of 70 patients composed of 40 men and 30 women with stable SCI (mean
      age, 39 +/- 13.3 years) who underwent an intradetrusor injection of 300 IUs of
      BTX-A. A urodynamic study was conducted prior to the injection and 6 +/- 4.3
      months after the treatment. New urodynamic studies were subsequently performed up
      to an interval of 16 +/- 12.2 months. RESULTS: The BTX-A significantly increased
      (p < .05) the cystomanometric bladder capacity, the bladder volume of the first
      involuntary contraction of the detrusor and the postvoid residue. We observed a
      decrease that tended towards statistical significance (p < .1) of the maximum
      detrusor pressure and the maximum urine flow. Neither the bladder accommodation
      nor the urethral resistance index (bladder outlet obstruction index) varied
      significantly. The increase in vesical capacity was maintained in 50% of the
      sample for more than 32 months. Age, sex, anticholinergic treatment and lesion
      age showed no influence in terms of the increase in bladder capacity. The
      indwelling urinary catheter (IUC) was the only statistically significant negative
      factor. CONCLUSIONS: The urodynamic effect of BTX-A is maintained for a
      considerable time interval. The IUC negatively influences the result of the
      treatment.

PMID- 25582928
TI  - First report of Enterocytozoon bieneusi in pigs in Brazil.
AB  - Although Brazil is the world's fourth largest producer and exporter of pork,
      there is no information on Enterocytozoon bieneusi in pigs. This study was
      undertaken to determine the presence of E. bieneusi in pigs in the State of Rio
      de Janeiro, Brazil. Fecal samples were collected from 91 pigs (1- to 12-month
      old) in 10 properties and examined by molecular methods. The presence of E.
      bieneusi was determined by PCR and all PCR positive specimens were sequenced to
      determine the genotype by nucleotide sequence analysis of the internal
      transcribed spacer of the rRNA gene. E. bieneusi was found in pigs in all farms.
      Fifty four (59.3%) samples were E. bieneusi-positive. A wide genetic diversity
      was found with 21 genotypes identified, 4 previously reported (O, EbpA, CS-1, and
      H) and 17 novel genotypes named PigEb1-PigEb17. All 17 novel genotypes identified
      in this study clustered within the previously designated zoonotic Group 1. The
      most prevalent genotypes were novel genotypes PigEb2 and PigEb4 (16/91, 17.6%,
      each). Mixed infections with 2 or 3 genotypes were detected in 13 pigs (24.1%).
      The high prevalence in pigs observed in this study, the description of two known
      zoonotic genotypes (EbpA and O), and the report of 17 new genotypes of E.
      bieneusi, represent an important advancement in the study of the wide genetic
      diversity of this organism, emphasizing the importance of further research,
      especially in geographical areas where little or no research has been conducted.
      The zoonotic risk of these novel genotypes and their importance to other animal
      species is still unknown, but needs to be further evaluated. 

PMID- 25582929
TI  - Selective elimination of Leptomonas from the in vitro co-culture with Leishmania.
AB  - Leishmania and Leptomonas are protozoan parasites of the family Trypanosomatidae.
      Leishmania donovani causes the fatal visceral leishmaniasis (VL; kala-azar) in
      mammals and is transmitted by sand fly vector. Certain VL-cured human populations
      in India and Sudan develop post kala-azar dermal leishmaniasis (PKDL) due to the
      same parasite. Although Leptomonas is parasitic mainly in insects, several recent
      reports on the clinical isolates of L. donovani from VL and PKDL patients in
      India confirm co-infection of Leptomonas seymouri, probably due to immune
      suppression in those individuals. Detection of L. seymouri in the in vitro
      cultures of L. donovani from clinical origin is difficult due to many
      similarities between L. seymouri and L. donovani. We describe here ways to detect
      L. seymouri and L. donovani in co-culture. In addition, based on our observation
      regarding the growth of L. seymouri in different culture conditions, we report
      here a novel procedure, which can selectively eliminate L. seymouri from the in
      vitro co-culture with L. donovani. This would be beneficial to researchers who
      prefer to deal with pure populations of Leishmania parasites for various
      downstream immunological and genetic studies. 

PMID- 25582931
TI  - Robot-assisted laparoscopic approach for artificial urinary sphincter
      implantation in 11 women with urinary stress incontinence: surgical technique and
      initial experience.
AB  - BACKGROUND: Artificial urinary sphincter (AUS) implantation is recommended for
      women suffering urinary stress incontinence. Robot-assisted laparoscopy allows
      improved dexterity and visibility compared to traditional laparoscopy,
      potentially providing significant advantages for deep pelvic surgery. OBJECTIVE:
      To report our surgical technique and initial experience in transperitoneal robot
      assisted laparoscopic AUS implantation in women with urinary stress incontinence.
      DESIGN, SETTING, AND PARTICIPANTS: Eleven eligible patients with AUS implantation
      or revision using robot-assisted laparoscopy for urinary stress incontinence were
      included between January 2012 and February 2014 at Department of Urology, Lille
      University Hospital. SURGICAL TECHNIQUE: Procedures were performed with the
      assistance of a four-arm da Vinci robot. The urethrovaginal space was dissected
      after transperitoneal access to the Retzius space. An 11-mm port placed in the
      right iliac fossa allowed introduction of the AUS device. The cuff and balloon
      tubes were externalised via a 5-mm suprapubic incision. The peritoneum was
      finally sutured. MEASUREMENTS: Clinical data were prospectively collected before,
      during, and after the procedure. Results were classified as complete continence
      (no leakage and no pad usage), social continence (leakage and/or pad usage with
      no impact on social life), or failure (leakage and/or pad usage impacting social
      life). RESULTS AND LIMITATIONS: After mean follow-up of 17.6 mo (interquartile
      range 10.8-26 mo), eight patients (72.7%) had a successful AUS implantation, of
      whom seven (87.5%) reported complete continence and one had social continence.
      Two vaginal injuries and two bladder injuries occurred intraoperatively. Two
      patients experienced early minor postoperative complications and two had a major
      postoperative complication. CONCLUSIONS: Robot-assisted laparoscopic AUS
      implantation is a feasible procedure. Further studies will better assess the
      place of robot-assisted laparoscopy in AUS implantation. PATIENT SUMMARY: We
      investigated the treatment of 11 patients with stress urinary incontinence using
      robot-assisted implantation of an artificial urinary sphincter (AUS). The results
      show that the procedure is feasible procedure, and future studies will to help
      assess the place of robot-assisted laparoscopy in AUS implantation.

PMID- 25582930
TI  - Best practices in robot-assisted radical cystectomy and urinary reconstruction:
      recommendations of the Pasadena Consensus Panel.
AB  - CONTEXT: Robot-assisted surgery is increasingly used for radical cystectomy (RC)
      and urinary reconstruction. Sufficient data have accumulated to allow evidence
      based consensus on key issues such as perioperative management, comparative
      effectiveness on surgical complications, and oncologic short- to midterm
      outcomes. OBJECTIVE: A 2-d conference of experts on RC and urinary reconstruction
      was organized in Pasadena, California, and the City of Hope Cancer Center in
      Duarte, California, to systematically review existing peer-reviewed literature on
      robot-assisted RC (RARC), extended lymphadenectomy, and urinary reconstruction.
      No commercial support was obtained for the conference. EVIDENCE ACQUISITION: A
      systematic review of the literature was performed in agreement with the PRISMA
      statement. EVIDENCE SYNTHESIS: Systematic literature reviews and individual
      presentations were discussed, and consensus on all key issues was obtained. Most
      operative, intermediate-term oncologic, functional, and complication outcomes are
      similar between open RC (ORC) and RARC. RARC consistently results in less blood
      loss and a reduced need for transfusion during surgery. RARC generally requires
      longer operative time than ORC, particularly with intracorporeal reconstruction.
      Robotic assistance provides ergonomic value for surgeons. Surgeon experience and
      institutional volume strongly predict favorable outcomes for either open or
      robotic techniques. CONCLUSIONS: RARC appears to be similar to ORC in terms of
      operative, pathologic, intermediate-term oncologic, complication, and most
      functional outcomes. RARC consistently results in less blood loss and a reduced
      need for transfusion during surgery. RARC can be more expensive than ORC,
      although high procedural volume may attenuate this difference. PATIENT SUMMARY:
      Robot-assisted radical cystectomy (RARC) is an alternative to open surgery for
      patients with bladder cancer who require removal of their bladder and
      reconstruction of their urinary tract. RARC appears to be similar to open surgery
      for most important outcomes such as the rate of complications and intermediate
      term cancer-specific survival. Although RARC has some ergonomic advantages for
      surgeons and may result in less blood loss during surgery, it is more time
      consuming and may be more expensive than open surgery.

PMID- 25582932
TI  - Subcomponent self-assembly of a 4 nm M4 L6 tetrahedron with Zn(II) vertices and
      perylene bisimide dye edges.
AB  - Formation of a tetrahedron with >4 nm perylene bisimide (PBI) dye edges and
      Zn(II) vertices in a one-pot 22 component self-assembly reaction is reported. The
      luminescent polyhedron equilibrates to a Zn2 L3 helicate and disassembles upon
      dilution. Insights into the subcomponent self-assembly of extended PBI ligands
      help to refine design rules for constructing large photofunctional
      metallosupramolecular hosts.

PMID- 25582927
TI  - HIV-2 infects resting CD4+ T cells but not monocyte-derived dendritic cells.
AB  - BACKGROUND: Human Immunodeficiency Virus-type 2 (HIV-2) encodes Vpx that degrades
      SAMHD1, a cellular restriction factor active in non-dividing cells. HIV-2
      replicates in lymphocytes but the susceptibility of monocyte-derived dendritic
      cells (MDDCs) to in vitro infection remains partly characterized. RESULTS: Here,
      we investigated HIV-2 replication in primary CD4+ T lymphocytes, both activated
      and non-activated, as well as in MDDCs. We focused on the requirement of Vpx for
      productive HIV-2 infection, using the reference HIV-2 ROD strain, the proviral
      clone GL-AN, as well as two primary HIV-2 isolates. All HIV-2 strains tested
      replicated in activated CD4+ T cells. Unstimulated CD4+ T cells were not
      productively infected by HIV-2, but viral replication was triggered upon
      lymphocyte activation in a Vpx-dependent manner. In contrast, MDDCs were poorly
      infected when exposed to HIV-2. HIV-2 particles did not potently fuse with MDDCs
      and did not lead to efficient viral DNA synthesis, even in the presence of Vpx.
      Moreover, the HIV-2 strains tested were not efficiently sensed by MDDCs, as
      evidenced by a lack of MxA induction upon viral exposure. Virion pseudotyping
      with VSV-G rescued fusion, productive infection and HIV-2 sensing by MDDCs.
      CONCLUSION: Vpx allows the non-productive infection of resting CD4+ T cells, but
      does not confer HIV-2 with the ability to efficiently infect MDDCs. In these
      cells, an entry defect prevents viral fusion and reverse transcription
      independently of SAMHD1. We propose that HIV-2, like HIV-1, does not productively
      infect MDDCs, possibly to avoid triggering an immune response mediated by these
      cells.

PMID- 25582933
TI  - A model-informed rank test for right-censored data with intermediate states.
AB  - The generalized Wilcoxon and log-rank tests are commonly used for testing
      differences between two survival distributions. We modify the Wilcoxon test to
      account for auxiliary information on intermediate disease states that subjects
      may pass through before failure. For a disease with multiple states where
      patients are monitored periodically but exact transition times are unknown (e.g.
      staging in cancer), we first fit a multi-state Markov model to the full data set;
      when censoring precludes the comparison of survival times between two subjects,
      we use the model to estimate the probability that one subject will have survived
      longer than the other given their censoring times and last observed status, and
      use these probabilities to compute an expected rank for each subject. These
      expected ranks form the basis of our test statistic. Simulations demonstrate that
      the proposed test can improve power over the log-rank and generalized Wilcoxon
      tests in some settings while maintaining the nominal type 1 error rate. The
      method is illustrated on an amyotrophic lateral sclerosis data set.

PMID- 25582935
TI  - The journal in 2014.

PMID- 25582934
TI  - Myelotoxicity of carboplatin is increased in vivo in db/db mice, the animal model
      of obesity-associated diabetes mellitus.
AB  - PURPOSE: Some authors observed increased carboplatin-associated myelotoxicity in
      obese patients which was exclusively attributed to elevated AUC. To investigate
      the potential contribution of functional changes of cells primarily responsible
      for myelopoiesis, granulocyte-macrophage progenitors (CFU-GM) were studied in
      obesity-associated diabetes mellitus (DMT2). METHODS: The most frequently used
      animal model of human obesity with DMT2 is db/db mouse. Cellularity, frequency of
      CFU-GM and total CFU-GM content of femoral bone marrow were measured after 100
      mg/kg dose of carboplatin in vivo. To exclude influence of pharmacokinetic
      changes, direct toxicity of carboplatin on CFU-GM was also determined in vitro
      and was compared with other anticancer agents, namely doxorubicin, 5-fluorouracil
      and 4-thiouridylate. RESULTS: After intraperitoneal administration of
      carboplatin, each measured characteristics of bone marrow function was more
      significantly suppressed and the induced neutropenia was more serious in db/db
      mice than in the controls. The increased myelotoxicity seemed to be a direct
      effect on myeloid progenitor cells since their increased in vitro sensitivity was
      found in db/db mice. This was not specific for carboplatin, a similar double to
      fivefold increase in myelotoxicity of each cytotoxic drug with different
      mechanism of action was observed. Four-thiouridylate, a promising antileukemic
      molecule with good therapeutic index, was by far the least toxic for CFU-GM of
      db/db mice. CONCLUSIONS: A serious disorder of CFU-GM progenitors was suggested
      in obese mice with DMT2, which eventually might lead to more severe myelotoxicity
      and neutropenia. Weight loss and normalization of glucose homeostasis may be
      important before chemotherapy of malignant diseases in obesity with DMT2.

PMID- 25582937
TI  - Colorectal cancer screening.
AB  - Colorectal cancer is one of the most common malignancies in Australia, and
      screening to detect it an earlier stage is cost-effective. Furthermore, detection
      and removal of precursor polyps can reduce incidence. Currently, there are
      limited data to determine the screening rate in Australia, but it is certainly
      lower than the 80% screening rate considered desirable. Whether colonoscopy is
      used as the screening test or to follow up positive results of an initial non
      invasive test, it plays a fundamental role. Despite high sensitivity and
      specificity, it is expensive and invasive with measurable risk and is not
      acceptable as an initial test to many participants. It does not provide complete
      protection, and interval cancers between planned colonoscopies are associated
      with proximal location, origin in sessile serrated adenomas and operator
      dependent factors. An essential component of colorectal screening is the
      measurement of colonoscopy quality indicators, such as caecal intubation and
      adenoma detection rates, which are known to be associated with the rate of
      interval cancer. The non-invasive screening test currently recommended in
      Australia is biennial testing for faecal occult blood between the ages of 50 and
      75 using a faecal immunochemical test, with positives evaluated by colonoscopy.
      This is provided through the National Bowel Cancer Screening Programme, currently
      for those at the ages of 50, 55, 60 and 65 years, with full implementation of
      biennial screening by 2020. To improve screening in Australia, the most fruitful
      approach may be to acknowledge that there is a choice of screening tests and to
      focus on the goal of improving overall participation rate and being able to
      measure this.

PMID- 25582938
TI  - Treatment of patients with multiple myeloma who are eligible for stem cell
      transplantation: position statement of the Myeloma Foundation of Australia
      Medical and Scientific Advisory Group.
AB  - The survival of patients with multiple myeloma (MM) has improved substantially
      since the introduction in the late 1980s of high-dose chemotherapy (HDT)
      supported by autologous stem cell transplantation (ASCT). Further improvements
      have been observed following the availability of immunomodulatory drugs (IMiD)
      such as thalidomide and lenalidomide, and the proteasome inhibitor, bortezomib.
      Here, we summarise the recommendations of the Medical Scientific Advisory Group
      to the Myeloma Foundation of Australia for patients considered suitable for HDT +
      ASCT as part of initial therapy. These recommendations incorporate the various
      phases of treatment: induction, HDT conditioning and maintenance therapy.

PMID- 25582939
TI  - Statin utilisation patterns in older Australians living in residential care: 1
      year prevalence study.
AB  - Despite controversy over the risks and benefits of statin therapy, statins
      continue to be commonly used medicines by older people. In a cohort study of
      participants aged >=70 years (n = 540) living in residential care, Sydney, we
      found that the proportion of statin users decreased gradually from the baseline
      of 33.1% to 31.3% at 6 months (P = 0.13) and to 28.7% over 1 year (P = 0.002).
      Prevalence of statin use decreased with increasing age, with individuals aged
      >=90 years being more likely to discontinue or deprescribe statins. The patterns
      of statin use did not change according to increasing baseline dose or baseline
      indication.

PMID- 25582940
TI  - Leprosy: diagnosis and management in a developed setting.
AB  - Leprosy remains an important global health concern, but little has been published
      about its diagnosis and management in developed settings. It has been postulated
      that delay in diagnosis is common in developed settings. We reviewed all the
      cases of leprosy seen at a major tertiary referral centre between 1999 and 2013
      and demonstrated that delay in diagnosis is common, especially when patients
      present with symptoms of leprosy reactions rather than classical symptoms, such
      as hypo-pigmented hypo-aesthetic skin lesions and neuropathy.

PMID- 25582941
TI  - Who really knows their patients' penicillin adverse drug reaction status? A cross
      sectional survey.
AB  - This cross-sectional survey of patients with adverse drug reactions (ADR) to
      penicillin and their treating doctor, nurse and pharmacist was undertaken to
      identify the extent of healthcare workers (HCW) awareness of their patients' ADR,
      and antibiotic use in hospital. There were 23 (38%) doctors, 53 (87%) nurses and
      40 (66%) pharmacists who were aware of their patient's penicillin ADR, despite
      more than half of their patients receiving antibiotics. Interventions encouraging
      'double checking' may improve antibiovigilance.

PMID- 25582942
TI  - Restrictive cardiomyopathy as a result of endomyocardial fibrosis from
      hypereosinophilia.

PMID- 25582943
TI  - Olmesartan-induced enteropathy.

PMID- 25582944
TI  - Acute adrenal failure due to bilateral adrenal haemorrhage associated with lupus
      anticoagulant antibodies.

PMID- 25582945
TI  - 'Formalising the form?': safety and quality concerns with not for resuscitation
      documentation.

PMID- 25582946
TI  - Molecules-oligomers-nanowires-graphene nanoribbons: a bottom-up stepwise on
      surface covalent synthesis preserving long-range order.
AB  - We report on a stepwise on-surface polymerization reaction leading to oriented
      graphene nanoribbons on Au(111) as the final product. Starting from the precursor
      4,4"-dibromo-p-terphenyl and using the Ullmann coupling reaction followed by
      dehydrogenation and C-C coupling, we have developed a fine-tuned, annealing
      triggered on-surface polymerization that allows us to obtain an oriented nanomesh
      of graphene nanoribbons via two well-defined intermediate products, namely, p
      phenylene oligomers with reduced length dispersion and ordered submicrometric
      molecular wires of poly(p-phenylene). A fine balance involving gold catalytic
      activity in the Ullmann coupling, appropriate on-surface molecular mobility, and
      favorable topochemical conditions provided by the used precursor leads to a high
      degree of long-range order that characterizes each step of the synthesis and is
      rarely observed for surface organic frameworks obtained via Ullmann coupling. 

PMID- 25582947
TI  - Distinguishing hypertension from hypertrophic cardiomyopathy as a cause of left
      ventricular hypertrophy.

PMID- 25582948
TI  - Electro-optical phenomena based on ionic liquids in an optofluidic waveguide.
AB  - An optofluidic waveguide with a simple two-terminal electrode geometry, when
      filled with an ionic liquid (IL), forms a lateral electric double-layer capacitor
      under a direct current (DC) electric field, which allows the realization of an
      extremely high carrier density in the vicinity of the electrode surface and
      terminals to modulate optical transmission at room temperature under low voltage
      operation (0 to 4 V). The unique electro-optical phenomenon of ILs was
      investigated at three wavelengths (663, 1330 and 1530 nm) using two waveguide
      geometries. Strong electro-optical modulations with different efficiencies were
      observed at the two near-infrared (NIR) wavelengths, while no detectable
      modulation was observed at 663 nm. The first waveguide geometry was used to
      investigate the position-dependent modulation along the waveguide; the strongest
      modulation was observed in the vicinity of the electrode terminal. The modulation
      phase is associated with the applied voltage polarity, which increases in the
      vicinity of the negative electrode and decreases at the positive electrode. The
      second waveguide geometry was used to improve the modulation efficiency.
      Meanwhile, the electro-optical modulations of seven ILs were compared at an
      applied voltage ranging from +/-2 V to +/-3.5 V. The results reveal that the
      modulation amplitude and response speed increase with increasing applied voltage,
      as well as the electrical conductivity of ILs. Despite the fact that the response
      speed isn't fast due to the high ionic density of ILs, the modulation amplitude
      can reach up to 6.0 dB when a higher voltage (U = +/-3.5 V) is applied for the IL
      [Emim][BF4]. Finally, the physical explanation of the phenomenon was discussed.
      The effect of the change in IL structure on the electro-optical phenomena was
      investigated in another new experiment. The results reveal that the electro
      optical phenomenon is probably caused mainly by the change in carrier
      concentration (ion redistribution near charged electrodes), which induces the
      enhancement and suppression of NIR optical absorption (contributed by C-H and N-H
      groups) in the vicinity of the negative electrode and positive electrode,
      respectively. 

PMID- 25582949
TI  - Identification of antibacterial and antioxidant constituents of the essential
      oils of Cynanchum chinense and Ligustrum compactum.
AB  - The aim of this research was to determine the chemical composition, antioxidant
      and antibacterial properties of the essential oils from Cynanchum chinense and
      Ligustrum compactum and isolation of antioxidant and antibacterial constituents
      from the essential oils. Thirty-eight components were identified in essential
      oils. Based on bioactivity-guided fractionation, guaiacol, linalool and 2
      phenylethanol were isolated and identified as active constituents. Both L.
      compactum flower oil and 2-phenylethanol showed high antibacterial performance,
      with inhibition zone from 22.8 +/- 0.8 to 11.9 +/- 2.0 mm at highest
      concentration, and minimum inhibitory concentration values ranging from 0.25% to
      1%. In both DPPH and ABTS assay, the active constituent guaiacol (IC50 = 4.15 +/-
      0.72 and 9.12 +/- 0.98 MUg mL(-1), respectively) exhibited high antioxidant
      activity, and the oils showed moderate antioxidant activity. These results
      indicate potential efficacy of active constituents and essential oils of L.
      compactum and C. chinense to control food-borne pathogenic and spoilage bacteria.

PMID- 25582950
TI  - Molecular effects of cancer-associated somatic mutations on the structural and
      target recognition properties of Keap1.
AB  - Kelch-like ECH-associated protein 1 (Keap1) plays an important regulatory role in
      the nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent oxidative stress
      response pathway. It functions as a repressor of Nrf2, a key transcription factor
      that initiates the expression of cytoprotective enzymes during oxidative stress
      to protect cells from damage caused by reactive oxygen species. Recent studies
      show that mutations of Keap1 can lead to aberrant activation of the antioxidant
      pathway, which is associated with different types of cancers. To gain a
      mechanistic understanding of the links between Keap1 mutations and cancer
      pathogenesis, we have investigated the molecular effects of a series of mutations
      (G333C, G350S, G364C, G379D, R413L, R415G, A427V, G430C and G476R) on the
      structural and target recognition properties of Keap1 by using nuclear magnetic
      resonance (NMR) spectroscopy, circular dichroism (CD) and isothermal titration
      calorimetry (ITC). Depending on their locations in the protein, these mutations
      are found to exert differential effects on the protein stability and target
      binding. Together with the proposed hinge-and-latch mechanism of Nrf2-Keap1
      binding in the literature, our results provide important insight into the
      molecular affect of different somatic mutations on Keap1's function as an Nrf2
      repressor. 

PMID- 25582951
TI  - Modulation of the kinetics of 3beta-hydroxy-5-oxo-5,6-secocholestan-6
      al/phosphatidylethanolamine Schiff base formation by cholesterol and cholesterol
      crystallization.
AB  - We have previously shown that the oxidized cholesterol 3beta-hydroxy-5-oxo-5,6
      secocholestan-6-al (atheronal A) reacts covalently with the free amino group of
      phosphatidylethanolamine (PE) or phosphatidylserine (PS) to produce a Schiff
      base. Accompanying this interaction, the biophysical properties of the
      phospholipid membranes are also changed. In the present report, we extend our
      earlier study of the rate of Schiff base formation in dimyristoyl PE/atheronal A
      binary mixtures to the more biologically relevant case in which varying amounts
      of cholesterol are also present. Using optical spectroscopy to monitor reaction
      kinetics, we demonstrate that the presence of cholesterol reduces the
      accessibility of the aldehyde moiety of the atheronal A to the free headgroup
      amine. We also find that the presence of atheronal A promotes the early onset of
      cholesterol crystallization in the ternary mixtures, perhaps with the Schiff base
      serving as a site for heterogeneous nucleation. 

PMID- 25582952
TI  - Label-free imaging and spectroscopic analysis of intracellular bacterial
      infections.
AB  - Staphylococcus aureus is one of the most frequent human pathogens that can also
      act as a facultative intracellular pathogen causing infections that are extremely
      difficult to treat. Only little is known about the pathogen's intracellular
      adaptation strategies to escape the host's response. Here, we present an advanced
      Raman-based imaging approach providing high quality false-color images to
      specifically identify intracellular S. aureus and to localize them exactly in
      three dimensions within endothelial cells. At the same time unprecedented
      insights into the metabolic characteristics of the pathogen are provided in a
      label-free and nondestructive manner. The spectral information reveals that the
      intracellular bacteria are in the exponential growth phase with a reduced
      replication rate and biochemically different from extracellular bacteria proving
      their adaptation to the host's conditions. This powerful biophotonic analysis
      tool paves the way for further mechanistic studies of difficult-to-investigate
      infection processes. 

PMID- 25582953
TI  - Life-stage-specific physiology defines invasion extent of a riverine fish.
AB  - Many ecologists have called for mechanism-based investigations to identify the
      underlying controls on species distributions. Understanding these controls can be
      especially useful to construct robust predictions of how a species range may
      change in response to climate change or the extent to which a non-native species
      may spread in novel environments. Here, we link spatially intensive observations
      with mechanistic models to illustrate how physiology determines the upstream
      extent of the aquatic ectotherm smallmouth bass (Micropterus dolomieu) in two
      headwater rivers. Our results demonstrate that as temperatures become
      increasingly cold across a downstream to upstream gradient, food consumption in
      age 0 bass becomes increasingly constrained, and as a result, these fish become
      growth limited. Sufficient first summer growth of age 0 bass is essential for
      overwinter survival because young bass must persist from energy reserves
      accumulated during the summer, and those reserves are determined by body size.
      Our field data reveal the upstream extent of adult bass reproduction corresponds
      to a point in the downstream/upstream gradient where cold temperatures impair
      growth opportunities in young bass. This pattern was repeated in both study
      streams and explained why bass positioned nests twice as far upstream in the warm
      compared to the cold stream in the same basin. Placement of spawning nests by
      adult bass is likely subject to strong evolutionary selection in temperate
      systems: if bass spawn too far upstream, their young are unlikely to grow large
      enough to survive the winter. Consumption and growth in older bass (age 3-4) was
      far less sensitive to temperature. Based on these data, we suggest that
      temperature-sensitive age 0 bass constrain the upstream distribution limits of
      bass within temperate streams. In this study, we investigated how temperature
      dependent physiology changed through the life history of a species and, in doing
      so, identified a climate-sensitive life-history stage that likely sets the
      distributional limits of all other life-history stages. We anticipate the
      framework developed here could be employed to identify how similar stage-specific
      environmental sensitivity determines distribution in many other ectothermic
      species. 

PMID- 25582957
TI  - Electrical dysfunction associated with conductor externalization of a silicone
      left ventricular lead.
AB  - The St. Jude Medical QuickFlex LV lead family (St. Jude Medical, Inc., St. Paul,
      MN, USA) has been placed under advisory by the manufacturer due to a reported
      small number of cases of outer insulation failure and conductor externalization.
      There have been no reports of alteration of any electrical parameters associated
      with externalization. In this report, a sudden drop of impedance and rise in
      capture threshold of the left ventricular ring electrode is described, associated
      with the corresponding externalization of the inner conductor cables confirmed on
      physical examination. Flexion or torsion of lead was demonstrative of forces
      favoring externalization of inner conductor cables. Saline bath testing revealed
      a reproducible, transient reduction in lead resistance associated with conductor
      externalization. Close monitoring of electrical performance of this lead family
      is indicated. 

PMID- 25582954
TI  - No DNA damage response and negligible genome-wide transcriptional changes in
      human embryonic stem cells exposed to terahertz radiation.
AB  - Terahertz (THz) radiation was proposed recently for use in various applications,
      including medical imaging and security scanners. However, there are concerns
      regarding the possible biological effects of non-ionising electromagnetic
      radiation in the THz range on cells. Human embryonic stem cells (hESCs) are
      extremely sensitive to environmental stimuli, and we therefore utilised this cell
      model to investigate the non-thermal effects of THz irradiation. We studied DNA
      damage and transcriptome responses in hESCs exposed to narrow-band THz radiation
      (2.3 THz) under strict temperature control. The transcription of approximately 1%
      of genes was subtly increased following THz irradiation. Functional annotation
      enrichment analysis of differentially expressed genes revealed 15 functional
      classes, which were mostly related to mitochondria. Terahertz irradiation did not
      induce the formation of gammaH2AX foci or structural chromosomal aberrations in
      hESCs. We did not observe any effect on the mitotic index or morphology of the
      hESCs following THz exposure. 

PMID- 25582955
TI  - The age factor for mitoxantrone's cardiotoxicity: multiple doses render the adult
      mouse heart more susceptible to injury.
AB  - Age is a known susceptibility factor for the cardiotoxicity of several anticancer
      drugs, including mitoxantrone (MTX). The impact of anticancer drugs in young
      patients is underestimated, thus we aimed to evaluate the cardiotoxicity of MTX
      in juvenile and adult animals. Juvenile (3 week-old) and adult (8-10 week-old)
      male CD-1 mice were used. Each group was treated with a 9.0mg/kg cumulative dose
      of MTX or saline; they were maintained in a drug-free period for 3-weeks after
      the last administration to allow the development of late toxicity (protocol 1),
      or sacrificed 24h after the last MTX administration to evaluate early
      cardiotoxicity (protocol 2). In protocol 1, no adult mice survived, while 2 of
      the juveniles reached the end of the protocol. High plasma aspartate
      aminotransferase/alanine aminotransferase ratio and a high cardiac
      reduced/oxidized glutathione ratio were found in the surviving MTX-treated
      juvenile mice. In protocol 2, a significant decrease in plasma creatine-kinase MB
      in juveniles was found 24h after the last MTX-administration. Cardiac histology
      showed that both MTX-treated populations had significant damage, although higher
      in adults. However, MTX-treated juveniles had a significant increase in fibrotic
      tissue. The MTX-treated adults had higher values of cardiac GSSG and protein
      carbonylation, but lower cardiac noradrenaline levels. For the first time, mature
      adult animals were shown to be more susceptible to MTX as evidenced by several
      biomarkers, while young animals appear to better adjust to the MTX-induced
      cardiac injury. Even so, the higher level of fibrotic tissue and the histological
      damage showed that MTX also causes cardiac damage in the juvenile population. 

PMID- 25582958
TI  - Purification, immobilization, and biochemical characterization of l-arginine
      deiminase from thermophilic Aspergillus fumigatus KJ434941: anticancer activity
      in vitro.
AB  - l-Arginine deiminase (ADI) has a powerful anticancer activity against various
      tumors, via arginine depletion, arresting the cell cycle at G1 phase. However,
      the current clinically tried bacterial ADI displayed a higher antigenicity and
      lower thermal stability. Thus, our objective was to purify and characterize this
      enzyme from thermophilic fungi, to explore its catalytic and antigenic properties
      for therapeutic uses. ADI was purified from thermophilic Aspergillus fumigatus
      KJ434941 to its electrophoretic homogeneity by 5.1-fold, with molecular subunit
      50 kDa. The purified ADI was PEGylated and covalently immobilized on dextran to
      explore its catalytic properties. The specific activity of free ADI, PEG-ADI, and
      Dex-ADI was 26.7, 21.5, and 18.0 U/mg, respectively. At 50 degrees C, PEG-ADI
      displays twofold resistance to thermal denaturation (t1/2 13.9 h), than free ADI
      (t1/2 6.9 h), while at 70 degrees C, the thermal stability of PEG-ADI was
      increased by 1.7-fold, with similar stability to Dex-ADI with the free one.
      Kinetically, free ADI had the higher catalytic affinity to arginine, followed by
      PEG-ADI and Dex-ADI. Upon proteolysis for 30 min, the residual activity of native
      ADI, PEG-ADI, and Dex-AD was 8.0, 32.0, and 20.0% for proteinase K and 10.0,
      52.0, and 90.0% for acid protease, respectively. The anticancer activity of the
      ADIs was assessed against HCT, HEP-G2, and MCF7, in vitro. The free and PEG-ADI
      exhibits a similar cytotoxic efficacy for the tested cells, lower than Dex-ADI.
      The free ADI had IC50 value 22.0, 16.6, and 13.9 U/mL, while Dex-ADI had 3.98,
      5.18, and 4.43 U/mL for HCT, MCF7, and HEPG-2, respectively. The in vitro
      anticancer activity of ADI against HCT, MCF7, and HEPG-2 was increased by five-,
      three-, and threefold upon covalent modification by dextran. The biochemical and
      hematological parameters of the experimented animals were not affected by ADIs
      dosing, with no signs of anti-ADI immunoglobulins in vivo. The in vivo half-life
      time of free ADI, PEG-ADI, and Dex-ADI was 29.7, 91.1, 59.6 h, respectively. The
      present findings explored a novel thermostable, less antigenic ADI from
      thermophilic A. fumigatus, with further molecular and crystallographic analyses,
      this enzyme will be a powerful candidate for clinical trials.

PMID- 25582959
TI  - The impact of making-weight on cognitive performance in apprentice jockeys.
AB  - Jockeys regularly engage in rapid weight-loss practices in preparation for
      competition. These practices are thought to impair cognitive function, although
      the evidence in support of this theory remains inconclusive. The purpose of this
      study was to examine the effects of making-weight on cognitive function in
      apprentice jockeys in a simulated and competitive environment. Apprentice jockeys
      (n = 12) reduced their body mass by 4% in 48 h in a simulated environment using
      weight-loss methods typically adopted in preparation for racing. Simple and
      choice reaction time, attention, learning and memory were assessed before and
      after the weight loss. A further 10 apprentice jockeys performed the cognitive
      function assessment in a competitive racing environment at both a self-reported
      "normal" and "light" body mass. Hydration status and body mass were assessed in
      all trials. In the simulated environment, body mass was reduced by 4.2 +/- 0.3%,
      yet no change in cognitive function was observed. Cognitive function also
      remained unchanged in the competitive environment after a body mass loss of 5.7
      +/- 1.9%. Typical reductions in body mass in preparation for racing have no
      effect on cognitive function in apprentice jockeys in a simulated and competitive
      environment. Further research is required to investigate the physiological
      mechanisms preventing the adverse effects of making-weight on cognitive function
      in jockeys.

PMID- 25582960
TI  - A pilot study of proximal strength training in Charcot-Marie-Tooth disease.
AB  - Gait analysis of people with Charcot-Marie-Tooth (CMT) disease revealed proximal
      adaptive gait strategies to compensate for foot drop. We previously demonstrated
      that hip flexor muscle fatigue can limit walking endurance. This pilot study used
      a single-blinded cross over design to investigate the effect of a 16-week home
      based programme of resistance training on hip flexor muscle strength. Measures of
      walking endurance, gait speed, exertion, fatigue, and general activity were also
      recorded. The exercise protocol was based on American College of Sports Medicine
      recommendations. A mixed effects model was used for analysis. Twenty-six people
      finished the study, with average reported exercise participation of 93%. No
      negative effects of exercise were observed. Significant increase in hip flexor
      muscle strength was observed on the left, but not the right. No changes were
      observed in walking speed and endurance measures. This pilot study of home-based
      resistance training showed a modest improvement in hip strength but only on one
      side. The lack of a more significant improvement and no improvement in walking
      measures suggests that this training protocol may not be optimal for people with
      CMT and that patients may need to stratified differently for training studies in
      CMT. 

PMID- 25582961
TI  - Laparoscopic approach to mucocele of appendiceal mucinous cystadenoma:
      feasibility and short-term outcomes in 24 consecutive cases.
AB  - BACKGROUND: Mucocele of the appendix is an uncommon condition where luminal
      distention by mucin is usually attributable to a mucinous cystadenoma. From a
      surgical standpoint, it is critical that the mucin-filled tumor remains intact
      during resection. Spillage of mucin into peritoneal cavity may otherwise lead to
      pseudomyxoma peritonei. Although acute appendicitis is managed successfully by
      laparoscopic appendectomy, the potential for rupture has fueled concerns over
      laparoscopic resection of appendiceal mucoceles. Our aim was to evaluate
      feasibility, safety, and short-term outcomes of laparoscopic resection in
      patients with a mucocele of appendix secondary to mucinous cystadenoma. METHODS:
      Data collected prospectively at the Department of Surgery from October 2005 to
      December 2013 were reviewed, selecting all instances of preoperatively identified
      appendiceal mucoceles, which was confirmed as mucinous cystadenomas by histology
      after elective laparoscopic surgery. Patient demographics, surgical data
      (operative procedures and times, intraoperative complications), and short-term
      postoperative outcomes were analyzed retrospectively. RESULTS: Twenty-four
      consecutive patients (female 14) were studied. Mean age was 60.0 years (range 42
      81 years). Surgical procedures included simple appendectomy (1/24, 4.2 %),
      partial cecectomy (15/24, 62.5 %), and ileocecal resection (8/24, 33.3 %). Mean
      operative time was 108.5 min (range 40-205 min). No intraoperative spillage of
      mucin occurred due to inadvertent rupture of tumor. Resection margins uniformly
      were negative for tumor. Mean maximal length and diameter of tumors were 7.9 cm
      (range 3.0-20.0 cm) and 3.2 cm (range 1.0-7.5 cm), respectively. One patient (4.2
      %) suffered postoperative morbidity (wound infection). CONCLUSIONS: A
      laparoscopic approach proved feasible and safe for surgical management of
      appendiceal mucocele due to mucinous cystadenoma. However, long-term follow-up is
      warranted for more conclusive support.

PMID- 25582962
TI  - Inattention blindness in surgery.
AB  - BACKGROUND: Inattention blindness (IB) can be defined as the failure to perceive
      an unexpected object when attention is focussed on another object or task. The
      principal aim of this study was to determine the effect of cognitive load and
      surgical image guidance on operative IB. METHODS: Using a randomised control
      study design, participants were allocated to a high or low cognitive load group
      and subsequently to one of three augmented reality (AR) image guidance groups (no
      guidance, wireframe overlay and solid overlay). Randomised participants watched a
      segment of video from a robotic partial nephrectomy. Those in the high cognitive
      load groups were asked to keep a count of instrument movements, while those in
      the low cognitive load groups were only asked to watch the video. Two foreign
      bodies were visible within the operative scene: a swab, within the periphery of
      vision; and a suture, in the centre of the operative scene. Once the participants
      had finished watching the video, they were asked to report whether they had
      observed a swab or suture. RESULTS: The overall level of prompted inattention
      blindness was 74 and 10 % for the swab and suture, respectively. Significantly
      higher levels of IB for the swab were seen in the high versus the low cognitive
      load groups, but not for the suture (8 vs. 47 %, p < 0.001 and 90 vs. 91 %, p =
      1.000, for swab and suture, respectively). No significant difference was seen
      between image guidance groups for attention of the swab or suture (29 vs. 20 %, p
      = 0.520 and 22 vs. 22 %, p = 1.000, respectively). CONCLUSIONS: The overall
      effect of IB on operative practice appeared to be significant, within the context
      of this study. When examining for the effects of AR image guidance and cognitive
      load on IB, only the latter was found to have significance.

PMID- 25582963
TI  - Total laparoscopic management of lesions involving liver segment 7.
AB  - BACKGROUND: Until recently, laparoscopic resection of tumors involving segment 7
      (s7) of the liver was seen as a relative contraindication. We analyzed our
      experiences with laparoscopic resection of tumors in s7. METHODS: Retrospective
      analysis of prospective database on operative and postoperative characteristics
      and surgical outcomes of patients in whom the intention was to remove tumors
      located in s7 of the liver laparoscopically. We defined two groups: those with
      laparoscopic metastasectomy of s7 (s7 group) and those undergoing laparoscopic
      right posterior sectionectomy (RPS group). RESULTS: Of 400 patients undergoing
      laparoscopic liver resection, 20 patients (5 %) underwent total laparoscopic
      resections of tumors in s7 (7 metastasectomy of s7 and 13 RPS). The type of
      resection was decided on the basis of tumor size and location. Median age was 70
      years (range 46-82), and the indication for surgery was mainly CRLM (n = 13, 65
      %) and HCC (n = 4, 20 %). There was 1 (5 %) conversion. Mean operative times were
      252 min (+/-69) for s7 and 271 min (+/-102) for RPS. The mean intraoperative
      blood loss was 400 mL (+/-493) for s7 and 625 mL (+/-363) for RPS. A Pringle
      maneuver was used in 86 % of patients in s7 group and 75 % of patients in RPS
      group. Mean total hospital stay was 4.6 days (+/-2.5) in s7 and 6.9 days (+/-7.8)
      for RPS. The overall R0 resection rate was 95 % (s7 100 %, RPS 92 %). CONCLUSION:
      Although resection of lesions in s7 is technically demanding, a laparoscopic
      approach can be performed safely and effectively in experienced hands.

PMID- 25582964
TI  - Comparison of the major postoperative complications between laparoscopic distal
      and total gastrectomies for gastric cancer using Clavien-Dindo classification.
AB  - BACKGROUND: Laparoscopy-assisted total gastrectomy (LATG) has not been as popular
      as laparoscopy-assisted distal gastrectomy (LADG) because of its undetermined
      safety and postoperative complications compared with LADG. Therefore, LATG
      requires further study. PATIENTS AND METHODS: A total of 663 patients who
      underwent LADG or LATG for gastric cancer in a single institution from April 2004
      to April 2014 were included. The clinicopathologic characteristics and risk
      factors related to major complications (Clavien-Dindo grade >= IIIa) were
      analyzed between the LADG (n = 569) and LATG groups (n = 94). RESULTS: The
      incidence of major postoperative complications was significantly higher for LATG
      (LADG vs. LATG: 8.1 vs. 18.1 %, P = 0.002). Although postoperative bleeding was
      not different between the groups (3.2 vs. 3.2 %, P = 0.991), the incidence of
      bowel leakage was significantly higher for LATG (2.6 vs. 6.8 %, P = 0.028).
      Leakage from the anastomosis site was more frequent following LATG (5.3 %)
      compared with LADG (0.5 %) (P < 0.001). Leakage from the duodenal stump tended to
      be more frequent, though not significant, for LADG (2.0 vs. 1.1 %, P = 0.602).
      Advanced gastric cancer, LATG, and longer operation time were significant factors
      that affected the incidence of postoperative complications in a univariate
      analysis. In multivariate analysis, there were no independent risk factors, but
      LATG was nearly a significant, independent risk factor (odds ratio 1.89; 95 % CI
      0.965-3.71, P = 0.063). CONCLUSION: More major complications were observed for
      LATG, particularly with esophagojejunostomy. These results show that LATG is more
      invasive than LADG in terms of the postoperative morbidity. More caution and
      experience are needed when performing LATG.

PMID- 25582965
TI  - New isolated bovine colon model dedicated to colonic ESD hands-on training:
      development and first evaluation.
AB  - INTRODUCTION: ESD is the reference method to achieve en bloc resections for large
      digestive lesions. Nevertheless, it is a difficult and risky technique. Animal
      models exist to teach the initial skills, particularly in Japan, where pigs'
      stomachs are dedicated models to gastric ESD. In Europe, we have to develop
      different strategies of teaching with dedicated colon models. A pig colon is a
      good model but thinner and narrower than a human's. In this present work, we
      evaluated a bovine colon model to perform rectal ESD in retroflexion. METHODS:
      First, we prepared six bowels to precise the preparation protocol. Then, two
      endoscopists unexperienced in ESD performed 64 procedures on eight models.
      Learning curves and factors of variation were studied. RESULTS: A precise
      protocol to prepare the colon was defined. The two students achieved en bloc
      resection in 89.1 % of cases with a rate of 6.2 % of perforations. A large
      heterogeneity appeared between the speed and the success rate depending mainly on
      the age of the animal bowel. Using calf colons, the failure rates were higher (p
      = 0.002) and the speed was lower (p < 0.001) than for adult bovine ones. A
      learning curve appeared with, respectively, 0.49 and 0.59 cm(2)/min throughout
      the study. No significant difference appeared between measured and calculated
      specimen areas. DISCUSSION: Bovine colon is a new model to teach ESD in
      colorectal conditions. The bovine age is important to homogenize the model. A
      learning curve existed with a time procedure decreasing throughout the study.
      Further studies are needed to evaluate the precise learning curve with more
      students. CONCLUSION: A bovine colon model is a suitable model to teach
      colorectal ESD. Nevertheless, an adult bovine colon model is more homogeneous
      than a calf one.

PMID- 25582967
TI  - Metacognition and general functioning in patients with schizophrenia and a
      history of criminal behavior.
AB  - Metacognitive difficulties have been linked to social dysfunction in
      schizophrenia. However, research examining the role of metacognition in the
      social functioning of patients with a history of violence and criminality is very
      limited. This research is especially important for this group given their
      relatively poor prognosis and their risk to reoffend, as well as the promising
      benefits of integrating metacognitive approaches in psychosocial treatments. In
      this study, the association between metacognition and global social functioning
      was examined in 79 patients with schizophrenia with a criminal background. We
      also examined the association of positive, negative and disorganized symptoms
      with social functioning and the extent to which metacognition mediates this
      association. The results indicate that poor social functioning is associated with
      metacognitive difficulties and higher levels of delusions and Conceptual
      Disorganization. In addition, meditation analyses showed that metacognition
      accounted for about 11% of the total effect size of the association between
      delusions and social dysfunction, suggesting that the relationship between
      delusions and social dysfunction is partially driven by impaired metacognition.
      These findings underscore the importance of interventions designed to enhance the
      patients' metacognitive capacities, that is, the more proximal capacities linked
      to poorer social functioning. 

PMID- 25582966
TI  - Redesigning emergency patient flow with timely quality care at the Alfred.
AB  - OBJECTIVES: The 4 h National Emergency Access Target was introduced in 2011. The
      Alfred Hospital in Melbourne implemented a hospital-wide clinical service
      framework, Timely Quality Care (TQC), to enhance patient experience and care
      quality by improving timeliness of interventions and investigations through the
      emergency episode and admission to discharge in 2012. We evaluated TQC's effect
      on achieving the National Emergency Access Target and associated safety and
      quality indicators. METHODS: Retrospective analysis with piecewise regression of
      215 125 ED attendances before/after implementation, November 2009 to August 2013;
      with comparison of proportions of patients discharged, admitted or transferred
      from ED within 4 h of arrival; left at risk; unplanned ED re-attendances up to 28
      days; ED length of stay; and in-hospital mortality. RESULTS: The percentage of
      patients admitted, discharged or transferred within 4 h rose from 60% in 2010, to
      74% in 2013. Median ED length of stay decreased significantly. Rate of unplanned
      ED re-presentations decreased by 27%, 22% and 17% within 24 h, 48 h and 7 days,
      respectively; and patient numbers leaving at risk halved from 8% to 4%. Mortality
      for admitted patients declined from 3.5% to 2.2%. All results were statistically
      significant. CONCLUSIONS AND FUTURE DIRECTIONS: TQC resulted in improvement in
      timeliness of care for emergency patients without compromising safety and
      quality. Success is attributed to effective engagement of stakeholders with a
      hospital-wide approach to redesigning the care pathway and establishing a new set
      of principles that underpin care from the time of ED arrival.

PMID- 25582969
TI  - Correction.
AB  - [This corrects the article DOI: 10.1136/bmjresp-2014-000040.]. 

PMID- 25582968
TI  - Coping styles: longitudinal development from ages 17 to 33 and associations with
      psychiatric disorders.
AB  - Relationships of coping styles to maturation, sex, and psychiatric diagnoses are
      not well defined. Accordingly, we examined their development from late
      adolescence into adulthood, and their associations with psychiatric disorders. We
      assessed coping styles in 970 subjects prospectively, at mean ages 17, 24, 29,
      and 33, using the Coping Inventory for Stressful Situations. Selected DSM-IV-TR
      lifetime psychiatric disorders were assessed at age 24. We found that reliance on
      adaptive task-oriented coping (TOC) increased sharply from ages 17 to 24, (effect
      size [ES]=0.94), and stabilized thereafter; less adaptive emotion-oriented coping
      (EOC) declined continuously over time. Men and women had similar TOC scores from
      ages 17 to 33, but women had moderately higher EOC scores at age 17 (ES=0.53).
      Greater reliance on EOC at age 24 was associated with more major depressive or
      anxiety disorders, adjusted for stressors and sex. Greater use of TOC at age 17
      was associated with less risk for drug or alcohol abuse/dependence by age 24
      after adjusting for sex and stressors. In conclusion, coping styles generally
      became more adaptive with maturation, though women used EOC more than men.
      Additionally, greater reliance on TOC in late-adolescence may reduce risks for
      substance use disorders. 

PMID- 25582970
TI  - [Conservative treatment of cervical radiculopathy with 5% lidocaine medicated
      plaster].
AB  - AIM: Cervical radiculopathy is a mixed pain syndrome characterized by
      neuropathic, skeletal and myofascial pain. This condition is frequently found in
      developed countries and is a significant source of disability and a reason for
      frequent medical consultation. In our Pain Therapy Centre, cervical radiculopathy
      is initially treated with bi-weekly cycles of mesotherapy coupled, at least 15
      days later, with physiotherapy to reach the complete mobilization of cervical
      spine. Cervical radiculopathy is a localized neuro-pathic pain and in agreement
      with international guidelines, we checked if patients treated topically with 5%
      lidocaine medicated plaster may benefit in improving pain management and in
      reducing the time necessary to start physiotherapy. METHODS: A retrospective
      study was carried out on 60 patients, of which 30 were treated with mesotherapy
      and 30 were treated with 5% lidocaine medicated plaster. Data for a total of 30
      days observation were collected from the patient medical records. In particular,
      besides medical history, intensity of pain, intensity of allodynia and pain were
      considered. RESULTS AND CONCLUSION: For all analyzed parameters, both treatments
      were effective, but patients treated with 5% lidocaine medicated plaster showed
      faster control of the painful symptoms, an essential condition for an earlier
      rehabilitative treatment.

PMID- 25582971
TI  - Suicidality, self-harm and psychotic-like symptoms in a general adolescent
      psychiatric sample.
AB  - AIM: We investigated the associations between clinical high-risk for psychosis
      (CHR), psychotic-like symptoms and suicidality among adolescent psychiatric
      patients. METHODS: The sample consisted of 54 CHR and 107 non-CHR psychiatric
      patients aged 15-18 in Helsinki, Finland, who were assessed at the beginning of
      their psychiatric treatment with the Structured Interview for Prodromal Syndromes
      (SIPS). Current suicidality was measured with the Beck Depression Inventory (item
      9), while lifetime suicidality was evaluated from all available data, including
      patient files. The participants were followed for 2.8-8.9 years via the national
      hospital discharge register, with the follow-up outcome being intentional self
      harm. Data on suicides were also gathered from the Causes of Death statistics.
      RESULTS: Only 30.5% of the adolescents had no suicidal ideation at the beginning
      of their treatment. CHR risk state and SIPS-assessed delusions, suspiciousness,
      and hallucinations were associated with higher current suicidality. Of the 154
      adolescents with register follow-up, there were five (3.2%) with intentional self
      harm resulting in hospital treatment, all female. CHR status was not associated
      with self-harm. Current suicidality, familial risk of psychosis, and SIPS
      decreased expression of emotions were associated with self-harm during follow-up.
      In a Cox regression analysis model among girls, only decreased expression of
      emotions remained a significant predictor of intentional self-harm. Baseline
      suicidality measures were not associated with transitions to psychosis.
      CONCLUSIONS: CHR status was associated with higher current suicidality but did
      not predict follow-up intentional self-harm in treatment-seeking adolescents.
      Decreased expression of emotions may indicate higher risk of intentional self
      harm in adolescent treatment-seeking girls.

PMID- 25582972
TI  - Information and knowledge about Down syndrome among women and partners after
      first trimester combined testing.
AB  - We assessed reasons among women and partners for choosing combined ultrasound
      biochemistry testing, information and knowledge about Down syndrome and decisions
      concerning invasive procedures and termination of pregnancy in a prospective
      cohort study in Uppsala County. In all 105 pregnant women and 104 partners coming
      for a combined ultrasound-biochemistry test answered a questionnaire. The most
      common reason for a combined ultrasound-biochemistry test was "to perform all
      tests possible to make sure the baby is healthy". Internet and midwives were the
      most common sources of information. Seventy-two percent had not received
      information on what it means to live with a child with Down syndrome. Many
      expectant parents perceived information as insufficient. Both women and partners
      had varying or low levels of knowledge about medical, cognitive and social
      consequences of Down syndrome. Twenty-five percent had not decided on an invasive
      test if indicated and only 42% would consider termination of pregnancy with a
      Down syndrome diagnosis. 

PMID- 25582973
TI  - Relationship between performance barriers and pharmacist competency towards the
      implementation of an expanded public health pharmacy role.
AB  - OBJECTIVE: The objective of this study was to examine the relationship between
      performance barriers and competency, and implementation of an expanded public
      health role for community pharmacists. METHODS: A validated questionnaire was
      utilised for this study whereby three variables of the study (performance
      barriers, competency and public health role) were measured using a 5-point Likert
      scale. Three hundred questionnaires were distributed to target respondents of
      registered community pharmacies in five states (Johor, Negeri Sembilan, Selangor,
      Perak and Penang) in Malaysia. The data were analysed utilising the principles of
      structural equation modelling. KEY FINDINGS: There were 191 completed and usable
      responses received, which represented a 66.7% response rate. This study showed
      perceived competency had a direct relationship with delivering a general public
      health role. A perceived lack of competency was shown to be a barrier to
      fulfilling a public health role. However, other factors, such as design of
      premises, IT infrastructure and pay, were not viewed as barriers to carrying out
      a public health role. CONCLUSION: Perceived competency is an obstacle for
      community pharmacists to undertake a public health role in Malaysia. Adequate
      training programmes in pharmaceutical public health have to be put in place to
      address this concern and this should therefore be a priority.

PMID- 25582974
TI  - Longitudinal analysis of endurance and respiratory function from a natural
      history study of Morquio A syndrome.
AB  - OBJECTIVES: Baseline data from the Morquio A Clinical Assessment Program (MorCAP)
      revealed that individuals with Morquio A syndrome show substantial impairment in
      multiple domains including endurance and respiratory function (Harmatz et al.,
      Mol Genet Metab, 2013). Here, 1- and 2-year longitudinal endurance and
      respiratory function data are presented. METHODS: Endurance was assessed using
      the 6-minute walk test (6MWT) and the 3-minute stair climb test (3MSCT).
      Respiratory function was evaluated by measuring forced vital capacity (FVC) and
      maximum voluntary ventilation (MVV). Data were analyzed using repeated measures
      ANCOVA models. Annualized estimates of change were determined using model
      estimates and interpolation. RESULTS: 353, 184, and 78 subjects were assessed at
      Year 0 (baseline), Year 1, and Year 2, respectively. The overall annualized
      estimate of change (SE) in 6MWT distance was -4.86+/-3.25m; a larger decline of 
      6.84+/-5.38m was observed in the subset of subjects meeting the
      inclusion/exclusion criteria of the Phase 3 clinical trial of elosulfase alfa
      (>=5years of age with baseline 6MWT distance >=30 and <=325m). In contrast,
      little change (-0.14+/-0.60stairs/min) was observed in 3MSCT. Annualized changes
      (SE) in FVC and MVV were 2.44+/-0.68% and 1.01+/-2.38%, respectively. FVC and MVV
      increased in patients aged <=14years, but decreased in older patients.
      CONCLUSIONS: The natural history of Morquio A syndrome is characterized by
      progressive impairment of endurance as measured by the 6MWT. Longitudinal trends
      in FVC and MVV showing increase in younger patients, but decrease in older
      patients, are likely to be influenced by growth. Changes in 6MWT may represent a
      sensitive measure of disease progression in ambulatory Morquio A patients.

PMID- 25582975
TI  - Risk factors for HIV and STI diagnosis in a community-based HIV/STI testing and
      counselling site for men having sex with men (MSM) in a large German city in 2011
      2012.
AB  - BACKGROUND: In recent years community-based voluntary counselling and testing
      sites (CB-VCT) for men having sex with men (MSM) have been established in larger
      cities in Germany to offer more opportunities for HIV testing. Increasingly, CB
      VCTs also offer testing for other bacterial sexually transmitted infections. In
      Hamburg, tests in CB-VCTs are offered free and anonymously. Data on demographics
      and sexual risk behaviours are collected with a paper questionnaire. METHODS:
      Questionnaire data from the MSM CB-VCT in Hamburg were linked with serological
      test results for HIV and syphilis, and with rectal and pharyngeal swab results
      for gonorrhoea and chlamydia. MSM were defined as males reporting male sex
      partners. CB-VCT clients were characterized demographically, and associations
      between sexual behaviour variables and diagnosis of HIV and sexually transmitted
      infections (STI) were analysed by bivariate and multivariate logistic regression
      analysis. RESULTS: Among the male clients of the CB-VCT in 2011-2012 who were
      tested for HIV or any STI 1476 reported male sex partners. Unprotected anal
      intercourse (UAI) was reported as reason for testing by 61% of the clients. Forty
      one of 1413 clients testing for HIV were tested positive (2.9%). Twenty-four of
      1380 clients testing for syphilis required treatment (1.7%). Tests for
      simultaneous detection of N. gonorrhoea and Chlamydia trachomatis were conducted
      on 882 pharyngeal and 642 rectal swabs, revealing 58 (=6.6%) pharyngeal and 71
      (=11.1%) rectal infections with one or both pathogens. In multivariate logistic
      regression analysis number of partners, UAI (OR=2.42) and relying on visual
      impression when selecting sex partners (OR = 2.92) were associated with increased
      risks for diagnosis of syphilis or a rectal STI. Syphilis or rectal STI diagnosis
      (OR=4.52) were associated with increased risk for HIV diagnosis. CONCLUSIONS: The
      MSM CB-VCT in Hamburg reaches clients at high risk for HIV and STIs. The
      diagnosis of syphilis or a rectal STI was associated with increased odds of
      testing positive for HIV. Due to the high prevalence of curable bacterial STI
      among clients and because syphilis and rectal bacterial STI may facilitate HIV
      transmission, MSM asking for HIV tests in CB-VCTs should also be offered tests
      for other bacterial STIs.

PMID- 25582976
TI  - Associations between neuropsychiatric symptoms and cognition in Chinese
      idiopathic Parkinson's disease patients.
AB  - The associations between neuropsychiatric symptoms and cognition, frontal lobe
      function and frontal behavioral changes in the Chinese idiopathic Parkinson's
      disease (PD) population are largely unknown. This study included 348 idiopathic
      PD patients from southwest China. Neuropsychiatric symptoms were investigated
      using the Neuropsychiatric Inventory Questionnaire (NPI), and cognition was
      assessed using Addenbrooke's Cognitive Examination-Revised (ACE-R). The Frontal
      Assessment Battery (FAB) was used to evaluate frontal function and the Frontal
      Behavior Inventory (FBI) was used to assess frontal behavioral changes. The mean
      (+/- standard deviation) age of the PD patients was 60.24 +/- 12.07 years, and
      the mean disease duration was 3.88 +/- 3.34 years. The mean NPI score was 3.49 +/
      4.00. The mean score of ACE-R was 76.82 +/- 16.73. The mean score of FAB was
      15.27 +/- 2.90, and the mean score of FBI was 3.18 +/- 5.17. Weak negative
      correlations between the NPI and ACE-R scores as well as FAB score were found in
      the total sample, the male patient subgroup, the early onset PD subgroup and the
      late onset PD subgroup. Strong positive correlations were found between the NPI
      and FBI scores in the total sample (r=0.661, p<0.001), the male patient subgroup
      (r=0.789, p<0.001) and the late onset PD subgroup (r=0.749, p<0.001). Moderate
      positive correlations were found between the NPI and FBI scores in the female
      patient subgroup (r=0.536, p<0.001) and the early onset PD subgroup (r=0.462,
      p<0.001). Neuropsychiatric symptoms were closely associated with frontal
      behavioral changes but were not closely related with worse cognition and frontal
      lobe function in the Chinese idiopathic PD population.

PMID- 25582977
TI  - Fibril breaking accelerates alpha-synuclein fibrillization.
AB  - The formation of amyloid fibrils of alpha-synuclein (alphaSyn), the key protein
      in Parkinson's disease, is an autocatalytic process that is seeded by mature
      alphaSyn fibrils. Based on systematic measurements of the dependence of the
      fibril growth rate on the concentrations of monomers and preformed fibrillar
      seeds, we propose a mechanism of alphaSyn aggregation that includes monomer
      binding to fibril ends and secondary nucleation by fibril breaking. The model
      explains the increase of the alphaSyn aggregation rate under shaking conditions
      and the exponential increase in the fraction of fibrillar protein at the initial
      stages of alphaSyn aggregation. The proposed autocatalytic mechanism also
      accounts for the high variability in the aggregation lag time. The rate constant
      of monomer binding to the ends of fibrils, k+ ~ 1.3 mM(-1) s(-1), was estimated
      from the aggregation rate and previously reported average fibril lengths. From
      the aggregation rates at low concentrations the binding of monomeric alphaSyn to
      fibrils was found to be almost irreversible, with an equilibrium dissociation
      constant (Kd) smaller than 3 MUM. 

PMID- 25582978
TI  - Immunostaining of skin biopsy adds no diagnostic value in MGUS-associated
      peripheral neuropathy.
AB  - BACKGROUND AND PURPOSE: For several decades an association between MGUS, IgM-MGUS
      in particular, and peripheral neuropathy has been suspected. Several
      histopathology studies have shown binding of IgM to myelin and a secondary
      widening of myelin lamellae in cutaneous nerves and in the sural nerve of
      patients with IgM-MGUS, or Waldenstrom's Macroglobulinaemia (WM), and peripheral
      neuropathy. In this retrospective study we investigated the value of skin biopsy
      examination in the diagnosis of MGUS- and WM-associated peripheral neuropathy.
      METHODS: A total of 117 patients, who were examined for an M-component in serum
      with associated nerve symptoms, had a skin biopsy taken and examined for
      immunoglobulin deposition in cutaneous nerves. Thirty-five patients were
      diagnosed with MGUS or WM and peripheral neuropathy with no other cause of
      neuropathy. Nineteen patients had MGUS but no peripheral neuropathy. RESULTS: Of
      the 35 patients with MGUS or WM and peripheral neuropathy, four had
      immunoglobulin deposition in the skin biopsy, all of whom had an IgM gammopathy.
      In the control group of 19 without peripheral neuropathy, three had
      immunoglobulin deposition in the skin biopsy, all of whom had IgM-MGUS. In both
      groups, there was a trend towards higher IgM blood levels in patients with
      immunoglobulin deposition. Half of the patients with IgM gammopathy in the
      neuropathy group had anti-MAG reactivity, whereas only one in the control group
      had weak anti-MAG reactivity. CONCLUSION: Our study indicates that examination of
      skin biopsies for immunoglobulin deposition does not add significant diagnostic
      value in the evaluation of neuropathies suspected to be caused by MGUS or WM. IgM
      immunoglobulin deposition in skin biopsy might merely be an epiphenomenon
      secondary to high IgM blood levels.

PMID- 25582979
TI  - Computer use and carpal tunnel syndrome: A meta-analysis.
AB  - BACKGROUND: Studies have reported contradictory results on the role of keyboard
      or mouse use in carpal tunnel syndrome (CTS). This meta-analysis aimed to assess
      whether computer use causes CTS. METHODS: Literature searches were conducted in
      several databases until May 2014. Twelve studies qualified for a random-effects
      meta-analysis. Heterogeneity and publication bias were assessed. RESULTS: In a
      meta-analysis of six studies (N=4964) that compared computer workers with the
      general population or other occupational populations, computer/typewriter use
      (pooled odds ratio (OR)=0.72, 95% confidence interval (CI) 0.58-0.90),
      computer/typewriter use >=1 vs. <1h/day (OR=0.63, 95% CI 0.38-1.04) and
      computer/typewriter use >=4 vs. <4h/day (OR=0.68, 95% CI 0.54-0.87) were
      inversely associated with CTS. Conversely, in a meta-analysis of six studies
      (N=5202) conducted among office workers, CTS was positively associated with
      computer/typewriter use (pooled OR=1.34, 95% CI 1.08-1.65), mouse use (OR=1.93,
      95% CI 1.43-2.61), frequent computer use (OR=1.89, 95% CI 1.15-3.09), frequent
      mouse use (OR=1.84, 95% CI 1.18-2.87) and with years of computer work (OR=1.92,
      95% CI 1.17-3.17 for long vs. short). There was no evidence of publication bias
      for both types of studies. CONCLUSIONS: Studies that compared computer workers
      with the general population or several occupational groups did not control their
      estimates for occupational risk factors. Thus, office workers with no or little
      computer use are a more appropriate comparison group than the general population
      or several occupational groups. This meta-analysis suggests that excessive
      computer use, particularly mouse usage might be a minor occupational risk factor
      for CTS. Further prospective studies among office workers with objectively
      assessed keyboard and mouse use, and CTS symptoms or signs confirmed by a nerve
      conduction study are needed.

PMID- 25582981
TI  - Using mixed methods in health research: benefits and challenges.

PMID- 25582980
TI  - Concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized
      in Sri Lanka: implications for a potentially worldwide underestimated problem.
AB  - Two global (re-)emerging zoonoses, leptospirosis and hantavirus infections, are
      clinically indistinguishable. Thirty-one patients, hospitalized in Sri Lanka for
      acute severe leptospirosis, were after exclusion of other potentially involved
      pathogens, prospectively screened with IgM ELISA for both pathogens. Of these,
      nine (29.0%) were positive for leptospirosis only, one (3.2%) for hantavirus
      only, seven (22.5%) for both pathogens concomitantly, whereas 13 (41.9%) remained
      negative for both. Moreover, in a retrospective study of 23 former patients,
      serologically confirmed for past leptospirosis, six (26.0%) were also positive in
      two different IgG ELISA hantavirus formats. Surprisingly, European Puumala
      hantavirus (PUUV) results were constantly higher, although statistically not
      significantly different, than Asian Hantaan virus (HTNV), suggesting an
      unexplained cross-reaction, since PUUV is considered absent throughout Asia.
      Moreover, RT-PCR on all hantavirus IgM ELISA positives was negative. Concomitant
      leptospirosis-hantavirus infections are probably heavily underestimated
      worldwide, compromising epidemiological data, therapeutical decisions, and
      clinical outcome. 

PMID- 25582982
TI  - A case of invasive cytomegalovirus duodenitis in an immunosuppressed patient 15
      months after renal transplantation.
AB  - Cytomegalovirus (CMV) remains one of the most important infections in kidney
      transplantation. Only a handful of images have been reported in the literature
      thus far. We present classic pathologic and gross images of CMV duodenitis in an
      immunosuppressed patient more than one year post-renal transplantation. 

PMID- 25582984
TI  - Self-reported and verified compliance in a phase 3 clinical trial of a novel low
      dose contraceptive patch and pill.
AB  - OBJECTIVE: Pregnancy rates in US contraceptive clinical trials are increasing due
      to decreased treatment compliance. This study compared compliance with a new low
      dose levonorgestrel (LNG) and ethinyl estradiol (EE) contraceptive patch (CP,
      TwirlaTM) with that of a low-dose combination oral contraceptive (COC) in a
      demographically diverse population. STUDY DESIGN: This analysis was part of an
      open-label, parallel-group, multicenter phase 3 study that randomized healthy
      sexually active women (17-40years) to 13cycles of LNG/EE CP or 6cycles of COC,
      then 7cycles of LNG/EE CP. We defined self-reported compliance as cycles that,
      according to diaries, show 21days of patch wear without missed days or any patch
      worn >7days or 21days of pill-taking without missed pill days. We verified
      compliance by detectable plasma presence of LNG and EE at cycles 2, 6, and 13.
      RESULTS: Of the intention-to-treat population with diary information (N=1328,
      mean age 26.4years, 46% minorities, 33% obese), 10.0% of the CP (n=998) versus
      21.2% of the COC group (n=330) self-reported noncompliance after 6cycles
      (p<.001). Laboratory assessments verified 10-14% of participants in both groups
      as noncompliant. Self-reported perfect use did not vary between obese [body mass
      index (BMI) >=30kg/m(2)] versus nonobese (BMI <30kg/m(2)) participants in both
      groups or when stratified by age, education, or race/ethnicity in the CP group.
      CONCLUSIONS: Self-reported compliance was significantly greater in the CP than
      COC group and did not vary by obesity status. Discrepancies between self-reported
      and verified compliance question reliability of patient diaries. IMPLICATIONS
      STATEMENT: This paper, based on an analysis of a phase 3 trial, shows that
      compliance was significantly greater with a new weekly transdermal CP than with a
      once-daily COC in obese as well as nonobese participants. Discrepancies between
      self-reported compliance and laboratory-verified compliance raise questions
      regarding the reliability of patient diaries.

PMID- 25582985
TI  - Triglyceride micro-emulsion for detoxification of acute pharmacotoxicity.

PMID- 25582983
TI  - Hedgehog signaling stimulates the conversion of cholesterol to steroids.
AB  - Cholesterol modification of Hedgehog (Hh) ligands is fundamental for the activity
      of Hh signaling, and cholesterol biosynthesis is also required for intracellular
      Hh signaling transduction. Here, we investigated the roles and underlying
      mechanism of Hh signaling in metabolism of cholesterol. The main components of
      the Hh pathway are abundantly expressed in both human cytotrophoblasts and
      trophoblast-like cells. Activation of Hh signaling induces the conversion of
      cholesterol to progesterone (P4) and estradiol (E2) through up-regulating the
      expression of steroidogenic enzymes including P450 cholesterol side chain
      cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase type 1 (3beta
      HSD1), and aromatase. Moreover, inhibition of Hh signaling attenuates not only Hh
      induced expression of steroidogenic enzymes but also the conversion of
      cholesterol to P4 and E2. Whereas Gli3 is required for Hh-induced P450scc
      expression, Gli2 mediates the induction of 3beta-HSD1 and aromatase. Finally, in
      ovariectomized nude mice, systemic inhibition of Hh signaling by cyclopamine
      suppresses circulating P4 and E2 levels derived from a trophoblast-like
      choricarcinoma xenograft, and attenuates uterine response to P4 and E2. Together
      these results uncover a hitherto uncharacterized role of Hh signaling in
      metabolism of cholesterol. 

PMID- 25582987
TI  - Randomized Controlled Trial of an Improved Version of MobileMums, an Intervention
      for Increasing Physical Activity in Women with Young Children.
AB  - BACKGROUND: Women with young children (<5 years) are an important group for
      physical activity intervention. PURPOSE: The objective of the study was to
      evaluate the feasibility, acceptability, and efficacy of MobileMums-a physical
      activity intervention for women with young children. METHODS: Women were
      randomized to MobileMums (n = 133) or a control group (n = 130). MobileMums was
      delivered primarily via individually tailored text messages. Moderate to vigorous
      physical activity (MVPA) was measured by self-report and an accelerometer at
      baseline, end of the intervention (13 weeks), and 6 months later (9 months).
      Changes were analyzed using repeated-measures models. RESULTS: MobileMums was
      feasible to deliver and acceptable to women. Self-reported MVPA duration
      (minutes/week) and frequency (days/week) increased significantly post
      intervention (13-week intervention effect 48.5 min/week, 95 % credible interval
      (CI) [13.4, 82.9] and 1.6 days/week, 95 % CI [0.6, 2.6]). Intervention effects
      were not maintained 6 months later. No effects were observed in accelerometer
      derived MVPA. CONCLUSIONS: MobileMums increased women's self-reported MVPA
      immediately post-intervention. Future investigations need to target sustained
      physical activity improvements (ACTRN12611000481976).

PMID- 25582986
TI  - Transaortic valve implantation with the direct flow medical valve in an emergency
      situation of post-valvuloplasty severe aortic regurgitation.
AB  - New technology advances in transcatheter aortic valve implantation (TAVI) promise
      to improve outcomes and usability. The next generation Direct Flow Medical (DFM)
      valve is a non metallic, repositionable and retrievable bioprosthesis with a
      flexible system that provides an optimal circumferential seal. We report a case
      of TAVI complicated by massive aortic regurgitation after balloon aortic
      predilation. This case demonstrates that the design and delivery mode of the DFM
      valve is advantageous during this emergency situation. 

PMID- 25582988
TI  - Implicating Self-Control in the Mechanism by which Implementation Intentions
      Reduce Stress-Induced Unhealthy Eating: a Comment on O'Connor et al.

PMID- 25582990
TI  - Physiological Reactivity During Parent-Adolescent Discussions: Associations with
      Scaffolding Behaviors and Relationship Quality.
AB  - BACKGROUND: Parents and adolescents commonly discuss stressful experiences.
      However, little is known about the features of these conversations that may have
      implications for health. METHODS: One hundred five adolescents and their parents
      engaged in conversations about two challenging events, with parental
      contributions to the discussions coded for four scaffolding behaviors
      (reiterations, negations, move alongs, and new interpretations). Systolic blood
      pressure, diastolic blood pressure, and heart rate were measured in both
      participants at baseline and throughout the conversation. Parent-reported
      relationship quality was also assessed. RESULTS: For both parents and
      adolescents, negative scaffolding behaviors were associated with increased
      physiological reactivity, whereas positive scaffolding behaviors were associated
      with decreased reactivity. Furthermore, children in higher quality parent-child
      relationships showed greater reactivity to reiterations and lower reactivity to
      new interpretations, but those in lower quality relationships demonstrated the
      opposite patterns. CONCLUSIONS: Specific aspects of parent-child interactions
      appear to contribute to physiological responses to challenging events, which in
      turn may have implications for health.

PMID- 25582989
TI  - Information Avoidance Tendencies, Threat Management Resources, and Interest in
      Genetic Sequencing Feedback.
AB  - BACKGROUND: Information avoidance is a defensive strategy that undermines receipt
      of potentially beneficial but threatening health information and may especially
      occur when threat management resources are unavailable. PURPOSE: We examined
      whether individual differences in information avoidance predicted intentions to
      receive genetic sequencing results for preventable and unpreventable (i.e., more
      threatening) disease and, secondarily, whether threat management resources of
      self-affirmation or optimism mitigated any effects. METHODS: Participants (N =
      493) in an NIH study (ClinSeq(r)) piloting the use of genome sequencing reported
      intentions to receive (optional) sequencing results and completed individual
      difference measures of information avoidance, self-affirmation, and optimism.
      RESULTS: Information avoidance tendencies corresponded with lower intentions to
      learn results, particularly for unpreventable diseases. The association was
      weaker among individuals higher in self-affirmation or optimism, but only for
      results regarding preventable diseases. CONCLUSIONS: Information avoidance
      tendencies may influence decisions to receive threatening health information;
      threat management resources hold promise for mitigating this association.

PMID- 25582991
TI  - Should I fight or should I flight? How studying insect aggression can help
      integrated pest management.
AB  - Aggression plays a key role all across the animal kingdom, as it allows the
      acquisition and/or defence of limited resources (food, mates and territories) in
      a huge number of species. A large part of our knowledge on aggressive behaviour
      has been developed on insects of economic importance. How can this knowledge be
      exploited to enhance integrated pest management? Here, I highlight how knowledge
      on intraspecific aggression can help IPM both in terms of insect pests (with a
      focus on the enhancement of the sterile insect technique) and in terms of
      biological control agents (with a focus on mass-rearing optimisation). Then, I
      examine what implications for IPM can be outlined from knowledge about
      interspecific aggressive behaviour. Besides predator-pest aggressive interactions
      predicted by classic biological control, I focus on what IPM can learn from (i)
      interspecific aggression among pest species (with special reference to
      competitive displacement), (ii) defensive behaviour exhibited by prey against
      predaceous insects and (iii) conflicts among predaceous arthropods sharing the
      same trophic niche (with special reference to learning/sensitisation practices
      and artificial manipulation of chemically mediated interactions).

PMID- 25582993
TI  - [Osteoporosis in Rheumatoid Arthritis: role of the vitamin D/parathyroid hormone
      system].
AB  - Osteoporosis is a well-established extra-articular feature of Rheumatoid
      Arthritis (RA). Systemic inflammation seems to play a crucial role in causing an
      alteration of multiple homeostatic systems implied in bone health, such as the
      RANK/RANKL/Osteoprotegerin and Wnt/beta catenin pathways; several other causal
      factors have been called into question, including the chronic use of
      corticosteroids. Since vitamin D exerts important immune-regulatory roles, it has
      been claimed that derangement of the vitamin D/parathyroid hormone (PTH) system,
      a well-known determinant of bone health, may play a pathogenic role in
      autoimmunity; animal models and clinical data support this hypothesis.
      Furthermore, RA patients seem to be relatively refractory to vitamin D-induced
      PTH suppression. Therefore, the link between RA and osteoporosis might in part be
      due to alterations in the vitamin D/PTH system. A better understanding of the
      pathophysiology of this system may be crucial to prevent and cure osteoporosis in
      patients with inflammatory/autoimmune diseases. A major clinical correlate of the
      strict cooperation and interdependence between vitamin D and PTH is that
      correction of the vitamin D deficiency, at least in autoimmune diseases, should
      be targeted to PTH suppression. 

PMID- 25582994
TI  - Assessment of fatigue and dryness in primary Sjogren's syndrome: Brazilian
      version of "Profile of Fatigue and Discomfort - Sicca Symptoms Inventory (short
      form) (PROFAD-SSI-SF)".
AB  - OBJECTIVE: To perform a cross-cultural adaptation and validation of the Profile
      of Fatigue and Discomfort - Sicca Symptoms Inventory (short form) (PROFAD-SSI-SF)
      questionnaire assessing the subjective aspects of the symptoms of primary Sjogren
      syndrome (pSS), for the Brazilian Portuguese language. METHOD: Conceptual, of the
      item, semantic and operational equivalences were evaluated. The Brazilian version
      of PROFAD-SSI-SF was administered to 62 women with pSS according to the European
      American consensus 2002 to assess measurement equivalence. alpha-Cronbach was
      used for internal consistency; intraclass correlation coefficient (ICC) for
      intraobserver reproducibility; and Spearman correlation coefficient for validity
      by comparing with Patient Global Assessment (PaGA), EULAR Sjogren's Syndrome
      Patient Reported Index (ESSPRI), Functional Assessment of Chronic Illness Therapy
      Fatigue Subscale (FACIT-F) and EuroQOL (EQ-5D). RESULTS: The internal consistency
      of PROFAD, SSI and total score was 0.80; 0.78; and 0.87, respectively. The
      intraobserver reproducibility of total PROFAD was 0.89; of total SSI of 0.86; and
      total score of 0.89. In terms of validity, PROFAD correlated significantly with
      PaGA (r = 0.50), FACIT-F (r = 0.59), ESSPRI (r = 0.58) and all domains of EQ-5D,
      with the exception of Mobility. On the other hand, SSI correlated significantly
      with PaGA (r = 0.43), FACIT-F (r = 0.57), ESSPRI (r = 0.55) and most areas of EQ
      5D. The total score of PROFAD-SSI-SF had a non-statistically significant
      correlation only with Mobility domain and with 1-100 range of EQ-5D. CONCLUSION:
      The Portuguese version of PROFAD-SSI-SF proved to be an adaptable, reproducible
      and valid tool for the Brazilian Portuguese language.

PMID- 25582995
TI  - [Autoimmune diseases and autoantibodies in pediatric patients and their first
      degree relatives with immunoglobulin A deficiency].
AB  - INTRODUCTION: Clinical manifestations of Immunoglobulin A Deficiency (IgAD)
      include recurrent infections, atopy and autoimmune diseases. However, to our
      knowledge, the concomitant evaluations of autoimmune diseases and autoantibodies
      in a cohort of IgAD patients with current age > 10 years-old and their relatives
      have not been assessed. OBJECTIVES: To evaluate autoimmune diseases and the
      presence of autoantibodies in IgAD patients and their first-degree relatives.
      METHODS: A cross-sectional study was performed in 34 IgAD patients (current age >
      10 years-old) and their first-degree relatives. All of them were followed at a
      tertiary Brazilian primary immunodeficiency center: 27 children/adolescents and 7
      of their first-degree relatives with a late diagnosis of IgAD. Autoimmune
      diseases and autoantibodies (antinuclear antibodies, rheumatoid factor, and anti
      thyroglobulin, anti-thyroperoxidase and IgA class anti-endomysial antibodies)
      were also assessed. RESULTS: Autoimmune diseases (n=14) and/or autoantibodies
      (n=10, four of them with isolated autoantibodies) were observed in 18/34 (53%) of
      the patients and their relatives. The most common autoimmune diseases found were
      thyroiditis (18%), chronic arthritis (12%) and celiac disease (6%). The most
      frequent autoantibodies were antinuclear antibodies (2%), anti-thyroglobulin
      and/or anti-thyroperoxidase (24%). No significant differences were observed in
      the female gender, age at diagnosis and current age in IgAD patients with and
      without autoimmune diseases and/or presence of autoantibodies (p>0.05). The
      frequencies of primary immunodeficiency's in family, autoimmunity in family,
      atopy and recurrent infections were similar in both groups (p>0.05). CONCLUSION:
      Autoimmune diseases and autoantibodies were observed in IgAD patients during
      follow-up, reinforcing the necessity of a rigorous and continuous follow-up
      during adolescence and adulthood.

PMID- 25582996
TI  - Additive effects of zoledronic acid and propranolol on bone density and
      biochemical markers of bone turnover in osteopenic ovariectomized rats.
AB  - OBJECTIVES: The present study was designed to investigate further the efficacy
      and safety of zoledronic acid (ZOL) and propranolol (PRO) as monotherapy and
      combination therapy in a rat model of postmenopausal osteoporosis. METHODS:
      Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age.
      Twelve weeks post-surgery, rats were randomized into six groups: (1) sham +
      vehicle; (2) OVX + vehicle; (3) OVX + ZOL (100 MUg/kg, i.v. single dose); (4) OVX
      + ZOL (50 MUg/kg, i.v. single dose); (5) OVX + PRO (0.1 mg/kg, s.c. 5 days per
      week); (6) OVX + ZOL (50 MUg/kg, i.v. single dose) + PRO (0.1 mg/kg, s.c. 5 days
      per week) for 12 weeks. After treatment, femurs were tested for bone density,
      porosity and trabecular micro-architecture. Biochemical markers in serum and
      urine were also determined. RESULTS: Combined treatment with ZOL plus PRO
      corrected decrease in serum calcium and increase in serum alkaline phosphatase
      and tartarate resistant acid phosphatase level better than single-drug therapy
      using ZOL or PRO. Moreover, combined treatment with ZOL plus PRO corrected
      increase in urine calcium, phosphorous and creatinine level better than single
      drug therapy using ZOL or PRO. Combination therapy using ZOL plus PRO also
      preserved the trabecular micro-architecture and cortical bone porosity.
      CONCLUSION: These data suggest that combined treatment with ZOL plus PRO could be
      more effective approach for treating severe osteoporosis in humans.

PMID- 25582997
TI  - [Assessing the magnitude of osteoarthritis disadvantage on people's lives: the
      MOVES study].
AB  - INTRODUCTION: Osteoarthritis (OA) is one of the ten most disabling diseases in
      developed countries and one of the leading causes of pain and disability over the
      world. Early diagnosis increases the likelihood of preventing disease
      progression. OBJECTIVES: To estimate the prevalence of self-reported
      osteoarthritis and quality of life in Portuguese adults with 45 or more years
      old. METHODS: Observational, cross-sectional study, implemented in households by
      face-to-face interview. RESULTS: 1,039 subjects with mean age of 62 years and
      54.2% female were included. The prevalence of self-reported osteoarthritis was
      9.9%. Knees and hands were the most frequent site of disease. The prevalence of
      OA was higher in women and in participants without professional activity.
      Presence of OA was higher in participants with comorbidities. Most subjects have
      done some treatment at some point in time for this disease: 94.5% had drug
      therapy, 49.5% physiotherapy, and 19.8% physical activity. Pain was associated
      with height, with some disease locations specifically neck, lower spine and
      shoulders, SF12 scores of quality of life, and measurements of impact in daily
      living, severity of disease and disability. The impact of OA in daily living was
      greater in subjects that had been on sick leave or stopped working due to OA, had
      worse physical and mental health, and with more severe of disease. CONCLUSION:
      This study confirmed that osteoarthritis is a very relevant disease with a high
      potential impact on quality of life, function and work ability and because of its
      prevalence with a very high growing social impact.

PMID- 25582999
TI  - [High resolution peripheral quantitative computed tomography for the assessment
      of morphological and mechanical bone parameters].
AB  - High resolution peripheral quantitative computed tomography (HR-pQCT) is a new
      technology commercially available for less than 10 years that allows performing
      in vivo assessment of bone parameters. HR-pQCT assesses the trabecular thickness,
      trabecular separation, trabecular number and connectivity density and, in
      addition, cortical bone density and thickness and total bone volume and density
      in high-definition mode, which additionally allows obtaining digital constructs
      of bone microarchitecture. The application of mathematics to captured data, a
      method called finite element analysis (FEA), allows the estimation of the
      physical properties of the tissue, simulating supported loads in a non-invasive
      way. Thus, HR-pQCT simultaneously acquires data previously provided separately by
      dual energy x-ray absorptiometry (DXA), magnetic resonance imaging and
      histomorphometry, aggregating biomechanical estimates previously only possible in
      extracted tissues. This method has a satisfactory reproducibility, with
      coefficients of variation rarely exceeding 3%. Regarding accuracy, the method
      shows a fair to good agreement (r(2) = 0.37-0.97). The main clinical application
      of this method is in the quantification and monitoring of metabolic bone
      disorders, more fully evaluating bone strength and fracture risk. In rheumatoid
      arthritis patients, this allows gauging the number and size of erosions and
      cysts, in addition to joint space. In osteoarthritis, it is possible to
      characterize the bone marrow edema-like areas that show a correlation with
      cartilage breakdown. Given its high cost, HR-pQCT is still a research tool, but
      the high resolution and efficiency of this method reveal advantages over the
      methods currently used for bone assessment, with a potential to become an
      important tool in clinical practice. 

PMID- 25582998
TI  - [Is there a relationship between gouty arthritis and Mediterranean fever gene
      mutations?].
AB  - OBJECTIVE: Gouty arthritis and familial Mediterranean fever (FMF) share some
      clinical and pathological features such as being classified as auto inflammatory
      disease, association with inflammasome, short-lived intermittent arthritis, and
      good response to colchicine and anti-interleukin-1 treatments. As Mediterranean
      fever (MEFV) gene is the causative factor of FMF, we aimed to investigate the
      prevalence of MEFV gene mutations and their effect on disease manifestations in
      Turkish gouty arthritis patients. METHODS: Ninety-seven patients diagnosed with
      primary gouty arthritis (93M and 4 F, 54 [37-84] years) and 100 healthy controls
      (94M and 6 F, 57 [37-86] years) included in the study. All subjects were
      genotyped for the MEFV variations. Number of gout attacks, diuretic use, and
      history of nephrolithiasis and presence of tophus were also recorded. RESULTS:
      The carriage rate of MEFV mutations for patients and controls were 22.7% (n=22)
      and 24% (n=24) respectively. The comparison of the patient and control groups
      yielded no significant difference in terms of the MEFV mutations carriage rate
      (p=0.87). The allelic frequencies of the MEFV mutations in patients were 11.9%
      (n=23) and 14% (n=28) in controls (p=0.55). The presence of MEFV variants did not
      show any association with clinical features of gouty arthritis. The subgroup
      analysis of patients revealed that gouty arthritis patients with mutations had
      similar frequencies of tophus, history of nephrolithiasis and podogra compared to
      the ones without mutations (p>0.05). CONCLUSIONS: This study does not provide
      support for a major role of MEFV mutations in Turkish gouty arthritis patients.

PMID- 25583000
TI  - Feasibility of measurement of bone turnover markers in female patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate the feasibility of bone turnover markers (BTMs) for the
      assessment of bone metabolism in patients with systemic lupus erythematosus
      (SLE), according to the guidelines of the International Osteoporosis Foundation
      and the International Federation of Clinical Chemistry and Laboratory Medicine.
      METHODS: The study included 43 female SLE patients. Serum procollagen type I N
      propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin,
      PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were
      measured. RESULTS: PINP and CTX levels were elevated in SLE patients aged > 45 in
      comparison to those aged < 45, although with borderline significance (p = 0.05,
      respectively). Correlations were found between BTMs: the strongest being between
      PINP and osteocalcin (tau = 0.69, p < 0.05). PINP and osteocalcin were found to
      be associated with PTH (tau = 0.3, tau = 0.29, respectively, p < 0.05). Age
      correlated with PINP (tau = 0.23, p < 0.05). Elevated PINP was found more
      frequently than elevated osteocalcin or CTX, both in patients aged < 45 (p =
      0.001) and > 45 (p < 0.001). No significant difference in PINP, osteocalcin or
      CTX levels was found with respect to season, neither in the entire SLE group, nor
      in the under-45 or over-45 groups. Previous glucocorticoid treatment was not
      associated with difference in BTMs. CONCLUSIONS: Increased BTMs in SLE appear to
      predominantly reflect the pattern of bone remodeling related to age. Increased
      PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of
      bone disturbances with BTMs performed in accordance with international reference
      standards need to be included in the approach to SLE patients, in addition to
      bone mineral density assessment.

PMID- 25583001
TI  - [Anti-Mullerian hormone levels as a predictor of ovarian reserve in systemic
      lupus erythematosus patients: a review].
AB  - The anti-Mullerian hormone (AMH) is secreted from granulosa cells of growing
      ovarian follicles and appears to be the best endocrine marker capable of
      estimating ovarian reserve. Systemic lupus erythematosus (SLE) is an autoimmune
      disease that predominantly affects women of reproductive age and may negatively
      affect their fertility due to disease activity and the treatments used. Recently,
      several studies assessed AMH levels to understand the real impact of SLE and its
      treatment on fertility. 

PMID- 25583002
TI  - [Recommendations from the Brazilian Society of Rheumatology on the diagnosis and
      treatment of intestinal parasitic infections in patients with autoimmune
      rheumatic disorders].
AB  - Intestinal parasites - helminths and protozoa - are cosmopolitan diseases which
      are most prevalent in tropical regions. Patients with diagnoses of autoimmune
      rheumatic diseases have, due to the underlying disease or its treatment, an
      increased risk of occurrence of severe manifestations of intestinal parasites.
      Although the prevalence of these parasitic infections is very high in our
      environment, not always is the rheumatologist attentive to the need for
      investigation and treatment of helminthiasis and protozooses before the use of
      immunomodulatory, immunosuppressive therapies, and of biological drugs that are
      modifiers of the course of the disease. In this document, the Brazilian Society
      of Rheumatology establishes general recommendations on the diagnosis and
      treatment of intestinal parasitic infections in Brazil in patients with
      autoimmune rheumatic diseases, highlighting rheumatoid arthritis, systemic lupus
      erythematosus and spondyloarthritis. 

PMID- 25583003
TI  - Practical stereoselective synthesis of eribulin fragment toward building a hybrid
      macrocyclic toolbox.
AB  - A practical stereoselective synthesis to obtain the substituted furan ring as the
      substructure of eribulin is developed. An asymmetric syn-aldol and intramolecular
      oxy-Michael were two key steps in our approach. The functionalized furan
      derivatives were then utilized further to build the 14- and 12-membered
      macrocyclic diversity as trans- and cis-fused (C-29 and C-30) compounds. This is
      the first report of building a chemical toolbox with macrocyclic small molecules
      having trans- or cis-fused 14- or 12-membered rings containing the substructure
      of eribulin and its diastereomer. 

PMID- 25583004
TI  - A theoretical study of asymmetric electron transport through linearly aromatic
      molecules.
AB  - Electron transport through a series of polyacene molecules connected via a pi
      conjugated bridge (an anthracene molecule) was investigated theoretically by
      using the nonequilibrium Green's function formalism combined with density
      functional theory. The results have shown that the asymmetric current-voltage
      characteristics can be achieved by tuning the position of a side pi-bridge linked
      to the main conjugated backbone. The detailed analyses of the spatial
      distribution of molecular orbitals as well as the current density interpret how
      the location of pi-bridge strongly affects the intramolecular electronic
      coupling. The rectification in the molecular junction arises from the
      localization of the molecular orbitals near the Fermi level and the asymmetric
      shift of molecule orbital energy levels under positive and negative bias. The
      rectification ratio decreases with increasing the length of the pi-bridge which
      improves intramolecular electronic coupling between aromatic rings. Furthermore,
      the rectification properties of conjugated molecules are just slightly affected
      by the anchoring positions of thiol groups. These results demonstrated that the
      location and the length of pi-bridge, which induce the asymmetric intramolecular
      coupling, play key roles in the rectification of the linearly aromatic molecules.

PMID- 25583005
TI  - Cranial bone regeneration after cranioplasty using cryopreserved autogenous bone
      by a programmed freezer with a magnetic field in rats.
AB  - BACKGROUND: The purpose of this study was to develop a bone tissue bank using a
      programmed freezer with a magnetic field. Parietal bones were removed from rats
      and used for organ culture examination (non-cryopreserved, cryopreserved with a
      magnetic field (CAS) and cryopreserved without a magnetic field group). Next,
      other parietal bones were used for histological examination. The cryopreserved
      bones by a CAS freezer and dried bones were transplanted respectively. Control
      bones were replanted without cryopreservation. Animals were sacrificed at 4, 8,
      12 and 24 weeks after surgery. After organ culture, the isolated osteoblasts from
      parietal bones which were cryopreserved by a CAS freezer can survive and
      proliferate as much as non-cryopreserved group. Histological examinations showed
      new bone formation in control and CAS group. These results suggest that bone
      tissue cryopreservation by CAS freezer can be successfully used for bone grafting
      which may be a novel option for regeneration medicine.

PMID- 25583006
TI  - Effect of pre-storage on Lilium martagon L. seed longevity following
      cryopreservation.
AB  - BACKGROUND: The aim of the study was to compare different strategies for the
      cryopreservation of Lilium martagon L. seeds. MATERIALS AND METHODS: The starting
      material was seeds of the martagon lily (without or with a special pretreatment
      involving sucrose pre-culture dehydratation and desiccation) subjected to
      cryopreservation after preliminary storage under conventional conditions (-5
      degree C, 5 degree C, or 15 degree C). The effects of storage, pretreatment and
      cryopreservation on the seeds were assessed in terms of seed germination and
      phenotypic changes in the seedlings derived from those seeds. RESULTS: Subjecting
      the seeds to cold hardening or pretreatment did not affect significantly their
      germination capacity or the average germination time after cryopreservation.
      Combination of these strategies, however, significantly affected the capacity of
      the seeds to germinate. The highest germinability (100%) after cryopreservation
      was observed in the seeds stored at 15 degree C and subjected to sucrose pre
      culture dehydration and air flow desiccation (seed moisture content [MC] 13.1%),
      and in those seeds stored at the same temperature but subjected subsequently to 5
      h desiccation, not pretreated, with MC of 7.6 degree. Cryopreservation did not
      affect the germination capacity of the seeds but shortened the average
      germination time from 40.7 to 34.4 days. CONCLUSIONS: The obtained results
      demonstrate that a simple cryopreservation method without any special
      pretreatment of seeds can be used successfully for preserving L. martagon seeds.
      Neither the low temperature nor the sucrose concentration used affected the
      germination capacity or the average germination time of L. martagon seeds
      following cryopreservation.

PMID- 25583007
TI  - Can linoleic acid improve the quality of frozen thawed bull sperm?
AB  - BACKGROUND: Cryopreservation is known to have a detrimental effect on the
      motility, viability and membrane integrity of sperm cells. OBJECTIVE: The aim of
      this study was to investigate the effect of various amount of linoleic acid
      supplementation to the Tris extender, on bull sperm parameters, DNA integrity and
      oxidative stress after freeze-thawing. METHODS: Ejaculates were split into five
      aliquots and extended to a final concentration of 18x10(6) spermatozoa per ml
      with the base extender containing different doses of linoleic acid 0.125 ml,
      (L125); 0.250 ml (L250); 0.5 ml (L500), 1 ml (L1000) and no additive (control;
      L0). The extended samples were equilibrated slowly to 4 degree C for 4 h and then
      froze using a digital freezing machine. Frozen straws were thawed individually in
      water bath at 37 degree C for 30 s to analyse progressive motility and sperm
      motion characteristics as well as membrane integrity. Biochemical assays were
      performed in a spectrophotometer using commercial kits. DNA damage was evaluated
      by Comet Assay. RESULT: The addition of various linoleic acid did not improve the
      sperm subjective, CASA and progressive motilities, sperm motility characteristics
      and DNA integrity (P>0.05). L500 exhibited the greatest values for membrane
      integrity than that of the other groups (P<0.001). All supplementation groups led
      to lower percentages of tail abnormalities in comparison to the control
      (P<0.001). L500 and L1000 significantly decreased total abnormalities. In
      conclusion, our findings showed that L500 linoleic acid supplementation in semen
      extender was of great beneficial effect on frozen-thawed bull semen in terms of
      morphology and plasma membrane integrity.

PMID- 25583008
TI  - Sea urchin (Paracentrotus lividus) cryopreserved embryos survival and growth:
      effects of cryopreservation parameters and reproductive seasonality.
AB  - BACKGROUND: The cryopreservation of embryos can be a powerful biotechnological
      tool to supply all year-round biological material for sea urchin aquaculture
      production. This study investigates different methodological and biological
      factors that may affect the result of the cryopreservation process of sea urchin
      (Paracentrotus lividus) embryos. Our data indicate that neither embryo density
      nor the use of different cryopreservation containers presented effect on the
      cryopreservation outcome. Contrary to other marine invertebrates, for sea urchin
      embryo cryopreservation ultrapure water cannot be used as CPA solvent, yielding
      zero survival. After studying the reproductive parameters along the reproductive
      season, we found a positive correlation between both male and female Condition
      Index (C.I.), and between the oocyte weight and C.I. Both the histology study of
      female gonads and the C.I. variation, suggest that the sea urchin natural
      spawning period in the Ria de Vigo occurs between June and July. We found no
      correlation between any of the reproductive parameters monitored and the
      cryopreservation outcome.

PMID- 25583009
TI  - Influences of developmental stages, protective additives and concentrations of
      cryoprotective agents on the cryopreservation of Pacific oyster (Crassostrea
      gigas) larvae.
AB  - BACKGROUND: The selection of the optimal developmental stage, appropriate
      cryoprotectants (CPAs) and their concentrations is important for successful
      cryopreservation. OBJECTIVE: To investigate the effects of developmental stage
      and CPA concentrations on the cryopreservation of Pacific oyster (Crassostrea
      gigas) larvae. MATERIALS AND METHODS: Seven developmental stages, various CPAs
      and concentrations were investigated for optimizing cryopreservation of Pacific
      oyster larvae. The morphologies of pre-frozen and frozen-thawed larvae were
      evaluated using scanning electron microscopy and transmission electron
      microscopy. RESULTS: The survival rate of frozen-thawed larvae increased with
      developmental stage; late umbo veligers exhibited a survival as high as 98.6%.
      The addition of 0.2 M or 0.5 M sucrose improved the survival of larvae, and 2.0 M
      ethylene glycol (EG) positively influenced the survival of frozen-thawed larvae.
      Moreover, the frozen-thawed larvae possessed irregularly arranged cilia and
      displayed a rough surface shell and a round-lumped cilium head. CONCLUSION: The
      findings indicate that the most desirable cryopreservation of Pacific oyster
      larvae may occur at any developmental stage except for the early trochophore
      stage. Sucrose at 0.2 M or 0.5 M and EG at 2.0 M or 2.5 M are appropriate
      cryoprotectant additives.

PMID- 25583011
TI  - Cryopreservation of Populus trichocarpa and Salix dormant buds with recovery by
      grafting or direct rooting.
AB  - BACKGROUND: Methods are needed for the conservation of clonally maintained trees
      of Populus and Salix. In this work, Populus trichocarpa and Salix genetic
      resources were cryopreserved using dormant scions as the source explant.
      OBJECTIVE: We quantified the recovery of cryopreserved materials that originated
      from diverse field environments by using either direct sprouting or grafting.
      MATERIALS AND METHODS: Scions (either at their original moisture content of 48 to
      60% or dried to 30%) were slowly cooled to -35 degree C, transferred to the vapor
      phase of liquid nitrogen (LNV, -160 degree C), and warmed before determining
      survival. RESULTS: Dormant buds from P. trichocarpa clones from Westport and
      Boardman, OR had regrowth levels between 42 and 100%. Direct rooting of
      cryopreserved P. trichocarpa was also possible. Ten of 11 cryopreserved Salix
      accessions, representing 10 different species, exhibited at least 40% bud growth
      and rooting after 6 weeks when a bottom-heated rooting system was implemented.
      CONCLUSION: We demonstrate that dormant buds of P. trichocarpa and Salix
      accessions can be cryopreserved and successfully regenerated without the use of
      tissue culture.

PMID- 25583010
TI  - MALD-TOF study of peptides from cryopreserved tissue fragments.
AB  - BACKGROUND: Previously it was shown that the extracts of cryopreserved organ
      fragments, containing tissue specific peptides, stimulates the reparative
      regeneration. In order to define the mechanism of action, it is necessary to
      determine the peptidic composition of extracts. OBJECTIVE: To examine molecular
      mass distribution of peptides in the extracts of cryopreserved fragments of pigs'
      heart and spleen as well as piglets' heart and skin. MATERIALS AND METHODS: The
      extracts were obtained from cryopreserved fragments of porcine organs. MALDI-ToF
      method was used to study the peptidic composition of the extracts. RESULTS: The
      most intense mass spectra peaks, which may correspond to single peptidic
      molecules, were compared with Protein Knowledgebase (UniProtKB) data. A number of
      recorded peptides in the extracts expresses high biological activity.

PMID- 25583012
TI  - Comparative analysis of cryoprotective agents influence on thermodynamic and
      kinetic parameters of equine and human hemoglobin molecules.
AB  - BACKGROUND: Critical to the understanding the mechanism of destruction and
      protection during cryopreservation of biological objects is the knowledge of the
      conformational transitions of biopolymers experiencing low temperatures in the
      presence of cryoprotective agents. This information may be derived from the
      kinetic and thermodynamic parameters of macromolecular thermal denaturation
      kinetics under different environmental conditions. OBJECTIVE: The study deals
      with the influence of cryoprotective agents (glycerol, 1.2-propanediol (1.2-PD),
      and dimethyl sulfoxide (DMSO)) on thermodynamic and kinetic parameters of equine
      and human hemoglobin. METHODS: Thermograms were recorded with differential
      scanning adiabatic microcalorimeter (DASM-4, Biopribor, Russia). RESULTS:
      Temperatures and enthalpy changes in the denaturation of hemoglobins (DeltaHcal)
      in the presence of cryoprotective agents from 0-40% (w/w) were determined. Within
      the whole concentration range glycerol slightly alters the hemoglobin
      denaturation temperature while DMSO and 1.2-PD lead to a significant decrease.
      The addition of cryoprotectants to hemoglobin solutions induces a complex
      behavior of DeltaHcal concentration dependences of denaturation caused by intra-
      and intermolecular processes such as hydration of the porphyrin cycle, heme
      cleavage from heme-containing proteins, disorder in hydrophobic contacts with
      globin etc. These factors may decrease thermal stability by loosening hemoglobin
      molecules and spatial disruption of fragments of the protein. Activation energy
      of irreversible unfolding of equine hemoglobin at heating was estimated using the
      approach of Sanchez-Ruiz et al. DMSO and 1.2-PD decreased activation energy
      values. CONCLUSIONS: The data indicate the reduction of protein thermal stability
      by DMSO and 1.2-PD. Glycerol slightly increases hemoglobin thermal stability
      within the studied range of concentrations.

PMID- 25583013
TI  - Approaches for the cryopreservation of Plantago algarbiensis, a rare endemic
      species of the Algarve.
AB  - BACKGROUND: Plantago algarbiensis is an endangered endemic species from the
      Algarve, Portugal. OBJECTIVE: The main goal of this study was to investigate the
      viability of cryopreservation procedures in the conservation of seeds and nodal
      explants from this species. MATERIALS AND METHODS: Seeds were directly immersed
      in liquid nitrogen (LN) for 30 days. Two methods were tested for the
      cryopreservation of nodal explants, namely droplet-vitrification and
      encapsulation-dehydration. For both methods, nodal segments were precultured on
      Murashige and Skoog (MS) medium and recovered on MS supplemented with 0.2 mg l(
      1) 6-benzyladenine (BA), after freezing. RESULTS: After 30 days in LN, the
      germination capacity of seeds was not affected. The regrowth percentages of
      cryopreserved nodal segments were approximately 60%. With the droplet
      vitrification method, a regrowth percentage of 60.0+/-15.2% was obtained after
      120 min exposure to PVS2 (plant vitrification solution 2) and with encapsulation
      dehydration method the highest percentage, 63.3+/-9.6%, was achieved after 3 h
      desiccation. CONCLUSION: Seed cryopreservation and cryopreservation of nodal
      segments by droplet-vitrification and encapsulation-dehydration are therefore
      effective approaches for the conservation of P. algarbiensis.

PMID- 25583015
TI  - Influence of the toxicity of cryoprotective agents on the involvement of insulin
      like growth factor-I receptor in surf clam (Spisula sachalinensis) larvae.
AB  - BACKGROUND: The signaling of insulin-like growth factor-I (IGF-I) is involved in
      the development, growth, reproduction and aging of vertebrates. However, few
      studies have investigated the involvement of IGF-I during states of extreme
      shock, such as those induced by potently toxic cryoprotective agents (CPAs) or
      low temperature conditions, in bivalves. OBJECTIVE: We investigated the toxicity
      of CPAs and the potential relationship between larval viability and the IGF-I
      receptor (IGF-IR) after treatment with CPAs or freezing in surf clam (Spisula
      sachalinensis) larvae. MATERIALS AND METHODS: The umbo larvae and different
      concentrations of CPAs (dimethyl sulfoxide, DMSO; ethylene glycol, EG) were used
      to investigate the toxicity of CPAs and the vitrification of surf clam larvae.
      The relationship between larval viability and the IGF-I receptor (IGF-IR) after
      treatment with CPAs or freezing was investigated using immunoblot analysis.
      RESULTS: An increase in concentration greater than 4M DMSO was fatal in larvae;
      however, 5M EG combined with a mixture of CPAs had no harmful effects. Moreover,
      live larvae immersed in a 5M EG solution remained intact and maintained their
      normal shape and organs. However, even though the larvae survived the CPA
      toxicity test, none of the vitrified larvae survived. After immersion into CPAs
      and vitrification, 97-kDa IGF-IR beta-subunits could be detected in all larvae;
      but tyrosine phosphorylation of the intracellular beta-subunits was detected only
      in the control and live groups. CONCLUSION: IGF-IR was activated in the umbo
      larvae but not in dead surf clam larvae treated with CPA and frozen. Activation
      of IGF-IR has relevance to the umbo larval stage in live surf clams treated with
      CPAs.

PMID- 25583014
TI  - Effect of caffeine treatment before vitrification on MPF and MAPK activity and
      spontaneous parthenogenetic activation of in vitro matured ovine oocytes.
AB  - BACKGROUND: Molecules that stabilize protein kinases may be useful in overcoming
      the deleterious effects of cryopreservation. OBJECTIVE: To evaluate the effect of
      caffeine treatment before vitrification of in vitro matured ovine oocytes on the
      activity of MPF and MAPK as well as the spontaneous parthenogenetic activation
      after 24 h culture. MATERIALS AND METHODS: Oocytes obtained from slaughterhouse
      sheep ovaries were in vitro matured for 21 h, incubated for 3 h with or without
      caffeine and then vitrified. After warming, oocytes were processed for the
      analysis of chromatin configuration and the evaluation of spontaneous
      parthenogenetic activation (24 h in vitro culture). Fresh in vitro matured
      oocytes were used as control. RESULTS: Caffeine treatment before vitrification
      maintained the MPF activity at a level similar to that of fresh oocytes, and
      reduced the spontaneous parthenogenetic activation in comparison with oocytes
      that were not-treated with caffeine. CONCLUSION: Caffeine treatment prolongs the
      meiotic arrest of vitrified MII oocytes, likely via its action of stabilizing the
      MPF level.

PMID- 25583016
TI  - Confocal microscopic analysis of the microfilament configurations from human
      vitrification-thawed oocytes matured in vitro.
AB  - BACKGROUND: The alteration in microfilaments of human oocytes by vitrification
      has not been understood well. OBJECTIVE: To evaluate the effect of vitrification
      on the microfilaments of human in vitro matured oocytes and the time needed for
      the repair. MATERIALS AND METHODS: Human in vitro matured oocytes were divided
      into the control group (Group 1) and the vitrified group. The vitrified oocytes
      were further divided into four sub-groups that were cultured after thawing for 1
      h, 2 h, 3 h and 4 h, respectively (Groups 2, 3, 4 and 5). RESULTS: The survival
      rate of oocytes was 87.4% after vitrification and thawing. The percentage of
      oocytes with a normal configuration of microfilaments in Group 2 and Group 3 was
      significantly lower than that of the fresh control group (Group 1), whereas the
      percentage of oocytes with normal microfilament configuration in Group 4 and
      Group 5 was comparable to the control group. CONCLUSION: Vitrification alters
      microfilament structure of oocytes, which takes at least 3h after thawing for the
      repair and recovery.

PMID- 25583017
TI  - Prognostic indicators in well-differentiated thyroid carcinoma when controlling
      for stage and treatment.
AB  - OBJECTIVES/HYPOTHESIS: The incidence of thyroid carcinoma is rising. Few studies
      have examined patient characteristics that influence survival when adjusting for
      treatment and tumor stage/extent. STUDY DESIGN: Retrospective analysis was
      performed using the Surveillance Epidemiology and End Results registry data among
      patients diagnosed with well-differentiated thyroid (WDT) carcinoma during 1988
      2009. METHODS: Kaplan-Meir survival curves were used to estimate 5- and 10-year
      cause-specific and overall survival differences by sociodemographics, clinical
      characteristics, and treatment. Multivariate Cox proportional hazard models were
      used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:
      A total of 83,985 patients were identified with WDT carcinoma. Blacks had higher
      hazard of death at 5 years (HR, 1.67; 95% CI, 1.42-1.96) and 10 years (HR, 1.57;
      95% CI, 1.37-1.80) when compared to Caucasians, but there were no significant
      differences in cause-specific deaths. Hispanics had higher overall and cause
      specific 5-year and 10-year hazard of death (5-year cause-specific: HR, 1.56; 95%
      CI, 1.23-1.99). Age was the most significant predictor of cause-specific and
      overall survival, with risk increasing in a nonlinear fashion. After age 45
      years, the HR for 5- and 10-year cause-specific survival rose drastically,
      reaching an HR of 153 for individuals aged 85 years and older (HR, 153.45; 95%
      CI, 97.84-240.67). CONCLUSIONS: Age was the strongest factor associated with WDT
      cancer in our study. African Americans had worse overall survival, although only
      Hispanics had a significantly worse cause-specific survival. These factors should
      be taken into account in counseling patients and treatment planning.

PMID- 25583018
TI  - Enzyme-assisted extraction of anticoagulant polysaccharide from Liparis
      tessellatus eggs.
AB  - This study aimed to recover a heparin-like anticoagulant polysaccharide from
      Liparis tessellatus eggs (PLE) by using enzyme-assisted extraction technique.
      Extraction experiments were carried out using three different enzymes
      (Alcalase(r)2.4 L, Flavourzyme(r)500 MG, and Protamex(r)) under different
      conditions of temperature (45, 50, and 55 degrees C), pH (6.5, 7.0, and 7.5),
      incubation time (24, 36, and 48 h), and enzyme to substrate ratio (E/S=0.5, 1.0,
      and 1.5%, w/w), which were combined according to a D-optimal design. Statistical
      analysis of extraction results allowed identifying the variables with greater
      influence on the extraction yield, and selecting the conditions that maximize the
      PLE extraction. The best extraction results were achieved when using the
      Protamex(r) enzyme in an E/S ratio of 1.34% (w/w), pH 6.60, 47.40 degrees C,
      during 26.50 h. Under these conditions, a polysaccharide yield of 2.10% (w/w) was
      obtained. Clotting time measurements, activated partial thromboplastin time, and
      prothrombin time for evaluation of the anticoagulant properties of PLE were
      determined and showed increasing activities in correlation with the
      concentrations used. In the final step, the heparin-like nature of PLE was
      confirmed by digestion with heparinases I, II, and III, which showed DeltaDiHS
      0S, DeltaDiHS-6S, DeltaDiHS-diS1, and DeltaDiHS-diS2 at compositions of 0.04,
      0.03, 0.35, and 0.24 mol/g, respectively.

PMID- 25583019
TI  - Characterization of two water-soluble lignin metabolites with antiproliferative
      activities from Inonotus obliquus.
AB  - The chaga mushroom, Inonotus obliquus has long been recognized as a remedy for
      cancer, gastritis, ulcers, and tuberculosis of the bones since the 16th century.
      Herein we reported the identification of two homogenous biological
      macromolecules, designated as IOW-S-1 and IOW-S-2 with anti-tumor activities from
      the hot-water extract of I. obliquus. Their molecular weights were determined to
      be 37.9 and 24.5kDa by high performance gel permeation chromatography (HPGPC)
      respectively. Chemical and spectral analysis indicated that both IOW-S-1 and IOW
      S-2 were predominant in lignin, along with ~20% carbohydrates. Examination of
      cytotoxicity showed that these two lignin-carbohydrate complexes induced cell
      death in a concentration dependent manner, while this apoptosis induction was
      largely cell-cycle independent. Further investigation demonstrated that IOW-S-1
      or IOW-S-2 inhibited the activation of the nuclear transcription factor in cancer
      cells. These findings implied that soluble lignin derivatives were one of
      bioactive components in I. obliquus, and further provided insights into the
      understanding of molecular basis for diverse medicinal and nutritional values of
      this mushroom. 

PMID- 25583020
TI  - Density functional theory studies of Pb (II) interaction with chitosan and its
      derivatives.
AB  - Density functional theory (DFT) studies of Pb (II) ions interaction with
      biopolymer chitosan and its derivatives are presented. Schiff bases and N
      alkylated/arylated derivatives of chitosan were characterized as adsorbents of
      lead ions and are studied at monomer level. Natural bond orbital (NBO) analysis
      was carried out for chitosan and derivatives to understand the donor-acceptor
      interactions. Molecular electrostatic potential (MEP) maps of the adsorbents were
      plotted with color code. Global reactivity parameters of adsorbents were
      calculated on the basis of frontier molecular orbital (FMO) energies. Structure
      of complexes formed between chitosan and derivatives with Pb (II) ion were
      examined at B3LYP/LanL2DZ level of DFT. The stability of the complexes are
      discussed based on the values of Eads. We observed that the N-reduced pyridine
      carboxaldehyde derivative of chitosan (RPC) forms more stable complex with Pb
      (II) ions than with other derivatves. 

PMID- 25583021
TI  - Anti-HSV1 activity of brown algal polysaccharides and possible relevance to the
      treatment of Alzheimer's disease.
AB  - Herpes simplex virus type 1 (HSV1) induces the formation of the characteristic
      abnormal molecules of Alzheimer's disease (AD) brains, beta-amyloid, and
      abnormally phosphorylated, AD-like tau (P-tau). Formation of these molecules is
      inhibited by treatment with the antiviral agent acyclovir (ACV), which prevents
      viral DNA replication. A totally different mechanism of antiviral action against
      herpes simplex viruses is shown by sulfated fucans. The antiviral activity of
      sulfated fucans from five brown algae (Scytothamnus australis, Marginariella
      boryana, Papenfussiella lutea, Splachnidium rugosum and Undaria pinnatifida) was
      investigated in relation to the HSV1-induced formation of beta-amyloid, and AD
      like tau. Antiviral activity was also related to specific structural features of
      these polysaccharides. Four sulfated fucan extracts each prevented the
      accumulation of HSV1-induced beta-amyloid and AD-like tau in HSV1-infected Vero
      cells. The structures of these extracts had some similarities but also key
      differences, indicating that a number of structural features can cause antiviral
      activity. The most active sulfated fucan combined with acyclovir was particularly
      effective, so may be particularly suitable for further experimental testing in
      order to develop treatment protocols for AD patients, with the aim of slowing or
      stopping disease progression. 

PMID- 25583023
TI  - Water soluble polysaccharides from Spirulina platensis: extraction and in vitro
      anti-cancer activity.
AB  - Polysaccharides from Spirulina platensis algae (SP) were extracted by ultrasound
      assisted extraction procedure. The optimal conditions for ultrasonic extraction
      of SP were determined by response surface methodology. The four parameters were,
      extraction time (X1), extraction temperature (X2), ultrasonic power (X3) and the
      ratio of water to raw material (X4), respectively. The experimental data obtained
      were fitted to a second-order polynomial equation. The optimum conditions were
      extraction time of 25 min, extraction temperature 85 degrees C, ultrasonic power
      90 W and ratio of water to raw material 20 mL/g. Under these optimal conditions,
      the experimental yield was 13.583+/-0.51%, well matched with the predicted models
      with the coefficients of determination (R2) of 0.9971. Then, we demonstrated that
      SP polysaccharides had strong scavenging activities in vitro on DPPH and hydroxyl
      radicals. Overall, SP may have potential applications in the medical and food
      industries.

PMID- 25583022
TI  - Alginate-calcium microsphere loaded with thrombin: a new composite biomaterial
      for hemostatic embolization.
AB  - To date, transcatheter arterial embolization (TAE) has become a standard
      treatment to control intracavitary bleeding as an alternative to surgery. Due to
      excellent biocompatibility and no residual in vivo, biodegradable materials are
      preferred in TAE. However, gelfoam is the only commercially available
      biodegradable embolic material used to treat blunt trauma of solid abdominal
      viscera until now, and controversial on its stability and reliability never
      stopped in the past five decades. In this study, a new biodegradable
      macromolecule material (thrombin-loaded alginate-calcium microspheres, TACMs) was
      prepared using electrostatic droplet techniques and a special method was
      developed for hemostatic embolization. Thrombin was successfully loaded into
      microspheres with high encapsulation efficiency and drug loading capacity. A
      burst release of TACMs was observed at early stage and sustained release later
      on, with the activity of thrombin preserved well. The strength of TACMs mixed
      thrombus, which was used as embolic agent, increased in a dose-dependent manner
      after TACMs were added. In addition, the TACMs were verified to be of no
      cytotoxicity and systemic toxicity, and biodegradable in vivo. Finally, the
      results of preliminary applications revealed that the TACMs could serve as an
      effective and promising embolic material for blunt trauma and hemorrhage of solid
      abdominal viscera. 

PMID- 25583024
TI  - Anti-metastatic effects of antrodan, the Antrodia cinnamomea mycelia
      glycoprotein, in lung carcinoma cells.
AB  - This study investigated the anti-metastatic effects of antrodan, the glycoprotein
      from Antrodia cinnamomea (AC) mycelia, through direct actions and indirect
      immunomodulatory effects in Lewis lung carcinoma (LLC). Antrodan was isolated
      from AC mycelia by alkali extraction, acid precipitation, and purification using
      sepharose CL-6B column chromatography. In the direct anti-metastatic action,
      antrodan (30-70 MUg/mL) was found to significantly inhibit invasion and migration
      of LLC cells, and these effects involved up-regulation of tissue inhibitor of
      matrix metalloproteinase (TIMP)-1, TIMP-2, and nm23-H1 protein expression leading
      to decreased activities and protein expression of MMP-2 and MMP-9. For testing
      the indirect immunomodulatory effect, antrodan was incubated for 3d with
      mononuclear cells (MNCs) isolated from human peripheral blood to obtain the
      condition medium (CM). Antrodan significantly increased interleukin (IL)-12 and
      IL-1beta levels, but decreased TNF-alpha, IL-6 and IL-8 levels in the MMC-CM,
      which also significantly inhibited invasion, migration, and the activities and
      protein expression of MMP-2 and MMP-9, but significantly increased protein
      expression of TIMP-1, TIMP-2, and nm23-H1 in LLC cells. The indirect
      immunomodulatory effect of antrodan was stronger than the direct anti-metastatic
      effect at the same concentrations (50 and 60 MUg/mL). Overall, the results
      suggest the anti-metastatic potential of antrodan in LLC cells.

PMID- 25583026
TI  - Recent approaches for the direct use of elemental sulfur in the synthesis and
      processing of advanced materials.
AB  - Elemental sulfur is an abundant and inexpensive material obtained as a by-product
      of natural-gas and petroleum refining operations. Recently, the need for the
      development of new energy-storage systems brought into light the potential of
      sulfur as a high-capacity cathode material in secondary batteries. Sulfur
      containing materials were also shown to have useful IR optical properties. These
      developments coupled with growing environmental concerns related to the global
      production of excess elemental sulfur have led to a keen interest in its
      utilization as a feedstock in materials applications. This Minireview focuses on
      the recent developments on physical and chemical methods for directly processing
      elemental sulfur to produce functional composites and polymers. 

PMID- 25583025
TI  - Phosphoinositide 3-kinase p110delta promotes lumen formation through the
      enhancement of apico-basal polarity and basal membrane organization.
AB  - Signalling triggered by adhesion to the extracellular matrix plays a key role in
      the spatial orientation of epithelial polarity and formation of lumens in
      glandular tissues. Phosphoinositide 3-kinase signalling in particular is known to
      influence the polarization process during epithelial cell morphogenesis. Here,
      using Madin-Darby canine kidney epithelial cells grown in 3D culture, we show
      that the p110delta isoform of phosphoinositide 3-kinase co-localizes with focal
      adhesion proteins at the basal surface of polarized cells. Pharmacological, siRNA
      or kinase-dead-mediated inhibition of p110delta impair the early stages of lumen
      formation, resulting in inverted polarized cysts, with no laminin or type IV
      collagen assembly at cell/extracellular matrix contacts. p110delta also regulates
      the organization of focal adhesions and membrane localization of dystroglycan.
      Thus, we uncover a previously unrecognized role for p110delta in epithelial cells
      in the orientation of the apico-basal axis and lumen formation. 

PMID- 25583027
TI  - Response to "importance of C-3 epimer of 25-hydroxyvitamin D in dried blood spots
      of neonatal population".

PMID- 25583028
TI  - MoTup1 is required for growth, conidiogenesis and pathogenicity of Magnaporthe
      oryzae.
AB  - The general transcriptional repressor Tup1 proteins play important regulatory
      roles in the growth and development of fungi. In this report, we characterized
      MoTup1, a protein homologous to Tup1 of Saccharomyces cerevisiae, from M. oryzae.
      Disruption of MoTUP1 resulted in severe mycelial growth reduction and a defect in
      conidiogenesis. We found that MoTup1 is required for the maintenance of cell wall
      integrity by regulating the expression of the genes involved in cell wall
      biosynthesis. Pathogenicity assays indicated that the DeltaMotup1 mutants lost
      the ability to invade both rice and barley hosts. Moreover, observation of rice
      epidermis penetration showed that the hyphal tips of the mutants could still form
      appressorium-like structures, but were unable to invade host cells. Taken
      together, our results demonstrate that M. oryzae MoTup1 is an important
      regulatory factor in fungal growth, development and pathogenesis on hosts.

PMID- 25583029
TI  - Designing and evaluating an interactive multimedia Web-based simulation for
      developing nurses' competencies in acute nursing care: randomized controlled
      trial.
AB  - BACKGROUND: Web-based learning is becoming an increasingly important
      instructional tool in nursing education. Multimedia advancements offer the
      potential for creating authentic nursing activities for developing nursing
      competency in clinical practice. OBJECTIVE: This study aims to describe the
      design, development, and evaluation of an interactive multimedia Web-based
      simulation for developing nurses' competencies in acute nursing care. METHODS:
      Authentic nursing activities were developed in a Web-based simulation using a
      variety of instructional strategies including animation video, multimedia
      instructional material, virtual patients, and online quizzes. A randomized
      controlled study was conducted on 67 registered nurses who were recruited from
      the general ward units of an acute care tertiary hospital. Following a baseline
      evaluation of all participants' clinical performance in a simulated clinical
      setting, the experimental group received 3 hours of Web-based simulation and
      completed a survey to evaluate their perceptions of the program. All participants
      were re-tested for their clinical performances using a validated tool. RESULTS:
      The clinical performance posttest scores of the experimental group improved
      significantly (P<.001) from the pretest scores after the Web-based simulation. In
      addition, compared to the control group, the experimental group had significantly
      higher clinical performance posttest scores (P<.001) after controlling the
      pretest scores. The participants from the experimental group were satisfied with
      their learning experience and gave positive ratings for the quality of the Web
      based simulation. Themes emerging from the comments about the most valuable
      aspects of the Web-based simulation include relevance to practice, instructional
      strategies, and fostering problem solving. CONCLUSIONS: Engaging in authentic
      nursing activities using interactive multimedia Web-based simulation can enhance
      nurses' competencies in acute care. Web-based simulations provide a promising
      educational tool in institutions where large groups of nurses need to be trained
      in acute nursing care and accessibility to repetitive training is essential for
      achieving long-term retention of clinical competency.

PMID- 25583032
TI  - Tuning phonon properties in thermoelectric materials.
AB  - This review article presents a discussion of theoretical progress made over the
      past several decades towards our understanding of thermoelectric properties of
      materials. Particular emphasis is placed upon describing recent progress in
      'tuning' phonon properties of nanocomposite materials for gaining enhancement of
      the thermoelectric figure of merit. 

PMID- 25583031
TI  - Landscape cultivation alters delta30Si signature in terrestrial ecosystems.
AB  - Despite increasing recognition of the relevance of biological cycling for Si
      cycling in ecosystems and for Si export from soils to fluvial systems, effects of
      human cultivation on the Si cycle are still relatively understudied. Here we
      examined stable Si isotope (delta(30)Si) signatures in soil water samples across
      a temperate land use gradient. We show that - independent of geological and
      climatological variation - there is a depletion in light isotopes in soil water
      of intensive croplands and managed grasslands relative to native forests.
      Furthermore, our data suggest a divergence in delta(30)Si signatures along the
      land use change gradient, highlighting the imprint of vegetation cover, human
      cultivation and intensity of disturbance on delta(30)Si patterns, on top of more
      conventionally acknowledged drivers (i.e. mineralogy and climate). 

PMID- 25583030
TI  - Purification and identification of high molecular weight products formed during
      storage of neutral formulation of human insulin.
AB  - PURPOSE: To identify High Molecular Weight Products (HMWP) formed in human
      insulin formulation during storage. METHODS: Commercial formulation of human
      insulin was stored at 37 degrees C for 1 year and HMWP was isolated using
      preparative size exclusion chromatography (SEC) and reverse phase (RP)
      chromatography. The primary structure of the isolated species was analysed using
      liquid chromatography mass spectrometry (LC-MS) and tandem mass spectrometry
      (MS/MS). To test the hypothesis that amino groups of insulin are involved in HMWP
      formation, the HMWP content of various formulations spiked with amine compounds
      or formulations of insulin with modified amino groups was measured. RESULTS: More
      than 20 species of HMWP were observed and 16 species were identified using LC-MS.
      All identified species were covalent dimers of human insulin linked via A21Asn
      and B29Lys, formed via the formation of an anhydride intermediate at A21Asn. Two
      types of HMWP were identified, with the covalent link in the open or closed
      (succinimidyl) form. Some species also contained single deamidation at B3 or the
      desPhe(B1)-N-oxalyl-Val(B2) modification. Reduced rate of HMWP formation was
      observed after addition of L-lysine, L-arginine or piperazine or when insulin
      analogues with methylated N-terminals and side chain amines and A21Gly mutation
      were used. Formulations of human insulin without zinc and m-cresol were found to
      contain a different pool of HMWP. CONCLUSIONS: HMWP formed in formulation of
      human insulin at pH 7.4 with zinc and m-cresol consists primarily of covalent
      dimers linked via A21Asn and B29Lys. Insulin formulation properties determine the
      amount and identity of formed HMWP.

PMID- 25583033
TI  - Editorial: facts, figures and the future.

PMID- 25583034
TI  - How the Breast Journal pioneered the concept of advancing multi-disciplinary
      breast health education at a global level.

PMID- 25583035
TI  - Extreme oncoplasty: breast conservation for patients who need mastectomy.
AB  - Extreme oncoplasty is a breast conserving operation, using oncoplastic
      techniques, in a patient who, in most physicians' opinions, requires a
      mastectomy. These are generally large, greater than 5 cm multifocal or
      multicentric tumors. Many will have positive lymph nodes. Most will require
      radiation therapy, even if treated with mastectomy. Sixty-six consecutive
      patients with multifocal, multicentric, or locally advanced tumors that spanned
      more than 50 mm were studied (extreme cases). All patients underwent excision and
      oncoplastic reconstruction using a standard or split wise pattern reduction and
      immediate contralateral surgery for symmetry. All received postexcisional
      standard whole breast radiation therapy with a boost to the tumor bed. The
      extreme cases were compared with 245 consecutive patients with unifocal or
      multifocal tumors that spanned 50 mm or less (standard cases). All extreme
      patients were advised to have a mastectomy; all sought a breast conserving second
      opinion. Diagnostic evaluation included digital mammography, ultrasound, MRI, and
      PET-CT (if invasive). Standard cases did extremely well. No ink on tumor was
      achieved 96% of the time among 245 patients. The median tumor size was 21 mm
      (mean 23 mm). Margins equal or greater than 1 mm were achieved in 88.6% of
      patients. Seventeen (6.9%) standard patients underwent re-excision to achieve
      wider margins and only one patient (0.4%) was converted to mastectomy. With 24
      months of median follow-up, three patients (1.2%) experienced local recurrence.
      For extreme cases, no ink on tumor was achieved 83.3% of the time, which is
      comparable to published positive margin rates after standard lumpectomy. The
      median tumor size was 62 mm (mean 77 mm). Margins equal or greater than 1 mm were
      achieved in 54.5% of patients. Six (9.1%) extreme patients underwent re-excision
      to achieve wider margins and four patients (6.1%) were converted to mastectomy.
      With a follow-up of 24 months, one patient (1.5%) experienced a local recurrence.
      Extreme oncoplasty is a promising new concept. It allows successful breast
      conservation in selected patients with greater than 5 cm multifocal/multicentric
      tumors. It may be useful in patients with locally advanced tumors following neo
      adjuvant chemotherapy. From a quality of life point of view, it is a better
      option than the combination of mastectomy, reconstruction, and radiation therapy.
      Long-term data on recurrence and survival are not available, using this approach.
      Based on historical data, it is expected the local recurrence will be somewhat
      higher but that there will be little or no impact on survival. 

PMID- 25583036
TI  - Biliary tract reconstruction with or without T-tube in orthotopic liver
      transplantation: a systematic review and meta-analysis.
AB  - INTRODUCTION: At present whether to use T-tube or not during orthotopic liver
      transplantation (OLT) in biliary tract reconstruction still remains
      controversial. Most transplant centers choose not to use T-tube because the T
      tube can increase the incidence of cholangitis, but some centers still use T-tube
      because the T-tube can decrease the incidence of anastomotic strictures. AIM: The
      purpose of this study is to compare biliary complications after biliary tract
      reconstruction with or without T-tube in OLT. METHODS: systematic review and meta
      analysis of a collection of 15 studies (six randomized control trails (RCTs) and
      nine comparative studies) to compare biliary complications after biliary tract
      reconstruction with or without T-tube in OLT. RESULTS: The data showed that the
      biliary tract reconstruction with T-tube and without T-tube had equivalent
      outcomes for overall biliary complications (six RCTs p = 0.76; odd ratio [OR] =
      1.19; 95% CI: 0.40, 3.58; all studies p = 0.14; OR = 1.50; 95% CI: 0.88, 2.57),
      bile leaks (six RCTs p = 0.61; OR = 0.86; 95% CI: 0.49, 1.52; all studies p =
      0.09; OR = 1.39; 95% CI: 0.95, 2.02), cholangitis (six RCTs p = 0.13; OR = 5.54;
      95% CI: 0.62, 49.79; all studies p = 0.08; OR = 4.27; 95% CI: 0.86, 21.16),
      hepatic artery thrombosis (two RCTs p = 1.00; OR = 1.00; 95% CI: 0.22, 4.49; all
      studies p = 0.75; OR = 1.19; 95% CI: 0.41, 3.44). However, in the group with T
      tube there were better outcomes for biliary strictures (six RCTs p = 0.0003; OR =
      0.34; 95% CI: 0.19, 0.61; all studies p < 0.0001; OR = 0.49; 95% CI: 0.34, 0.69).
      DISCUSSION: Although most organizations choose not to use T-tube in OLT, we
      suggest that use of T-tube in biliary tract reconstruction during OLT for the
      recipients who possibly have high risks of biliary stricture is useful and
      necessary.

PMID- 25583037
TI  - In search for the many faces of community resilience among LGBT individuals.
AB  - Many countries (e.g., Egypt, Russia, and Uganda) have very draconian laws against
      LGBT individuals. Despite facing such adversity or hostility many LGBT
      individuals do strive and maintain their sense of self-worth. How do they do it?
      The collection of papers in this special issue attempts to provide some answers
      to this question. I will attempt to analyze two overlapping issues in these
      papers, and how they might inform LGBT research using a resilience lens. 

PMID- 25583038
TI  - Ebola's media outbreak: lessons for the future.

PMID- 25583039
TI  - The Ebola crisis: perspectives from European Public Health.

PMID- 25583040
TI  - Charlson index scores from administrative data and case-note review compared
      favourably in a renal disease cohort.
AB  - BACKGROUND: The Charlson index is a widely used measure of comorbidity. The
      objective was to compare Charlson index scores calculated using administrative
      data to those calculated using case-note review (CNR) in relation to all-cause
      mortality and initiation of renal replacement therapy (RRT) in the Grampian
      Laboratory Outcomes Mortality and Morbidity Study (GLOMMS-1) chronic kidney
      disease cohort. METHODS: Modified Charlson index scores were calculated using
      both data sources in the GLOMMS-1 cohort. Agreement between scores was assessed
      using the weighted Kappa. The association with outcomes was assessed using
      Poisson regression, and the performance of each was compared using net
      reclassification improvement. RESULTS: Of 3382 individuals, median age 78.5
      years, 56% female, there was moderate agreement between scores derived from the
      two data sources (weighted kappa 0.41). Both scores were associated with
      mortality independent of a number of confounding factors. Administrative data
      Charlson scores were more strongly associated with death than CNR scores using
      net reclassification improvement. Neither score was associated with commencing
      RRT. CONCLUSION: Despite only moderate agreement, modified Charlson index scores
      from both data sources were associated with mortality. Neither was associated
      with commencing RRT. Administrative data compared favourably and may be superior
      to CNR when used in the Charlson index to predict mortality.

PMID- 25583041
TI  - The next critical role of orthopedic registries.

PMID- 25583042
TI  - Drug utilization pattern in children and off-label use of medicines in a
      pediatric intensive care unit.
AB  - OBJECTIVE: This study aims to assess the prescription profile and license status
      of drugs used in a neonatal and pediatric intensive care unit (NPICU). METHODS: A
      prospective observational study was conducted on a dynamic cohort of children
      admitted to an NPICU (N=81) in a tertiary hospital (Granada, Spain). All
      prescriptions were classified as off-label or unlicensed based on the summary of
      product characteristics (SPC). RESULTS: Of a total of 601 prescriptions, the
      patients received a mean of 7.4 +/- 6 drugs each. The most commonly prescribed
      drugs corresponded to classes J (anti-infectious, systemic use) N (nervous
      system) and C (cardiovascular). A little over one-half of the prescriptions were
      off-label (52%), usually due to dosages differing from the SPC recommendations
      (79%), followed by different indications (13.5%), age (5%) and administration
      route (2.5%). In this NPICU, unlicensed usage represented only 5% of all
      prescriptions. CONCLUSIONS: This study contributes data on prescription of this
      kind in a Spanish NPICU, revealing at least one off-label prescription in 89% of
      the children and at least one unlicensed use in 22.3%. These are high figures,
      but are to be expected given the inclusion of newborn infants and the critical
      care setting. Even though such usage follows clinical protocols, we underscore
      the dual need to base treatment on the best available evidence, and to upgrade
      the SPC accordingly.

PMID- 25583043
TI  - [Hemoperfusion with activated charcoal on valproic acid poisoning. A case
      report].

PMID- 25583044
TI  - Transcranial Doppler ultrasound in the diagnosis of brain death. Is it useful or
      does it delay the diagnosis?
AB  - Transcranial Doppler ultrasound is able to demonstrate cerebral circulatory
      arrest associated to brain death, being especially useful in sedated patients, or
      in those in which complete neurological exploration is not possible. Transcranial
      Doppler ulstrasound is a portable, noninvasive and high-availability technique.
      Among its limitations, mention must be made of the absence of acoustic windows
      and false-negative cases. In patients clinically diagnosed with brain death, with
      open skulls or with anoxia as the cause of death, cerebral blood flow can be
      observed by ultrasound, since cerebral circulatory arrest is not always
      synchronized to the clinical diagnosis. The diagnostic rate is therefore time
      dependent, and this fact that must be recognized in order to avoid delays in
      death certification. Despite its limitations, transcranial Doppler ulstrasound
      helps solve common diagnostic problems, avoids the unnecessary consumption of
      resources, and can optimize organ harvesting for transplantation. 

PMID- 25583045
TI  - [Severe respiratory failure and neuromuscular blockade after administration of
      colimycin].

PMID- 25583046
TI  - Contrast-enhanced signs of cardiac arrest during CT.

PMID- 25583047
TI  - Trends in Arteriovenous Fistula Use at Dialysis Initiation After Automated eGFR
      Reporting.
AB  - The purpose of this study was to examine trends in the presence of an
      arteriovenous fistula (AVF) at dialysis initiation before and after eGFR
      reporting. All incident dialysis patients from four Canadian provinces that
      implemented province-wide, automated laboratory reporting of eGFR with known
      vascular access at dialysis initiation were included in the study (N = 25,201)
      from 2001 to 2010. The primary outcome was the change in proportion of patients
      with an AVF at dialysis initiation using an interrupted time series and adjusted
      multilevel logistic regression models. AVF usage at dialysis initiation decreased
      gradually over the study period from 19.0% to 14.6%. After implementation of
      automated eGFR reporting, there was attenuation in the decline in AVF usage in
      models adjusted for case-mix, facility, and the downward trajectory in AVF use
      over time. The adjusted odds ratio for initiating dialysis with an AVF 1 year
      post-eGFR reporting compared to pre-eGFR reporting was more pronounced in older
      patients (age tertile >73; OR: 1.40; 95% CI: 1.04-1.90). Laboratory-based eGFR
      reporting was associated with a possible attenuation in the decline of AVF at
      dialysis initiation and this was more pronounced in older patients. 

PMID- 25583049
TI  - pH-regulated selectivity in supramolecular polymerizations: switching between Co-
      and homopolymers.
AB  - A strategy is presented to regulate the selectivity in aqueous supramolecular
      polymerizations by changes in pH. In neutral buffered conditions, oppositely
      charged phenylalanine-based dendritic peptide amphiphiles self-assemble into (A
      B)n alternating copolymers of low polydispersity when mixed in a 1:1 comonomer
      feed ratio. Via pH switch of the glutamic acid and lysine side chains, attractive
      Coulomb interactions in the coassembled materials are screened and selective
      polymerization occurs to form (A)n homopolymers of the acidic comonomer at low pH
      and (B)n homopolymers of the basic comonomer at high pH, while the complementary
      comonomer is released during the transition. Reversible switching is demonstrated
      between these three different polymeric states, which were characterized by CD
      and fluorescence spectroscopy, using a peptide based minimalistic
      fluorophore/quencher pair, and transmission electron microscopy.

PMID- 25583048
TI  - Human native, enzymatically modified and oxidized low density lipoproteins show
      different lipidomic pattern.
AB  - In the present paper we have performed comparative lipidomic analysis of two
      prototypic atherogenic LDL modifications, oxidized LDL and enzymatically modified
      LDL. Oxidization of LDL was carried out with different chemical modifications
      starting from the same native LDL preparations: (i) by copper oxidation leading
      to terminally oxidized LDL (oxLDL), (ii) by moderate oxidization with HOCl (HOCl
      LDL), (iii) by long term storage of LDL at 4 degrees C to produce minimally
      modified LDL (mmLDL), or (iv) by 15-lipoxygenase, produced by a transfected
      fibroblast cell line (LipoxLDL). The enzymatic modification of LDL was performed
      by treatment of native LDL with trypsin and cholesteryl esterase (eLDL). Free
      cholesterol (FC) and cholesteryl esters (CE) represent the predominant lipid
      classes in all LDL preparations. In contrast to native LDL, which contains about
      two-thirds of total cholesterol as CE, enzymatic modification of LDL decreased
      the proportion of CE to about one-third. Free cholesterol and CE in oxLDL are
      reduced by their conversion to oxysterols. Oxidization of LDL preferentially
      influences the content of polyunsaturated phosphatidylcholine (PC) and
      polyunsaturated plasmalogen species, by reducing the total PC fraction in oxLDL.
      Concomitantly, a strong rise of the lysophosphatidylcholine (LPC) fraction can be
      found in oxLDL as compared to native LDL. This effect is less pronounced in eLDL.
      The mild oxidation of LDL with hypochlorite and/or lipoxygenase does not alter
      the content of the analyzed lipid classes and species in a significant manner.
      The lipidomic characterization of modified LDLs contributes to the better
      understanding their diverse cellular effects. 

PMID- 25583050
TI  - Incidence of herpes zoster infections in juvenile idiopathic arthritis patients.
AB  - The risk of herpes zoster among patients with juvenile idiopathic arthritis (JIA)
      exposed to biologics has not been evaluated. We determined incidence rates of
      herpes zoster among children with JIA in correlation with medication at time of
      occurrence and total drug exposure. The German biologics register database was
      used to identify patients with herpes zoster. Crude infection rates and incidence
      ratios (IRR) were compared to published rates. Demographics and overall exposure
      and particular exposure time to corticosteroids, immunosuppressive drugs and
      biologics were analyzed. The JIA cohort included 3,042 patients with 5,557.9
      person-years of follow-up; 1,628 have used corticosteroids, 2,930 methotrexate
      and 1,685 etanercept. In total, 17 herpes zoster events have been documented
      [6/1,000 patients (3.5-9.0); 3.1/1,000 patient-years (1.9-4.9)]. Thus, the
      incidence rate in JIA patients was higher than expected [IRR 2.9 (1.8-4.5), p <
      0.001]. In all patients, the event resolved completely. There were two
      complications, one patient developed intercostal neuralgia, and one had a
      recurrent herpes zoster. Compared to the healthy population, a significant higher
      IRR is observed in JIA patients who received a monotherapy with etanercept or in
      combination with steroids and methotrexate, but not in JIA patients exposed to
      methotrexate without biologics. In comparison with our control group of patients
      treated with methotrexate, the IRR was higher for exposure to etanercept
      monotherapy and combination of etanercept and corticosteroids irrespective of
      methotrexate use. A generally higher incidence rate in JIA patients treated with
      etanercept was observed. No serious or refractory manifestations occurred. 

PMID- 25583052
TI  - Interpreting the Athlete's EKG: are all repolarization anomalies created equal?

PMID- 25583051
TI  - Fibrofog and fibromyalgia: a narrative review and implications for clinical
      practice.
AB  - Patients with fibromyalgia often report forgetfulness as well as declines in
      cognitive function, memory, and mental alertness-symptoms that have been termed
      "fibrofog" in popular and electronic media as well as in professional literature.
      "Fibrofog" is the subjectively experienced cognitive dysfunction associated with
      fibromyalgia and is a clinically important yet comparatively less well-studied
      aspect of the disorder; it includes loss of mental clarity (mental fogginess) as
      well as attention and memory impairment. Although until recently cognitive
      symptoms have been largely ignored, these symptoms can be more disturbing than
      the widespread pain and can change these patients' lives, sometimes dramatically
      so. Whereas widespread musculoskeletal pain, tenderness, and fatigue may be the
      hallmark symptoms of fibromyalgia, patients rank cognitive dysfunction highly in
      terms of disease impact. This review addresses (1) the prevalence of self
      reported cognitive disturbances in fibromyalgia, (2) the clinical presentation of
      fibrofog, (3) neuropsychological test performance, with particular attention to
      discrepancies between self-report and test results, (3) clinical correlates of
      impaired cognitive function in fibromyalgia, (4) neurobiology relevant to
      cognitive disturbances in fibromyalgia, and (5) clinical management of fibrofog.
      Although the pathophysiology of fibromyalgia remains an enigma, evidence suggests
      that it may be a brain disorder, with cognitive deficits ("fibrofog") reflecting
      disturbed centrally mediated processes. 

PMID- 25583054
TI  - Clinical evaluation and management of pulmonary hypertension in the adult with
      congenital heart disease.

PMID- 25583055
TI  - ECG Response: January 13, 2015.

PMID- 25583053
TI  - Recognition and significance of pathological T-wave inversions in athletes.
AB  - BACKGROUND: Pathological T-wave inversion (PTWI) is rarely observed on the ECG of
      healthy athletes, whereas it is common in patients with certain cardiac diseases.
      All ECG interpretation guidelines for use within athletes state that PTWI (except
      in leads aVR, III and V1 and in V1-V4 when preceded by domed ST segment in
      asymptomatic Afro-Caribbean athletes only) cannot be considered a physiological
      adaptation. The aims of the present study were to prospectively determine the
      prevalence of cardiac pathology in athletes presenting with PTWI, and to examine
      the efficacy of cardiac magnetic resonance in the work-up battery of further
      examinations. METHODS AND RESULTS: Athletes presenting with PTWI (n=155) were
      investigated with clinical examination, ECG, echocardiography, exercise testing,
      24h Holter ECG, and cardiac magnetic resonance. Cardiac disease was established
      in 44.5% of athletes, with hypertrophic cardiomyopathy (81%) the most common
      pathology. Echocardiography was abnormal in 53.6% of positive cases, and cardiac
      magnetic resonance identified a further 24 athletes with disease. Five athletes
      (7.2%) considered normal on initial presentation subsequently expressed pathology
      during follow-up. Familial history of sudden cardiac death and ST-segment
      depression associated with PTWI were predictive of cardiac disease. CONCLUSIONS:
      PTWI should be considered pathological in all cases until proven otherwise,
      because it was associated with cardiac pathology in 45% of athletes. Despite
      echocardiography identifying pathology in half of these cases, cardiac magnetic
      resonance must be considered routine in athletes presenting with PTWI with normal
      echocardiography. Although exclusion from competitive sport is not warranted in
      the presence of normal secondary examinations, annual follow-up is essential to
      ascertain possible disease expression.

PMID- 25583056
TI  - Subepicardial hematoma of the left ventricle mimicking acute anterior myocardial
      infarction.

PMID- 25583057
TI  - Aorto-left ventricular tunnel in a multianeurysmal heart.

PMID- 25583058
TI  - Letter by Iqbal and Serruys regarding article, "postprocedural aortic
      regurgitation in balloon-expandable and self-expandable transcatheter aortic
      valve replacement procedures: analysis of predictors and impact on long-term
      mortality: insights from the FRANCE2 registry".

PMID- 25583059
TI  - Response to letter regarding article, "postprocedural aortic regurgitation in
      balloon-expandable and self-expandable transcatheter aortic valve replacement
      procedures: analysis of predictors and impact on long-term mortality: insights
      from the FRANCE2 registry".

PMID- 25583060
TI  - Letter by Hugenholtz and Lisman regarding article, "plasmin cleavage of von
      Willebrand factor as an emergency bypass for ADAMTS13 deficiency in thrombotic
      microangiopathy".

PMID- 25583061
TI  - Response to letter regarding article, "plasmin cleavage of von willebrand factor
      as an emergency bypass for ADAMTS13 deficiency in thrombotic microangiopathy".

PMID- 25583062
TI  - Association between vitamin B12 deficiency and long-term use of acid-lowering
      agents: a systematic review and meta-analysis.
AB  - BACKGROUND: Vitamin B12 (cobalamin) deficiency can result in irreversible
      structural brain changes if not treated appropriately. Long-term use of acid
      lowering agents (ALA) has been linked to vitamin B12 deficiency, but results are
      inconsistent. AIM: To evaluate the association between prolonged ALA use and
      vitamin B12 deficiency by performing a meta-analysis. METHODS: A systematic
      search was conducted using MEDLINE, PubMed, EMBASE, Current Contents, Cochrane
      Library, Google Scholar, Science Direct and Web of Science. Original data were
      abstracted from each study and used to calculate a pooled odds ratio and 95%
      confidence interval (95% CI). RESULTS: Of the articles reviewed, four case
      control studies (4254 cases and 19,228 controls) and one observational study met
      full criteria for analysis. The long-term ALA use was significantly associated
      with development of vitamin B12 deficiency (hazard ratio 1.83, 95% CI: 1.36-2.46,
      P-value 0.00). CONCLUSION: Chronic use of ALA is a risk factor for developing
      vitamin B12 deficiency. Judicious prescribing of ALA and regular monitoring of
      vitamin B12 in patients who are inevitably on long-term ALA therapy are
      recommended.

PMID- 25583063
TI  - New insight into the atomic-scale bulk and surface structure evolution of
      Li4Ti5O12 anode.
AB  - Identifying the structure of electrodes at atomic-scale remains a key challenge
      but is a fertile realm for groundbreaking fundamental research in the advanced Li
      ion battery material field. In this context, the subtle structure evolution
      taking place during lithiation/delithiation in the bulk/surface of
      Li(4)Ti(5)O(12) spinel (LTO) was probed using scanning transmission electron
      microscopy and found to undergo significant structure torque, namely Ti-O bond
      stretching/shrinking at different state-of-charge (SOC), which is not identified
      previously. This kind of nanostructure change plays an important role in
      facilitating the formation of capturing centers for the electron/hole pairs in a
      3.80 eV insulating material as is LTO. Furthermore, with the aid of electron
      energy loss spectroscopy, the spontaneous charge transfer process, Ti(3+) <-> e(
      ) + Ti(4+), was confirmed in the fully lithiated Li(7)Ti(5)O(12) surface as an
      essential step of the gas-releasing phenomenon. This new insight paves the way
      toward deeper comprehension and ultimately control of the electrochemical process
      for this and other important Li-ion battery materials.

PMID- 25583064
TI  - Local perception of infrequent, extreme upland flash flooding: prisoners of
      experience?
AB  - The United Kingdom has experienced several exceptional summer flash floods in
      recent years and there is growing concern about the frequency of such events and
      the preparedness of the population. This paper uses a case study of the upper
      Ryedale flash flood (2005) and questionnaire and interview data to assess local
      perceptions of upland flash flooding. Experience of a major flash flood may not
      be associated with increased flood risk perception. Despite local residents'
      awareness of a trend towards wetter summers and more frequent heavy rainfall, the
      poor maintenance of rivers was more frequently thought to be a more significant
      factor influencing local flood risk than climate change. Such findings have
      important implications for the potential success of contemporary national flood
      policies, which have put greater emphasis on public responsibility for responding
      to flooding. This study recommends, therefore, the use of fresh participatory
      approaches to redistribute and raise awareness of locally-held flood knowledge. 

PMID- 25583065
TI  - From the fax machine to the digital age: reflections on JSPN's coming of age.

PMID- 25583066
TI  - Laser-ablation production of graphene oxide nanostructures: from ribbons to
      quantum dots.
AB  - A new one-step method for the preparation of graphene oxide (GO) nanostructures
      has been developed by pulsed laser ablation in GO solution. The formation of
      different shapes of GO nanostructures, such as ribbons, nanoflakes (including
      nano-squares, nano-rectangles, nano-triangles, nano-hexagons, and nano-disks) and
      quantum dots, has been demonstrated by scanning electron microscopy and
      transmission electron microscopy. Photoreduction for the GO occurred during
      irradiation by the pulsed laser. The GO quantum dots exhibit a blue
      photoluminescence, originating from recombination of the localized carriers in
      the zigzag-edge states. 

PMID- 25583067
TI  - Inter-specific variation in headspace scent volatiles composition of four
      commercially cultivated jasmine flowers.
AB  - Jasmines are commercially grown for their fragrant flowers and essential oil
      production. The flowers of jasmine emit sweet-smelling fragrance from evening
      till midnight. This study was designed to study the composition and inter
      specific variation of the emitted scent volatiles from flowers of four
      commercially cultivated Jasminum species namely, Jasminum sambac, Jasminum
      auriculatum, Jasminum grandiflorum and Jasminum multiflorum. Gas chromatography
      mass spectrometry analysis revealed that the scent volatiles composition of these
      flowers was predominantly enriched with both terpenoid and benzenoid compounds.
      Linalool and (3E,6E)-alpha-farnesene were identified as the major monoterpene and
      sesquiterpene in all the four species, respectively. The most abundant benzenoid
      detected in all flowers was benzyl acetate. Comparison of volatile profiles
      indicated a variation in fragrance contents and types emitted from these four
      jasmine flowers. The outcome of this study shall help in elucidating the enzymes
      and genes of fragrance biosynthesis in jasmines and in aiming to create flowers
      with improved scent quality. 

PMID- 25583068
TI  - Facile and sensitive glucose sandwich assay using in situ-generated Raman
      reporters.
AB  - A facile and sensitive glucose sandwich assay using surface-enhanced Raman
      scattering (SERS) has been developed through the use of the self-assembled p
      mercaptophenylboronic acid (PMBA) monolayer on a smooth gold-coated slide and the
      SERS tags of Ag nanoparticles (AgNPs) modified with p-aminothiophenol (PATP) and
      PMBA. The photocoupling product 4,4'-dimercaptoazobenzene (DMAB), generated in
      situ from PATP on the AgNP surface during the SERS measurement, possessed
      considerably intense characteristic SERS peaks and acted as the actual Raman
      reporter, which improved the sensitivity of glucose detection devoid of
      interference of other biomolecules. The facile sandwich assay showed a high
      selectivity of glucose over fructose and galactose. This facile, sensitive, and
      selective SERS-based glucose sandwich assay can be developed into a diagnostic
      tool for determination of glucose levels. 

PMID- 25583069
TI  - Host life history and host-parasite syntopy predict behavioural resistance and
      tolerance of parasites.
AB  - There is growing interest in the role that life-history traits of hosts, such as
      their 'pace-of-life', play in the evolution of resistance and tolerance to
      parasites. Theory suggests that, relative to host species that have high syntopy
      (local spatial and temporal overlap) with parasites, host species with low
      syntopy should have lower selection pressures for more constitutive (always
      present) and costly defences, such as tolerance, and greater reliance on more
      inducible and cheaper defences, such as behaviour. Consequently, we postulated
      that the degree of host-parasite syntopy, which is negatively correlated with
      host pace-of-life (an axis reflecting the developmental rate of tadpoles and the
      inverse of their size at metamorphosis) in our tadpole-parasitic cercarial
      (trematode) system, would be a negative and positive predictor of behavioural
      resistance and tolerance, respectively. To test these hypotheses, we exposed
      seven tadpole species to a range of parasite (cercarial) doses crossed with
      anaesthesia treatments that controlled for anti-parasite behaviour. We quantified
      host behaviour, successful and unsuccessful infections, and each species'
      reaction norm for behavioural resistance and tolerance, defined as the slope
      between cercarial exposure (or attempted infections) and anti-cercarial
      behaviours and mass change, respectively. Hence, tolerance is capturing any cost
      of parasite exposure. As hypothesized, tadpole pace-of-life was a significant
      positive predictor of behavioural resistance and negative predictor of tolerance,
      a result that is consistent with a trade-off between behavioural resistance and
      tolerance across species that warrants further investigation. Moreover, these
      results were robust to considerations of phylogeny, all possible re-orderings of
      the three fastest or slowest paced species, and various measurements of
      tolerance. These results suggest that host pace-of-life and host-parasite syntopy
      are powerful drivers of both the strength and type of host defence strategies
      against parasites. Future research should evaluate how often and how strongly
      host pace-of-life and host-parasite syntopy are correlated and which is the
      better predictor of the strength and type of host investments in anti-parasite
      defences. 

PMID- 25583070
TI  - A novel function for Egr4 in posterior hindbrain development.
AB  - Segmentation of the vertebrate hindbrain is an evolutionarily conserved process.
      Here, we identify the transcription factor early growth response 4 (egr4) as a
      novel regulator of posterior hindbrain development in Xenopus. egr4 is
      specifically and transiently expressed in rhombomeres 5 and 6 (r5/r6), and Egr4
      knockdown causes a loss of mafb/kreisler and krox20/egr2 expression in r5/r6 and
      r5, respectively. This phenotype can be fully rescued by injection of frog or
      mouse Egr4 mRNA. Moreover Egr4-depleted embryos exhibit a specific loss of the
      neural crest stream adjacent to r5, and have inner ear defects. While the
      homeodomain protein vHnf1/Hnf1b directly activates Mafb and Krox20 expression in
      the mouse hindbrain to specify r5, we show that in Xenopus this process is
      indirect through the activation of Egr4. We provide evidence that rearrangements
      in the regulatory sequences around egr4 and mafb genes may account for this
      difference. 

PMID- 25583071
TI  - Degradation of gap junction connexins is regulated by the interaction with Cx43
      interacting protein of 75 kDa (CIP75).
AB  - Connexins are a family of transmembrane proteins that form gap junction channels.
      These proteins undergo both proteasomal and lysosomal degradation, mechanisms
      that serve to regulate connexin levels. Our previous work described CIP75
      [connexin43 (Cx43)-interacting protein of 75 kDa], a protein involved in
      proteasomal degradation, as a novel Cx43-interacting protein. We have discovered
      two additional connexins, connexin40 (Cx40) and connexin45 (Cx45), that interact
      with CIP75. Nuclear magnetic resonance (NMR) analyses identified the direct
      interaction of the CIP75 UBA domain with the carboxyl-terminal (CT) domains of
      Cx40 and Cx45. Reduction in CIP75 by shRNA in HeLa cells expressing Cx40 or Cx45
      resulted in increased levels of the connexins. Furthermore, treatment with
      trafficking inhibitors confirmed that both connexins undergo endoplasmic
      reticulum-associated degradation (ERAD), and that CIP75 preferentially interacts
      with the connexin proteins bound for proteasomal degradation from the ER. In
      addition, we have also discovered that CIP75 interacts with ER-localized Cx32 in
      a process that is likely mediated by Cx32 ubiquitination. Thus, we have
      identified novel interacting connexin proteins of CIP75, indicating a role for
      CIP75 in regulating the levels of connexins in general, through proteasomal
      degradation. 

PMID- 25583073
TI  - Novel phospholipase A2 inhibitors from python serum are potent peptide
      antibiotics.
AB  - Antimicrobial peptides (AMPs) play a vital role in defense against resistant
      bacteria. In this study, eight different AMPs synthesized from Python reticulatus
      serum protein were tested for bactericidal activity against various Gram-positive
      and Gram-negative bacteria (Staphylococcus aureus, Burkholderia pseudomallei (KHW
      and TES strains), and Proteus vulgaris) using a disc-diffusion method (20
      MUg/disc). Among the tested peptides, phospholipase A2 inhibitory peptide (PIP)
      18[59-76], beta-Asp65-PIP[59-67], D-Ala66-PNT.II, and D60,65E-PIP[59-67]
      displayed the most potent bactericidal activity against all tested pathogens in a
      dose-dependent manner (100-6.8 MUg/ml), with a remarkable activity noted against
      S. aureus at 6.8 MUg/ml dose within 6 h of incubation. Determination of minimum
      inhibitory concentrations (MICs) by a micro-broth dilution method at 100-3.125
      MUg/ml revealed that PIP-18[59-76], beta-Asp65-PIP[59-67] and D-Ala66-PNT.II
      peptides exerted a potent inhibitory effect against S. aureus and B. pseudomallei
      (KHW) (MICs 3.125 MUg/ml), while a much less inhibitory potency (MICs 12.5
      MUg/ml) was noted for beta-Asp65-PIP[59-67] and D-Ala66-PNT.II peptides against
      B. pseudomallei (TES). Higher doses of peptides had no effect on the other two
      strains (i.e., Klebsiella pneumoniae and Streptococcus pneumoniae). Overall, PIP
      18[59-76] possessed higher antimicrobial activity than that of chloramphenicol
      (CHL), ceftazidime (CF) and streptomycin (ST) (30 MUg/disc). When the two most
      active peptides, PIP-18[59-76] and beta-Asp65-PIP[59-67], were applied topically
      at a 150 mg/kg dose for testing wound healing activity in a mouse model of S.
      aureus infection, the former accelerates faster wound healing than the latter
      peptide at 14 days post-treatment. The western blot data suggest that the topical
      application of peptides (PIP-18[59-67] and beta-Asp65-PIP[59-67]) modulates NF-kB
      mediated wound repair in mice with relatively little haemolytic (100-1.56 MUg/ml)
      and cytotoxic (1000-3.125 MUg/ml) effects evident on human cells in vitro.

PMID- 25583072
TI  - Comparative genomic analysis of evolutionarily conserved but functionally
      uncharacterized membrane proteins in archaea: Prediction of novel components of
      secretion, membrane remodeling and glycosylation systems.
AB  - A systematic comparative genomic analysis of all archaeal membrane proteins that
      have been projected to the last archaeal common ancestor gene set led to the
      identification of several novel components of predicted secretion, membrane
      remodeling, and protein glycosylation systems. Among other findings, most
      crenarchaea have been shown to encode highly diverged orthologs of the membrane
      insertase YidC, which is nearly universal in bacteria, eukaryotes, and
      euryarchaea. We also identified a vast family of archaeal proteins, including the
      C-terminal domain of N-glycosylation protein AglD, as membrane flippases
      homologous to the flippase domain of bacterial multipeptide resistance factor
      MprF, a bifunctional lysylphosphatidylglycerol synthase and flippase.
      Additionally, several proteins were predicted to function as membrane
      transporters. The results of this work, combined with our previous analyses,
      reveal an unexpected diversity of putative archaeal membrane-associated
      functional systems that remain to be functionally characterized. A more general
      conclusion from this work is that the currently available collection of archaeal
      (and bacterial) genomes could be sufficient to identify (almost) all widespread
      functional modules and develop experimentally testable predictions of their
      functions. 

PMID- 25583074
TI  - Pericardial effusion following drain removal after percutaneous epicardial access
      for an electrophysiology procedure.
AB  - OBJECTIVES: To determine the frequency and predictors of pericardial effusion
      following epicardial sheath removal. BACKGROUND: Pericardial effusion can occur
      following cardiac surgical or interventional procedures including percutaneous
      epicardial access (EpiAcc), which is increasingly used as part of
      electrophysiology ablation procedures. METHODS: A retrospective analysis of the
      Mayo Clinic comprehensive electronic medical record was performed from all
      patients who underwent planned EpiAcc as part of an electrophysiology ablation
      procedure between January 1, 2004 and June 30, 2013. RESULTS: Of 144 patients
      (mean age 51.3 +/- 15.5 years, 68% male) who underwent planned EpiAcc as part of
      an electrophysiology ablation (95.8% pericardial access success rate), seven
      (4.9%) developed a postoperative pericardial effusion requiring repeat EpiAcc.
      Inferior access was utilized in 74 (51.4%) patients. Patients with pericardial
      effusion tended to be younger (41.1 years vs 51.8 years, P = 0.08) and were more
      likely to have undergone inferior approach access (85.7% vs 49.6%, P = 0.06) than
      those who did not develop postoperative pericardial effusion. Seventy-one percent
      of patients with postoperative pericardial effusion versus 32.1% of patients
      without postoperative pericardial effusion had a preprocedure ejection fraction
      >=55% (P = 0.03). There were no procedural-related deaths, and no difference in
      mortality between groups. CONCLUSIONS: Postoperative pericardial effusion
      requiring repeat access/drainage was relatively infrequent, occurring in 4.9% of
      patients shortly after epicardial procedures. While the majority occur early and
      therefore require close observation, some patients may present in a delayed
      manner.

PMID- 25583076
TI  - Metabolomics analysis of soy hydrolysates for the identification of productivity
      markers of mammalian cells for manufacturing therapeutic proteins.
AB  - Soy hydrolysates are widely used as a nutrient supplement in mammalian cell
      culture for the production of recombinant proteins. The batch-to-batch
      variability of a soy hydrolysate often leads to productivity differences. This
      report describes our metabolomics platform, which includes a battery of LC-MS/MS
      modes of operation, and advanced data analysis software for automated data
      processing. The platform was successfully used for screening productivity markers
      in soy hydrolysates during the production of two therapeutic antibodies in two
      Chinese hamster ovary cell lines. A total of 123 soy hydrolysate batches were
      analyzed, from which 62 batches were used in the production runs of cell line #1
      and 12 batches were used in the production runs of cell line #2. For cell line
      #1, out of 19 amino acids, 106 other metabolites and 4,131 peptides identified in
      the soy hydrolysate batches being used, several nucleosides and short hydrophobic
      peptides showed negative correlation with antibody titer, while ornithine,
      citrulline and several amino acids and organic acids correlated positively with
      titer. For cell line #2, only ornithine and citrulline showed strong positive
      correlation. When ornithine was spiked into the culture media, both cell lines
      demonstrated accelerated cell growth, indicating ornithine as a root cause of the
      performance difference. It is proposed that better soy hydrolysate performance
      resulted from better bacterial fermentation during the hydrolysate production. A
      few selected markers were used to predict the performance of other soy
      hydrolysate batches for cell line #1. The predicted titers agreed with the
      experimental values with good accuracy.

PMID- 25583077
TI  - Motion analysis of U11 to U16 elite English Premier League Academy players.
AB  - This study examined (1) the distances and speeds covered during match play for
      U11 to U16 English Premier League Academy players, (2) the differences in match
      performance between retained and released players and (3) the effect of
      calculating speed zones in different ways when analysing match performance.
      Eighty-one academy outfield players (10-16 years old), competing in 11-a-side
      matches, were analysed using a 1-Hz global positioning system with three speed
      zones (absolute, squad and individual). Pitch dimensions were 78.7 * 54.1 m (U11
      and U12), 88.0 * 64.2 m (U13) and 100.8 * 68.2 m (U14-U16). Match durations were
      20 min * 2 + 15 min * 2 or 25 min * 3 (U11), 25 min * 3 (U12 and U13) and 40 min
      * 2 (U14-U16). The matches were part of the regular series of inter-academy
      matches between Premier League Academies during a season. Completion of at least
      a half of the duration of a match in two separate matches (mean +/- s = 3.1 +/-
      0.8 matches; range: 2-4 matches) was the criterion for inclusion in the study.
      Total match running distance increased with age from ~5700 (U11) to ~6700 m . h(
      1) (U15) (P < 0.01). Using the absolute speed zones, it was possible to discern
      differences in high-intensity (>6.0 m . s(-1)) distance covered with age (U11: 29
      m . h(-1), U16: 164 m . h(-1), P < 0.01). Using the squad speed zones, it was
      possible to discern differences between retained and released players in the
      U11/U12s (moderate-speed running) and in the U15/U16s (walking, jogging and low
      speed running) (P < 0.01). Thus, total and high-intensity running distances
      increase with age, and walking, jogging, low-speed running and moderate-speed
      running distances are greater in retained than in released players and these
      differences are best identified through the use of absolute and squad speed
      zones, respectively. 

PMID- 25583078
TI  - In reply: Lingual traction to aid fiberoptic intubation.

PMID- 25583079
TI  - Diabetic neuropathy: comparison between Bangladeshi immigrants and Greek-born
      subjects.
AB  - The aim of this study was to compare Bangladeshi immigrants with diabetes to
      native Greeks with diabetes and to distinguish the different risk factors for
      polyneuropathy (PN) in the two ethnic groups. Subjects were recruited from the
      outpatient diabetic clinic of a general hospital. A total of 111 Bangladeshi
      immigrants (97 men and 14 women of mean age 47 years) and 101 native Greeks (82
      men and 19 women of mean age 49 years) were included in the study. Sex, mean age,
      age at diabetes diagnosis, and diabetes duration did not differ between the two
      groups. PN was diagnosed in 53 (48%) Bangladeshi and in 59 (58%) Greek patients
      (p = 0.12). Large fiber neuropathy was less prevalent among Bangladeshis (18%)
      than in Greeks (53%) (p < 0.01). Small fiber neuropathy on the contrary were more
      frequent in Bangladeshis (18% vs. 7%) (p < 0.02). Regarding the risk factors for
      PN, Greek patients were taller, with higher BMI, and smoked more cigarettes (p <
      0.001). They were also treated with more anti-lipid and antihypertensive agents.
      The higher percentage of SFN in Bangladeshi was mainly a result of the
      significantly greater incidence of erectile dysfunction (ED) in their group (68
      Bangladeshi vs. 38 Greek men). It is well known that there are many causes of ED
      aside from SFN which were not evaluated in this study. Thus this conclusion
      should be taken with caution.

PMID- 25583080
TI  - Direct C-H arene homocoupling over gold nanoparticles supported on metal oxides.
AB  - The direct C?H/C?H bond coupling of dimethyl phthalate was performed successfully
      over supported gold nanoparticle catalysts. Gold on reducible metal oxides, such
      as Co3 O4 , and on inert oxides that have an oxygen-releasing capacity, such as
      ZrO2 , showed the highest catalytic activity for the production of biphenyl
      tetracarboxylate using O2 as the sole oxidant. Supported Pd(OH)2 also catalyzed
      the reaction, but the catalytic activity was inferior to that of gold. Moreover,
      the gold catalysts exhibited excellent regioselectivity for the synthesis of
      valuable 3,3',4,4'-tetrasubstituted biphenyls by coupling with each other at the
      4-position without the need for additional ligands. Gold catalysts also promoted
      the oxidative homocoupling of arenes including o-xylene to give symmetrical
      biaryls with high regioselectivity. X-ray absorption fine structure measurements
      revealed that the catalytically active species was Au(0) and that the lattice
      oxygen of Co3 O4 played an important role in the gold-catalyzed oxidative
      coupling. The results of the kinetic studies were consistent with an
      electrophilic aromatic substitution pathway. Regioselectivity is not controlled
      by directing groups or the electronic character of the substituents but by steric
      hindrance, which suggests that gold nanoparticles not only catalyze the oxidative
      coupling but also act as bulky ligands to control the regioselectivity. 

PMID- 25583081
TI  - Corrigendum for "Dissecting genetic effects with imprinting".
AB  - [This corrects the article DOI: 10.3389/fevo.2014.00051.][This corrects the
      article on p. 198 in vol. 5, PMID: 25071828.]. 

PMID- 25583082
TI  - Impact of a structured intern education programme on clinical documentation in
      the emergency department.
AB  - OBJECTIVES: To evaluate the impact of More Learning for Interns in Emergency
      (MoLIE) on clinical documentation in the ED of a large regional hospital.
      METHODS: MoLIE was implemented at The Townsville Hospital (TTH) in 2010, and has
      since provided ED interns with structured off-floor teaching and a dedicated
      clinical supervisor. A pre- and post-intervention study was conducted using
      retrospective medical record review methodology. Charts were selected by
      identifying all TTH ED patients seen by interns in the period 2008-2011. Two
      hundred pre-intervention records (2008-2009) and 200 post-intervention records
      (2010-2011) were reviewed. These were randomly selected following an initial
      screen by an ED staff specialist. The quality of clinical documentation for five
      common ED presentations (asthma, chest pain, lacerations, abdominal pain and
      upper limb fractures) was assessed. For each presentation, documentation quality
      was scored out of 10 using predefined criteria. An improvement of two or more was
      thought to be clinically significant. Mean scores for each group were compared
      using a Student's t-test for independent samples. RESULTS: Mean documentation
      scores (and 95% confidence intervals) were 5.55 (5.17-5.93) in 2008, 5.42 (4.98
      5.86) in 2009, 6.37 (5.99-6.75) in 2010 and 6.08 (5.71-6.45) in 2011. There was a
      statistically but not clinically significant improvement in scores pre- and post
      intervention (P <= 0.001). CONCLUSION: The introduction of MoLIE was associated
      with a small but statistically significant improvement in documentation, despite
      an 80% increase in intern placements. These results suggest that structured
      training programmes have potential to improve intern performance while
      simultaneously enhancing training capacity. The impact on quality of care
      requires further evaluation.

PMID- 25583083
TI  - Structural domains underlying the activation of acid-sensing ion channel 2a.
AB  - The acid-sensing ion channels (ASICs) are a family of ion channels expressed
      throughout the mammalian nervous system. The principal activator of ASICs is
      extracellular protons, and ASICs have been demonstrated to play a significant
      role in many physiologic and pathophysiologic processes, including synaptic
      transmission, nociception, and fear. However, not all ASICs are proton-sensitive:
      ASIC2a is activated by acid, whereas its splice variant ASIC2b is not. We made a
      series of chimeric ASIC2 proteins, and using whole-cell electrophysiology we have
      identified the minimal region of the ASIC2a extracellular domain that is required
      for ASIC2 proton activation: the first 87 amino acids after transmembrane domain
      1. We next examined the function of different domains within the ASIC2b N
      terminus and identified a region proximal to the first transmembrane domain that
      confers tachyphylaxis upon ASIC2a. We have thus identified domains of ASIC2 that
      are crucial to channel function and may be important for the function of other
      members of the ASIC family. 

PMID- 25583084
TI  - Dehydrocrenatidine is a novel janus kinase inhibitor.
AB  - Janus kinase (JAK) 2 plays a pivotal role in the tumorigenesis of signal
      transducers and activators of transcription (STAT) 3 constitutively activated
      solid tumors. JAK2 mutations are involved in the pathogenesis of various types of
      hematopoietic disorders, such as myeloproliferative disorders, polycythemia vera,
      essential thrombocythemia, and primary myelofibrosis. Thus, small-molecular
      inhibitors targeting JAK2 are potent for therapy of these diseases. In this
      study, we screened 1,062,608 drug-like molecules from the ZINC database and 2080
      natural product chemicals. We identified a novel JAK family kinase inhibitor,
      dehydrocrenatidine, that inhibits JAK-STAT3-dependent DU145 and MDA-MB-468 cell
      survival and induces cell apoptosis. Dehydrocrenatidine represses constitutively
      activated JAK2 and STAT3, as well as interleukin-6-, interferon-alpha-, and
      interferon-gamma-stimulated JAK activity, and STAT phosphorylation, and
      suppresses STAT3 and STAT1 downstream gene expression. Dehydrocrenatidine
      inhibits JAKs-JH1 domain overexpression-induced STAT3 and STAT1 phosphorylation.
      In addition, dehydrocrenatidine inhibits JAK2-JH1 kinase activity in vitro.
      Importantly, dehydrocrenatidine does not show significant effect on Src
      overexpression and epidermal growth factor-induced STAT3 activation. Our results
      indicate that dehydrocrenatidine is a JAK-specific inhibitor. 

PMID- 25583086
TI  - Behavioral assessment of auditory processing disorder in children with non
      syndromic cleft lip and/or palate.
AB  - OBJECTIVE: Peripheral hearing disorders have been frequently described in
      children with non-syndromic cleft lip and/or palate (NSCL/P). However, auditory
      processing problems are rarely considered for children with NSCL/P despite their
      poor academic performance in general compared to their craniofacially normal
      peers. This study aimed to compare auditory processing skills, using behavioral
      assessment techniques, in school age children with and without NSCL/P. METHODS:
      One hundred and forty one Mandarin-speaking children with NSCL/P aged from 6.00
      to 15.67 years, and 60 age-matched, craniofacially normal children, were
      recruited. Standard hearing health tests were conducted to evaluate peripheral
      hearing. Behavioral auditory processing assessment included adaptive tests of
      temporal resolution (ATTR), and the Mandarin pediatric lexical tone and
      disyllabic-word picture identification test in noise (MAPPID-N). RESULTS: Age
      effects were found in children with cleft disorder but not in the control group
      for gap detection thresholds with ATTR narrow band noise in the across-channel
      stimuli condition, with a significant difference in test performance between the
      6 to 8 year group and 12 to 15 year group of children with NSCL/P. For MAPPID-N,
      the bilateral cleft lip and palate subgroup showed significantly poorer SNR-50%
      scores than the control group in the condition where speech was spatially
      separated from noise. Also, the cleft palate participants showed a significantly
      smaller spatial separation advantage for speech recognition in noise compared to
      the control group children. CONCLUSION: ATTR gap detection test results indicated
      that maturation for temporal resolution abilities was not achieved in children
      with NSCL/P until approximately 8 years of age compared to approximately 6 years
      for craniofacially normal children. For speech recognition in noisy environments,
      poorer abilities to use timing and intensity cues were found in children with
      cleft palate and children with bilateral cleft lip and palate compared to
      craniofacially normal children. Consequently, it is worthwhile to consider the
      potential for auditory processing disorder in when assessing the auditory status
      of children with NSCL/P.

PMID- 25583087
TI  - Red ear syndrome: literature review and a pediatric case report.
AB  - Red ear syndrome (RES) is characterized by recurrent unilateral or bilateral
      painful attacks of the external ear, accompanied by ear redness, burning, or
      warmth. Proposed etiologies of this rare condition include dysregulation of
      sympathetic outflow, upper cervical pathology, glossopharyngeal and trigeminal
      neuralgia, TMJ dysfunction, thalamic syndrome, and primary headache syndromes.
      Idiopathic cases also exist in the literature. Pediatric cases are particularly
      rare and more commonly associated with migraine. Given the various potential
      etiologies, no single treatment is effective in all cases. This paper summarizes
      the current understanding and management of RES, and describes a case of
      idiopathic pediatric RES. 

PMID- 25583085
TI  - Rapid throughput analysis demonstrates that chemicals with distinct seizurogenic
      mechanisms differentially alter Ca2+ dynamics in networks formed by hippocampal
      neurons in culture.
AB  - Primary cultured hippocampal neurons (HN) form functional networks displaying
      synchronous Ca(2+) oscillations (SCOs) whose patterns influence plasticity.
      Whether chemicals with distinct seizurogenic mechanisms differentially alter SCO
      patterns was investigated using mouse HN loaded with the Ca(2+) indicator fluo-4
      AM. Intracellular Ca(2+) dynamics were recorded from 96 wells simultaneously in
      real-time using fluorescent imaging plate reader. Although quiescent at 4 days in
      vitro (DIV), HN acquired distinctive SCO patterns as they matured to form
      extensive dendritic networks by 16 DIV. Challenge with kainate, a kainate
      receptor (KAR) agonist, 4-aminopyridine (4-AP), a K(+) channel blocker, or
      pilocarpine, a muscarinic acetylcholine receptor agonist, caused distinct changes
      in SCO dynamics. Kainate at <1 uM produced a rapid rise in baseline Ca(2+) (Phase
      I response) associated with high-frequency and low-amplitude SCOs (Phase II
      response), whereas SCOs were completely repressed with >1 uM kainate. KAR
      competitive antagonist CNQX [6-cyano-7-nitroquinoxaline-2,3-dione] (1-10 uM)
      normalized Ca(2+) dynamics to the prekainate pattern. Pilocarpine lacked Phase I
      activity but caused a sevenfold prolongation of Phase II SCOs without altering
      either their frequency or amplitude, an effect normalized by atropine (0.3-1 uM).
      4-AP (1-30 uM) elicited a delayed Phase I response associated with persistent
      high-frequency, low-amplitude SCOs, and these disturbances were mitigated by
      pretreatment with the KCa activator SKA-31 [naphtho[1,2-d]thiazol-2-ylamine].
      Consistent with its antiepileptic and neuroprotective activities, nonselective
      voltage-gated Na(+) and Ca(2+) channel blocker lamotrigine partially resolved
      kainate- and pilocarpine-induced Ca(2+) dysregulation. This rapid throughput
      approach can discriminate among distinct seizurogenic mechanisms that alter
      Ca(2+) dynamics in neuronal networks and may be useful in screening antiepileptic
      drug candidates. 

PMID- 25583088
TI  - The effect of lycopene on experimental myringosclerosis.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of lycopene on
      myringosclerosis development using histopathological and immunohistochemical
      analyses. METHODS: Fifty-six intact tympanic membranes of 28 guinea pigs were
      included in the study. Subjects were randomly divided into four groups
      (n=7/group). Group I (control group) did not receive any treatment after
      myringotomy. Group II (lycopene treatment after myringotomy) received oral
      lycopene (once daily at the same time, 10mg/kg, dissolved in water, administered
      with a catheter). The treatment lasted seven days. Group III (lycopene treatment
      before and after myringotomy), received lycopene treatment (same dose and route
      of administration) for seven days. Myringotomy was performed on day 8, and
      lycopene treatment was initiated immediately, and continued for seven days (same
      dose and route of administration). Group IV (lycopene treatment before
      myringotomy) received lycopene treatment one week before myringotomy using the
      same method and dose for seven days. Myringotomy was performed on day 8. Lycopene
      was not administered after myringotomy. Fourteen days after myringotomy,
      myringosclerosis was evaluated automicroscopically and scored. Following
      decapitation, bulla were removed and immersed in a 10% formaldehyde solution.
      Sections were cut for histopathological and immunohistochemical examination, and
      thickness, sclerosis, inflammation, and collagen-IV accumulation were scored semi
      quantitatively. RESULTS: In the present study, the level of myringosclerosis was
      significantly lower in lycopene-treated groups compared to the control group
      (p<0.05). In addition, thickness, inflammation, sclerosis, and collagen-IV
      accumulation were significantly lower in the lycopene-treated groups compared to
      the control group (p<0.05). The timing of lycopene administration - i.e. before
      and/or after surgery - did not cause any difference with respect to
      myringosclerosis development. CONCLUSION: Lycopene, a strong antioxidant, may
      represent a good alternative treatment to prevent the development of
      myringosclerosis.

PMID- 25583089
TI  - Catheter ablation of atrial fibrillation in patients with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased incidence
      of atrial fibrillation (AF). This study evaluated the safety and efficacy of
      catheter ablation (CA) in the treatment of AF in patients with RA, which has not
      been previously reported. METHODS: A total of 15 RA patients with AF who
      underwent CA were enrolled. For each RA patient, we selected 4 individuals
      (control group, 60 patients in total) who presented for AF ablation in the
      absence of structural heart or systemic disease and matched the RA patients with
      same gender, age (+/-2 years), type of AF, and procedure date. RESULTS: Patients
      with RA had a significantly higher C-reactive protein level (1.81 +/- 2.35 mg/dl
      vs. 4.14 +/- 2.30 mg/dl, p=0.0320), white blood cell count (5632 +/- 1200 mm(3)
      vs. 6361 +/- 1567 mm(3), p=0.0482), and neutrophil count (3308 +/- 973 mm(3) vs.
      3949 +/- 1461 mm(3), p=0.0441). At 2-year follow-up, atrial tachyarrhythmia (ATa)
      recurrence rate in the RA group (33.3%, 5/15) was similar to that in the control
      group (31.7%, 19/60; p=0.579) after single procedure. In all the five patients
      from the RA group who developed recurrence, ATa relapsed within 90 days following
      index procedure (median recurrence time 18 days vs. 92 days in control group;
      p=0.0373). Multivariate Cox regression analysis showed that hypertension and left
      atrial diameter but not RA, C-reactive protein, white blood cell count, and
      neutrophil count were independent predictors of ATa recurrence. CONCLUSIONS:
      Catheter ablation of AF can be safely performed in patients with RA, with a
      success rate comparable to that of patients without RA. RA patients tend to
      develop early ATa recurrence after AF ablation.

PMID- 25583091
TI  - Impact of crime victimization on initial presentation to an early intervention
      for psychosis service and 18-month outcomes.
AB  - AIM: To investigate the clinical and social correlates of a lifetime history of
      crime victimization among first-episode psychosis patients at entry to an Early
      Intervention Service and following 18 months of specialist care. METHODS: Face-to
      face interviews were conducted with 149 individuals who presented to an Early
      Intervention Service for the first time with psychosis in the London borough of
      Lambeth, UK. A range of demographic and clinical measures were completed
      including self-reported history of victimization along with the type of crime and
      its subjective effect on the patient. Clinical and functional outcomes at 18
      month follow up were ascertained from clinical case notes by a psychiatrist.
      RESULTS: A large proportion of patients (n = 64, 43%) reported a history of crime
      victimization. This was associated with significantly higher levels of depression
      and substance misuse at initial presentation. Being a victim of a crime was not
      significantly associated with poorer clinical or functional outcomes after 18
      months of specialist care. However, non-significant differences were found for
      those who reported crime victimization in terms of their increased use of illegal
      substances or having assaulted someone else during the follow-up period.
      CONCLUSION: Past experience of being a victim of crime appears to be common in
      patients presenting for the first time with psychosis and is associated with
      increased likelihood of comorbidity. Thus, Early Intervention Services should
      consider screening for past victimization and be prepared to deal with comorbid
      problems. The impact of crime victimization on clinical and functional outcomes
      requires investigation over a longer period of time.

PMID- 25583090
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) in heart transplant recipients
      after conversion to everolimus therapy.
AB  - BACKGROUND: Due to the lack of nephrotoxic activity, proliferation signal
      inhibitors (PSI) such as everolimus are recommended for immunosuppression after
      heart transplantation, but the assessment of renal function in patients receiving
      PSI has led to conflicting results. We examined renal integrity and function
      using neutrophil gelatinase-associated lipocalin (NGAL) and conventional markers
      [plasma creatinine, cystatin C, urine albumin, alpha1-microglobulin (alpha1M)] in
      heart transplant patients, who underwent conversion to everolimus due to
      allograft vasculopathy, graft rejection episodes, or renal function
      deterioration, and in patients maintained on calcineurin inhibitors (CNI).
      METHODS: This cross-sectional study included 121 consecutive heart transplant
      recipients: 44 patients received CNI-free immunosuppressive therapy with
      everolimus and 77 patients received CNI. Renal parameters were determined in
      plasma and urine samples using standard enzymatic or immunochemical methods.
      RESULTS: Heart transplant recipients receiving everolimus therapy had
      significantly lower NGAL concentrations in plasma [median (95% CI): 128 (97
      176)ng/mL vs. 252 (224-283)ng/mL, p<0.001] and urine [median (95% CI): 6.4 (4.5
      7.6)ng/g vs. 15.7 (10.2-25.9)ng/g creatinine, p<0.001]. In contrast, no
      significant differences were observed between everolimus- and CNI-treated groups
      with regard to creatinine and cystatin C, as well as urine albumin and alpha1M
      levels. Significant correlations were noted between plasma NGAL and creatinine
      (r=0.42, p<0.001), cystatin C (r=0.44, p<0.001), N-terminal brain natriuretic
      propeptide (r=0.31, p<0.01) and indicators of chronic inflammation [lipoprotein
      associated phospholipase A2 (Lp-PLA2), r=0.31, p<0.01] and soluble CD40 ligand
      (sCD40L, r=0.22, p<0.05), and between urinary NGAL and alpha1M (r=0.21, p<0.05).
      Multiple regression analysis indicated that cystatin C and Lp-PLA2 were the best
      predictors of plasma NGAL. CONCLUSION: The present study documents reduced plasma
      and urinary NGAL levels in the absence of differences in conventional renal
      parameters in patients on CNI-free immunosuppressive therapy with everolimus.
      These results support favorable effects of everolimus on renal integrity in heart
      transplant recipients.

PMID- 25583092
TI  - Skeletal troponin I cross-reactivity in different cardiac troponin I assay
      versions.
AB  - OBJECTIVES: To study the skeletal troponin I (skTnI) cross-reactivity of four
      different commercially available antibodies in four cardiac troponin I (cTnI)
      research assay versions having the same epitope specificity as evidenced by
      peptide mapping. DESIGN AND METHODS: The four research assays all use two solid
      phase antibodies and one detection antibody attached to intrinsically fluorescent
      nanoparticles. Two alternative antibodies were used for one capture antibody and
      two for the detector antibody. The assays were evaluated in terms of analytical
      sensitivity and by determining assay cross-reactivity to skTnI. Additionally,
      regression analysis was performed by measuring a sample panel (n=101) with all of
      the four assay versions. RESULTS: A false-positive cTnI concentration of
      >7000ng/L was measured with one of the assay versions, when serum was spiked with
      500,000ng/L skTnI. The corresponding observed cTnI values for the other three
      assay versions varied from 616ng/L to 727ng/L. Out of the 101 clinical samples
      assayed, five showed spuriously (3- to 148-fold) elevated cTnI values with the
      skTnI interference prone assay setup, but not with the other assay versions.
      According to our investigational skTnI assay, all five samples contained
      measurable amounts of skTnI (range: 5500-702,000ng/L). CONCLUSIONS: Two out of
      four cTnI antibodies tested cross-reacted vastly with skTnI but did not cause any
      notable interference unless paired together. Therefore, skTnI cross-reactivity
      should be carefully assessed when cTnI assay antibodies claimed to be cTnI
      specific are selected.

PMID- 25583093
TI  - Plasma fibroblast growth factor 23 concentration and iron status. Does the
      relationship exist in the elderly population?
AB  - OBJECTIVE: Fibroblast growth factor 23 (FGF23) is a phosphaturic agent involved
      in calcium-phosphate homeostasis. Recent findings show that iron deficiency and
      inflammation regulate FGF23 release and/or biodegradation. Iron deficiency is
      frequently observed in the elderly, therefore the aim of this study was to find
      out if iron deficiency is independent from low grade inflammatory factors
      affecting both forms of FGF23 that are detectable in circulation in a large
      population-based study of elderly subjects. DESIGN AND METHODS: The analysis
      included 3780 elderly (1798 females) PolSenior study participants and assessed
      levels of phosphorus, calcium, iron, ferritin, interleukin 6, C-reactive protein
      (hs-CRP), intact (iFGF23), and c-terminal FGF (cFGF23). The analysis was
      performed for all subjects and terciles of serum iron levels in relation to hs
      CRP were calculated. RESULTS: The highest plasma cFGF23 and iFGF23 concentrations
      were found in subjects with the lowest serum iron levels (p<0.001). The effect of
      low grade inflammation was markedly weaker and affected only iFGF23 levels. The
      adjusted serum levels of hs-CRP, iPTH, phosphorus, and 25-(OH)-D3 analysis
      revealed that plasma iFGF23 and cFGF23 levels were almost unchanged up to a serum
      iron level of 59.3 ng/mL and 57.3 ng/mL respectively and then were nearly
      linearly increasing by 0.285 pg/mL and 3.742 RU/mL for each unit of serum iron
      increase. CONCLUSIONS: Low iron levels are associated with increased levels of
      both cFGF23 and iFGF23, independent of low grade inflammation. A similar analysis
      of cFGF23 and iFGF23 does not suggest enhanced biodegradation of iFGF23 induced
      by iron deficiency.

PMID- 25583094
TI  - ATP-dependent potassium channels and type 2 diabetes mellitus.
AB  - Diabetes mellitus is a public health problem, which affects a millions worldwide.
      Most diabetes cases are classified as type 2 diabetes mellitus, which is highly
      associated with obesity. Type 2 diabetes is considered a multifactorial disorder,
      with both environmental and genetic factors contributing to its development. An
      important issue linked with diabetes development is the failure of the insulin
      releasing mechanism involving abnormal activity of the ATP-dependent potassium
      channel, KATP. This channel is a transmembrane protein encoded by the KCNJ11 and
      ABCC8 genes. Furthermore, polymorphisms in these genes have been linked to type 2
      diabetes because of the role of KATP in insulin release. While several genetic
      variations have been reported to be associated with this disease, the E23K
      polymorphism is most commonly associated with this pathology, as well as to
      obesity. Here, we review the molecular genetics of the potassium channel and
      discusses its most described polymorphisms and their associations with type 2
      diabetes mellitus. 

PMID- 25583095
TI  - Laboratory assessment of cardiometabolic risk in overweight and obese children.
AB  - Childhood obesity has been identified as one of the most important risk factors
      of developing cardiovascular diseases. The global prevalence of overweight and
      obesity among children shows an increasing tendency. Many of overweight or obese
      children will become obese adults with enhanced risk for cardiovascular diseases.
      Childhood obesity is often accompanied by serious consequences such as
      dyslipidemia, hypertension, diabetes, pro-inflammatory state and non-alcoholic
      fatty liver disease. Hypertension, high LDL-cholesterol and triglyceride
      concentrations, insulin resistance, inflammation and disturbances in
      adipocytokines secretion are associated with endothelial dysfunction which
      precedes the development of atherosclerosis. Obese children and adolescents with
      a clinically-proven non-alcoholic fatty liver disease, which is currently
      recognized as the hepatic component of metabolic syndrome, are at more severe
      cardiovascular risk compared with normal-weight. Obesity-related insulin
      resistance is highly prevalent in children and adolescents, and is associated
      with the increased lifetime risk of type 2 diabetes and cardiovascular disease.
      Adipokines contribute to obesity-atherosclerosis relationships yet among several
      recently discovered adipokines only few (adiponectin, resistin, chemerin,
      fibroblast growth factor 21, apelin) have been partly studied in obese pediatric
      population. The aim of this review was to describe the spectrum of cardiovascular
      abnormalities observed in children with overweight and obesity and the role of
      laboratory in the assessment of cardiometabolic risk in order to differentiate
      between healthy obese and those at risk to most effectively prevent progression
      of cardiovascular disease in childhood. 

PMID- 25583096
TI  - Ultrasonic assisted synthesis of gem-dichloroaziridine derivatives using Mg/CCl4
      under neutral conditions.
AB  - A novel and convenient method for synthesis of gem-dichloroaziridine derivatives
      was reported in that was utilized Mg powder with CCl4 for dichlorocarbene
      generation under ultrasonic irradiation. In this clean and efficient reaction
      procedure, the desired products were purely obtained in excellent yields. The
      other advantages of this method are availability of reagents, very short reaction
      times, simplicity of the method, easily work up, neutral reaction medium and high
      purity of products. 

PMID- 25583098
TI  - Chromosome inversions, adaptive cassettes and the evolution of species' ranges.
AB  - A chromosome inversion can spread when it captures locally adapted alleles or
      when it is introduced into a species by hybridization with adapted alleles that
      were previously absent. We present a model that shows how both processes can
      cause a species range to expand. Introgression of an inversion that carries
      novel, locally adapted alleles is a particularly powerful mechanism for range
      expansion. The model supports the earlier proposal that introgression of an
      inversion triggered a large range expansion of a malaria mosquito. These results
      suggest a role for inversions as cassettes of genes that can accelerate
      adaptation by crossing species boundaries, rather than protecting genomes from
      introgression.

PMID- 25583097
TI  - Integration of antenatal syphilis screening in an urban HIV clinic: a feasibility
      study.
AB  - BACKGROUND: Syphilis infection during pregnancy leads to avoidable morbidity and
      mortality and remains a significant problem in sub-Saharan Africa. Despite global
      initiatives to increase the proportion of pregnant women screened, implementation
      has been slow. We sought to investigate the feasibility of adding syphilis
      screening within an integrated antenatal HIV clinic. METHODS: Pregnant women
      attending the HIV antenatal clinic were sequentially enrolled and consenting
      participants answered a questionnaire on sexual behavior and previous
      pregnancies, provided sociodemographic data, and were tested using rapid plasmin
      reagin (RPR). If positive, participants were treated with benzathine penicillin.
      All were given a partner notification slip and were followed up after delivery to
      determine birth outcomes. RESULTS: 584 of 606 (95.7%) women approached and
      consented to test for syphilis. 570 women were enrolled (median age 29 (IQR 25
      32) with a median (IQR) CD4 of 372 (257-569) cells/MUL). Of the 5.1% (29/570)
      with a positive RPR, all were asymptomatic, were successfully contacted, and
      treated with benzathine penicillin without adverse reactions. Overall, 61 (12.1%)
      of the participants had an adverse birth outcome. In the bivariate analysis, only
      age was significantly different between those with and without a positive RPR (RR
      = 1.15, 95% CI 1.065-1.248; p < 0.001). Partners of only 10 (34.5%) participants
      returned for treatment. CONCLUSIONS: Structural interventions such as opt-out
      testing for syphilis within integrated HIV-antenatal care clinics are feasible
      and capitalize on the excellent care programs that have already been established
      for HIV care. Novel approaches are required for partner notification.

PMID- 25583099
TI  - Synthesis and pharmacological evaluation of N-benzyl substituted 4-bromo-2,5
      dimethoxyphenethylamines as 5-HT2A/2C partial agonists.
AB  - N-Benzyl substitution of phenethylamine 5-HT2A receptor agonists has dramatic
      effects on binding affinity, receptor selectivity and agonist activity. In this
      paper we examine how affinity for the 5-HT2A/2C receptors are influenced by N
      benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine derivatives. Special
      attention is given to the 2' and 3'-position of the N-benzyl as such compounds
      are known to be very potent. We found that substitutions in these positions are
      generally well tolerated. The 2'-position was further examined using a range of
      substituents to probe the hydrogen bonding requirements for optimal affinity and
      selectivity, and it was found that small changes in the ligands in this area had
      a profound effect on their affinities. Furthermore, two ligands that lack a 2'
      benzyl substituent were also found to have high affinity contradicting previous
      held notions. Several high-affinity ligands were identified and assayed for
      functional activity at the 5-HT2A and 5-HT2C receptor, and they were generally
      found to be less efficacious agonists than previously reported N-benzyl
      phenethylamines. 

PMID- 25583100
TI  - Anthranilic acid derivatives as nuclear receptor modulators--development of novel
      PPAR selective and dual PPAR/FXR ligands.
AB  - Nuclear receptors, especially the peroxisome proliferator activated receptors
      (PPARs) and the farnesoid X receptor (FXR) fulfill crucial roles in metabolic
      balance. Their activation offers valuable therapeutic potential which has high
      clinical relevance with the fibrates and glitazones as PPAR agonistic drugs. With
      growing knowledge about the various functions of nuclear receptors in many
      disorders, new selective or dual ligands of these pharmaceutical targets are
      however still required. Here we report the class of anthranilic acid derivatives
      as novel selective PPAR or dual FXR/PPAR ligands. We identified distinct
      molecular determinants that govern selectivity for each PPAR subtype or FXR as
      well as the amplitude of activation of the respective receptors. We thereby
      discovered several lead compounds for further optimization and developed a highly
      potent dual PPARalpha/FXR partial agonist that might have a beneficial
      synergistic effect on lipid homeostasis by simultaneous activation of two nuclear
      receptors involved in lipid metabolism. 

PMID- 25583103
TI  - A computational study of the effect of matrix structural order on water sorption
      by Trp-cage miniproteins.
AB  - We present the first simulation study of the impact of protein matrix structure
      on water sorption along with a new computational method to hydrate and dehydrate
      protein systems reversibly. To understand the impact of the underlying structure
      of the protein matrix on the hydration process, we compare three types of protein
      substrates comprised of Trp-cage miniproteins with varying degrees of monomer
      translational and orientational order and monomer denaturation. We show that the
      water sorption isotherms are qualitatively and quantitatively very similar for
      the Trp-cage matrices independently of the underlying degree of disorder, which
      is consistent with the experimental observation that the qualitative features of
      water sorption isotherms are nearly universal for globular proteins. We also show
      that the Trp-cage matrices with varying disorder share similar trends in
      volumetric swelling, solvent accessibility, and protein-water hydrogen bonding
      during the sorption processes, while hydrogen bonding between protein molecules
      depends sensitively on the matrix characteristics (crystal, powder, and thermally
      denatured powder). Volumetric swelling, solvent accessibility, and protein-water
      hydrogen bonds exhibit no hysteresis when plotted as a function of hydration
      level and are thus controlled exclusively by the protein's water content. 

PMID- 25583101
TI  - Patients with atopic dermatitis have attenuated and distinct contact
      hypersensitivity responses to common allergens in skin.
AB  - BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory disease. The
      prevalence of allergic contact dermatitis to allergens (eg, fragrance) is higher
      in patients with AD, despite a trend toward weaker clinical allergic contact
      dermatitis reactions. The role of the AD skin phenotype in modulating allergic
      sensitization to common sensitizers has not been evaluated. OBJECTIVE: We sought
      to investigate whether patients with AD have altered tissue immune responses on
      allergen challenge. METHODS: Gene expression and immunohistochemistry studies
      were performed on biopsy specimens from 10 patients with AD and 14 patients
      without AD patch tested with common contact allergens (nickel, fragrance, and
      rubber). RESULTS: Although 1085 differentially expressed genes (DEGs) were
      commonly modulated in patch-tested skin from patients with AD and patients
      without AD versus control skin, 1185 DEGs were uniquely altered in skin from
      patients without AD, and only 246 DEGs were altered in skin from patients with
      AD. Although many inflammatory products (ie, matrix metalloproteinase 12/matrix
      metalloproteinase 1/S100A9) were upregulated in both groups, higher-magnitude
      changes and upregulation of interferon responses were evident only in the non-AD
      group. Stratification by allergen showed decreased expression of immune, TH1
      subset, and TH2-subset genes in nickel-related AD responses, with increased
      TH17/IL-23 skewing. Rubber/fragrance showed similar trends of lesser magnitude.
      Negative regulators showed higher expression in patients with AD. CONCLUSIONS:
      Through contact sensitization, our study offers new insights into AD. Allergic
      immune reactions were globally attenuated and differentially polarized in
      patients with AD, with significant decreases in levels of TH1 products, some
      increases in levels of TH17 products, and inconsistent upregulation in levels of
      TH2 products. The overall hyporesponsiveness in skin from patients with
      background AD might be explained by baseline immune abnormalities, such as
      increased TH2, TH17, and negative regulator levels compared with those seen in
      non-AD skin.

PMID- 25583102
TI  - Specific epicutaneous immunotherapy prevents sensitization to new allergens in a
      murine model.
AB  - BACKGROUND: Allergy to cow's milk increases the risk of sensitization to other
      foods in young children. OBJECTIVES: We sought to evaluate the effect of early
      epicutaneous immunotherapy (EPIT) on further sensitization to peanut or house
      dust mite (HDM) in a murine model of sensitization to cow's milk. METHODS: BALB/c
      mice orally sensitized to milk were epicutaneously treated with a Viaskin patch
      (DBV Technologies) loaded with milk proteins for 8 weeks. Mice were then
      sensitized to peanut or HDM. After sensitization to peanut, mice were exposed to
      a peanut regimen known to induce eosinophilic esophageal inflammation. After
      sensitization to HDM, mice were challenged with aerosols to HDM, and airway
      hyperresponsiveness was evaluated by using plethysmography. Humoral response was
      also analyzed. The role of regulatory T (Treg) cells was evaluated by adoptively
      transferring Treg cells from milk EPIT-treated mice to naive mice before
      sensitization to peanut. Protection against anaphylaxis was also investigated.
      Methylation of the promoter region of transcription factors was analyzed by using
      PCR assays. RESULTS: In milk-sensitized mice specific EPIT prevented further
      sensitization to peanut or HDM. EPIT significantly modified the humoral response,
      reduced TH2 cytokine levels, decreased eosinophilic esophageal infiltration, and
      suppressed airway hyperresponsiveness. The protective effect was sustained over 2
      months. Moreover, the adoptive transfer of milk EPIT Treg cells completely
      prevented sensitization to peanut and peanut-induced anaphylaxis. Milk EPIT
      enhanced methylation of the GATA-3 promoter region. CONCLUSIONS: Our results
      showed that EPIT influences the natural history of allergy and reduces the risk
      of further sensitization through a Treg cell-dependent mechanism.

PMID- 25583104
TI  - Left ventricular assist device pump thrombosis: understanding mechanisms as a key
      to causality.

PMID- 25583105
TI  - Channels between the ventricles: geometry and geography are both important.

PMID- 25583106
TI  - Association of impaired heart rate recovery with cardiopulmonary complications
      after lung cancer resection surgery.
AB  - OBJECTIVES: Patients who undergo lung resection surgery are at risk for
      postoperative morbidity and mortality. Appropriate selection of the surgical
      candidate is crucial in the treatment of lung cancer. Heart rate recovery is a
      measure of physical fitness. We aimed to investigate the association of impaired
      heart rate recovery with cardiopulmonary complications after lung resection
      surgery for treatment of lung cancer. METHODS: Data from consecutive patients
      who, between 2009 and 2013, underwent heart rate recovery evaluation after 6
      minute walk tests before lung resection surgery were retrospectively reviewed.
      Impaired heart rate recovery was defined as a 12-beat or less decrease in peak
      heart rate at 1 minute after the 6-minute walk test. Postoperative
      cardiopulmonary complications were as defined by the Society of Thoracic Surgeons
      General Thoracic Surgery Database. Logistic regression was performed, including
      previously known risk factors for postoperative complications after lung
      resection surgery. RESULTS: A total of 96 patients had heart rate recovery
      evaluated within 6 months of lung resection surgery for treatment of lung cancer.
      Thirty-one patients had impaired heart rate recovery, 17 of whom (55%) had
      cardiopulmonary complications. A total of 65 patients had normal heart rate
      recovery, 17 of whom (26%) had cardiopulmonary complications. In multivariable
      logistic regression analysis, impaired heart rate recovery was significantly
      associated with postoperative cardiopulmonary complications (odds ratio, 4.97;
      confidence interval, 1.79-13.8; P = .002). No patient died within 30 days after
      surgery. CONCLUSIONS: Impaired heart rate recovery after the 6-minute walk test
      is associated with postoperative cardiopulmonary complications in patients who
      underwent lung resection surgery for treatment of lung cancer.

PMID- 25583107
TI  - Outcomes of intraoperative extracorporeal membrane oxygenation versus
      cardiopulmonary bypass for lung transplantation.
AB  - OBJECTIVE: The study objective was to compare the outcomes of intraoperative
      extracorporeal membrane oxygenation versus cardiopulmonary bypass support in lung
      transplantation. METHODS: We performed a retrospective cohort study from a
      prospective database of adult lung transplantations performed at the University
      of Toronto from 2007 to 2013. Among 673 lung transplantations performed in the
      study period, 267 (39.7%) required cardiopulmonary support. There were 39 cases
      of extracorporeal membrane oxygenation (2012-2013) and 228 cases of
      cardiopulmonary bypass (2007-2013). Patients who were bridged with extracorporeal
      life support, underwent a concomitant cardiac procedure, received a combined
      liver or heart transplant, were colonized with Burkholderia cenocepacia, or
      required emergency cannulation for cardiopulmonary support were excluded.
      Finally, 33 extracorporeal membrane oxygenation cases were matched with 66 cases
      of cardiopulmonary bypass according to age (+/-10 years), lung transplantation
      indication, and procedure type (bilateral vs single lung transplantation).
      RESULTS: Recipient factors such as body mass index and gender were not different
      between extracorporeal membrane oxygenation and cardiopulmonary bypass groups.
      Furthermore, donor variables were similar, including age, body mass index, last
      PaO2/FiO2 ratio, smoking history, positive airway cultures, and donor type (brain
      death and donation after cardiac death). Early outcomes, such as mechanical
      ventilation requirement, length of intensive care unit stay, and length of
      hospital stay, significantly favored extracorporeal membrane oxygenation (median
      3 vs 7.5 days, P = .005; 5 vs 9.5 days, P = .026; 19 vs 27 days, P = .029,
      respectively). Perioperative blood product transfusion requirement was lower in
      the extracorporeal membrane oxygenation group. The 90-day mortality for the
      extracorporeal membrane oxygenation group was 6% versus 15% for cardiopulmonary
      bypass (P = .32). CONCLUSIONS: Extracorporeal membrane oxygenation may be
      considered as the first choice of intraoperative cardiorespiratory support for
      lung transplantation.

PMID- 25583109
TI  - To bypass or stent? The changing rules of an advancing game.

PMID- 25583108
TI  - Right ventricular failure secondary to chronic overload in congenital heart
      diseases: benefits of cell therapy using human embryonic stem cell-derived
      cardiac progenitors.
AB  - OBJECTIVE: Despite the increasing incidence of right ventricular (RV) failure in
      adult patients with congenital heart disease, current therapeutic options are
      still limited. By contrast to left-heart diseases, cell-based myocardial
      regeneration applied to the right ventricle is poorly studied, even though it may
      be a therapeutic solution. As human embryonic stem cell-derived cardiac
      progenitors seem to be good candidates owing to their proliferation capacity, our
      aim was to assess, in a large animal model of overloaded RV dysfunction, the
      feasibility and effects of such a cell therapy. METHODS: Human MesP1(+)/SSEA-1(+)
      cardiogenic mesodermal cells were administered using multiple intramyocardial
      injections 4 months after a surgical procedure mimicking the repaired tetralogy
      of Fallot, and their effects were observed 3 months later on hemodynamic,
      rhythmic, and histologic parameters. RESULTS: All pigs (sham n = 6, treated n =
      6) survived without complication, and cell therapy was clinically well tolerated.
      Although functional, contractility, and energetics parameters evolved similarly
      in both groups, benefits regarding arrhythmic susceptibility were observed in the
      treated group, associated with a significant decrease of peri-myocyte fibrosis
      (5.71% +/- 2.49% vs 12.12% +/- 1.85%; P < .01) without interstitial fibrosis
      change (5.18% +/- 0.81% vs 5.49% +/- 1.01%). Such a decrease could be related to
      paracrine effects, as no human cells could be detected within the myocardium.
      CONCLUSIONS: Cell therapy using intramyocardial injections of human MesP1(+)/SSEA
      1(+) cardiogenic mesodermal cells seems to have benefits regarding overloaded RV
      tissue remodeling and arrhythmic susceptibility, but this mode of administration
      is not sufficient to obtain a significant improvement in RV function.

PMID- 25583110
TI  - Might erythropoietin save the spinal cord in aortic interventions?

PMID- 25583111
TI  - The data and use of bilateral internal thoracic artery grafting: a paradox
      indeed.

PMID- 25583112
TI  - Devaki syndrome: a culture-bound psychological reaction in Indian Hindu women in
      response to repeated pregnancy loss?
AB  - Depression and anxiety are observed in pregnant women with previous foetal loss
      due to spontaneous abortions. Culture has important influence on the expression
      of psychopathology. We report two Hindu women during second trimester of
      pregnancy with symptoms of depression and anxiety along with identification with
      a mythological figure - Devaki, with extreme preoccupations with child Krishna
      and expecting a male child, which precipitated after a series of unfortunate
      foetal losses. 

PMID- 25583113
TI  - MicroRNA-1 aggravates cardiac oxidative stress by post-transcriptional
      modification of the antioxidant network.
AB  - Oxidative stress plays an important role in cardiovascular diseases. Studies have
      shown that miR-1 plays an important role in the regulation of cardiomyocyte
      apoptosis, which can be the result of oxidative stress. This study was designed
      to determine whether increased miR-1 levels lead to alterations in the expression
      of proteins related to oxidative stress, which could contribute to heart
      dysfunction. We compared cardiac function in wild-type (WT) and miR-1 transgene
      (miR-1/Tg) C57BL/6 mice (n >= 10/group). Echocardiography showed that stroke
      volume (SV), ejection fraction (EF), and fractional shortening (FS) were
      significantly decreased in miR-1/Tg mice. Concomitantly, the level of reactive
      oxygen species (ROS) was elevated in the cardiomyocytes from the miR-1/Tg mice,
      and activities of lactate dehydrogenase (LDH) and creatinine kinase (CK) in
      plasma were also increased in the miR-1/Tg mice. All of these changes could be
      reversed by LNA-anti-miR-1. In the cardiomyocytes of neonatal Wistar rats,
      overexpression of miR-1 exhibits higher ROS levels and lower resistance to H2O2
      induced oxidative stress. We demonstrated that SOD1, Gclc, and G6PD are novel
      targets of miR-1 for post-transcriptional repression. MicroRNA-1 post
      transcriptionally represses the expression of SOD1, Gclc, and G6PD, which is
      likely to contribute to the increased ROS level and the susceptibility to
      oxidative stress of the hearts of miR-1 transgenic mice. 

PMID- 25583114
TI  - Astrocytes and mitochondria from adrenoleukodystrophy protein (ABCD1)-deficient
      mice reveal that the adrenoleukodystrophy-associated very long-chain fatty acids
      target several cellular energy-dependent functions.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disorder
      resulting from defective ABCD1 transport protein. ABCD1 mediates peroxisomal
      uptake of free very-long-chain fatty acids (VLCFA) as well as their CoA-esters.
      Consequently, VLCFA accumulate in patients' plasma and tissues, which is
      considered as pathogenic X-ALD triggering factor. Clinical symptoms are mostly
      manifested in neural tissues and adrenal gland. Here, we investigate astrocytes
      from wild-type control and a genetic X-ALD mouse model (Abcd1-knockout), exposed
      to supraphysiological VLCFA (C22:0, C24:0 and C26:0) concentrations. They exhibit
      multiple impairments of energy metabolism. Furthermore, brain mitochondria from
      Abcd1(-/-) mice and wild-type control respond similarly to VLCFA with increased
      ROS generation, impaired oxidative ATP synthesis and diminished Ca(2+) uptake
      capacity, suggesting that a defective ABCD1 exerts no adaptive pressure on
      mitochondria. In contrast, astrocytes from Abcd1(-/-) mice respond more
      sensitively to VLCFA than wild-type control astrocytes. Moreover, long-term
      application of VLCFA induces high ROS generation, and strong in situ
      depolarization of mitochondria, and, in Abcd1(-/-) astrocytes, severely
      diminishes the capability to revert oxidized pyridine nucleotides to NAD(P)H. In
      addition, observed differences in responses of mitochondria and astrocytes to the
      hydrocarbon chain length of VLCFA suggest that detrimental VLCFA activities in
      astrocytes involve defective cellular functions other than mitochondria. In
      summary, we clearly demonstrate that VLCFA increase the vulnerability of Abcd1(-/
      ) astrocytes. 

PMID- 25583115
TI  - Disturbance of energy and redox homeostasis and reduction of Na+,K+-ATPase
      activity provoked by in vivo intracerebral administration of ethylmalonic acid to
      young rats.
AB  - Ethylmalonic acid (EMA) accumulation occurs in various metabolic diseases with
      neurological manifestation, including short acyl-CoA dehydrogenase deficiency
      (SCADD) and ethylmalonic encephalopathy (EE). Since pathophysiological mechanisms
      responsible for brain damage in these disorders are still poorly understood, we
      investigated the ex vivo effects of acute intrastriatal administration of EMA on
      important parameters of energy and redox homeostasis in striatum from young rats.
      We evaluated CO(2) production from glucose, glucose utilization and lactate
      production, as well as the activities of the citric acid cycle (CAC) enzymes, the
      electron transfer chain (ETC) complexes II-IV (oxidative phosphorylation, OXPHOS)
      and synaptic Na(+),K(+)-ATPase. We also tested the effect of EMA on
      malondialdehyde (MDA) levels (marker of lipid oxidation) and reduced glutathione
      (GSH) levels. EMA significantly reduced CO(2) production, increased glucose
      utilization and lactate production, and reduced the activities of citrate
      synthase and of complexes II and II-III of the ETC, suggesting an impairment of
      CAC and OXPHOS. EMA injection also reduced Na(+),K(+)-ATPase activity and GSH
      concentrations, whereas MDA levels were increased. Furthermore, EMA-induced
      diminution of Na(+),K(+)-ATPase activity and reduction of GSH levels were
      prevented, respectively, by the antioxidants melatonin and N-acetylcysteine,
      indicating that reactive species were involved in these effects. Considering the
      importance of CAC and ETC for energy production and Na(+),K(+)-ATPase for the
      maintenance of the cell membrane potential, the present data indicate that EMA
      compromises mitochondrial homeostasis and neurotransmission in striatum. We
      presume that these pathomechanisms may be involved to a certain extent in the
      neurological damage found in patients affected by SCADD and EE.

PMID- 25583116
TI  - Resveratrol and inflammation: Challenges in translating pre-clinical findings to
      improved patient outcomes.
AB  - Throughout the Western world obesity prevalence is steadily increasing, and
      associated metabolic co-morbidities are projected to rise during the years to
      come. As weight loss and weight maintenance remains a major problem, new
      strategies to protect against obesity-related morbidity are needed. There is a
      clear association between obesity, low-grade inflammation and obesity-associated
      diseases, thus, the development of new anti-inflammatory substances is urgently
      needed as these may ultimately pave the way for novel treatments of obesity and
      lifestyle-related diseases. A candidate molecule is the polyphenolic compound
      resveratrol, and in the present review, we provide an overview of the field, and
      discuss the future scientific perspectives. This article is part of a Special
      Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to
      improved patient outcomes. 

PMID- 25583117
TI  - Health economics and health policy: experiences from New Zealand.
AB  - Health economics has had a significant impact on the New Zealand health system
      over the past 30 years. In this paper, I set out a framework for thinking about
      health economics, give some historical background to New Zealand and the New
      Zealand health system, and discuss examples of how health economics has
      influenced thinking about the organisation of the health sector and priority
      setting. I conclude the paper with overall observations about the role of health
      economics in health policy in New Zealand, also identifying where health
      economics has not made the contribution it could and where further influence
      might be beneficial. 

PMID- 25583118
TI  - PASPA: a web server for mRNA poly(A) site predictions in plants and algae.
AB  - MOTIVATION: Polyadenylation is an essential process during eukaryotic gene
      expression. Prediction of poly(A) sites helps to define the 3' end of genes,
      which is important for gene annotation and elucidating gene regulation
      mechanisms. However, due to limited knowledge of poly(A) signals, it is still
      challenging to predict poly(A) sites in plants and algae. PASPA is a web server
      for P: oly( A: ) S: ite prediction in P: lants and A: lgae, which integrates many
      in-house tools as add-ons to facilitate poly(A) site prediction, visualization
      and mining. This server can predict poly(A) sites for ten species, including
      seven previously poly(A) signal non-characterized species, with sensitivity and
      specificity in a range between 0.80 and 0.95.

PMID- 25583119
TI  - An integrative approach to predicting the functional effects of non-coding and
      coding sequence variation.
AB  - MOTIVATION: Technological advances have enabled the identification of an
      increasingly large spectrum of single nucleotide variants within the human
      genome, many of which may be associated with monogenic disease or complex traits.
      Here, we propose an integrative approach, named FATHMM-MKL, to predict the
      functional consequences of both coding and non-coding sequence variants. Our
      method utilizes various genomic annotations, which have recently become
      available, and learns to weight the significance of each component annotation
      source. RESULTS: We show that our method outperforms current state-of-the-art
      algorithms, CADD and GWAVA, when predicting the functional consequences of non
      coding variants. In addition, FATHMM-MKL is comparable to the best of these
      algorithms when predicting the impact of coding variants. The method includes a
      confidence measure to rank order predictions.

PMID- 25583120
TI  - Repulsive parallel MCMC algorithm for discovering diverse motifs from large
      sequence sets.
AB  - MOTIVATION: The motif discovery problem consists of finding recurring patterns of
      short strings in a set of nucleotide sequences. This classical problem is
      receiving renewed attention as most early motif discovery methods lack the
      ability to handle large data of recent genome-wide ChIP studies. New ChIP
      tailored methods focus on reducing computation time and pay little regard to the
      accuracy of motif detection. Unlike such methods, our method focuses on
      increasing the detection accuracy while maintaining the computation efficiency at
      an acceptable level. The major advantage of our method is that it can mine
      diverse multiple motifs undetectable by current methods. RESULTS: The repulsive
      parallel Markov chain Monte Carlo (RPMCMC) algorithm that we propose is a
      parallel version of the widely used Gibbs motif sampler. RPMCMC is run on
      parallel interacting motif samplers. A repulsive force is generated when
      different motifs produced by different samplers near each other. Thus, different
      samplers explore different motifs. In this way, we can detect much more diverse
      motifs than conventional methods can. Through application to 228 transcription
      factor ChIP-seq datasets of the ENCODE project, we show that the RPMCMC algorithm
      can find many reliable cofactor interacting motifs that existing methods are
      unable to discover.

PMID- 25583122
TI  - Non-hazardous Baeyer-Villiger oxidation of levulinic acid derivatives:
      alternative renewable access to 3-hydroxypropionates.
AB  - Baeyer-Villiger monooxygenases catalyze the energetically challenging oxidation
      of levulinates (4-oxopentanoates) to 3-hydroxypropionic acid (3-HPA) derivates
      under ambient conditions, replacing propellant-grade H2O2 with aerial oxygen as
      the oxidant. This reaction enables a new pathway to a platform for chemical 3
      HPA, an important intermediate in the non-petrol based production of a variety of
      bulk chemicals (acrylates, malonates, 1,3-propanediol). 

PMID- 25583121
TI  - CellCODE: a robust latent variable approach to differential expression analysis
      for heterogeneous cell populations.
AB  - MOTIVATION: Identifying alterations in gene expression associated with different
      clinical states is important for the study of human biology. However, clinical
      samples used in gene expression studies are often derived from heterogeneous
      mixtures with variable cell-type composition, complicating statistical analysis.
      Considerable effort has been devoted to modeling sample heterogeneity, and
      presently, there are many methods that can estimate cell proportions or pure cell
      type expression from mixture data. However, there is no method that
      comprehensively addresses mixture analysis in the context of differential
      expression without relying on additional proportion information, which can be
      inaccurate and is frequently unavailable. RESULTS: In this study, we consider a
      clinically relevant situation where neither accurate proportion estimates nor
      pure cell expression is of direct interest, but where we are rather interested in
      detecting and interpreting relevant differential expression in mixture samples.
      We develop a method, Cell-type COmputational Differential Estimation (CellCODE),
      that addresses the specific statistical question directly, without requiring a
      physical model for mixture components. Our approach is based on latent variable
      analysis and is computationally transparent; it requires no additional
      experimental data, yet outperforms existing methods that use independent
      proportion measurements. CellCODE has few parameters that are robust and easy to
      interpret. The method can be used to track changes in proportion, improve power
      to detect differential expression and assign the differentially expressed genes
      to the correct cell type.

PMID- 25583123
TI  - Treatment of uncomplicated malaria with artesunate plus sulfadoxine-pyrimethamine
      is failing in Somalia: evidence from therapeutic efficacy studies and Pfdhfr and
      Pfdhps mutant alleles.
AB  - OBJECTIVE: Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been Somalia's
      national treatment policy since 2006. Routine monitoring of first-line malaria
      treatment is needed to ensure appropriate national malaria treatment policy and
      early detection of drug resistance. For this purpose, we conducted therapeutic
      efficacy studies of AS + SP for the treatment of uncomplicated malaria in Somalia
      in 2011. METHODS: Studies were conducted in three sentinel sites. Eligible
      patients were evaluated for clinical and parasitological outcomes according to
      the WHO standard protocol. Molecular surveillance was conducted on resistance
      conferring mutations in the P.falciparum dihydrofolate reductase (dfhr) and
      dihydropteroate synthase (dhps) genes. RESULTS: The proportion of PCR-corrected
      treatment failures was high in Jamame (22%, 95% CI: 13.7-32.8%) and low (<5%) in
      Janale and Jowhar. All patients cleared parasites by day 3. Molecular markers
      associated with SP resistance were detected in all three sites. Treatment failure
      was associated with the presence of the double mutant dhps A437G/K540E (OR =
      22.4, 95% CI: 5.1-98.1), quadruple mutant dhfr N51I/S108N+dhps A437G/K540E (OR =
      5.5, 95% CI: 2.3-13.6), quintuple mutant dhfr N51I/C59R/S108N+dhps A437G/K540E
      (OR = 3.5, 95% CI: 1.4-8.8) and younger age (OR=0.86, 95% CI: 0.76-0.96).
      CONCLUSIONS: The high treatment failure rate observed in Jamame, together with
      the presence of molecular mutations associated with SP resistance, indicates P.
      falciparum resistance to SP. In Jowhar, high treatment failure rates were absent
      despite the presence of molecular mutations; signs of resistance in vivo may have
      been masked by the stronger immunity of the older study population. The study
      underscores the need to update Somalia's national malaria treatment policy.

PMID- 25583124
TI  - Barriers to cervical cancer screening among ethnic minority women: a qualitative
      study.
AB  - BACKGROUND: Ethnic minority women are less likely to attend cervical screening.
      AIM: To explore self-perceived barriers to cervical screening attendance among
      ethnic minority women compared to white British women. DESIGN: Qualitative
      interview study. SETTING: Community groups in ethnically diverse London boroughs.
      METHODS: Interviews were carried out with 43 women from a range of ethnic
      minority backgrounds (Indian, Pakistani, Bangladeshi, Caribbean, African, Black
      British, Black other, White other) and 11 White British women. Interviews were
      recorded, transcribed verbatim and analysed using Framework analysis. RESULTS:
      Fifteen women had delayed screening/had never been screened. Ethnic minority
      women felt that there was a lack of awareness about cervical cancer in their
      community, and several did not recognise the terms 'cervical screening' or 'smear
      test'. Barriers to cervical screening raised by all women were emotional (fear,
      embarrassment, shame), practical (lack of time) and cognitive (low perceived
      risk, absence of symptoms). Emotional barriers seemed to be more prominent among
      Asian women. Low perceived risk of cervical cancer was influenced by beliefs
      about having sex outside of marriage and some women felt a diagnosis of cervical
      cancer might be considered shameful. Negative experiences were well remembered by
      all women and could be a barrier to repeat attendance. CONCLUSIONS: Emotional
      barriers (fear, embarrassment and anticipated shame) and low perceived risk might
      contribute to explaining lower cervical screening coverage for some ethnic
      groups. Interventions to improve knowledge and understanding of cervical cancer
      are needed in ethnic minority communities, and investment in training for health
      professionals may improve experiences and encourage repeat attendance for all
      women.

PMID- 25583126
TI  - Bordetella parapertussis outbreak in Bisham, Pakistan in 2009-2010: fallout of
      the 9/11 syndrome.
AB  - Pertussis or whooping cough is a highly contagious community disease mainly
      caused by Bordetella pertussis and B. parapertussis. We report a minor outbreak
      of whooping cough (2009-2010) in symptomatic subjects from Bisham, near Swat,
      Khyber Pukhtoonkhawa province, Pakistan. Interestingly, our results show that all
      the culture-positive isolates (n = 21) collected from children (average age 3.46
      years), were identified as B. parapertussis after routine identification tests
      and PCR IS481, IS1001 and IS1002. Furthermore, in the affected patients, none had
      received immunization with diphtheria-pertussis-tetanus (DTPw) vaccine.
      Therefore, the possibility of the re-emergence of the disease due to limitation
      of basic health services as a result of the political unrest due to the 9/11
      situation is also examined. Moreover, we discuss the importance of vaccinating
      both adults and children with DTPwPaw vaccine containing both organisms for
      better protection. 

PMID- 25583125
TI  - Adjusting tidal volume to stress index in an open lung condition optimizes
      ventilation and prevents overdistension in an experimental model of lung injury
      and reduced chest wall compliance.
AB  - INTRODUCTION: The stress index (SI), a parameter derived from the shape of the
      pressure-time curve, can identify injurious mechanical ventilation. We tested the
      hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung
      condition avoids hypoventilation while preventing overdistension in an
      experimental model of combined lung injury and low chest-wall compliance (Ccw).
      METHODS: Lung injury was induced by repeated lung lavages using warm saline
      solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in
      22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals
      were recruited and submitted to a positive end-expiratory pressure (PEEP)
      titration trial to find the PEEP level resulting in maximum compliance. During a
      subsequent four hours of mechanical ventilation, VT was adjusted to keep a
      plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between
      0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a
      'normal' PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases
      haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In
      addition Computed Tomography (CT) data were acquired at end expiration and end
      inspiration in six animals. RESULTS: PaCO2 was significantly higher in the Pplat
      group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34,
      P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg(-1), P
      = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group
      and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory
      transpulmonary pressure (PTP) (17 versus 18 cmH2O, P = 0.42) were similar in the
      Pplat- and SI-groups respectively, without differences in overinflated lung areas
      at end- inspiration in both groups. Cytokines and histopathology showed no
      differences. CONCLUSIONS: Setting tidal volume to a non-injurious stress index in
      an open lung condition improves alveolar ventilation and prevents overdistension
      without increasing lung injury. This is in comparison with limited Pplat
      protective ventilation in a model of lung injury with low chest-wall compliance.

PMID- 25583127
TI  - Divergent approach to building a latrunculin family derived hybrid macrocyclic
      toolbox.
AB  - A divergent approach to obtain a latrunculin family based hybrid macrocyclic
      toolbox is developed. A practical, stereoselective synthesis of a common
      substructure present in latrunculin A and latrunculol A was achieved. This was
      further utilized in the macrocyclic diversity synthesis. The amino acid moiety
      embedded in the 15-membered macrocyclic ring allows for the exploration of
      various chiral side chains as one of the diversity sites. 

PMID- 25583128
TI  - Pathological rib fracture and soft tissue mass simulating malignancy-
      Cryptococcus, an unsuspected culprit.
AB  - A patient presented with a pathological rib fraction and associated soft tissue
      mass thought initially to represent a soft tissue neoplasm. However, further
      consideration of infectious etiologies led to the identification of cryptococcal
      osteomyelitis. Cryptococcus infection should be considered in the differential of
      pathological fractures with soft tissue involvement. 

PMID- 25583129
TI  - Evaluation of novel second-generation RSV and influenza rapid tests at the point
      of care.
AB  - Acute respiratory infections represent common pediatric emergencies. Infection
      control warrants immediate and accurate diagnoses. In the past, first-generation
      respiratory syncytial virus (RSV) rapid tests (strip tests) have shown suboptimal
      sensitivities. In 2013, the Food and Drug Administration licensed a second
      generation RSV rapid test providing user-independent readouts (SOFIATM-RSV) using
      automated fluorescence assay technology known to yield superior results with
      influenza rapid testing. We are reporting the first point-of-care evaluation of
      the SOFIATM-RSV rapid test. In the Charite Influenza-Like Disease Cohort, 686
      nasopharyngeal samples were tested in parallel with SOFIATM-RSV and SOFIATM
      Influenza A+B. Compared to real-time PCR, SOFIATM-RSV sensitivities/specificities
      were 78.6%/93.9%, respectively (SOFIATM-Influenza A: 80.6%/99.3%). Performance
      was greatest in patients below 2 years of age with a test sensitivity of 81.8%.
      RSV sensitivities were highest (85%) in the first 2 days of illness and with
      nasopharyngeal compared to nasal swabs (P=0.055, McNemar's test). Second
      generation RSV and influenza rapid testing provides highly accurate results
      facilitating timely patient cohortation and management.

PMID- 25583130
TI  - Ceftaroline: clinical and microbiology experience with focus on methicillin
      resistant Staphylococcus aureus after regulatory approval in the USA.
AB  - Ceftaroline fosamil was approved in 2010 by the United States Food and Drug
      Administration (USA-FDA) for the treatment of patients with acute bacterial skin
      and skin structure infections (ABSSSIs) and community-acquired bacterial
      pneumonia (CABP). After approval, several studies and case reports have described
      the postmarketing clinical experience with ceftaroline in ABSSSIs and CABP and in
      patients with invasive methicillin-resistant Staphylococcus aureus (MRSA)
      infections, many of whom had failed prior antibiotics. Successful clinical
      outcomes observed among the majority of these patients were supported by
      preapproval and postapproval in vitro surveillance of ceftaroline activity using
      breakpoint criteria that have been harmonized between the USA-FDA and CLSI. MIC90
      values/percentage of strains susceptible to ceftaroline has remained stable over
      the period 2009-2012. Taken together, these postapproval studies support the use
      of ceftaroline for ABSSSI as well as CABP. Importantly, these data also suggest
      that ceftaroline can be effective in patients with serious invasive MRSA
      infections who have failed other therapies. 

PMID- 25583131
TI  - A structure-activity relationship study of the toxicity of ionic liquids using an
      adapted Ferreira-Kiralj hydrophobicity parameter.
AB  - The Ferreira-Kiralj hydrophobicity parameter Wc is a number fraction of
      hydrophobic carbon atoms and can be regarded as a constitutional descriptor since
      its calculation depends only on the number of polar and nonpolar carbons in a
      compound. Hydrophobicity is important to the toxicity of ionic liquids (ILs),
      which are salts by nature. Herein, a descriptor for this property was calculated
      using a simple adaptation of the type of polar carbon atoms included (WcAdap) to
      explore the possibility of its use in quantitative structure-activity
      relationship (QSAR) studies of ILs. The resulting model was tested using a
      database of ILs with toxicity against the Leukemia rat cell line IPC-81. Two
      other models were constructed using Crippen log P and Mannhold log P descriptors,
      which are both available in the free program PaDEL. The use of WcAdap led to a
      better and more indicative model. Thus, WcAdap may be a suitable molecular
      descriptor for the hydrophobicity of ILs in QSAR studies. 

PMID- 25583132
TI  - Meat subtypes and their association with colorectal cancer: Systematic review and
      meta-analysis.
AB  - Associations between specific red meat subtypes and risk of colorectal cancer
      (CRC) have been investigated in a number of epidemiological studies. However, no
      publication to date has summarised the overall epidemiological evidence. We
      conducted a systematic review and meta-analysis of prospective studies (cohort,
      nested case-control or case-cohort studies), which reported relative risk (RR)
      estimates and 95% confidence intervals (CI) for the association between intake of
      meat subtypes with colorectal, colon or rectal cancer or colorectal adenoma risk.
      PubMed and ISI Web of Science were searched up until August 1, 2014. Nineteen
      studies examined meat subtypes (5 beef, 5 pork, 2 lamb, 1 veal and 19 poultry)
      and associations with colorectal, colon or rectal cancer risk and 4 studies
      examined associations with adenoma risk (1 beef and 4 poultry). Comparing highest
      versus lowest intake, beef consumption was associated with an increased risk of
      CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07
      to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI =
      0.78 to 1.16). Higher consumption of lamb was also associated with increased risk
      of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork
      (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was
      observed. No association was observed for poultry consumption and risk of
      colorectal adenomas or cancer. This meta-analysis suggests that red meat subtypes
      differ in their association with CRC and its sub sites. Further analysis of data
      from prospective cohort studies is warranted, especially regarding the role of
      pork.

PMID- 25583133
TI  - A borane laser.
AB  - Emission from electronically excited species forms the basis for an important
      class of light sources-lasers. So far, commercially available solution-processed
      blue-emitting laser materials are based on organic compounds or semiconductor
      nanocrystals that have significant limitations: either low solubility, low
      chemical- and/or photo-stability and/or uncompetitive prices. Here we report a
      novel and competitive alternative to these existing laser materials that is based
      on boron hydrides, inorganic cluster compounds with a rich and diverse chemistry.
      We demonstrate that solutions of the borane anti-B18H22 show, under pulsed
      excitation, blue laser emission at 406 nm with an efficiency (ratio of
      output/input energies) of 9.5%, and a photostability superior to many of the
      commercially available state-of-the-art blue laser dyes. This demonstration opens
      the doors for the development of a whole new class of laser materials based on a
      previously untapped resource for laser technology-the boranes.

PMID- 25583134
TI  - Investigation of protective role of curcumin against paclitaxel-induced inner ear
      damage in rats.
AB  - OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate the potential
      protective effect of curcumin on paclitaxel-induced ototoxicity in rats by means
      of immunohistochemical and histopathological analysis and distortion product
      otoacoustic emissions (DPOAEs). STUDY DESIGN: Animal study. METHODS: Forty
      Sprague-Dawley rats were randomized into five groups. Group 1 was administered no
      paclitaxel and curcumin during the study. Groups 2, 3, 4 and 5 were administered
      5 mg/kg paclitaxel; 200 mg/kg curcumin; 5 mg/kg paclitaxel, followed by 200 mg/kg
      curcumin; 200 mg/kg curcumin and a day later 5 mg/kg paclitaxel followed
      intraperitoneally by 200 mg/kg curcumin once a week for 4 consecutive weeks,
      respectively. After the final DPOAEs test, the animals were sacrificed and their
      cochlea were prepared for hematoxylin and eosin and caspase-3 staining. RESULTS:
      The DPOAEs thresholds and histopathological and immunohistochemical findings were
      substantially correlated in all groups. The histopathologic findings in the
      cochlea of the paclitaxel-treated animals showed not only changes in the organ of
      Corti, but also damage to the stria vascularis and spiral limbus, including
      nuclear degeneration, cytoplasmic vacuolization, and atrophy of intermediate
      cells. Additionally, cochlear changes in group 2, such as intense apoptosis, were
      confirmed by caspase-3 immunohistochemical staining. In group 4, coreceiving
      curcumin could not sufficiently prevent paclitaxel-induced ototoxicity, and the
      results in group 5 were similar to the control group. CONCLUSIONS: In our study,
      we have concluded that pre- and coreceiving curcumin can significantly protect
      the cochlear morphology and functions on paclitaxel-induced ototoxicity in rats.
      Curcumin might be considered as a potential natural product that, used as a
      dietary supplement, could be easily given to patients undergoing paclitaxel
      chemotherapy. LEVEL OF EVIDENCE: NA

PMID- 25583135
TI  - Effect of carbonic anhydrase on silicate weathering and carbonate formation at
      present day CO2 concentrations compared to primordial values.
AB  - It is widely recognized that carbonic anhydrase (CA) participates in silicate
      weathering and carbonate formation. Nevertheless, it is still not known if the
      magnitude of the effect produced by CA on surface rock evolution changes or not.
      In this work, CA gene expression from Bacillus mucilaginosus and the effects of
      recombination protein on wollastonite dissolution and carbonate formation under
      different conditions are explored. Real-time fluorescent quantitative PCR was
      used to explore the correlation between CA gene expression and sufficiency or
      deficiency in calcium and CO2 concentration. The results show that the expression
      of CA genes is negatively correlated with both CO2 concentration and ease of
      obtaining soluble calcium. A pure form of the protein of interest (CA) is
      obtained by cloning, heterologous expression, and purification. The results from
      tests of the recombination protein on wollastonite dissolution and carbonate
      formation at different levels of CO2 concentration show that the magnitudes of
      the effects of CA and CO2 concentration are negatively correlated. These results
      suggest that the effects of microbial CA in relation to silicate weathering and
      carbonate formation may have increased importance at the modern atmospheric CO2
      concentration compared to 3 billion years ago.

PMID- 25583136
TI  - Primary radiotherapy or postoperative radiotherapy in patients with head and neck
      cancer: Comparative analysis of inflammation-based prognostic scoring systems.
AB  - INTRODUCTION: Inflammation-based scoring systems have potential value in
      evaluating the prognosis of cancer patients; however, detailed comparative
      analyses in well-characterized head and neck cancer patient collectives are
      missing. METHODS: We analyzed overall survival (OS) in locally advanced head and
      neck cancer patients who were treated with curative intent by primary
      radiotherapy (RT) alone, by RT in combination with cetuximab (RIT) or with
      cisplatin (RCHT), and by primary surgery followed by postoperative radiotherapy
      (PORT). The primary RT collective (N = 170) was analyzed separately from the
      surgery plus RT group (N = 148). OS was estimated using the Kaplan-Meyer method.
      Cox proportional-hazard regression models were applied to compare the risk of
      death among patients stratified according to risk factors and the inflammation
      based Glasgow Prognostic Score (GPS), the modified GPS (mGPS), the neutrophil
      lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the prognostic
      index (PI). RESULTS: A prognostic relevance of the scoring systems for OS was
      observed in the primarily irradiated, but not in the PORT collective. OS was
      35.5, 18.8, and 15.4 months, respectively, according to GPS 0, 1, and 2. OS
      according to mGPS 0-2 was identical. The PLR scoring system was not of prognostic
      relevance, while OS was 27.3 months in the NLR 0 group and 17.3 months in the NLR
      1 group. OS was 35.5 months in PI 0, 16.1 months in PI 1, and 22.6 months in PI
      2. CONCLUSION: GPS/mGPS scoring systems are able to discriminate between three
      risk groups in primarily, but not postoperatively irradiated locally advanced
      head and neck cancer patients.

PMID- 25583137
TI  - A synthetic adenylation-domain-based tRNA-aminoacylation catalyst.
AB  - The incorporation of non-proteinogenic amino acids represents a major challenge
      for the creation of functionalized proteins. The ribosomal pathway is limited to
      the 20-22 proteinogenic amino acids while nonribosomal peptide synthetases
      (NRPSs) are able to select from hundreds of different monomers. Introduced herein
      is a fusion-protein-based design for synthetic tRNA-aminoacylation catalysts
      based on combining NRPS adenylation domains and a small eukaryotic tRNA-binding
      domain (Arc1p-C). Using rational design, guided by structural insights and
      molecular modeling, the adenylation domain PheA was fused with Arc1p-C using
      flexible linkers and achieved tRNA-aminoacylation with both proteinogenic and non
      proteinogenic amino acids. The resulting aminoacyl-tRNAs were functionally
      validated and the catalysts showed broad substrate specificity towards the
      acceptor tRNA. Our strategy shows how functional tRNA-aminoacylation catalysts
      can be created for bridging the ribosomal and nonribosomal worlds. This opens up
      new avenues for the aminoacylation of tRNAs with functional non-proteinogenic
      amino acids. 

PMID- 25583138
TI  - Preventing cardiovascular disease: going beyond conventional risk assessment.

PMID- 25583139
TI  - Cumulative effect of psychosocial factors in youth on ideal cardiovascular health
      in adulthood: the Cardiovascular Risk in Young Finns Study.
AB  - BACKGROUND: The American Heart Association has defined a new metric of ideal
      cardiovascular health as part of its 2020 Impact Goals. We examined whether
      psychosocial factors in youth predict ideal cardiovascular health in adulthood.
      METHODS AND RESULTS: Participants were 477 men and 612 women from the nationwide
      Cardiovascular Risk in Young Finns Study. Psychosocial factors were measured from
      cohorts 3 to 18 years of age at the baseline of the study, and ideal
      cardiovascular health was examined 27 years later in adulthood. The summary
      measure of psychosocial factors in youth comprised socioeconomic factors,
      emotional factors, parental health behaviors, stressful events, self-regulation
      of the child, and social adjustment of the child. There was a positive
      association between a higher number of favorable psychosocial factors in youth
      and greater ideal cardiovascular health index in adulthood (beta=0.16; P<0.001)
      that persisted after adjustment for age, sex, medication use, and cardiovascular
      risk factors in childhood (beta=0.15; P<0.001). The association was monotonic,
      suggesting that each increment in favorable psychosocial factors was associated
      with improvement in cardiovascular health. Of the specific psychosocial factors,
      a favorable socioeconomic environment (beta=0.12; P<0.001) and participants' self
      regulatory behavior (beta=0.07; P=0.004) were the strongest predictors of ideal
      cardiovascular health in adulthood. CONCLUSIONS: The findings suggest a dose
      response association between favorable psychosocial factors in youth and
      cardiovascular health in adulthood, as defined by the American Heart Association
      metrics. The effect seems to persist throughout the range of cardiovascular
      health, potentially shifting the population distribution of cardiovascular health
      rather than simply having effects in a high-risk population.

PMID- 25583140
TI  - Starmerella syriaca f.a., sp. nov., an osmotolerant yeast species isolated from
      flowers in Syria.
AB  - Four strains of a novel asexual ascomycetous yeast species were isolated from
      Malva sp. flowers in Syria. Sequencing of the regions spanning the small subunit,
      5.8S, and the D1/D2 domains of the large subunit ribosomal RNA genes showed that
      the isolates were conspecific. Comparative analysis of these sequences and the
      corresponding sequences of the type strains of ascomycetous yeasts revealed that
      the novel species is phylogenetically related to members of the Starmerella
      clade. Its closest relative is Candida vaccinii. For the new species the name
      Starmerella syriaca is proposed. Its strains are osmotolerant and produce
      pseudohypha-like structures capable of penetrating agar media. The type strain is
      2-1362(T) (=CBS 13909(T) = NCAIM Y.02138(T) = CCY 090-003-001(T)). The GenBank
      accession numbers for its nucleotide sequences are: JX515986 (D1/D2 LSU),
      JX515987 (ITS1-5.8S-ITS2) and JX515988 (SSU). Mycobank: MB 810090. 

PMID- 25583141
TI  - Radiological sinus lift: a new minimally invasive CT-guided procedure for
      maxillary sinus floor elevation in implant dentistry.
AB  - PURPOSE: Implant therapy has become an excellent treatment modality as its
      inception into the modern era of dentistry. However, when patients present with
      advanced atrophy of the maxillary alveolar ridge, the procedure of choice to
      restore the anatomic bone deficiency is surgical maxillary sinus floor elevation
      or sinus lift. The purpose of this study was to describe the CT guided sinus lift
      technique and to illustrate the minimally invasive aspect of this new
      radiological procedure called radiological sinus lift. MATERIAL AND METHODS: For
      this prospective study, 17 cadaver heads which met our inclusion criteria
      (edentulous posterior maxillary sector and bone height less than 5 mm) were
      analyzed using cone beam computed tomography (CBCT) and orthopantomography (OPT).
      CT and sinus endoscopy was used to guide each step in the procedure. The
      radiological sinus lift technique consists of the following four stages:
      Approach. A 14.5 G OstyCut needle was inserted mesial to the canine eminence, and
      manual drilling was performed parallel to the sinus floor. Osteotomy. An inner
      obturator with a blunt tip was introduced to compress bone, to push it in close
      proximity to the sinus membrane and finally to create an osseous window opening
      into the submucosal space. Lifting. The sinus lift was performed using
      hydrodissection with dilute iodinated contrast medium. Filling. The submucosal
      space was then filled with an injection of dilute collagen. Success of the
      radiological sinus lift procedure was defined by the presence of a dome shape
      visible within the maxillary alveolar recess. All cases were imaged
      postoperatively using OPT and maxillary CBCT. RESULTS: Twelve maxillary sinuses
      underwent the radiological sinus floor elevation procedure. A dome shape of the
      Schneiderian membrane was achieved in eight maxillary sinuses (66.7%). All
      failures (n = 4) were caused by mucosal perforation at the time of maxillary
      sinus osteotomy. Mean height of membrane elevation was 12.0 mm, with a mean
      intervention time of 45 min. CONCLUSION: This experimental study evaluates a new
      minimally radiological procedure for maxillary sinus floor elevation, which
      provides an interventional radiological alternative to the classical surgical
      lateral approach and achieves an equivalent success rate to that cited in the
      literature for the surgical approach, a low morbidity and a shorter operating
      time.

PMID- 25583143
TI  - Effects of methoprene, a juvenile hormone analog, on survival of various
      developmental stages, adult emergence, reproduction and behavior of Asian citrus
      psyllid, Diaphorina citri Kuwayama.
AB  - BACKGROUND: The Asian citrus citrus psyllid, Diaphorina citri Kuwayama, transmits
      a bacterium that causes huanglongbing in citrus. Frequent and repeated use of
      neurotoxic insecticides against D. citri has resulted in the development of
      insecticide resistance. We evaluated the effects of the juvenile hormone analog
      methoprene on egg hatch, nymphal development, adult emergence, reproduction and
      behavior of D. citri. RESULTS: Methoprene significantly reduced the viability of
      eggs that were between 0 and 4 days old. Egg hatch of 0-48-h-old and 49-96-h-old
      eggs was 8 and 9%, respectively, when treated with 320 ug mL(-1) of methoprene.
      Methoprene caused significant mortality of first-, third- and fifth-instar D.
      citri nymphs and reduced adult emergence as compared with controls. Methoprene
      caused less than 5% adult emergence when first- and third-instar stages were
      treated, respectively, and less than 40% adult emergence when fifth instars were
      treated. Reduced fertility of females was observed when they emerged from
      methoprene-treated fifth instars. CONCLUSION: Methoprene was effective in
      reducing egg hatch, suppressing nymphal development and decreasing adult
      emergence of D. citri under laboratory conditions. Treatment of fifth instars
      reduced the fertility of females. Methoprene might be a possible tool for
      integrated management of D. citri.

PMID- 25583142
TI  - Microtesla SABRE enables 10% nitrogen-15 nuclear spin polarization.
AB  - Parahydrogen is demonstrated to efficiently transfer its nuclear spin
      hyperpolarization to nitrogen-15 in pyridine and nicotinamide (vitamin B(3)
      amide) by conducting "signal amplification by reversible exchange" (SABRE) at
      microtesla fields within a magnetic shield. Following transfer of the sample from
      the magnetic shield chamber to a conventional NMR spectrometer, the (15)N NMR
      signals for these molecules are enhanced by ~30,000- and ~20,000-fold at 9.4 T,
      corresponding to ~10% and ~7% nuclear spin polarization, respectively. This
      method, dubbed "SABRE in shield enables alignment transfer to heteronuclei" or
      "SABRE-SHEATH", promises to be a simple, cost-effective way to hyperpolarize
      heteronuclei. It may be particularly useful for in vivo applications because of
      longer hyperpolarization lifetimes, lack of background signal, and facile
      chemical-shift discrimination of different species.

PMID- 25583144
TI  - Tactics for teaching evidence-based practice: "moo"ving to greener pastures.

PMID- 25583145
TI  - Patient-provider communications in outpatient clinic settings: a clinic-based
      evaluation of mobile device and multimedia mediated communications for patient
      education.
AB  - BACKGROUND: Many studies have provided evidence of the importance of quality
      provider-patient communications and have suggested improvements to patient
      understanding by using video-based instruction. OBJECTIVE: The objective of this
      study was to understand how mobile information technology assisted video and
      three-dimensional (3D) image instruction, provided by a health care worker,
      influences two categories of outcome: (1) patient understanding of information
      about their condition and detailed medical discharge instructions; and (2)
      patient perceptions and attitudes toward their health care providers, which
      included physicians, nurses, and staff. We hypothesize that video and 3D image
      instruction, provided on a mobile, tablet hardware platform, will improve patient
      understanding about the diagnostic testing, diagnoses, procedures, medications,
      and health topics provided to them. We also propose that use of the tablet/video
      combination will result in improved attitudinal evaluation by patients of their
      providers and the treatment plan. METHODS: This study evaluated a hospital clinic
      based trial (patient N=284) of video and 3D image instruction, provided on a
      mobile, tablet hardware platform, and its potential to improve patient
      understanding about the diagnostic testing, diagnoses, procedures, medications,
      and health topics provided to them. RESULTS: Results showed strong evidence that
      the system was perceived as helpful for improving patient understanding, and that
      it improved communication between physicians and patients (P<.001). The advanced
      age of some patients had no effect on their perceptions of the tablet-based
      mediation. Physician comments provided useful insights on effective use of such
      systems in the future. Implications for further development and future research
      are discussed. CONCLUSIONS: This study added to the body of evidence that
      computer-assisted video instructional systems for patients can improve patient
      understanding of medical instructions from their health care providers and assist
      with patient compliance. In addition, such systems can be appealing to both
      patient and provider.

PMID- 25583146
TI  - [Therapeutic decisions in the treatment of hepatocellular carcinoma and patterns
      of sorafenib use. Results of the international observational GIDEON trial in
      Spain].
AB  - INTRODUCTION: GIDEON is a non-interventional, prospective, international study
      that evaluated the safety of sorafenib in patients with unresectable
      hepatocellular carcinoma (HCC) in daily clinical practice, including Child-Pugh B
      patients. OBJECTIVES: To analyze data collected in Spain on the safety and
      efficacy of sorafenib and treatment patterns. METHODS: Data were collected during
      follow-up on demographic and disease characteristics, the initial dose used,
      treatment-emergent adverse events (AEs) and dose modifications. Overall survival
      was evaluated, as well as time to disease progression. Efficacy and safety were
      analyzed according to the Child-Pugh classification and the initial dose.
      RESULTS: We included 143 patients from 19 Spanish hospitals. A total of 24.5% of
      the patients were Child-Pugh B. An initial dose of 400 mg/12 h was used in 90.9%
      of patients. In Child-Pugh A patients, dose modifications occurred more
      frequently and the treatment duration was longer. The incidence of AEs and drug
      related AEs were similar in Child-Pugh A and B patients, although serious AEs
      were more frequent in Child-Pugh B patients. The most common AEs were diarrhea,
      fatigue and hand-foot skin reactions. The median overall survival was 384 days
      and was higher in Child-Pugh A patients (593 vs. 211 days in Child-Pugh B). The
      median time to disease progression was 177 days, similar in both subgroups.
      CONCLUSION: The safety profile of sorafenib in Spanish patients with unresectable
      HCC is independent of liver function. Child-Pugh status does not seem to
      influence the approach to sorafenib dosage or time to progression but does seem
      to be a strong prognostic factor for survival.

PMID- 25583148
TI  - Validation of the National Early Warning Score in the prehospital setting.
AB  - BACKGROUND: Early intervention and response to deranged physiological parameters
      in the critically ill patient improves outcomes. A National Early Warning Score
      (NEWS) based on physiological observations has been developed for use throughout
      the National Health Service (NHS) in the UK. Although a good predictor of
      mortality and deterioration in inpatients, its performance in the prehospital
      setting is largely untested. This study aimed to assess the validity of the NEWS
      in unselected prehospital patients. METHODS: All clinical observations taken by
      emergency ambulance crews transporting patients to a single hospital were
      collated along with information relating to hospital outcome over a two month
      period. The performance of the NEWS in identifying the endpoints of 48h and 30
      day mortality, intensive care unit (ICU) admission, and a combined endpoint of
      48h mortality or ICU admission was analysed. RESULTS: 1684 patients were
      analysed. All three of the primary endpoints and the combined endpoint were
      associated with higher NEWS scores (p<0.01 for each). The medium-risk NEWS group
      was associated with a statistically significant increase in ICU admission
      (RR=2.466, 95% CI 1.0-6.09), but not in-hospital mortality relative to the low
      risk group. The high risk NEWS group had significant increases in 48h mortality
      (RR 35.32 [10.08-123.7]), 30 day mortality (RR 6.7 [3.79-11.88]), and ICU
      admission (5.43 [2.29-12.89]). Similar results were noted when trauma and non
      trauma patients were analysed separately. CONCLUSIONS: Elevated NEWS among
      unselected prehospital patients is associated with a higher incidence of adverse
      outcomes. Calculation of prehospital NEWS may facilitate earlier recognition of
      deteriorating patients, early involvement of senior Emergency Department staff
      and appropriate critical care.

PMID- 25583147
TI  - Primary meningeal melanocytoma of the sellar region: review of the literature and
      differential diagnosis with special reference to angiographical features.
AB  - PURPOSE: Primary intracranial melanocytomas are rare neoplasms, especially in the
      sellar region. Intracranial melanocytoma is usually a dural-based tumor, fed by
      dural arterial branches in a manner similar to meningioma. Primary sellar
      melanocytoma may be misdiagnosed as hemorrhagic pituitary macroadenoma, spindle
      cell oncocytoma, and intrasellar meningioma. These tumors differ in some
      radiological respects, but are difficult to differentiate preoperatively.
      METHODS: Only five cases of primary sellar/suprasellar melanocytic tumors,
      excluding melanomas have been reported thus far. In this paper, we report an
      instructive new case of a 31-year-old woman presenting with a 2-year history of
      amenorrhea and an intrasellar mass with suprasellar extension, suggestive of
      hemorrhagic pituitary adenoma. RESULTS: Transsphenoidal surgical excision was
      difficult due to extensive bleeding from the lesion, and at the time, the tumor
      could not be diagnosed histopathologically. Six years later, we operated again
      because of tumor regrowth. Angiography revealed a hypervascular tumor, which was
      fed from the dorsal sellar floor. We had difficulty resecting the tumor, but
      achieved total removal. Our case had typical radiographic characteristics of
      melanocytoma, revealed by both magnetic resonance imaging and angiography.
      However, it was difficult to reach a final diagnosis. Further histopathological
      examination, including immunohistochemical and ultrastructural studies, was
      helpful for diagnosis of melanocytoma. CONCLUSIONS: Primary sellar melanocytic
      tumors are derived from melanocytes in the meningeal lining of the sellar floor
      or in the diaphragm sellae, based on both embryological assumptions and the
      clinical findings of our case. We discuss the problems of differential diagnosis
      and management of primary sellar melanocytic tumors.

PMID- 25583149
TI  - A high-throughput ChIP-Seq for large-scale chromatin studies.
AB  - We present a modified approach of chromatin immuno-precipitation followed by
      sequencing (ChIP-Seq), which relies on the direct ligation of molecular barcodes
      to chromatin fragments, thereby permitting experimental scale-up. With Bar-ChIP
      now enabling the concurrent profiling of multiple DNA-protein interactions, we
      report the simultaneous generation of 90 ChIP-Seq datasets without any robotic
      instrumentation. We demonstrate that application of Bar-ChIP to a panel of
      Saccharomyces cerevisiae chromatin-associated mutants provides a rapid and
      accurate genome-wide overview of their chromatin status. Additionally, we
      validate the utility of this technology to derive novel biological insights by
      identifying a role for the Rpd3S complex in maintaining H3K14 hypo-acetylation in
      gene bodies. We also report an association between the presence of intragenic
      H3K4 tri-methylation and the emergence of cryptic transcription in a Set2 mutant.
      Finally, we uncover a crosstalk between H3K14 acetylation and H3K4 methylation in
      this mutant. These results show that Bar-ChIP enables biological discovery
      through rapid chromatin profiling at single-nucleosome resolution for various
      conditions and protein modifications at once. 

PMID- 25583151
TI  - Permanent pacemaker insertion following isolated aortic valve replacement before
      and after the introduction of TAVI.
AB  - BACKGROUND: Permanent pacemaker (PPM) implantation is required in 3-12% of all
      patients undergoing surgical aortic valve replacement (AVR). Our aim was to
      evaluate the contemporary incidence and impact of the introduction of
      transcatheter aortic valve implantation (TAVI) for PPM insertion after isolated
      AVR. METHODS: Since 2004, during a 10-year period, a total of 858 patients
      underwent isolated AVR at our institution. Forty-one patients with PPM before
      operation were excluded from the study and 817 patients were included in the
      statistical analysis. Of these, 20 patients (2.45%) developed significant
      conduction disorders, leading to PPM implantation within 120 days
      postoperatively. Patients were further divided into two groups. Before (Group I:
      June 2004 to September 2008) and after (Group II: October 2008 to May 2014) the
      introduction of the TAVI program. RESULTS: There were 343 patients in Group I and
      475 patients in Group II. The incidence of PPM implantation decreased from 3.79%
      (13 patients) in Group I to 1.47% (seven patients) in Group II (P < 0.001). Risk
      factors for permanent pacing identified by univariate analysis were: Group I
      (before introducing TAVI program), pulmonary hypertension, preoperative anemia,
      age older than 75 years, and previous myocardial infarction. Multivariate
      analysis identified Group I (before introducing TAVI program; P < 0.005; odds
      ratio [OR] 15.2, 95% confidence interval [CI] 6.3-19.9) and pulmonary
      hypertension (P < 0.005; OR 12.5, 95% CI 3.2-18.3) to be significant.
      CONCLUSIONS: Irreversible atrio-ventricular block or symptomatic bradycardia
      requiring PPM implantation is a relatively rare complication. The incidence of
      PPM implantation after isolated surgical AVR decreased in a contemporary setting
      after the introduction of the TAVI program.

PMID- 25583150
TI  - Genome-wide study of mRNA degradation and transcript elongation in Escherichia
      coli.
AB  - An essential part of gene expression is the coordination of RNA synthesis and
      degradation, which occurs in the same cellular compartment in bacteria. Here, we
      report a genome-wide RNA degradation study in Escherichia coli using RNA-seq, and
      present evidence that the stereotypical exponential RNA decay curve obtained
      using initiation inhibitor, rifampicin, consists of two phases: residual RNA
      synthesis, a delay in the interruption of steady state that is dependent on
      distance relative to the mRNA's 5' end, and the exponential decay. This gives a
      more accurate RNA lifetime and RNA polymerase elongation rate simultaneously
      genome-wide. Transcripts typically have a single RNA decay constant along all
      positions, which is distinct between different operons, indicating that RNA
      stability is unlikely determined by local sequences. These measurements allowed
      us to establish a model for RNA processing involving co-transcriptional
      degradation, providing quantitative description of the macromolecular
      coordination in gene expression in bacteria on a system-wide level. 

PMID- 25583152
TI  - Endosalpingiosis of axillary sentinel lymph node: a mimic of metastatic breast
      carcinoma.

PMID- 25583154
TI  - Cascading electron and hole transfer dynamics in a CdS/CdTe core-shell sensitized
      with bromo-pyrogallol red (Br-PGR): slow charge recombination in type II regime.
AB  - Ultrafast cascading hole and electron transfer dynamics have been demonstrated in
      a CdS/CdTe type II core-shell sensitized with Br-PGR using transient absorption
      spectroscopy and the charge recombination dynamics have been compared with those
      of CdS/Br-PGR composite materials. Steady state optical absorption studies
      suggest that Br-PGR forms strong charge transfer (CT) complexes with both the CdS
      QD and CdS/CdTe core-shell. Hole transfer from the photo-excited QD and QD core
      shell to Br-PGR was confirmed by both steady state and time-resolved emission
      spectroscopy. Charge separation was also confirmed by detecting electrons in the
      conduction band of the QD and the cation radical of Br-PGR as measured from
      femtosecond transient absorption spectroscopy. Charge separation in the CdS/Br
      PGR composite materials was found to take place in three different pathways, by
      transferring the photo-excited hole of CdS to Br-PGR, electron injection from the
      photo-excited Br-PGR to the CdS QD, and direct electron transfer from the HOMO of
      Br-PGR to the conduction band of the CdS QD. However, in the CdS/CdTe/Br-PGR
      system hole transfer from the photo-excited CdS to Br-PGR and electron injection
      from the photo-excited Br-PGR to CdS take place after cascading through the CdTe
      shell QD. Charge separation also takes place via direct electron transfer from
      the Br-PGR HOMO to the conduction band of CdS/CdTe. Charge recombination (CR)
      dynamics between the electron in the conduction band of the CdS QD and the Br-PGR
      cation radical were determined by monitoring the bleach recovery kinetics. The CR
      dynamics were found to be much slower in the CdS/CdTe/Br-PGR system than in the
      CdS/Br-PGR system. The formation of the strong CT complex and the separation of
      charges cascading through the CdTe shell help to slow down charge recombination
      in the type II regime. 

PMID- 25583153
TI  - Magnetic resonance estimates of the extent and heterogeneity of scar tissue in
      ICD patients with ischemic cardiomyopathy predict ventricular arrhythmia.
AB  - BACKGROUND: The majority of patients receiving implantable cardioverter
      defibrillator (ICD) implantation under current guidelines never develop sustained
      ventricular arrhythmia; therefore, better markers of risk for sustained
      ventricular tachycardia and/or ventricular fibrillation are needed. OBJECTIVE:
      The purpose of this study was to identify cardiac magnetic resonance arrhythmic
      risk predictors of ischemic cardiomyopathy before ICD implantation. METHODS:
      Forty-three subjects (mean age, 64.5 +/- 11.9 years) with previous myocardial
      infarction who were referred for ICD implantation were evaluated by cardiac
      magnetic resonance imaging (MRI). The MRI protocol included left ventricular
      functional parameter assessment using steady-state free precession and late
      gadolinium enhancement MRI using inversion recovery fast gradient echo. Left
      ventricular functional parameters were measured using cardiac magnetic resonance
      software. Subjects were followed up for 6-46 months, and the events of
      appropriate ICD treatments (shocks and antitachycardia pacing) were recorded.
      RESULTS: Twenty-eight patients experienced 46 spontaneous episodes during a
      median follow-up duration of 30 months. The total myocardial infarct (MI) size
      (18.05 +/- 11.44 g vs 38.83 +/- 19.87 g; P = .0006), MI core (11.63 +/- 7.14 g vs
      24.12 +/- 12.73 g; P = .0002), and infarct gray zone (6.43 +/- 4.64 g vs 14.71 +/
      7.65 g; P = .0004) were significantly larger in subjects who received
      appropriate ICD therapy than in those who did not experience an episode of
      ventricular tachycardia and/or ventricular fibrillation. Multivariate regression
      analyses for the infarct gray zone and MI core adjusted for New York Heart
      Association class, diabetes, and etiology (primary or secondary prevention)
      revealed that the gray zone and MI core were predictors of appropriate ICD
      therapies (P = .0018 and P = .007, respectively). CONCLUSION: The extent of MI
      scar may predict which patients would benefit most from ICD implantation.

PMID- 25583155
TI  - Primary metabolism plays a central role in moulding silicon-inducible brown spot
      resistance in rice.
AB  - Over recent decades, a multitude of studies have shown the ability of silicon
      (Si) to protect various plants against a range of microbial pathogens exhibiting
      different lifestyles and infection strategies. Despite this relative wealth of
      knowledge, an understanding of the action mechanism of Si is still in its
      infancy, which hinders its widespread application for agricultural purposes. In
      an attempt to further elucidate the molecular underpinnings of Si-induced disease
      resistance, we studied the transcriptome of control and Si-treated rice plants
      infected with the necrotrophic brown spot fungus Cochliobolus miyabeanus.
      Analysis of brown spot-infected control plants suggested that C. miyabeanus
      represses plant photosynthetic processes and nitrate reduction in order to
      trigger premature senescence and cause disease. In Si-treated plants, however,
      these pathogen-induced metabolic alterations are strongly impaired, suggesting
      that Si alleviates stress imposed by the pathogen. Interestingly, Si also
      significantly increased photorespiration rates in brown spot-infected plants.
      Although photorespiration is often considered as a wasteful process, recent
      studies have indicated that this metabolic bypass also enhances resistance during
      abiotic stress and pathogen attack by protecting the plant's photosynthetic
      machinery. In view of these findings, our results favour a scenario in which Si
      enhances brown spot resistance by counteracting C. miyabeanus-induced senescence
      and cell death via increased photorespiration. Moreover, our results shed light
      onto the mechanistic basis of Si-induced disease control and support the view
      that, in addition to activating plant immune responses, Si can also reduce
      disease severity by interfering with pathogen virulence strategies. 

PMID- 25583158
TI  - Cognitive decline and dementia: are we getting to the vascular heart of the
      matter?

PMID- 25583157
TI  - Systolic blood pressure variation and mean heart rate is associated with
      cognitive dysfunction in patients with high cardiovascular risk.
AB  - Elevated systolic blood pressure (SBP) correlates to cognitive decline and
      incident dementia. The effects of heart rate (HR), visit to visit HR variation,
      and visit to visit SBP variation are less well established. Patients without
      preexisting cognitive dysfunction (N=24 593) were evaluated according to mean
      SBP, SBP visit to visit variation (coefficient of variation [standard
      deviation/mean*100%], CV), mean HR, and visit to visit HR variation (HR-CV) in
      the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint
      Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects
      with Cardiovascular Disease. Cognitive function was assessed with mini mental
      state examination. Cognitive dysfunction (fall in mini mental state examination
      <=24 points), important cognitive decline (drop of >=5 points), and cognitive
      deterioration (drop of >1 point per year or decline to <24 points) were assessed.
      SBP and HR were measured over 10.7+/-2.2 (mean+/-SD) visits. Mean SBP, mean HR,
      and SBP-CV were associated with cognitive decline, dysfunction, and deterioration
      (all P<0.01, unadjusted). After adjustment, only SBP-CV (P=0.0030) and mean HR
      (P=0.0008) remained predictors for cognitive dysfunction (odds ratios [95%
      confidence intervals], 1.32 [1.10-1.58] for 5th versus 1st quintile of SBP-CV and
      1.40 [1.18-1.66] for 5th versus 1st quintile of mean HR). Similar effects were
      observed for cognitive decline and deterioration. SBP-CV and mean HR showed
      additive effects. In conclusion, SBP-CV and mean HR are independent predictors of
      cognitive decline and cognitive dysfunction in patients at high CV risk. CLINICAL
      TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT
      00153101.

PMID- 25583156
TI  - Epoxyeicosatrienoic acids, hypertension, and kidney injury.

PMID- 25583159
TI  - Brugada syndrome in children.
AB  - Brugada syndrome is an inherited arrhythmia associated with characteristic ST
      elevation in the right precordial leads and sudden cardiac death. The average age
      of sudden cardiac death is 40 years; reported pediatric cases remain rare.
      Genetic testing and increased disease awareness may result in many more children
      being diagnosed with Brugada syndrome. 

PMID- 25583160
TI  - Synthesis and evaluation of novel Tc-99m labeled NGR-containing hexapeptides as
      tumor imaging agents.
AB  - Asparagine-glycine-arginine (NGR)-containing peptides targeting aminopeptidase N
      (APN)/CD13 can be an excellent candidate for targeting ligands in molecular tumor
      imaging. In this study, we developed two NGR-containing hexapeptides, and
      evaluated the diagnostic performance of Tc-99m labeled hexapeptides as molecular
      imaging agents in an HT-1080 fibrosarcoma-bearing murine model. Peptides were
      synthesized using Fmoc solid-phase peptide synthesis. Radiochemical purity of Tc
      99m was evaluated using instant thin-layer chromatography. The uptake of two NGR
      containing hexapeptides within HT-1080 cells was evaluated in vitro. In HT-1080
      fibrosarcoma tumor-bearing mice, gamma images were acquired. A biodistribution
      study was performed to calculate percentage of the injected dose per gram of
      tissue (%ID/g). Two hexapeptides, glutamic acid-cysteine-glycine (ECG)-NGR and
      NGR-ECG were successfully synthesized. After radiolabeling procedures with Tc
      99m, the complexes Tc-99m hexapeptides were prepared in high yield. The uptake of
      Tc-99m ECG-NGR within the tumor cells had been assured by in vitro studies. The
      gamma camera imaging in the murine model showed that Tc-99m ECG-NGR was
      accumulated substantially in the subcutaneously engrafted tumor. However, Tc-99m
      NGR-ECG was accumulated minimally in the tumor. Two NGR-containing hexapeptides,
      ECG-NGR and NGR-ECG were developed as molecular imaging agents to target APN/CD13
      in HT-1080 fibrosarcoma. Tc-99m ECG-NGR showed a significant uptake in the tumor,
      and it is a good candidate for tumor imaging.

PMID- 25583161
TI  - Prevalence and significance of CYP2C19*2 and CYP2C19*17 alleles in a New Zealand
      acute coronary syndrome population.
AB  - BACKGROUND: High on-treatment platelet reactivity has been associated with poor
      outcomes following acute coronary syndromes (ACS). Both the loss of function
      CYP2C19*2 allele and the gain of function CYP2C19*17 allele along with a range of
      clinical characteristics have been associated with variation in the response to
      clopidogrel. AIM: The study aims to examine the frequency of CYP2C19 variants and
      understand the factors associated with on-treatment platelet reactivity in a New
      Zealand ACS population. METHODS: We prospectively enrolled 312 ACS patients. We
      collected clinical characteristics and measured on-treatment platelet reactivity
      using two validated point-of-care assays, VerifyNow and Multiplate. DNA was
      extracted and CYP2C19*2 and *17 alleles were identified using real-time
      polymerase chain reaction. RESULTS: CYP2C19*2 or CYP2C19*17 alleles were observed
      in 101 (32%) and 106 (34%) of patients, respectively, with significant
      differences in distribution by ethnicity. In Maori and Pacific Island patients,
      47% (confidence interval (CI) 31-63%) had CYP2C19*2 and 11% (CI 4-19%) CYP2C19*17
      compared with 26% (CI 19-32%) and 41% (CI 32-49%) in white people. Carriage of
      CYP2C19*2 alleles was associated with higher levels of platelet reactivity
      measured by either assay, but we observed no relationship between platelet
      reactivity and CYP2C19*17. In multivariate analysis diabetes, clopidogrel dose
      and CYP2C19*2 status were all significant independent predictors of platelet
      reactivity. CONCLUSIONS: Both CYP2C19*2 and *17 were common in a New Zealand ACS
      population, with CYP2C19*2 observed in almost half the Maori and Pacific Island
      patients. CYP2C19*2, diabetes and clopidogrel dose were independent contributors
      to on-treatment platelet reactivity.

PMID- 25583162
TI  - Impact of formal teaching on medical documentation by interns in an emergency
      department in a Queensland teaching hospital.
AB  - OBJECTIVES: This study's objective was to determine whether tuition in medical
      documentation enhanced the ability of emergency medicine interns to produce
      effective medical records. METHODS: The study adopted a case control design,
      using a retrospective document audit methodology, following an education
      intervention during the 'More Learning for Interns in Emergency' (MoLIE)
      programme. It was conducted in a tertiary hospital that supports five 10 week
      rotations of 12 interns each year (n = 60). Controls were drawn from records
      written in March 2012 and cases from March 2013. A total of 250 medical records
      written by interns were audited, 125 from each year. RESULTS: Three categories of
      documentation were investigated: patient characteristics, clinical impressions
      and management plan using a purpose-designed score sheet. Three individual items
      (differential diagnosis [DDX], Support and Impressions [Impress]) showed
      significant improvement. The proportion of excellent scores for DDX increased by
      50% from 40.8% to 61.6%. A chi(2) test for independence (with Yates continuity
      correction) indicated a significant association between the intervention and
      subsequent score (X(2) [1, n = 250] = 10.006, P < 0.001, phi -0.208). For
      Impress, a 48% increase in excellent scores was seen (39.2% to 58.4%). A chi(2)
      test for independence indicated a significant association between the
      intervention and subsequent score (X(2) [2, n = 250] = 11.249, P = 0.004,
      Cramer's V 0.212). The variable Support also improved (X(2) [2, n = 250] = 8.297,
      P = 0.012, Cramer's V 0.189) with the number of excellent scores increasing from
      37.6% to 48.0%. CONCLUSION: The study demonstrated that documentation of clinical
      notes by interns can be enhanced by formal tuition.

PMID- 25583163
TI  - SF-36 healty survey on psoriasis quality-of-life: a study of 414 Taiwanese
      patients.
AB  - Psoriasis is a chronic debilitating disease that impairs patients' physical and
      social functioning. The assessment of health-related quality of life (HRQoL)
      provides a comprehensive insight into the actual disease burden that are not
      captured by the traditional clinical parameters. The objective of this study is
      to identify factors that may impact patients' HRQoL. We conducted a cross
      sectional study, recruiting a total of 414 psoriasis vulgaris patients between
      January 2008 and December 2011. Our study found no significant correlation
      between disease severity or duration of psoriasis with HRQoL. Female patients
      have poorer HRQoL. Psoriatic arthritis, nail involvement, burning and itching
      sensation have a detrimental effect on HRQoL. This study highlighted that
      specific disease-associated symptoms such as itching and burning sensation, nail
      involvement and/or concomitant arthritis were important factors that may impact
      patients' HRQoL devoid of clinical severity. Physicians should carefully consider
      these factors when treating psoriasis patients. 

PMID- 25583165
TI  - Hepatitis C Virus Infection Is Systemic: Meeting Additional Goals.

PMID- 25583164
TI  - Sofosbuvir and Ribavirin for Treatment of Chronic Hepatitis C in Patients
      Coinfected With Hepatitis C Virus and HIV: The Impact on Patient-Reported
      Outcomes.
AB  - BACKGROUND: Sofosbuvir-containing regimens have been approved for treatment of
      hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected
      patients. We assessed the effect of treatment with sofosbuvir and ribavirin on
      patient-reported outcomes (PROs) in individuals with HIV/HCV coinfection.
      METHODS: HIV/HCV-coinfected patients were treated for 12 or 24 weeks with
      sofosbuvir and ribavirin. Matched HCV-monoinfected controls were also evaluated.
      All subjects completed standard PRO questionnaires before, during, and after
      treatment. RESULTS: Included were 497 participants from the PHOTON-1 and PHOTON-2
      clinical trials. At baseline, more impairment in PRO scores was noted in HIV/HCV
      coinfected patients, compared with HCV-monoinfected patients. During treatment,
      moderate decrements in PRO scores (change, up to -6.8% on a 0%-100% scale; P =
      .0053) were experienced regardless of treatment duration and were similar to
      those for HCV-monoinfected patients (all P > .05). In 413 HIV/HCV-coinfected
      patients with a virologic response sustained for 12 weeks after treatment
      cessation, most PRO scores improved (change, up to +7.6%; P < .0001), similar to
      findings for HCV-monoinfected patients. In multivariate analysis, in addition to
      clinico-demographic predictors, coinfection with HIV was associated with PRO
      impairment at baseline (beta, up to -7.6%; P < .002) but not with treatment
      emergent changes in PRO scores (all P > .05). CONCLUSIONS: Patients with HIV/HCV
      coinfection tolerate interferon-free sofosbuvir-based anti-HCV regimens well and,
      despite the presence of some baseline impairment, have treatment-emergent changes
      in PRO scores that are similar to those of patients with HCV monoinfection.
      CLINICAL TRIALS REGISTRATION: NCT01667731 (PHOTON-1), NCT01783678 (PHOTON-2),
      NCT01604850 (FUSION), and NCT01682720 (VALENCE).

PMID- 25583166
TI  - The Serine Protease Pic From Enteroaggregative Escherichia coli Mediates Immune
      Evasion by the Direct Cleavage of Complement Proteins.
AB  - Enteroaggregative and uropathogenic Escherichia coli, Shigella flexneri 2a, and
      the hybrid enteroaggregative/Shiga toxin-producing E. coli strain (O104:H4) are
      important pathogens responsible for intestinal and urinary tract infections, as
      well as sepsis and hemolytic uremic syndrome. They have in common the production
      of a serine protease called Pic. Several biological roles for Pic have been
      described, including protection of E. coli DH5alpha from complement-mediated
      killing. Hereby we showed that Pic significantly reduces complement activation by
      all 3 pathways. Pic cleaves purified C3/C3b and other proteins from the classic
      and lectin pathways, such as C4 and C2. Cleavage fragments of C3, C4, and C2 were
      also observed with HB101(pPic1) culture supernatants, and C3 cleavage sites were
      mapped by fluorescence resonance energy transfer peptides. Experiments using
      human serum as a source of complement proteins confirmed Pic proteolytic activity
      on these proteins. Furthermore, Pic works synergistically with the human
      complement regulators factor I and factor H, promoting inactivation of C3b. In
      the presence of both regulators, further degradation of C3 alpha' chain was
      observed. Therefore, Pic may contribute to immune evasion of E. coli and S.
      flexneri, favoring invasiveness and increasing the severity of the disorders
      caused by these pathogens. 

PMID- 25583167
TI  - Human Influenza A Virus-Specific CD8+ T-Cell Response Is Long-lived.
AB  - Animal and human studies have demonstrated the importance of influenza A virus
      (IAV)-specific CD8(+) cytotoxic T lymphocytes (CTLs) in heterosubtypic cross
      protective immunity. Using peripheral blood mononuclear cells obtained
      intermittently from healthy HLA-typed blood donors between 1999 and 2012, we were
      able to demonstrate that IAV-specific CTLs are long-lived. Intercurrent IAV
      infections transiently increase the frequency of functionally distinct subsets of
      IAV-specific CTLs, in particular effector and effector memory T cells. 

PMID- 25583168
TI  - Differential Reduction in Monocyte Activation and Vascular Inflammation With
      Integrase Inhibitor-Based Initial Antiretroviral Therapy Among HIV-Infected
      Individuals.
AB  - BACKGROUND: Little is known about how different antiretrovirals effect
      inflammation and monocyte activation in human immunodeficiency virus (HIV)
      infection. METHODS: We examined plasma specimens obtained during a randomized,
      double-blinded trial in antiretroviral therapy (ART)-naive HIV-infected adults
      which compared the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir
      disoproxil fumarate (EVG/c/FTC/TDF) with that of
      efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). From a
      random sample achieving an HIV type 1 RNA load of <50 copies/mL by week 48,
      changes over 24 and 48 weeks in levels of biomarkers of monocyte activation
      (soluble CD14 [sCD14] and soluble CD163 [sCD163]), systemic inflammation (soluble
      tumor necrosis factor alpha receptor I [sTNF-RI], interleukin 6 [IL-6], and high
      sensitivity C-reactive protein [hsCRP]), and vascular inflammation (lipoprotein
      associated phospholipase A2 [Lp-PLA2]) were compared. Multivariable linear
      regression was used. RESULTS: A total of 200 participants were included.
      Significant differences favoring EVG/c/FTC/TDF were noted for changes in sCD14,
      hsCRP, and Lp-PLA2 levels. Factors independently associated with a larger
      decrease in the sCD14 level included random assignment to receive EVG/c/FTC/TDF,
      higher baseline sCD14 level, and larger decreases in hsCRP and sCD163 levels;
      factors associated with a larger Lp-PLA2 decrease included higher baseline Lp
      PLA2 and IL-6 levels, smaller increases in total cholesterol and triglycerides
      levels, a larger decrease in the sCD14 level, and a smaller decrease in the
      sCD163 level. CONCLUSIONS: EVG/c/FTC/TDF led to greater decreases in sCD14,
      hsCRP, and Lp-PLA2 levels, compared with EFV/FTC/TDF. Randomization group
      independently predicted the change in sCD14 level, and changes in monocyte
      activation independently predicted the change in Lp-PLA2 level. There appears to
      be a more favorable effect of the integrase inhibitor EVG over efavirenz on
      immune activation, which may affect vascular inflammation.

PMID- 25583169
TI  - Immediate T-Helper 17 Polarization Upon Triggering CD11b/c on HIV-Exposed
      Dendritic Cells.
AB  - Early on in human immunodeficiency virus (HIV) type 1 infection, gut T-helper
      (Th) 17 cells are massively depleted leading eventually to compromised intestinal
      barrier function and excessive immune activation. In contrast, the functional
      Th17 cell compartment of the gut is well-maintained in nonpathogenic simian
      immunodeficiency virus infection as well as HIV-1 long-term nonprogressors. Here,
      we show that dendritic cells (DCs) loaded with HIV-1 bearing high surface
      complement levels after incubation in plasma from HIV-infected individuals
      secreted significantly higher concentrations of Th17-polarizing cytokines than
      DCs exposed to nonopsonized HIV-1. The enhanced Th17-polarizing capacity of in
      vitro-generated and BDCA-1(+) DCs directly isolated from blood was linked to
      activation of ERK. In addition, C3a produced from DCs exposed to complement
      opsonized HIV was associated with the higher Th17 polarization. Our in vitro and
      ex vivo data, therefore, indicate that complement opsonization of HIV-1
      strengthens DC-mediated antiviral immune functions by simultaneously triggering
      Th17 expansion and intrinsic C3 formation via DC activation. 

PMID- 25583171
TI  - Inflammation in Chronic HIV Infection: What Can We Do?

PMID- 25583170
TI  - The cutaneous microbiome in outpatients presenting with acute skin abscesses.
AB  - BACKGROUND: Previous studies have demonstrated an association between antibiotic
      use and the development of skin abscesses. We tested the hypothesis that
      alterations in the composition of the cutaneous microbiota may predispose
      individuals to skin abscesses. METHODS: We studied 25 patients with skin
      abscesses and 25 age-matched controls, who each completed a questionnaire. Skin
      swab samples were obtained for DNA analysis from 4 sites around the abscess site
      (hereafter, "peri-abscess specimens") and from similar sites on the patient's
      contralateral side and on healthy control subjects. DNA was extracted and
      analyzed by quantitative polymerase chain reaction (qPCR) and high-throughput
      sequencing. The purulent abscess drainage was sent for culture. RESULTS: Fifteen
      patients with abscess were infected with Staphylococcus aureus. Use of nuc qPCR
      to quantitate S. aureus revealed a significantly greater frequency of positive
      results for peri-abscess and contralateral skin samples, compared with control
      skin specimens. Analysis of community structure showed greater heterogeneity in
      the control samples than in the peri-abscess and contralateral samples.
      Metagenomic analysis detected significantly more predicted genes related to
      metabolic activity in the peri-abscess specimens than in the control samples.
      CONCLUSIONS: The peri-abscess microbiome was similar to the contralateral
      microbiome, but both microbiomes differed from that for control patients. Host
      characteristics affecting microbial populations might be important determinants
      of abscess risk.

PMID- 25583172
TI  - New medical device regulations ahead - what does that mean for arthroplasty
      registers?

PMID- 25583173
TI  - The hydrolysed products of iridoid glycosides can enhance imatinib mesylate
      induced apoptosis in human myeloid leukaemia cells.
AB  - Several studies have demonstrated that deregulated activation of signal
      transducer and activator of transcription 3 (STAT3) has been associated with
      survival, proliferation, chemoresistance and angiogenesis of tumour cells. Thus,
      inhibition of STAT3 expression could be a potent therapeutic approach for cancer
      treatment. Using several leukaemia cell lines, the effect of the hydrolysed
      catalpol (H-catalpol) and hydrolysed-aucubin (H-aucubin) products on the STAT3
      signalling pathway, inhibition of BCR-ABL activation, cellular proliferation and
      potentiation of imatinib mesylate-induced apoptosis was investigated. We found
      that iridoid glycosides (catalpol and aucubin) did not exert any cytotoxicity in
      the tumour cells, whereas both H-catalpol and H-aucubin exhibited significant
      cytotoxic effects on K562 human myeloid leukaemia cells. Indeed, H-catalpol and H
      aucubin down-regulated BCR-ABL phosphorylation and inhibited constitutive STAT3
      activation through abrogating upstream JAK2 and c-Src and constitutive STAT5
      activation leading to apoptosis through caspase-3 activation. Hydrolysed-catalpol
      enhanced the apoptosis induced by imatinib mesylate and this correlated with down
      regulation of gene products that mediate cell proliferation (cyclin D1), and cell
      survival (Bcl-2, Bcl-xL and survivin); all known to be regulated by the STAT3.
      Overall, our results provide novel insight into the role of hydrolysed iridoids
      in potentially treating leukaemia through the modulation of STAT3 signalling
      pathway.

PMID- 25583174
TI  - Production and characterization of active recombinant interleukin-12/eGFP fusion
      protein in stably-transfected DF1 chicken cells.
AB  - The adjuvant activity of chicken interleukin-12 (chIL-12) protein has been
      described as similar to that of mammalian IL-12. Recombinant chIL-12 can be
      produced using several methods, but chIL-12 production in eukaryotic cells is
      lower than that in prokaryotic cells. Stimulating compounds, such as dimethyl
      sulfoxide (DMSO), can be added to animal cell cultures to overcome this drawback.
      In this study, we constructed a cell line, DF1/chIL-12 which stably expressed a
      fusion protein, chIL-12 and enhanced green fluorescent protein (eGFP) connected
      by a (G4 S)3 linker sequence. Fusion protein production was increased when cells
      were cultured in the presence of DMSO. When 1 * 10(6) DF1/chIL-12 cells were
      inoculated in a T-175 flask containing 30 mL of media, incubated for 15 h, and
      further cultivated in the presence of 4% DMSO for 48 h, the production of total
      fusion protein was mostly enhanced compared with the production of total fusion
      protein by using cell lysates induced with DMSO at other concentrations. The
      concentrations of the unpurified and purified total fusion proteins in cell
      lysates were 2,781 +/- 2.72 ng mL(-1) and 2,207 +/- 3.28 ng mL(-1) ,
      respectively. The recovery rate was 79%. The fusion protein stimulated chicken
      splenocytes to produce IFN-gamma, which was measured using an enzyme-linked
      immunosorbent assay, in the culture supernatant, indicating that treating
      DF1/chIL-12 cells with DMSO or producing chIL-12 in a fusion protein form does
      not have adverse effects on the bioactivity of chIL-12.

PMID- 25583175
TI  - Effect of 8-oxoguanine glycosylase deficiency on aflatoxin B1 tumourigenicity in
      mice.
AB  - The mycotoxin aflatoxin B1 (AFB1) may initiate cancer by causing oxidatively
      damaged DNA, specifically by causing 8-oxo-7,8-dihydro-2'-deoxyguanosine (8
      oxodG) lesions. Base excision repair removes these lesions, with 8-oxoguanine
      glycosylase (OGG1) being the rate-limiting enzyme. The aim of this study was to
      determine the effect of ogg1 deficiency on AFB1-induced oxidatively damaged DNA
      and tumourigenesis. Female wild-type, heterozygous and homozygous ogg1 null mice
      were given a single dose of 50mg/kg AFB1 or 40 ul dimethyl sulfoxide (DMSO) ip.
      Neither ogg1 genotype nor AFB1 treatment affected levels of oxidised guanine in
      lung or liver 2h post-treatment. AFB1-treated ogg1 null mice showed exacerbated
      weight loss and mortality relative to DMSO-treated ogg1 null mice, but AFB1
      treatment did not significantly increase lung or liver tumour incidence compared
      with controls, regardless of ogg1 genotype. Suspect lung masses from three of the
      AFB1-treated mice were adenomas, and masses from two of the mice were
      osteosarcomas. No osteosarcomas were observed in DMSO-treated mice. All liver
      masses from AFB1-treated mice were adenomas, and one also contained a
      hepatocellular carcinoma. In DNA from the lung tumours, the K-ras mutation
      pattern was inconsistent with initiation by AFB1. In conclusion, ogg1 status did
      not have a significant effect on AFB1-induced oxidatively damaged DNA or
      tumourigenesis, but deletion of one or both alleles of ogg1 did increase
      susceptibility to other aspects of AFB1 toxicity. 

PMID- 25583176
TI  - Arbuscular mycorrhizal dialogues: do you speak 'plantish' or 'fungish'?
AB  - Plants rely on their associated microbiota for crucial physiological activities;
      realization of this interaction drives research to understand inter-domain
      communication. This opinion article focuses on the arbuscular mycorrhizal (AM)
      symbiosis, which involves the Glomeromycota, fungi that can form a symbiosis with
      most plants. Here we propose the hypothesis that the molecules involved in inter
      kingdom symbiotic signaling, such as strigolactones, cutin monomers, and chitin
      related molecules, also have key roles in development, originally unrelated to
      symbiosis. Thus, the symbiotic role of these molecules relies on the co-evolved
      capacity of the AM partners to perceive and interpret them as symbiotic signals. 

PMID- 25583177
TI  - Molecular subtypes of clear cell renal cell carcinoma are associated with
      sunitinib response in the metastatic setting.
AB  - PURPOSE: Selecting patients with metastatic clear-cell renal cell carcinoma (m
      ccRCC) who might benefit from treatment with targeted tyrosine kinase inhibitors
      (TKI) is a challenge. Our aim was to identify molecular markers associated with
      outcome in patients with m-ccRCC treated with sunitinib. EXPERIMENTAL DESIGN: We
      performed global transcriptome analyses on 53 primary resected ccRCC tumors from
      patients who developed metastatic disease and were treated with first-line
      sunitinib. We also determined chromosome copy-number aberrations, methylation
      status, and gene mutations in von Hippel-Lindau and PBRM1. Molecular data were
      analyzed in relation with response rate (RR), progression-free survival (PFS),
      and overall survival (OS). Validation was performed in 47 additional ccRCC
      samples treated in first-line metastatic setting with sunitinib. RESULTS:
      Unsupervised transcriptome analysis identified 4 robust ccRCC subtypes (ccrcc1 to
      4) related to previous molecular classifications that were associated with
      different responses to sunitinib treatment. ccrcc1/ccrcc4 tumors had a lower RR
      (P = 0.005) and a shorter PFS and OS than ccrcc2/ccrcc3 tumors (P = 0.001 and
      0.0003, respectively). These subtypes were the only significant covariate in the
      multivariate Cox model for PFS and OS (P = 0.017 and 0.006, respectively).
      ccrcc1/ccrcc4 tumors were characterized by a stem-cell polycomb signature and CpG
      hypermethylation, whereas ccrcc3 tumors, sensitive to sunitinib, did not exhibit
      cellular response to hypoxia. Moreover, ccrcc4 tumors exhibited sarcomatoid
      differentiation with a strong inflammatory, Th1-oriented but suppressive immune
      microenvironment, with high expression of PDCD1 (PD-1) and its ligands.
      CONCLUSIONS: ccRCC molecular subtypes are predictive of sunitinib response in
      metastatic patients, and could be used for personalized mRCC treatment with TKIs,
      demethylating or immunomodulatory drugs.

PMID- 25583179
TI  - Guest editorial: mood disorders-preclinical, clinical and translational aspects.

PMID- 25583180
TI  - The pain of pain: challenges of animal behavior models.
AB  - Berend Olivier has had a long-standing interest in the utility of animal models
      for a wide variety of therapeutic indications. His work has spanned multiple
      types of models, blending ethological, or species typical and naturalistic
      behaviors, along with methodologies based on learned behavior. He has
      consistently done so, from an analytical as well as predictive perspective, and
      has made multiple contributions while working in both the pharmaceutical industry
      and within an academic institution. Although focused primarily on psychiatric
      disorders, Berend has conducted research in the area of pain in humans and in
      animals, demonstrating an expansive appreciation for the breadth, scope and
      significance of the science and applications of the discipline of pharmacology to
      these diverse areas. This review focuses on the use of animal models in pain
      research from the perspective of the long-standing deficiencies in the
      development of therapeutics in this area and from a preclinical perspective where
      the translational weaknesses have been quite problematic. The challenges
      confronting animal models of pain, however, are not unique to this area of
      research, as they cut across several therapeutic areas. Despite the deficiencies,
      failures and concerns, existing animal models of pain continue to be of
      widespread use and are essential to progress in pain research as well as in other
      areas. Although not focusing on specific animal models of pain, this paper seeks
      to examine general issues facing the use of these models. It does so by exploring
      alternative approaches which capture recent developments, which build upon
      principles and concepts we have learned from Berend's contributions, and which
      provide the prospect of helping to address the absence of novel therapeutics in
      this area.

PMID- 25583181
TI  - Two-Electron Transfer Pathways.
AB  - The frontiers of electron-transfer chemistry demand that we develop theoretical
      frameworks to describe the delivery of multiple electrons, atoms, and ions in
      molecular systems. When electrons move over long distances through high barriers,
      where the probability for thermal population of oxidized or reduced bridge
      localized states is very small, the electrons will tunnel from the donor (D) to
      acceptor (A), facilitated by bridge-mediated superexchange interactions. If the
      stable donor and acceptor redox states on D and A differ by two electrons, it is
      possible that the electrons will propagate coherently from D to A. While
      structure-function relations for single-electron superexchange in molecules are
      well established, strategies to manipulate the coherent flow of multiple
      electrons are largely unknown. In contrast to one-electron superexchange, two
      electron superexchange involves both one- and two-electron virtual intermediate
      states, the number of virtual intermediates increases very rapidly with system
      size, and multiple classes of pathways interfere with one another. In the study
      described here, we developed simple superexchange models for two-electron
      transfer. We explored how the bridge structure and energetics influence
      multielectron superexchange, and we compared two-electron superexchange
      interactions to single-electron superexchange. Multielectron superexchange
      introduces interference between singly and doubly oxidized (or reduced) bridge
      virtual states, so that even simple linear donor-bridge-acceptor systems have
      pathway topologies that resemble those seen for one-electron superexchange
      through bridges with multiple parallel pathways. The simple model systems studied
      here exhibit a richness that is amenable to experimental exploration by
      manipulating the multiple pathways, pathway crosstalk, and changes in the number
      of donor and acceptor species. The features that emerge from these studies may
      assist in developing new strategies to deliver multiple electrons in condensed
      phase redox systems, including multiple-electron redox species,
      multimetallic/multielectron redox catalysts, and multiexciton excited states. 

PMID- 25583178
TI  - The dark side of emotion: the addiction perspective.
AB  - Emotions are "feeling" states and classic physiological emotive responses that
      are interpreted based on the history of the organism and the context. Motivation
      is a persistent state that leads to organized activity. Both are intervening
      variables and intimately related and have neural representations in the brain.
      The present thesis is that drugs of abuse elicit powerful emotions that can be
      interwoven conceptually into this framework. Such emotions range from pronounced
      euphoria to a devastating negative emotional state that in the extreme can create
      a break with homeostasis and thus an allostatic hedonic state that has been
      considered key to the etiology and maintenance of the pathophysiology of
      addiction. Drug addiction can be defined as a three-stage cycle
      binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation
      that involves allostatic changes in the brain reward and stress systems. Two
      primary sources of reinforcement, positive and negative reinforcement, have been
      hypothesized to play a role in this allostatic process. The negative emotional
      state that drives negative reinforcement is hypothesized to derive from
      dysregulation of key neurochemical elements involved in the brain incentive
      salience and stress systems. Specific neurochemical elements in these structures
      include not only decreases in incentive salience system function in the ventral
      striatum (within-system opponent processes) but also recruitment of the brain
      stress systems mediated by corticotropin-releasing factor (CRF), dynorphin-kappa
      opioid systems, and norepinephrine, vasopressin, hypocretin, and substance P in
      the extended amygdala (between-system opponent processes). Neuropeptide Y, a
      powerful anti-stress neurotransmitter, has a profile of action on compulsive-like
      responding for drugs similar to a CRF1 receptor antagonist. Other stress buffers
      include nociceptin and endocannabinoids, which may also work through interactions
      with the extended amygdala. The thesis argued here is that the brain has specific
      neurochemical neurocircuitry coded by the hedonic extremes of pleasant and
      unpleasant emotions that have been identified through the study of opponent
      processes in the domain of addiction. These neurochemical systems need to be
      considered in the context of the framework that emotions involve the specific
      brain regions now identified to differentially interpreting emotive physiological
      expression. 

PMID- 25583182
TI  - Ultrasound-guided percutaneous irrigation in rotator cuff calcific tendinopathy:
      what is the evidence? A systematic review with proposals for future reporting.
AB  - OBJECTIVES: We performed a systematic review of current evidence regarding
      ultrasound-guided percutaneous irrigation of calcific tendinopathy (US-PICT) in
      the shoulder aimed to: assess different published techniques; evaluate clinical
      outcome in a large combined cohort; and propose suggestions for homogeneous
      future reporting. METHODS: Cochrane Collaboration for Systematic Reviews of
      Interventions Guidelines were followed. We searched MEDLINE/MEDLINE In
      Process/EMBASE/Cochrane databases from 1992-2013 using the keywords 'ultrasound,
      shoulder, needling, calcification, lavage, rotator cuff' combined in appropriate
      algorithms. References of resulting papers were also screened. Risk of bias was
      assessed with a modified Newcastle-Ottawa Scale. RESULTS: Of 284 papers found, 15
      were included, treating 1,450 shoulders in 1,403 patients (females, n = 838; mean
      age interval 40-63 years). There was no exclusion due to risk of bias.
      CONCLUSIONS: US-PICT of rotator cuff is a safe and effective procedure, with an
      estimated average 55% pain improvement at an average of 11 months, with a 10%
      minor complication rate. No evidence exists in favour of using a specific
      size/number of needles. Imaging follow-up should not be used routinely. Future
      studies should aim at structural uniformity, including the use of the Constant
      Score to assess outcomes and 1-year minimum follow-up. Alternatives to steroid
      injections should also be explored. KEY POINTS: * US-PICT of rotator cuff is a
      safe and effective procedure. * On average 55% pain improvement with 10% minor
      complication rate. * No evidence exists in favour of using a specific size/number
      of needles. * Future need to assess outcome using Constant Score with 1-year
      minimum follow-up.

PMID- 25583183
TI  - Neurofilament light mutation causes hereditary motor and sensory neuropathy with
      pyramidal signs.
AB  - To identify novel mutations causing hereditary motor and sensory neuropathy
      (HMSN) with pyramidal signs, a variant of Charcot-Marie-Tooth disease (CMT), we
      screened 28 CMT and related genes in four members of an affected Japanese family.
      Clinical features included weakness of distal lower limb muscles, foot deformity,
      and mild sensory loss, then late onset of progressive spasticity.
      Electrophysiological studies revealed widespread neuropathy. Electron microscopic
      analysis showed abnormal mitochondria and mitochondrial accumulation in the
      neurons and Schwann cells. Brain magnetic resonance imaging (MRI) revealed an
      abnormally thin corpus callosum. In all four, microarrays detected a novel
      heterozygous missense mutation c.1166A>G (p.Y389C) in the gene encoding the light
      chain neurofilament protein (NEFL), indicating that NEFL mutations can result in
      a HMSN with pyramidal signs phenotype.

PMID- 25583184
TI  - Effect of hand paddles and parachute on butterfly coordination.
AB  - This study investigated the effects of hand paddles, parachute and hand paddles
      plus parachute on the inter-limb coordination of butterfly swimming. Thirteen
      male swimmers were evaluated in four random maximal intensity conditions: without
      equipment, with hand paddles, with parachute and with hand paddles + parachute.
      Arm and leg stroke phases were identified by 2D video analysis to calculate the
      total time gap (T1: time between hands' entry in the water and high break-even
      point of the first undulation; T2: time between the beginning of the hand's
      backward movement and low break-even point of the first undulation; T3: time
      between the hand's arrival in a vertical plane to the shoulders and high break
      even point of the second undulation; T4: time between the hand's release from the
      water and low break-even point of the second undulation). The swimming velocity
      was reduced and T1, T2 and T3 increased in parachute and hand paddles +
      parachute. No changes were observed in T4. Total time gap decreased in parachute
      and hand paddles + parachute. It is concluded that hand paddles do not influence
      the arm-to-leg coordination in butterfly, while parachute and hand paddles +
      parachute do change it, providing a greater propulsive continuity. 

PMID- 25583187
TI  - Do we need to monitor cardiac output in spontaneously breathing patients?

PMID- 25583186
TI  - Partial rescue of some features of Huntington Disease in the genetic absence of
      caspase-6 in YAC128 mice.
AB  - Huntington Disease (HD) is a progressive neurodegenerative disease caused by an
      elongated CAG repeat in the huntingtin (HTT) gene that encodes a polyglutamine
      tract in the HTT protein. Proteolysis of the mutant HTT protein (mHTT) has been
      detected in human and murine HD brains and is implicated in the pathogenesis of
      HD. Of particular importance is the site at amino acid (aa) 586 that contains a
      caspase-6 (Casp6) recognition motif. Activation of Casp6 occurs
      presymptomatically in human HD patients and the inhibition of mHTT proteolysis at
      aa586 in the YAC128 mouse model results in the full rescue of HD-like phenotypes.
      Surprisingly, Casp6 ablation in two different HD mouse models did not completely
      prevent the generation of this fragment, and therapeutic benefits were limited,
      questioning the role of Casp6 in the disease. We have evaluated the impact of the
      loss of Casp6 in the YAC128 mouse model of HD. Levels of the mHTT-586 fragment
      are reduced but not absent in the absence of Casp6 and we identify caspase 8 as
      an alternate enzyme that can generate this fragment. In vivo, the ablation of
      Casp6 results in a partial rescue of body weight gain, normalized IGF-1 levels, a
      reversal of the depression-like phenotype and decreased HTT levels. In the
      YAC128/Casp6-/- striatum there is a concomitant reduction in p62 levels, a marker
      of autophagic activity, suggesting increased autophagic clearance. These results
      implicate the HTT-586 fragment as a key contributor to certain features of HD,
      irrespective of the enzyme involved in its generation. 

PMID- 25583188
TI  - Evaluation of the utility of the Vigileo FloTrac(TM) , LiDCO(TM) , USCOM and
      CardioQ(TM) to detect hypovolaemia in conscious volunteers: a proof of concept
      study.
AB  - It is important to detect and treat hypovolaemia; however, detection is
      particularly challenging in the conscious, spontaneously breathing patient. Eight
      healthy male volunteers were monitored using four minimally invasive monitors:
      Vigileo FloTrac(TM) ; LiDCOrapid(TM) ; USCOM 1A; and CardioQ(TM) oesophageal
      Doppler. Monitor output and clinical signs were recorded during incremental
      venesection of 2.5% estimated blood volume aliquots to a total of 20% blood
      volume removed. A statistically significant difference from baseline stroke
      volume was detected after 2.5% blood loss using the LiDCO (p = 0.007), 7.5% blood
      loss using the USCOM (p = 0.019), and 12.5% blood loss using the CardioQ (p =
      0.046) and the FloTrac (p = 0.028). Receiver operator characteristic curves for
      predicting > 10% blood loss had areas under the curve of 0.68-0.82. The minimally
      invasive cardiac output devices tested can detect blood loss by a reduction in
      stroke volume in awake volunteers, and may have a role in guiding fluid
      replacement in conscious patients with suspected hypovolaemia.

PMID- 25583185
TI  - Molecular basis of neurodegeneration and neurodevelopmental defects in Menkes
      disease.
AB  - ATP7A mutations impair copper metabolism resulting in three distinct genetic
      disorders in humans. These diseases are characterized by neurological phenotypes
      ranging from intellectual disability to neurodegeneration. Severe ATP7A loss-of
      function alleles trigger Menkes disease, a copper deficiency condition where
      systemic and neurodegenerative phenotypes dominate clinical outcomes. The
      pathogenesis of these manifestations has been attributed to the hypoactivity of a
      limited number of copper-dependent enzymes, a hypothesis that we refer as the
      oligoenzymatic pathogenic hypothesis. This hypothesis, which has dominated the
      field for 25 years, only explains some systemic Menkes phenotypes. However, we
      argue that this hypothesis does not fully account for the Menkes
      neurodegeneration or neurodevelopmental phenotypes. Here, we propose revisions of
      the oligoenzymatic hypothesis that could illuminate the pathogenesis of Menkes
      neurodegeneration and neurodevelopmental defects through unsuspected overlap with
      other neurological conditions including Parkinson's, intellectual disability, and
      schizophrenia.

PMID- 25583189
TI  - Shaken not stirred.

PMID- 25583190
TI  - Pain after breast reconstruction: passive movement or prolonged immobility?

PMID- 25583191
TI  - Tackling the axillary blind spot with PECS II.

PMID- 25583192
TI  - A reply.

PMID- 25583193
TI  - Continuous popliteal sciatic nerve block after day-care foot surgery.

PMID- 25583194
TI  - A reply.

PMID- 25583195
TI  - What is a 'safe blood pressure' for anaesthesia?

PMID- 25583196
TI  - Aseptic precautions for caudal anaesthesia.

PMID- 25583197
TI  - How important is peri-operative hypertension?

PMID- 25583198
TI  - Continuing to use 2% chlorhexidine applicators.

PMID- 25583199
TI  - A reply.

PMID- 25583200
TI  - Safety and efficacy of laryngeal mask airways during tracheostomy.

PMID- 25583201
TI  - NAP5 and consent.

PMID- 25583202
TI  - The expense of unnecessary videolaryngoscopy.

PMID- 25583203
TI  - Ulnar 'dive' may not always identify the median nerve in the forearm.

PMID- 25583204
TI  - Leaking Vygon Cardiff anti-reflux valve.

PMID- 25583205
TI  - Variables not parameters.

PMID- 25583207
TI  - DNA helicases FANCM and DDX11 are determinants of PARP inhibitor sensitivity.
AB  - The encouraging response rates of BRCA1- and BRCA2-mutated cancers toward PARP
      inhibitors make it worthwhile to identify other potential determinants of PARP
      inhibitor responsiveness. Since the Fanconi anemia (FA) pathway coordinates
      several DNA repair pathways, including homologous recombination in which BRCA1
      and BRCA2 play important roles, we investigated whether this pathway harbors
      other predictors of PARP inhibitor sensitivity. Lymphoblastoid cell lines derived
      from individuals with FA or clinically related syndromes, such as Warsaw breakage
      syndrome, were tested for PARP inhibitor sensitivity. Remarkably, we found a
      strong variability in PARP inhibitor sensitivity among different FANCD1/BRCA2
      deficient lymphoblasts, suggesting that PARP inhibitor response depends on the
      type of FANCD1/BRCA2 mutation. We identified the DNA helicases FANCM and DDX11 as
      determinants of PARP inhibitor response. These results may extend the utility of
      PARP inhibition as effective anticancer treatment. 

PMID- 25583208
TI  - Risk factors for urinary catheter associated bloodstream infection.
AB  - OBJECTIVES: Urinary catheter associated bloodstream infection (UCABSI) causes
      significant morbidity, mortality and healthcare costs. We aimed to define the
      risk factors for UCABSI. METHODS: A case-control study was conducted at two
      Australian tertiary hospitals. Patients with urinary source bloodstream infection
      associated with an indwelling urinary catheter (IDC) were compared to controls
      with an IDC who did not develop urinary source bloodstream infection. RESULTS:
      There were 491 controls and 67 cases included in the analysis. Independent
      statistically significant risk factors for the development of UCABSI included
      insertion of the catheter in operating theatre, chronic kidney disease, age
      adjusted Charlson comorbidity index, accurate urinary measurements as reason for
      IDC insertion and dementia. IDCs were inserted for valid reasons in nearly all
      patients, however an appropriate indication at 48 h post-insertion was found in
      only 44% of patients. Initial empiric antibiotics were deemed inappropriate in 23
      patients (34%). CONCLUSION: To our knowledge, this is the first study to look
      specifically at the risk factors for bloodstream infection in urinary
      catheterised patients. Several risk factors were identified. IDC management and
      empiric management of UCABSI could be improved and is likely to result in a
      decreased incidence of infection and its complications.

PMID- 25583209
TI  - Does pharyngeal sampling improve the detection of nasopharyngeal persistent
      carriers of Staphylococcus aureus?

PMID- 25583206
TI  - Chemoradiotherapy and surgery for T4 esophageal cancer in Japan.
AB  - Esophageal cancer is thought to be the most malignant neoplasm due to its
      biological aggressiveness. The most effective treatment modality for esophageal
      cancer, particularly T4 esophageal cancer, is chemoradiotherapy (CRT). Some T4
      patients show long-term survival after receiving CRT, suggesting that even T4
      esophageal cancer can be cured with this modality. Although surgery is performed
      after CRT in some T4 cases, its prognostic benefit is controversial. In this
      paper, we review the status of CRT and conversion surgery as well as the
      development of new regimens and discuss the future prospects of CRT in the
      treatment of T4 esophageal cancer in Japan. 

PMID- 25583210
TI  - Recurrent cellulitis and the role of pentraxin 3 and C-reactive protein.

PMID- 25583211
TI  - Post-glacial population expansion of the Monterey Spanish mackerel Scomberomorus
      concolor in the Gulf of California.
AB  - The level of genetic homogeneity and demographic history of the Monterey Spanish
      mackerel Scomberomorus concolor was assessed by analyses using sequences of the
      mitochondrial (mt)DNA-control region of samples from the two oceanographic
      regions of the Gulf of California in order to define the stock structure for this
      exploited vulnerable species. The data were consistent with a single homogeneous
      population and revealed the hallmark of fluctuations in population size; these
      fluctuations appear to have occurred during glacial events of the middle to late
      Pleistocene, which may in turn be related to the colonization and expansion of S.
      concolor populations in the gulf. 

PMID- 25583212
TI  - Identifying locations of recent TB transmission in rural Uganda: a
      multidisciplinary approach.
AB  - OBJECTIVES: Targeting high Tuberculosis (TB) transmission sites may offer a novel
      approach to TB prevention in sub-Saharan Africa. We sought to characterise TB
      transmission sites in a rural Ugandan township. METHODS: We recruited adults
      starting TB treatment in Tororo, Uganda, over 1 year. Fifty four TB cases
      provided names of frequent contacts, sites of residence, health care, work and
      social activities, and two sputum samples. Mycobacterium tuberculosis (MTB)
      culture-positive specimens underwent spoligotyping to identify strains with
      shared genotypes. We visualised TB case social networks, and obtained, mapped and
      geo-coded global positioning system measures for every location that cases
      reported frequenting 1 month before treatment. Locations of spatial overlap among
      genotype-clustered cases were considered potential transmission sites. RESULTS:
      Six distinct genotypic clusters were identified involving 21 of 33 (64%) MTB
      culture-positive, genotyped cases; none shared a home. Although 18 of 54 (33%) TB
      cases shared social network ties, none of the genotype-clustered cases shared
      social ties. Using spatial analysis, we identified potential sites of within
      cluster TB transmission for five of six genotypic clusters. All sites but one
      were healthcare and social venues, including sites of drinking, worship and
      marketplaces. Cases reported spending the largest proportion of pre-treatment
      person-time (22.4%) at drinking venues. CONCLUSIONS: Using molecular
      epidemiology, geospatial and social network data from adult TB cases identified
      at clinics, we quantified person-time spent at high-risk locations across a rural
      Ugandan community and determined the most likely sites of recent TB transmission
      to be healthcare and social venues. These sites may not have been identified
      using contact investigation alone.

PMID- 25583215
TI  - A method for determining the actual rate of orientation switching of DNA self
      assembled monolayers using optical and electrochemical frequency response
      analysis.
AB  - Electrostatic control of the orientation of fluorophore-labeled DNA strands
      immobilized on an electrode surface has been shown to be an effective
      bioanalytical tool. Modulation techniques and later time-resolved measurements
      were used to evaluate the kinetics of the switching between lying and standing
      DNA conformations. These measurements, however, are the result of a convolution
      between the DNA "switching" response time and the other frequency limited
      responses in the measurement. In this work, a method for analyzing the response
      of a potential driven DNA sensor is presented by calculating the potential
      effectively dropped across the electrode interface (using electrochemical
      impedance spectroscopy) as opposed to the potential applied to the
      electrochemical cell. This effectively deconvolutes the effect of the charging
      time on the observed frequency response. The corrected response shows that DNA is
      able to switch conformation faster than previously reported using modulation
      techniques. This approach will ensure accurate measurements independent of the
      electrochemical system, removing the uncertainty in the analysis of the switching
      response, enabling comparison between samples and measurement systems. 

PMID- 25583214
TI  - Gene introduction into the mitochondria of Arabidopsis thaliana via peptide-based
      carriers.
AB  - Available methods in plant genetic transformation are nuclear and plastid
      transformations because similar procedures have not yet been established for the
      mitochondria. The double membrane and small size of the organelle, in addition to
      its large population in cells, are major obstacles in mitochondrial transfection.
      Here we report the intracellular delivery of exogenous DNA localized to the
      mitochondria of Arabidopsis thaliana using a combination of mitochondria
      targeting peptide and cell-penetrating peptide. Low concentrations of peptides
      were sufficient to deliver DNA into the mitochondria and expression of imported
      DNA reached detectable levels within a short incubation period (12 h). We found
      that electrostatic interaction with the cell membrane is not a critical factor
      for complex internalization, instead, improved intracellular penetration of
      mitochondria-targeted complexes significantly enhanced gene transfer efficiency.
      Our results delineate a simple and effective peptide-based method, as a starting
      point for the development of more sophisticated plant mitochondrial transfection
      strategies. 

PMID- 25583216
TI  - Using DTA and DTAARRAY variables and programming in WinNonlin ASCII models to
      streamline user-defined calculation and data analysis.
AB  - In pharmacokinetic (PK) analysis, there are many occasions where user-defined
      calculations need to be performed before or after the primary PK
      modeling/analysis. Conventionally, these calculations are often executed outside
      of the primary PK analysis by pre- or post-processing data from multiple sources,
      manually entering formulas and multiple additional set-ups. Such analysis
      approaches increase the risk of generating data defects and can employ software
      that is not fully compliant. We propose a method of leveraging DTA and DTAARRAY
      variables plus simple programming techniques in an ASCII model to automate these
      user-defined calculations in WinNonlin and eliminate the need for manual handling
      of data outside of the primary analysis. We demonstrated the application of this
      strategy through three case study examples. In case 1 (post-processing data), DTA
      variables were used to calculate three user-defined parameters in the primary PK
      model. In case 2 (pre-processing data), a baseline correction decision tree was
      programmed into the PK model to account for both the endogenous baseline level as
      well as the presence of residual drug. In case 3, DTAARRAY variables were used to
      perform a looping operation to calculate the difference factor (F1) and the
      similarity factor (F2) in support of in vitro bioequivalence evaluations. 

PMID- 25583217
TI  - Psychiatric consequences of intraoperative awareness: short review and case
      series.
AB  - Intraoperative awareness is an unwanted outcome that consists of an explicit
      recall of events during a surgical procedure performed under general anesthesia.
      Despite its relatively infrequent occurrence, intraoperative awareness is of
      significant concern due to frequent adverse psychiatric sequelae. We present
      three patients who developed posttraumatic sequelae following an episode of
      awareness under anesthesia and discuss the importance of early detection and
      specific care. 

PMID- 25583219
TI  - Outpatient pharmacotherapy and modes of administration for acute repetitive and
      prolonged seizures.
AB  - Acute repetitive seizures (ARS) are a serious epilepsy phenomenon, generally
      described as closely grouped seizures over minutes to 2 days, representing an
      increase in seizure frequency compared with baseline. In some instances, ARS may
      not stop without treatment, and evolution into status epilepticus is a
      significant concern. Additionally, neuronal injury may occur after even brief
      repeated seizures. Given the substantial risks that may be involved with ARS, it
      is crucial to develop appropriate protocols for identification and management of
      this seizure phenomenon. This article focuses on pharmacotherapy and, in
      particular, different modes of administering medication for ARS in the outpatient
      setting. Our aim was to present a review of data from non-randomized and
      randomized, controlled trials to evaluate the efficacy, safety and tolerability
      of out-of-hospital ARS treatments. Several of the studies included patients with
      ARS, as well as patients with prolonged seizures. Prolonged seizures, or seizures
      lasting greater than 5 min, have similar risks and treatment options to those of
      ARS; therefore, this discussion also includes treatment trials and
      recommendations for prolonged seizures. All trials used benzodiazepines, a class
      of drugs that are ideal for the ARS and prolonged seizure populations because of
      their rapid onset of action and minimal adverse effects. Rectal diazepam is
      currently the only formulation approved by the US Food and Drug Administration
      (FDA) for out-of-hospital treatment. Oral benzodiazepines are appropriate only
      for mild ARS. Intramuscular diazepam autoinjection has shown success against ARS
      in clinical trials. Intranasal midazolam and diazepam are in testing. Other
      treatments have also been explored--specifically, buccal midazolam (approved in
      the European Union), sublingual lorazepam and intranasal lorazepam.

PMID- 25583220
TI  - In vivo evaluation of a new 18F-labeled PET ligand, [18F]FEBU, for the imaging of
      I2-imidazoline receptors.
AB  - INTRODUCTION: The functions of I2-imidazoline receptors (I2Rs) are unknown, but
      evidence exists for their involvement in various neuropsychiatric disorders.
      Although a few positron emission tomography (PET) I2R ligands have been
      developed, of which [(11)C]FTIMD and [(11)C]BU99008 were evaluated as PET I2R
      imaging ligands in monkeys, no human PET imaging study using an I2R-selective PET
      ligand has been conducted yet. Thus, we synthesized an (18)F-labeled I2R
      selective ligand (BU99018 or FEBU, Ki for I2Rs=2.6 nM), and evaluated its
      application using rodents in PET imaging in vivo toward the development of a
      clinically-useful I2R PET imaging ligand. METHODS: [(18)F]FEBU was synthesized by
      the reaction of its precursor and [(18)F]fluoroethyl bromide. A biodistribution
      and brain PET study were conducted in mice and rats respectively. RESULTS:
      [(18)F]FEBU was successfully synthesized yielding a radioactivity suitable for
      injection (10.1 +/- 5.3% at the end of the irradiation (n=10) based on (18)F(-)).
      The specific activity at end of synthesis (EOS) was 40-147 TBq/mmol (n=10). The
      radiochemical purity was >99% at EOS and remained >99% for 90 min after EOS. In
      mice brain uptake was relatively high. In the blocking study with the co
      injection of the high-affinity I2R ligand BU224 (1 mg/kg b.w.) brain uptake was
      significantly decreased 30 min post-injection. In the PET studies the
      radioactivity was highly accumulated in the I2R-rich hypothalamus. Pretreatment
      with BU224 (1 mg/kg b.w.) significantly decreased the radioactivity in the
      hypothalamus to 23% of that of the control from 60 to 90 min post-injection.
      CONCLUSION: [(18)F]FEBU was sufficiently stable as a PET ligand and had a
      relatively high specific binding affinity for I2Rs in rats and mice.

PMID- 25583221
TI  - The impact of weakly bound 89Zr on preclinical studies: non-specific accumulation
      in solid tumors and aspergillus infection.
AB  - Preclinical studies involving (89)Zr often report significant bone accumulation,
      which is associated with dissociation of the radiometal from the tracer. However,
      experiments determining the uptake of unbound (89)Zr in disease models are not
      performed as routine controls. The purpose of the present study was to
      investigate the impact of free or weakly bound (89)Zr on PET quantifications in
      disease models, in order to determine if such control experiments are warranted.
      METHODS: Chemical studies were carried out to find a (89)Zr compound that would
      solubilize the (89)Zr as a weak chelate, thus mimicking free or weakly bound
      (89)Zr released in circulation. (89)Zr oxalate had the desired characteristics,
      and was injected into mice bearing FaDu and HT29 solid tumor xenografts, and mice
      infected in the lungs with the mold Aspergillus fumigatus, as well as in healthy
      controls (naive). PET/CT or PET/MR imaging followed to quantify the distribution
      of the radionuclide in the disease models. RESULTS: (89)Zr oxalate was found to
      have a plasma half-life of 5.1 +/- 2.3 h, accumulating mainly in the bones of all
      animals. Both tumor types accumulated (89)Zr on the order of 2-4 %ID/cm(3), which
      is comparable to EPR-mediated accumulation of certain species. In the
      aspergillosis model, the concentration of (89)Zr in lung tissue of the naive
      animals was 6.0 +/- 1.1 %ID/g. This was significantly different from that of the
      animals with advanced disease, showing 11.6 +/- 1.8 %ID/g. CONCLUSIONS: Given the
      high levels of (89)Zr accumulation in the disease sites in the present study, we
      recommend control experiments mapping the biodistribution of free (89)Zr in any
      preclinical study employing (89)Zr where bone uptake is observed. Aqueous (89)Zr
      oxalate appears to be a suitable compound for such studies. This is especially
      relevant in studies where the tracer accumulation is based upon passive
      targeting, such as EPR.

PMID- 25583222
TI  - Cell proliferation and progesterone synthesis depend on lipid metabolism in
      bovine granulosa cells.
AB  - In dairy cows, lipids are essential to support energy supplies for all biological
      functions, especially during early lactation. Lipid metabolism is crucial for
      sustaining proper reproductive function. Alteration of lipid metabolism impacts
      follicular development and affects oocyte developmental competence. Indeed,
      nonesterified fatty acids are able to decrease granulosa cell (GC) proliferation
      and affect estradiol synthesis, thus potentially affecting follicular growth and
      viability. The objective of this study was to assess the impact of lipid
      metabolism on bovine GCs, through the use of the lipid metabolism inhibitors
      etomoxir, an inhibitor of fatty acid (FA) oxidation through inhibition of
      carnitine palmitoyl transferase 1 (CPT1), and C75, an inhibitor of FA synthesis
      through inhibition of fatty acid synthase. We showed that etomoxir and C75
      significantly inhibited DNA synthesis in vitro; C75 also significantly decreased
      progesterone synthesis. Both inhibitors significantly reduced AMPK (5' adenosine
      monophosphate-activated protein kinase) and acetyl-CoA carboxylase
      phosphorylation. Etomoxir also affected the AKT (protein kinase B) signaling
      pathway. Combined, these data suggest that both FA oxidation and synthesis are
      important for the bovine GCs to express a proliferative and steroidogenic
      phenotype and, thus, for sustaining follicular growth. Despite these findings, it
      is important to note that the changes caused by the inhibitors of FA metabolism
      on GCs in vitro are globally mild, suggesting that lipid metabolism is not as
      critical in GCs as was observed in the oocyte-cumulus complex. Further studies
      are needed to investigate the detailed mechanisms by which lipid metabolism
      interacts with GC functions. 

PMID- 25583223
TI  - Embryo cryopreservation and in vitro culture of preimplantation embryos in
      Campbell's hamster (Phodopus campbelli).
AB  - The aims of this study were to compare different protocols of Campbell's hamster
      (Phodopus campbelli) embryos freezing-thawing and to explore the possibilities of
      their in vitro culture. First, the embryos were flushed from the reproductive
      ducts 2 days post coitum at the two-cell stage and cultured in rat one-cell
      embryo culture medium (R1ECM) for 48 hours. Most (86.7%) of the two-cell embryos
      developed to blastocysts in R1ECM. Second, the embryos at the two- to eight-cell
      stages were flushed on the third day post coitum. The eight-cell embryos were
      frozen in 0.25 mL straws according to standard procedures of slow cooling.
      Ethylene glycol (EG) was used either as a single cryoprotectant or in a mixture
      with sucrose. The survival of frozen-thawed embryos was assessed by double
      staining with fluorescein diacetate and propidium iodide. The use of EG as a
      single cryoprotectant resulted in fewer alive embryos when compared with control
      (fresh embryos), but combined use of EG and sucrose improved the survival rate
      after thawing. Furthermore, granulocyte-macrophage colony-stimulating factor rat
      (2 ng/mL) improved the rate of the hamster frozen-thawed embryo development in
      vitro by increasing the final cell number and alleviating nuclear fragmentation.
      Our data show the first attempt in freezing and thawing Campbell's hamster
      embryos and report the possibility of successful in vitro culture for this
      species in R1ECM supplemented with granulocyte-macrophage colony-stimulating
      factor. 

PMID- 25583224
TI  - Biosynthesis and biological functions of terpenoids in plants.
AB  - Terpenoids (isoprenoids) represent the largest and most diverse class of
      chemicals among the myriad compounds produced by plants. Plants employ terpenoid
      metabolites for a variety of basic functions in growth and development but use
      the majority of terpenoids for more specialized chemical interactions and
      protection in the abiotic and biotic environment. Traditionally, plant-based
      terpenoids have been used by humans in the food, pharmaceutical, and chemical
      industries, and more recently have been exploited in the development of biofuel
      products. Genomic resources and emerging tools in synthetic biology facilitate
      the metabolic engineering of high-value terpenoid products in plants and
      microbes. Moreover, the ecological importance of terpenoids has gained increased
      attention to develop strategies for sustainable pest control and abiotic stress
      protection. Together, these efforts require a continuous growth in knowledge of
      the complex metabolic and molecular regulatory networks in terpenoid
      biosynthesis. This chapter gives an overview and highlights recent advances in
      our understanding of the organization, regulation, and diversification of core
      and specialized terpenoid metabolic pathways, and addresses the most important
      functions of volatile and nonvolatile terpenoid specialized metabolites in
      plants.

PMID- 25583225
TI  - Using Hairy Roots for Production of Valuable Plant Secondary Metabolites.
AB  - Plants synthesize a wide variety of natural products, which are traditionally
      termed secondary metabolites and, more recently, coined specialized metabolites.
      While these chemical compounds are employed by plants for interactions with their
      environment, humans have long since explored and exploited plant secondary
      metabolites for medicinal and practical uses. Due to the tissue-specific and low
      abundance accumulation of these metabolites, alternative means of production in
      systems other than intact plants are sought after. To this end, hairy root
      culture presents an excellent platform for producing valuable secondary
      metabolites. This chapter will focus on several major groups of secondary
      metabolites that are manufactured by hairy roots established from different plant
      species. Additionally, the methods for preservations of hairy roots will also be
      reviewed.

PMID- 25583227
TI  - Influence of the COL5A1 rs12722 on musculoskeletal injuries in professional
      soccer players.
AB  - AIM: The aim of this study was to investigate whether COL5A1 rs12722 polymorphism
      is associated with musculoskeletal injuries in elite soccer players. METHODS:
      Fifty-four male professional soccer players of European origin (25.9+/-4.3 years)
      were recruited from a team participating at the Official Italian Professional
      Championship during four consecutive seasons (2009-2013). The incidence and
      severity of musculoskeletal injuries and its relationship to COL5A1 rs12722
      polymorphism were analyzed. DNA was extracted from buccal swab. The cohort was
      genotyped for the COL5A1 rs12722 single nucleotide polymorphism (SNP) through PCR
      and enzyme digestion with BstUI, and musculoskeletal injuries data were collected
      during the four seasons. Injuries were categorized under 5 degrees of severity
      based on the number of days' absence, while musculoskeletal injuries incidence
      was calculated per 1,000 hours of exposure to training and matches ((? injuries/?
      exposure hours) x 1000). RESULTS: No significant differences were found among
      genotypes for incidence of musculoskeletal injuries (P=0.683). Participants with
      TT genotype (3.71+/-0.5, N.=4) showed a trend (P=0.193) versus an higher severity
      of injuries than individuals with TC (2.98+/-0.8, N.=10) or CC (2.75+/-0.95, n=4)
      genotypes. The COL5A1 rs12722 accounted for 44% of severity of injuries
      (P=0.002). CONCLUSION: In conclusion, the COL5A1 rs12722 was found to be
      associated with severity of musculoskeletal injuries but not with incidence of
      musculoskeletal injuries in top-level soccer players.

PMID- 25583228
TI  - Perceptual and cerebro-spinal responses to graded innocuous and noxious stimuli
      following aerobic exercise.
AB  - AIM: The aim of this study was to evaluate the effect of aerobic exercise on
      perceptual and cerebro-spinal responses to graded electrocutaneous stimuli.
      METHODS: The design comprised 2 x 30 min of cycling exercise at 30% and 70% of
      peak oxygen consumption (VO2 peak) on separate occasions in a counter-balanced
      order in 10 healthy participants. Assessment of nociceptive withdrawal reflex
      threshold (NWR-T), pain threshold (PT), and somatosensory evoked potentials
      (SEPs) to graded electrocutaneous stimuli were performed before and after
      exercise. Perceptual magnitude ratings and SEPs were compared at 30%PT, 60%PT,
      100%PT before (Pre), 5 min after (Post1), and 15 min after (Post2) aerobic
      exercise. RESULTS: There was no difference in the NWR-T and the PT following
      exercise at 30% and 70% of VO2 peak. ANOVA for the perceptual response within
      pooled electrocutaneous stimuli show a significant main effect for time
      (F2,18=5.41, P=0.01) but no difference for exercise intensity (F1,9=0.02,
      P=0.88). Within-subject contrasts reveal trend differences between 30%PT and
      100%PT for Pre-Post1 (P=0.09) and Pre-Post2 (P=0.02). ANOVA for the SEPs peak-to
      peak signal amplitude (N1-P1) show significant main effect for time (F2,18=4.04,
      P=0.04) but no difference for exercise intensity (F1,9=1.83, P=0.21). Pairwise
      comparisons for time reveal differences between Pre-Post1 (P=0.06) and Pre-Post2
      (P=0.01). There was a significant interaction for SEPs N1-P1 between exercise
      intensity and stimulus intensity (F2,18=3.56, P=0.05). CONCLUSION: These results
      indicate that aerobic exercise did not increase the electrocutaneous threshold
      for pain and the NWR-T. Aerobic exercise attenuated perceptual responses to
      innocuous stimuli and SEPs N1-P1 response to noxious stimuli.

PMID- 25583229
TI  - Electrocardiographic patterns in African University strength and endurance
      athletes of Zulu descent.
AB  - AIM: There is concern over the effect of training on heart function of athletes
      as recorded by 12-lead electrocardiography (ECG). Although ECG abnormalities with
      respect to ethnic origin of black athletes from the Caribbean, West Africa and
      East Africa have been reported, black athletes from southern Africa, specifically
      participating in different sports, have never been investigated before. The
      purpose of this study was to analyze the ECG patterns in South African students
      of Zulu descent, who represented our university in boxing (endurance modality)
      and body building (resistance modality) at a regional level. METHODS: Fifteen
      subjects each were assigned to an endurance (E), resistance (R) or control (C)
      group, respectively. ECG patterns were recorded with a 12-lead ECG. RESULTS: Our
      subjects indicated no significant differences in ECG patterns in relation to
      whether they participate in strength or endurance related sport. However, 80% of
      the endurance group and 67% of the resistance displayed ECG criteria indicative
      of left ventricular hypertrophy (LVH), group E displays higher R5/S1-wave
      voltages (E=43.3 mm; R=36.8 mm; C=37.1 mm) as well distinctly abnormal ECG
      patterns (E=87%; R=73%; C=53%), raising clinical suspicion of structural heart
      disease. Our cohort presented with non-significant, marked ST-segment elevation
      (53% of both the E and R groups) and inverted T-waves in 27% of the E group.
      CONCLUSION: Similar to findings in other ethnic Africans, a large proportion of
      our Zulu study population displayed ECG criteria indicative of LVH on the
      evidence of a marked increase of R5/S1-wave voltage and ST/T-segment changes with
      no differences in relation to whether they participate in strength or endurance
      related sport.

PMID- 25583230
TI  - Running economy assessment within cardiopulmonary exercise testing for
      recreational runners.
AB  - BACKGROUND: The aim of this study was to evaluate the influence of running
      economy (RE) on running performance within recreational runners of different
      maximal aerobic capacity, and the feasibility of RE assessment within routine
      cardiopulmonary exercise testing (CPET). METHODS: Sixty-eight recreational
      runners (m: 49, f: 19; age: 21-54) completed a graded exercise test (GXT) until
      exhaustion. Maximal oxygen uptake and respiratory compensation point were
      obtained via CPET. RE was calculated as relative oxygen uptake per covered
      distance (mL/kg/km) one step below respiratory compensation point (RCP). Subjects
      were grouped for RE via median split and categorized into one of six fitness
      levels (Very Poor, Poor, Fair, Good, Excellent, Superior) (ACSM 2010). RESULTS:
      Irrespective of fitness levels, recreational runners with a more energy efficient
      movement (RE<215.28 mL/kg/km) reached a significant (P<0.05) higher velocity at
      RCP (12.2 vs. 10.8 km/h). The measured VO2max values ranged between 35.2 and 66.0
      ml/min/kg. Running velocity at RCP of runners within VO2max categories Good and
      Superior differed significantly (P<0.05) between RE groups. CONCLUSIONS: This
      study provides evidence that RE influences submaximal running performance in
      recreational distance runners within a broad range of maximal aerobic capacity.
      Complementing routine CPET with RE assessment at physiological threshold
      intensities and ACSM based categorization seems feasible to delineate the impact
      of movement efficiency and aerobic fitness on performance in recreational
      runners.

PMID- 25583231
TI  - Effects of interset whole-body vibration on bench press resistance training in
      trained and untrained individuals.
AB  - BACKGROUND: Previous studies have demonstrated positive effects of acute
      vibration exercise on concentric strength and power, but few have observed the
      effects of vibration exposure on resistance training. The aim of this study was
      to verify the effects of whole body vibration applied to the chest via hands on
      bench press resistance training in trained and untrained individuals. METHODS:
      Nineteen participants (10 recreationally trained bodybuilders and 9 untrained
      students) performed two randomized sessions of resistance training on separate
      days. Each strength session consisted of 3 bench press sets with a load of 75%
      1RM to failure in each set, with 2 minutes' rest between sets. All subjects
      performed the same strength training with either, vibration exposure (12 Hz, 4
      mm) of 30 seconds immediately before each bench press set or without vibration.
      Number of total repetitions, kinematic parameters, blood lactate and perceived
      exertion were analyzed. RESULTS: In the untrained group, vibration exposure
      caused a significant increase in the mean velocity (from 0.36+/-0.02 to 0.39+/
      0.03 m/s) and acceleration (from 0.75+/-0.10 to 0.86+/-0.09 m/s2), as well as a
      decrease in perceived effort (from 8+/-0.57 to 7.35+/-0.47) in the first bench
      press set, but no change was observed in the third bench press set. In the
      recreationally trained bodybuilders, vibration exposure did not cause any
      improvement on the performance of bench press resistance training. CONCLUSIONS:
      These results suggest that vibration exposure applied just before the bench press
      exercise could be a good practice to be implemented by untrained individuals in
      resistance training.

PMID- 25583232
TI  - Influence of baseline heart rate variability on repeated sprint performance in
      young soccer players.
AB  - BACKGROUND: The aim of this study was to assess the influence of the autonomic
      system on the performance of repeated sprints, involving predominantly
      neuromuscular power, in young soccer players. METHODS: Twelve young soccer
      players, selected for the Sicilian Regional Football Representative, mean age 15
      years, were recruited. Baseline heart rate variability (HRV) was measured and
      indices of power spectral analysis (LF, HF, and LF/HF ratio) were calculated to
      evaluate the sympathovagal balance. The athletes performed 10 maximal 6-second
      cycling sprints (RS), interspersed with 30 seconds of recovery, to measure the
      peak power output (PP) represented by the highest power value recorded during a 6
      second sprint, and the mean peak power output (MPP) represented by the average of
      all highest power values recorded within a repeated-sprint bout. RESULTS: PP was
      negatively correlated with LF (rho=-0.685, P=0.0141) and LF/HF (rho=-0.709,
      P=0.0098), and positively correlated with HF (rho=0.684, P=0.0142). MPP was
      negatively correlated with LF (rho=-0.610, P=0.0350) and LF/HF (rho=-0.606,
      P=0.0366), and positively correlated with HF (rho=0.731, P=0.0070). CONCLUSIONS:
      Our study shows that a baseline parasympathetic predominance in the autonomic
      nervous system balance is associated with a better neuromuscular contribution to
      performance, resulting in higher values of PP and MPP during brief repeated
      maximal cycling sprints. The assessment of baseline HRV before exercise may be
      useful for to monitor the physical condition of young soccer players and their
      readiness status to a higher performance.

PMID- 25583234
TI  - Prognostic factors for the recurrence of myxoid liposarcoma: 20 cases with up to
      8 years follow-up.
AB  - INTRODUCTION: Myxoid liposarcomas (MLS) are the second most common type of
      liposarcoma. Although some MRI findings are distinctively characteristics of MLS,
      the diagnosis can be tricky in tumors with a large portion of round cells (RC).
      Known predictors of an unfavorable outcome include age, tumor size, high RC
      content and positive resection margins. The goal of this retrospective study was
      to define prognostic factors for recurrence, with special emphasis on the
      percentage of RCs and medical care provided in a non-specialized center. PATIENTS
      AND METHODS: Twenty patients (11 women, 9 men) with a mean age of 44.3 years (18
      73) were reviewed after a mean of 55.9 months. Six of these patients had been
      operated at a non-specialized center. The diagnostic MRI was read by a
      specialized radiologist and the resection procedures performed by two specialized
      surgeons. Tumors were labeled as either "pure myxoid liposarcoma" or
      "myxoid/round-cell liposarcoma". The local recurrence-free survival rate and
      mortality rate were calculated. RESULTS: Fifteen patients had undergone an MRI
      during the initial assessment. The typical MRI findings of MLS were present in
      four of them. The MRI suggested a non-specific lesion in the other 11 patients.
      After correlation with pathology findings, these tumors contained more than 5%
      round cells. The fourteen patients treated at our facility had undergone a
      biopsy, while none of the ones treated outside did. Five patients had R0
      resection margins and 15 had R1 margins. Prognostic factors for recurrence
      consisted of age, tumor size >10 cm, R1 resection margins, FNCLCC grade 2+R1
      margins, medical care at a non-specialized center, and >5% round cells. There
      were eight local recurrences and three metastases (15%). Two patients died (90%
      overall survival rate). DISCUSSION: The risk of local recurrence was 3.86 times
      greater in this study when the tumor contained more than 5% RCs, which is
      consistent with published data. The MLS diagnosis was made only four times based
      on the initial MRI because misleading nature of high RC tumors. R1 resection
      margins are a risk factor for local recurrence. However, cases with R1 margins
      have a recurrence rate that is similar to R0 cases when the surgery is performed
      at a specialized cancer center. Treatment of MLS in a non-specialized center is a
      key negative prognostic factor. The reported rate of metastasis varies. Atypical
      extrapulmonary localizations are common, and often multifocal. MRI has been shown
      to be superior at detecting secondary lesions and some have suggested that a full
      body MRI should be performed. CONCLUSION: Prognostic factors for the recurrence
      of myxoid liposarcomas have been identified. MRI analysis is not definitive and
      must be supplemented by a biopsy.

PMID- 25583233
TI  - Structural importance of the C-terminal region in pig aldo-keto reductase family
      1 member C1 and their effects on enzymatic activity.
AB  - BACKGROUND: Pig aldo-keto reductase family 1 member C1 (AKR1C1) belongs to AKR
      superfamily which catalyzes the NAD(P)H-dependent reduction of various substrates
      including steroid hormones. Previously we have reported two paralogous pig
      AKR1C1s, wild-type AKR1C1 (C-type) and C-terminal-truncated AKR1C1 (T-type).
      Also, the C-terminal region significantly contributes to the NADPH-dependent
      reductase activity for 5alpha-DHT reduction. Molecular modeling studies combined
      with kinetic experiments were performed to investigate structural and enzymatic
      differences between wild-type AKR1C1 C-type and T-type. RESULTS: The results of
      the enzyme kinetics revealed that Vmax and kcat values of the T-type were 2.9 and
      1.6 folds higher than those of the C-type. Moreover, catalytic efficiency was
      also 1.9 fold higher in T-type compared to C-type. Since x-ray crystal structures
      of pig AKR1C1 were not available, three dimensional structures of the both types
      of the protein were predicted using homology modeling methodology and they were
      used for molecular dynamics simulations. The structural comparisons between C
      type and T-type showed that 5alpha-DHT formed strong hydrogen bonds with
      catalytic residues such as Tyr55 and His117 in T-type. In particular, C3 ketone
      group of the substrate was close to Tyr55 and NADPH in T-type. CONCLUSIONS: Our
      results showed that 5alpha-DHT binding in T-type was more favorable for catalytic
      reaction to facilitate hydride transfer from the cofactor, and were consistent
      with experimental results. We believe that our study provides valuable
      information to understand important role of C-terminal region that affects
      enzymatic properties for 5alpha-DHT, and further molecular mechanism for the
      enzyme kinetics of AKR1C1 proteins.

PMID- 25583235
TI  - Survey of French spine surgeons reveals significant variability in spine trauma
      practices in 2013.
AB  - BACKGROUND: In France, attempts to define common ground during spine surgery
      meetings have revealed significant variability in clinical practices across
      different schools of surgery and the two specialities involved in spine surgery,
      namely, neurosurgery and orthopaedic surgery. OBJECTIVES: To objectively
      characterise this variability by performing a survey based on a fictitious spine
      trauma case. Our working hypothesis was that significant variability existed in
      trauma practices and that this variability was related to a lack of strong
      scientific evidence in spine trauma care. METHODS: We performed a cross-sectional
      survey based on a clinical vignette describing a 31-year-old male with an L1
      burst fracture and neurologic symptoms (numbness). Surgeons received the vignette
      and a 14-item questionnaire on the management of this patient. For each question,
      surgeons had to choose among five possible answers. Differences in answers across
      surgeons were assessed using the Index of Qualitative Variability (IQV), in which
      0 indicates no variability and 1 maximal variability. Surgeons also received a
      questionnaire about their demographics and surgical experience. RESULTS: Of 405
      invited spine surgeons, 200 responded to the survey. Five questions had an IQV
      greater than 0.9, seven an IQV between 0.5 and 0.9, and two an IQV lower than
      0.5. Variability was greatest about the need for MRI (IQV=0.93), degree of
      urgency (IQV=0.93), need for fusion (IQV=0.92), need for post-operative bracing
      (IQV=0.91), and routine removal of instrumentation (IQV=0.94). Variability was
      lowest for questions about the need for surgery (IQV=0.42) and use of the
      posterior approach (IQV=0.36). Answers were influenced by surgeon specialty, age,
      experience level, and type of centre. CONCLUSION: Clinical practice regarding
      spine trauma varies widely in France. Little published evidence is available on
      which to base recommendations that would diminish this variability.

PMID- 25583236
TI  - Post-traumatic knee stiffness: surgical techniques.
AB  - Post-traumatic knee stiffness and loss of range of motion is a common
      complication of injuries to the knee area. The causes of post-traumatic knee
      stiffness can be divided into flexion contractures, extension contractures, and
      combined contractures. Post-traumatic stiffness can be due to the presence of
      dense intra-articular adhesions and/or fibrotic transformation of peri-articular
      structures. Various open and arthroscopic surgical treatments are possible. A
      precise diagnosis and understanding of the pathology is mandatory prior to any
      surgical treatment. Failure is imminent if all pathologies are not addressed
      correctly. From a general point of view, a flexion contracture is due to
      posterior adhesions and/or anterior impingement. On the other hand, extension
      contractures are due to anterior adhesions and/or posterior impingement. This
      overview will describe the different modern surgical techniques for treating post
      traumatic knee stiffness. Any bony impingements must be treated before soft
      tissue release is performed. Intra-articular stiff knees with a loss of flexion
      can be treated by an anterior arthroscopic arthrolysis. Extra-articular pathology
      causing a flexion contracture can be treated by open or endoscopic quadriceps
      release. Extension contractures can be treated by arthroscopic or open posterior
      arthrolysis. Postoperative care (analgesia, rehabilitation) is essential to
      maintaining the range of motion obtained intra-operatively. 

PMID- 25583226
TI  - Pan-African phylogeography of a model organism, the African clawed frog 'Xenopus
      laevis'.
AB  - The African clawed frog Xenopus laevis has a large native distribution over much
      of sub-Saharan Africa and is a model organism for research, a proposed disease
      vector, and an invasive species. Despite its prominent role in research and
      abundance in nature, surprisingly little is known about the phylogeography and
      evolutionary history of this group. Here, we report an analysis of molecular
      variation of this clade based on 17 loci (one mitochondrial, 16 nuclear) in up to
      159 individuals sampled throughout its native distribution. Phylogenetic
      relationships among mitochondrial DNA haplotypes were incongruent with those
      among alleles of the putatively female-specific sex-determining gene DM-W, in
      contrast to the expectation of strict matrilineal inheritance of both loci.
      Population structure and evolutionarily diverged lineages were evidenced by
      analyses of molecular variation in these data. These results further
      contextualize the chronology, and evolutionary relationships within this group,
      support the recognition of X. laevis sensu stricto, X. petersii, X. victorianus
      and herein revalidated X. poweri as separate species. We also propose that
      portions of the currently recognized distributions of X. laevis (north of the
      Congo Basin) and X. petersii (south of the Congo Basin) be reassigned to X.
      poweri. 

PMID- 25583239
TI  - Important information about clinical practice guidelines: key tools for improving
      quality of care and patient outcomes.

PMID- 25583237
TI  - Does the PFNATM nail limit impaction in unstable intertrochanteric femoral
      fracture? A 115 case-control series.
AB  - INTRODUCTION: Femoral neck shortening after dynamic fixation of extra-capsular
      fracture may impair functional results, but is rarely assessed. The present study
      measured impaction in stable and unstable fractures (on the Ender classification)
      treated by PFNATM nail. The objectives were: 1) to validate the Ender
      classification to assess fracture stability; 2) to determine whether neck
      shortening and head purchase quality varied with stability; and 3) to determine
      the functional impact of femoral neck shortening. HYPOTHESIS: The study
      hypothesis was that the PFNATM nail stabilizes unstable as well as stable
      fractures. MATERIALS AND METHODS: One hundred and fifteen consecutive patients,
      aged over 70 years, operated on for intertrochanteric fracture using the PFNATM
      nail were followed up prospectively for 6 months. Multivariate analysis,
      including age, gender, assembly quality and body-mass index, was applied to
      assess the predictive power of the Ender classification with respect to femoral
      neck shortening. Secondly, patients were grouped according to stable versus
      unstable fracture (n=70 and 45, respectively), and impaction and femoral head
      purchase were assessed on a dedicated radiographic protocol. Functional results
      were assessed on Parker score. RESULTS: In the unstable fracture group, 3
      assembly failures required revision by total hip replacement. Ender grade>2 was
      significantly predictive of>5mm neck shortening. Neck shortening was greater in
      unstable fracture: 8.1 +/- 8.4mm (range, 4-32 mm), versus 2.5 +/- 3.7 mm (range,
      3-14 mm) (P=0.0004). Mean blade cut-through was 1.2 +/- 2.9 mm (range, 1-12 mm)
      in unstable fracture, versus 0.3 +/- 1.3 mm (range, 1-6mm) (P=0.02). Mean cut-out
      was 2.3 +/- 6 mm (range, 2-21 mm) in unstable fracture, versus 0.5 +/- 2.6 mm
      (range, 1-8mm) (P=0.03). Parker scores diminished comparably in the two groups,
      without significant difference at follow-up: 3.9 +/- 2.6 (range, 0-9) in stable
      and 3.1 +/- 1.9 (range, 0-8) in unstable fracture; reduction in Parker score
      showed no correlation with femoral neck shortening (r=0.013, P=0.88). DISCUSSION:
      The PFNATM nail provides poorer stabilization of unstable compared to stable
      fracture. Femoral neck shortening should be taken into account in assessing
      internal fixation hardware perfomances. LEVEL OF EVIDENCE: Level III. Prospective
      case-control study.

PMID- 25583240
TI  - Chemical composition and antibacterial activity of methanolic extract and
      essential oil of Iranian Teucrium polium against some of phytobacteria.
AB  - The antibacterial activity of essential oil and methanolic extract of Teucrium
      polium was determined against Pseudomonas aeruginosa, Pantoea agglomerans,
      Brenneria nigrifluens, Rhizobium radiobacter, Rhizobium vitis, Streptomyces
      scabies, Ralstonia solanacearum, Xanthomonas campestris and Pectobacterium
      cartovorum by disc diffusion method. Minimum inhibitory concentration and minimum
      bactericidal concentration were determined by using the serial dilution method.
      Chemical composition of essential oil and methanolic extract was determined by GC
      MS and HPLC. alpha-Pinene (25.769%) and myrcene (12.507) were of the highest
      percentage in T. polium essential oil, and sinapic acid (15.553 mg/g) and eugenol
      (6.805 mg/g) were the major compounds in the methanolic extract. Our results
      indicate that both methanolic extract and essential oil did not show
      antibacterial activity against P. aeruginosa. Also the essential oil did not show
      antibacterial activity against P. cartovorum. In general, both methanolic extract
      and essential oil showed the same antibacterial activity against R. solanacearum,
      P. agglomerans, B. nigrifluens and S. scabies. 

PMID- 25583241
TI  - The accurate estimation of physicochemical properties of ternary mixtures
      containing ionic liquids via artificial neural networks.
AB  - The estimation of the density and refractive index of ternary mixtures comprising
      the ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate, 2-propanol,
      and water at a fixed temperature of 298.15 K has been attempted through
      artificial neural networks. The obtained results indicate that the selection of
      this mathematical approach was a well-suited option. The mean prediction errors
      obtained, after simulating with a dataset never involved in the training process
      of the model, were 0.050% and 0.227% for refractive index and density estimation,
      respectively. These accurate results, which have been attained only using the
      composition of the dissolutions (mass fractions), imply that, most likely,
      ternary mixtures similar to the one analyzed, can be easily evaluated utilizing
      this algorithmic tool. In addition, different chemical processes involving ILs
      can be monitored precisely, and furthermore, the purity of the compounds in the
      studied mixtures can be indirectly assessed thanks to the high accuracy of the
      model. 

PMID- 25583238
TI  - Sparse expression bases in cancer reveal tumor drivers.
AB  - We define a new category of candidate tumor drivers in cancer genome evolution:
      'selected expression regulators' (SERs)-genes driving dysregulated
      transcriptional programs in cancer evolution. The SERs are identified from genome
      wide tumor expression data with a novel method, namely SPARROW ( SPAR: se
      selected exp R: essi O: n regulators identified W: ith penalized regression).
      SPARROW uncovers a previously unknown connection between cancer expression
      variation and driver events, by using a novel sparse regression technique. Our
      results indicate that SPARROW is a powerful complementary approach to identify
      candidate genes containing driver events that are hard to detect from sequence
      data, due to a large number of passenger mutations and lack of comprehensive
      sequence information from a sufficiently large number of samples. SERs identified
      by SPARROW reveal known driver mutations in multiple human cancers, along with
      known cancer-associated processes and survival-associated genes, better than
      popular methods for inferring gene expression networks. We demonstrate that when
      applied to acute myeloid leukemia expression data, SPARROW identifies an
      apoptotic biomarker (PYCARD) for an investigational drug obatoclax. The PYCARD
      and obatoclax association is validated in 30 AML patient samples. 

PMID- 25583242
TI  - Heavy metal pollution assessment in relation to sediment properties in the
      coastal sediments of the southern Caspian Sea.
AB  - This study aimed to evaluate major elements and heavy metal concentrations of
      Arsenic (As), Copper (Cu), Chromium (Cr), Cobalt (Co), Vanadium (V), Nickel (Ni),
      lead (Pb) and Zinc (Zn) in surface sediments of the southern Caspian Sea. Metal
      contents in the sediment were observed in the order of: V>Cr>Zn>Ni>Co>Cu>Pb>As.
      Correlations between elements showed that sediment TOM, grain size and chemical
      composition are the main factors that influence the distribution of heavy metals.
      According to the pollution load index (PLI), sediments from some sampling sites
      were polluted. Concentrations of Ni, As, Cr and Cu were higher than sediment
      quality guidelines at some sampling sites, implying potential adverse impacts of
      these metals. 

PMID- 25583243
TI  - [Profile and prognosis of patients over 85 years old with anemia living in the
      community. Octabaix Study].
AB  - OBJECTIVES: To analyze the prevalence of anemia in a sample of patients over 85
      years old. To explore possible differentiating features in the groups of people
      with and without anemia, and to evaluate the relationship of anemia with
      mortality after a follow-up of 3 years. MATERIAL AND METHODS: An observational
      multicenter study was conducted on a cohort of people born in 1924 and who lived
      in the community. Socio-demographic variables, comorbidity, functionality,
      cognitive status, social risk, perceived quality of life, nutritional status,
      drug consumption and laboratory parameters were collected. Multivariate logistic
      regression analysis was performed. RESULTS: A total of 328 inhabitants were
      included, of whom 61.6% were women. The prevalence of anemia was 24%.
      Statistically significant differences in the Charlson index were found, showing
      higher values in anemic patients (P=0001) and in the Barthel index (BI) and in
      the Lawton index (LI), with lower levels in anemic patients (P=002 for both).
      Patients with anemia had a poorer perception of their quality of life (P=015).
      The presence of anemia was associated with more dependence according the BI
      values (OR 0.985; 95% CI: 0973-0997) and with higher comorbidity according the
      Charlson index (OR 1.314; 95% CI: 1124-1536). Mortality was higher in the group
      of patients with anemia, reaching statistically significant differences in the
      third year P=005). CONCLUSIONS: In our cohort anemia is a fairly prevalent
      feature in the population over 85 years old, and is associated with higher
      mortality at three years of follow up. Patients with anemia had worse physical
      functioning and greater comorbidity.

PMID- 25583244
TI  - Insulin resistance as a predictor of early virologic response to HCV therapy
      among chronic HCV Egyptian patients.
AB  - Prior assessment of insulin resistance by HOMA-IR is emerging as an important
      milestone in the treatment of patients with chronic hepatitis C. This cost
      effective tool is recommended to individualize treatment duration, or to exclude
      those with low insulin sensitivity from being treated until ameliorating their
      state of insulin resistance (IR). The present work aims to elucidate further the
      effect IR state on early viral kinetic response to Chronic hepatitis C virus
      (HCV) therapy and the impact of HCV treatment and viral eradication on insulin
      sensitivity. Insulin sensitivity was assessed using the HOMA-IR method. All
      enrolled patients were treated with a dual therapy (pegylated interferon-alpha
      plus ribavirin) for 48 weeks and evaluated using qRT-PCR for early virologic
      response as well as the impact of treatment on insulin sensitivity throughout the
      early period of therapy. Of a total 392 chronic HCV cases, early virologic
      response was achieved by 318 (81.1%). IR was detected in 241 (61.5%) chronic HCV
      patient of which 73.4% responded to treatment. Early virologic response among
      patients with > 2.18 HOMA-IR value were significantly lower than those with HOMA
      IR values <=2.18 (P < 0.0001). IR was significantly associated with high baseline
      BMI. Steatosis and fibrosis correlated with IR but neither independently
      predicted early virologic response. Pretreatment IR < 2.18, low fasting blood
      glucose, low and intermediate HCV viral load, normal BMI, and non-smoking were
      independent factors associated with early virologic response. IR interferes with
      early virologic response to the antiviral care. Clinical application of
      pretreatment HOMA-IR assessment could help in predicting early treatment outcome
      and thus enable treatment regimens to be optimized and individually tailored.

PMID- 25583245
TI  - The association of lifetime insight and cognition in psychosis.
AB  - Poor insight has been related to poor course in psychosis. However, the role of
      cognition in insight remains unclear. The aim of this study was to examine the
      influence of cognition and lifetime psychopathological dimensions on insight in
      psychosis. We followed up 42 patients with psychotic disorders over 10years.
      Lifetime psychopathological dimensions and cognitive performance were assessed.
      Patients were divided into two groups by lifetime patterns of insight and
      compared with 42 healthy volunteers. Lower IQ and poorer social cognition were
      associated with higher risks of poorer lifetime insight of feeling ill and global
      insight respectively. Lifetime negative symptoms were associated with a higher
      risk of poorer lifetime insight into symptoms. Lifetime lack of insight is
      independent of cognitive impairment in specific domains, except for social
      cognition. Higher IQ may contribute to better lifetime awareness of illness,
      while better ability to manage emotions is involved in lifetime global insight. 

PMID- 25583247
TI  - Plasma oxytocin levels predict olfactory identification and negative symptoms in
      individuals with schizophrenia.
AB  - Basic neuroscience research provides strong evidence for the role of oxytocin in
      olfactory processes and social affiliation in rodents. Given prior indication of
      olfactory impairments that are linked to greater severity of asociality in
      schizophrenia, we examined the association between plasma oxytocin levels and
      measures of olfaction and social outcome in a sample of outpatients with
      schizophrenia (n=39) and demographically matched healthy controls (n=21).
      Participants completed the 40-item University of Pennsylvania Smell
      Identification Test (UPSIT), and rated each odor for how positive and how
      negative it made them feel. Results indicated that individuals with schizophrenia
      had higher plasma oxytocin levels and lower overall accuracy for UPSIT items than
      controls. Individuals with schizophrenia also reported experiencing more negative
      emotionality than controls in response to the olfactory stimuli. Lower plasma
      oxytocin levels were associated with poorer accuracy for pleasant and unpleasant
      odors and greater severity of asociality in individuals with schizophrenia. These
      findings suggest that endogenous oxytocin levels may be an important predictor of
      olfactory identification deficits and negative symptoms in schizophrenia. 

PMID- 25583248
TI  - Predictors of neuropsychological effort test performance in schizophrenia.
AB  - There is some evidence that insufficient effort may be common in schizophrenia,
      posing significant threats to the validity of neuropsychological test results.
      Low effort may account for a significant proportion of variance in
      neuropsychological test scores and the generalized cognitive deficit that
      characterizes the disorder. The current study evaluated clinical predictors of
      insufficient effort in schizophrenia using an embedded effort measure, the
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Effort
      Index (EI). Participants were 330 patients meeting DSM-IV-TR criteria for
      schizophrenia, schizoaffective disorder, or another psychotic disorder who
      received a battery of neuropsychological tests, including: Wechsler Test of Adult
      Reading (WTAR), Wechsler Abbreviated Scale of Intelligence (WASI), and RBANS.
      Clinical assessments designed to measure functional outcome and symptoms were
      also obtained. Results indicated that 9.4% of patients failed the EI. Patients
      who failed had lower full-scale, verbal, and performance IQ, as well as poorer
      performance on RBANS domains not included in the EI (immediate memory, language,
      and visuospatial/construction). Patients who failed the EI also displayed poorer
      community-based vocational outcome, greater likelihood of having "deficit
      schizophrenia" (i.e., primary and enduring negative symptoms), and increased
      severity of positive symptoms. Regression analyses revealed that insufficient
      effort was most significantly predicted by a combination of low IQ, negative
      symptoms, and positive symptoms. Findings suggest that although insufficient
      effort may be relatively uncommon in schizophrenia, it is associated with
      important clinical outcomes. The RBANS EI may be a useful tool in evaluating
      insufficient effort in schizophrenia. 

PMID- 25583250
TI  - Cystic trichoblastoma: a report of two cases with an immunohistochemical study.
AB  - We herein report two cases of cystic trichoblastoma with an immunohistochemical
      study. The histopathological findings in these cases included new information,
      namely, their being composed of two and three cysts, the cystic components had
      features of a steatocystoma and a hybrid cyst in one case, and there were
      projections of an aggregation of trichoblastoma, as well as papillary projections
      of follicular germinative cells, from the cyst walls. The follicular germinative
      cells observed in the papillary projections and in the aggregations of
      trichoblastoma expressed cytokeratin-15 (clone C8/144B) and PHLDA1, markers of
      follicular stem cells. Cystic trichoblastoma is a unique type of trichoblastoma,
      which originates from the cyst walls of an infundibular cyst (usually) or
      steatocystoma/hybrid cyst (rarely). In some cases, a trichoblastic infundibular
      cyst is considered to be a minor form (or possibly a primitive stage) of cystic
      trichoblastoma. 

PMID- 25583251
TI  - Current management of asymptomatic carotid stenosis.
AB  - Asymptomatic carotid stenosis (ACS) is a common problem in daily clinical
      practice, and its management is still the subject of controversy. In contrast to
      symptomatic carotid disease, the main studies on surgical treatment of patients
      with ACS have shown only a modest benefit in the primary prevention of stroke. In
      addition, current medical treatment has drastically decreased the risk of stroke
      in patients with ACS. Selecting patients amenable to endovascular treatment and
      determining how and when to conduct the ultrasound follow-up of these patients
      are issues that still need resolving. This article analyzes two new studies
      underway that provide evidence for better management of ACS in daily clinical
      practice. 

PMID- 25583249
TI  - Preliminary evidence for reduced auditory lateral suppression in schizophrenia.
AB  - BACKGROUND: Well-documented auditory processing deficits such as impaired
      frequency discrimination and reduced suppression of auditory brain responses in
      schizophrenia (SZ) may contribute to abnormal auditory functioning in everyday
      life. Lateral suppression of non-stimulated neurons by stimulated neurons has not
      been extensively assessed in SZ and likely plays an important role in precise
      encoding of sounds. Therefore, this study evaluated whether lateral suppression
      of activity in auditory cortex is impaired in SZ. METHODS: SZ participants and
      control participants watched a silent movie with subtitles while listening to
      trials composed of a 0.5s control stimulus (CS), a 3s filtered masking noise
      (FN), and a 0.5s test stimulus (TS). The CS and TS were identical on each trial
      and had energy corresponding to the high energy (recurrent suppression) or low
      energy (lateral suppression) portions of the FN. Event-related potentials were
      recorded and suppression was measured as the amplitude change between CS and TS.
      RESULTS: Peak amplitudes of the auditory P2 component (160-260ms) showed reduced
      lateral but not recurrent suppression in SZ participants. CONCLUSIONS: Reduced
      lateral suppression in SZ participants may lead to overlap of neuronal
      populations representing different auditory stimuli. Such imprecise neural
      representations may contribute to the difficulties SZ participants have in
      discriminating complex stimuli in everyday life.

PMID- 25583252
TI  - Teaching of clinical ultrasonography to undergraduates: students as mentors.
AB  - BACKGROUND: Ultrasonography is a highly useful diagnostic technique that
      supplements traditional physical examinations. OBJECTIVE: To demonstrate that
      students previously trained in clinical ultrasonography are capable of
      instructing other students in a similar manner in a short period of time ("peer
      mentoring"). METHODOLOGY: Five medical students in their 5th year, trained in
      abdominal and cardiac ultrasonography by physicians with experience, instructed
      24 other students in the same procedure. The training consisted of an online
      theoretical course and practical training lasting about 12hours, in which each
      student had to perform 6 basic abdominal planes and 4 basic cardiac planes on 20
      healthy volunteers. Subsequently, the students underwent an objective assessment
      test on healthy models performed by expert physicians in clinical
      ultrasonography. RESULTS: The students managed to correctly identify 90.2% of the
      basic abdominal planes, except for the left coronal (spleen and left kidney) and
      subcostal (gallbladder) planes, with slightly lower success rates of 82.5% and
      80%, respectively. Due to the greater difficulty of obtaining cardiac planes, the
      success rate was lower: 70.3%, in the subxiphoid, short parasternal and four
      chamber planes. The cardiac plane with the fewest errors in identification was
      the parasternal long plane (90% success). We observed no statistically
      significant differences between the results (teaching capacity) of the various
      mentors. CONCLUSION: Medical students are capable of instructing other colleagues
      (peer mentoring) on the basic aspects of abdominal and cardiac ultrasonography
      after a relatively short training period.

PMID- 25583246
TI  - The impact of NMDA receptor hypofunction on GABAergic neurons in the
      pathophysiology of schizophrenia.
AB  - While the dopamine hypothesis has dominated schizophrenia research for several
      decades, more recent studies have highlighted the role of fast synaptic
      transmitters and their receptors in schizophrenia etiology. Here we review
      evidence that schizophrenia is associated with a reduction in N-methyl-d
      aspartate receptor (NMDAR) function. By highlighting postmortem, neuroimaging and
      electrophysiological studies, we provide evidence for preferential disruption of
      GABAergic circuits in the context of NMDAR hypo-activity states. The functional
      relationship between NMDARs and GABAergic neurons is realized at the molecular,
      cellular, microcircuit and systems levels. A synthesis of findings across these
      levels explains how NMDA-mediated inhibitory dysfunction may lead to aberrant
      interactions among brain regions, accounting for key clinical features of
      schizophrenia. This synthesis of schizophrenia unifies observations from diverse
      fields and may help chart pathways for developing novel diagnostics and
      therapeutics. 

PMID- 25583254
TI  - Caught! Crystal trapping of a side-on peroxo bound to Cr(iv).
AB  - A Cr(iv)eta(2)-peroxo complex crystallizes from 33% aqueous H2O2. The complex is
      a likely intermediate in catalytic disproportionation of H2O2 proposed to occur
      through a single metal site mechanism in solution - and solid state. 

PMID- 25583253
TI  - Rare anaphylaxis and functioning adrenal adenoma.

PMID- 25583255
TI  - Stereoselective synthesis of rapamycin fragment to build a macrocyclic toolbox.
AB  - A stereoselective synthesis of a rapamycin fragment is developed and further
      utilized toward building a macrocyclic chemical toolbox. The amino alcohol moiety
      embedded in the 22-membered macrocyclic ring allowed for the addition of a
      variation in the chiral side chain. The key reactions leading to the synthesis of
      the rapamycin-derived pyran fragment include the following: (i) Paterson aldol,
      (ii) stereoselective beta-OH carbonyl reduction, and (iii) regio- and
      stereoselective intramolecular oxy-Michael reaction. The other piece needed for
      building the macrocyclic diversity was obtained from the coupling of various
      amino alcohol moieties with S-pipecolic acid. 

PMID- 25583256
TI  - Effect of C1-Esterase-inhibitor in angiotensin-converting enzyme inhibitor
      induced angioedema.
AB  - OBJECTIVES/HYPOTHESIS: The study objective was to generate pilot data to evaluate
      the effectiveness and safety of C1-esterase-inhibitor concentrate (C1-INH)
      compared to standard treatment in patients with angiotensin-converting enzyme
      inhibitor (ACEi)-induced angioedema affecting the upper aerodigestive tract.
      STUDY DESIGN: Proof-of-concept case series with historical control. METHODS:
      Adult patients with angioedema in the upper aerodigestive tract presenting to the
      emergency department were included. After establishing the diagnosis of ACEi
      induced angioedema based on patient history and thorough clinical examination,
      all patients were administered 1,000 international units (IU) of C1-INH
      intravenously. A historical control group consisting of adult patients with ACEi
      induced angioedema who had been treated with intravenous corticosteroids and
      antihistamines at the same institution over the past 8 years was used for
      comparison. The most important parameters assessed were the time to complete
      resolution of symptoms and the need for intubation or tracheotomy. RESULTS: Ten
      patients were included in the C1-INH group and 47 in the
      corticosteroid/antihistamine group. The time to complete resolution of symptoms
      was considerably longer in the historical control group (33.1 +/- 19.4 hours)
      than in the C1-INH group (10.1 +/- 3.0 hours). No intubation or tracheotomy was
      needed in the C1-INH group (0/10 patients), whereas three out of the 47
      historical controls required tracheotomy and two were intubated (5/47).
      CONCLUSION: The results suggest a role for C1-INH as an effective and safe
      therapeutic option in patients with ACEi-induced angioedema, which needs to be
      confirmed by further larger and double-blinded studies. LEVEL OF EVIDENCE: 4.

PMID- 25583258
TI  - High-risk HPV testing in the management of atypical glandular cells: A systematic
      review and meta-analysis.
AB  - Whereas the utility of high-risk HPV (hrHPV) testing is widely accepted in triage
      of women with atypical squamous lesions, its role in managing atypical glandular
      cells (AGC) is not fully elucidated. A systematic review and meta-analysis were
      performed to evaluate the accuracy of hrHPV testing in the management of women
      with AGC to detect underlying high-grade intraepithelial neoplasia or worse, and
      adenocarcinoma in situ or worse (AIS+). Additionally, the diagnosis of extra
      cervical cancer was considered as an outcome in this review. A bibliographic
      database search (PubMed, EMBASE, CENTRAL) identified twelve eligible studies. The
      occurrence of cervical intraepithelial neoplasia grade two or worse including
      AIS+ (CIN2+/AIS+), was 19.8% among women with AGC, and 55.7% among women with AGC
      and concurrent squamous lesions (atypical squamous cells of undetermined
      significance or worse, ASC-US+). The pooled sensitivity and specificity of hrHPV
      testing with Hybrid Capture 2 (HC2) to detect CIN2+/AIS+ in women with AGC was
      90.0% (95% CI = 85.1-93.4%) and 75.1% (95% CI = 64.8-83.2%), respectively. Women
      who were hrHPV-negative, demonstrated an increased risk for extra-cervical
      malignancy (endometrium, fallopian tube, ovary). In women of 50y and older, a
      hrHPV-negative result was linked with a 18.0% chance of extra-cervical
      malignancy, while the chance of cervical pre-cancer and cancer was 0.4 and 0.0%,
      respectively. In conclusion, given the high risk of underlying CIN2+/AIS+, women
      with AGC should be referred directly to colposcopy. However, hrHPV test results
      in combination with the age, appears to improve the diagnostic process by
      distinguishing the risk for cervical versus non-cervical lesions.

PMID- 25583259
TI  - Coherent coupling of molecular resonators with a microcavity mode.
AB  - The optical hybridization of the electronic states in strongly coupled molecule
      cavity systems have revealed unique properties, such as lasing, room temperature
      polariton condensation and the modification of excited electronic landscapes
      involved in molecular isomerization. Here we show that molecular vibrational
      modes of the electronic ground state can also be coherently coupled with a
      microcavity mode at room temperature, given the low vibrational thermal
      occupation factors associated with molecular vibrations, and the collective
      coupling of a large ensemble of molecules immersed within the cavity-mode volume.
      This enables the enhancement of the collective Rabi-exchange rate with respect to
      the single-oscillator coupling strength. The possibility of inducing large shifts
      in the vibrational frequency of selected molecular bonds should have immediate
      consequences for chemistry. 

PMID- 25583257
TI  - Expression of a bacterial 3-dehydroshikimate dehydratase reduces lignin content
      and improves biomass saccharification efficiency.
AB  - Lignin confers recalcitrance to plant biomass used as feedstocks in agro
      processing industries or as source of renewable sugars for the production of
      bioproducts. The metabolic steps for the synthesis of lignin building blocks
      belong to the shikimate and phenylpropanoid pathways. Genetic engineering efforts
      to reduce lignin content typically employ gene knockout or gene silencing
      techniques to constitutively repress one of these metabolic pathways. Recently,
      new strategies have emerged offering better spatiotemporal control of lignin
      deposition, including the expression of enzymes that interfere with the normal
      process for cell wall lignification. In this study, we report that expression of
      a 3-dehydroshikimate dehydratase (QsuB from Corynebacterium glutamicum) reduces
      lignin deposition in Arabidopsis cell walls. QsuB was targeted to the plastids to
      convert 3-dehydroshikimate - an intermediate of the shikimate pathway - into
      protocatechuate. Compared to wild-type plants, lines expressing QsuB contain
      higher amounts of protocatechuate, p-coumarate, p-coumaraldehyde and p-coumaryl
      alcohol, and lower amounts of coniferaldehyde, coniferyl alcohol, sinapaldehyde
      and sinapyl alcohol. 2D-NMR spectroscopy and pyrolysis-gas chromatography/mass
      spectrometry (pyro-GC/MS) reveal an increase of p-hydroxyphenyl units and a
      reduction of guaiacyl units in the lignin of QsuB lines. Size-exclusion
      chromatography indicates a lower degree of lignin polymerization in the
      transgenic lines. Therefore, our data show that the expression of QsuB primarily
      affects the lignin biosynthetic pathway. Finally, biomass from these lines
      exhibits more than a twofold improvement in saccharification efficiency. We
      conclude that the expression of QsuB in plants, in combination with specific
      promoters, is a promising gain-of-function strategy for spatiotemporal reduction
      of lignin in plant biomass.

PMID- 25583262
TI  - Fructans, ascorbate peroxidase, and hydrogen peroxide in ryegrass exposed to
      ozone under contrasting meteorological conditions.
AB  - Ozone (O3) is the most abundant tropospheric oxidant as well as an important
      component of photochemical pollution. Once inside the plant, ozone can produce
      reactive oxygen species that change the antioxidative pool and the carbohydrate
      metabolism. The current study aimed to analyze whether the contents and the
      composition of the fructan, the ascorbate peroxidase activity, and the H2O2
      accumulation were changed in Lolium multiflorum ssp. italicum cv. Lema plants as
      response to short-term exposure to ozone and/or to different meteorological
      conditions, in two contrasting seasons (winter and summer). Results showed that
      higher solar radiation tends to decrease fructose content and, along with
      temperature, increases the ascorbate peroxidase (APX) activity. Such activity and
      levels of fructans practically did not vary during the time the experiment was
      being done, but APX daylight variation was modified by the ozone. Thus, the
      higher levels of this pollutant decreased the APX activity and increased fructose
      content, as well as changed the size of the fructan chains. Hydrogen peroxide
      (H2O2) accumulation was higher in plants that were fumigated with ozone when
      compared to the control, and it decreased throughout the day. As a conclusion,
      fructan contents increased when the APX activity decreased. It suggested that
      fructans could also help the defense system when there is a reduction on the APX
      activity in the plant. 

PMID- 25583261
TI  - BRCA1-IRIS inactivation overcomes paclitaxel resistance in triple negative breast
      cancers.
AB  - INTRODUCTION: Intrinsic or acquired chemoresistance is a major problem in
      oncology. Although highly responsive to chemotherapies such as paclitaxel, most
      triple negative breast cancer (TNBC) patients develop chemoresistance. Here we
      investigate the role of BRCA1-IRIS as a novel treatment target for TNBCs and
      their paclitaxel-resistant recurrences. METHODS: We analyzed the response of
      BRCA1-IRIS overexpressing normal mammary cells or established TNBC cells silenced
      from BRCA1-IRIS to paclitaxel in vitro and in vivo. We analyzed BRCA1-IRIS
      downstream signaling pathways in relation to paclitaxel treatment. We also
      analyzed a large cohort of breast tumor samples for BRCA1-IRIS, Forkhead box
      class O3a (FOXO3a) and survivin expression. Finally, we analyzed the effect of
      BRCA1-IRIS silencing or inactivation on TNBCs formation, maintenance and response
      to paclitaxel in an orthotopic model. RESULTS: We show that low concentrations of
      paclitaxel triggers BRCA1-IRIS expression in vitro and in vivo, and that BRCA1
      IRIS activates two autocrine signaling loops (epidermal growth factor (EGF)/EGF
      receptor 1 (EGFR)-EGF receptor 2 (ErbB2) and neurogulin 1 (NRG1)/ErbB2-EGF
      receptor 3 (ErbB3), which enhances protein kinase B (AKT) and thus survivin
      expression/activation through promoting FOXO3a degradation. This signaling
      pathway is intact in TNBCs endogenously overexpressing BRCA1-IRIS. These events
      trigger the intrinsic and acquired paclitaxel resistance phenotype known for
      BRCA1-IRIS-overexpressing TNBCs. Inactivating BRCA1-IRIS signaling using a novel
      inhibitory mimetic peptide inactivates these autocrine loops, AKT and survivin
      activity/expression, in part by restoring FOXO3a expression, and sensitizes TNBC
      cells to low paclitaxel concentrations in vitro and in vivo. Finally, we show
      BRCA1-IRIS and survivin overexpression is correlated with lack of FOXO3a
      expression in a large cohort of primary tumor samples, and that BRCA1-IRIS
      overexpression-induced signature is associated with decreased disease free
      survival in heavily treated estrogen receptor alpha-negative patients.
      CONCLUSIONS: In addition to driving TNBC tumor formation, BRCA1-IRIS
      overexpression drives their intrinsic and acquired paclitaxel resistance, partly
      by activating autocrine signaling loops EGF/EGFR-ErbB2 and NRG1/ErbB2-ErbB3.
      These loops activate AKT, causing FOXO3a degradation and survivin overexpression.
      Taken together, this underscores the need for BRCA1-IRIS-specific therapy and
      strongly suggests that BRCA1-IRIS and/or signaling loops activated by it could be
      rational therapeutic targets for advanced TNBCs.

PMID- 25583263
TI  - Identifying sources of Pb pollution in urban soils by means of MC-ICP-MS and TOF
      SIMS.
AB  - Lead pollution was evaluated in 17 urban soils from parks and gardens in the city
      of Vigo (NW Spain). The Pb isotope ratios ((207)Pb/(206)Pb, (208)Pb/(204)Pb,
      (206)Pb/(204)Pb and (208)Pb/(206)Pb) were determined after being measured by MC
      ICP-MS. The association of the isotopes ((204)Pb, (206)Pb, (207)Pb and (208)Pb)
      with the different components of the soil was studied using TOF-SIMS. The
      isotopic ranges obtained for the samples were between 1.116 and 1.203
      ((206)Pb/(207)Pb), 2.044-2.143 ((208)Pb/(206)Pb), 37.206-38.608
      ((208)Pb/(204)Pb), 15.5482-15.6569 ((207)Pb/(204)Pb) and 17.357-18.826
      ((206)Pb/(204)Pb). The application of the three-end-member model indicates that
      the Pb derived from petrol is the main source of Pb in the soils (43.51% on
      average), followed by natural or geogenic Pb (39.12%) and industrial emissions
      (17.37%). The emissions derived from coal combustion do not appear to influence
      the content of Pb in the soil. TOF-SIMS images show that the Pb mainly interacts
      with organic matter. This technique contributes to the understanding of the
      association of anthropogenic Pb with the components of the soil, as well as the
      particle size of these associations, thus allowing the possible sources of Pb to
      be identified.

PMID- 25583260
TI  - The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylates in a metal
      independent manner.
AB  - The human Tribbles (TRB)-related pseudokinases are CAMK (calcium/calmodulin
      dependent protein kinase)-related family members that have evolved a series of
      highly unusual motifs in the 'pseudocatalytic' domain. In canonical kinases,
      conserved amino acids bind to divalent metal ions and align ATP prior to
      efficient phosphoryl-transfer to substrates. However, in pseudokinases, atypical
      residues give rise to diverse and often unstudied biochemical and structural
      features that are thought to be central to cellular functions. TRB proteins play
      a crucial role in multiple signalling networks and overexpression confers cancer
      phenotypes on human cells, marking TRB pseudokinases out as a novel class of drug
      target. In the present paper, we report that the human pseudokinase TRB2 retains
      the ability to both bind and hydrolyse ATP weakly in vitro. Kinase activity is
      metal-independent and involves a catalytic lysine residue, which is conserved in
      TRB proteins throughout evolution alongside several unique amino acids in the
      active site. A similar low level of autophosphorylation is also preserved in the
      closely related human TRB3. By employing chemical genetics, we establish that the
      nucleotide-binding site of an 'analogue-sensitive' (AS) TRB2 mutant can be
      targeted with specific bulky ligands of the pyrazolo-pyrimidine (PP) chemotype.
      Our analysis confirms that TRB2 retains low levels of ATP binding and/or
      catalysis that is targetable with small molecules. Given the significant clinical
      successes associated with targeting of cancer-associated kinases with small
      molecule inhibitors, it is likely that similar approaches will be useful for
      further evaluating the TRB pseudokinases, with the translation of this
      information likely to furnish new leads for drug discovery. 

PMID- 25583264
TI  - Chronic exposure to pollutants in Madin Reservoir (Mexico) alters oxidative
      stress status and flesh quality in the common carp Cyprinus carpio.
AB  - Madin Reservoir (MR) is located on the Rio Tlalnepantla in Mexico. Previous
      studies seeking to identify pollutants at this site evidence that MR water
      contains a considerable metal load as well as nonsteroidal anti-inflammatory
      drugs (NSAIDs) at concentrations above those determined suitable for aquatic
      life. This study aimed to evaluate whether chronic exposure to pollutants in MR
      alters oxidative stress status and flesh quality in muscle of the common carp
      Cyprinus carpio. The following biomarkers were evaluated in muscle of carp caught
      in the general area of discharge from the town of Viejo Madin: hydroperoxide
      content (HPC), lipid peroxidation (LPX), protein carbonyl content (PCC), and
      activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT),
      and glutathione peroxidase (GPx). Physicochemical and textural properties of
      muscle were also evaluated. Results show that the metals Al and Fe were
      accumulated in muscle of C. carpio at levels of 21.3 and 29.6 MUg L(-1),
      respectively, and the NSAIDs diclofenac, ibuprofen, and naproxen at levels from
      0.08 to 0.21 ng L(-1). Fish exposed to discharge from the town of Viejo Madin
      showed significant increases in HPC (9.77 %), LPX (69.33 %), and PCC (220 %) with
      respect to control specimens (p < 0.05). Similarly, enzyme activity increased
      significantly: SOD (80.82 %), CAT (98.03 %), and GPx (49.76 %). In muscle,
      physicochemical properties evidenced mainly significant reductions compared to
      control values while textural properties showed significant increases. Thus,
      water in this reservoir is contaminated with xenobiotics that alter some
      biological functions in C. carpio, a fish species consumed by the local human
      population.

PMID- 25583265
TI  - Rabbit antithymocyte globulin as first-line therapy for severe aplastic anemia.
AB  - Rabbit antithymocyte globulin (rATG) was proven effective as salvage therapy for
      refractory aplastic anemia (AA), or for relapse after initial therapy with horse
      ATG (hATG). Several clinical trials were performed to assess the efficiency of
      rATG as a first-line therapy for AA patients; however, their results were
      variable. The aim of the present study was to assess hematologic response and
      survival in severe AA (SAA) and very severe AA (VSAA) patients treated with rATG
      and cyclosporin A (CsA) in our center. The factors involved in these outcomes
      were also explored. A total of 292 patients with newly diagnosed, acquired SAA or
      VSAA received a combination of rATG and CsA as first-line therapy, and the
      results were retrospectively assessed. The median age was 18 years (range = 2-73
      years). The early death rate was 5.5%, and the total response rates were 49.0%
      (143 responders), 60.3% (176 responders), 65.8% (192 responders), and 68.5% (200
      responders) at 3, 6, 9, and 12 months, respectively, after immunosuppressive
      therapy. In multivariate analysis, initial response to granulocyte colony
      stimulating factor (G-CSF) was the predictive factor for response to therapy at
      12 months. Median follow-up of surviving patients was 34 months (range = 0-117
      months). Five-year overall survival was 83.2%, and the 5-year, event-free
      survival was 67.2%. Independent prognostic factors for overall survival were
      neutrophil count and achievement of any response following rATG therapy. Our
      results indicate that rATG/CsA is a safe and effective first-line treatment for
      SAA/VSAA.

PMID- 25583267
TI  - Detection of acute myocardial ischemic injury by gender using a novel cardiac
      electrical biomarker.
AB  - OBJECTIVE: The objective of this study us to stratify by gender a new cardiac
      electrical biomarker (CEB) diagnostic accuracy for detection of acute myocardial
      ischemic injury (AMII). METHODS: This is a noninferiority retrospective, case
      control, blinded study of 310 archived measured electrocardiograms (ECGs)
      acquired from 218 men and 92 women. The CEB is constructed from the derived ECG
      (dECG) synthesized from 3 leads. Electrocardiograms were included if acquired
      less than or equal to 1 day from patient presentation. Electrocardiograms were
      interpreted by 2 blinded physicians and adjudicated by consensus. Standard ST
      analyses and computerized ECG interpretations were active controls.
      Electrocardiograms were excluded for noise and baseline wander, age younger than
      18 years, and ectopic beats in the 10-second ECG acquisition. Diagnostic accuracy
      measures of sensitivity, specificity, positive and negative predictive values,
      and likelihood ratios were stratified by gender. Measured vs derived ECG
      correlations were quantitatively compared using Pearson correlation and
      qualitatively by percent agreement methodology. RESULTS: The CEB sensitivities
      for AMII detection in men and women were 93.9% and 90.5%, respectively, and CEB
      specificities were 90.7% and 95.2%, respectively, and were superior to active
      controls. Derived and measured ECGs showed high correlation for both men and
      women with r = 0.857 and r = 0.893, respectively. Reference standard intra
      agreement analysis for measured ECGs and dECGs with AMII was 99.4%. CONCLUSIONS:
      The CEB demonstrates high diagnostic accuracy for detection of AMII in men and
      women. The ECG can be derived with accuracy from 3 leads. This technology is an
      efficient real-time method of identifying patients with AMII who are being
      monitored in acute care settings.

PMID- 25583266
TI  - The topographical arrangement of cutoff spatial frequencies across lower and
      upper visual fields in mouse V1.
AB  - The visual response to spatial frequency (SF), a characteristic of spatial
      structure across position in space, is of particular importance for animal
      survival. A natural challenge for rodents is to detect predators as early as
      possible while foraging. Whether neurons in mouse primary visual cortex (V1) are
      functionally organized to meet this challenge remains unclear. Combining
      intrinsic signal optical imaging and single-unit recording, we found that the
      cutoff SF was much greater for neurons whose receptive fields were located above
      the mouse. Specifically, we discovered that the cutoff SF increased in a gradient
      that was positively correlated with the elevation in the visual field. This
      organization was present at eye opening and persisted through adulthood. Dark
      rearing delayed the maturation of the cutoff SF globally, but had little impact
      on the topographical organization of the cutoff SF, suggesting that this regional
      distribution is innately determined. This form of cortical organization of
      different SFs may benefit the mouse for detection of airborne threats in the
      natural environment. 

PMID- 25583268
TI  - Reversible cerebral vasoconstriction syndrome as a cause of thunderclap headache:
      a retrospective case series study.
AB  - Thunderclap headache is a common emergency department presentation. Although
      subarachnoid hemorrhage (SAH) should be the first diagnosis to exclude,
      reversible cerebral vasoconstriction syndrome (RCVS) is an important alternative
      cause, which may be commoner than appreciated. Reversible cerebral
      vasoconstriction syndrome is characterized by multifocal narrowing of cerebral
      arteries, typically manifested by acute, severe headache with or without
      neurologic deficits. To compare and discuss the clinical and radiologic
      characteristics of patients with RCVS. We report 4 cases of RCVS, presenting at a
      single unit in 1 year. All presented with thunderclap headache, whereas half of
      them had additional neurologic symptoms such as right homonymous hemianopia,
      right-sided weakness, and slurred speech. Brain computed tomography was normal in
      2 of our patients, but subsequent cerebrospinal fluid analysis revealed
      xanthochromia consistent with SAH. The remaining 2 patients demonstrated
      intracerebral hemorrhage on computed tomography. All of our patients underwent
      digital subtraction angiography that showed segmental narrowing and dilatation of
      one or more cerebral arteries without any signs of aneurysm. Repeat digital
      subtraction angiography after 3 months was entirely normal prompting the
      diagnosis of RCVS. Thunderclap headache requires urgent workup to identify the
      underlying cause. Although SAH is the most important diagnosis to exclude in the
      first instance, emergency physicians should be aware of other causes and how they
      present, such as RCVS. Early recognition of this condition is important in order
      to remove precipitants, avoid unnecessary investigations, and inform patients
      about their prognosis.

PMID- 25583270
TI  - Sharing State Mental Health Data for Research: Building Toward Ongoing Learning
      in Mental Health Care Systems.
AB  - With the rise of "big data," the opportunities to use administrative and clinical
      data to evaluate impact of state level program initiatives are greatly expanded.
      The National Institute of Mental Health has in recent years supported research
      studies pooling data across states to address state-relevant questions. This
      commentary summarizes these activities and describes future platforms that may
      enhance ongoing work in this area.

PMID- 25583271
TI  - Service Use Findings from the Child STEPs Effectiveness Trial: Additional Support
      for Modular Designs.
AB  - This study expands upon the Chorpita et al. (J Consult Clin Psychol 81:999-1009,
      2013) findings by examining the impact of treatment protocol on youths' service
      utilization up to 2 years after starting an episode of: standard manualized
      treatment (Standard); modular treatment (Modular); or usual care (UC). Results
      showed that youths who received Modular accessed fewer service settings at their
      one-year follow-up relative to youths who received Standard or UC. Findings
      suggest that modular treatment may offer an advantage over standardized treatment
      manuals and UC in terms of sustained clinical benefits, and highlight the
      importance of treatment design considerations for service systems.

PMID- 25583269
TI  - Amygdala-prefrontal interactions in (mal)adaptive learning.
AB  - The study of neurobiological mechanisms underlying anxiety disorders has been
      shaped by learning models that frame anxiety as maladaptive learning. Pavlovian
      conditioning and extinction are particularly influential in defining learning
      stages that can account for symptoms of anxiety disorders. Recently, dynamic and
      task related communication between the basolateral complex of the amygdala (BLA)
      and the medial prefrontal cortex (mPFC) has emerged as a crucial aspect of
      successful evaluation of threat and safety. Ongoing patterns of neural signaling
      within the mPFC-BLA circuit during encoding, expression and extinction of
      adaptive learning are reviewed. The mechanisms whereby deficient mPFC-BLA
      interactions can lead to generalized fear and anxiety are discussed in learned
      and innate anxiety. Findings with cross-species validity are emphasized. 

PMID- 25583274
TI  - Effects of treadmill versus overground soccer match simulations on biomechanical
      markers of anterior cruciate ligament injury risk in side cutting.
AB  - This study aimed to investigate whether treadmill versus overground soccer match
      simulations have similar effects on knee joint mechanics during side cutting.
      Nineteen male recreational soccer players completed a 45-min treadmill and
      overground match simulation. Heart rate (HR) and rating of perceived exertion
      (RPE) were recorded every 5 min. Prior to exercise (time 0 min), at "half-time"
      (time 45 min) and 15 min post-exercise (time 60 min), participants performed five
      trials of 45 degrees  side-cutting manoeuvres. Knee abduction moments and knee
      extension angles were analysed using two-way repeated measures analysis of
      variance (alpha = 0.05). Physiological responses were significantly greater
      during the overground (HR 160 +/- 7 beats ? min(-1); RPE 15 +/- 2) than the
      treadmill simulation (HR 142 +/- 5 beats ? min(-1); RPE 12 +/- 2). Knee extension
      angles significantly increased over time and were more extended at time 60 min
      compared with time 0 min and time 45 min. No significant differences in knee
      abduction moments were observed. Although knee abduction moments were not altered
      over time during both simulations, passive rest during half-time induced changes
      in knee angles that may have implications for anterior cruciate ligament injury
      risk.

PMID- 25583273
TI  - Selection of the treatment effect for sample size determination in a superiority
      clinical trial using a hybrid classical and Bayesian procedure.
AB  - Specification of the treatment effect that a clinical trial is designed to detect
      (thetaA) plays a critical role in sample size and power calculations. However, no
      formal method exists for using prior information to guide the choice of thetaA.
      This paper presents a hybrid classical and Bayesian procedure for choosing an
      estimate of the treatment effect to be detected in a clinical trial that formally
      integrates prior information into this aspect of trial design. The value of
      thetaA is found that equates the pre-specified frequentist power and the
      conditional expected power of the trial. The conditional expected power averages
      the traditional frequentist power curve using the conditional prior distribution
      of the true unknown treatment effect theta as the averaging weight. The Bayesian
      prior distribution summarizes current knowledge of both the magnitude of the
      treatment effect and the strength of the prior information through the assumed
      spread of the distribution. By using a hybrid classical and Bayesian approach, we
      are able to formally integrate prior information on the uncertainty and
      variability of the treatment effect into the design of the study, mitigating the
      risk that the power calculation will be overly optimistic while maintaining a
      frequentist framework for the final analysis. The value of thetaA found using
      this method may be written as a function of the prior mean MU0 and standard
      deviation tau0, with a unique relationship for a given ratio of MU0/tau0. Results
      are presented for Normal, Uniform, and Gamma priors for theta. 

PMID- 25583272
TI  - Self-Care for Older People (SCOPE): a cluster randomized controlled trial of self
      care training and health outcomes in low-income elderly in Singapore.
AB  - Population aging is associated with a higher prevalence of chronic health
      conditions. Previous studies have shown that older persons, specifically those
      with chronic conditions, often lack sufficient knowledge about their condition
      and thus frequently have poor self-care skills. Efforts to increase general
      health screenings and improve access to chronic condition management resources
      are hampered by a lack of disease and health awareness. Self-Care for Older
      People (SCOPE) study, a cluster randomized controlled trial in Singapore, was
      designed to evaluate the impact of a self-care program for chronic disease
      awareness and management of specific health measures and quality of life of older
      people over eighteen months. SCOPE provided self-care education targeted at older
      people with low income and low education in order to improve health-related
      knowledge. A total of 378 low-income older people with no or minimal disability,
      defined as having difficulty in one or more activities of daily living (ADL),
      were recruited from senior activity centers. The measurements taken included self
      reported health conditions, health and disease knowledge questions, and
      biomarkers (HbA1c, blood pressure, peak expiratory flow, lipid panel, albumin,
      and creatinine). SCOPE was also designed to provide information for policy makers
      on chronic disease burden and healthcare facility utilization among community
      dwelling older adults. TRIAL REGISTRATION NUMBER: NCT01672177.

PMID- 25583275
TI  - Longitudinal psychological outcomes of the small-scale nursing home model: a
      latent growth curve zero-inflated Poisson model.
AB  - BACKGROUND: This study aims to examine the longitudinal effects of a small-scale
      nursing home model on the change rates of psychological outcomes by comparing
      green house (GH) and traditional nursing home residents. METHODS: A total of 242
      residents (93 GH and 149 traditional home residents) who resided at the home
      least 6 months from admission. Four minimum dataset assessments every six months
      from admission were included. The main psychological outcomes were depressive
      mood, and social engagement. The main independent variable was the facility type
      that the resident resided in: a GH or traditional unit. Age, gender, ADL
      function, and cognitive function at admission were controlled in the model. A
      zero-inflated Poisson (ZIP) growth curve model was utilized to compare change
      rates of two psychological outcomes between the two groups taking into account
      many zero counts of two outcome measures. RESULTS: A rate of increase in
      depressive symptoms for GH home residents was higher than that of traditional
      home residents (beta = 0.135, p-value = 0.025). GH home residents had a lower
      rate of increase of the probability of "not being socially engaged" over time
      compared to traditional home residents (beta = -0.274, p-value = 0.010).
      CONCLUSION: The GH nursing home model had a longitudinal effect on increasing the
      probability of residents' social engagement over time, but also increasing the
      recognition of depressive symptoms compared to traditional nursing homes.

PMID- 25583276
TI  - Retrospective Study on Fatal Melioidosis in Captive Zoo Animals in Thailand.
AB  - Melioidosis is caused by Burkholderia pseudomallei and is an important zoonotic
      infectious disease causing high mortality from fulminant septicaemia in humans
      and a wide variety of animal species. The incidence of fatal melioidosis in zoo
      animals has been significant in many Thai zoos. A total number of 32 cases were
      evaluated throughout the Thai zoo animal populations. The highest prevalence of
      disease has been reported from the north-eastern region followed by the zoos in
      the southern part of the country, approximately 47% and 38%, respectively, while
      the other zoos reported sporadic infections. Herbivores and non-human primates
      were the most commonly affected animals with incidences of 59% and 28%,
      respectively. This appears to be a seasonal correlation with the highest
      incidence of melioidosis in zoo animals reported in the rainy season (44%) or
      subdivided monthly in June (19%) followed by September and November (16% and 12%,
      respectively). The route of infection and the incubation period still remain
      unclear. This retrospective study examined the clinical presentation in various
      zoo species, pathological findings and epidemiological data as well as conducting
      an in depth literature review. 

PMID- 25583277
TI  - Myxoid leiomyosarcoma of the uterus with mature adipocytes and numerous bizarre
      multinucleated giant cells.

PMID- 25583278
TI  - Taking the discovery approach in integrative taxonomy: decrypting a complex of
      narrow-endemic Alpine harvestmen (Opiliones: Phalangiidae: Megabunus).
AB  - Species delimitation is fundamental for biological studies, yet precise
      delimitation is not an easy task, and every involved approach has an inherent
      failure rate. Integrative taxonomy, a method that merges multiple lines of
      evidence, can profoundly contribute to reliable alpha-taxonomy and shed light on
      the processes behind speciation. In this study, we explored and validated species
      limits in a group of closely related Megabunus harvestmen (Eupnoi, Phalangiidae)
      endemic to the European Alps. Without a priori species hypotheses, we used
      multiple sources of inference, including mitochondrial and multilocus nuclear
      DNA, morphometrics and chemistry. The results of these discovery approaches
      revealed morphological crypsis and multiple new species within two of the five
      hitherto known species. Based on our analyses, we discussed the most plausible
      evolutionary scenarios, invoked the most reasonable species hypotheses and
      validated the new species limits. Building upon the achieved rigour, three new
      species, Megabunus cryptobergomas Muster and Wachter sp. nov., Megabunus
      coelodonta Muster and Steiner sp. nov., and Megabunus lentipes Muster and
      Komposch sp. nov., are formally described. In addition, we provide a dichotomous
      morphological key to the Megabunus species of the Alps. Our work demonstrates the
      suitability of integrative, discovery-based approaches in combination with
      validation approaches to precisely characterize species and enabled us to
      implement nomenclatural consequences for this genus. 

PMID- 25583279
TI  - Neoadjuvant/adjuvant treatment of high-risk retinoblastoma: a report from the
      German Retinoblastoma Referral Centre.
AB  - BACKGROUND: Retinoblastoma can extend beyond the structures of the eye, where
      cells can enter the bloodstream and cause metastases. Various types of protocols
      for adjuvant treatment risk-adapted according to histopathological risk factors
      are used worldwide. METHODS: Between 1997 and 2009, 420 children were diagnosed
      with retinoblastoma at the German Retinoblastoma Referral Centre and risk factors
      were assessed. Patients with post-laminar optic nerve infiltration or choroid or
      minor scleral invasion received six courses of adjuvant chemotherapy using
      vincristine, etoposide, carboplatin and cyclophosphamide (group 1). Patients with
      microscopic extension beyond the sclera to the resection margin of the optic
      nerve or potential spread due to vitrectomy received chemotherapy plus orbital
      radiotherapy (group 2). Neoadjuvant chemotherapy was performed in patients with
      local extraocular invasion detected on MRI. RESULTS: Following this protocol, 42
      of the 420 patients and 21 referred from other centres showed high-risk
      histopathological factors qualifying for adjuvant therapy (57 in group 1 and 6 in
      group 2). Seven of the 63 patients received neoadjuvant and adjuvant treatment.
      During a mean follow-up of 5.8 (range 0.4-15.4) years, one of six patients in
      group 2 developed metastases and died. No patients died from toxicity. The 5-year
      overall survival was 100% for group 1 and 80% for group 2. CONCLUSIONS: This
      retrospective single-site study reveals a 10% incidence of high-risk features in
      children with retinoblastoma diagnosed at the German Retinoblastoma Referral
      Centre. Overall survival rates of 98.3% underline the safety of this adjuvant
      chemotherapy protocol and its efficiency in preventing metastasis.

PMID- 25583280
TI  - Influence of graft size on graft survival following Descemet stripping automated
      endothelial keratoplasty.
AB  - PURPOSE: To evaluate graft size on outcome following Descemet stripping automated
      endothelial keratoplasty (DSAEK) METHODS: Consecutive patients who had undergone
      a DSAEK for Fuchs endothelial dystrophy (FED) and pseudophakic bullous
      keratopathy (PBK) with at least 1 year of follow-up. Patients were divided into
      three groups according to the size of the donor trephine: <9, 9 and 9.5 mm. Main
      outcomes were postoperative best corrected visual acuity (BCVA) and graft
      failure. Grafts were prepared using an automated microkeratome. For larger grafts
      (>=9 mm), a manual dissection of the residual peripheral ring of anterior lamella
      was performed before trephination. Donor age, endothelial cell density (ECD) and
      postmortem times; recipient details including risk factors, comorbidity, surgical
      complications and postoperative BCVA and graft survival were analysed. RESULTS:
      Of 174 patients, 131 were included: 84 (64%) with FED and 47 (36%) with PBK. Mean
      preoperative and postoperative BCVA were 1.01+/-0.76 and 0.2+/-0.2 logMAR,
      respectively, at 12 months with 80.5% achieving 20/40 or better. Postoperative
      BCVA was significantly associated with ECD (p=0.005), PBK or FED (p=0.004), risk
      factors (p=0.007) and comorbidity (p=0.016). Eleven patients (8.40%) experienced
      endothelial graft failure; 17.86% for <9 mm, 7.69% for 9 mm and 3.84% for 9.5 mm
      trephine sized grafts. Graft failure was significantly associated with ECD
      (p=0.039) and graft trephine size (p=0.04). CONCLUSIONS: Larger grafts occupy a
      smaller chord length in the eye than the trephine size and are expected to
      provide 10%-20% more endothelial cells. Increased graft size and donor ECD is
      significantly associated with a reduced graft failure rate.

PMID- 25583281
TI  - Improving survival of retinoblastoma in Uganda.
AB  - BACKGROUND: Diagnostic delay results in relatively high mortality among children
      with retinoblastoma in Uganda, where treatment was limited to surgery and, for
      some, radiotherapy. In order to improve outcomes, a simple programme of
      neoadjuvant and adjuvant chemotherapy was introduced. Here we report survival
      before and after this change to medical practice. METHODS: Affordable standard
      off-patent chemotherapy agents were administered by trained paramedical staff to
      groups of patients at the same time. Survival before and after the introduction
      of chemotherapy was monitored. Between 2006 and 2013 a total of 270 patients with
      retinoblastoma were included, 181 treated prior to chemotherapy and 89 after
      (beginning in 2009). We had 94% follow-up and 249 had histological verification
      of diagnosis. RESULTS: Using a proportional hazards model adjusted for age, sex
      and laterality, children treated after chemotherapy was introduced had a 37%
      lower risk of dying (HR 0.63, 95% CI 0.41 to 0.99) compared with children treated
      before. Prior to the introduction of chemotherapy only 15% of children who
      survived bilateral disease retained vision after treatment compared with 71%
      after chemotherapy. CONCLUSIONS: The introduction of chemotherapy proved safe and
      cost-effective in non-specialist hands and was associated with significant
      improvements in survival and, among bilateral cases, in preserving vision.

PMID- 25583282
TI  - Intraocular pressure and coronary artery calcification in asymptomatic men and
      women.
AB  - OBJECTIVE: We evaluated the relationship between intraocular pressure (IOP) and
      the risk of coronary artery calcification as a predictable marker of
      cardiovascular disease (CVD) in a large study of asymptomatic men and women.
      METHODS: A cross-sectional study was performed in 10 732 asymptomatic men and
      women without diagnosed CVD or glaucoma. Coronary artery calcium (CAC) was
      measured by cardiac CT. The IOPs of all participants were measured by experienced
      nurses with a non-contact tonometer and automatic air puff control. Logistic
      regression was used to estimate the OR (95% CI) for the presence of CAC (score
      >0) with IOP quartiles. RESULTS: The prevalence of detectable CAC was 13.7% in
      men and 4.3% in women. Increasing levels of right IOP were significantly
      associated with an increased prevalence of CAC. After adjusting for age, sex,
      smoking, alcohol intake, physical activity, body mass index, educational level,
      centre, family history of CVD, use of dyslipidaemia medication, diabetes,
      hypertension, total cholesterol, high density lipoprotein cholesterol and
      triglycerides, the ORs for CAC score >0, comparing 2-4 quartiles of the right IOP
      to the lowest quartiles, were 1.32 (95% CI 1.09 to 1.59), 1.20 (95% CI 0.98 to
      1.46), and 1.28 (95% CI 1.05 to 1.56), respectively. These associations did not
      differ by clinically relevant subgroups. CONCLUSIONS: A higher IOP is
      significantly associated with the presence of CAC regardless of conventional
      cardiovascular risk factors. The present study provides more insight into
      understanding the process of subclinical atherosclerosis in CVD and the
      relationship with a higher IOP as a common pathophysiology.

PMID- 25583283
TI  - Effectiveness and safety of dexamethasone implants for post-surgical macular
      oedema including Irvine-Gass syndrome: the EPISODIC study.
AB  - AIM: To assess the effectiveness and safety of intravitreal dexamethasone
      implants for treating post-surgical macular oedema, including Irvine-Gass
      syndrome refractory to first-line treatments. METHODS: Descriptive,
      observational, retrospective, consecutive, uncontrolled, multicentre, national
      case series. 50 patients were included in the study between March 2011 and June
      2013 with a minimum 6 months follow-up. At baseline, each patient received a
      dexamethasone implant 0.7 mg (Ozurdex). Best-corrected visual acuity (BCVA),
      central subfield macular thickness (CSMT), and intraocular pressure (IOP) were
      measured at baseline and then monthly. The main outcome measure was the mean
      change in BCVA (in ETDRS letters (Early Treatment Diabetic Retinopathy Study): L)
      RESULTS: Baseline mean+/-SD BCVA was 55.7+/-15.4 L. At month 2, BCVA was 71.8+/
      10.5 L and 61.2% of patients had an increase of more than 15 letters. Baseline
      mean CSMT was 544+/-117.2 MUm and this decreased to 302 MUm at month 2. Anatomic
      and functional recurrences were both first detected from month 3 and continued
      throughout follow-up, with values consistently above baseline. The peak in IOP
      was reached in month 1 with mean IOP of 15.3+/-4.6 mm Hg. Of the 39/50 patients
      followed up for 12 months, 49% received a second injection. The anatomic and
      functional response and safety patterns were similar to that obtained with the
      first intravitreal injection, demonstrating Ozurdex's reproducibility. However,
      more than half of the patients followed-up for at least 1 year presented neither
      functional nor anatomical recurrence. CONCLUSIONS: Ozurdex would appear to be an
      interesting alternative therapy for treating post-surgical macular oedema,
      including Irvine-Gass syndrome refractory to first-line treatments.

PMID- 25583284
TI  - Myeloid sarcoma of the breast misdiagnosed as poorly differentiated mammary
      carcinoma with lobular features.

PMID- 25583285
TI  - A p-menth-1-ene-4,7-diol (EC-1) from Eucalyptus camaldulensis Dhnh. triggers
      apoptosis and cell cycle changes in Ehrlich ascites carcinoma cells.
AB  - Anticancer activities of p-menth-1-ene-4,7-diol (EC-1) isolated from Eucalyptus
      camaldulensis Dhnh. were studied on Ehrlich ascites carcinoma (EAC) cells by MTT
      (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Anticancer
      activities also analyzed in EAC-bearing mice by assessment of cancer growth
      inhibition, changes in cancer volume, changes in life span, and hematological
      parameters. Apoptosis was analyzed by fluorescence microscope, DNA fragmentation
      assay, and flow cytometry. The expression of apoptosis-related genes, Bcl-2, Bcl
      X, PARP-1, p53, and Bax, were analyzed using polymerase chain reaction (PCR). EC
      1 significantly inhibited proliferation of EAC cells in vivo and restored the
      altered hematological parameters of EAC-bearing mice. Cytological observation by
      fluorescence microscope showed apoptosis of EAC cells upon treatment with EC-1.
      Also, DNA fragmentation assay revealed EAC cells' apoptosis following EC-1
      treatment. Increased mRNA expressions of p53 and Bax genes and negative
      expressions of Bcl-2 and Bcl-X were observed in cells treated with EC-1. These
      findings confirmed the induction of apoptosis by EC-1. In addition, MTT assay
      showed dose-dependent anticancer activity of EC-1 against EAC cell. Cell cycle
      analysis revealed that EC-1 treatment caused suppression of EAC cells at S phase.
      To conclude, EC-1 is a novel anticancer compound and showed antiproliferative and
      apoptotic activities in cellular and mice models.

PMID- 25583286
TI  - Is post-pneumonia chest X-ray for lung malignancy useful? Results of an audit of
      current practice.
AB  - BACKGROUND/AIM: Patients with community-acquired pneumonia (CAP) are often
      screened with repeat chest X-ray within 6-12 weeks following an admission. This
      practice is aimed to detect underlying lung malignancy, which can be difficult to
      identify initially when an acute infiltrate is present on X-ray. We conducted a
      study on the use of follow-up chest X-rays after an admission with CAP to
      determine the yield of suspected or diagnosed cancer. METHODS: During the 2-year
      period, January 2010-January 2012, we evaluated all patients over the age of 50
      who had no previous history of lung cancer and were admitted to Hutt Hospital
      with CAP. RESULTS: A total of 302 patients was included. Of these, 53% received a
      follow-up chest X-ray within 6-12 weeks after admission. A total of six patients
      (2.0%) was diagnosed with lung cancer based on a chest X-ray within 6-12 weeks
      after admission. After a median period of follow up of 19.5 months, a further
      five patients who had normal chest X-ray were diagnosed with lung malignancy.
      CONCLUSION: The majority of patients were screened with follow-up X-rays. The
      yield from a 6- to 12-week chest X-ray following CAP is low, which is consistent
      with previous studies. The development of clear guidelines to ensure
      identification of patient groups at significantly high risk of lung cancer is
      important to increase the sensitivity of screening. High yielding strategies,
      such as low-dose computed tomography, should be considered as an alternative.

PMID- 25583287
TI  - Dermoscopic characterization of longitudinal melanocytic lesions on acral skin.

PMID- 25583289
TI  - Generalized favus: the story of a legendary case of tinea favosa.
AB  - From the moment the Olavide Museum opened its doors in 1882 until its content was
      packed up around 1965 and lost sight of for a time, it underwent a succession of
      changes. Some of those changes cannot be fully documented now because the
      archives of the Provincial Council (Diputacion) of Madrid were lost during the
      Spanish Civil War. The museum was initially housed in Hospital de San Juan de
      Dios, in the neighborhood of Atocha. Because this hospital treated mainly
      venereal diseases, much of the information we have about it comes from newspapers
      or magazines of the period, and their accounts were often sensationalistic. When
      a large number of the museum's wax figures were rediscovered, along with a great
      many accompanying documents, in December 2005, the material allowed 3 sculptors
      Zofio, Barta, and Lopez Alvarez-to be identified. Case histories corresponding to
      the figures were also among the papers found. As a result, the truth about
      certain legends associated with the museum, the sculptors, and the patients could
      be unraveled. Among the patients whose stories were brought to light was one
      referred to as the boy with generalized tinea favosa, or crusted ringworm. 

PMID- 25583288
TI  - Fragmented Health Care Delivery in Ichthyosis.

PMID- 25583290
TI  - Impaired neuronal operation through aberrant intrinsic plasticity in epilepsy.
AB  - OBJECTIVE: Patients with temporal lobe epilepsy often display cognitive
      comorbidity with recurrent seizures. However, the cellular mechanisms underlying
      the impairment of neuronal information processing remain poorly understood in
      temporal lobe epilepsy. Within the hippocampal formation neuronal networks
      undergo major reorganization, including the sprouting of mossy fibers in the
      dentate gyrus; they establish aberrant recurrent synapses between dentate granule
      cells and operate via postsynaptic kainate receptors. In this report, we tested
      the hypothesis that this aberrant local circuit alters information processing of
      perforant path inputs constituting the major excitatory afferent pathway from
      entorhinal cortex to dentate granule cells. METHODS: Experiments were performed
      in dentate granule cells from control rats and rats with temporal lobe epilepsy
      induced by pilocarpine hydrochloride treatment. Neurons were recorded in patch
      clamp in whole cell configuration in hippocampal slices. RESULTS: Our present
      data revealed that an aberrant readout of synaptic inputs by kainate receptors
      triggered a long-lasting impairment of the perforant path input-output operation
      in epileptic dentate granule cells. We demonstrated that this is due to the
      aberrant activity-dependent potentiation of the persistent sodium current
      altering intrinsic firing properties of dentate granule cells. INTERPRETATION: We
      propose that this aberrant activity-dependent intrinsic plasticity, which
      lastingly impairs the information processing of cortical inputs in dentate gyrus,
      may participate in hippocampal-related cognitive deficits, such as those reported
      in patients with epilepsy.

PMID- 25583291
TI  - A patient with acute kidney pain and high blood pressure.
AB  - This case presented challenging diagnostic and management issues in a young
      healthy man who presented with abdominal pain and new-onset hypertension. The
      differential diagnosis evolved over the course of the clinical presentation. The
      patient had severe vascular involvement of his renal and basal cerebral arteries
      that initially was assumed to be due to a vasculitic process or hypercoagulable
      state. Finally it became apparent that the patient did not have a systemic
      illness but rather a localized vascular disease most likely due to segmental
      arterial mediolysis, a rare, under-recognized condition that can potentially be
      fatal. This condition is often difficult to distinguish from fibromuscular
      dysplasia. It is important to recognize and correctly diagnose the condition,
      particularly in the acute phase of the disease, because delay in diagnosis can
      contribute to morbidity and mortality. 

PMID- 25583293
TI  - Introduction: Role of the medical director series.

PMID- 25583294
TI  - Getting the balance right: adverse events of therapy in anti-neutrophil cytoplasm
      antibody vasculitis.
AB  - Antineutrophil cytoplasm antibody associated systemic vasculitides (AASV) have
      traditionally been managed with a combination of cyclophosphamide and
      glucocorticoids during the induction phase, followed by azathioprine in the
      maintenance phase. Whilst these therapies have markedly improved the prognosis in
      AASV, treatment related adverse events remain a major challenge and include
      complications such as infection, glucocorticoid related side effects, malignancy,
      cardiovascular disease, infertility and death. Newer biologic therapies have been
      shown to demonstrate equivalent efficacy as cyclophosphamide for remission but
      the hoped for reduction in adverse events has yet to be realised. More recent
      efforts have been focused on refining existing therapeutic regimens and
      strategies, tailoring individual treatment to disease severity, patient age and
      kidney function to derive maximum treatment efficacy while minimising treatment
      toxicity. In particular, current interventional trials are targeting a reduction
      in corticosteroid exposure in an effort to make induction and maintenance
      regimens safer. 

PMID- 25583295
TI  - Novel solid dispersions of benznidazole: preparation, dissolution profile and
      biological evaluation as alternative antichagasic drug delivery system.
AB  - Solid dispersions (SD) of benznidazole (BNZ) in sodium deoxycholate (NaDC) or low
      substituted hydroxypropylcellulose (L-HPC) were developed by freeze-drying
      process to improve the solubility of this low water-soluble drug and
      consequently, its trypanocidal activity. Although the dissolution studies showed
      a progressive decrease in the release rate of BNZ when formulated in the presence
      of NaDC, the increase in the surfactant concentration resulted in a better
      trypanocidal profile on epimastigotes, as well as in an enhancement of the
      unspecific cytotoxicity. However, such an effect was not so evident on
      amastigotes and in vivo (blood-trypomastigotes), where high concentrations of
      surfactant (BNZ:NaDC >= 1:6) experimented a loss of activity, correlating this
      fact with the minor cession of BNZ these formulations accomplished in acidic
      locations (i.e., dissolution test medium). According to the in vitro results, we
      reformulated the promising SD-1:3 (IC50 epimastigotes = 33.92 +/- 6.41 uM, IC50
      amastigotes = 0.40 +/- 0.05 uM and LC50 = 183.87 +/- 12.30 uM) replacing NaDC by
      L-HPC, which achieved the fastest dissolution profile. This fact, together with
      the safety this carrier ensures (LC50 > 256 uM), prompted us to evaluate the
      cellulose SD in vivo, improving the effectiveness of its NaDC equivalent (%AUPC =
      96.65% and 91.93%, respectively). The results compiled in the present work
      suggest these solid dispersions as alternative drug delivery systems to improve
      the limited chemotherapy of Chagas disease.

PMID- 25583296
TI  - Predicting the number of emergency department presentations in Western Australia:
      a population-based time series analysis.
AB  - OBJECTIVE: To predict the number of ED presentations in Western Australia (WA) in
      the next 5 years, stratified by place of treatment, age, triage and disposition.
      METHODS: We conducted a population-based time series analysis of 7 year monthly
      WA statewide ED presentation data from the financial years 2006/07 to 2012/13
      using univariate autoregressive integrated moving average (ARIMA) and
      multivariate vector-ARIMA techniques. RESULTS: ED presentations in WA were
      predicted to increase from 990,342 in 2012/13 to 1,250,991 (95% CI: 982,265
      1,519,718) in 2017/18, an increase of 260,649 (or 26.3%). The majority of this
      increase would occur in metropolitan WA (84.2%). The compound annual growth rate
      (CAGR) in metropolitan WA in the next 5 years was predicted to be 6.5% compared
      with 2.0% in the non-metropolitan area. The greatest growth in metropolitan WA
      would be in ages 65 and over (CAGR, 6.9%), triage categories 2 and 3 (8.3% and
      7.7%, respectively) and admitted (9.8%) cohorts. The only predicted decrease was
      triage category 5 (-5.3%). CONCLUSIONS: ED demand in WA will exceed population
      growth. The highest growth will be in patients with complex care needs. An
      integrated system-wide strategy is urgently required to ensure access, quality
      and sustainability of the health system.

PMID- 25583297
TI  - Immune checkpoint modulation: rational design of combination strategies.
AB  - Immune recognition and elimination of malignant cells require a series of steps
      orchestrated by the innate and the adaptive arms of the immune system. The
      majority of tumors have evolved mechanisms that allow for successful evasion of
      these immune responses. Recognition of these evasive processes led to the
      development of immunotherapeutic antibodies targeting the co-stimulatory and co
      inhibitory receptors on T cells, with the goal of enhancement of T cell
      activation or reversal of tumor-induced T cell inhibition. Several of these
      agents, such as antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4)
      and programmed death receptor 1 (PD-1) have already demonstrated significant
      promise in clinical trials. Clinical benefit of these antibodies as single
      agents, however, has been limited to a subset of patients and has not been
      observed in all tumor types. These limitations call for the development of
      rational combination strategies aiming to extend therapeutic benefit to a broader
      range of patients. These include: 1) modalities that enhance antigen
      presentation, such as radiation, cryotherapy, chemotherapy, targeted agents,
      vaccines, toll-like receptor (TLR) agonists, type I interferon, and oncolytic
      viruses; 2) additional agents aiming to reverse T cell dysfunction, such as other
      immune checkpoint inhibitors; and 3) agents targeting other immune inhibitory
      mechanisms, such as inhibitors of indoleamine dioxygenase (IDO), regulatory T
      cells, and myeloid-derived suppressor cells (MDSCs). It is becoming increasingly
      evident that the efficacy of specific combinations will likely not be universal
      and that the choice of a treatment modality may need to be tailored to fit the
      needs of each individual patient.

PMID- 25583292
TI  - Extracorporeal Treatment for Lithium Poisoning: Systematic Review and
      Recommendations from the EXTRIP Workgroup.
AB  - The Extracorporeal Treatments in Poisoning Workgroup was created to provide
      evidence-based recommendations on the use of extracorporeal treatments in
      poisoning. Here, the EXTRIP workgroup presents its recommendations for lithium
      poisoning. After a systematic literature search, clinical and toxicokinetic data
      were extracted and summarized following a predetermined format. The entire
      workgroup voted through a two-round modified Delphi method to reach a consensus
      on voting statements. A RAND/UCLA Appropriateness Method was used to quantify
      disagreement, and anonymous votes were compiled and discussed in person. A second
      vote was conducted to determine the final workgroup recommendations. In total,
      166 articles met inclusion criteria, which were mostly case reports, yielding a
      very low quality of evidence for all recommendations. A total of 418 patients
      were reviewed, 228 of which allowed extraction of patient-level data. The
      workgroup concluded that lithium is dialyzable (Level of evidence=A) and made the
      following recommendations: Extracorporeal treatment is recommended in severe
      lithium poisoning (1D). Extracorporeal treatment is recommended if kidney
      function is impaired and the [Li(+)] is >4.0 mEq/L, or in the presence of a
      decreased level of consciousness, seizures, or life-threatening dysrhythmias
      irrespective of the [Li(+)] (1D). Extracorporeal treatment is suggested if the
      [Li(+)] is >5.0 mEq/L, significant confusion is present, or the expected time to
      reduce the [Li(+)] to <1.0 mEq/L is >36 hours (2D). Extracorporeal treatment
      should be continued until clinical improvement is apparent or [Li(+)] is <1.0
      mEq/L (1D). Extracorporeal treatments should be continued for a minimum of 6
      hours if the [Li(+)] is not readily measurable (1D). Hemodialysis is the
      preferred extracorporeal treatment (1D), but continuous RRT is an acceptable
      alternative (1D). The workgroup supported the use of extracorporeal treatment in
      severe lithium poisoning. Clinical decisions on when to use extracorporeal
      treatment should take into account the [Li(+)], kidney function, pattern of
      lithium toxicity, patient's clinical status, and availability of extracorporeal
      treatments. 

PMID- 25583299
TI  - Biologically inspired dynamic material systems.
AB  - Numerous examples of material systems that dynamically interact with and adapt to
      the surrounding environment are found in nature, from hair-based mechanoreceptors
      in animals to self-shaping seed dispersal units in plants to remodeling bone in
      vertebrates. Inspired by such fascinating biological structures, a wide range of
      synthetic material systems have been created to replicate the design concepts of
      dynamic natural architectures. Examples of biological structures and their man
      made counterparts are herein revisited to illustrate how dynamic and adaptive
      responses emerge from the intimate microscale combination of building blocks with
      intrinsic nanoscale properties. By using top-down photolithographic methods and
      bottom-up assembly approaches, biologically inspired dynamic material systems
      have been created 1) to sense liquid flow with hair-inspired
      microelectromechanical systems, 2) to autonomously change shape by utilizing
      plantlike heterogeneous architectures, 3) to homeostatically influence the
      surrounding environment through self-regulating adaptive surfaces, and 4) to
      spatially concentrate chemical species by using synthetic microcompartments. The
      ever-increasing complexity and remarkable functionalities of such synthetic
      systems offer an encouraging perspective to the rich set of dynamic and adaptive
      properties that can potentially be implemented in future man-made material
      systems. 

PMID- 25583298
TI  - A long-recommended but seldom-used method of analysis for fall injuries found a
      unique pattern of risk factors in the youngest-old.
AB  - BACKGROUND: Few studies on fall risk factors use long-recommended methods for
      analysis of recurrent events. Previous falls are the biggest risk factor for
      future falls, but few fall studies focus on the youngest-old. AIMS: This study's
      objective was to apply Cox regression for recurrent events to identify factors
      associated with injurious falls in the youngest-old. METHODS: Participants were
      community-dwelling residents of southern Sweden (n = 1,133), aged 59-67 at
      baseline (median 61.2), from the youngest cohorts of the larger Good Aging in
      Skane (GAS) study. Exposure variable data were collected from baseline study
      visits and medical records. Injurious falls, defined as emergency, inpatient, or
      specialist visits associated with ICD-10 fall codes during the follow-up period
      (2001-2011), were gathered from national and regional registries. Analysis was
      conducted using time to event Cox Regression for recurrent events. RESULTS: A
      majority (77.1 %) of injurious falls caused serious injuries such as fractures
      and open wounds. Exposure to nervous system medications [hazard ratio (HR) 1.40,
      95 % confidence interval (CI) 1.03-1.89], central nervous system disease (HR
      1.79, CI 1.18-2.70), and previous injurious fall(s) (HR 2.00, CI 1.50-2.68) were
      associated with increased hazard of injurious fall. CONCLUSIONS: Regression for
      recurrent events is feasible with typical falls' study data. The association of
      certain exposures with increased hazard of injurious falls begins earlier than
      previously studied. Different patterns of risk factors by age can provide insight
      into the progression of frailty. Tailored fall prevention screening and
      intervention may be of value in populations younger than those traditionally
      screened.

PMID- 25583300
TI  - Single-tube methylation-specific duplex-PCR assay for rapid and accurate
      diagnosis of Fragile X Mental Retardation 1-related disorders.
AB  - AIM: Molecular diagnosis of fragile X syndrome demands assessment of fragile X
      mental retardation 1 (FMR1) CGG repeat size and methylation status, while
      predicting disease transmission risk requires determination of AGG interruption
      pattern. There is currently no single assay that provides all three categories of
      information. We describe a single-tube methylation-specific triplet-primed PCR
      assay for concurrently assessing methylation state, repeat size and structure of
      CGG repeat(s). METHODS: Differentially labeled primers specific for methylated
      and unmethylated FMR1 alleles were used to amplify bisulfite-modified DNA,
      followed by capillary electrophoresis. Twenty-four reference DNAs and 107 patient
      samples were analyzed to evaluate assay performance. RESULTS: Repeat size, AGG
      interruption pattern and methylation state were correctly identified in all
      tested samples. The assay also detected skewed X-inactivation when present in
      females, and somatic mosaicism in fragile X males. CONCLUSION: When used in a
      molecular diagnostic setting, this novel assay could significantly minimize the
      need to reflex patient samples for Southern analysis.

PMID- 25583301
TI  - Continuous production of cyclodextrins in an ultrafiltration membrane reactor,
      catalyzed by cyclodextrin glycosyltransferase from Bacillus circulans DF 9R.
AB  - Cyclodextrins (CDs) are cyclic oligosaccharides of wide industrial application,
      whose synthesis is catalyzed by Cyclodextrin glycosyltransferase (CGTase) from
      starch. Here, CDs were produced using CGTase from Bacillus circulans DF 9R in
      continuous process and an ultrafiltration membrane reactor. The batch process was
      conducted as a control. This method allowed increasing the yield from 40 to 55.6%
      and the productivity from 26.1 to 99.5 mg of CD per unit of enzyme. The method
      also allowed obtaining a high-purity product. The flow rate remained at 50% of
      its initial value after 24 h of process, improving the results described in the
      literature for starch hydrolysis processes. CGTase remained active throughout the
      process, which could be explained by the protective effect of the substrate and
      reaction products on CGTase stability. In addition, batch processes were
      developed using starches from different sources. We concluded that any of the
      starches studied could be used as substrate for CD production with similar yields
      and product specificity.

PMID- 25583302
TI  - Reframing HIV care: putting people at the centre of antiretroviral delivery.
AB  - The delivery of HIV care in the initial rapid scale-up of HIV care and treatment
      was based on existing clinic-based models, which are common in highly resourced
      settings and largely undifferentiated for individual needs. A new framework for
      treatment based on variable intensities of care tailored to the specific needs of
      different groups of individuals across the cascade of care is proposed here.
      Service intensity is characterised by four delivery components: (i) types of
      services delivered, (ii) location of service delivery, (iii) provider of health
      services and (iv) frequency of health services. How these components are
      developed into a service delivery framework will vary across countries and
      populations, with the intention being to improve acceptability and care outcomes.
      The goal of getting more people on treatment before they become ill will
      necessitate innovative models of delivering both testing and care. As HIV
      programmes expand treatment eligibility, many people entering care will not be
      'patients' but healthy, active and productive members of society. To take the
      framework to scale, it will be important to: (i) define which individuals can be
      served by an alternative delivery framework; (ii) strengthen health systems that
      support decentralisation, integration and task shifting; (iii) make the supply
      chain more robust; and (iv) invest in data systems for patient tracking and for
      programme monitoring and evaluation.

PMID- 25583303
TI  - Development of novel docetaxel phospholipid nanoparticles for intravenous
      administration: quality by design approach.
AB  - The objective of this study was to develop novel docetaxel phospholipid
      nanoparticles (NDPNs) for intravenous administration. Modified solvent diffusion
      evaporation method was adopted in the NDPN preparation. Central composite design
      (CCD) was employed in the optimization of the critical formulation factor (drug
      content) and process variable (stirring rate) to obtain NDPNs with 215.53 +/- 1.9
      nm particle size, 0.329 +/- 0.02 polydispersity index (PDI), and 75.41 +/- 4.81%
      entrapment efficiency. The morphological examination by transmission electron
      microscopy revealed spherical structure composed of a drug core stabilized within
      the phospholipid shell. Enhanced cell uptake of coumarin-6-loaded phospholipid
      nanoparticles by MCF-7 cell line indicated NDPN-efficient cell uptake. In vitro
      hemolysis test confirmed the safety of the phospholipid nanoparticles. NDPNs
      exhibited increased area under the curve (AUC) and mean residence time (MRT) by
      3.0- and 3.3-fold, respectively, in comparison with the existing docetaxel
      parenteral formulation (Taxotere(r)), indicating a potential for sustained
      action. Thus, the novel NDPNs exhibit an ability to be an intravenous docetaxel
      formulation with enhanced uptake, decreased toxicity, and prolonged activity. 

PMID- 25583304
TI  - The effect of microcrystalline cellulose crystallinity on the hydrophilic
      property of tablets and the hydrolysis of acetylsalicylic acid as active
      pharmaceutical ingredient inside tablets.
AB  - The crystal structures of active pharmaceutical ingredients and excipients should
      be strictly controlled because they influence pharmaceutical properties of
      products which cause the change in the quality or the bioavailability of the
      products. In this study, we investigated the effects of microcrystalline
      cellulose (MCC) crystallinity on the hydrophilic properties of tablets and the
      hydrolysis of active pharmaceutical ingredient, acetylsalicylic acid (ASA),
      inside tablets by using tablets containing 20% MCC as an excipient. Different
      levels of grinding were applied to MCC prior to tablet formulation, to
      intentionally cause structural variation in the MCC. The water penetration and
      moisture absorbability of the tablets increased with decreasing the crystallinity
      of MCC through higher level of grinding. More importantly, the hydrolysis of ASA
      inside tablets was also accelerated. These results indicate that the
      crystallinity of MCC has crucial effects on the pharmaceutical properties of
      tablets even when the tablets contain a relatively small amount of MCC.
      Therefore, controlling the crystal structure of excipients is important for
      controlling product qualities. 

PMID- 25583305
TI  - Calorimetric quantification of linked equilibria in cyclodextrin/lipid/detergent
      mixtures for membrane-protein reconstitution.
AB  - Reconstitution from detergent micelles into lipid bilayer membranes is a
      prerequisite for many in vitro studies on purified membrane proteins.
      Complexation by cyclodextrins offers an efficient and tightly controllable way of
      removing detergents for membrane-protein reconstitution, since cyclodextrins
      sequester detergents at defined stoichiometries and with tuneable affinities. To
      fully exploit the potential advantages of cyclodextrin for membrane-protein
      reconstitution, we establish a quantitative model for predicting the
      supramolecular transition from mixed micelles to vesicles during cyclodextrin
      mediated detergent extraction. The model is based on a set of linked equilibria
      among all pseudophases present in the course of the reconstitution process.
      Various isothermal titration-calorimetric protocols are used for quantifying a
      detergent's self-association as well as its colloidal and stoichiometric
      interactions with lipid and cyclodextrin, respectively. The detergent's critical
      micellar concentration, the phase boundaries in the lipid/detergent phase
      diagram, and the dissociation constant of the cyclodextrin/detergent complex thus
      obtained provide all thermodynamic parameters necessary for a quantitative
      prediction of the transition from micelles to bilayer membranes during
      cyclodextrin-driven reconstitution. This is exemplified and validated by stepwise
      complexation of the detergent lauryldimethylamine N-oxide in mixtures with the
      phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine upon titration with
      2-hydroxypropyl-beta-cyclodextrin, both in the presence and in the absence of the
      membrane protein Mistic. The calorimetric approach presented herein
      quantitatively predicts the onset and completion of the reconstitution process,
      thus obviating cumbersome trial-and-error efforts and facilitating the rational
      optimisation of reconstitution protocols, and can be adapted to different
      cyclodextrin/lipid/detergent combinations. 

PMID- 25583306
TI  - Topical N-acetylcysteine improves wound healing comparable to dexpanthenol: an
      experimental study.
AB  - In this study, we aimed to compare the effects of dexpanthenol and N
      acetylcysteine on wound healing. The wound healing process is a multifaceted
      sequence of activities associated with tissue restoration process. A number of
      investigations and clinical studies have been performed to determine new
      approaches for the improvement of wound healing. A total of 30 rats were divided
      into 3 equal groups. A linear 2-cm incision was made in the rats' skin. No
      treatment was administered in the first (control) group. Dexpanthenol cream was
      administered to the rats in the second group and 3% N-acetylcysteine cream was
      administered to the rats in the third group. The wound areas of all of the rats
      were measured on certain days. On the 21st day, all wounds were excised and
      histologically evaluated. The epithelialization and granulation rates between the
      groups were revealed to be similar in microscopic evaluations. Although the
      fibrosis was remarkable in the control group as compared with the other groups,
      it was similar in N-acetylcysteine and dexpanthenol groups. Angiogenesis rate was
      remarkable in the N-acetylcysteine group compared with the others. In multiple
      comparison analysis, Dexpanthenol and N-acetylcysteine groups had similar results
      in terms of wound healing rates (P < 0.05), which were both higher than in the
      control group (P > 0.05). The efficacy of N-acetylcysteine in wound healing is
      comparable to dexpanthenol, and both substances can be used to improve wound
      healing. 

PMID- 25583307
TI  - Vasopressors for the treatment of maternal hypotension following spinal
      anaesthesia for elective caesarean section: past, present and future.

PMID- 25583310
TI  - [Vertigo and syncope: two symptoms, various diagnoses].

PMID- 25583309
TI  - Ultraviolet and photosynthetically active radiation can both induce
      photoprotective capacity allowing barley to overcome high radiation stress.
AB  - The main objective of this study was to determine the effects of acclimation to
      ultraviolet (UV) and photosynthetically active radiation (PAR) on photoprotective
      mechanisms in barley leaves. Barley plants were acclimated for 7 days under three
      combinations of high or low UV and PAR treatments ([UV-PAR-], [UV-PAR+],
      [UV+PAR+]). Subsequently, plants were exposed to short-term high radiation stress
      (HRS; defined by high intensities of PAR - 1000 MUmol m(-2) s(-1), UV-A - 10 W m(
      2) and UV-B 2 W m(-2) for 4 h), to test their photoprotective capacity. The
      barley variety sensitive to photooxidative stress (Barke) had low constitutive
      flavonoid content compared to the resistant variety (Bonus) under low UV and PAR
      intensities. The accumulation of lutonarin and 3-feruloylquinic acid, but not of
      saponarin, was greatly enhanced by high PAR and further increased by UV exposure.
      Acclimation of plants to both high UV and PAR intensities also increased the
      total pool of xanthophyll-cycle pigments (VAZ). Subsequent exposure to HRS
      revealed that prior acclimation to UV and PAR was able to ameliorate the negative
      consequences of HRS on photosynthesis. Both total contents of epidermal flavonols
      and the total pool of VAZ were closely correlated with small reductions in light
      saturated CO2 assimilation rate and maximum quantum yield of photosystem II
      photochemistry caused by HRS. Based on these results, we conclude that growth
      under high PAR can substantially increase the photoprotective capacity of barley
      plants compared with plants grown under low PAR. However, additional UV radiation
      is necessary to fully induce photoprotective mechanisms in the variety Barke.
      This study demonstrates that UV-exposure can lead to enhanced photoprotective
      capacity and can contribute to the induction of tolerance to high radiation
      stress in barley.

PMID- 25583312
TI  - Composite nanoplatelets combining soft-magnetic iron oxide with hard-magnetic
      barium hexaferrite.
AB  - By coupling two different magnetic materials inside a single composite
      nanoparticle, the shape of the magnetic hysteresis can be engineered to meet the
      requirements of specific applications. Sandwich-like composite nanoparticles
      composed of a hard-magnetic Ba-hexaferrite (BaFe12O19) platelet core in between
      two soft-magnetic spinel iron oxide maghemite (gamma-Fe2O3) layers were
      synthesized using a new, simple and inexpensive method based on the co
      precipitation of Fe(3+)/Fe(2+) ions in an aqueous suspension of hexaferrite core
      nanoparticles. The required close control of the supersaturation of the
      precipitating species was enabled by the controlled release of the Fe(3+) ions
      from the nitrate complex with urea ([Fe((H2N)2C=O)6](NO3)3) and by using Mg(OH)2
      as a solid precipitating agent. The platelet Ba-hexaferrite nanoparticles of
      different sizes were used as the cores. The controlled coating resulted in an
      exclusively heterogeneous nucleation and the topotactic growth of the spinel
      layers on both basal surfaces of the larger hexaferrite nanoplatelets. The direct
      magnetic coupling between the core and the shell resulted in a strong increase of
      the energy product |BH|max. Ultrafine core nanoparticles reacted with the
      precipitating species and homogeneous product nanoparticles were formed, which
      differ in terms of the structure and composition compared to any other compound
      in the BaO-Fe2O3 system.

PMID- 25583311
TI  - [Weight loss and chronic diarrhea in a 54-year-old man with HIV infection].
AB  - A 54-year-old man presented with a 6-week history of chronic diarrhea and weight
      loss of 11 kg after returning from a holiday in Thailand. The patient had a 9
      year history of an untreated HIV infection. Despite treatment of a culture-proven
      Shigella enteritis and strongyloidiasis the symptoms persisted. Finally,
      cytomegalovirus (CMV) colitis was diagnosed by colonoscopy. The patient recovered
      completely after starting antiretroviral and valganciclovir treatment. An
      additional opportunistic infection with multiresistant pulmonary tuberculosis was
      diagnosed.

PMID- 25583313
TI  - Raman spectroscopic studies on screening of myopathies.
AB  - Myopathies are among the major causes of mortality in the world. There is no
      complete cure for this heterogeneous group of diseases, but a sensitive,
      specific, and fast diagnostic tool may improve therapy effectiveness. In this
      study, Raman spectroscopy is applied to discriminate between muscle mutants in
      Drosophila on the basis of associated changes at the molecular level. Raman
      spectra were collected from indirect flight muscles of mutants, upheld(1)
      (up(1)), heldup(2) (hdp(2)), myosin heavy chain(7) (Mhc(7)), actin88F(KM88)
      (Act88F(KM88)), upheld(101) (up(101)), and Canton-S (CS) control group, for both
      2 and 12 days old flies. Difference spectra (mutant minus control) of all the
      mutants showed an increase in nucleic acid and beta-sheet and/or random coil
      protein content along with a decrease in alpha-helix protein. Interestingly, the
      12th day samples of up(1) and Act88F(KM88) showed significantly higher levels of
      glycogen and carotenoids than CS. A principal components based linear
      discriminant analysis classification model was developed based on
      multidimensional Raman spectra, which classified the mutants according to their
      pathophysiology and yielded an overall accuracy of 97% and 93% for 2 and 12 days
      old flies, respectively. The up(1) and Act88F(KM88) (nemaline-myopathy) mutants
      form a group that is clearly separated in a linear discriminant plane from
      up(101) and hdp(2) (cardiomyopathy) mutants. Notably, Raman spectra from a human
      sample with nemaline-myopathy formed a cluster with the corresponding Drosophila
      mutant (up(1)). In conclusion, this is the first demonstration in which
      myopathies, despite their heterogeneity, were screened on the basis of
      biochemical differences using Raman spectroscopy. 

PMID- 25583314
TI  - Equity in breastfeeding: where do we go from here?

PMID- 25583315
TI  - Lessons learned from African American women who breastfeed.

PMID- 25583316
TI  - Cultural determinants of optimal breastfeeding practices among indigenous Mam
      Mayan women in the Western Highlands of Guatemala.
AB  - BACKGROUND: Among indigenous Mam-Mayan women, breastfeeding practices may be
      intertwined with cultural influences during the early postpartum period.
      OBJECTIVES: Our study explored whether beliefs regarding transmission of emotions
      through breast milk, the feeding of aguitas or temascal (traditional sauna) use
      were associated with achievement of the World Health Organization infant feeding
      recommendations and if these cultural practices served as moderators of the
      relationship between optimal breastfeeding practices and infant anthropometry.
      METHODS: We recruited 190 mother-infant dyads at infant age < 46 days. Data on
      breastfeeding and cultural practices were collected via questionnaire. Infant
      length, weight, and head circumference were measured and z scores were
      calculated. Multiple linear and logistic regression analyses were used to examine
      determinants of initiation of breastfeeding within 1 hour, breastfeeding
      frequency, breastfeeding exclusivity, and infant weight-for-age z score (WAZ).
      RESULTS: Mothers who delivered at the traditional midwife's house (odds ratio
      [OR] = 2.5) and those who did not believe in the transmission of susto (fright)
      through breast milk (OR = 2.4) were more likely to initiate breastfeeding within
      1 hour postpartum. Higher breastfeeding frequency was observed among mothers who
      spent more time in the temascal. Initiating early breastfeeding within 1 hour
      postpartum was the sole infant feeding practice positively associated with
      exclusive breastfeeding and WAZ. CONCLUSIONS: Our investigation in the Western
      Highlands of Guatemala has highlighted the link between cultural practices and
      beliefs during lactation, breastfeeding practices and infant growth. Public
      health practitioners need to understand how local cultural practices influence
      early initiation of breastfeeding to promote adequate infant weight.

PMID- 25583317
TI  - Yes, we can get along!

PMID- 25583318
TI  - Authors' response: A table for two (... Or three, or four).

PMID- 25583319
TI  - Getting along in Georgia: a model for IBCLC licensure.

PMID- 25583320
TI  - Authors' response: The journey to getting along in Georgia.

PMID- 25583321
TI  - Breastfeeding without birthing: mothers through adoption or surrogacy can
      breastfeed!

PMID- 25583324
TI  - A new picrotoxane sesquiterpene from the berries of Baccaurea ramiflora with
      antifungal activity against Colletotrichum gloeosporioides.
AB  - Three picrotoxane sesquiterpenes including one new glycoside and two known
      constituents, sapidolide A (2) and picrotoximaesin (3), were isolated from the
      berries of Baccaurea ramiflora. The structure of the new sesquiterpene glycoside,
      ramifloside (1), was elucidated as 2-one-6alpha-hydroxy-13-nor-11-picrotoxen
      3(15beta)-olide 10-O-beta-D-glucopyranoside on the basis of extensive
      spectroscopic analysis. Compounds 1-3 exhibited antifungal activity against
      Colletotrichum gloeosporioides with MICs of 12.5, 12.5 and 50 MUg/mL.

PMID- 25583326
TI  - Erratum: BatTool: an R package with GUI for assessing the effect of white-nose
      syndrome and other take events on Myotis spp. of bats.
AB  - [This corrects the article DOI: 10.1186/1751-0473-9-9.]. 

PMID- 25583327
TI  - Considerations about endoscopic endonasal optic nerve and orbital apex
      decompression.

PMID- 25583325
TI  - Visceral abdominal obesity is associated with an increased risk of irritable
      bowel syndrome.
AB  - OBJECTIVES: There are several studies considering obesity as the risk factor for
      various lower gastrointestinal symptoms. But the relationship between visceral
      abdominal obesity and the incidence of irritable bowel syndrome (IBS) is not
      studied yet. The aim of this study was to investigate the association between
      visceral adipose tissue (VAT) and the risk of IBS. METHODS: This is a case
      control study comparing the VAT area between subjects with IBS (IBS group) and
      controls without IBS (non IBS group), who underwent abdomen computerized
      tomography (CT) for routine health checkup from January 2012 to August 2013 in a
      health promotion center. A telephone survey was retrospectively conducted to
      diagnose IBS by Rome III criteria. The association between IBS and abdominal
      obesity was evaluated by measuring VAT, subcutaneous adipose tissue (SAT),
      VAT/SAT ratio, body mass index (BMI) and waist circumference (WC). RESULTS: The
      prevalence of IBS was 19.9% (67/336) among all enrolled subjects. In the
      univariate analysis, VAT area, VAT/SAT ratio, waist circumference, the presence
      of reflux esophagitis and the ratio of females were significantly higher in the
      IBS group than in the non IBS group. However, a higher BMI or a higher SAT area
      is not associated with an increased risk of IBS. In the multivariate analysis, a
      higher VAT area (odds ratio (OR)=9.42, 95% confidence interval (CI): 2.90-30.64,
      highest tertile vs. lowest tertile, P=0.001), VAT/SAT ratio (OR=10.15, 95% CI:
      3.05-33.58, highest tertile vs. lowest tertile, P=0.001) and waist circumference
      (OR=7.81, 95% CI: 2.13-28.66, highest tertile vs. lowest tertile, P=0.002) were
      independently associated with a risk of IBS. Only in the IBS-D group, not in the
      IBS-C, visceral adiposity was associated with an increased risk of IBS.
      CONCLUSIONS: Visceral adiposity measured by VAT, VAT/SAT, and waist circumference
      is associated with an increased risk of IBS, especially of IBS-D. However,
      neither SAT nor BMI are associated with an increased risk of IBS.

PMID- 25583328
TI  - Attenuation of microRNA-16 derepresses the cyclins D1, D2 and E1 to provoke
      cardiomyocyte hypertrophy.
AB  - Cyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte
      hypertrophy. MicroRNAs (miRNAs), the endogenous small non-coding RNAs, were
      recognized to play significant roles in cardiac hypertrophy. But, it remains
      unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac
      hypertrophy. This study investigates the potential role of microRNA-16 (miR-16)
      in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy. An animal model
      of hypertrophy was established in a rat with abdominal aortic constriction (AAC),
      and in a mouse with transverse aortic constriction (TAC) and in a mouse with
      subcutaneous injection of phenylephrine (PE) respectively. In addition, a cell
      model of hypertrophy was also achieved based on PE-promoted neonatal rat
      ventricular cardiomyocyte and based on Ang-II-induced neonatal mouse ventricular
      cardiomyocyte respectively. We demonstrated that miR-16 expression was markedly
      decreased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats and
      mice. Overexpression of miR-16 suppressed rat cardiac hypertrophy and
      hypertrophic phenotype of cultured cardiomyocytes, and inhibition of miR-16
      induced a hypertrophic phenotype in cardiomyocytes. Expressions of cyclins D1, D2
      and E1, and the phosphorylated pRb were increased in hypertrophic myocardium and
      hypertrophic cardiomyocytes, but could be reversed by enforced expression of miR
      16. Cyclins D1, D2 and E1, not pRb, were further validated to be modulated post
      transcriptionally by miR-16. In addition, the signal transducer and activator of
      transcription-3 and c-Myc were activated during myocardial hypertrophy, and
      inhibitions of them prevented miR-16 attenuation. Therefore, attenuation of miR
      16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2 and E1,
      and activating cyclin/Rb pathway, revealing that miR-16 might be a target to
      manage cardiac hypertrophy. 

PMID- 25583330
TI  - [On 'Emergent strains of rifampicin-resistant Mycobacterium tuberculosis complex
      and susceptibility to isoniazid'. Author's reply].

PMID- 25583331
TI  - [Proteomics in infectious diseases].
AB  - Infectious diseases have a high incidence in the population, causing a major
      impact on global health. In vitro culture of microorganisms is the first
      technique applied for infection diagnosis which is laborious and time consuming.
      In recent decades, efforts have been focused on the applicability of "Omics"
      sciences, highlighting the progress provided by proteomic techniques in the field
      of infectious diseases. This review describes the management, processing and
      analysis of biological samples for proteomic research.

PMID- 25583329
TI  - Motor neuron cell-nonautonomous rescue of spinal muscular atrophy phenotypes in
      mild and severe transgenic mouse models.
AB  - Survival of motor neuron (SMN) deficiency causes spinal muscular atrophy (SMA),
      but the pathogenesis mechanisms remain elusive. Restoring SMN in motor neurons
      only partially rescues SMA in mouse models, although it is thought to be
      therapeutically essential. Here, we address the relative importance of SMN
      restoration in the central nervous system (CNS) versus peripheral tissues in
      mouse models using a therapeutic splice-switching antisense oligonucleotide to
      restore SMN and a complementary decoy oligonucleotide to neutralize its effects
      in the CNS. Increasing SMN exclusively in peripheral tissues completely rescued
      necrosis in mild SMA mice and robustly extended survival in severe SMA mice, with
      significant improvements in vulnerable tissues and motor function. Our data
      demonstrate a critical role of peripheral pathology in the mortality of SMA mice
      and indicate that peripheral SMN restoration compensates for its deficiency in
      the CNS and preserves motor neurons. Thus, SMA is not a cell-autonomous defect of
      motor neurons in SMA mice. 

PMID- 25583332
TI  - Microbiota and metabolites of aged bottled gueuze beers converge to the same
      composition.
AB  - Gueuze beers are prepared by mixing young and old lambic beers and are bottle
      refermented spontaneously for aging. The present study analyzed the microbiota
      and metabolites present in gueuze beers that were aged between a few months and
      up to 17 years. Yeasts were cultivated from all beers sampled, but bacteria could
      not be grown from beers older than 5 years. Lactic acid and ethyl lactate
      concentrations increased steadily during aging, whereas ethanol concentrations
      remained constant. The concentrations of isoamyl acetate and ethyl decanoate
      decreased during the aging process. Hence, ethyl lactate and ethyl decanoate can
      be considered as positive and negative gueuze beer-aging metabolite biomarkers,
      respectively. Nevertheless, considerable bottle-to-bottle variation in the
      metabolite profiles was found, which hindered the generalization of the effects
      seen during the aging of the gueuze beers examined, but which illustrated the
      unique character of the lambic beers. The present results further indicate that
      gueuze beers are preferably aged for less than 10 years. 

PMID- 25583333
TI  - Effect of lipolytic activity of Candida adriatica, Candida diddensiae and
      Yamadazyma terventina on the acidity of extra-virgin olive oil with a different
      polyphenol and water content.
AB  - Previous microbiological research demonstrated the presence of a rich micro-flora
      composed mainly of yeasts in the suspended fraction of freshly produced olive
      oil. Some of the yeasts are considered harmful as they can damage the quality of
      the olive oil through the hydrolysis of the triacylglycerols. Present research
      has demonstrated that the lipolytic activity of some lipase-producer strains
      belonging to a yeast species called Candida adriatica, Candida diddensiae and
      Yamadazyma terventina can be modulated by the water and the polyphenol content of
      olive oil. Laboratory tests highlighted a substantial increase in free fatty acid
      in the inoculated olive oil characterized by high water content and low
      polyphenol concentration. The acidity of the olive oil samples containing 0.06%
      and 0.31% of water increased significantly by 33% in the lipase-producer yeast
      strains tested during a period of 2 weeks of incubation at 30  degrees C. All
      other yeasts showed strong lipolytic activity in the presence of 1.31% of water -
      the only exception to this was the C. adriatica 1985 strain. The phenolic
      compounds typical of olive oil represent another important factor able to
      condition the viability and the lipolytic activity of the lipase-producer yeasts.
      From the tests performed on the olive oil characterized by an increasing content
      of total polyphenols equal to 84, 150 and 510 mg per kg of oil, the percentage of
      the lipase-producer yeasts able to hydrolyse the triacylglycerols was
      respectively 100%, 67% and 11%. 

PMID- 25583334
TI  - Occurrence, molecular characterization, and antimicrobial susceptibility of
      Aeromonas spp. in marine species of shrimps cultured at inland low salinity
      ponds.
AB  - We aimed to document the risk of Aeromonas spp. in marine shrimp species cultured
      in inland low salinity ponds in Thailand. In 14 of 18 shrimp samples retrieved
      from inland grow-up ponds, Aeromonas spp. were detected at ranges from 4667 to
      1,500,000 CFU/g body weight. The phylogenetic tree constructed with the gyrB and
      cpn60 concatenated sequences indicated that the 87 isolates consisted of
      Aeromonas veronii (70%), Aeromonas aquariorum (18%), Aeromonas caviae (7%),
      Aeromonas jandaei (2%), and Aeromonas schubertii (2%). The potential virulence of
      the isolates was examined by phenotypic and PCR assays. Hemolytic activity and
      the extracellular activity of lipase, DNase, and gelatinase were observed in most
      isolates (94-99%). PCR revealed the presence of 9 genes related to virulence in
      the 87 isolates: act (75%), aer (74%), alt (30%), ast (1%), ascV (34%), aexT
      (24%), fla (92%), ela (34%), and lip (24%). The susceptibility profiles to 14
      antimicrobial agents of isolates were typical for the genus, but resistance to
      cefotaxime, a third-generation cephalosporin, and imipenem were found in two A.
      aquariorum and in three A. veronii isolates, respectively. These resistances were
      confirmed by determining minimum inhibitory concentrations. Our results indicate
      that the microbiological risk posed by Aeromonas should be considered for marine
      shrimp species that are cultured in low-salinity ponds. These shrimps may also be
      a vehicle for the transfer of different genotypes of Aeromonas and antibiotic
      resistant determinants to regions worldwide through trade. 

PMID- 25583335
TI  - Rapid identification and classification of Campylobacter spp. using laser optical
      scattering technology.
AB  - Campylobacter jejuni and Campylobacter coli are the two important species
      responsible for most of the Campylobacter infections in humans. Reliable
      isolation and detection of Campylobacter spp. from food samples are challenging
      due to the interferences from complex food substances and the fastidious growth
      requirements of this organism. In this study, a novel biosensor-based detection
      called BARDOT (BActerial Rapid Detection using Optical scattering Technology) was
      developed for high-throughput screening of Campylobacter colonies grown on an
      agar plate without disrupting the intact colonies. Image pattern characterization
      and principal component analysis (PCA) of 6909 bacterial colonies showed that the
      light scatter patterns of C. jejuni and C. coli were strikingly different from
      those of Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes.
      Examination of a mixed culture of these microorganisms revealed 85% (34/40)
      accuracy in differentiating Campylobacter from the other three major foodborne
      pathogens based on the similarity to the scatter patterns in an established
      library. The application of BARDOT in real food has been addressed through the
      analysis of Campylobacter spiked ground chicken and naturally contaminated fresh
      chicken pieces. Combined with real-time PCR verification, BARDOT was able to
      identify Campylobacter isolates from retail chicken. Moreover, applying passive
      filtration to food samples facilitated the isolation of pure Campylobacter
      colonies and therefore overcame the interference of the food matrix on BARDOT
      analysis. 

PMID- 25583336
TI  - Application of Lactobacillus amylovorus DSM19280 in gluten-free sourdough bread
      to improve the microbial shelf life.
AB  - The present study investigated the antifungal activity of Lactobacillus
      amylovorus DSM19280 as a starter culture for gluten-free quinoa sourdough bread
      under pilot-plant conditions to extend the microbial shelf life. Challenge tests
      against environmental moulds were conducted and a negative control with non
      antifungal strain, L. amylovorus DSM20531(T), as well as a chemically acidified
      and a non-acidified control were included. Organic acid production, antifungal
      metabolites, carbohydrates changes during fermentation and bread quality were
      compared to wheat counterparts. The application of quinoa sourdough fermented
      with the antifungal L. amylovorus DSM19280 extended the mould free shelf life by
      4 days compared to the non-acidified control. No significant difference in lactic
      acid production was found between the lactobacilli strains. HPLC-UV/DAD was used
      to quantify antifungal compounds. The concentration of 4-hydroxyphenyllactic
      acid, phloretic acid, 3-phenyllactic acid and hydroferulic acid were
      significantly higher (P < 0.01) in the quinoa sourdough fermented with the
      antifungal L. amylovorus DSM19280 when compared to the non-antifungal strain,
      thus indicating their contribution to the antifungal activity. Evaluation of
      bread characteristics such as specific volume or crumb hardness, revealed that
      the addition of L. amylovorus fermented sourdough also improved bread quality. In
      conclusion, the combination of quinoa flour fermented with the antifungal L.
      amylovorus DSM19280 serves a great potential biopreservative ingredient to
      produce gluten-free breads with an improved nutritional value, better bread
      quality and higher safety due to an extended shelf life, and therefore meeting
      consumer needs for good quality and preservatives-free food products. 

PMID- 25583337
TI  - From field to fermentation: the origins of Lactococcus lactis and its
      domestication to the dairy environment.
AB  - Lactococcus lactis is an organism of substantial economic importance, used
      extensively in the production of fermented foods and widely held to have evolved
      from plant strains. The domestication of this organism to the milk environment is
      associated with genome reduction and gene decay, and the acquisition of specific
      genes involved in protein and lactose utilisation by horizontal gene transfer. In
      recent years, numerous studies have focused on uncovering the physiology and
      molecular biology of lactococcal strains from the wider environment for
      exploitation in the dairy industry. This in turn has facilitated comparative
      genome analysis of lactococci from different environments and provided insight
      into the natural phenotypic and genetic diversity of L. lactis. This diversity
      may be exploited in dairy fermentations to develop products with improved quality
      and sensory attributes. In this review, we discuss the classification of L.
      lactis and the problems that arise with phenotype/genotype designation. We also
      discuss the adaptation of non-dairy lactococci to milk, the traits associated
      with this adaptation and the potential application of non-dairy lactococci to
      dairy fermentations. 

PMID- 25583338
TI  - Dynamics and diversity of microbial community succession in traditional
      fermentation of Shanxi aged vinegar.
AB  - The traditional fermentation of Shanxi aged vinegar (SAV), a well-known
      traditional Chinese vinegar, generally involves the preparation of starter daqu,
      starch saccharification, alcoholic fermentation (AF) and acetic acid fermentation
      (AAF). Dynamics and diversity of microbial community succession in daqu and other
      fermentation stages were investigated by denaturing gradient gel electrophoresis
      (DGGE). Results showed that eight bacterial genera and four fungal genera were
      found in daqu. However, Staphylococcus, Saccharopolyspora, Bacillus,
      Oceanobacillus, Enterobacter, Streptomyces, Eurotium, Monascus and Pichia in daqu
      were eradicated during AF. Four bacterial genera and three fungal genera were
      found in this stage. Weissella, Lactobacillus, Streptococcus, Saccharomyces, and
      Saccharomycopsis were the dominant microorganisms in the late stage of AF. During
      AAF, four bacterial genera and four fungal genera were found. Weissella,
      Streptococcus, Klebsiella, Escherichia, and Cladosporium gradually disappeared;
      the dominant microorganisms were Acetobacter, Lactobacillus, Saccharomycopsis,
      and Alternaria in the late stage of AAF. Alpha diversity metrics showed that
      fungal diversity in daqu was greater than that in AF and AAF. By contrast,
      bacterial diversity decreased from daqu to AF and increased in the first three
      days of AAF and then decreased. Hence, these results could help understand
      dynamics of microbial community succession in continuous fermentation of
      traditional Chinese vinegars. 

PMID- 25583339
TI  - Application of an oregano oil nanoemulsion to the control of foodborne bacteria
      on fresh lettuce.
AB  - Although antimicrobial activities of plant essential oils are well documented,
      challenges remain as to their application in fresh produce due to the hydrophobic
      nature of essential oils. Oregano oil nanoemulsions were formulated with a food
      grade emulsifier and evaluated for their efficacy in inactivating the growth of
      foodborne bacteria on fresh lettuce. Lettuce was artificially inoculated with
      Listeria monocytogenes, Salmonella Typhimurium and Escherichia coli O157:H7,
      followed by a one-minute dipping in oregano oil nanoemulsions (0.05% or 0.1%).
      Samples were stored at 4  degrees C and enumerated for bacteria at fixed
      intervals (0 h, 3 h, 24 h, and 72 h). Compared to control, 0.05% nanoemulsion
      showed an up to 3.44, 2.31, and 3.05 log CFU/g reductions in L. monocytogenes, S.
      Typhimurium, and E. coli O157:H7, respectively. Up to 3.57, 3.26, and 3.35 log
      CFU/g reductions were observed on the same bacteria by the 0.1% treatment.
      Scanning Electron Microscopy (SEM) demonstrated disrupted bacterial membranes due
      to the oregano oil treatment. The data suggest that applying oregano oil
      nanoemulsions to fresh produce may be an effective antimicrobial control
      strategy. 

PMID- 25583341
TI  - Biocontrol ability and action mechanism of food-isolated yeast strains against
      Botrytis cinerea causing post-harvest bunch rot of table grape.
AB  - Strains belonging to the species Saccharomyces cerevisiae, Wickerhamomyces
      anomalus, Metschnikowia pulcherrima and Aureobasidium pullulans, isolated from
      different food sources, were tested in vitro as biocontrol agents (BCAs) against
      the post-harvest pathogenic mold Botrytis cinerea. All yeast strains demonstrated
      antifungal activity at different levels depending on species and medium. Killer
      strains of W. anomalus and S. cerevisiae showed the highest biocontrol in vitro
      activity, as demonstrated by largest inhibition halos. The competition for iron
      and the ability to form biofilm and to colonize fruit wounds were hypothesized as
      the main action mechanisms for M. pulcherrima. The production of hydrolytic
      enzymes and the ability to colonize the wounds were the most important mechanisms
      for biocontrol activity in A. pullulans and W. anomalus, which also showed high
      ability to form biofilm. The production of volatile organic compounds (VOCs) with
      in vitro and in vivo inhibitory effect on pathogen growth was observed for the
      species W. anomalus, S. cerevisiae and M. pulcherrima. Our study clearly
      indicates that multiple modes of action may explain as M. pulcherrima provide
      excellent control of postharvest botrytis bunch rot of grape. 

PMID- 25583340
TI  - Lactic acid bacteria and natural antimicrobials to improve the safety and shelf
      life of minimally processed sliced apples and lamb's lettuce.
AB  - Outbreaks of food-borne disease associated with the consumption of fresh and
      minimally processed fruits and vegetables have increased dramatically over the
      last few years. Traditional chemical sanitizers are unable to completely
      eradicate or kill the microorganisms on fresh produce. These conditions have
      stimulated research to alternative methods for increasing food safety. The use of
      protective cultures, particularly lactic acid bacteria (LAB), has been proposed
      for minimally processed products. However, the application of bioprotective
      cultures has been limited at the industrial level. From this perspective, the
      main aims of this study were to select LAB from minimally processed fruits and
      vegetables to be used as biocontrol agents and then to evaluate the effects of
      the selected strains, alone or in combination with natural antimicrobials (2-(E)
      hexenal/hexanal, 2-(E)-hexenal/citral for apples and thyme for lamb's lettuce),
      on the shelf-life and safety characteristics of minimally processed apples and
      lamb's lettuce. The results indicated that applying the Lactobacillus plantarum
      strains CIT3 and V7B3 to apples and lettuce, respectively, increased both the
      safety and shelf-life. Moreover, combining the selected strains with natural
      antimicrobials produced a further increase in the shelf-life of these products
      without detrimental effects on the organoleptic qualities. 

PMID- 25583342
TI  - Evaluation of aqueous and alcohol-based quaternary ammonium sanitizers for
      inactivating Salmonella spp., Escherichia coli O157:H7, and Listeria
      monocytogenes on peanut and pistachio shells.
AB  - This study evaluated the efficacy of aqueous (aQUAT) and isopropyl alcohol-based
      quaternary ammonium (ipQUAT) sanitizers for reducing Salmonella spp., Escherichia
      coli O157:H7, or Listeria monocytogenes populations on peanut and pistachio shell
      pieces. Inoculated nutshells were mixed with QUAT sanitizers, water, or 70%
      ethanol and enumerated immediately or after incubation at 30  degrees C for 48 h.
      None of the treatments had any immediate effect on Salmonella or E. coli O157:H7
      populations on the peanut or pistachio shells. L. monocytogenes populations
      declined immediately on the peanut and pistachio shells treated with aQUAT or
      ipQUAT. After incubation, Salmonella and E. coli O157:H7 populations increased
      significantly on the water- or aQUAT-treated peanut and pistachio shells. L.
      monocytogenes populations also increased significantly on the water- or aQUAT
      treated peanut shells, but levels did not change on the water-treated pistachio
      shells and levels were just above the limit of detection on the aQUAT-treated
      pistachio shells. After treatment with ipQUAT and 48-h incubation, Salmonella and
      E. coli O157:H7 populations decreased to or below the limit of detection on both
      shell types; L. monocytogenes populations remained at or below the limit of
      detection on both shell types. 

PMID- 25583343
TI  - Iranian wheat flours from rural and industrial mills: Exploitation of the
      chemical and technology features, and selection of autochthonous sourdough
      starters for making breads.
AB  - This study aimed at describing the main chemical and technology features of eight
      Iranian wheat flours collected from industrial and artisanal mills. Their
      suitability for bread making was investigated using autochthonous sourdough
      starters. Chemical analyses showed high concentration of fibers and ash, and
      technology aptitude for making breads. As shown through 2-DE analyses, gliadin
      and glutenin subunits were abundant and varied among the flours. According to the
      back slopping procedure, type I sourdoughs were prepared from Iranian flours, and
      lactic acid bacteria were typed and identified. Strains of Pediococcus
      pentosaceus, Weissella cibaria, Weissella confusa, and Leuconostoc citreum were
      the most abundant. Based on the kinetics of growth and acidification, quotient of
      fermentation and concentration of total free amino acids, lactic acid bacteria
      were selected and used as sourdough mixed starters for bread making. Compared to
      spontaneous fermentation, sourdoughs fermented with selected and mixed starters
      favored the increase of the concentrations of organic acids and total free amino
      acids, the most suitable quotient of fermentation, and the most intense phytase
      and antioxidant activities. Although the high concentration of fibers, selected
      and mixed starters improved the textural features of the breads. This study might
      had contribute to the exploitation of the potential of Iranian wheat flours and
      to extend the use of sourdough, showing positive technology, nutritional and,
      probably, economic repercussions. 

PMID- 25583344
TI  - Predictive model for the growth of spoilage bacteria on modified atmosphere
      packaged Atlantic salmon produced in Australia.
AB  - Most existing models for the spoilage of modified atmosphere packed Atlantic
      salmon are based on the growth of the spoilage organism Photobacterium
      phosphoreum. However, there is evidence that this organism is not the specific
      spoilage organism on salmon produced and packaged in Australia. We developed a
      predictive model for the growth of bacteria in Australian-produced Atlantic
      salmon stored under modified atmosphere conditions (30-98% carbon dioxide in
      nitrogen) at refrigeration temperatures (0-10  degrees C). As expected, both
      higher levels of carbon dioxide and lower temperatures decreased the observed
      growth rates of the total population. A Belehradek-type model for growth rate
      fitted the data best with an acceptably low root mean square error. At low
      temperatures (~0  degrees C) the growth rates in this study were similar to those
      predicted by other models but at higher temperatures (~10  degrees C) the growth
      rates were significantly lower in the current study. 

PMID- 25583345
TI  - Molecular detection of Anaplasma platys and Ehrlichia canis in dogs from Kabylie,
      Algeria.
AB  - Ehrlichia canis and Anaplasma platys are bacteria belonging to the
      Anaplasmataceae family that cause acute, self-limiting and sometimes fatal vector
      borne infections in dogs. These bacteria have been reported worldwide and are
      transmitted mainly by Rhipicephalus sanguineus. Aside from a report on E. canis
      once in 1935, no other Anaplasmataceae bacteria have been reported in Algeria to
      date. The aim of this study was to identify the microbial species implicated in
      ehrlichiosis and anaplasmosis by a molecular epidemiological survey in dogs. The
      study was carried out in Kabylie, in northeast Algeria. Sampling was performed in
      11 municipalities in the province of Tizi Ouzou and 2 municipalities in the
      province of Bejaia. Peripheral blood samples from 110 dogs were screened by qPCR,
      which is capable of identifying most Anaplasmataceae bacteria. Out of 110, a
      total of 13 samples screened positive (7/110 E. canis and 6/110 A. platys), and
      two genetic variants of A. platys and one of E. canis were identified. This is
      the first study to report the presence of A. platys in dogs from Algeria using a
      molecular investigative method. This survey was conducted in early spring. As
      tick activity can affect the prevalence of these pathogens in dogs, further
      investigations are needed to establish the year-round prevalence of these
      infections. 

PMID- 25583347
TI  - A silver-stain modification of standard histological slide preparation for use in
      anthropology analyses.
AB  - The traditional histology method typically employed by forensic anthropologists
      involves plastic embedding of undecalcified bone. The embedded sample is then cut
      by a diamond blade saw and ground to the required thickness of ~50-100 microns
      using a grinder. There are several limitations to this method: Cement lines may
      be blurred; depth-of-field artifacts may result from viewing thick sections; and
      medicolegal offices with limited budgets may not be able to invest in additional
      equipment or training for this method. A silver nitrate stain modification of the
      standard histology preparation technique of decalcified bone is presented. The
      benefits of this technique are that: Cement lines are viewed clearly; no depth-of
      field artifacts are present; and because this is a modification of the standard
      technique used by histology laboratories typically employed by medicolegal
      offices, no additional equipment or training is required. 

PMID- 25583346
TI  - The community distribution of bacteria and fungi on ancient wall paintings of the
      Mogao Grottoes.
AB  - In this study, we compared the microbial communities colonising ancient cave wall
      paintings of the Mogao Grottoes exhibiting signs of biodeterioration. Ten samples
      were collected from five different caves built during different time periods and
      analysed using culture-independent and culture-dependent methods. The clone
      library results revealed high microbial diversity, including the bacterial groups
      Firmicutes, Proteobacteria, Actinobacteria, Acidobacteria, Cyanobacteria,
      Bacteroidetes, Gemmatimonadetes, Planctomycetes, and Chloroflexi and the fungal
      groups Euascomycetes, Dothideomycetes, Eurotiomycetes, Sordariomycetes,
      Saccharomycetes, Plectomycetes, Pezizomycetes, Zygomycota, and Basidiomycota. The
      bacterial community structures differed among the samples, with no consistent
      temporal or spatial trends. However, the fungal community diversity index
      correlated with the building time of the caves independent of environmental
      factors (e.g., temperature or relative humidity). The enrichment cultures
      revealed that many culturable strains were highly resistant to various stresses
      and thus may be responsible for the damage to cave paintings in the Mogao
      Grottoes. 

PMID- 25583348
TI  - HIV transmission and related risk factors among serodiscordant couples in
      Liuzhou, China.
AB  - To evaluate the incidence and risk factors for human immunodeficiency virus (HIV)
      seroconversion of HIV-negative partners among HIV-discordant couples in Liuzhou,
      China, 1854 eligible HIV-serodiscordant couples were retrospectively identified
      through the HIV epidemiology and follow-up database from January 1, 1996 to June
      30, 2013. Cox proportional-hazards model was used to examine risk factors related
      to HIV seroconversion of negative partners. Finally, 125 HIV seroconversion
      occurred over 4963.5 person-years, resulting in an overall HIV incidence of
      2.52/100 person-years. HIV-positive partners with the last CD4 counts of 350
      cells/ul or more were significantly protected against HIV seroconversion compared
      with those CD4 counts of less than 200 cells/ul (aHR = 0.46, 95% CI: 0.27-0.81, P
      < 0.01). Men with HIV-positive wives (aHR: 1.96, 95% CI: 1.27-3.02, P < 0.01),
      HIV-positive partners who did not receive ART before their HIV-negative partners'
      seroconversion (aHR: 2.22, 95% CI, 1.41-3.51, P < 0.01) and patients reported
      intermittent condom use (aHR: 7.60, 95% CI, 4.37-13.21, P < 0.01) were associated
      with increased risk of HIV seroconversion. HIV-negative partners remain high risk
      of HIV infection in Liuzhou city. Comprehensive package of HIV prevention
      services should contribute to reduction in HIV transmission of discordant
      couples.

PMID- 25583349
TI  - Pseudo-subarachnoid hemorrhage in a patient with hypoxic encephalopathy.
AB  - The authors report an unusual case of diffuse subarachnoid hemorrhage on brain
      computed tomography (CT) scan in a patient with post-resuscitation anoxic
      encephalopathy. A 42-year-old woman suffered both respiratory and cardiac arrest,
      associated with hypoxic encephalopathy, which occurred during a visit to our
      gynecology clinic. CT examination was performed the next day, which revealed a
      hyperdensity in the basal cisterns with a diffuse cerebral edema. Lumbar puncture
      was applied for diagnosis. No yellow coloration or red cells were observed in the
      cerebrospinal fluid. Nineteen days after treatment, the CT examination revealed
      features of a subarachnoid hemorrhage with a significantly increased cerebral
      edema. The patient died two months later. This clinical case illustrates that
      hypoxic encephalopathy can mimic diffuse subarachnoid hemorrhage on CT scan. 

PMID- 25583350
TI  - Management of cardiac migration of a distal shunt catheter: the radiological
      pitfalls.
AB  - Cardiac migration is a rare complication of the ventriculoperitoneal shunt. We
      report a case of a late migration of the distal shunt into the pulmonary
      arteries. The authors underline the radiological features that suggested the
      presence of a knot. Preoperative planning and the assistance of a vascular
      surgeon were required due to the presence of a knot. 

PMID- 25583351
TI  - A binding-induced sutured toehold activation for controllable DNA strand
      displacement reactions.
AB  - A novel toehold activation strategy was developed based on hairpin
      reconfiguration which was initiated by the interaction between the hairpin and
      different environmental stimuli (Hg(2+) or ATP). Through variation of the
      concentration of environmental stimuli, it allowed the fine control of the DNA
      strand displacement rates almost 2 orders of magnitude. 

PMID- 25583352
TI  - Near total extirpation of vestibular schwannoma with salvage radiosurgery.
AB  - OBJECTIVES/HYPOTHESIS: The management of a sporadic vestibular schwannoma (VS)
      has changed with the introduction of stereotactic radiosurgery (SRS). Because
      functional outcome is important, particularly regarding the facial nerve, a
      policy of near-total surgical resection of a large-size VS has emerged,
      minimizing damage to the facial nerve. The debate remains whether the surgical
      remnant should be treated immediately or after established growth. STUDY DESIGN:
      Retrospective case series. METHODS: A consecutive cohort of 55 patients underwent
      a retrosigmoid craniotomy and near-total removal of a large-size VS at our
      university medical center between 2005 and 2011 and had a follow-up of a least 3
      years. Documented growth of the VS remnant after surgery necessitating adjuvant
      SRS was the primary outcome measure using analysis of variance. RESULTS: In 45
      patients (81.8%), a small tumor remnant was left during surgery. The mean
      preoperative tumor volume was 12.2 cm(3) (range, 1.13-50.16 cm(3)); the mean
      volume of the remnant was 0.22 cm(3) (range, 0-1.52 cm(3)). The mean
      postoperative follow-up time was 35.4 months (range, 3-76 months). Salvage SRS
      was deemed necessary in seven patients (13.0%). The size of the postoperative
      tumor remnant was a significant predictor for the necessity of postoperative
      adjuvant SRS. Normal facial nerve function (House-Brackmann [HB] I) was preserved
      in 30 patients (57.7%), 17 patients (32.7%) experienced a permanent mild facial
      nerve deficit (HB II, III), and five patients (9.6%) experienced a severe facial
      nerve deficit (HB grade IV-VI). CONCLUSIONS: Initial observation after near total
      surgical removal of VS is a feasible strategy, with only a minority requiring
      salvage radiosurgery during follow-up.

PMID- 25583353
TI  - Modeling interactions between C60 antiviral compounds and HIV protease.
AB  - Fullerenes have generated a great deal of interest in recent years, due to their
      properties and potential applications in many fields, including medicine. In this
      paper, we study an antiviral fullerene compound which may be used to treat the
      human immunodeficiency virus (HIV). We formulate a mathematical model which can
      describe the interaction energy between the C[Formula: see text] antiviral
      compounds and the HIV. In particular, this paper predicts the energy and force
      arising from the interaction between HIV active region and the antiviral molecule
      which is attached to the external surface of a fullerene C[Formula: see text].
      These interactions are calculated based on the structure of the antiviral
      molecules. Our results show that the binding of fullerene C[Formula: see text] to
      the antiviral molecules increases the efficiency of the compound to prohibit the
      activity of HIV. 

PMID- 25583355
TI  - A theoretical study on novel alkaline earth-based excess electron compounds:
      unique alkalides with considerable nonlinear optical responses.
AB  - On the basis of stable alkaline earth metal ammines, a series of M(NH3)6NaCl and
      M(NH3)6Na2 (M = Mg and Ca) excess electron compounds were theoretically
      constructed and studied by using the density functional theory. The electride or
      alkalide characteristics of these compounds are verified by their electronic
      structures, HOMOs, and small VIE values. It is worth noting that the M(NH3)6Na2
      alkalides have novel electronic structures that contain double alkali metal
      anions. As expected, all the noncentrosymmetric M(NH3)6NaCl and M(NH3)6Na2
      compounds possess considerable first hyperpolarizabilities (beta0) up to 123 050
      au, which can be attributed to low excitation energies (DeltaEs) and large
      oscillator strength (f0) of their crucial excited states. In addition, results
      reveal that the Ca(NH3)6-based species with lower DeltaEs and larger transition
      moments (DeltaMU) show larger beta0 values compared with the corresponding
      Mg(NH3)6-based ones with similar geometries. This study may be significant in
      terms of designing excess electron compounds of new-type, especially alkalides
      with multiple alkali metal anions. 

PMID- 25583354
TI  - Conducted vasoreactivity: the dynamical point of view.
AB  - Conducted vasodilation is part of the physiological response to increasing
      metabolic demand of the tissue. Similar responses can be elicited by focal
      electrical or chemical stimulation. Some evidence suggests an endothelial pathway
      for nondecremental transmission of hyperpolarizing pulses. However, the
      underlying mechanisms are debated. Here, we focus on dynamical aspects of the
      problem hypothesizing the existence of a bistability-powered mechanism for
      regenerative pulse transmission along the endothelium. Bistability implies that
      the cell can have two different stable resting potentials and can switch between
      those states following an appropriate stimulus. Bistability is possible if the
      current-voltage curve is N shaped instead of monotonically increasing.
      Specifically, the presence of an inwardly rectifying potassium current may
      provide the endothelial cell with such properties. We provide a theoretical
      analysis as well as numerical simulations of both single- and multiunit bistable
      systems mimicking endothelial cells to investigate the self-consistence and
      stability of the proposed mechanism. We find that the individual cell may switch
      readily between two stable potentials. An array of coupled cells, however, as
      found in the vascular wall, requires a certain adaptation of the membrane
      currents after a switch, in order to switch back. Although the formulation is
      generic, we suggest a combination of specific membrane currents that could
      underlie the phenomenon.

PMID- 25583356
TI  - An unrecognized species of the Culicoides obsoletus complex feeding on livestock
      in The Netherlands.
AB  - In studies on Culicoides attacking livestock in the Netherlands, we chanced upon
      a species of the Obsoletus complex that we do not recognize, but whose dark wing
      pattern is distinctive. Nine cytochrome c oxidase (CO1) sequences of our so
      called 'dark obsoletus' support its status as a separate species, the sequences
      differing significantly from those representing Culicoides obsoletus (Meigen) (90
      91% homology) and Culicoides scoticus Downes & Kettle (87-88% homology). In the
      last decade, several research groups in Europe have encountered 'mystery species'
      related to C. obsoletus and in some instances have made their sequences for
      various genetic loci available in GenBank. These include a CO1 series submitted
      from Sweden in 2012 (annotated as 'obsoletus 01, 02, or 03 MA-2012') and of which
      some share a 99% identity with our sequences for 'dark obsoletus'. Without doubt,
      the series from the Netherlands, along with a portion of the Swedish submissions,
      together represent a single species ('dark obsoletus'). Whether this species is
      referable to the Russian Culicoides gornostaevae Mirzaeva recorded recently from
      Norway, Sweden and Poland, and based solely upon the external morphology of the
      male, is not clear. The presence in Western Europe of multiple undescribed
      species related to C. obsoletus means that the taxonomy of this important vector
      complex is not fully resolved; consequently, we know little about these cryptic
      species with regard to seasonality, geographic range and host preference. This is
      undesirable given that Culicoides-borne arboviruses causing disease in livestock
      are moving more regularly out of the tropics and spreading north into temperate
      latitudes. 

PMID- 25583357
TI  - The prevalence of Giardia infection in dogs and cats, a systematic review and
      meta-analysis of prevalence studies from stool samples.
AB  - Giardia has a wide range of host species and is a common cause of diarrhoeal
      disease in humans and animals. Companion animals are able to transmit a range of
      zoonotic diseases to their owners including giardiasis, but the size of this risk
      is not well known. The aim of this study was to analyse giardiasis prevalence
      rates in dogs and cats worldwide using a systematic search approach. Meta
      analysis enabled to describe associations between Giardia prevalence and various
      confounding factors. Pooled prevalence rates were 15.2% (95% CI 13.8-16.7%) for
      dogs and 12% (95% CI 9.2-15.3%) for cats. However, there was very high
      heterogeneity between studies. Meta-regression showed that the diagnostic method
      used had a major impact on reported prevalence with studies using ELISA, IFA and
      PCR reporting prevalence rates between 2.6 and 3.7 times greater than studies
      using microscopy. Conditional negative binomial regression found that symptomatic
      animals had higher prevalence rates ratios (PRR) than asymptomatic animals 1.61
      (95% CI 1.33-1.94) in dogs and 1.94 (95% CI 1.47-2.56) in cats. Giardia was much
      more prevalent in young animals. For cats >6 months, PRR=0.47 (0.42-0.53) and in
      dogs of the same age group PRR=0.36 (0.32-0.41). Additionally, dogs kept as pets
      were less likely to be positive (PRR=0.56 (0.41-0.77)) but any difference in cats
      was not significant. Faecal excretion of Giardia is common in dogs and slightly
      less so in cats. However, the exact rates depend on the diagnostic method used,
      the age and origin of the animal. What risk such endemic colonisation poses to
      human health is still unclear as it will depend not only on prevalence rates but
      also on what assemblages are excreted and how people interact with their pets. 

PMID- 25583359
TI  - Response to: "Enhancing the Characterization of Epistemic Uncertainties in PM2.5
      Risk Analyses".

PMID- 25583358
TI  - CHEK2 mutations and the risk of papillary thyroid cancer.
AB  - Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are
      associated with multi-organ cancer susceptibility including cancers of the breast
      and prostate. A genetic association between thyroid and breast cancer has been
      suggested, however little is known about the determinants of this association. To
      characterize the association of CHEK2 mutations with thyroid cancer, we genotyped
      468 unselected patients with papillary thyroid cancer and 468 (matched) cancer
      free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395
      and I157T). We compared the family histories reported by patients with a CHEK2
      mutation to those of non-carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%)
      unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%)
      age- and sex-matched controls (OR 3.3; p < 0.0001). A truncating mutation (IVS2 +
      1G>A, 1100delC or del5395) was associated with a higher risk of thyroid cancer
      (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p =
      0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2
      times more commonly than non-carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation
      was found in seven of 11 women (63%) with multiple primary cancers of the breast
      and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations
      predispose to thyroid cancer, familial aggregations of breast and thyroid cancer
      and to double primary cancers of the breast and thyroid.

PMID- 25583360
TI  - Interleukin-32gamma attenuates ethanol-induced liver injury by the inhibition of
      cytochrome P450 2E1 expression and inflammatory responses.
AB  - Alcohol abuse and alcoholism lead to alcoholic liver disease (ALD), which is a
      major type of chronic liver disease worldwide. Interleukin-32 (IL-32) is a novel
      cytokine involved in inflammation and cancer development. However, the role of IL
      32 in chronic liver disease has not been reported. In the present paper, we
      tested the effect of IL-32gamma on ethanol-induced liver injury in IL-32gamma
      overexpressing transgenic mice (IL-32gamma mice) after chronic ethanol feeding.
      Male C57BL/6 and IL-32gamma mice (10-12 weeks old) were fed on a Lieber-DeCarli
      diet containing 6.6% ethanol for 6 weeks. IL-32gamma-transfected HepG2 and Huh7
      cells, as well as primary hepatocytes from IL-32gamma mice, were treated with or
      without ethanol. The hepatic steatosis and damage induced by ethanol
      administration were attenuated in IL-32gamma mice. Ethanol-induced cytochrome
      P450 2E1 expression and hydrogen peroxide levels were decreased in the livers of
      IL-32gamma mice, primary hepatocytes from IL-32gamma mice and IL-32gamma
      overexpressing human hepatic cells. The ethanol-induced expression levels of
      cyclo-oxygenase-2 (COX-2) and IL-6 were reduced in the livers of IL-32gamma mice.
      Because nuclear transcription factor kappaB (NF-kappaB) is a key redox
      transcription factor of inflammatory responses, we examined NF-kappaB activity.
      Ethanol-induced NF-kappaB activities were significantly lower in the livers of IL
      32gamma mice than in wild-type (WT) mice. Furthermore, reduced infiltration of
      natural killer cells, cytotoxic T-cells and macrophages in the liver after
      ethanol administration was observed in IL-32gamma mice. These data suggest that
      IL-32gamma prevents ethanol-induced hepatic injury via the inhibition of
      oxidative damage and inflammatory responses. 

PMID- 25583361
TI  - Histidine(7.36(305)) in the conserved peptide receptor activation domain of the
      gonadotropin releasing hormone receptor couples peptide binding and receptor
      activation.
AB  - Transmembrane helix seven residues of G protein-coupled receptors (GPCRs) couple
      agonist binding to a conserved receptor activation mechanism. Amino-terminal
      residues of the GnRH peptide determine agonist activity. We investigated GnRH
      interactions with the His(7.36(305)) residue of the GnRH receptor, using
      functional and computational analysis of modified GnRH receptors and peptides.
      Non-polar His(7.36(305)) substitutions decreased receptor affinity for GnRH four-
      to forty-fold, whereas GnRH signaling potency was more decreased (~150-fold).
      Uncharged polar His(7.36(305)) substitutions decreased GnRH potency, but not
      affinity. [2-Nal(3)]-GnRH retained high affinity at receptors with non-polar
      His(7.36(305)) substitutions, supporting a role for His(7.36(305)) in recognizing
      Trp(3) of GnRH. Compared with GnRH, [2-Nal(3)]-GnRH potency was lower at the wild
      type GnRH receptor, but unchanged or higher at mutant receptors. Results suggest
      that His(7.36(305)) of the GnRH receptor forms two distinct interactions that
      determine binding to Trp(3) and couple agonist binding to the conserved
      transmembrane domain network that activates GPCRs. 

PMID- 25583362
TI  - Role of microRNAs in plant drought tolerance.
AB  - Drought is a normal and recurring climate feature in most parts of the world and
      plays a major role in limiting crop productivity. However, plants have their own
      defence systems to cope with adverse climatic conditions. One of these defence
      mechanisms is the reprogramming of gene expression by microRNAs (miRNAs). miRNAs
      are small noncoding RNAs of approximately 22 nucleotides length, which have
      emerged as important regulators of genes at post-transcriptional levels in a
      range of organisms. Some miRNAs are functionally conserved across plant species
      and are regulated by drought stress. These properties suggest that miRNA-based
      genetic modifications have the potential to enhance drought tolerance in cereal
      crops. This review summarizes the current understanding of the regulatory
      mechanisms of plant miRNAs, involvement of plant miRNAs in drought stress
      responses in barley (Hordeum vulgare L.), wheat (Triticum spp.) and other plant
      species, and the involvement of miRNAs in plant-adaptive mechanisms under drought
      stress. Potential strategies and directions for future miRNA research and the
      utilization of miRNAs in the improvement of cereal crops for drought tolerance
      are also discussed. 

PMID- 25583363
TI  - Investigation of the binding and functional properties of extended length D3
      dopamine receptor-selective antagonists.
AB  - The D3 dopamine receptor represents an important target in drug addiction in that
      reducing receptor activity may attenuate the self-administration of drugs and/or
      disrupt drug or cue-induced relapse. Medicinal chemistry efforts have led to the
      development of D3 preferring antagonists and partial agonists that are >100-fold
      selective vs. the closely related D2 receptor, as best exemplified by extended
      length 4-phenylpiperazine derivatives. Based on the D3 receptor crystal
      structure, these molecules are known to dock to two sites on the receptor where
      the 4-phenylpiperazine moiety binds to the orthosteric site and an extended aryl
      amide moiety docks to a secondary binding pocket. The bivalent nature of the
      receptor binding of these compounds is believed to contribute to their D3
      selectivity. In this study, we examined if such compounds might also be "bitopic"
      such that their aryl amide moieties act as allosteric modulators to further
      enhance the affinities of the full-length molecules for the receptor. First, we
      deconstructed several extended-length D3-selective ligands into fragments, termed
      "synthons", representing either orthosteric or secondary aryl amide
      pharmacophores and investigated their effects on D3 receptor binding and
      function. The orthosteric synthons were found to inhibit radioligand binding and
      to antagonize dopamine activation of the D3 receptor, albeit with lower
      affinities than the full-length compounds. Notably, the aryl amide-based synthons
      had no effect on the affinities or potencies of the orthosteric synthons, nor did
      they have any effect on receptor activation by dopamine. Additionally,
      pharmacological investigation of the full-length D3-selective antagonists
      revealed that these compounds interacted with the D3 receptor in a purely
      competitive manner. Our data further support that the 4-phenylpiperazine D3
      selective antagonists are bivalent and that their enhanced affinity for the D3
      receptor is due to binding at both the orthosteric site as well as a secondary
      binding pocket. Importantly, however, their interactions at the secondary site do
      not allosterically modulate their binding to the orthosteric site. 

PMID- 25583366
TI  - Surface structure of hydrogenated diamond-like carbon: origin of run-in behavior
      prior to superlubricious interfacial shear.
AB  - The oxidized layers at the surface of hydrogenated diamond-like carbon (H-DLC)
      were studied with X-ray photoelectron spectroscopy, near-edge X-ray absorption
      fine structure, and Raman spectroscopy. The structure of these layers was
      correlated with the friction and wear behavior observed on H-DLC. H-DLC is well
      known for its ultralow friction in inert environments, but the steady
      superlubricious state is always preceded by a run-in period with a high friction.
      It was hypothesized that the run-in period is related to the surface oxide layer
      formed naturally upon exposure of the sample to air. To test this hypothesis,
      thermal oxide layers were grown, and their structures were analyzed and compared
      with the native oxide layer on a pristine sample. It was found that the Raman
      spectra of the surface oxide layers of H-DLC have higher D/G band ratio than the
      bulk, indicating a larger amount of aromatic clusters compared to the bulk film.
      Thick oxide layers grown at 300  degrees C showed a run-in friction behavior that
      resembled the friction of graphite. The run-in periods were found to become
      longer when the thickness of the oxide layers increased, indicating that the run
      in behavior of H-DLC is attributed to the removal of the surface oxide layers. 

PMID- 25583365
TI  - CIRI: an efficient and unbiased algorithm for de novo circular RNA
      identification.
AB  - Recent studies reveal that circular RNAs (circRNAs) are a novel class of
      abundant, stable and ubiquitous noncoding RNA molecules in animals. Comprehensive
      detection of circRNAs from high-throughput transcriptome data is an initial and
      crucial step to study their biogenesis and function. Here, we present a novel
      chiastic clipping signal-based algorithm, CIRI, to unbiasedly and accurately
      detect circRNAs from transcriptome data by employing multiple filtration
      strategies. By applying CIRI to ENCODE RNA-seq data, we for the first time
      identify and experimentally validate the prevalence of intronic/intergenic
      circRNAs as well as fragments specific to them in the human transcriptome. 

PMID- 25583364
TI  - Cardiac effects of sertindole and quetiapine: analysis of ECGs from a randomized
      double-blind study in patients with schizophrenia.
AB  - The QT interval is the most widely used surrogate marker for predicting TdP;
      however, several alternative surrogate markers, such as Tpeak-Tend (TpTe) and a
      quantitative T-wave morphology combination score (MCS) have emerged. This study
      investigated the cardiac effects of sertindole and quetiapine using the QTc
      interval and newer surrogate markers. Data were derived from a 12 week randomized
      double-blind study comparing flexible dosage of sertindole 12-20mg and quetiapine
      400-600mg in patients with schizophrenia. ECGs were recorded digitally at
      baseline and after 3, 6 and 12 weeks. Between group effects were compared by
      using a mixed effect model, whereas assessment within group was compared by using
      a paired t-test. Treatment with sertindole was associated with QTcF and QTcB
      interval prolongation and an increase in MCS, T-wave asymmetry, T-wave flatness
      and TpTe. The mean increase in QTcF from baseline to last observation was 12.1ms
      for sertindole (p<0.001) and -0.5ms for quetiapine (p=0.8). Quetiapine caused no
      increase in MCS, T-wave asymmetry, T-wave flatness or TpTe compared to baseline.
      In the categorical analysis, there were 11 patients (9.6%) receiving quetiapine
      who experienced more than 20ms QTcF prolongation compared with 36 patients
      (33.3%) in the sertindole group. Sertindole (12-20mg) was associated with
      moderate QTc prolongation and worsening of T-wave morphology in a study
      population of patients with schizophrenia. Although, quetiapine (400-600mg) did
      not show worsening of repolarization measures some individual patients did
      experience significant worsening of repolarization. Clinical Trials NCT00654706.

PMID- 25583367
TI  - Expeditious entry to the chamigrane endoperoxide family of natural products.
AB  - Several members of the recently reported peroxy chamigrane family of natural
      products were synthesized via a distereoselective route with a novel facial
      selective epoxidation of a spiroundecadiene, a facile epoxide rearrangement, and
      a Co(II)-mediated silylperoxidation as the key steps. Adaptation of the
      diastereoselective route to an enantioselective one is also illustrated. 

PMID- 25583368
TI  - Engineering two-dimensional superconductivity and Rashba spin-orbit coupling in
      LaAlO3/SrTiO3 quantum wells by selective orbital occupancy.
AB  - The discovery of two-dimensional electron gases (2DEGs) at oxide interfaces
      involving electrons in narrow d-bands-has broken new ground, enabling the access
      to correlated states that are unreachable in conventional semiconductors based on
      s- and p- electrons. There is a growing consensus that emerging properties at
      these novel quantum wells-such as 2D superconductivity and magnetism-are
      intimately connected to specific orbital symmetries in the 2DEG sub-band
      structure. Here we show that crystal orientation allows selective orbital
      occupancy, disclosing unprecedented ways to tailor the 2DEG properties. By
      carrying out electrostatic gating experiments in LaAlO3/SrTiO3 wells of different
      crystal orientations, we show that the spatial extension and anisotropy of the 2D
      superconductivity and the Rashba spin-orbit field can be largely modulated by
      controlling the 2DEG sub-band filling. Such an orientational tuning expands the
      possibilities for electronic engineering of 2DEGs at LaAlO3/SrTiO3 interfaces. 

PMID- 25583369
TI  - Mycophenolate mofetil in erosive genital lichen planus: a case and review of the
      literature.
AB  - Erosive genital lichen planus is a disabling, inflammatory mucocutaneous
      condition that can cause significant patient morbidity and loss of function.
      Treatment initially involves topical corticosteroids but some patients can have
      severe treatment-resistant courses requiring systemic immunosuppression. With
      potentially unfavorable adverse effect profiles and subsequent intolerance of
      these agents by patients, erosive lichen planus can ultimately be a challenging
      condition to treat effectively. We present a case of a 66-year-old woman with
      treatment-resistant erosive genital lichen planus who was successfully managed
      with mycophenolate mofetil. Although there is only weak evidence for this agent
      in this condition, its role in dermatology is growing due to its efficacy and
      advantageous adverse effect profile and should therefore be considered in
      patients with treatment-resistant erosive genital lichen planus. 

PMID- 25583370
TI  - Flagellar filament bio-templated inorganic oxide materials - towards an efficient
      lithium battery anode.
AB  - Designing a new generation of energy-intensive and sustainable electrode
      materials for batteries to power a variety of applications is an imperative task.
      The use of biomaterials as a nanosized structural template for these materials
      has the potential to produce hitherto unachievable structures. In this report, we
      have used genetically modified flagellar filaments of the extremely halophilic
      archaea species Halobacterium salinarum to synthesize nanostructured iron oxide
      composites for use as a lithium-ion battery anode. The electrode demonstrated a
      superior electrochemical performance compared to existing literature results,
      with good capacity retention of 1032 mAh g(-1) after 50 cycles and with high rate
      capability, delivering 770 mAh g(-1) at 5 A g(-1) (~5 C) discharge rate. This
      unique flagellar filament based template has the potential to provide access to
      other highly structured advanced energy materials in the future. 

PMID- 25583372
TI  - Obesity and breast cancer: study of a group of female patients in granada
      (Spain).

PMID- 25583371
TI  - Symptom severity as a risk factor for self-injurious behaviours in adolescents
      with autism spectrum disorders.
AB  - BACKGROUND: Self-injurious behaviours (SIB) are highly prevalent in individuals
      with autism spectrum disorders (ASD) and have deleterious effects on the
      individual and their environment. The aim of this study was to examine SIB
      prevalence and associated features in a population of 152 adolescents with ASD
      and to determine risk factors for SIB. METHODS: The present study uses a subset
      of data of a longitudinal follow-up of 152 children with ASD. The presence of a
      low or high level of self-injury was assessed at adolescence through the Aberrant
      Behaviour Checklist completed by parents. Clinical and social variables regarding
      severity of autism symptoms, psychological development, adaptive behaviours,
      parental quality of life and total intervention time were collected during
      childhood (mean age = 5 years, SD = 1.6) and at adolescence (mean age = 15 years,
      SD = 1.3). RESULTS: About 35.8% of adolescents with ASD in our sample displayed
      self-injury, which was frequently associated with other challenging behaviours
      and was related to severity of autism symptoms, adaptive skills, intellectual
      functioning and language level (P < 0.001). The main risk factor for SIB at
      adolescence was severity of autism symptoms (P = 0.04). Cognitive development
      during childhood was found to be a protective factor (P = 0.03) whereas at
      adolescence, the main protective factor was communicative abilities (P = 0.04).
      CONCLUSIONS: These data showed that SIB remained highly prevalent at adolescence
      and yielded risk and protective factors for developing SIB at this period of
      life. Limitations and perspectives for future research are discussed.

PMID- 25583373
TI  - "Whatever I have, I have made by coming into this profession": the intersection
      of resources, agency, and achievements in pathways to sex work in Kolkata, India.
AB  - This article investigated the complex interplay of choice, socioeconomic
      structural factors, and empowerment influencing engagement in sex work. The
      analysis was focused on pathways into and reasons for staying in sex work from in
      depth qualitative interviews with participants (n = 37) recruited from the Durbar
      community-led structural intervention in Kolkata, India. Kabeer's theory of
      empowerment focused on resources, agency, and achievements was utilized to
      interpret the results. Results identified that contexts of disempowerment
      constraining resources and agency set the stage for initiating sex work,
      typically due to familial poverty, loss of a father or husband as a breadwinner,
      and lack of economic opportunities for women in India. Labor force participation
      in informal sectors was common, specifically in domestic, construction, and
      manufacturing work, but was typically insufficient to provide for families and
      also often contingent on sexual favors. The availability of an urban market for
      sex work served as a catalyst or resource, in conjunction with Durbar's
      programmatic resources, for women to find and exercise agency and achieve
      financial and personal autonomy not possible in other work or as dependents on
      male partners. Resources lost in becoming a sex worker due to stigma,
      discrimination, and rejection by family and communities were compensated for by
      achievements in gaining financial and social resources, personal autonomy and
      independence, and the ability to support children and extended family. Durbar's
      programs and activities (e.g., savings and lending cooperative, community
      mobilization, advocacy) function as empowering resources that are tightly linked
      to sex workers' agency, achievements, and sex work pathways.

PMID- 25583375
TI  - Individual, partner, and partnership level correlates of anal sex among youth in
      Baltimore City.
AB  - Anal sex is an efficient mode of STI transmission and studies indicate that anal
      sex is common among heterosexuals, including adolescents. We examined the
      association between individual, partner, and sexual partnership-level
      characteristics with anal sex among a household survey of 263 individuals aged 15
      24 years in Baltimore City, Maryland. We used weighted multiple logistic
      regression to examine correlates of anal sex in a heterosexual partnership by
      gender. Twenty-nine percent of males and 15% of females reported anal sex in a
      partnership in the past 6 months. For males, anal sex was associated with having
      two or more partners in the past 3 months (AOR = 13.93, 95% CI 3.87-50.12),
      having been tested for HIV (AOR = 0.30, 95% CI 0.12-0.72), and oral sex with a
      partner (AOR = 8.79, 95% CI 1.94-39.78). For females, anal sex was associated
      with reporting having a main partner (AOR = 6.74, 95% CI 1.74-23.65), partner
      meeting place (AOR = 3.03, 95% CI 1.04-8.82), partner history of STI (AOR = 0.20,
      95% CI 0.05-0.85), and oral sex with a partner (AOR = 8.47, 95% CI 1.08-66.25).
      Anal sex was associated with inconsistent condom use for both males (OR = 5.77,
      95% CI 1.68-19.79) and females (OR = 5.16, 95% CI 1.46-18.30). We conclude that
      anal sex is a prevalent risk behavior among heterosexual youth and is associated
      with a range of factors at the individual and partnership levels. These findings
      provide support for comprehensive sex education that includes information about
      anal sex; findings from this study can inform public health campaigns targeting
      youth at risk for STIs.

PMID- 25583374
TI  - "Bend a fish when the fish is not yet dry": adolescent boys' perceptions of
      sexual risk in Tanzania.
AB  - Despite decades of effort, the spread of HIV/AIDS continues among many African
      young people. A key contributor is unsafe sexual behavior that is desired,
      persuaded, or coerced. We explored the masculinity norms shaping pubescent boys'
      perceptions of and engagement in (unsafe) sexual behaviors in Tanzania. Through a
      comparative case study in rural and urban Tanzania, qualitative and participatory
      methods were used with 160 adolescent boys in and out of school to better
      understand the social and contextual factors promoting unsafe sexual behaviors.
      Adolescent boys in both the rural and urban sites reported struggling with
      intense sexual desires, strong peer pressures to have sex, and social norms
      dissuading condom use. A growing "normalization" of AIDS suggests messages
      promoting the dangers of HIV infection may be less effective. Findings reinforce
      the need for interventions with very young adolescents. Research is needed to
      identify more effective approaches for promoting safer sexual practices among
      boys in sub-Saharan Africa. Harm reduction approaches and gender transformative
      approaches might prove more effective than current HIV prevention efforts focused
      on youth. 

PMID- 25583376
TI  - The sensitivity of QBA assessments of sheep behavioural expression to variations
      in visual or verbal information provided to observers.
AB  - Qualitative behavioural assessment (QBA) is based on observers' ability to
      capture the dynamic complexity of an animal's demeanour as it interacts with the
      environment, in terms such as tense, anxious or relaxed. Sensitivity to context
      is part of QBA's integrative capacity and discriminatory power; however, when not
      properly managed it can also be a source of undesirable variability and bias.
      This study investigated the sensitivity of QBA to variations in the visual or
      verbal information provided to observers, using free-choice profiling (FCP)
      methodology. FCP allows observers to generate their own descriptive terms for
      animal demeanour, against which each animal's expressions are quantified on a
      visual analogue scale. The resulting scores were analysed with Generalised
      Procrustes Analysis (GPA), generating two or more multi-variate dimensions of
      animal expression. Study 1 examined how 63 observers rated the same video clips
      of individual sheep during land transport, when these clips were interspersed
      with two different sets of video footage. Scores attributed to the sheep in the
      two viewing sessions correlated significantly (GPA dimension 1: r s =0.95,
      P<0.001, GPA dimension 2: r s =0.66, P=0.037) indicating that comparative
      rankings of animals on expressive dimensions were highly similar, however, their
      mean numerical scores on these dimensions had shifted (RM-ANOVA: Dim1: P<0.001,
      Dim2: P<0.001). Study 2 investigated the effect of being given different amounts
      of background information on two separate groups of observers assessing footage
      of 22 individual sheep in a behavioural demand facility. One group was given no
      contextual information regarding this facility, whereas the second group was told
      that animals were moving towards and away from a feeder (in view) to access feed.
      Scores attributed to individual sheep by the two observer groups correlated
      significantly (Dim1: r s =0.92, P<0.001, Dim2: r s =0.52, P=0.013). A number of
      descriptive terms were generated by both observer groups and used in similar
      ways, other terms were unique to each group. The group given additional
      information about the experimental facility scored the sheep's behaviour as more
      'directed' and 'focused' than observers who had not been told. Thus, in neither
      of the two studies did experimentally imposed variations in context alter the
      characterisations of animals relative to each other, but in Study 1 this did
      affect the mean numerical values underlying these characterisations, indicating a
      need for careful attention to the use of visual analogue scales. 

PMID- 25583377
TI  - Survival in rheumatoid arthritis-associated pulmonary arterial hypertension
      compared with idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND AND OBJECTIVE: In this study, we evaluated survival in rheumatoid
      arthritis-associated pulmonary arterial hypertension (RA-PAH) compared with
      idiopathic pulmonary arterial hypertension (IPAH) patients, and evaluate
      differences in disease severity and treatment. METHODS: We conducted a
      retrospective cohort study of RA-PAH and IPAH at the University Health Network
      Pulmonary Hypertension Programme, Toronto, Canada. The primary outcome was time
      to all-cause mortality. We evaluated survival using Kaplan-Meier curves. Using a
      propensity score-matched cohort, we used Cox proportional hazards models to
      estimate survival. RESULTS: Screening 1385 patients identified 18 RA-PAH and 155
      IPAH patients. RA-PAH patients had an older median age of onset (64.0 vs 53.7
      years) and lower baseline mean pulmonary arterial pressure (mPAP) (41 vs 50 mm
      Hg, P = 0.02). RA-PAH patients tended to have a higher proportion of females (83%
      vs 70%, relative risk 0.55, 95% confidence interval (CI): 0.19-1.57), lower
      proportion with baseline World Health Organization functional class III/IV (39%
      vs 52%), lower median baseline brain natriuretic peptide (58.4 vs 95.0 pg/mL) and
      longer baseline 6-min walk distance (440 vs 397 m). There were 35 deaths, 2/18
      (11%) RA-PAH patients and 33/155 (21%) IPAH patients. The unadjusted 1-year
      survival was 93% for RA-PAH and 94% for IPAH. In the matched cohort, there were
      seven deaths: 2/18 (11%) RA-PAH and 5/18 (28%) IPAH patients, hazard ratio 1.53
      (95% CI: 0.15-2.84). Separation of survival curves did not achieve statistical
      significance, log-rank 0.56. CONCLUSIONS: Compared with IPAH patients, RA-PAH
      patients have an older age of onset and lower baseline mPAP. RA-PAH patients have
      comparable survival to IPAH patients.

PMID- 25583378
TI  - Salivary cortisol levels are elevated in the afternoon and at bedtime in children
      with prenatal alcohol exposure.
AB  - Prenatal alcohol exposure can cause dysregulation of the hypothalamic-pituitary
      adrenal (HPA) axis, which may underlie some of the behavioral and adaptive
      problems seen in individuals with Fetal Alcohol Spectrum Disorders (FASD).
      Infants prenatally exposed to alcohol show altered basal and post-stress cortisol
      levels, but it is unknown if this persists beyond 2 years of age. It is also
      unknown if cortisol levels can be normalized through intervention programs. In
      this study, we investigated the effects of a physical activity program for
      children with FASD to determine: 1) if HPA dysregulation persists in school-age
      children with FASD, and 2) the effect of our program on cortisol levels. Twenty
      six children (ages 6-14 years) with FASD participated in an 8 week motor skill
      development program. Salivary cortisol levels were measured in 24 children and
      compared at 4 time points: before, immediately after, 3 months, and 1 year after
      program completion. Cortisol levels were also compared to 32 control children to
      evaluate the long-term effects of prenatal alcohol exposure on HPA regulation.
      For each time point, saliva was collected on each of 2 days at 3 times in the
      diurnal cycle: awakening, after school, and just before bedtime. Cortisol levels
      were significantly higher in the afternoon and at bedtime in children with FASD
      with confirmed prenatal exposure to high levels of alcohol (alcohol exposure rank
      4), compared with Control children or children with FASD with exposure to low or
      unknown levels of alcohol (alcohol exposure rank 3). The program did not
      significantly affect cortisol levels in children with FASD as a group. These
      results provide support for long-term effects of prenatal alcohol exposure on the
      HPA system in humans, which could increase vulnerability to mental health issues
      and diseases later in life. 

PMID- 25583379
TI  - Predatory publishers: authors beware.

PMID- 25583380
TI  - Who is helping whom? Manuscript support and transfer of value.

PMID- 25583381
TI  - A new algorithm for spatiotemporal analysis of brain functional connectivity.
AB  - Specific networks of interacting neuronal assemblies distributed within and
      across distinct brain regions underlie brain functions. In most cognitive tasks,
      these interactions are dynamic and take place at the millisecond time scale.
      Among neuroimaging techniques, magneto/electroencephalography - M/EEG - allows
      for detection of very short-duration events and offers the single opportunity to
      follow, in time, the dynamic properties of cognitive processes (sub-millisecond
      temporal resolution). In this paper, we propose a new algorithm to track the
      functional brain connectivity dynamics. During a picture naming task, this
      algorithm aims at segmenting high-resolution EEG signals (hr-EEG) into functional
      connectivity microstates. The proposed algorithm is based on the K-means
      clustering of the connectivity graphs obtained from the phase locking value (PLV)
      method applied on hr-EEG. Results show that the analyzed evoked responses can be
      divided into six clusters representing distinct networks sequentially involved
      during the cognitive task, from the picture presentation and recognition to the
      motor response. 

PMID- 25583382
TI  - Time course of neuronal death following endothelin-1 induced focal ischemia in
      rats.
AB  - BACKGROUND: Endothelin-1 (ET-1) induced focal ischemia is increasingly being used
      as a preclinical model of stroke. Here, we described for the first time, the time
      course of neuronal death and infarct evolution during the first 7 days following
      ischemia. NEW METHOD: We used hematoxylin and eosin (H&E) staining to evaluate
      infarct progression and Fluoro-Jade C (FJC) to quantify neuronal degeneration at
      24, 48, 72h and 7 days after ET-1 injection to the forelimb motor cortex in
      Sprague-Dawley rats. RESULTS: We found that infarct volume and neuronal
      degeneration are maximal at 24h post-stroke. Neuronal degeneration is also
      significantly reduced within 7 days of stroke induction. COMPARISON WITH EXISTING
      METHOD: This study is the first to provide a direct evaluation of both infarct
      volume evolution and neuronal death time course following ET-1 induced focal
      ischemia in the forelimb motor cortex. CONCLUSION: This study describes the short
      term time course of neuronal death and brain injury in the ET-1 stroke model,
      which provides a significant reference when determining the appropriate time to
      commence neuroprotective or recovery promoting strategies.

PMID- 25583384
TI  - Vaccine-criticism on the internet: new insights based on French-speaking
      websites.
AB  - The internet is playing an increasingly important part in fueling vaccine related
      controversies and in generating vaccine hesitant behaviors. English language
      Antivaccination websites have been thoroughly analyzed, however, little is known
      of the arguments presented in other languages on the internet. This study
      presents three types of results: (1) Authors apply a time tested content analysis
      methodology to describe the information diffused by French language vaccine
      critical websites in comparison with English speaking websites. The contents of
      French language vaccine critical websites are very similar to those of English
      language websites except for the relative absence of moral and religious
      arguments. (2) Authors evaluate the likelihood that internet users will find
      those websites through vaccine-related queries on a variety of French-language
      versions of google. Queries on controversial vaccines generated many more vaccine
      critical websites than queries on vaccination in general. (3) Authors propose a
      typology of vaccine critical websites. Authors distinguish between (a) websites
      that criticize all vaccines ("antivaccine" websites) and websites that criticize
      only some vaccines ("vaccine-selective" websites), and between (b) websites that
      focus on vaccines ("vaccine-focused" websites) and those for which vaccines were
      only a secondary topic of interest ("generalist" websites). The differences in
      stances by groups and websites affect the likelihood that they will be believed
      and by whom. This study therefore helps understand the different information
      landscapes that may contribute to the variety of forms of vaccine hesitancy.
      Public authorities should have better awareness and understanding of these
      stances to bring appropriate answers to the different controversies about
      vaccination. 

PMID- 25583383
TI  - Active inference and oculomotor pursuit: the dynamic causal modelling of eye
      movements.
AB  - BACKGROUND: This paper introduces a new paradigm that allows one to quantify the
      Bayesian beliefs evidenced by subjects during oculomotor pursuit. Subjects' eye
      tracking responses to a partially occluded sinusoidal target were recorded non
      invasively and averaged. These response averages were then analysed using dynamic
      causal modelling (DCM). In DCM, observed responses are modelled using
      biologically plausible generative or forward models - usually biophysical models
      of neuronal activity. NEW METHOD: Our key innovation is to use a generative model
      based on a normative (Bayes-optimal) model of active inference to model
      oculomotor pursuit in terms of subjects' beliefs about how visual targets move
      and how their oculomotor system responds. Our aim here is to establish the face
      validity of the approach, by manipulating the content and precision of sensory
      information - and examining the ensuing changes in the subjects' implicit
      beliefs. These beliefs are inferred from their eye movements using the normative
      model. RESULTS: We show that on average, subjects respond to an increase in the
      'noise' of target motion by increasing sensory precision in their models of the
      target trajectory. In other words, they attend more to the sensory attributes of
      a noisier stimulus. Conversely, subjects only change kinetic parameters in their
      model but not precision, in response to increased target speed. CONCLUSIONS:
      Using this technique one can estimate the precisions of subjects' hierarchical
      Bayesian beliefs about target motion. We hope to apply this paradigm to subjects
      with schizophrenia, whose pursuit abnormalities may result from the abnormal
      encoding of precision.

PMID- 25583385
TI  - Early cellular immune response to a new candidate mycobacterial vaccine antigen
      in childhood tuberculosis.
AB  - The search for novel vaccines against tuberculosis (TB) would benefit from in
      depths knowledge of the human immune responses to Mycobacterium tuberculosis
      (Mtb) infection. Here, we characterised in a low TB incidence country, the immune
      responses to a new candidate vaccine antigen against TB, the heparin-binding
      haemagglutinin (HBHA), in young children in contact with an active TB case (aTB).
      Children with no history of BCG vaccination were compared to those vaccinated at
      birth to compare the initial immune responses to HBHA with secondary immune
      responses. Fifty-eight children with aTB and 76 with latent TB infection (LTBI)
      were included and they were compared to 90 non-infected children. Whereas Mtb
      infected children globally secreted more interferon-gamma (IFN-gamma) in response
      to HBHA compared to the non-infected children, these IFN-gamma concentrations
      were higher in previously BCG-vaccinated compared to non-vaccinated children. The
      IFN-gamma concentrations were similar in LTBI and aTB children, but appeared to
      differ qualitatively. Whereas the IFN-gamma secretion induced by native
      methylated and recombinant non-methylated HBHA were well correlated for aTB, this
      was not the case for LTBI children. Thus, Mtb-infected young children develop IFN
      gamma responses to HBHA that are enhanced by prior BCG vaccination, indicating
      BCG-induced priming, thereby supporting a prime-boost strategy for HBHA-based
      vaccines. The qualitative differences between aTB and LTBI in their HBHA-induced
      IFN-gamma responses may perhaps be exploited for diagnostic purposes. 

PMID- 25583386
TI  - Adults with congenital limb deficiency in Norway: demographic and clinical
      features, pain and the use of health care and welfare services. A cross-sectional
      study.
AB  - PURPOSE: To describe an adult population with congenital limb deficiency (CLD)
      recruited through the National Resource Centre for Rare Disorders (TRS) in
      Norway: (1) demographic factors, (2) clinical features, (3) pain and (4) use of
      health care and welfare services. METHODS: Cross-sectional study. In 2012, a
      postal questionnaire was sent to 186 eligible persons with CLD, age 20 years and
      older. RESULTS: Ninety-seven respondents, median-age 39 years (range: 20-82); 71%
      were women. The population was divided into two subgroups: (1) unilateral upper
      limb deficiency (UULD) n = 77, (2) multiple and/or lower-limb deficiency
      (MLD/LLD). About 40% worked full-time, 18% received disability pensions and 64%
      reported chronic pain, mostly bilateral pain. Grip-improving devices were used
      more often than prostheses; 23% were previous prosthesis users. Use of health
      care and welfare services are described. No significant differences were found
      between the subgroups regarding pain or employment status. CONCLUSIONS: Persons
      with CLD reported increased prevalence of chronic pain, mostly bilateral, and
      increased prevalence of early retirement. A greater focus on the benefits of the
      use of assistive devices, the consequences of overuse and vocational guidance may
      moderate pain and prevent early retirement. Further studies of more
      representative samples should be conducted to confirm our findings. IMPLICATIONS
      FOR REHABILITATION: Most adults with congenital limb deficiency (CLD) live
      ordinary lives and experience normal life events. However, several report chronic
      pain and retire before normal retirement age. In spite of free and accessible
      prosthetic services, a large fraction chooses not to use prosthesis, more use
      grip-improving devices for specific activities. These preferences should be
      acknowledged by rehabilitation specialists. Focus on individually adapted
      environments, more information about the consequences of overuse, and vocational
      guidance may moderate pain and prevent early retirement.

PMID- 25583387
TI  - Human cytomegalovirus miR-US33-5p inhibits viral DNA synthesis and viral
      replication by down-regulating expression of the host Syntaxin3.
AB  - During infection with human cytomegalovirus (HCMV), overexpression of hcmv-miR
      US33 can inhibit the lytic viral replication and down-regulate US29 mRNA.
      However, it remains unknown whether inhibition of viral replication by miR-US33
      is mediated by down-regulation of expression of US29 or another host gene. Here,
      we identified the host gene Syntaxin3 (STX3) to be a direct target of hcmv-miR
      US33-5p using Hybrid-PCR and luciferase-reporter assays. It was further
      demonstrated that the levels of STX3 protein were down-regulated in hcmv-miR-US33
      5p-overexpressing cells. Experiments with STX3-specific siRNA, or with an
      inhibitor of hcmv-miR-US33-5p confirmed that hcmv-miR-US33-5p-mediated inhibition
      of HCMV DNA synthesis and of viral replication are specifically mediated by down
      regulation of STX3 expression. 

PMID- 25583388
TI  - Insights into the structure of the diiron site of RIC from Escherichia coli.
AB  - Repair of Iron Centres (RICs) are a widely-spread family of diiron proteins
      involved in the protection of iron-sulphur-containing enzymes from nitrosative
      and oxidative stress. Here, homology-based modelling was used to predict putative
      ligands of the RIC diiron centre in E. coli. Site-directed mutagenesis studies
      showed that several conserved residues modulate the spectroscopic properties of
      the diiron centre, and mutations in H129, E133 and E208 abrogated RIC ability to
      protect aconitase. Taken together, these data led to a structural model of a
      diiron centre inserted in a four-helix bundle fold and coordinated by H84, H129,
      H160, H204, E133 and E208. Moreover, two MU-carboxylate bridges involving E133
      and E208 were found to be required for assembly of a stable diiron centre. 

PMID- 25583389
TI  - Immaturity of human stem-cell-derived cardiomyocytes in culture: fatal flaw or
      soluble problem?
AB  - Cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are increasingly used
      to model cardiac disease, test drug efficacy and for safety pharmacology.
      Nevertheless, a major hurdle to more extensive use is their immaturity and
      similarity to fetal rather than adult cardiomyocytes. Here, we provide an
      overview of the strategies currently being used to increase maturation in
      culture, which include prolongation of time in culture, exposure to electrical
      stimulation, application of mechanical strain, growth in three-dimensional tissue
      configuration, addition of non-cardiomyocytes, use of hormones and small
      molecules, and alteration of the extracellular environment. By comparing the
      outcomes of these studies, we identify the approaches most likely to improve
      functional maturation of hPSC-CMs in terms of their electrophysiology and
      excitation-contraction coupling. 

PMID- 25583390
TI  - Rare case of dysphagia in an elderly patient.

PMID- 25583391
TI  - Intestinal perforation as the initial presentation of polyarteritis nodosa in an
      older adult.

PMID- 25583392
TI  - Hemiparkinsonism-hemiatrophy syndrome with Alzheimer's disease.

PMID- 25583393
TI  - Tracheal stenosis caused by severe tortuosity of the brachiocephalic artery.

PMID- 25583394
TI  - Charles Bonnet syndrome in an 88-year-old woman with retinitis pigmentosa.

PMID- 25583395
TI  - Animal naming in the Spanish version of the Montreal Cognitive Assessment in
      rural Latin American communities: a cautionary note.

PMID- 25583396
TI  - Basal ganglia calcifications on brain computed tomography are also common in
      other elderly populations.

PMID- 25583397
TI  - Delirium reversibility and instrumental activities of daily living.

PMID- 25583398
TI  - Is complex obstacle negotiation exercise more effective than other exercise
      interventions in fall prevention?

PMID- 25583400
TI  - Should emergency medicine registrars focus on seeing patients and leave the
      teaching of medical students to others? Yes.

PMID- 25583399
TI  - Influence of ultrasound determination of fetal head position on mode of delivery:
      a pragmatic randomized trial.
AB  - OBJECTIVE: To evaluate the influence of ultrasound determination of fetal head
      position on mode of delivery. METHODS: This was a pragmatic open-label randomized
      controlled trial that included women with a singleton pregnancy in the vertex
      presentation at >= 37 weeks' gestation, cervical dilation >= 8 cm and who
      received epidural anesthesia. Women were assigned randomly to undergo either
      digital vaginal examination (VE group) or both digital vaginal and ultrasound
      examinations (VE+US group) to determine fetal head position. When the ultrasound
      and digital vaginal findings were inconsistent in the VE+US group, the ultrasound
      result was used for clinical management. The primary outcome assessed was
      operative delivery (Cesarean or instrumental vaginal delivery), and maternal and
      fetal morbidity were also assessed. RESULTS: The VE and VE+US groups included 959
      and 944 women, respectively. The overall rate of operative delivery was
      significantly higher in the VE+US group than in the VE group: 33.7% vs 27.1%,
      respectively (relative risk (RR), 1.24 (95% CI, 1.08-1.43)), as was the rate of
      Cesarean delivery: 7.8% vs 4.9%, respectively (RR, 1.60 (95% CI, 1.12-2.28)). The
      rate of instrumental vaginal delivery was also higher, albeit not significantly:
      25.8% in the VE+US group vs 22.2% in the VE group (RR, 1.16 (95% CI, 0.99-1.37)).
      Neonatal outcomes did not differ between the two groups. When analysis was
      restricted to instrumental vaginal deliveries only, maternal and neonatal
      morbidity outcomes were similar in both groups. CONCLUSION: Correction of fetal
      occiput position, determined initially by digital vaginal examination, using
      systematic ultrasound examination did not improve management of labor and
      increased the rate of operative delivery without decreasing maternal and neonatal
      morbidity.

PMID- 25583401
TI  - Direct anterior Hueter approach is a safe and effective approach to perform a
      bipolar hemiarthroplasty for femoral neck fracture: outcome in 82 patients.
AB  - BACKGROUND AND PURPOSE: The direct anterior (DA) approach in total hip
      arthroplasty has recently been associated with faster functional recovery than
      the posterolateral (PL) approach. We hypothesized that the same should hold for
      the DA approach in bipolar hemiarthroplasty for femoral neck fractures. PATIENTS
      AND METHODS: 82 patients with a displaced femoral neck fracture and candidates
      for bipolar hemiarthroplasty were enrolled after IRB approval in this prospective
      non-randomized comparative study (DA: n = 38; PL: n = 44). The postoperative
      protocols were similar in both groups. Evaluation included surgical
      complications, component placement, and early functional outcomes, assessed 6
      weeks postoperatively using a timed up-and-go (TUG) test. The incidence of
      dislocation was assessed by telephone interview at least 1 year after the
      surgery. RESULTS: The DA-group patients had better results in the TUG test than
      the PL-group patients 6 weeks after surgery: half were under 19 seconds as
      opposed to only one third for PL (p = 0.06). We did not record any intraoperative
      femoral fracture or any lateral femoral cutaneous neuropraxia in the DA group. We
      observed a significant difference (p = 0.04) in lateral offset between the PL
      group (4.2 (SD 6.4) mm) and the DA group (-1.6 (SD 8.5) mm). Stem alignment was
      similar between groups. The dislocation rate for DA patients was lower than for
      PL patients (1 of 38 cases vs. 9 of 44 cases; p = 0.02). INTERPRETATION: Our
      findings indicate that relative to the posterolateral approach, the direct
      anterior approach for bipolar hemiarthroplasty may improve gait in the early
      postoperative period and decrease the dislocation rate.

PMID- 25583403
TI  - Personal Reflections on a Suicide.

PMID- 25583402
TI  - Factors affecting recruitment into psychiatry: a canadian experience.
AB  - OBJECTIVE: There is a projected shortage of psychiatrists in Canada in
      forthcoming years. This study assessed factors in medical school education that
      are associated with students selecting psychiatry first and matching as a
      discipline. METHOD: The Canadian Organization of Undergraduate Psychiatry
      Educators (COUPE) conducted telephone interviews and sent e-mail questionnaires
      to the 17 medical schools across Canada; all schools provided data for 2012.
      Relevant data were obtained from the Canadian Resident Matching Service.
      Statistics were performed using v12 STATA program, and significance was set at a
      p value of <0.05. RESULTS: Medical student enrollment ranged from 54 to 266
      students (mean = 158 +/- 16). Of these students, 4.9 +/- 0.6 % ranked psychiatry
      as their first choice for residency. Final match results yielded similar numbers
      at 5.0 +/- 0.6 %. Ten out of 17 programs filled all psychiatry residency
      positions, whereas the remaining 7 programs had vacancy rates from 5 to 100 %
      (mean = 43.4 +/- 15.1 %). Medical students were exposed to an average of 2.8 +/-
      0.5 pre-clerkship psychiatry weeks and 6.2 +/- 0.3 clerkship weeks. Linear
      regression analysis demonstrated that the percentage of graduating medical
      students entering a psychiatry residency program could be predicted from the
      number of weeks of pre-clerkship exposure (p = 0.01; R(2) = 0.36) but not from
      the number of clerkship weeks (p = 0.74). CONCLUSIONS: This study indicates that
      the duration of pre-clerkship exposure to psychiatry predicts the number of
      students selecting psychiatry as their first choice as a discipline. Thus,
      increasing the duration of pre-clerkship exposure may increase the enrollment of
      medical students into psychiatry.

PMID- 25583404
TI  - Integrating a College Mental Health Track into a Public Psychiatry Fellowship.

PMID- 25583405
TI  - Nurses' communication with families in the intensive care unit - a literature
      review.
AB  - AIMS AND OBJECTIVES: This review examined the literature across 12 years that
      explored nurses' perceptions of their role when communicating with families in
      adult intensive care units (ICUs). The objectives were: (1) to describe how ICU
      nurses facilitated communication with families; (2) the perceived barriers to
      that communication; (3) strategies to improve their skills. BACKGROUND: Evidence
      demonstrates that effective communication by health care providers can improve
      families' understanding of their situation and decrease their psychological
      burden. The continuous presence of ICU nurses, combined with the use of effective
      empathic communication skills, can impact on families' ICU experience in a
      positive way. Nevertheless, research continues to demonstrate that communication
      with families in ICU is inadequate and of poor quality. SEARCH STRATEGIES AND
      DESIGN: Eight databases were systematically searched to identify peer reviewed
      studies published in English between 2002 and 2014. The results are presented via
      a thematic literature review. FINDINGS: Four major themes emerged from a
      synthesis of the review findings: 'Nurses as information and communication
      facilitators', 'Nurses as family support providers', 'Nurses' non-supportive
      behaviours' and 'Improving nurses' communication skills'. CONCLUSIONS: Most ICU
      nurses considered communicating with families a vital part of their role, and
      described supportive behaviours. However, they perceived significant barriers to
      effective communication; some as a result of active decisions on their part, and
      some beyond their control. These barriers often resulted in nurses believing that
      families received suboptimal information and support. Peer support and formal
      training were identified as key strategies to overcome inadequacies. RELEVANCE TO
      CLINICAL PRACTICE: This review summarizes nurses' perceptions of the means and
      barriers for communicating with families in ICUs. Intensive care nurses need
      skills and knowledge in how to communicate effectively with families. This skill
      can be learnt formally, or acquired from role modelling of more experienced
      peers.

PMID- 25583407
TI  - The development of next-generation screening and diagnostic platforms will change
      diabetes care.
AB  - Diabetes mellitus is a common disease with a rising incidence and the findings of
      hyperglycemia and glucosuria. However, there are multiple types of diabetes, each
      with distinct etiologies. The two major types of diabetes are type 1, which is
      caused by an autoimmune process, and type 2, which is thought to be primarily
      metabolic, resulting from insulin resistance, often in the setting of obesity.
      Historically, the distinction between these two types was obvious. Here, we
      discuss how this paradigm has dramatically changed because of both the evolving
      epidemiology of diabetes mellitus and new and emerging tools, and therapies to
      diagnose and treat diabetes. As we believe that understanding these changes is
      critical to providing optimal care to patients with diabetes, we have developed a
      novel plasmonic gold chip platform that is able to meet the new and emerging
      demands of modern diabetes care. 

PMID- 25583408
TI  - Total synthesis of trioxacarcin DC-45-A2.
AB  - An enantioselective total synthesis of trioxacarcin DC-45-A2 (1) featuring a
      novel Lewis acid-induced cascade rearrangement of epoxyketone 6 to forge the
      polyoxygenated 2,7-dioxabicyclo[2.2.1]heptane core of the molecule is described. 

PMID- 25583406
TI  - Activation of villous trophoblastic p38 and ERK1/2 signaling pathways in preterm
      preeclampsia and HELLP syndrome.
AB  - Preterm preeclampsia is associated with the failure of trophoblast invasion,
      placental hypoxic/ischemic injury and the release of toxic substances, which
      promote the terminal pathway of preeclampsia. In term preeclampsia, factors yet
      unknown trigger the placenta to induce the terminal pathway. The contribution of
      the villous trophoblast to these pathologic events has not been fully elucidated.
      Here we aimed to study how stress and signaling pathways influence trophoblastic
      functions in various subforms of preeclampsia. Tissue microarrays (TMAs) were
      constructed from placentas obtained from pregnant women in the following groups:
      1-2) preterm preeclampsia with (n = 8) or without (n = 7) HELLP syndrome; 3) late
      onset preeclampsia (n = 8); 4-5) preterm (n = 5) and term (n = 9) controls. TMA
      slides were stained for phosphorylated Akt-1, ERK1/2, JNK, and p38 kinases, and
      trophoblastic immunostainings were semi-quantitatively evaluated. BeWo cells were
      kept in various stress conditions, and the expression of FLT1, GCM1, LEP, and PGF
      was profiled by qRT-PCR, while Akt-1, ERK1/2, JNK, and p38 kinase activities were
      measured with phospho-kinase immunoassays. We found that: 1) Placental LEP and
      FLT1 expression was up-regulated in preterm preeclampsia with or without HELLP
      syndrome compared to controls; 2) Mean pp38 immunoscore was higher in preterm
      preeclampsia, especially in cases with HELLP syndrome, than in controls. 3) Mean
      pERK1/2 immunoscore was higher in preterm preeclampsia with HELLP syndrome than
      in controls. 4) In BeWo cells, ischemia up-regulated LEP expression, and it
      increased JNK and decreased ERK1/2 activity. 5) Hypoxia up-regulated FLT1 and
      down-regulated PGF expression, and it increased ERK1/2, JNK and p38 activity. 6)
      IL-1beta treatment down-regulated PGF expression, and it increased JNK and p38
      activity. 7) The p38 signaling pathway had the most impact on LEP, FLT1 and PGF
      expression. In conclusion, hypoxic and ischemic stress, along with unknown
      factors, activates trophoblastic p38 signaling, which has a key role in villous
      trophoblastic functional changes in preterm preeclampsia. The activation of
      ERK1/2 signaling may induce additional trophoblastic functional changes in HELLP
      syndrome, while distinct mechanisms may promote late-onset preeclampsia.

PMID- 25583410
TI  - Plain silver surface plasmon resonance for microarray application.
AB  - The application scope of surface plasmon resonance (SPR) and SPR imaging (SPRi)
      is rapidly growing, and tools such as high-performance and low-cost slides could
      enable more rapid growth of the field. We describe herein a novel silver slide,
      addressing the inherent instability of plain silver structure by improving
      adhesion between the glass substrate and the silver layer with a thin buffer
      layer of gold. Covered by a self-assembled monolayer (SAM) only, SPR
      characteristics of the slide remain steady for more than 3 months under regular
      storage. In a bioassay, the slide substantiates the predicted nearly 100%
      sensitivity improvement over gold slides and exhibits exceptional performance
      stability as determined by sensitivity and resolution measurements during the
      extended 40,000 s multicycle experiment. We demonstrate the suitability of this
      new slide for large-area SPRi, describing analysis results from a 1 296-ligand
      protein microarray. We predict this slide structure will provide a stable, high
      sensitivity solution for high-throughput SPRi applications and other surface
      analysis platforms.

PMID- 25583411
TI  - Geometrical implication of ion transporters employing an ellipsoidal hollow
      structure in pseudo-solid electrolytes.
AB  - We demonstrate facilitated ion transport in oligomer electrolytes by introducing
      TiO2 hollow particles of ellipsoidal and spherical shapes. It was found that the
      TiO2 hollow particles of ellipsoidal shape are much more effective in
      constructing ionic diffusion paths for the Grotthuss mechanism, resulting in
      highly enhanced diffusion coefficients of ions such as I(-) and I3(-) in oligomer
      electrolytes. Compared to the hollow spheres of the TiO2 component, the
      ellipsoidal hollow particles of the TiO2 component provide 11% larger ionic
      diffusion coefficients, because of their geometry with a relatively small
      diffusion resistance. Since the facilitated ion transport can render fast redox
      reactions at both photo and counter electrodes, the solid state dye-sensitized
      solar cells employing oligomer electrolytes based on the TiO2 hollow ellipsoids
      exhibit highly improved photovoltaic performances including highly improved
      energy-conversion efficiency without destabilizing the cell. 

PMID- 25583409
TI  - The systemic influence of platelet-derived growth factors on bone marrow
      mesenchymal stem cells in fracture patients.
AB  - BACKGROUND: Fracture healing is a complex process regulated by a variety of cells
      and signalling molecules which act both locally and systemically. The aim of this
      study was to investigate potential changes in patients' mesenchymal stem cells
      (MSCs) in the iliac crest (IC) bone marrow (BM) and in peripheral blood (PB) in
      relation to the severity of trauma and to correlate them with systemic changes
      reflective of inflammatory and platelet responses following fracture. METHODS:
      ICBM samples were aspirated from two trauma groups: isolated trauma and
      polytrauma (n = 8 and 18, respectively) at two time-points post-fracture and from
      non-trauma controls (n = 7). Matched PB was collected every other day for a
      minimum of 14 days. BM MSCs were enumerated using colony forming-fibroblast (CFU
      F) assay and flow cytometry for the CD45-CD271+ phenotype. RESULTS: Regardless of
      the severity of trauma, no significant increase or decrease in BM MSCs was
      observed following fracture and MSCs were not mobilised into PB. However, direct
      positive correlations were observed between changes in the numbers of aspirated
      BM MSCs and time-matched changes in their serum PDGF-AA and -BB. In vitro,
      patients' serum induced MSC proliferation in a manner reflecting changes in
      PDGFs. PDGF receptors CD140a and CD140b were expressed on native CD45-CD271+ BM
      MSCs (average 12% and 64%, respectively) and changed over time in direct
      relationship with platelets/PDGFs. CONCLUSIONS: Platelet lysates and other
      platelet-derived products are used to expand MSCs ex vivo. This study
      demonstrates that endogenous PDGFs can influence MSC responses in vivo. This
      indicates a highly dynamic, rather than static, MSC nature in humans.

PMID- 25583412
TI  - Novel technologies can provide effective dressing and securement for peripheral
      arterial catheters: A pilot randomised controlled trial in the operating theatre
      and the intensive care unit.
AB  - BACKGROUND: Peripheral arterial catheters are widely used in the care of
      intensive care patients for continuous blood pressure monitoring and blood
      sampling, yet failure - from dislodgement, accidental removal, and complications
      of phlebitis, pain, occlusion and infection - is common. While appropriate
      methods of dressing and securement are required to reduce these complications
      that cause failure, few studies have been conducted in this area. OBJECTIVES: To
      determine initial effectiveness of one dressing and two securement methods versus
      usual care, in minimising failure in peripheral arterial catheters. Feasibility
      objectives were considered successful if 90/120 patients (75%) received the study
      intervention and protocol correctly, and had ease and satisfaction scores for the
      study dressing and securement devices of >= 7 on Numerical Rating Scale scores 1
      10. METHODS: In this single-site, four-arm, parallel, pilot randomised controlled
      trial, patients with arterial catheters, inserted in the operating theatre and
      admitted to the intensive care unit postoperatively, were randomly assigned to
      either one of the three treatment groups (bordered polyurethane dressing (n=30);
      a sutureless securement device (n=31); tissue adhesive (n=32)), or a control
      group (usual practice polyurethane dressing (not bordered) (n=30)). RESULTS: One
      hundred and twenty-three patients completed the trial. The primary outcome of
      catheter failure was 2/32 (6.3%) for tissue adhesive, 4/30 (13.3%) for bordered
      polyurethane, 5/31 (16.1%) for the sutureless securement device, and 6/30 (20%)
      for the control usual care polyurethane. Feasibility criteria were fulfilled.
      Cost analysis suggested that tissue adhesive was the most cost effective.
      CONCLUSIONS: The pilot trial showed that the novel technologies were at least as
      effective as the present method of a polyurethane dressing for dressing and
      securement of arterial catheters, and may be cost effective. The trial also
      provided evidence that a larger, multicentre trial would be feasible.

PMID- 25583413
TI  - [(68)Ga-PSMA as a new tracer for evaluation of prostate cancer: comparison
      between PET-CT and PET-MRI in biochemical recurrence].

PMID- 25583414
TI  - Poly(amino acid)-based fibrous scaffolds modified with surface-pendant peptides
      for cartilage tissue engineering.
AB  - In this study, fibrous scaffolds based on poly(gamma-benzyl-l-glutamate) (PBLG)
      were investigated in terms of the chondrogenic differentiation potential of human
      tooth germ stem cells (HTGSCs). Through the solution-assisted bonding of the
      fibres, fully connected scaffolds with pore sizes in the range 20-400 um were
      prepared. Biomimetic modification of the PBLG scaffolds was achieved by a two
      step reaction procedure: first, aminolysis of the PBLG fibres' surface layers was
      performed, which resulted in an increase in the hydrophilicity of the fibrous
      scaffolds after the introduction of N5 -hydroxyethyl-l-glutamine units; and
      second, modification with the short peptide sequence azidopentanoyl-GGGRGDSGGGY
      NH2 , using the 'click' reaction on the previously modified scaffold with 2
      propynyl side-chains, was performed. Radio-assay of the 125 I-labelled peptide
      was used to evaluate the RGD density in the fibrous scaffolds (which varied in
      the range 10-3 -10 pm/cm2 ). All the PBLG scaffolds, especially with density 90
      +/- 20 fm/cm2 and 200 +/- 100 fm/cm2 RGD, were found to be potentially suitable
      for growth and chondrogenic differentiation of HTGSCs. Copyright (c) 2015 John
      Wiley & Sons, Ltd.

PMID- 25583415
TI  - Clinical expression of patients with the D1152H CFTR mutation.
AB  - BACKGROUND: Discordant results were reported on the clinical expression of
      subjects bearing the D1152H CFTR mutation, and also for the small number of cases
      reported so far. METHODS: A retrospective review of clinical, genetic and
      biochemical data was performed from individuals homozygous or compound
      heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF)
      centers. RESULTS: 89 subjects carrying at least D1152H on one allele were
      identified. 7 homozygous patients had very mild clinical expression. Over half of
      the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation
      had borderline or pathological sweat test and respiratory or gastrointestinal
      symptoms; one third had pulmonary bacteria colonization and 10/74 cases had
      complications (i.e. diabetes, allergic bronchopulmonary aspergillosis, and
      hemoptysis). However, their clinical expression was less severe as compared to a
      group of CF patients homozygous for the F508del mutation. Finally, 8 subjects
      compound heterozygous for D1152H and a IV-V class mutation showed very mild
      disease. CONCLUSIONS: The natural history of subjects bearing the D1152H mutation
      is widely heterogeneous and is influenced by the mutation in trans.

PMID- 25583416
TI  - Mutation screening of the Kruppel-like factor 1 gene using single-strand
      conformational polymorphism in a cohort of Iranian beta-thalassemia patients.
AB  - The Kruppel-like factor 1 (KLF1) is an essential erythroid-specific transcription
      factor. Mutations in the human KLF1 gene have different phenotypic effects,
      ranging from increased Hb F levels to the disruption of erythropoiesis. Here, we
      screened 227 Iranian beta-thalassemia (beta-thal) patients for the presence of
      KLF1 mutations by using the single-strand conformational polymorphism (SSCP)
      approach. Our aim was to assess the potential effect of these mutations on the
      beta-thal disease severity. After screening, two variants were found. One patient
      carried a potentially deleterious variant (Polyphen-2) in exon 2 (p.F182L).
      Another patient was homozygous for a previously unreported intronic variant
      (KLF1: c.911 + 84A > G). The patient with the p.F182L variant (KLF1: c.544T > C)
      had noticeably high Hb A2 levels (7.6%), consistent with the phenotypic effect of
      several previously characterized KLF1 mutations in the same exonic region. In
      addition, he had higher platelet counts (1,069,000/MUL) compared to other
      patients in the cohort.

PMID- 25583418
TI  - [Vitreoretinal interface: pathophysiological, morphological and functional
      aspects].

PMID- 25583417
TI  - Effect of dopaminergic medication on speech dysfluency in Parkinson's disease: a
      longitudinal study.
AB  - Although speech dysfluencies have been hypothesized to be associated with
      abnormal function of dopaminergic system, the effects of dopaminergic medication
      on speech fluency in Parkinson's disease (PD) have not been systematically
      studied. The aim of the present study was, therefore, to investigate the long
      term effect of dopaminergic medication on speech fluency in PD. Fourteen de novo
      PD patients with no history of developmental stuttering and 14 age- and sex
      matched healthy controls (HC) were recruited. PD subjects were examined three
      times; before the initiation of dopaminergic treatment and twice in following 6
      years. The percentage of dysfluent words was calculated from reading passage and
      monolog. The amount of medication was expressed by cumulative doses of L-dopa
      equivalent. After 3-6 years of dopaminergic therapy, PD patients exhibited
      significantly more dysfluent events compared to healthy subjects as well as to
      their own speech performance before the introduction of dopaminergic therapy (p <
      0.05). In addition, we found a strong positive correlation between the increased
      occurrence of dysfluent words and the total cumulative dose of L-dopa equivalent
      (r = 0.75, p = 0.002). Our findings indicate an adverse effect of prolonged
      dopaminergic therapy contributing to the development of stuttering-like
      dysfluencies in PD. These findings may have important implication in clinical
      practice, where speech fluency should be taken into account to optimize
      dopaminergic therapy.

PMID- 25583419
TI  - Treatment and management of high-grade T1 bladder cancer: what should we do after
      second TUR?
AB  - Most T1 bladder cancers are high grade and have the potential to progress to
      muscle invasion and extravesical dissemination. Many studies reported that ~50%
      of patients displayed residual tumors when a second transurethral resection was
      performed 2-6 weeks after the initial resection for patients who were diagnosed
      with T1 bladder cancer. Furthermore, muscle-invasive disease was detected by the
      second transurethral resection in 10-25% of those patients. Therefore, a second
      transurethral resection is strongly recommended for patients newly diagnosed with
      high-grade T1 bladder cancer in various guidelines. T1 bladder cancers are
      heterogeneous in terms of progression and prognosis after the second
      transurethral resection. Optimal management and treatment should be considered
      for patients with T1 bladder cancer based on the pathological findings for the
      second transurethral resection specimen. If the second transurethral resection
      reveals residual tumors, aggressive treatments based on the pathological findings
      should be performed. Conversely, overtreatment with respect to the tumor status
      should be avoided. Since the evidence of pathological diagnosis at the second
      transurethral resection is insufficient and many retrospective studies were
      carried out before the second transurethral resection era, prospective randomized
      studies should be conducted.

PMID- 25583420
TI  - Relationship between smoking and multiple colorectal cancers in patients with
      Japanese Lynch syndrome: a cross-sectional study conducted by the Japanese
      Society for Cancer of the Colon and Rectum.
AB  - The positive correlation between smoking and cancer risk is well estimated in
      sporadic colorectal cancer, whereas little is known with regard to Lynch syndrome
      associated colorectal cancer. A total of 118 familial colorectal cancer patients
      from the Hereditary Nonpolyposis Colorectal Cancer Registry and Genetic Testing
      Project of the Japanese Society for Cancer of the Colon and Rectum, were assessed
      to determine whether smoking alters the incidence of multiple colorectal cancers.
      In male patients with Lynch syndrome (n = 29), the incidence of multiple
      colorectal cancers in patients who had ever smoked (smoking duration: median of
      19 years) was higher than that in those who never smoked (58.8% vs. 10.0%, P =
      0.02). The cumulative risk for metachronous colorectal cancer was significantly
      higher in male Lynch syndrome patients who had previously smoked than in those
      who had never smoked (P = 0.03). Our data suggest that long-term cigarette
      smoking might be a strong risk factor for the development of multiple colorectal
      cancers in male Lynch syndrome patients. 

PMID- 25583421
TI  - Progress and controversy for the role of chemotherapy in nasopharyngeal
      carcinoma.
AB  - Since the publication of Intergroup Study 0099, representing a superiority of
      concurrent chemoradiotherapy with cisplatin followed by adjuvant chemotherapy to
      radiotherapy alone for the treatment of locoregionally advanced nasopharyngeal
      carcinoma, an efficacy of concurrent setting of cisplatin-based chemotherapy with
      radiotherapy has been repeatedly validated. In meanwhile, the role of adjuvant
      part of the protocol has been controversial. There is an increasing evidence for
      the positive role of neoadjuvant chemotherapy with following concurrent
      chemoradiotherapy whereas favorable contribution was not proven in the last
      century. This article reviews the role of chemotherapy in the treatment of
      locoregionally advanced nasopharyngeal carcinoma. 

PMID- 25583422
TI  - Treatment possibilities of ipilimumab-induced thrombocytopenia--case study and
      literature review.
AB  - Recently, new drugs targeting the immune system have been introduced to the
      standard care of metastatic malignant melanoma. One of these immunomodulatory
      drugs is ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T
      lymphocyte antigen-4. The following case reports on a 54-year-old man with
      metastatic melanoma, who developed Grade 4 thrombocytopenia during treatment with
      ipilimumab already after first dose. Bone marrow examination confirmed a
      diagnosis of drug-induced, immune-mediated thrombocytopenia. Isolated
      thrombocytopenia has rarely been associated with ipilimumab and there is no
      standard treatment algorithm of such complication. This case demonstrates the
      importance of monitoring full blood count in all patients receiving ipilimumab
      and suggests a possible treatment algorithm. 

PMID- 25583423
TI  - Ovarian cancer: new developments in clear cell carcinoma and hopes for targeted
      therapy.
AB  - Until recently, ovarian clear cell carcinoma was recognized by its unique
      morphology and unfavorable patient outcome primarily due to tumor
      chemoresistance. Recently, specific molecular characteristics of ovarian clear
      cell carcinoma, such as PI3CA mutation, ARID1a mutation and MET amplification,
      have been elucidated. In addition, an association between endometriosis and the
      tumor has also been a focus of research in recent years. The aim of this review
      is to discuss the specificity and importance of molecular changes and various
      intriguing points that are not solved until today. Finally, future aspects,
      including hopes for the development of novel therapies, are discussed. 

PMID- 25583424
TI  - A survey about further work-up for cases with positive sputum cytology during
      lung cancer mass screening in Ishikawa Prefecture, Japan: a retrospective
      analysis about quality assurance of lung cancer screening.
AB  - OBJECTIVE: In cancer screening programs, performing appropriate further work-up
      is essential. In order to elucidate whether the further work-up for the subjects
      with positive screening results by sputum cytology was performed appropriately,
      the present study was conducted as the first large-scale thorough survey in
      Japan. METHODS: All of the lung cancer screening records from 2007 to 2012 in
      Ishikawa Prefecture were reviewed. Additional investigations about the further
      work-up were performed. RESULTS: In total, 2 234 984 people were invited to
      undergo lung cancer screening, and 494 424 people participated in the screening.
      Of these, 25 264 people underwent sputum cytology, and 68 positive cases were
      identified. Three of these 68 cases did not undergo further work-up, and another
      three cases had already been diagnosed to have lung cancer. Forty-five of the
      remaining 62 cases did not have suspicious chest shadows, and bronchoscopic
      examinations were performed in 36 cases. Seventeen of these 36 cases were
      diagnosed as having cancer, whereas none of the nine cases who did not receive
      the examination was diagnosed (P = 0.038). A bronchoscopic examination was not
      performed due to other medical conditions in three cases, due to the patient's
      refusal in another three cases and in the remaining three cases, the reasons were
      unknown. CONCLUSION: The participation rate for further work-up was very high.
      However, there are some issues to be resolved regarding the transmission of
      information. With our new registered hospital system, the quality assurance of
      our screening program will be improved.

PMID- 25583425
TI  - Relationship Between Empathy and Well-Being Among Emergency Nurses.
AB  - INTRODUCTION: A large number of patients who are in pain upon arriving at the
      emergency department are still in pain when they are discharged. It is suggested
      that nurses' personal traits and their level of empathy can explain in part this
      issue in pain management. The purpose of this study was to better understand the
      shortfalls in pain management provided by emergency nurses by considering nurses'
      characteristics. METHODS: A cross-sectional descriptive correlational design was
      used for this pilot study. French validated self-administrated questionnaires
      (sociodemographic characteristics, empathy, psychological distress, and well
      being) were presented to 40 emergency nurses. Thirty emergency nurses completed
      all questionnaires during work hours. Descriptive statistics, group comparisons,
      and correlation analyses were used for the data analysis. RESULTS: Emergency
      nurses appear to have low levels of empathy. High levels of psychological
      distress and low levels of well-being were also observed in our sample. Among
      these variables, only empathy and well-being appear to be related, because we
      found higher empathy scores in nurses with higher well-being. DISCUSSION: The
      poor mental health we found among emergency nurses is alarming. A clear need
      exists for supportive interventions for nurses. Finally, well-being was the only
      variable related to empathy. To our knowledge, this is the first study to report
      this relationship in nurses.

PMID- 25583426
TI  - Assessing Patient Decision-Making Capacity: It's About the Thought Process.

PMID- 25583427
TI  - Mitigating Nursing Biases in Management of Intoxicated and Suicidal Patients.

PMID- 25583428
TI  - [Who's afraid of open access? A growing, timely and necessary movement].

PMID- 25583429
TI  - Perceptions of School Among Childhood Cancer Survivors: A Comparison With Peers.
AB  - The aim was to investigate how childhood cancer survivors perceive school and
      whether their perceptions differ from corresponding descriptions of peers.
      Survivors (n = 48) currently attending educational institutions (median 5 years
      post diagnosis; now aged 12-21 years) from a national cohort of school-age
      children were compared with matched peers (n = 47). Data were collected through
      interviews and analyzed qualitatively and quantitatively. The results indicate
      that survivors and peers perceive school similarly; almost 90% described high
      well-being in school and indicated that they were motivated and received no
      additional tutoring; approximately 60% reported no difficulties achieving
      learning objectives. A few differences were found; survivors described themselves
      as more satisfied with their academic performance and school environment, but
      less satisfied with friends, than peers did. Previous treatment with radiation
      was associated with lower academic satisfaction among survivors. It is suggested
      that survivors perceive school overall as positive and do not have more problems
      reaching educational goals than their peers. However, quality of relationships
      with friends needs further investigation. 

PMID- 25583431
TI  - Nebulised adrenaline to manage a life-threatening complication in a pug with
      trismus.
AB  - A 13-month-old pug with severe trismus because of suspected masticatory muscle
      myositis underwent anaesthesia for magnetic resonance imaging. When regurgitation
      occurred, the tongue was pulled from the mouth to enable suctioning but could not
      be repositioned into the oral cavity as it was not possible to open the mouth.
      Swelling due to venous congestion and a bite wound were treated using nebulised
      adrenaline and resolved within 2 hours allowing retraction of the tongue. The use
      of nebulised adrenaline offers a non-invasive method of managing this potentially
      life-threatening complication. 

PMID- 25583430
TI  - Zinc-triggered hydrogelation of self-assembled small molecules to inhibit
      bacterial growth.
AB  - There is a significant need to develop antibacterial materials that could be
      applied locally and directly to the places surrounded by large amount of
      bacteria, in order to address the problems of bacterial antibiotic-resistance or
      irreversible biofilm formation. Hydrogels are thought to be suitable candidates
      due to their versatile applications in biomedical field. Among them, small
      molecular hydrogels have been paid lots of attention because they are easy to
      design and fabricate and often sensitive to external stimuli. Meanwhile, the
      antibacterial activity of metal ions are attracting more and more attention
      because resistance to them are not yet found within bacteria. We therefore
      designed the zinc ion binding peptide of Nap-GFFYGGGHGRGD, who can self-assemble
      into hydrogels after binds Zn(2+) and inhibit the growth of bacteria due to the
      excellent antibacterial activity of Zn(2+). Upon the addition of zinc ions,
      solutions containing Nap-GFFYGGGHGRGD transformed into supramolecular hydrogels
      composed of network of long nano-fibers. Bacterial tests revealed an
      antibacterial effect of the zinc triggered hydrogels on E. coli. The studied
      small molecular hydrogel shows great potential in locally addressing bacterial
      infections. 

PMID- 25583432
TI  - SAffold viruses in pediatric patients with diarrhea in Thailand.
AB  - Saffold virus (SAFV) is a newly discovered human virus which is classified into
      the genus Cardiovirus of the family Picornaviridae. A total of 608 fecal
      specimens collected during January 2012 to December 2013 from children with
      diarrhea in Chiang Mai, Thailand were investigated for SAFV by RT-nested PCR and
      sequence analysis. Of these, nine out of 608 (1.5%) were positive for SAFVs and
      four genotypes were identified, SAFV1, SAFV2, SAFV3, and SAFV4. SAFV mono
      infection was found in five cases (CMH-S038-12, CMH-S071-12, CMH-S102-12, CMH
      N029-12, and CMH-S048-13), while co-infection with other viruses causing diarrhea
      was observed in four cases (CMH-S021-12, CMH-S115-12, CMH-N048-13 and CMH-N103
      13). This study provides more information about the genetic background of SAFV
      circulating in pediatric patients with diarrhea in Thailand.

PMID- 25583434
TI  - High-yield production of highly conductive graphene via reversible covalent
      chemistry.
AB  - On the basis of the Diels-Alder reaction of graphite and tetracyanoethylene,
      graphite has been mechanically exfoliated into graphene adducts in a yield up to
      38%. The graphene adduct can restore its conjugated structure via retro-Diels
      Alder reaction under mild conditions, exhibiting a high conductivity of 1035 S m(
      1). 

PMID- 25583433
TI  - Trends in prevalence for moderate-to-severe pain and persistent pain among
      Medicare beneficiaries in nursing homes, 2006-2009.
AB  - BACKGROUND: Managing pain for the elderly is challenging due to their concurrent
      illnesses, underreport of pain, complex clinical manifestation of pain and higher
      chance of medication-related side effects. The objectives of this study were (a)
      to evaluate trends in annual prevalence of moderate-to-severe pain and persistent
      pain among Medicare beneficiaries residing in nursing homes; and (b) to identify
      resident and facility characteristics associated with persistent pain. METHODS:
      This was an observational study using linked data from 2006 to 2009 Medicare
      Current Beneficiary Survey and Minimum Data Set 2.0. Pain level was determined by
      a validated scale based on two items from Minimum Data Set 2.0 regarding
      frequency and intensity of pain. An episode of persistent pain was identified if
      moderate-to-severe pain reported at a Minimum Data Set 2.0 assessment was not
      alleviated at subsequent assessment. The Cochran-Armitage trend test was
      performed to detect trends in moderate-to-severe pain and persistent pain between
      2006 and 2009. Generalize linear models using generalized estimating equation
      were used to identify characteristics associated with persistent pain. RESULTS:
      Annual prevalence of moderate-to-severe pain consistently declined from 29.3% in
      2006 to 22.2% in 2009 (p < .01), while approximately 60% of beneficiaries
      experienced persistent pain annually (p = .50). Younger age, moderate initial
      pain, presence of diabetes, and skilled nursing home stays with assessments <21
      days apart were associated with higher risks for persistent pain. CONCLUSIONS:
      Annual prevalence of moderate-to-severe pain has consistently declined among
      Medicare Beneficiaries in nursing homes. However, resolution of pain among
      residents experiencing moderate-to-severe pain was still problematic.

PMID- 25583435
TI  - Order in the chaos: the secret of the large negative entropy of dissolving 1
      alkyl-3-methylimidazolium chloride in trihexyltetradecylphosphonium chloride.
AB  - The dissolution of 1-alkyl-3-methylimidazolium chloride ILs with short alkyl
      chains in trihexyltetradecylphosphonium chloride does not only exhibit a large
      negative entropy. Also, in the resulting mixtures, the phosphonium cation
      diffuses faster than the much smaller imidazolium cation. Both unexpected
      features originate from the formation of a large symmetric ion cluster cage in
      which the imidazolium cation is caught by three chloride anions and four
      phosphonium cations. 

PMID- 25583437
TI  - Noscapine comes of age.
AB  - Noscapine is a phthalideisoquinoline alkaloid, which represents a class of plant
      specialized metabolites within the large and structurally diverse group of
      benzylisoquinoline alkaloids. Along with the narcotic analgesic morphine,
      noscapine is a major alkaloid in the latex of opium poppy (Papaver somniferum)
      that has long been used as a cough suppressant and has undergone extensive
      investigation as a potential anticancer drug. Cultivated opium poppy plants
      remain the only commercial source of noscapine. Despite its isolation from opium
      more than two centuries ago, the almost complete biosynthesis of noscapine has
      only recently been established based on an impressive combination of molecular
      genetics, functional genomics, and metabolic biochemistry. In this review, we
      provide a historical account of noscapine from its discovery through to initial
      investigations of its formation in opium poppy. We also describe recent
      breakthroughs that have led to an elucidation of the noscapine biosynthetic
      pathway, and we discuss the pharmacological properties that have prompted
      intensive evaluation of the potential pharmaceutical applications of noscapine
      and several semi-synthetic derivatives. Finally, we speculate on the future
      potential for the production of noscapine using metabolic engineering and
      synthetic biology in plants and microbes. 

PMID- 25583436
TI  - Current trends in surgical approach and outcomes following pituitary tumor
      resection.
AB  - OBJECTIVES/HYPOTHESIS: The goals of pituitary tumor resection include normalizing
      endocrine function, relieving mass effect, and minimizing risk of recurrence.
      This study investigated current trends in costs and complications for
      transfrontal and transsphenoidal pituitary surgery. STUDY DESIGN: Retrospective
      review of the 2008-2011 Nationwide Inpatient Sample for patients undergoing
      pituitary lesion resection. METHODS: Demographics and outcomes were compared
      between transfrontal and transsphenoidal surgical approaches using chi(2) tests.
      Multivariate analysis was performed to investigate outcomes while controlling for
      confounders. RESULTS: There were 8,543 admissions for resection of pituitary
      lesions that met our inclusion criteria. Most (>90%) were treated
      transsphenoidally. The transfrontal approach was most frequent in the young (<35
      years) and in the South. Rates of mortality and complications were higher in
      patients undergoing transfrontal surgery. Multivariate analysis found
      transsphenoidal resection was associated with a reduction in hospital costs and
      length of stay by over 50%; low-volume hospitals had increased cost and length of
      stay. There was an increased rate of transfrontal approaches at low-volume
      centers. CONCLUSIONS: Multiple factors influence outcomes of pituitary tumor
      resection. Transsphenoidal pituitary surgery is associated with a shorter length
      of stay, lower cost, and lower complication rates when compared to transfrontal
      surgery. Case specifics, including tumor location and size, influence approach
      and lead to a selection bias that cannot be controlled for in the present study.
      The prevalence of transfrontal resections at low-volume centers may indicate an
      area of further investigation. Additionally, when controlling for surgical
      approach, low-volume centers were found to adversely affect economic outcomes and
      also warrants investigation. LEVEL OF EVIDENCE: 2c.

PMID- 25583438
TI  - Isolation and SAR studies of bicyclic iminosugars from Castanospermum australe as
      glycosidase inhibitors.
AB  - We report the isolation and structural determination of fourteen iminosugars,
      containing five pyrrolizidines and five indolizidines, from Castanospermum
      australe. The structure of a new alkaloid was elucidated by spectroscopic methods
      as 6,8-diepi-castanospermine (13). Our side-by-side comparison between bicyclic
      and corresponding monocyclic iminosugars revealed that inhibition potency and
      spectrum against each enzyme are clearly changed by their core structures.
      Castanospermine (10) and 1-deoxynojirimycin (DNJ) have a common d-gluco
      configuration, and they showed the expected similar inhibition potency and
      spectrum. In sharp contrast, 6-epi-castanospermine (12) and 1-deoxymannojirimycin
      (manno-DNJ) both have the d-manno configuration but the alpha-mannosidase
      inhibition of 6-epi-castanospermine (12) was much better than that of manno-DNJ.
      6,8-Diepi-castanospermine (13) could be regarded as a bicyclic derivative of talo
      DNJ, but it showed a complete loss of alpha-galactosidase A inhibition. This
      behavior against alpha-galactosidase A is similar to that observed for 1-epi
      australine (6) and altro-DMDP. 

PMID- 25583439
TI  - Indole-3-acetic acid (IAA) induced changes in oil content, fatty acid profiles
      and expression of four fatty acid biosynthetic genes in Chlorella vulgaris at
      early stationary growth phase.
AB  - Microalgae lipids and oils are potential candidates for renewable biodiesel. Many
      microalgae species accumulate a substantial amount of lipids and oils under
      environmental stresses. However, low growth rate under these adverse conditions
      account for the decrease in overall biomass productivity which directly influence
      the oil yield. This study was undertaken to investigate the effect of exogenously
      added auxin (indole-3-acetic acid; IAA) on the oil content, fatty acid
      compositions, and the expression of fatty acid biosynthetic genes in Chlorella
      vulgaris (UMT-M1). Auxin has been shown to regulate growth and metabolite
      production of several microalgae. Results showed that oil accumulation was
      highest on days after treatment (DAT)-2 with enriched levels of palmitic (C16:0)
      and stearic (C18:0) acids, while the linoleic (C18:2) and alpha-linolenic
      (C18:3n3) acids levels were markedly reduced by IAA. The elevated levels of
      saturated fatty acids (C16:0 and C18:0) were consistent with high expression of
      the beta-ketoacyl ACP synthase I (KAS I) gene, while low expression of omega-6
      fatty acid desaturase (omega-6 FAD) gene was consistent with low production of
      C18:2. However, the increment of stearoyl-ACP desaturase (SAD) gene expression
      upon IAA induction did not coincide with oleic acid (C18:1) production. The
      expression of omega-3 fatty acid desaturase (omega-3 FAD) gene showed a positive
      correlation with the synthesis of PUFA and C18:3n3. 

PMID- 25583440
TI  - The value of the combination of fibrosis index based on the four factors and
      future liver remnant volume ratios as a predictor on posthepatectomy outcomes.
AB  - BACKGROUND: Liver fibrosis and cirrhosis are well-known risk factors for
      morbidity and mortality after hepatectomy. Fibrosis index based on the four
      factors (FIB-4) is a non-invasive method for detection of hepatic fibrosis and
      cirrhosis with high accuracy. This study aimed to evaluate the predictive value
      of future liver remnant volume ratios (FLRVR)/FIB-4 after liver resection for
      posthepatectomy outcomes in patients with fibrosis and cirrhosis. METHODS: All
      patients with severe fibrosis or cirrhosis who underwent a liver resection (>=2
      segments) were included. Liver insufficiency was defined according to grade C
      posthepatectomy liver failure (PLF) proposed by the International Study Group of
      Liver Surgery (ISGLS). Receiver operating characteristic curves and logistic
      regression model were used to determine the optimal cutoff of FLRVR/FIB-4 and
      independent risk factors of postoperative outcomes. RESULTS: The study population
      consisted of 338 patients. FLRVR/FIB-4 was gradually correlated with short-term
      outcomes. The optimal value of FLRVR/FIB-4 to predict PLF was 0.13 when
      considering grade C PLF and postoperative death. A value of 0.24 best predicted
      postoperative morbidity. At multivariate analysis, FLRVR/FIB-4 remained an
      independent predictor of PLF (risk ratio(RR) = 0.046; 95% confidence interval
      (CI): 0.010-0.215; P < 0.001), postoperative morbidity (RR = 0.272; 95% CI: 0.167
      0.445; P < 0.001) and mortality(RR =0.058; 95% CI: 0.012-0.277; P < 0.001).
      CONCLUSION: FLRVR/FIB-4 is an independent predictive factor of postoperative
      outcomes after liver resection in patients with cirrhosis. It is a useful
      preoperative investigation for risk stratification before hepatectomy.

PMID- 25583441
TI  - Osteopontin (OPN) isoforms, diabetes, obesity, and cancer; what is one got to do
      with the other? A new role for OPN.
AB  - Alternative splicing of osteopontin (OPN) produces three isoforms: OPNa, OPNb,
      and OPNc. The aims of this study were to examine the expression profile of OPN
      isoforms in sera from patients with pancreatic lesions and to determine their
      correlation with the presence of comorbid systemic inflammatory conditions, such
      as diabetes and/or obesity. Sera from 90 patients undergoing pancreatic surgery
      and 29 healthy volunteers were analyzed. Seventeen patients were diabetics, 17
      were obese, and 6 had both diabetes and obesity. In patients with pancreatic
      lesions, OPNb was expressed in 48% of the patients' sera, OPNc in 34%, and both
      in 5%. The presence of diabetes and/or obesity was associated with complete
      disappearance of OPNb and expression of only OPNc. OPNc presence was
      significantly associated with diabetes and obesity (OR = 7.06 [95% CI 1.97-23.3];
      p = 0.003). No OPNb or OPNc was detected in the normal sera. Overexpression of
      OPNb and OPNc isoforms in PDA cells significantly (p < 0.05) increased their
      activity in soft-agar colony formation and wound healing assays, induced the
      transcription of interleukin (IL)-6, and reduced tumor necrosis factor alpha (TNF
      alpha), interferon gamma (IFN-gamma), and IL-10. Our data show for the first time
      the significant association between serum OPNc and diabetes and/or obesity.
      Unraveling the functional role of OPN isoforms in systemic inflammation is
      essential to understanding their significance as therapeutic targets in diabetes
      and obesity, and during metastasis development in PDA.

PMID- 25583442
TI  - Diurnal variation in skeletal muscle and liver glycogen in humans with normal
      health and Type 2 diabetes.
AB  - In health, food carbohydrate is stored as glycogen in muscle and liver,
      preventing a deleterious rise in osmotically active plasma glucose after eating.
      Glycogen concentrations increase sequentially after each meal to peak in the
      evening, and fall to fasting levels thereafter. Skeletal muscle accounts for the
      larger part of this diurnal buffering capacity with liver also contributing. The
      effectiveness of this diurnal mechanism has not been previously studied in Type 2
      diabetes. We have quantified the changes in muscle and liver glycogen
      concentration with 13C magnetic resonance spectroscopy at 3.0 T before and after
      three meals consumed at 4 h intervals. We studied 40 (25 males; 15 females) well
      controlled Type 2 diabetes subjects on metformin only (HbA1c (glycated
      haemoglobin) 6.4+/-0.07% or 47+/-0.8 mmol/mol) and 14 (8 males; 6 females)
      glucose-tolerant controls matched for age, weight and body mass index (BMI).
      Muscle glycogen concentration increased by 17% after day-long eating in the
      control group (68.1+/-4.8 to 79.7+/-4.2 mmol/l; P=0.006), and this change
      inversely correlated with homoeostatic model assessment of insulin resistance
      [HOMA-IR] (r=-0.56; P=0.02). There was no change in muscle glycogen in the Type 2
      diabetes group after day-long eating (68.3+/-2.6 to 67.1+/-2.0 mmol/mol; P=0.62).
      Liver glycogen rose similarly in normal control (325.9+/-25.0 to 388.1+/-30.3
      mmol/l; P=0.005) and Type 2 diabetes groups (296.1+/-16.0 to 350.5+/-6.7 mmol/l;
      P<0.0001). In early Type 2 diabetes, the major physiological mechanism for
      skeletal muscle postprandial glycogen storage is completely inactive. This is
      directly related to insulin resistance, although liver glycogen storage is
      normal. 

PMID- 25583443
TI  - A pharmacokinetic model for quantifying the effect of vascular permeability on
      the choice of drug carrier: a framework for personalized nanomedicine.
AB  - Drug carriers in the ~ 100 nm size range are of considerable interest in the
      field of cancer therapy because of their ability to passively accumulate in
      tumors. Tailoring the physicochemical properties of these carriers to individual
      patient requirements will help exploit their full therapeutic potential. Here, we
      present a pharmacokinetic model to explain how vascular physiology could be used
      to guide the optimal choice of specific formulation parameters. We find that in
      order to maximize the benefit-to-risk ratio, nanosystems should be confined to a
      specific particle size range. The optimal particle size range is dictated by the
      vascular pore size of not only the tumor tissue but also of the normal organs.
      Additionally, the duration of drug release is a key variable that can be used to
      maximize the therapeutic benefit of nanomedicine. Our model further suggests that
      the enhanced permeability and retention effect is not necessarily a universal
      outcome for every nanocarrier in every tumor model but will only be observed for
      nanoparticles of a specific size range. This optimal size range, in turn, is
      governed by the vascular physiology of the tumor and of non-target organs.

PMID- 25583444
TI  - Intermediate-conductance calcium-activated potassium channel KCa3.1 and chloride
      channel modulate chemokine ligand (CCL19/CCL21)-induced migration of dendritic
      cells.
AB  - The role of ion channels is largely unknown in chemokine-induced migration in
      nonexcitable cells such as dendritic cells (DCs). Here, we examined the role of
      intermediate-conductance calcium-activated potassium channel (KCa3.1) and
      chloride channel (CLC3) in lymphatic chemokine-induced migration of DCs. The
      amplitude and kinetics of chemokine ligand (CCL19/CCL21)-induced Ca(2+) influx
      were associated with chemokine receptor 7 expression levels, extracellular-free
      Ca(2+) and Cl(-), and independent of extracellular K(+). Chemokines (CCL19 and
      CCL21) and KCa3.1 activator (1-ethyl-1,3-dihydro-2H-benzimidazol-2-one) induced
      plasma membrane hyperpolarization and K(+) efflux, which was blocked by 1-[(2
      chlorophenyl)diphenylmethyl]-1H-pyrazole, suggesting that KCa3.1 carried larger
      conductance than the inward calcium release-activated calcium channel. Blockade
      of KCa3.1, low Cl(-) in the medium, and low dose of 4,4'-diisothiocyano-2,2'
      stilbenedisulfonic acid (DIDS) impaired CCL19/CCL21-induced Ca(2+) influx, cell
      volume change, and DC migration. High doses of DIDS completely blocked DC
      migration possibly by significantly disrupting mitochondrial membrane potential.
      In conclusion, KCa3.1 and CLC3 are critical in human DC migration by
      synergistically regulating membrane potential, chemokine-induced Ca(2+) influx,
      and cell volume. 

PMID- 25583446
TI  - Recent worldwide expansion of Nosema ceranae (Microsporidia) in Apis mellifera
      populations inferred from multilocus patterns of genetic variation.
AB  - Nosema ceranae has been found infecting Apismellifera colonies with increasing
      frequency and it now represents a major threat to the health and long-term
      survival of these honeybees worldwide. However, so far little is known about the
      population genetics of this parasite. Here, we describe the patterns of genetic
      variation at three genomic loci in a collection of isolates from all over the
      world. Our main findings are: (i) the levels of genetic polymorphism (piS~1%) do
      not vary significantly across its distribution range, (ii) there is substantial
      evidence for recombination among haplotypes, (iii) the best part of the observed
      genetic variance corresponds to differences within bee colonies (up to 88% of the
      total variance), (iv) parasites collected from Asian honeybees (Apis cerana and
      Apis florea) display significant differentiation from those obtained from
      Apismellifera (8-16% of the total variance, p<0.01) and (v) there is a
      significant excess of low frequency variants over neutral expectations among
      samples obtained from A. mellifera, but not from Asian honeybees. Overall these
      results are consistent with a recent colonization and rapid expansion of N.
      ceranae throughout A. mellifera colonies. 

PMID- 25583445
TI  - High incidence of monozygotic twinning after assisted reproduction is related to
      genetic information, but not to assisted reproduction technology itself.
AB  - OBJECTIVE: To study the incidence of monozygotic twinning (MZT) in patients using
      in vitro fertilization, relative to their age, genetic background, ovarian
      function, and assisted reproductive techniques used. DESIGN: Analysis of a
      collected database. SETTING: Infertility treatment center. PATIENT(S): A total of
      1,876 patients receiving infertility treatment between 2000 and 2012. Pregnancies
      with monozygotic twins (A: 23) were compared with deliveries of dizygotic twins
      (B: 423), singleton pregnancies (C: 880), and aborted pregnancies (D: 389).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A genetic survey on multiple
      pregnancies in the extended family. Measures were micromanipulation technique,
      the length of embryo cultivation, type of cultivation media, basal follicle
      stimulating hormone level, estradiol level on the day of human chorionic
      gonadotropin administration, number of oocytes, total consumption of
      gonadotropins, and consumption of gonadotropins needed for recovery of 1 oocyte.
      RESULT(S): No differences were found between the incidence of MZT in cycles that
      did vs. did not use micromanipulation techniques. In addition, the length of
      embryo cultivation or type of cultivation media used did not affect the results.
      Estradiol levels and implantation rates were significantly higher in group A. The
      incidence of MZT in families in group A was significantly higher than that in
      groups B and C. CONCLUSION(S): We propose that the high incidence of MZT in
      infertility-clinic patients is conditioned by hereditary factors, and good
      ovarian function only facilitates the expression. The resulting recommendation is
      that young women with a positive family history and good ovarian function undergo
      elective single-embryo transfer, and proper counseling is advisable.

PMID- 25583447
TI  - Characterisation of a diverse range of circular replication-associated protein
      encoding DNA viruses recovered from a sewage treatment oxidation pond.
AB  - Our knowledge of circular replication-associated protein encoding single-stranded
      (CRESS) DNA virus diversity has increased dramatically in recent years, largely
      due to advances in high-throughput sequencing technologies. These viruses are
      apparently major virome components in most terrestrial and aquatic environments
      and it is therefore of interest to determine their diversity at the interfaces
      between these environments. Treated sewage water is a particularly interesting
      interface between terrestrial and aquatic viromes in that it is directly pumped
      into waterways and is likely to contain virus populations that have been strongly
      impacted by humans. We used a combination of high-throughput sequencing, full
      genome PCR amplification, cloning and Sanger sequencing to investigate the
      diversity of CRESS DNA viruses present in a sewage oxidation pond. Using this
      approach, we recovered 50 putatively complete novel CRESS viral genomes (it
      remains possible that some are components of multipartite viral genomes) and 11
      putatively sub-genome-length circular DNA molecules which may be either defective
      genomes or components of multipartite genomes. Thirteen of the genomes have
      bidirectional genome organisations and share similar conserved replication
      associated protein (Rep) motifs to those of the gemycircularviruses: a group that
      in turn is most closely related to the geminiviruses. The remaining 37 viral
      genomes share very low degrees of Rep similarity to those of all other known
      CRESS DNA viruses. This number of highly divergent CRESS DNA virus genomes within
      a single sewage treatment pond further reinforces the notion that there likely
      exist hundreds of completely unknown genus/family level CRESS DNA virus
      groupings. 

PMID- 25583449
TI  - Application of microRNA gene resources in the improvement of agronomic traits in
      rice.
AB  - microRNAs (miRNAs) are important nonprotein-coding genes that are involved in
      almost all biological processes, including cell differentiation and fate
      determination, developmental regulation, and immune responses. Investigations
      have shown that some miRNAs can highly affect plant agricultural traits,
      including virus resistance, nematode resistance, drought and salinity tolerance,
      heavy metal detoxification, biomass yield, grain yield, fruit development and
      flower development. Therefore, these miRNAs are considered a newly identified
      gene resource for the genetic improvement of crops. In this review, we will
      summarize the recent findings of the rice miRNA-directed regulatory network,
      which controls agronomic traits such as yield, quality and stress tolerance, and
      explore the outlook for the uses of these miRNA-associated traits in rice
      biotechnology. 

PMID- 25583448
TI  - De novo assembly of bacterial transcriptomes from RNA-seq data.
AB  - Transcriptome assays are increasingly being performed by high-throughput RNA
      sequencing (RNA-seq). For organisms whose genomes have not been sequenced and
      annotated, transcriptomes must be assembled de novo from the RNA-seq data. Here,
      we present novel algorithms, specific to bacterial gene structures and
      transcriptomes, for analysis of bacterial RNA-seq data and de novo transcriptome
      assembly. The algorithms are implemented in an open source software system called
      Rockhopper 2. We find that Rockhopper 2 outperforms other de novo transcriptome
      assemblers and offers accurate and efficient analysis of bacterial RNA-seq data.
      Rockhopper 2 is available at http://cs.wellesley.edu/~btjaden/Rockhopper . 

PMID- 25583450
TI  - Observation of strong electron pairing on bands without Fermi surfaces in LiFe(1
      x)CoxAs.
AB  - In conventional BCS superconductors, the quantum condensation of superconducting
      electron pairs is understood as a Fermi surface instability, in which the low
      energy electrons are paired by attractive interactions. Whether this explanation
      is still valid in high-Tc superconductors such as cuprates and iron-based
      superconductors remains an open question. In particular, a fundamentally
      different picture of the electron pairs, which are believed to be formed locally
      by repulsive interactions, may prevail. Here we report a high-resolution angle
      resolved photoemission spectroscopy study on LiFe(1-x)CoxAs. We reveal a large
      and robust superconducting gap on a band sinking below the Fermi level on Co
      substitution. The observed Fermi-surface-free superconducting order is also the
      largest over the momentum space, which rules out a proximity effect origin and
      indicates that the order parameter is not tied to the Fermi surface as a result
      of a surface instability.

PMID- 25583451
TI  - Clinical usefulness of Mohs' chemosurgery for palliative purposes in patients
      with cutaneous squamous cell carcinoma with risk factors or without indication
      for surgery: three case reports.
AB  - Mohs' chemosurgery is a technique of chemical fixation of a cutaneous tumor using
      20% zinc chloride, and the surgeon performs a sequential series of excisions
      until no residual tumor can be found in the bottom layer of the specimen by
      microscopic examination. This technique has also been gradually accepted as one
      of the palliative treatment options in patients with cutaneous tumors with risk
      factors for surgery. We report three cases of cutaneous squamous cell carcinoma
      that were treated with Mohs' chemosurgery for palliative purposes. In case 1,
      Mohs' chemosurgery could prevent rapid tumor growth and control the bleeding,
      exudation and offensive odor from ulcerated tumors. The patient was able to live
      enjoyably at home with her family before she was transferred to a palliative care
      hospital. In case 2, Mohs' chemosurgery followed by debridement of residual tumor
      and a full-thickness skin graft contributed to an early hospital discharge, which
      prevented the progression of cognitive decline. In case 3, remission of the tumor
      was achieved by concurrent treatment with local radiotherapy and Mohs'
      chemosurgery. Mohs' chemosurgery for palliative purposes is not a radical
      treatment, but contributes to the patient's quality of life. It has the
      possibility of becoming a radical treatment if eligible patients and concurrent
      treatment are carefully selected. An increase in the number of skin cancer
      patients with risk factors for surgery has been predicted because of the
      progression of the aging society. Mohs' chemosurgery may become one of the
      treatment options for such patients. 

PMID- 25583453
TI  - Back to the real world: connecting models with data.
AB  - Mathematical models for infectious disease are often used to improve our
      understanding of infection biology or to evaluate the potential efficacy of
      intervention programs. Here, we develop a mathematical model that aims to
      describe infection dynamics of Mycobacterium avium subspecies paratuberculosis
      (MAP). The model was developed using current knowledge of infection biology and
      also includes some components of MAP infection dynamics that are currently still
      hypothetical. The objective was to show methods for parameter estimation of state
      transition models and to connect simulation models with detailed real life data.
      Thereby making model predictions and results of simulations more reflective and
      predictive of real world situations. Longitudinal field data from a large
      observational study are used to estimate parameter values. It is shown that
      precise data, including molecular diagnostics on the obtained MAP strains,
      results in more precise and realistic parameter estimates. It is argued that
      modeling of infection disease dynamics is of great value to understand the patho
      biology, epidemiology and control of infectious diseases. The quality of
      conclusions drawn from model studies depend on two key issues; first, the quality
      of biology that has gone in the process of developing the model structure; second
      the quality of the data that go into the estimation of the parameters and the
      quality and quantity of the data that go into model validation. The more real
      world data that are used in the model building process, the more likely that
      modeling studies will provide novel, innovative and valid results. 

PMID- 25583452
TI  - Restriction Cascade Exponential Amplification (RCEA) assay with an attomolar
      detection limit: a novel, highly specific, isothermal alternative to qPCR.
AB  - An alternative to qPCR was developed for nucleic acid assays, involving signal
      rather than target amplification. The new technology, Restriction Cascade
      Exponential Amplification (RCEA), relies on specific cleavage of probe-target
      hybrids by restriction endonucleases (REase). Two mutant REases for amplification
      (Ramp), S17C BamHI and K249C EcoRI, were conjugated to oligonucleotides, and
      immobilized on a solid surface. The signal generation was based on: (i)
      hybridization of a target DNA to a Ramp-oligonucleotide probe conjugate, followed
      by (ii) specific cleavage of the probe-target hybrid using a non-immobilized
      recognition REase. The amount of Ramp released into solution upon cleavage was
      proportionate to the DNA target amount. Signal amplification was achieved through
      catalysis, by the free Ramp, of a restriction cascade containing additional
      oligonucleotide-conjugated Ramp and horseradish peroxidase (HRP). Colorimetric
      quantification of free HRP indicated that the RCEA achieved a detection limit of
      10 aM (10(-17) M) target concentration, or approximately 200 molecules,
      comparable to the sensitivity of qPCR-based assays. The RCEA assay had high
      specificity, it was insensitive to non-specific binding, and detected target
      sequences in the presence of foreign DNA. RCEA is an inexpensive isothermal assay
      that allows coupling of the restriction cascade signal amplification with any DNA
      target of interest. 

PMID- 25583454
TI  - A domain dictionary of trimeric autotransporter adhesins.
AB  - Trimeric autotransporter adhesins (TAAs) are modular, highly repetitive outer
      membrane proteins that mediate adhesion to external surfaces in many Gram
      negative bacteria. In recent years, several TAAs have been investigated in
      considerable detail, also at the structural level. However, in their vast
      majority, putative TAAs in prokaryotic genomes remain poorly annotated, due to
      their sequence diversity and changeable domain architecture. In order to achieve
      an automated annotation of these proteins that is both detailed and accurate we
      have taken a domain dictionary approach, in which we identify recurrent domains
      by sequence comparisons, produce bioinformatic descriptors for each domain type,
      and connect these to structural information where available. We implemented this
      approach in a web-based platform, daTAA, in 2008 and demonstrated its
      applicability by reconstructing the complete fiber structure of a TAA conserved
      in enterobacteria. Here we review current knowledge on the domain structure of
      TAAs. 

PMID- 25583455
TI  - Bacterial cell wall research in Tubingen: a brief historical account.
AB  - Research in Tubingen on bacterial cell walls began in 1951 and continues to this
      day. The studies over the decades reflect the development in the field, which was
      strongly influenced by the design of suitable biochemical and genetic methods
      used to unravel the highly complex envelope structure. At the beginning of this
      period, improper crude extraction and solubilization methods were employed in an
      attempt to isolate pure components. Nevertheless, progress was steady and
      culminated in major insights into the structure and function of individual cell
      wall components and the cell wall as a whole. The "cell wall" has various
      definitions. In this short overview, the term includes the cell wall of gram
      positive bacteria in the strict sense, and also the outer membrane, the murein
      (peptidoglycan) and the outer membrane of gram-negative bacteria and the
      cytoplasmic membranes. 

PMID- 25583456
TI  - Incidence of an anatomically separate carcinoma of the breast in patients
      diagnosed with a papillary lesion on breast core biopsy.

PMID- 25583457
TI  - Characterisation of the efficacy of endodontic medications using a three
      dimensional fluorescent tooth model: An ex vivo study.
AB  - The purpose of this study was to establish a three-dimensional fluorescent tooth
      model to investigate bacterial viability against intra-canal medicaments across
      the thickness and surface of root dentine. Dental microbial biofilms
      (Enterococcus faecalis and Streptococcus mutans) were established on the external
      root surface and bacterial kill was monitored over time against intra-canal
      medicament (Ca(OH)2 ) using fluorescent microscopy in conjunction with BacLight
      SYTO9 and propidium iodide stains. An Olympus digital camera fitted to SZX16
      fluorescent microscope captured images of bacterial cells in biofilms on the
      external root surface. Viability of biofilm was measured by calculating the total
      pixel area of green (viable bacteria) and red (non-viable bacteria) for each
      image using ImageJ(r) software. All data generated were assessed for normality
      and then analysed using a Mann-Whitney t-test. The viability of S. mutans biofilm
      following Ca(OH)2 treatment showed a significant decline compared with the
      untreated group (P = 0.0418). No significant difference was seen for E. faecalis
      biofilm between the Ca(OH)2 and untreated groups indicating Ca(OH)2 medicament is
      ineffective against E. faecalis biofilm. This novel three-dimensional fluorescent
      biofilm model provides a new clinically relevant tool for testing of medicaments
      against dental biofilms. 

PMID- 25583458
TI  - Video endoscopic inguinal lymphadenectomy for lymph node metastasis from solid
      tumors.
AB  - AIM: Inguinal lymphadenectomy (IL) is the standard treatment for inguinal lymph
      node (LN) metastases from genitourinary neoplasm and other cutaneous
      malignancies. Video endoscopic inguinal lymphadenectomy (VEIL) is emerging as a
      new modality for treating inguinal LN metastasis, with the aim of reducing post
      operative complications. However, the safety and effectiveness of this new
      approach is still unclear. METHOD: A systematic literature review was performed.
      Patient characteristics, selection criteria, intra-operative data, number of
      excised LNs and post-operative outcomes were extracted and described for each
      study. RESULTS: Ten series that encompassed data of 236 procedures performed in
      168 patients were reviewed. The conversion to traditional IL rates ranged between
      0 and 7.7%. Median/mean operation time varied between 60 and 245 min. Wound
      related complications and lymphatic collection/seroma ranged between 0 and 13.3%
      and 4 and 38.4%, respectively. The median/mean number of excised inguinal LNs
      ranged between 7 and 16. Although only four studies reported a follow-up time
      longer then 2 years, local recurrence rate was up to 6.6%. CONCLUSIONS: VEIL is
      safe and feasible for experienced surgeons with advanced laparoscopic skills and
      familiarity with groin anatomy. The post-operative morbidity appears lower
      compared to the open procedure, mainly for wound/skin related complications. The
      number of harvested LN and the regional recurrence rate is comparable to that of
      conventional groin dissection. Before VEIL technique can be considered suitable
      for routine clinical practice, comparable oncological outcomes and lower post
      operative morbidity should be assessed in a randomized controlled trial.

PMID- 25583460
TI  - Reply: To PMID 24942598.

PMID- 25583459
TI  - A snapshot of nephron-sparing surgery in Italy: a prospective, multicenter report
      on clinical and perioperative outcomes (the RECORd 1 project).
AB  - INTRODUCTION: Nephron-sparing surgery (NSS) has become the standard of care for
      the surgical management of small and clinically localized renal cell carcinoma
      (RCC). The conservative management of those RCCs is increasing over time. Aim of
      this study was to report a snapshot of the clinical, perioperative and
      oncological results after NSS for RCC in Italy. MATERIAL AND METHODS: We
      evaluated all patients who underwent conservative surgical treatment for renal
      tumours between January 2009 and December 2012 at 19 urological Italian Centers
      (RECORd project). Perioperative, radiological and histopathological data were
      recorded. Surgical eras (2009 vs 2012 and year periods 2009-2010 vs 2011-2012)
      were compared. RESULTS: Globally, 983 patients were evaluated. More recently,
      patients undergoing NSS were found to be significantly younger (p = 0.05) than
      those surgically treated in the first study period, with a significantly higher
      rate of NSS with relative and imperative indication (p < 0.001). More recently, a
      higher percentage of procedures for cT1b or cT2 renal tumours was observed (p =
      0.02). Utilization rate of open partial nephrectomy (OPN) constantly decreased
      during years, laparoscopic partial nephrectomy (LPN) remained almost constant
      while robot-assisted partial nephrectomy (RAPN) increased. The rate of clampless
      NSS constantly increased over time. The use of at least one haemostatic agent has
      been significantly more adopted in the most recent surgical era (p < 0.001).
      CONCLUSIONS: The utilization rate of NSS in Italy is increasing, even in elective
      and more complex cases. RAPN has been progressively adopted, as well as the
      intraoperative utilization of haemostatic agents and the rate of clampless
      procedures.

PMID- 25583461
TI  - Biogenesis of cytosolic and nuclear iron-sulfur proteins and their role in genome
      stability.
AB  - Iron-sulfur (Fe-S) clusters are versatile protein cofactors that require numerous
      components for their synthesis and insertion into apoproteins. In eukaryotes,
      maturation of cytosolic and nuclear Fe-S proteins is accomplished by cooperation
      of the mitochondrial iron-sulfur cluster (ISC) assembly and export machineries,
      and the cytosolic iron-sulfur protein assembly (CIA) system. Currently, nine CIA
      proteins are known to specifically assist the two major steps of the biogenesis
      reaction. They are essential for cell viability and conserved from yeast to man.
      The essential character of this biosynthetic process is explained by the
      involvement of Fe-S proteins in central processes of life, e.g., protein
      translation and numerous steps of nuclear DNA metabolism such as DNA replication
      and repair. Malfunctioning of these latter Fe-S enzymes leads to genome
      instability, a hallmark of cancer. This review is focused on the maturation and
      biological function of cytosolic and nuclear Fe-S proteins, a topic of central
      interest for both basic and medical research. This article is part of a Special
      Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and
      diseases.

PMID- 25583462
TI  - The impact of high-risk cases on hospitals' risk-adjusted coronary artery bypass
      grafting mortality rankings.
AB  - BACKGROUND: Risk-adjusted mortality (RAM) models are increasingly used to
      evaluate hospital performance, but the validity of the RAM method has been
      questioned. Providers are concerned that these methods might not adequately
      account for the highest levels of risk and that treating high-risk cases will
      have a negative impact on RAM rankings. METHODS: Using cases of isolated coronary
      artery bypass grafting (CABG) performed at 1002 sites in the United States
      participating in The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery
      Database from 2008 to 2010 (N = 494,955), the STS CABG RAM model performance in
      high-risk patients was assessed. The ratios of observed to expected (O/E)
      perioperative mortality were compared among groups of hospitals with varying
      expected risks. Finally, RAM rates during the overall study period for each site
      were compared with its performance in a simulated "nightmare year" in which the
      site's highest risk cases over a 3-year period were concentrated into a 1-year
      period of exceptional risk. RESULTS: The average predicted mortality for center
      risk groups ranged from 1.46% for the lowest risk quintile to 2.87% for the
      highest. The O/E ratios for center risk quintiles 1 to 5 during the overall
      period were 1.01 (95% confidence interval, 0.96% to 1.06%), 1.00 (0.95% to
      1.04%), 0.98 (0.94% to 1.03%), 0.97 (0.93% to 1.01%), and 0.80 (0.77% to 0.84%),
      respectively. The sites' risk-adjusted mortality rates were not increased when
      the centers' highest risk cases were concentrated into a single "nightmare year."
      CONCLUSIONS: Our results show that the current risk-adjusted models accurately
      estimate CABG mortality and that hospitals accepting more high-risk CABG patients
      have equal or better outcomes than do those with predominately lower-risk
      patients.

PMID- 25583463
TI  - Midterm results of David V valve-sparing aortic root replacement in acute type A
      aortic dissection.
AB  - BACKGROUND: The David V valve-sparing aortic root replacement (David V) has been
      shown to provide excellent long-term valve function and low rates of valve
      related complications in the elective treatment of aortic root aneurysms. The
      safety and durability of the David V in the repair of acute type A aortic
      dissection (type A) are currently unclear. In this study, the midterm results of
      David V in the setting of type A aortic dissection were analyzed. METHODS: From
      2005 to 2013, 350 patients underwent surgical repair of type A aortic dissection.
      Outcomes were analyzed in 43 consecutive patients who received a David V during
      repair of type A aortic dissection. Patients were followed with annual
      postoperative echocardiograms. Follow-up was 85% complete, with a mean duration
      of 40 +/- 31 months. RESULTS: The mean age of these patients was 46 +/- 10 years.
      There were two operative deaths (4.7%), and 93% of patients required a hemiarch
      replacement (n = 32) or a total arch replacement (n = 8) using hypothermic
      circulatory arrest. Cusp repairs were performed in 6 (14%) patients; 51% of
      patients had 3+ or greater preoperative aortic insufficiency (AI), 83% of
      patients left the operating room with zero AI, and the remainder had 1+ AI or
      less. No patient in the follow-up period developed endocarditis or required
      aortic valve replacement. At midterm follow-up, freedom from 2+ AI was 94%, and
      freedom from aortic valve replacement was 100%. CONCLUSIONS: The David V can be
      performed with low morbidity and mortality in young patients presenting with type
      A aortic dissection who require aortic root replacement. At midterm follow-up,
      valve function is durable, and the incidence of valve-related complications is
      low.

PMID- 25583464
TI  - Contemporary bloodletting in cardiac surgical care.
AB  - BACKGROUND: Health care providers are seldom aware of the frequency and volume of
      phlebotomy for laboratory testing, bloodletting that often leads to hospital
      acquired anemia. Our objectives were to examine the frequency of laboratory
      testing in patients undergoing cardiac surgery, calculate cumulative phlebotomy
      volume from time of initial surgical consultation to hospital discharge, and
      propose strategies to reduce phlebotomy volume. METHODS: From January 1, 2012 to
      June 30, 2012, 1,894 patients underwent cardiac surgery at Cleveland Clinic;
      1,867 had 1 hospitalization and 27 had 2. Each laboratory test was associated
      with a test name and blood volume. Phlebotomy volume was estimated separately for
      the intensive care unit (ICU), hospital floors, and cumulatively. RESULTS: A
      total of 221,498 laboratory tests were performed, averaging 115 tests per
      patient. The most frequently performed tests were 88,068 blood gas analyses,
      39,535 coagulation tests, 30,421 complete blood counts, and 29,374 metabolic
      panels. Phlebotomy volume differed between ICU and hospital floors, with median
      volumes of 332 mL and 118 mL, respectively. Cumulative median volume for the
      entire hospital stay was 454 mL. More complex procedures were associated with
      higher overall phlebotomy volume than isolated procedures; eg, combined coronary
      artery bypass grafting (CABG) and valve procedure median volume was 653 mL
      (25th/75th percentiles, 428 of 1,065 mL) versus 448 mL (284 of 658 mL) for
      isolated CABG and 338 mL (237 of 619) for isolated valve procedures. CONCLUSIONS:
      We were astonished by the extent of bloodletting, with total phlebotomy volumes
      approaching amounts equivalent to 1 to 2 red blood cell units. Implementation of
      process improvement initiatives can potentially reduce phlebotomy volumes and
      resource utilization.

PMID- 25583465
TI  - Outcomes in aortic and mitral valve replacement with intervalvular fibrous body
      reconstruction.
AB  - BACKGROUND: Surgery for intervalvular fibrous body reconstruction in aortic and
      mitral valve replacement is a complex operation, although mandatory in some
      circumstances. The long-term result of this operation remains unknown. The
      objective of this study was to analyze the outcomes of this technique. METHODS: A
      descriptive and retrospective study was carried out to analyze operative
      morbidity and mortality in fibrous body reconstruction with the "David technique"
      and to evaluate the midterm and long-term results regarding durability and
      survival. RESULTS: A total of 40 consecutive patients underwent the David
      technique between 1997 and 2014. The mean age was 58 +/- 15 years and 62.5% were
      male. The indications were active endocarditis with paravalvular and fibrous body
      abscesses in 26 patients (group A) and massive calcification of the intervalvular
      fibrous body in 14 patients (group B). Mean European system for cardiac operative
      risk evaluation I predicted risk of mortality was 36 +/- 24 and 16 +/- 15,
      respectively. The hospital mortality rate was 15.3% in group A and 7.1% in group
      B. Survival rate after 1, 5, and 10 years was 65.4%, 57.7%, and 50% for group A
      and 92.9%, 85.7%, and 78.6% for group B. Freedom from reoperation at 1, 5, and 10
      years was 92.3%, 84.6%, and 76.9% for group A and 90.9%, 90.9%, and 90.9% for
      group B. Mean follow-up was 53 +/- 8 months. CONCLUSIONS: Although this complex
      operation is associated with high perioperative mortality, the long-term results
      are acceptable in patients where there are not suitable alternative procedures.

PMID- 25583466
TI  - Aortic valve replacement through right minithoracotomy: is it really biologically
      minimally invasive?
AB  - BACKGROUND: Minimally invasive aortic valve replacement through a right mini
      thoracotomy is a procedure developed in the past few years. Currently, the main
      limits of this technique are longer cardiopulmonary bypass time compared with the
      standard approach and the need for peripheral cannulation. METHODS: From January
      2010 to March 2014, 206 patients underwent an aortic valve replacement using a
      minimally invasive technique through a right mini-thoracotomy. Mean age was 71.4
      +/- 12.0 years, and 129 (62.6%) were male. In the first series of 42 patients,
      the vacuum-assisted venous drainage was obtained percutaneously through the
      groin. A totally central arterial and venous cannulation was adopted in the
      subsequent 164 patients. Two hundred patients (97.1%) received a bioprosthesis
      implanted with three 2-0 Prolene running sutures; a mechanical valve was
      implanted in six patients. One patient required reoperation. RESULTS: Aortic
      valve replacement was performed through a 4-6-cm skin incision at the third
      intercostal space. Overall cardiopulmonary bypass was 64.8 +/- 17.2 min, and
      aortic cross clamping was 51.8 +/- 14.9 min. In-hospital mortality was 1.5%
      (3/206). CONCLUSIONS: Our initial series confirms that aortic valve replacement
      performed through a right mini-thoracotomy is a safe procedure. When using
      running sutures, it is possible to obtain cardiopulmonary bypass and cross
      clamping times comparable to those for the standard approach. A central
      cannulation can be performed easily to avoid groin incisions. In conclusion, we
      believe that this kind of surgery could really be a biologically minimally
      invasive approach, rather than just an aesthetic choice.

PMID- 25583467
TI  - Very long-term outcomes of the Carpentier-Edwards Perimount valve in aortic
      position.
AB  - BACKGROUND: The Carpentier-Edwards Perimount pericardial bioprosthesis (Edwards
      Lifesciences, Irvine, CA) has demonstrated good long-term outcomes, but its
      durability remains unclear depending on age at implantation. We report our 20
      year experience with the Perimount valve implanted in the aortic position, with
      particular attention to the probability and time to reoperation required due to
      bioprosthesis deterioration. METHODS: From 1984 to 2008 at our center, 2,659
      patients (mean age, 70.7 +/- 10.4 years) underwent aortic valve replacement using
      the Perimount pericardial bioprostheses. Patients were prospectively followed on
      an annual basis (mean 6.7 +/- 4.8 years, range 0 to 24.6 years) with an
      echocardiogram at the time of follow-up. Cumulative follow-up was 18,404 valve
      years. Bioprosthesis structural valve deterioration was determined by strict
      echocardiographic assessment. RESULTS: Overall operative mortality was 2.8%.
      Actuarial survival rates including early deaths averaged 52.4% +/- 1.2%, 31.1% +/
      1.4%, and 14.4% +/- 1.7% after 10, 15, and 20 years of follow-up, respectively.
      Age-stratified freedom from reoperation due to structural valve deterioration at
      15 and 20 years was 70.8% +/- 4.1% and 38.1% +/- 5.6%, respectively, for the
      group aged 60 years or less, 82.7% +/- 2.9% and 59.6% +/- 7.6% for those 60 to 70
      years, and 98.1% +/- 0.8% at 15 years and above for the oldest group. Expected
      valve durability is 19.7 years for the entire cohort. CONCLUSIONS: With a low
      rate of valve-related events at 20 years, and particularly a low rate of
      structural valve deterioration, the Carpentier-Edwards Perimount pericardial
      bioprosthesis remains a reliable choice for a tissue valve in the aortic
      position, especially in patients over 60 years of age.

PMID- 25583468
TI  - Nonceliac gluten sensitivity.
AB  - During the past decade there has been an impressive increase in popularity of the
      gluten-free diet (GFD)-now the most trendy alimentary habit in the United States
      and other countries. According to recent surveys, as many as 100 million
      Americans will consume gluten-free products within a year. Operating under the
      concept that the GFD benefits only individuals with celiac disease, health care
      professionals have struggled to separate the wheat from the chaff; there are
      claims that eliminating gluten from the diet increases health and helps with
      weight loss, or even that gluten can be harmful to every human being. However,
      apart from unfounded trends, a disorder related to ingestion of gluten or gluten
      containing cereals, namely nonceliac gluten sensitivity (NCGS), has resurfaced in
      the literature, fueling a debate on the appropriateness of the GFD for people
      without celiac disease. Although there is clearly a fad component to the
      popularity of the GFD, there is also undisputable and increasing evidence for
      NCGS. However, we require a better understanding of the clinical presentation of
      NCGS, as well as its pathogenesis, epidemiology, management, and role in
      conditions such as irritable bowel syndrome, chronic fatigue, and autoimmunity.
      Before we can begin to identify and manage NCGS, there must be agreement on the
      nomenclature and definition of the disorder based on proper peer-reviewed
      scientific information. We review the most recent findings on NCGS and outline
      directions to dissipate some of the confusion related to this disorder. 

PMID- 25583469
TI  - Timely sleep facilitates declarative memory consolidation in infants.
AB  - Human infants devote the majority of their time to sleeping. However, very little
      is known about the role of sleep in early memory processing. Here we test 6- and
      12-mo-old infants' declarative memory for novel actions after a 4-h [Experiment
      (Exp.) 1] and 24-h delay (Exp. 2). Infants in a nap condition took an extended
      nap (>=30 min) within 4 h after learning, whereas infants in a no-nap condition
      did not. A comparison with age-matched control groups revealed that after both
      delays, only infants who had napped after learning remembered the target actions
      at the test. Additionally, after the 24-h delay, memory performance of infants in
      the nap condition was significantly higher than that of infants in the no-nap
      condition. This is the first experimental evidence to our knowledge for an
      enhancing role of sleep in the consolidation of declarative memories in the first
      year of life. 

PMID- 25583470
TI  - Geography and personality: why do different neighborhoods have different vibes?

PMID- 25583471
TI  - Isolation and determination of absolute configurations of insect-produced methyl
      branched hydrocarbons.
AB  - Although the effects of stereochemistry have been studied extensively for
      volatile insect pheromones, little is known about the effects of chirality in the
      nonvolatile methyl-branched hydrocarbons (MBCHs) used by many insects as contact
      pheromones. MBCHs generally contain one or more chiral centers and so two or more
      stereoisomeric forms are possible for each structure. However, it is not known
      whether insects biosynthesize these molecules in high stereoisomeric purity, nor
      is it known whether insects can distinguish the different stereoisomeric forms of
      MBCHs. This knowledge gap is due in part to the lack of methods for isolating
      individual MBCHs from the complex cuticular hydrocarbon (CHC) blends of insects,
      as well as the difficulty in determining the absolute configurations of the
      isolated MBCHs. To address these deficiencies, we report a straightforward method
      for the isolation of individual cuticular hydrocarbons from the complex CHC
      blend. The method was used to isolate 36 pure MBCHs from 20 species in nine
      insect orders. The absolute stereochemistries of the purified MBCHs then were
      determined by digital polarimetry. The absolute configurations of all of the
      isolated MBCHs were determined to be (R) by comparison with a library of
      synthesized, enantiomerically pure standards, suggesting that the biosynthetic
      pathways used to construct MBCHs are highly conserved within the Insecta. The
      development of a straightforward method for isolation of specific CHCs will
      enable determination of their functional roles by providing pure compounds for
      bioassays. 

PMID- 25583474
TI  - Aggressive mimicry coexists with mutualism in an aphid.
AB  - Understanding the evolutionary transition from interspecific exploitation to
      cooperation is a major challenge in evolutionary biology. Ant-aphid relationships
      represent an ideal system to this end because they encompass a coevolutionary
      continuum of interactions ranging from mutualism to antagonism. In this study, we
      report an unprecedented interaction along this continuum: aggressive mimicry in
      aphids. We show that two morphs clonally produced by the aphid Paracletus
      cimiciformis during its root-dwelling phase establish relationships with ants at
      opposite sides of the mutualism-antagonism continuum. Although one of these
      morphs exhibits the conventional trophobiotic (mutualistic) relationship with
      ants of the genus Tetramorium, aphids of the alternative morph are transported by
      the ants to their brood chamber and cared for as if they were true ant larvae.
      Gas chromatography-mass spectrometry analyses reveal that the innate cuticular
      hydrocarbon profile of the mimic morph resembles the profile of ant larvae more
      than that of the alternative, genetically identical nonmimic morph. Furthermore,
      we show that, once in the brood chamber, mimic aphids suck on ant larva
      hemolymph. These results not only add aphids to the limited list of arthropods
      known to biosynthesize the cuticular chemicals of their deceived hosts to exploit
      their resources but describe a remarkable case of plastic aggressive mimicry. The
      present work adds a previously unidentified dimension to the classical textbook
      paradigm of aphid-ant relationships by showcasing a complex system at the
      evolutionary interface between cooperation and exploitation. 

PMID- 25583472
TI  - Haptoglobin phenotype predicts the development of focal and global cerebral
      vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage.
AB  - Cerebral vasospasm (CV) and the resulting delayed cerebral ischemia (DCI)
      significantly contribute to poor outcomes following aneurysmal subarachnoid
      hemorrhage (aSAH). Free hemoglobin (Hb) within the subarachnoid space has been
      implicated in the pathogenesis of CV. Haptoglobin (Hp) binds free pro-oxidant Hb,
      thereby modulating its harmful effects. Humans can be of three Hp phenotypes: Hp1
      1, Hp2-1, or Hp2-2. In several disease states, the Hp2-2 protein has been
      associated with reduced ability to protect against toxic free Hb. We hypothesized
      that individuals with the Hp2-2 phenotype would have more CV, DCI, mortality, and
      worse functional outcomes after aSAH. In a sample of 74 aSAH patients, Hp2-2
      phenotype was significantly associated with increased focal moderate (P = 0.014)
      and severe (P = 0.008) CV and more global CV (P = 0.014) after controlling for
      covariates. Strong trends toward increased mortality (P = 0.079) and worse
      functional outcomes were seen for the Hp2-2 patients with modified Rankin scale
      at 6 wk (P = 0.076) and at 1 y (P = 0.051) and with Glasgow Outcome Scale
      Extended at discharge (P = 0.091) and at 1 y (P = 0.055). In conclusion, Hp2-2
      phenotype is an independent risk factor for the development of both focal and
      global CV and also predicts poor functional outcomes and mortality after aSAH. Hp
      phenotyping may serve as a clinically useful tool in the critical care management
      of aSAH patients by allowing for early prediction of those patients who require
      increased vigilance due to their inherent genetic risk for the development of CV
      and resulting DCI and poor outcomes. 

PMID- 25583475
TI  - Aldehydes and sugars from evolved precometary ice analogs: importance of ices in
      astrochemical and prebiotic evolution.
AB  - Evolved interstellar ices observed in dense protostellar molecular clouds may
      arguably be considered as part of precometary materials that will later fall on
      primitive telluric planets, bringing a wealth of complex organic compounds. In
      our laboratory, experiments reproducing the photo/thermochemical evolution of
      these ices are routinely performed. Following previous amino acid identifications
      in the resulting room temperature organic residues, we have searched for a
      different family of molecules of potential prebiotic interest. Using
      multidimensional gas chromatography coupled to time-of-flight mass spectrometry,
      we have detected 10 aldehydes, including the sugar-related glycolaldehyde and
      glyceraldehyde--two species considered as key prebiotic intermediates in the
      first steps toward the synthesis of ribonucleotides in a planetary environment.
      The presence of ammonia in water and methanol ice mixtures appears essential for
      the recovery of these aldehydes in the refractory organic residue at room
      temperature, although these products are free of nitrogen. We finally point out
      the importance of detecting aldehydes and sugars in extraterrestrial
      environments, in the gas phase of hot molecular clouds, and, more importantly, in
      comets and in primitive meteorites that have most probably seeded the Earth with
      organic material as early as 4.2 billion years ago.

PMID- 25583473
TI  - The butterfly effect in cancer: a single base mutation can remodel the cell.
AB  - We have compared the proteome, transcriptome, and metabolome of two cell lines:
      the human breast epithelial line MCF-10A and its mutant descendant MCF-10A
      H1047R. These cell lines are derived from the same parental stock and differ by a
      single amino acid substitution (H1047R) caused by a single nucleotide change in
      one allele of the PIK3CA gene, which encodes the catalytic subunit p110alpha of
      PI3K (phosphatidylinositol 3-kinase). They are considered isogenic. The H1047R
      mutation of PIK3CA is one of the most frequently encountered somatic cancer
      specific mutations. In MCF-10A, this mutation induces an extensive cellular
      reorganization that far exceeds the known signaling activities of PI3K. The
      changes are highly diverse, with examples in structural protein levels, the DNA
      repair machinery, and sterol synthesis. Gene set enrichment analysis reveals a
      highly significant concordance of the genes differentially expressed in MCF-10A
      H1047R cells and the established protein and RNA signatures of basal breast
      cancer. No such concordance was found with the specific gene signatures of other
      histological types of breast cancer. Our data document the power of a single base
      mutation, inducing an extensive remodeling of the cell toward the phenotype of a
      specific cancer. 

PMID- 25583477
TI  - Efficient meltwater drainage through supraglacial streams and rivers on the
      southwest Greenland ice sheet.
AB  - Thermally incised meltwater channels that flow each summer across melt-prone
      surfaces of the Greenland ice sheet have received little direct study. We use
      high-resolution WorldView-1/2 satellite mapping and in situ measurements to
      characterize supraglacial water storage, drainage pattern, and discharge across
      6,812 km(2) of southwest Greenland in July 2012, after a record melt event.
      Efficient surface drainage was routed through 523 high-order stream/river channel
      networks, all of which terminated in moulins before reaching the ice edge. Low
      surface water storage (3.6 +/- 0.9 cm), negligible impoundment by supraglacial
      lakes or topographic depressions, and high discharge to moulins (2.54-2.81 cm?d(
      1)) indicate that the surface drainage system conveyed its own storage volume
      every <2 d to the bed. Moulin discharges mapped inside ~52% of the source ice
      watershed for Isortoq, a major proglacial river, totaled ~41-98% of observed
      proglacial discharge, highlighting the importance of supraglacial river drainage
      to true outflow from the ice edge. However, Isortoq discharges tended lower than
      runoff simulations from the Modele Atmospherique Regional (MAR) regional climate
      model (0.056-0.112 km(3)?d(-1) vs. ~0.103 km(3)?d(-1)), and when integrated over
      the melt season, totaled just 37-75% of MAR, suggesting nontrivial subglacial
      water storage even in this melt-prone region of the ice sheet. We conclude that
      (i) the interior surface of the ice sheet can be efficiently drained under
      optimal conditions, (ii) that digital elevation models alone cannot fully
      describe supraglacial drainage and its connection to subglacial systems, and
      (iii) that predicting outflow from climate models alone, without recognition of
      subglacial processes, may overestimate true meltwater export from the ice sheet
      to the ocean. 

PMID- 25583476
TI  - Mutational landscape of gastric adenocarcinoma in Chinese: implications for
      prognosis and therapy.
AB  - Gastric cancer (GC) is a highly heterogeneous disease. To identify potential
      clinically actionable therapeutic targets that may inform individualized
      treatment strategies, we performed whole-exome sequencing on 78 GCs of differing
      histologies and anatomic locations, as well as whole-genome sequencing on two GC
      cases, each with three primary tumors and two matching lymph node metastases. The
      data showed two distinct GC subtypes with either high-clonality (HiC) or low
      clonality (LoC). The HiC subtype of intratumoral heterogeneity was associated
      with older age, TP53 (tumor protein P53) mutation, enriched C > G transition, and
      significantly shorter survival, whereas the LoC subtype was associated with
      younger age, ARID1A (AT rich interactive domain 1A) mutation, and significantly
      longer survival. Phylogenetic tree analysis of whole-genome sequencing data from
      multiple samples of two patients supported the clonal evolution of GC metastasis
      and revealed the accumulation of genetic defects that necessitate combination
      therapeutics. The most recurrently mutated genes, which were validated in a
      separate cohort of 216 cases by targeted sequencing, were members of the
      homologous recombination DNA repair, Wnt, and PI3K-ERBB pathways. Notably, the
      drugable NRG1 (neuregulin-1) and ERBB4 (V-Erb-B2 avian erythroblastic leukemia
      viral oncogene homolog 4) ligand-receptor pair were mutated in 10% of GC cases.
      Mutations of the BRCA2 (breast cancer 2, early onset) gene, found in 8% of our
      cohort and validated in The Cancer Genome Atlas GC cohort, were associated with
      significantly longer survivals. These data define distinct clinicogenetic forms
      of GC in the Chinese population that are characterized by specific mutation sets
      that can be investigated for efficacy of single and combination therapies. 

PMID- 25583478
TI  - Selective NFAT targeting in T cells ameliorates GvHD while maintaining antitumor
      activity.
AB  - Graft-versus-host disease (GvHD) is a life-threatening immunological complication
      after allogenic hematopoietic stem cell transplantation (allo-HCT). The intrinsic
      graft-versus-leukemia (GvL) effect, however, is the desirable curative benefit.
      Patients with acute GvHD are treated with cyclosporine A (CsA) or tacrolimus
      (FK506), which not only often causes severe adverse effects, but also interferes
      with the anticipated GvL. Both drugs inhibit calcineurin, thus at first
      suppressing activation of the nuclear factor of activated T cells (NFAT).
      Therefore, we explored the specific contribution of individual NFAT factors in
      donor T cells in animal models of GvHD and GvL. Ablation of NFAT1, NFAT2, or a
      combination of both resulted in ameliorated GvHD, due to reduced proliferation,
      target tissue homing, and impaired effector function of allogenic donor T cells.
      In contrast, the frequency of Foxp3(+) regulatory T (Treg) cells was increased
      and NFAT-deficient Tregs were fully protective in GvHD. CD8(+) T-cell recall
      response and, importantly, the beneficial antitumor activity were largely
      preserved in NFAT-deficient effector T cells. Thus, specific inhibition of NFAT
      opens an avenue for an advanced therapy of GvHD maintaining protective GvL. 

PMID- 25583479
TI  - Mutant glucocerebrosidase in Gaucher disease recruits Hsp27 to the Hsp90
      chaperone complex for proteasomal degradation.
AB  - Gaucher disease is caused by mutations of the GBA1 gene, which encodes the
      lysosomal anchored gluococerebrosidase (GCase). GBA1 mutations commonly result in
      protein misfolding, abnormal chaperone recognition, and premature degradation,
      but are less likely to affect catalytic activity. In the present study, we
      demonstrate that the Hsp90/HOP/Cdc37 complex recruits Hsp27 after recognition of
      GCase mutants with subsequent targeting of GCase mutant peptides to degradation
      mechanisms such as VCP and the 26S proteasome. Inhibition of Hsp27 not only
      increased the quantity of enzyme but also enhanced GCase activity in fibroblasts
      derived from patients with Gaucher disease. These findings provide insight into a
      possible therapeutic strategy for protein misfolding diseases by correcting
      chaperone binding and altering subsequent downstream patterns of protein
      degradation. 

PMID- 25583480
TI  - Geographically varying associations between personality and life satisfaction in
      the London metropolitan area.
AB  - Residential location is thought to influence people's well-being, but different
      individuals may value residential areas differently. We examined how life
      satisfaction and personality traits are geographically distributed within the UK
      London metropolitan area, and how the strength of associations between
      personality traits and life satisfaction vary by residential location (i.e.,
      personality-neighborhood interactions). Residential area was recorded at the
      level of postal districts (216 districts, n = 56,019 participants). Results
      indicated that the strength of associations between personality traits and life
      satisfaction depended on neighborhood characteristics. Higher openness to
      experience was more positively associated with life satisfaction in postal
      districts characterized by higher average openness to experience, population
      density, and ethnic diversity. Higher agreeableness and conscientiousness were
      more strongly associated with life satisfaction in postal districts with lower
      overall levels of life satisfaction. The associations of extraversion and
      emotional stability were not modified by neighborhood characteristics. These
      findings suggest that people's life satisfaction depends, in part, on the
      interaction between individual personality and particular features of the places
      they live. 

PMID- 25583481
TI  - Inhibition of oxidative metabolism leads to p53 genetic inactivation and
      transformation in neural stem cells.
AB  - Alterations of mitochondrial metabolism and genomic instability have been
      implicated in tumorigenesis in multiple tissues. High-grade glioma (HGG), one of
      the most lethal human neoplasms, displays genetic modifications of Krebs cycle
      components as well as electron transport chain (ETC) alterations. Furthermore,
      the p53 tumor suppressor, which has emerged as a key regulator of mitochondrial
      respiration at the expense of glycolysis, is genetically inactivated in a large
      proportion of HGG cases. Therefore, it is becoming evident that genetic
      modifications can affect cell metabolism in HGG; however, it is currently unclear
      whether mitochondrial metabolism alterations could vice versa promote genomic
      instability as a mechanism for neoplastic transformation. Here, we show that, in
      neural progenitor/stem cells (NPCs), which can act as HGG cell of origin,
      inhibition of mitochondrial metabolism leads to p53 genetic inactivation.
      Impairment of respiration via inhibition of complex I or decreased mitochondrial
      DNA copy number leads to p53 genetic loss and a glycolytic switch. p53 genetic
      inactivation in ETC-impaired neural stem cells is caused by increased reactive
      oxygen species and associated oxidative DNA damage. ETC-impaired cells display a
      marked growth advantage in the presence or absence of oncogenic RAS, and form
      undifferentiated tumors when transplanted into the mouse brain. Finally, p53
      mutations correlated with alterations in ETC subunit composition and activity in
      primary glioma-initiating neural stem cells. Together, these findings provide
      previously unidentified insights into the relationship between mitochondria,
      genomic stability, and tumor suppressive control, with implications for our
      understanding of brain cancer pathogenesis. 

PMID- 25583484
TI  - Benthic perspective on Earth's oldest evidence for oxygenic photosynthesis.
AB  - The Great Oxidation Event (GOE) is currently viewed as a protracted process
      during which atmospheric oxygen increased above ~10(-5) times the present
      atmospheric level (PAL). This threshold represents an estimated upper limit for
      sulfur isotope mass-independent fractionation (S-MIF), an Archean signature of
      atmospheric anoxia that begins to disappear from the rock record at 2.45 Ga.
      However, an increasing number of papers have suggested that the timing for
      oxidative continental weathering, and by conventional thinking the onset of
      atmospheric oxygenation, was hundreds of million years earlier than previously
      thought despite the presence of S-MIF. We suggest that this apparent discrepancy
      can be resolved by the earliest oxidative-weathering reactions occurring in
      benthic and soil environments at profound redox disequilibrium with the
      atmosphere, such as biological soil crusts and freshwater microbial mats covering
      riverbed, lacustrine, and estuarine sediments. We calculate that oxygenic
      photosynthesis in these millimeter-thick ecosystems provides sufficient oxidizing
      equivalents to mobilize sulfate and redox-sensitive trace metals from land to the
      oceans while the atmosphere itself remained anoxic with its attendant S-MIF
      signature. As continental freeboard increased significantly between 3.0 and 2.5
      Ga, the chemical and isotopic signatures of benthic oxidative weathering would
      have become more globally significant from a mass-balance perspective. These
      observations help reconcile evidence for pre-GOE oxidative weathering with the
      history of atmospheric chemistry, and support the plausible antiquity of a
      terrestrial biosphere populated by cyanobacteria well before the GOE. 

PMID- 25583482
TI  - Concerted copy number variation balances ribosomal DNA dosage in human and mouse
      genomes.
AB  - Tandemly repeated ribosomal DNA (rDNA) arrays are among the most evolutionary
      dynamic loci of eukaryotic genomes. The loci code for essential cellular
      components, yet exhibit extensive copy number (CN) variation within and between
      species. CN might be partly determined by the requirement of dosage balance
      between the 5S and 45S rDNA arrays. The arrays are nonhomologous, physically
      unlinked in mammals, and encode functionally interdependent RNA components of the
      ribosome. Here we show that the 5S and 45S rDNA arrays exhibit concerted CN
      variation (cCNV). Despite 5S and 45S rDNA elements residing on different
      chromosomes and lacking sequence similarity, cCNV between these loci is strong,
      evolutionarily conserved in humans and mice, and manifested across individual
      genotypes in natural populations and pedigrees. Finally, we observe that
      bisphenol A induces rapid and parallel modulation of 5S and 45S rDNA CN. Our
      observations reveal a novel mode of genome variation, indicate that natural
      selection contributed to the evolution and conservation of cCNV, and support the
      hypothesis that 5S CN is partly determined by the requirement of dosage balance
      with the 45S rDNA array. We suggest that human disease variation might be traced
      to disrupted rDNA dosage balance in the genome. 

PMID- 25583483
TI  - STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson's
      disease.
AB  - Parkinson's disease (PD) is characterized by the degeneration of dopaminergic
      neurons in the substantia nigra pars compacta (SNc). The loss of SNc dopaminergic
      neurons affects the plasticity of striatal neurons and leads to significant motor
      and cognitive disabilities during the progression of the disease. PARK2 encodes
      for the E3 ubiquitin ligase parkin and is implicated in genetic and sporadic PD.
      Mutations in PARK2 are a major contributing factor in the early onset of
      autosomal-recessive juvenile parkinsonism (AR-JP), although the mechanisms by
      which a disruption in parkin function contributes to the pathophysiology of PD
      remain unclear. Here we demonstrate that parkin is an E3 ligase for STEP61
      (striatal-enriched protein tyrosine phosphatase), a protein tyrosine phosphatase
      implicated in several neuropsychiatric disorders. In cellular models, parkin
      ubiquitinates STEP61 and thereby regulates its level through the proteasome
      system, whereas clinically relevant parkin mutants fail to do so. STEP61 protein
      levels are elevated on acute down-regulation of parkin or in PARK2 KO rat
      striatum. Relevant to PD, STEP61 accumulates in the striatum of human sporadic PD
      and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice. The
      increase in STEP61 is associated with a decrease in the phosphorylation of its
      substrate ERK1/2 and the downstream target of ERK1/2, pCREB [phospho-CREB (cAMP
      response element-binding protein)]. These results indicate that STEP61 is a novel
      substrate of parkin, although further studies are necessary to determine whether
      elevated STEP61 levels directly contribute to the pathophysiology of PD. 

PMID- 25583485
TI  - Relative contribution of TARPs gamma-2 and gamma-7 to cerebellar excitatory
      synaptic transmission and motor behavior.
AB  - Transmembrane AMPA receptor regulatory proteins (TARPs) play an essential role in
      excitatory synaptic transmission throughout the central nervous system (CNS) and
      exhibit subtype-specific effects on AMPA receptor (AMPAR) trafficking, gating,
      and pharmacology. The function of TARPs has largely been determined through work
      on canonical type I TARPs such as stargazin (TARP gamma-2), absent in the ataxic
      stargazer mouse. Little is known about the function of atypical type II TARPs,
      such as TARP gamma-7, which exhibits variable effects on AMPAR function. Because
      gamma-2 and gamma-7 are both strongly expressed in multiple cell types in the
      cerebellum, we examined the relative contribution of gamma-2 and gamma-7 to both
      synaptic transmission in the cerebellum and motor behavior by using both the
      stargazer mouse and a gamma-7 knockout (KO) mouse. We found that the loss of
      gamma-7 alone had little effect on climbing fiber (cf) responses in Purkinje
      neurons (PCs), yet the additional loss of gamma-2 all but abolished cf responses.
      In contrast, gamma-7 failed to make a significant contribution to excitatory
      transmission in stellate cells and granule cells. In addition, we generated a PC
      specific deletion of gamma-2, with and without gamma-7 KO background, to examine
      the relative contribution of gamma-2 and gamma-7 to PC-dependent motor behavior.
      Selective deletion of gamma-2 in PCs had little effect on motor behavior, yet the
      additional loss of gamma-7 resulted in a severe disruption in motor behavior.
      Thus, gamma-7 is capable of supporting a component of excitatory transmission in
      PCs, sufficient to maintain essentially normal motor behavior, in the absence of
      gamma-2. 

PMID- 25583487
TI  - Dark-matter QCD-axion searches.
AB  - In the late 20th century, cosmology became a precision science. Now, at the
      beginning of the next century, the parameters describing how our universe evolved
      from the Big Bang are generally known to a few percent. One key parameter is the
      total mass density of the universe. Normal matter constitutes only a small
      fraction of the total mass density. Observations suggest this additional mass,
      the dark matter, is cold (that is, moving nonrelativistically in the early
      universe) and interacts feebly if at all with normal matter and radiation.
      There's no known such elementary particle, so the strong presumption is the dark
      matter consists of particle relics of a new kind left over from the Big Bang. One
      of the most important questions in science is the nature of this dark matter. One
      attractive particle dark-matter candidate is the axion. The axion is a
      hypothetical elementary particle arising in a simple and elegant extension to the
      standard model of particle physics that nulls otherwise observable CP-violating
      effects (where CP is the product of charge reversal C and parity inversion P) in
      quantum chromo dynamics (QCD). A light axion of mass 10(-(6-3)) eV (the invisible
      axion) would couple extraordinarily weakly to normal matter and radiation and
      would therefore be extremely difficult to detect in the laboratory. However, such
      an axion is a compelling dark-matter candidate and is therefore a target of a
      number of searches. Compared with other particle dark-matter candidates, the
      plausible range of axion dark-matter couplings and masses is narrowly
      constrained. This focused search range allows for definitive searches, where a
      nonobservation would seriously impugn the dark-matter QCD-axion hypothesis. Axion
      searches use a wide range of technologies, and the experiment sensitivities are
      now reaching likely dark-matter axion couplings and masses. This article is a
      selective overview of the current generation of sensitive axion searches. Not all
      techniques and experiments are discussed, but I hope to give a sense of the
      current experimental landscape of the search for dark-matter axions. 

PMID- 25583486
TI  - Central role for the insular cortex in mediating conditioned responses to
      anticipatory cues.
AB  - Reward-related circuits are fundamental for initiating feeding on the basis of
      food-predicting cues, whereas gustatory circuits are believed to be involved in
      the evaluation of food during consumption. However, accumulating evidence
      challenges such a rigid separation. The insular cortex (IC), an area largely
      studied in rodents for its role in taste processing, is involved in representing
      anticipatory cues. Although IC responses to anticipatory cues are well
      established, the role of IC cue-related activity in mediating feeding behaviors
      is poorly understood. Here, we examined the involvement of the IC in the
      expression of cue-triggered food approach in mice trained with a Pavlovian
      conditioning paradigm. We observed a significant change in neuronal firing during
      presentation of the cue. Pharmacological silencing of the IC inhibited food port
      approach. Such a behavior could be recapitulated by temporally selective
      inactivation during the cue. These findings represent the first evidence, to our
      knowledge, that cue-evoked neuronal activity in the mouse IC modulates behavioral
      output, and demonstrate a causal link between cue responses and feeding
      behaviors. 

PMID- 25583488
TI  - Metal-free organic sensitizers for use in water-splitting dye-sensitized
      photoelectrochemical cells.
AB  - Solar fuel generation requires the efficient capture and conversion of visible
      light. In both natural and artificial systems, molecular sensitizers can be tuned
      to capture, convert, and transfer visible light energy. We demonstrate that a
      series of metal-free porphyrins can drive photoelectrochemical water splitting
      under broadband and red light (lambda > 590 nm) illumination in a dye-sensitized
      TiO2 solar cell. We report the synthesis, spectral, and electrochemical
      properties of the sensitizers. Despite slow recombination of photoinjected
      electrons with oxidized porphyrins, photocurrents are low because of low
      injection yields and slow electron self-exchange between oxidized porphyrins. The
      free-base porphyrins are stable under conditions of water photoelectrolysis and
      in some cases photovoltages in excess of 1 V are observed. 

PMID- 25583489
TI  - Natural variations of copper and sulfur stable isotopes in blood of
      hepatocellular carcinoma patients.
AB  - The widespread hypoxic conditions of the tumor microenvironment can impair the
      metabolism of bioessential elements such as copper and sulfur, notably by
      changing their redox state and, as a consequence, their ability to bind specific
      molecules. Because competing redox state is known to drive isotopic
      fractionation, we have used here the stable isotope compositions of copper
      ((65)Cu/(63)Cu) and sulfur ((34)S/(32)S) in the blood of patients with
      hepatocellular carcinoma (HCC) as a tool to explore the cancer-driven copper and
      sulfur imbalances. We report that copper is (63)Cu-enriched by ~0.40/00 and
      sulfur is (32)S-enriched by ~1.50/00 in the blood of patients compared with that
      of control subjects. As expected, HCC patients have more copper in red blood
      cells and serum compared with control subjects. However, the isotopic signature
      of this blood extra copper burden is not in favor of a dietary origin but rather
      suggests a reallocation in the body of copper bound to cysteine-rich proteins
      such as metallothioneins. The magnitude of the sulfur isotope effect is similar
      in red blood cells and serum of HCC patients, implying that sulfur fractionation
      is systemic. The (32)S-enrichment of sulfur in the blood of HCC patients is
      compatible with the notion that sulfur partly originates from tumor-derived
      sulfides. The measurement of natural variations of stable isotope compositions,
      using techniques developed in the field of Earth sciences, can provide new means
      to detect and quantify cancer metabolic changes and provide insights into
      underlying mechanisms. 

PMID- 25583490
TI  - Metabotropic glutamate receptor 3 activation is required for long-term depression
      in medial prefrontal cortex and fear extinction.
AB  - Clinical studies have revealed that genetic variations in metabotropic glutamate
      receptor 3 (mGlu3) affect performance on cognitive tasks dependent upon the
      prefrontal cortex (PFC) and may be linked to psychiatric conditions such as
      schizophrenia, bipolar disorder, and addiction. We have performed a series of
      studies aimed at understanding how mGlu3 influences PFC function and cognitive
      behaviors. In the present study, we found that activation of mGlu3 can induce
      long-term depression in the mouse medial PFC (mPFC) in vitro. Furthermore, in
      vivo administration of a selective mGlu3 negative allosteric modulator impaired
      learning in the mPFC-dependent fear extinction task. The results of these studies
      implicate mGlu3 as a major regulator of PFC function and cognition. Additionally,
      potentiators of mGlu3 may be useful in alleviating prefrontal impairments
      associated with several CNS disorders. 

PMID- 25583491
TI  - Altered ubiquitin causes perturbed calcium homeostasis, hyperactivation of
      calpain, dysregulated differentiation, and cataract.
AB  - Although the ocular lens shares many features with other tissues, it is unique in
      that it retains its cells throughout life, making it ideal for studies of
      differentiation/development. Precipitation of proteins results in lens
      opacification, or cataract, the major blinding disease. Lysines on ubiquitin (Ub)
      determine fates of Ub-protein substrates. Information regarding ubiquitin
      proteasome systems (UPSs), specifically of K6 in ubiquitin, is undeveloped. We
      expressed in the lens a mutant Ub containing a K6W substitution (K6W-Ub). Protein
      profiles of lenses that express wild-type ubiquitin (WT-Ub) or K6W-Ub differ by
      only ~2%. Despite these quantitatively minor differences, in K6W-Ub lenses and
      multiple model systems we observed a fourfold Ca(2+) elevation and
      hyperactivation of calpain in the core of the lens, as well as calpain-associated
      fragmentation of critical lens proteins including Filensin, Fodrin, Vimentin,
      beta-Crystallin, Caprin family member 2, and tudor domain containing 7.
      Truncations can be cataractogenic. Additionally, we observed accumulation of gap
      junction Connexin43, and diminished Connexin46 levels in vivo and in vitro. These
      findings suggest that mutation of Ub K6 alters UPS function, perturbs gap
      junction function, resulting in Ca(2+) elevation, hyperactivation of calpain, and
      associated cleavage of substrates, culminating in developmental defects and a
      cataractous lens. The data show previously unidentified connections between UPS
      and calpain-based degradative systems and advance our understanding of roles for
      Ub K6 in eye development. They also inform about new approaches to delay cataract
      and other protein precipitation diseases. 

PMID- 25583492
TI  - Autophagy-independent functions of UVRAG are essential for peripheral naive T
      cell homeostasis.
AB  - UV radiation resistance-associated gene (UVRAG) encodes a tumor suppressor with
      putative roles in autophagy, endocytic trafficking, and DNA damage repair but its
      in vivo role in T cells is unknown. Because conditional homozygous deletion of
      Uvrag in mice results in early embryonic lethality, we generated T-cell-specific
      UVRAG-deficient mice that lacked UVRAG expression specifically in T cells. This
      loss of UVRAG led to defects in peripheral homeostasis that could not be
      explained by the increased sensitivity to cell death and impaired proliferation
      observed for other autophagy-related gene knockout mice. Instead, UVRAG-deficient
      T-cells exhibited normal mitochondrial clearance and activation-induced
      autophagy, suggesting that UVRAG has an autophagy-independent role that is
      critical for peripheral naive T-cell homeostatic proliferation. In vivo, T-cell
      specific loss of UVRAG dampened CD8(+) T-cell responses to LCMV infection in
      mice, delayed viral clearance, and impaired memory T-cell generation. Our data
      provide novel insights into the control of autophagy in T cells and identify
      UVRAG as a new regulator of naive peripheral T-cell homeostasis. 

PMID- 25583494
TI  - Nonprice incentives and energy conservation.
AB  - In the electricity sector, energy conservation through technological and
      behavioral change is estimated to have a savings potential of 123 million metric
      tons of carbon per year, which represents 20% of US household direct emissions in
      the United States. In this article, we investigate the effectiveness of nonprice
      information strategies to motivate conservation behavior. We introduce
      environment and health-based messaging as a behavioral strategy to reduce energy
      use in the home and promote energy conservation. In a randomized controlled trial
      with real-time appliance-level energy metering, we find that environment and
      health-based information strategies, which communicate the environmental and
      public health externalities of electricity production, such as pounds of
      pollutants, childhood asthma, and cancer, outperform monetary savings information
      to drive behavioral change in the home. Environment and health-based information
      treatments motivated 8% energy savings versus control and were particularly
      effective on families with children, who achieved up to 19% energy savings. Our
      results are based on a panel of 3.4 million hourly appliance-level kilowatt-hour
      observations for 118 residences over 8 mo. We discuss the relative impacts of
      both cost-savings information and environmental health messaging strategies with
      residential consumers. 

PMID- 25583493
TI  - Novel recurrently mutated genes in African American colon cancers.
AB  - We used whole-exome and targeted sequencing to characterize somatic mutations in
      103 colorectal cancers (CRC) from African Americans, identifying 20 new genes as
      significantly mutated in CRC. Resequencing 129 Caucasian derived CRCs confirmed a
      15-gene set as a preferential target for mutations in African American CRCs. Two
      predominant genes, ephrin type A receptor 6 (EPHA6) and folliculin (FLCN), with
      mutations exclusive to African American CRCs, are by genetic and biological
      criteria highly likely African American CRC driver genes. These previously
      unsuspected differences in the mutational landscapes of CRCs arising among
      individuals of different ethnicities have potential to impact on broader
      disparities in cancer behaviors. 

PMID- 25583495
TI  - Strength and duration of perisomatic GABAergic inhibition depend on distance
      between synaptically connected cells.
AB  - GABAergic perisoma-inhibiting fast-spiking interneurons (PIIs) effectively
      control the activity of large neuron populations by their wide axonal
      arborizations. It is generally assumed that the output of one PII to its target
      cells is strong and rapid. Here, we show that, unexpectedly, both strength and
      time course of PII-mediated perisomatic inhibition change with distance between
      synaptically connected partners in the rodent hippocampus. Synaptic signals
      become weaker due to lower contact numbers and decay more slowly with distance,
      very likely resulting from changes in GABAA receptor subunit composition. When
      distance-dependent synaptic inhibition is introduced to a rhythmically active
      neuronal network model, randomly driven principal cell assemblies are strongly
      synchronized by the PIIs, leading to higher precision in principal cell spike
      times than in a network with uniform synaptic inhibition. 

PMID- 25583496
TI  - Translation initiation mediated by RNA looping.
AB  - Eukaryotic translation initiation commences at the initiation codon near the 5'
      end of mRNA by a 40S ribosomal subunit, and the recruitment of a 40S ribosome to
      an mRNA is facilitated by translation initiation factors interacting with the
      m(7)G cap and/or poly(A) tail. The 40S ribosome recruited to an mRNA is then
      transferred to the AUG initiation codon with the help of translation initiation
      factors. To understand the mechanism by which the ribosome finds an initiation
      codon, we investigated the role of eIF4G in finding the translational initiation
      codon. An artificial polypeptide eIF4G fused with MS2 was localized downstream of
      the reporter gene through MS2-binding sites inserted in the 3' UTR of the mRNA.
      Translation of the reporter was greatly enhanced by the eIF4G-MS2 fusion protein
      regardless of the presence of a cap structure. Moreover, eIF4G-MS2 tethered at
      the 3' UTR enhanced translation of the second cistron of a dicistronic mRNA. The
      encephalomyocarditis virus internal ribosome entry site, a natural translational
      enhancing element facilitating translation through an interaction with eIF4G,
      positioned downstream of a reporter gene, also enhanced translation of the
      upstream gene in a cap-independent manner. Finally, we mathematically modeled the
      effect of distance between the cap structure and initiation codon on the
      translation efficiency of mRNAs. The most plausible explanation for translational
      enhancement by the translational-enhancing sites is recognition of the initiation
      codon by the ribosome bound to the ribosome-recruiting sites through "RNA
      looping." The RNA looping hypothesis provides a logical explanation for
      augmentation of translation by enhancing elements located upstream and/or
      downstream of a protein-coding region. 

PMID- 25583497
TI  - T box riboswitches in Actinobacteria: translational regulation via novel tRNA
      interactions.
AB  - The T box riboswitch regulates many amino acid-related genes in Gram-positive
      bacteria. T box riboswitch-mediated gene regulation was shown previously to occur
      at the level of transcription attenuation via structural rearrangements in the 5'
      untranslated (leader) region of the mRNA in response to binding of a specific
      uncharged tRNA. In this study, a novel group of isoleucyl-tRNA synthetase gene
      (ileS) T box leader sequences found in organisms of the phylum Actinobacteria was
      investigated. The Stem I domains of these RNAs lack several highly conserved
      elements that are essential for interaction with the tRNA ligand in other T box
      RNAs. Many of these RNAs were predicted to regulate gene expression at the level
      of translation initiation through tRNA-dependent stabilization of a helix that
      sequesters a sequence complementary to the Shine-Dalgarno (SD) sequence, thus
      freeing the SD sequence for ribosome binding and translation initiation. We
      demonstrated specific binding to the cognate tRNA(Ile) and tRNA(Ile)-dependent
      structural rearrangements consistent with regulation at the level of translation
      initiation, providing the first biochemical demonstration, to our knowledge, of
      translational regulation in a T box riboswitch. 

PMID- 25583499
TI  - Forecasting the epicenter of a future major earthquake.

PMID- 25583498
TI  - Recent shifts in the occurrence, cause, and magnitude of animal mass mortality
      events.
AB  - Mass mortality events (MMEs) are rapidly occurring catastrophic demographic
      events that punctuate background mortality levels. Individual MMEs are staggering
      in their observed magnitude: removing more than 90% of a population, resulting in
      the death of more than a billion individuals, or producing 700 million tons of
      dead biomass in a single event. Despite extensive documentation of individual
      MMEs, we have no understanding of the major features characterizing the
      occurrence and magnitude of MMEs, their causes, or trends through time. Thus, no
      framework exists for contextualizing MMEs in the wake of ongoing global and
      regional perturbations to natural systems. Here we present an analysis of 727
      published MMEs from across the globe, affecting 2,407 animal populations. We show
      that the magnitude of MMEs has been intensifying for birds, fishes, and marine
      invertebrates; invariant for mammals; and decreasing for reptiles and amphibians.
      These shifts in magnitude proved robust when we accounted for an increase in the
      occurrence of MMEs since 1940. However, it remains unclear whether the increase
      in the occurrence of MMEs represents a true pattern or simply a perceived
      increase. Regardless, the increase in MMEs appears to be associated with a rise
      in disease emergence, biotoxicity, and events produced by multiple interacting
      stressors, yet temporal trends in MME causes varied among taxa and may be
      associated with increased detectability. In addition, MMEs with the largest
      magnitudes were those that resulted from multiple stressors, starvation, and
      disease. These results advance our understanding of rare demographic processes
      and their relationship to global and regional perturbations to natural systems. 

PMID- 25583500
TI  - New human-specific brain landmark: the depth asymmetry of superior temporal
      sulcus.
AB  - Identifying potentially unique features of the human cerebral cortex is a first
      step to understanding how evolution has shaped the brain in our species. By
      analyzing MR images obtained from 177 humans and 73 chimpanzees, we observed a
      human-specific asymmetry in the superior temporal sulcus at the heart of the
      communication regions and which we have named the "superior temporal asymmetrical
      pit" (STAP). This 45-mm-long segment ventral to Heschl's gyrus is deeper in the
      right hemisphere than in the left in 95% of typical human subjects, from
      infanthood till adulthood, and is present, irrespective of handedness, language
      lateralization, and sex although it is greater in males than in females. The STAP
      also is seen in several groups of atypical subjects including persons with situs
      inversus, autistic spectrum disorder, Turner syndrome, and corpus callosum
      agenesis. It is explained in part by the larger number of sulcal interruptions in
      the left than in the right hemisphere. Its early presence in the infants of this
      study as well as in fetuses and premature infants suggests a strong genetic
      influence. Because this asymmetry is barely visible in chimpanzees, we recommend
      the STAP region during midgestation as an important phenotype to investigate
      asymmetrical variations of gene expression among the primate lineage. This
      genetic target may provide important insights regarding the evolution of the
      crucial cognitive abilities sustained by this sulcus in our species, namely
      communication and social cognition. 

PMID- 25583501
TI  - Hierarchical sparse coding in the sensory system of Caenorhabditis elegans.
AB  - Animals with compact sensory systems face an encoding problem where a small
      number of sensory neurons are required to encode information about its
      surrounding complex environment. Using Caenorhabditis elegans worms as a model,
      we ask how chemical stimuli are encoded by a small and highly connected sensory
      system. We first generated a comprehensive library of transgenic worms where each
      animal expresses a genetically encoded calcium indicator in individual sensory
      neurons. This library includes the vast majority of the sensory system in C.
      elegans. Imaging from individual sensory neurons while subjecting the worms to
      various stimuli allowed us to compile a comprehensive functional map of the
      sensory system at single neuron resolution. The functional map reveals that
      despite the dense wiring, chemosensory neurons represent the environment using
      sparse codes. Moreover, although anatomically closely connected, chemo- and
      mechano-sensory neurons are functionally segregated. In addition, the code is
      hierarchical, where few neurons participate in encoding multiple cues, whereas
      other sensory neurons are stimulus specific. This encoding strategy may have
      evolved to mitigate the constraints of a compact sensory system. 

PMID- 25583502
TI  - Integrative analysis of sequencing and array genotype data for discovering
      disease associations with rare mutations.
AB  - In the large cohorts that have been used for genome-wide association studies
      (GWAS), it is prohibitively expensive to sequence all cohort members. A cost
      effective strategy is to sequence subjects with extreme values of quantitative
      traits or those with specific diseases. By imputing the sequencing data from the
      GWAS data for the cohort members who are not selected for sequencing, one can
      dramatically increase the number of subjects with information on rare variants.
      However, ignoring the uncertainties of imputed rare variants in downstream
      association analysis will inflate the type I error when sequenced subjects are
      not a random subset of the GWAS subjects. In this article, we provide a valid and
      efficient approach to combining observed and imputed data on rare variants. We
      consider commonly used gene-level association tests, all of which are constructed
      from the score statistic for assessing the effects of individual variants on the
      trait of interest. We show that the score statistic based on the observed
      genotypes for sequenced subjects and the imputed genotypes for nonsequenced
      subjects is unbiased. We derive a robust variance estimator that reflects the
      true variability of the score statistic regardless of the sampling scheme and
      imputation quality, such that the corresponding association tests always have
      correct type I error. We demonstrate through extensive simulation studies that
      the proposed tests are substantially more powerful than the use of accurately
      imputed variants only and the use of sequencing data alone. We provide an
      application to the Women's Health Initiative. The relevant software is freely
      available. 

PMID- 25583503
TI  - The draft genome of Tibetan hulless barley reveals adaptive patterns to the high
      stressful Tibetan Plateau.
AB  - The Tibetan hulless barley (Hordeum vulgare L. var. nudum), also called "Qingke"
      in Chinese and "Ne" in Tibetan, is the staple food for Tibetans and an important
      livestock feed in the Tibetan Plateau. The diploid nature and adaptation to
      diverse environments of the highland give it unique resources for genetic
      research and crop improvement. Here we produced a 3.89-Gb draft assembly of
      Tibetan hulless barley with 36,151 predicted protein-coding genes. Comparative
      analyses revealed the divergence times and synteny between barley and other
      representative Poaceae genomes. The expansion of the gene family related to
      stress responses was found in Tibetan hulless barley. Resequencing of 10 barley
      accessions uncovered high levels of genetic variation in Tibetan wild barley and
      genetic divergence between Tibetan and non-Tibetan barley genomes. Selective
      sweep analyses demonstrate adaptive correlations of genes under selection with
      extensive environmental variables. Our results not only construct a genomic
      framework for crop improvement but also provide evolutionary insights of highland
      adaptation of Tibetan hulless barley. 

PMID- 25583505
TI  - The effects of bilingualism on the white matter structure of the brain.
AB  - Recent studies suggest that learning and using a second language (L2) can affect
      brain structure, including the structure of white matter (WM) tracts. This
      observation comes from research looking at early and older bilingual individuals
      who have been using both their first and second languages on an everyday basis
      for many years. This study investigated whether young, highly immersed late
      bilinguals would also show structural effects in the WM that can be attributed to
      everyday L2 use, irrespective of critical periods or the length of L2 learning.
      Our Tract-Based Spatial Statistics analysis revealed higher fractional anisotropy
      values for bilinguals vs. monolinguals in several WM tracts that have been linked
      to language processing and in a pattern closely resembling the results reported
      for older and early bilinguals. We propose that learning and actively using an L2
      after childhood can have rapid dynamic effects on WM structure, which in turn may
      assist in preserving WM integrity in older age. 

PMID- 25583504
TI  - Ventral aspect of the visual form pathway is not critical for the perception of
      biological motion.
AB  - Identifying the movements of those around us is fundamental for many daily
      activities, such as recognizing actions, detecting predators, and interacting
      with others socially. A key question concerns the neurobiological substrates
      underlying biological motion perception. Although the ventral "form" visual
      cortex is standardly activated by biologically moving stimuli, whether these
      activations are functionally critical for biological motion perception or are
      epiphenomenal remains unknown. To address this question, we examined whether
      focal damage to regions of the ventral visual cortex, resulting in significant
      deficits in form perception, adversely affects biological motion perception. Six
      patients with damage to the ventral cortex were tested with sensitive point-light
      display paradigms. All patients were able to recognize unmasked point-light
      displays and their perceptual thresholds were not significantly different from
      those of three different control groups, one of which comprised brain-damaged
      patients with spared ventral cortex (n > 50). Importantly, these six patients
      performed significantly better than patients with damage to regions critical for
      biological motion perception. To assess the necessary contribution of different
      regions in the ventral pathway to biological motion perception, we complement the
      behavioral findings with a fine-grained comparison between the lesion location
      and extent, and the cortical regions standardly implicated in biological motion
      processing. This analysis revealed that the ventral aspects of the form pathway
      (e.g., fusiform regions, ventral extrastriate body area) are not critical for
      biological motion perception. We hypothesize that the role of these ventral
      regions is to provide enhanced multiview/posture representations of the moving
      person rather than to represent biological motion perception per se. 

PMID- 25583507
TI  - Computer-based personality judgments are more accurate than those made by humans.
AB  - Judging others' personalities is an essential skill in successful social living,
      as personality is a key driver behind people's interactions, behaviors, and
      emotions. Although accurate personality judgments stem from social-cognitive
      skills, developments in machine learning show that computer models can also make
      valid judgments. This study compares the accuracy of human and computer-based
      personality judgments, using a sample of 86,220 volunteers who completed a 100
      item personality questionnaire. We show that (i) computer predictions based on a
      generic digital footprint (Facebook Likes) are more accurate (r = 0.56) than
      those made by the participants' Facebook friends using a personality
      questionnaire (r = 0.49); (ii) computer models show higher interjudge agreement;
      and (iii) computer personality judgments have higher external validity when
      predicting life outcomes such as substance use, political attitudes, and physical
      health; for some outcomes, they even outperform the self-rated personality
      scores. Computers outpacing humans in personality judgment presents significant
      opportunities and challenges in the areas of psychological assessment, marketing,
      and privacy. 

PMID- 25583506
TI  - Visualization of the type III secretion sorting platform of Shigella flexneri.
AB  - Bacterial type III secretion machines are widely used to inject virulence
      proteins into eukaryotic host cells. These secretion machines are evolutionarily
      related to bacterial flagella and consist of a large cytoplasmic complex, a
      transmembrane basal body, and an extracellular needle. The cytoplasmic complex
      forms a sorting platform essential for effector selection and needle assembly,
      but it remains largely uncharacterized. Here we use high-throughput cryoelectron
      tomography (cryo-ET) to visualize intact machines in a virulent Shigella flexneri
      strain genetically modified to produce minicells capable of interaction with host
      cells. A high-resolution in situ structure of the intact machine determined by
      subtomogram averaging reveals the cytoplasmic sorting platform, which consists of
      a central hub and six spokes, with a pod-like structure at the terminus of each
      spoke. Molecular modeling of wild-type and mutant machines allowed us to propose
      a model of the sorting platform in which the hub consists mainly of a hexamer of
      the Spa47 ATPase, whereas the MxiN protein comprises the spokes and the Spa33
      protein forms the pods. Multiple contacts among those components are essential to
      align the Spa47 ATPase with the central channel of the MxiA protein export gate
      to form a unique nanomachine. The molecular architecture of the Shigella type III
      secretion machine and its sorting platform provide the structural foundation for
      further dissecting the mechanisms underlying type III secretion and pathogenesis
      and also highlight the major structural distinctions from bacterial flagella. 

PMID- 25583508
TI  - Global typology of urban energy use and potentials for an urbanization mitigation
      wedge.
AB  - The aggregate potential for urban mitigation of global climate change is
      insufficiently understood. Our analysis, using a dataset of 274 cities
      representing all city sizes and regions worldwide, demonstrates that economic
      activity, transport costs, geographic factors, and urban form explain 37% of
      urban direct energy use and 88% of urban transport energy use. If current trends
      in urban expansion continue, urban energy use will increase more than threefold,
      from 240 EJ in 2005 to 730 EJ in 2050. Our model shows that urban planning and
      transport policies can limit the future increase in urban energy use to 540 EJ in
      2050 and contribute to mitigating climate change. However, effective policies for
      reducing urban greenhouse gas emissions differ with city type. The results show
      that, for affluent and mature cities, higher gasoline prices combined with
      compact urban form can result in savings in both residential and transport energy
      use. In contrast, for developing-country cities with emerging or nascent
      infrastructures, compact urban form, and transport planning can encourage higher
      population densities and subsequently avoid lock-in of high carbon emission
      patterns for travel. The results underscore a significant potential urbanization
      wedge for reducing energy use in rapidly urbanizing Asia, Africa, and the Middle
      East. 

PMID- 25583511
TI  - Ironing out carbon export to the deep ocean.

PMID- 25583509
TI  - Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious
      hypothalamic neurogenesis in embryonic zebrafish.
AB  - Bisphenol A (BPA), a ubiquitous endocrine disruptor that is present in many
      household products, has been linked to obesity, cancer, and, most relevant here,
      childhood neurological disorders such as anxiety and hyperactivity. However, how
      BPA exposure translates into these neurodevelopmental disorders remains poorly
      understood. Here, we used zebrafish to link BPA mechanistically to disease
      etiology. Strikingly, treatment of embryonic zebrafish with very low-dose BPA
      (0.0068 MUM, 1,000-fold lower than the accepted human daily exposure) and
      bisphenol S (BPS), a common analog used in BPA-free products, resulted in 180%
      and 240% increases, respectively, in neuronal birth (neurogenesis) within the
      hypothalamus, a highly conserved brain region involved in hyperactivity.
      Furthermore, restricted BPA/BPS exposure specifically during the neurogenic
      window caused later hyperactive behaviors in zebrafish larvae. Unexpectedly, we
      show that BPA-mediated precocious neurogenesis and the concomitant behavioral
      phenotype were not dependent on predicted estrogen receptors but relied on
      androgen receptor-mediated up-regulation of aromatase. Although human
      epidemiological results are still emerging, an association between high maternal
      urinary BPA during gestation and hyperactivity and other behavioral disturbances
      in the child has been suggested. Our studies here provide mechanistic support
      that the neurogenic period indeed may be a window of vulnerability and uncovers
      previously unexplored avenues of research into how endocrine disruptors might
      perturb early brain development. Furthermore, our results show that BPA-free
      products are not necessarily safer and support the removal of all bisphenols from
      consumer merchandise. 

PMID- 25583512
TI  - Magnetostrophic balance as the optimal state for turbulent magnetoconvection.
AB  - The magnetic fields of Earth and other planets are generated by turbulent
      convection in the vast oceans of liquid metal within them. Although direct
      observation is not possible, this liquid metal circulation is thought to be
      dominated by the controlling influences of planetary rotation and magnetic fields
      through the Coriolis and Lorentz forces. Theory famously predicts that planetary
      dynamo systems naturally settle into the so-called magnetostrophic state, where
      the Coriolis and Lorentz forces partially cancel, and convection is optimally
      efficient. Although this magnetostrophic theory correctly predicts the strength
      of Earth's magnetic field, no laboratory experiments have reached the
      magnetostrophic regime in turbulent liquid metal convection. Furthermore,
      computational dynamo simulations have as yet failed to produce a magnetostrophic
      dynamo, which has led some to question the existence of the magnetostrophic
      state. Here, we present results from the first, to our knowledge, turbulent,
      magnetostrophic convection experiments using the liquid metal gallium. We find
      that turbulent convection in the magnetostrophic regime is, in fact, maximally
      efficient. The experimental results clarify these previously disparate results,
      suggesting that the dynamically optimal magnetostrophic state is the natural
      expression of turbulent planetary dynamo systems. 

PMID- 25583510
TI  - An HD-domain phosphodiesterase mediates cooperative hydrolysis of c-di-AMP to
      affect bacterial growth and virulence.
AB  - The nucleotide cyclic di-3',5'- adenosine monophosphate (c-di-AMP) was recently
      identified as an essential and widespread second messenger in bacterial
      signaling. Among c-di-AMP-producing bacteria, altered nucleotide levels result in
      several physiological defects and attenuated virulence. Thus, a detailed
      molecular understanding of c-di-AMP metabolism is of both fundamental and
      practical interest. Currently, c-di-AMP degradation is recognized solely among
      DHH-DHHA1 domain-containing phosphodiesterases. Using chemical proteomics, we
      identified the Listeria monocytogenes protein PgpH as a molecular target of c-di
      AMP. Biochemical and structural studies revealed that the PgpH His-Asp (HD)
      domain bound c-di-AMP with high affinity and specifically hydrolyzed this
      nucleotide to 5'-pApA. PgpH hydrolysis activity was inhibited by ppGpp,
      indicating a cross-talk between c-di-AMP signaling and the stringent response.
      Genetic analyses supported coordinated regulation of c-di-AMP levels in and out
      of the host. Intriguingly, a L. monocytogenes mutant that lacks c-di-AMP
      phosphodiesterases exhibited elevated c-di-AMP levels, hyperinduced a host type-I
      IFN response, and was significantly attenuated for infection. Furthermore, PgpH
      homologs, which belong to the 7TMR-HD family, are widespread among hundreds of c
      di-AMP synthesizing microorganisms. Thus, PgpH represents a broadly conserved
      class of c-di-AMP phosphodiesterase with possibly other physiological functions
      in this crucial signaling network. 

PMID- 25583513
TI  - Reduced autophagy in livers of fasted, fat-depleted, ghrelin-deficient mice:
      reversal by growth hormone.
AB  - Plasma growth hormone (GH) and hepatic autophagy each have been reported to
      protect against hypoglycemia in the fasted state, but previous data have not
      linked the two. Here we demonstrate a connection using a mouse model of fasting
      in a fat-depleted state. Mice were subjected to 1 wk of 60% calorie restriction,
      causing them to lose nearly all body fat. They were then fasted for 23 h. During
      fasting, WT mice developed massive increases in plasma GH and a concomitant
      increase in hepatic autophagy, allowing them to maintain viable levels of blood
      glucose. In contrast, lethal hypoglycemia occurred in mice deficient in the GH
      secretagogue ghrelin as a result of knockout of the gene encoding ghrelin O
      acyltransferase (GOAT), which catalyzes a required acylation of the peptide.
      Fasting fat-depleted Goat(-/-) mice showed a blunted increase in GH and a marked
      decrease in hepatic autophagy. Restoration of GH by infusion during the week of
      calorie restriction maintained autophagy in the Goat(-/-) mice and prevented
      lethal hypoglycemia. Acute injections of GH after 7 d of calorie restriction also
      restored hepatic autophagy, but failed to increase blood glucose, perhaps owing
      to ATP deficiency in the liver. These data indicate that GH stimulation of
      autophagy is necessary over the long term, but not sufficient over the short term
      to maintain blood glucose levels in fasted, fat-depleted mice. 

PMID- 25583514
TI  - Impaired Hippo signaling promotes Rho1-JNK-dependent growth.
AB  - The Hippo and c-Jun N-terminal kinase (JNK) pathway both regulate growth and
      contribute to tumorigenesis when dysregulated. Whereas the Hippo pathway acts via
      the transcription coactivator Yki/YAP to regulate target gene expression, JNK
      signaling, triggered by various modulators including Rho GTPases, activates the
      transcription factors Jun and Fos. Here, we show that impaired Hippo signaling
      induces JNK activation through Rho1. Blocking Rho1-JNK signaling suppresses Yki
      induced overgrowth in the wing disk, whereas ectopic Rho1 expression promotes
      tissue growth when apoptosis is prohibited. Furthermore, Yki directly regulates
      Rho1 transcription via the transcription factor Sd. Thus, our results have
      identified a novel molecular link between the Hippo and JNK pathways and
      implicated the essential role of the JNK pathway in Hippo signaling-related
      tumorigenesis. 

PMID- 25583516
TI  - Physical and virtual water transfers for regional water stress alleviation in
      China.
AB  - Water can be redistributed through, in physical terms, water transfer projects
      and virtually, embodied water for the production of traded products. Here, we
      explore whether such water redistributions can help mitigate water stress in
      China. This study, for the first time to our knowledge, both compiles a full
      inventory for physical water transfers at a provincial level and maps virtual
      water flows between Chinese provinces in 2007 and 2030. Our results show that, at
      the national level, physical water flows because of the major water transfer
      projects amounted to 4.5% of national water supply, whereas virtual water flows
      accounted for 35% (varies between 11% and 65% at the provincial level) in 2007.
      Furthermore, our analysis shows that both physical and virtual water flows do not
      play a major role in mitigating water stress in the water-receiving regions but
      exacerbate water stress for the water-exporting regions of China. Future water
      stress in the main water-exporting provinces is likely to increase further based
      on our analysis of the historical trajectory of the major governing socioeconomic
      and technical factors and the full implementation of policy initiatives relating
      to water use and economic development. Improving water use efficiency is key to
      mitigating water stress, but the efficiency gains will be largely offset by the
      water demand increase caused by continued economic development. We conclude that
      much greater attention needs to be paid to water demand management rather than
      the current focus on supply-oriented management. 

PMID- 25583515
TI  - Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and
      relaxation.
AB  - BDNF and its associated tropomyosin-related kinase receptor B (TrkB) nurture
      vessels and nerves serving the heart. However, the direct effect of BDNF/TrkB
      signaling on the myocardium is poorly understood. Here we report that cardiac
      specific TrkB knockout mice (TrkB(-/-)) display impaired cardiac contraction and
      relaxation, showing that BDNF/TrkB signaling acts constitutively to sustain in
      vivo myocardial performance. BDNF enhances normal cardiomyocyte Ca(2+) cycling,
      contractility, and relaxation via Ca(2+)/calmodulin-dependent protein kinase II
      (CaMKII). Conversely, failing myocytes, which have increased truncated TrkB
      lacking tyrosine kinase activity and chronically activated CaMKII, are
      insensitive to BDNF. Thus, BDNF/TrkB signaling represents a previously
      unidentified pathway by which the peripheral nervous system directly and
      tonically influences myocardial function in parallel with beta-adrenergic
      control. Deficits in this system are likely additional contributors to acute and
      chronic cardiac dysfunction. 

PMID- 25583517
TI  - Giant reversible, facet-dependent, structural changes in a correlated-electron
      insulator induced by ionic liquid gating.
AB  - The use of electric fields to alter the conductivity of correlated electron
      oxides is a powerful tool to probe their fundamental nature as well as for the
      possibility of developing novel electronic devices. Vanadium dioxide (VO2) is an
      archetypical correlated electron system that displays a temperature-controlled
      insulating to metal phase transition near room temperature. Recently, ionic
      liquid gating, which allows for very high electric fields, has been shown to
      induce a metallic state to low temperatures in the insulating phase of
      epitaxially grown thin films of VO2. Surprisingly, the entire film becomes
      electrically conducting. Here, we show, from in situ synchrotron X-ray
      diffraction and absorption experiments, that the whole film undergoes giant,
      structural changes on gating in which the lattice expands by up to ~3% near room
      temperature, in contrast to the 10 times smaller (~0.3%) contraction when the
      system is thermally metallized. Remarkably, these structural changes are fully
      reversible on reverse gating. Moreover, we find these structural changes and the
      concomitant metallization are highly dependent on the VO2 crystal facet, which we
      relate to the ease of electric-field-induced motion of oxygen ions along chains
      of edge-sharing VO6 octahedra that exist along the (rutile) c axis. 

PMID- 25583519
TI  - Do sixth-grade writers need process strategies?
AB  - BACKGROUND: Strategy-focused writing instruction trains students both to set
      explicit product goals and to adopt specific procedural strategies, particularly
      for planning text. A number of studies have demonstrated that strategy-focused
      writing instruction is effective in developing writing performance. AIM: This
      study aimed to determine whether teaching process strategies provides additional
      benefit over teaching students to set product goals. SAMPLE: Ninety-four
      typically developing Spanish sixth-grade (upper primary) students. METHOD:
      Students received 10 hr of instruction in one of three conditions: Strategy
      focused training in setting product goals and in writing procedures (planning and
      revision; Product-and-Process), strategy-focused training in setting product
      goals (Product-Only), and product-focused instruction (Control). Students'
      writing performance was assessed before, during, and after intervention with
      process measures based on probed self-report and holistic and text-analytic
      measures of text quality. RESULTS: Training that included process instruction was
      successful in changing students' writing processes, with no equivalent process
      changes in the Product-Only or Control conditions. Both Process-and-Product and
      Product-Only conditions resulted in substantial improvements in the quality of
      students' texts relative to controls, but with no evidence of benefits of process
      instruction over those provided by the Product-Only condition. Teaching process
      substantially increased time-on-task. CONCLUSIONS: Our findings confirm the value
      of strategy-focused writing instruction, but question the value of training
      specific process strategies.

PMID- 25583518
TI  - Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is
      crucial for Plasmodium falciparum erythrocyte invasion.
AB  - Erythrocyte invasion by Plasmodium falciparum merozoites is a highly intricate
      process in which Plasmodium falciparum reticulocyte binding-like homologous
      protein 5 (PfRH5) is an indispensable parasite ligand that binds with its
      erythrocyte receptor, Basigin. PfRH5 is a leading blood-stage vaccine candidate
      because it exhibits limited polymorphisms and elicits potent strain-transcending
      parasite neutralizing antibodies. However, the mechanism by which it is anchored
      to the merozoite surface remains unknown because both PfRH5 and the PfRH5
      interacting protein (PfRipr) lack transmembrane domains and GPI anchors. Here we
      have identified a conserved GPI-linked parasite protein, Cysteine-rich protective
      antigen (CyRPA) as an interacting partner of PfRH5-PfRipr that tethers the
      PfRH5/PfRipr/CyRPA multiprotein complex on the merozoite surface. CyRPA was
      demonstrated to be GPI-linked, localized in the micronemes, and essential for
      erythrocyte invasion. Specific antibodies against the three proteins successfully
      detected the intact complex in the parasite and coimmunoprecipitated the three
      interacting partners. Importantly, full-length CyRPA antibodies displayed potent
      strain-transcending invasion inhibition, as observed for PfRH5. CyRPA does not
      bind with erythrocytes, suggesting that its parasite neutralizing antibodies
      likely block its critical interaction with PfRH5-PfRipr, leading to a blockade of
      erythrocyte invasion. Further, CyRPA and PfRH5 antibody combinations produced
      synergistic invasion inhibition, suggesting that simultaneous blockade of the
      PfRH5-Basigin and PfRH5/PfRipr/CyRPA interactions produced an enhanced inhibitory
      effect. Our discovery of the critical interactions between PfRH5, PfRipr, and the
      GPI-anchored CyRPA clearly defines the components of the essential PfRH5 adhesion
      complex for P. falciparum erythrocyte invasion and offers it as a previously
      unidentified potent target for antimalarial strategies that could abrogate
      formation of the crucial multiprotein complex. 

PMID- 25583520
TI  - The biological clock and the molecular basis of lysosomal storage diseases.
AB  - The lysosomal storage disorders encompass nearly fifty diseases provoked by lack
      or deficiency of enzymes essential for the breakdown of complex molecules and
      hallmarked by accumulation in the lysosomes of metabolic residues. Histochemistry
      and cytochemistry studies evidenced patterns of circadian variation of the
      lysosomal marker enzymes, suggesting that lysosomal function oscillates
      rhythmically during the 24-h day. The circadian rhythmicity of cellular processes
      is driven by the biological clock ticking through transcriptional/translational
      feedback loops hardwired by circadian genes and proteins. Malfunction of the
      molecular clockwork may provoke severe deregulation of downstream gene expression
      regulating a complex array of cellular functions leading to anatomical and
      functional changes. In this review we highlight that all the genes mutated in
      lysosomal storage disorders encode circadian transcripts suggesting a direct
      participation of the biological clock in the pathophysiological mechanisms
      underlying cellular and tissue derangements hallmarking these hereditary
      diseases. The 24-h periodicity of oscillation of gene transcription and
      translation could lead in physiological conditions to circadian rhythmicity of
      fluctuation of enzyme levels and activity, so that gene transfer could be
      envisaged to reproduce 24-h periodicity of variation of enzymatic dynamics and
      circadian rhythmicity could have an impact on the schedule of enzyme replacement
      therapy. 

PMID- 25583521
TI  - Streptococcus pyogenes malate degradation pathway links pH regulation and
      virulence.
AB  - The ability of Streptococcus pyogenes to infect different niches within its human
      host most likely relies on its ability to utilize alternative carbon sources. In
      examining this question, we discovered that all sequenced S. pyogenes strains
      possess the genes for the malic enzyme (ME) pathway, which allows malate to be
      used as a supplemental carbon source for growth. ME is comprised of four genes in
      two adjacent operons, with the regulatory two-component MaeKR required for
      expression of genes encoding a malate permease (maeP) and malic enzyme (maeE).
      Analysis of transcription indicated that expression of maeP and maeE is induced
      by both malate and low pH, and induction in response to both cues is dependent on
      the MaeK sensor kinase. Furthermore, both maePE and maeKR are repressed by
      glucose, which occurs via a CcpA-independent mechanism. Additionally, malate
      utilization requires the PTS transporter EI enzyme (PtsI), as a PtsI(-) mutant
      fails to express the ME genes and is unable to utilize malate. Virulence of
      selected ME mutants was assessed in a murine model of soft tissue infection.
      MaeP(-), MaeK(-), and MaeR(-) mutants were attenuated for virulence, whereas a
      MaeE(-) mutant showed enhanced virulence compared to that of the wild type. Taken
      together, these data show that ME contributes to S. pyogenes' carbon source
      repertory, that malate utilization is a highly regulated process, and that a
      single regulator controls ME expression in response to diverse signals.
      Furthermore, malate uptake and utilization contribute to the adaptive pH
      response, and ME can influence the outcome of infection. 

PMID- 25583522
TI  - A small molecule, odanacatib, inhibits inflammation and bone loss caused by
      endodontic disease.
AB  - Periapical disease, an inflammatory disease mainly caused by dental caries, is
      one of the most prevalent infectious diseases of humans, affecting both children
      and adults. The infection travels through the root, leading to inflammation, bone
      destruction, and severe pain for the patient. Therefore, the development of a new
      class of anti-periapical disease therapies is necessary and critical for
      treatment and prevention. A small molecule, odanacatib (ODN), which is a
      cathepsin K (Ctsk) inhibitor, was investigated to determine its ability to treat
      this disease in a mouse model of periapical disease. While Ctsk was originally
      found in osteoclasts as an osteoclast-specific lysosomal protease, we were
      surprised to find that ODN can suppress the bacterium-induced immune response as
      well as bone destruction in the lesion area. X rays and microcomputed tomography
      (micro-CT) showed that ODN treatment had significant bone protection effects at
      different time points. Immunohistochemical and immunofluorescent staining show
      that ODN treatment dramatically decreased F4/80+ macrophages and CD3+ T cells in
      the lesion areas 42 days after infection. Consistent with these findings,
      quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay
      (ELISA) analysis showed low levels of proinflammatory mRNAs (for tumor necrosis
      factor alpha, interleukin 6, and interleukin 23alpha) and corresponding cytokine
      expression in the ODN-treated disease group. The levels of mRNA for Toll-like
      receptors 4, 5, and 9 also largely decreased in the ODN-treated disease group.
      Our results demonstrated that ODN can inhibit endodontic disease development,
      bone erosion, and immune response. These results indicate that application of
      this small molecule offers a new opportunity to design effective therapies that
      could prevent periapical inflammation and revolutionize current treatment
      options.

PMID- 25583523
TI  - Polymyxin B resistance and biofilm formation in Vibrio cholerae are controlled by
      the response regulator CarR.
AB  - Two-component systems play important roles in the physiology of many bacterial
      pathogens. Vibrio cholerae's CarRS two-component regulatory system negatively
      regulates expression of vps (Vibrio polysaccharide) genes and biofilm formation.
      In this study, we report that CarR confers polymyxin B resistance by positively
      regulating expression of the almEFG genes, whose products are required for
      glycine and diglycine modification of lipid A. We determined that CarR directly
      binds to the regulatory region of the almEFG operon. Similarly to a carR mutant,
      strains lacking almE, almF, and almG exhibited enhanced polymyxin B sensitivity.
      We also observed that strains lacking almE or the almEFG operon have enhanced
      biofilm formation. Our results reveal that CarR regulates biofilm formation and
      antimicrobial peptide resistance in V. cholerae. 

PMID- 25583524
TI  - Innate immunity induced by Plasmodium liver infection inhibits malaria
      reinfections.
AB  - Following transmission through a mosquito bite to the mammalian host, Plasmodium
      parasites first invade and replicate inside hepatocytes before infecting
      erythrocytes and causing malaria. The mechanisms limiting Plasmodium reinfections
      in humans living in regions of malaria endemicity have mainly been explored by
      studying the resistance induced by the blood stage of infection. However,
      epidemiologic studies have suggested that in high-transmission areas,
      preerythrocytic stages also activate host resistance to reinfection. This, along
      with the recent discovery that liver infections trigger a specific and effective
      type I interferon (IFN) response, prompted us to hypothesize that this pre
      erythrocyte-stage-induced resistance is linked to liver innate immunity. Here, we
      combined experimental approaches and mathematical modeling to recapitulate field
      studies and understand the molecular basis behind such resistance. We present a
      newly established mouse reinfection model and demonstrate that rodent malaria
      liver-stage infection inhibits reinfection. This protection relies on the
      activation of innate immunity and involves the type I IFN response and the
      antimicrobial cytokine gamma IFN (IFN-gamma). Importantly, mathematical
      simulations indicate that the predictions based on our experimental murine
      reinfection model fit available epidemiological data. Overall, our study revealed
      that liver-stage-induced innate immunity may contribute to the preerythrocytic
      resistance observed in humans in regions of malaria hyperendemicity. 

PMID- 25583525
TI  - Importance of bacterial replication and alveolar macrophage-independent clearance
      mechanisms during early lung infection with Streptococcus pneumoniae.
AB  - Although the importance of alveolar macrophages for host immunity during early
      Streptococcus pneumoniae lung infection is well established, the contribution and
      relative importance of other innate immunity mechanisms and of bacterial factors
      are less clear. We have used a murine model of S. pneumoniae early lung infection
      with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant
      TIGR4 strains to assess the effects of inoculum size, bacterial replication,
      capsule, and alveolar macrophage-dependent and -independent clearance mechanisms
      on bacterial persistence within the lungs. Alveolar macrophage-dependent and 
      independent (calculated indirectly) clearance half-lives and bacterial
      replication doubling times were estimated using a mathematical model. In this
      model, after infection with a high-dose inoculum of encapsulated S. pneumoniae,
      alveolar macrophage-independent clearance mechanisms were dominant, with a
      clearance half-life of 24 min compared to 135 min for alveolar macrophage
      dependent clearance. In addition, after a high-dose inoculum, successful lung
      infection required rapid bacterial replication, with an estimated S. pneumoniae
      doubling time of 16 min. The capsule had wide effects on early lung clearance
      mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent
      and 31 min for alveolar macrophage-dependent clearance of unencapsulated
      bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time
      increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance
      half-life improved to 42 min and was largely unaffected by the capsule. These
      data demonstrate the large effects of bacterial factors (inoculum size, the
      capsule, and rapid replication) and alveolar macrophage-independent clearance
      mechanisms during early lung infection with S. pneumoniae. 

PMID- 25583526
TI  - 5-Lipoxygenase negatively regulates Th1 response during Brucella abortus
      infection in mice.
AB  - Brucella abortus is a Gram-negative bacterium that infects humans and cattle,
      causing a chronic inflammatory disease known as brucellosis. A Th1-mediated
      immune response plays a critical role in host control of this pathogen. Recent
      findings indicate contrasting roles for lipid mediators in host responses against
      infections. 5-Lipoxygenase (5-LO) is an enzyme required for the production of the
      lipid mediators leukotrienes and lipoxins. To determine the involvement of 5-LO
      in host responses to B. abortus infection, we intraperitoneally infected wild
      type and 5-LO-deficient mice and evaluated the progression of infection and
      concomitant expression of immune mediators. Here, we demonstrate that B. abortus
      induced the upregulation of 5-LO mRNA in wild-type mice. Moreover, this pathogen
      upregulated the production of the lipid mediators leukotriene B4 and lipoxin A4
      in a 5-LO-dependent manner. 5-LO-deficient mice displayed lower bacterial burdens
      in the spleen and liver and less severe liver pathology, demonstrating an
      enhanced resistance to infection. Host resistance paralleled an increased
      expression of the proinflammatory mediators interleukin-12 (IL-12), gamma
      interferon (IFN-gamma), and inducible nitric oxide synthase (iNOS) during the
      course of infection. Moreover, we demonstrated that 5-LO downregulated the
      expression of IL-12 in macrophages during B. abortus infection. Our results
      suggest that 5-LO has a major involvement in B. abortus infection, by functioning
      as a negative regulator of the protective Th1 immune responses against this
      pathogen. 

PMID- 25583527
TI  - MyD88-dependent signaling drives host survival and early cytokine production
      during Histoplasma capsulatum infection.
AB  - The ability of the innate immune system to trigger an adaptive T cell response is
      critical to resolution of infection with the fungal pathogen Histoplasma
      capsulatum. However, the signaling pathways and cell types involved in the
      recognition of and response to this respiratory pathogen remain poorly defined.
      Here, we show that MyD88, an adaptor protein vital to multiple innate immune
      pathways, is critically required for the host response to Histoplasma. MyD88
      deficient (MyD88-/-) mice are unable to control the fungal burden and are more
      sensitive to Histoplasma infection than wild-type, Dectin-1-/-, or interleukin 1
      receptor-deficient (IL-1R-/-) mice. We found that MyD88 is necessary for the
      production of key early inflammatory cytokines and the subsequent recruitment of
      inflammatory monocytes to the lung. In both our in vitro and ex vivo analyses,
      MyD88 was intrinsically required in dendritic cells and alveolar macrophages for
      initial cytokine production. Additionally, MyD88-deficient bone marrow-derived
      dendritic cells fail to efficiently control fungal growth when cocultured with
      primed splenic T cells. Surprisingly, mice that lack MyD88 only in dendritic
      cells and alveolar macrophages are competent for early cytokine production and
      normal survival, indicating the presence of compensatory and redundant MyD88
      signaling in other cell types during infection. Ultimately, global MyD88
      deficiency prevents proper T cell activation and gamma interferon (IFN-gamma)
      production, which are critical for infection resolution. Collectively, this work
      reveals a central role for MyD88 in coordinating the innate and adaptive immune
      responses to infection with this ubiquitous fungal pathogen of humans.

PMID- 25583528
TI  - Resistance of Neisseria meningitidis to human serum depends on T and B cell
      stimulating protein B.
AB  - The ability of the human bacterial pathogen Neisseria meningitidis to cause
      invasive disease depends on survival in the bloodstream via mechanisms to
      suppress complement activation. In this study, we show that prophage genes coding
      for T and B cell stimulating protein B (TspB), which is an immunoglobulin-binding
      protein, are essential for survival of N. meningitidis group B strain H44/76 in
      normal human serum (NHS). H44/76 carries three genes coding for TspB. Mutants
      having all tspB genes inactivated did not survive in >5% NHS or IgG-depleted NHS.
      TspB appeared to inhibit IgM-mediated activation of the classical complement
      pathway, since survival of the tspB triple knockout was the same as that of the
      parent strain or a complemented mutant when the classical pathway was inactivated
      by depleting NHS of C1q and was increased in IgM-depleted NHS. A mutant solely
      carrying tspB gene nmbh4476_0681 was as resistant as the parent strain, while
      mutants carrying only nmbh4476_0598 or nmbh4476_1698 were killed in >=5% NHS. The
      phenotype associated with TspB is formation of a matrix containing TspB, IgG, and
      DNA that envelopes aggregates of bacteria. Recombinant proteins corresponding to
      particular subdomains of TspB were found to have human IgG Fcgamma- and/or DNA
      binding activity, but only TspB derivatives containing both domains formed large,
      biofilm-like aggregates when combined with purified IgG and DNA. Recognizing the
      role of TspB in serum resistance may lead to a better understanding of why
      strains that carry tspB genes are associated with invasive meningococcal disease.

PMID- 25583530
TI  - Comaneci neck bridging device for the treatment of cerebral aneurysms.
AB  - BACKGROUND AND PURPOSE: Adjunctive devices are commonly employed in the treatment
      of wide necked cerebral aneurysms. Balloon remodeling and permanent stent
      implantation may lead to thromboembolic complications or the need for
      antiplatelet use. A temporary stent that does not lead to complete flow arrest
      may be beneficial. METHODS: We studied 20 New Zealand white rabbits in whom
      aneurysms were created using elastase and ligation of the right common carotid
      artery. The aneurysms were then embolized with bare platinum coils along with
      adjunctive treatment using the Comaneci device or the Hyperglide balloon.
      Assessments were made for endothelial injury using scanning electron microscopy
      (SEM) and light microscopy. RESULTS: 20 rabbits of mean+/-SD weight 3.1+/-0.2 kg
      were studied. Twelve rabbits were treated with the Comaneci device and eight with
      the Hyperglide balloon. There were no substantial differences on SEM or light
      microscopy in the subacute and chronic phase to suggest the Comaneci device
      caused endothelial injury. CONCLUSIONS: The Comaneci device is a new adjuvant
      treatment for bridging of wide necked aneurysms with the advantage of averting
      flow arrest during deployment. There does not appear to be any evidence of
      significant endothelial damage during deployment in preclinical studies.

PMID- 25583529
TI  - Photobacterium damselae subsp. damselae major virulence factors Dly, plasmid
      encoded HlyA, and chromosome-encoded HlyA are secreted via the type II secretion
      system.
AB  - Photobacterium damselae subsp. damselae is a marine bacterium that causes
      septicemia in marine animals and in humans. Previously, we had determined a major
      role of pPHDD1 plasmid-encoded Dly (damselysin) and HlyA (HlyApl) and the
      chromosome-encoded HlyA (HlyAch) hemolysins in virulence. However, the mechanisms
      by which these toxins are secreted remain unknown. In this study, we found that a
      mini-Tn10 transposon mutant in a plasmidless strain showing an impaired hemolytic
      phenotype contained an insertion in epsL, a component of a type II secretion
      system (T2SS). Reconstruction of the mutant by allelic exchange confirmed the
      specific involvement of epsL in HlyAch secretion. In addition, mutation of epsL
      in a pPHDD1-harboring strain caused an almost complete abolition of hemolytic
      activity against sheep erythrocytes, indicating that epsL plays a major role in
      secretion of the plasmid-encoded HlyApl and Dly. This was further demonstrated by
      analysis of different combinations of hemolysin gene mutants and by strain-strain
      complementation assays. We also found that mutation of the putative prepilin
      peptidase gene pilD severely affected hemolysis, which dropped at levels inferior
      to those of epsL mutants. Promoter expression analyses suggested that impairment
      of hemolysin secretion in epsL and pilD mutants might constitute a signal that
      affects hemolysin and T2SS gene expression at the transcriptional level. In
      addition, single epsL and pilD mutations caused a drastic decrease in virulence
      for mice, demonstrating a major role of T2SS and pilD in P. damselae subsp.
      damselae virulence. 

PMID- 25583531
TI  - 4D DSA a new technique for arteriovenous malformation evaluation: a feasibility
      study.
AB  - BACKGROUND: The angioarchitectural features of an arteriovenous malformation
      (AVM) provide key information regarding natural history and treatment planning.
      Because of rapid filling and vascular overlap, two-dimensional (2D) and three
      dimensional (3D) digital subtraction angiography (DSA) are often suboptimal for
      evaluation of these features. We have developed an algorithm that derives a
      series of fully time-resolved 3D DSA volumes (four-dimensional (4D) DSA) at up to
      30 frames/s from a conventional 3D DSA. The temporal/spatial resolution of 4D
      reconstructions is significantly higher than that provided by current MR
      angiography and CT angiography techniques. 4D reconstruction allows viewing of an
      AVM from any angle at any time during its opacification. This feasibility study
      investigated the potential of 4D DSA to improve the ability to analyze
      angioarchitectural features compared with conventional 2D and 3D DSA. METHODS:
      2D, 3D, and 4D DSA reconstructions of angiographic studies of six AVMs were
      evaluated by three cerebrovascular neurosurgeons and one interventional
      neuroradiologist. These observers evaluated the ability of each modality to
      visualize the angioarchitectural features of the AVMs. They also compared the
      information provided using the combination of 2D and 3D DSA with that provided by
      a 4D DSA reconstruction. RESULTS: By consensus, 4D DSA provided the best ability
      to visualize the internal features of the AVM including intranidal aneurysms,
      fistulae, venous obstructions, and sequence of filling and draining. 2D and 3D
      images in comparison were limited because of overlap of the vasculature.
      CONCLUSIONS: In this small series, 4D DSA provided better ability to visualize
      the angioarchitecture of an AVM than conventional methods. Further experience is
      required to determine the ultimate utility of this technique.

PMID- 25583532
TI  - A predictive model of hospitalization cost after cerebral aneurysm clipping.
AB  - BACKGROUND: Cost containment is the cornerstone of the Affordable Care Act.
      Although studies have compared the cost of cerebral aneurysm clipping (CAC) and
      coiling, they have not focused on identification of drivers of cost after CAC, or
      prediction of its magnitude. The objective of the present study was to develop
      and validate a predictive model of hospitalization cost after CAC. METHODS: We
      performed a retrospective study involving CAC patients who were registered in the
      Nationwide Inpatient Sample (NIS) database from 2005 to 2010. The two cohorts of
      ruptured and unruptured aneurysms underwent 1:1 randomization to create
      derivation and validation subsamples. Regression techniques were used for the
      creation of a parsimonious predictive model. RESULTS: Of the 7798 patients
      undergoing CAC, 4505 (58%) presented with unruptured and 3293 (42%) with ruptured
      aneurysms. Median hospitalization cost was US$24,398 (IQR $17,079 to $38,249) and
      $73,694 (IQR $46,270 to $115,128) for the two cohorts, respectively. Common
      drivers of cost identified in the multivariate analyses included the following:
      length of stay, number of admission diagnoses and procedures, hospital size and
      region, and patient income. The models were validated in independent cohorts and
      demonstrated final R(2) values very similar to the initial models. The predicted
      and observed values in the validation cohort demonstrated good correlation.
      CONCLUSIONS: This national study identified significant drivers of
      hospitalization cost after CAC. The presented model can be utilized as an adjunct
      in the cost containment debate and the creation of data driven policies.

PMID- 25583533
TI  - Direct aspiration first pass technique for the treatment of acute ischemic
      stroke: initial experience at a European stroke center.
AB  - INTRODUCTION: Over the past decade, endovascular techniques for the treatment of
      acute ischemic stroke have emerged significantly. However, revascularization
      rates are limited at approximately 80%, and mechanical thrombectomy procedures
      still last about 1 h. Therefore, we investigated the novel direct aspiration
      first pass technique for its efficacy and safety. METHODS: Our
      neurointerventional database was screened for patients who received mechanical
      thrombectomy for acute ischemic stroke using the Penumbra 5MAX ACE aspiration
      catheter on an intention to treat basis between November 2013 and June 2014.
      Procedural data, including modified Thrombolysis in Cerebral Infarction (mTICI)
      score, procedural timings, and complications, as well as clinical data at
      admission and discharge, were analyzed. RESULTS: 54 patients received mechanical
      thrombectomy using the 5MAX ACE. Median age was 69 (39-94) years (54% were men).
      Baseline National Institutes of Health Stroke Scale (NIHSS) score was 15 (2-27)
      and 44/54 (81%) patients received intravenous thrombolysis. Vessel occlusion
      sites were 91% anterior circulation and 9% posterior circulation. A successful
      revascularization result (mTICI >=2b) was achieved in 93% of cases whereas direct
      aspiration alone was successful in 30/54 (56%) cases; among these, median time
      from groin puncture to revascularization was 30 min (9-113). Symptomatic
      intracranial hemorrhage occurred in 2/54 (4%) patients, and embolization to new
      territories in 3/54 (6%). Median NIHSS at discharge was 6 (0-24); 46% of patients
      were independent at discharge. CONCLUSIONS: The direct aspiration first pass
      technique proofed to be fast, effective, and safe. Promising revascularization
      results can be achieved quickly in more than 50% of patients using this technique
      as the firstline option. Nevertheless, stent retrievers are still warranted in
      approximately 40% of cases to achieve a favorable revascularization result.

PMID- 25583534
TI  - Relative CBV ratio on perfusion-weighted MRI indicates the probability of early
      recanalization after IV t-PA administration for acute ischemic stroke.
AB  - BACKGROUND: We hypothesized that the relative cerebral blood volume (rCBV) ratio
      on perfusion-weighted imaging (PWI) using MRI might serve as a predictor of early
      recanalization (ER) after intravenous tissue plasminogen activator (IV t-PA)
      administration for acute ischemic stroke. METHODS: Patients with acute middle
      cerebral artery (MCA) ischemic stroke (IS) were enrolled in the study. They were
      evaluated by MRI, including PWI and diffusion-weighted imaging, before
      administration of IV t-PA and underwent digital subtraction angiography (DSA) of
      the brain within 2 h after t-PA administration. We compared the rCBV ratio on PWI
      between patients with and without ER on DSA and investigated the proportion of
      patients with an excellent outcome at 90 days after t-PA administration (modified
      Rankin Scale score 0-1) among those with and without ER. RESULTS: 85 patients
      with acute MCA IS were included; 16 patients (18.8%) experienced ER on DSA after
      IV t-PA administration. Patients with ER more frequently had an excellent outcome
      at 90 days than those without ER. The rCBV ratio on PWI was higher in the ER
      group (1.01+/-0.21, p<0.01) than in the non-ER group (0.82+/-0.18). After
      adjusting for the presence of atrial fibrillation and the serum glucose level,
      the rCBV ratio on PWI (OR 1.07; 95% CI 1.02 to 1.12; p<0.01) was a significant
      independent indicator of ER. CONCLUSIONS: The results of this study suggest that
      the rCBV ratio on PWI might serve as a useful indicator of ER after IV t-PA
      administration.

PMID- 25583535
TI  - Translating cardiovascular knowledge: a global health perspective.

PMID- 25583536
TI  - Evaluation of ethical aspects in health technology assessment: more methods than
      applications?
AB  - Health technology assessment (HTA) emerged with the increased need for
      systematical evaluation of health technologies in the 1970s. From its very
      beginning, ethics was a constitutive part of HTA, and over the years a wide range
      of approaches have been suggested to address ethical aspects of health
      technologies. Despite a vast variety of methodologies in ethics, there is no
      consensus about the appropriateness of the existing methods. Moreover, while the
      available methods are many, their applications are few. While methods for
      addressing ethical issues in HTA have been richly reviewed, their applications
      are poorly tracked. Hence, a bottom up approach, that is, from practice to
      theory, may turn out to be as helpful as a top-down review. We need a review of
      the examples of ethics in HTA so we better can learn how the methods are used in
      practice, analyze the role of context, and better can assess the merits of the
      various methods. 

PMID- 25583537
TI  - Does assessing the value for money of therapeutic medical devices require a
      flexible approach?
AB  - Regulation criteria for licensing pharmaceuticals and medical devices (MDs) are
      asymmetric. This has affected the type, quantity and quality of the evidence
      produced in support of MDs. This paper has three objectives: to examine the
      reasons behind the current licensing criteria for MDs; to identify key
      methodological challenges associated with pre- and post-market evaluation of MDs
      and to assess the extent to which existing methods for the economic evaluation of
      pharmaceuticals can be applied to the evaluation of MDs. The belief that MDs
      cannot be properly evaluated stems from a combination of historical events and
      complexities in implementing rigorous RCTs in this field. Existing challenges to
      conduct sound economic evaluation of MDs have begun to be addressed in medical
      research using mixed research methods. While more challenging to implement,
      robust evaluations of therapeutic MDs can and need to be carried out to safeguard
      individual's wellbeing. 

PMID- 25583538
TI  - Anagostic interactions under pressure: attractive or repulsive?
AB  - Square-planar d(8)-ML4 complexes might display subtle but noticeable local Lewis
      acidic sites in axial direction in the valence shell of the metal atom. These
      sites of local charge depletion provide the electronic prerequisites to establish
      weakly attractive 3c-2e M???H-C agostic interactions, in contrast to earlier
      assumptions. Furthermore, we show that the use of the sign of the (1)H NMR shifts
      as major criterion to classify M???H-C interactions as attractive (agostic) or
      repulsive (anagostic) can be dubious. We therefore suggest a new characterization
      method to probe the response of these M???H-C interactions under pressure by
      combined high pressure IR and diffraction studies.

PMID- 25583539
TI  - Large pore mesoporous silica nanomaterials for application in delivery of
      biomolecules.
AB  - Various approaches for the synthesis of mesoporous silicate nanoparticles (MSN)
      with large pore (LP) diameters (in the range of 3-50 nm) are reviewed in this
      article. The work also covers the construction of magnetic analogues of large
      pore-mesoporous silica nanoparticles (LPMMSN) and their biomedical applications.
      The constructed materials exhibit vast potential for application in the loading
      and delivery of large drug molecules and biomolecules. Literature reports on the
      application of LPMSN and LPMMSN materials for the adsorption and delivery of
      proteins, enzymes, antibodies, and nucleic acids are covered in depth, which
      exemplify their highly potent characteristics for use in drug and biomolecule
      delivery to diseased tissues. 

PMID- 25583540
TI  - Advances in the synthesis and application of nanoparticles for drug delivery.
AB  - The continuous development of drug delivery systems (DDSs) has been extensively
      researched by the need to maximize therapeutic efficacy while minimizing
      undesirable side effects. Nanoparticle technology was recently shown to hold
      great promise for drug delivery applications in nanomedicine due to its
      beneficial properties, such as better encapsulation, bioavailability, control
      release, and lower toxic effect. Despite the great progress in nanomedicine,
      there remain many limitations for clinical application. To overcome these
      limitations, advanced nanoparticles for drug delivery have been developed to
      enable the spatially and temporally controlled release of drugs in response to
      specific stimuli at disease sites. Furthermore, the controlled self-assembly of
      organic and inorganic materials may enable their use in theranostic applications.
      This review presents an overview of a recent advanced nanoparticulate system that
      can be used as a potential drug delivery carrier and focuses on the potential
      applications of nanoparticles in various biomedical fields for human health care.

PMID- 25583542
TI  - Protocols for the measurement of the F2-isoprostane, 15(S)-8-iso-prostaglandin
      F2alpha, in biological samples by GC-MS or GC-MS/MS coupled with immunoaffinity
      column chromatography.
AB  - Arachidonic acid, the origin of the eicosanoids family, occurs in biological
      samples as free acid and as ester in lipids. Free arachidonic acid is oxidized to
      numerous metabolites by means of enzymes including cyclooxygenase (COX).
      Arachidonic acid esterified to lipids is attacked by reactive oxygen species
      (ROS) to generate numerous oxidized arachidonic acid derivatives. Generally, it
      is assumed that ROS-derived arachidonic acid derivatives are distinct from those
      generated by enzymes such as COX. Therefore, ROS-generated eicosanoids are
      considered specific biomarkers of oxidative stress. However, there are serious
      doubts concerning a strict distinction between the enzyme-derived eicosanoids and
      the ROS-derived iso-eicosanoids. Prominent examples are prostaglandin F2alpha
      (PGF2alpha) and 15(S)-8-iso-prostaglandin F2alpha (15(S)-8-iso-PGF2alpha) which
      have been originally considered to exclusively derive from COX and ROS,
      respectively. There is convincing evidence that both COX and ROS can oxidize
      arachidonic acid to PGF2alpha and 15(S)-8-iso-PGF2alpha. Thus, many results
      previously reported for 15(S)-8-iso-PGF2alpha as exclusive ROS-dependent reaction
      product, and consequently as a specific biomarker of oxidative stress, require a
      careful re-examination which should also consider the analytical methods used to
      measure 15(S)-8-iso-PGF2alpha. This prominent but certainly not the only example
      underlines more than ever the importance of the analytical chemistry in basic and
      clinical research areas of oxidative stress. In the present work, we report
      analytical protocols for the reliable quantitative determination of 15(S)-8-iso
      PGF2alpha in human biological samples including plasma and urine by mass
      spectrometry coupled to gas chromatography (GC-MS, GC-MS/MS) after specific
      isolation of endogenous 15(S)-8-iso-PGF2alpha and the externally added internal
      standard [3,3',4,4'-(2)H4]-15(S)-8-iso-PGF2alpha by immunoaffinity column
      chromatography (IAC). 15(S)-8-iso-PGF2alpha esterified to plasma lipids is
      hydrolysed by KOH. 15(S)-8-iso-PGF2alpha and [3,3',4,4'-(2)H4]-15(S)-8-iso
      PGF2alpha are analyzed as pentafluorobenzyl ester trimethylsilyl ether
      derivatives in the electron-capture negative-ion chemical ionization mode.

PMID- 25583543
TI  - A -819 C/T polymorphism in the interleukin-10 promoter is associated with
      persistent HBV infection, but -1082 A/G and -592A/C polymorphisms are not: a meta
      analysis.
AB  - Single-nucleotide polymorphisms (SNPs) in the interleukin-10 (IL10) gene promoter
      have been associated with persistent hepatitis B virus (HBV) infection. In
      particular, the -1082A/G, -819 C/T and -592 A/C polymorphisms have most often
      been implicated. We performed a meta-analysis of available data to determine the
      relative importance of these SNPs in persistent HBV infection. We searched
      available articles in NCBI PubMed, EMBASE, the Chinese National Knowledge
      Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM) and
      identified 24 studies for inclusion in our meta-analysis. Our results indicated
      that the presence of the IL10 -819 C allele significantly increased the risk for
      persistent HBV infection (CC+CT vs. TT: OR = 1.283, 95 % CI 1.023-1.610, P =
      0.031; C vs. T: OR = 1.183, 95 % CI 1.001-1.399, P = 0.049). Meanwhile, the 
      1082A/-819T/-592A haplotype (OR = 0.751, 95 % CI 0.640-0.881, P = 0.000) and the 
      1082A/-819C/-592C haplotype (OR = 1.568, 95 % CI 1.304-1.884, P = 0.000) were
      observed to be significantly associated with HBV disease progression in Asians.
      In contrast, the IL10 -1082A/G and -592A/C polymorphisms were not associated with
      an increased susceptibility to or outcome of HBV infection. Our meta-analysis
      supports the growing body of evidence that the presence of the IL10 -819 C/T
      polymorphism is associated with persistent HBV infection and that the -1082A/
      819T/-592A haplotype and the -1082A/-819C/-592C haplotype are associated with HBV
      disease progression in Asians.

PMID- 25583541
TI  - Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred
      approach. Update to a position statement of the American Diabetes Association and
      the European Association for the Study of Diabetes.

PMID- 25583544
TI  - Mannose receptor mediated phagocytosis of bacteria in macrophages of blunt snout
      bream (Megalobrama amblycephala) in a Ca(2+)-dependent manner.
AB  - Mannose receptor (MR) is an important pattern-recognition receptor in macrophages
      and plays a critical role in immune responses. It is has been reported that
      mammalian macrophages are able to engulf a wide range of microorganisms mediated
      by Ca(2+)-dependent MR binding to terminal mannose residues which are frequently
      found on the pathogen surfaces. However, little is known about the MR-mediated
      phagocytosis in macrophages of fish. In this report, the distributions of MR in
      the macrophage and head kidney tissue from blunt snout bream were examined using
      MaMR specific antibody generated in our lab. Mannan and MaMR specific antibody
      inhibition experiments results collectively showed that MR was involved in the
      GFP-expressed E. coli engulfed in the macrophages, resulting in respiratory
      burst, nitric oxide production as well as inflammatory cytokines secretion, and
      the MaMR-mediated phagocytosis was Ca(2+)-dependent. These results will shed a
      new light on the immune functions of teleost MRs. 

PMID- 25583545
TI  - Four crustins involved in antibacterial responses in Marsupenaeus japonicus.
AB  - Crustins are a family of cationic, cysteine-rich antimicrobial peptides with a
      whey acidic protein (WAP) domain in the C-terminal. They have diverse functions
      in antimicrobial immune responses. Four groups of crustins (crustins I, II, III,
      and IV) have been identified in crustaceans, but type I crustins have not been
      reported in penaeid shrimp until now. In this study, we identified four crustins
      in kuruma shrimp Marsupenaeus japonicus, and named them MjCrus I-2, 3, 4 and 5.
      These four crustins belong to type I crustins, which contain a signal peptide,
      cysteine-rich region at the N-terminus, and WAP domain at the C-terminus. Tissue
      distribution demonstrated that MjCrus I-2, 3 and 5 had high expression levels in
      hemocytes, gills and stomach. whereas MjCrus I-4 was distributed in all tissues
      detected. MjCrus I-2 to 5 showed different expression patterns in different
      tissues after Gram-positive bacterial (Staphylococcus aureus), Gram-negative
      bacterial (Vibrio anguillarum), and white spot syndrome virus (WSSV) challenge.
      The expression of MjCrus I-2 to 5 was upregulated by bacterial or WSSV challenge.
      The three crustins were recombinantly expressed in Escherichia coli, and the
      purified proteins showed few antimicrobial activities. Three MjCrus Is could bind
      to different bacteria. MjCrus I-2 and 3 showed different inhibitory abilities to
      secreted bacterial proteases. MjCrus I-4 could not inhibit bacterial proteases.
      After knockdown of MjCrus I-3, the bacterial scavenging ability to V. anguillarum
      was impaired. These results suggested that type I crustins played an important
      role in the innate immunity of shrimp. 

PMID- 25583546
TI  - Leptin promotes dentin sialophosphoprotein expression in human dental pulp.
AB  - INTRODUCTION: Leptin, an inflammation-related adipokine, and its receptor (LEPR)
      are expressed in human dental pulp. Dentin sialophosphoprotein (DSPP) is involved
      in dentinogenesis and the dental pulp reparative response. The cell type
      expressing LEPR in dental human pulp and the resultant effect of the binding of
      leptin to LEPR remain unknown. This study describes the immmunohistochemical
      localization of LEPR and the effect of leptin on DSPP expression in human dental
      pulp. METHODS: Twenty-five dental pulp specimens were obtained from freshly
      extracted caries-free and restoration-free human third molars. LEPR localization
      was examined by immunohistochemistry using the antihuman LEPR monoclonal
      antibody. The effect of leptin on DSPP expression was determined by immunoblot
      analysis and quantitative real-time polymerase chain reaction. RESULTS:
      Immunoreactivity for LEPR concentrated in the odontoblast layer but was not
      evident in the central zone of the dental pulp. Leptin dose dependently
      stimulated DSPP expression. Western blot analysis revealed the presence of a
      protein with an apparent molecular weight of ~00 kDa, the estimated molecular
      weight of DSPP. The expression of DSPP messenger RNA was confirmed by
      quantitative real-time polymerase chain reaction, and the size of the amplified
      fragments (298 bp) was confirmed by agarose gel electrophoresis. CONCLUSIONS: The
      present study shows that human dental pulp is immunoreactive for LEPR, with the
      immunoreactivity concentrated in the odontoblast layer, and that leptin
      stimulates, in a dose-dependent manner, DSPP protein and messenger RNA (mRNA)
      expression in human dental pulp. These findings further support the functional
      role of leptin in the dentin mineralization process and/or in dental pulp
      reparative and immune responses.

PMID- 25583547
TI  - Expression and function of the actin-severing protein adseverin in the
      proliferation, migration, and differentiation of dental pulp cells.
AB  - INTRODUCTION: Adseverin is an actin-severing and actin-capping protein that is
      primarily expressed in secretory cells, where it regulates the filamentous actin
      cytoskeleton during cell differentiation and exocytosis. However, little is known
      regarding its regulatory role in dental pulp cells (DPCs). This study examined
      the expression and function of adseverin in the proliferation, migration, and
      odontoblastic differentiation of DPCs. METHODS: DPCs were assayed for morphologic
      changes, proliferation, migration, alkaline phosphatase activity, and dentin
      sialoprotein and dentin matrix protein-1 protein levels in vitro after knockdown
      of adseverin by using small interfering RNA. Tooth germs isolated from Sprague
      Dawley rats were processed for immunohistochemistry analysis of adseverin.
      RESULTS: Adseverin expression was increased in a time-dependent fashion in the
      early stage of odontoblastic differentiation. When adseverin expression was
      suppressed in DPCs, their cellular morphology was altered, and their
      proliferation, migration, and odontoblastic differentiation were substantially
      decreased in vitro. Secretory odontoblasts in the tooth germ at day 5 post partum
      expressed a stronger adseverin signal compared with those at days 1 and 3 post
      partum. CONCLUSIONS: Adseverin may play a crucial role in the proliferation,
      migration, and odontoblastic differentiation of DPCs via filamentous actin
      cytoskeleton regulation. However, further investigations are required to clarify
      the underlying mechanisms.

PMID- 25583548
TI  - Coexistence of ferromagnetism and superconductivity in iron based pnictides: a
      time resolved magnetooptical study.
AB  - Ferromagnetism and superconductivity are antagonistic phenomena. Their
      coexistence implies either a modulated ferromagnetic order parameter on a
      lengthscale shorter than the superconducting coherence length or a weak exchange
      coupling between the itinerant superconducting electrons and the localized
      ordered spins. In some iron based pnictide superconductors the coexistence of
      ferromagnetism and superconductivity has been clearly demonstrated. The nature of
      the coexistence, however, remains elusive since no clear understanding of the
      spin structure in the superconducting state has been reached and the reports on
      the coupling strength are controversial. We show, by a direct optical pump-probe
      experiment, that the coupling is weak, since the transfer of the excess energy
      from the itinerant electrons to ordered localized spins is much slower than the
      electron-phonon relaxation, implying the coexistence without the short
      lengthscale ferromagnetic order parameter modulation. Remarkably, the
      polarization analysis of the coherently excited spin wave response points towards
      a simple ferromagnetic ordering of spins with two distinct types of ferromagnetic
      domains. 

PMID- 25583549
TI  - Update in cardiology: vascular risk and cardiac rehabilitation.
AB  - As in other fields, understanding of vascular risk and rehabilitation is
      constantly improving. The present review of recent epidemiological update shows
      how far we are from achieving good risk factor control: in diet and nutrition,
      where unhealthy and excessive societal consumption is clearly increasing the
      prevalence of obesity; in exercise, where it is difficult to find a balance
      between benefit and risk, despite systemization efforts; in smoking, where
      developments center on programs and policies, with the electronic cigarette
      seeming more like a problem than a solution; in lipids, where the transatlantic
      debate between guidelines is becoming a paradigm of the divergence of views in
      this extensively studied area; in hypertension, where a nonpharmacological
      alternative (renal denervation) has been undermined by the SYMPLICITY HTN-3
      setback, forcing a deep reassessment; in diabetes mellitus, where the new
      dipeptidyl peptidase-4 and sodium-glucose cotransporter type 2 inhibitors and
      glucagon like peptide 1 analogues have contributed much new information and a
      glimpse of the future of diabetes treatment, and in cardiac rehabilitation, which
      continues to benefit from new information and communication technologies and
      where clinical benefit is not hindered by advanced diseases, such as heart
      failure. Our summary concludes with the update in elderly patients, whose
      treatment criteria are extrapolated from those of younger patients, with the
      present review clearly indicating that should not be the case. 

PMID- 25583550
TI  - Maternal abuse history, postpartum depression, and parenting: links with
      preschoolers' internalizing problems.
AB  - The current study examined a temporal cascade linking mothers' history of abuse
      with their children's internalizing difficulties through proximal processes such
      as maternal postnatal depressive symptoms and responsive parenting. Participants
      consisted of 490 mother-child dyads assessed at three time points when children
      were, on average, 2 months old at Time 1 (T1), 18 months at Time 2 (T2), and 36
      months at Time 3 (T3). Maternal abuse history and depressive symptoms were
      assessed via questionnaires at T1. Observations of responsive parenting were
      collected at T2 and were coded using a validated coding scheme. Children's
      internalizing difficulties were assessed in the preschool period using averaged
      parental reports. Path analysis revealed that maternal physical abuse was
      associated with depressive symptoms postnatally, which were in turn associated
      with children's internalizing behavior at 36 months of age. We also found that
      the association between physical abuse history and responsive parenting operated
      indirectly through maternal depressive symptoms. These findings remained after
      controlling for covariates including socioeconomic status, child gender, and age.
      After accounting for physical abuse history, sexual abuse history was not
      associated with child internalizing problems either directly or indirectly
      through maternal depressive symptoms and/or parenting behavior. Thus, mothers'
      physical abuse history is a risk factor for relatively poor mental health, which
      is itself predictive of both later parenting behavior and children's
      internalizing problems. 

PMID- 25583551
TI  - An unusual presentation of a rare benign tumor in the head and neck: A review of
      hibernomas.
AB  - Hibernomas are rare benign tumors that may present in the head and neck in an
      unusual manner similar to more common malignant tumors such as lymphoma. Our case
      report describes several characteristics of a patient and benign tumor
      presentation that is atypical for the usual presentation of hibernomas as
      reviewed in the literature. Although hibernomas are rare, our report and review
      of the literature highlights a particular patient population and important key
      findings that should make one consider these benign tumors in the differential
      diagnosis of a young patient presenting with a neck mass.

PMID- 25583552
TI  - The neglected topic: presentation of cost information in patient decision AIDS.
AB  - Costs are an important component of patients' decision making, but a
      comparatively underemphasized aspect of formal shared decision making. We
      hypothesized that decision aids also avoid discussion of costs, despite their
      being tools designed to facilitate shared decision making about patient-centered
      outcomes. We sought to define the frequency of cost-related information and
      identify the common modes of presenting cost and cost-related information in the
      290 decision aids catalogued in the Ottawa Hospital Research Institute's Decision
      Aid Library Inventory (DALI) system. We found that 56% (n = 161) of the decision
      aids mentioned cost in some way, but only 13% (n = 37) gave a specific price or
      range of prices. We identified 9 different ways in which cost was mentioned. The
      most common approach was as a "pro" of one of the treatment options (e.g., "you
      avoid the cost of medication"). Of the 37 decision aids that gave specific prices
      or ranges of prices for treatment options, only 2 were about surgery decisions
      despite the fact that surgery decision aids were the most common. Our findings
      suggest that presentation of cost information in decision aids is highly
      variable. Evidence-based guidelines should be developed by the International
      Patient Decision Aid Standards (IPDAS) Collaboration.

PMID- 25583553
TI  - Consequences of crown shortening canine teeth in Greenland sled dogs.
AB  - OBJECTIVES: To evaluate the consequences of crown shortening, focusing on the
      prevalence of pulp exposure and periapical pathology in Greenland sled dogs that
      had had their canine crowns shortened at an early age. METHODS: Five cadaver
      heads and 54 sled dogs underwent an oral examination for dental fractures and
      pulp exposure of canines. All canines were radiographed and evaluated for
      periapical pathology. RESULTS: The prevalence of canine pulp exposure in 12 (5
      heads and 7 dogs) crown shortened dogs was 91 . 7%, and 21 . 3% in 47 not-crown
      shortened dogs. A significant (P < 0 . 001) risk of pulp exposure of the canines
      in the crown shortened group compared to the not-crown shortened group was seen
      with a relative risk of 4 . 3 on a dog basis and a relative risk of 12 . 2 on a
      tooth basis. In dogs with pulp exposure of canines (n = 51) the prevalence of
      periapical pathology was 82 . 4%, but only 0 . 8% in dogs without pulp exposure
      (n = 133) resulting in a significant (relative risk, 109 . 5; P < 0 . 001) risk
      of periapical pathology in teeth with pulp exposure compared to teeth without
      pulp exposure. CLINICAL SIGNIFICANCE: The high risk of periapical pathology
      observed in teeth with pulp exposure confirms that these teeth should not be
      neglected in affected dogs.

PMID- 25583554
TI  - Quasi-particle energies and optical excitations of hydrogenated and fluorinated
      germanene.
AB  - Using density functional theory, the G0W0 method and Bethe-Salpeter equation
      calculations, we systematically explore the structural, electronic and optical
      properties of hydrogenated and fluorinated germanene. The
      hydrogenated/fluorinated germanene tends to form chair and zigzag-line
      configurations and its electronic and optical properties show close geometry
      dependence. The chair hydrogenated/fluorinated and zigzag-line fluorinated
      germanene are direct band-gap semiconductors, while the zigzag-line hydrogenated
      germanene owns an indirect band-gap. Moreover, the quasi-particle corrections are
      significant and strong excitonic effects with large exciton binding energies are
      observed. Moreover, the zigzag-line hydrogenated/fluorinated germanene shows
      highly anisotropic optical responses, which may be used as a good optical linear
      polarizer. 

PMID- 25583555
TI  - The current status and prospects of antibody engineering for therapeutic use:
      focus on glycoengineering technology.
AB  - Monoclonal antibodies have demonstrated enormous potential as new classes of
      drugs that confer great benefits to patients, and more than 40 therapeutic
      antibodies have already been approved for clinical use. In particular, the past 5
      years might be recognized as the period guiding the new era for "engineered
      antibodies," with the successful approval of numerous antibody-drug conjugates,
      bispecific antibodies, and glyco-engineered antibodies for clinical applications.
      In this review, we summarize the development of antibody engineering technologies
      that are proving their concepts in the clinic, mainly focusing on the latest
      trends in defucosylated antibody technologies.

PMID- 25583556
TI  - Nonfearful Panic Attacks in Patients With Noncardiac Chest Pain.
AB  - OBJECTIVE: To document the prevalence and characteristics of nonfearful panic
      attacks (NFPA) and their consequences on panic identification and access to
      mental health services in patients with noncardiac chest pain. METHOD: This cross
      sectional sample included 339 patients with noncardiac chest pain and panic
      attacks. A structured interview was used to collect data on panic attacks,
      psychiatric morbidity, sociodemographic variables, and previous consultations
      with a psychiatrist or psychologist. Medical files were reviewed to assess the
      rate of NFPA identification in the emergency department. RESULTS: In our sample
      of patients with noncardiac chest pain, 39% of those with panic attacks reported
      NFPA. Psychiatric morbidity was lower in patients with NFPA than in patients with
      typical panic attacks (49.6% vs 71.1%), as was the mean number of panic symptoms
      (6 vs 7.8). The rate of panic attack identification was similar in both the
      groups, but patients with NFPA were less likely to have consulted a psychiatrist
      or psychologist during their lifetime (34% vs 46%). CONCLUSIONS: NFPA were highly
      prevalent in our sample of emergency department patients with noncardiac chest
      pain. NFPA is associated with significant psychiatric morbidity but these
      patients were less likely to follow through with referral to a psychiatrist or
      psychologist than patients with typical panic attacks were.

PMID- 25583557
TI  - Therapy for recurrent bleeding from rectal varices by EUS-guided sclerosis.

PMID- 25583559
TI  - A single-molecular twin rotor: correlated motion of two pyrimidine rings
      coordinated to copper.
AB  - We describe the two correlated rotational motions of pyrimidine rings in 4,4'
      dimethyl-2,2'-bipyrimidine ligated to Cu(i). The two pyrimidine rings delimited
      by anthryl and phenanthroline groups rotate to afford three isomers. (1)H NMR
      measurements revealed that the two rotational processes were activated at
      different temperatures. Cyclic voltammetry gave the kinetic and thermodynamic
      parameters that provide clear evidence of the correlation between the two
      rotational steps. 

PMID- 25583558
TI  - Detection rates of premalignant polyps during screening colonoscopy: time to
      revise quality standards?
AB  - BACKGROUND: Standards for the detection of adenomas during screening colonoscopy
      are widely used to measure examination quality. No such standards exist for
      sessile serrated adenomas (SSAs). OBJECTIVE: To measure both the adenoma
      detection rate (ADR) and SSA detection rate (SSADR) during screening colonoscopy
      before and after quality improvement/financial incentive measures. DESIGN:
      Retrospective determination of baseline ADR/SSADR by the endoscopist, followed by
      prospective collection of data after informing physicians of baseline detection
      rates. SETTING: Tertiary cancer center with a large cancer screening program.
      PATIENTS: A total of 2833 average-risk colorectal cancer screening patients 50 to
      75 years of age undergoing initial colonoscopy. DATA COLLECTION: Electronic
      medical records for indication and demographics, endoscopy report, and pathology
      report. MAIN OUTCOME MEASUREMENTS: Detection rates of adenomas and SSAs by sex.
      RESULTS: The overall ADR in male and female patients was 50.6% and 36.6%,
      respectively. The overall detection rate of advanced adenomas in male and female
      patients was 12.4% and 6.5%, respectively. The overall SSADR in male and female
      patients was 10.1% and 7.1%, respectively. In 108 patients (3.8% of entire
      group), SSAs were the only premalignant lesions found. Detection rates of both
      types of premalignant polyps improved over time but did not reach statistical
      significance. LIMITATIONS: Single-center experience with limited sample size and
      small group of endoscopists. CONCLUSION: ADRs far in excess of current standards
      are achievable. Cecal withdrawal time is associated with the ADR. Prevalence of
      SSA rivals that of advanced adenomas and is greater than current medical
      literature suggests. The combination of monitoring and financial incentives did
      not result in statistically significant improvement in ADRs.

PMID- 25583560
TI  - Thermogenesis in white adipose tissue: An unfinished story about PPARgamma.
AB  - BACKGROUND: Recruiting thermogenic adipocytes in white adipose tissue represents
      a potential therapeutic strategy for obesity. Interestingly, PPARgamma, a major
      regulator of lipogenesis, is also a key factor in inducing thermogenic genes in
      adipose tissue. SCOPE OF THE REVIEW: We summarize some of the recent findings
      regarding the biology of beige adipocytes and their potential significance for
      metabolic health. We also discuss the role of PPARgamma in development of beige
      adipocyte phenotype and in inducing two apparently divergent processes, namely,
      lipogenesis and thermogenesis. MAJOR CONCLUSIONS: PPARgamma post-translation
      modifications and differential coregulator recruitment may be key factors in
      defining adipocyte commitment with lipogenesis or thermogenesis. GENERAL
      SIGNIFICANCE: Dissecting the mechanisms underlying its thermogenic effects may
      prompt the development of a new generation of PPARgamma-based therapies.

PMID- 25583561
TI  - Ziploc-ing the structure: Triple helix formation is coordinated by rough
      endoplasmic reticulum resident PPIases.
AB  - BACKGROUND: Protein folding is crucial for proteins' specific functions and is
      facilitated by various types of enzymes and molecular chaperones. The peptidyl
      prolyl cis/trans isomerases (PPIase) are one of these families of enzymes. They
      ubiquitously exist inside the cell and there are eight PPIases in the rough
      endoplasmic reticulum (rER), a compartment where the folding of most secreted
      proteins occurs. SCOPE OF REVIEW: We review the functional and structural aspects
      of individual rER resident PPIases. Furthermore, we specifically discuss the role
      of these PPIases during collagen biosynthesis, since collagen is the most
      abundant protein in humans, is synthesized in the rER, and contains a
      proportionally high number of proline residues. MAJOR CONCLUSIONS: The rER
      resident PPIases recognize different sets of substrates and facilitate their
      folding. Although they are clearly catalysts for protein folding, they also have
      more broad and multifaceted functions. We propose that PPIases coordinate
      collagen biosynthesis in the rER. GENERAL SIGNIFICANCE: This review expands our
      understanding of collagen biosynthesis by explaining the influence of novel
      indirect mechanisms of regulating folding and this is also explored for PPIases.
      We also suggest future directions of research to obtain a better understanding of
      collagen biosynthesis and functions of PPIases in the rER. This article is part
      of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts
      and Drug Targets.

PMID- 25583563
TI  - Measuring inhibitory processes for alcohol-related attentional biases:
      introducing a novel attentional bias measure.
AB  - INTRODUCTION: Attentional biases for alcohol related information (AB) have often
      been reported for heavy drinkers. These attentional biases have been found to
      have predictive value regarding relapse in abstaining alcoholics. Similarly
      impaired inhibitory processes have also been found to be associated with heavy
      drinkers. This paper describes a new experimental paradigm that can be utilised
      to investigate attentional bias towards alcohol-related visual stimuli,
      specifically the ability to inhibit the orientation of initial and sustained
      attention, towards peripherally appearing stimuli. In this way we hope to study a
      novel aspect of attentional biases and how they relate to substance abuse.
      METHODS: We used a novel eye-tracking task which aims to measure inhibitory
      processes for AB. The experiment utilised a gaze contingency paradigm to measure
      the compulsion to process or attend to alcohol stimuli. 86 undergraduate
      participants were recruited (31 males; 55 females), aged 18-49 years (m = 20.88;
      sd = 4.52). A 'break frequency' variable was computed for each participant. This
      was the number of times that participants tried to look at peripheral stimuli. We
      argue that this variable is a direct measure of how distracting peripheral
      stimuli were. RESULTS: It was found that reported alcohol use was associated with
      the eye-tracking break frequency measure of inhibitory control. Thus, heavy
      drinking may be associated with decreased inhibitory control and increased
      attentional bias. CONCLUSIONS: Results suggest that attentional bias is not just
      a process of stimuli becoming prioritised, but also stimuli becoming compulsory
      to attend and process.

PMID- 25583565
TI  - Planar holographic metasurfaces for terahertz focusing.
AB  - Scientists and laymen alike have always been fascinated by the ability of lenses
      and mirrors to control light. Now, with the advent of metamaterials and their two
      dimensional counterpart metasurfaces, such components can be miniaturized and
      designed with additional functionalities, holding promise for system integration.
      To demonstrate this potential, here ultrathin reflection metasurfaces (also
      called metamirrors) designed for focusing terahertz radiation into a single spot
      and four spaced spots are proposed and experimentally investigated at the
      frequency of 0.35 THz. Each metasurface is designed using a computer-generated
      spatial distribution of the reflection phase. The phase variation within 360 deg
      is achieved via a topological morphing of the metasurface pattern from metallic
      patches to U-shaped and split-ring resonator elements, whose spectral response is
      derived from full-wave electromagnetic simulations. The proposed approach
      demonstrates a high-performance solution for creating low-cost and lightweight
      beam-shaping and beam-focusing devices for the terahertz band. 

PMID- 25583562
TI  - Pin1 dysregulation helps to explain the inverse association between cancer and
      Alzheimer's disease.
AB  - BACKGROUND: Pin1 is an intracellular signaling molecule which plays a critical
      but opposite role in the pathogenesis of Alzheimer's disease (AD) and many human
      cancers. SCOPE OF REVIEW: We review the structure and function of the Pin1
      enzyme, the diverse roles it plays in cycling cells and neurons, the
      epidemiologic evidence for the inverse association between cancer and AD, and the
      potential therapeutic implications of Pin1-based therapies. MAJOR CONCLUSIONS:
      Pin1 is a unique enzyme that has effects on the function of target proteins by
      "twisting" them into different shapes. Cycling cells use Pin1 to help coordinate
      cell division. It is over-expressed and/or activated by multiple mechanisms in
      many common human cancers, and acts on multiple signal pathways to promote
      tumorigenesis. Inhibition of Pin1 in animal models has profound anti-tumor
      effects. In contrast, Pin1 is down-regulated or inactivated by multiple
      mechanisms in AD brains. The absence of Pin1 impairs tau function and amyloid
      precursor protein processing, leading to tangle- and amyloid-related pathologies
      and neurodegeneration in an age-dependent manner, resembling human AD. We have
      developed cis and trans conformation-specific antibodies to provide the first
      direct evidence that tau exists in distinct cis and trans conformations and that
      Pin1 accelerates its cis to trans conversion, thereby protecting against tangle
      formation in AD. GENERAL SIGNIFICANCE: Available studies on Pin1 suggest that
      cancer and AD may share biological pathways that are deregulated in different
      directions. Pin1 biology opens exciting preventive and therapeutic horizons for
      both cancer and neurodegeneration. This article is part of a Special Issue
      entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets.

PMID- 25583564
TI  - ALLMAPS: robust scaffold ordering based on multiple maps.
AB  - The ordering and orientation of genomic scaffolds to reconstruct chromosomes is
      an essential step during de novo genome assembly. Because this process utilizes
      various mapping techniques that each provides an independent line of evidence, a
      combination of multiple maps can improve the accuracy of the resulting
      chromosomal assemblies. We present ALLMAPS, a method capable of computing a
      scaffold ordering that maximizes colinearity across a collection of maps. ALLMAPS
      is robust against common mapping errors, and generates sequences that are
      maximally concordant with the input maps. ALLMAPS is a useful tool in building
      high-quality genome assemblies. ALLMAPS is available at:
      https://github.com/tanghaibao/jcvi/wiki/ALLMAPS . 

PMID- 25583566
TI  - EGFR tyrosine kinase inhibitors versus cranial radiation therapy for EGFR mutant
      non-small cell lung cancer with brain metastases: a systematic review and meta
      analysis.
AB  - BACKGROUND AND PURPOSE: EGFR TKIs alone have demonstrated activity against
      intracranial disease in EGFR mutant non-small cell lung cancer (NSCLC). This
      study aimed to determine if upfront cranial radiotherapy improves intracranial
      disease control and survival outcomes in EGFR mutant NSCLC with brain metastases
      relative to TKIs alone. MATERIALS AND METHODS: We searched MEDLINE and various
      conference proceedings from 2008 to July 2014 for eligible studies where patients
      received upfront cranial radiotherapy or TKIs alone. Outcomes of interest were
      overall intracranial disease response rate (ORR), four-month intracranial disease
      progression-free survival (PFS), two-year overall survival (OS) and neurological
      adverse events (AE). We used random effects models to pool outcomes across
      studies and compared them using interaction tests. RESULTS: We found 12 non
      comparative observational studies (n=363) with severe methodological limitations.
      Upfront cranial radiotherapy results in similar intracranial disease ORR
      (relative risk (RR) 0.93, 95% confidence interval (CI) 0.82-1.06; interaction p
      value (p)=0.53), improved four-month intracranial disease PFS (RR 1.06, 95% CI
      1.00-1.12; p=0.03), improved two-year OS (RR 1.33, 95% CI 1.00-1.77; p=0.05) but
      caused more neurological AEs than TKIs alone. CONCLUSION: There is evidence,
      albeit of low quality, that upfront cranial radiotherapy may improve intracranial
      disease control and survival outcomes compared with TKI alone.

PMID- 25583567
TI  - Survival and prognostic factors in 321 patients treated with stereotactic body
      radiotherapy for oligo-metastases.
AB  - BACKGROUND AND PURPOSE: To establish a model to predict survival after SBRT for
      oligo-metastases in patients considered ineligible for surgical resection (SR)
      and radiofrequency ablation (RFA). MATERIAL AND METHODS: Overall survival (OS)
      rates were estimated in 321 patients treated for 587 metastases with SBRT over
      13years. Patients were treated for a variety of metastasis types with colorectal
      cancer (CRC) being the most frequent (n=201). RESULTS: With a median follow-up
      time of 5.0years, the median OS was 2.4years (95% CI 2.3-2.7) and the survival
      rates were 80%, 39%, 23% and 12% at 1, 3, 5 and 7.5years after SBRT,
      respectively. WHO performance status (PS) (0-1) (HR 0.49; p<0.001), solitary
      metastasis (HR 0.75; p=0.049), metastasis ?30mm (HR 0.53; p<0.001), metachronous
      metastases (HR 0.71; p=0.02) and pre-SBRT chemotherapy (HR 0.59; p<0.001) were
      independently related to favorable OS. Median OS rates were 7.5, 2.8, 2.5, 1.7
      and 0.8years with 0, 1, 2, 3, ?4 unfavorable prognostic factors, respectively.
      The treatment-related morbidity was moderate. However, three deaths were possibly
      treatment-related. CONCLUSION: Prognostic factors may predict long-term survival
      in patients with oligo-metastases treated with SBRT.

PMID- 25583569
TI  - Regarding Edmunds et al. Cardiac volume effects during chemoradiotherapy for
      esophageal cancer.

PMID- 25583568
TI  - A multicentre 'end to end' dosimetry audit for cervix HDR brachytherapy
      treatment.
AB  - PURPOSE: To undertake the first multicentre fully 'end to end' dosimetry audit
      for HDR cervix brachytherapy, comparing planned and delivered dose distributions
      around clinical treatment applicators, with review of local procedures. MATERIALS
      AND METHODS: A film-dosimetry audit was performed at 46 centres, including
      imaging, applicator reconstruction, treatment planning and delivery. Film dose
      maps were calculated using triple-channel dosimetry and compared to RTDose data
      from treatment planning systems. Deviations between plan and measurement were
      quantified at prescription Point A and using gamma analysis. Local procedures
      were also discussed. RESULTS: The mean difference between planned and measured
      dose at Point A was -0.6% for plastic applicators and -3.0% for metal
      applicators, at standard uncertainty 3.0% (k=1). Isodose distributions agreed
      within 1mm over a dose range 2-16Gy. Mean gamma passing rates exceeded 97% for
      plastic and metal applicators at 3% (local) 2mm criteria. Two errors were found:
      one dose normalisation error and one applicator library misaligned with the
      imaged applicator. Suggestions for quality improvement were also made.
      CONCLUSIONS: The concept of 'end to end' dosimetry audit for HDR brachytherapy
      has been successfully implemented in a multicentre environment, providing
      evidence that a high level of accuracy in brachytherapy dosimetry can be
      achieved.

PMID- 25583570
TI  - Hormones and the bone marrow: panhypopituitarism and pancytopenia in a man with a
      pituitary adenoma.
AB  - In rare cases, pancytopenia results from hormonal deficiencies that arise in the
      setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old
      man who presented with progressive fatigue and polyuria, and whose laboratory
      workup revealed a deficiency of the five hormones associated with the action of
      the anterior pituitary (thyroid hormone, testosterone, cortisol, prolactin, and
      insulin-like growth factor-1). Imaging of the pituitary demonstrated a cystic
      mass consistent with a pituitary adenoma replacing much of the normal pituitary
      tissue. His symptoms and hematologic abnormalities rapidly resolved with
      prednisone and levothyroxine supplementation. While the majority of reported
      cases of panhypopituitarism with bone marrow suppression are the result of
      peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan's
      syndrome), it is also important to consider the diagnosis of hypopituitarism in
      patients with hypothyroidism, low cortisol levels, and pancytopenia. The causal
      relationship between pancytopenia and panhypopituitarism is not well understood,
      though it does reinforce the important influence of these endocrine hormones on
      the health of the bone marrow. 

PMID- 25583571
TI  - Impact of long-term meditation practice on cardiovascular reactivity during
      perception and reappraisal of affective images.
AB  - Meditation has been found to be an efficient strategy for coping with stress in
      healthy individuals and in patients with psychosomatic disorders. The main
      objective of the present study was to investigate the psychophysiological
      mechanisms of beneficial effects of meditation on cardiovascular reactivity. We
      examined effects of long-term Sahaja Yoga meditation on cardiovascular reactivity
      during affective image processing under "unregulated" and "emotion regulation"
      conditions. Twenty two experienced meditators and 20 control subjects
      participated in the study. Under "unregulated" conditions participants were shown
      neutral and affective images and were asked to attend to them. Under "emotion
      regulation" conditions they down-regulated negative affect through reappraisal of
      negative images or up-regulated positive affect through reappraisal of positive
      images. Under "unregulated" conditions while anticipating upcoming images
      meditators vs. controls did not show larger pre-stimulus total peripheral
      resistance and greater cardiac output for negative images in comparison with
      neutral and positive ones. Control subjects showed TPR decrease for negative
      images only when they consciously intended to reappraise them (i.e. in the
      "emotion regulation" condition). Both meditators and controls showed comparable
      cardiovascular reactivity during perception of positive stimuli, whereas up
      regulating of positive affect was associated with more pronounced cardiac
      activation in meditators. The findings provide some insight into understanding
      the beneficial influence of meditation on top-down control of emotion and
      cardiovascular reactivity. 

PMID- 25583572
TI  - Target-context unitization effect on the familiarity-related FN400: a face
      recognition exclusion task.
AB  - Using two exclusion tasks, the present study examined how the ERP correlates of
      face recognition are affected by the nature of the information to be retrieved.
      Intrinsic (facial expression) and extrinsic (background scene) visual information
      were paired with face identity and constituted the exclusion criterion at test
      time. Although perceptual information had to be taken into account in both
      situations, the FN400 old-new effect was observed only for old target faces on
      the expression-exclusion task, whereas it was found for both old target and old
      non-target faces in the background-exclusion situation. These results reveal that
      the FN400, which is generally interpreted as a correlate of familiarity, was
      modulated by the retrieval of intra-item and intrinsic face information, but not
      by the retrieval of extrinsic information. The observed effects on the FN400
      depended on the nature of the information to be retrieved and its relationship
      (unitization) to the recognition target. On the other hand, the parietal old-new
      effect (generally described as an ERP correlate of recollection) reflected the
      retrieval of both types of contextual features equivalently. The current findings
      are discussed in relation to recent controversies about the nature of the
      recognition processes reflected by the ERP correlates of face recognition. 

PMID- 25583574
TI  - What's in a name?

PMID- 25583573
TI  - The effects of unitization on the contribution of familiarity and recollection
      processes to associative recognition memory: evidence from event-related
      potentials.
AB  - Familiarity and recollection are two independent cognitive processes involved in
      recognition memory. It is traditionally believed that both familiarity and
      recollection can support item recognition, whereas only recollection can support
      associative recognition. Here, using a standard associative recognition task, we
      examined whether associative retrieval of unitized associations involved
      differential patterns of familiarity and recollection processes relative to non
      unitized associations. The extent of engagement of familiarity and recollection
      processes during associative retrieval was estimated by using event-related
      potentials (ERPs). Twenty participants studied compound words and unrelated word
      pairs during encoding. Subsequently, they were asked to decide whether a
      presented word pair was intact, rearranged, or a new pair while
      electroencephalogram (EEG) was recorded. ERP results showed that compound words
      evoked a significant early frontal old/new effect (associated with familiarity)
      between ERPs to intact and rearranged word pairs, whereas this effect disappeared
      for the unrelated word pairs. In addition, the left parietal old/new effect
      (associated with recollection) between ERPs to intact and rearranged word pairs
      was greater for compounds than for unrelated word pairs. These findings suggest
      that unitization enhances the contribution of both familiarity and recollection
      processes to associative recognition. 

PMID- 25583575
TI  - Isoflavones enhance interleukin-17 gene expression via retinoic acid receptor
      related orphan receptors alpha and gamma.
AB  - The retinoic acid receptor-related orphan receptors alpha and gamma (RORalpha and
      RORgamma), are key regulators of helper T (Th)17 cell differentiation, which is
      involved in the innate immune system and autoimmune disorders. In this study, we
      investigated the effects of isoflavones on RORalpha/gamma activity and the gene
      expression of interleukin (IL)-17, which mediates the function of Th17 cells. In
      doxycycline-inducible CHO stable cell lines, we found that four isoflavones,
      biochanin A (BA), genistein, formononetin, and daidzein, enhanced RORalpha- or
      RORgamma-mediated transcriptional activity in a dose-dependent manner. In an
      activation assay of the Il17a promoter using Jurkat cells, these compounds
      enhanced the RORalpha- or RORgamma-mediated activation of the Il17a promoter at
      concentrations of 1 * 10(-6)M to 1 * 10(-5)M. In mammalian two-hybrid assays, the
      four isoflavones enhanced the interaction between the RORalpha- or RORgamma
      ligand binding domain and the co-activator LXXLL peptide in a dose-dependent
      manner. In addition, these isoflavones potently enhanced Il17a mRNA expression in
      mouse T lymphoma EL4 cells treated with phorbol myristate acetate and ionomycin,
      but showed slight enhancement of Il17a gene expression in RORalpha/gamma
      knockdown EL4 cells. Immunoprecipitation and immunoblotting assays also revealed
      that BA enhanced the interaction between RORgammat and SRC-1, which is a co
      activator for nuclear receptors. Taken together, these results suggest that the
      isoflavones have the ability to enhance IL-17 gene expression by stabilizing the
      interactions between RORalpha/gamma and co-activators. This also provides the
      first evidence that dietary chemicals can enhance IL-17 gene expression in immune
      cells.

PMID- 25583576
TI  - Revisiting NMR composite pulses for broadband (2)H excitation.
AB  - Quadrupolar echo NMR spectroscopy of static solids often requires RF excitation
      that covers spectral widths exceeding 100 kHz, which is difficult to obtain due
      to instrumental limitations. In this work we revisit four well-known composite
      pulses (COM-I, II, III and IV) for broadband excitation in deuterium quadrupolar
      echo spectroscopy. These composite pulses are combined with several phase cycling
      schemes that were previously shown to decrease finite pulse width distortions in
      deuterium solid-echo experiments performed with two single pulses. The
      simulations and experiments show that COM-II and IV composite pulses combined
      with an 8-step phase cycling aid in achieving broadband excitation with limited
      pulse width distortions.

PMID- 25583577
TI  - NKG2D ligand overexpression in lupus nephritis correlates with increased NK cell
      activity and differentiation in kidneys but not in the periphery.
AB  - NK cells are a major component of the immune system, and alterations in their
      activity are correlated with various autoimmune diseases. In the present work, we
      observed an increased expression of the NKG2D ligand MICA in SLE patients'
      kidneys but not healthy subjects. We also show glomerulus-specific expression of
      the NKG2D ligands Rae-1 and Mult-1 in various murine SLE models, which correlated
      with a higher number of glomerular-infiltrating NK cells. As the role of NK cells
      in the immunopathogenesis of SLE is poorly understood, we explored NK cell
      differentiation and activity in tissues and organs in SLE-prone murine models by
      use of diseased and prediseased MRL/MpJ and MRL/lpr mice. We report here that
      phenotypically iNK cells accumulate only in the spleen but not in BM or kidneys
      of diseased mice. Infiltrating NK cells in kidneys undergoing a lupus nephritic
      process showed a more mature, activated phenotype compared with kidney, as well
      as peripheral NK cells from prediseased mice, as determined by IFN-gamma and
      STAT5 analysis. These findings and the presence of glomerulus-specific NKG2D
      ligands in lupus-prone mice identify a role for NK cells and NKG2D ligands in the
      lupus nephritic process, which could aid in understanding their role in human
      SLE. 

PMID- 25583579
TI  - Streptococcal M1 protein triggers chemokine formation, neutrophil infiltration,
      and lung injury in an NFAT-dependent manner.
AB  - Streptococcus pyogenes of the M1 serotype can cause STSS, which is associated
      with significant morbidity and mortality. The purpose of the present study was to
      examine the role of NFAT signaling in M1 protein-induced lung injury. NFAT-luc
      mice were treated with the NFAT inhibitor A-285222 before administration of the
      M1 protein. Neutrophil infiltration, edema, and CXC chemokines were quantified in
      the lung, 4 h after challenge with the M1 protein. Flow cytometry was used to
      determine Mac-1 expression. Challenge with the M1 protein increased NFAT
      dependent transcriptional activity in the lung, spleen, and liver in NFAT-luc
      mice. Administration of the NFAT inhibitor A-285222 abolished M1 protein-evoked
      NFAT activation in the lung, spleen, and liver. M1 protein challenge induced
      neutrophil recruitment, edema, and CXC chemokine production in the lung, as well
      as up-regulation of Mac-1 on circulating neutrophils. Inhibition of NFAT activity
      attenuated M1 protein-induced neutrophil infiltration by 77% and edema formation
      by 50% in the lung. Moreover, administration of A-285222 reduced M1 protein
      evoked pulmonary formation of CXC chemokine >80%. In addition, NFAT inhibition
      decreased M1 protein-triggered Mac-1 up-regulation on neutrophils. These findings
      indicate that NFAT signaling controls pulmonary infiltration of neutrophils in
      response to streptococcal M1 protein via formation of CXC chemokines and
      neutrophil expression of Mac-1. Thus, the targeting of NFAT activity might be a
      useful way to ameliorate lung injury in streptococcal infections. 

PMID- 25583578
TI  - Myeloid-derived suppressor cells regulate T cell and B cell responses during
      autoimmune disease.
AB  - MDSCs are a heterogeneous group of myeloid cells that suppress T cell activity in
      cancer and autoimmune disease. The effect of MDSCs on B cell function is not
      clear. Using the CIA model of autoimmune disease, we found an increase in M-MDSCs
      in the periphery of WT mice with CIA compared with naive mice. These MDSCs were
      absent from the periphery of CCR2(-/-) mice that developed exacerbated disease. M
      MDSCs, isolated from immunized mice, inhibited autologous CD4(+) T cell
      proliferation. The M-MDSC-mediated suppression of T cell proliferation was NO and
      IFN-gamma dependent but IL-17 independent. Furthermore, we demonstrated for the
      first time that M-MDSCs from CIA mice also inhibited autologous B cell
      proliferation and antibody production. The suppression of B cells by M-MDSCs was
      dependent on the production of NO and PGE2 and required cell-cell contact.
      Administration of M-MDSCs rescued CCR2(-/-) mice from the exacerbated CIA
      phenotype and ameliorated disease in WT mice. Furthermore, adoptive transfer of M
      MDSCs reduced autoantibody production by CCR2(-/-) and WT mice. In summary, M
      MDSCs inhibit T cell and B cell function in CIA and may serve as a therapeutic
      approach in the treatment of autoimmune arthritis. 

PMID- 25583580
TI  - In- and outdoor reproduction of first generation common sole Solea solea under a
      natural photothermal regime: Temporal progression of sexual maturation assessed
      by monitoring plasma steroids and gonadotropin mRNA expression.
AB  - Reproduction of many temperate fishes is seasonal and maturation and spawning of
      gametes are under photothermal control. Reproductive success of first generation
      (G1) common sole Solea solea in captivity has been low. In this study, the sexual
      maturation status has been assessed during the prespawning months in G1 sole that
      were housed (a) outdoor under the natural photoperiod and temperature, or (b)
      indoor under artificial photothermal induction. Maturation was assessed in male
      and female G1 broodstock in November as controls, after which the remaining
      population was divided over two outdoor flow-through tanks placed in a pond and
      two indoor recirculating aquaculture system (RAS) tanks. Subsequently, maturation
      status (gonadosomatic index GSI and plasma levels of testosterone T and 17beta
      estradiol E2) was assessed in one tank for each condition in January, February
      and during spawning in early April, while fish in the other tank were not
      disturbed in achieving reproductive success. Quantitative real-time PCR was
      performed to determine species-specific gonadotropin mRNA expression in females.
      Successful G1 spawning and egg fertilisation occurred in all experimental tanks.
      Gonadal development was similar under both conditions. Higher E2 and T levels
      were found in indoor housed females. Gonadotropin expression revealed similar
      profiles between outdoor and indoor housed females. G1 sole could be reproduced
      in the outdoor tanks under the natural photoperiod and in the indoor tanks under
      artificial simulation of this regime that includes a potentially crucial chilling
      period of 2-3 months at 5-7  degrees C.

PMID- 25583581
TI  - Production of reproductively sterile fish: A mini-review of germ cell elimination
      technologies.
AB  - As seafood consumption shifts from fisheries harvests to artificially propagated
      aquatic species, the increase of aquaculture activities poses a biological threat
      to our environment. Selectively bred, non-native and (eventually) genetically
      engineered farmed fish may escape from aquaculture operations, propagate and/or
      interbreed with wild stocks and subsequently alter the genetic makeup of
      populations in the environment. Thus, an effective strategy for bio-containment
      of farmed fish is critically needed. Farming reproductively sterile fish is the
      most environmentally sustainable approach to ensure complete bio-containment in
      large-scale aquaculture operations. Chromosome set manipulations to produce
      sterile fish, including polyploidy and hybridization, are currently the most
      common practices in the aquaculture industry. However, they do not always result
      in 100% sterility of the treated fish. Moreover, triploid fish typically do not
      perform as well as the non-manipulated diploids under commercial culture
      conditions. In the last half decade, several genetic engineering methods have
      been developed to produce sterile fish. In this review, we will address the
      latest technologies that use transgenic approaches to eliminate germ cells,
      resulting in the production of sterile fish. These latest advances also led us to
      the development of egg/embryo immersion methodologies to deliver and screen
      compounds that can be used to eliminate primordial germ cells and produce sterile
      fish. This emerging non-transgenic strategy for the production of reproductively
      sterile fish in aquaculture will also be discussed. 

PMID- 25583582
TI  - Influence of temperature on thyroid hormone signaling and endocrine disruptor
      action in Rana (Lithobates) catesbeiana tadpoles.
AB  - Thyroid hormones (THs) are essential for normal growth, development, and
      metabolic control in vertebrates. Their absolute requirement during amphibian
      metamorphosis provides a powerful means to detect and assess the impact of
      environmental contaminants on TH signaling in the field and laboratory. As
      poikilotherms, frogs can experience considerable temperature fluctuations.
      Previous work demonstrated that low temperature prevents precocious TH-dependent
      induction of metamorphosis. However, a shift to a permissive higher temperature
      allows resumption of the induced metamorphic program regardless of whether or not
      TH remains. We investigated the impact of temperature on the TH-induced gene
      expression programs of premetamorphic Rana (Lithobates) catesbeiana tadpoles
      following a single injection of 10pmol/g body wet weight 3,3',5-triiodothyronine
      (T3). Abundance profiles of several T3-responsive mRNAs in liver, brain, lung,
      back skin, and tail fin were characterized under permissive (24 degrees C),
      nonpermissive (5 degrees C), or temperature shift (5-24 degrees C) conditions.
      While responsiveness to T3 was retained to varying degrees at nonpermissive
      temperature, T3 modulation of thibz occurred in all tissues at 5 degrees C
      suggesting an important role for this transcription factor in initiation of T3
      dependent gene expression programs. Low temperature immersion of tadpoles in
      water containing 10nM T3 and the nonsteroidal anti-inflammatory drug, ibuprofen,
      or the antimicrobial agent, triclosan, perturbed some aspects of the gene
      expression programs of tail fin and back skin that was only evident upon
      temperature shift. Such temporal uncoupling of chemical exposure and resultant
      biological effects in developing frogs necessitates a careful evaluation of
      environmental temperature influence in environmental monitoring programs. 

PMID- 25583583
TI  - Novel associations between contaminant body burdens and biomarkers of
      reproductive condition in male Common Carp along multiple gradients of
      contaminant exposure in Lake Mead National Recreation Area, USA.
AB  - Adult male Common Carp were sampled in 2007/08 over a full reproductive cycle at
      Lake Mead National Recreation Area. Sites sampled included a stream dominated by
      treated wastewater effluent, a lake basin receiving the streamflow, an upstream
      lake basin (reference), and a site below Hoover Dam. Individual body burdens for
      252 contaminants were measured, and biological variables assessed included
      physiological [plasma vitellogenin (VTG), estradiol-17beta (E2), 11
      ketotestosterone (11KT)] and organ [gonadosomatic index (GSI)] endpoints.
      Patterns in contaminant composition and biological condition were determined by
      Principal Component Analysis, and their associations modeled by Principal
      Component Regression. Three spatially distinct but temporally stable gradients of
      contaminant distribution were recognized: a contaminant mixture typical of
      wastewaters (PBDEs, methyl triclosan, galaxolide), PCBs, and DDTs. Two
      spatiotemporally variable patterns of biological condition were recognized: a
      primary pattern consisting of reproductive condition variables (11KT, E2, GSI),
      and a secondary pattern including general condition traits (condition factor,
      hematocrit, fork length). VTG was low in all fish, indicating low estrogenic
      activity of water at all sites. Wastewater contaminants associated negatively
      with GSI, 11KT and E2; PCBs associated negatively with GSI and 11KT; and DDTs
      associated positively with GSI and 11KT. Regression of GSI on sex steroids
      revealed a novel, nonlinear association between these variables. Inclusion of sex
      steroids in the GSI regression on contaminants rendered wastewater contaminants
      nonsignificant in the model and reduced the influence of PCBs and DDTs. Thus, the
      influence of contaminants on GSI may have been partially driven by organismal
      modes-of-action that include changes in sex steroid production. The positive
      association of DDTs with 11KT and GSI suggests that lifetime, sub-lethal
      exposures to DDTs have effects on male carp opposite of those reported by studies
      where exposure concentrations were relatively high. Lastly, this study
      highlighted advantages of multivariate/multiple regression approaches for
      exploring associations between complex contaminant mixtures and gradients and
      reproductive condition in wild fishes. 

PMID- 25583584
TI  - Regulation of the avian central melanocortin system and the role of leptin.
AB  - The avian central melanocortin system is well conserved between birds and mammals
      in terms of the component genes, the localisation of their expression in the
      hypothalamic arcuate nucleus, the effects on feeding behaviour of their encoded
      peptides and the sensitivity of agouti-related protein (AGRP) and pro
      opiomelanocortin (POMC) gene expression to changes in energy status. Our recent
      research has demonstrated that AGRP gene expression precisely differentiates
      between broiler breeder hens with different histories of chronic food restriction
      and refeeding. We have also shown that the sensitivity of AGRP gene expression to
      loss of energy stores is maintained even when food intake has been voluntarily
      reduced in chickens during incubation and in response to a stressor. However, the
      similarity between birds and mammals does not appear to extend to the way AGRP
      and POMC gene expression are regulated. In particular, the preliminary evidence
      from the discovery of the first avian leptin (LEP) genes suggests that LEP is
      more pleiotropic in birds and may not even be involved in regulating energy
      balance. Similarly, ghrelin exerts inhibitory, rather than stimulatory, effects
      on food intake. The fact that the importance of these prominent long-term
      regulators of AGRP and POMC expression in mammals appears diminished in birds
      suggests that the balance of regulatory inputs in birds may have shifted to more
      short-term influences such as the tone of cholecystokinin (CCK) signalling. This
      is likely to be related to the different metabolic fuelling required to support
      flight. 

PMID- 25583585
TI  - Effect of estradiol on apoptosis, proliferation and steroidogenic enzymes in the
      testes of the toad Rhinella arenarum (Amphibia, Anura).
AB  - Estrogens inhibit androgen production and this negative action on amphibian
      steroidogenesis could be related to the regulation of steroidogenic enzymes.
      Estrogens are also involved in the regulation of amphibian spermatogenesis by
      controlling testicular apoptosis and spermatogonial proliferation. The Bidder's
      organ (BO) is a structure characteristic from the Bufonidae family and in adult
      males of Rhinella arenarum it is one of the main sources of plasma estradiol
      (E2). The purpose of this study is to analyze the effect of E2 on testicular
      steroidogenic enzymes, apoptosis and proliferation in the toad R. arenarum. For
      this purpose, testicular fragments were treated during 24h with or without 2 or
      20nM of E2. After treatments, the activities of cytochrome P450 17alpha
      hydroxylase-C17-20 lyase (CypP450c17) and 3beta-hydroxysteroid
      dehydrogenase/isomerase (3beta-HSD/I) were measured by the transformation of
      radioactive substrates into products, and CypP450c17 expression was determined by
      Western blot analysis. Apoptosis in testicular sections was detected with a
      commercial fluorescent kit based on TUNEL method, and proliferation was evaluated
      by BrdU incorporation. Results indicate that E2 has no effect on CypP450c17
      protein levels or enzymatic activity, while it reduces 3beta-HSD/I activity
      during the post reproductive season. Furthermore, although E2 has no effect on
      apoptosis during the pre and the post reproductive seasons, it stimulates
      testicular apoptosis during the reproductive season, mostly in spermatocytes.
      Finally, E2 has no effect on testicular proliferation all year long. Taken
      together, these results suggest that E2 is involved in the regulation of
      testicular steroidogenesis and spermatogenesis. 

PMID- 25583586
TI  - The "Pathological Gambling and Epidemiology" (PAGE) study program: design and
      fieldwork.
AB  - The German federal states initiated the "Pathological Gambling and Epidemiology"
      (PAGE) program to evaluate the public health relevance of pathological gambling.
      The aim of PAGE was to estimate the prevalence of pathological gambling and cover
      the heterogenic presentation in the population with respect to comorbid substance
      use and mental disorders, risk and protective factors, course aspects, treatment
      utilization, triggering and maintenance factors of remission, and biological
      markers. This paper describes the methodological details of the study and reports
      basic prevalence data. Two sampling frames (landline and mobile telephone
      numbers) were used to generate a random sample from the general population
      consisting of 15,023 individuals (ages 14 to 64) completing a telephone
      interview. Additionally, high-risk populations have been approached in gambling
      locations, via media announcements, outpatient addiction services, debt
      counselors, probation assistants, self-help groups and specialized inpatient
      treatment facilities. The assessment included two steps: (1) a diagnostic
      interview comprising the gambling section of the Composite International
      Diagnostic Interview (CIDI) for case finding; (2) an in-depth clinical interview
      with participants reporting gambling problems. The in-depth clinical interview
      was completed by 594 participants, who were recruited from the general or high
      risk populations. The program provides a rich epidemiological database which is
      available as a scientific use file.

PMID- 25583587
TI  - [Comparative regions of interest study in schizophrenia, panic disorder and its
      comorbidity: the relationship between hippocampal volume and positive psychotic
      symptoms].
AB  - INTRODUCTION: Schizophrenia and panic disorder have been associated with limbic
      alterations, such as reduced volumes of the hippocampus and amygdala. However,
      there are conflicting results and a lack of previous neuroimaging studies
      assessing the implication of these structures when the two diagnosis are
      comorbid. AIM. To determine the type and magnitude of volumetric limbic
      alterations in schizophrenia, panic disorder and their comorbidity. SUBJECTS AND
      METHODS: We measured the volume of the amygdala and hippocampus using a manual
      regions of interest segmentation method in schizophrenic patients (group 1),
      panic disorder (group 2), those who present comorbidity of the two diagnosis
      (group 3), and a control group of healthy subjects (group 4). RESULTS: Patients
      included in groups 1 and 3 have significantly lower volume of left hippocampus
      than control group. In these groups, we did find that the volume of the left
      hippocampus was positively associated with positive symptoms' severity. We did
      not find volumetric differences in the amygdala between the groups. CONCLUSIONS:
      Our results confirm a decreased volume of the left hippocampus in schizophrenia.
      The association between the severity of positive psychotic symptoms (delusions
      and hallucinations) and hippocampus volume could be mediated by the propensity to
      develop a fear conditioned response to neutral stimuli in subjects with higher
      hippocampal volumes.

PMID- 25583588
TI  - [Effects of a programme of aquatic Ai Chi exercise in patients with fibromyalgia.
      A pilot study].
AB  - INTRODUCTION: Fibromyalgia is rheumathological disease a combination of physical,
      psychological and social limitations. The aim of the present study is to
      determinate the benefits of Ai Chi program on quality of life, depression and
      pain. PATIENTS AND METHODS: An experimental study was performed with 20
      fibromyalgia patients two different cities. Outcome measures were functional
      capacity (Fibromyalgia Impact Questionnaire), pain (Visual Analogue Scale) and
      quality of life (Short Form-36). Measures were performed at baseline and after
      ten weeks post-intervention. RESULTS: After ten weeks of treatment, the results
      showed significant reduction (p < 0,05) in virtually all outcome measures.
      CONCLUSION: An Ai Chi aquatic therapy programme contributes to reduce pain and
      improve quality of life as well as physical and mental health in patients with
      fibromyalgia.

PMID- 25583589
TI  - Creation and design of a test for the Evaluation of Upper Limb Apraxia (EULA)
      based on a cognitive model: a pilot study.
AB  - INTRODUCTION: Apraxia is regarded as neurological disorder characterized by a
      loss of ability to execute and carry out skilled movements and gestures despite
      intact motor and sensory systems, coordination, and comprehension. As reflected
      in the specialized literature, there are currently few tests that provide a
      global evaluation of this syndrome. This research created and designed a test for
      the Evaluation of Upper Limb Apraxia (EULA), based on theoretical models of
      apraxia. SUBJECTS AND METHODS: A sample of 57 patients was selected with
      subjective cognitive manifestations (complaints of cognitive impairment) and 39
      subjects without cognitive impairment. Both groups were given the EULA test as
      well as other tests. The structure of the EULA was verified with principal
      components factor analysis, and the reliability and validity of this instrument
      were also calculated. RESULTS: The factor analysis classified all of the items in
      the test in nine factors with an explained total variance of 69.91%. The high
      reliability of the test was reflected in a Cronbach's alpha of 0.929 and a
      Guttman split-half coefficient of 0.870. The construct validity was also
      satisfactory as shown in the significant correlation of six of the nine factors
      in the test with two other well-known apraxia subtests. CONCLUSIONS: The healthy
      subjects had a higher test score than the subjects with complaints of cognitive
      impairment, which confirmed the reliability and construct validity of the EULA.

PMID- 25583591
TI  - [Changes introduced into the recent International Classification of Headache
      Disorders: ICHD-III beta classification].
AB  - INTRODUCTION: The International Headache Society (IHS) has published the third
      edition of the International Classification of Headache Disorders (ICHD-III
      beta), the most commonly used guide to diagnosing headaches in the world. AIMS:
      To review the recent additions to the guide, to explain the new entities that
      appear in it and to compare the conditions that have had their criteria further
      clarified against the criteria in the previous edition. DEVELOPMENT: We have
      recorded a large number of clarifications in the criteria in practically all the
      headaches and neuralgias in the classification, but the conditions that have
      undergone the most significant clarifications are chronic migraine, primary
      headache associated with sexual activity, short-lasting unilateral neuralgiform
      headache attacks, new daily persistent headache, medication-overuse headache,
      syndrome of transient headache and neurological deficits with cerebrospinal fluid
      lymphocytosis. The most notable new entities that have been incorporated are
      external-compression headache, cold-stimulus headache, nummular headache,
      headache attributed to aeroplane travel and headache attributed to autonomic
      dysreflexia. Another point to be highlighted is the case of the new headaches
      (still not considered entities in their own right) included in the appendix, some
      of the most noteworthy being epicrania fugax, vestibular migraine and infantile
      colic. CONCLUSIONS: The IHS recommends no longer using the previous
      classification and changing over to the new classification (ICHD-III beta) in
      healthcare, teaching and research, in addition to making this new guide as widely
      known as possible.

PMID- 25583590
TI  - [Reversible neuropsychological deterioration associated to zonisamide in a
      paediatric patient with tuberous sclerosis].
AB  - AIM: To document reversible cognitive deterioration associated to high doses of
      zonisamide, using the Reliable Change Index to control practice effects derived
      from repetitive neuropsychological assessments. CASE REPORT: A 11 year-old boy
      with tuberous sclerosis complex and left frontal refractory epilepsy, evaluated
      within a paediatric epilepsy surgery program. The epileptogenic zone was found to
      be related with a tuber situated on the left inferior frontal gyrus. The effects
      of high doses of zonisamide simulate a disturbance of eloquent cortex within the
      epileptogenic zone and the impact of uncontrolled seizures on cognitive
      functioning over the language-dominant hemisphere. Drug withdrawal significantly
      improved total intelligence index, verbal comprehension intellectual index and
      specific language-sustained cognitive abilities, beyond practice effects.
      CONCLUSIONS: The differentiation between cognitive effects of drugs and
      functional deficits resulting from eloquent cortex involvement within the
      epileptogenic zone can be of crucial importance in the decision-making process
      for epilepsy surgery.

PMID- 25583592
TI  - [Anton's syndrome due to occipital necrosis after methanol poisoning].

PMID- 25583593
TI  - [Therapeutic response to pyridoxine and pyridostigmine in a paediatric case of
      severe peripheral and cranial polyneuropathy due to vincristine].

PMID- 25583594
TI  - [Fabry disease from the neurologist's point of view: is it a rare cause of
      strokes?].

PMID- 25583595
TI  - [First-time seizure in the emergency department].

PMID- 25583596
TI  - Age-Related Differences in Plausibility-Checking Strategies During Arithmetic
      Problem Verification Tasks.
AB  - OBJECTIVES: We examined whether older adults use plausibility-checking strategies
      while verifying arithmetic problems. We also tested trial-to-trial modulations of
      plausibility-checking strategies, and aging effects on these sequential
      modulations. METHOD: We asked young and older adults to verify arithmetic
      problems that violated or respected arithmetic rules (i.e., 5*16 = 87.
      True/False?). RESULTS: Both young and older adults solved problems violating
      parity rule and five rule more quickly than problems violating no rule. We also
      found that both age groups had better performance when both five rule and parity
      rule are violated than when only one or no rules are violated. These results
      suggest age invariance in using rule-violation checking strategies and a smaller,
      but still efficient, strategy combination in older adults. Finally, for young
      adults only, strategy combination was larger following problems violating rules
      than after problems respecting rules. DISCUSSION: These findings have important
      implications regarding mechanisms underlying age-related differences in using
      rule-violation checking strategies to verify arithmetic problems and in combining
      two strategies into a single, more efficient one.

PMID- 25583600
TI  - Edge reconstruction-mediated graphene fracture.
AB  - Creation of free edges in graphene during mechanical fracture is a process that
      is important from both fundamental and technological points of view. Here we
      derive an analytical expression for the energy of a free-standing reconstructed
      chiral graphene edge, with chiral angle varying from 0 degrees  to 30 degrees ,
      and test it by first-principles computations. We then study the thermodynamics
      and kinetics of fracture and show that during graphene fracture under uniaxial
      load it is possible to obtain fully reconstructed zigzag edges through sequential
      reconstructions at the crack tip. The preferable condition for this process is
      high temperature (T ~ 1000 K) and low (quasi-static) mechanical load (KI ~ 5.0 eV
      A(-5/2)). Edge configurations of graphene nanoribbons may be tuned according to
      these guidelines. 

PMID- 25583597
TI  - Social Relationships, Gender, and Recovery From Mobility Limitation Among Older
      Americans.
AB  - OBJECTIVES: Evidence suggests social relationships may be important facilitators
      for recovery from functional impairment, but the extant literature is limited in
      its measurement of social relationships including an over emphasis on filial
      social support and a paucity of nationally representative data. METHODS: Using
      data from Waves 4-9 (1998-2008) of the Health and Retirement Study (HRS), this
      research examines the association between social relationships and recovery from
      severe mobility limitation (i.e., difficulty walking one block or across the
      room) among older Americans. Using a more nuanced measure of recovery that
      includes complete and partial recovery, a series of discrete-time event history
      models with multiple competing recovery outcomes were estimated using multinomial
      logistic regression. RESULTS: Providing instrumental support to peers increased
      the odds of complete and partial recovery from severe mobility limitation, net of
      numerous social, and health factors. Having relatives living nearby decreased the
      odds of complete recovery, while being engaged in one's neighborhood increased
      the odds of partial recovery. The influence of partner status on partial and
      complete recovery varied by gender, whereby partnered men were more likely to
      experience recovery relative to partnered women. The effect of neighborhood
      engagement on partial recovery also varied by gender. Disengaged women were the
      least likely to experience partial recovery compared with any other group.
      DISCUSSION: The rehabilitative potential of social relationships has important
      policy implications. Interventions aimed at encouraging older adults with
      mobility limitation to be engaged in their neighborhoods and/or provide
      instrumental support to peers may improve functional health outcomes.

PMID- 25583599
TI  - Scalable template synthesis of resorcinol-formaldehyde/graphene oxide composite
      aerogels with tunable densities and mechanical properties.
AB  - Resorcinol-formaldehyde (RF) and graphene oxide (GO) aerogels have found a
      variety of applications owing to their excellent properties and remarkable
      flexibility. However, the macroscopic and controllable synthesis of their
      composite gels is still a great challenge. By using GO sheets as template
      skeletons and metal ions (Co(2+), Ni(2+), or Ca(2+)) as catalysts and linkers,
      the first low-temperature scalable strategy for the synthesis of a new kind of RF
      GO composite gel with tunable densities and mechanical properties was developed.
      The aerogels can tolerate a strain as high as 80% and quickly recover their
      original morphology after the compression has been released. Owing to their high
      compressibility, the gels might find applications in various areas, for example,
      as adsorbents for the removal of dye pollutants and in oil-spill cleanup.

PMID- 25583598
TI  - Personality and Cognitive Decline in Older Adults: Data From a Longitudinal
      Sample and Meta-Analysis.
AB  - OBJECTIVES: Personality traits are associated with risk of dementia; less is
      known about their association with the trajectory of cognitive functioning. This
      research examines the association between the 5 major dimensions of personality
      and cognitive function and decline in older adulthood and includes a meta
      analysis of published studies. METHOD: Personality traits, objective and
      subjective memory, and cognitive status were collected in a large national sample
      (N = 13,987) with a 4-year follow-up period. For each trait, the meta-analysis
      pooled results from up to 5 prospective studies to examine personality and change
      in global cognition. RESULTS: Higher Neuroticism was associated with worse
      performance on all cognitive measures and greater decline in memory, whereas
      higher Conscientiousness and Openness were associated with better memory
      performance concurrently and less decline over time. All traits were associated
      with subjective memory. Higher Conscientiousness and lower Extraversion were
      associated with better cognitive status and less decline. Although modest, these
      associations were generally larger than that of hypertension, diabetes, history
      of psychological treatment, obesity, smoking, and physical inactivity. The meta
      analysis supported the association between Neuroticism and Conscientiousness and
      cognitive decline. DISCUSSION: Personality is associated with cognitive decline
      in older adults, with effects comparable to established clinical and lifestyle
      risk factors.

PMID- 25583601
TI  - Genotoxicity of mesoporous silica nanoparticles in human embryonic kidney 293
      cells.
AB  - Mesoporous silica nanoparticles (MSNs) have been widely evaluated for their
      potential use as carriers for cancer diagnosis and therapy. Understanding the
      toxicity of MSNs is crucial to their biomedical applications. Although several
      groups have reported the cytotoxicity of MSNs, the genotoxicity (inducing genetic
      aberrations) of MSNs in normal human cells has not been extensively investigated.
      Gene amplification and mutation may initiate and promote carcinogenesis, and
      changes in mRNA expression can affect normal human physical functions. In this
      study, human embryonic kidney 293 (HEK293) cells were treated overnight with MSNs
      at a concentration of 120 ug/mL. The cells were assayed with fluorescent in situ
      hybridization to check for chromosome changes and gene amplification. Mutations
      in the epidermal growth factor receptor 1 (EGFR1) and KRAS genes were checked
      with DNA sequencing. The effects of MSNs on mRNA expression were investigated
      with an Agilent human mRNA microarray. No chromosomal alterations or gene
      mutations in EGFR or KRAS were observed in the control HEK293 cells or HEK293
      cells exposed to MSNs. The microarray analysis showed that MSNs significantly
      altered gene expression. The expression of 579 genes was upregulated and that of
      1263 genes was downregulated in HEK293 cells treated with MSNs compared with the
      control HEK293 cells. Our findings suggest that exposure to MSNs is genotoxic to
      normal human cells, leading to changes in the expression of some genes. This
      genotoxicity may cause cellular dysfunction and certain benign diseases. We have
      not shown that MSN exposure induces serious genotoxicity involving
      carcinogenesis.

PMID- 25583603
TI  - Prediction of protein structural class using tri-gram probabilities of position
      specific scoring matrix and recursive feature elimination.
AB  - Knowledge of structural class plays an important role in understanding protein
      folding patterns. As a transitional stage in recognition of three-dimensional
      structure of a protein, protein structural class prediction is considered to be
      an important and challenging task. In this study, we firstly introduce a feature
      extraction technique which is based on tri-grams computed directly from position
      specific scoring matrix (PSSM). A total of 8,000 features are extracted to
      represent a protein. Then, support vector machine-recursive feature elimination
      (SVM-RFE) is applied for feature selection and reduced features are input to a
      support vector machine (SVM) classifier to predict structural class of a given
      protein. To examine the effectiveness of our method, jackknife tests are
      performed on six widely used benchmark datasets, i.e., Z277, Z498, 1189, 25PDB,
      D640, and D1185. The overall accuracies of 97.1, 98.6, 92.5, 93.5, 94.2, and
      95.9% are achieved on these datasets, respectively. Comparison of the proposed
      method with other prediction methods shows that our method is very promising to
      perform the prediction of protein structural class.

PMID- 25583604
TI  - A direct method for the synthesis of orthogonally protected furyl- and thienyl-
      amino acids.
AB  - The synthesis of unnatural amino acids plays a key part in expanding the
      potential application of peptide-based drugs and in the total synthesis of
      peptide natural products. Herein, we report a direct method for the synthesis of
      orthogonally protected 5-membered heteroaromatic amino acids. 

PMID- 25583602
TI  - RIP1 modulates death receptor mediated apoptosis and autophagy in macrophages.
AB  - Macrophages are responsible for defending against diverse pathogens and play a
      crucial role in the innate immune system. Macrophage's lifespan is determined by
      homeostatic balance between survival and apoptosis. Here we report that tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers both apoptosis
      and autophagy in human U937 cells. Inhibition of autophagy facilitates TRAIL
      induced apoptosis, suggesting that autophagy of macrophages protects against
      TRAIL-induced apoptosis. TRAIL treatment influences the expression of death
      receptors, indicating that TRAIL-induced apoptosis and autophagy are mediated by
      death receptors. RIP1 ubiquitination and expression regulate apoptosis and
      autophagy. Furthermore, expression and bioactivity of the p43/41-caspase-8
      variant are critical to TRAIL-induced autophagy and apoptosis. Knockdown of RIP1
      suppresses autophagy in macrophage. These data demonstrate that RIP1 is essential
      for the regulation of death receptor mediated autophagy and apoptosis. The
      results in this study contribute to understanding the regulation of autophagy and
      apoptosis in macrophages, and shed lights on death receptor-targeted therapy for
      cancer, inflammation and autoimmune diseases. 

PMID- 25583606
TI  - Regional cerebellar volumes are related to early musical training and finger
      tapping performance.
AB  - The cerebellum has been associated with timing on the millisecond scale and with
      musical rhythm and beat processing. Early musical training (before age 7) is
      associated with enhanced rhythm synchronization performance and differences in
      cortical motor areas and the corpus callosum. In the present study, we examined
      the relationships between regional cerebellar volumes, early musical training,
      and timing performance. We tested adult musicians and non-musicians on a standard
      finger tapping task, and extracted cerebellar gray and white matter volumes using
      a novel multi-atlas automatic segmentation pipeline. We found that early-trained
      musicians had reduced volume in bilateral cerebellar white matter and right
      lobules IV, V and VI, compared to late-trained musicians. Strikingly, better
      timing performance, greater musical experience and an earlier age of start of
      musical training were associated with smaller cerebellar volumes. Better timing
      performance was specifically associated with smaller volumes of right lobule VI.
      Collectively, these findings support the sensitivity of the cerebellum to the age
      of initiation of musical training and suggest that lobule VI plays a role in
      timing. The smaller cerebellar volumes associated with musical training and
      timing performance may be a reflection of more efficiently implemented low-level
      timing and sensorimotor processes. 

PMID- 25583605
TI  - Dark-induced senescence of barley leaves involves activation of plastid
      transglutaminases.
AB  - Transglutaminases (E.C. 2.3.2.13) catalyze the post-translational modification of
      proteins by establishing epsilon-(gamma-glutamyl) lysine isopeptide bonds and by
      the covalent conjugation of polyamines to endo-glutamyl residues of proteins. In
      light of the confirmed role of transglutaminases in animal cell apoptosis and
      only limited information on the role of these enzymes in plant senescence, we
      decided to investigate the activity of chloroplast transglutaminases (ChlTGases)
      and the fate of chloroplast-associated polyamines in Hordeum vulgare L. 'Nagrad'
      leaves, where the senescence process was induced by darkness (day 0) and
      continued until chloroplast degradation (day 12). Using an anti-TGase antibody,
      we detected on a subcellular level, the ChlTGases that were associated with
      destacked/degraded thylakoid membranes, and beginning on day 5, were also found
      in the stroma. Colorimetric and radiometric assays revealed during senescence an
      increase in ChlTGases enzymatic activity. The MS/MS identification of plastid
      proteins conjugated with exogenous polyamines had shown that the ChlTGases are
      engaged in the post-translational modification of proteins involved in
      photosystem organization, stress response, and oxidation processes. We also
      computationally identified the cDNA of Hv-Png1-like, a barley homologue of the
      Arabidopsis AtPng1 gene. Its mRNA level was raised from days 3 to 10, indicating
      that transcriptional regulation controls the activity of barley ChlTGases.
      Together, the presented results deepen our knowledge of the mechanisms of the
      events happened in dark-induced senescence of barley leaves that might be
      activation of plastid transglutaminases. 

PMID- 25583607
TI  - Relationship of gamma-aminobutyric acid and glutamate+glutamine concentrations in
      the perigenual anterior cingulate cortex with performance of Cambridge Gambling
      Task.
AB  - The anterior cingulate cortex (ACC), consisting of the perigenual ACC (pgACC) and
      mid-ACC (i.e., affective and cognitive areas, respectively), plays a significant
      role in the performance of gambling tasks, which are used to measure decision
      making behavior under conditions of risk. Although recent neuroimaging studies
      have suggested that the gamma-aminobutyric acid (GABA) concentration in the pgACC
      is associated with decision-making behavior, knowledge regarding the relationship
      of GABA concentrations in subdivisions of the ACC with gambling task performance
      is still limited. The aim of our magnetic resonance spectroscopy study is to
      investigate in 20 healthy males the relationship of concentrations of GABA and
      glutamate+glutamine (Glx) in the pgACC, mid-ACC, and occipital cortex (OC) with
      multiple indexes of decision-making behavior under conditions of risk, using the
      Cambridge Gambling Task (CGT). The GABA/creatine (Cr) ratio in the pgACC
      negatively correlated with delay aversion score, which corresponds to the
      impulsivity index. The Glx/Cr ratio in the pgACC negatively correlated with risk
      adjustment score, which is reported to reflect the ability to change the amount
      of the bet depending on the probability of winning or losing. The scores of CGT
      did not significantly correlate with the GABA/Cr or Glx/Cr ratio in the mid-ACC
      or OC. Results of this study suggest that in the pgACC, but not in the mid-ACC or
      OC, GABA and Glx concentrations play a distinct role in regulating impulsiveness
      and risk probability during decision-making behavior under conditions of risk,
      respectively. 

PMID- 25583608
TI  - Patterns of neural activity in the human ventral premotor cortex reflect a whole
      body multisensory percept.
AB  - Previous research has shown that the integration of multisensory signals from the
      body in fronto-parietal association areas underlies the perception of a body part
      as belonging to one's physical self. What are the neural mechanisms that enable
      the perception of one's entire body as a unified entity? In one behavioral and
      one fMRI multivoxel pattern analysis experiment, we used a full-body illusion to
      investigate how congruent visuo-tactile signals from a single body part
      facilitate the emergence of the sense of ownership of the entire body. To elicit
      this illusion, participants viewed the body of a mannequin from the first-person
      perspective via head-mounted displays while synchronous touches were applied to
      the hand, abdomen, or leg of the bodies of the participant and the mannequin;
      asynchronous visuo-tactile stimuli served as controls. The psychometric data
      indicated that the participants perceived ownership of the entire artificial body
      regardless of the body segment that received the synchronous visuo-tactile
      stimuli. Based on multivoxel pattern analysis, we found that the neural responses
      in the left ventral premotor cortex displayed illusion-specific activity patterns
      that generalized across all tested pairs of body parts. Crucially, a tripartite
      generalization analysis revealed the whole-body specificity of these premotor
      activity patterns. Finally, we also identified multivoxel patterns in the
      premotor, intraparietal, and lateral occipital cortices and in the putamen that
      reflected multisensory responses specific to individual body parts. Based on
      these results, we propose that the dynamic formation of a whole-body percept may
      be mediated by neuronal populations in the ventral premotor cortex that contain
      visuo-tactile receptive fields encompassing multiple body segments. 

PMID- 25583610
TI  - Brain dynamics in the comprehension of action-related language. A time-frequency
      analysis of mu rhythms.
AB  - EEG mu rhythms (8-13 Hz) recorded at fronto-central electrodes are generally
      considered as markers of motor cortical activity in humans, because they are
      modulated when participants perform an action, when they observe another's action
      or even when they imagine performing an action. In this study, we analyzed the
      time-frequency (TF) modulation of mu rhythms while participants read action
      language ("You will cut the strawberry cake"), abstract language ("You will doubt
      the patient's argument"), and perceptive language ("You will notice the bright
      day"). The results indicated that mu suppression at fronto-central sites is
      associated with action language rather than with abstract or perceptive language.
      Also, the largest difference between conditions occurred quite late in the
      sentence, while reading the first noun, (contrast Action vs. Abstract), or the
      second noun following the action verb (contrast Action vs. Perceptive). This
      suggests that motor activation is associated with the integration of words across
      the sentence beyond the lexical processing of the action verb. Source
      reconstruction localized mu suppression associated with action sentences in
      premotor cortex (BA 6). The present study suggests (1) that the understanding of
      action language activates motor networks in the human brain, and (2) that this
      activation occurs online based on semantic integration across multiple words in
      the sentence.

PMID- 25583609
TI  - Analysis of the contribution of experimental bias, experimental noise, and inter
      subject biological variability on the assessment of developmental trajectories in
      diffusion MRI studies of the brain.
AB  - Metrics derived from the diffusion tensor, such as fractional anisotropy (FA) and
      mean diffusivity (MD) have been used in many studies of postnatal brain
      development. A common finding of previous studies is that these tensor-derived
      measures vary widely even in healthy populations. This variability can be due to
      inherent inter-individual biological differences as well as experimental noise.
      Moreover, when comparing different studies, additional variability can be
      introduced by different acquisition protocols. In this study we examined scans of
      61 individuals (aged 4-22 years) from the NIH MRI study of normal brain
      development. Two scans were collected with different protocols (low and high
      resolution). Our goal was to separate the contributions of biological variability
      and experimental noise to the overall measured variance, as well as to assess
      potential systematic effects related to the use of different protocols. We
      analyzed FA and MD in seventeen regions of interest. We found that biological
      variability for both FA and MD varies widely across brain regions; biological
      variability is highest for FA in the lateral part of the splenium and body of the
      corpus callosum along with the cingulum and the superior longitudinal fasciculus,
      and for MD in the optic radiations and the lateral part of the splenium. These
      regions with high inter-individual biological variability are the most likely
      candidates for assessing genetic and environmental effects in the developing
      brain. With respect to protocol-related effects, the lower resolution acquisition
      resulted in higher MD and lower FA values for the majority of regions compared
      with the higher resolution protocol. However, the majority of the regions did not
      show any age-protocol interaction, indicating similar trajectories were obtained
      irrespective of the protocol used.

PMID- 25583611
TI  - Acute modulation of the cholinergic system in the mouse brain detected by
      pharmacological resting-state functional MRI.
AB  - INTRODUCTION: The cholinergic system is involved in learning and memory and is
      affected in neurodegenerative disorders such as Alzheimer's disease. The
      possibility of non-invasively detecting alterations of neurotransmitter systems
      in the mouse brain would greatly improve early diagnosis and treatment
      strategies. The hypothesis of this study is that acute modulation of the
      cholinergic system might be reflected as altered functional connectivity (FC) and
      can be measured using pharmacological resting-state functional MRI (rsfMRI).
      MATERIAL AND METHODS: Pharmacological rsfMRI was performed on a 9.4T MRI scanner
      (Bruker BioSpec, Germany) using a gradient echo EPI sequence. All mice were
      sedated with medetomidine. C57BL/6 mice (N = 15/group) were injected with either
      saline, the cholinergic antagonist scopolamine, or methyl-scopolamine, after
      which rsfMRI was acquired. For an additional group (N = 8), rsfMRI scans of the
      same mouse were acquired first at baseline, then after the administration of
      scopolamine and finally after the additional injection of the cholinergic agonist
      milameline. Contextual memory was evaluated with the same setup as the
      pharmacological rsfMRI using the passive avoidance behavior test. RESULTS:
      Scopolamine induced a dose-dependent decrease of FC between brain regions
      involved in memory. Scopolamine-induced FC deficits could be recovered completely
      by milameline for FC between the hippocampus-thalamus, cingulate-retrosplenial,
      and visual-retrosplenial cortex. FC between the cingulate-rhinal, cingulate
      visual and visual-rhinal cortex could not be completely recovered by milameline.
      This is consistent with the behavioral outcome, where milameline only partially
      recovered scopolamine-induced contextual memory deficits. Methyl-scopolamine
      administered at the same dose as scopolamine did not affect FC in the brain.
      CONCLUSION: The results of the current study are important for future studies in
      mouse models of neurodegenerative disorders, where pharmacological rsfMRI may
      possibly be used as a non-invasive read-out tool to detect alterations of
      neurotransmitter systems induced by pathology or treatment.

PMID- 25583612
TI  - Attention enhances multi-voxel representation of novel objects in frontal,
      parietal and visual cortices.
AB  - Selective attention is fundamental for human activity, but the details of its
      neural implementation remain elusive. One influential theory, the adaptive coding
      hypothesis (Duncan, 2001, An adaptive coding model of neural function in
      prefrontal cortex, Nature Reviews Neuroscience 2:820-829), proposes that single
      neurons in certain frontal and parietal regions dynamically adjust their
      responses to selectively encode relevant information. This selective
      representation may in turn support selective processing in more specialized brain
      regions such as the visual cortices. Here, we use multi-voxel decoding of
      functional magnetic resonance images to demonstrate selective representation of
      attended--and not distractor--objects in frontal, parietal, and visual cortices.
      In addition, we highlight a critical role for task demands in determining which
      brain regions exhibit selective coding. Strikingly, representation of attended
      objects in frontoparietal cortex was highest under conditions of high perceptual
      demand, when stimuli were hard to perceive and coding in early visual cortex was
      weak. Coding in early visual cortex varied as a function of attention and
      perceptual demand, while coding in higher visual areas was sensitive to the
      allocation of attention but robust to changes in perceptual difficulty.
      Consistent with high-profile reports, peripherally presented objects could also
      be decoded from activity at the occipital pole, a region which corresponds to the
      fovea. Our results emphasize the flexibility of frontoparietal and visual
      systems. They support the hypothesis that attention enhances the multi-voxel
      representation of information in the brain, and suggest that the engagement of
      this attentional mechanism depends critically on current task demands.

PMID- 25583613
TI  - Bilateral dorsal and ventral fiber pathways for the processing of affective
      prosody identified by probabilistic fiber tracking.
AB  - Dorsal and ventral pathways for syntacto-semantic speech processing in the left
      hemisphere are represented in the dual-stream model of auditory processing. Here
      we report new findings for the right dorsal and ventral temporo-frontal pathway
      during processing of affectively intonated speech (i.e. affective prosody) in
      humans, together with several left hemispheric structural connections, partly
      resembling those for syntacto-semantic speech processing. We investigated white
      matter fiber connectivity between regions responding to affective prosody in
      several subregions of the bilateral superior temporal cortex (secondary and
      higher-level auditory cortex) and of the inferior frontal cortex (anterior and
      posterior inferior frontal gyrus). The fiber connectivity was investigated by
      using probabilistic diffusion tensor based tractography. The results underscore
      several so far underestimated auditory pathway connections, especially for the
      processing of affective prosody, such as a right ventral auditory pathway. The
      results also suggest the existence of a dual-stream processing in the right
      hemisphere, and a general predominance of the dorsal pathways in both hemispheres
      underlying the neural processing of affective prosody in an extended temporo
      frontal network. 

PMID- 25583614
TI  - HPA axis genetic variation, pubertal status, and sex interact to predict amygdala
      and hippocampus responses to negative emotional faces in school-age children.
AB  - Accumulating evidence suggests a role for stress exposure, particularly during
      early life, and for variation in genes involved in stress response pathways in
      neural responsivity to emotional stimuli. Understanding how individual
      differences in these factors predict differences in emotional responsivity may be
      important for understanding both normative emotional development and for
      understanding the mechanisms underlying internalizing disorders, like anxiety and
      depression, that have often been related to increased amygdala and hippocampus
      responses to negatively valenced emotional stimuli. The present study examined
      whether stress exposure and genetic profile scores (10 single nucleotide
      polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1,
      NR3C2, NR3C1, and FKBP5) predict individual differences in amygdala and
      hippocampus responses to fearful vs. neutral faces in school-age children (7-12
      year olds; N = 107). Experience of more stressful and traumatic life events
      predicted greater left amygdala responses to negative emotional stimuli. Genetic
      profile scores interacted with sex and pubertal status to predict amygdala and
      hippocampus responses. Specifically, genetic profile scores were a stronger
      predictor of amygdala and hippocampus responses among pubertal vs. prepubertal
      children where they positively predicted responses to fearful faces among
      pubertal girls and positively predicted responses to neutral faces among pubertal
      boys. The current results suggest that genetic and environmental stress-related
      factors may be important in normative individual differences in responsivity to
      negative emotional stimuli, a potential mechanism underlying internalizing
      disorders. Further, sex and pubertal development may be key moderators of the
      effects of stress-system genetic variation on amygdala and hippocampus
      responsivity, potentially relating to sex differences in stress-related
      psychopathology.

PMID- 25583615
TI  - Cortical reinstatement and the confidence and accuracy of source memory.
AB  - Cortical reinstatement refers to the overlap between neural activity elicited
      during the encoding and the subsequent retrieval of an episode, and is held to
      reflect retrieved mnemonic content. Previous findings have demonstrated that
      reinstatement effects reflect the quality of retrieved episodic information as
      this is operationalized by the accuracy of source memory judgments. The present
      functional magnetic resonance imaging (fMRI) study investigated whether
      reinstatement-related activity also co-varies with the confidence of accurate
      source judgments. Participants studied pictures of objects along with their
      visual or spoken names. At test, they first discriminated between studied and
      unstudied pictures and then, for each picture judged as studied, they also judged
      whether it had been paired with a visual or auditory name, using a three-point
      confidence scale. Accuracy of source memory judgments- and hence the quality of
      the source-specifying information--was greater for high than for low confidence
      judgments. Modality-selective retrieval-related activity (reinstatement effects)
      also co-varied with the confidence of the corresponding source memory judgment.
      The findings indicate that the quality of the information supporting accurate
      judgments of source memory is indexed by the relative magnitude of content
      selective, retrieval-related neural activity.

PMID- 25583616
TI  - Protocolized fluid therapy in brain-dead donors: the multicenter randomized
      MOnIToR trial.
AB  - BACKGROUND: Critical shortages of organs for transplantation jeopardize many
      lives. Observational data suggest that better fluid management for deceased organ
      donors could increase organ recovery. We conducted the first large multicenter
      randomized trial in brain-dead donors to determine whether protocolized fluid
      therapy increases the number of organs transplanted. METHODS: We randomly
      assigned donors to either protocolized or usual care in eight organ procurement
      organizations. A "protocol-guided fluid therapy" algorithm targeting the cardiac
      index, mean arterial pressure and pulse pressure variation was used. Our primary
      outcome was the number of organs transplanted per donor, and our primary analysis
      was intention to treat. Secondary analyses included: (1) modified intention to
      treat where only subjects able to receive the intervention were included and (2)
      12-month survival in transplant recipients. The study was stopped early. RESULTS:
      We enrolled 556 donors: 279 protocolized care and 277 usual care. Groups had
      similar characteristics at baseline. The study protocol could be implemented in
      76 % of subjects randomized to the intervention. There was no significant
      difference in mean number of organs transplanted per donor: 3.39 organs per donor
      (95 % CI 3.14-3.63) with protocolized care compared to 3.29 usual care (95 % CI
      3.04-3.54; mean difference, 0.1, 95 % CI -0.25 to 0.45; p = 0.56). In modified
      intention-to-treat analysis the mean number of organs increased (3.52 organs per
      donor, 95 % CI 3.23-3.8), but not statistically significantly (mean difference,
      0.23, 95 % CI -0.15 to 0.61; p = 0.23). Among the 1,430 recipients of organs from
      study subjects with data available, 56 deaths (7.8 %) occurred in the
      protocolized care arm and 56 (7.9 %) in the usual care arm in the first year
      (hazard ratio: 0.97, p = 0.86). CONCLUSIONS: In brain-dead organ donors, protocol
      guided fluid therapy compared to usual care may not increase the number of organs
      transplanted per donor.

PMID- 25583617
TI  - Prognosis of very preterm infants with severe respiratory distress syndrome
      receiving mechanical ventilation.
AB  - OBJECTIVE: To evaluate the prognosis of very preterm infants with severe
      respiratory distress syndrome (RDS) receiving mechanical ventilation. METHODS: A
      total of 288 preterm infants mechanically ventilated for severe RDS and completed
      follow-up till 18 months of corrected age comprised these study subjects. The
      associations of prenatal and postnatal factors, mode and duration of conventional
      mechanical ventilation (CMV), medication and treatment, and complications with
      cerebral palsy or mental developmental index (MDI) < 70 at 18 months of age were
      analyzed. RESULTS: The incidences of CP among study subjects were 17, 5, and 2%
      in infants less than 28, 28-30, and 30-32 weeks, respectively. The incidences of
      MDI < 70 were 49, 24, and 13% in infants less than 28 weeks, 28-30 weeks, and 30
      32 weeks, respectively. Antenatal corticosteroids, preeclampsia, fetal distress,
      early and late bacteremia, and decreased weight gain were associated with CP and
      an MDI < 70. In the CP and MDI < 70 groups, the number of infants on CMV was
      significantly higher than on high-frequency oscillatory ventilation (HFOV).
      Longer duration of mechanical ventilation and blood transfusions were associated
      with an increased risk of having an MDI < 70 or CP. The complications in study
      subjects associated with an MDI < 70 or CP were BPD, NEC, and IVH grade III-IV.
      CONCLUSION: The prognosis of very preterm infants with severe RDS may be
      influenced by several prenatal and postnatal factors. HFOV although decreased the
      duration of mechanical ventilation, whether it will decrease the incidence of
      neurodevelopmental disability, needs to be explored further.

PMID- 25583618
TI  - Comparison of frequency and time domain electromyography parameters in women with
      patellofemoral pain.
AB  - BACKGROUND: Despite its high incidence, patellofemoral pain etiology remains
      unclear. No prior study has compared surface electromyography frequency domain
      parameters and surface electromyography time domain variables, which have been
      used as a classic analysis of patellofemoral pain. METHODS: Thirty one women with
      patellofemoral pain and twenty eight pain-free women were recruited. Each
      participant was asked to descend a seven step staircase and data from five
      successful trials were collected. During the task, the vastus medialis and vastus
      lateralis muscle activities were monitored by surface electromyography. The data
      were processed and analyzed in four variables of the frequency domain (median
      frequency, low, medium and high frequency bands) and three time domain variables
      (Automatic, Cross-correlation and Visual Onset between the vastus medialis and
      vastus lateralis muscles). Reliability, Receiver Operating Characteristic curves
      and regression models were performed. FINDINGS: The medium frequency band was the
      most reliable variable and different between the groups for both muscles, also
      demonstrated the best values of sensitivity and sensibility, 72% and 69% for the
      vastus medialis and 68% and 62% for the vastus lateralis, respectively. The
      frequency variables predicted the pain of individuals with patellofemoral pain,
      26% for the vastus medialis and 20% for the vastus lateralis, being better than
      the time variables, which achieved only 7%. INTERPRETATION: The frequency domain
      parameters presented greater reliability, diagnostic accuracy and capacity to
      predict pain than the time domain variables during stair descent and might be a
      useful tool to diagnose individuals with patellofemoral pain.

PMID- 25583620
TI  - Antihypertensive therapy in 2014: Linking pathophysiology to antihypertensive
      treatment.

PMID- 25583621
TI  - Early detection of pulmonary arterial hypertension: do not forget the right
      ventricle.

PMID- 25583622
TI  - Antithrombotic therapy in 2014: Making headway in anticoagulant and antiplatelet
      therapy.

PMID- 25583623
TI  - One-step generation of multipartite entanglement among nitrogen-vacancy center
      ensembles.
AB  - We describe a one-step, deterministic and scalable scheme for creating
      macroscopic arbitrary entangled coherent states (ECSs) of separate nitrogen
      vacancy center ensembles (NVEs) that couple to a superconducting flux qubit. We
      discuss how to generate the entangled states between the flux qubit and two NVEs
      by the resonant driving. Then the ECSs of the NVEs can be obtained by projecting
      the flux qubit, and the entanglement detection can be realized by transferring
      the quantum state from the NVEs to the flux qubit. Our numerical simulation shows
      that even under current experimental parameters the concurrence of the ECSs can
      approach unity. We emphasize that this method is straightforwardly extendable to
      the case of many NVEs. 

PMID- 25583619
TI  - A major role for cardiovascular burden in age-related cognitive decline.
AB  - The incidence of dementia and cardiovascular disease (CVD) increases with age.
      Current evidence supports the role for both atherosclerosis and arteriosclerosis
      as a common pathophysiological ground for the heart-brain connection in ageing.
      Cognitive decline and CVDs share many vascular risk factors (VRFs) such as
      smoking, hypertension, and diabetes mellitus; furthermore, CVDs can contribute to
      cognitive decline by causing cerebral hypoperfusion, hypoxia, emboli, or
      infarcts. Mixed dementia, resulting from both cerebrovascular lesions and
      neurodegeneration, accounts for the majority of dementia cases among very old
      individuals (>=75 years). An accumulation of multiple VRFs, especially in middle
      age (40-59 years of age), can substantially increase dementia risk. The suggested
      declining trend in dementia risk, occurring in parallel with the decreasing
      incidence of cardiovascular events in high-income countries, supports the role of
      cardiovascular burden in dementia. Accordingly, strategies to promote
      cardiovascular health, especially if implemented from early life, might help to
      delay the onset of dementia. In this Review, we discuss the literature
      investigating the association of cardiovascular burden with cognitive decline and
      dementia over the life-course. 

PMID- 25583625
TI  - H2 adsorption on Ag-nanocluster/single-walled carbon nanotube composites: a
      molecular dynamics study on the effects of nanocluster size, diameter, and
      chirality of nanotube.
AB  - The H2 physisorption on AgN (with N = 32, 108, 256, 500, and 864)/carbon nanotube
      (CNT; in armchair and zigzag structures with diameters between 0.54 and 2.98 nm)
      composites were studied by molecular dynamic simulation to investigate the effect
      of nanocluster size, diameter, and chirality of nanotube on the adsorption
      phenomena. The calculations indicate that the effects of nanocluster properties
      are more important than those of the nanotube, in such a way that increase of
      nanocluster size, decreases the H2 adsorption. Also, the diameter and chirality
      of CNTs have considerable influence on the adsorption phenomena. As the diameter
      of nanotube is increased, the amount of adsorption is decreased. Moreover, H2
      molecules have more tendencies to those nanoclusters located on the armchair
      nanotubes than the zigzag ones. Another important result is the reversibility of
      H2 adsorption on these materials in which the structure of composite in vacuum
      and after reduction of H2 pressure to zero, is not changed, considerably.

PMID- 25583624
TI  - [Physical activity and biological maturation: a systematic review].
AB  - OBJECTIVE: To analyze the association between physical activity (PA) and
      biological maturation in children and adolescents. DATA SOURCE: We conducted a
      systematic review in April 2013 in the electronic databases of PubMed/Medline,
      SportDiscus, Web of Science and Lilacs without time restrictions. A total of 628
      articles potentially relevant were identified and 10 met the inclusion criteria
      for this review: cross-sectional or longitudinal studies, published in
      Portuguese, English or Spanish, with schoolchildren aged 9-15 year old of both
      sexes. DATA SYNTHESIS: Despite the heterogeneity of the studies, there was an
      inverse association between PA and biological maturation. The PA decreases with
      increased biological and chronological age in both sexes. Boys tend to be more
      physically active than girls; however, when controlling for biological age, the
      sex differences disappear. The association between PA and timing of maturation
      varies between the sexes. Variation in the timing of biological maturation
      affects the tracking of PA in early adolescent girls. This review suggests that
      mediators (BMI, depression, low self-esteem, and concerns about body weight) can
      explain the association between PA and biological maturation. CONCLUSIONS: There
      is a relationship between PA and biological maturation. PA decreases with
      increasing biological age with no differences between sexes. As for the timing of
      biological maturation, this relationship varies between sexes.

PMID- 25583626
TI  - Juxtaposed right atrial appendage in complex Transposition of the Great Arteries.

PMID- 25583627
TI  - Aortic pseudocoarctation associated with polysplenia/heterotaxy syndrome.
AB  - Polysplenia/heterotaxy syndrome is a rare congenital disorder associated with a
      wide spectrum of anomalies in various organ systems. Although anomalies of the
      cardiovascular system are common in this syndrome, the authors report a rare case
      of polysplenia syndrome associated with aortic pseudocoarctation, which to our
      knowledge has never been reported. 

PMID- 25583628
TI  - From ventriculomegaly to severe muscular atrophy: expansion of the clinical
      spectrum related to mutations in AIFM1.
AB  - The apoptosis-inducing factor (AIF) functions as a FAD-dependent NADH oxidase in
      mitochondria. Upon apoptotic stimulation it is released from mitochondria and
      migrates to the nucleus where it induces chromatin condensation and DNA
      fragmentation. So far mutations in AIFM1, a X-chromosomal gene coding for AIF,
      have been described in three families with 11 affected males. We report here on a
      further patient thereby expanding the clinical and mutation spectrum. In
      addition, we review the known phenotypes related to AIFM1 mutations. The clinical
      course in the male patient described here was characterized by phases with rapid
      deterioration and long phases without obvious progression of disease. At age 2.5
      years he developed hearing loss and severe ataxia and at age 10 years muscle
      wasting, swallowing difficulties, respiratory insufficiency and external
      opthamoplegia. By next generation sequencing of whole exome we identified a
      hemizygous missense mutation in the AIFM1 gene, c.727G>T (p.Val243Leu) affecting
      a highly conserved residue in the FAD-binding domain. Summarizing what is known
      today, mutations in AIFM1 are associated with a progressive disorder with
      myopathy, ataxia and neuropathy. Severity varies greatly even within one family
      with onset of symptoms between birth and adolescence. 3 of 12 patients died
      before age 5 years while others were still able to walk during young adulthood.
      Less frequent symptoms were hearing loss, seizures and psychomotor regression.
      Results from clinical chemistry, brain imaging and muscle biopsy were unspecific
      and inconsistent.

PMID- 25583629
TI  - Pharmacological interventions for the treatment of Achilles tendinopathy: a
      systematic review of randomized controlled trials.
AB  - INTRODUCTION: Several pharmacological interventions have been proposed for the
      management of Achilles tendinopathy, with no agreement on which is the overall
      best option available. This systematic review investigates the efficacy and
      safety of different local pharmacological treatments for Achilles tendinopathy.
      SOURCES OF DATA: We included only randomized controlled studies (RCTs) focusing
      on clinical and functional outcomes of therapies consisting in injection of a
      substance or local application. Assessment of the methodological quality was
      performed using a modified version of the Coleman methodology score (CMS) to
      determine possible risks of bias. AREAS OF AGREEMENT: Thirteen RCTs were included
      with a total of 528 studied patients. Eleven studies reported the outcomes of
      injection therapies. Two studies examined the outcomes of patients who applied
      glyceryl trinitrate patch. The mean modified CMS was 70.6 out of 90. AREAS OF
      CONTROVERSY: There was no significant evidence of remarkable benefits provided by
      any of the therapies studied. GROWING POINTS: There is not univocal evidence to
      advise any particular pharmacological treatment as the best advisable non
      operative option for Achilles tendinopathy as equivalent alternative to the most
      commonly used eccentric loading rehabilitation program. However, potential was
      shown by the combination of different substances administered with physical
      therapy. RESEARCH: There is a need for more long-term investigations, studying
      large enough cohort with standardized scores and evaluations shared by all the
      investigations to confirm the healing potential, and provide a stronger
      statistical comparison of the available treatments.

PMID- 25583632
TI  - Mutual solubilities between water and non-aromatic sulfonium-, ammonium- and
      phosphonium-hydrophobic ionic liquids.
AB  - Although previous studies attempted to characterize the liquid-liquid phase
      behaviour between water and ionic liquids (ILs), the impact of non-cyclic cations
      on the solubilities is poorly studied and yet to be understood. In this work, the
      mutual solubilities between water and ILs containing the anion
      bis(trifluoromethylsulfonyl)imide, [NTf2](-), combined with the cations
      diethylmethylsulfonium, [S221][NTf2], triethylsulfonium, [S222][NTf2],
      butyltrimethylammonium, [N4111][NTf2], tributylmethylammonium, [N4441][NTf2],
      methyltrioctylammonium, [N1888][NTf2], and methyltrioctylphosphonium,
      [P1888][NTf2], from (288.15 to 318.15) K and at 0.1 MPa, were experimentally
      measured and further compared with predictions from the COnductor-like Screening
      MOdel for Real Solvents (COSMO-RS). All the studied phase diagrams display an
      upper critical solution temperature (UCST). The binary system composed of
      [P1888][NTf2] exhibits the widest immiscibility gap, followed by [N18888][NTf2],
      [N4441][NTf2], [S222][NTf2], [N4111][NTf2], and [S221][NTf2]. The COSMO-RS is
      able to correctly predict the experimental UCST behaviour and the cation impact
      on the immiscibility regimes observed. Natural Population Analysis (NPA)
      calculations were additionally performed for the isolated cations in the gas
      phase indicating that the differences in the water-IL mutual miscibilities might
      not result only from the hydrophobicity of the cation (derived from the increase
      of the alkyl chains length) but also from the charge distribution of the central
      atom and attached methylene groups. This fact explains the enhanced solubility of
      ammonium-based ILs in water here identified. 

PMID- 25583631
TI  - Residual hearing preservation after cochlear implantation via round window or
      cochleostomy approach.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of the study was to investigate whether
      cochlear implantation using the round window approach provided better
      preservation of residual hearing than the cochleostomy approach. STUDY DESIGN:
      Case-control study. METHODS: We designed a case-control study including 40
      patients from a tertiary referral center who underwent cochlear implantation
      surgeries using devices from MED-EL Co., Innsbruck, Austria. Between November
      2013 and July 2014, we prospectively enrolled 20 subjects for cochlear
      implantation surgery using the round window insertion approach. In addition, 20
      age- and sex-matched control subjects from the database of cochlear implantees
      treated using the cochleostomy approach between January 2008 and October 2013
      were retrospectively enrolled. The residual hearing of the operated ear was
      measured before and after surgery. The variables analyzed were the pure-tone
      average threshold at 250, 500, and 1,000 Hz and the residual hearing at
      frequencies of 250 to 8,000 Hz. The residual hearing was considered as preserved
      when the audiometric changes were <10 dB hearing loss for each variable. The
      audiological results of the two groups were compared. RESULTS: No statistically
      significant difference in the preservation of residual hearing was found in the
      two groups (P > .05 for all of the variables). CONCLUSIONS: The round window and
      cochleostomy approaches for cochlear implant surgery may preserve residual
      hearing at similar rates across a range of frequencies.

PMID- 25583634
TI  - Photodriven [2]rotaxane-[2]catenane interconversion.
AB  - A [2]rotaxane, whose thread component comprises a central dibenzylammonium group
      and 9-alkoxyanthracene stoppers and is hosted by a 24-dibenzo-8-crown bead,
      undergoes an efficient photocatenation step resulting in a [2]rotaxane-to
      [2]catenane topology interconversion via a fully reversible [4pi+4pi]
      photocyclomerization of terminal anthracene groups. 

PMID- 25583633
TI  - Evaluation of the impact of sulfobutylether7 -beta-cyclodextrin on the liquid
      chromatography-mass spectrometry analysis of biological samples arising from in
      vivo pharmacokinetic studies.
AB  - The utility of cyclodextrin (CD) complexation in improving apparent solubility of
      drugs in parenteral formulations is well established. Administration of these
      formulations delivers CD directly into the systemic circulation, and it may be
      necessary to demonstrate unaltered in vivo disposition of a drug coadministered
      with a CD. Crucial to the undertaking of such a study is the need for
      bioanalytical assays in which CD presence does not impact drug quantitation. This
      is of particular importance when assessing the potential impact of in vivo CD
      complexation on the urinary excretion of a drug, as CDs are predominantly
      eliminated via glomerular filtration, and hence are present in urine at
      significantly higher concentration than would be present in blood and plasma. Of
      23 publications (in the past 30 years) describing preclinical and clinical
      assessment of drug pharmacokinetics after i.v. administration of CD-enabled
      formulations, only two reports clearly stated that the presence of CD had no
      impact on assay performance. In this work, we describe the simple process
      involved in (1) predicting the maximum concentrations of a modified CD,
      sulfobutylether7 -beta-CD (SBE7 -beta-CD), in plasma and urine samples from
      preclinical studies, and (2) evaluating the impact of SBE7 -beta-CD on the
      quantitative liquid chromatography-mass spectrometry analysis of rimantadine.

PMID- 25583630
TI  - Role of strain values using automated function imaging on transthoracic
      echocardiography for the assessment of acute chest pain in emergency department.
AB  - Left ventricular strain echocardiography is reported to be more sensitive in
      detecting myocardial ischemia than conventional transthoracic echocardiography
      (TTE). We evaluated the usefulness of 2D strain analysis for the assessment of
      acute chest pain in emergency department (ED). Patients presenting to ED with
      acute chest pain were recruited. Patients with ST-elevation myocardial
      infarction, known coronary artery disease (CAD), non-ischemic cardiomyopathy, or
      non-cardiac chest pain were excluded. The pretest probability of CAD and TTEs
      were evaluated in all patients. TTEs included visual assessments of regional wall
      motion abnormality (RWMA) and analysis of global and regional longitudinal strain
      (GLS and RLS). The diagnosis of CAD and the occurrence of cardiac events during 1
      month after ED visit were reviewed. Cardiac events were observed in 25% of total
      104 patients, and CAD was detected in 36% of 69 patients with coronary imaging
      tests. Compared to RWMA, RLS showed higher sensitivity (sensitivity/specificity =
      64/89 vs. 92/77%) with similar diagnostic accuracy (79.7 vs. 82.6%, p = 0.791)
      for CAD. RLS also demonstrated better diagnostic performance than either GLS
      (sensitivity/specificity = 92/57%) or pretest probability
      (sensitivity/specificity = 72/64 %). Similarly, RLS had the higher predictive
      value for 1-month cardiac events. In multivariable analyses including pretest
      probability, LVEF, RWMA, cardiac enzyme, GLS, and RLS; only pretest probability
      (OR 1.91, 95% CI 1.22-2.99, p = 0.005) and RLS (OR 25.42, 95 % CI 1.84-342.04, p
      = 0.016) independently predicted CAD. Strain echocardiography appears to be
      effective in diagnosing CAD and predicting future events with high sensitivity
      and negative predictive value in acute chest pain patients visiting ED.

PMID- 25583635
TI  - Regulation of the mesolimbic dopamine circuit by feeding peptides.
AB  - Polypeptides produced in the gastrointestinal tract, stomach, adipocytes,
      pancreas and brain that influence food intake are referred to as 'feeding
      related' peptides. Most peptides that influence feeding exert an inhibitory
      effect (anorexigenic peptides). In contrast, only a few exert a stimulating
      effect (orexigenic peptides), such as ghrelin. Homeostatic feeding refers to when
      food consumed matches energy deficits. However, in western society where access
      to palatable energy-dense food is nearly unlimited, food is mostly consumed for
      non-homeostatic reasons. Emerging evidence implicates the mesocorticolimbic
      circuitry, including dopamine neurons of the ventral tegmental area (VTA), as a
      key substrate for non-homeostatic feeding. VTA dopamine neurons encode cues that
      predict rewards and phasic release of dopamine in the ventral striatum motivates
      animals to forage for food. To elucidate how feeding-related peptides regulate
      reward pathways is of importance to reveal the mechanisms underlying non
      homeostatic or hedonic feeding. Here, we review the current knowledge of how
      anorexigenic peptides and orexigenic peptides act within the VTA. 

PMID- 25583636
TI  - Alpha2-adrenoceptor-independent inhibition of acetylcholine receptor channel and
      sodium channel by dexmedetomidine in rat superior cervical ganglion neurons.
AB  - Both central and peripheral sympathetic nervous systems contribute to the
      cardiovascular effects of dexmedetomidine (DMED), a highly selective and widely
      used a2-adrenoceptor agonist for sedation, analgesia, and stress management. The
      central sympatholytic effects are augmented by peripheral inhibition of
      sympathetic ganglion transmission. The mechanism is not clear. In this research,
      using conventional patch-clamp recordings we investigated the direct effects of
      DMED on sodium (Na(+)) channel currents (INa) and nicotinic acetylcholine (ACh)
      receptor (nAChRs) channel currents (IACh) in rat superior cervical ganglion (SCG)
      neurons to explore the possible mechanisms of sympathetic ganglion transmission
      inhibition by DMED. DMED voltage-dependently suppressed INa with half maximal
      inhibitory concentration (IC50) values of 67.2+/-9.6MUM and 26.1+/-5.3MUM at
      holding potentials of -80mV and -60mV, respectively. The inhibition of Na(+)
      channels by DMED was also frequency dependent. 100MUM DMED shifted the Na(+)
      channel inactivation curves to the hyperpolarizing direction by 9.8mV (P<0.01)
      and slowed the recovery from inactivation by 8.9ms (P<0.01), but no effects were
      seen on the shape of the current-voltage relationship or Na(+) channels
      activation curves. DMED dose-dependently inhibited IACh with an IC50 value of
      5.5+/-2.4MUM in SCG neurons, and this inhibition was voltage-independent. DMED
      pretreatment followed by fast co-application of DMED and ACh produced a
      significantly larger IACh inhibition than without DMED pretreatment. Yohimbine,
      phentolamine, and atropine pretreatment did not alter the inhibitory effects of
      DMED on INa and IACh. In conclusion, DMED dose-dependently inhibits INa and IACh
      in rat SCG neurons by preferential binding to the inactivated state of the Na(+)
      channels and the closed state (resting) of nAChR channels respectively. Both
      inhibitions are a2-adrenoceptor independent. Furthermore, the nAChR channels in
      rat SCG neurons are much more sensitive to inhibition by DMED than Na(+)
      channels. 

PMID- 25583637
TI  - Transcalvarial brain herniation volume after decompressive craniectomy is the
      difference between two spherical caps.
AB  - Decompressive craniectomy (DC) is a surgical procedure used to relieve severely
      increased intracranial pressure (ICP) by removing a portion of the skull.
      Following DC, the brain expands through the skull defect created by DC, resulting
      in transcalvarial herniation (TCH). Traditionally, people measure only changes in
      the ICP but not in the intracranial volume (ICV), which is equivalent to the
      volume of TCH (V(TCH)), in patients undergoing DC. We constructed a simple model
      of the cerebral hemispheres, assuming the shape of the upper half of a sphere
      with a radius of 8 cm. We hypothesized that the herniated brain following DC also
      conforms to the shape of a spherical cap. Considering that a circular piece of
      the skull with a radius of a was removed, V(TCH) is the volume difference between
      2 spherical caps at the operated side and the corresponding non-operated side,
      which represents the pre-DC volume underneath the removed skull due to the
      bilateral symmetry of the skull and the brain. Subsequently, we hypothesized that
      the maximal extent of TCH depends on a because of the biomechanical limitations
      imposed by the inelastic scalp. The maximum value of V(TCH) is 365.0 mL when a is
      7.05 cm and the height difference between the spherical caps (Deltah) at its
      maximum is 2.83 cm. To facilitate rapid calculation of V(TCH), we proposed a
      simplified estimation formula, V^(TCH)=1/2A(2)Deltah, where A=2a. With the a
      value ranging between 0 and 7 cm, the ratio between V^(TCH) and V(TCH) ranges
      between 0.77 and 1.27, with different Deltah values. For elliptical skull defects
      with base diameters of A and C, the formula changes to V^(TCH)=1/2ACDeltah. If
      our hypothesis is correct, surgeons can accurately calculate V(TCH) after DC.
      Furthermore, this can facilitate volumetric comparisons between the effects of
      DCs in skulls of varying sizes, allowing quantitative comparisons between ICVs in
      addition to ICPs.

PMID- 25583638
TI  - Individual risk factors for deep infection and compromised fracture healing after
      intramedullary nailing of tibial shaft fractures: a single centre experience of
      480 patients.
AB  - INTRODUCTION: Despite modern advances in the treatment of tibial shaft fractures,
      complications including nonunion, malunion, and infection remain relatively
      frequent. A better understanding of these injuries and its complications could
      lead to prevention rather than treatment strategies. A retrospective study was
      performed to identify risk factors for deep infection and compromised fracture
      healing after intramedullary nailing (IMN) of tibial shaft fractures. MATERIALS
      AND METHODS: Between January 2000 and January 2012, 480 consecutive patients with
      486 tibial shaft fractures were enrolled in the study. Statistical analysis was
      performed to determine predictors of deep infection and compromised fracture
      healing. Compromised fracture healing was subdivided in delayed union and
      nonunion. The following independent variables were selected for analysis: age,
      sex, smoking, obesity, diabetes, American Society of Anaesthesiologists (ASA)
      classification, polytrauma, fracture type, open fractures, Gustilo type, primary
      external fixation (EF), time to nailing (TTN) and reaming. As primary statistical
      evaluation we performed a univariate analysis, followed by a multiple logistic
      regression model. RESULTS: Univariate regression analysis revealed similar risk
      factors for delayed union and nonunion, including fracture type, open fractures
      and Gustilo type. Factors affecting the occurrence of deep infection in this
      model were primary EF, a prolonged TTN, open fractures and Gustilo type. Multiple
      logistic regression analysis revealed polytrauma as the single risk factor for
      nonunion. With respect to delayed union, no risk factors could be identified. In
      the same statistical model, deep infection was correlated with primary EF.
      CONCLUSIONS: The purpose of this study was to evaluate risk factors of poor
      outcome after IMN of tibial shaft fractures. The univariate regression analysis
      showed that the nature of complications after tibial shaft nailing could be
      multifactorial. This was not confirmed in a multiple logistic regression model,
      which only revealed polytrauma and primary EF as risk factors for nonunion and
      deep infection, respectively. Future strategies should focus on prevention in
      high-risk populations such as polytrauma patients treated with EF.

PMID- 25583639
TI  - [Psychiatric disorders revealing catastrophic celiac disease: a case report].

PMID- 25583640
TI  - Coalescence preference in densely packed microbubbles.
AB  - A bubble merged from two parent bubbles with different size tends to be placed
      closer to the larger parent. This phenomenon is known as the coalescence
      preference. Here we demonstrate that the coalescence preference can be blocked
      inside a densely packed cluster of bubbles. We utilized high-speed high
      resolution X-ray microscopy to clearly visualize individual coalescence events
      inside densely packed microbubbles with a local packing fraction of ~40%. The
      surface energy release theory predicts an exponent of 5 in a relation between the
      relative coalescence position and the parent size ratio, whereas our observation
      for coalescence in densely packed microbubbles shows a different exponent of 2.
      We believe that this result would be important to understand the reality of
      coalescence dynamics in a variety of packing situations of soft matter. 

PMID- 25583641
TI  - To study the effect of curcumin on the growth properties of circulating
      endothelial progenitor cells.
AB  - Curcumin has been shown to regulate the expression of genes implicated in tumor
      cell proliferation, metastasis, chemotherapy resistance, and angiogenesis.
      Endothelial progenitor cells (EPCs) have been recently described in the
      peripheral blood as cells contributing to both physiological and pathological
      angiogenesis. In the current study, we evaluated the effect of curcumin on these
      angiogenic cells. EPCs were isolated, expanded, and characterized ex vivo. These
      cells were then treated with different concentrations of curcumin. The formation
      of EPC colonies in culture and their proliferation was analyzed by 5'-bromo-2'
      deoxyuridine assays in absence and presence of curcumin. Further, the expression
      of two important cell cycle inhibitory proteins, p21 and p53, in the curcumin-
      and culture medium-treated cells without curcumin was evaluated by intracellular
      flow cytometry. The results showed that there was a significant decrease in the
      formation of EPC colonies in culture. EPC proliferation was significantly
      inhibited by curcumin in a dose-dependent manner. Flow cytometry analysis showed
      a twofold increase in the expression of both p21 and p53 in curcumin-treated
      cells as compared to the medium-treated cells, suggesting that curcumin inhibits
      EPC growth by mainly inhibiting the G1 to S phase transition in the cell cycle.
      It would be further worthwhile to study the effect of curcumin on EPC-mediated
      angiogenic activity. 

PMID- 25583643
TI  - Apolipoprotein E levels and Alzheimer risk.

PMID- 25583642
TI  - A novel approach for the intravenous delivery of leuprolide using core-cross
      linked polymeric micelles.
AB  - Therapeutic peptides are highly attractive drugs for the treatment of various
      diseases. However, their poor pharmacokinetics due to rapid renal elimination
      limits their clinical applications. In this study, a model hormone peptide,
      leuprolide, was covalently linked to core-cross-linked polymeric micelles (CCL
      PMs) via two different hydrolysable ester linkages, thereby yielding a
      nanoparticulate system with tuneable drug release kinetics. The ester linkage
      that provided the slowest peptide release kinetics was selected for in vivo
      evaluation. Compared to the soluble peptide, the leuprolide-entrapped CCL-PMs
      showed a prolonged circulation half-life (14.4h) following a single intravenous
      injection in healthy rats and the released leuprolide was detected in blood for
      3days. In addition, the area under the plasma concentration-time curve (AUC)
      value was >100-fold higher for leuprolide-entrapped CCL-PMs than for soluble
      leuprolide. Importantly, the released peptide remained biologically active as
      demonstrated by increased and long-lasting plasma testosterone levels. This study
      shows that covalent linkage of peptides to CCL-PMs via hydrolytically sensitive
      ester bonds is a promising approach to achieving sustained systemic levels of
      peptides after intravenous administration. 

PMID- 25583644
TI  - Magnetic particle imaging.

PMID- 25583645
TI  - Can we predict which patients will experience resolution of detrusor overactivity
      after transurethral resection of the prostate?
AB  - PURPOSE: We determined which clinical and urodynamic variables may be related to
      persistent detrusor overactivity after transurethral resection of the prostate.
      MATERIALS AND METHODS: We studied 46 patients with bladder outlet obstruction due
      to benign prostatic hyperplasia who were treated with transurethral prostate
      resection from 2011 to 2012. All patients underwent urodynamic analysis
      preoperatively and 12 months postoperatively. Clinical and urodynamic variables
      in the preoperative period were correlated with the resolution of detrusor
      overactivity postoperatively. RESULTS: Patients with detrusor overactivity in the
      preoperative period were older (65.2 vs 61.1 years, p = 0.041) and had a higher I
      PSS (International Prostate Symptom Score) (25.2 vs 19, p = 0.014) and higher
      maximum flow rate (8.6 vs 6.6 ml per second, p = 0.039). Patients with persistent
      detrusor overactivity were statistically older than those with resolution (69 vs
      63 years, p = 0.043). Detrusor overactivity persisted in 63.6% of patients with
      maximum cystometric capacity less than 250 ml compared to 20% of those with
      greater than 250 ml (p = 0.024). When analyzing urodynamic variables together, we
      found a 66.7% chance of persistent detrusor overactivity in patients with maximum
      cystometric capacity less than 250 ml and detrusor overactivity amplitude greater
      than 40 cm H2O (p = 0.041). When these characteristics were associated with early
      detrusor overactivity, the chance of persistent detrusor overactivity was 83.3%
      (p = 0.013). CONCLUSIONS: Advanced patient age together with low maximum
      cystometric capacity, and early and high detrusor overactivity amplitude are the
      most important predictors of persistent detrusor overactivity after relief of
      bladder outlet obstruction.

PMID- 25583646
TI  - Off-pump or on-pump beating heart: which technique offers better outcomes
      following coronary revascularization?
AB  - A best evidence topic was written according to a structured protocol. The
      question addressed was whether on-pump beating heart coronary artery bypass (BH
      ONCAB) surgery has a different outcome profile in comparison to off-pump coronary
      artery bypass (OPCAB). A total of 205 papers were found by systematic search of
      which 7 provided the largest and most recent outcome analysis comparing BH-ONCAB
      with OPCAB, and represented the best evidence to answer the clinical question.
      The authors, date, journal, study type, population, main outcome measures and
      results were tabulated. Reported outcome measures included mortality, stroke,
      myocardial infarction, renal failure, myocardial damage, change in ejection
      fraction, number of bypass grafts and completeness of revascularization. With the
      exception of one study that favoured the off-pump technique, our review did not
      demonstrate a statistically significant difference in terms of mortality between
      the groups. We did not identify a statistically significant difference in any
      reported morbidity outcomes. However, there was a trend towards better outcomes
      for the on-pump beating heart technique, despite a higher risk profile in terms
      of age, ejection fraction and burden of coronary disease in this group.
      Consistent statistically significant differences between the groups were the mean
      number of grafts performed and the completeness of revascularization, both of
      which were higher with the on-pump beating heart technique. Limitations to the
      current evidence include the finding that most of the current data arise from
      specialist off-pump surgeons or centres that would usually only carry out BH
      ONCAB in the higher risk patients where the added safety of cardiopulmonary
      bypass is desired. 

PMID- 25583647
TI  - Influence of previous percutaneous coronary intervention on clinical outcome of
      coronary artery bypass grafting: a meta-analysis of comparative studies?.
AB  - The prognostic significance of previous percutaneous coronary intervention (PCI)
      in patients undergoing coronary artery bypass grafting (CABG) is still unclear.
      Although many studies have reported adverse effects of previous PCI on
      postoperative mortality in CABG, as yet no meta-analysis has been carried out. We
      conducted this first meta-analysis to assess whether previous PCI increases
      postoperative mortality in CABG. MEDLINE and EMBASE were searched for relevant
      articles up to and including April 2014. Studies published in English satisfying
      the following criteria were included in the meta-analysis: (i) comparing CABG
      patients with previous PCI versus without previous PCI; and (ii) reporting
      hospital mortality. Our search identified 23 comparative studies, including 174
      777 patients: 19 179 with previous PCI and 155 598 without previous PCI. Pooled
      analysis demonstrated that previous PCI had an adverse effect on hospital
      mortality: odds ratio (OR) 1.187, 95% confidence interval (CI) 1.075-1.312.
      Furthermore, subgroup analysis stratified by the proportion of multiple previous
      PCI (i.e. number of patients with multiple previous PCI/number of patients with
      single or multiple previous PCI) was performed. In the subgroup of studies with
      the proportion <40%, the adverse effect was not significant: OR 0.897 (95% CI
      0.723-1.113); however, in the subgroup of studies with the proportion >= 40%, the
      adverse effect of previous PCI was significant: OR 1.987 (95% CI 1.563-2.526). A
      meta-regression coefficient was significantly positive for the proportion of
      patients with a history of multiple PCI (coefficient 0.841; 95% CI 0.457-1.226; P
      < 0.001). This meta-analysis would argue that as the proportion of patients with
      multiple previous PCI in the CABG cohort increases, postoperative mortality also
      increases. This result re-emphasizes the importance of the heart team approach to
      coronary revascularization.

PMID- 25583648
TI  - Surgical modification for preventing a gothic arch after aortic arch repair
      without the use of foreign material.
AB  - OBJECTIVES: Systemic hypertension is the main late complication after arch
      reconstruction in patients with arch obstruction. Gothic arch geometry is
      suspected to be one of its possible causes. Accordingly, we evaluated here if a
      modified arch repair technique using an autologous pulmonary patch is effective
      in preventing gothic arch development. METHODS: Fifty infants who underwent arch
      repair with either a modified (n = 17) or conventional (n = 33) technique between
      January 2006 and August 2012 by a single surgeon were retrospectively reviewed.
      Arch geometry was compared using three categories (gothic, crenel or roman),
      classified by the height/width (H/W) ratio and the arch angle measured in
      computed tomography. RESULTS: No gothic arch geometry was observed in the
      modified group, whereas it was observed in 9 cases in the conventional group (P =
      0.005). Moreover, reintervention for arch restenosis was performed only in the
      conventional group (n = 4; P = 0.29). No associated complications were observed,
      although the selective cerebral perfusion time was longer in the modified group
      than in the conventional group (28.5 +/- 6.2 vs 17.1 +/- 9.9 min; P < 0.001).
      Otherwise, there were no significant differences in clinical variables between
      the groups. The mean follow-up duration was 55.3 +/- 26.7 months. Significant
      systemic hypertension was not observed in our study cohort. CONCLUSIONS: Our
      modified technique was proven to be not only highly effective in preventing
      gothic arch geometry, but also as equally safe in terms of early clinical
      outcomes as conventional arch reconstruction techniques.

PMID- 25583649
TI  - A genome-wide association study for nutritional indices in Drosophila.
AB  - Individuals are genetically variable for the way in which they process nutrients
      and in the effects of dietary content on reproductive success, immunity, and
      development. Here, we surveyed genetic variation for nutrient stores (glucose,
      glycogen, glycerol, protein, triglycerides, and wet weight) in the Drosophila
      Genetic Reference Panel (DGRP) after rearing the flies on either a low-glucose or
      high-glucose diet. We found significant genetic variation for these nutritional
      phenotypes and identified candidate genes that underlie that variation using
      genome-wide associations. In addition, we found several significant correlations
      between the nutritional phenotypes measured in this study and other previously
      published phenotypes, such as starvation stress resistance, oxidative stress
      sensitivity, and endoplasmic reticulum stress, which reinforce the notion that
      these lines can be used to robustly measure related phenotypes across distinct
      laboratories. 

PMID- 25583650
TI  - Intersphincteric resection and hand-sewn coloanal anastomosis for low rectal
      cancer: Short-term outcomes in the Indian setting.
AB  - INTRODUCTION: The rectum remains a predominant subsite of colorectal cancer in
      the Indian population. Unique to the Indian setting are significant social
      repercussions associated with a permanent stoma. On account of this, many
      patients who are advised abdominal perineal excision of the rectum (APER) default
      treatment. Accurate demonstration of the intersphincteric plane with magnetic
      resonance imaging has made intersphincteric resection (ISR) a viable option. This
      study is aimed at determining the feasibility and oncological adequacy of ISR in
      the Indian scenario. MATERIAL AND METHODS: All patients with low rectal cancer
      who underwent an ISR at the Tata Memorial Centre, from July 2013 to December 2013
      were included. Patients with invasion of the external sphincter and suboptimal
      preoperative sphincter function were excluded. Following standard preoperative
      staging, patients with a threatened circumferential resection margin (CRM) and/or
      mesorectal nodes were given preoperative chemoradiotherapy. The oncological
      adequacy of the procedure was evaluated in terms of margin positivity (distal and
      CRMs) and lymph node yield. Short-term perioperative outcomes included 30-day
      mortality, postoperative morbidity, anastomotic leaks, and length of hospital
      stay. RESULTS: Thirty-three patients with low rectal cancer and a median age of
      38 years underwent ISR during the defined study period. Twenty-three patients (70
      %) underwent open surgery whereas ten patients received a laparoscopic resection.
      The median blood loss and hospital stay was 300 mL and 7 days, respectively. Two
      patients had an involved CRM, but all distal margins were free of tumor. The
      quality of total mesorectal excision was satisfactory in all patients with a
      median lymph node yield of 9 nodes. CONCLUSIONS: Intersphincteric resection is
      feasible and oncologically safe in selected patients with low rectal cancer. Long
      term functional and oncological outcomes are essential before it can be
      considered a viable alternative to APER.

PMID- 25583651
TI  - Etiological spectrum of motor dysphagia as per Chicago Classification--Experience
      at a tertiary center in Central India.

PMID- 25583652
TI  - Enhanced light out-coupling efficiency of organic light-emitting diodes with an
      extremely low haze by plasma treated nanoscale corrugation.
AB  - Extremely low-haze light extraction from organic light-emitting diodes (OLEDs)
      was achieved by utilizing nanoscale corrugation, which was simply fabricated with
      plasma treatment and sonication. The haze of the nanoscale corrugation for light
      extraction (NCLE) corresponds to 0.21% for visible wavelengths, which is
      comparable to that of bare glass. The OLEDs with NCLE showed enhancements of
      34.19% in current efficiency and 35.75% in power efficiency. Furthermore, the
      OLEDs with NCLE exhibited angle-stable electroluminescence (EL) spectra for
      different viewing angles, with no change in the full width at half maximum (FWHM)
      and peak wavelength. The flexibility of the polymer used for the NCLE and plasma
      treatment process indicates that the NCLE can be applied to large and flexible
      OLED displays. 

PMID- 25583654
TI  - Successful Application of Add-on Transcranial Direct Current Stimulation (tDCS)
      for Treatment of SSRI Resistant OCD.

PMID- 25583653
TI  - Effects of Electrode Drift in Transcranial Direct Current Stimulation.
AB  - BACKGROUND: Conventional transcranial direct current stimulation (tDCS) methods
      involve application of weak electrical current through electrodes encased in
      saline-soaked sponges affixed to the head using elastic straps. In the absence of
      careful preparation, electrodes can drift from their original location over the
      course of a tDCS session. OBJECTIVE: The current paper investigates the influence
      of electrode drift on distribution of electric fields generated by conventional
      tDCS. METHODS: MRI-derived finite element models of electric fields produced by
      tDCS were used to investigate the influence of incremental drift in electrodes
      for two of the most common electrode montages used in the literature: M1/SO
      (motor to contralateral supraorbital) and F3/F4 (bilateral frontal). Based on
      these models, we extracted predicted current intensity from 20 representative
      structures in the brain. RESULTS: Results from separate RM-ANOVAs for M1/SO and
      F3/F4 montages demonstrated that 5% incremental drift in electrode position
      significantly changed the distribution of current delivered by tDCS to the human
      brain (F's > 8.6, P's < 0.001). Pairwise comparisons demonstrated that as little
      as 5% drift was able to produce significant differences in current intensity in
      structures distributed across the brain (P's < 0.03). CONCLUSIONS: Drift in
      electrode position during a session of tDCS produces significant alteration in
      the intensity of stimulation delivered to the brain. Elimination of this source
      of variability will facilitate replication and interpretation of tDCS findings.
      Furthermore, measurement and statistically accounting for drift may prove
      important for better characterizing the effects of tDCS on the human brain and
      behavior.

PMID- 25583655
TI  - Double PCL sign does not always indicate a bucket-handle tear of medial meniscus.
AB  - The discoid medial meniscus is an extremely rare anomaly. Bilateral discoid
      medial menisci are much more rare but intermittently reported. We report the
      first case of bilateral discoid medial menisci with positive double PCL sign,
      which typically indicates a bucket-handle tear of medial meniscus. A literature
      review was also conducted on bilateral discoid medial menisci. 

PMID- 25583656
TI  - Is the cognitive triad a clear marker of depressive symptoms in youngsters?
AB  - Research on depression showed patterns of maladaptive thinking reflecting themes
      of negative self-evaluation, a pessimistic view on the world and hopelessness
      regarding the future, the so-called cognitive triad. However, it is still unclear
      if these cognitive aspects are also a clear marker of depressive symptoms in
      children. Therefore in the current study we will investigate to what extent the
      cognitive triad contributes to the prediction of depressive symptoms. Four
      hundred and seventy-one youngsters with a mean age of 12.41 years, of which 53%
      were male, participated in this study. They filled in self-report questionnaires
      to measure depressive symptoms, anxious symptoms, emotional and behavioral
      problem behavior and the cognitive triad. The cognitive triad explained 43.5% of
      the variance in depressive symptoms as reported by the children themselves
      without controlling for comorbid psychopathology. When controlling for comorbid
      anxiety and externalizing behavior problems, adding the cognitive triad
      contributes to depressive symptoms with 11% on top of the 45% explained variance
      by comorbid problems. The findings were observed both in the child (10-12 years)
      and adolescent (13-15 years) subsample. The standardized betas for the view on
      the World were low and did only reach the significance level in the adolescent
      sample. The cognitive triad represents a key component of depressive symptoms,
      also in younger age groups. Specifically the negative view on the Self and the
      negative view on the Future is already associated with depressive symptoms in
      both the child and adolescent subsample. The common variance among different
      psychopathologies (depression, anxiety and behavioral problems) still needs to be
      sorted out clearly.

PMID- 25583657
TI  - Body adiposity index as marker of obesity and cardiovascular risk in adults from
      Bogota, Colombia.
AB  - OBJECTIVE: To assess the value of body adiposity index (BAI) as a marker of
      obesity and predictor of cardiovascular disease (CVD). MATERIALS AND METHODS: A
      cross-sectional study in 527 volunteers from the education and automotive sector
      in Bogota, Colombia. BAI was calculated using the Bergman et al. equation ([hip
      circumference in cm)/[height in m(2)](1,5)-18]). Anthropometric, clinical and
      laboratory data were collected, cholesterol/HDL-C, LDL-C/HDL-C; triglycerides/HDL
      C and lipid-metabolic index (LMI) ratios were calculated. Prevalence rates and
      means, according to tertiles (T), and multivariate analysis between the BAI and
      anthropometric, clinical, and laboratory markers were estimated. RESULTS: Obesity
      prevalence was 33.9% (BAI>27.5%). Subjects with lower BAI (T-1) had lower
      cholesterol, triglycerides/HDL-C, and cholesterol/HDL-C levels and better LMI;
      P<.001. The multivariate model showed in T-3 subjects an OR 3.33 (95% CI 2.16 to
      5.13) for central obesity and an OR 3.39 (95% CI 2.34 to 4.90) for increased
      visceral fat. As regards lipid and carbohydrate metabolism, BAI was able to
      predict the risk OR 7.95 (95% CI 4.88 to 12.94), OR 1.60 (95% CI 1.03 to 2.41),
      OR 1.69 (95% CI 1.06 to 2.70) and OR 9.27 (95% CI 2.01 to 21.80), shows a
      significant association between cholesterol, triglycerides, LDL cholesterol and
      glucose respectively, P<0.001. CONCLUSION: A high prevalence of obesity by BAI
      was observed, and statistically positive associations with cardiovascular risk
      factors were shown.

PMID- 25583658
TI  - Spanish consensus for the management of patients with anaplastic cell thyroid
      carcinoma.
AB  - Anaplastic thyroid cancer (ATC) is the most aggressive solid tumour known and is
      a rare but highly lethal form of thyroid cancer that requires a multidisciplinary
      team approach. No Spanish consensus exists for management of patients with ATC.
      The Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition
      and the GETHI (Grupo Espanol de Enfermedades Huerfanas e Infrecuentes) of the
      Spanish Society of Oncology, in agreement with the Boards of these Societies,
      commissioned an independent task force to develop a wide consensus on ATC. The
      relevant literature was reviewed, including serial PubMed searches supplemented
      with additional articles. The consensus includes the characteristics, diagnosis,
      initial evaluation, establishment of treatment goals, approaches to locoregional
      disease (surgery, radiotherapy, systemic therapy, supportive care during active
      treatment), approaches to advanced/metastatic disease, palliative care options,
      monitoring, and long-term follow-up of ATC. For operable disease, a combination
      of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such
      as doxorubicin, cisplatin and paclitaxel, is the best treatment strategy.
      Cytotoxic drugs are poorly effective for advanced/metastatic ATC. On the other
      hand, targeted agents may represent a viable therapeutic option. Patients with
      stage IVA/IVB resectable disease have the best prognosis, particularly if a
      multimodal approach is used, and some stage IVB unresectable patients may respond
      to aggressive therapy. Patients with stage IVC disease should be considered for
      clinical trials or for hospice/palliative care depending on their preference.
      This is the first Spanish consensus for ATC, and provides recommendations for
      management of this extremely aggressive malignancy. Novel systemic therapies are
      being tested, and more effective combinations are needed to improve patient
      outcomes. Although more aggressive radiotherapy has reduced locoregional
      recurrence, mean overall survival has not improved in the past 50 years. 

PMID- 25583659
TI  - Pulmonary surfactant in the airway physiology: a direct relaxing effect on the
      smooth muscle.
AB  - Beside alveoli, surface active material plays an important role in the airway
      physiology. In the upper airways it primarily serves in local defense. Lower
      airway surfactant stabilizes peripheral airways, provides the transport and
      defense, has barrier and anti-edematous functions, and possesses direct relaxant
      effect on the smooth muscle. We tested in vitro the effect of two surfactant
      preparations Curosurf(r) and Alveofact(r) on the precontracted smooth muscle of
      intra- and extra-pulmonary airways. Relaxation was more pronounced for lung
      tissue strip containing bronchial smooth muscle as the primary site of surfactant
      effect. The study does not confirm the participation of ATP-dependent potassium
      channels and cAMP-regulated epithelial chloride channels known as CFTR chloride
      channels, or nitric oxide involvement in contractile response of smooth muscle to
      surfactant.By controlling wall thickness and airway diameter, pulmonary
      surfactant is an important component of airway physiology. Thus, surfactant
      dysfunction may be included in pathophysiology of asthma, COPD, or other diseases
      with bronchial obstruction.

PMID- 25583660
TI  - Neuromolecular mechanisms mediating the effects of chronic intermittent hypoxia
      on adrenal medulla.
AB  - Sleep disordered breathing (SDB) with recurrent apnea is a major health problem
      affecting several million adult men and women. Humans with SDB are prone to
      develop hypertension. Studies on rodents established that exposure to chronic
      intermittent hypoxia (CIH) alone is sufficient to induce hypertension similar to
      that seen in patients with SDB. Available evidence from studies on experimental
      animals suggests that catecholamines secreted from adrenal medulla (AM), an end
      organ of the sympathetic nervous system is a major contributor to CIH-induced
      hypertension. In this article, we present an overview of our current
      understanding on how CIH reconfigures AM function and highlight recent findings
      on the underlying cellular and molecular mechanisms. 

PMID- 25583661
TI  - Hydrogen sulfide activates the carotid body chemoreceptors in cat, rabbit and rat
      ex vivo preparations.
AB  - We and others previously reported experimental evidence suggesting an important
      role for hydrogen sulfide (H2S) in oxygen sensing in murine carotid body
      chemoreceptors. More recent data implicated abnormal H2S-mediated chemoreceptor
      signaling in pathological conditions such as chronic heart failure and
      hypertension. However, the idea of H2S as a mediator of oxygen-sensing in
      chemoreceptors has been challenged. In particular, it was shown that exogenous
      H2S inhibited the release of neurotransmitters (ACh and ATP) from the cat carotid
      body, raising the possibility that there exists significant species difference in
      H2S-mediated signaling in chemoreceptors. This study was designed specifically to
      determine the effect of H2S on chemoreceptors in different species. We conducted
      multiunit extracellular recordings of the sinus nerve in the ex vivo carotid body
      preparation taken from the rat, the cat and the rabbit. As observed in the mouse
      carotid body, H2S donors (NaHS or Na2S) evoked qualitatively similar excitatory
      responses of the afferent sinus nerves of the species studied here. The
      excitatory effects of the H2S donors were concentration-dependent and reversible.
      The sinus nerve responses to H2S donors were prevented by blockade of the
      transmission between type I cells and the afferent terminals, as was the response
      to hypoxia. These results demonstrate that exogenous H2S exerts qualitatively
      similar excitatory effects on chemoreceptor afferents of different species. The
      role of endogenous H2S-mediated signaling in carotid body function in different
      species awaits further investigation. 

PMID- 25583662
TI  - Neonatal hyperoxia up regulates cough reflex in young rabbits.
AB  - A link between cough in childhood and neonatal exposure to hyperoxia following
      preterm birth has been suggested. The hypothesis is tested that neonatal exposure
      to hyperoxia is associated with long term up regulation of cough. Airway
      hyperresponsiveness is also investigated because it is a frequent finding in
      children born preterm and may be linked to cough. Thirty nine young rabbits
      survived a 48 h neonatal exposure to 93% oxygen (H, n=26) or continued room air
      (A, n=13). Cough response to mechanical tracheal stimulation and airway responses
      to a mock exercise and to methacholine were studied under anaesthesia. Larger
      incidence of coughs and increased sensitivity to tracheal stimulation occurred in
      H vs A (p<0.01), while bronchial responses to exercise or methacholine were
      similar in both groups. Neonatal hyperoxia is associated with up regulation of
      cough in young rabbits. The lack of a parallel increase in airway responsiveness
      suggests up regulation may be of central origin.

PMID- 25583663
TI  - Bruce Squires Award for microbiome study.

PMID- 25583664
TI  - A 15-year-old rugby player with a head injury.

PMID- 25583665
TI  - Child well-being in Canada: how can we improve on "average"?

PMID- 25583666
TI  - MS trailblazer on the art of medicine.

PMID- 25583668
TI  - 10 health stories that mattered: Jan. 3-9.

PMID- 25583669
TI  - More palliative care specialists is not enough.

PMID- 25583667
TI  - Cost-effectiveness of screening for hepatitis C in Canada.
AB  - BACKGROUND: The seroprevalence of hepatitis C virus (HCV) infection among
      Canadians is estimated at 0.3% to 0.9%. Of those with chronic HCV infection, 10%
      to 20% will experience advanced liver disease by 30 years of infection. Targeted
      screening seems a plausible strategy. We aimed to estimate the health and
      economic effects of various screening and treatment strategies for chronic HCV
      infection in Canada. METHODS: We used a state-transition model to examine the
      cost-effectiveness of 4 screening strategies: no screening; screen and treat with
      pegylated interferon plus ribavarin; screen and treat with pegylated interferon
      and ribavarin-based direct-acting antiviral agents; and screen and treat with
      interferon-free direct-acting antivirals. We considered Canadian residents in 2
      age groups: 25-64 and 45-64 years of age. We obtained model data from the
      literature. We predicted deaths related to chronic HCV infection, costs, quality
      adjusted life-years (QALYs) and incremental cost-effectiveness ratios. RESULTS:
      We found that screening and treating would prevent at least 9 HCV-related deaths
      per 10,000 persons screened over the lifetime of the cohort. Screening was
      associated with QALY increases of 0.0032 to 0.0095 and cost increases of $124 to
      $338 per person, which translated to an incremental cost-effectiveness ratio of
      $34,359 to $44,034 per QALY gained, relative to no screening, depending on age
      group screened and antiviral therapy received. INTERPRETATION: A selective one
      time HCV screening program for people 25-64 or 45-64 years of age in Canada would
      likely be cost-effective. Identification of silent cases of chronic HCV infection
      and the offer of treatment when appropriate could extend the lives of Canadians
      at reasonable cost.

PMID- 25583670
TI  - Giant and multivessel aneurysms of the coronary artery.

PMID- 25583671
TI  - Improving protection for Ebola workers.

PMID- 25583672
TI  - AIDS, activism and access.

PMID- 25583673
TI  - Surgical management for benign paroxysmal positional vertigo of the superior
      semicircular canal.
AB  - Benign paroxysmal positional vertigo of the superior semicircular canal is a rare
      form of BPPV. It accounts for 1% to 3% of cases. The characteristic nystagmus is
      positional, down-beating, with a torsional component elicited by the Dix-Hallpike
      maneuver. Symptoms of superior semicircular canal BPPV often resolve
      spontaneously; however, it can be refractory to repositioning maneuvers. Surgical
      management is described for posterior semicircular canal BPPV. To date, however,
      there is only one reported case of surgical management for superior semicircular
      canal BPPV. Here we show video documentation of positional, down-beating
      nystagmus and describe a case of superior semicircular canal BPPV requiring canal
      occlusion with successful resolution of symptoms.

PMID- 25583675
TI  - Proteomic changes in the brain of the western painted turtle (Chrysemys picta
      bellii) during exposure to anoxia.
AB  - During anoxia, overall protein synthesis is almost undetectable in the brain of
      the western painted turtle. The aim of this investigation was to address the
      question of whether there are alterations to specific proteins by comparing the
      normoxic and anoxic brain proteomes. Reductions in creatine kinase, hexokinase,
      glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase reflected the
      reduced production of adenosine triphosphate (ATP) during anoxia while the
      reduction in transitional endoplasmic reticulum ATPase reflected the conservation
      of ATP or possibly a decrease in intracellular Ca(2+). In terms of neural
      protection programed cell death 6 interacting protein (PDCD6IP; a protein
      associated with apoptosis), dihydropyrimidinase-like protein, t-complex protein,
      and guanine nucleotide protein G(o) subunit alpha (Go alpha; proteins associated
      with neural degradation and impaired cognitive function) also declined. A decline
      in actin, gelsolin, and PDCD6IP, together with an increase in tubulin, also
      provided evidence for the induction of a neurological repair response. Although
      these proteomic alterations show some similarities with the crucian carp (another
      anoxia-tolerant species), there are species-specific responses, which supports
      the theory of no single strategy for anoxia tolerance. These findings also
      suggest the anoxic turtle brain could be an etiological model for investigating
      mammalian hypoxic damage and clinical neurological disorders.

PMID- 25583674
TI  - Aberrant DNA hypermethylation reduces the expression of the desmosome-related
      molecule periplakin in esophageal squamous cell carcinoma.
AB  - Periplakin (PPL), a member of the plakin family of proteins that localizes to
      desmosomes and intermediate filaments, is downregulated in human esophageal
      squamous cell carcinoma (ESCC). Little is known, however, about the molecular
      mechanism underlying the regulation of PPL expression and the contribution of PPL
      loss to the malignant property of the cancer is unclear. We demonstrated that PPL
      mRNA expression was significantly reduced in ESCC tissues compared with that in
      normal tissues. Therefore, we hypothesized that CpG hypermethylation is the cause
      of the downregulation of PPL. Bisulfite-pyrosequencing of 17 cases demonstrated
      that the frequency of PPL methylation was higher in ESCC tissues than in normal
      tissues. When human ESCC cell lines were treated with 5-aza-2'-deoxycytidine (5
      aza-dC), a DNA-methyltransferase inhibitor, PPL transcription was induced. Human
      KYSE270 ESCC cells do not stratify under ordinary culture conditions and rarely
      produce desmosomes; however, the forced expression of PPL promoted cell
      stratification. PPL induction also promoted adhesion to extracellular matrix but
      delayed cell migration. The abundance of desmosome-like structures was greatly
      increased in PPL transfectant as determined by transmission electron microscopy.
      Very low expression of another desmosome protein EVPL in ESCC, even in PPL
      transfectant, also supported the significant role of PPL in desmosome formation
      and cell stratification. Our results first indicate that the downregulation of
      PPL mediated by DNA hypermethylation, which may play an important role in the
      loss of ESCC stratification and likely in metastatic phenotype. 

PMID- 25583676
TI  - Obituary Georg Gerber (1926-2014).

PMID- 25583677
TI  - Biodegradable and bio-based polymers: future prospects of eco-friendly plastics.
AB  - Currently used plastics are mostly produced from petrochemical products, but
      there is a growing demand for eco-friendly plastics. The use of bio-based
      plastics, which are produced from renewable resources, and biodegradable
      plastics, which are degraded in the environment, will lead to a more sustainable
      society and help us solve global environmental and waste management problems. 

PMID- 25583678
TI  - Post-myocardial infarct inflammation and the potential role of cell therapy.
AB  - Myocardial infarction triggers reparative inflammatory processes programmed to
      repair damaged tissue. However, often additional injury to the myocardium occurs
      through the course of this inflammatory process, which ultimately can lead to
      heart failure. The potential beneficial effects of cell therapy in treating
      cardiac ischemic disease, the number one cause of death worldwide, are being
      studied extensively, both in clinical trials using adult stem cells as well as in
      fundamental research on cardiac stem cells and regenerative biology. This review
      summarizes the current knowledge on molecular and cellular processes implicated
      in post-infarction inflammation and discusses the potential beneficial role cell
      therapy might play in this process. Due to its immunomodulatory properties, the
      mesenchymal stromal cell is a candidate to reverse the disease progression of the
      infarcted heart towards heart failure, and therefore is emphasized in this
      review. 

PMID- 25583679
TI  - The Great Recession in Portugal: impact on hospital care use.
AB  - The Great Recession started in Portugal in 2009, coupled with severe austerity.
      This study examines its impact on hospital care utilization, interpreted as
      caused by demand-side effects (related to variations in population income and
      health) and supply-side effects (related to hospitals' tighter budgets and
      reduced capacity). The database included all in-patient stays at all Portuguese
      NHS hospitals over the 2001-2012 period (n=17.7 millions). We analyzed changes in
      discharge rates, casemix index, and length of stay (LOS), using a before-after
      methodology. We additionally measured the association of health care indicators
      to unemployment. A 3.2% higher rate of discharges was observed after 2009. Urgent
      stays increased by 2.5%, while elective in-patient stays decreased by 1.4% after
      2011. The LOS was 2.8% shorter after the crisis onset, essentially driven by the
      4.5% decrease among non-elective stays. A one percentage point increase in
      unemployment rate was associated to a 0.4% increase in total volume, a 2.3%
      decrease in day cases, and a 0.1% decrease in LOS. The increase in total and
      urgent cases may reflect delayed out-patient care and health deterioration; the
      reduced volume of elective stays possibly signal a reduced capacity; finally, the
      shorter stays may indicate either efficiency-enhancing measures or reduced
      quality. 

PMID- 25583680
TI  - Self-catalyzed growth of large-area nanofilms of two-dimensional carbon.
AB  - The graphdiyne (GD), a carbon allotrope with a 2D structure comprising benzene
      rings and carbon-carbon triple bonds, can be synthesized through cross-coupling
      on the surface of copper foil. The key problem is in understanding the dependence
      of layers number and properties, however, the controlled growth of the layers
      numbers of GD film have not been demonstrated, its controlled growth into large
      area and high ordered films with different numbers of layers is still an
      important challenge. Here, we show that a new strategy for synthesizing GD films
      with 2D nanostructures on ZnO nanorod arrays through a combination of reduction
      and a self-catalyzed vapor-liquid-solid growth process, using GD powder as the
      vapor source and ZnO nanorod arrays as the substrate. HRTEM shows the distance
      between pairs of streaks being approximately 0.365 nm by different thicknesses of
      GD films. The approach enables us to construct large-area ordered semiconductive
      films with high-quality surfaces showing high conductivity (up to 2800 S cm(-1)).
      FETs were fabricated based on the well ordered films; we prepared and measured
      over 100 devices. Devices incorporating these well-ordered and highly conductive
      GD films exhibited field-effect mobility as high as 100 cm(2) V(-1) s(-1). 

PMID- 25583681
TI  - Breast cancer: tamoxifen - offering a long-term prevention option.

PMID- 25583682
TI  - Clinical Usefulness of SPECT-CT in Patients with an Unexplained Pain in Metal on
      Metal (MOM) Total Hip Arthroplasty.
AB  - SPECT-CT is increasingly used to assess painful knee arthroplasties. The aim of
      this study was to evaluate the clinical usefulness of SPECT-CT in unexplained
      painful MOM hip arthroplasty. We compared the diagnosis and management plan for
      19 prosthetic MOM hips in 15 subjects with unexplained pain before and after
      SPECT-CT. SPECT-CT changed the management decision in 13 (68%) subjects, Chi
      Square=5.49, P=0.24. In 6 subjects (32%) pain remained unexplained however the
      result reassured the surgeon to continue with non-operative management. SPECT-CT
      should be reserved as a specialist test to help identify possible causes of pain
      where conventional investigations have failed. It can help reassure surgeons
      making management decisions for patients with unexplained pain following MOM hip
      arthroplasty. 

PMID- 25583683
TI  - Total joint arthroplasty in cancer patients.
AB  - Increasing numbers of total joint arthroplasty (TJA) patients have a history, or
      an active diagnosis, of cancer. We aimed to evaluate the risk of early
      postoperative complications in these patients. In our series, a history of
      malignancy was associated with an elevated risk of ischemic cardiac events and
      postoperative deep vein thrombosis (DVT), while active malignancy was associated
      with increased respiratory and renal complications, hematoma/seroma formation and
      early postoperative mortality. Both groups presented increased rates of overall
      in-hospital complications. Patients with bone metastasis to the hip demonstrated
      increased DVT and 90-day mortality rates. Cancer patients have increased
      morbidity and mortality after TJA and should undergo comprehensive medical
      optimization and adapted thromboprophylaxis. 

PMID- 25583684
TI  - Response Letter to Editor In Reference to Letter to Editor about "Adverse
      Clinical Outcomes in a Primary Modular Neck/Stem System".

PMID- 25583685
TI  - Relaxation of ferroelectric thin films of diisopropylammonium perchlorate.
AB  - Molecular ferroelectric thin films are highly desirable for their easy and
      environmentally friendly processing, light weight, and mechanical flexibility. A
      thin film of diisopropylammonium perchlorate (DIPAP) processed by a spin-coating
      method shows a good roughness and textured structure with (101) orientation in
      the ferroelectric phase with a space group of P1. Simultaneously, the thin film
      shows ferroelectricity and ferroelectric relaxivity above room temperature, which
      is completely different from crystals. These properties make DIPAP a candidate in
      sensing, data storage, electro-optics, and molecular/flexible electronics. 

PMID- 25583686
TI  - Discrimination of non-melanoma skin lesions from non-tumor human skin tissues in
      vivo using Raman spectroscopy and multivariate statistics.
AB  - BACKGROUND AND OBJECTIVE: Raman spectroscopy was used to discriminate human non
      melanoma skin lesions from non-tumor tissues in vivo. This work proposed the
      discrimination between non-melanoma (basal cell carcinoma, BCC; squamous cell
      carcinoma, SCC) and pre-cancerous lesions (actinic keratosis, AK) from benign
      lesions and normal (non-tumor group, NT) tissues, using near-infrared Raman
      spectroscopy with a Raman probe. MATERIALS AND METHODS: Prior to surgery, the
      spectra of suspicious lesions were obtained in situ. The spectra of adjacent,
      clinically normal skin were also obtained. Lesions were resectioned and submitted
      for histopathology. The Raman spectra were measured using a Raman spectrometer
      (830 nm). Two types of discrimination models were developed to distinguish the
      different histopathological groups. The principal components analysis
      discriminant analysis (PCA/DA) and the partial least squares discriminant
      analysis (PLS/DA) were based on Euclidean, quadratic and Mahalanobis distances.
      RESULTS: PCA and PLS spectral vectors showed spectral features of skin
      constituents, such as lipids (between 1,250 cm(-1) and 1,300 cm(-1) and at 1,450
      cm(-1)) and proteins (between 870 cm(-1) and 940 cm(-1), 1,240 cm(-1) and 1,271
      cm(-1), and at 1,000 cm(-1) and 1,450 cm(-1)). Despite the small spectral
      differences between malignant lesions and benign tissues, the algorithms
      discriminated the spectra of non-melanoma skin and pre-cancerous lesions from
      benign and normal tissues, with an overall accuracy of 82.8% and 91.9%,
      respectively. CONCLUSION: PCA and PLS could discriminate Raman spectra of skin
      tissues, opening the way for an in vivo optical diagnosis.

PMID- 25583687
TI  - Mapping the future: towards oncology curriculum reform in undergraduate medical
      education at a Canadian medical school.
AB  - PURPOSE: To evaluate (1) the quantity and quality of current undergraduate
      oncology teaching at a major Canadian medical school; and (2) curricular changes
      over the past decade, to enhance local oncology education and provide insight for
      other educators. METHODS AND MATERIALS: Relevant 2011-2012 undergraduate
      curricular sessions were extracted from the University of Toronto curriculum
      mapping database using keywords and database identifiers. Educational sessions
      were analyzed according to Medical Council of Canada objectives, discussion
      topics, instructor qualifications, teaching format, program year, and course
      subject. Course-related oncology research projects performed by students during
      2000 to 2012 were extracted from another internal database. Elective choices of
      clerks during 2008-2014 were retrieved from the institution. The 2011-2012 and
      2000-2001 curricula were compared using common criteria. RESULTS: The 2011-2012
      curriculum covers 5 major themes (public health, cancer biology, diagnosis,
      principles of care, and therapy), which highlight 286 oncology teaching topics
      within 80 sessions. Genitourinary (10, 12.5%), gynecologic (8, 10.0%), and
      gastrointestinal cancers (7.9, 9.8%) were the most commonly taught cancers. A
      minority of sessions were taught by surgical oncologists (6.5, 8.1%), medical
      oncologists (2.5, 3.1%), and radiation oncologists (1, 1.2%). During 2000-2012,
      9.0% of students (233 of 2578) opted to complete an oncology research project.
      During 2008-2014, oncology electives constituted 2.2% of all clerkship elective
      choices (209 of 9596). Compared with pre-2001 curricula, the 2012 oncology
      curriculum shows notable expansion in the coverage of epidemiology (6:1
      increase), prevention (4:1), screening (3:1), and molecular biology (6:1).
      CONCLUSIONS: The scope of the oncology curriculum has grown over the past decade.
      Nevertheless, further work is needed to improve medical student knowledge of
      cancers, particularly those relevant to public health needs. Defining minimum
      curricular content, emphasizing content based on population needs, and ensuring
      educational delivery with the support and expertise of oncologists and non
      oncologists will be essential next steps.

PMID- 25583688
TI  - Remote rearrangement of the metal center in a (eta6-C6Me6)Ru(II) complex.
AB  - Reaction of [(eta(6)-C6Me6)RuCl(Ph)(PMe3)] with internal alkynes in the presence
      of NaBAr(F)4 gave rise to the 1,4-Ru migration to form the o-vinylaryl complex,
      providing the first example of 1,4-metal migration of a group 8 metal center; in
      one case further isomerization to an eta(3)-allyl complex was observed. 

PMID- 25583692
TI  - Funding allocations for patients across England are far from fair, says MPs'
      report.

PMID- 25583693
TI  - Real-time monitoring of phosphorylation kinetics with self-assembled nano
      oscillators.
AB  - Phosphorylation is a post-translational modification that is involved in many
      basic cellular processes and diseases, but is difficult to detect in real time
      with existing technologies. A label-free detection of phosphorylation is reported
      in real time with self-assembled nano-oscillators. Each nano-oscillator consists
      of a gold nanoparticle tethered to a gold surface with a molecular linker. When
      the nanoparticle is charged, the nano-oscillator can be driven into oscillation
      with an electric field and detected with a plasmonic imaging approach. The nano
      oscillators measure charge change associated with phosphorylation of peptides
      attached onto a single nanoparticle, allowing us to study the dynamic process of
      phosphorylation in real time without antibodies down to a few molecules, from
      which Michaelis and catalytic rate constants are determined. 

PMID- 25583696
TI  - Diabetes: Elevated risk of mortality in type 1 diabetes mellitus.

PMID- 25583698
TI  - Statin therapy for skeletal dysplasia.

PMID- 25583701
TI  - Cancer survivors report array of unmet needs many years after diagnosis.

PMID- 25583694
TI  - Chronic fluoxetine increases extra-hippocampal neurogenesis in adult mice.
AB  - BACKGROUND: Chronic treatment with antidepressants has been shown to enhance
      neurogenesis in the adult mammalian brain. Although this effect was initially
      reported to be restricted to the hippocampus, recent work has suggested that
      fluoxetine, a selective serotonin reuptake inhibitor, also promotes neurogenesis
      in the cortex. However, whether antidepressants target neural progenitor cells in
      other brain regions has not been examined. METHODS: Here, we used BrdU labeling
      and immunohistochemistry with a transgenic mouse line in which nestin+ neural
      progenitor cells can be inducibly labeled with the fluorescent protein, Tomato,
      following tamoxifen administration. We investigated the effects of chronic
      fluoxetine on cell proliferation and nestin+ progenitor cells in periventricular
      areas in the medial hypothalamus and medial habenula, two brain areas involved in
      stress and anxiety responses. RESULTS: Our data provide the first in vivo
      evidence that fluoxetine promotes cell proliferation and neurogenesis and
      increases the mRNA levels of BDNF in the hypothalamus and habenula. CONCLUSIONS:
      By identifying novel cellular targets of fluoxetine, our results may provide new
      insight into the mechanisms underlying antidepressant responses.

PMID- 25583703
TI  - Millions of Americans would drop insurance if exchange subsidies didn't exist,
      studies find.

PMID- 25583704
TI  - What is the best glomerular filtration marker to identify people with chronic
      kidney disease most likely to have poor outcomes?

PMID- 25583702
TI  - What are incident reports telling us? A comparative study at two Australian
      hospitals of medication errors identified at audit, detected by staff and
      reported to an incident system.
AB  - OBJECTIVES: To (i) compare medication errors identified at audit and observation
      with medication incident reports; (ii) identify differences between two hospitals
      in incident report frequency and medication error rates; (iii) identify
      prescribing error detection rates by staff. DESIGN: Audit of 3291 patient records
      at two hospitals to identify prescribing errors and evidence of their detection
      by staff. Medication administration errors were identified from a direct
      observational study of 180 nurses administering 7451 medications. Severity of
      errors was classified. Those likely to lead to patient harm were categorized as
      'clinically important'. SETTING: Two major academic teaching hospitals in Sydney,
      Australia. MAIN OUTCOME MEASURES: Rates of medication errors identified from
      audit and from direct observation were compared with reported medication incident
      reports. RESULTS: A total of 12 567 prescribing errors were identified at audit.
      Of these 1.2/1000 errors (95% CI: 0.6-1.8) had incident reports. Clinically
      important prescribing errors (n = 539) were detected by staff at a rate of
      218.9/1000 (95% CI: 184.0-253.8), but only 13.0/1000 (95% CI: 3.4-22.5) were
      reported. 78.1% (n = 421) of clinically important prescribing errors were not
      detected. A total of 2043 drug administrations (27.4%; 95% CI: 26.4-28.4%)
      contained >= 1 errors; none had an incident report. Hospital A had a higher
      frequency of incident reports than Hospital B, but a lower rate of errors at
      audit. CONCLUSIONS: Prescribing errors with the potential to cause harm
      frequently go undetected. Reported incidents do not reflect the profile of
      medication errors which occur in hospitals or the underlying rates. This
      demonstrates the inaccuracy of using incident frequency to compare patient risk
      or quality performance within or across hospitals. New approaches including data
      mining of electronic clinical information systems are required to support more
      effective medication error detection and mitigation.

PMID- 25583705
TI  - Thinking style changes among deaf, hard-of-hearing, and hearing students.
AB  - This study explores how university students' thinking styles changed over a
      single academic year by twice administering the Thinking Styles Inventory-Revised
      II to 256 deaf or hard-of-hearing (DHH) students and 286 hearing students from
      art and design academic disciplines in China. Results showed that after having
      studied at the university for one academic year, hearing students showed
      increased use of Type I thinking styles (more creativity generated, less
      structured, and more complex) and less use of Type II thinking styles (more norm
      favoring, more structured, and more simplistic), whereas DHH students
      demonstrated increased use of both Type I and Type II thinking styles. Moreover,
      students' changes in thinking styles differed across university class levels. The
      contributions, limitations, and implications of the present research are
      discussed.

PMID- 25583706
TI  - Concept formation skills in long-term cochlear implant users.
AB  - This study investigated if a period of auditory sensory deprivation followed by
      degraded auditory input and related language delays affects visual concept
      formation skills in long-term prelingually deaf cochlear implant (CI) users. We
      also examined if concept formation skills are mediated or moderated by other
      neurocognitive domains (i.e., language, working memory, and executive control).
      Relative to normally hearing (NH) peers, CI users displayed significantly poorer
      performance in several specific areas of concept formation, especially when
      multiple comparisons and relational concepts were components of the task.
      Differences in concept formation between CI users and NH peers were fully
      explained by differences in language and inhibition-concentration skills.
      Language skills were also found to be more strongly related to concept formation
      in CI users than in NH peers. The present findings suggest that complex
      relational concepts may be adversely affected by a period of early prelingual
      deafness followed by access to underspecified and degraded sound patterns and
      spoken language transmitted by a CI. Investigating a unique clinical population
      such as early-implanted prelingually deaf children with CIs can provide new
      insights into foundational brain-behavior relations and developmental processes.

PMID- 25583707
TI  - Comparisons of social competence in young children with and without hearing loss:
      a dynamic systems framework.
AB  - This study compared levels of social competence and language development in 74
      young children with hearing loss and 38 hearing peers aged 2.5-5.3 years. This
      study was the first to examine the relationship between oral language and social
      competence using a dynamic systems framework in children with and without hearing
      loss. We hypothesized that, due to deficits in oral language, children who were
      deaf would display lower levels of social competence than their hearing peers.
      Furthermore, language age would predict social competence scores. Social
      competence was measured with a general and deaf-specific measure. Results showed
      that children with hearing loss performed significantly worse than hearing peers
      on the general measure but better than the norms on the deaf-specific measure.
      Controlling for maternal education and income, regression analyses indicated that
      hearing status and language age predicted social competence in both groups. Among
      children with hearing loss, correlations were also found between age at
      diagnosis, age at amplification, and two of the general social competence
      measures. Results supported our hypothesis that deficits in language would have
      cascading negative effects on the development of social competence in young deaf
      children. Development of early intervention programs that target both language
      and social skills are needed for this population. 

PMID- 25583708
TI  - With or without semantic mediation: retrieval of lexical representations in sign
      production.
AB  - How are lexical representations retrieved during sign production? Similar to
      spoken languages, lexical representation in sign language must be accessed
      through semantics when naming pictures. However, it remains an open issue whether
      lexical representations in sign language can be accessed via routes that bypass
      semantics when retrieval is elicited by written words. Here we address this issue
      by exploring under which circumstances sign retrieval is sensitive to semantic
      context. To this end we replicate in sign language production the cumulative
      semantic cost: The observation that naming latencies increase monotonically with
      each additional within-category item that is named in a sequence of pictures. In
      the experiment reported here, deaf participants signed sequences of pictures or
      signed sequences of Italian written words using Italian Sign Language. The
      results showed a cumulative semantic cost in picture naming but, strikingly, not
      in word naming. This suggests that only picture naming required access to
      semantics, whereas deaf signers accessed the sign language lexicon directly
      (i.e., bypassing semantics) when naming written words. The implications of these
      findings for the architecture of the sign production system are discussed in the
      context of current models of lexical access in spoken language production. 

PMID- 25583709
TI  - Insights into the mechanism of inhibition of CXCR4: identification of
      Piperidinylethanamine analogs as anti-HIV-1 inhibitors.
AB  - The cellular entry of HIV-1 into CD4(+) T cells requires ordered interactions of
      HIV-1 envelope glycoprotein with C-X-C chemokine receptor type 4 (CXCR4)
      receptors. However, such interactions, which should be critical for rational
      structure-based discovery of new CXCR4 inhibitors, remain poorly understood. Here
      we first determined the effects of amino acid substitutions in CXCR4 on HIV-1NL 4
      - 3 glycoprotein-elicited fusion events using site-directed mutagenesis-based
      fusion assays and identified 11 potentially key amino acid substitutions,
      including D97A and E288A, which caused >30% reductions in fusion. We subsequently
      carried out a computational search of a screening library containing ~604,000
      compounds, in order to identify potential CXCR4 inhibitors. The computational
      search used the shape of IT1t, a known CXCR4 inhibitor, as a reference and
      employed various algorithms, including shape similarity, isomer generation, and
      docking against a CXCR4 crystal structure. Sixteen small molecules were
      identified for biological assays based on their high shape similarity to IT1t,
      and their putative binding modes formed hydrogen bond interactions with the amino
      acids identified above. Three compounds with piperidinylethanamine cores showed
      activity and were resynthesized. One molecule, designated CX6, was shown to
      significantly inhibit fusion elicited by X4 HIV-1NL 4 - 3 glycoprotein (50%
      inhibitory concentration [IC50], 1.9 MUM), to inhibit Ca(2+) flux elicited by
      stromal cell-derived factor 1alpha (SDF-1alpha) (IC50, 92 nM), and to exert anti
      HIV-1 activity (IC50, 1.5 MUM). Structural modeling demonstrated that CX6 bound
      to CXCR4 through hydrogen bond interactions with Asp97 and Glu288. Our study
      suggests that targeting CXCR4 residues important for fusion elicited by HIV-1
      envelope glycoprotein should be a useful and feasible approach to identifying
      novel CXCR4 inhibitors, and it provides important insights into the mechanism by
      which small-molecule CXCR4 inhibitors exert their anti-HIV-1 activities. 

PMID- 25583710
TI  - Whole-genome sequence of Chryseobacterium oranimense, a colistin-resistant
      bacterium isolated from a cystic fibrosis patient in France.
AB  - For the first time, we report the whole-genome sequence analysis of
      Chryseobacterium oranimense G311, a multidrug-resistant bacterium, from a cystic
      fibrosis patient in France, including resistance to colistin. Whole-genome
      sequencing of C. oranimense G311 was performed using Ion Torrent PGM, and RAST,
      the EMBL-EBI server, and the Antibiotic Resistance Gene-ANNOTation (ARG-ANNOT)
      database were used for annotation of all genes, including antibiotic resistance
      (AR) genes. General features of the C. oranimense G311 draft genome were compared
      to the other available genomes of Chryseobacterium gleum and Chryseobacterium sp.
      strain CF314. C. oranimense G311 was found to be resistant to all beta-lactams,
      including imipenem, and to colistin. The genome size of C. oranimense G311 is
      4,457,049 bp in length, with 37.70% GC content. We found 27 AR genes in the
      genome, including beta-lactamase genes which showed little similarity to the
      known beta-lactamase genes and could likely be novel. We found the type I
      polyketide synthase operon followed by a zeaxanthin glycosyltransferase gene in
      the genome, which could impart the yellow pigmentation of the isolate. We located
      the O-antigen biosynthesis cluster, and we also discovered a novel capsular
      polysaccharide biosynthesis cluster. We also found known mutations in the
      orthologs of the pmrA (E8D), pmrB (L208F and P360Q), and lpxA (G68D) genes. We
      speculate that the presence of the capsular cluster and mutations in these genes
      could explain the resistance of this bacterium to colistin. We demonstrate that
      whole-genome sequencing was successfully applied to decipher the resistome of a
      multidrug resistance bacterium associated with cystic fibrosis patients. 

PMID- 25583711
TI  - Sublethal concentrations of carbapenems alter cell morphology and genomic
      expression of Klebsiella pneumoniae biofilms.
AB  - Klebsiella pneumoniae, a Gram-negative bacterium, is normally associated with
      pneumonia in patients with weakened immune systems. However, it is also a
      prevalent nosocomial infectious agent that can be found in infected surgical
      sites and combat wounds. Many of these clinical strains display multidrug
      resistance. We have worked with a clinical strain of K. pneumoniae that was
      initially isolated from a wound of an injured soldier. This strain demonstrated
      resistance to many commonly used antibiotics but sensitivity to carbapenems. This
      isolate was capable of forming biofilms in vitro, contributing to its increased
      antibiotic resistance and impaired clearance. We were interested in determining
      how sublethal concentrations of carbapenem treatment specifically affect K.
      pneumoniae biofilms both in morphology and in genomic expression. Scanning
      electron microscopy showed striking morphological differences between untreated
      and treated biofilms, including rounding, blebbing, and dimpling of treated
      cells. Comparative transcriptome analysis using RNA sequencing (RNA-Seq)
      technology identified a large number of open reading frames (ORFs) differentially
      regulated in response to carbapenem treatment at 2 and 24 h. ORFs upregulated
      with carbapenem treatment included genes involved in resistance, as well as those
      coding for antiporters and autoinducers. ORFs downregulated included those coding
      for metal transporters, membrane biosynthesis proteins, and motility proteins.
      Quantitative real-time PCR validated the general trend of some of these
      differentially regulated ORFs. Treatment of K. pneumoniae biofilms with sublethal
      concentrations of carbapenems induced a wide range of phenotypic and gene
      expression changes. This study reveals some of the mechanisms underlying how
      sublethal amounts of carbapenems could affect the overall fitness and pathogenic
      potential of K. pneumoniae biofilm cells. 

PMID- 25583712
TI  - Phenotypic and genotypic characterization of pyrazinamide resistance among
      multidrug-resistant Mycobacterium tuberculosis isolates in Zhejiang, China.
AB  - To explore the phenotypic and genotypic characterization of pyrazinamide (PZA)
      resistance among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates
      in Zhejiang province, a total of 274 MDR-TB isolates were collected. Drug
      susceptibility testing and spoligotyping were performed on all clinical isolates.
      In addition, the mutated features of PZA-resistant loci, including pncA and rpsA,
      were also analyzed by DNA sequencing. Our results showed that the prevalence of
      PZA resistance among MDR-TB strains in Zhejiang province was 43.07% and that PZA
      resistance was associated with concomitant resistance to streptomycin. The
      majority of PZA-resistant MDR-TB isolates belonged to the Beijing family.
      Mutations within pncA, not rpsA, constituted the primary mechanism of PZA
      resistance. Among 118 PZA-resistant isolates, 53 different mutations were
      observed in pncA, and most of them were point mutations. Compared with the
      phenotypic data, DNA sequencing of pncA has sensitivity and specificity of 77.97%
      and 96.79%, respectively. Analysis of pncA provided a robust tool for rapid
      detection of PZA drug resistance. 

PMID- 25583713
TI  - Insect-derived cecropins display activity against Acinetobacter baumannii in a
      whole-animal high-throughput Caenorhabditis elegans model.
AB  - The rise of multidrug-resistant Acinetobacter baumannii and a concomitant
      decrease in antibiotic treatment options warrants a search for new classes of
      antibacterial agents. We have found that A. baumannii is pathogenic and lethal to
      the model host organism Caenorhabditis elegans and have exploited this phenomenon
      to develop an automated, high-throughput, high-content screening assay in liquid
      culture that can be used to identify novel antibiotics effective against A.
      baumannii. The screening assay involves coincubating C. elegans with A. baumannii
      in 384-well plates containing potential antibacterial compounds. At the end of
      the incubation period, worms are stained with a dye that stains only dead
      animals, and images are acquired using automated microscopy and then analyzed
      using an automated image analysis program. This robust assay yields a Z' factor
      consistently greater than 0.7. In a pilot experiment to test the efficacy of the
      assay, we screened a small custom library of synthetic antimicrobial peptides
      (AMPs) that were synthesized using publicly available sequence data and/or
      transcriptomic data from immune-challenged insects. We identified cecropin A and
      14 other cecropin or cecropin-like peptides that were able to enhance C. elegans
      survival in the presence of A. baumannii. Interestingly, one particular hit,
      BR003-cecropin A, a cationic peptide synthesized by the mosquito Aedes aegypti,
      showed antibiotic activity against a panel of Gram-negative bacteria and
      exhibited a low MIC (5 MUg/ml) against A. baumannii. BR003-cecropin A causes
      membrane permeability in A. baumannii, which could be the underlying mechanism of
      its lethality. 

PMID- 25583715
TI  - Molecular characterization of the cytochrome b gene and in vitro atovaquone
      susceptibility of Plasmodium falciparum isolates from Kenya.
AB  - The prevalence of a genetic polymorphism(s) at codon 268 in the cytochrome b
      gene, which is associated with failure of atovaquone-proguanil treatment, was
      analyzed in 227 Plasmodium falciparum parasites from western Kenya. The
      prevalence of the wild-type allele was 63%, and that of the Y268S (denoting a Y
      to-S change at position 268) mutant allele was 2%. There were no pure Y268C or
      Y268N mutant alleles, only mixtures of a mutant allele(s) with the wild type.
      There was a correlation between parasite 50% inhibitory concentration (IC50) and
      parasite genetic polymorphism; mutant alleles had higher IC50s than the wild
      type. 

PMID- 25583716
TI  - The strength of synergistic interaction between posaconazole and caspofungin
      depends on the underlying azole resistance mechanism of Aspergillus fumigatus.
AB  - The majority of azole resistance mechanisms in Aspergillus fumigatus correspond
      to mutations in the cyp51A gene. As azoles are less effective against infections
      caused by multiply azole-resistant A. fumigatus isolates, new therapeutic options
      are warranted for treating these infections. We therefore investigated the in
      vitro combination of posaconazole (POSA) and caspofungin (CAS) against 20 wild
      type and resistant A. fumigatus isolates with 10 different resistance mechanisms.
      Fungal growth was assessed with the XTT [2,3-bis (2-methoxy-4-nitro-5
      sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt] method. Pharmacodynamic
      interactions were assessed with the fractional inhibitory concentration (FIC)
      index (FICi) on the basis of 10% (FICi-0), 25% (FICi-1), or 53 0% (FICi-2)
      growth, and FICs were correlated with POSA and CAS concentrations. Synergy and
      antagonism were concluded when the FICi values were statistically significantly
      (t test, P < 0.05) lower than 1 and higher than 1.25, respectively. Significant
      synergy was found for all isolates with mean FICi-0 values ranging from 0.28 to
      0.75 (median, 0.46). Stronger synergistic interactions were found with FICi-1
      (median, 0.18; range, 0.07 to 0.47) and FICi-2 (0.31; 0.07 to 0.6). The FICi-2
      values of isolates with tandem-repeat-containing mutations or codon M220 were
      lower than those seen with the other isolates (P < 0.01). FIC-2 values were
      inversely correlated with POSA MICs (rs = -0.52, P = 0.0006) and linearly with
      the ratio of drug concentrations in combination over the MIC of POSA (rs = 0.76,
      P < 0.0001) and CAS (rs = 0.52, P = 0.0004). The synergistic effect of the
      combination of POSA and CAS (POSA/CAS) against A. fumigatus isolates depended on
      the underlying azole resistance mechanism. Moreover, the drug combination synergy
      was found to be increased against isolates with elevated POSA MICs compared to
      wild-type isolates. 

PMID- 25583714
TI  - Multicenter evaluation of MIC distributions for epidemiologic cutoff value
      definition to detect amphotericin B, posaconazole, and itraconazole resistance
      among the most clinically relevant species of Mucorales.
AB  - Clinical breakpoints (CBPs) have not been established for the Mucorales and any
      antifungal agent. In lieu of CBPs, epidemiologic cutoff values (ECVs) are
      proposed for amphotericin B, posaconazole, and itraconazole and four Mucorales
      species. Wild-type (WT) MIC distributions (organisms in a species-drug
      combination with no detectable acquired resistance mechanisms) were defined with
      available pooled CLSI MICs from 14 laboratories (Argentina, Australia, Canada,
      Europe, India, Mexico, and the United States) as follows: 10 Apophysomyces
      variabilis, 32 Cunninghamella bertholletiae, 136 Lichtheimia corymbifera, 10
      Mucor indicus, 123 M. circinelloides, 19 M. ramosissimus, 349 Rhizopus arrhizus,
      146 R. microsporus, 33 Rhizomucor pusillus, and 36 Syncephalastrum racemosum
      isolates. CLSI broth microdilution MICs were aggregated for the analyses. ECVs
      comprising >=95% and >=97.5% of the modeled populations were as follows:
      amphotericin B ECVs for L. corymbifera were 1 and 2 MUg/ml, those for M.
      circinelloides were 1 and 2 MUg/ml, those for R. arrhizus were 2 and 4 MUg/ml,
      and those for R. microsporus were 2 and 2 MUg/ml, respectively; posaconazole ECVs
      for L. corymbifera were 1 and 2, those for M. circinelloides were 4 and 4, those
      for R. arrhizus were 1 and 2, and those for R. microsporus were 1 and 2,
      respectively; both itraconazole ECVs for R. arrhizus were 2 MUg/ml. ECVs may aid
      in detecting emerging resistance or isolates with reduced susceptibility (non-WT
      MICs) to the agents evaluated. 

PMID- 25583717
TI  - In vitro spectrum of pexiganan activity when tested against pathogens from
      diabetic foot infections and with selected resistance mechanisms.
AB  - Pexiganan, a 22-amino-acid synthetic cationic peptide, is currently in phase 3
      clinical trials as a topical antimicrobial agent for the treatment of mild
      infections associated with diabetic foot ulcers. Bacterial isolates from the 2013
      SENTRY Antimicrobial Surveillance Program designated as pathogens from diabetic
      foot infections (DFI) and Gram-negative and -positive pathogens from various
      infection types that harbored selected resistance mechanisms/phenotypes were
      tested against pexiganan in reference cation-adjusted Mueller-Hinton broth. The
      MIC50 and MIC90 against all organisms tested from DFI were 16 and 32 MUg/ml,
      respectively. Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri,
      Enterobacter cloacae, Acinetobacter species, and Pseudomonas aeruginosa MIC
      values ranged from 8 to 16 MUg/ml. Pexiganan MIC values among Staphylococcus
      aureus (methicillin-resistant S. aureus [MRSA] and methicillin-susceptible S.
      aureus [MSSA]), beta-hemolytic streptococci, and Enterococcus faecium ranged from
      8 to 32 MUg/ml. Pexiganan activity was not adversely affected for members of the
      family Enterobacteriaceae or P. aeruginosa that produced beta-lactamases or
      resistance mechanisms to other commonly used antimicrobial agents. Decreased
      susceptibility to vancomycin did not affect pexiganan activity against S. aureus
      or E. faecium. Enterococcus faecalis appears to be intrinsically less susceptible
      to pexiganan (MIC, 32 to 256 MUg/ml). The "all organism" MIC90 of 32 MUg/ml for
      pexiganan in this study was >250-fold below the pexiganan concentration in the
      cream/delivery vehicle being developed for topical use. 

PMID- 25583718
TI  - Amdinocillin (Mecillinam) resistance mutations in clinical isolates and
      laboratory-selected mutants of Escherichia coli.
AB  - Amdinocillin (mecillinam) is a beta-lactam antibiotic that is used mainly for the
      treatment of uncomplicated urinary tract infections. The objectives of this study
      were to identify mutations that confer amdinocillin resistance on laboratory
      isolated mutants and clinical isolates of Escherichia coli and to determine why
      amdinocillin resistance remains rare clinically even though resistance is easily
      selected in the laboratory. Under laboratory selection, frequencies of mutation
      to amdinocillin resistance varied from 8 * 10(-8) to 2 * 10(-5) per cell,
      depending on the concentration of amdinocillin used during selection. Several
      genes have been demonstrated to give amdinocillin resistance, but here eight
      novel genes previously unknown to be involved in amdinocillin resistance were
      identified. These genes encode functions involved in the respiratory chain, the
      ribosome, cysteine biosynthesis, tRNA synthesis, and pyrophosphate metabolism.
      The clinical isolates exhibited significantly greater fitness than the laboratory
      isolated mutants and a different mutation spectrum. The cysB gene was mutated
      (inactivated) in all of the clinical isolates, in contrast to the laboratory
      isolated mutants, where mainly other types of more costly mutations were found.
      Our results suggest that the frequency of mutation to amdinocillin resistance is
      high because of the large mutational target (at least 38 genes). However, the
      majority of these resistant mutants have a low growth rate, reducing the
      probability that they are stably maintained in the bladder. Inactivation of the
      cysB gene and a resulting loss of cysteine biosynthesis are the major mechanism
      of amdinocillin resistance in clinical isolates of E. coli. 

PMID- 25583719
TI  - Molecular and biochemical characterization of CTX-M-131, a natural Asp240Gly
      variant derived from CTX-M-2, produced by a Providencia rettgeri clinical strain
      in Sao Paulo, Brazil.
AB  - CTX-M-131 is a natural Asp240Gly variant from the CTX-M-2 group detected in a
      Providencia rettgeri clinical strain from Brazil. Molecular analysis showed that
      blaCTX-M-131 was inserted in a complex class 1 integron harbored by a 112-kb
      plasmid, which has not been previously described as a platform for CTX-M-encoding
      genes with the Asp240Gly mutation. Steady-state kinetic parameters showed that
      the enzyme has a typical cefotaximase catalytic profile and an enhanced activity
      against ceftazidime. 

PMID- 25583720
TI  - In vitro antibiotic susceptibilities of Yersinia pestis determined by broth
      microdilution following CLSI methods.
AB  - In vitro susceptibilities to 45 antibiotics were determined for 30 genetically
      and geographically diverse strains of Yersinia pestis by the broth microdilution
      method at two temperatures, 28 degrees C and 35 degrees C, following Clinical and
      Laboratory Standards Institute (CLSI) methods. The Y. pestis strains demonstrated
      susceptibility to aminoglycosides, quinolones, tetracyclines, beta-lactams,
      cephalosporins, and carbapenems. Only a 1-well shift was observed for the
      majority of antibiotics between the two temperatures. Establishing and comparing
      antibiotic susceptibilities of a diverse but specific set of Y. pestis strains by
      standardized methods and establishing population ranges and MIC50 and MIC90
      values provide reference information for assessing new antibiotic agents and also
      provide a baseline for use in monitoring any future emergence of resistance. 

PMID- 25583721
TI  - Simian-tropic HIV as a model to study drug resistance against integrase
      inhibitors.
AB  - Drug resistance represents a key aspect of human immunodeficiency virus (HIV)
      treatment failure. It is important to develop nonhuman primate models for
      studying issues of drug resistance and the persistence and transmission of drug
      resistant viruses. However, relatively little work has been conducted using
      either simian immunodeficiency virus (SIV) or SIV/HIV recombinant viruses for
      studying resistance against integrase strand transfer inhibitors (INSTIs). Here,
      we used a T-cell-tropic SIV/HIV recombinant virus in which the capsid and vif
      regions of HIV-1 were replaced with their SIV counterparts (simian-tropic HIV-1
      [stHIV-1](SCA,SVIF)) to study the impact of a number of drug resistance
      substitutions in the integrase coding region at positions E92Q, G118R, E138K,
      Y143R, S153Y, N155H, and R263K on drug resistance, viral infectivity, and viral
      replication capacity. Our results show that each of these substitutions exerted
      effects that were similar to their effects in HIV-1. Substitutions associated
      with primary resistance against dolutegravir were more detrimental to stHIV
      1(SCA,SVIF) infectiousness than were resistance substitutions associated with
      raltegravir and elvitegravir, consistent with data that have been reported for
      HIV-1. These findings support the role of stHIV-1(SCA,SVIF) as a useful model
      with which to evaluate the role of INSTI resistance substitutions on viral
      persistence, transmissibility, and pathogenesis in a nonhuman primate model. 

PMID- 25583722
TI  - Impact of extended-spectrum beta-lactamase production on treatment outcomes of
      acute pyelonephritis caused by escherichia coli in patients without health care
      associated risk factors.
AB  - Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) is
      increasingly identified as a cause of acute pyelonephritis (APN) among patients
      without recent health care contact, i.e., community-associated APN. This case
      control study compared 75 cases of community-associated ESBL-EC APN (CA-ESBL) to
      225 controls of community-associated non-ESBL-EC APN (CA-non-ESBL) to identify
      the risk factors for ESBL-EC acquisition and investigate the impact of ESBL on
      the treatment outcomes of community-associated APN (CA-APN) caused by E. coli at
      a Korean hospital during 2007 to 2013. The baseline characteristics were similar
      between the cases and controls; the risk factors for ESBL-EC were age (>55
      years), antibiotic use within the previous year, and diabetes with recurrent APN.
      The severity of illness did not differ between CA-ESBL and CA-non-ESBL (Acute
      Physiology and Chronic Health Evaluation [APACHE] II scores [mean +/- standard
      deviation], 7.7 +/- 5.9 versus 6.4 +/- 5.3; P = 0.071). The proportions of
      clinical (odds ratio [OR], 1.76; 95% confidence interval [CI], 0.57 to 5.38; P =
      0.323) and microbiological (OR, 1.16; 95% CI, 0.51 to 2.65; P = 0.730) cures were
      similar, although the CA-ESBL APN patients were less likely to receive
      appropriate antibiotics within 48 h. A multivariable Cox proportional hazards
      analysis of the prognostic factors for CA-APN caused by E. coli showed that ESBL
      production was not a significant factor for clinical (hazard ratio [HR], 0.39;
      95% CI, 0.12 to 1.30; P = 0.126) or microbiological (HR, 0.49; 95% CI, 0.21 to
      1.12; P = 0.091) failure. The estimates did not change after incorporating
      weights calculated using propensity scores for acquiring ESBL-EC. Therefore, ESBL
      production did not negatively affect treatment outcomes among patients with
      community-associated E. coli APN. 

PMID- 25583724
TI  - Missense mutations in PBP2A Affecting ceftaroline susceptibility detected in
      epidemic hospital-acquired methicillin-resistant Staphylococcus aureus clonotypes
      ST228 and ST247 in Western Switzerland archived since 1998.
AB  - The development and maintenance of an arsenal of antibiotics is a major health
      care challenge. Ceftaroline is a new cephalosporin with activity against
      methicillin-resistant Staphylococcus aureus (MRSA); however, no reports
      concerning MRSA ceftaroline susceptibility have been reported in Switzerland. We
      tested the in vitro activity of ceftaroline against an archived set of 60 MRSA
      strains from the University Hospital of Geneva collected from 1994 to 2003. Our
      results surprisingly revealed ceftaroline-resistant strains (MIC, >1 MUg/ml in
      40/60 strains; EUCAST breakpoints, susceptible [S], <=1 MUg/ml; resistant [R], >1
      MUg/ml) were present from 1998 to 2003. The detected resistant strains
      predominantly belonged to sequence type 228 (ST228) (South German clonotype) but
      also to ST247 (Iberian clonotype). A sequence analysis of these strains revealed
      missense mutations in the penicillin-binding protein 2A (PBP2A) allosteric domain
      (N146K or E239K and N146K-E150K-G246E). The majority of our ST228 PBP2A mutations
      (N146K or E150K) were distinct from ST228 PBP2A allosteric domain mutations
      (primarily E239K) recently described for MRSA strains collected in Thailand and
      Spain during the 2010 Assessing Worldwide Antimicrobial Resistance Evaluation
      (AWARE) global surveillance program. We also found that similar allosteric domain
      PBP2A mutations (N146K) correlated with ceftaroline resistance in an independent
      external ST228 MRSA set obtained from the nearby University Hospital of Lausanne,
      Lausanne, Switzerland, collected from 2003 to 2008. Thus, ceftaroline resistance
      was observed in our archived strains (including two examples of an MIC of 4 ug/ml
      for the Iberian ST247 clonotype with the triple mutation N146K/E150K/G246E), at
      least as far back as 1998, considerably predating the commercial introduction of
      ceftaroline. Our results reinforce the notion that unknown parameters can
      potentially exert selective pressure on PBP2A that can subsequently modulate
      ceftaroline resistance. 

PMID- 25583723
TI  - SQ109, a new drug lead for Chagas disease.
AB  - We tested the antituberculosis drug SQ109, which is currently in advanced
      clinical trials for the treatment of drug-susceptible and drug-resistant
      tuberculosis, for its in vitro activity against the trypanosomatid parasite
      Trypanosoma cruzi, the causative agent of Chagas disease. SQ109 was found to be a
      potent inhibitor of the trypomastigote form of the parasite, with a 50%
      inhibitory concentration (IC50) for cell killing of 50 +/- 8 nM, but it had
      little effect (50% effective concentration [EC50], ~80 MUM) in a red blood cell
      hemolysis assay. It also inhibited extracellular epimastigotes (IC50, 4.6 +/- 1
      MUM) and the clinically relevant intracellular amastigotes (IC50, ~0.5 to 1 MUM),
      with a selectivity index of ~10 to 20. SQ109 caused major ultrastructural changes
      in all three life cycle forms, as observed by light microscopy, scanning electron
      microscopy (SEM), and transmission electron microscopy (TEM). It rapidly
      collapsed the inner mitochondrial membrane potential (Deltapsim) in succinate
      energized mitochondria, acting in the same manner as the uncoupler FCCP [carbonyl
      cyanide 4-(trifluoromethoxy)phenylhydrazone], and it caused the alkalinization of
      internal acidic compartments, effects that are likely to make major contributions
      to its mechanism of action. The compound also had activity against squalene
      synthase, binding to its active site; it inhibited sterol side-chain reduction
      and, in the amastigote assay, acted synergistically with the antifungal drug
      posaconazole, with a fractional inhibitory concentration index (FICI) of 0.48,
      but these effects are unlikely to account for the rapid effects seen on cell
      morphology and cell killing. SQ109 thus most likely acts, at least in part, by
      collapsing Deltapsi/DeltapH, one of the major mechanisms demonstrated previously
      for its action against Mycobacterium tuberculosis. Overall, the results suggest
      that SQ109, which is currently in advanced clinical trials for the treatment of
      drug-susceptible and drug-resistant tuberculosis, may also have potential as a
      drug lead against Chagas disease. 

PMID- 25583725
TI  - Moraxella catarrhalis AcrAB-OprM efflux pump contributes to antimicrobial
      resistance and is enhanced during cold shock response.
AB  - Moraxella catarrhalis is a common pathogen of the human respiratory tract.
      Multidrug efflux pumps play a major role in antibiotic resistance and virulence
      in many Gram-negative organisms. In the present study, the role of the AcrAB-OprM
      efflux pump in antibiotic resistance was investigated by constructing mutants
      that lack the acrA, acrB, and oprM genes in M. catarrhalis strain O35E. We
      observed a moderate (1.5-fold) decrease in the MICs of amoxicillin and cefotaxime
      and a marked (4.7-fold) decrease in the MICs of clarithromycin for acrA, acrB,
      and oprM mutants in comparison with the wild-type O35E strain. Exposure of the M.
      catarrhalis strains O35E and 300 to amoxicillin triggered an increased
      transcription of all AcrAB-OprM pump genes, and exposure of strains O35E, 300,
      and 415 to clarithromycin enhanced the expression of acrA and oprM mRNA.
      Inactivation of the AcrAB-OprM efflux pump genes demonstrated a decreased ability
      to invade epithelial cells compared to the parental strain, suggesting that acrA,
      acrB, and oprM are required for efficient invasion of human pharyngeal epithelial
      cells. Cold shock increases the expression of AcrAB-OprM efflux pump genes in all
      three M. catarrhalis strains tested. Increased expression of AcrAB-OprM pump
      genes after cold shock leads to a lower accumulation of Hoechst 33342 (H33342), a
      substrate of AcrAB-OprM efflux pumps, indicating that cold shock results in
      increased efflux activity. In conclusion, the AcrAB-OprM efflux pump appears to
      play a role in the antibiotic resistance and virulence of M. catarrhalis and is
      involved in the cold shock response. 

PMID- 25583726
TI  - Activities of N,N'-Diarylurea MMV665852 analogs against Schistosoma mansoni.
AB  - There is an unmet need to discover and develop novel antischistosomal drugs. As
      exemplified by MMV665852, N,N'-diarylureas have recently emerged as a promising
      antischistosomal chemotype. In this study, we evaluated the structure-activity
      relationships of 46 commercially available analogs of MMV665852 on newly
      transformed schistosomula (NTS) and adult Schistosoma mansoni worms in vitro.
      Active compounds were evaluated with a cytotoxicity assay, in silico
      calculations, metabolic stability studies, and an in vivo assay with mice
      harboring adult S. mansoni worms. Of the 46 compounds tested at 33.3 MUM, 13 and
      14 compounds killed NTS and adult worms, respectively, within 72 h. Nine
      compounds had 90% inhibitory concentrations (IC90s) of <=10 MUM against adult
      worms, with selectivity indexes of >=2.8. Their physicochemical properties and
      permeation through an artificial membrane indicated good to moderate intestinal
      absorption. Their metabolic stabilities ranged from low to high. Despite
      satisfactory in vitro results and in silico predictions, only one compound
      resulted in a statistically significant worm burden reduction (66%) after
      administration of a single oral dose of 400 mg/kg of body weight to S. mansoni
      infected mice. Worm burden reductions of 0 to 43% were observed for the remaining
      eight compounds tested. In conclusion, several analogs of the N,N'-diarylurea
      MMV665852 had high efficacy against S. mansoni in vitro and favorable
      physicochemical properties for permeation through the intestinal wall. To
      counteract the low efficacy observed in the mouse model, further investigations
      should focus on identifying compounds with improved solubility and
      pharmacokinetic properties. 

PMID- 25583727
TI  - Lung concentrations of ceftazidime administered by continuous versus intermittent
      infusion in patients with ventilator-associated pneumonia.
AB  - Ceftazidime is a beta-lactam compound that exerts a time-dependent bactericidal
      effect. Numerous arguments are in favor of continuous administration of
      ceftazidime, both for reasons of clinical efficacy and to preserve
      bacteriological mutation. We report a prospective, single-center, parallel-group,
      randomized, controlled trial comparing two modes of administration of
      ceftazidime, namely, continuous administration (loading dose of 20 mg/kg of body
      weight followed by 60 mg/kg/day) versus intermittent administration (20 mg/kg
      over 30 min every 8 h) in 34 patients with ventilator-associated pneumonia due to
      Gram-negative bacilli. The study was performed over 48 h with 13 and 18
      assessments of serum ceftazidime in the continuous-infusion group (group A) and
      the intermittent-fusion group (group B), respectively. Bronchoalveolar lavage
      (BAL) was performed at steady state in both groups at 44 h to determine
      ceftazidime levels in the epithelial lining fluid. We chose a predefined
      threshold of 20 mg/liter for serum concentrations of ceftazidime because of
      ecological conditions in our center. The median time above 20 mg/liter (T>20 mg)
      was 100% in group A versus 46% in group B. In group A, 14/17 patients had 100%
      T>20 mg, versus only 1/17 patients in group B. In the epithelial lining fluid,
      the median concentration of ceftazidime was 12 mg/liter in group A versus 6
      mg/liter in group B. A threshold of 8 mg/liter in the epithelial lining fluid was
      achieved twice as often in group A as in group B. This study of ceftazidime
      concentrations in the epithelial lining fluid indicates that continuous infusion
      presents advantages in terms of pharmacodynamics and predictable efficacy in
      patients presenting ventilator-associated pneumonia. 

PMID- 25583728
TI  - Epoxy-alpha-lapachone has in vitro and in vivo anti-leishmania (Leishmania)
      amazonensis effects and inhibits serine proteinase activity in this parasite.
AB  - Leishmania (Leishmania) amazonensis is a protozoan that causes infections with a
      broad spectrum of clinical manifestations. The currently available
      chemotherapeutic treatments present many problems, such as several adverse side
      effects and the development of resistant strains. Natural compounds have been
      investigated as potential antileishmanial agents, and the effects of epoxy-alpha
      lapachone on L. (L.) amazonensis were analyzed in the present study. This
      compound was able to cause measurable effects on promastigote and amastigote
      forms of the parasite, affecting plasma membrane organization and leading to
      death after 3 h of exposure. This compound also had an effect in experimentally
      infected BALB/c mice, causing reductions in paw lesions 6 weeks after treatment
      with 0.44 mM epoxy-alpha-lapachone (mean lesion area, 24.9 +/- 2.0 mm(2)),
      compared to untreated animals (mean lesion area, 30.8 +/- 2.6 mm(2)) or animals
      treated with Glucantime (mean lesion area, 28.3 +/- 1.5 mm(2)). In addition, the
      effects of this compound on the serine proteinase activities of the parasite were
      evaluated. Serine proteinase-enriched fractions were extracted from both
      promastigotes and amastigotes and were shown to act on specific serine proteinase
      substrates and to be sensitive to classic serine proteinase inhibitors
      (phenylmethylsulfonyl fluoride, aprotinin, and antipain). These fractions were
      also affected by epoxy-alpha-lapachone. Furthermore, in silico simulations
      indicated that epoxy-alpha-lapachone can bind to oligopeptidase B (OPB) of L.
      (L.) amazonensis, a serine proteinase, in a manner similar to that of antipain,
      interacting with an S1 binding site. This evidence suggests that OPB may be a
      potential target for epoxy-alpha-lapachone and, as such, may be related to the
      compound's effects on the parasite. 

PMID- 25583729
TI  - Inhibition of protein synthesis and malaria parasite development by drug
      targeting of methionyl-tRNA synthetases.
AB  - Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes that couple cognate
      tRNAs with amino acids to transmit genomic information for protein translation.
      The Plasmodium falciparum nuclear genome encodes two P. falciparum methionyl-tRNA
      synthetases (PfMRS), termed PfMRS(cyt) and PfMRS(api). Phylogenetic analyses
      revealed that the two proteins are of primitive origin and are related to
      heterokonts (PfMRS(cyt)) or proteobacteria/primitive bacteria (PfMRS(api)). We
      show that PfMRS(cyt) localizes in parasite cytoplasm, while PfMRS(api) localizes
      to apicoplasts in asexual stages of malaria parasites. Two known bacterial MRS
      inhibitors, REP3123 and REP8839, hampered Plasmodium growth very effectively in
      the early and late stages of parasite development. Small-molecule drug-like
      libraries were screened against modeled PfMRS structures, and several "hit"
      compounds showed significant effects on parasite growth. We then tested the
      effects of the hit compounds on protein translation by labeling nascent proteins
      with (35)S-labeled cysteine and methionine. Three of the tested compounds reduced
      protein synthesis and also blocked parasite growth progression from the ring
      stage to the trophozoite stage. Drug docking studies suggested distinct modes of
      binding for the three compounds, compared with the enzyme product methionyl
      adenylate. Therefore, this study provides new targets (PfMRSs) and hit compounds
      that can be explored for development as antimalarial drugs. 

PMID- 25583730
TI  - Mycobacterium tuberculosis gyrase inhibitors as a new class of antitubercular
      drugs.
AB  - One way to speed up the TB drug discovery process is to search for antitubercular
      activity among compound series that already possess some of the key properties
      needed in anti-infective drug discovery, such as whole-cell activity and oral
      absorption. Here, we present MGIs, a new series of Mycobacterium tuberculosis
      gyrase inhibitors, which stem from the long-term efforts GSK has dedicated to the
      discovery and development of novel bacterial topoisomerase inhibitors (NBTIs).
      The compounds identified were found to be devoid of fluoroquinolone (FQ) cross
      resistance and seem to operate through a mechanism similar to that of the
      previously described NBTI GSK antibacterial drug candidate. The remarkable in
      vitro and in vivo antitubercular profiles showed by the hits has prompted us to
      further advance the MGI project to full lead optimization. 

PMID- 25583731
TI  - Characterization of a novel small molecule that potentiates beta-lactam activity
      against gram-positive and gram-negative pathogens.
AB  - In a loss-of-viability screen using small molecules against methicillin-resistant
      Staphylococcus aureus (MRSA) strain USA300 with a sub-MIC of a beta-lactam, we
      found a small molecule, designated DNAC-1, which potentiated the effect of
      oxacillin (i.e., the MIC of oxacillin decreased from 64 to 0.25 MUg/ml).
      Fluorescence microscopy indicated a disruption in the membrane structures within
      15 min of exposure to DNAC-1 at 2* MIC. This permeabilization was accompanied by
      a rapid loss of membrane potential, as monitored by use of the DiOC2 (3,3'
      diethyloxacarbocyanine iodide) dye. Macromolecular analysis showed the inhibition
      of staphylococcal cell wall synthesis by DNAC-1. Transmission electron microscopy
      of treated MRSA USA300 cells revealed a slightly thicker cell wall, together with
      mesosome-like projections into the cytosol. The exposure of USA300 cells to DNAC
      1 was associated with the mislocalization of FtsZ accompanied by the localization
      of penicillin-binding protein 2 (PBP2) and PBP4 away from the septum, as well as
      mild activation of the vraRS-mediated cell wall stress response. However, DNAC-1
      does not have any generalized toxicity toward mammalian host cells. DNAC-1 in
      combination with ceftriaxone is also effective against an assortment of Gram
      negative pathogens. Using a murine subcutaneous coinjection model with 10(8) CFU
      of USA300 as a challenge inoculum, DNAC-1 alone or DNAC-1 with a sub-MIC of
      oxacillin resulted in a 6-log reduction in bacterial load and decreased abscess
      formation compared to the untreated control. We propose that DNAC-1, by exerting
      a bimodal effect on the cell membrane and cell wall, is a viable candidate in the
      development of combination therapy against many common bacterial pathogens. 

PMID- 25583733
TI  - Clinical trials: outcome measures.

PMID- 25583732
TI  - In vitro antibacterial activity of the ceftazidime-avibactam combination against
      enterobacteriaceae, including strains with well-characterized beta-lactamases.
AB  - The novel beta-lactamase inhibitor avibactam is a potent inhibitor of class A,
      class C, and some class D enzymes. The in vitro antibacterial activity of the
      ceftazidime-avibactam combination was determined for a collection of
      Enterobacteriaceae clinical isolates; this collection was enriched for resistant
      strains, including strains with characterized serine beta-lactamases. The
      inhibitor was added either at fixed weight ratios to ceftazidime or at fixed
      concentrations, with the latter type of combination consistently resulting in
      greater potentiation of antibacterial activity. In the presence of 4 MUg/ml of
      avibactam, the ceftazidime MIC50 and MIC90 (0.25 and 2 MUg/ml, respectively) were
      both below the CLSI breakpoint for ceftazidime. Further comparisons with
      reference antimicrobial agents were performed using this fixed inhibitor
      concentration. Against most ceftazidime-susceptible and -nonsusceptible isolates,
      the addition of avibactam resulted in a significant increase in ceftazidime
      activity, with MICs generally reduced 256-fold for extended-spectrum beta
      lactamase (ESBL) producers, 8- to 32-fold for CTX-M producers, and >128-fold for
      KPC producers. Overall, MICs of a ceftazidime-avibactam combination were
      significantly lower than those of the comparators piperacillin-tazobactam,
      cefotaxime, ceftriaxone, and cefepime and similar or superior to those of
      imipenem. 

PMID- 25583735
TI  - Privately run trust is first in England to be rated "inadequate" on patient care.

PMID- 25583734
TI  - DAMP, an acidotropic pH indicator, can be used as a tool to visualize non
      esterified cholesterol in cells.
AB  - Cholesterol-rich regions are attractive targets for studying metabolic disorders
      that involve accumulation of cholesterol. Despite efforts to develop probes for
      labelling cholesterol-rich regions in cells, few of these reagents have a low
      molecular weight. Previous studies have shown that the acidotropic pH indicator,
      N-{3-[(2,4-dinitrophenyl)amino]propyl}-N-(3-aminopropyl)methylamine
      dihydrochloride (DAMP), reacts with cholesterol-rich organelles, such as
      endocrine secretary granules from endocrine cells. In this study, we demonstrated
      that DAMP could react with free cholesterol in a dose-dependent manner, and DAMP
      was able to detect cholesterol-rich subcellular organelles. DAMP was sufficiently
      potent to detect free cholesterol-enriched organs, but was unable to detect
      atherosclerotic plaques primarily composed of esterified cholesterol. Taken
      together, these results demonstrate that DAMP facilitates the study of
      cholesterol-enriched lipid rafts and disorders which involve cholesterol
      accumulation. 

PMID- 25583736
TI  - Six-year clinical study of firework-related eye injuries in North China.
AB  - PURPOSE: To analyse the demographic data, clinical characteristics, management
      and prognosis of patients with firework-related eye injuries. METHODS: A
      retrospective review was performed of patients with eye injuries related to
      fireworks referred to TianJin Eye Hospital in North China from 2008 to 2013.
      Demographic information, clinical features, management and visual outcome were
      analysed and prognosis factors were evaluated. RESULTS: Ninety-nine patients (86
      men) with 118 eye injuries were enrolled in the study. The average age of the
      patients was 32.0+/-20.5 years; 70/99 (70.7%) were aged >20 years. Eighty-one of
      the patients had been lighting the fireworks while the rest were bystanders. The
      main ophthalmic manifestations were hyphaema, vitreous haemorrhage,
      corneal/sclera/corneoscleral open globe injury, eyelid laceration, traumatic
      cataract, retinal/choroid detachment, endophthalmitis and intraocular foreign
      body (IOFB). Ninety patients required surgical intervention including repair of
      open globe injury, vitrectomy, cataract extraction and enucleation. 56/118 eyes
      (47.5%) received multiple operations. After treatment, final best-corrected
      visual acuity (BCVA) significantly improved (p=0.015). Some factors were
      significantly correlated with better final BCVA, including initial BCVA
      (p=0.036), closed globe injury (p=0.031), absence of endophthalmitis (p=0.014),
      absence of IOFB (p=0.024) and absence of retinal detachment (p=0.046).
      CONCLUSIONS: Firework-related eye injuries mainly occur in adult men and result
      in severe visual damage. The most common clinical manifestations are hyphaema and
      vitreous haemorrhage. Better initial BCVA and closed globe injury have a better
      visual result while endophthalmitis, IOFB and retinal detachment have a negative
      visual outcome. Improved eye protection, along with enhanced public education and
      legal ban on fireworks, could reduce the incidence of eye injuries.

PMID- 25583738
TI  - Republished: mucinous tumours of appendix and ovary: an overview and evaluation
      of current practice.
AB  - Mucinous lesions of the appendix and ovary are commonly encountered in routine
      practice. There are several published classification schemes for appendiceal
      mucinous neoplasms with resultant inconsistent use of terms and clinical doubt.
      While nomenclature is more settled with regards to ovarian mucinous neoplasms,
      the difficulty here lies with distinguishing primary from secondary mucinous
      tumours. This review highlights the terminology and nomenclature for appendiceal
      mucinous tumours, the relationship with ovarian mucinous neoplasms and
      pseudomyxoma peritonei, and the features that assist in separating primary from
      secondary ovarian mucinous tumours. 

PMID- 25583737
TI  - Documentation and treatment of hypertension: quality of care and missed
      opportunities in a family medicine resident clinic.
AB  - BACKGROUND: In the USA, uncontrolled hypertension contributes to 1000 deaths a
      day. However, little is known about the quality of hypertension management in
      family medicine resident clinics. OBJECTIVES: To examine rates of documentation
      and treatment of elevated blood pressure, and to identify missed opportunities to
      address hypertension. Study design A cross-sectional chart review of 1011 adult
      patient visits between 2 January and 4 February 2013 was performed in a resident
      run federally qualified health centre. For patients with elevated blood pressure
      at time of visit, we noted whether or not the residents had documented a
      diagnosis or discussion of hypertension and the presence or absence of a
      treatment plan. We compared these rates with those from a national sample of
      primary care physicians. RESULTS: 262/1011 (26%) of adult patients had elevated
      blood pressure at time of visit. Of those, 115/262 (44%) had documentation and a
      plan for treatment, 79/262 (30%) had documentation but no plan, and 68/262 (26%)
      had neither documentation nor plan. Nationally, 45% of patients are diagnosed and
      treated compared with 44% of study visits with documentation and treatment.
      CONCLUSIONS: Fewer than half of visits of patients with elevated blood pressure
      resulted in both documentation and a treatment plan. Nevertheless, these rates
      are comparable to national providers. Elevated blood pressure was more likely to
      be missed during acute visits and in patients with less elevated blood pressure.

PMID- 25583740
TI  - Cerebral microhaemorrhages secondary to fat embolus syndrome in sickle cell
      disease.

PMID- 25583741
TI  - Dannie Abse: doctor and poet.

PMID- 25583739
TI  - Republished: symptomatic reflux disease: the present, the past and the future.
AB  - The worldwide incidence of GORD and its complications is increasing along with
      the exponentially increasing problem of obesity. Of particular concern is the
      relationship between central adiposity and GORD complications, including
      oesophageal adenocarcinoma. Driven by progressive insight into the epidemiology
      and pathophysiology of GORD, the earlier belief that increased gastroesophageal
      reflux mainly results from one dominant mechanism has been replaced by acceptance
      that GORD is multifactorial. Instigating factors, such as obesity, age, genetics,
      pregnancy and trauma may all contribute to mechanical impairment of the
      oesophagogastric junction resulting in pathological reflux and accompanying
      syndromes. Progression of the disease by exacerbating and perpetuating factors
      such as obesity, neuromuscular dysfunction and oesophageal fibrosis ultimately
      lead to development of an overt hiatal hernia. The latter is now accepted as a
      central player, impacting on most mechanisms underlying gastroesophageal reflux
      (low sphincter pressure, transient lower oesophageal sphincter relaxation,
      oesophageal clearance and acid pocket position), explaining its association with
      more severe disease and mucosal damage. Since the introduction of proton pump
      inhibitors (PPI), clinical management of GORD has markedly changed, shifting the
      therapeutic challenge from mucosal healing to reduction of PPI-resistant
      symptoms. In parallel, it became clear that reflux symptoms may result from
      weakly acidic or non-acid reflux, insight that has triggered the search for new
      compounds or minimally invasive procedures to reduce all types of reflux. In
      summary, our view on GORD has evolved enormously compared to that of the past,
      and without doubt will impact on how to deal with GORD in the future. 

PMID- 25583742
TI  - Creative subversion.

PMID- 25583743
TI  - The effect of beverage type on alcoholic psychoses rate in Russia.
AB  - AIMS: To test the hypothesis of beverage-specific effect in Russia on the
      incidence rate of alcoholic psychoses (a known indicator of a population's
      alcohol-related problems). METHODS: Time series analytical modeling techniques
      (ARIMA) were used to examine the relation between the sales of different
      alcoholic beverages (vodka, wine, beer) and alcoholic psychoses incidence rate
      between 1970 and 2013. RESULTS: The analysis suggests that of the three beverages
      vodka alone was associated with alcoholic psychoses incidence rate. The estimated
      effect of vodka sales on the alcohol psychoses rate is statistically significant:
      a 1 l per person per year increase in vodka sales would result in a 23.4%
      increase in the alcoholic psychoses incidence rate. CONCLUSION: The incidence of
      alcoholic psychoses is more responsive to changes in vodka sales per capita than
      wine or beer sales.

PMID- 25583744
TI  - Regulator of devices investigates complaints about multifocal lens.

PMID- 25583745
TI  - Comment on: Efficacy and safety of daptomycin for the treatment of infectious
      disease: a meta-analysis based on randomized controlled trials.

PMID- 25583746
TI  - Efficacy and safety of chloramphenicol: joining the revival of old antibiotics?
      Systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVES: Chloramphenicol is an old broad-spectrum antibiotic. We assessed its
      efficacy and safety. METHODS: This was a systematic review and meta-analysis.
      Electronic databases were searched to identify randomized controlled trials
      (RCTs) that assessed patients, of any age, with systemic bacterial infections
      that can cause sepsis and compared chloramphenicol alone versus other
      antibiotics. No restrictions on the date of publication, language or publication
      status were applied. The primary outcome assessed was overall mortality. RESULTS:
      Sixty-six RCTs fulfilled the inclusion criteria, and these included 9711
      patients. We found a higher mortality with chloramphenicol for respiratory tract
      infections [risk ratio (RR) 1.40, 95% CI 1.00-1.97] and meningitis (RR 1.27, 95%
      CI 1.00-1.60), both without heterogeneity. The point estimate was similar for
      enteric fever, without statistical significance. No statistically significant
      difference was found between chloramphenicol and other antibiotics regarding
      treatment failure, except for enteric fever (RR 1.46, 95% CI 1.07-2.00, without
      heterogeneity). This difference derived mainly from studies comparing
      chloramphenicol with fluoroquinolones (RR 1.85, 95% CI 1.07-3.2). There were no
      statistically significant differences between chloramphenicol and other
      antibiotics in terms of adverse events, including haematological events, except
      for anaemia, which occurred more frequently with chloramphenicol (RR 2.80, 95% CI
      1.65-4.75, I(2) =0%), and gastrointestinal side effects, which were less frequent
      with chloramphenicol (RR 0.67, 95% CI 0.46-0.99, I(2) =0%). Many of the studies
      included were sponsored by pharmaceutical companies marketing the comparator drug
      to chloramphenicol, and this might have influenced the results. CONCLUSIONS:
      Chloramphenicol cannot be recommended as a first-line treatment for respiratory
      tract infections, meningitis or enteric fever as alternatives are probably more
      effective. Chloramphenicol is as safe as treatment alternatives for short
      antibiotic courses. RCTs are needed to test this treatment against MDR organisms
      when better alternatives do not exist.

PMID- 25583747
TI  - Efficacy and safety of daptomycin for the treatment of infectious disease: a meta
      analysis based on randomized controlled trials-authors' response.

PMID- 25583748
TI  - Heterogeneous hydrolytic features for OXA-48-like beta-lactamases.
AB  - OBJECTIVES: Carbapenem-hydrolysing class D beta-lactamases of the OXA-48 type are
      increasingly reported from Enterobacteriaceae. beta-Lactamase OXA-48 hydrolyses
      penicillins very efficiently, but carbapenems only weakly and spares broad
      spectrum cephalosporins. Recently, diverse OXA-48-like beta-lactamases have been
      identified worldwide (OXA-162, OXA-181, OXA-163, OXA-204 and OXA-232). They
      differ by few amino acid substitutions or by amino acid deletions. METHODS:
      blaOXA-48, blaOXA-162, blaOXA-163, blaOXA-181, blaOXA-204 and blaOXA-232 were
      cloned into the same expression vector and expressed in the same Escherichia coli
      background. Kinetic studies were performed with enzymes purified by ion-exchange
      chromatography. Determination of hydrolytic activities was performed by UV
      spectrophotometry. MICs were determined for all recombinant strains, using as
      background either the WT E. coli TOP10 strain or a porin-deficient E. coli
      strain. RESULTS: Kinetic studies showed that OXA-162 and OXA-204 shared the same
      hydrolytic properties as OXA-48. On the other hand, OXA-181 possessed a higher
      ability to hydrolyse carbapenems, while OXA-232 hydrolysed those substrates less
      efficiently. In contrast to the other OXA-48-like beta-lactamases, OXA-163
      hydrolysed broad-spectrum cephalosporins very efficiently, but did not possess
      significant carbapenemase activity. Although several of these OXA-48-like enzymes
      possess low activity against carbapenems, MICs of carbapenems were significantly
      elevated when determined for strains possessing permeability defects.
      CONCLUSIONS: A detailed comparative analysis of the kinetic properties of the OXA
      48-like beta-lactamases is provided here. It clarifies the respective features of
      each OXA-48-like variant and their respective impacts in terms of carbapenem
      resistance.

PMID- 25583750
TI  - Analysis of a long-term outbreak of XDR Pseudomonas aeruginosa: a molecular
      epidemiological study.
AB  - OBJECTIVES: Here we report on a long-term outbreak from 2009 to 2012 with an XDR
      Pseudomonas aeruginosa on two wards at a university hospital in southern Germany.
      METHODS: Whole-genome sequencing was performed on the outbreak isolates and a
      core genome was constructed for molecular epidemiological analysis. We applied a
      time-place-sequence algorithm to improve estimation of transmission
      probabilities. RESULTS: By using conventional infection control methods we
      identified 49 P. aeruginosa strains, including eight environmental isolates that
      belonged to ST308 (by MLST) and carried the metallo-beta-lactamase IMP-8.
      Phylogenetic analysis on the basis of a non-recombinant core genome that
      contained 22 outbreak-specific SNPs revealed a pattern of four dominant clades
      with a strong phylogeographic structure and allowed us to determine the potential
      temporal origin of the outbreak to July 2008, 1 year before the index case was
      diagnosed. Superspreaders at the root of clades exhibited a high number of
      probable and predicted transmissions, indicating their exceptional position in
      the outbreak. CONCLUSIONS: Our results suggest that the initial expansion of
      dominant sublineages was driven by a few superspreaders, while environmental
      contamination seemed to sustain the outbreak for a long period despite regular
      environmental control measures.

PMID- 25583749
TI  - Tenofovir plasma concentrations related to estimated glomerular filtration rate
      changes in first-line regimens in African HIV-infected patients: ANRS 12115
      DAYANA substudy.
AB  - OBJECTIVES: An open-label randomized trial (DAYANA) was conducted in sub-Saharan
      settings to evaluate four different regimens containing tenofovir disoproxil
      fumarate as first-line treatment for HIV infection. The objectives of the present
      substudy were to assess the relationship between trough concentrations of
      tenofovir in plasma collected after 24 h (C24) and estimated glomerular
      filtration rates (eGFR) calculated by the different formulae that are available.
      METHODS: The criteria for eligibility were those of the DAYANA trial, recruiting
      naive patients. The four tenofovir regimens were: Group 1,
      tenofovir/emtricitabine/nevirapine; Group 2, tenofovir/lopinavir/ritonavir; Group
      3, tenofovir/emtricitabine/zidovudine; and Group 4,
      tenofovir/emtricitabine/efavirenz. The C24 of tenofovir was determined using LC
      MS/MS. The eGFR was calculated using the Cockcroft-Gault, Modification of Diet in
      Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD
      EPI) formulae. RESULTS: The median C24 of tenofovir was 42 ng/mL. The C24 of
      tenofovir was higher with lopinavir/ritonavir than with the other three regimens:
      at Week 4, 84 ng/mL versus 25 ng/mL; and at Week 48, 81 ng/mL versus 52 ng/mL.
      The baseline merged eGFR was 98.2 mL/min/1.73 m(2) with the CKD-EPI equation.
      Only the mean changes in eGFR in Group 2 differed from the absolute value of zero
      (-8.2 mL/min/1.73 m(2)) with the CKD-EPI equation between baseline and Week 48.
      The Cockcroft-Gault formula is inappropriate for these African patients because
      it underestimated the baseline eGFR and overestimated the changes in eGFR between
      baseline and Week 48. CONCLUSIONS: In this population of mostly female HIV-1
      infected African patients, tenofovir plasma overexposure was associated with
      PI/ritonavir and a time-dependent decrease in eGFR, probably via an inhibition of
      MRP2/MRP4 efflux transporters. The close monitoring over time of the eGFR using
      MDRD or CKD-EPI calculations and by using other biomarkers of renal disorder
      should be proposed as an alternative to therapeutic drug monitoring in resource
      limited countries.

PMID- 25583751
TI  - SLC29A1 polymorphism and prediction of anaemia severity in patients with chronic
      hepatitis C receiving triple therapy with telaprevir.
AB  - OBJECTIVES: The equilibrative nucleoside transporter 1 (ENT1) is the main protein
      involved in ribavirin cellular uptake. Polymorphisms at the SLC29A1 gene,
      encoding ENT1, may influence ribavirin-associated anaemia, which is observed at a
      higher incidence with telaprevir in combination with pegylated-IFNalpha and
      ribavirin than with pegylated-IFNalpha and ribavirin alone. In this study, we
      investigated the role of the rs760370 SLC29A1 variant in ribavirin-induced
      anaemia in chronic hepatitis C patients treated with telaprevir-based triple
      therapy. METHODS: Forty patients infected with hepatitis C virus (HCV) genotype 1
      and starting anti-HCV therapy with telaprevir in combination with pegylated
      IFN/ribavirin were prospectively evaluated for SNPs at the SLC29A1 gene and
      inosine triphosphatase (ITPA) genes using a real-time PCR system. RESULTS: 40% of
      patients developed severe anaemia with a haemoglobin (Hb) decline >= 5 g/dL from
      the pretreatment value. The SLC29A1 rs760370 GG genotype was associated with the
      severity of Hb decrease as expressed by the median (IQR) Hb nadir change from
      baseline [-5.4 (-5.6; -5.0) g/dL in GG versus -4.2 (-5.1; -3.4) in AA/AG
      genotype; P=0.05] and by the Hb decrease >= 5 g/dL by week 12 (77.8% of GG
      carriers versus 24% of AA/AG; P<0.01). In multivariate analysis, older age
      (P=0.03), lower baseline Hb concentration (P=0.02) and SLC29A1 rs760370 GG
      (P=0.02) were associated with the development of severe anaemia during treatment,
      whereas no association was found with ITPA SNPs in our population receiving
      telaprevir-based therapy. CONCLUSIONS: In patients with chronic hepatitis C
      receiving telaprevir-based therapy, SNP rs760370A>G at the SLC29A1 gene
      influences the severity of ribavirin-induced anaemia, possibly mirroring the
      erythrocyte uptake of ribavirin.

PMID- 25583752
TI  - Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart
      Study.
AB  - OBJECTIVE: Little is known about arsenic metabolism in diabetes development. We
      investigated the prospective associations of low-moderate arsenic exposure and
      arsenic metabolism with diabetes incidence in the Strong Heart Study. RESEARCH
      DESIGN AND METHODS: A total of 1,694 diabetes-free participants aged 45-75 years
      were recruited in 1989-1991 and followed through 1998-1999. We used the
      proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and
      dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the
      biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose >= 126
      mg/dL, 2-h glucose >= 200 mg/dL, self-reported diabetes history, or self-reported
      use of antidiabetic medications. RESULTS: Over 11,263.2 person-years of follow
      up, 396 participants developed diabetes. Using the leave-one-out approach to
      model the dynamics of arsenic metabolism, we found that lower MMA% was associated
      with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence
      for a 5% increase in MMA% were 0.77 (0.63-0.93) and 0.82 (0.73-0.92) when iAs%
      and DMA%, respectively, were left out of the model. DMA% was associated with
      higher diabetes incidence only when MMA% decreased (left out of the model) but
      not when iAs% decreased. iAs% was also associated with higher diabetes incidence
      when MMA% decreased. The association between MMA% and diabetes incidence was
      similar by age, sex, study site, obesity, and urine iAs concentrations.
      CONCLUSIONS: Arsenic metabolism, particularly lower MMA%, was prospectively
      associated with increased incidence of diabetes. Research is needed to evaluate
      whether arsenic metabolism is related to diabetes incidence per se or through its
      close connections with one-carbon metabolism.

PMID- 25583755
TI  - Russia bans transsexuals and people with personality disorders from driving.

PMID- 25583753
TI  - Preexisting insulin autoantibodies predict efficacy of otelixizumab in preserving
      residual beta-cell function in recent-onset type 1 diabetes.
AB  - OBJECTIVE: Immune intervention trials in recent-onset type 1 diabetes would
      benefit from biomarkers associated with good therapeutic response. In the
      previously reported randomized placebo-controlled anti-CD3 study (otelixizumab;
      GlaxoSmithKline), we tested the hypothesis that specific diabetes autoantibodies
      might serve this purpose. RESEARCH DESIGN AND METHODS: In the included patients
      (n = 40 otelixizumab, n = 40 placebo), beta-cell function was assessed as area
      under the curve (AUC) C-peptide release during a hyperglycemic glucose clamp at
      baseline (median duration of insulin treatment: 6 days) and every 6 months until
      18 months after randomization. (Auto)antibodies against insulin (I[A]A), GAD
      (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A) were determined on stored sera by liquid
      phase radiobinding assay. RESULTS: At baseline, only better preserved AUC C
      peptide release and higher levels of IAA were associated with better preservation
      of beta-cell function and lower insulin needs under anti-CD3 treatment. In
      multivariate analysis, IAA (P = 0.022) or the interaction of IAA and C-peptide (P
      = 0.013) independently predicted outcome together with treatment. During follow
      up, good responders to anti-CD3 treatment (i.e., IAA(+) participants with
      relatively preserved beta-cell function [>= 25% of healthy control subjects])
      experienced a less pronounced insulin-induced rise in I(A)A and lower insulin
      needs. GADA, IA-2A, and ZnT8A levels were not influenced by anti-CD3 treatment,
      and their changes showed no relation to functional outcome. CONCLUSIONS: There is
      important specificity of IAA among other diabetes autoantibodies to predict good
      therapeutic response of recent-onset type 1 diabetic patients to anti-CD3
      treatment. If confirmed, future immune intervention trials in type 1 diabetes
      should consider both relatively preserved functional beta-cell mass and presence
      of IAA as inclusion criteria.

PMID- 25583754
TI  - Combination of empagliflozin and linagliptin as second-line therapy in subjects
      with type 2 diabetes inadequately controlled on metformin.
AB  - OBJECTIVE: To evaluate the efficacy and safety of combinations of
      empagliflozin/linagliptin as second-line therapy in subjects with type 2 diabetes
      inadequately controlled on metformin. RESEARCH DESIGN AND METHODS: Subjects were
      randomized to a combination of empagliflozin 25 mg/linagliptin 5 mg (n = 137),
      empagliflozin 10 mg/linagliptin 5 mg (n = 136), empagliflozin 25 mg (n = 141),
      empagliflozin 10 mg (n = 140), or linagliptin 5 mg (n = 132) as add-on to
      metformin for 52 weeks. The primary end point was change from baseline in HbA1c
      at week 24. RESULTS: At week 24, reductions in HbA1c (mean baseline 7.90-8.02%
      [62.8-64.1 mmol/mol]) with empagliflozin/linagliptin were superior to those with
      empagliflozin or linagliptin alone as add-on to metformin; adjusted mean (SE)
      changes from baseline were -1.19% (0.06) (-13.1 mmol/mol [0.7]) with
      empagliflozin 25 mg/linagliptin 5 mg, -1.08% (0.06) (-11.8 mmol/mol [0.7]) with
      empagliflozin 10 mg/linagliptin 5 mg, -0.62% (0.06) (-6.8 mmol/mol [0.7]) with
      empagliflozin 25 mg, -0.66% (0.06) (-7.2 mmol/mol [0.7]) with empagliflozin 10
      mg, and -0.70% (0.06) (-7.6 mmol/mol [0.7]) with linagliptin 5 mg (P < 0.001 for
      all comparisons). In these groups, respectively, 61.8, 57.8, 32.6, 28.0, and
      36.1% of subjects with baseline HbA1c >=7% (>=53 mmol/mol) had HbA1c <7% (<53
      mmol/mol) at week 24. Efficacy was maintained at week 52. The proportion of
      subjects with adverse events (AEs) over 52 weeks was similar across treatment
      arms (68.6-73.0%), with no hypoglycemic AEs requiring assistance. CONCLUSIONS:
      Combinations of empagliflozin/linagliptin as second-line therapy for 52 weeks
      significantly reduced HbA1c compared with the individual components and were well
      tolerated.

PMID- 25583756
TI  - Novel radiographic feature classification of knee osteochondritis dissecans: a
      multicenter reliability study.
AB  - BACKGROUND: Osteochondritis dissecans (OCD) is a vexing condition for patients,
      parents, and physicians because of the frequent slow healing and nonhealing that
      leads to prolonged treatment. Several features on plain radiographs have been
      identified as predictors of healing, but the reliability of their measurement has
      not been established. PURPOSE: To determine the inter- and intrarater reliability
      of several radiographic features used in the diagnosis, treatment, and prognosis
      of OCD femoral condyle lesions. STUDY DESIGN: Cohort study (Diagnosis); Level of
      evidence, 3. METHODS: Pretreatment anteroposterior, lateral, and notch
      radiographs of 45 knees containing OCD lesions of the medial or lateral femoral
      condyle were reviewed in blinded fashion by 7 orthopaedic physician raters from
      different institutions over a secure web portal at 2 time points over a month
      apart. Classification variables included lesion location, growth plate maturity,
      parent bone radiodensity, progeny bone fragmentation, progeny bone displacement,
      progeny bone contour, lesion boundary, and radiodensity of the lesion center and
      rim. Condylar width and lesion size were measured on all views. Interrater
      reliability was assessed using free-marginal kappa and intraclass correlations.
      Intrarater reliability was assessed using the Cohen kappa, linear-weighted kappa,
      and intraclass correlations based on measurement type. RESULTS: Raters had
      excellent reliability for differentiating medial and lateral lesions and growth
      plate maturity and for measuring condylar width and lesion size. In the subset of
      knees with visible bone in the lesion, the fragmentation, displacement, boundary,
      central radiodensity, and contour (concave/nonconcave) of the lesion bone were
      classified with moderate to substantial reliability. The radiodensity of the
      lesion rim and surrounding epiphyseal bone were classified with poor to fair
      reliability. CONCLUSION: Many diagnostic features of femoral condyle OCD lesions
      can be reliably classified on plain radiographs, supporting their future testing
      in multifactorial classification systems and multicenter research to develop
      prognostic algorithms. Other radiographic features should be excluded, however,
      because of poor reliability.

PMID- 25583757
TI  - Sports participation 2 years after anterior cruciate ligament reconstruction in
      athletes who had not returned to sport at 1 year: a prospective follow-up of
      physical function and psychological factors in 122 athletes.
AB  - BACKGROUND: A return to their preinjury level of sport is frequently expected
      within 1 year after anterior cruciate ligament (ACL) reconstruction, yet up to
      two-thirds of athletes may not have achieved this milestone. The subsequent
      sports participation outcomes of athletes who have not returned to their
      preinjury level sport by 1 year after surgery have not previously been
      investigated. PURPOSE: To investigate return-to-sport rates at 2 years after
      surgery in athletes who had not returned to their preinjury level sport at 1 year
      after ACL reconstruction. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: A consecutive cohort of competitive- and recreational-level athletes was
      recruited prospectively before undergoing ACL reconstruction at a private
      orthopaedic clinic. Participants were followed up at 1 and 2 years after surgery
      with a sports activity questionnaire that collected information regarding
      returning to sport, sports participation, and psychological responses. An
      independent physical therapist evaluated physical function at 1 year using hop
      tests and the International Knee Documentation Committee knee examination form
      and subjective knee evaluation. RESULTS: A group of 122 competitive- and
      recreational-level athletes who had not returned to their preinjury level sport
      at 1 year after ACL reconstruction participated. Ninety-one percent of the
      athletes returned to some form of sport after surgery. At 2 years after surgery,
      66% were playing sport, with 41% playing their preinjury level of sport and 25%
      playing a lower level of sport. Having a previous ACL reconstruction to either
      knee, poorer hop-test symmetry and subjective knee function, and more negative
      psychological responses were associated with not playing the preinjury level
      sport at 2 years. CONCLUSION: Most athletes who were not playing sport at 1 year
      had returned to some form of sport within 2 years after ACL reconstruction, which
      may suggest that athletes can take longer than the clinically expected time of 1
      year to return to sport. However, only 2 of every 5 athletes were playing their
      preinjury level of sport at 2 years after surgery. When the results of the
      current study were combined with the results of athletes who had returned to
      sport at 1 year, the overall rate of return to the preinjury level sport at 2
      years was 60%. Demographics, physical function, and psychological factors were
      related to playing the preinjury level sport at 2 years after surgery, supporting
      the notion that returning to sport after surgery is multifactorial.

PMID- 25583758
TI  - Arthroscopic distal clavicle resection in symptomatic acromioclavicular joint
      arthritis combined with rotator cuff tear: a prospective randomized trial.
AB  - BACKGROUND: The treatment of symptomatic acromioclavicular joint (ACJ) injury in
      the rotator cuff (RC) tear has not been well clarified. PURPOSE: To compare the
      clinical results between patients who had distal clavicle resection (DCR) and
      those who did not during RC repair. STUDY DESIGN: Randomized controlled trial;
      Level of evidence, 1. METHODS: From August 2008 to December 2009, a total of 56
      consecutive patients (58 shoulders) were included. All patients had either a full
      thickness or high-grade (>50%) RC tear, ACJ tenderness, arthritic change visible
      on plain radiographs, and a positive ACJ lidocaine injection test the day before
      surgery. Patients were randomized into 2 groups: DCR and RC repair (DCR+RCR
      group) and RC repair only (isolated RCR). Evaluation was performed
      preoperatively, at 6 months postoperatively, and at a final follow-up a minimum
      of 24 months postoperatively using the American Shoulder and Elbow Surgeons
      (ASES) score, the Constant shoulder score, range of motion examination, and pain
      visual analog scale (VAS). RESULTS: After simple randomization, 26 shoulders were
      allocated in the DCR+RCR group, and 32 were placed in the isolated RCR group.
      Five shoulders in the DCR+RCR group and 6 in the isolated RCR group were excluded
      from analysis due to loss of follow-up. Therefore, the evaluation was performed
      for 21 shoulders in the DCR+RCR group and 26 shoulders in the isolated RCR group.
      The mean follow-up period was 44.2 months in the DCR+RCR group and 44.0 months in
      the isolated RCR group. There were no differences in age, sex, symptom duration,
      RC tear size, or preoperative ASES, Constant, and VAS scores between the 2 groups
      (P > .05). At final follow-up, the ASES, Constant, and VAS scores were
      significantly improved in both groups (P < .001). There were no differences in
      ASES, Constant, and VAS scores between the 2 groups at final follow-up (P > .05),
      and there was no difference in residual ACJ tenderness (7 in the DCR+RCR group
      and 5 in the isolated RCR group) between the 2 groups (P = .270). CONCLUSION:
      There was no difference in the clinical evaluations between the combined
      arthroscopic DCR and RCR group and the isolated RCR group at a minimum 24-month
      follow-up. Arthroscopic DCR should be carefully considered in patients who have
      symptomatic ACJ arthritis with RC tears.

PMID- 25583759
TI  - Combined anatomic factors predicting risk of anterior cruciate ligament injury
      for males and females.
AB  - BACKGROUND: Knee joint geometry has been associated with risk of suffering an
      anterior cruciate ligament (ACL) injury; however, few studies have utilized
      multivariate analysis to investigate how different aspects of knee joint geometry
      combine to influence ACL injury risk. HYPOTHESES: Combinations of knee geometry
      measurements are more highly associated with the risk of suffering a noncontact
      ACL injury than individual measurements, and the most predictive combinations of
      measurements are different for males and females. STUDY DESIGN: Case-control
      study; Level of evidence, 3. METHODS: A total of 88 first-time, noncontact, grade
      III ACL-injured subjects and 88 uninjured matched-control subjects were
      recruited, and magnetic resonance imaging data were acquired. The geometry of the
      tibial plateau subchondral bone, articular cartilage, and meniscus; geometry of
      the tibial spines; and size of the femoral intercondylar notch and ACL were
      measured. Multivariate conditional logistic regression was used to develop risk
      models for ACL injury in females and males separately. RESULTS: For females, the
      best fitting model included width of the femoral notch at its anterior outlet and
      the posterior-inferior-directed slope of the lateral compartment articular
      cartilage surface, where a millimeter decrease in notch width and a degree
      increase in slope were independently associated with a 50% and 32% increase in
      risk of ACL injury, respectively. For males, a model that included ACL volume and
      the lateral compartment posterior meniscus to subchondral bone wedge angle was
      most highly associated with risk of ACL injury, where a 0.1 cm3 decrease in ACL
      volume (approximately 8% of the mean value) and a degree decrease in meniscus
      wedge angle were independently associated with a 43% and 23% increase in risk,
      correspondingly. CONCLUSION: Combinations of knee joint geometry measurements
      provided more information about the risk of noncontact ACL injury than individual
      measures, and the aspects of geometry that best explained the relationship
      between knee geometry and the risk of injury were different between males and
      females. Consequently, a female with both a decreased femoral notch width and an
      increased posterior-inferior-directed lateral compartment tibial articular
      cartilage slope combined or a male with a decreased ACL volume and decreased
      lateral compartment posterior meniscus angle were most at risk for sustaining an
      ACL injury.

PMID- 25583760
TI  - The stark reality of rheumatic heart disease.

PMID- 25583762
TI  - Meet the New JNCCN!

PMID- 25583763
TI  - After local therapy for esophageal cancer, should we continue to survey patients
      and, if so, why and how?

PMID- 25583761
TI  - Long-term forecasting and comparison of mortality in the Evaluation of the Xience
      Everolimus Eluting Stent vs. Coronary Artery Bypass Surgery for Effectiveness of
      Left Main Revascularization (EXCEL) trial: prospective validation of the SYNTAX
      Score II.
AB  - AIMS: To prospectively validate the SYNTAX Score II and forecast the outcomes of
      the randomized Evaluation of the Xience Everolimus-Eluting Stent Versus Coronary
      Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL)
      Trial. METHODS AND RESULTS: Evaluation of the Xience Everolimus Eluting Stent vs.
      Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization
      is a prospective, randomized multicenter trial designed to establish the efficacy
      and safety of percutaneous coronary intervention (PCI) with the everolimus
      eluting stent compared with coronary artery bypass graft (CABG) surgery in
      subjects with unprotected left-main coronary artery (ULMCA) disease and low
      intermediate anatomical SYNTAX scores (<33). After completion of patient
      recruitment in EXCEL, the SYNTAX Score II was prospectively applied to predict 4
      year mortality in the CABG and PCI arms. The 95% prediction intervals (PIs) for
      mortality were computed using simulation with bootstrap resampling (10 000
      times). For the entire study cohort, the 4-year predicted mortalities were 8.5
      and 10.5% in the PCI and CABG arms, respectively [odds ratios (OR) 0.79; 95% PI
      0.43-1.50). In subjects with low (<=22) anatomical SYNTAX scores, the predicted
      OR was 0.69 (95% PI 0.34-1.45); in intermediate anatomical SYNTAX scores (23-32),
      the predicted OR was 0.93 (95% PI 0.53-1.62). Based on 4-year mortality
      predictions in EXCEL, clinical characteristics shifted long-term mortality
      predictions either in favour of PCI (older age, male gender and COPD) or CABG
      (younger age, lower creatinine clearance, female gender, reduced left ventricular
      ejection fraction). CONCLUSION: The SYNTAX Score II indicates at least an
      equipoise for long-term mortality between CABG and PCI in subjects with ULMCA
      disease up to an intermediate anatomical complexity. Both anatomical and clinical
      characteristics had a clear impact on long-term mortality predictions and
      decision making between CABG and PCI.

PMID- 25583764
TI  - The birth of NCCN.

PMID- 25583765
TI  - Cotreatment of hairy cell leukemia and melanoma with the BRAF inhibitor
      dabrafenib.
AB  - The activating BRAF mutation p.V600E has been identified in many cancers,
      including colon and lung adenocarcinomas, papillary thyroid cancer, malignant
      melanoma, and hairy cell leukemia (HCL). Malignant melanoma and HCL are of
      particular interest because of both the high proportion of cases harboring the
      mutation and the dramatic responses to BRAF inhibitor therapy reported in the
      literature. This report presents a patient with HCL and malignant melanoma with
      the BRAF p.V600E mutation, and discusses the successful treatment of both cancers
      with the BRAF inhibitor dabrafenib. 

PMID- 25583767
TI  - Lung cancer screening, version 1.2015: featured updates to the NCCN guidelines.
AB  - The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung
      Cancer Screening provide recommendations for selecting individuals for lung
      cancer screening, and for evaluation and follow-up of nodules found during
      screening, and are intended to assist with clinical and shared decision-making.
      These NCCN Guidelines Insights focus on the major updates to the 2015 NCCN
      Guidelines for Lung Cancer Screening, which include a revision to the
      recommendation from category 2B to 2A for one of the high-risk groups eligible
      for lung cancer screening. For low-dose CT of the lung, the recommended slice
      width was revised in the table on "Low-Dose Computed Tomography Acquisition,
      Storage, Interpretation, and Nodule Reporting." 

PMID- 25583766
TI  - Identification of a novel fusion gene, IRF2BP2-RARA, in acute promyelocytic
      leukemia.
AB  - Acute promyelocytic leukemia (APL) is characterized by the fusion of retinoic
      acid receptor alpha (RARA) with promyelocytic leukemia (PML) or, rarely, other
      gene partners. This report presents a patient with APL with a novel fusion
      between RARA and the interferon regulatory factor 2 binding protein 2 (IRF2BP2)
      genes. A bone marrow examination in a 19-year-old woman who presented with
      ecchymoses and epistaxis showed morphologic and immunophenotypic features
      consistent with APL. PML oncogenic domain antibody was positive. Results of
      fluorescence in situ hybridization, conventional cytogenetics, reverse
      transcription-polymerase chain reaction (RT-PCR), and oligonucleotide microarray
      for PML-RARA and common APL variant translocations were negative. Next-generation
      RNA-sequencing analysis followed by RT-PCR and direct sequencing revealed
      distinct breakpoints within IRF2BP2 exon 2 and RARA intron 2. The patient
      received all-trans retinoic acid, arsenic, and gemtuzumab ozogamicin, and
      achieved complete remission. However, the disease relapsed 10 months later, 2
      months after consolidation therapy. This is the first report showing involvement
      of IRF2BP2 in APL, and it expands the list of novel RARA partners identified in
      APL. 

PMID- 25583769
TI  - Predictors of guideline treatment nonadherence and the impact on survival in
      patients with colorectal cancer.
AB  - BACKGROUND: This study investigated the effect of comorbidity, age, health
      insurance payer status, and race on the risk of patient nonadherence to NCCN
      Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon and Rectal
      Cancers. In addition, the prognostic impact of NCCN treatment nonadherence on
      overall survival was assessed. PATIENTS AND METHODS: Patients with CRC who
      received primary treatment at Memorial University Medical Center from 2003 to
      2010 were eligible for this study. Modified Poisson regression was used to obtain
      risk ratios for the outcome of nonadherence with NCCN Guidelines. Hazard ratios
      (HRs) for the relative risk of death from all causes were obtained through Cox
      regression. RESULTS: Guideline-adherent treatment was received by 82.7% of
      patients. Moderate/severe comorbidity, being uninsured, having rectal cancer,
      older age, and increasing tumor stage were associated with increased risks of
      receiving nonadherent treatment. Treatment nonadherence was associated with 3.6
      times the risk of death (HR, 3.55; 95% CI, 2.16-5.85) in the first year after
      diagnosis and an 80% increased risk of death (HR, 1.80; 95% CI, 1.14-2.83) in
      years 2 to 5. The detrimental effect of nonadherence declined with increasing
      comorbidity and varied according to age. CONCLUSIONS: Although medically
      justifiable reasons exist for deviating from NCCN Guidelines when treating
      patients with colorectal cancer (CRC), those who received nonadherent treatment
      had much higher risks of death, especially in the first year after diagnosis.
      This study's results highlight the importance of cancer health services research
      to drive quality improvement efforts in cancer care for patients with CRC.

PMID- 25583768
TI  - Effect of hepatitis C virus infection in patients with cancer: addressing a
      neglected population.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is a neglected disease in patients
      with cancer. Therefore, this study examined the impact of HCV infections in these
      patients. METHODS: The records of HCV-infected patients with cancer seen at The
      University of Texas MD Anderson Cancer Center (2008-2011) were reviewed. The
      outcomes of those who underwent HCV treatment were analyzed. RESULTS: Of 1291
      patients who had positive test results for an antibody to HCV (anti-HCV), 744
      (58%) were tested for HCV-RNA; 642 (86%) of which had chronic HCV infections.
      Most had solid tumors (72%) and genotype-1 (G-1) infections (66%). HCV therapy
      was administered in 348 patients (98 of them after cancer diagnosis). Sustained
      virologic response (SVR) occurred in 27 (35%) of the 78 patients treated for whom
      outcome data were available. Compared with patients who experienced an SVR, more
      patients who did not were black (29% vs 4%; P=.007), had G-1 infections (72% vs
      6%; P<.0001), and had higher baseline aspartate aminotransferase (78 vs 47 IU/L;
      P=.006) and alanine aminotransferase levels (71.1 vs 43.3 IU/L; P=.009). Overall,
      progression to cirrhosis (hazard ratio [HR], 0.38; P=.03) and portal hypertension
      (HR, 0.19; P=.009) was less common in those treated, irrespective of the
      treatment outcome (SVR or non-SVR). Hepatocellular carcinoma (HCC) developed as a
      second primary malignancy in 7% of patients with non-HCC cancer. CONCLUSIONS:
      This is the largest series to analyze HCV infections in patients with cancer. HCV
      therapy is feasible and prevents liver disease progression in this forgotten
      population. A treatment algorithm is provided.

PMID- 25583770
TI  - Cost implications and complications of overtreatment of low-risk prostate cancer
      in the United States.
AB  - BACKGROUND: Evidence-based consensus guidelines recommend only observation for
      men with low-risk prostate cancer and life expectancy less than 10 years. This
      report describes the incidence, drivers, cost, and morbidity of overtreatment of
      low-risk prostate cancer within the United States. METHODS: The SEER-Medicare
      Program was used to identify 11,744 men aged 66 years or older diagnosed with low
      risk prostate cancer in 2004 through 2007. Overtreatment of prostate cancer was
      defined as definitive treatment of a patient with a life expectancy of less than
      10 years. Expected survival was estimated using NCCN methodology. Costs were the
      amount paid by Medicare in years after minus year before diagnosis. Toxicities
      were relevant Medicare diagnoses/interventions. P values are 2-sided. RESULTS: Of
      3001 men with low-risk prostate cancer and a life expectancy of less than 10
      years, 2011 men (67%) were overtreated. On multivariable logistic regression,
      overtreated men were more likely to be married (odds ratio [OR], 1.29; 95% CI,
      1.05-1.59; P=.02), reside in affluent regions (P<.001), and harbor more advanced
      disease at diagnosis (P<.001). Two-year toxicity was greater in overtreated
      patients (P<.001). Relative to active surveillance/watchful waiting/observation,
      the median additional cost per definitive treatment was $18,827 over 5 years; the
      cumulative annual cost attributable to overtreatment in the United States was
      $58.7 million. The ability to avoid treating the 80% of men with low-grade
      disease who will never die of prostate cancer would save $1.32 billion per year
      nationally. CONCLUSIONS: Overtreatment of low-risk prostate cancer is partially
      driven by sociodemographic factors and occurs frequently, with marked impact on
      patient quality of life and health-related costs.

PMID- 25583771
TI  - Guideline familiarity predicts variation in self-reported use of routine
      surveillance PET/CT by physicians who treat head and neck cancer.
AB  - BACKGROUND: Use of routine surveillance testing beyond guideline recommended
      levels is common in many oncologic disciplines, including head and neck cancer.
      The impact of guideline familiarity and other physician characteristics on
      surveillance imaging use are not well understood. METHODS: A cross-sectional
      national survey was performed of physicians responsible for surveillance of
      patients with head and neck squamous cell carcinoma (HNSCC). The primary outcome
      was self-reported use of routine surveillance PET/CT in asymptomatic patients. A
      secondary outcome was familiarity with guideline recommendations. Using
      multivariable regression, the impact of guideline familiarity and other physician
      characteristics on PET/CT use was examined. RESULTS: Of the 502 responders, 79%
      endorsed ever using PET/CT scans for routine surveillance imaging, and 39% were
      high imaging users (used PET/CT scans on more than half of their asymptomatic
      patients); 76% were familiar with the NCCN Clinical Practice Guidelines in
      Oncology for Head and Neck Cancers recommending against routine surveillance
      PET/CT scans. Although guideline familiarity was associated with being a low
      imaging user or a never-user, among those who were familiar with guidelines, 31%
      were nonetheless high imaging users and 73% endorsed ever using PET/CT scans. In
      multivariable analysis controlling for physician characteristics, guideline
      familiarity was the strongest predictor of PET/CT use. CONCLUSIONS: Familiarity
      with the NCCN Guidelines predicts self-reported routine surveillance PET/CT use
      among physicians who treat patients with HNSCC. However, given the observed
      variation and high levels of imaging even among physicians who are familiar with
      the guidelines, further research should examine the reasons physicians choose to
      use surveillance PET/CT scans.

PMID- 25583772
TI  - Neuroendocrine tumors, version 1.2015.
AB  - Neuroendocrine tumors (NETs) comprise a broad family of tumors that may or may
      not be associated with symptoms attributable to hormonal hypersecretion. The NCCN
      Clinical Practice Guidelines in Oncology for Neuroendocrine Tumors discuss the
      diagnosis and management of both sporadic and hereditary NETs. This selection
      from the guidelines focuses on sporadic NETs of the pancreas, gastrointestinal
      tract, lung, and thymus. 

PMID- 25583773
TI  - Role of somatostatin analogues in the treatment of neuroendocrine tumors.
AB  - Neuroendocrine tumors (NETs) are rare epithelial neoplasms with neuroendocrine
      differentiation that most commonly originate in the lungs and gastrointestinal
      tract. Many patients have advanced disease not amenable to surgery or local
      management. Some tumors also secrete amines, such as serotonin, that lead to
      syndromes of hormone excess, such as diarrhea and flushing. Thus, management of
      patients with NETs often requires a dual approach, including hormone symptom
      management and systemic tumor control. Somatostatin analogues have long been a
      mainstay of managing the hormone-related symptoms, and increasing evidence also
      supports their use for tumor control in patients with well-differentiated NETs.
      This article reviews the role of somatostatin analogues in the treatment of NETs.

PMID- 25583774
TI  - Paving the road to clinical trial participation: removing road blocks and
      directing patients toward novel therapies.

PMID- 25583775
TI  - Management of chemotherapy-induced neutropenia: measuring quality, cost, and
      value.
AB  - Treatment-associated neutropenia continues to represent the most common dose
      limiting toxicity of cancer chemotherapy. It often leads to fever and infection,
      prompting hospitalization and occasionally resulting in serious morbidity, and
      even mortality, despite modern broad-spectrum antibiotic treatment and supportive
      care. Neutropenia and its complications may also lead to chemotherapy dose
      reductions, treatment delays, or early treatment termination, compromising
      disease control and the potential for cure. NCCN Clinical Practice Guidelines in
      Oncology recommend administration of primary prophylaxis with a myeloid growth
      factor in patients receiving regimens associated with a high risk for febrile
      neutropenia, and consideration of prophylaxis in patients receiving lower-risk
      regimens who have other risk factors that might place them at higher risk for
      febrile neutropenia. Although these agents have been shown to be effective and
      safe in numerous randomized controlled trials, they are expensive and contribute
      significantly to increasing health care costs. Regulatory agencies and guideline
      organizations do not currently address the issue of cost. However, with the
      relentless increase in health care use and current efforts to reform health care,
      it has become increasingly important to assess both the cost and the net benefit
      of interventions related to an episode of care in order to compare the overall
      value of therapeutic options. This article defines and discusses the intersection
      of quality, costs, and value in the context of prophylactic myeloid growth factor
      use in patients with cancer receiving myelosuppressive chemotherapy. 

PMID- 25583780
TI  - Immunotherapy toxic in obese mice.
AB  - New research shows immunotherapy can cause lethal inflammation in both young and
      aged mice that are obese. Restricting calories in aged mice protected them from
      toxicity, and giving young obese mice a drug for autoimmune disease prevented the
      fatal reactions. 

PMID- 25583779
TI  - IDH1 inhibitor shows promising early results.
AB  - The experimental drug AG-120, which inhibits mutant IDH1, showed promising
      results in a phase I trial in patients with relapsed or refractory acute myeloid
      leukemia. 

PMID- 25583781
TI  - TCGA finds thyroid cancer drivers, subtypes.
AB  - An analysis of thyroid cancer by The Cancer Genome Atlas Research Network
      identifies previously unknown molecular subtypes of thyroid cancer, potentially
      leading to more accurate diagnosis and targeted treatments. 

PMID- 25583782
TI  - Study uncovers mutation involved in two cancers.
AB  - A new study suggests that RNF43 is one of the most commonly mutated genes in
      endometrial and colorectal cancers and may help identify patients who could
      potentially benefit from drugs that target the Wnt signaling pathway. 

PMID- 25583785
TI  - Cancer-killing CAR therapies gain speed.
AB  - In recent clinical trials, engineered CAR T cells have yielded response rates as
      high as 90% in patients with leukemia. Now, scientists are working to get this
      therapy to market and possibly expand its use into solid tumors. 

PMID- 25583786
TI  - In search of exceptional responders.
AB  - A new NCI initiative aims to accrue and molecularly profile as many as 300 cases
      of exceptional responses to cancer therapies, both targeted and standard.
      Researchers hope this exercise will yield new hypotheses to be tested in
      genomically driven clinical trials. 

PMID- 25583797
TI  - Addressing the controversy: do bisphosphonates directly affect primary tumors?
AB  - The recent article by Junankar and colleagues focuses on demonstrating the uptake
      of bisphosphonates (BP) into the primary tumor in both animal models and human
      samples. Interestingly, the authors were able to establish tumor-associated
      macrophages as the cell type that takes up the BPs. These studies are an
      important advancement for understanding the potential benefits of using BPs as
      adjuvant therapy in patients with cancer.

PMID- 25583798
TI  - The microsatellite instable subset of colorectal cancer is a particularly good
      candidate for checkpoint blockade immunotherapy.
AB  - The microsatellite instable (MSI) subset of colorectal cancer exhibits an active
      Th1/CTL immune microenvironment, probably due to recognition of a high number of
      tumor neoantigens. However, the high expression of checkpoint molecules PD-1, PD
      L1, CTLA-4, LAG-3, and IDO in MSI colorectal cancer distinguishes MSI from
      microsatellite stable colorectal cancer and creates an immunosuppressive
      microenvironment that may help MSI tumors evade immune destruction by the
      infiltrating immune cells. Though colorectal cancer does not have a good response
      rate to PD-1 pathway immunotherapy, these results suggest that the MSI subset of
      colorectal cancer is a particularly good candidate for checkpoint immunotherapy.

PMID- 25583799
TI  - Turning telomerase into a Jekyll and Hyde case?
AB  - It may be possible to coerce telomerase to incorporate modified guanine
      nucleotides into telomeric repeat DNA, thereby seriously compromising the
      functionality of the telomeres. Thus, a guanine analogue such as 6-thio-dG could
      turn active telomerase into a chromosome de-protecting enzyme, the opposite of
      what it is normally, namely a chromosome-protecting enzyme.

PMID- 25583801
TI  - Screening strategy may help overcome resistance.
AB  - A new screening platform that uses cells grown from patients' own tumor biopsies
      may offer a way to rapidly identify drug combinations capable of overcoming
      resistance to treatment. 

PMID- 25583800
TI  - How does multistep tumorigenesis really proceed?
AB  - Identifying the cancer cells-of-origin is of great interest, as it holds the
      potential to elucidate biologic mechanisms inherent in the normal cell state that
      have been co-opted to drive the oncogenic cell state. An emerging concept,
      proposed here, states that cancer stem cells, key players in cancer initiation
      and metastasis, arise when transit-amplifying cells with mutant genomes
      dedifferentiate and enter the stem cell state. This model contrasts with the
      notion that cancer stem cells are the direct products of neoplastically
      transformed normal tissue stem cells.

PMID- 25583812
TI  - Making sure ADCs don't go astray.
AB  - Researchers are looking to improve the design and delivery of antibody-drug
      conjugates by studying how they interact with and are influenced by the
      mononuclear phagocyte system. 

PMID- 25583815
TI  - Olaparib effective in four advanced cancers.
AB  - In a phase II study, researchers found that the PARP inhibitor olaparib led to
      stable disease or tumor regressions in patients with advanced breast, ovarian,
      pancreatic, and prostate cancers who had germline mutations in BRCA1 or BRCA2. 

PMID- 25583816
TI  - Gefitinib extends survival in some esophageal cancers.
AB  - Findings from the phase III TRANS-COG clinical trial suggest that the EGFR
      inhibitor gefitinib may extend overall survival in patients with esophageal
      cancer whose tumors have extra copies of EGFR. 

PMID- 25583817
TI  - "C dots" appear safe for use in humans.
AB  - A new study demonstrates for the first time that a nanoparticle-based imaging
      technology known as C dots is safe for human use and may be a more effective
      method of detecting tumors than traditional radiotracers. 

PMID- 25583818
TI  - Helping CAR T cells reach tumors.
AB  - CAR T cells have shown dramatic effects against blood cancers, but they have had
      little impact on solid tumors. Researchers increased the effectiveness of CAR T
      cell therapy in solid tumors by injecting the cells near the tumors. A phase I
      trial using this approach will begin early next year. 

PMID- 25583819
TI  - Chemotherapy helps overcome trastuzumab resistance.
AB  - Thought to be resistant to trastuzumab, the p95HER2 subtype of HER2-positive
      breast cancer responds to the drug when it's given in combination with
      chemotherapy, according to results of a recent study. 

PMID- 25583820
TI  - Novel molecule targets cytokinesis.
AB  - Researchers have identified a new compound, OTS964, that blocks cytokinesis.
      Injections of the compound eliminated human lung tumors that had been
      transplanted into mice. Clinical trials of OTS964 may start next year. 

PMID- 25583821
TI  - Some dendritic cells active inside tumors.
AB  - Macrophages within tumors quell immune attacks on the cancer cells, but a new
      study shows that tumors also contain a small number of CD103+ dendritic cells
      that activate antitumor CD8+ T cells. The dendritic cells help shrink tumors in
      mouse models, and their presence might serve as a prognostic biomarker-and
      improve the odds of survival for patients. 

PMID- 25583823
TI  - Influence of a publication rotation in a neurology residency program in a
      developing country.

PMID- 25583822
TI  - Hyaluronan synthase assembles chitin oligomers with -GlcNAc(alpha1->)UDP at the
      reducing end.
AB  - Class I hyaluronan synthases (HASs) assemble a polysaccharide containing the
      repeating disaccharide [GlcNAc(beta1,4)GlcUA(beta1,3)]n-UDP and vertebrate HASs
      also assemble (GlcNAc-beta1,4)n homo-oligomers (chitin) in the absence of GlcUA
      UDP. This multi-membrane domain CAZy GT2 family glycosyltransferase, which
      couples HA synthesis and translocation across the cell membrane, is atypical in
      that monosaccharides are incrementally assembled at the reducing, rather than the
      non-reducing, end of the growing polymer. Using Escherichia coli membranes
      containing recombinant Streptococcus equisimilis HAS, we demonstrate that a
      prokaryotic Class I HAS also synthesizes chitin oligomers (up to 15-mers, based
      on MS and MS/MS analyses of permethylated products). Furthermore, chitin
      oligomers were found attached at their reducing end to -4GlcNAc(alpha1->)UDP
      [i.e. (GlcNAcbeta1,4)nGlcNAc(alpha1->)UDP]. These oligomers, which contained up
      to at least seven HexNAc residues, consisted of beta4-linked GlcNAc residues,
      based on the sensitivity of the native products to jack bean beta-N
      acetylhexosaminidase. Interestingly, these oligomers exhibited mass defects of 
      2, or -4 for longer oligomers, that strictly depended on conjugation to UDP, but
      MS/MS analyses indicate that these species result from chemical dehydrogenations
      occurring in the gas phase. Identification of (GlcNAc-beta1,4)n-GlcNAc(alpha1
      >)UDP as HAS reaction products, made in the presence of GlcNAc(alpha1->)UDP only,
      provides strong independent confirmation for the reducing terminal addition
      mechanism. We conclude that chitin oligomer products made by HAS are derived from
      the cleavage of these novel activated oligo-chitosyl-UDP oligomers. Furthermore,
      it is possible that these UDP-activated chitin oligomers could serve as self
      assembled primers for initiating HA synthesis and ultimately modify the non
      reducing terminus of HA with a chitin cap. 

PMID- 25583825
TI  - MRI in X-linked adrenoleukodystrophy.

PMID- 25583824
TI  - Quality improvement in neurology: primary headache quality measures.

PMID- 25583826
TI  - Excessive brain iron accumulation in spinocerebellar ataxia type 17.

PMID- 25583827
TI  - Neuromuscular junction as Achilles' heel: yet another autoantibody?

PMID- 25583828
TI  - FLAIR vascular hyperintensity resolution in a TIA patient: clinical-radiologic
      correlation.

PMID- 25583829
TI  - Midlife personality and risk of Alzheimer disease and distress: A 38-year follow
      up.

PMID- 25583830
TI  - Teaching NeuroImages: Striatocapsular infarct presumed due to intracranial
      lipoma.

PMID- 25583831
TI  - Teaching NeuroImages: Meningioangiomatosis.

PMID- 25583834
TI  - Any evident MRI T2 lesion activity should guide change of therapy in multiple
      sclerosis: no.

PMID- 25583833
TI  - What drives MRI-measured cortical atrophy in multiple sclerosis?
AB  - BACKGROUND: Cortical atrophy, assessed with magnetic resonance imaging (MRI), is
      an important outcome measure in multiple sclerosis (MS) studies. However, the
      underlying histopathology of cortical volume measures is unknown. OBJECTIVE: We
      investigated the histopathological substrate of MRI-measured cortical volume in
      MS using combined post-mortem imaging and histopathology. METHODS: MS brain
      donors underwent post-mortem whole-brain in-situ MRI imaging. After MRI, tissue
      blocks were systematically sampled from the superior and inferior frontal gyrus,
      anterior cingulate gyrus, inferior parietal lobule, and superior temporal gyrus.
      Histopathological markers included neuronal, axonal, synapse, astrocyte,
      dendrite, myelin, and oligodendrocyte densities. Matched cortical volumes from
      the aforementioned anatomical regions were measured on the MRI, and used as
      outcomes in a nested prediction model. RESULTS: Forty-five tissue blocks were
      sampled from 11 MS brain donors. Mean age at death was 68+/-12 years, post-mortem
      interval 4+/-1 hours, and disease duration 35+/-15 years. MRI-measured regional
      cortical volumes varied depending on anatomical region. Neuronal density,
      neuronal size, and axonal density were significant predictors of GM volume.
      CONCLUSIONS: In patients with long-standing disease, neuronal and axonal
      pathology are the predominant pathological substrates of MRI-measured cortical
      volume in chronic MS.

PMID- 25583835
TI  - Female infertility and multiple sclerosis: is this an issue?

PMID- 25583832
TI  - Long-term safety and efficacy of dalfampridine for walking impairment in patients
      with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical
      trials.
AB  - BACKGROUND: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine
      extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release
      fampridine in Europe; fampridine modified or sustained release elsewhere)
      improved walking speed relative to placebo in patients with multiple sclerosis
      (MS). OBJECTIVES: Evaluation of long-term safety and efficacy of dalfampridine-ER
      in open-label extensions (MS-F203EXT, MS-F204EXT). METHODS: Patients received
      dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW)
      assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were
      categorized as dalfampridine-ER responders or non-responders, based on their
      treatment response in the double-blind parent trials that assessed T25FW.
      RESULTS: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a
      maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146
      complete it; for a maximum exposure of 3.3 years. No new safety signals emerged
      and dalfampridine-ER tolerability was consistent with the double-blind phase.
      Improvements in walking speed were lost after dalfampridine-ER was discontinued
      in the parent trial, but returned by the 2-week assessment after re-initiation of
      the drug. Throughout the extensions, mean improvement in walking speed declined,
      but remained improved, among the double-blind responders as compared with non
      responders. CONCLUSIONS: The dalfamipridine-ER safety profile was consistent with
      the parent trials. Although walking speed decreased over time, dalfampridine-ER
      responders continued to show improved walking speed, which was sustained compared
      with non-responders.

PMID- 25583836
TI  - Lending a hand: can DASH items help ABILHAND improve manual ability measurement
      in multiple sclerosis?
AB  - BACKGROUND: Our examination in multiple sclerosis (MS) of the ABILHAND, a patient
      reported outcome (PRO) instrument measuring manual ability, identified limited
      measurement range and precision. These deficiencies could lead to type II errors
      in clinical trials. OBJECTIVES: This paper aims to determine if ABILHAND's
      measurement performance in MS can be improved by adding relevant items from the
      Disabilities of the Arm, Shoulder and Hand scale (DASH). METHODS: The 23-item
      ABILHAND and 30-item DASH were administered to 461 people with MS. Data from the
      ABILHAND were combined with 16 DASH items to create a 39-item scale (AD-39).
      Using Rasch Measurement Theory methods, we compared the psychometric properties
      of AD-39 with ABILHAND. RESULTS: Data were analysed from 300 people. AD-39
      performed robustly as a measure and had greater measurement range, lower floor
      and ceiling effects, and higher reliability (person separation index 0.97) than
      ABILHAND. Surprisingly, AD-39 appeared no better than ABILHAND at detecting group
      differences in self-reported hand function. CONCLUSION: Despite improving some
      psychometric properties, adding 16 DASH items to the ABILHAND did not improve its
      measurement performance to the degree expected. Our explanations for this anomaly
      emphasise the importance of evidence-based, conceptually driven scale
      modifications guided by hypothesis testing psychometric methods.

PMID- 25583837
TI  - High-dose methylprednisolone for multiple sclerosis during lactation:
      Concentrations in breast milk.

PMID- 25583838
TI  - Low intensity lympho-ablative regimen followed by autologous hematopoietic stem
      cell transplantation in severe forms of multiple sclerosis: A MRI-based clinical
      study.
AB  - BACKGROUND: Autologous hematopoietic stem cell transplantation (AHSCT) has been
      successfully used to treat aggressive forms of multiple sclerosis (MS) that are
      unresponsive to approved therapies. In the last years, in view of the risk of
      mortality related to the procedure, the utilization of low-intensity conditioning
      regimens has been considered. OBJECTIVE: To report magnetic resonance imaging
      (MRI) and clinical data in a small cohort of patients treated with a low
      intensity lympho-ablative regimen, followed by AHSCT. METHODS: Seven patients
      affected by relapsing-remitting MS (RRMS) underwent AHSCT, with cyclophosphamide
      120 mg/kg in 2 days as the conditioning regimen; and were then followed with
      serial MRI evaluations until 36 months, with clinical evaluations until 60
      months. RESULTS: The mean number of gadolinium (Gd)-enhancing lesions
      significantly decreased after treatment, but a complete suppression of
      inflammatory activity was not obtained. No deaths occurred, but every patient
      developed adverse events, although not severe. After 5 years of follow-up, two
      patients remained stable, one patient markedly improved and four patients had a
      mild progression of the disease. Only one patient experienced a relapse after
      treatment. CONCLUSION: A low-intensity conditioning regimen with AHSCT has a
      profound effect on MRI inflammation and relapses, but is not able to completely
      abrogate MRI activity and disease progression of aggressive RRMS.

PMID- 25583840
TI  - MS in prose, poems and drama.
AB  - BACKGROUND AND OBJECTIVE: Presentations of MS in fictional literature have not
      been previously researched. This paper surveys and analyses these portrayals of
      the disease for the first time. MATERIAL AND METHODS: Relevant works in English
      and German were identified by means of keyword searches in online public access
      catalogues and search engines as well as old-fashioned research. The neurological
      and literary evaluation of these 7000 pages of text combines qualitative and
      quantitative methods. RESULTS: Between 1954 and 2012 at least 55 literary works
      appeared with an MS motif (35 novels, 18 poems, one novella and one drama). The
      authors were predominantly female and a third of them suffered from the disease.
      Patients in the novels largely reflect real epidemiology as regards symptoms and
      disease progression, while diagnostic and therapeutic options play a secondary
      role. From a literary point of view, 'entwicklungsromane', 'relationship novels'
      and 'young adult books' can be discerned. MS is often portrayed in metaphoric
      language as the enemy: a demon, an animalistic being, prison or an abyss.
      CONCLUSION: The MS motif evidences a medicalization of the literature as well as
      a literary portrayal of anthropological experiences. Well-written novels can
      contribute to the de-stigmatization of MS and impart basic medical knowledge.

PMID- 25583839
TI  - Analysis of genes, pathways and networks involved in disease severity and age at
      onset in primary-progressive multiple sclerosis.
AB  - BACKGROUND: The role of genetic factors in influencing the clinical expression of
      multiple sclerosis (MS) is unclear. OBJECTIVE: The objective of this paper is to
      identify genes, pathways and networks implicated in age at onset (AAO) and
      severity, measured using the Multiple Sclerosis Severity Score (MSSS), of primary
      progressive MS (PPMS). METHODS: We conducted a genome-wide association study
      (GWAS) of 470 PPMS patients of Italian origin:. Allelic association of 296,589
      SNPs with AAO and MSSS was calculated. Pathway and network analyses were also
      conducted using different tools. RESULTS: No single association signal exceeded
      genome-wide significance in AAO and MSSS analyses. Nominally associated genes to
      AAO and MSSS were enriched in both traits for 10 pathways, including: "oxidative
      phosphorylation" (FDRAAO=9*10(-4); FDRMSSS=3.0*10(-2)), "citrate (TCA) cycle"
      (FDRAAO=1.6*10(-2); FDRMSSS=3.2*10(-3)), and "B cell receptor signaling"
      (FDRAAO=3.1*10(-2); FDRMSSS=2.2*10(-3)). In addition, an enrichment of "chemokine
      signaling pathway" (FDR=9*10(-4)) for AAO and of "leukocyte transendothelial
      migration" (FDR=2.4*10(-3)) for MSSS trait was observed, among others. Network
      analysis revealed that p53 and CREB1 were central hubs for AAO and MSSS traits,
      respectively. CONCLUSIONS: Despite the fact that no major effect signals emerged
      in the present GWAS, our data suggest that genetic variants acting in the context
      of oxidative stress and immune dysfunction could modulate the onset and severity
      of PPMS.

PMID- 25583841
TI  - Subclinical central inflammation is risk for RIS and CIS conversion to MS.
AB  - BACKGROUND: Subtle diffuse intrathecal inflammation is undetectable by
      conventional neuroimaging, and could influence multiple sclerosis (MS) disease
      course. OBJECTIVE: To explore the role of subclinical persisting intrathecal
      inflammation in radiologically isolated syndrome (RIS) or clinically isolated
      syndrome (CIS) conversion to MS, and in early MS disease reactivation. METHODS:
      One-hundred ninety-three subjects with RIS, CIS, relapsing-remitting (RR), or
      primary progressive (PP) MS were included, along with 76 matched controls.
      Cerebrospinal fluid (CSF) levels of interleukin-8 (IL-8), a major proinflammatory
      cytokine, were measured as a biomarker of intrathecal inflammation. Patients were
      followed up for 2 years. Clinical and imaging measures of disease progression
      were recorded. RESULTS: High central contents of IL-8 were associated to clinical
      progression in subjects with RIS, and to the risk of conversion to MS in subjects
      with CIS. Asymptomatic intrathecal inflammation placed subjects at risk for MS
      conversion, even regardless lesion load. CSF IL-8 levels were higher in RR MS
      with high disease activity. Higher number of relapses in the first two years
      since diagnosis and shorter first inter-attack intervals were observed in
      patients with high levels of IL-8. CONCLUSION: IL-8 might provide utility in
      determining the presence of active intrathecal inflammation, and could be
      important in diagnostically undefined cases.

PMID- 25583842
TI  - Remote cognitive assessments for patients with multiple sclerosis: a feasibility
      study.
AB  - BACKGROUND: measuring cognitive function in patients with multiple sclerosis (MS)
      can be challenging given the obstacles faced when traveling to testing centers.
      OBJECTIVE: the purpose of this study was to evaluate the feasibility of remote
      cognitive assessment in patients with MS using the automated neuropsychological
      assessment metrics (ANAM-MS) and the symbol digit modalities test (SDMT).
      METHODS: patients meeting the McDonald criteria for MS (n = 24) were randomized
      to complete the live-in-office condition or a remote-in-office condition first,
      with all patients completing both sessions. Patients (n = 20) then completed a
      final remote-in-home testing session. Both remote sessions were proctored by a
      psychologist using a secure telehealth connection. RESULTS: scores on the live
      SDMT differed from scores in the two remote settings F(2, 38) = 4.46, p = 0.018.
      However, summary scores on the ANAM-MS were similar across the three settings,
      F(2, 36) = 2.21, p = 0.124. Satisfaction with telehealth testing was high on the
      part of the examiner and patients. Each telehealth testing session saved more
      than $144.00 in travel costs and lost wages. CONCLUSION: this study demonstrated
      that valid results can be obtained when evaluating patients remotely using ANAM
      MS. Some differences were noted for the SDMT that suggest that either specific
      norms or a different implementation approach may be needed for telehealth.

PMID- 25583843
TI  - Impact of parental multiple sclerosis on early childhood development: A
      retrospective cohort study.
AB  - BACKGROUND: Exposure to parental chronic illness is associated with several
      adverse developmental outcomes. OBJECTIVES: We examined the association between
      parental multiple sclerosis (MS) and childhood developmental outcomes. METHODS:
      We conducted a population-based retrospective cohort study in Manitoba, Canada,
      using linked databases. The outcome was childhood development at 5 years of age,
      expressed as vulnerability (absent vs. present) on the Early Development
      Instrument (EDI). Logistic regression was used to estimate odds ratios (OR) and
      95% confidence intervals (CI). RESULTS: Children with an MS parent (n=153) were
      similar to children of unaffected parents (n=876) on all EDI domains. However,
      mental health morbidity was more common among MS parents compared with non-MS
      parents 49.5% vs. 35.3%. Among MS parents, mental health morbidity was associated
      with children's vulnerability on the social competence (OR, 5.73 [95% CI:1.11
      29.58]) and emotional maturity (OR, 3.03 [95% CI:1.03-8.94]) domains. The
      duration of child's exposure to parental MS was associated with vulnerability on
      the physical health domain (OR, 1.49 [95%CI:1.03-2.15]). CONCLUSION: Parental MS
      was not associated with adverse early childhood developmental outcomes. However,
      children of parents with mental health morbidity, and those with longer duration
      of exposure to parental MS, were at higher risk for early childhood developmental
      vulnerability.

PMID- 25583844
TI  - Latitude and HLA-DRB1 alleles independently affect the emergence of cerebrospinal
      fluid IgG abnormality in multiple sclerosis.
AB  - BACKGROUND: It is unclear whether the prevalence of oligoclonal IgG bands (OCBs)
      in multiple sclerosis (MS) is different between northern and southern regions of
      Asia. OBJECTIVE: This study aimed to compare the prevalence of OCBs and positive
      cerebrospinal fluid (CSF) findings between northern and southern regions of Japan
      and to investigate the association of these CSF findings with HLA-DRB1 alleles.
      METHODS: The study included 180 MS patients from Hokkaido (northern Japan) and
      184 patients from Kyushu (southern Japan). The IgG index was defined as increased
      if it was >0.658. Presence of CSF OCBs and/or increased IgG index was defined as
      positive CSF findings. RESULTS: Positive CSF findings and OCB positivity were
      significantly higher in MS patients from Hokkaido than in those from Kyushu (p <
      0.0001 for both). Logistic regression analysis revealed that after adjusting for
      covariates that can be related to abnormal CSF IgG production, the geographic
      region (Hokkaido) showed odds ratios (ORs) of 4.08 and 2.57, whereas the HLA
      DRB1*04:05 allele showed ORs of 0.36 and 0.30 for positive CSF findings and OCB
      positivity, respectively. CONCLUSIONS: The results indicate that latitude and HLA
      DRB1 alleles independently affect the emergence of CSF IgG abnormalities in
      Japanese patients with MS.

PMID- 25583846
TI  - Validity of four screening scales for major depression in MS.
AB  - BACKGROUND: There is a role for brief assessment instruments in detection and
      management of major depression in MS. However, candidate scales have rarely been
      validated against a validated diagnostic interview. In this study, we evaluated
      the performance of several candidate scales: Patient Health Questionnaire (PHQ)
      9, PHQ-2, Center for Epidemiologic Studies Depression rating scale (CES-D), and
      Hospital Anxiety and Depression Scale (HADS-D) in relation to the Structured
      Clinical Interview for DSM-IV (SCID). METHODS: The sample was an unselected
      series of 152 patients attending a multiple sclerosis (MS) clinic. Participants
      completed the scales during a clinic visit or returned them by mail. The SCID was
      administered by telephone within two weeks. The diagnosis of major depressive
      episode, according to the SCID, was used as a reference standard. Receiver
      operator curves (ROC) were fitted and indices of measurement accuracy were
      calculated. RESULTS: All of the scales performed well, each having an area under
      the ROC > 90%. For example, the PHQ-9 had 95% sensitivity and 88.3% specificity
      when scored with a cut-point of 11. This cut-point achieved a 56% positive
      predictive value for major depression. CONCLUSIONS: While all of the scales
      performed well in terms of their sensitivity and specificity, the availability of
      the PHQ-9 in the public domain and its brevity may enhance the feasibility of its
      use.

PMID- 25583847
TI  - Fingolimod does not impair T-cell release from the thymus and beneficially
      affects Treg function in patients with multiple sclerosis.
AB  - BACKGROUND: In multiple sclerosis (MS), disturbed T-cell homeostasis affects both
      conventional CD4(+) T cells (Tcon) and regulatory T cells (Treg). Functionally,
      this is linked to a loss of Treg-suppressive properties. Concerns exist as to
      whether fingolimod might further aggravate Treg dysfunction by inhibiting thymic
      egress and, thus, promoting premature immunosenescence. OBJECTIVE: The objective
      of this paper is to investigate whether fingolimod, by sequestration of
      developing cells in the thymus, might deteriorate numeric and/or functional
      disequilibrium of T-cell subtypes. METHODS: We assessed numbers and phenotypes of
      blood Tcon and Treg in 74 MS patients treated with fingolimod and in 37 healthy
      donors. Treg and Tcon were also analyzed for immunoreactivity, suppressive
      function, sphingosine-1-phosphate-triggered (S1P) trafficking, and S1P-receptor
      expression. This was complemented by assessing surrogate markers of thymic T-cell
      development, including frequencies of cells expressing T-cell receptors (TCR) of
      dual specificity, and TCR diversity in Treg. RESULTS: Fingolimod did not
      negatively affect naive T-cell phenotypes or markers of thymic T-cell
      development. By reducing CCR7-expressing Tcon, fingolimod increased relative
      proportions of Treg. As a result of this shift, fewer proliferative CCR7(-) Tcon
      became enriched and Treg-dysfunction was indirectly reversed. CONCLUSION: These
      observations argue against harmful interference of fingolimod with thymic T-cell
      output that, particularly in pediatric MS, might possibly counteract its
      beneficial effects.

PMID- 25583848
TI  - Twin studies in multiple sclerosis: A meta-estimation of heritability and
      environmentality.
AB  - BACKGROUND: Most twin studies of multiple sclerosis (MS) are inconclusive
      regarding the impact of genes and environment on disease susceptibility. In
      particular, high uncertainty exists about whether shared environmental factors
      are aetiologically relevant. OBJECTIVE: To disentangle, with a reasonable degree
      of confidence, the relative contributions of heritability and of shared and
      unique environmental components of MS susceptibility. METHODS: We performed a
      meta-analysis of previous twin studies. After a MEDLINE search, we selected eight
      twin studies in France, UK, Canada, Denmark, North America, Italy, Finland and
      Sweden. We conducted a biometric multi-group analysis under the liability
      threshold model, by taking account of the study-specific ascertainment strategies
      and the population-specific prevalence rates of MS. RESULTS: The meta-analytic
      estimates of tetrachoric correlations were 0.71 (95% confidence interval (CI):
      0.67-0.74) in monozygotic pairs and 0.46 (95% CI: 0.41-0.50) in dizygotic pairs.
      The biometric multi-group model provided meta-analytic estimates of 0.50 (95% CI:
      0.39-0.61) for heritability, 0.21 (95% CI: 0.11-0.30) for shared environmental
      component and 0.29 (95% CI: 0.26-0.33) for unique environmental component.
      CONCLUSION: Our results support the continuing efforts to identify unknown
      genetic factors that fill the gap of 'missing heritability'; moreover, a 'missing
      environmentality' deserves future investigations into the role of non-heritable
      components that act as both shared and individual-specific exposures.

PMID- 25583845
TI  - The incidence and prevalence of psychiatric disorders in multiple sclerosis: a
      systematic review.
AB  - BACKGROUND: Psychiatric comorbidity is associated with lower quality of life,
      more fatigue, and reduced adherence to disease-modifying therapy in multiple
      sclerosis (MS). OBJECTIVES: The objectives of this review are to estimate the
      incidence and prevalence of selected comorbid psychiatric disorders in MS and
      evaluate the quality of included studies. METHODS: We searched the PubMed,
      PsychInfo, SCOPUS, and Web of Knowledge databases and reference lists of
      retrieved articles. Abstracts were screened for relevance by two independent
      reviewers, followed by full-text review. Data were abstracted by one reviewer,
      and verified by a second reviewer. Study quality was evaluated using a
      standardized tool. For population-based studies we assessed heterogeneity
      quantitatively using the I2 statistic, and conducted meta-analyses. RESULTS: We
      included 118 studies in this review. Among population-based studies, the
      prevalence of anxiety was 21.9% (95% CI: 8.76%-35.0%), while it was 14.8% for
      alcohol abuse, 5.83% for bipolar disorder, 23.7% (95% CI: 17.4%-30.0%) for
      depression, 2.5% for substance abuse, and 4.3% (95% CI: 0%-10.3%) for psychosis.
      CONCLUSION: This review confirms that psychiatric comorbidity, particularly
      depression and anxiety, is common in MS. However, the incidence of psychiatric
      comorbidity remains understudied. Future comparisons across studies would be
      enhanced by developing a consistent approach to measuring psychiatric
      comorbidity, and reporting of age-, sex-, and ethnicity-specific estimates.

PMID- 25583849
TI  - Antibodies to the inward rectifying potassium channel 4.1 in multiple sclerosis:
      different methodologies--conflicting results?

PMID- 25583850
TI  - The changing face of multiple sclerosis: Prevalence and incidence in an aging
      population.
AB  - OBJECTIVE: To assess multiple sclerosis (MS) incidence from 1998 to 2007, and MS
      prevalence on 31 December 2007, in the province of Genoa, Italy. METHODS: We
      identified MS cases diagnosed before 31 December 2007 by analyzing archives of
      hospitals with neurological or rehabilitation wards, the local Italian MS
      society, family doctor records and requests for oligoclonal band analysis on
      cerebrospinal fluid (CSF). RESULTS: A total of 1312 MS patients were residing in
      the province of Genoa on the prevalence day; 431 (32.85%) were men and 881
      (67.15%) were women; mean age was 50.6 (+/- 13.9). The overall crude MS
      prevalence rate was 148.5/100,000; 103.1/100,000 in men and 189.1/100,000 in
      women. The crude mean annual MS incidence rate was 6.6 cases/100,000 (4.4/100,000
      men; 8.6/100,000 women). Mean age at diagnosis was 39.5 +/- 12.3 (men: 39.9 +/-
      13.0; women: 39.3 +/- 11.9). A mean annual incidence of 4 MS patients >= 60 was
      observed. CONCLUSIONS: We observed an increased MS prevalence in the province of
      Genoa, compared to 1997. The mean age at diagnosis was relatively high (39 years
      old), 18% of our MS patients were over 65, and a notable incidence increase was
      seen in patients over 60. This has important implications, in terms of the need
      to organize the health system to better serve elderly MS patients, especially
      considering comorbidities and different medical needs of elderly MS patients; and
      to increase awareness within the medical community about the increasing risk of
      newly-presenting MS in the older population.

PMID- 25583851
TI  - Thalamic lesions in multiple sclerosis by 7T MRI: Clinical implications and
      relationship to cortical pathology.
AB  - OBJECTIVE: Pathology in both cortex and deep gray matter contribute to disability
      in multiple sclerosis (MS). We used the increased signal-to-noise ratio of 7
      tesla (7T) MRI to visualize small lesions within the thalamus and to relate this
      to clinical information and cortical lesions. METHODS: We obtained 7T MRI scans
      on 34 MS cases and 15 healthy volunteers. Thalamic lesion number and volume were
      related to demographic data, clinical disability measures, and lesions in
      cortical gray matter. RESULTS: Thalamic lesions were found in 24/34 of MS cases.
      Two lesion subtypes were noted: discrete, ovoid lesions, and more diffuse
      lesional areas lining the periventricular surface. The number of thalamic lesions
      was greater in progressive MS compared to relapsing-remitting (mean +/-SD, 10.7
      +/-0.7 vs. 3.0 +/-0.7, respectively, p < 0.001). Thalamic lesion burden (count
      and volume) correlated with EDSS score and measures of cortical lesion burden,
      but not with white matter lesion burden or white matter volume. CONCLUSIONS:
      Using 7T MRI allows identification of thalamic lesions in MS, which are
      associated with disability, progressive disease, and cortical lesions. Thalamic
      lesion analysis may be a simpler, more rapid estimate of overall gray matter
      lesion burden in MS.

PMID- 25583852
TI  - Sensory integration balance training in patients with multiple sclerosis: A
      randomized, controlled trial.
AB  - BACKGROUND: Impaired sensory integration contributes to balance disorders in
      patients with multiple sclerosis (MS). OBJECTIVE: The objective of this paper is
      to compare the effects of sensory integration balance training against
      conventional rehabilitation on balance disorders, the level of balance confidence
      perceived, quality of life, fatigue, frequency of falls, and sensory integration
      processing on a large sample of patients with MS. METHODS: This single-blind,
      randomized, controlled trial involved 80 outpatients with MS (EDSS: 1.5-6.0) and
      subjective symptoms of balance disorders. The experimental group (n = 39)
      received specific training to improve central integration of afferent sensory
      inputs; the control group (n = 41) received conventional rehabilitation (15
      treatment sessions of 50 minutes each). Before, after treatment, and at one month
      post-treatment, patients were evaluated by a blinded rater using the Berg Balance
      Scale (BBS), Activities-specific Balance Confidence Scale (ABC), Multiple
      Sclerosis Quality of Life-54, Fatigue Severity Scale (FSS), number of falls and
      the Sensory Organization Balance Test (SOT). RESULTS: The experimental training
      program produced greater improvements than the control group training on the BBS
      (p < 0.001), the FSS (p < 0.002), number of falls (p = 0.002) and SOT (p < 0.05).
      CONCLUSIONS: Specific training to improve central integration of afferent sensory
      inputs may ameliorate balance disorders in patients with MS. Clinical Trial
      Registration (NCT01040117).

PMID- 25583854
TI  - Connexin-related (DFNB1) hearing loss: is routine computed tomography imaging
      necessary?
AB  - OBJECTIVES: Determine if routine computed tomography (CT) imaging is necessary in
      the workup for children with connexin-related (DFNB1) sensorineural hearing loss
      (SNHL). STUDY DESIGN: Case-control retrospective chart and imaging review.
      SETTING: Tertiary care otolaryngology practice. SUBJECTS AND METHODS: High
      resolution temporal bone CT scans of children (n = 21) with DFNB1 SNHL were
      compared to age-matched controls with either conductive hearing loss (CHL, n =
      33) or a nonsyndromic, non-DFNB1 SNHL (n = 33). Sixteen measurements of cochleo
      vestibular structures were recorded. Statistical analysis was performed using a
      repeated analysis of variance model that controlled for both age and gender. Area
      under the curve (AUC) and multidimensional AUC (MAUC) analyses were also
      performed. RESULTS: Overall, no statistically significant differences were found
      between the 3 experimental groups. In addition, comparisons between the DFNB1 and
      CHL groups, DFNB1 and non-DFNB1 SNHL groups, and CHL and non-DFNB1 SNHL groups
      failed to demonstrate any statistically significant differences. AUC and MAUC
      analyses also failed to detect any significant differences between the 3 groups.
      CONCLUSIONS: Patients with DFNB1 SNHL do not have significant anatomic
      differences on temporal bone CT scans when compared to non-DFNB1 SNHL and CHL
      control groups. Based on the above analysis, it is reasonable to avoid routine CT
      imaging of the temporal bones in children with known DFNB1 SNHL unless otherwise
      clinically indicated.

PMID- 25583853
TI  - Outcomes of pressure-induced cranial neuropathies from allergic fungal
      rhinosinusitis.
AB  - OBJECTIVES: Allergic fungal rhinosinusitis (AFRS) may present with significant
      bone erosion of the orbital walls or cranial base. Although proptosis is fairly
      common, cranial neuropathies are rarely reported. The objectives of this study
      are to describe strategies for AFRS-induced neuropathies and evaluate
      ophthalmologic outcomes following endoscopic sinus surgery. STUDY DESIGN: Case
      series with chart review. SETTING: Tertiary referral center. SUBJECT AND METHODS:
      A retrospective review identified 9 patients treated from 2008 to 2014 with AFRS
      induced cranial neuropathies. Data regarding patient demographics, preoperative
      imaging, ophthalmologic symptoms, surgical intervention, histopathologic
      findings, and postoperative sinonasal and ophthalmologic outcomes were recorded.
      RESULTS: Patients with AFRS (average age, 38 years) presented with optic
      neuropathy or abducens nerve palsy. Clinical presentation included unilateral
      visual loss secondary to optic nerve compression (n=5), diplopia from unilateral
      (n=2) or bilateral (n=1) abducens nerve palsy, and bitemporal hemianopsia
      secondary to optic chiasm compression (n=1). On average, the duration of ocular
      symptoms was 17 days. All patients underwent endoscopic surgical decompression of
      the sinuses and oral steroid therapy. Two individuals had an additional optic
      nerve decompression at the time of surgery. Seven patients had complete return of
      nerve function, whereas 2 had partial recovery at an average of 5 weeks following
      surgery. CONCLUSION: Bone erosion of the sphenoid sinus walls by AFRS can lead to
      compression of surrounding neural structures producing cranial neuropathies.
      Identification of these symptoms and prompt surgical decompression and removal of
      disease, along with aggressive medical therapy, provided excellent outcomes in
      the current series of patients.

PMID- 25583856
TI  - A comparison between the dynamics of horizontal and vertical axis offshore
      floating wind turbines.
AB  - The need to further exploit offshore wind resources in deeper waters has led to a
      re-emerging interest in vertical axis wind turbines (VAWTs) for floating
      foundation applications. However, there has been little effort to systematically
      compare VAWTs to the more conventional horizontal axis wind turbine (HAWT). This
      article initiates this comparison based on prime principles, focusing on the
      turbine aerodynamic forces and their impact on the floating wind turbine static
      and dynamic responses. VAWTs generate substantially different aerodynamic forces
      on the support structure, in particular, a potentially lower inclining moment and
      a substantially higher torque than HAWTs. Considering the static stability
      requirements, the advantages of a lower inclining moment, a lower wind turbine
      mass and a lower centre of gravity are illustrated, all of which are exploitable
      to have a less costly support structure. Floating VAWTs experience increased
      motion in the frequency range surrounding the turbine [number of
      blades]*[rotational speed] frequency. For very large VAWTs with slower rotational
      speeds, this frequency range may significantly overlap with the range of wave
      excitation forces. Quantitative considerations are undertaken comparing the
      reference NREL 5 MW HAWT with the NOVA 5 MW VAWT.

PMID- 25583855
TI  - Impact of carbon monoxide/heme oxygenase on hydrogen sulfide/cystathionine-gamma
      lyase pathway in the pathogenesis of allergic rhinitis in guinea pigs.
AB  - OBJECTIVE: The discovery of carbon monoxide (CO) and hydrogen sulfide (H2S) as
      pathogenic signaling molecules in airway-related diseases has led to significant
      insights into the pathophysiologic mechanisms underlying the development of
      allergic rhinitis (AR). The potential crosstalk between CO and H2S signaling
      pathways in AR has not been adequately investigated. This study was performed to
      elucidate the mechanistic relationship between CO and H2S in AR. STUDY DESIGN:
      Experimental prospective animal study. SETTING: Animal laboratory of Tongji
      Hospital, Tongji University, Shanghai, China. SUBJECTS AND METHODS: A well
      established model of AR was used whereby guinea pigs (N=24) were randomly divided
      into 4 treatment groups (n=6 for each group): The first group received ovalbumin
      only; the second group was administered exogenous hemin, a CO-binding
      metalloporphyrin; the third group received zinc protoporphyrin, an inhibitor of
      heme oxygenase-1. A control group was challenged using only saline. Symptoms of
      AR were recorded, and quantitation of plasma CO and H2S levels was performed.
      Expression of heme oxygenase-1 and H2S-generating enzyme cystathionine-gamma
      lyase (CSE) were measured from nasal mucosa. RESULTS: Plasma CO and heme
      oxygenase-1 expression levels of nasal mucosa were significantly increased in the
      AR group compared to controls, whereas H2S concentrations were significantly
      decreased. Exogenous administration of CO exacerbated allergic symptoms,
      resulting in higher levels of both CO and heme oxygenase-1 expression, and a
      further reduction in H2S levels and CSE expression. Zinc protoporphyrin decreased
      CO concentrations and increased levels of both H2S and CSE expression.
      CONCLUSIONS: Results indicated an inverse relationship between H2S levels and CO
      in the pathogenesis of AR.

PMID- 25583857
TI  - An immersed-shell method for modelling fluid-structure interactions.
AB  - The paper presents a novel method for numerically modelling fluid-structure
      interactions. The method consists of solving the fluid-dynamics equations on an
      extended domain, where the computational mesh covers both fluid and solid
      structures. The fluid and solid velocities are relaxed to one another through a
      penalty force. The latter acts on a thin shell surrounding the solid structures.
      Additionally, the shell is represented on the extended domain by a non-zero shell
      concentration field, which is obtained by conservatively mapping the shell mesh
      onto the extended mesh. The paper outlines the theory underpinning this novel
      method, referred to as the immersed-shell approach. It also shows how the
      coupling between a fluid- and a structural-dynamics solver is achieved. At this
      stage, results are shown for cases of fundamental interest. 

PMID- 25583858
TI  - Damage tolerance and structural monitoring for wind turbine blades.
AB  - The paper proposes a methodology for reliable design and maintenance of wind
      turbine rotor blades using a condition monitoring approach and a damage tolerance
      index coupling the material and structure. By improving the understanding of
      material properties that control damage propagation it will be possible to
      combine damage tolerant structural design, monitoring systems, inspection
      techniques and modelling to manage the life cycle of the structures. This will
      allow an efficient operation of the wind turbine in terms of load alleviation,
      limited maintenance and repair leading to a more effective exploitation of
      offshore wind. 

PMID- 25583859
TI  - Unsteady aerodynamic analysis for offshore floating wind turbines under different
      wind conditions.
AB  - A free-vortex wake (FVW) model is developed in this paper to analyse the unsteady
      aerodynamic performance of offshore floating wind turbines. A time-marching
      algorithm of third-order accuracy is applied in the FVW model. Owing to the
      complex floating platform motions, the blade inflow conditions and the positions
      of initial points of vortex filaments, which are different from the fixed wind
      turbine, are modified in the implemented model. A three-dimensional rotational
      effect model and a dynamic stall model are coupled into the FVW model to improve
      the aerodynamic performance prediction in the unsteady conditions. The effects of
      floating platform motions in the simulation model are validated by comparison
      between calculation and experiment for a small-scale rigid test wind turbine
      coupled with a floating tension leg platform (TLP). The dynamic inflow effect
      carried by the FVW method itself is confirmed and the results agree well with the
      experimental data of a pitching transient on another test turbine. Also, the
      flapping moment at the blade root in yaw on the same test turbine is calculated
      and compares well with the experimental data. Then, the aerodynamic performance
      is simulated in a yawed condition of steady wind and in an unyawed condition of
      turbulent wind, respectively, for a large-scale wind turbine coupled with the
      floating TLP motions, demonstrating obvious differences in rotor performance and
      blade loading from the fixed wind turbine. The non-dimensional magnitudes of
      loading changes due to the floating platform motions decrease from the blade root
      to the blade tip. 

PMID- 25583860
TI  - Helical piles: an innovative foundation design option for offshore wind turbines.
AB  - Offshore wind turbines play a key part in the renewable energy strategy in the UK
      and Europe as well as in other parts of the world (for example, China). The
      majority of current developments, certainly in UK waters, have taken place in
      relatively shallow water and close to shore. This limits the scale of the
      engineering to relatively simple structures, such as those using monopile
      foundations, and these have been the most common design to date, in UK waters.
      However, as larger turbines are designed, or they are placed in deeper water, it
      will be necessary to use multi-footing structures such as tripods or jackets. For
      these designs, the tension on the upwind footing becomes the critical design
      condition. Driven pile foundations could be used, as could suction-installed
      foundations. However, in this paper, we present another concept-the use of
      helical pile foundations. These foundations are routinely applied onshore where
      large tension capacities are required. However, for use offshore, a significant
      upscaling of the technology will be needed, particularly of the equipment
      required for installation of the piles. A clear understanding of the relevant
      geotechnical engineering will be needed if this upscaling is to be successful. 

PMID- 25583861
TI  - Dynamic response mitigation of floating wind turbine platforms using tuned liquid
      column dampers.
AB  - In this paper, we experimentally study and compare the effects of three
      combinations of multiple tuned liquid column dampers (MTLCDs) on the dynamic
      performance of a model floating tension-leg platform (TLP) structure in a wave
      basin. The structural stability and safety of the floating structure during
      operation and maintenance is of concern for the performance of a renewable energy
      device that it might be supporting. The dynamic responses of the structure should
      thus be limited for these renewable energy devices to perform as intended. This
      issue is particularly important during the operation of a TLP in extreme weather
      conditions. Tuned liquid column dampers (TLCDs) can use the power of sloshing
      water to reduce surge motions of a floating TLP exposed to wind and waves. This
      paper demonstrates the potential of MTLCDs in reducing dynamic responses of a
      scaled TLP model through an experimental study. The potential of using output
      only statistical markers for monitoring changes in structural conditions is also
      investigated through the application of a delay vector variance (DVV) marker for
      different conditions of control for the experiments. 

PMID- 25583862
TI  - Simulation of wind turbine wakes using the actuator line technique.
AB  - The actuator line technique was introduced as a numerical tool to be employed in
      combination with large eddy simulations to enable the study of wakes and wake
      interaction in wind farms. The technique is today largely used for studying basic
      features of wakes as well as for making performance predictions of wind farms. In
      this paper, we give a short introduction to the wake problem and the actuator
      line methodology and present a study in which the technique is employed to
      determine the near-wake properties of wind turbines. The presented results
      include a comparison of experimental results of the wake characteristics of the
      flow around a three-bladed model wind turbine, the development of a simple
      analytical formula for determining the near-wake length behind a wind turbine and
      a detailed investigation of wake structures based on proper orthogonal
      decomposition analysis of numerically generated snapshots of the wake. 

PMID- 25583863
TI  - Application of damage detection methods using passive reconstruction of impulse
      response functions.
AB  - In structural health monitoring (SHM), using only the existing noise has long
      been an attractive goal. The advances in understanding cross-correlations in
      ambient noise in the past decade, as well as new understanding in damage
      indication and other advanced signal processing methods, have continued to drive
      new research into passive SHM systems. Because passive systems take advantage of
      the existing noise mechanisms in a structure, offshore wind turbines are a
      particularly attractive application due to the noise created from the various
      aerodynamic and wave loading conditions. Two damage detection methods using a
      passively reconstructed impulse response function, or Green's function, are
      presented. Damage detection is first studied using the reciprocity of the impulse
      response functions, where damage introduces new nonlinearities that break down
      the similarity in the causal and anticausal wave components. Damage detection and
      localization are then studied using a matched-field processing technique that
      aims to spatially locate sources that identify a change in the structure. Results
      from experiments conducted on an aluminium plate and wind turbine blade with
      simulated damage are also presented. 

PMID- 25583864
TI  - Aspects of structural health and condition monitoring of offshore wind turbines.
AB  - Wind power has expanded significantly over the past years, although reliability
      of wind turbine systems, especially of offshore wind turbines, has been many
      times unsatisfactory in the past. Wind turbine failures are equivalent to crucial
      financial losses. Therefore, creating and applying strategies that improve the
      reliability of their components is important for a successful implementation of
      such systems. Structural health monitoring (SHM) addresses these problems through
      the monitoring of parameters indicative of the state of the structure examined.
      Condition monitoring (CM), on the other hand, can be seen as a specialized area
      of the SHM community that aims at damage detection of, particularly, rotating
      machinery. The paper is divided into two parts: in the first part, advanced
      signal processing and machine learning methods are discussed for SHM and CM on
      wind turbine gearbox and blade damage detection examples. In the second part, an
      initial exploration of supervisor control and data acquisition systems data of an
      offshore wind farm is presented, and data-driven approaches are proposed for
      detecting abnormal behaviour of wind turbines. It is shown that the advanced
      signal processing methods discussed are effective and that it is important to
      adopt these SHM strategies in the wind energy sector. 

PMID- 25583865
TI  - Seismic analysis of offshore wind turbines on bottom-fixed support structures.
AB  - This study investigates the seismic response of a horizontal axis wind turbine on
      two bottom-fixed support structures for transitional water depths (30-60 m), a
      tripod and a jacket, both resting on pile foundations. Fully coupled, nonlinear
      time-domain simulations on full system models are carried out under combined wind
      wave-earthquake loadings, for different load cases, considering fixed and
      flexible foundation models. It is shown that earthquake loading may cause a
      significant increase of stress resultant demands, even for moderate peak ground
      accelerations, and that fully coupled nonlinear time-domain simulations on full
      system models are essential to capture relevant information on the moment demand
      in the rotor blades, which cannot be predicted by analyses on simplified models
      allowed by existing standards. A comparison with some typical design load cases
      substantiates the need for an accurate seismic assessment in sites at risk from
      earthquakes. 

PMID- 25583866
TI  - Dynamic response signatures of a scaled model platform for floating wind turbines
      in an ocean wave basin.
AB  - Understanding of dynamic behaviour of offshore wind floating substructures is
      extremely important in relation to design, operation, maintenance and management
      of floating wind farms. This paper presents assessment of nonlinear signatures of
      dynamic responses of a scaled tension-leg platform (TLP) in a wave tank exposed
      to different regular wave conditions and sea states characterized by the
      Bretschneider, the Pierson-Moskowitz and the JONSWAP spectra. Dynamic responses
      of the TLP were monitored at different locations using load cells, a camera-based
      motion recognition system and a laser Doppler vibrometer. The analysis of
      variability of the TLP responses and statistical quantification of their
      linearity or nonlinearity, as non-destructive means of structural monitoring from
      the output-only condition, remains a challenging problem. In this study, the
      delay vector variance (DVV) method is used to statistically study the degree of
      nonlinearity of measured response signals from a TLP. DVV is observed to create a
      marker estimating the degree to which a change in signal nonlinearity reflects
      real-time behaviour of the structure and also to establish the sensitivity of the
      instruments employed to these changes. The findings can be helpful in
      establishing monitoring strategies and control strategies for undesirable levels
      or types of dynamic response and can help to better estimate changes in system
      characteristics over the life cycle of the structure. 

PMID- 25583867
TI  - Emerging trends in vibration control of wind turbines: a focus on a dual control
      strategy.
AB  - The paper discusses some of the recent developments in vibration control
      strategies for wind turbines, and in this context proposes a new dual control
      strategy based on the combination and modification of two recently proposed
      control schemes. Emerging trends in the vibration control of both onshore and
      offshore wind turbines are presented. Passive, active and semi-active structural
      vibration control algorithms have been reviewed. Of the existing controllers, two
      control schemes, active pitch control and active tendon control, have been
      discussed in detail. The proposed new control scheme is a merger of active tendon
      control with passive pitch control, and is designed using a Pareto-optimal
      problem formulation. This combination of controllers is the cornerstone of a dual
      strategy with the feature of decoupling vibration control from optimal power
      control as one of its main advantages, in addition to reducing the burden on the
      pitch demand. This dual control strategy will bring in major benefits to the
      design of modern wind turbines and is expected to play a significant role in the
      advancement of offshore wind turbine technologies. 

PMID- 25583868
TI  - Optimization of monopiles for offshore wind turbines.
AB  - The offshore wind industry currently relies on subsidy schemes to be competitive
      with fossil-fuel-based energy sources. For the wind industry to survive, it is
      vital that costs are significantly reduced for future projects. This can be
      partly achieved by introducing new technologies and partly through optimization
      of existing technologies and design methods. One of the areas where costs can be
      reduced is in the support structure, where better designs, cheaper fabrication
      and quicker installation might all be possible. The prevailing support structure
      design is the monopile structure, where the simple design is well suited to mass
      fabrication, and the installation approach, based on conventional impact driving,
      is relatively low-risk and robust for most soil conditions. The range of
      application of the monopile for future wind farms can be extended by using more
      accurate engineering design methods, specifically tailored to offshore wind
      industry design. This paper describes how state-of-the-art optimization
      approaches are applied to the design of current wind farms and monopile support
      structures and identifies the main drivers where more accurate engineering
      methods could impact on a next generation of highly optimized monopiles. 

PMID- 25583870
TI  - Efficient preliminary floating offshore wind turbine design and testing
      methodologies and application to a concrete spar design.
AB  - The current key challenge in the floating offshore wind turbine industry and
      research is on designing economic floating systems that can compete with fixed
      bottom offshore turbines in terms of levelized cost of energy. The preliminary
      platform design, as well as early experimental design assessments, are critical
      elements in the overall design process. In this contribution, a brief review of
      current floating offshore wind turbine platform pre-design and scaled testing
      methodologies is provided, with a focus on their ability to accommodate the
      coupled dynamic behaviour of floating offshore wind systems. The exemplary design
      and testing methodology for a monolithic concrete spar platform as performed
      within the European KIC AFOSP project is presented. Results from the experimental
      tests compared to numerical simulations are presented and analysed and show very
      good agreement for relevant basic dynamic platform properties. Extreme and
      fatigue loads and cost analysis of the AFOSP system confirm the viability of the
      presented design process. In summary, the exemplary application of the reduced
      design and testing methodology for AFOSP confirms that it represents a viable
      procedure during pre-design of floating offshore wind turbine platforms. 

PMID- 25583871
TI  - Wind turbine blade shear web disbond detection using rotor blade operational
      sensing and data analysis.
AB  - A wind turbine blade's structural dynamic response is simulated and analysed with
      the goal of characterizing the presence and severity of a shear web disbond.
      Computer models of a 5 MW offshore utility-scale wind turbine were created to
      develop effective algorithms for detecting such damage. Through data analysis and
      with the use of blade measurements, a shear web disbond was quantified according
      to its length. An aerodynamic sensitivity study was conducted to ensure
      robustness of the detection algorithms. In all analyses, the blade's flap-wise
      acceleration and root-pitching moment were the clearest indicators of the
      presence and severity of a shear web disbond. A combination of blade and non
      blade measurements was formulated into a final algorithm for the detection and
      quantification of the disbond. The probability of detection was 100% for the
      optimized wind speed ranges in laminar, 30% horizontal shear and 60% horizontal
      shear conditions. 

PMID- 25583869
TI  - New perspectives in offshore wind energy.
AB  - The design of offshore wind turbines is one of the most fascinating challenges in
      renewable energy. Meeting the objective of increasing power production with
      reduced installation and maintenance costs requires a multi-disciplinary
      approach, bringing together expertise in different fields of engineering. The
      purpose of this theme issue is to offer a broad perspective on some crucial
      aspects of offshore wind turbines design, discussing the state of the art and
      presenting recent theoretical and experimental studies. 

PMID- 25583872
TI  - Simplified rotor load models and fatigue damage estimates for offshore wind
      turbines.
AB  - The aim of rotor load models is to characterize and generate the thrust loads
      acting on an offshore wind turbine. Ideally, the rotor simulation can be replaced
      by time series from a model with a few parameters and state variables only. Such
      models are used extensively in control system design and, as a potentially new
      application area, structural optimization of support structures. Different rotor
      load models are here evaluated for a jacket support structure in terms of fatigue
      lifetimes of relevant structural variables. All models were found to be lacking
      in accuracy, with differences of more than 20% in fatigue load estimates. The
      most accurate models were the use of an effective thrust coefficient determined
      from a regression analysis of dynamic thrust loads, and a novel stochastic model
      in state-space form. The stochastic model explicitly models the quasi-periodic
      components obtained from rotational sampling of turbulent fluctuations. Its state
      variables follow a mean-reverting Ornstein-Uhlenbeck process. Although promising,
      more work is needed on how to determine the parameters of the stochastic model
      and before accurate lifetime predictions can be obtained without comprehensive
      rotor simulations. 

PMID- 25583873
TI  - Interventional cardiology: successes and failures.

PMID- 25583874
TI  - The Global Scientific Activities of the European Society of Cardiology:an
      intercontinental success story.

PMID- 25583875
TI  - Moderate acute alcohol intoxication has minimal effect on surround suppression
      measured with a motion direction discrimination task.
AB  - A well-studied paradox of motion perception is that, in order to correctly judge
      direction in high-contrast stimuli, subjects need to observe motion for longer in
      large stimuli than in small stimuli. This effect is one of several perceptual
      effects known generally as "surround suppression." It is usually attributed to
      center-surround antagonism between neurons in visual cortex, believed to be
      mediated by GABA-ergic inhibition. Accordingly, several studies have reported
      that this index of surround suppression is reduced in groups known to have
      reduced GABA-ergic inhibition, including older people and people with
      schizophrenia and major depressive disorder. In this study, we examined the
      effect on this index of moderate amounts of ethanol alcohol. Among its many
      effects on the nervous system, alcohol potentiates GABA-ergic transmission. We
      therefore hypothesized that it should further impair the perception of motion in
      large stimuli, resulting in a stronger surround-suppression index. This
      prediction was not borne out. Alcohol consumption slightly worsened duration
      thresholds for both large and small stimuli, but their ratio did not change
      significantly. 

PMID- 25583876
TI  - Spatial summation across the central visual field: implications for visual field
      testing.
AB  - In the present study, we measured the extent of spatial summation in the
      detection of image contrast within the central 40 degrees  visual field. Contrast
      detection thresholds (in 28 observers) were measured for a spot of light of 10
      different sizes [area: 0.03-1.92( degrees )(2)] at different retinal meridians (0
      degrees , 45 degrees , 90 degrees , 135 degrees , 180 degrees , 225 degrees , 270
      degrees , and 315 degrees ) and eccentricities (0 degrees , 5 degrees , 10
      degrees , 15 degrees , and 20 degrees ). Contrast detection thresholds were
      significantly affected by the size of the stimulus with sensitivity improving
      with stimulus size consistent with Ricco's law. Summation curves were similar
      across different spatial meridians, but the extent of spatial summation increased
      with retinal eccentricity consistent with previous reports. The size of the
      stimulus was also shown to affect contrast detection thresholds in the periphery.
      In particular, contrast detection thresholds decreased more rapidly with
      increasing eccentricity for a smaller target than a larger one. This difference
      in performance is accounted for by the accompanying change in Ac with
      eccentricity. In Experiment 2, we show that spatial uncertainty affected contrast
      detection, particularly at eccentric locations greater than 5 degrees , such that
      cueing the location of the stimulus improved contrast thresholds. Spatial
      uncertainty improved overall performance but did not affect the estimates of the
      critical areas of summation. The results of the present study indicate that, due
      to spatial summation, detection performance is highly dependent on the size of
      the stimulus, its eccentric location, and spatial uncertainty. Future perimetric
      methodologies must consider these factors to improve detection sensitivity. 

PMID- 25583877
TI  - Quality Improvement Education for Health Professionals: A Systematic Review.
AB  - Effective quality improvement (QI) education should improve patient care, but
      many curriculum studies do not include clinical measures. The research team
      evaluated the prevalence of QI curricula with clinical measures and their
      association with several curricular features. MEDLINE, Embase, CINAHL, and ERIC
      were searched through December 31, 2013. Study selection and data extraction were
      completed by pairs of reviewers. Of 99 included studies, 11% were randomized, and
      53% evaluated clinically relevant measures; 85% were from the United States. The
      team found that 49% targeted 2 or more health professions, 80% required a QI
      project, and 65% included coaching. Studies involving interprofessional learners
      (odds ratio [OR] = 6.55; 95% confidence interval [CI] = 2.71-15.82), QI projects
      (OR = 13.60; 95% CI = 2.92-63.29), or coaching (OR = 4.38; 95% CI = 1.79-10.74)
      were more likely to report clinical measures. A little more than half of the
      published QI curricula studies included clinical measures; they were more likely
      to include interprofessional learners, QI projects, and coaching.

PMID- 25583878
TI  - FBN1 polymorphisms in patients with the dilatative pathology of the ascending
      thoracic aorta.
AB  - OBJECTIVES: To investigate polymorphisms of the fibrillin-1 (FBN1) gene (namely,
      rs2118181, rs1036477, rs10519177, rs755251 and rs4774517) in a case-control study
      for dilatative pathology of the ascending thoracic aorta (DPATA) from
      Lithuanians. METHODS: We studied 312 patients who had undergone aortic
      reconstructive surgery for DPATA. These patients were sub-divided according to
      the phenotypes of their DPATA into (i) ascending aortic aneurysm (n = 160), (ii)
      post-stenotic dilatation of the ascending aorta due to aortic valve stenosis (n =
      79) and (iii) Stanford A dissection (n = 73). The reference group (n = 472) was
      recruited from a random sample screened within epidemiological studies of the
      Lithuanian population. FBN1 polymorphisms were studied by real-time polymerase
      chain-reaction amplification. RESULTS: Patients within the aortic dissection sub
      group had significantly higher minor allele frequencies in all five FBN1 single
      nucleotide polymorphism (SNPs) studied versus reference group subjects (P <
      0.0001). Minor allele frequencies in SNPs rs2118181, rs1036477 were significantly
      higher in those with aortic aneurysm when compared with the reference group (P =
      0.007). Thus, minor alleles of FBN1 SNPs studied were significantly associated
      with aortic dissection with odds ratios (ORs) 2.59-2.13, P < 0.001, while SNPs
      rs2118181 and rs1036477 with an increased risk of ascending aortic aneurysm [OR
      1.67, confidence interval (CI) 95% 1.61-2.40]. The association of FBN1 genotypes
      with each phenotype of DPATA was assessed using logistic regression models
      adjusted for gender, age and hypertension. The additive model best fitted SNPs
      rs2118181 and rs1036477 in association with the ascending aortic aneurysm sub
      group (OR 1.70, CI 95% 1.17-2.46) or the Stanford A dissection sub-group (OR
      2.64, CI 95% 1.66-4.19). A recessive model fitted best the association between
      SNPs rs10519177, rs755251, rs4774517 and Stanford A dissection (OR 4.31, CI 95%
      2.06-9.01). There were no significant associations between all studied FBN1 SNPs
      and post-stenotic or bicuspid aortic dilatation. CONCLUSIONS: Our study provides
      evidence for the following: (i) FBN1 SNPs rs2118181, rs1036477, rs10519177,
      rs4774517, rs755251 may increase susceptibility to aortic dissections and (ii)
      FBN1 SNPs rs2118181, rs1036477 to the formation of aortic aneurysms. Thus, these
      SNPs might be considered as biomarkers for identifying patients at risk for
      ascending aortic aneurysm and aortic dissection.

PMID- 25583880
TI  - Zoledronic acid effective as rescue treatment for ankylosing spondylitis
      refractory to TNF inhibition.

PMID- 25583881
TI  - Antibiotic management of methicillin-resistant Staphylococcus aureus--associated
      acute pulmonary exacerbations in cystic fibrosis.
AB  - OBJECTIVE: To review the treatment of methicillin-resistant Staphylococcus aureus
      (MRSA)-associated acute pulmonary exacerbations (APEs) in cystic fibrosis (CF).
      DATA SOURCES: A search of PubMed, MEDLINE, Cochrane Library and
      Clinicaltrials.gov databases through November 2014 was conducted using the search
      terms Staphylococcus aureus, methicillin-resistant Staphylococcus aureus,
      pulmonary exacerbations, and cystic fibrosis. STUDY SELECTION AND DATA
      EXTRACTION: All English-language research articles, case reports, and case series
      were evaluated. A total of 185 articles were identified related to MRSA and CF;
      30 articles that studied treatments of MRSA APE in CF were included. DATA
      SYNTHESIS: The persistent presence of MRSA in the respiratory tract of patients
      with CF has been associated with higher morbidity and an increased risk of death.
      Limited clinical data exist supporting the efficacy of any specific antimicrobial
      currently available for the treatment of APE secondary to MRSA. CONCLUSIONS: Data
      extrapolated from other populations suggest that vancomycin and linezolid are
      appropriate first-line treatment options for the treatment of APE secondary to
      MRSA. Second-line options include doxycycline or minocycline and
      trimethoprim/sulfamethoxazole, each of which may be useful in patients coinfected
      with other respiratory pathogens, for which they may provide overlapping
      coverage. Ceftaroline and ceftobiprole are newer antibiotics that appear to have
      a potential role in the treatment of APE in CF, but the latter is not currently
      available to the US market. Although potentially useful, clindamycin is limited
      by high rates of resistance, telavancin is limited by its toxicity profile, and
      tigecycline is limited by a lack of demonstrated efficacy for infections that are
      similar to that seen in the CF population. Studies investigating the clinical
      utility of the above-cited antibiotics for APE in CF secondary to MRSA are
      desperately needed to broaden the treatment armamentarium for this medical
      condition.

PMID- 25583879
TI  - A selective orexin-1 receptor antagonist attenuates stress-induced hyperarousal
      without hypnotic effects.
AB  - Orexins (OXs) are peptides produced by perifornical (PeF) and lateral
      hypothalamic neurons that exert a prominent role in arousal-related processes,
      including stress. A critical role for the orexin-1 receptor (OX1R) in complex
      emotional behavior is emerging, such as overactivation of the OX1R pathway being
      associated with panic or anxiety states. Here we characterize a brain-penetrant,
      selective, and high-affinity OX1R antagonist, compound 56 [N-({3-[(3-ethoxy-6
      methylpyridin-2-yl)carbonyl]-3-azabicyclo[4.1.0]hept-4-yl}methyl)-5
      (trifluoromethyl)pyrimidin-2-amine]. Ex vivo receptor binding studies
      demonstrated that, after subcutaneous administration, compound 56 crossed the
      blood-brain barrier and occupied OX1Rs in the rat brain at lower doses than
      standard OX1R antagonists GSK-1059865 [5-bromo-N-({1-[(3-fluoro-2
      methoxyphenyl)carbonyl]-5-methylpiperidin-2-yl}methyl)pyridin-2-amine], SB-334867
      [1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea], and SB-408124
      [1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea].
      Although compound 56 did not alter spontaneous sleep in rats and in wild-type
      mice, its administration in orexin-2 receptor knockout mice selectively promoted
      rapid eye movement sleep, demonstrating target engagement and specific OX1R
      blockade. In a rat model of psychological stress induced by cage exchange, the
      OX1R antagonist prevented the prolongation of sleep onset without affecting sleep
      duration. In a rat model of panic vulnerability (involving disinhibition of the
      PeF OX region) to threatening internal state changes (i.e., intravenous sodium
      lactate infusion), compound 56 attenuated sodium lactate-induced panic-like
      behaviors and cardiovascular responses without altering baseline locomotor or
      autonomic activity. In conclusion, OX1R antagonism represents a novel therapeutic
      strategy for the treatment of various psychiatric disorders associated with
      stress or hyperarousal states. 

PMID- 25583882
TI  - Start well, live better-a manifesto for the public's health.

PMID- 25583883
TI  - Treatment of depression in primary care.

PMID- 25583884
TI  - Is a strategy focused on super-utilizers equal to the task of health care system
      transformation? Yes.

PMID- 25583885
TI  - Is a strategy focused on super-utilizers equal to the task of health care system
      transformation? No.

PMID- 25583886
TI  - An early look at rates of uninsured safety net clinic visits after the Affordable
      Care Act.
AB  - PURPOSE: The Affordable Care Act of 2010 supports marked expansions in Medicaid
      coverage in the United States. As of January 1, 2014, a total of 25 states and
      the District of Columbia expanded their Medicaid programs. We tested the
      hypothesis that rates of uninsured safety net clinic visits would significantly
      decrease in states that implemented Medicaid expansion, compared with states that
      did not. METHODS: We undertook a longitudinal observational study of coverage
      status for adult visits in community health centers, from 12 months before
      Medicaid expansion (January 1, 2013 to December 31, 2013) through 6 months after
      expansion (January 1, 2014 to June 30, 2014). We analyzed data from 156 clinics
      in the OCHIN practice-based research network, with a shared electronic health
      record, located in 9 states (5 expanded Medicaid coverage and 4 did not).
      RESULTS: Analyses were based on 333,655 nonpregnant adult patients and their
      1,276,298 in-person billed encounters. Overall, clinics in the expansion states
      had a 40% decrease in the rate of uninsured visits in the postexpansion period
      and a 36% increase in the rate of Medicaid-covered visits. In contrast, clinics
      in the nonexpansion states had a significant 16% decline in the rate of uninsured
      visits but no change in the rate of Medicaid-covered visits. CONCLUSIONS: There
      was a substantial decrease in uninsured community health center visits and a
      significant increase in Medicaid-covered visits in study clinics in states that
      expanded Medicaid in 2014, whereas study clinics in states opting out of the
      expansion continued to have a high rate of uninsured visits. These findings
      suggest that Affordable Care Act-related Medicaid expansions have successfully
      decreased the number of uninsured safety net patients in the United States.

PMID- 25583887
TI  - Sustaining "meaningful use" of health information technology in low-resource
      practices.
AB  - PURPOSE: The implementation of electronic health records (EHRs) has been
      extensively studied, but their maintenance once implemented has not. The Regional
      Extension Center (REC) program provides implementation assistance to priority
      practices-those with limited financial, technical, and organizational resources
      but the assistance is time limited. Our objective was to identify potential
      barriers to maintenance of meaningful use of EHRs in priority primary care
      practices using a qualitative observational study for federally qualified health
      centers (FQHCs) and priority practices in Michigan. METHODS: We conducted
      cognitive task analysis (CTA) interviews and direct observations of health
      information technology implementation in FQHCs. In addition, we conducted
      semistructured interviews with implementation specialists serving priority
      practices to detect emergent themes relevant to maintenance. RESULTS: Maintaining
      EHR technology will require ongoing expert technical support indefinitely beyond
      implementation to address upgrades and security needs. Maintaining meaningful use
      for quality improvement will require ongoing support for leadership and change
      management. Priority practices not associated with larger systems lack access to
      the necessary technical expertise, financial resources, and leverage with vendors
      to continue alone. Rural priority practices are particularly challenged, because
      expertise is often not available locally. CONCLUSIONS: Priority practices,
      especially in rural areas, are at high risk for falling on the wrong side of a
      "digital divide" as payers and regulators enact increasing expectations for EHR
      use and information management. For those without affiliation to maintain the
      necessary expert staff, ongoing support will be needed for those practices to
      remain viable.

PMID- 25583888
TI  - Geographic and specialty distribution of US physicians trained to treat opioid
      use disorder.
AB  - PURPOSE: The United States is experiencing an epidemic of opioid-related deaths
      driven by excessive prescribing of opioids, misuse of prescription drugs, and
      increased use of heroin. Buprenorphine-naloxone is an effective treatment for
      opioid use disorder and can be provided in office-based settings, but this
      treatment is unavailable to many patients who could benefit. We sought to
      describe the geographic distribution and specialties of physicians obtaining
      waivers from the Drug Enforcement Administration (DEA) to prescribe buprenorphine
      naloxone to treat opioid use disorder and to identify potential shortages of
      physicians. METHODS: We linked physicians authorized to prescribe buprenorphine
      on the July 2012 DEA Drug Addiction Treatment Act (DATA) Waived Physician List to
      the American Medical Association Physician Masterfile to determine their age,
      specialty, rural-urban status, and location. We then mapped the location of these
      physicians and determined their supply for all US counties. RESULTS: Sixteen
      percent of psychiatrists had received a DEA DATA waiver (41.6% of all physicians
      with waivers) but practiced primarily in urban areas. Only 3.0% of primary care
      physicians, the largest group of physicians in rural America, had received
      waivers. Most US counties therefore had no physicians who had obtained waivers to
      prescribe buprenorphine-naloxone, resulting in more than 30 million persons who
      were living in counties without access to buprenorphine treatment. CONCLUSIONS:
      In the United States opioid use and related unintentional lethal overdoses
      continue to rise, particularly in rural areas. Increasing access to office-based
      treatment of opioid use disorder--particularly in rural America--is a promising
      strategy to address rising rates of opioid use disorder and unintentional lethal
      overdoses.

PMID- 25583889
TI  - General practitioners recognizing alcohol dependence: a large cross-sectional
      study in 6 European countries.
AB  - PURPOSE: Although alcohol dependence causes marked mortality and disease burden
      in Europe, the treatment rate is low. Primary care could play a key role in
      reducing alcohol-attributable harm by screening, brief interventions, and
      initiating or referral to treatment. This study investigates identification of
      alcohol dependence in European primary care settings. METHODS: Assessments from
      13,003 general practitioners, and 9,098 interviews (8,476 joint number of
      interviewed patients with a physician's assessment) were collected in 6 European
      countries. Alcohol dependence, comorbidities, and health service utilization were
      assessed by the general practitioner and independently using the Composite
      International Diagnostic Interview (CIDI) and other structured interviews.
      Weighted regression analyses were used to compare the impact of influencing
      variables on both types of diagnoses. RESULTS: The rate of patients being
      identified as alcohol dependent by the CIDI or a general practitioner was about
      equally high, but there was not a lot of overlap between cases identified.
      Alcohol-dependent patients identified by a physician were older, had higher rates
      of physicial comorbidity (liver disease, hypertension), and were socially more
      marginalized, whereas average consumption of alcohol and mental comorbidity were
      equally high in both groups. CONCLUSION: General practitioners were able to
      identify alcohol dependence, but the cases they identified differed from cases
      identified using the CIDI. The role of the CIDI as the reference standard should
      be reexamined, as older alcohol-dependent patients with severe comorbidities
      seemed to be missed in this assessment.

PMID- 25583891
TI  - Clinical relevance of fixed ratio vs lower limit of normal of FEV1/FVC in COPD:
      patient-reported outcomes from the CanCOLD cohort.
AB  - PURPOSE: The way in which spirometry is interpreted can lead to misdiagnosis of
      chronic obstructive pulmonary disease (COPD) resulting in inappropriate
      treatment. We compared the clinical relevance of 2 criteria for defining a low
      ratio of forced expiratory volume in 1 second to forced vital capacity
      (FEV1/FVC): the fixed ratio and the lower limit of normal. METHODS: We analyzed
      data from the cross-sectional phase of the population-based Canadian Cohort of
      Obstructive Lung Disease (CanCOLD) study. We determined associations of the
      spirometric criteria for airflow limitation with patient-reported adverse
      outcomes, including respiratory symptoms, disability, health status,
      exacerbations, and cardiovascular disease. Sensitivity analyses were used to
      explore the impact of age and severity of airflow limitation on these
      associations. RESULTS: We analyzed data from 4,882 patients aged 40 years and
      older. The prevalence of airflow limitation was 17% by fixed ratio and 11% by
      lower limit of normal. Patients classified as having airflow limitation by fixed
      ratio only had generally small, nonsignificant increases in the odds of adverse
      outcomes. Patients having airflow limitation based on both fixed ratio and lower
      limit of normal had larger, significant increases in odds. But strongest
      associations were seen for patients who had airflow limitation by both fixed
      ratio and lower limit of normal and also had a low FEV1, defined as one less than
      80% of the predicted value. CONCLUSIONS: Our results suggest that use of the
      fixed ratio alone may lead to misdiagnosis of COPD. A diagnosis established by
      both a low FEV1/FVC (according to fixed ratio and/or lower limit of normal) and a
      low FEV1 is strongly associated with clinical outcomes. Guidelines should be
      reconsidered to require both spirometry abnormalities so as to reduce
      overdiagnosis of COPD.

PMID- 25583890
TI  - Functional trajectories in the year before hospice.
AB  - PURPOSE: We undertook a study to identify distinct functional trajectories in the
      year before hospice, to determine how patients with these trajectories differ
      according to demographic characteristics and hospice diagnosis, and to evaluate
      the association between these trajectories and subsequent outcomes. METHODS: From
      an ongoing cohort study of 754 community-living persons aged 70 years or older,
      we evaluated data on 213 persons who were subsequently enrolled in hospice from
      March 1998 to December 2011. Disability in 13 basic, instrumental, and mobility
      activities was assessed during monthly telephone interviews through June 2012.
      RESULTS: In the year before hospice, we identified 5 clinically distinct
      functional trajectories, representing worsening cumulative burden of disability:
      late decline (10.8%), accelerated (10.8%), moderate (21.1%), progressively severe
      (24.9%), and persistently severe (32.4%). Participants with a cancer diagnosis
      (34.7%) had the most favorable functional trajectories (ie, lowest burden of
      disability), whereas those with neurodegenerative disease (21.1%) had the worst.
      Median survival in hospice was only 14 days and did not differ significantly by
      functional trajectory. Compared with participants in the persistently severe
      trajectory, those in the moderate trajectory had the highest likelihood of
      surviving and being independent in at least 1 activity in the month after hospice
      admission (adjusted odds ratio = 5.5; 95% CI, 1.9-35.9). CONCLUSIONS: The course
      of disability in the year before hospice differs greatly among older persons but
      is particularly poor among those with neurodegenerative disease. Late admission
      to hospice (as shown by the short survival), coupled with high levels of severe
      disability before hospice, highlight potential unmet palliative care needs for
      many older persons at the end of life.

PMID- 25583892
TI  - Laryngeal measurements and diagnostic tools for diagnosis of chronic obstructive
      pulmonary disease.
AB  - PURPOSE: The purpose of this study was to evaluate sensitivity, specificity, and
      positive and negative likelihood ratios of laryngeal height, lung function, and
      diagnostic questionnaires for screening and diagnosis of chronic obstructive
      pulmonary disease (COPD). METHODS: We undertook a cross-sectional study of 233
      people aged between 40 and 75 years. Measured variables were age, sex, weight,
      height, body mass index, tobacco use, maximum laryngeal height, and spirometry,
      and we administered a COPD questionnaire and the Lung Function Questionnaire.
      RESULTS: For laryngeal height, we found a positive likelihood ratio of 5.21, and
      for the Lung Function Questionnaire, we found a negative likelihood ratio of
      0.10. Combining a maximum laryngeal height of <=4 cm with Lung Function
      Questionnaire findings of <=18 yielded a positive likelihood ratio of 29.06, and
      a negative likelihood ratio of 0.26. CONCLUSIONS: The intrinsic validity of the
      lung function questionnaire makes it useful for screening. Combining Lung
      Function Questionnaire results and laryngeal height can help confirm or dismiss
      COPD.

PMID- 25583893
TI  - Ultrasound imaging for tailored treatment of patients with acute shoulder pain.
AB  - PURPOSE: The objective of this study was to assess the frequencies of ultrasound
      findings in patients with acute rotator cuff disorders in family medicine.
      METHODS: In a prospective observational study, 129 patients aged 18 to 65 years
      with acute shoulder pain in whom the family physician suspected rotator cuff
      disease underwent ultrasound imaging. RESULTS: Rotator cuff disease was present
      in 81% of the patients, and 50% of them had multiple disorders. Calcific
      tendonitis was the most frequently diagnosed specific disorder. An age of 40
      years or older was most strongly related to rotator cuff disease. CONCLUSIONS:
      Ultrasound imaging enables family physicians to rationalize treatment in nearly
      all patients who are aged 40 years and older with acute shoulder pain.

PMID- 25583894
TI  - Effectiveness of psychological treatments for depressive disorders in primary
      care: systematic review and meta-analysis.
AB  - PURPOSE: We performed a systematic review of the currently available evidence on
      whether psychological treatments are effective for treating depressed primary
      care patients in comparison with usual care or placebo, taking the type of
      therapy and its delivery mode into account. METHODS: Randomized controlled trials
      comparing a psychological treatment with a usual care or a placebo control in
      adult, depressed, primary care patients were identified by searches in MEDLINE,
      Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO up
      to December 2013. At least 2 reviewers extracted information from included
      studies and assessed the risk of bias. Random effects meta-analyses were
      performed using posttreatment depression scores as outcome. RESULTS: A total of
      30 studies with 5,159 patients met the inclusion criteria. Compared with control,
      the effect (standardized mean difference) at completion of treatment was -0.30
      (95% CI, -0.48 to -0.13) for face-to-face cognitive behavioral therapy (CBT), 
      0.14 (-0.40 to 0.12) for face-to-face problem-solving therapy, -0.24 (-0.47 to 
      0.02) for face-to-face interpersonal psychotherapy, -0.28 (-0.44 to -0.12) for
      other face-to-face psychological interventions, -0.43 (-0.62 to -0.24) for remote
      therapist-led CBT, -0.56 (-1.57 to 0.45) for remote therapist-led problem-solving
      therapy, -0.40 (-0.69 to -0.11) for guided self-help CBT, and -0.27 (-0.44 to 
      0.10) for no or minimal contact CBT. CONCLUSIONS: There is evidence that
      psychological treatments are effective in depressed primary care patients. For
      CBT approaches, substantial evidence suggests that interventions that are less
      resource intensive might have effects similar to more intense treatments.

PMID- 25583895
TI  - Efficacy and acceptability of pharmacological treatments for depressive disorders
      in primary care: systematic review and network meta-analysis.
AB  - PURPOSE: The purpose of this study was to investigate whether antidepressants are
      more effective than placebo in the primary care setting, and whether there are
      differences between substance classes regarding efficacy and acceptability.
      METHODS: We conducted literature searches in MEDLINE, Embase, Cochrane Central
      Register of Controlled Trials (CENTRAL), and PsycINFO up to December 2013.
      Randomized trials in depressed adults treated by primary care physicians were
      included in the review. We performed both conventional pairwise meta-analysis and
      network meta-analysis combining direct and indirect evidence. Main outcome
      measures were response and study discontinuation due to adverse effects. RESULTS:
      A total of 66 studies with 15,161 patients met the inclusion criteria. In network
      meta-analysis, tricyclic and tetracyclic antidepressants (TCAs), selective
      serotonin reuptake inhibitors (SSRIs), a serotonin-noradrenaline reuptake
      inhibitor (SNRI; venlafaxine), a low-dose serotonin antagonist and reuptake
      inhibitor (SARI; trazodone) and hypericum extracts were found to be significantly
      superior to placebo, with estimated odds ratios between 1.69 and 2.03. There were
      no statistically significant differences between these drug classes. Reversible
      inhibitors of monoaminoxidase A (rMAO-As) and hypericum extracts were associated
      with significantly fewer dropouts because of adverse effects compared with TCAs,
      SSRIs, the SNRI, a noradrenaline reuptake inhibitor (NRI), and noradrenergic and
      specific serotonergic antidepressant agents (NaSSAs). CONCLUSIONS: Compared with
      other drugs, TCAs and SSRIs have the most solid evidence base for being effective
      in the primary care setting, but the effect size compared with placebo is
      relatively small. Further agents (hypericum, rMAO-As, SNRI, NRI, NaSSAs, SARI)
      showed some positive results, but limitations of the currently available evidence
      makes a clear recommendation on their place in clinical practice difficult.

PMID- 25583896
TI  - Clinical practice guideline executive summary: Labor after cesarean/planned
      vaginal birth after cesarean.

PMID- 25583897
TI  - It's time to shine the light on direct-to-consumer advertising.
AB  - Pharmaceutical marketing is undergoing a transition as the business, delivery,
      and consumption of health care have increasingly become part of a growing digital
      landscape. Changes in pharmaceutical promotion also coincide with federal
      "sunshine" regulations newly implemented under the Affordable Care Act that
      require disclosure of certain marketing and industry payments to physicians.
      Collectively, these trends could lead to fundamental shifts in physician-directed
      and direct-to-consumer advertising (DTCA) that have yet to be adequately
      identified or explored. In response, we advocate for greater DTCA transparency,
      especially in the emerging digital forms of DTCA, to complement forthcoming
      sunshine transparency data. This will allow more robust study and understanding
      of changes in overall pharmaceutical marketing trends and their impact on health
      care consumption and behavior. This can also lead to more targeted state and
      federal policy interventions leveraging existing federal transparency regulations
      to ensure appropriate marketing, sales, and consumption of pharmaceutical
      products.

PMID- 25583899
TI  - 'Health is primary' launches to much fanfare at AAFP assembly.

PMID- 25583898
TI  - International collaboration in innovating health systems.

PMID- 25583901
TI  - STFM prepares family medicine educators to lead.

PMID- 25583900
TI  - ABFM's self-assessment module (SAM) revision process.

PMID- 25583902
TI  - Interprofessional education: a webinar featuring case examples.

PMID- 25583903
TI  - Training implications of Family Medicine for America's Health: a preview.

PMID- 25583904
TI  - A simplified questionnaire for self-assessment of hirsutism in population-based
      studies.
AB  - OBJECTIVE: The measurement of excess body hair is not straightforward. As the
      modified Ferriman-Gallwey (mFG) score is unsuitable for self-assessment and
      requires specialist training, a short, self-administered questionnaire to
      identify hirsutism was constructed and validated for large-scale application,
      particularly targeting population-based studies. DESIGN: A validation study was
      conducted to assess a new hirsutism questionnaire. METHODS: A total of 90 women
      aged 35-72 years who were enrolled in the Brazilian Longitudinal Study of Adult
      Health (ELSA-Brasil) were evaluated. A self-administered instrument containing
      four questions was designed to evaluate five body areas: upper lip, chin, chest,
      lower abdomen, and thighs with respect to the current distribution of body hair
      and that before 35 years of age. A score of 0-4 was attributed to each region
      based on drawings provided in the instrument. Test-retest reliability was
      evaluated by reformulating the initial questions. An independent medical
      examination was conducted to apply the gold standard, the mFG score. RESULTS: The
      area under the receiver operating characteristic curve was 0.93 (95% CI: 0.87
      0.99). A cut-off score of 5 showed the best balance between sensitivity (85%) and
      specificity (90%), with 88.9% accuracy. Spearman's correlation between current
      and past body hair score was calculated at 0.82 (P=0.000), and showed a test
      retest reliability of 0.49, with a trend toward similar answers regarding changes
      in the quantity of body hair over time, irrespective of how the questions were
      asked (P=0.000). CONCLUSION: The accuracy and internal consistency of this self
      administered questionnaire for the identification of hirsutism were good.
      Therefore, this questionnaire represents a useful tool for self-assessment of
      hirsutism in population-based studies.

PMID- 25583905
TI  - GH deficiency after traumatic brain injury: improvement in quality of life with
      GH therapy: analysis of the KIMS database.
AB  - OBJECTIVE: Prevalence of GH deficiency (GHD) caused by traumatic brain injury
      (TBI) is highly variable. Short-term studies show improvement in quality of life
      (QoL) during GH replacement (GHR), but long-term data are lacking. The aim of
      this study was to analyse the clinical characteristics of post-traumatic
      hypopituitarism and the QoL effects of long-term GHR. DESIGN/METHODS: Pfizer
      International Metabolic Database patients with GHD caused by TBI and by non
      functioning pituitary adenoma (NFPA) were compared regarding: clinical
      characteristics at baseline and 1-year of GHR, and QoL response up to 8-years of
      GHR (QoL-AGHDA total scores and dimensions) in relationship with country-specific
      norms. RESULTS: TBI patients compared with NFPA patients were younger, diagnosed
      with GHD 2.4 years later after primary disease onset (P<0.0001), had a higher
      incidence of isolated GHD, higher GH peak, a more favourable metabolic profile
      and worse QoL, were shorter by 0.9 cm (1.8 cm when corrected for age and gender;
      P=0.004) and received higher GH dose (mean difference: 0.04 mg/day P=0.006). In
      TBI patients, 1-year improvement in QoL was greater than in NFPA (change in QoL
      AGHDA score 5.0 vs 3.5, respectively, P=0.04) and was sustained over 8 years. In
      TBI patients, socialisation normalised after 1 year of GHR, self-confidence and
      tenseness after 6 years and no normalisation of tiredness and memory was
      observed. CONCLUSION: Compared with NFPA, TBI patients presented biochemically
      with less severe hypopituitarism and worse QoL scores. GHR achieved clinically
      relevant, long-term benefit in QoL.

PMID- 25583906
TI  - TERT promoter mutations are associated with distant metastases in papillary
      thyroid carcinoma.
AB  - OBJECTIVE: Transcriptional activating mutations in the promoter of the telomerase
      reverse transcriptase (TERT) gene were reported at high frequency in aggressive
      poorly differentiated and anaplastic thyroid cancers. By contrast, the relevance
      of these mutations in the metastatic behavior of well-differentiated thyroid
      cancer is still to be defined. The aim of this work was to investigate the
      frequency of TERT promoter mutations in a remarkable cohort of well
      differentiated papillary thyroid carcinoma that developed distant metastases (DM
      PTCs) and to establish whether these mutations may be predictive of metastatic
      behavior. DESIGN: We analyzed the frequency of TERT promoter mutations in a group
      of 43 highly aggressive DM-PTCs. As controls, we analyzed these mutations in a
      group of 78 PTCs without distant metastases (control-PTCs). The possible
      correlation between TERT promoter mutations and BRAF V600E mutation was also
      investigated. METHODS: TERT promoter mutational status was evaluated by direct
      sequencing of the hotspot harboring the C228T and the C250T mutations. RESULTS:
      In the overall cohort of 121 PTCs analyzed, 17% of cases (21/121) carried a
      mutation in the TERT promoter. Noticeably, 33% of DM-PTCs were mutated in the
      TERT promoter while only 9% of the control-PTCs showed a mutation in this locus.
      We also observed a positive association between BRAF V600E and TERT C228T
      mutations in the cohort of DM-PTCs. CONCLUSIONS: These results indicate that TERT
      promoter mutations are associated with the development of distant metastases in
      PTCs and may help in predicting aggressive behavior in this type of tumor.

PMID- 25583907
TI  - Long-term survival after extended resection of primary atrial myxosarcoma.
AB  - The vast majority of adult primary cardiac tumours (75%) are benign. The
      differentiation between malignant and benign lesions based on imaging is often
      difficult. Furthermore, it is challenging to distinguish between a cardiac myxoma
      and a myxosarcoma histologically. We report the case of a 48-year-old female who
      underwent resection of myxoma. Fourteen months postoperatively, she developed
      dyspnoea and evidence of local recurrence was observed. An open biopsy was
      performed and compared with the initially resected specimen. A primary cardiac
      myxosarcoma was diagnosed. Extended resection of the tumour including a part of
      the left atrium and the left lung was performed. Follow-up at 4 years shows no
      radiological evidence of any further recurrence and the patient is satisfied with
      a good quality of life. Despite the infrequent nature and particularly in view of
      the poor prognosis of cardiac myxosarcoma with a median overall survival of ~12
      17 months, we were able to demonstrate in our case that, with an extensive
      medical and surgical therapy and an interdisciplinary approach, a long-term
      disease-free survival can be achieved. 

PMID- 25583908
TI  - Vocal cord palsy as a presenting feature of sternoclavicular joint septic
      arthritis.
AB  - Sternoclavicular joint septic arthritis (SSA) is rare and often difficult to
      manage condition. The sternoclavicular joint is an unusual site of septic
      arthritis in healthy persons, but may be commonly involved in intravenous drug
      users, primary or secondary immunosuppressive disorders, infections or the
      presence of infected central lines. After thorough literature search, no cases
      have yet been reported on SSA leading to vocal cord palsy. The following case
      describes a male patient who presented to hospital with left vocal cord palsy and
      symptoms consistent with aero-digestive tract malignancy. Radiological
      examination and subsequent response to treatment demonstrated the only causative
      pathology to be an ipsilateral septic sternoclavicular joint. 

PMID- 25583909
TI  - Research on medical practices and the ethics of disclosure.

PMID- 25583910
TI  - Adolescents' perceptions of light and intermittent smoking in the United States.
AB  - BACKGROUND: Light smoking, consuming a few cigarettes daily, and intermittent, or
      nondaily, smoking patterns are increasingly common but carry health risks
      comparable to heavier smoking patterns. Nearly all smokers begin smoking as
      adolescents, who are at risk for developing these smoking patterns. Previous
      research suggests that smokers underestimate the risks associated with smoking.
      The extent to which adolescents perceive light and intermittent smoking as
      harmful has not been previously assessed. METHODS: Data from 24,658 US
      adolescents sampled by the 2012 National Youth Tobacco Survey, a national, school
      based, cross-sectional survey, were examined. Cross-tabulations and multivariate
      ordered probit regression models were constructed to describe correlates of US
      adolescents' perception of light and intermittent smoking. RESULTS: Although most
      adolescents (88.0%; 95% confidence interval [CI], 87.2% to 88.8%) reported
      beliefs that a heavier smoking pattern is very harmful, only 64.3% (95% CI; 63.2%
      to 65.3%) and 33.3% (95% CI; 32.0% to 34.6%) reported that light and intermittent
      smoking, respectively, are very harmful. Conversely, nearly one-quarter of US
      adolescents believed intermittent smoking causes little or no harm. Males,
      younger adolescents, Hispanics, and non-Hispanic blacks were more likely than
      their peers to view light and intermittent smoking patterns as less harmful.
      Those who were already light or intermittent smokers, those who used other
      tobacco products, and those who had a family member who used tobacco were also
      less likely to view their smoking patterns as harmful. CONCLUSIONS:
      Misconceptions about the safety of light and intermittent smoking are widespread
      among US adolescents. Significant public health attention is needed to redress
      these misperceptions.

PMID- 25583911
TI  - Online problem-solving therapy after traumatic brain injury: a randomized
      controlled trial.
AB  - BACKGROUND: Pediatric traumatic brain injury (TBI) contributes to impairments in
      functioning in everyday settings. Evidence suggests that online family problem
      solving therapy (FPST) may be effective in reducing adolescent behavioral
      morbidity. This article examines the efficacy of Counselor-Assisted Problem
      Solving (CAPS), a form of online FPST in improving long-term functional outcomes
      of adolescents with TBI relative to Internet resources only. METHODS: Children,
      aged 12 to 17 years, who were hospitalized in the previous 7 months for TBI were
      enrolled in a multisite, assessor-blinded randomized controlled trial. Consented
      participants were randomly assigned to CAPS or an Internet resource comparison
      (IRC) condition. Outcomes were assessed at baseline and at follow-ups 6, 12, and
      18 months postbaseline. The Child and Functional Assessment Scale and the Iowa
      Family Interaction Rating Scale (IFIRS) served as primary outcomes of child and
      family functioning respectively. RESULTS: For the Child and Functional Assessment
      Scale total, we found a significant group * time interaction, with less impaired
      functioning for the CAPS group than for the IRC group at the final follow-up.
      Parent education moderated the efficacy of CAPS on overall rates of impairment
      and school/work functioning, with the advantage of CAPS over IRC evident at the
      final follow-up only for participants with less-educated parents. Neither group
      differences nor group * time interactions were found for the IFIRS. CONCLUSIONS:
      Relatively brief, online treatment shortly after injury may result in long-term
      improvements in child functioning, particularly among families of lower
      socioeconomic status. Clinical implementation of CAPS during the initial months
      postinjury should be considered.

PMID- 25583912
TI  - Changes in body mass index associated with head start participation.
AB  - OBJECTIVES: The goal of this study was to determine if Head Start participation
      is associated with healthy changes in BMI. METHODS: The sample included children
      participating in Head Start between 2005 and 2013 and children from 2 comparison
      groups drawn from a Michigan primary care health system: 5405 receiving Medicaid
      and 19,320 not receiving Medicaid. Change in BMI z score from the beginning to
      the end of each of 2 academic years and the intervening summer was compared
      between groups by using piecewise linear mixed models adjusted for age, gender,
      and race/ethnicity. RESULTS: The total sample included 43,748 children providing
      83,239 anthropometric measures. The Head Start sample was 64.9% white, 10.8%
      black, and 14.4% Hispanic; 16.8% of the children were obese and 16.6% were
      overweight at the initial observation. Children who entered Head Start as obese
      exhibited a greater decline in the BMI z score during the first academic year
      versus the comparison groups (beta = -0.70 [SE: 0.05] vs -0.07 [0.08] in the
      Medicaid group [P < .001] and -0.15 [SE: 0.05] in the Not Medicaid group [P <
      .001]); patterns were similar for overweight children. Head Start participants
      were less obese, less overweight, and less underweight at follow-up than children
      in the comparison groups. CONCLUSIONS: Preschool-aged children with an unhealthy
      weight status who participated in Head Start had a significantly healthier BMI by
      kindergarten entry age than comparison children in a primary care health system
      (both those receiving and those not receiving Medicaid).

PMID- 25583913
TI  - Identifying autism in a brief observation.
AB  - BACKGROUND: Pediatricians, neurologists, and geneticists are important sources
      for autism surveillance, screening, and referrals, but practical time constraints
      limit the clinical utility of behavioral observations. We analyzed behaviors
      under favorable conditions (ie, video of autism evaluations reviewed by experts)
      to determine what is optimally observable within 10-minute samples, asked for
      referral impressions, and compared these to formal screening and developmental
      testing results. METHODS: Participants (n = 42, aged 15 to 33 months) were
      typically developing controls and children who screened positive during universal
      autism screening within a large community pediatric practice. Diagnostic
      evaluations were performed after screening to determine group status (autism,
      language delay, or typical). Licensed psychologists with toddler and autism
      expertise, unaware of diagnostic status, analyzed two 10-minute video samples of
      participants' autism evaluations, measuring 5 behaviors: Responding, Initiating,
      Vocalizing, Play, and Response to Name. Raters were asked for autism referral
      impressions based solely on individual 10-minute observations. RESULTS: Children
      who had autism showed more typical behavior (89% of the time) than atypical
      behavior (11%) overall. Expert raters missed 39% of cases in the autism group as
      needing autism referrals based on brief but highly focused observations.
      Significant differences in cognitive and adaptive development existed among
      groups, with receptive language skills differentiating the 3 groups. CONCLUSIONS:
      Brief clinical observations may not provide enough information about atypical
      behaviors to reliably detect autism risk. High prevalence of typical behaviors in
      brief samples may distort clinical impressions of atypical behaviors. Formal
      screening tools and general developmental testing provide critical data for
      accurate referrals.

PMID- 25583914
TI  - Misdiagnosis and missed diagnoses in foster and adopted children with prenatal
      alcohol exposure.
AB  - OBJECTIVE: The purpose of this article is to assess the rate of misdiagnosis and
      missed diagnoses of fetal alcohol spectrum disorders (FASD) among a population of
      foster and adopted youth referred to a children's mental health center. METHODS:
      Data were collected from a sample of 547 children who underwent a comprehensive
      multidisciplinary diagnostic evaluation. Utilizing current diagnostic criteria,
      children were diagnosed, as appropriate, with fetal alcohol syndrome, partial
      fetal alcohol syndrome, alcohol-related neurodevelopmental disorder, or alcohol
      related birth defects. Changes in rates of alcohol exposure-related diagnoses and
      cooccurring mental health disorders pre- and postassessment were analyzed by
      using McNemar's test for dependent proportions. RESULTS: Among 156 children and
      adolescents who met criteria for a diagnosis within the fetal alcohol spectrum,
      125 had never been diagnosed as affected by prenatal alcohol exposure, a missed
      diagnosis rate of 80.1%. Of the 31 who had been recognized before referral as
      affected by prenatal alcohol exposure, 10 children's FASD diagnoses were changed
      within the spectrum, representing a misdiagnosis rate of 6.4%. The remaining 21
      (13.5%) children's diagnoses stayed the same. There also were significant changes
      in the rate of mental health diagnosis, and learning disorders, communication
      disorders, and intellectual disability, objective signs of neurocognitive damage,
      were not recognized in a significant number of children with FASD. CONCLUSIONS:
      Within this clinical sample, 86.5% of youth with FASD had never been previously
      diagnosed or had been misdiagnosed. These high rates of missed diagnoses and
      misdiagnosis have significant implications for intervention and therapeutic
      services.

PMID- 25583915
TI  - Family hardships and serum cotinine in children with asthma.
AB  - BACKGROUND AND OBJECTIVE: A better understanding of how poverty-related hardships
      affect child health could highlight remediable intervention targets. Tobacco
      smoke exposure may be 1 such consequence of family hardship. Our objective was to
      explore the relationship between family hardships and tobacco exposure, as
      measured by serum cotinine, a tobacco metabolite, among children hospitalized for
      asthma. METHODS: We prospectively enrolled a cohort of 774 children, aged 1 to 16
      years, admitted for asthma or bronchodilator-responsive wheezing. The primary
      outcome was detectable serum cotinine. We assessed family hardships, including 11
      financial and social variables, through a survey of the child's caregiver. We
      used logistic regression to evaluate associations between family hardship and
      detectable cotinine. RESULTS: We had complete study data for 675 children; 57%
      were African American, and 74% were enrolled in Medicaid. In total, 56% of
      children had detectable cotinine. More than 80% of families reported >= 1
      hardship, and 41% reported >= 4 hardships. Greater numbers of hardships were
      associated with greater odds of having detectable cotinine. Compared with
      children in families with no hardships, those in families with >= 4 hardships had
      3.7-fold (95% confidence interval, 2.0-7.0) greater odds of having detectable
      serum cotinine in adjusted analyses. Lower parental income and educational
      attainment were also independently associated with detectable serum cotinine.
      CONCLUSIONS: Family hardships are prevalent and associated with detectable serum
      cotinine level among children with asthma. Family hardships and tobacco smoke
      exposure may be possible targets for interventions to reduce health disparities.

PMID- 25583916
TI  - Cognitive-behavioral counseling for exclusive breastfeeding in rural pediatrics:
      a cluster RCT.
AB  - OBJECTIVE: To test the effectiveness of cognitive-behavioral counseling on the
      rate and duration of exclusive breastfeeding (EBF) during the first 6 months of
      an infant's life compared with routine counseling. METHODS: A single blind
      cluster-randomized controlled trial was undertaken in 40 Union Councils of a
      rural district in the northwest province of Pakistan between May 2009 and April
      2010. By simple unmatched randomization, 20 Union Councils were each allocated to
      intervention and control arms. Two hundred twenty-four third trimester pregnant
      women in the intervention and 228 third trimester pregnant women in the control
      arm were enrolled and followed-up biweekly until 6 months postpartum. Analyses
      were by intention to treat. Mothers in the intervention group received 7 sessions
      of cognitive-behavioral counseling from antenatal to 6 months postpartum, whereas
      the control group received an equal number of routine sessions. Proportion of
      mothers exclusively breastfeeding at 6 months postpartum and duration of EBF
      through these 6 months was assessed. RESULTS: At 6 months postpartum, 59.6% of
      mothers in the intervention arm and 28.6% in the control arm were exclusively
      breastfeeding. This translates into a 60% reduced risk of stopping exclusively
      breastfeeding during the first 6 months (adjusted hazard ratio, 0.40 [95%
      confidence interval: 0.27-0.60], P < .001). Mothers in the intervention group
      were half as likely to use prelacteal feeds with their infants (adjusted relative
      risk, 0.51 [95% confidence interval: 0.34-0.78]). CONCLUSIONS: Compared with
      routine counseling, cognitive-behavioral counseling significantly prolonged the
      duration of EBF, doubling the rates of EBF at 6 months postpartum.

PMID- 25583918
TI  - Variation in rotavirus vaccine coverage by provider location and subsequent
      disease burden.
AB  - BACKGROUND: Rotavirus vaccines were introduced in the United States in 2006. Full
      series coverage is lower than for other vaccines, and disease continues to occur.
      We examined variation in vaccine coverage among provider locations and correlated
      coverage with the detection of rotavirus in children who sought treatment of
      severe acute gastroenteritis (AGE). METHODS: Vaccine records of children enrolled
      in an AGE surveillance program were obtained and children were grouped by the
      location that administered each child's 2-month vaccines. Cases were children
      with laboratory-confirmed rotavirus AGE; controls were children with rotavirus
      negative AGE or acute respiratory infection. Location-level coverage was
      calculated using >= 1 dose rotavirus vaccine coverage among controls and
      classified as low (<40%), medium (>= 40% to <80%), or high (>= 80%). Rotavirus
      detection rates among patients with AGE were calculated by vaccine coverage
      category. RESULTS: Of controls, 80.4% (n = 1123 of 1396) received >= 1 dose of
      rotavirus vaccine from 68 locations. Four (5.9%) locations, including a NICU,
      were low coverage, 22 (32.3%) were medium coverage, and 42 (61.8%) were high
      coverage. In low-coverage locations, 31.4% of patients with AGE were rotavirus
      positive compared with 13.1% and 9.6% in medium- and high-coverage locations,
      respectively. Patients with AGE from low-coverage locations had 3.3 (95%
      confidence interval 2.4-4.4) times the detection rate of rotavirus than patients
      with AGE from high vaccine coverage locations. CONCLUSIONS: We observed the
      highest detection of rotavirus disease among locations with low rotavirus vaccine
      coverage, suggesting that ongoing disease transmission is related to failure to
      vaccinate. Educational efforts focusing on timely rotavirus vaccine
      administration to age-eligible infants are needed.

PMID- 25583917
TI  - Natural BMI reductions and overestimation of obesity trial effectiveness.

PMID- 25583919
TI  - Quality improvement initiative to increase influenza vaccination in pediatric
      cancer patients.
AB  - BACKGROUND: Pediatric patients with cancer face more severe complications of
      influenza than healthy children. Although Centers for Disease Control and
      Prevention guidelines recommend yearly vaccination in these patients, in our
      large academic center, <60% of oncology patients receiving chemotherapy were
      immunized at baseline. Our objective was to increase this rate through a
      multifaceted quality improvement initiative. METHODS: Eligible patients were >6
      months old, within 1 year of receiving chemotherapy, >100 days from stem cell
      transplant, and had >= 1 outpatient oncology visit between September 1, 2012, and
      March 31, 2013. Five interventions were instituted concomitantly: (1) family
      education: influenza/vaccine handouts were provided to families in clinic waiting
      rooms; (2) health informatics: daily lists of outpatients due for immunization
      were generated from the electronic medical record and sent automatically to
      triage staff and nurses; (3) outpatient clinic: patients due for vaccination were
      given colored wristbands during triage to alert providers; (4) inpatient: vaccine
      order was built into admission order set; and (5) provider education: staff
      education was provided at conferences on screening of patients, vaccine ordering,
      and documentation of refusals/contraindications. RESULTS: The complete influenza
      immunization rate increased by 20.1% to 64.5%, and the proportion of patients
      receiving >= 1 dose of vaccination increased by 22.9% to 77.7%. Similar changes
      were noted across all cancer types, with highest rates of immunization in
      leukemia/lymphoma patients (86.8%) and lowest in patients after stem cell
      transplant (66.7%). CONCLUSIONS: Technology, education, and multidisciplinary
      clinical process changes increased influenza vaccination rates. Ongoing efforts
      are targeting subgroups with lowest rates of immunization.

PMID- 25583920
TI  - Caustic ingestions mimicking anaphylaxis: case studies and literature review.
AB  - Anaphylaxis presents in children with rapid involvement of typically 2 or more
      organ systems including cutaneous, gastrointestinal, and respiratory. Caustic
      ingestions (CI) may also present with acute involvement of cutaneous,
      gastrointestinal, and respiratory systems. We present 2 cases of "missed
      diagnosis" that illustrate how CI presenting with respiratory symptoms can be
      mistaken for anaphylaxis owing to these similarities. Both of these patients had
      delay in appropriate care for CI as a result. These cases demonstrate the
      importance of considering CI in children who have gastrointestinal symptoms,
      respiratory distress, and oropharyngeal edema. 

PMID- 25583922
TI  - Early discharge of infants and risk of readmission for jaundice.
AB  - OBJECTIVES: To examine the association between early discharge from hospital
      after birth and readmission to hospital for jaundice among term infants, and
      among infants discharged early, to investigate the perinatal risk factors for
      readmission for jaundice. METHODS: Birth data for 781,074 term live-born infants
      born in New South Wales, Australia from 2001 to 2010 were linked to hospital
      admission data. Logistic regression models were used to investigate the
      association between postnatal length of stay (LOS), gestational age (GA), and
      readmission for jaundice in the first 14 days of life. Other significant
      perinatal risk factors associated with readmission for jaundice were examined for
      infants discharged in the first 2 days after birth. RESULTS: Eight per 1000 term
      infants were readmitted for jaundice. Infants born at 37 weeks' GA with an LOS at
      birth of 0 to 2 days were over 9 times (adjusted odds ratio [aOR] 9.43; 95% CI,
      8.34-10.67) and at 38 weeks' GA were 4 times (aOR 4.05; 95% CI, 3.62-4.54) more
      likely to be readmitted for jaundice compared with infants born at 39 weeks' GA
      with an LOS of 3 to 4 days. Other significant risk factors for readmission for
      jaundice for infants discharged 0 to 2 days after birth included vaginal birth,
      born to mothers from an Asian country, born to first-time mothers, or being
      breastfed at discharge. CONCLUSIONS: This study can inform guidelines or policy
      about identifying infants at risk for readmission for jaundice and ensure that
      appropriate post-discharge follow-up is received.

PMID- 25583921
TI  - Epidemiology of infant meningococcal disease in the United States, 2006-2012.
AB  - BACKGROUND: The incidence of meningococcal disease is currently at historic lows
      in the United States; however, incidence remains highest among infants aged <1
      year. With routine use of Haemophilus influenzae type b and pneumococcal vaccines
      in infants and children in the United States, Neisseria meningitidis remains an
      important cause of bacterial meningitis in young children. METHODS: Data were
      collected from active, population- and laboratory-based surveillance for N
      meningitidis conducted through Active Bacterial Core surveillance during 2006
      through 2012. Expanded data collection forms were completed for infant cases
      identified in the surveillance area during 2006 through 2010. RESULTS: An
      estimated 113 cases of culture-confirmed meningococcal disease occurred annually
      among infants aged <1 year in the United States from 2006 through 2012, for an
      overall incidence of 2.74 per 100,000 infants. Among these cases, an estimated 6
      deaths occurred. Serogroup B was responsible for 64%, serogroup C for 12%, and
      serogroup Y for 16% of infant cases. Based on the expanded data collection forms,
      a high proportion of infant cases (36/58, 62%) had a smoker in the household and
      the socioeconomic status of the census tracts where infant meningococcal cases
      resided was lower compared with the other Active Bacterial Core surveillance
      areas and the United States as a whole. CONCLUSIONS: The burden of meningococcal
      disease remains highest in young infants and serogroup B predominates. Vaccines
      that provide long-term protection early in life have the potential to reduce the
      burden of meningococcal disease, especially if they provide protection against
      serogroup B meningococcal disease.

PMID- 25583923
TI  - Does low stomatal conductance or photosynthetic capacity enhance growth at
      elevated CO2 in Arabidopsis?
AB  - The objective of this study was to determine if low stomatal conductance (g)
      increases growth, nitrate (NO3 (-)) assimilation, and nitrogen (N) utilization at
      elevated CO2 concentration. Four Arabidopsis (Arabidopsis thaliana) near isogenic
      lines (NILs) differing in g were grown at ambient and elevated CO2 concentration
      under low and high NO3 (-) supply as the sole source of N. Although g varied by
      32% among NILs at elevated CO2, leaf intercellular CO2 concentration varied by
      only 4% and genotype had no effect on shoot NO3 (-) concentration in any
      treatment. Low-g NILs showed the greatest CO2 growth increase under N limitation
      but had the lowest CO2 growth enhancement under N-sufficient conditions. NILs
      with the highest and lowest g had similar rates of shoot NO3 (-) assimilation
      following N deprivation at elevated CO2 concentration. After 5 d of N
      deprivation, the lowest g NIL had 27% lower maximum carboxylation rate and 23%
      lower photosynthetic electron transport compared with the highest g NIL. These
      results suggest that increased growth of low-g NILs under N limitation most
      likely resulted from more conservative N investment in photosynthetic
      biochemistry rather than from low g.

PMID- 25583924
TI  - Imaging of lipids in microalgae with coherent anti-stokes Raman scattering
      microscopy.
AB  - Microalgae have great prospects as a sustainable resource of lipids for
      refinement into nutraceuticals and biodiesel, which increases the need for
      detailed insights into their intracellular lipid synthesis/storage mechanisms. As
      an alternative strategy to solvent- and label-based lipid quantification
      techniques, we introduce time-gated coherent anti-Stokes Raman scattering (CARS)
      microscopy for monitoring lipid contents in living algae, despite strong
      autofluorescence from the chloroplasts, at approximately picogram and subcellular
      levels by probing inherent molecular vibrations. Intracellular lipid droplet
      synthesis was followed in Phaeodactylum tricornutum algae grown under (1)
      light/nutrient-replete (control [Ctrl]), (2) light-limited (LL), and (3) nitrogen
      starved (NS) conditions. Good correlation (r(2) = 0.924) was found between lipid
      volume data yielded by CARS microscopy and total fatty acid content obtained from
      gas chromatography-mass spectrometry analysis. In Ctrl and LL cells, micron-sized
      lipid droplets were found to increase in number throughout the growth phases,
      particularly in the stationary phase. During more excessive lipid accumulation,
      as observed in NS cells, promising commercial harvest as biofuels and nutritional
      lipids, several micron-sized droplets were present already initially during
      cultivation, which then fused into a single giant droplet toward stationary phase
      alongside with new droplets emerging. CARS microspectroscopy further indicated
      lower lipid fluidity in NS cells than in Ctrl and LL cells, potentially due to
      higher fatty acid saturation. This agreed with the fatty acid profiles gathered
      by gas chromatography-mass spectrometry. CARS microscopy could thus provide
      quantitative and semiqualitative data at the single-cell level along with
      important insights into lipid-accumulating mechanisms, here revealing two
      different modes for normal and excessive lipid accumulation. 

PMID- 25583927
TI  - Malnutrition: our time is now!

PMID- 25583928
TI  - JPEN Journal Club 9. Prognostic Indicators.

PMID- 25583926
TI  - Reexamination of chlorophyllase function implies its involvement in defense
      against chewing herbivores.
AB  - Chlorophyllase (CLH) is a common plant enzyme that catalyzes the hydrolysis of
      chlorophyll to form chlorophyllide, a more hydrophilic derivative. For more than
      a century, the biological role of CLH has been controversial, although this
      enzyme has been often considered to catalyze chlorophyll catabolism during stress
      induced chlorophyll breakdown. In this study, we found that the absence of CLH
      does not affect chlorophyll breakdown in intact leaf tissue in the absence or the
      presence of methyl-jasmonate, which is known to enhance stress-induced
      chlorophyll breakdown. Fractionation of cellular membranes shows that Arabidopsis
      (Arabidopsis thaliana) CLH is located in the endoplasmic reticulum and the
      tonoplast of intact plant cells. These results indicate that CLH is not involved
      in endogenous chlorophyll catabolism. Instead, we found that CLH promotes
      chlorophyllide formation upon disruption of leaf cells, or when it is
      artificially mistargeted to the chloroplast. These results indicate that CLH is
      responsible for chlorophyllide formation after the collapse of cells, which led
      us to hypothesize that chlorophyllide formation might be a process of defense
      against chewing herbivores. We found that Arabidopsis leaves with genetically
      enhanced CLH activity exhibit toxicity when fed to Spodoptera litura larvae, an
      insect herbivore. In addition, purified chlorophyllide partially suppresses the
      growth of the larvae. Taken together, these results support the presence of a
      unique binary defense system against insect herbivores involving chlorophyll and
      CLH. Potential mechanisms of chlorophyllide action for defense are discussed.

PMID- 25583925
TI  - COBRA-LIKE2, a member of the glycosylphosphatidylinositol-anchored COBRA-LIKE
      family, plays a role in cellulose deposition in arabidopsis seed coat mucilage
      secretory cells.
AB  - Differentiation of the maternally derived seed coat epidermal cells into mucilage
      secretory cells is a common adaptation in angiosperms. Recent studies identified
      cellulose as an important component of seed mucilage in various species.
      Cellulose is deposited as a set of rays that radiate from the seed upon mucilage
      extrusion, serving to anchor the pectic component of seed mucilage to the seed
      surface. Using transcriptome data encompassing the course of seed development, we
      identified COBRA-LIKE2 (COBL2), a member of the glycosylphosphatidylinositol
      anchored COBRA-LIKE gene family in Arabidopsis (Arabidopsis thaliana), as
      coexpressed with other genes involved in cellulose deposition in mucilage
      secretory cells. Disruption of the COBL2 gene results in substantial reduction in
      the rays of cellulose present in seed mucilage, along with an increased
      solubility of the pectic component of the mucilage. Light birefringence
      demonstrates a substantial decrease in crystalline cellulose deposition into the
      cellulosic rays of the cobl2 mutants. Moreover, crystalline cellulose deposition
      into the radial cell walls and the columella appears substantially compromised,
      as demonstrated by scanning electron microscopy and in situ quantification of
      light birefringence. Overall, the cobl2 mutants display about 40% reduction in
      whole-seed crystalline cellulose content compared with the wild type. These data
      establish that COBL2 plays a role in the deposition of crystalline cellulose into
      various secondary cell wall structures during seed coat epidermal cell
      differentiation.

PMID- 25583929
TI  - A comparison of pressure distributions between two types of sockets in a bulbous
      stump.
AB  - BACKGROUND: This article describes a total surface bearing prosthetic socket for
      a patient (25-year-old female) with a bulbous stump. CASE DESCRIPTION AND
      METHODS: The subject had unstable excessive soft tissue at the distal end of the
      residuum. After 2 years of prosthetic use, she experienced several problems,
      including pain in the residual limb and knee joint. Pressure distribution was
      evaluated during ambulation. We also designed a total surface bearing socket with
      Velcro as suspension system to distribute the load evenly on the residual limb,
      and to facilitate donning procedure. FINDINGS AND OUTCOMES: The main site of
      weight bearing in the old prosthesis (patellar tendon bearing) was anterior
      proximal region of the residual limb, especially the patellar tendon. The
      pressure was almost 10 times higher than the distal region during level walking.
      Pressures were distributed more evenly with the total surface bearing socket
      design, and the donning was much easier. CONCLUSION: Pressure distribution within
      the socket could be affected by socket design and suspension system. Using the
      total surface bearing socket and Velcro as suspension system might facilitate
      donning of prosthesis and reduce traction at the end of residual limb during the
      swing phase of gait. CLINICAL RELEVANCE: Proper socket design and suspension
      system based on the amputees' need can facilitate rehabilitation process and lead
      to the amputee's satisfaction. The pressure is distributed more uniformly over
      the residual limb by the total surface bearing socket compared to the patellar
      tendon bearing socket for lower limb amputees with unusual stump shape.

PMID- 25583930
TI  - Carcinogenesis: integrative Cancer Research has concluded its 35th year in the
      service of the scientific community.

PMID- 25583937
TI  - Impacted permanent incisors associated with compound odontoma.
AB  - Odontomas are the most common odontogenic tumours of the maxillary bones,
      characterised by a slow growth and benign behaviour. They are usually small,
      asymptomatic and diagnosed after routine radiographic examination. The aim of
      this study was to report a case of a compound odontoma in the anterior maxilla of
      a 7-year-old girl, which was causing the impaction of the maxillary right central
      and lateral incisors, as well as the prolonged retention of the corresponding
      primary teeth. We also aimed to review the literature about these tumours, since
      they are not part of the dentist's day-to-day clinical practice. The clinical and
      radiographic features, the diagnosis and treatment of the case were discussed in
      this work. 

PMID- 25583938
TI  - Use of proton pump inhibitors in the management of gastroesophageal varices: a
      systematic review.
AB  - OBJECTIVE: To review the efficacy and safety of proton pump inhibitors (PPIs) in
      gastroesophageal varices (GEVs). DATA SOURCES: MEDLINE (1946 to September 2014),
      EMBASE (1974 to September 2014), International Pharmaceutical Abstracts (1970 to
      September 2014), Cochrane Central Register of Controlled Trials (1991 to
      September 2014), Google, and Google Scholar were searched using the following
      terms: esophageal varices, gastroesophageal varices, variceal hemorrhage,
      variceal bleeding, banding ligation, endoscopic variceal ligation, sclerotherapy,
      proton pump inhibitor, PPI, omeprazole, pantoprazole, lansoprazole,
      dexlansoprazole, rabeprazole, and esomeprazole. STUDY SELECTION AND DATA
      EXTRACTION: Published and unpublished studies evaluating the clinical outcomes of
      PPI use for GEVs were included regardless of study design. Non-English and
      nonhuman studies were excluded. DATA SYNTHESIS: Of 1156 studies, 20 were included
      after assessment. There was wide methodological heterogeneity and moderately high
      risk of bias among studies. Level I evidence suggests that PPIs reduce esophageal
      ulcer size post-elective esophageal ligation; the clinical importance of such
      findings is not known given the self-limiting nature of esophageal ulcer.
      Available evidence does not support a role of PPIs for long-term prophylaxis of
      portal hypertension-related bleeding and high-dose infusion for acute management
      of GEV hemorrhage. Retrospective data demonstrate a potential increase in the
      incidence of spontaneous bacterial peritonitis in patients with cirrhosis
      receiving PPIs. CONCLUSIONS: The best available evidence supports the use of
      short-course (10 days) PPI post-endoscopic variceal ligation to reduce ulcer size
      if ulcer healing is a concern. Practices such as high-dose infusion and prolonged
      use should be discouraged until evidence of benefit becomes available.

PMID- 25583939
TI  - A survey of intravenous immune globulin (IVIG) dosing strategies.

PMID- 25583940
TI  - Recurrent transaminitis induced by oral contraceptives during HIV infection.

PMID- 25583941
TI  - Spontaneous renal parenchymal hematoma associated with clopidogrel in a patient
      with diabetic nephropathy.

PMID- 25583942
TI  - Response to comment "Evaluation of aspirin use for primary prevention in diabetic
      patients".

PMID- 25583943
TI  - The price of abundance: how a wealth of experiences impoverishes savoring.
AB  - We investigated the long-standing-yet previously untested-idea that an abundance
      of desirable life experiences may undermine people's ability to savor simpler
      pleasures. In Study 1, we found that the more countries individuals had visited,
      the less inclined they were to savor a future trip to a pleasant but ordinary
      destination. In Study 2, we conducted a field experiment at a popular tourist
      attraction, where we manipulated participants' perceptions of their own
      experiential backgrounds; when participants were led to feel well-traveled, they
      devoted significantly less time to their visit compared with individuals who were
      led to feel less worldly. We replicate these findings in Study 3 and found
      evidence that the observed effect could not be easily explained by other
      mechanisms. Being a world traveler-or just feeling like one-may undermine the
      proclivity to savor visits to enjoyable but unextraordinary destinations by
      endowing individuals with a sense of abundance. 

PMID- 25583944
TI  - Access to care for children with emotional/behavioral difficulties.
AB  - Emotional/behavioral difficulties (EBDs) are increasingly diagnosed in children,
      constituting some of the most common chronic childhood conditions. Left
      untreated, EBDs pose long-term individual and population-level consequences.
      There is a growing evidence of disparities in EBD prevalence by various
      demographic characteristics. This article builds on this research by examining
      disparities in access to medical care for children with EBD. From 2008 to 2011,
      using data from the US National Health Interview Survey (N = 31,631) on sample
      children aged 4-17, we investigate (1) whether having EBD affects access to care
      (modeled as delayed care due to cost and difficulty making an appointment) and
      (2) the role demographic characteristics, health insurance coverage, and
      frequency of service use play in access to care for children with EBD. Results
      indicate that children with EBD experience issues in accessing care at more than
      twice the rate of children without EBD, even though they are less likely to be
      uninsured than their counterparts without EBD. In multivariable models, children
      with EBD are still more likely to experience delayed care due to cost and
      difficulty making a timely appointment, even after adjusting for frequency of
      health service use, insurance coverage, and demographic characteristics.

PMID- 25583945
TI  - Your friends know how long you will live: a 75-year study of peer-rated
      personality traits.
AB  - Although self-rated personality traits predict mortality risk, no study has
      examined whether one's friends can perceive personality characteristics that
      predict one's mortality risk. Moreover, it is unclear whether observers' reports
      (compared with self-reports) provide better or unique information concerning the
      personal characteristics that result in longer and healthier lives. To test
      whether friends' reports of personality predict mortality risk, we used data from
      a 75-year longitudinal study (the Kelly/Connolly Longitudinal Study on
      Personality and Aging). In that study, 600 participants were observed beginning
      in 1935 through 1938, when they were in their mid-20s, and continuing through
      2013. Male participants seen by their friends as more conscientious and open
      lived longer, whereas friend-rated emotional stability and agreeableness were
      protective for women. Friends' ratings were better predictors of longevity than
      were self-reports of personality, in part because friends' ratings could be
      aggregated to provide a more reliable assessment. Our findings demonstrate the
      utility of observers' reports in the study of health and provide insights
      concerning the pathways by which personality traits influence health.

PMID- 25583946
TI  - Farm characteristics, allergy symptoms, and risk of non-hodgkin lymphoid
      neoplasms in the agricultural health study.
AB  - BACKGROUND: Because of unique exposures, studies among farmers may yield insights
      into the relationship between allergies and non-Hodgkin lymphoid (NHL) neoplasms.
      We evaluated farm characteristics, allergic symptoms and conditions, and risk of
      NHL including specific subtypes in the Agricultural Health Study, a prospective
      cohort of farmers and spouses from North Carolina and Iowa. METHODS: We
      identified 710 incident cases of NHL (including chronic lymphocytic leukemia and
      multiple myeloma) among 82,370 participants with baseline data on crop and animal
      exposures, including 454 cases among 52,850 participants with baseline data on
      recent allergy symptoms (rhinitis) and living on a farm during childhood. HR and
      95% confidence intervals (CI) were calculated using multivariable-adjusted
      proportional hazards models. RESULTS: We observed reduced risks of NHL among
      farmers and spouses with rhinitis at baseline (HR, 0.63; 95% CI, 0.51-0.79),
      related to growing soybeans (HR, 0.80; 95% CI, 0.67-0.96), and among farmers who
      handled stored grains or hay (HR, 0.66; 95% CI, 0.52-0.82). Growing up on a farm
      was associated with increased NHL risk (HR, 1.51; 95% CI, 1.15-1.98). Results did
      not differ significantly by NHL subtype. CONCLUSIONS: Both the reduced risk of
      NHL among those with allergy symptoms and specific farm exposures in adulthood,
      and the increased risk among those who grew up on a farm suggest that the host
      immune response to agricultural allergens may influence NHL development. IMPACT:
      This prospective study is, to our knowledge, the first to investigate the
      relationship between allergy symptoms and NHL risk in farmers; confirmation of
      these findings in other farming populations is warranted. Cancer Epidemiol
      Biomarkers Prev; 24(3); 587-94. (c)2015 AACR.

PMID- 25583947
TI  - Prognostic value of angiopoietin-2 for death risk stratification in patients with
      metastatic colorectal carcinoma.
AB  - BACKGROUND: Baseline prognostic biomarkers stratifying treatment strategies in
      first-line metastatic colorectal cancer (mCRC) are lacking. Angiopoietin-2 (Ang
      2) is proposed as a potential biomarker in several cancers. We therefore decided
      to establish the additional prognostic value of Ang-2 for overall survival (OS)
      in patients with first-line mCRC. METHODS: We enrolled 177 patients treated with
      a bevacizumab containing chemotherapy in two prospective phase II clinical
      trials. Patient plasma samples were collected at baseline. ELISAs were used to
      measure Ang-2. RESULTS: The multivariable Cox model identified increased lactate
      dehydrogenase [HR, 1.60; 95% confidence interval (CI), 1.04-2.45; P = 0.03] and
      Ang-2 log-transformation level (HR, 1.59; 95% CI, 1.14-2.21; P = 0.0065) as two
      significant independent OS prognostic factors. It exhibited good calibration (P =
      0.8) and discrimination (C-index: 0.64; 95% CI, 0.58-0.68). Ang-2 parameter
      inclusion in the GERCOR reference model significantly and strongly improved its
      discriminative ability because the C-statistic increased significantly from 0.61
      to 0.63 (bootstrap mean difference = 0.07; 95% CI, 0.069-0.077). Interestingly,
      the addition of Ang-2 binary information with a 5 ng/mL cutoff value to the
      GERCOR model allowed the reclassification of intermediate-risk profile patients
      (41%) into two subsets of low and high risks. CONCLUSIONS: Our study provides
      robust evidence in favor of baseline Ang-2 prognostic value for OS adding to the
      conventional factors. Its assessment appears to be useful for the improvement in
      risk stratification for patients with intermediate-risk profile. IMPACT: Ang-2
      ability to predict OS at diagnosis could be of interest in the selection of
      patients eligible for intermittent or sequential therapeutic strategies dedicated
      to the optimization of patients' quality of life and chemotherapy cost
      effectiveness. Cancer Epidemiol Biomarkers Prev; 24(3); 603-12. (c)2015 AACR.

PMID- 25583952
TI  - Launching our new EBM cover.

PMID- 25583948
TI  - Body mass index is associated with gene methylation in estrogen receptor-positive
      breast tumors.
AB  - BACKGROUND: Although obesity is associated with breast cancer incidence and
      prognosis, the underlying mechanisms are poorly understood. Identification of
      obesity-associated epigenetic changes in breast tissue may advance mechanistic
      understanding of breast cancer initiation and progression. The goal of this
      study, therefore, was to investigate associations between obesity and gene
      methylation in breast tumors. METHODS: Using the Illumina GoldenGate Cancer I
      Panel, we estimated the association between body mass index (BMI) and gene
      methylation in 345 breast tumor samples from phase I of the Carolina Breast
      Cancer Study, a population-based case-control study. Multivariable linear
      regression was used to identify sites that were differentially methylated by BMI.
      Stratification by tumor estrogen receptor (ER) status was also conducted.
      RESULTS: In the majority of the 935 probes analyzed (87%), the average beta value
      increased with obesity (BMI >= 30). Obesity was significantly associated with
      differential methylation (FDR q < 0.05) in just two gene loci in breast tumor
      tissue overall and in 21 loci among ER-positive tumors. Obesity was associated
      with methylation of genes that function in immune response, cell growth, and DNA
      repair. CONCLUSIONS: Obesity is associated with altered methylation overall, and
      with hypermethylation among ER-positive tumors in particular, suggesting that
      obesity may influence the methylation of genes with known relevance to cancer.
      Some of these differences in methylation by obese status may influence levels of
      gene expression within breast cells. IMPACT: If our results are validated,
      obesity-associated methylation sites could serve as targets for prevention and
      treatment research. Cancer Epidemiol Biomarkers Prev; 24(3); 580-6. (c)2015 AACR.

PMID- 25583949
TI  - Effect of occupational exposures on lung cancer susceptibility: a study of gene
      environment interaction analysis.
AB  - BACKGROUND: Occupational exposures are known risk factors for lung cancer. Role
      of genetically determined host factors in occupational exposure-related lung
      cancer is unclear. METHODS: We used genome-wide association (GWA) data from a
      case-control study conducted in 6 European countries from 1998 to 2002 to
      identify gene-occupation interactions and related pathways for lung cancer risk.
      GWA analysis was performed for each exposure using logistic regression and
      interaction term for genotypes, and exposure was included in this model. Both SNP
      based and gene-based interaction P values were calculated. Pathway analysis was
      performed using three complementary methods, and analyses were adjusted for
      multiple comparisons. We analyzed 312,605 SNPs and occupational exposure to 70
      agents from 1,802 lung cancer cases and 1,725 cancer-free controls. RESULTS: Mean
      age of study participants was 60.1 +/- 9.1 years and 75% were male. Largest
      number of significant associations (P <= 1 * 10(-5)) at SNP level was
      demonstrated for nickel, brick dust, concrete dust, and cement dust, and for
      brick dust and cement dust at the gene-level (P <= 1 * 10(-4)). Approximately 14
      occupational exposures showed significant gene-occupation interactions with
      pathways related to response to environmental information processing via signal
      transduction (P < 0.001 and FDR < 0.05). Other pathways that showed significant
      enrichment were related to immune processes and xenobiotic metabolism.
      CONCLUSION: Our findings suggest that pathways related to signal transduction,
      immune process, and xenobiotic metabolism may be involved in occupational
      exposure-related lung carcinogenesis. IMPACT: Our study exemplifies an
      integrative approach using pathway-based analysis to demonstrate the role of
      genetic variants in occupational exposure-related lung cancer susceptibility.
      Cancer Epidemiol Biomarkers Prev; 24(3); 570-9. (c)2015 AACR.

PMID- 25583953
TI  - Biology coming full circle: joining the whole and the parts.
AB  - The new cover of Experimental Biology and Medicine features the hermeneutic
      circle of biology, a concept we have adapted from the hermeneutic principle that
      one understands the whole only in terms of each part and the parts only in terms
      of the whole. Our hermeneutic circle summarizes the course of experimental
      biology through 2500 years of the achievements of reductionist research
      (understanding the parts), which culminates in our ability to rapidly sequence
      the genome. Rather than returning along the same path in a constructionist
      approach that simply builds upon this knowledge, but in reverse, an alternative
      is to close the circle with synthetic constructions that seek to integrate the
      full complexity of biological and physiological systems (understanding the
      whole), of which organs-on-chips are one example. This closing of the circle
      cannot be a comprehensively accurate representation of biology, but it can be a
      synthetic one that effectively defines particular biological subsystems. The
      illustration of the hermeneutic circle of biology is also intended to suggest
      both the multiple cycles that may be required to reach such a synthesis and the
      expansion of the circle in an outward spiral as knowledge increases. Our
      commentary explains the symbolism of the new cover in a philosophical and
      scientific discussion. 

PMID- 25583955
TI  - Histological analysis of the structural composition of ankle ligaments.
AB  - BACKGROUND: Various ankle ligaments have different structural composition. The
      aim of this study was to analyze the morphological structure of ankle ligaments
      to further understand their function in ankle stability. METHODS: One hundred
      forty ligaments from 10 fresh-frozen cadaver ankle joints were dissected: the
      calcaneofibular, anterior, and posterior talofibular ligaments; the inferior
      extensor retinaculum, the talocalcaneal oblique ligament, the canalis tarsi
      ligament; the deltoid ligament; and the anterior tibiofibular ligament.
      Hematoxylin-eosin and Elastica van Gieson stains were used for determination of
      tissue morphology. RESULTS: Three different morphological compositions were
      identified: dense, mixed, and interlaced compositions. Densely packed ligaments,
      characterized by parallel bundles of collagen, were primarily seen in the lateral
      region, the canalis tarsi, and the anterior tibiofibular ligaments. Ligaments
      with mixed tight and loose parallel bundles of collagenous connective tissue were
      mainly found in the inferior extensor retinaculum and talocalcaneal oblique
      ligament. Densely packed and fiber-rich interlacing collagen was primarily seen
      in the areas of ligament insertion into bone of the deltoid ligament.
      CONCLUSIONS: Ligaments of the lateral region, the canalis tarsi, and the anterior
      tibiofibular ligaments have tightly packed, parallel collagen bundles and thus
      can resist high tensile forces. The mixed tight and loose, parallel oriented
      collagenous connective tissue of the inferior extensor retinaculum and the
      talocalcaneal oblique ligament support the dynamic positioning of the foot on the
      ground. The interlacing collagen bundles seen at the insertion of the deltoid
      ligament suggest that these insertion areas are susceptible to tension in a
      multitude of directions. CLINICAL RELEVANCE: The morphology and mechanical
      properties of ankle ligaments may provide an understanding of their response to
      the loads to which they are subjected.

PMID- 25583954
TI  - Cigarette smoking increases complication rate in forefoot surgery.
AB  - BACKGROUND: Cigarette smoking is known to increase perioperative complication
      rates, but no study to date has examined its effect specifically in forefoot
      surgery. The purpose of this study was to determine whether cigarette smoking
      increased complications after forefoot surgery. METHODS: The records of 602
      patients who had forefoot surgery between 2008 and 2010, and for whom smoking
      status was known, were reviewed. Patients were categorized into 3 groups based on
      smoking status: active smoker, smoker in the past, or nonsmoker. Medical records
      were reviewed for occurrence of complications, including nonunion, delayed union,
      delayed wound healing, infection, and persistent pain. RESULTS: Active smokers
      were found to have a notably higher complication rate (36.4%) after forefoot
      surgery than patients who previously (16.5%) or never (8.5%) smoked. Patients who
      continued to smoke in the perioperative period had the highest percentage of
      delayed union (3.0%), infection (9.1%), delayed wound healing (10.6%), and
      persistent pain (15.2%). Active cigarette smokers were 4.3 times more likely to
      have a complication than nonsmokers. Patients who smoked at any point in the past
      but quit prior to surgery were 1.9 times more likely than nonsmokers to incur a
      complication. The average time of smoking cessation for patients who had smoked
      at any point in the past but had quit prior to surgery was 17 years. For active
      smokers, those with a complication smoked an average of 18 cigarettes daily,
      while those without a complication smoked 14 cigarettes daily. CONCLUSIONS:
      Before forefoot surgery, surgeons should educate patients who smoke about their
      increased risk of complications and encourage smoking cessation. LEVEL OF
      EVIDENCE: Level III, retrospective comparative study.

PMID- 25583957
TI  - The Meaning of Patient Experiences of Medically Unexplained Physical Symptoms.
AB  - Current diagnostic models in medical practice do not adequately account for
      patient symptoms that cannot be classified. At the moment, when all known
      diagnostic possibilities have been excluded, physicians-and patients-confront
      uncertainty in diagnosis, which gives rise to the label of Medically Unexplained
      Physical Symptoms (MUPS). This phenomenological study, conducted by two research
      teams in two geographic locations, sought to explore patients' experiences of
      prolonged uncertainty in diagnosis. Participants in this study described their
      experiences with and consequences of MUPS primarily in relation to levels of
      acuity and acceptance of uncertainty, the latter loosely correlated to length of
      time since onset of symptoms (the longer the time, the more forbearance
      participants expressed). We identified three experiential periods including the
      active search for a diagnosis, living with MUPS, and, finally,
      acceptance/resignation of their condition. Findings point to the heightened
      importance of the therapeutic relationship when dealing with uncertainty. 

PMID- 25583956
TI  - Improving Therapeutic Relationships: Joint Crisis Planning for Individuals With
      Psychotic Disorders.
AB  - Outcomes for individuals with psychosis remain far from acceptable. Recently,
      prominent psychiatrists have called for an improved understanding of the impact
      of social contexts, and how social contexts might influence the development and
      maintenance of mental health problems. A key social context for individuals with
      psychosis is the therapeutic relationship. As part of a trial of joint crisis
      planning in England, this qualitative study aimed to determine the mechanism
      through which joint crisis planning might affect the therapeutic relationship.
      Results suggest that routine processes in mental health care are affected by
      policy and organizational requirements for risk mitigation-aspects that undermine
      person-centered approaches. In contrast, strong therapeutic relationships are
      characterized by individualized care and reliable and respectful treatment. The
      Joint Crisis Plan intervention partially succeeded in reducing contextual
      influences on routine role enactments, facilitating the demonstration of respect
      and improving the therapeutic relationship. 

PMID- 25583959
TI  - Clinical Experiences With Clients Who Are Low-Income: Mental Health
      Practitioners' Perspectives.
AB  - The experiences of nine licensed mental health practitioners regarding their work
      with clients from low-income backgrounds were examined utilizing grounded theory
      methodology. Themes that emerged from the semi-structured interviews highlighted
      a rich narrative that portrayed the work as both deeply satisfying and inherently
      complex. Participants described the personal nature of this work, including
      countertransference elicited because of their own personal economic contexts and
      emotional reactions experienced within and outside the therapy room. Their
      stories acknowledged systematic challenges that act as barriers to treatment.
      Some participants noted that this has contributed to feelings of disillusionment
      toward the field as well as fears about the future of the mental health care.
      Based on these findings, we discuss implications for training, future research,
      and clinical practice. 

PMID- 25583958
TI  - Visibility and Voice: Aboriginal People Experience Culturally Safe and Unsafe
      Health Care.
AB  - In Canada, cultural safety (CS) is emerging as a theoretical and practice lens to
      orient health care services to meet the needs of Aboriginal people. Evidence
      suggests Aboriginal peoples' encounters with health care are commonly negative,
      and there is concern that these experiences can contribute to further adverse
      health outcomes. In this article, we report findings based on participatory
      action research drawing on Indigenous methods. Our project goal was to
      interrogate practices within one hospital to see whether and how CS for
      Aboriginal patients could be improved. Interviews with Aboriginal patients who
      had accessed hospital services were conducted, and responses were collated into
      narrative summaries. Using interlocking analysis, findings revealed a number of
      processes operating to produce adverse health outcomes. One significant outcome
      is the production of structural violence that reproduces experiences of
      institutional trauma. Positive culturally safe experiences, although less
      frequently reported, were described as interpersonal interactions with feelings
      visibility and therefore, treatment as a "human being." 

PMID- 25583960
TI  - "I'm No Superman": Understanding Diabetic Men, Masculinity, and Cardiac
      Rehabilitation.
AB  - Exercise-based cardiac rehabilitation (CR) programs help patients with coronary
      heart disease (CHD) reduce their risk of recurrent cardiac illness, disability,
      and death. However, men with CHD and Type 2 diabetes mellitus (T2DM) demonstrate
      lower attendance and completion of CR despite having a poor prognosis. Drawing on
      gender and masculinity theory, we report on a qualitative study of 16 Canadian
      diabetic men recently enrolled in CR. Major findings reflect two discursive
      positions men assumed to regain a sense of competency lost in illness: (a)
      working with the experts, or (b) rejection of biomedical knowledge. These
      positions underscore the varied and sometimes contradictory responses of
      seriously ill men to health guidance. Findings emphasize the priority given to
      the rehabilitation of a positive masculine identity. The analysis argues that
      gender, age, and employment status are powerful mechanisms of variable CR
      participation. 

PMID- 25583961
TI  - Nocardia cyriacigeorgica in an immunocompetent patient.

PMID- 25583969
TI  - Tackling the burden of cancer in the 21st century: understanding and
      communicating in new and future contexts.

PMID- 25583970
TI  - Development and Validation of a Stability-Indicating Liquid Chromatographic
      Method for Estimating Olmesartan Medoxomil Using Quality by Design.
AB  - The current studies entail systematic quality by design (QbD)-based development
      of a simple, rapid, sensitive and cost-effective stability-indicating method for
      the estimation of olmesartan medoxomil. Quality target method profile was defined
      and critical analytical attributes (CAAs) for the reverse-phase liquid
      chromatography method earmarked. Chromatographic separation accomplished on a C18
      column using acetonitrile and water (containing 0.1% orthophosphoric acid, pH
      3.5) in 40 : 60 (v/v) as mobile phase at a flow rate of 1.0 mL/min with UV
      detection at 243 nm. Risk assessment studies and screening studies facilitated
      comprehensive understanding of the factors affecting CAAs. The mobile phase ratio
      and flow rate were identified as critical method parameters (CMPs) and were
      systematically optimized using face-centered cubic design, evaluating for CAAs,
      namely peak area, retention time, theoretical plates and peak tailing.
      Statistical modelization was accomplished followed by response surface analysis
      for comprehending plausible interaction(s) among CMPs. Search for optimum
      solution was conducted through numerical and graphical optimization for
      demarcating the design space. Analytical method validation and subsequent forced
      degradation studies corroborated the method to be highly efficient for routine
      analysis of drug and its degradation products. The studies successfully
      demonstrate the utility of QbD approach for developing the highly sensitive
      liquid chromatographic method with enhanced method performance. 

PMID- 25583971
TI  - High-Throughput Determination of Octanol-Water Partition Coefficients by
      Ultrasound-Assisted Liquid-Phase Microextraction.
AB  - A method of high-throughput determination, which is based on ultrasound-assisted
      liquid-phase microextraction, was developed to measure directly the partition
      coefficients of n-octanol-water. In ultrasound-assisted liquid-phase
      microextraction, ultrasonic energy can facilitate the mass transfer process of
      six or more microextractors simultaneously. Therefore, high-throughput
      determination of n-octanol-water partition coefficients can be performed
      favorably, and the equilibrium time of each microextractor can be decreased
      effectively. Several experimental parameters including ultrasonic power and
      frequency, centrifugation conditions, extractant volume and sample concentration
      were analyzed and optimized at 25 degrees C. Under the optimum conditions, it
      only takes 2 min to reach extraction equilibrium, and the solutions of sample can
      be separated by centrifugation in 4 min. After centrifugation, the concentrations
      in n-octanol phases are analyzed with gas chromatography. The method was further
      evaluated with eight reference compounds and the findings demonstrated that this
      method is suitable to determine the partition coefficients of organic compounds
      accurately and quickly. Next, the method was exploited to measure the partition
      coefficients of n-octanol-water containing 20 organic compounds, which cover the
      [Formula: see text] values from 0.05 to 4.36, with comparatively low relative
      standard deviation (RSD) directly. The results of this study illustrated that the
      RSD (n = 6) was under 3%. 

PMID- 25583972
TI  - Analysis of Phenolic Compounds in Some Medicinal Herbs by LC-MS.
AB  - In this paper, a liquid chromatography-atmospheric pressure chemical ionization
      mass spectrometry in negative mode method was developed for the identification
      and quantitative determination of 13 individual phenolics (chlorogenic acid,
      caffeic acid, coumaric acid, ferulic acid, (+)-catechin, (-)-epicatechin, rutin,
      quercitrin, isoquercitrin, fisetin, isorhamnetin, hesperidin and chrysin) from
      ethanolic extracts [30, 50 and 70% (w/v)] of Calendula officinalis, Hypericum
      perforatum, Galium verum and Origanum vulgare and some commercial extracts of
      these medicinal herbs. Correlation coefficients (r(2)) from calibration curves
      for all the compounds were between 0.9971 and 0.9996. Limit of detection was in
      the range of 0.070-0.280 ug/mL and limit of quantification was from 0.233 to
      0.932 ug/mL. The method was partially validated and the results obtained are: the
      intra- and interday relative standard deviation values were within 0.086 and
      2.821% and recovery values vary from 95.84% (coumaric acid) to 103.20% (rutin). 

PMID- 25583973
TI  - Getting the most out of professional associations.
AB  - In this commentary, three public health professionals working in diverse career
      settings share their perspectives on how to get the most out of professional
      associations. This article demonstrates how you can benefit from active
      involvement in your membership in professional associations and attending
      professional conferences. Methods to participate actively in your association
      include volunteering for one-time opportunities or standing committees,
      mentoring, and reviewing publications and manuscripts. Being active in
      professional organizations, such as the Society for Public Health Education,
      offers personal career development skill-building and opportunities for
      leadership and mentoring across all career stages. Experiences on how
      participation in professional organizations helped shape the authors' careers are
      shared. 

PMID- 25583974
TI  - The formation of Streptococcus mutans persisters induced by the quorum-sensing
      peptide pheromone is affected by the LexA regulator.
AB  - The presence of multidrug-tolerant persister cells within microbial populations
      has been implicated in the resiliency of bacterial survival against antibiotic
      treatments and is a major contributing factor in chronic infections. The
      mechanisms by which these phenotypic variants are formed have been linked to
      stress response pathways in various bacterial species, but many of these
      mechanisms remain unclear. We have previously shown that in the cariogenic
      organism Streptococcus mutans, the quorum-sensing peptide CSP (competence
      stimulating peptide) pheromone was a stress-inducible alarmone that triggered an
      increased formation of multidrug-tolerant persisters. In this study, we
      characterized SMU.2027, a CSP-inducible gene encoding a LexA ortholog. We showed
      that in addition to exogenous CSP exposure, stressors, including heat shock,
      oxidative stress, and ofloxacin antibiotic, were capable of triggering expression
      of lexA in an autoregulatory manner akin to that of LexA-like transcriptional
      regulators. We demonstrated the role of LexA and its importance in regulating
      tolerance toward DNA damage in a noncanonical SOS mechanism. We showed its
      involvement and regulatory role in the formation of persisters induced by the CSP
      ComDE quorum-sensing regulatory system. We further identified key genes involved
      in sugar and amino acid metabolism, the clustered regularly interspaced short
      palindromic repeat (CRISPR) system, and autolysin from transcriptomic analyses
      that contribute to the formation of quorum-sensing-induced persister cells. 

PMID- 25583975
TI  - Small-molecule inhibitors of gram-negative lipoprotein trafficking discovered by
      phenotypic screening.
AB  - In Gram-negative bacteria, lipoproteins are transported to the outer membrane by
      the Lol system. In this process, lipoproteins are released from the inner
      membrane by the ABC transporter LolCDE and passed to LolA, a diffusible
      periplasmic molecular chaperone. Lipoproteins are then transferred to the outer
      membrane receptor protein, LolB, for insertion in the outer membrane. Here we
      describe the discovery and characterization of novel pyridineimidazole compounds
      that inhibit this process. Escherichia coli mutants resistant to the
      pyridineimidazoles show no cross-resistance to other classes of antibiotics and
      map to either the LolC or LolE protein of the LolCDE transporter complex. The
      pyridineimidazoles were shown to inhibit the LolA-dependent release of the
      lipoprotein Lpp from E. coli spheroplasts. These results combined with bacterial
      cytological profiling are consistent with LolCDE-mediated disruption of
      lipoprotein targeting to the outer membrane as the mode of action of these
      pyridineimidazoles. The pyridineimidazoles are the first reported inhibitors of
      the LolCDE complex, a target which has never been exploited for therapeutic
      intervention. These compounds open the door to further interrogation of the outer
      membrane lipoprotein transport pathway as a target for antimicrobial therapy. 

PMID- 25583976
TI  - Slow leakage of Ca-dipicolinic acid from individual bacillus spores during
      initiation of spore germination.
AB  - When exposed to nutrient or nonnutrient germinants, individual Bacillus spores
      can return to life through germination followed by outgrowth. Laser tweezers,
      Raman spectroscopy, and either differential interference contrast or phase
      contrast microscopy were used to analyze the slow dipicolinic acid (DPA) leakage
      (normally ~20% of spore DPA) from individual spores that takes place prior to the
      lag time, Tlag, when spores begin rapid release of remaining DPA. Major
      conclusions from this work with Bacillus subtilis spores were as follows: (i)
      slow DPA leakage from wild-type spores germinating with nutrients did not begin
      immediately after nutrient exposure but only at a later heterogeneous time T1;
      (ii) the period of slow DPA leakage (DeltaTleakage = Tlag - T1) was heterogeneous
      among individual spores, although the amount of DPA released in this period was
      relatively constant; (iii) increases in germination temperature significantly
      decreased T1 times but increased values of DeltaTleakage; (iv) upon germination
      with l-valine for 10 min followed by addition of d-alanine to block further
      germination, all germinated spores had T1 times of less than 10 min, suggesting
      that T1 is the time when spores become committed to germinate; (v) elevated
      levels of SpoVA proteins involved in DPA movement in spore germination decreased
      T1 and Tlag times but not the amount of DPA released in DeltaTleakage; (vi) lack
      of the cortex-lytic enzyme CwlJ increased DPA leakage during germination due to
      longer DeltaTleakage times in which more DPA was released; and (vii) there was
      slow DPA leakage early in germination of B. subtilis spores by the nonnutrients
      CaDPA and dodecylamine and in nutrient germination of Bacillus cereus and
      Bacillus megaterium spores. Overall, these findings have identified and
      characterized a new early event in Bacillus spore germination. 

PMID- 25583977
TI  - Mutations within the mepA operator affect binding of the MepR regulatory protein
      and its induction by MepA substrates in Staphylococcus aureus.
AB  - The expression of mepA, encoding the Staphylococcus aureus MepA multidrug efflux
      protein, is repressed by the MarR homologue MepR. Repression occurs through
      binding of two MepR dimers to an operator with two homologous and closely
      approximated pseudopalindromic binding sites (site 1 [S1] and site 2 [S2]). MepR
      binding is impeded in the presence of pentamidine, a MepA substrate. The effects
      of various mepA operator mutations on MepR binding were determined using
      electrophoretic mobility shift assays and isothermal titration calorimetry, and
      an in vivo confirmation of the effects observed was established for a fully
      palindromic operator mutant. Altering the S1-S2 spacing by 1 to 4 bp severely
      impaired S2 binding, likely due to a physical collision between adjacent MepR
      dimers. Extension of the spacing to 9 bp eliminated the S1 binding-mediated DNA
      allostery required for efficient S2 binding, consistent with positive cooperative
      binding of MepR dimers. Binding of a single dimer to S1 was maintained when S2
      was disrupted, whereas disruption of S1 eliminated any significant binding to S2,
      also consistent with positive cooperativity. Palindromization of binding sites,
      especially S2, enhanced MepR affinity for the mepA operator and reduced MepA
      substrate-mediated MepR induction. As a result, the on-off equilibrium between
      MepR and its binding sites was shifted toward the on state, resulting in less
      free MepR being available for interaction with inducing ligand. The selective
      pressure(s) under which mepA expression is advantageous likely contributed to the
      accumulation of mutations in the mepA operator, resulting in the current sequence
      from which MepR is readily induced by MepA substrates. 

PMID- 25583978
TI  - Hydrazidase, a novel amidase signature enzyme that hydrolyzes acylhydrazides.
AB  - The degradation mechanisms of natural and artificial hydrazides have been
      elucidated. Here we screened and isolated bacteria that utilize the acylhydrazide
      4-hydroxybenzoic acid 1-phenylethylidene hydrazide (HBPH) from soils.
      Physiological and phylogenetic studies identified one bacterium as Microbacterium
      sp. strain HM58-2, from which we purified intracellular hydrazidase, cloned its
      gene, and prepared recombinant hydrazidase using an Escherichia coli expression
      system. The Microbacterium sp. HM58-2 hydrazidase is a 631-amino-acid monomer
      that was 31% identical to indoleacetamide hydrolase isolated from Bradyrhizobium
      japonicum. Phylogenetic studies indicated that the Microbacterium sp. HM58-2
      hydrazidase constitutes a novel hydrazidase group among amidase signature
      proteins that are distributed within proteobacteria, actinobacteria, and
      firmicutes. The hydrazidase stoichiometrically hydrolyzed the acylhydrazide
      residue of HBPH to the corresponding acid and hydrazine derivative. Steady-state
      kinetics showed that the enzyme hydrolyzes structurally related 4
      hydrozybenzamide to hydroxybenzoic acid at a lower rate than HBPH, indicating
      that the hydrazidase prefers hydrazide to amide. The hydrazidase contains the
      catalytic Ser-Ser-Lys motif that is conserved among members of the amidase
      signature family; it shares a catalytic mechanism with amidases, according to
      mutagenesis findings, and another hydrazidase-specific mechanism must exist that
      compensates for the absence of the catalytic Ser residue. The finding that an
      environmental bacterium produces hydrazidase implies the existence of a novel
      bacterial mechanism of hydrazide degradation that impacts its ecological role. 

PMID- 25583980
TI  - The Importance of the Mentor-Mentee Relationship in Women's Desistance From
      Destructive Behaviors.
AB  - According to the literature on desistance, the process of reentering society
      after imprisonment is distinct from the process of desistance as the former is a
      broader, institutional process that may influence the latter. Scholars have also
      acknowledged gendered differences in both reentry and desistance processes. Among
      the array of players in the lives of formerly incarcerated individuals, mentors
      have become an increasingly popular form of social support in postincarceration
      programs--particularly for women in reentry. Given the increasing interest in
      mentoring programs, this study uses semistructured interviews with mentors (n=
      10) and clients (n= 11) in a women's postincarceration mentoring program to
      assess the role of mentors in the reentry process and the desistance process. It
      was found that mentors aid in these processes by serving as facilitators of
      change for women who are open to such change and by facilitating in constructive
      behavioral adjustments.

PMID- 25583979
TI  - The clinical role and cost-effectiveness of long-acting antiretroviral therapy.
AB  - BACKGROUND: Long-acting antiretroviral therapy (LA-ART) is currently under
      development and could improve outcomes for human immunodeficiency virus (HIV)
      infected individuals with poor daily ART adherence. METHODS: We used a computer
      simulation model to evaluate the cost-effectiveness of 3 LA-ART strategies vs
      daily oral ART for all: (1) LA-ART for patients with multiple ART failures; (2)
      second-line LA-ART for those failing first-line therapy; and (3) first-line LA
      ART for ART-naive patients. We calculated the maximum annual cost of LA-ART at
      which each strategy would be cost-effective at a willingness to pay of $100 000
      per quality-adjusted life-year. We assumed HIV RNA suppression on daily ART
      ranged from 0% to 91% depending on adherence, vs 91% suppression on LA-ART
      regardless of daily ART adherence. In sensitivity analyses, we varied adherence,
      efficacy of LA-ART and daily ART, and loss to follow-up. RESULTS: Relative to
      daily ART, LA-ART increased overall life expectancy by 0.15-0.24 years, and by
      0.51-0.89 years among poorly adherent patients, depending on the LA-ART strategy.
      LA-ART after multiple failures became cost-effective at an annual drug cost of
      $48 000; in sensitivity analysis, this threshold varied from $40 000-$70 000.
      Second-line LA-ART and first-line LA-ART became cost-effective at an annual drug
      cost of $26 000-$31 000 and $24 000-$27 000, vs $28 000 and $25 000 for current
      second-line and first-line regimens. CONCLUSIONS: LA-ART could improve survival
      of HIV patients, especially those with poor daily ART adherence. At an annual
      cost of $40 000-$70 000, LA-ART will offer good value for patients with multiple
      prior failures. To be a viable option for first- or second-line therapy, however,
      its cost must approach that of currently available regimens.

PMID- 25583981
TI  - The Treatment Perspectives of Mentally Ill Offenders in Medium- and High-Secure
      Forensic Settings in Flanders.
AB  - There is an increasing interest in mentally ill offenders' (MIOs) treatment
      experiences in forensic settings. This study focuses on the treatment
      perspectives of MIOs in treatment as well as in prison settings in Flanders.
      Seventeen MIOs were interviewed about the treatment they received. Data were
      analyzed using thematic analysis to derive key themes while acknowledging the
      individuality of the participants' experiences. Treatment perspectives of MIOs in
      both settings revolved around similar themes, including "good" staff and privacy.
      However, their views differed on two themes: MIOs in treatment settings reported
      on feelings of lacking control and experiencing too much pressure, whereas MIOs
      in prison settings reported the opposite. The positive experiences in prison
      settings may complicate the transition from prison to a forensic treatment
      setting. The study further underscores the major challenge to create more
      opportunities for MIOs to meet their needs of self-determination in secure
      forensic treatment settings. 

PMID- 25583982
TI  - Mechanism and ablation of arrhythmia following total cavopulmonary connection.
AB  - BACKGROUND: The ability to identify and ablate different arrhythmia mechanisms
      after the total cavopulmonary connection has not been studied in detail. METHODS
      AND RESULTS: After obtaining Institutional Review Board approval according to
      institutional guidelines, consecutive patients after a total cavopulmonary
      connection undergoing electrophysiology study over a 6-year period were included
      (2006-2012). Arrhythmia mechanism was determined, and the procedural outcome was
      defined as complete, partial success, or failure. A 12-point arrhythmia severity
      score was calculated for each patient at baseline and on follow-up. Fifty-seven
      procedures were performed on 52 patients (18.4 +/- 11.8 years; 53.0 +/- 27.2 kg).
      Access to the pulmonary venous atrium was necessary in 33 procedures, via
      fenestration (16) or transbaffle puncture (17), and in 2 cases, an additional
      retrograde approach was used. In total, 80 arrhythmias were identified in 47
      cases: macroreentrant (n = 25) or focal atrial tachycardia (n = 8),
      atrioventricular nodal reentry tachycardia (n = 13), reentry via an accessory
      pathway (n = 4) or via twin atrioventricular nodes (n = 4), ventricular
      tachycardia (n = 5), and undefined atrial tachycardia (n = 21). Procedural
      outcome in 32 patients who underwent ablation was complete success (n = 25),
      partial success (n = 3), failure (n = 3), or empirical ablation (n = 1). After
      successful ablation, there was a significant decrease in arrhythmia score over
      18.2 (4-32) months follow-up, with a sustained trend even in the face of
      arrhythmia recurrence (50%). CONCLUSIONS: Arrhythmia mechanism post total
      cavopulmonary connection is highly varied, encompassing simple and more complex
      substrates, documentation of which facilitates a strategic approach to invasive
      arrhythmia management. Despite the anatomic limitations, successful and
      clinically meaningful ablation is possible.

PMID- 25583984
TI  - Exuberant squamous metaplasia in an intraductal papilloma of breast.

PMID- 25583983
TI  - Scar dechanneling: new method for scar-related left ventricular tachycardia
      substrate ablation.
AB  - BACKGROUND: Ventricular tachycardia (VT) substrate ablation usually requires
      extensive ablation. Scar dechanneling technique may limit the extent of ablation
      needed. METHODS AND RESULTS: The study included 101 consecutive patients with
      left ventricular scar-related VT (75 ischemic patients; left ventricular ejection
      fraction, 36 +/- 13%). Procedural end point was the elimination of all identified
      conducting channels (CCs) by ablation at the CC entrance followed by abolition of
      residual inducible VTs. By itself, scar dechanneling rendered noninducibility in
      54.5% of patients; ablation of residual inducible VT increased noninducibility to
      78.2%. Patients needing only scar dechanneling had a shorter procedure (213 +/-
      64 versus 244 +/- 71 minutes; P = 0.027), fewer radiofrequency applications (19
      +/- 11% versus 27 +/- 18%; P = 0.01), and external cardioversion/defibrillation
      shocks (20% versus 65.2%; P < 0.001). At 2 years, patients needing scar
      dechanneling alone had better event-free survival (80% versus 62%) and lower
      mortality (5% versus 11%). Incomplete CC-electrogram elimination was the only
      independent predictor (hazard ratio, 2.54 [1.06-6.10]) for the primary end point.
      Higher end point-free survival rates were observed in patients noninducible after
      scar dechanneling (log-rank P = 0.013) and those with complete CC-electrogram
      elimination (log-rank P = 0.013). The complications rate was 6.9%, with no
      deaths. CONCLUSIONS: Scar dechanneling alone results in low recurrence and
      mortality rates in more than half of patients despite the limited ablation extent
      required. Residual inducible VT ablation improves acute results, but patients who
      require it have worse outcomes. Recurrences are mainly related to incomplete CC
      electrogram elimination.

PMID- 25583985
TI  - Long-Term Outcomes of ADHD: Academic Achievement and Performance.
AB  - OBJECTIVE: The aim of this study was to synthesize published data regarding long
      term effects of ADHD on information learned (measured via achievement tests) and
      success within the school environment (academic performance). METHOD: A
      systematic search identified 176 studies (1980-2012) of long-term (>=2 years)
      academic outcomes with ADHD. RESULTS: Achievement test outcomes (79%) and
      academic performance outcomes (75%) were worse in individuals with untreated ADHD
      compared with non-ADHD controls, also when IQ difference was controlled (72% and
      81%, respectively). Improvement in both outcome groups was associated with
      treatment, more often for achievement test scores (79%) than academic performance
      (42%), also when IQ was controlled (100% and 57%, respectively). More achievement
      test and academic performance outcomes improved with multimodal (100% and 67%,
      respectively) than pharmacological (75% and 33%) or non-pharmacological (75% and
      50%) treatment alone. CONCLUSION: ADHD adversely affects long-term academic
      outcomes. A greater proportion of achievement test outcomes improved with
      treatment compared with academic performance. Both improved most consistently
      with multimodal treatment.

PMID- 25583986
TI  - A novel antibody engineering strategy for making monovalent bispecific
      heterodimeric IgG antibodies by electrostatic steering mechanism.
AB  - Producing pure and well behaved bispecific antibodies (bsAbs) on a large scale
      for preclinical and clinical testing is a challenging task. Here, we describe a
      new strategy for making monovalent bispecific heterodimeric IgG antibodies in
      mammalian cells. We applied an electrostatic steering mechanism to engineer
      antibody light chain-heavy chain (LC-HC) interface residues in such a way that
      each LC strongly favors its cognate HC when two different HCs and two different
      LCs are co-expressed in the same cell to assemble a functional bispecific
      antibody. We produced heterodimeric IgGs from transiently and stably transfected
      mammalian cells. The engineered heterodimeric IgG molecules maintain the overall
      IgG structure with correct LC-HC pairings, bind to two different antigens with
      comparable affinity when compared with their parental antibodies, and retain the
      functionality of parental antibodies in biological assays. In addition, the
      bispecific heterodimeric IgG derived from anti-HER2 and anti-EGF receptor (EGFR)
      antibody was shown to induce a higher level of receptor internalization than the
      combination of two parental antibodies. Mouse xenograft BxPC-3, Panc-1, and Calu
      3 human tumor models showed that the heterodimeric IgGs strongly inhibited tumor
      growth. The described approach can be used to generate tools from two pre
      existent antibodies and explore the potential of bispecific antibodies. The
      asymmetrically engineered Fc variants for antibody-dependent cellular
      cytotoxicity enhancement could be embedded in monovalent bispecific heterodimeric
      IgG to make best-in-class therapeutic antibodies. 

PMID- 25583987
TI  - Substituting threonine 187 with alanine in p27Kip1 prevents pituitary
      tumorigenesis by two-hit loss of Rb1 and enhances humoral immunity in old age.
AB  - p27Kip1 (p27) is an inhibitor of cyclin-dependent kinases. Inhibiting p27 protein
      degradation is an actively developing cancer therapy strategy. One focus has been
      to identify small molecule inhibitors to block recruitment of Thr-187
      phosphorylated p27 (p27T187p) to SCF(Skp2/Cks1) ubiquitin ligase. Since
      phosphorylation of Thr-187 is required for this recruitment, p27T187A knockin
      (KI) mice were generated to determine the effects of systemically blocking
      interaction between p27 and Skp2/Cks1 on tumor susceptibility and other
      proliferation related mouse physiology. Rb1(+/-) mice develop pituitary tumors
      with full penetrance and the tumors are invariably Rb1(-/-), modeling
      tumorigenesis by two-hit loss of RB1 in humans. Immunization induced humoral
      immunity depends on rapid B cell proliferation and clonal selection in germinal
      centers (GCs) and declines with age in mice and humans. Here, we show that
      p27T187A KI prevented pituitary tumorigenesis in Rb1(+/-) mice and corrected
      decline in humoral immunity in older mice following immunization with sheep red
      blood cells (SRBC). These findings reveal physiological contexts that depend on
      p27 ubiquitination by SCF(Skp2-Cks1) ubiquitin ligase and therefore help forecast
      clinical potentials of Skp2/Cks1-p27T187p interaction inhibitors. We further show
      that GC B cells and T cells use different mechanisms to regulate their p27
      protein levels, and propose a T helper cell exhaustion model resembling that of
      stem cell exhaustion to understand decline in T cell-dependent humoral immunity
      in older age. 

PMID- 25583988
TI  - The association of receptor of activated protein kinase C 1(RACK1) with
      infectious bursal disease virus viral protein VP5 and voltage-dependent anion
      channel 2 (VDAC2) inhibits apoptosis and enhances viral replication.
AB  - Infectious bursal disease (IBD) is an acute, highly contagious, and
      immunosuppressive avian disease caused by IBD virus (IBDV). Our previous report
      indicates that IBDV VP5 induces apoptosis via interaction with voltage-dependent
      anion channel 2 (VDAC2). However, the underlying molecular mechanism is still
      unclear. We report here that receptor of activated protein kinase C 1 (RACK1)
      interacts with both VDAC2 and VP5 and that they could form a complex. We found
      that overexpression of RACK1 inhibited IBDV-induced apoptosis in DF-1 cells and
      that knockdown of RACK1 by small interfering RNA induced apoptosis associated
      with activation of caspases 9 and 3 and suppressed IBDV growth. These results
      indicate that RACK1 plays an antiapoptotic role during IBDV infection via
      interaction with VDAC2 and VP5, suggesting that VP5 sequesters RACK1 and VDAC2 in
      the apoptosis-inducing process. 

PMID- 25583989
TI  - A hypertrophic cardiomyopathy-associated MYBPC3 mutation common in populations of
      South Asian descent causes contractile dysfunction.
AB  - Hypertrophic cardiomyopathy (HCM) results from mutations in genes encoding
      sarcomeric proteins, most often MYBPC3, which encodes cardiac myosin binding
      protein-C (cMyBP-C). A recently discovered HCM-associated 25-base pair deletion
      in MYBPC3 is inherited in millions worldwide. Although this mutation causes
      changes in the C10 domain of cMyBP-C (cMyBP-C(C10mut)), which binds to the light
      meromyosin (LMM) region of the myosin heavy chain, the underlying molecular
      mechanism causing HCM is unknown. In this study, adenoviral expression of cMyBP
      C(C10mut) in cultured adult rat cardiomyocytes was used to investigate protein
      localization and evaluate contractile function and Ca(2+) transients, compared
      with wild-type cMyBP-C expression (cMyBP-C(WT)) and controls. Forty-eight hours
      after infection, 44% of cMyBP-C(WT) and 36% of cMyBP-C(C10mut) protein levels
      were determined in total lysates, confirming equal expression. Immunofluorescence
      experiments showed little or no localization of cMyBP-C(C10mut) to the C-zone,
      whereas cMyBP-C(WT) mostly showed C-zone staining, suggesting that cMyBP
      C(C10mut) could not properly integrate in the C-zone of the sarcomere.
      Subcellular fractionation confirmed that most cMyBP-C(C10mut) resided in the
      soluble fraction, with reduced presence in the myofilament fraction. Also, cMyBP
      C(C10mut) displayed significantly reduced fractional shortening, sarcomere
      shortening, and relaxation velocities, apparently caused by defects in sarcomere
      function, because Ca(2+) transients were unaffected. Co-sedimentation and protein
      cross-linking assays confirmed that C10(mut) causes the loss of C10 domain
      interaction with myosin LMM. Protein homology modeling studies showed significant
      structural perturbation in cMyBP-C(C10mut), providing a potential structural
      basis for the alteration in its mode of interaction with myosin LMM. Therefore,
      expression of cMyBP-C(C10mut) protein is sufficient to cause contractile
      dysfunction in vitro. 

PMID- 25583990
TI  - The histone methyltransferase Smyd2 is a negative regulator of macrophage
      activation by suppressing interleukin 6 (IL-6) and tumor necrosis factor alpha
      (TNF-alpha) production.
AB  - SET and MYND domain-containing 2 (Smyd2), a histone 3 lysine 4- and histone 3
      lysine 36 (H3K36)-specific methyltransferase, plays critical roles in cardiac
      development and tumorigenesis. However, the role of Smyd2 in immunity and
      inflammation remains poorly understood. In this study, we report that Smyd2 is a
      novel negative regulator for macrophage activation and M1 polarization. Elevated
      Smyd2 expression suppresses the production of proinflammatory cytokines,
      including IL-6 and TNF, and inhibits the expression of important cell surface
      molecules, including major MHC-II and costimulatory molecules. Furthermore,
      macrophages with high Smyd2 expression inhibit Th-17 cell differentiation but
      promote regulatory T cell differentiation as a result of increased TGF-beta
      production and decreased IL-6 secretion. In macrophages, Smyd2 specifically
      facilitates H3K36 dimethylation at Tnf and Il6 promoters to suppress their
      transcription and inhibits NF-kappaB and ERK signaling. Therefore, our data
      demonstrate that epigenetic modification by Smyd2-mediated H3K36 dimethylation at
      Tnf and Il6 promoters plays an important role in the regulation of macrophage
      activation during inflammation. 

PMID- 25583991
TI  - Selective homo- and heteromer interactions between the multiple organellar RNA
      editing factor (MORF) proteins in Arabidopsis thaliana.
AB  - RNA editing in plastids and mitochondria of flowering plants requires
      pentatricopeptide repeat proteins (PPR proteins) for site recognition and
      proteins of the multiple organellar RNA editing factor (MORF) family as
      cofactors. Two MORF proteins, MORF5 and MORF8, are dual-targeted to plastids and
      mitochondria; two are targeted to plastids, and five are targeted to
      mitochondria. Pulldown assays from Arabidopsis thaliana tissue culture extracts
      with the mitochondrial MORF1 and the plastid MORF2 proteins, respectively, both
      identify the dual-targeted MORF8 protein, showing that these complexes can
      assemble in the organelles. We have now determined the scope of potential
      interactions between the various MORF proteins by yeast two-hybrid, in vitro
      pulldown, and bimolecular fluorescence complementation assays. The resulting MORF
      MORF interactome identifies specific heteromeric MORF protein interactions in
      plastids and in mitochondria. Heteromers are observed for MORF protein
      combinations affecting a common site, suggesting their functional relevance. Most
      MORF proteins also undergo homomeric interactions. Submolecular analysis of the
      MORF1 protein reveals that the MORF-MORF protein connections require the C
      terminal region of the central conserved MORF box. This domain has no similarity
      to known protein modules and may form a novel surface for protein-protein
      interactions. 

PMID- 25583992
TI  - Cardiac transcriptome and dilated cardiomyopathy genes in zebrafish.
AB  - BACKGROUND: Genetic studies of cardiomyopathy and heart failure have limited
      throughput in mammalian models. Adult zebrafish have been recently pursued as a
      vertebrate model with higher throughput, but genetic conservation must be tested.
      METHODS AND RESULTS: We conducted transcriptome analysis of zebrafish heart and
      searched for fish homologues of 51 known human dilated cardiomyopathy-associated
      genes. We also identified genes with high cardiac expression and genes with
      differential expression between embryonic and adult stages. Among tested genes,
      30 had a single zebrafish orthologue, 14 had 2 homologues, and 5 had >=3
      homologues. By analyzing the expression data on the basis of cardiac abundance
      and enrichment hypotheses, we identified a single zebrafish gene for 14 of 19
      multiple-homologue genes and 2 zebrafish homologues of high priority for ACTC1.
      Of note, our data suggested vmhc and vmhcl as functional zebrafish orthologues
      for human genes MYH6 and MYH7, respectively, which are established molecular
      markers for cardiac remodeling. CONCLUSIONS: Most known genes for human dilated
      cardiomyopathy have a corresponding zebrafish orthologue, which supports the use
      of zebrafish as a conserved vertebrate model. Definition of the cardiac
      transcriptome and fetal gene program will facilitate systems biology studies of
      dilated cardiomyopathy in zebrafish.

PMID- 25583993
TI  - DNA methylation of lipid-related genes affects blood lipid levels.
AB  - BACKGROUND: Epigenetic mechanisms might be involved in the regulation of
      interindividual lipid level variability and thus may contribute to the
      cardiovascular risk profile. The aim of this study was to investigate the
      association between genome-wide DNA methylation and blood lipid levels high
      density lipoprotein cholesterol, low-density lipoprotein cholesterol,
      triglycerides, and total cholesterol. Observed DNA methylation changes were also
      further analyzed to examine their relationship with previous hospitalized
      myocardial infarction. METHODS AND RESULTS: Genome-wide DNA methylation patterns
      were determined in whole blood samples of 1776 subjects of the Cooperative Health
      Research in the Region of Augsburg F4 cohort using the Infinium
      HumanMethylation450 BeadChip (Illumina). Ten novel lipid-related CpG sites
      annotated to various genes including ABCG1, MIR33B/SREBF1, and TNIP1 were
      identified. CpG cg06500161, located in ABCG1, was associated in opposite
      directions with both high-density lipoprotein cholesterol (beta coefficient=
      0.049; P=8.26E-17) and triglyceride levels (beta=0.070; P=1.21E-27). Eight
      associations were confirmed by replication in the Cooperative Health Research in
      the Region of Augsburg F3 study (n=499) and in the Invecchiare in Chianti, Aging
      in the Chianti Area study (n=472). Associations between triglyceride levels and
      SREBF1 and ABCG1 were also found in adipose tissue of the Multiple Tissue Human
      Expression Resource cohort (n=634). Expression analysis revealed an association
      between ABCG1 methylation and lipid levels that might be partly mediated by ABCG1
      expression. DNA methylation of ABCG1 might also play a role in previous
      hospitalized myocardial infarction (odds ratio, 1.15; 95% confidence
      interval=1.06-1.25). CONCLUSIONS: Epigenetic modifications of the newly
      identified loci might regulate disturbed blood lipid levels and thus contribute
      to the development of complex lipid-related diseases.

PMID- 25583994
TI  - Pharmacogenomic determinants of the cardiovascular effects of dalcetrapib.
AB  - BACKGROUND: Dalcetrapib did not improve clinical outcomes, despite increasing
      high-density lipoprotein cholesterol by 30%. These results differ from other
      evidence supporting high-density lipoprotein as a therapeutic target. Responses
      to dalcetrapib may vary according to patients' genetic profile. METHODS AND
      RESULTS: We conducted a pharmacogenomic evaluation using a genome-wide approach
      in the dal-OUTCOMES study (discovery cohort, n=5749) and a targeted genotyping
      panel in the dal-PLAQUE-2 imaging trial (support cohort, n=386). The primary
      endpoint for the discovery cohort was a composite of cardiovascular events. The
      change from baseline in carotid intima-media thickness on ultrasonography at 6
      and 12 months was evaluated as supporting evidence. A single-nucleotide
      polymorphism was found to be associated with cardiovascular events in the
      dalcetrapib arm, identifying the ADCY9 gene on chromosome 16 (rs1967309;
      P=2.41*10(-8)), with 8 polymorphisms providing P<10(-6) in this gene. Considering
      patients with genotype AA at rs1967309, there was a 39% reduction in the
      composite cardiovascular endpoint with dalcetrapib compared with placebo (hazard
      ratio, 0.61; 95% confidence interval, 0.41-0.92). In patients with genotype GG,
      there was a 27% increase in events with dalcetrapib versus placebo. Ten single
      nucleotide polymorphism in the ADCY9 gene, the majority in linkage disequilibrium
      with rs1967309, were associated with the effect of dalcetrapib on intima-media
      thickness (P<0.05). Marker rs2238448 in ADCY9, in linkage disequilibrium with
      rs1967309 (r(2)=0.8), was associated with both the effects of dalcetrapib on
      intima-media thickness in dal-PLAQUE-2 (P=0.009) and events in dal-OUTCOMES
      (P=8.88*10(-8); hazard ratio, 0.67; 95% confidence interval, 0.58-0.78).
      CONCLUSIONS: The effects of dalcetrapib on atherosclerotic outcomes are
      determined by correlated polymorphisms in the ADCY9 gene. CLINICAL TRIAL
      INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00658515
      and NCT01059682.

PMID- 25583995
TI  - PLA2G10 Gene Variants, sPLA2 Activity, and Coronary Heart Disease Risk.
AB  - BACKGROUND: Observational studies report that secretory phospholipase A2 (sPLA2)
      activity is a marker for coronary heart disease (CHD) risk, and activity measures
      are thought to represent the composite activity of sPLA2-IIA, -V, and -X. The aim
      of this study was to use genetic variants of PLA2G10, encoding sPLA2-X, to
      investigate the contribution of sPLA2-X to the measure of sPLA2 activity and
      coronary heart disease (CHD) risk traits and outcome. METHODS AND RESULTS: Three
      PLA2G10 tagging single-nucleotide polymorphisms (rs72546339, rs72546340, and
      rs4003232) and a previously studied PLA2G10 coding single-nucleotide polymorphism
      rs4003228, R38C, were genotyped in a nested case: control cohort drawn from the
      prospective EPIC-Norfolk Study (2175 cases and 2175 controls). Meta-analysis of
      rs4003228 (R38C) and CHD was performed using data from the Northwick Park Heart
      Study II and 2 published cohorts AtheroGene and SIPLAC, providing in total an
      additional 1884 cases and 3119 controls. EPIC-Norfolk subjects in the highest
      tertile of sPLA2 activity were older and had higher inflammatory markers compared
      with those in the lowest tertile for sPLA2 activity. None of the PLA2G10 tagging
      single-nucleotide polymorphism nor R38C, a functional variant, were significantly
      associated with sPLA2 activity, intermediate CHD risk traits, or CHD risk. In
      meta-analysis, the summary odds ratio for R38C was odds ratio=0.97 (95%
      confidence interval, 0.77-1.22). CONCLUSIONS: PLA2G10 variants are not
      significantly associated with plasma sPLA2 activity or with CHD risk.

PMID- 25583997
TI  - Calreticulin inhibits commitment to adipocyte differentiation.

PMID- 25583996
TI  - The Erv41-Erv46 complex serves as a retrograde receptor to retrieve escaped ER
      proteins.
AB  - Signal-dependent sorting of proteins in the early secretory pathway is required
      for dynamic retention of endoplasmic reticulum (ER) and Golgi components. In this
      study, we identify the Erv41-Erv46 complex as a new retrograde receptor for
      retrieval of non-HDEL-bearing ER resident proteins. In cells lacking Erv41-Erv46
      function, the ER enzyme glucosidase I (Gls1) was mislocalized and degraded in the
      vacuole. Biochemical experiments demonstrated that the luminal domain of Gls1
      bound to the Erv41-Erv46 complex in a pH-dependent manner. Moreover, in vivo
      disturbance of the pH gradient across membranes by bafilomycin A1 treatment
      caused Gls1 mislocalization. Whole cell proteomic analyses of deletion strains
      using stable isotope labeling by amino acids in culture identified other ER
      resident proteins that depended on the Erv41-Erv46 complex for efficient
      localization. Our results support a model in which pH-dependent receptor binding
      of specific cargo by the Erv41-Erv46 complex in Golgi compartments identifies
      escaped ER resident proteins for retrieval to the ER in coat protein complex I
      formed transport carriers. 

PMID- 25584000
TI  - Minimize toxicity or preserve efficacy? A delicate trade-off in the management of
      older patients with lung cancer.

PMID- 25583998
TI  - Tubulin transport by IFT is upregulated during ciliary growth by a cilium
      autonomous mechanism.
AB  - The assembly of the axoneme, the structural scaffold of cilia and flagella,
      requires translocation of a vast quantity of tubulin into the growing cilium, but
      the mechanisms that regulate the targeting, quantity, and timing of tubulin
      transport are largely unknown. In Chlamydomonas, GFP-tagged alpha-tubulin enters
      cilia as an intraflagellar transport (IFT) cargo and by diffusion. IFT-based
      transport of GFP-tubulin is elevated in growing cilia and IFT trains carry more
      tubulin. Cells possessing both nongrowing and growing cilia selectively target
      GFP-tubulin into the latter. The preferential delivery of tubulin boosts the
      concentration of soluble tubulin in the matrix of growing versus steady-state
      cilia. Cilia length mutants show abnormal kinetics of tubulin transport. We
      propose that cells regulate the extent of occupancy of IFT trains by tubulin
      cargoes. During ciliary growth, IFT concentrates soluble tubulin in cilia and
      thereby promotes elongation of the axonemal microtubules. 

PMID- 25583999
TI  - A flipped ion pair at the dynein-microtubule interface is critical for dynein
      motility and ATPase activation.
AB  - Dynein is a motor protein that moves on microtubules (MTs) using the energy of
      adenosine triphosphate (ATP) hydrolysis. To understand its motility mechanism, it
      is crucial to know how the signal of MT binding is transmitted to the ATPase
      domain to enhance ATP hydrolysis. However, the molecular basis of signal
      transmission at the dynein-MT interface remains unclear. Scanning mutagenesis of
      tubulin identified two residues in alpha-tubulin, R403 and E416, that are
      critical for ATPase activation and directional movement of dynein. Electron
      cryomicroscopy and biochemical analyses revealed that these residues form salt
      bridges with the residues in the dynein MT-binding domain (MTBD) that work in
      concert to induce registry change in the stalk coiled coil and activate the
      ATPase. The R403-E3390 salt bridge functions as a switch for this mechanism
      because of its reversed charge relative to other residues at the interface. This
      study unveils the structural basis for coupling between MT binding and ATPase
      activation and implicates the MTBD in the control of directional movement. 

PMID- 25584001
TI  - Erlotinib versus docetaxel as second- or third-line therapy in patients with
      advanced non-small-cell lung cancer in the era of personalized medicine.

PMID- 25584003
TI  - Alternative strategy to achieve increased overall survival and better quality of
      life in patients with second-line advanced non-small-cell lung cancer.

PMID- 25584002
TI  - Safety and survival with GVAX pancreas prime and Listeria Monocytogenes
      expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer.
AB  - PURPOSE: GVAX pancreas, granulocyte-macrophage colony-stimulating factor
      secreting allogeneic pancreatic tumor cells, induces T-cell immunity to cancer
      antigens, including mesothelin. GVAX is administered with low-dose
      cyclophosphamide (Cy) to inhibit regulatory T cells. CRS-207, live-attenuated
      Listeria monocytogenes-expressing mesothelin, induces innate and adaptive
      immunity. On the basis of preclinical synergy, we tested prime/boost vaccination
      with GVAX and CRS-207 in pancreatic adenocarcinoma. PATIENTS AND METHODS:
      Previously treated patients with metastatic pancreatic adenocarcinoma were
      randomly assigned at a ratio of 2:1 to two doses of Cy/GVAX followed by four
      doses of CRS-207 (arm A) or six doses of Cy/GVAX (arm B) every 3 weeks. Stable
      patients were offered additional courses. The primary end point was overall
      survival (OS) between arms. Secondary end points were safety and clinical
      response. RESULTS: A total of 90 patients were treated (arm A, n = 61; arm B, n =
      29); 97% had received prior chemotherapy; 51% had received >= two regimens for
      metastatic disease. Mean number of doses (+/- standard deviation) administered in
      arms A and B were 5.5 +/- 4.5 and 3.7 +/- 2.2, respectively. The most frequent
      grade 3 to 4 related toxicities were transient fevers, lymphopenia, elevated
      liver enzymes, and fatigue. OS was 6.1 months in arm A versus 3.9 months in arm B
      (hazard ratio [HR], 0.59; P = .02). In a prespecified per-protocol analysis of
      patients who received at least three doses (two doses of Cy/GVAX plus one of CRS
      207 or three of Cy/GVAX), OS was 9.7 versus 4.6 months (arm A v B; HR, 0.53; P =
      .02). Enhanced mesothelin-specific CD8 T-cell responses were associated with
      longer OS, regardless of treatment arm. CONCLUSION: Heterologous prime/boost with
      Cy/GVAX and CRS-207 extended survival for patients with pancreatic cancer, with
      minimal toxicity.

PMID- 25584004
TI  - Randomized phase III trial comparing weekly docetaxel plus cisplatin versus
      docetaxel monotherapy every 3 weeks in elderly patients with advanced non-small
      cell lung cancer: the intergroup trial JCOG0803/WJOG4307L.
AB  - PURPOSE: This phase III trial aimed to confirm the superiority of weekly
      docetaxel and cisplatin over docetaxel monotherapy in elderly patients with
      advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy
      naive patients with stage III, stage IV, or recurrent NSCLC age >= 70 years with
      a performance status of 0 or 1 who were considered unsuitable for bolus cisplatin
      administration were randomly assigned to receive docetaxel 60 mg/m(2) on day 1,
      every 3 weeks, or docetaxel 20 mg/m(2) plus cisplatin 25 mg/m(2) on days 1, 8,
      and 15, every 4 weeks. The primary end point was overall survival (OS). RESULTS:
      In the first interim analysis, OS of the doublet arm was inferior to that of the
      monotherapy arm (hazard ratio [HR], 1.56; 95% CI, 0.98 to 2.49), and the
      predictive probability that the doublet arm would be statistically superior to
      the monotherapy arm on final analysis was 0.996%, which led to early study
      termination. In total, 276 patients with a median age of 76 years (range, 70 to
      87 years) were enrolled. At the updated analysis, the median survival time was
      14.8 months for the monotherapy arm and 13.3 months for the doublet arm (HR,
      1.18; 95% CI, 0.83 to 1.69). The rates of grade >= 3 neutropenia and febrile
      neutropenia were higher in the monotherapy arm, and those of anorexia and
      hyponatremia were higher in the doublet arm. CONCLUSION: This study failed to
      demonstrate any survival advantage of weekly docetaxel plus cisplatin over
      docetaxel monotherapy as first-line chemotherapy for advanced NSCLC in elderly
      patients.

PMID- 25584006
TI  - Reply to G. Spitzer and M.A. Socinski, F. Zhou et al, and B. Biswas.

PMID- 25584005
TI  - Expanded RAS: refining the patient population.

PMID- 25584007
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors in patients with EGFR
      wild-type lung cancer: when there is a target, there is a targeted drug.

PMID- 25584009
TI  - Reply to G. Spitzer and M.A. Socinski.

PMID- 25584010
TI  - Treatment selection and outcomes in early-stage classical Hodgkin lymphoma:
      analysis of the National Cancer Data Base.
AB  - PURPOSE: The choice between combined-modality therapy (CMT) and chemotherapy
      alone for early-stage Hodgkin lymphoma (HL) remains controversial. Our objective
      was to define factors affecting treatment selection and resulting survival
      outcomes in the United States. PATIENTS AND METHODS: We identified 20,600
      patients treated with CMT or chemotherapy between 2003 and 2011 from the National
      Cancer Data Base. Factors affecting treatment selection were studied in a mixed
      effects logistic model. Survival outcomes were compared using a propensity score
      analysis to account for indication bias. RESULTS: Only 49.5% of patients received
      CMT, and this proportion steadily declined between 2003 (59.4%) and 2011 (45.2%),
      particularly in younger patients. Apart from classical prognostic factors (age,
      stage, tumor location, histology, comorbidities), treatment selection was
      significantly influenced by sex, black race, distance to facility, and type of
      insurance. Uninsured patients had the lowest odds of receiving CMT. A significant
      random effect related to facility-specific treatment preference was also evident.
      Estimated 5-year overall survival (OS) was 89.6%, and relative survival (RS) was
      94.3%. After adjustment for guarantee-time and indication biases, CMT was
      associated with better OS (hazard ratio [HR], 0.61; 95% CI, 0.53 to 0.70) and RS
      (excess HR, 0.42; 95% CI, 0.33 to 0.54) than chemotherapy alone. This effect was
      without significant heterogeneity in subset analysis and was not sensitive to
      unobserved confounding. CONCLUSION: Socioeconomic factors affect selection of
      curative treatments in HL. Widespread abandonment of CMT beyond circumstances
      sanctioned by guidelines may affect survival. Further research should focus on
      developing strategies that minimize toxicity and access disparities without
      compromising survival.

PMID- 25584008
TI  - Prevalence and functional consequence of TP53 mutations in pediatric
      adrenocortical carcinoma: a children's oncology group study.
AB  - PURPOSE: Adrenocortical carcinoma (ACC) is a rare pediatric malignancy. It occurs
      in excess among individuals with the Li-Fraumeni syndrome, which results
      primarily from germline mutations in the TP53 gene. Prior series exploring
      frequencies of germline TP53 mutation among children with ACC have been small,
      geographically limited, or subject to referral bias. The functional consequence
      of mutations has not been related to phenotype. We provide a genotype-phenotype
      analysis of TP53 mutations in pediatric ACC and propose a model for tissue
      specific effects based on adrenocortical ontogeny. PATIENTS AND METHODS: Eighty
      eight consecutive, unrelated children with ACC, unselected for family history,
      underwent germline TP53 sequencing. Rate and distribution of mutations were
      identified. Functional analysis was performed for novel TP53 variants.
      Correlation with the International Agency for Research on Cancer p53 database
      further delineated mutational distribution, association with family history, and
      risk for multiple primary malignancies (MPMs). RESULTS: Germline mutations were
      present in 50% of children. These mutations did not correspond to the
      conventional hotspot mutations. There was a wide range of mutant protein
      function. Patients bearing alleles encoding protein with higher functionality
      were less likely to have a strong family cancer history, whereas those with
      greater loss of function had MPMs and/or positive family history. In patients
      with MPMs, ACC was the most frequent initial malignancy. Finally, we demonstrated
      age-dependent rates of TP53 mutation positivity. CONCLUSION: TP53 mutations are
      prevalent in children with ACC but decline with age. Mutations result in a broad
      spectrum of functional loss. Effect of individual mutations may predict carrier
      and familial disease penetrance with potentially broad implications for clinical
      surveillance and counseling.

PMID- 25584013
TI  - Microfluidics for High School Chemistry Students.
AB  - We present a laboratory experiment that introduces high school chemistry students
      to microfluidics while teaching fundamental properties of acid-base chemistry.
      The procedure enables students to create microfluidic systems using
      nonspecialized equipment that is available in high school classrooms and reagents
      that are safe, inexpensive, and commercially available. The experiment is
      designed to ignite creativity and confidence about experimental design in a high
      school chemistry class. This experiment requires a computer program (e.g.,
      PowerPoint), Shrinky Dink film, a readily available silicone polymer, weak acids,
      bases, and a colorimetric pH indicator. Over the span of five 45-min class
      periods, teams of students design and prepare devices in which two different pH
      solutions mix in a predictable way to create five different pH solutions. Initial
      device designs are instructive but rarely optimal. During two additional half
      class periods, students have the opportunity to use their initial observations to
      redesign their microfluidic systems to optimize the outcome. The experiment
      exposes students to cutting-edge science and the design process, and solidifies
      introductory chemistry concepts including laminar flow, neutralization of weak
      acids-bases, and polymers.

PMID- 25584014
TI  - The application of formyl group activation of bromopyrrole esters to formal
      syntheses of lycogarubin C, permethyl storniamide A and lamellarin G trimethyl
      ether.
AB  - Lycogarubin C, permethyl storniamide A and lamellarin G trimethyl ether are
      pyrrole containing, natural products, which exhibit interesting biological
      properties. Such properties include anti-tumor activity on a variety of cancer
      cell lines including those that confer drug resistance, inhibition of HIV
      integrase and vascular disrupting activity. We now describe the use of methyl and
      ethyl 3-bromo-2-formylpyrrole-5-carboxylate as building blocks for the formal
      synthesis of these three highly functionalized, bioactive pyrroles. These new
      building blocks will now provide ready access to the natural products and many
      novel analogs due to the ability to easily modify positions 2,3,4 and 5 of the
      pyrrole core.

PMID- 25584011
TI  - Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in
      mice.
AB  - Progressive tissue fibrosis is a cause of major morbidity and mortality.
      Pulmonary fibrosis is an epithelial-mesenchymal disorder in which TGF-beta1 plays
      a central role in pathogenesis. Here we show that follistatin-like 1 (FSTL1)
      differentially regulates TGF-beta and bone morphogenetic protein signaling,
      leading to epithelial injury and fibroblast activation. Haplodeletion of Fstl1 in
      mice or blockage of FSTL1 with a neutralizing antibody in mice reduced bleomycin
      induced fibrosis in vivo. Fstl1 is induced in response to lung injury and
      promotes the accumulation of myofibroblasts and subsequent fibrosis. These data
      suggest that Fstl1 may serve as a novel therapeutic target for treatment of
      progressive lung fibrosis. 

PMID- 25584015
TI  - Making Ends Meet After Prison.
AB  - Former prisoners are at high risk of economic insecurity due to the challenges
      they face in finding employment and to the difficulties of securing and
      maintaining public assistance while incarcerated. This study examines the
      processes through which former prisoners attain economic security, examining how
      they meet basic material needs and achieve upward mobility over time. It draws on
      unique qualitative data from in-depth, unstructured interviews with a sample of
      former prisoners followed over a two to three year period to assess how subjects
      draw upon a combination of employment, social supports, and public benefits to
      make ends meet. Findings reveal considerable struggle among our subjects to meet
      even minimal needs for shelter and food, although economic security and stability
      could be attained when employment or public benefits were coupled with familial
      social support. Sustained economic security was rarely achieved absent either
      strong social support or access to long-term public benefits. However, a select
      few were able to leverage material support and social networks into trajectories
      of upward mobility and economic independence. Policy implications are discussed.

PMID- 25584012
TI  - Bee venom processes human skin lipids for presentation by CD1a.
AB  - Venoms frequently co-opt host immune responses, so study of their mode of action
      can provide insight into novel inflammatory pathways. Using bee and wasp venom
      responses as a model system, we investigated whether venoms contain CD1-presented
      antigens. Here, we show that venoms activate human T cells via CD1a proteins.
      Whereas CD1 proteins typically present lipids, chromatographic separation of
      venoms unexpectedly showed that stimulatory factors partition into protein
      containing fractions. This finding was explained by demonstrating that bee venom
      derived phospholipase A2 (PLA2) activates T cells through generation of small
      neoantigens, such as free fatty acids and lysophospholipids, from common
      phosphodiacylglycerides. Patient studies showed that injected PLA2 generates
      lysophospholipids within human skin in vivo, and polyclonal T cell responses are
      dependent on CD1a protein and PLA2. These findings support a previously unknown
      skin immune response based on T cell recognition of CD1a proteins and lipid
      neoantigen generated in vivo by phospholipases. The findings have implications
      for skin barrier sensing by T cells and mechanisms underlying phospholipase
      dependent inflammatory skin disease. 

PMID- 25584017
TI  - Development and Coherence of Beliefs About Disease Causality and Prevention.
AB  - Guided by a naive theories perspective on the development of thinking about
      disease, this study of 188 children aged 6 to 18 examined knowledge of HIV/AIDS
      causality and prevention using parallel measures derived from open-ended and
      structured interviews. Knowledge of both risk factors and prevention rules, as
      well as conceptual understanding of AIDS causality, increased with age. Younger
      children displayed more advanced knowledge in response to structured questions
      than in response to open-ended questions. Contrary to hypothesis, knowledge of
      causality was not more advanced than knowledge of prevention in elementary
      school. Moreover, correlations between the two types of knowledge were often
      nonsignificant except when the same method was used to assess both. Thus,
      methodology matters in assessing children's knowledge of disease, children's
      intuitive thinking is not consistently coherent, and it may be safest to educate
      children explicitly about sound prevention rules rather than assume they will
      infer the rules themselves from information about a disease's causes.

PMID- 25584016
TI  - GENETIC CAUSES OF DILATED CARDIOMYOPATHY.
AB  - Dilated cardiomyopathy is a disease of the myocardium characterized by left
      ventricular dilatation and/or dysfunction, affecting both adult and pediatric
      populations. Almost half of cases are genetically determined with an autosomal
      pattern of inheritance. Up to 40 genes have been identified affecting proteins of
      a wide variety of cellular structures such as the sarcomere, the nuclear
      envelope, the cytoskeleton, the sarcolemma and the intercellular junction. Novel
      gene mutations have been recently identified thanks to advances in next
      generation sequencing technologies. Genetic screening is an essential tool for
      early diagnosis, risk assessment, prognostic stratification and, possibly,
      adoption of primary preventive measures in affected patients and their
      asymptomatic relatives. The purpose of this article is to review the genetic
      basis of DCM, the known genotype-phenotype correlations, the role of current
      genetic sequencing techniques in the discovery of novel pathogenic gene mutations
      and new therapeutic perspectives.

PMID- 25584018
TI  - The relationship between Graves' ophthalmopathy and dry eye syndrome.
AB  - BACKGROUND: A complex relationship between Graves' ophthalmopathy (GO) and dry
      eye syndrome exists. New research brings more insight into the association
      between these two diseases. METHODS: A review of the literature was conducted
      using the query terms "Graves' Ophthalmopathy", "Thyroid Eye Disease", and "Dry
      Eye" in MedLine (PubMed) and Scopus. A total of 55 papers were reviewed. Case
      reports were excluded. CONCLUSION: This review paper shows the close relationship
      between dry eye syndrome and GO. The underlying mechanisms behind their
      association suggest mechanical impairment of orbital muscles and immune-mediated
      lacrimal gland dysfunction as the causes of dry eye in GO patients. However,
      there are a variety of treatment options available for patients with GO with
      signs of dry eye, which help combat this issue.

PMID- 25584019
TI  - Cisplatin-induced hyponatremia in malignancy: comparison between brand-name and
      generic formulation.
AB  - INTRODUCTION: Widespread use of generic drugs is considered to be indispensable
      if reductions in total health care costs are to be achieved, but the market share
      of such drugs remains low. In general, generic drugs have the same active
      ingredients as brand-name drugs, but this is not always the case. Thus, toxicity
      profiles may vary when brand-name and generic drugs are compared. We
      retrospectively investigated the incidence of hyponatremia in patients receiving
      brand-name cisplatin (CDDP) and a generic counterpart thereof. METHODS: We
      reviewed the medical records of patients treated with brand-name CDDP (n=53) and
      a generic formulation (n=26), and compared the incidences of hyponatremia and
      renal toxicity. Toxicities were graded using the Common Terminology Criteria for
      Adverse Events, version 4.0. Differences between groups were evaluated using the
      Student's t-test, and the odds ratio for hyponatremia was estimated via logistic
      regression analysis. RESULTS: Serum creatinine levels after chemotherapy
      increased significantly in both the brand-name and generic CDDP groups; no
      significant difference was evident between the two groups. Hyponatremia of grade
      3 or above developed in 30.7% of the generic CDDP group compared to 15.1% of the
      brand-name CDDP group (P=0.011). Multivariate analysis showed that the use of
      generic CDDP increased the incidence of hyponatremia (odds ratio =5.661, 95%
      confidence interval =1.403-22.839; P=0.015). CONCLUSION: Oncologists should be
      aware that use of a generic CDDP might be associated with more hyponatremia than
      would use of brand-name CDDP.

PMID- 25584020
TI  - Functional characterization of a competitive peptide antagonist of p65 in human
      macrophage-like cells suggests therapeutic potential for chronic inflammation.
AB  - Glucocorticoid-induced leucine zipper (GILZ) is a glucocorticoid responsive
      protein that links the nuclear factor-kappa B (NFkappaB) and the glucocorticoid
      signaling pathways. Functional and binding studies suggest that the proline-rich
      region at the carboxy terminus of GILZ binds the p65 subunit of NFkappaB and
      suppresses the immunoinflammatory response. A widely-used strategy in the
      discovery of peptide drugs involves exploitation of the complementary surfaces of
      naturally occurring binding partners. Previously, we observed that a synthetic
      peptide (GILZ-P) derived from the proline-rich region of GILZ bound activated p65
      and ameliorated experimental encephalomyelitis. Here we characterize the
      secondary structure of GILZ-P by circular dichroic analysis. GILZ-P adopts an
      extended polyproline type II helical conformation consistent with the structural
      conformation commonly observed in interfaces of transient intermolecular
      interactions. To determine the potential application of GILZ-P in humans, we
      evaluated the toxicity and efficacy of the peptide drug in mature human
      macrophage-like THP-1 cells. Treatment with GILZ-P at a wide range of
      concentrations commonly used for peptide drugs was nontoxic as determined by cell
      viability and apoptosis assays. Functionally, GILZ-P suppressed proliferation and
      glutamate secretion by activated macrophages by inhibiting nuclear translocation
      of p65. Collectively, our data suggest that the GILZ-P has therapeutic potential
      in chronic CNS diseases where persistent inflammation leads to neurodegeneration
      such as multiple sclerosis and Alzheimer's disease. 

PMID- 25584021
TI  - Bevacizumab treatment in the elderly patient with metastatic colorectal cancer.
AB  - Metastatic colorectal cancer (mCRC), like many cancers, is primarily a disease of
      elderly people. Despite this prevalence, such patients are often excluded from
      randomized trials or represent a minority of enrolled patients. Moreover, the
      criteria for establishing benefit or side effects of treatment strategies in this
      population are uncertain and not well recognized. Bevacizumab improves the
      outcome of mCRC when used in combination with standard first-line and second-line
      chemotherapy and beyond the first disease progression when given with a
      chemotherapy backbone different from that used in the precedent line. The
      particular toxicity profile of this antiangiogenesis agent (in particular
      hypertension, thromboembolic events, hemorrhage, and renal failure) may
      discourage its use in elderly patients with comorbidities. Data from subgroup
      analyses of randomized trials and the results of recent cohort studies suggest a
      significant benefit from the addition of bevacizumab to standard chemotherapy for
      elderly patients comparable with that observed in younger patients, except for
      the increased risk for thromboembolic events. Age alone should not be a barrier
      to use of bevacizumab, and further research with a more complete geriatric
      assessment should investigate the role of bevacizumab in elderly patients with
      mCRC to avoid undertreatment of this patient population due to a historical
      conservative approach. 

PMID- 25584022
TI  - Family caregivers' role implementation at different stages of dementia.
AB  - PURPOSE: The purpose of this study was to explore family caregivers' role
      implementation experiences at different stages of dementia. PATIENTS AND METHODS:
      For this cross-sectional, exploratory study, 176 dyads of family caregivers and
      their community-dwelling elderly relatives with dementia were recruited from the
      neurological clinics of a medical center in Taiwan. The Family Caregiving
      Inventory was used to assess family caregivers for caregiving activities, role
      strain, role preparation, and help from others at different stages of care
      receivers' dementia. RESULTS: Family caregivers' caregiving activities were
      related to patients' stages of dementia. For patients with mild dementia,
      caregivers provided more assistance in transportation and housekeeping. In
      addition to these two activities, family caregivers of patients with moderate
      dementia provided more assistance with mobility and protection. For patients with
      severe dementia, family caregivers provided more assistance with personal care,
      mobility and protection, transportation, and housekeeping. Overall, family
      caregivers reported having some preparation to provide care; the most difficult
      caregiving activity was identified as managing behavioral problems. CONCLUSION:
      This study's results provide a knowledge base for designing dementia stage
      specific interventions in clinical practice and developing community-based, long
      term care systems for families of patients with dementia.

PMID- 25584023
TI  - Perceived barriers and facilitators to increasing physical activity among people
      with musculoskeletal disorders: a qualitative investigation to inform
      intervention development.
AB  - PURPOSE: Musculoskeletal conditions can impair people's ability to undertake
      physical activity as they age. The purpose of this qualitative study was to
      investigate perceived barriers and facilitators to undertaking physical activity
      reported by patients accessing ambulatory hospital clinics for musculoskeletal
      disorders. PATIENTS AND METHODS: A questionnaire with open-ended items was
      administered to patients (n=217, 73.3% of 296 eligible) from three clinics
      providing ambulatory services for nonsurgical treatment of musculoskeletal
      disorders. The survey included questions to capture the clinical and demographic
      characteristics of the sample. It also comprised two open-ended questions
      requiring qualitative responses. The first asked the participant to describe
      factors that made physical activity more difficult, and the second asked which
      factors made it easier for them to be physically active. Participants' responses
      to the two open-ended questions were read, coded, and thematically analyzed
      independently by two researchers, with a third researcher available to arbitrate
      any unresolved disagreement. RESULTS: The mean (standard deviation) age of
      participants was 53 (15) years; n=113 (52.1%) were male. A total of 112 (51.6%)
      participants reported having three or more health conditions; n=140 (64.5%) were
      classified as overweight or obese. Five overarching themes describing perceived
      barriers for undertaking physical activity were "health conditions", "time
      restrictions", "poor physical condition", "emotional, social, and psychological
      barriers", and "access to exercise opportunities". Perceived physical activity
      facilitators were also aligned under five themes, namely "improved health state",
      "social, emotional, and behavioral supports", "access to exercise environment",
      "opportunities for physical activities", and "time availability". CONCLUSION: It
      was clear from the breadth of the data that meaningful supports and interventions
      must be multidimensional. They should have the capacity to address a variety of
      physical, functional, social, psychological, motivational, environmental,
      lifestyle, and other perceived barriers. It would appear that for such
      interventions to be effective, they should be flexible enough to address a
      variety of specific concerns.

PMID- 25584024
TI  - The Healthy Aging Brain Care (HABC) Monitor: validation of the Patient Self
      Report Version of the clinical tool designed to measure and monitor cognitive,
      functional, and psychological health.
AB  - BACKGROUND: Primary care providers need an inexpensive, simple, user-friendly,
      easily standardized, sensitive to change, and widely available multidomain
      instrument to measure the cognitive, functional, and psychological symptoms of
      patients suffering from multiple chronic conditions. We previously validated the
      Caregiver Report Version of the Healthy Aging Brain Care Monitor (HABC Monitor)
      for measuring and monitoring the severity of symptoms through caregiver reports.
      The purpose of this study was to assess the reliability and validity of the
      Patient Self-Report Version of the HABC Monitor (Self-Report HABC Monitor).
      DESIGN: Cross-sectional study. SETTING: Primary care clinics affiliated with a
      safety net urban health care system in Indianapolis, Indiana, USA. SUBJECTS: A
      total of 291 subjects aged >=65 years with a mean age of 72.7 (standard deviation
      6.2) years, 76% female, and 56% African Americans. ANALYSIS: Psychometric
      validity and reliability of the Self-Report HABC Monitor. RESULTS: Among 291
      patients analyzed, the Self-Report HABC Monitor demonstrated excellent fit for
      the confirmatory factor analysis model (root mean square error of approximation
      =0.030, comparative fit index =0.974, weighted root mean square residual =0.837)
      and good internal consistency (0.78-0.92). Adequate convergent-divergent validity
      (differences between the Telephone Interview for Cognitive Status test-based
      cognitive function impairment versus nonimpairment groups) was demonstrated only
      when patients were removed from analysis if they had both cognitive function test
      impairment and suspiciously perfect self-report HABC Monitor cognitive floor
      scores of 0. CONCLUSION: The Self-Report HABC Monitor demonstrates good
      reliability and validity as a clinically practical multidimensional tool for
      measuring symptoms. The tool can be used along with its caregiver version to
      provide useful feedback (via monitoring of symptoms) for modifying care plans.
      Determining the validity of HABC Monitor scores from patients who self-report a
      perfect cognitive score of 0 requires cognitive function test results (eg,
      Telephone Interview for Cognitive Status or Mini Mental State Examination) or
      Caregiver Report HABC Monitor scores or further clinical examination to rule out
      the possibility that the patient is denying or unaware of their cognitive
      symptoms.

PMID- 25584025
TI  - Predictors of improved functional outcome in elderly inpatients after
      rehabilitation: a retrospective study.
AB  - PURPOSE: The number of elderly inpatients has been steadily increasing worldwide.
      However, the ability to predict the degree of improvement of functional capacity
      after comprehensive examination of elderly inpatients is still lacking. The
      purpose of this study was to investigate the predictors of improved functional
      outcome after rehabilitation of elderly inpatients. METHODS: We performed a
      retrospective cohort study with 1,079 patients (age <70 years: N=331, age >=70
      years: N=748) who had been admitted to Tottori Municipal Hospital. Functional
      Independence Measure (FIM) scores were measured both at admission and discharge
      to calculate FIM gain and efficiency. Of these patients, 262 patients had oral
      examinations on admission. The Mann-Whitney U-test or chi-square test was used
      for statistical analyses. Conditional logistic regression analysis was used to
      compute the odds ratio (OR) and 95% confidence interval (CI). Cut-off values of
      FIM scores to determine if elderly inpatients were able to return home after
      discharge were determined using a receiver operating characteristic curve.
      RESULTS: FIM scores, including FIM gain and efficiency, of elderly patients were
      significantly lower than those of middle-aged patients. Inability to close the
      lips and dysfunctional tongue movement, but not the loss of teeth, were
      correlated with a reduced improvement of FIM scores. Cognitive impairment and
      aspiration pneumonia, but not cerebrovascular disease, were also correlated with
      a reduced improvement of FIM scores. Interestingly, FIM scores were significantly
      lower in patients with both cerebrovascular disease and a loss of posterior
      occlusion. Factors shown to have a significant impact on the improvement of FIM
      scores included the stable posterior occlusion (OR: 2.23, 95% CI: 1.2-4.1),
      closed lips (OR: 5.15, 95% CI: 2.3-11.7), functional tongue movement (OR: 5.74,
      95% CI: 3.0-11.0), presence of cognitive impairment (OR: 0.31, 95% CI: 0.17
      0.49), and presence of aspiration pneumonia (OR: 0.27, 95% CI: 0.15-0.51).
      CONCLUSION: Age and disorder of oral function may be significant predictors of
      improved functional capacity after rehabilitation for elderly inpatients.

PMID- 25584026
TI  - Theory of Mind in Schizophrenia and Asperger's Syndrome: Relationship with
      Negative Symptoms.
AB  - OBJECTIVE: Although previous studies have shown that the theory of mind (ToM)
      ability is impaired in Asperger's Syndrome (AS) and in schizophrenia, few
      controlled studies compared the ToM performance between the two disorders.
      Besides, the relationship between the degree of ToM impairment and symptom
      dimensions is unclear, and presence of ToM impairment in remitted patients with
      schizophrenia is controversial. Here, we tested the hypothesis that schizophrenia
      patients with prominent negative symptoms were closer to AS patients and
      different than schizophrenia patients without prominent negative symptoms and
      healthy controls in terms of ToM functioning. METHOD: Fourteen patients with AS,
      20 with schizophrenia and 20 healthy controls, matched by age, educational level
      and IQ scores were enrolled. AS was diagnosed according to the DSM-IV criteria
      and independently confirmed by two psychiatrists. Schizophrenia patients were
      diagnosed by the Turkish version of Structured Clinical Interview for DSM-IV
      Diagnosis (SCID-I) and symptom severity was evaluated with the Scale for the
      Assessment of Negative and Positive Symptoms. Schizophrenia group consisted of
      clinically stable patients. The ToM battery included stories to assess first and
      second order false belief tasks (ToM1 and ToM2). The full-scale IQ, Verbal
      Comprehension, Freedom from Distractibility and Perceptual Organization scores
      were assessed by Weschler Adult Intelligence Scale-Revised (WAIS-R). Non
      parametric tests were used to compare the neuropsychological performances of the
      three groups. In order to investigate whether schizophrenia patients with
      prominent negative symptoms were similar to AS patients, schizophrenia patients
      were divided into high (Sch-HN) and low (Sch-LN) negative-symptom subgroups by
      median split. For these four groups (AS, Sch-HN, Sch-LN, and controls) between
      group comparisons were performed. Correlations between the clinical measures and
      ToM performance were assessed by Spearman correlation test. RESULTS: AS and
      schizophrenia patients performed significantly worse than controls in the ToM2
      task, while the AS group had worse ToM1 performance than both schizophrenia
      patients and healthy controls. The Sch-HN subgroup had significantly lower ToM2
      scores than the Sch-LN patients, and worse ToM1 functioning than the controls.
      CONCLUSIONS: These results suggest that clinically stable schizophrenia patients
      have ToM impairments. Sch-HN group performed comparably poorly as the AS group,
      while the Sch-LN group was relatively spared. The most profoundly impaired
      patients with schizophrenia in terms of ToM functioning were represented by those
      with high negative symptoms (Sch-HN). Similar to AS, as a neurodevelopmental
      impairment, these patients may not have developed ToM ability, or they may have
      lost their ToM capacity as a result of a neurodegenerative process during the
      illness. Supplementary studies using other methods (e.g., neuroimaging,
      neurophysiology) may highlight the brain regions that are affected differentially
      in AS and schizophrenia, the relationship of ToM impairments and negative
      symptoms, and the role of ToM impairments in the neurodevelopmental or
      neurodegenerative hypothesis of schizophrenia.

PMID- 25584027
TI  - Comparison of serum granulocyte colony-stimulating factor levels between preterm
      and term births.
AB  - OBJECTIVE: Preterm birth (PTB) is the major obstetric problem in developed
      countries, accounting for the majority of neonatal mortality and morbidity.
      Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that
      mediates the increase in leukocytes in pregnancy and may play a role in
      placentation. We aimed to investigate the differences of serum G-CSF levels
      between subsequent spontaneous PTB and term-delivered healthy pregnant women.
      MATERIAL AND METHODS: Serum samples, collected from total of 600 singleton
      otherwise healthy pregnants at 24-28 weeks of gestation during a routine
      antenatal visit, were used to assess G-CSF levels; 40 of the total pregnants who
      delivered their infants spontaneously after preterm labor before 37 weeks of
      gestation were selected as the study group. Also, 120 pregnants were selected as
      a control group using a 1/3 ratio. Student's t-test, chi-square test, Mann
      Whitney U-tests, and ROC curve analysis for prediction of PTB were used for the
      comparison of groups. P<0.05 was accepted as statistically significant. RESULTS:
      There was no significant difference in maternal serum G-CSF levels between the
      study and control groups (p=0.28) but maternal white blood cell (WBC) count was
      significantly different between them (p=0.00). In addition, G-CSF was
      insufficient in the prediction of PTB (AUC=0.419). In the preterm and term
      groups, no correlation was found between WBC and G-CSF (p=0.165 vs. p=0.703).
      CONCLUSION: There were no differences in serum levels of G-CSF between term- and
      preterm-delivered pregnants. There was no predictive role for serum G-CSF in PTB.

PMID- 25584028
TI  - Changes in first trimester screening test parameters in pregnancies complicated
      by placenta previa and association with hyperemesis gravidarum.
AB  - OBJECTIVE: To assess the possible changes in first trimester screening test
      parameters in pregnancies complicated with placenta previa and to determine
      whether there is an association between hyperemesis gravidarum and placenta
      previa. MATERIAL AND METHODS: A total of 131 singleton spontaneously conceived
      pregnancies that were complicated by placenta previa and delivered between May
      2006 and May 2013 were evaluated from birth charts. Ninety patients without
      placenta previa were selected amongst patients who delivered within the same
      period of time as the control group. Cases of low lying placenta (n=52) within
      the study group were assessed as a separate group. The rest of the cases was
      considered to be in a different group. RESULTS: Beta human chorionic gonadotropin
      (BhCG) multiples of medians (MoMs) and nuchal translucency (NT) MoMs were
      significantly higher in the placenta previa group in comparison with the low
      lying placenta and control groups. Apgar scores at both the 1st and 5th minutes
      were significantly lower in the placenta previa group. Hyperemesis gravidarum was
      found to be significantly more frequent in the placenta previa group. CONCLUSION:
      The prevalence of hyperemesis gravidarum in the first trimester is higher in
      pregnancies complicated by placenta previa. Paying more attention to the
      development of placenta previa in the routine pregnancy follow-up of patients
      with hyperemesis gravidarum could be considered.

PMID- 25584029
TI  - An intensive care approach to posterior reversible encephalopathy syndrome
      (PRES): An analysis of 7 cases.
AB  - OBJECTIVE: The aim of this study was to retrospectively evaluate the intensive
      care unit treatments applied to obstetrics patients with a diagnosis of posterior
      reversible encephalopathy syndrome (PRES). MATERIAL AND METHODS: The cases of 7
      pregnant patients who had been diagnosed with PRES between July 2011 and July
      2013 were retrospectively reviewed. The patients' clinical data, brain magnetic
      resonance imaging (MRI) images before and after treatment, and neuropsychological
      tests were evaluated. RESULTS: Five out of 7 patients had eclampsia, 1 patient
      had severe preeclampsia, and 1 patient developed HELLP syndrome secondary to
      PRES. Calcium channel blockers and beta-blockers were used as antihypertensive
      treatment. All patients were treated with parenteral magnesium sulfate. In
      addition, sodium thiopental was given to control sedation and convulsions in all
      patients except 1. The neurological and radiological findings of all cases
      treated in the intensive care unit improved. CONCLUSION: Posterior reversible
      encephalopathy syndrome is a clinical condition with a multifactorial etiology
      and can result in different clinical findings. Radiological imaging techniques
      can be used for the diagnosis of PRES. Pregnancy and the postpartum period often
      lead to this syndrome. In some cases, PRES can cause irreversible neurological
      deficits or death. For patients with severe radiological findings, early
      diagnosis and thiopental infusion, in addition to treatment with antihypertensive
      agents and magnesium sulfate, may lead to quicker and more effective recovery
      from clinical manifestations. We suggest supplementation of standard treatment
      with early thiopental infusion.

PMID- 25584030
TI  - Maternal mortality and derivations from the WHO near-miss tool: An institutional
      experience over a decade in Southern India.
AB  - OBJECTIVE: Preceding the use of World Health Organization (WHO) near-miss
      approach in our institute for the surveillance of Severe Maternal Outcome (SMO),
      we pilot-tested the tool on maternal death cases that took place over the last 10
      years in order to establish its feasibility and usefulness at the institutional
      level. MATERIAL AND METHODS: This was a retrospective review of maternal deaths
      in Christian Medical College Vellore, India, over a decade. Cases were recorded
      and analyzed using the WHO near-miss tool. The International Classification of
      Diseases, 10(th) Revision was used to define and classify maternal mortality.
      RESULTS: There were 98,139 total births and 212 recorded maternal deaths. Direct
      causes of mortality constituted 46.96% of total maternal deaths, indirect causes
      constituted 51.40%, and unknown cases constituted 1.9%. Nonobstetrical cause
      (48.11%) is the single largest group. Infections (19.8%) other than puerperal
      sepsis remain an important group, with pulmonary tuberculosis, scrub typhus, and
      malaria being the leading ones. According to the WHO near-miss criteria,
      cardiovascular and respiratory dysfunctions are the most frequent organ
      dysfunctions. Incidence of coagulation dysfunction is seen highest in obstetrical
      hemorrhage (64%). All women who died had at least one organ dysfunction; 90.54%
      mothers had two- and 38.52% had four- or more organ involvement. CONCLUSION: The
      screening questions of the WHO near-miss tool are particularly instrumental in
      obtaining a comprehensive assessment of the problem beyond the International
      Classification of Diseases-Maternal Mortality and establish the need for
      laboratory-based identification of organ dysfunctions and prompt availability of
      critical care facilities. The process indicators, on the other hand, inquire
      about the basic interventions that are more or less widely practiced and
      therefore give no added information at the institutional level.

PMID- 25584031
TI  - Effect of tamoxifen on ovarian reserve: A randomized controlled assessor-blind
      trial in a mouse model.
AB  - OBJECTIVE: To determine whether tamoxifen (TMX) exposure causes a permanent
      decrease in ovarian reserve. MATERIAL AND METHODS: A randomized controlled
      assessor-blind trial including 30 adult female inbred BALB/C mice. Fifteen mice
      in the TMX group were given a single 0.1-mg dose of TMX intraperitoneally.
      Fifteen mice in the control group were given a single dose of the vehicle at the
      same volume intraperitoneally. Two cycles later, blood samples were collected for
      determination of anti-Mullerian hormone (AMH) levels, and the mice were
      sacrificed. After gonadectomy, ovarian size was measured, and follicles were
      counted under light microscopy. RESULTS: Median serum AMH levels were 6.53 and
      6.14 ng/ml in the control and TMX groups, respectively (p=0.03). Ovarian size was
      significantly decreased in the TMX group. While the number of primordial (9 vs
      8), primary (6 vs 3), and secondary (4.5 vs 5) follicles were similar, there were
      significantly fewer preantral (11.5 vs 6, p<0.01) and antral (2 vs 1, p: 0.03)
      follicles, as well as corpora lutea (6 vs 3, p: 0.04), in the TMX group than in
      the control group. The number of atretic (2.5 vs 5, p: 0.048) follicles was
      increased in the TMX group. CONCLUSION: Tamoxifen administration leads to
      arrested growth of gonadotropin-sensitive follicles, while insensitive follicles
      can remain unaffected. TMX is merely an endocrine disruptor, and it does not
      cause a decrease in primordial follicle pool.

PMID- 25584032
TI  - Effects of different anesthesia protocols on lactation in the postpartum period.
AB  - OBJECTIVE: Many factors can influence the secretion of breast milk. Cesarean
      section is a risk factor for late onset of breastfeeding. MATERIAL AND METHODS:
      In our study, we compared the lactation process by mothers who underwent elective
      cesarean section under general anesthesia, spinal anesthesia, epidural
      anesthesia, and normal birth; 84 patients between 18-40 years of age with a risk
      of ASA I-II were included. Randomly patients were divided into four groups: group
      G (general anesthesia, n:21), group S (spinal anesthesia, n:21), group E
      (epidural anesthesia, n:21), and group V (vaginal birth, without anesthesia,
      n:21). Oxytocin and prolactin values of all patients before and after operation
      or birth were recorded. In addition the initiation time of lactation after
      delivery or cesarean section were recorded. RESULTS: In all groups, there were no
      significant differences among hormone levels in the prepartum period (p=0.350).
      Prolactin levels in group G (p=0.011) and oxytocin levels in group V (p=0.012) in
      the postpartum period were significantly higher than in the other groups. The
      start of lactation was significantly delayed in group G (p=0.003). CONCLUSION: We
      consider that the onset time of lactation is delayed in patients undergoing
      cesarean section with general anesthesia when compared with patients who undergo
      cesarean section with spinal and epidural anesthesia and with patients who
      undergo normal vaginal birth. Because of the delay of awakening and recovery of
      cognitive functions in general anesthesia, communication between the mother and
      the newborn is delayed and so is the lactation.

PMID- 25584034
TI  - Left lateral position and common gynecologic examining position in anal manometry
      measurements for evaluation of urogynecologic patients.
AB  - OBJECTIVE: The aim of this study is to compare the anometrical parameters
      obtained in the left lateral position, which is the conventional position of anal
      manometry, with the same measurements taken in the common gynecologic examining
      position (45 degrees  sitting position in a birthing chair with maximum hip
      flexion). MATERIAL AND METHODS: Twenty-one patients with lower urinary tract
      symptoms (LUTS) were enrolled into this prospective cohort study. Basal mean
      resting pressure (BMRP), maximum squeeze pressure (MSP), rectal sensation, rectal
      compliance, and recto-anal inhibitory reflex (RAIR) were compared between the
      gynecologic examining position and left lateral position. RESULTS: There was no
      statistically difference between the anal manometric measurements of the left
      lateral and gynecologic examining positions (paired t-test, p>.05). CONCLUSION:
      It can be concluded that it seems to be unnecessary to change the examination
      chair and/or patient position in urogynecological patients who need an anorectal
      assessment.

PMID- 25584033
TI  - The effects of subchorionic hematoma on pregnancy outcome in patients with
      threatened abortion.
AB  - OBJECTIVE: To assess the effects of ultrasonographically detected subchorionic
      hematomas on pregnancy outcomes in patients with vaginal bleeding within the
      first half of pregnancy. MATERIAL AND METHODS: Patients diagnosed with threatened
      abortion due to painless vaginal bleeding and who were followed up in an in
      patient service during the first vaginal bleeding between January 2009 and
      December 2010 were included in this retrospective cohort study. Patients were
      divided into two groups according to the presence of subchorionic hematoma.
      Miscarriage rates and pregnancy outcomes of ongoing pregnancies were compared
      between the groups. RESULTS: There were no statistically significant differences
      between the groups regarding demographic parameters, including age, parity,
      previous miscarriage history, and gestational age at first vaginal bleeding.
      While 13 of 44 pregnancies (29.5%) with subchorionic hematoma resulted in
      miscarriage, 25 of 198 pregnancies (12.6%) without subchorionic hematoma resulted
      in miscarriage (p=.010). The gestational age at miscarriage and the duration
      between first vaginal bleeding and miscarriage were similar between the groups.
      The outcome measures of ongoing pregnancies, such as gestational week at
      delivery, birth weight, and delivery route, were also similar between the groups.
      CONCLUSION: Ultrasonographically detected subchorionic hematoma increases the
      risk of miscarriage in patients with vaginal bleeding and threatened abortion
      during the first 20 weeks of gestation. However, it does not affect the pregnancy
      outcome measures of ongoing pregnancies.

PMID- 25584035
TI  - Maternal and obstetrical factors associated with a successful trial of vaginal
      birth after cesarean section.
AB  - OBJECTIVE: To detect the maternal and obstetrical factors associated with
      successful trial of vaginal birth among women with a previous cesarean delivery.
      MATERIAL AND METHODS: A total of 122 women who were eligible for a trial of labor
      after cesarean section (TOLAC) according to departmental protocol were included
      in this comparative prospective study. After informed consent, the women included
      in this study were subjected to a thorough history to detect maternal and
      obstetric characteristics and a standard examination to estimate fetal weight,
      engagement of the fetal head, intra-partum features of fetal membranes, and
      cervical dilatation. After delivery, data on duration of labor, labor
      augmentation, mode of delivery, birth outcome, and neonatal intensive care (NICU)
      admission were recorded and analyzed. RESULTS: Trial of labor after cesarean
      section was successful in 72.13% and was unsuccessful in 27.87%. Body mass index
      (BMI) was significantly lower in the successful TOLAC group compared to the
      unsuccessful group (23.8+/-0.03 versus 26.2+/-0.02 kg/m(2)), and the number of
      women with BMI >25 kg/m(2) was significantly high in the unsuccessful group;
      also, mean gestational age was significantly lower in the successful TOLAC group
      compared to the unsuccessful group (37.5+/-0.04 versus 38.5+/-0.03 weeks), and
      the number of women admitted in labor with gestation >=40 weeks was significantly
      high in the unsuccessful group. The number of women admitted with >2/5 of fetal
      head palpable abdominally and fetal head station >=-2 was significantly high in
      the unsuccessful TOLAC group. CONCLUSION: In carefully selected cases, TOLAC is
      safe and often successful. Presence of BMI >25 kg/m(2), gestation >=40 weeks, and
      vertex station >=-2 were risk factors for unsuccessful TOLAC.

PMID- 25584037
TI  - Complete hydatidiform mole presenting as placenta previa in a twin pregnancy with
      a coexisting normal foetus: Case report.
AB  - We present a case of a patient with a complete hydatidiform mole co-existing with
      a normal foetus (CMCF) who had a caesarean section in week 32 of gestation,
      resulting in a live female infant weighing 1590 grams. The mother, with a normal
      bleeding pattern, did not require any surgical intervention. She was discharged
      from hospital on the third post-operative day. Premature termination is
      recommended in this type of pregnancy because of the risks associated with molar
      pregnancies. However, with the close follow-up of these pregnancies, good
      maternal and perinatal results may be obtained. 

PMID- 25584036
TI  - A new biological marker candidate in female reproductive system diseases: Matrix
      metalloproteinase with thrombospondin motifs (ADAMTS).
AB  - Playing a key role in the pathophysiology of many diseases, A Disintegrin-like
      and Metalloproteinase with Thrombospondin type-1 motif (ADAMTS) proteinases have
      been attracted more attention in obstetrics and gynecology. First discovered in
      1997, this zinc-dependent proteinase family has 19 members today. These enzymes,
      which are located in the extracellular matrix (ECM), have a lot of very important
      functions, like matrix formation and resorption, angiogenesis, ovulation, and
      coagulation. In addition, in the pathogenesis of cancer, inflammation, arthritis,
      and connective tissue diseases, ADAMTS proteinases have crucial roles. The
      purpose of this review is to collect previous studies about obstetrics and
      gynecology that are related to ADAMTS enzymes and discuss the subject in many
      aspects to give an idea to the investigators who are interested in the subject. 

PMID- 25584038
TI  - Bicuspid aortic valve and severe aortic stenosis in a newborn exposed to
      carbamazapine during pregnancy.
AB  - The use of antiepileptic drugs increases the risk of major congenital
      malformations during pregnancy. Here, we report an infant who had a history of in
      utero carbamazepine exposure and who was born with a cardiac malformation. The
      infant was born at 39 weeks of gestation vaginally to an epileptic mother who had
      been treated with carbamazepine throughout her pregnancy. He was referred due to
      cardiac murmur in the second week of his life. The mother had not received folic
      acid supplementation. Transthoracic echocardiography revealed bicuspid aortic
      valve, mild aortic stenosis, patent ductus arteriosus, patent foramen ovale and
      the renal ultrasound revealed mild left hydronephrosis. Follow-up
      echocardiography performed 14 weeks later showed increased severity of aortic
      stenosis and percutaneous balloon aortic valvuloplasty was performed. To our
      knowledge, there is only one case report in the literature mentioning the
      association of a bicuspid aortic valve and aortic stenosis with oxcarbazepine
      exposure, which is a structural derivative of carbamazepine. However, there are
      no reports for association with carbamazepine itself. Bicuspid aorta and aortic
      stenosis may be among the cardiac malformations that result from the teratogenic
      effect of carbamazepine. 

PMID- 25584039
TI  - What is your diagnosis?

PMID- 25584040
TI  - Maternal vitamin D supplementation and its impact on allergy.

PMID- 25584041
TI  - Neonatal treatment of CINCA syndrome.
AB  - Chronic Infantile Neurological Cutaneous Articular (CINCA) syndrome, also called
      Neonatal Onset Multisystem Inflammatory Disease (NOMID) is a chronic disease with
      early onset affecting mainly the central nervous system, bones and joints and may
      lead to permanent damage. We report two preterm infants with severe CINCA
      syndrome treated by anti-interleukin-1 in the neonatal period, although, so far,
      no experience with this treatment in infants younger than three months of age has
      been reported. A review of the literature was performed with focus on treatment
      and neonatal features of CINCA syndrome. CASE REPORT: Two cases suspected to have
      CINCA syndrome were put on treatment with anakinra in the early neonatal period
      due to severe clinical presentation. We observed a rapid and persistent decline
      of clinical signs and systemic inflammation and good drug tolerance. Diagnosis
      was confirmed in both cases by mutations in the NLRP3/CIAS1-gene coding for
      cryopyrin. As particular neonatal clinical signs polyhydramnios and endocardial
      overgrowth are to be mentioned. CONCLUSION: We strongly suggest that specific
      treatment targeting interleukin-1 activity should be started early. Being well
      tolerated, it can be introduced already in neonates presenting clinical signs of
      severe CINCA syndrome in order to rapidly control inflammation and to prevent
      life-long disability.

PMID- 25584042
TI  - Procedural pain and patient-reported side effects with weekly injections of
      subcutaneous methotrexate in children with rheumatic disorders.
AB  - BACKGROUND: Despite the widespread use of subcutaneous methotrexate in treating
      pediatric rheumatic disorders, the amount of pain associated with the injections
      has not been quantified. Our study aims 1) to quantify the amount of pain
      associated with subcutaneous injections of methotrexate, 2) to explore predictors
      of pain, 3) to determine the frequency of patient-reported clinical adverse
      effects of methotrexate, and 4) identify coping strategies of patients and
      caregivers. METHODS: Patients aged 4-17 years with rheumatologic diseases who
      were receiving weekly subcutaneous methotrexate injections for at least 4 weeks
      were invited to participate in this prospective cohort study. They were trained
      to use the Faces Pain Scale-Revised (FPS-R) and Faces, Legs, Arms, Cry,
      Consolability (FLACC) tools to rate pain associated with the injections. All
      patients underwent focused interviews exploring their experiences with
      methotrexate injections. RESULTS: Forty-one patients consented to the study. The
      mean age was 11.2 years (SD = 3.9 years) and 68% were female. Most patients were
      diagnosed with JIA (73%). Mean duration of methotrexate therapy was 2.5 years (SD
      = 2.1 yrs). All but one of the patients used methotrexate 25 mg/ml solution for
      injection in 1 cc or 3 cc syringe with 30 gauge 1/2" needle. Median amount of
      pain was 2/10 on the FPS-R and 1/10 on the FLACC. Higher intensity of pain was
      significantly associated with presence of side effects (p = 0.004), but not
      duration of therapy (p = 0.20) or age (p = 0.24). Most participants (61%)
      experienced at least one adverse effect; nausea (56%) and vomiting (34%) were the
      most common symptoms reported. Patients and caregivers reported using ice (34%),
      comfort positions (51%), rewards (49%), reassurance (54%), distraction (51%), and
      analgesic medications (22%) to cope with the injections. CONCLUSION: Subcutaneous
      injections of methotrexate are associated with a mild amount of pain. Presence of
      side effects may amplify the amount of perceived pain. Clinicians can apply this
      knowledge when counseling patients and family members about methotrexate therapy.

PMID- 25584043
TI  - REACTIVE OXYGEN SPECIES AND COLORECTAL CANCER.
AB  - Several agents used for treatment of colon and other cancers induce reactive
      oxygen species (ROS) and this plays an important role in their anticancer
      activities. In addition to the well-known proapoptotic effects of ROS inducers,
      these compounds also decrease expression of specificity protein (Sp)
      transcription factors Sp1, Sp3 and Sp4 and several pro-oncogenic Spregulated
      genes important for cancer cell proliferation, survival and metastasis. The
      mechanism of these responses involve ROS-dependent downregulation of microRNA-27a
      (miR-27a) or miR-20a (and paralogs) and induction of two Sp-repressors, ZBTB10
      and ZBTB4 respectively. This pathway significantly contributes to the anticancer
      activity of ROS inducers and should be considered in development of drug
      combinations for cancer chemotherapy.

PMID- 25584044
TI  - Human Umbilical Cord-Derived Mesenchymal Stem Cells Utilize Activin-A to Suppress
      Interferon-gamma Production by Natural Killer Cells.
AB  - Following allogeneic hematopoietic stem cell transplantation (HSCT), interferon
      (IFN)-gamma levels in the recipient's body can strongly influence the clinical
      outcome. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are
      lucrative as biological tolerance-inducers in HSCT settings. Hence, we studied
      the molecular mechanism of how UC-MSCs influence natural killer (NK) cell
      mediated IFN-gamma production. Allogeneic NK cells were cultured in direct
      contact with UC-MSCs or cell-free supernatants from mesenchymal stem cell (MSC)
      cultures (MSC-conditioned media). We found that soluble factors secreted by UC
      MSCs strongly suppressed interleukin (IL)-12/IL-18-induced IFN-gamma production
      by NK cells by reducing phosphorylation of STAT4, NF-kappaB, as well as T-bet
      activity. UC-MSCs secreted considerable amounts of activin-A, which could
      suppress IFN-gamma production by NK cells. Neutralization of activin-A in MSC
      conditioned media significantly abrogated their suppressive abilities. Till date,
      multiple groups have reported that prostaglandin (PG)-E2 produced by MSCs can
      suppress NK cell functions. Indeed, we found that inhibition of PGE2 production
      by MSCs could also significantly restore IFN-gamma production. However, the
      effects of activin-A and PGE2 were not cumulative. To the best of our knowledge,
      we are first to report the role of activin-A in MSC-mediated suppression of IFN
      gamma production by NK cells. 

PMID- 25584045
TI  - Massive attack by honeybees in a German shepherd dog: description of a fatal case
      and review of the literature.
AB  - In the present study, a fatal case caused by honeybee (Apis cerana) stings was
      documented in a female German shepherd dog that was presented at the Veterinary
      Teaching Hospital, University of Agriculture Faisalabad, Pakistan. Characteristic
      clinical signs included hematuria, hematemesis, incoordination and convulsions
      along with evidence of massive honeybee attack supported the diagnosis of
      envenomation. The dog was treated with dexamethasone and diphenhydramine, but it
      did not respond to therapy and died. This outcome could be avoided if we had a
      bee antivenom available for treating envenomated patients. 

PMID- 25584046
TI  - Congenital hyperinsulinism: clinical and molecular characterisation of compound
      heterozygous ABCC8 mutation responsive to Diazoxide therapy.
AB  - BACKGROUND: Mutations in ABCC8 and KCNJ11 are the most common cause of congenital
      hyperinsulinism (CHI). Recessive as well as dominant acting ABCC8/KCNJ11
      mutations have been described. Diazoxide, which is the first line medication for
      CHI, is usually ineffective in recessive ABCC8 mutations. We describe the
      clinical and molecular characterisation of a recessive ABCC8 mutation in a CHI
      patient that is diazoxide response. CLINICAL CASE: A term macrosomic female
      infant presented with symptomatic persistent hypoglycaemia confirmed to be
      secondary to CHI. She exhibited an excellent response to moderate doses of
      diazoxide (10 mg/kg/day). Molecular genetic analysis of the proband confirmed a
      biallelic ABCC8 mutation - missense R526C inherited from an unaffected mother and
      a frameshift c.1879delC mutation (H627Mfs*20) inherited from an unaffected
      father. Follow-up highlighted persistent requirement for diazoxide to control
      CHI. Functional analysis of mutants confirmed them to result in diazoxide
      responsive CHI, consistent with the clinical phenotype. CONCLUSION: Biallelic
      ABCC8 mutations may result in diazoxide-responsive CHI. Irrespective of the
      molecular genetic analysis results, accurate assessment of the response to
      diazoxide should be undertaken before classifying a patient as diazoxide
      responsive or unresponsive CHI.

PMID- 25584047
TI  - GPS suggests low physical activity in urban Hispanic school children: a proof of
      concept study.
AB  - BACKGROUND: Urban environments can increase risk for development of obesity,
      insulin resistance (IR), and type 2 diabetes mellitus (T2DM) by limiting physical
      activity. This study examined, in a cohort of urban Hispanic youth, the
      relationship between daily physical activity (PA) measured by GPS, insulin
      resistance and cardiovascular fitness. METHODS: Hispanic middle school children
      (n = 141) were assessed for body mass index (BMI), IR (homeostasis model [HOMA
      IR]), cardiovascular fitness (progressive aerobic cardiovascular endurance run
      [PACER]). PA was measured (GPS-PA) and energy expenditure estimated (GPS-EE)
      utilizing a global positioning mapping device worn for up to 7 days. RESULTS:
      Students (mean age 12.7 +/- 1.2 years, 52% female) spent 98% of waking time in
      sedentary activities, 1.7% in moderate intensity PA, and 0.3% in vigorous
      intensity. GPS analysis revealed extremely low amounts of physical movement
      during waking hours. The degree of low PA confounded correlation analysis with
      PACER or HOMA-IR. CONCLUSIONS: Levels of moderate and vigorous intensity PA,
      measured by GPS, were extremely low in these urban Hispanic youth, possibly
      contributing to high rates of obesity and IR. Physical movement patterns suggest
      barriers to PA in play options near home, transportation to school, and in school
      recess time. GPS technology can objectively and accurately evaluate initiatives
      designed to reduce obesity and its morbidities by increasing PA.

PMID- 25584048
TI  - Comparison of various concentrations of tricalcium phosphate nanoparticles on
      mechanical properties and remineralization of fissure sealants.
AB  - OBJECTIVE: The aim of this study was to investigate the mechanical properties
      (flexural strength, micro-shear bond strength) and remineralizing potential of
      fissure sealants by adding various concentrations of beta-tricalcium phosphate
      nanoparticles. MATERIALS AND METHODS: This in-vitro study consisted of five
      experimental groups containing prepared nano-fisssure sealants (1-5 wt.% beta-TCP
      nanoparticles) and two control groups containing a prepared and a commercial
      fissure sealant. Flexural/micro-shear bond strength values were measured using
      Zwick test machine. Cavities on sixty healthy premolar teeth were filled with the
      fissure sealants containing 0-5 wt.% of nano beta-TCP. The samples were assessed
      for remineralization under scanning electron microscopy (SEM) and EDAX.
      Kolmogorov-Smirnov test, One-way ANOVA and Tukey's Post Hoc analysis/HSD were
      used to analyze the data. RESULTS: There was no significant difference between
      the flexural strengths/elastic modulus of the 0-5 wt.% nano beta-TCP groups
      (p>0.05). The average flexural strength/elastic modulus of the prepared fissure
      sealant group (0%) was significantly higher than the commercial fissure sealant
      group (Clinpro) (p<0.05). There was no significant difference between micro-shear
      bond strengths of the experimental groups (1-5 wt.%), and between the commercial
      and the prepared (0%) fissure sealant groups (p>0.05). Examining the samples
      under SEM showed a significant increase in thickness of the intermediate layer
      with increasing concentrations of beta-TCP nanoparticles (p<0.05). CONCLUSION:
      Addition of 1-5 wt.% beta-TCP nanoparticles to the fissure sealants significantly
      increased the remineralization potential without affecting the mechanical
      properties.

PMID- 25584049
TI  - Effects of two soft drinks on shear bond strength and adhesive remnant index of
      orthodontic metal brackets.
AB  - OBJECTIVE: Bond failure of brackets during orthodontic treatment is a common
      problem; which results in treatment interference, increased treatment time and
      prolonged clinical time for rebonding of failed brackets. The purpose of this
      study was to evaluate the effects of Coca-Cola and a non-alcoholic beer on the
      shear bond strength and adhesive remnant index (ARI) of orthodontic metal
      brackets in vitro. MATERIALS AND METHODS: Eighty intact human premolars were
      divided into two experimental groups of Coca-Cola and non-alcoholic beer (Istak),
      and a control group of artificial saliva. Over a period of thirty days, the test
      groups were immersed in the respective soft drinks for 5 minutes, twice a day.
      For the remainder of the time, they were kept in artificial saliva at 37 degrees
      C. The control group was stored in artificial saliva during the experiment. All
      samples were subjected to shearing forces using Universal Testing Machine. ARI
      was determined with a stereomicroscope at *12 magnification. The data of shear
      bond strength were statistically analyzed by one-way ANOVA and Tukey's Post-Hoc
      test and the data of ARI scores were analyzed by Kruskal-Wallis test. RESULTS: No
      significant difference was observed in ARIs of the three groups (P<= 0.552). The
      shear bond strength of Coke group was significantly lower than that of the two
      other groups (P<= 0.035); but there was no significant difference between the
      shear bond strength of Istak and the control group (P<= 0.999). CONCLUSION: Coca
      Cola decreased the shear bond strength of orthodontic brackets.

PMID- 25584051
TI  - Comparison of nano-hydroxyapatite and sodium fluoride mouthrinse for
      remineralization of incipient carious lesions.
AB  - OBJECTIVE: Dental caries is an infectious disease that can be prevented in
      several ways. The aim of this study was to compare the efficacy of sodium
      fluoride mouthrinse and nano- hydroxyapatite (nano-HA) for the remineralization
      of incipient caries. MATERIALS AND METHODS: After obtaining different
      concentrations of nano-HA (0-2-5-10%), 60 sound premolars fixed in acrylic blocks
      were coated with nail polish except for one surface. Ten teeth (control group)
      were stored in distilled water and the remaining 50 samples were demineralized by
      immersion in 13 ml of 0.1 M lactic acid and 0.2% poly acrylic acid for 48 hours.
      Their microhardness was then measured and compared to that of the control group.
      Next, the 50 test teeth were randomly divided into 5 groups of group1 (negative),
      group 2 (2% nano-HA), group 3 (5% nano-HA), group 4(10% nano-HA) and group 5 (0.2
      NAF mouthrinse). The microhardness of the teeth was measured after 12 hours of
      immersion in the above-mentioned solutions. Data were analyzed using repeated
      measures analysis of variance (ANOVA). RESULTS: Microhardness of all samples
      decreased significantly after immersion in the demineralization solution and
      increased following immersion in nano-HA and NAF mouthrinses; however, this
      increase was not statistically significant (P=0.711). CONCLUSION: Nano-HA and NAF
      mouthrinses can greatly enhance remineralization and increase tooth
      microhardness.

PMID- 25584050
TI  - Dimensional changes of acrylic resin denture bases: conventional versus injection
      molding technique.
AB  - OBJECTIVE: Acrylic resin denture bases undergo dimensional changes during
      polymerization. Injection molding techniques are reported to reduce these changes
      and thereby improve physical properties of denture bases. The aim of this study
      was to compare dimensional changes of specimens processed by conventional and
      injection-molding techniques. MATERIALS AND METHODS: SR-Ivocap Triplex Hot resin
      was used for conventional pressure-packed and SR-Ivocap High Impact was used for
      injection-molding techniques. After processing, all the specimens were stored in
      distilled water at room temperature until measured. For dimensional accuracy
      evaluation, measurements were recorded at 24-hour, 48-hour and 12-day intervals
      using a digital caliper with an accuracy of 0.01 mm. Statistical analysis was
      carried out by SPSS (SPSS Inc., Chicago, IL, USA) using t-test and repeated
      measures ANOVA. Statistical significance was defined at P<0.05. RESULTS: After
      each water storage period, the acrylic specimens produced by injection exhibited
      less dimensional changes compared to those produced by the conventional
      technique. Curing shrinkage was compensated by water sorption with an increase in
      water storage time decreasing dimensional changes. CONCLUSION: Within the
      limitations of this study, dimensional changes of acrylic resin specimens were
      influenced by the molding technique used and SR-Ivocap injection procedure
      exhibited higher dimensional accuracy compared to conventional molding.

PMID- 25584052
TI  - Effect of Argon Laser on Enamel Demineralization around Orthodontic Brackets: An
      In Vitro Study.
AB  - OBJECTIVE: This study was designed to evaluate the effect of argon laser
      irradiation on development and progress of enamel demineralization around
      orthodontic brackets. MATERIALS AND METHODS: Fifty caries-free, intact human
      premolars were randomly assigned to one of the following five equal groups:
      Groups 1 (control) and 2: The brackets were bonded using conventional halogen
      light for 40s and argon laser for 10s, respectively. Teeth in group 3 were lased
      with argon laser for 10s before bracket bonding with halogen light. Group 4 was
      the same as group 3 except that brackets were also bonded with argon laser. In
      group 5 samples were bonded conventionally, immersed in an artificial caries
      solution for two days and then irradiated for 10s with argon laser. All samples
      were subjected to demineralization by artificial caries solution for 10 days.
      After bracket removal, samples were buccolingually sectioned and evaluated by
      polarized light microscopy. Decalcified lesion depth in each section was measured
      by a trained examiner in a blind fashion. Data were analyzed in SPSS 14 using one
      way ANOVA and Tukey's HSD post hoc test. RESULTS: The control group showed the
      greatest mean lesion depth while group 5 revealed the lowest. The laser-treated
      groups had significantly lower mean lesion depth compared with the control group
      (P<0.05) except for group 4 (P=0.192). CONCLUSION: Argon laser irradiation for
      10s before or during bracket bonding can increase caries resistance of intact and
      demineralized enamel.

PMID- 25584053
TI  - Microleakage of two self-adhesive cements in the enamel and dentin after 24 hours
      and two months.
AB  - OBJECTIVE: Microleakage is a main cause of restorative treatment failure. In this
      study, we compared occlusal and cervical microleakage of two self-adhesive
      cements after 24 hours and two months. MATERIALS AND METHODS: In this in-vitro
      experimental study, class II inlay cavities were prepared on 60 sound human third
      molars. Composite inlays were fabricated with Z100 composite resin. The teeth
      were randomly assigned to six groups. RelyX-Arc (control), RelyX-Unicem and
      Maxcem were used for the first three groups and specimens were stored in
      distilled water at 37 degrees C for 24 hours. The same cements were used for the
      remaining three groups, but the specimens were stored for 2 months. The teeth
      were subjected to 500 thermal cycles (5 degrees C and 55 degrees C) and immersed
      in 0.5% basic fuchsin for 24 hours and then sectioned mesiodistally and dye
      penetration was evaluated in a class II cavity with occlusal and cervical margins
      using X20 magnification stereomicroscope. Data were analyzed using Kruskal Wallis
      and Mann-Whitney U tests. RESULTS: After 24 hours, cements had significant
      differences only in cervical margin microleakage (P=0.0001) and microleakage of
      RelyX-Unicem and Maxcem was significantly more than that of RelyX-Arc (both
      P=0.0001). Cervical microleakage in RelyX-Unicem and Maxcem was greater than
      occlusal (P=0.0001 and P=0.001, respectively). Microleakage was not significantly
      different between the occlusal and cervical margins after 2 months. CONCLUSION:
      Cervical microleakage was greater than occlusal in RelyX-Unicem and Maxcem after
      24h. The greatest microleakage was reported for the cervical margin of RelyX
      Unicem after 24 hours.

PMID- 25584054
TI  - Enamel thickness after preparation of tooth for porcelain laminate.
AB  - OBJECTIVE: In this investigation the thickness of enamel in the gingival, middle,
      and incisal thirds of the labial surface of the anterior teeth were measured
      regarding preparation of the teeth for porcelain laminate veneers. MATERIALS AND
      METHODS: Part one, 20 extracted intact human maxillary central and lateral
      incisors ten of each were selected. The teeth were imbedded in autopolimerize
      acrylic resin. Cross section was preformed through the midline of the incisal,
      middle and cervical one-third of the labial surface of the teeth. The samples
      were observed under reflected stereomicroscope and the thickness of enamel was
      recorded. Part II, the effect of different types of preparation on dentin
      exposure was evaluated. Thirty maxillary central incisor teeth were randomly
      divided into two groups: A: Knife-edge preparation. B: Chamfer preparation. All
      samples were embedded in autopolimerize acrylic resin using a silicon mold. The
      samples were cut through the midline of the teeth. The surface of the samples
      were polished and enamel and dentin were observed under the stereomicroscope.
      RESULTS: Data were analyzed by ANOVA-one way test. The results of this study
      showed that the least enamel thickness in the central incisor was 345 and in
      lateral incisor is 235 MU this thickness is related to the one-third labial
      cervical area. Maximum thickness in maxillary central and lateral incisors in the
      one-third labial incisal surface was 1260 MU and 1220MU, respectively. In the
      second part of the study, the tendency of dentinal exposure was shown with the
      chamfer preparation, but no dentinal exposure was found in the knife-edge
      preparation. The differences between groups were significant (p<0.05).
      CONCLUSION: The knowledge of enamel thickness in different part of labial surface
      is very important. The thickness of enamel in the gingival area does not permit a
      chamfer preparation. The knife edge preparation is preferable in gingival area.

PMID- 25584055
TI  - Apical Extrusion of Irrigants in Immature Permanent Teeth by Using EndoVac and
      Needle Irrigation: An In Vitro Study.
AB  - OBJECTIVE: Immature teeth have a large apical opening and thin divergent or
      parallel dentinal walls; hence, with conventional needle irrigation there is a
      very high possibility of extrusion. This study was done to compare the apical
      extrusion of NaOCl in an immature root delivered using EndoVac and needle
      irrigation. MATERIALS AND METHODS: Eighty freshly extracted maxillary central
      incisors were decoronated followed by access cavity preparation. Modified
      organotypic protocol was performed to create an open apex; then, the samples were
      divided into four groups (n=20): EndoVac Microcannula (group I), EndoVac
      Macrocannula (group II), NaviTip irrigation needle (group III) and Max-i-Probe
      Irrigating needle (group IV); 9.0 ml of 3% sodium hypochlorite was delivered
      slowly over a period of 60 seconds. Extruded irrigants were collected in a vial
      and analysed statistically. RESULTS: Group I, group III and group IV showed 100%
      extrusion (20/20) but group II showed only 40% extrusion (8/20). The difference
      in this respect between group II and other groups was statistically significant
      (P<0.001). With regards to the volume of extrusion, group II had only 0.23 ml of
      extruded irrigant. Group I extruded 7.53ml of the irrigant. Group III and group
      IV extruded the entire volume of irrigant delivered. CONCLUSION: EndoVac
      Macrocannula resulted in the least extrusion of irrigant in immature teeth when
      compared to EndoVac Microcannula and conventional needle irrigation.

PMID- 25584056
TI  - Cone-beam Computed Tomographic Assessment of Canal Centering Ability and
      Transportation after Preparation with Twisted File and Bio RaCe Instrumentation.
AB  - OBJECTIVE: Use of rotary Nickel-Titanium (NiTi) instruments for endodontic
      preparation has introduced a new era in endodontic practice, but this issue has
      undergone dramatic modifications in order to achieve improved shaping abilities.
      Cone-beam computed tomography (CBCT) has made it possible to accurately evaluate
      geometrical changes following canal preparation. This study was carried out to
      compare canal centering ability and transportation of Twisted File and BioRaCe
      rotary systems by means of cone-beam computed tomography. MATERIALS AND METHODS:
      Thirty root canals from freshly extracted mandibular and maxillary teeth were
      selected. Teeth were mounted and scanned before and after preparation by CBCT at
      different apical levels. Specimens were divided into 2 groups of 15. In the first
      group Twisted File and in the second, BioRaCe was used for canal preparation.
      Canal transportation and centering ability after preparation were assessed by NNT
      Viewer and Photoshop CS4 software. Statistical analysis was performed using t
      test and two-way ANOVA. RESULTS: All samples showed deviations from the original
      axes of the canals. No significant differences were detected between the two
      rotary NiTi instruments for canal centering ability in all sections. Regarding
      canal transportation however, a significant difference was seen in the BioRaCe
      group at 7.5mm from the apex. CONCLUSION: Under the conditions of this in vitro
      study, Twisted File and BioRaCe rotary NiTi files retained original canal
      geometry.

PMID- 25584057
TI  - Effect of root resection on sealing ability of orthograde apical plugs of mineral
      trioxide aggregate and calcium enriched mixture.
AB  - OBJECTIVE: There is some concern that root resection may alter the seal of the
      previously set orthograde material. The aim of this study was to evaluate the
      apical sealing ability of orthograde mineral trioxide aggregate (MTA) and calcium
      enriched mixture (CEM) plugs after resection of the roots. MATERIALS AND METHODS:
      The fluid filtration method was carried out on a total of 51 roots in three
      experimental (n=15) and two control (n=3) groups. The root canals were prepared 3
      mm shorter than the working length. In groups A and B, 4 mm of MTA and CEM were
      placed in an orthograde technique, respectively, and after setting, 3 mm of the
      root end was resected. In group C, the apical 3 mm of each root was resected,
      root end preparation was carried out to a depth of 3 mm and filled with MTA.
      Apical microleakage values of each group were measured. Data was analyzed using
      Kruskal-Wallis test. RESULTS: Means and standard deviations of apical
      microleakage in groups A (MTA orthograde), B (CEM orthograde) and C (MTA
      retrograde) were 2.31*10(-4) (0.32*10(-4)), 3.33*10(-4) (0.29*10(-4)) and
      4.42*10(-4) (0.40*10(-4)) MUl.min(-1).cmH2o(-1), respectively. The mean values
      were greater in group C; however, statistical analysis revealed no significant
      differences between these groups (P>0.05). CONCLUSION: Based on the results of
      this study, when there is an orthograde access to the root canal and surgery is
      likely to be necessary in the future, MTA and CEM can be placed in an orthograde
      technique and it just resects the root during surgery.

PMID- 25584058
TI  - Effect of the type of endodontic sealer on the bond strength between fiber post
      and root wall dentin.
AB  - OBJECTIVES: An important factor that interferes with the bonding between the root
      canal wall and resin cement is the root canal sealer remnant. There is
      controversy about the effect of eugenol-containing sealers on the bond strength
      between resin cements and fiber post. The aim of this study was to evaluate the
      effect of the type of endodontic sealer on the bond strength of FRC posts
      cemented with resin cement to the root canal wall. MATERIALS AND METHODS: In this
      in vitro study, 20 extracted mandibular first premolars were endodontically
      treated and divided into two groups according to the endodontic sealer used
      (n=10): G1: AH26 (Resin based); and G2: Endofill (Eugenol-based). After preparing
      post space, adhesive resin cement (Panavia F 2.0) was used for cementation of the
      fiber post to the root canal dentin. Three 3 mm thick slices were obtained from
      each root. The push-out test was performed with a cross-head speed of 1
      mm/minute. Two-way ANOVA and Tukey post hoc tests were used for analyzing data
      (alpha=0.05). RESULTS: The two-way ANOVA showed that different root canal sealers
      (P=0.037) had significant effects on bond strength (BS), but root canal regions
      (P=0.811) and interaction between root canal sealers and root canal regions
      (P=0.258) had no significant effects on BS. Maximum and minimum mean values were
      observed in the AH26 group, the apical region and the Endofill group in the
      apical region, respectively. Post Hoc Tukey test revealed that there were no
      significant differences between different root canal regions in both cements
      (P>0.05). CONCLUSION: The region of root canal had no effect on the bond strength
      of cemented fiber posts to the root canal. Eugenol-based sealers (Endofill)
      significantly reduced the bond strength between fiber posts luted with resin
      cement to the root canal.

PMID- 25584059
TI  - Antibacterial effect of an herbal product persica on porphyromonas gingivalis and
      aggregatibacter actinomycetemcomitans: an in-vitro study.
AB  - OBJECTIVE: The plant Salvadora persica is used for oral hygiene in many parts of
      the world. It has been suggested that it has antibacterial properties, in
      addition to its ability to mechanically remove plaques. The aim of this study was
      to assess the antimicrobial activity of the herbal product Persica containing
      Salvadora persica against periodontopathogens Porphyromonas gingivalis and
      Aggregatibacter actinomycetemcomitans in vitro. MATERIALS AND METHODS: Fifty
      patients with moderate and severe periodontitis were recruited. Using paper
      points, subgingival plaque samples were taken from pockets with attachment loss
      >= 3mm. The samples were subjected to microbial culture to yield P. gingivalis
      and A. actinomycetemcomitans. The ditch plate method was used for antimicrobial
      susceptibility testing of the bacteria to Persica compared to chlorhexidine and
      distilled water. The growth inhibition zones of microorganisms around the ditches
      were measured in millimeters. The data were analyzed using SPSS 16. Freidman test
      and Wilcoxon signed ranks test with Bonferroni adjustment were used for analysis
      of variance with 5% significance level. P<0.05 for main comparisons and P< 0.017
      for multiple comparisons were considered statistically significant. RESULTS: P.
      gingivalis was sensitive to chlorhexidine and persica. There was a significant
      difference (P=0.001) between antimicrobial activity of chlorhexidine (mean
      28.733mm, SD 5.216) and Persica (mean 16.333mm, SD 5.259) compared to water
      against P. gingivalis. There was a significant difference (P< 0.001) between the
      antimicrobial activity of chlorhexidine (24.045mm, SD 3.897) and Persica
      (0.545mm, SD 2.558) with respect to A. actinomycetemcomitans. There was no
      significant difference (P=0.317) between the antimicrobial activity of Persica
      and water against A. actinomycetemcomitans. CONCLUSION: The herbal product
      Persica had significant antimicrobial activity against P. gingivalis and
      negligible antimicrobial activity against A. actinomycetemcomitans compared to
      0.2% chlorhexidine.

PMID- 25584060
TI  - In vitro evaluation of veneering composites and fibers on the color of fiber
      reinforced composite restorations.
AB  - OBJECTIVE: Color match between fiber-reinforced composite (FRC) restorations and
      teeth is an imperative factor in esthetic dentistry. The purpose of this study is
      to evaluate the influence of veneering composites and fibers on the color change
      of FRC restorations. MATERIALS AND METHODS: Glass and polyethylene fibers were
      used to reinforce a direct microhybrid composite (Z250, 3M ESPE) and a
      microfilled composite (Gradia Indirect, GC). There were eight experimental groups
      (n=5 disks per group). Four groups were used as the controls (non-FRC control)
      and the others were used as experimental groups. CIELAB parameters (L*, a* and
      b*) of specimens were evaluated against a white background using a
      spectrophotometer to assess the color change. The color difference (DeltaE*) and
      color coordinates were (L*, a* and b*) analyzed by two-way ANOVA and Tukey's
      test. RESULTS: Both types of composite and fiber influenced the color parameters
      (DeltaL*, Deltaa*). The incorporation of fibers into the composite in the
      experimental groups made them darker than the control groups, except in the
      Gradia Indirect+ glass fibers group. Deltab* is affected by types of fibers only
      in direct fiber reinforced composite. No statistically significant differences
      were recognized in DeltaE* among the groups (p>0.05). CONCLUSION: The findings of
      the present study suggest that the tested FRC restorations exhibited no
      difference in color in comparison with non-FRC restoration. Hence, the types of
      veneering composites and fibers did not influence the color change (DeltaE*) of
      FRC restorations.

PMID- 25584061
TI  - Labial ankyloglossia associated with oligodontia: a case report.
AB  - Developmental disturbances of the tongue (aglossia, macroglossia, microglossia,
      and ankyloglossia) can adversely affect the development of the surrounding
      structures including the palate, alveolar process, and teeth. These developmental
      disturbances impair functions such as mastication, speech, and swallowing.
      Ankyloglossia is of various types and may be associated with other syndromic
      features like cleft palate. We report a rare type of non-syndromic ankyloglossia
      associated with missing of the permanent anterior tooth. 

PMID- 25584062
TI  - Co-existence of two dens invaginations with one dens evagination in a maxillary
      lateral incisor: a case report.
AB  - A case with two simultaneous dens invaginations (DIs) and one dens evagination
      (DE) in a permanent maxillary lateral incisor is reported for the first time in a
      21-year-old girl. DE known as talon cusp of the anterior teeth is a rare entity
      and its co-existence with DI has been reported scarcely in the literature.
      Simultaneous occurrence of two DIs with one DE has not been reported elsewhere.
      Undoubtedly, familiarity with the internal anatomy of such a rare condition can
      help prevent pulpal disease while performing restorative procedures. 

PMID- 25584063
TI  - Endodontic management of three-canalled mandibular lateral incisor using dental
      operating microscope.
AB  - This case report presents endodontic management of a mandibular lateral incisor
      with three canals using surgical dental operating microscope. This study
      describes the root canal variation of mandibular lateral incisor and highlights
      the importance of surgical operating microscope in detecting an unusual canal
      morphology. 

PMID- 25584064
TI  - Geriatric trauma hip fractures: is there a difference in outcomes based on
      fracture patterns?
AB  - BACKGROUND: Annually in the US, there are over 300,000 hospital admissions due to
      hip fractures in geriatric patients. Consequently, there have been several large
      observational studies, which continue to provide new insights into differences in
      outcomes among hip fracture patients. However, few hip fracture studies have
      specifically examined the relationship between hip fracture patterns, sex, and
      short-term outcomes including hospital length of stay and discharge disposition
      in geriatric trauma patients. METHODS: We performed a retrospective study of hip
      fractures in geriatric trauma patients. Hip fracture patterns were based on ICD 
      9 CM diagnostic codes for hip fractures (820.00-820.9). Patient variables were
      patient demographics, mechanism of injury, injury severity score, hospital and
      ICU length of stay, co-morbidities, injury location, discharge disposition, and
      in-patient mortality. RESULTS: A total of 325 patient records met the inclusion
      criteria. The mean age of the patients was 82.2 years, and the majority of the
      patients were white (94%) and female (70%). Hip fractures patterns were
      categorized as two fracture classes and three fracture types. We observed a
      difference in the proportion of males to females within each fracture class
      (Femoral neck fractures Z-score = -8.86, p < 0.001, trochanteric fractures Z
      score = -5.63, p < 0.001). Hip fractures were fixed based on fracture pattern and
      patient characteristics. Hip fracture class or fracture type did not predict
      short-term outcomes such as in-hospital or ICU length of stay, death, or patient
      discharge disposition. The majority of patients (73%) were injured at home.
      However, 84% of the patients were discharged to skilled nursing facility,
      rehabilitation, or long-term care while only 16% were discharged home. There was
      no evidence of significant association between fracture pattern, injury severity
      score, diabetes mellitus, hypertension or dementia. CONCLUSIONS: Hip fracture
      patterns differ between geriatric male and female trauma patients. However, there
      was no significant association between fracture patterns and short-term patient
      outcomes. Further studies are planned to investigate the effect of fracture
      pattern and long-term outcomes including 90-day mortality, return to previous
      levels of activity, and other quality of life measures.

PMID- 25584065
TI  - Toothpick ingestion complicated by cecal perforation: case report and literature
      review.
AB  - BACKGROUND: Diverticulitis and carcinoma represent the most common causes of
      colon perforation, but other causes, like ingestion of foreign bodies, should be
      taken into account. CASE PRESENTATION: We report the case of a 64-year old man
      presenting in our Emergency Department with a 2 days history of right lower
      abdominal pain, nausea, vomiting and low grade fever. Physical examination
      evocated mild pain with positive rebound tenderness in the right lower abdominal
      quadrant, and positive right costovertebral angle tenderness. Routine blood
      tests, abdominal X-rays and CT scan were inconclusive for perforation. At
      explorative laparoscopy a cecal perforation with localized peritonitis was found,
      and a right colectomy was performed due to the suspicion of cancer. Histological
      examination confirmed the presence of a perforation caused by a piece of wood
      (toothpick) of 6 cm in length. CONCLUSIONS: Foreign body ingestion should be
      taken into account in the evaluation of acute abdominal pain. A detailed
      patient's history may be crucial for a correct diagnosis and treatment.

PMID- 25584066
TI  - Inhibitory effect of piperine on Helicobacter pylori growth and adhesion to
      gastric adenocarcinoma cells.
AB  - BACKGROUND: Piperine is a compound comprising 5-9% of black pepper (Piper
      nigrum), which has a variety of biological roles related to anticancer
      activities. Helicobacter pylori has been classified as a gastric carcinogen,
      because it causes gastritis and gastric cancer by injecting the virulent toxin
      CagA and translocating VacA. The present study investigated the inhibitory action
      of piperine on H. pylori growth and adhesion. METHODS: Inhibition of H. pylori
      growth was determined by the broth macrodilution method, and adhesion to gastric
      adenocarcinoma cells validated by urease assay. Motility test was performed by
      motility agar and the expression of adhesion gene and flagellar gene in response
      to the piperine treatment was assessed by RT-PCR and immunoblotting. RESULTS:
      Administrated piperine suppressed the level of H. pylori adhesion to gastric
      adenocarcinoma cells in a dose dependent manner and the inhibition was
      statistically significant as determined by Student's t-test. In addition,
      piperine treatment effects on the flagellar hook gene flgE and integral membrane
      component of the export apparatus gene flhA expression to be suppressed and
      piperine diminished the H. pylori motility. CONCLUSIONS: flhA, encodes an
      integral membrane component of the export apparatus, which is also one of the
      regulatory protein in the class 2 genes expression and flgE is one of them that
      encodes hook part of the flagella. Suppression of both genes, leads to less
      motility results in the organism attracted less towards to the gastric epithelial
      cells might be the possible reason in the adhesion inhibition. To our knowledge,
      this is the first report published on the inhibitory effects of piperine against
      the adhesion of H. pylori to gastric adenocarcinoma cells.

PMID- 25584067
TI  - Difference in suicide methods used between suicide attempters and suicide
      completers.
AB  - BACKGROUND: In light of the increased suicide rate in Korea, it has become
      important for researchers to examine the various factors associated with it. The
      purpose of this study is to compare and analyze the difference between suicide
      attempters and completers in terms of the suicide methods used and the lethality
      of these methods. In addition, we investigated certain demographic factors that
      are associated with the choice of suicide method by evaluating their lethality.
      FINDING: The most frequently used methods of suicide were different in the two
      groups of attempters and completers. Drug poisoning was the most frequent method
      in suicide attempters, whereas hanging was the most common method among suicide
      completers. Drug poisoning, stabbing, and other chemical poisoning were evaluated
      as relatively non-lethal compared to other suicide methods. While about 70.0% of
      the suicide attempters used relatively non-lethal methods, almost all suicide
      completers used lethal methods, based on our classification of the lethality of
      the method. In terms of gender, males used more lethal methods of suicide.
      CONCLUSIONS: Suicide completers' choice of suicide methods are different from
      those of suicide attempters and tend to be more lethal. Interventions to restrict
      access to more lethal suicidal methods could be a useful strategy to reduce the
      suicide rates in South Korea.

PMID- 25584068
TI  - Using the properties of soil to speed up the start-up process, enhance process
      stability, and improve the methane content and yield of solid-state anaerobic
      digestion of alkaline-pretreated poplar processing residues.
AB  - BACKGROUND: Solid-state anaerobic digestion (SS-AD) was initially adopted for the
      treatment of municipal solid waste. Recently, SS-AD has been increasingly applied
      to treat lignocellulosic biomass, such as agricultural and forestry residues.
      However, studies on the SS-AD process are few. In this study, the process
      performance and methane yield from SS-AD of alkaline-pretreated poplar processing
      residues (PPRs) were investigated using the properties of soil, such as buffering
      capacity and nutritional requirements. RESULTS: The results showed that the
      lignocellulosic structures of the poplar sample were effectively changed by NaOH
      pretreatment, as indicated by scanning electron microscopy and Fourier transform
      infrared spectra analysis. The start-up was markedly hastened, and the process
      stability was enhanced. After NaOH pretreatment, the maximum methane yield (96.1
      L/kg volatile solids (VS)) was obtained under a poplar processing residues-to
      soil sample (P-to-S) ratio of 2.5:1, which was 29.9% and 36.1% higher than that
      of PPRs (74.0 L/kg VS) and that of experiments without NaOH pretreatment (70.6
      L/kg VS), respectively. During steady state, the increase in the methane content
      of the experiment with a P-to-S ratio of 2.5:1 was 4.4 to 50.9% higher than that
      of the PPRs. Degradation of total solids and volatile solids ranged from 19.3 to
      33.0% and from 34.9 to 45.9%, respectively. The maximum reductions of cellulose
      and hemicellulose were 52.6% and 42.9%, respectively, which were in accordance
      with the maximal methane yield. T 80 for the maximum methane yield for the
      experiments with NaOH pretreatment was 11.1% shorter than that for the PPRs.
      CONCLUSIONS: Pretreatment with NaOH and addition of soil led to a significant
      improvement in the process performance and the methane yield of SS-AD of PPRs.
      The changes in lignocellulosic structures induced by NaOH pretreatment led to an
      increase in methane yield. For the purpose of practical applications, SS-AD with
      soil addition is a convenient, economical, and practical technique.

PMID- 25584069
TI  - Towards the implementation of 'no evidence of disease activity' in multiple
      sclerosis treatment: the multiple sclerosis decision model.
AB  - OBJECTIVE: The introduction of new and potent therapies for the treatment of
      relapsing remitting multiple sclerosis (MS) has increased the desire for
      therapeutic success. There is growing doubt that the mere reduction of relapse
      rate, Expanded Disability Status Scale (EDSS) progression and magnetic resonance
      imaging (MRI) markers are exclusive and appropriate factors to monitor the new
      aim of 'no evidence of disease activity' (NEDA). However, there is no generally
      accepted definition so far. METHODS: To achieve the therapeutic aim of NEDA, a
      panel of MS experts searched the available literature on clinical and
      paraclinical outcomes to propose a test battery that is sensitive to detect
      disease activity in an everyday clinical setting. RESULTS: The panel proposed to
      include, besides relapse rate, disability progression and MRI, neuropsychological
      outcome measures such as cognitive status, fatigue, depression and quality of
      life. To standardize the examinations in an economic and schematic way, a
      multifactorial model [multiple sclerosis decision model (MSDM)] that includes the
      domains 'relapse', 'disability progression', 'MRI', and 'neuropsychology' is
      proposed. The scheme reflects the complexity of the disease even in the early
      stages when scales such as the EDSS are not able to distinguish low levels of
      progression. CONCLUSION: The MSDM aims to support early treatment decisions and
      uncover timely treatment failure. Prospective investigations are required to
      prove that such a disease-monitoring concept leads to an early and effective
      silencing of disease activity.

PMID- 25584070
TI  - Switch from intravenous to subcutaneous immunoglobulin in CIDP and MMN: improved
      tolerability and patient satisfaction.
AB  - OBJECTIVES: To assess clinical outcomes and patient satisfaction in patients with
      chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or multifocal
      motor neuropathy (MMN) who were switched from intravenous immunoglobulin (IVIG)
      to subcutaneous immunoglobulin (SCIG). METHODS: Eight consecutive patients, four
      with MMN and four with CIDP, already on long-term, hospital-based IVIG were
      switched to home-based SCIG. These patients were selected on the basis of their
      requirement for relatively low treatment doses, problems experienced with IVIG,
      and their willingness to switch to SCIG. RESULTS: After a mean 33 [standard
      deviation (SD) 19] months receiving SCIG, 7 patients remained neurologically
      stable and 6 remained on a similar mean weekly immunoglobulin dose relative to
      their original intravenous dose. A good outcome was reported by 7 of the 8
      patients: there were improvements in nausea and headache (n = 4), need to travel
      to hospital (n = 4), venous access problems (n = 3), immunoglobulin-induced
      neutropenia (n = 3), treatment wearing-off fluctuations (n = 2), IVIG-induced
      allergy requiring antihistamine/hydrocortisone (n = 1) and time taken off work (n
      = 1). The eighth patient required increasing doses of immunoglobulin to maintain
      strength but still wanted to continue SCIG. Seven patients completed a
      questionnaire: there was a very high overall satisfaction level with
      immunoglobulin treatment [mean 96 (SD 5), visual analogue scale (VAS) where 0 =
      very unsatisfied, 100 = very satisfied]; and very strong preference for
      subcutaneous over intravenous immunoglobulin (VAS mean 93 [SD 12] where 0 =
      prefer IVIG, 100 = prefer SCIG). CONCLUSIONS: In seven of the eight patients,
      SCIG gave improved tolerability and patient satisfaction with similar efficacy
      compared with IVIG.

PMID- 25584071
TI  - Dimethyl fumarate in the treatment of relapsing-remitting multiple sclerosis: an
      overview.
AB  - Multiple sclerosis (MS) shares an immune-mediated origin with psoriasis. Long
      term safety and efficacy data generated in Europe from usage of fumaric acid
      formulations in the latter disease constituted grounds to investigate their
      effects in MS patients. Dimethyl fumarate (DMF) was found to be the active
      principle in those formulations and in vitro studies have demonstrated that DMF
      has immune-modulatory properties exerted through abilities to divert cytokine
      production toward a Th2 profile, both on lymphocytes and microglial cells. More
      importantly, DMF was discovered to impact the anti-oxidative stress cell
      machinery promoting the transcription of genes downstream to the activation of
      the nuclear factor (erythroid derived 2)-like2 (NRF2). DMF exposure increases the
      cytosol concentrations of NRF2, which besides immune regulatory effects, has the
      potential for cytoprotection on glial cells, oligodendrocytes and neurons.
      Extensive and rigorous clinical trials have assessed the efficacy and safety of
      DMF at the dose of 240 mg twice and three times a day in relapsing-remitting MS
      patients during one phase IIb and two phase III trials. Robust, positive results
      were obtained across a number of clinical and paraclinical parameters. In one
      study (DEFINE), the relative reductions of the adjusted annualized relapse rate
      of the low and high dose regimens in comparison with placebo were 53% and 48%,
      respectively (p < 0.001 for both comparisons). In the other trial (CONFIRM), DMF
      decreased the annualized relapse rate in comparison with placebo by 44% in the
      lower and by 51% in higher dosage group (also p < 0.001). The number and size of
      lesions as detected by magnetic resonance imaging were also significantly
      decreased in comparison with the patients receiving DMF at every dosage. Multiple
      post hoc and subgroup analyses corroborated the clinical data, rendering DMF an
      appealing medication whose potential for impacting the degenerative aspects of MS
      remains to be explored. 

PMID- 25584072
TI  - Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results
      and considerations for use.
AB  - Alemtuzumab is a humanized monoclonal antibody therapy that has recently been
      approved in over 30 countries for patients with active relapsing-remitting
      multiple sclerosis. It acts by targeting CD52, an antigen primarily expressed on
      T and B lymphocytes, resulting in their depletion and subsequent repopulation.
      The alemtuzumab clinical development program used an active comparator,
      subcutaneous interferon beta-1a, to show that alemtuzumab is a highly efficacious
      disease-modifying therapy, with benefits on relapses, disability outcomes, and
      freedom from clinical disease and magnetic resonance imaging activity. The safety
      profile was consistent across studies and no new safety signals have emerged
      during follow-up in the extension study. Infusion-associated reactions are common
      with alemtuzumab, but rarely serious. Infection incidence was elevated with
      alemtuzumab in clinical studies; most infections were mild or moderate in
      severity. Autoimmune adverse events occurred in approximately a third of
      patients, manifesting mainly as thyroid disorders, and less frequently as immune
      thrombocytopenia or nephropathy. A comprehensive monitoring program lasting at
      least 4 years after the last alemtuzumab dose allows early detection and
      effective management of autoimmune adverse events. Further experience with
      alemtuzumab in the clinic will provide needed long-term data. 

PMID- 25584073
TI  - The pharmacological profile and clinical prospects of the oral 5-HT1F receptor
      agonist lasmiditan in the acute treatment of migraine.
AB  - More than 20 years have passed without the launch of a new substance class for
      acute migraine therapy. Triptans were the latest class of substances which
      successfully passed all developmental stages with a significant antimigraine
      efficacy and a sufficient safety profile. New drugs with a better adverse event
      profile and at least similar efficacy are needed for migraine subjects who cannot
      tolerate triptans for attack treatment. Lasmiditan is a novel highly specific 5
      HT1F receptor agonist currently in clinical trials for acute migraine therapy and
      devoid of vasoconstriction in coronary arteries as determined in a surrogate
      assay. In both phase II randomized, placebo-controlled trials in acute migraine
      the primary endpoint was met. For the intravenous formulation a clear dose
      dependent effect on headaches could be determined. Lasmiditan tablets in doses of
      50-400 mg show significant headache relief after 2 hours compared with placebo
      and improved accompanying symptoms. This substance is chemically clearly
      different from other antimigraine drugs, which is also reflected by its dose
      dependent adverse event profile chiefly including dizziness, vertigo, paresthesia
      and fatigue. Adverse events are usually linked to the central nervous system.
      Future phase III clinical trials with an active triptan comparator or in a
      preferential trial design will allow a better comparison of lasmiditan and
      triptans. They will also determine whether lasmiditan will become available to
      the migraine patient. 

PMID- 25584075
TI  - Parent-offspring association of metabolic syndrome in the Framingham Heart Study.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a clustering of five metabolic risk
      factors including abdominal obesity, elevated blood pressure,
      hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and
      impaired fasting glucose. Few studies have fully reported the strength of
      clustering of these risk factors in a parent-offspring relationship. This
      analysis describes the associations between parents and their adult offspring in
      regard to MetS. It also estimates the association between each risk factor in
      parents and the presence of MetS in their offspring. METHODS: We analyzed data
      for 1193 offspring (565 sons, and 628 daughters) from the Framingham Offspring
      Study who attended examinations 5, 6, and 7. Information about their parents was
      collected from examinations 13, 14 and 15 of the Framingham Original Cohort
      study. We used pedigree file to combine parental and offspring's data.
      Participants were classified as having the MetS according to the Adult Treatment
      Panel III criteria. Analyses were conducted separately for mothers and fathers.
      Logistic regression was used to estimate the associations. RESULTS: After
      adjusting for age, education, smoking, alcohol consumption and physical activity
      level of offspring, no significant association was found between father's and
      their offspring's MetS. Mother's MetS was significantly and positively associated
      with their daughter's MetS (adjusted odds ratio or adj OR: 1.63; 95% confidence
      Interval, CI:1.02-2.61), but not with their sons' MetS. When analyzed by
      individual components, maternal impaired glucose (adj OR: 2.03; 95% CI: 1.02-
      9.31), abdominal obesity (adj OR: 1.56; 95% CI: 0.98- 2.55) and low HDL-C (adj
      OR: 2.12; 95% CI: 1.36-3.32) were associated daughter's MetS. Maternal low HDL-C
      and raised total cholesterol showed marginal association with son's MetS. For
      fathers, only impaired glucose (adj OR: 4.91; 95% CI: 2.07- 11.68) was associated
      with their daughter's MetS. CONCLUSIONS: Using the data from Framingham Heart
      Study, we demonstrate differential association of MetS and its components between
      parents and offspring. Mother's MetS was strongly related with daughter's MetS,
      but the association was inconsistent with son's MetS. No association was found
      between father's MetS and offspring's Mets. These results provide evidence that
      daughters with mother's MetS are in higher risk than daughters or sons with
      father's MetS.

PMID- 25584076
TI  - The physical influence of inositides-a disproportionate effect?
AB  - After the initial observation that lipids form a considerable part of biological
      membranes, the details of the physical role of lipids in biological systems have
      emerged gradually. There have been few 'Eureka' moments in which a class or
      individual lipid has appeared as a game-changing physical player. However,
      evidence collected in the last five years suggests that that notion may be about
      to change. In chemical biology studies, inositides are increasingly showing
      themselves to be lipids that have a physical influence on membrane systems that
      is as strong as their biological (signalling) one. Additionally, recent evidence
      has shown that the concentration of at least one inositide changes during
      important stages of the cell cycle, and not in a manner consistent with its
      traditional signalling roles. The balance between these data is explored and a
      forward-looking view is proposed. 

PMID- 25584077
TI  - Identification of a new pharmacological activity of the phenylpiperazine
      derivative naftopidil: tubulin-binding drug.
AB  - The phenylpiperazine derivative naftopidil is an alpha1-adrenoceptor (AR)
      antagonist that has been used clinically to treat benign prostatic hyperplasia.
      In our drug repositioning research, naftopidil shows the unique growth-inhibitory
      effects. Naftopidil inhibits cell cycle progression not only in cancer cells, but
      also in fibroblasts and vascular endothelial cells. Naftopidil-inhibited cell
      cycle progression is independent of alpha1-AR expression in cells. Therefore, the
      antiproliferative effects of naftopidil may be due to the off-target effects of
      the drug. In this study, we attempted to identify the off-target molecules of
      naftopidil using the magnetic nanobeads, ferrite glycidyl metharcrylate (FG)
      beads. Similar to naftopidil, its derivatives TG09-01 and TG09-02, which were
      introduced with amino groups for immobilizing to FG beads, inhibited cell growth
      in human HT29 colon adenocarcinoma cells. Both derivatives were associated with
      inhibition of cell cycle progression in HT29 cells. This observation is
      consistent with that seen with naftopidil. Using TG09-02-immobilized FG beads,
      alpha- and beta-tubulins were identified as the specific binding proteins of
      naftopidil. The tubulin polymerization assay clearly indicated that naftopidil
      bound directly to tubulin and inhibited the polymerization of tubulin. Other
      phenylpiperazine derivatives, such as RS100329, BMY7378, and KN-62, also
      inhibited the polymerization of tubulin. These results suggest that
      phenylpiperazine derivatives including naftopidil may have broad spectrum of
      cellular cytotoxicity in various types of cells. In addition, the tubulin
      polymerization-inhibiting activity of phenylpiperazine derivatives may be a
      specific feature of the phenylpiperazine-based structure. These findings can
      allow us to design and synthesize new tubulin-binding drugs derived from
      naftopidil as a lead compound. 

PMID- 25584074
TI  - Galacto-oligosaccharides and Colorectal Cancer: Feeding our Intestinal Probiome.
AB  - Prebiotics are ingredients selectively fermented by the intestinal microbiota
      that promote changes in the microbial community structure and/or their
      metabolism, conferring health benefits to the host. Studies show that beta (1-4)
      galacto-oligosaccharides [beta (1-4) GOS], lactulose and fructo-oligosaccharides
      increase intestinal concentration of lactate and short chain fatty acids, and
      stool frequency and weight, and they decrease fecal concentration of secondary
      bile acids, fecal pH, and nitroreductase and beta-glucuronidase activities
      suggesting a clear role in colorectal cancer (CRC) prevention. This review
      summarizes research on prebiotics bioassimilation, specifically beta (1-4) GOS,
      and their potential role in CRC. We also evaluate research that show that the
      impact of prebiotics on host physiology can be direct or through modulation of
      the gut intestinal microbiome, specifically the probiome (autochtonous beneficial
      bacteria), we present studies on a potential role in CRC progression to finally
      describe the current state of beta (1-4) GOS generation for industrial
      production.

PMID- 25584080
TI  - JOCB Bulletin.

PMID- 25584078
TI  - Targeting the cyclin-binding groove site to inhibit the catalytic activity of
      CDK2/cyclin A complex using p27(KIP1)-derived peptidomimetic inhibitors.
AB  - Functionally activated cyclin-dependent kinase 2 (CDK2)/cyclin A complex has been
      validated as an interesting therapeutic target to develop the efficient
      antineoplastic drug based on the cell cycle arrest. Cyclin A binds to CDK2 and
      activates the kinases as well as recruits the substrate and inhibitors using a
      hydrophobic cyclin-binding groove (CBG). Blocking the cyclin substrate
      recruitment on CBG is an alternative approach to override the specificity hurdle
      of the currently available ATP site targeting CDK2 inhibitors. Greater
      understanding of the interaction of CDK2/cyclin A complex with p27 (negative
      regulator) reveals that the Leu-Phe-Gly (LFG) motif region of p27 binds with the
      CBG site of cyclin A to arrest the malignant cell proliferation that induces
      apoptosis. In the present study, Replacement with Partial Ligand Alternatives
      through Computational Enrichment (REPLACE) drug design strategies have been
      applied to acquire LFG peptide-derived peptidomimetics library. The
      peptidomimetics function is equivalent with respect to substrate p27 protein
      fashion but does not act as an ATP antagonist. The combined approach of molecular
      docking, molecular dynamics (MD), and molecular electrostatic potential and
      ADME/T prediction were carried out to evaluate the peptidomimetics. Resultant
      interaction and electrostatic potential maps suggested that smaller substituent
      is desirable at the position of phenyl ring to interact with Trp217, Arg250, and
      Gln254 residues in the active site. The best docked poses were refined by the MD
      simulations which resulted in conformational changes. After equilibration, the
      structure of the peptidomimetic and receptor complex was stable. The results
      revealed that the various substrate protein-derived peptidomimetics could serve
      as perfect leads against CDK2 protein. 

PMID- 25584081
TI  - News from the NIH: Diversity, disparities, and disabilities research.

PMID- 25584079
TI  - Mitochondrial protein alterations in a familial peripheral neuropathy caused by
      the V144D amino acid mutation in the sphingolipid protein, SPTLC1.
AB  - Axonal degeneration is the final common path in many neurological disorders.
      Subsets of neuropathies involving the sensory neuron are known as hereditary
      sensory neuropathies (HSNs). Hereditary sensory neuropathy type I (HSN-I) is the
      most common subtype of HSN with autosomal dominant inheritance. It is
      characterized by the progressive degeneration of the dorsal root ganglion (DRG)
      with clinical symptom onset between the second or third decade of life.
      Heterozygous mutations in the serine palmitoyltransferase (SPT) long chain
      subunit 1 (SPTLC1) gene were identified as the pathogenic cause of HSN-I.
      Ultrastructural analysis of mitochondria from HSN-I patient cells has displayed
      unique morphological abnormalities that are clustered to the perinucleus where
      they are wrapped by the endoplasmic reticulum (ER). This investigation defines a
      small subset of proteins with major alterations in abundance in mitochondria
      harvested from HSN-I mutant SPTLC1 cells. Using mitochondrial protein isolates
      from control and patient lymphoblasts, and a combination of 2D gel
      electrophoresis, immunoblotting and mass spectrometry, we have shown the
      increased abundance of ubiquinol-cytochrome c reductase core protein 1, an
      electron transport chain protein, as well as the immunoglobulin, Ig kappa chain
      C. The regulation of these proteins may provide a new route to understanding the
      cellular and molecular mechanisms underlying HSN-I. 

PMID- 25584082
TI  - e-Health intervention development: a synopsis and comment on "What Design
      Features are Used in Effective e-Health Interventions? A Review Using Techniques
      From Critical Interpretive Synthesis".
AB  - In this synopsis and commentary on the Morrison and colleagues article published
      in Telemedicine and e-Health (18:2, 137-144, 2012), we provide a brief review of
      effective design features of e-Health interventions as well as a discussion on
      future directions. The Internet is being used more frequently to deliver health
      behavior interventions; however, it is unclear which design features contribute
      to intervention outcomes. Morrison and colleagues conducted a review using
      critical interpretive synthesis techniques to identify design features that
      mediate the effects of e-Health intervention outcomes. A total of four design
      features were identified (social context and support, contacts with intervention,
      tailoring, and self-management) that may mediate the effect of the intervention
      on outcomes. This review provides a preliminary conceptual framework to guide
      future evaluations of the effects of e-Health design features on intervention
      outcomes. Future research should target optimizing e-Health interventions to
      determine which design features should be included as well as how they contribute
      to outcomes. 

PMID- 25584083
TI  - Social support for physical activity-role of Facebook with and without structured
      intervention.
AB  - Despite their widespread use and extensive technical features, little is known
      about how to use online social networking sites to increase physical activity.
      This study aims to examine Facebook engagement among participants in the online
      social networking arm of a randomized controlled physical activity promotion
      trial (n = 67). Facebook communications were double coded and analyzed using
      ATLAS.ti. Regression procedures were used to determine predictors of Facebook use
      and associations between types of use and changes in perceived social support and
      physical activity. Changes in perceived social support and physical activity were
      more strongly associated with participants' individual Facebook use than use of
      the Facebook intervention group. The way social media sites are used in
      intervention design could have an impact on their effects. Including existing
      friends in interventions and using applications that incorporate intervention
      activities into a more naturalistic use of Facebook may improve the efficacy of
      future interventions. 

PMID- 25584084
TI  - Varying social media post types differentially impacts engagement in a behavioral
      weight loss intervention.
AB  - The purpose of this study was to examine whether different types of posts
      differentially affect participant engagement and if engagement with social media
      enhances weight loss. Data are a subanalysis from a randomized weight loss study
      with a 4-month follow-up support period via private Facebook groups and monthly
      meetings. Counselors posted five different post types/week based on social
      cognitive theory (weight-related, recipes, nutrition information, poll votes, or
      requests for suggestions). Types of participant engagement (likes, comments/poll
      votes, and views) were assessed. Poll votes were the most engaging (mean number
      of votes or comments/poll 14.6 +/- 3.4, P < 0.01) followed by suggestions (9.1 +/
      2.7 posts, P < 0.01) and weight-related posts (7.4 +/- 3.1 posts, P < 0.01).
      Engagement with Facebook was significantly associated with weight loss during the
      4-month maintenance period (B = -0.09, P = 0.04). The findings provide evidence
      for ways to provide social support during weight loss interventions using remote
      methodology. 

PMID- 25584085
TI  - Evaluating and selecting mobile health apps: strategies for healthcare providers
      and healthcare organizations.
AB  - Mobile applications (apps) to improve health are proliferating, but before
      healthcare providers or organizations can recommend an app to the patients they
      serve, they need to be confident the app will be user-friendly and helpful for
      the target disease or behavior. This paper summarizes seven strategies for
      evaluating and selecting health-related apps: (1) Review the scientific
      literature, (2) Search app clearinghouse websites, (3) Search app stores, (4)
      Review app descriptions, user ratings, and reviews, (5) Conduct a social media
      query within professional and, if available, patient networks, (6) Pilot the
      apps, and (7) Elicit feedback from patients. The paper concludes with an
      illustrative case example. Because of the enormous range of quality among apps,
      strategies for evaluating them will be necessary for adoption to occur in a way
      that aligns with core values in healthcare, such as the Hippocratic principles of
      nonmaleficence and beneficence. 

PMID- 25584086
TI  - Telephone-based motivational interviewing for medication adherence: a systematic
      review.
AB  - Adherence to prescribed medications continues to be a problem in the treatment of
      chronic disease. Motivational interviewing (MI) has been shown to be successful
      for eliciting patients' motivations to change their medication-taking behaviors.
      Due to the constraints of the US healthcare system, patients do not always have
      in-person access to providers. Because of this, there is increasing use of non
      traditional healthcare delivery methods such as telephonic counseling. A
      systematic review was conducted among published studies of telephone-based MI
      interventions aimed at improving the health behavior change target of medication
      adherence. The goals of this review were to (1) examine and describe evidence and
      gaps in the literature for telephonically delivered MI interventions for
      medication adherence and (2) discuss the implications of the findings for
      research and practice. The MEDLINE, CINAHL, psycINFO, psycARTICLES, Academic
      Search Premier, Alt HealthWatch, Health Source: Consumer Edition, and Health
      Source: Nursing/Academic Edition databases were searched for peer-reviewed
      research publications between 1991 and October 2012. A total of nine articles
      were retained for review. The quality of the studies and the interventions varied
      significantly, which precluded making definitive conclusions but findings among a
      majority of retained studies suggest that telephone-based MI may help improve
      medication adherence. The included studies provided promising results and
      justification for continued exploration in the provision of MI via telephone
      encounters. Future research is needed to address gaps in the current literature
      but the results suggest that MI may be an efficient option for healthcare
      professionals seeking an evidence-based method to reach remote or inaccessible
      patients to help them improve their medication adherence. 

PMID- 25584087
TI  - Five population-based interventions for smoking cessation: a MOST trial.
AB  - Little is known about the relative, additive, and interactive effects of
      different population-based treatments for smoking cessation. The goal of this
      study was to evaluate the main and interactive effects of five different smoking
      interventions. Using the multiphase optimization strategy (MOST), 1,034 smokers
      who entered a Web site for smokers (smokefree.gov) were randomly assigned to the
      "on" and "off" conditions of five smoking cessation interventions: the National
      Cancer Institute's (NCI) Web site (www.smokefree.gov vs a "lite" Web site),
      telephone quitline counseling (vs none), a smoking cessation brochure (vs a lite
      brochure), motivational e-mail messages (vs none), and mini-lozenge nicotine
      replacement therapy (NRT vs none). Analyses showed that the NCI Web site and NRT
      both increased abstinence; however, the former increased abstinence significantly
      only when it was not used with the e-mail messaging intervention (messaging
      decreased Web site use). The other interventions showed little evidence of
      effectiveness. There was evidence that mailed nicotine mini-lozenges and the NCI
      Web site (www.smokefree.gov) provide benefit as population-based smoking
      interventions. 

PMID- 25584088
TI  - Smoking cessation: a community-based approach to continuing medical education.
AB  - Continuing medical education can help close the gaps between current and desired
      tobacco cessation practices. This paper reports a case of an innovative community
      based continuing education approach implemented by a multi-organizational
      initiative aimed at increasing smoking cessation rates among adults in the USA.
      The approach involved collaborative partnerships with healthcare professionals
      and other stakeholders in 14 communities where smoking cessation was an
      established priority. The centralized evidence-based educational curriculum was
      delivered locally to more than 15,600 clinicians. Evaluation provided evidence of
      positive impact on clinicians, healthcare systems, and communities. A
      collaborative, community-based approach to continuing medical education has
      potential to increase tobacco cessation rates by leveraging efforts of multiple
      stakeholders operating at the community level into more effective and sustainable
      tobacco cessation projects. Future research is needed to study effectiveness of
      and appropriate evaluation frameworks for this approach. 

PMID- 25584089
TI  - Effects of chronic disease self-management programs for participants with higher
      depression scores: secondary analyses of an on-line and a small-group program.
AB  - Depression often accompanies chronic illness. Study aims included determining (1)
      the level of current depression (Patient Health Questionnaire (PHQ)-8 >= 10) for
      two sets of Chronic Disease Self-Management Programs (CDSMP) participants; (2) if
      depression or other outcomes improved for those with PHQ-8 >= 10; and (3) if
      outcomes differed for participants with or without depression. This study
      utilized longitudinal secondary data analysis of depression cohorts (PHQ-8 >= 10)
      from two independent translational implementations of the CDSMP, small-group (N =
      175) and Internet-based (N = 110). At baseline, 27 and 55  % of the two samples
      had PHQ-8 10 or greater. This decreased to 16 and 37  % by 12  months (p <
      0.001). Both depressed and non-depressed cohorts demonstrated improvements in
      most 12-month outcomes (pain, fatigue, activity limitations, and medication
      adherence). The CDSMP was associated with long-term improvements in depression
      regardless of delivery mode or location, and the programs appeared beneficial for
      participants with and without depression. 

PMID- 25584090
TI  - Control condition design and implementation features in controlled trials: a meta
      analysis of trials evaluating psychotherapy for depression.
AB  - ABSTRACT: Control conditions are the primary methodology used to reduce threats
      to internal validity in randomized controlled trials (RCTs). This meta-analysis
      examined the effects of control arm design and implementation on outcomes in RCTs
      examining psychological treatments for depression. A search of MEDLINE, PsycINFO,
      and EMBASE identified all RCTs evaluating psychological treatments for depression
      published through June 2009. Data were analyzed using mixed-effects models. One
      hundred twenty-five trials were identified yielding 188 comparisons. Outcomes
      varied significantly depending control condition design (p < 0.0001).
      Significantly smaller effect sizes were seen when control arms used manualization
      (p = 0.006), therapist training (p = 0.002), therapist supervision (p = 0.009),
      and treatment fidelity monitoring (p = 0.003). There were no significant effects
      for differences in therapist experience, level of expertise in the treatment
      delivered, or nesting vs. crossing therapists in treatment arms. These findings
      demonstrate the substantial effect that decisions regarding control arm
      definition and implementation can have on RCT outcomes.

PMID- 25584091
TI  - Implementing a brief evidence-based HIV intervention: a mixed methods examination
      of compliance fidelity.
AB  - Dissemination of HIV behavioral prevention programs has increased the reach of
      evidence-based interventions, but there is a paucity of data on implementation
      and diffusion. The present mixed methods study focused on RESPECT, a brief
      counseling and testing intervention, examining compliance fidelity and the extent
      to which Centers for Disease Control and Prevention (CDC) policies and training
      have diffused to practice settings. Using client exit surveys (N = 830) and
      counselor interviews (N = 64), we examined implementation in 26 community-based
      agencies (CBOs) and public health departments (DPHs) in the USA. Multivariate
      analyses showed that at-risk clients, ethnic minority clients, and those who were
      primarily seeking services other than HIV/STI testing, were more likely to
      receive the program with fidelity. Counselor data suggested that multiple factors
      (e.g., client characteristics, agency structure) impact program adaptations.
      RESPECT is being delivered with good fidelity and reaching at-risk clients. The
      data provide support for CDC diffusion efforts. Future studies should continue to
      examine compliance fidelity and program sustainability. 

PMID- 25584092
TI  - The window of opportunity for indoor tanning legislation.
AB  - As of August 2014, 11 states in the USA have passed under-age-18 bans on indoor
      tanning. The Society of Behavioral Medicine, the American Academy of Dermatology,
      and the American Academy of Pediatrics have all issued statements in support of
      an under-age-18 ban. The World Health Organization and the Food and Drug
      Administration have both declared indoor tanning devices as carcinogenic, and
      this year, the Surgeon General for the first time issued a warning on the dangers
      of UV radiation and indoor tanning. This essay highlights how the awareness of
      the risks of indoor tanning, effective policies, and a conducive political
      atmosphere have aligned to create a window of opportunity for further under-age
      18 indoor tanning legislation. The rising number of preventable skin cancers and
      mortalities is an issue that transcends political party lines, and now, there is
      a need for support from health professionals and advocates to motivate
      legislators to push new under-age-18 bills past their sticking points. 

PMID- 25584093
TI  - Society of Behavioral Medicine position statement: elementary school-based
      physical activity supports academic achievement.
AB  - The Society of Behavioral Medicine (SBM) urges elementary schools to provide
      children with ample opportunities to engage in physical activity during school
      hours. In addition to promoting overall child health, physical activity also
      supports academic achievement. In addition to improving their aerobic fitness,
      regular physical activity improves cognitive function, influences the brain, and
      improves mood in children. Better aerobic fitness and physical activity are
      associated with increased grade point averages and standardized test scores.
      Despite the documented relationship between physical activity, fitness, and
      academic achievement, few schools have implemented physical activity as a tool to
      improve academic performance. SBM recommends that elementary schools provide
      children with the recommended 60 min of moderate-to-vigorous physical activity
      during school hours. Further, SBM urges schools to work with the local school
      districts and state education departments to mandate minimum physical activity
      time for elementary school physical education. 

PMID- 25584094
TI  - Sjogren's, Renal Tubular Acidosis And Osteomalacia - An Asian Indian Series.
AB  - OBJECTIVE: To study the profile of Renal Tubular Acidosis (RTA) in Asian Indian
      patients with Primary Sjogren's Syndrome (pSS). METHODS: The Electronic medical
      records of patients with a diagnosis of pSS seen between 2003 and 2010 at our
      tertiary care teaching hospital were screened for RTA. Clinical features,
      immunological profile, acid-base balance and electrolyte status, 25
      hydroxyvitamin D (25(OH) D3) levels, histopathological changes in minor salivary
      gland biopsy samples and radiological findings were retrieved. RTA was diagnosed
      in cases of hyperchloremic metabolic acidosis with urinary pH values higher than
      5.5. Those with known features suggestive of RTA including hypokalemic paralysis,
      hyperchloremia and nephrocalcinosis without acidosis were defined as incomplete
      RTA. RESULTS: Of the 380 patients with clinically suspected pSS, 25 had RTA. The
      median age was 32 (18-60) years. Nineteen patients had complete RTA. Six had
      incomplete RTA. Only 10 patients (40%) had symptoms related to RTA at
      presentation. Sixteen patients (64%) had present or past history of hypokalemic
      paralysis. Pseudofractures were seen in 7 patients and an additional 2 had
      subclinical radiological osteomalacia. Majority of the patients (61.2%) had a
      normal 25(OH) D3 level. Those with osteomalacia had significantly lower serum
      phosphate, blood ph and higher alkaline phosphatase. Serum calcium and 25(OH) D3
      levels were not significantly different between patients with osteomalacia and
      those without. CONCLUSION: Most patients were asymptomatic for RTA inspite of
      clinically overt and elicitable features. Skeletal manifestation was a common
      finding in patients with Sjogren and RTA, despite normal levels of 25 (OH) D3 in
      a majority.

PMID- 25584095
TI  - Bioactive indole alkaloids isolated from Alstonia angustifolia.
AB  - Bioassay-guided fractionation was conducted on a CHCl3-soluble extract of the
      stem bark of Alstonia angustifolia (Apocynaceae) collected in Vietnam using the
      HT-29 human colon cancer cell line, and led to the isolation of a new sarpagine
      type indole alkaloid (1), together with nine known alkaloids, including four
      macroline-derived alkaloids (2-5), a sarpagine-type alkaloid (6), and four
      macroline-pleiocarpamine bisindole alkaloids (7-10). The structure of the new
      compound (1) was determined on the basis of spectroscopic data interpretation.
      Compounds 1-10 were evaluated in vitro for their NF-kappaB (p65) inhibitory
      activity against the Hela cells in an ELISA assay. The new sarpagine alkaloid,
      N(4)-methyltalpinine (1), was found to show significant NF-kappaB inhibitory
      activity (ED50 = 1.2 uM). Furthermore, all the isolates (1-10) were evaluated in
      vitro for their antileishmanial activity, and compounds (1-4, 6 and 8-10)
      exhibited leishmaniacidal activity against promastigotes of Leishmania mexicana.

PMID- 25584096
TI  - Computed tomography features of pulmonary nocardiosis in immunocompromised and
      immunocompetent patients.
AB  - BACKGROUND: Nocardiosis primarily occurs in the setting of immunocompromising
      conditions. However, it may also occur in immunocompetent patients. We described
      computed tomography features of pulmonary nocardiosis and compared
      immunocompetent and immunocompromised patients. MATERIAL/METHODS: CT images of 25
      patients (Mean age of 39.5 years; 76% male) with pulmonary nocardiosis proved by
      bronchoalveolar lavage or biopsy were reviewed by two experienced pulmonary
      radiologists and detailed findings were reported on. Fourteen patients (56%) were
      immunocompetent, while 44% had an underlying immunocompromising condition,
      including chronic granulomatous disease (CGD) (n=4), diabetes mellitus (DM)
      (n=2), malignancy (n=2), HIV (n=1), concomitant CGD and DM (n=1), and steroid
      therapy for nephrotic syndrome (n=1). RESULTS: Most patients had bilateral
      involvement with no zonal predominance. Multiple pulmonary nodules (96%) were the
      most common CT findings, followed by consolidation (76%) and cavity (52%). Other
      findings included bronchiectasis (48%), pleural thickening (40%), ground glass
      opacity (32%), mass-like consolidation (20%), intrathoracic lymphadenopathy
      (16%), pleural effusion (12%), reticular infiltration (4%), and pericardial
      effusion (4%). There was no statistically significant difference in the CT
      findings of immunocompromised and immunocompetent groups. CONCLUSIONS: Pulmonary
      nocardiosis presents mainly as multiple pulmonary nodules, consolidations, and
      cavity in both immunocompromised and immunocompetent patients. However, these
      features are more suggestive of nocardiosis in the setting of an underling
      immunocompromised condition.

PMID- 25584098
TI  - Effects of Dietary Fat Intake on HDL Metabolism.
AB  - High-density lipoprotein (HDL) is a lipoprotein which has anti-atherogenic
      property by reversing cholesterol transport from the peripheral tissues to liver.
      Low HDL-cholesterol (HDL-C) as well as high low-density lipoprotein-cholesterol
      (LDL-C) is associated with the development of coronary heart diseases (CHD).
      Various epidemiological studies have suggested that the development of CHD
      increase in individuals with less than 40 mg/dL of HDL-C. In spite of
      accumulation of evidences suggesting a significant association between low HDL-C
      and CHD, effects of dietary factors on HDL metabolism remained largely unknown.
      We reviewed published articles about effects of dietary fat intake on HDL
      metabolism. The substitution of fatty acids (FA) for carbohydrates is
      beneficially associated with HDL metabolism. Monounsaturated FA intake may not
      affect HDL-C. Trans-FA is significantly associated with reduction of HDL-C, and
      is also adversely related with total cholesterol/HDL-C. Fish oils consumption,
      especially docosahexaenoic acid consumption, may be favorably associated with HDL
      metabolism. Although plant sterols and stanols may not affect HDL-C, policosanol
      intake is associated with a clinically significant decrease in the LDL/HDL ratio.

PMID- 25584099
TI  - Clinical significance of precipitous labor.
AB  - BACKGROUND: Precipitous labor is defined as expulsion of the fetus within less
      than 3 hours of commencement of regular contractions. We retrospectively examined
      our cases of precipitous labor to identify the clinical significance and
      perinatal outcomes following precipitous labor in singleton vertex deliveries.
      METHODS: A retrospective population-based study was conducted comparing women
      with singleton precipitous labor and those with labor of normal duration. We
      examined the clinical characteristics and outcomes by comparing patients with
      precipitous labor and those with labor of normal duration in 0 and two-parous
      singleton pregnant women. RESULTS: Using a multivariate analysis, precipitous
      labor in nulliparous women was independently associated with teenagers (adjusted
      OR: 1.71, 95% CI: 0.99 - 2.95, P = 0.049), preterm delivery (adjusted OR: 1.77,
      95% CI: 1.16 - 2.70, P < 0.01) and hypertensive disorders (adjusted OR: 1.77, 95%
      CI: 1.19 - 2.65, P < 0.01), while in two-parous women, it was independently
      associated with hypertensive disorders (adjusted OR: 2.64, 95% CI: 1.33 - 5.24, P
      < 0.01). No significant differences were noted between the two groups regarding
      maternal or neonatal complications on both nulliparous and two-parous women.
      CONCLUSION: Although precipitous labor was associated with hypertensive disorders
      in singleton vertex deliveries, it was not associated with maternal or neonatal
      outcomes.

PMID- 25584100
TI  - Reduced heart function predicts drug-taking compliance and two-year prognosis in
      chinese patients with stable premature coronary artery disease.
AB  - BACKGROUND: The purpose of this study was to determine the association between
      heart function, compliance with drug administration, and the mid-term prognosis
      in Chinese patients with stable premature coronary artery disease (CAD) (male <
      55 years and female < 65 years). METHODS: The study included 512 patients with
      stable premature CAD. An estimated glomerular filtration rate (eGFR) calculated
      using the MDRD formula, baseline clinical characteristics, use of medications for
      coronary secondary prevention therapies (aspirin, beta-blocker, angiotensin
      converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers, or
      statins), and 2-year follow-up results, in particular major adverse cardiac
      events (MACEs), were collected and analyzed. RESULTS: Patients with reduced left
      ventricular ejection fraction (LVEF) (18.75%) were more prevalent among men,
      smokers, those with type 2 diabetes, with a family history of cardiovascular
      disease (CVD), and with higher white blood cells counts ((8.88 +/- 0.35) *
      10(9)/L vs. (6.90 +/- 0.17) * 10(9)/L) (all P < 0.05) compared to those with
      preserved LVEF. There was no significant difference between creatinine or eGFR
      values in the two groups with reduced and preserved LVEF (all P > 0.05). Patients
      with LVEF < 50% in the MACEs group had a lower ratio of optimal drug
      administration compared to the MACEs-free group (Z = -0.228, P = 0.820 and Z = 
      2.167, P = 0.03 respectively). Patients with reduced LVEF had a significantly
      higher ratio of composite MACEs than patients with preserved LVEF during 2-year
      follow-up (47.13% vs. 33.50%, P < 0.05). CONCLUSIONS: Stable premature CAD
      patients with reduced LVEF have more risk factors, lower medication compliance,
      and worse 2-year outcomes than those with preserved LVEF.

PMID- 25584097
TI  - Left ventricular diastolic function in hypertension: methodological
      considerations and clinical implications.
AB  - The assessment of left ventricular (LV) diastolic function should be an integral
      part of a routine examination of hypertensive patient; indeed when LV diastolic
      function is impaired, it is possible to have heart failure even with preserved LV
      ejection fraction. Left ventricular diastolic dysfunction (LVDD) occurs
      frequently and is associated to heart disease. Doppler echocardiography is the
      best tool for early LVDD diagnosis. Hypertension affects LV relaxation and when
      left ventricular hypertrophy (LVH) occurs, it decreases compliance too, so it is
      important to calculate Doppler echocardiography parameters, for diastolic
      function evaluation, in all hypertensive patients. The purpose of our review was
      to discuss about the strong relationship between LVDD and hypertension, and their
      relationship with LV systolic function. Furthermore, we aimed to assess the
      relationship between the arterial stiffness and LV structure and function in
      hypertensive patients. 

PMID- 25584101
TI  - The Burden of JAK2V617F Mutated Allele in Turkish Patients With
      Myeloproliferative Neoplasms.
AB  - BACKGROUND: Studies regarding the impact of JAK2V617F allele burden on phenotypic
      properties and clinical course in Philadelphia-negative myeloproliferative
      neoplasms (Ph-negative MPNs) have reported variable results. We aimed to analyze
      the association of mutated JAK2V617F allele burden with laboratory
      characteristics and clinical phenotype in Turkish patients (107 essential
      thrombocythemia (ET) and 77 primary myelofibrosis (PMF)). METHODS: Peripheral
      blood samples of 184 patients with Ph-negative MPNs were analyzed for JAK2V617F
      allele status and burden. JAK2 MutaScreen assay (Ipsogen, Luminy Biotech,
      Marseille, France) was used to detect the JAK2V617F status and quantitative
      JAK2V617F allele burdens in genomic DNA using TaqMan allelic discrimination.
      RESULTS: Frequency of JAK2V617F-positive patients with high mutation load (allele
      burden > 50%) was higher in PMF compared to ET (23.4% and 4.7%, respectively; P =
      0.001). We found significant association between ET patients with high JAK2V617F
      allele burden and lower hemoglobin (Hgb) and hematocrit (Hct), higher LDH levels
      and more prevalent massive splenomegaly (P = 0.001, P = 0.001, P = 0.012 and P =
      0.015, respectively). ET patients with high mutation load displayed higher
      prevalence of bleeding compared to low mutation load and wild-type mutational
      status (P = 0.003). Rate of DVT was significantly higher in ET patients with
      mutant allele burden in upper half compared to lower half and wild-type (P =
      0.029). We observed significant association between PMF patients with high
      JAK2V617F allele burden and higher Hgb, Hct levels and leukocyte counts (P =
      0.003, P = 0.021 and P = 0.001, respectively). CONCLUSIONS: Our study
      demonstrated JAK2V617F allele burden correlates with clinical features in ET and
      PMF. We conclude quantification of JAK2V617F mutation contributes to the workup
      of Ph-negative MPNs.

PMID- 25584102
TI  - Reduced operating time but not blood loss with cruciate retaining total knee
      arthroplasty.
AB  - BACKGROUND: There is no consensus regarding the use of retaining or replacing
      cruciate implants for patients with limited deformity who undergo a total knee
      replacement. Scope of this paper is to evaluate whether a cruciate sparing total
      knee replacement could have a reduced operating time compared to a posterior
      stabilized implant. METHODS: For this purpose, we performed a randomized study on
      50 subjects. All procedures were performed by a single surgeon in the same
      conditions to minimize bias and only knees with a less than 20 varus deviation
      and/or maximum 15 degrees  fixed flexion contracture were included. RESULTS:
      Surgery time was significantly shorter with the cruciate retaining implant (P =
      0.0037). The mean duration for the Vanguard implant was 68.9 (14.7) and for the
      NexGen II Legacy was 80.2 (11.3). A higher range of motion, but no significant
      Knee Society Scores at 6 months follow-up, was used as controls. CONCLUSIONS: In
      conclusion, both implants had the potential to assure great outcomes. However, if
      a decision has to be made, choosing a cruciate retaining procedure could
      significantly reduce the surgical time. When performed under tourniquet, this
      gain does not lead to reduced blood loss.

PMID- 25584103
TI  - Seroepidemiology of Toxocara infection in patients with vision impairment and
      blindness in durango, Mexico.
AB  - BACKGROUND: Toxocara infection is a cause of vision impairment and blindness. We
      aimed to determine the seroprevalence and correlates of Toxocara infection in
      patients suffering from vision impairment and blindness in Durango City, Mexico.
      METHODS: Through a cross-sectional seroprevalence study, 204 patients with vision
      impairment and 19 blind patients were studied for the presence of anti-Toxocara
      IgG antibodies in Durango City, Mexico. Seroprevalence association with socio
      demographic, housing, clinical, and behavioral characteristics of participants
      was also investigated. RESULTS: Five (2.5%) of the 204 patients with vision
      impairment, and none of the 19 patients with blindness were positive for anti
      Toxocara IgG antibodies. In total, five of the 223 (2.2%) patients were positive
      for anti-Toxocara IgG antibodies. Seropositivity to Toxocara was not associated
      with age, sex, educational level, socio-economic status, presence of underlying
      diseases or behavioral characteristics of the patients. In contrast, multivariate
      analysis showed that Toxocara seropositivity was associated with living in a
      house with soil floor (odds ratio (OR) = 11.14; 95% confidence interval (CI):
      1.57 - 78.74; P = 0.01). CONCLUSIONS: This is the first report of Toxocara
      exposure in patients with vision impairment and blindness in Mexico, and of an
      association of Toxocara exposure with living in a house with soil floors. Results
      suggest a low Toxocara exposure in these patients in Durango, Mexico. The risk
      factor associated with Toxocara exposure identified in this study warrants for
      further investigation.

PMID- 25584104
TI  - The single-leg-stance test in Parkinson's disease.
AB  - BACKGROUND: Timed single-leg-stance test (SLST) is widely used to assess postural
      control in the elderly. In Parkinson's disease (PD), it has been shown that an
      SLST around 10 seconds or below may be a sensitive indicator of future falls.
      However, despite its role in fall risk, whether SLST times around 10 seconds
      marks a clinically important stage of disease progression has largely remained
      unexplored. METHODS: A cross-sectional study where 27 people with PD were
      recruited and instructed to undertake timed SLST for both legs was conducted.
      Disease motor impairment was assessed with the Unified Parkinson's Disease Rating
      Scale Part 3 (UPDRS-III). RESULTS: This study found that: 1) the SLST in people
      with PD shows good test-retest reliability; 2) SLST values can be attributed to
      two non-overlapping clusters: a low (10.4 +/- 6.3 seconds) and a high (47.6 +/-
      11.7 seconds) value SLST group; 3) only the low value SLST group can be
      considered abnormal when age-matched normative SLST data are taken into account
      for comparison; and 4) lower UPDRS-III motor performance, and the bradykinesia
      sub-score in particular, are only associated with the low SLST group. CONCLUSION:
      These results lend further support that a low SLST time around 10 seconds marks a
      clinically important stage of disease progression with significant worsening of
      postural stability in PD.

PMID- 25584105
TI  - Cystic fibrosis and beckwith-wiedemann syndrome: a case report.
AB  - Cystic fibrosis (CF) is a hereditary disease of exocrine gland function that
      involves multiple systems but chiefly results in chronic respiratory infections,
      the major cause of death, pancreatic enzyme deficiency and severe malnutrition,
      mostly in untreated patients. The association between CF and other inherited
      diseases or congenital anomalies is rare. We describe for the first time the
      association of CF and Beckwith-Wiedemann syndrome (BWS). BWS is a genetic
      disorder commonly characterized by overgrowth. The most common features of BWS
      include macrosomia, macroglossia, abdominal wall defects, an increased risk for
      childhood tumors, kidney abnormalities, hypoglycemia in the newborn period and
      unusual ear creases or pits. 

PMID- 25584106
TI  - Deafness and sickle cell disease: three case reports and review of the
      literature.
AB  - The otological complications of sickle cell disease (SCD) in general and the
      audiological complications in particular are not well documented and studied.
      Because the general management of patients with SCD has improved after the advent
      of newborn screening, antibiotic prophylaxis, safer blood transfusion and
      hydroxyurea therapy, patients with SCD are doing better in general and living
      longer than before. With longer longevity, the incidence of new complications of
      SCD became apparent and previously milder complications became more severe and
      more common. The dental and otological complications of SCD are examples of these
      changes that have become more common than before. Unfortunately with this
      increase, there are no guidelines or recommendations based on evidence on how to
      manage and treat these complications. The aim of this study was to describe three
      patients with SCD and deafness due to three different causes that were not
      adequately treated and to review the literature of deafness in SCD. We hope this
      may initiate more controlled trials on the incidence, prevalence and management
      of these complications. 

PMID- 25584107
TI  - Neuromyelitis optica in pregnancy complicated by posterior reversible
      encephalopathy syndrome, eclampsia and fetal death.
AB  - Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic
      neuritis and acute myelitis with poor recovery and a progressive course. We
      report a poor outcome complicated by posterior reversible encephalopathy syndrome
      (PRES) and eclampsia and review available literature and current evidence for
      anticipation of adverse fetal and maternal effects. After a pregnancy complicated
      by multiple admissions for painful NMO exacerbations, a primiparous patient with
      seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent
      fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads
      to adverse maternal and fetal outcomes. Posited mechanisms include antibody
      mediated placental damage and a heightened risk of eclampsia-associated PRES.
      Further characterization of the course of NMO and its relationship with pregnancy
      outcomes in larger series would be invaluable. 

PMID- 25584108
TI  - Coccidioidomycosis and Blastomycosis: Endemic Mycotic Co-Infections in the HIV
      Patient.
AB  - Opportunistic fungal infections including aspergillosis species, candida species,
      and fusarium can be found in HIV-infected patients. Disseminated diseases due to
      endemic mycoses including histoplasmosis, coccidioidomycosis, and blastomycosis
      are all being reported among HIV patients who reside in the known endemic areas.
      However, in the non-endemic areas, or due to the rarity of these pathogens, it
      might be difficult to recognize these unfamiliar disease presentations. We report
      a patient with HIV who had dual infections with endemic mycotic infections of
      coccidioidomycosis and blastomycosis, as he had a brief stay in the endemic area.

PMID- 25584109
TI  - An adrenal mass and increased catecholamines: monoamine oxidase or
      pheochromocytoma effect?
AB  - Hormonal evaluation in patients with an adrenal incidentaloma can be difficult in
      patients with comorbidities or in patients using interfering drugs. We present a
      case of a 54-year-old man who was evaluated for an adrenal mass. The medical
      history reported treatment with a monoamine oxidase (MAO) inhibitor for recurrent
      psychoses. Hormonal screening showed elevated levels of normetanephrine and
      metanephrine in plasma and urine, suggesting a diagnosis of pheochromocytoma
      (PHEO), and an adrenalectomy was performed. Histologic examination showed that
      the tumor had an origin of the adrenal cortex. MAO inhibitors are also known to
      cause elevated levels of catecholamines. In this case, a PHEO seemed more likely
      the cause due to repeatedly elevated levels of metanephrines and normal levels of
      catecholamines. Since the tumor had an origin of the adrenal cortex, the use of
      MAO inhibitors was the most likely explanation for the elevated levels of
      metanephrines. This case illustrated the difficulties in diagnosing PHEO,
      especially in patients with comorbidities and interfering drugs. 

PMID- 25584110
TI  - Fluid interfacial nanoroughness measurement through the morphological
      characteristics of graphene.
AB  - The interfacial nanoroughness of liquid plays an important role in the
      reliability of liquid lenses, capillary waves, and mass transfer in biological
      cells [Grilli et al., Opt. Express 16, 8084 (2008), Wang et al., IEEE Photon.
      Technol. Lett. 18, 2650 (2006), and T. Fukuma et al., 92, 3603 (2007)]. However,
      the nanoroughness of liquid is hard to visualize or measure due to the
      instability and dynamics of the liquid-gas interface. In this study, we blanket a
      liquid water surface with monolayer graphene to project the nanoroughness of the
      liquid surface. Monolayer graphene can project the surface roughness because of
      the extremely high flexibility attributed to its one atomic thickness. The
      interface of graphene and water is successfully mimicked by the molecular
      dynamics method. The nanoroughness of graphene and water is defined based on
      density distribution. The correlation among the roughness of graphene and water
      is developed within a certain temperature range (298-390 K). The results show
      that the roughness of water surface is successfully transferred to graphene
      surface. Surface tension is also calculated with a simple water slab. The rise of
      temperature increased the roughness and decreased the surface tension. Finally,
      the relationship between graphene roughness and surface tension is fitted with a
      second-order polynomial equation. 

PMID- 25584111
TI  - Integration of programmable microfluidics and on-chip fluorescence detection for
      biosensing applications.
AB  - We describe the integration of an actively controlled programmable microfluidic
      sample processor with on-chip optical fluorescence detection to create a single,
      hybrid sensor system. An array of lifting gate microvalves (automaton) is
      fabricated with soft lithography, which is reconfigurably joined to a liquid
      core, anti-resonant reflecting optical waveguide (ARROW) silicon chip fabricated
      with conventional microfabrication. In the automaton, various sample handling
      steps such as mixing, transporting, splitting, isolating, and storing are
      achieved rapidly and precisely to detect viral nucleic acid targets, while the
      optofluidic chip provides single particle detection sensitivity using integrated
      optics. Specifically, an assay for detection of viral nucleic acid targets is
      implemented. Labeled target nucleic acids are first captured and isolated on
      magnetic microbeads in the automaton, followed by optical detection of single
      beads on the ARROW chip. The combination of automated microfluidic sample
      preparation and highly sensitive optical detection opens possibilities for
      portable instruments for point-of-use analysis of minute, low concentration
      biological samples. 

PMID- 25584112
TI  - Deformability-based red blood cell separation in deterministic lateral
      displacement devices-A simulation study.
AB  - We show, via three-dimensional immersed-boundary-finite-element-lattice-Boltzmann
      simulations, that deformability-based red blood cell (RBC) separation in
      deterministic lateral displacement (DLD) devices is possible. This is due to the
      deformability-dependent lateral extension of RBCs and enables us to predict a
      priori which RBCs will be displaced in a given DLD geometry. Several diseases
      affect the deformability of human cells. Malaria-infected RBCs, for example, tend
      to become stiffer than their healthy counterparts. It is therefore desirable to
      design microfluidic devices which can detect diseases based on the cells'
      deformability fingerprint, rather than preparing samples using expensive and time
      consuming biochemical preparation steps. Our findings should be helpful in the
      development of new methods for sorting cells and particles by deformability. 

PMID- 25584113
TI  - Molecularly imprinted electrochemical sensing of urinary melatonin in a
      microfluidic system.
AB  - Melatonin levels may be related to the risks of breast cancer and prostate
      cancer. The measurement of urinary melatonin is also useful in monitoring serum
      melatonin levels following oral administration. In this work, melatonin is the
      target molecule, which is imprinted onto poly(ethylene-co-vinyl alcohol) by
      evaporation of the solvent on the working electrode of an electrochemical sensing
      chip. This sensing chip is used directly as a tool for optimizing the imprinting
      polymer composition, flow rate, and injection volume of the samples. Microfluidic
      sensing of the target and interference molecules revealed that the lowest
      detection limit is as low as ~pM, and the electrochemical response is weak even
      at high interference concentrations. Poly(ethylene-co-vinyl alcohol), containing
      44 mol. % ethylene, had an imprinting effectiveness of more than six-fold. In
      random urine analysis, the microfluidic amperometric measurements of melatonin
      levels with an additional and recovery of melatonin, the melatonin recovery
      achieved 94.78 +/- 1.9% for melatonin at a concentration of 1.75-2.11 pg/mL. 

PMID- 25584114
TI  - A microfluidic device to study cancer metastasis under chronic and intermittent
      hypoxia.
AB  - Metastatic cancer cells must traverse a microenvironment ranging from extremely
      hypoxic, within the tumor, to highly oxygenated, within the host's vasculature.
      Tumor hypoxia can be further characterized by regions of both chronic and
      intermittent hypoxia. We present the design and characterization of a
      microfluidic device that can simultaneously mimic the oxygenation conditions
      observed within the tumor and model the cell migration and intravasation
      processes. This device can generate spatial oxygen gradients of chronic hypoxia
      and produce dynamically changing hypoxic microenvironments in long-term culture
      of cancer cells. 

PMID- 25584115
TI  - Effective cell collection method using collagenase and ultrasonic vibration.
AB  - This study proposes a novel cell collection method based on collagenase treatment
      and ultrasonic vibration. The method collects calf chondrocytes from a reusable
      metal cell culture substrate. To develop our concept, we calculated the natural
      vibration modes of the cell culture substrate by a finite element method, and
      conducted eigenvalue and piezoelectric-structural analyses. Selecting the first
      out-of-plane vibration mode of the substrate, which has a single nodal circle, we
      designed and fabricated the cell collection device. The excited vibration mode
      properly realized our intentions. We then evaluated the cell collection ratio and
      the growth response, and observed the morphology of the collected cells. The
      collagenase and ultrasonic vibration treatment collected comparable numbers of
      cells to conventional trypsin and pipetting treatment, but improved the
      proliferating cell statistics. Morphological observations revealed that the
      membranes of cells collected by the proposed method remain intact; consequently,
      the cells are larger and rougher than cells collected by the conventional method.
      Therefore, we present a promising cell collection method for adhesive cell
      culturing process. 

PMID- 25584116
TI  - Programmed sample delivery on a pressurized paper.
AB  - This paper reports a method to control the fluid flow in paper-based microfluidic
      devices simply by pressing over the channel surface of paper, thereby decreasing
      the pore size and permeability of a non-woven polypropylene sheet. As a result,
      fluid resistance is increased in the pressed region and causes flow rate to
      decrease. We characterize the decrease of flow rate with respect to different
      amounts of pressure applied, and up to 740% decrease in flow velocity was
      achieved. In addition, we demonstrate flow rate control in a Y-shaped merging
      paper and sequential delivery of multiple color dyes in a three-branched paper.
      Furthermore, sequential delivery of multiple fluid samples is performed to
      demonstrate its application in multi-step colorimetric immunoassay, which shows a
      4.3-fold signal increase via enhancement step. 

PMID- 25584117
TI  - Microfluidic reactors for visible-light photocatalytic water purification
      assisted with thermolysis.
AB  - Photocatalytic water purification using visible light is under intense research
      in the hope to use sunlight efficiently, but the conventional bulk reactors are
      slow and complicated. This paper presents an integrated microfluidic planar
      reactor for visible-light photocatalysis with the merits of fine flow control,
      short reaction time, small sample volume, and long photocatalyst durability. One
      additional feature is that it enables one to use both the light and the heat
      energy of the light source simultaneously. The reactor consists of a BiVO4-coated
      glass as the substrate, a blank glass slide as the cover, and a UV-curable
      adhesive layer as the spacer and sealant. A blue light emitting diode panel
      (footprint 10 mm * 10 mm) is mounted on the microreactor to provide uniform
      irradiation over the whole reactor chamber, ensuring optimal utilization of the
      photons and easy adjustments of the light intensity and the reaction temperature.
      This microreactor may provide a versatile platform for studying the
      photocatalysis under combined conditions such as different temperatures,
      different light intensities, and different flow rates. Moreover, the microreactor
      demonstrates significant photodegradation with a reaction time of about 10 s,
      much shorter than typically a few hours using the bulk reactors, showing its
      potential as a rapid kit for characterization of photocatalyst performance. 

PMID- 25584118
TI  - Measurement and control of pressure driven flows in microfluidic devices using an
      optofluidic flow sensor.
AB  - Measurement and control of pressure-driven flow (PDF) has a great potential to
      enhance the performance of chemical and biological experiments in Lab on a Chip
      technology. In this paper, we present an optofluidic flow sensor for real-time
      measurement and control of PDF. The optofluidic flow sensor consists of an on
      chip micro Venturi and two optical Fabry-Perot (FP) interferometers. Flow rate
      was measured from the fringe shift of FP interferometers resulted from movement
      fluid in the on-chip micro Venturi. The experimental results show that the
      optofluidic flow sensor has a minimum detectable flow change of 5 nl/min that is
      suitable for real time monitoring and control of fluids in many chemical and
      biological experiments. A Finite Element Method is used to solve the three
      dimensional (3D) Navier-Stokes and continuity equations to validate the
      experimental results. 

PMID- 25584119
TI  - A simple paper-based sensor fabricated by selective wet etching of silanized
      filter paper using a paper mask.
AB  - We developed a novel strategy for fabrication of microfluidic paper-based
      analytical devices (MUPADs) by selective wet etching of hydrophobic filter paper
      using a paper mask having a specific design. The fabrication process consists of
      two steps. First, the hydrophilic filter paper was patterned hydrophobic by using
      trimethoxyoctadecylsilane (TMOS) solution as the patterning agent. Next, a paper
      mask penetrated with NaOH solution (containing 30% glycerol) was aligned onto the
      hydrophobic filter paper, allowing the etching of the silanized filter paper by
      the etching reagent. The masked region turned highly hydrophilic whereas the
      unmasked region remains highly hydrophobic. Thus, hydrophilic channels,
      reservoirs, and detection zones were generated and delimited by the hydrophobic
      barriers. The effects of some factors including TMOS concentration, etching
      temperature, etching time, and NaOH concentration on fabrication of MUPAD were
      studied. Being free of any expensive equipment, metal mask and expensive
      reagents, this rapid, simple, and cost-effective method could be used to
      fabricate MUPAD by untrained personnel with minimum cost. A flower-shaped MUPAD
      fabricated by this presented method was applied to the glucose assay in
      artificial urine samples with good performance, indicating its feasibility as a
      quantitative analysis device. We believe that this method would be very
      attractive to the development of simple microfluidic devices for point-of-care
      applications in clinical diagnostics, food safety, and environmental protection. 

PMID- 25584120
TI  - FPGA Simulation Engine for Customized Construction of Neural Microcircuits.
AB  - In this paper we describe an FPGA-based platform for high-performance and low
      power simulation of neural microcircuits composed from integrate-and-fire (IAF)
      neurons. Based on high-level synthesis, our platform uses design templates to map
      hierarchies of neuron model to logic fabrics. This approach bypasses high design
      complexity and enables easy optimization and design space exploration. We
      demonstrate the benefits of our platform by simulating a variety of neural
      microcircuits that perform oscillatory path integration, which evidence suggests
      may be a critical building block of the navigation system inside a rodent's
      brain. Experiments show that our FPGA simulation engine for oscillatory neural
      microcircuits can achieve up to 39* speedup compared to software benchmarks on
      commodity CPU, and 232* energy reduction compared to embedded ARM core.

PMID- 25584121
TI  - Phenotypic and genetic characterization of Vibrio cholerae O1 isolated from
      various regions of Kenya between 2007 and 2010.
AB  - INTRODUCTION: Cholera, a disease caused by Vibrio cholerae O1 and O139 remains an
      important public health problem globally. In the last decade, Kenya has
      experienced a steady increase of cholera cases. In 2009 alone, 11,769 cases were
      reported to the Ministry of Public Health and Sanitation. This study sought to
      describe the phenotypic characteristics of the isolated V. cholerae isolates.
      METHODS: This was a laboratory based cross-sectional study that involved isolates
      from different cholera outbreaks. Seventy six Vibrio cholerae O1 strains from
      different geographical areas were used to represent 2007 to 2010 cholera
      epidemics in Kenya, and were characterized by serotyping, biotyping, polymerase
      chain r(PCR), pulsed-field gel electrophoresis (PFGE) and ribotyping along with
      antimicrobial susceptibility testing. RESULTS: Seventy six Vibrio cholerae O1
      strains from different geographical areas were used to represent 2007 to 2010
      cholera epidemics in Kenya. Serotype Inaba was dominant (88.2%) compared to
      Ogawa. The isolates showed varying levels of antibiotic resistance ranging from
      100% susceptible to tetracycline, doxycycline, ofloxacin, azithromycin,
      norfloxacin and ceftriaxone to 100% resistant to furazolidone, trimethoprim
      sulfamethoxazole, polymyxin-B and streptomycin. The isolates were positive for
      ctxA, tcpA (El Tor), rtxC genes and were biotype El Tor variant harboring
      classical ctxB gene. All the isolates were classified as cholera toxin (CT)
      genotype 1 as they had mutation in the ctxB at positions 39 and 68. All the
      isolates had genetically similar NotI PFGE and BglI ribotype patterns. The
      absence of any observed variation is consistent with a clonal origin for all of
      the isolates. CONCLUSION: Kenya experienced cholera numerous outbreak from 2007
      2010. The clinical Vibrio cholerae O1 isolates from the recent cholera epidemic
      were serotypes Inaba and Ogawa, Inaba being the predominant serotype. The Vibrio
      cholerae O1 strains were biotype El Tor variants that produce cholera toxin B
      (ctx B) of the classical type and were positive for ctxA, tcpA El Tor and rtxC
      genes.

PMID- 25584123
TI  - [Thrombocytosis in a macrophage activation syndrome complicating systemic lupus
      erythematosus].

PMID- 25584124
TI  - [Distal radioulnar conflict revealing aneurysmal bone cyst].

PMID- 25584122
TI  - [High prevalence of burnout in the Tunisian units that support terminally ill
      patients].

PMID- 25584125
TI  - Sub-specialization in plastic surgery in sub-Saharan Africa: capacities, gaps and
      opportunities.
AB  - The skill set of a plastic surgeon, which addresses a broad range of soft tissue
      conditions that are prevalent in sub-Saharan Africa, remains relevant in the
      unmet need for surgical care. Recently, there has being a major paradigm shift
      from discipline-based to disease-based care, resulting in an emerging component
      of patient-centered care; adequate access to subspecialty care in plastic and
      reconstructive surgery. Given the need for an evolution in sub-specialization,
      this article focuses on the benefits and future role of differentiation of
      plastic surgeons into sub-specialty training pathways in sub-Saharan Africa. 

PMID- 25584127
TI  - Asymptomatic Dandy-Walker syndrome in an adult.

PMID- 25584128
TI  - Primary lymphedema tarda.

PMID- 25584126
TI  - [Recurrent meningitis revealing Behcet disease: report of two cases].

PMID- 25584129
TI  - [Lost to follow-up in radiotherapy: experience of the National Institute of
      Oncology in Morocco].

PMID- 25584130
TI  - [A rare case of malignant hemangiopericytoma of the lower limb].

PMID- 25584131
TI  - [Massive hydatid pulmonary embolism].

PMID- 25584132
TI  - A rare cause of intestinal obstruction: ileosigmoid knot.
AB  - Intestinal obstruction is common surgical emergency; ileosigmoid knot is a rare
      cause of intestinal obstruction (a loop ileum and sigmoid colon twisted around
      each other in a knot). We recorded a three cases in HASSAN II hospital in the
      last 3 years. 

PMID- 25584133
TI  - Assessment of a Diagnostic Predictive Probability Model Provided by a
      Multispectral Digital Skin Lesion Analysis Device for Melanoma and Other High
      risk Pigmented Lesions and its Impact on Biopsy Decisions.
AB  - OBJECTIVE: Risk prediction models for primary malignant melanoma thus far have
      relied on qualitative patient information. The authors propose a quantitative
      diagnostic predictive probability model using Multispectral Digital Skin Lesion
      Analysis for melanoma and other high-risk pigmented lesions and evaluate its
      effectiveness optimizing biopsy decisions by dermatologists. DESIGN: Data from
      1,632 pigmented lesions analyzed by a Multispectral Digital Skin Lesion Analysis
      device were used to perform a logistic regression analysis. This new quantitative
      melanoma or melanoma/atypical melanocytic hyperplasia/high-grade dysplastic nevus
      probability model was then evaluated to determine its impact on dermatologist
      decisions to biopsy pigmented lesions clinically suggestive of melanoma.
      Participants were given an electronic keypad and answered "yes" or "no" if they
      would biopsy each of 12 pigmented lesions when presented first with patient
      history, clinical images, and dermoscopic images and again when subsequently
      shown Multispectral Digital Skin Lesion Analysis data. SETTING/PARTICIPANTS:
      Study of 191 dermatologists at a medical conference. MEASUREMENTS: Sensitivity,
      specificity, biopsy accuracy, overall biopsy rate, and percentage dermatologists
      biopsying all five melanomas. RESULTS: Dermatologists were significantly more
      sensitive, specific, and accurate while decreasing overall biopsy rates with
      Multispectral Digital Skin Lesion Analysis probability information. CONCLUSION:
      Integration of Multispectral Digital Skin Lesion Analysis probability information
      in the biopsy evaluation and selection process of pigmented lesions has the
      potential to improve melanoma sensitivity of dermatologists without the
      concomitant costs associated with additional biopsies being performed.

PMID- 25584134
TI  - Tolerability and Pharmacokinetics of Ingenol Mebutate 0.05% Gel Applied to
      Treatment Areas up to 100cm(2) on the Forearm(s) of Patients with Actinic
      Keratosis.
AB  - OBJECTIVE: To determine safety, tolerability, and systemic absorption of ingenol
      mebutate 0.05% gel applied for two consecutive days to treatment areas up to
      100cm(2) on the forearm(s) of patients with actinic keratosis. DESIGN AND
      SETTING: Two studies are reported: a Phase 1, multicenter, open-label, dose-area
      escalation cohort study (http://www.clinicaltrials.gov/ct2/show/NCT00659893) and
      a Phase 2, double-blind, vehicle-controlled pharmacokinetic study
      (http://clinical trials.gov/ct2/show/NCT00852137). PARTICIPANTS: The Phase 1
      study included male patients (n=65), mean age 68.1 years; the Phase 2 study
      included both male and female patients (n=16), mean age 63.3 years. MEASUREMENTS:
      In the Phase 1 study, patients assigned to escalating dose-area cohorts were
      evaluated for local skin responses, adverse events, and any other relevant safety
      data. In the pharmacokinetic study, blood samples were collected pre-dose and for
      up to 24 hours after administration on Day 2, and analyzed for ingenol mebutate
      and its primary metabolites. In both studies, safety assessments were performed
      on Days 2, 3, 8, 15, 29, and 57 (study end). RESULTS: In the Phase 1 study, most
      adverse events were mild, and all treatment-related adverse events resolved
      before the end of the study. The 100cm(2) treatment area showed a small increase
      in the overall intensity of mean composite local skin response scores. There was
      no quantifiable systemic exposure to ingenol mebutate or its primary metabolites.
      CONCLUSION: Ingenol mebutate 0.05% gel has a good safety profile when applied to
      treatment areas up to 100cm(2) with acceptable tolerability and local skin
      responses. There is no systemic absorption following application to areas of
      100cm(2).

PMID- 25584135
TI  - Efficacy, Safety, and Out-of-pocket Costs are the Most Important Factors to
      Patients in Choosing a Psoriasis Therapy.
AB  - OBJECTIVE: To determine which factors (i.e., cost, efficacy, safety, and method
      of delivery) influence choice of psoriasis treatment by patients and how patients
      obtain information regarding treatment options. DESIGN: Anonymous survey.
      SETTING: Specialty Psoriasis Clinic at an academic dermatology department over a
      six-month period. PARTICIPANTS: Convenience sample of 40 psoriasis patients.
      MEASUREMENTS: Participant demographics, psoriasis treatment history, sources of
      information about treatment options, factors influencing treatment choices, and
      knowledge of treatment costs. RESULTS: The mean (+/-SD) patient age and duration
      of psoriasis was 50 (+/-17) and 19 (+/-17) years, respectively. Factors
      influencing patient's choice of psoriasis treatment were, in order of importance:
      efficacy (90% very important), safety/side effects (65%), patient's own cost
      (53%), then total treatment cost (46%), frequency of use (37%), and method of
      medication delivery (i.e., topical, oral, or injection; 17%). Eighty percent of
      patients reported not knowing the total cost of any psoriasis treatments. The
      patient's dermatologist was identified as both the most important (90%) and the
      most influential (75%) source of information for selecting psoriasis treatments,
      with the internet being the second most important source. CONCLUSION: Patients,
      in large measure, are unaware of the costs for different psoriasis treatments.
      Efficacy, safety, and out-of-pocket costs are the most important factors to
      patients in deciding on a psoriasis treatment.

PMID- 25584136
TI  - Radiation-induced Breast Telangiectasias Treated with the Pulsed Dye Laser.
AB  - BACKGROUND AND OBJECTIVES: Radiation dermatitis is a frequent sequela of adjuvant
      radiation therapy for breast cancer. Clinical manifestations include prominent
      telangiectasias that may be physically disfiguring and psychologically
      distressing for the patient. The objective of this study was to review cases of
      breast cancer patients with radiation-induced breast telangiectasias treated with
      the pulsed dye laser and assess clinical efficacy. The patient's perception of
      treatment was also reviewed. STUDY DESIGN: A retrospective chart review of
      patients treated for radiation-induced telangiectasias was conducted at the
      Dermatology Division of Memorial Sloan-Kettering Cancer Center. MATERIALS AND
      METHODS: Pre- and post-clinical photos were used to assess clearance by two
      independent raters. Patient's comments were assessed from visit notes and the
      treating physicians for the impact of treatment on the patient's overall well
      being. RESULTS: All patients (n=11) experienced clinical improvement in the
      radiation-induced telangiectasias. The mean number of treatments was 4.3 (2-9)
      with an average fluence of 4.2J/cm(2) (585nm platform) and 7.8J/cm(2) (595nm) (4
      8 J/cm(2)) used. The mean percent clearance was 72.7 percent (50-90%). Adverse
      effects were not encountered including those with breast implants or flap
      reconstruction. Patients reported an improvement in their well-being, including
      an improved sense of confidence. LIMITATIONS: LIMITATIONS include the small
      sample size, nonstandardized digital images, and nonsystematic collection of
      patient-reported outcomes. CONCLUSION: The pulsed dye laser is an efficacious
      treatment for radiation-induced breast telangiectasias. Multiple treatments are
      required for greater than 50-percent clearance and conservative treatment
      parameters are advised. Patients also reported an improved quality of life.

PMID- 25584137
TI  - Autologous therapies in dermatology.
AB  - Autologous therapy is a therapeutic intervention that uses an individual's cells
      or tissues, which are processed outside the body, and reintroduced into the
      donor. This emerging field presently represents a mere tip of the iceberg with
      much knowledge and applications yet to be discovered. It, being free from risks
      of hypersensitivity reactions and transmission of infectious agents, has been
      explored in various fields, such as plastic surgery, orthopedics, and
      dermatology. This review article focuses on various forms of autologous therapies
      used in dermatology along with their applications and mechanisms of action. 

PMID- 25584138
TI  - A review of epidermal maturation arrest: a unique entity or another description
      of persistent granulation tissue?
AB  - OBJECTIVE: To conduct a review of reported cases of epidermal maturation arrest
      and to compare their clinical and histological descriptions with that of
      persistent granulation tissue with a focus on diagnostic methods and response to
      treatment. METHODS: The authors performed a literature search within Pubmed,
      Embase, Google Scholar, and Web of Science for all reported cases of epidermal
      maturation arrest under the terms "epidermal maturation arrest," "epidermal
      arrest," "epidermal maturation," and "re-epithelialization maturation arrest."
      They reviewed the clinical and histological presentation of hypergranulation
      tissue as well as the evidence for the most widely used treatments. RESULTS:
      There is only one case series and one case report of epidermal maturation arrest,
      and the former gives the most detailed clinical and histological description
      including response to treatment. The clinical description, histological findings,
      and response to treatment of all cases are comparable to that of persistent
      granulation tissue and there is no histological or cytological data provided to
      support that epidermal maturation arrest exists as a distinct entity. CONCLUSION:
      Among the cases of epidermal maturation arrest reported in the literature, there
      is insufficient evidence that keratinocytes acquired a state of arrest in their
      migration. Rather, the described cases appear to have been complicated by
      persistent granulation tissue, a well-known aberration in wound healing.

PMID- 25584139
TI  - Persistent sexual dysfunction and depression in finasteride users for male
      pattern hair loss: a serious concern or red herring?
AB  - The use of finasteride for the treatment of male pattern hair loss has recently
      been the focus of media and internet attention for potential irreversible sexual
      dysfunction and severe depression. The purpose of this study was to perform a
      critical review of the recent studies reporting prolonged sexual dysfunction and
      depression with the use of finasteride for the treatment of male pattern hair
      loss. A literature search was performed using PubMed to review the literature
      pertaining to any potential adverse effects with the use of finasteride and its
      treatment of male pattern hair loss. The authors conclude that the reports of
      potential irreversible sexual dysfunction and severe depression do raise concerns
      about the safety of finasteride; however, these studies are wrought with
      significant bias. Therefore, larger, randomized, double blind, controlled trials
      are warranted to further ascertain the true potential risks or confirm long-term
      safety profile of finasteride use. 

PMID- 25584140
TI  - Non-contiguous finished genome sequence and description of the gliding bacterium
      Flavobacterium seoulense sp. nov.
AB  - Flavobacterium seoulense strain EM1321(T) is the type strain of Flavobacterium
      seoulense sp. nov., a proposed novel species within the genus Flavobacterium.
      This strain is a Gram-reaction-negative, aerobic, rod-shaped bacterium isolated
      from stream water in Bukhansan National Park, Seoul. This organism is motile by
      gliding. Here, we describe the features of Flavobacterium seoulense EM1321(T),
      together with its genome sequence and annotation. The genome comprised 3,792,640
      bp, with 3,230 protein-coding genes and 52 RNA genes. 

PMID- 25584142
TI  - Mitochondrial DNA somatic mutation in cancer.
AB  - Cancer cells are known to drastically alter cellular energy metabolism. The
      Warburg effect has been known for over 80 years as pertaining cancer-specific
      aerobic glycolysis. As underlying molecular mechanisms are elucidated so that
      cancer cells alter the cellular energy metabolism for their advantage, the
      significance of the modulation of metabolic profiles is gaining attention. Now,
      metabolic reprogramming is becoming an emerging hallmark of cancer. Therapeutic
      agents that target cancer energy metabolism are under intensive investigation,
      but these investigations are mostly focused on the cytosolic glycolytic
      processes. Although mitochondrial oxidative phosphorylation is an integral part
      of cellular energy metabolism, until recently, it has been regarded as an
      auxiliary to cytosolic glycolytic processes in cancer energy metabolism. In this
      review, we will discuss the importance of mitochondrial respiration in the
      metabolic reprogramming of cancer, in addition to discussing the justification
      for using mitochondrial DNA somatic mutation as metabolic determinants for cancer
      sensitivity in glucose limitation. 

PMID- 25584141
TI  - A panoramic overview of mitochondria and mitochondrial redox biology.
AB  - Mitochondria dysfunction was first described in the 1960s. However, the extent
      and mechanisms of mitochondria dysfunction's role in cellular physiology and
      pathology has only recently begun to be appreciated. To adequately evaluate
      mitochondria-mediated toxicity, it is not only necessary to understand
      mitochondria biology, but discerning mitochondrial redox biology is also
      essential. The latter is intricately tied to mitochondrial bioenergetics.
      Mitochondrial free radicals, antioxidants, and antioxidant enzymes are players in
      mitochondrial redox biology. This review will provide an across-the-board, albeit
      not in-depth, overview of mitochondria biology and mitochondrial redox biology.
      With accumulating knowledge on mitochondria biology and mitochondrial redox
      biology, we may devise experimental methods with adequate sensitivity and
      specificity to evaluate mitochondrial toxicity, especially in vivo in living
      organisms, in the near future. 

PMID- 25584144
TI  - Comparison of international guidelines of dermal absorption tests used in
      pesticides exposure assessment for operators.
AB  - The number of farmers who have suffered from non-fatal acute pesticide poisoning
      has been reported to vary from 5.7% to 86.7% in South Korea since 1975.
      Absorption through the skin is the main route of exposure to pesticides for
      farmers who operate with them. Several in vitro tests using the skins of humans
      or animal and in vivo tests using laboratory animals are introduced for the
      assessment of human dermal absorption level of pesticides. The objective of this
      study is to evaluate and compare international guidelines and strategies of
      dermal absorption assessments and to propose unique approaches for applications
      into pesticide registration process in our situation. Until present in our
      situation, pesticide exposure level to operator is determined just using default
      value of 10 as for skin absorption ratio because of data shortage. Dermal
      absorption tests are requested to get exposure level of pesticides and to
      ultimately know the safety of pesticides for operators through the comparison
      with the value of AOEL. When the exposure level is higher than AOEL, the
      pesticide cannot be approved. We reviewed the skin absorption test guidelines
      recommended by OECD, EFSA and EPA. The EPA recommends assessment of skin
      absorption of pesticides for humans through the TPA which includes all the
      results of in vitro human and animal and animal in vivo skin absorption studies.
      OECD and EFSA, employ a tiered approach, which the requirement of further study
      depends on the results of the former stage study. OECD guidelines accept the
      analysis of pesticide level absorbed through skin without radioisotope when the
      recovery using the non-labeled method is within 80~120%. Various factors are
      reviewed in this study, including the origin of skin (gender, animal species and
      sites of skin), thickness, temperature and, etc., which can influence the
      integrity of results. 

PMID- 25584143
TI  - Mitophagy: therapeutic potentials for liver disease and beyond.
AB  - Mitochondrial integrity is critical for maintaining proper cellular functions. A
      key aspect of regulating mitochondrial homeostasis is removing damaged
      mitochondria through autophagy, a process called mitophagy. Autophagy dysfunction
      in various disease states can inactivate mitophagy and cause cell death, and
      defects in mitophagy are becoming increasingly recognized in a wide range of
      diseases from liver injuries to neurodegenerative diseases. Here we highlight our
      current knowledge on the mechanisms of mitophagy, and discuss how alterations in
      mitophagy contribute to disease pathogenesis. We also discuss mitochondrial
      dynamics and potential interactions between mitochondrial fusion, fission and
      mitophagy. 

PMID- 25584145
TI  - Transformation of Mouse Liver Cells by Methylcholanthrene Leads to Phenotypic
      Changes Associated with Epithelial-mesenchymal Transition.
AB  - Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) have
      been implicated in cancer development and progression. However, the effects of
      PAHs on carcinogenesis are still poorly understood. Here, we characterized a
      mouse cancer cell line BNL 1ME A. 7R.1 (1MEA) derived by transformation of non
      tumorigenic liver cell line BNL CL.2 (BNL) using 3-methylcholanthrene (3MC), a
      carcinogenic PAH. RT-PCR and immunoblot analysis were used to determine the
      expression level of mRNA and proteins, respectively. To determine functionality,
      cell motility was assessed in vitro using a transwell migration assay. Both mRNA
      and protein levels of E-cadherin were significantly decreased in 1MEA cells in
      comparison with BNL cells. While the expression levels of mesenchymal markers and
      related transcription factors were enhanced in 1MEA cells, which could lead to
      increase in cell motility. Indeed, we found that 7-day exposure of BNL cells to 3
      MC reduced the level of the adhesion molecule and epithelial marker Ecadherin and
      increased reciprocally the level of the mesenchymal marker vimentin in a dose
      dependent manner. Taken together, these results indicate that the process of
      epithelial-mesenchymal transition (EMT) may be activated during premalignant
      transformation induced by 3-MC. A mechanism study to elucidate the relation
      between 3-MC exposure and EMT is underway in our laboratory. 

PMID- 25584146
TI  - Influence of lead on repetitive behavior and dopamine metabolism in a mouse model
      of iron overload.
AB  - Exposures to lead (Pb) are associated with neurological problems including
      psychiatric disorders and impaired learning and memory. Pb can be absorbed by
      iron transporters, which are up-regulated in hereditary hemochromatosis, an iron
      overload disorder in which increased iron deposition in various parenchymal
      organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe)
      gene is the major cause of hemochromatosis, the transport and toxicity of Pb in
      Hfe-related hemochromatosis are largely unknown. To elucidate the relationship
      between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild
      type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6
      weeks and examined for behavioral phenotypes using the nestlet-shredding and
      marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice
      was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb
      exposure did not alter shredding latency in Hfe-mutant mice. In the marble
      burying test, Hfe-mutant mice showed an increased number of marbles buried
      compared with wild-type mice (p = 0.002), indicating more repetitive behavior
      upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles
      than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant
      mice did not change whether or not exposed to Pb. These results suggest that Hfe
      mutation could normalize Pb-induced behavioral alteration. To explore the
      mechanism of repetitive behavior caused by Pb, western blot analysis was
      conducted for proteins involved in brain dopamine metabolism. The levels of
      tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both
      genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine
      transporter and dopamine D1 receptor with D2 receptor elevated. Taken together,
      our data support the idea that both Pb exposure and Hfe mutation increase
      repetitive behavior in mice and further suggest that these behavioral changes
      could be associated with altered dopaminergic neurotransmission, providing a
      therapeutic basis for psychiatric disorders caused by Pb toxicity. 

PMID- 25584147
TI  - Immune Modulation of B. terrestris Worker (a Type of Bumblebee), Extract on CFA
      induced Paw Edema in Rats.
AB  - To develop a composition for enhancing immunity, based on alcohol extracts of the
      bumblebee as an active ingredient, bumblebee ethanol extracts were evaluated for
      their protective effect in chronic models of inflammation, adjuvant induced rat
      arthritis. B. terrestris worker extract (SDIEX) and, B. hypocrita sapporoensis
      lava an pupa extract (SPDYBEX), significantly decreased paw edema in arthritic
      rats, at a dose 100 mg/kg, respectively. The cytokine levels related inflammation
      of COX-2, sPLA2, VEGF, and TNF-alpha, were decreased, compared to positive
      control, indomethacin (5 mg/kg). Histopathological data demonstrated decreases
      inflammatory activity, hind paw edema, and repaired hyaline articular cartilage
      in DRG over a 2 wk administration. HPLC and GC-MS analysis of SDIEX and SPDYBEX
      revealed the presence of cantharidin. 

PMID- 25584148
TI  - Anti-wrinkle Effects of Water Extracts of Teas in Hairless Mouse.
AB  - Tea flavonoids and polyphenols are well known for their extraordinary antioxidant
      activity which is considered important for anti-aging processes in animals. This
      study evaluated the anti-wrinkle effects of three different kinds of tea
      (Camellia sinensis) water extracts (CSWEs) including green, white, and black teas
      using a photoaged hairless mouse model. Data showed that the CSWE-treatment
      greatly improved skin conditions of mice suffering from UVB-induced photoaging,
      based on the parameters including the skin erythema index, moisture capacity, and
      transepidermal water loss. In addition, the wrinkle measurement and image
      analysis of skin replicas indicated that CSWEs remarkably inhibited wrinkle
      formation. In histological examination, the CSWE-treated mice exhibited
      diminished epidermal thickness and increased collagen and elastic fiber content,
      key signatures for skin restoration. Furthermore, the reduced expression of MMP
      3, a collagen-degradative enzyme, was observed in the skin of CSWE-treated
      animals. Interestingly, comparative data between green, white, and black tea
      indicated that the anti-wrinkle activity of white tea and black tea is equally
      greater than that of green tea. Taken together, these data clearly demonstrated
      that CSWEs could be used as an effective anti-wrinkle agent in photoaged animal
      skin, implying their extended uses in therapeutics. 

PMID- 25584149
TI  - Protection of Saururus Chinensis Extract against Liver Oxidative Stress in Rats
      of Triton WR-1339-induced Hyperlipidemia.
AB  - Saururus chinensis has been reported to contain compounds such as lignans,
      alkaloids, diterpenes, flavonoids, tannins, steroids, and lipids. Fermentation is
      commonly used to break down certain undesirable compounds, to induce effective
      microbial conversion, and to improve the potential nutraceutical values. Previous
      studies have reported that the fermentation process could modify naturally
      occurring constituents, including isoflavons, saponins, phytosterols, and
      phenols, and could enhance biological activities, specifically antioxidant and
      antimicrobial properties. The probiotic strains used for fermentation exert
      beneficial effects and are safe. In this study, the antioxidative effects of the
      Bacillus subtilis fermentation of Saururus chinensis were investigated in a rat
      model with Triton WR-1339-induced hyperlipidemia by comparing the measured
      antioxidative biological parameters of fermented Saururus chinensis extract to
      those of nonfermented Saururus chinensis extract. Fermentation played a more
      excellent role than nonfermentation in ultimately protecting the body from
      oxidative stress in the liver of the experimental rats with Triton WR-1339
      induced hyperlipidemia. 

PMID- 25584150
TI  - Peppermint Oil Promotes Hair Growth without Toxic Signs.
AB  - Peppermint (Mentha piperita) is a plant native to Europe and has been widely used
      as a carminative and gastric stimulant worldwide. This plant also has been used
      in cosmetic formulations as a fragrance component and skin conditioning agent.
      This study investigated the effect of peppermint oil on hair growth in C57BL/6
      mice. The animals were randomized into 4 groups based on different topical
      applications: saline (SA), jojoba oil (JO), 3% minoxidil (MXD), and 3% peppermint
      oil (PEO). The hair growth effects of the 4-week topical applications were
      evaluated in terms of hair growth, histological analysis, enzymatic activity of
      alkaline phosphatase (ALP), and gene expression of insulin-like growth factor-1
      (IGF-1), known bio-markers for the enhanced hair growth. Of the 4 experimental
      groups, PEO group showed the most prominent hair growth effects; a significant
      increase in dermal thickness, follicle number, and follicle depth. ALP activity
      and IGF-1 expression also significantly increased in PEO group. Body weight gain
      and food efficiency were not significantly different between groups. These
      results suggest that PEO induces a rapid anagen stage and could be used for a
      practical agent for hair growth without change of body weight gain and food
      efficiency. 

PMID- 25584151
TI  - Variation of nephrotoxicity biomarkers by urinary storage condition in rats.
AB  - Recently, there has been an increase in the use of several nephrotoxicity
      biomarkers in preclinical experiments. In addition, it has been indicated that
      the result may have been influenced by secondary factors, such as sample storage
      condition or storage period. In this study, we have assessed the variation in
      urinary nephrotoxicity biomarkers as a result of urine storage conditions and
      storage period of the urine. Urine was sampled from specific pathogen-free
      Sprague-Dawley rats (19 weeks old), which were housed individually in hanged
      stainless steel wire mesh cages. Urine was stored at 20C, at 4C, or at -70C after
      sampling. The levels of the biomarkers such as beta-2 microglobulin (B2M),
      cystatin-C (Cys-C), N-acetyl-beta- D-glucosaminidase (NAG), micro albumin (MA),
      micro protein (MP) were measured at 6, 24, 48 and 144 hr after sampling. The B2M
      level was significantly decreased at 6, 24, 48, and 144 hr compared to 0 hr at 
      70C (p < 0.05, p < 0.01, p < 0.05, and p < 0.05, respectively) and 24 and 144 hr
      at 20C (p < 0.01, p < 0.01, respectively). The Cys-C level was significantly
      decreased at 144 hr compared to 0 hr at 4C (p < 0.01), at 20C (p < 0.05) and at
      70C (p < 0.01). MP and MA levels were not different for 144 hr in all storage
      conditions. Taken together, B2M and Cys-C levels were modulated by storage
      temperature and period. For the enhancement of test accuracy, it is suggested
      that strict protocols be established for samples to minimize the effects of the
      storage conditions on the detected levels of biomarkers. 

PMID- 25584152
TI  - Real-time Detection of Trace Copper in Brain and Kidney of Fish for Medical
      Diagnosis.
AB  - For the detection of trace copper to be used in medical diagnosis, a sensitive
      handmade carbon nanotube paste electrode (PE) was developed using voltammetry.
      Analytical optimized conditions were found at 0.05 V anodic peak current. In the
      same conditions, various common electrodes were compared using stripping
      voltammetry, and the PE was found to be more sharply sensitive than other common
      electrodes. At optimum conditions, the working ranges of 3~19 MUgL(-1) were
      obtained. The relative standard deviation of 70.0 MUgL(-1) was determined to be
      0.117% (n = 15), and the detection limit (S/N) was found to be 0.6 MUgL(-1) (9.4
      * 10(-9) M). The results were applied in detecting copper traces in the kidney
      and the brain cells of fish. 

PMID- 25584153
TI  - Ebola: are we prepared for recurring infectious threats?

PMID- 25584155
TI  - Obstetric and perinatal outcomes of teenage pregnant women attending a tertiary
      teaching hospital in oman.
AB  - OBJECTIVE: To study the obstetrical and perinatal outcomes of teenage Omani girls
      with singleton pregnancies at a tertiary teaching hospital. METHODS: This is a
      retrospective case control study. We reviewed obstetric and perinatal outcomes of
      teenage nulliparous pregnant Omani girls with singleton pregnancies aged 14 to 19
      years, delivered at Sultan Qaboos University Hospital, between 1 July 2006 and 30
      June 2013. We compared their outcomes with outcomes of pregnant nulliparous Omani
      women with singleton pregnancies aged 20 to 25 years old delivered at the same
      hospital during the same period. RESULTS: When compared with pregnant women
      (n=307), teenage pregnant girls (n=307) were found to have higher proportion of
      preterm delivery <32 weeks (7% vs. 3%, p=0.040), preterm pre-labor rupture of
      membranes (PPROM) (19% vs. 11%, p=0.005) and anemia (58% vs. 44%, p=0.005).
      Cesarean section rate was higher in women than teenager girls (20% vs. 10%,
      p=0.001). Teenager girls had lighter babies (mean weight +/- standard deviation
      2,750+/-690 vs. 2,890+/-480, p=0.020), incidence of very low birth weight babies
      (<1,500g) was higher in teenagers (3.9% vs. 0.3%, p=0.003), but perinatal
      mortality rate was similar in the two groups. CONCLUSION: Teenage pregnant Omani
      women are at increased risk of preterm delivery before 32 weeks gestation, PPROM,
      anemia, and delivering very low birth weight babies.

PMID- 25584154
TI  - Starvation based differential chemotherapy: ?a novel approach for cancer
      treatment.
AB  - Cancer patients undergoing chemotherapy treatment are advised to increase food
      intake to overcome the therapy-induced side effects, and weight loss. Dietary
      restriction is known to slow down the aging process and hence reduce age-related
      diseases such as cancer. Fasting or short-term starvation is more effective than
      dietary restriction to prevent cancer growth since starved cells switch off
      signals for growth and reproduction and enter a protective mode, while cancer
      cells, being mutated, are not sensitized by any external growth signals and are
      not protected against any stress. This phenomenon is known as differential stress
      resistance (DSR). Nutrient signaling pathways involving growth hormone/insulin
      like growth factor-1 axis and its downstream effectors, play a key role in DSR in
      response to starvation controlling the other cell maintenance systems, such as
      autophagy and apoptosis, that are related to the tumorigenesis. Yeast cells
      lacking these effectors are better protected against oxidative stress compared to
      normal cells. In the same way, starvation protects many cell lines and mice
      against high-dose chemotherapeutic drugs. According to a series of studies,
      fasting results in overall reduction in chemotherapy side effects in cancer
      patients. Data shows that starvation-dependent differential chemotherapy is safe,
      feasible and effective in cancer treatment, but the possible side effects of
      starvation limit its efficacy. However, further studies and clinical trials may
      result in its implementation in cancer treatment. 

PMID- 25584156
TI  - Are tubes containing sodium fluoride still needed for the measurement of blood
      glucose in hospital laboratory practice?
AB  - OBJECTIVES: To compare glucose values obtained using sodium flouride (NaF) tubes
      and serum separation tubes (SST) in a tertiary care hospital laboratory setting.
      METHODS: This study was conducted at the Clinical Biochemistry Laboratory, Royal
      Hospital, Oman. During the study period (1 September-30 November 2013), 50 pairs
      (one NaF tube and one SST) of patient's blood specimens were randomly collected.
      Following separation of plasma (NaF tubes) and serum (SST), glucose
      concentrations were measured by hexokinase assay using the Architect c8000.
      Fifteen pairs of these tubes were kept in the refrigerator at 4 degrees C and
      plasma/serum glucose concentrations were measured daily up to seven days after
      collection. RESULTS: Comparing plasma (NaF) and serum (SST) results of glucose
      values (n=50) showed an average difference of 0.00mmol/L (range -0.60 to
      +0.60mmol/L). Bland Altman analysis gave a non-significant constant bias of 0.10
      +/-0.195mmol/L (bias +/-SD). Pearson correlation between plasma (NaF) and serum
      (SST) glucose concentrations revealed a significant correlation approaching unity
      with r(2)= 0.9991. No significant differences in glucose values were noted for
      both plasma and serum in 15 pairs of NaF and SST tubes when analyzed seven days
      following refrigeration. Hemolysis was observed in five (10%) NaF tubes compared
      with two (4%) SST. CONCLUSION: There is no difference in glucose values collected
      from plasma NaF tubes or serum SST, and so SST can be used in hospital laboratory
      settings as there are practical advantages, including cost-effectiveness and
      reduction in blood volume drawn when utilizing these tubes for glucose and other
      tests from a single blood collection tube.

PMID- 25584157
TI  - What do Omani Women know about Breast Cancer Symptoms?
AB  - OBJECTIVES: Breast cancer is one of the most common cancers and a leading cause
      of cancer-related mortality in women worldwide. Studies to detect the awareness
      of breast cancer among Arab women are few and point to a lack of breast cancer
      knowledge among females. Early detection of breast cancer plays a leading role in
      reducing mortality rates and improving prognosis. This study aims to assess the
      knowledge and awareness of breast cancer symptoms among Omani women. METHODS: A
      descriptive, cross-sectional survey design was carried out in Muscat, Oman. The
      study was conducted at three health centers and three shopping malls using
      convenience sampling. A total of 369 women consented to be part of the study and
      completed a questionnaire. Responses to the questionnaire were summed to give an
      overall knowledge score. Descriptive statistics were used to summarize the data,
      which was also analyzed statistically. RESULTS: Among the total number of women
      68 (19%) were calculated to have poor knowledge, 219 (59%) had average knowledge,
      77 (21%) had good knowledge, and five (1%) had excellent knowledge on breast
      cancer. Among the variables, education status (p=0.002, p<0.050), and family
      history of breast cancer (p =0.000, p<0.010) was significantly related to a
      higher knowledge level. CONCLUSION: The study revealed that there was lack of
      awareness and knowledge on breast cancer symptoms among Omani women. Breast
      cancer awareness and early detection through regular breast screening is
      important to reduce the mortality and morbidity of the disease.

PMID- 25584158
TI  - Allergic rhinitis and associated comorbidities: prevalence in oman with knowledge
      gaps in literature.
AB  - OBJECTIVES: Allergic rhinitis (AR) is a global health problem and its impact on
      health related quality of life for patients is substantial, and the economic
      impact often underestimated. The prevalence of allergic rhinitis in Oman is
      unknown. This study aimed to estimate the prevalence of AR and associated co
      morbidities among adults in Oman. Its secondary objective was to identify
      knowledge gaps in the literature with the aim of directing future research.
      METHODS: A prospective, cross-sectional study of patients who presented to the
      outpatient otolaryngology clinic at Sultan Qaboos University Hospital with nasal
      symptoms between June 2010 and June 2011 was conducted. RESULTS: A total of 887
      patients were seen with nasal complaints. Among them 127 patients were diagnosed
      with non-infective rhinitis, the mean age of presentation was 27 years. AR was
      noted in 48% of patients, and non-allergic rhinitis in 52%. The prevalence of AR
      was 7%, with females being more affected than males, and age ranging from 18 to
      51 years. Prevalence of perennial AR was 84% compared to seasonal AR which was
      16%. The most common perennial antigens were house dust mites (80%) followed by
      cockroaches (67%). All patients diagnosed with seasonal AR were found to be
      sensitive to Russian thistle. The prevalence of chronic rhinosinusitis in
      patients with AR was 34%. CONCLUSION: The prevalence of AR in the adult
      population presenting with nasal symptoms was found to be 7%, with associated
      chronic rhinosinusitis present in a third of these patients. However, there
      appears to be substantial knowledge gaps regarding the association of other
      comorbidities, like otitis media, bronchitis and bronchial asthma, the long-term
      outcomes of medical management, and indication of surgical intervention in
      patients with AR. Future research in AR among Omani patients should aim to
      address these issues.

PMID- 25584159
TI  - Clinical presentation, management, and outcome of patients with incidental renal
      angiomyolipoma in qatar.
AB  - OBJECTIVES: Our study aimed to analyze the clinical presentation, management, and
      outcome of renal angiomyolipoma patients incidentally detected upon computed
      tomography (CT) examination. METHODS: Between 2004 and 2008, all patients who
      underwent abdominal CT examination for any reason at the radiology department at
      Hamad General Hospital, Qatar were retrospectively reviewed. The diagnosis of
      renal angiomyolipoma was based on abdominal CT evaluation. Angiomyolipoma
      patients were followed-up by CT evaluation as per standard care for three years
      to observe any change in size and outcome. RESULTS: A total of 13,115 patients
      were screened, of which 56 (40 females and 16 males) had renal angiomyolipoma.
      The mean age of patients was 52+/-13 years with 46% Qatar nationals. The majority
      (95%) of cases had unilateral tumors (52% right-sided and 43% left-sided). Twenty
      six cases showed increase in tumor size and the median increase was 0.5cm (0.1
      3.6). Surgical intervention was required in four (7%) cases with tumor size
      >=4cm. The overall mortality on follow-up was 7%. The cause of death included
      metastasis, renal failure, hepatic failure and mesenteric thromboembolism.
      CONCLUSION: Renal angiomyolipoma is an uncommon benign tumor with an overall
      prevalence of 0.4% in Qatar. It has characteristic clinical features and its
      recognition is often challenging for proper clinical diagnosis and treatment in
      asymptomatic patients. Asymptomatic patients need regular radiological
      surveillance. In contrast, surgical interventions are mainly required in
      symptomatic patients with increased tumor size (>=4cm). Timely diagnosis and
      treatment is necessary to avoid complications such retroperitoneal hemorrhage and
      renal impairment.

PMID- 25584160
TI  - The Effect of LI4 Acupressure on Labor Pain Intensity and Duration of Labor: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: To evaluate the effect of LI4 acupressure on labor pain and duration
      during the first stage of labor. METHODS: Parturient women (n=149) with singleton
      pregnancies in the active phase of spontaneous labor, without any medical or
      obstetric problems, were enrolled in this single-blinded, randomized, clinical
      trial. Participants were placed into one of three groups: an LI4 acupressure
      group, a touching group, and a control group in which no pharmacological or non
      pharmacological methods of pain relief were used. Pain intensity was measured by
      visual analog scale before and after the intervention in the first stage of
      labor. Pressure or touch was applied for 30 minutes during uterine contractions.
      RESULTS: The difference in the pain scores between the acupressure and control
      group was statistically significant (p<0.001) but there was no statistically
      significant (p=0.942) difference in the duration of the first stage of labor
      between the three groups. CONCLUSION: Acupressure is an effective, non-invasive,
      and easily applicable technique to reduce labor pain.

PMID- 25584161
TI  - Transarterial chemoembolization in unresectable hepatocellular carcinoma with
      portal vein thrombosis: a perspective on survival.
AB  - OBJECTIVE: Portal vein thrombosis is considered a relative contraindication for
      transarterial chemoembolization (TACE) in hepatocellular carcinoma. The purpose
      of our study was to evaluate the efficacy of TACE treatment in patients with
      hepatocellular carcinoma with portal vein (PV) thrombosis. METHODS: From April
      2011 to June 2013, 17 patients with unresectable hepatocellular carcinoma with PV
      thrombosis were studied. Patients were assessed for tumor response by imaging at
      regular intervals and the data compared with the baseline laboratory and imaging
      characteristics obtained before treatment. Univariate analysis was used to assess
      the treatments impact on patient survival. Survival analysis was performed using
      Kaplan-Meier estimations. RESULTS: Overall survival rates at three, six and 12
      months were 82%, 71%, and 47%, respectively, with a median of 10 months. Patients
      in Child-Pugh class A had a median survival of 15 months compared to five months
      for those patients in Child-Pugh class B. The median survival period of patients
      responsive to treatment was 13 months while that of non-responders was five
      months. Patients with ascites at the time of presentation had median survival
      period of six months while those who did not had a median survival period of 13
      months. In univariate analysis, response to chemoembolization (p<0.001), ascites
      (p<0.050) and Child-Pugh class at diagnosis (p<0.050) were found to be
      significant prognostic factors. CONCLUSION: TACE is a promising procedure in
      unresectable hepatocellular carcinoma with PV thrombosis. Response to
      chemoembolization, ascites and Child-Pugh class were the most important
      determining factors of survival.

PMID- 25584164
TI  - First presentation of a case of pulmonary alveolar microlithiasis with
      spontaneous pneumothorax.
AB  - Pulmonary Alveolar Microlithiasis (PAM) is a rare disease of unknown origin. It
      is characterized by the presence of small calculi within the alveolar spaces, and
      has various clinical manifestations. Some patients may be asymptomatic for a long
      period of time with subsequent occurrence of dyspnea, dry cough, chest pain, and
      eventually, respiratory failure. Recurrent spontaneous pneumothorax episodes are
      a late complication of the disease. We report the case of an alveolar
      microlithiasis episode in a 42-year-old male, admitted to Tohid Hospital, Iran,
      whose first clinical presentation was symptoms of pneumothorax. He was admitted
      with sudden onset dyspnea and right-sided pleuretic chest pain. Following
      treatment of pneumothorax after chest tube placement, the pulmonary function
      revealed normal indices, and chest radiograph demonstrated diffuse confluence of
      dense micronodular infiltrate. High-resolution computerized tomography scan
      showed diffuse ground glass attenuation and calcifications along the interlobular
      septa and subpleural regions. Transbronchial lung biopsy confirmed the diagnosis
      of PAM. 

PMID- 25584162
TI  - Psychosocial impact of breast cancer diagnosis among omani women.
AB  - OBJECTIVES: The aim of this study was to explore different psychosocial impacts
      on Omani women diagnosed with breast cancer. METHODS: Semi-structured individual
      interviews were conducted with 19 Omani women diagnosed with breast cancer to
      describe the impact of the disease on their personal and social life. Women were
      recruited from wards and out-patient clinics at the Sultan Qaboos University
      Hospital, Muscat. RESULTS: Four main themes emerged. These were: a) factors
      related to psychological distress of the disease and uncertainty (worry of death,
      interference with work and family responsibilities, searching for hope/cure,
      travelling overseas); b) reactions of family members (shocked, saddened, unity,
      pressure to seek traditional treatments); c) views of society (sympathy,
      isolation, reluctant to disclose information); and d) worries and threats about
      the future (side effects of chemotherapy, spread of the disease, effect on
      offspring). CONCLUSION: Breast cancer diagnosis has several devastating
      psychosocial impacts on women in Oman. Healthcare professionals working with
      women with breast cancer should be aware of the different psychosocial impacts of
      the disease on women's lives. Appropriate measures must be taken by the decision
      makers whenever needed, including enforcing positive views and support of Oman's
      society towards women with breast cancer.

PMID- 25584163
TI  - Recurrent myonecrosis involving adductor muscle group bilaterally: a rare
      complication of ?diabetes mellitus.
AB  - Diabetic myonecrosis is a rare and underdiagnosed complication of long-standing,
      uncontrolled diabetes. It usually occurs in patients with long-standing diabetes
      in the presence of microvascular complications. Thigh muscles are more commonly
      affected and the usual presentation is thigh swelling with or without pain,
      systemic features being rare. Magnetic resonance imaging is the gold standard for
      diagnosis. Most patients recover spontaneously with bed rest, adequate analgesia
      and good glycemic control. We present a case of recurrent myonecrosis of adductor
      muscles of the thigh in a patient with long standing type 2 diabetes mellitus who
      recovered with conservative management. 

PMID- 25584165
TI  - Linear growth arrest without weight gain due to overuse of topical clobetasol.
AB  - Prolonged potent topical glucocorticoid therapy in infants can cause iatrogenic
      Cushing's syndrome. This case highlights the rarity of poor weight gain in
      iatrogenic Cushing's syndrome. A 17-month-old boy was referred to outpatients
      pediatric endocrine clinic for evaluation of growth failure. On presentation his
      weight was 9.7kg (5th percentile) and height was 72cm (-3.6 SD below mean for age
      and sex). Systemic examination revealed grossly moon-like face, hypertrichosis
      and thin skin in the genital area. His mother reported using local clobetasol for
      the previous seven months for his diaper dermatitis. Baseline plasma cortisol was
      low (0.3ng/ml, normal range: 60 to 280ng/ml). During standard dose of synthetic
      adrenocorticotropic hormone test, the peak cortisol level was 0.4ng/ml
      (N>180ng/ml) and was consistent with hypothalamic-pituitary-adrenal axis
      suppression. The patient's clinical presentation and laboratory investigations
      confirmed the diagnosis of secondary adrenal insufficiency and iatrogenic
      Cushing's syndrome. He was treated successfully by discontinuing use of
      clobetasol. His appearance and growth returned to normal within two months.
      Morning cortisol was 101.2ng/ml after stopping the oral physiologic dose of
      hydrocortisone. Our case differed from other reports of iatrogenic Cushing's
      syndrome by presenting in poor weight gain rather than obesity. 

PMID- 25584166
TI  - An Unusual Cause for Sister Mary Joseph's Nodule: A Case Report.
AB  - Sister Mary Joseph's nodule refers to palpable nodules bulging into the umbilicus
      as a result of metastasis from malignancy in the abdomen or pelvis. The most
      common primaries are in the gastrointestinal or genital tract, while other
      origins are considered rare. We recently treated a 71-year-old man who presented
      with painless umbilical swelling. Further investigation, including laboratory,
      radiological and histopathological exam, confirmed the diagnosis of a metastatic
      neuroendocrine tumor. The peculiarity of this case is that the umbilical swelling
      was the initial presentation of a neuroendocrine tumor and, to our knowledge,
      this is the first to be reported. This case demonstrates that neuroendocrine
      tumor is a rare cause of Sister Mary Joseph's nodule. 

PMID- 25584167
TI  - Learning style preferences of preclinical medical students in oman.
AB  - OBJECTIVE: Our study sought to assess the learning preferences of students
      studying in the preclinical years of the medical degree program at Oman Medical
      College, Sohar.  METHODS: In this descriptive, cross-sectional study, we
      administered a learning style questionnaire (VARK model) to 140 students to
      assess their preferred mode of learning, specifically the sensory modality by
      which they prefer to take in information.  RESULTS: Over one third (35%) of the
      respondents expressed their preference for a single mode of learning, either
      visual (8%), auditory (9%), read/write (9%), or kinesthetic (9%). The remaining
      students preferred learning using a combination of either two (14%), three (19%),
      or four (32%) sensory modalities.  CONCLUSION: The results of our study provide
      us with useful information to develop appropriate learning approaches to reach
      all types of learners at the college.

PMID- 25584168
TI  - Calcified kidney.

PMID- 25584169
TI  - Personalized management of IBD; is there any practical approach?

PMID- 25584170
TI  - Elemental diet and the nutritional treatment of Crohn's disease.

PMID- 25584173
TI  - Exploring the practical themes for medical education social accountability in
      Iran.
AB  - AIM: The purpose of this paper is to explore themes for enhancing socially
      accountability in medical education. BACKGROUND: Medical education in Iran
      experience new challenges due to the enormous influence of changes in technology,
      development of new methods of teaching and learning, student requirements,
      patient management, financial credit constraints, and social and economic
      developments. For responding to these, use of strategic thinking in order to make
      appropriate decisions is the only solution. Strategic plans need to formulate
      practical guides which can help accountable to people's reasonable expectations.
      PATIENTS AND METHODS: For this qualitative study, along with the 14(th)national
      conference on Medical Education in Iran, the opinions of experts were obtained
      during seven expert panels' group discussions, each lasting four hours and
      including 10 participants. Data were collected by audiotapes, which were then
      transcribed. Data analyzed using a thematic content analysis approach. Peer and
      member checking during analysis and data triangulation from other recent studies
      were used to increase the findings' trustworthiness. RESULTS: Among more than
      hundred meaning units groups identified the following eight main themes as
      affecting the social accountable medical education in Iran: organization of
      responsive education councils; development of community based courses;
      development in field training; organization of educational processes; homogeneity
      in educational rules and regulations; budget management, educational outcomes;
      educational programs in departments and groups. CONCLUSION: This study have found
      the main themes that might affecting social accountable medical education in
      Iran, where Iranian policymakers should consider those when plan to make changes
      in medical education and could potentially adopt the proven useful policies and
      strategies of other countries.

PMID- 25584172
TI  - Burden of gastrointestinal cancer in Asia; an overview.
AB  - The cancers in the digestive system including gastric cancer, colorectal cancer,
      liver cancer, esophageal cancer and pancreatic cancer are one of the most common
      cancers in Asia. The burden of GI cancer is increasing in Asia because of aging,
      growth of the population and the risk factors including smoking, obesity,
      changing lifestyle and high prevalence of H pylori, HBV and HCV. In most Asian
      countries, cancer control programs or early detection and treatment services are
      limited despite this increase. There are many people in the developing countries
      inside Asia who have no health insurance and many of them are too poor to go for
      screening tests, early detection or medical treatments. Therefore, it is
      important for the health organizations and governments in each country to
      recognize these groups and reduce the incidence and mortality of gastrointestinal
      cancers, using simple and economic screening test, vaccination and changing risk
      factors such as smoking, diet and lifestyle by education programs. 

PMID- 25584171
TI  - Introducing biomarker panel in esophageal, gastric, and colon cancers; a
      proteomic approach.
AB  - Cancer research is an attractive field in molecular biology and medicine. By
      applying large-scale tools such as advanced genomics and proteomics, cancer
      diagnosis and treatment have been improved greatly. Cancers of esophagus,
      gastric, and colon accounted for major health problem globally. Biomarker panel
      could bring out the accuracy for cancer evaluation tests as it can suggest a
      group of candidate molecules specified to particular malignancy in a way that
      distinguishing malignant tumors from benign, differentiating from other diseases,
      and identifying each stages with high specificity and sensitivity. In this
      review, a systematic search of unique protein markers reported by several
      proteomic literatures are classified in their specific cancer type group as novel
      panels for feasible accurate malignancy diagnosis and treatment. About thousands
      of introduced proteins were studied; however, a small number of them belonged to
      a specific kind of malignancy. In conclusion, despite the fact that combinatorial
      biomarkers appear to be hopeful, more evaluation of them is crucial to achieve
      the suitable biomarker panel for clinical application. This effort needs more
      investigations and researches for finding a specific and sensitive panel. 

PMID- 25584174
TI  - The importance of histologic parameters of lacteal involvement in cases of canine
      lymphoplasmacytic enteritis.
AB  - BACKGROUND: The most frequent form of inflammatory bowel disease (IBD) in dogs is
      represented histologically, by lymphoplasmacytic enteritis (LPE), a histological
      category, often associated with other morphologic alterations including
      lymphangiectasia (LE). However, literature data on this latter topic are quite
      scarce and have mostly been obtained in single reports or in small series. AIM:
      We evaluated some morphologic parameters of intestinal villi and lacteals in a
      large cohort of dogs, and correlated them with serum albumin and cholesterol
      values. PATIENTS AND METHODS: We investigated 136 dogs (94 with LPE, and 42 with
      gastrointestinal problems different from IBD) and analyzed their clinical,
      laboratory (albumin and cholesterol values), endoscopic, and histologic
      variables. RESULTS: The LPE group showed significantly impaired clinical,
      laboratory, endoscopic, and histologic variables compared to controls. Affected
      dogs showed significant correlations between canine inflammatory bowel disease
      activity index (CIBDAI) scores and endoscopic and histologic variables. Moreover,
      the grade of hematologic changes were strongly related to the intestinal
      histologic variables, in particular those concerning villous and lacteals
      morphology. CONCLUSION: Dogs with LPE had intestinal histologic abnormalities
      (height, width, height/width ratio, calculated for both villi and lacteals),
      whose degree correlated with the severity of hypoalbuminemia and
      hypocholesterolemia. Evaluation of endoscopic and histologic variables in
      association to the clinical findings may reveal useful insights for the
      pathogenesis of LPE and, hopefully, might lead to more targeted therapeutic
      approaches.

PMID- 25584175
TI  - Evaluation of cholestasis in Iranian infants less than three months of age.
AB  - AIM: The aim of this study is to find-out the possible etiologies in Iranian
      infants less than three months in Shiraz, South of Iran. BACKGROUND: Cholestatic
      jaundice most probably occurs due to a pathological condition and the most
      frequent causes in early infancy are neonatal hepatitis and biliary atresia.
      Early diagnosis and treatment of infantile cholestasis can improve prognosis of
      liver diseases by prevention of the complications of these disorders. PATIENTS
      AND METHODS: In this retrospective study, 122 infants under 3 months of age with
      cholestasis were studied in Nemazee Hospital (affiliated to Shiraz University of
      Medical Sciences) during the years 2001-2011. Demographic data, duration of
      jaundice, liver biopsy and the causes of cholestasis were recorded. RESULTS:
      There were 76 males (62.3%) and 46 females (37.7%) with a mean age of 54.4 +/-
      23.7 days. The most common clinical finding was jaundice that was seen in all
      patients (100%).The onset of jaundice was the first day to the fifty two days of
      age, with an average age of 15.6 +/- 16.1 days. Other findings included
      hepatomegaly in 92 patients (76.4%), clay-color stool in 54 (44.3%), and
      splenomegaly in 29 patients (23.8%). In this study, the most common causes of
      cholestasis were biliary atresia (30=24.6%), idiopathic neonatal hepatitis (30=
      24.6%) and bile ducts paucity (16=10.3). CONCLUSION: The results of this study
      showed that biliary atresia and neonatal hepatitis are the most common causes of
      infantile cholestasis in this area. It is recommended that biliary atresia should
      be discriminated from other forms of neonatal cholestasis.

PMID- 25584176
TI  - Effect of vitamin D3 supplementation on TNF-alpha serum level and disease
      activity index in Iranian IBD patients.
AB  - AIM: The aim of the study was to assess the effectiveness of vitamin D3 [1,
      25(OH)2D3] treatment in IBD with regard to tumor necrosis factor-alpha (TNF
      alpha) serum level and clinical disease activity index (CDAI). BACKGROUND:
      Vitamin D has immune-regulatory functions in experimental inflammatory bowel
      disease (IBD) and vitamin D deficiency is common in IBD patients. PATIENTS AND
      METHODS: This was a randomized clinical trial on 108 IBD patients with serum 25
      OHD levels less than 30ng/ml, which divided into vitamin D and control groups.
      Vitamin D group received 50000 IU vitamin D3 for 12 weeks. Before and after the
      study, TNF-alpha and 25-OHD serum levels were measured by ELISA method. Data were
      analyzed using paired t-test, chi-square test and Spearman correlation
      coefficient. P-values less than 0.05 were considered statistically significant.
      RESULTS: Before the intervention no significant difference was found between
      baseline characteristics and TNF-alpha serum level of two groups. After
      intervention TNF-alpha serum level reduced but this reduction was not
      statistically significant (p= 0.07, 95% CI: -0.45 to 8.14). The mean serum 25-OHD
      level of vitamin D increased from 15.54 to 67.89, which was statistically
      significant (p= 0.00, 95% CI: -61.40 to -43.30). TNF-alpha level was also
      associated significantly with CDAI before (Spearman's rho: 0.3, p<0.0001) and
      after (Spearman's rho: 0.27, P=0.01) intervention. CONCLUSION: Oral
      supplementation vitamin D3 significantly increased serum vitamin D levels and
      insignificantly reduced serum TNF-alpha level. More studies with larger samples
      would be beneficial to assess vitamin D3 supplementation efficient effect in IBD.

PMID- 25584178
TI  - Post gastroenteritis gluten intolerance.

PMID- 25584177
TI  - Synbiotic containing Bacillus coagulans and fructo-oligosaccharides for
      functional abdominal pain in children.
AB  - AIM: We evaluated the effectiveness of a synbiotic in the treatment of childhood
      functional abdominal pain (FAP). BACKGROUND: Probiotics are effective in the
      treatment of functional gastrointestinal disorders in adult patients, but there
      is lack of information in children. PATIENTS AND METHODS: Children with FAP,
      based on the Rome III criteria (n = 115, aged 6-18 years), were randomized to
      receive either synbiotic (Bacillus coagulans, Unique IS-2, 150 million spore plus
      FOS, 100 mg) twice daily or placebo for four weeks. Treatment response was
      defined as >= 2-point reduction in the 6-point self-rated pain scale or "no
      pain". Physician-rated global severity and improvement were also evaluated.
      Patients were followed for a total of 12 weeks. RESULTS: Eighty-eight patients
      completed the trial (45 with synbiotic). Response rate was higher with synbiotic
      than placebo after medication (60% vs. 39.5%, P = 0.044), but was not different
      between the two groups at week 12 (64.4% vs. 53.4%, P = 0.204). Difference
      between the two groups regarding the physician-rated global severity over the
      study period was not statistically significant (z = -1.87, P = 0.062). There was
      no significant difference between the two groups in physician-rated global
      improvement (week 4, P = 0.437; week 12, P = 0.111). Receiving synbiotic (OR
      2.608, 95% CI: 1.01-6.68) and baseline pain score (OR 2.21, 95% CI: 1.19-4.10)
      were predictors of treatment response after medication. CONCLUSION: The synbiotic
      containing Bacillus coagulans and FOS seems to be effective in the treatment of
      childhood FAP. Further trials are recommended in this regard.

PMID- 25584179
TI  - Elemental diets role in treatment of high ileostomy output and other
      gastrointestinal disorders.
AB  - Elemental diet (ED) has been used widely in the treatment of gastrointestinal
      disorders, especially with the management of Crohn's disease. This modality of
      diets provides all essential nutrients, and contains protein in the form of free
      amino acids that are theoretically easily absorbed. High output ileostomies are a
      rare but important complications of stoma formation following bowel surgery.
      Treatments could be challenging and include anti-diarrhoeals, octreotide and
      proton pump inhibitors. There is very little research regarding the use of
      elemental diets in the treatment of patients with post-operative high ileostomy
      outputs. Adequate management of high output ileostomies might prevent significant
      morbidity. In this case report, we describe a patient who underwent a subtotal
      colectomy for ulcerative colitis complicated by refractory high ileostomy output
      despite maximal standard medical therapy for years. The ileostomy output was
      dramatically reduced following the introduction of an elemental diet. This case
      suggests a possible role for the introduction of an elemental diet in the
      management of high output ileostomies. Besides presenting this case with high
      output ileostomy, we reviewed the role of ED in other gastrointestinal disorders.

PMID- 25584181
TI  - Recent advances in pancreatic disease.

PMID- 25584180
TI  - An unusual cause of abdominal pain.

PMID- 25584182
TI  - Radiosynthesis and in vivo evaluation of a novel sigma1 selective PET ligand.
AB  - The sigma1 receptor is an important target for CNS disorders. We previously
      identified a sigma1 ligand TZ3108 having highly potent (Ki-sigma1 = 0.48 nM) and
      selective affinity for sigma1 versus sigma2 receptors. TZ3108 was 18F-labeled
      with F-18 for in vivo evaluation. Biodistribution and blocking studies of
      [18F]TZ3108 in male Sprague-Dawley rats demonstrated high brain uptake, which was
      sigma1-specific with no in vivo defluorination. MicroPET studies in cynomolgus
      macaques showed high brain penetration of [18F]TZ3108; the regional brain
      distribution was consistent with that of the sigma1 receptor. Pseudo-equilibrium
      in the brain was reached ~ 45 min post-injection. Metabolite analysis of
      [18F]TZ3108 in NHP blood and rodent blood and brain revealed that ~ 70% parent
      remained in the plasma of NHPs 60 min post-injection and the major
      radiometabolite did not cross the blood-brain barrier in rats. In summary, the
      potent, selective and metabolically stable sigma1 specific radioligand
      [18F]TZ3108 represents a potentially useful PET radioligand for quantifying the
      sigma1 receptor in the brain.

PMID- 25584183
TI  - TypOn: the microbial typing ontology.
AB  - ABSTRACT: Bacterial identification and characterization at subspecies level is
      commonly known as Microbial Typing. Currently, these methodologies are
      fundamental tools in Clinical Microbiology and bacterial population genetics
      studies to track outbreaks and to study the dissemination and evolution of
      virulence or pathogenicity factors and antimicrobial resistance. Due to advances
      in DNA sequencing technology, these methods have evolved to become focused on
      sequence-based methodologies. The need to have a common understanding of the
      concepts described and the ability to share results within the community at a
      global level are increasingly important requisites for the continued development
      of portable and accurate sequence-based typing methods, especially with the
      recent introduction of Next Generation Sequencing (NGS) technologies. In this
      paper, we present an ontology designed for the sequence-based microbial typing
      field, capable of describing any of the sequence-based typing methodologies
      currently in use and being developed, including novel NGS based methods. This is
      a fundamental step to accurately describe, analyze, curate, and manage
      information for microbial typing based on sequence based typing methods.

PMID- 25584184
TI  - AISO: Annotation of Image Segments with Ontologies.
AB  - BACKGROUND: Large quantities of digital images are now generated for biological
      collections, including those developed in projects premised on the high
      throughput screening of genome-phenome experiments. These images often carry
      annotations on taxonomy and observable features, such as anatomical structures
      and phenotype variations often recorded in response to the environmental factors
      under which the organisms were sampled. At present, most of these annotations are
      described in free text, may involve limited use of non-standard vocabularies, and
      rarely specify precise coordinates of features on the image plane such that a
      computer vision algorithm could identify, extract and annotate them. Therefore,
      researchers and curators need a tool that can identify and demarcate features in
      an image plane and allow their annotation with semantically contextual ontology
      terms. Such a tool would generate data useful for inter and intra-specific
      comparison and encourage the integration of curation standards. In the future,
      quality annotated image segments may provide training data sets for developing
      machine learning applications for automated image annotation. RESULTS: We
      developed a novel image segmentation and annotation software application,
      "Annotation of Image Segments with Ontologies" (AISO). The tool enables
      researchers and curators to delineate portions of an image into multiple
      highlighted segments and annotate them with an ontology-based controlled
      vocabulary. AISO is a freely available Java-based desktop application and runs on
      multiple platforms. It can be downloaded at
      http://www.plantontology.org/software/AISO. CONCLUSIONS: AISO enables curators
      and researchers to annotate digital images with ontology terms in a manner which
      ensures the future computational value of the annotated images. We foresee uses
      for such data-encoded image annotations in biological data mining, machine
      learning, predictive annotation, semantic inference, and comparative analyses.

PMID- 25584186
TI  - The impact of preventive health behaviour and social factors on visits to the
      doctor.
AB  - BACKGROUND: The aim of this study is to examine the joint impact of preventive
      health behavior (PHB) and social and demographic factors on the utilization of
      primary and secondary medical care under a universal health care system, as
      measured by visits to the doctor, who were categorized as either a General
      Practitioner (GP) or Specialist Doctor (SD). METHODS: An ordered probit model was
      utilized to analyze data obtained from the 2009 Israeli National Health Survey.
      The problem of endogeneity between PHB factors and visits to GP was approached
      using the two-stage residuals inclusion and instrumental variables method.
      RESULTS: We found a positive effect of PHB on visits to the doctor while the
      addition of the PHB factors to the independent variables resulted in important
      changes in explaining visits to GP (in values of the estimates, in their sign,
      and in their statistical significance), and only in slight changes for visits to
      SD. A 1% increase in PHB factors results in increasing the probability to visit
      General Practitioner in the last year in 0.6%. The following variables were
      identified as significant in explaining frequency of visits to the doctor: PHB,
      socio-economic status (pro-poor for visits to GP, pro-rich for visits to SD),
      location (for visits to SD), gender, age (age 60 or greater being a negative
      factor for visits to GP and a positive factor for visits to SD), chronic
      diseases, and marital status (being married was a negative factor for visits to
      GP and a positive factor for visits to SD). CONCLUSIONS: There is a need for
      allowing for endogeneity in examining the impact of PHB, social and demographic
      factors on visits to GP in a population under universal health insurance. For
      disadvantaged populations with low SES and those living in peripheral districts,
      the value of IndPrev is lower than for populations with high SES and living in
      the center of the country. Examining the impact of these factors, significant
      differences in the importance and sometimes even in the sign of their influence
      on visits to different categories of doctors - GP and SD, are found.

PMID- 25584187
TI  - Examining professional boundaries between nurses and physicians in neonatal
      intensive care units.
AB  - BACKGROUND: Medical and technological developments, financial constraints and a
      shortage of physicians have made it necessary to re-examine professional
      boundaries between physicians and nurses. Israel's manpower shortage in Neonatal
      Intensive Care Units (NICUs) has changed the responsibility and authority of
      nurses. However, these changes have not evolved into a uniform policy defining
      the division of responsibility between physicians and nurses. This study was
      designed to examine the work processes and actual division of labor between NICU
      physicians and nurses; the attitude of physicians and nurses to greater
      empowerment of the nursing role; and to suggest a model to regulate work
      processes and develop the role of neonatal nurse specialists in NICUs. METHODS:
      Open interviews with NICU physician-directors and head nurses and a cross
      sectional survey of some 50% of the physicians and nurses at 22 hospital NICUs (N
      = 430). RESULTS: Main problems of NICUs: physician shortage, deficient
      infrastructures, fragmented work processes. Nurses do not perform many practices
      allowed to them due to the need for organizational approval and their own
      unawareness. Conversely, they sometimes conduct procedures and make decisions
      outside of their authority. Most physicians agree that nurse graduates of Post
      Basic Education training (PBE) should be authorized to independently perform such
      activities as resuscitation and medication balancing while reserving invasive
      procedures for physicians. It is widely agreed that broadening the authority of
      nurses would improve the quality of NICU care even though it would increase the
      nursing workload. CONCLUSIONS: The study provides important input into decisions
      about authorizing nurses over complete practice areas rather than isolated
      activities; the need to remove institutional restrictions on tasks currently
      permitted to nurses; introducing teamwork from within the NICUs, and expanding
      nursing decision-making. The study reveals that there is a basis on which to to
      build the role of the neonatal nurse,since most NICU nurses have the suitable
      academic and clinical training.

PMID- 25584188
TI  - The contribution of comprehensive geriatric assessment to primary care
      physicians.
AB  - BACKGROUND: To provide quality care to the growing number of older patients,
      primary care physicians (PCPs) will require support from geriatric specialists.
      Multidisciplinary comprehensive geriatric assessment (CGA) has been found to
      improve outcomes in older people. This study explored the contribution of CGA to
      the management of older patients by their PCPs; PCP attitudes to CGA; and PCP
      satisfaction with CGA. METHODS: Two hundred PCPs in an Israeli Preferred Provider
      Organization were interviewed as part of an evaluative study of the contribution
      of a national outpatient CGA program to older patients, their families and
      physicians. RESULTS: The main reasons for referral to CGA were cognitive
      impairment and rapid functional decline. Three domains described the contribution
      of CGA to PCPs: medical treatment, support in counseling patients, and treatment
      of cognitive impairment. About 69% of PCPs definitely agreed that CGA more fully
      addressed the physical, mental and social needs of patients than other
      consultative clinics. About half were very satisfied with the CGA staff's
      attitudes to patients, their families and to the PCP. CONCLUSIONS: CGA
      contributed significantly to the care provided to older patients by PCPs. The
      expansion of CGA services deserves consideration.

PMID- 25584185
TI  - What determines a leaf's shape?
AB  - The independent origin and evolution of leaves as small, simple microphylls or
      larger, more complex megaphylls in plants has shaped and influenced the natural
      composition of the environment. Significant contributions have come from
      megaphyllous leaves, characterized usually as flat, thin lamina entrenched with
      photosynthetic organelles and stomata, which serve as the basis of primary
      productivity. During the course of evolution, the megaphylls have attained
      complexity not only in size or venation patterns but also in shape. This has
      fascinated scientists worldwide, and research has progressed tremendously in
      understanding the concept of leaf shape determination. Here, we review these
      studies and discuss the various factors that contributed towards shaping the
      leaf; initiated as a small bulge on the periphery of the shoot apical meristem
      (SAM) followed by asymmetric outgrowth, expansion and maturation until final
      shape is achieved. We found that the underlying factors governing these processes
      are inherently genetic: PIN1 and KNOX1 are indicators of leaf initiation, HD
      ZIPIII, KANADI, and YABBY specify leaf outgrowth while ANGUSTIFOLIA3 and GROWTH
      REGULATING FACTOR5 control leaf expansion and maturation; besides, recent
      research has identified new players such as APUM23, known to specify leaf
      polarity. In addition to genetic control, environmental factors also play an
      important role during the final adjustment of leaf shape. This immense amount of
      information available will serve as the basis for studying and understanding
      innovative leaf morphologies viz. the pitchers of the carnivorous plant Nepenthes
      which have evolved to provide additional support to the plant survival in its
      nutrient-deficient habitat. In hindsight, formation of the pitcher tube in
      Nepenthes might involve the recruitment of similar genetic mechanisms that occur
      during sympetaly in Petunia. 

PMID- 25584189
TI  - IJHPR comes of age.
AB  - The Israel Journal of Health Policy Research (IJHPR) is about to complete its
      third year of publication. Over the past year, the journal received its first
      impact factor, three of its articles crossed the 10,000 accesses threshold,
      submissions increased by 50%, and the journal published its fifth article
      collection. These accomplishments are due to the combined efforts of the National
      Institute of Health Policy and its leadership team, IJHPR's editorial board, our
      publisher BioMed Central, and the journal's authors, commentators and reviewers
      from Israel and around the world. In Jewish tradition, the transition from a new
      endeavor's third year to its fourth year is full of significance, reflecting a
      phase transition in terms of maturity and stability. After 3 years of
      publication, IJHPR is also in the process of moving into a new phase; a more
      mature phase, with greater stability and a firmer place in the professional
      literature. We hope that this stability can be used as a springboard for further
      innovation, experimentation and growth. 

PMID- 25584190
TI  - Altered dietary methionine differentially impacts glutathione and methionine
      metabolism in long-living growth hormone-deficient Ames dwarf and wild-type mice.
AB  - BACKGROUND: Extending mammalian health span and life span has been achieved under
      a variety of dietary restriction protocols. Reducing the intake of a specific
      amino acid has also been shown to extend health and longevity. We recently
      reported that methionine (MET) restriction is not effective in life span
      extension in growth hormone (GH) signaling mutants. To better understand the
      apparent necessity of GH in the 'sensing' of altered dietary MET, the current
      study was designed to evaluate MET and glutathione (GSH) metabolism (as well as
      other pathways) in long-living GH-deficient Ames dwarf and wild-type mice
      following 8 weeks of restricted (0.16%), low (0.43%), or enriched (1.3%) dietary
      MET consumption. Metabolite expression was examined in liver tissue, while gene
      and protein expression were evaluated in liver, kidney, and muscle tissues.
      RESULTS: Body weight was maintained in dwarf mice on the MET diets, while wild
      type mice on higher levels of MET gained weight. Liver MET levels were similar in
      Ames mice, while several MET pathway enzymes were elevated regardless of dietary
      MET intake. Transsulfuration enzymes were also elevated in Ames mice but
      differences in cysteine levels were not different between genotypes. Dwarf mice
      maintained higher levels of GSH on MET restriction compared to wild-type mice,
      while genotype and diet effects were also detected in thioredoxin and
      glutaredoxin. MET restriction increased transmethylation in both genotypes as
      indicated by increased S-adenosylmethionine (SAM), betaine, and dimethylglycine.
      Diet did not impact levels of glycolytic components, but dwarf mice exhibited
      higher levels of key members of this pathway. Coenzyme A and measures of fatty
      acid oxidation were elevated in dwarf mice and unaffected by diet. CONCLUSIONS:
      This component analysis between Ames and wild-type mice suggests that the life
      span differences observed may result from the atypical MET metabolism and
      downstream effects on multiple systems. The overall lack of responsiveness to the
      different diets is well reflected across many metabolic pathways in dwarf mice
      indicating the importance of GH signaling in the ability to discriminate dietary
      amino acid levels.

PMID- 25584191
TI  - Standards of suitability for the management of chronic obstructive respiratory
      diseases.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) ranks third as cause of
      mortality and disability-adjusted life years (DALY) worldwide and also in Italy
      it imposes a huge health, social and economic load. Early symptoms of COPD are
      often disregarded by patients and physicians, spirometry is underutilized, and
      the diagnosis is delayed till the disease has reached a distinct severity level.
      Despite the availability of various guidelines, the behavior of health workers
      involved in the management of COPD is still rather unlike. These considerations
      are the reason why in October 2013 AIMAR (Interdisciplinary Scientific
      Association for Research in Lung Disease) devised and organized a "Third
      Consensus Conference", aimed at pointing out the standards of suitability for
      COPD management. In this context three important topics of discussion were
      identified: early and more widespread diagnosis, management of acute and subacute
      phases, long-term assistance to chronic patients. METHODS: The procedure
      recommended by the Italian Health Superior Institute (ISS) for Consensus
      Conferences organization was applied. The Conference was structured in three
      sessions, each dealing with one of the above mentioned topics and including a
      short update of the subject-matter and presentation, discussion and voting of
      some statements with a choice ranging from total agreement to total disagreement
      or no knowledge. The results of voting were eventually recorded in the document,
      reviewed by an independent jury, that forms the substance of this paper. RESULTS:
      The essential role of spirometry, the need for distinguish between different COPD
      phenotypes, and the obligatoriness to base on the blood gas analysis findings the
      long-term oxygen therapy, were largely agreed, as well as the need for
      interventions aimed at decreasing the rate of acute exacerbations. More specific
      topics like the use of noninvasive ventilation, recognizing the factors affecting
      outcome and mortality, the choice of pharmacological and non pharmacological
      treatments in COPD patients led to lively discussing, but they did not always
      reach the total agreement, probably because of insufficient familiarity with
      these problems and of diversities in organization and instruments availability.
      The chronic respiratory assistance was treated with particular regard to smoking
      cessation, whose implementation is still insufficient. Many doubts rose due to
      uncertainty, lack of ability and standardization of procedures, insufficient
      institutional support, and difficulties to realize a network for assistance to
      chronic patients. CONCLUSIONS: The results of this Third Consensus Conference
      revealed some certainties and many doubts and diversities of view also on topics
      whose importance is well demonstrated in scientific literature. Thus, there is
      still a long distance to cover before reaching a suitable standardization of COPD
      management and such situation urges the need for improving not only the health
      professional's operativeness but also the organizational support by competent
      institutions. In this context some initiatives organized by AIMAR in cooperation
      with other respiratory scientific societies and patients' associations are going
      on.

PMID- 25584193
TI  - Effects of core strength training using stable versus unstable surfaces on
      physical fitness in adolescents: a randomized controlled trial.
AB  - BACKGROUND: It has been demonstrated that core strength training is an effective
      means to enhance trunk muscle strength (TMS) and proxies of physical fitness in
      youth. Of note, cross-sectional studies revealed that the inclusion of unstable
      elements in core strengthening exercises produced increases in trunk muscle
      activity and thus provide potential extra training stimuli for performance
      enhancement. Thus, utilizing unstable surfaces during core strength training may
      even produce larger performance gains. However, the effects of core strength
      training using unstable surfaces are unresolved in youth. This randomized
      controlled study specifically investigated the effects of core strength training
      performed on stable surfaces (CSTS) compared to unstable surfaces (CSTU) on
      physical fitness in school-aged children. METHODS: Twenty-seven (14 girls, 13
      boys) healthy subjects (mean age: 14 +/- 1 years, age range: 13-15 years) were
      randomly assigned to a CSTS (n = 13) or a CSTU (n = 14) group. Both training
      programs lasted 6 weeks (2 sessions/week) and included frontal, dorsal, and
      lateral core exercises. During CSTU, these exercises were conducted on unstable
      surfaces (e.g., TOGU(c) DYNAIR CUSSIONS, THERA-BAND(c) STABILITY TRAINER).
      RESULTS: Significant main effects of Time (pre vs. post) were observed for the
      TMS tests (8-22%, f = 0.47-0.76), the jumping sideways test (4-5%, f = 1.07), and
      the Y balance test (2-3%, f = 0.46-0.49). Trends towards significance were found
      for the standing long jump test (1-3%, f = 0.39) and the stand-and-reach test (0
      2%, f = 0.39). We could not detect any significant main effects of Group.
      Significant Time x Group interactions were detected for the stand-and-reach test
      in favour of the CSTU group (2%, f = 0.54). CONCLUSIONS: Core strength training
      resulted in significant increases in proxies of physical fitness in adolescents.
      However, CSTU as compared to CSTS had only limited additional effects (i.e.,
      stand-and-reach test). Consequently, if the goal of training is to enhance
      physical fitness, then CSTU has limited advantages over CSTS. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02290457 Registered 13 November 2014.

PMID- 25584192
TI  - Bimodal Imaging Using Neodymium Doped Gadolinium Fluoride Nanocrystals with Near
      Infrared to Near-Infrared Downconversion Luminescence and Magnetic Resonance
      Properties.
AB  - Here we report the synthesis, characterization and application of a
      multifunctional surface functionalized GdF3:Nd3+ nanophosphor that exhibits
      efficient near infrared (NIR) fluorescence as well as magnetic properties, which
      can be utilized for bimodal imaging in medical applications. The nanoparticles
      are small with an average size of 5 nm and form stable colloids that last for
      several weeks without settling, enabling the use for several biomedical and
      photonic applications. Their excellent NIR properties, such as nearly 11 %
      quantum yield of the 1064 nm emission, make them ideal contrast agents and
      biomarkers for in vitro and in vivo NIR optical bioimaging. The nanophosphors
      which were coated with poly(maleic anhydride- alt-1-octadicene) (PMAO) were
      implemented in cellular imaging and show no significant cellular toxicity for
      concentrations up to 200 MUg ml-1. Furthermore, the incorporation of Gd into the
      nanocrystalline structure supplies exceptional magnetic properties, making them
      ideal for use as magnetic resonance imaging (MRI) contrast agents. The utility of
      these NIR emitting nanoparticles in infrared bioimaging and as contrast agent in
      magnetic resonance imaging was demonstrated by confocal imaging, magnetic
      resonance and tissue experiments.

PMID- 25584195
TI  - Effect of Amphotericin B Nanodisks on Leishmania major Infected Mice.
AB  - OBJECTIVE: To assess the efficacy of a novel formulation of the polyene
      antibiotic, amphotericin B (AMB), as therapy for cutaneous leishmaniasis in
      different mouse strains. METHODS: (AMB), was formulated into water-soluble
      transport particles, termed nanodisks (ND). Balb/c and CH3 mice infected with
      Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on
      Day 1 and day 7, via the tail vein. Mice were sacrificed 25 or 50 days post
      inoculation and tissue histology evaluated. Balb/c mice treated with vehicle or
      empty ND showed signs of severe infection while CH3 mice had less inflammation
      and fewer parasites. AMB-ND treatment (2 mg/kg) had a marked therapeutic effect
      on L. major infected Balb/c mice and a discernable therapeutic benefit on CH3
      mice. CONCLUSIONS: AMB-ND is efficacious in the treatment of cutaneous
      leishmaniasis in both susceptible and resistant mouse strains. It may be inferred
      that AMB-ND may be useful for prophylactic and/or treatment of early stage
      Leishmania spp. infection.

PMID- 25584196
TI  - Monitoring and reporting hospital-acquired conditions: a federalist approach.
AB  - BACKGROUND: Serious adverse events that occur in hospitals rank as a leading
      cause of preventable death in the United States. Many states operate reporting
      systems to monitor and publicly report serious adverse events, a subset that
      falls under Medicare's Hospital-Acquired Conditions (HACs). PURPOSES: Identify
      and describe state efforts, and the supporting role of federal initiatives, to
      track and report HACs and other serious adverse events. DATA SOURCES: Document
      review of state and federal reports, databases, and policies for HACs and other
      serious adverse events; conduct semi-structured telephone interviews with state
      health department officials and directors of patient safety organizations.
      RESULTS: Thirty-two states and the District of Columbia (D.C.) track at least one
      Medicare HAC. Five states collect nearly all ten Medicare HACs (9-10). Eighteen
      states and D.C. track events through both a state-based reporting system and the
      Centers for Disease Control National Healthcare Safety Network (NHSN) for health
      care associated infections (HAI). For serious adverse events, most states either
      partially or fully adopted the National Quality Forum's Serious Reportable
      Events. For HAIs, thirty states and D.C. mandate reporting through NHSN. States
      interviewed reported that Medicare's choice of HACs for nonpayment had at least a
      partial influence on which serious adverse events required reporting.
      CONCLUSIONS: Many states use the collected data on HACs and other events for
      quality improvement initiatives and to provide greater transparency through
      public reporting. More work and research is needed to develop a national
      reporting system template that has standard definitions, methodology, and
      reporting.

PMID- 25584194
TI  - Respiratory Viral Infections and Subversion of Cellular Antioxidant Defenses.
AB  - Reactive oxygen species (ROS) formation is part of normal cellular aerobic
      metabolism, due to respiration and oxidation of nutrients in order to generate
      energy. Low levels of ROS are involved in cellular signaling and are well
      controlled by the cellular antioxidant defense system. Elevated levels of ROS
      generation due to pollutants, toxins and radiation exposure, as well as
      infections, are associated with oxidative stress causing cellular damage. Several
      respiratory viruses, including respiratory syncytial virus (RSV), human
      metapneumovirus (hMPV) and influenza, induce increased ROS formation, both
      intracellularly and as a result of increased inflammatory cell recruitment at the
      site of infection. They also reduce antioxidant enzyme (AOE) levels and/or
      activity, leading to unbalanced oxidative-antioxidant status and subsequent
      oxidative cell damage. Expression of several AOE is controlled by the activation
      of the nuclear transcription factor NF-E2-related factor 2 (Nrf2), through
      binding to the antioxidant responsive element (ARE) present in the AOE gene
      promoters. While exposure to several pro-oxidant stimuli usually leads to Nrf2
      activation and upregulation of AOE expression, respiratory viral infections are
      associated with inhibition of AOE expression/activity, which in the case of RSV
      and hMPV is associated with reduced Nrf2 nuclear localization, decreased cellular
      levels and reduced ARE-dependent gene transcription. Therefore, administration of
      antioxidant mimetics or Nrf2 inducers represents potential viable therapeutic
      approaches to viral-induced diseases, such as respiratory infections and other
      infections associated with decreased cellular antioxidant capacity.

PMID- 25584198
TI  - The Sculpting of the Mycobacterium tuberculosis Genome by Host Cell-Derived
      Pressures.
AB  - Mycobacterium tuberculosis is an incredibly successful pathogen with an
      extraordinary penetrance of its target host population. The ability to infect
      many yet cause disease in few is undoubtedly central to this success. This
      ability relies on sensing and responding to the changing environments encountered
      during the course of disease in the human host. This chapter discusses these
      environmental cues and stresses, and explores how the genome of Mtb has evolved
      under the purifying selections that they exert. In analyzing the response of Mtb
      to a broad range of intracellular pressures it is clear that, despite genome down
      sizing, Mtb has retained an extraordinary flexibility in central carbon
      metabolism. We believe that it is this metabolic plasticity, more than any of the
      virulence factors, that is the foundation for Mtb's qualities of endurance. 

PMID- 25584201
TI  - Comparison of the volar and medial approach in peripheral block of ulnar nerve at
      the wrist - a cadaveric study.
AB  - CONTEXT: Two standard approaches are described to block the ulnar nerve at wrist.
      These include a) the traditional Volar approach where the needle is inserted
      lateral to tendon of flexor carpi ulnaris (FCU) b) Medial approach where the
      needle is inserted posterior to the tendon of FCU. Caution must be exercised to
      avoid puncture of the ulnar artery and/or intraneural injection of the ulnar
      nerve in both the approaches. AIM: This study compares the volar and medial
      approach to the peripheral block of ulnar nerve at the wrist. The objective was
      two fold: a) to analyze the position of the ulnar nerve and the ulnar artery in
      relation to the Flexor Carpi Ulnaris tendon b) to assess the risk of injury to
      ulnar artery in both the volar and medial approach. SETTINGS AND DESIGNS: Twelve
      cadaveric upper limbs were used and both approaches compared by an observational
      study. MATERIALS AND METHODS: Two 18 G needles were inserted up to a depth of 7
      mm using the standard volar and medial approach. The pattern of arrangement and
      positions of the ulnar artery and nerve in relation to FCU tendon were observed.
      The distance between the tip of needle and its proximity to the ulnar artery, and
      risk of injury were determined. Statistical analysis was done using SPSS for
      Windows, Version 16.0. Chicago, SPSS Inc. RESULTS: Three patterns of arrangement
      and position of the ulnar nerve and artery were observed. Puncture of ulnar
      artery was seen in 50% of cases in the volar approach as compared to no injury at
      all in the medial approach. The ulnar artery is highly liable to injury during
      the volar approach in type I and II and safe only in type III arrangement of
      ulnar artery. The medial approach showed no injury to the ulnar artery or nerve
      at a penetration depth of 7mm. CONCLUSION: The medial approach is safer compared
      to volar approach for peripheral block of ulnar nerve at wrist.

PMID- 25584199
TI  - The mosquito microbiota influences vector competence for human pathogens.
AB  - The midgut of insect vectors of human disease contains not only pathogens harmful
      to human health, but also a diverse microbiota. This microbiota can influence
      insects' susceptibility to human pathogens, and the capacity to transmit them,
      through different mechanisms. Understanding the interaction between the vector,
      its microbiota and transmitted pathogens will provide novel opportunities to
      limit disease transmission.

PMID- 25584200
TI  - Peripheral olfactory signaling in insects.
AB  - Olfactory signaling is a crucial component in the life history of insects. The
      development of precise and parallel mechanisms to analyze the tremendous amount
      of chemical information from the environment and other sources has been essential
      to their evolutionary success. Considerable progress has been made in the study
      of insect olfaction fueled by bioinformatics- based utilization of genomics along
      with rapid advances in functional analyses. Here we review recent progress in our
      rapidly emerging understanding of insect peripheral sensory reception and signal
      transduction. These studies reveal that the nearly unlimited chemical space
      insects encounter is covered by distinct chemosensory receptor repertoires that
      are generally derived by species-specific, rapid gene gain and loss, reflecting
      the evolutionary consequences of adaptation to meet their specific biological
      needs. While diverse molecular mechanisms have been put forth, often in the
      context of controversial models, the characterization of the ubiquitous, highly
      conserved and insect-specific Orco odorant receptor co-receptor has opened the
      door to the design and development of novel insect control methods to target
      agricultural pests, disease vectors and even nuisance insects.

PMID- 25584202
TI  - Study of variations in the branching pattern of lower subscapular nerve.
AB  - BACKGROUND: Variations in the origin of lower subscapular nerve of the posterior
      cord of brachial plexus are important during surgical approaches to the axilla
      and upper arm, administration of anesthetic blocks, interpreting effects of
      nervous compressions and in repair of plexus injuries. The patterns of origin
      show population differences. Data from the South Indian population is scarce.
      OBJECTIVE: To describe the variations in the origin of the lower subscapular
      nerve of the posterior cord of brachial plexus in the South Indian population.
      MATERIALS AND METHODS: Forty brachial plexuses from 20 formalin fixed cadavers
      were explored by gross dissection. Origin and order of branching of lower
      subscapular nerve was recorded. Representative photographs were then taken using
      a digital camera (Sony Cyber shot R, W200, 7.2 Megapixels). RESULTS: Lower
      subscapular nerves had origin from axillary nerve in 57.5% of specimens, in 37.5%
      specimens, it was originating from the posterior cord and in 5% of specimens it
      arose from common trunk. CONCLUSION: Lower subscapular nerves in studied
      population display a wide range of variations. Anesthesiologists administering
      local anesthetic blocks, clinicians interpreting effects of nerve injuries of the
      upper limb and surgeons operating in the axilla should be aware of these patterns
      to avoid in advertent injury.

PMID- 25584203
TI  - Prevalence and Mophometry of Os Peroneum amongst Central Indians.
AB  - INTRODUCTION: Os Peroneum is round or oval shaped sesamoid within the substance
      of the Peroneus longus tendon as it plays on the Cuboid bone. MATERIALS AND
      METHODS: Thirty six embalmed cadavers were dissected bilaterally. Lateral part of
      foot and sole was dissected to expose Peroneus longus tendon and Os Peroneum.
      Measurements of Os Peroneum and articular surfaces of cuboid (calcaneum) were
      taken by the Digital Vernier Caliper. Histological and Radiological Examinations
      of Os Peroneum were also done. OBSERVATION: A flattened oval enlargement i.e. Os
      Peroneum was found in all the tendons examined. The deep surface of Os Peroneum
      (i.e. articular surface) was concave, smooth and shiny; sometimes divided into
      two parts. There was a well defined convex articular facet on the Cuboid at the
      proximal end of the peroneal sulcus, which sometimes extended proximally on to
      the Calcaneum forming a synovial joint. RESULTS: Average length of Os Peroneum
      was found to be 13.35 mm (Right - 13.35 mm, Left - 13.35 mm). Average breadth of
      Os Peroneum was 8.96 mm (Right - 8.87 mm, Left - 9.05 mm). Average thickness of
      Os Peroneum was 4.11 mm (Right - 4.13 mm, Left - 4.10 mm). Incidence of double
      articular facets on cuboid and Calcaneum was more on the right side (25.80%) than
      the left (16.20%). CONCLUSION: Findings suggest that Os Peroneum is present at
      the site of angulations of Peroneus Longus tendon with attendant change in
      direction and the exposure to various stresses and strains leading to its
      thickening and formation of Os Peroneum.

PMID- 25584204
TI  - Morphometry, asymmetry and variations of the sylvian fissure and sulci bordering
      and within the pars triangularis and pars operculum: an autopsy study.
AB  - OBJECTIVE: Speech and Language, one of the most lateralized of all cerebral
      functions is located within the pars opercularis (PO) and pars triangularis (PT).
      There is also inter-hemispheric variability of the sulcal contours bordering
      these areas. The study was undertaken to note the morphometry, asymmetry and
      variations of the Sylvian fissure (SF), and the sulci bordering and within the PO
      and PT. MATERIALS AND METHODS: An adult autopsy cadaveric study was carried. The
      measurements made amongst others, included fronto-occipital cerebral length,
      cerebral width, Sylvian fissure length, and anterior Sylvian point (ASP) to
      inferior Rolandic point distance. The PT and PO were also studied. RESULTS: Sixty
      two adult cadaveric hemispheres were studied. The SF length on the right
      (mean=84.3mm, median=88mm) was significantly shorter than that on the left
      (mean=89.4mm, median=92.0mm) (p=0.037). The anterior ascending and anterior
      horizontal rami of the SF arose from the ASP and either divides at this point (43
      hemispheres, 69.4%) or have a common short stem before separating distally giving
      a Y-shape configuration. The triangularis sulcus was noted in 49 hemispheres
      (79%) while the diagonal sulcus was noted in 26 hemispheres (41.9%). CONCLUSION:
      The left SF was significantly longer than the right and both were positively
      correlated. The presence of the triangularis sulcus was not dependent on the side
      (p=0.348) or gender (0.622) unlike the diagonal sulcus was side dependent (p=
      0.000).

PMID- 25584205
TI  - Unusual infra-clavicular venous circle - a case report.
AB  - Currently, numerous invasive procedures are preferred in cephalic vein (CV) and
      axillary vein (AV) than other veins in the neck. Anatomical variations of these
      veins in the axilla and delto-pectoral region may result in failure and
      postoperative complications of the procedures. A thorough knowledge of possible
      variations of AV and CV may immensely contribute to the success of any such
      procedures where the veins are involved. We report the variations of the CV,
      tributaries of AV and median cubital vein. We observed a venous circle formed by
      the tributaries of AV in the infra-clavicular region, deep to the pectoral
      muscles. Cephalic vein joined proximal end of venous circle just before ending
      into AV. Further, duplication of the median cubital vein was observed. 

PMID- 25584206
TI  - Assessment of lung function by spirometry and diffusion study and effect of
      glycemic control on pulmonary function in type 2 diabetes mellitus patients of
      the eastern India.
AB  - INTRODUCTION: There are so many complications involving eyes, kidneys, lungs and
      nerves associated with diabetes. But, pulmonary complications are poorly
      characterized among eastern Indian diabetic populations. AIMS AND OBJECTIVES: To
      assess pulmonary function in patients with type 2 diabetes mellitus. To find out
      correlation of the pulmonary functions test variables with Glycemic control.
      MATERIALS AND METHODS: Total of 60 type 2 diabetes patient of age between 35-55 y
      and same number of age and sex matched apparently healthy control individual were
      included in the present study. All subjects were evaluated for PFT by flow
      sensitive spirometer (RMS HELIOS-401), the spirometric parameters were measured
      as a percentage of predicted and DLCO (by single breath technique). HBA1c of all
      cases were measured and they were grouped according to HBA1c level (Group-a =>7%,
      Group-b =6%-7%, Group-c =<6%). RESULTS: Significant differences in the
      spirometric parameters (FVC, FEV1/FVC) and diffusion capacity (DLCO% and DL/VA%)
      existed between cases and controls. There was a significant decrease in FVC, DLCO
      and DL/VA and significant increase in FEV1/FVC in that groups having HBA1c level
      >7% than the other groups. FEV1, FVC, DLCO, and DL/VA were negatively correlated
      with HbA1c where as FEV1/FVC has positive association with HbA1c. CONCLUSION:
      Significant deterioration of lung function and diffusing capacity was observed in
      type 2 diabetes patients with poor glycemic control.

PMID- 25584207
TI  - Study the effect of age and gender related differences on common paper and pencil
      neurocognitive tests in adolescents.
AB  - BACKGROUND: Neurocognitive tests are routinely used to assess cognitive domains
      in the adolescents for assessing cognitive deficits and for therapeutic
      interventions. Now they are being used to assess their mental abilities in
      athletics too. AIM: To study the effect of age and gender differences on
      routinely used common paper and pencil neuro-cognitive tests in adolescents and
      present the trends of normative data of Indian adolescent population. SETTINGS
      AND DESIGN: Present study was conducted as a joint collaboration between
      Department of Physiology and Jawahar Navodaya school, Puducherry, India.
      MATERIALS AND METHODS: Four hundred and thirty nine adolescents in the age group
      of 12 to 17 y (M = 250, F= 189) were selected in the present study after meeting
      the inclusion and exclusion criteria. Subjects were administered commonly used
      paper and pencil neuropsychological tests in the following order: Two Target
      Letter Cancellation test, Trail Making test A and B, Ruff Figural Fluency test
      (RFFT). STATISTICAL ANALYSIS: We divided the students based on their age into six
      groups - from age 12-17. Neurocognitive parameters were compared between these
      age groups using one-way-ANOVA with Bonferroni post-hoc test. Only the p-values
      for one, two and three year difference were considered. The same analysis was
      repeated for each gender separately. We compared males and females from the
      entire sample using unpaired t test. We then repeated the same test to compare
      males and females in each age group separately. Pearsons correlation was done to
      find correlation between the neurocognitive test parameters using the entire
      sample size. Then the correlation was done again after adjusting for age. All the
      statistical analysis was done using Statistical package for social sciences
      (SPSS) version 19. RESULTS: Year wise normative data has been presented for all
      the age groups from 12 y onwards to 17 y. The results showed a consistent
      improvement in performance on the tested neuro-psychological tests with
      increasing age in adolescents. Overall gender comparison showed significantly
      better RFFT performance in males than females, with a non-significant difference
      in other tested parameters. However, no such difference was observed when the
      comparison was made within each age group. CONCLUSION: Improvement in the tests
      as a function of age may represent ongoing neuro-maturational process. Overall
      gender comparison from 12 to 17 y demonstrates that males performed better on
      nonverbal fluency task and strategic analysis suggesting difference in cognitive
      growth patterns but changes are so slow and gradual that no significant
      difference was observed at each intra-age group gender comparison. Baseline
      testing should be at least repeated once in two years.

PMID- 25584208
TI  - Normal pregnancy- a state of insulin resistance.
AB  - BACKGROUND: Purpose of insulin resistance (IR) adapted by mother is to deliver
      enough quantity of nutrients to the growing fetus. Many maternal hormones and
      factors play role in causation of IR during pregnancy. AIM: The study aims at
      evaluating IR at different trimesters of pregnancy. MATERIALS AND METHODS:
      Pregnant women at 1(st), 2(nd) and 3(rd) trimester were grouped into groups I, II
      and III respectively (n=20 in each group). Healthy non-pregnant women were taken
      as controls (n=30). Fasting plasma glucose (FPG) and fasting serum insulin (FSI)
      were measured and IR indices such as fasting glucose to insulin ratio (FGIR),
      quantitative insulin sensitivity check index (QUICKI), log FSI and log HOMA1-IR
      were calculated. The student's t-test and one way Analysis of variance (ANOVA)
      were used for data analysis. RESULTS: The mean FSI, log FSI and log HOMA 1-IR
      were significantly higher in 2(nd) and 3(rd) trimesters while QUICKI was
      significantly lower in 2(nd) and 3(rd) trimesters of pregnancy when compared with
      controls. Also, mean FGIR was found to be significantly lower in 3rd trimester
      when compared with controls. CONCLUSION: As pregnancy advances, IR increases.
      Increased IR is associated with poor maternal and fetal outcome. Screening of all
      pregnancy for IR and early intervention may help to reduce the associated
      complications.

PMID- 25584209
TI  - Zinc status in type 2 diabetic patients: relation to the progression of diabetic
      nephropathy.
AB  - BACKGROUND AND OBJECTIVES: Zinc deficiency often occurs in patients with
      diabetes. Therefore, the relationship between zinc status and progression of
      nephropathy in diabetes has been explored. MATERIALS AND METHODS: Total 300
      diabetic patients and 100 non-diabetic healthy subjects (age matched) were
      selected followed by informed consent and divided into five groups as I: non
      diabetic normotensive control; II: diabetic normotensive; III: diabetic
      hypertensive; IV: diabetic normotensive with microalbuminuria; V: diabetic
      hypertensive with microalbuminuria. The blood samples of all subjects were
      collected and analyzed for serum zinc, serum creatinine, and estimated-glomerular
      filtration rate (e-GFR). Urine zinc, creatinine and microalbuminuria
      concentrations were determined. RESULTS: The serum zinc levels were low (p<0.01)
      in diabetic patients as compared to non-diabetic control subjects. The lower
      levels (p<0.001) of serum zinc were observed in Group IV and V as compared to
      group I-III. Significantly low levels of e-GFR (p<0.05) and high levels of
      microalbuminuria (p<0.001) were observed in diabetic patients with low serum zinc
      level as compared to normal serum zinc level. Serum zinc level in diabetic
      patients was inversely correlated with serum creatinine(r=-0.331, p<0.001),
      microalbuminuria (r=-0.587, p<0.001) and positively with e-GFR (r=0.194, p<0.01).
      CONCLUSION: It is evident from this study that advancing diabetic nephropathy
      represented by decreasing GFR and increasing microalbuminuria is associated with
      lower serum zinc levels. It thus indicates the need for determining serum zinc
      levels and the effectiveness of zinc supplementation in diabetic patients,
      particularly during the assessment of kidney damage.

PMID- 25584210
TI  - Study of serum sodium and potassium in acute myocardial infarction.
AB  - OBJECTIVES: Acute myocardial infarction (AMI) is one of the leading causes of
      morbidity and mortality across the world. Serum electrolytes changes in AMI have
      not been studied extensively and there is paucity of information in the
      literature in this regard. Scanty information is available in the literature
      about prognostic value of serum electrolytes in ischaemic heart disease. Hence
      this study was undertaken to study any changes in the serum electrolytes with
      special reference to serum sodium and potassium in cases of AMI and study the
      correlation of serum sodium and potassium in the severity and outcome of AMI.
      MATERIALS AND METHODS: Hundred people were included in study divided equally in
      study and control groups. Study group comprised confirmed diagnosis of recent
      onset of AMI. The blood samples of both the groups were analysed for Serum
      electrolytes (Na+, K+) by flame-photometry (Bio-Lab Diagnostic kit). RESULTS:
      There was statistically significant decrease in sodium and potassium levels in
      across all age groups & in both sexes of study group compared to control group.
      Significant high level of sodium was observed in AMI patients who are smokers and
      AMI patients with Diabetes whereas the level was low in AMI patients with
      hypertension. Potassium levels were low in AMI patients with Diabetes whereas the
      change was insignificant in association with smoking and hypertension.
      CONCLUSION: Decrease in sodium level was due to hypoxia and ischaemia, which
      increase the permeability of sarcolemma to sodium whereas decrease in potassium
      level was influenced by the catecholamine levels which are elevated in early
      acute myocardial infarction.

PMID- 25584211
TI  - Diagnostic utility of heat stable alkaline phosphatase in hypertensive disorders
      of pregnancy.
AB  - BACKGROUND: Hypertensive disorders in pregnancy (HDP) complicate 3-10% of all
      pregnancies. Though there are several biochemical parameters which aid in
      predicting hypertension of pregnancy, human placental alkaline phosphatase
      (PLAP), synthesized in placenta during pregnancy by placental
      syncytiotrophoblast, assumes diagnostic relevance. The purpose of this study was
      to compare the total alkaline phosphatase (ALP) and heat stable placental
      alkaline phosphatase (PLAP) levels in the serum of normotensive and hypertensive
      disorders of pregnancy and to evaluate the clinical utility of ALP and PLAP as a
      reliable, sensitive, specific and economical biochemical marker of HDP. MATERIALS
      AND METHODS: This was a case control study, carried out on pregnant women with
      hypertension, of south Indian population. Study included pregnant women, 60
      patients with hypertension and 60 controls. Biochemical assays were carried out
      by the IFCC approved procedures based on spectrophotometric method and using
      fully automated random access chemistry analyser. Data was compared by using
      student t-test. ROC was drawn to find out optimum cut off for ALP, PLAP and
      PLAP/ALP ratio in HDP. Pearson's correlation was performed to ascertain the
      association among markers. RESULTS: Serum total ALP, PLAP and PLAP/ALP ratio
      levels were significantly higher in hypertensive pregnant women when compared to
      controls (p<0.05). There was significant correlation among ALP, PLAP and DBP. ROC
      analysis of ALP (169.5), PLAP (69) and PLAP/ALP (0.44) ratios showed optimum cut
      offs in diagnosis of hypertension in pregnancy. CONCLUSION: Serum heat stable ALP
      isoenzyme and PLAP/ALP ratio could be useful adjuvant markers in diagnosis of HDP
      in association with other relevant and economically viable biochemical tests.

PMID- 25584197
TI  - Plasmid-mediated quinolone resistance.
AB  - Three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been
      discovered since 1998. Plasmid genes qnrA, qnrB, qnrC, qnrD, qnrS, and qnrVC code
      for proteins of the pentapeptide repeat family that protects DNA gyrase and
      topoisomerase IV from quinolone inhibition. The qnr genes appear to have been
      acquired from chromosomal genes in aquatic bacteria, are usually associated with
      mobilizing or transposable elements on plasmids, and are often incorporated into
      sul1-type integrons. The second plasmid-mediated mechanism involves acetylation
      of quinolones with an appropriate amino nitrogen target by a variant of the
      common aminoglycoside acetyltransferase AAC(6')-Ib. The third mechanism is
      enhanced efflux produced by plasmid genes for pumps QepAB and OqxAB. PMQR has
      been found in clinical and environmental isolates around the world and appears to
      be spreading. The plasmid-mediated mechanisms provide only low-level resistance
      that by itself does not exceed the clinical breakpoint for susceptibility but
      nonetheless facilitates selection of higher-level resistance and makes infection
      by pathogens containing PMQR harder to treat. 

PMID- 25584212
TI  - The serum levels of malondialdehyde, vitamin e and erythrocyte catalase activity
      in psoriasis patients.
AB  - BACKGROUND: Psoriasis is a common skin disease which is characterized by
      increased epidermal proliferation and dermal inflammation affecting 0.1-3% of
      general population. Most of the psoriasis patients are young or middle aged
      adults, although no age exempted. The oxidative stress develops due to imbalance
      in oxidants and antioxidants, which was proposed to have role in psoriasis. AIMS
      AND OBJECTIVES: The presented research work was planned to evaluate oxidative
      stress by measuring serum malondialdehyde (MDA) as oxidant and serum vitamin E,
      erythrocyte catalase (CAT) activity as antioxidants in psoriasis patients.
      MATERIALS AND METHODS: Total 90 clinically diagnosed psoriasis patients of age
      group of 20 to 60 years and without any drug therapy for preceding two months and
      90 matched healthy controls were included in the presented study. The severity of
      psoriasis was determined by PASI score. The fasting blood sample collected and
      accessed for serum MDA, serum vitamin E and erythrocyte catalase activity.
      RESULTS: The study results were compiled and statistical analysis was done using
      students t-test. Our results showed significantly increased levels of serum MDA
      (p<0.001) and significantly decreased serum vitamin E (p<0.001) as well as
      erythrocyte catalase activity (p<0.001) in psoriasis patients as compared to
      controls. CONCLUSION: The presented study concluded the oxidative stress in
      psoriasis, indicated by increased serum MDA and decreased Vitamin E, erythrocyte
      catalase activity. Our study also supports the possibility of involvement of
      oxidative stress in pathogenesis of psoriasis.

PMID- 25584213
TI  - XRCC-1 Gene Polymorphism (Arg399Gln) and Susceptibility to Development of Lung
      Cancer in Cohort of North Indian Population: A Pilot Study.
AB  - BACKGROUND: Smoking has been considered to be the major cause of lung cancer.
      However, only a fraction of cigarette smokers develop this disease. This suggests
      the importance of genetic constitution in predicting the individual's
      susceptibility towards lung cancer. This genetic susceptibility may result from
      inherited polymorphisms in genes controlling carcinogen metabolism and repair of
      damaged deoxyribonucleic acid (DNA). These repair systems are fundamental to the
      maintenance of genomic integrity. X-ray repair cross complimenting group I
      (XRCC1), a major DNA repair gene in the base excision repair (BER) pathway. It is
      involved in repair by interacting with components of DNA at the site of damage.
      Inconsistent results have been reported regarding the associations between the
      Arg399Gln polymorphism of XRCC1. This study demonstrates the importance of
      recognition of this relationship of lung carcinoma and genetic constitution of
      the person which will help guide clinicians on the optimal screening of this
      disease. AIM: To assess the role of XRCC1 gene polymorphism (Arg399Gln) directly
      on the variation in susceptibility to development of lung cancer in North Indian
      subjects. MATERIALS AND METHODS: One hundred males with diagnosed cases of lung
      cancer were recruited from Delhi State Cancer Institute (DSCI). Hundred healthy
      volunteers were taken as controls. DNA isolation was done and Polymerase chain
      reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) procedure undertaken
      to amplify the region containing Arg/Gln substitution at codon 399 (in exon 10).
      RESULTS: XRCC1 gene polymorphism is associated with increased risk of lung cancer
      when the Arg/Arg genotype was used as the reference group. The Arg/Gln and
      Gln/Gln was associated with statistically increased risk for cancer. CONCLUSION:
      Arg399Gln polymorphism in XRCC1 gene polymorphism is associated with lung cancer
      in North Indian subjects and screening for this polymorphism will help in
      targeting predisposed individuals and its prevention.

PMID- 25584214
TI  - Detection of Salmonella in Blood by PCR using iroB gene.
AB  - BACKGROUND: Salmonella, a genus of more than 2500 serological variants
      (serovars), includes many organisms that can cause human disease. Enteric fever
      remains an important public health problem in developing countries. Non typhoidal
      Salmonella generally produce a self limited gastroenteritis in healthy
      individuals whereas in extremes of age and immunocompromised cause severe fatal
      disease. The protean manifestations make this disease a true diagnostic
      challenge. AIM: The present study was carried out to optimize PCR for detecting
      the Salmonella genus using iroB gene and evaluate its use in the rapid diagnosis
      of typhoid and non typhoidal salmonellosis. MATERIALS AND METHODS: The study was
      carried out between August 2009 and July 2011 on blood samples from patients
      attending JIPMER hospital, Pondicherry, India with clinical suspicion of enteric
      fever and salmonellosis. Whole blood was used DNA extraction and conventional PCR
      done with iroB and fliC primers. Blood culture and Widal test were performed for
      all the patients. STATISTICAL ANALYSIS: Performed using Fischer's exact test with
      Graphpad Instat 3. RESULTS: PCR results were compared with blood culture.
      Sensitivity and specificity of PCR with fliC gene are 95.6% and 93.3%
      respectively. Sensitivity and specificity of PCR with iroB gene are 96.6% and
      93.3% respectively CONCLUSION: With iroB gene, additional cases of Salmonella
      Paratyphi A and non typhoidal Salmonella were detected when compared to fliC
      gene.

PMID- 25584215
TI  - A Comparison of Microscopy and Enzyme Linked Immunosorbent Assay for Diagnosis of
      Giardia lamblia in Human Faecal Specimens.
AB  - BACKGROUND: Giardia lamblia, a flagellate protozoa, is a common causative agent
      of parasitic diarrhoeal diseases of humans. Laboratory diagnosis mainly consists
      of direct microscopic examination of stool specimen for trophozoite and cysts of
      Giardia. However, due to intermittent faecal excretion of parasite, the case may
      be miss diagnosed and the patient may continue excreting the parasite and
      infecting others. Therefore, other mode of diagnosis should be looked for, which
      overcome the above drawbacks of microscopy used alone for diagnosis. OBJECTIVES:
      The present study was done to evaluate the efficacy of RIDASCREEN Giardia (ELISA)
      test in comparison to direct microscopy in the diagnosis of Giardia lamblia in
      stool specimens from patients with diarrhea and other gastrointestinal symptoms.
      MATERIALS AND METHODS: A total of 1680 patients were included in the study and
      three faecal specimens were taken from each patient which was divided into two
      parts. One part was used for direct wet mount examination and second part was
      used to put ELISA by using RIDASCREEN Giardia test. RESULTS: Out of 1680 stool
      samples, 380 specimens (22.6%) were found to be positive for Giardia lamblia.
      Maximum cases were detected by RIDASCREEN Giardia (ELISA) test with sensitivity
      of 100% and specificity of 91.5%. Maximum cases of giardiasis were detected in
      children less than 10 y of age (12.8%). CONCLUSION: RIDASCREEN Giardia test is a
      rapid and effective method with high sensitivity and specificity and detects
      Giardia antigens in stool specimens even when the count of parasite is low, thus
      reducing the chances of missing even the asymptomatic cases.

PMID- 25584216
TI  - Comparison of ELISA and Microscopy for detection of Cryptosporidium in stool.
AB  - BACKGROUND: Cryptosporidiosis, a diarrheal disease caused by the protozoan
      parasite Cryptosporidium spp. has become recognized as one of the most common
      causes of water borne diseases in humans. AIMS AND OBJECTIVES: To compare the
      sensitivity of ELISA and Microscopy for detection of Cryptosporidium in stool
      samples Materials and Methods: The study was conducted in the Department of
      Microbiology of PT. B.D. Sharma PGIMS Rohtak, between January 2011 to june 2011
      on 50 stool samples, which were processed for detection of cryptosporidial
      antigen by ELISA and detection of cysts by microscopy (Modified Ziehl and Nelsen
      staining). STUDY AND DESIGN: This was a prospective study conducted in the
      Department of Microbiology in PT. BD Sharma, PGIMS, Rohtak, India. RESULT: Out of
      total, 50 stool samples eighteen (36%) samples were found positive for
      Cryptosporidium cysts by microscopy in comparison to 3(6%) stool samples which
      were found positive for cryptosporidial antigen by ELISA. Samples found positive
      with ELISA were also positive with microscopy. Sensitivity, specificity, positive
      predictive value and negative predictive value for ELISA was 16.7%, 100%, 100%
      and 68% respectively. CONCLUSION: The study concludes that stool microscopic
      Modified acid fast staining is more sensitive method than ELISA for detection of
      Cryptosporidium in stool samples but the specificity of ELISA was more than
      microscopy.

PMID- 25584217
TI  - Mix-infection of S. Typhi and ParaTyphi A in Typhoid Fever and Chronic Typhoid
      Carriers: A Nested PCR Based Study in North India.
AB  - INTRODUCTION: Enteric fever is a systemic disease caused by Salmonella organism
      such as serotypes Typhi and ParaTyphi A, B, C. Salmonella ParaTyphi A contributes
      more than 50% of all the enteric fever cases and it has recently been projected
      as an emerging pathogen. MATERIALS AND METHODS: The present study was aimed to
      detect Salmonella Typhi and ParaTyphi A in urine, blood and stool specimens
      collected from cases of enteric fever (110), chronic typhoid carriers (46) and
      healthy controls (75) to explore the possibility of mixed infection by nested
      PCR. A new nested PCR primer was designed targeting putative fimbrial protein
      (stkG) gene which is one of the fimbrial gene families to Salmonella ParaTyphi A
      and for S. Typhi already reported primers targeting flagellin (fliC) gene.
      RESULTS: Large volume of urine specimens (15 ml) was found to be the best for
      detection of Salmonella serotypes. The urine sample was found to have mixed
      infection by both the serotypes in 40.9% of the cases but lower in blood (27.3%)
      and stool (13.6%). CONCLUSION: The present study concludes that occurrence of
      mixed infection may be quite frequent in typhoid and chronic typhoid carriers'
      individuals, although the reported recent rise in ParaTyphi A incidence may not
      be real.

PMID- 25584218
TI  - Comparison Between Virulence Factors of Candida albicans and Non-Albicans Species
      of Candida Isolated from Genitourinary Tract.
AB  - BACKGROUND: Candida spp. is frequently isolated from cases of vulvovaginal
      candidiasis and catheter associated UTI. C.albicans is the most frequently
      isolated species but non-albicans species of candida are gaining clinical
      significance. OBJECTIVES: To compare the virulence factors like biofilm
      production, phospholipase and hemolytic activity in C.albicans with that of non
      albicans species of candida isolated from urogenital tract. MATERIALS AND
      METHODS: Vaginal swabs and urine samples received in Microbiology laboratory
      during one year period were processed by standard methods. The candida isolates
      were speciated and biofilm production, phospholipase and hemolytic activity were
      studied in them. Statistical analysis was performed using SPSS version 11.5.
      RESULTS: Out of the 3001 urine samples processed 41 (1.3%) were positive for
      candida, out of 293 high vaginal swabs 41(14%) were positive for candida.
      C.albicans was the most prevalent isolate followed by C.tropicalis, C.glabrata
      and C.krusei. Out of 40 C.albicans strains, 22 (55%) produced biofilm, 39 (97.5%)
      produced hemolysin and 21 (52.5%) produced phospholipase. Out of 42 strains of
      non albicans species of candida, 19 (45%) produced biofilm, 41(97.6%) hemolysin
      and 5 (12%) produced phospholipase. CONCLUSION: Phospholipase production was
      better in C.albicans in comparison toother species of candida. There was no
      statistically relevant difference between hemolysin and biofilm production by
      C.albicans and non albicans strains of candida.

PMID- 25584219
TI  - Comparison of various methods used to detect biofilm production of Candida
      species.
AB  - PURPOSE: The biofilm of organisms can be considered as a virulence factor because
      of the resistance towards antimicrobial agents. Formation of Candida biofilms are
      observed in blood, mucosal surface and most medical devices i.e. nonliving
      objects in patient's body. The study was undertaken to conclude the most
      sensitive and specific test for detection of biofilm formation. MATERIALS AND
      METHODS: Quantitative measurement of biofilm formation was assessed by three
      methods- 1) XTT reductionassay, 2) Percentage Transmission (%T) and 3) Crystal
      Violet assay in microtitre plate for 425 Candida isolates. RESULTS: Out of 425
      Candida strains, XTT reduction assay gave 72 Biofilm positive strains accounting
      for 16.94 %. The percentage transmission (% T) method gave 56 strains Biofilm
      positive (13.17 %) and Crystal violet assay gave 50 positive strains (11.76 %).
      Compared to Percentage Transmission (% T) and Crystal violet method, XTT
      reduction assay gave maximum percentage of Biofilm positivity. CONCLUSION: In
      comparison of 3 methods used for detection of biofilm formation, XTT reduction
      assay was the most sensitive and specific method.

PMID- 25584220
TI  - Antimicrobial activity and stability of electron beam irradiated dental
      irrigants.
AB  - BACKGROUND: The electron beam (e-beam) radiation is considered as an effective
      means of sterilization of healthcare products as well as to induce the structural
      changes in the pharmaceutical agents/drug molecules. In addition to structural
      changes of pharmaceutical it also induces the formation of low molecular weight
      compounds with altered microbiological, physicochemical and toxicological
      properties. Among the several known medicaments, sodium hypochlorite (NaOCl) and
      chlorhexidine digluconate (CHX) are used as irrigants in dentistry to kill the
      pathogenic microorganisms like Enterococcus faecalis, Staphylococcus aureus,
      Streptococcus mutans and Candida albicans inhabiting the oral cavity. OBJECTIVES:
      The aim of this study was to evaluate the antimicrobial activity and stability of
      e-beam irradiated dental irrigants, NaOCl and CHX. MATERIALS AND METHODS: Two
      dental irrigants NaOCl (1.25% and 2.5%) and CHX (1% and 2%) were exposed to
      various doses of e-beam radiation. The antimicrobial activities of e-beam
      irradiated irrigants were compared with the non-irradiated (control) irrigants
      against E. faecalis, S. aureus, S. mutans and C. albicans by disc diffusion
      method. Following the storage, physico-chemical properties of the irrigants were
      recorded and the cytotoxic effect was evaluated on human gingival fibroblast
      cells. RESULT: The irrigants, 1.25% NaOCl and 1% CHX showed significantly
      increased antimicrobial activity against both E. faecalis, (16+0.0) and S. aureus
      (25+0.0) after irradiation with 1 kGy e-beam. Whereas, 2.5% NaOCl and 2% CHX
      showed slightly increased antimicrobial activity only against S. aureus (28+0.0).
      The significant difference was noticed in the antimicrobial activity and
      cytotoxicity of irradiated and non-irradiated irrigants following the storage for
      180 d at 4(0)C. CONCLUSION: The e-beam irradiation increased the antimicrobial
      activity of irrigants without altering the biocompatibility.

PMID- 25584221
TI  - Evaluation of chromogenic media in detection of vancomycin resistant enterococci.
AB  - INTRODUCTION: Vancomycin resistant Enterococci have become important nosocomial
      pathogens. So it is necessary to monitor continuously such infections in the
      hospitals. MATERIALS AND METHODS: A total of 100 Enterococci isolated from 4489
      various clinical samples were speciated and antibiogram was done according to
      standard laboratory methods. The efficacy of CHROMagar(TM) VRE (France) and
      Hicrome VRE (Himedia) in detecting VRE was evaluated using E- test (Himedia).
      RESULTS: Hicrome VRE and CHROMagar(TM) VRE showed sensitivity of 100% and
      specificity of 99% as compared to E-test. CONCLUSION: In the present study VRE
      was not isolated. Prudent use of vancomycin and continuous surveillance for VRE
      will prevent the emergence of vancomycin resistant Enterococci in the locality in
      future. Identification of VRE by chromogenic media is rapid, easy to perform,
      cost effective compared to technically demanding, time consuming and costly
      conventional method.

PMID- 25584222
TI  - A fatal case of fungal empyema due to Candida krusei and Candida tropicalis: a
      rare occurrence with an atypical presentation.
AB  - Infections of the pleural cavity remain an important cause of morbidity and
      mortality despite advancement in diagnostic modalities and therapy. Community
      acquired empyema thoracis due to Candida species are rarely reported in
      paediatric literature. We hereby report an interesting case of empyema due to co
      infection of Candida krusei with Candida tropicalis. A 11-year-old female child
      presented with respiratory distress. Chest X-ray showed massive pleural effusion,
      thoracocentesis showed it as purulent exudate and she was empirically treated
      with antibiotics. C. tropicalis and C. krusei were isolated from the pus sample
      proving to be fungal empyema. Inspite of antifungal agents and mechanical
      ventilation, her general condition rapidly deteriorated and she succumbed. 

PMID- 25584223
TI  - Neonatal septicaemia caused by vancomycin resistant enterococcus faecium-a case
      report.
AB  - Neonatal bacterial sepsis is one of the major causes of morbidity and mortality
      in neonates. 10% cases of neonatal bacteraemia and septicaemia are caused by
      Enterococci. The increasing incidence of Vancomycin resistant enterococci (VRE)
      is of particular concern because of limited treatment options and increased
      mortality. We report here a case of neonatal sepsis in a premature baby caused by
      vancomycin resistant Enterococcus faecium Van A phenotype from a tertiary care
      Hospital in South India. A preterm baby boy with low birth weight was admitted to
      the NICU with Respiratory distress and meconium aspiration. On 5(th) day the baby
      succumbed to death and a final diagnosis of respiratory distress and meconium
      aspiration with sepsis was made. Blood cultures sent yielded vancomycin resistant
      Enterococcus faecium (minimum inhibitory concentration >= 256 MUg/ml). It was
      confirmed as Enterococcus feacium Van A phenotype by Automated Vitek system. 

PMID- 25584224
TI  - Isolation, Identification and Antimicrobial Susceptibility of Anaerobic Bacteria:
      A Study Re-emphasizing Its Role.

PMID- 25584225
TI  - Value of bone marrow imprint smears in early diagnosis of bone marrow
      pathologies.
AB  - BACKGROUND: Examination of bone marrow plays a pivotal role in the practice of
      haematology. It can be evaluated by three ways-bone marrow aspiration (BMA), bone
      marrow touch imprints (BMI) and bone marrow biopsy (BMBx). AIM AND OBJECTIVE: To
      study the efficacy and reliability of BMI smears in comparison to BMA smears, in
      making a diagnosis of diseases involving bone marrow. Setting and Designs: This
      study was carried out in the Department of Pathology, Institute of Medical
      Sciences, Varanasi over a period of 26 months. MATERIALS AND METHODS: A total
      number of 182 cases, with their BMA, BMI and BMBx samples (from each and every
      case), were evaluated and their findings even compared. STATISTICAL ANALYSIS: All
      the observations were evaluated using simple and basic statistical tool, i.e.
      percentage. RESULTS: The cellularity or cell density on BMI correlated with the
      cellularity of BMBx in 78.6% cases, which was higher than the value observed with
      BMA smears (71.4%). The spreading quality was better and cytological details were
      better appreciated in BMI as compared to BMA. Also, the presence of
      lymphoglandular bodies and particles on BMI were additive diagnostic clues. All
      of those findings were reflected in the higher diagnostic accuracy of BMI than
      BMA. CONCLUSION: BMI should be a standard practice and be considered as an early
      and reliable diagnostic tool for evaluating bone marrow pathologies.

PMID- 25584226
TI  - Clinico-pathological Study of Space Occupying Lesions of Nasal Cavity, Paranasal
      Sinuses and Nasopharynx.
AB  - BACKGROUND: A variety of non-neoplastic and neoplastic lesions of nasal cavity,
      paranasal sinuses and nasopharynx are commonly encountered in clinical practice.
      The aim of this study was to study clinical and histopathological profile of
      space occupying lesions of nasal cavity, paranasal sinuses and nasopharynx in a
      tertiary care hospital of Rajasthan over the period of January 2013 to January
      2014. MATERIALS AND METHODS: This was a prospective study of 147 cases (male 100,
      female 47; age group ranging from less than 1 y to 76 y) of space occupying
      lesions of nasal cavity, paranasal sinuses and nasopharynx over the period of 12
      months (from January 2013 to January 2014). All tissues after fixation in 10%
      buffered formalin, processed and then stained with Hematoxylin & Eosin to study
      various histopathological patterns. RESULTS: These 147 cases were broadly
      categorized in two categories, one category as nasal and paranasal sinus masses
      and the other as nasopharyngeal masses with 91 and 56 cases, respectively. These
      lesions were common in second and third decades of life with male predominance.
      Among nasal and paranasal sinus masses, there were 67 (73.6%) non-neoplastic and
      24 (26.4%) neoplastic lesions. Inflammatory polyps (89.5%) were the most common
      among the non-neoplastic masses; Inverted papilloma (45.46%) the most common
      among the benign neoplastic and squamous cell carcinoma (46.15%) was the
      commonest out of all malignant masses. Out of 56 nasopharyngeal masses, there
      were 53 (94.6%) non neoplastic and 3 (5.4%) neoplastic lesions. Majority of these
      i.e. 52 cases were of adenotonsillar hypertrophy. CONCLUSION: We concluded that
      complete clinical, radiological and histopathological correlation helps us to
      categorize these sinonasal lesions into various non-neoplastic and neoplastic
      types. But final histopathological examination provides a confirmatory diagnosis,
      although Immunohistochemistry is the final diagnostic method in few cases.

PMID- 25584227
TI  - Colorectal cancer: a study of risk factors in a tertiary care hospital of north
      bengal.
AB  - AIM: Age, sex, living place (urban or rural), smoking, alcohol consumption,
      dietary pattern, obesity are considered as risk factors for Colorectal cancer.
      Our study was done to evaluate the association between these risk factors and
      colorectal cancer in the population of North Bengal. MATERIALS AND METHODS: The
      present study was done over a period of one year as a hospital-based analytical
      observational type of study with cross-sectional type of study design. All the
      patients undergoing colorectal endoscopic biopsy at the Department of Surgery,
      NBMC&H during the study period for various clinical indications comprised the
      study population. History and clinical examination were done of the patients
      whose colorectal biopsy were taken and filled-up in a pre-designed pre-tested
      proforma. Significance was tested at 95% confidence interval. RESULTS: There is
      an increased risk of colorectal carcinoma (CRC) with increasing age in our study
      population. Odd's ratio for last 2 age groups are statistically significant with
      2.83 for 41-50 years age group (95% CI is0.3-24), 13.6 for 51-60 years age group
      (95% CI is 2.1-85.9), 42.5 for more than 60 y age group patients (95% CI is 3.1
      571). There is increased risk of colorectal carcinoma in males with an Odd's
      ratio of 1.6 (95% CI is 0.5-5.5), but it is not statistically significant. There
      was an increased urban incidence of colorectal carcinoma compared to rural
      population with an Odd's ratio of 1.8 (with a 95% CI of 0.6-5.9). In our study
      smoking also proved to be a risk factor and it is significant with an Odd's ratio
      of 5.4 with a 95% CI of 1.6-8.7. Odd's ratio for cases of alcohol consumption was
      3.5 with a 95% CI of 1-11.6. Carcinoma cases were more common among patients with
      history of non-vegetarian dietary intake with Odds ratio of 1.5 (with a 95% CI of
      0.3-8.7), but it was not statistically significant. Obesity has got a significant
      association with CRC in our study with an Odd's ratio of 7.2 (with 95% CI of 1.3
      40.2). CONCLUSION: More than 50 years of age, smoking, obesity were significant
      risk factors in our study. Other risk factors were though not significant, but
      much more common in colorectal cancer patients compared to non-malignant
      population.

PMID- 25584228
TI  - To evaluate the role of bone marrow aspiration and bone marrow biopsy in
      pancytopenia.
AB  - BACKGROUND: Pancytopenia is not a disease entity but a triad of findings that may
      result from various disease processes, primarily or secondarily involving the
      bone marrow. Bone marrow aspiration and biopsy evaluation along with good
      clinical correlation is of utmost importance to evaluate the causes of
      pancytopenia and planning further investigations. AIMS: The present study was a
      prospective clinicohaematological study undertaken to analyse the various causes
      of pancytopenia by evaluating bone marrow aspiration and biopsy and correlating
      with clinical findings, complete blood counts and peripheral blood picture.
      MATERIALS AND METHODS: Fifty patients of pancytopenia were included in the study
      in which relevant history and physical examination findings were recorded. Bone
      marrow aspiration and biopsy were performed simultaneously in all cases. Perl's
      stain was done in all cases and special stains like MPO, PAS and reticulin were
      also done wherever necessary. RESULTS AND CONCLUSION: The maximum cases of
      pancytopenia were in the age group of 10 to 30 y with male preponderance.
      Aplastic anaemia was found to be the most common aetiology of pancytopenia
      followed by normoblastic erythroid hyperplasia, megaloblastic anaemia, acute
      leukemias, myelofibrosis, lymphoid neoplasia and iron deficiency anaemia. It was
      concluded from the study that although the advantages of bone marrow aspiration
      and biopsy differ, both are complimentary to each other and should be performed
      simultaneously for a complete bone marrow work up and evaluation. It is only
      through the correlation of clinical, hematological and bone marrow examination
      findings that proper evaluation and management of patients of pancytopenia can be
      made.

PMID- 25584229
TI  - Evaluation of Pre-Malignant and Malignant Lesions in Cervico Vaginal (PAP) Smears
      by Nuclear Morphometry.
AB  - BACKGROUND: Cervical cancer is the second most common cancer occurring among
      women worldwide, with almost half a million new cases each year. Normal cells
      gradually transform to form cancer cells through several stages. So, the changes
      occurring during the transformational stages need to be assessed. AIM: Our aim
      was to study various nuclear parameters useful in evaluating pre-malignant and
      malignant cervico-vaginal pap smears. MATERIALS AND METHODS: Bethesda System was
      used to categorize cervical pap smears into premalignant and malignant lesions.
      Nuclear parameters were calculated using J 1.44C morphometric software. Several
      nuclear size parameters were analysed. RESULTS: The nuclear area, perimeter,
      diameter were found to be statistically significant (p<0.05) parameters in
      differentiating premalignant from malignant cervical smears. CONCLUSION: Nuclear
      morphometry was thus a useful objective tool in differentiating premalignant from
      malignant cervical smears.

PMID- 25584230
TI  - Primary MPNST in Childhood- A Rare Case Report.
AB  - Malignant peripheral nerve sheath tumour usually occurs between 20-50 years of
      age, comprising about 5-10% of soft tissue sarcomas. Only 1.7% of them have been
      reported to occur in children < 5 months of age according to the literature.
      Here, we are describing 18 mnth old male child presented with a swelling in the
      lower back. MRI showed a sacrcoccygeal swelling extending to and communicating
      with CSF at lower sacral level. Birth history of the child was normal with normal
      apgar score. The histological diagnosis was malignant peripheral nerve sheath
      tumour. IHC showed focal positivity of GFAP and S100. Primary spinal MPNST in
      children are rarer. A careful neurological examination is warranted in children.
      Early diagnosis and referral to multidisciplinary team are important in ensuring
      the best diagnosis and optimal therapy in this young age. 

PMID- 25584231
TI  - Mixed malignant germ cell tumour of third ventricle with hydrocephalus: a rare
      case with recurrence.
AB  - Malignant Germ Cell Tumours (GCTs) are rare, accounting for 3% of intracranial
      tumours and just like their extracranial counterparts represent a wide array of
      disease. Combination of Germinoma with Teratoma is very rare. Here in, we
      describe a case of Mixed Malignant Germ cell tumor of third ventricle with
      recurrence with emphasis on histopathological and radiological findings. 

PMID- 25584232
TI  - Extra- adrenal silent retroperitoneal paraganglioma: report of a rare case.
AB  - Extra- adrenal retroperitoneal paragangliomas are extremely rare neuroendocrine
      neoplasms with an incidence of 2-8 per million. They arise from embryonic neural
      crest cells and are composed mainly of chromaffin cells located in the para-
      aortic sympathetic chain. They synthesize, store and secrete catecholamines
      because of which they may present with headache, sweating, palpitation and
      symptoms of hypertension. On the other hand, they may remain silent and non-
      functional and present with vague symptoms like pain abdomen due to episodic
      release of catecholamines. Histologically and immunohistochemically, non-
      functional and the functional tumours are no different from each other. Primary
      methods of pre-operative diagnosis include imaging techniques which also help in
      surgical planning and pre-operative preparation. Non- functional tumours of ten
      escape pre-operative detection and create per- operative complications. We
      present a case of non- functional extra- adrenal retroperitoneal paraganglioma
      occurring in a 66-year-old female patient presenting with pain and mass per
      abdomen. On ultrasonongraphy, a retroperitoneal mass of probable mesenchymal
      origin was suspected. The patient was posted for surgical resection of the mass.
      Per-operatively, the patient developed hypertensive crisis and massive bleeding.
      Post-operatively she developed renal failure and succumbed to it after three
      days. This report highlights the importance of pre- operative diagnosis which is
      vital in the management of extra- adrenal retroperitoneal paraganglioma. 

PMID- 25584233
TI  - Fibromatosis colli - a rare cytological diagnosis in infantile neck swellings.
AB  - Fibromatosis colli or sternocleidomastoid tumour is a rare cause of benign neck
      mass in infants. It is a self limiting fibroblastic lesion usually presenting
      with torticollis and a history of birth trauma.It is one of the few causes in
      which Fine Needle Aspiration Cytology (FNAC) is indicated in a neonate to confirm
      the diagnosis and to differentiate it from other congenital, inflammatory and
      neoplastic causes. FNAC provides a rapid, cost-effective, reliable, non invasive
      method of diagnosis resulting in conservative management of these lesions. We
      present two interesting cases of neck swelling in infants where FNAC performed as
      the first diagnostic procedure was instrumental in establishing the diagnosis of
      fibromatosis colli thus avoiding unnecessary surgical intervention. 

PMID- 25584234
TI  - Waldenstroms Macroglobulinemia Patient Presenting with Rare 'lytic' Lesions and
      Hypercalcemia: A Diagnostic Dilemma.
AB  - Waldenstroms macroglobulinemia (WM) is an uncommon B-cell lymphoproliferative
      neoplasm characterized by lymphoplasmacytic cells infiltrating the Bone Marrow,
      along with demonstration of an IgM monoclonal gammopathy in the serum. Lytic
      lesions are considered one of the basis for differentiating a patient of Multiple
      Myeloma (MM) and WM. However, very few cases have been reported with a patient
      presenting with lytic lesions in a WM patient, thereby, complicating the disease.
      By finding the extent of these lytic lesions and bone involvement, Not only can
      we signify the presence or absence of bone lesions, but we can also direct the
      more efficient use of skeletal X-rays for documentation of the extent, location,
      and response of bone abnormalities to interventional chemotherapy and radiation
      therapy. Our case was mimicking the classic case of MM. Using the International
      Criteria for diagnosis for WM, diagnosis for MM was excluded and diagnosis for WM
      was made. After two weeks of therapy, the patient showed marked clinical
      improvement. 

PMID- 25584235
TI  - Persistent monotypic plasma cells with absence of neoplastic B cell component in
      a treated case of waldenstrom macroglobulinemia: a sign of residual disease?
AB  - Waldenstrom macroglobulinemia (WM) is a rare indolent variant of non- Hodgkin's
      lymphoma characterised by lymphoplasmacytic infiltration of bone marrow (BM)
      associated with a serum IgM paraprotein. The WHO classification states that the
      neoplastic cells of WM usually are positive for monotypic surface immunoglobulin
      light chain, IgM, CD19, and CD20 and are negative for CD5, CD10, and CD23. Serum
      monoclonal protein detection by serum protein electrophoresis and bone marrow
      aspirate and biopsy are required for WM diagnosis, monitoring and response
      assessment. Pathologist must dissuade themselves from making a hasty decision on
      calling a complete response in WM when neoplastic B cell component is absent.
      Evaluation of clonality of any residual plasma cells must be done in all cases of
      WM to evaluate the presence and extent of residual or persistent disease. Role of
      additional therapy targeted at these residual plasma cells in WM can be evaluated
      as tools for achieving complete remission. Herein, we present a case of WM with
      residual monotypic plasmacytosis in BM, without B lymphocytes after therapy. 

PMID- 25584236
TI  - Collision tumours of ovary: a very rare case series.
AB  - Collision tumours are composed of two histologically distinct neoplasms in the
      same organ without intermixture of cell types. Here the author present a case
      series of 4 cases of collision tumours of ovary with brief review of literature.
      Two cases have a combination of mucinous cystadenoma and teratoma whereas third
      case is a combination of serous papillary cystadenoma with teratoma and the
      fourth case has a combination of serous papillary cystadenocarcinoma and
      teratoma. The cases were diagnosed post-operatively. It is important to correctly
      diagnose the component of tumour for further management and favourable prognosis.

PMID- 25584238
TI  - A randomised trial comparing efficacy, onset and duration of action of pethidine
      and tramadol in abolition of shivering in the intra operative period.
AB  - INTRODUCTION: Regional anaesthesia (spinal anaesthesia) is widely used as a safe
      anaesthetic technique for both elective and emergency operations. Shivering is
      known to be a frequent complication, reported in 40 to 70% of patients undergoing
      surgery under regional anaesthesia. Various methods are available for the control
      of shivering during anaesthesia. Here we have compared Tramadol, a synthetic
      opioid with Pethidine, the gold standard drug for the treatment of shivering, in
      the quest for more safe and efficacious drug. MATERIALS AND METHODS: Forty
      patients of ASA 1 and 2 status posted for elective surgical procedures under
      neuraxial block were selected. Group P (n=20) received Pethidine 0.5mg/kg IV and
      group T (n=20) received tramadol 1.0 mg/kg IV. RESULTS: Both the drugs were found
      to be effective in reducing shivering. Nineteen patients in the Group T had
      control of shivering at end of 5 minutes but there were no patients who had
      control of shivering Group P (p < 0.0001) which is statistically significant.
      CONCLUSION: Tramadol reduced the occurrence of postanesthetic shivering more
      significantly than pethidine.

PMID- 25584237
TI  - Effect of different doses of dexmedetomidine as adjuvant in bupivacaine -induced
      subarachnoid block for traumatized lower limb orthopaedic surgery: a prospective,
      double-blinded and randomized controlled study.
AB  - BACKGROUND AND AIMS: Improved pain management for blunt trauma to the lower
      extremity has shown to reduce morbidity, induce early ambulation and improve long
      term outcomes. Dexmedetomidine; a selective alpha-2 agonist; has recently been
      used intrathecally in different doses to prolong spinal anaesthesia. We evaluated
      the effect of adding two different doses of dexmedetomidine to hyperbaric
      bupivacaine for spinal anaesthesia. The primary endpoints were the onset and
      duration of sensory, motor block and duration of analgesia. MATERIALS AND
      METHODS: Eighty patients, (20-60yrs) posted for elective lower limb orthopedic
      surgery of traumatic origin under spinal anaesthesia were divided into 2 equal
      groups (Group D5&D10) in a randomized, double-blind fashion. In this prospective
      parallel group study, group D5(n=40) 3ml 0.5% hyperbaric bupivacaine+5MUg
      dexmedetomidine in 0.5 ml of normal saline and group D10 (n=40) 3ml 0.5%
      bupivacaine+10MUg dexmedetomidine in 0.5 ml of normal saline were administered
      intrathecally. Sensory and motor block onset times and block durations, time to
      first analgesic use, total analgesic need, postoperative VAS, hemodynamics and
      side effects were recorded for each patient. RESULTS: Though with similar
      demographic profile in both groups, sensory and motor block in group D10(p<0.05)
      was earlier than group D5. Sensory, motor block duration and time to first
      analgesic use were significantly longer and the need for rescue analgesics was
      lower in group D10(p<0.05) than D5. 24 h VAS score was significantly lower in
      group D10(p<0.05). Intergroup hemodynamics was comparable (p>0.05) without any
      appreciable side effects. CONCLUSION: Spinal dexmedetomidine increases the
      sensory, motor block duration and time to first analgesic use, and decreases
      analgesic consumption in a dose-dependent manner.

PMID- 25584239
TI  - A rare case of adult acquired tracheo-oesophageal fistula with sub-glottic
      stenosis for corrective surgery- an anesthetic challenge.
AB  - Acquired trachea-esophageal fistula (TEF) is a rare condition in adults and
      causative factors include malignancy, trauma and various iatrogenic causes. The
      important causative factor of TEF in our case was percutaneous tracheostomy. The
      normal protective laryngeal reflexes are lost in TEF due to the patent tract from
      the airway to the upper gastrointestinal tract. The TEF poses a challenge for the
      surgeon and the anaesthesiologist, as the fistula lies in close proximity to
      oesophagus, trachea, upper mediastinal contents and large blood vessel. Here we
      present a rare case of anesthetic management of a 26 year old male patient with
      complaints of regurgitation of part of swallowed food particles through an in
      situ tracheostomy tube since two years. 

PMID- 25584240
TI  - Mannitol an adjuvant in local anaesthetic solution: recent concept & changing
      trends (review).
AB  - Various adjuncts have been utilized with lignocaine to decrement tourniquet pain
      and prolong postoperative analgesia and its efficacy during dental extraction and
      various other restorative procedures in dentistry. An obligatory part of the
      dental process is to sanction a patient to feel comfortable and pain-free during
      operational and remedial dental procedures. The most popular local anaesthetic
      injection for lower teeth is the inferior alveolar nerve (IAN) block. Instead of
      this the percentage of ineffectiveness is higher is inferior alveolar nerve block
      as compared to other local anaesthetic nerve block. The goal of cumulating
      different drugs is to engender the best therapeutic effects with the fewest or no
      unpropitious effects. There are fewer researches and evidence present which
      recommend and promote the application and effectiveness of mannitol other than in
      the administration in decreasing raised intracranial pressure. It is paramount to
      know how the drug interacts with each other to minimize the unexpected or
      perilous effects. 

PMID- 25584241
TI  - Potential Drug - Drug Interactions among Medications Prescribed to Hypertensive
      Patients.
AB  - CONTEXT: Drug-drug interactions(DDIs) are significant but avoidable causes of
      iatrogenic morbidity and hospital admission. AIM: To detect potential drug-drug
      interactions among medications received by hypertensive patients. MATERIALS AND
      METHODS: Patients of both sex and all adult age groups, who were attending
      medicine out -patient department (OPD) of a tertiary care teaching rural hospital
      since last six months and were being prescribed antihypertensive drug/s for
      essential hypertension, were selected for the study. Hypertensive patient with co
      morbities diabetes mellitus, ischemic heart diseases, congestive heart failure,
      and chronic renal diseases were also included in the study. Potential drug drug
      interactions were checked with medscape drug interaction software. RESULTS: With
      the help of medscape drug interaction software, 71.50% prescriptions were
      identified having atleast one drug-drug interaction. Total 918 DDIs were found in
      between 58 drug pairs. 55.23% DDIs were pharmacodynamic, 4.79% pharmacokinetic
      type of DDIs. 32.24% DDIs were found affecting serum potassium level. 95.42% DDIs
      were found significant type of DDIs. Drug drug interaction between atenolol &
      amlodipine was the most common DDI (136) followed by metoprolol and amlodine (88)
      in this study. Atenolol and amlodipine ( 25.92%) was the most common drugs to
      cause DDIs in our study. CONCLUSION: We detected a significant number of drug
      drug interaction in hypertensive patients. These interactions were between
      antihypertensive agents or between hypertensive and drug for co-morbid condition.

PMID- 25584242
TI  - Evaluation of efficacy and tolerability of cefotaxime and sulbactam versus
      cefepime and tazobactam in patients of urinary tract infection-a prospective
      comparative study.
AB  - OBJECTIVE: Urinary tract infection (UTI) is the third most common infection
      experienced by humans after respiratory and gastro-intestinal infections.
      Cephalosporins are now widely been used in UTI, but emerging resistance is a
      problem to that. Our study aims at evaluating efficacy and safety of third
      generation cephalosporin combined with beta lactamase inhibitors compared with
      fourth generation cephalosporin. MATERIALS AND METHODS: The present, open,
      randomised, parallel group comparative study includes 60 patients of urinary
      tract infection. Group A patient were put on treatment regimen of cefotaxime and
      sulbactam (0.5-2 gms IV/IM BD) and Group B patients were prescribed cefepime and
      tazobactam (0.5-1 gm IV/IM BD) depending upon urine culture and sensitivity
      pattern of causative agent and condition of the patient. Bacteriological cure
      rate, clinical cure rate will be assessed for efficacy and adverse drug reaction
      (ADR) recorded for evaluating safety. RESULTS: The study showed a male
      predominance with 37 males (61.6%) and 23 (38.4%) females out of the total 60
      patients with a maximum number within the age group of 50-70., and the most
      common organism isolated was E coli (73.3%), in rest of the patients Klebsiella
      (13.33%), Proteus (6.66%), and Staphylococcus (6.66%) were isolated. The overall
      bacteriological cure rate, in the present study, with cefotaxime/sulbactam and
      cefepime/tazobactam was 86.5%+/-6.5 and 93.3%+/-6.7 respectively. The clinical
      cure rate post five days of therapay, in goup A1 was 79.03%+/-2.82 and the same
      in group B1 was 87% +/- 2.11. The clinical cure rate post ten days of therapy in
      group A2 98.57+/-0.03 and the same in group B2was 100%. Overall success rate as
      evaluated by our data in the present study in group A i.e those treated with
      cefotaxime/sulbactam was 89.28+/-9.1% and in group B i.e. those treated with
      cefepime/ tazobactam and 94.49+/-5.06%. CONCLUSION: From the present study, those
      drugs in both generations of cephalosporins combined with beta lactamase
      inhibitors cefotaxime/sulbactam and cefepime/tazobactam were equally effective
      and well tolerated in the treatment of UTI. However the cost effectiveness and
      safety parameters are the important deciding factors for prescribing the same.

PMID- 25584244
TI  - Effect of atorvastatin on memory in albino mice.
AB  - OBJECTIVE: The aim and objective of the present study was to evaluate the effect
      of atorvastatin on learning and memory in albino mice. MATERIALS AND METHODS:
      Thirty Swiss albino mice were divided into 5groups (n=6). In group2, group4 and
      group5 hyperlipidemia was induced by high fat diet (HFD) orally for 28days.
      Atrorvastatin was given to group3, group4 and group5 orally for 14 d. Learning
      and memory was evaluated with Hebb Williams's maze, Elevated plus maze, Y maze
      and Step through latency. Continuous data were analyzed by one way ANOVA followed
      by Scheffe multiple range test, discrete data were analyzed by Kruskal - Wallis
      test. The level of significance was 5% (p <= 0.05). RESULT AND CONCLUSION: HFD
      treatment had shown significant increase in body weight, significant impairment
      in learning and memory (p < 0.05). Only atorvastatin treated group had shown
      better learning and memory in comparison to HFD group. Atorvastatin 10mg/kg and
      20 mg/kg had reversed the HFD induced impairment of learning and memory but there
      was no significant difference between the doses (p > 0.05).

PMID- 25584243
TI  - A study of utilization of antimicrobial agents in patients on ventilator in
      intensive care unit (ICU) at tertiary care teaching hospital, India.
AB  - OBJECTIVE: To study the use of antimicrobial agents in patients on ventilator in
      ICU. MATERIALS AND METHODS: Study was conducted at tertiary care teaching
      hospital Ahmedabad, India. Total 300 patients admitted in ICU and prescribed
      antimicrobial agents were included in the study. The data were recorded in
      preformed Case Record Form (CRF) and were analysed by Z and x(2) Test. RESULTS:
      Patients were divided into group A (patients on ventilator support) and group B
      (patients without ventilator support). In all the patients antimicrobial agents
      were prescribed empirically and more than two antimicrobial agents were
      prescribed in both groups. It was observed that above 60% antimicrobial agents
      were prescribed according to WHO, National and State Essential Medicine List
      (EML). Restricted antimicrobial agents (according to antimicrobial policy of
      tertiary care teaching hospital) were prescribed significantly (p<0.05) higher in
      group A as compared to group B. Resistance to antimicrobial agents by Pseudomonas
      aeruginosa and Kleibsella shown significantly (p<0.05) higher in group A as
      compared to group B. Change of antimicrobial therapy after Culture Sensitivity
      Test (CST) was significantly (p<0.05) higher in group A as compared to group B.
      CONCLUSION: Number of antimicrobial agents, antimicrobial resistance and change
      of antimicrobial therapy after CST were higher in patients on ventilator support.

PMID- 25584245
TI  - Hepatoprotective Role of Caesalpenia bonduc: A Histopathological and Biochemical
      Study.
AB  - BACKGROUND: Hepatotoxicity is one of the inevitable side effects of long term use
      of medicines in many different disorders, chronic use of alcohol and in certain
      infectious disorders. Even though there are few effective drugs to treat such
      hepatotoxicity, mortality due to hepatotoxicity is increasing day by day.
      Therefore, in search of alternative and more effective medicine we found that
      Caesalpenia bonduc (CB), a shrub grows in hotter places of south Asia has been
      effectively used to treat such hepatotoxicity in folk medicine. AIM: AIM of the
      study is to scientifically evaluate the hepatoprotective nature of aqueous
      extract of CB using Carbon tetrachloride(CCl4) induced hepatotoxic rat model.
      Materials and Methods and Result: Elevated levels of blood ALT, AST and ALT
      enzymes were found in CCl4 induced hepatotoxic rat models. Treating these animals
      with CB either prior or after the induction of hepatotoxicity, shows significant
      decrease in the levels of ALP, AST, and ALT in their blood in comparison with the
      untreated hepatotoxic group. Additionally, histologically, hepatotoxic rats show
      necrotic changes & vacuolation in their hepatocytes, altered hepatic architecture
      and congested hepatic sinusoids. However, such histopathological adverse changes
      were minimized when these animals treated with CB. CONCLUSION: Results of the
      present study indicate that CB acts as both preventive and curative
      hepatoprotector.

PMID- 25584246
TI  - Fixed Drug Eruption due to Fluconazole: Not so uncommon Now-a-days.

PMID- 25584247
TI  - Importance of denture marking for human identification in forensic odontology.

PMID- 25584248
TI  - Epidemiological Features of violence-related Injuries in Jamaica.
AB  - BACKGROUND: Violence-related injuries are common in Caribbean countries such as
      Jamaica and are a major cause of mortality and morbidity. The study examined the
      epidemiology of violence-related injuries and ascertained the extent to which the
      utilization of violence-related injury reports and surveillances inform health
      policy and programme planning implementation in Jamaica. MATERIALS AND METHODS:
      Primary data was gathered by the Ministry of Health through its Public Hospital
      Monthly Statistical Reporting System (HMSR) and the Jamaica Injury Surveillance
      System (JISS). These data files were collected over a four and five year period
      respectively. The sample size comprised 187,610 cases (117,615 from HMSR) and
      (69,995 from JISS) which were seen and treated at the public hospitals in Jamaica
      because of violence-related injuries. This study employed a descriptive analysis
      of visits and cases (episodes) relating to violence-relating injuries. Simple
      random sampling method was used in this study and the data was analysed using
      both Microsoft Excel and the Statistical Package for Social Scientists 18.0.
      RESULTS: The highest number of violence-related injuries was in 2007 and assault
      (stab wounds, gunshot and blunt injury) was the most frequent violence-related
      injury with human bites, and burns being the least. The highest number of
      violence-related injuries in males and females was in the age group 20-29 y. More
      males experienced violence-related injuries compared with females with male to
      female ratio of 1.35:1 to 1.45:1 in the years considered. CONCLUSION: The
      findings of this study are consonant with local and international studies and
      confirm that assault was the most frequent violence-related injury. Males
      compared with their female counterparts are a stronger demographic risk factor
      where violence-related injuries are concerned. Violence-related injuries have
      spurred the charge for effective interventions, policy initiatives, and strategic
      and programme planning by the Ministry of Health, through multi-sectoral and
      multi-agency approaches in Jamaica.

PMID- 25584249
TI  - Extensor Pollicis Longus Injury in Addition to De Quervain's with Text Messaging
      on Mobile Phones.
AB  - OBJECTIVE: To do a clinical and ultrasonic evaluation of subjects with thumb pain
      with text messaging. BACKGROUND: Thumbs are commonly used for text messaging,
      which are not as well designed for fine manipulative or dexterous work.
      Repetitive use as in text messaging can lead to the injury to the tendons of the
      thumb. MATERIALS AND METHODS: Ninety eight students with symptoms of Repetitive
      Strain Type of injuries of the thumb were selected from a survey and evaluated
      both clinically and by ultrasound analysis of the musculotendinous unit of the
      thumb to note changes due to excessive use of the mobile phone. Age and sex
      matched controls were also subjected to ultrasound evaluation. RESULTS: Clinical
      examination showed positive Finkelstein test in 40% of the cases, significant
      reduction in the lateral and tip pinch strengths in the cases. Ultrasound
      detected changes in the first and the third compartments in 19% of the cases.
      CONCLUSION: Isolated cases of pain in the thumb have been reported but this study
      noted changes both clinically and by ultrasound in the tendons of the thumb.
      These changes should be taken as warning signs of possible subclinical changes
      taking place in the soft tissues of the thumb in these subjects due to repetitive
      use of mobile phones and thus, making them prone for developing painful
      Musculoskeletal Disorders. APPLICATION: Repetitive use of mobile phones for text
      messaging can lead to the damage of Extensor pollicis longus of the thumb in
      addition to the tendons of the first compartment of the wrist.

PMID- 25584250
TI  - Evaluation of tibial condyle fractures treated with Ilizarov fixation, a
      prospective study.
AB  - BACKGROUND: Tibial plateau fractures are associated with significant soft tissue
      injuries which increases the risks of complications and must be considered when
      managing tibial plateau fractures. Various modalities of treatment are available
      for treatment of these fractures but Ilizarov fixation has a special advantage
      over others. Review of literature shows many studies of Ilizarov fixation in the
      treatment of tibial plateau fractures with variable results. Aim of our study was
      to evaluate tibial condyle fractures treated by Ilizarov fixation. MATERIALS AND
      METHODS: Study included 43 patients with Schatzker type II and above tibial
      plateau fractures treated by ilizarov fixation. Standard trauma evaluation, a
      meticulous musculoskeletal and neurologic examination was carried out. All
      patients underwent Ilizarov fixation by same team of surgeons. Clinicoradilogical
      assessment of the patients carried out at regular intervals. RESULTS: Our study
      included 43 cases of tibial plateau of various types except type I. Mean time for
      radiological union was 24.51 wk (range 15 to 32 wk). Mean fixator period was 26.6
      wk( 16-34 wk). The functional results were measured by Lyshom's and Hohl and Luck
      score. The mean Lyshom's score was at the end of one year was 82.16. At end of
      one year by Hohl and Luck grading 11 patients had fair, 23 had good and 9 had
      excellent results. CONCLUSION: High energy tibial plateau fractures can be
      definitively treated with Ilizarov external fixation. Treatment with this method
      gives good union rates and less risk of infection. Closed reduction, minimal soft
      tissue damage and early mobilization are the key to low complications.

PMID- 25584251
TI  - Comparative Study Using Intramedullary K-wire Fixation Over Titanium Elastic Nail
      in Paediatric Shaft Femur Fractures.
AB  - BACKGROUND: Fracture shaft femur is common paediatric trauma leading to
      significant morbidity. Conservative treatments available are associated with
      prolonged periods of immobilization. Use of flexible intramedullary implant
      allows early rehabilitation in diaphyseal fractures of femur in children. AIM:
      The aim of the present study is to compare fixation of diaphyseal femur fracture
      by titanium elastic nail and intramedullary K-wires in children. SETTING AND
      DESIGN: Prospective randomized study in a tertiary care hospital. MATERIAL AND
      METHODS: Fifty-two children between 6 years and 14 years of age with femoral
      shaft fracture were assigned either in Group I or Group II based on computer
      generated random numbers. In Group I closed percutaneous intramedullary K- wire
      fixation and in Group II closed percutaneous intramedullary titanium elastic nail
      was used to fix the fractures. Partial weight bearing was allowed after 6 weeks
      of surgery and full weight bearing at clinico-radiological union. RESULTS:
      Average time of radiological union was 6 to 10 weeks in both groups. In both the
      groups two cases had entry site irritation which resolved with early implant
      removal. One case in both the groups had unacceptable mal-alignment. Both the
      groups had few cases of limb-length discrepancy, which was in acceptable limit,
      except two cases of TENS. There was no statistically significant difference
      between the results of both the groups. But, using K-wires significantly reduced
      the cost of treatment. CONCLUSION: Most of such fractures in our society are
      neglected because of high cost of treatment. Providing a cheaper alternative in
      form of K-wires may be beneficial for the patients from low socio-economic
      status.

PMID- 25584252
TI  - Dual release paracetamol in osteoarthritis of knee: a randomized controlled
      clinical trial.
AB  - BACKGROUND: Paracetamol is recommended as first line agent for pain management in
      osteoarthritis (OA) by various guidelines. The main problem associated with
      management of osteoarthritis is long term patient compliance to paracetamol due
      to its frequent dosing. OBJECTIVE: To evaluate the efficacy and safety of
      Paracetamol 650 mg dual release tablet twice daily (PCM 650 dual release)
      compared to paracetamol 500mg immediate release tablet thrice daily (PCM 500 IR)
      in the treatment of Knee OA. MATERIALS AND METHODS: In this randomized, open
      label, parallel, active controlled clinical study, 250 patients of OA knee
      meeting inclusion criteria were randomized to receive either PCM 650 dual release
      two times daily or PCM 500 IR three times daily for 6 weeks. Patients were
      assessed at baseline, 2, 4 and 6 weeks. Primary efficacy measures were severity
      of pain (Visual Analogue Scale) and Knee injury and osteoarthritis outcome score
      (KOOS) subscale for pain at week 2, 4 and 6. Other KOOS subscales (symptoms other
      than pain, function in daily living, function in sport and recreation, quality of
      life) and patient's and physicians global assessment of therapy were included as
      secondary endpoints. RESULTS: Both treatment groups showed improvement in primary
      endpoints at each evaluation visit. Patients receiving PCM 650 dual release
      showed significant improvement of pain in both primary endpoints at each study
      visit compared to patients receiving PCM 500 IR (p<0.001). PCM 650 dual release
      was significantly superior to PCM 500 IR for improvement in all KOOS subscales at
      each study visit (p<0.01). Less number of patients required additional rescue
      analgesics in PCM 650 dual release group (16% patients vs 26%, PCM 500 IR;
      p>0.05). Adverse effects were significantly less in PCM 650 dual release group
      (6% vs. 14% in PCM 500 IR; p<0.05). Patient's and physician's global assessment
      of therapy favoured PCM 650 dual release than PCM 500 IR (p<0.001). CONCLUSION:
      Patients with symptomatic OA of the knee showed a greater improvement in pain and
      functional capacity with PCM 650 dual release than PCM 500 IR with better
      tolerability.

PMID- 25584253
TI  - A double-blind, rct testing beneficial modulation of BDNF in middle-aged, life
      style-stressed subjects: a clue to brain protection?
AB  - INTRODUCTION: The aim of this prospective study was to see whether LD-1227, a
      quality-controlled marine nutraceuticals shown to protect experimental stress
      induced hyppocampal degeneration, could beneficially modulate BDNF, as measured
      in the serum, in otherwise healthy but work-stressed individuals. MATERIALS AND
      METHODS: Forty-eight men and women between the ages of 38 and 62 reporting high
      demanding work activity but with an overall positive attitude towards their
      personal life were recruited. Subjects were divided in two group (24 patients
      each) and blindly supplemented for 2 month with: a) LD-1227 400mg or b) placebo.
      A third group of healthy non-stressed subjects was used as well. Blood samples
      were taken before and after the supplementation period. Unstimulated saliva was
      collected and tested for amylase while serum levels were used to measure BDNF.
      State Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI) and
      psychological well-being assessment (PSWB) were measured too. Patients with
      Val66Met functional polymorphism of BDNF excluded those given their reported
      association with an impaired release of BDNF. RESULTS: RESULTS showed that, as
      compared to healthy, non-stressed individuals, stressed ones has a trend decrease
      of BDNF and this was significantly increased by LD 12-1227 supplementation and
      the same inverse phenomenon occurred to salivary amylase (p<0.05). No change was
      noted in the PSQI score but, either STAI or PSWB tests scored better in LD-1227
      supplemented subjects. CONCLUSION: The present data suggest that LD-1227 is
      beneficially affecting neuromodulation and related symptoms during common
      stressful life conditions and may have the potential as tools in a
      neuroprotective clinical strategy.

PMID- 25584254
TI  - Hepatitis B & C among farmers - a seroprevalence study.
AB  - BACKGROUND: Hepatitis B & C are the two major causes of chronic liver disease,
      having the similar parenteral route of transmission, thereby responsible for
      significant morbidity and mortality. OBJECTIVE: Agriculture being the backbone of
      this part of country, the present study was undertaken to assess the
      seroprevalence of these diseases among the farmers which form the major
      occupation class in the Malwa belt of Punjab, India. MATERIALS AND METHODS:
      Screening camp was organized at Kisan Mela at the regional station of Punjab
      Agriculture University at Faridkot, Punjab. Blood samples were collected, and
      tested for HBsAg and anti-HCV. RESULTS: Total of 1219 subjects, 63% being in the
      age group of 30-50 years, were screened of which the seroprevalence of HCV & HBV
      was 5% and 0.32% respectively, and 72% of HCV positive cases were between 30-50
      years of age. CONCLUSION: The study stresses on the need of safe injection
      practices especially in villages and control on addiction, a more effective
      vaccination program for HBV, strict check on commercial blood banks, and
      community education regarding tattooing and sexual behaviour.

PMID- 25584255
TI  - Senior- loken syndrome - a ciliopathy.
AB  - Senior - Loken syndrome is a rare combination of juvenile nephronophthisis and
      tapeto - retinal degeneration. The author describes two patients who presented
      with varying degrees of retinal dystrophy and renal insufficiency in their second
      decade of life. Both the patients presented with severe renal failure requiring
      hemodialysis. The first patient had early onset progressive retinal degeneration
      leading to childhood blindness whereas the second patient had asymptomatic
      retinitis pigmentosa. These cases are presented to highlight the spectrum of eye
      manifestations of Senior - Loken syndrome. This report also stresses the need for
      fundus evaluation in patients with chronic kidney disease presenting in second
      decade of life even if asymptomatic. 

PMID- 25584256
TI  - Bronchoscopic removal of aspergilloma from a cavitary lesion of the lung.
AB  - We report a 62-year-old diabetic male who had recurrent episodes of haemoptysis,
      diagnosed to have Aspergilloma in the right upper lobe cavitary lesion of the
      lung. Bronchoscopic biopsy revealed a fungal ball (Aspergillus niger) in the
      right upper lobe. Since the patient did not respond to medical treatment, unfit
      for any surgical interventions, mechanical removal of the fungal ball was done
      with both rigid and flexible bronchoscopes. Patient improved symptomatically
      after the removal of the fungal ball; haemoptysis subsided. The patient is still
      under follow up without any further episodes of hemoptysis. This case report
      highlights a new alternative treatment option in patients with open cavitary
      Aspergilloma. 

PMID- 25584257
TI  - An unusual association of inflammatory pseudotumor of the liver and dorsal
      pancreatic agenesis presenting as reversible portal hypertension: a case report.
AB  - Inflammatory pseudotumor of liver although a rare entity is an important
      differential diagnosis of hepatic space occupying lesions as well as an important
      cause of portal hypertension, commonly mimicking malignant tumors on imaging and
      histology. We report a case of a 25-year-old postpartum female who presented to
      our emergency with seizures and altered sensorium and was found to be having
      uncontrolled hyperglycemia and metabolic encephalopathy. She had a 2 month
      history of low grade fever and pain in right hypochondrium. Examination revealed
      an enlarged, tender, left lobe of the liver, splenomegaly and ascites. CT scan of
      the abdomen revealed an ill-defined mass lesion in left lobe of the liver with
      dilated intrahepatic biliary radicles along with dorsal pancreatic agenesis and
      evidence of portal hypertension in the form of ascites and splenomegaly.
      Histopathology confirmed the presence of inflammatory pseudotumor in left lobe of
      the liver. Conservative management of the patient resulted in reduction of the
      tumor size and regression of splenomegaly and ascites in 1 month. Present case
      highlights inflammatory pseudotumor of liver as a rare entity, it's resemblance
      to malignant conditions, pancreatic agenesis as a previously unreported
      association as well as a potentially reversible cause of portal hypertension by
      conservative treatment only. 

PMID- 25584258
TI  - Carcinoid tumors of the appendix - last decade experience.
AB  - INTRODUCTION: Carcinoid of the appendix is a rare clinical entity in childhood
      and usually has a good clinical outcome. The impact of the operative preparations
      appendix ranges between 0.1-0.9%. The aim of our study is to report the
      experiences of our department in the management of appendiceal carcinoid tumors
      in children. MATERIALS AND METHODS: Data of all patients aged 15 y or less who
      underwent appendectomy at the 2nd Department of Pediatric Surgery of Aristotle
      University of Thessaloniki between January 2004 and February 2014 were evaluated
      for the existence of appendiceal carcinoid tumors in pathological specimens. The
      collected data included: gender, patient's age, clinical indications and surgical
      intervention, tumor localization in the appendix and the diameter of lesion,
      histological type of the tumor and postoperative care (follow up) of patients.
      RESULTS: Four cases (3 girls, 1 boy) with carcinoid treated at our department
      during a 10 y period. Median patient age was 10.75 y (9- 12 y). In all cases the
      diagnosis was after appendectomy on ground of acute appendicitis. A single
      incident brought findings of gangrenous appendicitis. In three cases the tumor's
      diameter was smaller than 1cm, while the incident with the gangrenous
      appendicitis was larger than 1cm in diameter. In four cases the tumor was
      localized at the apex of the appendix without extending to the surrounding
      tissues. In all patients with carcinoid tumor followed a further testing based on
      specific monitoring protocol. In no case was residual or metastatic disease
      identified and no further treatment was required. No relapse was observed during
      follow-up. CONCLUSION: Our study confirms the good prognosis of appendiceal
      carcinoid.

PMID- 25584259
TI  - A Comparative Study of RIPASA Score and ALVARADO Score in the Diagnosis of Acute
      Appendicitis.
AB  - BACKGROUND: Acute appendicitis is one of the most common surgical emergencies.
      Different techniques have been devised to assist in equivocal cases in attempts
      to decrease negative appendicectomy rates. A number of scoring systems have been
      used for aiding in early diagnosis of acute appendicitis and its prompt
      management of which Alvarado score is the most popular. The accuracy of Alvarado
      score in the diagnosis of acute appendicitis is disappointingly low in Asian
      population and RIPASA scoring has been designed for the diagnosis of acute
      appendicitis in the Asian population. So we prospectively applied and compared
      Alvarado and RIPASA score in the diagnosis of acute appendicitis in Indian
      population. MATERIALS AND METHODS: We compared prospectively RIPASA and Alvarado
      scoring system by applying them to 206 patients. Both scores were calculated for
      patients who presented with right iliac fossa pain during the study period.
      Depending on clinical judgment appendicectomy was done. Post operative
      histopathology report was correlated with the scores. A score of 7.5 is the
      optimal cut off threshold for RIPASA and 7 for Alvarado scoring system.
      Sensitivity, specificity, positive predictive value (PPV) and negative predictive
      (NPV) for RIPASA & Alvarado system was done. RESULTS: The sensitivity and
      specificity of RIPASA score were 96.2% and 90.5% respectively. The sensitivity
      and specificity of Alvarado score were 58.9% and 85.7% respectively. RIPASA score
      correctly classified 96 percent of all patients confirmed with histological acute
      appendicitis to the high probability group (RIPASA score greater than 7.5)
      compared with 58.9% with Alvarado score (Alvarado score greater than 7.0; p-value
      less than 0.001). CONCLUSION: RIPASA scoring system is more convenient, accurate,
      and specific scoring system for Indian population than Alvarado scoring system.

PMID- 25584260
TI  - Mesenteric fibromatosis (desmoid tumour) - a rare case report.
AB  - Mesenteric Fibromatosis (MF) is a proliferative fibroblastic lesion of small
      intestinal mesentery. It constitutes 8% of all desmoid tumours, which represent
      0.03% of all neoplasm. It is histologically benign but may invade locally and
      recur after excision. It occurs sporadically or in association with Familial
      adenomatous polyposis (FAP) mutation as a component of Gardner's syndrome. The
      presenting features of MF are asymptomatic abdominal mass, abdominal discomfort
      or pain, bowel or ureteral obstruction, intestinal perforation, fistula,
      functional impairment of ileoanal anastomosis following colectomy in FAP cases. A
      29-year-old male presented with a swelling on the right side of the umbilicus for
      six months and dull aching pain for two months. Fine needle aspiration cytology,
      ultrasonography, contrast enhanced computerized tomography findings were
      inconclusive. After Exploratory laparotomy, a mass approx 6x5x4 cm in ileal
      mesentery was identified and excised along with 20cm of ileum. End to end
      anastomosis was done and specimen was sent for histopathology which confirmed the
      diagnosis of MF. Considering the rarity of this tumour and difficulties in
      diagnostic and therapeutic ambit, we believe it is justified to describe this
      case which came to our observation. 

PMID- 25584261
TI  - Isolated common iliac artery aneurysm: a rare entity.
AB  - Isolated aneurysms in iliac artery are not common. A 65-year-old male patient
      presented with complaints of pain abdomen, abdominal distension and history of
      hypertension, Clinical examination revealed pulsatile mass in the right iliac
      fossa extending upto paraumbilical region with palpable pulsations in all the
      limbs. Computed tomographic (CT) angiogram was done and it revealed large
      aneurysm of right common iliac artery. CT chest and abdomen did not reveal
      aneurysm in thoracic and abdominal aorta. As the size of aneurysm was large and
      there was risk of rupture, surgical intervention in the form of aneurysmorrhaphy
      was done. Open surgery was done as the anatomy was not favourable for
      endovascular intervention. Aneurysmorrhapy was done using 6mm ringed Poly Tetra
      Fluoro Ethylene graft. Patient recovered well and was discharged after 10 days. 

PMID- 25584262
TI  - Chylolymphatic Cyst of Mesentery of Terminal Ileum: A Case Report in 8 Year-old
      Boy.
AB  - Mesenteric cysts are rare benign intra peritoneal tumor and more than half of the
      mesenteric cysts involve the mesentery of the terminal ileum. We present 8 year
      old boy, who presented with features of acute intestinal obstruction.
      Ultrasonography (USG) of the abdomen revealed a cystic mass in the peritoneal
      cavity with dilated loops of bowel. Exploration of the abdomen revealed a
      solitary cyst of the mesentery of the terminal ileum measured 10 x 8 cm. There
      was twisting of the part of the ileum (volvulus) due to the cyst. It also
      involved the wall and lumen of the adjacent ileum and there were dilated bowel
      loops proximal to the cyst. Complete cyst excision and resection of the part of
      the ileum involved with the cyst was done en bloc. An ileostomy was created due
      to gross disparity in the lumen of the ileum, which was closed two and half month
      later. Histopathology of the excised cyst was consistent with the chylolymphatic
      cyst (mesenteric cyst). 

PMID- 25584263
TI  - Primary renal large cell neuroendocrine carcinoma in a young man.
AB  - Neuroendocrine tumours are usually located in the gastrointestinal or respiratory
      tract. A 23-year-old man was evaluated for loss of weight and a palpable left
      loin mass. CECT showed a large heterogeneously enhancing mass with calcification
      arising from the left kidney. He underwent an open radical nephrectomy.
      Histopathological examination revealed a large cell neuroendocrine carcinoma
      (LCNEC). LCNEC of the kidney is extremely rare and portends poor prognosis. It is
      usually a histopathological surprise and requires immunohistochemistry for
      confirmation. 

PMID- 25584264
TI  - Phaeohyphomycotic cyst in the Foot by Exophiala.
AB  - A 52-year-old male, presented to us with a swelling over plantar aspect of right
      foot following trauma. Clinically it was a cystic swelling diagnosed as an
      abscess; ultrasound showed thick walled multilocular collection with thick
      echogenic debris, following which complete excision of the swelling was done. A
      part of the swelling was sent for histopathological examination and cut section
      showed thick purulent material. Other part sent for culture sensitivity grew,
      Exophiala, which belongs to Dematiaceous group of fungi. Surgical excision with
      antifungal treatment is the management in general for fungal cyst, whereas in our
      case complete excision was done without antifungal treatment. 

PMID- 25584265
TI  - Acute suppurative thyroiditis accompanied by thyrotoxicosis after fine-needle
      aspiration: treatment with catheter drainage.
AB  - Fine needle aspiration (FNA) biopsy is commonly used in the diagnosis of thyroid
      diseases. Serious complications are rare and this procedure is generally safe.
      Acute supurative thyroiditis (AST) after FNA has been seldomly reported. We
      report a case of a 57-year-old women with diabetes mellitus who developed AST
      with thyrotoxicosis after FNA. She was successfully treated by sonographically
      guided percutaneous drainage and antithyroid agent. 

PMID- 25584266
TI  - Anterior abdominal wall haemangioma with inguinal extension.
AB  - Haemangioma are common benign vascular tumour but Intramuscular haemangiomas are
      rare tumours comprising less than 1% of all. The most frequent sites are
      extremities, head and neck whereas abdominal wall is a quiet rare location.
      Ultrasonography is an appropriate initial diagnostic modality and MRI is the
      investigation of choice. A rare case presented to us as Intramuscular haemangioma
      of anterior abdominal wall with inguinal extension. Ultrasonography with Doppler
      study and MRI was suggestive of same finding. Intraoperatively patient had huge
      haemangioma involving external oblique, internal oblique and transverse abdominus
      muscle. Wide local excision with meshplasty was done as part of muscle had to be
      removed. Histology confirmed the diagnosis of Intramuscular Haemangioma. 

PMID- 25584267
TI  - A case of Chronic Bilateral Axillary Hidradenitis.

PMID- 25584268
TI  - Simultaneous primary hydatid cysts of liver and spleen with spontaneous
      intraperitoneal rupture of liver cyst.

PMID- 25584269
TI  - An unusual complication of esophageal stenting for corrosive Acid injury.

PMID- 25584270
TI  - Alpha-foetoprotein in the diagnosis of prelabour rupture of membranes.
AB  - CONTENT: Prelabour rupture of membranes (PROM) complicates overall 10% of
      gestations which include 7% at term and 3 % preterm gestations. Making an early
      and accurate diagnosis of PROM is important, to allow gestational age specific
      obstetric interventions and to optimize perinatal outcome. OBJECTIVE: To study
      the efficacy of alpha-foeto protein in cervicovaginal secretions, to diagnose
      prelabour rupture of membranes. SETTING: A tertiary care centre. MATERIALS AND
      METHODS: We performed a prospective study on 130 patients who were at >= 24 weeks
      of gestation, who had complaint of leaking per vagina, between September 2011 and
      August 2013. Alpha-foetoprotein test was perfomed on cervicovaginal secretions
      which were collected during per-speculum examinations. A diagnosis of prelabour
      rupture of membranes was made, based on combined clinical diagnosis which was
      made during hospital stay of the patients prospectively. The efficacy of Alpha
      foetoprotein was studied. Stastical Analysis: Chi-square test, Kappa analysis.
      RESULTS: The sensitivity, specificity, positive predictive value, negative
      predictive value and accuracy of Alpha-foetoprotein were 88.9%, 98.5%, 98.3%,
      90.1% and 93.8% respectively. Degree of agreement of Alpha-foetoprotein with
      combined clinical diagnosis was 0.875. CONCLUSION: Assessment of alpha
      foetoprotein levels in cervi-covaginal secretions can be used as a reliable test
      to diagnose prelabour rupture of membranes when faced with a diagnostic dilemma.

PMID- 25584271
TI  - Impact of fetal presentation on pregnancy outcome in preterm premature rupture of
      membranes.
AB  - AIM OF THE STUDY: To determine the impact of fetal presentation on pregnancy
      outcome in preterm premature rupture of membranes (PPROM). STUDY DESIGN:
      Retrospective. MATERIALS AND METHODS: Fifty eight PPROM patients (gestational age
      of 24-34 wk, complicated by PPROM and latency more than 24 h) between January
      2008 to December 2012 were categorized into cephalic and non cephalic and
      pregnancy outcome were analyzed with standard statistical methods including the
      Chi-square test, t- test and Mann Whitney test. RESULTS: The non cephalic (20.7%,
      12/58) and cephalic group (79.3%, 46/58) among the 58 patients with PPROM were
      demographically homogenous. PPROM was significantly earlier in non cephalic group
      although latency was not much different in both groups. Maternal complications
      (abruption, chorioamnionitis and post operative wound infection) as a composite
      were more in non cephalic group. Neonatal death was also significantly more in
      non cephalic than cephalic. CONCLUSION: Non cephalic presentation at diagnosis of
      PPROM is likely to have an unfavorable effect on the maternal and fetal outcome.

PMID- 25584272
TI  - Positive association of sperm dysfunction in the pathogenesis of recurrent
      pregnancy loss.
AB  - BACKGROUND: Recurrent pregnancy loss (RPL) is one of the most frustrating and
      difficult areas in reproductive medicine, because the aetiology is often unknown
      and there are few evidence-based diagnostic and treatment strategies. RPL
      diagnosis is mainly focused on the female partner. The male factor contributing
      in evaluation of RPL has been less investigated, it is restricted to karyotype
      and basic semen analysis, assessment of functionality of sperm is largely
      ignored. AIM AND OBJECTIVE: To investigate the role of sperm factors in RPL
      through regular semen analysis preceded with sperm function tests. MATERIALS AND
      METHODS: We performed a case control study of 95 males whose partner has
      experienced two or more pregnancy loss as case and 37 volunteers who had fathered
      child/children without the history of RPL as control group. Basic semen analysis
      and sperm function test (Nuclear chromatin decondensation {NCD}, Hypo osmotic
      swelling {HOS} and Acrosome intactness test {AIT} was performed. The results were
      analysed by performing Independent-sample t-test using SPSS (version 14.0).
      RESULTS: One individual had anatomical abnormality which was confirmed through
      trans-rectal ultrasound scanning and RPL group showed statistically significant
      (p<0.05) value for NCD, HOS and AIT and 36.8% of RPL individuals had reduced
      score for sperm count and motility. Less than 4% normal morphology was recorded
      in 16.8% individuals of RPL group. CONCLUSION: Our study revealed that the
      positive association of sperm dysfunction in RPL cases, hence male may be
      considered for a routine part of the evaluation along with his partner in the
      near future in order to achieve desirable outcome.

PMID- 25584274
TI  - Postmenopausal huge ovarian leiomyoma: a rare presentation.
AB  - Ovarian leiomyoma is one of the rare solid tumours of ovary, accounting for 0.5
      1% of the benign tumours of the ovary. We report one such case which presented in
      a postmenopausal woman. The differential diagnosis includes ovarian fibroma,
      thecoma, cellular fibroma and sclerosing stromal tumour. Masson's trichrome
      staining helps to distinguish fibrous and smooth muscle components of the lesion
      and confirms the diagnosis of ovarian leiomyoma. Hence, ovarian leiomyoma should
      be considered in the differential diagnosis of ovarian spindle cell tumours. 

PMID- 25584273
TI  - Herpes Gestationis after Ovodonation: Is Placenta the only Target of the Immune
      Reaction?
AB  - Herpes Gestationis (HG) is an autoimmune disorder that rarely complicates
      pregnancy. Its pathogenesis has not been clarified yet, as it derives from a
      complex interplay between immunologic, genetic, and hormonal factors. We present
      a case of HG occurring in a surrogate mother whose pregnancy was achieved via egg
      donation and in vitro fertilisation (IVF). The disease appeared at 26 weeks and 6
      days of gestation and subsequently worsened despite the administration of oral
      and topic corticosteroids. A healthy baby was delivered at 35 weeks and 2 days of
      gestation by elective cesarean section and the clinical manifestations resolved
      in the postpartum period. 

PMID- 25584275
TI  - Secondary vaginal atresia treated with vaginoplasty using amnion graft: a case
      report.
AB  - We report a case of 26-year-old primipara with last child birth 1.5 year back who
      presented with amenorrhoea, cyclical lower abdominal pain and dyspareunia for
      past six months. Examination revealed vaginal atresia secondary to previous
      traumatic/mismanaged vaginal delivery with haematocolpos. She was managed by
      vaginoplasty with amnion graft and regular dilation with soft vaginal mould for
      six weeks and was advised for regular intercourse after that. On follow up our
      patient was doing well with restoration of normal coital function. 

PMID- 25584276
TI  - Prevalence of Heptavalent Vaccine-related Pneumococcal Serotypes in
      Nasopharyngeal carrier in children under five years old in Shahrekord, Iran by
      Multiplex-PCR during 2010- 2011.
AB  - BACKGROUND: Heptavalent pneumococcal vaccine which included pneumococcal
      serotypes 4, 6B, 9V,14, 18C, 19F and 23F has been regularly used and is effective
      on preventing invasive pneumococcal infection. This study aimed to determine
      vaccine-related serotype distribution in nasopharyngeal carrier and healthy
      children under five years old. MATERIALS AND METHODS: In this cross-sectional
      study from September 2010 to September 2011, 363 nasopharyngeal specimens were
      collected from healthy children in day care centers. In positive cultures of
      streptococcus pneumoniae (S. pneumonia) distribution, serotypes were detected by
      Multiplex polymerase chain reaction (PCR). Electrophoresis of PCR products was
      used for detection of serotypes of S. pneumoniae. RESULTS: The carrier rate of S.
      pneumoniae was 29.5% with 95% confidence interval as 24.8- 34.5%. Electrophoresis
      of PCR products for detection of serotypes of S. pneumonia revealed 430, 220,
      753, 189, 573, 304, and 384 bp (s) for 4, 6B, 9V, 14, 18C, 19F, and 23F serotypes
      of S. pneumoniae, respectively. The frequency of 23F, 6B, 19F, and 18C serotypes
      were 43%, 34%, 18%, and 5% respectively, but other serotypes (4, 9V and 14) were
      not detected. CONCLUSION: Based on the 30% carrier rate and high prevalence of
      most of heptavalent pneumococcal conjugate vaccine serotypes in our study, this
      vaccine should be used for prevention of invasive infection in Iranian children.

PMID- 25584277
TI  - Waist Circumference, Waist-to-Height Ratio and Body Mass Index of Thai Children:
      Secular Changes and Updated Reference Standards.
AB  - BACKGROUND: The prevalence of obesity in pediatric age group has been increasing
      globally. Body mass index (BMI), waist circumference (WC) and waist-to-height
      ratio (WHtR) are commonly used to define obesity. The cut-off references for
      these parameters vary between racial and ethnic groups. We aimed to measure the
      secular changes and update the reference standards for these three parameters for
      Thai children in this study. MATERIALS AND METHODS: We completed a cross
      sectional survey of 3,885 school children 6.0-12.99 y of age in Ongkharak
      district of central Thailand during May to June 2013. Weight, height and WC were
      recorded by trained staff using sensitive and calibrated instruments. BMI and
      WHtR were calculated by standard formulae. The summary estimates were described
      by gender and whole year age groups. Age and gender specific smoothened
      percentile curves were created by using least mean squares method. The data was
      compared with that from a 2008 cohort from the same area. RESULTS: Age and gender
      specific percentile data and curves of WC, WHtR and BMI have been provided for
      Thai children. BMI and WC increased but WHtR changed relatively little with age
      in both genders. In comparison to 2008, WC and WHtR have increased consistently
      across all age groups and both genders. The 75th percentile for WHtR corresponded
      closely to 0.50 in both genders which has been the suggested cut-off. CONCLUSION:
      Since 2008, there have been significant increase in WC and WHtR across all age
      groups and in both genders in Thai children. These indicate increasing prevalence
      of central obesity and upcoming cardio-metabolic health problems. This needs to
      be tackled urgently by creating awareness and promotion of healthy diets and
      physical activities in school children. WC and WHtR should be routinely measured
      in paediatric examination for early diagnosis of central obesity.

PMID- 25584278
TI  - Neonatal Brain Abscess due to Extended-Spectrum Beta-Lactamase Producing
      Klebsiella pneumoniae.
AB  - Klebsiella pneumoniae (K. pneumoniae) causing brain abscess in newborn infants is
      rare. Presented herein, is a 27-day-old male neonate who developed two frontal
      lobe abscesses in association with K. pneumoniae sepsis and meningitis.
      Antibiotic susceptibility testing utilizing the double-disk synergy method
      (Cefotaxime and Amoxycillin-Clavulanate) confirmed the extended spectrum beta
      lactamase (ESBL) production by the isolate. He was treated simultaneously with
      antibiotics (Meropenem and Amikacin) and abscess aspiration through the anterior
      fontanelle, with less than satisfactory outcome. ESBL producing K. pneumoniae
      brain abscess in neonates is extremely rare in the English literature. Emperical
      carbapenems and aminoglycoside coverage in neonates with K. pneumoniae sepsis and
      brain abscess, especially in areas with high rate of ESBL producing bacteria may
      be warranted. 

PMID- 25584279
TI  - Infantile onset alexander disease with normal head circumference: a genetically
      proven case report.
AB  - Alexander disease (AD) is an autosomal dominant leukodystrophy which
      predominantly affects infants and children. The infantile form comprises the most
      common form of AD. It presents before two years of age and characterized by
      macrocephaly, psychomotor regression, spasticity, pyramidal sign, ataxia and
      seizures. The diagnosis is based on magnetic resonance imaging (MRI) findings and
      confirmed by Glial fibrillary acidic protein (GFAP) gene molecular testing. We
      report an Indian case with normal head circumference. 

PMID- 25584280
TI  - Lethal short limb dwarfism: thanatophoric dysplasia- type I.

PMID- 25584281
TI  - Diffuse hypopigmentation followed by hyperpigmentation in an african american
      woman with hemangiopericytoma treated with dasatinib.
AB  - Dasatinib is a second-generation multi-target tyrosine kinase inhibitor (TKI)
      that has activity against many imatinib-resistant BCR-ABL mutant forms, Src, and
      c-Kit tyrosine kinases. While skin hypopigmentation is a well recognized adverse
      effect of first generation TKIs; it has rarely been reported with dasatinib. We
      report a unique case of diffuse cutaneous hypopigmentation induced by dasatinib
      followed by hyperpigmentation occurring in the same patient. A 52-year-old
      African American female with a history of metastatic hemangiopericytoma was
      initiated on dasatinib as part of a clinical trial. After 2 months of treatment,
      she developed generalized skin hypopigmentation. Within 1 month of discontinuing
      the drug, the patient's skin pigmentation returned to normal. However, she then
      developed diffuse skin hyperpigmentation over the next couple of months. The
      hyperpigmentation was self-limited, and eventually resolved after several months.

PMID- 25584282
TI  - Predicting lumbar central canal stenosis - a magnetic resonance imaging study.
AB  - BACKGROUND: Low back pain is a common complaint among adults, worldwide. Lumbar
      canal stenosis is frequently diagnosed as a cause for low back pain. In this
      study we evaluate morphometric measures using MRI sections to predict the
      occurrence of lumbar central canal stenosis. SETTINGS AND DESIGN: One hundred and
      fifty four lumbar spinal MRI sagital and axial section images, 77 males and
      females each were evaluated from the Department of Radiology, Kasturba Medical
      College, Mangalore, Manipal University. The study design was a prospective study.
      MATERIALS AND METHODS: Various measurements were taken and two constant ratios
      were calculated. The Canal Body Ratio and the Ratio between the area of the dural
      sac and the vertebral body was evaluated. STATISTICAL ANALYSIS: Unpaired t-test
      analysis was conducted using SPSS software. RESULTS: A canal body ratio less than
      0.6 from L1 to L3 levels and less than 0.5 at L4 and L5 levels were found. The
      ratio between area of dural sac and vertebral body was found to be a constant at
      0.2 at all levels. It was found that maximum central canal stenosis occurred at
      the L5 lumbar vertebral level in 15.6% males and 13% females. This was followed
      by stenosis at the L4 and L3 lumbar vertebral levels with 5.1% males having
      stenosis at both levels and 3.9% and 5.1% females in L4 and L3 lumbar levels
      respectively. CONCLUSION: These morphometrical findings of the lumbar vertebrae
      could be of use in evaluating the possible cases of lumbar canal stenosis.

PMID- 25584283
TI  - Energy status and metabolism in intracranial space occupying lesions: a
      prospective 31p spectroscopic study.
AB  - AIM: Intracranial space occupying lesions can be infective or tumour. There are
      various advanced Magnetic resonance imaging techniques like perfusion, diffusion
      and proton spectroscopy which can differentiate between them. However, (31)
      Phosphorus spectroscopy studies the energy status and the metabolism pattern of
      various tissues and can be used potentially to differentiate between them
      depending on their Metabolism pattern. Thus, we aimed to study energy status of
      various intracranial lesions and try to differentiate between them including
      grades of gliomas. MATERIALS AND METHODS: (31)PMRS was done in 1.5T MRI in 43
      patients prior to surgery or through/via stereo-tactic biopsy, of which 25 were
      men and 18 women with mean age 41.34 y ranging from 7-71 y. Single voxel
      phosphorus spectroscopy was done from the solid portion of the lesions and data
      was analysed and post processed. RESULTS: Study includes Lymphoma (n=6), Grade 1
      and 2 glioma (n=5), grade 3 glioma (n=9), grade 4 glioma(n=6), metastases (n=5),
      tuberculoma (n=7) and pyogenic abscesses (n=5). The integral values of PME, Pi,
      PDE, gamma-ATP, alpha-ATP, beta-ATP with reference to the position of PCr were
      calculated along with various ratios. Integral values of Pi and PDE were
      significantly increased in metastases but decreased in gliomas grade 1-2 compared
      to other pathologic conditions. Mean integral values of LEP (low energy
      phosphates) and total phosphates were significantly decreased in gliomas grades 1
      and 2 and increased in metastases when compared with other pathologic conditions.
      PCr /Pi was increased in glioma grades 1, 2 and 3 but decreased in metastases;
      the significance was observed only in gliomas grade 3 and metastases. Metabolic
      ratios of PDE/beta ATP and Pi/betaATP were decreased in glioma grades 1 and 2 and
      increased in metastases with statistical significance. CONCLUSION: (31)PMRS may
      help in differentiating primary from secondary lesions and assess grades of
      gliomas.

PMID- 25584284
TI  - Evaluation of bowel wall thickening by computed tomography to differentiate
      benign from malignant lesions.
AB  - PURPOSE: Computed tomography(CT) is an excellent non-invasive modality to
      evaluate bowel wall thickening.The aim of our study was to evaluate CT appearance
      of bowel wall thickening due to various benign and malignant conditions taking
      into consideration pattern of attenuation, bowel wall thickness, extent of
      lesion, symmetry of lesion and other associated CT findings. MATERIALS AND
      METHODS: The prospective study was carried out on 50 patients who underwent
      computed tomographic evaluation of abdomen for suspicion of bowel pathology based
      on ultrasonography, barium studies and/or clinical grounds. The studies were
      conducted on Siemens ART and GE High speed CT scanners. The examination was
      performed as is done routinely for an abdominal scan with imaging done from
      diaphragm to pubic symphysis in supine position with the right lateral decubitus
      scans in selected cases for better characterization of gastric antral and
      duodenal lesions. Oral, rectal and intravenous (IV) contrast agents were
      administered. The diagnosis was confirmed by cytology or histopathology of any
      biopsy or surgical specimen. However, in cases where surgery was not done,
      diagnosis was confirmed by clinical response to medical treatment. RESULTS: Based
      on the various CT characteristics of abnormal bowel wall thickening, sensitivity
      and specificity of classifying a lesion as benign or malignant were calculated.
      Majority of the malignant bowel lesions were showing the following
      characteristics i.e. heterogeneous pattern of enhancement, marked bowel wall
      thickening, asymmetry of the lesion and focal/segmental bowel involvement.
      Overall, CT showed a sensitivity of 97% and specificity of 93% in differentiating
      between benign and malignant etiology of abnormal bowel wall thickening.
      CONCLUSION: Due to its high sensitivity and specificity, CT is an ideal imaging
      modality for differentiating between benign and malignant etiology of abnormal
      bowel wall thickening. Radiologists should be aware of the usefulness of specific
      CT criteria of bowel wall thickening to better differentiate benign lesions from
      malignant or potentially malignant lesions that warrant further diagnostic
      evaluation.

PMID- 25584285
TI  - Correlation of qualitative and quantitative MRI parameters with neurological
      status: a prospective study on patients with spinal trauma.
AB  - INTRODUCTION: Spinal trauma is relatively more common in young active
      individuals. Although its mortality is low, it is an important cause of long term
      disability. Magnetic resonance imaging (MRI) can accurately depict presence and
      extent of spinal cord injury (SCI) in these patients. This study was aimed to
      look for various qualitative and quantitative MRI findings which are predictive
      of initial neurological deficit in patients with spinal trauma and final outcome
      on follow-up. MATERIALS AND METHODS: The present study was conducted on 50
      patients with suspected acute cervical or dorsal spinal trauma presenting for MRI
      study. American Spinal Injury Association (ASIA) motor score was used for
      assessing neurological status at the time of presentation, at the time of
      discharge/2weeks and at 3-6 months follow up. Various MRI qualitative and
      quantitative parameters were evaluated for correlation with severity of spinal
      injury. RESULTS: Normal baseline MRI (pattern 0) was seen in 12 subjects and was
      associated with incomplete SCI in 4 subjects (ASIA grade D) followed by complete
      recovery in all patients on follow-up examination. Pattern I (haemorrhage) was
      associated with complete spinal cord injury. Pattern II (oedema) was associated
      with incomplete SCI and good functional recovery on follow up.Pattern III
      (contusion) was associated with intermediate severity of injury. Compression and
      transection patterns were associated with complete neurological deficit at
      presentation and increased mortality at subsequent follow-up. All the three
      quantitative parameters i.e. lesion length,maximum (bony) canal compromise (MCC),
      maximum spinal cord compression (MSCC) were significantly increased in patients
      with complete SCI as compared to those with incomplete SCI. The best predictors
      for baseline ASIA score were MCC, cord oedema and cord haemorrhage. For the final
      ASIA score, the best predictors were baseline ASIA score and cord haemorrhage.
      CONCLUSION: MRI is excellent imaging modality for detecting and assessing
      severity of spinal trauma. In our study, presence of cord haemorrhage, MCC and
      cord oedema were best predictors of baseline neurological status at presentation,
      whereas baseline ASIA score and cord haemorrhage were best predictors of final
      neurological outcome.

PMID- 25584286
TI  - Malignant Colojejunal Fistula First Discovered on CT: A Case Report.
AB  - Benign coloenteric fistula is an uncommon condition. It may occur secondary to
      diverticular disease, peptic ulcer, inflammatory bowel disease and so on.
      Malignant coloenteric fistula is a rare occurrence. Here we present a rare case
      of malignant colojejunal fistula secondary to locally invading colonic
      malignancy. 

PMID- 25584287
TI  - Imaging Diagnosis of Urethral Leiomyoma, usual Tumour at an Unusual Location.
AB  - Leiomyomas are benign tumours of smooth muscle origin and are the most common
      uterine masses in females of reproductive age group. Extrauterine leiomyomas are
      also encountered occassionally and most commonly they involve the genitourinary
      tract. Leiomyomas arising from urethral smooth muscle are exceptionally unusual
      which can pose a diagnostic dilemma. Patients usually present with urinary
      complaints and an intraluminal soft tissue mass bulging from urethral meatus. We
      are presenting the imaging findings of leiomyoma of distal urethra presenting as
      a perineal mass with histopathological correlation. 

PMID- 25584288
TI  - Congenital porencephaly in a new born child.
AB  - A 2-day-old male child presented with history of enlarged head and seizures since
      birth, born by caesarean section. Head circumference was 56 cm (dilated) with
      widely open anterior and posterior fontanelle. Routine investigations were within
      normal limits. CT head revealed a large non-enhancing fluid attenuating cystic
      lesion in posterior parietal and occipital region with communicating to dilated
      bilateral lateral ventricles and subarachnoid space. 

PMID- 25584289
TI  - Images in Medicine: Giant Cell Tumour of the Talus in a 7-Year-old Boy.

PMID- 25584290
TI  - Ivacaftor: a novel mutation modulating drug.
AB  - Cystic fibrosis (CF) is multisystemic disorder presenting in newborn period to
      adulthood, predominantly affecting respiratory system. It is caused by mutation
      in CF transmembrane conductance regulator gene. DeltaF508 is the most common
      mutation seen worldwide. Supportive management with bronchodilators, anti
      inflammatory, mucolytics, antibiotics are the corner stone of therapy. Mutation
      specific drug, Ivacaftor, was recently approved USFDA in January 2012 for
      patients carrying G551D mutation. It is approved in patients who are six years
      and older in 150 mg twice daily dosing schedule with fat containing meals. It
      improves the lung function and other aspects of disease including weight gain.
      The side effects like upper respiratory infection, headache, rash, diarrhoea,
      stomach ache and dizziness are mild and self-limiting. This is excellent example
      of promise of personalised medicine - targeted drug that treat patients with
      specific genetic makeup. 

PMID- 25584291
TI  - A Comparative Study of Clear Corneal Phacoemulsification with Rigid IOL Versus
      SICS; the Preferred Surgical Technique in Low Socio-economic group Patients of
      Rural Areas.
AB  - CONTEXT: Low socio-economic group patients from rural areas often opt for free
      cataract surgeries offered by charitable organisations. SICS continues to be a
      time tested technique for cataract removal in such patients. In recent times,
      camp patients are sometimes treated by clear corneal phacoemulsification with
      implantation of a rigid IOL, which being more cost effective is often provided
      for camp patients. This study was undertaken to find out which surgical technique
      yielded better outcomes and was more suited for high volume camp surgery. AIM: To
      find the better surgical option- phacoemulsification with rigid IOL or SICS, in
      poor patients from rural areas. SETTINGS AND DESIGN: A prospective randomised
      controlled trial of cataract patients operated by two different techniques.
      MATERIALS AND METHODS: One hundred and twelve eyes were selected and were
      randomly allocated into two groups of 56 eyes each. At completion of the study,
      data was analysed for 52 eyes operated by clear corneal phacoemulsification and
      implantation of a rigid IOL, and 56 eyes operated by SICS. STATISTICAL ANALYSIS
      USED: Unpaired t-test was used to calculate the p- value. RESULTS: The results
      were evaluated on the following criteria. The mean post-operative astigmatism at
      the end of four weeks - was significantly higher in phacoemulsification group as
      compared to SICS group The BCVA (best corrected visual acuity) at the end of four
      weeks - was comparable in both groups. Subjective complaints and/ or
      complications: In phaco group two patients required sutures and seven had striate
      keratitis , while none in SICS group. Complaint of irritation was similar in both
      groups. Surgical time- was less for SICS group as compared to phaco group.
      CONCLUSION: SICS by virtue of being a faster surgery with more secure wound and
      significantly less astigmatism is a better option in camp patients from rural
      areas as compared to phacoemulsification with rigid IOL.

PMID- 25584292
TI  - Intellectual disability and multiple co morbid psychiatric disorders in a child:
      a case report.
AB  - Comorbid psychiatric Disorders are seen commonly in people with intellectual
      disability and in fact they are at greater risk for developing other health
      disorders. Most prevalent chronic health conditions in children with intellectual
      disability are epilepsy, cerebral palsy,anxiety disorders, sleep disorders and
      autism spectrum disorders. Co morbidities multiply the problem of people with
      intellectual impairment to a great extent and hence an accurate psychological
      assessment of multiple diagnoses is useful in detecting the specific underlying
      processes differentiating the co morbid syndrome and in planning an appropriate
      management and rehabilitation program. This case report is presented to emphasize
      the fact that though. It is common for intellectually disabled children to have
      other co-morbid psychiatric disorders, it is important to have accurate, suitable
      assessment and recording of every co-morbid disorder as it has its own
      implication in course and outcome of the disability in the child. A comprehensive
      management approach involving people from various spheres would be required to
      improve the quality of life and for reduction of burden of care giver.We describe
      a child of intellectual disability with multiple co morbidities. 

PMID- 25584293
TI  - Effective Factors on Patients' Satisfaction with Emergency Care Services using
      Factor Analysis: A Cross Sectional Study.
AB  - INTRODUCTION: Due to certain physical and psychological conditions of patients in
      emergency wards, pay attention to the effective factors on Patients' satisfaction
      is an essential issue in modern medicine. The aim of the present study was to
      investigate the effective factors on Patients' satisfaction with emergency
      medical services. MATERIALS AND METHODS: A cross-sectional survey was carried out
      from November to December 2010. The study sample consisted of 100 patients
      hospitalized in the emergency wards of Imam and Mustafa Hospitals in Ilam- Iran.
      Subjects were selected through simple random sampling method. Data gathered using
      questioner. The questioner validity was obtained using the content validity.
      Reliability of questionnaire was checked using Cronbach alpha coefficient. To
      find the most important factors affecting patient satisfaction, factorial
      analysis technique was used. RESULT: Exploratory factor analysis showed that the
      Patients' satisfaction is composed of six factors, including: satisfaction of
      physicians, nursing staff, the presence of students, the method of reception and
      discharge, deciding to cure and knowing the position of the therapist. Base on
      the results of the factorial analysis, the most important aspect of satisfaction
      was the satisfaction of physicians. The results revealed significant
      relationships between the occurrence time and the satisfaction of physician (r =
      0.23, p=0.027), the number of visits and the satisfaction of physician (r =0.27,
      p=0.01), the time of visits and the satisfaction of physician (p= 0.016), also
      between occurrence time and the number of visit (r = 0.36, p=0.001). CONCLUSION:
      Physicians and nurses actions and decision making are the major affecting factors
      satisfaction in emergency patients. Thus improving the quality of these factors
      will improve the quality of emergency services for patients.

PMID- 25584294
TI  - Emerging ethical perspective in physician-patient relationship.
AB  - Traditional health systems, with patients as passive recipients of care, have
      proven unsuccessful in stemming the most irresistible and exponential growth of
      the epidemic we now face. There is considerable healing power in a good Physician
      patient relationship. In the field of healthcare, patient empowerment has been
      acknowledged as an alternative to compliance in order to guide the provider
      patient relationship. It will help patients' confusion, fear and doubt slowly
      transform into clarity, relief and assurance. With the positive role of
      physicians, patients will definitely be relieved of hopelessness, have higher
      satisfaction, better adherence and improved health. There is no doubt that this
      small gesture by physicians will be a precious gift to humanity. 

PMID- 25584295
TI  - Maxillary posterior teeth removal without palatal injection -truth or myth: a
      dilemma for oral surgeons.
AB  - BACKGROUND: Pain control is one of the most important factors for successful
      treatment. Each new measure to control pain has been looked as miraculous act at
      the initial stages. The improvements in agents and techniques for local
      anaesthesia are probably the most important advances in dental science to have
      occurred in the past years. AIM: To evaluate 4% articaine hydrochloride against
      2% lignocaine hydrochloride anaesthesia in providing adequate palatal anaesthesia
      in maxillary posterior regions, without the need for a palatal block. SETTINGS
      AND DESIGN: Healthy patients above 15 y of age and requiring bilateral extraction
      of their maxillary posterior teeth were included in this crossover study. The
      exclusion criteria included medical history of cardiovascular and kidney
      diseases, gastrointestinal bleeding or ulceration, allergic reactions to local
      anaesthetic, pregnancy or current lactation. MATERIALS AND METHODS: Eighty
      patients, requiring bilateral extraction of their teeth due to various reasons
      were enrolled for this study. Each patient received both lignocaine and articaine
      anaesthetic in equivalent dose at two different appointments. Maxillary
      infiltration technique was used for extraction of maxillary posterior teeth at
      both the appointments. A 170-mm Heft Parker visual analogue scale was used to
      assess the pain on the palatal mucosa after buccal infiltration of either
      anaesthetic agent. Blood pressure, Pulse rate and electrocardiographic monitoring
      were done during the procedure. Adverse effects during the study period were also
      monitored. STATISTICAL ANALYSIS: Data was analysed by Z-test and student's t
      test. RESULTS: Pain scores on probing palatal mucosa after buccal infiltration of
      the anaesthetic were more for lignocaine as compare to articaine and it was
      statistically significant (p <.001). However, for hemodynamic parameters and
      electrocardiographic monitoring, there was no statistically significant
      difference in blood pressure, pulse rate and electrocardiograph before and after
      the completion of extraction (p > 0.05). CONCLUSION: Four percent articaine
      offers better clinical performance than 2% Lignocaine, particularly in terms of
      providing adequate palatal anaesthesia with only buccal infiltration.

PMID- 25584296
TI  - A Comparitive Evaluation of Sealing Ability, pH and Rheological Properties of
      Zinc Oxide Eugenol Sealer Combined with Different Antibiotics: An In Vitro Study.
AB  - AIM: The objective of this study was to evaluate and compare the sealing ability,
      pH & viscosity of Zinc oxide eugenol sealer mixed with different antibiotics
      (Amoxicillin, Ciprofloxacin, Clindamycin and Doxycycline). MATERIALS AND METHODS:
      Ninety single rooted anterior teeth were randomly divided into four experimental
      groups of 15 teeth each and 3 control groups of 10 each. Sealer-antibiotic
      combination was used as a sealer in experimental group. Teeth were sectioned
      longitudinally to assess linear dye penetration. pH and viscosity of the
      experimental groups were evaluated with Elico pH Meter and Brook Field Viscometer
      respectively. RESULTS: (Amoxicillin+ ZOE) Group II and (Clindamycin + ZOE) Group
      IV have shown minimum linear dye leakage of 1.07mm & 1.22 mm respectively &
      (Ciprofloxacin + ZOE) Group III and (Doxycycline + ZOE) Group V 2.69 mm & 2.59 mm
      respectively. There was decrease in the viscosity of the experimental group. pH
      was found to be 8.55 for Group II sealer which was greater than control group.
      CONCLUSION: Amoxicillin and sealer combination can improve the success rate of
      endodontic therapy by enhancing the antimicrobial activity, alkaline environment
      and reducing apical microleakage.

PMID- 25584297
TI  - Domestic violence and its effect on oral health behaviour and oral health status.
AB  - INTRODUCTION: Violence against women is one of the major public health and human
      rights problem in the world today. Hence, the present study was conducted with
      the aim to assess the effect of domestic violence on oral health behavior and
      oral health status of females attending community outreach programmes in and
      around Modinagar. MATERIALS AND METHODS: A cross-sectional study was conducted
      through the community outreach programmes organized in Modinagar. A structured
      questionnaire was used to illicit information regarding socio demographic
      characteristics, oral health behavior and domestic violence. The dental health
      examination was done to record dental health status, intraoral and extraoral soft
      tissue injury, tooth fracture and tooth avulsion due to the injury. RESULTS: Out
      of the total 304 women, 204(67.1%) reported positive domestic violence.
      Psychological violence was found to be severe whereas sexual violence was found
      to be mild in most of the cases. Significant difference was found between oral
      hygiene aids used , frequency of tooth brushing, periodontal status, missing
      teeth, intraoral soft tissue injuries and fractures between both the groups
      (p<0.05). CONCLUSION: The present study confirmed that domestic violence had
      significant influence on oral health behavior and oral health status of women.
      Thus, the dental professionals also should make an attempt to help victims gain
      access to support and referral services and to provide adequate treatment to them
      so as to make a positive difference in their lives.

PMID- 25584298
TI  - Characteristics of medial depression of the mandibular ramus in patients with
      orthodontic treatment needs: a panoramic radiography study.
AB  - BACKGROUND: Medial sigmoid depression or medial depression of the mandibular
      ramus (MDMR) is a known variant of the normal radiographic anatomy. The clinical
      importance of MDMR has been recognized, however, its prevalence and association
      with patients with orthodontic needs have been poorly documented. AIMS AND
      OBJECTIVES: To estimate the prevalence and characteristics of MDMR on panoramic
      radiographs of patients with different Angle's molar relation. MATERIALS AND
      METHODS: Three hundred panoramic radiographs of 100 each belonging to patients
      with Angle's class I, II and III molar relationship was recruited from an
      orthodontic clinic. The radiographs were evaluated for presence of MDMR along
      with its characteristics such as site and shape. The data was entered in the
      proforma and subjected for statistical analysis. RESULTS: The overall prevalence
      of MDMR in the present study was 23.2%. MDMR was found to be more prevalent in
      Class II - 28 (9.3%) followed by class III-23 (7.6%) and Class I- 19 (6.3%).
      There was equal distribution of MDMR with respect to site and the semilunar shape
      was the most common 36 (34%). All these findings were statistically non
      significant. CONCLUSION: Although MDMR is considered as a normal radiographic
      finding, the present study confirms the disparity in the prevalence of MDMR in
      patients with dentoskeletal deformities. Thus our findings suggest the importance
      of recognizing this entity prior to orthognathic surgery so as to avoid untoward
      sequelas.

PMID- 25584299
TI  - A comparative evaluation of gutta percha removal and extrusion of apical debris
      by rotary and hand files.
AB  - AIM: The aim of this study was to evaluate the efficacy of Protaper retreatment
      files in comparison with RaCe, K3 and H-files for removal of gutta-percha and
      apically extruded debris using volumetric analysis. MATERIALS AND METHODS: Forty
      extracted single rooted maxillary incisor teeth with straight canals and mature
      apices were selected for the study. After access cavity preparation, apical
      patency was confirmed with a size 10 K-file extending 1mm beyond the point at
      which it was first visible at the apical end. Working lengths were determined
      with the use of size 15 K-file. The canals were prepared in a step-back technique
      and the master apical file was size 30 for all teeth. 3% sodium hypochlorite was
      used as an irrigant after each instrumentation. Before final rinse, size 20 K
      file was passed 1mm beyond the apex to remove any dentinal shaving plugs and
      maintain the apical patency. Then the canals were dried with paper points. The
      root canal was filled using standard gutta-percha points and zinc oxide eugenol
      sealer under lateral condensation technique. The teeth were then randomly divided
      into four groups of ten teeth each based on the instrument used for gutta percha
      removal. All the rotary instruments used in this study were rotated at 300rpm.
      The instruments used were: Group 1 - RaCe Files, Group 2 - ProTaper retreatment
      Files, Group 3 - K3 Files and Group 4 - H Files. The volume of the obturating
      material was calculated before and after removal using volumetric analysis with
      spiral CT. The removal efficacy with each instrument was calculated and
      statistically analysed. RESULTS: The results of the study show that the ProTaper
      retreatment files (Group 2) (97.4%) showed the highest efficiency in the removal
      of obturating material, which was followed by RaCe (95.74%), K3 (92.86%) and H
      files (90.14%) with the efficiency in the decreasing order. Similarly the mean
      apical extrusion in H files (0.000 +/- 0.002) was significantly lower than all
      the rotary instruments. However, the difference among the rotary files were not
      statistically significant (p>0.05). CONCLUSION: ProTaper retreatment files show
      significant difference over other groups in removal of obturating material and
      can be the system of choice in endodontic retreatment procedures.

PMID- 25584300
TI  - Expression of inducible nitric oxide synthase in keratocystic odontogenic tumour
      and variants of ameloblastoma - a comparative study.
AB  - INTRODUCTION: The odontogenic keratocyst (OKC) is a histopathologiocally and
      behaviourally unique and specific entity. It is the most aggressive and recurrent
      of all the cysts and shows characteristics resembling both cyst and a tumour. The
      unique nature of OKC and the recent shift of OKC as a tumour made us evaluate yet
      another factor, Inducible nitric oxide synthase an (iNos) enzyme which has been
      implicated in the tumourigenesis of various neoplasms. Aims and Objects: The
      objective of the study was to analyse and compare the immunohistochemical
      expression of iNOS in odontogenic keratocysts (OKC's) in variants of
      ameloblastoma affecting the oral cavity, to determine the neoplastic potential of
      OKC and to reinforce the classification of OKC as keratocystic odontogenic
      tumour. MATERIALS AND METHODS: Thirty two specimens, eight specimens each in OKC,
      follicular ameloblastoma, plexiform ameloblastoma and unicystic ameloblastoma,
      taken from the Oral Pathology Department were randomly selected for this study
      and were evaluated for epithelial expression of iNOS by immunohistochemistry
      Results: Epithelial immunoreactivity to iNOS was strongly positive in 93.5% of
      follicular ameloblastomas, 68.7% of plexiform ameloblastomas, 66.9% of
      odontogenic keratocysts and 66.2% of unicystic ameloblastomas. CONCLUSION: iNOS
      may be an important marker involved in the biological behaviour of OKC.
      Furthermore the presence of increased expression of iNOS in Follicular
      ameloblastomas followed by Plexiform ameloblastomas, OKCs and Unicystic
      ameloblastomas is yet another evidence to support that OKC could be considered as
      a neoplasm.

PMID- 25584301
TI  - Efficacy of rebamipide and levamisole in the treatment of patients with recurrent
      aphthous ulcer - a comparative study.
AB  - Context (Background): Recurrent aphthous stomatitis is an inflammatory condition
      of unknown aetiology characterized by painful recurrent, single or multiple
      ulcerations of the oral mucosa. AIMS: To compare the efficacy of rebamipide, a
      gastro-protective agent and levamisole, an immunomodulating agent in the
      treatment of recurrent aphthous stomatitis. MATERIALS AND METHODS: Hundred
      patients diagnosed with recurrent aphthous stomatitis were enrolled in the study.
      Fifty patients were assigned randomly to each of the two treatment groups. After
      the clinical diagnosis and ulcer measurement, a subjective evaluation of symptoms
      was done for each subject. Both the drugs were given orally at specified
      intervals. Ulcer measurements and subjective evaluations were made at day one.
      STATISTICAL ANALYSIS: Analysis was done using various test like Mann Whitney and
      t-test. RESULTS AND CONCLUSION: The overall results showed mean number of
      episodes whose values were not statistically significant (p=0.43), neither were
      the mean number of ulcers (p=0.75), or values for mean size of ulcers (p=0.91).
      However, the overall results suggested that efficacy of rebamipide is almost same
      as that of the efficacy of previously proved drug levamisole. The current study
      with a three months follow up, including patients with high scores of pain,
      aphthae count, ulcer size and frequency of occurrence showed better results in
      both the study groups. However, rebamipide is suggested to be well tolerated and
      may therefore be useful in the treatment and prevention of frequently recurrent
      aphthous ulcers not restricted to Behcet's disease.

PMID- 25584302
TI  - Comparative study of fracture resistance of porcelain in metal ceramic
      restorations by using different metal coping designs- an in vitro study.
AB  - AIM: The aim of this study was to compare effect of different metal coping
      designs on fracture resistance of porcelain in metal ceramic restorations.
      MATERIALS AND METHODS: Fracture resistance of porcelain was assessed in porcelain
      fused to metal crowns with three different coping designs i.e. metal coping
      extension on labial surface upto gingivoaxial line angle, metal coping extension
      1mm short of the gingivoaxial line angle and metal coping with 0.4mm wide labial
      metal collar. For crowns without labial metal collar margin; shoulder porcelain
      was used to build the labial cervical margin of the crowns. RESULTS: RESULTS were
      assessed with statistical analysis using the student unpaired't' test. Visual
      examination of the fractured specimens of group A, B and C showed remarkably
      similar failure modes with nearly all specimens failing through a shear fracture
      of porcelain from load point to facial margin of the crown. CONCLUSION: Within
      the scope of this study, it was observed that the mean facture strength of the
      samples with shoulder porcelain labial margins having metal coping design
      extending upto gingivoaxial line angle of the finish line was highest as compared
      to samples with shoulder porcelain labial margins having metal coping design 1mm
      short of gingivoaxial line angle & samples having porcelain fused to metal coping
      design with 0.4mm wide metal collar.

PMID- 25584303
TI  - Effects of Green Tea on Streptococcus mutans Counts- A Randomised Control Trail.
AB  - CONTEXT: Mouth rinses have been in use from time immemorial as a supplement for
      routine oral hygiene. There are many number of mouth rinses currently available
      in the market in which many of them possess certain drawback, which has
      necessitated the search for alternate mouth rinses. AIM: The aim of the present
      study was to assess the effect of rinsing with green tea in comparison with
      chlorhexidine and plain water on Streptococcus mutans count. SETTING AND DESIGN:
      A short term, single blinded, cross over randomised control clinical trial.
      MATERIALS AND METHODS: Study includes a total of 30 subjects aged 20 to 25 years
      divided into three groups that is green tea group, chlorhexidine group, and plain
      water group. A baseline plaque samples were collected and under supervision of
      examiner all the subjects rinsed with 10 ml of respective solutions for one
      minute. Plaque samples were collected at five minutes after rinsing. All the 30
      subjects were exposed to all the three rinses with a wash out period of seven
      days between the interventions. All the samples were sent to microbial analysis.
      RESULTS: Wilcoxon matched pair test and Mann-Whitney U test showed that both
      chlorhexidine and green tea significantly reduced Streptococcus mutans colony
      counts compared to plain water. CONCLUSION: The results of present study indicate
      that green tea mouth rinse proved to be equally effective compared to
      chlorhexidine which is considered as gold standard. This may also be a valuable
      public health intervention as it is economical and has multiple health benefits.

PMID- 25584304
TI  - Modifications in Canal Anatomy of Curved Canals of Mandibular First Molars by two
      Glide Path Instruments using CBCT.
AB  - BACKGROUND: The creation of glide path reduces the risk of instrument breakage.
      Glide path is created before using NiTi rotary instrumentation Aim: This study
      compared the changes in the root canal anatomy after creation of glide path using
      Path Files (PF) and V Glide Path 2 (VGP2) using Cone Beam Computed Tomography
      (CBCT). MATERIALS AND METHODS: Hundred extracted mandibular first molars with
      curved mesial roots, curvature angles ranging within 20-30 degrees were assigned
      into two groups (n = 50 each). Glide path was prepared using PF (Group I) and
      VGP2 (Group II). CBCT images were obtained before and after instrumentation. The
      technical outcomes were compared at 0, 1, 2, 3, 5 and 7mm intervals. The data was
      analyzed using t-test and Chi-square test. RESULT: There was a statistical
      difference between the root canal curvatures and working time between the two
      groups (p < 0.05). Canals transported towards the distal side in Group II but
      there was a slight mesial transportation in Group I at 0mm. Group I exhibited a
      better centric ability except at 1mm interval (p > 0.05). The changes in the
      volume were statistically significant only at 2mm interval (p < 0.05). The
      difference in the cross sectional area was not statistically significant at any
      interval (p > 0.05). CONCLUSION: Within the limits of this study the rotary
      Nickel Titanium Path Files appeared to be suitable instruments for safe and easy
      creation of glide path.

PMID- 25584305
TI  - Relationship of Perceived Stress and Dental Caries among Pre University Students
      in Bangalore City.
AB  - INTRODUCTION: Stress can increase the susceptibility to dental caries by four
      possible mechanisms. Studies show that adolescents tend to more likely develop
      negative body image, disturbed eating behaviours and high levels of stress.
      Students report stress, taking and studying for exams being the greatest source
      of academic stress due to competition and the large amount of content in less
      time. AIMS AND OBJECTIVES: The objectives were to analyze the caries experience
      in relation to perceived stress during preuniversity examination period, to
      estimate the prevalence of dental caries and to calculate SiC (significant caries
      index) among preuniversity students in Marathahalli, Bangalore city, India.
      MATERIALS AND METHODS: This cross-sectional, correlational study involved 210
      students (Response rate = 65.37%). The questionnaire consisted of demographic
      details and Perceived Stress Scale (PSS). Dental caries status was evaluated
      using the WHO (1997) caries diagnostic criteria for decayed, missing, and filled
      teeth (DMFT: Dynamical mean field theory). RESULTS: Prevalence of dental caries
      was 50.48%. Mean DMFT was 1.74 and Sic index was 4.56. The correlation between
      PSS and caries experience was found to be weak (r=0.389) (p<0.001). CONCLUSION:
      Academic stress appears to affect oral health, shown by higher caries experience
      in high perceived stress score individuals.

PMID- 25584306
TI  - Bacterial Efficacy of Ca(oH)2 Against E.faecalis Compared with three Dental
      Lasers on Root Canal Dentin- An Invitro Study.
AB  - AIM: The aim of this study was to evaluate bactericidal effect of Ca(OH)2
      compared with 810 nm diode, 980 nm diode, and Nd:YAG lasers on root canal dentin
      against E.faecalis. MATERIALS AND METHODS: Sixty five freshly extracted human
      mandibular single rooted teeth were selected for the study. The apical third of
      these roots was gradually enlarged until reaching the ISO 40- K file. The samples
      were divided into 4 groups, each containing 15 teeth and 5 teeth for control
      group. Group-1: 810 nm Diode; Group-2: 980 nm Diode; Group-3: Nd:YAG; Group-4:
      Ca(OH)2. 50MUL of the E.faecalis ATCC 29212 strand was incubated in 1 mL of Brain
      Heart Infusion Broth (BHI) culture medium in37(o)C incubator for 4h. The
      concentration of the inoculation was then adjusted for a degree of turbidity
      which was adjusted to 0.5 McFarland scale. Later from the incubated broth, 10MUL
      of E.faecalis culture was inoculated into the main canal and were sealed.
      RESULTS: The incubated plates were checked for growth and the colony was counted
      using colony counter and the results are interpreted. There was statistically
      significant difference (p<0.05) amongst the Ca(OH)2 group regarding the laser
      groups. CONCLUSION: The teeth irradiated with the Nd:YAG laser had significantly
      higher bacterial reduction than all the other groups and the respective control
      groups.

PMID- 25584307
TI  - Comparison of the source of introduction to cariogenic food substance and caries
      prevalence in children.
AB  - INTRODUCTION: Dental caries being a multi-factorial disease depends on lot of
      factors. Since awareness and exposure seems to have increased, in the present
      scenario it is difficult to assume that one particular source would increase the
      occurrence of dental caries. Children are exposed to different media sources and
      spend most of their free time watching them. They are attracted by messages of
      advertisers' and susceptible to stylish advertisements of foods often harmful to
      oral and general health. AIM: To compare the effects of three different sources
      of introduction to cariogenic food substance among school children and their role
      in caries prevalence. MATERIALS AND METHODS: A total of 300 school children were
      selected for the study and a questionnaire was prepared keeping in mind the
      various sources introducing cariogenic foods to children namely television
      advertisement, magazines/news paper, posters/banners. Following which oral
      examination will be done to determine the number of carious lesions in the
      subjects. The data will be acquired, computed and statistically analysed to
      compare the correlation between these sources and caries prevalence. RESULTS:
      Children who watched television advertisements and asked for food items and soft
      drinks were found to have more caries and DMFT/dmft index. CONCLUSION: A total
      ban on advertisements would not be practically possible. A more realistic
      approach would be to limit the number of advertisements that feature potentially
      cariogenic and unhealthy food products, and also ensure that they ideally carry
      statutory warnings.

PMID- 25584308
TI  - Gender determination using diagonal measurements of maxillary molar and canine
      teeth in davangere population.
AB  - BACKGROUND: Mesiodistal and buccolingual measurements of the teeth have been the
      traditional means of determining gender which sometimes are difficult to measure.
      AIMS AND OBJECTIVES: To assess the degree of sexual dimorphism in upper permanent
      canines and first molars using diagonal diameters and to evaluate the
      applicability of diagonal measurements in sex determination. MATERIALS AND
      METHODS: Mesiobuccal-distolingual (MBDL) and distobuccal-mesiolingual (DBML)
      measurements of the crown and cervix of maxillary canine and maxillary molar were
      taken using digital vernier callipers in 100 upper dental casts obtained from 50
      males and 50 females of the age group of 17-25 y. RESULTS: With step wise
      discriminant function analysis, results were statistically significant with males
      showing higher diagonal measurement values. The classification accuracy for males
      was 69% and in females was 73% with overall accuracy of 71%. RESULTS showed that
      canines exhibited highest accuracy with cervical measurements being more
      dimorphic. MBDL measurements were found to be more reliable. Most
      dimorphicmeasurements included right molar cervical MBDL, left molar cervical
      MBDL followed by right and left molar crown MBDL. CONCLUSION: In cases of tooth
      rotations, crowding, certain fillings and attritions where traditional mesio
      distal and bucco-lingual measurements are not applicable, diagonal measurements
      could be of help in predicting gender.

PMID- 25584309
TI  - Comparative efficacy of oil pulling and chlorhexidine on oral malodor: a
      randomized controlled trial.
AB  - BACKGROUND: Oral malodor affects a large section of population. Traditional
      Indian folk remedy, oil pulling not only reduces it but can also bring down the
      cost of treatment. AIMS: To compare the efficacy of oil pulling and chlorhexidine
      in reducing oral malodor and microbes. MATERIALS AND METHODS: Three week
      randomized controlled trial was conducted among 60 students of three hostels of
      Maharani College of science and arts and commerce and Smt V.H.D.College of Home
      Science. The hostels were randomized into two intervention groups namely
      chlorhexidine group, sesame oil and one control (placebo) group. Twenty girls
      were selected from each hostel based on inclusion and exclusion criteria.
      Informed consent was obtained. The parameters recorded at the baseline (day 0)
      and post intervention on day 22 were plaque index (PI), gingival index (GI),
      objective (ORG1) and subjective (ORG2) organoleptic scores and anaerobic
      bacterial colony (ABC) count. Intra and inter group comparisons were made using
      Kruskal Wallis test, Wilcoxan sign rank test, ANOVA and student t-test. RESULTS:
      There was significant reduction (p<0.05) in the mean scores of all the parameters
      within sesame oil and chlorhexidine group. Among the groups significant
      difference was observed in objective and subjective organoleptic scores. Post hoc
      test showed significant difference (p<0.000) in mean organoleptic scores of
      sesame oil and placebo and chlorhexidine and placebo group. No significant
      difference (p<0.05) was observed between sesame oil and chlorhexidine group.
      CONCLUSION: Oil pulling with sesame oil is equally efficacious as chlorhexidine
      in reducing oral malodor and microbes causing it. It should be promoted as a
      preventive home care therapy.

PMID- 25584310
TI  - The Effect of Scaling and Root Planing on Glycaemic Control, Periodontal Status
      and Gingival Crevicular Fluid TNF-alpha Levels in an Indian Population- To Reveal
      the Ambivalent Link.
AB  - CONTEXT: Periodontal disease and diabetes mellitus(DM) share a two - way
      relationship. It can be hypothesized that successful management of periodontal
      infection in diabetes will lead not only to reduction of local signs and symptoms
      of the disease, but also to better control of glucose metabolism. AIMS: To
      monitor the effect of Scaling and Root planing (SRP) on glycaemic control in
      patients with type 2 diabetes mellitus by estimating the HbA1c and GCF TNF-alpha
      levels. SETTINGS AND DESIGN: This Interventional clinicobiochemical study was
      carried out over a period of 6 months from December 2010-May 2011 in Bengaluru,
      Karnataka, India. MATERIALS AND METHODS: Fifteen well-controlled, 15 moderately
      controlled and 15 poorly controlled diabetic subjects were enrolled in this
      study. All participants were subjected to non-surgical periodontal (SRP) therapy.
      GCF sampling and clinical periodontal parameters assessment were done at baseline
      and 3 months post-therapy. TNF-alpha levels in GCF were analyzed by enzyme-linked
      immunosorbent assay (ELISA) at baseline and 3 months post therapy. The
      improvement in glycaemic control was assessed using HbA1c levels at 3 months
      reevaluation. STATISTICAL ANALYSIS: The data obtained were statistically analysed
      using Kruskal-Wallis test, Mann-Whitney test and Wilcoxon Signed Rank test.
      RESULTS: Following periodontal treatment, all patients demon- strated a
      significant improvement in periodontal status. A reduction in TNF-alpha level and
      the HbA1c values were also observed. CONCLUSION: The result indicates that SRP is
      effective in improving metabolic control in Type 2 Diabetes Mellitus patients
      possibly through the reduction of TNF-alpha which in turn might improve the
      insulin resistance.

PMID- 25584311
TI  - Quantification of Plasma Fibrinogen Degradation Products in Areca Nut Chewers
      with and without Oral Submucous Fibrosis.
AB  - INTRODUCTION: Fibrinogen degradation products (FDPs) are the products that are
      released from fibrin/fibrinogen. Recently, it has been observed that these FDPs
      have been identified in the plasma of OSMF patients. Areca nut being the major
      aetiological agent for OSMF may play a role in the increased plasma levels of
      FDPs in OSMF. AIM: The aim of this study was to quantify the plasma FDPs levels
      in the individuals with the habit of areca nut chewing with and without OSMF.
      MATERIALS & METHODS: Total of 95 subjects were included,35 subjects with the
      habit of areca nut chewing with OSMF, 30 with the habit of areca nut chewing
      without OSMF, 30 without any habit of areca nut chewing without OSMF (control
      group). Five ml of venous blood was withdrawn from all the subjects and plasma
      FDP levels were estimated. RESULTS: Plasma FDPs were detected in all the subjects
      of OSMF but could not be detected in other two groups. As the clinical grades of
      OSMF increased, levels of plasma FDPs also increased. CONCLUSION: When plasma FDP
      increases, fibrin deposition also increases. This strengthens the finding that
      these FDPs may be an early indicator of the OSMF.

PMID- 25584312
TI  - Detection of rankl positive cells in gingival tissue in healthy & chronic
      periodontal disease patients-a comparative study.
AB  - Aim & Objective: The receptor activator of NF-kappa B ligand (RANKL) and its
      decoy receptor, osteoprotegerin (OPG), are the important proteins implicated in
      osteoclastogenesis. This study aimed to identify & quantify RANKL positive cells
      in gingival tissues in healthy & diseased patients & the study looks for
      immunohistochemical evidence of the expression of the protein in gingival tissue
      samples. MATERIALS AND METHODS: Patients were randomly selected. Thirty subject
      each for (test & control). Age range of 25-55y, either sex was selected. Tissue
      samples were collected from Control - Healthy Gingiva & Test-Chronic
      Periodontitis Patients. Tissue sections were prepared. An Immunohistochemical
      analysis was done & cell counting was done for RANKL positive cells. RESULTS:
      Immunohistochemical staining showed that RANKL-positive cells were significantly
      distributed in the inflammatory epithelium & connective tissue zone of diseased &
      non-diseased gingiva. RANKL, positive cells was increased significantly in
      patients with chronic periodontitis (p < 0.05). CONCLUSION: These findings imply
      that in this comparative study of gingival tissue for, RANKL positive cells,
      these cells were present in both healthy & chronic periodontitis samples, but
      number of positive cells present is significantly increased in chronic
      periodontitis.

PMID- 25584313
TI  - Comparision of Immunohistochemical Expression of CD10 in Odontogenic Cysts.
AB  - BACKGROUND: Expression of CD10 has been documented in various tumors like
      nasopharyngeal carcinoma, gastric carcinoma, squamous cell carcinoma, odontogenic
      tumors. AIM: To evaluate and compare CD10 expression in odontogenic cysts like
      radicular cyst, dentigerous cyst and odontogenic keratocyst (OKC). MATERIALS AND
      METHODS: Total 60 cases were included in the study, comprising 20 cases each of
      radicular, dentigerous and odontogenic keratocyst. Each case was evaluated and
      compared for immunohistochemical expression of CD10. RESULTS obtained were
      statistically analysed using ANOVA test followed by post hoc test Tukey-Kramer
      Multiple Comparisons Test for continuous variable and Chi-square test for
      discrete variable. RESULTS: More number of cases showing sub-epithelial stromal
      CD10 expression were found in OKC among the cysts. CONCLUSION: CD10 expression
      was more in OKC compared to radicular and dentigerous cysts.

PMID- 25584314
TI  - Evaluating Student's Perceptions of the Learning Environment in an Indian Dental
      School.
AB  - OBJECTIVE: To evaluate student's perception of the learning environment in a
      private dental institute in India based on DREEM inventory. MATERIALS AND
      METHODS: This cross-sectional study included students in all four years of the
      undergraduate dental course of Panineeya Institute of Dental Sciences and
      Hospital, Hyderabad, India. Self-administered Dundee Ready Education environment
      Measure (DREEM) inventory consisting of 50-items on a five-point Likert scale was
      utilized to assess the students' perceptions regarding learning environment in
      this academic dental school. Comparison for the total and domain DREEM score
      means was carried out via independent t-test for dichotomous variables (gender)
      and ANOVA for more than two variables (year of study). Significant difference was
      noted for p < 0.05. RESULTS: The response rate for this study was 86.8%. Mean age
      of the study participants was 19.61 + 1.50 y. The overall DREEM score for this
      population was 125.24 + 21.10 reflecting a more of positive than negative
      education environment in this institution. When individual domain scores were
      accounted, except for the domain SAS, females had a higher mean scores for all
      domains which was however statistically significant only for the domains SPL (p =
      0.03) and SPT (p = 0.01). Likewise, significant differences were also noted for
      SPL and SPT based on the year of study, wherein for both the domains, third year
      students had significantly higher mean scores and least was recorded for fourth
      year students. Correlation of the various domains demonstrated significant
      positive correlation among the domains. CONCLUSION: Overall this sample of dental
      students rated the learning environment in this dental institute as positive.

PMID- 25584315
TI  - Clinical evaluation of autologous platelet rich fibrin in horizontal alveolar
      bony defects.
AB  - BACKGROUND: Horizontal bone loss is the most common periodontal problem
      confronting the clinician but has received little attention. Platelet rich fibrin
      (PRF) is a second generation platelet concentrate. The platelets, leucocytes,
      growth factors and cytokines contained within PRF make it a healing biomaterial
      with tremendous potential for bone and soft tissue regeneration. AIM: This
      interventional clinical trial evaluates the clinical effectiveness of Autologous
      Platelet Rich Fibrin (PRF) in the management of horizontal bony defects. SETTINGS
      AND DESIGN: Department of Periodontics. Design was Non Randomized Clinical Trial
      with split mouth design. MATERIALS AND METHODS: A total of 45 sites with
      horizontal bone loss in 15 patients were studied, 15 sites were treated with PRF
      gel (experimental group I) and 15 sites were treated with PRF gel and PRF
      membrane (experimental group II). Control group (15 sites) were treated with open
      flap debridement. STATISTICAL ANALYSIS: All the parameters were assessed at
      baseline and after nine months which included Pocket Depth (PD), Clinical
      Attachment level (CAL), Gingival Recession (REC) and Relative Crest Height (RCH).
      The mean changes at baseline and after 9 months within each group were compared
      using Wilcoxon Signed Ranks Test. The mean changes for each parameter between
      groups were compared using Kruskal Wallis Test. RESULTS: Re-evaluation at nine
      months revealed that all groups showed a significant reduction in probing depth
      (1.1+/-0.38 mm in control, 1.73+/-0.53 mm in group I, 1.7+/-0.45 mm in group
      II)(p<0.05) and clinical attachment gain (0.86+/-0.58 mm in control, 1.56+/-0.62
      mm in group I, 1.7+/-0.52 in group II)(p<0.05) as compared to baseline.
      Intergroup comparisons of reduction in probing depth and clinical attachment gain
      showed significant differences in the experimental groups as compared to control
      (p<0.05), but there was no significant difference between the experimental groups
      (p>0.05). There was no significant difference in gingival recession and
      radiographic bone levels at 9 months post surgery (p>0.05) in all the three
      groups. CONCLUSION: Within the limitations of this study, it can be concluded
      that, clinically the use of PRF in both gel and membrane form is more effective
      than open flap debridement alone in the management of horizontal periodontal
      defects at nine months post surgery.

PMID- 25584316
TI  - Molecular Docking Study for Inhibitors of Aggregatibacter actinomycetamcomitans
      Toxins in Treatment of Aggressive Perioodontitis.
AB  - INTRODUCTION: Periodontitis is a chronic inflammatory disease of the periodontal
      tissues causing periodontal attachment loss and destruction of the alveolar bone
      which leads to mobility and loss of teeth. Aggregatibacter actinomycetemcomitans
      (Aa) is a gram negative, capnophilic, coccobacillus that plays an important role
      in aggressive Periodontitis. Aa produces a variety of virulence factors that
      facilitate the colonization, invasion and destruction of the periodontal tissues.
      Leukotoxin and cytolethal distending toxin (Cdt) are most important virulence
      factors of Aa. MATERIALS AND METHODS: The three dimensional structure of
      leukotoxin was derived by Easy modeller software and Cdt was retrieved from RCSB
      database. The possible binding sites of toxins were searched using binding site
      prediction tool Q site finder. A total of 1000 ligands of flavanol derivatives
      were generated with the help of software ACD chemsketch. Rapid virtual screenings
      of these compounds were performed in the docking tool iGEMDOCK v2.0. Based on the
      binding energy, six ligands were selected for the further study. The selected six
      ligands were then analysed for drug relevant properties based on "Lipinski's rule
      of five" and other drug like properties. The accurate docking of six ligands was
      performed using docking tool iGEMDOCK v2.0. RESULTS: From the present study, it
      has been found that carboxyl {(2R,3R)-3,7 dihydroxy 4-oxo-2(3,4,5
      trihydroxyphenyl)-3,4-dihydro2H-chromen-5-yl} oxonium, which is a novel compound
      can effectively act as an inhibitor for both the toxins. CONCLUSION: The
      leucotoxin and cytolethal distending toxin of Aa is found to be the major
      virulence factors involved in the causation of aggressive periodontitis. Hence
      the inhibitors of these toxins can be an effective drug in treatment of
      aggressive periodontitis.

PMID- 25584317
TI  - Prevalence of Gingivitis among Children of Urban and Rural Areas of Bhopal
      District, India.
AB  - BACKGROUND: Gingivitis is inflammation of the soft tissue without apical
      migration of the junctional epithelium. Redness, oedema and bleeding on probing
      characterize this condition. Untreated cases may lead to a more complex and
      destructive entity known as chronic periodontitis. Periodontitis are the main
      cause of tooth loss. Poor oral health has thus the potential of hampering the
      quality of life. So the aim of this study was to find the prevalence of
      gingivitis, among school-going children of urban and rural areas of Bhopal
      district, India. MATERIALS AND METHODS: The present descriptive, cross-sectional
      study was conducted among 12 & 15 y old middle and high school government rural
      and urban school children of Bhopal district. It was conducted of a period of two
      months. 1100 Children were examined by using WHO (modified) oral health
      assessment form, Loe and Silness index was used for recording gingival status.
      For statistical analysis SPSS version 20 was used. The chi-square test was
      applied for categorical data. p<0.05 was considered statistically significant.
      RESULTS: Prevalence of gingivitis was 59% found. 584 (53.09 %) children had mild
      gingivitis,61(5.5%) children had moderate gingivitis. CONCLUSION: This indicates
      the need for community health activities and awareness program.

PMID- 25584318
TI  - A comparative study on diagnostic accuracy of colour coded digital images, direct
      digital images and conventional radiographs for periapical lesions - an in vitro
      study.
AB  - OBJECTIVES: The identification and radiographic interpretation of periapical bone
      lesions is important for accurate diagnosis and treatment. The present study was
      undertaken to study the feasibility and diagnostic accuracy of colour coded
      digital radiographs in terms of presence and size of lesion and to compare the
      diagnostic accuracy of colour coded digital images with direct digital images and
      conventional radiographs for assessing periapical lesions. MATERIALS AND METHODS:
      Sixty human dry cadaver hemimandibles were obtained and periapical lesions were
      created in first and second premolar teeth at the junction of cancellous and
      cortical bone using a micromotor handpiece and carbide burs of sizes 2, 4 and 6.
      After each successive use of round burs, a conventional, RVG and colour coded
      image was taken for each specimen. All the images were evaluated by three
      observers. The diagnostic accuracy for each bur and image mode was calculated
      statistically. RESULTS: Our results showed good interobserver (kappa > 0.61)
      agreement for the different radiographic techniques and for the different bur
      sizes. Conventional Radiography outperformed Digital Radiography in diagnosing
      periapical lesions made with Size two bur. Both were equally diagnostic for
      lesions made with larger bur sizes. Colour coding method was least accurate among
      all the techniques. CONCLUSION: Conventional radiography traditionally forms the
      backbone in the diagnosis, treatment planning and follow-up of periapical
      lesions. Direct digital imaging is an efficient technique, in diagnostic sense.
      Colour coding of digital radiography was feasible but less accurate however, this
      imaging technique, like any other, needs to be studied continuously with the
      emphasis on safety of patients and diagnostic quality of images.

PMID- 25584319
TI  - An in Vitro Evaluation of Antimicrobial Efficacy of 2% Chlorhexidine Gel,
      Propolis and Calcium Hydroxide Against Enterococcus faecalis in Human Root
      Dentin.
AB  - AIM: To evaluate in vitro the antimicrobial efficacy of 2% Chlorhexidine gel,
      Propolis and Calcium hydroxide against Enterococcus faecalis in human root
      dentin. METHODOLOGY: One hundred and twenty human extracted anterior teeth were
      decoronated below CEJ and the apical part of root was removed to obtain 6mm of
      middle of the root. GG no 3 was used to standardize the internal diameter of root
      canal. Dentin blocks were infected with E faecalis for 21 d. They were assigned
      into four groups (n = 30).Group 1, Saline (negative control); Group 2, Propolis;
      Group 3, 2% CHX; Group 4, Calcium hydroxide, At the end of 1, 3, and 5 days an
      assessment of microbial cells was carried out at a depth of 400 MUm and colony
      counts were calculated.The data were analysed statistically with one-way analysis
      of variance followed by Scheffe multiple comparison test (p < 0.05). RESULTS: The
      number of colony-forming units was significantly lower in all experimental groups
      compared to the control group - Saline. 2% Chlorhexidinegluconate produced better
      antimicrobial efficacy (100%) on day 1, 3 and 5. Propolis (66.37%) had greater
      antimicrobial activity than Calcium hydroxide (50.89%) on day 1 but there was no
      significant difference in their antimicrobial activities on day 3 and day 5.
      CONCLUSION: 2% Chlorhexidine gel showed the maximum antimicrobial activity
      against E faecalis and Calcium hydroxide the least. Propolis can be used as an
      effective alternative intracanal medicament.

PMID- 25584320
TI  - Recurrent aphthous ulcers among tobacco users- hospital based study.
AB  - CONTEXT: Current evidence shows ambiguous relationship between tobacco use and
      the occurrence of aphthous. OBJECTIVES: We studied the relationship between the
      occurrence of recurrent aphthous ulcers and various forms of tobacco usage.
      MATERIALS AND METHODS: A hospital based case control study was carried out in a
      dental teaching hospital in Cochin, India. One hundred and two outpatient
      subjects (Males 56.9%) were identified having aphthous ulceration using Natha's
      diagnostic criteria and were classified as cases. One hundred and eight subjects
      (Males, 70.4%) with no aphthous ulceration were selected randomly as controls.
      Exposure ascertainment of tobacco usage was done by structured interview.
      RESULTS: The adjusted odd ratio was found to be 0.41 (95% CI 0.19-0.87) for
      tobacco usage and occurrence of aphthous ulceration compared to non tobacco
      users. The odds ratio of 0.41 for tobacco usage infers that subjects using
      tobacco were 59% less likely to have aphthous ulcerations compared to nontobacco
      users. CONCLUSION: The tobacco consumers have less frequency of aphthous
      ulceration compared non users.

PMID- 25584321
TI  - Assessment of Photodynamic Therapy (PDT) in Disinfection of Deeper Dentinal
      Tubules in a Root Canal System: An In Vitro Study.
AB  - CONTEXT: The success of endodontic treatment therapy depends on how well we
      eliminate pathogenic microflora from the root canal system as micro organism as
      the major cause of root canal infection. Conventional root canal treatment can
      fail if microorganisms cannot be removed sufficiently by thorough cleaning,
      shaping of root canal. Newer modalities such as photodynamic therapy are being
      tried now a days for disinfection of root canals. Aim & Objectives: The basic aim
      of this study was assessment of the antimicrobial efficacy of Photodynamic
      Therapy in deeper dentinal tubules for effective disinfection of root canals
      using microbiological and scanning electron microscopic examination in vitro.
      MATERIALS AND METHODS: The study was conducted at Teerthanker Mahaveer Dental
      College & Research Centre. The teeth required for study was collected from
      Department of Oral and Maxillofacial Surgery. Only freshly extracted 20 intact,
      non carious single rooted teeth which were indicated for orthodontic treatment
      were taken for this study. Statistical analysis was done using Student's Unpaired
      t-test were at (p<0.001) was found to be highly significant. Microbiological
      examination of samples were done and colony forming units were counted to assess
      the disinfection potential of photodynamic therapy. Scanning electron microscopic
      examination of samples was done to check penetration of bacteria's into deeper
      dentinal tubules. RESULTS: On examination, there was a marked reduction in
      microbial growth after use of photodynamic therapy. On scanning electron
      microscopic examination, it was observed that there were less number of
      bacteria's in deeper dentinal tubules in case of PDT group as compared to control
      group. CONCLUSION: The results of the present study indicate that PDT can be
      effectively used during antimicrobial procedures along with conventional
      disinfection procedure for sterilization of root canals.

PMID- 25584322
TI  - Dental Camp Experience in Lifeline Express (LLE) Train among Rural Population of
      Central, India.
AB  - INTRODUCTION: The lifeline express is the world's first hospital train. To date,
      over 800,000 patients living in the remote rural interiors of India where medical
      facilities are scarce, have been treated. OBJECTIVE: To evaluate the application
      and feasibility of providing screening, diagnosis, preventive dental treatment
      for rural population through mobile dental unit in lifeline express train from
      last three years in Madhya Pradesh, India. MATERIALS AND METHODS: The study was
      retrospective and the data was extracted from six dental camps which have been
      conducted by Life line Express/ Impact India foundation in between 2011 to 2013
      in rural and remote area of Madhya Pradesh. RESULTS: Out of six dental camps
      14,081 patients were registered and 6,526 received dental treatment. The type of
      dental treatment like extractions (3,441), scaling (2,119) and restoration (966)
      were performed. CONCLUSION: The study shows a mobile dental hospital like LLE can
      provide an excellent opportunity for rural populations regarding oral health
      care.

PMID- 25584323
TI  - Vascular endothelial growth factor levels in gingival crevicular fluid before and
      after periodontal therapy.
AB  - INTRODUCTION: Of the various cytokines and growth factors regulating
      angiogenesis, the most potent agent acting on vascular endothelium is vascular
      endothelial growth factor(VEGF). The present study aims to access VEGF
      concentration in periodontal diseases and the effect of periodontal therapy on
      its concentration in gingival crevicular fluid (GCF). MATERIALS AND METHODS:
      Ninety five subjects (47 females and 48 males) 25- 47 y of age were divided into
      healthy (group-1), gingivitis (group-2), and periodontitis (group-3). GCF samples
      were collected using micro-capillary pipettes & were transferred immediately to
      plastic vials and stored at -70C until the time of the assay. The concentration
      of VEGF was determined using commercially available ELISA kit. RESULTS: The mean
      VEGF concentration was highest in periodontitis patients (Group 3) (88.08+/
      8.04pg/ml), with lowest in healthy patients (Group 1). VEGF levels reduced
      significantly after therapy in Groups 2 and 3. CONCLUSION: VEGF levels in GCF had
      a significant correlation with both periodontal disease progression and healing
      after therapy.

PMID- 25584324
TI  - Association of root caries with oral habits in older individuals attending a
      rural health centre of a dental hospital in India.
AB  - BACKGROUND: Many risk factors can compromise an older adult's systemic health.
      Among the oral ailments in the elderly, root caries is a significant one which
      causes tooth loss in them. Hence, there is a need to have a baseline data for
      understanding problem of root caries in elderly population and factors which
      affect its prevalence. AIMS: a)To asses the prevalence of root caries in older
      individuals in a rural health centre in India. b) To asses the relationship of
      oral habits with root caries. MATERIALS AND METHODS: The study included 210
      elderly dentate and consenting individuals (123-females, 87-males) aged 55 to 75
      y and above. Demographic and health behaviour data were collected through
      personal interviews. The subjects were examined for root caries. Statistical
      analyses of the data were done using chi-square and multiple logistic regression
      analysis. RESULTS: Out of all, 94.76% of elderly patients examined had gingival
      recession in one or more teeth. The prevalence of root caries was 41.9%. The
      prevalence of root caries was significantly associated with age, perceived
      dryness of mouth, smoking, smoking and tobacco chewing and tobacco chewing only
      (p<0.05). There was significantly higher root caries in the age group of 75 years
      and above (OR-3.67). CONCLUSION: It was evident from our study that root caries
      prevalence was high in elderly population. Age, root surfaces with recession,
      deleterious oral habits such as smoking, tobacco chewing, and dryness of mouth
      had a definite effect on the prevalence of root caries.

PMID- 25584325
TI  - Comparative evaluation of microleakage of lingual retainer wires bonded with
      three different lingual retainer composites: an in vitro study.
AB  - OBJECTIVE: To evaluate microleakage when two types of retainer wires were bonded
      with two light cured and a self cured lingual retainer composites. MATERIALS AND
      METHODS: Total 120 freshly extracted human mandibular incisor teeth were
      collected and separated into six subgroups of 20 teeth each. Two different wires,
      a 0.036 inch hard round stainless steel (HRSS) wire sandblasted at the ends and
      0.0175 inch multistranded wire bonded onto the lingual surfaces of the incisors
      with three different types of composite resins of 3M company; Concise Orthodontic
      (self-cure), Transbond XT (light-cure) and Transbond LR (light-cure). Specimens
      were further sealed with a nail varnish, stained with 0.5% basic fuchsine for 24
      hours, sectioned and examined under a stereomicroscope, and scored for
      microleakage for the enamel-composite and wire-composite interfaces. Statistical
      analysis was performed by Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: For
      HRSS wire, at the enamel-composite interface, the microleakage was least with
      Transbond LR followed by Concise Orthodontic and greatest for Transbond XT
      (p<0.05). At the wire composite interface too, the microleakage was in order of
      Transbond LR<Concise Orthodontic<Transbond XT. For the multistranded wire, at the
      enamel-composite interface, the microleakage was least with Transbond LR followed
      by Concise Orthodontic and Transbond XT (p<0.05). At the wire composite interface
      too, it was seen that microleakage was the least with Transbond LR followed by
      Concise Orthodontic and Transbond XT. CONCLUSION: Transbond LR in combination
      with 0.0175 inch multistranded wire showed least microleakage amongst the groups
      studied.

PMID- 25584326
TI  - An in Vitro Evaluation of Remineralization Potential of Novamin((r)) on
      Artificial Enamel Sub-Surface Lesions Around Orthodontic Brackets Using Energy
      Dispersive X-Ray Analysis (EDX).
AB  - OBJECTIVE: To evaluate and compare the Ca/P ratio of enamel samples around the
      orthodontic brackets for time periods of 0, 2 and 10 days in two groups (control
      group and study group). MATERIALS AND METHODS: Forty extracted teeth were
      randomly divided into control group and study group. All samples were
      demineralized and incubated in artificial saliva at 37 degrees C for a period of
      10 days after demineralization. During this phase the enamel samples in the study
      group were treated with remineralizing paste (NuproNusolution containing
      Novamin(r)-Dentsply) for 10 days. At the end of the incubation period, Ca/P
      ratios were analyzed for both the groupsby EDX analysis. Data obtained was
      subjected to statistical analysis using student t-test for paired samples and
      Student t- test for individual samples (p <= 0.05). RESULTS: It was found that
      the mean Ca/P ratio was significantly lower for the control group as compared to
      the study group (p-value < 0.05) after 10 d of incubation. CONCLUSION:
      Novamin((r)) containing remineralization toothpaste showed significant
      remineralizing potential in inhibition of artificial enamel sub-surface lesion
      around bracket after 10 days of remineralization phase. EDX element analysis was
      found to be an efficient method to quantify the changes in mineral content of a
      sample during in vitro caries studies.

PMID- 25584327
TI  - Lipid profile and metabolic syndrome status in patients with oral lichen planus,
      oral lichenoid reaction and healthy individuals attending a dental college in
      northern India - a descriptive study.
AB  - BACKGROUND: Chronic inflammation causes disturbances in the lipid metabolism.
      When this dyslipidemia becomes prolonged it increases the risk of cardiovascular
      disease. Recent literature reveals similar dyslipidemia in patients with lichen
      planus. However, the results were not compared with lichenoid reactions.
      OBJECTIVE: The aim of this study was to profile the lipid levels and metabolic
      syndrome status in patients with oral lichen planus (OLP), oral lichenoid
      reactions (OLR) and healthy individuals in order to evaluate their respective
      cardiovascular risk. MATERIALS AND METHODS: This case-control descriptive study
      included 32 adults from the OPD visiting the Department of Oral Medicine, 18 with
      either oral lichen planus or oral lichenoid reactions and 14 age and sex matched
      healthy controls. Ethical clearance and informed consent were obtained. Their
      lipid levels, body mass index and metabolic syndrome status were evaluated.
      Statistical analyses were performed with the SPSS version 16.0 software.P>=0.05
      was considered significant. RESULTS: The key findings of this study were a)
      increased levels of S.cholesterol and LDL-C in OLP and OLR patients when compared
      to normal healthy individuals b) significantly higher S.triglyceride and VLDL in
      OLP when compared to OLR and c) lower HDL-C levels in OLP when compared to OLR.
      2(18%) patients with OLP and 3(50%) with OLR were found to have high BMI
      suggestive of obesity whereas none of the normal individuals were obese.
      CONCLUSION: There may be an association between chronic inflammation and
      dyslipidemia that increases the risk for cardiovascular disease. OLP and OLR
      patients have increased serum cholesterol and LDL-C when compared to normal
      adults. Further research on lipid levels in OLR are required to establish the
      findings of this study.

PMID- 25584328
TI  - Immunolocalization of CD34 Positive Progenitor Cells in Diabetic and Non Diabetic
      Periodontitis Patients - A Comparative Study.
AB  - BACKGROUND: Little research has been documented to determine the CD34 positive
      cells in healthy periodontium, chronic periodontitis and in chronic periodontitis
      with diabetes mellitus individuals. AIM: The aim of the present study was to
      evaluate and compare the CD34 positive progenitor cells of the gingiva in
      patients with healthy periodontium, chronic periodontitis and chronic
      periodontitis with Diabetes Mellitus. MATERIALS AND METHODS: A total number of 75
      patients were divided into 3 groups which included Group I (healthy
      periodontium), Group II (chronic periodontitis) and Group III (chronic
      periodontitis with diabetes mellitus). Periodontal examination included Plaque
      index, Gingival index, Gingival bleeding index, Probing pocket depth and Clinical
      attachment levels. Gingival biopsies were collected from each participant and
      they were fixed in formalin embedded in paraffin which was later subjected to
      immunohistochemical procedure with anti-CD34 (a stemness marker). T-Test and
      Regression analysis (R-square) was used to analyse the data. RESULTS: The mean
      number of CD34 positive cells were higher in group III (5.71+/-1.97) compared to
      Group chronic periodontitis group I (4.98+/- 2.08) and II (4.48+/- 1.24).
      CONCLUSION: Although CD34 is a non specific stemness marker, results suggest that
      there is a significant difference in the number of CD34 positive progenitor cells
      between Group II and Group III but no significant difference was observed between
      Group I, II and Group I, III.

PMID- 25584329
TI  - Lamellar Icthyosis - A case Report.
AB  - Autosomal recessive congenital ichthyosis is a heterogenous group of disorders
      that are present at birth with generalized involvement of skin and lack of other
      organ systems. Clinical presentation, pattern of inheritance, and laboratory
      evaluation may establish a precise diagnosis, which can assist in prognosis and
      genetic counseling. There is a little knowledge about the oral manifestations of
      these disorders.This case report presents management and complete oral
      rehabilitation of a rare case of lamellar ichthyosis. 

PMID- 25584330
TI  - Kabuki Make-up Syndrome - A Case Report with Electromyographic study.
AB  - Kabuki make-up syndrome (KMS), also called Niikawa-Kuroki syndrome reported in
      1981, is a rare congenital disorder of unknown aetiology. It is know to occur in
      many other ethnic groups, though initially described in Japan. We report a 24
      year-old girl of Asian origin diagnosed with Kabuki syndrome based on
      characteristic clinical features. It is characterized by distinctive facial
      features (eversion of the lower lateral eyelid, arched eyebrows with the lateral
      one-third dispersed or sparse, depressed nasal tip, and prominent ears), skeletal
      anomalies, Dermatoglyphic abnormalities, short stature. As per our knowledge
      there is no literature which gives information about the importance of
      electromyographic study in the diagnosis and treatment of the KMS. Hence, this
      report emphasizes on the role of the same. 

PMID- 25584331
TI  - Idiopathic orofacial granulomatosis - a diagnostic and treatment challenge.
AB  - Orofacial granulomatosis is an uncommon disease, usually presenting as recurrent
      or persistent swelling of the soft tissues, predominantly lips - termed as
      Cheilitis Granulomatosa. Though various aetiological factors like foreign body
      reactions, infections, Crohn's disease and Sarcoidosis have been implicated in
      the disease process. Delayed Hypersensitivity reaction with a predominant Th1
      mediated immune response provide further evidence to the etiopathogenesis in
      Orofacial granulomatosis. The term Idiopathic Orofacial Granulomatosis is used in
      cases with unknown aetiology. This case report describes Idiopathic Orofacial
      granulomatosis in a 25-year-old male patient with persistent upper lip swelling
      and gingival enlargement. Management with intralesional triamcinolone acetonide
      40mg, twice a week for three weeks, resulted in significant remission without
      recurrence after a eight month follow up. 

PMID- 25584332
TI  - Biologic restoration: a treatment option for reconstruction of anterior teeth.
AB  - Several procedures are advised to manage fractured anterior tooth structure using
      acrylic resin, composite restoration, ceramic or metal crown with ceramic facing.
      Biologic restoration is a procedure to restore fractured tooth structure with
      natural tooth material. In this in vitro case we have made an attempt for
      aesthetic rehabilitation of maxillary central incisor with similar biologic crown
      taken form extracted maxillary central incisor. It was observed that biologic
      restoration is an aesthetic, economical, fast and functional procedure which can
      be used as an alternative method to restore fractured primary or permanent
      anteriors. 

PMID- 25584333
TI  - Remedy for repeated implant retained denture fracture-a challenging case report.
AB  - The most common site of fracture in a maxillary or a mandibular complete denture
      is along an anteroposterior line that coincides with the labial notch in in the
      denture which used to provide the frenum relief. Osseointegrated implants have
      been a boon to the patients who are completelly edentulous and are not satisfied
      with the conventional removable complete denture approach.Implant supported
      dentures have proven to provide superior retention and support for removable
      complete dentures. Nevertheless, fracture of the denture bases is a common
      complication of implant-supported mandibular overlay dentures,ecspecially when
      the artificial denture is opposing natural dentition. This article describes and
      illustrates a method of reinforcing implant-supported mandibular overdentures to
      overcome this problem. 

PMID- 25584334
TI  - Extramedullary plasmacytoma of gingiva and soft tissue in neck.
AB  - Plasmacytoma is a malignant disease that present either in bone marrow (medullary
      plasmacytoma), within the bone (solitary plasmacytoma of bone), or outside of
      bone, as the extramedullary plasmacytoma. Extramedullary plasmacytoma accounts
      for 3% of all plasma cell tumours and approximately 90% of extramedullary
      plasmacytomas affect the head and neck region commonly affecting the nasal
      cavity, paranasal sinuses, tonsillar fossa and oral cavity. Multiple
      extramedullary plasmacytoma is defined when there is more than one extramedullary
      tumour of clonal plasma cells and such presentations are extremely rare. We
      report such a rare case of multiple extramedullary plasmacytoma involving gingiva
      and neck. Here is a case report of a 65-year-old female patient presenting with
      extramedullary plasmacytoma of the gingiva and soft tissue in neck. 

PMID- 25584335
TI  - Orbito-rhino-antro access osteotomy for anterior skull base lesions.
AB  - Even with advent of endoscopic assisted surgeries the access osteotomy plays an
      important role for accessing the pathological lesions of anterior skull base
      since beginning of the era of surgery. This report introduces the orbito-rhino
      antral access osteotomy for the removal of juvenile nasio angio fiboma extending
      in to the cranial base. This osteotomy provides good access to the lesion with
      lesser morbidity and without hampering the occlusion as in lefort osteotomies. It
      is safe, easy and faster to perform. Osteotomised segment is easy to replace and
      gives ease for the surgeon to access without any hindrance. The osteotomised
      segment act as free graft and there are no complications postoperatively even
      after 48 mnth of follow-up. 

PMID- 25584336
TI  - A Novel Esthetic Approach using Connective Tissue Graft for Soft Tissue Defect
      Following Surgical Excision of Gingival Fibrolipoma.
AB  - The aim of the present case report is to evaluate the adjunctive use of a
      connective tissue graft to overcome soft tissue defects following excision of a
      gingival fibrolipoma in the aesthetic region. Connective tissue graft has been
      well documented for treating defects of esthetic concern. However, the literature
      does not contain many reports on the esthetic clinical outcome following the use
      of connective tissue graft secondary to excision of soft tissue tumours. A 28
      year-old male patient reported with a complaint of a recurrent growth in relation
      to his lower front tooth region. The lesion which was provisionally diagnosed as
      fibroma was treated with a complete surgical excision, following which a modified
      coronally advanced flap and connective tissue graft was adopted to overcome the
      soft tissue defect. The excised growth was diagnosed histologically as
      fibrolipoma. One year follow up showed no recurrence of the lesion and good
      esthetics.The adjunctive use of the connective tissue graft and modified
      coronally advanced flap predictably yields optimal soft tissue fill and excellent
      esthetics. Hence, routine use of this procedure may be recommended for surgical
      excision of soft tissue growths in esthetically sensitive areas. 

PMID- 25584338
TI  - Extra-oral approach for removal of ectopic impacted lower third molar: a case
      report.
AB  - Extra oral approach for removal of the lower third molar is uncommon. This case
      report illustrates an example of removal of lower third molar by extra-oral
      approach preserving the inferior dental nerve. 

PMID- 25584337
TI  - Sarcoidosis presenting as isolated gingival enlargement: a rare case entity.
AB  - Sarcoidosis is a non-caseating granulomatous disease . It is a multiorgan
      inflammatory disorder of unknown etiology. Conditions affecting skin or other
      organs frequently involve oral cavity and rarely manifest as gingival disease.
      Here we are reporting a rare case in which gingival hyperplasia was the initial
      symptom which finally led to the diagnosis of sarcoidosis. Oral mucous membrane
      needs to be examined carefully as it may constitute in presenting first sign of
      systemic sarcoidosis. 

PMID- 25584339
TI  - Fibre reinforced composite: post and core material in a pediatric patient - an
      alternative to usual.
AB  - Fractured teeth are always a challenge to the dentist. The root canal therapy
      today can retain even very badly broken teeth. One of the most accepted
      techniques involve restoration of extensively carious or badly fractured teeth by
      the fabrication of a post and core while utilizing the root canal space for
      anchorage. So far, the only materials that are available to the dentist for this
      procedure have been a variety of metallic alloys. These materials are hard and
      need to be cast precisely so that they can fit the canals. Today materials are
      available which usually eliminates all the intermediate steps which are done in
      laboratories and the total control is rendered in the hands of the dentist, to
      fabricate on the chair, a resilient, aesthetic and bonded post and core. One such
      material is discussed here in a pediatric permanent anterior tooth. 

PMID- 25584340
TI  - Unfolding the hidden facts of paediatric maxillofacial trauma.
AB  - Hard tissue injuries are uncommon in the paediatric patient; the paediatric
      population sustains 1 to 14.7% of all facial fractures. The management of the
      paediatric patient with maxillofacial injury should take into consideration, the
      differences in anatomy and physiology between children and adults, the presence
      of concomitant injury, the particular stage in growth and development and the
      specific injuries and anatomic sites that the injuries affect. Minimally
      displaced fractures in paediatric patients can be managed conservatively, while
      displaced fractures may require open approaches and rigid fixation. Hence, the
      present article presents an overview of the available published literature on
      maxillofacial trauma in paediatric patient. 

PMID- 25584341
TI  - SWOT Analysis of Dental Health Workforce in India: A Dental alarm.
AB  - CONTEXT: India faces an acute shortage of health personnel. Together with
      inequalities in distribution of health workers, dental health workers also become
      a part contributing to it impeding the progress towards achievement of the
      Millennium Development Goals. AIM: To assess dental health-workforce
      distribution, identify inequalities in dental health-workers provision and report
      the impact of this mal distribution in India. MATERIALS AND METHODS: Situational
      analysis done by using the primary data from the records of Dental Council of
      India. RESULTS: In India, 0.088% of dental health worker per 1000 population
      exists. Inequalities in the distribution of dentists exist in India. Certain
      states are experiencing an acute shortage of dental health personnel whereas
      certain cities are over fledged with dentists like Karnataka, Maharastra,
      Tamilnadu being states with high concentration & Jharkhand, Rajasthan,
      Uttaranchal being the least. CONCLUSION: Although the production of health
      workers has expanded greatly in recent years by increase in number of dental
      colleges the problems of imbalances in their distribution persist. In the race of
      increasing dentist population ratio in total, inequitable distribution of
      appropriately trained, motivated and supported dentists gives a mere feel of
      saturation in jobs making youngsters to not to choose dentistry as a career
      giving an alarm.

PMID- 25584342
TI  - Relation between psoriasis and geographic tongue.
AB  - The aim this article is to investigate the link between geographic tongue and
      psoriasis skin disease. Our review paper of the literature will handle strict
      study about the relation between geographic tongue and psoriasis. Our search has
      identified only limited studies available in English written literature starting
      from 2006-2013 using pubMed - indexed for MEDLINE. The result of this review
      suggests that geographic tongue may be an oral manifestation of psoriasis.There
      is no clear evidence in literature about association with gender and aetiology
      except one study which shows that benign migratory glossitis is more prevalent in
      young, nonsmoker and atopic or allergic individuals. Treatment for oral lesions
      is not standardized. A geographic tongue is significantly more frequent in
      psoriatic patients but only a limited data is available to date to strongly
      validate the association between these two entities.We recommend the general
      practitioner to have a good understanding about the clinical presentation,
      pathogenesis, diagnosis and treatment of this lesion. Psoriatic patients should
      be encouraged to undergo routine dental checkups. 

PMID- 25584343
TI  - Accidental injection of formalin: case report of severe negligence in dental
      office.

PMID- 25584344
TI  - Rehabilitation of edentulous atrophic anterior mandible - the role of vertical
      alveolar distraction osteogenesis.
AB  - The rehabilitation of patients with edentulous alveolar ridge is always a
      challenge, more so in case of a long standing atrophic mandible. Mandible, the
      largest movable bone in the maxillofacial skeleton is associated with many soft
      tissue attachments which imparts dislodging forces to prosthesis. In addition to
      this, the rate of resorption of the mandibular ridge is four times that of the
      maxilla. These factors make the environment of the mandibular arch less favorable
      to complete denture stability and retention. An ideal solution would be to
      augment the atrophic alveolar ridge with native bone of the individual which
      shall eliminate the possible complications, associated with conventional ridge
      augmentation procedures. With advent of modern technology, and increased
      biological understanding, the principles of distraction osteogenesis are
      increasingly being applied to the craniofacial skeleton and have been found to be
      a viable option in augmenting the native alveolar bone in the mandible. Here the
      application of an indigenous stainless steel vertical alveolar distraction device
      to augment atrophic anterior mandibular ridge is assessed in six patients. 

PMID- 25584345
TI  - The United States System for Training of Gastroenterologists in Oncology.
AB  - Competency for practicing gastroenterology in the United States requires
      accredited training in Internal Medicine, followed by accredited training in
      gastroenterology and hepatology. The structured training encompasses a 3-year
      period after graduation with a medical degree for internal medicine, followed by
      a 3-year period for gastroenterology and hepatology. Within the gastroenterology
      training period, competency in oncology knowledge and procedural approaches to
      luminal and solid gastrointestinal organ cancers is required, whereas knowledge
      competency but not procedural competency is required in areas of advanced
      endoscopic procedures for cancer care. Only general knowledge, but not
      competency, is required for areas such as chemotherapy, which can be obtained
      with further optional training in a structured 2-year oncology fellowship
      program. Although there is no standardization to date for including full oncology
      training within a gastroenterology training program in the United States, there
      is great interest from gastroenterology professional societies to include a
      pathway for trainees within the gastroenterology training program.

PMID- 25584346
TI  - Diabetes island: preliminary impact of a virtual world self-care educational
      intervention for african americans with type 2 diabetes.
AB  - BACKGROUND: Diabetes is a serious worldwide public health challenge. The burden
      of diabetes, including prevalence and risk of complications, is greater for
      minorities, particularly African Americans. Internet-based immersive virtual
      worlds offer a unique opportunity to reach large and diverse populations with
      diabetes for self-management education and support. OBJECTIVE: The objective of
      the study was to examine the acceptability, usage, and preliminary outcome of a
      virtual world intervention, Diabetes Island, in low-income African Americans with
      type 2 diabetes. The main hypotheses were that the intervention would: (1) be
      perceived as acceptable and useful; and (2) improve diabetes self-care (eg,
      behaviors and barriers) and self-care related outcomes, including glycemic
      control (A1C), body mass index (BMI), and psychosocial factors (ie, empowerment
      and distress) over six months. METHODS: The evaluation of the intervention impact
      used a single-group repeated measures design, including three assessment time
      points: (1) baseline, (2) 3 month (mid intervention), and (3) 6 month (immediate
      post intervention). Participants were recruited from a university primary care
      clinic. A total of 41 participants enrolled in the 6 month intervention study.
      The intervention components included: (1) a study website for communication,
      feedback, and tracking; and (2) access to an immersive virtual world (Diabetes
      Island) through Second Life, where a variety of diabetes self-care education
      activities and resources were available. Outcome measures included A1C, BMI, self
      care behaviors, barriers to adherence, eating habits, empowerment, and distress.
      In addition, acceptability and usage were examined. A series of mixed-effects
      analyses, with time as a single repeated measures factor, were performed to
      examine preliminary outcomes. RESULTS: The intervention study sample (N=41)
      characteristics were: (1) mean age of 55 years, (2) 71% (29/41) female, (3) 100%
      (41/41) African American, and (4) 76% (31/41) reported annual incomes below US
      $20,000. Significant changes over time in the expected direction were observed
      for BMI (P<.02); diabetes-related distress (P<.02); global (P<.01) and dietary
      (P<.01) environmental barriers to self-care; one physical activity subscale
      (P<.04); and one dietary intake (P<.01) subscale. The participant feedback
      regarding the intervention (eg, ease of use, interest, and perceived impact) was
      consistently positive. The usage patterns showed that the majority of
      participants logged in regularly during the first two months, and around half
      logged in each week on average across the six month period. CONCLUSIONS: This
      study demonstrated promising initial results of an immersive virtual world
      approach to reaching underserved individuals with diabetes to deliver diabetes
      self-management education. This intervention model and method show promise and
      could be tailored for other populations. A large scale controlled trial is needed
      to further examine efficacy.

PMID- 25584348
TI  - Adherence to informed consent standards in Shiraz hospitals: matrons'
      perspective.
AB  - BACKGROUND: Informed consent is an important part of the patients' rights and
      hospitals are assigned to obtain informed consent before any diagnostic or
      therapeutic procedures. Obtaining an informed consent enables patients to accept
      or reject their care or treatments and prevent future contentions among patients
      and medical staff. METHODS: This survey was carried out during 2011-2. We
      assessed adherence of 33 Shiraz hospitals (governmental and non-governmental) to
      informed consent standards defined by Joint Commission International (JCI)
      Accreditation, USA. The questionnaire was designed using the Delphi method and
      then filled out by hospital matrons. We calculated valid percent frequency for
      each part of the questionnaire and compared these frequencies in governmental and
      non-governmental hospitals using analytical statistics. RESULTS: Considering 63%
      of the hospitals that filled out the questionnaire, no statistically significant
      difference was observed between the governmental and non-governmental hospitals
      in adherence to informed consent standards. CONCLUSION: This study shows a
      relatively acceptable adherence to standards about informed consent in Shiraz
      hospitals but the implementation seems not to be as satisfactory.

PMID- 25584347
TI  - Shanghai rising: health improvements as measured by avoidable mortality since
      2000.
AB  - Over the past two decades, Shanghai, the largest megacity in China, has been
      coping with unprecedented growth of its economy and population while overcoming
      previous underinvestment in the health system by the central and local
      governments. We study the evolution of Shanghai's healthcare system by analyzing
      "Avoidable Mortality" (AM) - deaths amenable to public health and healthcare
      interventions, as previously defined in the literature. Based on analysis of
      mortality data, by cause of death, from the Shanghai Municipal Center for Disease
      Control and Prevention, we analyze trends over the period 2000-10 and compare
      Shanghai's experience to other mega-city regions - New York, London and Paris.
      Population health status attributable to public health and healthcare
      interventions improved dramatically for Shanghai's population with permanent
      residency status. The age-adjusted rate of AM, per 1,000 population, dropped from
      0.72 to 0.50. The rate of decrease in age-adjusted AM in Shanghai (30%) was
      comparable to New York City (30%) and Paris (25%), but lower than London (42%).
      Shanghai's establishment of the Municipal Center for Disease Control and
      Prevention and its upgrading of public health and health services are likely to
      have contributed to the large decrease in the number and rate of avoidable
      deaths, which suggests that investments in public health infrastructure and
      increasing access to health services in megacities - both in China and worldwide 
      can produce significant mortality declines. Future analysis in Shanghai should
      investigate inequalities in avoidable deaths and the extent to which these gains
      have benefitted the significant population of urban migrants who do not have
      permanent residency status. 

PMID- 25584349
TI  - Planning and developing services for diabetic retinopathy in Sub-Saharan Africa.
AB  - BACKGROUND: Over the past few decades diabetes has emerged as an important non
      communicable disease in Sub-Saharan Africa (SSA). Sight loss from Diabetic
      Retinopathy (DR) can be prevented with screening and early treatment. The
      objective of this paper is to outline the required actions and considerations in
      the planning and development of DR screening services. METHODS: A multiple-case
      study approach was used to analyse five DR screening services in Botswana, Ghana,
      Tanzania and Zambia. Cases included: two regional screening programmes, two
      hospital-based screening services and one nationwide screening service. Data was
      collected using qualitative methodologies including: document analysis, in-depth
      interviews and observation. The World Health Organization (WHO) Health Systems
      Framework was adopted as the conceptual framework for analysis. RESULTS: Planning
      for a sustainable and integrated DR screening programme demanded a health systems
      approach. Collaboration with representatives from a variety of ministerial
      departments and professional bodies was required. Evolution of DR screening
      services may occur in a variety of ways including: increasing geographical
      coverage, integration into the general healthcare system, and stepwise
      progression from a passive, opportunistic service to one that systematically and
      proactively seeks to prevent DR. Lessons learned from the implementation of
      cervical cancer prevention programmes in resource-poor settings may assist the
      development of DR programmes in similar settings. CONCLUSION: To promote good
      planning of DR screening services and ensure limited resources are used
      effectively, there is a need to learn from screening programmes in other medical
      specialities and a need to share experiences between newly-developing DR
      programmes in resource-poor countries. The WHO Health Systems Framework presents
      an invaluable tool to ensure a systematic approach to planning DR screening
      services.

PMID- 25584350
TI  - Inequity in hospitalization care: a study on utilization of healthcare services
      in West Bengal, India.
AB  - BACKGROUND: Out of eight commonly agreed Millennium Development Goals (MDG), six
      are related to the attainment of Universal Health Coverage (UHC) throughout the
      globe. This universalization of health status suggests policies to narrow the gap
      in access and benefit sharing between different socially and economically
      underprivileged classes with that of the better placed ones and a consequent
      expansion of subsidized healthcare appears to be a common feature for most of the
      developing nations. The National Health Policy in India (2002) suggests expansion
      of market-based care for the affording class and subsidized care for the
      deserving class of the society. So, the benefit distribution of this limited
      public support in health sector is important to examine to study the welfare
      consequences of the policy. This paper examines the nature of utilization to
      inpatient care by different socio-economic groups across regions and gender in
      West Bengal (WB), India. The benefit incidence of public subsidies across these
      socio-economic groups has also been verified for different types of services like
      medicines, diagnostics and professional care etc. METHODS: National Sample Survey
      Organization (NSSO) has collected information on all hospitalized cases (60(th)
      round, 2004) with a recall period of 365 days from the sampled households through
      stratified random sampling technique. The data has been used to assess
      utilization of healthcare services during hospitalization and the distribution of
      public subsidies among the patients of different socio-economic background; a
      Benefit Incidence Analysis (BIA) has also been carried out. RESULTS: Analysis
      shows that though the rate of utilization of public hospitals is quite high,
      other complementary services like medicine, doctor and diagnostic tests are
      mostly purchased from private market. This leads to high Out-of-Pocket (OOP)
      expenditure. Moreover, BIA reveals that the public subsidies are mostly enjoyed
      by the relatively better placed patients, both socially and economically. The
      worse situation is observed for gender related inequality in access and benefit
      from public subsidies in the state. CONCLUSION: Focused policies are required to
      ensure proper distribution of public subsidies to arrest high OOP expenditure.
      Drastic change in policy targeting is needed to secure equity without
      compromising efficiency.

PMID- 25584351
TI  - Addressing geriatric oral health concerns through national oral health policy in
      India.
AB  - There is an escalating demand for geriatric oral healthcare in all developed and
      developing countries including India. Two-thirds of the world's elderly live in
      developing countries. This is a huge population that must receive attention from
      policy-makers who will be challenged by the changing demands for social and
      health services including oral health services. Resources are limited thus rather
      than being aspirational in wanting to provide all treatment needed for everybody,
      this critique presents a road map of how we might answer the present and future
      geriatric oral health concerns in a most efficient manner in a developing
      country. Viewing the recent Indian demographic profile and the trends in oral
      health, pertinent policy subjects have been discussed concerning the oral health
      needs of the elderly and also the associated challenges which include strategies
      to improve quality of life, strategies to train and educate the dental workforce
      and above all the role of healthcare systems towards realization of better aged
      society in India and other developing countries. 

PMID- 25584352
TI  - Responsibilising managers and clinicians, neglecting system health? What kind of
      healthcare leadership development do we want?: Comment on "Leadership and
      leadership development in healthcare settings - a simplistic solution to complex
      problems?".
AB  - Responding to Ruth McDonald's editorial on the rise of leadership and leadership
      development programmes in healthcare, this paper offers three arguments. Firstly,
      care is needed in evaluating impact of leadership development, since achievement
      of organisational goals is not necessarily an appropriate measure of good
      leadership. Secondly, the proliferation of styles of leadership might be
      understood in part as a means of retaining control over public services while
      distributing responsibility for their success and failure. Thirdly, it makes a
      plea for the continued utility of good administrative skills for clinicians and
      managers, which are likely to become all-the-more important given recent
      developments in healthcare policy and governance. 

PMID- 25584353
TI  - Who doesn't want to be a leader? Leaders are such wonderful people: Comment on
      "Leadership and leadership development in healthcare settings - a simplistic
      solution to complex problems?".
AB  - Leadership, as McDonald (1) argues, is a phenomenon which many people involved in
      healthcare around the globe put great emphasis on today; some even see the
      improvement of leadership as a panacea for all the ills of their healthcare
      system. This brief commentary on her work seeks to supplement the points she
      makes by emphasising the personal attractions leadership enjoys, at least in the
      eyes of many of those who exercise power in healthcare. It also endeavours to
      highlight some of the ironies and absurdities which arise as a result of the
      conflicts about what terms we should use to describe the "leaders" (or,
      alternatively perhaps, those who seek to enjoy supremacy) within healthcare. 

PMID- 25584354
TI  - Will Universal Health Coverage (UHC) lead to the freedom to lead flourishing and
      healthy lives?: Comment on "Inequities in the freedom to lead a flourishing and
      healthy life: issues for healthy public policy".
AB  - The focus on public policy and health equity is discussed in reference to the
      current global health policy discussion on Universal Health Coverage (UHC). This
      initiative has strong commitment from the leadership of the international
      organizations involved, but a lack of policy clarity outside of the health
      financing component may limit the initiative's impact on health inequity. In
      order to address health inequities there needs to be greater focus on the most
      vulnerable communities, subnational health systems, and attention paid to how
      communities, civil society and the private sector engage and participate in
      health systems. 

PMID- 25584355
TI  - Nudge, embarrassment, and restriction-replies to Voigt, Tieffenbach, and Saghai.

PMID- 25584356
TI  - Ebola treatment and prevention are not the only battles: understanding Ebola
      related fear and stigma.

PMID- 25584357
TI  - A call for a backward design to knowledge translation.
AB  - Despite several calls to support evidence-informed policy-making, variations in
      uptake of evidence into policy persist. This editorial brings together and builds
      on previous Knowledge Translation (KT) frameworks and theories to present a
      simple, yet, holistic approach for promoting evidence-informed policies. The
      proposed conceptual framework is characterized by its impact-oriented approach
      and its view of KT as a continuum from the evidence synthesis stage to uptake and
      evaluation, while highlighting capacity and resource requirement at every step. A
      practical example is given to guide readers through the different steps of the
      framework. With a growing interest in strengthening evidence-informed policy
      making, there is a need to continuously develop theories to understand and
      improve the science of KT and its implementation within the field of policy
      making. 

PMID- 25584358
TI  - Acute Retinal Necrosis with Multiple Viral Infections: A Case Report.
AB  - A 52-year-old male presented with acute retinal necrosis in his left eye. Slit
      lamp examination revealed stellate keratic precipitates and cells in the anterior
      chamber and vitreous. Funduscopy of his left eye revealed multiple yellow
      deposits. Pathological examination of the vitreous showed both small, reactive
      lymphocytes and a few macrophages. IL-6 and IFN-gamma were elevated in the
      vitreous. Microdissected macrophages from the vitreous revealed DNAs from
      multiple viruses. The patient responded to oral valacyclovir. We conclude that
      multiple viral infections can be involved in the pathogenesis of acute retinal
      necrosis and that adequate anti-viral therapy has a beneficial effect on disease
      progression. However, retinal detachment can be a consequence for a poor visual
      outcome.

PMID- 25584359
TI  - Prostaglandin I2 IP Receptor Agonist, Beraprost, Prevents Transient Global
      Cerebral Ischemia Induced Hippocampal CA1 Injury in Aging Mice.
AB  - Beraprost sodium is a new stable, orally active Prostaglandin I2 analogue. The
      aim of this study was to determine the effect of beraprost on cognitive
      dysfunction and locomotor impairment induced by bilateral common carotid artery
      occlusion in mice. We investigated the ameliorating effect of beraprost through
      PGI2 IP receptor by studying neurologic deficit assessment and T-maze testing in
      young and old male C57Bl/6 wild-type (WT) and IP receptor knockout (IP KO) mice
      following a 12 min bilateral common carotid artery occlusion (BCCAo) and 7 days
      of reperfusion. Beraprost reversed BCCAo induced cognitive impairment and
      neurological deficit in a dose dependent manner. Immunohistochemical studies
      showed attenuation of neuronal cell death, astrogliosis, microglial invasion, and
      myeloperoxidase (MPO) activity in both young and old WT mice after post treatment
      with beraprost. Moreover, after BCCAo, phosphorylated cAMP response element
      binding protein positive cell numbers were increased with beraprost treatment
      over vehicle treated controls. These results show that beraprost treatment
      attenuated cognitive dysfunction and neurological deficits induced by BCCAo, and
      suggest that this effect may be mediated by the neuroprotective effects of
      treatment.

PMID- 25584360
TI  - Nanoimaging for Molecular Pharmaceutics of Alzheimer's and other
      Neurodegenerative Disorders.

PMID- 25584362
TI  - FOXO3a: A Potential Target in Prostate Cancer.

PMID- 25584361
TI  - Role of Self-Efficacy in the Relationship Between Patient-Provider Relationships
      and Psychological Insulin Resistance Among Patients with Type 2 Diabetes.
AB  - Psychological insulin resistance (PIR) affects patients' self-care behaviors and
      quality of life due to the delay of insulin treatment for optimal glycemic
      control. Although effective patient-provider communication and relationships have
      been shown to improve patients' overall treatment adherence and attitude toward
      treatment, little is known about the potential mechanisms by which effective
      patient-provider communication and relationships decrease PIR and whether these
      relationships are mediated by diabetes self-efficacy. The purpose of this study
      is to examine whether diabetes self-efficacy among patients with type 2 diabetes
      (T2D) mediates the relationships between PIR and perceived patient-provider
      relationships. A total of 178 patients with T2D participated in a cross-sectional
      study. Data were obtained by patient interview using validated measures of
      diabetes attitude, diabetes knowledge, self-efficacy, and patient-provider
      communication. PIR was measured by using a validated measure, Barriers to Insulin
      Treatment. A structural equation model was developed to estimate direct and
      indirect effects of patient-provider relationship on PIR when self-efficacy was
      controlled as a mediator. Diabetes knowledge and attitude were not significantly
      associated with PIR. Better patient-provider relationship was directly associated
      with lower PIR (beta = -.40, p = 0.008). When diabetes self-efficacy was included
      as a mediator, the direct effect between patient-provider relationship and PIR
      changed (beta = -.27, p = 0.034), indicating that better patient-provider
      relationship that reduces PIR is due to greater diabetes self-efficacy. The
      findings suggest that development of intervention programs aimed at improving
      diabetes self-efficacy-which may be positively correlated with better patient
      provider relationship-is needed to reduce PIR.

PMID- 25584363
TI  - Gene-Gene and Gene-Environment Interactions Underlying Complex Traits and their
      Detection.

PMID- 25584364
TI  - The DISTANCE model for collaborative research: distributing analytic effort using
      scrambled data sets.
AB  - BACKGROUND: Data-sharing is encouraged to fulfill the ethical responsibility to
      transform research data into public health knowledge, but data sharing carries
      risks of improper disclosure and potential harm from release of individually
      identifiable data. METHODS: The study objective was to develop and implement a
      novel method for scientific collaboration and data sharing which distributes the
      analytic burden while protecting patient privacy. A procedure was developed where
      in an investigator who is external to an analytic coordinating center (ACC) can
      conduct original research following a protocol governed by a Publications and
      Presentations (P&P) Committee. The collaborating investigator submits a study
      proposal and, if approved, develops the analytic specifications using existing
      data dictionaries and templates. An original data set is prepared according to
      the specifications and the external investigator is provided with a complete but
      de-identified and shuffled data set which retains all key data fields but which
      obfuscates individually identifiable data and patterns; this" scrambled data set"
      provides a "sandbox" for the external investigator to develop and test analytic
      code for analyses. The analytic code is then run against the original data at the
      ACC to generate output which is used by the external investigator in preparing a
      manuscript for journal submission. RESULTS: The method has been successfully used
      with collaborators to produce many published papers and conference reports.
      CONCLUSION: By distributing the analytic burden, this method can facilitate
      collaboration and expand analytic capacity, resulting in more science for less
      money.

PMID- 25584365
TI  - Attitudinal and Intentional Acceptance of Domestic Robots by Younger and Older
      Adults.
AB  - A study was conducted to examine the expectations that younger and older
      individuals have about domestic robots and how these expectations relate to robot
      acceptance. In a questionnaire participants were asked to imagine a robot in
      their home and to indicate how much items representing technology, social
      partner, and teammate acceptance matched their robot. There were additional
      questions about how useful and easy to use they thought their robot would be. The
      dependent variables were attitudinal and intentional acceptance. The analysis of
      the responses of 117 older adults (aged 65-86) and 60 younger adults (aged 18-25)
      indicated that individuals thought of robots foremost as performance-directed
      machines, less so as social devices, and least as unproductive entities. The
      robustness of the Technology Acceptance Model to robot acceptance was supported.
      Technology experience accounted for the variance in robot acceptance due to age.

PMID- 25584366
TI  - Genetics of Path Lengths in Brain Connectivity Networks: HARDI-Based Maps in 457
      Adults.
AB  - Brain connectivity analyses are increasingly popular for investigating
      organization. Many connectivity measures including path lengths are generally
      defined as the number of nodes traversed to connect a node in a graph to the
      others. Despite its name, path length is purely topological, and does not take
      into account the physical length of the connections. The distance of the
      trajectory may also be highly relevant, but is typically overlooked in
      connectivity analyses. Here we combined genotyping, anatomical MRI and HARDI to
      understand how our genes influence the cortical connections, using whole-brain
      tractography. We defined a new measure, based on Dijkstra's algorithm, to compute
      path lengths for tracts connecting pairs of cortical regions. We compiled these
      measures into matrices where elements represent the physical distance traveled
      along tracts. We then analyzed a large cohort of healthy twins and show that our
      path length measure is reliable, heritable, and influenced even in young adults
      by the Alzheimer's risk gene, CLU.

PMID- 25584367
TI  - Walter Ricciardi: vision, inspiration and leadership in  European public health.

PMID- 25584368
TI  - Response.

PMID- 25584369
TI  - Response.

PMID- 25584370
TI  - Discussion.

PMID- 25584371
TI  - Toddlers' diabetes: the lost insulin drop and SemiPens vs. DeciPen.
AB  - Background: While childhood diabetes incidence is rising, especially in toddlers,
      once or twice-daily toddler-friendly insulin mixtures were withdrawn, imposing
      four to five miniscule injections, on needle-phobic toddlers. Although more
      injections may mean more needle-dribbling, such potential dose-loss is
      unstudied.Objective: Study insulin loss in toddlers' dose range if one-drop
      dribbled during injection from half-unit pens (SemiPens). Drop-loss is assessed
      relative to current insulin dose adjustment, and if significant, propose
      solutions.Methods: The SemiPens, New HumaPen Luxura HD(r) (HumaPen) and NovoPen
      Junior(r) (NovoPen), with 31G-5mm BD-MicroFine needles were used to study drop
      size or dose-fraction lost if one drop dribbled in dose range 0.5-10
      units.Results: HumaPen and NovoPen produced sizable drops mean standard deviation
      (SD) 0.30 (0.05) and 0.36 (0.06) units/drop (p<0.001). This constituted
      progressively increasing proportion of the toddlers' doses, 10-fold higher
      percentage from 6 to 60% or 7.2 to 72%, as the dose gets smaller from 5 to 0.5
      units.Discussion: Insulin dose-adjustments are usually done therapeutically
      within 5-20% dose-changes, while one-step reduction by >20% is hardly
      required.Therefore, the unintentional dosing change if a drop dribbles is
      clinically important particularly on using multiple doses below 6 units, compared
      with fewer larger daily injections. We propose using U20 insulin in disposable
      SemiPens to make DeciPen, with fivefold-reduction in insulin loss if a drop is
      lost through dribbling or skin-leak.Conclusion: The one-drop insulin loss is
      statistically significant, clinically important, and potentiates glycemic
      variability. Disposable DeciPen may minimize insulin dribbling and leaking and
      fivefold improve dose accuracy and precision; and ensure reproducibility without
      prolonging injection time.

PMID- 25584372
TI  - Seeing in super-resolution.

PMID- 25584373
TI  - The author file: David Kleinfeld.

PMID- 25584374
TI  - Points of significance: two-factor designs.

PMID- 25584375
TI  - The role of LV in the autograft complication after ROSS operation. The authors'
      reply.

PMID- 25584377
TI  - Light microscopy with lattices.

PMID- 25584376
TI  - The yeast two-hybrid assay: still finding connections after 25 years.

PMID- 25584378
TI  - De novo-designed riboregulators.

PMID- 25584379
TI  - Using evolution to predict structure.

PMID- 25584380
TI  - It's porin' CNTs.

PMID- 25584381
TI  - Flies give wings to human disease studies.

PMID- 25584382
TI  - Short reads join hands.

PMID- 25584383
TI  - Unwinding to measure tension.

PMID- 25584384
TI  - Trainee-led research collaboratives: a novel model for delivering  multi-centre
      studies.

PMID- 25584385
TI  - The athleticism of surgery and life: super performing at work and at home...and
      beacons of light.

PMID- 25584386
TI  - Obituary: Prof. Yukio Fukuyama (1928-2014).

PMID- 25584387
TI  - Design, synthesis and structure-activity relationship studies of morpholino-1H
      phenalene derivatives that antagonize Mcl-1/Bcl-2.
AB  - We report herein characteristic studies of Mcl-1 and Bcl-2 dual inhibitors. It
      was found that a protruding carbonyl group forming hydrogen bond with R263 plays
      a predominant role compared with the hydrophobic group that occupies the p2
      pocket. A series of dual inhibitors representing different parts of the
      morpholino-1H-phenalene were designed, synthesized and evaluated.

PMID- 25584388
TI  - Citation for professor Davinder Sandhu for the Award of an 'Honorary Life
      Fellowship' of the British Association of Oral and Maxillfoacial Surgeons.

PMID- 25584389
TI  - Citation for 2013 Down Surgical Prize. Professor Jonathan  Shepherd.

PMID- 25584390
TI  - Citation for professor McCaul for the British Association of Oral and
      Maxillfoacial Surgeons Surgical Prize for 2013.

PMID- 25584391
TI  - Retraction notice to "Degradation of 2,4-dinitroanisole (DNAN) by metabolic
      cooperative activity of Pseudomonas sp. strain FK357 and Rhodococcus imtechensis
      strain RKJ300" [Chemosphere 93 (2013) 2883-8].

PMID- 25584392
TI  - Formation and chlorination of carbazole, phenoxazine, and phenazine.
AB  - This contribution presents pathways for the formation of the three nitrogenated
      dioxin-like species, carbazole, phenoxazine, and phenazine via unimolecular
      rearrangements of diphenylamine (DPA) and its nitro substituents (NDPA). The
      latter represent major structural entities appearing in formulations of
      explosives and propellants. Intramolecular H transfer from the amine group to one
      of the two O atoms in the nitro group denotes the most accessible route in the
      unimolecular decomposition of NDPA. Further unimolecular rearrangements afford
      phenazine and carbazole. A loss of an ortho substituent from DPA, followed by
      addition of an oxygen molecule, prompts the formation of carbazole and
      phenoxazine in a facile mechanism. The consistency between trends in Fukui-based
      electrophilic indices and the experimental profiles of chlorinated carbazole,
      phenoxazine, and phenazine suggests the formation of these species by
      electrophilic substitution. 

PMID- 25584394
TI  - An atom economical method for the direct synthesis of quinoline derivatives from
      substituted o-nitrotoluenes.
AB  - A highly efficient one-pot procedure for the preparation of substituted
      quinolines from substituted o-nitrotoluenes with electron-withdrawing groups and
      olefins (acrylic esters and acrylonitriles) using a cesium catalyst has been
      developed. A plausible [2+4] cycloaddition mechanism is proposed. This method
      uses nitroaromatic compounds as the starting materials to give quinoline
      derivatives in good to high yields under mild conditions with no transition metal
      catalysis. It provides an atom economical pathway for the synthesis of quinoline
      derivatives which could be used in industrial processes. 

PMID- 25584393
TI  - Discovery of potent heterodimeric antagonists of inhibitor of apoptosis proteins
      (IAPs) with sustained antitumor activity.
AB  - The prominent role of IAPs in controlling cell death and their overexpression in
      a variety of cancers has prompted the development of IAP antagonists as potential
      antitumor therapies. We describe the identification of a series of heterodimeric
      antagonists with highly potent antiproliferative activities in cIAP- and XIAP
      dependent cell lines. Compounds 15 and 17 further demonstrate curative efficacy
      in human melanoma and lung cancer xenograft models and are promising candidates
      for advanced studies. 

PMID- 25584396
TI  - Selective binding affinity between quaternary ammonium cations and water-soluble
      calix[4]resorcinarene.
AB  - An amphiphilic calix[4]resorcinarene bearing four hydrophilic sulfonate sites at
      the upper rim and four hydrophobic n-pentyl chains at the lower rim (SR4A5) was
      synthesized by sulfonation of tetramethoxyresorcinarene. The molecular binding
      behaviors of SR4A5 with different types of organic cations, i.e., singly and
      doubly charged aliphatic ammonium salts and singly and doubly charged pi-aromatic
      ammonium salts, were comprehensively investigated by means of (1)H NMR,
      fluorescence, and UV/vis spectroscopic titration experiments. The competitive
      binding titrations demonstrate that, superior to the reported p
      sulfonatocalix[4]arene systems, the stability constants upon association with
      SR4A5 can reach up to 10(6) M(-1) order of magnitude in water, ultimately leading
      to better binding affinity and molecular selectivity toward dicationic guests.
      Significantly, UV/vis spectroscopic experiments further revealed that the
      specific binding behaviors of SR4A5 with bispyridinium guests can be attributed
      to the charge transfer interaction between electron-rich and electron-deficient
      aromatics upon host-guest complexation. These obtained results provide an
      effective strategy to realize the highly selective molecular recognition process
      with multiply charged macrocyclic receptors and will definitely promote the
      development of the field of water-soluble resorcinarene-based supramolecular
      assemblies. 

PMID- 25584395
TI  - Salinipostins A-K, long-chain bicyclic phosphotriesters as a potent and selective
      antimalarial chemotype.
AB  - Despite significant advances in antimalarial chemotherapy over the past 30 years,
      development of resistance to frontline drugs remains a significant challenge that
      limits efforts to eradicate the disease. We now report the discovery of a new
      class of antimalarials, salinipostins A-K, with low nanomolar potencies and high
      selectivity indices against mammalian cells (salinipostin A: Plasmodium
      falciparum EC50 50 nM, HEK293T cytotoxicity EC50 > 50 MUM). These compounds were
      isolated from a marine-derived Salinospora sp. bacterium and contain a bicyclic
      phosphotriester core structure, which is a rare motif among natural products.
      This scaffold differs significantly from the structures of known antimalarial
      compounds and represents a new lead structure for the development of therapeutic
      targets in malaria. Examination of the growth stage specificity of salinipostin A
      indicates that it exhibits growth stage-specific effects that differ from
      compounds that inhibit heme polymerization, while resistance selection
      experiments were unable to identify parasite populations that exhibited
      significant resistance against this compound class. 

PMID- 25584410
TI  - Influence of Crassostrea gigas on the permeability and microstructure of the
      surface layer of concrete exposed to the tidal zone of the Yellow Sea.
AB  - Concrete exposed to the tidal zone of the Yellow Sea and bearing Crassostrea
      gigas (CG) with differing areal coverages was investigated for evidence of
      biologically induced corrosion prevention. The experimental results indicated
      that both the chloride ion profile and the neutralization depth of the concrete
      decreased with increasing CG coverage. Moreover, the water absorption rate and
      the chloride ion permeability of concrete with the original surface intact also
      declined with increasing degrees of CG coverage. However, the water absorption
      rates of three concrete samples with 2 mm of the surface layer removed were
      similar, as was their chloride ion permeability. Mercury intrusion porosimetry
      tests indicated that CG significantly reduced the pore structure of the concrete
      surface layer. SEM observation revealed that the CG cementation membrane and left
      valve were tightly glued to the concrete surface and had a dense structure.
      Concrete durability indices showed that high CG coverage greatly improved
      concrete durability.

PMID- 25584411
TI  - Actions of the small molecule ligands SW106 and AH-3960 on the type-1 parathyroid
      hormone receptor.
AB  - The parathyroid hormone receptor-1 (PTHR1) plays critical roles in regulating
      blood calcium levels and bone metabolism and is thus of interest for small
      molecule ligand development. Of the few small-molecule ligands reported for the
      PTHR1, most are of low affinity, and none has a well-defined mechanism of action.
      Here, we show that SW106 and AH-3960, compounds previously identified to act as
      an antagonist and agonist, respectively, on the PTHR1, each bind to PTHR1-delNT,
      a PTHR1 construct that lacks the large amino-terminal extracellular domain used
      for binding endogenous PTH peptide ligands, with the same micromolar affinity
      with which it binds to the intact PTHR1. SW106 antagonized PTHR1-mediated cAMP
      signaling induced by the peptide analog, M-PTH(1-11), as well as by the native
      PTH(1-9) sequence, as tethered to the extracellular end of transmembrane domain
      (TMD) helix-1 of the receptor. SW106, however, did not function as an inverse
      agonist on either PTHR1-H223R or PTHR1-T410P, which have activating mutations at
      the cytoplasmic ends of TMD helices 2 and 6, respectively. The overall data
      indicate that SW106 and AH-3960 each bind to the PTHR1 TMD region and likely to
      within an extracellularly exposed area that is occupied by the N-terminal
      residues of PTH peptides. Additionally, they suggest that the inhibitory effects
      of SW106 are limited to the extracellular portions of the TMD region that mediate
      interactions with agonist ligands but do not extend to receptor-activation
      determinants situated more deeply in the helical bundle. The study helps to
      elucidate potential mechanisms of small-molecule binding at the PTHR1. 

PMID- 25584413
TI  - Research resource: Monitoring endoplasmic reticulum membrane integrity in beta
      cells at the single-cell level.
AB  - Endoplasmic reticulum (ER) membrane integrity is an emerging target for human
      chronic diseases associated with ER stress. Despite the underlying importance of
      compromised ER membrane integrity in disease states, the entire process leading
      to ER membrane permeabilization and cell death is still not clear due to
      technical limitations. Here we describe a novel method for monitoring ER membrane
      integrity at the single-cell level in real time. Using a beta-cell line
      expressing ER-targeted redox sensitive green fluorescent protein, we could
      identify a beta-cell population undergoing ER membrane permeabilization induced
      by palmitate and could monitor cell fate and ER stress of these cells at the
      single-cell level. Our method could be used to develop a novel therapeutic
      modality targeting the ER membrane for ER-associated disorders, including beta
      cell death in diabetes, neurodegeneration, and Wolfram syndrome. 

PMID- 25584412
TI  - IGFs mediate the action of LH on oocyte maturation in zebrafish.
AB  - LH signaling is required for oocyte maturation in fish and other vertebrates.
      However, the downstream factors mediating LH signaling are largely unexplored in
      fish. In this study, we investigated whether IGFs could mediate LH action on
      oocyte maturation in zebrafish. Our results show that all igfs, including igf1,
      igf2a, igf2b, and igf3, are dynamically expressed during folliculogenesis, with
      the expression of igf3 reaching its maximal level in full grown stage follicles.
      The expression of igfs is regulated by LH through a cAMP pathway in intact
      follicles as well as in primary cultured follicular cells, with igf3 expression
      being the most sensitive to human chorionic gonadotropin (hCG) treatment.
      Moreover, recombinant zebrafish IGF-2a, IGF-2b, and IGF-3 proteins significantly
      enhanced oocyte maturation via IGF-1 receptors (IGF-1rs), with IGF-3 exhibiting
      the most potent stimulatory action on oocyte maturation. Furthermore, we have
      demonstrated that IGF-3 or hCG treatment could stimulate IGF-1rs phosphorylation,
      and hCG-induced oocyte maturation could be attenuated by IGF-1r inhibitors as
      well as by an anti-IGF-3 antiserum in vitro and in vivo, indicating that the IGF
      system especially IGF-3 plays a crucial role in mediating LH action on oocyte
      maturation. In addition, igf3 expression is significantly attenuated in LH beta
      subunit (lhb) mutant zebrafish and treatment with recombinant IGF-3 could
      partially rescue the oocyte maturation defects of the lhb mutants in vitro and in
      vivo. Collectively, our results clearly demonstrated that IGFs, particularly the
      gonad-specific IGF-3, act as important mediators of LH action on oocyte
      maturation in zebrafish. 

PMID- 25584414
TI  - FOXO1 is required for binding of PR on IRF4, novel transcriptional regulator of
      endometrial stromal decidualization.
AB  - The forkhead box O1A (FOXO1) is an early-induced target of the protein kinase A
      pathway during the decidualization of human endometrial stromal cells (HESCs). In
      this study we identified the cistrome and transcriptome of FOXO1 and its role as
      a transcriptional regulator of the progesterone receptor (PR). Direct targets of
      FOXO1 were identified by integrating RNA sequencing with chromatin
      immunoprecipitation followed by deep sequencing. Gene ontology analysis
      demonstrated that FOXO1 regulates a subset of genes in decidualization such as
      those involved in cancer, p53 signaling, focal adhesions, and Wnt signaling. An
      overlap of the FOXO1 and PR chromatin immunoprecipitation followed by deep
      sequencing intervals revealed the co-occupancy of FOXO1 in more than 75% of PR
      binding intervals. Among these intervals were highly enriched motifs for the
      interferon regulatory factor member 4 (IRF4). IRF4 was determined to be a genomic
      target of both FOXO1 and PR and also to be differentially regulated in HESCs
      treated with small interfering RNA targeting FOXO1 or PR prior to decidualization
      stimulus. Ablation of FOXO1 was found to abolish binding of PR to the shared
      binding interval downstream of the IRF4 gene. Finally, small interfering RNA
      mediated ablation of IRF4 was shown to compromise morphological transformation of
      decidualized HESCs and to attenuate the expression of the decidual markers
      IGFBP1, PRL, and WNT4. These results provide the first evidence that FOXO1 is
      functionally required for the binding of PR to genomic targets. Most notably,
      FOXO1 and PR are required for the regulation of IRF4, a novel transcriptional
      regulator of decidualization in HESCs. 

PMID- 25584416
TI  - Comment on "structural determinants of drug partitioning in surrogates of
      phosphatidylcholine bilayer strata".
AB  - The Abraham model correlation for describing the partitioning behavior of solutes
      between water and hexadecane was redetermined using the measured partition
      coefficient data and solute descriptors derived from experimental data. The newly
      derived correlation provides a much better mathematical description of the
      observed partition coefficient data than the correlation given in the published
      paper. 

PMID- 25584417
TI  - Thermally persistent carbonyl nitrene: FC(O)N.
AB  - Transient carbonyl nitrenes RC(O)N, formed during thermal- or photoinduced
      decomposition of carbonyl azides RC(O)N3, are highly liable to the Curtius
      rearrangement, producing isocyanates RNCO in almost quantitative yield. Contrary
      to common belief, we found a thermally persistent triplet carbonyl nitrene,
      FC(O)N, that can be produced by flash pyrolysis of FC(O)N3 in 49% yield. The
      computed CBS-QB3 activation barrier for the thermal decomposition of FC(O)N3 to
      FC(O)N is 29 kJ mol(-1) lower than that for a concerted pathway producing FNCO. 

PMID- 25584418
TI  - Molecular mass and molecular-mass distribution of TEMPO-oxidized celluloses and
      TEMPO-oxidized cellulose nanofibrils.
AB  - Native wood cellulose was oxidized by 2,2,6,6-tetramethylpiperidine-1-oxyl
      (TEMPO)-mediated oxidation, and the fibrous TEMPO-oxidized celluloses (TOCs) thus
      obtained were disintegrated in water to prepare TOC nanofibrils (TOCNs). The
      carboxyl groups of TOCs and TOCNs were methyl-esterified, and the methylated
      samples were dissolved in 8% LiCl/N,N-dimethylacetamide for size-exclusion
      chromatography/multiangle laser-light scattering (SEC-MALLS) analysis to obtain
      their molecular-mass (MM) values and MM distributions (MMDs). The results showed
      that remarkable depolymerization occurred in TOCs and TOCNs and depended on the
      oxidation and sonication conditions. Because single peaks without bimodal
      patterns were observed in the MMDs for all of the TOC and TOCN samples,
      depolymerization may have randomly occurred on whole cellulose molecules and
      oxidized cellulose molecules in the microfibrils during these treatments.
      Compared with the MM values obtained by SEC-MALLS, the intrinsic viscosities of
      TOCs dissolved in 0.5 M copper ethylenediamine solution provided lower MM values
      owing to depolymerization during the dissolution and postreduction processes. 

PMID- 25584415
TI  - Serine-727 phosphorylation activates hypothalamic STAT-3 independently from
      tyrosine-705 phosphorylation.
AB  - Transcriptional activity of signal transducer and activator of transcription-3
      (STAT-3) is a key element in the central regulation of appetite and energy
      homeostasis. Activation of hypothalamic STAT-3 has been attributed to cytokine
      promoted phosphorylation at tyrosine-705 (Tyr-705). In nonhypothalamic cells,
      STAT-3 is also phosphorylated at serine-727 (Ser-727), but the functional
      significance of Ser-727 in the regulation of hypothalamic STAT-3 is not known. We
      used 2 hypothalamic cell lines and analyzed the effects of various hormones on
      STAT-3-dependent reporter gene activity and observed that IFN-gamma, epidermal
      growth factor (EGF), and bradykinin (BK) induce similar STAT-3 reporter
      activation. EGF and BK solely increased Ser-727 and IFN-gamma increased Tyr-705
      phosphorylation of STAT-3. Specific inhibition of ERK-1/2 activity blocked EGF-
      and BK-induced STAT-3 activation and Ser-727 phosphorylation. BK-induced ERK-1/2
      activation occurred via EGF receptor transactivation. Consequently, the BK
      mediated effects on STAT-3 were blocked by a specific EGF receptor antagonist.
      Next, we analyzed the effects of IFN-gamma and EGF on the expression of the STAT
      3-dependent genes thyroliberin-releasing hormone and suppressors of cytokine
      signaling-3. EGF but not IFN-gamma enhanced thyroliberin-releasing hormone
      expression via STAT-3. With regard to suppressors of cytokine signaling-3, we
      observed prolonged expression induced by IFN-gamma and a transient effect of EGF
      that required coactivation of the activator protein-1. Thus, EGF-promoted Ser-727
      phosphorylation by ERK-1/2 is not only sufficient to fully activate hypothalamic
      STAT-3, but, in terms of targeted genes and required cofactors, entails distinct
      modes of STAT-3 actions compared with IFN-gamma-induced Tyr-705 phosphorylation. 

PMID- 25584419
TI  - The effect of smoke-free air law in bars on smoking initiation and relapse among
      teenagers and young adults.
AB  - BACKGROUND: Existing evidence has shown that most smoking uptake and escalation
      occurs while smokers are teenagers or young adults. Effective policies that
      reduce smoking uptake and escalation will play an important role in curbing
      cigarette smoking. This study aims to investigate the effect of smoke-free air
      (SFA) laws in bars on smoking initiation/relapse while controlling for other
      confounders. METHODS: The national longitudinal Survey of Youth 1997 (NLSY97)
      from 1997-2009 was linked to state-level scores for the strength of SFA laws in
      order to carry out the analysis. RESULTS AND CONCLUSION: We find that SFA laws in
      bars with exemptions significantly reduce (p <= 0.01) the probability of smoking
      initiation (one-puff, daily, and heavy smoking initiation). The 100% SFA law in
      bars without exemption significantly deters smoking relapse from abstinence into
      daily smoking (p <= 0.05) or relapse from abstinence into heavy smoking (p <=
      0.01) among people age 21 or older. The reduction of one-puff and daily smoking
      initiation is larger among ages 20 or younger than ages 21 or older, while the
      reduction in relapse does not differ by whether respondents reach the drinking
      age. Results also indicate that higher cigarette taxes significantly reduce daily
      smoking initiation and relapse into nondaily and light smoking.

PMID- 25584420
TI  - Assessment of Malawian mothers' malaria knowledge, healthcare preferences and
      timeliness of seeking fever treatments for children under five.
AB  - Malaria is one of the major public health problems in Malawi, contributing to the
      majority of morbidity and mortality among children under five. Ignorance of
      malaria symptoms results in delayed treatment, which often degenerates into fatal
      emergencies. This study analyzed the impact of maternal malaria knowledge on
      healthcare preferences and timeliness of treating children with reported fever.
      The Malaria Indicator Survey data for 2012, which were adequately weighted, were
      analyzed using multinomial logit and Poisson regression models. The results
      showed low maternal average years of formal education (3.52) and average mothers'
      age was 27.97 years. Majority of the women (84.98%) associated fever with
      malaria, while 44.17% associated it with chilling. Also, 54.42% and 32.43% of the
      children were treated for fever on the same day and the following day that fever
      started, respectively. About 9.70% paid for fever treatment from their regular
      incomes, while 51.38% sought treatment from either public or private health
      centers. Multinomial Logit regression results showed that relative to using of
      other treatments, probabilities of selecting private hospitals and public health
      centers increased with age of the household heads, resident in urban areas,
      mothers' years of education, number of days taken off for treatment, paying
      medical bills from regular, occasional and borrowed incomes, and knowledge of
      diarrhea and shivering as symptoms of malaria. In the Poisson regression results,
      timeliness of seeking treatment was significantly enhanced by knowledge of fever
      as malaria symptom, residence in northern and central regions of Malawi and use
      of income from sale of assets to pay medical bills (p < 0.10).However, delays in
      treating children was motivated by age of the household heads, number of days
      taken off to care for sick child and usage of regular, borrowed and other incomes
      to pay medical bills. (p < 0.05). It was concluded that efficiency of public
      sector in treating malaria holds significant prospects for fighting malaria in
      Malawi. However, adequate efforts should be channeled in enhancing the knowledge
      of women on malaria symptoms, among others. 

PMID- 25584421
TI  - Managing an online survey about influenza vaccination in primary healthcare
      workers.
AB  - Online surveys are increasingly used due to their speed and efficiency. The aim
      of this study was to analyze factors that may have contributed to the quality and
      speed of response of an online survey on influenza vaccination in primary
      healthcare workers. A multicenter study including family physicians, nurses and
      pediatricians from primary healthcare teams from seven Spanish Autonomous
      Communities was designed. The centers were selected by simple random sampling.
      The survey remained active and accessible for 56 days and four reminders were
      sent. The odds ratios (OR) and their 95% confidence intervals (CI) were
      calculated to assess the association of sociodemographic variables and responding
      to the survey before the second reminder. Complete, validated information was
      obtained from 1965 primary healthcare workers. The total response rate was 36.2%.
      More nurses (46.3%) responded before the second reminder and more family
      physicians (52.8%) after the second reminder. The adjusted OR shows that family
      physicians responded later (AOR 1.46, 95% CI 1.2-1.8) than nurses. The responses
      obtained in the first 24 h after the initial sending and the reminders accounted
      for 41.7% of the completed surveys, indicating the importance of reminders. 

PMID- 25584422
TI  - Prevalence of diabetes mellitus and impaired fasting glucose, associated with
      risk factors in rural Kazakh adults in Xinjiang, China.
AB  - OBJECTIVE: This study aimed to estimate the prevalence of diabetes mellitus (DM)
      and impaired fasting glucose (IFG) in a Kazakh population aged >=18 years living
      in the YiLi District of Xinjiang, China and to evaluate the associated risk
      factors of diabetes. METHODS: Randomly selected adults, living for at least 6
      months in the YiLi District in Xinjiang had their clinical characteristics and
      standard blood chemistries measured. DM and IFG were defined according to WHO
      1999 criteria. The adjusted odds ratio (ORs) and 95% confidence intervals were
      calculated for the association of diabetes risk factors in multivariate logistic
      regression models. RESULTS: A total of 3919 subjects were randomly selected. The
      age-and gender-standardized prevalence of DM and IFG were 5.9% and 10.0%,
      respectively. The prevalence of DM and IFG increased with age and BMI. Prevalence
      of 7.4%, 12.2% in males and 4.9%, 8.6% in females for DM and IFG. Compared by
      sex, prevalence of DM and IFG was higher in males. Prevalence of 3.4%, 8.1% in
      normal, 6.7%, 11.9% in overweight and 12.0%, 13.0% in obesity for diabetes and
      IFG. In the multivariable logistic models, male sex, older age, unmarried,
      overweight, obesity, hypertension, triglycerides and smoking were all
      significantly associated with an increased risk of diabetes. CONCLUSIONS: The
      prevalence of DM and IFG among minorities was lower than the overall national
      level both in men and women (9.7% in total, 10.6% in males, 8.8% in females), and
      also lower than among the Han ethnicity (9.26%) which predominates in China
      today.

PMID- 25584424
TI  - The nature of the global effect beyond the first eye movement.
AB  - When two or more visual objects appear in close proximity, the initial oculomotor
      response is systematically aimed at a location in between the objects, a
      phenomenon named the global effect. The global effect is known to arise when
      saccades are initiated relatively quickly, immediately after the presentation of
      a display, but it has also been shown that a global effect may occur much later
      in time, even for eye movements beyond the first. That is, when participants are
      searching for a complex target among complex distractor objects, it can take
      several eye movements to hit the target, and these eye movements mainly land at
      intermediate locations. It is debatable whether these findings are caused by the
      same mechanisms as those involved in the more typical global effect studies,
      studies in which much simpler search tasks are employed. In the current two
      experiments, we examined whether and under which circumstances a global effect
      can be found for a second oculomotor response in a search display containing two
      simple objects. Experiment 1 showed that the global effect only occurs when the
      presentation of the target and distractor objects is delayed, until after the
      first oculomotor response is initiated. Experiment 2 demonstrated that identity
      information, rather than spatial information, is crucial for the occurrence of
      the global effect. These results suggest that the global effect is not due to a
      failure to dissociate between the locations of multiple objects, but a failure to
      determine which one is the target. 

PMID- 25584423
TI  - Diet and physical activity interventions to prevent or treat obesity in South
      Asian children and adults: a systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: The metabolic risks associated with obesity are greater for
      South Asian populations compared with White or other ethnic groups, and levels of
      obesity in childhood are known to track into adulthood. Tackling obesity in South
      Asians is therefore a high priority. The rationale for this systematic review is
      the suggestion that there may be differential effectiveness in diet and physical
      activity interventions in South Asian populations compared with other
      ethnicities. The research territory of the present review is an emergent, rather
      than mature, field of enquiry, but is urgently needed. Thus the aim of this
      systematic review and meta-analysis was to assess the effectiveness of diet and
      physical activity interventions to prevent or treat obesity in South Asians
      living in or outside of South Asia and to describe the characteristics of
      effective interventions. METHODS: Systematic review of any type of lifestyle
      intervention, of any length of follow-up that reported any anthropometric measure
      for children or adults of South Asian ethnicity. There was no restriction on the
      type of comparator; randomised controlled trials, controlled clinical trials, and
      before-after studies were included. A comprehensive search strategy was
      implemented in five electronic databases: ASSIA, Cochrane Controlled Trials
      Register, Embase, Medline and Social Sciences Citation Index. The search was
      limited to English language abstracts published between January 2006 and January
      2014. References were screened; data extraction and quality assessment were
      carried out by two reviewers. RESULTS are presented in narrative synthesis and
      meta-analysis. RESULTS: Twenty-nine studies were included, seven children, 21
      adult and one mixed age. No studies in children under six were identified.
      Sixteen studies were conducted in South Asia, ten in Europe and three in USA.
      Effective or promising trials include physical activity interventions in South
      Asian men in Norway and South Asian school-children in the UK. A home-based,
      family-orientated diet and physical activity intervention improved obesity
      outcomes in South Asian adults in the UK, when adjusted for baseline differences.
      Meta-analyses of interventions in children showed no significant difference
      between intervention and control for body mass index or waist circumference. Meta
      analyses of adult interventions showed significant improvement in weight in data
      from two trials adjusted for baseline differences (mean difference -1.82 kgs, 95%
      confidence interval -2.48 to -1.16) and in unadjusted data from three trials
      following sensitivity analysis (mean difference -1.20 kgs, 95% confidence
      interval -2.23 to -0.17). Meta-analyses showed no significant differences in body
      mass index and waist circumference for adults. Twenty of 24 intervention groups
      showed improvements in adult body mass index from baseline to follow-up; average
      change in high quality studies (n = 7) ranged from 0.31 to -0.8 kg/m2. There was
      no evidence that interventions were more or less effective according to whether
      the intervention was set in South Asia or not, or by socio-economic status.
      CONCLUSIONS: Meta-analysis of a limited number of controlled trials found an
      unclear picture of the effects of interventions on body mass index for South
      Asian children. Meta-analyses of a limited number of controlled trials showed
      significant improvement in weight for adults but no significant differences in
      body mass index and waist circumference. One high quality study in South Asian
      children found that a school-based physical activity intervention that was
      delivered within the normal school day which was culturally sensitive, was
      effective. There is also evidence of culturally appropriate approaches to, and
      characteristics of, effective interventions in adults which we believe could be
      transferred and used to develop effective interventions in children.

PMID- 25584425
TI  - Requiem for the max rule?
AB  - In tasks such as visual search and change detection, a key question is how
      observers integrate noisy measurements from multiple locations to make a
      decision. Decision rules proposed to model this process have fallen into two
      categories: Bayes-optimal (ideal observer) rules and ad-hoc rules. Among the
      latter, the maximum-of-outputs (max) rule has been the most prominent. Reviewing
      recent work and performing new model comparisons across a range of paradigms, we
      find that in all cases except for one, the optimal rule describes human data as
      well as or better than every max rule either previously proposed or newly
      introduced here. This casts doubt on the utility of the max rule for
      understanding perceptual decision-making. 

PMID- 25584426
TI  - Formation of 3D cholesterol crystals from 2D nucleation sites in lipid bilayer
      membranes: implications for atherosclerosis.
AB  - Atherosclerosis is the major precursor of cardiovascular disease. The formation
      of cholesterol crystals in atherosclerotic plaques is associated with the onset
      of acute pathology. The cholesterol crystals induce physical injury in the plaque
      core, promoting cell apoptosis and triggering an increased inflammatory response.
      Herein we address the question of how cholesterol crystal formation occurs in
      atherosclerosis. We demonstrate that three-dimensional (3D) cholesterol crystals
      can undergo directed nucleation from bilayer membranes containing two-dimensional
      (2D) cholesterol crystalline domains. We studied crystal formation on supported
      lipid bilayers loaded with exogenous cholesterol and labeled using a monoclonal
      antibody that specifically recognizes ordered cholesterol arrays. Our findings
      show that 3D crystals are formed exclusively on the bilayer regions where there
      are segregated 2D cholesterol crystalline domains and that they form on the
      domains. This study has potentially significant implications for our
      understanding of the crucial step in the mechanism by which atherosclerotic
      lesions form. 

PMID- 25584428
TI  - effects of natural flavonoids on photosynthetic activity and cell integrity in
      Microcystis aeruginosa.
AB  - Flavonoids are natural polyphenolic compounds produced by many aquatic plants and
      released in their environments. In this study, the effects of several aquatic
      flavonoids on cyanobacterial Microcystis aeruginosa, especially in relation to
      the cell growth, photosynthetic activity, cell morphology, and cell membrane
      integrity, were investigated. Significant growth inhibition was observed when the
      cyanobacteria were exposed to three flavonoids, namely, 5,4'-dihydroxyflavone
      (DHF), apigenin, and luteolin. Luteolin reduced the effective quantum yield,
      photosynthetic efficiency, and maximal electron transport rate by 70%, 59% and
      44%, respectively, whereas 5,4'-DHF and apigenin slightly affected these
      parameters, which implies that luteolin disrupts the photosynthetic system.
      Moreover, 5,4'-DHF and apigenin compromised the membrane integrity, and induced
      membrane depolarization in 52% and 38%, and permeabilization in 30% and 44% of
      the cells, respectively. The 5,4'-DHF and apigenin showed more pronounced effects
      on M. aeruginosa morphology and membrane integrity, compared to the luteolin.
      These results suggest that flavonoids could have significant effects on growth
      and physiological functions in cyanobacterial species. 

PMID- 25584427
TI  - Ricin trafficking in cells.
AB  - The heterodimeric plant toxin ricin binds exposed galactosyls at the cell surface
      of target mammalian cells, and, following endocytosis, is transported in
      vesicular carriers to the endoplasmic reticulum (ER). Subsequently, the cell
      binding B chain (RTB) and the catalytic A chain (RTA) are separated reductively,
      RTA embeds in the ER membrane and then retrotranslocates (or dislocates) across
      this membrane. The protein conducting channels used by RTA are usually regarded
      as part of the ER-associated protein degradation system (ERAD) that removes
      misfolded proteins from the ER for destruction by the cytosolic proteasomes.
      However, unlike ERAD substrates, cytosolic RTA avoids destruction and folds into
      a catalytic conformation that inactivates its target ribosomes. Protein synthesis
      ceases, and subsequently the cells die apoptotically. This raises questions about
      how this protein avoids the pathways that are normally sanctioned for ER
      dislocating substrates. In this review we focus on the molecular events that
      occur with non-tagged ricin and its isolated subunits at the ER-cytosol
      interface. This focus reveals that intra-membrane interactions of RTA may control
      its fate, an area that warrants further investigation. 

PMID- 25584429
TI  - Triggering apoptotic death of human epidermal keratinocytes by malic Acid:
      involvement of endoplasmic reticulum stress- and mitochondria-dependent signaling
      pathways.
AB  - Malic acid (MA) has been commonly used in cosmetic products, but the safety
      reports in skin are sparse. To investigate the biological effects of MA in human
      skin keratinocytes, we investigated the potential cytotoxicity and apoptotic
      effects of MA in human keratinocyte cell lines (HaCaT). The data showed that MA
      induced apoptosis based on the observations of DAPI staining, DNA fragmentation,
      and sub-G1 phase in HaCaT cells and normal human epidermal keratinocytes (NHEKs).
      Flow cytometric assays also showed that MA increased the production of
      mitochondrial superoxide (mito-SOX) but decreased the mitochondrial membrane
      potential. Analysis of bioenergetics function with the XF 24 analyzer Seahorse
      extracellular flux analyzer demonstrated that oxygen consumption rate (OCR) was
      significantly decreased whereas extracellular acidification rate (ECAR) was
      increased in MA-treated keratinocytes. The occurrence of apoptosis was proved by
      the increased expressions of FasL, Fas, Bax, Bid, caspases-3, -8, -9, cytochrome
      c, and the declined expressions of Bcl-2, PARP. MA also induced endoplasmic
      reticulum stress associated protein expression such as GRP78, GADD153, and
      ATF6alpha. We demonstrated that MA had anti-proliferative effect in HaCaT cell
      through the inhibition of cell cycle progression at G0/G1, and the induction of
      programmed cell death through endoplasmic reticulum stress- and mitochondria
      dependent pathways. 

PMID- 25584430
TI  - Acceptance: what's in a name? A content analysis of acceptance instruments in
      individuals with chronic pain.
AB  - Instruments to assess chronic pain acceptance have been developed and used.
      However, whether and to what extent the content of the items reflects acceptance
      remain uninvestigated. A content analysis of 13 instruments that aim to measure
      acceptance of chronic pain was performed. A coding scheme was used that consisted
      of 3 categories representing the key components of acceptance, that is,
      disengagement from pain control, pain willingness, and engagement in activities
      other than pain control. The coding scheme consisted of 5 additional categories
      in order to code items that do not represent acceptance, that is, controlling
      pain, pain costs, pain benefits, unclear, and no fit. Two coders rated to what
      extent the items of acceptance instruments belonged to one or more of these
      categories. Results indicated that acceptance categories were not equally
      represented in the acceptance instruments. Of note, some instruments had many
      items in the category controlling pain. Further analyses revealed that the
      meaning of acceptance differs among different instruments and among different
      versions of the same instrument. This study illustrates the importance of content
      validity when developing and evaluating self-report instruments. PERSPECTIVE:
      This article investigated the content validity of questionnaires designed to
      measure acceptance in individuals with chronic pain. Knowledge about the content
      of the instruments will provide further insight into the features of acceptance
      and how to measure them.

PMID- 25584431
TI  - Randomized intubation with polyurethane or conical cuffs to prevent pneumonia in
      ventilated patients.
AB  - RATIONALE: The occurrence of ventilator-associated pneumonia (VAP) is linked to
      the aspiration of contaminated pharyngeal secretions around the endotracheal
      tube. Tubes with cuffs made of polyurethane rather than polyvinyl chloride or
      with a conical rather than a cylindrical shape increase tracheal sealing.
      OBJECTIVES: To test whether using polyurethane and/or conical cuffs reduces
      tracheal colonization and VAP in patients with acute respiratory failure.
      METHODS: We conducted a multicenter, prospective, open-label, randomized study in
      four parallel groups in four intensive care units between 2010 and 2012. A cohort
      of 621 patients with expected ventilation longer than 2 days was included at
      intubation with a cuff composed of cylindrical polyvinyl chloride (n = 148),
      cylindrical polyurethane (n = 143), conical polyvinyl chloride (n = 150), or
      conical polyurethane (n = 162). We used Kaplan-Meier estimates and log-rank tests
      to compare times to events. MEASUREMENTS AND MAIN RESULTS: After excluding 17
      patients who secondarily refused participation or had met an exclusion criterion,
      604 were included in the intention-to-treat analysis. Cumulative tracheal
      colonization greater than 10(3) cfu/ml at Day 2 was as follows (median
      [interquartile range]): cylindrical polyvinyl chloride, 0.66 (0.58-0.74);
      cylindrical polyurethane, 0.61 (0.53-0.70); conical polyvinyl chloride, 0.67
      (0.60-0.76); and conical polyurethane, 0.62 (0.55-0.70) (P = 0.55). VAP developed
      in 77 patients (14.4%), and postextubational stridor developed in 28 patients
      (6.4%) (P = 0.20 and 0.28 between groups, respectively). CONCLUSIONS: Among
      patients requiring mechanical ventilation, polyurethane and/or conically shaped
      cuffs were not superior to conventional cuffs in preventing tracheal colonization
      and VAP. Clinical trial registered with clinicaltrials.gov (NCT01114022).

PMID- 25584432
TI  - Differential metabolic responses of Beauveria bassiana cultured in pupae
      extracts, root exudates and its interactions with insect and plant.
AB  - Beauveria bassiana is a kind of world-wide entomopathogenic fungus and can also
      colonize plant rhizosphere. Previous researches showed differential expression of
      genes when entomopathogenic fungi are cultured in insect or plant materials.
      However, so far there is no report on metabolic alterations of B. bassiana in the
      environments of insect or plant. The purpose of this paper is to address this
      problem. Herein, we first provide the metabolomic analysis of B. bassiana
      cultured in insect pupae extracts (derived from Euproctis pseudoconspersa and
      Bombyx mori, EPP and BMP), plant root exudates (derived from asparagus and
      carrot, ARE and CRE), distilled water and minimal media (MM), respectively.
      Principal components analysis (PCA) shows that mycelia cultured in pupae extracts
      and root exudates are evidently separated and individually separated from MM,
      which indicates that fungus accommodates to insect and plant environments by
      different metabolic regulation mechanisms. Subsequently, orthogonal projection on
      latent structure-discriminant analysis (OPLS-DA) identifies differential
      metabolites in fungus under three environments relative to MM. Hierarchical
      clustering analysis (HCA) is performed to cluster compounds based on biochemical
      relationships, showing that sphingolipids are increased in BMP but are decreased
      in EPP. This observation further implies that sphingolipid metabolism may be
      involved in the adaptation of fungus to different hosts. In the meantime,
      sphingolipids are significantly decreased in root exudates but they are not
      decreased in distilled water, suggesting that some components of the root
      exudates can suppress sphingolipid to down-regulate sphingolipid metabolism.
      Pathway analysis finds that fatty acid metabolism is maintained at high level but
      non-ribosomal peptides (NRP) synthesis is unaffected in mycelia cultured in pupae
      extracts. In contrast, fatty acid metabolism is not changed but NRP synthesis is
      high in mycelia cultured in root exudates and distilled water. This indicates
      that fungal fatty acid metabolism is enhanced when contacting insect, but when in
      the absence of insect hosts NRP synthesis is increased. Ornithine, arginine and
      GABA are decreased in mycelia cultured in pupae extracts and root exudates but
      remain unchanged in distilled water, which suggests that they may be associated
      with fungal cross-talk with insects and plants. Trehalose and mannitol are
      decreased while adenine is increased in three conditions, signifying carbon
      shortage in cells. Together, these results unveil that B. bassiana has
      differential metabolic responses in pupae extracts and root exudates, and
      metabolic similarity in root exudates and distilled water is possibly due to the
      lack of insect components. 

PMID- 25584433
TI  - Nanovectorization of TRAIL with single wall carbon nanotubes enhances tumor cell
      killing.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a
      member of the tumor necrosis factor (TNF) superfamily. This type II transmembrane
      protein is able to bound specifically to cancer cell receptors (i.e., TRAIL-R1
      (or DR4) and TRAIL-R2 (or DR5)) and to induce apoptosis without being toxic for
      healthy cells. Because membrane-bound TRAIL induces stronger receptor aggregation
      and apoptosis than soluble TRAIL, we proposed here to vectorize TRAIL using
      single-walled carbon nanotubes (SWCNTs) to mimic membrane TRAIL. Owing to their
      exceptional and revolutional properties, carbon nanotubes, especially SWCNTs, are
      used in a wide range of physical or, now, medical applications. Indeed due to
      their high mechanical resistance, their high flexibility and their
      hydrophobicity, SWCNTs are known to rapidly diffuse in an aqueous medium such as
      blood, opening the way of development of new drug nanovectors (or nanocarriers).
      Our TRAIL-based SWCNTs nanovectors proved to be more efficient than TRAIL alone
      death receptors in triggering cancer cell killing. These NPTs increased TRAIL pro
      apoptotic potential by nearly 20-fold in different Human tumor cell lines
      including colorectal, nonsmall cell lung cancer, or hepatocarcinomas. We provide
      thus a proof-of-concept that TRAIL nanovector derivatives based on SWCNT may be
      useful to future nanomedicine therapies. 

PMID- 25584434
TI  - Kinetically stabilized aliovalent europium-doped magnesium oxide as a UV
      sensitized phosphor.
AB  - Doping of size mismatched aliovalent ions is challenging due to the associated
      elastic and electronic stress making the thermodynamics unfavorable. Despite such
      features, its utilization may be viable if such systems can be made metastable by
      suppressing the kinetics of phase segregation. In light of such a possibility, we
      utilize sol-gel synthesis for preparing a size mismatched trivalent europium
      doped MgO (Mg(1-x)Eu(x)O:(x/2)V"(Mg)) system, which can be potentially used in
      optical applications. It is found that such a doped system can be metastabilized
      and the extent of metastability can be correlated with critical temperature (Tc)
      required for phase segregation which decreases with the dopant concentration. For
      x = 0.005, 0.01, and 0.02, Tc is above 1200  degrees C, 500-800  degrees C and
      less than 500  degrees C, respectively. As the synthesis temperature is 500 
      degrees C, these trends in critical temperatures make it impossible to
      metastabilize europium in MgO with x > 0.01. Doping is evident from X-ray
      diffraction data, excitation spectra, high resolution emission spectra, and
      luminescence lifetimes. A characteristic strong red emission of Eu(3+) has been
      observed via energy transfer from the MgO matrix to Eu(3+). Density functional
      theory based simulations suggest stabilization of Eu(3+) in MgO at lower doping
      concentration through the formation of cation vacancies which is also evident
      from optical studies. Furthermore, thin films deposited using the e-beam
      evaporation technique from the Mg(1-x)Eu(x)O:(x/2)V"(Mg) (x = 0.005) system show
      UV sensitized emission with CIE coordinates (0.26, 0.21).

PMID- 25584435
TI  - Identification of ice nucleation active sites on feldspar dust particles.
AB  - Mineral dusts originating from Earth's crust are known to be important
      atmospheric ice nuclei. In agreement with earlier studies, feldspar was found as
      the most active of the tested natural mineral dusts. Here we investigated in
      closer detail the reasons for its activity and the difference in the activity of
      the different feldspars. Conclusions are drawn from scanning electron microscopy,
      X-ray powder diffraction, infrared spectroscopy, and oil-immersion freezing
      experiments. K-feldspar showed by far the highest ice nucleation activity.
      Finally, we give a potential explanation of this effect, finding alkali-metal
      ions having different hydration shells and thus an influence on the ice
      nucleation activity of feldspar surfaces. 

PMID- 25584436
TI  - Competitive evaluation of data mining algorithms for use in classification of
      leukocyte subtypes with Raman microspectroscopy.
AB  - Raman microspectroscopy has been investigated for some time for use in label-free
      cell sorting devices. These approaches require coupling of the Raman spectrometer
      to complex data mining algorithms for identification of cellular subtypes such as
      the leukocyte subpopulations of lymphocytes and monocytes. In this study, three
      distinct multivariate classification approaches, (PCA-LDA, SVMs and Random
      Forests) are developed and tested on their ability to classify the cellular
      subtype in extracted peripheral blood mononuclear cells (T-cell lymphocytes from
      myeloid cells), and are evaluated in terms of their respective classification
      performance. A strategy for optimisation of each of the classification algorithm
      is presented with emphasis on reduction of model complexity in each of the
      algorithms. The relative classification performance and performance
      characteristics are highlighted, overall suggesting the radial basis function SVM
      as a robust option for classification of leukocytes with Raman microspectroscopy.

PMID- 25584437
TI  - The combination of two novel tobacco blends and filter technologies to reduce the
      in vitro genotoxicity and cytotoxicity of prototype cigarettes.
AB  - Tobacco smoke from a combustible cigarette contains more than 6000 constituents;
      approximately 150 of these are identified as toxicants. Technologies that modify
      the tobacco blend to reduce toxicant emissions have been developed. These include
      tobacco sheet substitute to dilute toxicants in smoke and blend treated tobacco
      to reduce the levels of nitrogenous precursors and some polyphenols. Filter
      additives to reduce gas (vapour) phase constituents have also been developed. In
      this study, both tobacco blend and filter technologies were combined into an
      experimental cigarette and smoked to International Organisation on
      Standardisation and Health Canada puffing parameters. The resulting particulate
      matter was subjected to a battery of in vitro genotoxicity and cytotoxicity
      assays - the Ames test, mouse lymphoma assay, the in vitro micronucleus test and
      the Neutral Red Uptake assay. The results indicate that cigarettes containing
      toxicant reducing technologies may be developed without observing new additional
      genotoxic hazards as assessed by the assays specified. In addition, reductions in
      bacterial mutagenicity and mammalian genotoxicity of the experimental cigarette
      were observed relative to the control cigarettes. There were no significant
      differences in cytotoxicity relative to the control cigarettes. 

PMID- 25584440
TI  - Mitral valve replacement in patients under 65 years of age: mechanical or
      biological valves?
AB  - PURPOSE OF REVIEW: There is controversy regarding the optimal choice of
      prosthetic valves in patients less than 65 years of age requiring mitral valve
      replacement (MVR). Recently, trends for valve replacement are moving towards
      biological prosthesis also in younger patients, which is justified by the fact
      that a later valve-in-valve procedure is feasible in the case of degeneration of
      the tissue valve. This strategy is increasingly recommended in aortic valve
      surgery but is questionable for MVR. The purpose of this review is to evaluate
      current guidelines and analyse evidence for biological MVR in patients under 65
      years. RECENT FINDINGS: There are differences between guidelines of the American
      Heart Association and those of the European Society of Cardiology concerning the
      choice of prostheses in patients undergoing MVR. Although the European Society of
      Cardiology recommends a mechanical mitral valve in patients under 65 years of
      age, the American Heart Association does not provide detailed advice for these
      patients. Mitral valve replacement with biological valves in patients under 65
      years is associated with higher rates of reoperation due to structural valve
      deterioration. In addition, several studies showed a decreased survival after
      biological MVR. SUMMARY: Evidence for biological MVR in patients less than 65
      years without comorbidities or contraindication for oral anticoagulation does not
      exist. Recommendations for patients less than 65 years of age should not be
      blurred by current 'en-vogue' methods for promising but not yet proven valve-in
      valve strategies.

PMID- 25584438
TI  - Utilizing relative potency factors (RPF) and threshold of toxicological concern
      (TTC) concepts to assess hazard and human risk assessment profiles of
      environmental metabolites: a case study.
AB  - There is currently no standard paradigm for hazard and human risk assessment of
      environmental metabolites for agrochemicals. Using an actual case study,
      solutions to challenges faced are described and used to propose a generic concept
      to address risk posed by metabolites to human safety. A novel approach - built on
      the foundation of predicted human exposures to metabolites in various
      compartments (such as food and water), the threshold of toxicological concern
      (TTC) and the concept of comparative toxicity - was developed for environmental
      metabolites of a new chemical, sulfoxaflor (X11422208). The ultimate aim was to
      address the human safety of the metabolites with the minimum number of in vivo
      studies, while at the same time, ensuring that human safety would be considered
      addressed on a global regulatory scale. The third component, comparative
      toxicity, was primarily designed to determine whether the metabolites had the
      same or similar toxicity profiles to their parent molecule, and also to one
      another. The ultimate goal was to establish whether the metabolites had the
      potential to cause key effects - such as cancer and developmental toxicity, based
      on mode-of-action (MoA) studies - and to develop a relative potency factor (RPF)
      compared to the parent molecule. Collectively, the work presented here describes
      the toxicology programme developed for sulfoxaflor and its metabolites, and how
      it might be used to address similar future challenges aimed at determining the
      relevance of the metabolites from a human hazard and risk perspective.
      Sulfoxaflor produced eight environmental metabolites at varying concentrations in
      various compartments - soil, water, crops and livestock. The MoA for the primary
      effects of the parent molecule were elucidated in detail and a series of in
      silico, in vitro, and/or in vivo experiments were conducted on the environmental
      metabolites to assess relative potency of their toxicity profiles when compared
      to the parent. The primary metabolite, X11719474 found in soil, crops and,
      potentially, at low concentrations, in groundwater, was the most extensively
      studied, with genetic, acute, short-term rat and dog, rodent reproductive and
      developmental toxicity studies, and MoA studies conducted. These data supported
      that the toxicity profile for X11719474 was limited to liver effects via the same
      MoA as the parent and, overall, X11719474 was significantly less toxic than
      parent. Subsequently, the comparative toxicology programme was extended to cover
      all metabolites of sulfoxaflor. Based on structure (i.e., similarity of
      metabolite structures to one another), toxic effects in comparison with parent
      (i.e., consistency of the toxicity profiles and confidence in terms of ability to
      read across), residue compartment (e.g., crop, soil, water) and predicted level
      of exposure, fewer studies were required for establishing safety of these
      metabolites compared to X11719474. For example, for some metabolites with very
      low predicted environmental concentrations only genotoxicity testing was
      required. For some metabolites with low predicted concentrations, for example
      only present in liver, a TTC approach was utilized. This strategy of comparative
      assessment utilizing MoA data, relative potency, hazard characterization, read
      across, predicted exposure and TTC provided a robust database, which minimized
      animal use, comprehensively assessed the hazard and human risk presented by these
      metabolites. 

PMID- 25584441
TI  - Practice with persons with autism spectrum disorders: predictors of self-efficacy
      among social work students.
AB  - Diagnoses of autism spectrum disorders (ASDs) have been on the rise, and the need
      for knowledgeable and competent professionals is dire. However, few social
      workers enter the field of ASDs. Rooted in social cognitive theory, this study
      examined the extent to which knowledge, interest, contact, and training predicted
      master's in social work students' self-efficacy in working with individuals with
      ASDs. Approximately 18% of the variance was explained (R(2) = .18, p < .001),
      with knowledge and contact predicting a significant proportion of the variance.
      Implications for social work practice and education are discussed. 

PMID- 25584442
TI  - Development and evaluation of a stand-alone index for the assessment of small
      children's diet quality.
AB  - OBJECTIVE: To construct and evaluate an independent Children's Index of Diet
      Quality (CIDQ). DESIGN: A food consumption questionnaire, which contained twenty
      five multiple-item questions on eating and food intake, was formulated and
      evaluated against 7 d food records. Key questions that best reflected a healthy
      diet, defined in criteria set by the nutrient recommendations, were searched and
      validated by correlation and analyses of receiver-operating characteristic
      curves. Settings A cohort of a young population of South-West Finland. SUBJECTS:
      Participants (n 400) were 2-6-year-old children. RESULTS: Fifteen questions were
      identified to best depict the children's diet quality in reference to the
      recommendations. These questions were scored, summarized and further constructed
      into a three-class index (good, moderate and poor dietary quality) where higher
      scores depicted better diet quality. The CIDQ cut-off score of 14 points for good
      dietary quality had a sensitivity of 0.59 and a specificity of 0.82 and the cut
      off score of 10 points, for at least moderate dietary quality, had a sensitivity
      of 0.77 and a specificity of 0.69. Higher index scores were related to higher
      dietary intakes of several vitamins, lower dietary intakes of SFA and
      cholesterol, and further with lower serum cholesterol and higher serum vitamin C
      concentrations. CONCLUSIONS: The three-class food index was found to represent
      diet quality as defined in recommendations and evaluated against nutrient intakes
      from food diaries and biochemical markers. This self-standing index could provide
      an effective and low-burden method to obtain information about diet quality and
      guide future recommendations.

PMID- 25584443
TI  - Antimicrobial stewardship for neonates and children: a global approach.

PMID- 25584444
TI  - The road to certification.

PMID- 25584445
TI  - Reap the benefits of certification.

PMID- 25584447
TI  - Geriatric preinjury activities of daily living function is associated with
      glasgow coma score and discharge disposition: a retrospective, consecutive cohort
      study.
AB  - The primary objective was to evaluate the associations of the Injury Severity
      Score (ISS), age, Glasgow Coma Score (GCS), preexisting medical conditions
      (PEMC), and preinjury activities of daily living (ADL) Katz score with discharge
      disposition in surviving geriatric trauma patients.Data were obtained from the
      trauma registry. The preinjury Katz ADL score was prospectively ascertained.Of
      184 consecutive surviving geriatric trauma patients with an ISS of 4 to 30, age
      was 80 +/- 8 years and 75% fell. A PEMC was present in 93%. Preinjury ADL
      limitation occurred in 33%. The Katz score had inverse associations with the
      number of PEMCs (P< .01) and dementia (P < .01). Preinjury residence was home in
      93% and nursing home in 7%. Katz scores by discharge disposition were as follows:
      home (36%) 5.5 +/- 1; nursing home (15%) 3.6 +/- 2; rehabilitation (44%) 5.6 +/-
      1; long-term acute care (5%) 4.0 +/- 3 (P < .01). Nursing home/long-term acute
      care discharge was independently associated (P< .01) withlower Katz score, higher
      age, and lower discharge GCS; dementia and the number of PEMCs had P > .05. The
      discharge GCS was associated with the Katz score (P < .01), head injury score (P
      < .01), dementia (P < .01), and admission GCS (P < .01). The discharge GCS was
      independently associated (P < .01) with the Katz score and admission GCS. The
      admission GCS was associated with the Katz score (P = .02), ISS (P < .01), head
      injury score (P < .01), and dementia (P < .01). The admission GCS was
      independently associated (P < .05) with the Katz score and ISS.The majority of
      geriatric trauma survivors with an ISS of 4 to 30 are not discharged home. Lower
      preinjury ADL function is associated with the lower admission and discharge GCS
      and greater care needs at discharge. Dementia and the number of PEMCs are not
      independent predictors of discharge disposition.

PMID- 25584448
TI  - Successful percutaneous management of traumatic abdominal compartment syndrome in
      a child.
AB  - Posttraumatic abdominal compartment syndrome (ACS) is an unusual and potentially
      lethal entity in pediatric patients. Early recognition and/or prevention of the
      syndrome, as well as prompt treatment of ACS, can reduce its associated morbidity
      and mortality but has traditionally required a laparotomy. Herein, we describe a
      case of posttraumatic ACS successfully treated percutaneously.

PMID- 25584449
TI  - Evaluation and treatment of depression in adult trauma patients.
AB  - A retrospective study examined in-hospital antidepressant medication (ADM) use in
      adult trauma patients with an intensive care unit stay of 5 or more days. One
      fourth of patients received an ADM, with only 33% of those patients having a
      documented history of depression. Of patients who received their first ADM from a
      trauma or critical care physician, only 5% were discharged with a documented plan
      for psychiatric follow-up. The study identified a need for standardized
      identification and management of depressive symptoms among trauma patients in the
      inpatient setting. 

PMID- 25584450
TI  - A multidisciplinary approach to providing care to adolescents with spinal cord
      trauma resulting from all-terrain vehicle accidents.
AB  - All-terrain vehicle accidents that affect the spine can lead to complex injuries
      in adolescents. This requires that many subspecialties work together on a
      multidisciplinary team to improve patient outcomes. Our case presentation will
      examine the multidisciplinary approach to care required for an 11-year-old
      adolescent involved in an all-terrain vehicle accident that resulted in traumatic
      spinal cord injury.

PMID- 25584451
TI  - Using a new evidence-based trauma protocol to improve detection and reduce costs
      in patients with blunt cardiac injury.
AB  - INTRODUCTION: Management of blunt cardiac injury is often discussed in trauma
      literature due to the lack of a "gold standard" for early identification and cost
      effective care. The effectiveness of an evidence-based trauma protocol was
      assessed by comparing patients treated with the new protocol to those managed
      with prior practice. METHODS: The data of 80 patients prospectively managed using
      the new trauma protocol were compared with the medical records of 80 former
      patients treated according to existing practice. RESULTS: Implementing the new
      protocol improved detection of abnormal troponin I levels and resulted in cost
      savings. The length of time inpatients required continuous electrocardiographic
      monitoring decreased by 4.23 days and echocardiography use dropped by 70%.
      CONCLUSION: Implementation of the evidence-based trauma protocol at our facility
      improved the early identification of patients with blunt cardiac injury and
      reduced the number of laboratory and diagnostic tests.

PMID- 25584452
TI  - Designing a disaster.
AB  - A mass casualty simulation was developed and implemented for senior-level nursing
      students in a large baccalaureate program. This simulation was developed to
      introduce students to rapid triage in an interactive and immersive experience.
      The purpose of the simulation was to provide students with a realistic, hands-on
      experience in a safe environment. Unlike other similar exercises, all students
      participated in the health care provider role rather than as observers or
      victims. Didactic content regarding triage and a short video preceded the
      surprise simulated "bus crash." The element of surprise was used to create the
      chaos and confusion that often accompanies these incidents. Fifteen victims were
      comprised of static manikins, high-fidelity human patient simulators, and live
      actors with various injuries. The students worked in small groups and assigned
      each victim an appropriate Simple Triage and Rapid Treatment triage category on
      the basis of what they learned in lecture. Participating students performed well
      on their final examinations on questions covering the triage content they learned
      in this unit and feedback regarding the simulated experience was overwhelmingly
      positive. This simulation could be adapted for the education of other health care
      providers who may be involved in a future mass casualty incident.

PMID- 25584453
TI  - Complete tracheal transection following blunt trauma in a pediatric patient.
AB  - Tracheal injury from blunt trauma is a rare, life-threatening condition in
      pediatric patients. Rapid assessment and identification of the severity of the
      injury will increase the likelihood of survival. Subcutaneous emphysema,
      pneumomediastinum, and persistent pneumothoraces after chest tube placement
      should be considered in the index of suspicion for tracheal injury. Treatment for
      a complete tracheal transection includes rapid airway securement via endotracheal
      tube or tracheostomy and careful surgical repair in the operating room in
      conjunction with bronchoscopy.

PMID- 25584454
TI  - Knowledge on dental trauma management and caries prevention.
AB  - PURPOSE: This study evaluated the knowledge of dental assistants (DA) and
      hygienists (DH) on dental trauma management and dental caries prevention.
      Secondarily, other aims were 2-fold: (1) to update the assistants/hygienists
      through courses supported on scientific evidence-based information and (2) to
      evaluate their job satisfaction. METHODS: A cross-sectional study was conducted
      with 46 participants, DHs and Das, working in the Secretary of Education of the
      city of Brasilia (Federal District, Brazil). The information was gathered through
      2 self-administered questionnaires during 2 training meetings. The first
      questionnaire was applied before the first meeting and the second questionnaire
      after the last meeting. All participants were women older than 38 years and with
      more than 15 years of experience. RESULTS: The participants demonstrated
      knowledge on dental trauma types but lack of knowledge on dental trauma first-aid
      approaches. Concerning to dental caries, the professional demonstrated knowledge
      on both etiology and prevention. CONCLUSION: Lectures, periodical training, and
      inclusion in multidisciplinary training groups aiming to caries prevention and
      dental trauma are necessary.

PMID- 25584455
TI  - A new way to look at rural trauma spending: how specific spending and training
      can improve patient care and staff abilities.

PMID- 25584458
TI  - Use of milrinone in neonatal intensive care medicine.

PMID- 25584459
TI  - Anti-Xa activity in VTE patients treated with fondaparinux.

PMID- 25584460
TI  - The role of the gut microbiome in the healthy adult status.
AB  - The gut microbiome, which hosts up to 1000 bacterial species that encode about 5
      million genes, perform many of the functions required for host physiology and
      survival. Consequently, it is also known as "our forgotten organ". The recent
      development of next-generation sequencing technologies has greatly improved
      metagenomic research. In particular, it has increased our knowledge about the
      microbiome and its mutually beneficial relationships with the human host.
      Microbial colonization begins immediately at birth. Although influenced by a
      variety of stimuli, namely, diet, physical activity, travel, illness, hormonal
      cycles and therapies, the microbiome is practically stable in healthy adults.
      This suggests that the microbiome plays a role in the maintenance of a healthy
      state in adulthood. Quantitative and qualitative alterations in the composition
      of the gut microbiome could lead to pathological dysbiosis, and have been related
      to an increasing number of intestinal and extra-intestinal diseases. With the
      increase in knowledge about gut microbiome functions, it is becoming increasingly
      more possible to develop novel diagnostic, prognostic and, most important,
      therapeutic strategies based on microbiome manipulation. 

PMID- 25584462
TI  - Teaching for the future.
AB  - Reading and discussing classic papers can be an effective way of teaching
      graduate students how to learn the skills they will need for a career in
      research, as. 

PMID- 25584463
TI  - RETRACTED: Fueling doubt and openness: experiencing the unconscious, constructed
      nature of perception induces uncertainty and openness to change.
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy).The article has been retracted
      at the request of the Editor-in-Chief, Steven Sloman, following a request by the
      authors. The reason for the retraction is that the article includes fabricated or
      manipulated data.

PMID- 25584461
TI  - Delay-dependent contributions of medial temporal lobe regions to episodic memory
      retrieval.
AB  - The medial temporal lobes play an important role in episodic memory, but over
      time, hippocampal contributions to retrieval may be diminished. However, it is
      unclear whether such changes are related to the ability to retrieve contextual
      information, and whether they are common across all medial temporal regions.
      Here, we used functional neuroimaging to compare neural responses during
      immediate and delayed recognition. Results showed that recollection-related
      activity in the posterior hippocampus declined after a 1-day delay. In contrast,
      activity was relatively stable in the anterior hippocampus and in neocortical
      areas. Multi-voxel pattern similarity analyses also revealed that anterior
      hippocampal patterns contained information about context during item recognition,
      and after a delay, context coding in this region was related to successful
      retention of context information. Together, these findings suggest that the
      anterior and posterior hippocampus have different contributions to memory over
      time and that neurobiological models of memory must account for these
      differences. 

PMID- 25584464
TI  - Distinctive voices enhance the visual recognition of unfamiliar faces.
AB  - Several studies have provided evidence in favour of a norm-based representation
      of faces in memory. However, such models have hitherto failed to take account of
      how other person-relevant information affects face recognition performance. Here
      we investigated whether distinctive or typical auditory stimuli affect the
      subsequent recognition of previously unfamiliar faces and whether the type of
      auditory stimulus matters. In this study participants learned to associate either
      unfamiliar distinctive and typical voices or unfamiliar distinctive and typical
      sounds to unfamiliar faces. The results indicated that recognition performance
      was better to faces previously paired with distinctive than with typical voices
      but we failed to find any benefit on face recognition when the faces were
      previously associated with distinctive sounds. These findings possibly point to
      an expertise effect, as faces are usually associated to voices. More importantly,
      it suggests that the memory for visual faces can be modified by the perceptual
      quality of related vocal information and more specifically that facial
      distinctiveness can be of a multi-sensory nature. These results have important
      implications for our understanding of the structure of memory for person
      identification. 

PMID- 25584466
TI  - Letter from the editor.

PMID- 25584467
TI  - Leadership development in UK medical training: pedagogical theory and practice.
AB  - PHENOMENON: The central role of clinical leadership in achieving the vision of
      quality and productivity could be attained by investing in its development in
      postgraduate medical education. APPROACH: A critical review of selected
      literature is presented. FINDINGS: The author identifies some of the main
      theoretical constructs related to leadership; the pedagogical underpinning of
      medical leadership programs; their learning objectives; and the mixture of
      methods, individual and collective, to achieve them. INSIGHTS: How to best
      develop leadership through medical education remains an open debate. Experiential
      learning, reflective practice, action learning, and mentoring could provide the
      foundations of leadership development. Application of the aforementioned should
      be cautious due to limitations of the concept of leadership as currently promoted
      and lack of robust evaluation methodologies.

PMID- 25584468
TI  - A review of training research and virtual reality simulators for the da Vinci
      surgical system.
AB  - PHENOMENON: Virtual reality simulators are the subject of several recent studies
      of skills training for robot-assisted surgery. Yet no consensus exists regarding
      what a core skill set comprises or how to measure skill performance. Defining a
      core skill set and relevant metrics would help surgical educators evaluate
      different simulators. APPROACH: This review draws from published research to
      propose a core technical skill set for using the da Vinci surgeon console.
      Publications on three commercial simulators were used to evaluate the simulators'
      content addressing these skills and associated metrics. FINDINGS: An analysis of
      published research suggests that a core technical skill set for operating the
      surgeon console includes bimanual wristed manipulation, camera control, master
      clutching to manage hand position, use of third instrument arm, activating energy
      sources, appropriate depth perception, and awareness of forces applied by
      instruments. Validity studies of three commercial virtual reality simulators for
      robot-assisted surgery suggest that all three have comparable content and
      metrics. However, none have comprehensive content and metrics for all core
      skills. INSIGHTS: Virtual reality simulation remains a promising tool to support
      skill training for robot-assisted surgery, yet existing commercial simulator
      content is inadequate for performing and assessing a comprehensive basic skill
      set. The results of this evaluation help identify opportunities and challenges
      that exist for future developments in virtual reality simulation for robot
      assisted surgery. Specifically, the inclusion of educational experts in the
      development cycle alongside clinical and technological experts is recommended.

PMID- 25584469
TI  - Preparation for a postgraduate specialty examination by medical students in
      Turkey: processes and sources of anxiety.
AB  - PHENOMENON: Interns in Turkey must endeavor to study for a specialty exam during
      their internship. The preparation process for the specialty exam and the effect
      of this process on the students' anxiety has not been studied comprehensively.
      The purpose of this study was to evaluate the interns' preparation time for the
      specialty exam, their perception of how the preparation process affects their
      training, and which factors are related to their test anxiety. APPROACH: A cross
      sectional study was conducted with 6th-year students (interns). A questionnaire
      asked participants to report health status, academic achievement, exam-related
      anxiety, and trait anxiety. Two open-ended questions asked about views regarding
      the specialty exam. Multiple linear regression was used to identify the
      significant predictors of anxiety level due to the exam. FINDINGS: The average
      duration of exam preparations of participating interns (n = 214) was 16.8 months
      and 14.3 hours/week. Participating interns' health status, economic level,
      perception of academic achievement, time allocated to study for the exam, time
      remaining until the exam, and trait anxiety level demonstrated a relationship
      with anxiety level due to the exam (R =.35, R(2) =.13, p <.001). In the open
      ended questions, the most frequent opinion regarding the importance of the
      Examination for Specialty in Medicine was "Value attributed to specialization"
      (43%). The most frequent response regarding the contribution of studying for the
      specialty exam to their general professional skills was "Rehearsal/recall."
      INSIGHTS: Participating interns spent an appreciable amount of time preparing for
      the specialty exam. Although participating interns value this exam, they appear
      to believe that preparing for it will contribute only moderately to their
      professional competencies, while increasing their anxiety level. The internship
      curriculum, requirements, and timing of the specialty exam should be
      reconsidered.

PMID- 25584470
TI  - The effect of resident duty-hours restrictions on internal medicine clerkship
      experiences: surveys of medical students and clerkship directors.
AB  - PHENOMENON: Medical students receive much of their inpatient teaching from
      residents who now experience restructured teaching services to accommodate the
      2011 duty-hour regulations (DHR). The effect of DHR on medical student
      educational experiences is unknown. We examined medical students' and clerkship
      directors' perceptions of the effects of the 2011 DHR on internal medicine
      clerkship students' experiences with teaching, feedback and evaluation, and
      patient care. APPROACH: Students at 14 institutions responded to surveys after
      their medicine clerkship or subinternship. Students who completed their clerkship
      (n = 839) and subinternship (n = 228) March to June 2011 (pre-DHR historical
      controls) were compared to clerkship students (n = 895) and subinterns (n = 377)
      completing these rotations March to June 2012 (post-DHR). Z tests for proportions
      correcting for multiple comparisons were performed to assess attitude changes.
      The Clerkship Directors in Internal Medicine annual survey queried institutional
      members about the 2011 DHR just after implementation. FINDINGS: Survey response
      rates were 64% and 50% for clerkship students and 60% and 48% for subinterns in
      2011 and 2012 respectively, and 82% (99/121) for clerkship directors. Post-DHR,
      more clerkship students agreed that attendings (p =.011) and interns (p =.044)
      provided effective teaching. Clerkship students (p =.013) and subinterns (p
      =.001) believed patient care became more fragmented. The percentage of holdover
      patients clerkship students (p =.001) and subinterns (p =.012) admitted
      increased. Clerkship directors perceived negative effects of DHR for students on
      all survey items. Most disagreed that interns (63.1%), residents (67.8%), or
      attendings (71.1%) had more time to teach. Most disagreed that students received
      more feedback from interns (56.0%) or residents (58.2%). Fifty-nine percent felt
      that students participated in more patient handoffs. INSIGHTS: Students perceive
      few adverse consequences of the 2011 DHR on their internal medicine experiences,
      whereas their clerkship director educators have negative perceptions. Future
      research should explore the impact of fragmented patient care on the student
      patient relationship and students' clinical skills acquisition.

PMID- 25584471
TI  - Assessment of lumbar puncture skill in experts and nonexperts using checklists
      and quantitative tracking of needle trajectories: implications for competency
      based medical education.
AB  - CONSTRUCT: With the current shift toward competency-based education, rigorous
      assessment tools are needed for procedurally based tasks. BACKGROUND: Multiple
      tools exist to evaluate procedural skills, each with specific weaknesses.
      APPROACH: We sought to determine if quantitative needle tracking could be used as
      a measure of lumbar puncture (LP) performance and added discriminatory value to a
      dichotomous checklist. Thirty-two medical students were divided into 2 groups.
      One group was asked to practice an LP once (single practice [SP]) and the other 5
      times (multiple practice [MP]). Experts (attending ER physicians, senior ER
      residents, and a junior anesthesia resident) were used as comparators. Medical
      students were assessed again at 1 month to assess skill retention. Groups were
      assessed performing an LP with an electromagnetic tracking device that allows the
      needle's 3-dimensional movements to be captured and analyzed, and a dichotomous
      checklist. RESULTS: Quantitative needle metrics as assessed by electromagnetic
      tracking showed a decreasing trend in needle movement distance with practice and
      with experience. The SP group made significantly more checklist mistakes
      initially as compared to the MP group (1.2 vs. 0.3, p <.05). At 1 month, there
      was a significant increase in both groups' mistakes (SP 3.4 vs. MP 1.3, p =.01).
      No correlation existed between individuals' needle motion and checklist mistakes.
      CONCLUSIONS: These findings suggest that quantitative needle tracking identifies
      students who struggle with needle insertion but are successful at completing the
      dichotomous checklist.

PMID- 25584472
TI  - Computer versus paper--does it make any difference in test performance?
AB  - CONSTRUCT: In this study, we examine the differences in test performance between
      the paper-based and the computer-based version of the Berlin formative Progress
      Test. In this context it is the first study that allows controlling for students'
      prior performance. BACKGROUND: Computer-based tests make possible a more
      efficient examination procedure for test administration and review. Although
      university staff will benefit largely from computer-based tests, the question
      arises if computer-based tests influence students' test performance. APPROACH: A
      total of 266 German students from the 9th and 10th semester of medicine
      (comparable with the 4th-year North American medical school schedule)
      participated in the study (paper = 132, computer = 134). The allocation of the
      test format was conducted as a randomized matched-pair design in which students
      were first sorted according to their prior test results. The organizational
      procedure, the examination conditions, the room, and seating arrangements, as
      well as the order of questions and answers, were identical in both groups.
      RESULTS: The sociodemographic variables and pretest scores of both groups were
      comparable. The test results from the paper and computer versions did not differ.
      The groups remained within the allotted time, but students using the computer
      version (particularly the high performers) needed significantly less time to
      complete the test. In addition, we found significant differences in guessing
      behavior. Low performers using the computer version guess significantly more than
      low-performing students in the paper-pencil version. CONCLUSIONS: Participants in
      computer-based tests are not at a disadvantage in terms of their test results.
      The computer-based test required less processing time. The reason for the longer
      processing time when using the paper-pencil version might be due to the time
      needed to write the answer down, controlling for transferring the answer
      correctly. It is still not known why students using the computer version
      (particularly low-performing students) guess at a higher rate. Further studies
      are necessary to understand this finding.

PMID- 25584473
TI  - Do medical student stress, health, or quality of life foretell step 1 scores? A
      comparison of students in traditional and revised preclinical curricula.
AB  - THEORY: We explored the theory that measures of medical students' well-being and
      stress from different types of preclinical curricula are linked with performance
      on standardized assessment. HYPOTHESES: Self-reported stress and quality of life
      among sophomore medical students having different types of preclinical curricula
      will vary in their relationships to USMLE Step 1 scores. METHOD: Voluntary
      surveys in 2010 and 2011 compared self-reported stress, physical and mental
      health, and quality of life with Step 1 scores for beginning sophomore students
      in the final year of a traditional, discipline-based curriculum and the 1st year
      of a revised, systems-based curriculum with changed grading system. Wilcoxon rank
      sum tests and Spearman rank correlations were used to analyze data, significant
      at p <.05. RESULTS: New curriculum students reported worse physical health,
      subjective feelings, leisure activities, social relationships and morale, and
      more depressive symptoms and life stress than traditional curriculum students.
      However, among curriculum-related stressors, few differences emerged; revised
      curriculum sophomores reported less stress working with real and standardized
      patients than traditional students. There were no class differences in
      respondents' Step 1 scores. Among emotional and physical health measures, only
      feelings of morale correlated negatively with Step 1 performance. Revised
      curriculum students' Step 1 scores correlated negatively with stress from
      difficulty of coursework. CONCLUSIONS: Although revised curriculum students
      reported worse quality of life, general stress, and health and less stress from
      patient interactions than traditional students, few measures were associated with
      performance differences on Step 1. Moreover, curriculum type did not appear to
      either hinder or help students' Step 1 performance. To identify and help students
      at risk for academic problems, future assessments of correlates of Step 1
      performance should be repeated after the new curriculum is well established,
      relating them also to performance on other standardized assessments of
      communication skills, professionalism, and later clinical evaluations in
      clerkships or internships.

PMID- 25584475
TI  - Enhancing motivational interviewing training in a family medicine clerkship.
AB  - PROBLEM: Despite the prevalence of unhealthy behaviors among patients in the
      healthcare system, traditional medical training involves little or no exposure to
      effective behavior change techniques such as Motivational Interviewing.
      INTERVENTION: An online learning community for enhanced training in Motivational
      Interviewing was developed for 3rd-year medical students. The website included
      educational materials about Motivational Interviewing as well as problematic
      health behaviors, a repository of exemplar videos and student videos with
      feedback, and a discussion board. Student participants were given the opportunity
      to record an encounter with a patient and to receive feedback on their use of
      Motivational Interviewing from a faculty member. CONTEXT: Student volunteers in
      the Family Medicine Clerkship at Georgetown University School of Medicine were
      randomized to enhanced training, which included the online learning community, or
      training as usual. All student volunteers completed a questionnaire assessing
      self-efficacy initially and at the end of the clerkship. Students also
      participated in an Observed Structured Clinical Exam, which was subsequently
      coded by a blinded rater for behavioral counts of Motivational Interviewing
      techniques, key steps in Motivational Interviewing, and overall Motivational
      Interviewing style. OUTCOME: Students in the enhanced training arm were rated as
      having significantly higher scores in Motivational Interviewing style in the
      Observed Structured Clinical Exam than training as usual students. A significant
      increase in self-efficacy from pre- to posttest in the overall sample was
      observed but between-group differences were not significant. Student feedback was
      particularly positive regarding video recorded practice sessions with patients
      and individualized feedback. LESSONS LEARNED: The results of this study as well
      as student feedback suggest that future work should include patient practice
      sessions and individualized feedback in developing Motivational Interviewing
      curricula.

PMID- 25584474
TI  - Use of a checklist during observation of a simulated cardiac arrest scenario does
      not improve time to CPR and defibrillation over observation alone for subsequent
      scenarios.
AB  - THEORY: Immersive simulation is a common mode of education for medical students.
      Observation of clinical simulations prior to participation is believed to be
      beneficial, though this is often a passive process. Active observation may be
      more beneficial. HYPOTHESES: The hypothesis tested in this study was that the
      active use of a simple checklist during observation of an immersive simulation
      would result in better participant performance in a subsequent scenario compared
      with passive observation alone. METHODS: Medical students were randomized to
      either passive or active (with checklist) observation of an immersive simulation
      involving cardiac arrest prior to participating in their own simulation.
      Performance measures included time to cardiopulmonary resuscitation (CPR) and
      time to defibrillation and were compared between first and second scenarios as
      well as between passive and active observers. RESULTS: Seventy-nine simulations
      involving 232 students were conducted. Mean time to CPR was 18 seconds (SD =
      11.6) for those using the checklist and 24 seconds (SD = 15.8) for those who
      observed passively (M difference = 6 seconds), t(35) = 1.46, p =.153. Time to
      defibrillation was 94 seconds (SD = 26.4) for those using the checklist and 92
      seconds (SD = 23.8) for those who observed passively (M difference = -2 seconds),
      t(38) =.21, p =.837. Time to CPR was 24 seconds (SD = 15.8) for passive observers
      and 31 seconds (SD = 21.0; M difference = 7 seconds), t(35) = 1.13, p =.265, for
      their first scenario counterparts. Time to CPR was 18 seconds (SD = 11.6) for
      active observers and 36 seconds (SD = 26.2; M difference = 18 seconds), t(24) =
      2.81, p =.010, for their first scenario counterparts. Time to defibrillation was
      92 seconds (SD = 23.8) for passive observers and 125 seconds (SD = 32.2; M
      difference = 33 seconds), t(33) = 3.63, p =.001, for their first scenario
      counterparts. Time to defibrillation was 94 seconds (SD = 26.4) for the active
      observers and 132 seconds (SD = 52.9; M difference = 38 seconds), t(28) =.46, p
      =.008, for their first scenario counterparts. CONCLUSIONS: Observation alone
      leads to improved performance in the management of a simulated cardiac arrest.
      The active use of a simple skills-based checklist during observation did not
      appear to improve performance over passive observation alone.

PMID- 25584476
TI  - Development, evaluation, and delivery of an innovative national undergraduate
      surgical workshop: recognition and management of the acutely unwell surgical
      patient.
AB  - PROBLEM: Recognition and management of acutely unwell surgical patients is an
      important skill to which medical students have little exposure. INTERVENTION: We
      present the evaluation of a novel national surgical workshop that consisted of
      high-fidelity simulations, lectures, case demonstrations, case discussions, and a
      basic surgical skills tutorial. The high-fidelity simulations re-created genuine
      patient encounters and were used to facilitate the acquisition of knowledge and
      skill in the early recognition and management of acutely unwell surgical
      patients. CONTEXT: The optional workshop was designed for senior medical students
      and delivered by surgical trainees. Students were asked to complete a 12-item
      evaluation questionnaire and a 26-item multiple-choice question (MCQ) quiz, which
      assessed their confidence; self-perceived competence; and knowledge prior to,
      immediately following, and 8 weeks after the workshop. Pre- and postdata were
      compared using student's two-tailed t test. OUTCOME: A total of 66 medical
      students from 6 UK universities attended, the majority of whom enjoyed the
      workshop (98.3%, n = 59). Participants' confidence rating (scale = 1-5) in
      assessing an unwell surgical patient improved from a mean of 2.5 (n = 47) to 4.4
      (n = 60). Confidence in commencing initial management improved from a mean of 2.7
      (n = 47) to 4.1 (n = 59). Confidence and self-perceived competence across 12
      domains improved significantly following the workshop, two-tailed unpaired t
      test, t(22) = 8.64, p <.0001, d = 3.68. MCQ scores immediately following the
      workshop were a statistically significant improvement on the preworkshop MCQ
      scores (n = 44), paired two-tailed t test, t(43) = 7.76, p <.0001, d = 2.37, and
      the improvement was sustained 8 weeks following the workshop (n = 18), paired two
      tailed t test, t(17) = 3.34, p =.0039, d = 1.62. LESSONS LEARNED: Feedback from
      students was very positive and clearly demonstrated that a workshop taught by
      surgical trainees improved medical students' confidence, self-perceived
      competence, and knowledge in the assessment and management of acutely unwell
      surgical patients.

PMID- 25584477
TI  - University of Saskatchewan Radiology Courseware (USRC): an assessment of its
      utility for teaching diagnostic imaging in the medical school curriculum.
AB  - PROBLEM: We have found it very challenging to integrate images from our radiology
      digital imaging repository into the curriculum of our local medical school. Thus,
      it has been difficult to convey important knowledge related to viewing and
      interpreting diagnostic radiology images. We sought to determine if we could
      create a solution for this problem and evaluate whether students exposed to this
      solution were able to learn imaging concepts pertinent to medical practice.
      INTERVENTION: We developed University of Saskatchewan Radiology Courseware
      (USRC), a novel interactive web application that enables preclinical medical
      students to acquire image interpretation skills fundamental to clinical practice.
      This web application reformats content stored in Medical Imaging Resource Center
      teaching cases for BlackBoard LearnTM, a popular learning management system. We
      have deployed this solution for 2 successive years in a 1st-year basic sciences
      medical school course at the College of Medicine, University of Saskatchewan. The
      "courseware" content covers both normal anatomy and common clinical pathologies
      in five distinct modules. We created two cohorts of learners consisting of an
      intervention cohort of students who had used USRC for their 1st academic year,
      whereas the nonintervention cohort was students who had not been exposed to this
      learning opportunity. CONTEXT: To assess the learning experience of the users we
      designed an online questionnaire and image review quiz delivered to both of the
      student groups. OUTCOME: Comparisons between the groups revealed statistically
      significant differences in both confidence with image interpretation and the
      ability to answer knowledge-based questions. Students were satisfied with the
      overall usability, functions, and capabilities of USRC. LESSONS LEARNED: USRC is
      an innovative technology that provides integration between Medical Imaging
      Resource Center, a teaching solution used in radiology, and a Learning Management
      System.

PMID- 25584478
TI  - Introversion and medical student education: challenges for both students and
      educators.
AB  - ISSUE: Introversion is one of the personality factors that has been shown to be
      associated with performance in medical school. Prior cross-sectional studies
      highlight performance evaluation differences between introverted and extraverted
      medical students, though the mechanisms and implications of these differences
      remain relatively unexplained and understudied. This gap in the literature has
      become more salient as medical schools are employing more interactive learning
      strategies into their curricula which may disproportionately challenge
      introverted learners. EVIDENCE: In this article, we provide an overview and
      working definition of introversion as a valid construct occurring on a continuum.
      We apply a goodness of fit model to explore how various medical training contexts
      may be more or less challenging for introverted students and the potential
      consequences of a poor fit. As preliminary support for these hypothesized
      challenges, we share observations from students self-identified as introverts.
      Examples include introverted students feeling at times like misfits, questioning
      a need to change their identity to succeed in medical school, and being judged as
      underperformers. We offer pragmatic suggestions for improving the fit between
      introverted students and their training contexts, such as teachers and students
      pausing between a question being asked and the initial response being offered and
      teachers differentiating between anxious and introverted behaviors. We conclude
      with suggested areas for future qualitative and quantitative research to examine
      how medical school curricula and the teaching environment may be differentially
      impacting the learning and health of introverted and extraverted students.
      IMPLICATIONS: Extraverted behaviors will continue to be an important part of
      medical training and practice, but the merits of introverted behaviors warrant
      further consideration as both medical training and practice evolve. Educators who
      make manageable adjustments to current teaching practices can improve the
      learning for both introverted and extraverted styles of academic engagement.

PMID- 25584482
TI  - Highly efficient in-line magnetic domain wall injector.
AB  - We demonstrate a highly efficient and simple scheme for injecting domain walls
      into magnetic nanowires. The spin transfer torque from nanosecond long, unipolar,
      current pulses that cross a 90 degrees  magnetization boundary together with the
      fringing magnetic fields inherently prevalent at the boundary, allow for the
      injection of single or a continual stream of domain walls. Remarkably, the
      currents needed for this "in-line" domain wall injection scheme are at least one
      hundred times smaller than conventional methods. 

PMID- 25584483
TI  - 1H nuclear spin relaxation of liquid water from molecular dynamics simulations.
AB  - We have investigated the nuclear spin relaxation properties of (1)H in liquid
      water with the help of molecular dynamics simulations. We have computed the (1)H
      nuclear spin relaxation times T1 and T2 and determined the contribution of the
      different interactions to the relaxation at different temperatures and for
      different classical water models (SPC/E, TIP3P, TIP4P, and TIP4P/2005). Among the
      water models considered, the TIP4P/2005 model exhibits the best agreement with
      the experiment. The same analysis was performed with Car-Parrinello ab initio
      molecular dynamics simulations of bulk water at T = 330 K, which provided results
      close to the experimental values at room temperature. To complete the study, we
      have successfully accounted for the temperature-dependence of T1 and T2 in terms
      of a simplified model, which considers the reorientation in finite angle jumps
      and the diffusive translation of water molecules. 

PMID- 25584484
TI  - Combining clinicopathological predictors and molecular biomarkers in the
      oncogenic K-RAS/Ki67/HIF-1alpha pathway to predict survival in resectable
      pancreatic cancer.
AB  - BACKGROUND: The dismal prognosis of patients diagnosed with pancreatic cancer
      points to our limited arsenal of effective anticancer therapies. Oncogenic K-RAS
      hyperactivation is virtually universal in pancreatic cancer, that confers drug
      resistance, drives aggressive tumorigenesis and rapid metastasis. Pancreatic
      tumours are often marked by hypovascularity, increased hypoxia and ineffective
      drug delivery. Thus, biomarker discovery and developing innovative means of
      countervailing oncogenic K-RAS activation are urgently needed. METHODS: Tumour
      specimens from 147 pancreatic cancer patients were analysed by
      immunohistochemical (IHC) staining and tissue microarray (TMA). Statistical
      correlations between selected biomarkers and clinicopathological predictors were
      examined to predict survival. RESULTS: We find that heightened hypoxia response
      predicts poor clinical outcome in resectable pancreatic cancer. SIAH is a tumour
      specific biomarker. The combination of five biomarkers (EGFR, phospho-ERK, SIAH,
      Ki67 and HIF-1alpha) and four clinicopathological predictors (tumour size,
      pathological grade, margin and lymph node status) predict patient survival post
      surgery in pancreatic cancer. CONCLUSIONS: Combining five biomarkers in the K
      RAS/Ki67/HIF-1alpha pathways with four clinicopathological predictors may assist
      to better predict survival in resectable pancreatic cancer.

PMID- 25584485
TI  - Identification of a bona fide microRNA biomarker in serum exosomes that predicts
      hepatocellular carcinoma recurrence after liver transplantation.
AB  - BACKGROUND: Predictive biomarkers for the recurrence of hepatocellular carcinoma
      (HCC) have great benefit in the selection of treatment options, including liver
      transplantation (LT), for HCC. The purpose of this study was to identify specific
      microRNAs (miRs) in exosomes from the serum of patients with recurrent HCC and to
      validate these molecules as novel biomarkers for HCC recurrence. METHODS: We
      employed microarray-based expression profiling of miRs derived from exosomes in
      the serum of HCC patients to identify a biomarker that distinguishes between
      patients with and without HCC recurrence after LT. This was followed by the
      validation in a separate cohort of 59 HCC patients who underwent living related
      LT. The functions and potential gene targets of the recurrence-specific miRs were
      analysed using a database, clinical samples and HCC cell lines. RESULTS: We found
      that miR-718 showed significantly different expression in the serum exosomes of
      HCC cases with recurrence after LT compared with those without recurrence.
      Decreased expression of miR-718 was associated with HCC tumour aggressiveness in
      the validated cohort series. We identified HOXB8 as a potential target gene of
      miR-718, and its upregulation was associated with poor prognosis. CONCLUSION:
      Circulating miRs in serum exosomes have potential as novel biomarkers for
      predicting HCC recurrence.

PMID- 25584486
TI  - O6-Methylguanine-DNA methyltransferase status in neuroendocrine tumours:
      prognostic relevance and association with response to alkylating agents.
AB  - BACKGROUND: O(6)-Methylguanine-DNA methyltransferase (MGMT) loss of expression
      has been suggested to be predictive of response to temozolomide in neuroendocrine
      tumours (NETs), but so far, only limited data are available. We evaluated the
      prognostic and predictive value of MGMT status, assessed by two molecular methods
      and immunohistochemistry, in a large series of NETs of different origins.
      METHODS: A total of 107 patients, including 53 treated by alkylants
      (temozolomide, dacarbazine or streptozotocin), were retrospectively studied. In
      each case, we used methyl-specific PCR (MS-PCR) and pyrosequencing for evaluation
      of promoter methylation and immunohistochemistry for evaluation of protein
      status. RESULTS: MGMT promoter methylation was detected in 12 out of 99 (12%)
      interpretable cases by MS-PCR and in 24 out of 99 (24%) by pyrosequencing. O(6)
      Methylguanine-DNA methyltransferase loss of expression was observed in 29 out of
      89 (33%) interpretable cases. Status of MGMT was not correlated with overall
      survival (OS) from diagnosis. Progression-free survival and OS from first
      alkylant use (temozolomide, dacarbazine and streptozotocin) were higher in
      patients with MGMT protein loss (respectively, 20.2 vs 7.6 months, P<0.001 and
      105 vs 34 months, P=0.006) or MGMT promoter methylation assessed by
      pyrosequencing (respectively, 26.4 vs 10.8 months, P=0.002 and 77 vs 43 months,
      P=0.026). CONCLUSIONS: Our results suggest that MGMT status is associated with
      response to alkylant-based chemotherapy in NETs.

PMID- 25584487
TI  - Effect of aerobic training on the host systemic milieu in patients with solid
      tumours: an exploratory correlative study.
AB  - BACKGROUND: Few studies have investigated the effects of exercise on modulation
      of host factors in cancer patients. We investigated the efficacy of chronic
      aerobic training on multiple host-related effector pathways in patients with
      solid tumours. PATIENTS AND METHODS: Paired peripheral blood samples were
      obtained from 44 patients with solid tumours receiving cytotoxic therapy and
      synthetic erythropoietin (usual care; n=21) or usual care plus supervised aerobic
      training (n=23) for 12 weeks. Samples were characterised for changes in immune,
      cytokine and angiogenic factors, and metabolic intermediates. Aerobic training
      consisted of three supervised cycle ergometry sessions per week at 60% to 100% of
      peak oxygen consumption (VO2peak), 30-45 min per session, for 12 weeks following
      a nonlinear prescription. RESULTS: The between-group delta change in
      cardiopulmonary function was +4.1 ml kg (-1) min(-1), favouring aerobic training
      (P<0.05). Significant pre-post between-group differences for five cytokine and
      angiogenic factors (HGF, IL-4, macrophage inflammatory protein-1beta (MIP-1beta),
      vascular endothelial growth factor (VEGF), and TNF-alpha) also favour the aerobic
      training group (P's<0.05). These reductions occurred in conjunction with
      nonsignificant group differences for T lymphocytes CD4(+), CD8(+), and
      CD8(+)/CD45RA (P<0.10). For these factors, circulating concentrations generally
      increased from baseline to week 12 in the aerobic training group compared with
      decreases or no change in the usual care group. No significant changes in any
      metabolic intermediates were observed. CONCLUSIONS: Aerobic training alters host
      availability of select immune-inflammatory effectors in patients with solid
      tumours; larger confirmatory studies in more homogenous samples are warranted.

PMID- 25584488
TI  - Effect of adjuvant trastuzumab among patients treated with anti-HER2-based
      neoadjuvant therapy.
AB  - PURPOSE: To study the impact of adjuvant trastuzumab among patients achieving a
      pathologic complete response (pCR) after trastuzumab-based neoadjuvant systemic
      therapy (NST). PATIENTS AND METHODS: Patients with primary HER2-positive breast
      cancer treated with trastuzumab-based NST were categorised according to adjuvant
      trastuzumab administration and pCR status. Adjuvant trastuzumab became standard
      of care in 2006, this was the main reason patients in our cohort did not receive
      adjuvant trastuzumab. Kaplan-Meier was used to estimate survival. A test for
      interaction between adjuvant trastuzumab and pCR was completed. FINDINGS: Of 589
      patients, 203 (34.5%) achieved a pCR. After surgery, 109 (18.5%) patients in the
      entire cohort did not receive adjuvant trastuzumab. Among patients achieving a
      pCR, 31.3% received adjuvant trastuzumab compared with 68.8% among those who did
      not achieve a pCR (P=0.0006). Among patients achieving pCR, adjuvant trastuzumab
      did not further improve overall survival (OS) or relapse-free survival (RFS)
      (P=0.35 and P=0.93, respectively). Any benefit of adjuvant trastuzumab in OS and
      RFS among patients without a pCR did not achieve statistical significance (P=0.3
      and P=0.44, respectively). CONCLUSIONS: In this cohort, patients treated with
      trastuzumab-based NST who achieved a pCR have excellent outcome regardless of
      whether they received adjuvant trastuzumab.

PMID- 25584489
TI  - Exposure-response analysis of rilotumumab in gastric cancer: the role of tumour
      MET expression.
AB  - BACKGROUND: Rilotumumab, an investigational, monoclonal antibody, inhibits MET
      mediated signalling. In a randomized phase 2 trial of rilotumumab+/
      epirubicin/cisplatin/capecitabine in gastric or oesophagogastric junction cancer,
      patients receiving rilotumumab showed a trend towards improved survival,
      especially in MET-positive patients, but no clear dose-response relationship was
      observed. Exposure-response and biomarker analyses were used for dose selection
      and to differentiate patient subpopulations that may benefit most from treatment.
      Here, we analyse rilotumumab exposure-survival and exposure-safety and the impact
      of MET expression on these relationships. METHODS: Individual rilotumumab
      exposure parameters were generated using population pharmacokinetic modelling.
      Relationships among rilotumumab dose (7.5 and 15 mg kg(-1)), exposure, and
      clinical outcomes (progression-free survival (PFS) and overall survival (OS))
      were evaluated with Cox regression models and Kaplan-Meier plots. MET status and
      other baseline covariates were evaluated in subgroup and multivariate analyses.
      Treatment-emergent adverse events were summarised by exposure. RESULTS: Among MET
      positive patients, higher rilotumumab exposure, vs placebo and low exposure, was
      associated with improved median PFS (80% CI: 7.0 (5.7-9.7) vs 4.4 (2.9-4.9) and
      5.5 (4.2-6.8) months) and OS (13.4 (10.6-18.6) vs 5.7 (4.7-10.2) and 8.1 (6.9
      11.1) months) without increased toxicity. No rilotumumab benefit was seen among
      MET-negative patients. CONCLUSIONS: Rilotumumab had an exposure-dependent
      treatment effect in patients with MET-positive gastric or oesophagogastric
      junction cancer.

PMID- 25584491
TI  - Comment on: 'guidelines for the use of cell lines in biomedical research': human
      to-human cancer transmission as a laboratory safety concern.

PMID- 25584490
TI  - The prognostic value of pretreatment of systemic inflammatory responses in
      patients with urothelial carcinoma undergoing radical cystectomy.
AB  - BACKGROUND: Systemic inflammatory response (SIR) is important in the relationship
      between the tumour, the host, and outcome in cancer patients. However, limited
      data exist regarding the prognostic significance of SIR in bladder cancer. We
      investigate the utility of pretreatment SIR in patients with urothelial carcinoma
      undergoing radical cystectomy. METHODS: The study cohort consisted of 419
      patients with a median follow-up of 37.7 months. The SIRs used for each described
      prognostic nomogram are consistent with previously published data: C-reactive
      protein, albumin, white cell count, neutrophil count, lymphocyte count, and
      platelet count. Primary end point was disease-specific survival (DSS) and overall
      survival (OS) after surgery. Cox regression models were used to determine the
      time to disease-specific and overall mortality. Multivariate regression
      coefficients of the predictors were used to develop nomograms for predicting 5
      year DSS and OS probability. RESULTS: Multivariate Cox regression analyses
      revealed that albumin, lymphocyte count, and platelet count were significantly
      associated with a significantly increased risk for death from bladder cancer. The
      nomograms including each index were developed to predict the probability of 5
      year DSS and OS after radical cystectomy. The C statistics were 77.8% and 77.3%,
      respectively, and exceeded the 2002 AJCC (72.0% and 70.3%, respectively). In the
      decision curve analyses, the nomograms including SIR demonstrated higher net
      benefit gains compared with the models without SIR. CONCLUSIONS: Cellular
      components of SIR have better prognostic values compared with acute-phase protein
      in patients undergoing radical cystectomy for bladder cancer.

PMID- 25584492
TI  - Changes in circulating microRNA-126 during treatment with chemotherapy and
      bevacizumab predicts treatment response in patients with metastatic colorectal
      cancer.
AB  - BACKGROUND: This study investigated the predictive value of circulating microRNA
      126 (cir-miRNA-126) in patients with metastatic colorectal cancer (mCRC) treated
      with first-line chemotherapy combined with bevacizumab. METHODS: The study
      included 68 patients. Blood samples (plasma) were collected before the treatment
      initiation, at the first clinical evaluation after 3 weeks and at progression.
      Levels of cir-miRNA-126 were determined by qRT-PCR after purification of total
      RNA from plasma. Primary clinical end points were response rates evaluated
      according to the Response Evaluation Criteria In Solid Tumours (RECIST) and
      progression-free survival (PFS). RESULTS: Changes in circulating miRNA-126 during
      treatment were predictive of tumour response. Non-responding patients had a
      median increase in cir-miRNA-126 of 0.244 (95% confidence interval (CI), 0.050
      0.565) compared with a median decrease of -0.374 (95% CI, -0.472 to -0.111) in
      the responding patients, P=0.002. A significant positive correlation was
      demonstrated by comparing the changes in tumour size with the changes in cir
      miRNA-126, r=0.48, P=0.0001. Grouping the patients according to the changes in
      cir-miRNA-126 disclosed a borderline significant separation of the groups in the
      PFS analysis favouring patients with decreasing miRNA-126 levels, hazard ratio
      (HR) 0.60 (95% CI, 0.33-1.09), P=0.07. CONCLUSIONS: The present results indicate
      that changes in cir-miRNA-126 during treatment are related to the response to
      chemotherapy and bevacizumab in patients with mCRC, thus representing a possible
      biomarker for the resistance to anti-angiogenic containing treatments.

PMID- 25584493
TI  - Stem cells from adipose tissue and breast cancer: hype, risks and hope.
AB  - Several recent papers have generated new hope about the use of white adipose
      tissue (WAT)-derived progenitor cells for soft tissue reconstruction in a variety
      of diseases including breast cancer (BC), a procedure that is increasingly used
      worldwide. We revised the available literature about WAT cells and BC. In the BC
      field, we believe that the hype for the exciting results in terms of WAT
      progenitor cell engraftment and tissue augmentation should be tempered when
      considering the recent and abundant preclinical studies, indicating that WAT
      progenitors may promote BC growth and metastasis. White adipose tissue
      progenitors can contribute to tumour vessels, pericytes and adipocytes, and were
      found to stimulate local and metastatic BC progression in several murine models.
      Moreover, there are clinical retrospective data showing a significant increase in
      the local recurrence frequency in patients with intraepithelial neoplasia who
      received a lipofilling procedure for breast reconstruction compared with
      controls. Retrospective and prospective clinical trials are warranted to
      investigate in depth the safety of this procedure in BC. Preclinical models
      should be used to find mechanisms able to inhibit the tumour-promoting activity
      of WAT progenitors while sparing their tissue reconstruction potential. 

PMID- 25584494
TI  - Evaluation of chemoresponse assays as predictive markers.
AB  - BACKGROUND: A chemoresponse assay that can be used to predict which patients will
      respond to which drugs would be useful in directing treatment. Two new analytic
      methods to assess the predictive ability of a chemoresponse assay have been
      proposed by Tian et al. METHODS: Three examples in which a hypothetical assay has
      no predictive ability are considered to evaluate the properties of the proposed
      analytic methods. RESULTS: For these specific examples, the proposed methods
      incorrectly suggest that the assay is predictive. CONCLUSIONS: The examples
      presented here demonstrate that it can be challenging to evaluate the predictive
      value of a chemoresponse assay.

PMID- 25584495
TI  - Understanding Sociobehavioral Mitigators of Depressive Symptoms among U.S. Young
      Adults.
AB  - This study drew upon an ecological system framework to examine a model focusing
      on the interrelationship among depressive symptoms, sense of mastery, moderate-to
      vigorous physical activity (MVPA), religiosity, and relations with parents and
      romantic partners among U.S. young adults aged 24 to 34. Cross-sectional data
      from the National Longitudinal Study of Adolescent Health (N = 4,982), obtained
      in 2008 and 2009, were analyzed using structural equation modeling techniques.
      The associations of MVPA, relations with parents, and relations with romantic
      partner to depressive symptoms were mediated through mastery. Relations with
      one's romantic partner were a stronger predictor of depressive symptoms than
      relations with parents, while the influence of religiosity on relations with
      romantic partner was largely mediated by relations with parents. The results
      highlight the sociobehavioral buffers of depressive symptoms that are peculiar to
      young adulthood. Further intervention research in preventing and treating
      depressive symptoms should consider incorporating the sociobehavioral factors
      that are tailored to the specific age group.

PMID- 25584497
TI  - Wire-shaped ultraviolet photodetectors based on a nanostructured NiO/ZnO coaxial
      p-n heterojunction via thermal oxidation and hydrothermal growth processes.
AB  - We report the facile fabrication of wire-shaped ultraviolet photodetectors
      (WUPDs) by employing a nanostructured zinc oxide (ZnO)/nickel oxide (NiO) coaxial
      p-n heterojunction. The WUPD consists of a ZnO/NiO coaxial Ni wire and a twisted
      gold (Au) wire where the Ni and Au are used as the anode and cathode,
      respectively. For the coaxial p-n heterojunction, the NiO nanostructures (NSs)
      and the ZnO nanorods (NRs) are subsequently formed on the surface of Ni wire via
      thermal oxidation and hydrothermal growth processes. With an applied bias of -3.5
      V, the WUPD exhibits good photoresponsivity of 7.37 A W(-1) and an external
      quantum efficiency of 28.1% at an incident light wavelength of 325 nm. Under the
      UV illumination at a wavelength of 365 nm, the dark current and photocurrent are 
      3.97 * 10(-7) and -8.47 * 10(-6) A, respectively. For enhancing the photocurrent,
      the WUPD is threaded through a silver (Ag) coated glass tube which acts as a
      waveguide to concentrate the UV light of 365 nm on the WUPD. As a result, the
      photocurrent is significantly improved up to -1.56 * 10(-5) A (i.e., 1.84 times)
      at the reverse bias of -3.5 V. 

PMID- 25584496
TI  - Fluorescent flippers for mechanosensitive membrane probes.
AB  - In this report, "fluorescent flippers" are introduced to create planarizable push
      pull probes with the mechanosensitivity and fluorescence lifetime needed for
      practical use in biology. Twisted push-pull scaffolds with large and bright
      dithienothiophenes and their S,S-dioxides as the first "fluorescent flippers" are
      shown to report on the lateral organization of lipid bilayers with quantum yields
      above 80% and lifetimes above 4 ns. Their planarization in liquid-ordered (Lo)
      and solid-ordered (So) membranes results in red shifts in excitation of up to +80
      nm that can be transcribed into red shifts in emission of up to +140 nm by
      Forster resonance energy transfer (FRET). These unique properties are compatible
      with multidomain imaging in giant unilamellar vesicles (GUVs) and cells by
      confocal laser scanning or fluorescence lifetime imaging microscopy. Controls
      indicate that strong push-pull macrodipoles are important, operational probes do
      not relocate in response to lateral membrane reorganization, and two flippers are
      indeed needed to "really swim," i.e., achieve high mechanosensitivity. 

PMID- 25584498
TI  - Time-resolved Raman and polyacrylamide gel electrophoresis observations of
      nucleotide incorporation and misincorporation in RNA within a bacterial RNA
      polymerase crystal.
AB  - The bacterial RNA polymerase (RNAP) elongation complex (EC) is highly stable and
      is able to extend an RNA chain for thousands of nucleotides. Understanding the
      processive mechanism of nucleotide addition requires detailed structural and
      temporal data for the EC reaction. Here, a time-resolved Raman spectroscopic
      analysis is combined with polyacrylamide gel electrophoresis (PAGE) to monitor
      nucleotide addition in single crystals of the Thermus thermophilus EC (TthEC)
      RNAP. When the cognate base GTP, labeled with (13)C and (15)N (*GTP), is soaked
      into crystals of the TthEC, changes in the Raman spectra show evidence of
      nucleotide incorporation and product formation. The major change is the reduction
      of *GTP's triphosphate intensity. Nucleotide incorporation is confirmed by PAGE
      assays. Both Raman and PAGE methods have a time resolution of minutes. There is
      also Raman spectroscopic evidence of a second population of *GTP in the crystal
      that does not become covalently linked to the nascent RNA chain. When this
      population is removed by "soaking out" (placing the crystal in a solution that
      contains no NTP), there are no perturbations to the Raman difference spectra,
      indicating that conformational changes are not detected in the EC. In contrast,
      the misincorporation of the noncognate base, (13)C- and (15)N-labeled UTP (*UTP),
      gives rise to large spectroscopic changes. As in the GTP experiment, reduction of
      the triphosphate relative intensity in the Raman soak-in data shows that the
      incorporation reaction occurs during the first few minutes of our instrumental
      dead time. This is also confirmed by PAGE analysis. Whereas PAGE data show *GTP
      converts 100% of the nascent RNA 14mer to 15mer, the noncognate *UTP converts
      only ~50%. During *UTP soak-in, there is a slow, reversible formation of an alpha
      helical amide I band in the Raman difference spectra peaking at 40 min. Similar
      to *GTP soak-in, *UTP soak-in shows Raman spectoscopic evidence of a second
      noncovalently bound *UTP population in the crystal. Moreover, the second
      population has a marked effect on the complex's conformational states because
      removing it by "soaking-out" unreacted *UTP causes large changes in protein and
      nucleic acid Raman marker bands in the time range of 10-100 min. The
      conformational changes observed for noncognate *UTP may indicate that the enzyme
      is preparing for proofreading to excise the misincorporated base. This idea is
      supported by the PAGE results for *UTP soak-out that show endonuclease activity
      is occurring. 

PMID- 25584516
TI  - A review of m-health in medical imaging.
AB  - OBJECTIVE: The increasing capabilities of camera-equipped mobile phones have led
      to a growing body of evidence regarding their use in medical imaging across a
      broad range of medical specialties. This article reviews the current evidence for
      the use of mobile health (m-health) in medical imaging. MATERIALS AND METHODS: We
      performed a structured review of the published literature regarding m-health in
      medical imaging using the Medline, PubMed, and Web of Science databases (January
      2002-August 2013). The two authors independently extracted data regarding type of
      specialty, purpose, and study design of publications. RESULTS: In total, 235
      articles were identified. The majority of studies were case reports or
      noncomparative product validation studies. The greatest volume of publications
      originated in the fields of radiology (21%), dermatology (15%), laboratory
      techniques (15%), and plastic surgery (12%). Among these studies, m-health was
      used as diagnostic aids, for patient monitoring, and to improve communication
      between health practitioners. With the growing use of mobile phones for medical
      imaging, considerations need to be given to informed consent, privacy, image
      storage and transfer, and guidelines for healthcare workers and patients.
      CONCLUSIONS: There are several novel uses of mobile devices for medical imaging
      that show promise across a variety of areas and subspecialties of healthcare.
      Currently, studies are mostly exploratory in nature. To validate these devices,
      studies with higher methodological rigor are required.

PMID- 25584517
TI  - Amino acid coevolution reveals three-dimensional structure and functional domains
      of insect odorant receptors.
AB  - Insect odorant receptors (ORs) comprise an enormous protein family that
      translates environmental chemical signals into neuronal electrical activity.
      These heptahelical receptors are proposed to function as ligand-gated ion
      channels and/or to act metabotropically as G protein-coupled receptors (GPCRs).
      Resolving their signalling mechanism has been hampered by the lack of tertiary
      structural information and primary sequence similarity to other proteins. We use
      amino acid evolutionary covariation across these ORs to define restraints on
      structural proximity of residue pairs, which permit de novo generation of three
      dimensional models. The validity of our analysis is supported by the location of
      functionally important residues in highly constrained regions of the protein.
      Importantly, insect OR models exhibit a distinct transmembrane domain packing
      arrangement to that of canonical GPCRs, establishing the structural unrelatedness
      of these receptor families. The evolutionary couplings and models predict odour
      binding and ion conduction domains, and provide a template for rationale
      structure-activity dissection. 

PMID- 25584519
TI  - Transcriptomic response of Manduca sexta immune tissues to parasitization by the
      bracovirus associated wasp Cotesia congregata.
AB  - During oviposition, Cotesia congregata parasitoid wasps inject into their host,
      Manduca sexta, some biological factors such as venom, ovarian fluid and a
      symbiotic polydnavirus (PDV) named Cotesia congregata bracovirus (CcBV). During
      parasitism, complex interactions occur between wasp-derived factors and host
      targets that lead to important modifications in host physiology. In particular,
      the immune response leading to wasp egg encapsulation is inhibited allowing wasp
      survival. To date, the regulation of host genes during the interaction had only
      been studied for a limited number of genes. In this study, we analysed the global
      impact of parasitism on host gene regulation 24 h post oviposition by high
      throughput 454 transcriptomic analyses of two tissues known to be involved in the
      host immune response (hemocytes and fat body). To identify specific effects of
      parasitism on host transcription at this time point, transcriptomes were obtained
      from non-treated and parasitized larvae, and also from larvae injected with heat
      killed bacteria and double stimulated larvae that were parasitized prior to
      bacterial challenge. Results showed that, immune challenge by bacteria leads to
      induction of certain antimicrobial peptide (AMP) genes in M. sexta larvae whether
      they were parasitized or not prior to bacterial challenge. These results show
      that at 24 h post oviposition pathways leading to expression of AMP genes are not
      all inactivated suggesting wasps are in an antiseptic environment. In contrast,
      at this time point genes involved in phenoloxidase activation and cellular immune
      responses were globally down-regulated after parasitism in accordance with the
      observed inhibition of wasp egg encapsulation.

PMID- 25584518
TI  - Parental control, nurturance, self-efficacy, and screen viewing among 5- to 6
      year-old children: a cross-sectional mediation analysis to inform potential
      behavior change strategies.
AB  - BACKGROUND: Children's screen viewing (SV) is associated with higher levels of
      childhood obesity. Many children exceed the American Academy of Pediatrics
      guideline of 2 hours of television (TV) per day. There is limited information
      about how parenting styles and parental self-efficacy to limit child screen time
      are associated with children's SV. This study examined whether parenting styles
      were associated with the SV of young children and whether any effects were
      mediated by parental self-efficacy to limit screen time. METHODS: Data were from
      a cross-sectional survey conducted in 2013. Child and parent SV were reported by
      a parent, who also provided information about their parenting practices and self
      efficacy to restrict SV. A four-step regression method examined whether parenting
      styles were associated with the SV of young children. Mediation by parental self
      efficacy to limit screen time was examined using indirect effects. RESULTS: On a
      weekday, 90% of children watched TV for <2 hours per day, decreasing to 55% for
      boys and 58% for girls at weekends. At the weekend, 75% of children used a
      personal computer at home, compared with 61% during the week. Self-reported
      parental control, but not nurturance, was associated with children's TV viewing.
      Parental self-efficacy to limit screen time was independently associated with
      child weekday TV viewing and mediated associations between parental control and
      SV. CONCLUSIONS: Parental control was associated with lower levels of SV among 5-
      to 6-year-old children. This association was partially mediated by parental self
      efficacy to limit screen time. The development of strategies to increase parental
      self-efficacy to limit screen-time may be useful.

PMID- 25584520
TI  - Magnetic purification of curcumin from Curcuma longa rhizome by novel naked
      maghemite nanoparticles.
AB  - Naked maghemite nanoparticles, namely, surface active maghemite nanoparticles
      (SAMNs), characterized by a diameter of about 10 nm, possessing peculiar
      colloidal stability, surface chemistry, and superparamagnetism, present
      fundamental requisites for the development of effective magnetic purification
      processes for biomolecules in complex matrices. Polyphenolic molecules presenting
      functionalities with different proclivities toward iron chelation were studied as
      probes for testing SAMN suitability for magnetic purification. Thus, the binding
      efficiency and reversibility on SAMNs of phenolic compounds of interest in the
      pharmaceutical and food industries, namely, catechin, tyrosine, hydroxytyrosine,
      ferulic acid, coumaric acid, rosmarinic acid, naringenin, curcumin, and cyanidin
      3-glucoside, were evaluated. Curcumin emerged as an elective compound, suitable
      for magnetic purification by SAMNs from complex matrices. A combination of
      curcumin, demethoxycurcumin, and bis-demethoxycurcumin was recovered by a single
      magnetic purification step from extracts of Curcuma longa rhizomes, with a purity
      >98% and a purification yield of 45%, curcumin being >80% of the total purified
      curcuminoids. 

PMID- 25584522
TI  - Undesirable Enzymatic Browning in Crustaceans: Causative Effects and Its
      Inhibition by Phenolic Compounds.
AB  - Undesirable enzymatic browning mediated by polyphenol oxidase (E.C. 1.14.18.1) on
      the surface of seafood from crustaceans have been a great concern to food
      processors, causing quality losses of seafood products. Seafoods especially from
      crustaceans are worldwide consumed due to their delicacy and nutritional value.
      However, black spot formation (melanosis) is the major problem occurring in
      crustaceans during postmortem handling and refrigerated storage induce
      deleterious changes in organoleptic properties and, therefore, decreases
      commercial value. Polyphenoloxidase (PPO), the copper-containing metalloprotein
      involved in oxidation of phenol to quinone is the major biochemical reaction of
      melanosis formation. This enzymatic mechanism causes unappealing blackening in
      postharvest crustaceans. To alleviate the melanosis formation in crustaceans, use
      of phenolic compounds from plant extract can serve as antimelanotics and appears
      to be a good alternative to the conventional sulfites which are associated with
      health-related disorders. In this review, we focuses on the unique features about
      the structure, distribution, and properties of PPO as well as mechanism of
      melanosis formation and provide a comprehensive deeper insight on the factors
      affecting melanosis formation and its inhibition by various antimelanotics
      including newly discovered plant phenolic compounds. 

PMID- 25584523
TI  - An overview of operationalizing criteria for ME, ME/CFS, and CFS case
      definitions.

PMID- 25584521
TI  - Highly angiogenic peptide nanofibers.
AB  - Major limitations of current tissue regeneration approaches using artificial
      scaffolds are fibrous encapsulation, lack of host cellular infiltration, unwanted
      immune responses, surface degradation preceding biointegration, and artificial
      degradation byproducts. Specifically, for scaffolds larger than 200-500 MUm,
      implants must be accompanied by host angiogenesis in order to provide adequate
      nutrient/waste exchange in the newly forming tissue. In the current work, we
      design a peptide-based self-assembling nanofibrous hydrogel containing cell
      mediated degradation and proangiogenic moieties that specifically address these
      challenges. This hydrogel can be easily delivered by syringe, is rapidly
      infiltrated by cells of hematopoietic and mesenchymal origin, and rapidly forms
      an extremely robust mature vascular network. Scaffolds show no signs of fibrous
      encapsulation and after 3 weeks are resorbed into the native tissue. These
      supramolecular assemblies may prove a vital paradigm for tissue regeneration and
      specifically for ischemic tissue disease. 

PMID- 25584524
TI  - Measuring substantial reductions in activity.
AB  - The case definitions for Myalgic Encephalomyelitis/chronic fatigue syndrome
      (ME/CFS), ME, and CFS each include a disability criterion requiring substantial
      reductions in activity in order to meet diagnostic criteria. Difficulties have
      been encountered in defining and operationalizing the substantial reduction
      disability criterion within these various illness definitions. The present study
      sought to relate measures of past and current activities in several domains
      including the SF-36, an objective measure of activity (e.g., actigraphy), a self
      reported quality of life scale, and measures of symptom severity. Results of the
      study revealed that current work activities had the highest number of significant
      associations with domains such as the SF-36 subscales, actigraphy, and symptom
      scores. As an example, higher self-reported levels of current work activity were
      associated with better health. This suggests that current work related activities
      may provide a useful domain for helping operationalize the construct of
      substantial reductions in activity. 

PMID- 25584525
TI  - Problems in defining post-exertional malaise.
AB  - Post-exertional malaise (PEM) is a cardinal symptom of the illnesses referred to
      as Myalgic Encephalomyelitis (ME), Myalgic Encephalomyelitis/chronic fatigue
      syndrome (ME/CFS), and chronic fatigue syndrome (CFS). PEM is reported to occur
      in many of these patients, and with several criteria (e.g., ME and ME/CFS), this
      symptom is mandatory (Carruthers et al., 2003 , 2011 ). In the present study, 32
      participants diagnosed with CFS (Fukuda et al., 1994 ) were examined on their
      responses to self-report items that were developed to capture the characteristics
      and patterns of PEM. As shown in the results, the slight differences in wording
      for various items may affect whether one is determined to have PEM according to
      currently used self-report criteria to assess CFS. Better understanding of how
      this symptom is assessed might help improve the diagnostic reliability and
      validity of ME, ME/CFS, and CFS.

PMID- 25584526
TI  - Are stamina and fatigue polar opposites? A case study.
AB  - Most individuals with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS)
      (Carruthers et al., 2003 ), Myalgic Encephalomyelitis (ME) (Carruthers et al.,
      2011 ), and chronic fatigue syndrome (CFS) (Fukuda et al., 1994 ) indicate that
      they experience fatigue and sharp decreases in energy levels, which hinder the
      ability to engage in physical activities (Friedberg & Jason, 1998 ). However,
      there are some individuals who reduce activity engagement in order to avoid a
      worsening of symptoms; thus these individuals may endorse lower levels of
      fatigue. Accordingly, those with low levels of fatigue but low endurance/stamina
      might be inadvertently excluded from some criteria based on the fatigue
      requirement. The current study serves as an exploration of the relationship
      between fatigue and stamina and the effects of these constructs on illness
      symptomology and their implications for assessment and diagnosis. 

PMID- 25584527
TI  - Complications in operationalizing lifelong fatigue as an exclusionary criterion.
AB  - The case definitions for chronic fatigue syndrome (CFS) and chronic fatigue
      syndrome/Myalgic Encephalomyelitis (ME) stipulate that the experience of lifelong
      fatigue is an exclusionary criterion (Carruthers et al., 2003 ; Fukuda et al.,
      1994 ). This article examines the lifelong fatigue construct and identifies
      potential validity and reliability issues in using lifelong fatigue as an
      exclusionary condition. Participants in the current study completed the DePaul
      Symptom Questionnaire (Jason et al., 2010 ), and responses were examined to
      determine if they had experienced lifelong fatigue. This article discusses the
      extensive process that was needed to confidently discern which participants had
      or did not have lifelong fatigue. Using the most rigorous standards, few
      individuals were classified as having lifelong fatigue. In addition, those with
      and without lifelong fatigue had few significant differences in symptoms and
      functional areas. This article concludes with a recommendation that lifelong
      fatigue should no longer be used as an exclusionary criterion for CFS or ME/CFS. 

PMID- 25584528
TI  - An investigation of symptoms predating CFS onset.
AB  - The Fukuda et al. (1994) criteria for chronic fatigue syndrome (CFS) specifies
      that a symptom can only be included within a diagnosis if it is experienced
      concurrently or following the onset of fatigue. In order to investigate this
      issue, participants provided information on persisting symptoms (lasting greater
      than six months) and whether those symptoms occurred prior to, concurrently, or
      following the onset of their fatigue. More symptoms were experienced after the
      fatigue onset than prior to the fatigue onset; however, a considerable number of
      participants reported experiencing persisting symptoms prior to the onset of CFS.
      Particularly, rates of hay fever and asthma were higher prior to the illness.
      Investigating symptoms prior to the onset of the illness might provide
      investigators with ways to better understand the etiology of this illness.

PMID- 25584530
TI  - In situ catalytic synthesis of high-graphitized carbon-coated LiFePO4 nanoplates
      for superior Li-ion battery cathodes.
AB  - The low electronic conductivity and one-dimensional diffusion channel along the b
      axis for Li ions are two major obstacles to achieving high power density of
      LiFePO4 material. Coating carbon with excellent conductivity on the tailored
      LiFePO4 nanoparticles therefore plays an important role for efficient charge and
      mass transport within this material. We report here the in situ catalytic
      synthesis of high-graphitized carbon-coated LiFePO4 nanoplates with highly
      oriented (010) facets by introducing ferrocene as a catalyst during thermal
      treatment. The as-obtained material exhibits superior performances for Li-ion
      batteries at high rate (100 C) and low temperature (-20  degrees C), mainly
      because of fast electron transport through the graphitic carbon layer and
      efficient Li(+)-ion diffusion through the thin nanoplates. 

PMID- 25584529
TI  - Chronic fatigue syndrome versus sudden onset myalgic encephalomyelitis.
AB  - A revised sudden onset case definition for Myalgic Encephalomyelitis (ME) has
      been developed (Jason, Damrongvachiraphan, et al., 2012 ) based on past case
      definitions. In a prior study, Jason, Brown, and colleagues ( 2012 ) compared
      patients recruited using the 1994 case definition of chronic fatigue syndrome
      (CFS) to contrast those meeting criteria for the revised ME criteria. They found
      that this revised ME case definition identified patients with more functional
      impairments and physical, mental, and cognitive problems than those meeting the
      CFS criteria. The study by Jason, Brown, et al. ( 2012 ) only selected
      individuals who first met the CFS criteria, and it only relied on one Chicago
      based data set. The current study replicated this comparison with two distinct
      data sets with different case ascertainment methods. Results indicate that the ME
      criteria identified a group of patients with more functional disabilities as well
      as more severe post-exertional malaise symptoms.

PMID- 25584531
TI  - Poly (N-isopropylacrylamide)-co-(acrylic acid) microgel/Ag nanoparticle hybrids
      for the colorimetric sensing of H2O2.
AB  - Poly (N-isopropylacrylamide)-co-(acrylic acid) (pNIPAm-co-AAc) microgels composed
      of Ag nanoparticles (Ag NPs) have been synthesized and employed for the
      colorimetric sensing of H2O2. Each pNIPAm-co-AAc microgel, which exhibited a
      diameter of ~800 nm, contained multiple Ag NPs (diameter of ~5 nm), and solutions
      of these hybrid materials showed a UV-vis absorption band at ~400 nm. This is due
      to the excitation of the Ag NP surface plasmon. We go on to show that the
      intensity of this absorption band is dependent on the concentration of H2O2 in
      solution. Specifically, in the presence of H2O2 the magnitude of the absorption
      peak dramatically decreases in a linear fashion over the concentration range of
      0.30 to 3.00 MUM H2O2 (r(2) = 0.9918). We go on to show that the response is
      selective for H2O2 and can still function in complex mixtures, e.g., we showed
      that the response is still robust in milk samples. While Ag NPs themselves can
      exhibit similar responses, this system has many benefits including sample
      processing and long term stability - i.e., Ag NPs are destabilized in solutions
      of a certain pH, and aggregate readily. Our microgel/Ag NP hybrids have been
      shown to be extremely stable and are easily purified prior to use by simple
      centrifugation/washing protocols. This system is simple and straightforward to
      use, is low cost, and can be used in complex media, which makes it practical for
      analyzing complex biological and environmental samples. 

PMID- 25584540
TI  - [Not Available].

PMID- 25584533
TI  - Vascular alterations underlie developmental problems manifested in cloned cattle
      before or after birth.
AB  - Although assisted reproductive techniques are commonly applied in humans and
      animals, they are frequently associated with major developmental deficits and
      reduced viability. To explore abnormalities associated with cloning or nuclear
      transfer (NT) as the most invasive of these methods, we used a bovine model to
      characterize abnormalities. Detailed necropsy examinations were done on 13 calves
      that died soon after birth; in addition, we included data from embryos and
      fetuses (produced by NT) that terminated prematurely. Bovine clones that survived
      until the neonatal period differed quantitatively and qualitatively from in-vivo
      derived cattle. Although alterations affected a variety of organs (e.g. heart,
      lung and liver), there was a clear association with abberant vascular
      developmental during the early intrauterine phase. Therefore, we concluded that
      vascular problems were key alterations induced by cloning (presumably via
      epigenetic modifications). 

PMID- 25584549
TI  - [Not Available].

PMID- 25584552
TI  - [Not Available].

PMID- 25584532
TI  - Acquisition through horizontal gene transfer of plasmid pSMA198 by Streptococcus
      macedonicus ACA-DC 198 points towards the dairy origin of the species.
AB  - BACKGROUND: Streptococcus macedonicus is an intriguing streptococcal species
      whose most frequent source of isolation is fermented foods similarly to
      Streptococcus thermophilus. However, S. macedonicus is closely related to
      commensal opportunistic pathogens of the Streptococcus bovis/Streptococcus
      equinus complex. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the pSMA198 plasmid
      isolated from the dairy strain Streptococcus macedonicus ACA-DC 198 in order to
      provide novel clues about the main ecological niche of this bacterium. pSMA198
      belongs to the narrow host range pCI305/pWV02 family found primarily in
      lactococci and to the best of our knowledge it is the first such plasmid to be
      reported in streptococci. Comparative analysis of the pSMA198 sequence revealed a
      high degree of similarity with plasmids isolated from Lactococcus lactis strains
      deriving from milk or its products. Phylogenetic analysis of the pSMA198 Rep
      showed that the vast majority of closely related proteins derive from lactococcal
      dairy isolates. Additionally, cloning of the pSMA198 ori in L. lactis revealed a
      100% stability of replication over 100 generations. Both pSMA198 and the
      chromosome of S. macedonicus exhibit a high percentage of potential pseudogenes,
      indicating that they have co-evolved under the same gene decay processes. We
      identified chromosomal regions in S. macedonicus that may have originated from
      pSMA198, also supporting a long co-existence of the two replicons. pSMA198 was
      also found in divergent biotypes of S. macedonicus and in strains isolated from
      dispersed geographic locations (e.g. Greece and Switzerland) showing that
      pSMA198's acquisition is not a recent event. CONCLUSIONS/SIGNIFICANCE: Here we
      propose that S. macedonicus acquired plasmid pSMA198 from L. lactis via an
      ancestral genetic exchange event that took place most probably in milk or dairy
      products. We provide important evidence that point towards the dairy origin of
      this species.

PMID- 25584556
TI  - [Not Available].

PMID- 25584558
TI  - [Not Available].

PMID- 25584563
TI  - [Not Available].

PMID- 25584565
TI  - ?

PMID- 25584566
TI  - [Retrospective research requires better digital archiving].

PMID- 25584567
TI  - [SBU report "misses" persuasive evidence. Dietary supplements extends the life of
      malnourished elderly].

PMID- 25584570
TI  - [Ultrasound vs. CT in ureteral stones--Swedish procedures apply].

PMID- 25584571
TI  - [Congratulations, Lakartidningen--a spirited 110-year-old!].

PMID- 25584572
TI  - [Reply to Tommy Cederholm and co-authors--Dietary supplements for the oldest can
      be beneficial even if they do not increase survival].

PMID- 25584573
TI  - [Drug information under the magnifying glass: Too short "expiration date" a
      threat to patient safety].

PMID- 25584575
TI  - [Threatened language preservation also threatens medical safety].

PMID- 25584574
TI  - [Research assistant program attracts research interested in Gothenburg].

PMID- 25584576
TI  - [About sixty Armenians on the Amalfi Coast and other mobile mistakes].

PMID- 25584577
TI  - [Healthcare guarantee and follow-up responsibilities. Incompatible requirements].

PMID- 25584582
TI  - [Not Available].

PMID- 25584580
TI  - [Spontaneous intrauterine rupture of the umbilical cord is very uncommon but a
      serious condition].
AB  - Spontaneous intrauterine rupture of the umbilical cord is an uncommon and
      dangerous complication during delivery. We describe a case of a 27-year-old woman
      with a normal pregnancy. When the membranes broke, the fetal heart sounds
      suddenly disappeared, and the vaginal bleeding was heavier than normal. An
      emergency caesarean section was executed and the examination of the placenta
      revealed a broken umbilical artery. The child was born with an Apgar score of
      0,1,1 and a blood gas analysis from the umbilical vein showed pH 6.68 and Base
      Excess -24.3. Urgent treatment with heart massage, adrenaline, blood transfusion
      and tribonate was initiated and followed by therapeutic hypothermia. The child
      was discharged after 10 days with no pathological findings on a MRI examination
      of the brain. The 6 month follow-up showed a normal development. When a fetal
      bleeding is suspected, it is important to inform a neonatologist so that correct
      treatment can be started as early as possible. 

PMID- 25584583
TI  - [Not Available].
AB  - Psychiatric diagnoses are not reflections of the aetiology of the disorder, but
      rather lists of symptoms with considerable overlaps, which hamper research and
      may cause confusion. The diagnoses of autism spectrum disorder, attention deficit
      hyperactivity disorder and tic disorder are often comorbid along with a number of
      other symptomatic syndromes. Individual immune responsivity is possibly involved
      in pathophysiological mechanisms. Multiple environmental factors may contribute
      to the clinical phenotypes. Recent research supports to some extent the
      involvement of dietary and nutritional factors in ADHD. In spite of impressive
      progress in the molecular biological understanding of the pathophysiology of
      these disorders, treatment options are still limited and more research is
      warranted. 

PMID- 25584597
TI  - [Not Available].
AB  - Co-existence of attention-deficit/hyperactivity disorder, oppositional defiant
      disorder, tic disorders, developmental coordination disorder, language disorder,
      learning problems, and autism spectrum disorder and sharing of symptoms across
      disorders, contribute to the typical clinical presentation in child psychiatry as
      well as in developmen-tal medicine. The acronym ESSENCE refers to Early
      Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations.
      Affected children are brought for clinical assessment because of impairing
      symptoms that raise concern before the age of about 5 years in general
      development, communication and language, social inter-relatedness, motor
      coordination, attention, activity, behaviour, mood, and/or sleep. Such children
      are usually in need of a range of expert assessments, but a holistic approach is
      rarely taken from the start. Major problems in at least one ESSENCE domain before
      5 years of age predict poor mental health later in life. Expert ESSENCE centres
      for assessment, habilitation and treatment of these children are needed. 

PMID- 25584599
TI  - [Alcohol, drugs and tobacco smoking causes much of the burden of disease--Trends
      in Sweden 1990-2010 mapped based DALY method].
AB  - Various attempts have been made to measure the burden of alcohol, drugs and
      tobacco smoking on population health, and mortality is an often used measure. As
      part of the governmental strategy to prevent use of alcohol, drugs, doping and
      tobacco (ANDT) in Sweden, we assessed disease burden measured by DALY (Disability
      Adjusted Life Years), attributed to alcohol, drugs and tobacco over time, as an
      overall indicator of problem level. DALY was developed within the Global Burden
      of Disease study (GBD), and combines life lost to premature death (YLL) and years
      lived with disability (YLD) in one measure. In 2010 tobacco contributed to 7.7%
      of the total disease burden in Sweden, followed by alcohol (3.4%) and drugs
      (1.3%). The disease burden caused by tobacco has decreased substantially since
      1990, while small changes are observed for alcohol and drugs. Much of the disease
      burden specially related to drugs and alcohol was related to YLD, which can be
      captured with the DALY measure. 

PMID- 25584600
TI  - [The supervisor has a crucial role in the medical student's degree projects.
      Experiences from seven semesters at Karolinska Institutet].
AB  - In Sweden degree projects have a central role in evaluation of higher education,
      wherefore significant resources are spent on developing students' research
      competence. The undergraduate medical program at Karolinska Institutet introduced
      its degree project course in 2010. This paper gives an overview of the course and
      summarizes experiences from the first seven terms. In order to finalize their
      projects within one term, most students need substantial support. A highly
      structured course and frequent progress monitoring are advantageous. Other
      crucial factors are the quality of the supervision and students' verbal skills as
      well as support in scientific writing. In addition, increased awareness of the
      learning outcomes already at the beginning of the course may help students to
      achieve the expected results. Finally, students need to recognize their own
      responsibility for learning.  

PMID- 25584601
TI  - [Residual states in 30 percent of adult patients with Bell's palsy. Early
      treatment with cortisone improves the healing process].
AB  - Bell's palsy is an acute unilateral weakness or paralysis of the face of unknown
      cause. The incidence of the disease is 30 individuals per 100,000 per year. It is
      a diagnosis of exclusion and other known causes for acute peripheral facial palsy
      must be ruled out. The prognosis is overall favorable and about 70% of the
      patients recover completely within 6 months without treatment. Recent randomized
      controlled Bell's palsy trials have shown that treatment with corticosteroids
      shortens time to recovery and improves recovery rates while antiviral treatment
      alone is not more effective than placebo. The combination of corticosteroids and
      antivirals has not been proven more effective than corticosteroids alone. We
      present an update of Bell's palsy in adults with focus on diagnosis, treatment
      and follow-up of these patients. 

PMID- 25584602
TI  - [Identification of paroxysmal, transient arrhythmias: Intermittent registration
      more efficient than the 24-hour Holter monitoring].
AB  - Many patients suffer from palpitations or dizziness/presyncope. These patients
      are often referred for Holter ECG (24 hour), although the sensitivity for
      detecting arrhythmias is low. A new method, short intermittent regular and
      symptomatic ECG registrations at home, might be a convenient and more sensitive
      alternative also suitable for primary health care. In this case report we present
      a patient who had contacted health care several times during a seven year period
      for paroxysmal palpitations. Routine examination with 24 hour Holter ECG and
      event recorder did not result in a diagnosis. Using intermittent handheld ECG
      registration at home, a paroxysmal supraventricular arrhythmia was diagnosed.
      Further investigation revealed that the patient had a concealed Wolff-Parkinson
      White (WPW) syndrome. 

PMID- 25584603
TI  - ["We are here to give what we can to life, not to take what we can" - Sir William
      Osler - playful humanist and doctor with pediatric interest].

PMID- 25584605
TI  - [100-year-old who refused to be revived].

PMID- 25584606
TI  - [Adequate care or medical prostitution?--The National Audit Office's report
      should provide a shot in the back].

PMID- 25584607
TI  - [Value-based health care shifts the focus from care production to health].

PMID- 25584608
TI  - [The Swedish Society of Medicine: Value-based health care is loaded with
      problems, but also opportunities].

PMID- 25584609
TI  - [Speaking! Child abuse--do not violate the child online].

PMID- 25584610
TI  - [More with atrial fibrillation, anticoagulants since the coming of NOAK ].
AB  - Since the introduction of NOAC (non-vitamin K antagonist oral anticoagulants) in
      2011 as thromboprophylactic treatment for patients with atrial fibrillation, AF,
      the number of patients with a diagnosis of atrial fibrillation has increased
      markedly in our health care registers. The proportion of patients treated with
      warfarin or NOAC has increased from 47 % to 58 % in 2013. The use of
      acetylsalicylic acid in patients is decreasing rapidly in patients with AF. NOAC
      are mostly prescribed by specialists and are mainly used in younger patients with
      lower CHA2DS2-VASc scores and lower risk for renal insufficiency and bleeding. 

PMID- 25584611
TI  - Cadmium transporters in the kidney and cadmium-induced nephrotoxicity.
AB  - Among the organs in which the environmental pollutant cadmium causes toxicity,
      the kidney has gained the most attention in recent years. Numerous studies have
      sought to unravel the exact pathways by which cadmium enters the renal epithelial
      cells and the mechanisms by which it causes toxicity in the kidney. The purpose
      of this review is to present the progress made on the mechanisms of cadmium
      transport in the kidney and the role of transporter proteins in cadmium-induced
      nephrotoxicity. 

PMID- 25584612
TI  - Hair dyes resorcinol and lawsone reduce production of melanin in melanoma cells
      by tyrosinase activity inhibition and decreasing tyrosinase and microphthalmia
      associated transcription factor (MITF) expression.
AB  - Hair coloring products are one of the most important cosmetics for modern people;
      there are three major types of hair dyes, including the temporary, semi-permanent
      and permanent hair dyes. The selected hair dyes (such as ammonium persulfate,
      sodium persulfate, resorcinol and lawsone) are the important components for hair
      coloring products. Therefore, we analyzed the effects of these compounds on
      melanogenesis in B16-F10 melanoma cells. The results proved that hair dyes
      resorcinol and lawsone can reduce the production of melanin. The results also
      confirmed that resorcinol and lawsone inhibit mushroom and cellular tyrosinase
      activities in vitro. Resorcinol and lawsone can also downregulate the protein
      levels of tyrosinase and microphthalmia-associated transcription factor (MITF) in
      B16-F10 cells. Thus, we suggest that frequent use of hair dyes may have the risk
      of reducing natural melanin production in hair follicles. Moreover, resorcinol
      and lawsone may also be used as hypopigmenting agents to food, agricultural and
      cosmetic industry in the future. 

PMID- 25584613
TI  - Membrane trafficking in the yeast Saccharomyces cerevisiae model.
AB  - The yeast Saccharomyces cerevisiae is one of the best characterized eukaryotic
      models. The secretory pathway was the first trafficking pathway clearly
      understood mainly thanks to the work done in the laboratory of Randy Schekman in
      the 1980s. They have isolated yeast sec mutants unable to secrete an
      extracellular enzyme and these SEC genes were identified as encoding key
      effectors of the secretory machinery. For this work, the 2013 Nobel Prize in
      Physiology and Medicine has been awarded to Randy Schekman; the prize is shared
      with James Rothman and Thomas Sudhof. Here, we present the different trafficking
      pathways of yeast S. cerevisiae. At the Golgi apparatus newly synthesized
      proteins are sorted between those transported to the plasma membrane (PM), or the
      external medium, via the exocytosis or secretory pathway (SEC), and those
      targeted to the vacuole either through endosomes (vacuolar protein sorting or VPS
      pathway) or directly (alkaline phosphatase or ALP pathway). Plasma membrane
      proteins can be internalized by endocytosis (END) and transported to endosomes
      where they are sorted between those targeted for vacuolar degradation and those
      redirected to the Golgi (recycling or RCY pathway). Studies in yeast S.
      cerevisiae allowed the identification of most of the known effectors, protein
      complexes, and trafficking pathways in eukaryotic cells, and most of them are
      conserved among eukaryotes. 

PMID- 25584614
TI  - Relationship between expression of onco-related miRNAs and the endoscopic
      appearance of colorectal tumors.
AB  - Accumulating data indicates that certain microRNAs (miRNAs or miRs) are
      differently expressed in samples of tumors and paired non-tumorous samples taken
      from the same patients with colorectal tumors. We examined the expression of onco
      related miRNAs in 131 sporadic exophytic adenomas or early cancers and in 52
      sporadic flat elevated adenomas or early cancers to clarify the relationship
      between the expression of the miRNAs and the endoscopic morphological appearance
      of the colorectal tumors. The expression levels of miR-143, -145, and -34a were
      significantly reduced in most of the exophytic tumors compared with those in the
      flat elevated ones. In type 2 cancers, the miRNA expression profile was very
      similar to that of the exophytic tumors. The expression levels of miR-7 and -21
      were significantly up-regulated in some flat elevated adenomas compared with
      those in exophytic adenomas. In contrast, in most of the miR-143 and -145 down
      regulated cases of the adenoma-carcinoma sequence and in some of the de novo
      types of carcinoma, the up-regulation of oncogenic miR-7 and/or -21 contributed
      to the triggering mechanism leading to the carcinogenetic process. These findings
      indicated that the expression of onco-related miRNA was associated with the
      morphological appearance of colorectal tumors. 

PMID- 25584617
TI  - Psoriatic arthritis - expanding options, exciting times?

PMID- 25584616
TI  - Rapid and sensitive identification of the herbal tea ingredient Taraxacum
      formosanum using loop-mediated isothermal amplification.
AB  - Taraxacum formosanum (TF) is a medicinal plant used as an important component of
      health drinks in Taiwan. In this study, a rapid, sensitive and specific loop
      mediated isothermal amplification (LAMP) assay for authenticating TF was
      established. A set of four specific LAMP primers was designed based on the
      nucleotide sequence of the internal transcribed spacer 2 (ITS2) nuclear ribosomal
      DNA (nrDNA) of TF. LAMP amplicons were successfully amplified and detected when
      purified genomic DNA of TF was added in the LAMP reaction under isothermal
      condition (65  degrees C) within 45 min. These specific LAMP primers have high
      specificity and can accurately discriminate Taraxacum formosanum from other
      adulterant plants; 1 pg of genomic DNA was determined to be the detection limit
      of the LAMP assay. In conclusion, using this novel approach, TF and its misused
      plant samples obtained from herbal tea markets were easily identified and
      discriminated by LAMP assay for quality control. 

PMID- 25584615
TI  - Defective autophagosome formation in p53-null colorectal cancer reinforces crocin
      induced apoptosis.
AB  - Crocin, a bioactive molecule of saffron, inhibited proliferation of both HCT116
      wild-type and HCT116 p53(-/-) cell lines at a concentration of 10 mM. Flow
      cytometric analysis of cell cycle distribution revealed that there was an
      accumulation of HCT116 wild-type cells in G1 (55.9%, 56.1%) compared to the
      control (30.4%) after 24 and 48 h of crocin treatment, respectively. However,
      crocin induced only mild G2 arrest in HCT116 p53(-/-) after 24 h. Crocin induced
      inefficient autophagy in HCT116 p53(-/-) cells, where crocin induced the
      formation of LC3-II, which was combined with a decrease in the protein levels of
      Beclin 1 and Atg7 and no clear p62 degradation. Autophagosome formation was not
      detected in HCT116 p53(-/-) after crocin treatment predicting a nonfunctional
      autophagosome formation. There was a significant increase of p62 after treating
      the cells with Bafilomycin A1 (Baf) and crocin compared to crocin exposure alone.
      Annexin V staining showed that Baf-pretreatment enhanced the induction of
      apoptosis in HCT116 wild-type cells. Baf-exposed HCT116 p53(-/-) cells did not,
      however, show any enhancement of apoptosis induction despite an increase in the
      DNA damage-sensor accumulation, gammaH2AX indicating that crocin induced an
      autophagy-independent classical programmed cell death.

PMID- 25584618
TI  - Paediatric rheumatology: where are we going?

PMID- 25584619
TI  - SARCOSPA - Sarcopenia in spondyloarthritis patients.
AB  - INTRODUCTION: The loss of muscle mass (MM) is a serious problem which has been
      demonstrated in patients with rheumatoid arthritis. There are few studies about
      the loss of MM in patients with spondyloarthritis (Spa). OBJECTIVE: To assess
      muscle mass index (MMI) in a cohort of patients with Spa and compare it with a
      control group of healthy individuals; to verify if a higher risk of sarcopenia is
      related with disease activity, functional impairment, duration of the illness and
      radiological damage. METHODS: Case control study. Muscle mass index (MMI) was
      determined, from the value of MM, using Lee's equation, in a cohort of patients
      with spondyloarthritis and in a control group. Bath Ankylosing Spondylitis
      Disease Activity and Function Indexes (BASDAI and BASFI), Ankylosing Spondylitis
      Quality of Life (ASQoL) and Modified Stoke Ankylosing Spondylitis Spinal Score
      (mSASSS) were assessed in a cohort of patients with axial Spa, as well as Health
      Assessment Questionnaire (HAQ) and Disease Activity Score 28 (DAS28) in patients
      with peripheral disease. Data were treated using SPSS version 17.0. Values of
      p<0,05 were considered with statistical significance. RESULTS: 60 patients were
      enrolled; 48.2% were males, mean age 45.5+/-13.4 years, mean disease duration
      10.9+/-11.6 years; 36 had ankylosing spondylitis and 24 had psoriatic arthritis.
      62% of patients had sarcopenia and there was a significant difference in mean MMI
      between patients and controls (7.65+/-0.98 vs 8.25+/-0.92; p=0.001, OR =5.23. In
      male patients, there was a statistically significant moderate negative
      correlation between MMI and BASDAI and BASFI (p=-0.536 and p=-0.445). No other
      significant correlations were identified. CONCLUSION: Our study supports the
      hypothesis of a greater prevalence of sarcopenia in patients with Spa compared to
      healthy controls. Some limitations included the sample size, potential
      confounding factor such the bias of measurement and the use of a non-validated
      equation to Portuguese population to calculate MM.

PMID- 25584620
TI  - [Psoriatic Arthritis concomitant with Paget's Disease - a case report].
AB  - Paget disease of bone is a focal disorder of bone metabolism; it is characterized
      by an accelerated rate of bone remodeling, with profound changes in the bone
      structure, making it fragile. This condition affects approximately 2% to 5% of
      the population older than 40. The main clinical manifestations of Paget's disease
      are pain and bone deformity, although the majority of patients are asymptomatic.
      Psoriatic Arthritis is a spondyloarthritis with a prevalence of about 0,1%. It is
      characterized by the presence of arthritis, enthesitis and/or dactylitis
      associated with a familiar or personal history of psoriasis. Several clinical
      patterns of joint involvement in psoriatic arthritis have been identified,
      namely, the polyarticular pattern, similar to rheumatoid arthritis. Arthritis
      precedes skin disease in approximately 13 to 17 % of the cases. The authors
      report a clinical case of a 60 years old patient with polyarthritis and
      dactylitis who was diagnosed with psoriatic arthritis and Paget's disease of
      bone. The concomitance of the two entities, in the same individual, with so
      different pathogenesis and clinical features, have never been described on
      literature. Because of the complexity on the clinical and imaging evaluation as
      the result of the coexistence of both pathologies, the authors consider relevant
      to publish this singular case. 

PMID- 25584621
TI  - Ocular and parotid sarcoidosis - panda sign.
AB  - Sarcoidosis is a multisystem disease with ocular involvement in 25-50% of
      patients, parotid and other salivary glands involvement in 6%, resulting in this
      characteristic panda sign in Gallium-67 scan, present in a 16 year old male with
      a history of bilateral recurrent uveitis. 

PMID- 25584622
TI  - A rare cause of chronic hip pain: Intraarticular synovial chondromatosis.

PMID- 25584623
TI  - Brucellosis in spondyloarthritis mimicking an exacerbation.
AB  - Spondyloarthritis are a group of chronic inflammatory diseases that affect the
      axial skeleton, entheses and peripheral joints and may have extraarticular
      manifestations such as uveitis, psoriasis and inflammatory bowel disease.
      Brucellosis is a systemic infectious disease, endemic in Middle East, Latin
      America, and Mediterranean countries, which may present manifestations that
      resemble other diseases posing serious problems of differential diagnosis. Some
      hallmarks of Brucellosis may mimic a spondyloarthritis flare. In this paper,
      authors present a clinical case of brucellosis occurring in a patient with
      spondyloarthritis. Clinical symptoms initially mimicked exacerbation of
      spondyloarthritis. 

PMID- 25584624
TI  - FloTrac(r) monitoring system: what are its uses in critically ill medical
      patients?
AB  - The FloTrac(r)/Vigileo device uses arterial pressure waveform analysis to
      calculate stroke volume and cardiac output; it does not require calibration
      against an independent measurement of cardiac output. Consequently, it provides a
      method to determine hemodynamic status, changes in the clinical course and
      responses to therapeutic interventions in patients who have arterial catheters in
      place. These devices perform relatively well in stable patients undergoing
      surgery and having an acceptable percentage error in differences between the
      FloTrac(r) device and invasive monitoring using pulmonary catheters. However, in
      patients with septic shock and other clinical states associated with low systemic
      vascular resistances, such as cirrhosis, the FloTrac(r) does not provided
      acceptable correlation with independent measurements with pulmonary artery
      catheters. FloTrac(r) measurements often underestimate the cardiac output and
      have unacceptably high percent error, which ranges from 30% to 60%. There is a
      moderate correlation with changes in cardiac output after fluid administration,
      but a poor correlation with changes in cardiac output after increases or
      decreases in norepinephrine administration. The bias between measurements
      increases as the systemic vascular resistance decreases. Consequently, cardiac
      output measurements using the FloTrac(r) device are not accurate enough for use
      in patients with septic shock, advanced liver disease and other medical
      conditions associated with decreased vascular tone. 

PMID- 25584626
TI  - The internal plumbing of algal chloroplasts.
AB  - High-resolution images of chloroplast structure in the alga Chlamydomonas offer
      new insights into photosynthesis. 

PMID- 25584627
TI  - Photonic effects on the radiative decay rate and luminescence quantum yield of
      doped nanocrystals.
AB  - Nanocrystals (NCs) doped with luminescent ions form an emerging class of
      materials. In contrast to excitonic transitions in semiconductor NCs, the optical
      transitions are localized and not affected by quantum confinement. The radiative
      decay rates of the dopant emission in NCs are nevertheless different from their
      bulk analogues due to photonic effects, and also the luminescence quantum yield
      (QY, important for applications) is affected. In the past, different theoretical
      models have been proposed to describe the photonic effects for dopant emission in
      NCs, with little experimental validation. In this work we investigate the
      photonic effects on the radiative decay rate of luminescent doped NCs using 4 nm
      LaPO4 NCs doped with Ce(3+) or Tb(3+) ions in different refractive index solvents
      and bulk crystals. We demonstrate that the measured influence of the refractive
      index on the radiative decay rate of the Ce(3+) emission, having near unity QY,
      is in excellent agreement with the theoretical nanocrystal-cavity model.
      Furthermore, we show how the nanocrystal-cavity model can be used to quantify the
      nonunity QY of Tb(3+)-doped LaPO4 NCs and demonstrate that, as a general rule,
      the QY is higher in media with higher refractive index. 

PMID- 25584628
TI  - High-resolution assessment of land use impacts on biodiversity in life cycle
      assessment using species habitat suitability models.
AB  - Agricultural land use is a main driver of global biodiversity loss. The
      assessment of land use impacts in decision-support tools such as life cycle
      assessment (LCA) requires spatially explicit models, but existing approaches are
      either not spatially differentiated or modeled at very coarse scales (e.g.,
      biomes or ecoregions). In this paper, we develop a high-resolution (900 m)
      assessment method for land use impacts on biodiversity based on habitat
      suitability models (HSM) of mammal species. This method considers potential land
      use effects on individual species, and impacts are weighted by the species'
      conservation status and global rarity. We illustrate the method using a case
      study of crop production in East Africa, but the underlying HSMs developed by the
      Global Mammals Assessment are available globally. We calculate impacts of three
      major export crops and compare the results to two previously developed methods
      (focusing on local and regional impacts, respectively) to assess the relevance of
      the methodological innovations proposed in this paper. The results highlight
      hotspots of product-related biodiversity impacts that help characterize the links
      among agricultural production, consumption, and biodiversity loss. 

PMID- 25584629
TI  - Solvent composition dictates emergence in dynamic molecular networks containing
      competing replicators.
AB  - In Darwinian evolution, species that are better adapted to their environment win
      the competition for common resources from less well-adapted competitors. Thus, in
      such scenarios the nature of the environment may dictate the outcome of the
      competition. We investigated to what degree these biological principles acting at
      the level of species extend to the molecular level into systems based on fully
      synthetic self-replicating molecules. We now report two systems in which two
      replicators compete for a common building block and where the environment
      dictates which of the two replicators wins. We observed that subtle changes in
      the environment can lead to dramatic differences in the outcome of the
      competition. 

PMID- 25584625
TI  - Native architecture of the Chlamydomonas chloroplast revealed by in situ cryo
      electron tomography.
AB  - Chloroplast function is orchestrated by the organelle's intricate architecture.
      By combining cryo-focused ion beam milling of vitreous Chlamydomonas cells with
      cryo-electron tomography, we acquired three-dimensional structures of the
      chloroplast in its native state within the cell. Chloroplast envelope inner
      membrane invaginations were frequently found in close association with thylakoid
      tips, and the tips of multiple thylakoid stacks converged at dynamic sites on the
      chloroplast envelope, implicating lipid transport in thylakoid biogenesis.
      Subtomogram averaging and nearest neighbor analysis revealed that RuBisCO
      complexes were hexagonally packed within the pyrenoid, with ~15 nm between their
      centers. Thylakoid stacks and the pyrenoid were connected by cylindrical pyrenoid
      tubules, physically bridging the sites of light-dependent photosynthesis and
      light-independent carbon fixation. Multiple parallel minitubules were bundled
      within each pyrenoid tubule, possibly serving as conduits for the targeted one
      dimensional diffusion of small molecules such as ATP and sugars between the
      chloroplast stroma and the pyrenoid matrix.

PMID- 25584631
TI  - Assessment of several DFT functionals in calculation of the reduction potentials
      for Ni-, Pd-, and Pt-bis-ethylene-1,2-dithiolene and -diselenolene complexes.
AB  - We performed an assessment of 10 common DFT functionals to determine their
      suitability for calculating the reduction potentials of the
      ([M(S2C2H2)2](0)/[M(S2C2H2)2](1-)), ([M(Se2C2H2)2](0)/[M(Se2C2H2)2](1-)),
      ([M(S2C2H2)2](1-)/[M(S2C2H2)2](2-)), and ([M(Se2C2H2)2](1-)/[M(Se2C2H2)2](2-))
      redox couples (M = Ni, Pd, and Pt). Overall it was found that the M06 functional
      leads to the best agreement with the gold standard CCSD(T) method with an average
      difference of only +0.07 V and a RMS of 0.07 V in calculated reduction
      potentials. The variability in calculated reduction potentials between the
      various DFT functionals arise, in part, from the multireference character of
      these systems, which was determined by the T1 diagnostic values. Thus, the
      bisdiselenolene complexes show similar multireference character as the
      bisdithiolene complexes, which were previously shown to have such character. In
      particular, for the Ni-, Pd-, and Pt-bisdiselenolene complexes the average T1
      values are 0.05, 0.03, and 0.02, respectively. For the CCSD(T) calculations the
      similarities in the reduction potentials between analogous bisdithiolene and
      bisdiselenolene redox couples, which appear to be independent of the metal, is a
      result of the noninnocence of the dithiolene and diselenolene ligands. Thus, the
      reduction potential is more dependent on the ligand than the metal. 

PMID- 25584632
TI  - Synthesis of gem-difluoromethylenated polycyclic cage compounds.
AB  - The synthesis of gem-difluoromethylenated polycyclic cage compounds, utilizing
      PhSCF2SiMe3 as a gem-difluoromethylene building block, is described. The fluoride
      catalyzed nucleophilic addition of PhSCF2SiMe3 to both maleic anhydride
      cyclopentadiene and maleic anhydride-cyclohexadiene adducts was accomplished with
      high stereoselectivity to provide the corresponding adducts that were treated
      with Grignard reagents, followed by acid-catalyzed lactonization to afford the
      corresponding gamma-butyrolactones, each as a single isomer. These gamma
      butyrolactones underwent intramolecular radical cyclization to give the
      corresponding tetracyclic cage gamma-butyrolactones, which were employed as
      precursors for the synthesis of gem-difluoromethylenated tetracyclic cage lactols
      or tetracyclic cage furans, upon treatment with Grignard reagents. 

PMID- 25584633
TI  - Nickel-catalyzed alkynylation of anisoles via C-O bond cleavage.
AB  - A new cross-coupling reaction has been developed for the introduction of an
      alkyne moiety to an anisole derivative through C-O bond activation using an NHC
      ligand. This method has been used for direct alkynylation of a broad range of
      anisole derivatives and provided rapid access to compounds with potential
      applications in biological and materials science. 

PMID- 25584630
TI  - Function-oriented development of CXCR4 antagonists as selective human
      immunodeficiency virus (HIV)-1 entry inhibitors.
AB  - Motivated by the pivotal role of CXCR4 as an HIV entry co-receptor, we herein
      report a de novo hit-to-lead effort on the identification of subnanomolar purine
      based CXCR4 antagonists against HIV-1 infection. Compound 24, with an EC50 of 0.5
      nM against HIV-1 entry into host cells and an IC50 of 16.4 nM for inhibition of
      radioligand stromal-derived factor-1alpha (SDF-1alpha) binding to CXCR4, was also
      found to be highly selective against closely related chemokine receptors. We
      rationalized that compound 24 complementarily interacted with the critical CXCR4
      residues that are essential for binding to HIV-1 gp120 V3 loop and subsequent
      viral entry. Compound 24 showed a 130-fold increase in anti-HIV activity compared
      to that of the marketed CXCR4 antagonist, AMD3100 (Plerixafor), whereas both
      compounds exhibited similar potency in mobilization of CXCR4(+)/CD34(+) stem
      cells at a high dose. Our study offers insight into the design of anti-HIV
      therapeutics devoid of major interference with SDF-1alpha function. 

PMID- 25584635
TI  - Tellurium speciation, connectivity, and chemical order in As(x)Te(100-x) glasses:
      results from two-dimensional 125Te NMR spectroscopy.
AB  - The short-range structure, connectivity, and chemical order in As(x)Te(100-x) (25
      <= x <= 65) glasses are studied using high-resolution two-dimensional projection
      magic-angle-turning (pjMAT) (125)Te nuclear magnetic resonance (NMR)
      spectroscopy. The (125)Te pjMAT NMR results indicate that the coordination of Te
      atoms obeys the 8-N coordination rule over the entire composition range. However,
      in strong contrast with the analogous glass-forming As-S and As-Se chalcogenides,
      significant violation of chemical order is observed in As-Te glasses over the
      entire composition range in the form of homopolar As-As (Te-Te) bonds, even in
      severely As (Te)-deficient glasses. The speciation of the Te coordination
      environments can be explained with the dissociation reaction model As2Te3 -> 2As
      + 3Te(II), characterized by a dissociation constant that is independent of glass
      composition. These structural characteristics can be attributed to the high
      metallicity of Te and the strong energetic similarity between the Te-Te, Te-As,
      and As-As bonds, and they are consistent with the monotonic and often nearly
      linear variation of physical properties observed in telluride glasses as a
      function of the Te content.

PMID- 25584634
TI  - Hybrid lipid-capped mesoporous silica for stimuli-responsive drug release and
      overcoming multidrug resistance.
AB  - Multidrug resistance (MDR) is known to be a great obstruction to successful
      chemotherapy, and considerable efforts have been devoted to reverse MDR including
      designing various functional drug delivery systems. In this study, hybrid lipid
      capped mesoporous silica nanoparticles (LTMSNs), aimed toward achieving stimuli
      responsive drug release to circumvent MDR, were specially designated for drug
      delivery. After modifying MSNs with hydrophobic chains through disulfide bond on
      the surface, lipid molecules composing polymer d-alpha-tocopherol polyethylene
      glycol 1000 succinate (TPGS) with molar ratio of 5:1 were subsequently added to
      self-assemble into a surrounded lipid layer via hydrophobic interaction acting as
      smart valves to block the pore channels of carrier. The obtained LTMSNs had a
      narrow size distribution of ca. 190 nm and can be stably dispersed in body
      fluids, which may ensure a long circulating time and ideal enhanced permeability
      and retention effect. Doxorubicin (DOX) was chosen as a model drug to be
      encapsulated into LTMSNs. Results showed that this hybrid lipid-capped mesoporous
      silica drug delivery system can achieve redox and pH-responsive release of DOX,
      thereby avoiding the premature leakage of drug before reaching the specific site
      and releasing DOX within the cancerous cells. Owing to the presence of TPGS
      containing lipid layer, LTMSNs-DOX exhibited higher uptake efficiency,
      cytotoxicity, and increased intracellular accumulation in resistant MCF-7/Adr
      cells compared with DOX solution, proving to be a promising vehicle to realize
      intracellular drug release and inhibit drug efflux. 

PMID- 25584636
TI  - Enhancing second harmonic generation in gold nanoring resonators filled with
      lithium niobate.
AB  - Plasmonic nanorings provide the unique advantage of a pronounced plasmonic field
      enhancement inside their core. If filled with a polarizable medium, it may
      significantly enhance its optical effects. Here, we demonstrate this proposition
      by filling gold nanorings with lithium niobate. The generated second harmonic
      signal is compared to the signal originating from an unpatterned lithium niobate
      surface. Measurements and simulation confirm an enhancement of about 20.
      Applications requiring nanoscopic localized light sources like fluorescence
      spectroscopy or quantum communication will benefit from our findings. 

PMID- 25584638
TI  - Genetic parameters for milk mineral content and acidity predicted by mid-infrared
      spectroscopy in Holstein-Friesian cows.
AB  - The aim of the present study was to estimate genetic parameters for calcium (Ca),
      phosphorus (P) and titratable acidity (TA) in bovine milk predicted by mid-IR
      spectroscopy (MIRS). Data consisted of 2458 Italian Holstein-Friesian cows
      sampled once in 220 farms. Information per sample on protein and fat percentage,
      pH and somatic cell count, as well as test-day milk yield, was also available.
      (Co)variance components were estimated using univariate and bivariate animal
      linear mixed models. Fixed effects considered in the analyses were herd of
      sampling, parity, lactation stage and a two-way interaction between parity and
      lactation stage; an additive genetic and residual term were included in the
      models as random effects. Estimates of heritability for Ca, P and TA were 0.10,
      0.12 and 0.26, respectively. Positive moderate to strong phenotypic correlations
      (0.33 to 0.82) existed between Ca, P and TA, whereas phenotypic weak to moderate
      correlations (0.00 to 0.45) existed between these traits with both milk quality
      and yield. Moderate to strong genetic correlations (0.28 to 0.92) existed between
      Ca, P and TA, and between these predicted traits with both fat and protein
      percentage (0.35 to 0.91). The existence of heritable genetic variation for Ca, P
      and TA, coupled with the potential to predict these components for routine cow
      milk testing, imply that genetic gain in these traits is indeed possible. 

PMID- 25584637
TI  - Oxidation of p53 through DNA charge transport involves a network of disulfides
      within the DNA-binding domain.
AB  - Transcription factor p53 plays a critical role in the cellular response to stress
      stimuli. We have seen that p53 dissociates selectively from various promoter
      sites as a result of oxidation at long-range through DNA-mediated charge
      transport (CT). Here, we examine this chemical oxidation and determine the
      residues in p53 that are essential for oxidative dissociation, focusing on the
      network of cysteine residues adjacent to the DNA-binding site. Of the eight
      mutants studied, only the C275S mutation shows decreased affinity for the Gadd45
      promoter site. However, both mutations C275S and C277S result in substantial
      attenuation of oxidative dissociation, with C275S causing the most severe
      attenuation. Differential thiol labeling was used to determine the oxidation
      states of cysteine residues within p53 after DNA-mediated oxidation. Reduced
      cysteines were iodoacetamide-labeled, whereas oxidized cysteines participating in
      disulfide bonds were (13)C2D2-iodoacetamide-labeled. Intensities of respective
      iodoacetamide-modified peptide fragments were analyzed by mass spectrometry. A
      distinct shift in peptide labeling toward (13)C2D2-iodoacetamide-labeled
      cysteines is observed in oxidized samples, confirming that chemical oxidation of
      p53 occurs at long range. All observable cysteine residues trend toward the heavy
      label under conditions of DNA CT, indicating the formation of multiple disulfide
      bonds among the cysteine network. On the basis of these data, it is proposed that
      disulfide formation involving C275 is critical for inducing oxidative
      dissociation of p53 from DNA. 

PMID- 25584640
TI  - Influence of oak maturation regimen on composition, sensory properties, quality,
      and consumer acceptability of cabernet sauvignon wines.
AB  - Oak barrels have long been the preferred method for oak maturation of wine, but
      barrels contribute significantly to production costs, so alternate oak maturation
      regimens have been introduced, particularly for wines at lower price points. To
      date, few studies have investigated consumers' acceptance of wines made using non
      traditional oak treatments. In this study, two Cabernet Sauvignon wines were aged
      using traditional (i.e., barrel) and/or alternative (i.e., stainless steel or
      plastic tanks and vats, with oak wood added) maturation regimens. Chemical and
      sensory analyses were subsequently performed to determine the influence on wine
      composition and sensory properties, that is, the presence of key oak-derived
      volatile compounds and perceptible oak aromas and flavor. The quality of a subset
      of wines was rated by a panel of 10 wine experts using a 20-point scoring system,
      with all wines considered technically sound. Consumer acceptance of wines was
      also determined. Hedonic ratings ranged from 5.7 to 5.9 (on a 9-point scale),
      indicating there was no significant difference in consumers' overall liking of
      each wine. However, segmentation based on individual liking scores identified
      three distinct clusters comprising consumers with considerably different wine
      preferences. These results justify wine producers' use of alternative oak
      maturation regimens to achieve wine styles that appeal to different segments of
      their target market.

PMID- 25584641
TI  - An organocatalytic biomimetic approach to alpha-aminophosphonates.
AB  - A novel biomimetic approach to optically active alpha-aminophosphonates utilizing
      readily available acylphosphonates and 2-chlorobenzylamine as starting materials
      has been described. The enantioselective protonation constitutes the main
      enantiodifferentiating step in the developed strategy. This nature-inspired
      approach proceeds efficiently and in a highly stereoselective manner. 

PMID- 25584639
TI  - Functions of double-stranded RNA-binding domains in nucleocytoplasmic transport.
AB  - The double-stranded RNA-binding domain (dsRBD) is a small protein domain found in
      eukaryotic, prokaryotic and viral proteins, whose central property is to bind to
      double-stranded RNA (dsRNA). Aside from this major function, recent examples of
      dsRBDs involved in the regulation of the sub-cellular localization of proteins,
      suggest that the participation of dsRBDs in nucleocytoplasmic trafficking is
      likely to represent a widespread auxiliary function of this type of RNA-binding
      domain. Overall, dsRBDs from proteins involved in many different biological
      processes have been reported to be implicated in nuclear import and export, as
      well as cytoplasmic, nuclear and nucleolar retention. Interestingly, the function
      of dsRBDs in nucleocytoplasmic trafficking is often regulated by their dsRNA
      binding capacity, which can either enhance or impair the transport from one
      compartment to another. Here, we present and discuss the emerging function of
      dsRBDs in nucleocytoplasmic transport. 

PMID- 25584642
TI  - Voltammetric study of the boric acid-salicylaldehyde-H-acid ternary system and
      its application to the voltammetric determination of boron.
AB  - The ternary system of boric acid, salicylaldehyde (SA) and H-acid (HA) was
      voltammetrically studied from kinetic and equilibrium points of view. The effect
      of the SA substituents was also studied by using two analogs, 5
      fluorosalicylaldehyde (F-SA) and 5-methylsalicylaldehyde (Me-SA). The three
      cathodic peaks of Azomethine H (AzH), Azomethine H-boric acid complex (AzB), and
      free SA were observed in the solution containing boric acid, SA and HA. The peak
      potentials of AzH and SA were shifted to negative potentials with increasing pH,
      while the peak potential of AzB was pH-independent. This difference indicates
      that a proton participates in the charge-transfer steps of the AzH and SA
      reductions, but not in that of the AzB reduction. The formation constants for the
      AzB complexation were similar among all the examined analogs. In the kinetic
      study, the reaction rate was higher in an acidic condition for the AzH formation,
      but in a neutral condition for the AzB formation. The rate constants for the AzB
      complexes were in the order of F-SA > SA ~ Me-SA, indicating that the fluoro
      group accelerates the F-AzB complexation. The AzB complexation mechanism is
      considered to consist of more than three steps, i.e., the pre-equilibrium of the
      salicylaldehyde-boric acid complex (SA-B) formation, the nucleophilic attack of
      HA on SA-B, and the remaining some steps to form AzB. Based on these results, the
      voltammetric determination method of boron using F-SA was optimized, which
      allowed the boron concentration to be determined within only 5 min with a 0.03 mg
      B dm(-3) detection limit. 

PMID- 25584655
TI  - Loss of the preferential control over the striato-nigral direct pathway by
      striatal NMDA receptors in a rat model of Parkinson's disease.
AB  - By using multi-probe microdialysis we previously demonstrated that endogenous
      glutamate differentially regulates the activity of the striatal output pathways
      in vivo, through N-methyl-d-aspartate (NMDA) receptors containing the GluN2A or
      GluN2B subunits. Using the same approach, we presently investigate whether
      reverse dialysis of NMDA in the striatum differentially affects GABA release in
      the striatum and in striatal target areas, i.e. globus pallidus (GP) and
      substantia nigra reticulata (SNr). Moreover, we ask whether this control is
      altered under parkinsonian conditions. Intrastriatal NMDA perfusion (10 min)
      evoked GABA release more potently in SNr (1-100 MUM) than in other regions (10
      100 MUM), suggesting preferential control over striato-nigral projection neurons.
      Intrastriatal NMDA more potently stimulated glutamate levels in the striatum (1
      100 MUM) and SNr (1-10 MUM) than in GP (10 MUM). Striatal dopamine denervation
      with 6-hydroxydopamine caused a leftward shift in the NMDA concentration-response
      curve. Intrastriatal NMDA elevated GABA levels at 0.1 MUM (all regions) and 1 MUM
      (striatum and GP only), but not at higher concentrations, indicating that,
      compared to naive animals, the GABA response in SNr was attenuated. Attenuation
      of the glutamate response was also observed in SNr (NMDA effective only at 0.1
      MUM). Conversely, the glutamate response in GP was widened (NMDA effective in the
      0.1-1 MUM range). We conclude that NMDA preferentially stimulates the activity of
      the striato-nigral direct pathway under physiological conditions. In Parkinson's
      disease, dopamine loss compromises the NMDA ability to stimulate striato-nigral
      neurons, thus shifting the NMDA control towards the striato-pallidal ones. 

PMID- 25584654
TI  - Nanoparticle delivery of chemosensitizers improve chemotherapy efficacy without
      incurring additional toxicity.
AB  - Chemosensitizers can improve the therapeutic index of chemotherapy and overcome
      treatment resistance. Successful translation of chemosensitizers depends on the
      development of strategies that can preferentially deliver chemosensitizers to
      tumors while avoiding normal tissue. We hypothesized that nanoparticle (NP)
      formulation of chemosensitizers can improve their delivery to tumors which can in
      turn improve their therapeutic index. To demonstrate the proof of principle of
      this approach, we engineered NP formulations of two chemosensitizers, the PI3
      kindase inhibitor wortmanin (Wtmn) and the PARP inhibitor olaparib. NP Wtmn and
      NP olaparib were evaluated as chemosensitizers using lung cancer cells and breast
      cancer cells respectively. We found Wtmn to be an efficient chemosensitizer in
      all tested lung-cancer cell lines reducing tumor cell growth between 20 and 60%
      compared to drug alone. NP formulation did not decrease its efficacy in vitro.
      Olaparib showed less consistent chemosensitization as a free drug or in NP
      formulation. NP Wtmn was further evaluated as a chemosensitizer using mouse
      models of lung cancer. We found that NP Wtmn is an effective chemosensitizer and
      more effective than free Wtmn showing a 32% reduction in tumor growth compared to
      free Wtmn when given with etoposide. Importantly, NP Wtmn was able to sensitize
      the multi-drug resistant H69AR cells to etoposide. Additionally, the combination
      of NP Wtmn and etoposide chemotherapy did not significantly increase toxicity.
      The present study demonstrates the proof of principle of using NP formulation of
      chemosensitizing drugs to improve the therapeutic index of chemotherapy. 

PMID- 25584656
TI  - Rapid identification and susceptibility testing of uropathogenic microbes via
      immunosorbent ATP-bioluminescence assay on a microfluidic simulator for
      antibiotic therapy.
AB  - The incorporation of pathogen identification with antimicrobial susceptibility
      testing (AST) was implemented on a concept microfluidic simulator, which is well
      suited for personalizing antibiotic treatment of urinary tract infections (UTIs).
      The microfluidic device employs a fiberglass membrane sandwiched between two
      polypropylene components, with capture antibodies immobilized on the membrane.
      The chambers in the microfluidic device share the same geometric distribution as
      the wells in a standard 384-well microplate, resulting in compatibility with
      common microplate readers. Thirteen types of common uropathogenic microbes were
      selected as the analytes in this study. The microbes can be specifically captured
      by various capture antibodies and then quantified via an ATP bioluminescence
      assay (ATP-BLA) either directly or after a variety of follow-up tests, including
      urine culture, antibiotic treatment, and personalized antibiotic therapy
      simulation. Owing to the design of the microfluidic device, as well as the
      antibody specificity and the ATP-BLA sensitivity, the simulator was proven to be
      able to identify UTI pathogen species in artificial urine samples within 20 min
      and to reliably and simultaneously verify the antiseptic effects of eight
      antibiotic drugs within 3-6 h. The measurement range of the device spreads from 1
      * 10(3) to 1 * 10(5) cells/mL in urine samples. We envision that the medical
      simulator might be broadly employed in UTI treatment and could serve as a model
      for the diagnosis and treatment of other diseases. 

PMID- 25584657
TI  - Task-switching effects for visual and auditory pro- and antisaccades: evidence
      for a task-set inertia.
AB  - The completion of an antisaccade delays the reaction time (RT) of a subsequent
      prosaccade; however, the converse switch does not influence RT. In accounting for
      this result, the task-set inertia hypothesis contends that antisaccades engender
      a persistent nonstandard task-set that delays the planning of a subsequent
      prosaccade. In contrast, the coordinate system transformation hypothesis asserts
      that the transformation required to construct a mirror-symmetrical target
      representation persistently inhibits prosaccade planning. The authors tested the
      latter hypothesis by examining switch-costs for pro- and antisaccades directed to
      visual (i.e., the stimuli used in previous work) and auditory targets. Notably,
      auditory cues are specified in a head-centered frame of reference prior to their
      conversion into the retinocentric coordinates necessary for saccade output. Thus,
      if the coordinate system transformation hypothesis is correct then auditory pro-
      and antisaccades should elicit a bidirectional switch-cost because each requires
      a coordinate transformation. RTs for visual and auditory modalities showed a
      reliable--and equivalent magnitude--prosaccade switch-cost. Moreover, performance
      (e.g., movement time) and kinematic (e.g., velocity) variables indicated the
      switch-cost was restricted to response planning. As such, results are
      incompatible with the coordinate system transformation hypothesis and therefore
      provide convergent evidence that a task-set inertia contributes to the prosaccade
      switch-cost.

PMID- 25584659
TI  - Antibiotic use in infancy and the risk of asthma in Mexican American children.
AB  - OBJECTIVE: This study examined the associations of antibiotic use in infancy with
      lifetime doctor-diagnosed asthma and current wheeze among Mexican American
      children. METHODS: In a population-based, cross-sectional investigation, parents
      of 2023 children 4-18 years of age completed a questionnaire/interview addressing
      respiratory conditions, antibiotic use, and covariates. RESULTS: In adjusted
      analyses, among children without history of ear infections in infancy, children
      who used antibiotics >=3 times and 1-2 times were more likely to report doctor
      diagnosed asthma compared with their peers who did not use antibiotics in infancy
      [adjusted odds ratio (aOR) = 5.14, 95% confidence interval (CI): 2.88-9.17, and
      aOR = 2.15, 95% CI: 1.26-3.69, respectively, p trend < 0.0001]. The respective
      aORs for current wheeze were 3.67 (95% CI: 1.95-6.89) and 1.63 (95% CI: 0.91
      2.95). Antibiotic use in infancy was not associated with asthma or current wheeze
      in children who had ear infections in infancy. In additional analyses, antibiotic
      use in infancy was associated with asthma in children without parental history of
      asthma or allergies (aOR = 2.73, 95% CI: 1.70-4.39) but not in those with
      parental history of asthma or allergies. Among Mexico-born participants born in
      rural areas, antibiotic use in infancy was associated with a seven-fold increase
      in risk of asthma (aOR = 7.21, 95% CI: 1.46-35.65), while the association was non
      significant in Mexico-born children born in urban areas in Mexico. CONCLUSIONS:
      Antibiotic use in infancy may increase the risk of asthma and wheezing, but these
      associations were limited to subgroups of children.

PMID- 25584658
TI  - Moving toward true inclusion of racial/ethnic minorities in federally funded
      studies. A key step for achieving respiratory health equality in the United
      States.
AB  - A key objective of the 1993 National Institutes of Health (NIH) Revitalization
      Act was to ensure inclusion of minorities in clinical research. We conducted a
      literature search for the period from 1993 to 2013 to examine whether
      racial/ethnic minorities are adequately represented in published research studies
      of pulmonary diseases, particularly NIH-funded studies. We found a marked
      underrepresentation of minorities in published clinical research on pulmonary
      diseases. Over the last 20 years, inclusion of members of racial or ethnic
      minority groups was reported (in MeSH terms, journal titles, and MEDLINE fields)
      in less than 5% of all NIH-funded published studies of respiratory diseases.
      Although a secondary analysis revealed that a larger proportion of NIH-funded
      studies included any minorities, this proportional increment mostly resulted from
      studies including relatively small numbers of minorities (which precludes robust
      race- or ethnic-specific analyses). Underrepresentation or exclusion of
      minorities from NIH-funded studies is likely due to multiple reasons, including
      insufficient education and training on designing and implementing population
      based studies of minorities, inadequate motivation or incentives to overcome
      challenges in the recruitment and retention of sufficient numbers of members of
      racial/ethnic minorities, underrepresentation of minorities among respiratory
      scientists in academic medical centers, and a dearth of successful partnerships
      between academic medical centers and underrepresented communities. This problem
      could be remedied by implementing short-, medium-, and long-term strategies, such
      as creating incentives to conduct minority research, ensuring fair review of
      grant applications focusing on minorities, developing the careers of minority
      scientists, and facilitating and valuing research on minorities by investigators
      of all backgrounds. 

PMID- 25584660
TI  - Los Angeles phonospirometry technique: creating a normogram that correlates with
      peak expiratory flow measurements in children.
AB  - OBJECTIVE: Measurement of peak expiratory flow (PEF) is recommended in the
      assessment of patients with asthma. However, the use of PEF involves multiple
      barriers, which have limited its use. Phonospirometry, as assessed by a novel Los
      Angeles phonospirometry technique, has shown good correlation to standard PEF
      measurements in a pilot study on symptomatic patients with asthma. We sought to
      develop a normogram for phonospirometry, and to validate the PEF normogram.
      METHODS: A convenience sample of asymptomatic children ages 3-17 years old was
      approached for participation in the Emergency Department. Sample size
      calculations determined that at least 30 children per age group (n = 450) were
      needed. Children were asked to perform PEF measurements and phonospirometry,
      measured as the length of time (in s) the child was able to chant "lalala" in a
      single breath. RESULTS: 510 children were enrolled. Spearman's rho between PEF
      and phonospirometry was 0.722. Phonospirometry correlated with both age and
      height, with a Spearman rho of 0.697 and 0.696, respectively. This was slightly
      lower than the correlation of PEF with age and height with Spearman rhos of 0.877
      and 0.902, respectively. A normogram was developed for phonospirometry based on
      age and height. CONCLUSIONS: This study determined normal value ranges for the
      Los Angeles phonospirometry technique for age and height, and also showed that
      the technique has good correlation with PEF. This technique may be used to assess
      a pediatric patient with an acute asthma exacerbation.

PMID- 25584661
TI  - Racial and ethnic differences in asthma and mental health among US adults:
      results from the National Survey on Drug Use and Health.
AB  - OBJECTIVE: Evaluate the racial and ethnic differences in asthma and mental health
      comorbidity. METHODS: A secondary analysis of 2008-2013 National Survey on Drug
      Use and Health was conducted, resulting in a total of 206 993 civilian adult
      respondents to evaluate the association between asthma and mental health (past
      year serious psychological distress [SPD] and doctor diagnosis of depression).
      Both survey weighted bivariate (chi-square) and multivariable (binary logistic)
      regression analyses, after accounting for control variables, were conducted to
      evaluate the asthma/mental health nexus. A p value of less than 0.05 was used to
      denote significance. RESULTS: Current asthma was significantly associated with
      past year SPD for non-Hispanic Whites (adjusted odds ratio [aOR] = 1.45),
      Hispanics (aOR = 1.68), and Black/African Americans (aOR = 1.47). A similar
      association was noted for current asthma and past year doctor diagnosis of
      depression (non-Hispanic White aOR = 1.74; Hispanics aOR = 1.77; Black/African
      American aOR = 1.62). Among those with lifetime asthma, higher odds of SPD were
      reported for non-Hispanic Whites (aOR = 1.42), Hispanics (aOR = 1.64), and
      Black/African Americans (aOR = 1.50). Lifetime asthma also significantly
      associated with past year doctor diagnosis of depression for non-Hispanic Whites
      (aOR = 1.42), Hispanics (aOR = 1.41), and Black/African Americans (aOR = 1.46).
      CONCLUSION: Our results demonstrate the significant burden of asthma and mental
      health comorbidity among diverse racial and ethnic groups. Improved public health
      efforts through promotion of integrated care for early screening and preventive
      measures are needed to alleviate the burden for at-risk groups.

PMID- 25584662
TI  - Anthelmintic drug discovery: into the future.
AB  - The last half-century has provided all of the (few) drugs currently used to treat
      human helminthiases. Concern regarding the long-term utility of these drugs,
      given how readily resistance evolves in the veterinary-agricultural sector, spurs
      the discovery of new chemical entities. We review the approaches and technologies
      in use to identify anthelmintics and discuss a number of drug discovery paradigms
      that may prove pivotal to the next half-century of anthelmintic development. 

PMID- 25584663
TI  - Colorimetric Method of Loop-Mediated Isothermal Amplification with the Pre
      Addition of Calcein for Detecting Flavobacterium columnare and its Assessment in
      Tilapia Farms.
AB  - Flavobacterium columnare, the causative agent of columnaris disease in fish,
      affects many economically important freshwater fish species. A colorimetric
      method of loop-mediated isothermal amplification with the pre-addition of calcein
      (LAMP-calcein) was developed and used to detect the presence of F. columnare in
      farmed tilapia (Nile Tilapia Oreochromis niloticus and red tilapia [Nile Tilapia
      * Mozambique Tilapia O. mossambicus]) and rearing water. The detection method,
      based on a change in color from orange to green, could be performed within 45 min
      at 63 degrees C. The method was highly specific, as it had no cross-detections
      with 14 other bacterial species, including other fish pathogens and two
      Flavobacterium species. The method has a minimum detection limit of 2.2 * 10(2)
      F. columnare CFU; thus, it is about 10 times more sensitive than conventional
      PCR. With this method, F. columnare was detected in gonad, gill, and blood
      samples from apparently healthy tilapia broodstock as well as in samples of
      fertilized eggs, newly hatched fry, and rearing water. The bacteria isolated from
      the blood were further characterized biochemically and found to be phenotypically
      identical to F. columnare. The amplified products from the LAMP-calcein method
      had 97% homology with the DNA sequence of F. columnare.

PMID- 25584665
TI  - Occupational Stress Among Australian Podiatric Physicians in General and
      Geriatric Practice.
AB  - BACKGROUND: High levels of occupational stress have been reported in podiatrists
      practising in Australia. One possible stressor is the predominance of the
      treatment of aged patients with chronic disease in Podiatry practice.
      METHODS:Forty (40) Podiatrists attending a regional podiatry conference were
      invited to participate in the research using a convenience sampling method.
      Podiatrists were asked to complete a survey examining occupational stress in
      general and specifically in relation to practice with older adults (defined as
      those over the age of sixty five). RESULTS:The survey of sources of occupational
      stress among podiatrists has identified that patient demands and expectations are
      the most significant stressor both in general and in geriatric practice for the
      Podiatrist. The perceived limited clinical gains and chronic nature of their
      conditions in older patients was also ranked highly as a stressor.
      CONCLUSIONS:Working with the elderly is a significant part of podiatry practice
      and as such needs to be seen with more positive attitude by many practitioners.
      The development of geriatric practice as a speciality within the profession may
      help to raise the value of working with the elderly. This has implications for
      preparing podiatrists for practice with the geriatric population along with the
      need for strategies to avoid or minimise these work stressors.

PMID- 25584666
TI  - Analyses of the cell mechanical damage during microinjection.
AB  - The microinjection is an essential technique to introduce foreign materials into
      biological cells. The soft cell is inevitably ruptured by the microinjector
      during microinjection. We discuss the way to reduce the mechanical damage by
      analyzing the control parameters during microinjection. The computational model
      is developed with the dissipative particle dynamics to simulate the soft
      mechanical properties of biological cells. The cell model contains the membrane
      networks, the internal cytoskeleton, crosslink proteins, motors and their
      functions. The weak power law rheology verifies our computational model. The
      number of ruptured bonds is used to describe the extent of the mechanical damage
      that the cell experiences during microinjection. Some experiments are conducted
      on the Zebrafish embryos. Both the simulation works and experimental results show
      that the size, shape of the microinjector tip, and the injection velocity have a
      significant influence on the cell damage. A small, sharp microinjector with a
      high velocity can reduce the mechanical damage. 

PMID- 25584664
TI  - Our Choice/Nuestra Opcion: the Imperial County, California, Childhood Obesity
      Research Demonstration study (CA-CORD).
AB  - BACKGROUND: Despite recent declines among young children, obesity remains a
      public health burden in the United States, including among Latino/Hispanic
      children. The determining factors are many and are too complex to fully address
      with interventions that focus on single factors, such as parenting behaviors or
      school policies. In this article, we describe a multisector, multilevel
      intervention to prevent and control childhood obesity in predominantly Mexican
      origin communities in Southern California, one of three sites of the CDC-funded
      Childhood Obesity Research Demonstration (CA-CORD) study. METHODS: CA-CORD is a
      partnership between a university-affiliated research institute, a federally
      qualified health center, and a county public health department. We used formative
      research, advisory committee members' recommendations, and previous research to
      inform the development of the CA-CORD project. Our theory-informed multisector,
      multilevel intervention targets improvements in four health behaviors: fruit,
      vegetable, and water consumption; physical activity; and quality sleep.
      Intervention partners include 1200 families, a federally qualified health center
      (including three clinics), 26 early care and education centers, two elementary
      school districts (and 20 elementary schools), three community recreation centers,
      and three restaurants. Intervention components in these sectors target changes in
      behaviors, policies, systems, and the social and physical environment. Evaluation
      activities include assessment of the primary outcome, BMI z-score, at baseline,
      12-, and 18-months post-baseline, and sector evaluations at baseline, 12, and 24
      months. CONCLUSIONS: Identifying feasible and effective strategies to prevent and
      control childhood obesity has the potential to effect real changes in children's
      current and future health status.

PMID- 25584677
TI  - Corrigendum. Patterns of functioning in older adults with mild cognitive
      impairment: a two-year study focusing on everyday technology use.

PMID- 25584678
TI  - An oncogenic enhancer enemy (N-Me) in T-ALL.

PMID- 25584679
TI  - Chemical functionalization of graphene to augment stem cell osteogenesis and
      inhibit biofilm formation on polymer composites for orthopedic applications.
AB  - Toward designing the next generation of resorbable biomaterials for orthopedic
      applications, we studied poly(epsilon-caprolactone) (PCL) composites containing
      graphene. The role, if any, of the functionalization of graphene on mechanical
      properties, stem cell response, and biofilm formation was systematically
      evaluated. PCL composites of graphene oxide (GO), reduced GO (RGO), and amine
      functionalized GO (AGO) were prepared at different filler contents (1%, 3%, and
      5%). Although the addition of the nanoparticles to PCL markedly increased the
      storage modulus, this increase was largest for GO followed by AGO and RGO. In
      vitro cell studies revealed that the AGO and GO particles significantly increased
      human mesenchymal stem cell proliferation. AGO was most effective in augmenting
      stem cell osteogenesis leading to mineralization. Bacterial studies revealed that
      interaction with functionalized GO induced bacterial cell death because of
      membrane damage, which was further accentuated by amine groups in AGO. As a
      result, AGO composites were best at inhibiting biofilm formation. The synergistic
      effect of oxygen containing functional groups and amine groups on AGO imparts the
      optimal combination of improved modulus, favorable stem cell response, and
      biofilm inhibition in AGO-reinforced composites desired for orthopedic
      applications. This work elucidates the importance of chemical functionalization
      of graphene in polymer composites for biomedical applications. 

PMID- 25584680
TI  - Large-scale growth of hierarchical transition-metal vanadate nanosheets on metal
      meshes as monolith catalysts for De-NO(x) reaction.
AB  - A facile method is developed for the large-scale growth of hierarchical
      transition-metal (Cu, Fe, and Ni) vanadate nanosheets on corresponding metal mesh
      as supports. The hierarchical transition-metal vanadate nanosheets were in situ
      grown on the metal meshes through an orientational etching process and
      simultaneous nucleation and growth process. Interestingly, the morphologies of
      the vanadate nanosheets are governed by the balance between dissolution rate and
      nucleation rate. Thus, the sizes and the thicknesses of the nanosheets could be
      facilely controlled by the reaction duration, the acidity of the solution and the
      concentration of vanadate precursor. Furthermore, the hierarchical transition
      metal vanadate nanosheets supported on metal meshes are used as monolith
      catalysts for the selective catalytic reduction (SCR) of NO with NH3. The iron
      mesh based monolith catalyst shows excellent de-NOx performance with high
      efficiency and stability in the presence of SO2 and H2O, which provide a
      promising monolith de-NOx catalyst for stationary source at medium temperatures. 

PMID- 25584681
TI  - Recent modifications of chitosan for adsorption applications: a critical and
      systematic review.
AB  - Chitosan is considered to be one of the most promising and applicable materials
      in adsorption applications. The existence of amino and hydroxyl groups in its
      molecules contributes to many possible adsorption interactions between chitosan
      and pollutants (dyes, metals, ions, phenols, pharmaceuticals/drugs, pesticides,
      herbicides, etc.). These functional groups can help in establishing positions for
      modification. Based on the learning from previously published works in
      literature, researchers have achieved a modification of chitosan with a number of
      different functional groups. This work summarizes the published works of the last
      three years (2012-2014) regarding the modification reactions of chitosans
      (grafting, cross-linking, etc.) and their application to adsorption of different
      environmental pollutants (in liquid-phase). 

PMID- 25584684
TI  - Poly(3-hexylthiophene) nanotube array surfaces with tunable wetting and contact
      thermal energy transport.
AB  - Solution casting using a sacrificial template is a simple technique to fabricate
      vertical arrays of polymer nanotubes. However, because of their close proximity
      and high aspect ratios, large capillary forces cause nanotubes to cluster as the
      array dries; researchers often use special drying techniques to avoid this
      clustering. Here, we exploit the clustering of regioregular poly(3
      hexylthiophene) (rr-P3HT) nanotubes in a unique template etching process to
      create surfaces that exhibit tunable wetting and contact thermal energy
      transport. Vertical arrays of rr-P3HT nanotubes are cast from solution in
      nanoscale alumina templates, and a solution etching process is used to partially
      release the nanotubes from the template. The clustering of rr-P3HT nanotube tips
      upon template etching produces hierarchical surface structuring with a distinct
      pattern of interconnected ridges, and the spacing between the ridges increases
      with increased template etch times. These changes in morphology cause the water
      contact angle to increase from 141 degrees  to 168 degrees  as the etch time is
      increased from 4 to 12 min. When assembled into an interface, the morphological
      changes cause the thermal contact resistance of the vertical rr-P3HT nanotube
      arrays to increase linearly at a rate of approximately 6 mm(2).K/W per 2 min etch
      interval (after 6 min of etching is surpassed). The effective thermal
      conductivity of the rr-P3HT nanotube arrays is 1 +/- 0.2 W/mK independent of the
      etch time, which is approximately 5 times higher than the bulk rr-P3HT film
      value. 

PMID- 25584682
TI  - Preparation of photocrosslinked fish elastin polypeptide/microfibrillated
      cellulose composite gels with elastic properties for biomaterial applications.
AB  - Photocrosslinked hydrogels reinforced by microfibrillated cellulose (MFC) were
      prepared from a methacrylate-functionalized fish elastin polypeptide and MFC
      dispersed in dimethylsulfoxide (DMSO). First, a water-soluble elastin peptide
      with a molecular weight of ca. 500 g/mol from the fish bulbus arteriosus was
      polymerized by N,N'-dicyclohexylcarbodiimide (DCC), a condensation reagent, and
      then modified with 2-isocyanatoethyl methacrylate (MOI) to yield a
      photocrosslinkable fish elastin polypeptide. The product was dissolved in DMSO
      and irradiated with UV light in the presence of a radical photoinitiator. We
      obtained hydrogels successfully by substitution of DMSO with water. The composite
      gel with MFC was prepared by UV irradiation of the photocrosslinkable elastin
      polypeptide mixed with dispersed MFC in DMSO, followed by substitution of DMSO
      with water. The tensile test of the composite gels revealed that the addition of
      MFC improved the tensile properties, and the shape of the stress-strain curve of
      the composite gel became more similar to the typical shape of an elastic material
      with an increase of MFC content. The rheology measurement showed that the elastic
      modulus of the composite gel increased with an increase of MFC content. The cell
      proliferation test on the composite gel showed no toxicity. 

PMID- 25584686
TI  - Fabrication of shape controllable Janus alginate/pNIPAAm microgels via
      microfluidics technique and off-chip ionic cross-linking.
AB  - A novel method to fabricate shape controllable alginate/pNIPAAm complex microgels
      is reported. Monodisperse alginate/pNIPAAm droplets are created via microfluidics
      and cross-linked in different concentrations of hot glycerol/barium acetate water
      solutions. By changing the initial droplet size and glycerol concentration of the
      collecting solution, the resultant microgel shape and surface details can be
      systematically tuned. High-speed imaging is used to visualize and explain the
      microgel formation process. 

PMID- 25584683
TI  - Preparative separation of sulfur-containing diketopiperazines from marine fungus
      Cladosporium sp. using high-speed counter-current chromatography in stepwise
      elution mode.
AB  - High-speed counter-current chromatography (HSCCC) was successively applied to the
      separation of three sulfur-containing diketopiperazines (DKPs) (including two new
      compounds cladosporin A (1) and cladosporin B (3), and a known compound
      haematocin (2)) from a marine fungus Cladosporium sp. The two-phase solvent
      system composed of n-hexane-ethyl acetate-methanol-water at (1:1:1:1, v/v) and
      (2:1:2:1, v/v), in stepwise elution mode, was used for HSCCC. The preparative
      HSCCC separation was performed on 300 mg of crude sample yielding 26.7 mg of
      compound 3 at a purity of over 95%, 53.6 mg of a mixture of compounds 1 and 2,
      which was further separated by preparative-HPLC yielding 14.3 mg of compound 1
      and 25.4 mg of compound 2 each at a purity of over 95%. Their structures were
      established by spectroscopic methods. The sulfur-containing DKPs suppressed the
      proliferation of hepatocellular carcinoma cell line HepG2. The present work
      represents the first application of HSCCC in the efficient preparation of marine
      fungal natural products. 

PMID- 25584685
TI  - UV disinfection induces a VBNC state in Escherichia coli and Pseudomonas
      aeruginosa.
AB  - The occurrence of a viable but nonculturable (VBNC) state in bacteria may
      dramatically underestimate the health risks associated with drinking water.
      Therefore, the potential for UV treatment to induce a VBNC state in Escherichia
      coli and Pseudomonas aeruginosa was investigated. UV disinfection effectively
      reduced the culturability of E. coli and P. aeruginosa, with the destruction of
      nucleic acids demonstrated using gadA long gene fragment qPCR amplification.
      Following UV radiation, copy numbers for the high transcriptional levels of the
      16S rRNA gene varied insignificantly in both strains, confirming results from
      plate counting assays indicating that VBNC states were induced in both strains.
      Furthermore, the virulence genes gadA and oprL remained highly expressed,
      suggesting that the VBNC bacteria still displayed pathogenicity. Propidium
      monoazide qPCR indicated that cell membranes remained intact even at a UV dose of
      300 mJ/cm(2). The RT-qPCR results after UV and chlorine treatments in E. coli
      were significantly different (8.41 and 5.59 log units, respectively), further
      confirming the induction of VBNC bacteria induced by UV radiation. Finally,
      resuscitation was achieved, with E. coli showing greater resuscitation ability
      than P. aeruginosa. These results systematically revealed the potential health
      risks of UV disinfection and strongly suggest a combined disinfection strategy. 

PMID- 25584687
TI  - Design, synthesis, and biological evaluation of combretabenzodiazepines: a novel
      class of anti-tubulin agents.
AB  - In the present manuscript, starting from the 1,4-benzodiazepin-2-one nucleus, a
      privileged structure in medicinal chemistry, we have synthesized a novel class of
      cis-locked combretastatins named combreatabenzodiazepines. They show similar
      cytotoxic and antitubulin activity compared to combretastatin A-4 in
      neuroblastoma cells, showing a better pharmacokinetic profile. This class of
      compounds has therefore the potential for further development as antitubulin
      agents. 

PMID- 25584689
TI  - Terminal U=E (E = N, P, As, Sb, and Bi) bonds in uranium complexes: a theoretical
      perspective.
AB  - The compound L-U-N [L = [N(CH2CH2NSiPr(i)3)3](3-), Pr(i) = CH(CH3)2] containing a
      terminal U-N triple bond has been synthesized and isolated successfully in
      experiments. To investigate the trend in the bonding nature of its pnictogen
      analogues, we have studied the L-U-E (E = N, P, As, Sb, and Bi) complexes using
      the scalar relativistic density functional theory. The terminal U-E multiple bond
      length increases in the order of U-N ? U-P < U-As < U-Sb < U-Bi, which can be
      supported by the hard and soft acids and bases (HSAB) theory. The U-E bond
      length, molecular orbital (MO), and natural bond orbital (NBO) reveal that the
      terminal U-E bonds should be genuine triple bonds containing one sigma- and two
      pi-bonding orbitals. Quantum theory of atoms in molecules (QTAIM) topological
      analysis and the electron localization function (ELF) suggest that the terminal U
      E bond possesses covalent character and the covalency of U-E bonds decrease
      sharply when the terminal atom becomes heavier. This work presents a comparison
      about the bonding characteristic between the terminal U=N bond and its heavier
      pnictogen (P, As, Sb, and Bi) analogues. It is expected that this work would shed
      light on the evaluation of the amount of 5f orbital participation in multiple
      bonds and further facilitate our deeper understanding of f-block elements. 

PMID- 25584690
TI  - Molecular mechanism behind the synergistic activity of diphenylmethyl
      selenocyanate and Cisplatin against murine tumor model.
AB  - Various preclinical, clinical and epidemiological studies have already well
      established the cancer chemopreventive and chemoprotective potential of selenium
      compounds. In addition to its protective efficacy, recent studies have also
      proved the abilities of selenium compounds to induce cell death specifically in
      malignant cells. Therefore, our intention is to improve the therapeutic efficacy
      of an alkylating agent, cisplatin, by the adjuvant use of an organoselenium
      compound, diphenylmethyl selenocyanate (DMSE). It was observed that combined
      treatment decreased the tumor burden significantly through reactive oxygen
      species generation and modulation of antioxidant and detoxifying enzyme system in
      tumor cells. These activities ultimately led to significant DNA damage and
      apoptosis in tumor cells. Study of the molecular pathway disclosed that the
      adjuvant treatment caused induction of p53, Bax and suppressed Bcl-2 followed by
      the activation of caspase cascade. Furthermore, a concomitant decrease in
      cisplatin-induced nephrotoxicity and hematopoietic toxicity by DMSE might also
      have enhanced the efficacy of cisplatin and provided survival advantage to the
      host. Results suggested that the combination treatment with DMSE and cisplatin
      may offer potential therapeutic benefit, and utilization of cisplatin in cancer
      chemotherapy exempt of its limitations.

PMID- 25584688
TI  - Improved PeT molecules for optically sensing voltage in neurons.
AB  - VoltageFluor (VF) dyes have the potential to measure voltage optically in
      excitable membranes with a combination of high spatial and temporal resolution
      essential to better characterize the voltage dynamics of large groups of
      excitable cells. VF dyes sense voltage with high speed and sensitivity using
      photoinduced electron transfer (PeT) through a conjugated molecular wire. We show
      that tuning the driving force for PeT (DeltaGPeT + w) through systematic chemical
      substitution modulates voltage sensitivity, estimate (DeltaGPeT + w) values from
      experimentally measured redox potentials, and validate the voltage sensitivities
      in patch-clamped HEK cells for 10 new VF dyes. VF2.1(OMe).H, with a 48% DeltaF/F
      per 100 mV, shows approximately 2-fold improvement over previous dyes in HEK
      cells, dissociated rat cortical neurons, and medicinal leech ganglia.
      Additionally, VF2.1(OMe).H faithfully reports pharmacological effects and circuit
      activity in mouse olfactory bulb slices, thus opening a wide range of previously
      inaccessible applications for voltage-sensitive dyes. 

PMID- 25584691
TI  - Combined anticancer therapies: an overview of the latest applications.
AB  - Tumor resistance and low drug efficacy prompt to investigate new therapeutic
      strategies that have high efficacy and low toxicity, especially for cancers with
      poor prognosis. This goal has been recently achieved using particular
      pharmaceutical combination or nanotechnologies to specifically deliver drugs at
      the tumor site. Novel combined treatments employ either naturally active
      ingredients or drugs already intended for other uses, with the aim to increase
      cell sensitivity to therapy and reduce drug toxicity. Combined treatments usually
      improve the overall therapeutic efficacy of the single drug. Drug-drug
      interactions allow synergistic effects. Several evidences indicate that synergy
      can be affected by drug-drug ratio and drug administration order. Therapeutic
      efficacy can be enhanced through drug entrapment in nanocarriers that allow a
      site-specific targeting, resulting in a build-up of the drug in the tumor with a
      significant toxicity reduction. Several studies investigated combined entrapment
      of two or more drugs each one characterized by different mechanisms of action.
      These nanosystems improve synergistic efficacy and could be a device to resolve
      toxicity and multi-drug resistance. Nano-encapsulation of anticancer agents by
      targeting specific tumor tissues significantly optimizes drug bioavailability,
      biocompatibility and therapeutic efficacy. The efficacy of these formulations
      results from receptor-mediated endocytosis and prolonged circulation time. Drug
      encapsulation also allows using limited final concentration while avoiding its
      activity within the blood circulation. In this review we report recent findings
      about novel combined treatment focusing on synergistic effects and mechanisms of
      action. We will also overview the latest drug delivery system and their
      therapeutic benefits in cancer treatment.

PMID- 25584692
TI  - Exploring Cancer Therapeutics with Natural Products from African Medicinal
      Plants, Part I: Xanthones, Quinones, Steroids, Coumarins, Phenolics and other
      Classes of Compounds.
AB  - Cancer is known to be the second most common disease-related cause of death among
      humans. In drug discovery programs anti-cancer chemotherapy remains quite
      challenging due to issues related to resistance. Plants used in traditional
      medicine are known to contribute significantly within a large proportion of the
      African population. A survey of the literature has led to the identification of
      ~400 compounds from African medicinal plants, which have shown anti-cancer, anti
      proliferation, anti-tumor and/or cytotoxic activities, tested by in vitro and in
      vivo assays (from mildly active to very active), mainly alkaloids, terpenoids,
      flavonoids, coumarins, phenolics, polyacetylates, xanthones, quinones, steroids
      and lignans. The first part of this review series focuses on xanthones, quinones,
      steroids, coumarins, phenolics and other compound classes, while part II is
      focused on alkaloids, terpenoids, flavonoids. 

PMID- 25584693
TI  - Current perspective of natural alkaloid carbazole and its derivatives as
      antitumor agents.
AB  - Throughout our evolution, the importance of natural products for medicine and
      health has been increasing and it continues to be a key source of novel
      anticancer drugs, leads and new chemical entities. Among natural products,
      tricyclic heteroaromatic alkaloids such as carbazoles are an important class of
      natural and semi-synthetic organic compounds. In the last few decades medicinal
      role of natural and semi-synthetic carbazoles has expanded significantly,
      especially as a vital heterocyclic class of antitumor agents. Some of the
      carbazoles that displayed potential anticancer activity have undergone clinical
      trials. However, complications arising due to multidrug resistance in clinical
      trials led to very few of the selected carbazoles being approved for cancer
      therapy. Planar, polycyclic and aromatic carbazoles exhibit anticancer activity
      via DNA intercalation. Further many carbazoles can be cytotoxic by inhibiting DNA
      dependent enzymes such as telomerase and topoisomerase I/II. 

PMID- 25584694
TI  - Acridone-based antitumor agents: a mini-review.
AB  - In the past decades, tricyclic acridone ring system has become one of the major
      research interests of the medicinal chemists due to the biological significance
      of this moiety in drug design and drug discovery. Acridone scaffold has
      substantial bio-potential since it possess crucial activities such as
      antibacterial, antimalarial, antiviral and anti-neoplastic. The diverse
      biological activity of acridone and its prospective in reversal of multi-drug
      resistance has attracted attention of medicinal chemists to explore this scaffold
      especially to treat multi-drug resistance in cancer. Considering this potential
      in this review we have summarized the synthesis and the antitumor activities of
      different acridone derived compounds reported from 2000 to 2014. 

PMID- 25584695
TI  - Recent Advance in Drug Development of Squamous Cell Carcinoma.
AB  - Squamous cell carcinoma (SCC) has a high worldwide incidence that is commonly
      seen as head and neck cancers, esophageal cancers, and non-small cell lung
      cancers. There is a poor prognosis for SCC due to potential recurrence and its
      metastatic tendency so the 5-year survival rate is very low. Target therapy is a
      novel and promising treatment strategy exhibiting great anti-tumor effects and
      survival benefits in SCC. This review summarizes current treatment strategies
      from clinical and experimental studies, including the agents targeting epidermal
      growth factor receptors, RNA polymerase, toll-like receptors, p38alpha MAPK,
      CXCR, and the related combination therapy regimens. However, there are still many
      challenges we have to face. It is a burning need to improve the development and
      availability of drug formulations. 

PMID- 25584696
TI  - Development of Fourth Generation ABC Inhibitors from Natural Products: A Novel
      Approach to Overcome Cancer Multidrug Resistance.
AB  - Multidrug resistance (MDR) in cancer caused due to overexpression of ABC drug
      transporters is a major problem in modern chemotherapy. Molecular investigations
      on MDR have revealed that the resistance is due to various transport proteins of
      the ABC superfamily which include Phosphoglycoprotein (P-gp/MDR1/ ABCB1),
      multidrug resistance-associated protein-1 (MRP1), and the breast cancer
      resistance protein (BCRP). They have been characterized functionally and are
      considered as major players in the development of MDR in cancer cells. These ATP
      dependent transporter proteins cause MDR either by decreased uptake of the drug
      or increased efflux of the drug from the target organelles. Several MDR-reversing
      agents are being developed and are in various stages of clinical trials. The
      first three generations of ABC modulators such as quinine, verapamil,
      cyclosporine-A, tariquitor, PSC 833, LY335979, and GF120918 required to be
      administered in high doses to reverse MDR and were associated with adverse
      effects. Additionally, these modulators non-selectively inhibit ABC and adversely
      accumulate chemotherapeutic drugs in brain and kidney. Currently, research has
      stepped up towards reversing MDR by using natural products which exhibitted
      potential as chemosensitizers. Globally, there is a rich biodiversity of natural
      products which can be sourced for developing drugs. These products may provide
      more lead compounds with superior activity, foremost to the development of more
      effective therapies for MDR cancer cells. Here, we briefly review the status of
      natural products for reversing MDR modulators, and discuss the long term goal of
      MDR strategies in current clinical settings. 

PMID- 25584697
TI  - A synthetic approach to N-aryl carbamates via copper-catalyzed Chan-Lam coupling
      at room temperature.
AB  - A mild and efficient synthesis of N-arylcarbamates was achieved by reacting
      azidoformates with boronic acids in the presence of 10 mol % of copper chloride
      catalyst. The reaction proceeds readily in an open flask at room temperature
      without additional base, ligand, or additive. Rapid access to urea analogues via
      a two-step one-pot procedure is enabled by reacting N-arylcarbamates with
      aluminum-amine complexes. In addition, among several boronic acid derivatives
      prepared, dimethylphenyl boronate was found to react rapidly in its reaction with
      benzyl azidoformate, invoking in situ generation of this species in the catalytic
      cycle. 

PMID- 25584698
TI  - Asymmetric dearomatization of 1-aminonaphthalene derivatives by gold-catalyzed
      intramolecular double C-C bond formation.
AB  - It has been established that a cationic gold(I)/axially chiral biaryl
      bisphosphine complex catalyzes asymmetric dearomatization of 1-aminonaphthalene
      derivatives by the intramolecular double C-C bond formation. Two different
      dearomatization products were obtained depending on the substituents on the
      benzyl groups at the alkyne termini. 

PMID- 25584699
TI  - Au-embedded ZnO/NiO hybrid with excellent electrochemical performance as advanced
      electrode materials for supercapacitor.
AB  - Here we design a nanostructure by embedding Au nanoparticles into ZnO/NiO core
      shell composites as supercapacitors electrodes materials. This optimized hybrid
      electrodes exhibited an excellent electrochemical performance including a long
      term cycling stability and a maximum specific areal capacitance of 4.1 F/cm(2) at
      a current density of 5 mA/cm(2), which is much higher than that of ZnO/NiO
      hierarchical materials (0.5 F/cm(2)). Such an enhanced property is attributed to
      the increased electro-electrolyte interfaces, short electron diffusion pathways
      and good electrical conductivity. Apart from this, electrons can be temporarily
      trapped and accumulated at the Fermi level (EF') because of the localized
      schottky barrier at Au/NiO interface in charge process until fill the gap between
      ZnO and NiO, so that additional electrons can be released during discharge. These
      results demonstrate that suitable interface engineering may open up new
      opportunities in the development of high-performance supercapacitors. 

PMID- 25584700
TI  - Formation of a CH-pi contact in the core of native barstar during folding.
AB  - An important part of the protein folding process is the consolidation of the
      protein core through the formation of specific, directional contacts after the
      initial hydrophobic collapse. Here, we simultaneously monitor formation of core
      contacts and assembly of secondary structure through salt-induced folding by
      using resonance Raman spectroscopy. Unfolded barstar at pH 12 was refolded by
      gradual addition of sodium sulfate salt. Altered spectral characteristics of the
      Trp53 residue suggest that the core of the protein attains a CH-pi interaction at
      a low concentration of the salt, with an increase in the packing density. Further
      increase in salt concentration produces a reduction in the solvent accessibility
      of the core. These data provide evidence that the core of the protein becomes
      rigid upon the addition of 0.6 M sodium sulfate. This is the first time that the
      formation of a CH-pi interaction has been directly monitored during the folding
      of a protein. 

PMID- 25584701
TI  - High-resolution patterns of quantum dots formed by electrohydrodynamic jet
      printing for light-emitting diodes.
AB  - Here we demonstrate materials and operating conditions that allow for high
      resolution printing of layers of quantum dots (QDs) with precise control over
      thickness and submicron lateral resolution and capabilities for use as active
      layers of QD light-emitting diodes (LEDs). The shapes and thicknesses of the QD
      patterns exhibit systematic dependence on the dimensions of the printing nozzle
      and the ink composition in ways that allow nearly arbitrary, systematic control
      when exploited in a fully automated printing tool. Homogeneous arrays of patterns
      of QDs serve as the basis for corresponding arrays of QD LEDs that exhibit
      excellent performance. Sequential printing of different types of QDs in a
      multilayer stack or in an interdigitated geometry provides strategies for
      continuous tuning of the effective, overall emission wavelengths of the resulting
      QD LEDs. This strategy is useful to efficient, additive use of QDs for wide
      ranging types of electronic and optoelectronic devices. 

PMID- 25584702
TI  - Operating Characteristics of Statistical Methods for Detecting Gene-by-Measured
      Environment Interaction in the Presence of Gene-Environment Correlation under
      Violations of Distributional Assumptions.
AB  - Accurately identifying interactions between genetic vulnerabilities and
      environmental factors is of critical importance for genetic research on health
      and behavior. In the previous work of Van Hulle et al. (Behavior Genetics, Vol.
      43, 2013, pp. 71-84), we explored the operating characteristics for a set of
      biometric (e.g., twin) models of Rathouz et al. (Behavior Genetics, Vol. 38,
      2008, pp. 301-315), for testing gene-by-measured environment interaction (GxM) in
      the presence of gene-by-measured environment correlation (rGM) where data
      followed the assumed distributional structure. Here we explore the effects that
      violating distributional assumptions have on the operating characteristics of
      these same models even when structural model assumptions are correct. We
      simulated N = 2,000 replicates of n = 1,000 twin pairs under a number of
      conditions. Non-normality was imposed on either the putative moderator or on the
      ultimate outcome by ordinalizing or censoring the data. We examined the empirical
      Type I error rates and compared Bayesian information criterion (BIC) values. In
      general, non-normality in the putative moderator had little impact on the Type I
      error rates or BIC comparisons. In contrast, non-normality in the outcome was
      often mistaken for or masked GxM, especially when the outcome data were censored.

PMID- 25584703
TI  - Characterization and Comparison of Wine Lees by Liquid Chromatography-Mass
      Spectrometry in High-Resolution Mode.
AB  - Wine lees from 11 different wineries pertaining to two denominations of origin in
      Spain (La Rioja and Ribera del Duero) have been characterized in this research by
      LC-MS/MS in high-resolution mode. For this purpose, the wine lees were separated
      into the liquid phase (imbibed wine from lees) and the solid residue, which was
      dried and subjected to solid-liquid extraction assisted by microwaves (dried
      lees). Both fractions were separately analyzed and the fractions from the 11
      wineries compared to find similarity in their patterns. The statistical analysis
      enabled both differences and common aspects in the composition of imbibed wine
      from lees and dried lees from all wineries to be found. MS/MS tentative
      identification of representative compounds in each fraction revealed the varied
      composition of wine lees with special emphasis on flavonoids such as quercetin,
      myricetin, and malvidin 3-galactoside, identified in extracts of dried lees, or
      other compounds such as kaempferol 3-(2',3'-diacetylrhamnoside)-7"-rhamnoside,
      aminocaproic acid, and citric acid, exclusively identified in imbibed wine from
      lees. The adsorbent capacity of the solid residue justified the high
      concentration of phenolic compounds in the extracts from solid lees. The
      differences found in the composition of the two phases support the separated
      exploitation of them.

PMID- 25584705
TI  - Enhanced reactivity of dendrons in the Passerini three-component reaction.
AB  - Polymer chemistry has embraced multicomponent reactions for synthesizing
      multifunctional materials, including structurally perfect multimodal dendrimers.
      An unexpected substituent effect dramatically shortens the time required for the
      convergent synthesis of dendrimers via the Passerini three-component reaction. 

PMID- 25584704
TI  - The C-terminal RNA binding motif of HuR is a multi-functional domain leading to
      HuR oligomerization and binding to U-rich RNA targets.
AB  - Human antigen R (HuR) is a 32 kDa protein with 3 RNA Recognition Motifs (RRMs),
      which bind to Adenylate and uridylate Rich Elements (AREs) of mRNAs. Whereas the
      N-terminal and central domains (RRM1 and RRM2) are essential for AREs
      recognition, little is known on the C-terminal RRM3 beyond its implication in HuR
      oligomerization and apoptotic signaling. We have developed a detergent-based
      strategy to produce soluble RRM3 for structural studies. We have found that it
      adopts the typical RRM fold, does not interact with the RRM1 and RRM2 modules,
      and forms dimers in solution. Our NMR measurements, combined with Molecular
      Dynamics simulations and Analytical Ultracentrifugation experiments, show that
      the protein dimerizes through a helical region that contains the conserved W261
      residue. We found that HuR RRM3 binds to 5'-mer U-rich RNA stretches through the
      solvent exposed side of its beta-sheet, located opposite to the dimerization
      site. Upon mimicking phosphorylation by the S318D replacement, RRM3 mutant shows
      less ability to recognize RNA due to an electrostatic repulsion effect with the
      phosphate groups. Our study brings new insights of HuR RRM3 as a domain involved
      in protein oligomerization and RNA interaction, both functions regulated by 2
      surfaces on opposite sides of the RRM domain. 

PMID- 25584707
TI  - Local Staging of Soft-Tissue Sarcoma: Emphasis on Assessment of Neurovascular
      Encasement-Value of MR Imaging in 174 Confirmed Cases.
AB  - PURPOSE: To evaluate utility of magnetic resonance (MR) imaging in local staging
      of soft-tissue sarcoma, with an emphasis on assessment of neurovascular
      encasement. MATERIALS AND METHODS: Institutional review board approval was
      obtained; informed consent requirement was waived. Preoperative MR images in 174
      patients with soft-tissue sarcoma were analyzed by two readers. Tumor staging
      according to the American Joint Committee on Cancer/Union International Contre le
      Cancer and Enneking staging systems and analysis of osseous and articular
      invasion were performed. To assess neurovascular encasement, contact between
      tumor and arteries, between tumor and veins, and between tumor and nerves was
      classified (no contact, contact <=90 degrees , 91 degrees -180 degrees , 181
      degrees -270 degrees , >271 degrees ). Interobserver agreement was determined;
      imaging findings were correlated with intraoperative findings and/or
      histopathologic findings (Pearson correlation coefficient [r] and Cohen kappa
      coefficient). RESULTS: Intraoperative evaluation and/or histopathologic
      evaluation confirmed osseous, articular, and neurovascular invasion in 8.6%,
      2.9%, and 25.3% of patients. Interobserver agreement was excellent for tumor
      staging (American Joint Committee on Cancer/Union International Contre le Cancer
      staging, kappa = 0.811; Enneking staging, kappa = 0.943) and osseous invasion
      (kappa = 1.000). It was substantial for articular invasion (kappa = 0.794).
      Sensitivity and specificity for osseous invasion were 100% and 98.7%,
      respectively (both readers). For articular invasion, sensitivity was 80% (both
      readers); specificities were 100% and 98.8% for readers 1 and 2, respectively.
      Interobserver agreement in quantifying contact between tumor and vessels and
      between tumor and nerves was excellent for arteries, veins, and nerves (kappa =
      0.845, 0.892, 0.893, respectively). Receiver operating characteristic analysis
      revealed optimal threshold of greater than 180 degrees  for prediction of
      arterial and venous encasement (both readers). For neural encasement, optimal
      threshold was greater than 180 degrees  (reader 1) and greater than 270 degrees 
      (reader 2). Sensitivities in diagnosing encasement for arteries, veins, and
      nerves were 84.6%, 84.6%, and 77.8% (reader 1) and 84.6%, 84.6%, and 72.2%
      (reader 2). Specificities for encasement of arteries, veins, and nerves,
      respectively, were 97.5%, 97.5%, and 93.2% (reader 1) and 93.8%, 94.7%, 97.3%
      (reader 2). CONCLUSION: MR imaging allows reliable and accurate local staging of
      soft-tissue sarcoma. Encasement of arteries, veins, and nerves should be
      diagnosed, if the contact between tumor and vascular or neural circumference
      exceeds 180 degrees .

PMID- 25584706
TI  - Pre-Radiation Therapy Fluorine 18 Fluorodeoxyglucose PET Helps Identify Patients
      with Esophageal Cancer at High Risk for Radiation Pneumonitis.
AB  - PURPOSE: To examine the association between pre-radiation therapy (RT) fluorine
      18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis
      (RP). MATERIALS AND METHODS: In accordance with the retrospective study protocol
      approved by the institutional review board, 228 esophageal cancer patients who
      underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were
      evaluated by using the Common Terminology Criteria for Adverse Events, version
      4.0, from the consensus of five clinicians. By using the cumulative distribution
      of standardized uptake values (SUVs) within the lungs, those values greater than
      80%-95% of the total lung voxels were determined for each patient. The effect of
      pre-chemotherapy and RT FDG uptake, dose, and patient or treatment
      characteristics on RP toxicity was studied by using logistic regression. RESULTS:
      The study subjects were treated with three-dimensional conformal RT (n = 36),
      intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression
      analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related
      to expression of RP symptoms. Study subjects with elevated 95% percentile of the
      SUV (SUV95) were more likely to develop symptomatic RP (P < .000012); each 0.1
      unit increase in SUV95 was associated with a 1.36-fold increase in the odds of
      symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted
      in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77),
      sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT
      imaging and dosimetric parameters were found to be poor predictors of RP
      symptoms. CONCLUSION: The SUV95, a biomarker of pretreatment pulmonary metabolic
      activity, was shown to be prognostic of symptomatic RP. Elevation in this
      pretreatment biomarker identifies patients at high risk for posttreatment
      symptomatic RP.

PMID- 25584708
TI  - Differentiation of Atypical Hepatocellular Carcinoma from Focal Nodular
      Hyperplasia: Diagnostic Performance of Contrast-enhanced US and Microflow
      Imaging.
AB  - PURPOSE: To evaluate diagnostic performance of contrast-enhanced (CE)
      ultrasonography (US) and microflow (MF) imaging in differentiation of atypical
      hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH). MATERIALS
      AND METHODS: Institutional review board approval was obtained, and informed
      consent was waived. A total of 103 patients (mean age, 43.9 years; age range, 17
      75 years) were included; 38 patients with HCC and 65 with FNH underwent CE US,
      and vascular architecture pattern (VAP) and arrival time parametric (ATP) images
      were analyzed. Resident and staff radiologists independently and retrospectively
      reviewed CE US, VAP, and ATP images. chi(2) test and logistic regression analysis
      were applied to identify specific features of FNH or HCC on CE US and MF images.
      To compare diagnostic performance of CE US with or without MF imaging, four sets
      of criteria were assigned: (a) routine CE US alone, (b) VAP and CE US, (c) ATP
      imaging and CE US, and (d) all three methods in combination. Sensitivity,
      specificity, accuracy, and area under the receiver operating characteristic curve
      (AUC) of resident and staff radiologists were analyzed. Cohen kappa statistic was
      used to assess agreement of CE US and MF imaging features between staff and
      resident radiologists. RESULTS: MF imaging offered significant improvements over
      most detection rates achieved with routine CE US signs in both groups. For staff
      radiologists, AUCs from criteria sets 3 (AUC = 0.873, P < .05) and 4 (AUC =
      0.887, P < .05) were significantly higher than AUC from criteria set 1 (AUC =
      0.835). For resident radiologists, specificity (71% and 69% vs 25%, P < .01) and
      accuracy (78% and 79% vs 50%, P < .01) of criteria sets 3 and 4 were
      significantly higher than those of criteria set 1. Moreover, AUCs for criteria
      sets 2 (AUC = 0.728, P < .05), 3 (AUC = 0.823, P < .01), and 4 (AUC = 0.857, P <
      .01) were significantly higher than those for criteria set 1 (AUC = 0.667).
      CONCLUSION: When compared with routine CE US, MF imaging can more effectively
      depict specific features and offers improved diagnostic performance in the
      differentiation of atypical HCC from FNH, especially when used by resident
      radiologists. Online supplemental material is available for this article.

PMID- 25584709
TI  - Three-way Comparison of Whole-Body MR, Coregistered Whole-Body FDG PET/MR, and
      Integrated Whole-Body FDG PET/CT Imaging: TNM and Stage Assessment Capability for
      Non-Small Cell Lung Cancer Patients.
AB  - PURPOSE: To prospectively compare the capabilities for TNM classification and
      assessment of clinical stage and operability among whole-body magnetic resonance
      (MR) imaging, coregistered positron emission tomographic (PET)/MR imaging with
      and without MR signal intensity (SI) assessment, and integrated fluorine 18
      fluorodeoxyglucose (FDG) PET/computed tomography (CT) in non-small cell lung
      cancer (NSCLC) patients. MATERIALS AND METHODS: The institutional review board
      approved this study, and written informed consent was obtained from each patient.
      One hundred forty consecutive NSCLC patients (75 men, 65 women; mean age, 72
      years) prospectively underwent whole-body MR imaging, FDG PET/CT, conventional
      radiologic examinations, and surgical, pathologic, and/or follow-up examinations.
      All factors and clinical stage and operability were then visually assessed. All
      PET/MR examinations were assessed with and without SI assessment. One examination
      used anatomic, metabolic, and relaxation-time information, and the other used
      only anatomic and metabolic information. kappa statistics were used for
      assessment of all factors and clinical stages with final diagnoses. McNemar test
      was used to compare the capability of all methods to assess operability. RESULTS:
      Agreements of assessment of every factor (kappa = 0.63-0.97) and clinical stage
      (kappa = 0.65-0.90) were substantial or almost perfect. Regarding capability to
      assess operability, accuracy of whole-body MR imaging and PET/MR imaging with SI
      assessment (97.1% [136 of 140]) was significantly higher than that of MR/PET
      without SI assessment and integrated FDG PET/CT (85.0% [119 of 140]; P < .001).
      CONCLUSION: Accuracies of whole-body MR imaging and PET/MR imaging with SI
      assessment are superior to PET/MR without SI assessment and PET/CT for
      identification of TNM factor, clinical stage, and operability evaluation of NSCLC
      patients.

PMID- 25584711
TI  - Extramammary Findings on Breast MR Examinations: Frequency, Clinical Relevance,
      and Patient Outcomes.
AB  - PURPOSE: To evaluate the frequency of extramammary findings on breast magnetic
      resonance (MR) images, recommendations for further imaging evaluation of each
      finding, and the subsequent effect on patient outcomes and health care
      expenditures. MATERIALS AND METHODS: Institutional review board approval was
      acquired for this HIPAA-compliant study. Informed consent was waived. Review of
      the institutional database identified 2324 breast MR examinations performed in
      women from January 1, 2010, to December 31, 2010. Breast MR imaging reports were
      reviewed for extramammary findings. Extramammary findings were categorized by
      using the computed tomography (CT) colonography reporting and data system (C
      RADS). The electronic medical record was reviewed for each patient with a C-RADS
      category E3 and E4 finding to assess clinical relevance and pathologic outcome.
      If an E3 or E4 finding was previously described and evaluated, the finding was
      downgraded and assigned a final C-RADS E2 category. The cost of additional
      imaging was estimated by using the Medicare physician fee schedule. Statistical
      significance was assessed by using chi(2) statistics. A P value less than .05
      indicated statistical significance, and 95% exact confidence intervals (CIs) were
      constructed. RESULTS: Extramammary findings were identified in 391 of 2324 breast
      MR examinations (16.8%), which included 105 patients (4.5%) with E3 or E4
      findings. Of the 2324 patients, 86 patients (3.7% [95% CI: 3.0%, 4.5%]) were
      recommended to undergo further imaging. After undergoing evaluation for
      additional imaging, a clinically important finding was found in nine patients
      (0.4% [95% CI: 0.2%, 0.7%]). Most frequently, hepatic lesions were the indication
      for additional imaging. Abdominal MR examinations accounted for 55% of costs
      related to additional imaging. Averaged across the entire cohort, further imaging
      evaluation and follow-up of incidental findings contributed an additional $16 to
      each breast MR imaging performed. CONCLUSION: Additional imaging evaluation for
      E3 and E4 extramammary findings at breast MR imaging can identify clinically
      important disease without substantially increasing cost. .

PMID- 25584710
TI  - Relationship between Overall Survival of Patients with Non-Small Cell Lung Cancer
      and Whole-Body Metabolic Tumor Burden Seen on Postsurgical Fluorodeoxyglucose PET
      Images.
AB  - PURPOSE: To test the hypothesis that whole-body metabolic tumor burden (MTBWB) on
      postsurgical fluorodeoxyglucose (FDG) positron emission tomographic
      (PET)/computed tomographic (CT) images in patients with non-small cell lung
      cancer (NSCLC) is associated with their overall survival (OS). MATERIALS AND
      METHODS: The institutional review board approved this study and waived the
      requirement for obtaining informed consent. One hundred forty-two patients with
      NSCLC (69 men, 73 women; median age, 67.7 years) who underwent postsurgical FDG
      PET/CT were retrospectively reviewed. The whole-body metabolic tumor volume
      (MTVWB), whole-body total lesion glycolysis (TLGWB), and whole-body maximum
      standardized uptake value (SUVWBmax) were measured. OS served as the primary end
      point of the study. Kaplan-Meier curves and Cox regression were used to assess
      the association between PET/CT markers and OS. RESULTS: The interobserver
      variability was low, as demonstrated with intraclass correlation coefficients
      higher than 0.94 for SUVWBmax, MTVWB, and TLGWB. When compared with those with
      negative postsurgical FDG PET/CT findings, a significant decrease of OS was found
      in patients with the presence of FDG-avid tumor on the basis of both a log-rank
      test (P = .001) and a univariate Cox model (hazard ratio = 2.805, P = .001). In
      patients with FDG-avid tumor, there was a significant association between OS and
      ln MTVWB (P < .001), ln TLGWB (P < .001), and ln SUVWBmax (P < .010) in either
      univariate or multivariate analysis, after adjusting for patient age, sex, TNM
      restage, and therapy after postsurgical PET/CT studies. The OS differences
      between the groups dichotomized by the median value of MTVWB (11.54 mL, P =
      .004), TLGWB (32.38 mL, P < .001), or SUVWBmax (4.93, P = .023) were significant.
      CONCLUSION: MTBWB and tumor maximum standardized uptake at postsurgical FDG
      PET/CT are related to the patient's OS in NSCLC, independent of age, sex, TNM
      restaging, and therapy after postsurgical PET/CT studies.

PMID- 25584712
TI  - Gastric Carcinoma: Ex Vivo MR Imaging at 7.0 T-Correlation with Histopathologic
      Findings.
AB  - PURPOSE: To determine the imaging detail and diagnostic information that can be
      obtained at 7.0-T magnetic resonance (MR) imaging with a voxel volume of 9.5-14.0
      nL as a means of evaluating the depth of mural invasion by gastric carcinomas ex
      vivo. MATERIALS AND METHODS: This study was approved by the institutional review
      board, and written informed consent was obtained from each patient. Twenty
      gastric specimens containing 20 carcinomas were studied with a 7.0-T MR imaging
      system equipped with a four-channel surface coil. MR images were obtained with a
      50-60 * 25-30 mm field of view, a 512 * 256 matrix, and a 1.0-mm section
      thickness, resulting in a voxel volume of 0.0095-0.0140 mm(3) (9.5-14.0 nL). The
      signal intensity of the gastric wall layers, tumor tissue, and fibrosis was
      described as low, intermediate, or high by comparing it with the signal intensity
      of the muscularis propria. Depth of invasion initially was assessed by two
      reviewers independently and then by the two reviewers in consensus. MR images
      were compared with histopathologic findings. RESULTS: The 7.0-T T2-weighted MR
      images clearly depicted the normal gastric wall in all 20 specimens (100%) as
      consisting of seven layers, which clearly corresponded to the tissue layers of
      the gastric wall. These MR images enabled clear differentiation between tumor
      tissue and fibrosis. Reviewers disagreed on the depth of invasion at the initial
      reading in three (15%) of 20 specimens (between mucosa and submucosa in two
      specimens and between muscularis propria and subserosa and serosa in one
      specimen); however, in all 20 gastric carcinomas, the depth of invasion could be
      accurately determined on T2-weighted images after consensus interpretation.
      CONCLUSION: Ex vivo 7.0-T MR imaging enables clear delineation of the gastric
      wall layers and clear differentiation of tumor tissue from fibrosis and allows
      one to assess the depth of mural invasion by gastric carcinomas.

PMID- 25584713
TI  - Synthesis of heterodimer radionuclide nanoparticles for magnetic resonance and
      single-photon emission computed tomography dual-modality imaging.
AB  - We report a facile synthesis of bifunctional Fe3O4-Ag(125)I heterodimers for use
      as dual-modality imaging agents in magnetic resonance (MR) and single-photon
      emission computed tomography (SPECT). We introduced (125)I, which is a clinically
      used radioisotope, as a SPECT reporter, into Fe3O4-Ag heterodimer nanoparticles
      to provide a new type of bifunctional contrast agent for MRI and SPECT imaging. 

PMID- 25584714
TI  - A self-determination theory approach to adults' healthy body weight motivation: A
      longitudinal study focussing on food choices and recreational physical activity.
AB  - This study focuses on body weight motivation based on self-determination theory.
      The impact of body weight motivation on longitudinal changes in food choices,
      recreational physical activity and body mass index was explored. A sample of
      adults (N = 2917, 47% men), randomly selected from the telephone book, completed
      a questionnaire in two consecutive years (2012, 2013), self-reporting food
      choices, recreational physical activity and body weight motivation. Types of body
      weight motivation at T1 (autonomous regulation, introjected regulation, and
      external regulation) were tested with regard to their predictive potential for
      changes in food choices, recreational physical activity and body mass index
      (BMI). Autonomous motivation predicted improvements in food choices and long-term
      adherence to vigorous recreational physical activity in both genders. Introjected
      motivation predicted long-term adherence to vigorous recreational physical
      activity only in women. External motivation predicted negative changes in food
      choices; however, the type of body weight motivation had no impact on BMI in
      overweight adults in the long term. Autonomous goal-setting regarding body weight
      seems to be substantial for healthy food choices and adherence to recreational
      physical activity. 

PMID- 25584715
TI  - Simultaneous electrochemical analysis of hydrophilic and lipophilic antioxidants
      in bicontinuous microemulsion.
AB  - Qualitative and quantitative analyses of hydrophilic and lipophilic antioxidants,
      such as polyphenols, by simple electrochemical measurements were conducted in a
      bicontinuous microemulsion (BME), in which water and oil phases coexisted
      bicontinuously on a microscopic scale. Hydrophilic and lipophilic antioxidants
      were individually monitored in the same BME solution using a hydrophilic indium
      tin oxide (ITO) electrode and a lipophilic fluorinated nanocarbon film electrode
      (F-ECR), respectively. The combination of well-balanced BME and extremely biased
      electrodes, such as ITO and F-ECR, in terms of hydrophilic-lipophilic balance
      allowed us to achieve individual monitoring of hydrophilic and lipophilic
      antioxidants in the same BME solution without extraction. Furthermore, the
      antioxidant activities of functional liquid foods, such as coffee and olive oil,
      were also evaluated by means of electrochemical measurements in BME solutions
      containing analytes in concentrations of several percent. The technique we
      propose provides a very simple, rapid, easily serviceable, and highly
      reproducible analysis and can be extended to a wide range of analytes and media. 

PMID- 25584716
TI  - Asthma and the hygiene hypothesis. Does cleanliness matter?
AB  - RATIONALE: The early hygiene hypothesis explained the development of allergies by
      a lack of infections; nowadays, the aspect of excessive cleanliness in affluent
      populations seems to have replaced this concept. Yet, no investigation has shown
      that home or personal cleanliness relate to allergic diseases. OBJECTIVES: To
      relate personal and home cleanliness to risk of asthma and allergies. METHODS:
      Comprehensive questionnaire information on home or personal cleanliness and
      allergic health conditions at school age was collected in 399 participants of the
      urban Perinatale Asthma Umwelt Langzeit Allergie Studie (PAULA) birth cohort.
      Bacterial markers were assessed in floor and mattress dust and were related to
      cleanliness and allergic diseases. MEASUREMENTS AND MAIN RESULTS: Personal
      cleanliness was inversely related to bacterial compounds on floors and
      mattresses, whereas home cleanliness effectively reduced dust amount but not
      microbial markers. Exposure to muramic acid related to a lower prevalence of
      school-age asthma (adjusted odds ratio, 0.59 [95% confidence interval, 0.39;
      0.90]). Mattress endotoxin in the first year of life was inversely associated
      with atopic sensitization (0.73 [0.56-0.96]) and asthma at school age (0.72 [0.55
      0.95]). Despite the associations of dust parameters both with cleanliness and
      allergic health conditions, the development of allergies was not related to home
      and personal cleanliness. CONCLUSIONS: Bacterial exposure in house dust
      determined childhood asthma and allergies. Personal cleanliness, such as washing
      hands, and home cleanliness were objectively reflected by dust parameters in
      homes. However, neither personal nor home cleanliness was associated with a risk
      for asthma and allergies. Other microbial components in house dust not affected
      by personal hygiene are likely to play a role.

PMID- 25584718
TI  - Clinical challenges of thyroid eye disease in HIV-positive patients on highly
      active antiretroviral therapy.
AB  - BACKGROUND: Graves' disease (GD) as an immune reconstitution inflammatory
      syndrome during highly active antiretroviral therapy (HAART) for HIV has
      previously been reported. However, clinical challenges associated with HIV in the
      context of thyroid eye disease (TED) are not as well-characterized. OBJECTIVE: To
      determine the frequency of coexisting HIV and TED, describe TED presentation and
      course in the context of HIV, and evaluate management difficulties as well as
      potential solutions. METHODS: Cross-sectional study of all patients with
      coexisting GD and HIV at University Hospitals Birmingham (2003-2014).
      Retrospective case note review to identify TED with particular reference to HAART
      regimen, CD4+ T-cell count, HIV viral load, and TED activity and severity.
      RESULTS: Of 783 subjects with GD and 1186 with HIV, 11 were identified with both
      GD and HIV. Of these, three had clinical features of TED; each was of Afro
      Caribbean origin, was in their fourth decade, and initially presented with
      undetectable CD4 T cells and high HIV viral loads. All went on to develop GD >3
      years after commencing HAART, with normal CD4 count and undetectable viral load
      at the time of GD diagnosis. The full spectrum of TED was represented, with two
      subjects requiring orbital decompression surgery. DISCUSSION: TED in the context
      of HIV is uncommon. Many challenges exist in such patients, particularly HAART
      drug interactions with antithyroid and immunosuppressant medications. To better
      understand TED in HIV and to counsel patients with this copathology most
      effectively, future multicenter surveillance is required.

PMID- 25584717
TI  - Variation in PPARG is associated with longitudinal change in insulin resistance
      in Mexican Americans at risk for type 2 diabetes.
AB  - CONTEXT: Peroxisome proliferator-activated receptor gamma (PPARG) is a
      susceptibility locus for type 2 diabetes mellitus (T2DM). Although cross
      sectional associations have been reported, primarily for Pro12Ala, few
      longitudinal studies in nondiabetic populations have been conducted. OBJECTIVE:
      This study aimed to examine whether and to what extent variation in PPARG is
      associated with longitudinal changes in anthropometric and metabolic traits in
      Mexican Americans at risk for T2DM. SETTING AND DESIGN: Subjects were
      participants of BetaGene, a family-based study of obesity, insulin resistance,
      and beta-cell function, who completed a baseline and follow-up study visit (n =
      378; mean followup, 4.6 +/- 1.5 y). Phenotypes included body fat assessed by dual
      energy x-ray absorptiometry; insulin sensitivity (SI), acute insulin response,
      and beta-cell function (disposition index; DI) were estimated from iv glucose
      tolerance tests with Minimal Model analysis. Eighteen tag single nucleotide
      polymorphisms (SNPs) capturing variation in a 156-kb region surrounding PPARG
      were tested for association with changes in longitudinal traits. P-values were
      Bonferroni-corrected for multiple testing. RESULTS: Six SNPs (rs2972164,
      rs11128598, rs17793951, rs1151996, rs1175541, rs3856806) were significantly
      associated with rate of change in SI after adjustment for age, sex, and body fat
      percentage, but not with changes in adiposity. rs17793951 also had a significant
      effect on change in DI over time. Association between rs1175541 and change in SI
      varied by changes in adiposity such that only carriers of the minor allele who
      reduced body fat over followup improved SI. rs1306470 (captured Pro12Ala, r(2) =
      0.9) was not associated with rates of change in any traits and its effects were
      not modified by changes in adiposity. CONCLUSIONS: Variation in PPARG, but not
      Pro12Ala, contributes to declining SI and concomitant deterioration in beta-cell
      function in Mexican Americans at risk for T2DM.

PMID- 25584719
TI  - Association of TERT promoter mutation 1,295,228 C>T with BRAF V600E mutation,
      older patient age, and distant metastasis in anaplastic thyroid cancer.
AB  - CONTEXT: The aggressive role of TERT promoter mutations has been well established
      in differentiated thyroid cancer but has not been established in anaplastic
      thyroid cancer (ATC). RESEARCH DESIGN: We tested the mutation status by
      sequencing genomic tumor DNA and examined its relationship with
      clinicopathological characteristics of ATC. RESULTS: Among 106 American and
      Chinese ATC samples, TERT 1,295,228 C>T (termed TERT C228T) mutation was found in
      37 (34.9%) cases, TERT promoter mutation 1,295,250 C>T was found in four cases
      (3.8%), and the two mutations were mutually exclusive and collectively found in
      41 cases (38.7%). TERT C228T occurred in 28 of 90 (31.1%) wild-type BRAF cases vs
      nine of 16 (56.3%) BRAF V600E cases, with an odds ratio of 2.85 (95% confidence
      interval, 0.96-8.42; P = .05). Patient age was 67.6 +/- 13.6 vs 61.6 +/- 11.4
      years in the TERT C228T vs wild-type TERT patients (P = .02), demonstrating an
      association between TERT C228T and older patient age. This association was also
      seen within the American cohort. In this cohort, which had more available
      clinicopathological data, TERT C228T was associated with distant metastasis of
      the tumor; specifically, distant metastasis occurred in 15 of 18 (83.3%) TERT
      C228T patients vs eight of 26 (30.8%) wild-type TERT patients, with an odds ratio
      of 11.25 (95% confidence interval, 2.53-50.08; P = .001). No association was
      found with patient sex, tumor size, lymph node metastasis, and extrathyroidal
      invasion of ATC. CONCLUSIONS: This is the largest study on the aggressive role of
      TERT promoter mutations in ATC, demonstrating an association of TERT C228T with
      BRAF V600E, older patient age, and tumor distant metastasis in ATC.

PMID- 25584721
TI  - How task complexity and stimulus modality affect motor execution: target
      accuracy, response timing and hesitations.
AB  - Elite sports players are characterized by the ability to produce successful
      outcomes while attending to changing environmental conditions. Few studies have
      assessed whether the perceptual environment affects motor skill execution. To
      test the effect of changing task complexity and stimulus conditions, the authors
      examined response times and target accuracy of 12 elite Australian football
      players using a passing-based laboratory test. Data were assessed using mixed
      modeling and chi-square analyses. No differences were found in target accuracy
      for changes in complexity or stimulus condition. Decision, movement and total
      disposal time increased with complexity and decision hesitations were greater
      when distractions were present. Decision, movement and disposal time were faster
      for auditory in comparison to visual signals, and when free to choose, players
      passed more frequently to auditory rather than visual targets. These results
      provide perspective on how basic motor control processes such as reaction and
      response to stimuli are influenced in a complex motor skill. Findings suggest
      auditory stimuli should be included in decision-making studies and may be an
      important part of a decision-training environment. 

PMID- 25584722
TI  - Impact of backpack type on respiratory muscle strength and lung function in
      children.
AB  - We examine the influence of backpack type on lung function and respiratory muscle
      strength in children. Thirty-seven children were assessed for lung function and
      inspiratory and expiratory muscle strength under four randomly determined
      conditions: unloaded erect standing and three conditions carrying 15% of the
      child's body weight. In these three conditions, children carried the weight on a
      backpack with bilateral shoulder straps carried over both shoulders, on a
      backpack with bilateral shoulder straps carried over one shoulder and on a
      backpack with a mono shoulder strap. Significantly lower forced vital capacity,
      forced expiratory volume in one second and maximal expiratory pressure were
      observed when children carried a backpack with a mono shoulder strap compared to
      the unloaded standing position. In conclusion, the restrictive effect and the
      decrease in expiratory muscle strength were more pronounced for the backpack with
      a mono shoulder strap, suggesting that a double strap backpack is preferable to a
      mono shoulder strap backpack. Practitioner summary: There is little known about
      the effect of schoolbags on respiratory muscle function. We investigated the
      influence of backpack type on lung function and respiratory muscle strength. A
      backpack with a mono shoulder strap created a restrictive effect and a decrease
      in strength, suggesting that a double strap backpack is preferable to a mono
      shoulder strap backpack. 

PMID- 25584720
TI  - Endogenous testosterone and its relationship to preclinical and clinical measures
      of cardiovascular disease in the atherosclerosis risk in communities study.
AB  - CONTEXT: Epidemiologic studies suggest that endogenous testosterone (T) levels in
      males may be implicated in cardiovascular disease (CVD), however further
      clarification is needed. OBJECTIVE: We assessed the cross-sectional relationship
      between endogenous plasma T and mean carotid intima media thickness (cIMT), and
      the longitudinal relationship with incident clinical CVD events, cardiac
      mortality, and all-cause mortality using male participants in the Atherosclerosis
      Risk in Communities (ARIC) study. DESIGN: This study involved a subset of men
      from visit 4 of the ARIC study. SETTING: The study was conducted in a community
      based cohort. PARTICIPANTS: Males who provided a morning blood sample excluding
      those taking androgen therapy, with prevalent coronary heart disease (CHD),
      stroke, or heart failure (HF) (n = 1558). INTERVENTION: None. MAIN OUTCOME
      MEASURES: Plasma T by liquid chromatography mass spectrometry and carotid IMT
      using high resolution B-mode ultrasound were obtained at visit 4. Incident CHD,
      HF, cardiac mortality, and all-cause mortality were identified by surveillance
      through 2010 (median 12.8 years). RESULTS: Lower T was significantly associated
      with higher body mass index, greater waist circumference, diabetes, hypertension,
      lower HDL, and never smoking (P = 0.01). T was not associated with mean cIMT in
      unadjusted or adjusted analyses. Following multivariable adjustment, there was no
      association of quartile (Q) of T with incident CHD [hazard ratio (HR) = 0.87 (95%
      CI = 0.60-1.26) for Q1; 0.97 (95% CI = 0.69-1.38) for Q2; 0.97 (95% CI = 0.69
      1.36) for Q3 compared to reference of Q4] or for incident HF [HR = 0.77 (95% CI =
      0.46-1.29) for Q1; 0.72 (95% CI = 0.43-1.21) for Q2; 0.87 (95% CI = 0.53-1.42)
      for Q3 compared to reference of Q4]. Similarly there was no association of Q of T
      with mortality or cardiac-associated mortality. CONCLUSIONS: Low male plasma T is
      cross-sectionally associated with key CVD risk factors, but after adjustment
      there was no association with mean cIMT, incident cardiac events, or mortality.
      Our results are reassuring that neither high nor low T levels directly predict
      atherosclerosis, but are a marker for other cardiovascular risk factors.

PMID- 25584723
TI  - 14-3-3 proteins in plant-pathogen interactions.
AB  - 14-3-3 proteins define a eukaryotic-specific protein family with a general role
      in signal transduction. Primarily, 14-3-3 proteins act as phosphosensors, binding
      phosphorylated client proteins and modulating their functions. Since
      phosphorylation regulates a plethora of different physiological responses in
      plants, 14-3-3 proteins play roles in multiple signaling pathways, including
      those controlling metabolism, hormone signaling, cell division, and responses to
      abiotic and biotic stimuli. Increasing evidence supports a prominent role of 14-3
      3 proteins in regulating plant immunity against pathogens at various levels. In
      this review, potential links between 14-3-3 function and the regulation of plant
      pathogen interactions are discussed, with a special focus on the regulation of 14
      3-3 proteins in response to pathogen perception, interactions between 14-3-3
      proteins and defense-related proteins, and 14-3-3 proteins as targets of pathogen
      effectors. 

PMID- 25584725
TI  - How are important life events disclosed on facebook? Relationships with
      likelihood of sharing and privacy.
AB  - This study examined an aspect of Facebook disclosure that has as yet gone
      unexplored: whether a user prefers to share information directly, for example,
      through status updates, or indirectly, via photos with no caption or relationship
      status changes without context or explanation. The focus was on the sharing of
      important positive and negative life events related to romantic relationships,
      health, and work/school in relation to likelihood of sharing this type of
      information on Facebook and general attitudes toward privacy. An online survey of
      599 adult Facebook users found that when positive life events were shared, users
      preferred to do so indirectly, whereas negative life events were more likely to
      be disclosed directly. Privacy shared little association with how information was
      shared. Implications for understanding the finer nuances of how news is shared on
      Facebook are discussed.

PMID- 25584724
TI  - Salicylic Acid Inhibits the Replication of Tomato bushy stunt virus by Directly
      Targeting a Host Component in the Replication Complex.
AB  - Although the plant hormone salicylic acid (SA) plays a central role in signaling
      resistance to viral infection, the underlying mechanisms are only partially
      understood. Identification and characterization of SA's direct targets have been
      shown to be an effective strategy for dissecting the complex SA-mediated defense
      signaling network. In search of additional SA targets, we previously developed
      two sensitive approaches that utilize SA analogs in conjunction with either a
      photoaffinity labeling technique or surface plasmon resonance-based technology to
      identify and evaluate candidate SA-binding proteins (SABPs) from Arabidopsis.
      Using these approaches, we have now identified several members of the Arabidopsis
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein family, including two
      chloroplast-localized and two cytosolic isoforms, as SABPs. Cytosolic GAPDH is a
      well-known glycolytic enzyme; it also is an important host factor involved in the
      replication of Tomato bushy stunt virus (TBSV), a single-stranded RNA virus.
      Using a yeast cell-free extract, an in vivo yeast replication system, and plant
      protoplasts, we demonstrate that SA inhibits TBSV replication. SA does so by
      inhibiting the binding of cytosolic GAPDH to the negative (-)RNA strand of TBSV.
      Thus, this study reveals a novel molecular mechanism through which SA regulates
      virus replication. 

PMID- 25584726
TI  - Couldn't or wouldn't? The influence of privacy concerns and self-efficacy in
      privacy management on privacy protection.
AB  - Sampling 515 college students, this study investigates how privacy protection,
      including profile visibility, self-disclosure, and friending, are influenced by
      privacy concerns and efficacy regarding one's own ability to manage privacy
      settings, a factor that researchers have yet to give a great deal of attention to
      in the context of social networking sites (SNSs). The results of this study
      indicate an inconsistency in adopting strategies to protect privacy, a disconnect
      from limiting profile visibility and friending to self-disclosure. More
      specifically, privacy concerns lead SNS users to limit their profile visibility
      and discourage them from expanding their network. However, they do not constrain
      self-disclosure. Similarly, while self-efficacy in privacy management encourages
      SNS users to limit their profile visibility, it facilitates self-disclosure. This
      suggests that if users are limiting their profile visibility and constraining
      their friending behaviors, it does not necessarily mean they will reduce self
      disclosure on SNSs because these behaviors are predicted by different factors. In
      addition, the study finds an interaction effect between privacy concerns and self
      efficacy in privacy management on friending. It points to the potential problem
      of increased risk-taking behaviors resulting from high self-efficacy in privacy
      management and low privacy concerns.

PMID- 25584727
TI  - Attitudes toward a game-based approach to mental health.
AB  - Based on preliminary research, game-based treatments appear to be a promising
      approach to post-traumatic stress disorder (PTSD). However, attitudes toward this
      novel approach must be better understood. Thus, the objective of this study was
      to determine if video game self-efficacy mediates the relationship between
      expectations and reactions to a game-based treatment for PTSD. Participants
      played the serious game "Walk in My Shoes" (Novonics Corp., Orlando, FL) and
      completed a series of scales to measure attitudes toward the intervention. Video
      game self-efficacy was found to be a partial mediator of expectancies and
      reactions. These results suggest that enhancing attitudes via self-efficacy in a
      clinical setting may maximize treatment effectiveness.

PMID- 25584728
TI  - Video game addiction and college performance among males: results from a 1 year
      longitudinal study.
AB  - This study explored the pattern of video game usage and video game addiction
      among male college students and examined how video game addiction was related to
      expectations of college engagement, college grade point average (GPA), and on
      campus drug and alcohol violations. Participants were 477 male, first year
      students at a liberal arts college. In the week before the start of classes,
      participants were given two surveys: one of expected college engagement, and the
      second of video game usage, including a measure of video game addiction. Results
      suggested that video game addiction is (a) negatively correlated with expected
      college engagement, (b) negatively correlated with college GPA, even when
      controlling for high school GPA, and (c) negatively correlated with drug and
      alcohol violations that occurred during the first year in college. Results are
      discussed in terms of implications for male students' engagement and success in
      college, and in terms of the construct validity of video game addiction.

PMID- 25584729
TI  - Effects of body image on college students' attitudes toward diet/fitness apps on
      smartphones.
AB  - Considering the increasing use of diet/fitness apps, this study aimed to
      investigate how four factors related to body image--evaluations of and
      orientations toward both appearance and fitness--impact college students'
      perception of the usefulness of such apps. Based on the Technology Acceptance
      Model, this study tested a path model examining the relationships among the four
      body-image-oriented factors, perceived usefulness (PU) of diet/fitness apps, and
      behavioral intention to use such apps. Results from a path analysis revealed that
      while college students' evaluation of appearance and fitness decreased the PU of
      diet/fitness apps, their orientation toward fitness increased the same outcome
      variable.

PMID- 25584730
TI  - Does a meditation protocol supported by a mobile application help people reduce
      stress? Suggestions from a controlled pragmatic trial.
AB  - The aim of this study was to examine the efficacy of a 3 week mindfulness
      inspired protocol, delivered by an Android application for smartphones, in
      reducing stress in the adult population. By using a controlled pragmatic trial, a
      self-help intervention group of meditators was compared with a typical control
      group listening to relaxing music and a waiting list group. The final sample
      included 56 Italian workers as participants, block randomized to the three
      conditions. The self-reported level of perceived stress was assessed at the
      beginning and at the end of the protocol. Participants were also instructed to
      track their heart rate before and after each session. The results did not show
      any significant differences between groups, but both self-help intervention
      groups demonstrated an improvement in coping with stress. Nevertheless,
      meditators and music listeners reported a significant decrease in average
      heartbeats per minute after each session. Furthermore, both groups perceived a
      moderate but significant change in stress reduction perceptions, even if with
      some peculiarities. Limitations and opportunities related to the meditation
      protocol supported by the mobile application to reduce stress are discussed.

PMID- 25584733
TI  - Surface developmental dyslexia is as prevalent as phonological dyslexia when
      appropriate control groups are employed.
AB  - Previous investigations of the incidence of developmental surface and
      phonological dyslexia using reading-age-matched control groups have identified
      many more phonological dyslexics (poor nonword reading relative to irregular-word
      reading) than surface dyslexics (poor irregular-word reading relative to nonword
      reading). However, because the measures that have been used to estimate reading
      age include irregular-word reading ability, they appear inappropriate for
      assessing the incidence of surface dyslexia. The current study used a novel
      method for generating control groups whose reading ability was matched to that of
      the dyslexic sample. The incidence of surface dyslexia was assessed by comparing
      dyslexic performance with that of a control group who were matched with the
      dyslexics on a test of nonword reading. The incidence of phonological dyslexia
      was assessed with reference to a control group who were matched with the
      dyslexics at irregular-word reading. These control groups led to the
      identification of an approximately equal number of children with surface and
      phonological dyslexia. It appeared that selecting control participants who were
      matched with dyslexics for reading age led to the recruitment of individuals with
      relatively high nonword reading scores relative to their irregular-word reading
      scores compared with other types of control group. The theoretical implications
      of these findings are discussed. 

PMID- 25584734
TI  - Support for distinct subcomponents of spatial working memory: a double
      dissociation between spatial-simultaneous and spatial-sequential performance in
      unilateral neglect.
AB  - Over the last decade, many studies have demonstrated that visuospatial working
      memory (VSWM) can be divided into separate subsystems dedicated to the retention
      of visual patterns and their serial order. Impaired VSWM has been suggested to
      exacerbate left visual neglect in right-brain-damaged individuals. The aim of
      this study was to investigate the segregation between spatial-sequential and
      spatial-simultaneous working memory in individuals with neglect. We demonstrated
      that patterns of results on these VSWM tasks can be dissociated. Spatial
      simultaneous and sequential aspects of VSWM can be selectively impaired in
      unilateral neglect. Our results support the hypothesis of multiple VSWM
      subsystems, which should be taken into account to better understand neglect
      related deficits. 

PMID- 25584735
TI  - Endovascular sac sealing concept: will the Endologix NellixTM device solve the
      deficiencies?
AB  - The deficiencies in current endovascular aneurysm repair include limited
      applicability to treat aneurysm anatomies, a significant reintervention rate to
      manage postprocedural complications and a requirement for postprocedural
      surveillance. Endovascular aneurysm sealing with the NellixTM device offers the
      potential to address these issues by directly treating the aneurysm sac and
      minimizing the risk of endoleak of any type as well as device migration. The
      unique sealing technology of polymer filled endobags also provides an opportunity
      to treat aneurysm anatomies that could not be effectively treated with
      conventional endografts. The early clinical experience with NellixTM supports
      these concepts but long-term durability is yet to be established. 

PMID- 25584737
TI  - Subclinical thyroid disorders.
AB  - Symptoms of the menopause transition-altered cycle length, change in amount of
      bleeding, sleep disruption, fatigue, mood swings, forgetfulness, heat
      intolerance, and palpitations-can also reflect thyroid dysfunction, common in
      midlife women. Although many clinicians are familiar with diagnosis and
      management of overt thyroid disorders, subclinical thyroid disease adds an
      entirely new dimension to this arena. 

PMID- 25584738
TI  - Breast arterial calcification and cardiovascular risk.

PMID- 25584739
TI  - Coffee or caffeine intake and effects on menopausal symptoms: unsolved issue.

PMID- 25584736
TI  - Bile acids as metabolic regulators.
AB  - PURPOSE OF REVIEW: This review focuses on the latest understanding of the
      molecular mechanisms underlying the complex interactions between intestine and
      liver bile acid signaling, gut microbiota, and their impact on whole-body lipid,
      glucose and energy metabolism. RECENT FINDINGS: Hepatic bile acid synthesis is
      tightly regulated by the bile acid negative feedback mechanisms. Modulating the
      enterohepatic bile acid signaling greatly impacts the whole-body metabolic
      homeostasis. Recently, a positive feedback mechanism through intestine farnesoid
      X receptor (FXR) antagonism has been proposed to link gut microbiota to the
      regulation of bile acid composition and pool size. Two studies identified
      intestine Diet1 and hepatic SHP-2 as novel regulators of CYP7A1 and bile acid
      synthesis through the gut-liver FXR-fibroblast growth factor 15/19-FGF receptor
      four signaling axis. New evidence suggests that enhancing bile acid signaling in
      the distal ileum and colon contributes to the metabolic benefits of bile acid
      sequestrants and bariatric surgery. SUMMARY: Small-molecule ligands that target
      TGR5 and FXR have shown promise in treating various metabolic and inflammation
      related human diseases. New insights into the mechanisms underlying the bariatric
      surgery and bile acid sequestrant treatment suggest that targeting the
      enterohepatic circulation to modulate gut-liver bile acid signaling, incretin
      production and microbiota represents a new strategy to treat obesity and type 2
      diabetes.

PMID- 25584740
TI  - How old is too old for hormone therapy?

PMID- 25584742
TI  - Degrading Claspin away with Cdh1 and Cyclin A.

PMID- 25584741
TI  - Therapeutic potential of gingival fibroblasts for cutaneous radiation syndrome:
      comparison to bone marrow-mesenchymal stem cell grafts.
AB  - Mesenchymal stem cell (MSC) therapy has recently been investigated as a potential
      treatment for cutaneous radiation burns. We tested the hypothesis that injection
      of local gingival fibroblasts (GFs) would promote healing of radiation burn
      lesions and compared results with those for MSC transplantation. Human clinical-
      grade GFs or bone marrow-derived MSCs were intradermally injected into mice 21
      days after local leg irradiation. Immunostaining and real-time PCR analysis were
      used to assess the effects of each treatment on extracellular matrix remodeling
      and inflammation in skin on days 28 and 50 postirradiation. GFs induced the early
      development of thick, fully regenerated epidermis, skin appendages, and hair
      follicles, earlier than MSCs did. The acceleration of wound healing by GFs
      involved rearrangement of the deposited collagen, modification of the
      Col/MMP/TIMP balance, and modulation of the expression and localization of
      tenascin-C and of the expression of growth factors (VEGF, EGF, and FGF7). As MSC
      treatment did, GF injection decreased the irradiation-induced inflammatory
      response and switched the differentiation of macrophages toward an M2-like
      phenotype, characterized by CD163(+) macrophage infiltration and strong
      expression of arginase-1. These findings indicate that GFs are an attractive
      target for regenerative medicine, for easier to collect, can grow in culture, and
      promote cutaneous wound healing in irradiation burn lesions. 

PMID- 25584745
TI  - Micro-nanostructured CuO/C spheres as high-performance anode materials for Na-ion
      batteries.
AB  - In this paper, we report on the synthesis of micro-nanostructured CuO/C spheres
      by aerosol spray pyrolysis and their application as high-performance anodes in
      sodium-ion batteries. Micro-nanostructured CuO/C spheres with different CuO
      contents were synthesized through aerosol spray pyrolysis by adjusting the ratio
      of reactants and heat-treated by an oxidation process. The as-prepared CuO/C
      spheres show uniformly spherical morphology, in which CuO nanoparticles (~10 nm)
      are homogeneously embedded in the carbon matrix (denoted as 10-CuO/C). The
      electrochemical performance of 10-CuO/C with a carbon weight of 44% was evaluated
      as the anode material for Na-ion batteries. It can deliver a capacity of 402 mA h
      g(-1) after 600 cycles at a current density of 200 mA g(-1). Furthermore, a
      capacity of 304 mA h g(-1) was obtained at a high current density of 2000 mA g(
      1). The superior electrochemical performance of the micro-nanostructured CuO/C
      spheres leads to the enhancement of the electronic conductivity of the
      nanocomposite and the accommodation of the volume variation of CuO/C during
      charge/discharge cycling. 

PMID- 25584744
TI  - Active ageing and quality of life: factors associated with participation in
      leisure activities among institutionalized older adults, with and without
      dementia.
AB  - OBJECTIVES: Active ageing, considered from the perspective of participation in
      leisure activities, promotes life satisfaction and personal well-being. The aims
      of this work are to define and explain leisure activity profiles among
      institutionalized older adults, considering their sociodemographic
      characteristics and objective and subjective conditions in relation to their
      quality of life. METHODS: Two samples of institutionalized people aged 60 and
      over were analysed together: 234 older adults without dementia and 525 with
      dementia. Sociodemographic, economic, family and social network, and health and
      functioning variables were selected. Cluster analysis was applied to obtain
      activity profiles according to the leisure activities, and ordinal regression
      models were performed to analyse factors associated to activity level. RESULTS:
      The sample was clustered into three groups of people: active (27%), moderately
      active (35%) and inactive people (38%). In the final regression model (Nagelkerke
      pseudo R(2) = 0.500), a higher level of activity was associated with better
      cognitive function (Pfeiffer scale), self-perceived health status and functional
      ability, as well as with a higher frequency of gathering with family and friends,
      and higher educational level. CONCLUSION: The decline in physical and mental
      health, the loss of functional capabilities and the weakening of family and
      social ties represent a significant barrier to active ageing in a context of
      institutionalization.

PMID- 25584766
TI  - Decreased hyaluronidase 1 expression is associated with early disease recurrence
      in human endometrial cancer.
AB  - OBJECTIVE: Hyaluronidases (HYAL1 and HYAL2) are key enzymes in the degradation of
      hyaluronan, and their expression has been altered in various cancer types. We
      previously showed that hyaluronan accumulation in endometrial carcinomas was
      correlated with decreased mRNA expression of the HYAL genes. In this study, we
      analyzed HYAL1 and HYAL2 protein expressions in normal and precancerous
      endometrial tissues and in endometrial carcinomas. We also investigated whether
      the protein levels were associated with clinicopathological factors, invasion,
      and disease recurrence. METHODS: A total of 343 tissue specimens from normal,
      atrophic, hypertrophic, and neoplastic endometria were analyzed
      immunohistochemically for HYAL1 and HYAL2 expressions. The results were
      correlated with clinicopathological factors, the expression of the epithelial
      mesenchymal transition marker, E-cadherin, and disease recurrence. RESULTS:
      Reduced HYAL1 expression was associated with the progression of endometrial
      carcinomas towards higher grades and also with large tumor sizes, lymph node
      metastasis, and lymphovascular invasion. Reduced expression of both HYAL1 and
      HYAL2 was associated with deep myometrial invasion. HYAL2 expression was
      primarily constant in neoplastic tissues, but its expression was altered in
      different phases of the endometrial cycle. In addition, a reduction in HYAL1
      expression was associated with the depletion of E-cadherin. In a multivariate
      analysis, reduced HYAL1 expression was an independent prognostic factor for early
      disease recurrence (HR 5.13, 95% CI: 1.131-23.270, p=0.034). CONCLUSIONS: This
      study showed that reduced HYAL1 expression was associated with endometrial
      carcinoma aggressiveness, which further supported the role of hyaluronan
      degradation in cancer progression.

PMID- 25584769
TI  - Microwave-assisted synthesis of mesoporous Co3O4 nanoflakes for applications in
      lithium ion batteries and oxygen evolution reactions.
AB  - Mesoporous Co3O4 nanoflakes with an interconnected architecture were successfully
      synthesized using a microwave-assisted hydrothermal and low-temperature
      conversion method, which exhibited excellent electrochemical performances as
      anode materials in lithium ion batteries and as catalysts in the oxygen evolution
      reaction (OER). Field-emission scanning electron microscopy (FESEM) and
      transmission electron microscopy (TEM) observations showed the unique
      interconnected and mesoporous structure. When employed as anode materials for
      lithium ion batteries, mesoporous Co3O4 nanoflakes delivered a high specific
      capacity of 883 mAh/g at 0.1C current rate and stable cycling performances even
      at higher current rates. Post-mortem analysis of ex situ FESEM images revealed
      that the mesoporous and interconnected structure had been well maintained after
      long-term cycling. The mesoporous Co3O4 nanoflakes also showed both OER active
      properties and good catalytic stability. This could be attributed to both the
      stability of unique mesoporous structure and highly reactive facets. 

PMID- 25584768
TI  - Construction and characterization of 3A-epitope-tagged foot-and-mouth disease
      virus.
AB  - Nonstructural protein 3A of foot-and-mouth disease virus (FMDV) is a partially
      conserved protein of 153 amino acids (aa) in most FMDVs examined to date.
      Specific deletion in the FMDV 3A protein has been associated with the inability
      of FMDV to grow in primary bovine cells and cause disease in cattle. However, the
      aa residues playing key roles in these processes are poorly understood. In this
      study, we constructed epitope-tagged FMDVs containing an 8 aa FLAG epitope, a 9
      aa haemagglutinin (HA) epitope, and a 10 aa c-Myc epitope to substitute residues
      94-101, 93-101, and 93-102 of 3A protein, respectively, using a recently
      developed O/SEA/Mya-98 FMDV infectious cDNA clone. Immunofluorescence assay
      (IFA), Western blot and sequence analysis showed that the epitope-tagged viruses
      stably maintained and expressed the foreign epitopes even after 10 serial
      passages in BHK-21 cells. The epitope-tagged viruses displayed growth properties
      and plaque phenotypes similar to those of the parental virus in BHK-21 cells.
      However, the epitope-tagged viruses exhibited lower growth rates and smaller
      plaque size phenotypes than those of the parental virus in primary fetal bovine
      kidney (FBK) cells, but similar growth properties and plaque phenotypes to those
      of the recombinant viruses harboring 93-102 deletion in 3A. These results
      demonstrate that the decreased ability of FMDV to replicate in primary bovine
      cells was not associated with the length of 3A, and the genetic determinant
      thought to play key role in decreased ability to replicate in primary bovine
      cells could be reduced from 93-102 residues to 8 aa residues at positions 94-101
      in 3A protein. 

PMID- 25584743
TI  - Breath analysis as a potential and non-invasive frontier in disease diagnosis: an
      overview.
AB  - Currently, a small number of diseases, particularly cardiovascular (CVDs),
      oncologic (ODs), neurodegenerative (NDDs), chronic respiratory diseases, as well
      as diabetes, form a severe burden to most of the countries worldwide. Hence,
      there is an urgent need for development of efficient diagnostic tools,
      particularly those enabling reliable detection of diseases, at their early
      stages, preferably using non-invasive approaches. Breath analysis is a non
      invasive approach relying only on the characterisation of volatile composition of
      the exhaled breath (EB) that in turn reflects the volatile composition of the
      bloodstream and airways and therefore the status and condition of the whole
      organism metabolism. Advanced sampling procedures (solid-phase and needle traps
      microextraction) coupled with modern analytical technologies (proton transfer
      reaction mass spectrometry, selected ion flow tube mass spectrometry, ion
      mobility spectrometry, e-noses, etc.) allow the characterisation of EB
      composition to an unprecedented level. However, a key challenge in EB analysis is
      the proper statistical analysis and interpretation of the large and heterogeneous
      datasets obtained from EB research. There is no standard statistical
      framework/protocol yet available in literature that can be used for EB data
      analysis towards discovery of biomarkers for use in a typical clinical setup.
      Nevertheless, EB analysis has immense potential towards development of biomarkers
      for the early disease diagnosis of diseases. 

PMID- 25584770
TI  - Direct observation of graphene growth and associated copper substrate dynamics by
      in situ scanning electron microscopy.
AB  - This work highlights the importance of in situ experiments for an improved
      understanding of graphene growth on copper via metal-catalyzed chemical vapor
      deposition (CVD). Graphene growth inside the chamber of a modified environmental
      scanning electron microscope under relevant low-pressure CVD conditions allows
      visualizing structural dynamics of the active catalyst simultaneously with
      graphene nucleation and growth in an unparalleled way. It enables the observation
      of a complete CVD process from substrate annealing through graphene nucleation
      and growth and, finally, substrate cooling in real time and nanometer-scale
      resolution without the need of sample transfer. A strong dependence of surface
      dynamics such as sublimation and surface premelting on grain orientation is
      demonstrated, and the influence of substrate dynamics on graphene nucleation and
      growth is presented. Insights on the growth mechanism are provided by a
      simultaneous observation of the growth front propagation and nucleation rate.
      Furthermore, the role of trace amounts of oxygen during growth is discussed and
      related to graphene-induced surface reconstructions during cooling. Above all,
      this work demonstrates the potential of the method for in situ studies of surface
      dynamics on active metal catalysts. 

PMID- 25584771
TI  - Synthesis, structural characterization, and physical properties of the new
      transition metal oxyselenide Ce2O2ZnSe2.
AB  - The quaternary transition metal oxyselenide Ce2O2ZnSe2 has been shown to adopt a
      ZrCuSiAs-related structure with Zn(2+) cations in a new ordered arrangement
      within [ZnSe2](2-) layers. The color of the compound changes as a function of
      cell volume, which can vary by ~0.4% under different synthetic conditions. At the
      highest, intermediate, and lowest cell volumes, the color is yellow-ochre, brown,
      and black, respectively. The decreased volume is attributed to oxidation of Ce
      from 3+ to 4+, the extent of which can be controlled by synthetic conditions.
      Ce2O2ZnSe2 is a semiconductor at all cell volumes with experimental optical band
      gaps of 2.2, 1.4, and 1.3 eV for high, intermediate, and low cell volume samples,
      respectively. SQUID measurements show Ce2O2ZnSe2 to be paramagnetic from 2 to 300
      K with a negative Weiss temperature of theta = -10 K, suggesting weak
      antiferromagnetic interactions. 

PMID- 25584767
TI  - Basic science and clinical management of painful and non-painful chemotherapy
      related neuropathy.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of
      several chemotherapeutics used in the treatment of all the most common
      malignancies. There are several defined mechanisms of nerve damage that take
      place along different areas of the peripheral and the central nervous system.
      Treatment is based on symptom management and there are several classes of
      medications found to be efficacious in the treatment of neuropathic pain.
      Neuropathic pain that persists despite appropriate pharmacotherapy may respond to
      interventional procedures that span a range of invasiveness. The purpose of this
      review article is to examine the basic science of neuropathy and currently
      available treatment options in the context of chemotherapy induced peripheral
      neuropathy. 

PMID- 25584772
TI  - May non-antipsychotic drugs improve cognition of schizophrenia patients?
AB  - RATIONALE: Cognitive impairment in schizophrenia patients is associated with poor
      outcome and it represents one of main challenges of pharmacological treatment.
      Unfortunately, second-generation antipsychotics have not yielded the expected
      results in the improvement of these symptoms. OBJECTIVE: The purpose of the
      present review paper is to summarize and discuss the available data about the
      efficacy of non-antipsychotic drugs in the treatment of cognitive symptoms of
      schizophrenia. METHODS: A research in the main database sources has been
      performed to obtain a comprehensive overview. Studies with different
      methodologies (open and double-blinded) have been included, while studies with
      schizoaffective patients have been excluded. RESULTS: Several non-antipsychotic
      compounds have been tested with the purpose to improve cognitive symptoms in
      schizophrenia patients, but no molecule has a significant pro-cognitive activity.
      CONCLUSION: Available data do not support the superiority of non-antipsychotic
      drugs vs. placebo for cognitive enhancement in schizophrenia. Preliminary results
      indicate mirtazapine, mianserine, lamotrigine, tandospirone, cyproheptadine,
      valacyclovir and omega-3 fatty acids as the most promising compounds, however no
      definitive conclusions can be drawn in the light of small sample size studies.

PMID- 25584773
TI  - Clusters and inverse emulsions from nanoparticle surfactants in organic solvents.
AB  - A method is presented for the synthesis of self-assembling nanoparticle
      surfactants in nonpolar organic solvents. The method relies on the control of
      long-range steric repulsion imparted by grafted polystyrene and short-range
      attraction from short-chain thiol molecules with an alcohol or carboxylic
      functionality. Similar to water-based nanoparticle surfactants, these oil
      dispersed materials are found to cluster in dispersion and also to stabilize oil
      water interfaces to form water-in-oil emulsions. The clustering process is
      characterized with dynamic light scattering (DLS), small-angle X-ray scattering
      (SAXS), UV-vis spectroscopy, and transmission electron microscopy (TEM).
      Thermogravimetric analysis (TGA) is used to quantify the surface concentration of
      grafted polymer, which is found to be a parameter of critical importance for the
      formation of stable clusters. The clustering kinetics and dispersion stability
      are both affected by the polymer molecular weight, surface concentration, and
      chemical structure of the thiol molecules that induce particle attraction.
      Nanometer-sized water-in-oil emulsions are formed by sonication in the presence
      of nanoparticle surfactants. A large broadening of the optical absorption
      spectrum in the NIR region is observed because of changes in the collective
      surface plasmon resonance of the gold particle shell. 

PMID- 25584774
TI  - Endothelin-1 upregulation mediates aging-related cardiac fibrosis.
AB  - Endothelin-1 (ET-1) plays a major role in regulating myocardial fibrosis in
      several pathological conditions, such as hypertension and diabetes. Aging is an
      independent risk factor for myocardial fibrosis. We hypothesized that ET-1
      upregulation may be a basis of enhanced collagen synthesis in the senescent
      fibroblasts resulting in cardiac fibrosis with aging. To examine this hypothesis,
      we cultured mouse cardiac fibroblasts to passage-30 (P30). beta-Galactosidase
      activity and several other aging markers were markedly increased in P30 (vs. P3)
      fibroblasts, indicating that these cells were indeed undergoing senescence.
      Importantly, ET-1 expression was markedly upregulated in P30 (vs. P3)
      fibroblasts. Of note, estrogen receptor-alpha (ER-alpha), an important negative
      regulator of ET-1, was downregulated in P30 fibroblasts. We also studied aged
      (130-weeks old, female) mice hearts, and observed that ET-1 was upregulated and
      ER-alpha was downregulated in these hearts (vs. 6-week old mice hearts, female).
      Similar observations were made in the fibroblasts isolated from aged mice hearts.
      ET-1 upregulation with aging was also seen in ~70-year old (vs. ~30-year old)
      human heart sections. In concert with ET-1 upregulation, the expression of
      fibronectin and collagens was found to be markedly increased in P30 cardiac
      fibroblasts in culture, fibroblasts isolated from the aged mice hearts, and in
      aged human hearts. Interestingly, inhibition of ET-1 in the senescent P30
      fibroblasts by 2 different strategies (the use of siRNA and the use of endothelin
      converting enzyme inhibitors) markedly suppressed expression of fibrosis signals.
      Further, treatment with synthetic ET-1 enhanced fibronectin and collagen
      expression in P3 cardiac fibroblasts. These observations in mice and human hearts
      suggest that aging-related cardiac fibrosis is, at least partially, dependent on
      the upregulation of ET-1.

PMID- 25584775
TI  - Granulocyte-colony stimulating factor (G-CSF)-induced mechanical hyperalgesia in
      mice: Role for peripheral TNFalpha, IL-1beta and IL-10.
AB  - Granulocyte-colony stimulating factor (G-CSF) is a therapeutic approach to
      increase peripheral neutrophil counts after anti-tumor therapies. Pain is the
      major side effect of G-CSF. Intraplantar administration of G-CSF in mice induces
      mechanical hyperalgesia. However, the peripheral mechanisms involved in this
      effect were not elucidated. Therefore, the participation of pronociceptive
      cytokines tumor necrosis factor (TNF) alpha (TNFalpha), interleukin (IL)-1 beta
      (IL-1beta) and antinociceptive cytokine IL-10 in G-CSF-induced mechanical
      hyperalgesia in mice was investigated. G-CSF-induced mechanical hyperalgesia was
      inhibited by systemic and local treatment with etanercept and IL-1 receptor
      antagonist (IL-1ra) or TNF receptor 1 (TNFR1) deficiency and increased in IL-10
      deficient mice. In agreement, G-CSF injection induced significant TNFalpha, IL
      1beta and IL-10 production in paw tissue. G-CSF-induced hyperalgesia was dose
      dependently inhibited by thalidomide (5-45mg/kg) and pentoxifylline (0.5
      13.5mg/kg), and treatment with these drugs inhibited G-CSF-induced TNFalpha, IL
      1beta and IL-10 production. The combined treatment with pentoxifylline or
      thalidomide with morphine, at doses that are ineffective as single treatment,
      diminished G-CSF-induced hyperalgesia through inhibiting cytokine production.
      Indomethacin also reduces G-CSF hyperalgesia alone or combined with
      pentoxifylline or thalidomide. Thus, G-CSF-induced hyperalgesia might be mediate
      by peripheral production of pronociceptive cytokines TNFalpha and IL-1beta and
      down-regulated by IL-10. Systemic IL-1ra reduced G-CSF-induced increase of
      peripheral neutrophil counts. However, local treatment with morphine, IL-1ra or
      etanercept, and systemic treatment with indomethacin, etanercept, thalidomide and
      pentoxifylline did not alter G-CSF-induced mobilization of neutrophils.
      Therefore, this study advances in the understanding of G-CSF-induced hyperalgesia
      and suggests therapeutic approaches for its control. 

PMID- 25584776
TI  - Genetic identification and distribution of the parasitic larvae of Anisakis
      pegreffii and Anisakis simplex (s. s.) in European hake Merluccius merluccius
      from the Tyrrhenian Sea and Spanish Atlantic coast: implications for food safety.
AB  - The consumption of the hake Merluccius merluccius is widespread in European
      countries, where this fish has a high commercial value. To date, different larval
      species of Anisakis have been identified as parasites in M. merluccius from
      European waters, Anisakis pegreffii and Anisakis simplex (s. s.) being the two
      most common. The aim of the study is to present data on the occurrence of
      Anisakis spp. larvae in the viscera and flesh of M. merluccius. Consequently, the
      distribution and infection rates of different species of Anisakis in different
      sites (viscera, and dorsal and ventral fillets) were investigated in hake caught
      in the central Tyrrhenian Sea (FAO 37.1.3) and the NE Atlantic Ocean (FAO 27
      IXa). A sample of N=65 fish individuals (length>26 cm) was examined
      parasitologically from each fishing ground. The fillets were examined using the
      pepsin digestion method. A large number (1310) of Anisakis specimens were
      identified by multilocus allozyme electrophoresis (MAE) and mtDNA cox2 sequence
      analysis; among these, 814 larvae corresponded to A. simplex (s. s.) and 476 to
      A. pegreffii. They were found to infect both the flesh and the viscera. The two
      species co-infected the same individual fish (both in the viscera and in the
      flesh) from the FAO 27 area, whereas only A. pegreffii was found in hake from the
      Tyrrhenian Sea. The average parasite burden of A. pegreffii in hake from the
      Tyrrhenian Sea was significantly lower to that observed from hake off the
      Atlantic coast of Spain, both in prevalence and in abundance. In addition,
      whereas no significant difference in overall prevalence values was recorded
      between the two Anisakis species in the viscera of the FAO 27 sample, significant
      differences were found in the abundance levels observed between these species in
      the flesh, with A. simplex (s. s.) exhibiting significantly higher levels than
      that observed for A. pegreffii (p<0.001). Given that the pathogenic role in
      relation to man is known for these two species of Anisakis, both the flesh
      inspection and the infection rates of the different anisakid species assume
      particular importance in terms of assessing the risk they pose to humans.

PMID- 25584777
TI  - Pyrosequencing vs. culture-dependent approaches to analyze lactic acid bacteria
      associated to chicha, a traditional maize-based fermented beverage from
      Northwestern Argentina.
AB  - The diversity of lactic acid bacteria (LAB) associated with chicha, a traditional
      maize-based fermented alcoholic beverage from Northwestern Argentina, was
      analyzed using culture-dependent and culture-independent approaches. Samples
      corresponding to 10 production steps were obtained from two local producers at
      Maimara (chicha M) and Tumbaya (chicha T). Whereas by culture-dependent approach
      a few number of species (Lactobacillus plantarum and Weissella viridescens in
      chicha M, and Enterococcus faecium and Leuconostoc mesenteroides in chicha T)
      were identified, a higher quantitative distribution of taxa was found in both
      beverages by pyrosequencing. The relative abundance of OTUs was higher in chicha
      M than in chicha T; six LAB genera were common for chicha M and T: Enterococcus,
      Lactococcus, Streptococcus, Weissella, Leuconostoc and Lactobacillus while
      Pediococcus only was detected in chicha M. Among the 46 identified LAB species,
      those of Lactobacillus were dominant in both chicha samples, exhibiting the
      highest diversity, whereas Enterococcus and Leuconostoc were recorded as the
      second dominant genera in chicha T and M, respectively. Identification at species
      level showed the predominance of Lb. plantarum, Lactobacillus rossiae,
      Leuconostoc lactis and W. viridescens in chicha M while Enterococcus hirae, E.
      faecium, Lc. mesenteroides and Weissella confusa predominated in chicha T
      samples. In parallel, when presumptive LAB isolates (chicha M: 146; chicha T:
      246) recovered from the same samples were identified by ISR-PCR and RAPD-PCR
      profiles, species-specific PCR and 16S rRNA gene sequencing, most of them were
      assigned to the Leuconostoc genus (Lc. mesenteroides and Lc. lactis) in chicha M,
      Lactobacillus, Weissella and Enterococcus being also present. In contrast, chicha
      T exhibited the presence of Enterococcus and Leuconostoc, E. faecium being the
      most representative species. Massive sequencing approach was applied for the
      first time to study the diversity and evolution of microbial communities during
      chicha manufacture. Although differences in the LAB species profile between the
      two geographically different chicha productions were observed by culturing, a
      larger number for predominant LAB species as well as other minorities were
      revealed by pyrosequencing. The fine molecular inventory achieved by
      pyrosequencing provided more precise information on LAB population composition
      than culture-dependent analysis processes. 

PMID- 25584778
TI  - Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal
      cortex signalling molecules involved in recognition memory.
AB  - High fat (HF) diets are known to induce changes in synaptic plasticity in the
      forebrain leading to learning and memory impairments. Previous studies of
      oleanolic acid derivatives have found that these compounds can cross the blood
      brain barrier to prevent neuronal cell death. We examined the hypothesis that the
      oleanolic acid derivative, bardoxolone methyl (BM) would prevent diet-induced
      cognitive deficits in mice fed a HF diet. C57BL/6J male mice were fed a lab chow
      (LC) (5% of energy as fat), a HF (40% of energy as fat), or a HF diet
      supplemented with 10mg/kg/day BM orally for 21weeks. Recognition memory was
      assessed by performing a novel object recognition test on the treated mice.
      Downstream brain-derived neurotrophic factor (BDNF) signalling molecules were
      examined in the prefrontal cortex (PFC) and hippocampus of mice via Western
      blotting and N-methyl-d-aspartate (NMDA) receptor binding. BM treatment prevented
      HF diet-induced impairment in recognition memory (p<0.001). In HF diet fed mice,
      BM administration attenuated alterations in the NMDA receptor binding density in
      the PFC (p<0.05), however, no changes were seen in the hippocampus (p>0.05). In
      the PFC and hippocampus of the HF diet fed mice, BM administration improved
      downstream BDNF signalling as indicated by increased protein levels of BDNF,
      phosphorylated tropomyosin related kinase B (pTrkB) and phosphorylated protein
      kinase B (pAkt), and increased phosphorylated AMP-activated protein kinase
      (pAMPK) (p<0.05). BM administration also prevented the HF diet-induced increase
      in the protein levels of inflammatory molecules, phosphorylated c-Jun N-terminal
      kinase (pJNK) in the PFC, and protein tyrosine phosphatase 1B (PTP1B) in both the
      PFC and hippocampus. In summary, these findings suggest that BM prevents HF diet
      induced impairments in recognition memory by improving downstream BDNF signal
      transduction, increasing pAMPK, and reducing inflammation in the PFC and
      hippocampus. 

PMID- 25584779
TI  - Love is the triumph of the imagination: Daydreams about significant others are
      associated with increased happiness, love and connection.
AB  - Social relationships and interactions contribute to daily emotional well-being.
      The emotional benefits that come from engaging with others are known to arise
      from real events, but do they also come from the imagination during daydreaming
      activity? Using experience sampling methodology with 101 participants, we
      obtained 371 reports of naturally occurring daydreams with social and non-social
      content and self-reported feelings before and after daydreaming. Social, but not
      non-social, daydreams were associated with increased happiness, love and
      connection and this effect was not solely attributable to the emotional content
      of the daydreams. These effects were only present when participants were lacking
      in these feelings before daydreaming and when the daydream involved imagining
      others with whom the daydreamer had a high quality relationship. Findings are
      consistent with the idea that social daydreams may function to regulate emotion:
      imagining close others may serve the current emotional needs of daydreamers by
      increasing positive feelings towards themselves and others. 

PMID- 25584780
TI  - A matter of focus: Detailed memory in the intentional autobiographical recall of
      older and younger adults.
AB  - The intricately interwoven role of detailed autobiographical memory in our daily
      lives and in our imaginative envisioning of the future is increasingly
      recognized. But how is the detail-rich nature of autobiographical memory best
      assessed and, in particular, how can possible aging-related differences in
      autobiographical memory specificity be most effectively evaluated? This study
      examined whether a modified interview, involving fewer and time-matched events
      for older and younger adults, yielded age-related outcomes similar to those that
      have been previously reported. As in earlier studies, modest age-related changes
      in the specificity of autobiographical recall were observed, yet the largest most
      robust effect for both age groups was the substantial proportion of specific
      details retrieved. Both age groups rated recent memories as significantly less
      important and as less emotional than more temporally distant events. Our findings
      counter conceptions of older adults' autobiographical memories as invariably less
      episodically rich than those of younger adults. 

PMID- 25584782
TI  - Synthesis of two subunits of the macrolide domain of the immunosuppressive agent
      sanglifehrin a and assembly of a macrolactone precursor. application of masamune
      anti-aldol condensation.
AB  - Asymmetric anti-aldol coupling of a norephedrine-derived ester with an alpha
      chiral aldehyde was used to synthesize a carboxylic acid representing the C13-C19
      segment of the macrocyclic domain present in the immunosuppressive agent
      sanglifehrin A. Felkin addition set configuration at the C14-C17 stereotetrad in
      this unit in which hydroxyl functions at C15 and C17 were masked as an internal
      ketal. The carboxyl group of this segment was coupled to the N-terminus of the
      tripeptide portion (C1-N12) of sanglifehrin A macrolactone to assemble the C1-C19
      domain. Synthesis of the C20-C25 subunit of sanglifehrin A containing a (23S)
      alcohol was completed via asymmetric allylation of (E)-3-iodo-2-methylprop-2-enal
      followed by oxidative cleavage of the terminal vinyl appendage and a Takai
      olefination with pinacol dichloromethylboronate. Esterification of this alcohol
      with a C1-C19 carboxylic acid furnished an open C1-C25 macrolactone precursor,
      but this substance failed to undergo macrocyclization via intramolecular Suzuki
      Miyaura coupling. 

PMID- 25584781
TI  - Opposite Prognostic Significance of Cellular and Serum Circulating MicroRNA-150
      in Patients with Chronic Lymphocytic Leukemia.
AB  - MicroRNAs (or miRs) play a crucial role in chronic lymphocytic leukemia (CLL)
      physiopathology and prognosis. In addition, circulating microRNAs in body fluids
      have been proposed as new biomarkers. We investigated the expression of matched
      cellular and serum circulating microRNA-150 by quantitative real-time PCR (qPCR)
      from purified CD19(+) cells or from CLL serums obtained at diagnosis in a cohort
      of 273/252 CLL patients with a median follow-up of 78 months (range 7-380) and
      correlated it to other biological or clinical parameters. We showed that miR-150
      was significantly overexpressed in CLL cells/serums compared with healthy
      subjects (P < 0.0001). Among CLL patients, a low cellular miR-150 expression
      level was associated with tumor burden, disease aggressiveness and poor
      prognostic factors. In contrast, a high level of serum miR-150 was associated
      with tumor burden markers and some markers of poor prognosis. Similarly, cellular
      and serum miR-150 also predicted treatment-free survival (TFS) and overall
      survival (OS) in an opposite manner: patients with low cellular/serum miR-150
      levels have median TFS of 40/111 months compared with high-level patients who
      have a median TFS of 122/60 months (P < 0.0001/P = 0.0066). Similar results were
      observed for OS. We also found that cellular and serum miR-150 levels vary in an
      opposite manner during disease progression and that cellular miR-150 could be
      regulated by its release into the extracellular space. Cellular and serum levels
      of miR-150 are associated with opposite clinical prognoses and could be used to
      molecularly monitor disease evolution as a new prognostic factor in CLL. 

PMID- 25584784
TI  - Introducing amphiphilicity to noble metal nanoclusters via phase-transfer driven
      ion-pairing reaction.
AB  - Amphiphilicity is a surface property that has yet to be explored for the noble
      metal nanoclusters (NCs). This article shows how amphiphilicity may be added to
      sub-2-nm metal NCs by patching hydrophilic NCs (e.g., Au25(MHA)18 NCs where MHA
      is 6-mercaptohexanoic acid) with hydrophobic cations (e.g.,
      cetyltrimethylammonium ion, CTA(+)) to about half of a monolayer coverage.
      Specifically we demonstrate the preparation of amphiphilic Au25(MHA)18@xCTA NCs
      (x = 6-9 where x is the number of CTA(+) per NC) by the phase-transfer (PT)
      driven ion-paring reaction between CTA(+) and -COO(-) (derived from the
      deprotonation of the terminal carboxyl group of MHA). Due to the coexistence of
      flexible hydrophilic MHA and hydrophobic MHA...CTA ligands in comparable amounts
      on the NC surface, the Au25(MHA)18@xCTA NCs (x = 6-9) exhibit good
      amphiphilicity, which enabled them to dissolve in solvents with distinctly
      different polarities and to self-assemble like a molecular amphiphile.
      Consequently, the amphiphilic Au25(MHA)18@xCTA NCs (x = 6-9) could self-organize
      into stacked bilayers at the air-liquid interface, similar to the formation of
      lyotropic liquid crystalline phases by common surfactants. The good solubility
      and molecular-amphiphile-like self-assembly properties can significantly increase
      the utility of noble metal NCs in basic and applied research. 

PMID- 25584783
TI  - Thiasporines A-C, thiazine and thiazole derivatives from a marine-derived
      Actinomycetospora chlora.
AB  - Thiasporine A (1), the first natural product with a 5-hydroxy-4H-1,3-thiazin-4
      one moiety, along with two new thiazole derivatives, thiasporines B and C (2 and
      3), were isolated from the marine-derived Actinomycetospora chlora SNC-032. The
      structures of 1-3 were established on the basis of comprehensive spectroscopic
      analysis and chemical methods. Thiasporine A showed cytotoxicity against the non
      small-cell lung cancer cell line H2122 with an IC50 value of 5.4 MUM.

PMID- 25584785
TI  - High-level ab initio computations of the absorption spectra of organic iridium
      complexes.
AB  - The excited states of fac-tris(phenylpyridinato)iridium [Ir(ppy)3] and the
      smaller model complex Ir(C3H4N)3 are computed using a number of high-level ab
      initio methods, including the recently implemented algebraic diagrammatic
      construction method to third-order ADC(3). A detailed description of the states
      is provided through advanced analysis methods, which allow a quantification of
      different charge transfer and orbital relaxation effects and give extended
      insight into the many-body wave functions. Compared to the ADC(3) benchmark an
      unexpected striking difference of ADC(2) is found for Ir(C3H4N)3, which derives
      from an overstabilization of charge transfer effects. Time-dependent density
      functional theory (TDDFT) using the B3LYP functional shows an analogous but less
      severe error for charge transfer states, whereas the omegaB97 results are in good
      agreement with ADC(3). Multireference configuration interaction computations,
      which are in reasonable agreement with ADC(3), reveal that static correlation
      does not play a significant role. In the case of the larger Ir(ppy)3 complex,
      results at the TDDFT/B3LYP and TDDFT/omegaB97 levels of theory are presented.
      Strong discrepancies between the two functionals, which are found with respect to
      the energies, characters, as well as the density of the low lying states, are
      discussed in detail and compared to experiment. 

PMID- 25584787
TI  - Delayed presentation of uterine rupture postpartum.

PMID- 25584788
TI  - The right hemisphere contribution to semantic categorization: a TMS study.
AB  - A large amount of evidence suggests an involvement of the right hemisphere in
      lexical-semantic processing, but its specific contribution compared to the left
      hemisphere is not entirely clear. The present study investigated the contribution
      of both hemispheres to the semantic categorization process of words referring to
      typical and atypical exemplars. Transcranial Magnetic Stimulation (TMS) was used
      to interfere with the online activity of Wernicke's area and its right homologue
      during a verbal category membership task. The TMS delayed the responses to
      typical member nouns compared to the control condition, over both areas of
      interest. On the contrary, a delay in the responses to atypical member nouns was
      observed only when the right Wernicke's area was stimulated. Overall, these
      results indicate that while both hemispheres are involved in the categorization
      of typical exemplars, the right hemisphere specifically contributes to semantic
      categorization of atypical ones. 

PMID- 25584789
TI  - A one-pot cascade to protoberberine alkaloids via Stevens rearrangement of
      nitrile-stabilized ammonium ylides.
AB  - A facile one-pot synthesis of protoberberines from readily accessible 1,2,3,4
      tetrahydroisoquinoline-1-carbonitriles and 1,2-bis(bromomethyl)arenes is
      described. The reaction cascade comprises four consecutive transformations, all
      of which can be effected under a single set of conditions. Ten protoberberines,
      including the alkaloids pseudopalmatine and pseudoepiberberine, were prepared in
      yields up to 86% according to this strategy. No chromatographic purification of
      the products is required, and the route is devoid of any protecting group
      manipulations. 

PMID- 25584790
TI  - Determination of the Nucleic Acid Adducts Structure at the  Nucleoside/Nucleotide
      Level by NMR Spectroscopy.
AB  - All living organisms are exposed to xenobiotics from the environment. The
      exposure can lead to the formation of covalent adducts of xenobiotics or their
      metabolites with nucleic acids (NAs).The knowledge of NA adduct structure
      provides valuable information n the mechanism of carcinogenesis on a molecular
      level. While NMR spectroscopy is extremely successful in structural analysis of
      many classes of molecules ranging from small inorganic and organic molecules to
      large biomacromolecules, the structural analysis of NA adducts by NMR
      spectroscopy is accompanied by some challenges. First, the structural diversity
      of the adducts is very large; the electrophilic species generated from the
      metabolism of xenobiotics can attack various atoms of the nucleobases, and new
      rings are frequently formed. The second challenge in the DNA adducts structure
      determination is the low sensitivity of NMR spectroscopy and low amount of the
      adducts isolated from in vivo experiments. Recent developments of NMR hardware
      and experimental methods have led, however, to unprecedented sensitivity. This
      contribution reviews NMR techniques that are commonly applied in the
      determination of nucleic acid adducts structure at the nucleoside/nucleotide
      level. These NMR techniques and the large structural heterogeneity of NA adducts
      are demonstrated on recent examples (mostly published after 2000) of NA adducts
      structure determined by NMR. Most of the examples report 2'-deoxyribonucles(t)ide
      derivatives, but RNA adducts are also briefly discussed. The influence of the
      formation of NA adducts on nucleoside conformation (particularly syn/anti
      orientation of the base) is also demonstrated on recent examples.

PMID- 25584786
TI  - Prion degradation pathways: Potential for therapeutic intervention.
AB  - Prion diseases are fatal neurodegenerative disorders. Pathology is closely linked
      to the misfolding of native cellular PrP(C) into the disease-associated form
      PrP(Sc) that accumulates in the brain as disease progresses. Although treatments
      have yet to be developed, strategies aimed at stimulating the degradation of
      PrP(Sc) have shown efficacy in experimental models of prion disease. Here, we
      describe the cellular pathways that mediate PrP(Sc) degradation and review
      possible targets for therapeutic intervention. This article is part of a Special
      Issue entitled 'Neuronal Protein'. 

PMID- 25584791
TI  - Regulating the timing of CENP-A nucleosome assembly by phosphorylation.
AB  - In this issue of Developmental Cell, Yu et al. (2015) demonstrate that CENP-A
      phosphorylation by CDK1 inhibits its association with the chaperone protein HJURP
      and that the removal of this modification at mitotic exit is a key regulatory
      event that controls the timing of new CENP-A nucleosome formation at centromeres.

PMID- 25584792
TI  - Robo3: the road taken.
AB  - Although axon guidance mechanisms are well conserved across the animal kingdom,
      neuronal circuit complexity increases dramatically in evolution. Reporting
      recently in Neuron, Zelina et al. (2014) uncover mammalian-specific changes in
      Robo3 that result in a switch from repellent to attractive signaling and may have
      contributed to increased mammalian circuit complexity.

PMID- 25584793
TI  - Global resource distribution: allocation of actin building blocks by profilin.
AB  - How cells regulate the distribution of a limited pool of actin between two
      competing structures has long been a mystery. Complementary studies from Suarez
      et al. (2015) and Rotty et al. (2015) now show that profilin controls the
      partitioning of actin monomers between competing actin networks assembled by
      Arp2/3 complex and formins or Ena/VASP.

PMID- 25584794
TI  - Making sense of anti-sense data.
AB  - The morpholino anti-sense technology has been used extensively to test gene
      function. The zebrafish model allows a detailed comparison of knockdown (anti
      sense) and knockout (mutation) effects. Recent studies reveal that these two
      approaches can often lead to surprisingly different phenotypes, thus raising a
      number of important questions. 

PMID- 25584797
TI  - Cdc42 mediates Bmp-induced sprouting angiogenesis through Fmnl3-driven assembly
      of endothelial filopodia in zebrafish.
AB  - During angiogenesis in vivo, endothelial cells (ECs) at the tips of vascular
      sprouts actively extend filopodia that are filled with bundles of linear actin
      filaments. To date, signaling pathways involved in the formation of endothelial
      filopodia have been studied using in-vitro-cultured ECs that behave differently
      from those in vivo. Herein, we have delineated a signaling pathway that governs
      the assembly of endothelial filopodia during angiogenic sprouting of the caudal
      vein plexus (CVP) in zebrafish. During CVP formation, bone morphogenetic protein
      induces the extension of endothelial filopodia and their migration via Arhgef9b
      mediated activation of Cdc42. Active Cdc42 binds to and stimulates Formin-like 3,
      an actin-regulatory protein of the formin family, which, in turn, promotes the
      extension of endothelial filopodia to facilitate angiogenic sprouting of the CVP.
      Thus, this study has elucidated molecular mechanisms underlying the formation of
      endothelial filopodia and their role in angiogenesis in vivo.

PMID- 25584795
TI  - Of flies, mice, and men: evolutionarily conserved tissue damage responses and
      aging.
AB  - Studies in flies, mice, and human models have provided a conceptual framework for
      how paracrine interactions between damaged cells and the surrounding tissue
      control tissue repair. These studies have amassed evidence for an evolutionarily
      conserved secretory program that regulates tissue homeostasis. This program
      coordinates cell survival and proliferation during tissue regeneration and repair
      in young animals. By virtue of chronic engagement, however, it also contributes
      to the age-related decline of tissue homeostasis leading to degeneration,
      metabolic dysfunction, and cancer. Here, we review recent studies that shed light
      on the nature and regulation of this evolutionarily conserved secretory program. 

PMID- 25584798
TI  - Formin-mediated actin polymerization at endothelial junctions is required for
      vessel lumen formation and stabilization.
AB  - During blood vessel formation, endothelial cells (ECs) establish cell-cell
      junctions and rearrange to form multicellular tubes. Here, we show that during
      lumen formation, the actin nucleator and elongation factor, formin-like 3
      (fmnl3), localizes to EC junctions, where filamentous actin (F-actin) cables
      assemble. Fluorescent actin reporters and fluorescence recovery after
      photobleaching experiments in zebrafish embryos identified a pool of dynamic F
      actin with high turnover at EC junctions in vessels. Knockdown of fmnl3
      expression, chemical inhibition of formin function, and expression of dominant
      negative fmnl3 revealed that formin activity maintains a stable F-actin content
      at EC junctions by continual polymerization of F-actin cables. Reduced actin
      polymerization leads to destabilized endothelial junctions and consequently to
      failure in blood vessel lumenization and lumen instability. Our findings
      highlight the importance of formin activity in blood vessel morphogenesis. 

PMID- 25584799
TI  - The effects of aromatherapy on sleep improvement: a systematic literature review
      and meta-analysis.
AB  - OBJECTIVES: To evaluate the existing data on aromatherapy interventions for
      improvement of sleep quality. DESIGN: Systematic literature review and meta
      analysis on the effects of aromatherapy. Study Sources: Electronic databases,
      including the Korea Education and Research Information Service (KERIS), Korean
      studies Information Service System (KISS), National Assembly Library, and eight
      academies within the Korean Society of Nursing Science, were searched to identify
      studies published between 2000 and August 2013. STUDY SELECTION: Randomized
      controlled and quasi-experimental trials that included aromatherapy for the
      improvement of sleep quality. Of the 245 publications identified, 13 studies met
      the inclusion and exclusion criteria, and 12 studies were used in the meta
      analysis. RESULTS: Meta-analysis of the 12 studies using a random-effects model
      revealed that the use of aromatherapy was effective in improving sleep quality
      (95% confidence interval [CI], 0.540-1.745; Z=3.716). Subgroup analysis revealed
      that inhalation aromatherapy (95% CI, 0.792-1.541; Z=6.107) was more effective
      than massage therapy (95% CI, 0.128-2.166; Z=2.205) in unhealthy (95% CI, 0.248
      1.100; Z=3.100) and healthy (95% CI, 0.393-5.104; Z=2.287) participants,
      respectively. CONCLUSION: Readily available aromatherapy treatments appear to be
      effective and promote sleep. Thus, it is essential to develop specific guidelines
      for the efficient use of aromatherapy.

PMID- 25584796
TI  - The endothelial transcription factor ERG promotes vascular stability and growth
      through Wnt/beta-catenin signaling.
AB  - Blood vessel stability is essential for embryonic development; in the adult, many
      diseases are associated with loss of vascular integrity. The ETS transcription
      factor ERG drives expression of VE-cadherin and controls junctional integrity. We
      show that constitutive endothelial deletion of ERG (Erg(cEC-KO)) in mice causes
      embryonic lethality with vascular defects. Inducible endothelial deletion of ERG
      (Erg(iEC-KO)) results in defective physiological and pathological angiogenesis in
      the postnatal retina and tumors, with decreased vascular stability. ERG controls
      the Wnt/beta-catenin pathway by promoting beta-catenin stability, through signals
      mediated by VE-cadherin and the Wnt receptor Frizzled-4. Wnt signaling is
      decreased in ERG-deficient endothelial cells; activation of Wnt signaling with
      lithium chloride, which stabilizes beta-catenin levels, corrects vascular defects
      in Erg(cEC-KO) embryos. Finally, overexpression of ERG in vivo reduces
      permeability and increases stability of VEGF-induced blood vessels. These data
      demonstrate that ERG is an essential regulator of angiogenesis and vascular
      stability through Wnt signaling.

PMID- 25584801
TI  - Multipolar force fields and their effects on solvent dynamics around simple
      solutes.
AB  - The performance of multipole (MTP) and point charge (PC) force fields in
      classical molecular dynamics (MD) simulations of condensed-phase systems for both
      equilibrium and dynamical quantities is compared. MTP electrostatics provides an
      improved description of the anisotropic electrostatic potential, which is
      especially important to describe key, challenging interactions, such as lone
      pairs, pi-interactions, and hydrogen bonds. These chemical environments are
      probed by focusing on the hydration properties of two molecules: N
      methylacetamide and phenyl bromide. Both, equilibrium and dynamical, quantities
      are affected by the quality of the electrostatic model. The alteration of the
      first solvation shell in MTP simulations is validated by comparing with lifetimes
      and correlation times of solute-solvent interactions from experiment. The
      improved dynamical behavior found in the MTP simulations-observed for molecules
      parametrized using very different protocols-suggests that a systematic
      improvement of both equilibrium and dynamical quantities when using MTP
      electrostatics is possible.

PMID- 25584800
TI  - Monochloroacetic acid application is an effective alternative to cryotherapy for
      common and plantar warts in primary care: a randomized controlled trial.
AB  - Cryotherapy and salicylic acid (SA) often fail as treatments for skin warts. We
      examined the effectiveness of monochloroacetic acid (MCA) for patients with
      common or plantar warts. Consecutive patients aged 4 years and older with one or
      more newly diagnosed common or plantar warts were recruited in 53 Dutch general
      practices. We randomly allocated eligible patients to 13-week treatment protocols
      of office-applied MCA versus liquid nitrogen cryotherapy every 2 weeks for
      patients with common warts (n=188), and MCA versus cryotherapy combined with
      daily SA self-application for patients with plantar warts (n=227). The primary
      outcome was the proportion of patients whose warts were all cured at 13 weeks. In
      the common wart group, cure rates were 40/92 (43%, 95% confidence interval 34-54)
      for MCA and 50/93 (54%, 44-64) for cryotherapy (risk difference (RD) -10%, -25
      4.0, P=0.16). In the plantar wart group, cure rates were 49/106 (46%, 37-56) for
      MCA and 45/115 (39%, 31-48) for cryotherapy combined with SA (RD 7.1, 5.9-20,
      P=0.29). For common warts, MCA is an effective alternative to cryotherapy to
      avoid pain during the treatment, although pain after the treatment is similar.
      For plantar warts, office-applied MCA may be preferred over cryotherapy combined
      with SA, on the basis of comparable effectiveness, less treatment pain, and less
      treatment burden. 

PMID- 25584802
TI  - Potent antibacterial nanoparticles for pathogenic bacteria.
AB  - Antibiotic-resistant bacteria have emerged because of the prevalent use of
      antibacterial agents. Thus, new antibacterial agents and therapeutics that can
      treat bacterial infections are necessary. Vancomycin is a potent antibiotic.
      Unfortunately, some bacterial strains have developed their resistance toward
      vancomycin. Nevertheless, it has been demonstrated that vancomycin-immobilized
      nanoparticles (NPs) are capable to be used in inhibition of the cell growth of
      vancomycin-resistant bacterial strains through multivalent interactions. However,
      multistep syntheses are usually necessary to generate vancomycin-immobilized NPs.
      Thus, maintaining the antibiotic activity of vancomycin when the drug is
      immobilized on the surface of NPs is challenging. In this study, a facile
      approach to generate vancomycin immobilized gold (Van-Au) NPs through one-pot
      stirring of vancomycin with aqueous tetrachloroauric acid at pH 12 and 25 
      degrees C for 24 h was demonstrated. Van-Au NPs (8.4 +/- 1.3 nm in size) were
      readily generated. The generated Van-Au NPs maintained their antibiotic
      activities and inhibited the cell growth of pathogens, which included Gram
      positive and Gram-negative bacteria as well as antibiotic-resistant bacterial
      strains. Furthermore, the minimum inhibitory concentration of the Van-Au NPs
      against bacteria was lower than that of free-form vancomycin. Staphylococcus
      aureus-infected macrophages were used as the model samples to examine the
      antibacterial activity of the Van-Au NPs. Macrophages have the tendency to engulf
      Van-Au NPs through endocytosis. The results showed that the cell growth of S.
      aureus in the macrophages was effectively inhibited, suggesting the potential of
      using the generated Van-Au NPs as antibacterial agents for bacterial infectious
      diseases. 

PMID- 25584803
TI  - Glomerular disease in 2014: advances in basic science and translational medicine.
AB  - Knowledge of the pathogenesis of glomerular disease and approaches to therapy
      continued to advance in 2014. Key studies identified thrombospondin type-1 domain
      containing protein 7A as an antigenic target in primary membranous nephropathy,
      and demonstrated efficacy of rituximab as maintenance therapy in relapsing or
      steroid-dependent nephrotic syndrome and antineutrophil cytoplasmic antibody
      associated vasculitis.

PMID- 25584805
TI  - One-step facile solvothermal synthesis of copper ferrite-graphene composite as a
      high-performance supercapacitor material.
AB  - In this work, we reported a facile approach to prepare a uniform copper ferrite
      nanoparticle-attached graphene nanosheet (CuFe2O4-GN). A one-step solvothermal
      method featuring the reduction of graphene oxide and formation of CuFe2O4
      nanoparticles was efficient, scalable, green, and controllable. The composite
      nanosheet was fully characterized by X-ray diffraction (XRD), transmission
      electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), which
      demonstrated that CuFe2O4 nanoparticles with a diameter of approximately 100 nm
      were densely and compactly deposited on GN. To investigate the formation
      mechanism of CuFe2O4-GN, we discussed in detail the effects of a series of
      experimental parameters, including the concentrations of the precursor,
      precipitation agent, stabilizer agent, and graphene oxide on the size and
      morphology of the resulting products. Furthermore, the electrochemical properties
      of the CuFe2O4-GN composite were studied by cyclic voltammetry and galvanostatic
      charge-discharge measurements. The composite showed high electrochemical
      capacitance (576.6 F.g(-1) at 1 A.g(-1)), good rate performance, and cycling
      stability. These results demonstrated that the composite, as a kind of electrode
      materials, had a high specific capacitance and good retention. The versatile
      CuFe2O4-GN holds great promise for application in a wide range of electrochemical
      fields because of the remarkable synergistic effects between CuFe2O4
      nanoparticles and graphene. 

PMID- 25584806
TI  - Plasmonic superlensing in doped GaAs.
AB  - We demonstrate a semiconductor based broadband near-field superlens in the mid
      infrared regime. Here, the Drude response of a highly doped n-GaAs layer induces
      a resonant enhancement of evanescent waves accompanied by a significantly
      improved spatial resolution at radiation wavelengths around lambda = 20 MUm,
      adjustable by changing the doping concentration. In our experiments, gold stripes
      below the GaAs superlens are imaged with a lambda/6 subwavelength resolution by
      an apertureless near-field optical microscope utilizing infrared radiation from a
      free-electron laser. The resonant behavior of the observed superlensing effect is
      in excellent agreement with simulations based on the Drude-Lorentz model. Our
      results demonstrate a rather simple superlens implementation for infrared
      nanospectroscopy. 

PMID- 25584804
TI  - Diverse origins of the myofibroblast-implications for kidney fibrosis.
AB  - Fibrosis is the common end point of chronic kidney disease. The persistent
      production of inflammatory cytokines and growth factors leads to an ongoing
      process of extracellular matrix production that eventually disrupts the normal
      functioning of the organ. During fibrosis, the myofibroblast is commonly regarded
      as the predominant effector cell. Accumulating evidence has demonstrated a
      diverse origin of myofibroblasts in kidney fibrosis. Proposed major contributors
      of myofibroblasts include bone marrow-derived fibroblasts, tubular epithelial
      cells, endothelial cells, pericytes and interstitial fibroblasts; the published
      data, however, have not yet clearly defined the relative contribution of these
      different cellular sources. Myofibroblasts have been reported to originate from
      various sources, irrespective of the nature of the initial damage responsible for
      the induction of kidney fibrosis. Here, we review the possible relevance of the
      diversity of myofibroblast progenitors in kidney fibrosis and the implications
      for the development of novel therapeutic approaches. Specifically, we discuss the
      current status of preclinical and clinical antifibrotic therapy and describe
      targeting strategies that might help support resident and circulating cells to
      maintain or regain their original functional differentiation state. Such
      strategies might help these cells resist their transition to a myofibroblast
      phenotype to prevent, or even reverse, the fibrotic state. 

PMID- 25584809
TI  - Cannabis concerns: increased potency, availability and synthetic analogues.

PMID- 25584807
TI  - Stability of proposed biomarkers of prenatal androgen exposure over the menstrual
      cycle.
AB  - The prenatal hormonal milieu is widely believed to shape health later in life;
      however, there are considerable methodological challenges associated with
      measuring the in utero hormonal environment. Two potential biomarkers of prenatal
      androgen exposure that can be measured postnatally have been proposed: anogenital
      distance (AGD) and the ratio of the second to fourth digits of the hand (2D:4D).
      Although both measures are widely used research tools, their use in adult women
      may be complicated by the dramatic fluctuations in reproductive hormones across
      the menstrual cycle. To determine whether there is cyclical variation in these
      biomarkers, we conducted a longitudinal study of 12 naturally cycling,
      nulliparous adult women. Trained examiners assessed two measures of AGD [anus to
      clitoris (AGD-AC) and anus to fourchette (AGD-AF)] and 2D:4D in both hands for
      the duration of three menstrual cycles, taking measurements during the
      follicular, peri-ovulatory and luteal phases of each cycle. Despite the small
      sample size, longer (more masculine) AGD was associated with lower (more
      masculine) digit ratios, as predicted by the literature. Using multi-level linear
      regression models, we found that AGD and 2D:4D measurements did not differ
      significantly across cycle phases. AGD-AF and digit ratios in both hands were
      associated with age at menarche, suggesting a possible common developmental
      trajectory. These results demonstrate that AGD and 2D:4D are stable across the
      menstrual cycle. In addition, research is needed to determine how reliably these
      measures reflect the in utero hormonal milieu. 

PMID- 25584808
TI  - Identification of miRNAs that modulate glucocerebrosidase activity in Gaucher
      disease cells.
AB  - Gaucher disease is an autosomal recessive disorder caused by deficiency of the
      enzyme glucocerebrosidase. Although it is a monogenic disease, there is vast
      phenotypic heterogeneity, even among patients with the same genotype. MicroRNAs
      (miRNAs) are small non-coding RNAs involved in many biological processes and
      diseases. To determine whether miRNAs can affect glucocerebrosidase activity, we
      performed a screen of 875 different miRNA mimics. The screen was performed using
      Gaucher fibroblasts, and glucocerebrosidase activity was used as the initial
      outcome parameter. We found several miRNAs that either up- or down-regulated
      glucocerebrosidase activity. In follow-up assays, we confirmed that one specific
      miRNA (miR-127-5p) down-regulated both glucocerebrosidase activity and protein
      levels by down-regulation of LIMP-2, the receptor involved in proper trafficking
      of glucocerebrosidase from the endoplasmic reticulum to the lysosome. A
      conditioned media assay demonstrated that cells treated with this miRNA secreted
      glucocerebrosidase into the extracellular environment, supporting impaired LIMP-2
      function. Two other miRNAs, miR-16-5p and miR-195-5p, were found to up-regulate
      glucocerebrosidase activity by greater than 40% and to enhance expression and
      protein levels of the enzyme. In conclusion, we show that miRNAs can alter
      glucocerebrosidase activity in patient cells, indicating that miRNAs can
      potentially act as modifiers in Gaucher disease. 

PMID- 25584810
TI  - Caffeine consumption in children, adolescents and adults.

PMID- 25584811
TI  - Playing the notes of DNA with light: extremely high frequency nanomechanical
      oscillations.
AB  - We use a double nanohole (DNH) optical tweezer with two trapping lasers beating
      to excite the vibrational modes of single-stranded DNA (ssDNA) fragments in the
      extremely high frequency range. We find the resonant vibration frequency of a 20
      base ssDNA to be 40 GHz. We show that the change in the resonant frequency for
      different lengths of the DNA strand is in good agreement with one dimensional
      lattice vibration theory. Thus the DNH tweezer system could distinguish between
      different lengths of DNA strands with resolution down to a few bases. By varying
      the base sequence and length, it is possible to adjust the resonance frequency
      vibration spectrum. The technique shows the potential for use in sequencing
      applications if we can improve the resolution of the present system to detect
      changes in resonant frequency for a single base change in a given sequence. The
      technique is single-molecule and label-free as compared to the existing methods
      used for DNA characterization like gel electrophoresis. 

PMID- 25584812
TI  - Rates of False-Positive Classification Resulting From the Analysis of Additional
      Embedded Performance Validity Measures.
AB  - Several studies have documented improvements in the classification accuracy of
      performance validity tests (PVTs) when they are combined to form aggregated
      models. Fewer studies have evaluated the impact of aggregating additional PVTs
      and changing the classification threshold within these models. A recent Monte
      Carlo simulation demonstrated that to maintain a false-positive rate (FPR) of
      <=.10, only 1, 4, 8, 10, and 15 PVTs should be analyzed at classification
      thresholds of failing at least 1, at least 2, at least 3, at least 4, and at
      least 5 PVTs, respectively. The current study sought to evaluate these findings
      with embedded PVTs in a sample of real-life litigants and to highlight a
      potential danger in analytic flexibility with embedded PVTs. Results demonstrated
      that to maintain an FPR of <=.10, only 3, 7, 10, 14, and 15 PVTs should be
      analyzed at classification thresholds of failing at least 1, at least 2, at least
      3, at least 4, and at least 5 PVTs, respectively. Analyzing more than these
      numbers of PVTs resulted in a dramatic increase in the FPR. In addition, in the
      most extreme case, flexibility in analyzing and reporting embedded PVTs increased
      the FPR by 67%. Given these findings, a more objective approach to analyzing and
      reporting embedded PVTs should be introduced.

PMID- 25584813
TI  - Determining oxidant and antioxidant status in patients with genital warts.
AB  - OBJECTIVES: Warts are abnormal skin growths caused by human papilloma virus (HPV)
      infections within the skin of patients. Genital warts usually appear in the
      perianal and perigenital regions. Asymptomatic warts may be activated after years
      and may damage natural immunity. The inflammation that occurs during this process
      may lead to an imbalance between the prooxidant and the antioxidant systems. The
      aim of this study was to investigate erythrocyte glutathione peroxidase (GSH-Px)
      activity, serum paraoxonase enzyme levels, and oxidative stress levels in
      patients with genital warts. PATIENTS AND METHODS: In total, 32 patients with
      genital warts and 35 healthy subjects were included in this study. Erythrocyte
      GSH-Px activity, serum catalase activity, and paraoxonase enzyme, and
      malondialdehyde (MDA) levels were determined. RESULTS: Erythrocyte GSH-Px
      activity, serum MDA levels, and catalase activity were significantly higher in
      patients with genital warts than in controls (P < 0.01, P < 0.05, and P < 0.05,
      respectively). However, serum paraoxonase enzyme levels were not significantly
      different between groups (P > 0.05). Serum triglyceride levels were significantly
      lower in patients with genital warts than in controls (P < 0.01). However, there
      were no statistically significant differences between groups with respect to
      total cholesterol, high-density lipoprotein cholesterol, or low-density
      lipoprotein cholesterol levels (all P > 0.05). CONCLUSIONS: Our data suggest that
      oxidative stress is increased in genital warts. Increased oxidative stress levels
      may contribute to the pathogenesis of genital warts, and prolonged HPV infection
      due to chronic inflammation could also affect oxidative stress.

PMID- 25584814
TI  - Biodegradable tetra-PEG hydrogels as carriers for a releasable drug delivery
      system.
AB  - We have developed an approach to prepare drug-releasing Tetra-PEG hydrogels with
      exactly four cross-links per monomer. The gels contain two cleavable beta
      eliminative linkers: one for drug attachment that releases the drug at a
      predictable rate, and one with a longer half-life placed in each cross-link to
      control biodegradation. Thus, the system can be optimized to release the drug
      before significant gel degradation occurs. The synthetic approach involves
      placing a heterobifunctional connector at each end of a four-arm PEG prepolymer;
      four unique end-groups of the resultant eight-arm prepolymer are used to tether a
      linker-drug, and the other four are used for polymerization with a second four
      arm PEG. Three different orthogonal reactions that form stable triazoles,
      diazines, or oximes have been used for tethering the drug to the PEG and for
      cross-linking the polymer. Three formats for preparing hydrogel-drug conjugates
      are described that either polymerize preformed PEG-drug conjugates or attach the
      drug postpolymerization. Degradation of drug-containing hydrogels proceeds as
      expected for homogeneous Tetra-PEG gels with minimal degradation occurring in
      early phases and sharp, predictable reverse gelation times. The minimal early
      degradation allows design of gels that show almost complete drug release before
      significant gel-drug fragments are released. 

PMID- 25584815
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration for systematic
      nodal staging of lung cancer in patients with N0 disease by computed tomography
      and integrated positron emission tomography-computed tomography.
AB  - RATIONALE: Data regarding the sensitivity of endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) for staging of lung cancer in
      patients with radiographic N0 disease is scant and inconsistent. With increasing
      use of nonoperative ablative therapies, studies focusing on the performance
      characteristics of EBUS-TBNA in this population are important. OBJECTIVES: To
      evaluate the sensitivity and negative predictive value (NPV) of EBUS-TBNA in
      patients with non-small cell lung cancer and radiographic N0 disease both by
      computed tomography (CT) and positron emission tomography (PET)-CT. METHODS: This
      was a retrospective review of EBUS-TBNA performed for lung cancer staging at two
      major academic centers from 2009 to 2014. Patients with radiographic N0 disease
      (lymph nodes [LN]<=1 cm in the short axis and maximum standardized uptake
      value<=2.5 by PET-CT) were included. Primary outcome was sensitivity and NPV of
      EBUS-TBNA. MEASUREMENTS AND MAIN RESULTS: Two hundred twenty patients with
      radiographic N0 disease underwent EBUS-TBNA, and 734 LN were sampled (median 3,
      range 1-6). Median LN diameter was 0.72 cm. One hundred patients (45.5%)
      underwent surgery, and 120 patients (54.5%) had nonsurgical therapy. N status was
      up-staged in 49 patients (22.3%): 18 by EBUS-TBNA (N1=11, N2=6, N3=1), 27 by
      surgery (N1 intralobar=16, N1 extralobar=3, N2=8 [5 LN in stations 4 and 7, and 3
      LN in stations 5-6), and 4 by imaging follow-up (N1=2, N2=2). Overall false
      negative rate of EBUS was 14.1% (sensitivity, 36.7%; specificity, 100%; and NPV,
      84.7%). False-negative rate was 27 and 3.3% in surgical and nonsurgical
      populations, respectively. Excluding patients with occult disease "outside" the
      reach of EBUS, the overall false-negative rate of EBUS-TBNA was 5.5%
      (sensitivity, 60%; specificity, 100%; and NPV, 93.4%). CONCLUSIONS: This is the
      largest report of EBUS-TBNA in patients with N0 disease by "integrated" PET-CT.
      The majority of false-negative EBUS results were in LN stations outside its
      reach. In our study, both sensitivity and NPV of EBUS-TBNA were lower than early
      reports despite more extensive LN sampling. Given the high false-negative rate of
      imaging modalities, EBUS-TBNA may still play an important role in patients with
      radiographic N0 disease, particularly when nonsurgical ablative therapies are
      planned. Prospective studies are needed to corroborate our findings in the
      nonsurgical population.

PMID- 25584816
TI  - Self-Esteem, Perceived Stress, and Gender During Adolescence: Interactive Links
      to Different Types of Interpersonal Relationships.
AB  - The goal of this study was to analyze the relationships between self-esteem,
      perceived stress, the quality of different types of interpersonal relationships,
      and gender in adolescents. This study used a sample of 1614 adolescent high
      school students and robust data analytic techniques to test the proposed
      relationships. The results partially supported the initial hypothesis in that
      perceived stress mediated the relationships between self-esteem and four of the
      types of interpersonal relationships (i.e., same-sex peer relationships, opposite
      sex peer relationships, parent-child relationships, and teacher-student
      relationships) and moderated the relationship between self-esteem and same-sex
      peer relationships. In addition, a moderated role of gender was also partially
      supported in that perceived stress mediated the relationships between self-esteem
      and same-sex peer relationships, opposite-sex peer relationships, and the parent
      child relationship for girls, but not boys. On the basis of these findings, it
      was concluded that perceived stress plays an intervening role in the relationship
      between self-esteem and different types of interpersonal relationships and that
      gender seems to be a moderator for some of the patterns of the relationships
      between these variables. These findings are discussed in light of the possible
      mechanisms by which the variables could influence each other. Implications for
      theory and practice as well as some directions for future research were also
      suggested. 

PMID- 25584817
TI  - Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules in patients
      taking novel oral anticoagulants.
AB  - BACKGROUND: Ultrasound-guided fine-needle aspiration biopsy (USGFNAB) is the most
      accurate form of evaluation for thyroid nodules. Many patients with thyroid
      nodules who present for USGFNAB are on anticoagulant agents, including the novel
      oral anticoagulants (NOACs), for stroke prevention in atrial fibrillation or
      venous thrombosis prophylaxis. SUMMARY: There has been at least one retrospective
      study describing neck USGFNAB bleeding risks in patients on antithrombotic and/or
      anticoagulant agents. This study concluded that there was no major bleeding risk
      or increase in hematoma formation in patients on antithrombotic or anticoagulant
      agents while undergoing USGFNAB, and there was no need to discontinue these
      agents prior to the procedure. With the emergence of NOACs, further
      recommendations should be made for patients on these agents who will be
      undergoing USGFNAB for thyroid nodules. Currently, there are no published studies
      regarding patients on NOACs who undergo USGFNAB. CONCLUSIONS: It has previously
      been established that patients on historical anticoagulant agents do not need to
      discontinue therapy prior to minor procedures such as needle aspirations or
      dental procedures. Therefore, in patients currently taking dabigatran,
      rivaroxaban, or apixaban, it is concluded that it is reasonable and safe to
      continue the novel oral anticoagulant agents prior to USGFNAB of thyroid nodules
      without major risk of bleeding. This conclusion is based not only on the fact
      that minor procedures are considered safe in patients on NOACs, but also because
      patients on historical anticoagulant agents do not need to discontinue therapy
      prior to minor procedures.

PMID- 25584818
TI  - Sense-antisense (complementary) peptide interactions and the proteomic code;
      potential opportunities in biology and pharmaceutical science.
AB  - INTRODUCTION: A sense peptide can be defined as a peptide whose sequence is coded
      by the nucleotide sequence (read 5' -> 3') of the sense (positive) strand of DNA.
      Conversely, an antisense (complementary) peptide is coded by the corresponding
      nucleotide sequence (read 5' -> 3') of the antisense (negative) strand of DNA.
      Research has been accumulating steadily to suggest that sense peptides are
      capable of specific interactions with their corresponding antisense peptides.
      Unfortunately, although more and more examples of specific sense-antisense
      peptide interactions are emerging, the very idea of such interactions does not
      conform to standard biology dogma and so there remains a sizeable challenge to
      lift this concept from being perceived as a peripheral phenomenon if not worse,
      into becoming part of the scientific mainstream. AREAS COVERED: Specific
      interactions have now been exploited for the inhibition of number of widely
      different protein-protein and protein-receptor interactions in vitro and in vivo.
      Further, antisense peptides have also been used to induce the production of
      antibodies targeted to specific receptors or else the production of anti
      idiotypic antibodies targeted against auto-antibodies. Such illustrations of
      utility would seem to suggest that observed sense-antisense peptide interactions
      are not just the consequence of a sequence of coincidental 'lucky-hits'. Indeed,
      at the very least, one might conclude that sense-antisense peptide interactions
      represent a potentially new and different source of leads for drug discovery. But
      could there be more to come from studies in this area? EXPERT OPINION: Studies on
      the potential mechanism of sense-antisense peptide interactions suggest that
      interactions may be driven by amino acid residue interactions specified from the
      genetic code. If so, such specified amino acid residue interactions could form
      the basis for an even wider amino acid residue interaction code (proteomic code)
      that links gene sequences to actual protein structure and function, even entire
      genomes to entire proteomes. The possibility that such a proteomic code should
      exist is discussed. So too the potential implications for biology and
      pharmaceutical science are also discussed were such a code to exist.

PMID- 25584820
TI  - Decision making in cancer-related topic avoidance.
AB  - In this article, the authors use the Disclose Decision-Making Model to explore
      cancer-related topic avoidance among cancer patients and their partners.
      Participants include 95 dyads in which 1 partner had been diagnosed and/or
      treated for cancer. Variables of interest include death-, future-, sexuality-,
      and burden-related topic avoidance and dimensions of the Disclosure Decision
      Making Model including information assessment, receiver assessment, relational
      quality, and discloser efficacy. Data were analyzed using linear regressions.
      Findings suggest that lack of reciprocity and efficacy are predictors of topic
      avoidance. The authors discuss implications of findings and suggests direction
      for future research. 

PMID- 25584821
TI  - Immune surveillance by rhinovirus-specific circulating CD4+ and CD8+ T
      lymphocytes.
AB  - BACKGROUND: It is difficult to experimentally infect volunteers with RV strains
      to which the subject demonstrates serological immunity. However, in RV
      challenges, viral clearance begins before de novo adaptive immune responses would
      develop. We speculated that adaptive immunity to RV reflects heterologous
      immunity by effector memory cells. METHODS: DCs were generated from monocytes
      using GM-CSF and IL-4 and RV39 loading accomplished with a dose of ~ 350
      TCID50/10(5) cells. RV-induced maturation was established as modulation of MHC
      class II, CD80, CD83, and CD86. Circulating RV targeting CD4 and CD8 T cells were
      investigated as induction of RV-specific proliferation (CFSE-dilution). RESULTS:
      Maturation of DC by RV was confirmed as upregulation of MHC Class II (83.3 +/-
      5.0% to 87.8 +/- 4.1%), CD80 (39.4 +/- 7.2% to 47.6 +/- 7.7%) and CD86 (78.4 +/-
      4.7% to 84.1 +/- 3.4%). Both CD4 and CD8 memory T cells were recognized in the
      circulation of healthy subjects. CONCLUSIONS: RV drives DC maturation and results
      in their ability to present RV antigens to both T helper and cytotoxic
      lymphocytes. Both CD4 and CD8 cells capable of recognizing RV-associated antigens
      are present in the circulation of healthy subjects where they are presumably
      involved in immune surveillance and explain the rapid recruitment of an adaptive
      immune response during RV infection.

PMID- 25584823
TI  - New methods for assessing response in acute myeloid leukemia.
AB  - PURPOSE OF REVIEW: Patients with acute myeloid leukemia typically are monitored
      with bone marrow biopsy 7-10 days after completion of induction therapy. However,
      this test has relatively poor sensitivity and specificity for classifying
      patients likely to have long-term cure or even patients who will need additional
      therapy to achieve complete remission. Several new methods of assessing response
      are being studied and are summarized in this review. RECENT FINDINGS: Many new
      methods are being used to evaluate response assessment. Emerging data suggest
      that various types of clinical, chemical, and imaging biomarkers, as well as more
      sensitive techniques to measure minimal residual disease, can all help provide
      more accurate response assessment and prognostic information. SUMMARY: New
      techniques will improve the way we assess response to acute myeloid leukemia
      therapy. Larger confirmatory studies utilizing these novel markers of response to
      change treatment and to improve clinical outcomes are urgently needed.

PMID- 25584826
TI  - Controversies in pancreas transplantation.
AB  - Pancreas transplants are now highly effective for patients with diabetes
      mellitus. Improvements in outcomes have primarily been due to significant
      reductions in technical failures and immunological graft loss. In this short
      review we discuss three areas of controversy in the field of pancreas
      transplantation. Notwithstanding the controversies we have highlighted, in line
      with the American Diabetic Association position statement, simultaneous pancreas
      kidney transplants and pancreas after kidney transplants should be routine for
      diabetic kidney recipients, and a pancreas transplant alone is appropriate for
      non-uremic labile diabetic patients. 

PMID- 25584822
TI  - Urinary amino acid alterations in 3-year-old children with neurodevelopmental
      effects due to perinatal dioxin exposure in Vietnam: a nested case-control study
      for neurobiomarker discovery.
AB  - In our previous study of 3-year-old children in a dioxin contamination hot spot
      in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group
      during the perinatal period displayed lower Bayley III neurodevelopmental scores,
      whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group
      displayed increased autistic traits. In autistic children, urinary amino acid
      profiles have revealed metabolic alterations in the amino acids that serve as
      neurotransmitters in the developing brain. Therefore, our present study aimed to
      investigate the use of alterations in urinary amino acid excretion as biomarkers
      of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year
      old children in Vietnam. A nested case-control study of urinary analyses was
      performed for 26 children who were selected from 111 3-year-old children whose
      perinatal dioxin exposure levels and neurodevelopmental status were examined in
      follow-up surveys conducted in a dioxin contaminated hot spot. We compared
      urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs
      and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group;
      (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ
      PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and
      tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD
      group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the
      low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to
      glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD
      group. Furthermore, urinary histidine levels and the ratio of histidine to
      glycine were significantly correlated with neurodevelopmental scores,
      particularly for language and fine motor skills. These results indicate that
      urinary histidine is specifically associated with dioxin exposure-induced
      neurodevelopmental deficits, suggesting that urinary histidine may be a useful
      marker of dioxin-induced neurodevelopmental deficits and that histaminergic
      neurotransmission may be an important pathological contributor to dioxin-mediated
      neurotoxicity. 

PMID- 25584827
TI  - The physiologist Ewald Hering (1834-1918): curriculum vitae.

PMID- 25584828
TI  - The prevalence of strabismus in 7-year-old schoolchildren in Iran.
AB  - PURPOSE: To determine the prevalence of tropia and phoria in Iran and their
      association with some related factors. METHODS: In a cross-sectional population
      based study, multistage randomized cluster sampling was used to select
      participants from among grade 1 students in the primary schools of 7 cities of
      Iran. After obtaining their parents' approval, the students underwent the
      measurement of uncorrected and corrected visual acuity, cycloplegic refraction,
      and cover test. Distant and near cover test were performed at 6 m and 40 cm,
      respectively, with the best corrected visual acuity. Tropia and phoria were
      measured separately. RESULTS: Of 4157 selected students, 3675 participated in the
      study. The prevalence of strabismus was 1.68% (95% CI 1.13-2.23). The prevalence
      of strabismus was 2.17% (95% CI 1.06-3.29) in boys and 1.27% (95% CI 0.57-1.96)
      in girls (p = 0.216). Moreover, 1.27% (95% CI 0.82-1.72) of the children had
      exotropia and 0.44% (95% CI 0.22-0.65) had esotropia. The prevalence of constant
      and intermittent strabismus was 0.73% (95% CI 0.26-1.19) and 0.96% (95% CI 0.55
      1.36), respectively. Phoria was detected in 32.98% (95% CI 24.25-41.71) of the
      children in this study. The prevalence of residual amblyopia was 23.77% (95% CI
      9.45-38.08) in strabismic and 1.43% (95% CI 0.09-1.96) in non-strabismic children
      (p < 0.001). The odds of strabismus were significantly higher in hyperopic and
      astigmatic children. CONCLUSION: This study showed the prevalence of tropia and
      phoria across Iran. Exotropia was the most common type of tropia in Iran and
      intermittent strabismus was the most common type of strabismus. Due to prevalent
      amblyopia in strabismus, attention should be directed toward careful screening
      and treatment.

PMID- 25584829
TI  - Cell cycle control (and more) by programmed -1 ribosomal frameshifting:
      implications for disease and therapeutics.
AB  - Abstract Like most basic molecular mechanisms, programmed -1 ribosomal
      frameshifting (-1 PRF) was first identified in viruses. Early observations that
      global dysregulation of -1 PRF had deleterious effects on yeast cell growth
      suggested that -1 PRF may be used to control cellular gene expression, and the
      cell cycle in particular. Collection of sufficient numbers of viral -1 PRF
      signals coupled with advances in computer sciences enabled 2 complementary
      computational approaches to identify -1 PRF signals in free living organisms. The
      unexpected observation that almost all -1 PRF events on eukaryotic mRNAs direct
      ribosomes to premature termination codons engendered the hypothesis that -1 PRF
      signals post-transcriptionally regulate gene expression by functioning as mRNA
      destabilizing elements. Emerging research suggests that some human diseases are
      associated with global defects in -1 PRF. The recent discovery of -1 PRF signal
      specific trans-acting regulators may provide insight into novel therapeutic
      strategies aimed at treating diseases caused by changes in gene expression
      patterns. 

PMID- 25584830
TI  - Isolation and biochemical characterization of Apios tuber lectin.
AB  - Apios tuber lectin, named ATL, was isolated from Apios americana Medikus by two
      chromatography steps, hydrophobic chromatography and anion-exchange
      chromatography. The minimum concentration required for the hemagglutination
      activity toward rabbit erythrocytes of ATL was 4 MUg/mL. ATL was composed of a
      homodimer of 28.4 kDa subunits. The amino acid sequence of ATL was similar to
      those of other legume lectins. The lectin showed moderate stability toward
      heating and acidic pH, and the binding affinity against several monosaccharides,
      such as D-glucosamine and D-galactosamine. ATL also bound to desialylated or
      agalactosylated glycoproteins such as asialo and agalacto transferrin. ATL
      decreased the transepithelial electrical resistance across human intestinal Caco
      2 cell monolayers, suggesting the effect on the tight junction-mediated
      paracellular transport. 

PMID- 25584831
TI  - Neuroprotective and neuroregenerative effects of nimodipine in a model system of
      neuronal differentiation and neurite outgrowth.
AB  - Nimodipine is a Ca2+-channel antagonist mainly used for the management of
      aneurysmal subarachnoid hemorrhage (aSAH) to prevent cerebral vasospasms.
      However, it is not clear if the better outcome of nimodipine-treated patients is
      mainly due to vasodilatation or whether other cellular neuroprotective or
      neuregenerative effects of nimodipine are involved. We analysed PC12 cells after
      different stress stimuli with or without nimodipine pretreatment. Cytotoxicity of
      200 mM EtOH and osmotic stress (450 mosmol/L) was significantly reduced with
      nimodipine pretreatment, while nimodipine has no influence on the hypoxia-induced
      cytotoxicity in PC12 cells. The presence of nimodipine also increased the NGF
      induced neurite outgrowth in PC12 cells. However, nimodipine alone was not able
      to induce neurite outgrowth in PC12 cells. These results support the idea that
      nimodipine has general neuroprotective or neuregenerative effect beside its role
      in vasodilatation and is maybe useful also in other clinical applications beside
      aSAH. 

PMID- 25584832
TI  - Combined pharmacophore modeling, 3D-QSAR, homology modeling and docking studies
      on CYP11B1 inhibitors.
AB  - The mitochondrial cytochrome P450 enzymes inhibitor steroid 11beta-hydroxylase
      (CYP11B1) can decrease the production of cortisol. Therefore, these inhibitors
      have an effect in the treatment of Cushing's syndrome. A pharmacophore model
      generated by Genetic Algorithm with Linear Assignment for Hypermolecular
      Alignment of Datasets (GALAHAD) was used to align the compounds and perform
      comparative molecular field analysis (CoMFA) with Q2 = 0.658, R2 = 0.959. The
      pharmacophore model contained six hydrophobic regions and one acceptor atom, and
      electropositive and bulky substituents would be tolerated at the A and B sites,
      respectively. A three-dimensional quantitative structure-activity relationship
      (3D-QSAR) study based on the alignment with the atom root mean square (RMS) was
      applied using comparative molecular field analysis (CoMFA) with Q2 = 0.666, R2 =
      0.978, and comparative molecular similarity indices analysis (CoMSIA) with Q2 =
      0.721, R2 = 0.972. These results proved that all the models have good
      predictability of the bioactivities of inhibitors. Furthermore, the QSAR models
      indicated that a hydrogen bond acceptor substituent would be disfavored at the A
      and B groups, while hydrophobic groups would be favored at the B site. The three
      dimensional (3D) model of the CYP11B1 was generated based on the crystal
      structure of the CYP11B2 (PDB code 4DVQ). In order to probe the ligand-binding
      modes, Surflex-dock was employed to dock CYP11B1 inhibitory compounds into the
      active site of the receptor. The docking result showed that the imidazolidine
      ring of CYP11B1 inhibitors form H bonds with the amino group of residue Arg155
      and Arg519, which suggested that an electronegative substituent at these
      positions could enhance the activities of compounds. All the models generated by
      GALAHAD QSAR and Docking methods provide guidance about how to design novel and
      potential drugs for Cushing's syndrome treatment. 

PMID- 25584833
TI  - Synthesis and in vitro screening of phenylbipyridinylpyrazole derivatives as
      potential antiproliferative agents.
AB  - A series of phenylbipyridinylpyrazoles was synthesized through the reaction of 2
      (4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1
      yl)acetonitrile (4) with different 6-substituted pyridine-3-ylboronic acids. The
      final compounds 5a-j were screened at 10 uM against over 60 tumor cell lines at
      the U.S. National Cancer Institute (NCI). In light of the NCI results, compounds
      5c and 5h showed a broad spectrum of activity against NCI cell lines with mean
      growth of 53% and 58%, respectively. Compound 5e behaved differently as it showed
      high degree of selectivity and potency by inhibiting 96% of growth of leukemia SR
      cell line at 10 uM. Standard COMPARE analyses were performed at the GI50 level
      and the results exhibit high correlation in the form of pairwise correlation
      coefficient (PCC) of more than 0.6 between three of the current compounds and
      three standard known anticancer agents. Compound 5e demonstrated high correlation
      levels with merbarone (NSC S336628) with a PCC value of 0.631. Compound 5h showed
      a considerably high PCC value of 0.626 with dichloroallyl lawsone, while compound
      5i, showed PCC values of 0.601 and 0.604 with both dichloroallyl lawsone and N,N
      dibenzyldaunomycin (NSC S268242), respectively. These three standard agents have
      anticancer activity via two major mechanism of actions, inhibition of
      topoisomerase II and inhibition of biosynthesis of pyrimidine nucleotides,
      therefore, compounds 5a-j are promising therapeutic agents for targeting
      different human malignancies. Prediction of drug-likeness and toxicity of these
      newly synthesized derivatives were also considered. 

PMID- 25584834
TI  - TiO2 and Fe2O3 films for photoelectrochemical water splitting.
AB  - Titanium oxide (TiO2) and iron oxide (alpha-Fe2O3) hematite films have potential
      applications as photoanodes in electrochemical water splitting. In the present
      work TiO2 and alpha-Fe2O3 thin films were prepared by two methods, e.g., sol-gel
      and High Power Impulse Magnetron Sputtering (HiPIMS) and judged on the basis of
      physical properties such as crystalline structure and surface topography and
      functional properties such as simulated photoelectrochemical (PEC) water
      splitting conditions. It was revealed that the HiPIMS method already provides
      crystalline structures of anatase TiO2 and hematite Fe2O3 during the deposition,
      whereas to finalize the sol-gel route the as-deposited films must always be
      annealed to obtain the crystalline phase. Regarding the PEC activity, both TiO2
      films show similar photocurrent density, but only when illuminated by UV light. A
      different situation was observed for hematite films where plasmatic films showed
      a tenfold enhancement of the stable photocurrent density over the sol-gel
      hematite films for both UV and visible irradiation. The superior properties of
      plasmatic film could be explained by ability to address some of the hematite
      drawbacks by deposition of very thin films (25 nm) consisting of small densely
      packed particles and by doping with Sn. 

PMID- 25584835
TI  - An improved HPLC-DAD method for quantitative comparisons of triterpenes in
      Ganoderma lucidum and its five related species originating from Vietnam.
AB  - An HPLC-DAD method for the quality control of wild and cultivated Ganoderma
      lucidum (Linhzhi) and related species samples was developed and validated. The
      quantitative determination of G. lucidum and its related species using 14
      triterpene constituents, including nine ganoderma acids (compounds 4-12), four
      alcohols (compounds 13-16), and one sterol (ergosterol, 17) were reported. The
      standard curves were linear over the concentration range of 7.5-180 ug/mL. The
      LOD and LOQ values for the analyses varied from 0.34 to 1.41 ug/mL and from 1.01
      to 4.23 ug/mL, respectively. The percentage recovery of each reference compound
      was found to be from 97.09% to 100.79%, and the RSD (%) was less than 2.35%. The
      precision and accuracy ranged from 0.81%-3.20% and 95.38%-102.19% for intra-day,
      and from 0.43%-3.67% and 96.63%-103.09% for inter-day, respectively. The study
      disclosed in detail significant differences between the quantities of analyzed
      compounds in different samples. The total triterpenes in wild Linhzhi samples
      were significantly higher than in cultivated ones. The total constituent contents
      of the five related Linhzhi samples were considerably lower than that in the G.
      lucidum specimens, except for G. australe as its constituent content outweighed
      wild Linhzhi's content by 4:1. 

PMID- 25584836
TI  - Development of new 1,3-diazaphenoxazine derivatives (thioG-grasp) to covalently
      capture 8-thioguanosine.
AB  - The derivatives of 8-thioguanosine are thought to be included in the signal
      transduction system related to 8-nitroguanosine. In this study, we attempted to
      develop new 1,3-diazaphenoxazine (G-clamp) derivatives to covalently capture 8
      thioguanosine (thioG-grasp). It was expected that the chlorine atom at the end of
      the linker would be displaced by the nucleophilic attack by the sulfur atom of 8
      thioguanosine via multiple hydrogen-bonded complexes. The thioG-grasp derivative
      with a propyl linker reacted efficiently with 8-thioguanosine to form the
      corresponding adduct. 

PMID- 25584837
TI  - Psychotropic medication use in French children and adolescents.
AB  - OBJECTIVE: The purpose of this study was to describe the patterns of psychotropic
      drug use in a large representative population of children and adolescents drawn
      from the French National Health Insurance databank. METHODS: Data were drawn from
      a sample of 1% of the beneficiaries of the French national health insurance,
      selecting those 0-17 years old in 2010 (n=128,298). In addition to age and
      gender, data included the identification number of each drug allowing a European
      Pharmaceutical Marketing Research Association (EphMRA) classification, as well as
      the type of the prescriber. RESULTS: Overall, 2.5% of children and adolescents
      had been prescribed psychotropic medication. A majority were prescribed
      anxiolytics (1.9%), followed by antidepressants (0.3%), antipsychotics (0.3%),
      and stimulants (0.2%). Between the ages of 15 and 17, 6.1% of girls were
      prescribed anxiolytics and 1.1% were prescribed antidepressants. For boys, the
      anxiolytics remained the most prescribed psychotropic medication; however,
      between the ages of 11 and 14, and between the ages of 15 and 17 they received
      more antipsychotics (0.7% and 0.8%) and between the ages of 6 and 10, and between
      the ages of 11 and 14 (0.7% and 0.6%), they were prescribed more stimulants than
      were girls. Among those who received a prescription, a majority of youth (84.6%)
      received only one class of drugs, and general practitioners were found to be
      prescribing most of these prescriptions (81.7%). CONCLUSIONS: The prevalence of
      psychotropic drug use in France is similar to that of the Netherlands and much
      lower than what is observed in the United States. Stimulants are less frequently
      prescribed in France than in other European countries, but anxiolytics are
      prescribed considerably more in France than in any other country.

PMID- 25584838
TI  - Bipyridine hydrogel for selective and visible detection and absorption of Cd(2+).
AB  - Herein, we report for the first time the use of bipyridine-based hydrogel for
      selective and visible detection and absorption of Cd(2+). At low concentrations,
      hydrogelator 1 was applied for selective detection of Cd(2+) in vitro and in
      living cells with high sensitivity. In the absence of metal ions, 1 is
      nonfluorescent at 470 nm. Upon addition of metal ions, 1 selectively coordinates
      to Cd(2+), causing an 86-fold increase of fluorescence intensity at 470 nm via
      the chelation enhanced fluorescence (CHEF) effect, as revealed by first
      principles simulations. At 1.5 wt% and pH 5.5, 1 self-assembles into nanofibers
      to form hydrogel Gel I. Since Cd(2+) could actively participate in the
      hydrogelation and promote the self-assembly, we also successfully applied Gel I
      for visible detection and absorption of Cd(2+). With these excellent properties,
      Gel I is expected to be explored as one type of versatile biomaterial for not
      only environmental monitoring but also for pollution treatment in the near
      future.

PMID- 25584854
TI  - Resonant-convergent PCM response theory for the calculation of second harmonic
      generation in makaluvamines A-V: pyrroloiminoquinone marine natural products from
      poriferans of genus Zyzzya.
AB  - The first-order hyperpolarizability, beta, has been calculated for a group of
      marine natural products, the makaluvamines. These compounds possess a common
      cationic pyrroloiminoquinone structure that is substituted to varying degrees.
      Calculations at the MP2 level indicate that makaluvamines possessing phenolic
      side chains conjugated with the pyrroloiminoquinone moiety display large beta
      values, while breaking this conjugation leads to a dramatic decrease in the
      calculated hyperpolarizability. This is consistent with a charge-transfer donor
      pi-acceptor (D-pi-A) structure type, characteristic of nonlinear optical
      chromophores. Dynamic hyperpolarizabilities calculated using resonance-convergent
      time-dependent density functional theory coupled to polarizable continuum model
      (PCM) solvation suggest that significant resonance enhancement effects can be
      expected for incident radiation with wavelengths around 800 nm. The results of
      the current work suggest that the pyrroloiminoquinone moiety represents a
      potentially useful new chromophore subunit, in particular for the development of
      molecular probes for biological imaging. The introduction of solvent-solute
      interactions in the theory is conventionally made in a density matrix formalism,
      and the present work will provide detailed account of the approximations that
      need to be introduced in wave function theory and our program implementation. The
      program implementation as such is achieved by a mere combination of existing
      modules from previous developments, and it is here only briefly reviewed. 

PMID- 25584855
TI  - Differential effects of dopamine receptor subtype-specific agonists with respect
      to operant behavior maintained on a differential reinforcement of low-rate
      responding (DRL) schedule.
AB  - Previous studies have shown that d-amphetamine, a dopamine (DA) indirect agonist,
      alters operant responding with respect to the behavior maintained on a
      differential reinforcement of low-rate (DRL) schedule of reinforcement. These
      behavioral changes have been presumed to result from drug-induced
      hyperdopaminergia that leads to activation of DA receptors. This study
      investigated the acute dose effects of DA receptor subtype-selective agonists on
      the performance of DRL 10-sec behavior by rats. SKF38393 (a D1 receptor agonist)
      and quinpirole (a D2/D3 receptor agonist) were able to dose-dependently disrupt
      DRL 10-sec behavior by decreasing the total responses, the non-reinforced
      responses, and the peak rate of response. Bromocriptine (a D2/D3 receptor
      agonist) produced a significantly different pattern of behavioral changes when
      examined during two distinct time phases (15 min and 3 hr after the drug
      injection). DRL responding was only altered at higher doses of bromocriptine in
      the second phase as indicated by decreasing reinforced responses and peak rate,
      together with an increase of burst responses. In contrast to the D1 and D2/D3
      receptor agonists, PD168077 (a D4 receptor agonist) did not affect DRL 10-sec
      behavior. None of these tested drugs affected DRL 10-sec behavior in a manner
      similar to that of d-amphetamine. These findings show that there are differential
      effects on the performance of DRL 10-sec behavior when drugs are able to
      preferentially activate D1, D2/D3 and D4 receptors, supporting the assertion that
      there is functional heterogeneity of the DA receptor subtypes.

PMID- 25584857
TI  - Flexible and stackable laser-induced graphene supercapacitors.
AB  - In this paper, we demonstrate that by simple laser induction, commercial
      polyimide films can be readily transformed into porous graphene for the
      fabrication of flexible, solid-state supercapacitors. Two different solid-state
      electrolyte supercapacitors are described, namely vertically stacked graphene
      supercapacitors and in-plane graphene microsupercapacitors, each with enhanced
      electrochemical performance, cyclability, and flexibility. Devices with a solid
      state polymeric electrolyte exhibit areal capacitance of >9 mF/cm2 at a current
      density of 0.02 mA/cm2, more than twice that of conventional aqueous
      electrolytes. Moreover, laser induction on both sides of polyimide sheets enables
      the fabrication of vertically stacked supercapacitors to multiply its
      electrochemical performance while preserving device flexibility.

PMID- 25584858
TI  - Nanoporous delafossite CuAlO2 from inorganic/polymer double gels: a desirable
      high-surface-area p-type transparent electrode material.
AB  - Nanoporous structures of a p-type semiconductor, delafossite CuAlO(2), with a
      high crystallinity have been fabricated through an inorganic/polymer double-gel
      process and characterized for the first time via Mott-Schottky measurements. The
      effect of the precursor concentration, calcination temperature, and atmosphere
      were examined to achieve high crystallinity and photoelectrochemical properties
      while maximizing the porosity. The optical properties of the nanoporous CuAlO(2)
      are in good agreement with the literature with an optical band gap of 3.9 eV, and
      the observed high electrical conductivity and hole concentrations conform to
      highly crystalline and well-sintered nanoparticles observed in the product. The
      Mott-Schottky plot from the electrochemical impedance spectroscopy studies
      indicates a flat-band potential of 0.49 V versus Ag/AgCl. It is concluded that
      CuAlO(2) exhibits band energies very close to those of NiO but with electrical
      properties very desirable in the fabrication of photoelectrochemical devices
      including dye-sensitized solar cells.

PMID- 25584856
TI  - The role of active site tyrosine 58 in Citrobacter freundii methionine gamma
      lyase.
AB  - In the spatial structure of methionine gamma-lyase (MGL, EC 4.4.1.11) from
      Citrobacter freundii, Tyr58 is located at H-bonding distance to the oxygen atom
      of the phosphate "handle" of pyridoxal 5'-phosphate (PLP). It was replaced for
      phenylalanine by site-directed mutagenesis. The X-ray structure of the mutant
      enzyme was determined at 1.96A resolution. Comparison of spatial structures and
      absorption spectra of wild-type and mutant holoenzymes demonstrated that the
      replacement did not result in essential changes of the conformation of the active
      site Tyr58Phe MGL. The Kd value of PLP for Tyr58Phe MGL proved to be comparable
      to the Kd value for the wild-type enzyme. The replacement led to a decrease of
      catalytic efficiencies in both gamma- and beta-elimination reactions of about two
      orders of magnitude as compared to those for the wild-type enzyme. The rates of
      exchange of C-alpha- and C-beta- protons of inhibitors in D2O catalyzed by the
      mutant form are comparable with those for the wild-type enzyme. Spectral data on
      the complexes of the mutant form with the substrates and inhibitors showed that
      the replacement led to a change of rate the limiting step of the physiological
      reaction. The results allowed us to conclude that Tyr58 is involved in an optimal
      positioning of the active site Lys210 at some stages of gamma- and beta
      elimination reactions. This article is part of a Special Issue entitled: Cofactor
      dependent proteins: evolution, chemical diversity and bio-applications. 

PMID- 25584859
TI  - Synthesis and transport properties of large-scale alloy Co(0.16)Mo(0.84)S2
      bilayer nanosheets.
AB  - Synthesis of large-scale highly crystalline two-dimensional alloys is significant
      for revealing properties. Here, we have investigated the vapor growth process of
      high-quality bilayer CoxMo1-xS2 (x = 0.16) hexagonal nanosheets systematically.
      As the initial loading of the sulfur increases, the morphology of the CoxMo1-xS2
      (0 < x <= 1) nanosheets becomes hexagons from David stars step by step at 680 
      degrees C. We find that Co atoms mainly distribute at the edge of nanosheets.
      When the temperature increases from 680 to 750  degrees C, high-quality cubic
      pyrite-type crystal structure CoS2 grows on the surface of CoxMo1-xS2 nanosheet
      gradually and forms hexagonal film induced by the nanosheet. Electrical transport
      measurements reveal that the CoxMo1-xS2 nanosheets and CoS2 films exhibit n-type
      semiconducting transport behavior and half-metallic behavior, respectively.
      Theoretical calculations of their band structures agree well with the
      experimental results. 

PMID- 25584860
TI  - Doxorubicin-loaded glycyrrhetinic acid modified recombinant human serum albumin
      nanoparticles for targeting liver tumor chemotherapy.
AB  - Due to overexpression of glycyrrhetinic acid (GA) receptor in liver cancer cells,
      glycyrrhetinic acid modified recombinant human serum albumin (rHSA) nanoparticles
      for targeting liver tumor cells may result in increased therapeutic efficacy and
      decreased adverse effects of cancer therapy. In this study, doxorubicin (DOX)
      loaded and glycyrrhetinic acid modified recombinant human serum albumin
      nanoparticles (DOX/GA-rHSA NPs) were prepared for targeting therapy for liver
      cancer. GA was covalently coupled to recombinant human serum albumin
      nanoparticles, which could efficiently deliver DOX into liver cancer cells. The
      resultant GA-rHSA NPs exhibited uniform spherical shape and high stability in
      plasma with fixed negative charge (~-25 mV) and a size about 170 nm. DOX was
      loaded into GA-rHSA NPs with a maximal encapsulation efficiency of 75.8%.
      Moreover, the targeted NPs (DOX/GA-rHSA NPs) showed increased cytotoxic activity
      in liver tumor cells compared to the nontargeted NPs (DOX/rHSA NPs, DOX loaded
      recombinant human serum albumin nanoparticles without GA conjugating). The
      targeted NPs exhibited higher cellular uptake in a GA receptor-positive liver
      cancer cell line than nontargeted NPs as measured by both flow cytometry and
      confocal laser scanning microscopy. Biodistribution experiments showed that
      DOX/GA-rHSA NPs exhibited a much higher level of tumor accumulation than
      nontargeted NPs at 1 h after injection in hepatoma-bearing Balb/c mice.
      Therefore, the DOX/GA-rHSA NPs could be considered as an efficient nanoplatform
      for targeting drug delivery system for liver cancer. 

PMID- 25584863
TI  - [Psychometric evaluation of the Dissociative Experiences Scale-Taxon (DES-T)].
AB  - Current refinements of the dissociation concept have arrived at the distinction
      between a dimensional, non-pathological type and a discontinuous, pathological
      class of dissociation, which can be identified by a subset of 8 items of the
      Dissociative Experiences Scale, the DES-Taxon (DES-T). This study reports on the
      psychometric evaluation of the German version of the DES-T in a large general
      population sample (n = 2,359). The distributions of all items and the total score
      of the DES-T emerged to be non-normal and right-skewed with a sharp peak. The
      internal consistency proved to be high (Cronbach's alpha = 0.92), and all items
      discriminated well with item-total correlations above 0.65. An explorative factor
      analysis revealed that all items loaded on the first, unrotated factor with
      loadings of a >= 0.7 (explained variance 64%). The DES-T is a one-dimensional
      measure as indicated by confirmatory factor analysis. There were no relevant
      associations between the DES-T, sociodemographic characteristics, depression or
      anxiety. The prevalence of pathological dissociation was 1.6% in the general
      population. The DES-T proved to be an economic and psychometrically sound self
      report measure for the assessment of pathological dissociative phenomena.

PMID- 25584862
TI  - Multiscale modeling of a conditionally disordered pH-sensing chaperone.
AB  - The pH-sensing chaperone HdeA promotes the survival of enteropathogenic bacteria
      during transit through the harshly acidic environment of the mammalian stomach.
      At low pH, HdeA transitions from an inactive, folded, dimer to chaperone-active,
      disordered, monomers to protect against the acid-induced aggregation of
      periplasmic proteins. Toward achieving a detailed mechanistic understanding of
      the pH response of HdeA, we develop a multiscale modeling approach to capture its
      pH-dependent thermodynamics. Our approach combines pK(a) (logarithmic acid
      dissociation constant) calculations from all-atom constant pH molecular dynamics
      simulations with coarse-grained modeling and yields new, atomic-level, insights
      into HdeA chaperone function that can be directly tested by experiment. "pH
      triggers" that significantly destabilize the dimer are each located near the N
      terminus of a helix, suggesting that their neutralization at low pH destabilizes
      the helix macrodipole as a mechanism of monomer disordering. Moreover, we observe
      a non-monotonic change in the pH-dependent stability of HdeA, with maximal
      stability of the dimer near pH5. This affect is attributed to the protonation
      Glu37, which exhibits an anomalously high pK(a) value and is located within the
      hydrophobic dimer interface. Finally, the pH-dependent binding pathway of HdeA
      comprises a partially unfolded, dimeric intermediate that becomes increasingly
      stable relative to the native dimer at lower pH values and displays key
      structural features for chaperone-substrate interaction. We anticipate that the
      insights from our model will help inform ongoing NMR and biochemical
      investigations.

PMID- 25584864
TI  - [Functions of OCD - development and initial validation of a questionnaire (FFZ)].
AB  - The aim of this study was the development and psychometric assessment of a
      questionnaire for functions of OCD (FFZ). The instrument was analyzed using
      factor and item analyses with a sample of 120 OCD patients within the first 5
      weeks of an inpatient cognitive-behavioral treatment. The revealed scales were
      OCD as self-confirmation, emotion regulation, avoidance of responsibility,
      interpersonal regulation and OCD as occupation. The reliabilities of all
      subscales and the total value were satisfactory to nearly excellent. The
      factorial validity was good, content validity was excellent. The FFZ shows
      correlations with measures of interpersonal problems and emotional competence,
      but none with measures of self-reflection and therapy experience. No differences
      were found for gender or age. The results provide initial support for the
      reliability and validity of the FFZ. 

PMID- 25584861
TI  - Proteomic characterization of the nucleolar linker histone H1 interaction
      network.
AB  - To investigate the relationship between linker histone H1 and protein-protein
      interactions in the nucleolus, we used biochemical and proteomics approaches to
      characterize nucleoli purified from cultured human and mouse cells. Mass
      spectrometry identified 175 proteins in human T cell nucleolar extracts that
      bound to Sepharose-immobilized H1 in vitro. Gene ontology analysis found
      significant enrichment for H1 binding proteins with functions related to
      nucleolar chromatin structure and RNA polymerase I transcription regulation, rRNA
      processing, and mRNA splicing. Consistent with the affinity binding results, H1
      existed in large (400 to >650kDa) macromolecular complexes in human T cell
      nucleolar extracts. To complement the biochemical experiments, we investigated
      the effects of in vivo H1 depletion on protein content and structural integrity
      of the nucleolus using the H1 triple isoform knockout (H1DeltaTKO) mouse
      embryonic stem cell (mESC) model system. Proteomic profiling of purified wild
      type mESC nucleoli identified a total of 613 proteins, only ~60% of which were
      detected in the H1 mutant nucleoli. Within the affected group, spectral counting
      analysis quantitated 135 specific nucleolar proteins whose levels were
      significantly altered in H1DeltaTKO mESC. Importantly, the functions of the
      affected proteins in mESC closely overlapped with those of the human T cell
      nucleolar H1 binding proteins. Immunofluorescence microscopy of intact H1DeltaTKO
      mESC demonstrated both a loss of nucleolar RNA content and altered nucleolar
      morphology resulting from in vivo H1 depletion. We conclude that H1 organizes and
      maintains an extensive protein-protein interaction network in the nucleolus
      required for nucleolar structure and integrity. 

PMID- 25584865
TI  - [Psychotherapy on the domestic couch].
AB  - Despite the high morbidity of mental disorders in old age, psychotherapy take-up,
      especially by multi-morbid, very old patients, is still negligible, immobility
      being a significant constraining factor of access. So far, variations of standard
      psychotherapy adapted to meet these circumstances, such as home visits providing
      psychotherapy are not widespread and their effectiveness unexplored. An
      explorative study applying the 'Grounded Theory' method examined medical letters,
      consultation reports and session protocols of 7 psychotherapies involving 77-89
      year-old patients; it also described the setting, nature and content of the
      therapeutic relationship. Psychotherapy at a patient's home - compared with
      conventional out-patient therapy - considerably alters the therapeutic
      relationship in as much as an undifferentiated fullness of experience and
      information has to be gathered and interpreted by the therapist. Current and
      previous relationships, as well as the experience of disease and imminent dying
      are important thematic fields. Within the framework of a supportive, defence
      strengthening psychodynamic psychotherapy, clarifications, interpretations, and
      the accompaniment of existential conflicts and developments are possible.
      Conflicts of identity, aggression, closeness vs. distance and power can be named.
      Disease, constraint, dying and death are frequent topics. The therapist is more
      active, enactments are possible but a reflective attitude towards the patient's
      inner world can be maintained. Psychodynamic psychotherapy is possible in the
      patient's domestic environment. Further research on indications,
      psychotherapeutic attitudes, strategies, techniques and effectiveness of this
      psychotherapy variation is necessary. 

PMID- 25584866
TI  - Response-guided therapy for steroid-refractory acute GVHD starting with very-low
      dose antithymocyte globulin.
AB  - Treatment for steroid-refractory acute graft-versus-host disease (GVHD) has not
      been established yet. In this article, we report a single-center experience with
      rabbit antithymocyte globulin (ATG) for the treatment of steroid-refractory acute
      GVHD. We retrospectively analyzed 11 consecutive patients between December 2009
      and December 2013. ATG was given at an initial dose of 1.0 mg/kg for all but one
      patient with gradual dose escalation while assessing responses. The overall
      improvement at day 28 was 55% after a median of two treatments (range: 1-5), and
      a median dose of 3 mg/kg (range: 1.0-11.75 mg/kg) of ATG. Patients with skin
      (100%, 3/3) and gut (83%, 5/6) responded favorably, whereas the cases with liver
      involvement showed poor responses (25%, 1/4). The overall survival and transplant
      related mortality at 1 year were 55% and 45%, respectively. There were no
      patients who had developed a post-transplant lymphoproliferative disorder. We
      suggest that response-guided ATG therapy could be an option for patients with
      steroid-refractory GVHD, without increasing the incidence of opportunistic
      infections. 

PMID- 25584867
TI  - Antimalarial drug artemisinin depletes erythrocytes by activating apoptotic
      pathways in zebrafish.
AB  - Despite its extraordinary efficacy, administration of the major antimalarial drug
      artemisinin leads to anemia, and the underlying cellular and molecular mechanisms
      are not well understood. Here, we report the effects of artemisinin on erythroid
      development and apoptosis in zebrafish and human cells. By performing a small
      molecule screen with zebrafish embryos, we found that artemisinin treatment
      depleted red blood cells and slightly decreased definitive hematopoietic stem
      cells, but had no effect on primitive hematopoietic progenitors. RNA-Seq revealed
      that artemisinin suppressed a cluster of genes in the heme biosynthesis and
      globin synthesis pathways. Furthermore, artemisinin induced apoptosis in
      erythrocytes in zebrafish embryos, as assessed by terminal deoxynucleotidyl
      transferase dUTP nick end labeling assay, and preferentially acted on
      differentiated erythrocytes by elevating caspase 8 and caspase 9 activity in
      differentiated human K562 cells. Consistently, artemisinin suppressed the ectopic
      expression of erythroid genes in jak2aV581F-injected embryos, a zebrafish model
      for human polycythemia vera in which the bone marrow makes too many red blood
      cells. Taken together, our data suggested that artemisinin, in addition to
      killing parasites, has a direct action on differentiated erythrocytes other than
      definitive hematopoietic stem cells and causes erythroid apoptosis by interfering
      with the heme biosynthesis pathway in zebrafish and human cells.

PMID- 25584868
TI  - CD103 marks a subset of human CD34+-derived langerin+ dendritic cells that induce
      T-regulatory cells via indoleamine 2,3-dioxygenase-1.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive molecule expressed
      in some subsets of normal and neoplastic cells. Mature human dendritic cells
      (DCs) have been shown to express IDO1, but little is known about its expression
      and function during DC differentiation from bone marrow hematopoietic
      stem/progenitor cells (HSPCs). Here, we show that during in vitro differentiation
      along the myeloid DC lineage, CD34(+) HSPCs acquire IDO1 expression, which acts
      in a tolerogenic manner by inducing a population of fully functional
      CD4(+)CD25(+) FOXP3(+) T-regulatory cells. Phenotypically, CD1a(+)CD14(-) HPSC
      derived DCs expressed IDO1, langerin, CD11b, and CD1c. Cell-sorting experiments
      demonstrated that IDO1 expression is found in a subset of CD1a(+)CD14(
      )langerin(+) cells, expressing CD103, which is capable of inducing T-regulatory
      cells in an IDO1-dependent manner. In conclusion, DC differentiation from CD34(+)
      HSPCs results in the expression of a functionally active IDO1 protein in
      CD1a(+)langerin(+), CD103-expressing DCs. These data point toward IDO1 expression
      as part of a tolerogenic signature during DC development.

PMID- 25584870
TI  - Rat BMSCs initiate retinal endogenous repair through NGF/TrkA signaling.
AB  - Muller cells can completely repair retinal injury by acting as endogenous
      stem/progenitor cells in lower-order vertebrates. However, a safe and effective
      approach to activate progenitor potential of retinal Muller cells in higher-order
      vertebrates, which rarely re-enter the cell cycle, is a bottleneck problem. In
      the present study, Royal College of Surgeon's (RCS) rats were subjected to rat
      bone marrow mesenchymal stem cells (rBMSCs) subretinal space transplantation.
      Electroretinography (ERG) recordings showed that the b-wave amplitudes and ONL
      thicknesses statistically increased after transplantation. The number of Muller
      cells expressing proliferative, stem/progenitor and neuronal markers
      significantly increased after rBMSCs transplantation in vivo or after co
      culturing with rBMSCs in vitro. The cultured rBMSCs could secrete nerve growth
      factor (NGF). In addition, we confirmed that NGF or NGF-neutralizing antibody
      could activate or depress Muller cells dedifferentiation, both in vivo and in
      vitro. Furthermore, Muller cells expressing high levels of the NGF receptor
      neurotrophic tyrosine kinase receptor type 1 (TrkA) were observed in the retinas
      of rats transplanted with rBMSCs. Moreover, the protein expression of downstream
      elements of NGF/TrkA signaling, such as p-PI3K, p-Akt and p-CREB, increased in
      Muller cells in the retinas of rBMSCs-treated rats in vivo or in Muller cells co
      cultured with rBMSCs in vitro. Blocking TrkA with K-252a reduced the number of
      dedifferentiated Muller cells and the expression of NGF/TrkA signaling in vitro.
      Thus, rBMSCs might initiate endogenous regenerative mechanisms, which may
      constitute a new therapeutic strategy for retinal dystrophic diseases. 

PMID- 25584869
TI  - Isolation of microRNA from conjunctival impression cytology.
AB  - Impression cytology (IC) is an easy and safe technique that has been used in the
      past for harvesting epithelial cells from the cornea and conjunctiva for various
      applications including histology, immunohistology and molecular studies. Previous
      investigations have shown the usage of different types of membranes for the
      purpose of investigating pathophysiology and staging of diseases. This
      contributes to a better understanding of ocular surface conditions and helps to
      provide information for diagnosis, therapeutic options and prognosis. Recently,
      there has been a shift of focus in research towards understanding the
      contribution of microRNAs (miRs) to ocular disease. Thus far, impression cytology
      has been explored for measuring gene expression but not for quantifying miR
      expression. This study describes how miRs and mRNA can be isolated from
      conjunctival epithelial cells obtained by impression cytology and determines the
      optimum membrane and technique for this purpose. The IC technique was optimized
      using Biopore, Immobilon-P(SQ) and Millicell Hanging Cell Culture Insert
      membranes on healthy controls. miRs and mRNAs were isolated from the conjunctival
      epithelial cells (CEC) obtained and measured. Biopore membrane provided the
      optimum yield of miRs (38.8 ng/MUL +/- 10.8) and mRNA (155.3 ng/MUL +/- 20.1) as
      well as subjectively found to be best tolerated with minimum discomfort.
      Appreciable levels of miRs and mRNAs were detected from the CEC from healthy
      controls, confirming that it is possible to isolate miR and mRNA from CEC. Here,
      we give a detailed description of the application of conjunctival impression
      cytology to isolate miRs and the convenience of the technique by using the best
      membrane available. This method can be readily adopted in both clinical and
      laboratory settings. This technique will facilitate the measurement of miRs to
      improve our understanding of the pathogenesis of ocular surface conditions as
      well as potentially identifying novel therapeutic targets. 

PMID- 25584871
TI  - Synthesis of enantiomerically pure lignin dimer models for catalytic selectivity
      studies.
AB  - A series of highly enantioselective transformations, such as the Sharpless
      asymmetric epoxidation and Jacobsen hydrolytic kinetic resolution, were utilized
      to achieve the complete stereoselective synthesis of beta-O-4 lignin dimer models
      containing the S, G, and H subunits with excellent ee (>99%) and moderate to high
      yields. This unprecedented synthetic method can be exploited for enzymatic,
      microbial, and chemical investigations into lignin's degradation and
      depolymerization as related to its stereochemical constitution. Preliminary
      degradation studies using enantiopure Co(salen) catalysts are also reported. 

PMID- 25584872
TI  - Energy deficit does not affect immune responses of experimentally infected pacu
      (Piaractus mesopotamicus).
AB  - We investigated if the energy deficit following a 30-day starvation period could
      affect the ability of fish to mount immune responses after experimental exposure
      to Aeromonas hydrophila. Fish were submitted to two feeding strategies during 30
      days: starvation and continuously feeding. Fish were then sampled to allow for
      the assessment of baseline metabolic and immune system indicators, were next
      intraperitonially inoculated with A. hydrophila, and finally were sampled at 3
      and 24 h after the challenge. The respiratory activity of leukocytes was lower in
      starved fish at baseline, increasing after bacterial inoculation to levels
      similar to those seen among fed fish. Levels of serum lysozyme were higher in
      starved fish at baseline. The same response profile was observed 3 h after
      inoculation, but among fed fish, these levels increased to values similar to
      those of starved fish 24 h after infection. Among starved fish, lysozyme
      concentration did not change over the course of the experiment. The serum ACH
      activity was lower in starved fish at baseline and increased after bacterial
      inoculation in both fish groups. Baseline levels of blood glucose of starved fish
      were lower than those of fed fish and increased 3 h after bacterial inoculation
      in both fish groups, decreasing in both groups at 24 h after inoculation.
      Baseline liver glycogen levels were similar in both fish groups and higher than
      at 3 and 24 h after inoculation. Three hours after bacterial inoculation, liver
      glycogen was less reduced in fed fish. Baseline levels of blood triglycerides
      were lower in starved fish and the profile remained unchanged 3 h after
      inoculation. There was a gradual decrease in fed fish, and the levels of starved
      fish remained unchanged throughout the observation period. Blood glycerol levels
      at baseline were higher in starved fish than in fed fish and remained unaltered
      at 3 h after inoculation. However those levels increased at 24 h. In fed fish
      there was a gradual increase of glycerol levels up to 24 h after bacterial
      inoculation. Baseline liver lipid levels of starved fish were lower and this
      difference in the response profile remained unchanged 3 and 24 h after
      inoculation. The liver lipid levels of starved fish decreased after inoculation,
      and remained unchanged in fed fish. As observed in liver lipid, muscle lipid
      levels of starved fish were lower than in fed fish, throughout the experiment.
      Starved fish levels remained unchanged; however fed fish levels decreased 24 h
      after bacterial inoculation. Levels of cortisol were higher in starved fish at
      baseline and increased in both fish groups 3 h after bacterial inoculation,
      reaching intermediary levels 24 h after inoculation. Our results show that in
      pacu, although mounting an immune response triggered after bacterial exposure is
      an energy-expensive process, fish under energetic deficit status were able to
      display protection against infection. 

PMID- 25584873
TI  - Pre-gating conformational changes in the ChETA variant of channelrhodopsin-2
      monitored by nanosecond IR spectroscopy.
AB  - Light-gated ion permeation by channelrhodopsin-2 (ChR2) relies on the
      photoisomerization of the retinal chromophore and the subsequent photocycle,
      leading to the formation (on-gating) and decay (off-gating) of the conductive
      state. Here, we have analyzed the photocycle of a fast-cycling ChR2 variant
      (E123T mutation, also known as ChETA), by time-resolved UV/vis, step-scan FT-IR,
      and tunable quantum cascade laser IR spectroscopies with nanosecond resolution.
      Pre-gating conformational changes rise with a half-life of 200 ns, silent to
      UV/vis but detected by IR spectroscopy. They involve changes in the peptide
      backbone and in the H-bond of the side chain of the critical residue D156. Thus,
      the P1(500) intermediate must be separated into early and late states. Light
      adapted ChR2 contains a mixture of all-trans and 13-cis retinal in a 70:30 ratio
      which are both photoactive. Analysis of ethylenic and fingerprint vibrations of
      retinal provides evidence that the 13-cis photocycle recovers in 1 ms. This
      recovery is faster than channel off-gating and most of the proton transfer
      reactions, implying that the 13-cis photocycle is of minor functional relevance
      for ChR2. 

PMID- 25584874
TI  - [Managing return to work versus absenteeism control].

PMID- 25584875
TI  - [Archivos de Prevencion 2014: another year with changes].

PMID- 25584876
TI  - [Description of dysphonia cases assisted in a mutua in 2013].
AB  - OBJECTIVE: To describe a case series of patients with dysphonia evaluated in a
      national Spanish mutua. METHODS: Computerized medical records of 2013 were
      reviewed and 129 patients with diagnoses compatible with dysphonia were
      identified. RESULTS: Eighty-six (67%) of the 129 cases were recognized as
      occupational diseases, three cases were considered as occupational injuries (two
      with a diagnosis of Reinke's edema) and the remaining 40 cases were considered to
      not be work-related. Most of the cases (90%) occurred in women between the ages
      of 30 and 49 years. Ninety-three percent of the cases diagnosed as occupational
      diseases underwent speech therapy and, of these, 72% were cured. The majority of
      the cases (61%) occurred in teachers. Average duration of sickness absence, among
      those patients who took it, was 113.5 days. CONCLUSIONS: All cases reported as
      occupational disease met the criteria set by the Spanish legislation (RD
      1299/2006). Non-occupational diseases were referred to the national health
      service. Customized speech therapy was effective for most of the patients. The
      average duration of sick leave in our series was high.

PMID- 25584877
TI  - [Anorexia nervosa in a worker: a case report].
AB  - We describe the management of a case of anorexia nervosa (body mass index, -BMI-,
      13,6 Kg/m2) in a bank teller. The case was detected through routine occupational
      health surveillance. After being evaluated by different specialists (general
      practitioner, psychiatrist and endocrinologist) and being closely monitored (by
      psychology, nursing, and occupational medicine), the worker regained weight to a
      near normal BMI (17 Kg/m2) in less than a year and a half. Eating disorders are a
      common pathology (non-occupationally related), but their high prevalence (5% of
      the population over a lifetime) and social and job-related impact (affecting more
      than 20% of cases), make them a necessary focus of attention for health promotion
      in the workplace. Health prevention, promotion and surveillance may be also
      reinforced at the workplace. 

PMID- 25584878
TI  - [Health workers and latex allergy].

PMID- 25584879
TI  - [Work-related contingencies in different situations of infection by Ebola virus].

PMID- 25584880
TI  - Isolation of norsesterterpenes and spongian diterpenes from Dorisprismatica (=
      Glossodoris) atromarginata.
AB  - Ten new norscalarane metabolites (1-10) with the mooloolabene skeleton in which
      the C-8 methyl substituent of a scalarane is replaced by a C-7/C-8 double bond
      are described from the nudibranch Doriprismatica (= Glossodoris) atromarginata
      and characterized by extensive 1D and 2D NMR studies, together with MS data. Also
      isolated was the known scalarane 12-deacetoxy-12-oxo-deoxoscalarin together with
      26 furanoterpenes, nine of which (11-19) are reported for the first time. The
      high diversity of chemical compounds and variation between individuals and
      locations could reflect a varied sponge diet or an enzymatic detoxification
      mechanism.

PMID- 25584881
TI  - Theoretical study of the reaction kinetics of atomic bromine with
      tetrahydropyran.
AB  - A detailed theoretical analysis of the reaction of atomic bromine with
      tetrahydropyran (THP, C5H10O) was performed using several ab initio methods and
      statistical rate theory calculations. Initial geometries of all species involved
      in the potential energy surface of the title reaction were obtained at the
      B3LYP/cc-pVTZ level of theory. These molecular geometries were reoptimized using
      three different meta-generalized gradient approximation (meta-GGA) functionals.
      Single-point energies of the stationary points were obtained by employing the
      coupled-cluster with single and double excitations (CCSD) and fourth-order Moller
      Plesset (MP4 SDQ) levels of theory. The computed CCSD and MP4(SDQ) energies for
      optimized structures at various DFT functionals were found to be consistent
      within 2 kJ mol(-1). For a more accurate energetic description, single-point
      calculations at the CCSD(T)/CBS level of theory were performed for the minimum
      structures and transition states optimized at the B3LYP/cc-pVTZ level of theory.
      Similar to other ether + Br reactions, it was found that the tetrahydropyran + Br
      reaction proceeds in an overall endothermic addition-elimination mechanism via a
      number of intermediates. However, the reactivity of various ethers with atomic
      bromine was found to vary substantially. In contrast with the 1,4-dioxane + Br
      reaction, the chair form of the addition complex (c-C5H10O-Br) for THP + Br does
      not need to undergo ring inversion to form a boat conformer (b-C4H8O2-Br) before
      the intramolecular H-shift can occur to eventually release HBr. Instead, a
      direct, yet more favorable route was mapped out on the potential energy surface
      of the THP + Br reaction. The rate coefficients for all relevant steps involved
      in the reaction mechanism were computed using the energetics of coupled cluster
      calculations. On the basis of the results of the CCSD(T)/CBS//B3LYP/cc-pVTZ level
      of theory, the calculated overall rate coefficients can be expressed as
      kov.,calc.(T) = 4.60 * 10(-10) exp[-20.4 kJ mol(-1)/(RT)] cm(3) molecule(-1) s(
      1) for the temperature range of 273-393 K. The calculated values are found to be
      in excellent agreement with the experimental data published previously. 

PMID- 25584883
TI  - N-heterocyclic carbene-catalyzed diastereoselective and enantioselective reaction
      of 2-aroylvinylcinnamaldehydes with alpha,beta-unsaturated imines: complete
      control and switch of diastereoselectivity by N-substituents of catalysts.
AB  - Highly diastereoselective and enantioselective reactions between 2
      aroylvinylcinnamaldehydes and alpha,beta-unsaturated imines were achieved under
      asymmetric catalysis of chiral triazole carbene catalysts. In the presence of N
      anisylindeno[2,1-b]triazolo[4,3-d][1,4]oxazinium salt, the reaction of 2
      aroylvinylcinnamaldehydes with alpha,beta-unsaturated imines afforded indeno[2,1
      c]pyran-1-one derivatives 4 with 90%-99% ee, while enantiopure indenocyclopentan
      1-ones 5 (>99% ee) were obtained under the catalysis of N-mesitylindeno[2,1
      b]triazolo[4,3-d][1,4]oxazinium salt. A slight variation of an N-substituent on
      triazole carbenes was found to switch completely the diastereoselectivity of the
      reaction for the formation of indeno[2,1-c]pyran-1-ones. 

PMID- 25584882
TI  - Bioanalysis of 6-diazo-5-oxo-l-norleucine in plasma and brain by ultra
      performance liquid chromatography mass spectrometry.
AB  - Glutamine is an abundant amino acid that plays pivotal roles in cell growth, cell
      metabolism, and neurotransmission. Dysregulation of glutamine-using pathways has
      been associated with pathological conditions such as cancer and neurodegenerative
      diseases. 6-Diazo-5-oxo-l-norleucine (DON) is a reactive glutamine analog that
      inhibits enzymes affecting glutamine metabolism such as glutaminase, 2-N
      amidotransferase, l-asparaginase, and several enzymes involved in pyrimidine and
      purine de novo synthesis. As a result, DON is actively used in preclinical models
      of cancer and neurodegenerative disease. Moreover, there have been several
      clinical trials using DON to treat a variety of cancers. Considerations of dose
      and exposure are especially important with DON treatment due to its narrow
      therapeutic window and significant side effects. Consequently, a robust
      quantification bioassay is of interest. DON is a polar unstable molecule that has
      made quantification challenging. Here we report on the characterization of a
      bioanalytical method to quantify DON in tissue samples involving DON
      derivatization with 3 N HCl in butanol. The derivatized product is lipophilic and
      stable. Detection of this analyte by mass spectrometry is fast and specific and
      can be used to quantify DON in plasma and brain tissue with a limit of detection
      at the low nanomolar level.

PMID- 25584884
TI  - Celebrating Bidleman's 1988 "atmospheric processes".

PMID- 25584885
TI  - In-hospital management of children with bacterial meningitis in Italy.
AB  - BACKGROUND: Over the years 2009-2013, we conducted a prospective study within a
      network established by the Italian Society of Pediatrics to describe the in
      hospital management of children hospitalized for acute bacterial meningitis in 19
      Italian hospitals with pediatric wards. METHODS: Hospital adherence to the study
      was voluntary; data were derived from clinical records. Information included
      demographic data, dates of onset of first symptoms, hospitalization and
      discharge; diagnostic evaluation; etiology; antimicrobial treatment; treatment
      with dexamethasone; in-hospital complications; neurological sequelae and status
      at hospital discharge. Characteristics of in-hospital management of patients were
      described by causative agent. RESULTS: Eighty-five patients were identified;
      49.4% had received an antimicrobial treatment prior to admission. Forty percent
      of patients were transferred from other Centers; the indication to seek for
      hospital care was given by the primary care pediatrician in 80% of other
      children. Etiological agent was confirmed in 65.9% of cases; the most common
      infectious organism was Neisseria meningitidis (34.1%), followed by Streptococcus
      pneumoniae (20%). Patients with pneumococcal meningitis had a significant longer
      interval between onset of first symptoms and hospital admission. Median interval
      between the physician suspicion of meningitis and in-hospital first antimicrobial
      dose was 1 hour (interquartile range [IQR]: 1-2 hours). Corticosteroids were
      given to 63.5% of cases independently of etiology; 63.0% of treated patients
      received dexamethasone within 1 hour of antibiotic treatment, and 41.2% were
      treated for <=4 days. Twenty-nine patients reported at least one in-hospital
      complication (34.1%). Six patients had neurological sequelae at discharge (7.1%).
      No deaths were observed. CONCLUSIONS: We observed a rate of meningitis sequelae
      at discharge similar to that reported by other western countries. Timely
      assistance and early treatment could have contributed to the favorable outcome
      that was observed in the majority of cases. Adherence to recommendation for
      corticosteroid adjunctive therapy seems suboptimal, and should be investigated in
      further studies. Most meningitis cases were due to N. meningitidis and S.
      pneumoniae. Reaching and maintaining adequate vaccination coverage against
      pneumococcal and meningococcal invasive infections remains a priority to prevent
      bacterial meningitis cases.

PMID- 25584886
TI  - Common TLR5 mutations control cancer progression.
AB  - The mechanisms regulating tumor-associated inflammation are incompletely
      understood. In this issue of Cancer Cell, Rutkowski and colleagues indicate that
      TLR5 signaling deficiency, which occurs in ~10% of the population, changes
      interactions with commensal microbiota and deregulates a cascade of inflammatory
      events that can suppress or accelerate extraintestinal cancers. 

PMID- 25584887
TI  - mTOR signaling in melanoma: oncogene-induced pseudo-senescence?
AB  - Oncogene-induced senescence (OIS) is thought to be a barrier to malignant
      transformation resulting from the strong activation of oncogenes. In this issue
      of Cancer Cell, Damsky and colleagues suggest activation of mTORC1 and mTORC2 is
      required for OIS evasion in human melanomas harboring oncogenic BRAF mutations. 

PMID- 25584888
TI  - Breaking up is hard to do: PI3K isoforms on the rebound.
AB  - In this issue of Cancer Cell, Schwartz and colleagues and Costa and colleagues
      demonstrate that inhibition of PI3Kalpha or PI3Kbeta in cancer cells with
      hyperactivated PI3Kalpha or PI3Kbeta, respectively, activates the other isoform,
      leading to a "rebound" of the PI3K activity through different compensation
      mechanisms. 

PMID- 25584890
TI  - No need for constant help: human IgG2 antibodies have an autonomous agonistic
      activity for immunotherapy of cancer.
AB  - Agonistic antibodies specific for members of the tumor necrosis factor receptor
      protein family hold great promise for immunotherapy of cancer. In this issue of
      Cancer Cell, White and colleagues provide evidence that the human IgG2 subclass
      may represent a superior backbone for the use of these antibodies in human
      therapy. 

PMID- 25584889
TI  - Vascular-promoting therapy reduced tumor growth and progression by improving
      chemotherapy efficacy.
AB  - In this issue of Cancer Cell, Wong and colleagues describe a novel approach of
      increasing the number of functional blood vessels in tumors using a low-dose
      therapy regimen of Cilengtide and Verapamil. This method enhanced gemcitabine
      delivery, uptake, and metabolism within tumor cells to reduce tumor growth and
      progression.

PMID- 25584891
TI  - Biomarkers in cancer immunotherapy.
AB  - Antibodies against T cell checkpoint molecules have started to revolutionize
      cancer treatment. Nevertheless, less than half of all patients respond to these
      immunotherapies. Recent work supports the potential value of biomarkers that
      predict therapy outcome and inspires the development of assay systems that
      interrogate other aspects of the cancer-immunity cycle.

PMID- 25584892
TI  - Biological and therapeutic impact of intratumor heterogeneity in cancer
      evolution.
AB  - Precision medicine requires an understanding of cancer genes and mutational
      processes, as well as an appreciation of the extent to which these are found
      heterogeneously in cancer cells during tumor evolution. Here, we explore the
      processes shaping the cancer genome, placing these within the context of tumor
      evolution and their impact on intratumor heterogeneity and drug development. We
      review evidence for constraints and contingencies to tumor evolution and
      highlight the clinical implications of diversity within tumors. We outline the
      limitations of genome-driven targeted therapies and explore future strategies,
      including immune and adaptive approaches, to address this therapeutic challenge. 

PMID- 25584893
TI  - mTORC1 activation blocks BrafV600E-induced growth arrest but is insufficient for
      melanoma formation.
AB  - Braf(V600E) induces benign, growth-arrested melanocytic nevus development, but
      also drives melanoma formation. Cdkn2a loss in Braf(V600E) melanocytes in mice
      results in rare progression to melanoma, but only after stable growth arrest as
      nevi. Immediate progression to melanoma is prevented by upregulation of miR
      99/100, which downregulates mTOR and IGF1R signaling. mTORC1 activation through
      Stk11 (Lkb1) loss abrogates growth arrest of Braf(V600E) melanocytic nevi, but is
      insufficient for complete progression to melanoma. Cdkn2a loss is associated with
      mTORC2 and Akt activation in human and murine melanocytic neoplasms. Simultaneous
      Cdkn2a and Lkb1 inactivation in Braf(V600E) melanocytes results in activation of
      both mTORC1 and mTORC2/Akt, inducing rapid melanoma formation in mice. In this
      model, activation of both mTORC1/2 is required for Braf-induced melanomagenesis. 

PMID- 25584896
TI  - Loop contributions to the folding thermodynamics of DNA straight hairpin loops
      and pseudoknots.
AB  - Pseudoknots have diverse and important roles in many biological functions. We
      used a combination of UV spectroscopy and differential scanning calorimetry to
      investigate the effect of the loop length on the unfolding thermodynamics of
      three sets of DNA stem-loop motifs with the following sequences: (a)
      d(GCGCTnGCGC), where n = 3, 5, 7, 9; (b) d(CGCGCGT4GAAATTCGCGCGTnAATTTC), where n
      = 4, 6, and 8; and (c) d(TCTCTTnAAAAAAAAGAGAT5TTTTTTT), where n = 5, 7, 9, and
      11. The increase in loop length of the first set of hairpins yielded decreasing
      TM's and constant unfolding enthalpies, resulting in an entropy driven decrease
      in the stability of the hairpin (DeltaG degrees  = -7.5 to -6.1 kcal/mol). In the
      second set, the increase in the length of the loops yielded similar TM's and
      slight increases in the unfolding enthalpies. This translated into more stable
      pseudoknots with an increasing DeltaG degrees  from -13.2 to -17.1 kcal/mol. This
      effect can be rationalized in terms of the increased flexibility of the
      pseudoknot with larger loops optimizing base-pair stacking interactions. In the
      last set of molecules, the increase in the length of one of the loops yielded an
      increase in the TM's and larger increases in the enthalpies, which stabilize the
      pseudoknot significantly increasing the DeltaG degrees  from -8.5 to -16.6
      kcal/mol. In this set, the thymine loop is complementary to the stem of A.T base
      pairs and the longer loops are able to form T*A.T base triplets due to the
      partial folding of the thymine loop into the ceiling of the major groove of the
      duplex, thus yielding a net formation of 1-3 T*AT/T*AT base-triplet stacks at the
      middle of its stem, depending on the loop length. 

PMID- 25584895
TI  - Dual-action combination therapy enhances angiogenesis while reducing tumor growth
      and spread.
AB  - Increasing chemotherapy delivery to tumors, while enhancing drug uptake and
      reducing side effects, is a primary goal of cancer research. In mouse and human
      cancer models in vivo, we show that coadministration of low-dose Cilengitide and
      Verapamil increases tumor angiogenesis, leakiness, blood flow, and Gemcitabine
      delivery. This approach reduces tumor growth, metastasis, and minimizes side
      effects while extending survival. At a molecular level, this strategy alters
      Gemcitabine transporter and metabolizing enzyme expression levels, enhancing the
      potency of Gemcitabine within tumor cells in vivo and in vitro. Thus, the dual
      action of low-dose Cilengitide, in vessels and tumor cells, improves chemotherapy
      efficacy. Overall, our data demonstrate that vascular promotion therapy is a
      means to improve cancer treatment. 

PMID- 25584894
TI  - Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell
      growth under metabolic stress.
AB  - A functional genomics study revealed that the activity of acetyl-CoA synthetase 2
      (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted
      conditions. Comparative metabolomics and lipidomics demonstrated that acetate is
      used as a nutritional source by cancer cells in an ACSS2-dependent manner, and
      supplied a significant fraction of the carbon within the fatty acid and
      phospholipid pools. ACSS2 expression is upregulated under metabolically stressed
      conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2
      exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates
      with disease progression. These results signify a critical role for acetate
      consumption in the production of lipid biomass within the harsh tumor
      microenvironment. 

PMID- 25584897
TI  - Effects of methadone plus alcohol on cognitive performance in methadone
      maintained volunteers.
AB  - BACKGROUND: Methadone maintenance patients (MMP) often abuse other drugs,
      including alcohol. The combined use of methadone and alcohol could impair
      performance and daily functioning. OBJECTIVE: To examine the effects of methadone
      in combination with alcohol, as well as acute increases in methadone, on
      performance outcomes. METHODS: This double-blind, double-dummy, crossover study
      included eight opioid-dependent participants stabilized on methadone.
      Participants completed six inpatient sessions corresponding to methadone (100% or
      150% of daily dose) and beverage (placebo, 0.25 or 0.50 g/kg alcohol).
      Performance tasks were completed before and after drug administration. Area under
      the time-course values were analyzed by a 2 (methadone dose) by 3 (alcohol dose)
      repeated measures analysis of variance. RESULTS: Main effects of methadone were
      observed for two attention outcomes, suggesting reduced accuracy and slowed
      responding at an elevated methadone dose. In addition, main effects of alcohol
      were observed for episodic memory (false alarms and response bias) suggesting
      more impulsive responding as alcohol dose increased. No robust interactions of
      methadone and alcohol were observed for any outcome. CONCLUSIONS: Study findings
      indicate that an acute increase in methadone (150%) and a moderate dose of
      alcohol (2-3 drinks) can impair distinct aspects of performance, although no
      significant interactive effect between methadone and alcohol was found. Future
      studies with larger sample sizes, larger doses, and more clinically informative
      tasks could expand on the present findings and further explore the cognitive
      consequences of concurrent opioid and alcohol use.

PMID- 25584899
TI  - Preparation of Small RNAs Using Rolling Circle Transcription and Site-Specific
      RNA Disconnection.
AB  - A facile and robust RNA preparation protocol was developed by combining rolling
      circle transcription (RCT) with RNA cleavage by RNase H. Circular DNA with a
      complementary sequence was used as the template for promoter-free transcription.
      With the aid of a 2'-O-methylated DNA, the RCT-generated tandem repeats of the
      desired RNA sequence were disconnected at the exact end-to-end position to
      harvest the desired RNA oligomers. Compared with the template DNA, more than 4 *
      10(3) times the amount of small RNA products were obtained when modest cleavage
      was carried out during transcription. Large amounts of RNA oligomers could easily
      be obtained by simply increasing the reaction volume. 

PMID- 25584898
TI  - A pathogenetic role for IL-21 in primary Sjogren syndrome.
AB  - Advances in our understanding of the pathogenesis of primary Sjogren syndrome
      (pSS) characterize it as a highly complex process encompassing both the
      initiation of innate immunity and subsequent adaptive immune responses. IL-21 is
      receiving attention as a potential key player in the pathogenesis of pSS owing to
      its pleiotropic effects on the type I interferon signalling pathway, and newly
      identified roles in generation of follicular and IL-17-producing subtypes of
      helper T cells, as well as plasma-cell differentiation and B-cell activation.
      Taking into consideration the diverse biological functions of IL-21 and its
      clinical relevance to pSS, we propose that this cytokine has a central role in
      orchestrating the complex immune response in pSS. This hypothesis might provide
      new insight into the pathogenesis of pSS and facilitate the development of
      effective therapeutic strategies.

PMID- 25584901
TI  - Continuous wave blue lasing in III-nitride nanobeam cavity on silicon.
AB  - III-V photonics on silicon is an active and promising research area. Here, we
      demonstrate room-temperature (RT) lasing in short-wavelength III-nitride photonic
      crystal nanobeam cavities grown on silicon featuring a single InGaN quantum well
      (QW). In the low-absorption QW region, high quality factors in excess of 10(4)
      are measured, while RT blue lasing under continuous-wave optical pumping is
      reported in the high-absorption wavelength range, hence the high QW gain region.
      Lasing characteristics are well accounted for by the large spontaneous emission
      coupling factor (beta > 0.8) inherent to the nanobeam geometry and the large
      InGaN QW material gain. Our work illustrates the high potential of III-nitrides
      on silicon for the realization of low power nanophotonic devices with a reduced
      footprint that would be of prime interest for fundamental light-matter
      interaction studies and a variety of lab-on-a-chip applications including
      biophotonics. 

PMID- 25584900
TI  - Chimeric Antisense Oligonucleotide Conjugated to alpha-Tocopherol.
AB  - We developed an efficient system for delivering short interfering RNA (siRNA) to
      the liver by using alpha-tocopherol conjugation. The alpha-tocopherol-conjugated
      siRNA was effective and safe for RNA interference-mediated gene silencing in
      vivo. In contrast, when the 13-mer LNA (locked nucleic acid)-DNA gapmer antisense
      oligonucleotide (ASO) was directly conjugated with alpha-tocopherol it showed
      markedly reduced silencing activity in mouse liver. Here, therefore, we tried to
      extend the 5'-end of the ASO sequence by using 5'-alpha-tocopherol-conjugated 4-
      to 7-mers of unlocked nucleic acid (UNA) as a "second wing." Intravenous
      injection of mice with this alpha-tocopherol-conjugated chimeric ASO achieved
      more potent silencing than ASO alone in the liver, suggesting increased delivery
      of the ASO to the liver. Within the cells, the UNA wing was cleaved or degraded
      and alpha-tocopherol was released from the 13-mer gapmer ASO, resulting in
      activation of the gapmer. The alpha-tocopherol-conjugated chimeric ASO showed
      high efficacy, with hepatic tropism, and was effective and safe for gene
      silencing in vivo. We have thus identified a new, effective LNA-DNA gapmer
      structure in which drug delivery system (DDS) molecules are bound to ASO with UNA
      sequences. 

PMID- 25584903
TI  - A redox-flow electrochromic window.
AB  - A low-cost electrochromic (EC) window based on a redox-flow system that does not
      require expensive transparent conductive oxide (TCO) substrates is introduced and
      demonstrated for the first time. An aqueous I3-/I- redox electrolyte is used in
      place of a TCO to oxidize/reduce a molecular layer of an EC triphenylamine
      derivative that is anchored to a mesoporous TiO2 scaffold on the inner faces of a
      double-paned window. The redox electrolyte is electrochemically oxidized/reduced
      in an external two-compartment cell and circulated through the window cavity
      using an inexpensive peristaltic pump, resulting in coloration or decoloration of
      the window due to reaction of the redox solution with the triphenylamine
      derivative. The absorption characteristics, coloration/decoloration times, and
      cycling stability of the prototype EC window are evaluated, and prospects for
      further development are discussed.

PMID- 25584902
TI  - Requirements for mutant and wild-type prion protein misfolding in vitro.
AB  - Misfolding of the prion protein (PrP) plays a central role in the pathogenesis of
      infectious, sporadic, and inherited prion diseases. Here we use a chemically
      defined prion propagation system to study misfolding of the pathogenic PrP mutant
      D177N in vitro. This mutation causes PrP to misfold spontaneously in the absence
      of cofactor molecules in a process dependent on time, temperature, pH, and
      intermittent sonication. Spontaneously misfolded mutant PrP is able to template
      its unique conformation onto wild-type PrP substrate in a process that requires a
      phospholipid activity distinct from that required for the propagation of
      infectious prions. Similar results were obtained with a second pathogenic PrP
      mutant, E199K, but not with the polymorphic substitution M128V. Moreover, wild
      type PrP inhibits mutant PrP misfolding in a dose-dependent manner, and cofactor
      molecules can antagonize this effect. These studies suggest that interactions
      between mutant PrP, wild-type PrP, and other cellular factors may control the
      rate of PrP misfolding in inherited prion diseases. 

PMID- 25584905
TI  - Cardiac Telocytes.
AB  - Telocytes (TCs), are a specific type of stromal cells, with a characteristic
      appearance including a small cell body and very long and thin telopodes. TCs have
      been reportedly identified in almost all human organs and tissues, including
      heart, pulmonary veins, and intestine. Cardiac TCs are widely distributed in the
      endocardium, epicardium, myocardium, and even stem cell niches. In physiological
      conditions, TCs form a three-dimensional architecture through homocellular and
      heterocellular interactions and stimulate the growth and differentiation of
      cardiac progenitor/stem cells during organogenesis. In pathological conditions,
      TCs improve cardiac function by contributing to cardiomyocyte renewal, enhancing
      angiogenesis, and decreasing cardiac fibrosis. Our understanding suggests these
      cells could lead to their use a source of cellular therapy to enhance repair of
      damaged myocardium. This review summarizes recent progress on the potential
      biological function of TCs in cardiac physiology and disease. Although TCs have
      beneficial effects towards cardiac injury, the molecular mechanisms whereby these
      effects are accomplished remain unclear. Additional in vivo functional studies on
      TCs will help improve our understanding of the mechanism by which TCs contribute
      to cardiac repair. 

PMID- 25584904
TI  - Genome wide chromatin occupancy of mrhl RNA and its role in gene regulation in
      mouse spermatogonial cells.
AB  - Mrhl RNA is a nuclear lncRNA encoded in the mouse genome and negatively regulates
      Wnt signaling in spermatogonial cells through p68/Ddx5 RNA helicase. Mrhl RNA is
      present in the chromatin fraction of mouse spermatogonial Gc1-Spg cells and
      genome wide chromatin occupancy of mrhl RNA by ChOP (Chromatin oligo affinity
      precipitation) technique identified 1370 statistically significant genomic loci.
      Among these, genes at 37 genomic loci also showed altered expression pattern upon
      mrhl RNA down regulation which are referred to as GRPAM (Genes Regulated by
      Physical Association of Mrhl RNA). p68 interacted with mrhl RNA in chromatin at
      these GRPAM loci. p68 silencing drastically reduced mrhl RNA occupancy at 27
      GRPAM loci and also perturbed the expression of GRPAM suggesting a role for p68
      mediated mrhl RNA occupancy in regulating GRPAM expression. Wnt3a ligand
      treatment of Gc1-Spg cells down regulated mrhl RNA expression and also perturbed
      expression of these 27 GRPAM genes that included genes regulating Wnt signaling
      pathway and spermatogenesis, one of them being Sox8, a developmentally important
      transcription factor. We also identified interacting proteins of mrhl RNA
      associated chromatin fraction which included Pc4, a chromatin organizer protein
      and hnRNP A/B and hnRNP A2/B1 which have been shown to be associated with lincRNA
      Cox2 function in gene regulation. Our findings in the Gc1-Spg cell line also
      correlate with the results from analysis of mouse testicular tissue which further
      highlights the in vivo physiological significance of mrhl RNA in the context of
      gene regulation during mammalian spermatogenesis. 

PMID- 25584907
TI  - Unconventional Players on the Striated Muscle Field: microRNAs, Signaling
      Pathways and Epigenetic Regulators.
AB  - Striated muscle regeneration holds an intrinsic complexity governed by many
      orchestrated events. When the fine balance of regulatory machineries is under
      strain, the homeostatic conditions are lost and degeneration starts to occur.
      This is the case for inherited and acquired diseases of both cardiac and skeletal
      muscles. A wide range of factors are currently under scrutiny for better
      understanding the details underlying de-/re-generation processes, of both genetic
      and non-genetic nature. This review focuses on three classes of non-genetic
      factors regulating striated muscle regeneration, i.e. microRNAs, signaling
      pathways and epigenetic regulators. 

PMID- 25584908
TI  - Environmental exposure, allergic disease and asthma: the distinguishing hallmark
      of allergy-immunology.

PMID- 25584909
TI  - Atopic dermatitis: the updated practice parameter and beyond.
AB  - An update to the atopic dermatitis (AD) practice parameter was published in 2013
      using an established grading system for determining category of evidence and
      strength of recommendation. Since the previous update in 2004, a number of
      seminal observations regarding skin barrier and immune dysregulation in AD have
      been made with important therapeutic implications. A key addition to the
      treatment algorithm based on our understanding that normal-appearing skin in
      patients with AD is not normal is proactive therapy. Studies with both topical
      steroids and a topical calcineurin inhibitor have shown that in patients with
      relapsing AD, if they are able to clear or almost clear their eczema, then twice
      weekly proactive treatment of normal-appearing skin that tends to flare leads to
      better disease control. For difficult-to-manage patients, the value of wet wrap
      therapy is reaffirmed in the practice parameter update. In addition, allergen
      immunotherapy is now a consideration in select patients with AD and aeroallergen
      sensitivity. Beyond the practice parameter, novel approaches to filaggrin
      deficiency are being evaluated. With respect to immune dysregulation, dupilumab,
      a fully human monoclonal antibody directed at the IL-4 receptor alpha subunit was
      recently shown to be effective in treating adults with moderate-to-severe AD. 

PMID- 25584910
TI  - Atopy patch testing for foods: a review of the literature.
AB  - The atopy patch test (APT) was first reported in 1895 by the German
      dermatologist, Jadassohn and was used for evaluation of contact dermatitis. The
      first documented epicutaneous application of aeroallergens was by Rostenberg and
      Sulzbergen in 1937. Although others including Mitchell and Platts-Mills, further
      described patch testing with aeroallergens, Langeland et al. initially described
      the use of patch testing with foods by testing atopic patients against egg white.
      Subsequently, food patch testing has gained popularity and has been included as a
      potential test to assess for food allergy not only for atopic dermatitis (AD) but
      also eosinophilic esophagitis and food protein-induced enterocolitis syndrome,
      although its role still remains unclear. Through a comprehensive literature
      review, this article addresses the use of APT for foods and its application in AD
      and other allergic diseases. There will be inclusion of some data from
      aeroallergen and hapten patch testing as a basis from which our knowledge for
      food APT is derived. The data, in particular the sensitivity, specificity, and
      predictive values, vary widely from 0 to 100%, depending on the study. Given this
      large variation in test results, food APT use in isolation is not recommended at
      this time. Additional studies are needed to standardize, improve accuracy and
      reproducibility, and determine its role in the evaluation of allergic diseases. 

PMID- 25584906
TI  - Understanding nucleus pulposus cell phenotype: a prerequisite for stem cell based
      therapies to treat intervertebral disc degeneration.
AB  - Intervertebral disc (IVD) degeneration and associated low back pain (LBP) remains
      a major burden to our society without significant improvements in treatment
      strategies or patient's quality of life. While the recent cell-transplantation
      studies for treatment of degenerative disc disease have shown promising results,
      to better gauge the success and functional outcomes of these therapies, it is
      crucial to understand if transplanted cells give rise to healthy nucleus pulposus
      (NP) tissue. NP cell phenotype is unique and is defined by expression of a
      characteristic set of markers that reflect specialized physiology and function.
      This review summarizes phenotypic markers that mirror the unique physiology and
      function of NP cells and their progenitors and should be considered to when
      measuring outcomes of cell-based therapies to treat disc degeneration. 

PMID- 25584911
TI  - The thrombogenicity of C1 esterase inhibitor (human): review of the evidence.
AB  - Thromboembolic events associated with human plasma-derived C1 esterase inhibitor
      (C1-INH) use in patients with hereditary angioedema (HAE) have been reported in
      the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System
      database. The purpose of this article is to review and assess the strength of
      available evidence regarding the thrombogenicity of human plasma-derived C1-INH.
      A PubMed search was conducted of English language articles from January 1990 to
      December 2013 reporting the thrombogenicity of C1-INH. Original research articles
      were selected if the following criteria were met: (1) C1-INH was the focus of the
      study and (2) the authors addressed the pro- or antithrombotic potential of C1
      INH. Additional articles on the clinical use of C1-INH in disease states other
      than HAE were obtained using reference lists of selected articles. Pivotal
      studies and prescribing information for C1-INH products were also reviewed.
      Limited animal and clinical data suggest that C1-INH, particularly at high doses
      of up to 500 U/kg (compared with the U.S. FDA-approved 20-U/kg dose), may be
      prothrombotic. In contrast, C1-INH has been used in some patients with myocardial
      infarction, ischemic stroke, sepsis, and capillary leak syndrome at off-label
      supratherapeutic doses (up to 100 U/kg) without evidence of a thrombogenic
      effect. Based on our review, thromboembolic events reported with C1-INH use are
      rare and patients with HAE who experienced such events often have underlying
      thromboembolic risk factors. 

PMID- 25584912
TI  - Smoke exposure as a risk factor for asthma in childhood: a review of current
      evidence.
AB  - Asthma is a common chronic multifactorial disease that affects >300 million
      people worldwide. Outdoor and indoor pollution exposure has been associated with
      respiratory health effects in adults and children. Smoking still represents a
      huge public health problem and millions of children suffer the detrimental
      effects of passive smoke exposure. This study was designed to review the current
      evidences on exposure to passive smoke as a risk factor for asthma onset in
      childhood. A review of the most recent studies on this topic was undertaken to
      provide evidence about the magnitude of the effect of passive smoking on the risk
      of incidence of asthma in children. The effects of passive smoking are different
      depending on individual and environmental factors. Environmental tobacco smoke
      (ETS) is one of the most important indoor air pollutants and can interact with
      other air pollutants in eliciting respiratory outcomes during childhood. The
      increased risk of respiratory outcomes in children exposed to prenatal and early
      postnatal passive smoke might be caused by an adverse effect on both the immune
      system and the structural and functional development of the lung; this may
      explain the subsequent increased risk of incident asthma. The magnitude of the
      exposure is quite difficult to precisely quantify because it is significantly
      influenced by the child's daily activities. Because exposure to ETS is a likely
      cause for asthma onset in childhood, there is a strong need to prevent infants
      and children from breathing air contaminated with tobacco smoke. 

PMID- 25584913
TI  - Secondhand tobacco smoke exposure in low-income children and its association with
      asthma.
AB  - Secondhand tobacco smoke (SHS) is a common indoor environmental exposure that is
      particularly prevalent in low-income families. It has been found to be associated
      with asthma in some studies; however, across all relevant studies, results have
      been conflicting. This study aimed to determine the prevalence of SHS exposure in
      the home environment in a low-income, minority population and to determine the
      association of exposure with childhood asthma, wheeze, and oral corticosteroids
      use. This retrospective study analyzed self-reported data collected as part of
      the Kansas City Safe and Healthy Homes Partnership to determine prevalence of SHS
      exposure. A logistic regression model was then used to assess the association
      between exposure and asthma, oral steroid use, and wheeze. Overall, 40% of
      children lived with at least one smoker and 15% of children lived with at least
      one smoker who smoked inside the house. No significant association was found
      between asthma or oral corticosteroid use and SHS exposure. Children who lived
      with a smoker had a 1.54 increased odds of wheeze in the past year. A large
      percentage of low-income children in the Kansas City area continue to suffer the
      adverse effects of SHS. These data support the need for innovative public policy
      to protect children from such exposure in their home environment. 

PMID- 25584916
TI  - Evaluation of angiopoietin 1 and 2, vascular endothelial growth factor, and tumor
      necrosis factor alpha levels in asthmatic children.
AB  - Asthma is characterized by chronic airway inflammation that is associated with
      structural changes termed airway remodeling. Recently, cytokines/mediators that
      augment inflammation have been attracting attention in this field. The aim of
      this study was to evaluate serum angiopoietin (Ang)-1, Ang-2, vascular
      endothelial growth factor (VEGF), and tumor necrosis factor (TNF) alpha values,
      which have important roles in inflammation, angiogenesis, and remodeling in
      asthmatic children. We also documented correlations between demographic features,
      duration of asthma, and pulmonary function test (PFT) parameters. Randomly
      selected 40 children (20 male and 20 female children, aged 6-16 years) with mild
      or moderate persistent asthma and 32 healthy children (15 male and 17 female
      children, aged 6-16 years) enrolled in the study. All asthmatic children had been
      using inhaled corticosteroids at least for the last 3 months. Serum Ang-1 levels
      were significantly lower in asthmatic children than those in normal controls. The
      Ang-1/Ang-2 ratio was also significantly lower in asthmatic children compared
      with those in normal controls (p < 0.01). However, serum Ang-2, VEGF, and TNF
      alpha levels were similar in the two groups. A significant positive correlation
      was found between VEGF and duration of asthma. No correlation between serum Ang
      1, Ang-2, VEGF values, and PFT parameters was obtained. On the other hand,
      significant negative correlation was detected between serum TNF-alpha and forced
      expiratory volume in 1 second. We have shown that serum Ang-1 levels and Ang
      1/Ang-2 ratio were significantly reduced and balance was toward Ang-2 in
      asthmatics children. This process may lead to inflammation, destabilization of
      blood vessels, and trigger remodeling. 

PMID- 25584915
TI  - The associations of triclosan and paraben exposure with allergen sensitization
      and wheeze in children.
AB  - Triclosan and parabens are chemicals used in personal care and medical products
      as microbicides and preservatives. Triclosan and paraben exposure may be
      associated with allergy (atopy), but these associations have not been evaluated
      with respect to other atopic states such as eczema (atopic dermatitis). This
      study examines the associations of urinary triclosan and paraben concentrations
      with allergic sensitization and asthma in children according to eczema history.
      We performed a cross-sectional analysis of U.S. children aged 6-18 years who
      participated in the National Health and Nutrition Examination Survey (2005-2006).
      Triclosan and paraben concentrations were measured in urine. We assessed
      associations of triclosan and parabens with allergic sensitization and asthma
      using multivariable logistic regression in 837 children with complete data and
      stratified our results by eczema status. After covariate adjustment, triclosan
      and methyl and propyl paraben concentrations were positively associated with the
      odds of aeroallergen sensitization. Eczema did not significantly modify the
      association between triclosan or paraben levels and aeroallergen sensitization,
      asthma, or wheeze. The odds of parent-reported atopic asthma increased 34% (95%
      CI, 0, 81) across triclosan concentration quartiles. Increasing triclosan
      concentrations (quartiles) were associated with 2.3 times the odds of food
      sensitization (95% CI, 1.14, 4.44) among children with eczema, but not among
      children without eczema (OR, 1.25; 95% CI 0.93, 1.68; effect measure
      modification, p = 0.04). Triclosan and paraben exposures may increase the risk of
      atopic asthma and aeroallergen sensitization. Prospective studies are necessary
      to confirm these findings and determine if these chemicals pose a risk to
      children's health. 

PMID- 25584914
TI  - Homes of low-income minority families with asthmatic children have increased
      condition issues.
AB  - The home is increasingly associated with asthma. It acts both as a reservoir of
      asthma triggers and as a refuge from seasonal outdoor allergen exposure.
      Racial/ethnic minority families with low incomes tend to reside in neighborhoods
      with low housing quality. These families also have higher rates of asthma. This
      study explores the hypothesis that black and Latino urban households with
      asthmatic children experienced more home mechanical, structural condition-related
      areas of concern than white households with asthmatic children. Participant
      families (n = 140) took part in the Kansas City Safe and Healthy Homes Program,
      had at least one asthmatic child, and met income qualifications of no more than
      80% of local median income; many were below 50%. Families self-identified their
      race. Homes were assessed by environmental health professionals using a standard
      set of criteria and a specific set of on-site and laboratory sampling and
      analyses. Homes were given a score for areas of concern between 0 (best) and 53
      (worst). The study population self-identified as black (46%), non-Latino white
      (26%), Latino (14.3%), and other (12.9%). Mean number of areas of concern were
      18.7 in Latino homes, 17.8 in black homes, 13.3 in other homes, and 13.2 in white
      homes. Latino and black homes had significantly more areas of concern. White
      families were also more likely to be in the upper portion of the income. In this
      set of 140 low-income homes with an asthmatic child, households of minority
      individuals had more areas of condition concerns and generally lower income than
      other families. 

PMID- 25584918
TI  - A 68-year old woman with asymptomatic hypereosinophilia.
AB  - Eosinophilia is known to have a wide variety of etiologies including atopic
      diseases, infections, endocrine abnormalities, hematologic/neoplastic causes, and
      certain immunodeficiency disorders. In contrast, hypereosinophilic syndromes
      refer to a group of heterogeneous disorders with persistent eosinophilia and
      organ involvement. The treatment of eosinophilia varies widely based on its
      etiology and therefore should be evaluated thoroughly at onset. We present the
      case of a 68-year-old woman with isolated asymptomatic hypereosinophilia. 

PMID- 25584917
TI  - Prevalence and characteristics of reported penicillin allergy in an urban
      outpatient adult population.
AB  - Penicillin allergy remains the most common drug allergy, with a reported
      prevalence of 10% in the United States. Epidemiology of penicillin allergy in
      outpatient populations is relatively scarce. This study sought to determine the
      prevalence and characteristics of reported penicillin allergy in an urban
      outpatient population and to identify trends in clinical evaluation and
      management from a tertiary center serving a large inner-city population. A
      retrospective review of electronic medical records was performed of adult
      patients seen in the Internal Medicine Associates Clinic of Mount Sinai Hospital
      between January 31, 2012, and July 31, 2012. Medical records were selected based
      on the documentation of penicillin in patient's allergy section. Of the 11,761
      patients seen in the clinic, 1348 patients (11.5%) reported a history of
      penicillin allergy. The most common allergic reactions were rash (37%),
      unknown/undocumented (20.2%), hives (18.9%), swelling/angioedema (11.8%), and
      anaphylaxis (6.8%). There was an increased prevalence of penicillin allergy in
      female patients compared with male patients (odds ratio [OR] = 1.82; 95% CI =
      1.60, 2.08; p < 0.0001), and there were significantly fewer Asians with
      penicillin allergy compared with Caucasians (OR = 0.51; 95% CI = 0.32, 0.83; p =
      0.007). However, only 78 (6%) of the patients reporting penicillin allergy had a
      referral to an allergy specialist. Overall, improved referral to an allergist
      will help to identify patients who have penicillin allergy requiring avoidance. 

PMID- 25584919
TI  - For the patient. Secondhand tobacco smoke exposure in low-income children and its
      association with asthma.

PMID- 25584920
TI  - Optical properties and electronic transitions of DNA oligonucleotides as a
      function of composition and stacking sequence.
AB  - The role of base pair composition and stacking sequence in the optical properties
      and electronic transitions of DNA is of fundamental interest. We present and
      compare the optical properties of DNA oligonucleotides (AT)10, (AT)5(GC)5, and
      (AT-GC)5 using both ab initio methods and UV-vis molar absorbance measurements.
      Our data indicate a strong dependence of both the position and intensity of UV
      absorbance features on oligonucleotide composition and stacking sequence. The
      partial densities of states for each oligonucleotide indicate that the valence
      band edge arises from a feature associated with the PO4(3-) complex anion, and
      the conduction band edge arises from anti-bonding states in DNA base pairs. The
      results show a strong correspondence between the ab initio and experimentally
      determined optical properties. These results highlight the benefit of full
      spectral analysis of DNA, as opposed to reductive methods that consider only the
      260 nm absorbance (A260) or simple purity ratios, such as A260/A230 or A260/A280,
      and suggest that the slope of the absorption edge onset may provide a useful
      metric for the degree of base pair stacking in DNA. These insights may prove
      useful for applications in biology, bioelectronics, and mesoscale self-assembly. 

PMID- 25584921
TI  - A novel enantioselective synthesis of 6H-dibenzopyran derivatives by combined
      palladium/norbornene and cinchona alkaloid catalysis.
AB  - Organometallic and organo-catalysts are cooperatively at work in the
      enantioselective synthesis of dibenzopyran derivatives; palladium/norbornene and
      a cinchona alkaloid base guarantee good yields and satisfactory
      enantioselectivities in a one-pot reaction. 

PMID- 25584922
TI  - Effect of Left-Hand Peg Placement Direction on the Grooved Pegboard Test.
AB  - Clinical experience has shown that examinees performing the Grooved Pegboard Test
      frequently have difficulty maintaining the manualized right-to-left placement
      direction with their left hand. To date, no empirical study has examined this
      phenomenon. The purpose of this study was to investigate whether left-hand peg
      placement direction (right-to-left vs. left-to-right) influences performance on
      this standardized test of fine motor speed and dexterity. The participants were
      66 male and female student volunteers aged 18 to 58 years old. None of the
      participants had a history of neurologic disease/trauma or conditions that would
      affect motor functioning of the right and left upper extremities. Data were
      analyzed using a two-way mixed-design analysis of covariance. Results revealed a
      significant main effect for gender, F(1, 62) = 5.638, p = .021. Of primary
      interest was the main effect for placement direction, which was not significant,
      F(1, 62) = 0.108, p = .744. No significant interaction was observed, F(1, 62) =
      0.002, p = .964.

PMID- 25584923
TI  - Evaluation of oxidative DNA damage and antioxidant defense in patients with nasal
      polyps.
AB  - OBJECTIVES: The presence of inflammatory cells indicates the development of
      epithelial cell injury in nasal polyposis (NP) and the potential for production
      of high levels of reactive oxygen and nitrogen species. The aim of our study was
      to clarify the role of oxidative stress and antioxidant status in the
      deterioration accompanying NP. METHODS: Twenty patients (11 men) aged 47.2 +/-
      17.0 years with nasal polyps were included in the study. Twenty healthy subjects
      (7 men) aged 48.2 +/- 15.3 years formed the control group. The erythrocyte
      activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GPx), and plasma nitric oxide (NO) concentrations were
      measured. An alkaline comet assay was used to determine the extent of blood
      lymphocyte DNA damage of oxidized purines as glicosylo-formamidoglicosylase (Fpg)
      sites, and oxidized pyrimidines as endonuclease III (Nth) sites. RESULTS: A
      significant increase of NO (P < 0.05) and non-significant decreases of SOD (P >
      0.05), CAT (P > 0.05), and GPx (P > 0.05) were seen in NP patients compared to
      healthy controls. The level of blood lymphocyte oxidative DNA damage in NP
      patients was significantly higher compared to the control group (P = 0.01).
      DISCUSSION: The blood lymphocyte DNA damage level increased in patients with NP.
      Elevated DNA damage may be related to overproduction of reactive oxygen and
      nitrogen species and/or decreased antioxidant protection.

PMID- 25584924
TI  - Aged red garlic extract suppresses nitric oxide production in lipopolysaccharide
      treated RAW 264.7 macrophages through inhibition of NF-kappaB.
AB  - Lipopolysaccharides (LPS) activate nuclear factor kappa B (NF-kappaB), a
      transcription factor that is involved in inflammatory response. The pathways that
      activate NF-kappaB can be modulated by phytochemicals derived from garlic. We
      recently demonstrated that aged red garlic extract (ARGE), a new formulation of
      garlic, decreases nitric oxide (NO) generation by upregulating of heme oxygenase
      1 (HO-1) in RAW 264.7 cells activated by LPS. However, the effects of ARGE on LPS
      induced NF-kappaB activation are unknown. This study was performed to evaluate
      whether ARGE regulates LPS-induced NO production by modulation of NF-kappaB
      activation in macrophages. The inhibition of NF-kappaB by Bay 11-7085, an
      inhibitor of NF-kappaB, decreased LPS-induced NO production. ARGE treatment
      markedly reduced LPS-induced NO production and NF-kappaB nuclear translocation.
      ARGE downregulated expression of inducible nitric oxide synthase (iNOS) and
      upregulated expression of HO-1, a cytoprotective and anti-inflammatory protein.
      However, Bay 11-7085 only reduced iNOS expression. The NO production and iNOS
      expressions upregulated by suppression of HO-1 were suppressed by treatment with
      ARGE and Bay 11-7085. These results show that ARGE reduces LPS-induced NO
      production in macrophages through inhibition of NF-kappaB nuclear translocation
      and HO-1 activation. Compared to Bay 11-7085, ARGE may enhance anti-inflammatory
      effects by controlling other anti-inflammatory signals as well as regulation of
      NF-kappaB. 

PMID- 25584927
TI  - Role of the underlying thyroid disease on the phenotype of Graves' orbitopathy in
      a tertiary referral center.
AB  - BACKGROUND: Clinically overt Graves' orbitopathy (GO) is associated with Graves'
      disease (GD) in approximately 95% of cases, whereas the remaining 5% is observed
      in patients with hypothyroid autoimmune thyroiditis (AT) or without overt thyroid
      dysfunction (euthyroid GO). However, it is not known whether there is a
      difference in terms of GO phenotype between patients with GD and those with
      hypothyroid AT or without thyroid dysfunction, and hence this is investigated
      here. METHODS: The study design was to evaluate retrospectively all consecutive
      patients with a recent manifestation of GO, seen at their first visit to a
      tertiary referral center over a period of 10 years. In total, 358 GO patients
      were studied, and all of them underwent GO assessment. RESULTS: Of the 358
      patients studied, 341 had hyperthyroid GD, 10 had AT with hypothyroidism, and
      seven had euthyroid GO. Age, sex, and smoking habits were similar in the three
      groups, as was the time since GO was first noticed (GO duration). The vast
      majority of patients had moderate to severe, active GO, as expected in a tertiary
      referral center. Exophthalmometry, eyelid width, clinical activity score (CAS),
      diplopia, and visual acuity did not differ between patients with GD and those
      with AT or euthyroid GO, suggesting that the GO phenotype was similar.
      Accordingly, the NOSPECS score did not differ between the three groups.
      CONCLUSIONS: The phenotype of GO is similar regardless of the underlying thyroid
      disease. Because this study was performed in a tertiary referral center, this
      conclusion can be restricted only to patients who develop moderate to severe GO.

PMID- 25584926
TI  - Enhancing reactivity for bioorthogonal pretargeting by unmasking antibody
      conjugated trans-cyclooctenes.
AB  - The bioorthogonal cycloaddition reaction between tetrazine and trans-cyclooctene
      (TCO) is rapidly growing in use for molecular imaging and cell-based diagnostics.
      We have surprisingly uncovered that the majority of TCOs conjugated to monoclonal
      antibodies using standard amine-coupling procedures are nonreactive. We show that
      antibody-bound TCOs are not inactivated by trans-cis isomerization and that the
      bulky cycloaddition reaction is not sterically hindered. Instead, TCOs are likely
      masked by hydrophobic interactions with the antibody. We show that introducing
      TCO via hydrophilic poly(ethylene glycol) (PEG) linkers can fully preserve
      reactivity, resulting in >5-fold enhancement in functional density without
      affecting antibody binding. This is accomplished using a novel dual bioorthogonal
      approach in which heterobifunctional dibenzylcyclooctyne (DBCO)-PEG-TCO molecules
      are reacted with azido-antibodies. Improved imaging capabilities are demonstrated
      for different cancer biomarkers using tetrazine-modified fluorophore and quantum
      dot probes. We believe that the PEG linkers prevent TCOs from burying within the
      antibody during conjugation, which could be relevant to other bioorthogonal tags
      and biomolecules. We expect the improved TCO reactivity obtained using the
      reported methods will significantly advance bioorthogonal pretargeting
      applications. 

PMID- 25584925
TI  - A genome-wide association study of chronic obstructive pulmonary disease in
      Hispanics.
AB  - RATIONALE: Genome-wide association studies (GWAS) of chronic obstructive
      pulmonary disease (COPD) have identified disease-susceptibility loci, mostly in
      subjects of European descent. OBJECTIVES: We hypothesized that by studying
      Hispanic populations we would be able to identify unique loci that contribute to
      COPD pathogenesis in Hispanics but remain undetected in GWAS of non-Hispanic
      populations. METHODS: We conducted a metaanalysis of two GWAS of COPD in
      independent cohorts of Hispanics in Costa Rica and the United States (Multi
      Ethnic Study of Atherosclerosis [MESA]). We performed a replication study of the
      top single-nucleotide polymorphisms in an independent Hispanic cohort in New
      Mexico (the Lovelace Smokers Cohort). We also attempted to replicate prior
      findings from genome-wide studies in non-Hispanic populations in Hispanic
      cohorts. MEASUREMENTS AND MAIN RESULTS: We found no genome-wide significant
      association with COPD in our metaanalysis of Costa Rica and MESA. After combining
      the top results from this metaanalysis with those from our replication study in
      the Lovelace Smokers Cohort, we identified two single-nucleotide polymorphisms
      approaching genome-wide significance for an association with COPD. The first
      (rs858249, combined P value = 6.1 * 10(-8)) is near the genes KLHL7 and NUPL2 on
      chromosome 7. The second (rs286499, combined P value = 8.4 * 10(-8)) is located
      in an intron of DLG2. The two most significant single-nucleotide polymorphisms in
      FAM13A from a previous genome-wide study in non-Hispanics were associated with
      COPD in Hispanics. CONCLUSIONS: We have identified two novel loci (in or near the
      genes KLHL7/NUPL2 and DLG2) that may play a role in COPD pathogenesis in Hispanic
      populations.

PMID- 25584928
TI  - Head Trauma with or without Mild Brain Injury Increases the Risk of Future
      Traumatic Death: A Controlled Prospective 15-Year Follow-Up Study.
AB  - Patients who have recovered from traumatic brain injury (TBI) show an increased
      risk of premature death. To investigate long-term mortality rates in a population
      admitted to the hospital for head injury (HI), we conducted a population-based
      prospective case-control, record-linkage study, All subjects who were living in
      Northern Ostrobothnia, and who were admitted to Oulu University Hospital in 1999
      because of HI (n=737), and 2196 controls matched by age, gender, and residence
      randomly drawn from the population of Northern Ostrobothnia were included. Death
      rate and causes of death in HI subjects during 15 years of follow-up was compared
      with the general population controls. The crude mortality rates were 56.9, 18.6,
      and 23.8% for subjects having moderate-to-severe traumatic brain injury (TBI),
      mild TBI, and head injury without TBI, respectively. The corresponding
      approximate annual mortality rates were 6.7%, 1.4%, and 1.9%. All types of index
      HI predicted a significant risk of traumatic death in the future. Subjects who
      had HI without TBI had an increased risk of both death from all causes (hazard
      ratio 2.00; 95% confidence interval 1.57-2.55) and intentional or unintentional
      traumatic death (4.01, 2.20-7.30), compared with controls. The main founding was
      that even HI without TBI carries an increased risk of future traumatic death. The
      reason for this remains unknown and further studies are needed. To prevent such
      premature deaths, post-traumatic therapy should include an interview focusing on
      lifestyle factors. 

PMID- 25584929
TI  - Age-of-asthma onset as a determinant of different asthma phenotypes in adults: a
      systematic review and meta-analysis of the literature.
AB  - Age-of-asthma onset is often used to distinguish different adult asthma
      phenotypes; however, similarities and differences between early- and late-onset
      adult asthma have not been summarized to date. Of the 2921 records found, we
      identified 12 studies comparing early- and late-onset current asthma in adults.
      Age 12 was most commonly used to delineate the two age-of-onset phenotypes.
      Adults with early-onset current asthma were more likely to be atopic and had a
      higher frequency of asthma attacks, whereas adults with late-onset disease were
      more likely to be female, smokers and had greater levels of spirometrically
      defined fixed airflow obstruction. The prevalence of severe asthma was similar in
      both groups, and, in general, there were few phenotypic differences between
      severe asthmatics regardless of age of onset. Findings for several key
      characteristics, including lung function, were inconsistent between studies.
      Overall, there appears to be distinctive phenotypic differences with age of
      asthma onset. Although early-onset adult asthma is likely more attributable to
      atopy and potentially genetic factors, late-onset adult asthma appears to be more
      related to environmental risk factors, and so may be better targeted by
      preventive strategies. More detailed research is required to better characterize
      these phenotypes and to clarify potential clinical implications. 

PMID- 25584930
TI  - Educational storylines in entertainment television: audience reactions toward
      persuasive strategies in medical dramas.
AB  - Medical television drama series provide an important source of health
      information. This form of entertainment-education (E-E) can be used to influence
      knowledge, attitudes, and behaviors toward health-related issues. In the
      literature, E-E is generally regarded as a persuasive strategy in itself, whereas
      in an increasing number of E-E programs, several different persuasive strategies
      are used. An important question is how the audience ethically evaluates these
      strategies. The aim of the present study is to examine viewers' ethical judgments
      toward the use of three persuasive strategies in E-E: product placement, framing,
      and persuasion toward a controversial position. A survey among 525 viewers of 5
      popular medical dramas demonstrates that viewers evaluate the use of the
      currently investigated attitudinal statements about potential persuasive
      strategies in E-E as being immoral and that viewers prefer neutral storylines.
      Adopting a strategy that viewers find inappropriate may interfere with the
      intended prosocial effects of E-E. A broader understanding of the appropriate and
      inappropriate uses of persuasive strategies in E-E is indispensable for effective
      E-E productions. 

PMID- 25584932
TI  - The impact of ethnicity and cardiovascular risk on the pharmacologic management
      of osteoarthritis: a US perspective.
AB  - Many individuals with osteoarthritis (OA) also have other chronic, comorbid
      conditions, such as obesity, hypertension and diabetes, which can compound the
      risk for developing cardiovascular adverse events that have been associated with
      specific analgesics, most notably nonselective nonsteroidal anti-inflammatory
      drugs (NSAIDs) and selective cyclooxygenase-2 inhibitor NSAIDs. Pharmacotherapy
      may be further complicated by genetic factors that may influence drug metabolism
      in certain individuals. These risks may vary according to race and ethnicity.
      Black and Hispanic populations are known to have a higher prevalence of
      cardiovascular risk factors and disease, and a substantial proportion of black
      and Hispanic individuals possess genotypes of the cytochrome P450 (CYP) 2C9
      enzyme involved in the metabolism of many NSAIDs and the CYP2D6 enzyme involved
      in metabolism of the dual opioid agonist/norepinephrine-serotonin reuptake
      inhibitor tramadol. As a result, the efficacy and safety of available analgesics
      may vary between patients in different racial and ethnic groups. This review
      article focuses on racial and ethnic differences in cardiovascular risk and
      genetic factors altering drug efficacy and safety and evaluates the pharmacologic
      options that can be used for the management of OA in these populations.
      Particular emphasis is given to the place of topical NSAIDs and capsaicin in the
      management of OA patients for whom systemic exposure to available pharmacotherapy
      poses particular risk. Evidence-based guidelines in OA management, as they relate
      to appropriate patient-specific pharmacotherapy, are also examined.

PMID- 25584931
TI  - Human abuse potential of immediate-release/extended-release versus immediate
      release hydrocodone bitartrate/acetaminophen: a randomized controlled trial in
      recreational users of prescription opioids.
AB  - BACKGROUND: The abuse potential of prescription opioids is well established. This
      study compared positive, subjective drug effects of single, equal doses of
      biphasic immediate release (IR)/extended release (ER) hydrocodone bitartrate
      (HB)/acetaminophen (acetyl-p-aminophenol [APAP]) 7.5/325 mg tablets versus IR
      HB/APAP 7.5/325-mg tablets and placebo. METHODS: Healthy adult recreational users
      of prescription opioids entered this randomized, double-blind, double-dummy,
      active- and placebo-controlled, seven-way crossover study. Participants received
      single, total doses of IR/ER HB/APAP 22.5/975 mg (intact; three active tablets)
      and 45/1950 mg (intact and crushed [encapsulated]; six active tablets), IR
      HB/APAP 22.5/975 mg (intact; three active tablets) and 45/1950 mg (intact and
      crushed [encapsulated]; six active tablets), and placebo. Peak subjective effects
      (E(max)); time to peak effects (TE(max)); and area under the drug-effect curves
      for drug liking, high, and good drug effects were measured using visual analog
      scales. Median values with 95% confidence interval (CI) were compared using
      analysis of variance. RESULTS: Among completers (n = 52), IR/ER HB/APAP produced
      delayed and lower peak effects compared to equal doses of IR HB/APAP. Comparing
      intact tablets, the drug liking E(max) (median [95% CI]) was significantly lower
      for IR/ER HB/APAP 45/1950 mg (78.0 [73.0, 81.0]) than an equal dose of IR HB/APAP
      (89.5 [85.0, 93.0]; difference, -8.5 [-12.0, -6.0]; P < 0.001). Similar results
      were observed for intact IR/ER HB/APAP and IR HB/APAP 22.5/975 mg. Crushing IR/ER
      HB/APAP 45/1950 mg delayed these effects compared with an equal dose of crushed
      IR HB/APAP and intact IR/ER HB/APAP. CONCLUSION: IR/ER HB/APAP resulted in lower
      subjective positive drug effects than an equal dose of IR HB/APAP. Crushing IR/ER
      HB/APAP also delayed the onset of subjective effects compared with intact IR/ER
      HB/APAP. These findings suggest that biphasic IR/ER HB/APAP has lower abuse
      potential than IR HB/APAP in single equal doses. REGISTRATION: This Phase I
      clinical trial conducted in the USA was not registered.

PMID- 25584933
TI  - Multivitamin/multimineral supplements for cancer prevention: implications for
      primary care practice.
AB  - There is a popular belief that multivitamin and mineral (MVM) supplements can
      help prevent cancer and other chronic diseases. Studies evaluating the effects of
      MVM supplements on cancer risk have largely been observational, with considerable
      methodologic limitations, and with conflicting results. We review evidence from
      the few available randomized, controlled trials that assessed the effects of
      supplements containing individual vitamins, a combination of a few select
      vitamins, or complete MVM supplements, with a focus on the recent Physicians'
      Health Study II (PHS II). PHS II is a landmark trial that followed generally
      healthy middle-aged and older men (mean age 64 years) who were randomized to
      daily MVM supplementation for a mean duration of 11 years. Men taking MVMs
      experienced a statistically significant 8% reduction in incidence of total cancer
      (hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.86-0.998; p = 0.04).
      Men with a history of cancer derived an even greater benefit: cancer incidence
      was 27% lower with MVM supplementation versus placebo in this subgroup (HR: 0.73;
      95% CI: 0.56-0.96; p = 0.02). Positive results of PHS II contrast with randomized
      studies of individual vitamins or small combinations of vitamins, which have
      largely shown a neutral effect, and in some cases, an adverse effect, on cancer
      risk. The results of PHS II may have a considerable public health impact,
      potentially translating to prevention of approximately 68 000 cancers per year if
      all men were to use similar supplements, and to an even greater benefit with
      regard to secondary prevention of cancer.

PMID- 25584934
TI  - Erratum.

PMID- 25584935
TI  - Nanoscale imaging of freestanding nitrogen doped single layer graphene.
AB  - Graphene can be p-type or n-type doped by introduction of specific species.
      Doping can modulate the electronic properties of graphene, but opening a sizable
      well-tuned bandgap is essential for graphene-based tunable electronic devices. N
      doped graphene is widely used for device applications and is mostly achieved by
      introducing ammonia into the synthesis gas during the chemical vapor deposition
      (CVD) process. Post synthesis treatment studies to fine-tune the electron hole
      doping in graphene are limited. In this work realization of N-doping in large
      area freestanding single layer graphene (LFG) is achieved by post treatment in
      nitrogen plasma. The changes in the chemical and electronic properties of
      graphene are followed with Raman microscopy and mapped via synchrotron based
      scanning transmission X-ray microscopy (STXM) at the nanoscale. 

PMID- 25584936
TI  - A review on electrocardiographic changes in diabetic patients.
AB  - Prevalence of diabetes mellitus (DM) is progressively increasing, contributing to
      a parallel increase in cardiovascular morbidity and mortality, and more than
      doubling the incidence of sudden cardiac death (SCD). Certain
      electrocardiographic (ECG) characteristics, such as alternans of the T wave
      (TWA), heart rate variability (HRV) and dispersion of the QT interval, have been
      found to be predictive of the risk of SCD. This review focuses on ECG changes
      that could be found in diabetics and their potential implication for SCD risk. 

PMID- 25584937
TI  - Chronic hypersensitivity pneumonitis: important considerations in the work-up of
      this fibrotic lung disease.
AB  - PURPOSE OF REVIEW: Chronic hypersensitivity pneumonitis is increasingly
      recognized as an important mimic of other fibrotic lung diseases. This review
      will summarize recent data regarding the importance and difficulty of determining
      causative exposures both for accurate diagnosis and prognosis, and describe the
      expanded pathologic spectrum of the disease, the effects of fibrosis on prognosis
      and challenges in the diagnostic evaluation. RECENT FINDINGS: Several recent
      publications show the potential pathologic patterns induced by chronic
      hypersensitivity pneumonitis are broader than the classic triad of bronchiolitis,
      interstitial infiltrates and granulomas. Other pathologic patterns include
      nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing
      pneumonia, bronchiolitis and airway centric fibrosis. Detecting a causative
      antigen in fibrotic hypersensitivity pneumonitis is challenging but critically
      important both for accurate diagnosis and improved prognosis. The prognosis in
      hypersensitivity pneumonitis worsens in the presence of fibrosis, but it remains
      significantly better than idiopathic pulmonary fibrosis. SUMMARY:
      Hypersensitivity pneumonitis is increasingly recognized as an important cause of
      fibrotic interstitial lung disease. Hypersensitivity pneumonitis demonstrates a
      remarkable tendency to mimic other idiopathic interstitial pneumonias. A detailed
      exposure history remains a cornerstone of diagnosis and management.

PMID- 25584938
TI  - Medical imaging in occupational and environmental lung disease.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an up-to-date summary
      of developments in medical imaging in the diagnosis, surveillance, treatment, and
      screening of occupational and environmental lung diseases, focusing on articles
      published within the past 2 years. RECENT FINDINGS: Many new exposures resulting
      in lung disease have been described worldwide; medical imaging, particularly
      computed tomography (CT), is often pivotal in recognition and characterization of
      these new patterns of lung injury. Chest radiography remains important to
      surveillance studies tracking the long-term evolution of disease and
      effectiveness of air quality regulation. Finally, studies are proving the utility
      of screening with low-dose CT, and technical advances offer the prospect of
      further CT dose reduction with ultra-low-dose CT. SUMMARY: In understanding the
      best practices and new developments in medical imaging, the occupational and
      environmental medicine clinician can optimize diagnosis and management of related
      lung diseases.

PMID- 25584939
TI  - Respiratory disability and impairment: what is new?
AB  - PURPOSE OF REVIEW: This review summarizes recent advances concerning respiratory
      impairment and disability. RECENT FINDINGS: The traditional impairment assessment
      approach, depending heavily on clinical pulmonary function testing to estimate
      the match between the patient's sustainable oxygen consumption and the workplace
      requirements, continues to be widely used. Recent work indicates the need to
      reassess underlying concepts for several reasons: The relationship between basic
      pulmonary function tests and sustainable oxygen consumption varies among patients
      and conditions. Studies of the respiratory demands of modern workplaces need to
      be updated. The concepts are less easily applied to asthma than other disorders.
      Research studies present differing definitions of 'disability', and therefore the
      methods of relating impairment (function loss) and disability require
      reassessment. Recent advances provide improved understanding of the large
      societal and personal impacts of respiratory impairment and disability. SUMMARY:
      Clinicians, policymakers, and researchers should carefully consider how well the
      current highly specified impairment rating systems can be improved for accuracy
      and relevance to current home and work activities. In addition to measuring
      'impairment', clinicians should consider factors affecting how impairments lead
      to disability.

PMID- 25584941
TI  - The epidemiological profile of a middle-aged population with low back pain in
      southern Brazil.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To assess the prevalence and the
      general characteristics of low back pain (LBP) in a middle-aged population living
      in southern Brazil. SUMMARY OF BACKGROUND DATA: LBP is a widespread
      musculoskeletal condition. It is the main cause of disability in developed
      countries. It is necessary and relevant to study the risk factors for LBP to plan
      preventative action. A cross-sectional study of a middle-aged population in the
      South of Brazil was designed to look at the prevalence and general
      characteristics of LBP. METHODS: A cross-sectional study was developed in a city
      located in southern Brazil. Data were collected from 1005 individuals at
      randomized public locations. A protocol was designed to evaluate the general
      characteristics of the population: age, sex, level of education, socioeconomic
      status, body mass index, occupation, smoking, physical activity, anxiety, and
      depression. After the initial evaluation, the individuals were asked if they had
      had low back pain at least once in their lifetime. Those who answered "Yes"
      continued the questionnaire that evaluated pain intensity, characteristics, and
      related disability. After the entire group was analyzed (N = 1005), a separate
      study was performed on the participants younger than 40 years (N = 701). RESULTS:
      The mean age was 33.74 years (+/-14.76) and 61.6% of the participants were
      females. Seventy-two percent of the participants had had LBP at least once in
      their lives. The mean of visual analogue scale intensity of pain was 4.51 (+/
      2.27). The prevalence of female sex (P = 0.006) and anxiety (P < 0.001) was
      higher in those with LBP. In the group younger than 40 years, the prevalence of
      LBP was 69.7% and anxiety (P < 0.001) was the only factor related to LBP.
      CONCLUSION: Low back pain is a highly prevalent condition in a middle-aged
      population living in southern Brazil. Higher levels of anxiety and female sex
      were related to this condition in all groups, but when it was analyzed in the
      participants younger than 40 years, anxiety was the only significant variable
      related with LBP. LEVEL OF EVIDENCE: 3.

PMID- 25584942
TI  - Diagnostic capability of low- versus high-field magnetic resonance imaging for
      lumbar degenerative disease.
AB  - STUDY DESIGN: Cohort study. OBJECTIVE: To investigate the diagnostic capability
      of low-field magnetic resonance imaging (MRI) compared with high-field MRI for
      degenerative disease of the lumbar spine. SUMMARY OF BACKGROUND DATA: Low-field
      MRI has several advantages over high-field magnetic resonance systems (easier
      installation, lower purchase, and maintenance cost). The diagnostic capability of
      low-field MRI for degenerative disease of the lumbar spine has not been compared
      with that of high-field MRI. METHODS: Hundred patients (mean age: 56.3 yr, range:
      32-80; F:M = 59:41) with neurogenic claudication or sciatica were studied. All
      patients underwent MRI of the lumbar spine on both low-field (0.25T) and high
      field (1.5T or 3.0T) magnetic resonance systems. Intervertebral disc herniation,
      central canal, lateral recess, and exit foraminal stenosis as well as nerve root
      compression at L3-L4, L4-L5, and L5-S1 were evaluated by 2 radiologists for both
      low- and high-field systems using established reliable grading systems. RESULTS:
      There was excellent agreement between low- and high- field MRI with regard to
      grading the presence and severity of disc herniation (r = 0.92-0.94; P < 0.05),
      central canal stenosis (r = 0.89-0.91; P < 0.05), lateral recess stenosis (r =
      0.81-0.87; P < 0.05), and exit foramen stenosis (r = 0.81-0.89; P < 0.05).
      Descending or exiting nerve root compression occurred in 52% of patients at L3
      L4, L4-L5, or L5-S1 levels, with good agreement between low-field and high-field
      MRI (r = 0.71-0.76; P < 0.05) for nerve root compression. CONCLUSION: Excellent
      reliability between low- and high- field MRI was found for most features of
      lumbar disc degeneration, with good agreement for nerve root compression. 0.25T
      MRI was more susceptible to motion artifact, probably due to longer scanning
      time. LEVEL OF EVIDENCE: 3.

PMID- 25584943
TI  - Biomechanical simulation and analysis of scoliosis correction using a fusionless
      intravertebral epiphyseal device.
AB  - STUDY DESIGN: Computer simulations to analyze the biomechanics of a novel
      compression-based fusionless device (hemistaple) that does not cross the disc for
      the treatment of adolescent idiopathic scoliosis. OBJECTIVE: To biomechanically
      model, simulate, and analyze the hemistaple action using a human finite element
      model (FEM). SUMMARY OF BACKGROUND DATA: A new fusionless growth sparing
      instrumentation device (hemistaple), which locally compresses the growth plate
      without spanning the disc, was previously developed and successively tested on
      different animal models. METHODS: Patient-specific FEMs of the spine, rib cage,
      and pelvis were built using radiographs of 10 scoliotic adolescents (11.7 +/- 0.9
      yr; Cobb thoracic: 35 degrees  +/- 7 degrees , lumbar: 24 degrees  +/- 6 degrees
      ). A validated algorithm allowed simulating the growth (0.8-1.1 mm/yr/vertebra)
      and growth modulation process (Hueter-Volkmann principle) during a period of 2
      years. Four instrumentation configurations on the convex curves were individually
      simulated (Config 1: 5 thoracic vertebrae with hemistaples on superior endplates;
      Config 2: same as Config 1 with hemistaples on both endplates; Config 3: same as
      Config 1 + 4 lumbar vertebrae; Config 4: same as Config 2 + 4 lumbar vertebrae).
      RESULTS: Without hemistaples, on average the thoracic and lumbar Cobb angles,
      respectively, progressed from 35 degrees  to 56 degrees  and 24 degrees  to 30
      degrees , whereas the vertebral wedging at curve apices progressed from 5 degrees
      to 12 degrees . With the hemistaple Config 1, the Cobb angles progressed but
      were limited to 42 degrees  and 26 degrees , whereas the wedging ended at 8
      degrees . With Config 3, Cobb and wedging were kept nearly constant (38 degrees ,
      21 degrees , 7 degrees ). With hemistaples on both endplates (Config 2, Config
      4), the Cobb and wedging were all reduced (thoracic Cobb for Config 2 and 4: 24
      degrees  and 15 degrees ; lumbar Cobb: 21 degrees  and 11 degrees ; wedging: 2
      degrees  and 1 degrees ). CONCLUSION: This study suggests that the hemistaple has
      the biomechanical potential to control the scoliosis progression and highlights
      the importance of the instrumentation configuration to correct the spinal
      deformities. It biomechanically supports the new fusionless device concept as an
      alternative for the early treatment of idiopathic scoliosis. LEVEL OF EVIDENCE:
      5.

PMID- 25584944
TI  - Does heterotopic ossification affect the outcomes of cervical total disc
      replacement? A meta-analysis.
AB  - STUDY DESIGN: Meta-analysis. OBJECTIVE: The purpose of this study was to answer
      the following questions: (1) Does heterotopic ossification (HO) negatively
      influence clinical outcomes after cervical total disc replacement (CTDR)? (2)
      Should patients be classified into HO and non-HO groups? (3) Is there a more
      rational classification? SUMMARY OF BACKGROUND DATA: Heterotopic ossification has
      emerged as a common complication after CTDR and has been an important reason for
      reoperation, thus limiting the use of the surgery. However, the influence of HO
      on clinical outcomes after CTDR has not been well established. METHODS: A meta
      analysis was conducted with studies identified by searches of MEDLINE, EMBASE,
      and the Cochrane Library. We calculated the weighted mean differences of the
      visual analogue scale pain score, Neck Disability Index, and range of motion
      (ROM). Patients were classified into 2 groups under 3 classifications on the
      basis of the grade of HO. Results were pooled using a fixed effect model or a
      random effects model, according to the heterogeneity. RESULTS: There were
      significant differences in ROM under all 3 classifications. The visual analogue
      scale pain score and the Neck Disability Index between the patients with and
      without HO showed no significant difference after CTDR. Significant differences
      in visual analogue scale pain score were observed when patients were classified
      into a "high-grade HO" group (McAfee grades 3 or 4 HO) and a "low-grade HO" group
      (McAfee grade 0, 1, or 2 HO). CONCLUSIONS: The presence of HO is not associated
      with clinical outcomes after CTDR. However, the severity of HO actually impacts
      clinical outcomes in an inverse manner, which needs further investigation. It is
      inappropriate to classify patients on the basis of the presence of HO; further
      studies of the classifications (ROM-affecting HO vs. ROM-preserving HO; high
      grade HO vs. low-grade HO) and cervical stability after CTDR are needed. LEVEL OF
      EVIDENCE: 2.

PMID- 25584940
TI  - Expression and function of connexin 43 in human gingival wound healing and
      fibroblasts.
AB  - Connexins (C*s) are a family of transmembrane proteins that form hemichannels and
      gap junctions (GJs) on the cell membranes, and transfer small signaling molecules
      between the cytoplasm and extracellular space and between connecting cells,
      respectively. Among C*s, suppressing C*43 expression or function promotes skin
      wound closure and granulation tissue formation, and may alleviate scarring, but
      the mechanisms are not well understood. Oral mucosal gingiva is characterized by
      faster wound closure and scarless wound healing outcome as compared to skin
      wounds. Therefore, we hypothesized that C*43 function is down regulated during
      human gingival wound healing, which in fibroblasts promotes expression of genes
      conducive for fast and scarless wound healing. Cultured gingival fibroblasts
      expressed C*43 as their major connexin. Immunostaining of unwounded human gingiva
      showed that C*43 was abundantly present in the epithelium, and in connective
      tissue formed large C*43 plaques in fibroblasts. At the early stages of wound
      healing, C*43 was strongly down regulated in wound epithelial cells and
      fibroblasts, returning to the level of normal tissue by day 60 post-wounding.
      Blocking of C*43 function by C*43 mimetic peptide Gap27 suppressed GJ-mediated
      dye transfer, promoted migration, and caused significant changes in the
      expression of wound healing-associated genes in gingival fibroblasts. In
      particular, out of 54 genes analyzed, several MMPs and TGF-beta1, involved in
      regulation of inflammation and extracellular matrix (ECM) turnover, and VEGF-A,
      involved in angiogenesis, were significantly upregulated while pro-fibrotic ECM
      molecules, including Collagen type I, and cell contractility-related molecules
      were significantly down regulated. These responses involved MAPK, GSK3alpha/beta
      and TGF-beta signaling pathways, and AP1 and SP1 transcription factors. Thus,
      suppressed function of C*43 in fibroblasts promotes their migration, and
      regulates expression of wound healing-associated genes via AP1, SP1, MAPK,
      GSK3alpha/beta and TGF-beta signaling pathways, and may promote fast and scarless
      wound healing in human gingiva. 

PMID- 25584945
TI  - Retrospective study on effectiveness of activ L total disc replacement: clinical
      and radiographical results of 1- to 3-year follow-up.
AB  - STUDY DESIGN: Retrospective case series study. OBJECTIVE: To assess the
      effectiveness of activ L total disc replacement (TDR) on degenerative disc
      diseases with the clinical and radiographical results. SUMMARY OF BACKGROUND
      DATA: There are few reports on activ L TDR. This is the first one from China.
      METHODS: From March 2009 to March 2012, 32 patients with degenerative disc
      diseases underwent mono- or bisegmental lumbar TDR. Mean age was 45.1 years (32
      58 yr). Clinical outcomes were measured by Oswestry Disability Index and Visual
      analogue scale pre- and postoperatively (1, 2, and 3 yr). Radiographical
      parameters as range of motion and intervertebral disc height of the index- and
      adjacent segments were also measured. Prosthesis subsidence and heterotopic
      ossification were observed during the follow-up period. Work status was also
      tracked. RESULTS: Thirty patients were available for a mean follow-up of 28.8
      months and had complete radiographical data. At the final follow-up, the success
      rate was 86.7%. Visual analogue scale score for low back pain and leg pain, and
      Oswestry Disability Index scores significantly improved after surgery. Average
      intervertebral disc heights of patients with more than 3 years' follow-up at the
      index segment and upper and lower adjacent segments were 12.87 mm, 12.61 mm, and
      11.62 mm, respectively, showing no significant difference compared with
      preoperative scores. The range of motion of the index and upper adjacent segments
      showed a significant increase for patients with more than 3 years' follow-up.
      Changes of range of motion at lower adjacent segment were not significant. We
      observed tears of the iliac vein in 2 patients, prosthesis subsidence in 3
      patients, and heterotopic ossification in 1 patient. At the final follow-up, 18
      patients went back to their original work, 8 patients changed jobs, and 4
      patients stopped working. CONCLUSION: The 1- to 3-year follow-up of this cohort
      of patients showed satisfactory clinical outcomes. The long-term results of activ
      L TDR need more investigation. LEVEL OF EVIDENCE: 2.

PMID- 25584946
TI  - Diffusion tensor imaging in cervical syringomyelia secondary to Chiari I
      malformation: preliminary results.
AB  - STUDY DESIGN: A prospective observational analysis. OBJECTIVE: The aim was to
      perform a quantitative analysis of the neuronal status in cervical syringomyelia
      secondary to Chiari I malformation (CMI-S) using diffusion tensor imaging.
      SUMMARY OF BACKGROUND DATA: Syringomyelia is a common finding in patients with
      CMI. Conventional imaging techniques frequently fail to assist clinicians in
      quantitatively assessing the neural damage in these patients. METHODS: Twenty
      three patients with CMI-S (aged 8-25 yr) were prospectively enrolled from April
      2012 to August 2013. Sensitivity encoding single-shot echo-planar imaging was
      used for the sagittal diffusion tensor imaging. Fractional anisotropy (FA) values
      in the spinal cord were compared between the patients and normal volunteers and
      further evaluated with respect to syrinx severity and neurological
      signs/symptoms. RESULTS: Compared with the normal controls, the FA values were
      significantly decreased at the level of the syrinx (0.429 +/- 0.015 vs. 0.533 +/-
      0.007; P < 0.001), whereas no significant decreased FA value was measured in the
      tissue rostral and caudal to the syrinx. Concerning patients with different size
      of the syrinx, significantly decreased FA values at the syrinx level were
      observed in patients with a distended syrinx in comparison with those with a
      nondistended syrinx (0.397 +/- 0.013 vs. 0.480 +/- 0.018; P < 0.001). Moreover,
      the FA value at the syrinx level was found to be significantly decreased in the
      symptomatic group when compared with the nonsymptomatic or control groups (P <
      0.05), and there was also a significant difference between the 2 latter groups (P
      < 0.05). CONCLUSION: Decreased FA value at the syrinx levels may provide evidence
      of increased microstructural damage within the spinal cord parenchyma at this
      area, and changes in this diffusion tensor imaging parameter are significantly
      related to syrinx size and to the appearance of neurological signs/symptoms.
      LEVEL OF EVIDENCE: 4.

PMID- 25584947
TI  - A zero-profile anchored spacer in multilevel cervical anterior interbody fusion:
      biomechanical comparison to established fixation techniques.
AB  - STUDY DESIGN: In vitro biomechanical analysis of different multilevel cervical
      fixation techniques. OBJECTIVE: To compare the multilevel stability of a cervical
      anchored spacer (AS) with established fixation techniques. SUMMARY OF BACKGROUND
      DATA: To avoid plate-related complications, for example, dysphagia zero-profile
      AS has been developed. The use of these new zero-profile implants for treatment
      of cervical degenerative disc disease is widely accepted after encouraging
      biomechanical results for single-level instrumentation. However, there is only
      little knowledge about the biomechanical stability of these zero-profile devices
      in multilevel instrumentations. METHODS: Eight fresh-frozen human cadaveric
      cervical spines (C3-C7) were nondestructively tested in a biomechanical 3
      dimensional spine test setup. Segmental range of motion (ROM) under torsional
      load of 1.5 N.m was measured optoelectronically. Intact spine baseline
      measurement specimens were tested with 2- and 3-level instrumentation including
      (1) stand-alone PEEK-cage; (2) PEEK-cage plus locking plate; and (3) AS. Repeated
      measures analyses of variance were used for statistical analysis. RESULTS:
      Comparison of baseline ROM and stand-alone PEEK-cage instrumentation showed a
      significant lower segmental ROM only for 2-level instrumentations. Cage plus
      plate and AS were able to reduce segmental ROM significantly (P < 0.05) in 2- and
      3-level instrumentations. Comparing cage plus plate and AS, a significant lower
      ROM was detected for flexion/extension in 2- and 3-level instrumentation and for
      lateral bending in 2-level instrumentation using cage plus plate. CONCLUSION:
      Segmental stability decreases with the number of instrumented segments regardless
      of the used implant. Comparing the different fixation techniques biomechanically,
      the locking plate and cage construct was stiffer in all test modes than the
      anchored devices in multilevel constructs. However, it remains unclear what the
      clinical significance may be. LEVEL OF EVIDENCE: N/A.

PMID- 25584948
TI  - The effect of a 5-HT2A receptor antagonist on pain-related behavior, endogenous 5
      hydroxytryptamine production, and the expression 5-HT2A receptors in dorsal root
      ganglia in a rat lumbar disc herniation model.
AB  - STUDY DESIGN: Controlled, interventional, animal study. OBJECTIVE: To evaluate
      the effect of a 5-HT2A receptor antagonist on pain-related behavior, endogenous 5
      hydroxytryptamine (5-HT) plasma levels, and expression of 5-HT2A receptors in
      dorsal root ganglia (DRGs) in a rat lumbar disc herniation model. SUMMARY OF
      BACKGROUND DATA: Application of nucleus pulposus on the nerve root induces
      immediate peripheral 5-HT production and the expression of 5-HT2A receptors in
      the adjacent DRG. However, the efficacy of a 5-HT2A receptor antagonist for pain
      relief in this situation and the mechanism remain unknown. METHODS: Autologous
      nucleus pulposus was applied to the left L5 nerve root of 91 adult female Sprague
      Dawley rats. The selective 5-HT2A receptor antagonist sarpogrelate hydrochloride
      (SPG; 1 mg/kg or 10 mg/kg) or vehicle was administered orally once a day from 1
      to 21 days postoperatively. Von Frey tests were used to test pain behavior before
      and after surgery. To assess the effect of SPG on endogenous 5-HT release
      surrounding the inflamed nerve root, we measured levels of 5-hydroxyindole acetic
      acid, a 5-HT metabolite, in plasma. Expression of 5-HT2A receptors in the left L5
      DRG was examined with immunoblotting. RESULTS: The higher dose (10 mg/kg) of SPG
      significantly improved the mechanical withdrawal thresholds from 5 to 21 days
      after surgery compared with vehicle treatment. 5-hydroxyindole acetic acid in
      plasma was not significantly different among any groups at any time points. Both
      doses of SPG inhibited the expression of 5-HT2A receptors after surgery compared
      with vehicle treatment. CONCLUSION: A selective 5-HT2A receptor antagonist
      attenuated pain-related behavior and suppressed 5-HT2A receptor expression in the
      DRG, but did not affect peripheral 5-HT production. Selective 5-HT2A receptor
      antagonists may attenuate sciatica by blocking and downregulating 5-HT2A
      receptors in DRGs in lumbar disc herniation. LEVEL OF EVIDENCE: NA.

PMID- 25584949
TI  - Corpectomy in destructive thoracolumbar spine disease: Cost-effectiveness of 3
      different techniques and implications for cost reduction of delivered care.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To give some insight in
      balancing cost and effectiveness of 3 different techniques of corpectomy in
      destructive thoracolumbar spine disease. SUMMARY OF BACKGROUND DATA: Although
      there are several accepted methods of surgical treatment of single-level
      corpectomy in destructive metastatic thoracolumbar spine disease, the choice
      depends on the surgeon's preference. The techniques may vary in perioperative
      morbidity and short- and long-term outcome, but no study so far has analyzed
      their cost-effectiveness. METHODS: Seventy-five consecutive patients, mean age of
      57 years (range: 39-72 yr) with single-level destructive thoracolumbar lesion
      underwent surgical treatment with 3 different techniques in 2 centers from 2009
      to 2013. The 3 groups were (1) mini open transpedicular corpectomy, (2)
      conventional open transpedicular corpectomy, and (3) the combined posterior
      anterior approach. The data were collected prospectively according to our
      protocol and subsequently analyzed. The clinical outcome was assessed comparing
      visual analogue scale score of back pain and the short form 12 (SF-12)
      questionnaire both pre- and postoperatively. The cost analysis was done
      calculating the operative time, hospital stay, and the implant cost. RESULTS: The
      mean follow-up period was 25 months (range: 24-30 mo). The clinical outcome in
      terms of visual analogue scale score of thoracolumbar pain and SF-12 physical and
      mental score improvement (P < 0.005) were comparable with all 3 techniques. The
      radiological outcome was comparable with current available data. As the intensive
      care unit stay (average: 7 d) and the hospital stay were longer (average: 15 d)
      with combined posterior-anterior approach, the total cost was maximum (average:
      ?20,952) with this group. CONCLUSION: Using the posterior approach only was the
      most cost-effective technique, but the mini open was comparable with the
      conventional open transpedicular approach. LEVEL OF EVIDENCE: 3.

PMID- 25584950
TI  - Abnormal findings on magnetic resonance images of the cervical spines in 1211
      asymptomatic subjects.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: The purpose of this study was to
      determine the prevalence and distribution of abnormal findings on cervical spine
      magnetic resonance image (MRI). SUMMARY OF BACKGROUND DATA: Neurological symptoms
      and abnormal findings on MR images are keys to diagnose the spinal diseases. To
      determine the significance of MRI abnormalities, we must take into account the
      (1) frequency and (2) spectrum of structural abnormalities, which may be
      asymptomatic. However, no large-scale study has documented abnormal findings of
      the cervical spine on MR image in asymptomatic subjects. METHODS: MR images were
      analyzed for the anteroposterior spinal cord diameter, disc bulging diameter, and
      axial cross-sectional area of the spinal cord in 1211 healthy volunteers. The age
      of healthy volunteers prospectively enrolled in this study ranged from 20 to 70
      years, with approximately 100 individuals per decade, per sex. These data were
      used to determine the spectrum and degree of disc bulging, spinal cord
      compression (SCC), and increased signal intensity changes in the spinal cord.
      RESULTS: Most subjects presented with disc bulging (87.6%), which significantly
      increased with age in terms of frequency, severity, and number of levels. Even
      most subjects in their 20s had bulging discs, with 73.3% and 78.0% of males and
      females, respectively. In contrast, few asymptomatic subjects were diagnosed with
      SCC (5.3%) or increased signal intensity (2.3%). These numbers increased with
      age, particularly after age 50 years. SCC mainly involved 1 level (58%) or 2
      levels (38%), and predominantly occurred at C5-C6 (41%) and C6-C7 (27%).
      CONCLUSION: Disc bulging was frequently observed in asymptomatic subjects, even
      including those in their 20s. The number of patients with minor disc bulging
      increased from age 20 to 50 years. In contrast, the frequency of SCC and
      increased signal intensity increased after age 50 years, and this was accompanied
      by increased severity of disc bulging. LEVEL OF EVIDENCE: 2.

PMID- 25584951
TI  - Safe and accurate midcervical pedicle screw insertion procedure with the patient
      specific screw guide template system.
AB  - STUDY DESIGN: Clinical trial for midcervical pedicle screw insertion using a
      novel patient-specific intraoperative screw guiding device. OBJECTIVE: To
      evaluate the availability of the "Screw Guide Template" (SGT) system for
      insertion of midcervical pedicle screws. SUMMARY OF BACKGROUND DATA: Despite many
      efforts for accurate midcervical pedicle screw insertion, there still remain
      unacceptable rate of screw malpositioning that might cause neurovascular
      injuries. We developed patient-specific SGT system for safe and accurate
      intraoperative screw navigation tool and have reported its availability for the
      screw insertion to C2 vertebra and thoracic spine. METHODS: Preoperatively, the
      bone image on computed tomography was analyzed and the trajectories of the screws
      were designed in 3-dimensional format. Three types of templates were created for
      each lamina: location template, drill guide template, and screw guide template.
      During the operations, after engaging the templates directly with the laminae,
      drilling, tapping, and screwing were performed with each template. We placed 80
      midcervical pedicle screws for 20 patients. The accuracy and safety of the screw
      insertion by SGT system were evaluated using postoperative computed tomographic
      scan by calculation of screw deviation from the preplanned trajectory and
      evaluation of screw breach of pedicle wall. RESULTS: All templates fitted the
      laminae and screw navigation procedures proceeded uneventfully. All screws were
      inserted accurately with the mean screw deviation from planned trajectory of 0.29
      +/- 0.31 mm and no neurovascular complication was experienced. CONCLUSION: We
      demonstrated that our SGT system could support the precise screw insertion in
      midcervical pedicle. SGT prescribes the safe screw trajectory in a 3-dimensional
      manner and the templates fit and lock directly to the target laminae, which
      prevents screwing error along with the change of spinal alignment during the
      surgery. These advantages of the SGT system guarantee the high accuracy in screw
      insertion, which allowed surgeons to insert cervical pedicle screws safely. LEVEL
      OF EVIDENCE: 3.

PMID- 25584952
TI  - Implant materials generate different peri-implant inflammatory factors: poly
      ether-ether-ketone promotes fibrosis and microtextured titanium promotes
      osteogenic factors.
AB  - STUDY DESIGN: An in vitro study examining factors produced by human mesenchymal
      stem cells on spine implant materials. OBJECTIVE: The aim of this study was to
      examine whether the inflammatory microenvironment generated by cells on titanium
      aluminum-vanadium (Ti-alloy, TiAlV) surfaces is affected by surface microtexture
      and whether it differs from that generated on poly-ether-ether-ketone (PEEK).
      SUMMARY OF BACKGROUND DATA: Histologically, implants fabricated from PEEK have a
      fibrous connective tissue surface interface whereas Ti-alloy implants demonstrate
      close approximation with surrounding bone. Ti-alloy surfaces with complex
      micron/submicron scale roughness promote osteoblastic differentiation and foster
      a specific cellular environment that favors bone formation whereas PEEK favors
      fibrous tissue formation. METHODS: Human mesenchymal stem cells were cultured on
      tissue culture polystyrene, PEEK, smooth TiAlV, or macro-/micro-/nano-textured
      rough TiAlV (mmnTiAlV) disks. Osteoblastic differentiation and secreted
      inflammatory interleukins were assessed after 7 days. Fold changes in mRNAs for
      inflammation, necrosis, DNA damage, or apoptosis with respect to tissue culture
      polystyrene were measured by low-density polymerase chain reaction array. Data
      were analyzed by analysis of variance, followed by Bonferroni's correction of
      Student's t-test. RESULTS: Cells on PEEK upregulated mRNAs for chemokine ligand
      2, interleukin (IL) 1beta, IL6, IL8, and tumor necrosis factor. Cells grown on
      the mmnTiAlV had an 8-fold reduction in mRNAs for toll-like receptor-4. Cells
      grown on mmnTiAlV had reduced levels of proinflammatory interleukins. Cells on
      PEEK had higher mRNAs for factors strongly associated with cell death/apoptosis,
      whereas cells on mmnTiAlV exhibited reduced cytokine factor levels. All results
      were significant (P < 0.05). CONCLUSION: These results suggest that fibrous
      tissue around PEEK implants may be due to several factors: reduced osteoblastic
      differentiation of progenitor cells and production of an inflammatory environment
      that favors cell death via apoptosis and necrosis. Ti alloy surfaces with complex
      macro/micro/nanoscale roughness promote osteoblastic differentiation and foster a
      specific cellular environment that favors bone formation. LEVEL OF EVIDENCE: N/A.

PMID- 25584953
TI  - Frameless stereotactic magnetic resonance imaging-guided laser interstitial
      thermal therapy to perform bilateral anterior cingulotomy for intractable pain:
      feasibility, technical aspects, and initial experience in 3 patients.
AB  - BACKGROUND: Bilateral anterior cingulotomy is well described for certain pain and
      psychiatric disorders. Typically, stereotactic frame-based radiofrequency
      ablation is used. We report the feasibility of a frameless approach using
      magnetic resonance imaging-guided laser induced thermal therapy (MRgLITT).
      OBJECTIVE: To report experience and outcomes for MRgLITT in bilateral anterior
      cingulotomy. METHODS: Three patients with chronic refractory cancer-related pain
      underwent bilateral anterior cingulotomy. The Brief Pain Inventory (Short Form)
      was used for pain evaluation. Frameless stereotaxy using the Medtronic S7
      Navigation system was used for laser catheter placement. Patients were followed
      for evaluation of pain control outcomes. RESULTS: Four MRgLITT bilateral
      cingulotomy procedures were performed in 3 patients. Two patients had a single
      MRgLITT procedure while the third had repeat ablation after pain recurrence.
      First time ablation coordinates were (medians): x = 7.9 mm (range, 6.9-8.6); y =
      20.5 mm (range, 20-22); z = 6.9 mm (range, 2.9-7.0) above the lateral ventricle
      roof. Median trajectory length was 85.5 mm (range, 80-90). Median ablation volume
      was 1.5 cm3 (range, 0.6-1.2). Median ablation time was 257 seconds (range, 136
      338) per cingulum and power was 10.0 Watts (range, 10-11). Median preoperative
      pain severity (PSS) and interference scores (PIS) were 7.7 (range, 7.5-9.3) and
      9.9 (range, 9.7-10.0), respectively. Median postoperative PSS and PIS scores were
      1.6 (range, 1.0-2.8) and 2.0 (range, 0.3-2.6), respectively. CONCLUSION: MRgLITT
      cingulotomy is well tolerated for treatment of cancer pain and can be easily
      performed framelessly for appropriate candidates.

PMID- 25584954
TI  - Direct suture technique of normal gland edge on the incised dura margin to repair
      the intraoperative cerebrospinal fluid leakage from the arachnoid recess during
      transsphenoidal pituitary tumor surgery.
AB  - BACKGROUND: During transsphenoidal surgery for pituitary adenomas with large
      suprasellar extension, cerebrospinal fluid (CSF) leakage commonly develops from a
      defect at the arachnoid recess between the resected dura margin and the anterior
      edge of a normal pituitary gland (type 1 CSF leakage). OBJECTIVE: To evaluate the
      usefulness of a direct suture technique of the normal gland edge on the incised
      dural margin to repair intraoperative CSF leakage from the arachnoid recess.
      METHODS: Between November 2005 and December 2012, 861 patients with pituitary
      adenomas were operated on with transsphenoidal surgery, and intraoperative CSF
      leakage was encountered in 432 patients. Type 1 CSF leakage developed in a total
      of 122 patients, and their defects were repaired with the direct suture technique
      in 51 patients, whereas a fleece-coated fibrin glue patch alone was applied onto
      the defect in the other 71 patients. This direct suture technique required an
      additional 5 to 20 minutes in most cases. RESULTS: We experienced no case of
      postoperative CSF rhinorrhea in the 51 patients whose defects were repaired by
      the direct suture technique and only 1 case of CSF rhinorrhea in 71 patients
      whose defects were repaired with a fleece-coated fibrin glue patch alone. There
      was no statistical difference in the outcome between 2 groups. Postoperative
      lumbar CSF drainage was not performed in any case. CONCLUSION: Our 2 different
      repair techniques for arachnoid recess tears are very reliable methods for
      managing this type of CSF leakage. The direct suture technique may be more
      appropriate for type 1 CSF leakage with a wider gap and more prominent CSF
      leakage.

PMID- 25584955
TI  - Flow-diversion for ophthalmic segment aneurysms.
AB  - BACKGROUND: The use of flow-diversion to treat ophthalmic segment aneurysms (OSA)
      has not been well evaluated. OBJECTIVE: To assess the visual outcomes, the
      obliteration rate, and the need for retreatment of OSA treated by the pipeline
      embolization device (PED). METHODS: Patients who underwent treatment with PED for
      OSA from 2009 to 2014 were selected and retrospectively reviewed. Patient's age,
      sex, mode of presentation, and aneurysm size were recorded. The complication
      rates, the need for retreatment (due to recurrence of the aneurysm or worsening
      symptoms), the aneurysm occlusion rates, the evolution of visual symptoms, and
      the evolution of headache/retro-orbital pain were registered. RESULTS: Forty-one
      patients harboring 44 OSA treated by flow-diversion were identified. Females
      constituted 87.80% (37/41) of the cohort. The mean age was 59.16 +/- 12.54 years.
      At final angiographic follow-up, 77.27% (34/44) had complete occlusion, 6.81%
      (3/44) had near-complete occlusion, and 15.90% (7/44) had incomplete occlusion.
      Of the 22 symptomatic OSA, complete resolution or significant improvement was
      noted in 72.72% (16/22), while worsening of symptoms occurred in 4.54% (1/22).
      Five patients out of 22 (22.72%; 5/22) had no significant changes in their
      symptoms. The complication rate was 2.27% (1/44). The mortality rate was 0%.
      CONCLUSION: The low complication rate, the high obliteration rate, and the high
      rate of improvement in the visual symptoms make flow-diversion an appealing
      option for the treatment of OSA.

PMID- 25584957
TI  - Quantitative analysis of variable extent of anterior clinoidectomy with
      intradural and extradural approaches: 3-dimensional analysis and cadaver
      dissection.
AB  - BACKGROUND: Drilling of the anterior clinoid process (ACP) is an integral
      component of surgical approaches for central and paracentral skull base lesions.
      The technique to drill ACP has evolved from pure intradural to extradural and
      combined techniques. OBJECTIVE: To describe the computerized morphometric
      evaluation of exposure of optic nerve and internal carotid artery with proposed
      tailored intradural (IDAC) and complete extradural (EDAC) anterior clinoidectomy.
      METHODS: We describe a morphometric subdivision of ACP into 4 quadrangles and 1
      triangle on the basis of fixed bony landmarks. Computerized volumetric analysis
      with 3-dimensional laser scanning of dry-drilled bones for respective tailored
      IDAC and EDAC was performed. Both approaches were compared for the area and
      length of the optic nerve and internal carotid artery. Five cadaver heads were
      dissected on alternate sides with intradural and extradural techniques to
      evaluate exposure, surgical freedom, and angulation of approach. RESULTS:
      Complete anterior clinoidectomy provides a 2.5-times larger area and 2.7-times
      larger volume of ACP. Complete clinoidectomy deroofed the optic nerve to an equal
      extent as by proposed the partial tailored clinoidectomy approach. Tailored IDAC
      exposes only the distal dural ring, whereas complete EDAC exposes both the
      proximal and distal dural rings with complete exposure of the carotid cave.
      CONCLUSION: Quantitative comparative evaluation provides details of exposure and
      surgical ease with both techniques. We promote hybrid/EDAC technique for vascular
      pathologies because of better anatomic orientation. Extradural clinoidectomy is
      the preferred technique for midline cranial neoplasia. An awareness of different
      variations of clinoidectomy can prevent dependency on any particular approach and
      facilitate flexibility.

PMID- 25584958
TI  - Rapid resolution of brain ischemic hypoxia after cerebral revascularization in
      moyamoya disease.
AB  - BACKGROUND: In moyamoya disease (MMD), cerebral revascularization is recommended
      in patients with recurrent or progressive ischemic events and associated reduced
      cerebral perfusion reserve. Low-flow bypass with or without indirect
      revascularization is generally the standard surgical treatment. Intraoperative
      monitoring of cerebral partial pressure of oxygen (PtiO2) with polarographic
      Clark-type probes in cerebral artery bypass surgery for MMD-induced chronic
      cerebral ischemia has not yet been described. OBJECTIVE: To describe basal brain
      tissue oxygenation in MMD patients before revascularization as well as the
      immediate changes produced by the surgical procedure using intraoperative PtiO2
      monitoring. METHODS: Between October 2011 and January 2013, all patients with a
      diagnosis of MMD were intraoperatively monitored. Cerebral oxygenation status was
      analyzed based on the Ptio2/PaO2 ratio. Reference thresholds of PtiO2/PaO2 had
      been previously defined as below 0.1 for the lower reference threshold (hypoxia)
      and above 0.35 for the upper reference threshold (hyperoxia). RESULTS: Before STA
      MCA bypass, all patients presented a situation of severe tissue hypoxia confirmed
      by a PtiO2/PaO2 ratio <0.1. After bypass, all patients showed a rapid and
      sustained increase in PtiO2, which reached normal values (PtiO2/PaO2 ratio
      between 0.1 and 0.35). One patient showed an initial PtiO2 improvement followed
      by a decrease due to bypass occlusion. After repeat anastomosis, the patient's
      PtiO2 increased again and stabilized. CONCLUSION: Direct anastomosis quickly
      improves cerebral oxygenation, immediately reducing the risk of ischemic stroke
      in both pediatric and adult patients. Intraoperative PtiO2 monitoring is a very
      reliable tool to verify the effectiveness of this revascularization procedure.

PMID- 25584956
TI  - The Chiari Severity Index: a preoperative grading system for Chiari malformation
      type 1.
AB  - BACKGROUND: To develop evidence-based treatment guidelines for Chiari
      malformation type 1 (CM-1), preoperative prognostic indices capable of
      stratifying patients for comparative trials are needed. OBJECTIVE: To develop a
      preoperative Chiari Severity Index (CSI) integrating the clinical and
      neuroimaging features most predictive of long-term patient-defined improvement in
      quality of life (QOL) after CM-1 surgery. METHODS: We recorded preoperative
      clinical (eg, headaches, myelopathic symptoms) and neuroimaging (eg, syrinx size,
      tonsillar descent) characteristics. Brief follow-up surveys were administered to
      assess overall patient-defined improvement in QOL. We used sequential
      sequestration to develop clinical and neuroimaging grading systems and
      conjunctive consolidation to integrate these indices to form the CSI. We
      evaluated statistical significance using the Cochran-Armitage test and
      discrimination using the C statistic. RESULTS: Our sample included 158 patients.
      Sequential sequestration identified headache characteristics and myelopathic
      symptoms as the most impactful clinical parameters, producing a clinical grading
      system with improvement rates ranging from 81% (grade 1) to 58% (grade 3) (P =
      .01). Based on sequential sequestration, the neuroimaging grading system included
      only the presence (55% improvement) or absence (74% improvement) of a syrinx >=6
      mm (P = .049). Integrating the clinical and neuroimaging indices, improvement
      rates for the CSI ranged from 83% (grade 1) to 45% (grade 3) (P = .002). The
      combined CSI had moderately better discrimination (c = 0.66) than the clinical (c
      = 0.62) or neuroimaging (c = 0.58) systems alone. CONCLUSION: Integrating
      clinical and neuroimaging characteristics, the CSI is a novel tool that predicts
      patient-defined improvement after CM-1 surgery. The CSI may aid preoperative
      counseling and stratify patients in comparative effectiveness trials.

PMID- 25584959
TI  - Use of tissue-glue-coated collagen sponge (TachoSil) to repair minor cerebral
      dural venous sinus lacerations: technical note.
AB  - BACKGROUND: Significant hemorrhage may occur from the cerebral venous sinuses
      during the dural separation from the bone flap, particularly in elderly patients.
      It is important to achieve an urgent hemostatic control. OBJECTIVE: To evaluate
      the efficacy and safety of a new fixed combination tissue sealant (TachoSil) in
      patients with bleeding from lacerations of cerebral venous sinuses. METHODS:
      Between September 2012 and June 2014, 57 patients (39 female, 18 male) presenting
      with iatrogenic tears of the superior sagittal or transverse/sigmoid sinuses were
      treated with a topical fibrin sealant patch. Intraoperative source of bleeding,
      time to bleeding control, quantity of sealant sponge used, and postoperative
      complications were evaluated. Time to hemostasis was used as the primary end
      point. RESULTS: Effective hemostasis, defined as cessation of bleeding after
      application of topical hemostatic agent, was achieved no later than 4 minutes in
      all except 5 patients with persistent bleeding from the sinus. In these 5 cases,
      bleeding was finally stopped after application of a new larger layer of TachoSil
      Sponge (2 cases) or gelatin hemostatic matrix (2 cases) or fibrin glue (1 case)
      over the layer of TachoSil. CONCLUSION: We report our experience with a new
      hemostasis technique to manage bleeding from iatrogenic lacerations of cerebral
      venous sinuses.

PMID- 25584961
TI  - Primary epiploic appendagitis in a pediatric patient: prominent role of Magnetic
      Resonance Imaging in the diagnosis.

PMID- 25584960
TI  - Out-of-pocket expenditure on chronic non-communicable diseases in sub-Saharan
      Africa: the case of rural Malawi.
AB  - In Sub-Saharan Africa (SSA) the disease burden of chronic non-communicable
      diseases (CNCDs) is rising considerably. Given weaknesses in existing financial
      arrangements across SSA, expenditure on CNCDs is often borne directly by patients
      through out-of-pocket (OOP) payments. This study explored patterns and
      determinants of OOP expenditure on CNCDs in Malawi. We used data from the first
      round of a longitudinal household health survey conducted in 2012 on a sample of
      1199 households in three rural districts in Malawi. We used a two-part model to
      analyze determinants of OOP expenditure on CNCDs. 475 respondents reported at
      least one CNCD. More than 60% of the 298 individuals who reported seeking care
      incurred OOP expenditure. The amount of OOP expenditure on CNCDs comprised 22% of
      their monthly per capita household expenditure. The poorer the household, the
      higher proportion of their monthly per capita household expenditure was spent on
      CNCDs. Higher severity of disease was significantly associated with an increased
      likelihood of incurring OOP expenditure. Use of formal care was negatively
      associated with the possibility of incurring OOP expenditure. The following
      factors were positively associated with the amount of OOP expenditure: being
      female, Alomwe and household head, longer duration of disease, CNCDs targeted
      through active screening programs, higher socio-economic status, household head
      being literate, using formal care, and fewer household members living with a CNCD
      within a household. Our study showed that, in spite of a context where care for
      CNCDs should in principle be available free of charge at point of use, OOP
      payments impose a considerable financial burden on rural households, especially
      among the poorest. This suggests the existence of important gaps in financial
      protection in the current coverage policy. 

PMID- 25584962
TI  - Trypsin-inspired poly(urethane-urea)s based on poly-lysine oligomer segment.
AB  - A new kind of biodegradable poly(urethane-urea)s based on poly-lysine oligomer
      used as the soft segment was synthesized and characterized. In vitro degradation
      behavior of poly (urethane-urea)s was investigated, and was assessed by (1)H NMR
      and mass loss. The results indicated that the peptide bonds in poly(urethane
      urea)s were effectively cleaved in simulated pancreatic juice containing trypsin,
      while those in buffer solution without trypsin remained unaffected. The
      degradability was obviously improved by introducing poly-lysine oligomer into the
      main chain of poly(urethane-urea)s. The results of cells viability test indicated
      that the poly (urethane-urea)s showed a good biocompatibility on endothelial
      cells. The thermostability and hydrophilicity of poly(urethane-urea)s increased
      with increase in poly-lysine oligomer content. 

PMID- 25584963
TI  - A spatiotemporal characterization of the effect of p53 phosphorylation on its
      interaction with MDM2.
AB  - The interaction of p53 and MDM2 is modulated by the phosphorylation of p53. This
      mechanism is key to activating p53, yet its molecular determinants are not fully
      understood. To study the spatiotemporal characteristics of this molecular process
      we carried out Brownian dynamics simulations of the interactions of the MDM2
      protein with a p53 peptide in its wild type state and when phosphorylated at
      Thr18 (pThr18) and Ser20 (pSer20). We found that p53 phosphorylation results in
      concerted changes in the topology of the interaction landscape in the diffusively
      bound encounter complex domain. These changes hinder phosphorylated p53 peptides
      from binding to MDM2 well before reaching the binding site. The underlying
      mechanism appears to involve shift of the peptide away from the vicinity of the
      MDM2 protein, peptide reorientation, and reduction in peptide residence time
      relative to wild-type p53 peptide. pThr18 and pSr20 p53 peptides experience
      reduction in residence times by factors of 13.6 and 37.5 respectively relative to
      the wild-type p53 peptide, indicating a greater role for Ser20 phosphorylation in
      abrogating p53 MDM2 interactions. These detailed insights into the effect of
      phosphorylation on molecular interactions are not available from conventional
      experimental and theoretical approaches and open up new avenues that incorporate
      molecular interaction dynamics, for stabilizing p53 against MDM2, which is a
      major focus of anticancer drug lead development. 

PMID- 25584964
TI  - Inflammatory responses to a Clostridium perfringens type A strain and alpha-toxin
      in primary intestinal epithelial cells of chicken embryos.
AB  - The causative pathogen of necrotic enteritis is the Gram-positive bacterium
      Clostridium perfringens. Its main cell wall component, peptidoglycan (PGN), can
      be recognized by Toll-like receptor 2 and nucleotide-binding oligomerization
      domain (NOD). Consequently, the immune response is initiated via activation of
      nuclear factor kappa B (NF-kappaB) signalling pathway. An in vitro study was
      conducted to investigate chicken intestinal inflammatory responses to C.
      perfringens type A and one of its virulence factors, alpha-toxin. In primary
      intestinal epithelial cells, C. perfringens as well as commercially available PGN
      and alpha-toxin challenge upregulated mRNA expression of interleukin (IL)-6, IL-8
      and inducible nitric oxide synthase (iNOS) with a dosage-dependent manner at 3 h
      post infection (p.i.; P <= 0.001). Time-course effects of three stimulators at
      high concentration were further examined. C. perfringens infection elevated IL-6,
      IL-8 and iNOS levels from 1 h to 9 h p.i., while PGN treatment increased IL-6 and
      IL-8 expression at 1 h and 3 h p.i. (P < 0.05). Bacterial and PGN treatments
      induced NOD1 expression at 6 h p.i. and only bacterial infection boosted NF
      kappaB p65 expression at 6 h and 9 h p.i. (P < 0.05). alpha-Toxin treatment
      upregulated IL-6 and IL-8 expression throughout infection, as well as iNOS, TNF
      alpha and NF-kappaB p65 expression at later hours p.i. (P < 0.05). In conclusion,
      both C. perfringens and alpha-toxin challenge induced intense cytokine expression
      associated with NF-kappaB activation in chicken intestinal epithelial cells. The
      receptors for the recognition of PGN component of C. perfringens need further
      investigation. 

PMID- 25584968
TI  - A spray-coating process for highly conductive silver nanowire networks as the
      transparent top-electrode for small molecule organic photovoltaics.
AB  - We present a novel top-electrode spray-coating process for the solution-based
      deposition of silver nanowires (AgNWs) onto vacuum-processed small molecule
      organic electronic solar cells. The process is compatible with organic light
      emitting diodes (OLEDs) and organic light emitting thin film transistors (OLETs)
      as well. By modifying commonly synthesized AgNWs with a perfluorinated
      methacrylate, we are able to disperse these wires in a highly fluorinated
      solvent. This solvent does not dissolve most organic materials, enabling a top
      spray-coating process for sensitive small molecule and polymer-based devices. The
      optimized preparation of the novel AgNW dispersion and spray-coating at only 30 
      degrees C leads to high performance electrodes directly after the deposition,
      exhibiting a sheet resistance of 10.0 Omega ?(-1) at 87.4% transparency (80.0%
      with substrate). By spraying our novel AgNW dispersion in air onto the vacuum
      processed organic p-i-n type solar cells, we obtain working solar cells with a
      power conversion efficiency (PCE) of 1.23%, compared to the air exposed reference
      devices employing thermally evaporated thin metal layers as the top-electrode.

PMID- 25584966
TI  - Effect of glutamine dipeptide supplementation on primary outcomes for elective
      major surgery: systematic review and meta-analysis.
AB  - To evaluate if glutamine (GLN) supplementation may affect primary outcomes in
      patients undergoing major elective abdominal operations, we performed a
      systematic literature review of randomized clinical trials (RCTs) published from
      1983 to 2013 and comparing intravenous glutamine dipeptide supplementation to no
      supplementation in elective surgical abdominal procedures. A meta-analysis for
      each outcome (overall and infectious morbidity and length of stay) of interest
      was carried out. The effect size was estimated by the risk ratio (RR) or by the
      weighted mean difference (WMD). Nineteen RCTs were identified with a total of
      1243 patients (640 receiving GLN and 603 controls). In general, the studies were
      underpowered and of medium or low quality. GLN supplementation did not affect
      overall morbidity (RR = 0.84, 95% CI 0.51 to 1.36; p = 0.473) and infectious
      morbidity (RR = 0.64; 95% CI = 0.38 to 1.07; p = 0.087). Patients treated with
      glutamine had a significant reduction in length of hospital stay (WMD = -2.67;
      95% CI = -3.83 to -1.50; p < 0.0001). In conclusion, GLN supplementation appears
      to reduce hospital stay without affecting the rate of complications. The positive
      effect of GLN on time of hospitalization is difficult to interpret due to the
      lack of significant effects on surgery-related morbidity. 

PMID- 25584983
TI  - School-based program options to promote physical activity: a response.
AB  - This commentary is a response to PM-14-1065R1 and addresses issues raised
      regarding research presented in PM-14-443. 

PMID- 25584967
TI  - Fetal adrenal demedullation lowers circulating norepinephrine and attenuates
      growth restriction but not reduction of endocrine cell mass in an ovine model of
      intrauterine growth restriction.
AB  - Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and
      elevated plasma norepinephrine (NE) that become increasingly pronounced
      throughout the third trimester and contribute to intrauterine growth restriction
      (IUGR). This study evaluated the effect of fetal adrenal demedullation (AD) on
      growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR
      was created by exposing pregnant ewes to elevated ambient temperatures during mid
      gestation. Treatment groups consisted of control and IUGR fetuses with either
      surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA), a time
      point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses
      were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in
      IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham
      compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD
      fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD
      fetuses weighed more and asymmetrical organ growth was absent. Pancreatic beta
      cell mass and alpha-cell mass were lower in both IUGR-sham and IUGR-AD fetuses
      compared to controls, however, pancreatic endocrine cell mass relative to fetal
      mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently
      of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of
      growth but not pancreatic endocrine cell mass in IUGR fetuses. 

PMID- 25584984
TI  - Recent trends in adherence to continuous screening for breast cancer among
      Medicare beneficiaries.
AB  - OBJECTIVE: The aim of this study is to examine recent trends in adherence to
      continuous screening, especially the rate of subsequent screening mammography
      following an initial screening before and after the U.S. Preventive Services Task
      Force (USPSTF) revised its guidelines on breast cancer in November 2009. METHODS:
      We retrospectively analyzed Medicare fee-for-service claims data to: 1) compare
      rate of subsequent screening mammography over 27 month periods for 317,150 women
      screened in either 2004 or 2009; and 2) examine patterns of subsequent screening
      by age and race. RESULTS: When adjusted for age, race, state of residence, county
      level covariates, and clustered on ordering provider, the rate of subsequent
      screening decreased in 2009 relative to 2004 (OR=0.75; 95% CI: 0.74-0.76).
      Adjusted odds ratios are similar for alternative follow-up windows (15 months,
      0.71; 24 months, 0.70; 30 months 0.75). The decline was mostly attributable to
      women 75 and older who are now less likely to return for a subsequent screening.
      Although USPSTF guidelines call for 24 months, approximately half of women
      continue screening at 12-month intervals in both cohorts. CONCLUSIONS: The rate
      of subsequent screening mammography has declined after 2009. Older women seem to
      follow the revised USPSTF guideline, but confusion by physicians and patients
      about competing guidelines may be contributing to these findings.

PMID- 25584985
TI  - Factors influencing the disconnect between self-perceived health status and
      actual health profile: implications for improving self-awareness of health
      status.
AB  - OBJECTIVE: Self-perceived health is an often used proxy measure for disease and
      health behavior status. Due to its convenience in clinical and epidemiological
      contexts, it is of interest to examine factors that may help to explain the
      potential disconnect between perceived and actual health, which was the purpose
      of this study. METHODS: Data from the 2005-2006 NHANES were used (n=1,999
      adults). Perceived health status was self-reported, with the following 6 health
      characteristics assessed: 1) physical activity; 2) healthy eating, 3) smoking
      status; 4) sleep duration; 5) depression status; and 6) weight status. RESULTS:
      For every 5year increase in age, participants had a 7% reduced odds of having a
      discrepancy between perceived and actual health; Mexican Americans (vs. non
      Hispanic Whites) had a 49% reduced odds of discrepancy; non-Hispanic Blacks (vs.
      non-Hispanic Whites) had a 40% increased odds of discrepancy, and individuals
      with a higher SES had a 12% increased odds of discrepancy. CONCLUSION: Targeted
      public health and educational messages to young adults, non-Hispanic Blacks, and
      those with a higher SES may be needed to help prevent discrepancies between
      perceived and actual health. Preventing this disconnect may help to, for example,
      improve individual health awareness, and ultimately, improve health outcomes.

PMID- 25584965
TI  - Regulation of calcitriol biosynthesis and activity: focus on gestational vitamin
      D deficiency and adverse pregnancy outcomes.
AB  - Vitamin D has garnered a great deal of attention in recent years due to a global
      prevalence of vitamin D deficiency associated with an increased risk of a variety
      of human diseases. Specifically, hypovitaminosis D in pregnant women is highly
      common and has important implications for the mother and lifelong health of the
      child, since it has been linked to maternal and child infections, small-for
      gestational age, preterm delivery, preeclampsia, gestational diabetes, as well as
      imprinting on the infant for life chronic diseases. Therefore, factors that
      regulate vitamin D metabolism are of main importance, especially during
      pregnancy. The hormonal form and most active metabolite of vitamin D is
      calcitriol. This hormone mediates its biological effects through a specific
      nuclear receptor, which is found in many tissues including the placenta.
      Calcitriol synthesis and degradation depend on the expression and activity of
      CYP27B1 and CYP24A1 cytochromes, respectively, for which regulation is tissue
      specific. Among the factors that modify these cytochromes expression and/or
      activity are calcitriol itself, parathyroid hormone, fibroblast growth factor 23,
      cytokines, calcium and phosphate. This review provides a current overview on the
      regulation of vitamin D metabolism, focusing on vitamin D deficiency during
      gestation and its impact on pregnancy outcomes. 

PMID- 25584986
TI  - Perceptions and the role of group exercise among New York City adults, 2010-2011:
      an examination of interpersonal factors and leisure-time physical activity.
AB  - OBJECTIVE: To examine associations of descriptive norms (i.e., behaviors of
      social group members) and exercising 'with a partner' or 'as a part of a group'
      on weekly leisure-time physical activity. METHODS: T-tests and adjusted
      multivariable linear models were used to test the associations between
      descriptive norms and exercising with a partner or as a part of a group with self
      reported leisure-time physical activity using the cross-sectional, population
      based New York City Physical Activity and Transit (PAT) Survey 2010-2011
      (n=3806). RESULTS: Overall, 70.6% of adult New Yorkers reported having physically
      active friends. Having active friends was associated with increased leisure-time
      physical activity; however, the effect varied by sex. Compared to those who did
      not have active friends, males with active friends reported two times more
      activity (56 min/week) and women reported two and a half times more activity (35
      min/week) (both p-values<0.001). Physically active males and females who usually
      engaged in leisure-time activities as a part of a group reported 1.4 times more
      activity than those who exercised alone (both p-values<0.03). CONCLUSIONS:
      Descriptive norms and group exercise were associated with leisure-time physical
      activity among adults. Based on these associations, encouraging group exercise
      may be an effective strategy for increasing leisure-time physical activity among
      certain subgroups.

PMID- 25584988
TI  - Unimolecular Rate Expression for Cyclohexene Decomposition and Its Use in
      Chemical Thermometry under Shock Tube Conditions.
AB  - The methods used in deriving the rate expressions from comparative rate single
      pulse shock tube studies, recent direct shock tube studies, and high-pressure
      flow experiments bearing on the data for the reverse Diels-Alder decomposition of
      cyclohexene to form ethylene and 1,3-butadiene are reviewed. This current
      interest is due to the increasing need for accurate kinetics and physical data
      (particularly the temperature) for realistic simulations in practical areas such
      as combustion. The rate constants derived from the direct shock tube studies and
      high-pressure flow experiments are somewhat larger than those used in comparative
      rate single-pulse shock tube experiments. For the latter, it is shown that they
      have been derived from a variety of independent experiments that include rate
      constants for unimolecular decomposition and isomerization processes that are
      considered to be well understood. The possibility of non-Arrhenius behavior in
      the unimolecular rate constants as a consequence of the large range covered in
      rate constants (as much as 12 orders of magnitude) for the comparative rate
      experiments has been examined and ruled out as a source of the discrepancy. Our
      analysis shows that there is the need to consider the possibility of radical
      induced decompositions for verifying the correctness of the reaction mechanisms
      in studying unimolecular reactions. In the case of cyclohexene decomposition,
      recent experiments demonstrating the presence of residual amounts of H atoms in
      shock tube experiments suggest that addition to the double bond can also lead to
      the formation of ethylene and 1,3-butadiene and hence to rate constants larger
      than the true values. This possibility is even more likely to occur in high
      pressure flow experiments. As a result, the internal standard method must be used
      with care and a radical inhibitor should always be present in sufficiently large
      quantities to suppress possible chain reactions. The present analysis results
      have important implications for the determination of temperatures in shock tubes.

PMID- 25584987
TI  - U.S. adults and child snacking patterns among sugar-sweetened beverage drinkers
      and non-drinkers.
AB  - OBJECTIVE: To provide national estimates of snack patterns for sugar-sweetened
      beverage (SSB) drinkers and non-SSB drinkers among U.S. children and adults.
      METHODS: We analyzed 24-h dietary recall data obtained from the National Health
      and Nutrition Examination Survey 1999-2010 among children (ages 2 to 19) and
      adults (aged 20 and older) (N=46,932). RESULTS: For children and adults, SSB
      drinkers were significantly more likely than non-SSB drinkers to consume snacks
      (children: salty, 60% vs. 50%; sweet, 69% vs. 65%; adults: salty, 64% vs. 58%;
      sweet, 64% vs. 58%), calories from snacks (children: salty snacks, 258 vs. 213
      kcal; sweet snacks, 322 vs. 291 kcal; adults: salty snacks, 261 vs. 236 kcal;
      sweet snacks, 370 vs. 350 kcal), and total calories (children: 2098 vs. 1,804
      kcal; adults: 2329 vs. 2,049 kcal) (p<0.05). Among adolescents, Blacks had a
      significantly higher percentage of SSB drinkers and salty snack consumers than
      Whites and Hispanics (SSB consumers: White, 79%; Black, 86%; Hispanic, 82%; salty
      snack consumers: White, 56%; Black, 62%; Hispanic, 54%; p<0.05). All ages were
      more likely to consume sweet snacks at home (p<0.05). CONCLUSIONS: Adults and
      children who drink SSBs are more likely to snack and consume more calories from
      snacks than non-SSB drinkers, particularly Black adolescents and young adults.

PMID- 25584989
TI  - Mechanics analysis of molar tooth splitting.
AB  - A model for the splitting of teeth from wedge loading of molar cusps from a round
      indenting object is presented. The model is developed in two parts: first, a
      simple 2D fracture mechanics configuration with the wedged tooth simulated by a
      compact tension specimen; second, a full 3D numerical analysis using extended
      finite element modeling (XFEM) with an embedded crack. The result is an explicit
      equation for splitting load in terms of indenter radius and key tooth dimensions.
      Fracture experiments on extracted human molars loaded axially with metal spheres
      are used to quantify the splitting forces and thence to validate the model. The
      XFEM calculations enable the complex crack propagation, initially in the enamel
      coat and subsequently in the interior dentin, to be followed incrementally with
      increasing load. The fracture evolution is shown to be stable prior to failure,
      so that dentin toughness, not strength, is the controlling material parameter.
      Critical conditions under which tooth splitting in biological and dental settings
      are likely to be met, however rare, are considered. 

PMID- 25584991
TI  - Electrogenerated chemiluminescence from heteroleptic iridium(III) complexes with
      multicolor emission.
AB  - Electrogenerated chemiluminescence (ECL) with different emission colors is
      important in the development of multichannel analytical techniques. In this
      report, five new heteroleptic iridium(III) complexes were synthesized, and their
      photophysical, electrochemical, and ECL properties were studied. Here, 2-(2,4
      difluorophenyl)pyridine (dfppy, complex 1), 2-phenylbenzo[d]thiazole (bt, complex
      2), and 2-phenylpyridine (ppy, complex 3) were used as the main ligands to tune
      the emission color, while avobenzone (avo) was used as the ancillary ligand. For
      comparison, complexes 4 and 5 with 2-phenylpyridine and 2-phenylbenzo[d]thiazole
      as the main ligand, respectively, and acetyl acetone (acac) as the ancillary
      ligand were also synthesized. All five iridium(III) complexes had strong
      intraligand absorption bands (pi-pi*) in the UV region (below 350 nm) and a
      featureless MLCT (d-pi*) transition in the visible 400-500 nm range. Multicolored
      emissions were observed for these five iridium(III) complexes, including green,
      orange, and red for complexes 4, 5, 2, 1, 3, respectively. Density functional
      theory calculations indicate that the electronic density of the highest occupied
      molecular orbital is entirely located on the C^N ligands and the iridium atom,
      while the formation of the lowest unoccupied molecular orbital (LUMO) is
      complicated. The LUMO is mainly assigned to the ancillary ligand for complexes 1
      and 3 but to the C^N ligand for complexes 2, 4, and 5. Cyclic voltammetry studies
      showed that all these complexes have a reversible oxidation wave, but no
      reduction waves were found in the electrochemical windows of CH2Cl2. The E1/2(ox)
      values of these complexes ranged from 0.642 to 0.978 V for complexes 3, 4, 2, 5,
      1, (in increasing order) and are all lower than that of Ru(bpy)3(2+). Most
      importantly, when using tripropylamine as a coreactant, complexes 1-5 exhibited
      intense ECL signals with an emission wavelength centered at 616, 580, 663, 536,
      and 569 nm, respectively. In addition, complexes 1, 2, and 5 displayed
      approximately 2, 11, and 214 times higher ECL efficiencies than Ru(bpy)3(2+)
      under identical conditions.

PMID- 25584990
TI  - Collagen-gelatin mixtures as wound model, and substrates for VEGF-mimetic peptide
      binding and endothelial cell activation.
AB  - In humans, high level of collagen remodeling is seen during normal physiological
      events such as bone renewal, as well as in pathological conditions, such as
      arthritis, tumor growth and other chronic wounds. Our lab recently discovered
      that collagen mimetic peptide (CMP) is able to hybridize with denatured collagens
      at these collagen remodeling sites with high affinity. Here, we show that the
      CMP's high binding affinity to denatured collagens can be utilized to deliver
      angiogenic signals to scaffolds composed of heat-denatured collagens (gelatins).
      We first demonstrate hybridization between denatured collagens and QKCMP, a CMP
      with pro-angiogenic QK domain. We show that high levels of QKCMP can be
      immobilized to a new artificial matrix containing both fibrous type I collagen
      and heat denatured collagen through triple helix hybridization, and that the
      QKCMP is able to stimulate early angiogenic response of endothelial cells (ECs).
      We also show that the QKCMP can bind to excised tissues from burn injuries in
      cutaneous mouse model, suggesting its potential for promoting neovascularization
      of burn wounds. 

PMID- 25584992
TI  - Electrospun microfiber membranes embedded with drug-loaded clay nanotubes for
      sustained antimicrobial protection.
AB  - Guided tissue regeneration/guided bone regeneration membranes with sustained drug
      delivery were developed by electrospinning drug-loaded halloysite clay nanotubes
      doped into poly(caprolactone)/gelatin microfibers. Use of 20 wt % nanotube
      content in fiber membranes allowed for 25 wt % metronidazole drug loading in the
      membrane. Nanotubes with a diameter of 50 nm and a length of 600 nm were aligned
      within the 400 nm diameter electrospun fibers, resulting in membranes with
      doubling of tensile strength along the collector rotating direction. The
      halloysite-doped membranes acted as barriers against cell ingrows and have good
      biocompatibility. The metronidazole-loaded halloysite nanotubes incorporated in
      the microfibers allowed for extended release of the drugs over 20 days, compared
      to 4 days when directly admixed into the microfibers. The sustained release of
      metronidazole from the membranes prevented the colonization of anaerobic
      Fusobacteria, while eukaryotic cells could still adhere to and proliferate on the
      drug-loaded composite membranes. This indicates the potential of halloysite clay
      nanotubes as drug containers that can be incorporated into electrospun membranes
      for clinical applications. 

PMID- 25584993
TI  - Investigating albendazole desmotropes by solid-state NMR spectroscopy.
AB  - Characterization of the molecular structure and physicochemical solid-state
      properties of the solid forms of pharmaceutical compounds is a key requirement
      for successful commercialization as potential active ingredients in drug
      products. These properties can ultimately have a critical effect on the
      solubility and bioavailability of the final drug product. Here, the desmotropy of
      Albendazole forms I and II was investigated at the atomic level. Ultrafast magic
      angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) spectroscopy,
      together with powder X-ray diffraction, thermal analysis, and Fourier transform
      infrared spectroscopy, were performed on polycrystalline samples of the two
      solids in order to fully characterize and distinguish the two forms. High
      resolution one-dimensional (1)H, (13)C, and (15)N together with two-dimensional
      (1)H/(1)H single quantum-single quantum, (1)H/(1)H single quantum-double quantum,
      and (1)H/(13)C chemical shift correlation solid-state NMR experiments under MAS
      conditions were extensively used to decipher the intramolecular and
      intermolecular hydrogen bonding interactions present in both solid forms. These
      experiments enabled the unequivocal identification of the tautomers of each
      desmotrope. Our results also revealed that both solid forms may be described as
      dimeric structures, with different intermolecular hydrogen bonds connecting the
      tautomers in each dimer. 

PMID- 25584995
TI  - Randomized Crossover Trial of Single Use Hydrophilic Coated vs Multiple Use
      Polyvinylchloride Catheters for Intermittent Catheterization to Determine
      Incidence of Urinary Infection.
AB  - PURPOSE: Urinary tract infection is a key issue for long-term intermittent
      catheterization users. Various catheter designs and methods have evolved to
      decrease the risk but the evidence remains unclear regarding whether product type
      improves outcomes. We determined whether single use hydrophilic coated catheters
      reduced urinary tract infections compared to multiple use polyvinylchloride
      catheters for children with neurogenic bladder due to spina bifida. MATERIALS AND
      METHODS: This was a randomized crossover 4-center trial with 2 treatment periods
      of 24 weeks each, consisting of single use hydrophilic coated catheter and
      multiple use polyvinylchloride catheter (washed with soap and water, and air
      dried after each use). Each week participants recorded symptoms and urine results
      (Multistix(r) 8SG reagent strip). Primary outcome was person-weeks of urinary
      tract infection, defined as positive leukocytes plus fever, flank pain, increased
      incontinence, malaise, or cloudy or odorous urine requiring antibiotic treatment.
      Individuals were included if they were a child or young adult with spina bifida
      and used intermittent catheterization as the primary method of bladder emptying.
      RESULTS: Calculated sample size was 97. More than 120 patients were screened, of
      whom 66 were randomized and 45 completed both trial arms. Mean age was 10.6
      years. Of the patients 21 were male and 24 were female. Mean +/- SD person-weeks
      of urinary tract infection was 3.42 +/- 4.67 in the single use hydrophilic coated
      catheter group and 2.20 +/- 3.23 in the multiple use polyvinylchloride catheter
      group (p <0.001). There were no statistical differences in weeks of febrile
      urinary tract infection or antibiotic use. CONCLUSIONS: Results are consistent
      with the Cochrane Review in that single use hydrophilic coated catheters may not
      decrease the incidence of symptomatic urinary tract infection in community
      dwelling chronic intermittent catheterization users when compared to clean
      multiple use polyvinylchloride catheters.

PMID- 25584994
TI  - Cardiovascular autonomic neuropathy, erectile dysfunction and lower urinary tract
      symptoms in men with type 1 diabetes: findings from the DCCT/EDIC.
AB  - PURPOSE: We evaluated the association between cardiovascular autonomic
      neuropathy, and erectile dysfunction and lower urinary tract symptoms in men with
      type 1 diabetes. MATERIALS AND METHODS: Male type 1 diabetes participants (635)
      in the DCCT/EDIC were studied. Cardiovascular autonomic neuropathy was assessed
      by standardized cardiovascular reflex tests including changes in respiratory rate
      variation with deep breathing, Valsalva maneuver (Valsalva ratio) and changes in
      supine to standing diastolic blood pressure. Erectile dysfunction was assessed by
      a proxy item from the International Index of Erectile Function, and lower urinary
      tract symptoms were assessed with the AUASI (American Urological Association
      Symptom Index). Multivariable logistic regression models estimated the
      association between cardiovascular autonomic neuropathy and erectile dysfunction
      and/or lower urinary tract symptoms, adjusting for time weighted glycemic
      control, blood pressure, age and other covariates. RESULTS: Men in whom erectile
      dysfunction and/or lower urinary tract symptoms developed during EDIC had a
      significantly lower respiratory rate variation and Valsalva ratio at DCCT
      closeout and EDIC year 16/17 compared to those without erectile dysfunction or
      lower urinary tract symptoms. In adjusted analysis, participants with
      cardiovascular autonomic neuropathy had 2.65 greater odds of erectile dysfunction
      and lower urinary tract symptoms (95% CI 1.47-4.79). CONCLUSIONS: These data
      suggest that cardiovascular autonomic neuropathy predicts the development of
      urological complications in men with long-standing type 1 diabetes. Studies
      evaluating the mechanisms contributing to these interactions are warranted for
      targeting effective prevention or treatment.

PMID- 25584997
TI  - [The most cited articles in volume 39 of Psychiatrische Praxis -
      congratulations!].

PMID- 25584996
TI  - Intraoperative Fluorescence Imaging for Detection of Sentinel Lymph Nodes and
      Lymphatic Vessels during Open Prostatectomy using Indocyanine Green.
AB  - PURPOSE: We investigated the feasibility and validity of intraoperative
      fluorescence imaging using indocyanine green for the detection of sentinel lymph
      nodes and lymphatic vessels during open prostatectomy. MATERIALS AND METHODS:
      Indocyanine green was injected into the prostate under transrectal ultrasound
      guidance just before surgery. Intraoperative fluorescence imaging was performed
      using a near-infrared camera system in 66 consecutive patients with clinically
      localized prostate cancer after a 10-patient pilot test to optimize indocyanine
      green dosing, observation timing and injection method. Lymphatic vessels were
      visualized and followed to identify the sentinel lymph nodes. Confirmatory pelvic
      lymph node dissection including all fluorescent nodes and open radical
      prostatectomy were performed in all patients. RESULTS: Lymphatic vessels were
      successfully visualized in 65 patients (98%) and sentinel lymph nodes in 64
      patients (97%). Sentinel lymph nodes were located in the obturator fossa,
      internal and external iliac regions, and rarely in the common iliac and presacral
      regions. A median of 4 sentinel lymph nodes per patient was detected. Three
      lymphatic pathways, the paravesical, internal and lateral routes, were
      identified. Pathological examination revealed metastases to 9 sentinel lymph
      nodes in 6 patients (9%). All pathologically positive lymph nodes were detected
      as sentinel lymph nodes using this imaging. No adverse reactions due to the use
      of indocyanine green were observed. CONCLUSIONS: Intraoperative fluorescence
      imaging using indocyanine green during open prostatectomy enables the detection
      of lymphatic vessels and sentinel lymph nodes with high sensitivity. This novel
      method is technically feasible, safe and easy to apply with minimal additional
      operative time.

PMID- 25584998
TI  - [Innovative treatment in psychiatry - a chance for integrated health care].

PMID- 25584999
TI  - [The debate: site of the cultivated academic duel - our gratitude to Martin
      Hambrecht!].

PMID- 25585000
TI  - [Transparency alone is not sufficient for the management of conflicts of interest
      - pro].

PMID- 25585001
TI  - [Transparency alone is not sufficient for the management of conflicts of interest
      - contra].

PMID- 25585002
TI  - [Reports from the Federal Directors Conference].

PMID- 25585003
TI  - Enzyme engineering in the context of novel pathways and products.
AB  - In recent years, enzyme engineering was used to fine-tune a diverse set of
      proteins to realize new biosynthetic pathways and gain access to novel products.
      However, enzymes in nature do not always meet the required demands in terms of
      activity, selectivity and stability. In these cases enzyme engineering has been
      used to improve the enzyme properties, which facilitated the development of
      tailor-made functional biocatalysts, even beyond their natural capabilities.
      Examples can be found in the three main areas of chemical biotechnology: single
      step biocatalysis, metabolic engineering and enzymatic cascades. In this review
      we highlight recently published work in all of these three fields and emphasize
      the main trends and differences. 

PMID- 25585004
TI  - Pharmacokinetics of tranexamic acid in neonates, infants, and children undergoing
      cardiac surgery with cardiopulmonary bypass.
AB  - BACKGROUND: Tranexamic acid (TXA) is one of the most commonly used
      antifibrinolytic medications in children undergoing repair of congenital heart
      defects. However, a pharmacokinetics analysis of TXA has never been performed in
      neonates or young children undergoing complex cardiac surgeries using
      cardiopulmonary bypass, hypothermia, circulatory arrest, and ultrafiltration. A
      comprehensive pharmacokinetics study was performed in this patient population.
      METHODS: Fifty-five patients ranging from 2 days through 4 yr old were
      categorized into three groups: children less than 2 months old, infants 2 months
      to 1 yr old, and children greater than 1 yr old and weighing up to 20 kg. TXA was
      given as a bolus of 100 mg/kg followed by an infusion of 10 mg . kg . h
      throughout the surgery. A dose of 100 mg/kg was placed in the cardiopulmonary
      bypass prime. A total of 16 to 18 samples were obtained from all patients
      throughout surgery. Plasma TXA concentrations were measured by high-performance
      liquid chromatography and modeled under a nonlinear mixed-effects framework with
      a two-compartment structural model. RESULTS: Cardiopulmonary bypass had a
      statistically significant impact on all pharmacokinetic parameters. Age was a
      better covariate than body weight, affecting both the distribution and the
      elimination of TXA. However, weight performed well in some cases. Other
      covariates including body surface area, pump prime volume, ultrafiltrate volume,
      and body temperature did not improve the model. CONCLUSIONS: This TXA
      pharmacokinetic analysis is reported for the first time in neonates and young
      children undergoing complex cardiac surgeries with cardiopulmonary bypass. Dosing
      recommendations are provided as guidance for maintaining desired target
      concentrations.

PMID- 25585006
TI  - Design and development of novel Mycobacterium tuberculosis L-alanine
      dehydrogenase inhibitors.
AB  - In the present study, we used crystal structure of MTB L-AlaDH protein complex
      with N6-methyl adenosine for structure based virtual screening of in house
      database to identify new small molecule inhibitors for MTB-L-AlaDH. Two molecules
      identified as better leads and were modified synthetically to obtain thirty novel
      analogues belonging to 2-iminothiazolidine-4-ones and 4,5,6,7
      tetrahydrothieno[2,3-c]pyridine-3-carboxamides. Among the screened compounds four
      (4n, 4o, 12 and 14) emerged as potent inhibitors displaying IC50 values ranging
      from 0.58 +/- 0.02 to 1.74 +/- 0.03 MUM against MTB-L-AlaDH and were non
      cytotoxic at 50 MUM. Some of these synthesized compounds also exhibited good
      activity against nutrient starved dormant MTB cells. The most potent inhibitors
      were found to stabilize the protein which was confirmed biophysically through
      differential scanning fluorimetry.

PMID- 25585005
TI  - Enhanced effects of isoflurane on the long QT syndrome 1-associated A341V mutant.
AB  - BACKGROUND: The impact of volatile anesthetics on patients with inherited long QT
      syndrome (LQTS) is not well understood. This is further complicated by the
      different genotypes underlying LQTS. No studies have reported on the direct
      effects of volatile anesthetics on specific LQTS-associated mutations. We
      investigated the effects of isoflurane on a common LQTS type 1 mutation, A341V,
      with an unusually severe phenotype. METHODS: Whole cell potassium currents (IKs)
      were recorded from HEK293 and HL-1 cells transiently expressing/coexpressing wild
      type KCNQ1 (alpha-subunit), mutant KCNQ1, wild-type KCNE1 (beta-subunit), and
      fusion KCNQ1 + KCNE1. Current was monitored in the absence and presence of
      clinically relevant concentration of isoflurane (0.54 +/- 0.05 mM, 1.14 vol %).
      Computer simulations determined the resulting impact on the cardiac action
      potential. RESULTS: Isoflurane had significantly greater inhibitory effect on
      A341V + KCNE1 (62.2 +/- 3.4%, n = 8) than on wild-type KCNQ1 + KCNE1 (40.7 +/-
      4.5%; n = 9) in transfected HEK293 cells. Under heterozygous conditions,
      isoflurane inhibited A341V + KCNQ1 + KCNE1 by 65.2 +/- 3.0% (n = 13) and wild
      type KCNQ1 + KCNE1 (2:1 ratio) by 32.0 +/- 4.5% (n = 11). A341V exerted a
      dominant negative effect on IKs. Similar differential effects of isoflurane were
      also observed in experiments using the cardiac HL-1 cells. Mutations of the
      neighboring F340 residue significantly attenuated the effects of isoflurane, and
      fusion proteins revealed the modulatory effect of KCNE1. Action potential
      simulations revealed a stimulation frequency-dependent effect of A341V.
      CONCLUSIONS: The LQTS-associated A341V mutation rendered the IKs channel more
      sensitive to the inhibitory effects of isoflurane compared to wild-type IKs in
      transfected cell lines; F340 is a key residue for anesthetic action.

PMID- 25585007
TI  - Design, synthesis and pharmacological evaluation of novel N-(2-(1, 1-dimethyl-5,
      7-dioxo-4, 6-diazaspiro[2.4]heptan-6-yl)ethyl) sulfonamide derivatives as
      potential anticonvulsant agents.
AB  - A series of new N-(2-(1,1-dimethyl-5,7-dioxo-4,6-diazaspiro[2.4]heptan-6
      yl)ethyl) sulfonamide derivatives (8a-i) and ethyl 2,2-dimethyl-1-(3-(2
      (sulfonamido)ethyl)ureido) cyclopropanecarbox-ylate derivatives (9a-i) were
      designed, synthesized and evaluated for their anticonvulsant activities using
      maximal electroshock shock (MES) and subcutaneous pentylenetetrazole (scPTZ)
      seizure models in mice. N-(2-(1,1-dimethyl-5,7-dioxo-4,6-diazaspiro[2.4]heptan-6
      yl)ethyl)-4-fluoroben- zenesulfonamide (8f) and N-(2-(1,1-dimethyl-5,7-dioxo-4,6
      diazaspiro[2.4]heptan-6-yl)ethyl)-4- methylbenzenesulfonamide (8e) have shown
      promising anticonvulsant activities in MES model. The most active compound 8f has
      shown the MES-induced seizures with ED50 value of 28.05 mg/kg and TD50 value of
      561 mg/kg after intraperitoneal injection to mice, which provided compound 8f
      with a protective index (TD50/ED50) of 20 in the MES test. Further, rotarod
      toxicity method was used to study the acute neurotoxicity profile of selected
      compounds.

PMID- 25585008
TI  - Further insights into the SAR of alpha-substituted cyclopropylamine derivatives
      as inhibitors of histone demethylase KDM1A.
AB  - Epigenetics alterations including histone methylation and acetylation, and DNA
      methylation, are thought to play important roles in the onset and progression of
      cancer in numerous tumour cell lines. Lysine-specific demethylase 1 (LSD1 or
      KDM1A) is highly expressed in different cancer types and inhibiting KDM1A
      activity seems to have high therapeutic potential in cancer treatment. In the
      recent years, several inhibitors of KDM1A have been prepared and disclosed. The
      majority of these derivatives were designed based on the structure of
      tranylcypromine, as the cyclopropane core is responsible for the covalent
      interaction between the inhibitor and the catalytic domain of KDM proteins. In
      this study, we have further extended the SAR regarding compounds 1a-e, which were
      recently found to inhibit KDM1A with good activity. The decoration of the phenyl
      ring at the beta-position of the cyclopropane ring with small functional groups,
      mostly halogenated, and in particular at the meta position, led to a significant
      improvement of the inhibitory activity against KDM1A, as exemplified by compound
      44a, which has a potency in the low nanomolar range (31 nM). 

PMID- 25585009
TI  - Synthesis of novel inhibitors of alpha-glucosidase based on the benzothiazole
      skeleton containing benzohydrazide moiety and their molecular docking studies.
AB  - In an effort to design and synthesize a new class of alpha-glucosidase inhibitor,
      we synthesized benzothiazole hybrid having benzohydrazide moiety (5). Compound 5
      was reacted with various substituted aryl aldehyde to generate a small library of
      compounds 6-35. Synthesis of compounds was confirmed by the spectral information.
      These compounds were screened for their alpha-glucosidase activity. They showed a
      varying degree of alpha-glucosidase inhibition with IC50 values ranging between
      5.31 and 53.34 MUM. Compounds 6, 7, 9-16, 19, 21-30, 32-35 showed superior
      activity as compared to standard acarbose (IC50 = 906 +/- 6.3 MUM). This has
      identified a new class of alpha-glucosidase inhibitors. The predicted physico
      chemical properties indicated the drug appropriateness for most of these
      compounds, as they obey Lipinski's rule of five (RO5). A hybrid B3LYP density
      functional theory (DFT) was employed for energy, minimization of 3D structures
      for all synthetic compounds using 6-311 + G(d,p) basis sets followed by molecular
      docking to explore their interactions with human intestinal C- and N-terminal
      domains of alpha-glucosidase. All compounds bind to the prospective allosteric
      site of the C- terminal domain, and consequently, may be considered as mixed
      inhibitors. It was hypothesized that both the dipole moment and H-bond
      interactions govern the biological activation of these compounds.

PMID- 25585010
TI  - HIV-1 Nef: a master manipulator of the membrane trafficking machinery mediating
      immune evasion.
AB  - BACKGROUND: Many viral genomes encode a limited number of proteins, illustrating
      their innate efficiency in bypassing host immune surveillance. This concept of
      genomic efficiency is exemplified by the 9 kb RNA genome of human
      immunodeficiency virus 1 (HIV-1), encoding 15 proteins sub-divided according to
      function. The enzymatic group includes proteins such as the drug targets reverse
      transcriptase and protease. In contrast, the accessory proteins lack any known
      enzymatic or structural function, yet are essential for viral fitness and HIV-1
      pathogenesis. Of these, the HIV-1 accessory protein Nef is a master manipulator
      of host cellular processes, ensuring efficient counterattack against the host
      immune response, as well as long-term evasion of immune surveillance. In
      particular, the ability of Nef to downmodulate major histocompatibility complex
      class I (MHC-I) is a key cellular event that enables HIV-1 to bypass the host's
      defenses by evading the adaptive immune response. SCOPE OF REVIEW: In this
      article, we briefly review how various pathogenic viruses control cell-surface
      MHC-I, and then focus on the mechanisms and implications of HIV-1 Nef-mediated
      MHC-I downregulation via modulation of the host membrane trafficking machinery.
      CONCLUSION: The extensive interaction network formed between Nef and numerous
      membrane trafficking regulators suggests that Nef's role in evading the immune
      surveillance system intersects multiple host membrane trafficking pathways.
      SIGNIFICANCE: Nef's ability to evade the immune surveillance system is linked to
      AIDS pathogenesis. Thus, a complete understanding of the molecular pathways that
      are subverted by Nef in order to downregulate MHC-I will enhance our
      understanding of HIV-1's progression to AIDS.

PMID- 25585011
TI  - Computational perspective and evaluation of plausible catalytic mechanisms of
      peptidyl-prolyl cis-trans isomerases.
AB  - BACKGROUND: Peptidyl prolyl cis-trans isomerization of the protein backbone is
      involved in the regulation of many biological processes. Cis-trans isomerization
      is notoriously slow and is catalyzed by a family of cis-trans peptidyl prolyl
      isomerases (PPIases) that have been implicated in many diseases. A general
      consensus on how these enzymes speed up prolyl isomerization has not been reached
      after decades of both experimental and computational studies. SCOPE OF REVIEW:
      Computational studies carried out to understand the catalytic mechanism of the
      prototypical FK506 binding protein 12, Cyclophilin A and peptidyl-prolyl cis
      trans isomerase NIMA-interacting 1 (Pin1) are reviewed. A summary and an
      evaluation of the implications of the proposed mechanisms from computational
      studies are presented. MAJOR CONCLUSIONS: The analysis of computational studies
      and evaluation of the proposed mechanisms provide a general consensus and a
      better understanding of PPIase catalysis. The speedup of the rate of peptidyl
      prolyl isomerization by PPIases can be best described by a catalytic mechanism in
      which the substrate in transition state configuration is stabilized. The enzymes
      preferentially bind the transition state configuration of the substrate relative
      to the cis conformation, which in most cases is bound better than the trans
      conformation of the substrate. Stabilization of the transition state
      configuration of the substrate leads to a lower free energy barrier and a faster
      rate of isomerization when compared to the uncatalyzed isomerization reaction.
      GENERAL SIGNIFICANCE: Fully understanding the catalytic mechanism of PPIases has
      broad implications for drug design, elucidation of the molecular basis of many
      diseases, protein engineering, and enzyme catalysis in general. This article is
      part of a Special Issue entitled Proline-directed Foldases: Cell Signaling
      Catalysts and Drug Targets.

PMID- 25585013
TI  - Targeting the sigma-1 receptor chaperone in the treatment of perinatal brain
      injury.
AB  - Glutamate-induced excitotoxicity via the N-methyl-d-aspartate (NMDA) receptor is
      an important factor in the pathogenesis of perinatal brain injury. The sigma-1
      receptor on the endoplasmic reticulum (ER) has been known to affect the function
      of the NMDA receptor. 4-Phenyl-1-(4-phenylbutyl)piperidine (PPBP) has been
      investigated as a sigma-1 receptor agonist for several decades. An article using
      PPBP in a model of preterm brain injury was published in Experimental Neurology.
      The authors reported that PPBP protected against glutamate-induced excitotoxicity
      in primary hippocampal neurons. Furthermore, the systemic administration of PPBP
      significantly reduced microglial activation and lesion size in cortical gray and
      white matter after the excitotoxic insult in neonatal mice. This study suggests
      that sigma-1 receptor agonists could be potential preventive and therapeutic
      drugs for perinatal brain injury, although a pharmacological experiment using a
      sigma-1 receptor antagonist was not performed. This commentary aims to highlights
      the key findings of this article in a broader context, emphasizing the future
      potential therapeutic applications in patients with perinatal brain injury. 

PMID- 25585012
TI  - Aquaporin-1 water permeability as a novel determinant of axonal regeneration in
      dorsal root ganglion neurons.
AB  - Dorsal root ganglion (DRG) neurons transduce peripheral pain signals through
      small-diameter, non-myelinated C-fibers, which, when injured, can regenerate to
      restore pain sensation. Water channel aquaporin-1 (AQP1) is expressed at the
      plasma membrane of cell bodies and axons of DRG neurons, where it modulates the
      sensing of certain types of pain. Here, we found that AQP1 is also involved in
      DRG axonal growth and regeneration by a mechanism that may involve water
      transport-facilitated extension of axonal outgrowths. Spontaneous and nerve
      growth factor-stimulated axonal extension was reduced in cultures of AQP1
      deficient DRG neurons and DRG explants compared to the wildtype. Axonal growth in
      AQP1-deficient DRG cultures was rescued by transfection with AQP1 or a different
      water-transporting AQP (AQP4), but not by a non-water-transporting AQP1 mutant.
      Following sciatic nerve compression injury AQP1 expression was increased in DRG
      neurons in wildtype mice, and DRG axonal growth was impaired in AQP1-deficient
      mice. Our results indicate AQP1 as a novel determinant of DRG axonal regeneration
      and hence a potential therapeutic target to accelerate neuronal regeneration. 

PMID- 25585015
TI  - Atropisomerism in amidinoquinoxaline N-oxides: effect of the ring size and
      substituents on the enantiomerization barriers.
AB  - The atropisomerism of novel 2,3-dihydro-1H-pyrimido[1,2-a]quinoxaline 6-oxides 1
      bearing dissymmetric (ortho-substituted) 5-aryl residues and the homologous 1,2
      dihydroimidazo[1,2-a]quinoxaline 5-oxides 2 was investigated. The existence of a
      chiral axis was demonstrated for compound 1a by X-ray diffraction and by DFT
      calculations of the ground state geometry. The resolution of the atropisomeric
      enantiomers on chiral stationary phases is reported. The barriers to
      enantiomerization were determined by off-line racemization studies and/or by
      treatment of the plateau-shaped chromatograms during chromatography on chiral
      support. A clear ring size effect was evidenced. In all cases, six-membered
      amidine derivatives 1 showed higher barriers than the corresponding lower
      homologues 2, which also display lower sensitivity to the substituent size.
      Transition states for the interconversion of the atropisomers were located using
      DFT calculations, and involved the interaction of the ortho substituent with the
      formally sp(2) nitrogen in the amidine moiety. In contrast, in the most favored
      enantiomerization transition state of the 2-nitro derivative the ortho
      substituent is close to the N-oxide group. 

PMID- 25585014
TI  - G-CSF attenuates neuroinflammation and stabilizes the blood-brain barrier via the
      PI3K/Akt/GSK-3beta signaling pathway following neonatal hypoxia-ischemia in rats.
AB  - OBJECTIVE: Neonatal hypoxia occurs in approximately 60% of premature births and
      is associated with a multitude of neurological disorders. While various
      treatments have been developed, translating them from bench to bedside has been
      limited. We previously showed G-CSF administration was neuroprotective in a
      neonatal hypoxia-ischemia rat pup model, leading us to hypothesize that G-CSF
      inactivation of GSK-3beta via the PI3K/Akt pathway may attenuate
      neuroinflammation and stabilize the blood-brain barrier (BBB). METHODS: P10
      Sprague-Dawley rat pups were subjected to unilateral carotid artery ligation
      followed by hypoxia for 2.5h. We assessed inflammation by measuring expression
      levels of IKKbeta, NF-kappaB, TNF-alpha, IL-1beta, IL-10, and IL-12 as well as
      neutrophil infiltration. BBB stabilization was evaluated by measuring Evans blue
      extravasation, and Western blot analysis of Claudin-3, Claudin-5, ICAM-1, and
      VCAM-1. MEASUREMENTS AND MAIN RESULTS: First, the time course study showed that p
      beta-catenin/beta-catenin, IKKbeta, and NF-kappaB expression levels peaked at 48h
      post-HI. The knockdown of GSK-3beta with siRNA prevented the HI-induced increase
      of p-beta-catenin/beta-catenin, IKKbeta, and NF-kappaB expression levels 48h
      after HI. G-CSF treatment reduced brain water content and neuroinflammation by
      downregulating IKKbeta, NF-kappaB, TNF-alpha, IL-1beta, and IL-12 and
      upregulating IL-10, thereby reducing neutrophil infiltration. Additionally, G-CSF
      stabilizes the BBB by downregulating VCAM-1 and ICAM-1, as well as upregulating
      Claudins 3 and 5 in endothelial cells. G-CSFR knockdown by siRNA and Akt
      inhibition by Wortmannin reversed G-CSF's neuroprotective effects. CONCLUSIONS:
      We demonstrate G-CSF plays a pivotal role in attenuating neuroinflammation and
      BBB disruption following HI by inactivating GSK-3beta through the PI3K/Akt
      pathway.

PMID- 25585016
TI  - Selective scission of C-O and C-C bonds in ethanol using bimetal catalysts for
      the preferential growth of semiconducting SWNT arrays.
AB  - For the application of single-walled carbon nanotubes (SWNTs) to electronic and
      optoelectronic devices, techniques to obtain semiconducting SWNT (s-SWNT) arrays
      are still in their infancy. We have developed herein a rational approach for the
      preferential growth of horizontally aligned s-SWNT arrays on a ST-cut quartz
      surface through the selective scission of C-O and C-C bonds of ethanol using
      bimetal catalysts, such as Cu/Ru, Cu/Pd, and Au/Pd. For a common carbon source,
      ethanol, a reforming reaction occurs on Cu or Au upon C-C bond breakage and
      produces C(ads) and CO, while a deoxygenating reaction occurs on Ru or Pd through
      C-O bond breaking resulting in the production of O(ads) and C2H4. The produced
      C2H4 by Ru or Pd can weaken the oxidative environment through decomposition and
      the neutralization of O(ads). When the bimetal catalysts with an appropriate
      ratio were used, the produced C(ads) and C2H4 can be used as carbon source for
      SWNT growth, and O(ads) promotes a suitable and durable oxidative environment to
      inhibit the formation of metallic SWNTs (m-SWNTs). Finally, we successfully
      obtained horizontally aligned SWNTs on a ST-cut quartz surface with a density of
      4-8 tubes/MUm and an s-SWNT ratio of about 93% using an Au/Pd (1:1) catalyst. The
      synergistic effects in bimetallic catalysts provide a new mechanism to control
      the growth of s-SWNTs.

PMID- 25585019
TI  - Diffusion tensor characteristics of gyrencephaly using high resolution diffusion
      MRI in vivo at 7T.
AB  - Gyrification of the human cerebral cortex allows for the surface expansion that
      accommodates many more cortical neurons in comparison to other mammals. For
      neuroimaging, however, it forms a feature that complicates analysis. For example,
      it has long been established that cortical layers do not occupy the same depth in
      gyri and sulci. Recently, in vivo diffusion imaging has provided insights into
      the fibre architecture of the cortex, usually showing radial tensor orientations.
      This makes it relevant to investigate whether cortical diffusion tensor metrics
      depend on the gyral pattern. High-resolution (1mm isotropic) diffusion weighted
      MRI of the medial wall of the hemispheres was performed at 7 T. Diffusion data
      were resampled to surfaces in the cortex and underlying white matter, where the
      cortical surfaces obeyed the equivolume principle for cortical laminae over the
      cortical curvature. Diffusion tensor metrics were averaged over bins of curvature
      to obtain maps of characteristic patterns in the gyrus. Diffusivity, anisotropy
      and radiality varied with curvature. Radiality was maximal in intermediate layers
      of the cortex next to the crown of the gyrus, not in white matter or on the
      crown. In the fundus, the deep cortical layers had tangential tensor
      orientations. In the white matter, tensor orientation changed from radial on the
      crown to tangential under the banks and fundus. White matter anisotropy gradually
      increased from the crown to the fundus. The characteristic pattern in the gyrus
      demonstrated here is in accordance with ex vivo diffusion MR microscopy and
      histological studies. The results indicate the necessity of taking into account
      the gyral pattern when cortical diffusion data is analysed. Additionally, the
      data suggest a confound for tractography approaches when reaching the gyrus,
      resulting in a possible bias towards the gyral crown. The implications for
      mechanisms that could drive cortical folding are discussed.

PMID- 25585018
TI  - Effects of rejecting diffusion directions on tensor-derived parameters.
AB  - Diffusion Tensor Imaging (DTI) is adversely affected by subject motion. It is
      necessary to discard the corrupted images before diffusion parameter estimation.
      However, the consequences of rejecting those images are not well understood. In
      this study, we investigated the effects of excluding one or more volumes of
      diffusion weighted images by analyzing the changes in fractional anisotropy (FA),
      mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and the
      primary eigenvector (V1). Based on the full set of diffusion images acquired by
      the Jones30 diffusion scheme, we generated incomplete sets of at least six in
      three different ways: random, uniform and clustered rejections. The results
      showed that MD was not significantly affected by rejecting diffusion directions.
      In the cases of random rejections, FA, AD, RD and V1 were overestimated more
      greatly with increasing number of rejections and the overestimations were worse
      in low FA regions than high FA regions. For uniform rejections, at which the
      remaining diffusion directions are evenly distributed on a sphere, little change
      was observed in FA and in V1. Clustered rejections, on the other hand, displayed
      the most significant overestimation of the parameters, and the resulting accuracy
      depended on the relative orientation of the underlying fibers with respect to the
      excluded directions. In practice, if diffusion direction data is excluded, it is
      important to note the number and location of directions rejected, in order to
      make a more precise analysis of the data. 

PMID- 25585017
TI  - A DCM study of spectral asymmetries in feedforward and feedback connections
      between visual areas V1 and V4 in the monkey.
AB  - This paper reports a dynamic causal modeling study of electrocorticographic
      (ECoG) data that addresses functional asymmetries between forward and backward
      connections in the visual cortical hierarchy. Specifically, we ask whether
      forward connections employ gamma-band frequencies, while backward connections
      preferentially use lower (beta-band) frequencies. We addressed this question by
      modeling empirical cross spectra using a neural mass model equipped with
      superficial and deep pyramidal cell populations-that model the source of forward
      and backward connections, respectively. This enabled us to reconstruct the
      transfer functions and associated spectra of specific subpopulations within
      cortical sources. We first established that Bayesian model comparison was able to
      discriminate between forward and backward connections, defined in terms of their
      cells of origin. We then confirmed that model selection was able to identify
      extrastriate (V4) sources as being hierarchically higher than early visual (V1)
      sources. Finally, an examination of the auto spectra and transfer functions
      associated with superficial and deep pyramidal cells confirmed that forward
      connections employed predominantly higher (gamma) frequencies, while backward
      connections were mediated by lower (alpha/beta) frequencies. We discuss these
      findings in relation to current views about alpha, beta, and gamma oscillations
      and predictive coding in the brain. 

PMID- 25585021
TI  - Aging alterations in whole-brain networks during adulthood mapped with the
      minimum spanning tree indices: the interplay of density, connectivity cost and
      life-time trajectory.
AB  - The organizational network changes in the human brain across the lifespan have
      been mapped using functional and structural connectivity data. Brain network
      changes provide valuable insights into the processes underlying senescence.
      Nonetheless, the altered network density in the elderly severely compromises the
      usefulness of network analysis to study the aging brain. We successfully
      circumvented this problem by focusing on the critical structural network
      backbone, using a robust tree representation. Whole-brain networks' minimum
      spanning trees were determined in a dataset of diffusion-weighted images from 382
      healthy subjects, ranging in age from 20.2 to 86.2 years. Tree-based metrics were
      compared with classical network metrics. In contrast to the tree-based metrics,
      classical metrics were highly influenced by age-related changes in network
      density. Tree-based metrics showed linear and non-linear correlation across
      adulthood and are in close accordance with results from previous
      histopathological characterizations of the changes in white matter integrity in
      the aging brain.

PMID- 25585020
TI  - Quantile rank maps: a new tool for understanding individual brain development.
AB  - We propose a novel method for neurodevelopmental brain mapping that displays how
      an individual's values for a quantity of interest compare with age-specific
      norms. By estimating smoothly age-varying distributions at a set of brain regions
      of interest, we derive age-dependent region-wise quantile ranks for a given
      individual, which can be presented in the form of a brain map. Such quantile rank
      maps could potentially be used for clinical screening. Bootstrap-based confidence
      intervals are proposed for the quantile rank estimates. We also propose a
      recalibrated Kolmogorov-Smirnov test for detecting group differences in the age
      varying distribution. This test is shown to be more robust to model
      misspecification than a linear regression-based test. The proposed methods are
      applied to brain imaging data from the Nathan Kline Institute Rockland Sample and
      from the Autism Brain Imaging Data Exchange (ABIDE) sample. 

PMID- 25585022
TI  - Waxholm Space atlas of the rat brain hippocampal region: three-dimensional
      delineations based on magnetic resonance and diffusion tensor imaging.
AB  - Atlases of the rat brain are widely used as reference for orientation, planning
      of experiments, and as tools for assigning location to experimental data.
      Improved quality and use of magnetic resonance imaging (MRI) and other
      tomographical imaging techniques in rats have allowed the development of new
      three-dimensional (3-D) volumetric brain atlas templates. The rat hippocampal
      region is a commonly used model for basic research on memory and learning, and
      for preclinical investigations of brain disease. The region features a complex
      anatomical organization with multiple subdivisions that can be identified on the
      basis of specific cytoarchitectonic or chemoarchitectonic criteria. We here
      investigate the extent to which it is possible to identify boundaries of
      divisions of the hippocampal region on the basis of high-resolution MRI contrast.
      We present the boundaries of 13 divisions, identified and delineated based on
      multiple types of image contrast observed in the recently published Waxholm Space
      MRI/DTI template for the Sprague Dawley rat brain (Papp et al., Neuroimage 97:374
      386, 2014). The new detailed delineations of the hippocampal formation and
      parahippocampal region (Waxholm Space atlas of the Sprague Dawley rat brain,
      v2.0) are shared via the INCF Software Center (http://software.incf.org/), where
      also the MRI/DTI reference template is available. The present update of the
      Waxholm Space atlas of the rat brain is intended to facilitate interpretation,
      analysis, and integration of experimental data from this anatomically complex
      region. 

PMID- 25585023
TI  - Fluorescence imaging of dendritic spines of Golgi-Cox-stained neurons using
      brightening background.
AB  - We report a novel fluorescence imaging approach to imaging nonfluorescence
      labeled biological tissue samples. The method was demonstrated by imaging neurons
      in Golgi-Cox-stained and epoxy-resin-embedded samples through the excitation of
      the background fluorescence of the specimens. The dark neurons stood out clearly
      against background fluorescence in the images, enabling the tracing of a single
      dendritic spine using both confocal and wide-field fluorescence microscopy. The
      results suggest that the reported fluorescence imaging method would provide an
      effective alternative solution to image nonfluorescence-labeled samples, and it
      allows tracing the dendritic spine structure of neurons.

PMID- 25585024
TI  - Analysis of optimum conditions of depolarization imaging by polarization
      sensitive optical coherence tomography in the human retina.
AB  - Measurement and imaging of depolarization by polarization-sensitive optical
      coherence tomography (PS-OCT) requires averaging of Stokes vector elements within
      two- or three-dimensional (3-D) evaluation windows to obtain the degree of
      polarization uniformity (DOPU). By use of a PS-OCT system with an integrated
      retinal tracker, we analyze optimum conditions for depolarization imaging, data
      processing, and segmentation of depolarizing tissue in the human retina. The
      trade-offs between figures of merit like DOPU imaging sensitivity, efficiency,
      and susceptibility are evaluated in terms of 3-D resolution. The results are used
      for a new, detailed interpretation of PS-OCT high-resolution images of the human
      retinal pigment epithelium and Bruch's membrane.

PMID- 25585025
TI  - Neopetrocyclamines A and B, polycyclic diamine alkaloids from the sponge
      Neopetrosia cf exigua.
AB  - Two new polycyclic alkaloids, neopetrocyclamines A and B (1 and 2), along with
      the known metabolites papuamine (3) and haliclonadiamine (4), were isolated from
      the Indonesian sponge Neopetrosia cf exigua. Neopetrocyclamine A contains a
      formamidinium moiety, a rare functional group. While these compounds share the
      same basic biosynthetic building blocks, the size of the ring system differs in 1
      and 2 because of the formamidinium moiety. Biological evaluations of 1-4 revealed
      that papuamine is cytotoxic against glioblastoma SF-295 cells (GI50 = 0.8 MUM).

PMID- 25585027
TI  - Mild Rh(III)-catalyzed C7-allylation of indolines with allylic carbonates.
AB  - The rhodium(III)-catalyzed direct allylation of indolines with allylic carbonates
      at room temperature is described. These transformations provide the facile and
      efficient construction of C7-allylated indolic scaffold. 

PMID- 25585026
TI  - TGFbeta1 rapidly activates Src through a non-canonical redox signaling mechanism.
AB  - Transforming growth factor-beta1 (TGF-beta) is involved in multiple cellular
      processes through Src activation. In the canonical pathway, Src activation is
      initiated by pTyr530 dephosphorylation followed by a conformational change
      allowing Tyr419 auto-phosphorylation. A non-canonical pathway in which oxidation
      of cysteine allows bypassing of pTyr530 dephosphorylation has been reported.
      Here, we examined how TGF-beta activates Src in H358 cells, a small cell lung
      carcinoma cell line. TGF-beta increased Src Tyr419 phosphorylation, but
      surprisingly, Tyr530 phosphorylation was increased rather than decreased.
      Vanadate, a protein tyrosine phosphatase inhibitor, stimulated Src activation
      itself, but rather than inhibiting Src activation by TGF-beta, activation by
      vanadate was additive with TGF-beta showing that pTyr530 dephosphorylation was
      not required. Thus, the involvement of the non-canonical oxidative activation was
      suspected. TGF-beta increased extracellular H2O2 transiently while GSH-ester and
      catalase abrogated Src activation by TGF-beta. Apocynin, a NADPH oxidase
      inhibitor, inhibited TGF-beta-stimulated H2O2 production. Furthermore, mutation
      of cysteines to alanine, 248C/A, 277C/A, or 501C/A abrogated, while 490C/A
      significantly reduced, TGF-beta-mediated Src activation. Taken together, the
      results indicate that TGF-beta-mediated Src activation operates largely through a
      redox dependent mechanism, resulting from enhanced H2O2 production through an
      NADPH oxidase and that cysteines 248, 277, 490, and 501 are critical for this
      activation. 

PMID- 25585028
TI  - Effectiveness of genetic cascade screening for familial hypercholesterolaemia
      using a centrally co-ordinated clinical service: an Australian experience.
AB  - BACKGROUND: Familial hypercholesterolaemia (FH) is a co-dominantly inherited
      disorder of low-density lipoprotein (LDL) catabolism, causing elevated LDL
      cholesterol and premature coronary artery disease (CAD). Several guidelines
      recommend genetic cascade screening relatives of probands (index cases) with
      genetically proven FH, but experience in a clinical service setting is limited.
      METHODS: Relatives from 100 index cases with genetically confirmed FH underwent
      genetic and lipid testing via a centralised screening program in Western
      Australia. The program's effectiveness was evaluated as the number of newly
      diagnosed relatives with FH per index case and the proportional reduction in LDL
      cholesterol after treatment. RESULTS: Of 366 relatives tested for FH, 188 (51.4%)
      were found to have a pathogenic mutation. On average, 2 cases were detected per
      index case. Affected relatives were younger and less likely to have physical
      stigmata of FH and premature CAD than index cases (p < 0.001). Of the new cases,
      12.8% had hypertension, 2.7% had diabetes and 16.0% were smokers; 48.4% were
      already on statin therapy and these were older (p < 0.001) and had more vascular
      risk factors and CAD (p < 0.01) than those not on therapy. Significant reductions
      in LDL-cholesterol (-24.3%, p < 0.001) were achieved overall, with previously
      untreated new cases of FH attaining a maximal average reduction of 42.5% in LDL
      cholesterol after drug therapy. Over 90% of subjects were satisfied with
      screening and care. CONCLUSION: Genetic cascade screening co-ordinated by a
      centralised service is an effective and acceptable strategy for detecting FH in
      an Australian setting. A significant proportion of new cases exhibit other CAD
      risk factors and are already on statins, but have not received a prior diagnosis
      of FH.

PMID- 25585030
TI  - Scoring of coronary artery calcium scans: history, assumptions, current
      limitations, and future directions.
AB  - Coronary artery calcium (CAC) scanning is a reliable, noninvasive technique for
      estimating overall coronary plaque burden and for identifying risk for future
      cardiac events. Arthur Agatston and Warren Janowitz published the first technique
      for scoring CAC scans in 1990. Given the lack of available data correlating CAC
      with burden of coronary atherosclerosis at that time, their scoring algorithm was
      remarkable, but somewhat arbitrary. Since then, a few other scoring techniques
      have been proposed for the measurement of CAC including the Volume score and Mass
      score. Yet despite new data, little in this field has changed in the last 15
      years. The main focus of our paper is to review the implications of the current
      approach to scoring CAC scans in terms of correlation with the central disease -
      coronary atherosclerosis. We first discuss the methodology of each available
      scoring system, describing how each of these scores make important indirect
      assumptions in the way they account (or do not account) for calcium density,
      location of calcium, spatial distribution of calcium, and
      microcalcification/emerging calcium that might limit their predictive power.
      These assumptions require further study in well-designed, large event-driven
      studies. In general, all of these scores are adequate and are highly correlated
      with each other. Despite its age, the Agatston score remains the most extensively
      studied and widely accepted technique in both the clinical and research settings.
      After discussing CAC scoring in the era of contrast enhanced coronary CT
      angiography, we discuss suggested potential modifications to current CAC scanning
      protocols with respect to tube voltage, tube current, and slice thickness which
      may further improve the value of CAC scoring. We close with a focused discussion
      of the most important future directions in the field of CAC scoring. 

PMID- 25585029
TI  - The association of resistin with cardiovascular disease in the Multi-Ethnic Study
      of Atherosclerosis.
AB  - OBJECTIVE: To describe the relationship between circulating resistin levels and
      cardiovascular diseases (CVD) and all-cause death in a multi-ethnic cohort.
      METHODS AND RESULTS: We studied 1913 participants from the Multi-Ethnic Study of
      Atherosclerosis with measurements of plasma resistin levels. Absolute proportions
      experiencing new-onset atrial fibrillation (AF), atherosclerotic CVD (myocardial
      infarction, angina, resuscitated cardiac arrest, stroke), heart failure (HF), and
      all-cause death were calculated for each quartile of resistin. We used adjusted
      Cox proportional regression modeling resistin as a continuous variable per
      standard deviation of log-transformed resistin and secondarily as a categorical
      variable using resistin quartiles. Results were stratified by sex and
      race/ethnicity. The mean age of the population was 64.5 +/- 10 years with half
      being female and a median resistin concentration of 15.1 ng/mL (11.9-19.1). Mean
      follow-up time was 7.2 +/- 1.8 years. There was a graded increase in the
      occurrence of all outcomes across increasing quartiles of resistin. Modeled as a
      continuous variable, after adjustment for anthropomorphic measures, traditional
      risk factors, markers of inflammation, and other adipokines, significant
      associations were noted for HF (HR 1.4, CI 1.0-2.0), hard and all CVD (HR 1.3,
      1.1-1.7 and 1.3, 1.1-1.6, respectively), and CHD (HR 1.31, 1.0-1.6), but not for
      AF or death. Significant interaction terms were noted between resistin and race,
      with Hispanic race/ethnicity showing the strongest relationship between resistin
      and outcomes. CONCLUSIONS: In an ethnically diverse population without known CVD
      at baseline, there was a strong, independent association between higher resistin
      levels and incident CVD, CHD and HF.

PMID- 25585031
TI  - Expected impact of applying new 2013 AHA/ACC cholesterol guidelines criteria on
      the recommended lipid target achievement after acute coronary syndromes.
AB  - BACKGROUND: 2013 AHA/ACC guidelines on the treatment of cholesterol advised to
      tailor high-intensity statin after ACS, while previous ATP-III recommended
      titration of statin to reach low-density lipoprotein cholesterol (LDL-C) targets.
      We simulated the impact of this change of paradigm on the achievement of
      recommended targets. METHODS: Among a prospective cohort study of consecutive
      patients hospitalized for ACS from 2009 to 2012 at four Swiss university
      hospitals, we analyzed 1602 patients who survived one year after recruitment.
      Targets based on the previous guidelines approach was defined as (1) achievement
      of LDL-C target < 1.8 mmol/l, (2) reduction of LDL-C >= 50% or (3)
      intensification of statin in patients who did not reach LDL-C targets. Targets
      based on the 2013 AHA/ACC guidelines approach was defined as the maximization of
      statin therapy at high-intensity in patients aged <=75 years and moderate- or
      high-intensity statin in patients >75 years. RESULTS: 1578 (99%) patients were
      prescribed statin at discharge, with 1120 (70%) at high-intensity. 1507 patients
      (94%) reported taking statin at one year, with 909 (57%) at high-intensity. Among
      482 patients discharged with sub-maximal statin, intensification of statin was
      only observed in 109 patients (23%). 773 (47%) patients reached the previous LDL
      C targets, while 1014 (63%) reached the 2013 AHA/ACC guidelines targetsone year
      after ACS (p value < 0.001). CONCLUSION: The application of the new 2013 AHA/ACC
      guidelines criteria would substantially increase the proportion of patients
      achieving recommended lipid targets one year after ACS. Clinical trial number,
      NCT01075868.

PMID- 25585032
TI  - Synaptic proteins in the hippocampus indicative of increased neuronal activity in
      CA3 in schizophrenia.
AB  - OBJECTIVE: In schizophrenia, hippocampal perfusion is increased and declarative
      memory function is degraded. Based on an a priori model of hippocampal
      dysfunction in schizophrenic psychosis, the authors postulated molecular and
      cellular changes in CA3 consistent with increased NMDA receptor signaling.
      METHOD: Postmortem hippocampal subfield tissue (CA3, CA1) from subjects with
      schizophrenia and nonpsychiatric comparison subjects was analyzed using Western
      blotting and Golgi histochemistry to examine the hypothesized outcomes. RESULTS:
      The GluN2B-containing NMDA receptors (GluN2B/GluN1) and their associated
      postsynaptic membrane protein PSD95 were both increased in schizophrenia in CA3
      tissue, but not in CA1 tissue. Quantitative analyses of Golgi-stained hippocampal
      neurons showed an increase in spine density on CA3 pyramidal cell apical
      dendrites (stratum radiatum) and an increase in the number of thorny
      excrescences. CONCLUSIONS: The hippocampal data are consistent with increased
      excitatory signaling in CA3 and/or with an elevation in silent synapses in CA3, a
      state that may contribute to an increase in long-term potentiation in CA3 with
      subsequent stimulation and "unsilencing." These changes are plausibly associated
      with increased associational activity in CA3, with degraded declarative memory
      function, and with formation of false memories with psychotic content. The
      influence of these hyperactive hippocampal projections on targets in the limbic
      neocortex could contribute to components of schizophrenia manifestations in other
      cerebral regions.

PMID- 25585033
TI  - Neuropsychiatric symptoms as predictors of progression to severe Alzheimer's
      dementia and death: the Cache County Dementia Progression Study.
AB  - OBJECTIVE: Little is known about factors influencing the rate of progression of
      Alzheimer's dementia. Using data from the Cache County Dementia Progression
      Study, the authors examined the link between clinically significant
      neuropsychiatric symptoms in mild Alzheimer's dementia and progression to severe
      dementia or death. METHOD: The Cache County Dementia Progression Study is a
      longitudinal study of dementia progression in incident cases of this condition.
      Survival analyses included unadjusted Kaplan-Meier plots and multivariate Cox
      proportional hazard models. Hazard ratio estimates controlled for age at dementia
      onset, dementia duration at baseline, gender, education level, General Medical
      Health Rating, and apolipoprotein E epsilon 4 genotype. RESULTS: Three hundred
      thirty-five patients with incident Alzheimer's dementia were studied. Sixty-eight
      (20%) developed severe dementia over the follow-up period. Psychosis (hazard
      ratio=2.007), agitation/aggression (hazard ratio=2.946), and any one clinically
      significant neuropsychiatric symptom (domain score >=4, hazard ratio=2.682) were
      associated with more rapid progression to severe dementia. Psychosis (hazard
      ratio=1.537), affective symptoms (hazard ratio=1.510), agitation/aggression
      (hazard ratio=1.942), mildly symptomatic neuropsychiatric symptoms (domain score
      of 1-3, hazard ratio=1.448), and clinically significant neuropsychiatric symptoms
      (hazard ratio=1.951) were associated with earlier death. CONCLUSIONS: Specific
      neuropsychiatric symptoms are associated with shorter survival time from mild
      Alzheimer's dementia to severe dementia and/or death. The treatment of specific
      neuropsychiatric symptoms in mild Alzheimer's dementia should be examined for its
      potential to delay time to severe dementia or death.

PMID- 25585034
TI  - Cortical morphology in 6- to 10-year old children with autistic traits: a
      population-based neuroimaging study.
AB  - OBJECTIVE: Recent evidence suggests that symptoms of social impairment in autism
      spectrum disorder (ASD) form a spectrum that extends into the general population.
      However, it is unclear whether the neuroanatomy of ASD also shows a similar
      continuum in the general population. Therefore, the goal of the present study was
      to investigate the relationship between cortical morphology and autistic traits
      along a continuum in a large population-based sample of young children. METHOD:
      The study included 717 children, aged 6-10 years, who are participants in the
      Generation R Study, a large population-based cohort. Autistic traits were
      measured using the Social Responsiveness Scale when the children were
      approximately 6 years old. High-resolution MRI was obtained, and morphological
      measures of the cortex, including cortical thickness and gyrification, were
      quantified brain-wide. RESULTS: Children with more autistic traits showed
      widespread areas of decreased gyrification. After excluding children with the
      highest autistic traits and confirmed ASD, the association remained present in a
      large cluster involving the left hemisphere temporal and precuneus regions.
      Comparable, but nonsignificant, effects when comparing a small sample of
      confirmed ASD case subjects with age- and gender-matched control subjects were
      observed. CONCLUSIONS: Differences in cortical morphology related to autistic
      traits along a continuum in a large population-based sample of school-aged
      children were found. Part of these differences remained after excluding the most
      severely affected children. These findings lend support to an extension of the
      neurobiology of autistic traits to the general population.

PMID- 25585036
TI  - Nocturnal enuresis: non-pharmacological treatments.
AB  - INTRODUCTION: Nocturnal enuresis affects 15% to 20% of 5-year-old children, 5% of
      10-year-old children, and 1% to 2% of people aged 15 years and older. Without
      treatment, 15% of affected children will become dry each year. Nocturnal enuresis
      is not diagnosed in children younger than 5 years, and treatment may be
      inappropriate for children younger than 7 years. METHODS AND OUTCOMES: We
      conducted a systematic review and aimed to answer the following clinical
      question: What are the effects of non-pharmacological interventions for relief of
      symptoms of nocturnal enuresis? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to October 2013 (Clinical Evidence
      reviews are updated periodically, please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA), the European
      Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory
      Agency (MHRA). RESULTS: We found five studies that met our inclusion criteria. We
      performed a GRADE evaluation of the quality of evidence for interventions.
      CONCLUSIONS: In this systematic review, we present information relating to the
      effectiveness and safety of the following interventions: acupuncture, dry bed
      training, enuresis alarm, and hypnotherapy.

PMID- 25585035
TI  - Ovarian hormone fluctuation, neurosteroids, and HPA axis dysregulation in
      perimenopausal depression: a novel heuristic model.
AB  - OBJECTIVE: In this conceptual review, the authors propose a novel mechanistic
      candidate in the etiology of depression with onset in the menopause transition
      ("perimenopausal depression") involving alterations in stress-responsive
      pathways, induced by ovarian hormone fluctuation. METHOD: The relevant literature
      in perimenopausal depression, including prevalence, predictors, and treatment
      with estrogen therapy, was reviewed. Subsequently, the growing evidence from
      animal models and clinical research in other reproductive mood disorders was
      synthesized to describe a heuristic model of perimenopausal depression
      development. RESULTS: The rate of major depressive disorder and clinically
      meaningful elevations in depressive symptoms increases two- to threefold during
      the menopause transition. While the mechanisms by which ovarian hormone
      fluctuation might impact mood are poorly understood, growing evidence from basic
      and clinical research suggests that fluctuations in ovarian hormones and derived
      neurosteroids result in alterations in regulation of the HPA axis by gamma
      aminobutyric acid (GABA). The authors' heuristic model suggests that for some
      women, failure of the GABAA receptor to regulate overall GABA-ergic tone in the
      face of shifting levels of these neurosteroids may induce HPA axis dysfunction,
      thereby increasing sensitivity to stress and generating greater vulnerability to
      depression. CONCLUSIONS: The proposed model provides a basis for understanding
      the mechanisms by which the changing hormonal environment of the menopause
      transition may interact with the psychosocial environment of midlife to
      contribute to perimenopausal depression risk. Future research investigating this
      model may inform the development of novel pharmacological treatments for
      perimenopausal depression and related disorders, such as postpartum depression
      and premenstrual dysphoric disorder.

PMID- 25585037
TI  - Chloride cotransporter NKCC1 inhibitor bumetanide protects against white matter
      injury in a rodent model of periventricular leukomalacia.
AB  - BACKGROUND: Periventricular leukomalacia (PVL) is a major form of preterm brain
      injury. Na(+)-K(+)-Cl(-) 1 cotransporter (NKCC1) expression on neurons and
      astrocytes is developmentally regulated and mediates Cl(-) reversal potential. We
      hypothesized that NKCC1 is highly expressed on oligodendrocytes (OLs) and
      increases vulnerability to hypoxia-ischemia (HI) mediated white matter injury,
      and that the NKCC1 inhibitor bumetanide would be protective in a rodent PVL
      model. METHODS: Immunohistochemistry in Long-Evans rats and PLP-EGFP transgenic
      mice was used to establish cell-specific expression of NKCC1 in the immature
      rodent brain. HI was induced on postnatal day 6 (P6) in rats and the protective
      efficacy of bumetanide (0.3 mg/kg/i.p. q12h * 60 h) established. RESULTS: NKCC1
      was expressed on OLs and subplate neurons through the first 2 postnatal weeks,
      peaking in white matter and the subplate between P3-7. Following HI, NKCC1 is
      expressed on OLs and neurons. Bumetanide treatment significantly attenuates
      myelin basic protein loss and neuronal degeneration 7 d post-HI. CONCLUSION:
      Presence and relative overexpression of NKCC1 in rodent cerebral cortex coincides
      with a period of developmental vulnerability to HI white matter injury in the
      immature prenatal brain. The protective efficacy of bumetanide in this model of
      preterm brain injury suggests that Cl(-) transport is a factor in PVL and that
      its inhibition may have clinical application in premature human infants.

PMID- 25585039
TI  - Nanocrystals for luminescent solar concentrators.
AB  - Luminescent solar concentrators (LSCs) harvest sunlight over large areas and
      concentrate this energy onto photovoltaics or for other uses by transporting
      photons through macroscopic waveguides. Although attractive for lowering solar
      energy costs, LSCs remain severely limited by luminophore reabsorption losses.
      Here, we report a quantitative comparison of four types of nanocrystal (NC)
      phosphors recently proposed to minimize reabsorption in large-scale LSCs: two
      nanocrystal heterostructures and two doped nanocrystals. Experimental and
      numerical analyses both show that even the small core absorption of the leading
      NC heterostructures causes major reabsorption losses at relatively short
      transport lengths. Doped NCs outperform the heterostructures substantially in
      this critical property. A new LSC phosphor is introduced, nanocrystalline Cd(1
      x)Cu(x)Se, that outperforms all other leading NCs by a significant margin in both
      small- and large-scale LSCs under full-spectrum conditions.

PMID- 25585038
TI  - Preliminary study on pathogenesis of bronchial asthma in children.
AB  - BACKGROUND: The etiology and pathogenesis of bronchial asthma remain unclear.
      This study is to investigate the risk factors related to bronchial asthma onset
      in children from genetics and immunology and preliminarily reveal the
      pathogenesis of bronchial asthma in children. METHODS: Real-time quantitative PCR
      was adopted to detect the expression level of TRPV1 gene and mRNA and enzyme
      linked immunosorbent assay method to the total immunoglobulin E level and levels
      of IL-4, IL-5, and IFN-gamma in serum in peripheral venous blood for children in
      two groups. Logistic regression analysis was applied to analyze the most
      essential factors inducing bronchial asthma in children. RESULTS: The mRNA level
      of TRPV1 in peripheral blood in the case group was higher than that in the
      control group (P < 0.01). The levels of IL-4, IL-5, and eosinophils in serum in
      the case group were markedly higher than those in the control group (P < 0.01),
      while IFN-gamma level in the case group was lower than that in the control group
      (P < 0.01). The results of logistic regression analysis indicated that TRPV1
      expression level, IL-4 level, and rs4790522 site mutation were the main risk
      factors inducing bronchial asthma in children. CONCLUSION: The levels of TRPV1
      gene expression and Th1/Th2 cytokines have a close relationship with asthma onset
      in children, which provides theoretical evidences for molecular targeted
      treatment in children with bronchial asthma.

PMID- 25585040
TI  - Delayed fluorescence in a solution-processable pure red molecular organic emitter
      based on dithienylbenzothiadiazole: a joint optical, electroluminescence, and
      magnetoelectroluminescence study.
AB  - The discovery of triplet excitons participating in the photoluminescent processes
      in a growing number of pure organic emitters represents an exciting impetus for a
      diversity of promising opto, bio, and optoelectronic applications. In this
      contribution, we have studied a small-molecule dithienylbenzothiadiazole-based
      red-emitting dye red-1b, which shows clearly delayed fluorescence under optical
      and electrical excitation. The OLED device that contained red-1b as a nondoped
      solution-processable emitter exhibited a moderately high utilization of exciton
      amounting to ~31% and slow efficiency roll-off. Magnetoelectroluminescence
      measurements revealed the coexistence of reverse intersystem crossing from the
      lowest triplet state to singlet state (RISC, E-type triplet to singlet up
      conversion) and triplet-triplet annihilation (TTA, P-type triplet to singlet up
      conversion). Specifically, in low current-density regime, the moderately high
      exciton utilization is attributed to RISC (i.e., thermally activated delayed
      fluorescence, TADF), whereas in high current-density regime, TTA may contribute
      to suppressing efficiency roll-off. Furthermore, the results showed that red-1b
      may represent a new kind of organic red emitters that display delayed
      fluorescence in a way differing from the few red emitters investigated so far. 

PMID- 25585041
TI  - Branched micelles by living crystallization-driven block copolymer self-assembly
      under kinetic control.
AB  - We have found that the width and shape (from rectangular to elliptical, to almost
      circular in cross-section) of the crystalline core of fiberlike micelles of
      polyferrocenyldimethylsilane (PFDMS) diblock copolymers can be varied by altering
      the degree of polymerization of PFDMS, and also the chemistry of the
      complementary corona-forming block. This enabled detailed studies of living
      crystallization-driven self-assembly (CDSA) processes that involved the addition
      of unimers with a short, crystallizable core-forming PFDMS block to a seed
      solution of short micelles with a large diameter crystalline core, derived from
      block copolymers with a longer PFDMS block. The morphology of resultant micelles
      was found to be highly dependent on the polarity of the solvent and temperature.
      For example, linear micelles were formed in less polar solvents (which are
      moderately poor solvents for PFDMS) and/or at higher temperatures. In contrast,
      the formation of branched structures could be "switched on" when the opposite
      conditions were used. Thus, the use of more polar solvents (which are very poor
      solvents for PFDMS) and ambient or subambient temperatures allowed the formation
      of branched micelles and block comicelles with variable and spatially distinct
      corona chemistries, including amphiphilic nanostructures. Rapid crystallization
      of added unimers at the seed micelle termini under nonequilibrium self-assembly
      conditions appears to facilitate the formation of the branched micellar
      structures as a kinetically trapped morphology. This is evidenced by the
      transformation of the branched micelles into linear micelles on heating at
      elevated temperatures. 

PMID- 25585042
TI  - Reciprocal inhibition between sensory ASH and ASI neurons modulates nociception
      and avoidance in Caenorhabditis elegans.
AB  - Sensory modulation is essential for animal sensations, behaviours and survival.
      Peripheral modulations of nociceptive sensations and aversive behaviours are
      poorly understood. Here we identify a biased cross-inhibitory neural circuit
      between ASH and ASI sensory neurons. This inhibition is essential to drive normal
      adaptive avoidance of a CuSO4 (Cu(2+)) challenge in Caenorhabditis elegans. In
      the circuit, ASHs respond to Cu(2+) robustly and suppress ASIs via electro
      synaptically exciting octopaminergic RIC interneurons, which release octopamine
      (OA), and neuroendocrinally inhibit ASI by acting on the SER-3 receptor. In
      addition, ASIs sense Cu(2+) and permit a rapid onset of Cu(2+)-evoked responses
      in Cu(2+)-sensitive ADF neurons via neuropeptides possibly, to inhibit ASHs. ADFs
      function as interneurons to mediate ASI inhibition of ASHs by releasing serotonin
      (5-HT) that binds with the SER-5 receptor on ASHs. This elaborate modulation
      among sensory neurons via reciprocal inhibition fine-tunes the nociception and
      avoidance behaviour. 

PMID- 25585043
TI  - Re-editing the paradigm of Cytidine (C) to Uridine (U) RNA editing.
AB  - Cytidine (C) to Uridine (U) RNA editing is a post-trancriptional modification
      that until recently was known to only affect Apolipoprotein b (Apob) RNA and
      minimally require 2 components of the C to U editosome, the deaminase APOBEC1 and
      the RNA-binding protein A1CF. Our latest work has identified a novel RNA-binding
      protein, RBM47, as a core component of the editosome, which can substitute A1CF
      for the editing of ApoB mRNA. In addition, new RNA species that are subjected to
      C to U editing have been identified. Here, we highlight these recent discoveries
      and discuss how they change our view of the composition of the C to U editing
      machinery and expand our knowledge of the functional attributes of C to U RNA
      editing. 

PMID- 25585044
TI  - X-DNA origami-networked core-supported lipid stratum.
AB  - DNA hydrogels are promising materials for various fields of research, such as in
      vitro protein production, drug carrier systems, and cell transplantation. For
      effective application and further utilization of DNA hydrogels, highly effective
      methods of nano- and microscale DNA hydrogel fabrication are needed. In this
      respect, the fundamental advantages of a core-shell structure can provide a
      simple remedy. An isolated reaction chamber and massive production platform can
      be provided by a core-shell structure, and lipids are one of the best shell
      precursor candidates because of their intrinsic biocompatibility and potential
      for easy modification. Here, we demonstrate a novel core-shell nanostructure made
      of gene-knitted X-shaped DNA (X-DNA) origami-networked gel core-supported lipid
      strata. It was simply organized by cross-linking DNA molecules via T4 enzymatic
      ligation and enclosing them in lipid strata. As a condensed core structure, the
      DNA gel shows Brownian behavior in a confined area. It has been speculated that
      they could, in the future, be utilized for in vitro protein synthesis, gene
      integration transporters, and even new molecular bottom-up biological
      machineries. 

PMID- 25585045
TI  - Prognosis-related factors in intensive care unit (ICU) patients with
      hematological malignancies: A retrospective cohort analysis in a Chinese
      population.
AB  - OBJECTIVES: This study investigates the link between patient characteristics and
      mortality in patients with hematological malignancies (HM) in three university
      affiliated hospitals in Hunan, China. METHODS: We conducted a detailed
      retrospective chart review of 121 sequential intensive care unit (ICU) admissions
      with HM over a 5-year period. Outcome measures were short- and long-term
      mortality rates and were correlated with physiologic and therapeutic factors. We
      also evaluate the performance of two severity-of-illness scoring systems in this
      population, particularly the value and trend of the sequential organ failure
      assessment (SOFA). RESULTS: The rates for ICU, 1-month and 6-month mortalities
      were 60.3, 85.9, and 90.9%, respectively. Invasive mechanical ventilation (IMV)
      was associated with worse outcomes at all time points. Both acute physiology and
      chronic health evaluation and SOFA scores had positive correlation with ICU
      mortality. An increase or no change in SOFA over the course of the admission or
      during the first 48 hours after admission was the most powerful adverse
      predictor. IMV use and renal dysfunction had a negative effect on the 1-month
      survival. CONCLUSION: Patients with HM have less access to intensive care
      resources in Hunan, China. The use of IMV, APACHII at admission, and SOFA trend
      have a strong predictive value in this population. Based on our results, we
      propose a panel of parameters for use when considering ICU transfer to guide
      patient management.

PMID- 25585046
TI  - Frequency of exogenous hormone therapy impacts spermiation in male Fowler's toad
      (Bufo fowleri).
AB  - Amphibians are experiencing a global extinction crisis and captive assurance
      colonies, along with reintroduction programs, are necessary to prevent further
      losses. Assisted reproductive technologies (ART), such as hormone-stimulated
      gamete collection and in vitro fertlisation (IVF), are conservation methods that
      can be used to increase reproductive output for breeding and reintroduction
      programs when animals fail to breed naturally. In order to maximise the
      production of offspring using ART, it is important to establish the physiological
      limitations on the frequency that hormone therapy can be used to collect gametes
      for IVF or assisted breeding. The present study examined the effects of the
      frequency of hormone-induced spermiation on sperm quantity and quality in
      Fowler's toad (Bufo fowleri) by comparing four levels of hormone injection
      frequencies: twice a week, once a week, every other week, and every 3 weeks.
      Sperm release was induced with an intraperitoneal injection of 300IU human
      chorionic gonadotropin (hCG). Spermatozoa were collected at three time points
      after injection (5, 7 and 9h) and sperm concentration, motility and quality of
      forward progressive movement were measured. A significant decrease in sperm
      concentration (P<0.01) was observed with the most frequent treatment (twice a
      week hormone injections). However, there was no negative effect of the treatments
      on sperm motility (P=0.06) or forward movement (P=0.06). We also observed a
      significant decrease in the concentration (P<0.01), motility (P=0.02) and quality
      of forward progressive movement (P=0.01) of spermatozoa at the 9h collection
      compared with earlier collection times. These results have clear implications for
      amphibian captive breeding programs, where more frequent hormone-induced
      spermiation could have a negative effect on male performance. We recommend that
      hormone injections be spaced a minimum of 2 weeks apart to optimise the health of
      the animals, assisted breeding, IVF or collection of gametes for genome resource
      banking.

PMID- 25585047
TI  - Making the circumcision controversy controversial: going meta and taking aim at
      the messenger(s): reply to Wamai et al.

PMID- 25585048
TI  - Copper-catalyzed oxidative alkenylation of thioethers via Csp(3)-H
      functionalization.
AB  - A novel copper-catalyzed oxidative alkenylation of thioethers via Csp(3)-H
      functionalization to construct allylic thioethers is first demonstrated.
      Different 1,1-disubstituted olefins could cross-couple with thioethers to
      generate the corresponding alkenylation products in moderate to excellent yields.
      This reaction is supposed to proceed via a radical process. 

PMID- 25585050
TI  - Improving personality/character traits in individuals with alcohol dependence:
      the influence of mindfulness-oriented meditation.
AB  - The study of personality is critical to enhance current knowledge of the
      psychological characteristics of alcohol dependence. Recent evidence shows that
      mindfulness-oriented meditation positively influences healthy individuals'
      character. Here, it was assessed whether 8-week mindfulness-oriented meditation
      promotes similar changes in a group of alcohol-dependent individuals. A control
      group with alcohol dependence was also tested. Mindfulness-oriented meditation
      participants showed an increase in the character scores of the temperament and
      character inventory together with reduced risks of relapse. These longitudinal
      data highlight the importance of assessing personality in alcohol-dependent
      individuals and support the utility of therapeutic interventions for alcohol
      dependence aimed at enhancing individuals' character. 

PMID- 25585049
TI  - Psychological symptoms among 2032 youth living with HIV: a multisite study.
AB  - This study determined the prevalence and patterns of psychological symptoms in
      adolescents and young adults living with HIV (YLWH) in medical care and
      relationships between psychological symptoms, route and duration of infection,
      and antiretroviral treatment (ART). A clinic-based sample of 2032 YLWH (mean age
      20.3 years), recruited from 20 adolescent medicine HIV clinics, completed a cross
      sectional survey of health behaviors and psychological symptoms using the Brief
      Symptom Inventory (BSI). Overall, 17.5% of youth reported psychological symptoms
      greater than the normative threshold on the Global Severity Index. A wide variety
      of symptoms were reported. The prevalence of clinical symptoms was significantly
      greater in youth with behaviorally acquired HIV compared to those with
      perinatally acquired infection (20.6% vs. 10.8%, OR=2.06 in Multiple Logistic
      Regression (MLR)), and in those not taking ART that had been prescribed (29. 2%
      vs. 18.8%, OR=1.68 in MLR). Knowing one's HIV status for more than one year and
      disclosure of HIV status were not associated with fewer symptoms. A large
      proportion of YLWH have psychological symptoms and the prevalence is greatest
      among those with behaviorally acquired infection. The high rate of psychological
      symptoms for youth not taking ART that is prescribed is a cause for concern.
      Symptoms do not appear to be a transient reaction to diagnosis of HIV.

PMID- 25585052
TI  - Identification of the Vascular Source of Vasogenic Brain Edema following
      Traumatic Brain Injury Using In Vivo 2-Photon Microscopy in Mice.
AB  - Vasogenic brain edema due to vascular leakage is one of the most important
      factors determining the clinical outcome of patients following acute brain
      injury. To date, performing a detailed in vivo quantification of vascular leakage
      has not been possible. Here, we used in vivo 2-photon microscopy (2-PM) to
      determine the spatial (3D) and temporal development of vasogenic brain edema
      following traumatic brain injury (TBI) in mice; in addition, we identified the
      vessel types involved in vascular leakage. Thirteen male Tie2-GFP mice (6-8 weeks
      old) were subjected to controlled cortical impact (CCI) or a sham operation;
      subsequently, a cranial window was prepared adjacent to the injury site, and
      tetramethylrhodamine-dextran (TMRM, 40 mg/kg, MW 40,000) was injected
      intravenously to visualize blood plasma leakage. Parenchymal fluorescence
      intensity was monitored in three regions for 2-4 h post-CCI, reaching from the
      surface of the brain to a depth of 300 MUm, and TMRM leakage was measured as an
      increase in TMRM fluorescence intensity outside the vessel lumen and in the
      parenchyma. In the CCI group, vascular leakage was detected in all investigated
      regions as early as 2.5 h post-injury. This leakage increased over time and was
      more pronounced proximal to the primary contusion. Both arterioles and venules
      contributed similarly to brain edema formation and their contribution was
      independent of vessel size; however, capillaries were the major contributor to
      leakage. In summary, using 2-PM to perform in vivo 3D deep-brain imaging, we
      found that TBI induces vascular leakage from capillaries, venules, and
      arterioles. Thus, all three vessel types are involved in trauma-induced brain
      edema and should be considered when developing novel therapies for preventing
      vasogenic brain edema. 

PMID- 25585051
TI  - Loss of Atg12, but not Atg5, in pro-opiomelanocortin neurons exacerbates diet
      induced obesity.
AB  - The autophagy-related proteins ATG12 and ATG5 form a covalent complex essential
      for autophagy. Here, we demonstrate that ATG12 has distinct functions from ATG5
      in pro-opiomelanocortin (POMC)-expressing neurons. Upon high-fat diet (HFD)
      consumption, mice lacking Atg12 in POMC-positive neurons exhibit accelerated
      weight gain, adiposity, and glucose intolerance, which is associated with
      increased food intake, reduced ambulation, and decreased LEP/leptin sensitivity.
      Importantly, although genetic deletion of either Atg12 or Atg5 renders POMC
      neurons autophagy-deficient, mice lacking Atg5 in POMC neurons do not exhibit
      these phenotypes. Hence, we propose nonautophagic functions for ATG12 in POMC
      neurons that counteract excessive weight gain in response to HFD consumption. 

PMID- 25585053
TI  - Impact of boronate capping groups on biological characteristics of novel
      (99m)Tc(III) complexes [(99m)TcCl(CDO)(CDOH)2B-R] (CDOH2 = cyclohexanedione
      dioxime).
AB  - This study sought to explore the impact of boronate groups on the heart uptake
      and myocardial retention of novel (99m)Tc(III) complexes [(99m)TcCl(CDO)(CDOH)2B
      R] ((99m)Tc-ISboroxime: R = isoxazol-4-yl (IS); (99m)Tc-MPboroxime: R = N
      methylpyridinium (MP); (99m)Tc-PAboroxime: R = pyrazol-3-yl (PA); (99m)Tc
      PYboroxime: R = pyridin-3-yl (PY); and (99m)Tc-5Uboroxime: R = uracil-5-yl (5U)).
      All five new (99m)Tc(III) radiotracers were prepared in high yield and high
      radiochemical purity (RCP = 90-98%), and they remained stable in the kit mixture
      for >6 h. Biodistribution and imaging (planar and SPECT) studies were carried out
      using Sprague-Dawley (SD) rats. Planar image quantification was performed to
      compare their myocardial retention and liver clearance kinetics. It was found
      that their heart retention and liver clearance curves were best fitted to the
      biexponential decay function. The initial heart uptake at 0-1 min after injection
      followed the general ranking order of (99m)Tc-ISboroxime (4.98 +/- 1.05%ID) ~
      (99m)Tc-Teboroxime (4.56 +/- 0.91%ID) ~ (99m)Tc-PAboroxime (4.03 +/- 1.23%ID) ~
      (99m)Tc-PYboroxime (4.07 +/- 0.80%ID) > (99m)Tc-5Uboroxime (3.24 +/- 0.67%ID) >
      (99m)Tc-MPboroxime (2.53 +/- 0.65%ID). The fast-phase myocardial retention time
      followed the general order of (99m)Tc-PAboroxime (3.21 +/- 0.29 min) > (99m)Tc
      Teboroxime (1.63 +/- 0.40 min) ~ (99m)Tc-PYboroxime (1.57 +/- 0.29 min) ~ (99m)Tc
      ISboroxime (1.55 +/- 0.32 min) > (99m)Tc-MPboroxime (0.68 +/- 0.16 min) > (99m)Tc
      5Uboroxime (0.33 +/- 0.11 min). (99m)Tc-PAboroxime (3.05 +/- 1.10%ID/g) and
      (99m)Tc-ISboroxime (3.75 +/- 0.68%ID/g) had the 2 min initial heart uptake very
      close to that of (99m)Tc-Teboroxime (3.30 +/- 0.50%ID/g). However, the myocardial
      retention time of (99m)Tc-PAboroxime was significantly longer than that of
      (99m)Tc-ISboroxime and (99m)Tc-Teboroxime. Even though the best time window is 0
      5 min for SPECT image acquisition, high quality SPECT images could be obtained
      during the first 30 min postinjection of (99m)Tc-PAboroxime in SD rats. This
      statement was supported by the SPECT/CT studies in normal pigs. On the basis of
      results from this study, it was concluded that boronate groups had significant
      impact on the heart uptake, myocardial retention, and liver clearance kinetics of
      (99m)Tc(III) complexes [(99m)TcCl(CDO)(CDOH)2B-R]. The combination of high
      initial heart uptake with longer myocardial retention makes it possible to image
      the heart with (99m)Tc-PAboroxime during the first 30 min using both standard and
      specialized cardiac SPECT cameras. 

PMID- 25585055
TI  - Evolving a Behavioral Repertoire for a Walking Robot.
AB  - Numerous algorithms have been proposed to allow legged robots to learn to walk.
      However, most of these algorithms are devised to learn walking in a straight
      line, which is not sufficient to accomplish any real-world mission. Here we
      introduce the Transferability-based Behavioral Repertoire Evolution algorithm
      (TBR-Evolution), a novel evolutionary algorithm that simultaneously discovers
      several hundreds of simple walking controllers, one for each possible direction.
      By taking advantage of solutions that are usually discarded by evolutionary
      processes, TBR-Evolution is substantially faster than independently evolving each
      controller. Our technique relies on two methods: (1) novelty search with local
      competition, which searches for both high-performing and diverse solutions, and
      (2) the transferability approach, which combines simulations and real tests to
      evolve controllers for a physical robot. We evaluate this new technique on a
      hexapod robot. Results show that with only a few dozen short experiments
      performed on the robot, the algorithm learns a repertoire of controllers that
      allows the robot to reach every point in its reachable space. Overall, TBR
      Evolution introduced a new kind of learning algorithm that simultaneously
      optimizes all the achievable behaviors of a robot. 

PMID- 25585054
TI  - Human embryonic stem cells form functional thyroid follicles.
AB  - OBJECTIVE: The molecular events that lead to human thyroid cell speciation remain
      incompletely characterized. It has been shown that overexpression of the
      regulatory transcription factors Pax8 and Nkx2-1 (ttf-1) directs murine embryonic
      stem (mES) cells to differentiate into thyroid follicular cells by initiating a
      transcriptional regulatory network. Such cells subsequently organized into three
      dimensional follicular structures in the presence of extracellular matrix. In the
      current study, human embryonic stem (hES) cells were studied with the aim of
      recapitulating this scenario and producing functional human thyroid cell lines.
      METHODS: Reporter gene tagged pEZ-lentiviral vectors were used to express human
      PAX8-eGFP and NKX2-1-mCherry in the H9 hES cell line followed by differentiation
      into thyroid cells directed by Activin A and thyrotropin (TSH). RESULTS: Both
      transcription factors were expressed efficiently in hES cells expressing either
      PAX8, NKX2-1, or in combination in the hES cells, which had low endogenous
      expression of these transcription factors. Further differentiation of the double
      transfected cells showed the expression of thyroid-specific genes, including
      thyroglobulin (TG), thyroid peroxidase (TPO), the sodium/iodide symporter (NIS),
      and the TSH receptor (TSHR) as assessed by reverse transcription polymerase chain
      reaction and immunostaining. Most notably, the Activin/TSH-induced
      differentiation approach resulted in thyroid follicle formation and abundant TG
      protein expression within the follicular lumens. On stimulation with TSH, these
      hES-derived follicles were also capable of dose-dependent cAMP generation and
      radioiodine uptake, indicating functional thyroid epithelial cells. CONCLUSION:
      The induced expression of PAX8 and NKX2-1 in hES cells was followed by
      differentiation into thyroid epithelial cells and their commitment to form
      functional three-dimensional neo-follicular structures. The data provide proof of
      principal that hES cells can be committed to thyroid cell speciation under
      appropriate conditions.

PMID- 25585056
TI  - Photocatalytic hydrogen evolution over beta-iron silicide under infrared-light
      irradiation.
AB  - We investigated the ability of beta-iron silicide (beta-FeSi2) to serve as a
      hydrogen (H2)-evolution photocatalyst due to the potential of its conduction band
      bottom, which may allow thermodynamically favorable H2 evolution in spite of its
      small band-gap of 0.80 eV. beta-FeSi2 had an apparent quantum efficiency for H2
      evolution of ~24% up to 950 nm (near infrared light), in the presence of the
      dithionic acid ion (S2O6(2-)) as a sacrificial agent. It was also sensitive to
      infrared light (>1300 nm) for H2 evolution. 

PMID- 25585057
TI  - The Three Lineages of the Diploid Hybrid Verticillium longisporum Differ in
      Virulence and Pathogenicity.
AB  - Verticillium longisporum is an economically important vascular pathogen of
      Brassicaceae crops in different parts of the world. V. longisporum is a diploid
      hybrid that consists of three different lineages, each of which originated from a
      separate hybridization event between two different sets of parental species. We
      used 20 isolates representing the three V. longisporum lineages and the relative
      V. dahliae, and performed pathogenicity tests on 11 different hosts, including
      artichoke, cabbage, cauliflower, cotton, eggplant, horseradish, lettuce, linseed,
      oilseed rape (canola), tomato, and watermelon. V. longisporum was overall more
      virulent on the Brassicaceae crops than V. dahliae, which was more virulent than
      V. longisporum across the non-Brassicaceae crops. There were differences in
      virulence between the three V. longisporum lineages. V. longisporum lineage A1/D1
      was the most virulent lineage on oilseed rape, and V. longisporum lineage A1/D2
      was the most virulent lineage on cabbage and horseradish. We also found that on
      the non-Brassicaceae hosts eggplant, tomato, lettuce, and watermelon, V.
      longisporum was more or equally virulent than V. dahliae. This suggests that V.
      longisporum may have a wider potential host range than currently appreciated. 

PMID- 25585058
TI  - Collections of Puccinia triticina in Different Provinces of China Are Highly
      Related for Virulence and Molecular Genotype.
AB  - Collections of Puccinia triticina, the wheat leaf rust pathogen, were obtained
      from seven provinces in China from 2009 and 2010. Single uredinial isolates were
      derived and tested for virulence phenotype to 20 lines of Thatcher wheat that
      differ for single leaf rust resistance genes, and for molecular genotype with 23
      simple sequence repeat (SSR) primers. Forty-eight virulence phenotypes were
      described among the 155 isolates tested for virulence. All but four isolates were
      virulent to Lr26, and no isolates with virulence to Lr18 or Lr24 were found. The
      three most common phenotypes, FCBQQ, PCGLN, and PCGLL, were found in five, five,
      and three provinces, respectively. Thirty-six SSR genotypes were found among the
      100 isolates tested for molecular variation. Isolates with identical virulence
      phenotypes and SSR genotypes were found in more than one province. Analysis of
      variation showed no overall differentiation of SSR genotypes or virulence
      phenotypes based on province of origin. The SSR genotypes had high levels of
      linkage disequilibrium, high levels of observed heterozygosity, and significant
      correlation with the virulence phenotypes, all measures that indicated clonal
      reproduction. Bayesian cluster analysis and principle component plots indicated
      three groups of SSR genotypes that also varied significantly for virulence. The
      seven provinces are continuously adjacent to each other and likely form a single
      epidemiological zone for P. triticina. 

PMID- 25585059
TI  - The Dynamics and Environmental Influence on Interactions Between Cassava Brown
      Streak Disease and the Whitefly, Bemisia tabaci.
AB  - Cassava brown streak disease (CBSD) is currently the most significant virus
      disease phenomenon affecting African agriculture. In this study, we report
      results from the most extensive set of field data so far presented for CBSD in
      Africa. From assessments of 515 farmers' plantings of cassava, incidence in the
      Coastal Zone of Tanzania (46.5% of plants; 87% of fields affected) was higher
      than in the Lake Zone (22%; 34%), but incidences for both zones were greater than
      previous published records. The whitefly vector, Bemisia tabaci, was more
      abundant in the Lake Zone than the Coastal Zone, the reverse of the situation
      reported previously, and increased B. tabaci abundance is driving CBSD spread in
      the Lake Zone. The altitudinal "ceiling" previously thought to restrict the
      occurrence of CBSD to regions <1,000 masl has been broken as a consequence of the
      greatly increased abundance of B. tabaci in mid-altitude areas. Among
      environmental variables analyzed, minimum temperature was the strongest
      determinant of CBSD incidence. B. tabaci in the Coastal and Lake Zones responded
      differently to environmental variables examined, highlighting the biological
      differences between B. tabaci genotypes occurring in these regions and the
      superior adaptation of B. tabaci in the Great Lakes region both to cassava and
      low temperature conditions. Regression analyses using multi-country data sets
      could be used to determine the potential environmental limits of CBSD. Approaches
      such as this offer potential for use in the development of predictive models for
      CBSD, which could strengthen country- and continent-level CBSD pandemic
      mitigation strategies. 

PMID- 25585060
TI  - Nanoparticle hardness controls the internalization pathway for drug delivery.
AB  - Nanoparticle (NP)-based drug delivery systems offer fundamental advantages over
      current therapeutic agents that commonly display a longer circulation time, lower
      toxicity, specific targeted release, and greater bioavailability. For successful
      NP-based drug delivery it is essential that the drug-carrying nanocarriers can be
      internalized by the target cells and transported to specific sites, and the
      inefficient internalization of nanocarriers is often one of the major sources for
      drug resistance. In this work, we use the dissipative particle dynamics
      simulation to investigate the effect of NP hardness on their internalization
      efficiency. Three simplified models of NP platforms for drug delivery, including
      polymeric NP, liposome and solid NP, are designed here to represent increasing
      nanocarrier hardness. Simulation results indicate that NP hardness controls the
      internalization pathway for drug delivery. Rigid NPs can enter the cell by a
      pathway of endocytosis, whereas for soft NPs the endocytosis process can be
      inhibited or frustrated due to wrapping-induced shape deformation and non-uniform
      ligand distribution. Instead, soft NPs tend to find one of three penetration
      pathways to enter the cell membrane via rearranging their hydrophobic and
      hydrophilic segments. Finally, we show that the interaction between nanocarriers
      and drug molecules is also essential for effective drug delivery. 

PMID- 25585061
TI  - Fluoroquinolone resistance in Neisseria gonorrhoeae after cessation of
      ciprofloxacin usage in San Francisco: using molecular typing to investigate
      strain turnover.
AB  - BACKGROUND: Ciprofloxacin resistance (CipR) among gonococcal strains in San
      Francisco (SF) increased between 2001 and 2006 and decreased between 2007 and
      2009. Molecular typing of isolates obtained from 2005 to 2009 was performed to
      elucidate changes in CipR prevalence. METHODS: A total of 2526 samples were
      collected at the SF City Clinic between 2001 and 2009. Minimum inhibitory
      concentrations to ciprofloxacin were obtained by agar dilution. Prevalences of
      CipR strains were determined, with corresponding confidence intervals (CIs).
      Between 2005 and 2009, 460 isolates were selected for molecular typing using
      Neisseria gonorrhoeae multiantigen sequence typing. RESULTS: Between 2001 and
      2006, the prevalence of CipR increased from 3.4% (95% CI, 1.3%-5.4%) to 44% (95%
      CI, 39%-50%). However, in 2007 prevalence began to decrease, reaching 9.6% (95%
      CI, 6.0%-13%) by 2009. Of the 203 strain types identified between 2005 and 2009,
      126 genogroups of closely related strain types were formed (varying by <=1% at
      both target loci). Levels of CipR within the data set correlate with the
      prevalence of 3 major genogroups (G): G437, G1407, and G3112. CONCLUSIONS:
      Molecular typing reveals that CipR within the tested population is maintained by
      strain turnover between resistant genogroups. Despite early recommendation in
      2002 to stop ciprofloxacin use in California, CipR in SF increased through 2006.
      The subsequent decrease in CipR corresponds with the 2007 national recommendation
      to cease ciprofloxacin treatment of gonorrhea, which suggests that national
      recommendations are potentially more effective at reducing CipR than regional
      recommendations in areas with high strain turnover.

PMID- 25585062
TI  - American Indians, substance use, and sexual behavior: do predictors of sexually
      transmitted infections explain the race gap among young adults?
AB  - BACKGROUND: In this study, we examined whether substance use and risky sexual
      behaviors predicted sexually transmitted infections (STIs) among American Indian
      (AI) and white young adults. Furthermore, we explored whether these factors
      explained the race disparity in STIs. METHODS: We conducted a cross-sectional
      analysis of wave 3 of the National Longitudinal Study of Adolescent Health
      collected in 2001 to 2002. Young adult participants (aged 18-26 years) provided
      urine specimens that were tested for chlamydia, gonorrhea, and trichomoniasis
      infection. Estimates of the association between AI with any STI were adjusted for
      sexual and other risk behavior correlates using multivariate regression
      techniques. RESULTS: Nine percent of AIs (n = 367) and 3.6% of whites (n = 7813)
      tested positive for an STI. Race differences were found for substance use
      (injection drug use, 3.1% AI vs. 1.3% white; alcohol use frequency, 2.01% AI vs.
      2.5% white; binge drinking frequency, 1.25% AI vs. 1.53% white). Among sexually
      active respondents, AIs were more likely to have paid for sex (9%) than whites
      (3%). After adjustment, early sexual initiation (adjusted odds ratio, 1.69; 95%
      confidence interval, 1.19-2.41), no condom use at last sex (adjusted odds ratio,
      1.47; 95% confidence interval, 1.08-2.01), and AI race (adjusted odds ratio,
      2.45; 95% confidence interval 1.46-4.11) were significantly associated with
      having an STI. CONCLUSIONS: Individual-level sexual and other risk behaviors do
      not fully explain disparities in STIs among AIs compared with white young adults.
      Further examination of network and community factors is needed to explain these
      disparities.

PMID- 25585063
TI  - Generalized lymphadenopathy and 18-fluorine fluorodeoxyglucose positron emission
      tomography/computed tomography: targeting diagnostic intervention, characterizing
      disease extent, and assessing treatment efficacy in syphilis.
AB  - 18-Fluorine fluorodeoxyglucose positron emission tomography/computed tomography
      (PET/CT) has been shown to have use in the diagnosis of inflammatory and
      infectious diseases in addition to its primary use in cancer. We describe a case
      of early neurosyphilis that initially presented as symmetric, generalized
      lymphadenopathy on PET/CT. We conclude that PET/CT may play a role in evaluating
      targeted diagnostic interventions, disease extent, and treatment efficacy for
      disseminated syphilis. 

PMID- 25585065
TI  - Male human papillomavirus vaccine acceptance is enhanced by a brief intervention
      that emphasizes both male-specific vaccine benefits and altruistic motives.
AB  - BACKGROUND: Although female human papillomavirus (HPV) vaccine acceptance has
      been widely studied, research on vaccine uptake among boys and men is needed.
      Male HPV vaccination can provide both individual and community-level benefit by
      offering recipients personal health protection while concurrently minimizing HPV
      transmission and ultimately providing female health protection. As such, male
      vaccine acceptance may be enhanced by emphasizing both altruistic motives (female
      health protection) and personal health benefits. METHODS: A university-based
      sample of young men completed computer-administered surveys and viewed
      informational interventions that varied in the inclusion or exclusion of
      altruistic motives and in the level of emphasis on male-specific HPV-related
      illnesses and vaccine benefits. Human papillomavirus vaccine acceptance was
      assessed immediately after intervention. RESULTS: Participants who received the
      intervention emphasizing both altruistic motives and male-specific information
      endorsed the greatest vaccine acceptance (mean [SD], 3.6 [1.0]). CONCLUSION:
      Provider and community-level interventions highlighting both altruistic motives
      and personal health vaccine benefits may enhance HPV vaccine uptake among young
      men.

PMID- 25585064
TI  - Correlates of human papillomavirus vaccine coverage: a state-level analysis.
AB  - BACKGROUND: We tested the hypothesis that states with higher rates of cancers
      associated with human papillomavirus (HPV) would have lower HPV vaccine coverage.
      METHODS: We gathered state-level data on HPV-related cancer rates and HPV vaccine
      initiation coverage for girls and boys, separately, and HPV vaccine follow
      through (i.e., receipt of 3 doses among those initiating the series) for girls
      only. In addition, we gathered state-level data on demographic composition and
      contact with the health care system. We calculated Pearson correlations for these
      ecological relationships. RESULTS: Human papillomavirus vaccine initiation among
      girls was lower in states with higher levels of cervical cancer incidence and
      mortality (r = -0.29 and -0.46, respectively). In addition, vaccine follow
      through among girls was lower in states with higher levels of cervical cancer
      mortality (r = -0.30). Other cancer rates were associated with HPV vaccine
      initiation and follow-through among girls, but not among boys. Human
      papillomavirus vaccine initiation among girls was lower in states with higher
      proportions of non-Hispanic black residents and lower proportions of higher
      income residents. Human papillomavirus vaccine follow-through was higher in
      states with greater levels of adolescents' contact with the health care system.
      CONCLUSIONS: Human papillomavirus vaccine coverage for girls was lower in states
      with higher HPV-related cancer rates. Public health efforts should concentrate on
      geographic areas with higher cancer rates. Strengthening adolescent preventive
      health care use may be particularly important to increase vaccine follow-through.
      Cost-effectiveness analyses may overestimate the benefits of current vaccination
      coverage and underestimate the benefits of increasing coverage.

PMID- 25585066
TI  - Substantial increases in chlamydia and gonorrhea positivity unexplained by
      changes in individual-level sexual behaviors among men who have sex with men in
      an Australian sexual health service from 2007 to 2013.
AB  - BACKGROUND: To determine the risk-adjusted temporal trend of gonorrhea and
      chlamydia positivity and associated risk behaviors among men who have sex with
      men (MSM) attending a sexual health clinic in Melbourne in Australia. METHODS:
      Gonorrhea and chlamydia positivity by anatomical site adjusted for year of test,
      age, number of sexual partners, and condom use among MSM attending Melbourne
      Sexual Health Centre from 2007 to 2013 were calculated using generalized
      estimating equation regression models. RESULTS: A total of 12,873 MSM were
      included with a median age of 30.0 years. The proportion with pharyngeal,
      urethral, and anal gonorrhea was 1.7%, 2.3%, and 2.9%, respectively. The adjusted
      odds of gonorrhea positivity increased by 9% (95% confidence interval [CI], 3%
      15%), 11% (95% CI, 6%-17%), and 12% (95% CI, 7%-17%) per year, respectively. The
      proportion of MSM who were infected with anal chlamydia was 5.6%, with an average
      increase of 6% (95% CI, 3%-10%) per year; however, no significant change was
      observed in urethral chlamydia positivity (adjusted odds ratio, 1.02; 95% CI,
      0.98-1.06). Increases in gonorrhea and chlamydia positivity were primarily
      restricted to MSM who reported more than 10 partners in 12 months. The number of
      partners in the last 12 months fell from 16.6 to 10.5, whereas consistent condom
      use with casual partners decreased from 64.6% to 58.9% over the study period.
      CONCLUSIONS: Gonorrhea and chlamydia have increased among MSM despite the
      decrease in the number of sexual partners and are occurring primarily in MSM with
      high numbers of partners and persist after adjusting for known risk factors,
      suggesting that unmeasured factors (e.g., more assortative mixing patterns) may
      explain the observed changes.

PMID- 25585067
TI  - Estimating HIV protective effects of method adherence with combinations of
      preexposure prophylaxis and condom use among African American men who have sex
      with men.
AB  - BACKGROUND: Prevention of sexually acquired HIV infection now includes both
      consistent condom use and daily use of oral antiretroviral preexposure
      prophylaxis (PrEP). Persons at substantial HIV risk can now use one or both
      prevention methods, but a combined HIV protective effect has not been assessed.
      METHODS: We use deterministic models to examine the impact of method adherence
      and rates of PrEP and male condom use on number of anticipated HIV infections.
      Analyses were based on hypothetical cohorts of 10,000 African American men who
      have sex with men (AAMSM), a population with the highest HIV incidence in the
      United States. Parameters used in the model (condom effectiveness, PrEP
      effectiveness, HIV incidence) were based on published findings. RESULTS: Among
      AAMSM who never use PrEP, an estimated 323 annual HIV infections would occur
      among those who always use condoms, 1007 among sometimes condom users, and 1094
      among never condoms users. Among AAMSM who never (or inconsistently) use condoms,
      295 (272) infections would occur among those who report at least 90% PrEP
      adherence and 744 (684) infection occur with less than 50% adherence. Among AAMSM
      who are consistently (or sometimes) taking PrEP, the highest protection is seen
      with consistent condom use, 87 (220) HIV infections and 92.0% (79.9%) prevention
      effectiveness. DISCUSSION: Among AAMSM with inconsistent or never condom use, the
      addition of PrEP at either modest or high adherence can increase HIV protection.
      For consistent condom users, any PrEP use can increase HIV protection. These
      analyses provide an approach for rethinking HIV risk management by calculating
      combined HIV protective effects of using one or more effective prevention
      methods.

PMID- 25585070
TI  - Preexposure prophylaxis to prevent bacterial sexually transmitted infections in
      men who have sex with men.

PMID- 25585069
TI  - Doxycycline prophylaxis to reduce incident syphilis among HIV-infected men who
      have sex with men who continue to engage in high-risk sex: a randomized,
      controlled pilot study.
AB  - BACKGROUND: Incident syphilis infections continue to be especially prevalent
      among a core group of HIV-infected men who have sex with men (MSM). Because of
      synergy between syphilis and HIV infections, innovative means for controlling
      incident syphilis infections are needed. METHODS: Thirty MSM who had syphilis
      twice or more since their HIV diagnosis were randomized to receive either daily
      doxycycline prophylaxis or contingency management (CM) with incentive payments
      for remaining free of sexually transmitted diseases (STDs). Participants were
      tested for the bacterial STDs gonorrhea (Neisseria gonorrhoeae), chlamydia
      (Chlamydia trachomatis) and syphilis at weeks 12, 24, 36, and 48 and completed a
      behavioral risk questionnaire during each visit to assess number of partners,
      condom use, and drug use since the last visit. Generalized linear mixed models
      were used to analyze differences between arms in STD incidence and risk behaviors
      at follow-up. RESULTS: Doxycycline arm participants were significantly less
      likely to test positive for any selected bacterial STD during 48 weeks of follow
      up (odds ratio, 0.27; confidence interval, 0.09-0.83) compared with CM arm
      participants (P = 0.02).There were no significant self-reported risk behavior
      differences between the doxycycline and CM arms at follow-up. CONCLUSIONS: Daily
      doxycycline taken prophylactically was associated with a decreased incidence of
      N. gonorrhoeae, C. trachomatis, or syphilis incident infections among a core
      group of HIV-infected MSM at high risk for these infections. Safe and effective
      biomedical tools should be included in the efforts to control transmission of
      syphilis, especially in this population. A randomized clinical trial should be
      conducted to confirm and extend these findings.

PMID- 25585068
TI  - A longitudinal study of human papillomavirus 16 L1, e6, and e7 seropositivity and
      oral human papillomavirus 16 infection.
AB  - BACKGROUND: Individuals with human papillomavirus (HPV) infections can develop
      IgG antibodies to HPV proteins including the L1 capsid and E6 and E7
      oncoproteins. Evidence on whether L1 antibodies reduce the risk of cervical HPV
      infection is mixed, but this has not been explored for oral HPV infections.
      Antibodies to HPV16's E6 oncoprotein have been detected in some oropharyngeal
      cancer cases years before cancer diagnosis, but it is unknown if these antibodies
      are associated with oral HPV16 DNA. METHODS: Enzyme-linked immunosorbent assays
      tested for serum antibodies to HPV16's L1 capsid in 463 HIV-infected and 293 HIV
      uninfected adults, and for antibodies to recombinantly expressed E6 and E7
      oncoproteins to HPV16 in 195 HIV-infected and 69 HIV-uninfected cancer-free
      participants at baseline. Oral rinse samples were collected semiannually for up
      to 3 years and tested for HPV DNA using PGMY 09/11 primers. Adjusted Poisson,
      logistic, and Wei-Lin-Weissfeld regression models were used. RESULTS: Human
      papillomavirus 16 L1 seroreactivity did not reduce the subsequent risk of
      incident oral HPV16 infection in unadjusted (hazard ratio, 1.4; 95% confidence
      interval, 0.59-3.3) or adjusted (adjusted hazard ratio = 1.1; 95% confidence
      interval, 0.41-3.0) analysis. Antibodies to HPV16 E6 and E7 oncoproteins were
      detected in 7.6% and 3.4% of participants, respectively, but they were not
      associated with baseline oral HPV16 DNA prevalence or oral HPV16 persistence
      (each P > 0.40). CONCLUSIONS: Naturally acquired HPV16 L1 antibodies did not
      reduce the risk of subsequent oral HPV16 infection. Human papillomavirus 16 E6
      and E7 seropositivity was not a marker for oral HPV16 infection in this
      population without HPV-related cancer.

PMID- 25585071
TI  - Simulating watch and wait for rectal cancer.

PMID- 25585072
TI  - Do we have any real understanding of what is happening in rectal cancer care?

PMID- 25585073
TI  - Avoiding radical surgery improves early survival in elderly patients with rectal
      cancer, demonstrating complete clinical response after neoadjuvant therapy:
      results of a decision-analytic model.
AB  - BACKGROUND: In elderly and comorbid patients with rectal cancer, radical surgery
      is associated with significant perioperative mortality. Data suggest that a watch
      and-wait approach where a complete clinical response is obtained after
      neoadjuvant chemoradiotherapy might be oncologically safe. OBJECTIVE: This study
      aimed to determine whether patient age and comorbidity should influence surgeon
      and patient decision making where a complete clinical response is obtained.
      DESIGN: Decision-analytic modeling consisting of a decision tree and Markov chain
      simulation was used. Modeled outcome parameters were elicited both from
      comprehensive literature review and from a national patient outcomes database.
      SETTINGS: Outcomes for 3 patient cohorts treated with neoadjuvant therapy were
      modeled after either surgery or watch and wait. PATIENTS: Patients included 60
      year-old and 80-year-old men with mild comorbidities (Charlson score <3) and 80
      year-old men with significant comorbidities (Charlson score >3). MAIN OUTCOME
      MEASURES: Absolute survival, disease-free survival, and quality-adjusted life
      years were measured. RESULTS: The model found that absolute survival was similar
      in 60-year-old patients but was significantly improved in fit and comorbid 80
      year-old patients at 1 year after treatment where watch and wait was implemented
      instead of radical surgery, with a survival advantage of 10.1% (95% CI, 7.9-12.6)
      and 13.5% (95% CI, 10.2-16.9). At all of the other time points, absolute survival
      was equivalent for both techniques. There were no short- or long-term differences
      among any patient groups managed either by radical surgery or watch and wait in
      terms of either disease-free survival or quality-adjusted life years.
      LIMITATIONS: Oncologic data for the watch-and-wait approach used for this study
      is derived from only a small number of studies pertaining to a highly selected
      group of patients. The 90-day postoperative mortality rate derived from the
      United Kingdom population-based study might be lower in other countries or
      individual institutions. CONCLUSIONS: This study suggests competing effects of
      oncologic and surgical risk when using watch-and-wait management and that elderly
      and comorbid patients have the most to gain from this approach.

PMID- 25585074
TI  - Local excision for early stage rectal cancer in patients over age 65 years: 2000
      2009.
AB  - BACKGROUND: Local excision of rectal cancer is an attractive option because it
      avoids the morbidity of radical resection. Concerns have arisen during the past
      decade, however, regarding substandard oncologic results. OBJECTIVE: Using the
      most recent Survey of Epidemiology and End Results-Medicare data, we examined the
      change in the use of local excision for rectal cancer from 2000 to 2009 and
      examined patient, surgeon, and hospital factors related to its use. DESIGN: This
      study is a retrospective cohort study. SETTINGS: This study was conducted at a
      tertiary care medical center using Survey of Epidemiology and End Results
      Medicare data. PATIENTS: Patients with pathologic Tis, T1, or T2 rectal cancer
      who were >65 years of age and underwent primary radical resection or local
      excision between 2000 and 2009 were included in this study. MAIN OUTCOME
      MEASURES: The change in the use of local excision for rectal cancer from 2000 to
      2009 was the main outcome measured. RESULTS: A total of 8966 patients were
      identified. The use of local excision decreased significantly between 2000 and
      2009. Women and patients who were older and had more comorbidities were
      significantly more likely to undergo local excision. Having a colorectal surgeon
      perform the surgery increased the odds of local excision by 1.5 times (p <
      0.001). Similar trends were seen in patients operated on at the National Cancer
      Institute (OR, 1.7; p <0.001) and teaching hospitals (OR, 1.2; p = 0.003).
      Younger surgeons were more likely to perform local excisions. For surgeons
      graduating in 1980-1989 or 1990 and after, the odds of local excision were 1.40
      (p = 0.001) and 2.1 (p <0.001) compared with surgeons graduating before 1970.
      LIMITATIONS: The study was limited by the retrospective design, and the data were
      collected by multiple healthcare officials in their representative institutions.
      CONCLUSIONS: In patient >65 years of age, the odds of undergoing local excision
      for early stage rectal cancer decreased significantly between 2000 and 2009,
      coincident with evidence of oncologic inferiority. However, there was still
      significant variation in its use. More studies are needed to better understand
      these variations in an attempt to bring more uniformity to the use of local
      excision in early stage rectal cancer.

PMID- 25585075
TI  - Does extended surgery influence health-related quality of life in patients with
      rectal cancer?
AB  - BACKGROUND: In locally advanced rectal cancer, an extended resection peripheral
      to the mesorectal fascia is needed to achieve a radical resection. The influence
      of extended resections on health-related quality of life is unclear. OBJECTIVE:
      Differences in health-related quality of life and sexuality between patients
      receiving standard surgery and patients receiving extended surgery were examined,
      with a focus on age. DESIGN: Patients operated on for rectal cancer between 2000
      and 2010 were selected from a database and invited to complete the European
      Organization for Research and Treatment of Cancer quality-of-life questionnaires
      (C30 and ColoRectal 38). SETTINGS: All patients were treated at the Catharina
      Hospital, Eindhoven, the Netherlands. PATIENTS: All patients received total
      mesorectal excision surgery or extended surgery for rectal cancer. MAIN OUTCOME
      MEASURES: Health-related quality of life and sexual activity was compared between
      patients treated with total mesorectal excision surgery and extended surgery and
      further stratified by age at the time of surgery (<70 and >=70). RESULTS: Two
      hundred twenty-nine (64.1%) patients with standard surgery and 128 (35.9%)
      patients treated with extended resections responded. Extended surgery in patients
      <70 years resulted in lower body image compared with patients <70 years receiving
      standard surgery. Patients >=70 years had lower sexual function and more male
      sexual dysfunction than patients <70 years undergoing standard surgery. In all
      groups, sexual activity dropped significantly after treatment. LIMITATIONS: No
      information was available of the patients' health-related quality of life before
      treatment except for the retrospective question about sexual activity.
      CONCLUSIONS: This study showed no major differences between patients undergoing
      total mesorectal excision surgery and those receiving extended surgery, with the
      exception of body image, which was significantly lower in patients <70 years
      undergoing extended surgery. In all patient groups, treatment for rectal cancer
      influenced sexual activity dramatically. Awareness of the impact of surgery on
      health-related quality of life and sexuality is needed.

PMID- 25585076
TI  - Efficacy and safety of neoadjuvant intensity-modulated radiotherapy with
      concurrent capecitabine for locally advanced rectal cancer.
AB  - BACKGROUND: We previously conducted a prospective phase II clinical trial
      studying a unique 22-fraction neoadjuvant intensity-modulated radiotherapy with
      concurrent capecitabine treatment followed by total mesorectal excision for
      locally advanced rectal cancer. OBJECTIVE: The objective of this study was to
      retrospectively review the efficacy, toxicity, and surgical complications
      following intensity-modulated radiotherapy in patients who have rectal cancer.
      DESIGN: This was a retrospective study. SETTING: Data were gathered from a
      surgical database. PATIENTS: This study included patients who underwent intensity
      modulated radiotherapy with gross tumor volume/clinical target volume of
      50.6/41.8 Gy in 22 fractions with concurrent capecitabine treatment over a period
      of 30 days, after which the patients underwent surgery for rectal cancer in
      Peking University Cancer Hospital (2007-2013). MAIN OUTCOME MEASURES: The primary
      end points were acute toxicity, postoperative complications, and complete
      response rate. RESULTS: A total of 260 patients were included in our analysis.
      The median age was 55 years (range, 21-87 years), and 68.5% of the patients were
      male. The yield complete response rate was 18.5% (48/260). There were no grade 4
      toxicity and perioperative mortality. The grade 3 toxicity rate was 5.8%, which
      included diarrhea (4.2%), neutropenia (1.2%), and radiation dermatitis (0.4%).
      The 30-day postoperative and severe complication (>=grade 3) rates were 23.1% and
      2.7%. The anastomotic leakage rate was 3.3% (5/152). Perineal wound complications
      (29.2%, 28/96) represented the most common problem following abdominoperineal
      resection. The estimated 3-year local recurrence-free survival, cancer-specific
      survival, and disease-free survival rates were 94.2% (95% CI, 90.1%-98.3%), 92.2%
      (95% CI, 87.5%-97.0%), and 81.4% (95% CI, 75.4%-87.4%). LIMITATION: The
      retrospective nature and the single-arm design was the limitation of the study.
      CONCLUSION: The 22-fraction neoadjuvant intensity-modulated radiotherapy regimen
      used to treat rectal cancer in this study has a high efficacy rate and a low
      toxicity rate. Further studies are needed to better define the role of intensity
      modulated radiotherapy for rectal cancer treatment in a neoadjuvant setting.

PMID- 25585077
TI  - Does endoscopic ultrasound improve detection of locally recurrent anal squamous
      cell cancer?
AB  - BACKGROUND: Evaluating patients for recurrent anal cancer after primary treatment
      can be difficult owing to distorted anatomy and scarring. Many institutions
      incorporate endoscopic ultrasound to improve detection, but the effectiveness is
      unknown. OBJECTIVE: The aim of this study is to compare the effectiveness of
      digital rectal examination and endoscopic ultrasound in detecting locally
      recurrent disease during routine follow-up of patients with anal cancer. DESIGN:
      This study is a retrospective, single-institution review. SETTINGS: This study
      was conducted at an oncologic tertiary referral center. PATIENTS: Included were
      175 patients with nonmetastatic anal squamous-cell cancer, without persistent
      disease after primary chemoradiotherapy, who had at least 1 posttreatment
      ultrasound and examination by a colorectal surgeon. MAIN OUTCOME MEASURES: The
      primary outcomes measured were the first modality to detect local recurrence,
      concordance, crude cancer detection rate, sensitivity, specificity, and
      predictive value. RESULTS: Eight hundred fifty-five endoscopic ultrasounds and
      873 digital rectal examinations were performed during 35 months median follow-up.
      Overall, ultrasound detected 7 (0.8%) mesorectal and 32 (3.7%) anal canal
      abnormalities; digital examination detected 69 (7.9%) anal canal abnormalities.
      Locally recurrent disease was found on biopsy in 8 patients, all detected first
      or only with digital examination. Four patients did not have an ultrasound at the
      time of diagnosis of recurrence. The concordance of ultrasound and digital
      examination in detecting recurrent disease was fair at 0.37 (SE, 0.08; 95% CI,
      0.21-0.54), and there was no difference in crude cancer detection rate,
      sensitivity, specificity, and negative or positive predictive values.
      LIMITATIONS: The heterogeneity of follow-up timing and examinations is not
      standardized in this study but is reflective of general practice. CONCLUSIONS:
      Endoscopic ultrasound did not provide any advantage over digital rectal
      examination in identifying locally recurrent anal cancer, and should not be
      recommended for routine surveillance.

PMID- 25585078
TI  - National trends of 3- versus 2-stage restorative proctocolectomy for chronic
      ulcerative colitis.
AB  - BACKGROUND: Patients undergoing surgical treatment of chronic ulcerative colitis
      usually undergo a staged approach to IPAA. OBJECTIVE: The purpose of this work
      was to identify the national trends in approach to IPAA for chronic ulcerative
      colitis and to evaluate 30-day outcomes using the American College of Surgeons
      National Surgical Quality Improvement Program. DESIGN: This was a retrospective
      review study SETTINGS: : This study was conducted at a tertiary care cancer
      center. PATIENTS: Patients with chronic ulcerative colitis who underwent IPAA
      from 2005 to 2011 were identified. Those who underwent colectomy with pouch
      procedure were placed in a 2-stage cohort, and those without simultaneous
      colectomy were part of a 3-stage cohort. Emergent operations were excluded. MAIN
      OUTCOME MEASURES: Trends in procedure mix, preoperative characteristics, and
      postoperative 30-day outcomes were compared. Multivariate analysis was used to
      identify independent risk factors for postoperative infection. RESULTS: Of 2002
      patients who underwent IPAA, 1452 (72.5%) underwent 2-stage and 550 (27.5%)
      underwent 3-stage surgery. Since 2007, the distribution of 2- versus 3-stage
      procedures has not changed (p = 0.66). At the time of pouch surgery, patients who
      had undergone 3-stage surgery were less likely to have preoperative
      corticosteroid therapy, albumin <3 mg/dL, preoperative sepsis, and weight loss
      (all p < 0.05). Superficial surgical site infection was more common after 3-stage
      surgery (11.5% vs 7.3%; p < 0.01). After controlling for preoperative factors,
      wound classification was the only independent predictor of deep incisional or
      organ space infection (p < 0.01; OR, 1.76; 95% CI, 1.23-2.53). LIMITATIONS: This
      was a retrospective study. CONCLUSIONS: National trends of 2- versus 3-stage IPAA
      have remained stable over the last 5 years. Patients who underwent a 3-stage
      approach were healthier at the time of pouch surgery, with decreased
      corticosteroid use, hypoalbuminemia, and weight loss. Mixed results were seen for
      infectious complications with either approach. Prospective research is needed to
      determine the best approach to IPAA for chronic ulcerative colitis.

PMID- 25585079
TI  - Restorative proctocolectomy with a handsewn IPAA: S-pouch or J-pouch?
AB  - BACKGROUND: The efferent limb on the S-pouch fits well into the anal canal while
      the body of the pouch lies on the levators. In contrast, the blunt end of a J
      pouch may be distorted as it is forced into the muscular tube of the stripped
      anus. OBJECTIVE: The aim of this study is to compare the clinical outcomes and
      quality of life between patients with S- and J-pouches with a handsewn IPAA.
      DESIGN: This study was retrospective. SETTING: This study was conducted at a high
      volume tertiary referral center. PATIENTS: Patients undergoing a primary handsewn
      IPAA from 1983 to 2012 were identified. MAIN OUTCOMES MEASURES: Demographics,
      operative details, functional outcomes, and quality of life were abstracted.
      RESULTS: A total of 502 patients, including 169 patients with an S-pouch (33.7%)
      and 333 patients with J-pouch (66.3%), met our inclusion criteria; 55.8% (n =
      280) were men. Mean age at pouch construction was 37.8 +/- 12.5 years. Patients
      with an S-pouch were younger (p = 0.004) and had a higher BMI (p = 0.035) at
      pouch surgery. There was no significant difference between patients with S- or J
      pouches in other demographics. The frequencies of short-term complications in the
      2 groups were similar (p > 0.05), but pouch fistula or sinus (p = 0.047), pelvic
      sepsis (p = 0.044), postoperative partial small-bowel obstruction (p = 0.003), or
      postoperative pouch-related hospitalization (p = 0.021) occurred in fewer
      patients with an S-pouch. At a median follow-up of 12.2 (range, 4.3-20.1) years,
      patients with an S-pouch were found to have fewer bowel movements (p < 0.001),
      less frequent pad use (p = 0.001), and a lower fecal incontinence severity index
      score (p = 0.015). The pouch failed in 62 patients (12.4%), but neither
      univariate nor multivariate analysis showed a significant association with pouch
      configuration. LIMITATIONS: The use of data from a single tertiary referral
      center was a limitation of this study. CONCLUSION: We recommend using an S-pouch
      when constructing an IPAA with a handsewn technique.

PMID- 25585080
TI  - Anatomy of the inferior mesenteric artery evaluated using 3-dimensional CT
      angiography.
AB  - BACKGROUND: The branching of the inferior mesenteric artery and vein varies among
      individuals. Three-dimensional CT angiography is a less invasive modality than
      traditional angiographic examination to assess the artery and vein. OBJECTIVE: We
      aimed to demonstrate the clinical applicability of CT angiography by evaluating
      bifurcations of the inferior mesenteric artery and the positional relationship
      between the inferior mesenteric artery and vein. DESIGN: This was a prospective
      observational study of patients undergoing preoperative CT angiography. SETTINGS:
      This study was conducted at a single tertiary care institution in Japan.
      PATIENTS: A total of 471 consecutive patients who underwent preoperative CT
      angiography from April 2012 to December 2013 were prospectively enrolled. MAIN
      OUTCOME MEASURES: The branching pattern of the inferior mesenteric artery, the
      positional relationship between the inferior mesenteric artery and vein, and the
      associations between inferior mesenteric artery length and clinical features were
      evaluated. RESULTS: The length of the inferior mesenteric artery varied widely,
      from 10.1 to 82.2 mm. In 41.2% patients, the left colic artery arose
      independently from the sigmoid artery, and in 44.7% of the patients, the left
      colic artery and sigmoid artery had a common trunk, whereas the left colic artery
      did not exist in 5.1%. The left colic artery was located lateral to the inferior
      mesenteric vein at the level of the origin of the inferior mesenteric artery in
      73.0% of the patients. The incidence of a short inferior mesenteric artery was
      significantly increased in men with high BMIs (75.0%). LIMITATIONS: Three
      dimensional reconstruction was performed by the use of a single software, and
      angiographic examination was not performed. Therefore, accuracy and reliability
      of the 3-dimensional reconstruction could not be established for each modality.
      CONCLUSIONS: Using 3-dimensional CT angiography, preoperative understanding of
      the anatomic vascular variations can be easily obtained, which would help
      surgeons to safely perform laparoscopic surgery in the left-side colon and
      rectum.

PMID- 25585081
TI  - Visceral obesity, not elevated BMI, is strongly associated with incisional hernia
      after colorectal surgery.
AB  - BACKGROUND: High BMI is often used as a proxy for obesity and has been considered
      a risk factor for the development of an incisional hernia after abdominal
      surgery. However, BMI does not accurately reflect fat distribution. OBJECTIVE:
      The purpose of this work was to investigate the relationship among different
      obesity measurements and the risk of incisional hernia. DESIGN: This was a
      retrospective cohort study. SETTINGS: The study included a single academic
      institution in New York from 2003 to 2010. PATIENTS: The study consists of 193
      patients who underwent colorectal cancer resection. MAIN OUTCOME MEASURES:
      Preoperative CT scans were used to measure visceral fat volume, subcutaneous fat
      volume, total fat volume, and waist circumference. A diagnosis of incisional
      hernia was made either through physical examination in medical chart
      documentation or CT scan. RESULTS: Forty-one patients (21.2%) developed an
      incisional hernia. The median time to hernia was 12.4 months. After adjusting for
      patient and surgical characteristics using Cox regression analysis, visceral
      obesity (HR 2.04, 95% CI 1.07-3.91) and history of an inguinal hernia (HR 2.40,
      95% CI 1.09-5.25) were significant risk factors for incisional hernia.
      Laparoscopic resection using a transverse extraction site led to a >75% reduction
      in the risk of incisional hernia (HR 0.23, 95% CI 0.07-0.76). BMI > 30 kg/m was
      not significantly associated with incisional hernia development. LIMITATIONS:
      Limitations include the retrospective design without standardized follow-up to
      detect hernias and the small sample size attributed to inadequate or unavailable
      CT scans. CONCLUSIONS: Visceral obesity, history of inguinal hernia, and location
      of specimen extraction site are significantly associated with the development of
      an incisional hernia, whereas BMI is poorly associated with hernia development.
      These findings suggest that a lateral transverse location is the incision site of
      choice and that new strategies, such as prophylactic mesh placement, should be
      considered in viscerally obese patients.

PMID- 25585082
TI  - Partial lateral internal sphincterotomy versus combined botulinum toxin A
      injection and topical diltiazem in the treatment of chronic anal fissure: a
      randomized clinical trial.
AB  - OBJECTIVES: The aim of this study is to evaluate the effectiveness and
      complications associated with combined topical diltiazem cream and botulinum
      toxin A injection versus partial lateral internal sphincterotomy in chronic anal
      fissure. DESIGN: This study is a parallel, randomized controlled trial (using the
      block randomization method). SETTING: This study was performed at a university
      hospital in Iran. PARTICIPANTS: Ninety-nine patients who had chronic anal
      fissures were included. INTERVENTION: A total of 99 patients were randomly
      assigned to 2 groups; the first group received combined topical diltiazem
      ointment (for 6 weeks) and botulinum toxin A injection (once) (n = 49), and the
      second group received partial lateral internal sphincterotomy (n = 50). All the
      patients were followed up for 1 year. MAIN OUTCOME MEASURES: The primary outcomes
      measured were the healing of the anal fissure and the development of incontinence
      as the major adverse event during the 1-year follow-up period. RESULTS: The
      overall healing rate was 65% and 94% in the botulinum toxin A-diltiazem and
      partial lateral internal sphincterotomy groups (p < 0.001). The patients in the
      partial lateral internal sphincterotomy group experienced significantly higher
      incontinence scores (p = 0.04) according to the Cleveland Clinic Florida-Fecal
      Incontinence scoring system. In patients who had chronic anal fissure for <=12
      months, no statistical difference was observed in the healing rate between the
      botulinum toxin A-diltiazem and partial lateral internal sphincterotomy groups
      (100% vs 100%). However, in the patients with longer chronic fissures, the
      healing rate was significantly higher in the partial lateral internal
      sphincterotomy group (86% [18/21] vs 23% [5/21], p < 0.001). LIMITATIONS: The 1
      year follow-up period, subjective definitions of itching, and lack of anorectal
      manometry examinations and data regarding the effect of each treatment on anal
      sphincter pressure at rest and contraction are the key limitations of this study.
      CONCLUSION: Combined botulinum toxin A injection with a topical application of
      diltiazem could be as effective as partial lateral internal sphincterotomy in the
      treatment of chronic anal fissure in patients who have chronic anal fissure for
      <=12 months. However, in chronic anal fissures of longer duration, partial
      lateral internal sphincterotomy is associated with a significantly higher cure
      rate.

PMID- 25585083
TI  - Sacral nerve modulation for fecal incontinence: results of a prospective single
      center randomized crossover study.
AB  - BACKGROUND: Although sacral nerve modulation has become an important tool for the
      treatment of fecal incontinence, prospective, randomized data are still rare.
      OBJECTIVE: To determine the effectiveness of sacral nerve modulation in a
      prospective randomized crossover study DESIGN: : Prospective randomized crossover
      study SETTING: : Proctological Office and Department of Surgical Proctology at a
      private hospital. PATIENTS: A total of 31 consecutive patients (31 women) aged 55
      +/- 12 years (median +/- SD) with fecal incontinence were enrolled between
      February 2012 and December 2012. INTERVENTIONS: All patients underwent sacral
      nerve modulation through a staged implantation procedure between 2009-2011. After
      a median of 26.8 months following implantation, 16 of the 31 patients agreed to
      be randomized in a crossover design to stimulation ON or OFF, each for a 3-week
      period. After the two periods (ie, 6 weeks), while still blinded to the
      stimulator status, the patients chose which stimulation period (first or second)
      they preferred. The mode of stimulation corresponding to the selected period was
      then continued for 3 months (final period). MAIN OUTCOME MEASURES: Frequency of
      bowel movements, frequency of fecal incontinence and urgency episodes, severity
      scores, preference for ON or OFF. RESULTS: The frequency of fecal incontinence
      episodes and Cleveland Clinic Incontinence Score (CCIS) were both significantly
      lower in the ON period than the OFF period (p < 0.005) during the crossover phase
      of the study. All patients decided to stay in the ON mode for the final period
      and have continued in the ON mode until now. LIMITATIONS: Small patient numbers.
      CONCLUSIONS: The significant improvement in fecal incontinence during the ON
      period, as compared to the OFF period, makes it unlikely that the observed
      benefits of sacral nerve modulation are due to a placebo effect.

PMID- 25585084
TI  - Initial results of a new bulking agent for fecal incontinence: a multicenter
      study.
AB  - BACKGROUND: Anal incontinence is a common and multifactorial pathology that
      affects patients' lives and imposes considerable socioeconomic consequences.
      OBJECTIVE: The aim of this study is to evaluate the efficacy of a bulking agent,
      polyacrylate-polyalcohol (PP), in terms of diminishing the severity of
      incontinence and improving the patient's quality of life, assessing any adverse
      events. DESIGN: Data were obtained through a prospective, nonconsecutive,
      multicenter, noncomparative, postmarket study with a maximum expected follow-up
      of 3 years. Four investigational centers from Argentina and Brazil participated
      in this study. SETTINGS: Injections of the bulking agent were administered in the
      operating room of tertiary hospitals. PATIENTS: Fifty-eight patients were
      enrolled. Five patients were lost to follow-up. Of the remaining 53 patients, 41
      (77.4%) were females. All patients scored between 6 and 12 on the Cleveland
      Clinic Florida-Fecal Incontinence Score as part of the inclusion criteria.
      INTERVENTIONS: The injection of the bulking agent (PP) was administered under
      intravenous sedation in the submucosa of the anal canal through the perianal skin
      to generate a bulk. MAIN OUTCOME MEASURES: The primary efficacy end point was the
      Cleveland Clinic Florida-Fecal Incontinence Score (or Jorge and Wexner index).
      The Rockwood-Fecal Incontinence Quality of Life index was also recorded. The
      treatment was considered successful if patients achieved a postoperative
      improvement of at least 50% on the Cleveland Clinic Florida-Fecal Incontinence
      Score. RESULTS: Successful treatment was met by 60.4% of the patients according
      to the last follow-up data. Quality-of-life indices showed consistently
      significant improvements. LIMITATIONS: Selection bias and the lack of a control
      group to evaluate the potential placebo effect of this novel bulking agent were
      limitations of this study. Because of the eligibility criteria, the resulting
      patient sample is representative of only a limited portion of the population with
      fecal incontinence at all 4 centers involved in this study. CONCLUSIONS: The
      injection technique was easy to perform, safe, and ideal for use as an outpatient
      procedure. This bulking agent (PP) significantly improved continence and quality
      of life in selected patients.

PMID- 25585085
TI  - Can the national surgical quality improvement program provide surgeon-specific
      outcomes?
AB  - BACKGROUND: Efforts to improve the quality of surgical care and reduce morbidity
      and mortality have resulted in outcomes reporting at the service and
      institutional level. Surgeon-specific outcomes are not readily available.
      OBJECTIVE: The aim of this study is to compare surgeon-specific outcomes from the
      National Surgical Quality Improvement Program and 100% capture institutional
      quality data. DESIGN: We conducted a cohort study evaluating institutional and
      surgeon-specific outcomes following colorectal surgery procedures at 1
      institution over 5 years. PATIENTS: All patients who underwent an operation by a
      colorectal surgeon at Lahey Hospital & Medical Center from January 1, 2008
      through December 31, 2012 were identified. MAIN OUTCOME MEASURES: Thirty-day
      mortality, reoperation, urinary tract infection, deep vein thrombosis, pneumonia,
      superficial surgical site infection, and organ space infection were the primary
      outcomes measured. ANALYSIS: We compared annual and 5-year institutional and
      surgeon-specific adverse event rates between the data sets. In addition, we
      categorized individual surgeons as low-outlier, average, or high-outlier in
      relation to aggregate averages and determined the concordance between the data
      sets in identifying outliers. Concordance was designated if the 2 databases
      classified outlier status similarly for the same adverse event category. RESULTS:
      In the 100% capture institutional data, 6459 operative encounters were identified
      in comparison with 1786 National Surgical Quality Improvement Program encounters
      (28% sampled). Annual aggregate adverse event rates were similar between the
      institutional data and the National Surgical Quality Improvement Program. For
      annual surgeon-specific comparisons, concordance in identifying outliers between
      the 2 data sets was 51.4%, and gross discordance between outlier status was in
      8.2%. Five-year surgeon-specific comparisons demonstrated 59% concordance in
      identifying outlier status with 8.2% gross discordance for the group.
      LIMITATIONS: The inclusion of data from only 1 academic referral center is a
      limitation of this study. CONCLUSIONS: Each surgeon was identified as a "high
      outlier" in at least 1 adverse event category. Comparisons at the annual and 5
      year points demonstrated poor concordance between our 100% capture institutional
      data and the National Surgical Quality Improvement Program data.

PMID- 25585086
TI  - Transanal endoscopic microsurgery versus standard transanal excision for the
      removal of rectal neoplasms: a systematic review and meta-analysis.
AB  - BACKGROUND: Transanal endoscopic microsurgery is the intraluminal excision of
      rectal lesions with the use of instrumentation to maintain a stable pneumorectum,
      enabling a magnified view of the target lesion. Despite suggested benefits over
      traditional transanal excision, there is no consensus on which technique is
      superior. OBJECTIVE: The aim of the current study is to use meta-analytical
      techniques to compare transanal endoscopic microsurgery with transanal excision.
      DATA SOURCES: A comprehensive literature search of PubMed, Embase, and The
      Cochrane Library was performed. STUDY SELECTION: All studies comparing transanal
      endoscopic microsurgery with transanal excision were included. INTERVENTIONS:
      Transanal endoscopic microsurgery was compared with transanal excision by using
      random-effects methods to combine data. Data are presented as ORs with 95% CIs.
      MAIN OUTCOME MEASURES: The main outcomes measured were postoperative complication
      rate, negative microscopic margin rate, specimen fragmentation rate, and lesion
      recurrence. RESULTS: Six comparative series comparing outcomes following 927
      local excisions were identified. There was no difference between techniques in
      postoperative complication rate (OR, 1.018; 95% CI, 0.658-1.575; p = 0.937).
      Transanal endoscopic microsurgery had a higher rate of negative microscopic
      margins in comparison with transanal excision (OR, 5.281; 95% CI, 3.201-8.712; p
      < 0.001). Transanal endoscopic microsurgery had a reduced rate of specimen
      fragmentation (OR, 0.096; 95% CI, 0.044-0.209; p < 0.001) and lesion recurrence
      (OR, 0.248; 95% CI, 0.154-0.401; p < 0.001) compared with transanal excision.
      There was no across-study heterogeneity for any end point. LIMITATIONS: Most
      studies were retrospectively designed, and there were variations in patient
      populations and duration of follow-up. CONCLUSIONS: Available data are limited
      because of a lack of randomized controlled trials. However, based on current
      evidence, transanal endoscopic microsurgery is oncologically superior to
      transanal excision for the excision of rectal neoplasms.

PMID- 25585087
TI  - Preoperative angioembolization of Bushke-Lowenstein tumor: an innovative,
      alternative approach to reduce perioperative blood loss for exceptionally large
      tumors.

PMID- 25585088
TI  - The need for standardization of colonoscopic tattooing of colonic lesions.

PMID- 25585089
TI  - The need for standardization of colonoscopic tattooing of colonic lesions.

PMID- 25585090
TI  - Colonic salvage with antiperistaltic cecorectal anastomosis.
AB  - BACKGROUND: Following colon resection, the construction of a well-perfused,
      tension-free isoperistaltic anastomosis can be made difficult by multiple factors
      including prior abdominal surgery or compromised vascular supply. Here, we
      describe the technique of antiperistaltic cecorectal anastomosis as a method for
      preserving viable colon without compromising functional outcome. TECHNIQUE:
      Following extensive colorectal resection, different techniques for isoperistaltic
      reconstruction using the cecum and ascending colon have been described, including
      the Deloyers procedure and limited isoperistaltic cecorectal anastomosis.
      However, these isoperistaltic reconstructions often require ligation of the
      middle colic and right colic arteries and/or sacrifice of viable distal colon to
      aid reconstruction. In complex situations that require preservation of normal
      vascular anatomy, an antiperistaltic cecorectal anastomosis can be constructed
      that maintains the orientation of the vascular pedicle. In addition to the
      preservation of the colonic arterial supply, a distinguishing feature of this
      technique is the substantial portion of antiperistaltic colon that is preserved
      and interposed to reestablish continuity. RESULTS: In a case where it was used,
      construction of an antiperistaltic cecorectal anastomosis was technically
      successful and led to a good functional outcome. CONCLUSION: Antiperistaltic
      cecorectal anastomosis should be considered as an option in colonic
      reconstruction for patients with extensive prior abdominal surgery or when
      complex anatomic issues require preservation of native vascular anatomy. In these
      situations, this technique offers several advantages over isoperistaltic
      reconstruction and may be the only option for reconstruction that uses the
      remaining cecum and colon.

PMID- 25585091
TI  - Cost-effectiveness of laparoscopy in rectal cancer: should China take a second
      look?

PMID- 25585092
TI  - Perineal wound healing after abdominoperineal resection for rectal cancer: a
      systematic review and meta-analysis.

PMID- 25585093
TI  - The authors reply.

PMID- 25585096
TI  - Preterm labor: role of the nurse practitioner.
AB  - The nurse practitioner may play a pivotal role in diagnosing preterm labor
      through risk assessment and physical exam. While treatment and management of
      preterm labor are usually beyond the nurse practitioner's scope of practice, they
      can play an important role in preventing preterm birth through assessment,
      action, or advocacy. 

PMID- 25585097
TI  - In-vitro study on ureteral smooth muscle contractility with tamsulosin,
      nifedipine, and terpene mixture (Rowatinex(r)).
AB  - AIM: The aim of this study was to evaluate whether tamsulosin, an alpha-blocker,
      has an effect on decreasing spontaneous ureteral contractility with or without
      phenylephrine, an alpha-agonist. Additionally, nifedipine and a terpene mixture
      (Rowatinex(r)) were tested and compared with each other. METHODS: We obtained
      ureteral segments from freshly killed eight-week-old rabbits. Preparation was
      performed in an aerated Krebs buffer (95% oxygen and 5% carbon dioxide) at a
      constant temperature of 37  degrees C. All segments were suspended into organ
      tissue baths containing aerated Krebs buffer using stainless steel hangers and
      clips. The ureter was divided into four segments: upper, middle, low and uretero
      vesical junction. Each ureteral segment was suspended longitudinally and
      circularly by opposite corners, respectively. Tamsulosin, nifedipine, and the
      terpene mixture were separately applied into the segments. Contractile activities
      of each drug were recorded and analyzed by the PowerLab data acquisition system
      (AD instruments CO., USA). The area under the curve was compared between before
      and after each drug application for each 5 minutes with or without pheylephrine.
      Statistical analysis was performed using the unpaired Student's t test. RESULTS:
      Under Krebs solution, ureteral smooth muscle contractility was significantly
      decreased in all segments over 10(-6) M in tamsulosin, 10(-7) M in nifedipine and
      0.001x1 concentrations in the terpene mixture (P=0.038). However, under Krebs
      solution with 10(-5) M phenylephrine, there was no significant difference at all
      concentrations in tamsoluin and nifedipine. In contrast to tamsolusin and
      nifedipine, there was a significant decrease in ureteral smooth muscle
      contractility in most of segments at 0.01x1 concentrations (P=0.042) in the
      terpene mixture. CONCLUSION: Tamsulosin, nifedipine, and the terpene mixture
      showed the effect on spontaneous ureteral contractility. In particular, the
      terpene mixture might have the better effect on decreasing ureteral smooth muscle
      contractility.

PMID- 25585098
TI  - Long-term outcomes of transobturator tape procedure in women with stress and
      mixed urinary incontinence: 5-year follow-up.
AB  - BACKGROUND: The aim of this study was to compare the postoperative outcomes and
      complications of transobturator tape (TOT) procedure in women with mixed urinary
      incontinence (MUI) and stress urinary incontinence (SUI) in long term follow-up.
      METHODS: A group of 193 women, who underwent TOT procedure, was documented in the
      study. Patients were divided into two groups in terms of incontinence type. Group
      1 consists of patients with SUI and group 2 with MUI. All patients were evaluated
      with pelvic examination, including cough stress test and international
      consultation on incontinence questionnaire-short form at 3 and 12 months and
      annually. Visual Analog Scale (VA S) was used to evaluate postoperative patient
      satisfaction. Two groups were retrospectively compared for postoperative
      complication, patient satisfaction, objective and subjective cure rates. RESULTS:
      In this study, group 1 included 105 patients and 67 patients were in group 2.
      There was no significant difference between the objective cure rates in two
      groups; however subjective cure and patients satisfaction rates were
      significantly higher in SUI group (P<0.05). Complications were reported according
      to the Clavien-Dindo classification with Gr I 8.3%, Gr II 66.7%, Gr IIIa 8.3% and
      Gr IIIb 16.7% and Gr I 16.7%, Gr II 66.6%, Gr IIIa 16.7% and Gr IIIb 0% in group
      1 and group 2, respectively. CONCLUSIONS: It is not easy to identify an ideal
      treatment modality for women with MUI but TOT procedure seems to be effective and
      safe in the surgical treatment of MUI after 5 years follow-up.

PMID- 25585099
TI  - Simultaneous delivery of BMP-2 factor and anti-osteoporotic drugs using
      hyaluronan-assembled nanocomposite for synergistic regulation on the behaviors of
      osteoblasts and osteoclasts in vitro.
AB  - To treat the osteoporosis and regulate the biological behaviors of both
      osteoblasts and osteoclasts, we prepared a natural polysaccharide-derived
      nanocomposite, containing alendronate-grafted hyaluronate (HA-Aln) and bone
      morphogenetic protein 2 (BMP-2) and investigated its synergistic regulation on
      the behaviors of osteoblasts and osteoclasts in vitro. The HA-Aln/BMP-2
      nanocomposite was fabricated through the electrostatic interactions between the
      HA-Aln molecule and BMP-2 molecule. Here, BMP-2 was used to improve the
      osteoblast-mediated bone formation. Alendronate (Aln), a targeting ligand to bone
      matrix, was used to inhibit the osteoclast-mediated bone resorption. In vitro
      results showed that HA-Aln/BMP-2 nanocomposite could effectively maintain the
      bioactivity of loaded drugs. The osteoblasts that treated with the HA-Aln/BMP-2
      nanocomposite presented a higher level of cell motility, alkaline phosphatase
      (ALP) activity, mineralization capacity, and osteoblast-related gene expressions
      (runt-related transcription factor 2, osterix, ALP, collagen type I, osteocalcin,
      and osteopontin), as compared to that of control group. Besides, the RAW264.7
      cells that were treated with HA-Aln/BMP-2 nanocomposite showed a lower level of
      osteoclastic differentiation. Overall, the HA-Aln/BMP-2 nanocomposite exhibits
      promising potential as an efficient carrier for co-delivery of anti-osteoporotic
      drug and growth factors to promote osteoblastic differentiation and bone
      formation while suppressing osteoclastic activity. 

PMID- 25585101
TI  - Functionalized multi-walled carbon nanotubes in an aldol reaction.
AB  - The covalent functionalization of multi-walled carbon nanotubes (MWCNTs) with a
      proline-based derivative is reported. Initially, MWCNTs were oxidized in order to
      introduce a large number of carboxylic units on their tips followed by N-tert
      butoxycarbonyl-2,2'(ethylenedioxy)bis-(ethylamine) conjugation through an amide
      bond. Then, a proline derivative bearing a carboxylic terminal moiety at the 4
      position was coupled furnishing proline-modified MWCNTs. This new hybrid material
      was fully characterized by spectroscopic and microscopy means and its catalytic
      activity in the asymmetric aldol reaction between acetone and 4-nitrobenzaldehyde
      was evaluated for the first time, showing to proceed almost quantitatively in
      aqueous media. Furthermore, several amino-modified MWCNTs were prepared and
      examined in the particular aldol reaction. These new hybrid materials exhibited
      an enhanced catalytic activity in water, contrasting with the pristine MWCNTs as
      well as the parent organic molecule, which failed to catalyze the reaction
      efficiently. Furthermore, the modified MWCNTs proved to catalyze the aldol
      reaction even after three repetitive cycles. Overall, a green approach for the
      aldol reaction is presented, where water can be employed as the solvent and
      modified MWCNTs can be used as catalysts, which can be successfully recovered and
      reused, while their catalytic activity is retained. 

PMID- 25585102
TI  - Palladium on plastic substrates for plasmonic devices.
AB  - Innovative chips based on palladium thin films deposited on plastic substrates
      have been tested in the Kretschmann surface plasmon resonance (SPR)
      configuration. The new chips combine the advantages of a plastic support that is
      interesting and commercially appealing and the physical properties of palladium,
      showing inverted surface plasmon resonance (ISPR). The detection of DNA chains
      has been selected as the target of the experiment, since it can be applied to
      several medical early diagnostic tools, such as different biomarkers of cancers
      or cystic fibrosis. The results are encouraging for the use of palladium in SPR
      based sensors of interest for both the advancement of biodevices and the
      development of hydrogen sensors. 

PMID- 25585100
TI  - Pancreatic cancer, treatment options, and GI-4000.
AB  - Although pancreatic cancer is but the eleventh most prevalent cancer in the US,
      it is predicted that of all the patients newly diagnosed with this disease in
      2014, only 27% will still be alive at the end of the first year and only 6% will
      make it past 5 years. The choice of chemotherapy in the treatment of pancreatic
      cancer is dependent on disease stage and patient performance status but, in
      general, the most widely used approved regimens include 5-fluorouracil (5-FU)
      combinations and gemcitabine combinations. Recent therapeutic strategies have
      resulted in an improvement in survival of patients with pancreatic cancer but the
      magnitude of change is disappointing and vast improvements are still needed. The
      goal of immunotherapy is to enhance and guide the body's immune system to
      recognize tumor-specific antigens and mount an attack against the disease. Among
      newer immune therapies, GI-4000 consists of 4 different targeted molecular
      immunogens, each containing a different Ras protein (antigen) encoded by the most
      commonly found mutant RAS genes in solid tumors--RAS mutations exist in over 90%
      of pancreatic ductal adenocarcinomas. We will review pancreatic cancer
      epidemiology and its current treatment options, and consider the prospects of
      immunotherapy, focusing on GI-4000. We discuss the potential mechanism of action
      of GI-4000, and the performance of this vaccination series thus far in early
      phase clinical trials.

PMID- 25585103
TI  - Application of PTR-MS for measuring odorant emissions from soil application of
      manure slurry.
AB  - Odorous volatile organic compounds (VOC) and hydrogen sulfide (H2S) are emitted
      together with ammonia (NH3) from manure slurry applied as a fertilizer, but
      little is known about the composition and temporal variation of the emissions. In
      this work, a laboratory method based on dynamic flux chambers packed with soil
      has been used to measure emissions from untreated pig slurry and slurry treated
      by solid-liquid separation and ozonation. Proton-transfer-reaction mass
      spectrometry (PTR-MS) was used to provide time resolved data for a range of VOC,
      NH3 and H2S. VOC included organic sulfur compounds, carboxylic acids, phenols,
      indoles, alcohols, ketones and aldehydes. H2S emission was remarkably observed to
      take place only in the initial minutes after slurry application, which is
      explained by its high partitioning into the air phase. Long-term odor effects are
      therefore assessed to be mainly due to other volatile compounds with low odor
      threshold values, such as 4-methylphenol. PTR-MS signal assignment was verified
      by comparison to a photo-acoustic analyzer (NH3) and to thermal desorption GC/MS
      (VOC). Due to initial rapid changes in odorant emissions and low concentrations
      of odorants, PTR-MS is assessed to be a very useful method for assessing odor
      following field application of slurry. The effects of treatments on odorant
      emissions are discussed. 

PMID- 25585104
TI  - A fiber-tip label-free biological sensing platform: a practical approach toward
      in-vivo sensing.
AB  - The platform presented here was devised to address the unmet need for real time
      label-free in vivo sensing by bringing together a refractive index transduction
      mechanism based on Whispering Gallery Modes (WGM) in dye doped microspheres and
      Microstructured Optical Fibers. In addition to providing remote excitation and
      collection of the WGM signal, the fiber provides significant practical advantages
      such as an easy manipulation of the microresonator and the use of this sensor in
      a dip sensing architecture, alleviating the need for a complex microfluidic
      interface. Here, we present the first demonstration of the use of this approach
      for biological sensing and evaluate its limitation in a sensing configuration
      deprived of liquid flow which is most likely to occur in an in vivo setting. We
      also demonstrate the ability of this sensing platform to be operated above its
      lasing threshold, enabling enhanced device performance. 

PMID- 25585105
TI  - Fault diagnosis of rolling bearing based on fast nonlocal means and envelop
      spectrum.
AB  - The nonlocal means (NL-Means) method that has been widely used in the field of
      image processing in recent years effectively overcomes the limitations of the
      neighborhood filter and eliminates the artifact and edge problems caused by the
      traditional image denoising methods. Although NL-Means is very popular in the
      field of 2D image signal processing, it has not received enough attention in the
      field of 1D signal processing. This paper proposes a novel approach that
      diagnoses the fault of a rolling bearing based on fast NL-Means and the envelop
      spectrum. The parameters of the rolling bearing signals are optimized in the
      proposed method, which is the key contribution of this paper. This approach is
      applied to the fault diagnosis of rolling bearing, and the results have shown the
      efficiency at detecting roller bearing failures. 

PMID- 25585106
TI  - Average dielectric property analysis of complex breast tissue with microwave
      transmission measurements.
AB  - Prior information about the average dielectric properties of breast tissue can be
      implemented in microwave breast imaging techniques to improve the results.
      Rapidly providing this information relies on acquiring a limited number of
      measurements and processing these measurement with efficient algorithms.
      Previously, systems were developed to measure the transmission of microwave
      signals through breast tissue, and simplifications were applied to estimate the
      average properties. These methods provided reasonable estimates, but they were
      sensitive to multipath. In this paper, a new technique to analyze the average
      properties of breast tissues while addressing multipath is presented. Three steps
      are used to process transmission measurements. First, the effects of multipath
      were removed. In cases where multipath is present, multiple peaks were observed
      in the time domain. A Tukey window was used to time-gate a single peak and,
      therefore, select a single path through the breast. Second, the antenna response
      was deconvolved from the transmission coefficient to isolate the response from
      the tissue in the breast interior. The antenna response was determined through
      simulations. Finally, the complex permittivity was estimated using an iterative
      approach. This technique was validated using simulated and physical homogeneous
      breast models and tested with results taken from a recent patient study. 

PMID- 25585107
TI  - A proxy design to leverage the interconnection of CoAP Wireless Sensor Networks
      with Web applications.
AB  - In this paper, we present the design of a Constrained Application Protocol (CoAP)
      proxy able to interconnect Web applications based on Hypertext Transfer Protocol
      (HTTP) and WebSocket with CoAP based Wireless Sensor Networks. Sensor networks
      are commonly used to monitor and control physical objects or environments. Smart
      Cities represent applications of such a nature. Wireless Sensor Networks gather
      data from their surroundings and send them to a remote application. This data
      flow may be short or long lived. The traditional HTTP long-polling used by Web
      applications may not be adequate in long-term communications. To overcome this
      problem, we include the WebSocket protocol in the design of the CoAP proxy. We
      evaluate the performance of the CoAP proxy in terms of latency and memory
      consumption. The tests consider long and short-lived communications. In both
      cases, we evaluate the performance obtained by the CoAP proxy according to the
      use of WebSocket and HTTP long-polling. 

PMID- 25585108
TI  - The development and validation of the childhood obesity prevention self-efficacy
      (COP-SE) survey.
AB  - BACKGROUND: Physicians can play an important role in preventing and treating
      childhood obesity. There are currently no validated measures of medical students'
      self-efficacy in these skills; therefore, we sought to develop a valid and
      reliable computerized survey to measure medical students' self-efficacy in skills
      needed to prevent and treat childhood obesity. METHODS: We developed the
      Childhood Obesity Prevention Self-Efficacy (COP-SE) survey with input from two
      expert panels and cognitive interviews with medical students. We administered the
      43-item COP-SE computerized survey to a nation-wide sample of medical students.
      RESULTS: The final sample consisted of 444 medical students from 53 medical
      schools. Exploratory factor analysis revealed a two-factor structure with a
      correlation of 0.637 between factors and high reliability within factors. The
      correlation between the COP-SE and a measure of general self-efficacy was
      moderate (0.648), and reliability within factors was high (Factor 1=0.946; Factor
      2=0.927). CONCLUSIONS: The 18-item COP-SE is a valid and reliable measure of
      childhood obesity prevention self-efficacy. Factor 1 assesses self-efficacy in
      nutrition counseling, and Factor 2 measures self-efficacy to assess readiness to
      change and initiate nutrition lifestyle changes. The correlation between the COP
      SE and a measure of general self-efficacy indicates that the COP-SE is a
      distinct, valid assessment of domain-specific self-efficacy. The high reliability
      of items within factors indicates the items measure the same constructs.
      Therefore, medical schools can use this valid and reliable instrument as a
      formative or summative assessment of students' self-efficacy in childhood obesity
      prevention and treatment.

PMID- 25585122
TI  - Kinetics and product branching fractions of reactions between a cation and a
      radical: Ar(+) + CH3 and O2(+) + CH3.
AB  - A novel technique is described for the measurement of rate constants and product
      branching fractions of thermal reactions between cation and radical species. The
      technique is a variant of the variable electron and neutral density attachment
      mass spectrometry (VENDAMS) method, employing a flowing afterglow-Langmuir probe
      apparatus. A radical species is produced in situ via dissociative electron
      attachment to a neutral precursor; this allows for a quantitative derivation of
      the radical concentration and, as a result, a quantitative determination of rate
      constants. The technique is applied to the reactions of Ar(+) and O2(+) with CH3
      at 300 K. The Ar(+) + CH3 reaction proceeds near the collisional rate constant of
      1.1 * 10(-9) cm(3) s(-1) and has three product channels: -> CH3(+) + Ar (k = 5 +/
      2 * 10(-10) cm(3) s(-1)), -> CH2(+) + H + Ar (k = 7 +/- 2 * 10(-10) cm(3) s(
      1)), -> CH(+) + H2 + Ar (k = 5 +/- 3 * 10(-11) cm(3) s(-1)). The O2(+) + CH3
      reaction is also efficient, with direct charge transfer yielding CH3(+) as the
      primary product channel. Several results needed to support these measurements are
      reported, including the kinetics of Ar(+) and O2(+) with CH3I, electron
      attachment to CH3I, and mutual neutralization of CH3(+) and CH2(+) with I(-). 

PMID- 25585121
TI  - Clozapine and GABA transmission in schizophrenia disease models: establishing
      principles to guide treatments.
AB  - Schizophrenia disease models are necessary to elucidate underlying changes and to
      establish new therapeutic strategies towards a stage where drug efficacy in
      schizophrenia (against all classes of symptoms) can be predicted. Here we
      summarise the evidence for a GABA dysfunction in schizophrenia and review the
      functional neuroanatomy of five pathways implicated in schizophrenia, namely the
      mesocortical, mesolimbic, ventral striopallidal, dorsal striopallidal and
      perforant pathways including the role of local GABA transmission and we describe
      the effect of clozapine on local neurotransmitter release. This review also
      evaluates psychotropic drug-induced, neurodevelopmental and environmental disease
      models including their compatibility with brain microdialysis. The validity of
      disease models including face, construct, etiological and predictive validity and
      how these models constitute theories about this illness is also addressed. A
      disease model based on the effect of the abrupt withdrawal of clozapine on GABA
      release is also described. The review concludes that while no single animal model
      is entirely successful in reproducing schizophreniform symptomatology, a disease
      model based on an ability to prevent and/or reverse the abrupt clozapine
      discontinuation-induced changes in GABA release in brain regions implicated in
      schizophrenia may be useful for hypothesis testing and for in vivo screening of
      novel ligands not limited to a single pharmacological class.

PMID- 25585124
TI  - Platelet activity in the pathophysiology of inflammatory bowel diseases.
AB  - Platelets play a crucial role in immune responses. Impaired platelet activation
      may cause persistent mucosal inflammation through P-selectin, CD40-CD40L and
      other systems influencing granulocytes, macrophages or endothelial cells.
      Pharmacological regulation of platelet activation may reduce thromboembolism and
      limit the interaction of platelets with endothelial and inflammatory cells, in
      turn weakening the inflammatory responses. In this review we focus on
      pathophysiological activities of platelets in inflammatory bowel diseases and
      discuss the studies on currently available anti-platelet therapies in the
      treatment of gastrointestinal inflammation. Finally, we provide a prospective
      view to new anti-platelet agents currently under development. 

PMID- 25585123
TI  - Physical activity patterns of people affected by depressive and anxiety disorders
      as measured by accelerometers: a cross-sectional study.
AB  - BACKGROUND: Exercise can relieve both depressive and anxiety disorders and it is
      therefore of importance to establish movement patterns of mildly to moderately
      affected sufferers to estimate the treatment potential. The aim is to describe
      the physical activity patterns of people affected by mild to moderate depressive
      and/or anxiety symptoms using objective measures of physical activity. METHODS:
      The design of the study was cross-sectional using data from 165 people aged 18-65
      years, with mild to moderate depressive and/or anxiety disorder symptoms (scoring
      >= 10 on the PHQ-9). Diagnoses were made using Mini International
      Neuropsychiatric Interview (MINI) and symptom severity was measured with the
      Montgomery-Asberg Depression Rating Scale (MADRS). The participants wore
      accelerometers for a week to evaluate physical activity patterns. RESULTS: No
      statistically significant differences were detected between different diagnoses,
      though depressed participants tended to be less active and more sedentary. Only
      one-fifth of the sample followed public health guidelines regarding physical
      activity. Each one point increase in MADRS was associated with a 2.4 minute
      reduction in light physical activity, independent of moderate-to-vigorous
      physical activity and sedentary time. MADRS was positively associated with number
      of sedentary bouts. CONCLUSIONS: The physical activity pattern of people with
      depressive and/or anxiety disorders was characterized by large amounts of
      sedentary time and low fulfillment of physical activity guidelines. There is
      therefore a large treatment potential for this group by increasing exercise. The
      results suggest that instead of focusing exclusively on high intensity exercise
      for treating depressive and anxiety disorders, health care providers might
      encourage patients to reduce sedentary time by increasing light physical activity
      and decreasing the number of sedentary bouts, though further studies are needed
      that can determine directionality.

PMID- 25585125
TI  - Phosphonate Emerging Zinc Binding Group in Matrix Metalloproteinase Inhibitors.
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases, capable to
      degrade the extracellular matrix (ECM) in physiologic conditions. Because of
      their overexpression and pivotal role in many pathological events, they have been
      proposed as a therapeutic and prognostic target for a number of diseases.
      Selectivity among MMPs is essential for realizing the clinical potential of
      inhibitors. The design of MMP inhibitors (MMPIs) has largely focused on
      development of various compounds containing a zinc binding group (ZBG) in their
      structure, with hydroxamate being the most potent one. Due to the high degree of
      homology in the catalytic domain of all the MMPs, the specificity and selectivity
      of first generation hydroxamate MMPIs were minimal, with several off-target
      effects and binding to other metzincins. This review highlights the role of
      phosphonate as ZBG in the design and development of new MMPIs. 

PMID- 25585126
TI  - ROS-mediated DNA methylation pattern alterations in carcinogenesis.
AB  - Elevated levels of both reactive oxygen species (ROS) and DNA methylation are
      characteristic of various types of cancer cells. However, the relation between
      these two is not well understood. Here we will discuss the cause-consequence
      relationship between ROS and DNA methylation. Cancer research reveals that
      disregulation of DNA methylation results in regional CpG island hypermethylation
      and generalized genomic hypomethylation. ROS-induced oxidative stress is
      associated with both aberrant hypermethylation of tumor suppressor gene (TSG)
      promoter regions and global hypomethylation. The DNA oxidation structure, 8
      hydroxy-2'-deoxyguanosine (8-OHdG), can induce DNA hypomethylation by inhibiting
      DNA methylation at nearby cytosine bases, while another DNA oxidation structure,
      5-hydroxymethylcytosine (5hmC), may achieve active DNA demethylation processes,
      thus, causing DNA hypomethylation. Recently, it has been found that ROS can
      function as catalysts of DNA methylation, further accounting for TSG promoter
      hypermethylation. Moreover, ROS may induce site-specific hypermethylation via
      either the up-regulation of expression of DNA methyltransferases (DNMTs) or the
      formation of a new DNMT containing complex. In addition, these ROS-induced DNA
      methylation pattern alterations have been implicated with not only malignant
      transformation, but also the progression of numerous tumors. In conclusion, ROS
      can influence both aspects of DNA methylation changes through different
      mechanisms, which play an important role of epigenetic regulation in cancer
      cells. Therefore, the comprehension of mechanisms leading to epigenetic
      modifications associated with ROS may help better understand the carcinogenesis
      and progression, as well as aid in the development of potential biomarkers for
      better cancer diagnostics and novel therapeutic strategies. 

PMID- 25585128
TI  - Withdrawn: Architectural Clones in Aplastic Anaemia- Lessons Learned from High
      Throughput Sequencing.
AB  - Withdrawn by the publisher.

PMID- 25585127
TI  - Ischemic colitis: current diagnosis and treatment.
AB  - Ischemic colitis (CI) is a common form of ischemic injury, which evolves as a
      consequence of decreased arterial blood flow to the colon. In general, CI is
      attributed to an elderly with multiple comorbidities; however, it may also occur
      in young or middle-aged individuals. The etiology of CI is multifactorial and the
      clinical presentation varies upon the severity of deprivation of the intestinal
      blood flow, and the development of the microvasculature plexus. Multiple case
      reports have associations with medications, vascular disorders, pathogens and
      hematologic diseases. Occlusive and nonocclusive diseases are the major
      mechanisms, which are simultaneously the causative factor of intestinal ischemia.
      In this review, we discuss major factors predisposing to occurrence of CI and
      analyze the mechanisms of action of several classes of medications currently
      used. We also suggest possible therapies and discuss the latest reports, which
      may lead to the discovery of novel pharmacological targets for future anti-CI
      drugs to be used in the clinical treatment. 

PMID- 25585129
TI  - Novel identification of matrix proteins involved in calcitic biomineralization.
AB  - Calcitic biomineralization is essential for otoconia formation in vertebrates.
      This process is characterized by protein-crystal interactions that modulate
      crystal growth on an extracellular matrix. An excellent model for the study of
      calcitic biomineralization is the avian eggshell, the fastest known
      biomineralization process. The objective of this study is to identify and
      characterize matrix proteins associated with the eggshell mammillary cones, which
      are hypothesized to regulate the earliest stage of eggshell calcification.
      Mammillary cones were isolated from 2 models, fertilized and unfertilized, and
      the released proteins were identified by RP-nanoLC and ES-MS/MS proteomics.
      Proteomics analysis identified 49 proteins associated with the eggshell membrane
      fibers and, importantly, 18 mammillary cone-specific proteins with an additional
      18 proteins identified as enriched in the mammillary cones. Among the most
      promising candidates for modulating protein-crystal interactions were
      extracellular matrix proteins, including ABI family member 3 (NESH) binding
      protein (ABI3BP), tiarin-like, hyaluronan and proteoglycan link protein 3
      (HAPLN3), collagen alpha-1(X), collagen alpha-1(II) and fibronectin, in addition
      to the calcium binding proteins calumenin, EGF-like repeats and discoidin 1-like
      domains 3 (EDIL3), nucleobindin-2 and SPARC. In conclusion, we identified several
      cone-resident proteins that are candidates to regulate initiation of eggshell
      calcification. Further study of these proteins will determine their roles in
      modulating calcitic biomineralization and lead to insight into the process of
      otoconia formation/regeneration. BIOLOGICAL SIGNIFICANCE: Biomineralization is
      essential for the development of hard tissues in vertebrates, which includes both
      calcium phosphate and calcium carbonate structures. Calcitic mineralization by
      calcium carbonate is an important process in the formation of otoconia, which are
      gravity receptor organs located in the inner ear and are responsible for balance
      and for sensing linear acceleration. Deficiencies in the regulation of their
      biomineralization can lead to otoconia degeneration and eventually benign
      paroxysmal position vertigo (BPPV), which is the main cause of vertigo in humans.
      Eggshell formation in chicken is one of the fastest known biomineralization
      processes and is an excellent model for the study of calcitic biomineralization.
      Cross-analysis of proteomic data from two mineralized models, fertilized and
      unfertilized chicken eggshells, identified proteins associated with the
      mammillary cones that are the sites of initiation of eggshell formation. We
      hypothesize that these proteins regulate the earliest stages of eggshell
      calcification. The human homologs of these proteins are therefore potential
      candidates to play a role in otoconia biomineralization.

PMID- 25585130
TI  - Combinatorial Peptide Ligand Library and two dimensional electrophoresis: new
      frontiers in the study of peritoneal dialysis effluent in pediatric patients.
AB  - Peritoneal dialysis effluent (PDE) is a fluid resulting from the close contact of
      peritoneal dialysis (PD) solutions with the peritoneal membrane (PM) and
      represents a readily available material for the search of biomarkers of PM
      function or damage. Our laboratory has developed a method for the in-depth
      proteomic characterization of PDE, which involves Combinatorial Peptides Ligand
      Library (CPLL) to reduce the dynamic range of protein concentration in PDE,
      followed by two-dimensional electrophoresis (2-DE). In this study we applied this
      method to the analysis of PDE proteome obtained from 19 pediatric patients on
      automated peritoneal dialysis (APD) with glucose-based PD solutions. The combined
      use of this proteomic approach highlighted a mean of 700 new proteins.
      Differences in PDE proteome profile were observed in relation with the duration
      of APD treatment. In particular, in patients on long-term APD, we observed an
      increase of intelectin-1, and a decrease of gelsolin. These changes were also
      observed by in vitro treatment of mesothelial cells with oxidative or pro
      fibrotic stimulus which supported the biological role of these proteins' changes.
      In order to clarify the biological meaning of the observed differences, further
      step of our study will consist of the longitudinal evaluation of PDE proteome.
      BIOLOGICAL SIGNIFICANCE: The in-depth proteomic characterization of peritoneal
      dialysis effluent (PDE) in pediatric patients by the combined use of
      Combinatorial Peptide Ligand Library (CPLL) and two dimensional electrophoresis
      allowed to detect 1788 spots, a relevant part (724) of which were previously
      undetected in sample untreated with CPLL. In patients on long-term automated
      peritoneal dialysis, this proteomic approach allowed to identify 29 potential
      biomarkers that could be of help to identify patients with subclinical
      inflammation and/or developing peritoneal membrane fibrosis, thus adapting
      dialysis treatment accordingly.

PMID- 25585132
TI  - Dynamic measurement of extracellular opioid activity: status quo, challenges, and
      significance in rewarded behaviors.
AB  - Opioid peptides are the endogenous ligands of opioid receptors, which are also
      the molecular target of naturally occurring and synthetic opiates, such as
      morphine and heroin. Since their discovery in the 1970s, opioid peptides, which
      are found widely throughout the central nervous system and the periphery, have
      been intensely studied because of their involvement in pain and pleasure. Over
      the years, our understanding of opioid peptides has widened to cover a multitude
      of functions, including learning and memory, affective state, gastrointestinal
      transit, feeding, immune function, and metabolism. Unsurprisingly, aberrant
      opioid activity is implicated in numerous pathologies, including drug addiction,
      overeating, pain, depression, and obesity. To date, virtually all preclinical and
      clinical studies aimed at understanding the function of endogenous opioids have
      relied upon manipulating endogenous opioid fluxes using opioid receptor ligands
      or genetic manipulations of opioid receptors and endogenous opioids. Difficulties
      in directly monitoring endogenous opioid fluxes, particularly in the central
      nervous system, have presented a major obstacle to fully understanding endogenous
      opioid function. This review summarizes these challenges and offers suggestions
      for future goals while focusing on the neurobiology of reward, specifically
      drawing attention to studies that have succeeded in dynamically measuring opioid
      peptides.

PMID- 25585131
TI  - The association between individual income and aggressive end-of-life treatment in
      older cancer decedents in Taiwan.
AB  - OBJECTIVES: To examine the association of individual income and end of life (EOL)
      care in older cancer decedents in Taiwan. DESIGN: Retrospective cohort study.
      SETTING: National Health Insurance Research Database (NHIRD) in Taiwan.
      PARTICIPANTS: 28,978 decedents >65 years were diagnosed with cancer and died
      during 2009-2011 in Taiwan. Of these decedents, 10941, 16535, and 1502 were
      categorized by individual income as having low, moderate, and high SES,
      respectively. MAIN OUTCOME MEASURES: Indicators of aggressiveness of EOL care:
      chemotherapy use before EOL, more than one emergency department (ER) visit, more
      than one hospital admission, hospital length of stay >14 days, intensive care
      unit (ICU) admission, and dying in a hospital. RESULTS: Low individual income was
      associated with more aggressive EOL treatment (estimate -0.30 for moderate
      income, -0.27 for high income, both p<0.01). The major source of aggressiveness
      was the tendency for older decedents with low income to die in the acute care
      hospital. The indicators had an increasing trend from 2009 to 2011, except for
      hospital stay >14 days. CONCLUSIONS: Low individual income is associated with
      more aggressive EOL treatment in older cancer decedents. Public health providers
      should make available appropriate education and hospice resources to these
      decedents and their families, to reduce the amount of aggressive terminal care
      such decedents receive.

PMID- 25585133
TI  - Investigation of drug-excipient interactions in lapatinib amorphous solid
      dispersions using solid-state NMR spectroscopy.
AB  - This study investigated the presence of specific drug-excipient interactions in
      amorphous solid dispersions of lapatinib (LB) and four commonly used
      pharmaceutical polymers, including Soluplus, polyvinylpyrrolidone vinyl acetate
      (PVPVA), hydroxypropylmethylcellulose acetate succinate (HPMCAS), and
      hydroxypropylmethylcellulose phthalate (HPMCP). Based on predicted pKa
      differences, LB was hypothesized to exhibit a specific ionic interaction with
      HPMCP, and possibly with HPMCAS, while Soluplus and PVPVA were studied as
      controls without ionizable functionality. Thermal studies showed a single glass
      transition (Tg) for each dispersion, in close agreement with predicted values for
      Soluplus, PVPVA, and HPMCAS systems. However, the Tg values of LB-HPMCP solid
      dispersions were markedly higher than predicted values, indicating a strong
      intermolecular interaction between LB and HPMCP. (15)N solid-state NMR provided
      direct spectroscopic evidence for protonation of LB (i.e., salt formation) within
      the HPMCP solid dispersions. (1)H T1 and (1)H T1rho relaxation studies of the
      dispersions supported the ionic interaction hypothesis, and indicated multiple
      phases in the cases of excess drug or polymer. In addition, the dissolution and
      stability behavior of each system was examined. Both acidic polymers, HPMCAS and
      HPMCP, effectively inhibited the crystallization of LB on accelerated stability,
      likely owing to beneficial strong intermolecular hydrogen and/or specific ionic
      bonds with the acidic polymers. Soluplus and PVPVA showed poor physical
      properties on stability and subsequently poor crystallization inhibition. 

PMID- 25585134
TI  - Ocular drug delivery nanowafer with enhanced therapeutic efficacy.
AB  - Presently, eye injuries are treated by topical eye drop therapy. Because of the
      ocular surface barriers, topical eye drops must be applied several times in a
      day, causing side effects such as glaucoma, cataract, and poor patient
      compliance. This article presents the development of a nanowafer drug delivery
      system in which the polymer and the drug work synergistically to elicit an
      enhanced therapeutic efficacy with negligible adverse immune responses. The
      nanowafer is a small transparent circular disc that contains arrays of drug
      loaded nanoreservoirs. The slow drug release from the nanowafer increases the
      drug residence time on the ocular surface and its subsequent absorption into the
      surrounding ocular tissue. At the end of the stipulated period of drug release,
      the nanowafer will dissolve and fade away. The in vivo efficacy of the axitinib
      loaded nanowafer was demonstrated in treating corneal neovascularization (CNV) in
      a murine ocular burn model. The laser scanning confocal imaging and RT-PCR study
      revealed that once a day administered axitinib nanowafer was therapeutically
      twice as effective, compared to axitinib delivered twice a day by topical eye
      drop therapy. The axitinib nanowafer is nontoxic and did not affect the wound
      healing and epithelial recovery of the ocular burn induced corneas. These results
      confirmed that drug release from the axitinib nanowafer is more effective in
      inhibiting CNV compared to the topical eye drop treatment even at a lower dosing
      frequency. 

PMID- 25585135
TI  - Biophysical properties of acid-sensing ion channels (ASICs).
AB  - Acid-sensing ion channels (ASICs) are ligand-gated ion channels that are
      exquisitely sensitive to extracellular protons and can sense transient as well as
      sustained acidification. In this review, we will discuss activation and
      desensitization of ASICs by protons. We show that a linear reaction scheme can
      reproduce the basic electrophysiological properties of ASICs, including steady
      state desensitization. Moreover, we will discuss how a desensitizing receptor can
      sense sustained acidosis and what we know about the putative proton sensor. We
      will briefly discuss modulation of proton gating by neuropeptides and small
      positively charged ligands. Finally, we will review the pore properties of ASICs
      and their relation to the recently reported crystal structure of the open ASIC
      pore. This article is part of the Special Issue entitled 'Acid-Sensing Ion
      Channels in the Nervous System'. 

PMID- 25585138
TI  - Deep sleep after social stress: NREM sleep slow-wave activity is enhanced in both
      winners and losers of a conflict.
AB  - Sleep is considered to be a recovery process of prior wakefulness. Not only
      duration of the waking period affects sleep architecture and sleep EEG, the
      quality of wakefulness is also highly important. Studies in rats have shown that
      social defeat stress, in which experimental animals are attacked and defeated by
      a dominant conspecific, is followed by an acute increase in NREM sleep EEG slow
      wave activity (SWA). However, it is not known whether this effect is specific for
      the stress of social defeat or a result of the conflict per se. In the present
      experiment, we examined how sleep is affected in both the winners and losers of a
      social conflict. Sleep-wake patterns and sleep EEG were recorded in male wild
      type Groningen rats that were subjected to 1h of social conflict in the middle of
      the light phase. All animals were confronted with a conspecific of similar
      aggression level and the conflict took place in a neutral arena where both
      individuals had an equal chance to either win or lose the conflict. NREM sleep
      SWA was significantly increased after the social conflict compared to baseline
      values and a gentle stimulation control condition. REM sleep was significantly
      suppressed in the first hours after the conflict. Winners and losers did not
      differ significantly in NREM sleep time, NREM sleep SWA and REM sleep time
      immediately after the conflict. Losers tended to have slightly more NREM sleep
      later in the recovery period. This study shows that in rats a social conflict
      with an unpredictable outcome has quantitatively and qualitatively largely
      similar acute effects on subsequent sleep in winners and losers. 

PMID- 25585139
TI  - The effects of household management practices on the global warming potential of
      urban lawns.
AB  - Nitrous oxide (N2O) emissions are an important component of the greenhouse gas
      (GHG) budget for urban turfgrasses. A biogeochemical model DNDC successfully
      captured the magnitudes and patterns of N2O emissions observed at an urban
      turfgrass system at the Richland Creek Watershed in Nashville, TN. The model was
      then used to study the long-term (i.e. 75 years) impacts of lawn management
      practice (LMP) on soil organic carbon sequestration rate (dSOC), soil N2O
      emissions, and net Global Warming Potentials (net GWPs). The model simulated N2O
      emissions and net GWP from the three management intensity levels over 75 years
      ranged from 0.75 to 3.57 kg N ha(-1)yr(-1) and 697 to 2443 kg CO2-eq ha(-1)yr(
      1), respectively, which suggested that turfgrasses act as a net carbon emitter.
      Reduction of fertilization is most effective to mitigate the global warming
      potentials of turfgrasses. Compared to the baseline scenario, halving
      fertilization rate and clipping recycle as an alternative to synthetic fertilizer
      can reduce net GWPs by 17% and 12%, respectively. In addition, reducing
      irrigation and mowing are also effective in lowering net GWPs. The minimum
      maintenance LMP without irrigation and fertilization can reduce annual N2O
      emissions and net GWPs by approximately 53% and 70%, respectively, with the price
      of gradual depletion of soil organic carbon, when compared to the intensive
      maintenance LMP. A lawn age-dependent best management practice is recommended: a
      high dose fertilizer input at the initial stage of lawn establishment to enhance
      SOC sequestration, followed by decreasing fertilization rate when the lawn ages
      to minimize N2O emissions. A minimum-maintained LMP with clipping recycling, and
      minimum irrigation and mowing, is recommended to mitigate global warming effects
      from urban turfgrass systems. Among all practices, clipping recycle may be a
      relatively malleable behavior and, therefore, a good target for interventions
      seeking to reduce the environmental impacts of lawn management through public
      education. Our results suggest that a long-term or a chronosequence study of
      turfgrasses with varying ages is warranted to capture the complete dynamics of
      contribution of turfgrasses to global warming.

PMID- 25585137
TI  - Resolvins AT-D1 and E1 differentially impact functional outcome, post-traumatic
      sleep, and microglial activation following diffuse brain injury in the mouse.
AB  - Traumatic brain injury (TBI) is induced by mechanical forces which initiate a
      cascade of secondary injury processes, including inflammation. Therapies which
      resolve the inflammatory response may promote neural repair without exacerbating
      the primary injury. Specific derivatives of omega-3 fatty acids loosely grouped
      as specialized pro-resolving lipid mediators (SPMs) and termed resolvins promote
      the active resolution of inflammation. In the current study, we investigate the
      effect of two resolvin molecules, RvE1 and AT-RvD1, on post-traumatic sleep and
      functional outcome following diffuse TBI through modulation of the inflammatory
      response. Adult, male C57BL/6 mice were injured using a midline fluid percussion
      injury (mFPI) model (6-10min righting reflex time for brain-injured mice).
      Experimental groups included mFPI administered RvE1 (100ng daily), AT-RvD1 (100ng
      daily), or vehicle (sterile saline) and counterbalanced with uninjured sham mice.
      Resolvins or saline were administered daily for seven consecutive days beginning
      3days prior to TBI to evaluate proof-of-principle to improve outcome. Immediately
      following diffuse TBI, post-traumatic sleep was recorded for 24h post-injury. For
      days 1-7 post-injury, motor outcome was assessed by rotarod. Cognitive function
      was measured at 6days post-injury using novel object recognition (NOR). At 7days
      post-injury, microglial activation was quantified using immunohistochemistry for
      Iba-1. In the diffuse brain-injured mouse, AT-RvD1 treatment, but not RvE1,
      mitigated motor and cognitive deficits. RvE1 treatment significantly increased
      post-traumatic sleep in brain-injured mice compared to all other groups. RvE1
      treated mice displayed a higher proportion of ramified microglia and lower
      proportion of activated rod microglia in the cortex compared to saline or AT-RvD1
      treated brain-injured mice. Thus, RvE1 treatment modulated post-traumatic sleep
      and the inflammatory response to TBI, albeit independently of improvement in
      motor and cognitive outcome as seen in AT-RvD1-treated mice. This suggests AT
      RvD1 may impart functional benefit through mechanisms other than resolution of
      inflammation alone. 

PMID- 25585140
TI  - Implications of leading crop production practices on environmental quality and
      human health.
AB  - Globally, much weight is currently being placed on agriculture to provide food
      for the growing population as well as feedstock for the bioenergy industry.
      Unfortunately, the intensification of agricultural operations to satisfy these
      growing needs has been associated with a number of environmental and human health
      risks. A review of publications on the subject was conducted and emphasis was
      placed on articles focusing on agriculture, environment, and public health as
      well as their interactions. Supporting information was also gathered from
      publications of various agricultural and environmental agencies. Agricultural
      practices with potential negative implications on the environment and human
      health were identified broadly as: (a) utilization of biosolids and animal
      manures, (b) use of agricultural chemicals, (c) management of post-harvest
      residue, (d) irrigation, and (e) tillage operations. Soil, water, and air
      contamination by nutrients, heavy metals, pathogens, and pesticides, as well as
      air contamination by particulate matters, noxious gases, and pathogens were among
      the leading environmental impacts. Some of the human-health impacts identified
      included neurological and reproductive defects, cardiovascular risks, cancers and
      other diseases (of kidney, liver, lung, and skin), skin allergies,
      gastroenteritis, and methemoglobinemia. Continual awareness on the impacts of the
      reviewed agricultural practices on environmental quality and human health and the
      implementation of experimentally-backed best management practices in agricultural
      systems remain indispensable. 

PMID- 25585141
TI  - Development of a benthic diatom index of biotic integrity (BD-IBI) for ecosystem
      health assessment of human dominant subtropical rivers, China.
AB  - As efforts intensify to address the issues of declining water quality and
      biodiversity losses in freshwater ecosystems, there have been great demands for
      effective methods of evaluating aquatic ecosystem health. In this study, benthic
      algae assemblages and water quality variables were analyzed to develop a benthic
      diatom-based index of biotic integrity (BD-IBI) for assessment of the aquatic
      environment in the upper Han River (China). Through the use of multivariate and
      multimetric approaches, four metrics - % prostrate individuals, % Amphora
      individuals, % polysaprob species, and diatom-based eutrophication/pollution
      index (EPI-D) - were identified from 98 candidate metrics to develop a BD-IBI.
      Application of the index revealed that water quality in 11% of the 31 sampled
      sites could be described as excellent condition, in 43% of the sites it could be
      described as good condition, in 25% as moderate condition, and in 21% as poor
      condition. The assessment further revealed that the main reason for degradation
      of the Han river ecosystem was nutrient enrichment through agricultural land use.

PMID- 25585142
TI  - A new morphological approach for removing acid dye from leather waste water:
      preparation and characterization of metal-chelated spherical particulated
      membranes (SPMs).
AB  - In this study, p(HEMA-GMA) poly(hydroxyethyl methacrylate-co-glycidyl
      methacrylate) spherical particulated membranes (SPMs) were produced by UV
      photopolymerization and the synthesized SPMs were coupled with iminodiacetic acid
      (IDA). Finally the novel SPMs were chelated with Cr(III) ions as ligand and used
      for removing acid black 210 dye. Characterizations of the metal-chelated SPMs
      were made by SEM, FTIR and swelling test. The water absorption capacities and
      acid dye adsorption properties of the SPMs were investigated and the results were
      245.0, 50.0, 55.0 and 51.9% for p(HEMA), p(HEMA-GMA), p(HEMA-GMA)-IDA and p(HEMA
      GMA)-IDA-Cr(III) SPMs respectively. Adsorption properties of the p(HEMA-GMA)-IDA
      Cr(III) SPMs were investigated under different conditions such as different
      initial dye concentrations and pH. The optimum pH was observed at 4.3 and the
      maximum adsorption capacity was determined as 885.14 mg/g at about 8000 ppm
      initial dye concentration. The concentrations of the dyes were determined using a
      UV/Vis Spectrophotometer at a wavelength of 435 nm. Reusability of p(HEMA-GMA)
      IDA-Cr(III) SPMs was also shown for five adsorption-desorption cycles without
      considerable decrease in its adsorption capacity. Finally, the results showed
      that the metal-chelated p(HEMA-GMA)-IDA SPMs were effective sorbent systems
      removing acid dye from leather waste water.

PMID- 25585143
TI  - Equilibrium and kinetics studies on As(V) and Sb(V) removal by Fe2+ -doped Mg-Al
      layered double hydroxides.
AB  - Mg-Al layered double hydroxides (Mg-Al LDHs) doped with Fe(2+) adsorbed As(V)
      [Formula: see text] and Sb(V) [Formula: see text] from an aqueous solution
      through anion exchange with Cl(-) intercalated in the LDH interlayer. Fe(2+)
      doped Mg-Al LDH exhibited superior As(V) removal compared with Mg-Al LDH. The
      oxidation of Fe(2+) doped in the Mg-Al LDH host layer to Fe(3+) increased the
      positive layer charge of the LDH, thus increasing the anion-uptake capacity owing
      to stronger electrostatic attractive force between the positively charged layer
      and the anion. However, Fe(2+)-doped Mg-Al LDH was not superior to Mg-Al LDH in
      terms of Sb(V) removal. This was attributed to the preferential intercalation of
      OH(-) over [Formula: see text] . The As(V) and Sb(V) removal by LDH followed
      Langmuir-type adsorption, which proceeded via a pseudo-first-order reaction. The
      equilibrium and kinetics studies confirm that the adsorption of As(V) and Sb(V)
      by Fe(2+)-doped Mg-Al LDH was the result of chemical adsorption, involving the
      anion exchange of [Formula: see text] and [Formula: see text] with the
      intercalated Cl(-). 

PMID- 25585144
TI  - Dynamics of organic matter, nitrogen and phosphorus removal and their
      interactions in a tidal operated constructed wetland.
AB  - This paper demonstrates the potential of tidal flow operated constructed wetland
      application for the removal dynamics of organic matter, nitrogen and phosphorus.
      Near-complete removal of organic matter was achieved with a constant removal
      efficiency of 95%, irrespective of TOC influent loadings ranged from 10 g/m(2) .
      d to 700 g/m(2) . d. High NH4(+)-N removal at 95% efficiency under influent
      loading of 17 g/m(2) . d, was stably obtained and was not negatively influenced
      by increasing influent organic carbon loading rate. Increased influent TOC
      loading (350 g/m(2) . d to 700 g/m(2) . d) significantly enhanced denitrification
      capacity and increased TN removal from 30% to 95%. Under tidal flow operation, a
      higher carbon supply (C/N = 20) for complete TN removal was demonstrated as
      comparing to that observed in traditional CWs approaches. In addition, the
      removal of phosphorus was strongly influenced by organic loadings. However,
      further investigations are needed to elucidate the detailed mechanism that would
      explain the role of organic loading in phosphorus removal.

PMID- 25585145
TI  - Predicting fecal sources in waters with diverse pollution loads using general and
      molecular host-specific indicators and applying machine learning methods.
AB  - In this study we use a machine learning software (Ichnaea) to generate predictive
      models for water samples with different concentrations of fecal contamination
      (point source, moderate and low). We applied several MST methods (host-specific
      Bacteroides phages, mitochondrial DNA genetic markers, Bifidobacterium
      adolescentis and Bifidobacterium dentium markers, and bifidobacterial host
      specific qPCR), and general indicators (Escherichia coli, enterococci and somatic
      coliphages) to evaluate the source of contamination in the samples. The results
      provided data to the Ichnaea software, that evaluated the performance of each
      method in the different scenarios and determined the source of the contamination.
      Almost all MST methods in this study determined correctly the origin of fecal
      contamination at point source and in moderate concentration samples. When the
      dilution of the fecal pollution increased (below 3 log10 CFU E. coli/100 ml) some
      of these indicators (bifidobacterial host-specific qPCR, some mitochondrial
      markers or B. dentium marker) were not suitable because their concentrations
      decreased below the detection limit. Using the data from source point samples,
      the software Ichnaea produced models for waters with low levels of fecal
      pollution. These models included some MST methods, on the basis of their best
      performance, that were used to determine the source of pollution in this area.
      Regardless the methods selected, that could vary depending on the scenario,
      inductive machine learning methods are a promising tool in MST studies and may
      represent a leap forward in solving MST cases.

PMID- 25585146
TI  - Arsenic and antimony in water and wastewater: overview of removal techniques with
      special reference to latest advances in adsorption.
AB  - Arsenic and antimony are metalloids, naturally present in the environment but
      also introduced by human activities. Both elements are toxic and carcinogenic,
      and their removal from water is of unquestionable importance. The present article
      begins with an overview of As and Sb chemistry, distribution and toxicity, which
      are relevant aspects to understand and develop remediation techniques. A brief
      review of the recent results in analytical methods for speciation and
      quantification was also provided. The most common As and Sb removal techniques
      (coagulation/flocculation, oxidation, membrane processes, electrochemical methods
      and phyto and bioremediation) are presented with discussion of their advantages,
      drawbacks and the main recent achievements. Literature review on adsorption and
      biosorption were focused in detail. Considering especially the case of developing
      countries or rural communities, but also the finite energy resources that over
      the world are still dependent, recent research have focused especially readily
      available low-cost adsorbents, as minerals, wastes and biosorbents. Many of these
      alternative sorbents have been presenting promising results and can be even
      superior when compared to the commercial ones. Sorption capacities were
      accurately compiled for As(III,V) and Sb(III,V) species in order to provide to
      the reader an easy but detailed comparison. Some aspects related to experimental
      conditions, comparison criteria, lack of research studies, economic aspects and
      adsorption mechanisms were critically discussed. 

PMID- 25585147
TI  - Forecasting cyanobacteria dominance in Canadian temperate lakes.
AB  - Predictive models based on broad scale, spatial surveys typically identify
      nutrients and climate as the most important predictors of cyanobacteria
      abundance; however these models generally have low predictive power because at
      smaller geographic scales numerous other factors may be equally or more
      important. At the lake level, for example, the ability to forecast cyanobacteria
      dominance is of tremendous value to lake managers as they can use such models to
      communicate exposure risks associated with recreational and drinking water use,
      and possible exposure to algal toxins, in advance of bloom occurrence. We used
      detailed algal, limnological and meteorological data from two temperate lakes in
      south-central Ontario, Canada to determine the factors that are closely linked to
      cyanobacteria dominance, and to develop easy to use models to forecast
      cyanobacteria biovolume. For Brandy Lake (BL), the strongest and most
      parsimonious model for forecasting % cyanobacteria biovolume (% CB) included
      water column stability, hypolimnetic TP, and % cyanobacteria biovolume two weeks
      prior. For Three Mile Lake (TML), the best model for forecasting % CB included
      water column stability, hypolimnetic TP concentration, and 7-d mean wind speed.
      The models for forecasting % CB in BL and TML are fundamentally different in
      their lag periods (BL = lag 1 model and TML = lag 2 model) and in some predictor
      variables despite the close proximity of the study lakes. We speculate that three
      main factors (nutrient concentrations, water transparency and lake morphometry)
      may have contributed to differences in the models developed, and may account for
      variation observed in models derived from large spatial surveys. Our results
      illustrate that while forecast models can be developed to determine when
      cyanobacteria will dominate within two temperate lakes, the models require
      detailed, lake-specific calibration to be effective as risk-management tools.

PMID- 25585148
TI  - Removal of glyphosate herbicide from water using biopolymer membranes.
AB  - Enormous amounts of pesticides are manufactured and used worldwide, some of which
      reach soils and aquatic systems. Glyphosate is a non-selective herbicide that is
      effective against all types of weeds and has been used for many years. It can
      therefore be found as a contaminant in water, and procedures are required for its
      removal. This work investigates the use of biopolymeric membranes prepared with
      chitosan (CS), alginate (AG), and a chitosan/alginate combination (CS/AG) for the
      adsorption of glyphosate present in water samples. The adsorption of glyphosate
      by the different membranes was investigated using the pseudo-first order and
      pseudo-second order kinetic models, as well as the Langmuir and Freundlich
      isotherm models. The membranes were characterized regarding membrane solubility,
      swelling, mechanical, chemical and morphological properties. The results of
      kinetics experiments showed that adsorption equilibrium was reached within 4 h
      and that the CS membrane presented the best adsorption (10.88 mg of glyphosate/g
      of membrane), followed by the CS/AG bilayer (8.70 mg of glyphosate/g of
      membrane). The AG membrane did not show any adsorption capacity for this
      herbicide. The pseudo-second order model provided good fits to the glyphosate
      adsorption data on CS and CS/AG membranes, with high correlation coefficient
      values. Glyphosate adsorption by the membranes could be fitted by the Freundlich
      isotherm model. There was a high affinity between glyphosate and the CS membrane
      and moderate affinity in the case of the CS/AG membrane. Physico-chemical
      characterization of the membranes showed low values of solubility in water,
      indicating that the membranes are stable and not soluble in water. The SEM and
      AFM analysis showed evidence of the presence of glyphosate on CS membranes and on
      chitosan face on CS/AG membranes. The results showed that the glyphosate
      herbicide can be adsorbed by chitosan membranes and the proposed membrane-based
      methodology was successfully used to treat a water sample contaminated with
      glyphosate. Biopolymer membranes therefore potentially offer a versatile method
      to eliminate agricultural chemicals from water supplies.

PMID- 25585149
TI  - Storage management influences greenhouse gas emissions from biosolids.
AB  - Biosolids produced by wastewater treatment plants are often stored in stockpiles
      and can be a significant source of greenhouse gases (GHG). Growing trees in
      shallow stockpiled biosolids may remove nutrients, keep the biosolids drier and
      offset GHG emissions through C sequestration. We directly measured methane (CH4),
      carbon dioxide (CO2) and nitrous oxide (N2O) flux from a large biosolid stockpile
      and two shallow stockpiles, one planted with Salix reichardtii (willow) trees,
      from December 2009 to January 2011. All stockpiles emitted large annual amounts
      of GHG ranging from 38 kg CO2-e Mg(-1) dry biosolid for the large stockpile, to
      65 kg CO2-e Mg(-1) for the unplanted shallow stockpile, probably due to the
      greater surface area to volume ratio. GHG emissions were dominated by N2O and CO2
      whilst CH4 emissions were negligible (<2%) from the large stockpile and the
      shallow stockpiles were actually a CH4 sink. Annual willow tree growth was 12 Mg
      dry biomass ha(-1), but this only offset 8% of the GHG emissions from the shallow
      planted stockpile. Our data highlight that biosolid stockpiles are significant
      sources for GHG emissions but alternate management options such as shallow
      stockpiles or planting for biomass production will not lead to GHG emission
      reductions.

PMID- 25585150
TI  - A review on the effects of PBDEs on thyroid and reproduction systems in fish.
AB  - The objective of this review was to summarize and discuss the effects of
      Polybrominated diphenyl ethers (PBDEs) on thyroid and reproduction systems in
      fish. We reviewed the evidences and mechanisms for PBDEs-induced thyroid and
      reproduction disruption, as well as the cross-talk between the two systems in
      fish. In thyroid disruption, we mainly paid attention to the effects of PBDEs on
      hypothalamic-pituitary-thyroid (HPT) axis, thyroid hormones (THs) transport and
      metabolism, thyroid receptors (TRs) and thyroid follicle histology. In
      reproduction disruption, we focused on the effects of PBDEs on steroid hormone
      production, expression of genes involved in steroidogenesis, and gonadal
      development. Despite that there is an interaction between thyroid and
      reproductive systems in fish, it is still remains unclear that PBDE-induced
      reproductive impairments are caused by direct effects on hypothalamic-pituitary
      gonadal (HPG) functioning or by indirect action through cross-talk between the
      two systems. Future studies are needed to explore the relationships between
      reproductive toxicity and thyroid system disruption after PBDEs exposure. 

PMID- 25585151
TI  - Curtailing the hydroxylaminobarbituric acid-hydantoin rearrangement to favor HNO
      generation.
AB  - Due to its inherent reactivity, HNO must be generated in situ through the use of
      donor compounds. One of the primary strategies for the development of new HNO
      donors has been modifying hydroxylamines with good leaving groups. A recent
      example of this strategy is the (hydroxylamino)barbituric acid (HABA) class of
      HNO donors. In this case, however, an undesired intramolecular rearrangement
      pathway to the corresponding hydantoin derivative competes with HNO formation,
      particularly in the absence of chemical traps for HNO. This competitive non-HNO
      producing pathway has restricted the development of the HABA class to examples
      with fast HNO release profiles at physiological pH and temperature (t(1/2) < 1
      min). Herein, the factors that favor the rearrangement pathway have been examined
      and two independent strategies that protect against rearrangement to favor HNO
      generation have been developed. The timecourse and stoichiometry for the in vitro
      conversion of these compounds to HNO (trapped as a phosphine aza-ylide) and the
      corresponding barbituric acid (BA) byproduct have been determined by (1)H NMR
      spectroscopy under physiologically relevant conditions. These results confirm the
      successful extension of the HABA class of pure HNO donors with half-lives at pH
      7.4, 37  degrees C ranging from 19 to 107 min.

PMID- 25585152
TI  - Monoamine oxidase A inhibitor-near-infrared dye conjugate reduces prostate tumor
      growth.
AB  - Development of anti-cancer agents with high tumor-targeting specificity and
      efficacy is critical for modern multidisciplinary cancer research. Monoamine
      oxidase A (MAOA), a mitochondria-bound enzyme, degrades monoamine
      neurotransmitters and dietary monoamines. Recent evidence suggests a correlation
      between increased MAOA expression and prostate cancer (PCa) progression with poor
      outcomes for patients. MAOA induces epithelial-mesenchymal transition (EMT) and
      augments hypoxic effects by producing excess reactive oxygen species. Thus,
      development of MAOA inhibitors which selectively target tumors becomes an
      important goal in cancer pharmacology. Here we describe the design, synthesis,
      and in vitro and in vivo evaluation of NMI, a conjugate that combines a near
      infrared dye for tumor targeting with the moiety derived from the MAOA inhibitor
      clorgyline. NMI inhibits MAOA with low micromolar IC50, suppresses PCa cell
      proliferation and colony formation, and reduces migration and invasion. In mouse
      PCa xenografts, NMI targets tumors with no detectable accumulation in normal
      tissues, providing effective reduction of the tumor burden. Analysis of tumor
      specimens shows reduction in Ki-67(+) and CD31(+) cells, suggesting a decrease of
      cell proliferation and angiogenesis and an increase in M30(+) cells, indicating
      increased apoptosis. Gene expression profiles of tumors treated with NMI
      demonstrate reduced expression of oncogenes FOS, JUN, NFKB, and MYC and cell
      cycle regulators CCND1, CCNE1, and CDK4/6, along with increases in the levels of
      tumor suppressor gene TP53, cell cycle inhibitors CDKN1A and CDKN2A, and MAOA
      downstream genes that promote EMT, tumor hypoxia, cancer cell migration, and
      invasion. These data suggest that NMI exerts its effect through tumor-targeted
      delivery of a MAOA-inactivating group, making NMI a valuable anti-tumor agent. 

PMID- 25585153
TI  - Chloroplast capture and intra- and inter-continental biogeographic
      diversification in the Asian - New World disjunct plant genus Osmorhiza
      (Apiaceae).
AB  - Osmorhiza Raf. (Apiaceae) contains about 12 species disjunctly distributed in
      temperate Asia, and North, Central to South America. Phylogenetic and
      biogeographic analyses were carried out applying sequences of two nuclear and
      nine plastid loci from eleven recognized Osmorhiza species. The nuclear ITS and
      ETS and the plastid data fully resolved the infrageneric relationships, yet the
      two phylogenies were largely incongruent. Comparisons of nuclear and plastid
      phylogenies revealed several interspecific chloroplast transfer events in
      Osmorhiza, one of which involved an extinct or an unsampled lineage. This genus
      was inferred to have originated in the Old World during the late Miocene
      (11.02mya, 95% HPD: 9.13-12.93mya), and the crown of the genus was dated to be in
      the late Miocene (5.51mya, 95% HPD: 2.81-8.37mya). Species of Osmorhiza were
      inferred to have migrated from the Old World into North America across the Bering
      land bridge during the late Miocene, and they then diversified in the New World
      through multiple dispersal and divergence events. The intraspecific amphitropical
      disjunctions between North and South America, and the eastern and western North
      American disjunctions within O. berteroi and O. depauperata were hypothesized to
      be via recent long-distance dispersals most likely facilitated by birds. 

PMID- 25585154
TI  - Multilocus phylogenetic inference in subfamily Chlorogaloideae and related genera
      of Agavaceae - informing questions in taxonomy at multiple ranks.
AB  - A series of taxonomic questions at the subfamilial, generic, and intrageneric
      levels have remained within subfamily Chlorogaloideae s.s. (comprising Camassia,
      Chlorogalum, Hastingsia, and Schoenolirion) and relatives in Agavaceae. We
      present the first phylogenetic hypotheses focused on Chlorogaloideae that are
      based on multiple independent loci and include a wide sampling of outgroups
      across Agavaceae. In addition to chloroplast regions ndhF and trnL-trnF, we used
      nrDNA ITS for phylogenetic inference. Incomplete concerted evolution of the
      latter is indicated by intra-individual site polymorphisms for nearly half of the
      individuals. Comparisons of four coding and analysis methods for these characters
      indicate that the region remains phylogenetically informative. Our results
      confirm that Chlorogaloideae s.s. is not monophyletic, due to the close
      relationship of Schoenolirion with Hesperaloe and Hesperoyucca, as well as the
      likely sister relationship between Hesperocallis and core Chlorogaloideae
      (Camassia, Chlorogalum, and Hastingsia). Chlorogalum is also not monophyletic,
      being divided with strong support into vespertine and diurnal clades. This study
      produced the first phylogenetic hypotheses across Hesperaloe, allowing initial
      tests of several taxonomic disagreements within this genus. Our results reveal
      the lack of cohesion of H. funifera, indicating that H. funifera ssp. funifera
      may be more closely related to H. campanulata than to H. funifera ssp. chiangii
      (=H. chiangii). With potential gene flow between many members of Hesperaloe and a
      possible hybrid origin for H. campanulata, the genetic relationships within this
      genus appear complex. Further population-level investigation of many of the taxa
      in Chlorogaloideae s.l. would benefit our understanding of the evolution and
      taxonomy of these groups; Camassia and Hastingsia are the current focus of
      ongoing study. 

PMID- 25585155
TI  - Serum levels of persistent organic pollutants and predictors of exposure in
      Tunisian women.
AB  - INTRODUCTION: In spite of the international consensus on the human health risks
      associated with exposure to persistent organic pollutants (POPs), the Tunisian
      population is suspected to have been inadvertently exposed to POPs over the last
      decades. OBJECTIVES: The aim of this study was to evaluate POP concentrations in
      the serum of a subset of 54 Tunisian women and to identify some socio-demographic
      and dietary predictors of exposure to POPs. RESULTS: Of the ten POPs analyzed,
      three polychlorinated biphenyl (PCB) congeners (-138, -153 and -180), and two
      organochlorine pesticides (OCPs), HCB and p,p'-DDE, showed frequencies ranging
      from 98 to 100%. Serum median concentrations of PCB congeners (-138, -153 PCB
      180) were 26.08, 119.1 and 29.84 ng/g lipid, respectively, and median
      concentrations of HCB and p,p'-DDE were 19.98 and 127.59 ng/g lipid,
      respectively. Age was positively correlated with serum levels of selected POPs.
      Women living in northern Tunisia showed higher serum levels of all PCBs. Working
      outside home and cereal consumption were positively associated to serum levels of
      p,p'-DDE. The duration of the lactation was also related to lower serum levels of
      p,p'-DDE and HCB. CONCLUSION: The levels of exposure to POPs found warrant a
      biomonitoring program in order to identify routes of exposure and population
      groups at higher risk. This program will help to establish prevention policies
      and to determine the association between exposure to POPs and chronic diseases.

PMID- 25585156
TI  - Monte Carlo simulations of the transformation and removal of Ag, TiO2, and ZnO
      nanoparticles in wastewater treatment and land application of biosolids.
AB  - The use of nano-enabled materials in industry and consumer products is increasing
      rapidly and with it, the more imperative it becomes to understand the
      consequences of such materials entering the environment during production, use or
      disposal. The novel properties of engineered nanomaterials (ENMs) that make them
      desirable for commercial applications also present the possibility of impacting
      aquatic and terrestrial environments in ways that may differ from materials in
      bulk format. Modeling techniques are needed to proactively predict the
      environmental fate and transport of nanomaterials. A model for nanoparticle (NP)
      separation and transformation in water treatment was parameterized for three
      metal and metal-oxide NPs. Functional assays to determine NP specific
      distribution and transformation were used to parameterize the model and obtain
      environmentally relevant concentrations of NPs and transformation byproducts
      leaving WWTPs in effluent and biosolids. All three NPs were predicted to
      associate >90% with the solid phase indicating significant accumulation in the
      biosolids. High rates of transformation for ZnO and Ag NPs resulted in ~97%
      transformation of the NPs that enter the plant despite differences in
      transformation rate in aerobic versus anaerobic environments. Due to high
      insolubility and negligible redox transformation, the only process predicted to
      impact TiO2 NP fate and transport in WWTPs was distribution between the solid and
      liquid phases. Subsequent investigation of ZnO NP species fate and transport when
      land applied in biosolids indicated that steady state concentrations of ZnO
      phases would likely be achieved after approximately 150days under loading
      conditions of biosolids typical in current practice. 

PMID- 25585157
TI  - Arsenic exposure to drinking water in the Mekong Delta.
AB  - Arsenic (As) contamination of groundwater drinking sources was investigated in
      the Mekong Delta, Vietnam in order to assess the occurrence of As in the
      groundwater, and the magnitude of As exposure of local residents through
      measurements of As in toenails of residents consuming groundwater as their major
      drinking water source. Groundwater (n=68) and toenail (n=62) samples were
      collected in Dong Thap Province, adjacent to the Mekong River, in southern
      Vietnam. Fifty-three percent (n=36) of the wells tested had As content above the
      World Health Organization's (WHO) recommended limit of 10 ppb. Samples were
      divided into Northern (mean As=4.0 ppb) and Southern (329.0 ppb) groups; wells
      from the Southern group were located closer to the Mekong River. Elevated As
      contents were associated with depth (<200 m), salinity (low salinity), and redox
      state (reducing conditions) of the study groundwater. In 79% of the wells, As was
      primarily composed of the reduced As(III) species. Arsenic content in nails
      collected from local residents was significantly correlated to As in drinking
      water (r=0.49, p<0.001), and the relationship improved for pairs in which As in
      drinking water was higher than 1 ppb (r=0.56, p<0.001). Survey data show that the
      ratio of As in nail to As in water varied among residents, reflecting
      differential As bioaccumulation in specific exposed sub-populations. The data
      show that water filtration and diet, particularly increased consumption of animal
      protein and dairy, and reduced consumption of seafood, were associated with lower
      ratios of As in nail to As in water and thus could play important roles in
      mitigating As exposure in areas where As-rich groundwater is the primary drinking
      water source.

PMID- 25585159
TI  - Solution transformation of Cu2O into CuInS2 for solar water splitting.
AB  - Though Cu2O has demonstrated high performance as a photocathode for solar water
      splitting, its band gap is too large for efficient use as the bottom cell in
      tandem configurations. Accordingly, copper chalcopyrites have recently attracted
      much attention for solar water splitting due to their smaller and tunable band
      gaps. However, their fabrication is mainly based on vacuum evaporation, which is
      an expensive and energy consuming process. Here, we have developed a novel and
      low-cost solution fabrication method, and CuInS2 was chosen as a model material
      due to its smaller band gap compared to Cu2O and relatively simple composition.
      The nanostructured CuInS2 electrodes were synthesized at low temperature in
      crystalline form by solvothermal treatment of electrochemically deposited Cu2O
      films. Following the coating of overlayers and decoration with Pt catalyst, the
      as-fabricated CuInS2 electrode demonstrated water splitting photocurrents of 3.5
      mA cm(-2) under simulated solar illumination. To the best of our knowledge, this
      is the highest performance yet reported for a solution-processed copper
      chalcopyrite electrode for solar water splitting. Furthermore, the electrode
      showed good stability and had a broad incident photon-to-current efficiency
      (IPCE) response to wavelengths beyond 800 nm, consistent with the smaller bandgap
      of this material. 

PMID- 25585158
TI  - Health impacts and economic losses assessment of the 2013 severe haze event in
      Beijing area.
AB  - Haze is a serious air pollution problem in China, especially in Beijing and
      surrounding areas, affecting visibility, public health and regional climate. In
      this study, the Weather Research and Forecasting-Chemistry (WRF-Chem) model was
      used to simulate PM2.5 (particulate matters with aerodynamic diameter<=2.5 MUm)
      concentrations during the 2013 severe haze event in Beijing, and health impacts
      and health-related economic losses were calculated based on model results.
      Compared with surface monitoring data, the model results reflected pollution
      concentrations accurately (correlation coefficients between simulated and
      measured PM2.5 were 0.7, 0.4, 0.5 and 0.6 in Beijing, Tianjin, Xianghe and
      Xinglong stations, respectively). Health impacts assessments show that the PM2.5
      concentrations in January might cause 690 (95% confidence interval (CI): (490,
      890)) premature deaths, 45,350 (95% CI: (21,640, 57,860)) acute bronchitis and
      23,720 (95% CI: (17,090, 29,710)) asthma cases in Beijing area. Results of the
      economic losses assessments suggest that the haze in January 2013 might lead to
      253.8 (95% CI: (170.2, 331.2)) million US$ losses, accounting for 0.08% (95% CI:
      (0.05%, 0.1%)) of the total 2013 annual gross domestic product (GDP) of Beijing.

PMID- 25585160
TI  - Highly stereocontrolled synthesis of trans-2,6-disubstituted-5-methyl-3,6
      dihydropyrans: stereoselective synthesis of the bicyclic core of penostatin B.
AB  - An efficient, mild, and highly diastereoselective strategy for the synthesis of
      trans-2,6-disubstituted-5-methyl-3,6-dihydropyran ring systems has been developed
      starting from delta-hydroxy alpha-methyl alpha,beta-unsaturated aldehydes and
      allyltrimethylsilane in the presence of a catalytic amount of ZnBr2 in a highly
      diastereoselective manner with excellent yield. The versatility of the above
      method was also demonstrated for the construction of the bicyclic core present in
      penostatin B in a concise and highly stereoselective manner. 

PMID- 25585161
TI  - RNA editing in plants: Machinery and flexibility of site recognition.
AB  - In plants, RNA editing is a process that deaminates specific cytidines (C) to
      uridines (U). PLS subfamily members of PPR proteins function in site recognition
      of the target C. In silico analysis has predicted the code used for PPR motif
      nucleotide interaction, and the crystal structure of a protein-RNA complex
      supports this model. Despite progress in understanding the RNA-binding mechanism
      of PPR proteins, some of the flexibility of RNA recognition observed in trans
      factors of RNA editing has not been fully explained. It is probably necessary to
      consider another unknown mechanism, and this consideration is related to the
      question of how PPR proteins have managed the creation of RNA editing sites
      during evolution. This question may be related to the mystery of the biological
      function of RNA editing in plants. MORF/RIP family members are required for RNA
      editing at multiple editing sites and are components of the RNA editosome in
      plants. The DYW domain has been a strong candidate for the C deaminase activity
      required for C-to-U conversion in RNA editing. So far, the activity of this
      enzyme has not been detected in recombinant DYW proteins, and several puzzling
      experimental results need to be explained to support the model. It is still
      difficult to resolve the entire image of the editosome in RNA editing in plants.
      This article is part of a Special Issue entitled: Chloroplast Biogenesis. 

PMID- 25585162
TI  - Stable nanoemulsions prepared via interfacial solidification of amphiphilic
      polyether-polyester block copolymers.
AB  - Oil-in-water (O/W) emulsions are generally stabilized by water-soluble
      surfactants, which anchor to the surface of oil droplets dispersed in an aqueous
      solution. Our recent work introduced a new approach to stabilize nanoemulsions
      through the formation of a semi-solid interphase at the O/W interface using a
      water-insoluble amphiphilic block copolymer, methoxy poly(ethylene glycol)-block
      poly(E-caprolactone). However, the approach is not applicable to relatively non
      polar oils due to the quick precipitation of the hydrophobic PCL block within the
      oil phase. Here we report on successful stabilization of non-polar liquid
      paraffin nanoemulsions using an amphiphilic copolymers having a new hydrophobic
      block comprising E-caprolactone and L-lactide. The new block copolymer was
      reorganized at the O/W interface of liquid paraffin, generating stable nano-sized
      emulsions via the formation of a robust semi-solid polymeric barrier. The
      prepared nanoemulsions show excellent dispersion stability even under a high
      level of mechanical stresses during freeze/thaw cycles. 

PMID- 25585163
TI  - Rapid automated microscopy for microbiological surveillance of ventilator
      associated pneumonia.
AB  - RATIONALE: Diagnosis of ventilator-associated pneumonia (VAP) is imprecise.
      OBJECTIVES: To (1) determine whether alternate-day surveillance mini
      bronchoalveolar lavage (mini-BAL) in ventilated adults could reduce time to
      initiation of targeted treatment and (2) evaluate the potential for automated
      microscopy to reduce analysis time. METHODS: Adult intensive care unit patients
      who were anticipated to require ventilation for at least a further 48 hours were
      included. Mini-BALs were processed for identification, quantitation, and
      antibiotic susceptibility, using (1) clinical culture (50 +/- 7 h) and (2)
      automated microscopy (~5 h plus offline analysis). MEASUREMENTS AND MAIN RESULTS:
      Seventy-seven mini-BALs were performed in 33 patients. One patient (3%) was
      clinically diagnosed with VAP. Of 73 paired samples, culture identified 7
      containing pneumonia panel bacteria (>10(4) colony-forming units/ml) from five
      patients (15%) (4 Staphylococcus aureus [3 methicillin-resistant S. aureus], 2
      Stenotrophomonas maltophilia, 1 Klebsiella pneumoniae) and resulted in
      antimicrobial changes/additions to two of five (40%) of those patients.
      Microscopy identified 7 of 7 microbiologically positive organisms and 64 of 66
      negative samples compared with culture. Antimicrobial responses were concordant
      in four of five comparisons. Antimicrobial changes/additions would have occurred
      in three of seven microscopy-positive patients (43%) had those results been
      clinically available in 5 hours, including one patient diagnosed later with VAP
      despite negative mini-BAL cultures. CONCLUSIONS: Microbiological surveillance
      detected infection in patients at risk for VAP independent of clinical signs,
      resulting in changes to antimicrobial therapy. Automated microscopy was 100%
      sensitive and 97% specific for high-risk pneumonia organisms compared with
      clinical culturing. Rapid microscopy-based surveillance may be informative for
      treatment and antimicrobial stewardship in patients at risk for VAP.

PMID- 25585164
TI  - Postprandial plasma betaine and other methyl donor-related responses after
      consumption of minimally processed wheat bran or wheat aleurone, or wheat
      aleurone incorporated into bread.
AB  - The bran and particularly the aleurone fraction of wheat are high in betaine and
      other physiological methyl donors, which may exert beneficial physiological
      effects. We conducted two randomised, controlled, cross-over postprandial studies
      to assess and compare plasma betaine and other methyl donor-related responses
      following the consumption of minimally processed bran and aleurone fractions
      (study A) and aleurone bread (study B). For both studies, standard
      pharmacokinetic parameters were derived for betaine, choline, folate,
      dimethylglycine (DMG), total homocysteine and methionine from plasma samples
      taken at 0, 0.5, 1, 2 and 3 h. In study A (n 14), plasma betaine concentrations
      were significantly and substantially elevated from 0.5 to 3 h following the
      consumption of both bran and aleurone compared with the control; however,
      aleurone gave significantly higher responses than bran. Small, but significant,
      increases were also observed in DMG measures; however, no significant responses
      were observed in other analytes. In study B (n 13), plasma betaine concentrations
      were significantly and substantially higher following consumption of the aleurone
      bread compared with the control bread; small, but significant, increases were
      also observed in DMG and folate measures in response to consumption of the
      aleurone bread; however, no significant responses were observed in other
      analytes. Peak plasma betaine concentrations, which were 1.7-1.8 times the
      baseline levels, were attained earlier following the consumption of minimally
      processed aleurone compared with the aleurone bread (time taken to reach peak
      concentration 1.2 v. 2.1 h). These results showed that the consumption of
      minimally processed wheat bran, and particularly the aleurone fraction, yielded
      substantial postprandial increases in plasma betaine concentrations. Furthermore,
      these effects appear to be maintained when aleurone was incorporated into bread. 

PMID- 25585165
TI  - Polypyrrole-supported membrane proteins for bio-inspired ion channels.
AB  - Biomedical platforms constructed by immobilizing membrane proteins in matrixes
      made of synthetic organic polymers is a challenge because the structure and
      function of these proteins are affected by environmental conditions. In this
      work, an operative composite that regulates the diffusion of alkali ions has been
      prepared by functionalizing a supporting matrix made of poly(N-methylpyrrole)
      (PNMPy) with a beta-barrel membrane protein (Omp2a) that forms channels and
      pores. The protein has been unequivocally identified in the composite, and its
      structure has been shown to remain unaltered. The PNMPy-Omp2a platform fulfills
      properties typically associated with functional bio-interfaces with biomedical
      applications (e.g., biocompatibility, biodegrabadility, and hydrophilicity). The
      functionality of the immobilized protein has been examined by studying the
      passive ion transport response in the presence of electrolytic solutions with
      Na(+) and K(+) concentrations close to those found in blood. Although the
      behavior of PNMPy and PNMPy-Omp2a is very similar for solutions with very low
      concentration, the resistance of the latter decreases drastically when the
      concentration of ions increases to ~100 mM. This reduction reflects an enhanced
      ion exchange between the biocomposite and the electrolytic medium, which is not
      observed in PNMPy, evidencing that PNMPy-Omp2a is particularly well suited to
      prepare bioinspired channels and smart biosensors. 

PMID- 25585168
TI  - In situ optical measurement of charge transport dynamics in organic
      photovoltaics.
AB  - We present a novel experimental approach which allows extraction of both spatial
      and temporal information on charge dynamics in organic solar cells. Using the
      wavelength dependence of the photonic structure in these devices, we monitor the
      change in spatial overlap between the photogenerated hole distribution and the
      optical probe profile as a function of time. In a model system we find evidence
      for a buildup of the photogenerated hole population close to the hole-extracting
      electrode on a nanosecond time scale and show that this can limit charge
      transport through space-charge effects under operating conditions. 

PMID- 25585166
TI  - Plasma lipidomics analysis finds long chain cholesteryl esters to be associated
      with Alzheimer's disease.
AB  - There is an urgent need for the identification of Alzheimer's disease (AD)
      biomarkers. Studies have now suggested the promising use of associations with
      blood metabolites as functional intermediate phenotypes in biomedical and
      pharmaceutical research. The aim of this study was to use lipidomics to identify
      a battery of plasma metabolite molecules that could predict AD patients from
      controls. We performed a comprehensive untargeted lipidomic analysis, using ultra
      performance liquid chromatography/mass spectrometry on plasma samples from 35 AD
      patients, 40 elderly controls and 48 individuals with mild cognitive impairment
      (MCI) and used multivariate analysis methods to identify metabolites associated
      with AD status. A combination of 10 metabolites could discriminate AD patients
      from controls with 79.2% accuracy (81.8% sensitivity, 76.9% specificity and an
      area under curve of 0.792) in a novel test set. Six of the metabolites were
      identified as long chain cholesteryl esters (ChEs) and were reduced in AD (ChE
      32:0, odds ratio (OR)=0.237, 95% confidence interval (CI)=0.10-0.48, P=4.19E-04;
      ChE 34:0, OR=0.152, 95% CI=0.05-0.37, P=2.90E-04; ChE 34:6, OR=0.126, 95% CI=0.03
      0.35, P=5.40E-04; ChE 32:4, OR=0.056, 95% CI=0.01-0.24, P=6.56E-04 and ChE 33:6,
      OR=0.205, 95% CI=0.06-0.50, P=2.21E-03, per (log2) metabolite unit). The levels
      of these metabolites followed the trend control>MCI>AD. We, additionally, found
      no association between cholesterol, the precursor of ChE and AD. This study
      identified new ChE molecules, involved in cholesterol metabolism, implicated in
      AD, which may help identify new therapeutic targets; although, these findings
      need to be replicated in larger well-phenotyped cohorts. 

PMID- 25585169
TI  - Amorphous host materials based on Troger's base scaffold for application in
      phosphorescent organic light-emitting diodes.
AB  - Troger's bases (TBs) functionalized with carbazoles (TB-Czs) and phosphine oxides
      (TB-POs) were designed and synthesized as host materials for application in
      phosphorescent organic light-emitting diodes. The TB scaffold is shown to impart
      thermal stability with high Tg values (171-211  degrees C) as well as high
      triplet energies in the range of 2.9-3.0 eV. With a limited experimentation of
      the devices, it is shown that the TBs doped with a green phosphor, namely,
      Ir(ppy)3, permit impressive external efficiencies on the order of ca. 16% with a
      high brightness of ca. 3000-4000 cd/m2. Better device performance results are
      demonstrated by a small structural manipulation of the TB scaffold involving
      substitution of methyl groups in the core scaffold.

PMID- 25585170
TI  - A spontaneous single-crystal-to-single-crystal polymorphic transition involving
      major packing changes.
AB  - 4,6-O-Benzylidene-alpha-d-galactosyl azide crystallizes into two morphologically
      distinct polymorphs depending on the solvent. While the alpha form appeared as
      thick rods and crystallized in P21 space group (monoclinic) with a single
      molecule in the asymmetric unit, the beta form appeared as thin fibers and
      crystallized in P1 space group (triclinic) with six molecules in the asymmetric
      unit. Both the polymorphs appeared to melt at the same temperature. Differential
      scanning calorimetry analysis revealed that polymorph alpha irreversibly
      undergoes endothermic transition to polymorph beta much before its melting point,
      which accounts for their apparently same melting points. Variable temperature
      powder X-ray diffraction (PXRD) experiments provided additional proof for the
      polymorphic transition. Single-crystal XRD analyses revealed that alpha to beta
      transition occurs in a single-crystal-to-single-crystal (SCSC) fashion not only
      under thermal activation but also spontaneously at room temperature. The SCSC
      nature of this transition is surprising in light of the large structural
      differences between these polymorphs. Polarized light microscopy experiments not
      only proved the SCSC nature of the transition but also suggested nucleation and
      growth mechanism for the transition. 

PMID- 25585167
TI  - Predictors of treatment response in young people at ultra-high risk for psychosis
      who received long-chain omega-3 fatty acids.
AB  - Previous efforts in the prospective evaluation of individuals who experience
      attenuated psychotic symptoms have attempted to isolate mechanisms underlying the
      onset of full-threshold psychotic illness. In contrast, there has been little
      research investigating specific predictors of positive outcomes. In this study,
      we sought to determine biological and clinical factors associated with treatment
      response, here indexed by functional improvement in a pre-post examination of a
      12-week randomized controlled intervention in individuals at ultra-high risk
      (UHR) for psychosis. Participants received either long-chain omega-3 (omega-3)
      polyunsaturated fatty acids (PUFAs) or placebo. To allow the determination of
      factors specifically relevant to each intervention, and to be able to contrast
      them, both treatment groups were investigated in parallel. Univariate linear
      regression analysis indicated that higher levels of erythrocyte membrane alpha
      linolenic acid (ALA; the parent fatty acid of the omega-3 family) and more severe
      negative symptoms at baseline predicted subsequent functional improvement in the
      treatment group, whereas less severe positive symptoms and lower functioning at
      baseline were predictive in the placebo group. A multivariate machine learning
      analysis, known as Gaussian Process Classification (GPC), confirmed that baseline
      fatty acids predicted response to treatment in the omega-3 PUFA group with high
      levels of sensitivity, specificity and accuracy. In addition, GPC revealed that
      baseline fatty acids were predictive in the placebo group. In conclusion, our
      investigation indicates that UHR patients with higher levels of ALA may
      specifically benefit from omega-3 PUFA supplementation. In addition, multivariate
      machine learning analysis suggests that fatty acids could potentially be used to
      inform prognostic evaluations and treatment decisions at the level of the
      individual. Notably, multiple statistical analyses were conducted in a relatively
      small sample, limiting the conclusions that can be drawn from what we believe to
      be a first-of-its-kind study. Additional studies with larger samples are
      therefore needed to evaluate the generalizability of these findings. 

PMID- 25585172
TI  - Profiling lymphocyte interactions at the single-cell level by microfluidic cell
      pairing.
AB  - Establishing a successful immune response requires cell-cell interactions, where
      the nature of antigen presentation dictates functional outcomes. Methods to study
      these interactions, however, suffer from limited throughput and a lack of control
      over cell pairing. Here we describe a microfluidic platform that achieves high
      throughput deterministic pairing of lymphocytes with a defined contact time,
      thereby allowing accurate assessment of early activation events for each pair in
      controlled microenvironments. More importantly, the platform allows the capture
      of dynamic processes and static parameters from both partners simultaneously,
      thus enabling pairwise-correlated multiparametric profiling of lymphocyte
      interactions over hundreds of pairs in a single experiment. Using our platform,
      we characterized early activation dynamics of CD8 T cells (OT-1 and TRP1
      transnuclear (TN)) and investigated the extent of heterogeneity in T-cell
      activation and the correlation of multiple readouts. The results establish our
      platform as a promising tool for quantitative investigation of lymphocyte
      interactions. 

PMID- 25585171
TI  - Synthetic scrapie infectivity: interaction between recombinant PrP and scrapie
      brain-derived RNA.
AB  - The key molecular event in human cerebral proteinopathies, which include
      Alzheimer's, Parkinson's and Huntington's diseases, is the structural conversion
      of a specific host protein into a beta-sheet-rich conformer. With regards to this
      common mechanism, it appears difficult to explain the outstanding infectious
      properties attributed to PrP(Sc), the hallmark of another intriguing family of
      cerebral proteinopathies known as transmissible spongiform encephalopathies (TSE)
      or prion diseases. The infectious PrP(Sc) or "prion" is thought to be composed
      solely of a misfolded form of the otherwise harmless cellular prion protein
      (PrP(c)). To gain insight into this unique situation, we used the 263K scrapie
      hamster model to search for a putative PrP(Sc)-associated factor that contributes
      to the infectivity of PrP(Sc) amyloid. In a rigorously controlled set of
      experiments that included several bioassays, we showed that originally innocuous
      recombinant prion protein (recPrP) equivalent to PrP(c) is capable of initiating
      prion disease in hamsters when it is converted to a prion-like conformation (beta
      sheet-rich) in the presence of RNA purified from scrapie-associated fibril (SAF)
      preparations. Analysis of the recPrP-RNA infectious mixture reveals the presence
      of 2 populations of small RNAs of approximately 27 and 55 nucleotides. These
      unprecedented findings are discussed in light of the distinct relationship that
      may exist between this RNA material and the 2 biological properties, infectivity
      and strain features, attributed to prion amyloid. 

PMID- 25585175
TI  - Publishing consultant outcomes data: room for improvement.

PMID- 25585174
TI  - First evidence that oligopyridines, alpha-helix foldamers, inhibit Mcl-1 and
      sensitize ovarian carcinoma cells to Bcl-xL-targeting strategies.
AB  - Apoptosis control defects such as the deregulation of Bcl-2 family member
      expression are frequently involved in chemoresistance. In ovarian carcinoma, we
      previously demonstrated that Bcl-xL and Mcl-1 cooperate to protect cancer cells
      against apoptosis and their concomitant inhibition leads to massive apoptosis
      even in the absence of chemotherapy. Whereas Bcl-xL inhibitors are now available,
      Mcl-1 inhibition, required to sensitize cells to Bcl-xL-targeting strategies,
      remains problematic. In this context, we designed and synthesized oligopyridines
      potentially targeting the Mcl-1 hydrophobic pocket, evaluated their capacity to
      inhibit Mcl-1 in live cells, and implemented a functional screening assay to
      evaluate their ability to sensitize ovarian carcinoma cells to Bcl-xL-targeting
      strategies. We established structure-activity relationships and focused our
      attention on MR29072, named Pyridoclax. Surface plasmon resonance assay
      demonstrated that pyridoclax directly binds to Mcl-1. Without cytotoxic activity
      when administered as a single agent, pyridoclax induced apoptosis in combination
      with Bcl-xL-targeting siRNA or with ABT-737 in ovarian, lung, and mesothelioma
      cancer cells. 

PMID- 25585176
TI  - Electronic referrals from hospital bedsides to community pharmacies.

PMID- 25585173
TI  - Targeted release of tobramycin from a pH-responsive grafted bilayer challenged
      with S. aureus.
AB  - A stimuli-responsive, controlled release bilayer for the prevention of bacterial
      infection on biomaterials is presented. Drug release is locally controlled by the
      pH-responsiveness of the bilayer, comprised of an inner poly(acrylic acid) (PAA)
      monolayer grafted to a biomaterial and cross-linked with an outer chitosan (CH)
      brush. Tobramycin (TOB) is loaded in the inner PAA in part to minimize bacteria
      resistance. Because biofilm formation causes a decrease in local pH, TOB is
      released from PAA and permeates through the CH, which is in contact with the
      biofilm. Antibiotic capacity is controlled by the PAA thickness, which depends on
      PAA brush length and the extent of cross-linking between CH and PAA at the
      bilayer interface. This TOB-loaded, pH-responsive bilayer exhibits significantly
      enhanced antibacterial activity relative to controls. 

PMID- 25585178
TI  - Periprosthetic joint infection in total hip arthroplasty: prevention and
      management.
AB  - Periprosthetic joint infection is a devastating complication. Orthopaedic
      surgeons must prevent, anticipate, rapidly diagnose and effectively manage such
      patients in the multidisciplinary setting. This review discusses current
      strategies in the management of these patients following total hip arthroplasty. 

PMID- 25585179
TI  - Panton-Valentine leukocidin osteomyelitis in children: a growing threat.
AB  - Panton-Valentine leukocidin-producing Staphylococcus aureus osteomyelitis is
      associated with multiple complications including multiple abscesses, deep vein
      thrombosis and fulminant sepsis. This article reviews the literature concerning
      this emerging threat which is currently under-recognized. 

PMID- 25585180
TI  - Paget's disease: a clinical review.
AB  - Paget's disease was first described more than 150 years ago, but the exact cause
      is still unknown--genes and the environment are both important. This article
      explores the basic science and clinical aspects of this intriguing condition.

PMID- 25585181
TI  - Treat to target in managing inflammatory arthritis.
AB  - Treating to target has been used in many areas of medicine, including diabetes
      mellitus and cardiovascular disease risk. This principle has now been applied to
      rheumatological conditions, notably inflammatory arthritis. This article
      discusses the role and importance of this management approach in inflammatory
      arthritis. 

PMID- 25585182
TI  - Treatment of diabetic maculopathy.
AB  - Diabetic maculopathy is an important cause of severe sight impairment. There has
      been a significant evolution in its treatment over the past decade and laser
      treatment is now largely being superseded by intravitreal injections of anti
      vascular endothelial growth factor agents or corticosteroids. 

PMID- 25585183
TI  - Promoting high value inpatient care via a coaching model of structured,
      interdisciplinary team rounds.
AB  - The professional development of early career hospital physicians may be improved
      by embedding an experienced physician in a coaching role during structured,
      interdisciplinary team rounds. This article gives a descriptive report of such a
      model and discusses how it may promote delivery of high-value care to adult
      inpatients. 

PMID- 25585184
TI  - Improving communication with primary care to ensure patient safety post-hospital
      discharge.
AB  - INTRODUCTION: Successful communication between hospitals and primary care is of
      paramount importance to enable continuity of care and maintain patient safety
      post-discharge. Discharge summaries are the simplest way for GPs to obtain
      information about a patient's hospital stay. A quality improvement study was
      conducted with the aim of increasing the content of discharge summaries for
      inpatients in the authors' department. METHODS: A prospective review of 60
      electronic discharge summaries was conducted over a 6-week period. The content of
      discharge summaries was reviewed in accordance with local trust guidelines.
      Targeted, intensive, cost and time-effective educational interventions were then
      conducted. A post-intervention review of 60 discharge summaries was performed. A
      further review of 60 discharge summaries was performed after 12 months. RESULTS:
      Initial results pre-intervention confirmed suboptimal content of discharge
      summaries. Post-intervention results showed each component of discharge summaries
      improved in terms of content, with six of eight components having a statistically
      significant (P<0.05) increase. This was maintained after 12 months. CONCLUSIONS:
      This study has demonstrated how simple, intensive educational sessions can lead
      to an improvement in discharge summaries and communication with primary care.

PMID- 25585185
TI  - A case of a prolapsed facial nerve into the middle ear cavity.

PMID- 25585186
TI  - Extreme photosensitivity in a patient with erythropoietic protoporphyria.

PMID- 25585187
TI  - A stroke of ill-fortune: an unexpected diagnosis following a stroke-like event.

PMID- 25585188
TI  - Littoral cell angioma in the spleen.

PMID- 25585189
TI  - Horace Wells: pioneer of nitrous oxide anaesthesia.

PMID- 25585191
TI  - End-of-life care in patients with chronic obstructive pulmonary disease.

PMID- 25585192
TI  - Borderline personality disorder.

PMID- 25585193
TI  - Cell culture.

PMID- 25585194
TI  - Dying for a change: junior doctors and care of the dying patient.

PMID- 25585195
TI  - Commentary: Sexual health and human rights in the Middle East and North Africa:
      progress or backlash?

PMID- 25585196
TI  - Volatiles from nineteen recently genome sequenced actinomycetes.
AB  - The volatiles released by agar plate cultures of nineteen actinomycetes whose
      genomes were recently sequenced were collected by use of a closed-loop stripping
      apparatus (CLSA) and analysed by GC/MS. In total, 178 compounds from various
      classes were identified. The most interesting findings were the detection of the
      insect pheromone frontalin in Streptomyces varsoviensis, and the emission of the
      unusual plant metabolite 1-nitro-2-phenylethane. Its biosynthesis from
      phenylalanine was investigated in isotopic labelling experiments. Furthermore,
      the identified terpenes were correlated to the information about terpene cyclase
      homologs encoded in the investigated strains. The analytical data were in line
      with functionally characterised bacterial terpene cyclases and particularly
      corroborated the recently suggested function of a terpene cyclase from
      Streptomyces violaceusniger by the identification of a functional homolog in
      Streptomyces rapamycinicus. 

PMID- 25585197
TI  - The effects of glucuronic acid and N-acetyl-D-glucosamine on in vitro
      fertilisation of porcine oocytes.
AB  - High incidences of polyspermic penetration continue to challenge researchers
      during porcine in vitro fertilisation (IVF). The aim of this study was to reduce
      the incidence of polyspermy by increasing the perivitelline space thickness with
      glucuronic acid and N-acetyl-D-glucosamine (GlcNAc) supplementation during oocyte
      maturation. After maturation, zona pellucida and perivitelline space thicknesses,
      intracellular glutathione concentrations and fertilisation kinetics were
      measured, in addition to embryonic cleavage and blastocyst formation at 48h and
      144h after IVF, respectively. There were no significant differences between the
      treatments for zona pellucida thickness, penetration rates, male pronuclear
      formation or cortical granule exocytosis. Glucuronic acid supplementation
      significantly increased (PPPP<0.05) of cleavage and blastocyst formation by 48
      and 144h after IVF compared with all other groups. These results indicate that
      supplementing with 0.005mM glucuronic acid and 0.005mM GlcNAc during oocyte
      maturation decreases the incidence of polyspermic penetration by increasing
      perivitelline space thickness and improving embryo development in pigs.

PMID- 25585198
TI  - Implementing an intimate partner violence (IPV) screening protocol in HIV care.
AB  - HIV and intimate partner violence (IPV) epidemics propagate and interact in a
      syndemic fashion contributing to excess burden of disease and poorer health
      outcomes. In order to understand the impact of IPV on HIV disease management, a
      universal screening program was implemented in the Southern Alberta Clinic in May
      2009. We evaluated our IPV screening protocol and made recommendations for its
      usage in HIV care. IPV data obtained from patients were evaluated, supplemented
      with responses from a subset of in-depth interviews. 35% of 1721 patients
      reported experiencing IPV. Prevalence was higher among females (46%), Aboriginal
      Canadians (67%), bisexual male/females (48%), and gay males (35%). Of 158
      patients interviewed, only 22% had previously been asked about IPV in any health
      care setting. Patients were responsive to routine IPV screening emphasizing that
      referral services need to be easily accessible. 23% of patients disclosing IPV
      subsequently connected to additional IPV resources after screening. We recommend
      that universal IPV screening be incorporated within regular HIV clinic care. The
      IPV survey should be given after trust has been established with regular follow
      up every 6-12 months. A referral process to local agencies dealing with IPV must
      be in place for patients disclosing abuses. 

PMID- 25585199
TI  - Graphene and graphitic derivative filled polymer composites as potential sensors.
AB  - Graphite and numerous graphitic-derived micro- and nano-particles have gained
      importance in current materials science research. These two-dimensional sheets of
      sp(2)-hybridized carbon atoms remarkably influence the properties of polymers.
      Graphene mono-layers, graphene oxides, graphite oxides, exfoliated graphite, and
      other related materials are derived from a parental graphite structure. In this
      review, we focus primarily on the role of these fillers in regulating the
      electrical and sensing properties of polymer composites. It has been demonstrated
      that the addition of an optimized mixture of graphene and or its derivatives to
      various polymers produces a record-high enhancement of the electrical
      conductivity and achieved semiconducting characteristics at small filler loading,
      making it suitable for sensor manufacture. Promising sensing characteristics are
      observed in graphite-derived composite films compared with those of micro-sized
      composites and the properties are explained mainly based on the filler volume
      fraction, nature and rate of dispersion and the filler polymer interactions at
      the interface. In short, this critical review aims to provide a thorough
      understanding of the recent advances in the area of graphitic-based polymer
      composites in advanced electronics. Future perspectives in this rapidly
      developing field are also discussed. 

PMID- 25585200
TI  - Selected dietary (poly)phenols inhibit periodontal pathogen growth and biofilm
      formation.
AB  - Periodontitis (PD) is a chronic infectious disease mediated by bacteria in the
      oral cavity. (Poly)phenols (PPs), ubiquitous in plant foods, possess
      antimicrobial activities and may be useful in the prevention and management of
      periodontitis. The objective of this study was to test the antibacterial effects
      of selected PPs on periodontal pathogens, on both planktonic and biofilm modes of
      growth. Selected PPs (n = 48) were screened against Streptococcus mitis (S.
      mitis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans),
      Fusobacterium nucleatum (F. nucleatum) and Porphyromonas gingivalis (P.
      gingivalis). The antibacterial potential of each compound was evaluated in terms
      of planktonic minimum inhibitory concentration (PMIC) and planktonic minimum
      bactericidal concentration (PMBC) using standardized broth microdilution assays.
      The most active PPs were further tested for their effect on mono-species and
      multi-species biofilms using a colorimetric resazurin-based viability assay and
      scanning electron microscopy. Of the 48 PPs tested, 43 showed effective
      inhibition of planktonic growth of one or more test strains, of which curcumin
      was the most potent (PMIC range = 7.8-62.5 MUg mL(-1)), followed by pyrogallol
      (PMIC range = 2.4-2500 MUg mL(-1)), pyrocatechol (MIC range = 4.9-312.5 MUg mL(
      1)) and quercetin (PMIC range = 31.2-500 MUg mL(-1)). At this concentration,
      adhesion of curcumin and quercetin to the substrate also inhibited adhesion of S.
      mitis, and biofilm formation and maturation. While both curcumin and quercetin
      were able to alter architecture of mature multi-species biofilms, only curcumin
      treated biofilms displayed a significantly reduced metabolic activity. Overall,
      PPs possess antibacterial activities against periodontopathic bacteria in both
      planktonic and biofilm modes of growth. Further cellular and in vivo studies are
      necessary to confirm their beneficial activities and potential use in the
      prevention and or treatment of periodontal diseases. 

PMID- 25585201
TI  - A Novel Preclinical Model of Moderate Primary Blast-Induced Traumatic Brain
      Injury.
AB  - Blast-induced traumatic brain injury (bTBI) is the "signature" injury of the
      recent Iraq and Afghanistan wars. Here, we present a novel method to induce bTBI
      using shock wave (SW) lithotripsy. Using a lithotripsy machine, Wistar rats (N =
      70; 408.3 +/- 93 g) received five SW pulses to the right side of the frontal
      cortex at 24 kV and a frequency of 60 Hz. Animals were then randomly divided into
      three study endpoints: 24 h (n = 25), 72 h (n = 19) and 168 h (n = 26).
      Neurological and behavioral assessments (Garcia's test, beam walking, Rotarod,
      and elevated plus maze) were performed at the baseline, and further assessments
      followed at 3, 6, 24, 72, and 168 h post-injury, if applicable. We performed
      digital subtraction angiography (DSA) to assess presence of cerebral vasospasm
      due to induced bTBI. Damage to brain tissue was assessed by an overall
      histological severity (OHS) score based on depth of injury, area of hemorrhage,
      and extent of axonal injury. Except for beam walking, OHS was significantly
      correlated with the other three outcome measures with at least one of their
      assessments during the first 6 h after the experiment. OHS manifested the highest
      absolute correlation coefficients with anxiety at the baseline and 6 h post
      injury (r(baseline) = -0.75, r(6hrs) = 0.85; p<0.05). Median hemispheric
      differences for contrast peak values (obtained from DSA studies) for 24, 72, and
      168 h endpoints were 3.45%, 3.05% and 0.2%, respectively, with statistically
      significant differences at 1 versus 7 d (p<0.05) and 3 versus 7 d (p<0.01). In
      this study, we successfully established a preclinical rat model of bTBI with
      characteristics similar to those observed in clinical cases. This new method may
      be useful for future investigations aimed at understanding bTBI pathophysiology.

PMID- 25585202
TI  - Characteristics of benign and malignant thyroid disease in familial adenomatous
      polyposis patients and recommendations for disease surveillance.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) is a hereditary colon cancer
      syndrome that involves multiple extracolonic organs, including the thyroid.
      Several studies have estimated the rate of thyroid cancer in FAP to occur at five
      times the rate of the general population, but no current consensus defines
      screening for thyroid cancer in this cohort. This study seeks to define the
      features of benign and malignant thyroid disease in FAP patients, to compare
      thyroid cancer cases found through screening with those found incidentally, and
      to propose disease surveillance recommendations. METHODS: Prospective screening
      for early thyroid cancer detection with thyroid ultrasound (US) was performed on
      FAP patients at the time of annual colonoscopy since November 2008. Clinical and
      US data were reviewed to characterize the observed thyroid nodules. Nonscreening
      detected cases (NSD) were found through review of the colon cancer registry
      database. RESULTS: Eighteen NSD were found, compared with 15 screening-detected
      (SD) cases, out of 205 total patients screened (Mage=42 years; 55% female). The
      mean tumor size was larger in the NSD group than the SD group (p=0.04), and they
      tended to demonstrate more positive lymph nodes and more complications than the
      SD group. In the screened cohort, at least one thyroid nodule was detected in 106
      (51.7%) patients, with 90% of these seen on initial exam. A total of 40/106
      (37.7%) patients required fine-needle aspiration biopsy of a dominant nodule
      (Msize=14 mm), and 28/40 (70%) of these were performed at the first US visit.
      Suspicious US features were present in 16/40 (40%) patients, including five sub
      centimeter nodules. Cytology and/or nodule US was abnormal in 15/205 screened
      patients, leading to surgery and revealing 14 papillary and one medullary thyroid
      cancer. CONCLUSIONS: Given the age and sex distribution of the screened cohort,
      this study reveals a higher-than-expected prevalence of both benign and malignant
      thyroid disease in the FAP population. Additionally, SD cases seemed to consist
      of smaller-sized cancers that required less radical therapy compared to NSD
      cases. Since it was found that the initial US in the screening program accounted
      for the majority of detected nodules (90%) and biopsies (70%), baseline and
      subsequent thyroid US surveillance is recommended in all FAP patients.

PMID- 25585203
TI  - Governmental re-evaluation of the committed effective dose received by emergency
      workers at the TEPCO Fukushima Daiichi NPP accident.
AB  - In April 2013, the Ministry of Health, Labour and Welfare (MHLW) noticed that
      significant discrepancies were present between the committed effective dose (CED)
      data for emergency workers at the TEPCO Fukushima Daiichi Nuclear Power Plant
      provided by TEPCO and that reported by five primary contractors. The MHLW, based
      on re-evaluation of the data, provided administrative guidance which required
      TEPCO and the five primary contractors to readjust the CED data for 479 workers
      (2.5% of 19,346 emergency workers). Of these, data for 450 workers from the
      primary contractors were readjusted based on the change in assessment methods.
      Doses were readjusted to higher values for 431 workers and doses were readjusted
      to lower values for 19 workers, CED data were corrected due to calculation errors
      for 29 workers from seven contractors, 12 additional workers were found to have
      received more than 50 mSv but no more than 100 mSv, an increase of 1.7% over the
      previously established count of 723 workers who had received that dose. Six
      additional workers were found to have received more than 100 mSv, an increase of
      3.6% compared with the previous count of 167 workers. Major issues addressed
      during re-evaluation included: a) selection of intake scenario for the
      calculation of the residual activity ratio; b) assumptions about the intake date;
      c) assessments of exposure to radiation from (132)I and (132)Te; and d)
      assumptions about (131)I exposure in cases where (131)I was undetectable.
      Regarding the divergent CED data of 138 workers, the MHLW also confirmed that the
      CEDs assessed by the primary contractors were valid. To prevent the recurrence of
      similar incidents, the MHLW issued administrative guidance documents to TEPCO and
      primary contractors to employ standardized CED assessment methods on July 5.
      2013. 

PMID- 25585204
TI  - Synthesis of nanoporous 1,2,4-oxadiazole networks with high CO2 capture capacity.
AB  - Developing an adsorbent to mitigate carbon dioxide without large energy penalty
      is highly desired. Here, we present a silylation synthetic route to form a
      processable and otherwise impossible porous 1,2,4-oxadiazole network, which
      achieves 2 mmol g(-1) of CO2 capacity owing to a nitrogen-rich structure. This
      network shows high CO2-N2 selectivity, thermal stability up to 450  degrees C,
      and low heat of adsorption (26.4 kJ mol(-1)), facilitating easy regeneration. 

PMID- 25585205
TI  - Going global: the functions of autobiographical memory in cultural context.
AB  - This special issue of Memory brings together research from around the globe, from
      Japanese, Chinese and East Indian cultures, to American and European societies,
      to the Caribbean, to Turkey and to Australia and New Zealand, which examines how
      and why people, from childhood to old age, remember the personal past in daily
      life. This journey highlights the important role of the cultural context in
      shaping the functional usages of autobiographical memory. We illuminate six major
      contributions of cross-cultural research to a broader and deeper understanding of
      the functions of autobiographical memory, and call attention to the filed that
      memory research must "go global." 

PMID- 25585206
TI  - Going global: functions of autobiographical remembering world tour.
AB  - This special issue showcases research from around the world that takes a
      functional approach to autobiographical remembering. In doing so, it inspires
      researchers to reach out to new populations. This commentary begins with a brief
      history of the functional approach. Person-environment interactions, in this case
      how individuals use memory in their current cultural context, are at the core of
      that approach. Based on current theoretical thinking in this area, I review the
      papers in this issue with the aim of exploring: (1) where culture and function
      might fit in current conceptualisations of autobiographical memory, (2) the
      relation of culture to socio-structural variables such as gender and life phase
      in shaping the functions of memory and (3) differences in cultural tendencies to
      use autobiographical memory as a resource to fulfil universal human needs. 

PMID- 25585208
TI  - High-areal-capacity lithium storage of the Kirkendall effect-driven hollow
      hierarchical NiS(x) nanoarchitecture.
AB  - Three-dimensional (3-D) architectures can provide significant advantages as
      lithium ion microbattery electrodes by lengthening the vertical dimension. In
      addition, the nanoscale hierarchy and hollow properties are important factors for
      enhancing the performance. Here, we prepared a 3-D nickel sulfide
      nanoarchitecture via a facile low-temperature solution route. A Kirkendall effect
      driven sulfidation of a 3-D nickel electrode was used to produce a hollow 3-D
      structure. Moreover, a nanoscale hierarchy can be formed with the use of highly
      concentrated sulfur species. The morphology, structure, and chemical composition
      of the 3-D nickel sulfide electrode are characterized in detail, and the
      formation mechanism is discussed based on a time-resolved study. The 3-D nickel
      sulfide electrodes show an outstanding areal capacity (1.5 mA h cm(-2) at a
      current rate of 0.5 mA cm(-2)), making this electrode a potential electrode for 3
      D lithium ion microbatteries with a large energy density. Moreover, this strategy
      is expected to provide a general fabrication method for transition metal sulfide
      nanoarchitectures. 

PMID- 25585209
TI  - KAP1 is a Novel Substrate for the Arginine Methyltransferase PRMT5.
AB  - KRAB-associated protein 1 (KAP1), the transcriptional corepressor of Kruppel
      associated box zinc finger proteins (KRAB-ZFPs), is subjected to multiple post
      translational modifications that are involved in fine-tuning of the multiple
      biological functions of KAP1. In previous papers, we analyzed the KAP1-dependent
      molecular mechanism of transcriptional repression mediated by ZNF224, a member of
      the KRAB-ZFP family, and identified the protein arginine methyltransferase PRMT5
      as a component of the ZNF224 repression complex. We demonstrated that PRMT5
      mediated histone arginine methylation is required to elicit ZNF224
      transcriptional repression. In this study, we show that KAP1 interacts with PRMT5
      and is a novel substrate for PRMT5 methylation. Also, we present evidence that
      the methylation of KAP1 arginine residues regulate the KAP1-ZNF224 interaction,
      thus suggesting that this KAP1 post-translational modification could actively
      contribute to the regulation of ZNF224-mediated repression. 

PMID- 25585210
TI  - Segmentation-based attenuation correction in positron emission
      tomography/magnetic resonance: erroneous tissue identification and its impact on
      positron emission tomography interpretation.
AB  - OBJECTIVES: The objective of this study was to evaluate the frequency and
      characteristics of artifacts in segmentation-based attenuation correction maps
      (MU-maps) of positron emission tomography/magnetic resonance (PET/MR) and their
      impact on PET interpretation and the standardized uptake value (SUV)
      quantification in normal tissue and lesions. MATERIALS AND METHODS: The study was
      approved by the local institutional review board. Attenuation maps of 100
      patients with PET/MR and preceding PET/computed tomography examination were
      retrospectively inspected for artifacts (tracers: 2-deoxy-2-[18F]fluoro-D-glucose
      (18F-FDG), 11C-Choline, 68Ga-DOTATOC, 68Ga-DOTATATE, 11C-Methionine). The
      artifacts were subdivided into 9 different groups on the basis of their
      localization and appearance. The impact of MU-map artifacts in normal tissue and
      lesions on PET interpretation was evaluated qualitatively via visual analysis in
      synopsis with the non-attenuation-corrected (NAC) PET as well as quantitatively
      by comparing the SUV in artifact regions to reference regions. RESULTS:
      Attenuation map artifacts were found in 72% of the head/neck data sets, 61% of
      the thoracic data sets, 25% of the upper abdominal data sets, and 26% of the
      pelvic data sets. The most frequent localizations of the overall 276 artifacts
      were around metal implants (16%), in the lungs (19%), and outer body contours
      (31%). Twenty-one percent of all PET-avid lesions (38 of 184 lesions) were
      affected by artifacts in the majority without further consequences for visual PET
      interpretation. However, 9 PET-avid lung lesions were masked owing to MU-map
      artifacts and, thus, were only detectable on the NAC PET or additional MR imaging
      sequences. Quantitatively, MU-map artifacts led to significant SUV changes in
      areas with erroneous assignment of air instead of soft tissue (ie, metal
      artifacts) and of soft tissue instead of lung. Nevertheless, no change in
      diagnosis would have been caused by MU-map artifacts. CONCLUSIONS: Attenuation
      map artifacts that occur in a considerable percentage of PET/MR data sets have
      the potential to falsify PET quantification and visual PET interpretation.
      Nevertheless, on the basis of the present data, in the clinical interpretation
      setup, no changes in diagnosis due to MU-map artifacts may occur, especially when
      the MU-maps are checked for artifacts and PET/MR is read in synopsis with the NAC
      PET, if artifacts are present.

PMID- 25585211
TI  - Drop this archaic practice.

PMID- 25585214
TI  - "No education about me without me": a shared decision-making approach to patient
      education.

PMID- 25585215
TI  - Improving the inpatient influenza vaccination process.

PMID- 25585216
TI  - Caught somewhere in between: a journey from cancer patient to nursing student.

PMID- 25585217
TI  - We save lives: an informatics perspective on innovation.

PMID- 25585218
TI  - Achieving success when returning to nursing education.

PMID- 25585223
TI  - Waist loss and the irrelevant scale.

PMID- 25585219
TI  - Hourly rounding and patient falls: what factors boost success?
AB  - BACKGROUND: Falls are a persistent problem in all healthcare settings, with rates
      in acute care hospitals ranging from 1.3 to 8.9 falls per 1,000 inpatient days,
      about 30% resulting in serious injury. METHODS: A 30-day prospective pilot study
      was conducted on two units with pre- and postimplementation evaluation to
      determine the impact of patient-centered proactive hourly rounding on patient
      falls as part of a Lean Six Sigma process improvement project. Nurse leaders and
      a staff champion from Unit 1 were involved in the process from the start of the
      implementation period, while Unit 2 was introduced to the project for training
      shortly before the intervention began. RESULTS: On Unit 1, where staff and
      leadership were engaged in the project from the outset, the 1-year baseline mean
      fall rate was 3.9 falls/1,000 patient days. The pilot period fall rate of 1.3
      falls/1,000 patient days was significantly lower than the baseline fall rate (P =
      0.006). On Unit 2, where there was no run-in period, the 1-year baseline mean
      fall rate was 2.6 falls/1,000 patient days, which fell, but not significantly, to
      2.5 falls/1,000 patient days during the pilot period (P = 0.799). DISCUSSION:
      Engaging an interdisciplinary team, including leadership and unit champions, to
      complete a Lean Six Sigma process improvement project and implement a patient
      centered proactive hourly rounding program was associated with a significant
      reduction in the fall rate in Unit 1. Implementation of the same program in Unit
      2 without engaging leadership or front-line staff in program design did not
      impact its fall rate. CONCLUSIONS: The active involvement of leadership and front
      line staff in program design and as unit champions during the project run-in
      period was critical to significantly reducing inpatient fall rates and call bell
      use in an adult medical unit.

PMID- 25585224
TI  - Why teach an NCLEX prep class?

PMID- 25585225
TI  - Providing culturally proficient care for transgender patients.

PMID- 25585226
TI  - Teaching patients about their short peripheral I.V. catheters.

PMID- 25585227
TI  - Understanding pelvic inflammatory disease.

PMID- 25585228
TI  - When your patient can't read or write.

PMID- 25585230
TI  - Antithrombotic therapy in diabetic patients with coronary artery disease.
AB  - In case of coronary artery disease (CAD), diabetic patients are at higher risk
      than their non-diabetic counterparts. Antithrombotics are therefore of key
      importance to decrease the risk of ischemic complications. A careful assessment
      of the benefit-risk balance is however needed to limit the risk of bleeding.
      Diabetic CAD patients are characterized by a pro-thrombotic milieu and by an
      impaired response to both aspirin and P2Y12 receptor inhibitors, especially to
      clopidogrel. When combined with aspirin, the new P2Y12 receptor inhibitors
      prasugrel and ticagrelor provide superior efficacy for the diabetic patients with
      acute coronary syndromes. In stable CAD, antiplatelet monotherapy (aspirin)
      remains for the time being the reference treatment for diabetic as well as for
      non-diabetic patients; further studies are however ongoing to test whether the
      antithrombotic strategy should be reinforced, particularly in case of diabetes
      mellitus. Finally, although chronic oral anticoagulation is rarely indicated for
      CAD management in itself, it is often prescribed for the concomitant treatment of
      atrial fibrillation. The combination of anticoagulation and antiplatelet therapy
      is associated with a high risk of bleeding and should only be prescribed for
      limited periods of time when the estimated benefits exceed the risks. 

PMID- 25585233
TI  - Three-dimensional graphene-based composites for energy applications.
AB  - Three-dimensional (3D) graphene-based composites have drawn increasing attention
      for energy applications due to their unique structures and properties. By
      combining the merits of 3D graphene (3DG), e.g., a porous and interconnected
      network, a high electrical conductivity, a large accessible surface area, and
      excellent mechanical strength and thermal stability, with the high
      chemical/electrochemical activities of active materials, 3DG-based composites
      show great promise as high-performance electrode materials in various energy
      devices. This article reviews recent progress in 3DG-based composites and their
      applications in energy storage/conversion devices, i.e., supercapacitors, lithium
      ion batteries, dye-sensitized solar cells, and fuel cells. 

PMID- 25585232
TI  - Development of a handheld fluorescence imaging camera for intraoperative sentinel
      lymph node mapping.
AB  - We present a compact fluorescence imaging system developed for real-time sentinel
      lymph node mapping. The device uses two near-infrared wavelengths to record
      fluorescence and anatomical images with a single charge-coupled device camera.
      Experiments on lymph node and tissue phantoms confirmed that the amount of dye in
      superficial lymph nodes can be better estimated due to the absorption correction
      procedure integrated in our device. Because of the camera head's small size and
      low weight, all accessible regions of tissue can be reached without the need for
      any adjustments.

PMID- 25585231
TI  - Sulforaphane and its methylcarbonyl analogs inhibit the LPS-stimulated
      inflammatory response in human monocytes through modulating cytokine production,
      suppressing chemotactic migration and phagocytosis in a NF-kappaB- and MAPK
      dependent manner.
AB  - Sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)-butane], an aliphatic
      isothiocyanate (ITC) naturally derived from cruciferous vegetables and largely
      known for its chemopreventive potential also appears to possess anti-inflammatory
      potential. In this study, structural analogs of SF {compound 1 [1-isothiocyanato
      4-(methylcarbonyl)-butane] and 2 [1-isothiocyanato-3-(methylcarbonyl)-propane]}
      containing a carbonyl group in place of the sulfinyl group in SF, were evaluated
      for their anti-inflammatory activities. In RAW 264.7 cells, the ITCs at non-toxic
      concentrations caused an inhibition of NO and prostaglandin E2 (PGE2) release
      through suppressing expression of inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2), as well as a reduction in matrix metalloproteinase-9
      (MMP-9) expression, secretion and gelatinolytic activity. Further work performed
      on human monocytes isolated from blood of healthy donors revealed that the ITCs
      not only suppressed the expression and release of pro-inflammatory mediators IL
      1beta, IL-6, TNF-alpha and MMP-9, but also suppressed their antibody-independent
      phagocytic and chemotactic migratory abilities. These anti-inflammatory
      activities were mediated through suppression of the NF-kappaB and MAPK signaling
      pathways. In addition, the ITCs were revealed to interact with the cysteines in
      inhibitor of nuclear factor-kappaB kinase beta subunit (IKKbeta), which could
      contribute at least partly to the suppression of NF-kappaB signaling. In
      conclusion, results obtained in this study provide deeper insights into the anti
      inflammatory properties of SF and its methylcarbonyl analogs and the underlying
      mechanisms. These compounds thus serve as promising candidates for clinical
      applications in controlling inflammatory conditions. 

PMID- 25585234
TI  - Weight management-related assessment and counseling by primary care providers in
      an area of high childhood obesity prevalence: current practices and areas of
      opportunity.
AB  - BACKGROUND: Childhood obesity in Georgia exceeds the national rate. The state's
      pediatric primary care providers (PCPs) are well positioned to support behavior
      change, but little is known about provider perceptions and practices regarding
      this role. PURPOSE: The aim of this study was to assess and compare weight
      management-related counseling perceptions and practices among Georgia's PCPs.
      METHODS: In 2012-2013, 656 PCPs (265 pediatricians, 143 family practice
      physicians [FPs], and 248 nurse practitioners/physician assistants [NP/PAs])
      completed a survey regarding weight-management-related practices at well-child
      visits before their voluntary participation in a free training on patient
      centered counseling and child weight management. Data were analyzed in 2014.
      Likert scales were used to quantify responses from 1 (strongly disagree or never)
      to 5 (strongly agree or always). Responses of 4 and 5 responses were combined to
      denote agreement or usual practice. Chi-squared analyses tested for independent
      associations between pediatricians and others. Statistical significance was
      determined using two-sided tests and p value <0.05. RESULTS: The majority of PCPs
      assessed fruit and vegetable intake (83%) and physical activity (78%), but
      pediatricians were more likely than FPs and NP/PAs to assess beverage intake (96%
      vs. 82-87%; p<=0.002) and screen time (86% vs. 74-75%; p<=0.003). Pediatricians
      were also more likely to counsel patients on lifestyle changes (88% vs. 71%;
      p<0.001) and to track progress (50% vs. 35-39%; p<0.05). Though all PCPs agreed
      that goal setting is an effective motivator (88%) and that behavior change
      increases with provider encouragement (85%), fewer were confident in their
      ability to counsel (72%). CONCLUSIONS: Our results show that many PCPS in
      Georgia, particularly pediatricians, have incorporated weight management
      counseling into their practice; however, important opportunities to strengthen
      these efforts by targeting known high-risk behaviors remain.

PMID- 25585247
TI  - Erratum to: "A control systems engineering approach for adaptive behavioral
      interventions: illustration with a fibromyalgia intervention" [Translational
      Behavioral Medicine, Volume 4, Issue 3, pp 275-289].
AB  - [This corrects the article DOI: 10.1007/s13142-014-0282-z.]. 

PMID- 25585246
TI  - A novel mitochondrial carrier protein Mme1 acts as a yeast mitochondrial
      magnesium exporter.
AB  - The homeostasis of magnesium (Mg2+), an abundant divalent cation indispensable
      for many biological processes including mitochondrial functions, is
      underexplored. Previously, two mitochondrial Mg2+ importers, Mrs2 and Lpe10, were
      characterized for mitochondrial Mg2+ uptake. We now show that mitochondrial Mg2+
      homeostasis is accurately controlled through the combined effects of previously
      known importers and a novel exporter, Mme1 (mitochondrial magnesium exporter 1).
      Mme1 belongs to the mitochondrial carrier family and was isolated for its
      mutation that is able to suppress the mrs2Delta respiration defect. Deletion of
      MME1 significantly increased steady-state mitochondrial Mg2+ concentration, while
      overexpression decreased it. Measurements of Mg2+ exit from proteoliposomes
      reconstituted with purified Mme1 provided definite evidence for Mme1 as an Mg2+
      exporter. Our studies identified, for the first time, a mitochondrial Mg2+
      exporter that works together with mitochondrial importers to ensure the precise
      control of mitochondrial Mg2+ homeostasis.

PMID- 25585249
TI  - Mutation stability in primary and metastatic melanoma: what we know and what we
      don't.
AB  - Despite the efficacy and success of targeted therapies, a significant number of
      patients with melanoma exhibit either intrinsic or acquired resistance to these
      drugs. Numerous mechanisms for the development of resistance have been
      postulated, but the precise reason for this is not known. In this review, we
      examine the incidence of mutations in select genes (BRAF, NRAS, C-KIT, and GNAQ)
      known to occur in melanoma, specifically in primary tumors and their paired
      metastases, to understand the significance of intratumoral heterogeneity by
      assessing how changes in mutation status alters the process of metastatic spread.
      Our data revealed a small yet consistent degree of discordance of mutations in
      the MAPK pathway commonly occurring in melanoma indicating that failed targeted
      therapy may be a consequence of this. 

PMID- 25585250
TI  - Exploring valid reference genes for quantitative real-time PCR analysis in
      Sesamia inferens (Lepidoptera: Noctuidae).
AB  - The pink stem borer, Sesamia inferens, which is endemic in China and other parts
      of Asia, is a major pest of rice and causes significant yield loss in this host
      plant. Very few studies have addressed gene expression in S. inferens.
      Quantitative real-time PCR (qRT-PCR) is currently the most accurate and sensitive
      method for gene expression analysis. In qRT-PCR, data are normalized using
      reference genes, which help control for internal differences and reduce error
      between samples. In this study, seven candidate reference genes, 18S ribosomal
      RNA (18S rRNA), elongation factor 1 (EF1), glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), ribosomal protein S13 (RPS13), ribosomal protein S20
      (RPS20), tubulin (TUB), and beta-actin (ACTB) were evaluated for their
      suitability in normalizing gene expression under different experimental
      conditions. The results indicated that three genes (RPS13, RPS20, and EF1) were
      optimal for normalizing gene expression in different insect tissues (head,
      epidermis, fat body, foregut, midgut, hindgut, Malpighian tubules, haemocytes,
      and salivary glands). 18S rRNA, EF1, and GAPDH were best for normalizing
      expression with respect to developmental stages and sex (egg masses; first,
      second, third, fourth, fifth, and sixth instar larvae; male and female pupae; and
      one-day-old male and female adults). 18S rRNA, RPS20, and TUB were optimal for
      fifth instars exposed to different temperatures (-8, -6, -4, -2, 0, and 27
      degrees C). To validate this recommendation, the expression profile of a target
      gene heat shock protein 83 gene (hsp83) was investigated, and results showed the
      selection was necessary and effective. In conclusion, this study describes
      reference gene sets that can be used to accurately measure gene expression in S.
      inferens. 

PMID- 25585248
TI  - Prevention of glucocorticoid induced bone changes with beta-ecdysone.
AB  - Beta-ecdysone (betaEcd) is a phytoecdysteroid found in the dry roots and seeds of
      the asteraceae and achyranthes plants, and is reported to increase osteogenesis
      in vitro. Since glucocorticoid (GC) excess is associated with a decrease in bone
      formation, the purpose of this study was to determine if treatment with betaEcd
      could prevent GC-induced osteoporosis. Two-month-old male Swiss-Webster mice (n=8
      10/group) were randomized to either placebo or slow release prednisolone pellets
      (3.3mg/kg/day) and treated with vehicle control or betaEcd (0.5mg/kg/day) for
      21days. GC treatment inhibited age-dependent trabecular gain and cortical bone
      expansion and this was accompanied by a 30-50% lower bone formation rate (BFR) at
      both the endosteal and periosteal surfaces. Mice treated with only betaEcd
      significantly increased bone formation on the endosteal and periosteal bone
      surfaces, and increased cortical bone mass were their controls to compare to GC
      alone. Concurrent treatment of betaEcd and GC completely prevented the GC-induced
      reduction in BFR, trabecular bone volume and partially prevented cortical bone
      loss. In vitro studies determined that betaEcd prevented the GC increase in
      autophagy of the bone marrow stromal cells as well as in whole bone. In summary,
      betaEcd prevented GC induced changes in bone formation, bone cell viability and
      bone mass. Additional studies are warranted of betaEcd for the treatment of GC
      induced bone loss. 

PMID- 25585251
TI  - Vocabulary relearning in semantic dementia: Positive and negative consequences of
      increasing variability in the learning experience.
AB  - Anomia therapy typically aims to improve patients' communication ability through
      targeted practice in naming a set of particular items. For such interventions to
      be of maximum benefit, the use of trained (or relearned) vocabulary must
      generalise from the therapy setting into novel situations. We investigated
      relearning in three patients with semantic dementia, a condition that has been
      associated with poor generalisation of relearned vocabulary. We tested two
      manipulations designed to improve generalisation of relearned words by
      introducing greater variation into the learning experience. In the first study,
      we found that trained items were retained more successfully when they were
      presented in a variety of different sequences during learning. In the second
      study, we found that training items using a range of different pictured exemplars
      improved the patients' ability to generalise words to novel instances of the same
      object. However, in one patient this came at the cost of inappropriate over
      generalisations, in which trained words were incorrectly used to name
      semantically or visually similar objects. We propose that more variable learning
      experiences benefit patients because they shift responsibility for learning away
      from the inflexible hippocampal learning system and towards the semantic system.
      The success of this approach therefore depends critically on the integrity of the
      semantic representations of the items being trained. Patients with naming
      impairments in the context of relatively mild comprehension deficits are most
      likely to benefit from this approach, while avoiding the negative consequences of
      over-generalisation. 

PMID- 25585252
TI  - Dissolved inorganic carbon enhanced growth, nutrient uptake, and lipid
      accumulation in wastewater grown microalgal biofilms.
AB  - Microalgal biofilms grown to evaluate potential nutrient removal options for
      wastewaters and feedstock for biofuels production were studied to determine the
      influence of bicarbonate amendment on their growth, nutrient uptake capacity, and
      lipid accumulation after nitrogen starvation. No significant differences in
      growth rates, nutrient removal, or lipid accumulation were observed in the algal
      biofilms with or without bicarbonate amendment. The biofilms possibly did not
      experience carbon-limited conditions because of the large reservoir of dissolved
      inorganic carbon in the medium. However, an increase in photosynthetic rates was
      observed in algal biofilms amended with bicarbonate. The influence of bicarbonate
      on photosynthetic and respiration rates was especially noticeable in biofilms
      that experienced nitrogen stress. Medium nitrogen depletion was not a suitable
      stimulant for lipid production in the algal biofilms and as such, focus should be
      directed toward optimizing growth and biomass productivities to compensate for
      the low lipid yields and increase nutrient uptake. 

PMID- 25585253
TI  - Harvesting carbohydrate-rich Arthrospira platensis by spontaneous settling.
AB  - The filamentous cyanobacterium Arthrospira platensis is an attractive feedstock
      for carbohydrate-based biofuels because it accumulated up to 74% of carbohydrates
      when nitrogen stressed. Nitrogen stressed A. platensis also settled
      spontaneously, and this occurred simultaneously with carbohydrates accumulation,
      suggesting a link between both phenomena. The increased settling velocity was
      neither due to production of extracellular carbohydrates, nor due to degradation
      of gas vacuoles, but was caused by an increase in the specific density of the
      filaments as a result of accumulation of carbohydrates under the form of
      glycogen. Settling velocities of carbohydrate-rich A. platensis reached 0.64mh(
      1), which allowed the biomass to be harvested using a lamella separator. The
      biomass could be concentrated at least 15 times, allowing removal of 94% of the
      water using gravity settling, thus offering a potential application as a low-cost
      and high-throughput method for primary dewatering of carbohydrate-rich A.
      platensis. 

PMID- 25585254
TI  - Biodiesel production from microalgae oil catalyzed by a recombinant lipase.
AB  - A recombinant Rhizomucor miehei lipase was constructed and expressed in Pichia
      pastoris. The target enzyme was termed Lipase GH2 and it can be used as a free
      enzyme for catalytic conversion of microalgae oil mixed with methanol or ethanol
      for biodiesel production in an n-hexane solvent system. Conversion rates of two
      major types of biodiesel, fatty acid methyl ester (FAME) and fatty acid ethyl
      ester (FAEE), reached maximal values (>90%) after 24h. The process of FAME
      production is generally more simple and economical than that of FAEE production,
      even though the two processes show similar conversion rates. In spite of the
      damaging effect of ethanol on enzyme activity, we successfully obtained ethyl
      ester by the enzymatic method. Our findings indicate that Lipase GH2 is a useful
      catalyst for conversion of microalgae oil to FAME or FAEE, and this system
      provides efficiency and reduced costs in biodiesel production. 

PMID- 25585255
TI  - 4-Vinylphenol biosynthesis from cellulose as the sole carbon source using
      phenolic acid decarboxylase- and tyrosine ammonia lyase-expressing Streptomyces
      lividans.
AB  - Streptomyces lividans was adopted as a host strain for 4-vinylphenol (4VPh)
      production directly from cellulose. In order to obtain novel phenolic acid
      decarboxylase (PAD) expressed in S. lividans, PADs distributed among Streptomyces
      species were screened. Three novel PADs, derived from Streptomycessviceus,
      Streptomyceshygroscopicus, and Streptomycescattleya, were successfully obtained
      and expressed in S. lividans. S. sviceus PAD (SsPAD) could convert p
      hydroxycinnamic acid (pHCA) to 4VPh more efficiently than the others both in
      vitro and in vivo. For 4VPh production directly from cellulose, l-tyrosine
      ammonia lyase derived from Rhodobacter sphaeroides and SsPAD were introduced into
      endoglucanase-secreting S. lividans, and the 4VPh biosynthetic pathway was
      constructed therein. The created transformants successfully produced 4VPh
      directly from cellulose. 

PMID- 25585256
TI  - Optimization and evaluation of alkaline potassium permanganate pretreatment of
      corncob.
AB  - Alkaline potassium permanganate solution (APP) was applied to the pretreatment of
      corncob with a simple and effective optimization of APP concentration, reaction
      time, temperature and solid to liquid ratio (SLR). The optimized pretreatment
      conditions were at 2% (w/v) potassium permanganate with SLR of 1:10 treating for
      6h at 50 degrees C. This simple one-step treatment resulted in significant 94.56%
      of the cellulose and 81.47% of the hemicellulose recoveries and 46.79% of the
      lignin removal of corncob. The reducing sugar in the hydrolysate from APP
      pretreated corncob was 8.39g/L after 12h enzymatic hydrolysis, which was 1.44 and
      1.29 folds higher than those from raw and acid pretreated corncobs. Physical
      characteristics, crystallinity and structure of the pretreated corncob were
      analyzed and assessed by SEM, XRD and FTIR. The APP pretreatment process was
      novel and enhanced enzymatic hydrolysis of lignocellulose by affecting
      composition and structural features. 

PMID- 25585257
TI  - Pyrolysis behaviors and kinetics of refining and chemicals wastewater, lignite
      and their blends through TGA.
AB  - Co-pyrolysis behaviors of refining and chemicals wastewater solid (RS) and
      Huolinhe lignite (HL) were investigated via thermogravimetric analysis (TGA). The
      thermal degradation process of RS and the blends proceeded in three stages, while
      two stages for HL. The increased percentage of RS in the blends reduced the
      characteristic temperature (Ti, Tp, Tf) and residual mass (Mr), while raised the
      characteristic reaction rate (Rp, Rv) and comprehensive devolatilization
      parameter (D). The results indicated that there existed some inhibitive
      interactions between RS and HL. The activation energies were calculated by using
      the Friedman and Starink method. The activation energy of RS increased first and
      then decreased with conversion degree, and the variation wasn't as great as that
      of the blends and lignite. No matter which conversion degree is, the activation
      energy decreased with the percentage of RS in the blends increasing. The minimum
      value was obtained by blending 75wt.% RS. 

PMID- 25585258
TI  - Enhanced lipid production with undetoxified corncob hydrolysate by Rhodotorula
      glutinis using a high cell density culture strategy.
AB  - In recent years, energy crisis and environmental issues such as greenhouse
      effect, global warming, etc. has roused peoples' concern. Biodiesel, as renewable
      energy, has attracted much attention to deal with such problems. This work
      studied the lipid production by Rhodotorula glutinis with undetoxified corncob
      hydrolysate. The results indicated that R. glutinis had high tolerance to the
      inhibitors in corncob hydrolysate and it could utilize undetoxified corncob
      hydrolysate directly for lipid production. The cell grew well with undetoxified
      hydrolysate in the batch culture of 5L fermentor with the optimized C/N ratio of
      75, lipid titer and lipid content reached 5.5g/L and 36.4%, respectively. High
      cell density culture with two-stage nitrogen feeding strategy was studied to
      enhance the lipid production, biomass, lipid concentration and lipid content of
      70.8, 33.5g/L and 47.2% were obtained. The results indicated the potential
      application for lipid production by R. glutinis with corncob hydrolysate
      directly. 

PMID- 25585259
TI  - Composting of food waste subjected to hydrothermal pretreatment and inoculated
      with Paecilomyces sp. FA13.
AB  - Food waste collected from restaurants, convenience stores, and food-processing
      factories was mixed with sawdust and subjected to hydrothermal pretreatment at
      180 degrees C for 30min to prepare compost raw material. Furan compounds such as
      5-HMF (5-hydroxymethyl furfural) and furfural were produced at concentration
      levels of approximately 8 and 0.5mg/g-ds, respectively, through hydrothermal
      pretreatment. The furan compounds inhibited the activity of composting
      microorganisms, thus delaying the start of organic matter degradation during
      composting. A newly identified fungus, Paecilomyces sp. FA13, which possesses the
      ability to degrade furan compounds, was isolated and used as an inoculum for the
      composting of the raw material prepared by hydrothermal pretreatment. By
      inoculating the FA13 into the compost raw material at 10(5)CFU/g-ds, the
      degradation of furan compounds was accelerated. As a result, bacterial activity,
      which contributed to composting, was enhanced, significantly promoting the start
      of vigorous degradation of organic materials. 

PMID- 25585260
TI  - Molecular imaging in cardiovascular diseases.
AB  - Cardiovascular diseases remain the leading cause of morbidity and mortality in
      industrialized and developing countries. In clinical practice, the in-vivo
      identification of atherosclerotic lesions, which can lead to complications such
      as heart attack or stroke, remains difficult. Imaging techniques provide the
      reference standard for the detection of clinically significant atherosclerotic
      changes in the coronary and carotid arteries. The assessment of the luminal
      narrowing is feasible, while the differentiation of stable and potentially
      unstable or vulnerable atherosclerotic plaques is currently not possible using
      non-invasive imaging. With high spatial resolution and high soft tissue contrast,
      magnetic resonance imaging (MRI) is a suitable method for the evaluation of the
      thin arterial wall. In clinical practice, native MRI of the vessel wall already
      allows the differentiation and characterization of components of atherosclerotic
      plaques in the carotid arteries and the aorta. Additional diagnostic information
      can be gained by the use of non-specific MRI contrast agents. With the
      development of targeted molecular probes, that highlight specific molecules or
      cells, pathological processes can be visualized at a molecular level with high
      spatial resolution. In this review article, the development of pathophysiological
      changes leading to the development of the arterial wall are introduced and
      discussed. Additionally, principles of contrast enhanced imaging with non
      specific contrast agents and molecular probes will be discussed and latest
      developments in the field of molecular imaging of the vascular wall will be
      introduced.

PMID- 25585262
TI  - Update on neuromuscular diseases: Pathology and molecular pathogenesis.

PMID- 25585263
TI  - A suction blister model reliably assesses skin barrier restoration and immune
      response.
AB  - Skin wound healing models can be used to detect changes in immune function in
      response to interventions. This study used a test-retest format to assess the
      reliability of a skin suction blister procedure for quantitatively evaluating
      human immune function in repeated measures type studies. Up to eight suction
      blisters (~30 mm(2)) were induced via suction on each participant's left and
      right forearm (randomized order; blister session 1 and 2), separated by
      approximately one week. Fluid was sampled from each blister, and the top layer of
      each blister was removed to reveal up to eight skin wounds. Fluid from each wound
      was collected 4, 7 and 24h after blisters were induced, and proinflammatory
      cytokines were measured. Transepidermal water loss (TEWL), to assess skin barrier
      recovery, was measured daily at each wound site until values were within 90% of
      baseline values (i.e., unbroken skin). Sleep, stress and inflammation (i.e.,
      factors that affect wound healing and immune function), preceding the blister
      induction, were assessed via activity monitors (Actical, Philips Respironics,
      Murrysville, Pennsylvania), the Perceived Stress Scale (PSS) and C-reactive
      protein (CRP), respectively. Area-under-the-curve and TEWL, between blister
      session 1 and 2, were compared using Pearson correlations and partial
      correlations (controlling for average nightly sleep, PSS scores and CRP). The
      suction blister method was considered reliable for assessing immune response and
      skin barrier recovery if correlation coefficients reached 0.7. Volunteers (n=16;
      12 M; 4F) were 23 +/- 5 years [mean +/- SD]. Time to skin barrier restoration was
      4.9 +/- 0.8 and 4.8 +/- 0.9 days for sessions 1 and 2, respectively. Correlation
      coefficients for skin barrier restoration, IL-6, IL-8 and MIP-1alpha were 0.9
      (P<0.0001), 0.7 (P=0.008) and 0.9 (P<0.0001), respectively. When average nightly
      sleep, PSS scores and CRP (i.e., percent difference between sessions 1 and 2)
      were taken into consideration, correlations in immune response between sessions 1
      and 2 were improved for IL-8 (0.8, P=0.002) and TNF-alpha (0.7, P=0.02). The skin
      suction blister method is sufficiently reliable for assessing skin barrier
      restoration and immune responsiveness. This data can be used to determine sample
      sizes for cross-sectional or repeated-measures types of studies testing the
      impact of various stressors on immune response, and/or the efficacy of
      interventions to mitigate decrements in immune response to stress.

PMID- 25585261
TI  - Inflaming the diseased brain: a role for tainted melanins.
AB  - Inflammation plays a crucial role in neurodegenerative diseases, but the
      irritants responsible for this response remain largely unknown. This report
      addressed the hypothesis that hypochlorous acid reacts with dopamine to produce
      melanic precipitates that promote cerebral inflammation. Spectrophotometric
      studies demonstrated that nM amounts of HOCl and dopamine react within seconds. A
      second-order rate constant for the reaction of HOCl and dopamine of 2.5 * 10(4)M(
      1)s(-1) was obtained by measuring loss of dopaminergic fluorescence due to HOCl.
      Gravimetric measurements, electron microscopy, elemental analysis, and a novel
      use of flow cytometry confirmed that the major product of this reaction is a
      precipitate with an average diameter of 1.5 MUm. Flow cytometry was also used to
      demonstrate the preferential reaction of HOCl with dopamine rather than albumin.
      Engulfment of the chlorodopamine particulates by phagocytes in vitro caused these
      cells to release TNFalpha and die. Intrastriatal administration of 10(6)
      particles also increased the content of TNFalpha in the brain and led to a 50%
      loss of the dopaminergic neurons in the nigra. These studies indicate that HOCl
      and dopamine react quickly and preferentially with each other to produce
      particles that promote inflammation and neuronal death in the brain.

PMID- 25585264
TI  - Statistical estimation of antibody concentration using multiple dilutions.
AB  - In medicine and chemistry, measurement of concentrations usually involves
      calibration that maps the observed responses to the underlying concentration
      using inversion of a standard curve. The Enzyme-linked ImmunoSorbent Assay
      (ELISA) is one example of such methods that is commonly used to measure antibody
      concentration. A problem in this and similar type of technology is that an
      accurate measurement is obtainable only if the observations fall within the
      optimal, near-linear range of the standard curve. It is common to conduct a
      series of doubling or tripling dilutions of the samples, so that at least some of
      the diluted samples are within the optimal range. A single dilution may then be
      selected for statistical analysis. This common practice does not fully utilize
      the data from multiple dilutions and reduces accuracy. We consider two weighted
      average estimators for fully utilizing the information from multiple dilutions.
      The first uses weights inversely proportional to the variances of the dilution
      specific calibrated values; the second is a simplified form of the first.
      Simulation results demonstrated the superiority of this weighted estimation
      approach over the conventional approach of analyzing a single selected dilution.
      We apply the methods to an experimental study of malaria vaccine candidates. 

PMID- 25585265
TI  - Oxidative stress in COPD: molecular background and clinical monitoring.
AB  - Chronic obstructive pulmonary disease (COPD) is a major and rapidly increasing
      health problem associated with a chronic inflammatory response, predominantly in
      small airways and lung parenchyma. Oxidative stress induced by reactive oxygen
      and nitrogen species (ROS and RNS) plays a central role in the pathophysiology of
      COPD. There is evidence that several molecules formed during oxidative processes
      may have the potential to serve as biomarkers of oxidative stress in the airways
      of patients with COPD. Among these molecules carbon monoxide, ethane and pentane
      can be measured in the exhaled air, while 8-isoprostane, malondialdehyde, 4-
      hydroxyhexenal, 4-hyroxynonenal, acrolein, hydrogen peroxide, nitrogen oxides and
      3-nitrotyrosine can be detected in exhaled breath condensate and/or sputum
      supernatant. In this review the molecular background of these processes including
      the formation of ROS and RNS, the biosynthesis of essential omega-3 and omega-6
      polyunsaturated fatty acids as building blocks of lipids in the cellular
      membranes and their enzymatic and non-enzymatic metabolism to eicosanoids and
      related compounds have been summarized. Moreover, the formation of oxidative
      stress markers studied most commonly in the context of COPD has been briefly
      discussed. The associations between biomarkers and clinical variables have also
      been highlighted in an attempt to illustrate the potential clinical applicability
      of these biomarker measurements. 

PMID- 25585266
TI  - Removal of perfluorinated carboxylates from washing wastewater of
      perfluorooctanesulfonyl fluoride using activated carbons and resins.
AB  - Perfluorooctanesulfonyl fluoride (PFOSF) washing wastewater contains high
      concentrations of perfluorinated carboxylates (PFCAs) including
      perfluorohexanoate (PFHxA, 0.10 mmol/L), perfluoroheptanoate (PFHpA, 0.11
      mmol/L), and perfluorooctanoate (PFOA, 0.29 mmol/L). For the first time, we
      investigated the removal of these PFCAs from actual wastewater using the bamboo
      derived activated carbon (BAC) and resin IRA67. Adsorption kinetics, effects of
      adsorbent dose, solution pH, and inorganic ions, as well as regeneration and
      reuse experiments were studied. The removal percents of three PFCAs by BAC and
      IRA67 followed the increasing order of PFHxA < PFHpA < PFOA, but the adsorption
      equilibrium time conformed to the reverse trend. PFCAs removal on IRA67 decreased
      with increasing pH, but BAC almost kept stable PFCAs removal at pH above 5.0.
      Among competitive adsorption of three PFCAs, PFOA was preferentially adsorbed on
      both BAC and IRA67. PFCAs removal from actual wastewater by BAC was higher than
      that in simulated solution, due to the presence of high concentration of
      inorganic ions in the wastewater. However, the co-existing organic compounds in
      wastewater significantly suppressed the adsorption of PFCAs. Both spent BAC and
      IRA67 were successfully regenerated by ethanol solution or NaCl/methanol mixture,
      and IRA67 showed the stable removal of PFCAs in five adsorption cycles.

PMID- 25585267
TI  - Facile synthesis of amino-functionalized titanium metal-organic frameworks and
      their superior visible-light photocatalytic activity for Cr(VI) reduction.
AB  - Porous metal-organic frameworks (MOFs) have been arousing a great interest in
      exploring the application of MOFs as photocatalyst in environment remediation. In
      this work, two different MOFs, Ti-benzenedicarboxylate (MIL-125(Ti)) and amino
      functionalized Ti-benzenedicarboxylate (NH2-MIL-125(Ti)) were successfully
      synthesized via a facile solvothermal method. The MIL-125(Ti) and NH2-MIL-125(Ti)
      were well characterized by XRD, SEM, XPS, N2 adsorption-desorption measurements,
      thermogravimetric analysis and UV-vis diffuse reflectance spectra (DRS). It is
      revealed that the NH2-MIL-125(Ti) has well crystalline lattice, large surface
      area and mesoporous structure, chemical and thermal stability, and enhanced
      visible-light absorption up to 520 nm, which was associated with the chromophore
      (amino group) in the organic linker. Compared with MIL-125(Ti), NH2-MIL-125(Ti)
      exhibited more efficient photocatalytic activity for Cr(VI) reduction from
      aqueous solution under visible-light irradiation. The addition of hole scavenger,
      the hole scavenger concentration and the pH value of the reaction solution played
      important roles in the photo-catalytic reduction of Cr(VI). The presence of
      Ti(3+)-Ti(4+) intervalence electron transfer was the main reason for photo
      excited electrons transportation from titanium-oxo clusters to Cr(VI),
      facilitating the Cr(VI) reduction under the acid condition. It was demonstrated
      that amino-functionalized Ti(IV)-based MOFs could be promising visible-light
      photocatalysts for the treatment of Cr(VI)-contained wastewater.

PMID- 25585268
TI  - As-synthesized multi-walled carbon nanotubes for the removal of ionic and non
      ionic surfactants.
AB  - This research deals with the application of untreated multi-walled carbon
      nanotubes (MWCNT) in their agglomerates form for the removal of non-ionic (TX
      100), cationic (CTAB) and anionic (SDBS) surfactants from aqueous media. In order
      to optimize the removal process, the influence of several key parameters was
      investigated including contact time under different solid/liquid ratios, initial
      solution pH, temperature, along with ultrasonication assistance and desorption
      assays. Experimentations revealed that pH variation enhanced the removal
      capacities at optimum values of 6, 2 and 8 for TX-100, SDBS and CTAB,
      respectively, and that hydrophobic interaction is a major adsorption factor,
      especially for non-ionic surfactant with possible electrostatic interactions
      occurring for the ionic ones. As well, removal efficiencies peaked for an optimum
      temperature range between 35 and 45  degrees C. As for the ultrasonication
      assistance, it enhanced the overall removal capacities, especially that of the
      ionic surfactant, with an enhancement of 52% for the case of SDBS after 1h of
      treatment. The modeling results revealed that the pseudo-second order model
      provided the best correlation of the dynamic data and that the process was
      controlled by intraparticle diffusion phenomena. At equilibrium, and under
      optimized experimental conditions, untreated MWCNTs showed promising removal
      capacities with 359, 312 and 156 mg/g for TX-100, SDBS and CTAB, respectively.

PMID- 25585269
TI  - Fe3O4 and MnO2 assembled on honeycomb briquette cinders (HBC) for arsenic removal
      from aqueous solutions.
AB  - In this study, a novel composite adsorbent (HBC-Fe3O4-MnO2) was synthesized by
      combining honeycomb briquette cinders (HBC) with Fe3O4 and MnO2 through a co
      precipitation process. The purpose was to make the best use of the oxidative
      property of MnO2 and the adsorptive ability of magnetic Fe3O4 for enhanced
      As(III) and As(V) removal from aqueous solutions. Experimental results showed
      that the adsorption capacity of As(III) was observed to be much higher than
      As(V). The maximum adsorption capacity (2.16 mg/g) was achieved for As(III) by
      using HBC-Fe3O4-MnO2 (3:2) as compared to HBC-Fe3O4-MnO2 (2:1) and HBC-Fe3O4-MnO2
      (1:1). The experimental data of As(V) adsorption fitted well with the Langmuir
      isotherm model, whereas As(III) data was described perfectly by Freundlich model.
      The pseudo-second-order kinetic model was fitted well for the entire adsorption
      process of As(III) and As(V) suggesting that the adsorption is a rate-controlling
      step. Aqueous solution pH was found to greatly affect the adsorption behavior.
      Furthermore, co-ions including HCO3(-) and PO4(3-) exhibited greater influence on
      arsenic removal efficiency, whereas Cl(-), NO3(-), SO4(2-) were found to have
      negligible effects on arsenic removal. Five consecutive adsorption-regeneration
      cycles confirmed that the adsorbent could be reusable for successive arsenic
      treatment and can be used in real treatment applications.

PMID- 25585271
TI  - Innovative delivery of pain management interventions: current trends and future
      progress.

PMID- 25585270
TI  - SCN9A Variants May be Implicated in Neuropathic Pain Associated With Diabetic
      Peripheral Neuropathy and Pain Severity.
AB  - OBJECTIVES: Previous studies have established the role of SCN9A in various pain
      conditions, including idiopathic small fiber neuropathy. In the present study, we
      interrogate the relationship between common and rare variants in SCN9A gene and
      chronic neuropathic pain associated with diabetic peripheral neuropathy. DESIGN:
      Using a cohort of 938 patients of European ancestry with chronic neuropathic pain
      associated with diabetic peripheral neuropathy enrolled in 6 clinical studies and
      2 controls (POPRES, n=2624 and Coriell, n=1029), we examined the relationship
      between SCN9A variants and neuropathic pain in a case-control study using a 2
      stage design. The exonic regions of SCN9A were sequenced in a subset of 244
      patients with neuropathic pain, and the variants discovered were compared with
      POPRES control (stage 1). The top associated variants were followed up by
      genotyping in the entire case collection and Coriell controls restricting the
      analysis to the matching patients from the United States and Canada only (stage
      2). RESULTS: Seven variants were found to be associated with neuropathic pain at
      the sequencing stage. Four variants (Asp1908Gly, Val991Leu/Met932Leu, and an
      intronic variant rs74449889) were confirmed by genotyping to occur at a higher
      frequency in cases than controls (odds ratios ~2.1 to 2.6, P=0.05 to 0.009).
      Val991Leu/Met932Leu was also associated with the severity of pain as measured by
      pain score Numeric Rating Scale (NRS-11, P=0.047). Val991Leu/Met932Leu variants
      were in complete linkage disequilibrium and previously shown to cause
      hyperexcitability in dorsal root ganglia neurons. CONCLUSIONS: The association of
      SCN9A variants with neuropathic pain and pain severity suggests a role of SCN9A
      in the disease etiology of neuropathic pain.

PMID- 25585272
TI  - Efficacy and Cost-effectiveness of Acceptance and Commitment Therapy and Applied
      Relaxation for Longstanding Pain: A Randomized Controlled Trial.
AB  - BACKGROUND AND OBJECTIVES: To date, few studies have compared Acceptance and
      Commitment Therapy (ACT) for longstanding pain with established treatments. Only
      1 study has evaluated the cost-effectiveness of ACT. The aim of the current study
      was to evaluate the efficacy and cost-effectiveness of ACT and applied relaxation
      (AR) for adults with unspecific, longstanding pain. MATERIALS AND METHODS: On the
      basis of the inclusion criteria 60 consecutive patients received 12 weekly group
      sessions of ACT or AR. Data were collected pretreatment, midtreatment, and
      posttreatment, as well as at 3- and 6-month follow-up. Growth curve modeling was
      used to analyze treatment effects on pain disability, pain intensity, health
      related quality of life (physical domain), anxiety, depression, and acceptance.
      RESULTS: Significant improvements were seen across conditions (pretreatment to
      follow-up assessment) on all outcome measures. Pain disability decreased
      significantly in ACT relative to AR from preassessment to postassessment. A
      corresponding decrease in pain disability was seen in AR between postassessment
      and 6-month follow-up. Pain acceptance increased only in ACT, and this effect was
      maintained at 6-month follow-up. Approximately 20% of the participants achieved
      clinically significant change after treatment. Health economic analyses showed
      that ACT was more cost-effective than AR at post and 3-month follow-up
      assessment, but not at 6-month follow-up. DISCUSSION: More studies investigating
      moderators and mediators of change are needed. The present study is one of few
      that have evaluated the cost-effectiveness of ACT and AR and compared ACT with an
      established behavioral intervention, and the results provide additional support
      for behavioral interventions for longstanding pain.

PMID- 25585273
TI  - Light and chemically driven molecular machines showing a unidirectional four
      state switching cycle.
AB  - The imitation of macroscopic movements at the molecular level is a key step in
      the development of nanomachines. The challenge is the synthesis of molecules that
      are able to transform external stimuli into a direction-controlled mechanical
      movement. The more complex such motion sequences are, the more difficult is the
      construction of the corresponding nanomachine. Here, we present a system that
      demonstrates a unidirectional, four-state switching cycle that bears similar
      characteristics to the arm movements of a human breaststroke swimmer. Like the
      latter, the molecules have a torso and two arms. The arms consist of bipyridine
      units and can be folded and stretched by addition and removal of copper ions. The
      unidirectional rotation of the arms is achieved by light-induced switching of an
      azo unit. 

PMID- 25585274
TI  - Bloodstream infections in adult patients undergoing cord blood transplantation
      from unrelated donors after myeloablative conditioning regimen.
AB  - The incidence, epidemiology, and risk factors of bloodstream infection (BSI) and
      their impact on transplant outcomes after umbilical cord blood transplantation
      (UCBT) are not well defined. Between May 1997 and December 2012, 202 isolates in
      189 episodes of BSI were registered in 134 of 241 patients who underwent single
      unit myeloablative UCBT. Cumulative incidence (CI) of developing at least 1
      episode of BSI was 21%, 29%, 34%, 42%, and 52% at days +7, +14, +30, +100, and
      +365, respectively. The median time of onset for the first BSI episode was day
      +10 (range, day -7 to +1217). Early BSI before day 7 was associated with
      increased nonrelapse mortality (relative risk [RR], 1.5; 95% confidence interval
      [CI], 1.1 to 2.3; P = .04), whereas BSI before day 14 was an independent adverse
      risk factor for neutrophil recovery (RR, .6; 95% CI, .5 to .9; P = .002). A
      higher CD8(+) cell dose of the graft was the only variable independently
      associated with reduced risk of BSI (RR, .1; 95% CI, .02 to .7; P = .02). The
      gram-negative rod (GNR) to gram-positive bacteria ratio was .9 before day +30 and
      1.6 thereafter (P = .03). Escherichia coli (31%) and Pseudomonas sp. (28%) were
      the most frequently isolated among GNR. The overall crude mortality rate was 12%
      at day 7 and was higher for GNR (18%) compared with gram-positive bacteria (7%)
      (P = .03). These findings emphasize the importance of preventing bacterial
      infections during conditioning and the very early post-UCBT period.

PMID- 25585277
TI  - The LATL as locus of composition: MEG evidence from English and Arabic.
AB  - Neurolinguistic investigations into the processing of structured sentences as
      well as simple adjective-noun phrases point to the left anterior temporal lobe
      (LATL) as a leading candidate for basic linguistic composition. Here, we
      characterized the combinatory profile of the LATL over a variety of syntactic and
      semantic environments, and across two languages, English and Arabic. The
      contribution of the LATL was investigated across two types of composition: the
      optional modification of a predicate (modification) and the satisfaction of a
      predicate's argument position (argument saturation). Target words were presented
      during MEG recordings, either in combinatory contexts (e.g. "eats meat") or in
      non-combinatory contexts (preceded by an unpronounceable consonant string, e.g.
      "xqkr meat"). Across both languages, the LATL showed increased responses to words
      in combinatory contexts, an effect that was robust to composition type and word
      order. Together with related findings, these results solidify the role of the
      LATL in basic semantic composition. 

PMID- 25585275
TI  - A refined risk score for acute graft-versus-host disease that predicts response
      to initial therapy, survival, and transplant-related mortality.
AB  - To develop a novel acute graft-versus-host disease (GVHD) risk score, we examined
      the GVHD clinical stage and grade of 1723 patients at the onset of treatment with
      systemic steroids. Using clinical grouping, descriptive statistics and recursive
      partitioning, we identified poorly responsive, high-risk (HR) acute GVHD by the
      number of involved organs and severity of GVHD at onset. The overall response
      (complete response/partial response) rate 28 days after initiation of steroid
      therapy for acute GVHD was lower in the 269 patients with HR-GVHD than in the
      1454 patients with standard risk (SR)-GVHD (44% [95% confidence interval (CI) 38%
      to 50%] versus 68% [95% CI, 66% to 70%], P < .001). Patients with HR-GVHD were
      less likely to respond at day 28 (odds ratio [OR], .3; 95% CI, .2 to .4; P <
      .001) and had higher risks of mortality (relative risk, 2.1; 95% CI, 1.7 to 2.6;
      P < .001) and transplant-related mortality (relative risk, 2.5; 95% CI, 2.0% to
      3.2%, P < .001) than patients with SR-GVHD. This refined definition of acute GVHD
      risk is a better predictor of response, survival, and transplant-related
      mortality than other published acute GVHD risk scores. Patients with HR-GVHD are
      candidates for studies investigating new treatment approaches. Likewise, patients
      with SR-GVHD are candidates for studies investigating less toxic therapy.

PMID- 25585276
TI  - Skill dependent audiovisual integration in the fusiform induces repetition
      suppression.
AB  - Learning to read entails mapping existing phonological representations to novel
      orthographic representations and is thus an ideal context for investigating
      experience driven audiovisual integration. Because two dominant brain-based
      theories of reading development hinge on the sensitivity of the visual-object
      processing stream to phonological information, we were interested in how reading
      skill relates to audiovisual integration in this area. Thirty-two children
      between 8 and 13 years of age spanning a range of reading skill participated in a
      functional magnetic resonance imaging experiment. Participants completed a rhyme
      judgment task to word pairs presented unimodally (auditory- or visual-only) and
      cross-modally (auditory followed by visual). Skill-dependent sub-additive
      audiovisual modulation was found in left fusiform gyrus, extending into the
      putative visual word form area, and was correlated with behavioral orthographic
      priming. These results suggest learning to read promotes facilitatory audiovisual
      integration in the ventral visual-object processing stream and may optimize this
      region for orthographic processing.

PMID- 25585278
TI  - Effect of human isolated probiotic bacteria on preventing Campylobacter jejuni
      colonization of poultry.
AB  - This study was performed in order to determine whether human isolated probiotic
      bacteria can be effective in reducing Campylobacter jejuni infection of chicken
      intestinal cells, in vitro, and in decreasing its colonization abilities within
      the chicken gut. Our results show that the probiotic strains Lactobacillus
      paracasei J. R, L. rhamnosus 15b, L. lactis Y, and L. lactis FOa had a
      significant effect on C. jejuni invasion of chicken primary cells, with the
      strongest inhibitory effect detected when a combination of four was administered.
      In regard to the in vivo effect, using all four strains in one combination
      prevented mucus colonization in the duodenum and cecum. Moreover, the pathogen
      load in the lumen of these two compartments was significantly reduced. When
      probiotics were introduced during the early growth period, the presence of the
      pathogen in feces was increased (p>0.05), but when they were given during the
      last week of growth, there was no significant effect. In conclusion, our data
      indicate that these four new probiotic strains are able to cause modifications in
      the chicken intestinal mucosa and can reduce the ability of C. jejuni to invade,
      in vitro, and to colonize, in vivo. These probiotics are now proven to be
      effective even when introduced in broiler's feed 7 days before slaughter, which
      makes them cost-effective for the producers.

PMID- 25585281
TI  - Synthesis of buoyant metal-coated fly ash cenosphere and its excellent catalytic
      performance in dye degradation.
AB  - In this work, Ag(+) and Ag(0) were absorbed onto the surface of 3
      mercaptopropyltriethoxysilane modified fly ash cenospheres (FACs) in two Ag
      activation processes. The activation methods, avoiding traditional surface
      sensitization by SnCl2, successfully initiated electroless copper particles
      deposition for the preparation of buoyant Cu-FAC and CuAg-FAC composites. The
      CuAg-FAC had a much more uniform morphology than the Cu-FAC. The catalytic
      performance of the Cu-FAC and CuAg-FAC was examined by the reduction of Orange IV
      azo dye with the presence of NaBH4. 98.4% of Orange IV was rapidly reduced within
      25 min by the CuAg-FAC, whereas 76.4% of Orange IV was removed by the Cu-FAC. The
      results reveal that the degradation processes matched well with the pseudo-first
      order kinetics model, and rate constants of 0.057 and 0.186 min(-1) were obtained
      for the Cu-FAC and CuAg-FAC, respectively. Moreover, two other dyes of Orange II
      and Reactive Black 5 were also efficiently reduced by the CuAg-FAC which could be
      easily recycled and stably reused at least four times. These buoyant metal-coated
      FAC composites would be very useful in various catalytic reductions.

PMID- 25585280
TI  - Tailored synthesis of amine N-halamine copolymerized polystyrene with capability
      of killing bacteria.
AB  - Novel amine N-halamine copolymerized polystyrene (ANHCPS) nanostructures were
      controllably fabricated as potent antibiotics by using the surfactant-free
      emulsion copolymerization for killing pathogenic bacteria. The morphology and
      size of the ANHCPS were well tailored by tuning reaction conditions such as
      monomer molar ratio, temperature, and copolymerization time. Effect of
      chlorination aging time on the oxidative chlorine content in the ANHCPS was
      established, and the oxidative chlorine content was determined by the modified
      iodometric/thiosulfate technique. Antibacterial behavior of the ANHCPS on
      bacterial strain was evaluated using Staphylococcus aureus and Escherichia coli
      as model pathogenic bacteria via the plate counting technique, inhibition zone
      study, and time-kill assay. Antimicrobial results illustrated that the ANHCPS
      possessed superior antibacterial capability of killing pathogenic bacteria. The
      destruction induced by the ANHCPS on bacterial surface structure was proven by
      using SEM technique. The effect of the oxidative chlorine content and
      morphology/size on the antimicrobial capability was constructed as well. This
      study provides us a novel approach for controllably synthesizing amine N-halamine
      polymers, and making them the potent candidates for killing bacteria or even the
      control of microorganism contamination.

PMID- 25585279
TI  - Multiple nanosecond electric pulses increase the number but not the size of long
      lived nanopores in the cell membrane.
AB  - Exposure to intense, nanosecond-duration electric pulses (nsEP) opens small but
      long-lived pores in the plasma membrane. We quantified the cell uptake of two
      membrane integrity marker dyes, YO-PRO-1 (YP) and propidium (Pr) in order to test
      whether the pore size is affected by the number of nsEP. The fluorescence of the
      dyes was calibrated against their concentrations by confocal imaging of stained
      homogenates of the cells. The calibrations revealed a two-phase dependence of Pr
      emission on the concentration (with a slower rise at<4MUM) and a linear
      dependence for YP. CHO cells were exposed to nsEP trains (1 to 100 pulses, 60ns,
      13.2kV/cm, 10Hz) with Pr and YP in the medium, and the uptake of the dyes was
      monitored by time-lapse imaging for 3min. Even a single nsEP triggered a modest
      but detectable entry of both dyes, which increased linearly when more pulses were
      applied. The influx of Pr per pulse was constant and independent of the pulse
      number. The influx of YP per pulse was highest with 1- and 2-pulse exposures,
      decreasing to about twice the Pr level for trains from 5 to 100 pulses. The
      constant YP/Pr influx ratio for trains of 5 to 100 pulses suggests that
      increasing the number of pulses permeabilizes cells to a greater extent by
      increasing the pore number and not the pore diameter. 

PMID- 25585282
TI  - Preparation and analytical application of the novel Hg(II)-selective membrane
      electrodes based on oxime compounds.
AB  - Novel Hg(II)-selective poly(vinyl) chloride (PVC) membrane electrodes based on
      oxime compounds of (4-(4-methylphenylaminoisonitrosoacetyl)biphenyl, I1; 4-(4
      clorophenylaminoisonitrosoacetyl)biphenyl, I2; N,N-bis[1-(4-phenylphenyl)-2
      hydroxyimino-2-(4-chloroaniline)-1-ethylidene]-diethylenetriamine, I3 and N,N
      bis[1-(4-phenylphenyl)-2-hydroxyimino-2-(4-chloroaniline)-1-ethylidene]- 1,3
      propanediamine), I4 were developed. Effects of the species and ratios of
      ionophore, plasticizer, PVC and lipophilic additive on the potentiometric
      response of electrodes were investigated in order to determine the electrode
      specifications. Overall results revealed that the optimum membrane composition
      was: 4% ionophore, 64% plasticizer (o-NPOE), 31% PVC, and 1% lipophilic additive
      (NaTPB). Obtained results showed that the electrodes have detection limit of
      1.76*10(-6), 1.68*10(-6), 2.35*10(-6) and 2.44*10(-6) and have linear responses
      of 34.2, 33.4, 35.9 and 37.6 mV/pHg(2+) for a wide concentration range of Hg(II)
      ions. According to durability studies, the electrodes can be used for
      approximately 1 month without any considerable divergence in potential values.
      Analytical applications of the electrodes were performed and it was found that
      developed electrodes can successfully be used as indicator electrodes for the
      potentiometric titration of Hg(II) ion with EDTA solution.

PMID- 25585283
TI  - Easy solid-phase synthesis of pH-insensitive heterogeneous CNTs/FeS Fenton-like
      catalyst for the removal of antibiotics from aqueous solution.
AB  - We report a facile solid method to synthesize efficient carbon-based Fenton-like
      catalyst (CNTs/FeS) using as-prepared carbon nanotubes (APCNTs), which makes full
      use of the iron nanoparticles in APCNTs without needless purification.
      Furthermore, the CNTs/FeS was characterized by transmission electron microscopy
      (TEM), X-ray diffraction (XRD), thermogravimetric (TG) and other analysis
      techniques, and then the CNTs/FeS was used as a Fenton-like catalyst for removing
      ciprofloxacin from aqueous solution. Response Surface Methodology (RSM) was
      applied to find the effect of the reaction parameter and the optimum operating
      condition. Results shows the catalytic reaction had better suitability than
      previous studies in a wide range of pH values (pH 3-8) and the Fenton-like
      catalyst CNTs/FeS exhibits good catalytic activity for removing of antibiotic,
      which be attributed to the synergistic effect of adsorption-advanced oxidation
      and significantly improves efficiency of advanced oxidation. More importantly,
      the CNTs/FeS catalyst exhibit good regeneration performance and retains a high
      catalytic capacity (>75%) even after four reaction cycles. The catalytic
      mechanism were also studied further, the removal mechanism of ciprofloxacin by a
      CNTs/FeS heterogeneous Fenton-like process primarily involves three removal
      pathways occurring simultaneously: (a) adsorption removal by CNTs, (b) Fenton
      like degradation catalyzed by FeS, (c) catalytic degradation by CNTs catalyst.
      And these actions also have synergistic effects for ciprofloxacin removal. 

PMID- 25585284
TI  - Super-hydrophobic surfaces of SiO2-coated SiC nanowires: fabrication, mechanism
      and ultraviolet-durable super-hydrophobicity.
AB  - The interest in highly water-repellent surfaces of SiO2-coated SiC nanowires has
      grown in recent years due to the desire for self-cleaning and anticorrosive
      surfaces. It is imperative that a simple chemical treatment with
      fluoroalkylsilane (FAS, CF3(CF2)7CH2CH2Si(OC2H5)3) in ethanol solution at room
      temperature resulted in super-hydrophobic surfaces of SiO2-coated SiC nanowires.
      The static water contact angle of SiO2-coated SiC nanowires surfaces was changed
      from 0 degrees  to 153 degrees  and the morphology, microstructure and crystal
      phase of the products were almost no transformation before and after super
      hydrophobic treatment. Moreover, a mechanism was expounded reasonably, which
      could elucidate the reasons for their super-hydrophobic behavior. It is important
      that the super-hydrophobic surfaces of SiO2-coated SiC nanowires possessed
      ultraviolet-durable (UV-durable) super-hydrophobicity. 

PMID- 25585285
TI  - Azide-functionalized hollow silica nanospheres for removal of antibiotics.
AB  - Antibiotics, which are hardly removed from polluted water by conventional water
      treatment technologies, adsorption has been deemed as one of the efficient and
      promising method to resolve the problems of antibiotics pollution. Herein, we
      reported a synthesis of filtration separable hollow nanostructured silicas (HNSs)
      with efficient click functionalization property for antibiotics adsorption. The
      clickable HNSs were synthesized by the co-condensation and assembling of
      tetramethoxysilane (TMOS) and 3-azidopropyltrimethoxysilane (AzPTMS) around F127
      single micelle template. Alkynyl compounds such as phenylacetylene (Ph),
      propargyl alcohol (PA), 1-heptyne (Hep), and 2-butyne-1,4-diol (BD) have been
      linked to the materials through click reaction with high efficiency. Antibiotic
      adsorption results reveal that functional groups play an important role in
      adsorption properties of adsorbents and phenyl was found to be the optimal
      functional group due to the pi-pi stacking effect. Excellent adsorption capacity
      and recyclability indicate that the clickable hollow nanostructured silicas
      exhibit potential application for antibiotics removal. 

PMID- 25585286
TI  - Relationship between surface hydroxyl groups and liquid-phase photocatalytic
      activity of titanium dioxide.
AB  - Both theories and experiments show that surface hydroxyl radicals (OH) are the
      most important intermediate species in the photocatalytic process. As a source of
      OH, surface hydroxyl (OH) groups play an important role in its generation. In
      this paper, the OH groups were divided into surface acidic hydroxyl (OH(a)) and
      surface basic hydroxyl (OH(b)) groups. From the detection by a method of surface
      acid-base, ion-exchange reactions, the total surface density of OH groups was
      about 9.58*10(-5) mol m(-2). The results measured by Fourier transform infrared
      spectroscopy, (1)H magnetic-angle spinning NMR and electron spin resonance
      techniques demonstrated that the role of OH(a) groups was greater than that of
      OH(b) groups on the generation of OH radicals. By degradation of methyl orange,
      rhodamine B and p-chlorophenol, the photocatalytic activities of the catalysts
      were directly influenced by the amount of OH groups.

PMID- 25585288
TI  - Designed synthesis of a novel BiVO4-Cu2O-TiO2 as an efficient visible-light
      responding photocatalyst.
AB  - A novel visible-light-responding BiVO4-Cu2O-TiO2 ternary heterostructure
      composite was successfully fabricated via the preparation of BiVO4-TiO2 followed
      by coupling with Cu2O through facile wet chemistry methods based on the strategy
      of energy gap engineering. The as-fabricated composite was characterized by X-ray
      powder diffraction, scanning electron microscopy, transmission electron
      microscopy, high-resolution transmission electron microscopy, UV-vis diffuse
      reflectance spectroscopy and X-ray photoelectron spectroscopy. Benefited from the
      rational design and construction, BiVO4-Cu2O-TiO2 exhibits a significantly
      enhanced photocatalytic activity for the degradation of rhodamine B (RhB) under
      the visible-light irradiation as compared with Cu2O and Cu2O-TiO2. Specifically,
      under the irradiation with an ordinary 9 W energy-saving fluorescent lamp for 8h,
      the photocatalytic degradation ratio of RhB for 5 wt%BiVO4-40 wt%Cu2O-TiO2
      reaches 97.8%. The enhanced photocatalytic activity of BiVO4-Cu2O-TiO2 can be
      ascribed to the matched band edge positions of BiVO4, Cu2O and TiO2, the
      heterojunction formations among them as well as the lower charge transfer
      resistance, favoring the separation of the photo-generated electron-hole pairs. A
      possible mechanism of the visible-light photocatalytic degradation of RhB is also
      proposed.

PMID- 25585287
TI  - A colloidal pseudocapacitor: direct use of Fe(NO3)3 in electrode can lead to a
      high performance alkaline supercapacitor system.
AB  - An electrochemical system including functioned Fe(NO3)3 and alkaline electrolyte
      is constructed to study the charge storage mechanism upon both thermodynamic
      calculations and electrochemical measurements. The thermodynamic calculation
      results demonstrate that increasing KOH concentration of alkaline electrolyte can
      enhance electrolyte activity but decrease the peak potential, which agrees well
      with that of electrochemical measurement. The present results indicate that the
      proposed pseudocapacitive redox reactions are between Fe(3+) and Fe(2+) in our
      salt electrode of Fe(NO3)3 system, in which the solid Fe(3+) in FeOOH colloids
      serves as the active anode component and free Fe(3+) on the colloidal electrodes
      serves as the cathode component. The active central ions of Fe(3+) in
      Fe(NO3)3?9H2O can be fixed on the electrodes by the surrounding ligands (OH(-)
      and NO3(-)) and can be in-situ transformed into colloidal Fe4NO3(OH)11 and
      goethite (alpha-FeOOH). Electrochemical results indicate that the current
      proposed colloidal pseudocapacitor system warrants the high-efficiency
      utilization of electroactive central Fe(3+) ions, showing high energy density of
      58.4 Wh/kg at the power density of 8.4 kW/kg as an anode material. Meanwhile, our
      designed pseudocapacitor system can function well as a supercapacitor cathode.
      This colloidal pseudocapacitor system can offer a facile and efficient route for
      the design of advanced supercapacitors.

PMID- 25585289
TI  - Robust antifogging antireflective coatings on polymer substrates by hydrochloric
      acid vapor treatment.
AB  - Antireflective coatings on polymer substrates have received significant attention
      for their potential applications. In this paper, robust microporous antifogging
      antireflective coatings on polymer substrates were prepared from acid-catalyzed
      silica sol followed by hydrochloric acid vapor solidification at mild temperature
      below glass transition temperatures of common polymers. The coatings passed 3H
      pencil hardness test, sand flow test and water-drop test. They had excellent
      antireflective and antifogging properties. The maximum transmittance of coatings
      on PMMA substrates reached 100.0% (the maximum transmittance wavelength could be
      regulated) and average transmittance reached 99.0% in 400-800 nm. The advantage
      and mechanism of hydrochloric acid vapor solidification and mechanical strength
      enhancement of coatings are discussed in contrast to ammonia vapor treatment and
      air vapor treatment. The hydrochloric acid vapor treatment results in a dense
      integrated microporous film structure. Optical properties were characterized by a
      UV-Vis spectrophotometer. Surface wettability was studied by a contact
      angle/interface system. Surface morphologies and structures of coatings were
      examined by scanning electron microscopy (SEM), transmission electron microscopy
      (TEM) and atom force microscopy (AFM).

PMID- 25585290
TI  - Mechanism of kaolinite sheets curling via the intercalation and delamination
      process.
AB  - Kaolinite naturally occurs in the plate form for the interlayer hydrogen bond and
      the distortion and adaption of tetrahedron and octahedron. But kaolinite sheets
      can be exfoliated to nanoscrolls artificially in laboratory through multiple-step
      displacement intercalation. The driving force for kaolinite sheet to be curled
      nanoscroll originates from the size discrepancy of Si-O tetrahedron and Al-O
      octahedron. The displacement intercalation promoted the platy kaolinite sheets
      spontaneously to be scrolled by eliminating the interlayer hydrogen bond and
      atomic interaction. Kaolinite nanoscrolls are hollow tubes with outer face of
      tetrahedral sheet and inner face of octahedral sheet. Based on the theoretical
      calculation it is firstly reported that the minimum interior diameter for a
      single kaolinite sheet to be scrolled is about 9.08 nm, and the optimal 24.30 nm,
      the maximum 100 nm, which is verified by the observation of scanning electron
      microscope and transmission electron microscope. The different adaption types and
      discrepancy degree between tetrahedron and octahedron generate various curling
      forces in different directions. The nanoscroll axes prefer the directions as
      [100], [11-0], [110], [31-0], and the relative curling force are as follows, [31
      0]>[100]=[11-0]>[110].

PMID- 25585291
TI  - Liquid infused porous surfaces for mineral fouling mitigation.
AB  - Prevention of mineral fouling, known as scale, is a long-standing problem in a
      wide variety of industrial applications, such as oil production, water treatment,
      and many others. The build-up of inorganic scale such as calcium carbonate on
      surfaces and facilities is undesirable as it can result in safety risks and
      associated flow assurance issues. To date the overwhelming amount of research has
      mainly focused on chemical inhibition of scale bulk precipitation and little
      attention has been paid to deposition onto surfaces. The development of novel
      more environmentally-friendly strategies to control mineral fouling will most
      probably necessitate a multifunctional approach including surface engineering. In
      this study, we demonstrate that liquid infused porous surfaces provide an
      appealing strategy for surface modification to reduce mineral scale deposition.
      Microporous polypyrrole (PPy) coatings were fabricated onto stainless steel
      substrates by electrodeposition in potentiostatic mode. Subsequent infusion of
      low surface energy lubricants (fluorinated oil Fluorinert FC-70 and ionic liquid
      1-Butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMIm)) into the
      porous coatings results in liquid-repellent slippery surfaces. To assess their
      ability to reduce surface scaling the coatings were subjected to a calcium
      carbonate scaling environment and the scale on the surface was quantified using
      Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES). PPy surfaces
      infused with BMIm (and Fluorinert to a lesser extent) exhibit remarkable
      antifouling properties with the calcium carbonate deposition reduced by 18 times
      in comparison to untreated stainless steel. These scaling tests suggest a
      correlation between the stability of the liquid infused surfaces in artificial
      brines and fouling reduction efficiency. The current work shows the great
      potential of such novel coatings for the management of mineral scale fouling. 

PMID- 25585292
TI  - A hydrothermal peroxo method for preparation of highly crystalline silica-titania
      photocatalysts.
AB  - A new completely inorganic method of preparation of silica-titania photocatalyst
      has been described. It has been established that the addition of silica promotes
      crystallinity of TiO2 anatase phase. Relative crystallinity and TiO2 crystal size
      in the silica-titania particles increase with the silica content until SiO2/TiO2
      molar ratio of 0.9, but at higher molar ratios they start to decrease. The single
      source precursor containing peroxo titanic (PTA) and silicic acids has been
      proved to be responsible for high crystallinity of TiO2 encapsulated into
      amorphous silica. It has been proposed that peroxo groups enhance rapid formation
      of crystalline titania seeds, while silica controls their growth. It has been
      concluded from the TEM that the most morphologically uniform anatase crystallites
      covered with SiO2 particles are prepared at SiO2/TiO2 molar ratio of 0.4. This
      sample, according to (29)Si NMR, also shows the high content of hydroxylated
      silica Q(3) and Q(2) groups, and it is the most photocatalytically active in UV
      assisted decomposition of methylene blue among the tested materials. It has been
      determined that the increase in the amount of the condensed Q(4) silica in the
      mixed oxides leads to the decrease in photocatalytic performance of the material,
      despite its better crystallinity. High crystallinity, low degree of incorporation
      of Ti atoms in SiO2 in the mixed oxide and adsorption of methylene blue in the
      vicinity of photoactive sites on the hydroxylated silica have been considered as
      the main factors determining the high degradation degree of methylene blue in the
      presence of silica-titania. 

PMID- 25585293
TI  - Microwave synthesis of ZnO@mSiO2 for detailed antifungal mode of action study:
      understanding the insights into oxidative stress.
AB  - A simple chemical method has been devised for deliberate incorporation of zinc
      oxide nanoparticles (ZNPs) within mesoporous nanosilica (mSiO2) matrix to yield
      zinc oxide nanoparticles embedded in mesoporous nanosilica (ZnO@mSiO2). ZnO@mSiO2
      inhibited the growth of four strains of fungi in a dose dependant manner. A
      series of biochemical assays revealed generation of oxidative stress from
      ZnO@mSiO2 for such biocidal response. We proposed transient superoxide and its
      subsequent conversion to H2O2 played a pivotal role behind such biocidal response
      as revealed from our systematic evaluation. This resulted morphological
      alteration of fungi through increase in number of facets, in correlation we found
      up-regulation in oxidative stress related genes. Bioavailability within the
      fungal sample was confirmed from microscopic, spectroscopic, biophysical
      techniques. Protein carbonylation of fungal species was the chemical outcome of
      such above mentioned stress and quantified by high performance liquid
      chromatography (HPLC) via subsequent hydrazone derivatization. Several in vitro
      and in vivo evaluations revealed the biocompatibility of ZnO@mSiO2. Altogether
      this report claims a new biocidal agent with a detailed mode of action focusing
      on the origin and quantification of oxidative stress through biophysical and
      biochemical techniques for the first time for real time applications. 

PMID- 25585295
TI  - Recoverable plasticity in penta-twinned metallic nanowires governed by
      dislocation nucleation and retraction.
AB  - There has been relatively little study on time-dependent mechanical properties of
      nanowires, in spite of their importance for the design, fabrication and operation
      of nanoscale devices. Here we report a dislocation-mediated, time-dependent and
      fully reversible plastic behaviour in penta-twinned silver nanowires. In situ
      tensile experiments inside scanning and transmission electron microscopes show
      that penta-twinned silver nanowires undergo stress relaxation on loading and
      complete plastic strain recovery on unloading, while the same experiments on
      single-crystalline silver nanowires do not exhibit such a behaviour. Molecular
      dynamics simulations reveal that the observed behaviour in penta-twinned
      nanowires originates from the surface nucleation, propagation and retraction of
      partial dislocations. More specifically, vacancies reduce dislocation nucleation
      barrier, facilitating stress relaxation, while the twin boundaries and their
      intrinsic stress field promote retraction of partial dislocations, resulting in
      full strain recovery. 

PMID- 25585294
TI  - Under-reporting of dietary energy intake in five populations of the African
      diaspora.
AB  - Studies on the role of diet in the development of chronic diseases often rely on
      self-report surveys of dietary intake. Unfortunately, many validity studies have
      demonstrated that self-reported dietary intake is subject to systematic under
      reporting, although the vast majority of such studies have been conducted in
      industrialised countries. The aim of the present study was to investigate whether
      or not systematic reporting error exists among the individuals of African
      ancestry (n 324) in five countries distributed across the Human Development Index
      (HDI) scale, a UN statistic devised to rank countries on non-income factors plus
      economic indicators. Using two 24 h dietary recalls to assess energy intake and
      the doubly labelled water method to assess total energy expenditure, we
      calculated the difference between these two values ((self-report -
      expenditure/expenditure) * 100) to identify under-reporting of habitual energy
      intake in selected communities in Ghana, South Africa, Seychelles, Jamaica and
      the USA. Under-reporting of habitual energy intake was observed in all the five
      countries. The South African cohort exhibited the highest mean under-reporting ( 
      52.1% of energy) compared with the cohorts of Ghana ( - 22.5%), Jamaica ( -
      17.9%), Seychelles ( - 25.0%) and the USA ( - 18.5%). BMI was the most consistent
      predictor of under-reporting compared with other predictors. In conclusion, there
      is substantial under-reporting of dietary energy intake in populations across the
      whole range of the HDI, and this systematic reporting error increases according
      to the BMI of an individual.

PMID- 25585296
TI  - A Rosetta Stone for nature's benefits to people.
AB  - After a long incubation period, the Intergovernmental Platform on Biodiversity
      and Ecosystem Services (IPBES) is now underway. Underpinning all its activities
      is the IPBES Conceptual Framework (CF), a simplified model of the interactions
      between nature and people. Drawing on the legacy of previous large-scale
      environmental assessments, the CF goes further in explicitly embracing different
      disciplines and knowledge systems (including indigenous and local knowledge) in
      the co-construction of assessments of the state of the world's biodiversity and
      the benefits it provides to humans. The CF can be thought of as a kind of
      "Rosetta Stone" that highlights commonalities between diverse value sets and
      seeks to facilitate crossdisciplinary and crosscultural understanding. We argue
      that the CF will contribute to the increasing trend towards interdisciplinarity
      in understanding and managing the environment. Rather than displacing
      disciplinary science, however, we believe that the CF will provide new contexts
      of discovery and policy applications for it. 

PMID- 25585297
TI  - High Reproducibility of ELISPOT Counts from Nine Different Laboratories.
AB  - The primary goal of immune monitoring with ELISPOT is to measure the number of T
      cells, specific for any antigen, accurately and reproducibly between different
      laboratories. In ELISPOT assays, antigen-specific T cells secrete cytokines,
      forming spots of different sizes on a membrane with variable background
      intensities. Due to the subjective nature of judging maximal and minimal spot
      sizes, different investigators come up with different numbers. This study aims to
      determine whether statistics-based, automated size-gating can harmonize the
      number of spot counts calculated between different laboratories. We plated PBMC
      at four different concentrations, 24 replicates each, in an IFN-gamma ELISPOT
      assay with HCMV pp65 antigen. The ELISPOT plate, and an image file of the plate
      was counted in nine different laboratories using ImmunoSpot(r) Analyzers by (A)
      Basic CountTM relying on subjective counting parameters set by the respective
      investigators and (B) SmartCountTM, an automated counting protocol by the
      ImmunoSpot(r) Software that uses statistics-based spot size auto-gating with spot
      intensity auto-thresholding. The average coefficient of variation (CV) for the
      mean values between independent laboratories was 26.7% when counting with Basic
      CountTM, and 6.7% when counting with SmartCountTM. Our data indicates that
      SmartCountTM allows harmonization of counting ELISPOT results between different
      laboratories and investigators. 

PMID- 25585298
TI  - Serial Measurements of Apoptotic Cell Numbers Provide Better Acceptance Criterion
      for PBMC Quality than a Single Measurement Prior to the T Cell Assay.
AB  - As soon as Peripheral Blood Mononuclear Cells (PBMC) are isolated from whole
      blood, some cells begin dying. The rate of apoptotic cell death is increased when
      PBMC are shipped, cryopreserved, or stored under suboptimal conditions. Apoptotic
      cells secrete cytokines that suppress inflammation while promoting phagocytosis.
      Increased numbers of apoptotic cells in PBMC may modulate T cell functions in
      antigen-triggered T cell assays. We assessed the effect of apoptotic bystander
      cells on a T cell ELISPOT assay by selectively inducing B cell apoptosis using
      alpha-CD20 mAbs. The presence of large numbers of apoptotic B cells did not
      affect T cell functionality. In contrast, when PBMC were stored under unfavorable
      conditions, leading to damage and apoptosis in the T cells as well as bystander
      cells, T cell functionality was greatly impaired. We observed that measuring the
      number of apoptotic cells before plating the PBMC into an ELISPOT assay did not
      reflect the extent of PBMC injury, but measuring apoptotic cell frequencies at
      the end of the assay did. Our data suggest that measuring the numbers of
      apoptotic cells prior to and post T cell assays may provide more stringent PBMC
      quality acceptance criteria than measurements done only prior to the start of the
      assay. 

PMID- 25585299
TI  - Brief report: HIV-1 transmissions during asymptomatic infection: exploring the
      impact of changes in HIV-1 viral load due to coinfections.
AB  - High HIV-1 plasma viral loads (PVLs) in sub-Saharan Africa, partly because of
      high rates of coinfection, may have been one of the drivers of the "explosive"
      epidemics seen in that region. Using a previously published framework of
      infectiousness and survival, we estimate the excess onward HIV-1 transmission
      events (secondary infections) resulting from coinfection-induced changes in PVL
      during asymptomatic HIV-1 infection. For every 100 HIV-infected people, each
      suffering 1 episode of tuberculosis infection, there are 4.9 (2.7th-97.5th
      percentile: 0.2-21.5) excess onward HIV-1 transmission events attributable to
      this coinfection. Other estimates are malaria 0.4 (0.0-2.0), soil-transmitted
      helminths 3.1 (0.1-14.9), schistosomiasis 8.5 (0.2-38.6), filariasis 13.3 (0.3
      89.2), syphilis 0.1 (0.0-1.6), herpes simplex virus 4.0 (0.0-24.2), and gonorrhea
      2.1 (0.1-8.0) transmissions. If these higher PVLs confer a shorter life
      expectancy and higher infectiousness, then their impact on transmission is, in
      general, reduced. For most HIV-1 coinfections, the duration of a single infection
      is too short and/or the associated PVL elevation is too modest to contribute
      substantially to onward HIV-1 transmission. 

PMID- 25585300
TI  - Brief report: Validation of a quantitative HIV risk prediction tool using a
      national HIV testing cohort.
AB  - Routine screening is recommended for HIV detection. HIV risk estimation remains
      important. Our goal was to validate the Denver HIV Risk Score using a national
      cohort from the Centers for Disease Control and Prevention. Patients of 13 years
      and older were included, 4,830,941 HIV tests were performed, and 0.6% newly
      diagnosed infections were identified. Of all visits, 9% were very low risk (HIV
      prevalence = 0.20%), 27% low risk (HIV prevalence = 0.17%), 41% moderate risk
      (HIV prevalence = 0.39%), 17% high risk (HIV prevalence = 1.19%), and 6% very
      high risk (HIV prevalence = 3.57%). The Denver HIV Risk Score accurately
      categorized patients into different HIV risk groups.

PMID- 25585301
TI  - Risk factors and mortality associated with resistance to first-line
      antiretroviral therapy: multicentric cross-sectional and longitudinal analyses.
AB  - BACKGROUND: Understanding the factors associated with HIV drug resistance
      development and subsequent mortality is important to improve clinical patient
      management. METHODS: Analysis of individual electronic health records from 4 HIV
      programs in Malawi, Kenya, Uganda, and Cambodia, linked to data from 5 cross
      sectional virological studies conducted among patients receiving first-line
      antiretroviral therapy (ART) for >=6 months. Adjusted logistic and Cox-regression
      models were used to identify risk factors for drug resistance and subsequent
      mortality. RESULTS: A total of 2257 patients (62% women) were included. At ART
      initiation, median CD4 cell count was 100 cells per microliter (interquartile
      range, 40-165). A median of 25.1 months after therapy start, 18% of patients had
      >=400 and 12.4% >=1000 HIV RNA copies per milliliter. Of 180 patients with drug
      resistance data, 83.9% had major resistance(s) to nucleoside or nonnucleoside
      reverse transcriptase inhibitors, and 74.4% dual resistance. Resistance to
      nevirapine, lamivudine, and efavirenz was common, and 6% had etravirine cross
      resistance. Risk factors for resistance were young age (<35 years), low CD4 cell
      count (<200 cells/MUL), and poor treatment adherence. During 4978 person-years of
      follow-up after virological testing (median = 31.8 months), 57 deaths occurred
      [rate = 1.14/100 person-years; 95% confidence interval (CI): 0.88 to 1.48].
      Mortality was higher in patients with resistance (hazard ratio = 2.08; 95% CI:
      1.07 to 4.07 vs. <400 copies/mL), and older age (hazard ratio = 2.41; 95% CI:
      1.24 to 4.71 for >=43 vs. <=34 years), and lower in those receiving ART for >30
      months. CONCLUSIONS: Our findings underline the importance of optimal treatment
      adherence and adequate virological response monitoring and emphasize the need for
      resistance surveillance initiatives even in HIV programs achieving high
      virological suppression rates.

PMID- 25585302
TI  - Implementation and operational research: the impact of option B+ on the antenatal
      PMTCT cascade in Lilongwe, Malawi.
AB  - OBJECTIVE: In 2011, Malawi implemented Option B+ (B+), lifelong antiretroviral
      therapy (ART) for pregnant and breastfeeding women. We aimed to describe changes
      in service uptake and outcomes along the antenatal prevention of mother-to-child
      transmission (PMTCT) cascade post-B+ implementation. DESIGN: Pre/post study using
      routinely collected program data from 2 large Lilongwe-based health centers.
      METHODS: We compared the testing of HIV-infected pregnant women at antenatal
      care, enrollment into PMTCT services, receipt of ART, and 6-month ART outcomes
      pre-B+ (October 2009-March 2011) and post-B+ (October 2011-March 2013). RESULTS:
      A total of 13,926 (pre) and 14,532 (post) women presented to antenatal care. Post
      B+, a smaller proportion were HIV-tested (99.3% vs. 87.7% post-B+; P < 0.0001).
      There were 1654 (pre) and 1535 (post) HIV-infected women identified, with a
      larger proportion already known to be HIV-infected (18.1% vs. 41.2% post-B+; P <
      0.0001) and on ART post-B+ (18.7% vs. 30.2% post-B+; P < 0.0001). A significantly
      greater proportion enrolled into the PMTCT program (68.3% vs. 92.6% post-B+; P <
      0.0001) and was retained through delivery post-B+ (51.1% vs. 65% post-B+; P <
      0.0001). Among those not on ART at enrollment, there was no change in the
      proportion newly initiating ART/antiretrovirals (79% vs. 81.9% post-B+; P =
      0.11), although median days to initiation of ART decreased [48 days (19, 130) vs.
      0 days (0, 15.5) post-B+; P < 0.0001]. Among those newly initiating ART, a
      smaller proportion was alive on ART 6 months after initiation (89.3% vs. 78.8%
      post-B+; P = 0.0004). CONCLUSIONS: Although several improvements in PMTCT program
      performance were noted with implementation of B+, challenges remain at several
      critical steps along the cascade requiring innovative solutions to ensure an AIDS
      free generation.

PMID- 25585303
TI  - Pediatric Optic Nerve Meningioma: Diagnostic and Therapeutic Challenges.
AB  - A 13-year-old female presented with left unilateral proptosis, blurry vision, and
      diplopia. Clinical examination showed left sided visual acuity of 20/50, limited
      extraocular movement, 5-mm proptosis, and optic disc edema. CT and MRI displayed
      a large, intraconal, well-demarcated soft tissue mass with inferotemporal
      displacement of the optic nerve. The imaging appearance was unusual and diagnosis
      remained uncertain. Histopathologic analysis of the biopsy specimen confirmed the
      diagnosis of atypical syncytial meningioma. The tumor cells were positive for
      both androgen and progesterone receptors and the Ki67 stain was positive
      (proliferation index of 8%). The patient was treated with proton beam radiation
      therapy (total dose 50.4 GyE) that suppressed tumor growth and has preserved
      visual acuity to date (20/40). Differential diagnosis and approaches to therapy
      are explored.

PMID- 25585304
TI  - Predicting the Development of Orbitopathy in Graves Thyroidopathy Patients: The
      Potential Role of TSI Testing.
AB  - OBJECTIVE: To determine whether thyroid-stimulating immunoglobulin (TSI) testing
      can predict the risk of development of Graves orbitopathy in newly diagnosed
      Graves thyroidopathy patients. DESIGN: Retrospective cohort, from 2008 to 2013.
      SETTING: The Thyroid Referral Center at California Pacific Medical Center.
      PARTICIPANTS: A retrospective cohort of newly diagnosed Graves thyroidopathy
      patients from the California Pacific Medical Center Thyroid Referral Center.
      Patients were included if they had TSIs drawn at or near the time of diagnosis of
      Graves thyroidopathy. Patients were excluded from the study if they had a long
      standing diagnosis of Graves thyroidopathy, orbitopathy at time of diagnosis, no
      TSIs drawn, or follow up of less than 6 months. MAIN OUTCOME MEASURES: Patients
      were followed for the development of orbitopathy as determined by their
      endocrinologists. Results were adjusted for family history, smoking status, age,
      radioiodine ablation treatment, and race. RESULTS: Thirty-three patients met
      inclusion criteria out of a screened population of 506 patients. Eight out of 33
      patients (24%) developed orbitopathy. The mean time from diagnosis of Graves'
      thyroidopathy to development of orbitopathy was 11.6 months (median: 7.5 months,
      range: 1 to 20 months). The mean initial TSI value was 421.3 in those that
      developed orbitopathy compared to 245.9 in those who had at least 6 months of
      documented follow-up and did not develop orbitopathy (p = 0.04). Those in the top
      tercile of initial TSI values were 14 times as likely to develop orbitopathy
      (relative risk (RR) = 14.0, p = 0.02; multivariate adjusted RR = 13.08, p =
      0.03). Family history, smoking status, age, radioiodine ablation, thyroid
      stimulating hormone, and race were not statistically significant predictors.
      CONCLUSIONS: TSI level greater than 400 at time of presentation of Graves
      thyroidopathy may be a useful predictor of risk for development of orbitopathy.
      This information will help to identify patients likely to benefit from early
      referral to an ophthalmologist for possible preemptive therapy to prevent the
      development of orbitopathy. Prospective cohort studies are needed to definitively
      establish the metrics for TSI as a predictor of orbitopathy.

PMID- 25585305
TI  - Mitochondrial Neurogastrointestinal Encephalomyopathy Treated with Stem Cell
      Transplantation: A Case Report and Review of Literature.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal
      recessive disorder. The mutation in the ECGF1 gene causes severe deficiency of
      thymidine phosphorylase (TP), which in turn increases thymidine and deoxyuridine
      in the blood, serum, and tissue. The toxic levels of these products cause
      malfunction of the mitochondrial respiratory chain and mitochondrial DNA.
      Commonly, patients become symptomatic between 15 and 20 years of age (range 5
      months to 35 years). The most commonly affected systems are gastrointestinal,
      followed by ocular, and nervous system. The disease is often fatal; high
      mortality rate is reported between 20 and 40 years of age. Treatment modalities
      that can increase thymidine phosphorylase activity and decrease thymidine and
      deoxy-uridine have shown symptomatic improvements in patients with MNGIE.
      Platelet transfusion, hemodialysis, peritoneal dialysis or allogeneic
      hematopoietic stem cell transplantation (HSCT) have been tried. The survival and
      long-term benefits of these measures are still not clear. Engrafted patients
      after stem cell transplantation have showed improvements in serum thymidine and
      deoxyuridine. We are reporting a case of MNGIE from Saudi Arabia, who underwent
      allogeneic hematopoietic stem cell transplantation. No MNGIE case has been
      previously reported from Saudi Arabia or the Gulf Arab countries. From the
      available literature, so far only 11 patients with MNGIE have undergone stem cell
      transplantation.

PMID- 25585306
TI  - Vulvar extrauterine endometrial stromal sarcoma: A case report and literature
      review.
AB  - Endometrial stromal sarcoma (ESS) is an extremely rare neoplasm accounting for
      only 0.2% of all uterine malignancies and for 15-26% of primary uterine sarcomas.
      The annual incidence of ESS is 1-2 per million women. Herein, to the best of our
      knowledge, we present the first reported case of ESS of the vulva in a 50-year
      old female presenting with per vaginal spotting over a period of three months.
      Her past surgical history included a subtotal hysterectomy and left salpingo
      oophorectomy for uterine fibroids ten years previously. On examination, a 3.5*3*2
      cm cystic mass was found in the right labia majora. The mass was excised and the
      diagnosis of endometrial stromal sarcoma was made. Subsequent metastatic workup
      was negative and the patient was started on megestrol acetate. She has remained
      disease free with no signs or symptoms of recurrent or advanced disease for 28
      months.

PMID- 25585309
TI  - Fogbound shores, Antarctica: Leland Curtis.

PMID- 25585310
TI  - ASCO calls for Medicaid reform to improve cancer care for beneficiaries.

PMID- 25585311
TI  - States are the key to both strengthening and replacing the Affordable Care Act.

PMID- 25585318
TI  - Exceptional opportunities in medical science: a view from the National Institutes
      of Health.

PMID- 25585319
TI  - Supporting biomedical research: meeting challenges and opportunities at HHMI.

PMID- 25585320
TI  - Nanotechnology.

PMID- 25585321
TI  - A piece of my mind. Take a look at me now.

PMID- 25585322
TI  - Improving cardiovascular health in a rural population: can other communities do
      the same?

PMID- 25585323
TI  - Race, ethnicity, and the diagnosis of breast cancer.

PMID- 25585324
TI  - Restore the US lead in biomedical research.

PMID- 25585325
TI  - Scientific discovery and the future of medicine.

PMID- 25585326
TI  - Community-wide cardiovascular disease prevention programs and health outcomes in
      a rural county, 1970-2010.
AB  - IMPORTANCE: Few comprehensive cardiovascular risk reduction programs,
      particularly those in rural, low-income communities, have sustained community
      wide interventions for more than 10 years and demonstrated the effect of risk
      factor improvements on reductions in morbidity and mortality. OBJECTIVE: To
      document health outcomes associated with an integrated, comprehensive
      cardiovascular risk reduction program in Franklin County, Maine, a low-income
      rural community. DESIGN, SETTING, AND PARTICIPANTS: Forty-year observational
      study involving residents of Franklin County, Maine, a rural, low-income
      population of 22,444 in 1970, that used the preceding decade as a baseline and
      compared Franklin County with other Maine counties and state averages.
      INTERVENTIONS: Community-wide programs targeting hypertension, cholesterol, and
      smoking, as well as diet and physical activity, sponsored by multiple community
      organizations, including the local hospital and clinicians. MAIN OUTCOMES AND
      MEASURES: Resident participation; hypertension and hyperlipidemia detection,
      treatment, and control; smoking quit rates; hospitalization rates from 1994
      through 2006, adjusted for median household income; and mortality rates from 1970
      through 2010, adjusted for household income and age. RESULTS: More than 150,000
      individual county resident contacts occurred over 40 years. Over time, as
      cardiovascular risk factor programs were added, relevant health indicators
      improved. Hypertension control had an absolute increase of 24.7% (95% CI, 21.6%
      27.7%) from 18.3% to 43.0%, from 1975 to 1978; later, elevated cholesterol
      control had an absolute increase of 28.5% (95% CI, 25.3%-31.6%) from 0.4% to
      28.9%, from 1986 to 2010. Smoking quit rates improved from 48.5% to 69.5%, better
      than state averages (observed - expected [O - E], 11.3%; 95% CI, 5.5%-17.7%; P <
      .001), 1996-2000; these differences later disappeared when Maine's overall quit
      rate increased. Franklin County hospitalizations per capita were less than
      expected for the measured period, 1994-2006 (O - E, -17 discharges/1000
      residents; 95% CI -20.1 to -13.9; P < .001). Franklin was the only Maine county
      with consistently lower adjusted mortality than predicted over the time periods
      1970-1989 and 1990-2010 (O - E, -60.4 deaths/100,000; 95% CI, -97.9 to -22.8; P <
      .001, and -41.6/100,000; 95% CI, -77.3 to -5.8; P = .005, respectively).
      CONCLUSIONS AND RELEVANCE: Sustained, community-wide programs targeting
      cardiovascular risk factors and behavior changes to improve a Maine county's
      population health were associated with reductions in hospitalization and
      mortality rates over 40 years, compared with the rest of the state. Further
      studies are needed to assess the generalizability of such programs to other US
      county populations, especially rural ones, and to other parts of the world.

PMID- 25585327
TI  - Association between asthma and risk of developing obstructive sleep apnea.
AB  - IMPORTANCE: Obstructive sleep apnea (OSA) is more common among patients with
      asthma; whether asthma is associated with the development of OSA is unknown.
      OBJECTIVE: To examine the prospective relationship of asthma with incident OSA.
      DESIGN, SETTING, AND PARTICIPANTS: Population-based prospective epidemiologic
      study (the Wisconsin Sleep Cohort Study) beginning in 1988. Adult participants
      were recruited from a random sample of Wisconsin state employees to attend
      overnight polysomnography studies at 4-year intervals. Asthma and covariate
      information were assessed during polysomnography studies through March 2013.
      Eligible participants were identified as free of OSA (apnea-hypopnea index [AHI]
      of <5 events/h and not treated) by 2 baseline polysomnography studies. There were
      1105 4-year follow-up intervals provided by 547 participants (52% women; mean
      [SD] baseline age, 50 [8] years). EXPOSURES: Questionnaire-assessed presence and
      duration of self-reported physician-diagnosed asthma. MAIN OUTCOMES AND MEASURES:
      The associations of presence and duration of asthma with 4-year incidences of
      both OSA (AHI of >=5 or positive airway pressure treatment) and OSA concomitant
      with habitual daytime sleepiness were estimated using repeated-measures Poisson
      regression, adjusting for confounders. RESULTS: Twenty-two of 81 participants
      (27% [95% CI, 17%-37%]) with asthma experienced incident OSA over their first
      observed 4-year follow-up interval compared with 75 of 466 participants (16% [95%
      CI, 13%-19%]) without asthma. Using all 4-year intervals, participants with
      asthma experienced 45 cases of incident OSA during 167 4-year intervals (27% [95%
      CI, 20%-34%]) and participants without asthma experienced 160 cases of incident
      OSA during 938 4-year intervals (17% [95% CI, 15%-19%]); the corresponding
      adjusted relative risk (RR) was 1.39 (95% CI, 1.06-1.82), controlling for sex,
      age, baseline and change in body mass index, and other factors. Asthma was also
      associated with new-onset OSA with habitual sleepiness (RR, 2.72 [95% CI, 1.26
      5.89], P = .045). Asthma duration was related to both incident OSA (RR, 1.07 per
      5-year increment in asthma duration [95% CI, 1.02-1.13], P = .01) and incident
      OSA with habitual sleepiness (RR, 1.18 [95% CI, 1.07-1.31], P = .02). CONCLUSIONS
      AND RELEVANCE: Asthma was associated with an increased risk of new-onset OSA.
      Studies investigating the mechanisms underlying this association and the value of
      periodic OSA evaluation in patients with asthma are warranted.

PMID- 25585328
TI  - Differences in breast cancer stage at diagnosis and cancer-specific survival by
      race and ethnicity in the United States.
AB  - IMPORTANCE: Women with early-stage breast cancers are expected to have excellent
      survival rates. It is important to identify factors that predict diagnosis of
      early-stage breast cancers. OBJECTIVE: To determine the proportion of breast
      cancers that were identified at an early stage (stage I) in different
      racial/ethnic groups and whether ethnic differences may be better explained by
      early detection or by intrinsic biological differences in tumor aggressiveness.
      DESIGN, SETTING, AND PARTICIPANTS: Observational study of women diagnosed with
      invasive breast cancer from 2004 to 2011 who were identified in the Surveillance,
      Epidemiology, and End Results (SEER) 18 registries database (N = 452,215). For
      each of 8 racial/ethnic groups, biological aggressiveness (triple-negative
      cancers, lymph node metastases, and distant metastases) of small-sized tumors of
      2.0 cm or less was estimated. The odds ratio (OR) for being diagnosed at stage I
      compared with a later stage and the hazard ratio (HR) for death from stage I
      breast cancer by racial/ethnic group were determined. The date of final follow-up
      was December 31, 2011. MAIN OUTCOMES AND MEASURES: Breast cancer stage at
      diagnosis and 7-year breast cancer-specific survival, adjusted for age at
      diagnosis, income, and estrogen receptor status. RESULTS: Of 373,563 women with
      invasive breast cancer, 268,675 (71.9%) were non-Hispanic white; 34,928 (9.4%),
      Hispanic white; 38,751 (10.4%), black; 25,211 (6.7%), Asian; and 5998 (1.6%),
      other ethnicities. Mean follow-up time was 40.6 months (median, 38 months).
      Compared with non-Hispanic white women diagnosed with stage I breast cancer
      (50.8%), Japanese women (56.1%) were more likely to be diagnosed (OR, 1.23 [95%
      CI, 1.15-1.31], P < .001) and black women (37.0%) were less likely to be
      diagnosed (OR, 0.65 [95% CI, 0.64-0.67], P < .001). Actuarial risk of death from
      stage I breast cancer at 7 years was higher among black women (6.2%) than non
      Hispanic white women (3.0%) (HR, 1.57 [95% CI, 1.40-1.75]; P < .001), and lower
      among South Asian women (1.7%) (HR, 0.48 [95% CI, 0.20-1.15]; P = .10). Black
      women were more likely to die of breast cancer with small-sized tumors (9.0%)
      than non-Hispanic white women (4.6%) (HR, 1.96 [95% CI, 1.82-2.12]; P < .001);
      the difference remained after adjustment for income and estrogen receptor status
      (HR, 1.56 [95% CI, 1.45-1.69]; P < .001). CONCLUSIONS AND RELEVANCE: Among US
      women diagnosed with invasive breast cancer, the likelihood of diagnosis at an
      early stage, and survival after stage I diagnosis, varied by race and ethnicity.
      Much of the difference could be statistically accounted for by intrinsic
      biological differences such as lymph node metastasis, distant metastasis, and
      triple-negative behavior of tumors.

PMID- 25585329
TI  - The anatomy of medical research: US and international comparisons.
AB  - IMPORTANCE: Medical research is a prerequisite of clinical advances, while health
      service research supports improved delivery, access, and cost. Few previous
      analyses have compared the United States with other developed countries.
      OBJECTIVES: To quantify total public and private investment and personnel
      (economic inputs) and to evaluate resulting patents, publications, drug and
      device approvals, and value created (economic outputs). EVIDENCE REVIEW: Publicly
      available data from 1994 to 2012 were compiled showing trends in US and
      international research funding, productivity, and disease burden by source and
      industry type. Patents and publications (1981-2011) were evaluated using citation
      rates and impact factors. FINDINGS: (1) Reduced science investment: Total US
      funding increased 6% per year (1994-2004), but rate of growth declined to 0.8%
      per year (2004-2012), reaching $117 billion (4.5%) of total health care
      expenditures. Private sources increased from 46% (1994) to 58% (2012). Industry
      reduced early-stage research, favoring medical devices, bioengineered drugs, and
      late-stage clinical trials, particularly for cancer and rare diseases. National
      Insitutes of Health allocations correlate imperfectly with disease burden, with
      cancer and HIV/AIDS receiving disproportionate support. (2) Underfunding of
      service innovation: Health services research receives $5.0 billion (0.3% of total
      health care expenditures) or only 1/20th of science funding. Private insurers
      ranked last (0.04% of revenue) and health systems 19th (0.1% of revenue) among 22
      industries in their investment in innovation. An increment of $8 billion to $15
      billion yearly would occur if service firms were to reach median research and
      development funding. (3) Globalization: US government research funding declined
      from 57% (2004) to 50% (2012) of the global total, as did that of US companies
      (50% to 41%), with the total US (public plus private) share of global research
      funding declining from 57% to 44%. Asia, particularly China, tripled investment
      from $2.6 billion (2004) to $9.7 billion (2012) preferentially for education and
      personnel. The US share of life science patents declined from 57% (1981) to 51%
      (2011), as did those considered most valuable, from 73% (1981) to 59% (2011).
      CONCLUSIONS AND RELEVANCE: New investment is required if the clinical value of
      past scientific discoveries and opportunities to improve care are to be fully
      realized. Sources could include repatriation of foreign capital, new innovation
      bonds, administrative savings, patent pools, and public-private risk sharing
      collaborations. Given international trends, the United States will relinquish its
      historical international lead in the next decade unless such measures are
      undertaken.

PMID- 25585330
TI  - Rates of psychiatrists' participation in health insurance networks.

PMID- 25585331
TI  - Screening for asymptomatic carotid artery stenosis.

PMID- 25585332
TI  - Lactate in sepsis.

PMID- 25585333
TI  - Variation in and factors associated with use of episiotomy.

PMID- 25585334
TI  - Decision-support guide and use of prenatal genetic testing.

PMID- 25585335
TI  - Decision-support guide and use of prenatal genetic testing.

PMID- 25585336
TI  - Decision-support guide and use of prenatal genetic testing--reply.

PMID- 25585337
TI  - Reporting of diabetes trends among Asian Americans, Native Hawaiians, and Pacific
      Islanders.

PMID- 25585338
TI  - Reporting of diabetes trends among Asian Americans, Native Hawaiians, and Pacific
      Islanders--reply.

PMID- 25585339
TI  - Direct-to-consumer screening companies.

PMID- 25585342
TI  - The medicine of the future.

PMID- 25585340
TI  - Direct-to-consumer screening companies--reply.

PMID- 25585343
TI  - JAMA patient page. Testing for carotid stenosis.

PMID- 25585344
TI  - Re: Does structured withdrawal of desmopressin improve relapse rates in patients
      with monosymptomatic enuresis?: M. I. Gokce, P. Hajiyev, E. Suer, Y. Kibar, M. S.
      Silay, S. Gurocak, H. S. Dogan, H. C. Irkilata, T. Oktar, B. Onal, E. Erdem, Y.
      C. Aygun, C. Balci, A. R. Arslan, C. Kaya, T. Soygur, S. Sarikaya, S. Tekgul and
      B. Burgu, J Urol 2014;192:530-534.

PMID- 25585345
TI  - O-GlcNAcylation of co-activator-associated arginine methyltransferase 1 regulates
      its protein substrate specificity.
AB  - Co-activator-associated arginine methyltransferase 1 (CARM1) asymmetrically di
      methylates proteins on arginine residues. CARM1 was previously known to be
      modified through O-linked-beta-N-acetylglucosaminidation (O-GlcNAcylation).
      However, the site(s) of O-GlcNAcylation were not mapped and the effects of O
      GlcNAcylation on biological functions of CARM1 were undetermined. In the present
      study, we describe the comprehensive mapping of CARM1 post-translational
      modification (PTM) using top-down MS. We found that all detectable recombinant
      CARM1 expressed in human embryonic kidney (HEK293T) cells is automethylated as we
      previously reported and that about 50% of this automethylated CARM1 contains a
      single O-linked-beta-N-acetylglucosamine (O-GlcNAc) moiety [31]. The O-GlcNAc
      moiety was mapped by MS to four possible sites (Ser595, Ser598, Thr601 and
      Thr603) in the C-terminus of CARM1. Mutation of all four sites [CARM1 quadruple
      mutant (CARM1QM)] markedly decreased O-GlcNAcylation, but did not affect protein
      stability, dimerization or cellular localization of CARM1. Moreover, CARM1QM
      elicits similar co-activator activity as CARM1 wild-type (CARM1WT) on a few
      transcription factors known to be activated by CARM1. However, O-GlcNAc-depleted
      CARM1 generated by wheat germ agglutinin (WGA) enrichment, O-GlcNAcase (OGA)
      treatment and mutation of putative O-GlcNAcylation sites displays different
      substrate specificity from that of CARM1WT. Our findings suggest that O
      GlcNAcylation of CARM1 at its C-terminus is an important determinant for CARM1
      substrate specificity. 

PMID- 25585346
TI  - Different MOG(35-55) concentrations induce distinguishable inflammation through
      early regulatory response by IL-10 and TGF-beta in mice CNS despite unchanged
      clinical course.
AB  - Multiple sclerosis (MS) shows distinct clinical courses. Experimental autoimmune
      encephalomyelitis (EAE), a model to study multiple sclerosis, can be induced by
      different protocols, which show distinct cytokine and antibody production. The
      factors involved in this heterogeneity remain unclear. The relevance of MOG
      concentration in triggering a regulatory response in the chronic model of EAE is
      imprecise. The aim of this study was investigate if 100 or 300 MUg of MOG(35-55)
      could induce different EAE profiles. Modifications in the concentration of MOG
      were able to change the patterns of chemokines, cytokines, percentage of cells,
      inflammatory infiltrate and the development of a regulatory response. However,
      these changes were unable to modify the intensity of response, which explains the
      chronic progression of the disease in both concentrations. The results presented
      in this study contribute to understanding the intricate mechanisms that trigger
      EAE and provide insights into the pathogenesis of various forms of MS.

PMID- 25585347
TI  - Iopromide in combination with IFN-gamma induces the activation of HMC-1 cells via
      IL-4 and MCP-1 expression.
AB  - In this study, we investigated whether IFN-gamma has a role in contrast-medium
      induced adverse reactions. Iopromide, a nonionic iodinated contrast agent,
      slightly induced mast cell proliferation and significantly increased the
      expression of IL-4 and MCP-1 at low doses. The pretreatment of cells with IFN
      gamma dramatically increased the expression of iopromide-induced IL-4 and MCP-1.
      An evaluation of mast cell activator secretion revealed that IFN-gamma- or IL-4
      pretreated HMC-1 cells released dramatically increased levels of beta
      hexosaminidase and histamine when stimulated with iopromide. We also found that
      the migration of EoL-1 and THP-1 cells was significantly increased in culture
      conditions with iopromide-stimulated IL-4-pretreated HMC-1 cells. Taken together,
      our findings suggest that measuring IFN-gamma or IL-4 levels in serum would be
      helpful as a potential biomarker of adverse patient reactions and that blocking
      IFN-gamma or IL-4 may be crucial in preventing the delayed allergy-like reaction
      induced by contrast medium in patients with various diseases. 

PMID- 25585348
TI  - An update on the management of chronic hepatitis C: 2015 Consensus guidelines
      from the Canadian Association for the Study of the Liver.
AB  - Chronic hepatitis C remains a significant medical and economic burden in Canada,
      affecting nearly 1% of the population. Since the last Canadian consensus
      conference on the management of chronic hepatitis C, major advances have occurred
      that warrant a review of recommended management approaches for these patients.
      Specifically, direct-acting antiviral agents with dramatically improved rates of
      virological clearance compared with standard therapy have been developed and
      interferon-free, all-oral antiviral regimens have been approved. In light of this
      new evidence, an update to the 2012 Canadian Association for the Study of the
      Liver consensus guidelines on the management of hepatitis C was produced. The
      present document reviews the epidemiology of hepatitis C in Canada, preferred
      diagnostic testing approaches and recommendations for the treatment of
      chronically infected patients with the newly approved antiviral agents, including
      those who have previously failed peginterferon and ribavirin-based therapy. In
      addition, recommendations are made regarding approaches to reducing the burden of
      hepatitis C in Canada. 

PMID- 25585349
TI  - Green tea polyphenol (-)-epigallocatechin-3-gallate triggered hepatotoxicity in
      mice: responses of major antioxidant enzymes and the Nrf2 rescue pathway.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been
      suggested to have numerous health-promoting effects. On the other hand, high-dose
      EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the
      responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2
      related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming
      mice. At a non-lethal toxic dose (75mg/kg, i.p.), repeated EGCG treatments
      markedly decreased the levels of superoxide dismutase, catalase, and glutathione
      peroxidase. As a rescue response, the nuclear distribution of Nrf2 was
      significantly increased; a battery of Nrf2-target genes, including heme oxygenase
      1 (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase
      (GST), and those involved in glutathione and thioredoxin systems, were all up
      regulated. At the maximum tolerated dose (45mg/kg, i.p.), repeated EGCG
      treatments did not disturb the major antioxidant defense. Among the above
      mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up
      regulated, suggesting a comprehensive and extensive activation of Nrf2-target
      genes principally occurs at toxic levels of EGCG. At a lethal dose (200mg/kg,
      i.p.), a single EGCG treatment dramatically decreased not only the major
      antioxidant defense but also the Nrf2-target genes, demonstrating that toxic
      levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the
      mechanism of EGCG-triggered hepatotoxicity involves suppression of major
      antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for
      counteracting EGCG toxicity. 

PMID- 25585351
TI  - Codeine Ultra-rapid Metabolizers: Age Appears to be a Key Factor in Adverse
      Effects of Codeine.
AB  - Codeine is widely used as an analgesic drug. Taking into account the high
      consumption of codeine, only few fatal adverse events have been published. A
      number of reports, where neonates and children showed serious or fatal adverse
      reactions, led to a restriction of the use of codeine in this patient group.
      Therefore, we reviewed the safety of codeine in adults. PubMed was systematically
      searched for clinical studies and case reports, with a special focus on CYP2D6,
      the enzyme that converts codeine to morphine and exhibits genetic
      polymorphism.181 cases were identified in adults in conjunction with serious or
      lethal effects of codeine. In the vast majority of cases, codeine was used in
      combination with other drugs by drug-dependent individuals or with a suicidal
      intent. Only 2 cases were found where ultra-rapid metabolizers experienced severe
      non-lethal adverse events. This is far less than would be predicted from the
      number of cases reported in children. The discrepancy may be explained by
      developmental changes in the disposition of codeine.The strategy of regulatory
      authorities to restrict access to codeine for infants and young children, the
      apparent highest risk group, has a factual and pharmacological rationale. By the
      same standards, there is no need for restrictions for adult use of codeine. 

PMID- 25585350
TI  - Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later
      life Notch1-mediated T cell development and leukemogenesis.
AB  - Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating
      mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo
      p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl
      hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch
      signaling pathways has previously been observed. Given the importance of Notch
      signaling in thymocyte development and T-ALL disease progression, we hypothesized
      that the activated AHR potentiates disease initiation and progression in an in
      vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult
      and developmental exposure paradigms to TCDD in mice expressing a constitutively
      active Notch1 transgene (Notch(ICN-TG)). Following exposure of adult Notch(ICN
      TG) mice to a single high dose of TCDD, we observed a significant increase in the
      efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3MUg/kg
      of TCDD throughout gestation and lactation to elucidate effects of developmental
      AHR activation on later-life T cell development and T-ALL-like thymoma
      susceptibility induced by Notch1. We found that the vehicle-exposed Notch(ICN-TG)
      offspring have a peripheral T cell pool heavily biased toward the CD4 lineage,
      while TCDD-exposed Notch(ICN-TG) offspring were biased toward the CD8 lineage.
      Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased
      splenomegaly and B to T cell ratios indicative of disease, mice developmentally
      exposed to TCDD were largely protected from disease. These studies support a
      model where developmental AHR activation attenuates later-life Notch1-dependent
      impacts on thymocyte development and disease progression. 

PMID- 25585353
TI  - Effect of simulated fall heat waves on cold hardiness and winter survival of
      hemlock looper, Lambdina fiscellaria (Lepidoptera: Geometridae).
AB  - The hemlock looper (Lambdina fiscellaria) is an important pest of eastern
      Canadian forests. The ongoing climate warming could modify the seasonal ecology
      of this univoltine species that lays eggs at the end of summer and overwinters at
      this stage. Indeed, the increase in frequency and intensity of extreme climatic
      events such as fall heat waves could interfere with the winter metabolism of the
      hemlock looper. Moreover, the host plant quality, which influences the quantity
      of insect energetic reserves, the geographic origin of populations and the
      conditions prevailing during the cold acclimation period, could cause various
      responses of this pest to climate warming. The main objective of this study is to
      determine the impact of these factors on hemlock looper winter biology. In
      October 2010, hemlock looper eggs initially collected from two geographic areas
      in the province of Quebec, and from parents reared on two host plants, were
      exposed to fall heat waves of different intensities during 5 consecutive days.
      Supercooling points and cryoprotectant levels were measured on eggs on four
      different dates in 2010-2011 and survival rate was measured in April 2011. Our
      results show that hemlock looper eggs have a very low supercooling point and high
      levels of trehalose, glucose and mannitol in September and November. However,
      there is no clear relationship between the concentration of these compounds and
      the decrease in supercooling points. Contents in trehalose, glucose and mannitol
      were significantly influenced by fall heat waves and by the origin of the
      population. Winter survival of eggs from the temperate population was negatively
      affected by strong heat waves while the boreal population was not affected. This
      study suggests that the metabolism and winter survival of temperate hemlock
      looper populations in Quebec will be more affected by fall heat waves that will
      increase in frequency due to climate change, than boreal populations. 

PMID- 25585354
TI  - Betulinic acid attenuates renal oxidative stress and inflammation in experimental
      model of murine polymicrobial sepsis.
AB  - Sepsis is a common cause of acute kidney injury (AKI) and is associated with
      substantial morbidity and mortality. Objective of the study was to evaluate the
      effect of betulinic acid, a triterpenoid in sepsis-induced AKI using cecal
      ligation puncture (CLP) mouse model. Mice subjected to CLP developed histologic
      AKI at 18h after CLP. There was an increase in renal proinflammatory response
      (nuclear factor-kappa B expression, tumor necrosis factor-alpha, interleukin (IL)
      6 and IL-10), matrix metalloproteinase-9, plasma creatinine, renal neutrophil
      gelatinase-associated lipocalin and oxidant stress response (malondialdehyde,
      inducible nitric oxide synthase, total nitrite and superoxide); decrease in anti
      oxidant levels (superoxide dismutase and catalase) at 18h of CLP. However, BA
      pretreatment at the doses of 10 and 30mg/kg prevented the CLP-induced kidney
      damage by restoring the aforementioned inflammatory mediators, oxidant and anti
      oxidant imbalance. These evidences suggest that, the protective effects of BA on
      kidney are associated with defending action against inflammatory and oxidative
      stress response in CLP mice and BA could be potential therapeutic agent in sepsis
      induced AKI. 

PMID- 25585352
TI  - Perturbations in dopamine synthesis lead to discrete physiological effects and
      impact oxidative stress response in Drosophila.
AB  - The impact of mutations in four essential genes involved in dopamine (DA)
      synthesis and transport on longevity, motor behavior, and resistance to oxidative
      stress was monitored in Drosophila melanogaster. The fly lines used for this
      study were: (i) a loss of function mutation in Catecholamines up (Catsup(26)),
      which is a negative regulator of the rate limiting enzyme for DA synthesis, (ii)
      a mutant for the gene pale (ple(2)) that encodes for the rate limiting enzyme
      tyrosine hydroxylase (TH), (iii) a mutant for the gene Punch (Pu(Z22)) that
      encodes guanosine triphosphate cyclohydrolase, required for TH activity, and (iv)
      a mutant in the vesicular monoamine transporter (VMAT(Delta14)), which is
      required for packaging of DA as vesicles inside DA neurons. Median lifespans of
      ple(2), Pu(Z22) and VMAT(Delta14) mutants were significantly decreased compared
      to Catsup(26) and wild type controls that did not significantly differ between
      each other. Catsup(26) flies survived longer when exposed to hydrogen peroxide
      (80 MUM) or paraquat (10mM) compared to ple(2), Pu(Z22) or VMAT(Delta14) and
      controls. These flies also exhibited significantly higher negative geotaxis
      activity compared to ple(2), Pu(Z22), VMAT(Delta14) and controls. All mutant
      flies demonstrated rhythmic circadian locomotor activity in general, albeit
      Catsup(26) and VMAT(Delta14) flies had slightly weaker rhythms. Expression
      analysis of some key antioxidant genes revealed that glutathione S-transferase
      Omega-1 (GSTO1) expression was significantly up-regulated in all DA synthesis
      pathway mutants and especially in Catsup(26) and VMAT(Delta14) flies at both mRNA
      and protein levels. Taken together, we hypothesize that DA could directly
      influence GSTO1 transcription and thus play a significant role in the regulation
      of response to oxidative stress. Additionally, perturbations in DA synthesis do
      not appear to have a significant impact on circadian locomotor activity rhythms
      per se, but do have an influence on general locomotor activity levels.

PMID- 25585355
TI  - Enteric-coating of pulsatile-release HPC capsules prepared by injection molding.
AB  - Capsular devices based on hydroxypropyl cellulose (Klucel(r) LF) intended for
      pulsatile release were prepared by injection molding (IM). In the present work,
      the possibility of exploiting such capsules for the development of colonic
      delivery systems based on a time-dependent approach was evaluated. For this
      purpose, it was necessary to demonstrate the ability of molded cores to undergo a
      coating process and that coated systems yield the desired performance (gastric
      resistance). Although no information was available on the coating of IM
      substrates, some issues relevant to that of commercially-available capsules are
      known. Thus, preliminary studies were conducted on molded disks for screening
      purposes prior to the spray-coating of HPC capsular cores with Eudragit(r) L 30 D
      55. The ability of the polymeric suspension to wet the substrate, spread, start
      penetrating and initiate hydration/swelling, as well as to provide a
      gastroresistant barrier was demonstrated. The coating of prototype HPC capsules
      was carried out successfully, leading to coated systems with good technological
      properties and able to withstand the acidic medium with no need for sealing at
      the cap/body joint. Such systems maintained the original pulsatile release
      performance after dissolution of the enteric film in pH 6.8 fluid. Therefore,
      they appeared potentially suitable for the development of a colon delivery
      platform based on a time-dependent approach. 

PMID- 25585356
TI  - A Src-family-tyrosine kinase, Lyn, is required for efficient IFN-beta expression
      in pattern recognition receptor, RIG-I, signal pathway by interacting with IPS-1.
AB  - Retinoic acid-inducible gene I (RIG-I) plays an important role in antiviral
      immunity as a cytosolic receptor recognizing invading viruses. The activation of
      downstream signaling pathways led by IFN-beta promoter stimulator-1 (IPS-1), an
      adaptor, is known to culminate in the activation of IRFs and the expression of
      type I interferons. However, the role of Src-family-tyrosine kinases (STKs) in
      the RIG-I signaling pathway has not been fully evaluated. Through a combined
      approach of immunoprecipitation and micro reversed phase liquid chromatography
      tandem mass spectrometry (RPLC-MS/MS) analysis, we established that Lyn, one of
      the STKs, is associated with RIG-I in macrophages. The association of Lyn and RIG
      I was confirmed by co-immunoprecipitation study with 293T cells overexpressing
      Lyn and RIG-I. Suppression of Lyn by siRNA knockdown or a pharmacological
      inhibitor (PP2) resulted in the attenuation of IRF3 activation and IFN-beta
      expression induced by short poly I:C, a RIG-I agonist, in macrophages. Lyn
      activation, as determined by phosphorylation of Tyr396 residue, was observed upon
      short poly I:C stimulation in the mitochondria of macrophages. Short poly I:C
      induced the formation of speckle-like aggregates of Lyn, which are prominent in
      mitochondria. Lyn associated with IPS-1, an adaptor protein of RIG-I, which
      resides on mitochondria membrane. Helicase domain of RIG-I and CARD of IPS-1 are
      responsible for the interaction with Lyn while SH3 and SH2 domains in Lyn are
      required for the association with RIG-I and IPS-1. Collectively, our results
      indicate that Lyn plays a positive regulatory role in RIG-I-mediated interferon
      expression as a downstream component of IPS-1. They provide further information
      as to how tyrosine kinases such as STKs play a role in the regulation of
      antiviral immunity. 

PMID- 25585358
TI  - Systematic review and meta-analysis of randomized controlled trials comparing
      compound danshen dripping pills and isosorbide dinitrate in treating angina
      pectoris.

PMID- 25585357
TI  - The molecular and immunochemical expression of innexins in the yellow fever
      mosquito, Aedes aegypti: insights into putative life stage- and tissue-specific
      functions of gap junctions.
AB  - Gap junctions (GJ) mediate direct intercellular communication by forming channels
      through which certain small molecules and/or ions can pass. Connexins, the
      proteins that form vertebrate GJ, are well studied and known to contribute to
      neuronal, muscular and epithelial physiology. Innexins, the GJ proteins of
      insects, have only recently received much investigative attention and many of
      their physiological roles remain to be determined. Here we characterize the
      molecular expression of six innexin (Inx) genes in the yellow fever mosquito
      Aedes aegypti (AeInx1, AeInx2, AeInx3, AeInx4, AeInx7, and AeInx8) and the
      immunochemical expression of one innexin protein, AeInx3, in the alimentary
      canal. We detected the expression of no less than four innexin genes in each
      mosquito life stage (larva, pupa, adult) and tissue/body region from adult males
      and females (midgut, Malpighian tubules, hindgut, head, carcass, gonads),
      suggesting a remarkable potential molecular diversity of GJ in mosquitoes.
      Moreover, the expression patterns of some innexins were life stage and/or tissue
      specific, suggestive of potential functional specializations. Cloning of the four
      full-length cDNAs expressed in the Malpighian tubules of adult females (AeInx1,
      AeInx2, AeInx3, and AeInx7) revealed evidence for 1) alternative splicing of
      AeInx1 and AeInx3 transcripts, and 2) putative N-glycosylation of AeInx3 and
      AeInx7. Finally, immunohistochemistry of AeInx3 in the alimentary canal of larval
      and adult female mosquitoes confirmed localization of this innexin to the
      intercellular regions of Malpighian tubule and hindgut epithelial cells,
      suggesting that it is an important component of GJ in these tissues. 

PMID- 25585359
TI  - Determinants of medication adherence and blood pressure control among
      hypertensive patients in Hong Kong: a cross-sectional study.
AB  - INTRODUCTION: Despite effective treatments, suboptimal medication adherence
      substantially hinders blood pressure (BP) control among hypertensive patients.
      This study aimed to evaluate the determinants of medication adherence and BP
      control among hypertensive patients in Hong Kong. METHODS: A cross-sectional
      study was conducted. Adult patients aged>18years taking at least one type of
      antihypertensive drugs were recruited from four clinics in Hong Kong. Each
      patient completed a self-administered questionnaire, including socio-demographic
      variables and items related to knowledge, illness perception and medication
      adherence. Medication adherence was measured by the eight-item Morisky Medication
      Adherence Scale (MMAS-8), with a score>6 defined as "good adherence". BP was
      measured, and optimal control was defined as systolic BP<140mmHg and diastolic
      BP<90mmHg. RESULTS: Among 2445 patients, 55.1% and 52.5% had optimal medication
      adherence and BP control, respectively. Binary logistic regression analyses were
      conducted with optimal medication adherence and BP control, respectively, as the
      outcome variables. Advanced age (adjusted odds ratio [aOR] 1.012, 95% CI 1.002
      1.022, p=0.014), unemployment (aOR for employed 0.782, 95% CI 0.628-0.975,
      p=0.029), and good self-perceived health status (aOR 2.155, 95% CI 1.711-2.714,
      p<0.001) were associated with good adherence; whereas being married (aOR 1.265,
      95% CI 1.038-1.542, p=0.020) and having no co-morbidity (aOR for morbidity count
      0.713, 95% CI 0.639-0.796, p<0.001) were associated with optimal BP control.
      CONCLUSION: Evidence-based, adherence-enhancing interventions should be targeted
      on younger subjects; employed patients; and those with poor self-perceived health
      status. Patients who are single and those with comorbidities should be closely
      monitored for their BP control.

PMID- 25585360
TI  - Cardiac effects of acute exhaustive exercise in a rat model.
AB  - BACKGROUND: The role of physical exercise in the prevention and treatment of
      cardiovascular diseases has been well described, however, elevations in
      cardionecrotic biomarkers after prolonged exercise (i.e. ultramarathon running)
      were observed. We aimed at understanding the biochemical, molecular biological,
      structural and functional alterations in the heart after exhaustive exercise in a
      rat model. METHODS: Rats of the exercise group were forced to swim for 3h with 5%
      body weight (workload) attached to the tail, control rats were taken into the
      water for 5min. After a 2-hour recovery period we performed left ventricular (LV)
      pressure-volume analysis to investigate LV function and mechanoenergetics.
      Additionally, blood and myocardium samples were harvested for biochemical and
      histological examinations. Gene expression changes were detected by qRT-PCR.
      RESULTS: When compared to controls, elevated plasma levels of cardiac troponin T
      and creatine kinase were detected after exhaustive exercise. Histological
      analysis showed sporadic fragmentation of myocardial structure and leukocyte
      infiltration in the exercised group. We observed increased end-systolic volume,
      decreased ejection fraction, impaired contractility (preload recruitable stroke
      work) and mechanoenergetics (ventriculoarterial coupling, mechanical efficiency)
      of LV after exercise. Myocardial expression of major antioxidant enzymes was
      increased along with increased myocardial nitro-oxidative stress. Bax/Bcl-2 ratio
      and TUNEL staining showed enhanced apoptotic signaling. Exhaustive exercise also
      resulted in the dysregulation of the matrix metalloproteinase system.
      CONCLUSIONS: Excessive physical activity has an adverse effect on the heart. The
      observed functional impairment is associated with increased nitro-oxidative
      stress, enhanced apoptotic signaling and dysregulation of the matrix
      metalloproteinase system after exhaustive exercise.

PMID- 25585361
TI  - Transcatheter aortic valve implantation with a Direct Flow Medical valve in a
      patient with severe aortic regurgitation due to degenerated aortic stentless
      bioprosthesis.

PMID- 25585362
TI  - Co-registration of optical coherence tomography and X-ray angiography in
      percutaneous coronary intervention. the Does Optical Coherence Tomography
      Optimize Revascularization (DOCTOR) fusion study.
AB  - BACKGROUND: Intracoronary imaging provides accurate lesion delineation and
      precise measurements for sizing and positioning of coronary stents. During
      percutaneous coronary intervention (PCI), it may be challenging to identify
      corresponding segments between intracoronary imaging and angiography. Computer
      based online co-registration may aid the target segment identification. METHODS:
      The DOCTOR fusion study was a prospective, single arm, observational study
      including patients admitted for elective PCI. Optical coherence tomography (OCT)
      was acquired pre-stent implantation for sizing of stents. The operator
      subsequently indicated on the angiogram the target area as identified by OCT.
      Computer based co-registration was performed on-line immediately after pre-stent
      acquisition to assess feasibility. The cumulated numerical difference between
      operator based, and computer based co-registration was assessed as the "Operator
      Registration Error". The operator implanted the stent blind to the co-registrated
      angiogram. The difference between the co-registered stent border positions and
      the actual stent deployment border positions was the "Geographic Miss Distance".
      RESULTS: Twenty-two patients were included in the study. Two patients were
      excluded due to missing pre or post-OCT acquisitions. Online co-registration pre
      stenting was successful in all analyzed cases. The mean "Operator Registration
      Error" was 5.4+/-3.5mm. The mean "Geographic Miss Distance" was 5.4+/-2.6mm.
      Without access to the computer-based co-registration, segments of the target
      lesion indicated on OCT were left uncovered by stent in 14 patients (70%).
      CONCLUSION: Computer based online co-registration of OCT and angiography is
      feasible. Frequent inaccuracies in operator based registration indicate that
      computer aided co-registration may reduce errors in corresponding OCT findings to
      the angiogram.

PMID- 25585363
TI  - "A cold shower": electrical magnetic interference caused by water heater current
      leakage through shower water pipe inducing ICD shock.

PMID- 25585364
TI  - A resynchronized shunt: Biventricular pacing followed by acute clinical
      decompensation in a patient with misdiagnosed atrial septal defect.

PMID- 25585365
TI  - Postprandial left atrial filling is impaired in patients with large hiatal hernia
      and improves following surgical repair.

PMID- 25585366
TI  - Provisional main branch stenting with drug-eluting stents after drug-eluting
      balloon treatment of the side branch: a simple and durable technique for treating
      bifurcation lesions.

PMID- 25585367
TI  - Takotsubo cardiomyopathy, a new concept of cardiomyopathy: clinical features and
      pathophysiology.
AB  - Takotsubo cardiomyopathy, a new concept of cardiomyopathy, is characterized by
      transient cardiac dysfunction, commonly triggered by physical or emotional
      stress. Differential diagnosis is important, since takotsubo cardiomyopathy
      presents similar images to those shown in acute coronary syndrome, with ST
      segment elevation, T-wave inversion, QT-prolongation, and others on
      electrocardiogram. Typically, apical involvement with hypercontraction of basal
      left ventricle (apical type) is predominant, but atypical types involving basal,
      mid-ventricular, and right ventricular myocardium are also described. In-hospital
      death occurs at similar level with patients with acute coronary syndrome, but it
      is significantly affected by underlying diseases. This disease presents diverse
      cardiac complications in acute phase, such as life-threatening ventricular
      arrhythmias, pump failure, cardiac rupture, and systemic embolism. The pathogenic
      mechanism of this disease is still unclear but sympathetic hyperactivity, as well
      as coronary vasospasm, microcirculatory disorder, and estrogen deficiency, have
      been considered as one of the most likely pathogenic mechanism. Long-term
      prognosis is also largely unknown. Issues such as establishment of acute phase
      treatment, prediction of cardiac complications, and prophylactic measures against
      recurrence need to be further explored. 

PMID- 25585368
TI  - Transfemoral transcatheter aortic valve replacement compared with surgical
      replacement in patients with severe aortic stenosis and comparable risk: cost
      utility and its determinants.
AB  - OBJECTIVE: To evaluate cost-effectiveness of transfemoral TAVR vs surgical
      replacement (SAVR) and its determinants in patients with severe symptomatic
      aortic stenosis and comparable risk. METHODS: Patients were prospectively
      recruited in 6 Spanish hospitals and followed up over one year. We estimated
      adjusted incremental cost-effectiveness ratio (ICER) (Euros per quality-adjusted
      life-year [QALY] gained) using a net-benefit approach and assessed the
      determinants of incremental net-benefit of TAVR vs SAVR. RESULTS: We analyzed
      data on 207 patients: 58, 87 and 62 in the Edwards SAPIEN (ES) TAVR, Medtronic
      CoreValve (MC) TAVR and SAVR groups respectively. Average cost per patient of ES
      TAVR was ?8800 higher than SAVR and the gain in QALY was 0.036. The ICER was
      ?148,525/QALY. The cost of MC-TAVR was ?9729 higher than SAVR and the QALY
      difference was -0.011 (dominated). Results substantially changed in the following
      conditions: 1) in patients with high preoperative serum creatinine the ICERs were
      ?18,302/QALY and ?179,618/QALY for ES and MC-TAVR respectively; 2) a 30%
      reduction in the cost of TAVR devices decreased the ICER for ES-TAVR to
      ?32,955/QALY; and 3) imputing hospitalization costs from other European countries
      leads to TAVR being dominant. CONCLUSIONS: In countries with relatively low
      health care costs TAVR is not likely to be cost-effective compared to SAVR in
      patients with intermediate risk for surgery, mainly because of the high cost of
      the valve compared to the cost of hospitalization. TAVR could be cost-effective
      in specific subgroups and in countries with higher hospitalization costs.

PMID- 25585369
TI  - Reply to the letter "androgens in cardiac fibrosis and other cardiovascular
      mechanisms".

PMID- 25585370
TI  - Recurrent coronary arterial thromboses as the tip of the iceberg: the JAK2
      mutation-related disease.

PMID- 25585371
TI  - Is the electrocardiogram different in recurrent episodes of Takotsubo syndrome
      involving 2 different left ventricular territories in the same patient?

PMID- 25585372
TI  - Unexpected autopsy findings after sudden cardiac death: cardiovascular myxoedema
      and endocardial fibroelastosis.

PMID- 25585373
TI  - New electrocardiographic ST-elevation mimicking acute myocardial infarction in
      patients with non-fixed coronary artery stenosis: an important issue in the
      primary coronary interventional era.

PMID- 25585374
TI  - Cisplatin induced bradycardia.

PMID- 25585375
TI  - A particular malignant case of untreatable ventricular arrhythmias in
      arrhythmogenic cardiomyopathy.

PMID- 25585376
TI  - Network meta-analysis for evidence synthesis: what is it and why is it posed to
      dominate cardiovascular decision making?
AB  - Clinical decision-making requires synthesis of an often complex evidence base.
      Novel tools have been developed building upon the historical approach of
      reviewing the literature focusing on a specific topic. Stemming from qualitative
      reviews, systematic reviews of randomized clinical trials, typically encompassing
      statistical pooling with pairwise meta-analysis, have been devised and are now
      considered one of the uppermost ladders in the hierarchy of clinical evidence. In
      the last decade, the exponential growth in randomized trials and the introduction
      of original computational methods have created the novel opportunity to compare
      indirectly competing treatments, as well as combining effect estimates stemming
      from head-to-head trials with those obtained by indirect comparisons. These
      methods include adjusted indirect comparison meta-analysis, network meta
      analysis, and mixed treatment comparison. While still the focus of intense
      research and debate, they represent a powerful tool for evidence synthesis and
      comparative effectiveness in cardiovascular research, and thus are likely to
      become increasingly popular and impactful in shaping research agenda and clinical
      practice. This is clearly highlighted by a number of recent landmark network meta
      analyses on smoking cessation therapies, coronary stents, and management of
      patent foramen ovale in patients with history of cryptogenic stroke. 

PMID- 25585378
TI  - Sodium tanshinone IIA sulfonate for reduction of periprocedural myocardial injury
      during percutaneous coronary intervention (STAMP trial): rationale and design.

PMID- 25585377
TI  - Force-interval relationship predicts mortality in survivors of myocardial
      infarction with atrial fibrillation.
AB  - BACKGROUND: RR interval variations lead to beat-to-beat blood pressure
      differences through the myocardial force-interval relationship (FIR). In sinus
      rhythm, an altered FIR leads to post-extrasystolic potentiation (PESP) of
      systolic blood pressure, which has been shown to predict adverse outcome in
      survivors of acute myocardial infarction (MI). The purpose of this study was (1)
      to develop a parameter to assess the FIR in patients with atrial fibrillation
      (AF) and (2) to investigate its association with mortality in MI survivors
      suffering from AF. METHODS AND RESULTS: Thirty-two patients with acute MI and AF
      underwent 30-min recordings of ECG and continuous blood pressure. Episodes of a
      short RR interval (<80% of mean interval, RRi) preceding a long interval (>140%,
      RRi+1) were identified. The systolic pressures of the pulse waves following RRi
      and RRi+1 were labeled Pi and Pi+1. PESPAfib was calculated as (Pi+1-Pi)/(RRi+1
      RRi). During 5years of follow-up, 13 patients died. When PESPAfib was
      dichotomized at the median, mortality rates were 63% and 19% in patients with
      high and low PESPAfib. Hazard ratio for mortality was 4.88 for patients with high
      PESPAfib (1.33-17.84, p=0.004). The association of PESPAfib and mortality was
      independent from LVEF, age, diabetes mellitus or mean heart rate. CONCLUSIONS:
      PESPAfib, a measure for the FIR in patients with AF, can be derived from
      simultaneous ECG and blood pressure recordings. The results of this pilot study
      indicate that PESPAfib may be useful to predict adverse outcome in survivors of
      myocardial infarction suffering from AF.

PMID- 25585379
TI  - Silent coronary artery disease and incidence of cardiovascular and mortality
      events at different levels of glucose regulation; results of greater than a
      decade follow-up.
AB  - BACKGROUND: To determine the impact of silent coronary artery disease (CAD), in
      different levels of glucose regulation at baseline, i.e., those with normal
      fasting glucose/normal glucose tolerance (NFG/NGT), pre-diabetic and newly
      diagnosed diabetes mellitus (NDM), on cardiovascular disease (CVD) and total
      mortality in Iranian populations. METHODS: The study population included 1809
      individuals, aged >=50years, free of CVD at baseline with a median follow-up of
      12.1years. To explore the risk of CVD and mortality associated with the presence
      of silent CAD (as defined by Minnesota coding criteria for baseline
      electrocardiogram (ECG) in the absence of a history of CVD) in each of the
      glucose regulation categories, multivariate adjusted hazard ratios (HRs) were
      calculated for the presence of silent CAD, compared to the corresponding non
      silent CAD counterpart, as reference. RESULTS: During follow-up 382 CVD (321
      coronary heart disease) and 208 deaths (91 CVD mortality) occurred. Among the
      female population, the presence of silent CAD, independent of traditional risk
      factors, significantly increased the risk of CVD for population with NFG/NGT
      [2.40 (1.33-4.35)] and pre-diabetes [HR: 2.04 (1.14-3.63)]; however, in the male
      population the risk was significant for CVD [3.04 (1.53-6.05)] and mortality
      events [2.60 (1.22-5.56)] in the NDM population and marginally significant for
      mortality events in NFG/NGT. CONCLUSION: Different strategies should be
      considered for silent CAD in males and females with different levels of glucose
      regulation. It might be justified that screening ECG for prevention of CVD events
      should be considered mainly among non-diabetic women and men with NDM.

PMID- 25585381
TI  - AP-57/C10orf99 is a new type of multifunctional antimicrobial peptide.
AB  - Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the
      innate immune response that provides host defence at skin and mucosal surfaces.
      Here, we report the identification and characterization of a new type human AMPs,
      termed AP-57 (Antimicrobial Peptide with 57 amino acid residues), which is also
      known as C10orf99 (chromosome 10 open reading frame 99). AP-57 is a short basic
      amphiphilic peptide with four cysteines and a net charge +14 (MW = 6.52, PI =
      11.28). The highest expression of AP-57 were detected in the mucosa of stomach
      and colon through immunohistochemical assay. Epithelium of skin and esophagus
      show obvious positive staining and strong positive staining were also observed in
      some tumor and/or their adjacent tissues, such as esophagus cancer,
      hepatocellular carcinoma, squamous cell carcinoma and invasive ductal carcinoma.
      AP-57 exhibited broad-spectrum antimicrobial activities against Gram-positive
      Staphylococcus aureus, Actinomyce, and Fungi Aspergillus niger as well as
      mycoplasma and lentivirus. AP-57 also exhibited DNA binding capacity and specific
      cytotoxic effects against human B-cell lymphoma Raji. Compared with other human
      AMPs, AP-57 has its distinct characteristics, including longer sequence length,
      four cysteines, highly cationic character, cell-specific toxicity, DNA binding
      and tissue-specific expressing patterns. Together, AP-57 is a new type of
      multifunctional AMPs worthy further investigation.

PMID- 25585380
TI  - Angiogenesis in the developing spinal cord: blood vessel exclusion from neural
      progenitor region is mediated by VEGF and its antagonists.
AB  - Blood vessels in the central nervous system supply a considerable amount of
      oxygen via intricate vascular networks. We studied how the initial vasculature of
      the spinal cord is formed in avian (chicken and quail) embryos. Vascular
      formation in the spinal cord starts by the ingression of intra-neural vascular
      plexus (INVP) from the peri-neural vascular plexus (PNVP) that envelops the
      neural tube. At the ventral region of the PNVP, the INVP grows dorsally in the
      neural tube, and we observed that these vessels followed the defined path at the
      interface between the medially positioned and undifferentiated neural progenitor
      zone and the laterally positioned differentiated zone. When the interface between
      these two zones was experimentally displaced, INVP faithfully followed a newly
      formed interface, suggesting that the growth path of the INVP is determined by
      surrounding neural cells. The progenitor zone expressed mRNA of vascular
      endothelial growth factor-A whereas its receptor VEGFR2 and FLT-1 (VEGFR1), a
      decoy for VEGF, were expressed in INVP. By manipulating the neural tube with
      either VEGF or the soluble form of FLT-1, we found that INVP grew in a VEGF
      dependent manner, where VEGF signals appear to be fine-tuned by counteractions
      with anti-angiogenic activities including FLT-1 and possibly semaphorins. These
      results suggest that the stereotypic patterning of early INVP is achieved by
      interactions between these vessels and their surrounding neural cells, where VEGF
      and its antagonists play important roles. 

PMID- 25585382
TI  - Experimental evidence for the co-evolution of hominin tool-making teaching and
      language.
AB  - Hominin reliance on Oldowan stone tools-which appear from 2.5 mya and are
      believed to have been socially transmitted-has been hypothesized to have led to
      the evolution of teaching and language. Here we present an experiment
      investigating the efficacy of transmission of Oldowan tool-making skills along
      chains of adult human participants (N=184) using five different transmission
      mechanisms. Across six measures, transmission improves with teaching, and
      particularly with language, but not with imitation or emulation. Our results
      support the hypothesis that hominin reliance on stone tool-making generated
      selection for teaching and language, and imply that (i) low-fidelity social
      transmission, such as imitation/emulation, may have contributed to the ~700,000
      year stasis of the Oldowan technocomplex, and (ii) teaching or proto-language may
      have been pre-requisites for the appearance of Acheulean technology. This work
      supports a gradual evolution of language, with simple symbolic communication
      preceding behavioural modernity by hundreds of thousands of years.

PMID- 25585383
TI  - Functional hemichannels formed by human connexin 26 expressed in bacteria.
AB  - Gap-junction channels (GJCs) communicate the cytoplasm of adjacent cells and are
      formed by head-to-head association of two hemichannels (HCs), one from each of
      the neighbouring cells. GJCs mediate electrical and chemical communication
      between cells, whereas undocked HCs participate in paracrine signalling because
      of their permeability to molecules such as ATP. Sustained opening of HCs under
      pathological conditions results in water and solute fluxes that cannot be
      compensated by membrane transport and therefore lead to cell damage. Mutations of
      Cx26 (connexin 26) are the most frequent cause of genetic deafness and it is
      therefore important to understand the structure-function relationship of wild
      type and deafness-associated mutants. Currently available connexin HC expression
      systems severely limit the pace of structural studies and there is no simple high
      throughput HC functional assay. The Escherichia coli-based expression system
      presented in the present study yields milligram amounts of purified Cx26 HCs
      suitable for functional and structural studies. We also show evidence of
      functional activity of recombinant Cx26 HCs in intact bacteria using a new growth
      complementation assay. The E. coli-based expression system has high potential for
      structural studies and high-throughput functional screening of HCs.

PMID- 25585386
TI  - Electric-field-induced local structural phenomena in Pb-based ABO3-type relaxor
      ferroelectrics.
AB  - Lead-based ABO3-type relaxors and related systems have numerous applications in
      modern technical devices because of their remarkably high dielectric permittivity
      and piezoelectric/electroelastic and electro-optic coefficients. However, lead is
      not desired from an environmental point of view, and to switch to alternative
      alkali-, Ba-, or Bi-based relaxor systems, one must understand in great detail
      the structural mesoscopic order and coupling processes responsible for the
      outstanding performance and multifunctionality of the exemplar Pb-based
      compounds. To elucidate the type of ferroic coupling, three relaxor compounds
      PbSc0.5Ta0.5O3 (PST), Pb0.78Ba0.22Sc0.5Ta0.5O3 (PST-Ba), and PbSc0.5Nb0.5O3
      (PSN), were studied by polarized Raman scattering and acoustic emission at
      different temperatures and under an external electric field. The results reveal
      the coexistence of mesoscopic-scale ferroelectric and antiferroelectric coupling,
      which are predominantly related to B-site cations and A-site Pb cations,
      respectively. This suggests that the polar structural state of relaxors is
      frustrated ferrielectric. The presence of A-site cations with affinity to off
      center is significant for the development of mesoscopic-scale antiferroelectric
      order coexisting with the mesoscopic-scale ferroelectric order. 

PMID- 25585384
TI  - Ebola cases and health system demand in Liberia.
AB  - In 2014, a major epidemic of human Ebola virus disease emerged in West Africa,
      where human-to-human transmission has now been sustained for greater than 12
      months. In the summer of 2014, there was great uncertainty about the answers to
      several key policy questions concerning the path to containment. What is the
      relative importance of nosocomial transmission compared with community-acquired
      infection? How much must hospital capacity increase to provide care for the
      anticipated patient burden? To which interventions will Ebola transmission be
      most responsive? What must be done to achieve containment? In recent years,
      epidemic models have been used to guide public health interventions. But, model
      based policy relies on high quality causal understanding of transmission,
      including the availability of appropriate dynamic transmission models and
      reliable reporting about the sequence of case incidence for model fitting, which
      were lacking for this epidemic. To investigate the range of potential
      transmission scenarios, we developed a multi-type branching process model that
      incorporates key heterogeneities and time-varying parameters to reflect changing
      human behavior and deliberate interventions in Liberia. Ensembles of this model
      were evaluated at a set of parameters that were both epidemiologically plausible
      and capable of reproducing the observed trajectory. Results of this model
      suggested that epidemic outcome would depend on both hospital capacity and
      individual behavior. Simulations suggested that if hospital capacity was not
      increased, then transmission might outpace the rate of isolation and the ability
      to provide care for the ill, infectious, and dying. Similarly, the model
      suggested that containment would require individuals to adopt behaviors that
      increase the rates of case identification and isolation and secure burial of the
      deceased. As of mid-October, it was unclear that this epidemic would be contained
      even by 99% hospitalization at the planned hospital capacity. A new version of
      the model, updated to reflect information collected during October and November
      2014, predicts a significantly more constrained set of possible futures. This
      model suggests that epidemic outcome still depends very heavily on individual
      behavior. Particularly, if future patient hospitalization rates return to
      background levels (estimated to be around 70%), then transmission is predicted to
      remain just below the critical point around Reff = 1. At the higher
      hospitalization rate of 85%, this model predicts near complete elimination in
      March to June, 2015. 

PMID- 25585387
TI  - Piezoelectric activity in Perovskite ferroelectric crystals.
AB  - Perovskite ferroelectrics (PFs) have been the dominant piezoelectric materials
      for various electromechanical applications, such as ultrasonic transducers,
      sensors, and actuators, to name a few. In this review article, the development of
      PF crystals is introduced, focusing on the crystal growth and piezoelectric
      activity. The critical factors responsible for the high piezoelectric activity of
      PFs (i.e., phase transition, monoclinic phase, domain size, relaxor component,
      dopants, and piezoelectric anisotropy) are surveyed and discussed. A general
      picture of the present understanding on the high piezoelectricity of PFs is
      described. At the end of this review, potential approaches to further improve the
      piezoelectricity of PFs are proposed. 

PMID- 25585388
TI  - Variation of Piezoelectric properties and mechanisms across the relaxor
      like/Ferroelectric continuum in BiFeO3- (K0.5Bi0.5)TiO3-PbTiO3 ceramics.
AB  - 1- x - y)BiFeO3-x(K0.5Bi0.5)TiO3-yPbTiO3 (BFKBT- PT) piezoelectric ceramics were
      investigated across the compositional space and contrasted against the xBiFeO3-
      (1-x)(K0.5Bi0.5)TiO3 (BF-KBT) system, whereby a range of relaxor
      like/ferroelectric behavior was observed. Structural and piezoelectric properties
      were closely related to the PbTiO3 concentration; below a critical concentration,
      relaxor-like behavior was identified. The mechanisms governing the piezoelectric
      behavior were investigated with structural, electrical, and imaging techniques. X
      ray diffraction established that longrange non-centrosymmetric crystallographic
      order was evident above a critical PbTiO3 concentration, y > 0.1125. Commensurate
      with the structural analysis, electric-field-induced strain responses showed
      electrostrictive behavior in the PbTiO3-reduced compositions, with increased
      piezoelectric switching in PbTiO3-rich compositions. Positive-up-negative-down
      (PUND) analysis was used to confirm electric-field-induced polarization
      measurements, elucidating that the addition of PbTiO3 increased the switchable
      polarization and ferroelectric ordering. Piezoresponse force microscopy (PFM) of
      the BF-KBT-PT system exhibited typical domain patterns above a critical PbTiO3
      threshold, with no ferroelectric domains observed in the BF-KBT system in the
      pseudocubic region. Doping of BiFeO3-PbTiO3 has been unsuccessful in the search
      for hightemperature materials that offer satisfactory piezoelectric properties;
      however, this system demonstrates that the partial substitution of alternative
      end-members can be an effective method. The partial substitution of PbTiO3 into
      BF-KBT enables long-range non-centrosymmetric crystallographic order, resulting
      in increased polar order and TC, compared with the pseudocubic region. The search
      for novel high-temperature piezoelectric ceramics can therefore exploit the
      accommodating nature of the perovskite family, which allows significant variance
      in chemical and physical characters in the exploration of new solid-solutions. 

PMID- 25585385
TI  - Primary isolation strain determines both phage type and receptors recognised by
      Campylobacter jejuni bacteriophages.
AB  - In this study we isolated novel bacteriophages, infecting the zoonotic bacterium
      Campylobacter jejuni. These phages may be used in phage therapy of C. jejuni
      colonized poultry to prevent spreading of the bacteria to meat products causing
      disease in humans. Many C. jejuni phages have been isolated using NCTC12662 as
      the indicator strain, which may have biased the selection of phages. A large
      group of C. jejuni phages rely on the highly diverse capsular polysaccharide
      (CPS) for infection and recent work identified the O-methyl phosphoramidate
      modification (MeOPN) of CPS as a phage receptor. We therefore chose seven C.
      jejuni strains each expressing different CPS structures as indicator strains in a
      large screening for phages in samples collected from free-range poultry farms.
      Forty-three phages were isolated using C. jejuni NCTC12658, NCTC12662 and RM1221
      as host strains and 20 distinct phages were identified based on host range
      analysis and genome restriction profiles. Most phages were isolated using C.
      jejuni strains NCTC12662 and RM1221 and interestingly phage genome size (140 kb
      vs. 190 kb), host range and morphological appearance correlated with the
      isolation strain. Thus, according to C. jejuni phage grouping, NCTC12662 and
      NCTC12658 selected for CP81-type phages, while RM1221 selected for CP220-type
      phages. Furthermore, using acapsular ?kpsM mutants we demonstrated that phages
      isolated on NCTC12658 and NCTC12662 were dependent on the capsule for infection.
      In contrast, CP220-type phages isolated on RM1221 were unable to infect non
      motile ?motA mutants, hence requiring motility for successful infection. Hence,
      the primary phage isolation strain determines both phage type (CP81 or CP220) as
      well as receptors (CPS or flagella) recognised by the isolated phages. 

PMID- 25585389
TI  - Ferroelectric/Ferroelastic domain wall motion in dense and porous tetragonal lead
      zirconate titanate films.
AB  - Direct evidence of ferroelectric/ferroelastic domain reorientation is shown in
      Pb(Zr0.30Ti0.70)O3 (PZT30/70) thin films clamped to a rigid silicon substrate
      using in situ synchrotron X-ray diffraction during application of electric
      fields. Both dense films and films with 3 to 4 vol% porosity were measured. On
      application of electric fields exceeding the coercive field, it is shown that the
      porous films exhibit a greater volume fraction of ferroelastic domain
      reorientation (approximately 12 vol% of domains reorient at 3 times the coercive
      field, Ec) relative to the dense films (~3.5 vol% at 3Ec). Furthermore, the
      volume fraction of domain reorientation significantly exceeded that predicted by
      linear mixing rules. The high response of domain reorientation in porous films is
      discussed in the context of two mechanisms: local enhancement of the electric
      field near the pores and a reduction of substrate clamping resulting from the
      lowering of the film stiffness as a result of the porosity. Similar measurements
      during weak-field (subcoercive) amplitudes showed 0.6% volume fraction of domains
      reoriented for the porous films, which demonstrates that extrinsic effects
      contribute to the dielectric and piezoelectric properties. 

PMID- 25585390
TI  - Control of crystallographic texture and surface morphology of Pt/Tio2 templates
      for enhanced PZT thin film texture.
AB  - Optimized processing conditions for Pt/TiO2/SiO2/Si templating electrodes were
      investigated. These electrodes are used to obtain [111] textured thin film lead
      zirconate titanate (Pb[ZrxTi1-x ]O3 0 <= x <= 1) (PZT). Titanium deposited by dc
      magnetron sputtering yields [0001] texture on a thermally oxidized Si wafer. It
      was found that by optimizing deposition time, pressure, power, and the chamber
      pre-conditioning, the Ti texture could be maximized while maintaining low surface
      roughness. When oxidized, titanium yields [100]-oriented rutile. This seed layer
      has as low as a 4.6% lattice mismatch with [111] Pt; thus, it is possible to
      achieve strongly oriented [111] Pt. The quality of the orientation and surface
      roughness of the TiO2 and the Ti directly affect the achievable Pt texture and
      surface morphology. A transition between optimal crystallographic texture and the
      smoothest templating surface occurs at approximately 30 nm of original Ti
      thickness (45 nm TiO2). This corresponds to 0.5 nm (2 nm for TiO2) rms roughness
      as determined by atomic force microscopy and a full-width at half-maximum (FWHM)
      of the rocking curve 0002 (200) peak of 5.5/spl degrees/ (3.1/spl degrees/ for
      TiO2). A Pb[Zr0.52Ti 0.48]O3 layer was deposited and shown to template from the
      textured Pt electrode, with a maximum [111] Lotgering factor of 87% and a minimum
      111 FWHM of 2.4/spl degrees/ at approximately 30 nm of original Ti. 

PMID- 25585391
TI  - Composition-driven structural phase transitions in rare-earth-doped BiFeO3
      ceramics: a review.
AB  - Bismuth ferrite suffers from high leakage currents and the presence of a complex
      incommensurate spin cycloidal magnetic ordering, which has limited its commercial
      viability and has led researchers to investigate the functionality of doped
      BiFeO3 ceramics. In particular, the substitution of rare earths onto the Bi(3+)
      site of the perovskite lattice have been shown to lead to improved functional
      properties, including lower leakage currents and the suppression of the magnetic
      spin cycloid. There is particular interest in materials with compositions close
      to structural morphotropic phase boundaries, because these may lead to materials
      with enhanced electronic and magnetic properties analogous to the highly relevant
      PbZrO3- PbTiO3 solid solution. However, many contradictory crystal structures and
      physical behaviors are reported within the literature. To understand the
      structure-property relationships in these materials, it is vital that we first
      unravel the complex structural phase diagrams. We report here a comprehensive
      review of structural phase transitions in rare-earth-doped bismuth ferrite
      ceramics across the entire lanthanide series. We attempt to rationalize the
      literature in terms of the perovskite tool kit and propose an updated phase
      diagram based on an interpretation of the literature. 

PMID- 25585392
TI  - Robust polarization and strain behavior of Sm-modified BiFeO3 piezoelectric
      ceramics.
AB  - The route to phase-pure BiFeO3 (BFO) ceramics with excellent ferroelectric and
      electromechanical properties is severely impeded by difficulties associated with
      the perovskite phase stability during synthesis. This has meant that dopants and
      solid solutions with BFO have been investigated as a means of not only improving
      the functional properties, but also of improving the perovskite phase formation
      of BFO-based ceramics. The present work focuses on Sm-modified BFO ceramics of
      composition Bi0.88Sm0.12FeO3. The polarization and strain behaviors were
      investigated as a function of the phase composition, microstructure, and chemical
      composition. Addition of Sm reduces the susceptibility of the BFO perovskite to
      phase degradation by Si impurities. Si was observed to react into Sm-rich grains
      dispersed within the microstructure, with no large increases in the amount of
      bismuth-parasitic phases, namely Bi25FeO39 and Bi2Fe4O9. These as-prepared
      ceramics exhibited robust polarization behavior showing maximum remnant
      polarizations of ~40 to 50 MUC/cm(2). The electric-fieldinduced strain showed an
      appreciable stability in terms of the driving field frequency with maximum peak
      to-peak strains of ~0.3% and a coercive field of ~130 kV/cm. 

PMID- 25585393
TI  - Surface mapping of field-induced piezoelectric strain at elevated temperature
      employing full-field interferometry.
AB  - Piezoelectric actuators and sensors are widely used for flow control valves,
      including diesel injectors, ultrasound generation, optical positioning, printing,
      pumps, and locks. Degradation and failure of material and electrical properties
      at high temperature typically limits these applications to operating temperatures
      below 200 degrees C, based on the ubiquitous Pb(Zr,Ti)O3 ceramic. There are,
      however, many applications in sectors such as automotive, aerospace, energy and
      process control, and oil and gas, where the ability to operate at higher
      temperatures would open up new markets for piezoelectric actuation. Presented
      here is a review of recent progress and initial results toward a European effort
      to develop measurement techniques to characterize high-temperature materials.
      Full-field, multi-wavelength absolute length interferometry has, for the first
      time, been used to map the electric-field-induced piezoelectric strain across the
      surface of a PZT ceramic. The recorded variation as a function of temperature has
      been evaluated against a newly developed commercial single-beam system.
      Conventional interferometry allows measurement of the converse piezoelectric
      effect with high precision and resolution, but is often limited to a single
      point, average measurement and to limited sample environments because of optical
      aberrations in varying atmospheres. Here, the full-field technique allows the
      entire surface to be analyzed for strain and, in a bespoke sample chamber, for
      elevated temperatures. 

PMID- 25585395
TI  - Enhanced dielectric performance of BaTiO3/PVDF composites prepared by modified
      process for energy storage applications.
AB  - Ceramic-polymer composites have attracted extensive attention in electrical
      applications due to their high permittivity and low loss. In this work, we report
      the studies on the preparation and properties of barium titanate (BT)/
      poly(vinylidenefluoride) (PVDF) composite thin films. The composite film was
      prepared by a modified process rather than the conventional method. The modified
      process adopted ballmilling technique instead of the stirring method to disperse
      BT nanoparticles into PVDF solution. Scanning electron microscopy images of the
      obtained composites show that the BT nanoparticles are incorporated into the PVDF
      network and are well dispersed in the matrix. When the BT volume fraction is 30%,
      the permittivity and breakdown strength of the composites reach their optimal
      values and the energy density reaches maximum value (5.3 J/cm3), an increase of
      80% compared with that of the composites prepared using the stirring method.
      Another modification is the use of acetone and butanone mixed solution instead of
      N,N-dimethylformamide to dissolve the PVDF, which is beneficial to form pure
      alpha-PVDF composite films on the polyethylene terephthalate substrate by tape
      casting. The composites prepared by the modified process, with high permittivity
      and significantly enhanced breakdown strength, are useful candidates for energy
      storage applications. 

PMID- 25585396
TI  - Probability distributions and confidence intervals for simulated power law noise.
AB  - A method for simulating power law noise in clocks and oscillators is presented
      based on modification of the spectrum of white phase noise, then Fourier
      transforming to the time domain. Symmetric real matrices are introduced whose
      traces-the sums of their eigenvalues-are equal to the Allan variances, in
      overlapping or non-overlapping forms, as well as for the corresponding forms of
      the modified Allan variance. We show that the standard expressions for spectral
      densities, and their relations to Allan variance, are obtained with this method.
      The matrix eigenvalues determine probability distributions for observing a
      variance at an arbitrary value of the sampling interval tau, and hence for
      estimating confidence in the measurements. Examples are presented for the common
      power-law noises. Extension to other variances such as the Hadamard variance, and
      variances with dead time, are discussed. 

PMID- 25585394
TI  - Multi-frequency intravascular ultrasound (IVUS) imaging.
AB  - Acute coronary syndrome (ACS) is frequently associated with the sudden rupture of
      a vulnerable atherosclerotic plaque within the coronary artery. Several unique
      physiological features, including a thin fibrous cap accompanied by a necrotic
      lipid core, are the targeted indicators for identifying the vulnerable plaques.
      Intravascular ultrasound (IVUS), a catheter-based imaging technology, has been
      routinely performed in clinics for more than 20 years to describe the morphology
      of the coronary artery and guide percutaneous coronary interventions. However,
      conventional IVUS cannot facilitate the risk assessment of ACS because of its
      intrinsic limitations, such as insufficient resolution. Renovation of the IVUS
      technology is essentially needed to overcome the limitations and enhance the
      coronary artery characterization. In this paper, a multi-frequency intravascular
      ultrasound (IVUS) imaging system was developed by incorporating a higher
      frequency IVUS transducer (80 to 150 MHz) with the conventional IVUS (30-50 MHz)
      system. The newly developed system maintains the advantage of deeply penetrating
      imaging with the conventional IVUS, while offering an improved higher resolution
      image with IVUS at a higher frequency. The prototyped multifrequency catheter has
      a clinically compatible size of 0.95 mm and a favorable capability of automated
      image co-registration. In vitro human coronary artery imaging has demonstrated
      the feasibility and superiority of the multi-frequency IVUS imaging system to
      deliver a more comprehensive visualization of the coronary artery. This
      ultrasonic-only intravascular imaging technique, based on a moderate refinement
      of the conventional IVUS system, is not only cost-effective from the perspective
      of manufacturing and clinical practice, but also holds the promise of future
      translation into clinical benefits. 

PMID- 25585397
TI  - Dynamic tuning of MEMS resonators via electromechanical feedback.
AB  - This paper introduces an active electrical technique for dynamic tuning of MEMS
      resonators. The proposed technique is based on using the resonator output current
      to generate displacement or acceleration signals by integration or
      differentiation operations, respectively. The resulting signal is then scaled to
      generate an appropriate tuning signal. When applied to the resonator through
      additional signal ports, the tuning signal electrically modifies the equivalent
      mechanical stiffness or mass of the resonator, thereby tuning the resonance
      frequency in a bidirectional fashion depending on the polarity of the scaling.
      This tuning scheme has been applied to a piezoelectric AlN-on-Si BAW square
      resonator to tune its 14.2 MHz resonance frequency by 22 kHz, equivalent to 1550
      ppm. The proposed tuning technique can be applied to a wide range of MEMS
      resonators and resonant sensors, e.g., to compensate for temperature or process
      induced variations in their resonance frequencies. 

PMID- 25585399
TI  - Correction for frequency-dependent hydrophone response to nonlinear pressure
      waves using complex deconvolution and rarefactional filtering: application with
      fiber optic hydrophones.
AB  - Nonlinear acoustic signals contain significant energy at many harmonic
      frequencies. For many applications, the sensitivity (frequency response) of a
      hydrophone will not be uniform over such a broad spectrum. In a continuation of a
      previous investigation involving deconvolution methodology, deconvolution
      (implemented in the frequency domain as an inverse filter computed from frequency
      dependent hydrophone sensitivity) was investigated for improvement of accuracy
      and precision of nonlinear acoustic output measurements. Timedelay spectrometry
      was used to measure complex sensitivities for 6 fiber-optic hydrophones. The
      hydrophones were then used to measure a pressure wave with rich harmonic content.
      Spectral asymmetry between compressional and rarefactional segments was exploited
      to design filters used in conjunction with deconvolution. Complex deconvolution
      reduced mean bias (for 6 fiber-optic hydrophones) from 163% to 24% for peak
      compressional pressure (p+), from 113% to 15% for peak rarefactional pressure (p
      ), and from 126% to 29% for pulse intensity integral (PII). Complex deconvolution
      reduced mean coefficient of variation (COV) (for 6 fiber optic hydrophones) from
      18% to 11% (p+), 53% to 11% (p-), and 20% to 16% (PII). Deconvolution based on
      sensitivity magnitude or the minimum phase model also resulted in significant
      reductions in mean bias and COV of acoustic output parameters but was less
      effective than direct complex deconvolution for p+ and p-. Therefore,
      deconvolution with appropriate filtering facilitates reliable nonlinear acoustic
      output measurements using hydrophones with frequency-dependent sensitivity. 

PMID- 25585398
TI  - An adaptive displacement estimation algorithm for improved reconstruction of
      thermal strain.
AB  - Thermal strain imaging (TSI) can be used to differentiate between lipid and water
      based tissues in atherosclerotic arteries. However, detecting small lipid pools
      in vivo requires accurate and robust displacement estimation over a wide range of
      displacement magnitudes. Phase-shift estimators such as Loupas' estimator and
      time-shift estimators such as normalized cross-correlation (NXcorr) are commonly
      used to track tissue displacements. However, Loupas' estimator is limited by
      phase-wrapping and NXcorr performs poorly when the SNR is low. In this paper, we
      present an adaptive displacement estimation algorithm that combines both Loupas'
      estimator and NXcorr. We evaluated this algorithm using computer simulations and
      an ex vivo human tissue sample. Using 1-D simulation studies, we showed that when
      the displacement magnitude induced by thermal strain was >lambda/8 and the
      electronic system SNR was >25.5 dB, the NXcorr displacement estimate was less
      biased than the estimate found using Loupas' estimator. On the other hand, when
      the displacement magnitude was <=lambda/4 and the electronic system SNR was
      <=25.5 dB, Loupas' estimator had less variance than NXcorr. We used these
      findings to design an adaptive displacement estimation algorithm. Computer
      simulations of TSI showed that the adaptive displacement estimator was less
      biased than either Loupas' estimator or NXcorr. Strain reconstructed from the
      adaptive displacement estimates improved the strain SNR by 43.7 to 350% and the
      spatial accuracy by 1.2 to 23.0% (P < 0.001). An ex vivo human tissue study
      provided results that were comparable to computer simulations. The results of
      this study showed that a novel displacement estimation algorithm, which combines
      two different displacement estimators, yielded improved displacement estimation
      and resulted in improved strain reconstruction. 

PMID- 25585401
TI  - Accurate measurement of microbubble response to ultrasound with a diagnostic
      ultrasound scanner.
AB  - Ultrasound and microbubbles are often used to enhance drug delivery and the
      suggested mechanisms are extravasation and sonoporation. Drug delivery schemes
      with ultrasound and microbubbles at both low and high acoustic amplitudes have
      been suggested. A diagnostic ultrasound scanner may play a double role as both an
      imaging and a therapy device. It was not possible to accurately measure
      microbubble response with an ultrasound scanner for a large range of acoustic
      pressures and microbubble concentrations until now, mainly because of signal
      saturation issues. A method for continuously adjusting the receive gain of a
      scanner and limiting signal saturation was developed to accurately measure
      backscattered echoes from microbubbles for mechanical indexes (MIs) up to 2.1.
      The intensity of backscattered echoes from microbubbles increased quarticly with
      MI without reaching any limit. The signal intensity from microbubbles was found
      to be linear with concentration at both low and high MIs. However, at very high
      concentrations, acoustic shadowing occurs which limits the delivered acoustic
      pressure in deeper areas. The contrastto- tissue ratio was also measured and
      found to stay constant with MI. These results can be used to better guide drug
      delivery approaches and to also develop imaging techniques for therapy
      procedures. 

PMID- 25585400
TI  - Derivation and analysis of viscoelastic properties in human liver: impact of
      frequency on fibrosis and steatosis staging.
AB  - Commercially-available shear wave imaging systems measure group shear wave speed
      (SWS) and often report stiffness parameters applying purely elastic material
      models. Soft tissues, however, are viscoelastic, and higher-order material models
      are necessary to characterize the dispersion associated with broadband shear
      waves. In this paper, we describe a robust, model-based algorithm and use a
      linear dispersion model to perform shear wave dispersion analysis in
      traditionally difficult-to-image subjects. In a cohort of 135 non-alcoholic fatty
      liver disease patients, we compare the performance of group SWS with dispersion
      analysis-derived phase velocity c(200 Hz) and dispersion slope dc/df parameters
      to stage hepatic fibrosis and steatosis. Area under the ROC curve (AUROC)
      analysis demonstrates correlation between all parameters [group SWS, c(200 Hz),
      and, to a lesser extent dc/df ] and fibrosis stage, whereas no correlation was
      observed between steatosis stage and any of the material parameters.
      Interestingly, optimal AUROC threshold SWS values separating advanced liver
      fibrosis (>=F3) from mild-to-moderate fibrosis (<=F2) were shown to be frequency
      dependent, and to increase from 1.8 to 3.3 m/s over the 0 to 400 Hz shear wave
      frequency range. 

PMID- 25585402
TI  - Analytical phase-tracking-based strain estimation for ultrasound elasticity.
AB  - A new strain estimator for quasi-static elastography is presented, based on
      tracking of the analytical signal phase as a function of the external force. Two
      implementations are introduced: zero-phase search with moving window (SMW) and
      zero-phase band tracking using connected component labeling (CCL). Low analytical
      signal amplitude caused by local destructive interference is associated with
      large error in the phase trajectories, and amplitude thresholding can thus be
      used to terminate the phase tracking along a particular path. Interpolation is
      then applied to estimate displacement in the eliminated path. The paper describes
      first a mathematical analysis based on 1-D multi-scatter modeling, followed by a
      statistical study of the displacement and strain error. Simulation and experiment
      with an inhomogeneous phantom indicate that SMW and CCL are capable of reliably
      estimating tissue displacement and strain over a larger range of deformation than
      standard timedomain cross-correlation (SCC). Results also show that SMW is
      roughly 40 times faster than SCC with comparable or even better accuracy. CCL is
      slower than SMW, but more noise robust. Simulation assessment at compression
      level 3% and 6% with SNR 20 dB demonstrates average strain error for SMW and CCL
      of 10%, whereas SCC achieves 18%. 

PMID- 25585403
TI  - A methodology for estimating guided wave scattering patterns from sparse
      transducer array measurements.
AB  - Ultrasonic guided waves are one of the primary methods being investigated for
      structural health monitoring of plate-like components. A common practice is to
      collect measurements from a sparse transducer array using the pitch-catch method,
      which enables interrogation of defects from multiple directions. Thus, knowledge
      of how guided waves scatter from defects is very useful for detection,
      localization, and characterization of damage. One way to describe scattering
      patterns is with a matrix indexed by incident angle and scattered angle, and
      sparse array measurements essentially sample this matrix. A methodology is
      proposed in this paper to estimate the complete scattering matrix from these
      limited array measurements. First, recorded array signals are compensated for
      geometric spreading loss, wave packet spreading loss, and transducer differences.
      Initial scattering values are then extracted from the scattered wave packets
      after baseline subtraction and are augmented using transducer reciprocity and any
      a priori knowledge of defect geometric symmetry. Finally, radial basis function
      interpolation is performed on these values to obtain the complete scattering
      matrix. Scattering matrices are generated from experimental data by cutting
      notches of different lengths originating from a through-hole in an aluminum plate
      specimen that is instrumented with a sparse transducer array. The methodology is
      validated by laser vibrometry measurements performed on a nominally identical
      specimen for one notch length. 

PMID- 25585404
TI  - Differentially piezoresistive transduction of high-Q encapsulated SOI-MEMS
      resonators with sub-100 nm gaps.
AB  - A differentially piezoresistive (piezo-R) readout proposed for single-crystal
      silicon (SCS) microelectromechanical systems (MEMS) resonators is implemented in
      a foundrybased resonator platform, demonstrating effective feedthrough
      cancellation using just simple piezoresistors from the resonator supports while
      maximizing their capacitively transduced driving areas. The SCS resonators are
      fabricated by a CMOS foundry using an SOI-MEMS technology together with a
      polysilicon refill process. A high electromechanical coupling coefficient is
      attained by the use of 50-nm transducer gap spacing. Moreover, a vacuum package
      of the fabricated resonators is carried out through wafer-level bonding process.
      In this work, the corner supporting beams of the resonator serve not only
      mechanical supports but also piezoresistors for detecting the motional signal,
      hence substantially simplifying the overall resonator design to realize the piezo
      R sensing. In addition, the fabricated resonators are capable of either
      capacitive sensing or piezo-R detection under the same capacitive drive. To
      mitigate feedthrough signals from parasitics, a differential measurement
      configuration of the piezo-R transduction is implemented in this work, featuring
      more than 30-dB improvement on the feedthrough level as compared with the single
      ended piezo-R counterpart and purely capacitive sensing readout. Furthermore, the
      high-Q design of the mechanical supports is also investigated, offering Q more
      than 10 000 with efficient piezo-R transduction for MEMS resonators. 

PMID- 25585405
TI  - In vitro and in vivo tissue harmonic images obtained with parallel transmit
      beamforming by means of orthogonal frequency division multiplexing.
AB  - In classic pulse-echo ultrasound imaging, the data acquisition rate is limited by
      the speed of sound. To overcome this, parallel beamforming techniques in transmit
      (PBT) and in receive (PBR) mode have been proposed. In particular, PBT
      techniques, based on the transmission of focused beams, are more suitable for
      harmonic imaging because they are capable of generating stronger harmonics.
      Recently, orthogonal frequency division multiplexing (OFDM) has been investigated
      as a means to obtain parallel beamformed tissue harmonic images. To date, only
      numerical studies and experiments in water have been performed, hence neglecting
      the effect of frequencydependent absorption. Here we present the first in vitro
      and in vivo tissue harmonic images obtained with PBT by means of OFDM, and we
      compare the results with classic B-mode tissue harmonic imaging. The resulting
      contrast-to-noise ratio, here used as a performance metric, is comparable. A
      reduction by 2 dB is observed for the case in which three parallel lines are
      reconstructed. In conclusion, the applicability of this technique to
      ultrasonography as a means to improve the data acquisition rate is confirmed. 

PMID- 25585406
TI  - A new algorithm for time-delay estimation in ultrasonic echo signals.
AB  - Time-delay estimation determines the relative displacement between two ultrasound
      echo signals. In this paper, we propose a new time-delay estimation algorithm
      which uses only the sign function to obtain the corresponding timedelay estimate.
      The performance of the proposed algorithm was compared with two established
      algorithms, i.e., normalized cross-correlation (NCC) and sum of squared
      differences (SSD), using metrics such as statistical analysis and computational
      time. All simulated ultrasound echo signals were generated using ultrasound
      simulation software. The results indicated that overall, the proposed algorithm
      had similar accuracy and precision compared with the NCC and SSD algorithms;
      however, the computational time of the proposed algorithm was about 70% less than
      NCC and SSD, which showed a significant improvement. 

PMID- 25585407
TI  - Autonomous unobtrusive detection of mild cognitive impairment in older adults.
AB  - The current diagnosis process of dementia is resulting in a high percentage of
      cases with delayed detection. To address this problem, in this paper, we explore
      the feasibility of autonomously detecting mild cognitive impairment (MCI) in the
      older adult population. We implement a signal processing approach equipped with a
      machine learning paradigm to process and analyze real-world data acquired using
      home-based unobtrusive sensing technologies. Using the sensor and clinical data
      pertaining to 97 subjects, acquired over an average period of three years, a
      number of measures associated with the subjects' walking speed and general
      activity in the home were calculated. Different time spans of these measures were
      used to generate feature vectors to train and test two machine learning
      algorithms namely support vector machines and random forests. We were able to
      autonomously detect MCI in older adults with an area under the ROC curve of 0.97
      and an area under the precision-recall curve of 0.93 using a time window of 24
      weeks. This study is of great significance since it can potentially assist in the
      early detection of cognitive impairment in older adults. 

PMID- 25585408
TI  - Sparse dissimilarity-constrained coding for glaucoma screening.
AB  - OBJECTIVE: Glaucoma is an irreversible chronic eye disease that leads to vision
      loss. As it can be slowed down through treatment, detecting the disease in time
      is important. However, many patients are unaware of the disease because it
      progresses slowly without easily noticeable symptoms. Currently, there is no
      effective method for low-cost population-based glaucoma detection or screening.
      Recent studies have shown that automated optic nerve head assessment from 2-D
      retinal fundus images is promising for low-cost glaucoma screening. In this
      paper, we propose a method for cup to disc ratio (CDR) assessment using 2-D
      retinal fundus images. METHODS: In the proposed method, the optic disc is first
      segmented and reconstructed using a novel sparse dissimilarity-constrained coding
      (SDC) approach which considers both the dissimilarity constraint and the sparsity
      constraint from a set of reference discs with known CDRs. Subsequently, the
      reconstruction coefficients from the SDC are used to compute the CDR for the
      testing disc. RESULTS: The proposed method has been tested for CDR assessment in
      a database of 650 images with CDRs manually measured by trained professionals
      previously. Experimental results show an average CDR error of 0.064 and
      correlation coefficient of 0.67 compared with the manual CDRs, better than the
      state-of-the-art methods. Our proposed method has also been tested for glaucoma
      screening. The method achieves areas under curve of 0.83 and 0.88 on datasets of
      650 and 1676 images, respectively, outperforming other methods. CONCLUSION: The
      proposed method achieves good accuracy for glaucoma detection. SIGNIFICANCE: The
      method has a great potential to be used for large-scale population-based glaucoma
      screening.

PMID- 25585409
TI  - Modeling and estimation of tip contact force for steerable ablation catheters.
AB  - OBJECTIVE: The efficacy of catheter-based cardiac ablation procedures can be
      significantly improved if real-time information is available concerning contact
      forces between the catheter tip and cardiac tissue. However, the widely used
      ablation catheters are not equipped for force sensing. This paper proposes a
      technique for estimating the contact forces without direct force measurements by
      studying the changes in the shape of the deflectable distal section of a
      conventional 7-Fr catheter (henceforth called the "deflectable distal shaft," the
      "deflectable shaft," or the "shaft" of the catheter) in different loading
      situations. METHOD: First, the shaft curvature when the tip is moving in free
      space is studied and based on that, a kinematic model for the deflectable shaft
      in free space is proposed. In the next step, the shaft shape is analyzed in the
      case where the tip is in contact with the environment, and it is shown that the
      curvature of the deflectable shaft provides useful information about the loading
      status of the catheter and can be used to define an index for determining the
      range of contact forces exerted by the ablation tip. RESULTS: Experiments with
      two different steerable ablation catheters show that the defined index can detect
      the range of applied contact forces correctly in more than 80% of the cases.
      Based on the proposed technique, a framework for obtaining contact force
      information by using the shaft curvature at a limited number of points along the
      deflectable shaft is constructed. CONCLUSION: The proposed kinematic model and
      the force estimation technique can be implemented together to describe the
      catheter's behavior before contact, detect tip/tissue contact, and determine the
      range of contact forces. SIGNIFICANCE: This study proves that the flexibility of
      the catheter's distal shaft provides a means of estimating the force exerted on
      tissue by the ablation tip.

PMID- 25585411
TI  - Motion Robust Remote-PPG in Infrared.
AB  - Current state-of-the-art remote photoplethysmography (rPPG) algorithms are
      capable of extracting a clean pulse signal in ambient light conditions using a
      regular color camera, even when subjects move significantly. In this study, we
      investigate the feasibility of rPPG in the (near)-infrared spectrum, which
      broadens the scope of applications for rPPG. Two camera setups are investigated:
      one setup consisting of three monochrome cameras with different optical filters,
      and one setup consisting of a single RGB camera with a visible light blocking
      filter. Simulation results predict the monochrome setup to be more motion robust,
      but this simulation neglects parallax. To verify this, a challenging benchmark
      dataset consisting of 30 videos is created with various motion scenarios and skin
      tones. Experiments show that both camera setups are capable of accurate pulse
      extraction in all motion scenarios, with an average SNR of +6.45 and +7.26 dB,
      respectively. The single camera setup proves to be superior in scenarios
      involving scaling, likely due to parallax of the multicamera setup. To further
      improve motion robustness of the RGB camera, dedicated LED illumination with two
      distinct wavelengths is proposed and verified. This paper demonstrates that
      accurate rPPG measurements in infrared are feasible, even with severe subject
      motion. 

PMID- 25585410
TI  - An integrated widefield imaging and spectroscopy system for contrast-enhanced,
      image-guided resection of tumors.
AB  - Tumor recurrence following surgery is a common and unresolved medical problem of
      great importance since surgery is the most widely used treatment for solid-mass
      tumors worldwide. A contributing factor to tumor recurrence is the presence of
      residual tumor remaining at or near the surgical site following surgery. GOAL:
      The primary objective of this study was to develop and evaluate an image-guided
      surgery system based on a near-infrared, handheld excitation source and
      spectrograph in combination with a widefield video imaging system. METHODS: This
      system was designed to detect the fluorescence of near-infrared contrast agents
      and, in particular, indocyanine green (ICG). The imaging system was evaluated for
      its optical performance and ability to detect the presence of ICG in tumors in an
      ectopic murine tumor model as well as in spontaneous tumors arising in canines.
      RESULTS: In both settings, an intravenous ICG infusion provided tumor contrast.
      In both the murine models and surgical specimens from canines, ICG preferentially
      accumulated in tumor tissue compared to surrounding normal tissue. The resulting
      contrast was sufficient to distinguish neoplasia from normal tissue; in the
      canine surgical specimens, the contrast was sufficient to permit identification
      of neoplasia on the marginal surface of the specimen. CONCLUSION: These results
      demonstrate a unique concept in image-guided surgery by combining local
      excitation and spectroscopy with widefield imaging. SIGNIFICANCE: The ability to
      readily detect ICG in canines with spontaneous tumors in a clinical setting
      exemplifies the potential for further clinical translation; the promising results
      of detecting neoplasia on the marginal specimen surface underscore the clinical
      utility.

PMID- 25585412
TI  - RoboJockey: Designing an Entertainment Experience with Robots.
AB  - The RoboJockey entertainment system consists of a multitouch tabletop interface
      for multiuser collaboration. RoboJockey enables a user to choreograph a mobile
      robot or a humanoid robot by using a simple visual language. With RoboJockey, a
      user can coordinate the mobile robot's actions with a combination of back,
      forward, and rotating movements and coordinate the humanoid robot's actions with
      a combination of arm and leg movements. Every action is automatically performed
      to background music. RoboJockey was demonstrated to the public during two pilot
      studies, and the authors observed users' behavior. Here, they report the results
      of their observations and discuss the RoboJockey entertainment experience. 

PMID- 25585413
TI  - Upper-Limb Function Assessment Using VBBTs for Stroke Patients.
AB  - Evaluating and quantifying the upper-limb functions are essential to planning
      effective patient rehabilitation. The box and block test (BBT) is a conventional,
      simple, and easy-to-apply assessment tool that is used in hospitals, and previous
      studies have demonstrated its usefulness in stroke rehabilitation. Using a
      conventional depth-sensing camera, the authors developed a virtual box and block
      test (VBBT) system for hand, finger, and grasping assessments based on the BBT
      used for the grasping ability test in hospitals. Such a virtual upper-limb
      function assessment tool that can be implemented in a home setting could be a key
      component in a home-based virtual rehabilitation system. Comparison results
      between the real and virtual BBTs show the possibilities for virtualizing
      conventional and unsupervised assessments. 

PMID- 25585414
TI  - Vertebroplasty Performance on Simulator for 19 Surgeons Using Hierarchical Task
      Analysis.
AB  - We present a unique simulator-based methodology for assessing both technical and
      nontechnical (cognitive) skills for surgical trainees while immersed in a
      complete medical simulation environment. Further, we have included two crisis
      scenarios which allow for the evaluation of the effect of cognitive strategy
      selection on the low-level surgical skills. Training these mixed-mode scenarios
      can thereby be evaluated on our platform, allowing for improved assessment and a
      stronger foundation for credentialing, with the potential to reduce the
      occurrence of adverse events in the operating room. Scientific evaluation and
      validation of our work is conducted together with 19 junior surgeons in order to
      achieve the following goals: 1) to provide a qualitative measure of usability, 2)
      to assess vertebroplasty technical performance of the surgeon, and 3) to explore
      the relationship between mental workload and surgical performance during crisis.
      Our results indicate that: 1) the surgeons scored the face validity of our
      modeled simulation environment very highly ( 4.68 +/-0.48, using a 5-point Likert
      scale), 2) surgeon training enabled completion of tasks more quickly, and 3) the
      introduction of crisis scenarios negatively affected the surgeons' objective
      performance. Taken together, our results underscore the need to develop realistic
      simulation environments that prepare young residents to respond to emergent
      events in the operating room. 

PMID- 25585415
TI  - A Framework for Automated Spine and Vertebrae Interpolation-Based Detection and
      Model-Based Segmentation.
AB  - Automated and semi-automated detection and segmentation of spinal and vertebral
      structures from computed tomography (CT) images is a challenging task due to a
      relatively high degree of anatomical complexity, presence of unclear boundaries
      and articulation of vertebrae with each other, as well as due to insufficient
      image spatial resolution, partial volume effects, presence of image artifacts,
      intensity variations and low signal-to-noise ratio. In this paper, we describe a
      novel framework for automated spine and vertebrae detection and segmentation from
      3-D CT images. A novel optimization technique based on interpolation theory is
      applied to detect the location of the whole spine in the 3-D image and, using the
      obtained location of the whole spine, to further detect the location of
      individual vertebrae within the spinal column. The obtained vertebra detection
      results represent a robust and accurate initialization for the subsequent
      segmentation of individual vertebrae, which is performed by an improved shape
      constrained deformable model approach. The framework was evaluated on two
      publicly available CT spine image databases of 50 lumbar and 170 thoracolumbar
      vertebrae. Quantitative comparison against corresponding reference vertebra
      segmentations yielded an overall mean centroid-to-centroid distance of 1.1 mm and
      Dice coefficient of 83.6% for vertebra detection, and an overall mean symmetric
      surface distance of 0.3 mm and Dice coefficient of 94.6% for vertebra
      segmentation. The results indicate that by applying the proposed automated
      detection and segmentation framework, vertebrae can be successfully detected and
      accurately segmented in 3-D from CT spine images. 

PMID- 25585416
TI  - Comparing noisy patches for image denoising: a double noise similarity model.
AB  - This paper presents a concept of noise similarity (NS), which can be used to
      refine the comparison of noisy patch and enhance the denoising power of the
      nonlocal means (NLM) filter. The fact behind this concept is that the similarity
      of noisy patch should depend on not only the underlying signal (noise free
      patches), but also the noise. Based on the concept of noise similarity, we
      derived a double NS (DNS) model, which converts the denoising problem into the
      problem of reducing two kinds of noise: one is the superimposed additive noise;
      the other is the deviation error, defined as another kind of noise denoting the
      difference between similar pixels on their true intensities. The former
      corresponds to noise suppression, while the latter corresponds to the restoration
      of image details. To evaluate the effectiveness of the DNS model, we proposed an
      iterative version of the NLM filter, where the two noise similarities can work
      collaboratively in the framework of maximum a posterior. Finally, the
      experimental results demonstrate that the proposed approach can provide
      competitive performance when compared with other state-of-the-art NLM filters.

PMID- 25585417
TI  - Enhanced figure-ground classification with background prior propagation.
AB  - We present an adaptive figure-ground segmentation algorithm that is capable of
      extracting foreground objects in a generic environment. Starting from an
      interactively assigned background mask, an initial background prior is defined
      and multiple soft-label partitions are generated from different foreground priors
      by progressive patch merging. These partitions are fused to produce a foreground
      probability map. The probability map is then binarized via threshold sweeping to
      create multiple hard-label candidates. A set of segmentation hypotheses is formed
      using different evaluation scores. From this set, the hypothesis with maximal
      local stability is propagated as the new background prior, and the segmentation
      process is repeated until convergence. Similarity voting is used to select a
      winner set, and the corresponding hypotheses are fused to yield the final
      segmentation result. Experiments indicate that our method performs at or above
      the current state-of-the-art on several data sets, with particular success on
      challenging scenes that contain irregular or multiple-connected foregrounds.

PMID- 25585418
TI  - The guided bilateral filter: when the joint/cross bilateral filter becomes
      robust.
AB  - The bilateral filter and its variants, such as the joint/cross bilateral filter,
      are well-known edge-preserving image smoothing tools used in many applications.
      The reason of this success is its simple definition and the possibility of many
      adaptations. The bilateral filter is known to be related to robust estimation.
      This link is lost by the ad hoc introduction of the guide image in the
      joint/cross bilateral filter. We here propose a new way to derive the joint/cross
      bilateral filter as a particular case of a more generic filter, which we name the
      guided bilateral filter. This new filter is iterative, generic, inherits the
      robustness properties of the robust bilateral filter, and uses a guide image. The
      link with robust estimation allows us to relate the filter parameters with the
      statistics of input images. A scheme based on graduated nonconvexity is proposed,
      which allows converging to an interesting local minimum even when the cost
      function is nonconvex. With this scheme, the guided bilateral filter can handle
      non-Gaussian noise on the image to be filtered. A complementary scheme is also
      proposed to handle non-Gaussian noise on the guide image even if both are
      strongly correlated. This allows the guided bilateral filter to handle situations
      with more noise than the joint/cross bilateral filter can work with and leads to
      high peak signal-to-noise ratio values as shown experimentally. 

PMID- 25585419
TI  - An improved joint optimization of multiple level set functions for the
      segmentation of overlapping cervical cells.
AB  - In this paper, we present an improved algorithm for the segmentation of cytoplasm
      and nuclei from clumps of overlapping cervical cells. This problem is notoriously
      difficult because of the degree of overlap among cells, the poor contrast of cell
      cytoplasm and the presence of mucus, blood, and inflammatory cells. Our
      methodology addresses these issues by utilizing a joint optimization of multiple
      level set functions, where each function represents a cell within a clump, that
      have both unary (intracell) and pairwise (intercell) constraints. The unary
      constraints are based on contour length, edge strength, and cell shape, while the
      pairwise constraint is computed based on the area of the overlapping regions. In
      this way, our methodology enables the analysis of nuclei and cytoplasm from both
      free-lying and overlapping cells. We provide a systematic evaluation of our
      methodology using a database of over 900 images generated by synthetically
      overlapping images of free-lying cervical cells, where the number of cells within
      a clump is varied from 2 to 10 and the overlap coefficient between pairs of cells
      from 0.1 to 0.5. This quantitative assessment demonstrates that our methodology
      can successfully segment clumps of up to 10 cells, provided the overlap between
      pairs of cells is <;0.2. Moreover, if the clump consists of three or fewer cells,
      then our methodology can successfully segment individual cells even when the
      overlap is ~0.5. We also evaluate our approach quantitatively and qualitatively
      on a set of 16 extended depth of field images, where we are able to segment a
      total of 645 cells, of which only ~10% are free-lying. Finally, we demonstrate
      that our method of cell nuclei segmentation is competitive when compared with the
      current state of the art. 

PMID- 25585420
TI  - BSIFT: toward data-independent codebook for large scale image search.
AB  - Bag-of-Words (BoWs) model based on Scale Invariant Feature Transform (SIFT) has
      been widely used in large-scale image retrieval applications. Feature
      quantization by vector quantization plays a crucial role in BoW model, which
      generates visual words from the high- dimensional SIFT features, so as to adapt
      to the inverted file structure for the scalable retrieval. Traditional feature
      quantization approaches suffer several issues, such as necessity of visual
      codebook training, limited reliability, and update inefficiency. To avoid the
      above problems, in this paper, a novel feature quantization scheme is proposed to
      efficiently quantize each SIFT descriptor to a descriptive and discriminative bit
      vector, which is called binary SIFT (BSIFT). Our quantizer is independent of
      image collections. In addition, by taking the first 32 bits out from BSIFT as
      code word, the generated BSIFT naturally lends itself to adapt to the classic
      inverted file structure for image indexing. Moreover, the quantization error is
      reduced by feature filtering, code word expansion, and query sensitive mask
      shielding. Without any explicit codebook for quantization, our approach can be
      readily applied in image search in some resource-limited scenarios. We evaluate
      the proposed algorithm for large scale image search on two public image data
      sets. Experimental results demonstrate the index efficiency and retrieval
      accuracy of our approach.

PMID- 25585421
TI  - 2D discrete Fourier transform on sliding windows.
AB  - Discrete Fourier transform (DFT) is the most widely used method for determining
      the frequency spectra of digital signals. In this paper, a 2D sliding DFT (2D
      SDFT) algorithm is proposed for fast implementation of the DFT on 2D sliding
      windows. The proposed 2D SDFT algorithm directly computes the DFT bins of the
      current window using the precalculated bins of the previous window. Since the
      proposed algorithm is designed to accelerate the sliding transform process of a
      2D input signal, it can be directly applied to computer vision and image
      processing applications. The theoretical analysis shows that the computational
      requirement of the proposed 2D SDFT algorithm is the lowest among existing 2D DFT
      algorithms. Moreover, the output of the 2D SDFT is mathematically equivalent to
      that of the traditional DFT at all pixel positions.

PMID- 25585422
TI  - Ranks for pairs of spatial fields via metric based on grayscale morphological
      distances.
AB  - Based on a set of morphological distances computed between the grayscale images
      (spatial fields) of similar size specifications, the ratios of selected
      morphological distances, and the ratios of areas of infima and suprema of
      grayscale images, a new metric to quantify the degree of similarity between the
      grayscale images is proposed. We denote the two spatial fields (grayscale
      images), respectively, with f(i) and f(j), and the infima and suprema of these
      spatial fields with (f(i)?f(j)) and ( f(i)?f(j)). The three morphology-based
      distances include: 1) dilation distance d( f(i),f(j)) ; 2) erosion distance e(
      f(i),f(j)); and 3) median-based distance MN ( f(i),f(j)) . By employing these
      parameters, which play vital role in construction of parameter-specific
      interaction matrices, we provide a metric to designate every possible pair of
      images that can be considered out of a database consisting of a huge number of
      images. We demonstrate the whole approach on: 1) synthetic spatial fields; 2) a
      set of 12 similar-sized grayscale images representing cloud-top temperatures of a
      specific region for 12 different time instants; and 3) four spatial elevation
      fields to rank possible pairs of images.

PMID- 25585423
TI  - On antiforensic concealability with rate-distortion tradeoff.
AB  - A signal's compression history is of particular forensic significance because it
      contains important information about the origin and authenticity of a signal.
      Because of this, antiforensic techniques have been developed that allow a forger
      to conceal manipulation fingerprints. However, when antiforensic techniques are
      applied to multimedia content, distortion maybe introduced, or the data size may
      be increased. Furthermore,when compressing an antiforensically modified forgery,
      a tradeoff between the rate and distortion is introduced into the system. As a
      result, a forger must balance three factors, such as how much the fingerprints
      can be forensically concealed, the data rate, and the distortion, are
      interrelated to form a 3D tradeoff. In this paper, we characterize this tradeoff
      by defining concealability and using it to measure the effectiveness of an
      antiforensic attack. Then, to demonstrate this tradeoff in a realistic scenario,
      we examine the concealability-rate-distortion tradeoff in double JPEG compression
      antiforensics. To evaluate this tradeoff, we propose flexible antiforensic dither
      as an attack in which the forger can vary the strength of antiforensics. To
      reduce the time and computational complexity associated with decoding a JPEG
      file, applying antiforensics, and recompressing, we propose anantiforensic
      transcoder to efficiently complete these tasks in one step. Through simulation,
      two surprising results are revealed. One is that if a forger uses a lower quality
      factor in the second compression, applying antiforensics can both increase
      concealability and decrease the data rate. The other is that for any pairing of
      concealability and distortion values, achieved using a higher secondary quality
      factor, can also be achieved using a lower secondary quality factor at a lower
      data rate. As a result, the forger has an incentive to always recompress using a
      lower secondary quality factor.

PMID- 25585424
TI  - Interactive segmentation and visualization of DTI data using a hierarchical
      watershed representation.
AB  - Magnetic resonance diffusion tensor imaging (DTI) measures diffusion of water
      molecules and is used to characterize orientation of white matter fibers and
      connectivity of neurological structures. Segmentation and visualization of DT
      images is challenging, because of low data quality and complexity of anatomical
      structures. In this paper, we propose an interactive segmentation approach, based
      on a hierarchical representation of the input DT image through a tree structure.
      The tree is obtained by successively merging watershed regions, based on the
      morphological waterfall approach, hence the name watershed tree. Region merging
      is done according to a combined similarity and homogeneity criterion. We
      introduce filters that work on the proposed tree representation, and that enable
      region-based attribute filtering of DTI data. Linked views between the
      visualizations of the simplified DT image and the tree enable a user to visually
      explore both data and tree at interactive rates. The coupling of filtering,
      semiautomatic segmentation by labeling nodes in the tree, and various interaction
      mechanisms support the segmentation task. Our method is robust against noise,
      which we demonstrate on synthetic and real DTI data.

PMID- 25585425
TI  - A wearable neuro-feedback system with EEG-based mental status monitoring and
      transcranial electrical stimulation.
AB  - A wearable neuro-feedback system is proposed with a low-power neuro-feedback SoC
      (NFS), which supports mental status monitoring with encephalography (EEG) and
      transcranial electrical stimulation (tES) for neuro-modulation. Self-configured
      independent component analysis (ICA) is implemented to accelerate source
      separation at low power. Moreover, an embedded support vector machine (SVM)
      enables online source classification, configuring the ICA accelerator adaptively
      depending on the types of the decomposed components. Owing to the hardwired
      accelerating functions, the NFS dissipates only 4.45 mW to yield 16 independent
      components. For non-invasive neuro-modulation, tES stimulation up to 2 mA is
      implemented on the SoC. The NFS is fabricated in 130-nm CMOS technology. 

PMID- 25585426
TI  - Nuclear norm-based 2-DPCA for extracting features from images.
AB  - The 2-D principal component analysis (2-DPCA) is a widely used method for image
      feature extraction. However, it can be equivalently implemented via image-row
      based principal component analysis. This paper presents a structured 2-D method
      called nuclear norm-based 2-DPCA (N-2-DPCA), which uses a nuclear norm-based
      reconstruction error criterion. The nuclear norm is a matrix norm, which can
      provide a structured 2-D characterization for the reconstruction error image. The
      reconstruction error criterion is minimized by converting the nuclear norm-based
      optimization problem into a series of F-norm-based optimization problems. In
      addition, N-2-DPCA is extended to a bilateral projection-based N-2-DPCA (N-B2
      DPCA). The virtue of N-B2-DPCA over N-2-DPCA is that an image can be represented
      with fewer coefficients. N-2-DPCA and N-B2-DPCA are applied to face recognition
      and reconstruction and evaluated using the Extended Yale B, CMU PIE, FRGC, and AR
      databases. Experimental results demonstrate the effectiveness of the proposed
      methods. 

PMID- 25585427
TI  - Optimal critic learning for robot control in time-varying environments.
AB  - In this paper, optimal critic learning is developed for robot control in a time
      varying environment. The unknown environment is described as a linear system with
      time-varying parameters, and impedance control is employed for the interaction
      control. Desired impedance parameters are obtained in the sense of an optimal
      realization of the composite of trajectory tracking and force regulation. Q 
      function-based critic learning is developed to determine the optimal impedance
      parameters without the knowledge of the system dynamics. The simulation results
      are presented and compared with existing methods, and the efficacy of the
      proposed method is verified. 

PMID- 25585428
TI  - A parametric classification rule based on the exponentially embedded family.
AB  - In this paper, we extend the exponentially embedded family (EEF), a new approach
      to model order estimation and probability density function construction
      originally proposed by Kay in 2005, to multivariate pattern recognition.
      Specifically, a parametric classifier rule based on the EEF is developed, in
      which we construct a distribution for each class based on a reference
      distribution. The proposed method can address different types of classification
      problems in either a data-driven manner or a model-driven manner. In this paper,
      we demonstrate its effectiveness with examples of synthetic data classification
      and real-life data classification in a data-driven manner and the example of
      power quality disturbance classification in a model-driven manner. To evaluate
      the classification performance of our approach, the Monte-Carlo method is used in
      our experiments. The promising experimental results indicate many potential
      applications of the proposed method. 

PMID- 25585429
TI  - A Novel Approach to Segment Skin Lesions in Dermoscopic Images Based on a
      Deformable Model.
AB  - Dermoscopy is an imaging technique that has been widely used in the diagnosis of
      skin lesions. However, its accuracy largely depends on the dermatologist's
      experience; thus, computer-aided diagnosis techniques are required. In this
      paper, a novel approach based on a deformable model is proposed to handle the
      segmentation of skin lesions in dermoscopic images. The RGB color space is
      converted so that the color information contained in the images can be used
      effectively to differentiate normal skin and skin lesions; and the differences in
      the color channels are combined together to define the speed function and the
      stopping criterion of the deformable model. This novel approach is robust against
      the noise, and provides an effective and flexible segmentation. Two image
      databases were used to test the performance of the novel approach and the
      segmentation results obtained were satisfactory. Quantitative analysis on 250
      dermoscopic images showed that the novel algorithm outperformed other state-of
      the-art algorithms. Also, using comparative data, the reliability and the
      implementation issues of the approach are discussed in this paper. 

PMID- 25585430
TI  - Event-Triggered State Estimation for Complex Networks With Mixed Time Delays via
      Sampled Data Information: The Continuous-Time Case.
AB  - In this paper, the event-triggered state estimation problem is investigated for a
      class of complex networks with mixed time delays using sampled data information.
      A novel state estimator is presented to estimate the network states. A new event
      triggered transmission scheme is proposed to reduce unnecessary network traffic
      between the sensors and the estimator, where the sampled data is transmitted to
      the estimator only when the so-called "event-triggered condition" is satisfied.
      The purpose of the problem addressed is to design an estimator for the complex
      network such that the estimation error is ultimately bounded in mean square. By
      utilizing Lyapunov theory combined with the stochastic analysis approach,
      sufficient conditions are established to guarantee the ultimate boundedness of
      the estimation error in mean square. Then, the desired estimator gain matrices
      are obtained via solving a convex problem. Finally, a numerical example is given
      to illustrate the effectiveness of the results. 

PMID- 25585431
TI  - [Ten-years records of organic arsenic (diphenylarsinic acid) poisoning:
      epidemiology, clinical feature, metabolism, and toxicity].
AB  - We report here the symptoms of diphenylarsinic acid (DPAA) poisoning recorded
      over 10 years since the DPAA contamination of the potable well water was first
      detected in the Kamisu City, Ibaraki Prefecture, in 2003. The poisoning symptoms
      associated with the cerebellum and brainstem included nystagmus, tremors,
      myoclonus, and cerebellar ataxia as well as the symptoms associated with the
      temporal and occipital lobes such as memory impairment, sleep disorder, and
      visual disturbance. Some of the affected children exhibited mental retardation.
      Moreover, reduced blood flow and reduced glucose metabolism in the cerebella,
      brainstem, and temporal and occipital lobes persisted for several years among the
      DPAA-exposed persons. Based on the animal studies for DPAA intoxication, the
      target organs for the DPAA toxicity were determined to be the central nervous
      system (CNS), liver, and biliary system. In particular, DPAA tends to persist in
      the brain for a long time, resulting in long-term impacts on the brain. The
      cerebral blood flow and brain glucose metabolism, which can be measured by
      positron emission tomography (PET) and single photon emission computed tomography
      (SPECT), respectively, are useful objective clinical markers to determine the
      effect of DPAA on CNS. We believe that continuous monitoring of the DPAA-exposed
      people may promote the effect of carcinogen and accelerate brain aging.

PMID- 25585432
TI  - [Carbon monoxide poisoning: clinical features of the victims of the explosion
      accident of Mitsui-Miike Mikawa coal mine 50 years ago].
AB  - Clinical features of carbon monoxide poisoning have been described in 24 victims
      of an intense explosion accident of the Mitsui-Miike Mikawa coal mine in Japan 50
      years ago; these victims were admitted to the Kyushu University Hospital as they
      suffered from severe poisoning. In the early stage of poisoning, all victims
      showed disturbed state of consciousness, varying in duration from 5.5 hours to 3
      months, and the duration of unconsciousness was closely correlated to the
      clinical severity in the late stage. Some of the severely poisoned patients
      showed a transient stage of apallic syndrome. After recovery from
      unconsciousness, all patients presented with severe amnestic syndrome and loss of
      initiative. Neurologically, the extrapyramidal signs were prominent in the early
      stage, which gradually improved in the late stage. Variable types of agnosia and
      apraxia were apparent in some of the severely and moderately poisoned patients in
      the late stage, with prominent Gerstmann syndrome and visual-visuospatial
      agnosias. Since these signs showed poor improvement, the agnosia and apraxia, as
      well as impaired intellectual ability, remained as a sequela of the poisoning,
      and were one of the major causes of deficits of the patients in their daily life
      activities in the late stage.

PMID- 25585433
TI  - [Clinical aspects of the Niigata Minamata disease].
AB  - The Minamata disease was discovered in the Minamata region, Kumamoto Prefecture,
      Japan, in 1956. Symptoms of this disease included cerebellar ataxia, sensory
      disturbance, narrowing of the visual field, and hearing and speech disturbances.
      In 1965, similar conditions were identified in persons living around the Agano
      River area, Niigata Prefecture, Japan and accordingly termed as the Niigata
      Minamata disease or the second Minamata disease. Both the diseases have been
      attributed to poisoning with methyl mercury that was generated during the
      production of acetaldehyde using mercury as a catalyst. The discharged methyl
      mercury accumulated in fishes and shellfishes and caused poisoning on
      consumption. This review discusses the history, clinical presentation including
      atypical forms, and autopsy findings of the Niigata Minamata disease. In
      addition, it highlights the problems about criteria for official recognition and
      the therapeutic trial for this disease.

PMID- 25585434
TI  - [Neurotoxicology of pesticides].
AB  - Pesticides have been used for many years for preventing, destroying, repelling,
      or mitigating pests such as insects, rodents, and weeds. However, most pesticides
      are not completely specific for pests and can also induce damage to the human
      nervous system. In particular, insecticides often directly targets the nervous
      system by affecting major targets such as the neuro-transmitter metabolism,
      neuronal receptors, and ion channels; acetylcholine (ACh) esterase for organo
      phosphates and carbamates, nicotinic ACh receptor for neonicotinoids, gamma
      aminobutyric acid receptors/chloride channels for organochlorides and fipronil,
      and voltage-gated sodium channel for pyrethroids. Additional targets include
      sites in the sodium channels, glutamate-gated chloride channels, and octopamine
      and ryanodine receptors. Several pesticides also produce adverse neurological
      effects indirectly by disrupting the general cellular mechanisms that support the
      high metabolic activity of the nervous system. Nowadays, more potent pesticides
      are being developed as replacements for the older, harmful ones. Pesticide
      neurotoxicity in humans may involve the central or peripheral nervous system or
      both and may induce typical neuronal damage in case of acute poisoning even by
      new agents. However, whether effect of exposure to pesticides at below acute
      poisoning threshold level remains unclear. Moreover, neurotoxicology for
      behavioral and higher-brain function remains an unresolved and a challenging
      problem.

PMID- 25585435
TI  - [SMON: toxicity of clioquinol and the status quo].
AB  - Subacute myelo-optico-neuropathy (SMON) is a disease characterized by subacute
      onset of sensory and motor disorders in the lower half of the body and visual
      impairment preceded by abdominal symptoms. A large number of SMON were observed
      throughout Japan, and the total number of cases reached nearly 10,000 by 1970.
      Despite clinical features mimicking infection or multiple sclerosis, SMON was
      confirmed as being caused by ingestion of clioquinol, an intestinal antibacterial
      drug, based on extensive epidemiological studies. After the governmental ban on
      the use of clioquinol in September 1970, there was a dramatic disappearance of
      new case of SMON. In the 1970s, patients with SMON initiated legal actions
      against the Government and pharmaceutical companies, and the court ruled that the
      settlements would be made as health management allowances and lasting medical
      check-ups. The physical condition of patients with SMON remains severe owing to
      SMON as well as gerontological complications. The pathological findings in
      patients with SMON included symmetrical demyelination in the lateral and
      posterior funiculi of the spinal cord and severe demyelination of the optic nerve
      in patients with blindness. Although clioquinol may show activity against
      Alzheimer's disease or malignancy, its toxic effects cause severe irreversible
      neurological sequelae. Thus, caution must be exercised in the clinical use of
      clioquinol.

PMID- 25585436
TI  - [Neurotoxicity of radiation].
AB  - It is well-known that the central nervous system is thoroughly resistant to
      ionizing radiation as high-dose radiation exposure is required for causing
      neuronal death. In contrast, recent studies have revealed that the hippocampus,
      which could be the main organ involved in disorder of higher brain functions
      after radiation therapy, contains radiation-sensitive cell fractions. In this
      paper, the basics of radiation effects and the molecular mechanism of
      neurotoxicity of radiation have been reviewed and discussed.

PMID- 25585437
TI  - [An antithrombotic therapy from the viewpoint of hematology].
AB  - Platelets and coagulation factors play an important role in the physiological
      process of hemostasis, and are also involved in thrombosis. Treatment strategies
      for thrombosis include antiplatelet and anticoagulant therapies. The former
      approach is effective for managing arterial thrombosis (caused by platelet
      activation), whereas the latter is used to treat venous thrombosis (caused by
      coagulation factor activation). Hemostatic monitoring is crucial for selecting
      the appropriate antithrombotic therapy.

PMID- 25585438
TI  - [Stem cell therapy for dementia].
AB  - Intravenously administrated mesenchymal stem cells (MSCs) isolated and expanded
      from human bone marrow have been reported to ameliorate functional deficits in
      several CNS diseases in both experimental animal models and clinics. Therapeutic
      mechanisms may include replacement of damaged cells, neuroprotective effects,
      induction of axonal sprouting, and neovascularization. Here, we review the
      reparative and protective properties of transplanted MSCs in stroke, describe
      initial clinical studies on intravenous MSC delivery in stroke patients, and
      discuss a perspective on the prospects of MSCs for dementia.

PMID- 25585439
TI  - [Correlation between cognitive impairment and postural instability in patients
      with Parkinson's disease].
AB  - Correlation between frontal-executive function and motor functions, such as gait
      and postural control, has attracted attention in Parkinson's disease (PD).
      However, correlations between other cognitive functional domains and motor
      functions have not been examined. Thus, we examined the correlation between
      different domains of cognitive function and motor functions. Sixty-five PD
      patients were recruited for the present study. Cognitive functions were assessed
      by the 10 subtests of the Neurobehavioral Cognitive Status Examination
      (COGNISTAT). Motor functions were assessed by the Unified Parkinson's Disease
      Rating Scale (UPDRS) as partIII for general motor function and sum of related
      items for tremor, rigidity, bradykinesia, and postural instability. Spearman's
      correlation coefficients between each cognitive and motor assessment were
      compared. Among the 10 subtests of the COGNISTAT, constructions showed
      significant correlation with UPDRS partIII (p<0.01), bradykinesia (p<0.01), and
      postural instability (p<0.001). The latter correlation was stronger than those
      between all motor assessments and both all patients backgrounds and other
      COGNISTAT subtests. In PD patients, postural instability correlates with not only
      frontal executive dysfunctions but also parietal dysfunctions, such as
      visuospatial and constructive impairments. The postural maintenance system is
      suggested to share common physiology with not only frontal-executive function but
      also parietal functions.

PMID- 25585440
TI  - [A case of focal epilepsy manifesting multiple psychiatric auras].
AB  - We present a case of epilepsy with multiple types of focal seizures that were
      misdiagnosed as psychiatric disorders. A 20-year-old female patient presented
      with a variety of episodes, including loss of consciousness, deja vu, fear,
      delusion of possession, violent movements, and generalized convulsions. Each of
      these symptoms appeared in a stereotypic manner. She was initially diagnosed with
      a psychiatric disorder and treated with psychoactive medications, which had no
      effect. Long-term video electroencephalography revealed that her episodes of
      violent movement with impaired consciousness and secondarily generalized seizure
      were epileptic events originating in the right hemisphere. High-field brain
      magnetic resonance imaging for detecting subtle lesions revealed bilateral
      lesions from periventricular nodular heterotopia. Her final diagnosis was right
      hemispheric focal epilepsy. Carbamazepine administration was started, which
      successfully controlled all seizures. The present case demonstrates the pitfall
      of diagnosing focal epilepsy when it presents with multiple types of psychiatric
      aura. Epilepsy should thus be included in differential diagnoses, considering the
      stereotypic nature of symptoms, to avoid misdiagnosis.

PMID- 25585441
TI  - Immunization and Vaccine  related Implementation  Research Advisory Committee 
      (IVIR-AC): summary  of conclusions and  recommendations  17-19 September 2014 
      meeting.

PMID- 25585442
TI  - Complementary and alternative therapies in hospice: The national home and hospice
      care survey: United States, 2007.
AB  - Objective-This report presents national estimates on the provision and use of
      complementary and alternative therapies (CAT) in hospice. Comparisons of
      organizational characteristics of hospice care providers are presented by whether
      the provider offered CAT. Comparisons of selected characteristics of patients
      discharged from hospice are presented by whether they received care from a
      provider that offered CAT, and whether they received a CAT service. Methods
      Estimates are based on data from the 2007 National Home and Hospice Care Survey
      (NHHCS), conducted by the Centers for Disease Control and Prevention's National
      Center for Health Statistics. Results-In 2007, 41.8% of hospice care providers
      offered CAT services, had a CAT provider on staff or under contract, or both.
      Among hospice care providers offering CAT, over one-half offered massage (71.7%),
      supportive group therapy (69.0%), music therapy (62.2%), pet therapy (58.6%), or
      guided imagery or relaxation (52.7%). Of the hospice care providers that offered
      CAT, 21.5% had at least one discharged hospice patient who received CAT during
      hospice care. Overall, 4.9% of all discharged hospice patients received at least
      one CAT from the hospice care provider. Over one-half of discharged patients
      (56.5%) received care from a provider that offered CAT, and of those, 8.6%
      received at least one CAT from the hospice care provider during their stays.
      There were no differences in demographics, health, functional status, or
      admission diagnoses between patients discharged from hospice either by whether
      they received care from a provider that offered CAT or whether they received CAT.

PMID- 25585443
TI  - Anthropometric reference data for children and adults: United States, 2003-2006.
AB  - Objective-This report presents national anthropometric reference data for all
      ages of the U.S. population in 2003-2006, adding to results published previously
      from 1960-2002. Methods-Data are from the National Health and Nutrition
      Examination Survey (NHANES), a complex, stratified, and multistage probability
      sample of the civilian, noninstitutionalized U.S. population. Anthropometry
      measurements were obtained from 19,593 survey participants. The anthropometric
      measures included weight, height, recumbent length, circumferences, limb lengths,
      and skinfold thickness measurements. Results-The tables in this report include
      weighted population means, standard errors of the means, and selected percentiles
      of body measurement values. Because measurements varied by sex and age (as well
      as race and ethnicity in adults), results are reported by these subgroups.
      Conclusions-These latest NHANES data add to the knowledge about trends in child
      growth and development and trends in the distribution of body measurements, such
      as weight and height, in the U.S. population .

PMID- 25585444
TI  - Critical congenital heart disease screening tools may reduce neonatal deaths.

PMID- 25585445
TI  - RP First Look: New recommended practices for surgical attire.

PMID- 25585446
TI  - Understanding ICD-10 and its effect on patient care.

PMID- 25585447
TI  - Former OR Manager of the Year directs team at Nebraska biocontainment unit.

PMID- 25585448
TI  - Software orients staff, advances 'rep-less' model.

PMID- 25585449
TI  - Orthopedic implant overhaul nets cost savings and surgeon satisfaction.

PMID- 25585450
TI  - Potential rewards justify efforts to create bundled payment programs.

PMID- 25585451
TI  - Best sterile processing managers anticipate, collaborate, stay up to date.

PMID- 25585452
TI  - Avera McKennan finds innovative strategies to address orthopedic pain management.

PMID- 25585453
TI  - Conference equips OR leaders with critical management skills.

PMID- 25585454
TI  - Business manager role evolving with challenging times.

PMID- 25585455
TI  - Staff vacation gridlock eased by innovative allocation system.

PMID- 25585457
TI  - Co-management agreements thrive in a culture of responsibility.

PMID- 25585456
TI  - Former pilot applies aviation skills to perioperative nursing.

PMID- 25585458
TI  - Awareness during anesthesia: a rare but disturbing complication.

PMID- 25585459
TI  - Focused competencies give anesthesia technicians a leg up on the efficiency
      ladder.

PMID- 25585460
TI  - Are you in the future of NCF?

PMID- 25585461
TI  - Chaos at work?

PMID- 25585462
TI  - Comprehensive care: looking beyond the presenting problem.

PMID- 25585463
TI  - The most difficult decisions for the most vulnerable patients.

PMID- 25585465
TI  - Being the minority: Christian healthcare professionals in The Netherlands.
AB  - In many societies, spirituality is no longer specifically religious or affiliated
      in a traditional sense. This is especially true in The Netherlands. This study
      examined the qualities of Dutch Christian healthcare professionals, opportunities
      and threats to being Christian, and their perceived need for support to be
      Christian. Respondents (N = 672) had a highly homogeneous picture of the
      qualities, opportunities, and challenges of living out faith at work. However,
      they do not think they have the qualities or opportunities to be overtly
      Christian and would like support to be more explicit in their faith.

PMID- 25585466
TI  - Essential nursing: lessons from the infusion room.
AB  - A patient's long-term experience receiving infusions on an outpatient basis for a
      serious illess leads him to understand and share insights about the essence of
      excellent, compassionate nursing care.

PMID- 25585464
TI  - Supporting families in neonatal loss: relationship and faith key to comfort.
AB  - Around 20,000 neonatal deaths occur each year, many from congenital heart defects
      such as hypoplastic left heart syndrome. Nurses are on the frontline of caring
      for families experiencing neonatal loss. Careful spiritual and cultural
      assessment, attention to beliefs, focusing on relationship, and helping families
      create legacy can assist with grieving and making meaning out of loss.

PMID- 25585467
TI  - Faith community nursing scope of practice: extending access to healthcare.
AB  - The role of the Faith Community Nurse (FCN) is a multifaceted wholistic practice
      focused on individuals, families, and the faith and broader communities. The FCN
      is skilled in professional nursing and spiritual care, supporting health through
      attention to spiritual, physical, mental, and social health. FCNs can help meet
      the growing need for healthcare, especially for the uninsured, poor, and
      homeless. The contribution of FCNs on, primary prevention, health maintenance,
      and management of chronic disease deserves attention to help broaden
      understanding of the scope of FCN practice.

PMID- 25585468
TI  - Tipping the scales on obesity: church-based health promotion for African American
      women.
AB  - Research suggests that over 80% of U.S. adult African American (AA) women are at
      risk for hypertension, cardiovascular disease, and diabetes. In 2011-2012, 56.6%
      of non-Hispanic Black women were obese (BMI >= 30 kg/m2). Project TEACH-
      Transforming, Empowering, and Affecting Congregation Health was designed to
      determine the effectiveness of a faith-based, culturally competent, nutrition and
      exercise program targeting AA women in a church setting.

PMID- 25585469
TI  - Hospice clinical experiences for nursing students: living to the fullest.
AB  - Preparing future nurses to provide appropriate care for patients and their
      families at the end of life can be a formidable challenge for nurse educators.
      Most nursing schools thread end-of-life concepts throughout the curriculum. Grand
      Canyon University includes a 40-hour hospice clinical as a component of a home
      healthcare practicum. Students' weekly written reflections reveal the depth of
      affective learning that occurs during this experience. Article includes hospice
      materials and resources.

PMID- 25585470
TI  - Dealing with academic dishonesty: a redemptive approach.
AB  - Studies reveal that as many as 80% of college students cheat; over half do not
      think cheating is a serious transgression. Developing integrity in nursing
      students is crucial, as their later actions impact patients' lives. How can
      educators foster academic integrity? Two educators from a Christian university
      relay how they approached a student's cheating and the transformative lessons
      they learned.

PMID- 25585471
TI  - Does attitude play a role in spiritual care?

PMID- 25585472
TI  - Can nurse educators be missionaries?

PMID- 25585473
TI  - The power of prayer.

PMID- 25585474
TI  - Police resiliency: an integration of individual and organization.

PMID- 25585475
TI  - Medicine: 30 years after the death of the great humanist.

PMID- 25585476
TI  - Selling through "reflections": mirror neurons and anthropomorphic advertisements.

PMID- 25585477
TI  - Mindfulness in teaching resilience to mental health providers.

PMID- 25585478
TI  - Awareness integration: a new therapeutic model.
AB  - Awareness Integration (AI) is a new model in the field of psychotherapy which
      synthesizes numerous concepts from cognitive, behavioral, emotional, and body
      mind theories. AI aims to enhance self-awareness, increase self-esteem, release
      past traumas and psychological blocks, reduce symptoms of anxiety and depression,
      and promote a clear, realistic, and positive attitude in order to learn and
      implement new skills for an effective, productive, and functional life. This
      model allows for release and then integration through flexibly structured
      questions and expansive interventions that connect core beliefs, emotions,
      locations in the body where emotions are stored and relevant/original memories. A
      pilot study indicated a 76% decrease in depression, a 60% decrease in anxiety, a
      43% increase in self-esteem, and a 20% increase in self-efficacy after taking
      part in AI therapy.

PMID- 25585479
TI  - Horticultural therapy as a measure for recovery support of regional community in
      the disaster area: a preliminary experiment for forty five women who living
      certain region in the coastal area of Miyagi Prefecture.
AB  - Three years have passed since the earthquake, in the coastal areas in the
      disaster area, by population transfer or the like from the temporary housing, the
      importance of the regeneration and revitalization of the local community has been
      pointed out. This study performed a preliminary study to aim at the psychological
      inspection about an effect of the horticultural therapy as the means of the local
      community reproduction support of the disaster area. Forty five women who are
      living in the coastal area of Miyagi Prefecture participated in this study. They
      experienced the Great East Japan earthquake in 2011 and suffered some kind of
      damage caused by the earthquake. The participants were assigned to two groups,
      the intervention group and the control group, via a random draw using a computer.
      The HI group attended the horticultural therapy intervention (HT intervention)
      sessions for 16 weeks. The HT intervention was designed in collaboration with a
      horticultural therapist and clinical psychologists. This intervention comprised a
      total of 16 weekly sessions (120 min each) at the community center and 15 minutes
      per day at participants' homes. We used five psychological measures for an
      intervention evaluation. The HI group showed a significant increase in post-
      intervention SCI-2 total scores, post- intervention SCI-2 membership scores, post
      intervention SCI-2 influence scores, post- intervention SCI-2 meeting needs
      scores, post- intervention SCI-2 shared emotional connection scores, and post-
      intervention RSES score. We believe that these results suggest the effectiveness
      of the horticultural therapy as the means of the local community reproduction.

PMID- 25585480
TI  - Workplace violence in emergency department and its effects on emergency staff.
AB  - Workplace violence (WPV) is a growing problem for healthcare providers,
      particularly for those in the Emergency department (ED), with its increasing
      frequency and severity. Characteristics of WPV are similar in different parts of
      the World with different sociocultural and economic status. As this problem
      remains unsolved, its unwanted effects on mental and physical health of staff
      become more problematic. The most common psychological affects are reduced job
      satisfaction and fear. When the reasons of WPV are investigated; lack of
      preventive policies, educational inadequacy, unwillingness to report assaults as
      a result of a consideration of violence as a routine by the staff and unmet
      expectations of patients and their family may be listed. In the short-term,
      increasing the number of security personnel, flagging the names of the patients
      with a potential of aggression in the computer system and reducing length of stay
      in the ED are measures to implement immediately. In the long-term, governments
      must focus on this subject and develop necessary policies including educational
      programmes in order to reduce WP, before it is too late for another ED worker.

PMID- 25585481
TI  - Multi-natural disasters in Gonaives Haiti: long-term outcomes among child and
      adolescents and social support.
AB  - In this article, we posit the hypothesis that the January 2010 earthquake in Port
      au-Prince reawakened a number of traumas linked to the natural disasters that
      struck Gonaives in 2004 and 2008. The study set out to evaluate the PTSD and
      social support in the affected areas in Gonaives seven years after the disasters.
      The study covered a sample of 917 participants, of whom 534 (58.23%) were
      females, aged between 10 and 23 with an average age of 16.03 (SD = 2.65). A
      variety of scales were used: the Clinician Administered PTSD Scale (CAPS-1); the
      Traumatic Exposure Severity Scale (TESS); the PTSD Check-List Civilian version
      (PCL-C); the Impact of Event Scale Revised (IES-R) and the Social Support
      Questionnaire (SSQ). The results reveal a higher rate of PTSD among the oldest
      participants, a similarly higher rate of social support among Catholics than
      among Protestants, a more severe rate of PTSD among school going children and a
      positive correlation between social support and PTSD.

PMID- 25585482
TI  - Does marriage explain murders in a society? In what way is divorce a public
      health concern?
AB  - INTRODUCTION: Like medicine, public health practitioners seek to understand
      causes of mortality, practices of humans and issues that can change population
      conditions, in order to preserve and care for life. The murder pandemic has been
      such in Jamaica that the World Bank sponsored a qualitative study on crime in
      urban areas in Jamaica in the late 1990s to provide a platform to guide policy
      intervention and programmes. As a result this study will fill the gap in the
      literature by providing the evidence to support that divorce and marriage are
      public health concerns from the perspective of murders. OBJECTIVE: To evaluate
      the role of divorce and marital relationships on murders. MATERIALS AND METHODS:
      The data for this study are taken from various Jamaica Government Publications.
      The period for this work is from 1950 through 2013. Data were recorded, stored
      and retrieved using the Statistical Packages for the Social Sciences (SPSS) for
      Windows, Version 21.0. The level of significance that is used to determine
      statistical significance is less than 5% (0.05). Ordinary least square (OLS)
      regression analyses and curve estimations were used to determine models and best
      fitted models. RESULTS: On average, annually, 523 Jamaicans are murdered (+/-
      484), with there being 9,531 marriages (+/- 22,747) and 904 divorces (+/- 468).
      Logged marriage rate and divorce rate are factors of murder rate, with both
      independent factors accounting for 82.2% of the variability in the murder rate.
      Both factors are positively correlated with the murder rate, with the divorce
      rate accounting for most of the variance in the murder rate (R2 = 79.2%).
      CONCLUSION: Death can be extremely devasting to families, however, murder among
      married couples can severely disrupt the lives of both families along with any
      children from such relationship.

PMID- 25585483
TI  - The role of diffusion weighted MR imaging in the diagnosis of acute pancreatitis.
AB  - OBJECTIVE: To understand the utility of Diffusion-weighted MR imaging (DWI) in
      the diagnosis of acute pancreatitis. CONCLUSION: DWI can analyse the major
      manifestations of acute pancreatitis without any contrast agent use and may
      replace Abdominal CT and routine Pancreas MRI as a primary investigation tool for
      acute pancreatitis.

PMID- 25585484
TI  - A longitudinal study of posttraumatic stress symptoms and their predictors in
      rescue workers after a firework factory disaster.
AB  - INTRODUCTION: This is a follow up study on rescue workers participating in the
      primary rescue during and immediately after the explosion of a firework factory.
      We aimed to estimate the possible PTSD prevalence at five and 18 months post
      disaster, determining if the level of PTSD symptoms at 18 months could be
      predicted from factors measured at five months. METHODS: We included measures of
      posttraumatic symptoms, social support, locus of control and demographic
      questions. RESULTS: The possible PTSD prevalence rose from 1.6% (n = 465) at five
      months post disaster to 3.1% (n = 130) at 18 months. A hierarchical linear
      regression predicted 59% of PTSD symptoms variance at 18 months post disaster. In
      the final regression, somatization explained the greatest part of the symptom
      variance (42%), followed by locus of control (29%) and major life events prior to
      and right after the disaster (23%). CONCLUSION: Rescue workers seemed to be
      relatively robust to traumatic exposure: The prevalence of possible PTSD in our
      study was even lower than previous studies, probably because of the less severe
      consequences of the disaster studied. Furthermore, we found that PTSD symptom
      level at 18 months post disaster was highly predicted by psychological factors,
      particularly by somatization. However, further investigations of traumatic
      responding are required in this population.

PMID- 25585485
TI  - Why are psychiatric disorders in children becoming more and more common?
AB  - In the last decades, an increase of new paediatric problems requiring medical
      care like eating disorders, behavioural and attention problems has been observed.
      Based on the hypothesis that mental illness is accompanied by autonomic
      dysfunction, we compared measurements of heart rate variability (HRV) in Holter
      ECG's from children with attention deficit/hyperactivity disorder (ADHD) with
      those of healthy children and a historical control from 1997. METHOD: We analysed
      the HRV parameters SDNN, rMSSD and pNN50 from 24 hours Holter ECG from children
      (mean age 10.8 years) with ADHD before or during medical therapy with
      methylphenidate (MPH). These values were compared with aged matched healthy
      children. RESULTS: Compared to healthy controls ADHD children with and without
      MPH treatment showed significantly higher mean heart rates, lower pNN50 and lower
      RMSSD. pNN50 and RMSSD values of healthy children are lower compared to the
      historical control group from 1997. CONCLUSION: Compared to healthy children the
      peak of parasympathic activity measured by the HRV values pNN50 and RMSSD in
      early adolescence was reduced in children with ADHD. Compared to a historical
      control these values are also reduced in healthy children. A reduced vagal
      activity will--within the meaning of W. Porges polyvagal theory--have
      consequences on the social and emotional development of children. Moreover this
      observation may have consequences for an enhanced cardiovascular risk.

PMID- 25585486
TI  - Curbing road traffic accidents--the major cause of facial fractures.

PMID- 25585487
TI  - Ten years of "CHOICES" in Portugal: four generations, a real resilient
      opportunity.
AB  - "Escolhas" ("Choices") is a Portuguese programme that aims to promote children
      and youth social inclusion in deprived socioeconomic contexts. The present study
      aims to identify internal and external resources perceived by children and
      adolescents that participated in the programme, to understand the impact in life
      contexts, and to identify the resources nominated by their family, project
      professionals and partners. A qualitative method was used in order to analyze 365
      discourses from four different groups: children and adolescents (149), family
      (40), project professionals (126) and project partners (50). The model used was
      Benard's Conceptual Model for Resilience and Youth Development. The conclusions
      highlight the success and relevance of Programa Escolhas ("CHOICES") regarding
      the children and the adolescents and their families, by promoting social
      inclusion in deprived socioeconomic contexts.

PMID- 25585488
TI  - Treating veteran posttraumatic stress disorder using the Comprehensive Resource
      Model.
AB  - The Comprehensive Resource Model is a groundbreaking psychotherapeutic treatment
      modality with broad possibilities for use with the military veteran population.
      OBJECTIVE: This article describes a clinical case example where this modality was
      used with a veteran presenting with severe PTSD symptoms. METHOD: Six 60-75
      minute treatment sessions are described. Symptoms were measured before and after
      treatment and at a two-year follow-up using the Posttraumatic Diagnostic Scale,
      Hospital Anxiety and Depression scale, and Clinical Global Impression scale.
      RESULTS: Findings showed that the treatment was effective at relieving symptoms
      of dissociation and flashbacks, even after two years. Some symptoms remained such
      as hypersensitivity to loud noises. CONCLUSION: The Comprehensive Resource Model,
      specifically the Resource Energy Grid, provided a safe, effective way to treat
      some very challenging symptoms. Studies on larger sample sizes would be necessary
      for generalizability. An Appendix by the spouse of the subject provides
      additional support for the findings.

PMID- 25585489
TI  - Mini review: psychosocial stress such as violence against their partners could
      benefit general immunity in intimate partner violence perpetrators.
AB  - Intimate Partner Violence (IPV) perpetrators use physical and/or psychological
      abuse to control their partners and achieve a dominant status. As dominance is
      associated with low disease risk and fast quick illness recovery from an illness,
      such behaviors may contribute to improving their health at the expense of that of
      the battered women. Studies with immunological and hormonal parameters have
      recently revealed that IPV perpetrators present higher general immunocompetence
      (salivary IgA levels) in response to acute stress, especially during the
      preparation/anticipation period and when externalizing their anger. Salivary IgA
      levels have been proved to be increased by hormones, specifically by high
      testosterone and low cortisol characteristic in IPV perpetrators. Moreover, a
      high proneness to express anger (defined by high T/C ratio) supposes an increase
      in self-esteem and mental health. Thus, the use of violence against partners
      could reinforce their dominant status and, consequently, may serve to indirectly
      promote IPV perpetrators' immunity.

PMID- 25585490
TI  - Re-thinking typologies of multiple murders: the missing category of serial-mass
      murder and its theoretical and practical implications.
AB  - The concept of multiple murders (mm) is as old as humanity itself but it has only
      become prevalent in academic thought within the last three decades. Over this
      period scholars have introduced two main attitudes regarding multiple murders.
      Some argue that multiple murders are, theoretically and empirically, one concept
      that includes different sub-types: mass murder, spree murder, and serial murder.
      Other scholars claim that those "sub categories", are a whole different
      phenomenon, which are worthy and needed a separate examination and discussion
      because its uniqueness. To my opinion, this argument is more a semantic one than
      a fundamental one, as long as we consider each type of these murders as a unique
      phenomenon, with its own and unique characteristics. In addition both parties
      agree that the concept of multiple murders is differentiated into the same three
      main sub-categories. My argument is that a fourth sub-category of mm exists which
      goes unrecognized by most scholars. This sub-category, named "serial-mass
      murder," will help to differentiate the sub-categories more accurately and will
      more clearly define each of the remaining sub-categories.

PMID- 25585491
TI  - Trauma in sub-Saharan Africa: review of cost, estimation methods, and
      interventions.
AB  - Trauma is a widely acknowledged problem facing individuals and communities in
      developing countries. In sub-Saharan Africa-a region that is home to some of the
      world's worst human rights violations, ethnic and civil conflicts, disease
      epidemics, and conditions of poverty-trauma is an all-too-common experience in
      citizens' daily lives. In order to address these conditions effectively, the
      impact of trauma must be understood. The authors reviewed recent literature on
      the cost and consequences of psychological trauma in sub-Saharan Africa to
      provide a substantive perspective on how trauma affects individuals, communities,
      and organizations and to inform the effort to determine a method for measuring
      the impact of trauma in sub-Saharan Africa and the efficacy of trauma
      interventions in the region. Several recommendations are offered to help broaden
      and deepen the current approaches to conceptualizing trauma, evaluating its cost,
      and intervening on behalf of those impacted by trauma in sub-Saharan Africa.

PMID- 25585492
TI  - Mai-Mai militia and sexual violence in Democratic Republic of the Congo.
AB  - This article sets the reasons for the brutal violence against women. It focuses
      on three field sites providing insight into Mai-Mai motivations and their
      attitudes toward sexual violence. According to most sources, 5.5 million people
      have died since the beginning of the war in the Democratic Republic of the Congo
      (DRC) in 1994, and rape is used as a weapon of destruction. More than 15,000
      rapes were reported in the DRC in the last year--accounts of these rapes include
      descriptions of horrific acts, such as mutilation and the killing of unborn
      children. The sexual violence is so severe in the DRC that some have described
      rape in the country as the worst in the world. Sexual violence has long lasting
      consequences and far-reaching impacts on individual survivors, their families,
      and their communities in the Democratic Republic of the Congo.

PMID- 25585493
TI  - A search for the phylogenetic relationship of the ascomycete Rhizoctonia
      leguminicola using genetic analysis.
AB  - Rhizoctonia leguminicola, which causes fungal blackpatch disease of legumes and
      other plants, produces slaframine and swainsonine that are largely responsible
      for causing salivation, lacrimation, frequent urination, and diarrhea in grazing
      animals including cattle, sheep, and horses. The original identification of R.
      leguminicola was based only on morphological characters of the fungal mycelia in
      cultures because of the lack of fungal genetic markers. Recent investigations
      suggested that R. leguminicola does not belong to genus Rhizoctonia and is
      instead a member of the ascomycetes, necessitating an accurate reclassification.
      The objective of this study was to use both genetic and morphological characters
      of R. leguminicola to find taxonomic placement of this pathogen within
      ascomycetes. Internal transcribed spacer region (ITS) and glyceraldehyde-3
      phosphate dehydrogenase (gpd) encoding gene were amplified from R. leguminicola
      isolates by PCR using universal primers and sequencing. Rhizoctonia leguminicola
      ITS and gpd sequences were aligned with other fungal sequences of close
      relatives, and phylogenetic trees were constructed using neighbor-joining and
      parsimony analyses. Rhizoctonia leguminicola isolates were clustered within a
      clade that contains several genera of ascomycetes belonging to the class
      dothideomycetes. We suggest that the fungus is misidentified in the genus
      Rhizoctonia and propose its reclassification in a new genus within the phylum
      Ascomycota.

PMID- 25585494
TI  - Combination of double aortic arch and interruption of aortic arch in pulmonary
      atresia with ventricular septal defect.
AB  - No reports on pulmonary atresia with ventricular septal defect with the
      combination of double aortic arch and interruption between left and right carotid
      arteries have been published so far. 

PMID- 25585495
TI  - MicroRNAs are differentially deregulated in mammary malignant phyllodes tumour.
AB  - AIMS: MicroRNAs (miRs) have been shown to play important roles in tumour
      progression. Their expression pattern can be useful for cancer classification.
      However, little is known about miRs in mammary phyllodes tumours (PT). METHODS
      AND RESULTS: In this study, polymerase chain reaction (PCR)-based miR profiling
      was performed in a small PT cohort to identify deregulated miRs in malignant PT.
      The purported roles and targets of these miRs were further validated.
      Unsupervised clustering of miR expression profiling segregated PT into different
      grades, implicating the miR profile in PT classification. Among the deregulated
      miRs, miR-21, miR-335 and miR-155 were validated to be higher in malignant than
      in lower-grade PT in the independent cohort by quantitative PCR (qPCR) (P <=
      0.032). Their expression correlated with some of the malignant histological
      features, including high stromal cellularity, nuclear pleomorphism and mitosis.
      Subsequent analysis of their downstream proteins, namely PTEN for miR-21/miR-155
      and Rb for miR-335, also showed an independent significant negative association
      between miR and protein expression. CONCLUSIONS: Differential expression of miRs
      in PT could be useful in diagnosis and grading of PT. Their deregulated
      expression, together with the altered downstream targets, implicated their active
      involvement in PT malignant transformation.

PMID- 25585496
TI  - Ebola in pregnancy: risk and clinical outcomes.

PMID- 25585497
TI  - The complete mitochondrial genome of the Blue-face angelfish, Pomacanthus
      xanthometapon (Perciformes: Pomacanthidae).
AB  - In this study, the complete mitogenome sequence of the Blue-face angelfish,
      Pomacanthus xanthometapon (Perciformes: Pomacanthidae) has been sequenced by the
      next-generation sequencing method. The assembled mitogenome consisting of 16,533
      bp includes 13 protein coding genes, 22 transfer RNAs, and two ribosomal RNAs
      genes. The overall base composition of Blue-face angelfish is 28.7% for A, 28.9%
      for C, 15.9% for G, 26.6% for T and show 84% identities to flame angelfish
      Centropyge loriculus. The complete mitogenome of the Blue-face angelfish provides
      essential and important DNA molecular data for further phylogeography and
      evolutionary analysis for marine angelfish phylogeny.

PMID- 25585498
TI  - The complete mitochondrial genome of the Emperor angelfish, Pomacanthus imperator
      (Perciformes: Pomacanthidae).
AB  - In this study, the complete mitogenome sequence of the Emperor angelfish,
      Pomacanthus imperator (Perciformes: Pomacanthidae) has been sequenced by the next
      generation sequencing method. The assembled mitogenome consisting of 16,538 bp,
      including 13 protein coding genes, 22 transfer RNAs, and two ribosomal RNAs
      genes. The overall base composition of Emperor angelfish is 28.4% for A, 28.2%
      for C, 16.2% for G, 27.2% for T and show 82% identities to Bluestripe angelfish
      Chaetodontoplus septentrionalis. The complete mitogenome of the Emperor angelfish
      provides essential and important DNA molecular data for further phylogeography
      and evolutionary analysis for marine angelfish phylogeny.

PMID- 25585499
TI  - Imaging and pathologic characteristics of breast amyloidosis.

PMID- 25585501
TI  - Origins of hydration lubrication.
AB  - Why is friction in healthy hips and knees so low? Hydration lubrication,
      according to which hydration shells surrounding charges act as lubricating
      elements in boundary layers (including those coating cartilage in joints), has
      been invoked to account for the extremely low sliding friction between surfaces
      in aqueous media, but not well understood. Here we report the direct
      determination of energy dissipation within such sheared hydration shells. By
      trapping hydrated ions in a 0.4-1 nm gap between atomically smooth charged
      surfaces as they slide past each other, we are able to separate the dissipation
      modes of the friction and, in particular, identify the viscous losses in the
      subnanometre hydration shells. Our results shed light on the origins of hydration
      lubrication, with potential implications both for aqueous boundary lubricants and
      for biolubrication. 

PMID- 25585500
TI  - Perioperative and long-term renal functional outcomes of robotic versus
      laparoscopic partial nephrectomy: a multicenter matched-pair comparison.
AB  - PURPOSE: We compared perioperative and long-term renal functional outcomes of
      robot-assisted partial nephrectomy (RAPN) with laparoscopic partial nephrectomy
      (LPN) for small renal masses. MATERIALS AND METHODS: A total of 1,032 patients
      were included for evaluation; propensity score matching was performed to adjust
      for potential baseline confounders, which resulted in 195 LPNs matched to 195
      RAPNs. Patient characteristics including preoperative estimated glomerular
      filtration rate (eGFR) were investigated, and postoperative results were
      evaluated. RESULTS: No significant differences were found between the groups with
      regard to age, body mass index, sex distribution, preoperative eGFR, or tumor
      size. The mean follow-up period was 32.4 +/- 21.1 months for LPN patients versus
      31.1 +/- 24.5 months for RAPN patients (p = 0.589). Operative time (p < 0.001)
      and warm ischemic time (p < 0.001) were significantly shorter in the RAPN group.
      No significant differences were observed in the overall change in eGFR (p =
      0.768) or positive surgical margin rate (p = 0.653). A multivariate analysis
      showed that preoperative eGFR and hypertension significantly influenced the risk
      of stage 3 and 4 chronic kidney disease. A significant deterioration in renal
      function occurred 3 months after surgery. However, renal function increased
      gradually after the nadir eGFR was reached. The amount of renal functional
      recovery was higher in the RAPN group. CONCLUSIONS: Operative parameters for RAPN
      appear to be less affected by tumor complexity. Functional outcomes of RAPN were
      superior to those of LPN. Renal function recovered continuously during the 60
      month follow-up period after partial nephrectomy.

PMID- 25585502
TI  - Efficacy and safety of intraperitoneal dexmedetomidine with bupivacaine in
      laparoscopic colorectal cancer surgery, a randomized trial.
AB  - OBJECTIVE: Our objective is to investigate the efficacy and safety of
      intraperitoneal dexmedetomidine (Dex) combined with bupivacaine in patients
      undergoing laparoscopic colorectal cancer surgery. DESIGN: Randomized double
      blind study. SETTING: Academic medical center. PATIENTS AND METHODS: Forty-five
      patients scheduled for laparoscopic colorectal cancer surgery were randomly
      assigned for intraperitoneal administration of 50 mL saline (control group; GI, n
      = 15), 50 mL bupivacaine 0.25% (125 mg; GII, n = 15), or 50 mL bupivacaine 0.25%
      (125 mg) +1 MUg/kg Dex (GIII, n = 15). Patients were assessed during the first 24
      hours postoperatively for hemodynamics, visual analogue scale (VAS), time to
      first request of analgesia, total analgesic consumption, shoulder pain, and side
      effects. RESULTS: A significant reduction was observed in VAS in GIII at base
      line, 2, 4, and 24 hours postoperatively in comparison to GI and GII (P < 0.05).
      The time to first analgesic requirement was significantly prolonged in GIII (P <
      0.05). The mean total consumption of rescue analgesia was significantly reduced
      in GIII. CONCLUSION: We conclude that intraperitoneal administration of Dex 1
      MUg/kg combined with bupivacaine improves the quality and the duration of
      postoperative analgesia and provides an analgesic sparing effect compared to
      bupivacaine alone without significant adverse effects in patients undergoing
      laparoscopic colorectal cancer surgery.

PMID- 25585503
TI  - MicroRNA-22-3p is down-regulated in the plasma of Han Chinese patients with
      premature ovarian failure.
AB  - OBJECTIVE: To determine whether plasma microRNAs (miRNAs) are differentially
      expressed between women with and without premature ovarian failure (POF), and to
      uncover the association of miRNAs with risk of POF. DESIGN: Microarray with real
      time polymerase chain reaction validation. SETTING: University hospital.
      PATIENT(S): A total of 140 individuals with premature ovarian failure (POF) and
      140 age- and body mass index-matched control subjects of Han Chinese ancestry.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Relative miRNA expression levels
      in plasma of POF and control group. RESULT(S): Fifty-one differentially expressed
      miRNAs were identified by chip-based discovery stage between ten patients with
      POF and ten control subjects, among which nine miRNAs (let-7b-5p, let-7c, miR-15b
      5p, miR-22-3p, miR-23a-3p, miR-23b-3p, miR-24-3p, miR-151a-5p, and miR-151b) were
      selected and validated. The relative expression level of miR-22-3p was
      significantly down-regulated in POF compared with control subjects. MiR-22-3p
      yielded a receiver operating characteristic (ROC) curve area of 0.668 (95%
      confidence interval 0.602-0.733) in discriminating POF from controls. In
      addition, logistic binary regression analysis and linear regression analysis
      showed the miR-22-3p to be a protective factor for POF (odds ratio 0.766, 95% CI
      0.643-0.912) and negatively associated with serum FSH. Furthermore,
      bioinformatics analysis indicated that the target function of miR-22-3p was
      involved in apoptosis, endocytosis, and tumorigenesis. CONCLUSION(S): Mir-22-3p
      showed a lower expression level in POF and was modestly effective in
      distinguishing POF from control subjects. The decreased expression of miR-22-3p
      in plasma of POF may reflect the diminished ovarian reserve and be a consequence
      of the pathologic process of POF.

PMID- 25585504
TI  - Influence of adrenal hyperandrogenism on the clinical and metabolic phenotype of
      women with polycystic ovary syndrome.
AB  - OBJECTIVE: To study the impact of adrenal hyperandrogenism (AH; defined as DHEAS
      concentration >95th percentile of a healthy female control population) on
      cardiometabolic risk factors associated with polycystic ovary syndrome (PCOS).
      DESIGN: Cross-sectional study. SETTING: Academic hospital. PATIENT(S): Two
      hundred ninety-eight consecutive women with PCOS, of whom 120 were obese (body
      mass index [BMI] >=30 kg/m(2)) and 178 nonobese (BMI <30 kg/m(2)).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Comprehensive evaluation of
      cardiovascular risk factors, including 75-g oral glucose tolerance test, office
      blood pressure, lipid profile, and low-grade inflammatory markers. RESULT(S):
      Patients with AH (AH-PCOS) had higher insulin circulating levels and lower
      insulin sensitivity than their counterparts without AH (non-AH-PCOS). Obesity,
      but not AH, was the main contributor to the presence of glucose tolerance
      disorders. Both obesity and AH increased the prevalence of prehypertension and
      hypertension. AH diminished high-density lipoprotein (HDL) levels in nonobese
      PCOS women in parallel with a decrease in total cholesterol levels, leading to a
      total to HDL cholesterol ratio similar to that of nonobese non-AH-PCOS patients.
      Furthermore, AH blunted the deleterious effect of obesity on the total
      cholesterol/HDL ratio, with the ratio of obese AH-PCOS patients being similar to
      that of nonobese PCOS patients with or without AH. CONCLUSION(S): The presence of
      AH in women with PCOS is associated with reduced insulin sensitivity and
      increased blood pressure but may have beneficial impact on the lipid profile.
      Obesity is the main determinant of the clustering of cardiovascular risk factors
      in PCOS women.

PMID- 25585505
TI  - Testing and interpreting measures of ovarian reserve: a committee opinion.
AB  - Currently there is no uniformly accepted definition of decreased ovarian reserve
      (DOR), as the term may refer to three related but distinctly different outcomes:
      oocyte quality, oocyte quantity, or reproductive potential. Available evidence
      concerning the performance of ovarian reserve tests is limited by small sample
      sizes, heterogeneity among study design, analyses and outcomes, and the lack of
      validated outcome measures. 

PMID- 25585506
TI  - Optimizing human semen cryopreservation by reducing test vial volume and
      repetitive test vial sampling.
AB  - OBJECTIVE: To investigate optimal test vial (TV) volume, utility and reliability
      of TVs, intermediate temperature exposure (-88 degrees C to -93 degrees C) before
      cryostorage, cryostorage in nitrogen vapor (VN2) and liquid nitrogen (LN2), and
      long-term stability of VN2 cryostorage of human semen. DESIGN: Prospective
      clinical laboratory study. SETTING: University assisted reproductive technology
      (ART) laboratory. PATIENT(S): A total of 594 patients undergoing semen analysis
      and cryopreservation. INTERVENTION(S): Semen analysis, cryopreservation with
      different intermediate steps and in different volumes (50-1,000 MUL), and long
      term storage in LN2 or VN2. MAIN OUTCOME MEASURE(S): Optimal TV volume,
      prediction of cryosurvival (CS) in ART procedure vials (ARTVs) with pre-freeze
      semen parameters and TV CS, post-thaw motility after two- or three-step semen
      cryopreservation and cryostorage in VN2 and LN2. RESULT(S): Test vial volume of
      50 MUL yielded lower CS than other volumes tested. Cryosurvival of 100 MUL was
      similar to that of larger volumes tested. An intermediate temperature exposure (
      88 degrees C to -93 degrees C for 20 minutes) during cryopreservation did not
      affect post-thaw motility. Cryosurvival of TVs and ARTVs from the same ejaculate
      were similar. Cryosurvival of the first TV in a series of cryopreserved
      ejaculates was similar to and correlated with that of TVs from different
      ejaculates within the same patient. Cryosurvival of the first TV was correlated
      with subsequent ARTVs. Long-term cryostorage in VN2 did not affect CS.
      CONCLUSION(S): This study provides experimental evidence for use of a single 100
      MUL TV per patient to predict CS when freezing multiple ejaculates over a short
      period of time (<10 days). Additionally, semen cryostorage in VN2 provides a
      stable and safe environment over time.

PMID- 25585507
TI  - Lack of association between oxidative stress-related gene polymorphisms and
      chronic migraine in an Italian population.
AB  - Migraine patients present increased risks of vascular diseases such as high blood
      pressure, insulin resistance, metabolic syndrome, stroke and coronary heart
      disease. Oxidative stress (OS) is increasingly being studied in relation to the
      pathophysiology of migraine, stimulated by the described association with the
      most frequent migraine comorbidities. Because many of the gene-encoded players of
      the OS balance are characterized by functional polymorphisms, it is supposed that
      the individual genomic profile could affect susceptibility to OS and to related
      pathophysiological conditions. This study aimed to characterize a panel of 10
      polymorphisms in 8 OS-related genes in a chronic migraine (CM) population and
      healthy controls, to recognize a genetic risk in the process of migraine
      chronification. The sample consisted of 45 healthy women and 96 women diagnosed
      with CM. No deviations from the Hardy-Weinberg equilibrium were detected, or in
      the overall population, or in the CM group or in the control group. 

PMID- 25585508
TI  - Evolution of small guide RNA genes in hyperthermophilic archaea.
AB  - Profiling the RNA production in hyperthermophilic archaea revealed an abundance
      of small RNA-guided processes near the upper temperature limit of life. Archaea
      utilize the base-pairing ability of RNA guide sequences to target ribosomal RNAs,
      transfer RNAs, messenger RNAs, and viral genomes. Cellular processes that are
      guided by small RNAs include the modification of RNA molecules, trans-splicing,
      gene regulation, and RNA and DNA degradation. Here, a brief overview of our
      knowledge on small guide RNA genes in archaeal genomes is provided and examples
      of their putative roles in genome evolution are described. 

PMID- 25585509
TI  - Efficacy of Hedgehog pathway inhibitors in Basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is the most commonly diagnosed cancer. While most BCCs
      are amenable to surgery, some tumors can reach a more advanced stage or
      metastasize, and become ineligible for surgical resection or radiotherapy.
      Abnormal activation of the Hedgehog (Hh) pathway is a key driver in BCC
      pathophysiology. Consequently, inhibitors of the Hh pathway have been developed.
      Molecules that inhibit the receptor protein Smoothened (SMO) are the most
      advanced in clinical development. Vismodegib is the first-in-class SMO inhibitor
      and has been approved in a number of countries for the treatment of metastatic or
      locally advanced BCC. Several molecules have demonstrated antitumoral activity,
      but treatment may be limited in duration by a number of side effects, and it is
      not yet established whether these agents are truly curative or whether continued
      treatment will be required. Resistance to SMO inhibition has been reported in the
      clinic for which incidence and mechanisms must be elucidated to inform future
      therapeutic strategies. Intermittent dosing regimens to improve tolerability, as
      well as neoadjuvant use of Hh pathway inhibitors, are currently under
      investigation. Here, we review the most recent outcomes obtained with Hh
      inhibitors under clinical investigation in BCC.

PMID- 25585510
TI  - REM Sleep-Dependent Bidirectional Regulation of Hippocampal-Based Emotional
      Memory and LTP.
AB  - Prolonged rapid-eye-movement (REM) sleep deprivation has long been used to study
      the role of REM sleep in learning and memory processes. However, this method
      potentially induces stress and fatigue that may directly affect cognitive
      functions. Here, by using a short-term and nonstressful REM sleep deprivation
      (RSD) method we assessed in rats the bidirectional influence of reduced and
      increased REM sleep amount on hippocampal-dependent emotional memory and
      plasticity. Our results indicate that 4 h RSD impaired consolidation of
      contextual fear conditioning (CFC) and induction of long-term potentiation (LTP),
      while decreasing density of Egr1/Zif268-expressing neurons in the CA1 region of
      the dorsal hippocampus. LTP and Egr1 expression were not affected in ventral CA1.
      Conversely, an increase in REM sleep restores and further facilitates CFC
      consolidation and LTP induction, and also increases Egr1 expression in dorsal
      CA1. Moreover, CFC consolidation, Egr1 neuron density, and LTP amplitude in
      dorsal CA1 show a positive correlation with REM sleep amount. Altogether, these
      results indicate that mild changes in REM sleep amount bidirectionally affect
      memory and synaptic plasticity mechanisms occurring in the CA1 area of the dorsal
      hippocampus. 

PMID- 25585511
TI  - Exploring the association between resistance and outpatient antibiotic use
      expressed as DDDs or packages.
AB  - OBJECTIVES: The objective of this study was to explore the association between
      resistance and outpatient antibiotic use, expressed as either DDDs per 1000
      inhabitants per day (DID) or packages per 1000 inhabitants per day (PID).
      METHODS: IMS Health data on outpatient penicillin and cephalosporin (beta-lactam)
      and tetracycline, macrolide, lincosamide and streptogramin (TMLS) use, aggregated
      at the level of the active substance (WHO version 2011) expressed as DID and PID
      (2000-07) were linked to European Antimicrobial Resistance Surveillance System
      (EARSS) data on proportions of penicillin-non-susceptible Streptococcus
      pneumoniae (PNSP) and erythromycin-non-susceptible S. pneumoniae (ENSP) (2000
      09). Combined data for 27 European countries were analysed with a generalized
      linear mixed model. Model fit for use in DID, PID or both and 0, 1 or 2 year time
      lags between use and resistance was assessed and predictions of resistance were
      made for decreasing use expressed as DID, PID or both. RESULTS: When exploring
      the association between beta-lactam use and PNSP, the best model fit was obtained
      for use in PID without time lag. For the association between TMLS use and ENSP,
      the best model fit was obtained for use in both PID and DID with a 1 year time
      lag. PNSP and ENSP are predicted to decrease when use decreases in PID, but not
      when use decreases in DID. CONCLUSIONS: Associations between outpatient
      antibiotic use and resistance and predictions of resistance were inconsistent
      whether expressing antibiotic use as DID or PID. We recommend that data on
      antibiotic use be expressed as PID and that time lags between use and resistance
      be considered when exploring these associations.

PMID- 25585512
TI  - UK trainee doctors are still unsure about how to treat anaphylaxis.

PMID- 25585513
TI  - Addressing policy needs for prevention and control of type 2 diabetes in India.
AB  - India carries nearly one-fifth of the global burden of diabetes cases, the
      majority of which are of type 2 diabetes. Recognising the need for controlling
      diabetes, the Government of India has initiated a national level programme for
      prevention and control of diabetes along with other non-communicable diseases in
      2008. Despite being piloted and implemented, there is hardly any published
      literature about the national level situation of diabetes and its control
      efforts. The present article is written with the aim to fill this gap to some
      extent and to provide a situational analysis of the diabetes problem in India in
      a holistic way, addressing policy needs for the national programme. It focuses on
      three main areas, namely, awareness of diabetes, costs of drugs for its treatment
      and healthcare-system related issues. It argues that poor coverage and weak
      implementation of the national level programme are major forces that push
      patients to seek help in the weakly regulated private sector. Approaching the
      private sector is likely to increase the cost of care, which in turn can lead to
      an increased financial burden for patients and their families due to factors such
      as patients' lack of awareness about diabetes, poor drug price regulation and
      prescriptions including combinations and/or patented products of medicines used
      for treating diabetes by the private sector. This article addresses several needs
      such as strengthening the national programme and increasing its reach to
      unreached districts, exerting drug price regulation and implementing community
      based participatory programmes for prevention and management of type 2 diabetes.
      It also underscores a need for piloting and implementing a robust national level
      electronic reporting system for diabetes programmes. 

PMID- 25585515
TI  - Embodied-enactive clinical reasoning in physical therapy.
AB  - Clinical reasoning is essential in physical therapy practice. Instrumental
      approaches and more recent narrative approaches to clinical reasoning guide
      physical therapists in their understanding of the patient's movement disturbances
      and help them to plan strategies to improve function. To the extent that
      instrumental and/or narrative models of clinical reasoning represent impairments
      as mere physical disturbances, we argue that such models remain incomplete. We
      draw on a phenomenologically inspired approach to embodied cognition (termed
      "enactivism") to suggest that the dynamics of lived bodily engagement between
      physical therapist and patient contribute to and help to constitute the clinical
      reasoning process. This article outlines the phenomenologically informed enactive
      perspective on clinical reasoning, with special reference to clinical work that
      addresses impairments as sequelae of neurological diseases. 

PMID- 25585516
TI  - Patients' mental models and adherence to outpatient physical therapy home
      exercise programs.
AB  - Within physical therapy, patient adherence usually relates to attending
      appointments, following advice, and/or undertaking prescribed exercise. Similar
      to findings for general medical adherence, patient adherence to physical therapy
      home exercise programs (HEP) is estimated between 35 and 72%. Adherence to HEPs
      is a multifactorial and poorly understood phenomenon, with no consensus regarding
      a common theoretical framework that best guides empirical or clinical efforts.
      Mental models, a construct used to explain behavior and decision-making in the
      social sciences, may serve as this framework. Mental models comprise an
      individual's tacit thoughts about how the world works. They include assumptions
      about new experiences and expectations for the future based on implicit
      comparisons between current and past experiences. Mental models play an important
      role in decision-making and guiding actions. This professional theoretical
      article discusses empirical research demonstrating relationships among mental
      models, prior experience, and adherence decisions in medical and physical therapy
      contexts. Specific issues related to mental models and physical therapy patient
      adherence are discussed, including the importance of articulation of patients'
      mental models, assessment of patients' mental models that relate to exercise
      program adherence, discrepancy between patient and provider mental models, and
      revision of patients' mental models in ways that enhance adherence. The article
      concludes with practical implications for physical therapists and recommendations
      for further research to better understand the role of mental models in physical
      therapy patient adherence behavior. 

PMID- 25585517
TI  - Reliability of the chin tuck neck flexion test for assessing endurance of short
      neck flexors in healthy individuals.
AB  - OBJECTIVES: The aim of the study was to examine of the intra-rater reliability of
      the chin tuck neck flexion (CTNF) test for assessing the endurance of neck
      flexors. MATERIALS AND METHODS: The study was performed at the Cardiorespiratory
      laboratory of the Physiotherapy Department, School of Health and Caring
      Professions, TEI Lamia, Greece. Twenty healthy volunteers (males/females: 9/11,
      age: 22.2 +/- 1.7 y ears) with no known musculoskeletal, cardiovascular,
      pulmonary, neurological, or psychiatric disorder were recruited. The participants
      were positioned in a supine position and were asked to raise their head 2.5 cm
      above the plinth and to maintain this position for as long as possible without
      losing craniocervical or cervical flexion. This test was repeated three times
      with 5-min intervals between the trials. RESULTS: The results showed that this
      test could discriminate between neck flexor endurance in men and women. However,
      although the test seems to be highly reliable (ICC: 0.81-0.88), it presents
      unsatisfactory standard error of measurement (SEM: 10.7-14.7 s) and smallest
      detectable differences (SDD: 80.5-110.9%). Furthermore, subgroup analysis showed
      the test seems to be more reliable for women (ICC: 0.93-0.94) than for men (ICC:
      0.68-0.8), but the SEM and SDD values for them remain unsatisfactory (SEM: 4.4
      5.3 s, SDD: 57.5-63.99%). CONCLUSIONS: Due to high reproducibility and
      discriminant validity, clinicians and researchers might want to consider using
      the CTNF test for the assessment of neck flexor endurance. However, they should
      seek alternative measurement tools when they want to avoid a large measurement
      error.

PMID- 25585514
TI  - Muscular pre-conditioning using light-emitting diode therapy (LEDT) for high
      intensity exercise: a randomized double-blind placebo-controlled trial with a
      single elite runner.
AB  - Recently, low-level laser (light) therapy (LLLT) has been used to improve muscle
      performance. This study aimed to evaluate the effectiveness of near-infrared
      light-emitting diode therapy (LEDT) and its mechanisms of action to improve
      muscle performance in an elite athlete. The kinetics of oxygen uptake (VO2),
      blood and urine markers of muscle damage (creatine kinase--CK and alanine), and
      fatigue (lactate) were analyzed. Additionally, some metabolic parameters were
      assessed in urine using proton nuclear magnetic resonance spectroscopy ((1)H
      NMR). A LED cluster with 50 LEDs (lambda = 850 nm; 50 mW 15 s; 37.5 J) was
      applied on legs, arms and trunk muscles of a single runner athlete 5 min before a
      high-intense constant workload running exercise on treadmill. The athlete
      received either Placebo-1-LEDT; Placebo-2-LEDT; or Effective-LEDT in a randomized
      double-blind placebo-controlled trial with washout period of 7 d between each
      test. LEDT improved the speed of the muscular VO2 adaptation (~-9 s), decreased
      O2 deficit (~-10 L), increased the VO2 from the slow component phase (~+348 ml
      min(-1)), and increased the time limit of exercise (~+589 s). LEDT decreased
      blood and urine markers of muscle damage and fatigue (CK, alanine and lactate
      levels). The results suggest that a muscular pre-conditioning regimen using LEDT
      before intense exercises could modulate metabolic and renal function to achieve
      better performance.

PMID- 25585518
TI  - Expanding the toolbox of asymmetric organocatalysis by continuous-flow process.
AB  - Despite all the organic chemistry reaction methodologies already developed for
      the continuous-flow process, asymmetric synthesis is one that has gained less
      attention. Since the pioneering work of Barbas and MacMillan, organocatalysis has
      emerged as the third pillar of asymmetric catalysis. In this review, we present a
      survey of literature regarding the use of organocatalysis under continuous-flow
      conditions. 

PMID- 25585519
TI  - Changes of quality in the fruits of Prunus mume during deacidification by
      fermentation with Lactobacillus fermentium.
AB  - The aim of this study was to investigate the changes of quality attributes of
      Prunus mume fruits during deacidification using the fermentation of Lactobacillus
      fermentium. Results of HPLC analysis showed that the sucrose and glucose were
      dominant sugars, and citric acid was dominant organic acids in P. mume fruits.
      The level of citric acid reaches 39.3 g/kg, and yet the sucrose and glucose
      content in the P. mume fruits was very lower, which were 2.16 and 0.66 g/L,
      respectively. After 8 d of fermentation, sugar and citric acid in the P. mume
      fruits was completely consumed, and the total phenolics, antioxidant activity
      (oxygen radical absorbance capacity value), and sarcocarp firmness retained
      64.4%, 70.0%, 62.6%, respectively. Also, the viability counts of L. fermentium in
      fermentation broth increased slowly, which were near 8.0 lg CFU/mL after 8 d of
      fermentation at 30  degrees C. Overall, fermentation with L. fermentium can be
      applied in deacidification of P. mume fruits, and also the fermented P. mume
      fruits can meet the standard to be further processed into prune or sauces, and
      the fermentation broth of P. mume fruits with L. fermentium have a good prospect
      in the development of probiotic beverage. 

PMID- 25585521
TI  - Range verification of passively scattered proton beams using prompt gamma-ray
      detection.
AB  - We performed an experimental study to verify the range of passively scattered
      proton beams by detecting prompt gamma-rays emitted from proton-nuclear
      interactions. A method is proposed using a single scintillation detector
      positioned near the distal end of the irradiated target. Lead shielding was used
      to attenuate gamma-rays emitted along most of the entrance path of the beam. By
      synchronizing the prompt gamma-ray detector to the rotation of the range
      modulation wheel, the relation between the gamma emission from the distal part of
      the target and the range of the incident proton beam was determined. In
      experiments with a water phantom and an anthropomorphic head phantom, this
      relation was found to be sensitive to range shifts that were introduced. The wide
      opening angle of the detector enabled a sufficient signal-to-background ratio to
      be achieved in the presence of neutron-induced background from the scattering and
      collimating devices. Uniform range shifts were detected with a standard deviation
      of 0.1 mm to 0.2 mm at a dose level of 30 cGy to 50 cGy (RBE). The detectable
      magnitude of a range shift limited to a part of the treatment field area was
      approximately proportional to the ratio between the field area and the area
      affected by the range shift. We conclude that it is feasible to detect changes in
      the range of passively scattered proton beams using a relatively simple prompt
      gamma-ray detection system. The method can be employed for in vivo verification
      of the consistency of the delivered range in fractionated treatments.

PMID- 25585520
TI  - Inhibition of transforming growth factor-beta via the activin receptor-like
      kinase-5 inhibitor attenuates pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis is a chronic pulmonary disease that is
      characterized by formation of scar tissue in lungs. Transforming growth factor
      beta (TGF-beta) is considered an important cytokine in the pathogenesis of this
      disease. Hence, the antifibrotic effect of an inhibitor of the TGF-beta type I
      receptor, namely, SB 431542, was investigated in our study. SB 431542 was used to
      treat TGF-beta-treated IMR-90 cells; the expression of alpha-smooth muscle actin
      (alpha-SMA) was detected at the protein level by using an anti-alpha-SMA
      antibody, and at the gene level by reverse transcription-quantitative PCR. The
      effect of the inhibitor on cell proliferation was determined by a cell growth
      assay. The inhibitor was also administered into bleomycin-treated mice.
      Histopathological assessment and determination of total collagen levels were
      carried out to evaluate the severity of lung fibrosis in these mice. Our results
      demonstrated that treatment with SB 431542 inhibits TGF-beta-induced alpha-SMA
      expression in lung fibroblasts, at both the protein and the mRNA levels (P<0.05).
      However, the inhibitor did not significantly reduce lung fibroblast
      proliferation. In the bleomycin-induced pulmonary fibrosis mouse model, bleomycin
      treatment caused important morphological changes, accompanied by an increase in
      the collagen level of the lungs. Early treatment with SB 431542 prevented the
      manifestation of histopathological alterations, whereas delayed treatment
      significantly decreased the collagen level (P<0.05). These results suggest that
      inhibition of TGF-beta signaling, via inhibition of the activin receptor-like
      kinase-5 (ALK-5) by SB 431542, may attenuate pulmonary fibrosis.

PMID- 25585522
TI  - Surgical treatment of systemic sclerosis--is it justified to offer peripheral
      sympathectomy earlier in the disease process?
AB  - PURPOSE: Systemic sclerosis (SSc) is a rare connective tissue disease associated
      with significant digital vasculopathy. Peripheral sympathectomy is frequently
      offered late in the disease process after severe digital ischemia has already
      occurred with patients being symptomatic for numerous years. The purpose of the
      present study was to analyze the results of peripheral sympathectomy in patients
      with a confirmed diagnosis of SSc. PATIENTS AND METHODS: A retrospective analysis
      of 17 patients (26 hands) who underwent peripheral sympathectomy between January
      2003 and September 2013 was performed. Data regarding patient demographics,
      clinical features, and postoperative outcomes were retrieved. Of note,
      preoperative pain was present in all patients with a mean duration of 9.6 years
      prior to peripheral sympathectomy. RESULTS: Pain improvement/resolution was seen
      in 24 hands (92.3%). Digital ulcers healed in all patients with only two patients
      (two hands; 7.7%) requiring surgical intervention for ulcer recurrence 6 months
      and 4.5 years later. Minor complications were seen in seven hands (26.9%);
      including infection, wound opening, and stitch abscess, but none required
      surgical intervention. Seven of eight patients queried would have preferred
      surgical treatment at an earlier point in the disease process. CONCLUSION:
      Peripheral sympathectomy is a well-tolerated procedure in patients with SSc and
      is associated with predictable pain relief and ulcer healing in the majority of
      patients. In light of these findings it seems prudent to offer surgical treatment
      not as a last resort but rather earlier in the disease process to decrease the
      duration that patients suffer pain.

PMID- 25585523
TI  - Phenotypic and molecular characterization of 942 carbapenem-resistant
      Enterobacteriaceae (CRE) in southern Brazil.
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) is a major international health
      problem, and its identification in developing countries is based exclusively on
      phenotypic methods. The aim of this study was to assess the sensitivity and
      related parameters of the modified Hodge test (MHT). The assessment was performed
      in a large number of isolates obtained from different hospitals in several cities
      of a south Brazilian state. Bacterial species were identified using an automated
      method. The MHT was performed according to the guidelines set by the CLSI. The
      gene blaKPC was amplified in order to confirmation CRE expression. The
      sensitivity, specificity, positive, and negative predictive values were
      calculated. A total of 942 isolates were submitted to the reference laboratory
      for confirmation; 143 showed a negative MHT (15.18%) result, while 784 were
      positive (83.23%), and 15 samples displayed an indeterminate MHT (1.59%) result.
      All samples expressed the KPC-2 enzyme. Sensitivity, specificity, positive, and
      negative predictive percentiles were 99%, 89%, 98%, and 99% respectively. We
      conclude that the modified Hodge test is a reliable test for the prediction of
      KPC-producing bacteria. 

PMID- 25585524
TI  - B-type natriuretic peptide-guided risk assessment for postoperative complications
      in lung cancer surgery.
AB  - BACKGROUND: Since lung cancer surgery is still associated with a high
      complication rate, it is important to efficiently identify patients at high risk
      for postoperative complications following lung cancer surgery. We previously
      reported that elderly patients with elevated preoperative B-type natriuretic
      peptide (BNP) levels (>30 pg/mL) have an increased risk for postoperative atrial
      fibrillation and cardiopulmonary complications following lung cancer surgery. The
      objective of this study was to evaluate the clinical utility of BNP-guided risk
      classification for postoperative complications after lung cancer surgery.
      METHODS: A total of 675 consecutive patients who underwent curative surgery for
      lung cancer in two specialized thoracic centers between 2007 and 2011 were
      included in this retrospective study. We evaluated the association between the
      incidence of postoperative complications and preoperative BNP levels. RESULTS:
      Univariable and multivariable stepwise logistic regression analyses revealed that
      an elevated preoperative BNP level was the most significant predictor of
      postoperative complications. All patients were classified by their preoperative
      BNP levels into a normal group (<30 pg/mL), a mildly elevated group (30-100
      pg/mL), and a severely elevated group (>100 pg/mL). The incidence of
      postoperative complications was significantly higher in the severely and mildly
      elevated groups than in the control group (85 % and 47 % vs. 11 %, P < 0.0001).
      Furthermore, there were more severe complications and a higher mortality rate in
      the severely elevated group. CONCLUSIONS: Risk assessment using preoperative BNP
      levels was clinically useful for the identification of patients at high risk for
      postoperative complications.

PMID- 25585525
TI  - Safety and feasibility of laparoscopic hepatectomy for hepatocellular carcinoma
      in the posterosuperior liver segments.
AB  - BACKGROUND: Laparoscopic hepatectomy (LH) is mostly performed to treat solitary
      tumors in the anterolateral liver segments (II, III, IVb, V, and VI). Few reports
      are available on LH for the treatment of hepatocellular carcinoma (HCC) in the
      posterosuperior liver segments (I, IVa, VII, and VIII), especially in association
      with cirrhosis. The purpose of this study was to investigate the safety and
      feasibility of LH in this clinical setting. METHODS: From January 2008 to January
      2011, LH was conducted in 56 patients with HCC in the posterosuperior liver
      segments (PS group) and 70 patients with HCC in the anterolateral liver segments
      (AL group) who were admitted to Southwest Hospital of the Third Military Medical
      University, Chongqing, China. The clinical data and follow-up results in the two
      groups of patients were retrospectively analyzed. RESULTS: No patient in either
      group died during the perioperative period. Statistically significant differences
      were found between the PS and AL groups in terms of the operation time (217.5 +/-
      63.7 vs 176.8 +/- 48.4 min, P = 0.000), volume of blood loss (295.5 +/- 186.8 vs
      220.4 +/- 164.2 ml, P = 0.001), conversion rate from laparoscopy to laparotomy
      (17.9 vs 7.1 %, P = 0.031), transfusion rate (16.1 vs 4.3 %, P = 0.025), cases of
      hepatic inflow occlusion (38/18 vs 28/42, P = 0.002), and duration of inflow
      occlusion (41.3 +/- 16.3 vs 31.3 +/- 12.2 min, P = 0.005). Parameters with no
      significant differences between the two groups of patients included tumor size
      (4.0 +/- 1.5 vs 3.9 +/- 1.7 cm, P = 0.894), resection margin (1.7 +/- 0.7 vs 1.8
      +/- 0.6 cm, P = 0.102), postoperative complication rate (16.1 vs 17.1 %, P =
      0.873), postoperative anal exhaust time (3.2 +/- 0.6 vs 3.0 +/- 0.6 days, P =
      0.361), and postoperative hospital stay (10.5 +/- 2.7 vs 10.0 +/- 0.6 days, P =
      0.102). The serum alanine transaminase (ALT) and aspartate aminotransferase (AST)
      levels on postoperative days 1 and 3 were significantly higher in the PS group
      than in the AL group. There were no significant differences in the postoperative
      levels of the serum total bilirubin, albumin, ALT, or AST levels on postoperative
      days 5 and 7. After 2-48 months of follow-up, no significant differences in the 1
      and 3-year overall survival rates (92.9 vs 95.7 %, P = 0.487 and 76.0 vs 76.8 %,
      P = 0.878, respectively) or 1- and 3-year disease-free survival rates (85.7 vs
      87.1 %, P = 0.797 and 57.6 vs 56.4 %, P = 0.806, respectively) were noted between
      the two groups. CONCLUSIONS: LH is safe and feasible for selected patients with
      HCC in the posterosuperior segments of the liver.

PMID- 25585527
TI  - Virtually compliant: Immersive video gaming increases conformity to false
      computer judgments.
AB  - Real-life encounters with face-to-face contact are on the decline in a world in
      which many routine tasks are delegated to virtual characters-a development that
      bears both opportunities and risks. Interacting with such virtual-reality beings
      is particularly common during role-playing videogames, in which we incarnate into
      the virtual reality of an avatar. Video gaming is known to lead to the training
      and development of real-life skills and behaviors; hence, in the present study we
      sought to explore whether role-playing video gaming primes individuals'
      identification with a computer enough to increase computer-related social
      conformity. Following immersive video gaming, individuals were indeed more likely
      to give up their own best judgment and to follow the vote of computers,
      especially when the stimulus context was ambiguous. Implications for human
      computer interactions and for our understanding of the formation of identity and
      self-concept are discussed. 

PMID- 25585526
TI  - Management of retropharyngeal node metastases from thyroid carcinoma.
AB  - BACKGROUND: Lymph node metastases are relatively common in thyroid carcinoma, but
      retropharyngeal nodes (RPN) are rare. Management may be surgical or non-surgical,
      according to the context of the disease. METHODS: Systematic review of cases
      reported in the literature and report of 5 cases. RESULTS: Most case series
      report surgical management, via a cervical or transoral approach. RPN was the
      specific object of 26 case series, with a total of 85 patients, with surgery
      performed in 22/26 studies. Our 5 cases illustrated various strategies in the
      multidisciplinary management, with surgery for three patients (also with (131)I
      in one case), targeted therapy for one patient with concurrent distant
      metastases, and watch and wait for one elderly patient. CONCLUSIONS: Management
      of RPN is not always surgical. Discussion of options in a multidisciplinary tumor
      board setting may optimize care.

PMID- 25585529
TI  - A 36-fold multiple unit cell and switchable anisotropic dielectric responses in
      an ammonium magnesium formate framework.
AB  - An ammonium Mg formate framework, prepared by using di-protonated 1,3
      propanediamine (pnH2(2+)), has a rare three-dimensional binodal
      (4(12)?6(3))(4(9)?6(6))3 Mg-formate framework with elongated cavities
      accommodating pnH2(2+)???H2O???pnH2(2+) assemblies. It displays a para-electric
      to antiferroelectric phase transition at 275 K, with a 36-fold multiple unit cell
      from the high-temperature cell of 1703 A(3) to the low-temperature one of 60,980
      A(3). The change results from the disorder-order transition of the pnH2(2+)
      cations and H2O molecules. The motions of these components freeze in a stepwise
      fashion on going from the high-temperature disorder state to the low-temperature
      ordered state, triggering the switch from high to low dielectric constants, and
      the spatial limitation of such motions contributes the strong dielectric
      anisotropy.

PMID- 25585528
TI  - The Intelence aNd pRezista Once A Day Study (INROADS): a multicentre, single-arm,
      open-label study of etravirine and darunavir/ritonavir as dual therapy in HIV-1
      infected early treatment-experienced subjects.
AB  - OBJECTIVES: Following antiretroviral therapy failure, patients are often treated
      with a three-drug regimen that includes two nucleoside/tide reverse transcriptase
      inhibitors [N(t)RTIs]. An alternative two-drug nucleoside-sparing regimen may
      decrease the pill burden and drug toxicities associated with the use of N(t)RTIs.
      The Intelence aNd pRezista Once A Day Study (INROADS; NCT01199939) evaluated the
      nucleoside-sparing regimen of etravirine 400 mg with darunavir/ritonavir 800/100
      mg once-daily in HIV-1-infected treatment-experienced subjects or treatment-naive
      subjects with transmitted resistance. METHODS: In this exploratory phase 2b,
      single-arm, open-label, multicentre, 48-week study, the primary endpoint was the
      proportion of subjects who achieved HIV-1 RNA < 50 copies/mL at week 48
      [confirmed virological response (CVR), non-virological failure (VF) censored].
      Key secondary endpoints included assessments of changes from baseline to week 48
      in viral load, immunological response, pharmacokinetics/pharmacodynamics, safety,
      tolerability, metabolic and bone markers and body fat. RESULTS: Forty-one of the
      54 enrolled subjects completed the study. Adverse events (7%) and VF (7%) were
      the most common reasons for discontinuation. The week 48 CVR rate in the intent
      to-treat (ITT) non-VF censored population was 89% (primary endpoint). Seven
      subjects experienced VF. Common adverse events were diarrhoea (15%), rash (15%)
      and upper respiratory tract infection (11%). Mild/moderate lipid elevations,
      minimal changes in limb fat distribution and bone mineral density and no
      clinically relevant changes in glucose metabolism were observed. CONCLUSIONS:
      Etravirine 400 mg and darunavir/ritonavir 800/100 mg as a two-drug once-daily
      regimen in treatment-experienced subjects or treatment-naive subjects with
      transmitted resistance was virologically efficacious and well tolerated.

PMID- 25585530
TI  - Genetic analysis of amyotrophic lateral sclerosis in the Slovenian population.
AB  - Amyotrophic lateral sclerosis (ALS) is a complex fatal neurodegenerative disease
      characterized by progressive degeneration and loss of upper motor neurons in the
      cerebral cortex and lower motor neurons in brainstem and spinal cord. We
      established the frequencies of mutations in 4 major ALS-associated genes, SOD1,
      TARDBP, FUS, and C9ORF72 in a representative cohort of 85 Slovenian patients with
      sporadic form of ALS. Pathogenic massive hexanucleotide repeat expansion mutation
      in C9ORF72 was detected in 5.9% of patients and was the most common cause of the
      disease. In the remaining 3 genes, we identified 4 changes in 3 patients,
      p.Val14Met in SOD1, silent mutation p.Arg522Arg in FUS, and p.Gly93Cys in SOD1
      together with a novel synonymous variant c.990A>G (p.Leu330Leu) in TARDBP gene,
      respectively. This study represents the first genetic screening of major
      causative genes for ALS in a cohort of sporadic ALS patients from Slovenia and is
      according to our knowledge the first such study in Slavic population. Overall, we
      genetically characterized 8.2% sporadic ALS patients. 

PMID- 25585531
TI  - Blood methylomic signatures of presymptomatic dementia in elderly subjects with
      type 2 diabetes mellitus.
AB  - Due to an aging population, the incidence of dementia is steadily rising. The
      ability to identify early markers in blood, which appear before the onset of
      clinical symptoms is of considerable interest to allow early intervention,
      particularly in "high risk" groups such as those with type 2 diabetes. Here, we
      present a longitudinal study of genome-wide DNA methylation in whole blood from
      18 elderly individuals with type 2 diabetes who developed presymptomatic dementia
      within an 18-month period following baseline assessment and 18 age-, sex-, and
      education-matched controls who maintained normal cognitive function. We
      identified a significant overlap in methylomic differences between groups at
      baseline and follow-up, with 8 CpG sites being consistently differentially
      methylated above our nominal significance threshold before symptoms at baseline
      and at 18 months follow up, after a diagnosis of presymptomatic dementia.
      Finally, we report a significant overlap between DNA methylation differences
      identified in converters, only after they develop symptoms of dementia, with
      differences at the same loci in blood samples from patients with clinically
      diagnosed Alzheimer's disease compared with unaffected control subjects.

PMID- 25585532
TI  - Trajectories of memory decline in preclinical Alzheimer's disease: results from
      the Australian Imaging, Biomarkers and Lifestyle Flagship Study of ageing.
AB  - Memory changes in preclinical Alzheimer's disease (AD) are often characterized by
      heterogenous trajectories. However, data regarding the nature and determinants of
      predominant trajectories of memory changes in preclinical AD are lacking. We
      analyzed data from 333 cognitively healthy older adults who participated in a
      multicenter prospective cohort study with baseline and 18-, 36-, and 54-month
      follow-up assessments. Latent growth mixture modeling revealed 3 predominant
      trajectories of memory change: a below average, subtly declining memory
      trajectory (30.9%); a below average, rapidly declining memory trajectory (3.6%);
      and an above average, stable memory trajectory (65.5%). Compared with the stable
      memory trajectory, high Alphabeta (relative risk ratio [RRR] = 2.1), and lower
      Mini-Mental State Examination (RRR = 0.6) and full-scale IQ (RRR = 0.9) scores
      were independently associated with the subtly declining memory trajectory; and
      high Alphabeta (RRR = 8.3), APOE epsilon4 carriage (RRR = 6.1), and greater
      subjective memory impairment (RRR = 1.2) were independently associated with the
      rapidly declining memory trajectory. Compared with the subtly declining memory
      trajectory group, APOE epsilon4 carriage (RRR = 8.4), and subjective memory
      complaints (RRR = 1.2) were associated with a rapidly declining memory
      trajectory. These results suggest that the preclinical phase of AD may be
      characterized by 2 predominant trajectories of memory decline that have common
      (e.g., high Alphabeta) and unique (e.g., APOE epsilon4 genotype) determinants.

PMID- 25585533
TI  - MetaPopGen: an r package to simulate population genetics in large size
      metapopulations.
AB  - Population genetics simulation models are useful tools to study the effects of
      demography and environmental factors on genetic variation and genetic
      differentiation. They allow for studying species and populations with complex
      life histories, spatial distribution and many other complicating factors that
      make analytical treatment impracticable. Most simulation models are individual
      based: this poses a limitation to simulation of very large populations because of
      the limits in computer memory and long computation times. To overcome these
      limitations, we propose an intermediate approach that allows modelling of very
      complex demographic scenarios, which would be intractable with analytical models,
      and removes the limitations imposed by large population size, which affect
      individual-based simulation models. We implement this approach in a software
      package for the r environment, MetaPopGen. The innovative concept of this
      approach with respect to the other population genetic simulators is that it
      focuses on genotype numbers rather than on individuals. Genotype numbers are
      iterated through time by using random number generators for appropriate
      probabilistic distributions to reproduce the stochasticity inherent to Mendelian
      segregation, survival, dispersal and reproduction. Features included in the model
      are age structure, monoecious and dioecious (or separate sexes) life cycles,
      mutation, dispersal and selection. The model simulates only one locus at a time.
      All demographic parameters can be genotype-, sex-, age-, deme- and time
      dependent. MetaPopGen is therefore indicated to study large populations and very
      complex demographic scenarios. We illustrate the capabilities of MetaPopGen by
      applying it to the case of a marine fish metapopulation in the Mediterranean Sea.

PMID- 25585534
TI  - To the editor.

PMID- 25585535
TI  - Interference with the reconsolidation of trauma-related memories in adults.
AB  - BACKGROUND: Reactivated memories go through a process of reconsolidation, during
      which they are malleable and susceptible to modification. Strategies targeting
      the interruption of memory reconsolidation hold the promise of weakening fear
      memories that underlie traumatic stress disorders. Although many studies have
      examined the efficacy of reconsolidation interference strategies with fear
      memories developed in a laboratory, very few have examined this with trauma
      related episodic memories. This study aims to examine whether new learning can
      interfere with the reconsolidation of trauma-related episodic memories, when the
      affective content of the new learning and memory match. METHODS: Boston-area
      young adults (n = 94) wrote about negative autobiographical memories;
      specifically, their personal memories of the Boston Marathon bombings. Following
      reactivation, participants were randomized to receive interference with a
      negative, positive, neutral, or no story. One week later, participants were
      tested for memory recall. RESULTS: Comparisons between conditions with relevant
      covariates revealed a significant interfering effect for a negative story,
      relative to no story, on recall (P < .05, 95% CI [-3.90, -0.04]), d = 0.62). In
      contrast, the neutral and positive story, relative to no story, resulted in
      smaller and nonsignificant effects. CONCLUSIONS: These findings indicate that
      reconsolidation interference effects can be achieved for trauma-related episodic
      memories and the emotional valence of interference material may be an important
      contextual factor in achieving these effects. This study provides support for
      further research translating memory reconsolidation findings into treatments for
      traumatic stress disorders.

PMID- 25585537
TI  - Usefulness of automated feeder-detection software for identification of access
      routes to small pancreaticoduodenal artery aneurysms during embolotherapy.
AB  - The mortality rate of patients with ruptured pancreaticoduodenal artery aneurysms
      is high; therefore, it is recommended to treat pancreaticoduodenal artery
      aneurysms regardless of their size. In small pancreaticoduodenal artery
      aneurysms, however, identification of the access route on two-dimensional
      arteriography is sometimes difficult because of the superimposition of many
      hypertrophied branches of pancreaticoduodenal arteries on the aneurysm. We report
      two cases of ruptured pancreaticoduodenal artery aneurysm embolized successfully
      with metallic coils, assisted by automated feeder-detection software using cone
      beam computed tomography data. This new technology may reduce physicians'
      workload during the procedure. 

PMID- 25585538
TI  - Well-defined single-site monohydride silica-supported zirconium from
      azazirconacyclopropane.
AB  - The silica-supported azazirconacyclopropane =SiOZr(HNMe2)(eta(2)-NMeCH2)(NMe2)
      (1) leads exclusively under hydrogenolysis conditions (H2, 150  degrees C) to the
      single-site monopodal monohydride silica-supported zirconium species
      =SiOZr(HNMe2)(NMe2)2H (2). Reactivity studies by contacting compound 2 with
      ethylene, hydrogen/ethylene, propene, or hydrogen/propene, at a temperature of
      200  degrees C revealed alkene hydrogenation.

PMID- 25585541
TI  - Atomistic simulations of ammonium-based protic ionic liquids: steric effects on
      structure, low frequency vibrational modes and electrical conductivity.
AB  - Protic ionic liquids (PILs) are of great interest as electrolytes in various
      energy applications. Molecular dynamics simulations of trialkylammonium (with
      varying alkyl group such as methyl, ethyl, and n-propyl) triflate PILs are
      performed to characterize the influence of the alkyl group on the acidic site (N
      H) of the ammonium cation. Spatial distribution function of anions over this site
      on the cation reveals significant influence of the length of alkyl tail on
      intermolecular structure. Vibrational density of states and normal modes are
      calculated for bulk liquids to probe atomic displacements in the far infrared
      region. The observed N-H...O hydrogen bond stretching vibration in 155-165 cm(-1)
      frequency region agrees well with experiments. Trends in electrical conductivity
      calculated using Nernst-Einstein and Green-Kubo relation are in qualitative
      agreement with experiments. The self-diffusion coefficient and the electrical
      conductivity is highest for N,N-dimethyl-N-ethylammonium triflate ([N112][TfO])
      and is lowest for N,N-di-n-propyl-N-methylammonium triflate ([N133][TfO]) IL.

PMID- 25585540
TI  - Alternaria toxins in wheat from the Autonomous Province of Vojvodina, Serbia: a
      preliminary survey.
AB  - Although Fusarium species remain a main source of mycotoxin contamination of
      wheat, in recent years, due to the evident climatic changes, other mycotoxigenic
      fungi have been recognised as important wheat contaminants. Alternaria species,
      especially A. alternata, have been found as contaminants of wheat as well as
      wheat-based products. Under favourable conditions A. alternata very often produce
      alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA) and
      others Alternaria toxins. The aim of the present study was to examine the
      presence of three Alternaria toxins (AOH, AME and TeA) in wheat samples harvested
      during three years (2011-13). To this end, 92 samples were collected during wheat
      harvesting from different growing regions of the Autonomous Province of
      Vojvodina, which represents the most important wheat-growing area in Serbia. The
      presence of Alternaria toxins was analysed by HPLC with electrospray ionisation
      triple quadrupole mass spectrometry (LC-ESI-MS/MS). Among all the analysed wheat
      samples, 63 (68.5%) were contaminated with TeA, 11 (12.0%) with AOH and 6 (6.5%)
      with AME. Furthermore, the maximum and mean toxin concentrations were 2676 and
      92.4 ug kg(-1), 48.9 and 18.6 ug kg(-1), and 70.2 and 39.0 ug kg(-1) for TeA, AOH
      and AME, respectively. Co-occurrence of three Alternaria toxins in wheat samples
      was detected in six samples; a combination of two toxins was found in two
      samples; and 64 samples contained one toxin. The results showed that among 92
      analysed wheat samples, only 20 (21.7%) samples were without Alternaria toxins.
      The presence of Alternaria toxins was also investigated in terms of weather
      conditions recorded during the period of investigation, as well as with the
      sampling region. This study represents the first preliminary report of the
      natural occurrence of Alternaria toxins in wheat (Triticum aestivum) from Serbia.

PMID- 25585539
TI  - MiR-34a inhibits migration and invasion by regulating the SIRT1/p53 pathway in
      human SW480 cells.
AB  - MicroRNA-34a (miR-34a) is a direct transcriptional target of p53, and is
      downregulated in several different types of cancer. However, the underlying
      mechanism of the miR-34a effects in colorectal cancer is not well understood. In
      this study, we explored the role of miR-34a in cell invasion, migration, and
      apoptosis. Transient overexpression of miR-34a in SW480 cells caused a severe
      decrease in cell migration and invasion (both, p<0.05) compared to the control
      groups. Combining miR-34a transfection with 5-fluorouracil (5-FU) treatment
      further enhanced the inhibition in SW480 cell migration and invasion (both,
      p<0.05) compared to 5-FU treatment alone. These cellular changes were associated
      with upregulation of acetylated-p53 (ac-p53) and p21 and downregulation of
      sirtuin 1 (SIRT1). These data demonstrate that miR-34a regulates the expression
      of a number of critical proteins involved in apoptosis, proliferation and the
      response to chemotherapy. In summary, miR-34a increases the sensitivity of colon
      cancer cells to 5-FU treatment through specific regulation of the SIRT1/p53
      pathway.

PMID- 25585542
TI  - Comparison of complications in one-stage bilateral total knee arthroplasty with
      and without drainage.
AB  - PURPOSE: The aim of this meta-analysis was to compare the complication rates of
      one-stage bilateral total knee arthroplasty (TKA) with and without drainage in
      order to identify whether there was no clinical significance and the value of
      drainage. METHODS: Randomized controlled trials (RCTs) based on bilateral TKA
      with and without drainage were identified via a search of PubMed, EMBASE,
      Cochrane Central Register of Controlled Trials, Wanfang databases, and Google
      Scholar, which were published up to May 2014. Methodological quality was assessed
      by the Physiotherapy Evidence Database scale. After data extraction, we compared
      the outcomes using fixed-effects or random-effects models depending on the
      heterogeneity. RESULTS: Three RCTs involving 125 one-stage bilateral TKA patients
      with an average follow-up of 14 months met the predetermined inclusion criteria.
      There were 56 total complications in TKA without drainage and 17 with drainage.
      Except for less erythema and ecchymosis around the wound in the drainage group,
      there were no statistical differences in wound healing, wound infection,
      swelling, and deep vein thrombosis in one-stage bilateral TKA with and without
      drainage. CONCLUSION: The current evidences confirm that both drainage and non
      drainage have similar clinical value in one-stage bilateral TKA. However, the
      conclusion should be used with caution due to the limitations of the current
      study.

PMID- 25585543
TI  - The utility of the surgical safety checklist for wound patients.
AB  - The purpose of this study was to determine the frequency of changes in patient
      care resulting from the use of a surgical safety checklist. Data were
      retrospectively obtained from 233 patients. The number and types of changes made
      to the patients' intra-operative management, based on the use of the checklist,
      were recorded. The number of patients whose management was modified as a result
      of the checklist was 113 (48%) out of 233. The total number of changes made was
      132, and 18 patients had more than one modification made to their care plan.
      Further stratification was identified: among the 132 changes made, antibiotics
      were held or administered in 73 (55%), changes related to anaemia involving type
      and screen or transfusion occurred in 27 (20%), modifications made regarding anti
      coagulation occurred in 8 (7%), beta-blockers were held in 2 (2%), an allergy was
      identified in 7 (5%), modifications made to the surgical procedure were 3 (2%)
      and a category labelled 'other' encompassed 9 (7%) changes. The surgical safety
      checklist is a standardised form of team communication that leads to
      modifications of the patient care plan in a large percentage of cases. The ever
      increasing complexity of medicine means that patients are at greater risk of
      oversight and harm without the use of a checklist. 

PMID- 25585545
TI  - Herpes zoster vaccine: a shot to maintain wellbeing.

PMID- 25585544
TI  - Plate osteosynthesis versus hemiarthroplasty in proximal humerus fractures--does
      routine screening of systemic inflammatory biomarkers makes sense?
AB  - BACKGROUND: Increases in C-reactive protein (CRP) and white blood cell (WBC)
      counts after orthopedic surgical procedures can give evidence of postoperative
      infection. However, there is a lack of knowledge about the kinetics of these
      biomarkers in cases with an uneventful clinical course after osteosynthesis of
      upper limb fractures. This study investigated CRP and WBC serum levels after
      osteosynthesis or hemiarthroplasty of humeral head fractures. METHODS: A
      retrospective study on patients with humeral head fractures who had open
      reduction and internal fixation via plate osteosynthesis (PO) (n = 64) or
      hemiarthroplasty (HA) (n = 28) without any complications in the postoperative
      clinical course. C-reactive protein serum levels (mg/l) and leukocyte counts
      (g/l) were assayed at several time points. Multiple regression analysis was
      performed to evaluate the influence of several confounding variables (the
      surgical procedure, duration of surgery, patient's health status, and
      comorbidities) on the kinetics of CRP and WBC. RESULTS: Our data showed that CRP
      levels were statistically significantly higher in the HA cohort when compared to
      the PO cohort (p = 0.003). Moreover, daily measurement of CRP levels during the
      postoperative course showed that CRP peaked on the 2nd and 3rd days
      postoperatively in both cohorts and started to decrease afterward, reaching
      normal values on day 8 to 10. However, WBCs did not show any significant
      differences between the HA and PO cohorts. Finally, the choice of surgical
      procedure and the patient's health status were associated with higher peak levels
      of CRP. CONCLUSIONS: After osteosynthesis or hemiarthroplasty of humeral head
      fractures, CRP is a responsive serum parameter in the postoperative course of an
      uneventful inflammatory response. Abnormalities from these values should be
      interpreted carefully as they may give a hint as to postoperative complications
      such as infection.

PMID- 25585546
TI  - Concomitant hip and distal radius fractures.
AB  - BACKGROUND: Concomitant ipsilateral hip and distal radius fractures are uncommon,
      and little research has been published about these injuries. Our aim was to
      evaluate the characteristics and results of treatment for these injuries.
      METHODS: Between 2006 and 2012, 35 concomitant hip and distal radius fractures
      were identified, comprising the study group. The characteristics and results of
      treatment for these injuries were evaluated and analyzed. Another matched control
      group with isolated hip fractures was collected for comparison of patient
      characteristics, fall mechanism, fracture pattern, bone density, and functional
      recovery. RESULTS: For the patients with concomitant fractures, the average age
      was 77.6 years, and the female-to-male ratio was 6:1 (30:5). The majority (91.4%)
      of patients sustained ipsilateral injuries. Among the controlled pairs, 20
      (57.1%) patients in the study group sustained a backward fall, and 25 (71.4%)
      patients in the control group had a sideways fall. With respect to the pattern of
      hip fracture, 22 (62.9%) patients in the study group had femoral neck fractures
      and 20 (57.1%) patients in the control group had pertrochanteric fractures. The
      average hospital stay was 15.3 days in the study group versus 10.2 days in the
      control group. Twenty-five (71.4%) patients in the study group and 27 (77.1%)
      patients in the control group had osteoporosis. The average Barthel index score
      was 75.1 in the study group and 75.7 in the control group. CONCLUSION:
      Concomitant hip and distal radius fractures were generally ipsilateral and
      involved the femoral neck after a backward fall. These patients were younger than
      and not more osteoporotic than the population with isolated hip fractures;
      however, the hospital stay was significantly increased. The functional outcome
      was not influenced by concomitant wrist fracture.

PMID- 25585547
TI  - Ovarian and uterine development and hormonal feedback mechanism in a 46 XX
      patient with CYP19A1 deficiency under low dose estrogen replacement.
AB  - BACKGROUND: Aromatase deficiency may result in a complete block of estrogen
      synthesis because of the failure to convert androgens to estrogens. In females,
      this results in virilisation at birth, ovarian cysts in prepuberty and lack of
      pubertal development but virilisation, thereafter. OBJECTIVE AND METHODS: We
      studied the impact of oral 17beta-estradiol treatment on ovarian and uterine
      development, and on LH/FSH and inhibin B during the long-term follow-up of a girl
      harboring compound heterozygote point mutations in the CYP19A1 gene. RESULTS: In
      early childhood, low doses of oral 17beta-estradiol were needed. During
      prepuberty treatment with slowly increasing doses of E2 resulted in normal
      uterine and almost normal development of ovarian volume, as well as number and
      size of follicles. Regarding hormonal feedback mechanisms, inhibin B levels were
      in the upper normal range during childhood and puberty. Low doses of estradiol
      did not suffice to achieve physiological gonadotropin levels in late prepuberty
      and puberty. However, when estradiol doses were further increased in late puberty
      levels of both FSH and LH declined with estradiol levels within normal range.
      CONCLUSION: Complete aromatase deficiency provides an excellent model of how
      ovarian and uterine development in relation to E2, LH, FSH and inhibin B feedback
      progresses from infancy to adolescence.

PMID- 25585548
TI  - Are climacteric complaints associated with risk factors of cardiovascular disease
      in peri-menopausal women?
AB  - Recent studies indicate that metabolic risk for cardiovascular disease is
      increased in post-menopausal women suffering from disturbances, such as hot
      flushes. In order to evaluate whether this is also true in peri-menopausal women,
      we performed an observational study on 590 peri-menopausal women of an outpatient
      center at a University Hospital. Each cardiovascular risk factor, such as blood
      pressure, fasting glucose, fasting lipids and the 10-year risk for cardiovascular
      disease was tested for its relation to climacteric complaints. Greene's
      climacteric scale, and its subscales were used to evaluate climacteric symptoms.
      Analyses were corrected for confounders derived by personal history and
      anthropometric measures. When corrected for confounders, Greene's score was a
      positive determinant of triglycerides (R(2 )= 0.249; p = 0.0001),
      triglycerides/HDL-cholesterol (R(2 )= 0.316; p = 0.0001), glucose (R(2 )= 0.101;
      p = 0.0003), and the 10-year risk for cardiovascular disease, calculated by the
      Framingham formula (R(2 )= 0.081; p = 0.0001). Greene's vasomotor sub-score was
      an independent determinant of LDL-cholesterol (R(2 )= 0.025; p = 0.01), and
      LDL/HDL-cholesterol (R(2 )= 0.143; p = 0.0001), while Greene's depression sub
      score was a negative determinant of HDL-cholesterol (R(2 )= 0.179; p = 0.0001).
      The data also indicate that in peri-menopausal women, menopausal symptoms
      evaluated by a validated climacteric scale are associated with biochemical risk
      factors for atherosclerosis and cardiovascular disease. 

PMID- 25585549
TI  - The dynamic changes of anti-Mullerian hormone and inhibin B during controlled
      ovarian hyperstimulation in decreased ovarian reserve women and the effect on
      clinical outcome.
AB  - OBJECTIVE: To investigate the dynamics of anti-Mullerian hormone (AMH) and
      inhibin B (INHB) levels during controlled ovarian hyperstimulation (COH) in women
      with decreased ovarian reserve (DOR), and assess the effect of these dynamic
      changes on the prediction of clinical outcome in in-vitro fertilization (IVF).
      METHODS: A total of 124 women undergoing IVF cycles were divided into normal
      ovarian reserve (NOR) and DOR groups. AMH and INHB levels were measured in serum
      on menstrual cycle day 2 or 3 (D2/3), day 5 of stimulation (D5), hCG day (D-hCG)
      and follicular fluid (FF) on oocyte retrieval day. RESULTS: Serum AMH levels were
      gradually decreased while INHB levels were gradually increased from D2/3 to D-hCG
      during the COH in both groups. Serum AMH, INHB levels on D2/3 and FF AMH, INHB
      levels were highly positively correlated with AFC and oocytes retrieval.
      Multivariate logistic regression analysis revealed that clinical pregnancy did
      not directly correlate with serum and FF AMH and INHB levels. CONCLUSION: Serum
      AMH and INHB levels were not directly related to clinical pregnancy, dynamic
      serum AMH and IHNB levels were positively correlated with COH outcomes.

PMID- 25585550
TI  - Personal care product preservatives: risk assessment and mixture toxicities with
      an industrial wastewater.
AB  - The aquatic toxicity of eight preservatives frequently used in personal care
      products (PCPs) (iodopropynyl butylcarbamate, bronopol, diazolidinyl urea,
      benzalkonium chloride, zinc pyrithione, propylparaben, triclosan and a mixture of
      methylchloroisothiazolinone and methylisothiazolinone) was assessed by means of
      two different approaches: a battery of bioassays composed of single species tests
      of bacteria (Vibrio fischeri and Pseudomonas putida) and protozoa (Tetrahymena
      thermophila), and a whole biological community resazurin-based assay using
      activated sludge. The tested preservatives showed considerable toxicity in the
      studied bioassays, but with a marked difference in potency. In fact, all biocides
      except propylparaben and diazolidinyl urea had EC50 values lower than 1 mg L(-1)
      in at least one assay. Risk quotients for zinc pyrithione, benzalkonium chloride,
      iodopropynyl butylcarbamate and triclosan as well as the mixture of the studied
      preservatives exceeded 1, indicating a potential risk for the process performance
      and efficiency of municipal sewage treatment plants (STPs). These four single
      biocides explained more than 95% of the preservative mixture risk in all
      bioassays. Each individual preservative was also tested in combination with an
      industrial wastewater (IWW) from a cosmetics manufacturing facility. The toxicity
      assessment was performed on binary mixtures (preservative + IWW) and carried out
      using the median-effect principle, which is a special case of the concept of
      Concentration Addition (CA). Almost 70% of all experiments resulted in EC50
      values within a factor of 2 of the values predicted by the median-effect
      principle (CI values between 0.5 and 2). The rest of the mixtures whose toxicity
      was mispredicted by CA were assessed with the alternative concept of Independent
      Action (IA), which showed higher predictive power for the biological community
      assay. Therefore, the concept used to accurately predict the toxicity of mixtures
      of a preservative with a complex industrial wastewater depends on degree of
      biological complexity. 

PMID- 25585551
TI  - [The optimal imaging in gynecological oncology].
AB  - In this review we discuss in detail the advantages and the limitations of the
      modern imaging techniques to assess the tumour spread in pelvis, abdomen and
      extraabdominally in patients with newly diagnosed or recurrent gynecological
      cancer. Transvaginal ultrasound and magnetic resonance imaging yield similar
      levels of accuracy when utilised for the diagnosis of gynecological cancer and
      the detection of pelvic spread. Ultrasound is, however, a commonly available, non
      invasive, and inexpensive imaging method that can be carried out without any risk
      or discomfort to the patient. Although increasing evidence shows that
      transabdominal ultrasound is an accurate technique for the detection of intra-
      and retroperitoneal tumour spread, it requires experience, adequate equipment and
      suitable acoustic conditions. Contrast-enhanced computed abdominopelvic
      tomography remains the most commonly used preoperative imaging modality to assess
      abdominal cavity and retroperitoneum for extrapelvic tumour spread. Alternatively
      magnetic resonance imaging can be used in cases of contra-indication of computed
      tomography. If there is suspicion of extraabdominal tumour spread, contrast
      enhanced computed tomography of thorax or positron emission tomography combined
      with computed tomography is used. Positron emission tomography combined with
      computed tomography detects more distant metastases than computed tomography
      alone. Positron emission tomography with computed tomography is, therefore, the
      optimal imaging technique for suspected recurrence, particularly if there is
      suspicion of recurrence but conventional imaging methods have yilded negative
      results or if salvage surgery is planned.

PMID- 25585552
TI  - [Cervical cancer staging - preoperative assessment of tumor extent (a review of
      the most recent ultrasound studies)].
AB  - For treatment planning of cervical cancer it is necessary preoperatively to
      determine the presence and size of residual tumour after the biopsy, the tumour
      topography within the cervix and the parametrial and lymph node status. According
      to current data, ultrasound is comparably accurate with magnetic resonance
      imaging in view of tumour presence and local extent assessment. Ultrasound, if
      compared with the magnetic resonance imaging, does not have known
      contraindications and it is a broadly available diagnostic test. Currently no
      advanced imaging technique exists that can reliably detect infiltrated lymph
      nodes in the clinically early stage of the disease, as it often manifests as
      micrometastatic involvement in non-enlarged lymph nodes. The sensitivity of lymph
      node detection using ultrasound in the early stage is around 40%, but the
      specificity is high (96%). For daily practice, this means that a negative
      ultrasound finding should be always verified by surgical staging based on
      systematic lymphadenectomy, while positive ultrasound finding usually changes the
      treatment strategy.

PMID- 25585553
TI  - [Ultrasonic staging cervical cancer -a proposal for the standard procedure].
AB  - OBJECTIVE: To develop guidelines for the ultrasound examination of cervical
      cancer, including a unified ultrasound terminology. SUBJECT: Original paper.
      SETTING: Gynecological Oncology Center, Department of Obstetrics and Gynecology,
      Masaryk University and General Faculty Hospital Brno, and Gynecological Oncology
      Center, Department of Obstetrics and Gynecology, Charles University in Prague -
      First Faculty of Medicine and General Faculty Hospital Prague. SUBJECT AND
      METHOD: The standard diagnostic algo-rithm for examination of cervical cancer in
      oncogynecology centers in the Czech Republic is based on published studies, own
      experience (Oncogynecological Center, Department of Gynecology and Obstetrics,1st
      Medical Faculty, Charles University) and the experiences of a group of
      ultrasonographers involved in the grant project IGA MZ CR NT13070 focused on the
      implementation of an oncogynecological ultrasound into clinical practice.
      Standard ultrasound examination includes two-dimensional real-time ultrasound
      examination (sagittal and transverse views). Transrectal or transvaginal
      ultrasound examination is combined with transabdominal ultrasound. Prerequisites
      are quality ultrasound equipment, a high frequency microconvex linear probe and
      abdominal convex and linear probe. The examination is performed by an experienced
      sonographer (level 2 or 3 according to the recommendations of the Ultrasound
      division of the Czech Society of Obstetrics and Gynecology and the Czech Society
      of Ultrasound in Obstetrics and Gynecology). Intravenous administration of
      contrast material or three-dimensional ultrasound examination do not influence
      accuracy of the examination and is not a prerequisite. CONCLUSION: Based on the
      consensus of experienced sonographers and a review of the literature, guidelines
      were created for ultrasound staging of cervical cancer.

PMID- 25585554
TI  - [Endometrial cancer - preoperative identification of low and high risk
      endometrial cancer (a review of the most recent ultrasound studies)].
AB  - Despite the high resolution of ultrasound or magnetic resonance imaging and
      modern bioptic approaches, diagnostic error of preoperative staging is around
      20%. The preoperative staging is focused to differentiate low risk (< 50%
      myometrial invasion, histological grade 1 and 2, endometrioid cancer, no cervical
      invasion) or high risk endometrial cancer (all others). Preoperative biopsy tends
      to underestimate the tumour histotype and grading in 20% of cases. Therefore, the
      sonomorphological and Doppler pattern have been identified that can
      preoperatively alert us to the presence of low or high risk endometrial cancer.
      With discrepancy between preoperative ultrasound tumour characteristics and
      results of endometrial biopsy a supplementary intraoperative frozen section of
      uterus is recommended. Ultrasound examination performed by an experienced
      sonographer is accurate in most cases but tends to overestimate myometrial
      invasion and underestimate cervical stromal invasion. Based on the identification
      of factors that significantly affected the accuracy of ultrasound, it was
      recommended to restrict evaluation to sonomorphological tumour parameters within
      the preoperative tumour staging. This is in response to the tendency of
      ultrasound experts with knowledge of the clinical data of patients, and
      prognostic parameters of the disease who have encountered adverse tumour
      characteristics through ultrasound (e.g. inhomogeneous, hypo- or isoechogenous
      tumor with high tumour perfusion) to 'intuitively overestimate the stage of the
      disease and conversely. The attempts to restrict the assessment of tumour
      invasion to those parameters that are easily and objectively evaluated has not so
      far proved effective. A promising objective parameter seems to be the minimum
      distance between the tumour and uterine serosa. When this parameter was included
      in the new objective model, the high-risk endometrial cancer was predicted with
      an accuracy similar to subjective assessment of tumour invasion by an expert. The
      preoperative work-up for high-risk endometrial cancer prediction was designed and
      externally validated in order to triage the patients for adequate staging
      surgery. This approach was based on the combination of the results of
      preoperative endometrial biopsy and transvaginal ultrasound and reached the
      similar accuracy as a more complicated approach using a combination of magnetic
      resonance imaging and hysteroscopic-directed biopsies. Both approaches can
      identify eight of 10 women with high-risk of lymph node metastases and spare
      eight of 10 low-risk women extended surgery.

PMID- 25585555
TI  - [Ultrasound staging of endometrial cancer - recommended methodology of
      examination].
AB  - The extent of the staging surgery in cases of histologically proven endometrial
      cancer depends on whether the tumor is of high risk or low risk for extrauterine
      spread and recurrence. There are several significant prognostic factors -
      histological subtype and grade of dediferentiation from preoperative biopsy and
      local stage of uterine involvement based on imaging methods. The depth of
      myometrial invasion and presence of cervical stromal infiltration (local staging)
      can be assessed by ultrasound with the overall accuracy comparable to that of
      magnetic resonance. Transvaginal ultrasound enables to vizualize detailed pelvic
      anatomy and that is why it is considered to be a suitable tool for assessment of
      local stage of endometrial cancer. It is advisable to use the standardized
      terminology defined by International Endometrial Tumor Analysis group (IETA) to
      describe ultrasound findings. The standardized methodology of ultrasound
      preoperative staging examination based on prearranged protocols is recommended.

PMID- 25585556
TI  - [Recommended guidelines of diagnosis for women with an ovarian cyst or tumour].
AB  - Transvaginal ultrasonography is the first-line and best imaging technique for
      characterising adnexal masses preoperatively. The optimal approach is the
      subjective assessment of ultrasound images by experts. An alternative evidence
      based approach to the pre-surgical diagnosis of adnexal tumours is to use simple
      ultrasound rules or logistic regression model LR2 developed by the International
      Ovarian Tumor Analysis (IOTA) group. Their test performance matches subjective
      assessment by experienced examiners and should be adopted as the principal test
      to characterize masses as benign or malignant. Measurements of serum CA 125 are
      not necessary for characterization of ovarian pathology in premenopausal women
      and are unlikely to improve the performance of experienced ultrasound examiners,
      even in the postmenopausal group. However, in postmenopausal patients, serum CA
      125 may play a role as a second-stage test, especially in centers with less
      experienced ultrasound examiners.

PMID- 25585557
TI  - [Ultrasound-guided minimally invasive interventions in gynecologic oncology].
AB  - OBJECTIVE: To present our experience with ultrasound-guided minimally invasive
      bioptic techniques in gynecologic oncology. SUBJECT: Original paper. SETTING:
      Gynecological Oncology Center, Department of Obstetrics and Gynecology, Charles
      University, First Faculty of Medicine and General Faculty Hospital, Prague.
      SUBJECT AND METHOD: Minimally invasive ultrasound-guided biopsy may be done in
      patients with primary inoperable disease, suspicious recurrence of gynecological
      or non-gynecological malignancy or in case of diagnostic uncertainty of pelvic
      tumor origin. CONCLUSION: Ultrasound-guided minimally invasive bio-psy represents
      an accessible and relatively simple method useful in many indications, not only
      in gynecologic oncology.

PMID- 25585558
TI  - [The importance of screening in oncogynecology].
AB  - Cervical cancer can be greatly prevented by the active search for precancerous
      lesions, by the effective screening. The DNA detection of high-risk human
      papillomavirus seems to be suitable primary screening tool, more effective than
      smear for cervical cytology. Organised mass screening for endometrial cancer is
      not held. The reason is very low prevalence of atypical hyperplasia and
      endometrial carcinoma in asymptomatic women and relatively low mortality rate,
      which is not influenced by the detection in asymptomatic stage. It is advisible
      to instruct all women to seek the gynecologist immediately in case of abnormal
      uterine bleeding and to emphasize the health education in population. Optimal
      protocol of the screening for hereditary endometrial malignities is debated
      currently. There is no effective screening for ovarian cancer in general
      population. Firstly, the global prevalence of the disease is low. Secondly, there
      is no screening modality to detect precursor lesions of the majority of malignant
      ovarian tumors (type II). Different strategies are tested as screening for
      hereditary ovarian cancer, but they cannot alternate profylactic surgery
      (bilateral salpingo-oophorectomy).

PMID- 25585559
TI  - [Blood-less Medicine in Gynecologyand Oncogynecology].
AB  - The methods of bloodless medicine are used in many surgical fields. This article
      aims to draw attention to the possible use of these procedures in gynecological
      surgery to reduce the number of transfusions.

PMID- 25585560
TI  - Sink or Night Float: University of British Columbia Radiology Residents'
      Experience With Overnight Call.
AB  - PURPOSE: In July 2012, in response to residents' concerns regarding the impact of
      the traditional 24-hour call system on their personal well-being and educational
      experience, the University of British Columbia Radiology residency program
      adopted a 12-hour night float system. This shift takes place in the context of
      increasing concerns, both across Canada and internationally, about resident well
      being and the impact of prolonged duty hours on patient care. METHODS: An
      anonymous survey was distributed to all 25 postgraduate years 2-5 University of
      British Columbia radiology residents 12 months after the introduction of night
      float. This study sought to solicit residents' feedback about these changes and
      to identify potential future changes to optimize the call system. RESULTS: The
      response rate was 100%; 96% of residents were in favor of continuing with night
      float rather than the traditional call system; 72% of residents reported that
      their judgement was affected secondary to being on night float. Although most
      residents described varying degrees of impairment, the rate of acute
      discrepancies between resident preliminary and attending radiologist final
      reports decreased by more than half, from 2% to less than 1%. CONCLUSIONS: The
      vast majority of our residents were in favor of maintaining the night float call
      system. Night float had a beneficial effect on the resident educational
      experience: by eliminating the pre-call morning and post-call day off rotation,
      residents gained an additional 24 days per year on other clinical rotations.

PMID- 25585561
TI  - Canadian Association of Radiologists Annual Scientific Meetings: How Many
      Abstracts Go on to Publication?
AB  - PURPOSE: To determine the percentage of abstracts presented at the Canadian
      Association of Radiologists (CAR) annual scientific meetings that go on to
      publication. METHODS: Records of previous CAR meetings from the years 2005-2011
      were obtained. An Internet search was performed to determine which abstracts went
      on to publication. Abstracts were assessed according to exhibit category
      (Resident Award Papers), educational institution, publishing journal, and time to
      publication. RESULTS: Of the 402 abstracts presented, 112 (28%) were published.
      Overall, an average of 37% of Radiologists-In-Training Presentations, 34% of
      Scientific Exhibits, and 20% of Educational Exhibits went on to publication. The
      University of British Columbia and University of Ottawa published the largest
      number of abstracts (66 and 62, respectively) from the years 2005-2011. The
      University of Montreal had the largest percentage of abstracts published (42%).
      The range of publishing journals was wide, but the top publisher was the Canadian
      Association of Radiologists Journal (27%). Eighty-three percent of abstracts were
      published within 3 years of being presented. CONCLUSION: In total, 28% of all the
      abstracts presented at the CAR conferences between 2005 and 2011 were published.
      Further exploration into the reasons and barriers for abstracts not being
      published may be a next step in future research.

PMID- 25585562
TI  - A Comparative Study of Four Oral Contrast Agents for Small Bowel Distension with
      Computed Tomography Enterography.
AB  - PURPOSE: To assess the efficacy of a variety of oral contrast agents in obtaining
      small bowel distention for computed tomography (CT) enterography examinations.
      METHODS: A retrospective study was developed to quantitatively assess small bowel
      luminal distension during CT enterography by using 4 contrast agents, which
      included water, Metamucil, polyethylene glycol, and lactulose. A total of 256
      patients were enrolled in the study and included 64 individuals for each oral
      regimen. The widest loop of small bowel in each of 4 quadrants on representative
      coronal images was separately measured for luminal distension. Overall distension
      and the greatest number of "useful" quadrants were evaluated. Overall distension
      was calculated by summing the 4 quadrant values into an overall luminal diameter
      distention score (cm). A "useful" quadrant was defined as having a measurement of
      >=2 cm. Each "useful" quadrant was assigned a score of 1, with values that ranged
      from 0-4. RESULTS: For overall distension, multivariable liner regression
      analysis showed that the lactulose group had a significantly higher overall
      distension value than Metamucil, polyethylene glycol, and water by 0.88, 0.92,
      and 1.63 cm, respectively, with 95% confidence interval. The categorical
      multivariable logistic regression analysis showed that the lactulose group had
      greater odds of having more "useful" quadrants than the Metamucil, polyethylene
      glycol, and water groups, with odds ratios of 3.51, 2.68, and 9.19, respectively.
      CONCLUSION: Lactulose achieves better small bowel distension for CT enterography
      studies than the other 3 agents and, therefore, is the preferred oral regimen at
      our institution.

PMID- 25585563
TI  - Fabrication of hierarchical Fe3O4@SiO2@P(4VP-DVB)@Au nanostructures and their
      enhanced catalytic properties.
AB  - Hierarchical Fe3O4@SiO2@P(4VP-DVB)@Au nanostructures were prepared in which the
      slightly cross-linked, thin poly(4-vinylpyridine-co-divinylbenzene) (P(4VP-DVB))
      shells were constructed onto Fe3O4@SiO2 nanospheres, followed by in situ
      embedding of gold nanocrystals homogeneously into the P4VP chains. These slightly
      cross-linked chains, easily swollen by the reactants, make the gold nanocrystals
      accessible to the reactants, and the thin shell (about 15 nm) reduces the
      diffusion distance of the reactants to the active gold nanocrystals (about 5 nm),
      thereby enhancing their catalytic activity and utility. At the same time,
      confinement of gold nanocrystals within the P4VP shells prevents their migration
      and coagulation during catalytic transformations. Hence the nanocomposites
      exhibit high activity (up to 4369.5 h(-1) of turnover frequency (TOF)) and
      controllable magnetic recyclability without any significant loss of gold species
      after ten runs of catalysis in the reduction of 4-nitrophenol.

PMID- 25585564
TI  - Design, fabrication, and implementation of a wireless, passive implantable
      pressure sensor based on magnetic higher-order harmonic fields.
AB  - A passive and wireless sensor was developed for monitoring pressure in vivo.
      Structurally, the pressure sensor, referred to as the magneto-harmonic pressure
      sensor, is an airtight chamber sealed with an elastic pressure membrane. A strip
      of magnetically-soft material is attached to the bottom of the chamber and a
      permanent magnet strip is embedded inside the membrane. Under the excitation of
      an externally applied AC magnetic field, the magnetically-soft strip produces a
      higher-order magnetic signature that can be remotely detected with an external
      receiving coil. As ambient pressure varies, the pressure membrane deflects,
      altering the separation distance between the magnetically-soft strip and the
      permanent magnet. This shifts the higher-order harmonic signal, allowing for
      detection of pressure change as a function of harmonic shifting. The wireless,
      passive nature of this sensor technology allows for continuous long-term pressure
      monitoring, particularly useful for biomedical applications such as monitoring
      pressure in aneurysm sac and sphincter of Oddi. In addition to demonstrating its
      pressure sensing capability, an animal model was used to investigate the efficacy
      and feasibility of the pressure sensor in a biological environment. 

PMID- 25585565
TI  - ZnO Nanorods Based Enzymatic Biosensor for Selective Determination of Penicillin.
AB  - In this study, we have successfully demonstrated the fabrication of a biosensor
      based on well aligned single-crystal zinc oxide (ZnO) nanorods which were grown
      on gold coated glass substrate using a low temperature aqueous chemical growth
      (ACG) method. The ZnO nanorods were immobilized with penicillinase enzyme using
      the physical adsorption approach in combination with N-5-azido-2
      nitrobenzoyloxysuccinimide (ANB-NOS) as cross linking molecules. The
      potentiometric response of the sensor configuration revealed good linearity over
      a large logarithmic concentration range from 100 uM to 100 mM. During the
      investigations, the proposed sensor showed a good stability with high sensitivity
      of ~121 mV/decade for sensing of penicillin. A quick electrochemical response of
      less than 5 s with a good selectivity, repeatability, reproducibility and a
      negligible response to common interferents such as Na1+, K1+, d-glucose, l
      glucose, ascorbic acid, uric acid, urea, sucrose, lactose, glycine, penicilloic
      acid and cephalosporins, was observed. 

PMID- 25585566
TI  - Conformational changes of calmodulin on calcium and Peptide binding monitored by
      film bulk acoustic resonators.
AB  - Film bulk acoustic resonators (FBAR) are mass sensitive, label-free biosensors
      that allow monitoring of the interaction between biomolecules. In this paper we
      use the FBAR to measure the binding of calcium and the CaMKII peptide to
      calmodulin. Because the mass of the calcium is too small to be detected, the
      conformational change caused by the binding process is measured by monitoring the
      resonant frequency and the motional resistance of the FBAR. The resonant
      frequency is a measure for the amount of mass coupled to the sensor while the
      motional resistance is influenced by the viscoelastic properties of the
      adsorbent. The measured frequency shift during the calcium adsorptions was found
      to be strongly dependent on the surface concentration of the immobilized
      calmodulin, which indicates that the measured signal is significantly influenced
      by the amount of water inside the calmodulin layer. By plotting the measured
      motional resistance against the frequency shift, a mass adsorption can be
      distinguished from processes involving measurable conformational changes. With
      this method three serial processes were identified during the peptide binding.
      The results show that the FBAR is a promising technology for the label-free
      measurement of conformational changes. 

PMID- 25585567
TI  - John Hughlings Jackson (1835-1911): An adornment to the London Hospital.
AB  - John Hughlings Jackson was associated with the London Hospital as a Lecturer and
      Physician for nearly 40 years while also on the staff at The National Hospital,
      Queen Square. His experience at the two hospitals was complementary; sometimes, a
      patient would be exchanged between the two hospitals. At the London Hospital, he
      was especially revered by students, colleagues and even by the House Governor,
      for his knowledge and his contributions to neurology. His ideas helped to resolve
      the chaotic contemporary understanding of neurological phenomena into a coherent
      whole, determining the direction of future neurological research in the following
      century. His life and work was supported and strengthened by the help and
      friendship of his colleagues at the London Hospital, especially Sir Jonathan
      Hutchinson. 

PMID- 25585569
TI  - New targets for obesity pharmacotherapy - developing anti-obesity drugs that do
      not necessarily produce weight loss.

PMID- 25585568
TI  - NUSAP1 expression is upregulated by loss of RB1 in prostate cancer cells.
AB  - BACKGROUND: Overexpression of NUSAP1 is associated with poor prognosis in
      prostate cancer, but little is known about what leads to its overexpression.
      Based on previous observations that NUSAP1 expression is enhanced by E2F1, we
      hypothesized that NUSAP1 expression is regulated, at least in part, by loss of
      RB1 via the RB1/E2F1 axis. METHODS: Using Significance Analysis of Microarrays,
      we examined RB1, E2F1, and NUSAP1 transcript levels in prostate cancer gene
      expression datasets. We compared NUSAP1 expression levels in DU145, LNCaP, and PC
      3 prostate cancer cell lines via use of cDNA microarray data, RT-qPCR, and
      Western blots. In addition, we used lentiviral expression constructs to knockdown
      RB1 in prostate cancer cell lines and transient transfections to knockdown E2F1,
      and investigated RB1, E2F1, and NUSAP1 expression levels with RT-qPCR and Western
      blots. Finally, in DU145 cells or PC-3 cells that stably underexpress RB1, we
      used proliferation and invasion assays to assess whether NUSAP1 knockdown affects
      proliferation or invasion. RESULTS: NUSAP1 transcript levels are positively
      correlated with E2F1 and negatively correlated with RB1 transcript levels in
      prostate cancer microarray datasets. NUSAP1 expression is elevated in the RB1
      null DU145 prostate cancer cell line, as opposed to LNCaP and PC-3 cell lines.
      Furthermore, NUSAP1 expression increases upon knockdown of RB1 in prostate cancer
      cell lines (LNCaP and PC-3) and decreases after knockdown of E2F1. Lastly,
      knockdown of NUSAP1 in DU145 cells or PC-3 cells with stable knockdown of RB1
      decreases proliferation and invasion of these cells. CONCLUSION: Our studies
      support the notion that NUSAP1 expression is upregulated by loss of RB1 via the
      RB1/E2F1 axis in prostate cancer cells. Such upregulation may promote prostate
      cancer progression by increasing proliferation and invasion of prostate cancer
      cells. NUSAP1 may thus represent a novel therapeutic target.

PMID- 25585570
TI  - Predictors of weight loss maintenance and attrition during a 6-month dietary
      intervention period: results from the DiOGenes study.
AB  - There is a need to develop tools to predict individual weight loss maintenance
      and attrition prognosis. We aimed to identify predictors of weight loss
      maintenance outcome and attrition in subjects from eight European countries in
      the DiOGenes project. A total of 932 overweight/obese subjects (body mass index:
      27-42 kg m(-2) ) were enrolled in an 8-week low-calorie diet (LCD). The 776
      subjects (83%) who achieved at least 8% reduction in their initial body weight
      were randomized into five dietary arms varying in protein content and glycemic
      index for a 6-month weight maintenance period. Baseline characteristics, weight
      loss at weeks 1, 3 and 8 of LCD were assessed as predictors of weight loss
      maintenance and attrition using multivariate regression and correlation models.
      The multivariate model showed that the 6-month weight loss maintenance was
      predicted by: 7.889 - 0.343 * weight loss at week 3 + 1.505 * weight loss at week
      8 + 2.422 * gender (0 = male and 1 = female gender) (R(2)  = 51%, P = 0.0001). A
      greater weight loss at week 8 was associated with a lower attrition during the
      subsequent 6-month dietary intervention period (OR = 0.92, 95% CI: 0.88-0.97, P =
      0.001). Furthermore, the men showed an increased likelihood for attrition during
      the dietary intervention period (OR = 1.54, 95% CI: 1.07-2.20, P = 0.02). A
      greater weight loss during 8 weeks of LCD and female gender predict better 6
      month weight maintenance of weight loss, whereas the baseline characteristics did
      not predict outcome. Attrition could be strongly predicted by gender and weight
      loss during LCD. 

PMID- 25585571
TI  - Reduction of misclassification rates of obesity by body mass index using dual
      energy X-ray absorptiometry scans to improve subsequent prediction of per cent
      fat mass in a Caucasian population.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: *  Body mass index (BMI) is not
      accurate in the classification of excess body fat, failing to identify as many as
      half of individuals with excess per cent fat mass. *  Normal-weight obesity,
      which goes undiagnosed when BMI is the only measure of adiposity utilized, has
      been shown to be associated with an increased risk of cardiovascular
      comorbidities and mortality. *  Dual-energy X-ray absorptiometry (DXA) is an
      accurate and relatively inexpensive method for indirect assessment of body
      composition. WHAT THIS STUDY ADDS: *  The formulae developed allow the clinician
      to utilize information from one baseline DXA scan to calculate a patient's per
      cent fat mass with a future change in weight, thus allowing the clinician to more
      accurately determine whether and when an individual patient should be classified
      as obese and thus be managed appropriately. *  The formulae developed enable the
      clinician to calculate a patient-specific BMI treatment goal, below which the
      patient would no longer meet the per cent fat mass criteria for obesity. SUMMARY:
      Recognition is increasing for the errors of body mass index (BMI) in
      classification of excess body fat. Dual-energy X-ray absorptiometry (DXA) is
      accurate to assess body fat mass per cent (%FM), but is underutilized clinically.
      We examined the prevalence of obesity misclassification by BMI in comparison to
      body %FM by DXA scanning, and whether there is a time-stable individual relation
      between the %FM and the BMI in patients scanned several times. We aimed to
      develop a formula where, based on a single DXA scan, %FM could be predicted
      following a change in weight, and a patient-specific BMI threshold could be
      calculated (BMIT ), above which the patient would be obese by %FM criteria. Data
      were collected from individuals who had a DXA scan as part of a nutritional
      research study at the University of Copenhagen. BMI incorrectly classified 48/329
      (14.6%) of men and 52/589 (8.8%) of women. The majority of men with BMI 25-27 kg
      m(-2) and women with BMI 24-26 kg m(-2) were misclassified. Using multiple scan
      data (189 men, 311 women) and calculating the patient-specific constant C = (1 -
      %FM/100)(3/2)  * BMI from baseline BMI and %FM, misclassification rates were
      halved for both genders when a personal threshold, BMIT , was used ([BMIT  =
      C/(0.75)(3/2) ] for men and [BMIT  = C/(0.65)(3/2) ] for women). We conclude that
      simple formulae allow evaluation of fatness of individual patients more
      accurately than BMI, with the use of one baseline DXA scan, and enable the
      establishment of patient-specific obesity treatment targets in clinical practice.

PMID- 25585572
TI  - Assessment of obesity beyond body mass index to determine benefit of treatment.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: *  Weight or weight loss per se may not
      indicate health status or health benefit. *  There is no gold standard for
      assessing which patients would benefit most from weight-loss interventions. * 
      The King's Criteria is one of several recently proposed obesity classification
      systems. WHAT THIS STUDY ADDS: *  The King's Criteria can capture health problems
      related to obesity and health benefits after weight loss. *  The King's Criteria
      is a reproducible scoring system. *  Using the King's Criteria may help shift the
      focus of patients and clinicians from weight loss to health gain. SUMMARY: Body
      mass index (BMI) alone does not reflect health status in individuals. The King's
      Obesity Staging Criteria is a clinical tool for the assessment of patients with
      complex obesity. We assessed the performance of a modified version of the King's
      Criteria by scoring 144 obese patients before and 1 year after bariatric surgery.
      We also evaluated inter-observer variability by having 11 clinicians score the
      same 12 patients. The King's Obesity Staging Criteria comprise nine health
      domains: Airways, Body mass index, Cardiovascular disease, Diabetes, Economic
      complications, Functional limitations, Gonadal axis, Health status (perceived),
      and body Image. For each domain, a person's health is assigned a score of 0
      ('normal health'), 1 ('at risk'), 2 ('established disease') or 3 ('advanced
      disease'). The patient's mean BMI decreased from 48 +/- 7 to 37 +/- 7 kg m(-2)
      post surgery. Before surgery, 84% of patients were either in stage 2
      ('established disease') or stage 3 ('advanced disease') for one or more domains
      other than BMI. The modified King's Criteria showed significant health
      improvements after surgery, with a higher proportion of patients scored in stage
      0 ('normal health') within each health domain (P < 0.001 for all). Observers
      assigned the same score in >75% of cases for all domains except Health status
      perceived (71%) and body Image (65%). In conclusion the King's Criteria captured
      morbidity in obese patients and health gains after weight loss. Different
      clinicians mostly assigned similar scores. The King's Criteria is a clinical tool
      that may help shift the focus of patients and clinicians towards improving health
      and not only losing weight. REGISTRATION NUMBER: NCT01112228
      (http://www.clinicaltrials.gov).

PMID- 25585573
TI  - Helping young weight controllers develop healthy obsessions: preliminary test of
      the Healthy Obsession Model.
AB  - The Healthy Obsession Model posits that successful weight controllers must
      develop a preoccupation with the planning and execution of target behaviours,
      including eating on programme, consistent activity and self-monitoring. When
      barriers emerge, committed weight controllers are expected to feel distressed
      (e.g. anxious or frustrated), which should motivate them to reinstate these
      behaviours. This study investigated the effects on moods of sudden withdrawal of
      self-monitoring among obese adolescents within an immersion treatment programme.
      Fifty-five (55% female) adolescents participated in a weight loss camp and
      received four weekly cognitive-behaviour therapy sessions focused on maximizing
      commitment to programme behaviours. During the fourth week, campers and staff
      completed daily mood ratings using the Positive and Negative Affect Schedule.
      After 3 d of ratings, campers' self-monitoring journals were removed without
      warning for 1 d. As expected, journal removal resulted in decreased positive
      affect for the campers, according to staff ratings. Also in accord with
      hypotheses, campers who demonstrated heightened commitment to the programme based
      on higher levels of activity and more writing in their journals reacted more
      negatively to the withdrawal of the opportunity to self-monitor. Mood ratings by
      campers did not show the effects hypothesized by the Healthy Obsession Model.
      These results provide preliminary support for the Healthy Obsession Model by
      showing some of the anticipated negative reactions to the removal of access to
      self-monitoring, especially among those who demonstrated strong commitments to
      the process. 

PMID- 25585574
TI  - Do as I do? Prospects for parental participation 1.5 years after immersion
      treatment for adolescent obesity.
AB  - This study compared successful with unsuccessful participants and their mothers
      1.5 years following completion of an immersion programme for the treatment of
      adolescent obesity. Teenagers (M age = 14.5; 69.5% female) participated in a 4-
      to 8-week therapeutic camp; those who continued losing weight 1.5 years post-camp
      were identified as 'Losers'; those who regained weight were considered 'Gainers'.
      Twenty-six Loser campers, 23 Gainer campers and all mothers were interviewed
      about their current weights and lifestyle habits. Losers' and Gainers' mothers
      both reported losing weight significantly. Relative to Gainer mothers, however,
      Loser mothers reported 26% fewer high-fat foods in the house and greater
      likelihood of self-monitoring. Loser campers, relative to Gainer campers,
      reported self-monitoring more consistently; using trainers more frequently; and
      consuming fewer calories and less fat. Gainer campers also reported a tendency to
      use family therapy more than Loser families. The Loser campers reported following
      the dictates of the programme more than the Gainer campers, as expected. One
      striking and unique finding, however, was that Gainer mothers seemed to follow
      the programme for themselves as much as Loser mothers. Apparently for some
      participants in immersion treatment (like the Loser campers in this study),
      parents who participate fully may promote sustained success; for other adolescent
      weight controllers (like the present Gainer campers), having 'Do as I do' mothers
      clearly does not guarantee sustained changes in lifestyle for the teenagers. A
      hypothesis based on these results is that additional cognitive-behaviour therapy
      subsequent to immersion may be useful for this latter group. 

PMID- 25585575
TI  - Decisions about weight management: a synthesis of qualitative studies of obesity.
AB  - There is a high non-attendance and dropout attrition from weight management
      interventions for adults with obesity. Patient dissatisfaction with consultations
      involving decisions about interventions may be a factor. A systematic review was
      undertaken of qualitative studies reporting perceptions, experiences, contexts
      and influences for adults facing, or reflecting on, weight management. The aim
      was to synthesize a generic model of influences on decision-making about weight
      management for adult patients. Electronic database and hand searches identified
      29 qualitative studies involving 1387 participants (mean age 45.3 years; mean BMI
      37.1 kg m(-2) ; 79.9% women). Seven overarching themes were inductively derived
      from extracted data spanning: cultural identity; social structures such as
      gender; responses to obesity stigma; previous weight loss experiences; personal
      motivators and barriers; social support; and practical resources. A model is
      presented in the paper. Improving decisions about weight management requires
      attention to how diffuse cultural and psycho-social factors, such as obesity
      stigma, influence patient choices. Reflection on experiences of previous attempts
      at weight loss is also essential, as are practical resource factors -
      particularly for less affluent groups. Considering these factors along with more
      established theories of individual psychological motivations and barriers may
      help to improve initial participation and retention within interventions. 

PMID- 25585576
TI  - A synthesis of qualitative research on overweight and obese people's views and
      experiences of weight management.
AB  - The effectiveness of existing weight management programmes may be improved by
      understanding overweight and obese people's perceptions of the reasons for
      successful and unsuccessful weight management. Many qualitative studies have
      investigated overweight and obese adults' experiences with weight management.
      This paper presents findings of a meta-ethnography that synthesized 17
      qualitative studies of overweight and obese adults' weight management
      experiences, principally in the context of behavioural weight management
      programmes. Twelve themes were derived describing factors that overweight and
      obese people identify as relevant to weight management: health concerns,
      expectations towards weight management, attributions for weight gain,
      psychological barriers, psychological facilitators, self-perception and body
      image, stigmatization, socio-cultural factors, environmental barriers,
      environmental facilitators, experiences with weight management programmes and
      positive outcomes of programme participation. Interventions that address all of
      the modifiable factors identified in this review are likely to appear credible to
      participants and will engage with the intra- and extra-individual factors that
      they perceive as affecting their weight management efforts. 

PMID- 25585577
TI  - The measurement of maternal obesity: can we do better?

PMID- 25585578
TI  - FBH1 influences DNA replication fork stability and homologous recombination
      through ubiquitylation of RAD51.
AB  - Unscheduled homologous recombination (HR) can lead to genomic instability, which
      greatly increases the threat of neoplastic transformation in humans. The F-box
      DNA helicase 1 (FBH1) is a 3'-5' DNA helicase with a putative function as a
      negative regulator of HR. It is the only known DNA helicase to contain an F-box,
      suggesting that one of its functions is to act as a ubiquitin ligase as part of
      an SCF (SKP1, CUL1 and F-box) complex. Here we report that the central player in
      HR, RAD51, is ubiquitylated by the SCF(FBH1) complex. Expression of an
      ubiquitylation-resistant form of RAD51 in human cells leads to
      hyperrecombination, as well as several phenotypes indicative of an altered
      response to DNA replication stress. These effects are likely to be mediated by
      the enhanced nuclear matrix association of the ubiquitylation-resistant RAD51.
      These data are consistent with FBH1 acting as a negative regulator of RAD51
      function in human cells. 

PMID- 25585579
TI  - Trajectories of Early Binge Drinking: A Function of Family Cohesion and Peer Use.
AB  - Using the National Longitudinal Study of Adolescent Health, we tested latent
      growth models examining whether the number of friends using alcohol and family
      cohesion were linked with trajectories of binge drinking (N = 3,342) from
      adolescence (average age 15.06) into young adulthood (average age 27.93).
      Adolescents with higher family cohesion had lower rates of binge drinking in
      adolescence (b = -.07, p < .05), while those with more friends drinking alcohol
      were more likely to binge drink in adolescence (b = .51, p < .001), young
      adulthood (b = .22, p < .001), and had increasing trajectories of binge drinking
      across 14 years (b = -.29, p < .001). Clinically, we discuss Multiple-Family
      Group Interventions as a potential approach.

PMID- 25585580
TI  - Mitochondria-targeted antioxidant SkQT1 decreases trauma-induced neurological
      deficit in rat and prevents amyloid-beta-induced impairment of long-term
      potentiation in rat hippocampal slices.
AB  - This study assesses a protective effect of a mitochondria-targeted antioxidant
      SkQT1 (a mixture of 10-(6'-toluquinonyl) decyltriphenylphosphonium and 10-(5'
      toluquinonyl) decyltriphenylphosphonium in proportion of 1.4:1), using an open
      focal trauma model of the rat brain sensorimotor cortex and a model of amyloid
      beta1-42 (Abeta)-induced impairment of hippocampal long-term potentiation (LTP),
      a kind of synaptic plasticity associated with learning and memory. It was found
      that a trauma-induced neurological deficit could be partially improved with daily
      intraperitoneal injections of SkQT1 (250 nmol/kg) for 5 days after the trauma.
      Neither an analog of SkQT1 without thymoquinone (C12TPP) nor original
      thymoquinone without a cation residue was effective to improve such conditions.
      In the SkQ molecule, the phosphonium cation can be replaced by the rhodamine 19
      cation, with the SkQTR1 being still active in the treatment of the neurological
      deficit. Application of 200 nM Abeta to rat hippocampal slices impaired the
      induction of LTP in the hippocampal CA1 pyramidal layer. A single intraperitoneal
      injection of SkQT1 (250 nmol/kg body weight) made 24 h before the slice
      preparation prevented the harmful effect of Abeta on the LTP. Thus mitochondria
      targeted antioxidants, containing thymoquinone, have neuroprotective properties. 

PMID- 25585581
TI  - Severe asthma: definition, diagnosis and treatment.
AB  - BACKGROUND: A minority of patients with asthma have uncontrolled or partially
      controlled asthma despite intensive treatment. These patients present a special
      challenge because of the extensive diagnostic evaluation that they need,
      insufficient evidence regarding personalized treatments, and their high
      consumption of health-care resources. METHODS: The definition, diagnosis, and
      treatment of severe asthma are presented on the basis of a selective literature
      review and the authors' clinical experience. RESULTS: Severe asthma is present,
      by definition, when adequate control of asthma cannot be achieved by high-dose
      treatment with inhaled cortico - steroids and additional controllers (long-acting
      inhaled beta 2 agonists, montelukast, and/or theophylline) or by oral
      corticosteroid treatment (for at least six months per year), or is lost when the
      treatment is reduced. Before any further treatments are evaluated, differential
      diagnoses of asthma should be ruled out, comorbidities should be treated,
      persistent triggers should be eliminated, and patient adherence should be
      optimized. Moreover, pulmonary rehabilitation is recommended in order to
      stabilize asthma over the long term and reduce absences from school or work. The
      additional drugs that can be used include tiotropium, omalizumab (for IgE
      mediated asthma), and azithromycin (for non-eosinophilic asthma). Antibodies
      against interleukin-5 or its receptor will probably be approved soon for the
      treatment of severe eosinophilic asthma. CONCLUSION: The diagnosis and treatment
      of severe asthma is time consuming and requires special experience. There is a
      need for competent treatment centers, continuing medical education, and research
      on the prevalence of severe asthma.

PMID- 25585582
TI  - Chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) results from
      inadequate recanalization of the pulmonary circulation after pulmonary
      thromboembolism. Its 2-year prevalence is 1-4% . If untreated, patients with
      CTEPH have a mean life expectancy of less than three years. Fortunately, a number
      of effective treatments are now available. METHODS: This review is based on a
      selective search of PubMed for pertinent articles published from 1980 to 2014.
      RESULTS: The gold-standard test for the exclusion of CTEPH is perfusion
      scintigraphy: the predictive value of a negative test is nearly 100% . On the
      other hand, confirmation of a positive diagnosis for treatment planning requires
      right-heart catheterization and pulmonary angiography. The treatment of first
      choice for CTEPH is surgical pulmonary endarterectomy (PEA), with which about 70%
      of patients can be cured. The perioperative mortality of this procedure in
      experienced centers is now 2-4% . Thirty to 50% of all patients with CTEPH are
      considered inoperable; for these patients, and for patients with persistent
      pulmonary hypertension after PEA, the drug riociguat was introduced in Germany in
      2014 (the first drug specifically introduced for the treatment of CTEPH). There
      is also a new interventional treatment option for inoperable patients-pulmonary
      balloon angioplasty, which is currently being performed in a small number of
      centers. CONCLUSION: The timely diagnosis of CTEPH, followed by referral to a
      specialized center, is now more important than ever, because treatment options
      are now available for nearly all of the forms in which this disease can manifest
      itself.

PMID- 25585583
TI  - Drug treatments for pruritus in adult palliative care.
AB  - BACKGROUND: Pruritus is a rare but troublesome symptom in palliative-care
      patients with a variety of underlying diseases. The pharmacotherapy of pruritus
      is often off-label, and an evidence-based evaluation is needed. METHODS: A
      Cochrane Review published in 2013 was updated with a systematic literature search
      up to January 2014. Randomized and controlled trials (RCTs) with adult palliative
      care patients were included. RESULTS: In the 43 RCTs that were analyzed, three of
      which were more recent than the Cochrane Review, 8 clinically relevant active
      substances were investigated in a total of 19 RCTs. Effective drugs for pruritus
      in palliative-care patients included paroxetine for pruritus of diverse origins
      (1 RCT; strong effect) and indomethacin for HIV-induced prutitus (1 RCT; median
      effect = moderate reduction). Effective drugs for pruritus in uremia were
      gabapentin (2 RCTs; strong effect), nalfurafin (3 RCTs; moderate effect),
      naltrexone (3 RCTs; heterogeneous effects, ranging from weak to strong), and
      cromoglicic acid (2 RCTs; moderate to strong effect). Effective drugs for
      cholestatic pruritus were rifampicin (3 RCTs; moderate effect), flumecinol (2
      RCTs; weak to moderate effect), and naltrexone (2 RCTs; moderate to strong
      effect). Undesired effects were most common with naltrexone (dizziness: 0% -50% ,
      nausea: 0% -50% ) and nalfurafin (nasopharyngitis: 8% -12% , insomnia: 7% -15%).
      CONCLUSION: In view of the diverse etiologies of pruritus in palliative-care
      patients, careful consideration should be given to the choice of drug used to
      treat it. The substances listed here have moderate to strong antipruritic effects
      and merit further study in RCTs of high methodological quality.

PMID- 25585584
TI  - Overexpression of PGC-1alpha enhances cell proliferation and tumorigenesis of
      HEK293 cells through the upregulation of Sp1 and Acyl-CoA binding protein.
AB  - Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha),
      a coactivator interacting with multiple transcription factors, regulates several
      metabolic processes. Although recent studies have focused on the role of PGC
      1alpha in cancer, the underlying molecular mechanism has not been clarified.
      Therefore, we evaluated the role of PGC-1alpha in cell proliferation and
      tumorigenesis using human embryonic kidney (HEK)293 cells and colorectal cancer
      cells. We established stable HEK293 cell lines expressing PGC-1alpha and examined
      cell proliferation, anchorage-independent growth, and oncogenic potential
      compared to parental HEK293 cells. To identify the molecular PGC-1alpha targets
      for increased cell proliferation and tumorigenesis, the GeneFishingTM DEG
      (differentially expressed genes) screening system was used. Western blot analysis
      and immunofluorescence staining were performed for a regulated gene product to
      confirm the results. Forced expression of PGC-1alpha in HEK293 cells promoted
      cell proliferation and anchorage-independent growth in soft agar. In addition,
      HEK293 cells that highly expressed PGC-1alpha showed enhanced tumor formation
      when subcutaneously injected into the bilateral flanks of immunodeficient mice.
      The results of the GeneFishing DEG screening system identified one upregulated
      gene (Acyl-CoA binding protein; ACBP). Real-time RT-PCR, western blot analysis,
      and immunofluorescence staining showed that ACBP was markedly increased in HEK293
      cells stably overexpressing PGC-1alpha (PGC-1alpha-HEK293 cells) compared to
      those expressing an empty vector. In PGC-1alpha, ACBP, and specificity protein 1
      (Sp1) siRNA knockdown experiments in PGC-1alpha-HEK293 and SNU-C4 cells, we also
      observed inhibition of cell proliferation, reduced expression of antioxidant
      enzymes, and increased H2O2-induced reactive oxygen species production and
      apoptosis. These findings suggest that PGC-1alpha may promote cell proliferation
      and tumorigenesis through upregulation of ACBP. We provide evidence that
      increased Sp1 expression might contribute to enhanced ACBP expression by PGC
      1alpha. The current results also suggest that PGC-1alpha, whose expression is
      related to enhanced cell proliferation and tumorigenesis, may be a good candidate
      molecular target for cancer therapy.

PMID- 25585586
TI  - The proteome of cblC defect: in vivo elucidation of altered cellular pathways in
      humans.
AB  - Methylmalonic acidemia with homocystinuria, cobalamin deficiency type C (cblC)
      (MMACHC) is the most common inborn error of cobalamin metabolism. Despite a
      multidrug treatment, the long-term follow-up of early-onset patients is often
      unsatisfactory, with progression of neurological and ocular impairment. Here, the
      in-vivo proteome of control and MMACHC lymphocytes (obtained from patients under
      standard treatment with OHCbl, betaine, folate and L-carnitine) was
      quantitatively examined by two dimensional differential in-gel electrophoresis
      (2D-DIGE) and mass spectrometry. Twenty three proteins were found up-regulated
      and 38 proteins were down-regulated. Consistent with in vivo studies showing
      disturbance of glutathione metabolism, a deregulation in proteins involved in
      cellular detoxification, especially in glutathione metabolism was found. In
      addition, relevant changes were observed in the expression levels of proteins
      involved in intracellular trafficking and protein folding, energy metabolism,
      cytoskeleton organization and assembly. This study demonstrates relevant changes
      in the proteome profile of circulating lymphocytes isolated from treated cblC
      patients. Some results confirm previous observations in vivo on fibroblast, thus
      concluding that some dysregulation is ubiquitous. On the other hand, new findings
      could be tissue-specific. These observations expand our current understanding of
      the cblC disease and may ignite new research and therapeutic strategies to treat
      this disorder. 

PMID- 25585587
TI  - [Innovative techniques in atrial fibrillation therapy].
AB  - Pulmonary vein isolation (PVI) is the established cornerstone in most catheter
      based ablation treatment strategies for atrial fibrillation (AF); however, it is
      still a challenge to create contiguous, transmural and permanent ablation lesions
      using radiofrequency current in combination with three-dimensional mapping
      systems. To overcome these limitations, innovative spiral mapping and ablation
      catheters as well as balloon-based ablation catheters incorporating alternative
      energy sources, such as cryoenergy and laser were developed and evaluated and
      have proved their potential for safe and clinically effective PVI. In addition,
      novel ablation strategies, such as identification and ablation of AF-inducing
      foci and/or AF-perpetuating rotors using either endocardial or epicardial mapping
      systems were introduced and are currently under clinical evaluation. The
      identification and modulation of atrial ganglionic plexi (GP) and, therefore, of
      the autonomous nervous system is another additive ablation approach which
      requires further clinical evaluation. 

PMID- 25585588
TI  - [Interventional treatment for paroxysmal atrial fibrillation : which is the
      optimal ablation approach?].
AB  - Atrial fibrillation is one of the most common arrhythmias and effects probably
      more than 35 million people worldwide. The incidence in patients older than 70
      years of age is as high as 10%. One can expect that according to our demographic
      development this entity will be increasingly important within the next years and
      decades. Along with the well know and established but at the same time limited
      opportunities of pharmacological treatment option of this arrhythmia, catheter
      ablation has evolved as a safe and effective treatment option. Electrical
      isolation of the pulmonary vein remains the standard of care and results in
      success rates as high as 80% using modern ablation strategies. Optimization of
      procedural and ablation techniques has lead to this high success rates. Different
      energy sources are available, such as radiofrequency, cryoenergy and laser are
      widely used today to treat patients with symptomatic atrial fibrillation. PV
      isolation using a so called "single-shot" ablation approach has shown to be
      effective with a reduced requirement of periprocedural resources and therefore
      resulting in wider application of this treatment not only in specialized
      electrophysiological centers. The rapid development in this field leads to the
      question which approach can be used as the most likely to result in the highest
      success and least complication rates. This question will be addressed in the
      following manuscript. 

PMID- 25585589
TI  - Influence of step length and landing pattern on patellofemoral joint kinetics
      during running.
AB  - Elevated patellofemoral joint kinetics during running may contribute to
      patellofemoral joint symptoms. The purpose of this study was to test for
      independent effects of foot strike pattern and step length on patellofemoral
      joint kinetics while running. Effects were tested relative to individual steps
      and also taking into account the number of steps required to run a kilometer with
      each step length. Patellofemoral joint reaction force and stress were estimated
      in 20 participants running at their preferred speed. Participants ran using a
      forefoot strike and rearfoot strike pattern during three different step length
      conditions: preferred step length, long (+10%) step length, and short (-10%) step
      length. Patellofemoral kinetics was estimated using a biomechanical model of the
      patellofemoral joint that accounted for cocontraction of the knee flexors and
      extensors. We observed independent effects of foot strike pattern and step
      length. Patellofemoral joint kinetics per step was 10-13% less during forefoot
      strike conditions and 15-20% less with a shortened step length. Patellofemoral
      joint kinetics per kilometer decreased 12-13% using a forefoot strike pattern and
      9-12% with a shortened step length. To the extent that patellofemoral joint
      kinetics contribute to symptoms among runners, these running modifications may be
      advisable for runners with patellofemoral pain. 

PMID- 25585591
TI  - A simple infrared-augmented digital photography technique for detection of
      pupillary abnormalities.
AB  - BACKGROUND: The purpose of the study was to describe a simple infrared
      photography technique to aid in the diagnosis and documentation of pupillary
      abnormalities. METHODS: An unmodified 12-megapixel "point and shoot" digital
      camera was used to obtain binocular still photos and videos under different light
      conditions with near-infrared illuminating frames. The near-infrared light of 850
      nm allows the capture of clear pupil images in both dim and bright light
      conditions. It also allows easy visualization of the pupil despite pigmented
      irides by augmenting the contrast between the iris and the pupil. RESULTS: The
      photos and videos obtained illustrated a variety of pupillary abnormalities using
      the aforementioned technique. CONCLUSIONS: This infrared-augmented photography
      technique supplements medical education, and aids in the more rapid detection,
      diagnosis, and documentation of a wide spectrum of pupillary abnormalities. Its
      portability and ease of use with minimal training complements the education of
      trainees and facilitates the establishment of difficult diagnoses.

PMID- 25585590
TI  - Scrutinizing calcium flux oscillations in T lymphocytes to deduce the strength of
      stimulus.
AB  - The capture and activation of individual T cells on functionalised surfaces
      enables real-time analyses of the magnitude and rhythm of intracellular calcium
      release. Application of Haarlet transformations generate a calcium flux
      'threshold', with the frequency of the 'threshold crossings' correlating with the
      strength of the original T cell stimulus. These findings represent a new method
      to evaluate graduations in T cell activation in real time, and at a single-cell
      level. 

PMID- 25585593
TI  - Data interpretation: deciphering the biological function of Type 2 diabetes
      associated risk loci.
AB  - AIMS: Type 2 diabetes (T2D) is a complex multifactorial disorder with more than
      40 loci associated with disease susceptibility. Most of these genome-wide
      significant loci reside in noncoding regions, it is important to decipher the
      potential regulatory function of these variants and to differentiate between true
      and tag signals. Nowadays, databases are being developed to study and predict the
      function of these associated variants, and RegulomeDB is one such database.
      METHODS: We used RegulomeDB to analyze the potential function of the associated
      variants reported in five genome-wide association studies (GWAS) of T2D. RESULTS:
      We investigated the 1,567 single nucleotide polymorphisms (SNPs) with 989 SNPs
      with a score of 1-6. Of those 989 SNPs, only 64 returned with RegulomeDB score <3
      (evidence of regulatory function), and only four of these were GWAS significant
      SNPs (THADA/rs10203174, score = 1b; UBE2E2/rs7612463, score = 2a; ARAP1/rs1552224
      and TP53INP1/rs8996852, score = 2b). But only 63 % of the annotated SNPs showed
      regulatory function that is an important limitation of the RegulomeDB as this
      database only provides information of few regulatory elements. CONCLUSION: This
      study further supports that some of the noncoding GWAS variants are the true
      associations and not the tag ones. This study also proves the utility and
      importance of the RegulomeDB and other such databases. Although it is an
      extensive database of regulatory elements but has certain limitation due to
      utilization of only few types of regulatory elements and pathways.

PMID- 25585594
TI  - Excess mortality in Type 1 diabetes diagnosed in childhood and adolescence: a
      systematic review of population-based cohorts.
AB  - AIMS: Systematic review of mortality in childhood-/adolescent-diagnosed Type 1
      diabetes and examination of factors explaining the mortality variation between
      studies. METHODS: Relevant studies were identified from systematic searches of
      MEDLINE and EMBASE. Observed and expected numbers of deaths were extracted, and
      standardised mortality ratios (SMRs) and 95 % confidence intervals (CIs) were
      calculated. Negative binomial regression was used to investigate association
      between mortality and study/country characteristics. RESULTS: Thirteen relevant
      publications with mortality data were identified describing 23 independent
      studies. SMRs varied markedly ranging from 0 to 854 (chi (2) = 70.68, df = 21, P
      < 0.0001). Significant associations were observed between SMR and mid-year of
      follow-up [incidence rate ratio (IRR) 0.95, 95 % CI 0.91-0.99 equivalent to a 5 %
      decrease per year], between SMR and infant mortality rate (IRR 1.07, 95 % CI 1.02
      1.12, a 7 % increase for each death per 1,000 live births) and, after omitting an
      outlier, between SMR and health expenditure as a percentage of gross domestic
      product (GDP) (IRR 0.79, 95 % CI 0.68-0.93, a 21 % decrease for each one percent
      increase in GDP). No relationship was detected between SMR and a country's
      childhood diabetes incidence rate or GDP. CONCLUSIONS: Excess mortality in
      childhood-/adolescent-diagnosed Type 1 diabetes is apparent across countries
      worldwide. Excesses were less marked in more recent studies and in countries with
      lower infant mortality and higher health expenditure.

PMID- 25585592
TI  - Systematic review and meta-analysis of randomized clinical trials comparing
      efficacy and safety outcomes of insulin glargine with NPH insulin, premixed
      insulin preparations or with insulin detemir in type 2 diabetes mellitus.
AB  - AIMS: A variety of basal insulin preparations are used to treat patients with
      type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on
      relative efficacy and safety of insulin glargine (IGlar) and other insulins in
      T2DM. METHODS: A systematic review was carried out in major medical databases up
      to December 2012. Relevant studies compared efficacy and safety of IGlar, added
      to oral drugs (OAD) or/and in combination with bolus insulin, with protamine
      insulin (NPH) or premixed insulin (MIX) in the same regimen, as well as with
      insulin detemir (IDet), in T2DM. Target HbA1c level without hypoglycemic events
      was considered the primary endpoint. RESULTS: Twenty eight RCTs involving 12,669
      T2DM patients followed for 12-52 weeks were included in quantitative analysis.
      IGlar + OAD use was associated with higher probability of reaching target HbA1c
      level without hypoglycemia as compared to NPH + OAD (RR = 1.32 [1.09, 1.59]) or
      MIX without OAD (RR = 1.61 [1.22, 2.13]) and similar effect as IDet + OAD (RR =
      1.07 [0.87, 1.33]) and MIX + OAD (RR = 1.09 [0.86, 1.38]). IGlar + OAD
      demonstrated significantly lower risk of symptomatic hypoglycemia as compared to
      NPH + OAD (RR = 0.89 [0.83, 0.96]), MIX + OAD (RR = 0.75 [0.68, 0.83]) and MIX
      without OAD(RR = 0.75 [0.68, 0.83]), but not with IDet + OAD (RR = 0.99 [0.90,
      1.08]). In basal-bolus regimens, IGlar demonstrated similar proportion of T2DM
      patients achieving target HbA1c as compared to NPH (RR = 1.14 [0.91, 1.44]) but
      higher than MIX (RR = 1.26 [1.12, 1.42) or IDet (RR = 1.38 [1.11, 1.72]). The
      risk of severe hypoglycemia was lower in IGlar than in NPH (RR = 0.77 [0.63,
      0.94]), with no differences in comparison with MIX (RR = 0.74 [0.46, 1.20]) and
      IDet (RR = 1.10 [0.54, 2.25]). IGlar + OAD has comparable safety profile to NPH,
      with less frequent adverse events leading to treatment discontinuation than MIX +
      OAD (RR = 0.41 [0.22, 0.76]) and IDet + OAD (RR = 0.40 [0.24, 0.69]). Also severe
      adverse reactions were less common for IGlar + OAD when compared to MIX + OAD (RR
      = 0.71 [0.52; 0.98]). CONCLUSION: For the majority of examined efficacy and
      safety outcomes, IGlar use in T2DM patients was superior or non-inferior to the
      alternative insulin treatment options.

PMID- 25585595
TI  - Patient navigation based on predictive modeling decreases no-show rates in cancer
      care.
AB  - BACKGROUND: Patient adherence to appointments is key to improving outcomes in
      health care. "No-show" appointments contribute to suboptimal resource use.
      Patient navigation and telephone reminders have been shown to improve cancer care
      and adherence, particularly in disadvantaged populations, but may not be cost
      effective if not targeted at the appropriate patients. METHODS: In 5 clinics
      within a large academic cancer center, patients who were considered to be likely
      (the top 20th percentile) to miss a scheduled appointment without contacting the
      clinic ahead of time ("no-shows") were identified using a predictive model and
      then randomized to an intervention versus a usual-care group. The intervention
      group received telephone calls from a bilingual patient navigator 7 days before
      and 1 day before the appointment. RESULTS: Over a 5-month period, of the 40,075
      appointments scheduled, 4425 patient appointments were deemed to be at high risk
      of a "no-show" event. After the patient navigation intervention, the no-show rate
      in the intervention group was 10.2% (167 of 1631), compared with 17.5% in the
      control group (280 of 1603) (P<.001). Reaching a patient or family member was
      associated with a significantly lower no-show rate (5.9% and 3.0%, respectively;
      P<.001 and .006, respectively) compared with leaving a message (14.7%: P = .117)
      or no contact (no-show rate, 21.6%: P = .857). CONCLUSIONS: Telephone navigation
      targeted at those patients predicted to be at high risk of visit nonadherence was
      found to effectively and substantially improve patient adherence to cancer clinic
      appointments. Further studies are needed to determine the long-term impact on
      patient outcomes, but short-term gains in the optimization of resources can be
      recognized immediately.

PMID- 25585596
TI  - The diagnostic value of a new fecal marker, matrix metalloprotease-9, in
      different types of inflammatory bowel diseases.
AB  - BACKGROUND: Only limited data are available regarding the diagnostic accuracy of
      fecal matrix metalloprotease-9 [MMP-9] for inflammatory bowel disease [IBD]. The
      aims of our study were to assess the diagnostic accuracy of fecal MMP-9 in
      patients with active Crohn's disease [CD], ulcerative colitis [UC], and
      pouchitis, and to compare the diagnostic accuracy of fecal MMP-9 and fecal
      calprotectin [CP] in IBD. METHODS: Stool and blood samples were collected in 50
      CD, 54 UC, and 34 ileal pouch-anal anastomosis patients before control
      endoscopies were performed. Biopsies were taken for histologic purposes. The
      activities of CD, UC, and pouchitis were defined with the use of clinical,
      endoscopic, and histologic activity scores. Fecal CP and MMP-9 levels were
      quantified by enzyme-linked immunosorbent assay. RESULTS: Active CD, UC, and
      pouchitis were detected in 38%, 54%, and 29% of the patients, respectively. A
      significant correlation was revealed between fecal CP and the clinical activities
      of CD and UC, and between fecal CP and the endoscopic activity of UC and
      pouchitis. Fecal MMP-9 did not correlate with any of the activity indices of CD;
      however, strong associations were shown between fecal MMP-9 and clinical,
      endoscopic, and histologic activities of both UC and pouchitis. CONCLUSIONS: This
      is the first study assessing the diagnostic accuracy of MMP-9 in different types
      of IBD. Our results showed that fecal MMP-9 has high sensitivity in the detection
      of endoscopically active UC and pouchitis. These non-invasive methods help assess
      intestinal inflammation.

PMID- 25585597
TI  - Melatonin influences somatostatin secretion from human pancreatic delta-cells via
      MT1 and MT2 receptors.
AB  - Melatonin is an effector of the diurnal clock on pancreatic islets. The membrane
      receptor-transmitted inhibitory influence of melatonin on insulin secretion is
      well established and contrasts with the reported stimulation of glucagon release
      from alpha-cells. Virtually, nothing is known concerning the melatonin-mediated
      effects on islet delta-cells. Analysis of a human pancreatic delta-cell model,
      the cell line QGP-1, and the use of a somatostatin-specific radioimmunoassay
      showed that melatonin primarily has an inhibitory effect on somatostatin
      secretion in the physiological concentration range. In the pharmacological range,
      melatonin elicited slightly increased somatostatin release from delta-cells.
      Cyclic adenosine monophosphate (cAMP) is the major second messenger dose
      dependently stimulating somatostatin secretion, in experiments employing the
      membrane-permeable 8-Br-cAMP. 8-Br-cyclic guanosine monophosphate proved to be of
      only minor relevance to somatostatin release. As the inhibitory effect of 1 nm
      melatonin was reversed after incubation of QGP-1 cells with the nonselective
      melatonin receptor antagonist luzindole, but not with the MT2-selective
      antagonist 4-P-PDOT (4-phenyl-2-propionamidotetraline), an involvement of the MT1
      receptor can be assumed. Somatostatin release from the delta-cells at low glucose
      concentrations was significantly inhibited during co-incubation with 1 nm
      melatonin, an effect which was less pronounced at higher glucose levels.
      Transient expression experiments, overexpressing MT1, MT2, or a deletion variant
      as a control, indicated that the MT1 and not the MT2 receptor was the major
      transmitter of the inhibitory melatonin effect. These data point to a significant
      influence of melatonin on pancreatic delta-cells and on somatostatin release. 

PMID- 25585598
TI  - Methylcobalamine is effective in peripheral neuropathies.

PMID- 25585599
TI  - Polyunsaturated fatty acids in relation to incident mobility disability and
      decline in gait speed; the Age, Gene/Environment Susceptibility-Reykjavik Study.
AB  - BACKGROUND/OBJECTIVES: Low intake of long chain polyunsaturated fatty acids
      (PUFAs) are associated with physical disability; however, prospective studies of
      circulating PUFAs are scarce. We examined associations between plasma
      phospholipid n-3 and n-6 PUFAs with risk of incident mobility disability and gait
      speed decline. SUBJECTS/METHODS: Data are from a subgroup of the Age,
      Gene/Environment Susceptibility-Reykjavik Study, a population-based study of risk
      factors for disease and disability in old age. In this subgroup (n = 556, mean
      age 75.1 +/- 5.0 years, 47.5% men), plasma phospholipid PUFAs were assessed at
      baseline using gas chromatography. Mobility disability and usual gait speed were
      assessed at baseline and after 5.2 +/- 0.2 years. Mobility disability was defined
      as the following: having much difficulty, or being unable to walk 500 m or climb
      up 10 steps; decline in gait speed was defined as change ? 0.10 m/s. Logistic
      regression analyses were performed to determine associations between sex-specific
      s.d. increments in PUFAs with risk of incident mobility disability and gait speed
      decline. Odds ratios (95% confidence intervals) adjusted for demographics, follow
      up time, risk factors and serum vitamin D were reported. RESULTS: In women, but
      not men, every s.d. increment increase of total n-3 PUFAs and docosahexaenoic
      acid (DHA) was associated with lower mobility disability risk, odds ratio 0.48
      (0.25; 0.93) and odds ratio 0.45 (0.24; 0.83), respectively. There was no
      association between n-6 PUFAs and the risk of incident mobility disability or
      gait speed decline. CONCLUSIONS: Higher concentrations of n-3 PUFAs and,
      particularly, DHA may protect women from impaired mobility but does not appear to
      have such an effect in men.

PMID- 25585602
TI  - Optic nerve pilomyxoid astrocytoma in a patient with Noonan syndrome.
AB  - Noonan syndrome (NS; MIM 163950) is an autosomal dominant syndrome which is
      clinically diagnosed by the distinct facial features, short stature, cardiac
      anomalies and developmental delay. About 50% of cases are associated with gain of
      function mutations in PTPN11 gene which leads to activation of the RAS/mitogen
      activated protein kinase signaling pathway. This is known to have a role in
      tumorigenesis. Despite this, only limited reports of solid tumors (Fryssira H,
      Leventopoulos G, Psoni S, et al. Tumor development in three patients with Noonan
      syndrome. Eur J Pediatr 2008;167:1025-1031; Schuettpelz LG, McDonald S, Whitesell
      K et al. Pilocytic astrocytoma in a child with Noonan syndrome. Pediatr Blood
      Cancer 2009;53:1147-1149; Sherman CB, Ali-Nazir A, Gonzales-Gomez I, et al.
      Primary mixed glioneuronal tumor of the central nervous system in a patient with
      Noonan syndrome. J Pediatr Hematol Oncol 2009;31:61-64; Sanford RA, Bowman R,
      Tomita T, et al. A 16 year old male with Noonan's syndrome develops progressive
      scoliosis and deteriorating gait. Pediatr Neurosurg 1999;30:47-52) and no prior
      reports of optic gliomas have been described in patients with NS. We present here
      a patient with NS with a PTPN11 mutation and an optic pathway pilomyxoid
      astrocytoma.

PMID- 25585603
TI  - Phase asymmetry of heart rate variability signal.
AB  - Heart rate asymmetry (HRA) is considered as a physiological phenomenon in healthy
      subjects. In this article, we propose a novel HRA index, Slope Index (SI), to
      quantify phase asymmetry of heart rate variability (HRV) system. We assessed the
      performance of proposed index in comparison with conventional (Guzik's Index (GI)
      and Porta's Index (PI)) HRA indices. As illustrative examples, we used two case
      studies: (i) differentiate physiologic RR series from synthetic RR series; and
      (ii) discriminate arrhythmia subjects from Healthy using beat-to-beat heart rate
      time series. The results showed that SI is a superior parameter than GI and PI
      for both case studies with maximum ROC area of 0.84 and 0.82 respectively. In
      contrast, GI and PI had ROC areas {0.78, 0.61} and {0.50, 0.56} in two case
      studies respectively. We also performed surrogate analysis to show that phase
      asymmetry is caused by a physiologic phenomena rather than a random nature of the
      signal. In conclusion, quantification of phase asymmetry of HRV provides
      additional information on HRA, which might have a potential clinical use to
      discriminate pathological HRV in future. 

PMID- 25585601
TI  - The influence of body mass index on the accumulation of advanced glycation end
      products in hemodialysis patients.
AB  - BACKGROUND/OBJECTIVES: The level of skin autofluorescence (AF) at a given moment
      is an independent predictor of mortality in hemodialysis (HD) patients. Skin AF
      is a measure of the accumulation of advanced glycation end products (AGEs). The
      aim of the study was to estimate the influence of nutrition on the 1-year
      increase of skin AF (DeltaAF) in HD patients. SUBJECTS/METHODS: A total of 156 HD
      patients were enrolled in this study. Skin AF, body mass index (BMI), superoxide
      dismutase, myeloperoxidase, C-reactive protein, inter-cellular adhesion molecule
      1, von Willebrand factor and heart-type fatty acid-binding protein were measured
      four times at intervals of approximately half a year. Data from the monthly
      routine blood analysis were also used. Daily calorie, protein and AGE intakes
      were assessed from food recordings over a period of 1 week. RESULTS: A J-shaped
      relation was found between baseline BMI and DeltaAF (P=0.01). The lowest point of
      the J-shaped curve is found for BMI=24.3 kg/m(2). In the univariate analysis of
      the contributors to the 1-year DeltaAF, we found that beside BMI=24.3 kg/m(2),
      AGE and calorie intakes, as well as myeloperoxidase and HD vintage, had a P
      <0.10. The sole independent predictor of the 1-year DeltaAF was BMI=24.3 kg/m(2)
      (P=0.01). CONCLUSIONS: It appears that calorie, protein and AGE intakes hardly
      influence the 1-year DeltaAF in HD patients. BMI of HD patients of around 24
      kg/m(2) resulted in a lower 1-year DeltaAF.

PMID- 25585600
TI  - Fruit and vegetable intake and mortality from cardiovascular disease in Japan: a
      24-year follow-up of the NIPPON DATA80 Study.
AB  - BACKGROUND/OBJECTIVES: There have been few studies on the association of fruit
      and vegetable (FV) intake with cardiovascular disease (CVD) risk in Asian
      populations where both dietary habits and disease structure are different from
      western countries. No study in Asia has found its significant association with
      stroke. We examined associations of FV intake with mortality risk from total CVD,
      stroke and coronary heart diseases (CHDs) in a representative Japanese sample.
      METHODS: A total of 9112 participants aged from 24-year follow-up data in the
      NIPPON DATA80, of which baseline data were obtained in the National Nutrition
      Survey Japan in 1980, were studied. Dietary data were obtained from 3-day
      weighing dietary records. Participants were divided into sex-specific quartiles
      of energy adjusted intake of FV. Multivariate-adjusted hazard ratios (HRs) were
      calculated between strata of the total of FV intake, fruit intake and vegetable
      intake. The adjustment included age, sex, smoking, drinking habit and energy
      adjusted intakes of sodium and some other food groups. RESULTS: Participants with
      higher FV intake were older, ate more fish, milk and dairy products and soybeans
      and legumes and ate less meat. Multivariate-adjusted HR (95% confidence interval;
      P; P for trend) for the highest versus the lowest quartile of the total of FV
      intake was 0.74 (0.61-0.91; 0.004; 0.003) for total CVD, 0.80 (0.59-1.09; 0.105;
      0.036) for stroke and 0.57 (0.37-0.87; 0.010; 0.109) for CHD. CONCLUSIONS: The
      results showed that higher total intake of FVs was significantly associated with
      reduced risk of CVD mortality in Japan.

PMID- 25585604
TI  - Prediction of small-for-gestational-age neonates: screening by uterine artery
      Doppler and mean arterial pressure at 30-34 weeks.
AB  - OBJECTIVE: To investigate the potential value of uterine artery (UtA) pulsatility
      index (PI) and mean arterial pressure (MAP) at 30-34 weeks' gestation in the
      prediction of small-for-gestational-age (SGA) neonates, in the absence of pre
      eclampsia (PE). METHODS: This was a screening study in singleton pregnancies at
      30-34 weeks' gestation, including 1727 that delivered SGA neonates with a birth
      weight < 5(th) percentile and 29 122 that were unaffected by SGA, PE or
      gestational hypertension (normal group). Multivariable logistic regression
      analysis was used to determine if measuring the UtA-PI and MAP improved the
      prediction of SGA neonates provided by screening with maternal characteristics
      and medical history (maternal factors), and estimated fetal weight (EFW)
      calculated from fetal head circumference, abdominal circumference and femur
      length. RESULTS: Combined screening by maternal factors and EFW Z-scores
      predicted 79%, 87% and 92% of SGA neonates delivering < 5 weeks following
      assessment, with a birth weight < 10(th) , < 5(th) and < 3(rd) percentiles,
      respectively, at a false-positive rate of 10%. The addition of UtA-PI and MAP
      improved the respective detection rates to 83%, 91% and 93%. Screening by
      maternal factors and EFW Z-scores predicted 53%, 58% and 61% of SGA delivering >=
      5 weeks following assessment and these rates increased to 53%, 60% and 63% with
      the addition of UtA-PI and MAP. CONCLUSION: Combined testing by maternal factors,
      fetal biometry, UtA-PI and MAP at 30-34 weeks' gestation could identify a high
      proportion of pregnancies that deliver SGA neonates.

PMID- 25585605
TI  - In vivo anthelmintic activity of Carex baccans and its active principle
      resveratrol against Hymenolepis diminuta.
AB  - Anthelmintic resistance against most of the commercial drugs is a great threat to
      humans as well as the veterinary live stocks. Hence, new treatment strategies to
      control helminth infections are essential at this hour. Carex baccans Nees has
      been traditionally used by Jaintia tribes in Northeast India to get rid of
      intestinal worm infections. Therefore, the present study was conducted to
      evaluate in vivo cestocidal activity of root tuber extract of C. baccans and its
      active component resveratrol against the zoonotic cestode Hymenolepis diminuta in
      the experimental model rat. The cestocidal activity was determined by monitoring
      the eggs per gram (EPG) counts in faeces of different treated groups. The result
      showed that the highest dose of the plant extract (50 mg/kg) and resveratrol
      (4.564 mg/kg body weight) has significant anthelmintic efficacy against H.
      diminuta. Crude extract of the plant as well as resveratrol reduced EPG count
      (56.012 and 46.049 %) and also resulted in decreased worm burden by 44.287 and
      31.034 %, respectively. The efficacy of the crude extract and resveratrol can be
      compared to the reference drug praziquantel. The results exhibits considerable
      cestocidal potential of root tuber crude extract of C. baccans and resveratrol
      and justify its folklore use. 

PMID- 25585606
TI  - Myxozoan infections of the three Indian major carps in fish ponds around Meerut,
      UP, India, with descriptions of three new species, Myxobolus basuhaldari sp. n.,
      M. kalavatiae sp. n. and M. meerutensis sp. n., and the redescription of M.
      catlae and M. bhadrensis.
AB  - New myxosporean species are described from Indian fishes cultured in pond farms
      of Meerut, Uttar Pradesh (UP) state. Based upon plasmodia found in the Indian
      major carps (Catla catla, Cirrhinus cirrhosus, Labeo rohita and their hybrids),
      three new Myxobolus spp., Myxobolus basuhaldari sp. n., Myxobolus kalavatiae sp.
      n. and Myxobolus meerutensis sp. n., are described, and two species, Myxobolus
      catlae and Myxobolus bhadrensis, are redescribed. Plasmodia of M. basuhaldari sp.
      n., M. kalavatiae sp. n., M. meerutensis sp. n. and M. catlae developed in small
      cysts in the gill lamellae, while plasmodia and scattered spores of M. bhadrensis
      were found in the muscles and kidney, respectively. Plasmodia and spores found in
      these fishes differed from each other with respect to their morphology, tissue
      tropism and 18S ribosomal DNA (18S rDNA) sequence. No major pathological changes
      were found, but severe infections were observed. 

PMID- 25585608
TI  - Extended lateral pelvic sidewall excision (ELSiE): an approach to optimize
      complete resection rates in locally advanced or recurrent anorectal cancer
      involving the pelvic sidewall.

PMID- 25585607
TI  - Low toxicity and long circulation time of polyampholyte-coated magnetic
      nanoparticles for blood pool contrast agents.
AB  - Polyampholyte-coated (poly(acrylic acid) (PAA)-co-3-(diethylamino)-propylamine
      (DEAPA)) magnetite nanoparticles (PAMNPs) have been prepared as contrasting agent
      used in magnetic resonance imaging (MRI). Excellent biocompatibility is required
      for contrasting agents used in high-resolution magnetic resonance angiography. To
      evaluate the biocompatibility of PAMNPs, some experiments have been conducted.
      The hemolysis, plasma recalcification, dynamic blood clotting, prothrombin time,
      inflammatory cytokine release and complement system activation assays were
      carried out to investigate the hemocompatibility. To evaluate the toxicity to
      vessel, MTT test and vascular irritation tests were conducted. Tissue toxicity
      test was also performed to investigate the biocompability in vivo. We also looked
      into the biodistribution. The results showed that PAMNPs at the working
      concentration (0.138 mM) present similar hemocompatibility with negative control,
      thus have no significant effect to vessels. PAMNPs were mainly distributed in the
      liver and the blood. The circulation time in blood was considerably long, with
      the half-time of 3.77 h in plasma. This property is advantageous for PAMNPs' use
      in angiography. PAMNPs could be metabolized rapidly in mice and were not observed
      to cause any toxic or adverse effect. In short, these results suggest that the
      PAMNPs have great potential to serve as safe contrast agents in magnetic
      resonance imaging (MRI).

PMID- 25585609
TI  - Profiling of cis-diol-containing nucleosides and ribosylated metabolites by
      boronate-affinity organic-silica hybrid monolithic capillary liquid
      chromatography/mass spectrometry.
AB  - RNA contains a large number of modified nucleosides. In the metabolic re-exchange
      of RNA, modified nucleosides cannot be recycled and are thus excreted from cells
      into biological fluids. Determination of endogenous modified nucleosides in
      biological fluids may serve as non-invasive cancers diagnostic methods. Here we
      prepared boronate-affinity organic-silica hybrid capillary monolithic column
      (BOHCMC) that exhibited excellent selectivity toward the cis-diol-containing
      compounds. We then used the prepared BOHCMC as the on-line solid-phase
      microextraction (SPME) column and developed an on-line SPME-LC-MS/MS method to
      comprehensively profile cis-diol-containing nucleosides and ribosylated
      metabolites in human urine. Forty-five cis-diol-containing nucleosides and
      ribosylated metabolites were successfully identified in human urine. And five
      ribose conjugates, for the first time, were identified existence in human urine
      in the current study. Furthermore, the relative quantification suggested 4 cis
      diol-containing compounds (5'-deoxy-5'-methylthioadensine, N(4)-acetylcytidine, 1
      ribosyl-N-propionylhistamine and N(2),N(2),7-trimethylguanosine) increased more
      than 1.5 folds in all the 3 types of examined cancers (lung cancer, colorectal
      cancer, and nasopharyngeal cancer) compared to healthy controls. The on-line SPME
      LC-MS/MS method demonstrates a promising method for the comprehensive profiling
      of cis-diol-containing ribose conjugates in human urines, which provides an
      efficient strategy for the identification and discovery of biomarkers and may be
      used for the screening of cancers. 

PMID- 25585610
TI  - The neuroprotection of repetitive transcranial magnetic stimulation pre-treatment
      in vascular dementia rats.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique
      that could interfere cortical excitability though brief electric currents induced
      by alternating magnetic fields from the inductive coil. Currently, it has been
      applied in many fields of basic and clinical neuro-research. The aims of the
      present study are to investigate the effect of rTMS pre-treatment on cognitive
      function in vascular dementia (VaD) rats and further explore the molecular
      mechanism of rTMS neuroprotection on VaD. We found that rTMS pre-treated VaD rats
      showed significantly better memory and learning abilities in Morris water maze
      test compared to the untreated group. Moreover, the mRNA and protein expression
      levels of BDNF, TrkB, and SYN were significantly higher in the rTMS pre-treated
      group, indicating that rTMS pre-treatment has neuroprotective effect for VaD,
      which may have resulted from the increased level of BDNF, TrkB, and SYN in the
      hippocampal CA1 area. 

PMID- 25585612
TI  - One thousand single anastomosis (omega loop) gastric bypasses to treat morbid
      obesity in a 7-year period: outcomes show few complications and good efficacy.
AB  - BACKGROUND: A short-term randomized controlled trial shows that the one
      anastomosis gastric bypass (OAGB) is a safe and effective alternative to the Roux
      en-Y gastric bypass (RYGB). OBJECTIVE: The aim of this study is to evaluate the
      OAGB at our University Hospital between 2006 and 2013. PATIENTS: One thousand
      patients have undergone an OAGB. Data were collected on all consecutive patients.
      The mean follow-up period was 31 months (SD, 26.3; range, 12-82.9), and complete
      follow-up was available in 126 of 175 patients (72 %) at 5 years after surgery.
      RESULTS: Mortality rate was 0.2 %. Overall morbidity was 5.5 %; 34 required
      reoperations: i.e., 6 leaks, 5 obstructions, 5 incisional hernias, 7 biliary
      refluxes, 2 perforated ulcers, 2 bleeds, 2 abscesses, and 1 anastomotic
      stricture. Four patients were reoperated for weight regain. Overall rate of
      marginal ulcers was 2 % (n = 20), all in heavy smokers. Conversion from an OAGB
      to a RYGB was required in nine cases (0.9 %): seven for intractable biliary
      reflux, two for a marginal ulcer. At 5 years, percent excess body mass index loss
      was 71.6 +/- 27 %. One hundred patients with type-2 diabetes, with a mean
      preoperative HbA1C of 7.7 +/- 1.9 %, were followed for >2 years; the total
      resolution rate was 85.7 %. CONCLUSION: This study confirms that the OAGB is an
      effective procedure for morbid obesity with comparable outcomes to RYGB; in
      addition, it seems to be safer with lower morbidity. Its technical simplicity
      represents a real advantage and makes it an option that should be considered by
      all bariatric surgeons.

PMID- 25585611
TI  - Progress on Nme (NDP kinase/Nm23/Awd) gene family-related functions derived from
      animal model systems: studies on development, cardiovascular disease, and cancer
      metastasis exemplified.

PMID- 25585613
TI  - Changes in Hematology and Calcium Metabolism After Gastric Bypass Surgery--a 2
      Year Follow-Up Study.
AB  - BACKGROUND: Concerns regarding nutritional deficiencies have recently emerged
      after Roux-en-Y gastric bypass (RYGB). METHODS: A total of 835 subjects underwent
      RYGB, age 43.3 years, body mass index (BMI) 47.2 kg/m(2). Hematological and
      calcium metabolic variables were measured before, 6, 12, and 24 months after
      surgery. Daily supplement of 800 mg calcium, 800 U vitamin D, a multivitamin, and
      a vitamin B12 injection (1 mg) every third month was recommended. In subjects
      with low ferritin and decreasing hemoglobin levels, oral, or intravenous iron was
      administered. RESULTS: Hemoglobin concentration decreased from before surgery to
      month 24 for both men (9.3 +/- 0.05 vs. 8.3 +/- 0.08 mmol/L, p < 0.001) and women
      (8.4 +/- 0.03 vs. 7.7 +/- 0.06 mmol/L, p < 0.001). At 24 months, anemia was
      present in 25.8 % of women and 22.1 % of men. Predictors of anemia in both sexes
      were baseline hemoglobin (p < 0.001), excessive weight loss in men, and younger
      age in women (p < 0.001). Plasma ferritin levels decreased in both sexes (p <
      0.01), whereas concentrations of folic acid and vitamin B12 increased from before
      surgery to 24 months after surgery (p < 0.001). Vitamin D increased from baseline
      to month 24 in both sexes (p < 0.01). In women, PTH increased from baseline to
      month 24 (p < 0.05) with no changes in calcium or magnesium. CONCLUSIONS:
      Supplementation of calcium and vitamin D was sufficient. Iron substitution did
      not prevent anemia, which especially affected premenopausal women. More attention
      should be given to iron substitution after RYGB.

PMID- 25585614
TI  - Results of remote follow-up and monitoring in young patients with cardiac
      implantable electronic devices.
AB  - BACKGROUND: Remote monitoring is increasingly used in the follow-up of patients
      with cardiac implantable electronic devices. Data on paediatric populations are
      still lacking. The aim of our study was to follow-up young patients both in
      hospital and remotely to enhance device surveillance. METHODS: This is an
      observational registry collecting data on consecutive patients followed-up with
      the CareLink system. Inclusion criteria were a Medtronic device implanted and
      patient's willingness to receive CareLink. Patients were stratified according to
      age and presence of congenital/structural heart defects (CHD). RESULTS: A total
      of 221 patients with a device - 200 pacemakers, 19 implantable cardioverter
      defibrillators, and two loop recorders--were enrolled (median age of 17 years,
      range 1-40); 58% of patients were younger than 18 years of age and 73% had CHD.
      During a follow-up of 12 months (range 4-18), 1361 transmissions (8.9%
      unscheduled) were reviewed by technicians. Time for review was 6 +/- 2 minutes
      (mean +/- standard deviation). Missed transmissions were 10.1%. Events were
      documented in 45% of transmissions, with 2.7% yellow alerts and 0.6% red alerts
      sent by wireless devices. No significant differences were found in transmission
      results according to age or presence of CHD. Physicians reviewed 6.3% of
      transmissions, 29 patients were contacted by phone, and 12 patients underwent
      unscheduled in-hospital visits. The event recognition with remote monitoring
      occurred 76 days (range 16-150) earlier than the next scheduled in-office follow
      up. CONCLUSIONS: Remote follow-up/monitoring with the CareLink system is useful
      to enhance device surveillance in young patients. The majority of events were not
      clinically relevant, and the remaining led to timely management of problems.

PMID- 25585615
TI  - Improving the bioactivity of rHirudin with boronophenylalanine site-specific
      modification.
AB  - To improve the bioactivity of recombinant (r)Hirudin, the orthogonal pair
      MjBTyrRS/tRNATyr cua (made up of the boronophenylalanine, tRNA and tRNA
      synthetase), was selected to incorporate boronophenylalanine site-specifically
      into rHirudin at the 63 sites in an Escherichia coli system in response to the
      TAG codon. Following fusion with the gIII signal peptide and a hexahistidine tag,
      the modified protein was secreted into Luria-Bertani culture medium and purified
      by nickel-nitrilotriacetic acid affinity chromatography following a gel
      filtration column. In a 200 ml flask, the yield of boronophenylalanine-modified
      hirudin was 10 mg l-1 and that of rHirudin was 19 mg l-1. The authenticity of the
      purified proteins was verified using matrix-assisted laser desorption ionization
      time of flight mass spectroscopy and antithrombin activity assays. The results
      revealed that the antithrombin activity of the boronophenylalanine-modified
      hirudin to human thrombin was more enhanced than that of rHirudin. The modified
      hirudin demonstrated stronger proliferation inhibiting ability on fibroblast L929
      cells compared with that of rHirudin.

PMID- 25585616
TI  - Examination of unplanned 30-day readmissions to a comprehensive cancer hospital.
AB  - PURPOSE: The Centers for Medicare and Medicaid Services (CMS), under the
      Hospitals Readmissions Reductions Program, may withhold regular reimbursements
      for excessive 30-day readmissions for select diagnoses. Such penalties imply that
      some readmissions reflect poor clinical decision making or care during the
      initial hospitalization. We examined factors related to potentially preventable
      readmissions in CMS patients at a tertiary cancer hospital. METHODS: The medical
      records of all CMS patients with unplanned readmissions within 30 days of index
      admission were reviewed over 6 months (October 15, 2011-April 15, 2012). Each
      readmission was classified as not preventable or potentially preventable. Factors
      associated with potentially preventable readmissions were sought. RESULTS: Of
      2,531 inpatient admissions in CMS patients over 6 months, 185 patients
      experienced at least one readmission for 282 total readmissions (11%). Median
      time to readmission was 9 days (range, 0 to 30 days). The most common causes for
      first readmission were new diagnoses not present at first admission (n = 43,
      23%), new or worsening symptoms due to cancer progression (n = 40, 21%) and
      complications of procedures (n = 25, 13%). There were 38 (21%) initial
      readmissions classified as potentially preventable. Use of total parenteral
      nutrition at the time of discharge was associated with potentially preventable
      readmission (P = .028). CONCLUSION: Most unplanned readmissions to a tertiary
      cancer hospital are related to progression of disease, new diagnoses, and
      procedure complications. Minimizing readmissions in complex cancer patients is
      challenging. Larger multi-institutional datasets are needed to determine a
      reasonable standard for expected readmission rates.

PMID- 25585617
TI  - Emergency room visits and hospital admission rates after curative chemotherapy
      for breast cancer.
AB  - PURPOSE: Curative chemotherapy for breast cancer is associated with significant
      toxicities including emergency room (ER) visits and hospital admissions (HAs),
      events that are underreported in clinical trials. This study examined the reasons
      for, and factors associated with, ER visits and HA after curative chemotherapy
      for breast cancer in a tertiary Ontario hospital. PATIENTS AND METHODS: A
      retrospective study of all patients who completed at least one cycle of curative
      chemotherapy for breast cancer in 2011 and 2012 was conducted. We recorded ER
      visits and HAs within 30 days of any chemotherapy. We collected demographics,
      comorbidities, surgical data, tumor characteristics, chemotherapy type and
      cycles, and use of granulocyte colony-stimulating factors (G-CSF). RESULTS: A
      total of 149 patients underwent curative chemotherapy. Mean age was 58.6 years.
      Adjuvant chemotherapy was received by 85% of patients and G-CSF by 88.6%. At
      least one ER visit occurred in 53% of patients, and 13% required HA. The most
      common causes of ER visits were fever without neutropenia (23.3%), pain (12.8%),
      and febrile neutropenia (9%). Stage of breast cancer was the only factor
      statistically significantly associated with ER visits (P = .045); tumor size (P =
      .019), adjuvant chemotherapy (P = .045), and lower number of chemotherapy cycles
      (P = .005) were significantly associated with HA. CONCLUSION: Future research
      should focus on identifying the patient, provider, and health system factors
      associated with ER visits and HAs after chemotherapy for breast cancer, to
      minimize them and lessen the burden on the health care system.

PMID- 25585618
TI  - Detection models for freehand SPECT reconstruction.
AB  - Nuclear imaging modalities are commonly used tools in today's diagnostics and
      therapy planning. However for interventional use they suffer from drawbacks which
      limit their application. Freehand SPECT was developed to provide 3D functional
      imaging during interventions. It combines a nuclear detector with an optical
      tracking system to obtain its position and orientation in space and synchronizes
      this with the detector readings. This information can be used to compute a 3D
      tomographic reconstruction of an activity distribution of a nuclear tracer. As
      there is no fixed geometry, the system matrix has to be computed on the fly. This
      is done with models of the detection process for completely arbitrary freehand
      acquisitions. The accuracy of the reconstructions is highly dependent on the used
      models of the detection process. Different models of the detection process were
      developed and evaluated in this work, in particular two analytical models as well
      as lookup tables generated from either real measurements or Monte Carlo
      simulations. We showed that it is possible to perform acceptable reconstructions
      with a simple but efficient analytical model. The use of lookup tables to
      generate the system matrix in Freehand SPECT is a fast solution with good
      accuracy.

PMID- 25585619
TI  - Genome-wide analysis of PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE (PDAT) genes
      in plants reveals the eudicot-wide PDAT gene expansion and altered selective
      pressures acting on the core eudicot PDAT paralogs.
AB  - PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE (PDAT) is an enzyme that catalyzes
      the transfer of a fatty acyl moiety from the sn-2 position of a phospholipid to
      the sn-3-position of sn-1,2-diacylglyerol, thus forming triacylglycerol and a
      lysophospholipid. Although the importance of PDAT in triacylglycerol biosynthesis
      has been illustrated in some previous studies, the evolutionary relationship of
      plant PDATs has not been studied in detail. In this study, we investigated the
      evolutionary relationship of the PDAT gene family across the green plants using a
      comparative phylogenetic framework. We found that the PDAT candidate genes are
      present in all examined green plants, including algae, lowland plants (a moss and
      a lycophyte), monocots, and eudicots. Phylogenetic analysis revealed the
      evolutionary division of the PDAT gene family into seven major clades. The
      separation is supported by the conservation and variation in the gene structure,
      protein properties, motif patterns, and/or selection constraints. We further
      demonstrated that there is a eudicot-wide PDAT gene expansion, which appears to
      have been mainly caused by the eudicot-shared ancient gene duplication and
      subsequent species-specific segmental duplications. In addition, selection
      pressure analyses showed that different selection constraints have acted on three
      core eudicot clades, which might enable paleoduplicated PDAT paralogs to either
      become nonfunctionalized or develop divergent expression patterns during
      evolution. Overall, our study provides important insights into the evolution of
      the plant PDAT gene family and explores the evolutionary mechanism underlying the
      functional diversification among the core eudicot PDAT paralogs.

PMID- 25585620
TI  - Assessing gene-environment interactions for common and rare variants with binary
      traits using gene-trait similarity regression.
AB  - Accounting for gene-environment (G*E) interactions in complex trait association
      studies can facilitate our understanding of genetic heterogeneity under different
      environmental exposures, improve the ability to discover susceptible genes that
      exhibit little marginal effect, provide insight into the biological mechanisms of
      complex diseases, help to identify high-risk subgroups in the population, and
      uncover hidden heritability. However, significant G*E interactions can be
      difficult to find. The sample sizes required for sufficient power to detect
      association are much larger than those needed for genetic main effects, and
      interactions are sensitive to misspecification of the main-effects model. These
      issues are exacerbated when working with binary phenotypes and rare variants,
      which bear less information on association. In this work, we present a similarity
      based regression method for evaluating G*E interactions for rare variants with
      binary traits. The proposed model aggregates the genetic and G*E information
      across markers, using genetic similarity, thus increasing the ability to detect
      G*E signals. The model has a random effects interpretation, which leads to
      robustness against main-effect misspecifications when evaluating G*E
      interactions. We construct score tests to examine G*E interactions and a
      computationally efficient EM algorithm to estimate the nuisance variance
      components. Using simulations and data applications, we show that the proposed
      method is a flexible and powerful tool to study the G*E effect in common or rare
      variant studies with binary traits. 

PMID- 25585621
TI  - Exploring the association between interleukin-1beta and its interacting proteins
      in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an age-associated progressive neurodegenerative
      disorder which is of clinical concern. The association between the nervous and
      immune system is defined as an neuroimmunological theory that supports a model of
      pathology or treatment for AD. Interleukin (IL)-1beta has a pro-inflammatory
      function in AD; however, the mechanism of its dysregulation in AD remains
      unknown. It is therefore of significance to understand the molecular mechanisms
      of IL-1beta and how it may regulate AD. Proteins, which have been previously
      reported to be associated with IL-1beta in AD, have been used in the present
      study as nodes to illustrate a net of protein interaction in Cytoscape. The Kyoto
      Encyclopedia of Genes and Genomes was used to further analyze the association of
      these proteins with the pathology of AD. The present study identified and
      subsequently compared two AD and six IL-1beta pathways with the network produced
      in Cytoscape. The present study identified important mechanisms in the pathology
      of AD and constructed two novel networks using Cytoscape.

PMID- 25585622
TI  - Pseudogout at the knee joint will frequently occur after hip fracture and lead to
      the knee pain in the early postoperative period.
AB  - BACKGROUND: Symptomatic knee joint effusion is frequently observed after hip
      fracture, which may lead to postoperative knee pain during rehabilitation after
      hip fracture surgery. However, unfortunately, very little has been reported on
      this phenomenon in the literature. The purpose of the current study was to
      investigate the relationship between symptomatic knee effusion and postoperative
      knee pain and to clarify the reason of the effusion accompanied by hip fracture.
      METHODS: A total of 100 patients over 65 years of age with an acute hip fracture
      after fall were prospectively followed up. Knee effusion was assessed on
      admission and at the operating room before the surgery. If knee effusion was
      observed at the time of the surgery, synovial fluid was collected into syringes
      to investigate the cause of the effusion using a compensated polarized light
      microscope. Furthermore, for each patient, we evaluated age, sex, radiographic
      knee osteoarthritis (OA), type of the fracture, laterality, severity of the
      fracture, and postoperative knee pain during rehabilitation. These factors were
      compared between patients with and without knee effusion at the time of the
      surgery. As a statistical analysis, we used Mann-Whitney U-test for patients' age
      and categorical variables were analyzed by chi-square test or Fisher's exact
      test. RESULTS: A total of 30 patients presented symptomatic knee effusion at the
      time of the surgery. In patients with knee effusion, numbers of intertrochanteric
      fracture, radiographic knee OA, and postoperative knee pain were significantly
      large compared to those without effusion. In terms of synovial fluid analysis,
      calcium pyrophosphate dihydrate crystals were observed in 80% of patients with
      knee effusion. CONCLUSION: From our study, approximately 63% of patients with
      knee effusion at the time of the surgery had postoperative knee pain. In
      addition, this effusion was basically related to pseudogout.

PMID- 25585623
TI  - S100P, a calcium-binding protein, is preferentially associated with the growth of
      polypoid tumors in colorectal cancer.
AB  - Colorectal cancer (CRC) is a genetically heterogeneous disease with distinct
      morphological patterns. It has been shown that polypoid and ulcerative CRC
      displays different genetic alterations. In the present study, we aimed to
      investigate genes with differential expression patterns between ulcerative and
      polypoid CRC. cDNA microarray analysis was performed to compare the gene
      expression profiles in samples of ulcerative and polypoid CRC with paired normal
      mucosa samples. Potential candidate genes were further validated using reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR), western blot
      analysis and immunohistochemistry. The epigenetic regulation of gene expression
      was investigated using methylation-specific PCR (MSP). cDNA microarray analysis
      identified 11 upregulated and 14 downregulated genes which were differentially
      expressed in samples from both tumor types compared to the matched normal mucosa
      samples. Among these, S100P was the only upregulated gene preferentially
      associated with polypoid CRC (P=0.032). The samples of polypoid CRC displayed
      significantly higher S100P protein and mRNA expression levels than the samples of
      ulcerative CRC (P<0.05, respectively). Using semi-quantitative
      immunohistochemical analyses, S100P overexpression was found to be preferentially
      associated with polypoid CRC (24/30 vs. 14/40, P<0.001). The relative methylation
      level determined by MSP did not differ significantly between the samples of
      polypoid and ulcerative CRC (43.36 vs. 49.10%, P=0.168), indicating that promoter
      hypomethylation was not directly related to the upregulation of S100P mRNA. Our
      results demonstrate that the upregulation of S100P mRNA and protein expression is
      a predominant characteristic in polypoid CRC, whereas ulcerative CRC presents
      with a wide range of expression levels, indicating that S100P overexpression is
      not a key determinant in conferring invasion properties. The clinicopathological
      significance of S100P in CRC requires further investigation in well-controlled
      studies.

PMID- 25585624
TI  - Role of the monocyte chemoattractant protein-1/C-C chemokine receptor 2 signaling
      pathway in transient receptor potential vanilloid type 1 ablation-induced renal
      injury in salt-sensitive hypertension.
AB  - Our recent studies indicate that the transient receptor potential vanilloid type
      1 (TRPV1) channel may act as a potential regulator of monocyte/macrophage
      recruitment to reduce renal injury in salt-sensitive hypertension. This study
      tests the hypothesis that deletion of TRPV1 exaggerates salt-sensitive
      hypertension-induced renal injury due to enhanced inflammatory responses via
      monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2)
      dependent pathways. Wild type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice were
      subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment
      for four weeks with or without the selective CCR2 antagonist, RS504393. DOCA-salt
      treatment increased systolic blood pressure (SBP) to the same degree in both
      strains, but increased urinary excretion of albumin and 8-isoprostane and
      decreased creatinine clearance with greater magnitude in TRPV1(-/-) mice compared
      to WT mice. DOCA-salt treatment also caused renal glomerulosclerosis,
      tubulointerstitial injury, collagen deposition, monocyte/macrophage infiltration,
      proinflammatory cytokine and chemokine production, and NF-kappaB activation in
      greater degree in TRPV1(-/-) mice compared to WT mice. Blockade of the CCR2 with
      RS504393 (4 mg/kg/day) had no effect on SBP in DOCA-salt-treated WT or TRPV1(-/-)
      mice compared to their respective controls. However, treatment with RS504393
      ameliorated renal dysfunction and morphological damage, and prevented the
      increase in monocyte/macrophage infiltration, cytokine/chemokine production, and
      NF-kappaB activity in both DOCA-salt hypertensive strains with a greater effect
      in DOCA-salt-treated TRPV1(-/-) mice compared to DOCA-salt-treated WT mice. No
      differences in CCR2 protein expression in kidney were found between DOCA-salt
      treated WT and TRPV1(-/-) mice with or without RS504393 treatment. Our studies
      for the first time indicate that deletion of TRPV1 aggravated renal injury in
      salt-sensitive hypertension via enhancing MCP-1/CCR2 signaling-dependent
      inflammatory responses. 

PMID- 25585625
TI  - Deficiency of G-protein coupled receptor 40, a lipid-activated receptor,
      heightens in vitro- and in vivo-induced murine osteoarthritis.
AB  - Osteoarthritis (OA) is an age-related degenerative joint disease. To date, its
      management is focused on symptoms (pain and inflammation). Studies suggest that
      fatty acids can reduce the expression of inflammatory and catalytic mediators,
      and improve in vivo joint function. Free fatty acid receptors (FFARs) such as G
      protein coupled receptor 40 (GPR40) are proposed as attractive therapeutic
      targets to counteract inflammation and cartilage degradation observed in OA. This
      study aims to elucidate the involvement of GPR40 in OA. In this study, we used an
      in vitro model of OA, and surgically induced OA by ligament transection and
      partial meniscectomy in wild-type and GPR40 deficient mice. OA phenotype was
      investigated in vivo by histology and genes expression. We demonstrate that IL
      1beta-treated GPR40(-/-) chondrocytes secret more inflammatory mediators (nitric
      oxide, interleukin-6, prostaglandin E2) and active catabolic enzymes
      (metalloproteinase-2, -9 [MMP-2, MMP-9]), and show decreased anabolism
      (glycoaminoglycan) compared to GPR40(+/+) cells. In accordance with these
      results, we show that GPR40(-/-) mice exhibit an aggravated OA-induced phenotype
      characterized by higher tidemark exposure, frequency of osteophyte formation and
      subchondral bone sclerosis. Altogether our results demonstrate that GPR40
      deficiency leads to an extended OA phenotype, providing evidence that increasing
      GPR40 activity, by natural or synthetic ligands, could be a new strategy in the
      management of OA. 

PMID- 25585627
TI  - AA amyloidosis treated with tocilizumab: case series and updated literature
      review.
AB  - BACKGROUND: In published case reports, tocilizumab (TCZ) has shown good efficacy
      for AA amyloidosis in almost all patients. We investigated the efficacy and
      safety of TCZ in AA amyloidosis in a multicentre study of unselected cases.
      METHODS: We e-mailed rheumatology and internal medicine departments in France,
      Switzerland and North Africa by using the Club Rhumatismes Inflammation (CRI)
      network and the French TCZ registry, Registry RoAcTEmra (REGATE), to gather data
      on consecutive patients with histologically proven AA amyloidosis who had
      received at least one TCZ infusion. Efficacy was defined as a sustained decrease
      in proteinuria level and/or stable or improved glomerular filtration rate (GFR)
      and by TCZ maintenance. RESULTS: We collected 12 cases of AA amyloidosis treated
      with TCZ as monotherapy (mean age of patients 63 +/- 16.2 years, amyloidosis
      duration 20.6 +/- 31.3 months): eight patients had rheumatoid arthritis (RA), six
      with previous failure of anti-tumor necrosis factor alpha (anti-TNF-alpha)
      therapy. In total, 11 patients had renal involvement, with two already on
      hemodialysis (not included in the renal efficacy assessment). For the nine other
      patients, baseline GFR and proteinuria level were 53.6 +/- 32.8 mL/min and 5 +/-
      3.3 g/24 h, respectively. The mean follow-up was 13.1 +/- 11 months. TCZ was
      effective for six of the eight RA patients (87.5%) according to European League
      Against Rheumatism response criteria (four good and two moderate responders). As
      expected, C-reactive protein (CRP) level decreased with treatment for 11
      patients. Renal amyloidosis (n = 9) progressed in three patients and was
      stabilized in three. Overall, three patients showed improvement, with sustained
      decrease in proteinuria level (42%, 82% and 96%). Baseline CRP level was higher
      in subsequent responders to TCZ than other patients (p = 0.02). Among the six RA
      patients with previous anti-TNF-alpha therapy, amyloidosis was ameliorated in one
      and stabilized in three. Three serious adverse events occurred (two
      diverticulitis and one major calciphylaxia due to renal failure). Finally, 7 of
      12 (58%) patients continued TCZ. CONCLUSIONS: The efficacy of TCZ for AA
      amyloidosis varies depending on the inflammatory status at treatment onset.
      Discrepancies between our study of unselected consecutive patients and reported
      cases may be due to publication bias. These results support further prospective
      trials of TCZ for AA amyloidosis.

PMID- 25585626
TI  - Vaspin promotes 3T3-L1 preadipocyte differentiation.
AB  - Vaspin, a novel adipocyte factor secreted from visceral adipose tissues, is
      associated with obesity and insulin resistance and can regulate glucose and lipid
      metabolism, increase insulin sensitivity, and suppress inflammation; however, the
      underlying mechanisms remain unknown. Proliferation and maladaptive
      differentiation are important pathological mechanisms underlying obesity. This
      study aimed to evaluate the effects of vaspin on the proliferation and
      differentiation of preadipocyte 3T3-L1 cells and to explore the likely mechanisms
      responsible for 3T3-L1 differentiation. Vaspin was added to cultured 3T3-L1
      cells, and the differentiation of adipocytes was evaluated using Oil Red O
      staining. The AKT signaling pathway and specific differentiation factors related
      to the differentiation of preadipocyte 3T3-L1 cells, peroxisome proliferator
      activated gamma and the CCAAT/enhancer-binding protein (C/EBP) family, were
      evaluated using reverse transcription polymerase chain reaction (RT-PCR) and
      western blot analyses during the early phase of differentiation. Additionally,
      adiponectin mRNA, interleukin-6 mRNA (IL-6 mRNA), and glucose transporter-4
      (GLUT4) protein levels were measured in the differentiated adipocytes. The
      results indicated that vaspin promotes the intracellular accumulation of lipids
      and increases differentiation-related factors, including peroxisome proliferator
      activated receptor gamma, C/EBPalpha, and free fatty acid-binding protein 4
      (FABP4), in a dose-dependent manner. Additionally, vaspin (200 ng/mL) increased
      the mRNA and protein levels of C/EBPbeta, peroxisome proliferator-activated
      gamma, C/EBPalpha, and FABP4. Moreover, compared with the control, significantly
      smaller eight-day differentiated adipocytes were observed, and these cells
      exhibited decreased IL-6 mRNA and increased GLUT4 mRNA levels; these results also
      indicated the potential of vaspin to promote the insulin-mediated AKT signaling
      pathway during the early phase of differentiation. In conclusion, vaspin is able
      to promote the differentiation of 3T3-L1 preadipocytes and may increase their
      sensitivity to insulin and suppress obesity.

PMID- 25585629
TI  - Electrochemical biosensor for rapid and sensitive detection of magnetically
      extracted bacterial pathogens.
AB  - Biological defense and security applications demand rapid, sensitive detection of
      bacterial pathogens. This work presents a novel qualitative electrochemical
      detection technique which is applied to two representative bacterial pathogens,
      Bacillus cereus (as a surrogate for B. anthracis) and Escherichia coli O157:H7,
      resulting in detection limits of 40 CFU/mL and 6 CFU/mL, respectively, from pure
      culture. Cyclic voltammetry is combined with immunomagnetic separation in a rapid
      method requiring approximately 1 h for presumptive positive/negative results. An
      immunofunctionalized magnetic/polyaniline core/shell nano-particle (c/sNP) is
      employed to extract target cells from the sample solution and magnetically
      position them on a screen-printed carbon electrode (SPCE) sensor. The presence of
      target cells significantly inhibits current flow between the electrically active
      c/sNPs and SPCE. This method has the potential to be adapted for a wide variety
      of target organisms and sample matrices, and to become a fully portable system
      for routine monitoring or emergency detection of bacterial pathogens. 

PMID- 25585628
TI  - Graphene and other nanomaterial-based electrochemical aptasensors.
AB  - Electrochemical aptasensors, which are based on the specificity of aptamer-target
      recognition, with electrochemical transduction for analytical purposes have
      received particular attention due to their high sensitivity and selectivity,
      simple instrumentation, as well as low production cost. Aptamers are functional
      nucleic acids with specific and high affinity to their targets, similar to
      antibodies. However, they are completely selected in vitro in contrast to
      antibodies. Due to their stability, easy chemical modifications and proneness to
      nanostructured device construction, aptamer-based sensors have been incorporated
      in a variety of applications including electrochemical sensing devices. In recent
      years, the performance of aptasensors has been augmented by incorporating novel
      nanomaterials in the preparation of better electrochemical sensors. In this
      review, we summarize the recent trends in the use of nanomaterials for developing
      electrochemical aptasensors. 

PMID- 25585630
TI  - Development of chemiluminescent lateral flow assay for the detection of nucleic
      acids.
AB  - Rapid, sensitive detection methods are of utmost importance for the
      identification of pathogens related to health and safety. Herein we report the
      development of a nucleic acid sequence-based lateral flow assay which achieves a
      low limit of detection using chemiluminescence. On-membrane enzymatic signal
      amplification is used to reduce the limit of detection to the sub-femtomol level.
      To demonstrate this assay, we detected synthetic nucleic acid sequences
      representative of Trypanosoma mRNA, the causative agent for African sleeping
      sickness, with relevance in human and animal health in sub-Saharan Africa. The
      intensity of the chemiluminescent signal was evaluated by using a charge-coupled
      device as well as a microtiter plate reader. We demonstrated that our lateral
      flow chemiluminescent assay has a very low limit of detection and is easy to use.
      The limit of detection was determined to be 0.5 fmols of nucleic acid target. 

PMID- 25585631
TI  - Linking Single Domain Antibodies that Recognize Different Epitopes on the Same
      Target.
AB  - Single domain antibodies (sdAb) are the recombinantly expressed variable regions
      from the heavy-chain-only antibodies found in camelids and sharks. SdAb are able
      to bind antigens with high affinity, and most are capable of refolding after heat
      or chemical denaturation to bind antigen again. Starting with our previously
      isolated ricin binding sdAb determined to bind to four non-overlapping epitopes,
      we constructed a series of sdAb pairs, which were genetically linked through
      peptides of different length. We designed the series so that the sdAb are linked
      in both orientations with respect to the joining peptide. We confirmed that each
      of the sdAb in the constructs was able to bind to the ricin target, and have
      evidence that they are both binding ricin simultaneously. Through this work we
      determined that the order of genetically linked sdAb seems more important than
      the linker length. The genetically linked sdAb allowed for improved ricin
      detection with better limits of detection than the best anti-ricin monoclonal we
      evaluated, however they were not able to refold as well as unlinked component
      sdAb. 

PMID- 25585632
TI  - Fabrication of biocompatible, vibrational magnetoelastic materials for
      controlling cellular adhesion.
AB  - This paper describes the functionalization of magnetoelastic (ME) materials with
      Parylene-C coating to improve the surface reactivity to cellular response.
      Previous study has demonstrated that vibrating ME materials were capable of
      modulating cellular adhesion when activated by an externally applied AC magnetic
      field. However, since ME materials are not inherently biocompatible, surface
      modifications are needed for their implementation in biological settings. Here,
      the long-term stability of the ME material in an aqueous and biological
      environment is achieved by chemical-vapor deposition of a conformal Parylene-C
      layer, and further functionalized by methods of oxygen plasma etching and protein
      adsorption. In vitro cytotoxicity measurement and characterization of the
      vibrational behavior of the ME materials showed that Parylene-C coatings of 10 um
      or greater could prevent hydrolytic degradation without sacrificing the
      vibrational behavior of the ME material. This work allows for long-term
      durability and functionality of ME materials in an aqueous and biological
      environment and makes the potential use of this technology in monitoring and
      modulating cellular behavior at the surface of implantable devices feasible. 

PMID- 25585633
TI  - Poly(lactic acid)/Carbon Nanotube Fibers as Novel Platforms for Glucose
      Biosensors.
AB  - The focus of this paper is the development and investigation of properties of new
      nanostructured architecture for biosensors applications. Highly porous
      nanocomposite fibers were developed for use as active materials in biosensors.
      The nanocomposites comprised poly(lactic acid)(PLA)/multi-walled carbon nanotube
      (MWCNT) fibers obtained via solution-blow spinning onto indium tin oxide (ITO)
      electrodes. The electrocatalytic properties of nanocomposite-modified ITO
      electrodes were investigated toward hydrogen peroxide (H2O2) detection. We
      investigated the effect of carbon nanotube concentration and the time deposition
      of fibers on the sensors properties, viz., sensitivity and limit of detection.
      Cyclic voltammetry experiments revealed that the nanocomposite-modified
      electrodes displayed enhanced activity in the electrochemical reduction of H2O2,
      which offers a number of attractive features to be explored in development of an
      amperometric biosensor. Glucose oxidase (GOD) was further immobilized by drop
      coating on an optimized ITO electrode covered by poly(lactic acid)/carbon
      nanotube nanofibrous mats. The optimum biosensor response was linear up to 800 mM
      of glucose with a sensitivity of 358 nA.mM-1 and a Michaelis-Menten constant (KM)
      of 4.3 mM. These results demonstrate that the solution blow spun nanocomposite
      fibers have great potential for application as amperometric biosensors due to
      their high surface to volume ratio, high porosity and permeability of the
      substrate. The latter features may significantly enhance the field of glucose
      biosensors. 

PMID- 25585634
TI  - In-Field Implementation of a Recombinant Factor C Assay for the Detection of
      Lipopolysaccharide as a Biomarker of Extant Life within Glacial Environments.
AB  - The discovery over the past two decades of viable microbial communities within
      glaciers has promoted interest in the role of glaciers and ice sheets (the
      cryosphere) as contributors to subglacial erosion, global biodiversity, and in
      regulating global biogeochemical cycles. In situ or in-field detection and
      characterisation of microbial communities is becoming recognised as an important
      approach to improve our understanding of such communities. Within this context we
      demonstrate, for the first time, the ability to detect Gram-negative bacteria in
      glacial field-environments (including subglacial environments) via the detection
      of lipopolysaccharide (LPS); an important component of Gram-negative bacterial
      cell walls. In-field measurements were performed using the recently
      commercialised PyroGene(r) recombinant Factor C (rFC) endotoxin detection system
      and used in conjunction with a handheld fluorometer to measure the fluorescent
      endpoint of the assay. Twenty-seven glacial samples were collected from the
      surface, bed and terminus of a low-biomass Arctic valley glacier (Engabreen,
      Northern Norway), and were analysed in a field laboratory using the rFC assay.
      Sixteen of these samples returned positive LPS detection. This work demonstrates
      that LPS detection via rFC assay is a viable in-field method and is expected to
      be a useful proxy for microbial cell concentrations in low biomass environments. 

PMID- 25585635
TI  - Enzyme-gelatin electrochemical biosensors: scaling down.
AB  - In this article we investigate the possibility of scaling down enzyme-gelatin
      modified electrodes by spin coating the enzyme-gelatin layer. Special attention
      is given to the electrochemical behavior of the selected enzymes inside the
      gelatin matrix. A glassy carbon electrode was used as a substrate to immobilize,
      in the first instance, horse heart cytochrome c (HHC) in a gelatin matrix. Both a
      drop dried and a spin coated layer was prepared. On scaling down, a transition
      from diffusion controlled reactions towards adsorption controlled reactions is
      observed. Compared to a drop dried electrode, a spin coated electrode showed a
      more stable electrochemical behavior. Next to HHC, we also incorporated catalase
      in a spin coated gelatin matrix immobilized on a glassy carbon electrode. By
      spincoating, highly uniform sub micrometer layers of biocompatible matrices can
      be constructed. A full electrochemical study and characterization of the modified
      surfaces has been carried out. It was clear that in the case of catalase,
      gluteraldehyde addition was needed to prevent leaking of the catalase from the
      gelatin matrix. 

PMID- 25585636
TI  - Novel highly selective and reversible chemosensors based on dual-ratiometric
      fluorescent electrospun nanofibers with pH- and Fe(3+)-modulated multicolor
      fluorescence emission.
AB  - Novel dual-ratiometric fluorescent electrospun (ES) nanofibers featuring high
      sensitivity for pH and ferric ion (Fe(3+)) were prepared using binary blends of
      poly(2-hydroxyethyl methacrylate-co-N-methylolacrylamide-co-nitrobenzoxadiazolyl
      derivative) (poly(HEMA-co-NMA-co-NBD)) and a spirolactam rhodamine derivative
      (SRhBOH) by employing a single-capillary spinneret. The HEMA, NMA, and NBD
      moieties were designed to exhibit hydrophilic properties, chemical cross-linking,
      and fluorescence (fluorescence resonance energy transfer (FRET) donor),
      respectively. The fluorescence emission of SRhBOH was highly selective for pH and
      Fe(3+); when SRhBOH detected acidic media and Fe(3+), the spirocyclic form of
      SRhBOH, which is nonfluorescent, was transformed into the opened cyclic form and
      exhibited strong fluorescence emission. The emission colors of ES nanofibers in
      acidic or Fe(3+) aqueous solutions changed from green to red because of FRET from
      NBD (donor) to SRhBOH (acceptor). The off/on switching of the FRET process was
      modulated by adjusting the SRhBOH blending ratio, pH, and Fe(3+) concentration.
      Poly(HEMA-co-NMA-co-NBD) ES fibers blended with 20% SRhBOH showed high
      sensitivity in sensing Fe(3+) and pH because of the substantial 57 nm red shift
      in emission as well as substantial reversible dual photoluminescence. The
      prepared FRET-based dual-ratiometric fluorescent ES nanofibrous membranes can be
      used as "naked eye" sensors and have potential for application in multifunctional
      environment sensing devices. 

PMID- 25585638
TI  - Central complex and mushroom bodies mediate novelty choice behavior in
      Drosophila.
AB  - Novelty choice, a visual paired-comparison task, for the fly Drosophila
      melanogaster is studied with severely restrained single animals in a flight
      simulator. The virtual environment simulates free flight for rotation in the
      horizontal plane. The behavior has three functional components: visual azimuth
      orientation, working memory, and pattern discrimination (perception). Here we
      study novelty choice in relation to its neural substrate in the brain and show
      that it requires the central complex and, in particular, the ring neurons of the
      ellipsoid body. Surprisingly, it also involves the mushroom bodies which are
      needed specifically in the comparison of patterns of different sizes.

PMID- 25585639
TI  - Degradation of hydroxycinnamic acid mixtures in aqueous sucrose solutions by the
      Fenton process.
AB  - The degradation efficiencies and behaviors of caffeic acid (CaA), p-coumaric acid
      (pCoA), and ferulic acid (FeA) in aqueous sucrose solutions containing the
      mixture of these hydroxycinnamic acids (HCAs) were studied by the Fenton
      oxidation process. Central composite design and multiresponse surface methodology
      were used to evaluate and optimize the interactive effects of process parameters.
      Four quadratic polynomial models were developed for the degradation of each
      individual acid in the mixture and the total HCAs degraded. Sucrose was the most
      influential parameter that significantly affected the total amount of HCA
      degraded. Under the conditions studied there was a <0.01% loss of sucrose in all
      reactions. The optimal values of the process parameters for a 200 mg/L HCA
      mixture in water (pH 4.73, 25.15  degrees C) and sucrose solution (13 mass %, pH
      5.39, 35.98  degrees C) were 77% and 57%, respectively. Regression analysis
      showed goodness of fit between the experimental results and the predicted values.
      The degradation behavior of CaA differed from those of pCoA and FeA, where
      further CaA degradation is observed at increasing sucrose and decreasing solution
      pH. The differences (established using UV/vis and ATR-FTIR spectroscopy) were
      because, unlike the other acids, CaA formed a complex with Fe(III) or with
      Fe(III) hydrogen-bonded to sucrose and coprecipitated with lepidocrocite, an iron
      oxyhydroxide.

PMID- 25585640
TI  - Patulin biodegradation by marine yeast Kodameae ohmeri.
AB  - Patulin contamination of fruit- and vegetable-based products had become a major
      challenge for the food industry. Biological methods of patulin control can play
      an important role due to their safety and high efficiency. In this study, a
      strain of marine yeast with high patulin degradation ability was screened. The
      yeast was identified as Kodameae ohmeri by the BioLog identification system and
      partial 26S rRNA gene sequencing. The degradation products of patulin were
      identified as (E)- and (Z)-ascladiol through HPLC and LC-TOF/MS. High patulin
      tolerance at 100 MUg ml(-1) and a high degradation rate at 35 degrees C at a pH
      between 3 and 6 indicates the potential application of K. ohmeri for patulin
      detoxification of apple-derived products. 

PMID- 25585637
TI  - Gerosuppression in confluent cells.
AB  - The most physiological type of cell cycle arrest - namely, contact inhibition in
      dense culture - is the least densely studied. Despite cell cycle arrest,
      confluent cells do not become senescent. We recently described that mTOR (target
      of rapamycin) is inactive in contact-inhibited cells. Therefore, conversion from
      reversible arrest to senescence (geroconversion) is suppressed. I this
      Perspective, we further extended the gerosuppression model. While causing
      senescence in regular cell density, etoposide failed to cause senescence in
      contact-inhibited cells. A transient reactivation of mTOR favored geroconversion
      in etoposide-treated confluent cells. Like p21, p16 did not cause senescence in
      high cell density. We discuss that suppression of geroconversion in confluent and
      contact-inhibited cultures mimics gerosuppression in the organism. We confirmed
      that levels of p-S6 were low in murine tissues in the organism compared with
      mouse embryonic fibroblasts in cell culture, whereas p-Akt was reciprocally high
      in the organism.

PMID- 25585641
TI  - Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5
      azacytidine through enhancing p16 demethylation.
AB  - Heme oxygenase-1 was reported previously as a resistance target on acute
      myelocytic leukemia (AML). We found that HO-1 was resistant to 5-azacytidine
      (AZA) treatment of myelodysplastic syndrome (MDS), and explored further the
      relative mechanisms. Patient bone marrow mononuclear cells (n=48) diagnosed as
      different levels of MDS were collected. Cell growth was evaluated by MTT assay;
      cell cycle and apoptosis were detected by flow cytometry; mRNA expression was
      assessed by real-time PCR, protein expression was analyzed through western
      blotting. Methylation was assessed by MSP. The survival time, and weight of mice
      were recorded. HO-1 overexpression was observed in SKM-1 cells after AZA
      treatment comparing to other cell lines. The HO-1 expression in MDS patients with
      high-risk was higher than in low-risk patients. After HO-1 was silenced by
      lentivirus-mediated siRNA, the proliferation of SKM-1 cells was effectively
      inhibited by low concentration AZA, and the cell cycle was arrested in the G0/G1
      phase. Upregulation of p16 and changing of p16-relative cell cycle protein was
      observed after silencing HO-1 in AZA treated SKM-1 cells. In addition, DNMT1 was
      downregulated following the decrease of HO-1 expression. In vivo, silencing HO-1
      inhibited SKM-1 cell growth induced by AZA in a NOD/SCID mouse model. Silencing
      HO-1 sensitized SKM-1 cells toward AZA, which may be attributed to the influence
      of HO-1 on AZA-induced p16 demethylation. HO-1 may be one of the targets that
      enhance the therapeutic effects of AZA on MDS malignant transformation inspiring
      new treatment methods for high-risk and very high-risk MDS patients in clinical
      practice.

PMID- 25585642
TI  - Erythropoietin attenuates advanced glycation endproducts-induced toxicity of
      Schwann cells in vitro.
AB  - Advanced glycation endproducts (AGEs)-induced cytotoxicity is regarded as one of
      the main mechanisms responsible for neurological disorders. Although
      erythropoietin (EPO) is demonstrated to have neuroprotective effects in
      neurodegenerative diseases, the effects of EPO on AGEs-induced toxicity of
      Schwann cells (SCs) remain open for investigation. Primary cultured SCs isolated
      from 4 day-old Wistar rats were exposed to AGEs with or without EPO treatment for
      5 days. AGEs decreased cell viability, increased apoptotic rate, elevated
      intracellular reactive oxygen species levels, and reduced total glutathione
      levels of SCs. The AGEs-induced toxic effects on SCs were partially blocked by
      AGER siRNA or AGER inhibitor FPS-ZM1. SCs exposed to AGEs exhibited higher mRNA
      and protein levels of receptor for AGEs (AGER), EPO, and EPO receptor (EPOR).
      Exogenous EPO treatment attenuated AGEs-induced oxidative stress and apoptosis
      probably by reducing the mRNA and protein expression of AGER. The protective
      effect of EPO against AGEs-induced toxicity was blocked by EPOR siRNA. The data
      of the present study gives, for the first time, evidence of the protective
      effects of EPO on SCs with AGEs-induced oxidative stress and apoptosis. These
      results imply that EPO might be a novel valuable agent for treating AGEs-induced
      toxicity.

PMID- 25585643
TI  - Selection bias in the link between child wantedness and child survival: theory
      and data from Matlab, Bangladesh.
AB  - We examine the potential effects of selection bias on the association between
      unwanted births and child mortality from 7,942 women from Matlab, Bangladesh who
      declared birth intentions in 1990 prior to conceiving pregnancies. We explore and
      test two opposing reasons for bias in the distribution of observed births. First,
      some women who report not wanting more children could face starvation or frailty;
      and if these women are infecund, the remaining unwanted births would appear more
      healthy. Second, some women who report not wanting more children could have
      social privileges in acquiring medical services, abortion, and contraceptives;
      and if these women avoid births, the remaining unwanted births would appear less
      healthy. We find (1) no overall effect of unwantedness on child survival in rural
      Bangladesh in the 1990s, (2) no evidence that biological processes are spuriously
      making the birth cohort look more healthy, and (3) some evidence that higher
      schooling for women who avoid unwanted births is biasing the observed sample to
      make unwanted births look less healthy. Efforts to understand the effect of
      unwantedness in data sets that do not control for complex patterns of selective
      birth may be misleading and require more cautious interpretation. 

PMID- 25585645
TI  - Luminescence properties and optical absorption of X ray-irradiated KBr: Ce3(+),
      Tb(3+) crystals.
AB  - This paper reports that KBr doubly doped with Tb(3+) and Ce(3+) were prepared by
      Bridgman-Stockbarger method and characterized by Optical absorption,
      Photoluminescence (PL), Thermoluminescence (TL), Photo stimulated emission (PSL)
      and TL emission, after X-ray irradiation have been observed. The optical
      absorption measurement indicates that F and Z3 centers are formed in the crystal
      during X-ray irradiation process. It was attempted to incorporate a broad band of
      Ce(3+) sensitizer into the narrow band emission of Tb(3+) in the KBr host without
      reduction of emission intensity. Co-doping of Ce(3+) ions in KBr:Tb(3+) crystal
      showed a broad band emission due to the d-f transition of Ce(3+) and a reduction
      in the intensity of emission peaks due to (5)days -> (7)F6 transition of Tb(3+)
      when they were excited at 250 nm. These results supported that an effective
      energy transfer occurs from Ce(3+) to Tb(3+) in the KBr host. Co-doping Ce(3+)
      ions greatly intensified the excitation peak at 260 nm for the emission at 390 nm
      of Tb(3+) which means that more lattice defects, involved in the energy
      absorption and transfer to Tb(3+), are formed by the Ce(3+) co-doping. The
      integrated light intensity is two orders of magnitude higher as compared to the
      undoped samples for similar doses of irradiation and heating rate.
      Thermoluminescence process has been identified due to thermal mobilization of F
      electrons and this causes peaks at 371 K and at 427 K, 457 K in KBr: Ce(3+),
      Tb(3+) crystals. The defects generated by irradiation were monitored by optical
      absorption and trap parameters for the TL process were calculated and presented.

PMID- 25585644
TI  - The effects of mortality on fertility: population dynamics after a natural
      disaster.
AB  - Understanding how mortality and fertility are linked is essential to the study of
      population dynamics. We investigate the fertility response to an unanticipated
      mortality shock that resulted from the 2004 Indian Ocean tsunami, which killed
      large shares of the residents of some Indonesian communities but caused no deaths
      in neighboring communities. Using population-representative multilevel
      longitudinal data, we identify a behavioral fertility response to mortality
      exposure, both at the level of a couple and in the broader community. We observe
      a sustained fertility increase at the aggregate level following the tsunami,
      which was driven by two behavioral responses to mortality exposure. First,
      mothers who lost one or more children in the disaster were significantly more
      likely to bear additional children after the tsunami. This response explains
      about 13 % of the aggregate increase in fertility. Second, women without children
      before the tsunami initiated family-building earlier in communities where tsunami
      related mortality rates were higher, indicating that the fertility of these women
      is an important route to rebuilding the population in the aftermath of a
      mortality shock. Such community-level effects have received little attention in
      demographic scholarship. 

PMID- 25585646
TI  - The prognostic value of standardized reference values for speckle-tracking global
      longitudinal strain in hypertrophic cardiomyopathy.
AB  - Speckle-tracking left ventricular global longitudinal strain (GLS) assessment may
      provide substantial prognostic information for hypertrophic cardiomyopathy (HCM)
      patients. Reference values for GLS have been recently published. We aimed to
      evaluate the prognostic value of standardized reference values for GLS in HCM
      patients. An analysis of HCM clinic patients who underwent GLS was performed. GLS
      was defined as normal (more negative or equal to -16%) and abnormal (less
      negative than -16%) based on recently published reference values. Patients were
      followed for a composite of events including heart failure hospitalization,
      sustained ventricular arrhythmia, and all-cause death. The power of GLS to
      predict outcomes was assessed relative to traditional clinical and
      echocardiographic variables present in HCM. 79 HCM patients were followed for a
      median of 22 months (interquartile range 9-30 months) after imaging. During
      follow-up, 15 patients (19%) met the primary outcome. Abnormal GLS was the only
      echocardiographic variable independently predictive of the primary outcome
      [multivariate Hazard ratio 5.05 (95% confidence interval 1.09-23.4, p = 0.038)].
      When combined with traditional clinical variables, abnormal GLS remained
      independently predictive of the primary outcome [multivariate Hazard ratio 5.31
      (95 % confidence interval 1.18-24, p = 0.030)]. In a model including the
      strongest clinical and echocardiographic predictors of the primary outcome,
      abnormal GLS demonstrated significant incremental benefit for risk stratification
      [net reclassification improvement 0.75 (95 % confidence interval 0.21-1.23, p <
      0.0001)]. Abnormal GLS is an independent predictor of adverse outcomes in HCM
      patients. Standardized use of GLS may provide significant incremental value over
      traditional variables for risk stratification.

PMID- 25585648
TI  - Improving acute pain management in emergency medicine.
AB  - Undertreatment of pain (oligoanalgesia) in the emergency department is common,
      and it negatively impacts patient care. Both failure of appropriate pain
      assessment and the potential for unsafe analgesic use contribute to the problem.
      As a result, achieving satisfactory analgesia while minimizing side effects
      remains particularly challenging for emergency physicians, both in the emergency
      department and after a patient is discharged. Improvements in rapid pain
      assessment and in evaluation of noncommunicative populations may result in a
      better estimation of which patients require analgesia and how much pain is
      present. New formulations of available treatments, such as rapidly absorbed,
      topical, or intranasal nonsteroidal anti-inflammatory drug formulations or
      intranasal opioids, may provide effective analgesia with an improved risk-benefit
      profile. Other pharmacological therapies have been shown to be effective for
      certain pain modalities, such as the use of antidepressants for musculoskeletal
      pain, gamma-aminobutyric acid agonists for neuropathic and postsurgical pain,
      antipsychotics for headache, and topical capsaicin for neuropathic pain.
      Nonpharmacological methods of pain control include the use of electrical
      stimulation, relaxation therapies, psychosocial/manipulative therapies, and
      acupuncture. Tailoring of available treatment options to specific pain
      modalities, as well as improvements in pain assessment, treatment options, and
      formulations, may improve pain control in the emergency department setting and
      beyond.

PMID- 25585647
TI  - Profiling of skeletal muscle Ankrd2 protein in human cardiac tissue and neonatal
      rat cardiomyocytes.
AB  - Muscle-specific mechanosensors Ankrd2/Arpp (ankyrin repeat protein 2) and
      Ankrd1/CARP (cardiac ankyrin repeat protein) have an important role in
      transcriptional regulation, myofibrillar assembly, cardiogenesis and myogenesis.
      In skeletal muscle myofibrils, Ankrd2 has a structural role as a component of a
      titin associated stretch-sensing complex, while in the nucleus it exerts
      regulatory function as transcriptional co-factor. It is also involved in myogenic
      differentiation and coordination of myoblast proliferation. Although expressed in
      the heart, the role of Ankrd2 in the cardiac muscle is completely unknown.
      Recently, we have shown that hypertrophic and dilated cardiomyopathy pathways are
      altered upon Ankrd2 silencing suggesting the importance of this protein in
      cardiac tissue. Here we provide the underlying basis for the functional
      investigation of Ankrd2 in the heart. We confirmed reduced Ankrd2 expression
      levels in human heart in comparison with Ankrd1 using RNAseq and Western blot.
      For the first time we demonstrated that, apart from the sarcomere and nucleus,
      both proteins are localized to the intercalated disks of human cardiomyocytes. We
      further tested the expression and localization of endogenous Ankrd2 in rat
      neonatal cardiomyocytes, a well-established model for studying cardiac-specific
      proteins. Ankrd2 was found to be expressed in both the cytoplasm and nucleus,
      independently from maturation status of cardiomyocytes. In contrast to Ankrd1, it
      is not responsive to the cardiotoxic drug Doxorubicin, suggesting that different
      mechanisms govern their expression in cardiac cells.

PMID- 25585649
TI  - Predictive tissue biomarkers for bevacizumab-containing therapy in metastatic
      colorectal cancer: an update.
AB  - Bevacizumab is the first anti-angiogenic agent approved for the treatment of
      metastatic colorectal cancer. The need for patient selection before initiating
      therapy necessitates the study of various proteins expressed in metastatic
      colorectal cancer tissue as candidate predictive markers. Immunohistochemistry is
      a valuable, commonly available and cost-effective method to assess predictive
      biomarkers. However, it is subject to variations and therefore requires rigorous
      protocol standardizations. Furthermore, validated quantification methodologies to
      study these angiogenic elements have to be applied. Based on their function in
      tumor angiogenesis and their relation to the mechanism of action of bevacizumab,
      protein markers were divided in four groups: VEGF A-signaling proteins; other
      relevant angiogenesis factors; factors regarding the tumor microenvironment and
      tumor intrinsic markers. Conceivably, nimbly selecting a small but relevant group
      of therapy-guided patients by the appropriate combination of predictive
      biomarkers may confer great value to this angiogenic inhibitor. 

PMID- 25585650
TI  - Psychiatry resident-led tutorials increase medical student knowledge and improve
      national board of medical examiners shelf exam scores.
AB  - OBJECTIVES: Psychiatry residents have tremendous potential as educators. The
      authors envisioned residents as small-group tutors, efficiently assessing and
      correcting knowledge deficits using cases with discussion prompts and teaching
      points. They empirically tested whether this improves knowledge acquisition.
      METHODS: Senior residents delivered eight tutorials during clerkship, which
      covered child and adolescent psychiatry, anxiety, mood, psychotic, cognitive, and
      substance use disorders. A 50-item multiple-choice quiz was administered at the
      beginning and end of clerkship. National Board of Medical Examiners (NBME) shelf
      exam scores from intervention year were compared to the 4 years prior to resident
      involvement. RESULTS: Mean score on the initial quiz was 34.5 +/- 3.7 and 41.8 +/
      3.5 on second attempt (p < 0.001). Mean score for NBME psychiatry subject exam
      during intervention year was 83.2 +/- 8.9 and for the four prior years was 78.0
      +/- 9.3, which was significant (p = 0.002). CONCLUSIONS: Resident-led tutorials
      provide an effective means of increasing psychiatric knowledge and improving
      performance on NBME subject exams.

PMID- 25585651
TI  - Macroscopic handling and reporting of breast cancer specimens pre- and post
      neoadjuvant chemotherapy treatment: review of pathological issues and suggested
      approaches.
AB  - Neoadjuvant chemotherapy (NACT) is used increasingly in the treatment of invasive
      breast cancer and presents challenges for the pathologist in the handling and
      interpretation of tissues. Potential issues include pathological identification
      and localization of the residual tumour site; how best to assess pathological
      response (given the diversity of scoring systems described); the timing and
      assessment of axillary node biopsy; and the value of retesting any residual
      tumour for dissonance between core biopsy and post-treatment residual cancer
      cells for biomarker expression such as oestrogen and progesterone receptors and
      human epidermal growth factor receptor 2 (HER2). The role of the pathologist is
      critical in modern NACT approaches to breast cancer and is likely to remain
      challenging as novel agents and newer biomarkers become available. In this
      manuscript we review these issues and describe some practical approaches to
      handling and reporting these samples in the routine histopathology laboratory. 

PMID- 25585652
TI  - [Care concepts in mass casualty incidents and disasters. Concept for primary care
      clinic].
AB  - BACKGROUND: Patient care in mass casualty incidents and disaster strongly demand
      a joint approach of all preclinical and clinical forces. OBJECTIVE: Special
      emphasis must be placed on immediate triage, establishment and preservation of
      transportability of high-risk patients and their clinical treatment as soon as
      possible. During limited mass casualties, the preclinical rescue station
      additionally serves as a buffer for patients, whereby in case of disaster, the
      focus on transportation of high-risk patients is imperative. DISCUSSION AND
      CONCLUSION: Primary care hospitals are a decisive part in the chain of medical
      supply and are confronted with great challenges, which demand detailed emergency
      plans and also repeated exercises. In planning and exercises, special attention
      should be given to the cooperation with the fire department and other medical
      services.

PMID- 25585653
TI  - [Isoflurane-induced malignant hyperthermia during intensive-care treatment].
AB  - Malignant hyperthermia (MH), an inherited myopathia varying in severity and
      course, is induced by halogenated anesthetic agents and depolarizing muscle
      relaxants. First recognized as a distinct disease entity in 1960, MH is defined
      as an anesthesia-related disease due to the agents by which it is triggered.
      Given the wide use of these preparations in prehospital emergency medicine and
      intensive care treatment, physicians in other disciplines may also encounter MH. 

PMID- 25585654
TI  - Radiotherapy effects on early breast cancer survival in observational and
      randomized studies: a systematic analysis of advantages, disadvantages and
      differences between the two study types.
AB  - AIM: Treatment-outcome associations often differ substantially between
      observational studies (OSs) and randomized controlled trials (RCTs). We
      investigate causes, focusing on radiotherapy (RT) effects in early breast cancer
      treatment, to better understand each study type's merits. METHODS AND MATERIALS:
      We systematically analyzed three potential causes, by comparing data from a large
      OS with results from two previously published meta-analyses of RCTs: differences
      in patient populations combined with heterogeneous treatment effects, non-random
      treatment decisions in OSs, and differences in therapy administration. RESULTS:
      RT-survival associations were considerably stronger in our OS than in the RCTs,
      e.g., a hazard rate for overall survival after breast-conserving therapy of 0.57
      in the OS vs 0.90 in the RCTs. The first proposed reason has limited relevance:
      patient populations differed considerably, but effect heterogeneity between
      patient groups was limited. The second reason does explain part of the
      difference: in the OS treatment decisions (being nonrandomized) and prospects
      differed with patient characteristics. Notably, patients with early recurrences
      or mortality are generally excluded from RCTs. Their inclusion in OSs leads to
      stronger treatment-outcome associations. CONCLUSION: RCTs and OSs each have their
      own merits. While RCTs have their undisputed benefits, results from OSs that
      indicate that RT effects in early breast cancer are even stronger than those
      reported in RCTs should not be ignored.

PMID- 25585655
TI  - The effectiveness of simultaneous oncoplastic breast surgery in patients with
      locally advanced breast cancer.
AB  - BACKGROUND: Oncological outcomes of the oncoplastic breast surgery in patients
      with locally advanced breast cancer (LABC) are not well defined. This study
      examined the effects of oncoplastic techniques for LABC in terms of localized
      control and survival. We also evaluated the esthetic results of patients who had
      undergone oncoplastic breast conservation surgery (OBCS) and their satisfaction
      with the outcome. METHODS: The files and Medula (Probel Co.) database records of
      the patients were studied retrospectively. The esthetic evaluation was conducted
      by a panel. A validated satisfaction study was also performed. RESULTS: In total,
      42 LABC cases (median age 48 years; range 33-69 years) were included. The median
      observation period was 61 months (range 26-151 months). Neoadjuvant chemotherapy
      (NACT) was administered in 32 (76%) cases, and a pathologic complete response was
      observed in 7 (16.7%) cases. The median T size during the post-NACT pathological
      study was 27 mm (range 0-44 mm). Oncoplastic reduction surgery was performed in
      13 cases, a glandular flap in 7, Grisotti flap in 5, and latissimus dorsi flap in
      3 cases. The median specimen weight was 198 g (range 103-812 g), and the mean
      surgical margin length was 8.7 mm (range 5-17 mm). The margin was positive in
      7.1% of cases, and the local repetition rate was 14.6%. The total survival rate
      was 86.6%, and disease-free survival was 59.6%. The rate of excellent and good
      ratings by the esthetic assessment panel was 79.4%. The satisfaction rate was
      88.2%. The early and delayed complication rate was 16.7%. CONCLUSIONS:
      Oncoplastic techniques are suitable and safe for patients undergoing OBCS. These
      techniques do not pose a risk to oncological local control. No survival or follow
      up problems were detected during the 5-year follow-up period, the esthetic
      results were acceptable, and the satisfaction rate was high.

PMID- 25585656
TI  - Evaluation of a new balloon occlusion catheter specifically designed for
      measurement of hepatic venous pressure gradient.
AB  - BACKGROUND & AIMS: Despite the important clinical value of hepatic venous
      pressure gradient (HVPG) and its increasing use, no specific balloon occlusion
      catheters have been designed to cannulate liver veins. The aim of the study was
      to evaluate the clinical applicability of a novel balloon (NC) occlusion catheter
      specifically designed for HVPG measurement. METHODS: Comparison of a new CE
      certified 7 French balloon occlusion catheter with a 150 degrees  angled tip and
      radiopaque markers (NC, Pejcl Medizintechnik, Austria), to a commonly used
      straight balloon catheter (SC; Boston Scientific, USA). Successful liver vein
      cannulation rate, need for extra equipment and total fluoroscopy time were
      recorded. Experts (>200) and novices (<20) in HVPG measurements were evaluated
      separately. RESULTS: 566 HVPG measurements taken by 11 investigators (five
      experts and six novices) were analysed. Overall, HVPG could be successfully
      measured in 98.7% of cases. The rate of successful liver vein cannulation at
      first attempt was significantly higher among experts when compared to novices
      (87.3% vs 67.3%, P < 0.001). Moreover, the rate of successful liver vein
      cannulation without need for any additional equipment was higher when using the
      NC, both among experts (NC:91.9% vs SC:80.6%, P = 0.03) and novices (NC:73.3% vs
      SC:50.7%, P = 0.001). The mean fluoroscopy time needed to cannulate the hepatic
      vein was significantly shorter in experts as compared to novices [2.37(0.10-26)
      vs 5.2(0.6-30.2] min, P < 0.0001), but not significantly different between
      catheters. CONCLUSIONS: Both novices and experts achieve higher liver vein
      cannulation rates using the new specifically designed catheter. The use of the
      novel catheter might increase rates of successful liver vein cannulation and
      reduce the need for additional equipment, especially in novices.

PMID- 25585657
TI  - Electro-resistive bands for non-invasive cardiac and respiration monitoring, a
      feasibility study.
AB  - Continuous unobtrusive monitoring of tidal volume, particularly for critical care
      patients (i.e. neonates and patients in intensive care) during sleep studies and
      during daily activities, is still an unresolved monitoring need. Also a
      successful monitoring solution is yet to be proposed for continuous non-invasive
      cardiac stroke volume monitoring that is a novel clinical need.In this paper we
      present the feasibility study for a wearable, non-invasive, non-contact and
      unobtrusive sensor (embedded in a standard T-shirt) based on four electro
      resistive bands that simultaneously monitors tidal volume and cardiac stroke
      volume changes. This low power sensor system (requires only 100 mW and accepts a
      wide power supply range up to +/-18 V); thus the sensor can be easily embedded in
      existing wearable solutions (i.e. Holter monitors). Moreover, being contactless,
      it can be worn over bandages or electrodes, and as it does not rely over the
      integrity of the garment to work, it allows practitioners to perform procedures
      during monitoring. For this preliminary evaluation, one subject has worn the
      sensor over the period of 24 h (removing it only to shower); the accuracy of the
      tidal volume tested against a portable spirometer reported a precision of +/-10%
      also during physical activity; accuracy tests for cardiac output (as it may
      require invasive procedure) have not been carried out in this preliminary trial. 

PMID- 25585659
TI  - Use of a quantitative platelet function test to guide epidural catheter removal
      in a patient who inadvertently received clopidogrel.

PMID- 25585660
TI  - Late two-stage laparoscopic cholecystectomy is associated with an increased risk
      of major bile duct injury.
AB  - BACKGROUND: Late laparoscopic cholecystectomy (LC) after endoscopic retrograde
      cholangiopancreatography (ERCP) and sphincterotomy (ES) for common bile duct
      (CBD) stone clearance, two-stage LC (TSLC), is associated with difficult surgical
      dissection and an increased rate of conversion to open procedure. The purpose of
      the study was to evaluate whether the interval between ERCP/ES and LC is
      associated with major bile duct injury (BDI) and determine an optimal period for
      TSLC. METHODS: This was a retrospective cohort study of adult patients who
      underwent LC. The exclusion criteria were absence of CBD stones on imaging or
      ERCP, surgical treatment of choledocholithiasis, post-operative endoscopic CBD
      stone clearance and open cholecystectomy. RESULTS: The eligibility criteria were
      met by 183 patients. There were six major BDIs (3%). Comparisons of the early and
      late TSLC showed statistically significant difference in major BDI at 16-week cut
      offs. Binomial regression analysis demonstrated that late (>=16 weeks) TSLC was
      associated with 10-fold increase in major BDI (95% confidence interval: 1.1-95.7,
      P = 0.043). Survival analysis comparing early (<16 weeks) with late (>=16 weeks)
      TSLC demonstrated that both groups had similar survival time (log-rank test:
      0.317). CONCLUSION: General surgeons should be aware of the increasing risk of
      major BDI with delaying TSLC and perform interval LC before week 16.

PMID- 25585658
TI  - Molecular Detection of Helicobacter pylori and its Antimicrobial Resistance in
      Brazzaville, Congo.
AB  - BACK GROUND: Helicobacter pylori infection is involved in several gastroduodenal
      diseases which can be cured by antimicrobial treatment. The aim of this study was
      to determine the prevalence of H. pylori infection and its bacterial resistance
      to clarithromycin, fluoroquinolones, and tetracycline in Brazzaville, Congo, by
      using molecular methods. MATERIAL AND METHODS: A cross- sectional study was
      carried out between September 2013 and April 2014. Biopsy specimens were obtained
      from patients scheduled for an upper gastrointestinal endoscopy and were sent to
      the French National Reference Center for Campylobacters and Helicobacters where
      they were tested by molecular methods for detection of H. pylori and
      clarithromycin resistance by real-time PCR using a fluorescence resonance energy
      transfer-melting curve analysis (FRET-MCA) protocol, for detection of
      tetracycline resistance by real-time PCR on 16S rRNA genes (rrnA and rrnB), for
      detection of point mutations in the quinolone resistance-determining regions
      (QRDR) of H. pylori gyrA gene, associated with resistance to quinolones, by PCR
      and sequencing. RESULTS: This study showed a high H. pylori prevalence (89%), low
      rates of clarithromycin and tetracycline resistance (1.7% and 2.5%,
      respectively), and a high rate of quinolone resistance (50%). CONCLUSION:
      Therefore, the use of standard clarithromycin-based triple therapy is still
      possible as an empiric first-line treatment as well as prescription of bismuth
      based quadruple therapy, which includes tetracycline, but not a levofloxacin
      based triple therapy because of the high rate of resistance to fluoroquinolones.

PMID- 25585661
TI  - RNA complex purification using high-affinity fluorescent RNA aptamer tags.
AB  - RNA plays important roles in cellular processes, but RNA-protein complexes are
      notoriously hard to isolate and study. We compare and contrast existing RNA- and
      protein-purification strategies with the potential of new RNA-tagging systems
      such as RNA Spinach and RNA Mango. Each RNA aptamer binds a small fluorophore,
      resulting in a highly fluorescent complex that is thousands of times brighter
      than the unbound fluorophore. Provided that the aptamer binding affinity is high
      enough, derivatized dyes can be used in conjunction with these aptamers to purify
      RNA complexes while simultaneously using their intrinsic fluorescence to track
      the complex of interest. The known strengths and weakness of these RNA tagging
      systems are discussed.

PMID- 25585662
TI  - Planarian myosin essential light chain is involved in the formation of brain
      lateral branches during regeneration.
AB  - The myosin essential light chain (ELC) is a structure component of the actomyosin
      cross-bridge, however, the functions in the central nervous system (CNS)
      development and regeneration remain poorly understood. Planarian Dugesia japonica
      has revealed fundamental mechanisms and unique aspects of neuroscience and
      neuroregeneration. In this study, the cDNA DjElc, encoding a planarian essential
      light chain of myosin, was identified from the planarian Dugesia japonica cDNA
      library. It encodes a deduced protein with highly conserved functionally domains
      EF-Hand and Ca(2+) binding sites that shares significant similarity with other
      members of ELC. Whole mount in situ hybridization studies show that DjElc
      expressed in CNS during embryonic development and regeneration of adult
      planarians. Loss of function of DjElc by RNA interference during planarian
      regeneration inhibits brain lateral branches regeneration completely. In
      conclusion, these results demonstrated that DjElc is required for maintenance of
      neurons and neurite outgrowth, particularly for involving the brain later branch
      regeneration.

PMID- 25585663
TI  - Isolation of candidate genes for the barley Ant1 and wheat Rc genes controlling
      anthocyanin pigmentation in different vegetative tissues.
AB  - MYB transcription factors exist in a large copy number and control various plant
      phenotypes. We cloned R2R3 MYB-type transcription factors that determine the
      coloration of basal sheaths in barley and wheat coleoptiles. These genes are
      highly homologous to maize C1 and rice OsC1, regulators for anthocyanin
      biosynthesis, but they control seed pigmentation in maize and rice. On the basis
      of high homology, barley and wheat counterparts are designated HvC1 and TaC1,
      respectively. HvC1 gene is located on the short arm of chromosome 7H, and TaC1
      genes are located on the short arms of chromosomes 7A, 7B, and 7D (TaC1-A1, B1,
      and D1, respectively). HvC1 is a strong candidate for Ant1 because of (1)
      complete co-segregation of anthocyanin pigmentation phenotype of the basal sheath
      with the HvC1 genotype in genetic mapping, and (2) complete deletion of the HvCl
      gene in two anthocyanin-decreased allelic mutants (ant1.1 and ant1.2) that were
      induced by irradiation. In contrast, colorless coleoptile wheat lines had lesions
      in all three genomes consisting of a single-nucleotide substitution or a 1-bp
      deletion of TaC1-A1, a 1.7-kb insertion of TaC1-B1, and a 2.0-kb insertion of
      TaC1-D1. At least one normal TaC1 gene appears to be sufficient to produce
      anthocyanin pigments in wheat coleoptiles. Previous crossing experiments
      localized Rc (red coleoptile) genes to homoeologous group 7 chromosomes and
      deduced Rc genotypes of several wheat lines. Their TaC1 gene sequence variation
      coincided with deduced Rc genotypes; therefore, the present molecular genetic
      study demonstrates that TaC1 is a strong candidate for Rc in wheat.

PMID- 25585665
TI  - Melanoma tumors frequently acquire LRP2/megalin expression, which modulates
      melanoma cell proliferation and survival rates.
AB  - We show that the multiligand receptor megalin, known to mediate uptake and
      trafficking of nutrients and signaling molecules, is frequently expressed in
      malignant melanoma samples. Expression of megalin-encoding mRNA was investigated
      in 65 samples of nevi, melanomas, and melanoma metastases and was observed in
      more than 60% of the malignant samples, while only in 20% of the benign
      counterparts. Megalin expression in nevus and melanoma samples was additionally
      investigated by immunohistochemistry, which confirmed our mRNA-based
      observations. We furthermore show that a panel of tumor-derived melanoma cell
      lines express LRP2/megalin endogenously. In these cells, megalin is internalized
      from the cell surface and localizes extensively to intracellular vesicles,
      confirming receptor activity and pointing toward association with the endocytic
      apparatus. Groundbreaking, our results indicate that sustained megalin expression
      in melanoma cells is crucial for cell maintenance, as siRNA-mediated reduction in
      melanoma cell expression of LRP2/megalin significantly decreases melanoma cell
      proliferation and survival rates. 

PMID- 25585664
TI  - Efficacy of etravirine combined with darunavir or other ritonavir-boosted
      protease inhibitors in HIV-1-infected patients: an observational study using
      pooled European cohort data.
AB  - OBJECTIVES: This observational study in antiretroviral treatment-experienced, HIV
      1-infected adults explored the efficacy of etravirine plus darunavir/ritonavir
      (DRV group; n = 999) vs. etravirine plus an alternative boosted protease
      inhibitor (other PI group; n = 116) using pooled European cohort data. METHODS:
      Two international (EuroSIDA; EUResist Network) and five national (France, Italy,
      Spain, Switzerland and UK) cohorts provided data (collected in 2007-2012).
      Stratum-adjusted (for confounding factors) Mantel-Haenszel differences in
      virological responses (viral load < 50 HIV-1 RNA copies/mL) and odds ratios (ORs)
      with 95% confidence intervals (CIs) were derived. RESULTS: Baseline
      characteristics were balanced between groups except for previous use of
      antiretrovirals (>= 10: 63% in the DRV group vs. 49% in the other PI group),
      including previous use of at least three PIs (64% vs. 53%, respectively) and mean
      number of PI resistance mutations (2.3 vs. 1.9, respectively). Week 24 responses
      were 73% vs. 75% (observed) and 49% vs. 43% (missing = failure), respectively.
      Week 48 responses were 75% vs. 73% and 32% vs. 30%, respectively. All 95% CIs
      around unadjusted and adjusted differences encompassed 0 (difference in
      responses) or 1 (ORs). While ORs by cohort indicated heterogeneity in response,
      for pooled data the difference between unadjusted and adjusted for cohort ORs was
      small. CONCLUSIONS: These data do not indicate a difference in response between
      the DRV and other PI groups, although caution should be applied given the small
      size of the other PI group and the lack of randomization. This suggests that the
      efficacy and virology results from DUET can be extrapolated to a regimen of
      etravirine with a boosted PI other than darunavir/ritonavir.

PMID- 25585666
TI  - Assessment of maceration techniques used to remove soft tissue from bone in cut
      mark analysis.
AB  - Maceration techniques employed in forensics must be effective without
      compromising the bone's integrity and morphology, and prevent destruction of
      evidence. Techniques must also be fast, safe, easily obtainable and inexpensive;
      not all techniques currently employed are appropriate for forensic use. To
      evaluate the most suitable approach, seven techniques including current and new
      methodologies were applied to fresh, fleshed porcine ribs exhibiting cut marks. A
      sample size of 30 specimens per technique was examined under scanning electron
      microscopy at the cut mark and the surrounding uncompromised regions; a scoring
      system of effectiveness was applied. The previously unpublished microwave method
      fared best for bone and cut mark preservation. Sodium hypochlorite destroyed cut
      marks, and was deemed unsuitable for forensic analysis. No single technique
      fulfilled all criteria; however, this study provides a benchmark for forensic
      anthropologists to select the most appropriate method for their situation, while
      maintaining the high standards required by forensic science. 

PMID- 25585667
TI  - Commentary on: Alberink I, de Jongh A, Rodriguez C. Fingermark evidence
      evaluation based on automated fingerprint identification system matching scores:
      the effect of different types of conditioning on likelihood ratios. J Forensic
      Sci 2014; 59(1):70-81.

PMID- 25585668
TI  - Authors' response.

PMID- 25585669
TI  - Commentary on: Ragavendra TR, Mhaske S, Gouraha A, Yuwanathi M, Kamath KP,
      Saawarn S, Kasetty S. Quick response code in acrylic denture: will it respond
      when needed? J Forensic Sci 2014;59:514-6.

PMID- 25585670
TI  - Letter to the editor--Paleoembryologic findings from an Institute of Legal
      Medicine: immunohistochemistry can still be carried out on vintage specimens.

PMID- 25585671
TI  - Psychometric Properties and Responsiveness to Change of 15- and 28-Item Versions
      of the SCORE: A Family Assessment Questionnaire.
AB  - The SCORE (Systemic Clinical Outcome and Routine Evaluation) is a 40-item
      questionnaire for completion by family members 12 years and older to assess
      outcome in systemic therapy. This study aimed to investigate psychometric
      properties of two short versions of the SCORE and their responsiveness to
      therapeutic change. Data were collected at 19 centers from 701 families at
      baseline and from 433 of these 3-5 months later. Results confirmed the three
      factor structure (strengths, difficulties, and communication) of the 15- and 28
      item versions of the SCORE. Both instruments had good internal consistency and
      test-retest reliability. They also showed construct and criterion validity,
      correlating with measures of parent, child, and family adjustment, and
      discriminating between clinical and nonclinical cases. Total and factor scales of
      the SCORE-15 and -28 were responsive to change over 3-5 months of therapy. The
      SCORE-15 and SCORE-28 are brief psychometrically robust family assessment
      instruments which may be used to evaluate systemic therapy.

PMID- 25585672
TI  - Obsessive-compulsive behaviour related cutaneous ulcers: two cases with
      therapeutic considerations.
AB  - Obsessive-compulsive-related cutaneous disease most often includes
      trichotillomania, neurotic excoriations and nail biting. In this report, we
      present two cases of self-inflicted severe wounds that were diagnosed as
      secondary to obsessive-compulsive behaviour. Patients were middle-aged females
      who presented with deep cutaneous ulcers that were acknowledgedly maintained
      through repetitive manipulation. Obsessive-compulsive-related cutaneous disease
      is better treated with serotonin reuptake inhibitor antidepressants in higher
      dosages than those used to treat depression. Both patients were treated with
      fluoxetine 60-80 mg that resulted in adequate healing of the ulcers; relapses
      were observed during attempts to taper fluoxetine dosage. An adequate psychic
      diagnosis is required if an effective therapeutic response to self-inflicted
      cutaneous lesions is desired, because clinically identical lesions can also be
      caused as a result of distinct mental mechanisms: anxiety, depression, psychosis,
      obsessive-compulsive disorder and classic dermatitis artefacta. 

PMID- 25585673
TI  - AEF1/MPR25 is implicated in RNA editing of plastid atpF and mitochondrial nad5,
      and also promotes atpF splicing in Arabidopsis and rice.
AB  - RNA editing is an essential mechanism that modifies target cytidines to uridine
      in both mitochondrial and plastid mRNA. Target sites are recognized by
      pentatricopeptide repeat (PPR) proteins. Using bioinformatics predictions based
      on the code describing sequence recognition by PPR proteins, we have identified
      an Arabidopsis editing factor required for editing of atpF in plastids. A loss-of
      function mutation in ATPF EDITING FACTOR 1 (AEF1, AT3G22150) results in severe
      variegation, presumably due to decreased plastid ATP synthase levels. Loss of
      editing at the atpF site is coupled with a large decrease in splicing of the atpF
      transcript, even though the editing site is within an exon and 53 nucleotides
      distant from the splice site. The rice orthologue of AEF1, MPR25, has been
      reported to be required for editing of a site in mitochondrial nad5 transcripts,
      and we confirm that editing of the same site is affected in the Arabidopsis aef1
      mutant. We also show that splicing of chloroplast atpF transcripts is affected in
      the rice mpr25 mutant. AEF1 is thus highly unusual for an RNA editing specificity
      factor in that it has functions in both organelles. 

PMID- 25585675
TI  - Endoscopic versus surgical cystogastrostomy for pancreatic pseudocysts.

PMID- 25585674
TI  - Interactions of pre-symbolic children with developmental disabilities with their
      mothers and siblings.
AB  - BACKGROUND: Depending on the severity of their disabilities, children with Down
      syndrome (DS) and with cerebral palsy (CP) may remain pre-symbolic for prolonged
      periods of time. When interacting with pre-symbolic children, communication
      partners have a role in identifying which of their behaviours are communicative,
      to be able to respond to those behaviours and maintain reciprocal interaction. To
      date, most research on these children's communication development has been
      conducted within the context of mother-child interaction. Seldom have they been
      observed interacting with other family members, and in interactions other than
      dyadic, despite these interactions also occurring daily. AIMS: To explore and
      compare the interaction of mothers and siblings with pre-symbolic children with
      DS and with CP in dyadic and triadic contexts. METHODS & PROCEDURES: Twelve pre
      symbolic children with DS (aged 1;10-5;04 years) and 12 with CP (aged 1;09-5;07
      years), and their mothers and siblings participated in this study. They were
      recruited from early intervention centres from the West Coast of Peninsular
      Malaysia. Children were observed as they engaged in three play interactions:
      mother-child, sibling-child and mother-sibling-child (triadic). OUTCOMES &
      RESULTS: Children produced the most pre-symbolic communicative behaviours during
      mother-child, followed by triadic and lastly sibling-child interaction,
      suggesting that the mother's presence encouraged children to communicate. Mothers
      created a more facilitative communication environment for the children than did
      siblings, by directing high rates of initiations towards them and by taking turns
      that paved the way for the child's next turn. Although siblings' low rates of
      interaction did not provide children with as many opportunities to produce
      communicative behaviours, it encouraged them to produce high proportions of
      initiations. During triadic interaction, mothers and siblings had to direct
      interaction towards two communication partners, causing them to direct less
      interaction towards the children with DS or CP. There was no significant
      difference in mother and sibling responsiveness to children's communicative
      behaviours across interactions and disability types, suggesting that mothers and
      siblings might have adapted to the children's various early communicative
      behaviours. CONCLUSIONS & IMPLICATIONS: From this study, it was evident that
      mothers and siblings of pre-symbolic children with DS and with CP engaged them in
      reciprocal interaction. Findings on how mothers and siblings influence pre
      symbolic children's communication suggest the need to involve them in assessment
      and intervention for these children.

PMID- 25585676
TI  - Optometrists show rudimentary understanding of evidence-based practice but are
      ready to embrace it: can barriers be overcome?
AB  - BACKGROUND: Evidence-based practice (EBP) involves integration of the best
      available evidence from research, the patient's preferences or circumstances, the
      clinical environment and the health practitioner's expertise. There have been
      several qualitative studies of EBP in health-care but none has focused on the
      profession of optometry. Therefore, the aim of the present study was to assess
      optometrists' perceptions of EBP in optometry. METHODS: This exploratory
      qualitative study employed focus group meetings and individual telephone
      interviews to gauge understanding of and opinions about EBP in a convenience
      sample of Australian and Saudi Arabian optometrists. Results were summarised in
      accordance with the Consolidated Criteria for Reporting Qualitative Research
      (COREQ) checklist. NVivo software was used for qualitative analysis of the
      results. RESULTS: Most participants were supportive of EBP; however, their
      perceptions did not generally reflect a deep understanding of the definition or
      process of EBP. Participants reported using a combination of low and high level
      evidence to inform their clinical decisions. In line with findings from other
      health professions, barriers included lack of time and lack of access to
      information, while enablers such as education, organisational support and self
      motivation were cited. DISCUSSION: Our findings suggest a need for better
      training of optometrists in EBP as well as resources and approaches that support
      EBP in optometry, such as an EBP database of pre-appraised evidence and more
      secondary sources of evidence, such as systematic reviews and critically
      appraised topics.

PMID- 25585677
TI  - Influence of surface treatments on bond strength of metal and ceramic brackets to
      a novel CAD/CAM hybrid ceramic material.
AB  - This study evaluated the effect of four different surface treatments methods on
      the shear bond strength (SBS) of ceramic and metal brackets to Vita Enamic (VE)
      CAD/CAM hybrid ceramic. A total of 240 plates (10 mm * 10 mm * 3 mm) were cut
      from VE ceramic blocks and divided into two groups. In each group, four subgroups
      were prepared by hydrofluoric acid (HF); phosphoric acid (H3PO4); diamond ceramic
      grinding bur; and silica coating using CoJet system (CJ). Maxillary central
      incisor metal (Victory Series) and ceramic (Clarity) brackets were bonded with
      light-cure composite and then stored in artificial saliva for 1 week and
      thermocycled. The SBS test was performed, and the failure types were classified
      with adhesive remnant index scores. Surface morphology of the ceramic was
      characterized after treatment using a scanning electron microscope. Data were
      analyzed using two-way ANOVA, Tukey HSD test, and Weibull analysis. SBS was
      significantly affected by the type of bracket and by type of treatment (P <
      0.001). Specimens treated with CJ presented with significantly higher SBS
      compared to other groups (P < 0.05). Improvements in SBS values (MPa) were found
      in the following order: CJ > HF > Bur > H3PO4. Ceramic bracket showed higher SBS
      compared to metal bracket. Adhesive failures between the ceramic and composite
      resin were the predominant mode of failure in all groups. Surface treatment of VE
      CAD/CAM hybrid ceramic with silica coating enhanced the adhesion with ceramic and
      metal brackets.

PMID- 25585678
TI  - Role of blood cells dynamism on hemostatic complications in low-risk patients
      with essential thrombocythemia.
AB  - Patients with essential thrombocythemia (ET) aged less than 60 years, who have
      not suffered a previous vascular event (low-risk patients), may develop
      thrombotic or hemorrhagic events. So far, it has not been possible to identify
      useful markers capable of predicting which of these patients are more likely to
      develop an event and therefore who needs to be treated. In the present study, we
      analysed the relationship between vascular complications and longitudinal blood
      counts of 136 low-risk ET patients taken over a sustained period of time (blood
      cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients
      (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A
      total number of 5,781 blood counts were collected longitudinally. Thrombotic and
      hemorrhagic events were studied together (primary endpoint) but also separately
      (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint).
      The primary endpoint showed no significant association between platelet and WBC
      count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178),
      while Hb at baseline did show an association (p = 0.024). In the dynamic analysis
      with Cox regression model, where the blood count values were studied by time of
      follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every
      increase of 1 g/dL, and that this risk then marginally decreased during follow
      up. WBC was associated with an increased risk at baseline for every increase of 1
      * 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was
      stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each
      increment at baseline of 100 * 10(9) platelets/L, HR was increased by 1.08 (95%
      CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this
      study is the first to evaluate in ET low-risk patients, the risk of developing a
      thrombotic/hemorrhagic event considering blood counts over time. Overall our
      study shows that the risk changes over time. For example, the risk associated
      with WCC is not linear as previously reported. An interesting new finding is that
      PLT and even Hb contribute to the risk of developing vascular events. Future
      treatments should take into consideration these findings and aim to control all
      parameters over time. We believe this early study may help develop a dynamic
      analysis model to predict thrombosis in the single patient. Further studies are
      now warranted to further validate our findings.

PMID- 25585680
TI  - Preclinical data reproducibility for R&D--the challenge for neuroscience.

PMID- 25585681
TI  - Reduction of alcohol drinking of alcohol-preferring (P) and high-alcohol drinking
      (HAD1) rats by targeting phosphodiesterase-4 (PDE4).
AB  - RATIONALE: Phosphodiesterase-4 (PDE4) and neuroimmune signaling have been posited
      to regulate alcohol drinking. OBJECTIVES: This study evaluated the involvement of
      PDE4 and Il22ra2 on ethanol (EtOH) intake by alcohol-preferring (P) and high
      alcohol-drinking (HAD1) rats. METHODS: Exp 1 determined the dose-response effects
      of PDE4 inhibitors, rolipram, and Ro 20-1724, on 2 h/day free-choice EtOH intake
      by adult P and HAD1 rats. Exps 2-3 examined the effects of repeated
      administration with the PDE4 inhibitors on EtOH or sucrose intake and locomotor
      behavior. Exp 4 determined Pde4-associated gene expression differences in
      subregions of the extended amygdala, between high- and low-alcohol-consuming rat
      lines. Exp 5 evaluated the effects of infusing short hairpin RNA to knock down
      Il22ra2 in the nucleus accumbens (NAc) shell on a 24-h free-choice EtOH drinking
      by P rats. RESULTS: Administration of rolipram or Ro 20-1724 reduced EtOH intake
      by P rats; Ro 20-1724 reduced EtOH intake by HAD1 rats. Repeated rolipram or Ro
      20-1724 exposure reduced EtOH intake by P and HAD1 rats. PDE4 inhibition induced
      motor impairment during the first hour of EtOH intake by P rats. Higher gene
      expression levels for PDE4A were found in the NAc shell of P vs NP rats. ShRNAs
      targeting Il22ra2 in the NAc shell significantly reduced chronic EtOH intake.
      CONCLUSIONS: PDE4 and neuroinflammatory/immune signaling pathways could represent
      molecular targets for the treatment of alcohol use disorders in genetically
      predisposed subjects. This study underscores the importance of testing compounds
      over multiple days and rat lines when determining efficacy to disrupt excessive
      alcohol intake.

PMID- 25585682
TI  - A systematic review of physiological methods in rodent pharmacological MRI
      studies.
AB  - RATIONALE: Pharmacological magnetic resonance imaging (phMRI) provides an
      approach to study effects of drug challenges on brain processes. Elucidating
      mechanisms of drug action helps us to better understand the workings of
      neurotransmitter systems, map brain function or facilitate drug development.
      phMRI is increasingly used in preclinical research employing rodent models;
      however, data interpretation and integration are complicated by the use of
      different experimental approaches between laboratories. In particular, the
      effects of different anaesthetic regimes upon neuronal and haemodynamic processes
      and baseline physiology could be problematic. OBJECTIVES: This paper investigates
      how differences in phMRI research methodologies are manifested and considers
      associated implications, placing particular emphasis on choice of anaesthetic
      regimes. METHODS: A systematic review of rodent phMRI studies was conducted.
      Factors such as those describing anaesthetic regimes (e.g. agent, dosage) and
      parameters relating to physiological maintenance (e.g. ventilatory gases) and MRI
      method were recorded. RESULTS: We identified 126 eligible studies and found that
      the volatile agents isoflurane (43.7 %) and halothane (33.3 %) were most commonly
      used for anaesthesia, but dosage and mixture of ventilatory gases varied
      substantially between laboratories. Relevant physiological parameters were
      usually recorded, although 32 % of studies did not provide cardiovascular
      measures. CONCLUSIONS: Anaesthesia and animal preparation can influence phMRI
      data profoundly. The variation of anaesthetic type, dosage regime and ventilatory
      gases makes consolidation of research findings (e.g. within a specific
      neurotransmitter system) difficult. Standardisation of a small(er) number of
      preclinical phMRI research methodologies and/or increased consideration of
      approaches that do not require anaesthesia is necessary to address these
      challenges.

PMID- 25585683
TI  - Effects of paroxetine on PTSD-like symptoms in mice.
AB  - RATIONALE: After exposure to a severe traumatic event, avoidance, fear
      sensitization, and increased anxiety are among features that can persist over
      time in people developing posttraumatic stress disorder (PTSD). Basic research on
      treatment interfering with these symptoms can provide insights to improve PTSD
      treatment. OBJECTIVES: The purposes of the present study were to induce these
      behavioral changes in mice and examine whether paroxetine would interfere with
      their expression. METHODS: Mice were submitted to avoidance training with a low
      (0.4 mA) or high (1.5 mA) foot-shock intensity, as mild and severe stressors,
      respectively, and posttraining avoidance was evaluated 1 and 12 days later. Fear
      sensitization, measured as increased freezing to a neutral tone, and enhanced
      contextual fear, measured as increased freezing to a conditioned context (wherein
      all mice received a 0.4-mA foot-shock), were assessed during this time window. An
      elevated plus maze test was also used to assess mouse anxiety-like behavior.
      RESULTS: Persistent avoidance, persistent fear sensitization, and long-term
      enhancement of contextual fear and increased anxiety-like behavior were
      established only in mice that received the 1.5-mA foot-shock during avoidance
      training. Paroxetine (at 8 mg/kg/day), injected from day 5 to day 11 after
      avoidance training, suppressed all of these behavioral changes. CONCLUSIONS:
      These data provide additional evidence for the role of paroxetine against
      expression of PTSD-like behaviors in mice.

PMID- 25585684
TI  - Rac1 expression in epithelial ovarian cancer: effect on cell EMT and clinical
      outcome.
AB  - Ras-related C3 botulinum toxin substrate 1 (rac1) has been implicated in tumor
      epithelial-mesenchymal transition (EMT); however, limited information is
      available regarding the role of rac1 in epithelial ovarian cancer (EOC). This
      study aimed to evaluate the correlation of rac1 expression with EMT and EOC
      prognosis. Rac1 protein levels of 150 EOC specimens were evaluated by
      immunohistochemical staining. Survival analysis was performed to determine the
      correlation between rac1 expression and survival. Cellular and molecular changes
      were also examined after rac1 in ovarian cancer cells was silenced in vitro and
      in vivo. The mechanism of rac1 on EMT was investigated by Western blot analysis.
      Rac1 was highly expressed in EOC. Rac1 overexpression was closely associated with
      advanced stage based on International Federation of Gynecology and Obstetrics,
      poor grade, serum Ca-125, and residual tumor size. Survival analyses demonstrated
      that patients with high rac1 expression levels were more susceptible to early
      tumor recurrence with very poor prognosis. This study revealed that rac1
      downregulation decreased cell EMT and proliferation capability in vitro and in
      vivo. Rac1 expression possibly altered cell EMT by interacting with p21-activated
      kinase 1 and p38 mitogen-activated protein kinase signaling pathways. The present
      study showed that rac1 overexpression is associated with cell EMT and poor EOC
      prognosis. Rac1 possibly plays an important role in predicting EOC metastasis. 

PMID- 25585685
TI  - An evaluation of three commercially available metal artifact reduction methods
      for CT imaging.
AB  - Three commercial metal artifact reduction methods were evaluated for use in
      computed tomography (CT) imaging in the presence of clinically realistic metal
      implants: Philips O-MAR, GE's monochromatic gemstone spectral imaging (GSI) using
      dual-energy CT, and GSI monochromatic imaging with metal artifact reduction
      software applied (MARs). Each method was evaluated according to CT number
      accuracy, metal size accuracy, and streak artifact severity reduction by using
      several phantoms, including three anthropomorphic phantoms containing metal
      implants (hip prosthesis, dental fillings and spinal fixation rods). All three
      methods showed varying degrees of success for the hip prosthesis and spinal
      fixation rod cases, while none were particularly beneficial for dental artifacts.
      Limitations of the methods were also observed. MARs underestimated the size of
      metal implants and introduced new artifacts in imaging planes beyond the metal
      implant when applied to dental artifacts, and both the O-MAR and MARs algorithms
      induced artifacts for spinal fixation rods in a thoracic phantom. Our findings
      suggest that all three artifact mitigation methods may benefit patients with
      metal implants, though they should be used with caution in certain scenarios. 

PMID- 25585686
TI  - Reproducibility and validity of an FFQ to assess usual intake of methyl-group
      donors.
AB  - OBJECTIVE: To develop and validate a novel FFQ to assess the daily intake of four
      methyl-group donors (methionine, choline, betaine and folate). DESIGN: The
      relative validity of the FFQ was assessed by comparison with 7 d estimated diet
      records (n 80) and its reproducibility was evaluated by repeated administrations
      6 weeks apart (n 92). Paired Student t tests were used to compare group means and
      de-attenuated intra-class correlations to investigate the ability of the FFQ to
      rank individuals according to their methyl-group donor intake. De-attenuated
      intra-class correlation coefficients were calculated between the test and
      reference method for methionine, choline, betaine, folate and the sum of methyl
      group donors. The weighted kappa (kappa w) was calculated as a measure of tertile
      agreement. SETTING: Flanders, Belgium. SUBJECTS: The FFQ was validated among
      Flemish women of reproductive age (18-35 years). RESULTS: The questionnaire had
      an acceptable ranking ability (r=0.32-0.68; kappa w=0.10-0.35), but overestimated
      the daily intake of folate (280.6 MUg v. 212.0 MUg) and betaine (179.1 mg v.
      147.0 mg) compared with the 7 d estimated diet record. Cross-classification
      analysis indicated that 20 % (choline) of the participants were grossly
      misclassified in the validation study. The correlation between repeated
      administrations was good (r=0.62-0.83) with a maximal misclassification of 7 %
      for betaine (kappa w=0.44-0.66). CONCLUSIONS: These results indicate that this
      newly developed FFQ is a reliable instrument with acceptable validity for ranking
      individuals according to methyl-group donor intake (except for a poor agreement
      for choline (kappa w=0.10) and a fair ranking ability for betaine (r=0.32)) in
      Flemish women of reproductive age.

PMID- 25585687
TI  - Aldehyde dehydrogenase 1: a specific cancer stem cell marker for human colorectal
      carcinoma.
AB  - Since the identification of cancer stem cells (CSCs) a new understanding of tumor
      occurrence and development has evolved. According to the stem cell (SC) theory,
      colorectal carcinoma (CRC) SCs may be derived from mutations in normal intestinal
      cells. CSCs can be defined by their cell of origin (SCs or early progenitor
      cells). Thus, through a shared stem cell marker between CSCs and SCs, it is
      possible to investigate the association between its expression and the various
      clinicopathological features in patients with CRC. Aldehyde dehydrogenase 1
      (ALDH1) is an appropriate marker. The present study was performed to examine the
      role of ALDH1 in CRC. Through indirect fluorescence antibody staining, the
      association between ALDH1 protein expression and various clinicopathological
      parameters was investigated. Furthermore, enzyme-linked immunosorbent assay
      (ELISA) was used to investigate the differing content of ALDH1 between CRC
      tissues and normal colorectal tissues. The results revealed that ALDH1 expression
      was markedly associated with tumor stage, Dukes' stage and the level of tumor
      cell differentiation. Using ELISA, it was demonstrated that there was a greater
      level of ALDH1 in CRC tissue than in normal colorectal tissue. Therefore, ALDH1
      levels can be used as a useful parameter for pathological evaluation of tissue
      histology and to predict disease prognosis.

PMID- 25585688
TI  - Mechanisms by which the N-terminal 24 amino acids of the p55 regulatory subunit
      of phosphatidylinositol 3-kinase affect endotoxin-induced cytokine release in
      human keratinocytes.
AB  - To understand the association between the cytokine network and psoriasis, the
      present study cultured human keratinocytes (HaCaT cells) and investigated the
      effects of the phosphatidylinositol-3-kinase (PI3K) p55 regulatory subunit
      (p55PIK), and its N-terminal 24 amino acids (N24) on the regulation of endotoxin
      (LPS)-induced cytokine secretion. The results of the enzyme-linked immunosorbent
      assay and reverse transcription quantitative polymerase chain reaction revealed
      an increased release of the inflammatory cytokines, tumor necrosis factor (TNF)
      alpha, interleukin (IL)-6 and IL-8 in the HaCaT cells following LPS stimulation.
      Transfection with the adenovirus (AD)-N24-green fluorescent protein (GFP)
      suppressed the release of these cytokines, whereas AD-p55PIK-GFP increased their
      release. Immunocytochemistry detected a low level of nuclear factor (NF)-kappaB
      p65 staining in quiescent HaCaT cells, which was localized primarily in the
      cytoplasm. LPS stimulation induced the translocation of NF-kappaB p65 protein
      into the nucleus and intense staining suggested increased expression.
      Transfection with AD-N24-GFP reduced the expression of NF-kappaB p65 in the
      nucleus. Western blot analysis demonstrated that AD-N24-GFP downregulated the
      expression levels of the Toll-like receptor (TLR)2/TLR4/myeloid differentiation
      factor 88 (MyD88) pathway components in the HaCaT cells, without affecting the
      PI3K/Akt signaling pathway. Transfection with AD-p55PIK-GFP resulted in an
      increased expression level of MyD88 protein and phosphorylated Akt. Co
      transfection with AD-N24-GFP and AD-p55PIK-GFP did not significantly alter the
      levels of phosphorylated extracellular-signal-regulated kinases 1/2, c-Jun N
      terminal kinases or p38, indicating that AD-N24-GFP and AD-p55PIK-GFP did not
      affect the mitogen-activated protein kinase signaling pathway. In conclusion, AD
      N24-GFP effectively inhibited the LPS-induced expression levels of TNF-alpha, IL
      6 and IL-8. The elevated expression of p55PIK synergized with LPS and promoted
      the release of inflammatory cytokines. AD-N24-GFP and AD-p55PIK-GFP affected LPS
      induced inflammatory cytokine release in the HaCaT cells through the TLRs/MyD88
      signaling pathways.

PMID- 25585689
TI  - Genome-wide association study for posthitis in the free-living population of
      European bison (Bison bonasus).
AB  - BACKGROUND: About 5-6% of the European bison (Bison bonasus) males are affected
      by posthitis (necrotic inflammation of the prepuce) and die in the wild forest.
      Despite many years of study, pathogenesis of this disease has not yet been
      determined. The main aim of the study was to find SNP markers significantly
      associated with the incidence of posthitis and mine the genome for candidate
      genes potentially involved in the development of the disease. RESULTS: It was
      shown that relatively small number of SNPs effects reached genome-wide
      significance after false discovery rate (FDR) correction. Among 25 significant
      markers, the highest effects were found for two SNPs (rs110456748 and
      rs136792896) located at the distance of 23846 bp and 37742 bp, respectively, from
      OR10A3 gene (olfactory receptor genes), known to be involved in atopic dermatitis
      in humans. It was also observed that five other significant SNP markers were
      located in the proximity of candidate genes involved in severe diseases of skin
      tissue and cancer/tumour development of epithelial or testicular germ cells,
      which suggest their potential participation in the posthitis. The 25 investigated
      SNPs showed marked differences in allelic and genotypic frequencies between the
      healthy and affected bison groups. CONCLUSIONS: The 2 Mb region of the BTA15
      chromosome is involved in genetic background of posthitis and should be closer
      examined to find causal mutations helpful in better understanding of the disease
      ethology and to control its incidence in the future.

PMID- 25585690
TI  - Glucocorticoids suppress inflammation via the upregulation of negative regulator
      IRAK-M.
AB  - Glucocorticoids are among the most commonly used anti-inflammatory agents.
      Despite the enormous efforts in elucidating the glucocorticoid-mediated anti
      inflammatory actions, how glucocorticoids tightly control overactive inflammatory
      response is not fully understood. Here we show that glucocorticoids suppress
      bacteria-induced inflammation by enhancing IRAK-M, a central negative regulator
      of Toll-like receptor signalling. The ability of glucocorticoids to suppress
      pulmonary inflammation induced by non-typeable Haemophilus influenzae is
      significantly attenuated in IRAK-M-deficient mice. Glucocorticoids improve the
      survival rate after a lethal non-typeable Haemophilus influenzae infection in
      wild-type mice, but not in IRAK-M-deficient mice. Moreover, we show that
      glucocorticoids and non-typeable Haemophilus influenzae synergistically
      upregulate IRAK-M expression via mutually and synergistically enhancing p65 and
      glucocorticoid receptor binding to the IRAK-M promoter. Together, our studies
      unveil a mechanism by which glucocorticoids tightly control the inflammatory
      response and host defense via the induction of IRAK-M and may lead to further
      development of anti-inflammatory therapeutic strategies. 

PMID- 25585692
TI  - Massive bowel resection upregulates the intestinal mRNA expression levels of
      cellular retinol-binding protein II and apolipoprotein A-IV and alters the
      intestinal vitamin A status in rats.
AB  - Short bowel (SB) syndrome causes the malabsorption of various nutrients. Among
      these, vitamin A is important for a number of physiological activities. Vitamin A
      is absorbed by epithelial cells of the small intestine and is discharged into the
      lymphatic vessels as a component of chylomicrons and is delivered to the liver.
      In the present study, we used a rat model of SB syndrome in order to assess its
      effects on the expression of genes associated with the absorption, transport and
      metabolism of vitamin A. In the rats with SB, the intestinal mRNA expression
      levels of cellular retinol-binding protein II (CRBP II, gene symbol Rbp2) and
      apolipoprotein A-IV (gene symbol Apoa4) were higher than those in the sham
      operated rats, as shown by RT-qPCR. Immunohistochemical analysis revealed that
      absorptive epithelial cells stained positive for both CRBP II and lecithin
      retinol acyltransferase, which are both required for the effective esterification
      of vitamin A. In the rats with SB, the retinol content in the ileum and the
      retinyl ester content in the jejunum were lower than those in the sham-operated
      rats, as shown by quantitative analysis of retinol and retinyl esters by high
      performance liquid chromatography. These results suggest that the elevated mRNA
      expression levels of Rbp2 and Apoa4 in the rats with SB contribute to the
      effective esterification and transport of vitamin A.

PMID- 25585691
TI  - RNA export factor Ddx19 is required for nuclear import of the SRF coactivator
      MKL1.
AB  - Controlled transport of macromolecules between the cytoplasm and nucleus is
      essential for homeostatic regulation of cellular functions. For instance, gene
      expression entails coordinated nuclear import of transcriptional regulators to
      activate transcription and nuclear export of the resulting messenger RNAs for
      cytoplasmic translation. Here we link these two processes by reporting a novel
      role for the mRNA export factor Ddx19/Dbp5 in nuclear import of MKL1, the signal
      responsive transcriptional activator of SRF. We show that Ddx19 is not a general
      nuclear import factor, and that its specific effect on MKL1 nuclear import is
      separate from its role in mRNA export. Both helicase and nuclear pore-binding
      activities of Ddx19 are dispensable for MKL1 nuclear import, but RNA binding is
      required. Mechanistically, Ddx19 operates by modulating the conformation of MKL1,
      which affects its interaction with Importin-beta for efficient nuclear import.
      Thus, Ddx19 participates in mRNA export, translation and nuclear import of a key
      transcriptional regulator.

PMID- 25585694
TI  - Reply to Stoimenis et al.

PMID- 25585693
TI  - Memristive and neuromorphic behavior in a Li(x)CoO2 nanobattery.
AB  - The phenomenon of resistive switching (RS), which was initially linked to non
      volatile resistive memory applications, has recently also been associated with
      the concept of memristors, whose adjustable multilevel resistance characteristics
      open up unforeseen perspectives in cognitive computing. Herein, we demonstrate
      that the resistance states of Li(x)CoO2 thin film-based metal-insulator-metal
      (MIM) solid-state cells can be tuned by sequential programming voltage pulses,
      and that these resistance states are dramatically dependent on the pulses input
      rate, hence emulating biological synapse plasticity. In addition, we identify the
      underlying electrochemical processes of RS in our MIM cells, which also reveal a
      nanobattery-like behavior, leading to the generation of electrical signals that
      bring an unprecedented new dimension to the connection between memristors and
      neuromorphic systems. Therefore, these LixCoO2-based MIM devices allow for a
      combination of possibilities, offering new perspectives of usage in
      nanoelectronics and bio-inspired neuromorphic circuits.

PMID- 25585695
TI  - Compound heterozygosity for KLF1 mutations is associated with microcytic
      hypochromic anemia and increased fetal hemoglobin.
AB  - Kruppel-like factor 1 (KLF1) regulates erythroid lineage commitment, globin
      switching, and the terminal maturation of red blood cells. Variants in human KLF1
      have been identified as an important causative factor in a wide spectrum of
      phenotypes. This study investigated two unrelated male children in China who had
      refractory anemia associated with poikilocythemia. These were accompanied by an
      upregulation of biochemical markers of hemolysis, along with abnormal hemoglobin
      (Hb) level and elevated reticulocyte counts. Next-generation sequencing revealed
      that the patients were compound heterozygotes for a KLF1 frameshift mutation
      c.525_526insCGGCGCC (p.(Gly176ArgfsTer179)) and one of two missense variants,
      c.892 G>C (p.(Ala298Pro)) and c.1012C>T (p.(Pro338Ser)). The subjects had
      microcytic hypochromic anemia, and their healthy parents had single mutation. The
      two missense mutations affected a highly conserved codon in the zinc finger DNA
      binding domain of KLF1, but the protein stability was unaffected in K-562 cells.
      A KLF1-targeted promoter-reporter assay showed that the two mutations reduce the
      expression of the HBB, BCL11A, and CD44 genes involved in erythropoiesis, with
      consequent dyserythropoiesis and an alpha/non-alpha chain imbalance. A systematic
      analysis was performed of the phenotypes associated with the KLF1 mutations in
      the two families, and the clinical characteristics and differential diagnoses of
      the disease are presented. This is the first report of an autosomal recessive
      anemia presenting with microcytic hypochromia, abnormal Hb profile, and other
      distinctive erythrocyte phenotypes, and provides insight into the multiple roles
      of KLF1 during erythropoiesis. 

PMID- 25585698
TI  - 'Epistatic interactions between autoimmunity and genetic thrombophilia'.

PMID- 25585696
TI  - Genome-wide analysis identifies a role for common copy number variants in
      specific language impairment.
AB  - An exploratory genome-wide copy number variant (CNV) study was performed in 127
      independent cases with specific language impairment (SLI), their first-degree
      relatives (385 individuals) and 269 population controls. Language-impaired cases
      showed an increased CNV burden in terms of the average number of events (11.28 vs
      10.01, empirical P=0.003), the total length of CNVs (717 vs 513 Kb, empirical
      P=0.0001), the average CNV size (63.75 vs 51.6 Kb, empirical P=0.0005) and the
      number of genes spanned (14.29 vs 10.34, empirical P=0.0007) when compared with
      population controls, suggesting that CNVs may contribute to SLI risk. A similar
      trend was observed in first-degree relatives regardless of affection status. The
      increased burden found in our study was not driven by large or de novo events,
      which have been described as causative in other neurodevelopmental disorders.
      Nevertheless, de novo CNVs might be important on a case-by-case basis, as
      indicated by identification of events affecting relevant genes, such as ACTR2 and
      CSNK1A1, and small events within known micro-deletion/-duplication syndrome
      regions, such as chr8p23.1. Pathway analysis of the genes present within the CNVs
      of the independent cases identified significant overrepresentation of
      acetylcholine binding, cyclic-nucleotide phosphodiesterase activity and MHC
      proteins as compared with controls. Taken together, our data suggest that the
      majority of the risk conferred by CNVs in SLI is via common, inherited events
      within a 'common disorder-common variant' model. Therefore the risk conferred by
      CNVs will depend upon the combination of events inherited (both CNVs and SNPs),
      the genetic background of the individual and the environmental factors. 

PMID- 25585697
TI  - Dominant transmission of de novo KIF1A motor domain variant underlying pure
      spastic paraplegia.
AB  - Variants in family 1 kinesin (KIF1A), which encodes a kinesin axonal motor
      protein, have been described to cause variable neurological manifestations.
      Recessive missense variants have led to spastic paraplegia, and recessive
      truncations to sensory and autonomic neuropathy. De novo missense variants cause
      developmental delay or intellectual disability, cerebellar atrophy and variable
      spasticity. We describe a family with father-to-son transmission of de novo
      variant in the KIF1A motor domain, in a phenotype of pure spastic paraplegia.
      Structural modeling of the predicted p.(Ser69Leu) amino acid change suggested
      that it impairs the stable binding of ATP to the KIF1A protein. Our study reports
      the first dominantly inherited KIF1A variant and expands the spectrum of
      phenotypes caused by heterozygous KIF1A motor domain variants to include pure
      spastic paraplegia. We conclude that KIF1A should be considered a candidate gene
      for hereditary paraplegias regardless of inheritance pattern. 

PMID- 25585699
TI  - Effects of copy number variable regions on local gene expression in white blood
      cells of Mexican Americans.
AB  - Only few systematic studies on the contribution of copy number variation to gene
      expression variation have been published to date. Here we identify effects of
      copy number variable regions (CNVRs) on nearby gene expression by investigating
      909 CNVRs and expression levels of 12059 nearby genes in white blood cells from
      Mexican-American participants of the San Antonio Family Heart Study. We
      empirically evaluate our ability to detect the contribution of CNVs to proximal
      gene expression (presumably in cis) at various window sizes (up to a 10 Mb
      distance) between the gene and CNV. We found a ~1-Mb window size to be optimal
      for capturing cis effects of CNVs. Up to 10% of the CNVs in this study were found
      to be significantly associated with the expression of at least one gene within
      their vicinity. As expected, we find that CNVs that directly overlap gene
      sequences have the largest effects on gene expression (compared with non
      overlapping CNVRs located nearby), with positive correlation (except for a few
      exceptions) between estimated genomic dosage and expression level. We find that
      genes whose expression level is significantly influenced by nearby CNVRs are
      enriched for immunity and autoimmunity related genes. These findings add to the
      currently limited catalog of CNVRs that are recognized as expression quantitative
      trait loci, and have implications for future study designs as well as for
      prioritizing candidate causal variants in genomic regions associated with
      disease.

PMID- 25585701
TI  - Reply to Sajantila and Budowle.

PMID- 25585700
TI  - Where is the causal variant? On the advantage of the family design over the case
      control design in genetic association studies.
AB  - Many associated single-nucleotide polymorphisms (SNPs) have been identified by
      association studies for numerous diseases. However, the association between a SNP
      and a disease can result from a causal variant in linkage disequilibrium (LD)
      with the considered SNP. Assuming that the true causal variant is among the
      genotyped SNPs, other authors demonstrated that the power to discriminate between
      it and other SNPs in LD is low. Here, we propose to take advantage of the
      information provided by family data to improve the inference on the causal
      variant: we exploit the linkage information provided by affected sib pairs to
      discriminate the causal variant from the associated SNPs. The family-based
      approach improves discrimination power requiring up to five times less
      individuals than its case-control equivalent. However, the main advantage of
      family design is the possibility to carry out the procedure one step further: the
      linkage information allows inference on causal variants, which are not genotyped
      but in LD with tag-SNPs displaying association, which is impossible with case
      control design. By means of Bayesian methods, we estimate the LD between the
      observed SNPs and an unobserved causal variant, as well as the allelic odds ratio
      at the unobserved causal variant. The proposed procedure is illustrated on a
      multiple sclerosis (MS) family data set including genotypes of SNPs in IL2RA,
      confirming the advantage of using a family design to identify causal variants.
      The results of our method on this data suggest the existence of two distinct
      causal variants in this gene for the MS. 

PMID- 25585702
TI  - Severe hypertriglyceridemia in a patient heterozygous for a lipoprotein lipase
      gene allele with two novel missense variants.
AB  - Rare monogenic hyperchylomicronemia is caused by loss-of-function mutations in
      genes involved in the catabolism of triglyceride-rich lipoproteins, including the
      lipoprotein lipase gene, LPL. Clinical hallmarks of this condition are eruptive
      xanthomas, recurrent pancreatitis and abdominal pain. Patients with LPL
      deficiency and severe or recurrent pancreatitis are eligible for the first gene
      therapy treatment approved by the European Union. Therefore the precise molecular
      diagnosis of familial hyperchylomicronemia may affect treatment decisions. We
      present a 57-year-old male patient with excessive hypertriglyceridemia despite
      intensive lipid-lowering therapy. Abdominal sonography showed signs of chronic
      pancreatitis. Direct DNA sequencing and cloning revealed two novel missense
      variants, c.1302A>T and c.1306G>A, in exon 8 of the LPL gene coexisting on the
      same allele. The variants result in the amino-acid exchanges p.(Lys434Asn) and
      p.(Gly436Arg). They are located in the carboxy-terminal domain of lipoprotein
      lipase that interacts with the glycosylphosphatidylinositol-anchored HDL-binding
      protein (GPIHBP1) and are likely of functional relevance. No further relevant
      mutations were found by direct sequencing of the genes for APOA5, APOC2, LMF1 and
      GPIHBP1. We conclude that heterozygosity for damaging mutations of LPL may be
      sufficient to produce severe hypertriglyceridemia and that chylomicronemia may be
      transmitted in a dominant manner, at least in some families. 

PMID- 25585703
TI  - Y-chromosome descent clusters and male differential reproductive success: young
      lineage expansions dominate Asian pastoral nomadic populations.
AB  - High-frequency microsatellite haplotypes of the male-specific Y-chromosome can
      signal past episodes of high reproductive success of particular men and their
      patrilineal descendants. Previously, two examples of such successful Y-lineages
      have been described in Asia, both associated with Altaic-speaking pastoral
      nomadic societies, and putatively linked to dynasties descending, respectively,
      from Genghis Khan and Giocangga. Here we surveyed a total of 5321 Y-chromosomes
      from 127 Asian populations, including novel Y-SNP and microsatellite data on 461
      Central Asian males, to ask whether additional lineage expansions could be
      identified. Based on the most frequent eight-microsatellite haplotypes, we
      objectively defined 11 descent clusters (DCs), each within a specific haplogroup,
      that represent likely past instances of high male reproductive success, including
      the two previously identified cases. Analysis of the geographical patterns and
      ages of these DCs and their associated cultural characteristics showed that the
      most successful lineages are found both among sedentary agriculturalists and
      pastoral nomads, and expanded between 2100 BCE and 1100 CE. However, those with
      recent origins in the historical period are almost exclusively found in Altaic
      speaking pastoral nomadic populations, which may reflect a shift in political
      organisation in pastoralist economies and a greater ease of transmission of Y
      chromosomes through time and space facilitated by the use of horses. 

PMID- 25585706
TI  - Impact of the removal of chocolate milk from school milk programs for children in
      Saskatoon, Canada.
AB  - Studies in the United States report inclusion of flavoured milk in the diets of
      children and youth improves nutrient intakes. No research has investigated the
      contribution of flavoured milk to overall milk intake or the milk preferences of
      Canadian children. The objective of the study was to measure milk consumption
      (plain milk and flavoured milk) by children in an elementary school environment
      and investigate factors contributing to milk choice. A mixed-method research
      design was applied across 6 schools for 12 weeks. Milk waste was measured in
      grades 1-8 for 12 weeks. Weeks 1-4 (phase 1) and 9-12 (phase 3) provided both
      plain milk and flavoured milk as chocolate milk while weeks 5-8 (phase 2)
      provided plain milk only. Beverage Frequency Questionnaires were used in each
      phase (in grades 5-8 only) to assess usual beverage consumption. Statistical
      nutrient modelling was conducted to determine the effects of removing chocolate
      milk during phase 2 as a milk choice. Later, focus groups were conducted with
      students in grades 5-8 to determine what influences them to choose/not choose to
      drink milk. Total milk intake decreased by 12.3% when chocolate milk was removed
      from the schools (26.6% +/- 5.2% to 14.31% +/- 1.6%, p < 0.001). Milk choice was
      influenced by environmental factors as well as taste, cost, convenience, and
      variety. Total milk intake was associated with location (p = 0.035) and cost (p <
      0.001), with rural students and/or those students receiving free milk drinking
      the greatest amount of milk. Nutrient modelling revealed chocolate milk is more
      cost-efficient and convenient at providing nutrients than alternative food/drink
      combinations. 

PMID- 25585704
TI  - Noninvasive prenatal testing using a novel analysis pipeline to screen for all
      autosomal fetal aneuploidies improves pregnancy management.
AB  - Noninvasive prenatal testing by massive parallel sequencing of maternal plasma
      DNA has rapidly been adopted as a mainstream method for detection of fetal
      trisomy 21, 18 and 13. Despite the relative high accuracy of current NIPT
      testing, a substantial number of false-positive and false-negative test results
      remain. Here, we present an analysis pipeline, which addresses some of the
      technical as well as the biologically derived causes of error. Most importantly,
      it differentiates high z-scores due to fetal trisomies from those due to local
      maternal CNVs causing false positives. This pipeline was retrospectively
      validated for trisomy 18 and 21 detection on 296 samples demonstrating a
      sensitivity and specificity of 100%, and applied prospectively to 1350 pregnant
      women in the clinical diagnostic setting with a result reported in 99.9% of
      cases. In addition, values indicative for trisomy were observed two times for
      chromosome 7 and once each for chromosomes 15 and 16, and once for a segmental
      trisomy 18. Two of the trisomies were confirmed to be mosaic, one of which
      contained a uniparental disomy cell line. As placental trisomies pose a risk for
      low-grade fetal mosaicism as well as uniparental disomy, genome-wide noninvasive
      aneuploidy detection is improving prenatal management. 

PMID- 25585705
TI  - Noninvasive prediction of shunt operation outcome in idiopathic normal pressure
      hydrocephalus.
AB  - Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by
      gait disturbance, cognitive deterioration and urinary incontinence in elderly
      individuals. These symptoms can be improved by shunt operation in some but not
      all patients. Therefore, discovering predictive factors for the surgical outcome
      is of great clinical importance. We used normalized power variance (NPV) of
      electroencephalography (EEG) waves, a sensitive measure of the instability of
      cortical electrical activity, and found significantly higher NPV in beta
      frequency band at the right fronto-temporo-occipital electrodes (Fp2, T4 and O2)
      in shunt responders compared to non-responders. By utilizing these differences,
      we were able to correctly identify responders and non-responders to shunt
      operation with a positive predictive value of 80% and a negative predictive value
      of 88%. Our findings indicate that NPV can be useful in noninvasively predicting
      the clinical outcome of shunt operation in patients with iNPH. 

PMID- 25585707
TI  - Optical Gratings Coated with Thin Si3N4 Layer for Efficient Immunosensing by
      Optical Waveguide Lightmode Spectroscopy.
AB  - New silicon nitride coated optical gratings were tested by means of Optical
      Waveguide Lightmode Spectroscopy (OWLS). A thin layer of 10 nm of transparent
      silicon nitride was deposited on commercial optical gratings by means of
      sputtering. The quality of the layer was tested by x-ray photoelectron
      spectroscopy and atomic force microscopy. As a proof of concept, the sensors were
      successfully tested with OWLS by monitoring the concentration dependence on the
      detection of an antibody-protein pair. The potential of the Si3N4 as functional
      layer in a real-time biosensor opens new ways for the integration of optical
      waveguides with microelectronics. 

PMID- 25585709
TI  - Developing a real time sensing system to monitor bacteria in wound dressings.
AB  - Infection control is a key aspect of wound management strategies. Infection
      results in chemical imbalances and inflammation in the wound and may lead to
      prolonged healing times and degradation of the wound surface. Frequent changing
      of wound dressings may result in damage to healing tissues and an increased risk
      of infection. This paper presents the first results from a monitoring system that
      is being developed to detect presence and growth of bacteria in real time. It is
      based on impedance sensors that could be placed at the wound-dressing interface
      and potentially monitor bacterial growth in real time. As wounds can produce
      large volumes of exudate, the initial system reported here was developed to test
      for the presence of bacteria in suspension. Impedance was measured using
      disposable silver-silver chloride electrodes. The bacteria Staphylococcus aureus
      were chosen for the study as a species commonly isolated from wounds. The growth
      of bacteria was confirmed by plate counting methods and the impedance data were
      analysed for discernible differences in the impedance profiles to distinguish the
      absence and/or presence of bacteria. The main findings were that the impedance
      profiles obtained by silver-silver chloride sensors in bacterial suspensions
      could detect the presence of high cell densities. However, the presence of the
      silver-silver chloride electrodes tended to inhibit the growth of bacteria. These
      results indicate that there is potential to create a real time infection monitor
      for wounds based upon impedance sensing. 

PMID- 25585710
TI  - Peroxide-dependent analyte conversion by the heme prosthetic group, the heme
      Peptide "microperoxidase-11" and cytochrome C on chitosan capped gold
      nanoparticles modified electrodes.
AB  - In view of the role ascribed to the peroxidatic activity of degradation products
      of cytochrome c (cyt c) in the processes of apoptosis, we investigate the
      catalytic potential of heme and of the cyt c derived heme peptide MP-11 to
      catalyse the cathodic reduction of hydrogen peroxide and to oxidize aromatic
      compounds. In order to check whether cyt c has an enzymatic activity in the
      native state where the protein matrix should suppress the inherent peroxidatic
      activity of its heme prosthetic group, we applied a biocompatible immobilization
      matrix and very low concentrations of the co-substrate H2O2. The biocatalysts
      were entrapped on the surface of a glassy carbon electrode in a biocompatible
      chitosan layer which contained gold nanoparticles. The electrochemical signal for
      the peroxide reduction is generated by the redox conversion of the heme group,
      whilst a reaction product of the substrate oxidation is cathodically reduced in
      the substrate indication. The catalytic efficiency of microperoxidase-11 is
      sufficient for sensors indicating HRP substrates, e.g., p-aminophenol,
      paracetamol and catechol, but also the hydroxylation of aniline and
      dehalogenation of 4-fluoroaniline. The lower limit of detection for p-aminophenol
      is comparable to previously published papers with different enzyme systems. The
      peroxidatic activity of cyt c immobilized in the chitosan layer for catechol was
      found to be below 1 per mill and for p-aminophenol about 3% as compared with that
      of heme or MP-11. 

PMID- 25585712
TI  - Structural Stability and Performance of Noble Metal-Free SnO2-Based Gas Sensors.
AB  - The structural stability of pure SnO2 nanoparticles and highly sensitive SnO2
      SiO2 nanocomposites (0-15 SiO2 wt%) has been investigated for conditions relevant
      to their utilization as chemoresistive gas sensors. Thermal stabilization by SiO2
      co-synthesis has been investigated at up to 600  degrees C determining regimes of
      crystal size stability as a function of SiO2-content. For operation up to 400 
      degrees C, thermally stable crystal sizes of ca. 24 and 11 nm were identified for
      SnO2 nanoparticles and 1.4 wt% SnO2-SiO2 nanocomposites, respectively. The effect
      of crystal growth during operation (TO = 320  degrees C) on the sensor response
      to ethanol has been reported, revealing possible long-term destabilization
      mechanisms. In particular, crystal growth and sintering-neck formation were
      discussed with respect to their potential to change the sensor response and
      calibration. Furthermore, the effect of SiO2 cosynthesis on the cross-sensitivity
      to humidity of these noble metal-free SnO2-based gas sensors was assessed. 

PMID- 25585708
TI  - Microfabricated electrochemical cell-based biosensors for analysis of living
      cells in vitro.
AB  - Cellular biochemical parameters can be used to reveal the physiological and
      functional information of various cells. Due to demonstrated high accuracy and
      non-invasiveness, electrochemical detection methods have been used for cell-based
      investigation. When combined with improved biosensor design and advanced
      measurement systems, the on-line biochemical analysis of living cells in vitro
      has been applied for biological mechanism study, drug screening and even
      environmental monitoring. In recent decades, new types of miniaturized
      electrochemical biosensor are emerging with the development of microfabrication
      technology. This review aims to give an overview of the microfabricated
      electrochemical cell-based biosensors, such as microelectrode arrays (MEA), the
      electric cell-substrate impedance sensing (ECIS) technique, and the light
      addressable potentiometric sensor (LAPS). The details in their working
      principles, measurement systems, and applications in cell monitoring are covered.
      Driven by the need for high throughput and multi-parameter detection proposed by
      biomedicine, the development trends of electrochemical cell-based biosensors are
      also introduced, including newly developed integrated biosensors, and the
      application of nanotechnology and microfluidic technology. 

PMID- 25585711
TI  - Detection of cardiac biomarkers using single polyaniline nanowire-based
      conductometric biosensors.
AB  - The detection of myoglobin (Myo), cardiac troponin I (cTnI), creatine kinase-MB
      (CK-MB), and b-type natriuretic peptide (BNP) plays a vital role in diagnosing
      cardiovascular diseases. Here we present single site-specific polyaniline (PANI)
      nanowire biosensors that can detect cardiac biomarkers such as Myo, cTnI, CK-MB,
      and BNP with ultra-high sensitivity and good specificity. Using single PANI
      nanowire-based biosensors integrated with microfluidic channels, very low
      concentrations of Myo (100 pg/mL), cTnI (250 fg/mL), CK-MB (150 fg/mL), and BNP
      (50 fg/mL) were detected. The single PANI nanowire-based biosensors displayed
      linear sensing profiles for concentrations ranging from hundreds (fg/mL) to tens
      (ng/mL). In addition, devices showed a fast (few minutes) response satisfying
      respective reference conditions for Myo, cTnI, CK-MB, and BNP diagnosis of heart
      failure and for determining the stage of the disease. This single PANI nanowire
      based biosensor demonstrated superior biosensing reliability with the feasibility
      of label free detection and improved processing cost efficiency due to good
      biocompatibility of PANI to monoclonal antibodies (mAbs). Therefore, this
      development of single PANI nanowire-based biosensors can be applied to other
      biosensors for cancer or other diseases. 

PMID- 25585713
TI  - Development of an electrochemical-based aspartate aminotransferase nanoparticle
      ir-C biosensor for screening of liver diseases.
AB  - Aspartate aminotransaminase (AST) is a hepatocelluar enzyme released into the
      bloodstream when hepatic cells are damaged, resulting in elevated blood levels of
      AST. A single use, disposable biosensor prototype, composed of catalytic iridium
      nano-particles dispersed on carbon paste, was developed to detect enzymatically
      produced H2O2 in AST-mediated reactions. This biosensor is capable of measuring
      AST levels in a phosphate buffer and undiluted human serum over the concentration
      range of 0 to 0.89 MUg/mL AST concentration (corresponding to 0-250 UL-1 specific
      activity). The biosensor operates at relatively low oxidation potential (+0.3
      volt (V) versus the printed Ag/AgCl), minimizing any potential chemical
      interference in human serum. The measurements of AST in human serum using the
      biosensor compared well with those measured by standard hospital
      spectrophotometric assays. This Ir-C biosensor may be useful for AST measurements
      in the clinical environment. 

PMID- 25585714
TI  - Wettability and surface free energy of polarised ceramic biomaterials.
AB  - The surface modification of ceramic biomaterials used for medical devices is
      expected to improve osteoconductivity through control of the interfaces between
      the materials and living tissues. Polarisation treatment induced surface charges
      on hydroxyapatite, beta-tricalcium phosphate, carbonate-substituted
      hydroxyapatite and yttria-stabilized zirconia regardless of the differences in
      the carrier ions participating in the polarisation. Characterization of the
      surfaces revealed that the wettability of the polarised ceramic biomaterials was
      improved through the increase in the surface free energies compared with
      conventional ceramic surfaces. 

PMID- 25585715
TI  - Spatial properties of odd and even low order harmonics generated in gas.
AB  - High harmonic generation in gases is developing rapidly as a soft X-ray
      femtosecond light-source for applications. This requires control over all the
      harmonics characteristics and in particular, spatial properties have to be kept
      very good. In previous literature, measurements have always included several
      harmonics contrary to applications, especially spectroscopic applications, which
      usually require a single harmonic. To fill this gap, we present here for the
      first time a detailed study of completely isolated harmonics. The contribution of
      the surrounding harmonics has been totally suppressed using interferential
      filtering which is available for low harmonic orders. In addition, this allows to
      clearly identify behaviors of standard odd orders from even orders obtained by
      frequency-mixing of a fundamental laser and of its second harmonic. Comparisons
      of the spatial intensity profiles, of the spatial coherence and of the wavefront
      aberration level of 5omega at 160 nm and 6omega at 135 nm have then been
      performed. We have established that the fundamental laser beam aberrations can
      cause the appearance of a non-homogenous donut-shape in the 6omega spatial
      intensity distribution. This undesirable effect can be easily controlled. We
      finally conclude that the spatial quality of an even harmonic can be as excellent
      as in standard generation.

PMID- 25585716
TI  - 2-(2-oxo-morpholin-3-yl)-acetamide derivatives as broad-spectrum antifungal
      agents.
AB  - From a fungicidal screen, we identified 2-(2-oxo-morpholin-3-yl)-acetamide
      derivatives as fungicidal agents against Candida species, additionally
      characterized by antifungal activity against Aspergillus species. However,
      development of this series was hampered by low plasmatic stability. Introduction
      of a gem-dimethyl on the 6-position of the morpholin-2-one core led to
      considerable improvement in plasmatic stability while maintaining in vitro
      antifungal activity. Further optimization of the series resulted in the discovery
      of N-(biphenyl-3-ylmethyl)-2-(4-ethyl-6,6-dimethyl-2-oxomorpholin-3-yl)acetamide
      (87), which, in addition to fungicidal activity against Candida species, shows
      promising and broad antifungal in vitro activity against various fungi species,
      such as molds and dermatophytes. In vivo efficacy was also demonstrated in a
      murine model of systemic Candida albicans infection with a significant fungal
      load reduction in kidneys. 

PMID- 25585717
TI  - Tunnelling current recognition through core-satellite gold nanoparticles for
      ultrasensitive detection of copper ions.
AB  - We report a new method for ultrasensitive detection of Cu(2+), which is based on
      changes in the tunnelling recognition current across self-assembled core
      satellite gold nanoparticles (GNPs) networks functionalised with amino acids (l
      cysteine). The addition of copper ions induces the formation of GNP/l
      cysteine/Cu(2+)/l-cysteine/GNP molecular junctions and generates a significant
      decrease in the resistance through the networks. The networks are ultrasensitive
      to over ten orders range of copper ion concentrations. 

PMID- 25585719
TI  - Hinchingbrooke staff deserve an apology.
AB  - Imagine being a nurse at Hinchingbrooke Hospital in Cambridgeshire. Those who
      have been there for a while will have endured year after year of mismanagement as
      one regime after another failed to run the trust effectively. First the finances
      were allowed to get into an unholy mess, so the organisation was handed to
      private firm Circle to sort out. Last week, Circle decided to walk away, leaving
      the NHS to start again. 

PMID- 25585718
TI  - Engineering controllable architecture in matrigel for 3D cell alignment.
AB  - We report a microfluidic approach to impart alignment in ECM components in 3D
      hydrogels by continuously applying fluid flow across the bulk gel during the
      gelation process. The microfluidic device where each channel can be independently
      filled was tilted at 90 degrees  to generate continuous flow across the Matrigel
      as it gelled. The presence of flow helped that more than 70% of ECM components
      were oriented along the direction of flow, compared with randomly cross-linked
      Matrigel. Following the oriented ECM components, primary rat cortical neurons and
      mouse neural stem cells showed oriented outgrowth of neuronal processes within
      the 3D Matrigel matrix. 

PMID- 25585720
TI  - A&E departments reach crisis point as trusts buckle under the pressure.
AB  - Thousands of nurses in England are struggling to cope with unprecedented
      pressures on A&E departments, as waiting times reached their worst levels for a
      decade. 

PMID- 25585721
TI  - Government says 'archaic' nursing pay system is barrier to seven-day services.
AB  - The government has launched its strongest attack yet on nurse pay by calling for
      unsocial hours pay to be scrapped. 

PMID- 25585722
TI  - Manifesto addresses 'fundamentals' of healthcare crisis.
AB  - Nurse leaders are rallying MPs to support of a new manifesto for safe staffing
      that sets out the case for increasing the number of registered nurses. 

PMID- 25585723
TI  - Hunt announces more robust checks for Ebola.
AB  - Healthcare workers who have cared for Ebola patients in west Africa may now be
      referred to an infectious diseases specialist if they feel ill when returning to
      the UK, as part of strengthened screening for the virus. 

PMID- 25585724
TI  - Future for hospital staff uncertain as private firm pulls plug on contract.
AB  - Nurses employed at the first NHS hospital to be taken over by a private company
      have been thrown into turmoil after the company decided to pull out of a ten-year
      contract after only two years. 

PMID- 25585725
TI  - New self-funded nursing course aims to address recruitment shortfall.
AB  - A university in the north west of England is offering the first nursing degree
      places that have not been commissioned centrally by Health Education England
      (HEE). 

PMID- 25585727
TI  - L2.5m for specialist nurses in Scotland.
AB  - An online campaign has helped secure an additional L2.5 million for specialist
      nurses in Scotland and double the number of nurses caring for patients with motor
      neurone disease. 

PMID- 25585728
TI  - Night-shift work linked to diabetes risk in black women.
AB  - A major study of black women's health carried out in the United States has found
      those who work night shifts have a greater risk of developing diabetes than those
      who do not. 

PMID- 25585729
TI  - Government introduces action plan to reduce deaths from sepsis.
AB  - Tackling sepsis - the potentially fatal over-reaction of the immune system to
      infection - must be given the same priority as reducing Clostridium difficile and
      MRSA infections, the government has said. 

PMID- 25585730
TI  - Yoga helps residents sleep easy.
AB  - Yoga has been introduced at a care home to help residents sleep better and
      improve their posture and mobility. 

PMID- 25585733
TI  - RCN calls on Home Office to lift barriers to foreign nurses.
AB  - The category of adult nurses should be added to the Home Office Shortage
      Occupation List to allow more clinicians from outside the European Union to work
      in the UK, said the RCN. 

PMID- 25585734
TI  - Dragons breathe life into organ campaign.
AB  - A specialist nurse based at the Norfolk and Norwich University Hospitals NHS
      Foundation Trust will be collaborating on an art project to promote organ
      donation among members of the public. 

PMID- 25585735
TI  - Stonewall names an NHS trust the UK's most LGBT-friendly employer.
AB  - A trust has become the first NHS organisation to be named the best employer for
      gay, lesbian and bisexual people by the charity Stonewall. 

PMID- 25585736
TI  - Invest in nurses to pull NHS out of crisis, alliance urges MPs.
AB  - This week the Safe Staffing Alliance launches a campaign to persuade politicians
      that nurse staffing levels are the key to solving many NHS problems. 

PMID- 25585742
TI  - Smoking cessation.
AB  - Essential facts There are about ten million smokers in the UK. Smoking is the
      country's main cause of preventable illness and premature death, killing more
      than 100,000 people a year. According to ASH: Action on Smoking and Health, two
      thirds of smokers would like to stop. 

PMID- 25585743
TI  - Proud to work here.
AB  - Colchester Hospital has been subjected to a run of negative publicity, most
      recently with regard to its A&E department. Front line and senior nursing staff
      explain that the issues at Colchester are far from unique, with staff facing
      relentless pressure from rising demand.

PMID- 25585744
TI  - 'We are in control'.
AB  - Under the Buurtzorg approach to district nursing in the Netherlands, self-managed
      nurses provide social care as well as nursing care. The result is continuity of
      care and a more rewarding role for nurses who are closely involved with their
      clients.

PMID- 25585745
TI  - The right to try.
AB  - Many clinical commissioning groups have ignored 2013 national guidelines
      requiring them to make IVF available. NICE has recently issued a quality standard
      to tackle this postcode lottery. Nurses can help by alerting local decision
      makers to the human and fi nancial cost of infertility.

PMID- 25585757
TI  - #ISurvivedEbola app.
AB  - People who have recovered from Ebola virus disease in the three west African
      countries worst hit by the outbreak are sharing stories through a mobile app
      launched earlier this month, in a Unicef-backed campaign to inform and fight
      stigma. 

PMID- 25585758
TI  - Losing sight of compassion can lead to patients being starved.
AB  - In 'The best nurse I can be' (Careers January 7), staff nurse Allison Brogan
      reflects on what she learned as a student on Edinburgh Napier University's
      Leadership in Compassionate Care programme. 

PMID- 25585759
TI  - Join the campaign to defend our NHS and a fightback in the Wirral.
AB  - It won't have escaped many people's notice that a general election campaign has
      started and that the NHS, its funding and direction are top of the political
      agenda. 

PMID- 25585763
TI  - Are nurses abusing the use of psychotropic PRN medication?
AB  - The administration of PRN (pro re nata) medication - 'as needed' or 'as the
      situation arises' - is a relatively autonomous component of the nurse's role,
      particularly in mental health units. 

PMID- 25585764
TI  - Competition is key when it comes to fast-food outlets.
AB  - When University Hospital Southampton NHS Foundation Trust announced that it was
      ending its contract with Burger King and not renewing the fast-food outlet's
      concession at the city's general hospital, patients launched a campaign against
      the closure (News January 7). 

PMID- 25585766
TI  - Customer care in the NHS.
AB  - Viewing individuals in need of NHS care as customers has the potential to refocus
      the way their care is delivered. This article highlights some of the benefits of
      reframing the nurse-patient relationship in terms of customer care, and draws
      parallels between good customer care and the provision of high quality patient
      care in the NHS. It explores lessons to be learned from those who have studied
      the customer experience, which can be adapted to enhance the customer care
      experience within the health service. Developing professional expertise in the
      knowledge and skills that underpin good-quality interpersonal encounters is
      essential to improve the customer experience in health care and should be
      prioritised alongside the development of more technical skills. Creating a
      culture where emotional intelligence, caring and compassion are essential
      requirements for all nursing staff will improve patient satisfaction. 

PMID- 25585767
TI  - Reducing urinary tract infections in catheterised patients.
AB  - Urinary tract infections in catheterised patients continue to present a challenge
      in reducing healthcare-associated infection. In this article, an infection
      prevention and control team in one NHS trust reports on using audit results to
      focus attention on measures to reduce bacterial infections. Educational
      initiatives have an important role in reducing infection, but there is no single
      solution to the problem. Practice can be improved using a multi-targeted
      approach, peer review and clinical audit to allow for shared learning and
      experiences. These, along with informal education in the clinical area and more
      formal classroom lectures, can ultimately lead to improved patient outcomes. 

PMID- 25585768
TI  - Reducing medication errors in nursing practice.
AB  - Medication errors remain one of the most common causes of unintended harm to
      patients. They contribute to adverse events that compromise patient safety and
      result in a large financial burden to the health service. The prevention of
      medication errors, which can happen at every stage of the medication preparation
      and distribution process, is essential to maintain a safe healthcare system. One
      third of the errors that harm patients occur during the nurse administration
      phase: administering medication to patients is therefore a high-risk activity.
      This article highlights factors that contribute to medication errors, including
      the safety culture of institutions. It also discusses factors that relate
      specifically to nurses, such as patient acuity and nursing workload, the
      distractions and interruptions that can occur during medication administration,
      the complexity of some medication calculations and administration methods, and
      the failure of nurses to adhere to policies or guidelines. 

PMID- 25585769
TI  - Compassionate care.
AB  - After reading the CPD article, it is clear that compassionate care is fundamental
      to the nursing role. It engages nurses and service users and improves health
      outcomes physically and emotionally. The importance of compassionate care is
      emphasised on almost a daily basis during pre-registration nursing lectures. 

PMID- 25585770
TI  - Care at the start of life.
AB  - Of all the patient groups nurses encounter, neonates are probably the most
      vulnerable. 

PMID- 25585771
TI  - Disseminating information to stem infection.
AB  - Nurses need to be well informed about the Ebola virus, how it is spread and
      transmitted, how they can protect themselves, and above all, how to put on and
      take off the personal protective equipment. 

PMID- 25585774
TI  - Student life - Shape of the future.
AB  - How can nurses and healthcare assistants be better educated and trained? Lord
      Willis of Knaresborough faces this question as he leads a review commissioned by
      the Nursing and Midwifery Council (NMC) and Health Education England (HEE). 

PMID- 25585775
TI  - The influence of bridge-reduced state levels on the electron transfer within the
      2,7-dinitroanthracene radical anion.
AB  - Optical and EPR spectroscopy show that the 2,7-dinitroanthracene radical anion
      has an (apparent) electronic coupling much higher than either its N,N distance or
      its non-Kekule substitution would suggest. The results can only be explained if a
      low-lying bridge redox state is influencing the electron transfer. 

PMID- 25585776
TI  - Introducing prospective manuscript review to address publication bias.

PMID- 25585777
TI  - The evolution of proton beam therapy: insights from early trials and
      tribulations.

PMID- 25585778
TI  - Topical agents for radiation dermatitis in breast cancer: 50 shades of red or
      same old, same old?

PMID- 25585779
TI  - Mometasone furoate cream reduces acute radiation dermatitis in patients receiving
      breast radiation therapy: results of a randomized trial.
AB  - PURPOSE: We wanted to confirm the benefit of mometasone furoate (MF) in
      preventing acute radiation reactions, as shown in a previous study (Bostrom et
      al, Radiother Oncol 2001;59:257-265). METHODS AND MATERIALS: The study was a
      double-blind comparison of MF with D (Diprobase), administered daily from the
      start of radiation therapy for 5 weeks in patients receiving breast radiation
      therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was
      mean modified Radiation Therapy Oncology Group (RTOG) score. RESULTS: Mean RTOG
      scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean
      erythema scores were significantly less for MF than for D (P=.018 and P=.012,
      respectively). The Dermatology Life Quality Index (DLQI) score was significantly
      less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and
      Depression (HAD) questionnaire scores. CONCLUSIONS: MF cream significantly
      reduces radiation dermatitis when applied to the breast during and after
      radiation therapy. For the first time, we have shown a significantly beneficial
      effect on quality of life using a validated instrument (DLQI), for a topical
      steroid cream. We believe that application of this cream should be the standard
      of care where radiation dermatitis is expected.

PMID- 25585780
TI  - Management of the regional lymph nodes following breast-conservation therapy for
      early-stage breast cancer: an evolving paradigm.
AB  - Radiation therapy to the breast following breast conservation surgery has been
      the standard of care since randomized trials demonstrated equivalent survival
      compared to mastectomy and improved local control and survival compared to breast
      conservation surgery alone. Recent controversies regarding adjuvant radiation
      therapy have included the potential role of additional radiation to the regional
      lymph nodes. This review summarizes the evolution of regional nodal management
      focusing on 2 topics: first, the changing paradigm with regard to surgical
      evaluation of the axilla; second, the role for regional lymph node irradiation
      and optimal design of treatment fields. Contemporary data reaffirm prior studies
      showing that complete axillary dissection may not provide additional benefit
      relative to sentinel lymph node biopsy in select patient populations. Preliminary
      data also suggest that directed nodal radiation therapy to the supraclavicular
      and internal mammary lymph nodes may prove beneficial; publication of several
      studies are awaited to confirm these results and to help define subgroups with
      the greatest likelihood of benefit. 

PMID- 25585782
TI  - Are we appropriately selecting therapy for patients with cervical cancer?
      Longitudinal patterns-of-care analysis for stage IB-IIB cervical cancer.
AB  - PURPOSE: We performed a patterns-of-care analysis evaluating the effects of newer
      technology and recent research findings on treatment decisions over 26 years to
      determine whether patients with cervical cancer are being appropriately selected
      for treatment to optimize the therapeutic ratio. METHODS AND MATERIALS: A
      retrospective analysis was conducted using the Surveillance, Epidemiology and End
      Results (SEER) program from 1983 to 2009. We identified 10,933 women with stage
      IB-IIB cervical carcinoma. RESULTS: Of the 10,933 subjects identified, 40.1%
      received surgery, 26.8% received radiation (RT), and 33.1% received surgery plus
      RT. RT use increased after 2000 compared to prior to 2000, with a corresponding
      decrease in surgery and surgery plus RT. Among patients with risk factors
      including tumor size >4 cm, positive parametria, and positive lymph nodes,
      declining use of surgery plus RT was observed. However, 23% of patients with
      tumors >4 cm, 20% of patients with positive parametria, and 55% of node-positive
      patients continued to receive surgery plus RT as of 2009. Factors associated with
      increased use of surgery plus RT included patient age <50 and node-positive
      status. CONCLUSIONS: In this largest patterns-of-care analysis to date for
      patients with locally advanced cervical cancer, we found a substantial proportion
      of patients continue to undergo surgery followed by radiation, despite randomized
      data supporting the use of definitive radiation therapy, with lower morbidity
      than surgery and radiation.

PMID- 25585781
TI  - Chemoradiation with concomitant boosts followed by radical surgery in locally
      advanced cervical cancer: long-term results of the ROMA-2 prospective phase 2
      study.
AB  - PURPOSE: This prospective, phase 2 study aimed at assessing the efficacy of
      accelerated fractionation radiation therapy by concomitant boosts (CBs)
      associated with chemoradiation therapy (CRT) of the whole pelvis, in improving
      the rate of pathological complete response (pCR) to treatment in patients with
      International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA
      locally advanced cervical cancer. METHODS AND MATERIALS: Neoadjuvant CRT included
      conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8
      cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and
      parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions,
      every other day). Concomitant chemotherapy included cisplatin (20 mg/m(2), days 1
      4 and 26-30 of treatment), and capecitabine (1300 mg/m(2)/daily, orally) during
      the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic
      with or without aortic lymphadenectomy was performed within 6 to 8 weeks from
      CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity
      criteria and Chassagne grading system. Based on the Simon design, 103 cases were
      required, and the regimen would be considered active if >45 pCR were registered
      (alpha error = 0.05; beta error = 0.1). RESULTS: pCR was documented in 51 cases
      (50.5%), and the regimen was considered active, according to the planned
      statistical assumptions. At median follow-up of 36 months (range: 7-85 months),
      the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall
      survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and
      neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal
      toxicity was always grade 1 or 2. CONCLUSIONS: Addition of CBs in the accelerated
      fractionation modality to the whole pelvis chemoradiation followed by radical
      surgery results in a high rate of pathologically assessed complete response to
      CRT and a very encouraging local control rate, with acceptable toxicity.

PMID- 25585783
TI  - Stereotactic ablative radiation therapy for subcentimeter lung tumors: clinical,
      dosimetric, and image guidance considerations.
AB  - PURPOSE: Use of stereotactic ablative radiation therapy (SABR) for subcentimeter
      lung tumors is controversial. We report our outcomes for tumors with diameter <=1
      cm and their visibility on cone beam computed tomography (CBCT) scans and
      retrospectively evaluate the planned dose using a deterministic dose calculation
      algorithm (Acuros XB [AXB]). METHODS AND MATERIALS: We identified subcentimeter
      tumors from our institutional SABR database. Tumor size was remeasured on an
      artifact-free phase of the planning 4-dimensional (4D)-CT. Clinical plan doses
      were generated using either a pencil beam convolution or an anisotropic analytic
      algorithm (AAA). All AAA plans were recalculated using AXB, and differences among
      D95 and mean dose for internal target volume (ITV) and planning target volume
      (PTV) on the average intensity CT dataset, as well as for gross tumor volume
      (GTV) on the end respiratory phases were reported. For all AAA patients, CBCT
      scans acquired during each treatment fraction were evaluated for target
      visibility. Progression-free and overall survival rates were calculated using the
      Kaplan-Meier method. RESULTS: Thirty-five patients with 37 subcentimeter tumors
      were eligible for analysis. For the 22 AAA plans recalculated using AXB, Mean D95
      +/- SD values were 2.2 +/- 4.4% (ITV) and 2.5 +/- 4.8% (PTV) lower using AXB;
      whereas mean doses were 2.9 +/- 4.9% (ITV) and 3.7 +/- 5.1% (PTV) lower.
      Calculated AXB doses were significantly lower in one patient (difference in mean
      ITV and PTV doses, as well as in mean ITV and PTV D95 ranged from 22%-24%).
      However, the end respiratory phase GTV received at least 95% of the prescription
      dose. Review of 92 CBCT scans from all AAA patients revealed that the tumor was
      visualized in 82 images, and its position could be inferred in other images. The
      2-year local progression-free survival was 100%. CONCLUSIONS: Patients with
      subcentimeter lung tumors are good candidates for SABR, given the dosimetry,
      ability to localize tumors with image guidance, and excellent local control.

PMID- 25585784
TI  - The impact of adjuvant radiation therapy for high-grade gliomas by histology in
      the United States population.
AB  - PURPOSE: To compare the survival impact of adjuvant external beam radiation
      therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma
      (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma
      (AOA) histology. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End
      Results (SEER) database was queried from 1998 to 2007 for patients aged >=18
      years with high-grade gliomas managed with upfront surgical resection, treated
      with and without adjuvant RT. RESULTS: The primary analysis totaled 14,461
      patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and
      316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with
      significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%,
      p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%,
      p=.026). No significant differences in OS were observed for AOs (5-year OS, with
      RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards
      models accounting for extent of resection, age, sex, race, year, marital status,
      and tumor registry, RT was associated with significantly improved OS for both
      GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68;
      P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45
      1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions
      were not performed for AOs. A significant interaction was observed between the
      survival impact of RT and histology overall (interaction P<.001) and in a model
      limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024),
      characterizing histology as a significant predictive factor for the impact of RT.
      Subgroup analyses demonstrated greater hazard reductions with RT among patients
      older than median age for both GBMs and AAs (all interaction P<=.001). No
      significant interactions were observed between RT and extent of resection.
      Identical patterns of significance were observed for cause-specific survival and
      OS across analyses. CONCLUSIONS: In this large population-based cohort, glioma
      histology represented a significant predictor for the survival impact of RT.
      Adjuvant RT was associated with improved survival for AAs, with benefits
      comparable to those observed for GBMs over the same 10-year interval. No survival
      advantage was observed with adjuvant RT for AOs.

PMID- 25585785
TI  - Single- versus multifraction stereotactic body radiation therapy for pancreatic
      adenocarcinoma: outcomes and toxicity.
AB  - PURPOSE: We report updated outcomes of single- versus multifraction stereotactic
      body radiation therapy (SBRT) for unresectable pancreatic adenocarcinoma. METHODS
      AND MATERIALS: We included 167 patients with unresectable pancreatic
      adenocarcinoma treated at our institution from 2002 to 2013, with 1-fraction
      (45.5% of patient) or 5-fraction (54.5% of patients) SBRT. The majority of
      patients (87.5%) received chemotherapy. RESULTS: Median follow-up was 7.9 months
      (range: 0.1-63.6). The 6- and 12-month cumulative incidence rates (CIR) of local
      recurrence for patients treated with single-fraction SBRT were 5.3% (95%
      confidence interval [CI], 0.2%-10.4%) and 9.5% (95% CI, 2.7%-16.2%),
      respectively. The 6- and 12-month CIR with multifraction SBRT were 3.4% (95% CI,
      0.0-7.2%) and 11.7% (95% CI, 4.8%-18.6%), respectively. Median survival from
      diagnosis for all patients was 13.6 months (95% CI, 12.2-15.0 months). The 6- and
      12- month survival rates from SBRT for the single-fraction group were 67.0% (95%
      CI, 57.2%-78.5%) and 30.8% (95% CI, 21.9%-43.6%), respectively. The 6- and 12-
      month survival rates for the multifraction group were 75.7% (95% CI, 67.2%-85.3%)
      and 34.9% (95% CI, 26.1%-46.8%), respectively. There were no differences in CIR
      or survival rates between the single- and multifraction groups. The 6- and 12
      month cumulative incidence rates of gastrointestinal toxicity grade >=3 were 8.1%
      (95% CI, 1.8%-14.4%) and 12.3% (95% CI, 4.7%-20.0%), respectively, in the single
      fraction group, and both were 5.6% (95% CI, 0.8%-10.5%) in the multifraction
      group. There were significantly fewer instances of toxicity grade >=2 with
      multifraction SBRT (P=.005). Local recurrence and toxicity grade >=2 were
      independent predictors of worse survival. CONCLUSIONS: Multifraction SBRT for
      pancreatic cancer significantly reduces gastrointestinal toxicity without
      compromising local control.

PMID- 25585787
TI  - Differential motion between mediastinal lymph nodes and primary tumor in
      radically irradiated lung cancer patients.
AB  - PURPOSE/OBJECTIVE: In patients with locally advanced lung cancer, planning target
      volume margins for mediastinal lymph nodes and tumor after a correction protocol
      based on bony anatomy registration typically range from 1 to 1.5 cm. Detailed
      information about lymph node motion variability and differential motion with the
      primary tumor, however, is lacking from large series. In this study, lymph node
      and tumor position variability were analyzed in detail and correlated to the main
      carina to evaluate possible margin reduction. METHODS AND MATERIALS: Small gold
      fiducial markers (0.35 * 5 mm) were placed in the mediastinal lymph nodes of 51
      patients with non-small cell lung cancer during routine diagnostic esophageal or
      bronchial endoscopic ultrasonography. Four-dimensional (4D) planning computed
      tomographic (CT) and daily 4D cone beam (CB) CT scans were acquired before and
      during radical radiation therapy (66 Gy in 24 fractions). Each CBCT was
      registered in 3-dimensions (bony anatomy) and 4D (tumor, marker, and carina) to
      the planning CT scan. Subsequently, systematic and random residual misalignments
      of the time-averaged lymph node and tumor position relative to the bony anatomy
      and carina were determined. Additionally, tumor and lymph node respiratory
      amplitude variability was quantified. Finally, required margins were quantified
      by use of a recipe for dual targets. RESULTS: Relative to the bony anatomy,
      systematic and random errors ranged from 0.16 to 0.32 cm for the markers and from
      0.15 to 0.33 cm for the tumor, but despite similar ranges there was limited
      correlation (0.17-0.71) owing to differential motion. A large variability in
      lymph node amplitude between patients was observed, with an average motion of
      0.56 cm in the cranial-caudal direction. Margins could be reduced by 10% (left
      right), 27% (cranial-caudal), and 10% (anteroposterior) for the lymph nodes and 
      2%, 15%, and 7% for the tumor if an online carina registration protocol replaced
      a protocol based on bony anatomy registration. CONCLUSIONS: Detailed analysis
      revealed considerable lymph node position variability, differential motion, and
      respiratory motion. Planning target volume margins can be reduced up to 27% in
      lung cancer patients when the carina registration replaces bony anatomy
      registration.

PMID- 25585786
TI  - Reciprocal regulation of hypoxia-inducible factor 2alpha and GLI1 expression
      associated with the radioresistance of renal cell carcinoma.
AB  - PURPOSE: Renal cell carcinoma (RCC) is often considered a radioresistant tumor,
      but the molecular mechanism underlying its radioresistance is poorly understood.
      This study explored the roles of hypoxia-inducible factor 2alpha (HIF2alpha) and
      sonic hedgehog (SHH)-GLI1 signaling in mediating the radioresistance of RCC cells
      and to unveil the interaction between these 2 signaling pathways. METHODS AND
      MATERIALS: The activities of SHH-GLI1 signaling pathway under normoxia and
      hypoxia in RCC cells were examined by real-time polymerase chain reaction,
      Western blot, and luciferase reporter assay. The expression of HIF2alpha and GLI1
      in RCC patients was examined by immunohistochemistry, and their correlation was
      analyzed. Furthermore, RCC cells were treated with HIF2alpha-specific shRNA (sh
      HIF2alpha), GLI1 inhibitor GANT61, or a combination to determine the effect of
      ionizing radiation (IR) on RCC cells based on clonogenic assay and double-strand
      break repair assay. RESULTS: RCC cells exhibited elevated SHH-GLI1 activities
      under hypoxia, which was mediated by HIF2alpha. Hypoxia induced GLI1 activation
      through SMO-independent pathways that could be ablated by PI3K inhibitor or MEK
      inhibitor. Remarkably, the SHH-GLI1 pathway also upregulated HIF2alpha expression
      in normoxia. Apparently, there was a positive correlation between HIF2alpha and
      GLI1 expression in RCC patients. The combination of sh-HIF2alpha and GLI1
      inhibitor significantly sensitized RCC cells to IR. CONCLUSIONS: Cross-talk
      between the HIF2alpha and SHH-GLI1 pathways was demonstrated in RCC. Cotargeting
      these 2 pathways, significantly sensitizing RCC cells to IR, provides a novel
      strategy for RCC treatment.

PMID- 25585788
TI  - Perspectives in breast cancer treatment: APBI and breast-conserving surgery. In
      regard to Moran et al and Smith et al.

PMID- 25585789
TI  - Perspectives in breast cancer treatment: APBI and breast-conserving surgery. In
      reply to Morgan and Vaidya.

PMID- 25585790
TI  - Correlation of 18F-FDG PET avid volumes on pre-radiation therapy and post
      radiation therapy FDG PET scans in recurrent lung cancer. In regard to Shusharina
      et al.

PMID- 25585791
TI  - Correlation of 18F-FDG PET avid volumes on pre-radiation therapy and post
      radiation therapy FDG PET scans in recurrent lung cancer. In reply to Saraiya et
      al.

PMID- 25585792
TI  - Radiation therapy infrastructure and human resources in low- and middle-income
      countries: present status and projections for 2020. In regard to Datta et al.

PMID- 25585793
TI  - Radiation therapy infrastructure and human resources in low- and middle-income
      countries: present status and projections for 2020. In reply to Sharma et al.

PMID- 25585794
TI  - Estimating the size of populations at high risk for HIV using respondent-driven
      sampling data.
AB  - The study of hard-to-reach populations presents significant challenges.
      Typically, a sampling frame is not available, and population members are
      difficult to identify or recruit from broader sampling frames. This is especially
      true of populations at high risk for HIV/AIDS. Respondent-driven sampling (RDS)
      is often used in such settings with the primary goal of estimating the prevalence
      of infection. In such populations, the number of people at risk for infection and
      the number of people infected are of fundamental importance. This article
      presents a case-study of the estimation of the size of the hard-to-reach
      population based on data collected through RDS. We study two populations of
      female sex workers and men-who-have-sex-with-men in El Salvador. The approach is
      Bayesian and we consider different forms of prior information, including using
      the UNAIDS population size guidelines for this region. We show that the method is
      able to quantify the amount of information on population size available in RDS
      samples. As separate validation, we compare our results to those estimated by
      extrapolating from a capture-recapture study of El Salvadorian cities. The
      results of our case-study are largely comparable to those of the capture
      recapture study when they differ from the UNAIDS guidelines. Our method is widely
      applicable to data from RDS studies and we provide a software package to
      facilitate this. 

PMID- 25585795
TI  - Rac1 is correlated with aggressiveness and a potential therapeutic target for
      gastric cancer.
AB  - Rac1 is a member of the Rho GTPase family. Rac1 activity is critical in
      regulating cytoskeleton organization and thus, modulates a diverse spectrum of
      cellular functions in normal and malignant cells. The aims of the present study
      were to investigate the expression pattern and clinical significance of Rac1, as
      well as the role of Rac1 in gastric cancer tumorigenesis and metastasis. The
      expression of Rac1 in human gastric cancer was explored by immunohistochemistry.
      The correlation of Rac1 expression with the clinicopathological characteristics
      and the survival of patients were analyzed by Pearson's Chi-square and Kaplan
      Meier analyses, respectively. Rac1 overexpression cell model was used to examine
      in vitro and in vivo effects of Rac1 in cell growth, migration and invasion. Rac1
      was highly expressed in gastric cancer tissues and correlated with
      differentiation, local invasion, lymph node metastasis and Lauren's
      classification. Rac1 expression in gastric cancer predicted shorter survival.
      Overexpression of Rac1 in gastric cancer cells dramatically induced Rac1
      activation and rendered a more aggressive phenotype such as increased cell growth
      and migration/invasion in vitro and in vivo. Inhibiting Rac1 activity by specific
      inhibitor abrogated the effects of Rac1 on the malignant phenotype. Our clinical
      findings demonstrated that Rac1 was well correlated with aggressiveness and a
      negative prognostic factor. In addition, our data on experimental cell models
      supported the fundamental role of Rac1 in gastric cancer. Given its pivotal role
      in gastric tumorigenesis and progression, Rac1 can serve as a promising
      therapeutic target for gastric cancer.

PMID- 25585797
TI  - [Erratum to: Do intraocular pressure measurements over 48 h make sense?].

PMID- 25585796
TI  - [Prevalence of glaucoma in obstructive sleep apnea].
AB  - BACKGROUND: A causal relationship between glaucoma and obstructive sleep apnea
      has been postulated in several clinical studies but also refuted by others. The
      aim of this study was to determine the prevalence of glaucoma in a cohort of
      patients with well-established obstructive sleep apnea in comparison to the
      published data on this topic. METHODS: A total of 100 consecutive patients
      (male:female  80:20, mean age 59 +/- 11 years SD) with polysomnographically
      established obstructive sleep apnea underwent an ophthalmological examination
      including tonometry, static perimetry and dilated fundus photography. Visual
      fields and fundus photographs of the patients were classified as glaucomatous or
      non-glaucomatous by two independent examiners. RESULTS: The prevalence of
      glaucoma in the study patients was 2 % which corresponded to the published
      prevalence of glaucoma in the normal population. Intraocular pressure did not
      correlate with the respiratory index, body mass index or sex. CONCLUSION: The
      data from this study shed doubt on a causal relationship between obstructive
      sleep apnea and glaucoma.

PMID- 25585798
TI  - Essentials in the life process indicated by the self-referential genetic code.
AB  - The self-referential genetic encoding starts with glycine and serine, in the
      realm of one-carbon units of metabolism. It is proposed that the prototRNA dimer
      directed mechanism of protein synthesis and encoding promotes a sink dynamics
      that corresponds to the driving 'force' for the fixation of the supporting
      metabolic pathways. A succession of processes is delineated, ending up in
      reproduction, which accomplished the function of reinforcing the protein
      synthesis metabolic sink mechanism. 

PMID- 25585799
TI  - The power of crowding for the origins of life.
AB  - Molecular crowding increases the likelihood that life as we know it would emerge.
      In confined spaces, diffusion distances are shorter, and chemical reactions
      produce fewer and more regular products. Crowding will occur in the spaces
      between Muscovite mica sheets, which has many advantages as a site for life's
      origins. 

PMID- 25585800
TI  - Protein ordered sequences are formed by random joining of amino acids in protein
      0(th)-order structure, followed by evolutionary process.
AB  - Only random processes should occur on the primitive Earth. In contrast, many
      ordered sequences are synthesized according to genetic information on the present
      Earth. In this communication, I have proposed an idea that protein 0(th)-order
      structures or specific amino acid compositions would mediate the transfer from
      random process to formation of ordered sequences, after formation of double
      stranded genes. 

PMID- 25585801
TI  - The minimal autopoietic unit.
AB  - It is argued that closed, cell-like compartments, may have existed in prebiotic
      time, showing a simplified metabolism which was bringing about a primitive form
      of stationary state- a kind of homeostasis. The autopoietic primitive cell can be
      taken as an example and there are preliminary experimental data supporting the
      possible existence of this primitive form of cell activity. The genetic code
      permits, among other things, the continuous self-reproduction of proteins;
      enzymic proteins permit the synthesis of nucleic acids, and in this way there is
      a perfect recycling between the two most important classes of biopolymers in our
      life. On the other hand, the genetic code is a complex machinery, which cannot be
      posed at the very early time of the origin of life. And the question then arises,
      whether some form of alternative beginning, prior to the genetic code, would have
      been possible: and this is the core of the question asked. Is something with the
      flavor of early life conceivable, prior to the genetic code? My answer is
      positive, although I am too well aware that the term "conceivable" does not mean
      that this something is easily to be performed experimentally. To illustrate my
      answer, I would first go back to the operational description of cellular life as
      given by the theory of autopoiesis. Accordingly, a living cell is an open system
      capable of self-maintenance, due to a process of internal self-regeneration of
      the components, all within a boundary which is itself product from within. This
      is a universal code, valid not only for a cell, but for any living macroscopic
      entity, as no living system exists on Earth which does not obey this principle.
      In this definition (or better operational description) there is no mention of DNA
      or genetic code. I added in that definition the term "open system"-which is not
      present in the primary literature (Varela, et al., 1974) to make clear that every
      living system is indeed an open system-without this addition, it may seem that
      with autopoiesis we are dealing with a perpetuum mobile, against the second
      principle of thermodynamics. Now consider the following figure (Fig. 1). It
      represents in a very schematic form a cell, as an open system, with a
      semipermeable membrane constituted by the chemical S, which permits the entrance
      of the nutrient A and the elimination of the decay product P. A is transformed
      inside the cell into S by a chemical reaction characterized by kgen, and S can be
      transformed into P by the reaction kdec. The two reactions actually may represent
      two entire families of reaction, in the sense that one can envisage several A and
      several S and several P.

PMID- 25585803
TI  - Open Questions on the Origin of Life (OQOL)--introduction to the special issue.

PMID- 25585802
TI  - Cell-free synthesis of SecYEG translocon as the fundamental protein transport
      machinery.
AB  - The cell membrane has many indispensable functions for sustaining cell alive
      besides a role as merely outer envelope. The most of such functions are
      implemented by membrane embedded proteins that are emerged through the membrane
      integration machinery, SecYEG translocon. Here, we synthesized SecYEG by
      expressing the corresponding gene in vitro to study the process of
      functionalization of the cell membrane. 

PMID- 25585804
TI  - Molecular crowding and early evolution.
AB  - The environment of protocells might have been crowded with small molecules and
      functional and non-specific polymers. In addition to altering conformational
      equilibria, affecting reaction rates and changing the structure and activity of
      water, crowding might have enhanced the capabilities of protocells for
      evolutionary innovation through the creation of extended neutral networks in the
      fitness landscape. 

PMID- 25585805
TI  - Two perspectives on the origin of the standard genetic code.
AB  - The origin of a genetic code made it possible to create ordered sequences of
      amino acids. In this article we provide two perspectives on code origin by
      carrying out simulations of code-sequence coevolution in finite populations with
      the aim of examining how the standard genetic code may have evolved from more
      primitive code(s) encoding a small number of amino acids. We determine the
      efficacy of the physico-chemical hypothesis of code origin in the absence and
      presence of horizontal gene transfer (HGT) by allowing a diverse collection of
      code-sequence sets to compete with each other. We find that in the absence of
      horizontal gene transfer, natural selection between competing codes distinguished
      by differences in the degree of physico-chemical optimization is unable to
      explain the structure of the standard genetic code. However, for certain
      probabilities of the horizontal transfer events, a universal code emerges having
      a structure that is consistent with the standard genetic code. 

PMID- 25585806
TI  - Specific transformation of assembly with actin filaments and molecular motors in
      a cell-sized self-emerged liposome.
AB  - Eukaryotes, by the same combination of cytoskeleton and molecular motor, for
      example actin filament and myosin, can generate a variety of movements. For this
      diversity, the organization of biological machineries caused by the confinement
      and/or crowding effects of internal living cells, may play very important roles. 

PMID- 25585807
TI  - Spontaneous mutual ordering of nucleic acids and proteins.
AB  - It is proposed that the prebiotic ordering of nucleic acid and peptide sequences
      was a cooperative process in which nearly random populations of both kinds of
      polymers went through a codependent series of self-organisation events that
      simultaneously refined not only the accuracy of genetic replication and coding
      but also the functional specificity of protein catalysts, especially nascent
      aminoacyl-tRNA synthetase "urzymes". 

PMID- 25585808
TI  - UN cannot be sued for alleged role in Haitian cholera outbreak, US judge rules.

PMID- 25585809
TI  - Using Young Mothers' Clubs to Improve Knowledge of Postpartum Hemorrhage and
      Family Planning in Informal Settlements in Nairobi, Kenya.
AB  - Women living in Nairobi's informal settlements face a higher risk of maternal
      death than those living elsewhere in the country, and have limited knowledge of
      actions they can take to improve their chances of survival during pregnancy and
      childbirth. As one strategy to reach this high risk group, Jhpiego has
      implemented young mothers' clubs (YMCs). These clubs comprise mothers aged 18-30
      who come together on a weekly basis to share experiences and solutions to their
      challenges while receiving health education from health facility staff and
      community health workers (CHWs). The aim of this study was to assess whether the
      YMC strategy could be used to improve participants' knowledge of postpartum
      hemorrhage (PPH), positive behavior around childbirth, and family planning.
      Participants in nine YMCs (n = 193) across four informal settlements were
      interviewed to assess their knowledge of safe motherhood topics before and after
      a series of eight health education sessions. Data were analyzed with the McNemar
      test to determine significance of change in knowledge pre- and post-intervention.
      The largest improvements were observed in knowledge about what to include in a
      birth plan, with correct responses increasing from 32 to 73% (p < 0.001), 58-93%
      (p < 0.001), 36-66% (p < 0.001), 58-85% (p < 0.001), and 64-88% (p < 0.001) for
      identifying a birth companion, budget, skilled birth attendant, emergency
      supplies, and place of birth, respectively. Less substantial improvements were
      observed in knowledge of danger signs of PPH (up 10% from 77%, p = 0.003).
      Although knowledge of actions to take in the event of bleeding after delivery did
      significantly improve, final knowledge scores remained low--knowledge to urinate
      increased from 14 to 28% (p < 0.001) and to breastfeed from 12 to 24% (p =
      0.005). Even though the vast majority of respondents (84%) knew before the
      intervention that a woman should space pregnancy by at least 2 years after
      delivery, there was an increase to 94% after the sessions (p = 0.008). Overall,
      participants demonstrated significant improvements in knowledge of safe
      motherhood and family planning topics, suggesting that the materials and methods
      used were generally effective for improving knowledge among this high risk group.

PMID- 25585810
TI  - Dimensions of the trapezium bone: a cadaver and CT study.
AB  - PURPOSE: The primary purpose of this study was to define the size of the
      trapezium bone through measurements on cadaver specimens and CT scans of living
      subjects. The secondary purpose of this study was to determine if any correlation
      existed between the size of the trapezium and local anatomical parameters.
      METHODS: The radio-ulnar length (L), dorsopalmar width (l) and height (h) of the
      distal surface of the trapezium were measured by two independent observers on 20
      cadaver specimens. The same measurements were carried out by two other observers
      on anonymized CT scans from 18 patients. The inter- and intra-observer agreement
      was determined using the intraclass correlation coefficient. RESULTS: In the
      cadavers, the mean length, width and height of the trapezium were 22.8, 15.5 and
      15.2 mm, respectively. On the CT scans, these same dimensions were 19.2, 11.4 and
      11.6 mm. Inter-observer agreement was statistically significant in both parts of
      the study. DISCUSSION: The dimensions of the trapezium bone were about 3.33 mm
      larger in cadavers than on CT scans. These differences can be explained partially
      by a systematic under-sizing error on the CT scans and the fact that the
      cartilage layer cannot be directly visualized. CONCLUSION: This study was able to
      define the dimensions of the trapezium bone. It may be possible to predict the
      trapezium height from the length of the forearm or the width of the radial
      epiphysis. Our data can be used to adjust the size of trapezium implants to the
      dimensions of the patient's bone.

PMID- 25585811
TI  - Blending of the lateral deep slip of the platysma muscle into the buccinator
      muscle.
AB  - PURPOSE: The aim of this study was to clarify the prevalence of blending of the
      lateral deep slip of the platysma into the buccinator, and the morphologic and
      spatial relationships thereof. METHODS: The lateral deep slip of the platysma was
      investigated in 42 specimens of embalmed adult Korean cadavers. RESULTS: The
      lateral deep slip of the platysma was observed in 17 of the 42 specimens (40.5
      %). When present, it divided from the deep portion (16 specimens, 38.1 %) or the
      lateral portion (1 specimen, 2.4 %) of the platysma pars modiolaris. The lateral
      deep slip passed deep to the facial artery, where it blended into the inferior
      part of the buccinator. The blending site was located inferolateral to the
      modiolus. After blending into the buccinator, the fibers of the lateral deep slip
      coursed longitudinally with the inferior fibers of the buccinator. CONCLUSION:
      The present description of the topography of the lateral deep slip of the
      platysma and its relationship with surrounding structures could improve the
      understanding of the detailed movements of the lower face and the related EMG
      activities, with the data also being useful when performing facial surgery.

PMID- 25585812
TI  - Comparison between performances of three types of manual wheelchairs often
      distributed in low-resource settings.
AB  - PURPOSE: This study was conducted to compare the performance of three types of
      chairs in a low-resource setting. The larger goal was to provide information
      which will enable more effective use of limited funds by wheelchair manufacturers
      and suppliers in low-resource settings. METHODS: The Motivation Rough Terrain and
      Whirlwind Rough Rider were compared in six skills tests which participants
      completed in one wheelchair type and then a day later in the other. A hospital
      style folding transport wheelchair was also included in one test. For all skills,
      participants rated the ease or difficulty on a visual analogue scale. For all
      tracks, distance traveled and the physiological cost index were recorded. Data
      were analyzed using repeated measures analysis of variance. RESULTS: The
      Motivation wheelchair outperformed Whirlwind wheelchair on rough and smooth
      tracks, and in some metrics on the tight spaces track. Motivation and Whirlwind
      wheelchairs significantly outperformed the hospital transport wheelchair in all
      metrics on the rough track skills test. CONCLUSION: This comparative study
      provides data that are valuable for manufacturers and for those who provide
      wheelchairs to users. The comparison with the hospital-style transport chair
      confirms the cost to users of inappropriate wheelchair provision. Implications
      for Rehabilitation For those with compromised lower limb function, wheelchairs
      are essential to enable full participation and improved quality of life.
      Therefore, provision of wheelchairs which effectively enable mobility in the
      cultures and environments in which people with disabilities live is crucial. This
      includes low-resource settings where the need for appropriate seating is
      especially urgent. A repeated measures study to measure wheelchair performances
      in everyday skills in the setting where wheelchairs are used gives information on
      the quality of mobility provided by those wheelchairs. This study highlights
      differences in the performance of three types of wheelchairs often distributed in
      low-resource settings. This information can improve mobility for wheelchair users
      in those settings by enabling wheelchair manufacturers to optimize wheelchair
      design and providers to optimize the use of limited funds.

PMID- 25585813
TI  - Everyday use of assistive technology devices in school settings.
AB  - PURPOSE: To gain more knowledge about ATDs as social-cultural objects in school
      settings, particularly from the children's perspective. METHODS: Nine children
      with cerebral palsy, aged five to six years, were observed 3 days in kindergarten
      and twice in the first year at primary school. At the primary school, we
      interviewed the children. During the interviews, the children were shown photos
      taken during the observations. In addition, dialogues with parents, therapists
      and school staff were carried out. RESULTS AND DISCUSSIONS: ATDs seem to have the
      potential both to exacerbate disability and to enhance selfhood, embodied
      capacities and participation. Through use, ATDs become social objects with
      symbolic values that influence their use. Devices corporally embedded into the
      child's body schema appeared as facilitators for participation in culturally
      valued activities. In contrast, devices prescribed as medical interventions
      tended to be greeted with ambivalence by the children themselves, their parents
      and school staff. A device incorporated into one situation was not necessarily
      relevant for use in another. CONCLUSIONS: In recognizing the value of exploring
      children's experiences, professionals are left with the challenge of creating
      space for children to reflect on the worthiness of an ATD across place, time and
      functionality. Implications for Rehabilitation Used in everyday life, ATDs become
      social objects with potential both to exacerbate disability and to enhance
      selfhood, embodied capacities and participation. The child's everyday environment
      is a vulnerable setting for implementing rehabilitation interventions, such as
      ATDs. Creating space for children to reflect on the worthiness of an ATD,
      regarding place, time and functionality, may enhance their participation in
      everyday life.

PMID- 25585814
TI  - Minocycline alleviates sevoflurane-induced cognitive impairment in aged rats.
AB  - Minocycline has been implicated in the treatment for multiple diseases in the
      nervous system for its neuroprotective properties. However, the mechanism by
      which minocycline benefits postoperative anesthesia-induced cognitive dysfunction
      is still unclear. In this study, we introduced minocycline to a rat model of
      anesthetic-induced learning and memory impairment, to investigate the effects of
      minocycline on neuroinflammation, beta amyloid (Abeta) deposition, and activation
      of nuclear factor kappaB (NF-kappaB) signaling pathway in the hippocampus. Aged
      rats were treated with sevoflurane to induce cognitive impairment with and
      without pre-administration of minocycline. The rats were then subjected to Morris
      water maze tests to evaluate their learning and memory performance. Subsequently,
      apoptosis in the hippocampal tissue was assessed with TUNEL assays. Furthermore,
      the levels of apoptosis-related proteins and pro-inflammatory cytokines, Abeta
      responses, and activation of the NF-kappaB signaling pathway in the hippocampus
      were examined by Western blot analysis. Our results revealed that minocycline
      effectively alleviated sevoflurane-induced cognitive impairment in aged rats.
      Minocycline reduced sevoflurane-induced neuronal apoptosis and inflammation, as
      well as suppressed sevoflurane-induced Abeta accumulation and activation of NF
      kappaB signaling pathway in the hippocampus of aged rats. In conclusion, our
      findings indicate that minocycline is a potent agent to counteract sevoflurane
      induced cognitive impairment and neurotoxicity in the nervous system of aged
      rats, which is likely to be mediated via NF-kappaB signaling pathway.

PMID- 25585816
TI  - Effects of two different waveforms of ELF MF on bioelectrical activity of
      antennal lobe neurons of Morimus funereus (Insecta, Coleoptera).
AB  - PURPOSE: External magnetic fields (MF) interact with organisms at all levels,
      including the nervous system. Bioelectrical activity of antennal lobe neurons of
      adult Morimus funereus was analyzed under the influence of extremely low
      frequency MF (ELF MF, 50 Hz, 2 mT) of different characteristics (exposure
      duration and waveform). MATERIAL AND METHODS: Neuronal activity
      (background/neuronal population and those nearest to the recording electrode) in
      adult longhorn beetles was registered through several phases of exposure to the
      sine wave and square wave MF for 5, 10 and 15 min. RESULTS: The sine wave MF,
      regardless of the exposure duration, did not change the reversibility factor of
      antennal lobe neuronal activity in adult M. funereus. In contrast, reversibility
      factors of the nearest neurons were significantly changed after the exposure to
      square wave MF for 10 and 15 min. CONCLUSION: M. funereus individuals are
      sensitive to both sine wave and square wave ELF MF (50 Hz, 2 mT) of different
      duration, whereby their reactions depend on the characteristics of the applied MF
      and specificity of each individual.

PMID- 25585815
TI  - The ATM inhibitor KU55933 sensitizes radioresistant bladder cancer cells with
      DAB2IP gene defect.
AB  - PURPOSE: Our preliminary results showed that differentially expressed in ovarian
      cancer-2/disabled homolog 2 (DOC-2/DAB2) interactive protein (DAB2IP), a putative
      tumor suppressor gene, is down-regulated in bladder cancer (BCa) with aggressive
      phenotypes. In this study, we investigated how DAB2IP knockdown influenced BCa
      cell response to ionizing radiation (IR) and discussed possible ways to enhance
      cell radiosensitivity. METHODS AND MATERIALS: The small interfering RNA (siRNA)
      system was implemented to inhibit endogenous DAB2IP expression in two human BCa
      cell lines, T24 and 5637. Cell sensitivity to IR alone or combined treatment was
      measured by a colony formation assay (CFA). Western blot was used to determine
      the phosphorylation levels of ataxia-telangiectasia mutated (ATM), catalytic
      subunit of the DNA-dependent protein kinase (DNA-PKcs) and related DNA damage
      repair (DDR) proteins. Immunofluorescence as well as a flow cytometry assay were
      employed to detect DNA double-strand break (DSB) repair and cell cycle
      distribution, respectively. RESULTS: DAB2IP-knockdown of BCa cells (i.e.,
      siDAB2IP) exhibit increased clonogenic survival in response to IR compared with
      control cells (i.e., siCON) expressing an endogenous level of DAB2IP. The
      mechanism in siDAB2IP cells could be explained by elevated ATM expression and
      activation, increased S phase cell distribution as well as faster DSB repair
      kinetics. 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one (KU55933) significantly
      sensitized siDAB2IP cells to IR due to inhibition of the phosphorylation of ATM
      and its downstream targets following IR and slower DSB repair kinetics.
      CONCLUSIONS: Loss of DAB2IP expression in BCa cells signifies their
      radioresistance. KU55933, which suppresses ATM phosphorylation upon irradiation,
      could be applied in the radiotherapy of BCa patients with a DAB2IP gene defect.

PMID- 25585819
TI  - Erratum to: California's nurse-to-patient ratio law and occupational injury.

PMID- 25585818
TI  - Heart rate variability in male shift workers in automobile manufacturing
      factories in South Korea.
AB  - PURPOSE: The aim of this study was to determine the effect of circadian rhythm
      disruption on cardiovascular autonomic regulation by examining potential
      differences in heart rate variability (HRV) between day- and night-shift workers.
      METHODS: The study population consisted of 162 workers who worked both day and
      night shifts in two automobile manufacturing companies who underwent ambulatory
      24-h electrocardiogram recording and completed questionnaires and sleep diaries.
      Both time and frequency domain indices of HRV were compared. RESULTS: HRV
      parameters (mean RR, SDNN, RMSSD, pNN50, TP, HF, LF, LF/HF ratio) reflecting
      sympathetic and parasympathetic modulation varied less with activity in night
      shift workers. CONCLUSIONS: Circadian rhythm-mediated changes in autonomic
      regulation of the cardiovascular system were blunted in night-shift workers,
      which could contribute to an increased risk for cardiovascular disease in
      overnight workers.

PMID- 25585817
TI  - Estimates of utility weights in hemophilia: implications for cost-utility
      analysis of clotting factor prophylaxis.
AB  - Estimates of preference-weighted health outcomes or health state utilities are
      needed to assess improvements in health in terms of quality-adjusted life-years.
      Gains in quality-adjusted life-years are used to assess the cost-effectiveness of
      prophylactic use of clotting factor compared with on-demand treatment among
      people with hemophilia, a congenital bleeding disorder. Published estimates of
      health utilities for people with hemophilia vary, contributing to uncertainty in
      the estimates of cost-effectiveness of prophylaxis. Challenges in estimating
      utility weights for the purpose of evaluating hemophilia treatment include
      selection bias in observational data, difficulty in adjusting for predictors of
      health-related quality of life and lack of preference-based data comparing adults
      with lifetime or primary prophylaxis versus no prophylaxis living within the same
      country and healthcare system. 

PMID- 25585820
TI  - Advances in non-invasive drug delivery for atherosclerotic heart disease.
AB  - INTRODUCTION: Apart from statins, anti-platelet agents and invasive procedures,
      the anti-atherosclerotic medical weaponry for coronary heart disease (CHD) is
      scarce and only partially protects CHD patients from major adverse cardiac
      events. AREAS COVERED: Several novel non-invasive strategies are being developed
      to widen the therapeutic options. Among them, drug delivery tools were tested in
      vivo encompassing liposomes, micelles, polymeric, metallic and lipid
      nanoparticles used as carriers of statins, corticosteroids, a bisphosphonate, a
      glitazone, anti-cancer agents, a mycotoxin, a calcium channel blocker and a
      compound of traditional Chinese medicine. All preparations improved parameters
      related to atherosclerotic lesions induced in rabbits, rats and mice and reduced
      neointima formation in experiments aiming to prevent post-stenting restenosis. In
      subjects submitted to percutaneous coronary intervention, nanoparticle
      formulations of paclitaxel and alendronate showed safety but are still not
      conclusive regarding in-stent late loss. The experience of our group in
      atherosclerotic rabbits treated with non-protein lipid nanoparticles associated
      with anti-cancer drugs such as paclitaxel, etoposide and methotrexate is
      summarized, and preliminary safety data in CHD patients are anticipated. EXPERT
      OPINION: Taken together, these studies show that non-invasive drug-delivery
      systems may become promising tools to rescue CHD patients from the risks of
      severe and life-threatening lesions that should be more energetically treated.

PMID- 25585821
TI  - Regional citrate anticoagulation for renal replacement therapies in patients with
      acute kidney injury: a position statement of the Work Group "Renal Replacement
      Therapies in Critically Ill Patients" of the Italian Society of Nephrology.
AB  - Patients with acute kidney injury (AKI) on renal replacement therapy (RRT) are at
      increased risk for bleeding but usually require anticoagulation of the
      extracorporeal circuit, a key prerequisite for delivery of an adequate RRT dose.
      To this end, many anti-hemostatic strategies have been proposed, unfractionated
      heparin--with all of its significant drawbacks and complications--being the most
      common method used so far. In this clinical context, regional citrate
      anticoagulation (RCA) could represent the most promising strategy, and it has
      been endorsed by recent guidelines on AKI. The aim of this position statement is
      to critically review the current evidence on RCA for the extracorporeal circuit
      of RRT in patients with AKI, in order to provide suggestions for its application
      in clinical practice. To this purpose, the most relevant clinical studies and
      recent guidelines on AKI with special regard to anti-hemostatic strategies for
      RRT circuit maintenance have been reviewed and commented. Experts from the
      Working Group "Renal Replacement Therapies in Critically Ill Patients" of the
      Italian Society of Nephrology have prepared this position paper, which discusses
      the basic principles, advantages and drawbacks of RCA based on the available
      safety and efficacy data. Advice is given on how to use and monitor RCA in the
      different RRT modalities, in order to avoid complications while maximizing the
      delivery of the prescribed RRT dose.

PMID- 25585822
TI  - Systemic inflammation and oxidative stress in hemodialysis patients are
      associated with down-regulation of Nrf2.
AB  - BACKGROUND: Oxidative stress and inflammation are common features and the main
      mediators of progression of chronic kidney disease (CKD) and its cardiovascular
      complications. Under normal conditions, oxidative stress activates the
      transcription factor, nuclear factor E2-related factor 2 (Nrf2), which is the
      master regulator of genes encoding antioxidant and detoxifying enzymes and
      related proteins. The available data on expression of Nrf2 and its key target
      gene products in CKD patients is limited. We therefore investigated this topic in
      a group of CKD patients on hemodialysis. METHODS: Twenty adult hemodialysis (HD)
      patients (aged 54.9 +/- 15.2 years) and 11 healthy individuals (aged 50.9 +/- 8.0
      years) were enrolled. Peripheral blood mononuclear cells (PBMC) were isolated and
      processed for expression of nuclear factor-kappaB (NF-kappaB), Nrf2, heme
      oxygenase-1 and NADPH: quinoneoxidoreductase 1 (NQO1) by quantitative real-time
      polymerase chain reaction and western blot analysis. Plasma malondialdehyde (MDA)
      and tumor necrosis factor-alpha (TNF-alpha) levels were measured. RESULTS:
      Peripheral blood mononuclear cells from HD patients had significantly lower NQO1
      and Nrf2 mRNA expressions (0.58 +/- 0.35 vs. 1.13 +/- 0.64, p = 0.005), and
      significantly higher NF-kappaB expression (2.18 +/- 0.8 vs. 1.04 +/- 0.22, p =
      0.0001) compared to the healthy individuals. The NF-kappaB expression was
      inversely correlated with Nrf2 levels (r = -0.54, p < 0.01) in CKD patients.
      Plasma MDA and TNF-alpha levels were significantly higher in CKD patients than in
      the healthy individuals. CONCLUSIONS: Up-regulation of NFkappaB in the CKD
      patients' PBMC is coupled to down-regulation of Nrf2 and NQO1 expression. These
      observations are consistent with recent findings in CKD animals and point to the
      contribution of the impaired Nrf2 system in the pathogenesis of oxidative stress
      and inflammation in hemodialysis patients.

PMID- 25585823
TI  - Reversal of active glomerular lesions after immunosuppressive therapy in patients
      with IgA nephropathy: a repeat-biopsy based observation.
AB  - BACKGROUND: Reversal of active glomerular lesions after immunosuppressive
      treatment in patients with IgA nephropathy (IgAN) and their association with
      prognosis have not been well established. METHODS: Sixty patients with IgAN who
      received repeat biopsies after immunosuppressive treatment were recruited.
      Reversal of renal pathological lesions was evaluated between the first and second
      biopsy. The end-point was defined as a 30% reduction in estimated glomerular
      filtration rate (eGFR) or end-stage renal disease after the second biopsy.
      RESULTS: Active glomerular lesions, i.e. endocapillary hypercellularity (E),
      crescents (C) and necrosis (N) were markedly decreased at the second biopsy after
      immunosuppressive therapy (36.7 vs. 8.3%, p < 0.001; 85.0 vs. 25.0%, p < 0.001;
      and 51.7 vs. 3.3%, p < 0.001). Patients with E, C or N at the first biopsy but
      reversed at the second biopsy showed significantly decreased median levels of
      proteinuria and hematuria. Such clinical changes were not observed in those with
      active lesions at both biopsies. After a median follow-up of 32 months, 25.0% of
      patients reached the end-point. Repeat biopsy confirmed that only tubular
      atrophy/interstitial fibrosis was associated with the renal outcome. CONCLUSIONS:
      Active glomerular lesions can be reversed by immunosuppressive treatment in
      patients with IgAN. The reversal is accompanied by improvement in proteinuria and
      hematuria. The reversal of these lesions during the disease process may explain
      the lack of significant correlation of these lesions with clinical outcomes in
      the present study as well as in previous evaluation studies of the Oxford
      classification of IgAN.

PMID- 25585824
TI  - Peritoneal ultrafiltration in congestive heart failure-findings reported from its
      application in clinical practice: a systematic review.
AB  - INTRODUCTION: Peritoneal ultrafiltration (PUF) is proposed in the long-term
      treatment of congestive heart insufficiency. However, the data in literature
      available at present do not allow for conclusive meta-analysis.
      OBJECTIVE/MATERIALS AND METHODS: A systematic review of the literature (MEDLINE
      EMBASE, 01/01/2003-31/12/2013, studies with >=4 patients, adults, non-ESRD) to
      highlight which patients PUF has been used in, how and with what results.
      RESULTS: Consideration was given to 14 papers for a total of 471 patients. (1)
      Characteristics of the patients. Average age 71.6 years; diabetes mellitus (DM)
      47%; New York Heart Association (NYHA) class III 38.9%-class IV 59.8%; ischemic
      cardiopathy 67.8%; mean LVEF 35%. (2) PUF modality. Only continuous ambulatory
      peritoneal dialysis (CAPD) in ten studies, only APD in two studies, both in two
      studies. Overall CAPD was used in 56.2% of the pts. A single exchange of
      icodextrin was used to treat 51% of patients on CAPD. The volume of
      ultrafiltration obtained varied between 390 and 1,180 ml/die. (3) Effects of PUF.
      Significant improvement in NYHA class and reduction in hospitalizations. Survival
      at 12 months varying between 47 and 95%. Mortality seems to be associated with
      DM, higher basal glomerular filtration rate, less change in ejection fraction
      after PUF and less use of ICOs. LIMITATION: The main limitation of the selected
      studies, mostly retrospective and with a limited number of patients, remains the
      lack of clarity and uniformity of the selection criteria used. For this reason
      extrapolations about survival require extreme caution and are not currently
      possible. CONCLUSIONS: PUF improves symptomatology and reduces hospitalizations.

PMID- 25585826
TI  - Erratum to: lupus nephritis in Egyptian children: a 16-year experience.

PMID- 25585825
TI  - mTOR inhibitors for medical treatment of post-transplantation encapsulating
      peritoneal sclerosis: a favourable single center experience.
AB  - BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a serious complication in
      patients on peritoneal dialysis (PD) causing intestinal obstruction. Two
      different forms of EPS are reported: the classical one observed in patients on
      PD, and post-transplantation EPS (PostTx-EPS). The first-line therapy of
      classical and PostTx-EPS remains surgical treatment, but for both the
      complication rate and mortality are high. Recently, a few cases of EPS were
      successfully treated with inhibitors of mammalian target of rapamycin (mTORi).
      The aim of this study was to evaluate PostTx-EPS outcome in our patients,
      focusing on the potential benefit of mTORi treatment. METHODS: We performed a
      retrospective analysis on 1,048 kidney transplanted patients at our center
      between 11/2001 and 12/2011. RESULTS: In the 226 patients treated with PD at any
      time before grafting, we found 10 cases of PostTx-EPS (prevalence 4.4%). The mean
      age was 54.9 years (26-69), with a mean time on PD of 83.1 months (33-156). The
      interval between kidney transplant and EPS diagnosis was 10.5 months (4-18.9).
      Five of the ten patients were treated after the diagnosis with mTORi, with a
      favorable outcome in 4/5 cases. This result was substantially independent of
      surgical and steroid therapy, performed in 9/10 and 10/10 patients respectively.
      CONCLUSION: EPS is a serious complication but susceptible to improvement if early
      diagnosed. mTORi represent a useful option for EPS treatment. We too suggest
      adopting an immunosuppressive protocol based on mTORi, mycophenolate mofetil and
      steroids in order to prevent PostTx-EPS in transplanted patients at high risk.

PMID- 25585828
TI  - Sudden shortening of the paced AV delay: is this normal pacemaker function?

PMID- 25585827
TI  - Massive osseous and cartilaginous metaplasia of soft tissue Ewing sarcoma in
      adult: report of two cases.

PMID- 25585829
TI  - Sudden shortening of the paced AV delay: is this normal pacemaker function?

PMID- 25585831
TI  - Introduction to the special issue on factors positively associated with
      desistance for adolescents and adults who have sexually offended.

PMID- 25585832
TI  - Preface and comments on Ebola.

PMID- 25585830
TI  - Development of a group and family-based cognitive behavioural therapy program for
      youth at risk for psychosis.
AB  - OBJECTIVE: The onset of psychosis typically occurs during adolescence or early
      adulthood and can have a detrimental impact on social and cognitive development.
      Cognitive behavioural therapy (CBT) shows promise in reducing the risk of
      psychosis. Teaching families to apply CBT with their offspring may bolster
      therapeutic gains made in time-limited treatment. We developed a comprehensive
      group-and-family-based CBT (GF-CBT) program that aims to facilitate psychosocial
      recovery, decrease symptoms and prevent transition to psychosis in youth at risk.
      GF-CBT is grounded in ecological systems and cognitive theories, resilience
      models and research on information processing in delusions. The theoretical
      rationale and description of GF-CBT are presented together with a pilot study
      that evaluated the program's feasibility and explored participants' outcomes.
      METHODS: Youth ages 16-21 at risk for psychosis and their families participated
      in an open trial with pre, post and 3-month follow-up assessments conducted by an
      independent evaluator. The Comprehensive Assessment of At-Risk Mental States was
      the primary clinical outcome measure. RESULTS: All enrolled participants (n = 6)
      completed GF-CBT and all remitted from at-risk mental state (ARMS). As a group
      participants showed statistically significant decreases in attenuated psychotic
      symptoms, negative symptoms, depression, cognitive biases and improvements in
      functioning. Family members showed significant improvements in use of CBT skills,
      enhanced communication with their offspring, and greater confidence in their
      ability to help. Gains were maintained at follow-up. CONCLUSIONS: GF-CBT may
      delay or prevent transition to psychosis in youth at risk, and potentially
      facilitate recovery from ARMS. More rigorous, controlled research is needed to
      further evaluate this program.

PMID- 25585834
TI  - Subcortical language and non-language mapping in awake brain surgery: the use of
      multimodal tests.
AB  - BACKGROUND: Awake craniotomy is currently considered the gold standard to
      maximise the extent of resection and to minimise postoperative deficits in
      patients with supratentorial tumours near eloquent areas. In addition to direct
      electrical stimulation (DES) of the cortex, intraoperative subcortical mapping is
      increasingly used as it optimises the benefit-to-risk ratio by decreasing
      (permanent) postoperative neurological deficits. However, only little attention
      has been paid to subcortical mapping procedures and especially the tasks to be
      used. METHODS: In this article, language and non-language testing at the
      subcortical level is described and discussed by means of three right-handed cases
      with a glioma in the left hemisphere. To assess subcortical functions, a
      multimodal test named the Quick Mixed Test was developed (QMT). Pre-, intra- and
      postoperative test results are described and discussed in detail. RESULTS: Based
      on the analysis of these preliminary observations, a number of clinical
      recommendations for intraoperative subcortical mapping may be made: (1) the
      selection of a set of language and non-language tests needs to be tailored
      according to the functional corticosubcortical regions affected by the tumoral
      lesion and the patient's characteristics (job/hobby/daily life activities); (2)
      language and non-language tests should be presented in a multimodal and
      alternating way during subcortical stimulation since this approach enables
      screening various functions simultaneously or in a very short period of time and
      (3) spontaneous speech is a useful adjunct to standardised tests since it most
      resembles daily life conversation. CONCLUSION: Administration of multimodal tests
      during subcortical DES such as the experimental QMT may facilitate identification
      of eloquent pathways leading to avoidance of permanent neurological impairments.

PMID- 25585835
TI  - Side errors in neurosurgery and human factors training.
AB  - BACKGROUND: We previously reported on a series of side errors in cranial
      neurosurgery that occurred around the UK before the year 2006. That survey was
      prompted by a cluster of six cranial and spinal side errors that occurred in the
      neurosurgery department in Newcastle upon Tyne during the year 2006. The report
      was part of our investigation into the problem and how to solve it. METHODS: A
      human factors training programme was run in the department in response to a
      further side error. All 125 members of the neurosurgical theatre staff attended 1
      of 5 training days. Fifteen days of professional observation and coaching were
      held within the theatre suite. Time between errors was recorded. The success or
      otherwise of human factors measures such as checking and briefing was observed.
      RESULTS: A side checking system was adopted and became universal. Pre-list
      briefing meetings were adopted and quickly became widely used but took several
      years to become universal. Post-list debriefing meetings were introduced but were
      not widely adopted and quickly fell out of use. Mean time between side errors was
      2 months pre-intervention, 18 months after introducing a standardised checking
      system and 82 error free months had passed since the human factors training
      programme. CONCLUSIONS: Side errors in neurosurgery can be reduced by a
      combination of systematic checking and education. We suspect that education is
      useful in reducing error rates from low to very low but, as is generally true of
      human factor interventions, the evidence for this is soft.

PMID- 25585836
TI  - DTI-based deterministic fibre tracking of the medial forebrain bundle.
AB  - BACKGROUND: Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) was
      reported to reduce symptoms in psychiatric disorders. The aim of our study was to
      find standardised parameters for diffusion tensor imaging (DTI) based fibre
      tracking to reliably visualise the MFB. METHODS: Twenty-two cerebral hemispheres
      in 11 patients were investigated. Three different regions of interest (ROIs) were
      defined as seed regions for fibre tracking: the ipsilateral and contralateral
      superior cerebellar peduncle (SCP) and the nucleus raphe dorsalis (NRD). From
      each seed region the fibres were followed separately through the ventral
      tegmental area (VTA = second ROI) and their further courses and volumina were
      documented and compared. Minimal fibre length was set at 30 mm and the FA
      threshold at 0.12. RESULTS: The fibre tracts starting in seed regions in the
      ipsilateral SCP and the NRD follow a similar course along the lateral wall of the
      third ventricle (hypothalamus) and the anterior limb of the internal capsule
      (ALIC) to inferior fronto-medial brain areas. These fibres are in accordance with
      the course of the MFB as described in various anatomical atlases. Consistently, a
      branch leaves the main fibre tract laterally to take a course through the capsula
      externa to the temporo-parietal cortex. Fibre tracts starting from the
      contralateral SCP follow a more superior and lateral course, including the
      dentato-rubro-thalamic and the pyramidal tract. CONCLUSIONS: Deterministic fibre
      tracking with standardised ROIs provides constant and reproducible delineations
      of the medial forebrain bundle. Its visualisation might help to adjust targeting
      in DBS for psychiatric disorders.

PMID- 25585837
TI  - Characteristic anatomical conformation of the vertebral artery causing vascular
      compression against the root exit zone of the facial nerve in patients with
      hemifacial spasm.
AB  - BACKGROUND: Hemifacial spasm (HFS) is caused by tortuous offending vessels near
      the facial nerve root exit zone. However, the definitive mechanism of offending
      vessel formation remains unclear. We hypothesized that vascular angulation and
      tortuosity, probably caused by uneven vertebral artery blood flow, result in
      vascular compression of the facial nerve root exit zone. METHODS: The authors
      observed two anatomical characteristics of the vertebrobasilar arterial system in
      120 subjects in the surgical group and 188 controls. The presence of the dominant
      vertebral artery (DVA) and laterality of the vertebrobasilar junction (VBJ) were
      observed. We also analyzed the morphological characteristics of the surgical
      group showing the presence of DVA. The morphological characteristics were
      classified into three types: type I had the VBJ and DVA on the same side, type II
      had the VBJ within 2 mm of the midline, and type III had the VBJ opposite the
      DVA. RESULT: The DVA was more prevalent in the surgical group than in the control
      group (71 % versus 54 %, P < 0.05). The surgical group patients with HFS on the
      left were more likely to have a DVA on the left (P < 0.05) and with HFS on the
      right were more likely to have a DVA on the right (P < 0.01) compared with
      controls. The direction of the VBJ was more common on the same side as the DVA,
      which corresponds with the laterality of the HFS. In the surgical group with the
      DVA and HFS on the same side, type I was predominant, but in the surgical group
      with a contralateral DVA and HFS, type III was predominant. CONCLUSION: The
      presence of a DVA and shifting of the VBJ on the same side plays a role in the
      angulation and tortuosity of vessels in the perivertebrobasilar junction,
      resulting in neurovascular compression of the facial nerve root exit zone and
      thereby causing HFS.

PMID- 25585838
TI  - Clinical results of intraarterial thrombolysis according to tPA administration
      and perfusion/diffusion mismatching.
AB  - BACKGROUND: IA-Tx and advanced dynamic imaging studies have been adopted for
      ischemic stroke patient treatment. Many patients are treated with IV-tPA, but
      this treatment is not always feasible. In this study, IA-Tx was used for patients
      for whom IV-tPA was not indicated or when IV-tPA did not result in
      recanalization. METHODS: A total of 156 patients treated with IA-Tx were
      retrospectively reviewed. Of these, 72 patients were treated with a full dose of
      IV-tPA before receiving the IA-Tx; the remaining 84 patients only received IA-Tx.
      An initial imaging study using CTA and acute stroke MRI followed. Patients'
      demographics and clinical results were recorded and compared according to P/D
      mismatching and IV-tPA. RESULTS: Among P/D-mismatched patients, the
      recanalization rate was 80 % and the symptomatic intracranial hemorrhage rate was
      14.5 %, while among P/D-matched patients, the rates were 63 % and 41.3 %
      respectively (p < 0.05). A favorable clinical outcome occurred in 49.1 % of P/D
      mismatched, but only in 21.7 % of P/D-matched patients (p < 0.05). Among patients
      who were treated with IV-tPA before undergoing IA-Tx, the recanalization rate was
      79.2 % and the sICH rate was 27.8 %, while it was 71.4 % and 17.9 % in patients
      who did not receive IV-tPA (p < 0.05). CONCLUSIONS: Patients who have P/D
      mismatching and are treated with IA-Tx have higher recanalization rates and a
      greater probability of a favorable outcome than patients who have P/D matching
      and receive IA-Tx. For patients who do not undergo successful recanalization
      after IV-tPA or who are not indicated for IV-tPA, the authors recommend IA-Tx
      after undergoing appropriate imaging evaluation.

PMID- 25585839
TI  - Evaluation of dynamic parameters of thrombus formation measured on whole blood
      using rotational thromboelastometry in children undergoing cardiac surgery: a
      descriptive study.
AB  - BACKGROUND: Total thrombus formation velocity calculated using amplitude
      parameters obtained at different times could be used to estimate the
      amplification and the propagation phases observed during coagulation processes,
      and therefore might be useful to predict postoperative hemostatic products
      administration in pediatric patients. METHODS: We retrospectively analyzed data
      from 49 children <3 months of age who underwent cardiac surgery. Children <=1
      month of age routinely received fresh frozen plasma during bypass while children
      >1 month of age did not. The EXTEM parameters were used to calculate velocity
      curves using amplitudes obtained at different times, the area under the curve
      called total thrombus formation and the maximum rate of thrombus formation. These
      parameters were compared between children who received fresh frozen plasma and
      those who did not. Receiver operating characteristics curves were used to define
      variables that could be used to predict postoperative fresh frozen plasma
      transfusion. RESULTS: Total thrombus formation and maximum rate of thrombus
      formation significantly increased in children who received fresh frozen plasma
      compared to those who did not. Both total thrombus formation and maximum rate of
      thrombus formation have a better specificity to predict postoperative fresh
      frozen plasma transfusion compared to clotting time or maximal clot firmness.
      CONCLUSION: Based on this descriptive study, dynamic ROTEM((r)) parameters of
      total thrombus formation could be used to estimate the amplification and the
      propagation phases of coagulation in children. These parameters might be used in
      further well-designed study to predict the need for hemostatic products in
      children undergoing cardiac surgery with cardiopulmonary bypass.

PMID- 25585840
TI  - [Genetic information and prevention].

PMID- 25585841
TI  - Florid papillomatosis of the nipple: a rare presentation and review of the
      literature.
AB  - Florid papillomatosis (FP) of the nipple, or nipple adenoma, is a rare benign
      proliferative lesion originating from the lactiferous ducts of the nipple. It
      most commonly affects women in their fourth and fifth decades of life.
      Clinically, in most cases FP presents with serous or serosanguinous nipple
      discharge while in many cases an erythematoid or eroded lesion, a nodule or a
      swelling of the nipple may coexist thus resembling Paget's disease. We describe a
      case of FP with a very unusual clinical presentation. Diagnostic evaluation and
      management of the patient are discussed along with a review of the relevant
      literature. We conclude that FP should be always considered in the differential
      diagnosis of patients presenting with a rapidly enlarging nipple nodule even in
      the absence of any skin lesions or nipple discharge. Early diagnosis and prompt
      treatment are essential. Simple complete excision in order to eliminate the risk
      of recurrence is the treatment of choice for FP. Although in rare cases a
      coincidental ipsilateral or contralateral breast cancer has been reported, FP is
      considered as an entirely benign clinical entity associated with excellent
      prognosis. 

PMID- 25585842
TI  - Salbutamol or aminophylline for acute severe asthma: how to choose which one,
      when and why?
AB  - Acute, severe exacerbations of asthma present a challenge due to the significant
      morbidity associated with this presentation. For exacerbations that are
      refractory to initial treatments with inhaled and oral therapies, there is still
      doubt about which intravenous therapies are most likely to be helpful. beta-2
      agonists and aminophylline have differing mechanisms of action that also affect
      their adverse effects profiles and these are considered. A review of the
      available randomised control trials suggests that a bolus of intravenous
      salbutamol may reduce symptoms and hasten recovery. Aminophylline infusions may
      improve lung function, and in some studies have been shown to improve symptoms,
      but the evidence is not clear cut. Decisions about which treatment to use should
      include risk management considerations such as ease of prescription, preparation
      and administration factors and availability of high-dependency beds. 

PMID- 25585843
TI  - Historical analysis in the Journal of Pediatric Psychology.

PMID- 25585844
TI  - Ectopic megaureter inserting into seminal vesicle cyst with fistula to bladder.

PMID- 25585845
TI  - Winter studies.

PMID- 25585847
TI  - Computer tomography imaging findings of adrenal cavernous hemangiomas: a report
      of 10 cases.
AB  - BACKGROUND: Cavernous hemangiomas (CHs) of the adrenal gland are extremely rare.
      To date, only a few studies of adrenal CH imaging have been reported. PURPOSE: To
      analyze the computed tomography (CT) imaging findings of adrenal CHs. MATERIAL
      AND METHODS: Ten cases of adrenal CHs confirmed by a histopathological
      examination were retrospectively analyzed. All of the patients had undergone
      unenhanced and enhanced CT examinations, and eight had also undergone multiphase
      CT enhancement examinations. CT characteristics, including shape, size, margin,
      attenuation, and enhancement patterns, were analyzed. RESULTS: The study included
      six women and four men with a mean age of 49.2 years (age range, 25-62 years) and
      no signs of abnormal endocrine activity. The unenhanced CTs showed well-defined,
      heterogeneous (n = 8) or homogeneous (n = 2) density masses with scattered (n =
      8) or spread calcifications (n = 2) in six tumors. In the contrast-enhanced CTs,
      seven tumors appeared to be marked with heterogeneous enhancement, whereas three
      cases exhibited no obvious enhancement. The evaluation of the pattern of dynamic
      enhancement in eight patients revealed that the tumors showed early peripheral
      enhancement (n = 4), early central enhancement (n = 1), and mixed enhancement (n
      = 1) with progressive partial filling-in, and no obvious enhancement in any
      phases (n = 2). CONCLUSION: Adrenal CHs should be included in the differential
      diagnosis when an adrenal neoplasm is incidentally found and appears as a well
      defined, heterogeneous mass with calcifications and various enhancement patterns,
      including heterogeneous enhancement with characteristic progressive partial
      filling-in, as well as lack of enhancement in any phase.

PMID- 25585846
TI  - A systematic heritability analysis of the human whole blood transcriptome.
AB  - Genome-wide expression quantitative trait locus (eQTL) mapping may reveal common
      genetic variants regulating gene expression. In addition to mapping eQTLs, we
      systematically evaluated the heritability of the whole blood transcriptome in
      5,626 participants from the Framingham Heart Study. Of all gene expression
      measurements, about 40 % exhibit evidence of being heritable [hgeneExp(2) > 0, (p
      < 0.05)], the average heritability was estimated to be 0.13, and 10 % display
      hgeneExp(2) > 0.2. To identify the role of eQTLs in promoting phenotype
      differences and disease susceptibility, we investigated the proportion of
      cis/trans eQTLs in different heritability categories and discovered that genes
      with higher heritability are more likely to have cis eQTLs that explain large
      proportions of variance in the expression of the corresponding genes. Single cis
      eQTLs explain 0.33-0.53 of variance in transcripts on average, whereas single
      trans eQTLs only explain 0.02-0.07. The top cis eQTLs tend to explain more
      variance in the corresponding gene when its hgeneExp(2) is greater. Taking body
      mass index (BMI) as a case study, we cross-linked cis/trans eQTLs with both GWAS
      SNPs and differentially expressed genes for BMI. We discovered that BMI GWAS SNPs
      in 16p11.2 (e.g., rs7359397) are associated with several BMI differentially
      expressed genes in a cis manner (e.g. SULT1A1, SPNS1, and TUFM). These BMI
      signature genes explain a much larger proportion of variance in BMI than do the
      GWAS SNPs. Our results shed light on the impact of eQTLs on the heritability of
      the human whole blood transcriptome and its relations to phenotype differences.

PMID- 25585848
TI  - Comparison of volume perfusion computed tomography and contrast-enhanced
      ultrasound for assessment of therapeutic effect of transarterial
      chemoembolization in patients with hepatocellular carcinoma: a preliminary
      report.
AB  - BACKGROUND: Evaluation of transarterial chemoembolization (TACE) by using
      contrast-enhanced ultrasound (CEUS) and volume perfusion computed tomography
      (VPCT) as methods that display tumor vascularization. PURPOSE: To assess early
      results of TACE in patients with hepatocellular carcinoma (HCC) using CEUS and
      VPCT. MATERIAL AND METHODS: Twenty patients with HCC underwent CEUS and VPCT in
      the pre- and post-TACE setting (1 day). Hepatic perfusion index (HPI), arterial
      liver perfusion (ALP), blood flow (BF), and blood volume (BV) were measured with
      VPCT. Peak intensity (PI), time-to-peak (TTP), and regional blood flow (RBF) were
      measured with CEUS. Sensitivity, specificity, negative and positive predictive
      values, and cutoff values for these parameters were calculated. Immediate tumor
      response after TACE was classified as responder or non-responder. Results were
      compared with those at follow-up after 2 and 4 months (FU2mo/FU4mo) following
      modified RECIST. RESULTS: CEUS and VPCT showed comparable immediate post-TACE
      results in 20/20 cases. Complete response was confirmed in 10/20 patients at
      FU2mo and in 9/20 at FU4mo. For responders, reduction in HPI, ALP, BV, and BF at
      day 1 post TACE proved significant (P < 0.001). For non-responders, the course of
      all VPCT parameters proved non-significant. A cutoff of 40% reduction in HPI and
      a reduction in ALP of >29.6%, in BV of >41.4%, or in BF of >53.1% was indicative
      of response according to FU2mo. For responders only, changes in PI (P < 0.001),
      TTP (P < 0.01), and BF (P < 0.01) proved significant whereas for non-responders,
      all CEUS parameters proved non-significant. CONCLUSION: CEUS performs equally to
      VPCT for assessment of early response to TACE in HCC by a lesion-by-lesion
      assessment and showed prognostic value at mid-term.

PMID- 25585849
TI  - Resting-state networks in healthy adult subjects: a comparison between a 32
      element and an 8-element phased array head coil at 3.0 Tesla.
AB  - BACKGROUND: Little research exists on the influence of a magnetic resonance
      imaging (MRI) head coil's channel count on measured resting-state functional
      connectivity. PURPOSE: To compare a 32-element (32ch) and an 8-element (8ch)
      phased array head coil with respect to their potential to detect functional
      connectivity within resting-state networks. MATERIAL AND METHODS: Twenty-six
      healthy adults (mean age, 21.7 years; SD, 2.1 years) underwent resting-state
      functional MRI at 3.0 Tesla with both coils using equal standard imaging
      parameters and a counterbalanced design. Independent component analysis (ICA) at
      different model orders and a dual regression approach were performed. Voxel-wise
      non-parametric statistical between-group contrasts were determined using
      permutation-based non-parametric inference. RESULTS: Phantom measurements
      demonstrated a generally higher image signal-to-noise ratio using the 32ch head
      coil. However, the results showed no significant differences between
      corresponding resting-state networks derived from both coils (p < 0.05, FWE
      corrected). CONCLUSION: Using the identical standard acquisition parameters, the
      32ch head coil does not offer any significant advantages in detecting ICA-based
      functional connectivity within RSNs.

PMID- 25585850
TI  - Clinical value of fat-suppressed 3D volume isotropic spin-echo (VISTA) sequence
      compared to 2D sequence in evaluating internal structures of the knee.
AB  - BACKGROUND: Although many three-dimensional (3D) magnetic resonance imaging (MRI)
      sequences have been used in the clinical field, there are no studies on fat
      suppressed (FS) 3D sequences for the diagnosis of knee abnormalities. PURPOSE: To
      evaluate the usefulness of FS 3D volume isotropic turbo spin echo acquisition
      (VISTA) imaging for diagnosis of internal structures of knee. MATERIAL AND
      METHODS: In 137 patients with 138 knee MRI examinations who had undergone both FS
      3D VISTA MRI and two-dimensional (2D) MRI of the knee at 3.0 T, arthroscopic
      surgery was subsequently performed. Multiplanar reformations (MPR) of FS 3D VISTA
      images and their MPR sequences were compared with 2D MR images of axial T1
      weighted (T1W) images, axial FS T2-weighted (T2W) images, coronal FS T2W images,
      and sagittal T2W images. Two musculoskeletal radiologists reviewed the images
      independently. RESULTS: Arthroscopy revealed 33 anterior cruciate ligament tears,
      three posterior cruciate ligament tears, 42 lateral meniscus tears, and 68 medial
      meniscus tears. Five medial collateral ligament tears were clinically confirmed.
      Image acquisition time was shorter for FS 3D VISTA imaging than 2D imaging. There
      were no significant differences in diagnostic values between FS 3D VISTA and 2D
      imaging (P > 0.05). There were excellent inter-observer agreements for both FS 3D
      VISTA and 2D imaging (kappa > 0.84). CONCLUSION: FS 3D VISTA imaging could
      replace 2D imaging because of equal diagnostic ability and shorter scan time.

PMID- 25585851
TI  - Assessment of operability by means of CTPA and perfusion SPECT in patients with
      chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) can potentially
      be cured by pulmonary thrombendarterectomy (PEA), the criteria for
      differentiation between operable and non-operable patients are not standardized.
      PURPOSE: To retrospectively evaluate the value of rigidly registered computed
      tomography pulmonary angiography (CTPA) and single photon emission CT (SPECT) in
      differentiating for PEA. MATERIAL AND METHODS: Forty-nine patients with CTEPH (21
      men; age, 58 +/- 13 years) were evaluated by an interdisciplinary expert board
      using all available diagnostic information and their consensus statement as gold
      standard. For SPECT a lobe based perfusion score was visually assessed using the
      score of 0 (lack of perfusion) to 1 (normal perfusion) calculating percentage of
      vascular obstruction (PVO). By CTPA, vascular obstruction index (OI) of central,
      peripheral, and global PA-bed were determined. The accuracy of the alignment
      between CTPA and SPECT was determined by fusion score (FS) ranging from 1 (no
      alignment) to 5 (exact alignment). Angiography provided PA pressure (PAP),
      pulmonary vascular resistance (PVR), and PA wedge pressure (PAWP). Receiver
      operating characteristics (ROC) analysis was performed. RESULTS: Twenty-nine
      patients were considered surgically amenable, and 20 patients were inoperable.
      Mean PAP, PVR, and PAWP were 48 +/- 11 mmHg, 868 +/- 461 dynes*sec*cm(-5), and 11
      +/- 5 mmHg, without differences between surgical and non-surgical patients (P >
      0.5). In all patients accurate registration was reached (FS = 4.1 +/- 0.7; range,
      2-5). PVO and central OI separated PEA-amenable patients (P <= 0.001) resulting
      in the area under the curve of 0.828 (cutoff for PVO: 37.8% with a sensitivity of
      82% and specificity of 79%) and 0.755 (cutoff for central OI: 29% with a
      sensitivity and specificity of 86.2% and 79%) for operability. CONCLUSION: An
      accurate interpretation of rigidly registered CTPA and perfusion SPECT may
      contribute to stratification of operability in patients with CTEPH.

PMID- 25585852
TI  - Three-dimensional isotropic T2-weighted fast spin-echo (VISTA) knee MRI at 3.0 T
      in the evaluation of the anterior cruciate ligament injury with additional views:
      comparison with two-dimensional fast spin-echo T2-weighted sequences.
AB  - Background There has been no comparison study to assess the diagnostic efficacy
      of additional anterior cruciate ligament (ACL) views in three-dimensional (3D)
      volume isotropic turbo spin-echo acquisition (VISTA) and two-dimensional (2D)
      fast spin-echo (FSE) T2-weighted (T2W) images for the diagnosis of ACL tear.
      Purpose To compare the diagnostic performances of additional ACL views on VISTA
      with those on the 2D FSE T2W images. Material and Methods This retrospective
      study included 78 patients who were suspected to have ACL injury and underwent
      both 2D TSE T2W magnetic resonance imaging (MRI) and 3D VISTA MRI of the knee
      between November 2012 and March 2013. The diagnostic performance of each oblique
      sagittal and coronal view and the combined images was evaluated for sensitivity,
      specificity, and accuracy for diagnosing an ACL tear. The arthroscopically and
      clinically confirmed diagnoses were used as the reference standard. The values
      were statistically analyzed using the McNemar test. Results The inter-observer
      agreement between two readers of the additional ACL views on 3D VISTA and 2D FSE
      T2W images were substantial on 2D FSE images and nearly concurred on the VISTA
      image. When considering both views of the oblique sagittal and coronal images,
      the inter-observer agreement between readers nearly concurred. There were no
      statistically significant differences in the sensitivity, specificity, and
      accuracy between 2D FSE images and VISTA images. Conclusion The performance of
      the additional ACL view on 3D VISTA MRI is comparable to that of 2D FSE T2W MRI
      in the diagnosis of ACL tear though the image quality of the 3D VISTA MRI is not
      equal to that of 2D FSE MRI.

PMID- 25585853
TI  - How accurate is the label "allergic to iodinated contrast agents"?
AB  - BACKGROUND: Iodinated contrast agents (ICAs) are crucial to the use of many
      imaging studies. Reported allergies to ICAs in the medical record can interfere
      with optimal diagnostic imaging workups. PURPOSE: To investigate the accuracy
      with which the label "allergic to ICAs" is applied. MATERIAL AND METHODS: The
      medical records of 500 patients labeled "allergic to ICAs" at a single tertiary
      care hospital were reviewed. Patients were separated into three groups based on
      documentation in their medical records, as follows: Group 1, documented
      hypersensitivity reaction to ICAs; Group 2, documented ICA exposure with non
      hypersensitivity adverse event (Group 2a) or without documented reaction (Group
      2b); and Group 3, no documented prior exposure to an ICA. We then further
      reviewed the EMR to determine whether or not patients had subsequent
      administration of an ICA, whether or not they were given specific premedication,
      and whether or not they had a subsequent ICA-related event. RESULTS: A total of
      16.6% of patients (n = 83) listed as "allergic to ICAs" had a documented
      hypersensitivity reaction following ICA administration (Group 1) while 58.6% (n =
      293) of patients (Group 2) had a documented exposure to ICAs with either: (i) a
      non-hypersensitivity adverse event (23.5%, n = 69) or (ii) no record of a
      reaction to ICAs (76.5%, n = 224). The remaining 24.8% (n = 124), Group 3, had no
      record of exposure to an ICA, yet still carried the label. CONCLUSION: The
      majority of patients carrying the label "allergic to ICAs" had no record of a
      prior hypersensitivity reaction to ICAs.

PMID- 25585854
TI  - Th17- and Treg-related cytokine and mRNA expression are associated with acute and
      resolving Kawasaki disease.
AB  - BACKGROUND: Kawasaki disease is a vasculitis most commonly afflicting children <5
      years of age. Many autoimmune diseases are associated with up-regulation of T
      helper (Th) 17 cells, and down-regulation Treg cells. Few studies have examined
      the Th17/Treg expression in Kawasaki disease. METHODS: Blood samples were
      obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy,
      followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute
      febrile infectious disease and 30 healthy children were obtained as control.
      Plasma levels of Th17- and Treg-related cytokines including IL-6, IL-17A, IL-10,
      TGF-beta, and mRNA expression levels of RORgammat and Foxp3 were tested. RESULTS:
      Patients with Kawasaki disease had higher levels of plasma IL-17A (25.35 +/- 3.21
      vs 7.78 +/- 1.78 pg/ml, P < 0.001) and IL-6 (152.29 +/- 21.94 vs 38.63 +/- 12.40
      pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a
      reduction in IL-6 and IL-17A at both 3 and 21 days after IVIG therapy. FoxP3
      levels increased significantly 3 days after IVIG therapy (2.28 +/- 0.34 vs 0.88
      +/- 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL-10
      and IL-17A. CONCLUSION: Kawasaki disease was associated with higher IL-17A and IL
      6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted
      in increased expression of Treg-related FoxP3. IVIG resistance was associated
      with higher levels of IL-10 and IL-17A. Our findings provide further evidence
      that Kawasaki disease is an autoimmune-like disease.

PMID- 25585855
TI  - Distribution of astigmatism as a function of age in an Australian population.
AB  - PURPOSE: Astigmatism is a common cause of refractive error and is known to vary
      in prevalence with age. Although the search for genes associated with spherical
      refractive errors (especially myopia) has met with limited success, current
      efforts to identify genetic variants implicated in astigmatism development have
      been less rewarding. We aimed to assess the association between astigmatism and
      age to identify appropriate age cut-offs for maximizing power in genetic studies
      of astigmatism. METHODS: We performed a cross-sectional analysis of right eye
      astigmatism data from four Australian-based eye studies comprising 3841
      participants aged 5-90 years. Measurements were performed under cycloplegia using
      an autorefractor, and individuals with a history of cataract, refractive surgery
      or corneal pathology were excluded from the analysis. In addition to the
      magnitude and type (against-the-rule, with-the-rule, and oblique) of astigmatism,
      we calculated the vector components (J0 , J45 ) and evaluated the association of
      these outcome measures with age. RESULTS: The magnitude of refractive astigmatism
      (RA) remained relatively stable [mean +/- SD (-0.44 D +/- 0.50)] until
      individuals reached the age of 50, thereafter increasing in average magnitude by
      approximately 1.00 D for those subjects aged 90. In contrast, corneal astigmatism
      (CA) remained relatively stable from childhood until the age of 80 (-0.76 D +/-
      0.61). The prevalence of clinically significant RA (>=1.00 D) increased with age
      and was highest in those aged >70 years [55.1% (47.2-62.7%)]. Age was
      significantly associated with RA in adults [odds ratio (OR) = 1.04 per 1 year, p
      < 0.001]. A weaker relationship was observed between CA and age (OR = 1.007 per 1
      year, p = 0.02). CONCLUSIONS: We have confirmed the previously documented
      association between RA and age. Our results indicate that most of the observed
      change occurs after the age of 50, providing a recommended cut-off for
      participants in genetic studies of this refractive condition.

PMID- 25585857
TI  - Factors associated with risk of depression and relevant predictors of screening
      for depression in clinical practice: a cross-sectional study among HIV-infected
      individuals in Denmark.
AB  - OBJECTIVES: Depression and psychiatric disorders are frequent among HIV-infected
      individuals. The aim of this study was to determine the prevalence of depression
      and describe the psychiatric history of HIV-infected individuals in an out
      patient clinic in Denmark and to identify factors of clinical importance that may
      be used to identify patients at risk of depression. METHODS: In 2013, 212 HIV
      infected patients were included in a questionnaire study. We used the Beck
      Depression Inventory II (BDI-II) to assess the prevalence and severity of
      depressive symptoms. Patients with a BDI-II score >= 20 were offered a clinical
      evaluation by a consultant psychiatrist. Logistic regression was used to
      determine predictors associated with risk of depression. RESULTS: Symptoms of
      depression (BDI-II score >= 14) were observed in 75 patients (35%), and symptoms
      of moderate to major depression (BDI-II score >= 20) in 55 patients (26%). There
      was also a high prevalence of co-occurring mental illness. In a multivariate
      model, self-reported stress, self-reported perception that HIV infection affects
      all aspects of life, self-reported poor health, not being satisfied with one's
      current life situation, previous alcohol abuse, nonadherence to antiretroviral
      therapy and previously having sought help because of psychological problems were
      independently associated with risk of depression. CONCLUSIONS: Symptoms of
      depression and co-occurring mental illness are under-diagnosed and under-treated
      among HIV-infected individuals. We recommend that screening of depression should
      be conducted regularly to provide a full psychiatric profile to decrease the risk
      of depression and improve adherence and quality of life in this population.

PMID- 25585858
TI  - Evaluation of acceleration and deceleration cardiac processes using phase
      rectified signal averaging in healthy and idiopathic dilated cardiomyopathy
      subjects.
AB  - The aim of the present study was to investigate the suitability of the Phase
      Rectified Signal Averaging (PRSA) method for improved risk prediction in cardiac
      patients. Moreover, this technique, which separately evaluates acceleration and
      deceleration processes of cardiac rhythm, allows the effect of sympathetic and
      vagal modulations of beat-to-beat intervals to be characterized. Holter
      recordings of idiopathic dilated cardiomyopathy (IDC) patients were analyzed:
      high-risk (HR), who suffered sudden cardiac death (SCD) during the follow-up; and
      low-risk (LR), without any kind of cardiac-related death. Moreover, a control
      group of healthy subjects was analyzed. PRSA indexes were analyzed, for different
      time scales T and wavelet scales s, from RR series of 24 h-ECG recordings, awake
      periods and sleep periods. Also, the behavior of these indexes from simulated
      data was analyzed and compared with real data results. Outcomes demonstrated the
      PRSA capacity to significantly discriminate healthy subjects from IDC patients
      and HR from LR patients on a higher level than traditional temporal and spectral
      measures. The behavior of PRSA indexes agrees with experimental evidences related
      to cardiac autonomic modulations. Also, these parameters reflect more regularity
      of the autonomic nervous system (ANS) in HR patients.

PMID- 25585859
TI  - Obstetric and neonatal outcomes after preterm premature rupture of membranes
      among women carrying group B streptococcus.
AB  - OBJECTIVE: To evaluate whether carriers of group B streptococcus (GBS) have
      adverse obstetric and neonatal outcomes when preterm premature rupture of
      membranes (PPROM) occurs. METHODS: In a retrospective study, data were reviewed
      for women with a singleton pregnancy and PPROM before 34 weeks who attended the
      Meir Medical Center, Kfar Saba, Israel, between 2005 and 2012. All women received
      roxithromycin for 1 week, and ampicillin until GBS culture results were
      available. Ampicillin was continued to 1 week if the GBS culture was positive.
      The primary study outcome measure was the latency period (time from rupture of
      membranes to active/induced labor). RESULTS: Among 116 eligible patients, 21
      (18.1%) were GBS carriers and 95 (81.9%) noncarriers. The latency period was 11.2
      +/- 18.1 days for GBS carriers versus 7.5 +/- 9.6 days for noncarriers (P=0.93).
      However, there was a correlation between the length of ampicillin treatment and
      the latency period (Spearman correlation coefficient 0.7; P<0.001). There were no
      differences in early neonatal outcomes. CONCLUSION: GBS carriers with PPROM did
      not have adverse outcomes. Longer treatment with ampicillin among GBS carriers
      prolonged the latency period.

PMID- 25585860
TI  - Experiences of Power and Violence in Mexican Men Attending Mutual-Aid Residential
      Centers for Addiction Treatment.
AB  - Fundamental elements of hegemonic masculinity such as power and violence are
      analyzed through characteristics of 12-step programs and philosophy immersed in
      Mutual-Aid Residential Centers for Addiction Treatment (CRAMAAs). CRAMAAs are a
      culturally specific form of substance abuse treatment in Mexico that are
      characterized by control and violence. Fifteen interviews were carried out with
      men of varied sociodemographic characteristics, and who resided in at least two
      of these centers. Results identify that power is expressed through drug abuse and
      leads them to subsequent biopsychosocial degradation. Residency in CRAMAAs is
      motivated by women, but men do not seek the residency and are usually admitted
      unwillingly. Power through violence is carried out inside CRAMAAs where men are
      victims of abuse. From a 12-step philosophy, this violence is believed to lead
      them to a path of recovery but instead produces feelings of anger and
      frustration. The implications of these centers on Mexican public health are
      discussed.

PMID- 25585862
TI  - The study of structure and dynamics of molecules: NMR spectra transformed by
      superfine coupling.
AB  - In the present paper, the peculiarities of NMR phenomenon in paramagnetic systems
      are reported. Specifics of detection of high-resolution NMR spectra transformed
      by superfine interaction are discussed. Concrete examples illustrate the modern
      possibilities of NMR application for the study of structure and dynamics of the
      molecular (multielectron) systems.

PMID- 25585861
TI  - The Internet's Multiple Roles in Facilitating the Sexual Orientation Identity
      Development of Gay and Bisexual Male Adolescents.
AB  - One emerging avenue for the exploration of adolescents' sexual orientation
      identity development is the Internet, since it allows for varying degrees of
      anonymity and exploration. The purpose of this phenomenological study was to
      examine the role of the Internet in facilitating the sexual orientation identity
      development process of gay and bisexual male adolescents. Qualitative interviews
      were conducted with an ethnically diverse sample of 63 gay/bisexual male
      adolescents (ages 15-23). Participants reported using a range of Internet
      applications as they explored and came to accept their sexual orientation
      identity, with the intended purpose and degree of anonymity desired determining
      which applications were used. Youth reported that the Internet provided a range
      of functions with regard to the exploration and acceptance of their sexual
      orientation identity, including (1) increasing self-awareness of sexual
      orientation identity, (2) learning about gay/bisexual community life, (3)
      communicating with other gay/bisexual people, (4) meeting other gay/bisexual
      people, (5) finding comfort and acceptance with sexual orientation, and (6)
      facilitating the coming out process. Future research and practice may explore the
      Internet as a platform for promoting the healthy development of gay and bisexual
      male adolescents by providing a developmentally and culturally appropriate venue
      for the exploration and subsequent commitment to an integrated sexual orientation
      identity.

PMID- 25585863
TI  - Quantitative assessment on soil enzyme activities of heavy metal contaminated
      soils with various soil properties.
AB  - Soil enzyme activities are greatly influenced by soil properties and could be
      significant indicators of heavy metal toxicity in soil for bioavailability
      assessment. Two groups of experiments were conducted to determine the joint
      effects of heavy metals and soil properties on soil enzyme activities. Results
      showed that arylsulfatase was the most sensitive soil enzyme and could be used as
      an indicator to study the enzymatic toxicity of heavy metals under various soil
      properties. Soil organic matter (SOM) was the dominant factor affecting the
      activity of arylsulfatase in soil. A quantitative model was derived to predict
      the changes of arylsulfatase activity with SOM content. When the soil organic
      matter content was less than the critical point A (1.05% in our study), the
      arylsulfatase activity dropped rapidly. When the soil organic matter content was
      greater than the critical point A, the arylsulfatase activity gradually rose to
      higher levels showing that instead of harm the soil microbial activities were
      enhanced. The SOM content needs to be over the critical point B (2.42% in our
      study) to protect its microbial community from harm due to the severe Pb
      pollution (500mgkg(-1) in our study). The quantitative model revealed the pattern
      of variation of enzymatic toxicity due to heavy metals under various SOM
      contents. The applicability of the model under wider soil properties need to be
      tested. The model however may provide a methodological basis for ecological risk
      assessment of heavy metals in soil.

PMID- 25585864
TI  - Impact of kerosene space heaters on indoor air quality.
AB  - In recent years, the use of kerosene space heaters as additional or principal
      heat source has been increasing, because these heaters allow a continuous control
      on the energy cost. These devices are unvented, and all combustion products are
      released into the room where the heaters are operated. The indoor air quality of
      seven private homes using wick-type or electronic injection-type kerosene space
      heaters was investigated. Concentrations of CO, CO2, NOx, formaldehyde and
      particulate matter (0.02-10 MUm) were measured, using time-resolved instruments
      when available. All heaters tested are significant sources of submicron
      particles, NOx and CO2. The average NO2 and CO2 concentrations are determined by
      the duration of use of the kerosene heaters. These results stress the need to
      regulate the use of unvented combustion appliances to decrease the exposure of
      people to air contaminants.

PMID- 25585865
TI  - Impact of oxy-fuel combustion gases on mercury retention in activated carbons
      from a macroalgae waste: effect of water.
AB  - The aim of this study is to understand the different sorption behaviors of
      mercury species on activated carbons in the oxy-fuel combustion of coal and the
      effect of high quantities of water vapor on the retention process. The work
      evaluates the interactions between the mercury species and a series of activated
      carbons prepared from a macroalgae waste (algae meal) from the agar-agar industry
      in oxy-combustion atmospheres, focussing on the role that the high concentration
      of water in the flue gases plays in mercury retention. Two novel aspects are
      considered in this work (i) the impact of oxy-combustion gases on the retention
      of mercury by activated carbons and (ii) the performance of activated carbons
      prepared from biomass algae wastes for this application. The results obtained at
      laboratory scale indicate that the effect of the chemical and textural
      characteristics of the activated carbons on mercury capture is not as important
      as that of reactive gases, such as the SOx and water vapor present in the flue
      gas. Mercury retention was found to be much lower in the oxy-combustion
      atmosphere than in the O2+N2 (12.6% O2) atmosphere. However, the oxidation of
      elemental mercury (Hg0) to form oxidized mercury (Hg2+) amounted to 60%,
      resulting in an enhancement of mercury retention in the flue gas desulfurization
      units and a reduction in the amalgamation of Hg0 in the CO2 compression unit.
      This result is of considerable importance for the development of technologies
      based on activated carbon sorbents for mercury control in oxy-combustion
      processes.

PMID- 25585866
TI  - A novel method for measuring polymer-water partition coefficients.
AB  - Low density polyethylene (LDPE) often is used as the sorbent material in passive
      sampling devices to estimate the average temporal chemical concentration in water
      bodies or sediment pore water. To calculate water phase chemical concentrations
      from LDPE concentrations accurately, it is necessary to know the LDPE-water
      partition coefficients (KPE-w) of the chemicals of interest. However, even
      moderately hydrophobic chemicals have large KPE-w values, making direct
      measurement experimentally difficult. In this study we evaluated a simple three
      phase system from which KPE-w can be determined easily and accurately. In the
      method, chemical equilibrium distribution between LDPE and a surfactant micelle
      pseudo-phase is measured, with the ratio of these concentrations equal to the
      LDPE-micelle partition coefficient (KPE-mic). By employing sufficient mass of
      polymer and surfactant (Brij 30), the mass of chemical in the water phase remains
      negligible, albeit in equilibrium. In parallel, the micelle-water partition
      coefficient (Kmic-w) is determined experimentally. KPE-w is the product of KPE
      mic and Kmic-w. The method was applied to measure values of KPE-w for 17
      polycyclic aromatic hydrocarbons, 37 polychlorinated biphenyls, and 9
      polybrominated diphenylethers. These values were compared to literature values.
      Mass fraction-based chemical activity coefficients (gamma) were determined in
      each phase and showed that for each chemical, the micelles and LDPE had nearly
      identical affinity. 

PMID- 25585867
TI  - Potential genotoxicity and risk assessment of a chlorinated flame retardant,
      Dechlorane Plus.
AB  - Dechlorane Plus (DP) is a chlorinated flame retardants that is globally
      ubiquitous. It is a potentially persistent organic pollutant (POPs) and an
      environmental toxin. However, the toxicity data is still limited and cannot
      provide a comprehensive environmental ecological risk assessment for DP. In this
      study, luminous bacteria, Vicia faba and Tetrahymena thermophila were chosen as
      testing organisms to investigate the acute toxicity and mutagenicity of DP. The
      concentration gradient of DP used in this study was chosen based on its
      environmental levels (experiments of luminous bacteria: 0.591, 2.95, 14.8, 73.8,
      369 MUg L(-1); micronucleus tests: 2.4, 12, 60, 300, 1500 MUg L(-1); comet assay:
      2.4, 12, 60, 300, 1500 MUg L(-1)). For luminous bacteria, the relative
      luminosities were around 100% in treated groups, which suggested that there is no
      acute toxicity to luminous bacteria under the studied DP concentrations. The
      micronucleus test showed no significant difference between treatment and control
      groups, indicating no genotoxicity of DP. However the comet assay conducted with
      T. thermophila was relatively sensitive as there was a significant increase in
      DNA damage when the concentrations of DP increased from 300 to 1500 MUg L(-1),
      while the lower concentrations failed to show any treatment-related differences.
      Therefore, DP may pose a potential risk at concentration?300 MUg L(-1). The
      results provide scientific information on the ecological risk assessment of DP.

PMID- 25585868
TI  - Persistent phototransformation products of vardenafil (Levitra(r)) and sildenafil
      (Viagra(r)).
AB  - As pharmaceutically active compounds (PhACs) are increasingly detected in the
      aquatic environment, the importance of investigating their transformation
      products-products of naturally occurring hydrolysis, biodegradation, and solar
      mediated photochemical reactions - for persistence and ecotoxicity remains an
      important part of assessing the pharmaceutical's environmental impact and fate.
      In this study, the solar phototransformation of vardenafil (active ingredient in
      Levitra(r)) and sildenafil (Viagra(r)), two structurally similar compounds used
      to treat erectile dysfunction, was studied, with special attention to potentially
      persistent phototransformation (PT) products. PT products for vardenafil are
      identified here for the first time. Dilute solutions were prepared in buffered
      (pH=7.4) aqueous solutions, both with and without Suwanee River humic acid (SRHA)
      and fulvic acid (SRFA), and exposed to simulated sunlight. The PT products were
      identified via Liquid Chromatography-Electrospray Ionization-Mass Spectrometry
      (LC-ESI-MS) and confirmed by MS/MS. Both SRHA and SRFA were observed to lead to
      more extensive degradation of VRD while having minimal effect on SLD. At least
      two PT products, SLD-392 and VRD-392, were observed to be notably persistent,
      indicating their potential impact in the aquatic environment and highlighting the
      need for investigations of transformation products in natural water samples. 

PMID- 25585869
TI  - Carbon isotopic fractionation during biodegradation of phthalate esters in anoxic
      condition.
AB  - Here we evaluate the quantitative relationship between carbon isotopic
      fractionation and anoxic biodegradation of phthalate esters (PAEs), a kind of
      endocrine disruptors. The stable carbon isotope delta values (delta(13)C) of 4
      PAEs, i.e. di-methyl phthalate (DMP), di-ethyl phthalate (DEP), di-n-butyl
      phthalate (DBP), and di-iso-butyl phthalate (DiBP), were analyzed during
      biodegradation by a pure bacteria strain isolated from the shallow aquifer
      sediment in anoxic condition. Results showed that the carbon isotopic
      fractionation in the initial degradation of PAEs was well-described by the
      Rayleigh equation model with R(2) from 0.8885 to 0.9821. The carbon isotopic
      fractionation (epsilon) for DMP and DEP were -4.6+/-0.40/00 and -2.9+/-0.10/00,
      respectively, while DBP and DiBP showed limited isotopic fractionation. A linear
      relationship between epsilon values and the total carbon atoms present in
      straight-carbon-chain PAE molecules with R(2) of 0.9918. The apparent kinetic
      isotope effects (AKIEs) were calculated for proposed 4 initial transformation
      pathways of PAEs. The high carbon AKIEs of 1.048 and 1.036 were obtained for
      single enzymatic hydrolysis of DMP and DEP, respectively, and fell in the
      expected KIE range of 1.03-1.09. However, the intrinsic carbon isotope effects
      for enzymatic hydrolysis of DBP and DiBP might be masked. 

PMID- 25585870
TI  - Mixing regime as a key factor to determine DON formation in drinking water
      biological treatment.
AB  - Dissolved organic nitrogen (DON) can act as precursor of nitrogenous disinfection
      by-products formed during chlorination disinfection. The performances of
      biological fluidized bed (continuous stirred tank reactor, CSTR) and bio-ceramic
      filters (plug flow reactor, PFR) were compared in this study to investigate the
      influence of mixing regime on DON formation in drinking water treatment. In the
      shared influent, DON ranged from 0.71mgL(-1) to 1.20mgL(-1). The two biological
      fluidized bed reactors, named BFB1 (mechanical stirring) and BFB2 (air
      agitation), contained 0.12 and 0.19mgL(-1) DON in their effluents, respectively.
      Meanwhile, the bio-ceramic reactors, labeled as BCF1 (no aeration) and BCF2 (with
      aeration), had 1.02 and 0.81mgL(-1) DON in their effluents, respectively.
      Comparative results showed that the CSTR mixing regime significantly reduced DON
      formation. This particular reduction was further investigated in this study. The
      viable/total microbial biomass was determined with propidium monoazide
      quantitative polymerase chain reaction (PMA-qPCR) and qPCR, respectively. The
      results of the investigation demonstrated that the microbes in BFB2 had higher
      viability than those in BCF2. The viable bacteria decreased more sharply than the
      total bacteria along the media depth in BCF2, and DON in BCF2 accumulated in the
      deeper media. These phenomena suggested that mixing regime determined DON
      formation by influencing the distribution of viable, total biomass, and ratio of
      viable biomass to total biomass.

PMID- 25585871
TI  - Activated carbon electrodes: electrochemical oxidation coupled with desalination
      for wastewater treatment.
AB  - The wastewater usually contains low-concentration organic pollutants and some
      inorganic salts after biological treatment. In the present work, the possibility
      of simultaneous removal of them by combining electrochemical oxidation and
      electrosorption was investigated. Phenol and sodium chloride were chosen as
      representative of organic pollutants and inorganic salts and a pair of activated
      carbon plate electrodes were used as anode and cathode. Some important working
      conditions such as oxygen concentration, applied potential and temperature were
      evaluated to reach both efficient phenol removal and desalination. Under
      optimized 2.0 V of applied potential, 38 degrees C of temperature, and 500 mL
      min(-1) of oxygen flow, over 90% of phenol, 60% of TOC and 20% of salinity were
      removed during 300 min of electrolysis time. Phenol was removed by both
      adsorption and electrochemical oxidation, which may proceed directly or
      indirectly by chlorine and hypochlorite oxidation. Chlorophenols were detected as
      degradation intermediates, but they were finally transformed to carboxylic acids.
      Desalination was possibly attributed to electrosorption of ions in the pores of
      activated carbon electrodes. The charging/regeneration cycling experiment showed
      good stability of the electrodes. This provides a new strategy for wastewater
      treatment and recycling.

PMID- 25585873
TI  - Isolation and synthesis of polyoxygenated dibenzofurans possessing biological
      activity.
AB  - Reports from the past ten years describing the isolation and/or synthesis of
      bioactive dibenzofurans possessing three or more oxygen-containing substituents
      are reviewed. Dibenzofuranoquinones are included in the review. 

PMID- 25585872
TI  - SAPHO syndrome: a review.
AB  - INTRODUCTION: Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) is an
      acronym for various osteoarticular and dermatological manifestations that can
      appear in the same patient. It is a rare syndrome, but since its awareness has
      increased, there have been more and more such reports in the literature. AIMS:
      The objectives of this review are to summarize the current state of knowledge on
      pediatric and adult-onset SAPHO syndrome, and to discuss treatment strategies
      that should be considered. RESULTS: The SAPHO syndrome can affect patients of any
      age, and its etiology is still not known. The syndrome has its cognizable
      radiological characteristics that are most important in making the diagnosis.
      There are several diagnostic criteria as well, but they need further validation.
      No standard treatment protocols are available and current treatment options are
      not evidenced-based due to the rarity of the syndrome. Therapy is empirical and
      aimed at easing pain and modifying the inflammatory process. It includes
      nonsteroidal anti-inflammatory drugs (NSAIDs) as the first-line agents.
      Antibiotics, corticosteroids, disease-modifying anti-rheumatic drugs, biologicals
      targeting tumor necrosis factor alpha or interleukin-1, and bisphosphonates have
      all been used with variable success. Surgery is reserved to treat complications.
      Even though it is a disease with good long-term prognosis, its treatment remains
      a challenge and the results are known to be disappointing, especially with the
      skin component of the disease. CONCLUSION: It is expected that these patients
      present at the time of diagnosis and the treatment should be as early, effective,
      and safe as possible in order to prevent osteoarticular progression and to limit
      the adverse events associated with pharmacological drugs.

PMID- 25585874
TI  - Promoter DNA methylation and expression levels of HOXA4, HOXA5 and MEIS1 in acute
      myeloid leukemia.
AB  - HOXA genes encode transcription factors, which are crucial for embryogenesis and
      tissue differentiation and are involved in the early stages of hematopoiesis.
      Aberrations in HOXA genes and their cofactor MEIS1 are found in human neoplasms,
      including acute myeloid leukemia (AML). The present study investigated the role
      of HOXA4, HOXA5 and MEIS1 promoter DNA methylation and mRNA expression in AML.
      Samples from 78 AML patients and 12 normal bone marrow (BM) samples were
      included. The levels of promoter DNA methylation were determined using
      quantitative methylation-specific polymerase chain reaction (PCR; qMSP) and the
      relative expression levels were measured using reverse transcription quantitative
      PCR in Ficoll-separated BM mononuclear cells and in fluorescent activated cell
      sorting-sorted populations of normal hematopoietic progenitors. In total, 38.1
      and 28.9% of the patients exhibited high methylation levels of HOXA4 and HOXA5,
      respectively, compared with the control samples, and MEIS1 methylation was almost
      absent. An inverse correlation between HOXA4 methylation and expression was
      identified in a group of patients with a normal karyotype (NK AML). An
      association between the genes was observed and correlation between the DNA
      methylation and expression levels of the HOXA gene promoter with the expression
      of MEIS1 was observed. Patients with favorable chromosomal aberrations revealed a
      low level of HOXA4 methylation and decreased expression levels of HOXA5 and MEIS1
      compared with the NK AML and the adverse cytogenetic risk patients. The NK AML
      patients with NPM1 mutations exhibited elevated HOXA4 methylation and expression
      levels of HOXA5 and MEIS1 compared with the NPM1 wild-type patients. Comparison
      of the undifferentiated BM-derived hematopoietic CD34+CD38low, CD34+CD38+ and
      CD15+ cells revealed a gradual decrease in the expression levels of these three
      genes and an increase in HOXA4 promoter methylation. This differentiation
      associated variability was not observed in AML, which was classified according to
      the French-American-British system.

PMID- 25585876
TI  - Cytokine and proinflammatory gene expression in classical Hodgkin lymphoma: its
      more than NF-kappaB!

PMID- 25585877
TI  - The relationship between CCR6 and its binding partners: does the CCR6-CCL20 axis
      have to be extended?
AB  - Chemokines and their receptors are vital for the trafficking of immune cells. In
      an orchestrated fashion, up- and down-regulation of chemokines and their
      receptors contribute to both immune system homeostasis as well as inflammation.
      The CC chemokine, CCL20 and its cognate receptor, CCR6, are described as one of
      the few chemokine-receptor pairs that show exclusivity. In our review, we analyze
      observations which indicate that CCR6 does not have CCL20 as an exclusive ligand
      as once appreciated. For example, attempts to study the pair, utilizing mainly
      CCR6-deficient mice, are confounded by a family of non-chemokine ligands known as
      beta-defensins that can bind to CCR6 and potentially can activate the cell.
      Therefore, a review of the activities of other potential binding partners of CCR6
      is essential for interpretation of the current literature on this matter and for
      an understanding of their involvement in basic immunology and pathology. 

PMID- 25585875
TI  - Cytokines in psoriasis.
AB  - Psoriasis is a common inflammatory skin disease with an incompletely understood
      etiology. The disease is characterized by red, scaly and well-demarcated skin
      lesions formed by the hyperproliferation of epidermal keratinocytes. This
      hyperproliferation is driven by cytokines secreted by activated resident immune
      cells, an infiltrate of T cells, dendritic cells and cells of the innate immune
      system, as well as the keratinocytes themselves. Psoriasis has a strong
      hereditary character and has a complex genetic background. Genome-wide
      association studies have identified polymorphisms within or near a number of
      genes encoding cytokines, cytokine receptors or elements of their signal
      transduction pathways, further implicating these cytokines in the psoriasis
      pathomechanism. A considerable number of inflammatory cytokines have been shown
      to be elevated in lesional psoriasis skin, and the serum concentrations of a
      subset of these also correlate with psoriasis disease severity. The combined
      effects of the cytokines found in psoriasis lesions likely explain most of the
      clinical features of psoriasis, such as the hyperproliferation of keratinocytes,
      increased neovascularization and skin inflammation. Thus, understanding which
      cytokines play a pivotal role in the disease process can suggest potential
      therapeutic targets. A number of cytokines have been therapeutically targeted
      with success, revolutionizing treatment of this disease. Here we review a number
      of key cytokines implicated in the pathogenesis of psoriasis. 

PMID- 25585879
TI  - Light-triggered capture and release of DNA and proteins by host-guest binding and
      electrostatic interaction.
AB  - The development of an effective and general delivery method that can be applied
      to a large variety of structurally diverse biomolecules remains a bottleneck in
      modern drug therapy. Herein, we present a supramolecular system for the dynamic
      trapping and light-stimulated release of both DNA and proteins. Self-assembled
      ternary complexes act as nanoscale carriers, comprising vesicles of amphiphilic
      cyclodextrin, the target biomolecules and linker molecules with an azobenzene
      unit and a charged functionality. The non-covalent linker binds to the
      cyclodextrin by host-guest complexation with the azobenzene. Proteins or DNA are
      then bound to the functionalized vesicles through multivalent electrostatic
      attraction. The photoresponse of the host-guest complex allows a light-induced
      switch from the multivalent state that can bind the biomolecules to the low
      affinity state of the free linker, thereby providing external control over the
      cargo release. The major advantage of this delivery approach is the wide variety
      of targets that can be addressed by multivalent electrostatic interaction, which
      we demonstrate on four types of DNA and six different proteins. 

PMID- 25585878
TI  - The microbiome mutiny hypothesis: can our microbiome turn against us when we are
      old or seriously ill?
AB  - BACKGROUND: The symbiotic organisms of the healthy microbiome tend to be harmless
      or even beneficial for the host; however, some symbionts are able to adjust their
      virulence in response to external stimuli. Evolutionary theory suggests that
      optimal virulence might increase if the mortality of the host (from unrelated
      causes) increases. PRESENTATION OF THE HYPOTHESIS: We hypothesize that
      microorganisms of the human microbiome may be capable of a coordinated phenotypic
      switch to higher virulence ("microbiome mutiny") in old or seriously ill people,
      to optimize their transmission under the conditions of increased background
      mortality. This proposed virulence shift might contribute to the death of old or
      seriously ill people even in the absence of apparent disease. TESTING THE
      HYPOTHESIS: Testable predictions of the hypothesis include increased expression
      of virulence factors in isolates of the same species of the microbiome obtained
      from ailing/old versus healthy/young individuals, and the existence of microbial
      mechanisms to assess the general condition (background mortality) of the host.
      Such tests are going to be important to distinguish the cases of "microbiome
      mutiny" from the situation where opportunistic infections or increased effective
      virulence arise from relaxed immune control in ailing or old individuals in the
      absence of changes in the symbionts/pathogens. IMPLICATIONS OF THE HYPOTHESIS:
      Elucidating this potential mechanism might open up new possibilities for the
      clinical management of age related health issues and critical injuries or
      disease. Targeted prophylaxis against the microbes capable of virulence shifts
      could break the harmful feedback loop between deteriorating health and the
      "mutiny" of the microbiome.

PMID- 25585880
TI  - Relationship between linear type and fertility traits in Nguni cows.
AB  - The objective of the study was to assess the dimensionality of seven linear
      traits (body condition score, body stature, body length, heart girth, navel
      height, body depth and flank circumference) in Nguni cows using factor analysis
      and indicate the relationship between the extracted latent variables and calving
      interval (CI) and age at first calving (AFC). The traits were measured between
      December 2012 and November 2013 on 1559 Nguni cows kept under thornveld,
      succulent karoo, grassland and bushveld vegetation types. Low partial
      correlations (-0.04 to 0.51), high Kaiser statistic for measure of sampling
      adequacy scores and significance of the Bartlett sphericity test (P1. Factor 1
      included body condition score, body depth, flank circumference and heart girth
      and represented body capacity of cows. Factor 2 included body length, body
      stature and navel height and represented frame size of cows. CI and AFC decreased
      linearly with increase of factor 1. There was a quadratic increase in AFC as
      factor 2 increased (P<0.05). It was concluded that the linear type traits under
      study can be grouped into two distinct factors, one linked to body capacity and
      the other to the frame size of the cows. Small-framed cows with large body
      capacities have shorter CI and AFC. 

PMID- 25585883
TI  - Rhodium/chiral diene-catalyzed asymmetric 1,4-addition of arylboronic acids to
      chromones: a highly enantioselective pathway for accessing chiral flavanones.
AB  - Chromone has been noted to be one of the most challenging substrates in the
      asymmetric 1,4-addition of alpha,beta-unsaturated carbonyl compounds. By
      employing the rhodium complex associated with a chiral diene ligand, (R,R)-Ph
      bod*, the 1,4-addition of a variety of arylboronic acids was realized to give
      high yields of the corresponding flavanones with excellent enantioselectivities
      (>=97% ee, 99% ee for most substrates). Ring-opening side products, which would
      lead to erosion of product enantioselectivity, were not observed under the stated
      reaction conditions.

PMID- 25585881
TI  - Rapid and inexpensive whole-genome genotyping-by-sequencing for crossover
      localization and fine-scale genetic mapping.
AB  - The reshuffling of existing genetic variation during meiosis is important both
      during evolution and in breeding. The reassortment of genetic variants relies on
      the formation of crossovers (COs) between homologous chromosomes. The pattern of
      genome-wide CO distributions can be rapidly and precisely established by the
      short-read sequencing of individuals from F2 populations, which in turn are
      useful for quantitative trait locus (QTL) mapping. Although sequencing costs have
      decreased precipitously in recent years, the costs of library preparation for
      hundreds of individuals have remained high. To enable rapid and inexpensive CO
      detection and QTL mapping using low-coverage whole-genome sequencing of large
      mapping populations, we have developed a new method for library preparation along
      with Trained Individual GenomE Reconstruction, a probabilistic method for
      genotype and CO predictions for recombinant individuals. In an example case with
      hundreds of F2 individuals from two Arabidopsis thaliana accessions, we resolved
      most CO breakpoints to within 2 kb and reduced a major flowering time QTL to a 9
      kb interval. In addition, an extended region of unusually low recombination
      revealed a 1.8-Mb inversion polymorphism on the long arm of chromosome 4. We
      observed no significant differences in the frequency and distribution of COs
      between F2 individuals with and without a functional copy of the DNA helicase
      gene RECQ4A. In summary, we present a new, cost-efficient method for large-scale,
      high-precision genotyping-by-sequencing. 

PMID- 25585884
TI  - Inflammatory reaction to brown pigment in a tattoo.

PMID- 25585885
TI  - Random calibration for accelerating MR-ARFI guided ultrasonic focusing in
      transcranial therapy.
AB  - Transcranial focused ultrasound is a promising therapeutic modality. It consists
      of placing transducers around the skull and emitting shaped ultrasound waves that
      propagate through the skull and then concentrate on one particular location
      within the brain. However, the skull bone is known to distort the ultrasound
      beam. In order to compensate for such distortions, a number of techniques have
      been proposed recently, for instance using Magnetic Resonance Imaging feedback.
      In order to fully determine the focusing distortion due to the skull, such
      methods usually require as many calibration signals as transducers, resulting in
      a lengthy calibration process. In this paper, we investigate how the number of
      calibration sequences can be significantly reduced, based on random measurements
      and optimization techniques. Experimental data with six human skulls demonstrate
      that the number of measurements can be up to three times lower than with the
      standard methods, while restoring 90% of the focusing efficiency. 

PMID- 25585886
TI  - Characterisation of ship diesel primary particulate matter at the molecular level
      by means of ultra-high-resolution mass spectrometry coupled to laser desorption
      ionisation--comparison of feed fuel, filter extracts and direct particle
      measurements.
AB  - In this study, positive-mode laser desorption-ionisation ultra-high-resolution
      mass spectrometry (LDI-FT-ICR-MS) was applied to study combustion aerosol samples
      obtained from a ship diesel engine as well as the feed fuel, used to operate the
      engine. Furthermore, particulate matter was sampled from the exhaust tube using
      an impactor and analysed directly from the impaction foil without sample
      treatment. From the high percentage of shared sum formula as well as similarities
      in the chemical spread of aerosol and heavy fuel oil, results indicate that the
      primary aerosol mainly consists of survived, unburned species from the feed fuel.
      The effect of pyrosynthesis could be observed and was slightly more pronounced
      for the CH-class compared to other compound classes, but in summary not dominant.
      Alkylation pattern as well as the aromaticity distribution, using the double bond
      equivalent, revealed a shift towards lower alkylation state for the aerosol. The
      alkylation pattern of the most dominant series revealed a higher correlation
      between different aerosol samples than between aerosol and feed samples. This was
      confirmed by cluster analysis. Overall, this study shows that LDI-FT-ICR-MS can
      be successfully applied for the analysis of combustion aerosol at the molecular
      level and that sum formula information can be used to identify chemical
      differences between aerosol and fuel as well as between different size fractions
      of the particulate matter. 

PMID- 25585882
TI  - Endocannabinoid signalling in innate and adaptive immunity.
AB  - The immune system can be modulated and regulated not only by foreign antigens but
      also by other humoral factors and metabolic products, which are able to affect
      several quantitative and qualitative aspects of immunity. Among these,
      endocannabinoids are a group of bioactive lipids that might serve as secondary
      modulators, which when mobilized coincident with or shortly after first-line
      immune modulators, increase or decrease many immune functions. Most immune cells
      express these bioactive lipids, together with their set of receptors and of
      enzymes regulating their synthesis and degradation. In this review, a synopsis of
      the manifold immunomodulatory effects of endocannabinoids and their signalling in
      the different cell populations of innate and adaptive immunity is appointed, with
      a particular distinction between mice and human immune system compartments.

PMID- 25585887
TI  - Development and validation of a generic method for quantification of collagen in
      food supplement tablets using liquid chromatography coupled with time-of-flight
      mass spectrometry.
AB  - A generic method for the quantification of type II collagen in protein-based
      dietary supplements is described. This quantitative analysis was conducted using
      liquid chromatography-electrospray ionization-time-of-flight mass spectrometry
      (LC-ESI-TOF MS). Compared to classical methods with the use of isotope-labeled
      standards, our method includes, for the first time, the quantification of
      hydroxyproline using histidine as an internal standard. Separation of the
      analytes was performed on a Phenomenex Synergi 4 MUm Fusion-RP 80 A column (150 *
      2.0 mm, 4.0 MUm) with a mobile phase made of 10 mM ammonium formate in water (A)
      and 10 mM ammonium formate in methanol (B). The assay was fully validated
      according to FDA guidelines, and the method exhibited sufficient specificity,
      accuracy, and precision. Intra- and inter-batch accuracy, determined as a
      deviation between nominal and measured values, ranged from -4.8 to 9.1% and from
      0.9 to 6.4 %, respectively. All analytes (hydroxyproline and histidine) at three
      concentration levels showed extraction recoveries from 89 to 98 %. The method was
      successfully applied to protein-based dietary supplements of the pharmaceutical
      industry. 

PMID- 25585888
TI  - Editorial comment to Nomograms incorporating serum C-reactive protein effectively
      predict mortality before and after surgical treatment of renal cell carcinoma.

PMID- 25585889
TI  - Impact of bilirubin-induced neurologic dysfunction on neurodevelopmental
      outcomes.
AB  - Bilirubin-induced neurologic dysfunction (BIND) is the constellation of
      neurologic sequelae following milder degrees of neonatal hyperbilirubinemia than
      are associated with kernicterus. Clinically, BIND may manifest after the neonatal
      period as developmental delay, cognitive impairment, disordered executive
      function, and behavioral and psychiatric disorders. However, there is controversy
      regarding the relative contribution of neonatal hyperbilirubinemia versus other
      risk factors to the development of later neurodevelopmental disorders in children
      with BIND. In this review, we focus on the empiric data from the past 25 years
      regarding neurodevelopmental outcomes and BIND, including specific effects on
      developmental delay, cognition, speech and language development, executive
      function, and the neurobehavioral disorders, such as attention
      deficit/hyperactivity disorder and autism. 

PMID- 25585890
TI  - Proton therapy for low-grade gliomas: Results from a prospective trial.
AB  - BACKGROUND: In this prospective study, the authors evaluated potential treatment
      toxicity and progression-free survival in patients with low-grade glioma who
      received treatment with proton radiation therapy. METHODS: Twenty patients with
      World Health Organization grade 2 glioma who were eligible for radiation therapy
      were enrolled in a prospective, single-arm trial of proton therapy. The patients
      received proton therapy at a dose of 54 Gy (relative biological effectiveness) in
      30 fractions. Comprehensive baseline and regular post-treatment evaluations of
      neurocognitive function, neuroendocrine function, and quality of life (QOL) were
      performed. RESULTS: All 20 patients (median age, 37.5 years) tolerated treatment
      without difficulty. The median follow-up after proton therapy was 5.1 years. At
      baseline, intellectual functioning was within the normal range for the group and
      remained stable over time. Visuospatial ability, attention/working memory, and
      executive functioning also were within normal limits; however, baseline
      neurocognitive impairments were observed in language, memory, and processing
      speed in 8 patients. There was no overall decline in cognitive functioning over
      time. New endocrine dysfunction was detected in 6 patients, and all but 1 had
      received direct irradiation of the hypothalamic-pituitary axis. QOL assessment
      revealed no changes over time. The progression-free survival rate at 3 years was
      85%, but it dropped to 40% at 5 years. CONCLUSIONS: Patients with low-grade
      glioma tolerate proton therapy well, and a subset develops neuroendocrine
      deficiencies. There is no evidence for overall decline in cognitive function or
      QOL.

PMID- 25585891
TI  - Bicarbonate enhances the in vitro antibiotic activity of kanamycin in Escherichia
      coli.
AB  - Growth of enteropathogenic Escherichia coli E2348/69 was inhibited by bicarbonate
      in a dose-dependent manner, showing approximately 5% growth reduction at 5 mmol
      l(-1) while kanamycin at 3.12 MUg ml(-1) inhibited growth by 15%, yet when
      kanamycin and bicarbonate were combined at these concentrations, inhibition
      increased to 80%. Unexpectedly, at bicarbonate concentrations >20 mmol l(-1)
      enhancement of the antibiotic activity virtually disappeared, i.e. there was a
      paradoxical Eagle-like effect. How bicarbonate acts is unclear, but neutral or
      alkaline pH also enhanced the activity of kanamycin. However, several differences
      indicated a separate effect of bicarbonate. First, bicarbonate inhibited growth
      more than the corresponding increments in pH. Second, at low concentration, the
      antibiotic enhancing effect of bicarbonate was stronger than the effect of pH
      alone. Third, 5 mmol l(-1) bicarbonate significantly enhanced the activity of
      kanamycin while the corresponding pH had no effect. Fourth, the Eagle-like effect
      was exclusive of bicarbonate because changes in pH did not induce an analogous
      behaviour. Notwithstanding the mechanism, the enhancing effect of bicarbonate was
      indubitable. Consequently, it seems worthwhile to explore further its potential
      to improve the efficacy of aminoglycosides and maybe even other antibiotics.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Bicarbonate at a low concentration enhanced
      the in vitro antibiotic activity of kanamycin and gentamicin. Even though the
      action mechanism of bicarbonate is hitherto unknown, it seems worthwhile to
      explore further its capacity to improve the efficacy of aminoglycosides. Clearly,
      the well-known harmful side-effects of aminoglycosides are a concern. However, it
      has recently been shown in a fish model that bicarbonate may protect ciliary
      cells against the damage caused by aminoglycosides. So, it seems possible that
      bicarbonate could help reduce aminoglycoside dosage at the same time that it
      might help lessen the damage to auditory ciliary cells in humans.

PMID- 25585892
TI  - Partial and non-adherence: we need all the help we can get.

PMID- 25585893
TI  - The study and the struggle: pain management in education and clinical practice.

PMID- 25585894
TI  - Thromboprophylaxis: striking a balance between under-treatment and over
      treatment.
AB  - Venous thromboembolism (VTE) is an important cause of morbidity and mortality
      among patients admitted to hospital. Pulmonary embolism results in 5-10% of
      deaths, and is the commonest cause of preventable deaths in hospitalised
      patients. In addition, considerable morbidity results from VTE, such as post
      thrombotic syndrome and chronic thromboembolic pulmonary hypertension. The
      economic burden resulting from VTE and its complications is high.

PMID- 25585895
TI  - On heterogeneity of treatment effects and clinical freedom.
AB  - Three decades ago, John R Hampton announced the death of clinical freedom. Since
      then, evidence-based medicine has been the predominant paradigm in clinical
      research. By applying a population-based approach, the randomised controlled
      trial has become the cornerstone for demonstrating the overall effect of a
      treatment and for developing guidelines. The new patient-centred medicine
      movement is rediscovering the important implications of heterogeneity of
      treatment effects for clinical practice and that a better understanding of such
      variability can contribute to improve health outcomes for individual patients
      through practicing a science-based clinical freedom. 

PMID- 25585896
TI  - Political will and international collaborative frameworks in infectious diseases.
AB  - The last few decades have been marked by a rapid expansion in the world?s
      population, along with an increasingly dynamic mobility of individuals. This
      accelerated global inter-connectedness enabled microorganisms to reach virtually
      any location worldwide more rapidly and efficiently than ever before, reshaping
      the global dynamics of pathogens. As a result, a local infectious disease
      outbreak anywhere in the world may almost instantaneously assume global
      dimensions, and should therefore be considered a global priority. The history of
      several infectious diseases illustrates that in addition to prophylactic and
      therapeutic medical interventions, the interplay of social, economic, and
      political factors makes a fundamental contribution to the outcome of infectious
      disease outbreaks. Furthermore, this multi- and cross-disciplinary
      interconnectedness is a key determinant of the outcome of efforts to eradicate
      vaccine-preventable infectious diseases. A combined framework that incorporates
      teachings provided by previous outbreaks, and integrates medical and biomedical
      interventions with contributions made by social, economic, and political factors,
      emerges as vital requirement of successful global public health initiatives. 

PMID- 25585897
TI  - Increasing body weight.

PMID- 25585898
TI  - Inferring the mode of origin of polyploid species from next-generation sequence
      data.
AB  - Many eukaryote organisms are polyploid. However, despite their importance,
      evolutionary inference of polyploid origins and modes of inheritance has been
      limited by a need for analyses of allele segregation at multiple loci using
      crosses. The increasing availability of sequence data for nonmodel species now
      allows the application of established approaches for the analysis of genomic data
      in polyploids. Here, we ask whether approximate Bayesian computation (ABC),
      applied to realistic traditional and next-generation sequence data, allows
      correct inference of the evolutionary and demographic history of polyploids.
      Using simulations, we evaluate the robustness of evolutionary inference by ABC
      for tetraploid species as a function of the number of individuals and loci
      sampled, and the presence or absence of an outgroup. We find that ABC adequately
      retrieves the recent evolutionary history of polyploid species on the basis of
      both old and new sequencing technologies. The application of ABC to sequence data
      from diploid and polyploid species of the plant genus Capsella confirms its
      utility. Our analysis strongly supports an allopolyploid origin of C. bursa
      pastoris about 80 000 years ago. This conclusion runs contrary to previous
      findings based on the same data set but using an alternative approach and is in
      agreement with recent findings based on whole-genome sequencing. Our results
      indicate that ABC is a promising and powerful method for revealing the evolution
      of polyploid species, without the need to attribute alleles to a homeologous
      chromosome pair. The approach can readily be extended to more complex scenarios
      involving higher ploidy levels.

PMID- 25585900
TI  - Absence of the first two zinc fingers in BCL6 causes the loss of inhibitory
      effects on cell growth.
AB  - BCL6ZF is a novel transcript of BCL6, which lacks the first two zinc fingers of
      BCL6. It has been established that BCL6 acts as a sequence-specific
      transcriptional repressor, however, the functions of BCL6ZF remain undefined. By
      generating stably overexpressed BCL6 and BCL6ZF in NCI-H1299 lung cancer cells,
      it was found that BCL6 suppressed the levels of cell growth associated with
      impaired G1 phase progression compared with those of the mock control cells.
      However, the effects of BCL6ZF on cell growth and the cell cycle were negligible.
      Further study of these results demonstrated that eight genes downstream of BCL6
      were markedly downregulated by the overexpression of BCL6, whereas BCL6ZF
      suppressed only TGFBI, indicating that the loss of the first two zinc fingers
      caused the loss of the inhibitory effects on cell growth and transcriptional
      repression. In addition, it was determined that the BCL6ZF protein was not
      degraded as easily as BCL6 protein by the ubiquitin/proteasome pathway, implying
      that the loss of the first two zinc fingers changes the three-dimensional
      structure of BCL6ZF. The results demonstrated that BCL6 and BCL6ZF had different
      role in H1299 cells both in vitro and in vivo. The loss of its inhibitory effects
      on cell growth and transcriptional repressions.

PMID- 25585901
TI  - A randomized trial of a brief intervention for obesity in college students.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: *  Brief motivational interventions
      have been found to be efficacious for obesity in older adult populations. * 
      Brief motivational interventions including delivery of personalized feedback have
      been found to be efficacious for reducing college student drinking. WHAT THIS
      STUDY ADDS: *  First study to test the efficacy of a one-session, brief
      motivational intervention for obesity among college students. *  One session
      brief motivational interventions may have an impact on the reduction of calorie
      dense foods and beverages. *  A brief, one-session motivational interview with
      personalized feedback may not be an intensive enough intervention for obesity
      treatment among college students. SUMMARY: Young adults are at an increased risk
      for weight gain as they begin college and this has implications for the onset of
      future health consequences. Brief motivational interventions (BMIs) have been
      found to be effective with college students for reducing risky health behaviours
      such as alcohol consumption, but have not been developed and tested with a
      primary goal of reducing obesity. BMIs have been developed and tested for the
      treatment of obesity and weight-related health behaviours (WRHB) in other
      populations, such as adults and adolescents, with promising results. The purpose
      of the following study was to develop and test the efficacy of a BMI for weight
      loss among overweight and obese college students. Seventy undergraduate students
      (85.7% female, 57.1% African-American) completed an assessment about WRHBs and
      then were randomized to either receive a single 60-min BMI plus a booster phone
      call or to assessment only. At 3 months post-intervention, effect sizes within
      the intervention group were twice as large as within the assessment-only group on
      reductions in high-calorie foods and beverages. However, there were no
      statistically significant differences between groups on body mass index or WRHBs.
      The one-session nature of the session might not have been enough to produce
      significant change in weight.

PMID- 25585902
TI  - Short sleep duration preferentially increases abdominal adiposity in adults:
      preliminary evidence.
AB  - What is already known about this subject *  The evidence that short sleep
      duration is another determinant of obesity is accumulating. *  Lack of sleep has
      been reported to constitute a metabolic stressor, with increased cortisol
      concentrations as the end product. What this study adds *  This is the first
      study to show that short sleep duration is associated with a preferential
      increase in abdominal adiposity in adults. SUMMARY: The aim of this 6-year
      longitudinal study was to verify whether short sleep duration preferentially
      increases abdominal adiposity in adults. A total of 276 adults, aged 18-64 years,
      from the Quebec Family Study were available for this study. Anthropometric
      measurements (body mass index and waist circumference), self-reported sleep
      duration and several covariates were assessed. A regression equation derived from
      the changes in body mass index and waist circumference of normal- and long
      duration sleepers (reference category, >= 7 h of sleep per night, n = 233) was
      used to predict the change in waist circumference of short-duration sleepers (<=6
      h of sleep per night, n = 43). Additionally, the influence of sleep duration on
      waist circumference changes was modelled by using linear regression in both sleep
      duration groups, adjusting for changes in body mass index and other covariates.
      We observed that measured (actual) changes in waist circumference were
      significantly greater than predicted changes (mean +/- SEM: 3.41 +/- 0.53 vs.
      2.69 +/- 0.51 cm, respectively, P < 0.05), implying that short-duration sleepers
      had an excess of abdominal fat accumulation over the 6-year follow-up period.
      After controlling for the changes in total adiposity as measured by body mass
      index, only short-duration sleepers gained more abdominal adiposity over 6 years.
      The present study provides evidence that short sleep duration is associated with
      preferential increases in abdominal adiposity in adults. This finding is of
      particular concern because abdominal adiposity is correlated with a number of
      metabolic anomalies.

PMID- 25585903
TI  - Maternal obesity and inpatient medication usage.
AB  - What is already known about this subject *  Maternal obesity is associated with
      an increased use of healthcare resources including medication costs in an
      outpatient setting. What this study adds *  This study shows an increase in
      inpatient medication usage associated with maternal obesity. This is the case in
      the antenatal period but not in the peripartum period. SUMMARY: Maternal obesity
      is associated with increased medical and obstetric complications. We compared the
      inpatient antenatal and peripartum medication usage in obese women to that in
      women in the normal body mass index (BMI) category. White European women with a
      singleton pregnancy were enrolled after a glucose tolerance test excluded
      diabetes mellitus at 28 weeks gestation. Weight and height were measured in the
      first trimester and BMI calculated. Records of medications administered were
      collated from patient drug charts. Of the 284 women studied, there were 97, 85
      and 102 women in the normal, overweight and obese categories, respectively.
      Delivery details across the weight categories did not vary significantly and
      Caesarean section rates were 22.7, 22.4 and 26.5%, respectively. The length of
      hospital stay postpartum for each category was similar. The administration of
      antenatal medication showed a trend towards increasing usage with increasing BMI
      category with increases in analgesic and antibiotic use. There was no difference
      in peripartum medication usage. The study showed that maternal obesity was
      associated with an increased inpatient usage of medication in the antenatal
      period. This has implications for healthcare costs particularly if the prevalence
      of maternal obesity continues to increase.

PMID- 25585904
TI  - Influence of weight discrimination on weight loss goals and self-selected weight
      loss interventions.
AB  - What is already known about this subject *  There is a discrepancy between
      clinical and patient goals for weight loss. *  Evidence suggests that some
      bariatric patients highly value, and are willing to endure hardships for weight
      loss. *  Obesity is commonly framed as an easily reversed and individual problem,
      which in turn promotes weight discrimination. What this study adds *  Patient
      beliefs about weight loss are in accordance with social understandings of obesity
      but not with current treatment options. *  Patients may not be willing to endure
      hardships for weight loss. *  Weight discrimination may relate to how patients
      approach weight loss. SUMMARY: Bariatric patients report weight loss goals, which
      are three times higher than weight loss recommended by clinicians. It is unclear
      which weight loss interventions patients feel are necessary to reach these goals
      or whether responses associate with perceptions of weight discrimination. One
      hundred fifteen patients (BMI = 40.0 +/- 6.9 kg m(-2) , age = 47.2 +/- 12.2
      years, 85% female, 77% reporting weight discrimination) were surveyed from weight
      management clinics. Participants reported ideal weight losses of 37.6 +/- 16.7 kg
      (33% of initial weight), and the majority felt weight loss could be achieved
      through lifestyle changes such as improved physical activity (80%) or diet (52%),
      with fewer reporting pharmacotherapy (8%), surgery (12%) or genetic modification
      (7%) as necessary for goal attainment. Participants selecting lifestyle changes
      or pharmacotherapy for weight loss reported ideal weight loss goals that would
      generally be achievable through surgical means (32% and 33%, respectively), and
      participants selecting surgical intervention reported ideal goals at the upper
      end of what is generally achievable with this intervention (38%). All
      participants selecting surgery or genetic modifications reported experiencing
      weight discrimination. These results indicate a disparity between weight loss
      goals and selected interventions, and suggest that weight discrimination is
      associated with the selection of potentially riskier weight loss interventions.

PMID- 25585905
TI  - Secular trends of blood pressure, body mass index, lipids and fasting glucose
      among children and adolescents in Turkey.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: *  Turkey is in a state of rapid
      transition and urbanization. There is ample evidence for an increased
      cardiovascular risk over the past two decades in Turkey. *  Obesity, dyslipidemia
      and high blood pressure in children are markers of the future burden of
      cardiovascular disease and clustering of cardiovascular risk factors starts early
      in life. *  The patterns of cardiovascular risk factors in populations are not
      static over time and the secular trends in obesity and cardiovascular risk
      factors among children and adolescents of developing countries have not been
      completely defined. WHAT THIS STUDY ADDS: *  The prevalences of obesity and high
      blood pressure have increased several folds among Turkish children and
      adolescents over the past two decades. *  The temporal trends in fasting glucose
      and lipids did not correlate with the increasing prevalence of obesity with the
      exception of HDL-C levels. *  Finally, the prevalence of metabolic syndrome has
      doubled in Turkish children and adolescents over the last two decades. Our
      findings indicate that there may be an increase in the future morbidity and
      mortality from cardiovascular disease, thrombosis, stroke and diabetes mellitus
      throughout the developing countries. SUMMARY: Patterns of cardiovascular risk
      factors and metabolic syndrome risk criteria in populations are not static over
      time. We analyzed the trends in lipid levels, blood pressure, fasting glucose and
      body mass index over the last two decades among children and adolescents. Two
      different cross-sectional studies were examined among students (ages 8-18) in
      1989 (n = 1385) and in 2008 (n = 1746). Using the international cut-off points
      and percentiles, we identified children and adolescents with elevated blood
      pressure, triglycerides, fasting glucose (>=100 mg dL(-1) ), body mass index and
      low high-density lipoprotein cholesterol (HDL-C) levels. The prevalence of
      obesity has increased several folds over the last two decades. According to the
      international criteria, 4.3% of children were obese and 15.2% were overweight in
      2008 vs. only 0.6% obese and 4.3% overweight in 1989 (P < 0.001). The prevalence
      of elevated systolic blood pressure also increased significantly among 8-12-year
      old boys and girls (28.5 vs. 15.7%, P < 0.001). The temporal trends in fasting
      glucose and lipids did not correlate with the increasing prevalence of obesity
      with the exception of HDL-C levels. Low HDL-C (<= 10th percentile) was observed
      in 16.3% in 1989 vs. 21.6% in 2008 (P = 0.016). HDL-C levels decreased
      significantly among adolescent boys. Finally, the prevalence of metabolic
      syndrome by modified National Cholesterol Education Program (NCEP) criteria has
      doubled over the last two decades (2.2 vs. 4.5%, P < 0.001). Strategies for
      combating the future cardiovascular mortality should focus on the prevention of
      obesity, high blood pressure and metabolic syndrome among children and
      adolescents.

PMID- 25585906
TI  - One size fits all? Gender as an issue in obesity.
AB  - This study investigated differences in the psychopathology of severely obese men
      and women in primary care in the North East of Ireland in comparison to clinical
      and community norms. One hundred thirty-eight participants (31.2% male and 68.8%
      female) were measured on eating disorders, depression, anxiety, self-concept and
      quality of life using standard self-report instruments. On the Eating Disorder
      Inventory, male and female scores on body dissatisfaction and female scores on
      bulimia were elevated to a degree that they did not differ significantly from
      clinical norms (P < 0.05). Female scores on the personal and social domains of
      self-concept fell significantly below community norms, whereas male scores on the
      same domains matched community levels. Significantly, more women than men scored
      in the severe range for depression and anxiety. Most female scores on the Eating
      Disorder Examination Questionnaire corresponded to clinical levels. Male
      participants reported higher quality of life overall. The findings suggest that
      gender differences should be considered regarding interventions, and that gender
      specific treatment approaches might improve treatment outcomes. Moreover,
      screening for depression and anxiety ought to be part of obesity care for women. 

PMID- 25585907
TI  - Autonomic nervous system dysfunction in obesity and Prader-Willi syndrome:
      current evidence and implications for future obesity therapies.
AB  - The autonomic nervous system (ANS) controls essential functions like breathing,
      heart rate, digestion, body temperature and hormone levels. Evidence suggests
      that ANS dysfunction is associated with adult and childhood obesity and plays a
      role in the distribution of total body fat and the development of obesity-related
      complications in humans. This review summarizes our current understanding of ANS
      involvement in the pathogenesis of obesity and Prader-Willi syndrome. Available
      evidence of ANS dysfunction in the control of energy balance is limited and, in
      some cases, contradictory. Further investigation in this area is warranted in
      order to better understand the important contributions of the ANS to regulation
      of body fat, development of obesity and its comorbidities. Results from these
      studies will guide the development of novel obesity therapeutics targeting
      specific ANS dysfunction. 

PMID- 25585908
TI  - A short clinical overview of Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a multifaceted developmental disorder most
      commonly associated with extreme hyperphagia and life-threatening obesity. PWS is
      a genetic disorder of imprinting with almost all cases occurring spontaneously.
      Behavioural and imaging studies have shown that obesity in PWS arises from
      overeating driven by a faulty satiety mechanism which manifests as an almost
      permanent state similar to starvation. With no available treatments, management
      of the eating behaviour is the only option and has two main strategies: restrict
      access to food and distract thoughts from food. In this mini review, which we
      have aimed at clinicians, we outline the main aspects of PWS including genetics,
      development of the eating behaviour and best practice approaches to management. 

PMID- 25585909
TI  - The history of obesity.

PMID- 25585899
TI  - The statistical geometry of transcriptome divergence in cell-type evolution and
      cancer.
AB  - In evolution, body plan complexity increases due to an increase in the number of
      individualized cell types. Yet, there is very little understanding of the
      mechanisms that produce this form of organismal complexity. One model for the
      origin of novel cell types is the sister cell-type model. According to this
      model, each cell type arises together with a sister cell type through
      specialization from an ancestral cell type. A key prediction of the sister cell
      type model is that gene expression profiles of cell types exhibit tree structure.
      Here we present a statistical model for detecting tree structure in
      transcriptomic data and apply it to transcriptomes from ENCODE and FANTOM5. We
      show that transcriptomes of normal cells harbour substantial amounts of
      hierarchical structure. In contrast, cancer cell lines have less tree structure,
      suggesting that the emergence of cancer cells follows different principles from
      that of evolutionary cell-type origination. 

PMID- 25585910
TI  - Animal models of multiple system atrophy.
AB  - Since their introduction in 1996, animal models of multiple system atrophy (MSA)
      have generated important insights into pathogenesis and interventional therapies.
      Toxin and genetic approaches have been used alone or in combination to replicate
      progressive motor and non-motor symptoms reflecting human neuropathology. Here,
      we review these developments and discuss the advantages and limitations of the
      MSA animal models, as well as their application in preclinical target validation.

PMID- 25585911
TI  - An efficient molybdenum disulfide/cobalt diselenide hybrid catalyst for
      electrochemical hydrogen generation.
AB  - The electroreduction of water for sustainable hydrogen production is a critical
      component of several developing clean-energy technologies, such as water
      splitting and fuel cells. However, finding a cheap and efficient alternative
      catalyst to replace currently used platinum-based catalysts is still a
      prerequisite for the commercialization of these technologies. Here we report a
      robust and highly active catalyst for hydrogen evolution reaction that is
      constructed by in situ growth of molybdenum disulfide on the surface of cobalt
      diselenide. In acidic media, the molybdenum disulfide/cobalt diselenide catalyst
      exhibits fast hydrogen evolution kinetics with onset potential of -11 mV and
      Tafel slope of 36 mV per decade, which is the best among the non-noble metal
      hydrogen evolution catalysts and even approaches to the commercial
      platinum/carbon catalyst. The high hydrogen evolution activity of molybdenum
      disulfide/cobalt diselenide hybrid is likely due to the electrocatalytic
      synergistic effects between hydrogen evolution-active molybdenum disulfide and
      cobalt diselenide materials and the much increased catalytic sites. 

PMID- 25585912
TI  - Is magnetic resonance spectroscopy capable of detecting metabolic abnormalities
      in neurofibromatosis type 1 that are not revealed in brain parenchyma of normal
      appearance?
AB  - BACKGROUND: Results of magnetic resonance spectroscopy studies in normal
      appearing brain and in non-neoplastic brain lesions in individuals with
      neurofibromatosis type 1 (NF1) have been discrepant. OBJECTIVE: We used magnetic
      resonance spectroscopy to analyze the metabolic patterns in the basal ganglia of
      patients with NF1 and examine their correlation with focal hyperintense lesions
      in T2-weighted images (T2-weighted hyperintensities). METHODS: We used magnetic
      resonance spectroscopy data of 42 individuals with NF1 (18 with and 24 without T2
      weighted hyperintensities) and 25 controls matched for gender and age. A single
      voxel technique was employed by manually placing a region of interest with a
      uniform size over a predetermined anatomical region including the globus pallidum
      and putamen (capsulolenticular region). We further analyzed the ratios of
      choline/creatine, N-acetyl aspartate (NAA)/creatine, and myoinositol/creatine
      metabolites and the occurrence of T2-weighted hyperintensities in these regions
      in individuals with NF1. RESULTS: There was a significant difference between the
      NF1 and control groups with regard to the mean values of myoinositol/creatine and
      choline/creatine, with higher metabolite values observed in the NF1 group (P <
      0.001). Only the myoinositol/creatine ratio was able to discriminate between NF1
      subgroups with and without T2-weighted hyperintensities. For the NAA/creatine
      ratio, there was no significant difference between the NF1 and the control
      groups. CONCLUSION: Magnetic resonance spectroscopy allows the characterization
      of tissue abnormalities not demonstrable in the structural images of individuals
      with NF1 through choline and myoinositol metabolite analysis. Yet the preserved
      NAA values argue against demyelination and axonal degeneration occurring in the
      region, suggesting instead a functional neuronal stability. Taken in association
      with the findings of lack of clinical manifestations and the known transient
      nature of T2-weighted hyperintensities in NF1 as demonstrated by other studies,
      our results support the current histopathologically driven hypothesis that such
      T2-weighted hyperintensities may be related to intramyelinic edema.

PMID- 25585913
TI  - Nimodipine for the prevention of cerebral vasospasm after subarachnoid hemorrhage
      in 12 children.
AB  - INTRODUCTION: Subarachnoid hemorrhage is a rare, but life-threatening
      neurological emergency. Cerebral vasospasm is a complication of subarachnoid
      hemorrhage that contributes significantly to morbidity and mortality. Nimodipine
      has been used in adults to reduce the incidence of cerebral vasospasm after
      subarachnoid hemorrhage and improve long-term outcomes. There are, however, no
      data in children. METHODS: Records of children with a confirmed diagnosis of
      subarachnoid hemorrhage who received nimodipine between January 1, 2005 and
      August 31, 2013 were reviewed. Dosing of nimodipine and associated hypotensive
      events were recorded. Transcranial Doppler ultrasonography, cranial computerized
      tomography, and angiography were followed as a measure of cerebral vasospasm,
      rebleeding, and subsequent infarction. RESULTS: Twelve children (average age 11.8
      +/- 3.3 years, age range 3.5 to 17.3 years) were included. Aneurysm was
      responsible for the highest percentage (41.7%) of subarachnoid hemorrhage events.
      The mean dose of oral nimodipine was 1 mg/kg every 4 hours and was associated
      with a high rate of hypotension requiring intervention or dose modification.
      Clinical outcomes while on nimodipine therapy varied; evidence of vasospasm was
      observed in 67%, new infarction in 33%, and rebleeding in 17%. Functional and
      cognitive deficits were minor in two-thirds and absent in the remaining
      individuals. All patients survived until hospital discharge. CONCLUSIONS: Oral
      nimodipine after subarachnoid hemorrhage in children does not eliminate
      vasospasm, rebleeding, or infarction and is associated with significant
      hypotension. Nevertheless, clinical outcomes appear favorable relative to the
      adult population who receive nimodipine. Further study, with dose titration, is
      warranted.

PMID- 25585914
TI  - Development of an engineered soil bacterium enabling to convert both insoluble
      inorganic and organic phosphate into plant available phosphate and its use as a
      biofertilizer.
AB  - Phosphorus (P) is one of the most important nutrient elements for plant growth
      and metabolism. We previously isolated a P-solubilizing bacterium 9320-SD with
      the ability to utilize inorganic P and convert it into plant-available P. The
      present study aims to enhance the P-solubilizing capacity of 9320-SD, as our long
      term goal is to develop a more effective P-solubilizing bacterial strain for use
      as a biofertilizer. In this end, we introduced a bacterial phytase encoding gene
      into 9320-SD. One randomly selected transformant, SDLiuTP02, was examined for
      recombinant protein expression and phytase activity, and assessed for its ability
      to promote plant growth. Our results indicate that SDLiuTP02 is capable of
      expressing high levels of phytase activity. Importantly, corn seedlings treated
      with the SDLiuTP02 cell culture exhibited increased rates of photosynthesis,
      transpiration, and stomatal conductance as well as increased growth rate under
      laboratory conditions and increased growth rate in pot assays compared to
      seedlings treated with cell cultures of the parental strain 9320-SD. Field
      experiments further indicated that application of SDLiuTP02 promoted a greater
      growth rate in young cucumber plant and a higher foliar chlorophyll level in chop
      suey greens when compared to 9320-SD treated controls. These results indicate
      that SDLiuTP02 has the potential to be a more effective P biofertilizer to
      increase agricultural productivity. 

PMID- 25585915
TI  - Spontaneous immortalization of mouse liver sinusoidal endothelial cells.
AB  - The spontaneous immortalization of cells in vitro is a rare event requiring
      genomic instability, such as alterations in chromosomes and mutations in genes.
      In the present study, we report a spontaneously immortalized liver sinusoidal
      endothelial cell (LSEC) line generated from mouse liver. These immortalized LSECs
      showed typical LSEC characteristics with the structure of transcellular
      fenestrations, the expression of von Willebrand factor (VWF) and the ability to
      uptake DiI-acetylated-low density lipoprotein (DiI-Ac-LDL). However, these
      immortalized LSECs lost the ability to form capillary-like structures, and showed
      clonal and multilayer growth without contact inhibition. Moreover, their
      proliferation rate increased with the increase in the number of passages. In
      addition, these cells obained the expression of CD31 and desmin, and showed an
      upregulation of p53 protein expression; however, their karyotype was normal, and
      they could not form colonies in soft agar or tumors in SCID mice. In conclusion,
      in the present study, we successfully established a spontaneously immortalized
      LSEC line.

PMID- 25585916
TI  - A potent tumoricidal co-drug 'Bet-CA'--an ester derivative of betulinic acid and
      dichloroacetate selectively and synergistically kills cancer cells.
AB  - Selective targeting of cancer cells employing multiple combinations as co-drug
      holds promise for new generation therapeutics. Betulinic acid (BA), a plant
      secondary metabolite kills cancer cells and Dichloroacetate (DCA) is capable of
      reversing the Warburg phenotype by inhibiting pyruvate dehydrogenase kinase
      (PDK). Here, we report synthesis, characterization and tumoricidal potential of a
      co-drug Bet-CA, where a DCA molecule has been appended on C-3 hydroxyl group of
      BA to generate an ester derivative for increased solubility and subsequent
      cleavage by internal esterase(s) to release one unit each of BA and DCA. In vitro
      studies revealed pronounced synergistic cytotoxicity of Bet-CA against a broad
      spectrum of cancer cells and it selectively killed them when co-cultured with
      human fibroblasts. Bet-CA treatment increased reactive oxygen species (ROS)
      production, significantly altered mitochondrial membrane potential gradient
      (DeltaPsim); followed by the release of cytochrome c (Cyt c) which prompted cells
      to undergo mitochondria mediated apoptosis. In vivo experimentation expectedly
      exhibited tumor inhibitory potential of Bet-CA and clinically achievable doses
      did not produce any apparent toxicity. Taken together, results suggestively raise
      an important corollary hypothesis stating that Bet-CA selectively and
      synergistically combats cancer without producing toxic manifestations and emerges
      to be the prospect for the new generation therapeutics. 

PMID- 25585917
TI  - Post-relapse survival in patients with Ewing sarcoma.
AB  - BACKGROUND: Post-relapse survival (PRS) was evaluated in patients with Ewing
      sarcoma (EWS) enrolled in chemotherapy protocols based on the use of high-dose
      chemotherapy with busulfan and melfalan (HDT) as a first-line consolidation
      treatment in high-risk patients. PROCEDURE: EWS patients enrolled in ISG/SSG III
      and IV trials who relapsed after complete remission were included in the
      analysis. At recurrence, chemotherapy based on high-dose ifosfamide was foreseen,
      and patients who responded but had not received HDT underwent consolidation
      therapy with HDT. RESULTS: Data from 107 EWS patients were included in the
      analysis. Median time to recurrence (RFI) was 18 months, and 45 (42%) patients
      had multiple sites of recurrence. Patients who had previously been treated with
      HDT had a significantly (P = 0.02) shorter RFI and were less likely to achieve a
      second complete remission (CR2). CR2 status was achieved by 42 (39%) patients.
      Fifty patients received high-dose IFO (20 went to consolidation HDT). The 5-year
      PRS was 19% (95% CI 11 to 27%). With CR2, the 5-year PRS was 48% (95% CI 31 to
      64%). Without CR2, median time to death was six months (range 1-45 months).
      According to the multivariate analysis, patients younger than 15 years,
      recurrence to the lung only, and RFI longer than 24 months significantly
      influenced the probability of PRS. CONCLUSIONS: Age, pattern of recurrence, RFI,
      and response to second-line chemotherapy influence post-relapse survival in
      patients with recurrent Ewing sarcoma. No survival advantage was observed from
      chemotherapy consolidation with HDT.

PMID- 25585918
TI  - Joint-multiple family linkage analysis predicts within-family variation better
      than single-family analysis of the maize nested association mapping population.
AB  - Quantitative trait locus (QTL) mapping has been used to dissect the genetic
      architecture of complex traits and predict phenotypes for marker-assisted
      selection. Many QTL mapping studies in plants have been limited to one biparental
      family population. Joint analysis of multiple biparental families offers an
      alternative approach to QTL mapping with a wider scope of inference. Joint
      multiple population analysis should have higher power to detect QTL shared among
      multiple families, but may have lower power to detect rare QTL. We compared
      prediction ability of single-family and joint-family QTL analysis methods with
      fivefold cross-validation for 6 diverse traits using the maize nested association
      mapping population, which comprises 25 biparental recombinant inbred families.
      Joint-family QTL analysis had higher mean prediction abilities than single-family
      QTL analysis for all traits at most significance thresholds, and was always
      better at more stringent significance thresholds. Most robust QTL (detected in
      >50% of data samples) were restricted to one family and were often not detected
      at high frequency by joint-family analysis, implying substantial genetic
      heterogeneity among families for complex traits in maize. The superior predictive
      ability of joint-family QTL models despite important genetic differences among
      families suggests that joint-family models capture sufficient smaller effect QTL
      that are shared across families to compensate for missing some rare large-effect
      QTL. 

PMID- 25585919
TI  - Sympatric speciation in killer whales?

PMID- 25585920
TI  - Inheritance of thelytoky in the honey bee Apis mellifera capensis.
AB  - Asexual reproduction via thelytokous parthenogenesis is widespread in the
      Hymenoptera, but its genetic underpinnings have been described only twice. In the
      wasp Lysiphlebus fabarum and the Cape honey bee Apis mellifera capensis the
      origin of thelytoky have each been traced to a single recessive locus. In the
      Cape honey bee it has been argued that thelytoky (th) controls the thelytoky
      phenotype and that a deletion of 9 bp in the flanking intron downstream of exon 5
      (tae) of the gemini gene switches parthenogenesis from arrhenotoky to thelytoky.
      To further explore the mode of inheritance of thelytoky, we generated reciprocal
      backcrosses between thelytokous A. m. capensis and the arrhenotokous A. m.
      scutellata. Ten genetic markers were used to identify 108 thelytokously produced
      offspring and 225 arrhenotokously produced offspring from 14 colonies. Patterns
      of appearance of thelytokous parthenogenesis were inconsistent with a single
      locus, either th or tae, controlling thelytoky. We further show that the 9 bp
      deletion is present in the arrhenotokous A. m. scutellata population in South
      Africa, in A. m. intermissa in Morocco and in Africanized bees from Brazil and
      Texas, USA, where thelytoky has not been reported. Thus the 9  p deletion cannot
      be the cause of thelytoky. Further, we found two novel tae alleles. One contains
      the previously described 9 bp deletion and an additional deletion of 7 bp nearby.
      The second carries a single base insertion with respect to the wild type. Our
      data are consistent with the putative th locus increasing reproductive capacity.

PMID- 25585922
TI  - Transcriptome of the quorum-sensing signal-degrading Rhodococcus erythropolis
      responds differentially to virulent and avirulent Pectobacterium atrosepticum.
AB  - Social bacteria use chemical communication to coordinate and synchronize gene
      expression via the quorum-sensing (QS) regulatory pathway. In Pectobacterium, a
      causative agent of the blackleg and soft-rot diseases on potato plants and
      tubers, expression of the virulence factors is collectively controlled by the QS
      signals N-acylhomoserine lactones (NAHLs). Several soil bacteria, such as the
      actinobacterium Rhodococcus erythropolis, are able to degrade NAHLs, hence quench
      the chemical communication and virulence of Pectobacterium. Here, next-generation
      sequencing was used to investigate structural and functional genomics of the NAHL
      degrading R. erythropolis strain R138. The R. erythropolis R138 genome (6.7 Mbp)
      contained a single circular chromosome, one linear (250 kbp) and one circular (84
      kbp) plasmid. Growth of R. erythropolis and P. atrosepticum was not altered in
      mixed-cultures as compared with monocultures on potato tuber slices. HiSeq
      transcriptomics revealed that no R. erythropolis genes were differentially
      expressed when R. erythropolis was cultivated in the presence vs absence of the
      avirulent P. atrosepticum mutant expI, which is defective for QS-signal
      synthesis. By contrast 50 genes (<1% of the R. erythropolis genome) were
      differentially expressed when R. erythropolis was cultivated in the presence vs
      absence of the NAHL-producing virulent P. atrosepticum. Among them, quantitative
      real-time reverse-transcriptase-PCR confirmed that the expression of some alkyl
      sulfatase genes decreased in the presence of a virulent P. atrosepticum, as well
      as deprivation of organic sulfur such as methionine, which is a key precursor in
      the synthesis of NAHL by P. atrosepticum. 

PMID- 25585923
TI  - Quantifying realized inbreeding in wild and captive animal populations.
AB  - Most molecular measures of inbreeding do not measure inbreeding at the scale that
      is most relevant for understanding inbreeding depression-namely the proportion of
      the genome that is identical-by-descent (IBD). The inbreeding coefficient FPed
      obtained from pedigrees is a valuable estimator of IBD, but pedigrees are not
      always available, and cannot capture inbreeding loops that reach back in time
      further than the pedigree. We here propose a molecular approach to quantify the
      realized proportion of the genome that is IBD (propIBD), and we apply this method
      to a wild and a captive population of zebra finches (Taeniopygia guttata). In
      each of 948 wild and 1057 captive individuals we analyzed available single
      nucleotide polymorphism (SNP) data (260 SNPs) spread over four different genomic
      regions in each population. This allowed us to determine whether any of these
      four regions was completely homozygous within an individual, which indicates IBD
      with high confidence. In the highly nomadic wild population, we did not find a
      single case of IBD, implying that inbreeding must be extremely rare (propIBD=0
      0.00094, 95% CI). In the captive population, a five-generation pedigree strongly
      underestimated the average amount of realized inbreeding
      (FPed=0.013<propIBD=0.064), as expected given that pedigree founders were already
      related. We suggest that this SNP-based technique is generally useful for
      quantifying inbreeding at the individual or population level, and we show
      analytically that it can capture inbreeding loops that reach back up to a few
      hundred generations. 

PMID- 25585924
TI  - Persistent organic pollutants and promoter hypermethylation of the O(6)
      methylguanine-DNA methyltransferase gene.
AB  - Promoter hypermethylation of the O(6)-methylguanine-DNA methyltransferase (MGMT)
      DNA repair gene is important during carcinogenesis. We explored whether
      organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), were
      associated with hypermethylation of the MGMT gene promoter in peripheral
      leukocytes among 368 Koreans without cancer. Hypermethylation decreased as OCPs
      increased (Ptrend = 0.02), while PCB concentrations showed an inverted U-shaped
      association (Pquadratic < 0.01). The prevalence of MGMT promoter hypermethylation
      was highest within the 2nd quintile of the PCB summary score (28.4%), while it
      was only 2.7% in the upper 10% score. Chronic exposure to these chemicals may
      affect methylation of the MGMT promoter, with possibly non-monotonic dose
      response relationships. 

PMID- 25585925
TI  - Role of osteoprotegerin in vascular disorders of the end-stage renal disease
      patients.
AB  - AIM: To assess the osteoprotegerin (OPG) relationship with cardiovascular
      complications in hemodialysis (HD) patients. METHODS: The study included 87 HD
      patients. Clinical characteristics, ankle-arm index (AAI), OPG and mineral
      markers levels were recorded. Arterial intimal calcification (AIC) and arterial
      medial calcification (AMC) were registered. RESULTS: OPG levels were increased in
      HD patients. Patients with AIC (p = 0.006)/ AMC (p = 0.01) had higher OPG levels.
      OPG did not have any relation with cardiovascular diseases. OPG correlated
      positively with age, increased HD vintage and inversely with albumin and AAI. OPG
      has not been a risk factor for VC or cardiovascular disease. CONCLUSION: OPG
      rising could be a reaction in defense to vascular aggression, because OPG was
      associated with VC, but not with vascular disease.

PMID- 25585926
TI  - 4-Methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol as a urinary biomarker for
      monitoring of metofluthrin, a fluorine-containing pyrethroid, in exposed rats.
AB  - CONTEXT: A fluorine-containing pyrethroid metofluthrin is widely used recently in
      mosquito repellents. OBJECTIVE: The urinary excretion kinetics of its metabolites
      was evaluated in rats to establish an optimal biomarker for monitoring
      metofluthrin exposure of the general population. METHODS AND RESULTS: After
      metofluthrin had been administered intraperitoneally to rats, the urinary
      excretion kinetics of the major metofluthrin metabolites was evaluated by moment
      analysis. The urinary excretion amounts of 4-methoxymethyl-2,3,5,6
      tetrafluorobenzyl alcohol were estimated to be proportional to the absorption
      amounts over a wide exposure range. CONCLUSION: Urinary 4-methoxymethyl-2,3,5,6
      tetrafluorobenzyl alcohol was considered to be an optimal biomarker for
      metofluthrin exposure.

PMID- 25585927
TI  - Thiol- and biotin-labeled probes for oligonucleotide quartz crystal microbalance
      biosensors of microalga alexandrium minutum.
AB  - Two quartz crystal microbalance oligonucleotide biosensors of a toxic microalga
      gene sequence (Alexandrium Minutum) have been designed. Grafting on a gold
      surface of 20-base thiol- or biotin-labeled probe, and selective hybridization
      with the complementary 20-base target, have been monitored in situ with a 27 MHz
      quartz crystal microbalance under controlled hydrodynamic conditions. The
      frequency of the set up is stable to within a few hertz, corresponding to the
      nanogram scale, for three hour experiments. DNA recognition by the two biosensors
      is efficient and selective. Hybridization kinetic curves indicate that the
      biosensor designed with the thiol-labeled probe is more sensitive, and that the
      biosensor designed with the biotin-labeled probe has a shorter time response and
      a higher hybridization efficiency. 

PMID- 25585928
TI  - Effect of toxic components on microbial fuel cell-polarization curves and
      estimation of the type of toxic inhibition.
AB  - Polarization curves are of paramount importance for the detection of toxic
      components in microbial fuel cell (MFC) based biosensors. In this study,
      polarization curves were made under non-toxic conditions and under toxic
      conditions after the addition of various concentrations of nickel, bentazon,
      sodiumdodecyl sulfate and potassium ferricyanide. The experimental polarization
      curves show that toxic components have an effect on the electrochemically active
      bacteria in the cell. (Extended) Butler Volmer Monod (BVM) models were used to
      describe the polarization curves of the MFC under nontoxic and toxic conditions.
      It was possible to properly fit the (extended) BVM models using linear regression
      techniques to the polarization curves and to distinguish between different types
      of kinetic inhibitions. For each of the toxic components, the value of the
      kinetic inhibition constant Ki was also estimated from the experimental data. The
      value of Ki indicates the sensitivity of the sensor for a specific component and
      thus can be used for the selection of the biosensor for a toxic component. 

PMID- 25585929
TI  - Electrochemical based biosensors.
AB  - This editorial summarizes the general approaches of the electrochemical based
      biosensors described in the manuscripts published in this Special Issue.
      Electrochemical based biosensors are scientifically and economically important
      for the detection and early diagnosis of many diseases, and they will be
      increasing used and developed in the coming years. The importance of the
      selection of recognition processes, fabrication techniques and biosensor
      materials will be introduced. 

PMID- 25585930
TI  - A Comparative Study of Impedance versus Optical Label-Free Systems Relative to
      Labelled Assays in a Predominantly Gi Coupled GPCR (C5aR) Signalling.
AB  - Profiling ligand function on G-protein coupled receptors (GPCRs) typically
      involves using transfected cells over-expressing a target of interest, a labelled
      ligand, and intracellular secondary messenger reporters. In contrast, label-free
      assays are sensitive enough to allow detection in native cells, which may provide
      a more physiologically relevant readout. Here, we compare four agonists (native
      agonists, a peptide full agonist and a peptide partial agonist) that stimulate
      the human inflammatory GPCR C5aR. The receptor was challenged when present in
      human monocyte-derived macrophages (HMDM) versus stably transfected human C5aR
      CHO cells. Receptor activation was compared on label-free optical and impedance
      biosensors and contrasted with results from two traditional reporter assays. The
      rank order of potencies observed across label-free and pathway specific assays
      was similar. However, label-free read outs gave consistently lower potency values
      in both native and transfected cells. Relative to pathway-specific assays, these
      technologies measure whole-cell responses that may encompass multiple signalling
      events, including down-regulatory events, which may explain the potency
      discrepancies observed. These observations have important implications for
      screening compound libraries against GPCR targets and for selecting drug
      candidates for in vivo assays. 

PMID- 25585931
TI  - Biomolecular Interaction Analysis of Gestrinone-anti-Gestrinone Using Arrays of
      High Aspect Ratio SU-8 Nanopillars.
AB  - In this paper, label-free biosensing for antibody screening by periodic lattices
      of high-aspect ratio SU-8 nano-pillars (BICELLs) is presented. As a
      demonstration, the determination of anti-gestrinone antibodies from whole rabbit
      serum is carried out, and for the first time, the dissociation constant (KD = 6
      nM) of antigen-antibody recognition process is calculated using this sensing
      system. After gestrinone antigen immobilization on the BICELLs, the
      immunorecognition was performed. The cells were interrogated vertically by using
      micron spot size Fourier transform visible and IR spectrometry (FT-VIS-IR), and
      the dip wavenumber shift was monitored. The biosensing assay exhibited good
      reproducibility and sensitivity (LOD = 0.75 ng/mL). 

PMID- 25585932
TI  - Functional Conducting Polymers via Thiol-ene Chemistry.
AB  - We demonstrate here that thiol-ene chemistry can be used to provide side-chain
      functionalized monomers based on 3,4-propylenedioxythiophene (ProDOT) containing
      ionic, neutral, hydrophobic, and hydrophilic side chains. All reactions gave high
      yields and purification could generally be accomplished through precipitation.
      These monomers were polymerized either chemically or electro-chemically to give
      soluble materials or conductive films, respectively. This strategy provides for
      facile tuning of the solubility, film surface chemistry, and film morphology of
      this class of conducting polymers. 

PMID- 25585934
TI  - Learning and coordinating in a multilayer network.
AB  - We introduce a two layer network model for social coordination incorporating two
      relevant ingredients: a) different networks of interaction to learn and to obtain
      a pay-off, and b) decision making processes based both on social and strategic
      motivations. Two populations of agents are distributed in two layers with
      intralayer learning processes and playing interlayer a coordination game. We find
      that the skepticism about the wisdom of crowd and the local connectivity are the
      driving forces to accomplish full coordination of the two populations, while
      polarized coordinated layers are only possible for all-to-all interactions. Local
      interactions also allow for full coordination in the socially efficient Pareto
      dominant strategy in spite of being the riskier one. 

PMID- 25585933
TI  - Development of a Fish Cell Biosensor System for Genotoxicity Detection Based on
      DNA Damage-Induced Trans-Activation of p21 Gene Expression.
AB  - p21CIP1/WAF1 is a p53-target gene in response to cellular DNA damage. Here we
      report the development of a fish cell biosensor system for high throughput
      genotoxicity detection of new drugs, by stably integrating two reporter plasmids
      of pGL3-p21-luc (human p21 promoter linked to firefly luciferase) and pRL-CMV-luc
      (CMV promoter linked to Renilla luciferase) into marine flatfish flounder gill
      (FG) cells, referred to as p21FGLuc. Initial validation of this genotoxicity
      biosensor system showed that p21FGLuc cells had a wild-type p53 signaling pathway
      and responded positively to the challenge of both directly acting genotoxic
      agents (bleomycin and mitomycin C) and indirectly acting genotoxic agents
      (cyclophosphamide with metabolic activation), but negatively to cyclophosphamide
      without metabolic activation and the non-genotoxic agents ethanol and D-mannitol,
      thus confirming a high specificity and sensitivity, fast and stable response to
      genotoxic agents for this easily maintained fish cell biosensor system. This
      system was especially useful in the genotoxicity detection of Di(2-ethylhexyl)
      phthalate (DEHP), a rodent carcinogen, but negatively reported in most non
      mammalian in vitro mutation assays, by providing a strong indication of
      genotoxicity for DEHP. A limitation for this biosensor system was that it might
      give false positive results in response to sodium butyrate and any other agents,
      which can trans-activate the p21 gene in a p53-independent manner. 

PMID- 25585935
TI  - A 3D nanofibrous hydrogel and collagen sponge scaffold promotes locomotor
      functional recovery, spinal repair, and neuronal regeneration after complete
      transection of the spinal cord in adult rats.
AB  - Central nervous system neurons in adult mammals display limited regeneration
      after injury, and functional recovery is poor following complete transection (>4
      mm gap) of a rat spinal cord. A novel combination scaffold composed of 3D
      nanofibrous hydrogel PuraMatrix and a honeycomb collagen sponge was used to
      promote spinal repair and locomotor functional recovery following complete
      transection of the spinal cord in rats. We transplanted this scaffold into 5 mm
      spinal cord gaps and assessed spinal repair and functional recovery using the
      Basso, Beattie, and Bresnahan (BBB) locomotor scale. The BBB score of the
      scaffold-transplanted group was significantly higher than that of the PBS
      injected control group from 24 d to 4 months after the operation (P < 0.001
      0.01), reaching 6.0  +/-  0.75 (mean +/- SEM) in the transplant and 0.70  +/- 
      0.46 in the control groups. Neuronal regeneration and spinal repair were examined
      histologically using Pan Neuronal Marker, glial fibrillary acidic protein, growth
      associated protein 43, and DAPI. The scaffolds were well integrated into the
      spinal cords, filling the 5 mm gaps with higher numbers of regenerated and
      migrated neurons, astrocytes, and other cells than in the control group. Mature
      and immature neurons and astrocytes in the scaffolds became colocalized and
      aligned longitudinally over >2 mm, suggesting their differentiation, maturation,
      and function. The spinal cord NF200 content of the transplant group, analyzed by
      western blot, was more than twice that of the control group, supporting the
      histological results. Transplantation of this novel scaffold promoted functional
      recovery, spinal repair, and neuronal regeneration. 

PMID- 25585921
TI  - Geographical barriers and climate influence demographic history in narrowleaf
      cottonwoods.
AB  - Studies of genetic variation can clarify the role of geography and spatio
      temporal variation of climate in shaping demography, particularly in temperate
      zone tree species with large latitudinal ranges. Here, we examined genetic
      variation in narrowleaf cottonwood, Populus angustifolia, a dominant riparian
      tree. Using multi-locus surveys of polymorphism in 363 individuals across the
      species' 1800 km latitudinal range, we found that, first, P. angustifolia has
      stronger neutral genetic structure than many forest trees (simple sequence repeat
      (SSR) FST=0.21), with major genetic groups corresponding to large apparent
      geographical barriers to gene flow. Second, using SSRs and putatively neutral
      sequenced loci, coalescent simulations indicated that populations diverged before
      the last glacial maximum (LGM), suggesting the presence of population structure
      before the LGM. Third, the LGM and subsequent warming appear to have had
      different influences on each of these distinct populations, with effective
      population size reduction in the southern extent of the range but major expansion
      in the north. These results are consistent with the hypothesis that climate and
      geographic barriers have jointly affected the demographic history of P.
      angustifolia, and point the importance of both factors as being instrumental in
      shaping genetic variation and structure in widespread forest trees. 

PMID- 25585937
TI  - Highly efficient spin-conversion effect leading to energy up-converted
      electroluminescence in singlet fission photovoltaics.
AB  - Free charge generation in donor-acceptor (D-A) based organic photovoltaic diodes
      (OPV) progresses through formation of charge-transfer (CT) and charge-separated
      (CS) states and excitation decay to the triplet level is considered as a terminal
      loss. On the other hand a direct excitation decay to the triplet state is
      beneficial for multiexciton harvesting in singlet fission photovoltaics (SF-PV)
      and the formation of CT-state is considered as a limiting factor for multiple
      triplet harvesting. These two extremes when present in a D-A system are expected
      to provide important insights into the mechanism of free charge generation and
      spin-character of bimolecular recombination in OPVs. Herein, we present the
      complete cycle of events linked to spin conversion in the model OPV system of
      rubrene/C60. By tracking the spectral evolution of photocurrent generation at
      short-circuit and close to open-circuit conditions we are able to capture
      spectral changes to photocurrent that reveal the triplet character of CT-state.
      Furthermore, we unveil an energy up-conversion effect that sets in as a
      consequence of triplet population build-up where triplet-triplet annihilation
      (TTA) process effectively regenerates the singlet excitation. This detailed
      balance is shown to enable a rare event of photon emission just above the open
      circuit voltage (V(OC)) in OPVs.

PMID- 25585936
TI  - Early development of human lymphomas in a prostate cancer xenograft program using
      triple knock-out immunocompromised mice.
AB  - BACKGROUND: There is an urgent need for preclinical models of prostate cancer;
      however, clinically relevant patient-derived prostate cancer xenografts (PDXs)
      are demanding to establish. METHODS: Sixty-seven patients who were undergoing
      palliative transurethral surgery or radical prostatectomy for histologically
      confirmed, clinically relevant prostate cancer were included in the study. Fresh
      prostate cancer tissue was identified by frozen analysis in 48 patients. The
      cancer tissue was transplanted subcutaneously and under the renal capsule of NSG
      and NOG mice supplemented with human testosterone. All growing PDXs were
      evaluated by histology and immunohistochemistry. RESULTS: Early assessment of the
      animals at least three months after transplantation included 27/48 (56.3%)
      eligible PDX cohorts. PDX growth was detected in 10/27 (37%) mouse cohorts. Eight
      of the ten PDXs were identified as human donor derived lymphomas, including seven
      Epstein Barr virus (EBV)-positive diffuse large B-cell lymphomas and one EBV
      negative peripheral T-cell lymphoma. One sample consisted of benign prostatic
      tissue, and one sample comprised a benign epithelial cyst. Prostate cancer was
      not detected in any of the samples. CONCLUSIONS: Tumors that arise within the
      first three months after prostate cancer xenografting may represent patient
      derived EBV-positive lymphomas in up to 80% of the early growing PDXs when using
      triple knockout NSG immunocompromised mice. Therefore, lymphoma should be
      excluded in prostate cancer xenografts that do not resemble typical prostatic
      adenocarcinoma.

PMID- 25585940
TI  - Planar pentacoordinate carbons in CBe5(4-) derivatives.
AB  - The potential energy surfaces of a series of clusters with formula CBe5Lin(n-4)
      (n = 1 to 5) have been systematically explored. Our computations show that the
      lithium cations preserve the CBe5(4-) pentagon, such that the global minimum
      structure for these series of clusters has a planar pentacoordinate carbon (ppC)
      atom. The systems are primarily connected via a network of multicenter sigma
      bonds, in which the C atom acts as sigma-acceptor and this acceptance of charge
      is balanced by the donation of the 2pz electrons to the pi-cloud. The induced
      magnetic field analysis suggests that the clusters with formula CBe5Lin(n-4) (n =
      1 to 5) are fully delocalized. The fact that these ppC-containing clusters are
      the lowest-energy forms on the corresponding potential energy surfaces raises
      expectations that these species can be prepared experimentally in the gas phase.

PMID- 25585938
TI  - Rhodium(III)-catalyzed C-H activation and intermolecular annulation with terminal
      alkynes: from indoles to carbazoles.
AB  - Herein we disclose the first example of Rh(iii)-catalyzed intermolecular
      annulation of indoles with terminal alkynes to give highly efficient one-pot
      access to privileged carbazoles. The mild reaction features moderate to good
      yields, exclusive regioselectivity, broad substrate scope, and excellent
      functional group tolerance. 

PMID- 25585941
TI  - MiR-221-induced PUMA silencing mediates immune evasion of bladder cancer cells.
AB  - Immune evasion of cancer cells is mainly due to the impaired transduction of
      apoptotic signals from immune cells to cancer cells, as well as inhibition of
      subsequent apoptosis signal cascades within the cancer cells. Over the past few
      decades, the research has focused more on the impaired transduction of the
      apoptotic signal from immune cells to cancer cells, rather than inhibition of the
      intracellular signaling pathways. In this study, miR-221 inhibitor was
      transfected into bladder cancer cell lines 5637, J82 and T24 to repress the
      expression of miR-221. As a result, the repression of miR-221 on p53 upregulated
      modulator of apoptosis (PUMA) was abolished, resulting in increased expression of
      the pro-apoptotic Bax and reduced expression of the anti-apoptotic Bcl-2, which
      promotes apoptosis of bladder cancer cells. The expression of MMP-2, MMP-9 and
      VEGF-C were reduced, resulting in reduced invasiveness and infiltration
      capability of bladder cancer cells, thereby inhibiting the immune evasion of
      bladder cancer cells. 

PMID- 25585943
TI  - Six years and counting.

PMID- 25585942
TI  - Improving efficiency in clinical trials using auxiliary information: Application
      of a multi-state cure model.
AB  - In clinical trials, an intermediate marker measured after randomization can often
      provide early information about the treatment effect on the final outcome of
      interest. We explore the use of recurrence time as an auxiliary variable for
      estimating the treatment effect on overall survival in phase three randomized
      trials of colon cancer. A multi-state model with an incorporated cured fraction
      for recurrence is used to jointly model time to recurrence and time to death. We
      explore different ways in which the information about recurrence time and the
      assumptions in the model can lead to improved efficiency. Estimates of overall
      survival and disease-free survival can be derived directly from the model with
      efficiency gains obtained as compared to Kaplan-Meier estimates. Alternatively,
      efficiency gains can be achieved by using the model in a weaker way in a multiple
      imputation procedure, which imputes death times for censored subjects. By using
      the joint model, recurrence is used as an auxiliary variable in predicting
      survival times. We demonstrate the potential use of the proposed methods in
      shortening the length of a trial and reducing sample sizes. 

PMID- 25585944
TI  - Embryonic critical windows: changes in incubation temperature alter survival,
      hatchling phenotype, and cost of development in lake whitefish (Coregonus
      clupeaformis).
AB  - The timing, success and energetics of fish embryonic development are strongly
      influenced by temperature. However, it is unclear if there are developmental
      periods, or critical windows, when oxygen use, survival and hatchling phenotypic
      characteristics are particularly influenced by changes in the thermal
      environment. Therefore, we examined the effects of constant incubation
      temperature and thermal shifts on survival, hatchling phenotype, and cost of
      development in lake whitefish (Coregonus clupeaformis) embryos. We incubated
      whitefish embryos at control temperatures of 2, 5, or 8  degrees C, and shifted
      embryos across these three temperatures at the end of gastrulation or
      organogenesis. We assessed hatch timing, mass at hatch, and yolk conversion
      efficiency (YCE). We determined cost of development, the amount of oxygen
      required to build a unit of mass, for the periods from fertilization
      organogenesis, organogenesis-fin flutter, fin flutter-hatch, and for total
      development. An increase in incubation temperature decreased time to 50 % hatch
      (164 days at 2  degrees C, 104 days at 5  degrees C, and 63 days at 8  degrees
      C), survival decreased from 55 % at 2  degrees C, to 38 % at 5  degrees C, and 17
      % at 8  degrees C, and hatchling yolk-free dry mass decreased from 1.27 mg at 2 
      degrees C to 0.61 mg at 8  degrees C. Thermal shifts altered time to 50 % hatch
      and hatchling yolk-free dry mass and revealed a critical window during
      gastrulation in which a temperature change reduced survival. YCE decreased and
      cost of development increased with increased incubation temperature, but embryos
      that hatched at 8  degrees C and were incubated at colder temperatures during
      fertilization-organogenesis had reduced cost. The relationship between cost of
      development and temperature was altered during fin flutter-hatch, indicating it
      may be a critical window during which temperature has the greatest impact on
      energetic processes. The increase in cost of development with an increase in
      temperature has not been documented in other fishes and suggests whitefish
      embryos are more energy efficient at colder temperatures.

PMID- 25585947
TI  - Association of endothelial nitric oxide synthase gene polymorphism with the risk
      of Henoch-Schonlein purpura/Henoch-Schonlein purpura nephritis.
AB  - Association between endothelial nitric oxide synthase (eNOS) gene polymorphism
      and Henoch-Schonlein purpura (HSP)/Henoch-Schonlein purpura nephritis (HSPN) risk
      is still controversial. A meta-analysis was performed to evaluate the association
      between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined
      literature search and selection of eligible relevant studies were performed to
      collect data from electronic database. Three articles were identified for the
      analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS
      G894T gene polymorphism was not associated with HSPN susceptibility and the risk
      of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and
      GG genotype were associated with HSP susceptibility, but not the TT genotype.
      eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele
      and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated
      with HSP risk and the risk of patients with HSP developing into HSPN. In
      conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele
      and GG genotype were associated with HSP susceptibility. However, more studies
      should be performed in the future.

PMID- 25585945
TI  - Phenotypic flexibility of skeletal muscle and heart masses and expression of
      myostatin and tolloid-like proteinases in migrating passerine birds.
AB  - Migrant birds require large flight muscles and hearts to enhance aerobic capacity
      and support sustained flight. A potential mechanism for increasing muscle and
      heart masses during migration in birds is the muscle growth inhibitor myostatin
      and its metalloproteinase activators, tolloid-like proteinases (TLL-1 and TLL-2).
      We hypothesized that myostatin, TLL-1 and TLL-2 are downregulated during
      migration in pectoralis and hearts of migratory passerines to promote
      hypertrophy. We measured seasonal variation of tissue masses, mRNA expression of
      myostatin, TLL-1, and TLL-2, and myostatin protein levels in pectoralis muscle
      and heart for yellow warblers (Setophaga petechia), warbling vireos (Vireo
      gilvus), and yellow-rumped warblers (Setophaga coronata). Pectoralis mass was
      greatest in spring for warbling vireos and yellow warblers, but was stable
      between spring and fall for yellow-rumped warblers. Heart mass was higher in
      spring than in fall for yellow-rumped warblers, lowest in fall for warbling
      vireos, and seasonally stable for yellow warblers. Pectoralis and heart mRNA
      expression of myostatin and the TLLs did not differ significantly for any of the
      three species, offering little support for our hypothesis for a prominent role
      for myostatin in regulating migration-induced variation in pectoralis and heart
      masses. In contrast, pectoralis myostatin protein levels were lowest in spring
      for all three species, consistent with our hypothesis. Myostatin protein levels
      in heart, however, were seasonally stable for warbling vireos and yellow
      warblers, and increased in spring relative to fall for yellow-rumped warblers.
      These data offer mixed support for our hypothesis for the pectoralis, but suggest
      that myostatin is not a prominent regulator of migration-induced heart
      hypertrophy. Moreover, the different seasonal patterns for pectoralis mRNA and
      protein expression suggest that post-transcriptional modification of myostatin
      may contribute to pectoralis mass regulation during migration. 

PMID- 25585948
TI  - Association of angiotensin II type-1 receptor A1166C gene polymorphism with the
      susceptibility of immunoglobulin A nephropathy.
AB  - Association of angiotensin II type-1 receptor (AT1R) A1166C gene polymorphism
      with the susceptibility of immunoglobulin A nephropathy (IgAN) is still
      controversial. This meta-analysis was conducted to evaluate the association of
      AT1R A1166C gene polymorphism with IgAN susceptibility. The search was performed
      in the databases of PubMed, Embase, and Cochrane Library as of 1 May 2014. The
      eligible investigations were recruited for this meta-analysis. Four literatures
      on the association between AT1R A1166C gene polymorphism and IgAN susceptibility
      were identified for this meta-analysis. Interestingly, all the included studies
      were from Asian population. There was no association between AT1R A1166C gene
      polymorphism and IgAN susceptibility for overall populations (C allele vs. A
      allele: OR = 1.04, 95% CI: 0.78-1.39, p = 0.76; CC vs. AC + AA: OR = 1.20, 95%
      CI: 0.48-2.98, p = 0.70; AA vs. AC + CC: OR = 0.97, 95% CI: 0.70-1.34, p = 0.85),
      and in Asians. In conclusion, AT1R A1166C gene polymorphism was not associated
      with IgAN susceptibility in Asian population. However, more case-control
      association investigations on larger, stratified populations are required in the
      future.

PMID- 25585946
TI  - miR-126 inhibits cell proliferation and induces cell apoptosis of hepatocellular
      carcinoma cells partially by targeting Sox2.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third
      leading cause of cancer-related death globally. MicroRNAs (miRNAs) represent a
      new cohort of gene regulators. Currently, a large number of miRNAs have been
      reported to be associated with the initiation and maintenance of HCC. Through
      evaluating the relative concentrations of HCC-associated circulating miRNAs,
      underexpression of miR-126 has been identified in the blood of HCC patients.
      However, the exact function of miR-126 on HCC cellular biology progression and
      relative mechanisms were unclear. In this paper, we explored the function of miR
      126 on HCC cells through exogenously transfecting HCC cells with miR-126 mimic.
      Restored miR-126 expression inhibited cell proliferation, arrest cell cycle
      progression, and induced cell apoptosis of HepG2 HCC cells. Moreover, to explore
      the mechanism of miR-126-mediated tumor suppression, we searched the putative
      targets of miR-126 using prediction program. Surprisingly, we found that sex
      determining region Y-box 2 (Sox2) was a putative target gene of miR-126. Further
      luciferase assays, mRNA and protein assays consistently validated the target role
      of Sox2. Through restoring the expression of Sox2 in miR-126-transfected HepG2
      cells, we found that overexpression of Sox2 could partially abrogate the miR-126
      mediated suppression of cell growth. Thus, our data identified miR-126 as a tumor
      suppressor in HCC through, at least partially by targeting Sox2. This may provide
      novel diagnostic and therapeutic options for human HCC in future. 

PMID- 25585950
TI  - Is there an association of hepatitis B virus infection with minimal change
      disease of nephrotic syndrome? A clinical observational report.
AB  - The rate of hepatitis B virus (HBV) infection is high in the Chinese population,
      and the implications of HBV infection are widely recognized, and membranous
      nephropathy is the most common renal lesion to be associated with HBV infection.
      Minimal change disease (MCD) is one of the most important histopathological
      characteristics in patients with nephrotic syndrome. There is no any study to
      report that HBV infection is associated with the etiology of MCD. Herein, we
      report four MCD patients with HBV infection and speculate that there is an
      association of HBV infection with the pathological type of MCD. In this study, we
      also reported the treatment schedule for these four MCD patients, and found that
      the anti-virus alone and combination of anti-virus with immunosuppressive agent
      could obtain a benefit for MCD patients with HBV infection. However, a well
      designed study should be performed to confirm this association.

PMID- 25585951
TI  - Factors affecting eGFR 5-year post-deceased donor renal transplant: analysis and
      predictive model.
AB  - AIM: Long-term survival of renal allografts has improved over the last 20 years.
      However, less is known about current expectations for long-term allograft
      function as determined by estimated glomerular filtration rate (eGFR). The aim of
      this study was to investigate factors which affect graft function at 5 years'
      post-renal transplantation. The statistically significant factors were then used
      to construct a predictive model for expected eGFR at five years' post-transplant.
      METHODS: We retrospectively reviewed all adult patients who received a renal
      transplant in the Republic of Ireland between 1990 and 2004. Data collected
      included era of transplantation (1990-1994, 1995-1999, 2000-2004), donor and
      recipient age and gender, number of human leucocyte antigen mismatches, cold
      ischemia time (CIT), number of prior renal transplants, immunosuppressive regimen
      used and acute rejection episodes. Estimated GFR was calculated at 5 years after
      transplantation from patient data using the Modified Diet in Renal Disease (MDRD)
      equation. Consecutive sampling was used to divide the study population into two
      equal unbiased groups of 489 patients. The first group (derivation cohort) was
      used to construct a predictive model for eGFR five years' post-transplantation,
      the second (validation cohort) to test this model. RESULTS: Nine hundred and
      seventy eight patients were analyzed. The median age at transplantation was 43
      years (range 18-78) and 620 (63.4%) were male. One hundred and seventy five
      patients (17.9%) had received a prior renal transplant. Improved eGFR at five
      years' post-transplantation was associated with tacrolimus-based combination
      immunosuppression, younger donor age, male recipient, absence of cytomegalovirus
      disease and absence of acute rejection episodes as independently significant
      factors (p < 0.05). The predictive model developed using these factors showed
      good correlation between predicted and actual median eGFR at five years. The
      model explained 20% of eGFR variability. The validation model findings were
      consistent with the derivation model (21% variability of eGFR explained by model
      using same covariates on new data). CONCLUSION: The predictive model we have
      developed shows good correlation between predicted and actual median eGFR at five
      years' post-transplant. Applications of this model include comparison of current
      and future therapy options such as new immunosuppressive regimens.

PMID- 25585949
TI  - Combination of biomarkers for diagnosis of acute kidney injury after
      cardiopulmonary bypass.
AB  - Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and
      risk stratification, but have yet to find widespread clinical application. We
      measured urinary alpha and pi glutathione S-transferases (alpha-GST and pi-GST),
      urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase
      associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before
      surgery, post-operatively and at 24 h after surgery in 93 high risk patient
      undergoing cardiopulmonary bypass (CPB) and assessed the ability of these
      biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5
      post-operative days. Twenty-five patients developed AKI. pi-GST (ROCAUC = 0.75),
      lower urine Hepcidin:Creatine ratio at 24 h (0.77), greater urine NGAL:Cr ratio
      post-op (0.73) and greater serum CysC at 24 h (0.72) best predicted AKI. Linear
      combinations with significant improvement in AUC were: Hepcidin:Cr 24 h + post
      operative pi-GST (AUC = 0.86, p = 0.01), Hepcidin:Cr 24 h + NGAL:Cr post-op
      (0.84, p = 0.03) and CysC 24 h + post-operative pi-GST (0.83, p = 0.03), notably
      these significant biomarkers combinations all involved a tubular injury and a
      glomerular filtration biomarker. Despite statistical significance in receiver
      operator characteristic (ROC) analysis, when assessed by ability to define
      patients to two groups at high and low risk of AKI, combinations failed to
      significantly improve classification of risk compared to the best single
      biomarkers. In an alternative approach using Classification and Regression Tree
      (CART) analysis a model involving NGAL:Cr measurement post-op followed by
      Hepcidin:Cr at 24 h was developed which identified high, intermediate and low
      risk groups for AKI. Regression tree analysis has the potential produce models
      with greater clinical utility than single combined scores.

PMID- 25585952
TI  - Pseudoexfoliation syndrome in chronic kidney disease patients.
AB  - This study was performed to determine whether chronic kidney disease (CKD) is
      associated with an increased risk of pseudoexfoliation (PEX) syndrome. This is an
      age-matched case control study evaluating frequency of PEX in patients over age
      40 with the diagnosis of stage 1-4 CKD and those undergoing hemodialysis (HD).
      Subjects over age 40 with hypertension and/or diabetes mellitus (DM) and normal
      kidney functions were studied as a control group. CKD was diagnosed as decreased
      glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m(2) for at least 3
      months. Study groups were arranged as group 1 consisting of HD receiving CKD
      patients, group 2 consisting of CKD patients who do not need HD and group 3 as a
      control. Demographic properties and the prevalence of PEX were evaluated and
      compared between groups. Because of the effect of DM on PEX occurrence, it was
      also evaluated after exclusion of diabetic patients. A total of 101 cases in
      group 1, 106 cases in group 2 and 117 cases in group 3 were included in the
      study. Pseudoexfoliation was found in 7 (6.9%) patients in group 1, 5 (4.7%)
      patients in group 2 and 7 (5.9%) patients in group 3 (p > 0.05). After exclusion
      of diabetic patients the prevalence of PEX changed as 4 (5.6%) in group 1, 2
      (4.4%) in group 2 and 1 (1.8%) in group 3 (p > 0.05). In conclusion, CKD was not
      associated with increased prevalence of PEX in this study.

PMID- 25585953
TI  - Effects of vitamin E-coated dialysis membranes on anemia, nutrition and
      dyslipidemia status in hemodialysis patients: a meta-analysis.
AB  - BACKGROUND: This was controversial whether vitamin E-coated dialyzer therapy was
      beneficial for the complications associated with hemodialysis. Therefore, we
      performed this systematic review to evaluate the effects of vitamin E-coated
      dialyzer. METHODS: Related trials were searched from multiple electronic
      databases. We conducted meta-analysis to assess changes in the predefined
      outcomes using RevMan 5.3 software. RESULTS: Meta-analysis showed vitamin E
      coated dialyzer therapy could decrease erythropoietin (EPO) resistance index
      (SMD, -0.24; 95% CI, -0.47 to -0.01; p = 0.04). However, pooled-analysis showed
      vitamin E-coated dialyzer therapy could not decrease weekly EPO dose (SMD, -0.11;
      95% CI, -0.32 to 0.09; p = 0.28) and intima-media thickness (IMT) of the carotid
      artery (MD, -0.09; 95% CI, -0.2 to 0.01; p = 0.09), and vitamin E-coated dialyzer
      therapy did not improve the serum hemoglobin (MD, -0.03; 95% CI, -0.18 to 0.13; p
      = 0.74), albumin levels (SMD, -0.64; 95% CI, -1.62 to 0.34; p = 0.2), in
      addition, there was no significant difference in serum cholesterol (SMD, -0.07;
      95% CI, -0.45 to 0.31; p = 0.71), triglycerides (MD, -2.77; 95% CI, -32.42 to
      26.87; p = 0.85), high density lipoprotein (HDL) (SMD, 0.24; 95% CI, -0.14 to
      0.62; p = 0.22) and low density lipoprotein (LDL) (SMD, 0.00; 95% CI, -0.38 to
      0.37; p = 0.98) levels. CONCLUSIONS: Vitamin E-coated dialyzer may reduce the EPO
      resistance, but there is no conclusive evidence that vitamin E-coated dialyzer
      can improve the renal anemia, malnutrition, dyslipidemia and atherosclerosis
      status in hemodialysis (HD) patients. However, high-quality trials with hard
      clinical endpoints are required to fully elucidate the clinical value of vitamin
      E-coated dialyzer therapy.

PMID- 25585954
TI  - Quality and safety requirements for sustainable phage therapy products.
AB  - The worldwide antibiotic crisis has led to a renewed interest in phage therapy.
      Since time immemorial phages control bacterial populations on Earth. Potent lytic
      phages against bacterial pathogens can be isolated from the environment or
      selected from a collection in a matter of days. In addition, phages have the
      capacity to rapidly overcome bacterial resistances, which will inevitably emerge.
      To maximally exploit these advantage phages have over conventional drugs such as
      antibiotics, it is important that sustainable phage products are not submitted to
      the conventional long medicinal product development and licensing pathway. There
      is a need for an adapted framework, including realistic production and quality
      and safety requirements, that allows a timely supplying of phage therapy products
      for 'personalized therapy' or for public health or medical emergencies. This
      paper enumerates all phage therapy product related quality and safety risks known
      to the authors, as well as the tests that can be performed to minimize these
      risks, only to the extent needed to protect the patients and to allow and advance
      responsible phage therapy and research.

PMID- 25585955
TI  - Microcosmic mechanism of dication for inhibiting acylation of acidic Peptide.
AB  - PURPOSE: For long-effective peptide formulation based on poly(D,L-lactic-co
      glycolic acid) (PLGA) microspheres, acylation often leads to peptide instability
      during its release and reduced drug efficacy. Among the reported solving
      strategies, adding dication such as Ca(2+) and Mn(2+) in the formulation was the
      most convenient method for inhibiting basic peptide acylation. However, the
      strategies for the acidic peptide still remain unexplored, possibly due to the
      peptide's changeable charge state in acid environment within degraded PLGA
      microspheres. Moreover, the previous studies mainly focusing on the macroscopical
      adsorption of peptide to PLGA cannot demonstrate the inhibition mechanism.
      METHODS: Acylation inhibition for acidic peptide (exenatide) by dications
      (Ca(2+), Mn(2+) and Zn(2+)) was studied for the first time, and Quartz Crystal
      Microbalance with Dissipation (QCM-D) was innovatively employed to analyze
      microcosmic mechanism of the inhibition. RESULTS: These dications played
      different roles in acylation inhibition of acidic peptide. The effects of
      dications on acylation outside or inside PLGA microspheres indicated that Ca(2+)
      did not work, Mn(2+) played a weak role, and Zn(2+) possessed the greatest
      inhibition. CONCLUSIONS: Zn(2+) was the most effective dication for the acylation
      inhibition because of the complex formation and its steric-hindrance effect,
      which was a new function for this dication.

PMID- 25585956
TI  - Enhanced Anti-Angiogenic Effect of Low Molecular Weight Heparin-Bile Acid
      Conjugates by Co-Administration of a Selective COX-2 Inhibitor.
AB  - PURPOSE: To overcome definite limitations of angiogenesis inhibitors such as
      insufficient therapeutic efficacy as a single drug and resisting or conflicting
      effect under chronic treatment, it is required to develop a new regimen to
      improve the therapeutic effect. METHODS: The combination effect of a multi
      targeting angiogenesis inhibitor (LHT7) and a selective cyclooxygenase-2
      inhibitor (celecoxib) on neovascularization in tumor growth was studied both in
      vitro and vivo experiments. RESULTS: While hypoxia-mediated COX-2 overexpression
      and macrophage recruitment were observed at LHT7-treated tumor tissues, it was
      well-controlled by the combination of celecoxib and LHT7. On the other hand, the
      in vitro tube formation and the in vivo tumor vessel formation and structure were
      inhibited by either LHT7 or celecoxib, but the inhibition effect was further
      enhanced by using them together. However, the combination therapy did not further
      enhance the inhibitory effect on tumor growth in terms of volume compared to
      single drug uses, which attributed not to increased cellular apoptosis but to
      decreased cell proliferation. CONCLUSIONS: COX-2 inhibition could enhance the
      therapeutic effect of anti-angiogenic drugs both by inhibiting the inflammatory
      reactions induced by hypoxia and by altering the vascular stabilization that is
      mediated by an assembly with mural cells.

PMID- 25585958
TI  - Interaction of aflatoxin B1 and fumonisin B1 in mice causes immunotoxicity and
      oxidative stress: Possible protective role using lactic acid bacteria.
AB  - Aflatoxins (AF) are important foodborne mycotoxins implicated in human health and
      have immunocytotoxic effects. The aims of this study were to evaluate a new
      aflatoxin B1 (AFB1) and fumonisin B1 (FB1)-binding/degrading micro-organism for
      biological detoxification, to examine its ability to degrade AFB1 and FB1 in
      liquid medium, and to evaluate its potential in vivo protective role against any
      combined effects from AFB1 and FB1 on host splenocyte caspase-3 activity
      (reflecting DNA damage/cell death) and mRNA levels of select inflammation
      regulating cytokines. Balb/c mice were divided into groups (10/group) and treated
      daily for 2 weeks by oral gavage with AFB1 (80 ug/kg BW), FB1 (100 ug/kg), AFB1 +
      FB1, or lactic acid bacteria (Lactobacillus paracasei BEJ01, 2 * 10(9) CFU/L, ~2
      mg/kg) - alone or in combination with the AFB1 and/or FB1. After the exposures,
      spleens were collected for measures of caspase-3 activity, lipid peroxidation
      (LP), and glutathione (GSH) content, expression of anti-oxidation protective
      enzymes (GPx and SOD), and mRNA levels of inflammation-regulating cytokines (e.g.
      IL-10, IL-4, IFNgamma, TNFalpha). Thymii were also removed for analysis of
      apoptosis. The results indicated that, in the spleen, exposure to the mycotoxins
      led to increased caspase-3 activity, LP, and IL-10 and IL-4 mRNA levels, but
      decreased GSH content and down-regulated expression of GPx and SOD, and of
      IFNgamma and TNFalpha mRNA. Co-treatment using Lactic Acid Bacteria (LAB) with
      AFB1 or FB1 suppressed levels of DNA fragmentation, normalized splenic LP and
      increased GSH levels, up-regulated expression of GPx and SOD, and normalized mRNA
      levels of the analyzed cytokines. It is concluded that AFB1 and FB1 might have
      combinational (synergistic moreso than additive) toxic effects in situ. Further,
      it can be seen that use of LAB induced protective effects against the oxidative
      stress and (immuno)toxicity of these agents in part through adhesion (and so
      likely diminished bioavalability). 

PMID- 25585957
TI  - Evolving Strategies for Target Selection for Antibody-Drug Conjugates.
AB  - Antibody-drug conjugates (ADCs) represent a promising modality for the treatment
      of cancer. The therapeutic strategy is to deliver a potent drug preferentially to
      the tumor and not normal tissues by attaching the drug to an antibody that
      recognizes a tumor antigen. The selection of antigen targets is critical to
      enabling a therapeutic window for the ADC and has proven to be surprisingly
      complex. We surveyed the tumor and normal tissue expression profiles of the
      targets of ADCs currently in clinical development. Our analysis demonstrates a
      surprisingly broad range of expression profiles and the inability to formalize
      any optimal parameters for an ADC target. In this context, we discuss additional
      considerations for ADC target selection, including interdependencies among
      biophysical properties of the drug, biological functions of the target and
      strategies for clinical development. The TPBG (5T4) oncofetal antigen and the
      anti-TPBG ADC A1-mcMMAF are highlighted to demonstrate the relevance of the
      target's biological function. Emerging platform technologies and novel biological
      insights are expanding ADC target space and transforming strategies for target
      selection. 

PMID- 25585959
TI  - Fully human anti-BAFF inhibitory monoclonal antibody tabalumab does not adversely
      affect T-dependent antibody responses in cynomolgus monkey (Macaca fasicularis):
      A summary of three pre-clinical immunotoxicology evaluations.
AB  - The potential immunotoxicity of tabalumab was assessed as a component of standard
      pre-clinical toxicology studies in cynomolgus monkeys. To evaluate potential
      tabalumab-associated immunosuppression after antigen challenge, cynomolgus
      monkeys were administered placebo control or tabalumab in three
      immunotoxicological safety studies. Study 1, a 4-week pilot study, evaluated
      biweekly intravenous (IV) control, and 0.3, 1.0, 5.0, and 15.0 mg/kg tabalumab
      doses. Study 2 evaluated IV control, and 0.1, 1.0, and 30.0 mg/kg tabalumab doses
      biweekly for 6 weeks. Study 3 evaluated IV control and 0.1, 1.0, 30.0 mg/kg, and
      subcutaneous (SC) 30.0 mg/kg tabalumab biweekly for 6 months, with recovery (16
      weeks) to monitor standard immunotoxicity endpoints. T-cell dependent primary and
      secondary antibody responses to tetanus toxoid antigen challenge (4-week and 6
      week studies) or keyhole limpet hemocyanin (KLH; 6-week and 6-month studies) were
      evaluated as a measure of immunocompetence, together with quantitation of T- and
      B-cell subsets. In addition, anti-tabalumab antibody formation (6-week and 6
      month studies) was assessed. The results indicated that, despite expected
      decreases in circulating B-cell populations, no changes in follicle
      histopathology or organ weights, except decreases in spleen weight (after 6
      months of 30 mg/kg IV/SC treatment only), were attributed to tabalumab. Non
      adverse microscopic decreases in size or number of germinal centers in spleen,
      mesenteric, and mandibular lymph nodes occurred, but without an effect on
      antibody responses to KLH or tetanus. At 16-weeks recovery, microscopic compound
      related changes observed after 6 months of treatment were completely reversed
      (0.1 mg/kg group) and partially reversed (1.0 and 30.0 mg/kg groups), while
      peripheral blood B cells remained 66-72% reduced from baseline. Despite reduced
      germinal centres in lymphoid organs, and reductions in circulating B cells, T
      cell-dependent humoral immunity was maintained following tabalumab administration
      in three safety studies in cynomolgus monkeys. 

PMID- 25585961
TI  - Chemotherapy-free treatment in patients with follicular lymphoma.
AB  - The outcome of patients with follicular lymphoma (FL) has improved over the last
      two decades through the introduction of anti-CD20 monoclonal antibodies, usually
      used in combination with chemotherapy. However, patients with FL still experience
      multiple relapses, requiring several lines of treatment. Early toxicity of
      chemotherapy is a significant concern and as the life expectancy of patients with
      FL is increasing, late toxicities become an increasingly important concern.
      Progress made in understanding the biology of FL, especially dysregulation of
      intracellular pathways and immunological antitumor responses, recently allowed
      for the development of innovative chemo-free therapeutic approaches. In this
      report, different options such as new anti-CD20 antibodies, antibodies targeting
      other cell surface antigens, bi-specific antibodies, immunomodulation, idiotype
      vaccine and other targeted therapies are presented. The article also highlights
      how, although promising in early phase studies, the cost-effectiveness of new
      agents will have to be justified in Phase III trials. Furthermore, chemo-free
      regimen might not mean toxicity-free treatment and monitoring of early and late
      toxicities is required. 

PMID- 25585960
TI  - Psychosocial functioning in first-episode psychosis and associations with
      neurocognition, social cognition, psychotic and affective symptoms.
AB  - AIM: Most studies on the determinants of psychosocial functioning in first
      episode psychosis used few predictors. This study examines the effects of
      multiple cognitive domains and multiple symptoms on psychosocial functioning.
      METHODS: A total of 162 patients with a first-episode psychosis were assessed
      within 3 months after referral to an early psychosis treatment department. Four
      psychopathological subdomains (positive and negative symptoms, depression and
      anxiety) and five subdomains of psychosocial functioning (work/study,
      relationships, self-care, disturbing behaviour and general psychosocial
      functioning) were measured. Neurocognitive and social cognitive factors were
      identified through principal component analyses (PCA) of a 15-measure cognitive
      battery. Stepwise backward regression models were computed to identify the
      determinants of psychosocial functioning. RESULTS: The three neurocognitive and
      four social cognitive factors identified through PCA were largely independent of
      psychopathology. The strongest associations were between cognitive factors and
      anxiety. Higher levels of negative symptoms, poor general neurocognition and poor
      general social cognition showed strongest associations with impaired psychosocial
      functioning, followed by low verbal processing speed and low emotion processing
      speed. Together, these factors accounted for 39.4% of the variance in
      psychosocial functioning. CONCLUSIONS: The results suggest that negative
      symptoms, impaired neurocognition and poor social cognition are related to
      psychosocial problems in patients with first-episode psychosis. None of the
      affective or positive symptoms had a marked impact on psychosocial functioning.

PMID- 25585962
TI  - Pharmacological treatment of sleep disorders and its relationship with
      neuroplasticity.
AB  - Sleep and wakefulness are regulated by complex brain circuits located in the
      brain stem, thalamus, subthalamus, hypothalamus, basal forebrain, and cerebral
      cortex. Wakefulness and NREM and REM sleep are modulated by the interactions
      between neurotransmitters that promote arousal and neurotransmitters that promote
      sleep. Various lines of evidence suggest that sleep disorders may negatively
      affect neuronal plasticity and cognitive function. Pharmacological treatments may
      alleviate these effects but may also have adverse side effects by themselves.
      This chapter discusses the relationship between sleep disorders, pharmacological
      treatments, and brain plasticity, including the treatment of insomnia,
      hypersomnias such as narcolepsy, restless legs syndrome (RLS), obstructive sleep
      apnea (OSA), and parasomnias. 

PMID- 25585963
TI  - Oscillation of cAMP and Ca(2+) in cardiac myocytes: a systems biology approach.
AB  - Cyclic adenosine monophosphate (cAMP) and Ca(2+) levels may oscillate in harmony
      within excitable cells; a mathematical oscillation loop model, the Cooper model,
      of these oscillations was developed two decades ago. However, in that model all
      adenylyl cyclase (AC) isoforms were assumed to be inhibited by Ca(2+), and it is
      now known that the heart expresses multiple AC isoforms, among which the type 5/6
      isoforms are Ca(2+)-inhibitable whereas the other five (AC2, 3, 4, 7, and 9) are
      not. We used a computational systems biology approach with CellDesigner
      simulation software to develop a comprehensive graphical map and oscillation loop
      model for cAMP and Ca(2+). This model indicated that Ca(2+)-mediated inhibition
      of AC is essential to create oscillations of Ca(2+) and cAMP, and the
      oscillations were not altered by incorporation of phosphodiesterase-mediated cAMP
      hydrolysis or PKA-mediated inhibition of AC into the model. More importantly,
      they were created but faded out immediately in the co-presence of Ca(2+)
      noninhibitable AC isoforms. Because the subcellular locations of AC isoforms are
      different, spontaneous cAMP and Ca(2+) oscillations may occur within microdomains
      containing only Ca(2+)-inhibitable isoforms in cardiac myocytes, which might be
      necessary for fine tuning of excitation-contraction coupling.

PMID- 25585965
TI  - Immunohistochemical analysis of HMGA2 expression fails to provide evidence of a
      neoplastic basis for 'primary' synovial lipomatosis.

PMID- 25585964
TI  - Muscle and joint responses during and after static stretching performed at
      different intensities.
AB  - PURPOSE: We investigated the effects of plantarflexor static stretching of
      different intensities on the medial gastrocnemius (GAS) shear elastic modulus,
      GAS fascicle length and ankle passive torque-angle responses during and after
      stretching. METHODS: Participants performed three stretching sessions of
      different intensities: 40 % (R40) of maximal dorsiflexion range of motion (ROM),
      60 % (R60) of ROM, and 80 % (R80) of ROM. Each stretching lasted 10 min. The GAS
      architecture, GAS shear elastic modulus, ankle passive torque-angle, and muscle
      activity were assessed before, during, and after the stretching. RESULTS: The
      absolute and relative (i.e., normalized to the static stretching start value) GAS
      shear elastic modulus relaxation varied across stretching intensities. The
      absolute passive torque relaxation varied across intensities (p < 0.05) but not
      when normalized to the stretching start value. No significant changes were
      observed in GAS fascicle length during the stretching (p = 0.93). After
      stretching, passive torque at a given angle was significantly decreased for R60 [
      0.99 +/- 0.59 Nm (-6.5 +/- 3.8 %), p < 0.001] and R80 [-1.05 +/- 1.12 Nm (-6.8 +/
      6.3 %), p = 0.004], and GAS shear elastic modulus decreased only for the R80 [
      9.3 +/- 7.2 kPa (-14.1 %), p = 0.003]. No significant correlations were found
      between the magnitude of relaxation during stretching and post-stretching effect
      in the GAS shear elastic modulus or ankle passive torque variables. No
      significant relation was found between the shear elastic modulus and the ankle
      passive torque responses during and after stretching. CONCLUSION: The effects of
      stretching on joint passive torque do not reflect changes in the medial
      gastrocnemius shear elastic modulus, and these responses to stretching depend on
      its intensity.

PMID- 25585966
TI  - Novel investigational drugs targeting IL-6 signaling for the treatment of
      depression.
AB  - INTRODUCTION: Elevated levels of IL-6 have been implicated in the pathophysiology
      and treatment of major depressive disorder (MDD). Convergent evidence suggests
      that IL-6 primarily mediates proinflammatory functions via the soluble IL-6
      receptor/trans-signaling, and anti-inflammatory functions via a transmembrane
      receptor (IL-6R). A targeted approach to selectively inhibit IL-6 trans-signaling
      may offer putative antidepressant effects. AREAS COVERED: This review addresses
      three primary domains. The first focuses on the biological role of IL-6 within
      inflammation and its signal transduction pathways. The second addresses the
      potential contributions of IL-6 to the pathophysiology of MDD, and the mechanisms
      that may mediate these effects. Finally, the article outlines the therapeutic
      benefits of incorporating anti-inflammatory properties into the pharmacological
      treatment of MDD, and proposes inhibition of IL-6 signaling as a viable treatment
      strategy. EXPERT OPINION: To improve drug development for the treatment of MDD,
      there is a critical need to identify promising targets. Target identification
      will require guidance from a strategic framework such as The Research Domain
      Criteria, and convincing evidence relating known targets to brain function under
      both physiological and pathological conditions. Although current evidence
      provides rationale for administering anti-IL-6 treatments in MDD, further studies
      confirming safety, target affinity and therapeutic benefits are warranted.

PMID- 25585968
TI  - Self referral for cancer tests is to be piloted in England.

PMID- 25585967
TI  - Structural and biophysical characterization of human cytochromes P450 2B6 and 2A6
      bound to volatile hydrocarbons: analysis and comparison.
AB  - X-ray crystal structures of complexes of cytochromes CYP2B6 and CYP2A6 with the
      monoterpene sabinene revealed two distinct binding modes in the active sites. In
      CYP2B6, sabinene positioned itself with the putative oxidation site located
      closer to the heme iron. In contrast, sabinene was found in an alternate
      conformation in the more compact CYP2A6, where the larger hydrophobic side chains
      resulted in a significantly reduced active-site cavity. Furthermore, results from
      isothermal titration calorimetry indicated a much more substantial contribution
      of favorable enthalpy to sabinene binding to CYP2B6 as opposed to CYP2A6,
      consistent with the previous observations with (+)-alpha-pinene. Structural
      analysis of CYP2B6 complexes with sabinene and the structurally similar (3)
      carene and comparison with previously solved structures revealed how the movement
      of the F206 side chain influences the volume of the binding pocket. In addition,
      retrospective analysis of prior structures revealed that ligands containing -Cl
      and -NH functional groups adopted a distinct orientation in the CYP2B active site
      compared with other ligands. This binding mode may reflect the formation of Cl-pi
      or NH-pi bonds with aromatic rings in the active site, which serve as important
      contributors to protein-ligand binding affinity and specificity. Overall, the
      findings from multiple techniques illustrate how drugs metabolizing CYP2B6 and
      CYP2A6 handle a common hydrocarbon found in the environment. The study also
      provides insight into the role of specific functional groups of the ligand that
      may influence the binding to CYP2B6. 

PMID- 25585969
TI  - Novel Use of Pharmacogenetic Testing in the Identification of CYP2C9
      Polymorphisms Related to NSAID-Induced Gastropathy.
AB  - OBJECTIVE: To illustrate the potential value of pharmacogenetic testing to
      identify patients at risk for nonsteroidal anti-inflammatory drug-induced
      gastropathy. DESIGN: Case report. SETTING: We report a case encountered in an
      outpatient setting for pain management. PATIENT: We present a case of a patient
      treated with celecoxib who developed severe nonsteroidal anti-inflammatory drug
      induced gastropathy. INTERVENTION: Suspecting a relation between this adverse
      event and altered drug metabolism, pharmacogenetic testing was performed to
      assess the role of the cytochrome P450 (CP450) enzyme profile. RESULTS:
      Pharmacogenetic testing revealed a relation between this adverse event and an
      allelic variant of cytochrome P450, CYP2C9, subsequently leading to
      discontinuation of the drug along with counseling to caution the patient to avoid
      the use of celecoxib and other drugs metabolized by the same enzyme. CONCLUSION:
      Although pharmacogenetic testing is not routinely used in clinical decision
      making, pain physicians must be aware of the potential benefits of this testing
      for managing patients with pain, and to improve drug efficacy and safety profile.

PMID- 25585971
TI  - Early outcomes of macular hole surgery on visual acuity, retinal anatomy and
      vision-related quality of life.

PMID- 25585970
TI  - Association of increased carotid intima-media thickness and lower plasma levels
      of vitamin C and vitamin E in old age subjects: implications for Alzheimer's
      disease.
AB  - In light of the recent advances regarding the role of vascularity in Alzheimer's
      disease (AD) pathophysiology, the relationship between plasma levels and
      activities of the major antioxidant molecules and the carotid intima-media
      thickness (C-IMT) of older persons with no or very mild cognitive impairment was
      evaluated. The underlying hypothesis is that the IMT may be an indirect index of
      vascular damage in persons with low levels of plasma antioxidants. Plasma levels
      of vitamins A, C, E, of uric acid as well as activities of the plasma antioxidant
      enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) were
      measured. Plasma levels of vitamins C and E significantly decreased among
      participants from the first to the fourth IMT quartile, with a linear slope only
      for vitamin C. Compared to participants in the lowest vitamin C quartile, the
      probability to have IMT >1.2 mm significantly decreased among persons from the
      second to the fourth quartile independent of confounders. In conclusion, only
      vitamin C plasma levels appear to be selectively associated with the risk of
      increasing C-IMT. An adequate vitamin C status might be particularly important
      for protection against AD and other clinical manifestations of vascular and
      cognitive ageing.

PMID- 25585973
TI  - [Vertigo and syncope: a clinically oriented introduction to the problem].
AB  - Vertigo and syncope are frequently occurring clinical presentations in the
      physician's practice as well as in the emergency room. Therefore, many physicians
      and institutions have formulated diagnostic protocols that they follow when a
      patient with vertigo or syncope presents. This kind of blanket routine may lead
      to over-diagnosis in many cases, as well as to under-diagnosis in some. The
      purpose of the following article is to show that a well-focused history based on
      clear cut concepts of disease and a sound pathophysiological understanding will
      guide the physician precisely through the diagnostic process in both clinical
      presentations and will help to avoid manifold diagnostic procedures. Finally, a
      description of the most frequent pitfalls of the diagnostic work-up is given,
      along with measures to avoid these. 

PMID- 25585972
TI  - Distinct regulation in inflorescence carbohydrate metabolism according to
      grapevine cultivars during floral development.
AB  - Carbohydrate metabolism is important in plant sexual reproduction because sugar
      contents are determining factors for both flower initiation and floral organ
      development. In woody plants, flowering represents the most energy-consuming step
      crucial to reproductive success. Nevertheless, in these species, the
      photosynthesis performed by flowers supplies the carbon required for
      reproduction. In grapevine (Vitis vinifera), the inflorescence has a specific
      status because this organ imports carbohydrates at the same time as it exports
      photoassimilates. In this study, fluctuations in carbohydrate metabolism were
      monitored by analyzing gas exchanges, photosynthetic electron transport capacity,
      carbohydrate contents and some activities of carbohydrate metabolism enzymes, in
      the inflorescences of Pinot noir and Gewurztraminer, two cultivars with a
      different sensitivity to coulure phenomenon. Our results showed that
      photosynthetic activity and carbohydrate metabolism are clearly different and
      differently regulated during the floral development in the two cultivars. Indeed,
      the regulation of the linear electron flow and the cyclic electron flow is not
      similar. Moreover, the regulation of PSII activity, with a higher Y(NPQ)/Y(NO)
      ratio in Gewurztraminer, can be correlated with the higher protection of the
      photosynthetic chain and consequently with the higher yield under optimal
      conditions of this cultivar. At least, our results showed a higher photosynthetic
      activity and a better protection of PSI in Pinot noir during the floral
      development. 

PMID- 25585974
TI  - Unilateral subretinal fibrosis and uveitis syndrome.
AB  - Subretinal fibrosis and uveitis syndrome is a rare, potentially devastating,
      posterior uveitis of unknown aetiology, characterised bilaterally by initial
      multifocal choroiditis with later progressive subretinal fibrosis. We report a
      rare case of unilateral subretinal fibrosis and uveitis syndrome. To date, there
      are only two case reports of unilateral disease. Our patient presented with
      unilateral blur and was found to have reduced visual acuity. A Bartonella profile
      was positive and a diagnosis of Bartonella posterior uveitis was made. Several
      positive ocular findings in the anterior chamber and on fundoscopy consistent
      with the syndrome were found. When steroid therapy alone could no longer control
      active inflammation, the immunosuppressive agent mycophenolate was added. Over
      time subretinal fibrosis became established sparing the macula and associated
      complications occurred, but with mycophenolate, at four years, our patient's
      visual acuity had improved and remains stable. Moreover, four years after her
      initial presentation, her condition remains strictly unilateral. 

PMID- 25585975
TI  - An update on newer pediatric supraglottic airways with recommendations for
      clinical use.
AB  - Supraglottic airways are an established part of routine and emergency pediatric
      airway management, including use in difficult airways and neonatal resuscitation.
      With the introduction of newer supraglottic airways in children, efficacy can
      only be determined by comparing these devices with those that are already well
      established (laryngeal mask airway Classic and laryngeal mask airway ProSeal).
      This narrative review aims to present the current literature on these newer
      supraglottic airways and give recommendations for their use in various clinical
      scenarios based on the existing evidence. 

PMID- 25585976
TI  - Bioelectromagnetic effects measurements - SAR and induced current.
AB  - The paper discusses several theoretical and practical aspects of the application
      of currents flowing through the body of a radiotelephone operator and Specific
      Absorption Rate (SAR). SAR is known as the physical quantity which is a perfect
      solution for biological experiments. Unfortunately, SAR cannot be measured
      directly. Contrary to SAR, which is limited to the penetration depth, a current
      induced in a point of a body is measurable in any other point of the body. The
      main objective of this paper is to show that the current induced in a human body
      when using a radiotelephone or mobile phone is significant and should be analyzed
      as widely as SAR is. Computer simulations of a human's hand with a radiotelephone
      were made. Experiments were also conducted. The results of the experiments show
      that induced current is also as important as SAR and it cannot be omitted in
      bioelectromagnetic experiments. In biomedical studies both parameters: induced
      current and SAR play a major role.

PMID- 25585977
TI  - Pore cross-section area on predicting elastic properties of trabecular bovine
      bone for human implants.
AB  - A clear understanding of the dependence of mechanical properties of bone remains
      a task not fully achieved. In order to estimate the mechanical properties in
      bones for implants, pore cross-section area, calcium content, and apparent
      density were measured in trabecular bone samples for human implants. Samples of
      fresh and defatted bone tissue, extracted from one year old bovines, were cut in
      longitudinal and transversal orientation of the trabeculae. Pore cross-section
      area was measured with an image analyzer. Compression tests were conducted into
      rectangular prisms. Elastic modulus presents a linear tendency as a function of
      pore cross-section area, calcium content and apparent density regardless of the
      trabecular orientation. The best variable to estimate elastic modulus of
      trabecular bone for implants was pore cross-section area, and affirmations to
      consider Nukbone process appropriated for marrow extraction in trabecular bone
      for implantation purposes are proposed, according to bone mechanical properties.
      Considering stress-strain curves, defatted bone is stiffer than fresh bone.
      Number of pores against pore cross-section area present an exponential decay,
      consistent for all the samples. These graphs also are useful to predict elastic
      properties of trabecular samples of young bovines for implants. 

PMID- 25585978
TI  - Biologic properties of nano-hydroxyapatite: An in vivo study of calvarial
      defects, ectopic bone formation and bone implantation.
AB  - This study investigated the biologic properties of nano-hydroxyapatite (nHAp)
      using the rat calvarial defect, ectopic bone formation, and rabbit tibia implant
      installation models. Animals were divided into two groups: those implanted with
      nHAp, and negative controls (Collagen). Eight weeks after creating an 8 mm
      calvarial defect, bone regeneration was evaluated radiographically and
      histologically. To investigate ectopic bone formation, materials were injected
      into the right thigh muscle and were evaluated after 8 weeks. nHAp coated implant
      and conventional titanium implant were placed bilaterally in rabbit tibias. After
      4 weeks, bone-implant contact (BIC), new bone area inside the thread, and removal
      torque were measured. In the calvarial defect model, radiographic and histologic
      analysis showed more bone formation in the nHAp Group; particularly,
      histologically assessed bone area (p=0.034) and microcomputed tomography assessed
      bone mineral density (p=0.034). In the ectopic bone formation model,
      calcification and expression of osteogenic biomarkers were seen in the nHAp
      injected samples but in none of the controls. nHAp coated implant resulted in
      increased BIC, new bone area, and increased removal torque, with statistical
      significance for BIC (p=0.034). This study suggests that nHAp has potential as a
      coating material for dental implant surfaces and as a bone graft material. 

PMID- 25585979
TI  - Biosynthesis and in vitro evaluation of macroporous mineralized bacterial
      nanocellulose scaffolds for bone tissue engineering.
AB  - Macroporous bacterial nanocellulose (BNC) scaffolds with calcium phosphate coated
      surfaces is a candidate for future bone tissue engineering applications. The
      mineralization of the macroporous BNC scaffolds was achieved by a biomimetic
      process, resulting in an environment resembling native bone tissues' mineralized
      extra cellular matrix both topographically and chemically. The deposited crystals
      were analyzed with electron spectroscopy for chemical analysis (ESCA), energy
      dispersive X-ray spectroscopy (EDX) and X-ray crystallography (XRD). MSCs were
      cultured in osteogeneic medium for 21 days on the scaffolds. The results of this
      study show that macroporous BNC can be mineralized with hydroxyapatite and that
      MSCs retain their ability to proliferate and differentiate towards an
      osteoblastic phenotype within the mineralized BNC, showing the promise of this
      material in bone tissue engineering applications. 

PMID- 25585980
TI  - Electrochemical behaviour of a cobalt-chromium-molybdenum dental alloy in
      artificial salivas: Influence of phosphate ions and mucin components.
AB  - The stability of the Co-Cr-Mo dental alloy immersed in artificial salivas (pH
      6.7) was investigated over 24 h. Three artificial salivas have been studied:
      saline saliva (saliva I); saline saliva buffered with phosphate ions (saliva II)
      and saliva II plus mucin molecules (saliva III). For all the systems, open
      circuit potential shift positively over 24 hours of immersion. Data extracted
      from the steady-state polarization curves demonstrated that the Co-Cr-Mo alloy
      has higher corrosion potential in saliva III, lower corrosion potential in saliva
      I and lower initial corrosion resistance in saliva III. After 24 hours of
      immersion in the artificial salivas, the Co-Cr-Mo alloy presents high corrosion
      stability, due to the protective action created by the presence of corrosion
      products. From the analysis of the breakdown potential it was concluded that, the
      presence of the phosphate ions and mucin promote the oxidation process, inducing
      the formation of etch pits. Regarding the effect of the mucin concentration in
      the corrosion behaviour of the Co-Cr-Mo dental alloy, it was observed a negative
      shift in the corrosion potential, pointing to a cathodic inhibitor role for the
      mucin molecules. Nevertheless, no correlation between the mucin concentration and
      corrosion rate was possible to establish. 

PMID- 25585981
TI  - Effect of laser polishing on the surface roughness and corrosion resistance of
      Nitinol stents.
AB  - In this paper, we investigated the effect of laser polishing at different
      treatment times on the surface roughness and corrosion resistance of a biliary
      nickel-titanium (NiTi or Nitinol) stent. A specific area of the stent wire
      surface was checked for changes in roughness by scanning electron microscopy
      (SEM) and a noncontact profilometer. The corrosion resistance was assessed by
      potentiodynamic polarization test and electrochemical impedance spectroscopy. The
      surface characterization revealed that laser polishing reduced the surface
      roughness of stent by 34-64% compared to that of the as-received stent surface
      condition depending on the treatment time (i.e., 700-1600 MUm). Measurements
      using potentiodynamic polarization in simulated body fluid solution showed better
      anti-corrosion performance of laser-polished stent compared to magnetically
      polished stent and has comparable corrosion resistance with the as-received stent
      condition. In this paper, we have shown a preliminary study on the potential of
      laser polishing for the improvement of surface roughness of stent without
      affecting much its corrosion resistance. 

PMID- 25585982
TI  - Application of hydrophobic coatings in biodegradable devices.
AB  - BACKGROUND: Degradation periods of biodegradable medical devices strongly affect
      their clinical performance and therefore special attention has been drawn to
      modulate their degradation rate. OBJECTIVE: This paper presents an experimental
      study on the effect of hydrophobic coating on the degradation behavior of PLLA
      samples. METHODS: PLLA films were coated with a thin layer of PCL, and a
      combination of scanning electron microscopy (SEM), Ubbelohde Viscometer
      Capillary, and chromatograph of gel permeation (GPC) was used to evaluate the
      morphology and molecular weight changes of samples during degradation. In
      addition, the mass loss of samples was also measured during the experiment.
      RESULTS: PLLA samples with PCL coatings showed a slower degradation rate than
      those without PCL coatings, which indicated that PCL coatings could protect
      inside PLLA samples and slow down the degradation rate of PLLA samples.
      CONCLUSIONS: The results of the study suggest that hydrophobic coating on polymer
      materials is a useful approach to control the degradation of polymer medical
      device.

PMID- 25585983
TI  - Immobilization of phosphate monomers on collagen induces biomimetic
      mineralization.
AB  - BACKGROUND: Immobilization of phosphoproteins on type-I collagen via covalent
      binding may induce extra- and intrafibrillar mineralization. OBJECTIVE: This
      study tested the hypothesis that methacrylate phosphate esters immobilized on
      reconstituted type-I collagen can mimic the nucleating role of phosphoproteins.
      METHODS: Three functional monomers (MDP, GPDM and Phenyl-P) that differed in
      chemical structure and steric hindrances around the phosphate moiety were
      evaluated. Reconstituted type-I collagen was either left untouched (control) or
      treated by 5% monomer/ethanol for 20 s. All samples were incubated in simulated
      dentinal fluid as mineralizing medium at 37 degrees C for 7 or 14 days. The extra
      and intrafibrillar mineralization were examined by SEM and TEM/SAED
      crystallography, respectively. RESULTS: FT-IR spectroscopy showed that the
      phosphate groups were incorporated on reconstituted collagen, irrespective of
      their chemical structure. MDP immobilization induced dense growth of
      extrafibrillar mineral over time, while with GPDM- and Phenyl-P-immobilized
      collagen, mineralization was moderate and sparse, respectively. TEM/SAED evidence
      disclosed that intrafibrillar minerals exclusively occurred in MDP-immobilized
      collagen. CONCLUSIONS: Immobilization of MDP, which had the lowest steric
      hindrance, could induce significant biomimetic extra- and intrafibrillar
      mineralization; resembling the lowest level of hierarchy organization of dentin.

PMID- 25585984
TI  - Hemostatic action of EGF-endospray on mucosectomy-induced ulcer bleeding animal
      models.
AB  - Gastric bleeding is one of the irritant problems in ulcer patients. In this
      study, we evaluated hemostatic action of ulcer-coating powder (EGF-endospray) on
      gastric ulcer animal models. EGF-endospray, containing epidermal growth factor,
      is designed to be applied through an endoscope. Hemostatic action of the EGF
      endospray was evaluated on gastric hemorrhage models of rabbits and micro-pigs.
      The EGF-endospray was directly applied onto a mucosal resection (MR)-induced
      gastric bleeding focus in a rabbit model. In a porcine model, the EGF-endospray
      was applied once via an endoscopy to a bleeding lesion created by endoscopic
      submucosal dissection. The bleeding focus was then observed via an endoscope. In
      the rabbit model, EGF-endospray treatment significantly shortened mean bleeding
      time in comparison with other treatments (104.3 vs 548.0 vs 393.2 s for the EGF
      endospray, the non-treated control and the epinephrine injection, respectively).
      In the micro-pig model, EGF-endospray showed immediate hemostatic action and
      prolonged covering of the bleeding focus for over 72 h. Histology proved mucosal
      thickness was more efficiently recovered in all EGF-endospray treated animals.
      The results of the present study suggest that the EGF-endospray is a promising
      hemostatic agent for GI bleeding. 

PMID- 25585985
TI  - Comparative study of the biodegradability of porous silicon films in simulated
      body fluid.
AB  - The biodegradability of oxidized microporous, mesoporous and macroporous silicon
      films in a simulated body fluid with ion concentrations similar to those found in
      human blood plasma were studied using gravimetry. Film dissolution rates were
      determined by periodically weighing the samples after removal from the fluid. The
      dissolution rates for microporous silicon were found to be higher than those for
      mesoporous silicon of comparable porosity. The dissolution rate of macroporous
      silicon was much lower than that for either microporous or mesoporous silicon.
      This is attributed to the fact that its specific surface area is much lower than
      that of microporous and mesoporous silicon. Using an equation adapted from [Surf.
      Sci. Lett. 306 (1994), L550-L554], the dissolution rate of porous silicon in
      simulated body fluid can be estimated if the film thickness and specific surface
      area are known. 

PMID- 25585986
TI  - 'Going into the unknown': experiences of male patients in secure settings during
      environmental transition.
AB  - Little is known about the experiences of male patients in secure mental health
      and intellectual disability units during environmental transition. We interviewed
      patients before (n = 9) and after (n = 8) a side-to-side security transition from
      medium-secure wards in an older building to new wards in a purpose-built
      building. We inquired about transitional experiences in general and about this
      transition specifically. We examined interview transcripts and field notes using
      thematic analysis, and collated routine outcome data to gauge whether transition
      had obvious positive or negative effects. Qualitative analysis indicated three
      major themes (information, transition, and behaviour) and five overlapping
      subthemes (positive information sharing and consultation, concerns and anxieties
      about lack of information, life change and opportunity, home and sense of
      belonging, and potential conflict). Outcome data indicated little obvious change
      between first and second interviews. Expressed concerns of patients about
      transition were largely about tangible and practical issues, including changes to
      rules, including smoking and prohibited items. The results highlight the need for
      the development of supportive patient-inclusion strategies, consistent and
      transparent communication processes, and a published timeframe during the
      planning and implementation phases of all types of transitional moves, including
      the side-to-side transfer of residents between accommodation buildings. 

PMID- 25585987
TI  - Cytokine production suppression by culture supernatant of B16F10 cells and
      amelioration by Ganoderma lucidum polysaccharides in activated lymphocytes.
AB  - Some cytokines, such as interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and
      tumor necrosis factor-alpha (TNF-alpha), produced by lymphocytes might play an
      important role in anti-tumor immunity and their production is possibly suppressed
      by cancer. Amelioration of the suppression of cytokine production might
      contribute to cancer control. Ganoderma lucidum polysaccharides (Gl-PS), a
      versatile group of a component of G. lucidum and one with various bioactivities,
      might have this potential. In this study, analyses including reverse
      transcription and the polymerase chain reaction (RT-PCR), immunocytochemistry and
      Western blot were used to test the effects of Gl-PS on the production of IL-2,
      IFN-gamma and TNF-alpha in mononuclear lymphocytes by incubating Gl-PS with mouse
      splenic mononuclear lymphocytes in the presence of B16F10 cell culture
      supernatant following activation by phytohemagglutinin. The RT-PCR,
      immunocytochemistry and Western blot assays showed that the production of IL-2,
      IFN-gamma and TNF-alpha in mononuclear lymphocytes was suppressed by B16F10 cell
      culture supernatant at both the mRNA and protein levels, whereas the suppression
      was fully or partially ameliorated by Gl-PS. The amelioration by Gl-PS against
      the suppression of the production of IL-2, IFN-gamma and TNF-alpha in mononuclear
      lymphocytes by B16F10 cell culture supernatant might contribute to cancer
      control. 

PMID- 25585988
TI  - Acid-sensing ion channels (ASICs) 2 and 4.2 are expressed in the retina of the
      adult zebrafish.
AB  - Acid-sensing ion channels (ASICs) are H(+)-gated, voltage-insensitive cation
      channels involved in synaptic transmission, mechanosensation and nociception.
      Different ASICs have been detected in the retina of mammals but it is not known
      whether they are expressed in adult zebrafish, a commonly used animal model to
      study the retina in both normal and pathological conditions. We study the
      expression and distribution of ASIC2 and ASIC4 in the retina of adult zebrafish
      and its regulation by light using PCR, in situ hybridization, western blot and
      immunohistochemistry. We detected mRNA encoding zASIC2 and zASIC4.2 but not
      zASIC4.1. ASIC2, at the mRNA or protein level, was detected in the outer nuclear
      layer, the outer plexiform layer, the inner plexiform layer, the retinal ganglion
      cell layer and the optic nerve. ASIC4 was expressed in the photoreceptors layer
      and to a lesser extent in the retinal ganglion cell layer. Furthermore, the
      expression of both ASIC2 and ASIC4.2 was down-regulated by light and darkness.
      These results are the first demonstration that ASIC2 and ASIC4 are expressed in
      the adult zebrafish retina and suggest that zebrafish could be used as a model
      organism for studying retinal pathologies involving ASICs. 

PMID- 25585990
TI  - Jack Lewis, professor the Lord Lewis of Newnham (1928-2014).

PMID- 25585989
TI  - Knowledge, attitudes and beliefs towards management of men with locally advanced
      prostate cancer following radical prostatectomy: an Australian survey of
      urologists.
AB  - OBJECTIVE: To investigate Australian urologists' knowledge, attitudes and
      beliefs, and the association of these with treatment preferences relating to
      guideline-recommended adjuvant radiotherapy for men with adverse pathologic
      features following radical prostatectomy. SUBJECTS AND METHODS: A nationwide
      mailed and web-based survey of Australian urologist members of the Urological
      Society of Australia and New Zealand (USANZ). RESULTS: 157 surveys were included
      in the analysis (45% response rate). Just over half of respondents (54%) were
      aware of national clinical practice guidelines for the management of prostate
      cancer. Urologists' attitudes and beliefs towards the specific recommendation for
      post-operative adjuvant radiotherapy for men with locally advanced prostate
      cancer were mixed. Just over half agreed the recommendation is based on a valid
      interpretation of the underpinning evidence (54.1%, 95% CI [46%, 62.2%]) but less
      than one third agreed adjuvant radiotherapy will lead to improved patient
      outcomes (30.2%, 95% CI [22.8%, 37.6%]). Treatment preferences were varied,
      demonstrating clinical equipoise. A positive attitude towards the clinical
      practice recommendation was significantly associated with treatment preference
      for adjuvant radiotherapy (rho = 0.520, P < 0.0001). There was stronger
      preference for adjuvant radiotherapy in more recently trained urologists
      (registrars) while preference for watchful waiting was greater in more
      experienced urologists (consultants) (b = 0.156, P = 0.034; 95% CI [0.048,
      1.24]). Urologists' attitudes towards clinical practice guidelines in general
      were positive. CONCLUSION: There remains clinical equipoise among Australian
      urologists in relation to adjuvant radiotherapy for men with adverse pathologic
      features following radical prostatectomy.

PMID- 25585991
TI  - Predictors for mild parkinsonian signs: a prospective population-based study.
AB  - OBJECTIVE: Mild parkinsonian signs (MPS) are common in the elderly population and
      are associated with a wide range of adverse health outcomes, including incident
      Parkinson's disease (PD). We aimed to prospectively evaluate potential risk
      factors for incident MPS. METHODS: Participants of the population-based Bruneck
      Study representative for the general elderly community underwent a baseline
      assessment of substantia nigra (SN)-echogenicity with transcranial sonography,
      olfactory function with the Sniffin' Sticks identification test and vascular risk
      according to the Framingham risk score as well as a baseline and 5-year follow-up
      neurological examination. MPS were defined according to established criteria
      based on the entire motor section of the Unified PD Rating Scale. Participants
      with PD at baseline or follow-up and subjects with MPS at baseline were excluded.
      A logistic regression analysis adjusted for age and sex was used to detect risk
      factors for incident MPS in the remaining 393 participants. RESULTS: SN
      hyperechogenicity and hyposmia were related to the development of MPS with odds
      ratios of 2.0 (95%CI, 1.1-3.7) and 1.6 (95%CI, 1.0-2.7), respectively, while
      increased vascular risk was not. Having both, SN-hyperechogenicity and hyposmia,
      was associated with an odds ratio of 3.0 (95%CI, 1.2-7.7) for incident MPS. Among
      the various motor domains, increased SN-echogenicity predicted the development of
      bradykinesia and rigidity, whereas diminished olfactory function predicted the
      development of impaired axial motor function. CONCLUSIONS: In addition to their
      established roles as risk factors for PD, SN-hyperechogenicity and hyposmia are
      associated with an increased risk for MPS in the general elderly community.

PMID- 25585993
TI  - Global long-term study on motor and non-motor symptoms and safety of levodopa
      carbidopa intestinal gel in routine care of advanced Parkinson's disease
      patients; 12-month interim outcomes.
AB  - INTRODUCTION: Intermittent oral delivery of levodopa is a major contributing
      factor for motor complications in Parkinson's disease (PD). Continuous infusion
      of levodopa-carbidopa intestinal gel (LCIG) into the jejunum using a portable
      pump via percutaneous endoscopic gastrostomy (PEG) improves motor complications
      and quality of life (QoL). OBJECTIVES: To record long-term effectiveness of
      advanced PD patients undergoing LCIG infusion in routine care, by Unified
      Parkinson's Disease Rating Scale (UPDRS), Non-Motor Symptoms Scale (NMSS), PDQ-8
      and EQ-5D questionnaires. METHODS: Overall, 375 patients from 75 movement
      disorder centers in 18 countries were enrolled in this prospective non
      interventional study. The 12-month interim outcomes of the first 172 included
      patients are presented here. RESULTS: There were reductions of mean daily "Off"
      time from baseline (BL) (7.1 +/- 3.5 h) and "On" time with dyskinesias (5.2 +/-
      4.5 h) at month 12 (M12) of -4.7 +/- 3.4 and -1.7 +/- 5.0 h respectively (p <
      0.0001; p = 0.0228). UPDRS II and III "On" scores decreased from BL to M12 (p =
      0.0107 and p = 0.0128). Total NMSS and PDQ-8 scores improved at M12 (p = 0.0014
      and p = 0.0100). Mean LCIG dose administered through PEG at first visit (day
      after implantation) was 1304 +/- 618 mg/day and remained stable through M12.
      Continuous LCIG infusion tolerability and adverse drug reactions were consistent
      with the known safety profile of previous studies. CONCLUSIONS: This
      observational, routine-care study supports long-term safety and efficacy of LCIG
      infusion in advanced PD including motor, non-motor and QoL improvements.

PMID- 25585994
TI  - Evidence for polymerase gamma, POLG1 variation in reduced mitochondrial DNA copy
      number in Parkinson's disease.
AB  - BACKGROUND: It remains unclear whether the mtDNA content is related to the
      clinicopathological prognosis in Parkinson's disease (PD). METHODS/RESULTS: We
      analyzed the copy number of mtDNA using quantitative real-time PCR in 414 cases
      with PD and 231 healthy subjects from mainland of China. The level of mtDNA was
      significantly decreased in PD patients' peripheral blood as compared to that of
      healthy controls (p < 0.001). Furthermore, lower mtDNA copy number was more
      frequently detected (75%) in the older onset age group (>= 50 years old) than
      that in (49%) the younger group (<50 years old, p = 0.007), suggesting mtDNA
      content might be an important genetic event in PD progression. Using direct
      sequencing, we examined the mutations in the D-loop region of mtDNA in 318 PD
      patients. The results revealed that 17% of the PD patients carried mutations in
      the D-loop of mtDNA, and 55% of these mutations were heteroplasmic. In addition,
      PD patients harboring AA + AA genotype of c.2070-12T > A and c.2070-64G > A in
      POLG1 along with mutations in POLG1 had a significantly lower copy number of
      mtDNA than those of PD patients without POLG1 alterations. CONCLUSIONS: Our
      results provided evidence for a significantly lower of mtDNA copy number in PD
      patients and POLG1 variation for reducing mtDNA copy number in PD.

PMID- 25585992
TI  - TREM2 R47H variant and risk of essential tremor: a cross-sectional international
      multicenter study.
AB  - INTRODUCTION: Essential tremor (ET) is the most frequent movement disorder in
      adults. Its pathophysiology is not clearly understood, however there is growing
      evidence showing common etiologic factors with other neurodegenerative disorders
      such as Alzheimer's and Parkinson's diseases (AD, PD). Recently, a rare p.R47H
      substitution (rs75932628) in the TREM2 protein (triggering receptor expressed on
      myeloid cells 2; OMIM: *605086) has been proposed as a risk factor for AD, PD and
      amyotrophic lateral sclerosis (ALS). The objective of the study was to determine
      whether TREM2 p.R47H allele is also a risk factor for developing ET. METHODS:
      This was a cross-sectional multicenter international study. An initial case
      control cohort from Spain (n = 456 ET, n = 2715 controls) was genotyped. In a
      replication phase, a case-control series (n = 897 ET, n = 1449 controls) from
      different populations (Italy, Germany, North-America and Taiwan) was studied.
      Owed to the rarity of the variant, published results on p.R47H allele frequency
      from 14777 healthy controls from European, North American or Chinese descent were
      additionally considered. The main outcome measure was p.R47H (rs75932628) allelic
      frequency. RESULTS: There was a significant association between TREM2 p.R47H
      variant and ET in the Spanish cohort (odds ratio [OR], 5.97; 95% CI, 1.203
      29.626; p = 0.042), but it was not replicated in other populations. CONCLUSIONS:
      These results argue in favor of population-specific differences in the allelic
      distribution and suggest that p.R47H (rs75932628) variant may contribute to the
      susceptibility of ET in Spanish population. However, taking into account the very
      low frequency of p.R47H, further confirmatory analyses of larger ET series are
      needed.

PMID- 25585995
TI  - Hospitalization in Parkinson's disease: a survey of UK neurologists,
      geriatricians and Parkinson's disease nurse specialists.
AB  - INTRODUCTION: Care for people with Parkinson's admitted to hospital is often
      suboptimal and services for these patients vary. We conducted a national survey
      to document current service provision in the UK and to explore clinicians' views
      on standards of care and potential service improvements. METHOD: We used the
      mailing lists of British Geriatric Society Movement Disorder Section (BGS-MDS),
      British and Irish Neurologists' Movement Disorders Group (BRING-MD), and
      Parkinson's Disease Nurse Specialists Association (PDNSA) and invited
      participation by email with a link to an online survey (www.surveymonkey.com).
      The survey was posted in spring 2014 for six weeks. RESULTS: There were 93
      respondents from at least 65 different hospitals. The estimated response rate was
      19%. Respondents were: 35 consultant geriatricians; 21 consultant neurologists,
      29 Parkinson's Disease Nurse Specialists (PDNS), 8 others. 81% respondents report
      their hospital has a PDNS. 79% have a geriatrician with an interest in
      Parkinson's. 54% have a Parkinson's clinical guideline, 16% a cohort/specialist
      ward for Parkinson's and 11% an electronic system for flagging Parkinson's
      admissions. 21% rated overall standard of care as poor. 61% were not confident
      that medications were given on time. Having a PDNS see all Parkinson's in
      patients, flagging of Parkinson's admissions and having a Parkinson's outreach
      service were ranked most likely of 16 potential service developments to improve
      care. CONCLUSION: Care for Parkinson's in-patients is not highly rated by UK
      Parkinson's clinicians. Interventions to improve care need to be studied but wide
      variations in current service provision pose a challenge for future study design.

PMID- 25585996
TI  - ApoE type 4 allele affects cognitive function of aged population in Tianjin City,
      China.
AB  - Apolipoprotein E type 4 allele (ApoE?4) is known as a risk gene for the late
      onset Alzheimer's disease, and the relationship between ApoE?4 and cognitive
      function of the elderly people has drawn the attention of the scientists. In this
      study, we investigated the relationship between ApoE?4 and the cognitive function
      of the old people. A total of 156 old people were investigated, of whom 31 were
      ApoE?4 carriers. The ApoE?4 primarily influenced the global cognitive function,
      perceptual speed, and work memory. The results indicate that ApoE?4 has
      significant negative effect on the cognitive function of the elderly people who
      are 60 years and older. 

PMID- 25585997
TI  - Erastin sensitizes glioblastoma cells to temozolomide by restraining xCT and
      cystathionine-gamma-lyase function.
AB  - Glioblastoma multiforme (GBM) is one of the most common encephalic malignant
      tumors. Due to a high recurrence rate and a lack of effective treatments, the
      average survival rate remains low. Temozolomide (TMZ), a class of alkylating
      agent, is widely used as a first-line therapeutic drug during the adjuvant
      treatment for GBM patients. However, most patients exhibit a palpable resistance
      to TMZ treatment. Additionally, the underlying mechanism remains to be clarified.
      In this study, glutathione (GSH) and reactive oxygen species (ROS) levels were
      found to be closely associated with the sensitivity of GBM cells to TMZ. We also
      found that TMZ markedly induced xCT, the subunit of glutamate/cystine transporter
      system xc- expression, which together with the GSH synthesis was increased while
      the TMZ-inducible ROS level was decreased in GBM cells. In addition, the
      cystathionine gamma-lyase (CTH) acivity, a key enzyme in the transsulfuration
      pathway was enhanced by TMZ, which insured a cysteine supply and GSH synthesis in
      a compensatory manner when xCT was blocked. Thus, the individual inhibition of
      xCT by siRNA and a pharmacological inhibitor (sulfasalazine) only partially
      inhibited GSH synthesis and moderately enhanced the GBM cell sensitivity to TMZ.
      However, the TMZ-induced cytotoxicity was markedly increased along with a marked
      decrease in GSH levels as result of co-treatment with erastin, which inhibited
      cysteine uptake from xCT transporter and suppressed CTH activity, leading to
      impaired transformation from methionine to cysteine. In conclusion, to GBM
      therapy with a drug combination of TMZ and erastin may be beneficial.

PMID- 25585998
TI  - Tocotrienol preserves ovarian function in cyclophosphamide therapy.
AB  - INTRODUCTION: Cyclophosphamide (CPA) chemotherapy leads to ovarian failure and
      infertility. Tocotrienol (T3) is an antioxidant and anti-inflammatory agent. The
      role of T3 in ovarian protection throughout chemotherapy remains unclear. AIM: To
      investigate the role of T3 in the preservation of female fertility in CPA
      treatment. METHOD: Sixty female mice were divided into five treatment groups,
      namely, normal saline, corn oil only, T3 only, CPA and CPA + T3. The treatment
      was given for 30 days, followed by administration of gonadotrophin to induce
      ovulation. After killing, both ovaries were collected and examined
      histologically. RESULTS: There was significant reduction in ovarian size in the
      CPA group compared with the normal group (CPA versus normal, mean area +/- SD;
      0.118 +/- 0.018 vs. 0.423 +/- 0.024 cm(2); p <= 0.005), whilst concurrent
      administration of T3 with CPA leads to conservation of ovarian size (CPA + T3 vs.
      CPA, mean area +/- SD; 0.285 +/- 0.032 vs. 0.118 +/- 0.018 cm(2); p <= 0.005).
      Ovaries in CPA group showed abnormal folliculogenesis with accompanied reduced
      ovulation rate, follicular oedema, increased vascularity and inflammatory cell
      infiltration. These changes were reversed by concurrent T3 administration.
      CONCLUSION: Co-administration of T3 with CPA confers protection of ovarian
      morphology and function in vivo. These findings contribute to the further
      elucidation of CPA effect on ovary and suggest the potential of T3 use in
      preserving fertility in chemotherapy.

PMID- 25585999
TI  - The important role of ADAM8 in the progression of hepatocellular carcinoma
      induced by diethylnitrosamine in mice.
AB  - This study focuses on investigating the concrete role of a disintegrin and
      metalloproteinase 8 (ADAM8) in the progression of hepatocellular carcinoma (HCC).
      Mice received anti-ADAM8 monoclonal antibody (mAb) of 100 MUg/100 MUl, 200
      MUg/100 MUl or 300 MUg/100 MUl, respectively, in phosphate-buffered saline (PBS)
      or PBS intervention during the progression of HCC induced by diethylnitrosamine.
      The survival rate, body weight, and relative liver weight were determined in the
      mice. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and
      alpha-fetoprotein (AFP) level, hematoxylin-eosin staining, the expression level
      of vascular endothelial growth factor A (VEGF-A), proliferating cell nuclear
      antigen (PCNA), caspase 3 (Casp3), B cell leukemia 2 (Bcl2), B cell leukemia 2
      associated X protein (Bax), protein p53 (P53), and ADAM8 were detected in the
      mice at the end of the 24th week. Our results showed that anti-ADAM8 mAb
      intervention effectively improved the survival rate, reduced the body weight loss
      and increased the relative liver weight in mice in a dose-dependent manner (p <
      0.05 or p < 0.01). Anti-ADAM8 mAb intervention also significantly lowered serum
      AST, ALT, and AFP levels (p < 0.05 or p < 0.01), slowed the progression of HCC (p
      < 0.05 or p < 0.01), induced the expression of Casp3, Bax, and P53 (p < 0.05 or p
      < 0.01), and inhibited the expression of VEGF-A, PCNA, and Bcl2 in the liver of
      mice (p < 0.05 or p < 0.01) in a dose-dependent manner compared with the mice
      receiving PBS intervention. Our study suggested that ADAM8 might promote the
      progression of HCC by regulating the expression of these factors. Anti-ADAM8 mAb
      intervention might be suitable as a potential method for HCC therapy. 

PMID- 25586000
TI  - Silibinin mitigates zidovudine-induced hepatocellular degenerative changes,
      oxidative stress and hyperlipidaemia in rats.
AB  - Prolonged zidovudine (AZT) treatment in HIV-infected and AIDS patients is shown
      to induce liver toxicity leading to complications. Therapeutic regimen that could
      encounter this adverse effect is unavailable and management of toxicity is often
      symptomatic or is limited to withdrawal of therapy. In the present investigation,
      we evaluated the alleviating properties of silibinin (SBN), a flavanolignan
      obtained from Silybum marianum against subacute AZT-induced hepatotoxicity and
      oxidative stress in rats. AZT treatment (50 mg/kg body weight (b.w.) periorally
      (p.o.), daily for 45 days) caused highly significant increases in alanine
      transaminase, alkaline phosphatase, argininosuccinic acid lyase and bilirubin in
      serum. Oxidative stress is shown by a highly significant increase in lipid
      peroxidase and total carbonyl content and decrease in catalase and protein thiols
      in the liver tissue. Hyperlipidaemia is indicated by highly significant increase
      in total lipids and free fatty acid in serum. Evaluation of liver by haematoxylin
      and eosin staining shows parenchymal cell enlargement, inflammatory changes and
      increase in sinusoidal spaces. Simultaneous treatment of SBN (100 mg/kg b.w.
      p.o., daily for 45 days) significantly protected the liver against
      hepatotoxicity, oxidative stress and hyperlipidaemia induced by AZT, and this
      alleviating property is attributed to hepatoprotective, membrane-stabilizing,
      antioxidant and free radical scavenging properties of SBN. 

PMID- 25586001
TI  - Mechanistic approach for the toxic effects of perfluorooctanoic acid on isolated
      rat liver and brain mitochondria.
AB  - BACKGROUND: Perfluorooctanoic acid (PFOA) is one of the most widely used
      perfluoroalkanes as surfactants, lubricants and processing aids in the production
      of polymers, which has also been detected in the environment, wildlife and human
      body. Animal studies indicated that PFOA caused a wide array of toxic effects
      including liver and brain dysfunction, carcinogenicity and reproductive and
      developmental toxicity. Based on the established role of mitochondria-mediated
      pathways in the observed toxic effects of many drugs and chemicals, in this
      study, the potential toxic effects of PFOA on mitochondria isolated from rat
      liver and brain have been investigated. METHOD: Mitochondria were isolated by
      differential centrifugation method and incubated with different concentrations of
      PFOA (0.5-1.5 mM). The effects of PFOA were assessed on a series of mitochondrial
      parameters including reactive oxygen species (ROS) formation, activities of
      mitochondrial complexes I/II/III, reduced glutathione (GSH) content, adenosine
      triphosphate (ATP) level, membrane potential, lipid peroxidation (LPO),
      mitochondrial swelling and cytochrome c release. RESULTS: The data on liver
      mitochondria indicated that PFOA-induced ROS elevation in both mitochondrial
      complexes I and III, mitochondrial membrane potential collapse, swelling,
      cytochrome c release and decreased ATP level which induces apoptosis or necrosis.
      On brain mitochondria, PFOA showed fairly similar effects on the above-mentioned
      parameters. However, different results were obtained when the effect of PFOA was
      assessed on LPO and complex II activity. CONCLUSIONS: Due to the fact that PFOA
      had toxic effects on the mitochondria isolated, it could be suggested that
      mitochondrial toxicity could be a plausible mechanism for the toxic effects of
      this fluorochemical on liver and brain function.

PMID- 25586002
TI  - X-ray radiation promotes the metastatic potential of tongue squamous cell
      carcinoma cells via modulation of biomechanical and cytoskeletal properties.
AB  - This study investigated the metastatic potential of tongue squamous cell
      carcinoma (TSCC) cells after X-ray irradiation as well as radiation-induced
      changes in the biomechanical properties and cytoskeletal structure that are
      relevant to metastasis. Tca-8113 TSCC cells were X-ray-irradiated at increasing
      doses (0, 1, 2, or 4 Gy), and 24 h later, migration was evaluated with the wound
      healing and transwell migration assays, while invasion was assessed with the
      Matrigel invasion assay. Confocal and atomic force microscopy were used to
      examine changes in the structure of the actin cytoskeleton and Young's modulus
      (cell stiffness), respectively. X-ray radiation induced dose-dependent increases
      in invasive and migratory potentials of cells relative to unirradiated control
      cells (p < 0.05). The Young's modulus of irradiated cells was decreased by
      radiation exposure (p < 0.05), which was accompanied by alterations in the
      integrity and organization of the cytoskeletal network, as evidenced by a
      decrease in the signal intensity of actin fibers (p < 0.05). X-ray irradiation
      enhanced migration and invasiveness in Tca-8113 TSCC cells by altering their
      biomechanical properties and the organization of the actin cytoskeleton. A
      biomechanics-based analysis can provide an additional platform for assessing
      tumor response to radiation and optimization of cancer therapies. 

PMID- 25586003
TI  - Effects of augmented trunk stabilization with external compression support on
      shoulder and scapular muscle activity and maximum strength during isometric
      shoulder abduction.
AB  - The aim of the present study was to investigate the effects of augmented trunk
      stabilization with external compression support (ECS) on the electromyography
      (EMG) activity of shoulder and scapular muscles and shoulder abductor strength
      during isometric shoulder abduction. Twenty-six women volunteered for the study.
      Surface EMG was used to monitor the activity of the upper trapezius (UT), lower
      trapezius (LT), serratus anterior (SA), and middle deltoid (MD), and shoulder
      abductor strength was measured using a dynamometer during three experimental
      conditions: (1) no external support (condition-1), (2) pelvic support (condition
      2), and (3) pelvic and thoracic supports (condition-3) in an active therapeutic
      movement device. EMG activities were significantly lower for UT and higher for MD
      during condition 3 than during condition 1 (p < 0.05). The MD/UT ratio was
      significantly higher during condition 3 than during conditions 1 and 2, and
      higher during condition 2 than during condition 1 (p < 0.05). Shoulder abductor
      strength was significantly higher during condition 3 than during condition 1 (p <
      0.05). These findings suggest that augmented trunk stabilization with the ECS may
      be advantageous with regard to reducing the compensatory muscle effort of the UT
      during isometric shoulder abduction and increasing shoulder abductor strength.

PMID- 25586004
TI  - The crystal structure of the catalytic domain of the ser/thr kinase PknA from M.
      tuberculosis shows an Src-like autoinhibited conformation.
AB  - Signal transduction mediated by Ser/Thr phosphorylation in Mycobacterium
      tuberculosis has been intensively studied in the last years, as its genome
      harbors eleven genes coding for eukaryotic-like Ser/Thr kinases. Here we describe
      the crystal structure and the autophosphorylation sites of the catalytic domain
      of PknA, one of two protein kinases essential for pathogen's survival. The
      structure of the ligand-free kinase domain shows an auto-inhibited conformation
      similar to that observed in human Tyr kinases of the Src-family. These results
      reinforce the high conservation of structural hallmarks and regulation mechanisms
      between prokaryotic and eukaryotic protein kinases.

PMID- 25586006
TI  - Advanced life support (ALS) instructors experience of ALS education in Western
      Australia: a qualitative exploratory research study.
AB  - BACKGROUND: When cardiac arrest occurs, timely competent advanced life support
      (ALS) interventions by nursing staff can influence patient outcomes. Ongoing ALS
      education influences maintenance of competency and avoids skill decay.
      OBJECTIVES: To explore the methods of ALS education delivery for nurses in the
      workplace; describe the issues relating to maintaining ALS competency; explore
      ALS competency decay for nurses and develop recommendations for the provision of
      continuing ALS education. DESIGN: A qualitative exploratory design was used to
      study ALS education provision in the workplace. PARTICIPANTS: Data were collected
      from ALS nurse experts in Western Australia by face-to-face and phone interviews.
      METHODS: Semi-structured interviews were conducted and organised around a set of
      predetermined questions. RESULTS: Two major themes were identified; the first
      theme Demand and Supply describes the increasing demand for ALS education for
      nurses and the challenges with providing timely cost effective traditional face
      to-face ALS education. The second theme, Choosing The Best Education Options
      describes new ways to provide ALS education using emerging technologies.
      CONCLUSIONS: The study suggested that using e-learning methods would assist with
      educating the maximum amount of nurses in a timely manner and e-learning and
      teleconferencing offer opportunities to reach nurses in distant locations.
      Delivering ALS education more frequently than annually would increase skills
      maintenance and lessen skill decay. Further research is required to explore which
      blended e-learning model is best suited to ALS education.

PMID- 25586005
TI  - Technology-assisted congestive heart failure care.
AB  - The interface between eHealth technologies and disease management in chronic
      conditions such as chronic heart failure (CHF) has advanced beyond the research
      domain. The substantial morbidity, mortality, health resource utilization and
      costs imposed by chronic disease, accompanied by increasing prevalence, complex
      comorbidities and changing client and health staff demographics, have pushed the
      boundaries of eHealth to alleviate costs whilst maintaining services. Whilst the
      intentions are laudable and the technology is appealing, this nonetheless
      requires careful scrutiny. This review aims to describe this technology and
      explore the current evidence and measures to enhance its implementation. 

PMID- 25586007
TI  - Tick-borne pathogens and the vector potential of ticks in China.
AB  - Ticks, as obligate blood-sucking ectoparasites, attack a broad range of
      vertebrates and transmit a great diversity of pathogenic microorganisms. They are
      considered second only to mosquitoes as vectors of human disease, and the most
      important vector of pathogens of domestic and wild animals. Of the 117 described
      species in the Chinese tick fauna, 60 are known to transmit one or more diseases:
      36 species isolated within China and 24 species isolated outside China. Moreover,
      38 of these species carry multiple pathogens, indicating the potentially vast
      role of these vectors in transmitting pathogens. Spotted fever is the most common
      tick-borne disease, and is carried by at least 27 tick species, with Lyme disease
      and human granulocytic anaplasmosis ranked as the second and third most
      widespread tick-borne diseases, carried by 13 and 10 species, respectively. Such
      knowledge provides us with clues for the identification of tick-associated
      pathogens and suggests ideas for the control of tick-borne diseases in China.
      However, the numbers of tick-associated pathogens and tick-borne diseases in
      China are probably underestimated because of the complex distribution and great
      diversity of tick species in this country. 

PMID- 25586009
TI  - Effects of total flavones from Acanthopanax senticosus on L-type calcium
      channels, calcium transient and contractility in rat ventricular myocytes.
AB  - Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS), a traditional herbal
      medicine, has been widely used to treat ischemic heart disease. However, the
      underlying cellular mechanisms of its benefits to cardiac function remain
      unclear. The present study examined the effects of total flavones from AS (TFAS)
      on L-type Ca(2+) channel currents (ICa-L ) using the whole cell patch-clamp
      technique and on intracellular calcium ([Ca(2+) ]i ) handling and cell
      contractility in rat ventricular myocytes with the aid of a video-based edge
      detection system. Exposure to TFAS resulted in a concentration- and voltage
      dependent blockade of ICa-L , with the half-maximal inhibitory concentration
      (IC50 ) of 283.12 ug/mL and the maximal inhibitory effect of 36.49 +/- 1.95%.
      Moreover, TFAS not only increased the maximum current in the current-voltage
      relationship but also shifted the activation and inactivation curves of ICa-L
      toward the hyperpolarizing direction. Meanwhile, TFAS significantly reduced
      amplitudes of myocyte shortening and [Ca(2+) ]i with an increase in the time to
      10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr).
      Thus, the cardioprotective effects of TFAS may be attributed mainly to the
      attenuation of [Ca(2+) ]i through the direct inhibition of ICa-L in rat
      ventricular myocytes and consequent negative effect on myocardial contractility.

PMID- 25586008
TI  - Irritable bowel syndrome is significantly associated with somatisation in 840
      patients, which may drive bloating.
AB  - BACKGROUND: Psychological factors may influence persistence and perceived
      severity of symptoms in irritable bowel syndrome (IBS). Literature suggests that
      somatisation is associated with IBS. However, the relationship between IBS
      subtype, symptoms of IBS and somatisation is unclear. AIM: To examine this issue
      in a large cohort of secondary care patients. METHODS: Demographic and
      gastrointestinal (GI) symptom data were collected from 4224 adult patients via
      the Rome III questionnaire. Somatisation data were collected using the patient
      health questionnaire-12. Mean somatisation score and number of somatic symptoms
      were compared between IBS patients and controls with minimal GI symptoms, and
      between IBS subtypes using analysis of variance. Effect of level of somatisation
      on symptom frequency was compared according to IBS subtype using a chi(2) test.
      RESULTS: 840 patients met Rome III criteria for IBS, controls were 2137 patients
      with GI symptoms without IBS. Mean somatisation scores and number of somatic
      symptoms were higher in IBS vs. controls (P < 0.001), and in mixed stool pattern
      IBS (IBS-M), vs. IBS with constipation (IBS-C) or diarrhoea (IBS-D) (P < 0.001).
      High levels of somatisation were more prevalent in IBS-M (31.7%) vs. IBS-C
      (22.5%) or IBS-D (20.8%) (P = 0.003). For all IBS subtypes, high levels of
      somatisation were associated with a greater frequency of bloating or abdominal
      distension prior to logistic regression. CONCLUSIONS: IBS is strongly associated
      with higher levels of somatisation, particularly IBS-M. Bloating may be
      associated with higher levels of somatisation, perhaps explaining why it can be
      difficult to treat.

PMID- 25586010
TI  - Novel augmentation ileocystoplasty technique to manage non-compliant bladders in
      the presence of obstructed megaureters: the "fez procedure".
AB  - OBJECTIVES: To show the efficacy and safety of a novel modification of Studer's
      neobladder, herein defined as the "fez procedure." METHODS: The medical records
      of 21 children (mean age 9.4 +/- 1.3 years) who underwent the "fez procedure" at
      King Abdulaziz University Hospital, Jeddah, Saudi Arabia, to manage refractory
      poorly-compliant bladders and concomitantly obstructed megaureters were
      retrospectively reviewed. The patients had been previously managed by either
      preliminary cutaneous ureterostomy (17 patients) or temporary nephrostomy (four
      patients) to improve and stabilize the renal functions. The "fez procedure"
      entailed augmentation ileocystoplasty and the use of an afferent tubularized
      ileal loop for direct ureteroileal anastomosis. The augmented bladder together
      with the tubularized loop were fashioned as a "fez" with its tassel. The outcome
      measures were changes in cystometric capacity, bladder compliance, glomerular
      filtration rate, serum creatinine, technetium 99m-diethylene triamine pentaacetic
      acid diuretic renography (T1/2), ureteral diameter, vesicoureteral reflux,
      febrile urinary tract infections, continence and complications. RESULTS: The mean
      study follow-up period was 52.5 +/- 12.8 months. Means of changes of cystometric
      capacity (273.2 +/- 60.9 mL) and bladder compliance (15.6 +/- 4.2 mL/cm H2 O)
      were significant (P < 0.0001). Resolution of ureteral obstruction was documented
      with improved T1/2 and ureteral diameter (P < 0.0001, each) of all patients. The
      initially improved renal functions after ureterostomies or nephrostomies were
      maintained after "fez surgery," with non-significant changes in the improved
      glomerular filtration rate (P = 0.22) and serum creatinine (P = 0.18). None of
      the patients experienced ureteral restenosis, vesicoureteral reflux, febrile
      urinary tract infections, incontinence or significant complications. CONCLUSIONS:
      The "fez procedure" represents a versatile and successful surgical option for
      these selected patients, as it offers improved bladder capacity/compliance,
      resolution of ureteral obstruction and vesicoureteral reflux, preservation of the
      renal function, control of urinary tract infections and urinary continence, and
      acceptable morbidity.

PMID- 25586011
TI  - BiobraneTM and skin staples: beware of necrotic ulceration.
AB  - BiobraneTM is a product used for temporary wound coverage post major paediatric
      burn wound debridement. We report two cases of necrotic ulceration associated
      with the use of BiobraneTM with skin staples. We suggest securing BiobraneTM with
      alternatives such as adhesive tapes and glue to prevent the occurrence of this
      adverse outcome. 

PMID- 25586012
TI  - Synthesis of hybrid hollow sub-microspheres assisted by pre-added colloidal SiO2.
AB  - A novel method was developed to synthesize organic-inorganic hybrid hollow sub
      microspheres (HHSs) through the addition of colloidal SiO2. The hydrolysis rate
      of 3-(methacryloyloxy)propyltrimethoxysilane (MPS) was accelerated by SiO2
      particles; meanwhile, the condensation rate of the hydrolytic species was
      decelerated. Thus, the hydrolytic monomers and oligomers of MPS were preserved as
      emulsifiers. These emulsifiers can then emulsify the isopentyl acetate (PEA) to
      form a steady O/W emulsion. The HHSs were produced by subsequent free radical
      polymerization and removal of the oil core. The hydrolytic MPS acted as
      emulsifiers and polymerizable monomers at the emulsification and polymerization
      stage, respectively. Thus, extra emulsifiers, co-emulsifiers, and organic
      monomers were omitted, which simplified the synthesis process. The good
      dispersion of HHSs in water and oil, as well as the EDX results, indicated the
      organic-inorganic hybrid structure of HHSs.

PMID- 25586013
TI  - Low Schottky barrier black phosphorus field-effect devices with ferromagnetic
      tunnel contacts.
AB  - Black phosphorus (BP) has been recently unveiled as a promising 2D direct bandgap
      semiconducting material. Here, ambipolar field-effect transistor behavior of
      nanolayers of BP with ferromagnetic tunnel contacts is reported. Using TiO2/Co
      contacts, a reduced Schottky barrier <50 meV, which can be tuned further by the
      gate voltage, is obtained. Eminently, a good transistor performance is achieved
      in the devices discussed here, with drain current modulation of four to six
      orders of magnitude and a mobility of MUh ~ 155 cm(2) V(-1) s(-1) for hole
      conduction at room temperature. Magnetoresistance calculations using a spin
      diffusion model reveal that the source-drain contact resistances in the BP device
      can be tuned by gate voltage to an optimal range for injection and detection of
      spin-polarized holes. The results of the study demonstrate the prospect of BP
      nanolayers for efficient nanoelectronic and spintronic devices.

PMID- 25586014
TI  - Systematic review of prognostic factors for mortality in dogs with immune
      mediated hemolytic anemia.
AB  - BACKGROUND: Treatment of dogs with primary immune-mediated hemolytic anemia
      (IMHA) is difficult and frequently unrewarding. Prognostic factors have been
      evaluated in a number of previous studies, and identification of such factors
      would be beneficial to enable selection of appropriate therapeutic regimens and
      supportive care. OBJECTIVES: The aim of the current study was to undertake a
      critical appraisal of the risk of bias in evidence relating to prognostic
      indicators for mortality in dogs with IMHA. ANIMALS: Three hundred and eighty
      client-owned dogs with spontaneous primary idiopathic IMHA reported in 6 previous
      studies. METHODS: A systematic review was conducted to evaluate evidence relating
      to prognostic factors for mortality in dogs with primary IMHA. Search tools were
      employed to identify articles and a validated appraisal tool was used to assess
      the quality of individual studies by considering inclusion and exclusion
      criteria, measurement of prognostic, outcome and confounding variables, and
      statistical methods. RESULTS: Few studies evaluated prognostic indicators for
      IMHA in dogs, and all of these suffered from methodologic flaws in at least 1
      major area. Fifteen different variables were identified as prognostic indicators,
      with 2 variables identified by >1 study. CONCLUSIONS AND CLINICAL IMPORTANCE:
      There are few pieces of high-quality evidence available to enable estimation of
      prognosis for dogs presenting with primary IMHA.

PMID- 25586015
TI  - Final analysis of the efficacy and safety of omacetaxine mepesuccinate in
      patients with chronic- or accelerated-phase chronic myeloid leukemia: Results
      with 24 months of follow-up.
AB  - BACKGROUND: Omacetaxine, a protein synthesis inhibitor, is indicated in the
      United States for the treatment of patients with chronic-phase (CP) or
      accelerated-phase (AP) chronic myeloid leukemia (CML) with resistance and/or
      intolerance to 2 or more tyrosine kinase inhibitors. METHODS: The final analysis,
      with 24 months of follow-up, included additional efficacy and safety analyses to
      assess the benefit of long-term omacetaxine administration (1.25 mg/m(2) twice
      daily for 14 days every 28 days followed by 7 days every 28 days) in CP-CML and
      AP-CML patients receiving >3 cycles. RESULTS: Eighteen percent of CP-CML patients
      achieved a major cytogenetic response (MCyR) with a median duration of 12.5
      months (95% confidence interval [CI], 3.5 months to not reached [NR]); responses
      were maintained for >=12 months in 3 of 14 responders, and the median overall
      survival (OS) was 40.3 months (95% CI, 23.8 months to NR). Among patients with AP
      CML, 14% achieved or maintained a major hematologic response for a median of 4.7
      months (95% CI, 3.6 months to NR); MCyR was not achieved, and the median OS was
      14.3 months (95% CI, 6.7-18.7 months). In patients with CP-CML and patients with
      AP-CML who received >3 cycles of treatment (n = 50 and n = 14, respectively), the
      median OS was 49.3 months (95% CI, 23.8 months to NR) and 24.6 months (95% CI, 12
      37.2 months), respectively. Grade 3 or higher hematologic toxicities were the
      major side effects (79% and 73% for CP-CML and AP-CML, respectively), with
      discontinuation due to toxicity in 10% of CP patients and in 5% of AP patients.
      CONCLUSIONS: These results suggest that the long-term administration of
      omacetaxine is feasible with dose adjustments to manage toxicities and that
      omacetaxine provides a durable benefit for some patients.

PMID- 25586016
TI  - Metachronous cardiac and cerebral sarcomas: case report with focus on molecular
      findings and review of the literature.
AB  - Although multiple primary malignancies are relatively rare, they have increased
      in frequency over the last decades, partly because of advances in diagnosis and
      therapy. This report describes for the first time the case of a patient with past
      occupational exposure to asbestos and no family history of cancer who developed 2
      rare primary malignancies: a cardiac sarcoma and a gliosarcoma 11 months later.
      Molecular-cytogenetic studies did not identify common lesions to these 2 rare
      metachronous sarcomas. The gliosarcoma was associated with monosomy 10 and
      underlying PTEN monoallelic loss, which has been recurrently observed. In the
      cardiac sarcoma, MDM2 amplification and CDKN2AB/9p21 biallelic deletion suggested
      intimal sarcoma. No causal relationship was found between cardiac sarcoma and
      asbestos exposure, although MDM2 abnormalities were linked to malignant
      mesothelioma. 

PMID- 25586017
TI  - Fracture discrimination by combined bone mineral density (BMD) and
      microarchitectural texture analysis.
AB  - The use of bone mineral density (BMD) for fracture discrimination may be improved
      by considering bone microarchitecture. Texture parameters such as trabecular bone
      score (TBS) or mean Hurst parameter (H) could help to find women who are at high
      risk of fracture in the non-osteoporotic group. The purpose of this study was to
      combine BMD and microarchitectural texture parameters (spine TBS and calcaneus H)
      for the detection of osteoporotic fractures. Two hundred and fifty five women had
      a lumbar spine (LS), total hip (TH), and femoral neck (FN) DXA. Additionally,
      texture analyses were performed with TBS on spine DXA and with H on calcaneus
      radiographs. Seventy-nine women had prevalent fragility fractures. The
      association with fracture was evaluated by multivariate logistic regressions. The
      diagnostic value of each parameter alone and together was evaluated by odds
      ratios (OR). The area under curve (AUC) of the receiver operating characteristics
      (ROC) were assessed in models including BMD, H, and TBS. Women were also
      classified above and under the lowest tertile of H or TBS according to their BMD
      status. Women with prevalent fracture were older and had lower TBS, H, LS-BMD,
      and TH-BMD than women without fracture. Age-adjusted ORs were 1.66, 1.70, and
      1.93 for LS, FN, and TH-BMD, respectively. Both TBS and H remained significantly
      associated with fracture after adjustment for age and TH-BMD: OR 2.07 [1.43;
      3.05] and 1.47 [1.04; 2.11], respectively. The addition of texture parameters in
      the multivariate models didn't show a significant improvement of the ROC-AUC.
      However, women with normal or osteopenic BMD in the lowest range of TBS or H had
      significantly more fractures than women above the TBS or the H threshold. We have
      shown the potential interest of texture parameters such as TBS and H in addition
      to BMD to discriminate patients with or without osteoporotic fractures. However,
      their clinical added values should be evaluated relative to other risk factors. 

PMID- 25586018
TI  - Systematic review of seat-belt trauma to the female breast: a new diagnosis and
      management classification.
AB  - BACKGROUND: Legislation, education and technology have led to a rise in the use
      of seat belts. This has significantly reduced automobile accident-related
      mortality, but it has increased seat belt-associated injuries. The aim of this
      study was to review all publications on seat-belt injury to the female breast and
      to analyse patterns of presentation, management and outcomes. METHODS: A
      literature search was performed by two independent reviewers using the PubMed,
      Scopus and EMBASE databases. The MeSH terms included 'seat belt breast' or
      'breast traffic accident' or 'safety belt breast'. This study was supported by
      Level V evidence. RESULTS: In this review, 26 articles describing 42 patients
      were included. A total of 13 patients (31.0%) presented immediately after the
      road traffic accident (RTA) with pain, swelling, open wounds and/or haemorrhage
      of the breast. Active arterial extravasations were treated with angiographic
      embolization while wounds were mostly treated with dressings. Twenty-nine (69.0%)
      patients presented late, with a mean time of 6.77 months (3 weeks-5 years) after
      the RTA. This ranged from a palpable lump in the area of trauma to a worsening
      cleft deformity. Most late presentations were diagnosed with fat necrosis while
      five patients (17.2%) were found to have breast cancer. From this review, we
      propose a four-tier classification system that categorizes patients based on
      timing to presentation and symptoms, with recommended investigation and
      management options for each category. CONCLUSION: This is the most comprehensive
      systemic review to date of seat-belt injuries to the female breast, and our
      proposed classification may be useful in the management of such patients.

PMID- 25586019
TI  - Quality in healthcare and the contribution of patient and public involvement:
      talking the talk and walking the walk?

PMID- 25586020
TI  - A freshwater predator hit twice by the effects of warming across trophic levels.
AB  - Many ecological responses to climate change have been documented. However, due to
      indirect effects, some responses can be complex and difficult to predict. For
      example, our understanding of effects on consumers involving responses on several
      trophic levels is limited. Here, combining the knowledge of trophic interactions
      in the EU's fourth largest lake with long-term climate and catch data, we analyse
      potential drivers of change in this system's apex predator. We show that warm
      winters correlate with later poor catches of great Arctic charr (Salvelinus
      umbla), and that in recent years predator-prey cycles involving this species have
      disappeared. The likely mechanisms are trophic mismatches directly and indirectly
      affecting two stages of charr, the fry and the juveniles, respectively. Our study
      illustrates how a long-lived consumer may be subjected to double jeopardy from
      the effects of warming across trophic levels, and that a food web approach can
      aid in disentangling the chain of mechanisms responsible. 

PMID- 25586021
TI  - Streptomyces oryzae sp. nov., an endophytic actinomycete isolated from stems of
      rice plant.
AB  - An actinomycete strain S16-07(T), isolated from surface-sterilized stems of rice
      plant (Oryza sativa L.), was characterized using a polyphasic approach.
      Phylogenetic analysis of 16S rRNA gene sequences indicated affiliation of the
      strain belonged to the genus Streptomyces. The highest levels of sequence
      similarity were found with Streptomyces smyrnaeus SM3501(T) (97.7% similarity),
      S. abikoensis NBRC 13860(T) (97.6% similarity) and S. thermocarboxydovorans NBRC
      16324(T) (97.5% similarity). The cell wall of strain S16-07(T) contained LL
      diaminopimelic acid. The predominant menaquinones were MK-9(H6) and MK-9(H8).
      Phospholipids detected were phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol, hydroxy-phosphatidylethanolamine, hydroxy
      phosphatidylmonomethylethanolamine and phosphatidylinositol mannosides. The major
      cellular fatty acids were ai-C(15:0), i-C(16:0) and ai-C(17:0). The G+C content
      of strain S16-07(T) was 70.4 mol%. On the basis of the phylogeny of the isolate
      and its differences from the most closely related species, the isolate S16-07(T)
      represents a novel species for which the name S. oryzae sp. nov. is proposed. The
      type strain is S16-07(T) (=BCC 60400(T)=NBRC 109761(T)).

PMID- 25586022
TI  - In vitro evaluation of ciclopirox as an adjuvant for polymyxin B against gram
      negative bacteria.

PMID- 25586023
TI  - Sartorypyrone D: a new NADH-fumarate reductase inhibitor produced by Neosartorya
      fischeri FO-5897.

PMID- 25586024
TI  - Natural lipopeptide antibiotic tripropeptin C revitalizes and synergistically
      potentiates the activity of beta-lactams against methicillin-resistant
      Staphylococcus aureus.
AB  - Tripropeptin C (TPPC) is a natural calcium-ion-dependent lipopeptide antibiotic
      that inhibits peptidoglycan biosynthesis by binding to prenyl pyrophosphate. It
      displays very potent antimicrobial activity both in vitro and in a mouse model of
      methicillin-resistant Staphylococcus aureus (MRSA) septicemia. The combination of
      TPPC with all classes of beta-lactams tested (including penam, carbapenem, cephem
      and oxacephem) showed highly synergistic (SYN) effects against MRSA strains, but
      not against methicillin-sensitive S. aureus strains. These SYN effects were
      observed with both a checkerboard methodology and a time-kill analysis. The TPPC
      analog, bis-methyl ester-TPPC, which has neither antimicrobial activity nor the
      ability to bind prenyl pyrophosphate, also potentiated the activity of beta
      lactams. This result indicates that the mechanism of the SYN activity of TPPC is
      independent of its binding to prenyl pyrophosphate. Therefore, synergistically
      enhancing the anti-MRSA activities of TPPC and beta-lactams by combining them is
      a novel and potentially powerful therapeutic strategy for MRSA infections. 

PMID- 25586026
TI  - Roos and NACP-02 ion chamber perturbations and water-air stopping-power ratios
      for clinical electron beams for energies from 4 to 22 MeV.
AB  - Empirical fits are developed for depth-compensated wall- and cavity-replacement
      perturbations in the PTW Roos 34001 and IBA / Scanditronix NACP-02 parallel-plate
      ionisation chambers, for electron beam qualities from 4 to 22 MeV for depths up
      to approximately 1.1 * R50,D. These are based on calculations using the Monte
      Carlo radiation transport code EGSnrc and its user codes with a full simulation
      of the linac treatment head modelled using BEAMnrc. These fits are used with
      calculated restricted stopping-power ratios between air and water to match
      measured depth-dose distributions in water from an Elekta Synergy clinical linear
      accelerator at the UK National Physical Laboratory. Results compare well with
      those from recent publications and from the IPEM 2003 electron beam radiotherapy
      Code of Practice.

PMID- 25586025
TI  - Additional congeners of the macrolide neaumycin: structure revision and
      biological activity.

PMID- 25586028
TI  - Detection of Alpha-Methylacyl-CoA Racemase (AMACR), a Biomarker of Prostate
      Cancer, in Patient Blood Samples Using a Nanoparticle Electrochemical Biosensor.
AB  - Although still commonly used in clinical practice to screen and diagnose prostate
      cancer, there are numerous weaknesses of prostate-specific antigen (PSA) testing,
      including lack of specificity and the inability to distinguish between aggressive
      and indolent cancers. A promising prostate cancer biomarker, alpha-methylacyl-CoA
      racemase (AMACR), has been previously demonstrated to distinguish cancer from
      healthy and benign prostate cells with high sensitivity and specificity. However,
      no accurate clinically useful assay has been developed. This study reports the
      development of a single use, disposable biosensor for AMACR detection. Human
      blood samples were used to verify its validity, reproducibility and reliability.
      Plasma samples from 9 healthy males, 10 patients with high grade prostatic
      intraepithelial neoplasia (HGPIN), and 5 prostate cancer patients were measured
      for AMACR levels. The average AMACR levels in the prostate cancer patients was 10
      fold higher (mean(SD) = 0.077 (0.10)) than either the controls (mean(SD) = 0.005
      (0.001)) or HGPIN patients (mean(SD) = 0.004 (0.0005)). At a cutoff of between
      0.08 and 0.9, we are able to achieve 100% accuracy in separating prostate cancer
      patients from controls. Our results provide strong evidence demonstrating that
      this biosensor can perform as a reliable assay for prostate cancer detection and
      diagnosis. 

PMID- 25586029
TI  - Water-soluble electrospun nanofibers as a method for on-chip reagent storage.
AB  - This work demonstrates the ability to electrospin reagents into water-soluble
      nanofibers resulting in a stable on-chip enzyme storage format.
      Polyvinylpyrrolidone (PVP) nanofibers were spun with incorporation of the enzyme
      horseradish peroxidase (HRP). Scanning electron microscopy (SEM) of the spun
      nanofibers was used to confirm the non-woven structure which had an average
      diameter of 155 +/- 34 nm. The HRP containing fibers were tested for their change
      in activity following electrospinning and during storage. A colorimetric assay
      was used to characterize the activity of HRP by reaction with the nanofiber mats
      in a microtiter plate and monitoring the change in absorption over time.
      Immediately following electrospinning, the activity peak for the HRP decreased by
      approximately 20%. After a storage study over 280 days, 40% of the activity
      remained. In addition to activity, the fibers were observed to solubilize in the
      microfluidic chamber. The chromogenic 3,3',5,5'-tetramethylbenzidine solution
      reacted immediately with the fibers as they passed through a microfluidic
      channel. The ability to store enzymes and other reagents on-chip in a rapidly
      dispersible format could reduce the assay steps required of an operator to
      perform. 

PMID- 25586027
TI  - Using complementary acoustic and optical techniques for quantitative monitoring
      of biomolecular adsorption at interfaces.
AB  - The great wealth of different surface sensitive techniques used in biosensing,
      most of which claim to measure adsorbed mass, can at first glance look
      unnecessary. However, with each technique relying on a different transducer
      principle there is something to be gained from a comparison. In this tutorial
      review, different optical and acoustic evanescent techniques are used to
      illustrate how an understanding of the transducer principle of each technique can
      be exploited for further interpretation of hydrated and extended polymer and
      biological films. Some of the most commonly used surface sensitive biosensor
      techniques (quartz crystal microbalance, optical waveguide spectroscopy and
      surface plasmon resonance) are briefly described and five case studies are
      presented to illustrate how different biosensing techniques can and often should
      be combined. The case studies deal with representative examples of adsorption of
      protein films, polymer brushes and lipid membranes, and describe e.g., how to
      deal with strongly vs. weakly hydrated films, large conformational changes and
      ordered layers of biomolecules. The presented systems and methods are compared to
      other representative examples from the increasing literature on the subject. 

PMID- 25586030
TI  - The use of Angiotensin-I converting enzyme i/d genetic polymorphism as a
      biomarker of athletic performance in humans.
AB  - Angiotensin II is a key regulator of blood pressure and cardiovascular function
      in mammals. The conversion of angiotensin into its active form is carried out by
      Angiotensin I-Converting Enzyme (ACE). The measurement of ACE concentration in
      plasma or serum, its enzymatic activity, and the correlation between an
      insertion/deletion (I/D) genetic polymorphism of the ACE gene have been
      investigated as possible indicators of superior athletic performance in humans.
      In this context, other indicators of superior adaptation to exercise resulting in
      better athletic performance (such as ventricular hypertrophy, VO2 max, and
      competition results) were mostly used to study the association between ACE I/D
      polymorphism and improved performance. Despite the fact that the existing
      literature presents little consensus, there is sufficient scientific evidence to
      warrant further investigation on the usage of ACE activity and the I/D ACE gene
      polymorphism as biomarkers of superior athletic performance in humans of specific
      ethnicities or in athletes involved in certain sports. In this sense, a biomarker
      would be a substance or genetic component that could be measured to provide a
      degree of certainty, or an indication, of the presence of a certain trait or
      characteristic that would be beneficial to the athlete's performance.
      Difficulties in interpreting and comparing the results of scientific research on
      the topic arise from dissimilar protocols and variation in study design. This
      review aims to investigate the current literature on the use of ACE I/D
      polymorphism as a biomarker of performance in humans through the comparison of
      scientific publications. 

PMID- 25586031
TI  - Microfluidic-Based Amplification-Free Bacterial DNA Detection by
      Dielectrophoretic Concentration and Fluorescent Resonance Energy Transfer
      Assisted in Situ Hybridization (FRET-ISH).
AB  - Although real-time PCR (RT-PCR) has become a diagnostic standard for rapid
      identification of bacterial species, typical methods remain time-intensive due to
      sample preparation and amplification cycle times. The assay described in this
      work incorporates on-chip dielectrophoretic capture and concentration of
      bacterial cells, thermal lysis, cell permeabilization, and nucleic acid
      denaturation and fluorescence resonance energy transfer assisted in situ
      hybridization (FRET-ISH) species identification. Combining these techniques
      leverages the benefits of all of them, allowing identification to be accomplished
      completely on chip less than thirty minutes after receipt of sample, compared to
      multiple hours required by traditional RT-PCR and its requisite sample
      preparation. 

PMID- 25586032
TI  - An Electrochemical Immunosensor for Detection of Staphylococcus aureus Bacteria
      Based on Immobilization of Antibodies on Self-Assembled Monolayers-Functionalized
      Gold Electrode.
AB  - The detection of pathogenic bacteria remains a challenge for the struggle against
      biological weapons, nosocomial diseases, and for food safety. In this research,
      our aim was to develop an easy-to-use electrochemical immunosensor for the
      detection of pathogenic Staphylococcus aureus ATCC25923. The biosensor was
      elaborated by the immobilization of anti-S. aureus antibodies using a self
      assembled monolayer (SAMs) of 3-Mercaptopropionic acid (MPA). These molecular
      assemblies were spontaneously formed by the immersion of the substrate in an
      organic solvent containing the SAMs that can covalently bond to the gold surface.
      The functionalization of the immunosensor was characterized using two
      electrochemical techniques: cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS). Here, the analysis was performed in phosphate buffer with
      ferro/ferricyanide as the redox probe. The EIS technique was used for affinity
      assays: antibody-cell binding. A linear relationship between the increment in the
      electron transfer resistance (RCT) and the logarithmic value of S. aureus
      concentration was observed between 10 and 106 CFU/mL. The limit of detection
      (LOD) was observed at 10 CFU/mL, and the reproducibility was calculated to 8%.
      Finally, a good selectivity versus E. coli and S. epidermidis was obtained for
      our developed immunosensor demonstrating its specificity towards only S. aureus. 

PMID- 25586033
TI  - A facile inhibitor screening of hepatitis C virus NS3 protein using nanoparticle
      based RNA.
AB  - Globally, over hundreds of million people are infected with the hepatitis C
      virus: the global rate of death as a direct result of the hepatitis C virus has
      increased remarkably. For this reason, the development of efficient drug
      treatments for the biological effects of the hepatitis C virus is highly
      necessary. We have previously shown that quantum dots (QDs)-conjugated RNA
      oligonucleotide can recognize the hepatitis C virus NS3 protein specifically and
      sensitively. In this study, we elucidated that this biochip can analyze
      inhibitors to the hepatitis C virus NS3 protein using a nanoparticle-based RNA
      oligonucleotide. Among the polyphenolic compounds examined, 7,8,4'
      trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone demonstrated a remarkable
      inhibition activity on the hepatitis C virus NS3 protein. Both 7,8,4'
      trihydroxyisoflavone and 6,7,4'-trihydroxyisoflavone attenuated the binding
      affinity in a concentrated manner as evidenced by QDs conjugated RNA
      oligonucleotide. At a concentration of 0.01 MUg.mL-1, 7,8,4'-trihydroxyisoflavone
      and 6,7,4'-trihydroxyisoflavone showed more than a 30% inhibition activity of a
      nanoparticle-based RNA oligonucleotide biochip system. 

PMID- 25586034
TI  - A New Approach for Detection Improvement of the Creutzfeldt-Jakob Disorder
      through a Specific Surface Chemistry Applied onto Titration Well.
AB  - This work illustrates the enhancement of the sensitivity of the ELISA titration
      for recombinant human and native prion proteins, while reducing other non
      specific adsorptions that could increase the background signal and lead to a low
      sensitivity and false positives. It is achieved thanks to the association of
      plasma chemistry and coating with different amphiphilic molecules bearing either
      ionic charges and/or long hydrocarbon chains. The treated support by 3
      butenylamine hydrochloride improves the signal detection of recombinant protein,
      while surface modification with the 3,7-dimethylocta-2,6-dien-1-diamine
      (geranylamine) enhances the sensitivity of the native protein. Beside the surface
      chemistry effect, these different results are associated with protein
      conformation. 

PMID- 25586036
TI  - Synthesis of a functionalized polypyrrole coated electrotextile for use in
      biosensors.
AB  - An electrotextile with a biosensing focus composed of conductive polymer coated
      microfibers that contain functional attachment sites for biorecognition elements
      was developed. Experiments were conducted to select a compound with a pendant
      functional group for inclusion in the polymer, a fiber platform, and
      polymerization solvent. The effects of dopant inclusion and post-polymerization
      wash steps were also analyzed. Finally, the successful attachment of avidin,
      which was then used to capture biotin, to the electrotextile was achieved. The
      initial results show a nonwoven fiber matrix can be successfully coated in a
      conductive, functionalized polymer while still maintaining surface area and fiber
      durability. A polypropylene fiber platform with a conductive polypyrrole coating
      using iron (III) chloride as an oxidant, water as a solvent, and 5-sulfosalicylic
      acid as a dopant exhibited the best coating consistency, material durability, and
      lowest resistance. Biological attachment of avidin was achieved on the fibers
      through the inclusion of a carboxyl functional group via 3-thiopheneacetic acid
      in the monomer. The immobilized avidin was then successfully used to capture
      biotin. This was confirmed through the use of fluorescent quantum dots and
      confocal microscopy. A preliminary electrochemical experiment using avidin for
      biotin detection was conducted. This technology will be extremely useful in the
      formation of electrotextiles for use in biosensor systems. 

PMID- 25586035
TI  - Evaluating Inhibition of the Epidermal Growth Factor (EGF)-Induced Response of
      Mutant MCF10A Cells with an Acoustic Sensor.
AB  - Many cancer treatments rely on inhibition of epidermal growth factor (EGF)
      induced cellular responses. Evaluating drug effects on such responses becomes
      critical to the development of new cancer therapeutics. In this report, we have
      employed a label-free acoustic sensor, the quartz crystal microbalance with
      dissipation monitoring (QCM-D), to track the EGF-induced response of mutant
      MCF10A cells under various inhibitory conditions. We have identified a complex
      cell de-adhesion process, which can be distinctly altered by inhibitors of
      signaling pathways and cytoskeleton formation in a dose-dependent manner. The
      dose dependencies of the inhibitors provide IC50 values which are in strong
      agreement with the values reported in the literature, demonstrating the
      sensitivity and reliability of the QCM-D as a screening tool. Using
      immunofluorescence imaging, we have also verified the quantitative relationship
      between the DeltaD-response (change in energy dissipation factor) and the level
      of focal adhesions quantified with the areal density of immunostained vinculin
      under those inhibitory conditions. Such a correlation suggests that the dynamic
      restructuring of focal adhesions can be assessed based on the time-dependent
      change in DeltaD-response. Overall, this report has shown that the QCM-D has the
      potential to become an effective sensing platform for screening therapeutic
      agents that target signaling and cytoskeletal proteins. 

PMID- 25586037
TI  - Prediction of melting temperatures in fluorescence in situ hybridization (FISH)
      procedures using thermodynamic models.
AB  - The thermodynamics and kinetics of DNA hybridization, i.e. the process of self
      assembly of one, two or more complementary nucleic acid strands, has been studied
      for many years. The appearance of the nearest-neighbor model led to several
      theoretical and experimental papers on DNA thermodynamics that provide reasonably
      accurate thermodynamic information on nucleic acid duplexes and allow estimation
      of the melting temperature. Because there are no thermodynamic models
      specifically developed to predict the hybridization temperature of a probe used
      in a fluorescence in situ hybridization (FISH) procedure, the melting temperature
      is used as a reference, together with corrections for certain compounds that are
      used during FISH. However, the quantitative relation between melting and
      experimental FISH temperatures is poorly described. In this review, various
      models used to predict the melting temperature for rRNA targets, for DNA
      oligonucleotides and for nucleic acid mimics (chemically modified
      oligonucleotides), will be addressed in detail, together with a critical
      assessment of how this information should be used in FISH. 

PMID- 25586040
TI  - Obesity and pre-diabetes.

PMID- 25586038
TI  - Decrease in diversity and changes in community composition of arbuscular
      mycorrhizal fungi in roots of apple trees with increasing orchard management
      intensity across a regional scale.
AB  - Understanding which factors drive the diversity and community composition of
      arbuscular mycorrhizal fungi (AMF) is important due to the role of these soil
      micro-organisms in ecosystem functioning and current environmental threats to AMF
      biodiversity. Additionally, in agro-ecosystems, this knowledge may help to
      evaluate their use in making agriculture more sustainable. Here, we used 454
      pyrosequencing of small subunit rRNA gene amplicons to quantify AMF diversity and
      community composition in the roots of cultivated apple trees across 24 orchards
      in central Belgium. We aimed at identifying the factors (soil chemical variables,
      organic vs. conventional farming, and geographical location) that affect AMF
      diversity and community composition. In total, 110 AMF OTUs were detected, of
      which the majority belonged to the Glomeraceae (73%) and the Claroideoglomeraceae
      (19%). We show that soil characteristics and farming system, rather than the
      geographical location of the orchards, shape AMF communities on apple trees.
      Particularly, plant-available P content of the soil was associated with lower AMF
      diversity. In orchards with a lower plant-available P content of the soil (P <
      100 mg/kg soil), we also found a significantly higher AMF diversity in
      organically managed orchards as compared to conventionally managed orchards.
      Finally, the degree of nestedness of the AMF communities was related to plant
      available P and N content of the soil, pointing at a progressive loss of AMF taxa
      with increasing fertilization. Overall, we conclude that a combination of organic
      orchard management and moderate fertilization may preserve diverse AMF
      communities on apple trees and that AMF in the roots of apple trees appear not to
      be dispersal limited at the scale of central Belgium. 

PMID- 25586041
TI  - Plea for simplicity: use of waist-to-height ratio as a primary screening tool to
      assess cardiometabolic risk.

PMID- 25586042
TI  - Attendance and weight outcomes in 4754 adults referred over 6 months to a primary
      care/commercial weight management partnership scheme.
AB  - WHAT IS ALREADY KNOWN ON THIS SUBJECT: *  There is growing evidence of the
      effectiveness of commercial weight management programmes in the community. A
      recent randomized controlled trial has shown commercial providers to be more
      effective than NHS providers for weight management solutions in primary care.
      Some commercial weight management providers have established national slimming on
      referral schemes for weight management, which result on average in weight losses
      of 4-5% over a 12-week referral period. A recent randomized controlled trial of a
      similar scheme over 12 months yielded similar weight loses. Another RCT comparing
      commercial providers over 6 months showed average weight losses of ~6.6% across
      providers. WHAT THIS STUDY ADDS: *  The present study shows that when local
      primary care practitioners target resources to where they, as health
      professionals, felt they would have the most beneficial effect in their local
      communities, greater weight losses can be achieved. *  Different NHS Trusts
      extended 12-week referrals by an additional 12 weeks in a total of 4754 patients.
      *  Mean weight losses of 8.6% were achieved suggesting that local targeting of
      primary care resources can maximize returns for NHS investments in commissioning
      the services of commercial weight management organizations. SUMMARY: This project
      audited attendance and weight loss in a primary care/commercial weight management
      partnership scheme in patients who participated over 6 months. 4754 adult
      patients (575 men, 4179 women) were referred to Slimming World for 24 weekly
      sessions. Data were analysed using individual weekly weight records. Mean
      (standard deviation, SD) body mass index (BMI) change was -3.3 kg m(-2) (2.2),
      weight change -8.9 kg (6.0), percent weight change -8.6% (5.3) and number of
      sessions attended 21.3 (3.2) of 24. For patients attending at least 20 of 24
      sessions (n = 3626 or 76.3%), mean (SD) BMI change was -3.6 kg m(-2) (2.2),
      weight change -9.6 kg (6.1), percent weight change -9.3% (5.3). Weight loss was
      greater in men than women (P < 0.001). 74.5% of all patients enrolled, and 79.3%
      of patients attending 20 or more sessions achieved at least 5% weight loss. 37.3%
      of the whole population lost >=10% of their weight. Weight gain was prevented in
      96.3% of all patients referred. Referral to a commercial organization for
      community-based lifestyle intervention is a practical option for longer-term
      National Health Service weight management strategies.

PMID- 25586043
TI  - Psychological flexibility and the gains of acceptance-based treatment for post
      bariatric surgery: six-month follow-up and a test of the underlying model.
AB  - Research highlights *  Bariatric surgery is associated with dramatic weight loss.
      *  Follow-up studies show that many surgery patients continue to struggle with
      self-stigma, body dissatisfaction and emotional eating. *  To date we are aware
      of only three published randomized controlled trials evaluating psychological
      interventions in combination with bariatric surgery. *  Acceptance and Commitment
      Therapy (ACT) targets psychological flexibility: acceptance to have difficult
      feelings and thoughts, while at the same time engaging in vital healthy
      activities. *  The present study shows significant improvements in the ACT group
      as compared with (TAU) after treatment as usual at a 6-month follow-up and shows
      that the mechanism of change may be psychological flexibility. *  Results from
      this study indicate the possibility of optimizing bariatric surgery outcomes by
      adding interventions targeting psychological flexibility. SUMMARY: The current
      article presents and evaluates an Acceptance and Commitment Therapy (ACT)
      approach for obesity-related psychological struggles post-bariatric surgery. Some
      patients who have undergone bariatric surgery report loss of control over eating
      and distress concerning body figure and shape, which can affect other outcomes
      such as weight loss and quality of life post surgery. A recent randomized trial
      (n = 39) evaluating a 6-week treatment package of ACT following bariatric surgery
      found large and significant effects as compared with treatment as usual (TAU) on
      eating disordered behaviours, body dissatisfaction, psychological flexibility and
      quality of life. Though effects were found, questions remain regarding
      maintenance of outcomes and the process changes related to outcomes. The present
      study examines both the maintenance of behavioural change at a 6-month follow-up
      for the original study and the processes that may be involved in the outcomes.
      ACT led to gains in quality of life (es = 0.88) and body dissatisfaction (es =
      0.77), as compared with TAU at follow-up. Both groups improved in eating
      disordered behaviours (ACT; es = 0.86 and TAU; es = 0.55). A series of multiple
      mediator tests supported the role of enhanced psychological flexibility in the
      changes seen in body dissatisfaction, eating disordered behaviour and quality of
      life. This study provides preliminary support for the ACT treatment model in
      terms of optimizing bariatric surgery outcomes.

PMID- 25586039
TI  - Extracellular vesicle-mediated export of fungal RNA.
AB  - Extracellular vesicles (EVs) play an important role in the biology of various
      organisms, including fungi, in which they are required for the trafficking of
      molecules across the cell wall. Fungal EVs contain a complex combination of
      macromolecules, including proteins, lipids and glycans. In this work, we aimed to
      describe and characterize RNA in EV preparations from the human pathogens
      Cryptococcus neoformans, Paracoccidiodes brasiliensis and Candida albicans, and
      from the model yeast Saccharomyces cerevisiae. The EV RNA content consisted
      mostly of molecules less than 250 nt long and the reads obtained aligned with
      intergenic and intronic regions or specific positions within the mRNA. We
      identified 114 ncRNAs, among them, six small nucleolar (snoRNA), two small
      nuclear (snRNA), two ribosomal (rRNA) and one transfer (tRNA) common to all the
      species considered, together with 20 sequences with features consistent with
      miRNAs. We also observed some copurified mRNAs, as suggested by reads covering
      entire transcripts, including those involved in vesicle-mediated transport and
      metabolic pathways. We characterized for the first time RNA molecules present in
      EVs produced by fungi. Our results suggest that RNA-containing vesicles may be
      determinant for various biological processes, including cell communication and
      pathogenesis. 

PMID- 25586044
TI  - Effect of weight loss after gastric bypass surgery on thyroid function in
      euthyroid people with morbid obesity.
AB  - Obesity is positively associated with serum thyrotropin (TSH) concentrations at
      the high end of the normal range. The relationship between weight loss and
      thyroid function is less clear and studies to date have yielded inconsistent
      results. Our aim was to describe changes in thyroid function in obese people in
      relation to durable and significant weight loss after Roux-en-Y gastric bypass
      (RYGB) surgery. We recorded percentage of excess weight loss (% EWL), serum TSH
      and free thyroxine (fT4) before and median 4.5, 15 and 24 months after RYGB in 55
      euthyroid patients with morbid obesity ranging in age from 18 to 64 years in a
      retrospective cohort analysis in a university hospital in Greater Manchester.
      Mean +/- standard error preoperative weight was 135.13 +/- 4.23 kg and BMI 48.08
      +/- 1.58 kg m(-2) . Patients attained nadir %EWL of 68% by median 15 months after
      RYGB. TSH was 2.00 +/- 0.14 mU L(-1) at baseline and 2.02 +/- 0.22 mU L(-1) at 24
      months after RYGB (non-significant). Baseline fT4 was 13.46 +/- 0.28 pmol L(-1) ,
      and increased significantly to 15.14 +/- 0.55 pmol L(-1) at 24 months (P <
      0.004). In conclusion, we report that weight loss after RYGB was accompanied by
      significant increase in serum fT4 but no change in TSH concentrations. Further
      study to elucidate the effect of significant weight loss on the thyroid axis is
      required. 

PMID- 25586045
TI  - Plasma amino acid profile is associated with visceral fat accumulation in obese
      Japanese subjects.
AB  - What is already known about this subject *  Asians with metabolic complications
      associated with obesity, a low body mass index and a low waist circumference have
      a greater proportion of visceral adipose tissue for a given amount of total body
      fat compared with Europeans. *  Apparent obese humans and obese animal models
      show an elevation of branched-chain amino acid levels in plasma. *  A
      multivariate logistic regression model of plasma free amino acids has been used
      to screen for several types of cancers in clinical settings. What this study adds
      *  A specific formula incorporating six amino acid values (Ala, Gly, Glu, Trp,
      Tyr and branched-chain amino acid) was developed for discrimination of subjects
      with high visceral fat area by multivariate logistic regression analyses. *  The
      generated amino acid formula was strongly correlated with visceral fat area in
      both apparent and non-apparent obese subjects. *  Measuring plasma free amino
      acids can be used to distinguish the non-apparent visceral obesity in clinical
      settings in Asian populations. SUMMARY: Metabolic complications associated with
      obesity are becoming more common among Japanese subjects. However, visceral fat
      accumulation is not always apparent by measuring body mass index (BMI) or waist
      circumference in Asian populations because of the physiological characteristics
      particular to those ethnicities. Excess visceral fat accumulation raises the odds
      ratio for developing cardiovascular disease. Thus, high-throughput determination
      of the amount of abdominal adipose tissue is necessary. We hypothesized that
      accumulating visceral fat alters the peripheral amino acid profile and that a
      multivariate logistic regression model of plasma free amino acids can distinguish
      visceral obesity. A total of 1449 Japanese subjects (985 males and 464 females)
      who had undergone a comprehensive health screening were enrolled in this study.
      The visceral fat area was determined using computed tomography imaging, and a
      plasma free amino acid index to identify high visceral fat areas (>=100 cm(2) )
      was developed. The sensitivity and specificity values of the generated amino acid
      index were 80% and 65%, respectively. In particular, the sensitivity of the
      generated index to identify subjects with non-apparent visceral obesity (BMI < 25
      kg m(-2) ; visceral fat area >= 100 cm(2) ) was much greater than that of the
      waist circumference (73% vs. 46%, respectively). This index's high sensitivity
      and specificity may be the result of specific alterations in the patients' amino
      acid profiles, which were specifically correlated with the visceral fat areas and
      not with subcutaneous fat areas. This profile can be used as a predictor of
      elevated visceral obesity and a risk assessment tool for metabolic complications
      in Asian populations.

PMID- 25586046
TI  - Liver fat content investigated by magnetic resonance spectroscopy in obese
      children and youths included in multidisciplinary treatment.
AB  - What is already known about this subject *  Investigations of non-alcoholic fatty
      liver disease (NAFLD) by non-invasive imaging procedures have limited evidence. *
      Thirty percent of obese children are estimated to have NAFLD and implications
      for future morbidity are uncertain. What this study adds *  Many obese children
      and youths exhibit a high liver fat content as examined by magnetic resonance
      spectroscopy. *  Associations between liver fat content, anthropometry, abdominal
      adipose tissue distribution and liver enzymes are illustrated. SUMMARY: The study
      aims to investigate the degree of hepatic steatosis and associations with the
      amount of abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue
      (VAT), anthropometric data and biochemical measures of liver enzymes in children
      and youths included in obesity treatment. The study included 164 patients, aged 6
      20 years, with a body mass index (BMI) above the 90th percentile for sex and age.
      Liver fat content was measured by magnetic resonance spectroscopy (MRS). SAT and
      VAT were measured by magnetic resonance imaging. Hepatic steatosis was defined as
      liver fat content >5% (steatosis-5%) and 9% (steatosis-9%), respectively. Data on
      waist circumference (WC) and blood samples were available in 124 patients.
      Steatosis-5% and steatosis-9% were identified in 45% and 27% of the patients,
      respectively. These patients had increased SAT, VAT, BMI standard deviation
      score, WC/height ratio, alanine aminotransferase (ALT) and gamma-glutamyl
      transferase (GGT) levels. GGT, ALT and VAT were found to be independent risk
      factors of hepatic steatosis. In this study, a substantial proportion of obese
      children and youths have hepatic steatosis. Therefore, it is important to examine
      these subjects for the degree of fat in their liver. Future studies focusing on
      hepatic steatosis should consider the use of MRS in addition to blood samples.

PMID- 25586047
TI  - Cord ghrelin levels are decreased in large-for-gestational-age neonates.
AB  - Ghrelin is a growth hormone secretagogue peptide and has been recognized as an
      orexigenic factor. To investigate relationship between cord ghrelin and
      anthropometric and metabolic indices, we measured cord ghrelin in large-for
      gestational-age (LGA) and appropriate-for-gestational-age (AGA) neonates and
      examined whether cord ghrelin levels were correlated to concentrations of cord
      blood glucose, insulin, lipid and maternal ghrelin. Fifty-five singletons born at
      term and their mothers were investigated in this study. Maternal venous blood
      samples were collected before delivery. Plasma concentrations of ghrelin,
      insulin, glucose, total cholesterol, triacylglycerol (TG), low-density
      lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol were
      measured in cord blood sampled at birth. The results show that the concentrations
      of cord ghrelin are significantly lower in LGA neonates. There is a positive
      correlation between cord ghrelin levels and maternal ghrelin levels. Negative
      correlations are found between cord ghrelin levels and gestational age, the
      concentrations of cord glucose, insulin, TG and LDL. Multivariate regression
      analyses show that birth weight (r(2)  = 0.674, beta = -0.548, P < 0.001) was the
      predictor correlating with ghrelin levels. In conclusion, LGA neonates have lower
      cord ghrelin concentrations than AGA neonates. 

PMID- 25586048
TI  - Changes in body mass index and measures of abdominal obesity in Finnish adults
      between 1992 and 2007, the National FINRISK Study.
AB  - What is already known about this subject *  Recent obesity trends across the
      world in adults are mixed, varying from showing signs of levelling off to a
      continuously increasing prevalence. *  Secular trends in body mass index (BMI)
      and waist circumference may vary by sex and age. *  Relying exclusively on BMI
      data may lead to underestimate the obesity epidemic. What this study adds * 
      Adverse trends in obesity indicators have continued in Finland in the 2000s. * 
      In older men, BMI remained quite stable and in older women BMI has decreased
      since 1997. *  Steep upward trends in abdominal obesity (waist circumference and
      waist-to-height ratio, WHtR) have taken place in both men and women and in all
      age groups, especially during the past 10 years. *  The impact of BMI adjustment
      on trends in abdominal obesity varied by age such that increases in BMI-adjusted
      waist circumference and WHtR were more prominent in older age groups. SUMMARY:
      Signs that obesity trends will level off at the turn of the 21st century have
      been reported. In these studies, however, the definition of obesity has been
      based only on body mass index (BMI). We investigated obesity trends among Finnish
      adults over recent years by using BMI, waist circumference and waist-to-height
      ratio as indicators for obesity. Data were derived from the national FINRISK
      surveys, which are cross-sectional population surveys conducted at 5-year
      intervals between 1992 and 2007. Altogether, 20 551 randomly selected men and
      women aged 25-64 years participated in health examinations, where weight, height,
      and waist and hip circumferences were measured by trained nurses. Mean BMI
      increased in younger men and women (aged 25-44 years) between 1992 and 2007,
      whereas in older men, BMI remained quite stable and in older women BMI has
      decreased since 1997. Nevertheless, mean waist circumference and waist-to-height
      ratio increased in both men and women over the 15-year period. The upward trends
      took place in all age groups, especially during the past 10 years. Adverse trends
      in obesity indicators have continued in Finland in the 2000s. In particular,
      concerns are related to steep upward trends in abdominal obesity.

PMID- 25586049
TI  - Carrier density modulation in a germanium heterostructure by ferroelectric
      switching.
AB  - The development of non-volatile logic through direct coupling of spontaneous
      ferroelectric polarization with semiconductor charge carriers is nontrivial, with
      many issues, including epitaxial ferroelectric growth, demonstration of
      ferroelectric switching and measurable semiconductor modulation. Here we report a
      true ferroelectric field effect-carrier density modulation in an underlying
      Ge(001) substrate by switching of the ferroelectric polarization in epitaxial c
      axis-oriented BaTiO3 grown by molecular beam epitaxy. Using the density
      functional theory, we demonstrate that switching of BaTiO3 polarization results
      in a large electric potential change in Ge. Aberration-corrected electron
      microscopy confirms BaTiO3 tetragonality and the absence of any low-permittivity
      interlayer at the interface with Ge. The non-volatile, switchable nature of the
      single-domain out-of-plane ferroelectric polarization of BaTiO3 is confirmed
      using piezoelectric force microscopy. The effect of the polarization switching on
      the conductivity of the underlying Ge is measured using microwave impedance
      microscopy, clearly demonstrating a ferroelectric field effect. 

PMID- 25586050
TI  - Changing water affinity from hydrophobic to hydrophilic in hydrophobic channels.
AB  - The behavior of water at hydrophobic interfaces can play a significant role in
      determining chemical reaction outcomes and physical properties. Carbon nanotubes
      and aluminophosphate materials have one-dimensional hydrophobic channels, which
      are entirely surrounded by hydrophobic interfaces. Unique water behavior was
      observed in such hydrophobic channels. In this article, changes in the water
      affinity in one-dimensional hydrophobic channels were assessed using water vapor
      adsorption isotherms at 303 K and grand canonical Monte Carlo simulations.
      Hydrophobic behavior of water adsorbed in channels wider than 3 nm was observed
      for both adsorption and desorption processes, owing to the hydrophobic
      environment. However, water showed hydrophilic properties in both adsorption and
      desorption processes in channels narrower than 1 nm. In intermediate-sized
      channels, the hydrophobic properties of water during the adsorption process were
      seen to transition to hydrophilic behavior during the desorption process.
      Hydrophilic properties in the narrow channels for both adsorption and desorption
      processes are a result of the relatively strong water-channel interactions (10-15
      kJ mol(-1)). In the 2-3 nm channels, the water-channel interaction energy of 4-5
      kJ mol(-1) was comparable to the thermal translational energy. The cohesive water
      interaction was approximately 35 kJ mol(-1), which was larger than the others.
      Thus, the water affinity change in the 2-3 nm channels for the adsorption and
      desorption processes was attributed to weak water-channel interactions and strong
      cohesive interactions. These results are inherently important to control the
      properties of water in hydrophobic environments. 

PMID- 25586051
TI  - The impact of commonly used air filters in eliminating the exposure to secondhand
      smoke constituents.
AB  - Exposure to secondhand tobacco smoke (SHS) also known as environmental tobacco
      smoke (ETS) has been well established scientifically as a human health hazard.
      Despite this and warnings from health agencies, concerns over the economic impact
      of smoke-free bans have limited political resolve to enact these regulations.
      Arguments against smoke-free bans include the contention that air filters can
      eliminate the health risks from SHS exposure. In this study, we assessed the
      effectiveness of air filters (MERV 4 and MERV 8) commonly used in homes and
      businesses in reducing the concentrations of total suspended particulates, fine
      particles and carbon monoxide from SHS as a measure of their potential to reduce
      the toxicity associated with SHS exposure. Our results demonstrate that these
      filters are not effective at reducing carbon monoxide levels or PM 2.5, which
      have been correlated with human health toxicity/disease. Thus, our findings, from
      a public health perspective, do not support the use of common air filters as a
      viable alternative to smoke-free bans. 

PMID- 25586052
TI  - CYP3A5 regulates prostate cancer cell growth by facilitating nuclear
      translocation of AR.
AB  - BACKGROUND: The central role of androgen receptor (AR) signaling is established
      in prostate cancer growth and progression. We propose CYP3A5 is part of a
      feedback loop that modulates the sensitivity of AR to androgen exposure. The
      purpose of this study is to elucidate the mechanism of regulation of AR
      expression by CYP3A5. METHODS: To identify the role of CYP3A5 in regulating AR
      signaling, CYP3A5 protein expression was inhibited using CYP3A5 siRNA and
      azamulin. Both cell fractionation and immunocytochemical approaches in
      combination with dihydrotestosterone (DHT) and R1881 treatment were used to
      evaluate changes in AR nuclear translocation. RESULTS: CYP3A5 siRNA blocked
      growth of LNCaP and C4-2 cells by 30-60% (P <= 0.005). Azamulin, a CYP3A
      pharmacologic inhibitor, reduced the growth of LNCaP, C4-2 and 22RV1 lines by ~
      40% (P <= 0.005). CYP3A5 siRNA inhibited growth in response to DHT and R1881
      treatment in LNCaP and C4-2 by decreasing nuclear AR localization and resulting
      in diminished PSA and TMPRSS2 expression. Decreased AR nuclear localization
      resulting from CYP3A5 inhibition resulted in growth inhibition comparable to IC60
      and IC40 of bicalutamide in LNCaP and C4-2 cell lines. Conversely, the CYP3A
      inducer rifampicin enhanced AR nuclear localization. CONCLUSION: As CYP3A5
      regulates the nuclear translocation of AR; co-targeting CYP3A5 may provide a
      novel strategy for enhancing the efficacy of androgen deprivation therapy.
      Consequentially, these data suggest that concomitant medications may impact
      androgen deprivation therapy's efficacy.

PMID- 25586053
TI  - Baicalin inhibits the expression of monocyte chemoattractant protein-1 and
      interleukin-6 in the kidneys of apolipoprotein E-knockout mice fed a high
      cholesterol diet.
AB  - Hyperlipidemia is considered an independent risk factor for renal dysfunction and
      induces a significant increase in the expression of inflammatory mediators, which
      can be used to evaluate the degree of renal injury. Baicalin is widely used in
      traditional Chinese herbal medicine and has multiple pharmacological effects. The
      present study investigated whether baicalin can attenuate the expression of
      vascular cell adhesion molecule 1 (VCAM-1) via a reduction in the expression of
      monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in the kidney
      of apolipoprotein E (ApoE)-knockout (KO) mice fed a high cholesterol diet. These
      mice were used as a model of atherosclerosis and were treated with baicalin (100
      mg/kg/day) daily by gavage for a period of 12 weeks. By contrast, wild-type male
      C57BL/6J mice were fed a standard diet. Blood samples were obtained from the
      angular veins of the mice to measure the total cholesterol (TC) and the
      expression levels of VCAM-1, MCP-1 and IL-6 in the kidney tissues of the mice
      were analyzed using reverse transcription quantitative polymerase chain reaction
      and western blot analysis. Following oral administration of baicalin, no
      significant difference was observed in the TC in the baicalin group compared with
      the high cholesterol diet control group. The TC was significantly higher in the
      AopE-KO mice compared with the wild-type male C57BL/6J mice. The expression
      levels of VCAM-1, MCP-1 and IL-6 in the kidney tissues of the baicalin group were
      lower compared with those in the high cholesterol diet control group. The results
      suggested that baicalin decreased the expression levels of pro-inflammatory
      mediators and prevented kidney dysfunction in the ApoE-KO mice fed a high
      cholesterol diet.

PMID- 25586054
TI  - Capacity for scaling up nutrition: a focus on pre-service training in West Africa
      and a Ghanaian case study.
AB  - The 2013 Lancet series on maternal and child nutrition is identified and
      advocated for improved institutional and human capacity in nutrition towards
      scaling up nutrition (SUN) in countries with high stunting rates. Of the fifty
      four countries with high burden of child undernutrition who have committed to the
      SUN movement, thirty-six are in Africa. In the present paper, the academic
      platform of the SUN movement in Ghana presents an overview of nutrition pre
      service capacity in West Africa with a focus on Ghana. The present paper is based
      on the findings of a sub-region-wide assessment of degree programmes in nutrition
      in West Africa, plus another report on pre-service nutrition capacity in diploma
      awarding nursing and nutrition programmes in Ghana. Although there is inadequate
      evidence on pre-service nutrition training in the sub-region, the two reports
      provide useful evidence for action, including inadequate number and distribution
      of pre-service nutrition training programmes, low nutrition graduate output, poor
      quality of the programme curriculum and instruction, and sub-optimal capital
      investment. The present paper calls for urgent action to improve pre-service
      nutrition capacity building as a critical step towards SUN in West Africa. 

PMID- 25586055
TI  - Ligation driven (19)F relaxation enhancement in self-assembled Ln(III) complexes.
AB  - Strong bidentate ligation between a fluorinated isophthalate and binuclear
      lanthanide-DO3A species yields a new class of (19)F NMR agent with very high
      nuclear relaxation rates at physiologically-relevant pH. 

PMID- 25586056
TI  - Bcl2L12 with a BH3-like domain in regulating apoptosis and TMZ-induced autophagy:
      a prospective combination of ABT-737 and TMZ for treating glioma.
AB  - Bcl2L12 as a new member of the Bcl2 family, which contains a BH2 domain and
      shares a lower amino acid similarity with other Bcl2 family proteins. Bcl2L12 is
      reported to be involved in apoptosis regulation, but this role remains
      controversial in different cancer type. Temozolomide (TMZ) is currently used to
      intervene glioma multiforme (GBM), but an acquired chemotherapeutic resistance
      maybe occurred due to undesired autophagy. Previous studies uncovered that
      Bcl2L12 may interact with Bcl-xL and may harbor a BH3-like domain. Therefore, we
      investigated whether this BH3-like domain is responsible for the Bcl2L12 anti
      apoptotic property. Moreover, we tested whether ABT-737, a BH3 mimetic agent, can
      be combined with TMZ to treat GBM. We aligned Bcl2L12 with Bcl2 family members,
      compared interacting pattern of BH3 domain and their protein 3D structure. We
      identified that Bcl2L12 interacts with Bcl-xL and Bcl2 in yeast two-hybrid
      system. Bcl2L12192-220 was a minimal region for Bcl2L12-Bcl-xL interaction. Five
      point mutations with respect to hydrophobic and charge residues were generated to
      test whether they are the key residue of BH3-like domain. Our data showed that
      both h1 (L213) and h2 residue (L217) are essential for Bcl2L12 interacting with
      Bcl2 family proteins. Ectopically expressed h1 or h2 mutant in U87MG cell line
      resulted in reactivation of cleaved-PARP, caspase-3 and cytochrome c releasing
      compared to Bcl2L12 wt group. Implementing ABT-737 combined with TMZ provided a
      superior effect on apoptosis induction in Bcl2L12 wt group, which effectively
      reactivated apoptotic markers. Altogether, our findings indicated that Bcl2L12
      retains a BH3-like domain, which is important for the Bcl2L12 anti-apoptotic
      property and TMZ-induced autophagy. Our results basically support the idea of
      using ABT-737 to counteract the anti-apoptotic role of Bcl2L12 and sensitize drug
      response of the GBM cells to TMZ.

PMID- 25586057
TI  - Adherence to surveillance guidelines after removal of colorectal adenomas: a
      large, community-based study.
AB  - OBJECTIVE: To determine adherence to recommended surveillance intervals in
      clinical practice. DESIGN: 2997 successive patients with a first adenoma
      diagnosis (57% male, mean age 59 years) from 10 hospitals, who underwent
      colonoscopy between 1998 and 2002, were identified via Pathologisch Anatomisch
      Landelijk Geautomatiseerd Archief: Dutch Pathology Registry. Their medical
      records were reviewed until 1 December 2008. Time to and findings at first
      surveillance colonoscopy were assessed. A surveillance colonoscopy occurring
      within +/- 3 months of a 1-year recommended interval and +/- 6 months of a
      recommended interval of 2 years or longer was considered appropriate. The
      analysis was stratified by period per change in guideline (before 2002: 2-3 years
      for patients with 1 adenoma, annually otherwise; in 2002: 6 years for 1-2
      adenomas, 3 years otherwise). We also assessed differences in adenoma and
      colorectal cancer recurrence rates by surveillance timing. RESULTS: Surveillance
      was inappropriate in 76% and 89% of patients diagnosed before 2002 and in 2002,
      respectively. Patients eligible under the pre-2002 guideline mainly received
      surveillance too late or were absent (57% of cases). For patients eligible under
      the 2002 guideline surveillance occurred mainly too early (48%). The rate of
      advanced neoplasia at surveillance was higher in patients with delayed
      surveillance compared with those with too early or appropriate timed surveillance
      (8% vs 4-5%, p<0.01). CONCLUSIONS: There is much room for improving surveillance
      practice. Less than 25% of patients with adenoma receive appropriate
      surveillance. Such practice seriously hampers the effectiveness and efficiency of
      surveillance, as too early surveillance poses a considerable burden on available
      resources while delayed surveillance is associated with an increased rate of
      advanced adenoma and especially colorectal cancer.

PMID- 25586058
TI  - Baseline quantitative hepatitis B core antibody titre alone strongly predicts
      HBeAg seroconversion across chronic hepatitis B patients treated with
      peginterferon or nucleos(t)ide analogues.
AB  - OBJECTIVE: The investigation regarding the clinical significance of quantitative
      hepatitis B core antibody (anti-HBc) during chronic hepatitis B (CHB) treatment
      is limited. The aim of this study was to determine the performance of anti-HBc as
      a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive
      CHB patients treated with peginterferon (Peg-IFN) or nucleos(t)ide analogues
      (NUCs), respectively. DESIGN: This was a retrospective cohort study consisting of
      231 and 560 patients enrolled in two phase IV, multicentre, randomised,
      controlled trials treated with Peg-IFN or NUC-based therapy for up to 2 years,
      respectively. Quantitative anti-HBc evaluation was conducted for all the
      available samples in the two trials by using a newly developed double-sandwich
      anti-HBc immunoassay. RESULTS: At the end of trials, 99 (42.9%) and 137 (24.5%)
      patients achieved HBeAg seroconversion in the Peg-IFN and NUC cohorts,
      respectively. We defined 4.4 log10 IU/mL, with a maximum sum of sensitivity and
      specificity, as the optimal cut-off value of baseline anti-HBc level to predict
      HBeAg seroconversion for both Peg-IFN and NUC. Patients with baseline anti-HBc
      >=4.4 log10 IU/mL and baseline HBV DNA <9 log10 copies/mL had 65.8% (50/76) and
      37.1% (52/140) rates of HBeAg seroconversion in the Peg-IFN and NUC cohorts,
      respectively. In pooled analysis, other than treatment strategy, the baseline
      anti-HBc level was the best independent predictor for HBeAg seroconversion (OR
      2.178; 95% CI 1.577 to 3.009; p<0.001). CONCLUSIONS: Baseline anti-HBc titre is a
      useful predictor of Peg-IFN and NUC therapy efficacy in HBeAg-positive CHB
      patients, which could be used for optimising the antiviral therapy of CHB.

PMID- 25586059
TI  - FAM83B is a novel biomarker for diagnosis and prognosis of lung squamous cell
      carcinoma.
AB  - Personalized therapy for non-small cell lung cancer (NSCLC), particularly lung
      adenocarcinoma, has recently been significantly improved by the discovery of
      various molecular targets. However, this has not been the case for lung squamous
      cell carcinoma (SCC). In the present study, we identified the family with
      sequence similarity 83, member B (FAM83B) as a candidate marker for SCC through a
      comprehensive gene expression analysis and examined its correlations with various
      clinicopathological factors. The subjects of this study consisted of 215 patients
      with NSCLC who underwent complete resection from 2005 to 2011 at the Fukushima
      Medical University Hospital (Fukushima, Japan). They included 102 patients with
      adenocarcinoma and 113 with SCC. FAM83B expression was first examined in some of
      the samples by gene expression analysis and western blotting, and then all
      clinical specimens were evaluated by immunohistochemistry (IHC). The relationship
      between the quantitative values for IHC and clinicopathological factors was
      statistically analyzed. The results showed that FAM83B mRNA expression was
      significantly higher in SCC than in normal lung or adenocarcinoma (P<0.0001).
      Immunoblot analysis also confirmed this trend. Specimens containing >10% positive
      area for FAM83B were judged as 'positive'; 94.3% (107/113) of SCC and 14.7%
      (15/102) of adenocarcinoma were positive. Patients were divided into two
      subgroups according to expression (54 high-expression and 53 low-expression
      patients); the high-expression group was associated with a better disease-free
      survival (DFS) rate (P=0.042, log-rank test). In conclusion, FAM83B may be a
      reliable diagnostic and prognostic biomarker for SCC. Detailed analyses of FAM83B
      function in lung cancer are required to understand how its expression is
      associated with better prognosis in SCC.

PMID- 25586060
TI  - Designer Self-Assemble Peptides Maximize the Therapeutic Benefits of Neural Stem
      Cell Transplantation for Alzheimer's Disease via Enhancing Neuron Differentiation
      and Paracrine Action.
AB  - The neuropathological hallmarks of Alzheimer's disease (AD) include the presence
      of extracellular amyloid-beta peptide (Abeta) in the form of amyloid plaques and
      neuronal loss. Neural stem cell (NSC) is being scrutinized as a promising cell
      replacement therapy for various neurodegenerative diseases. However, the
      unfavorable niche at the site of degenerative disease is hostile to the survival
      and differentiation of transplanted cells. Here, we undertook in vitro and in
      vivo works to examine whether a designer self-assemble peptide (DSP), which
      contains one functional domain Tyr-Ile-Gly-Ser-Arg (YIGSR) derived from laminin,
      promotes the survival and neuronal differentiation of NSC and behavioral
      improvement. We found that DSP could undergo spontaneous assembly into well
      ordered nanofibers, and it not only facilitated the cell viability in normal
      culture condition, but also decreased the number of apoptotic cells induced by
      Abeta in vitro. NSC seeded in DSP showed much more neuronal differentiation than
      that seeded in self-assemble peptide (SP) or alone. In the AD model, NSC
      transplantation in DSP-treated AD rats demonstrated much more obvious cognitive
      rescue with restoration of learning/memory function compared with NSC
      transplantation in SP, NSC alone, or DSP alone treated ones. Interestingly, DSP
      enhanced the survival and neuronal differentiation of transplanted NSC. Apoptosis
      levels in the CA1 region and Abeta level in the hippocampus were significantly
      decreased in the group of NSC transplantation in DSP. Moreover, synaptic
      function, indicated by the expression of pre-synaptic protein synapsin-1, was
      restored and the secretion of anti-inflammatory and neurotrophic factors were
      increased, such as IL-10, brain-derived neurotrophic factor (BDNF), ciliary
      neurotrophic factor (CNTF), and insulin-like growth factor 1 (IGF-1), while the
      expression of pro-inflammatory factors were decreased, such as TNF-alpha and IL
      1beta. These data firstly unveiled that the biomaterial DSP can maximize the
      therapeutic benefits of NSC transplantation for AD through improving the survival
      and differentiation of transplanted stem cells and promoting the effects of
      neuroprotection, anti-neuroinflammatory and paracrine action. Our results may
      have important clinical implications for the design of future NSC-based
      strategies using the biomaterials for various neurodegenerative diseases
      including AD. 

PMID- 25586064
TI  - The combustion behavior of large scale lithium titanate battery.
AB  - Safety problem is always a big obstacle for lithium battery marching to large
      scale application. However, the knowledge on the battery combustion behavior is
      limited. To investigate the combustion behavior of large scale lithium battery,
      three 50 Ah Li(Ni(x)Co(y)Mn(z))O2/Li(4)Ti(5)O(12) batteries under different state
      of charge (SOC) were heated to fire. The flame size variation is depicted to
      analyze the combustion behavior directly. The mass loss rate, temperature and
      heat release rate are used to analyze the combustion behavior in reaction way
      deeply. Based on the phenomenon, the combustion process is divided into three
      basic stages, even more complicated at higher SOC with sudden smoke flow ejected.
      The reason is that a phase change occurs in Li(Ni(x)Co(y)Mn(z))O2 material from
      layer structure to spinel structure. The critical temperatures of ignition are at
      112-121  degrees C on anode tab and 139 to 147  degrees C on upper surface for
      all cells. But the heating time and combustion time become shorter with the
      ascending of SOC. The results indicate that the battery fire hazard increases
      with the SOC. It is analyzed that the internal short and the Li(+) distribution
      are the main causes that lead to the difference.

PMID- 25586063
TI  - Nonparametric inference in hidden Markov models using P-splines.
AB  - Hidden Markov models (HMMs) are flexible time series models in which the
      distribution of the observations depends on unobserved serially correlated
      states. The state-dependent distributions in HMMs are usually taken from some
      class of parametrically specified distributions. The choice of this class can be
      difficult, and an unfortunate choice can have serious consequences for example on
      state estimates, and more generally on the resulting model complexity and
      interpretation. We demonstrate these practical issues in a real data application
      concerned with vertical speeds of a diving beaked whale, where we demonstrate
      that parametric approaches can easily lead to overly complex state processes,
      impeding meaningful biological inference. In contrast, for the dive data, HMMs
      with nonparametrically estimated state-dependent distributions are much more
      parsimonious in terms of the number of states and easier to interpret, while
      fitting the data equally well. Our nonparametric estimation approach is based on
      the idea of representing the densities of the state-dependent distributions as
      linear combinations of a large number of standardized B-spline basis functions,
      imposing a penalty term on non-smoothness in order to maintain a good balance
      between goodness-of-fit and smoothness. 

PMID- 25586061
TI  - Glutamate Transporters/Na(+), K(+)-ATPase Involving in the Neuroprotective Effect
      as a Potential Regulatory Target of Glutamate Uptake.
AB  - The glutamate (Glu) transporters GLAST and GLT-1, as the two most important
      transporters in brain tissue, transport Glu from the extracellular space into the
      cell protecting against Glu toxicity. Furthermore, GLAST and GLT-1 are sodium
      dependent Glu transporters (GluTs) that rely on sodium and potassium gradients
      generated principally by Na(+), K(+)-ATPase to generate ion gradients that drive
      Glu uptake. There is an interaction between Na(+), K(+)-ATPase and GluTs to
      modulate Glu uptake, and Na(+), K(+)-ATPase alpha, beta or gamma subunit can be
      directly coupled to GluTs, co-localizing with GLAST or GLT-1 in vivo to form a
      macromolecular complex and operate as a functional unit to regulate glutamatergic
      neurotransmission. Therefore, GluTs/Na(+), K(+)-ATPase may be involved in the
      neuroprotective effect as a potential regulatory target of Glu uptake in
      neurodegenerative diseases induced by Glu-mediated neurotoxicity as the final
      common pathway. 

PMID- 25586062
TI  - Effects of hnRNP A2/B1 Knockdown on Inhibition of Glioblastoma Cell Invasion,
      Growth and Survival.
AB  - Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) plays an important
      role in influence of pre-messenger RNA (pre-mRNA) processing and mRNA metabolism
      and transportation in cells. Increasing evidence indicates that hnRNP A2/B1
      played an important role in development and progression of various human cancers.
      Forty cases of normal and human glioma tissue samples were analyzed using
      immunohistochemistry to reveal the expression of hnRNP A2/B1 protein in the
      samples. Then, knockdown of hnRNP A2/B1 expression induced by RNA interference
      (RNAi) method was used to analyze the role of hnRNP A2/B1 in glioblastoma cell
      viability, adhesion, migration, invasion, and chemoresistance for temozolomide
      (TMZ). The data showed that hnRNP A2/B1 protein was overexpressed in glioma
      tissue specimens and associated with advanced glioma grades. Knockdown of hnRNP
      A2/B1 could reduce glioblastoma cell viability, adhesion, migration, invasion,
      and chemoresistance for TMZ capacity, but induced tumor cells to apoptosis and
      reactive oxygen species (ROS) generation in glioma U251 and SHG44 cells.
      Molecularly, hnRNP A2/B1 knockdown reduced expression of phospho-STAT3 and MMP-2.
      Detection of hnRNP A2/B1 expression may be useful as a biomarker for prediction
      of glioma progression and knockdown of hnRNP A2/B1 expression as a novel strategy
      in future control of glioblastoma in clinic. 

PMID- 25586065
TI  - Predictors of diagnostic interval and associations with outcome in acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Little is known about diagnostic interval lengths in childhood
      cancer, their predictors or impact upon survival. To date, studies have relied on
      questionnaires or chart abstraction. We aimed to construct and validate a
      diagnostic interval measure using health services data among children with acute
      lymphoblastic leukemia (ALL) in order to determine predictors of prolonged
      intervals and associations with event-free survival (EFS). PROCEDURE: All
      children with ALL diagnosed 1995-2011 (N = 1,541) in Ontario, Canada were linked
      to population-based health administrative databases. Healthcare claims prior to
      diagnosis were used to define healthcare episodes. Diagnostic intervals (time
      between first episode with diagnostic code a priori classified as consistent with
      underlying ALL, and diagnosis) were validated by correlation with a chart
      abstraction-based measure. RESULTS: Intervals were generally short (median 2
      days, IQR 1-3). Predictors of longer intervals included having general primary
      care physicians versus pediatricians (odds ratio 1.60, 95%CI 1.04-2.47; P =
      0.03). While prolonged diagnostic intervals were associated with superior EFS
      (hazard ratio 0.71, 95%CI 0.52-0.98; P = 0.04), this was explained by confounding
      by disease biology. CONCLUSIONS: Health administrative data can be used to
      measure diagnostic intervals in ALL and potentially other pediatric malignant and
      non-malignant diseases. Diagnostic intervals were short and a marker of disease
      severity rather than independent predictors of outcome. These findings may be
      used to address caregiver guilt and caution against "early diagnosis" benchmarks
      not based in evidence. Future studies should examine the impact of diagnostic
      interval length in other conditions, but should account for potential confounding
      by disease severity.

PMID- 25586066
TI  - Gr33a modulates Drosophila male courtship preference.
AB  - In any gamogenetic species, attraction between individuals of the opposite sex
      promotes reproductive success that guarantees their thriving. Consequently, mate
      determination between two sexes is effortless for an animal. However, choosing a
      spouse from numerous attractive partners of the opposite sex needs deliberation.
      In Drosophila melanogaster, both younger virgin females and older ones are
      equally liked options to males; nevertheless, when given options, males prefer
      younger females to older ones. Non-volatile cuticular hydrocarbons, considered as
      major pheromones in Drosophila, constitute females' sexual attraction that act
      through males' gustatory receptors (Grs) to elicit male courtship. To date, only
      a few putative Grs are known to play roles in male courtship. Here we report that
      loss of Gr33a function or abrogating the activity of Gr33a neurons does not
      disrupt male-female courtship, but eliminates males' preference for younger
      mates. Furthermore, ectopic expression of human amyloid precursor protein (APP)
      in Gr33a neurons abolishes males' preference behavior. Such function of APP is
      mediated by the transcription factor forkhead box O (dFoxO). These results not
      only provide mechanistic insights into Drosophila male courtship preference, but
      also establish a novel Drosophila model for Alzheimer's disease (AD). 

PMID- 25586067
TI  - Enhanced differentiation of osteoblastic cells on novel chitosan/beta-1,3
      glucan/bioceramic scaffolds for bone tissue regeneration.
AB  - Bone scaffolds for regenerative medicine applications should have the ability to
      promote adhesion, proliferation and differentiation of osteoblast cells.
      Osteoconductive, osteoinductive and osteopromotive properties of the material are
      essential for rapid bone regeneration and new bone formation. In this study, the
      osteogenic potential of two novel tri-component scaffolds composed of krill
      chitosan, bacterial beta-1,3-glucan and bioceramics (HAp or a mix of HAp/beta-TCP
      granules) was investigated. The typical markers of the first (type I collagen),
      second (bone alkaline phosphatase) and third stages (osteocalcin) of the
      osteoblast differentiation process were evaluated during in vitro
      experimentation. The study was carried out using three various osteoblastic cell
      lines (normal human fetal osteoblast cells hFOB 1.19, human osteoblast-like cells
      derived from osteosarcoma Saos-2 and mouse calvarial preosteoblast cells MC3T3-E1
      Subclone 4). The bone alkaline phosphatase (bALP) and osteocalcin (OC) were
      determined quantitatively using enzyme-linked immunosorbent assays, and type I
      collagen (Col I) was evaluated qualitatively using the direct immunofluorescence
      (DIF) method. The data obtained clearly prove that novel scaffolds have the
      ability to increase bALP activity, to enhance extracellular matrix synthesis (Col
      I and OC) and to induce mineralized nodule formation during osteogenic
      differentiation. In conclusion, novel tri-component materials have
      osteoconductive and osteopromotive properties, and thus are promising materials
      in bone tissue engineering applications to accelerate the bone regeneration
      process. 

PMID- 25586069
TI  - Total synthesis of vinblastine, related natural products, and key analogues and
      development of inspired methodology suitable for the systematic study of their
      structure-function properties.
AB  - Biologically active natural products composed of fascinatingly complex structures
      are often regarded as not amenable to traditional systematic structure-function
      studies enlisted in medicinal chemistry for the optimization of their properties
      beyond what might be accomplished by semisynthetic modification. Herein, we
      summarize our recent studies on the Vinca alkaloids vinblastine and vincristine,
      often considered as prototypical members of such natural products, that not only
      inspired the development of powerful new synthetic methodology designed to
      expedite their total synthesis but have subsequently led to the discovery of
      several distinct classes of new, more potent, and previously inaccessible
      analogues. With use of the newly developed methodology and in addition to ongoing
      efforts to systematically define the importance of each embedded structural
      feature of vinblastine, two classes of analogues already have been discovered
      that enhance the potency of the natural products >10-fold. In one instance,
      remarkable progress has also been made on the refractory problem of reducing Pgp
      transport responsible for clinical resistance with a series of derivatives made
      accessible only using the newly developed synthetic methodology. Unlike the
      removal of vinblastine structural features or substituents, which typically has a
      detrimental impact, the additions of new structural features have been found that
      can enhance target tubulin binding affinity and functional activity while
      simultaneously disrupting Pgp binding, transport, and functional resistance.
      Already analogues are in hand that are deserving of full preclinical development,
      and it is a tribute to the advances in organic synthesis that they are readily
      accessible even on a natural product of a complexity once thought refractory to
      such an approach. 

PMID- 25586071
TI  - The current state of academic centers for interprofessional education.
AB  - Team-based interprofessional practice plays a central role in new models of care
      delivery. However, training health professionals for interprofessional practice
      remains a challenge. Centers for Interprofessional Education (IPE) exist at many
      academic institutions but have had limited success. The authors conducted
      telephone interviews with 12 leaders of academic centers for IPE, identified
      through a key informant method. Qualitative analysis of interview notes for
      common themes of barriers, successes, and insights. Most IPE centers in the US
      are small, underfunded, with no substantial staff and faculty support. Grant
      funding gives legitimacy, but sustainability is a major concern. Most have had
      success with limited educational efforts at coordinating classes, single-day
      events, and learning activities. While IPE centers have support from
      institutional leadership, they continue to face major challenges in transforming
      the scope and content of health professional training in their institutions. 

PMID- 25586068
TI  - [Parkinson's disease and psychoses].
AB  - Psychotic symptoms are common in Parkinson's disease (PD) and are associated with
      increased disability, worsened quality of life, and poor long-term prognosis. In
      this article, clinical features, hypotheses on pathogenesis, and current
      treatment strategies for Parkinson's disease psychosis (PDP) are reviewed.
      According to epidemiological studies, the prevalence of PDP is between 20 to 40
      %. Complex visual hallucinations are the most common psychotic symptoms and are
      present in 17-72 % of the patients. Other sensory disturbances encompass tactile
      hallucinations and minor hallucinatory phenomena, such as sense of presence and
      visual illusions. Hallucinations are often accompanied by delusions, whose most
      frequent themes are persecution and jealousy. The pathophysiology of PDP remains
      unclear. Different factors have been implicated, including Levo-dopa and
      dopaminergic medications, neurotransmitter imbalances, neuroanatomic alterations,
      abnormal visuospatial processes, and genetic predisposition. The first-line
      strategy in the treatment of persistent and problematic PDP is represented by
      reduction in anti-PD medications. Second-generation antipsychotics are the
      treatment of choice, with clozapine being demonstrated as the most effective and
      tolerable drug for PD patients. 

PMID- 25586074
TI  - Long-term outcome after selective dorsal rhizotomy in children with spastic
      cerebral palsy.
AB  - PURPOSE: The purpose of this study is to evaluate long-term outcomes after
      selective dorsal rhizotomy (SDR) for children with spastic cerebral palsy.
      METHODS: This is a retrospective review of a prospective database of patients who
      underwent SDR at British Columbia Children's Hospital. Hip adductor spasticity,
      hip range of motion (ROM), quadriceps strength, and motor function were assessed
      pre-operatively, at 6 months to 5 years and more than 10 years postoperatively.
      Patients were stratified by Gross Motor Function Classification System (GMFCS)
      level into group 1 (GMFCS II and III) and group 2 (GMFCS IV and V). RESULTS:
      Forty-four patients, with mean age at SDR of 4.5 years (range 2.9-7.7), were
      followed for a mean 14.4 years. Spasticity (Modified Ashworth Scale) decreased
      1.5 (p < 0.0001) by early postoperative evaluation with further decrease at late
      evaluation of 0.8 (p < 0.0001). Early improvement in hip ROM of 13.7 degrees (p <
      0.0001) was not sustained at late assessment. Motor function improved in both
      groups at early assessment but was only sustained in group 1. Group 1 increased
      10.0 points (p < 0.0001) at early evaluation with subsequent decrease of 3.5,
      resulting in an overall increase of 6.6 (p = 0.04) from baseline. Group 2
      patients had an initial increase of 8.3 [2.0, 14.6] (p = 0.01) but then declined
      to 4.9 below baseline (p = 0.3). CONCLUSIONS: SDR yields durable reduction in
      spasticity after 10 years. Early improvements in motor function are present, but
      at long-term follow-up, these improvements were attenuated in GMFCS II and III
      and were not sustained in GMFCS IV and V.

PMID- 25586070
TI  - Quality of life attenuates age-related decline in functional status of older
      adults.
AB  - PURPOSE: In the present study, we aimed to examine the total and moderating
      effects of needs-satisfaction-driven quality-of-life (QoL) measure on age-related
      change in functional status. METHODS: Participants in the Survey of Health and
      Retirement in Europe (N = 18,781 at Wave 1) completed a measure of QoL (CASP-12)
      at baseline and reported their functional status across subsequent three waves
      using activities of daily living (ADL), instrumental activities of daily living
      (IADL), and functional limitation indices. RESULTS: Growth-curve model estimates
      revealed that aged individuals with lower QoL scores at baseline had a steeper
      increase in disability deficits accumulation and functional limitation
      progression than their counterparts with a higher sense of QoL. The effects were
      more pronounced in ADL and IADL disability scales in which QoL moderated both
      linear and quadratic age-related changes. CONCLUSIONS: Higher QoL attenuates
      processes of functional decline in late adulthood. Practitioners may seek
      strategies for improving and enhancing patients' QoL, as its salutary effects
      diffuse beyond psychological experience and include long-term effects on physical
      functioning.

PMID- 25586075
TI  - Analysis of gallstone composition and structure in Jharkhand region.
AB  - AIM: The aim of this study was to analyze gallstones structurally and chemically
      as this may help to direct the measures for its treatment. METHODOLOGY: On the
      basis of morphology, 459 gallstones were categorized into pigmented, cholesterol,
      and mixed gallstones and analyzed for their chemical structure and composition.
      Elementary analysis was done with the help of inductively coupled plasma, optical
      emission spectrophotometry. Fourier transform infrared spectroscopy was used for
      compound analysis. The effects of thermal stability were analyzed by thermal
      gravimetric analysis (TGA). Statistical analysis was done to correlate gallstone
      composition with their shape and number in gallbladder. RESULTS: Pigmented
      gallstones were predominant and generally occurred in multiple forms, cholesterol
      as solitaire and black pigmented as slug (chi (2) = 3.56; p < 0.001). Scanning
      electron microscopy showed the crystals of cholesterol in cholesterol gallstones
      while pigmented gallstones were more compact in structure. Both types of
      structure were seen in mixed stones while black pigmented stones were amorphous
      in nature. This difference in structures might be due to difference in chemical
      compositions. Cholesterol and mixed stones contained basically cholesterol, brown
      pigmented constituted bilirubin as a major component, and black stones differed
      from brown pigmented stones by the presence of Ca palmitate. Bilirubin and
      palmitate were thermally more stable than cholesterol; hence pigmented gallstones
      were thermally more stable than cholesterol gallstones, as seen in TGA study.
      CONCLUSION: Pigmented gallstones were most common in this study of gallstones
      from the Jharkhand region.

PMID- 25586076
TI  - Double pylorus sign.

PMID- 25586077
TI  - Protection against 1,2-di-methylhydrazine-induced systemic oxidative stress and
      altered brain neurotransmitter status by probiotic Escherichia coli CFR 16
      secreting pyrroloquinoline quinone.
AB  - Exposure to environmental pollutant 1,2-dimethylhydrazine (DMH) is attributed to
      systemic oxidative stress and is known to cause neurotropic effect by altering
      brain neurotransmitter status. Probiotics are opted as natural therapeutic
      against oxidative stress and also have the ability to modulate gut-brain axis.
      Pyrroloquinoline quinone (PQQ) is water-soluble, heat-stable antioxidant
      molecule. Aim of the present study was to evaluate the antioxidant efficacy of
      PQQ-producing probiotic E. coli CFR 16 on DMH-induced systemic oxidative damage
      and altered neurotransmitter status in rat brain. Adult virgin Charles Forster
      rats (200-250 g) were given DMH dose (25 mg/kg body weight, s.c.) for 8 weeks.
      Blood lipid peroxidation levels exhibited a marked increase while antioxidant
      enzyme activities of superoxide dismutase, catalase, glucose-6-phosphate
      dehydrogenase and glutathione peroxidase were found to be reduced in DMH-treated
      rats. Likewise, brain serotonin and norepinephrine levels displayed a significant
      decrease, whereas epinephrine levels demonstrated a marked increase in brain of
      these rats. PQQ-producing E. coli CFR 16 supplementation reduced systemic
      oxidative stress and also restored brain neurotransmitter status. However, E.
      coli CFR 16 did not show any effect on these parameters. In contrast, E. coli CFR
      16:: vgb-gfp and E. coli CFR 16:: vgb-gfp vector exhibited some degree of
      protection again oxidative stress but they were not able to modulate
      neurotransmitter levels. In conclusion, continuous and sustained release of PQQ
      by probiotic E. coli in rat intestine ameliorates systemic oxidative stress and
      restored brain neurotransmitter levels.

PMID- 25586078
TI  - Biofilm formation by Staphylococcus aureus isolates from skin and soft tissue
      infections.
AB  - Many diseases caused by Staphylococcus aureus are associated with biofilm
      formation. However, the ability of S. aureus isolates from skin and soft tissue
      infections to form biofilms has not yet been investigated. We tested 160 isolates
      from patients with various skin infections for biofilm-forming capacity in
      different growth media. All the isolates formed biofilms, the extent of which
      depended on the type of growth medium. The thickest biofilms were formed when
      both plasma and glucose were present in the broth; in this case, S. aureus
      incorporated host fibrin into the biofilm's matrix. There were no differences in
      the biofilm formation between isolates from different types of skin infections,
      except for a particularly good biofilm formation by isolates from diabetic wounds
      and a weaker biofilm formation by isolates from impetigo. In conclusion, biofilm
      formation is a universal behavior of S. aureus isolates from skin infections. In
      some cases, such as in diabetic wounds, a particularly strong biofilm formation
      most likely contributes to the chronic and recurrent character of the infection.
      Additionally, as S. aureus apparently uses host fibrin as part of the biofilm
      structure, we suggest that plasma should be included more frequently in in vitro
      biofilm studies.

PMID- 25586079
TI  - Genotypic analyses and virulence characterization of Listeria monocytogenes
      isolates from crayfish (Procambarus clarkii).
AB  - Listeria monocytogenes is a foodborne pathogen that can cause invasive illness in
      humans and farm animals. It is frequently isolated from dairy products and
      poultry. However, there have been few literatures on the genetic diversity and
      virulence potential of L. monocytogenes from freshwater animal. Thirty-nine L.
      monocytogenes strains from crayfish were isolated and identified in this study.
      Molecular subtyping and polymorphism of each isolate were analyzed by multilocus
      sequence typing (MLST). MLST divided the isolates into eight sequence types
      (STs), six of which from crayfish were the same with the isolates from
      environment and clinic. PCR detection of the eight genes related to virulence and
      multiplex PCR for serotyping showed that the eight virulence factors were present
      in the isolates and all the isolates belonged to four major L. monocytogenes
      serotype groups (1/2a, 1/2b, 1/2c, and 4b) frequently isolated from patients. In
      vivo pathogenicity of isolates was also evaluated in murine model and survival
      curve of infected mice suggested that ST1, ST4, and ST9 isolates were as virulent
      as the reference strain EGDe. This study provides preliminary insights into the
      genetic diversity of L. monocytogenes from crayfish and the genetic correlation
      between crayfish and clinical L. monocytogenes isolates. The results indicate the
      contamination in aquaculture could be the source of Listeria contamination and
      the isolates are likely to cause human listeriosis.

PMID- 25586081
TI  - Idiopathic pulmonary haemosiderosis with celiac disease (Lane-Hamilton syndrome)
      in an adult - a case report.
AB  - Idiopathic pulmonary haemosiderosis (IPH) is a rare disorder of unknown cause
      characterised by haemoptysis, diffuse alveolar infiltrates and iron-deficiency
      anaemia. IPH predominantly affects children; it is rare in adults, in whom it
      usually manifests before 30 years. In adults, course is protracted with a better
      prognosis, in contrast to children. Even rarer is the Lane-Hamilton syndrome, a
      condition in which IPH is associated with celiac disease. Only 15 cases of Lane
      Hamilton syndrome affecting adults are reported in literature. Treatment of IPH
      is based on anecdotal case reports and case series because of its rare
      occurrence. High-dose steroids reportedly reduce morbidity and mortality and
      delays or stops disease progression; more effectively in adults than children. In
      Lane-Hamilton syndrome, a gluten-free diet for the celiac disease in addition to
      steroids for IPH, is the mainstay of therapy. The optimal treatment duration of
      steroid therapy is not known but anecdotally a more prolonged course results in
      improved outcome. We report a case of a young woman who presented with exertional
      dyspnoea, intermittent haemoptysis, severe anaemia and lung infiltrates but no
      gastrointestinal complaints. After extensive work-up, she was diagnosed with Lane
      Hamilton syndrome based on a diagnosis of IPH made from lung biopsy and
      concomitant celiac disease because of positive anti-gliadin antibody and
      endomyosial antibody and jejunal biopsy. She was treated with sustained low-dose
      steroid therapy for a year and a gluten-free diet with resolution of her
      symptoms, anaemia and lung infiltrates. At 4 years of follow-up, she remains
      stable, without recurrence. 

PMID- 25586080
TI  - Analysis and elucidation of phosphoenolpyruvate carboxylase in cyanobacteria.
AB  - Phosphoenolpyruvate carboxylase (PEPC) a cytosolic enzyme of higher plants is
      also found in bacteria and cyanobacteria. Genetic and biochemical investigations
      have indicated that there are several isoforms of PEPC belonging to C3; C3/C4 and
      C4 groups but, the evolution of PEPC in cyanobacteria is not yet understood. The
      present study opens up an opportunity to understand the isoforms and functions of
      PEPC in cyanobacteria. The variations observed in PEPC among lower and higher
      orders of cyanobacteria, suggests convergent evolution of PEPC. There is a
      specific PEPC phosphorylation residue 'serine' at the N-terminus and PEPC
      determinant residue 'serine' at the C-terminal that facilitates high affinity for
      substrate binding. These residues were unique to higher orders of cyanobacteria,
      but, not in lower orders and other prokaryotes. The different PEPC forms of
      cyanobacteria were investigated for their kinetic properties with
      phosphoenolpyruvate as the substrate and the findings corroborated well with the
      in silico findings. In vitro enzymatic study of cyanobacteria belonging to three
      different orders demonstrated the role of aspartate as an allosteric effector,
      which inhibited PEPC by interacting with the highly conserved residues in the
      active site. The differences in mode of inhibition among the different order,
      thus, give a fair picture about the cyanobacterial PEPCs. The higher orders
      appear to possess the sequence coordinates and functionally conserved residues
      similar to isoforms of C4 type higher plants, whereas isoforms of PEPC of the
      lower orders did not resemble either that of C3 or C4 plants. 

PMID- 25586082
TI  - Epidural Steroid Injections are Safe and Effective: Multisociety Letter in
      Support of the Safety and Effectiveness of Epidural Steroid Injections.
AB  - BACKGROUND: In April 2014, the Food and Drug Administration (FDA) issued a Drug
      Safety Communication requesting that corticosteroid labeling include warnings
      that injection of corticosteroids into the epidural space of the spine may result
      in rare but serious adverse events, including loss of vision, stroke, paralysis,
      and death. RESULTS: The International Spine Intervention Society spearheaded a
      collaboration of more than a dozen other medical societies in submitting the
      letter below to the FDA on November 7, 2014. We are publishing the letter to
      ensure that the readership of Pain Medicine is aware of the multisociety support
      for the safety and effectiveness of these procedures. A special note of thanks to
      all of the societies who signed on in support of the message.

PMID- 25586083
TI  - Anesthetic Management of Parturients With a Fontan Circulation: A Review of
      Published Case Reports.
AB  - Parturients with Fontan physiology provide unique and complex challenges to
      anesthesiologists. Such challenges include the maintenance of a perfect balance
      between preload, pulmonary vascular resistance, afterload, and cardiac output in
      a setting of a single ventricle physiology. The physiological changes of
      pregnancy add additional burden to an already "fragile" physiology, making the
      anesthetic management for labor and/or cesarean delivery even more complex.
      Understanding the impact of these changes on the Fontan physiology and the effect
      of anesthetic choices on this dyad (pregnancy-Fontan) is an imperative prior to
      caring for these patients. In an effort to determine how these patients are best
      managed for labor and/or cesarean delivery, we have reviewed the literature
      examining the peripartum anesthetic management of parturients with Fontan
      circulation and have identified 27 case reports. 

PMID- 25586084
TI  - Variability of oxygenation in possible hepatopulmonary syndrome: effects of
      requiring two abnormal arterial blood gas results for diagnosis.
AB  - BACKGROUND AND AIMS: Hepatopulmonary syndrome (HPS) affects 10-32 % of patients
      with cirrhosis and is defined by liver abnormalities, intrapulmonary vascular
      dilatations (IPVDs), and abnormal oxygenation. However, published criteria for
      abnormal oxygenation are inconsistent. We sought to evaluate variation in
      oxygenation over time and to compare various diagnostic criteria for validity,
      based on their diagnostic stability over time and ability to identify patients
      with clinically relevant findings. METHODS: We retrospectively analyzed
      oxygenation and diffusion capacity in patients with liver abnormalities and IPVDs
      who had >= 2 arterial blood gases (ABGs) at the University of Toronto or
      Universite de Montreal. We compared the performance of nine possible oxygenation
      criteria for HPS and for each explored whether validity improved when requiring
      two consecutive abnormal ABGs on different days. RESULTS: Mean PaO2 was 68.4 mmHg
      and annual within-patient coefficient of variation 6.3 % (58 patients). Applying
      published criteria, 8.6-15.5 % of patients initially diagnosed with HPS no longer
      met the criterion for HPS on a subsequent ABG (re-classified). Requiring two
      consecutive abnormal ABGs on different days: (1) reduced the proportion of re
      classified patients (9/9 criteria); (2) identified patients with more rapid
      progression in hypoxemia and greater difference in rate of progression between
      HPS and non-HPS (7/9 criteria); and (3) identified patients with lower diffusion
      and a larger difference in diffusion between HPS and non-HPS (8/9 criteria).
      CONCLUSIONS: Oxygenation is variable in this population, and requiring two
      abnormal results might reduce misdiagnosis and better differentiate patients with
      and without HPS according to clinically relevant markers of disease.

PMID- 25586085
TI  - A case series and literature review of Merkel cell carcinoma metastasizing to
      pancreas.
AB  - BACKGROUND: Merkel cell carcinoma is a rare aggressive tumor arising from the
      mechanoreceptors of the epidermis with a relative higher mortality rate stage for
      stage than melanoma. Microscopically, the cells appear similar to small cell lung
      cancer, but they specifically stain positive for CK20 and are negative for TTF-1.
      It is rarely known to metastasize to the pancreas. AIMS: To report four cases of
      Merkel cell carcinoma metastasizing to pancreas and compare them to previously
      reported patients. METHODS: We performed a retrospective review of all patients
      who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a
      suspected pancreatic lesion between January 2004 and December 2012. We reviewed
      other reported cases with a literature search using PubMed, Embase, and Scopus.
      RESULTS: Four male patients with mean age of 66 years were found to have
      metastatic disease in the pancreas on average 29 months after initial diagnosis
      of MCC. Two cases were diagnosed with EUS-FNA and two with PET-CT. Three patients
      had multifocal pancreatic involvement which has not been previously described.
      All four patients died within 3-9 months following tumor spread to the pancreas.
      Merkel cell carcinoma rarely metastasizes to the pancreas with only 10 cases
      being described in the medical literature. CONCLUSIONS: EUS-FNA is an effective
      tool that can be utilized in diagnosing pancreatic masses. Differentiating
      metastatic pancreatic tumors, especially Merkel cell carcinoma from primary
      pancreatic tumor is useful as systemic therapy is an option in pancreatic
      adenocarcinoma, but is ineffective in metastatic Merkel cell carcinoma.

PMID- 25586086
TI  - Oxidative stress might play a role in low serum vitamin D associated liver
      fibrosis among patients with autoimmune hepatitis.

PMID- 25586087
TI  - Fecal calprotectin evaluation in patients with ulcerative colitis.

PMID- 25586088
TI  - Long-Term Outcomes of Endoscopic Versus Surgical Resection of Superficial
      Submucosal Colorectal Cancer.
AB  - BACKGROUND: The long-term outcomes of endoscopic resection of superficial
      submucosal colorectal cancer (CRC) had not been adequately compared with those of
      surgical resection. AIMS: We aimed to compare the long-term clinical outcomes of
      endoscopic resection of superficial submucosal CRC to those of surgical
      resection. METHODS: Submucosal CRC patients with a tumor depth of sm1 or less
      than 1 mm from the muscularis mucosa were enrolled. Patients with unfavorable
      histology, such as poorly differentiated cancer or lymphovascular invasion, were
      excluded. Recurrence-free survival and overall survival were investigated in 87
      patients who underwent endoscopic resection and in 171 patients who underwent
      surgical resection. RESULTS: The mean ages of the endoscopic and surgical
      resection groups were 59.7 and 59.8 years, respectively. Hospital stay was
      shorter in the endoscopic resection group (1.7 +/- 1.6 vs. 8.6 +/- 3.8 days; p <
      0.001). The 3- and 5-year recurrence-free survival rates were 98.7 and 96.7 % in
      the endoscopic resection group and 98.7 and 97.5 % in the surgical resection
      group, respectively (p = 0.837). The 3- and 5-year overall survival rates were
      100.0 and 95.2 % in the endoscopic resection group and 98.7 and 92.8 % in the
      surgical resection group, respectively (p = 0.928). Recurred cases showed an
      unfavorable histology that was overlooked at the time of initial resection.
      CONCLUSIONS: Long-term outcomes after endoscopic resection of superficial
      submucosal CRC are comparable to those after surgical resection. Thorough initial
      histopathological evaluations are needed to guarantee the correct indication for
      endoscopic resection of submucosal CRC.

PMID- 25586089
TI  - Accuracy of ultrasound and noninvasive markers of fibrosis to identify patients
      with cirrhosis.
AB  - BACKGROUND: Accurate identification of patients with cirrhosis using noninvasive
      markers of fibrosis is useful for esophageal varices and hepatocellular carcinoma
      surveillance programs. The aims of our study were to characterize the accuracy of
      ultrasonography, AST-to-platelet ratio index (APRI), and FIB-4 as noninvasive
      markers to identify the presence of cirrhosis. METHODS: We conducted a
      retrospective cohort study of patients who underwent liver biopsy at a large
      urban safety-net institution between November 2008 and July 2011. The
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value, and overall accuracy using receiver operator characteristic curve analysis
      for the detection of cirrhosis were calculated for each noninvasive marker.
      RESULTS: Liver biopsy was performed in 388 patients, of whom 93 (24.0 %) had
      cirrhosis. C-statistics for APRI and FIB-4 predicting the presence of cirrhosis
      were 0.68 (95 % CI 0.63-0.74) and 0.73 (95 % CI 0.68-0.78), respectively. The c
      statistic for a nodular appearance on ultrasound was 0.78 (95 % CI 0.72-0.83).
      The PPV of a shrunken nodular-appearing liver was 64.8 %; however, PPV was
      significantly higher in the subset with a cirrhotic-appearing liver and signs of
      portal hypertension (PPV 83.6 %, p = 0.01) as well as in the subset with a
      noninvasive fibrosis marker also suggesting cirrhosis (PPV 77.8 %, p < 0.001).
      CONCLUSION: Serum and imaging noninvasive markers of fibrosis may have
      insufficient accuracy when used in isolation; however, a combination of markers
      may allow sufficient accuracy to systematically identify patients with cirrhosis.

PMID- 25586090
TI  - Colon PillCam: why not just take a pill?
AB  - This review article deals with the clinical value of capsule endoscopy for
      visualization of the colon. Since its introduction in 2006, the colon capsule
      endoscopy underwent major technological improvements. The improved performance of
      colon capsule endoscopy is reviewed based on three multicenter prospective
      studies. Screening patients for colonic adenomatous polyps is reasonable in
      patients who are unwilling to undergo conventional colonoscopy. Another
      prospective study proved that colon capsule endoscopy is effective in incomplete
      colonoscopy. Colon capsule endoscopy was shown to be superior to virtual
      colonography in the evaluation of patients with incomplete colonoscopy. Further
      improvements are expected in colon capsule endoscopy. 

PMID- 25586091
TI  - Hepatitis C direct antiviral drugs and hepatic decompensation in patients with
      advanced cirrhosis: culprit or innocent bystander?

PMID- 25586093
TI  - Residual rectal mucosa after stapled vs. handsewn ileal J-pouch-anal anastomosis
      in patients with familial adenomatous polyposis coli (FAP)--a critical issue.
AB  - INTRODUCTION: Restorative proctocolectomy has become the standard surgical
      procedure for familial adenomatous polyposis (FAP) patients. The use of stapler
      devices has initiated a controversial discussion concerning the ileal pouch-anal
      reconstruction. Some authors advocate a handsewn anastomosis after transanal
      mucosectomy. A double-stapled anastomosis leads to better functional results but
      seems to bear a higher risk of residual rectal mucosa with dysplasia and
      adenomas. The present study systematically analyses the rate of residual rectal
      mucosa after restorative proctocolectomy and handsewn vs. stapled anastomosis.
      PATIENTS AND METHODS: One hundred FAP patients after restorative proctocolectomy
      undergoing regular follow-up at our outpatient clinic were included in the study.
      Proctoscopy with standardised biopsy sampling was performed. RESULTS: Of the 100
      patients, 50 had undergone a stapled and 50 a handsewn anastomosis. Median follow
      up was 146.1 months (handsewn) vs. 44.8 months (stapled) (P < 0.0001). Eighty
      seven patients received a proctoscopy with standardised biopsy sampling. Thirteen
      patients had been diagnosed with residual rectal mucosa before. Sixty-three
      patients (63 %) showed remaining rectal mucosa (42 (66.6 %) stapler, 21 (33.3 %)
      handsewn, P < 0.0001). Patients after stapled anastomosis had higher rates of
      circular rectal mucosa seams, while small mucosa islets predominated in the
      handsewn group. The rate of rectal adenomas was significantly higher in the
      stapler group (21 vs. 10, P = 0.02). CONCLUSION: Rectal mucosa, especially wide
      mucosa seams, as well as rectal adenomas are found significantly more often after
      a stapled than after a handsewn anastomosis. As the follow-up interval in the
      stapler group was significantly shorter, the impact of these findings may still
      be underestimated.

PMID- 25586092
TI  - The genetic basis for cognitive ability, memory, and depression symptomatology in
      middle-aged and elderly chinese twins.
AB  - The genetic influences on aging-related phenotypes, including cognition and
      depression, have been well confirmed in the Western populations. We performed the
      first twin-based analysis on cognitive performance, memory and depression status
      in middle-aged and elderly Chinese twins, representing the world's largest and
      most rapidly aging population. The sample consisted of 384 twin pairs with a
      median age of 50 years. Cognitive function was measured using the Montreal
      Cognitive Assessment (MoCA) scale; memory was assessed using the revised Wechsler
      Adult Intelligence scale; depression symptomatology was evaluated by the self
      reported 30-item Geriatric Depression (GDS-30)scale. Both univariate and
      multivariate twin models were fitted to the three phenotypes with full and nested
      models and compared to select the best fitting models. Univariate analysis showed
      moderate-to-high genetic influences with heritability 0.44 for cognition and 0.56
      for memory. Multivariate analysis by the reduced Cholesky model estimated
      significant genetic (rG = 0.69) and unique environmental (rE = 0.25) correlation
      between cognitive ability and memory. The model also estimated weak but
      significant inverse genetic correlation for depression with cognition (-0.31) and
      memory (-0.28). No significant unique environmental correlation was found for
      depression with other two phenotypes. In conclusion, there can be a common
      genetic architecture for cognitive ability and memory that weakly correlates with
      depression symptomatology, but in the opposite direction. 

PMID- 25586094
TI  - High admission C-reactive protein level and longer in-hospital delay to surgery
      are associated with increased risk of complicated appendicitis.
AB  - PURPOSE: Debate on the effect of in-hospital delay on the risk of perforation in
      appendicitis persists, and the results from previous studies are controversial.
      The aims of this study were to present the effect of in-hospital delay on the
      risk of perforation in appendicitis and to assess the utility of C-reactive
      protein (CRP) measurement in detecting the patients with complicated
      appendicitis. METHODS: Prospectively collected data of 389 adult patients who
      underwent surgery for acute appendicitis were analyzed in order to find the most
      accurate method for recognizing the pre-hospital perforations. The effect of in
      hospital delay on the further risk of perforation in patients with not yet
      perforated acute appendicitis was then analyzed. RESULTS: Out of 389 patients
      with appendicitis, 91 patients (23.4 %) had complicated appendicitis, 23 with
      abscess, and 68 with free perforation. Admission CRP level of 99 mg/l or higher
      was 90.3 % specific for complicated appendicitis. In patients with admission CRP
      less than 99 mg/l, the incidence of perforation doubled from 9.5 to 18.9 % when
      the in-hospital delay increased from less than 6 h to more than 12 h.
      CONCLUSIONS: Complicated appendicitis can be identified with a high CRP level on
      admission. Delaying surgery can increase the risk of perforation.

PMID- 25586095
TI  - Increases urinary HMGA1 in serous epithelial ovarian cancer patients.
AB  - BACKGROUND: Serous epithelial ovarian cancer is the most common variety of
      ovarian cancer and is currently diagnosed using serum CA-125 levels. HMGA1 a
      small 10.6-12 kDa protein, has been implicated as a potentially important tumor
      biomarker and may enter the urinary trace, thus potentially able to serve as a
      disease biomarker. OBJECTIVE: To determine if urine HMGA1 can be detected and
      potentially serve as a clinical diagnostic biomarkers. METHOD: Urine was
      collected from 20 healthy normal control patients, 20 patients with benign
      gynecological disease and 55 epithelial ovarian specimens of which 20 exhibited
      G1/2 ovarian cancer and 35 G3 ovarian cancers. Serum was also collected from 20
      healthy normal control patients and 55 serous epithelial ovarian cancers
      patients. HMGA1 levels were examined via enzyme-linked immunosorbent assay
      (ELISA) and were reported independently and normalized to urine creatinine
      levels. Serum CA-125 levels were examined via enzyme assay and the data was
      analyzed via box and ROC analysis. RESULTS: Urine HMGA1 was significantly
      elevated in serous epithelial ovarian cancer specimen relative to healthy control
      specimens with G3 specimens exhibiting higher levels than G1-G2 specimens. ROC
      analysis revealed a high degree of sensitivity and specificity for urine HMGA1
      detection in ovarian cancer, with a higher AUC value noted for urine HMGA1 than
      serum CA-125. Furthermore, urine HMGA1 and serum CA-125 combined AUC indicated
      that urine HMGA1 is an excellent diagnostic biomarker for serous epithelial
      ovarian cancer. CONCLUSION: Our data indicates that measuring urine HMGA1 may
      serve as a useful diagnostic tool.

PMID- 25586096
TI  - Benign prostatic hyperplasia and prostate cancer differentiation via platelet to
      lymphocyte ratio.
AB  - BACKGROUND: The aim of the current study is to evaluate NLR and PLR inflammation
      markers in PCa and BPH. METHODS: Clinical and pathological data such as age,
      prostate volume, PSA, NLR, and PLR levels of 201 patients were retrospectively
      reviewed. Pathological sample results of these patients were categorized either
      as benign or malign. The benign group consisted of chronic prostatitis and BPH
      and the malign group of PCa. The PSA levels were divided into three categories as
      PSA: 0-4 ng/ml, PSA: 4-10 ng/ml, and 10 ng/ml and above. RESULTS: In the benign
      category, the mean PLR values for PSA: 0-4 ng/ml is 131.8 +/- 31.2, for PSA: 4-10
      ng/ml 124.7 +/- 83.9 and 10 ng/ml and above 124 +/- 53 in chronic prostatitis
      group and in the BPH group for PSA: 4-10 ng/ml 120.3 +/- 45.1, for PSA: 4-10
      ng/ml 126 +/- 54.2, and 10 ng/ml and above 191.4 +/- 176.1. In the malign
      category, the mean PLR values of PCa patients is for PSA: 0-4 ng/ml 122.8 +/-
      43.8, for PSA: 4-10 ng/ml 123 +/- 43.8, and above 10 ng/ml 179.1 +/- 94. Related
      to the variables of age, NLR, and mean prostate volume, there were no
      statistically significant differences. Statistically significant differences were
      observed in the mean PLR values only if the PSA level was 10 ng/ml and above (p:
      0.044) in the BPH and PCa groups. The correlation of the PCa Gleason score and
      PSA, NLR and PLR parameters in the malign category revealed no statistically
      significant differences (P > 0.05). CONCLUSION: Effective malign and benign
      differentiation of prostate pathologies based on noninvasive inflammation
      biomarkers such NLR and PLR necessitate clinical studies with larger patient
      series.

PMID- 25586097
TI  - Heparanase is involved in proliferation and invasion of ovarian cancer cells.
AB  - Heparanase(HPSE), an endo-beta -D-glucuronidase, is found overexpressed in
      Ovarian cancer (OC). The purpose of our work was to investigate primitively the
      possible role of HPSE in the development of OC. In this study, RNA interference
      (RNAi) with a HPSE small hairpin RNAs(HPSE-shRNA) and plasmid with HPSE were used
      to identify the effects of HPSE on the regulation of malignant behaviors of OC.
      OV-90 and SKOV3 were selected as a cell model in vitro and in vivo. The results
      showed that down-regulation of HPSE can significantly inhibit the proliferative
      and invasive ability of SKOV3 cells, and up-regulation of HPSE in OV-90 cells
      showed the opposite effects. Compared with the parental OC cells, HPSE silencing
      cells exhibited attenuated capacities in developing tumor in nude mice, while the
      growth tumors xenografts derived from these cells were dramatically regressed. In
      conclusion, our results suggest that HPSE contributes to the proliferation and
      metastasis of OC and HPSE might be a potent molecular target for OC treatment. 

PMID- 25586098
TI  - Golgi/plastid-type manganese superoxide dismutase involved in heat-stress
      tolerance during grain filling of rice.
AB  - Superoxide dismutase (SOD) is widely assumed to play a role in the detoxification
      of reactive oxygen species caused by environmental stresses. We found a
      characteristic expression of manganese SOD 1 (MSD1) in a heat-stress-tolerant
      cultivar of rice (Oryza sativa). The deduced amino acid sequence contains a
      signal sequence and an N-glycosylation site. Confocal imaging analysis of rice
      and onion cells transiently expressing MSD1-YFP showed MSD1-YFP in the Golgi
      apparatus and plastids, indicating that MSD1 is a unique Golgi/plastid-type SOD.
      To evaluate the involvement of MSD1 in heat-stress tolerance, we generated
      transgenic rice plants with either constitutive high expression or suppression of
      MSD1. The grain quality of rice with constitutive high expression of MSD1 grown
      at 33/28  degrees C, 12/12 h, was significantly better than that of the wild
      type. In contrast, MSD1-knock-down rice was markedly susceptible to heat stress.
      Quantitative shotgun proteomic analysis indicated that the overexpression of MSD1
      up-regulated reactive oxygen scavenging, chaperone and quality control systems in
      rice grains under heat stress. We propose that the Golgi/plastid MSD1 plays an
      important role in adaptation to heat stress.

PMID- 25586100
TI  - Poorer mental health in UK bisexual women than lesbians: evidence from the UK
      2007 Stonewall Women's Health Survey.
AB  - BACKGROUND: Bisexual- and lesbian-identified women have significantly worse
      mental health than heterosexual women. Less evidence exists about mental health
      differences between lesbian and bisexual women. METHODS: Self-completion survey
      with community-based, opportunistic sampling recruited 937 bisexual-identified
      and 4769 lesbian-identified women. Associations between sexual identity and
      mental health indicators were assessed by logistic regression, controlling for
      age, income, student status and employment. RESULTS: As a group, bisexual women
      were younger, poorer, and more likely to be trans-identified, minority ethnic
      identified and to use marijuana, compared with lesbians. Bisexuals were more
      likely than lesbians to report eating problems (adjusted odds ratio (AOR) = 1.64,
      P < 0.001), self-harm (AOR = 1.37, P = 0.001), depressed feelings (AOR = 1.26, P
      = 0.022) and anxiety (AOR = 1.20, P = 0.037). Fewer bisexual women attended
      lesbian or bisexual social events, were 'out', or had experienced any sexuality
      related discrimination, compared with lesbians. CONCLUSION: More bisexual women
      reported poor mental health or psychological distress than did lesbians. Bisexual
      women may be more likely to experience social stress due to the 'double
      discrimination' of homophobia and biphobia. This stress, experienced mainly as
      internalized and felt stigma, could result in greater risk for poor mental health
      compared with lesbians. Addressing both biphobia and homophobia within UK society
      has important preventative mental health implications.

PMID- 25586101
TI  - The messenger's great message for vaccination.
AB  - Poly ribonucleic acid (RNA) is the only polymer capable to recapitulate all
      processes of life: containment of genetic information, enzymatic activities and
      capacity to create defined 3D structures. Since it has a remarkable chemical
      stability (at neutral or acidic pH) and can be modified to enhance/reduce
      particular features (e.g., stability in biological RNase containing milieus or
      recognition by immune sensors), it is a particularly versatile and ideal active
      pharmaceutical ingredient. However, the utilization of RNA as a gene vehicle
      (messenger RNA, mRNA) for therapy has only recently been exploited. Within this
      scope, mRNA-based vaccines designed to trigger anti-cancer, anti-virus or anti
      allergy immune responses have been developed. Modifications of mRNA vectors and
      implementation of adequate formulations have allowed to turn this natural
      superlative biological molecule into a safe active pharmaceutical ingredient that
      can virtually address any medical need including vaccination or immunotherapy.
      This is the newest great message delivered by this messenger. 

PMID- 25586099
TI  - Nutritional ecology beyond the individual: a conceptual framework for integrating
      nutrition and social interactions.
AB  - Over recent years, modelling approaches from nutritional ecology (known as
      Nutritional Geometry) have been increasingly used to describe how animals and
      some other organisms select foods and eat them in appropriate amounts in order to
      maintain a balanced nutritional state maximising fitness. These nutritional
      strategies profoundly affect the physiology, behaviour and performance of
      individuals, which in turn impact their social interactions within groups and
      societies. Here, we present a conceptual framework to study the role of nutrition
      as a major ecological factor influencing the development and maintenance of
      social life. We first illustrate some of the mechanisms by which nutritional
      differences among individuals mediate social interactions in a broad range of
      species and ecological contexts. We then explain how studying individual- and
      collective-level nutrition in a common conceptual framework derived from
      Nutritional Geometry can bring new fundamental insights into the mechanisms and
      evolution of social interactions, using a combination of simulation models and
      manipulative experiments. 

PMID- 25586102
TI  - Compliance does not mean quality: an in-depth analysis of the safe surgery
      checklist at a tertiary care health facility.

PMID- 25586103
TI  - Receptor for advanced glycation endproduct modulators: a new therapeutic target
      in Alzheimer's disease.
AB  - INTRODUCTION: Reduction in the deposition of amyloid beta (Abeta) has been the
      primary target for Alzheimer's disease (AD) therapeutics recently, but in
      clinical trials this approach has generally been unsuccessful. A common feature
      of AD pathology is a complex inflammatory component that could be a target for
      treatment. One feature of this inflammation has been the involvement of the
      receptor for advanced glycation endproducts (RAGE), whose ligands include
      advanced glycation-endproduct-modified proteins as well as lipids and Abeta,
      which are found at elevated levels in AD brains. AREAS COVERED: In this article,
      the authors describe the key features of RAGE and how it could have a role in AD
      pathogenesis. They also summarize experimental animal and clinical data that
      demonstrate the therapeutic effect of RAGE inhibition and consider what these
      findings mean for human disease. EXPERT OPINION: RAGE has multiple ligands,
      including Abeta, that are increased in AD brains. Inhibiting RAGE-ligand
      interactions without activating receptor signaling can reduce multiple
      pathological pathways relevant for AD. Several RAGE inhibitors and modulators are
      now being tested as therapeutics for AD. Recent Phase II studies have established
      the good safety and tolerability of TTP448 with some evidence of positive benefit
      at lower dose. This suggests that further studies are required.

PMID- 25586106
TI  - Metabolic modulation of cancer: a new frontier with great translational
      potential.
AB  - Metabolic oncology is an exciting new field in cancer research, offering a new
      window to cancer's molecular plasticity and promise for the development of
      effective, cancer-selective therapies and novel biomarkers. It is based on the
      realization that cancer's unique metabolism (known since Warburg's report in
      1923) with suppression of mitochondrial glucose oxidation and upregulation of
      cytoplasmic glycolysis is not a secondary but a primary event, offering many
      growth advantages to cancer cells. Many mechanisms have been revealed, including
      growth factors, oncogenes, and mutations, all contributing to a suppression of
      mitochondria, similar to what takes place in hypoxia. This suppression leads to
      inhibition of mitochondria-driven apoptosis, promotes proliferation, and enhances
      angiogenesis and metastatic potential. A number of molecular tools and small
      molecules targeting metabolic enzymes, including pyruvate kinase, pyruvate
      dehydrogenase kinase, isocitrate dehydrogenase, and lactate dehydrogenase, have
      been developed, inhibiting cancer growth in vitro and in vivo in several cancer
      types. Several have already entered early-phase trials, a great translational
      success considering the young age of the field (less than 10 years). Here we
      review the mechanisms and effects of these metabolic modulators and the rationale
      for further development. This rapidly accumulating knowledge allows some optimism
      that this may prove to be a paradigm shift in the way we understand and treat
      cancer. 

PMID- 25586104
TI  - Nutritional supplements in age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the most frequent cause of blindness in
      the Western World. While with new therapies that are directed towards vascular
      endothelial growth factor (VEGF), a potentially efficient treatment option for
      the wet form of the disease has been introduced, a therapeutic regimen for dry
      AMD is still lacking. There is evidence from several studies that oral intake of
      supplements is beneficial in preventing progression of the disease. Several
      formulations of micronutrients are currently available. The present review
      focuses on the role of supplements in the treatment and prevention of AMD and
      sums up the current knowledge about the most frequently used micronutrients. In
      addition, regulatory issues are discussed, and future directions for the role of
      supplementation in AMD are highlighted. 

PMID- 25586107
TI  - Nursing students' attitudes towards information and communication technology: an
      exploratory and confirmatory factor analytic approach.
AB  - AIM: The aim of this study was to develop and psychometrically test a shortened
      version of the Information Technology Attitude Scales for Health, in the
      investigation of nursing students with clinical placement experiences.
      BACKGROUND: Nurses and nursing students need to develop high levels of competency
      in information and communication technology. However, they encounter
      statistically significant barriers in the use of the technology. Although some
      instruments have been developed to measure factors that influence nurses'
      attitudes towards technology, the validity is questionable and few studies have
      been developed to test the attitudes of nursing students, in particular. DESIGN:
      A cross-sectional survey design was performed. METHODS: The Information
      Technology Attitude Scales for Health was used to collect data from October 2012
      December 2012. A panel of experts reviewed the content of the instrument and a
      pilot study was conducted. Following this, a total of 508 nursing students, who
      were engaged in clinical placements, were recruited from six universities in
      South Korea. Exploratory and confirmatory factor analyses were performed and
      reliability and construct validity were assessed. RESULTS: The resulting
      instrument consisted of 19 items across four factors. Reliability of the four
      factors was acceptable and the validity was supported. CONCLUSIONS: The
      instrument was shown to be both valid and reliable for measuring nursing
      students' attitudes towards technology, thus aiding in the current understandings
      of this aspect. Through these measurements and understandings, nursing educators
      and students are able to be more reflexive of their attitudes and can thus seek
      to develop them positively.

PMID- 25586105
TI  - PPE57 induces activation of macrophages and drives Th1-type immune responses
      through TLR2.
AB  - Proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) are related
      proteins exclusive to Mycobacteria that play diverse roles in modulating critical
      innate immune pathways. In this study, we observed that the PPE57 protein is
      associated with the cell wall and is exposed on the cell surface. PPE57 enhances
      Mycobacterium spp. entering into macrophages and plays a role in macrophage
      phagocytosis. To explore the underlying mechanism, we demonstrated that PPE57 is
      able to recognise Toll-like receptor 2 (TLR2) and further induce macrophage
      activation by augmenting the expression of several cell surface molecules (CD40,
      CD80, CD86 and MHC class II) and pro-inflammatory cytokines (TNF-alpha, IL-6 and
      IL-12p40) within macrophages. These molecules are involved in the mitogen
      activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB) signalling
      pathways. We demonstrated that PPE57 effectively polarises T cells to secrete
      interferon (IFN)-gamma and IL-2 and to up-regulate CXCR3 expression in vivo and
      in vitro, suggesting that this protein may contribute to Th1 polarisation during
      the immune response. Moreover, recombinant Bacillus Calmette-Guerin (BCG) over
      expressing PPE57 could provide better protective efficacy against Mycobacterium
      tuberculosis challenge compared with BCG. Taken together, our data provides
      several pieces of evidence that PPE57 may regulate innate and adaptive immunity
      by interacting with TLR2. These findings indicate that PPE57 protein is a
      potential antigen for the rational design of an efficient vaccine against M.
      tuberculosis. KEY MESSAGES: PPE57 is located on the cell surface and enhances
      mycobacterium entry into macrophage. PPE57 interacts directly with TLR2 on
      macrophages. PPE57 plays a key role in the activation of macrophages in a TLR2
      dependent manner. PPE57 induces a Th1 immune response via TLR2-mediated
      macrophage functions. Recombinant BCG over-expressing PPE57 could improve
      protective efficacy against M. tuberculosis.

PMID- 25586108
TI  - Investigating the roles of ascorbate-glutathione cycle and thiol metabolism in
      arsenate tolerance in ridged Luffa seedlings.
AB  - The present study is aimed to investigate whether ascorbate-glutathione cycle
      (AsA-GSH cycle) or thiol metabolism is involved in the regulation of arsenate
      (As(V))-induced oxidative stress and tolerance in ridged Luffa seedlings. As(V)
      significantly (p < 0.05) declined the growth of Luffa seedlings which was
      accompanied by the enhanced accumulation of As. The enhanced accumulation of As
      in tissues declined total protein and nitrogen contents and photosynthesis, and
      increased the accumulation of reactive oxygen species (ROS). The enhanced levels
      of ROS cause damage to lipids and proteins as indicated by the increased contents
      of malondialdehyde (MDA) and reactive carbonyl groups (RCG). The components of
      AsA-GSH cycle such as ascorbate peroxidase, monodehydroascorbate reductase,
      dehydroascorbate reductase, and reduced ascorbate were downregulated, while
      glutathione reductase and glutathione were upregulated by As(V) stress. Thiol
      metabolic enzymes such as cysteine synthase, gamma-glutamylcysteine synthetase,
      and glutathione synthetase, and compounds such as cysteine, glutathione, and non
      protein thiols were stimulated by As(V) stress. These results suggest that thiol
      metabolism plays a key role in mitigating As(V)-mediated further damage to Luffa
      seedlings, while AsA-GSH cycle components had a little role in imparting As(V)
      tolerance. The present study provides information regarding the involvement of
      AsA-GSH cycle and thiol metabolism in imparting As(V) tolerance in Luffa. The
      results of this study can be utilized for As(V) toxicity management in Luffa
      while keeping these biochemical components into consideration.

PMID- 25586109
TI  - Wheat cultivars differing in heat tolerance show a differential response to
      oxidative stress during monocarpic senescence under high temperature stress.
AB  - Wheat crop may experience heat stress during post-anthesis phase associated with
      oxidative stress, enhanced senescence, and reduced productivity. Stay green is a
      desirable character for the selection for heat tolerance in wheat. In the present
      study, antioxidant metabolism was studied under post-anthesis heat stress in
      field during monocarpic senescence by comparing two wheat genotypes, namely
      Hindi62 (heat tolerant and delayed senescent) and PBW343 (heat susceptible and
      early senescent). Hindi62 exhibited lesser oxidative stress, membrane damage, and
      coordinated antioxidant defense as compared to PBW343 under heat stress during
      post-anthesis stage. Higher activity of SOD, CAT, APX, GR, and MDHAR under heat
      stress contributed towards delayed senescence in Hindi62 compared to PBW343.
      GSH/GSSG ratio was also maintained at higher level in Hindi62 under heat stress
      compared to PBW343 during senescence. Hence, the present study clearly shows that
      upregulated level of the total antioxidant capacity during grain development
      contributed towards delayed senescence and heat tolerance in Hindi62 compared to
      the heat-susceptible PBW343. 

PMID- 25586111
TI  - Validation of Turkish health literacy measures.
AB  - This study aimed to validate a Turkish version of the Short Test of Functional
      Health Literacy (S-TOFHLA) (Baker et al, Development of a brief test to measure
      functional health literacy. Patient Educ Counsel 1999; 38: :33-42) and a Turkish
      version of the Chew self-report scale (Chew et al., Brief questions to identify
      patients with inadequate health literacy. Family Med, 2004; 36: :588-94) for
      measuring functional health literacy. The original English version of the S
      TOFHLA and the Chew items were translated by applying standardized translation
      methods and cultural adaptations, and both were administered to a sample of
      diabetes patients (N = 302) in two diabetes clinics in one of the major cities in
      Turkey. Self-administered paper-pencil questionnaires were distributed to
      eligible outpatients who had a clinic appointment. In addition to the S-TOFHLA
      measurement and the Chew screening questions, gender, age, educational
      attainment, income, marital status and diabetes knowledge were obtained. The
      Turkish version of S-TOFHLA showed high internal consistency. Both S-TOFHLA and
      the Chew screening scale correlated significantly with known predictors of health
      literacy: age, education and income. The Chew scale was also related weakly but
      significantly with general diabetes knowledge. It is expected that the Turkish
      versions of S-TOFHLA and the Chew scale will be used in Turkey as well as in
      other countries with large Turkish communities. 

PMID- 25586110
TI  - Expression analysis of biosynthetic pathway genes vis-a-vis podophyllotoxin
      content in Podophyllum hexandrum Royle.
AB  - Podophyllum hexandrum Royle is known for its vast medicinal properties,
      particularly anticancer. It contains higher amount of podophyllotoxin (4.3 %),
      compared to Podophyllum peltatum (0.025 %) and other plant species; as a result,
      it has been used worldwide in the preparation of various drugs including
      anticancer, antimalarial, antiviral, antioxidant, antifungal, and so on.
      Currently, Etoposide (VP-16-213), Vumon(r) (Teniposide; VM-26), Etopophos(r), Pod
      Ben- 25, Condofil, Verrusol, and Warticon are available in the market. Due to
      highly complex synthesis and low cell culture yields of podophyllotoxin (0.3 %),
      the supply of raw material cannot be met due to increasing industrial demands.
      The knowledge on podophyllotoxin biosynthetic pathway vis-a-vis expression status
      of genes is fragmentary. Quantitative expression analysis of 21 pathway genes has
      revealed 9 genes, namely SD, PD, PCH, CM, CMT, CAD, CCR, C4H, and ADH, that
      showed increase in transcript abundance up to 1.4 to 23.05 folds, respectively,
      vis-a-vis podophyllotoxin content in roots (1.37 %) and rhizomes (3.05 %) of P.
      hexandrum. In silico analysis of putative cis-regulatory elements in promoter
      regions of overexpressed genes showed the presence of common Skn-1 motif and MBS
      elements in CMT, CAD, CCR, C4H, and ADH genes, thereby, suggesting their common
      regulation. The outcome of the study has resulted in the identification of
      suitable candidate genes which might be contributing to podophyllotoxin
      biosynthesis that can act as potential targets for any genetic intervention
      strategies aimed at its enhanced production.

PMID- 25586112
TI  - Perceived health-related self-efficacy associated with BMI in adults in a
      population-based survey.
AB  - BACKGROUND: The concept of ability to control personal behaviour in various
      environmental temptations is called self-efficacy. The high prevalence of obesity
      and overweight in Finland is the reason for studying the determinants of weight.
      The aim of the present study was to clarify the associations between body mass
      index and health-related self-efficacy (HSE), including food patterns, health
      behaviour and education. METHODS: A random sample of adults was invited to the
      cross-sectional FINRISK 2002 Study in six regions in Finland. Participants
      (n=7784) gave information on education, health behaviour, HSE and food
      consumption. Height and weight were measured in a health examination. The
      response rate was 60% for men and 71% for women. Six food patterns were
      identified by principal component analysis on the basis of food consumption. The
      scores from seven-item HSE was calculated and categorized into tertiles for the
      analysis. The associations of BMI with self-efficacy and exploratory variables
      were tested using general linear modelling in total population and by gender.
      RESULTS: A weak HSE was associated with a higher BMI after adjusting for age,
      education, food patterns and health behaviour. In addition, low education,
      infrequent PA and non-smoking were associated with the higher BMI, but the
      association of HSE and BMI remained in multivariate model. The associations of
      food patterns and BMI were small. The adverse association with BMI was observed
      for patterns with sweet and butter. CONCLUSION: The study supports the importance
      of self-control in weight management, which needs to be considered as an
      empowerment tool in health education.

PMID- 25586113
TI  - Counterfactual comparison modulates fairness consideration in the mini-ultimatum
      game: an event-related potentials study.
AB  - Existing literature on the mini-ultimatum game indicates that counterfactual
      comparison between chosen and unchosen alternatives is of great importance for
      individual's fairness consideration. However, it is still unclear how
      counterfactual comparison influences the electrophysiological responses to unfair
      chosen offers. In conjunction with event-related potentials' (ERPs) technique,
      the current study aimed to explore the issue by employing a modified version of
      the mini-ultimatum game where a fixed set of two alternatives (unfair offer vs.
      fair alternative, unfair vs. hyperfair alternative, unfair offer vs. hyperunfair
      alternative) was presented before the chosen offer. The behavioral results showed
      that participants were more likely to accept unfair chosen offers when the
      unchosen alternative was hyperunfair than when the unchosen alternative was fair
      or hyperfair. The ERPs results showed that the feedback-related negativity (FRN)
      elicited by unfair chosen offers was insensitive to the type of unchosen
      alternative when correcting for possible overlap with other components. In
      contrast, unfair chosen offers elicited larger P300 amplitudes when the unchosen
      alternative was hyperunfair than when the unchosen alternative was fair or
      hyperfair. These findings suggest that counterfactual comparison may take effect
      at later stages of fairness consideration as reflected by the P300. 

PMID- 25586115
TI  - Left Bundle Branch Block in Cardiovascular Disease: Clinical Significance and
      Remaining Controversies.

PMID- 25586114
TI  - Influence of droplet size on the antioxidant activity of rosemary extract loaded
      oil-in-water emulsions in mixed systems.
AB  - The influence of droplet size on the antioxidant activity of oil-in-water
      emulsions loaded with rosemary extract in mixed emulsion systems was
      investigated. Firstly, differently sized hexadecane-in-water model emulsions (10%
      (w/w) hexadecane, 2% (w/w) Tween 80, pH 5 or 7) containing 4000 ppm rosemary
      extract in the oil phase or without added antioxidant were prepared using a high
      shear blender and/or high-pressure homogenizer. Secondly, emulsions were mixed
      with fish oil-in-water emulsions (10% (w/w) fish oil, 2% (w/w) Tween 80, pH 5 or
      7) at a mixing ratio of 1 : 1. Optical microscopy and static light scattering
      measurements indicated that emulsions were physically stable for 21 days, except
      for the slight aggregation of emulsions with a mean droplet size d43 of 4500 nm.
      The droplet size of hexadecane-in-water emulsions containing rosemary extract had
      no influence on the formation of lipid hydroperoxides at pH 5 and 7.
      Significantly lower concentrations of propanal were observed for the emulsions
      loaded with rosemary extract with a mean droplet size d43 of 4500 nm from day 12
      to 16 at pH 7. Finally, hexadecane-in-water emulsions containing rosemary extract
      significantly retarded lipid oxidation of fish oil-in-water emulsions in mixed
      systems, but no differences in antioxidant efficacy between the differently sized
      emulsions were observed at pH 5.

PMID- 25586116
TI  - Gasless laparoendoscopic single-port clampless sutureless partial nephrectomy for
      peripheral renal tumors: perioperative outcomes.
AB  - OBJECTIVES: To describe the technical aspects of gasless laparoendoscopic single
      port clampless sutureless partial nephrectomy for peripheral renal tumors, and to
      evaluate its outcomes, including surgical, pathological, and short-term
      oncological and functional outcomes. METHODS: Between January 2010 and June 2013,
      103 patients with peripheral renal tumors suggestive of renal cell carcinoma
      underwent gasless laparoendoscopic single-port partial nephrectomy. In all cases,
      an attempt was made to accomplish partial nephrectomy without vascular clamping
      using ultrasonic coagulating and bipolar sealing devices. Hemostasis was achieved
      by coagulation and hemostatic agents without reconstructing the renal parenchyma.
      RESULTS: Of the 103 patients, gasless laparoendoscopic single-port partial
      nephrectomy was accomplished without vascular clamping and parenchymal suture in
      all but two patients (98%). Median operative time and blood loss were 191 min and
      244 mL, respectively. One patient (1%) received allogeneic blood transfusion. The
      median postoperative time to full recovery was 3 days. Three major complications
      (3%, all grade 3 urinary leakage) were observed. Of 92 renal cell carcinoma
      patients, four (4%) had positive surgical margins, most of which underwent
      thermal degeneration histologically. In 91 non-metastatic renal cell carcinoma
      patients, 3-year local recurrence-free, progression-free, cancer-specific and
      overall survival rates were 100%, 99%, 100%, and 100%, respectively (mean follow
      up period, 21 months). In the 103 patients, the median percent decrease in
      estimated glomerular filtration rate 3 months after partial nephrectomy was 2.4%.
      CONCLUSIONS: Gasless laparoendoscopic single-port clampless sutureless partial
      nephrectomy can be accomplished in almost all cases of peripheral renal tumors.
      This surgery is technically feasible and safe, yielding acceptable short-term
      oncological outcomes and maximal preservation of renal function.

PMID- 25586119
TI  - Successful stenting of left pulmonary veins stenosis resulting from fibrosing
      mediastinitis.

PMID- 25586120
TI  - The world's longest follow-up after percutaneous coronary intervention, 37 years
      and still going strong.

PMID- 25586118
TI  - Ectoenzyme switches the surface of magnetic nanoparticles for selective binding
      of cancer cells.
AB  - Enzymatic switch, such as phosphorylation and dephosphorylation of proteins, is
      the most important mechanism for cellular signal transductions. Inspired by
      Nature and encouraged by our recent unexpected observation of the
      dephosphorylation of d-tyrosine phosphate-contain small peptides, we modify the
      surface of magnetic nanoparticles (MNP) with d-tyrosine phosphate that is a
      substrate of alkaline phosphatase (ALP). Our studies find that ALP is able to
      remove the phosphate groups from the magnetic nanoparticles. Most importantly,
      placental alkaline phosphatase (ALPP), an ectoenzyme that locates on cell surface
      with catalytic domains outside the plasma membrane and is overexpressed on many
      cancer cells, dephosphorylate the d-tyrosine phosphates on the surface of the
      magnetic nanoparticle and enable the magnetic nanoparticles to adhere selectively
      to the cancer cells, such as HeLa cells. Unlikely commonly used antibodies, the
      selectivity of the magnetic nanoparticles to cancer cells originates from the
      enzymatic reaction catalyzed by ALPP. The use of enzymatic reaction to modulate
      the surface of various nanostructures may lead to a general method to broadly
      target cancer cells without relying on specific ligand-receptor interactions
      (e.g., antibodies). This work, thus, illustrates a fundamentally new concept to
      allow cells to actively engineer the surface of colloids materials, such as
      magnetic nanoparticles, for various applications. 

PMID- 25586117
TI  - Immunosuppressive effects of Amblyomma cajennense tick saliva on murine bone
      marrow-derived dendritic cells.
AB  - BACKGROUND: Dendritic cells (DCs) are professional antigen-presenting cells with
      vital roles in the activation of host immunity. Ticks are bloodsucking arthropods
      that secrete bioactive compounds with immunomodulatory properties via their
      saliva. It is known that some tick species modulate the biology of DCs with
      different intensities; however, studies on Amblyomma cajennense, the Cayenne
      tick, have not yet been performed, although this species is considered one of the
      most capable of modulating immune responses of different hosts. METHODS: Engorged
      female ticks were stimulated with dopamine to induce salivation, and saliva was
      pooled. The effects of tick saliva on the biology of dendritic cells were
      assessed by examining DC differentiation, maturation, migration, cellular
      viability, cytokine production and expression of surface markers by flow
      cytometry and ELISA. Competitive enzyme immunoassays (EIA) were used to measure
      saliva prostaglandin-E2 (PGE2). Statistical significance was determined by ANOVA
      followed by Tukey's post-test or by the Kruskal-Wallis test with the Dunns post
      test. RESULTS: In this work, we demonstrated that the presence of A. cajennense
      saliva to bone marrow cultures inhibit DC differentiation. This inhibition was
      not accompanied by inhibition or induction of stimulatory and co-stimulatory
      molecules such as MHC-II, CD40, CD80 or CD86. Immature and mature DCs that were
      pre-exposed to saliva showed reduced migration toward the chemokines RANTES and
      MIP-3beta. This inhibition was associated to a reduced expression of CCR5 (the
      receptor for RANTES) or CCR7 (the receptor for MIP-3beta) induced by the presence
      of saliva in the cultures. Tick saliva also inhibited IL-12p40, IL-6 and TNF
      alpha in a concentration-dependent manner while potentiating IL-10 cytokine
      production by DCs stimulated with Toll-like receptor-4 ligand. Additionally, A.
      cajennense tick saliva inhibited the expression of CD40 and CD86 in mature DCs
      while potentiating the expression of PD-L1. PGE2 was detected as one of the
      constituents of saliva at a concentration of ~ 80 ng/ml, and we believe that most
      of the results reported herein are due to the presence of PGE2. CONCLUSIONS:
      These results help to understand the tick-host interaction and demonstrate that
      A. cajennense ticks appear to have mechanisms for modulating host immune cells,
      including DCs.

PMID- 25586121
TI  - Simulation in cardiology: state of the art.

PMID- 25586122
TI  - Isolated cardiac sarcoidosis: critical role of cardiac MRI for diagnosis and
      management.

PMID- 25586123
TI  - Cardiovascular risk in post-myocardial infarction patients: nationwide real world
      data demonstrate the importance of a long-term perspective.
AB  - AIMS: Long-term disease progression following myocardial infarction (MI) is not
      well understood. We examined the risk of subsequent cardiovascular events in
      patients discharged after MI in Sweden. METHODS AND RESULTS: This was a
      retrospective, cohort study linking morbidity, mortality, and medication data
      from Swedish national registries. Of 108 315 patients admitted to hospital with a
      primary MI between 1 July 2006 and 30 June 2011 (index MI), 97 254 (89.8%) were
      alive 1 week after discharge and included in this study. The primary composite
      endpoint of risk for non-fatal MI, non-fatal stroke, or cardiovascular death was
      estimated for the first 365 days post-index MI and Day 366 to study completion.
      Risk and risk factors were assessed by Kaplan-Meier analysis and Cox proportional
      hazards modelling, respectively. Composite endpoint risk was 18.3% during the
      first 365 days post-index MI. Age [60-69 vs. <60 years: HR (95% CI): 1.37 (1.30
      1.45); 70-79 vs. <60 years: 2.13 (2.03-2.24); >80 vs. <60 years: 3.96 (3.78
      4.15)], prior MI [1.44 (1.40-1.49)], stroke [1.49 (1.44-1.54)], diabetes [1.37
      (1.34-1.40)], heart failure [1.57 (1.53-1.62)] and no index MI revascularisation
      [1.88 (1.83-1.93)] were each independently associated with a higher risk of
      ischaemic events or death. For patients without a combined endpoint event during
      the first 365 days, composite endpoint risk was 20.0% in the following 36 months.
      CONCLUSIONS: Risk of cardiovascular events appeared high beyond the first year
      post-MI, indicating a need for prolonged surveillance, particularly in patients
      with additional risk factors.

PMID- 25586124
TI  - Transition to propofol after sevoflurane anesthesia to prevent emergence
      agitation: a randomized controlled trial.
AB  - BACKGROUND: Emergence agitation (EA) is a common behavioral disturbance after
      sevoflurane anesthesia in children. Propofol 1 mg . kg(-1) bolus at the end of
      sevoflurane anesthesia has had mixed results in reducing the incidence of EA,
      whereas propofol infusion throughout anesthesia maintenance seems effective but
      is more complex to administer. If a simple, short transition to propofol
      anesthesia was found to be effective in reducing EA, this could enhance the
      recovery of children following sevoflurane anesthesia. We therefore aimed to
      determine whether transition to propofol over 3 min at the end of sevoflurane
      anesthesia reduces the incidence of EA in children. METHODS: In this prospective
      randomized controlled trial, 230 children aged 1-12 years, undergoing magnetic
      resonance imaging (MRI) scans under sevoflurane anesthesia were randomized to
      receive either propofol 3 mg . kg(-1) over 3 min (propofol group), or no propofol
      (control group), at the end of sevoflurane anesthesia. EA was assessed by a
      blinded assessor using the Pediatric Emergence Anesthesia Delirium (PAED) scale
      and the Watcha scale until 30 min after emergence. EA on the PAED scale was
      defined as a PAED score >12. EA on the Watcha scale was defined as a score >= 3.
      Times to emergence, postanesthesia care unit (PACU) discharge, and discharge home
      were also recorded. RESULTS: Data were analyzed for 218 children. The incidence
      of EA was lower in the propofol group on both PAED (29% vs 7%; relative risk =
      0.25; 95% confidence interval 0.12-0.52; P < 0.001) and Watcha (39% vs 15%;
      relative risk = 0.37; 95% confidence interval 0.22-0.62; P < 0.001) scales.
      Duration and severity of EA were also reduced in the propofol group. Preplanned
      subgroup analyses for midazolam premedication, preexisting cognitive or
      behavioral disturbance, and age group did not alter our findings. Emergence time
      and time in PACU were both increased by a mean of 8 min in the propofol group (P
      < 0.001) with no difference in time to discharge home. CONCLUSIONS: Transition to
      propofol at the end of sevoflurane anesthesia reduces the incidence of EA and
      improves the quality of emergence. There is a small increase in recovery time,
      but no delay in discharge home.

PMID- 25586125
TI  - MiRNA-542-3p downregulation promotes trastuzumab resistance in breast cancer
      cells via AKT activation.
AB  - Trastuzumab (Herceptin) has been widely used in breast cancer treatment. However,
      the majority of cancers that initially respond to trastuzumab begin to progress
      again within 1 year. Despite the high resistance rate, the molecular mechanisms
      underlying this desease are not well understood. In the present study, microRNA
      (miRNA-542-3p modulated trastuzumab resistance in SKBR3 and MCF7/Her2 breast
      cancer cell lines. Trastuzumab induced miRNA-542-3p expression in SKBR3 and
      MCF7/Her2 cells. Furthermore, knockdown of miRNA-542-3p in the two cell lines
      resulted in decreased drug sensitivity to trastuzumab and cell apoptosis. The
      blockage of G1/S checkpoint by trastuzumab was rescued as well. miRNA-542-3p
      knockdown also activated the phosphatidylinositol 3-kinase (PI3K)-Akt pathway,
      while LY294002 reversed the effect of miRNA-542-3p knockdown. In summary, the
      results suggested that miRNA-542-3p downregulation may contribute to the
      trastuzumab resistance in breast cancer via, at least in part, the PI3K-akt
      pathway. Our findings provide new molecular mechanisms in trastuzumab resistance.

PMID- 25586127
TI  - Miniaturized quantum semiconductor surface plasmon resonance platform for
      detection of biological molecules.
AB  - The concept of a portable, inexpensive and semi-automated biosensing platform, or
      lab-on-a-chip, is a vision shared by many researchers and venture industries.
      Under this scope, we have investigated the application of optical emission from
      quantum well (QW) microstructures for monitoring surface phenomena on gold layers
      remaining in proximity (<300 nm) with QW microstructures. The uncollimated QW
      radiation excites surface plasmons (SP) and through the surface plasmon resonance
      (SPR) effect allows for detection of small perturbation in the density surface
      adsorbates. The SPR technology is already commonly used for biochemical
      characterization in pharmaceutical industries, but the reduction of the distance
      between the SP exciting source and the biosensing platform to a few hundreds of
      nanometers is an innovative approach enabling us to achieve an ultimate
      miniaturization of the device. We evaluate the signal quality of this
      nanophotonic QW-SPR device using hyperspectral-imaging technology, and we compare
      its performance with that of a standard prism-based commercial system. Two
      standard biochemical agents are employed for this characterization study: bovine
      serum albumin and inactivated influenza A virus. With an innovative conical
      method of SPR data collection, we demonstrate that individually collected SPR
      scan, each in less than 2.2 s, yield a resolution of the detection at 1.5 * 10-6
      RIU. 

PMID- 25586126
TI  - DNA/RNA Detection Using DNA-Templated Few-Atom Silver Nanoclusters.
AB  - DNA-templated few-atom silver nanoclusters (DNA/Ag NCs) are a new class of
      organic/inorganic composite nanomaterials whose fluorescence emission can be
      tuned throughout the visible and near-IR range by simply programming the template
      sequences. Compared to organic dyes, DNA/Ag NCs can be brighter and more
      photostable. Compared to quantum dots, DNA/Ag NCs are smaller, less prone to
      blinking on long timescales, and do not have a toxic core. The preparation of
      DNA/Ag NCs is simple and there is no need to remove excess precursors as these
      precursors are non-fluorescent. Our recent discovery of the fluorogenic and color
      switching properties of DNA/Ag NCs have led to the invention of new molecular
      probes, termed NanoCluster Beacons (NCBs), for DNA detection, with the capability
      to differentiate single-nucleotide polymorphisms by emission colors. NCBs are
      inexpensive, easy to prepare, and compatible with commercial DNA synthesizers.
      Many other groups have also explored and taken advantage of the environment
      sensitivities of DNA/Ag NCs in creating new tools for DNA/RNA detection and
      single-nucleotide polymorphism identification. In this review, we summarize the
      recent trends in the use of DNA/Ag NCs for developing DNA/RNA sensors. 

PMID- 25586128
TI  - The Heme-Based Oxygen-Sensor Phosphodiesterase Ec DOS (DosP): Structure-Function
      Relationships.
AB  - Escherichia coli Direct Oxygen Sensor (Ec DOS, also known as Ec DosP) is a heme
      based O2-sensing phosphodiesterase from Escherichia coli that catalyzes the
      conversion of cyclic-di-GMP to linear di-GMP. Cyclic-di-GMP is an important
      second messenger in bacteria, highlighting the importance of understanding
      structure-function relationships of Ec DOS. Ec DOS is composed of an N-terminal
      heme-bound O2-sensing PAS domain and a C-terminal phosphodiesterase catalytic
      domain. Notably, its activity is markedly enhanced by O2 binding to the heme
      Fe(II) complex in the PAS sensor domain. X-ray crystal structures and
      spectroscopic and catalytic characterization of the wild-type and mutant proteins
      have provided important structural and functional clues to understanding the
      molecular mechanism of intramolecular catalytic regulation by O2 binding. This
      review summarizes the intriguing findings that have obtained for Ec DOS. 

PMID- 25586129
TI  - Impaired visual inhibition in migraine with aura.
AB  - OBJECTIVE: The pathophysiology of migraine with or without aura (MA, MO) is still
      a matter of debate. We thus studied patients with MA and MO by means of paired
      pulse flash-visual evoked potentials (paired F-VEPs). This technique, recently
      revived, analyses the overall excitability of visual system as detected from the
      cortical occipital signal. METHODS: We enrolled 13 adult patients with MO and 13
      with MA. Twenty-two normal subjects of similar age and sex acted as controls.
      Stimuli were single flashes, intermingled at random to flash pairs at critical
      interstimulus intervals (ISIs, 16.5-125ms) with closed and open eyes. The
      "single"(unconditioned) F-VEP was split into a "main complex" (50-200ms after the
      flash) and a "late response" (200-400ms). As for paired stimulation, the "test" F
      VEP emerged from electronic subtraction of the "single" F-VEP to the "paired" F
      VEP. Its size was expressed as "test"/"single"F-VEP*100. RESULTS: As for paired F
      VEPs, the "main complex" of the "test" F-VEP in the MA group did not show the
      size reduction (at ISIs 50-62.5ms) which was typical among the control and MO
      groups (p?0.016) in the "eyes-closed" state. CONCLUSIONS: Paired F-VEPs document
      a defective neural inhibition in the visual system of patients with MA.
      SIGNIFICANCE: Paired F-VEPs may warrant inclusion in future preclinical/clinical
      studies, to evaluate its potential role in the pathophysiology and management of
      MA.

PMID- 25586130
TI  - Using Roadside Billboard Posters to Increase Admission Rates to Problem Gambling
      Services: Reflections on Failure.
AB  - Based on the stimulus-response model of advertising, this study sought to
      increase admission rates to a local problem gambling service (PGS) in Windsor,
      Ontario, Canada, by adding a series of locally based 10 foot by 20 foot roadside
      billboard posters to PGS's existing communications tools for a 24-week period.
      Using proof of performance reports, a pre-post survey of new callers to PGS, a
      website visit counter, and a media awareness survey, the findings showed that at
      least some individuals were influenced by billboard exposure, but admission rates
      continued to decline during the billboard campaign period. While one possible
      explanation for the communications failure was that the whole PGS communications
      campaign was below the minimal threshold for communications perception, another
      possible explanation is that the stimulus-response model of advertising used may
      not have been appropriate for such advertising that targets behavior change.
      Reflections on using an information-processing model instead of a stimulus
      response model, and considerations of a two-step flow of communication, are
      provided. Recommendations are made regarding matching communications messages to
      stages of behavior change, use of online promotion, and strategies for future
      research. 

PMID- 25586131
TI  - Vision impaired or professionally blind: health education research and firearm
      violence.
AB  - In the past three decades, approximately 1 million Americans have been killed
      with firearms and over 2 million have been injured with firearms. Firearm
      violence is one of the top 10 causes of premature mortality for racial/ethnic
      minorities and youths 1 to 19 years of age. However, firearm violence issues are
      virtually absent in the past 15 years in health education-related journals. We
      provide several examples of areas of health education where firearm violence is
      congruent with the professional responsibilities of health educators. Finally, we
      encourage health educators to become involved in firearm violence research and
      health education-related journal leaders to become more proactive in soliciting
      manuscripts that address firearm violence-related issues. 

PMID- 25586133
TI  - Health Promotion Text Messaging Preferences and Acceptability Among the Medically
      Underserved.
AB  - The Colorado Healthy Heart Solutions program uses community health workers to
      provide health promotion and navigation services for participants in medically
      underserved, predominantly rural areas who are at risk for developing
      cardiovascular disease. A text messaging program designed to increase participant
      engagement and adherence to lifestyle changes was pilot tested with English- and
      Spanish-speaking participants. Preimplementation focus groups with participants
      informed the development of text messages that were used in a 6-week pilot
      program. Postimplementation focus groups and interviews then evaluated the pilot
      program. Participants reported a preference for concise messages received once
      daily and for positive messages suggesting specific actions that could be
      feasibly accomplished within the course of the day. Participants also
      consistently reported the desire for clarity in message delivery and content,
      indicating that the source of the messages should be easy to recognize, messages
      should state clearly when participants were expected to respond to the messages,
      and any responses should be acknowledged. Links to other websites or resources
      were generally viewed as trustworthy and acceptable, but were preferred for
      supplementary material only. These results may inform the development of future
      chronic disease management programs in underserved areas or augment existing
      programs using text messaging reinforcement. 

PMID- 25586132
TI  - Physical activity opportunities in afterschool programs.
AB  - Afterschool programs (ASPs) have potential to provide children moderate to
      vigorous physical activity (MVPA). The availability and types (e.g., free play or
      organized activities) of physical activity opportunities, their structure (e.g.,
      presence of lines, elimination games), and staff behaviors (e.g., encouragement,
      engaged) can influence children's MVPA. This study explored these factors in 20
      ASPs serving over 1,700 elementary-age children. The occurrence, types, and
      structure of physical activity opportunities, and staff behaviors were collected
      via the SOSPAN (System for Observing Staff Promotion of Physical Activity and
      Nutrition). A total of 4,660 SOSPAN scans were completed across 63 complete
      program days (1,733 during physical activity opportunities). Physical activity
      opportunities were observed on 60 program days across all 20 sites, with 73% of
      those opportunities classified as free play. ASPs scheduled an average of 66.3
      minutes (range 15-150 minutes) of physical activity opportunities daily. Games
      played included basketball, tag, soccer, and football. Staff rarely engaged in
      physical activity promotion behaviors, and the structure of organized games
      discouraged MVPA. For example, staff verbally promoted physical activity in just
      6.1% of scans, while organized games were more likely to involve lines and
      elimination. Professional development training may enhance staffs' physical
      activity promotion and the structure of activity opportunities. 

PMID- 25586134
TI  - Isolation of a novel antibacterial phenyl thioketone from the seagrass, Cymodocea
      serrulata.
AB  - A total of 40 extract types of varying polarities from commonly occurring
      seagrasses were tested for their antibacterial efficiency against 14 clinically
      isolated human pathogens using agar well diffusion technique. The extracts from
      acetone of Cymodocea serrulata expressed moderate broad span of activity against
      a range of gram-positive and gram-negative isolates that were at least resistant
      to five of the commercially available antibiotics at a minimal concentration of
      10 ug. The active extracts of C. serrulata that showed maximal inhibitions were
      purified using column chromatography that afforded six compounds (a-f). Compound
      f elicited pronounced inhibitions against Escherichia coli with minimal
      inhibitory concentration values of 1-3 ug concentration using micro-dilution
      method. The active compound was identified as phenyl thioketone using various
      spectral analyses. This is the first investigation that reveals thioketone
      functionality from this seagrass species possessing antibacterial actions. This
      study indicates that there are thiocarbonyl groups from marine floral sources
      too, which could be possibly used for therapeutic purposes.

PMID- 25586135
TI  - Religion, Spirituality and Speech-Language Pathology: A Viewpoint for Ensuring
      Patient-Centred Holistic Care.
AB  - This paper presents a viewpoint concerning the largely neglected clinical
      relevance of spirituality and religious belief in speech-language pathology (SLP)
      assessments, interventions and outcomes across the lifespan. An overview of the
      refereed SLP literature is presented with regard to religion and spirituality. It
      was found that while there is increasing research with regard to spirituality,
      health and well-being, there is very little specific to SLP. What is available
      and clinically relevant, generally relates to holistic care and/or cultural and
      linguistic diversity. Amidst the health care literature, however, there is a
      growing number of recommended instruments (for religious/spiritual screening)
      sensitive to intercultural and interfaith issues that are currently available to
      medical, nursing, allied health and chaplaincy practitioners. These instruments
      can also be of value to SLPs to ensure holistic assessments and interventions. It
      would seem timely for SLPs (and other allied health practitioners) to consider
      including spiritual screenings/assessments as part of their clinical practice so
      as to ensure appropriate holistic care. This would also mean undertaking research
      and including relevant education within tertiary institutions and professional
      development programs. 

PMID- 25586136
TI  - Biosynthetic labeling and two-color imaging of phospholipids in cells.
AB  - Phospholipids with a choline head group are abundant components of all biological
      membranes, performing critical functions in cellular structure, metabolism, and
      signaling. In spite of their importance, our ability to visualize choline
      phospholipids in vivo remains very limited. We present a simple and robust
      chemical strategy to image choline phospholipids, based on the metabolic
      incorporation of azidocholine analogues, that accurately reflects the normal
      biosynthetic incorporation of choline into cellular phospholipids. Azidocholine
      labeled phospholipids can be imaged in cells with high sensitivity and
      resolution, following derivatization with fluorophores, by bio-orthogonal
      chemical reactions compatible with live-cell imaging. We used this method to
      visualize the subcellular localization of choline phospholipids. We also
      demonstrate that double metabolic labeling with azidocholine and propargylcholine
      allows sensitive two-color imaging of choline phospholipids. Our method
      represents a powerful approach to directly image phospholipids, and to study
      their dynamics in cells and tissues. 

PMID- 25586137
TI  - Visualization of an evaporating thin layer during the evaporation of a nanofluid
      droplet.
AB  - During the evaporation of a droplet, there exists an evaporating thin layer that
      is difficult to visualize because of optical restrictions. The present study
      visualized this thin layer by using a reflective-mode, confocal microscope that
      can provide improved signal-to-noise focal plane imaging over traditional optical
      microscopy while simultaneously serving as an interferometer when imaging thin
      liquid films. The spatial distribution of the evaporating thin layer thickness
      was determined from interferometric fringe analysis. Three distinct fringe
      patterns, or regions, were observed depending on the nanoparticle concentration.
      These regions are referred to as uniform, slow extension, and rapid extension.
      The formation of the three regions is closely associated with the variation of
      the evaporating thin layer thickness of a nanofluid droplet. The nanoparticle
      bank formed near the contact line region substantially affects the rate of change
      in the evaporating thin layer thickness that increases with the nanoparticle
      concentration. 

PMID- 25586138
TI  - Preparation and characterization of a decellularized cartilage scaffold for ear
      cartilage reconstruction.
AB  - Scaffolds are widely used to reconstruct cartilage. Yet, the fabrication of a
      scaffold with a highly organized microenvironment that closely resembles native
      cartilage remains a major challenge. Scaffolds derived from acellular
      extracellular matrices are able to provide such a microenvironment. Currently, no
      report specifically on decellularization of full thickness ear cartilage has been
      published. In this study, decellularized ear cartilage scaffolds were prepared
      and extensively characterized. Cartilage decellularization was optimized to
      remove cells and cell remnants from elastic cartilage. Following removal of
      nuclear material, the obtained scaffolds retained their native collagen and
      elastin contents as well as their architecture and shape. High magnification
      scanning electron microscopy showed no obvious difference in matrix density after
      decellularization. However, glycosaminoglycan content was significantly reduced,
      resulting in a loss of viscoelastic properties. Additionally, in contact with the
      scaffolds, human bone-marrow-derived mesenchymal stem cells remained viable and
      are able to differentiate toward the chondrogenic lineage when cultured in vitro.
      These results, including the ability to decellularize whole human ears, highlight
      the clinical potential of decellularization as an improved cartilage
      reconstruction strategy. 

PMID- 25586139
TI  - The nuclear splicing factor RNA binding motif 5 promotes caspase activation in
      human neuronal cells, and increases after traumatic brain injury in mice.
AB  - Splicing factors (SFs) coordinate nuclear intron/exon splicing of RNA. Splicing
      factor disturbances can cause cell death. RNA binding motif 5 (RBM5) and 10
      (RBM10) promote apoptosis in cancer cells by activating detrimental alternative
      splicing of key death/survival genes. The role(s) of RBM5/10 in neurons has not
      been established. Here, we report that RBM5 knockdown in human neuronal cells
      decreases caspase activation by staurosporine. In contrast, RBM10 knockdown
      augments caspase activation. To determine whether brain injury alters RBM
      signaling, we measured RBM5/10 protein in mouse cortical/hippocampus homogenates
      after controlled cortical impact (CCI) traumatic brain injury (TBI) plus
      hemorrhagic shock (CCI+HS). The RBM5/10 staining was higher 48 to 72 hours after
      injury and appeared to be increased in neuronal nuclei of the hippocampus. We
      also measured levels of other nuclear SFs known to be essential for cellular
      viability and report that splicing factor 1 (SF1) but not splicing factor 3A
      (SF3A) decreased 4 to 72 hours after injury. Finally, we confirm that RBM5/10
      regulate protein expression of several target genes including caspase-2, cellular
      FLICE-like inhibitory protein (c-FLIP), LETM1 Domain-Containing Protein 1
      (LETMD1), and amyloid precursor-like protein 2 (APLP2) in neuronal cells.
      Knockdown of RBM5 appeared to increase expression of c-FLIP(s), LETMD1, and APLP2
      but decrease caspase-2.

PMID- 25586140
TI  - Enhanced delivery and bioactivity of the neurturin neurotrophic factor through
      focused ultrasound-mediated blood--brain barrier opening in vivo.
AB  - The blood-brain barrier (BBB) constitutes a major obstacle in brain drug
      delivery. Focused ultrasound (FUS) in conjunction with microbubbles has been
      shown to open the BBB noninvasively, locally, and transiently to allow large
      molecules diffusion. Neurturin (NTN), a member of the glial-derived neurotrophic
      factor (GDNF) family, has been demonstrated to have neuroprotective and
      regenerative effects on dopaminergic neurons in vivo using invasive drug delivery
      methods. The brain's ascending nigrostriatal pathway is severely damaged in
      Parkinson's disease (PD), and therefore the substantia nigra (SN) and striatal
      caudoputamen (CP) were selected as the target areas. The objective of the study
      was to investigate whether safe and efficient NTN delivery can be achieved
      through FUS-induced BBB opening via intravenous administration, and thus trigger
      the neuroregeneration cascade in the nigrostriatal pathway. After the
      optimization of FUS parameters and target locations in the murine brain, NTN
      bioavailability and downstream signaling were detected and characterized through
      immunostaining. FUS significantly enhanced the delivery of NTN compared with the
      direct injection technique, whereas triggering of the signaling cascade was
      detected downstream to the neuronal nuclei. These findings thus indicate the
      potential of the FUS method to mediate transport of proteins through the blood
      brain barrier in a PD animal model. 

PMID- 25586142
TI  - Noninvasive real-time visualization of multiple cerebral hemodynamic parameters
      in whole mouse brains using five-dimensional optoacoustic tomography.
AB  - Current functional neuroimaging methods are not adequate for high-resolution
      whole-brain visualization of neural activity in real time. Here, we show imaging
      of fast hemodynamic changes in deep mouse brain using fully noninvasive
      acquisition of five-dimensional optoacoustic data from animals subjected to
      oxygenation stress. Multispectral video-rate acquisition of three-dimensional
      tomographic data enables simultaneous label-free assessment of multiple brain
      hemodynamic parameters, including blood oxygenation, total hemoglobin, cerebral
      blood volume, oxygenized and deoxygenized hemoglobin, in real time. The
      unprecedented results indicate that the proposed methodology may serve as a
      powerful complementary, and potentially superior, method for functional
      neuroimaging studies in rodents. 

PMID- 25586141
TI  - TAK-242, an antagonist for Toll-like receptor 4, protects against acute cerebral
      ischemia/reperfusion injury in mice.
AB  - Toll-like receptor 4 (TLR4) contributes to cerebral ischemia/reperfusion (I/R)
      injury and is a potential target for the treatment of ischemic stroke. This
      experiment is to evaluate the effect of an exogenous TLR4 antagonist, TAK-242,
      against acute cerebral I/R injury. A mouse model of cerebral I/R was induced by
      transient middle cerebral artery occlusion. TAK-242 (3 mg/kg body weight) was
      injected intraperitoneally 1 hour after ischemia. Our results showed that the
      concentration of TAK-242 in plasma increased to 52.0 ng/mL 3 hours after
      injection, was maintained at 54.1 ng/mL 8 hours after injection, and decreased to
      22.6 ng/mL 24 hours after injection. The concentration of TAK-242 in brain tissue
      increased to 26.1 ng/mL in ischemic hemisphere and 14.2 ng/mL in nonischemic
      hemisphere 3 hours after injection, and was maintained at the similar levels 24
      hours after injection. We found that TAK-242 significantly reduced cerebral
      infarction compared with vehicle control, improved neurologic function, inhibited
      the phosphorylation of downstream protein kinases in TLR4 signaling pathway, and
      downregulated the expression of inflammatory cytokines. We conclude that TAK-242
      is able to cross blood-brain barrier, blocks TLR4 signaling, mediates the
      expression of inflammatory cytokines, and protects the brain from acute damage
      induced by I/R.

PMID- 25586143
TI  - Sex-associated differences in the modulation of vascular risk in patients with
      asymptomatic carotid stenosis.
AB  - In this study, we aimed to identify determinants of the different sex-related
      stroke risk in subjects with asymptomatic internal carotid artery (ICA) stenosis.
      In all, 492 women (44.4%) and 617 men (55.6%), with unilateral ? 60% asymptomatic
      ICA stenosis, were prospectively evaluated with a median follow-up of 37 months
      (interquartile range, 26 to 43). Vascular risk profile, plaque characteristics,
      stenosis progression, and common carotid artery intima-media thickness were
      investigated. Outcome measure was the occurrence of ischemic stroke ipsilateral
      to ICA stenosis. Myocardial infarction, contralateral stroke and transient
      ischemic attack were considered as competing events. The incidence rate of
      ipsilateral stroke over the entire follow-up period was 0.16%: 0.09% (95%
      confidence interval (CI) 0.05 to 0.15) in women and 0.22% (95% CI 0.17 to 0.29)
      in men (log-rank test, P<0.001). Stenosis progression significantly influenced
      the risk of ipsilateral stroke in both men (subhazard ratio, SHR, 8.99) and women
      (SHR 4.89). Stenosis degree (71% to 90%, SHR 2.35; 91% to 99%, SHR 3.38) and
      irregular plaque surface (SHR 2.32) were relevant risk factors for ipsilateral
      stroke only in men. Our findings suggest that characteristics of the stenosis and
      plaque exert a different effect in modulating vascular risk in the two sexes.
      Understanding sex differences in cardiovascular disease could help to target sex
      specific future therapies.

PMID- 25586144
TI  - Therapeutic hypothermia achieves neuroprotection via a decrease in acetylcholine
      with a concurrent increase in carnitine in the neonatal hypoxia-ischemia.
AB  - Although therapeutic hypothermia is known to improve neurologic outcomes after
      perinatal cerebral hypoxia-ischemia, etiology remains unknown. To decipher the
      mechanisms whereby hypothermia regulates metabolic dynamics in different brain
      regions, we used a two-step approach: a metabolomics to target metabolic pathways
      responding to cooling, and a quantitative imaging mass spectrometry to reveal
      spatial alterations in targeted metabolites in the brain. Seven-day postnatal
      rats underwent the permanent ligation of the left common carotid artery followed
      by exposure to 8% O2 for 2.5 hours. The pups were returned to normoxic conditions
      at either 38  degrees C or 30  degrees C for 3 hours. The brain metabolic states
      were rapidly fixed using in situ freezing. The profiling of 107 metabolites
      showed that hypothermia diminishes the carbon biomass related to acetyl moieties,
      such as pyruvate and acetyl-CoA; conversely, it increases deacetylated
      metabolites, such as carnitine and choline. Quantitative imaging mass
      spectrometry demarcated that hypothermia diminishes the acetylcholine contents
      specifically in hippocampus and amygdala. Such decreases were associated with an
      inverse increase in carnitine in the same anatomic regions. These findings imply
      that hypothermia achieves its neuroprotective effects by mediating the cellular
      acetylation status through a coordinated suppression of acetyl-CoA, which resides
      in metabolic junctions of glycolysis, amino-acid catabolism, and ketolysis.

PMID- 25586145
TI  - Hyperperfusion counteracted by transient rapid vasoconstriction followed by long
      lasting oligemia induced by cortical spreading depression in anesthetized mice.
AB  - Cortical spreading depression (CSD) involves mass depolarization of neurons and
      glial cells accompanied with changes in regional cerebral blood flow (rCBF) and
      energy metabolism. To further understand the mechanisms of CBF response, we
      examined the temporal diametric changes in pial arteries, pial veins, and
      cortical capillaries. In urethane-anesthetized mice, the diameters of these
      vessels were measured while simultaneously recording rCBF with a laser Doppler
      flowmeter. We observed a considerable increase in rCBF during depolarization in
      CSD induced by application of KCl, accompanied by a transient dip of rCBF with
      marked vasoconstriction of pial arteries, which resembled the response to pin
      prick-induced CSD. Arterial constriction diminished or disappeared during the
      second and third passages of CSD, whereas the rCBF increase was maintained
      without a transient dip. Long-lasting oligemia with a decrease in the reciprocal
      of mean transit time of injected dye and mild constriction of pial arteries was
      observed after several passages of the CSD wave. These results indicate that CSD
      induced rCBF changes consist of initial hyperemia with a transient dip and
      followed by a long-lasting oligemia, partially corresponding to the diametric
      changes of pial arteries, and further suggest that vessels other than pial
      arteries, such as intracortical vessels, are involved. 

PMID- 25586147
TI  - Revitalizing condom-centered HIV prevention strategies.
AB  - HIV infection rates remain steady in the USA despite the numerous prevention
      programs and tools available. Condoms play a central role in HIV prevention
      because they are highly effective, readily available, and affordable.
      Unfortunately, condom promotion efforts often incite fear as a motive force,
      while also taking the common "one-size-fits-all" approach. Reframing condom
      promotion through a sexual health framework, focusing on pleasure and
      highlighting condom fit issues, improves intervention efficacy. Condom
      distribution policies may further perpetuate condom users' difficulty, by
      withholding particular condom styles, brands, and information highlighting the
      nuances in shape, size, and material. Condom education and distribution practices
      focused on pleasure, proper fit, and condom access issues might increase condom
      utilization among high-risk populations. 

PMID- 25586149
TI  - What is wrong with the right ventricle after surgical closure of a ventricular
      septal defect?

PMID- 25586146
TI  - Bioinformatics and HIV latency.
AB  - Despite effective treatment, HIV is not completely eliminated from the infected
      organism because of the existence of viral reservoirs. A major reservoir consists
      of infected resting CD4+ T cells, mostly of memory type, that persist over time
      due to the stable proviral insertion and a long cellular lifespan. Resting cells
      do not produce viral particles and are protected from viral-induced cytotoxicity
      or immune killing. However, these latently infected cells can be reactivated by
      stochastic events or by external stimuli. The present review focuses on novel
      genome-wide technologies applied to the study of integration, transcriptome, and
      proteome characteristics and their recent contribution to the understanding of
      HIV latency. 

PMID- 25586148
TI  - Suppressing spontaneous polarization of p-GaN by graphene oxide passivation:
      augmented light output of GaN UV-LED.
AB  - GaN-based ultraviolet (UV) LEDs are widely used in numerous applications,
      including white light pump sources and high-density optical data storage.
      However, one notorious issue is low hole injection rate in p-type transport layer
      due to poorly activated holes and spontaneous polarization, giving rise to
      insufficient light emission efficiency. Therefore, improving hole injection rate
      is a key step towards high performance UV-LEDs. Here, we report a new method of
      suppressing spontaneous polarization in p-type region to augment light output of
      UV-LEDs. This was achieved by simply passivating graphene oxide (GO) on top of
      the fully fabricated LED. The dipole layer formed by the passivated GO enhanced
      hole injection rate by suppressing spontaneous polarization in p-type region. The
      homogeneity of electroluminescence intensity in active layers was improved due to
      band filling effect. As a consequence, the light output was enhanced by 60% in
      linear current region. Our simple approach of suppressing spontaneous
      polarization of p-GaN using GO passivation disrupts the current state of the art
      technology and will be useful for high-efficiency UV-LED technology. 

PMID- 25586150
TI  - Testing For Measurement Invariance of Attachment Across Chinese and American
      Adolescent Samples.
AB  - Adolescent attachment to formal and informal institutions has emerged as a major
      focus of criminological theories since the publication of Hirschi's work in 1969.
      This study attempts to examine the psychometric equivalence of the factorial
      structure of attachment measures across nations reflecting Western and Eastern
      cultures. Twelve manifest variables are used tapping the concepts of adolescent
      attachment to parents, school, and neighborhood. Confirmatory factor analysis is
      used to conduct invariance test across approximately 3,000 Chinese and U.S.
      adolescents. Results provide strong support for a three-factor model; the
      multigroup invariance tests reveal mixed results. While the family attachment
      measure appears invariant between the two samples, significant differences in the
      coefficients of the factor loadings are detected in the school attachment and
      neighborhood attachment measures. The results of regression analyses lend support
      to the predictive validity of three types of attachment. Finally, the limitations
      of the study are discussed. 

PMID- 25586151
TI  - New evidence for the potential role of Culex pipiens mosquitoes in the
      transmission cycle of West Nile virus in Tunisia.
AB  - Physiological and molecular characteristics of natural populations of Culex
      pipiens Linnaeus, 1758 (Diptera: Culicidae) were investigated to elucidate how
      this species is potentially involved in the transmission of West Nile virus in
      Tunisia. A total of 215 Cx. pipiens females from 11 breeding habitats were
      analysed in the laboratory to estimate autogeny and stenogamy rates. They were
      tested individually for the locus CQ11 to distinguish between the two Cx. pipiens
      forms, pipiens and molestus. All tested Cx. pipiens populations were stenogamous.
      Females from underground breeding sites were all autogeneous, whereas females
      from above-ground habitats were mostly anautogeneous. Of all the females tested,
      59.7% were identified as pipiens, 22.4% as molestus, and 17.9% as hybrid
      pipiens/molestus. Furthermore, both Cx. pipiens forms and their hybrids were
      found to co-occur in sympatry in all sites. The results of this study represent
      the first evidence that both Cx. pipiens forms and their hybrids are present in
      Tunisia. Because hybrids able to act as bridge vectors are present in all studied
      habitats, Tunisia can be considered to have a high degree of receptivity for the
      establishment of West Nile virus zoonotic cycles.

PMID- 25586153
TI  - Aerosol generation by raindrop impact on soil.
AB  - Aerosols are investigated because of their significant impact on the environment
      and human health. To date, windblown dust and sea salt from sea spray through
      bursting bubbles have been considered the chief mechanisms of environmental
      aerosol dispersion. Here we investigate aerosol generation from droplets hitting
      wettable porous surfaces including various classifications of soil. We
      demonstrate that droplets can release aerosols when they influence porous
      surfaces, and these aerosols can deliver elements of the porous medium to the
      environment. Experiments on various porous media including soil and engineering
      materials reveal that knowledge of the surface properties and impact conditions
      can be used to predict when frenzied aerosol generation will occur. This study
      highlights new phenomena associated with droplets on porous media that could have
      implications for the investigation of aerosol generation in the environment. 

PMID- 25586152
TI  - Single- and multiple-dose pharmacokinetics and tolerability of limaprost in
      healthy Chinese subjects.
AB  - BACKGROUND AND OBJECTIVES: Limaprost, a prostaglandin E1 analogue, is used to
      treat various symptoms in patients with ischemic diseases. The present study was
      designed to determine the pharmacokinetics and tolerability of single and
      multiple oral doses of limaprost 5 MUg tablets in healthy Chinese subjects.
      METHODS: Single and multiple doses of 5-MUg limaprost were orally administered to
      12 healthy Chinese subjects. There was a 2-week washout period between single and
      multiple dosing. Blood samples were collected at various times. Indomethacin and
      aspirin were added to the blood samples to inhibit the endogenous release of
      prostaglandins during the sample processing. Plasma limaprost was measured by a
      two-dimensional liquid chromatography-tandem mass spectrometry method. RESULTS:
      After single dosing, limaprost was rapidly absorbed (time to reach maximum plasma
      concentration [t max] = 22.50 min) and eliminated (elimination half-life [t 1/2]
      = 21.70 min), with the maximum plasma concentration (C max) being 2.56 pg/mL and
      area under the concentration-time curve (AUC) from time 0 to the last
      quantifiable time point (AUC0-t) being 70.68 pg.min/mL. There were significant
      inter-individual variations in the AUCs for both single- and multiple-dose
      regimens. The values of C max, AUC, t 1/2 and t max were not statistically
      different between single and multiple dosing. The accumulation factor R was 0.609
      +/- 0.432 (R < 1), indicating that there was no accumulation after multiple
      dosing. There were no statistically significant differences in pharmacokinetic
      parameters for both single and multiple dosing between female and male subjects.
      The drug was well tolerated, with no severe adverse events being observed.
      CONCLUSIONS: Limaprost is rapidly absorbed after oral administration and is
      rapidly eliminated, with no accumulation after multiple dosing. The drug is well
      tolerated and no serious adverse events occurred.

PMID- 25586154
TI  - Diagnosis of an aortic valvular lesion. Non-bacterial thrombotic endocarditis
      (NBTE).

PMID- 25586155
TI  - Does TCPC power loss really affect exercise capacity?

PMID- 25586158
TI  - Better measures of fat mass - beyond BMI.

PMID- 25586156
TI  - Transcatheter aortic valve replacement and standard therapy in inoperable
      patients with aortic stenosis and low EF.
AB  - OBJECTIVES: The aims of this study were to evaluate the effect of left
      ventricular (LV) dysfunction on clinical outcomes after transcatheter aortic
      valve replacement (TAVR) and standard therapy for severe aortic stenosis (AS) and
      to assess LV ejection fraction (LVEF) recovery and its impact on subsequent
      clinical outcomes. METHODS: Cohort B of the Placement of AoRtic TraNscathetER
      Valves trial randomised 342 inoperable patients with severe AS to TAVR or
      standard therapy. We defined LV dysfunction as an LVEF <50% and LVEF improvement
      as an absolute increase in LVEF >=10% at 30 days. RESULTS: Baseline LV
      dysfunction did not affect survival after TAVR but was associated with increased
      cardiac mortality at 1 year with standard therapy (59.3% vs 45.8% with normal
      LVEF; HR=1.71 (95% CI 1.08 to 2.71); p=0.02). In those with LV dysfunction, LVEF
      improvement occurred in 48.7% and 30.4% of TAVR and standard therapy patients,
      respectively (p=0.08), and was independently predicted by relative wall thickness
      and receipt of TAVR. LVEF improvement with standard therapy portended reduced all
      cause mortality at 1 year (28.6% vs 65.6% without LVEF improvement; HR=0.32 (95%
      CI 0.11 to 0.93); p=0.03) but not at 2 years. CONCLUSIONS: In inoperable patients
      with severe AS, mild-to-moderate LV dysfunction is associated with higher cardiac
      mortality with standard therapy but not TAVR. A subset of patients undergoing
      standard therapy with LV dysfunction demonstrates LVEF improvement and favourable
      1-year but not 2-year survival. TAVR improves survival and should be considered
      the standard of care for inoperable patients with AS and LVEF >20%. TRIAL
      REGISTRATION NUMBER: ClinicalTrials.gov Unique Identifier #NCT00530894.

PMID- 25586159
TI  - Routine group and save unnecessary for gastric band surgery: a retrospective case
      review audit of 1018 bariatric patients.
AB  - What is already known about this subject *  The demand for bariatric surgery is
      increasing. *  NHS Trusts are expected to instigate cost-efficiency measures. * 
      Previous articles have discussed the need for routine preoperative cross-match.
      What this study adds *  No gastric band patient suffered a significant drop in
      haemoglobin or needed a blood transfusion. *  Group and save samples could be
      safely stored in the laboratory and only sent for analysis if clinically
      indicated. *  Even greater cost savings could be achieved if prudent use of
      perioperative blood testing and blood transfusion was implemented. SUMMARY:
      Current guidance at our Trust is that all bariatric surgical patients should have
      preoperative group and save (G&S) and full blood count (FBC) tests, as well as a
      FBC check 1 d post-operatively. Our aim was to investigate blood transfusion
      requirements of these patients and whether we could reduce the number of
      investigations requested. 1018 consecutive elective laparoscopic gastric band and
      laparoscopic Roux-en-Y gastric bypass patients who were operated on in our
      bariatric unit from March 2000 until January 2011 were identified. Patients'
      haemoglobin levels, G&S status and blood transfusion requirements were analyzed
      using our online pathology system. 607 patients had a laparoscopic gastric band,
      with 411 undergoing a laparoscopic Roux-en-Y gastric bypass. None of our gastric
      band patients required a transfusion; however, nine patients (2.2%) undergoing a
      gastric bypass needed a transfusion. Two patients required transfusion within 24
      h of surgery while six of the remaining seven patients received blood 3-4 d post
      operatively. Costs incurred on FBC and G&S tests during this time were estimated
      to exceed L15 700. G&S and post-operative FBC tests could be abandoned for
      laparoscopic gastric band patients with significant financial and person-time
      savings. However, given that 2.2% of laparoscopic Roux-en-Y gastric bypass
      patients needed a blood transfusion, we believe that post-operative FBC tests are
      still warranted in this patient group, with a G&S sample stored in pathology.
      Much greater financial savings could be achieved if prudent use of preoperative
      investigations, including storing G&S samples in the laboratory, was adopted for
      all elective operations.

PMID- 25586157
TI  - A practical approach to reporting treatment abandonment in pediatric chronic
      conditions.
AB  - Treatment abandonment, the failure to complete therapy that is required for
      definitive disease control, frequently causes treatment failure for pediatric
      patients in low- and middle-income countries with chronic conditions,
      particularly cancer. Other forms of incomplete treatment affecting children in
      all settings, such as nonadherence and loss to follow-up, are often confused with
      treatment abandonment. Unclear definitions of incomplete treatment dramatically
      affect reported outcomes. To facilitate disease-specific and cross-sector
      analyses, we outline a practical approach to categorize forms of incomplete
      treatment, present distinct semantic categories with case examples and provide an
      algorithm that could be tailored to disease- and context-specific needs.

PMID- 25586160
TI  - Realistic first steps for effectively managing obesity in Canada.

PMID- 25586161
TI  - Stagnation in the clinical, community and public health domain of obesity: the
      need for probative research.

PMID- 25586162
TI  - Lipedema: an overview of its clinical manifestations, diagnosis and treatment of
      the disproportional fatty deposition syndrome - systematic review.
AB  - Lipedema is a disproportionate, symmetrical fatty swelling characterized by pain
      and bruising existing almost exclusively among women. We undertook a systematic
      review of the available literature about lipedema, given the lack of knowledge
      and little evidence about this disorder especially among obesity experts.
      Diagnosis of lipedema is usually based on clinical features. Symmetrical edema in
      the lower limbs with fatty deposits located to hips and thighs usually appears at
      puberty and often affects several members of the same family. Main disorders
      considered for differential diagnosis are lymphedema, obesity, lipohypertrophy
      and phlebedema. Treatment protocols comprise conservative (decongestive lymphatic
      therapy) and surgical (liposuction) approaches. Early diagnosis and treatment are
      mandatory for this disorder otherwise gradual enlargement of fatty deposition
      causes impaired mobility and further comorbidities like arthrosis and lymphatic
      insufficiency. 

PMID- 25586163
TI  - Effective UK weight management services for adults.
AB  - A number of evidence-based weight management interventions are now available with
      different models and serving different patient/client groups. While positive
      outcomes are a key to the decision-making process, so too is the information
      around how these outcomes were achieved, in what population, how transferable the
      outcomes would be to the population a service would be aiming to cover and at
      what cost to the service provider and or the individual. This paper examines all
      the UK interventions with recent peer-reviewed evidence of their effectiveness in
      'realistic' settings and cost-effectiveness, in the context of National Institute
      of Health and Clinical Excellence (NICE) and Scottish Intercollegiate Guideline
      Network (SIGN) guidelines. It concludes that the evidence-based approaches allow
      intervention at different stages in the disease process of obesity, which are
      effective in different settings. Self-referral to commercial agencies, by
      individuals with relatively low body mass index (BMI) and few medical
      complications, is a reasonable first step. For more severely obese individuals
      (e.g. BMI > 35 kg m(-2) ) requiring more medically complicated care, evidence is
      largely lacking for these services, but the community-based Counterweight
      Programme is effective and cost-effective in maintaining weight loss >5 kg up to
      2 years for 30-40% of attenders. For more complicated and resistant obesity,
      referral to a secondary care-based service can generate short-term weight loss,
      but 12-month data are unavailable. 

PMID- 25586164
TI  - Clinical pictures.
AB  - A 6 year old girl presents with excessive weight gain. The clincal picture shown
      is a radiograph of the left hand and wrist. 

PMID- 25586165
TI  - Chronic ischaemia does not appear to hinder healing with Integra((r)) :
      implementation at a tibial artery bypass site.
AB  - Wounds with exposed vessels, especially in artery bypass procedures, can pose a
      barrier to adequate skin healing. Skin grafts or flaps are sometimes difficult to
      perform in the face of the ischaemia that is often present in such cases. We
      report a case of a 73-year-old man who presented with grade IV peripheral
      arterial disease necessitating salvage of the lower limb using artery bypass
      surgery. Immediate exposure of femorotibial artery secondary to skin necrosis
      following the bypass led us to propose an innovative means of wound coverage
      using Integra((r)) , a well-known dermal regeneration template. The wound healed
      uneventfully with an appearance similar to that of the adjacent skin.
      Integra((r)) seems to be less demanding in terms of the vascular wound bed and
      the degree of oxygenation than a conventional skin graft. This finding could
      support further indications for this dermal regeneration template. 

PMID- 25586166
TI  - Significance of apoptotic and non-apoptotic disseminated tumor cells in the bone
      marrow of patients with clinically localized prostate cancer.
AB  - BACKGROUND: Disseminated tumor cells (DTC) can be detected in a high proportion
      of patients with localized solid malignancies. In prostate cancer (PC),
      determination of DTCs is critically discussed as there are conflicting results on
      their prognostic value. The aim of the present study was to evaluate the presence
      and prognostic role of DTCs in PC patients with a high risk of disease
      recurrence. METHODS: 248 patients with clinically localized PC undergoing radical
      prostatectomy with features of increased risk of recurrence (PSA >=10 ng/ml or
      Gleason score >= 4 + 3 = 7 or pT >=3) were included. All patients underwent
      intraoperative bone marrow (BM) aspiration biopsy. BM cells were evaluated by
      immunocytochemistry for cytokeratines and the apoptosis marker caspase-cleaved
      cytokeratin 18 (M30). Results of immunocytochemistry were correlated with
      clinical and pathological parameters and clinical outcome of the patients.
      RESULTS: Of 248 patients, 47 (19.0%) had evidence of DTCs at time of radical
      prostatectomy. In 17 of these 47 patients (36.2%), DTCs expressed the apoptosis
      marker M30. We observed no correlation between the presence of DTCs and tumor
      stage, nodal stage, prostate-specific antigen, or Gleason score. After a median
      follow-up of 58 months (23-76), no differences in rates of biochemical
      recurrence, development of metastases and cancer-specific death were observed
      between patients with and without DTCs while apoptosis markers had no role.
      CONCLUSIONS: In a single-centre cohort of patients with increased risk for
      disease recurrence, the presence of DTCs at the time of prostatectomy does not
      influence clinical outcome. For the first time in patients with PC, DTCs were
      evaluated for immunocytological features indicating apoptosis. Due to conflicting
      results of studies on DTCs, BM biopsies at time of radical prostatectomy cannot
      be recommended as a standard procedure in patients with clinically localized PC.

PMID- 25586167
TI  - Anatomic shoulder replacement for primary osteoarthritis in patients over 80
      years: outcome is as good as in younger patients.
AB  - BACKGROUND AND PURPOSE: Anatomic total shoulder arthroplasty (TSA) gives good
      outcome in the treatment of primary osteoarthritis, but it is not known whether
      this also applies to patients over 80 years old. PATIENTS AND METHODS: We
      retrospectively assessed outcome in patients over the age of 80 after anatomic
      TSA, performed for primary osteoarthritis with a preoperative intact rotator cuff
      (group O, n = 32). We compared it with outcome in a group of patients under the
      age of 70 (group Y, n = 32). Subjective outcome, Constant score, and radiological
      findings were analyzed. RESULTS: At a mean follow-up time of 7 years, there were
      no statistically significant differences between the groups. In group O, 24
      patients were very satisfied and in group Y, 23 patients were very satisfied; the
      subjective shoulder value was 81% in both groups. Mean Constant score was 65 in
      group O and 67 in group Y. Moderate or severe radiological upper migration of the
      humeral head was detected in 1 patient in group O and in 3 patients in group Y.
      One patient in group Y was revised for glenoid loosening. INTERPRETATION: Good to
      excellent results can be expected after anatomic TSA in patients over the age of
      80. Our findings suggest that they have similar results to those in patients
      around 70 years of age.

PMID- 25586168
TI  - Echocardiographic predictors of survival in dogs with myxomatous mitral valve
      disease.
AB  - OBJECTIVES: To evaluate vena contracta and other echocardiographic measures of
      myxomatous mitral valve disease (MMVD) severity in a multivariable analysis of
      survival in dogs. ANIMALS: 70 dogs diagnosed with MMVD from stored
      echocardiographic images that met study inclusion criteria. METHODS: Left heart
      dimensions were measured as well as mitral regurgitant jet area/left atrial area
      (JAR), early mitral filling velocity (Evel), extent of mitral valve prolapse in
      right and left views (ProlR, ProlL), Prol indexed to aortic diameter (ProlR:Ao,
      ProlL:Ao), presence of a flail leaflet (FlailR, FlailL), and mitral regurgitation
      vena contracta diameter (VCR, VCL) indexed to aortic diameter (VCR:Ao, VCL:Ao).
      Follow-up from referring veterinarians was obtained by questionnaire or telephone
      to determine survival times. Inter- and intra-observer agreement was evaluated
      with Bland-Altman plots and weighted Kappa analysis. Survival was analyzed using
      Kaplan-Meier curves, logrank tests and Cox's proportional hazards. RESULTS:
      Logrank analysis showed VCL:Ao, VCR:Ao, FlailL, ProlR:Ao, ProlL:Ao, left
      ventricular internal dimension in diastole indexed to aortic diameter (LVIDD:Ao)
      >2.87, left atrium to aorta ratio (LA/Ao) >1.6, and Evel >1.4 m/s were predictors
      of cardiac mortality. In a multivariable analysis, the independent predictors of
      cardiac mortality were Evel >1.4 m/s [hazard ratio (HR) 5.0, 95% confidence
      interval (CI) 2.5-10.3], FlailL (HR 3.1, 95% CI 1.3-7.9), and ProlR:Ao (HR 2.8,
      95% CI 1.3-6.3). CONCLUSIONS: Echocardiographic measures of mitral regurgitation
      severity and mitral valve pathology provide valuable prognostic information
      independent of chamber enlargement in dogs with MMVD.

PMID- 25586169
TI  - Influence of dissolved oxygen conditions on toxicity of ammonium nitrate to
      larval natterjack toads.
AB  - Temporary ponds, where many amphibians from temperate regions breed, show an
      annual cycle with a maximum water volume in spring followed by a progressive
      desiccation throughout late spring and summer. This desiccation leads to a
      decrease in dissolved oxygen and an increase in nitrogen levels, which can
      additionally increase because of anthropogenic sources such as chemical
      fertilizers. We analyzed the toxicity posed by environmentally relevant levels of
      a common nitrogenous fertilizer, ammonium nitrate, at different conditions of
      oxygen availability to Bufo calamita tadpoles, which typically develop in
      ephemeral ponds. Ammonium nitrate (90.3 mg N-NO3NH4/l) and hypoxic conditions
      (initial dissolved oxygen 4.53 +/- 0.40 mg/l) caused significant lethal effects
      after 7 and 12 days of exposure, respectively. At the end of experiment (16
      days), mortality rates were 32.5 % in individuals exposed to the fertilizer and
      15 % in those growing under hypoxic conditions. When both stressors were
      combined, they showed an additive effect on tadpole survival. Malformations, such
      as oedemas and spinal curvatures, and locomotory abnormalities, were detected
      after 12 days of experiment in >90 % of individuals exposed to 45.2 mg N-NO3NH4/l
      under hypoxic conditions, whereas none of these stressors by separate related to
      abnormality rates >35 %. Delayed development was also observed in tadpoles
      exposed to ammonium nitrate with hypoxia affecting developmental rate only after
      12 days of exposure. The results are discussed in terms of potential mechanisms
      linking negative effects of both factors as well as in terms of potential
      alterations of the ecological plasticity that often allows amphibians to survive
      in unpredictable environments.

PMID- 25586170
TI  - Appropriate use of information in therapeutic decision-making: reflections on
      indirect comparisons.
AB  - Although the statistical strength of direct comparative randomized controlled
      trials is generally acknowledged, the particular demands of therapeutic decision
      making will often require indirect comparisons to be made, based on pooled data
      from multiple trials. As for all post-hoc analyses, the process of indirect
      comparison runs the risk of introducing significant bias into the results and
      consequently a robust statistical approach is required, in order to minimise the
      risk. To address this problem, a range of different methodologies have been
      developed over the past twenty years, using both frequentist and Bayesian models.
      It is important to appreciate the strengths and limitations of these techniques:
      however, the technical complexities tend to make this type of analysis somewhat
      opaque to the non-specialist reader. In this article, we consider the use of a
      simple, non-specialist critical appraisal tool developed by ISPOR, which allows
      methodological and interpretive errors to be identified and flagged as potential
      sources of bias, even when the detailed statistical methodology is not well
      understood by the reader.

PMID- 25586171
TI  - Hepatitis C virus treatment as prevention among injecting drug users: who should
      we cure first?
AB  - BACKGROUND AND AIMS: Treatment of injecting drug users (IDU) for hepatitis C
      virus (HCV) infection may prevent onward transmission. Treating individuals who
      often share injecting equipment is most likely to prevent new infections.
      However, these high-risk IDU are also more likely to become re-infected than low
      risk IDU. We investigated to which group treatment is best targeted. DESIGN: We
      modelled the expected benefits per treatment of one chronically HCV-infected IDU
      in a population of low- and high-risk IDU. The benefits of treating one low- or
      one high-risk IDU were compared. MEASUREMENTS: Benefits included the probability
      for the treated IDU to become and remain uninfected, as well as the expected
      number of prevented infections to others (i.e. we quantified the total expected
      decrease in chronic infections). FINDINGS: We found a threshold in HCV-RNA
      prevalence above which treating low-risk IDU, and below which treating high-risk
      IDU, resulted in the greatest benefits. This threshold was at 50% of exchanged
      syringes being HCV contaminated. When 42% of IDU engaged in high-risk behaviour
      (borrowing and lending out syringes 7.3 times more frequently than low-risk IDU),
      the corresponding threshold of HCV-RNA prevalence among IDU was at 32%. Larger
      risk heterogeneity led to a lower corresponding threshold among IDU. A
      combination of HCV treatment and 50% risk reduction was best directed at high
      risk IDU for prevalence among syringes up to 59%. The threshold was marginally
      sensitive to changes in disease and treatment variables. CONCLUSIONS: When more
      than half of all exchanged syringes in a population of injecting drug users (IDU)
      are contaminated by hepatitis C virus, it is most efficient to treat low-risk IDU
      first. Below this threshold, it is most efficient to treat high-risk IDU first.

PMID- 25586172
TI  - Retinal nerve fibre layer thickness measured with SD-OCT in a population-based
      study of French elderly subjects: the Alienor study.
AB  - PURPOSE: To establish normative data of retinal nerve fibre layer (RNFL)
      thickness in the elderly and to determine the factors influencing its thickness.
      METHODS: Peripapillary RNFL thickness was measured with spectral domain OCT (SD
      OCT) in 210 elderly participants from the Alienor population-based study who were
      aged 75 years or older. The measure was assessed in six segments (the
      superotemporal, temporal, inferotemporal, inferonasal, nasal and superonasal
      segments). RNFL data were analysed across age and sex strata in non-glaucoma
      participants. Mixed linear models were used to evaluate the associations of RNFL
      thickness with age, sex, ocular parameters and vascular risk factors. RESULTS:
      The mean global RNFL thickness was 91.4 MUm (SD: 12.6), ranging from 55 to 122;
      the highest values were found in the inferotemporal and superotemporal segments.
      After adjustment for sex and ocular parameters, including axial length,
      increasing age was significantly associated with lower thickness globally (mean
      thinning per decade = 5.6 MUm, p = 0.003), in the superotemporal (-12.7 MUm per
      decade, p < 0.0001) and inferotemporal (-8.1 MUm per decade, p = 0.022) segments.
      RNFL thickness tended to be higher in women than in men, but this trend was
      significant only in the inferotemporal segment (+6.6 MUm for women, p = 0.012).
      The axial length was associated with RNFL thickness globally and in most
      segments. RNFL thickness did not differ according to cataract extraction. There
      were no associations between vascular factors and RNFL thickness. CONCLUSION:
      Retinal nerve fibre layer thickness decreased with age globally and in the supero
      and inferotemporal segments, even after 75 years; it also tended to be higher in
      women, particularly in the inferotemporal segment. Normative data on RNFL
      thickness should consider these characteristics as well as ocular parameters,
      particularly axial length.

PMID- 25586173
TI  - Conserved movement of TMS11 between occluded conformations of LacY and XylE of
      the major facilitator superfamily suggests a similar hinge-like mechanism.
AB  - The Delta-distance maps can detect local remodeling that is difficult to
      accurately determine using superimpositions. Transmembrane segments (TMSs) 11 in
      both LacY and XylE of the major facilitator superfamily uniquely contribute the
      greatest amount of mobile surface area in the outward-occluded state and undergo
      analogous movements. The intracellular part of TMS11 moves away from the C
      terminal domain and into the substrate cavity during the conformational change
      from the outward-occluded to the inward-occluded state. A difference was noted
      between LacY and XylE when they assumed the inward open state after releasing a
      substrate to the inside in which TMS11 of LacY moved further into the substrate
      release space, whereas in XylE, TMS11 slightly retracted into the C-terminal
      domain. Independent movement of the N-terminal half of TMS11 suggests that it is
      flexible in the middle. Repeat-swapped homology modeling was used to discover
      that a loop connecting TMSs 10 and 11 in LacY probably moves during the
      transition between the unavailable outward-open state and the outward-occluded
      state. TMSs 11 and the other elements displaying a notable domain-independent
      movement colocalize with the interdomain linker, suggesting that these elements
      could drive the alternating access movement between the domain halves.
      Preliminary evidence indicates that analogous movements occur in other members of
      the major facilitator superfamily.

PMID- 25586175
TI  - Overexpression of isocitrate dehydrogenase-1R132H enhances the proliferation of
      A172 glioma cells via aerobic glycolysis.
AB  - Gliomas are the most common type of primary malignancy of the central nervous
      system. The identification of mutations in the gene encoding isocitrate
      dehydrogenase-1 (IDH1) represents a key area of investigation in studies on
      glioma. The IDH1R132H mutation is a heterozygous point mutation, which affects
      the amino acid arginine at position 132, however, the metabolic importance of
      this mutation in tumor cell growth remains to be elucidated. In the present
      study, A172 glioma cell lines stably overexpressing either wild-type IDH1 or
      IDH1R132H were produced. The results demonstrated that the IDH1R132H mutation
      enhanced the proliferation of the A172 glioma cells in vitro. Furthermore,
      IDH1R132H performed this function by elevating the expression levels of hypoxia
      inducible factor-1alpha, leading to an increase in the expression levels of the
      key glycolytic enzymes, glucose transporter 1 and hexokinase 2. Therefore, the
      metabolism was shifted towards aerobic glycolysis, leading to an increase in
      glucose uptake and lactate production. These findings demonstrated that the
      IDH1R132H molecular target was involved in orchestrating the Warburg effect in
      mutant IDH1R132H glioma cells.

PMID- 25586174
TI  - Glucose modulation induces reactive oxygen species and increases P-glycoprotein
      mediated multidrug resistance to chemotherapeutics.
AB  - BACKGROUND AND PURPOSE: Cancer cells develop resistance to stress induced by
      chemotherapy. In tumours, a considerable glucose gradient exists, resulting in
      stress. Notably, hypoxia-inducible factor-1 (HIF-1) is a redox-sensitive
      transcription factor that regulates P-glycoprotein (Pgp), a crucial drug-efflux
      transporter involved in multidrug resistance (MDR). Here, we investigated how
      glucose levels regulate Pgp-mediated drug transport and resistance. EXPERIMENTAL
      APPROACH: Human tumour cells (KB31, KBV1, A549 and DMS-53) were incubated under
      glucose starvation to hyperglycaemic conditions. Flow cytometry assessed reactive
      oxygen species (ROS) generation and Pgp activity. HIF-1alpha, NF-kappaB and Pgp
      expression were assessed by reverse transcriptase-PCR and Western blotting.
      Fluorescence microscopy examined p65 distribution and a luciferase-reporter assay
      assessed HIF-1 promoter-binding activity. The effect of glucose-induced stress on
      Pgp-mediated drug resistance was examined after incubating cells with the
      chemotherapeutic and Pgp substrate, doxorubicin (DOX), and performing MTT assays
      validated by viable cell counts. KEY RESULTS: Changes in glucose levels markedly
      enhanced cellular ROS and conferred Pgp-mediated drug resistance. Low and high
      glucose levels increased (i) ROS generation via NADPH oxidase 4 and mitochondrial
      membrane destabilization; (ii) HIF-1 activity; (iii) nuclear translocation of the
      NF-kappaB p65 subunit; and (iv) HIF-1alpha mRNA and protein levels. Increased HIF
      1alpha could also be due to decreased prolyl hydroxylase protein under these
      conditions. The HIF-1alpha target, Pgp, was up-regulated at low and high glucose
      levels, which led to lower cellular accumulation of Pgp substrate, rhodamine123,
      and greater resistance to DOX. CONCLUSIONS AND IMPLICATIONS: As tumour cells
      become glucose-deprived or exposed to high glucose levels, this increases stress,
      leading to a more aggressive MDR phenotype via up-regulation of Pgp.

PMID- 25586176
TI  - Tumor necrosis factor (TNF)-alpha-induced repression of GKAP42 protein levels
      through cGMP-dependent kinase (cGK)-Ialpha causes insulin resistance in 3T3-L1
      adipocytes.
AB  - Insulin receptor substrates (IRSs) have been shown to be major mediators of
      insulin signaling. Recently, we found that IRSs form high-molecular weight
      complexes, and here, we identify by yeast two-hybrid screening a novel IRS-1
      associated protein: a 42-kDa cGMP-dependent protein kinase-anchoring protein
      (GKAP42). GKAP42 knockdown in 3T3-L1 adipocytes suppressed insulin-dependent IRS
      1 tyrosine phosphorylation and downstream signaling, resulting in suppression of
      GLUT4 translocation to plasma membrane induced by insulin. In addition, GLUT4
      translocation was also suppressed in cells overexpressing GKAP42-N (the IRS-1
      binding region of GKAP42), which competed with GKAP42 for IRS-1, indicating that
      GKAP42 binding to IRS-1 is required for insulin-induced GLUT4 translocation. Long
      term treatment of 3T3-L1 adipocytes with TNF-alpha, which induced insulin
      resistance, significantly decreased the GKAP42 protein level. We then
      investigated the roles of cGMP-dependent kinase (cGK)-Ialpha, which bound to
      GKAP42, in these changes. cGK-Ialpha knockdown partially rescued TNF-alpha
      induced decrease in GKAP42 and impairment of insulin signals. These data
      indicated that TNF-alpha-induced repression of GKAP42 via cGK-Ialpha caused
      reduction of insulin-induced IRS-1 tyrosine phosphorylation at least in part. The
      present study describes analysis of the novel TNF-alpha-induced pathway, cGK
      Ialpha-GKAP42, which regulates insulin-dependent signals and GLUT4 translocation.

PMID- 25586177
TI  - Short term exposure of beta cells to low concentrations of interleukin-1beta
      improves insulin secretion through focal adhesion and actin remodeling and
      regulation of gene expression.
AB  - Type 2 diabetes involves defective insulin secretion with islet inflammation
      governed in part by IL-1beta. Prolonged exposure of islets to high concentrations
      of IL-1beta (>24 h, 20 ng/ml) impairs beta cell function and survival.
      Conversely, exposure to lower concentrations of IL-1beta for >24 h improves these
      same parameters. The impact on insulin secretion of shorter exposure times to IL
      1beta and the underlying molecular mechanisms are poorly understood and were the
      focus of this study. Treatment of rat primary beta cells, as well as rat or human
      whole islets, with 0.1 ng/ml IL-1beta for 2 h increased glucose-stimulated (but
      not basal) insulin secretion, whereas 20 ng/ml was without effect. Similar
      differential effects of IL-1beta depending on concentration were observed after
      15 min of KCl stimulation but were prevented by diazoxide. Studies on sorted rat
      beta cells indicated that the enhancement of stimulated secretion by 0.1 ng/ml IL
      1beta was mediated by the NF-kappaB pathway and c-JUN/JNK pathway acting in
      parallel to elicit focal adhesion remodeling and the phosphorylation of paxillin
      independently of upstream regulation by focal adhesion kinase. Because the
      beneficial effect of IL-1beta was dependent in part upon transcription, gene
      expression was analyzed by RNAseq. There were 18 genes regulated uniquely by 0.1
      but not 20 ng/ml IL-1beta, which are mostly involved in transcription and
      apoptosis. These results indicate that 2 h of exposure of beta cells to a low but
      not a high concentration of IL-1beta enhances glucose-stimulated insulin
      secretion through focal adhesion and actin remodeling, as well as modulation of
      gene expression. 

PMID- 25586178
TI  - The extracellular A-loop of dual oxidases affects the specificity of reactive
      oxygen species release.
AB  - NADPH oxidase (Nox) family proteins produce superoxide (O2 (?)) directly by
      transferring an electron to molecular oxygen. Dual oxidases (Duoxes) also produce
      an O2 (?) intermediate, although the final species secreted by mature Duoxes is
      H2O2, suggesting that intramolecular O2 (?) dismutation or other mechanisms
      contribute to H2O2 release. We explored the structural determinants affecting
      reactive oxygen species formation by Duox enzymes. Duox2 showed O2 (?) leakage
      when mismatched with Duox activator 1 (DuoxA1). Duox2 released O2 (?) even in
      correctly matched combinations, including Duox2 + DuoxA2 and Duox2 + N-terminally
      tagged DuoxA2 regardless of the type or number of tags. Conversely, Duox1 did not
      release O2 (?) in any combination. Chimeric Duox2 possessing the A-loop of Duox1
      showed no O2 (?) leakage; chimeric Duox1 possessing the A-loop of Duox2 released
      O2 (?). Moreover, Duox2 proteins possessing the A-loops of Nox1 or Nox5 co
      expressed with DuoxA2 showed enhanced O2 (?) release, and Duox1 proteins
      possessing the A-loops of Nox1 or Nox5 co-expressed with DuoxA1 acquired O2 (?)
      leakage. Although we identified Duox1 A-loop residues (His(1071), His(1072), and
      Gly(1074)) important for reducing O2 (?) release, mutations of these residues to
      those of Duox2 failed to convert Duox1 to an O2 (?)-releasing enzyme. Using
      immunoprecipitation and endoglycosidase H sensitivity assays, we found that the A
      loop of Duoxes binds to DuoxA N termini, creating more stable, mature Duox-DuoxA
      complexes. In conclusion, the A-loops of both Duoxes support H2O2 production
      through interaction with corresponding activators, but complex formation between
      the Duox1 A-loop and DuoxA1 results in tighter control of H2O2 release by the
      enzyme complex. 

PMID- 25586179
TI  - Biophysical measurement of the balance of influenza a hemagglutinin and
      neuraminidase activities.
AB  - The interaction of influenza A viruses with the cell surface is controlled by the
      surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). These two
      glycoproteins have opposing activities: HA is responsible for binding the host
      receptor (sialic acid) to allow infection, and NA is responsible for cleaving the
      receptor to facilitate virus release. Several studies have demonstrated that
      compatible levels of HA and NA activity are required for a virus to replicate
      efficiently. This is consequently of great interest for determining virus
      transmissibility. The concurrent role of these two proteins in receptor binding
      has never been directly measured. We demonstrate a novel biophysical approach
      based on bio-layer interferometry to measure the balance of the activities of
      these two proteins in real time. This technique measures virus binding to and
      release from a surface coated with either the human-like receptor analog alpha2,6
      linked sialic acid or the avian-like receptor analog alpha2,3-linked sialic acid
      in both the presence and absence of NA inhibitors. Bio-layer interferometry
      measurements were also carried out to determine the effect of altering HA
      receptor affinity and NA stalk length on receptor binding. 

PMID- 25586180
TI  - Functional amyloids keep quorum-sensing molecules in check.
AB  - The mechanism by which extracellular metabolites, including redox mediators and
      quorum-sensing signaling molecules, traffic through the extracellular matrix of
      biofilms is poorly explored. We hypothesize that functional amyloids, abundant in
      natural biofilms and possessing hydrophobic domains, retain these metabolites.
      Using surface plasmon resonance, we demonstrate that the quorum-sensing (QS)
      molecules, 2-heptyl-3-hydroxy-4(1H)-quinolone and N-(3-oxododecanoyl)-l
      homoserine lactone, and the redox mediator pyocyanin bind with transient affinity
      to functional amyloids from Pseudomonas (Fap). Their high hydrophobicity
      predisposes them to signal-amyloid interactions, but specific interactions also
      play a role. Transient interactions allow for rapid association and dissociation
      kinetics, which make the QS molecules bioavailable and at the same time secure
      within the extracellular matrix as a consequence of serial bindings. Retention of
      the QS molecules was confirmed using Pseudomonas aeruginosa PAO1-based 2-heptyl-3
      hydroxy-4(1H)-quinolone and N-(3-oxododecanoyl)-l-homoserine lactone reporter
      assays, showing that Fap fibrils pretreated with the QS molecules activate the
      reporters even after sequential washes. Pyocyanin retention was validated by
      electrochemical analysis of pyocyanin-pretreated Fap fibrils subjected to the
      same washing process. Results suggest that QS molecule-amyloid interactions are
      probably important in the turbulent environments commonly encountered in natural
      habitats. 

PMID- 25586181
TI  - UBC9-dependent association between calnexin and protein tyrosine phosphatase 1B
      (PTP1B) at the endoplasmic reticulum.
AB  - Calnexin is a type I integral endoplasmic reticulum (ER) membrane protein,
      molecular chaperone, and a component of the translocon. We discovered a novel
      interaction between the calnexin cytoplasmic domain and UBC9, a SUMOylation E2
      ligase, which modified the calnexin cytoplasmic domain by the addition of SUMO.
      We demonstrated that calnexin interaction with the SUMOylation machinery
      modulates an interaction with protein tyrosine phosphatase 1B (PTP1B), an ER
      associated protein tyrosine phosphatase involved in the negative regulation of
      insulin and leptin signaling. We showed that calnexin and PTP1B form UBC9
      dependent complexes, revealing a previously unrecognized contribution of calnexin
      to the retention of PTP1B at the ER membrane. This work shows that the
      SUMOylation machinery links two ER proteins from divergent pathways to
      potentially affect cellular protein quality control and energy metabolism. 

PMID- 25586182
TI  - The bipartite rac1 Guanine nucleotide exchange factor engulfment and cell
      motility 1/dedicator of cytokinesis 180 (elmo1/dock180) protects endothelial
      cells from apoptosis in blood vessel development.
AB  - Engulfment and cell motility 1/dedicator of cytokinesis 180 (Elmo1/Dock180) is a
      bipartite guanine nucleotide exchange factor for the monomeric GTPase Ras-related
      C3 botulinum toxin substrate 1 (Rac1). Elmo1/Dock180 regulates Rac1 activity in a
      specific spatiotemporal manner in endothelial cells (ECs) during zebrafish
      development and acts downstream of the Netrin-1/Unc5-homolog B (Unc5B) signaling
      cascade. However, mechanistic details on the pathways by which Elmo1/Dock180
      regulates endothelial function and vascular development remained elusive. In this
      study, we aimed to analyze the vascular function of Elmo1 and Dock180 in human
      ECs and during vascular development in zebrafish embryos. In vitro overexpression
      of Elmo1 and Dock180 in ECs reduced caspase-3/7 activity and annexin V-positive
      cell number upon induction of apoptosis. This protective effect of Elmo1 and
      Dock180 is mediated by activation of Rac1, p21-activated kinase (PAK) and
      AKT/protein kinase B (AKT) signaling. In zebrafish, Elmo1 and Dock180
      overexpression reduced the total apoptotic cell and apoptotic EC number and
      promoted the formation of blood vessels during embryogenesis. In conclusion,
      Elmo1 and Dock180 protect ECs from apoptosis by the activation of the
      Rac1/PAK/AKT signaling cascade in vitro and in vivo. Thus, Elmo1 and Dock180
      facilitate blood vessel formation by stabilization of the endothelium during
      angiogenesis. 

PMID- 25586183
TI  - 15-Hydroxyprostaglandin dehydrogenase generation of electrophilic lipid signaling
      mediators from hydroxy omega-3 fatty acids.
AB  - 15-Hydroxyprostaglandin dehydrogenase (15PGDH) is the primary enzyme catalyzing
      the conversion of hydroxylated arachidonic acid species to their corresponding
      oxidized metabolites. The oxidation of hydroxylated fatty acids, such as the
      conversion of prostaglandin (PG) E2 to 15-ketoPGE2, by 15PGDH is viewed to
      inactivate signaling responses. In contrast, the typically electrophilic products
      can also induce anti-inflammatory and anti-proliferative responses. This study
      determined that hydroxylated docosahexaenoic acid metabolites (HDoHEs) are
      substrates for 15PGDH. Examination of 15PGDH substrate specificity was conducted
      in cell culture (A549 and primary human airway epithelia and alveolar
      macrophages) using chemical inhibition and shRNA knockdown of 15PGDH. Substrate
      specificity is broad and relies on the carbon position of the acyl chain hydroxyl
      group. 14-HDoHE was determined to be the optimal DHA substrate for 15PGDH,
      resulting in the formation of its electrophilic metabolite, 14-oxoDHA. Consistent
      with this, 14-HDoHE was detected in bronchoalveolar lavage cells of mild to
      moderate asthmatics, and the exogenous addition of 14-oxoDHA to primary alveolar
      macrophages inhibited LPS-induced proinflammatory cytokine mRNA expression. These
      data reveal that 15PGDH-derived DHA metabolites are biologically active and can
      contribute to the salutary signaling actions of Omega-3 fatty acids. 

PMID- 25586184
TI  - Cellular asymmetric catalysis by UDP-glucuronosyltransferase 1A8 shows functional
      localization to the basolateral plasma membrane.
AB  - UDP-glucuronosyltransferases (UGTs) are highly expressed in liver, intestine and
      kidney, and catalyze the glucuronic acid conjugation of both endogenous compounds
      and xenobiotics. Using recombinant human UGT isoforms, we show that glucuronic
      acid conjugation of the model substrate, (-)-epicatechin, is catalyzed mainly by
      UGT1A8 and UGT1A9. In HepG2 cells, pretreatment with polyunsaturated fatty acids
      increased substrate glucuronidation. In the intestinal Caco-2/HT29-MTX co-culture
      model, overall relative glucuronidation rates were much higher than in HepG2
      cells, and (-)-epicatechin was much more readily conjugated when applied to the
      basolateral side of the cell monolayer. Under these conditions, 95% of the
      conjugated product was effluxed back to the site of application, and none of the
      other phase 2-derived metabolites followed this distribution pattern. HT29-MTX
      cells contained >1000-fold higher levels of UGT1A8 mRNA than Caco-2 or HepG2
      cells. Gene expression of UGT1A8 increased after treatment of cells with
      docosahexaenoic acid, as did UGT1A protein levels. Immunofluorescence staining
      and Western blotting showed the presence of UGT1A in the basal and lateral parts
      of the plasma membrane of HT29-MTX cells. These results suggest that some of the
      UGT1A8 enzyme is not residing in the endoplasmic reticulum but spans the plasma
      membrane, resulting in increased accessibility to compounds outside the cell.
      This facilitates more efficient conjugation of substrate and is additionally
      coupled with rapid efflux by functionally associated basolateral transporters.
      This novel molecular strategy allows the cell to carry out conjugation without
      the xenobiotic entering into the interior of the cell. 

PMID- 25586185
TI  - Highly amyloidogenic two-chain peptide fragments are released upon partial
      digestion of insulin with pepsin.
AB  - Proteases play a well recognized role in the emergence of highly aggregation
      prone protein fragments in vivo, whereas in vitro limited proteolysis is often
      employed to probe different phases of amyloidogenic pathways. Here, we show that
      addition of moderate amounts of pepsin to acidified bovine insulin at close to
      physiological temperature results in an abrupt self-assembly of amyloid-like
      fibrils from partially digested insulin fragments. Biochemical analysis of the
      pepsin-induced fibrils implicates peptide fragments (named H) consisting of the
      13 or 15 N-terminal residues of the A-chain and 11 or 13 N-terminal residues of
      the B-chain linked by the disulfide bond between Cys-7A-Cys-7B as the main
      constituents. There are up to eight pepsin-cleavage sites remaining within the
      double chain peptide, which become protected upon fast fibrillation unless
      concentration of the enzyme is increased resulting in complete digestion of
      insulin. Controlled re-association of H-peptides leads to "explosive"
      fibrillation only under nonreducing conditions implying the key role of the
      disulfide bond in their amyloidogenicity. Such re-assembled amyloid is similar in
      terms of morphology and infrared features to typical bovine insulin fibrils,
      although it lacks the ability to seed the intact protein. 

PMID- 25586186
TI  - Scaffold protein JLP is critical for CD40 signaling in B lymphocytes.
AB  - CD40 expression on the surface of B lymphocytes is essential for their biological
      function and fate decision. The engagement of CD40 with its cognate ligand,
      CD154, leads to a sequence of cellular events in B lymphocytes, including CD40
      cytoplasmic translocation, a temporal and spatial organization of effector
      molecules, and a cascade of CD40-induced signal transduction. The JLP scaffold
      protein was expressed in murine B lymphocytes. Using B lymphocytes from jlp
      deficient mice, we observed that JLP deficiency resulted in defective CD40
      internalization upon CD154/CD40 engagement. Examination of interactions and co
      localization among CD40, JLP, dynein, and Rab5 in B lymphocytes suggested that
      CD40 internalization is a process of JLP-mediated vesicle transportation that
      depends on Rab5 and dynein. JLP deficiency also diminished CD40-dependent
      activation of MAPK and JNK, but not NF-kappaB. Inhibiting vesicle transportation
      from the direction of cell periphery to the cell center by a dynein inhibitor
      (ciliobrevin D) impaired both CD154-induced CD40 internalization and CD40
      dependent MAPK activities in B lymphocytes. Collectively, our data demonstrate a
      novel role of the JLP scaffold protein in the bridging of CD154-triggered CD40
      internalization and CD40-dependent signaling in splenic B lymphocytes. 

PMID- 25586187
TI  - Alteration of lysosome fusion and low-grade inflammation mediated by super-low
      dose endotoxin.
AB  - Subclinical super-low-dose endotoxin LPS is a risk factor for the establishment
      of low-grade inflammation during the pathogenesis and progression of chronic
      diseases. However, the underlying mechanisms are not well understood. At the
      cellular level, a disruption of lysosome fusion with endosomes or autophagosomes
      may contribute to the potentiation of low-grade inflammation. In this study, we
      identified that subclinical super-low-dose endotoxin LPS can potently inhibit the
      process of endosome acidification and lysosome fusion with endosomes or
      autophagosomes in primary macrophages. Super-low-dose LPS induced the inhibitory
      phosphorylation of VPS34, thus leading to the disruption of endosome-lysosome
      fusion. This effect may depend upon the clearance and relocation of Tollip in
      macrophages by super-low-dose LPS. Consistent with this notion, Tollip-deficient
      macrophages had constitutively elevated levels of VPS34 inhibitory
      phosphorylation and constitutive disruption of endosome-lysosome fusion. By
      employing a skin excision wound-healing model, we observed that Tollip-deficient
      mice had significantly elevated levels of cell stress and reduced wound repair.
      This study reveals a novel mechanism responsible for the modulation of endosome
      lysosome fusion and low-grade inflammation in innate macrophages. 

PMID- 25586188
TI  - The N-Glycan cluster from Xanthomonas campestris pv. campestris: a toolbox for
      sequential plant N-glycan processing.
AB  - N-Glycans are widely distributed in living organisms but represent only a small
      fraction of the carbohydrates found in plants. This probably explains why they
      have not previously been considered as substrates exploited by phytopathogenic
      bacteria during plant infection. Xanthomonas campestris pv. campestris, the
      causal agent of black rot disease of Brassica plants, possesses a specific system
      for GlcNAc utilization expressed during host plant infection. This system
      encompasses a cluster of eight genes (nixE to nixL) encoding glycoside hydrolases
      (GHs). In this paper, we have characterized the enzymatic activities of these GHs
      and demonstrated their involvement in sequential degradation of a plant N-glycan
      using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and
      one xylose (N2M3FX) as a substrate. The removal of the alpha-1,3-mannose by the
      alpha-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the
      beta-xylosidase NixI (GH3), which is involved in the cleavage of the beta-1,2
      xylose, followed by the alpha-mannosidase NixJ (GH125), which removes the alpha
      1,6-mannose. These data, combined to the subcellular localization of the enzymes,
      allowed us to propose a model of N-glycopeptide processing by X. campestris pv.
      campestris. This study constitutes the first evidence suggesting N-glycan
      degradation by a plant pathogen, a feature shared with human pathogenic bacteria.
      Plant N-glycans should therefore be included in the repertoire of molecules
      putatively metabolized by phytopathogenic bacteria during their life cycle. 

PMID- 25586189
TI  - SH2B1 and IRSp53 proteins promote the formation of dendrites and dendritic
      branches.
AB  - SH2B1 is an adaptor protein known to enhance neurite outgrowth. In this study, we
      provide evidence suggesting that the SH2B1 level is increased during in vitro
      culture of hippocampal neurons, and the beta isoform (SH2B1beta) is the
      predominant isoform. The fact that formation of filopodia is prerequisite for
      neurite initiation suggests that SH2B1 may regulate filopodium formation and thus
      neurite initiation. To investigate whether SH2B1 may regulate filopodium
      formation, the effect of SH2B1 and a membrane and actin regulator, IRSp53
      (insulin receptor tyrosine kinase substrate p53), is investigated. Overexpressing
      both SH2B1beta and IRSp53 significantly enhances filopodium formation, neurite
      outgrowth, and branching. Both in vivo and in vitro data show that SH2B1
      interacts with IRSp53 in hippocampal neurons. This interaction depends on the N
      terminal proline-rich domains of SH2B1. In addition, SH2B1 and IRSp53 co-localize
      at the plasma membrane, and their levels increase in the Triton X-100-insoluble
      fraction of developing neurons. These findings suggest that SH2B1-IRSp53
      complexes promote the formation of filopodia, neurite initiation, and neuronal
      branching. 

PMID- 25586190
TI  - Licochalcone A induces apoptosis in malignant pleural mesothelioma through
      downregulation of Sp1 and subsequent activation of mitochondria-related apoptotic
      pathway.
AB  - Licochalcone A (LCA) is a natural product derived from the roots of Glycyrrhiza
      inflata exhibiting a wide range of bioactivities such as antitumor, anti-oxidant
      and anti-bacterial effects. Malignant pleural mesothelioma (MPM) is an extremely
      aggressive type of cancer with a poor prognosis because of its rapid progression.
      However, LCA has not been investigated concerning its effects on MPM.
      Preliminarily, we observed that LCA negatively modulated not only cell growth,
      but also specificity protein 1 (Sp1) expression in MSTO-211H and H28 cell lines.
      It was found that IC50 values of LCA for growth inhibition of MSTO-211H and H28
      cells were approximately 26 and 30 uM, respectively. Consistent with
      downregulation of Sp1, expression of Sp1 regulatory proteins such as Cyclin D1,
      Mcl-1 and Survivin was substantially diminished. Mechanistically, LCA triggered
      the mitochondrial apoptotic pathway by affecting the ratio of mitochondrial
      proapoptotic Bax to anti-apoptotic Bcl-xL. Bid induced loss of mitochondrial
      membrane potential, eventually leading to multi-caspase activation and increased
      sub-G1 population. Moreover, nuclear staining with DAPI highlighted nuclear
      condensation and fragmentation of apoptotic features. Flow cytometry analyses
      after staining cells with Annexin V and propiodium iodide corroborated LCA
      mediated apoptotic cell death of MPM cells. In conclusion, these results present
      that LCA may be a potential bioactive material to control human MPM cells by
      apoptosis via the downregulation of Sp1.

PMID- 25586192
TI  - A systematic review of ketamine for complex regional pain syndrome.
AB  - OBJECTIVE: This systematic review aims to examine the available literature and to
      synthesize published data concerning the treatment of Complex Regional Pain
      Syndrome (CRPS) with ketamine. METHODS: The search was conducted utilizing the
      databases Medline, Embase and the Cochrane Central Registry of Controlled Trials.
      All relevant articles were systematically reviewed. RESULTS: The search yielded
      262 articles, 45 of which met the inclusion/exclusion criteria. Of those
      included, 6 were reviews, 5 were randomized placebo-controlled trials, 13 were
      observational studies, and 21 were case reports. CONCLUSION: There is no high
      quality evidence available evaluating the efficacy of ketamine for CRPS and all
      manuscripts examined in this review were of moderate to low quality. Therefore,
      we conclude there is currently only weak evidence supporting the efficacy of
      ketamine for CRPS, yet there is clearly a rationale for definitive study.

PMID- 25586191
TI  - CHST11 gene expression and DNA methylation in breast cancer.
AB  - Our previously published data link P-selectin-reactive chondroitin sulfate
      structures on the surface of breast cancer cells to metastatic behavior of cells.
      We have shown that a particular sulfation pattern mediated by the expression of
      carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) correlates with P
      selectin binding and aggressiveness of human breast cancer cell lines. The
      present study was performed to evaluate the prognostic value of CHST11 expression
      and determine whether aberrant DNA methylation controls CHST11 expression in
      breast cancer. Publicly available datasets were used to examine the association
      of CHST11 expression to aggressiveness and progression of breast cancer.
      Methylation status was analyzed using bisulfite genomic sequencing. 5-aza-2'
      deoxycytidine (5AzadC) was used for DNA demethylation. Reduced representation
      bisulfite sequencing was performed in the CpG island of CHST11 with a minimum
      coverage of 10. Quantitative real-time RT-PCR was employed to confirm the
      expression profile of CHST11 in breast cancer cell lines. Flow cytometry was also
      used to confirm the expression of the CHST11 product, chondroitin sulfate A (CS
      A). The expression of CHST11 was significantly higher in basal-like and Her2
      amplified cell lines compared to luminal cell lines. CHST11 was also highly
      expressed in cancer tissues compared to normal tissues and the expression levels
      were significantly associated with tumor progression. We observed very low levels
      of DNA methylation in a CpG island of CHST11 in basal-like cells but very high
      levels in the same region in luminal cells. Treatment of MCF7 cells, a luminal
      cell line with very low expression of CHST11, with 5AzadC increased the
      expression of CHST11 and its immediate product, CS-A, in a dose-dependent manner.
      These results suggest that CHST11 may play a direct role in progression of breast
      cancer and that its expression is controlled by DNA methylation. Therefore, in
      addition to CHST11 mRNA levels, the methylation status of this gene also has
      potential as a prognostic biomarker.

PMID- 25586193
TI  - Oxidative stress and histopathological alterations in liver of Cyprinus carpio L.
      induced by intraperitoneal injection of microcystin-LR.
AB  - Microcystins (MCs) are a group of cyclic heptapeptide hepatotoxic peptides
      produced by cyanobacteria. Microcystins-LR (MC-LR) can inhibit the activities of
      protein phosphatase type 1 and type 2A (PP1 and PP2A) and induce excessive
      production of reactive oxygen species (ROS). However, the detailed toxicological
      mechanism involving oxidative stress in carp (Cyprinus carpio L.) remains largely
      unclear. In our present study, the effects of sublethal intraperitoneal doses of
      MC-LR on the oxidative stress and pathological changes in carp liver were
      investigated. No significant changes of xanthine oxidase were observed,
      suggesting it might not contribute to over-production of ROS in the liver of fish
      during 48 h exposure to sublethal intraperitoneal doses of MC-LR. Superoxide
      dismutase activity in the 50 MUg kg(-1) group was significantly induced at 1-24
      h. The strongest inhibition of the catalase activity was shown at 48 h after 120
      MUg kg(-1) MC-LR exposure, with an inhibition rate of 33.7% compared to the
      control group. In general, a significant depletion of intracellular reduced
      glutathione was found at 5-12 h after 50 and 120 MUg kg(-1) MC-LR exposure, which
      was mainly due to the conjugation reaction to MC-LR catalyzed by glutathione-S
      transferase and its subsequent excretion. Oxidative damages induced by MC-LR were
      evidenced by the significant elevation in malondialdehyde levels. In addition, a
      series of histopathological alterations in fish livers were observed, and the
      most severe hepatic injuries were found at 5-12 h, which could contribute to the
      efflux of intracellular GSH. Our study further supports the important role of
      oxidative stress involved in MC-LR induced liver injury in aquatic organisms.

PMID- 25586194
TI  - The cytoprotective effects of endogenous activated protein C reduce activation of
      coagulation during murine pneumococcal pneumonia and sepsis.
AB  - INTRODUCTION: Streptococcus (S.) pneumoniae is the most common causative pathogen
      in community-acquired pneumonia and sepsis. Activated protein C (APC) has been
      implicated as an important anticoagulant and anti-inflammatory mediator. We here
      sought to determine the role of the anticoagulant and cytoprotective functions of
      endogenous APC during pneumonia and sepsis caused by S. pneumoniae. MATERIALS &
      METHODS: Mice were treated intraperitoneally with monoclonal antibody (mAb) 1609
      (which inhibits both anticoagulant and cytoprotective effects of APC), mAb 1591
      (which inhibits only the anticoagulant effects of APC) or a control antibody mAb
      prior to infection with viable S. pneumoniae via the airways (to induce
      pneumonia) or via the tail vein (to induce primary sepsis). Mice were analyzed at
      24 or 48 hours after infection. RESULTS: mAb 1609, but not mAb 1591, enhanced the
      procoagulant response to pneumococcal pneumonia and sepsis, as indicated by
      elevated levels of thrombin-antithrombin complexes and D-dimer in plasma and
      lungs. mAb 1609 only modestly affected the fibrinolytic response (elevated plasma
      and lung levels of the fibrinolysis inhibitor plasminogen activator inhibitor
      type I during sepsis) and cytokine release (elevated plasma interleukin-6
      concentrations during pneumonia). CONCLUSION: The cytoprotective effects of
      endogenous APC reduce activation of coagulation during murine pneumococcal
      pneumonia and sepsis.

PMID- 25586195
TI  - Influence of polyphenols on the physiological processes in the skin.
AB  - In the last decade antioxidants from a group of polyphenols have been proposed as
      one of the most effective functional ingredients of anti-ageing properties that
      counteract the effects of oxidative damage to the skin. It has been shown that
      the use of polyphenols affects skin protection and mitigates inflammatory
      conditions of the skin. Numerous studies have confirmed that polyphenols by
      neutralizing free radicals, antioxidant activity and by their ability to chelate
      ions of transition metals can effectively reduce the level of nonprotein
      inflammatory mediators. The biological activity of polyphenols in the skin is
      primarily determined by their physicochemical properties and the ability to
      overcome the epidermal barrier as they try to reach appropriate receptors. This
      study reviews literature on the effects of polyphenols relating to the
      physiological processes in the skin and role of the major plant polyphenols in
      cosmetology and dermatology.

PMID- 25586198
TI  - Palliative radiotherapy regimens for patients with thoracic symptoms from non
      small cell lung cancer.
AB  - BACKGROUND: Palliative radiotherapy to the chest is often used in patients with
      lung cancer, but radiotherapy regimens are more often based on tradition than
      research results. This is an update of a Cochrane review first published in 2001
      and previously updated in 2006. OBJECTIVES: The two objectives of this review
      were:1. To assess the effects of different palliative radiotherapy regimens on
      improving thoracic symptoms in patients with locally advanced or metastatic non
      small cell lung cancer who are not suitable for radical RT given with curative
      intent.2. To assess the effects of radiotherapy dose on overall survival in
      patients with locally advanced or metastatic non-small cell lung cancer who are
      not suitable for radical RT given with curative intent. SEARCH METHODS: The
      electronic databases MEDLINE (1966 - Jan 2014), EMBASE and the Cochrane Central
      Register of Controlled Trials, reference lists, handsearching of journals and
      conference proceedings, and discussion with experts were used to identify
      potentially eligible trials, published and unpublished.Two authors (FM and RS)
      independently identified all studies that may be suitable for inclusion in the
      review.We updated the search up to January 2014. SELECTION CRITERIA: Randomised
      controlled clinical trials comparing different regimens of palliative thoracic
      radiotherapy in patients with non-small cell lung cancer. DATA COLLECTION AND
      ANALYSIS: The reviewers assessed search results independently and possible
      studies were highlighted and the full text obtained. Data were extracted and
      attempts were made to contact the original authors for missing information.The
      primary outcome measure was improvement in major thoracic symptoms (degree and
      duration). Secondary outcome measures were short and long term toxicities, effect
      on quality of life and overall survival.Patient reported outcomes were reported
      descriptively. Quantitative data such as survival and toxicity were analysed as
      dichotomous variables and reported using relative risks (RR).For this update of
      the review a meta-analysis of the survival data was carried out. MAIN RESULTS:
      Fourteen randomised controlled trials (3576 patients) were included, with no new
      studies added in this update.There were important differences in the doses of
      radiotherapy investigated, the patient characteristics including disease stage
      and performance status and the outcome measures.The doses of RT investigated
      ranged from 10 Gy in 1 fraction (10Gy/1F) to 60 Gy/30F over six weeks, with a
      total of 19 different dose/ fractionation regimens.Potential biases were
      identified in some studies. Methods of randomisation, assessment of symptoms and
      statistical methods used were unclear in some papers. Withdrawal and drop-outs
      were accounted for in all but one study.All 13 studies that investigated symptoms
      reported that major thoracic symptoms improved following RT.There is no strong
      evidence that any regimen gives greater palliation. Higher dose regimens may give
      more acute toxicity and some regimens are associated with an increased risk of
      radiation myelitis. Variation in reporting of toxicities, in particular the
      absence of clear grading, means results of the meta-analysis should be treated
      with caution.Meta-analysis of overall survival broken down by performance status,
      a key variable, is included in this update. Further information was sought from
      all the original authors if stratified data was not included in the original
      publication. Three published studies contained sufficient data and seven authors
      were able to provide further information which represented 1992 patients (56% of
      all patients). The absence of data for nearly half of the patients has affected
      the quality of evidence.The meta-analysis showed no significant difference in 1
      year overall survival between regimens with fewer radiotherapy fractions compared
      with regimens with more when patients were stratified by performance status. The
      results of the meta-analysis of 1-year overall survival for patients with good
      performance status (WHO performance status 0-1) showed moderately high
      heterogeneity and a summary result was not thought meaningful. The results of 1
      year overall survival for patients with poor performance status was RR 0.96 (95%
      CI 0.91 to 1.02; moderate quality of evidence). AUTHORS' CONCLUSIONS:
      Radiotherapy for patients with incurable non-small cell lung cancer can improve
      thoracic symptoms. Care should be taken with the dose to the spinal cord to
      reduce the risk of radiation myelopathy. The higher dose, more fractionated
      palliative radiotherapy regimens do not provide better or more durable palliation
      and their use to prolong survival is not supported by strong evidence. More
      research is needed into reducing the acute toxicity of large fraction regimens
      and into the role of radical compared to high dose palliative radiotherapy. In
      the future, large trials comparing different RT regimens may be difficult to set
      up because of the increasing use of systemic chemotherapy. Trials looking at how
      best to integrate these two modalities, particularly in good PS patients, need to
      be carried out.

PMID- 25586196
TI  - Cytoplasmic TAF2-TAF8-TAF10 complex provides evidence for nuclear holo-TFIID
      assembly from preformed submodules.
AB  - General transcription factor TFIID is a cornerstone of RNA polymerase II
      transcription initiation in eukaryotic cells. How human TFIID-a megadalton-sized
      multiprotein complex composed of the TATA-binding protein (TBP) and 13 TBP
      associated factors (TAFs)-assembles into a functional transcription factor is
      poorly understood. Here we describe a heterotrimeric TFIID subcomplex consisting
      of the TAF2, TAF8 and TAF10 proteins, which assembles in the cytoplasm. Using
      native mass spectrometry, we define the interactions between the TAFs and uncover
      a central role for TAF8 in nucleating the complex. X-ray crystallography reveals
      a non-canonical arrangement of the TAF8-TAF10 histone fold domains. TAF2 binds to
      multiple motifs within the TAF8 C-terminal region, and these interactions dictate
      TAF2 incorporation into a core-TFIID complex that exists in the nucleus. Our
      results provide evidence for a stepwise assembly pathway of nuclear holo-TFIID,
      regulated by nuclear import of preformed cytoplasmic submodules.

PMID- 25586197
TI  - Long-term outcomes after surgical or nonsurgical initial therapy for patients
      with T4 squamous cell carcinoma of the larynx: A 3-decade survey.
AB  - BACKGROUND: The current study was conducted to evaluate long-term disease
      control, survival, and functional outcomes after surgical and nonsurgical initial
      treatment for patients with T4 larynx cancer. METHODS: Demographics, disease
      stage, and treatment characteristics were reviewed for 221 sequential patients
      treated for T4 laryngeal squamous cell cancer at a single institution between
      1983 and 2011. Survival and disease control outcomes were calculated. RESULTS:
      The median follow-up time was 47 months (71 months for patients still alive at
      the time of analysis). The overall 5-year and 10-year overall survival rates were
      52% and 29%, respectively, and the corresponding disease-free survival rates were
      57% and 48%, respectively. Overall 5-year and 10-year locoregional control rates
      were 78% and 67%, respectively, and the corresponding rates for freedom from
      distant metastasis were 76% and 74%, respectively. On both univariate and
      multivariate analyses, lymph node-positive disease at the time of presentation
      was associated with overall mortality (P<.0001). Patients treated with
      laryngectomy followed by postlaryngectomy radiotherapy (161 patients) achieved
      better initial locoregional control than patients treated with a laryngeal
      preservation (LP) approach (60 patients) throughout the follow-up period (log
      rank P<.007) yet the median overall survival times were equal for both groups (64
      months; 95% confidence interval 47-87 months and 38-87 months, respectively [P
      =.7]). Patients treated with an LP approach had a tracheostomy rate of 45% and an
      any-event aspiration rate of 23%. Rates of high-grade dysphagia at the time of
      last follow-up were worse for patients treated with an LP approach (P<.01).
      CONCLUSIONS: Surgery and postoperative radiotherapy can produce substantial long
      term cancer control and survival rates for patients with T4 larynx cancer.
      Caution should be taken when selecting patients for initial nonsurgical treatment
      because of significant rates of functional impairment despite survival
      equivalence.

PMID- 25586199
TI  - Two novel frameshift mutations in BRCA2 gene detected by next generation
      sequencing in a survey of Spanish patients of breast cancer.
AB  - PURPOSE: To analyze BRCA1 and BRCA2 genes using a cost-effective and rapid
      approach based on next generation sequencing (NGS) technology. METHODS: A
      population of Spanish cancer patients with a personal or familial history of
      breast and/or ovarian cancer was analyzed for germline mutations in BRCA1 and
      BRCA2 genes. The methodology relies on a 5 multiplex PCR assay coupled to NGS.
      RESULTS: Ten pathogenic mutations (four in BRCA1 and six in BRCA2 gene) were
      identified in a Spanish population. The deletion c.1792delA, in exon 10, and the
      duplication c.5869dupA, in exon 11 of BRCA2 gene were not previously reported and
      should be considered as pathogenic due to its frameshift nature. CONCLUSION: Two
      novel frameshift mutations in BRCA2 gene were detected using the multiplex PCR
      based assay following by NGS.

PMID- 25586201
TI  - Reply: Letter to the editor for FullSTEP BIA in JME by Saunders et al 2014.

PMID- 25586200
TI  - Silane meets click chemistry: towards the functionalization of wet bacterial
      cellulose sheets.
AB  - The modification of cellulosic materials is of great interest in materials
      research. Wet bacterial cellulose sheets were modified by an alkoxysilane under
      mild conditions to make them accessible to click chemistry derivatization. For
      this purpose (3-azidopropyl)triethoxysilane was grafted covalently onto the
      cellulosic surface. The silanized bacterial cellulose sheets were characterized
      comprehensively by attenuated total reflectance FTIR spectroscopy, solid-state
      NMR spectroscopy, thermogravimetric analysis, SEM with energy-dispersive X-ray
      spectroscopy, and elemental analysis. To demonstrate subsequent click chemistry
      functionalization, a new fluorophore based on fluorescein was synthesized and
      clicked to the silane-modified bacterial cellulose. The new method renders
      bacterial cellulose and other never-dried cellulosic materials susceptible to
      direct and facile functionalization in an aqueous medium without the need to work
      in water-free organic phases or to employ extensive protecting group chemistry
      and functional group interconversion. 

PMID- 25586202
TI  - Re: Saunders R, Lian J, Karolicki B, Valentine W. The cost-effectiveness and
      budget impact of stepwise addition of bolus insulin in the treatment of type 2
      diabetes: evaluation of the FullSTEP trial. J Med Econ 2014;17(12):827-36.

PMID- 25586203
TI  - Comparison of differences in medical costs when new oral anticoagulants are used
      for the treatment of patients with non-valvular atrial fibrillation and venous
      thromboembolism vs warfarin or placebo in the US.
AB  - OBJECTIVE: Medical costs that may be avoided when any of the four new oral
      anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, are used
      instead of warfarin for the treatment of non-valvular atrial fibrillation (NVAF)
      were estimated and compared. Additionally, the overall differences in medical
      costs were estimated for NVAF and venous thromboembolism (VTE) patient
      populations combined. METHODS: Medical cost differences associated with NOAC use
      vs warfarin or placebo among NVAF and VTE patients were estimated based on
      clinical event rates obtained from the published trial data. The clinical event
      rates were calculated as the percentage of patients with each of the clinical
      events during the trial periods. Univariate and multivariate sensitivity analyses
      were conducted for the medical-cost differences determined for NVAF patients. A
      hypothetical health plan population of 1 million members was used to estimate and
      compare the combined medical-cost differences of the NVAF and VTE populations and
      were projected in the years 2015-2018. RESULTS: In a year, the medical-cost
      differences associated with NOAC use instead of warfarin were estimated at -$204,
      -$140, -$495, and -$340 per patient for dabigatran, rivaroxaban, apixaban, and
      edoxaban, respectively. In 2014, among the hypothetical population, the medical
      cost differences were -$3.7, -$4.2, -$11.5, and -$6.6 million for NVAF and acute
      VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban,
      respectively. In 2014, for the combined NVAF, acute VTE, and extended VTE patient
      populations, medical-cost differences were -$10.0, -$10.9, -$21.0, and -$21.0
      million for dabigatran, rivaroxaban, 2.5 mg apixaban, and 5 mg apixaban,
      respectively. Medical-cost differences associated with use of NOACs were
      projected to steadily increase from 2014 to 2018. CONCLUSIONS: Medical costs are
      reduced when NOACs are used instead of warfarin/placebo for the treatment of NVAF
      or VTE, with apixaban being associated with the greatest reduction in medical
      costs.

PMID- 25586204
TI  - The impact of lymph node size to predict nodal metastasis in patients with rectal
      cancer after preoperative chemoradiotherapy.
AB  - PURPOSE: During restaging after preoperative chemoradiotherapy (CRT), the
      assessment of lymph node (LN) metastasis is vital for selecting further treatment
      strategies. This study aimed to evaluate the impact of LN size to predict LN
      metastasis in rectal cancer patients after preoperative CRT. METHODS: A total of
      30 consecutive patients who underwent preoperative CRT followed by curative
      resection of primary rectal cancer were selected as a study group (CRT group). As
      a control group (non-CRT group), 30 patients who underwent primary tumor
      resection were selected using a 1:1 case-match design. Matching criteria were
      gender, age, and clinical T stage. The size of each LN was measured from the
      surgical specimen. To clarify optimal cutoff values for node size according to
      the risk of detecting metastasis, receiving-operator characteristic (ROC) curves
      were generated. RESULTS: In the non-CRT group, 39/474 LNs were confirmed to have
      metastasis. In the CRT group, 29/422 LNs showed metastasis. The median size of
      metastatic LNs was 6.0 mm in CRT group, which was significantly larger than 4.0
      mm in the non-CRT group (p = 0.006). The optimal cutoff value for determining
      metastasis in the CRT group was 4.5 mm, compared to 3.5 mm in the non-CRT group.
      The accuracy of the cutoff value was much higher in the CRT group (CRT vs. non
      CRT, 77.9 vs. 59.9%). CONCLUSIONS: LN size is a strong indicator for prediction
      of regional LN metastasis in rectal cancer patients after preoperative CRT,
      compared to those without CRT.

PMID- 25586205
TI  - Colonic intussusception after endoscopic volvulus decompression.

PMID- 25586206
TI  - Redo-surgery by transanal colonic pull-through for failed anastomosis associated
      with chronic pelvic sepsis or rectovaginal fistula.
AB  - PURPOSE: Redo-surgery with new colorectal (CRA) or coloanal (CAA) anastomosis for
      failed previous CRA or CAA is exposed to failure and recurrent leakage,
      especially in case of rectovaginal fistula (RVF) or chronic pelvic sepsis (CPS).
      In these two situations, transanal colonic pull-through and delayed coloanal
      anastomosis (DCAA) could be an alternative to avoid definitive stoma. This study
      aimed to assess results of such redo-surgery with DCAA for failed CRA or CAA with
      CPS and/or RVF. METHODS: All patients who underwent DCAA for failed CRA or CAA
      with CPS and/or RVF were reviewed. Success was defined as a patient without any
      stoma at the end of follow-up. Long-term functional results were assessed using
      the low anterior resection syndrome (LARS) score. RESULTS: 24 DCAA were performed
      after failed CRA or CAA with CPS (n = 15) or RVF (n = 9). Sixteen (67%) patients
      had a diverting stoma at the time (n = 5) or performed during DCAA (n = 11).
      After a mean follow-up of 29 +/- 19 months, success rate was 79% (19/24): 5
      patients had a permanent stoma because of recurrent sepsis (n = 2), anastomotic
      stricture (n = 1), or poor functional outcomes (n = 2). Functional outcomes were
      satisfactory (no or minor LARS) in 82% of the successful patients. CONCLUSION: In
      case of failed CRA or CAA with CPS or RVF, DCAA was associated with a 79% success
      rate. It could therefore be proposed as an alternative to standard redo-CRA or
      CAA when the risk of recurrent sepsis and failure with subsequent definitive
      stoma is thought to be high.

PMID- 25586207
TI  - Evolution of conductive filament and its impact on reliability issues in oxide
      electrolyte based resistive random access memory.
AB  - The electrochemical metallization cell, also referred to as conductive bridge
      random access memory, is considered to be a promising candidate or complementary
      component to the traditional charge based memory. As such, it is receiving
      additional focus to accelerate the commercialization process. To create a
      successful mass product, reliability issues must first be rigorously solved. In
      depth understanding of the failure behavior of the ECM is essential for
      performance optimization. Here, we reveal the degradation of high resistance
      state behaves as the majority cases of the endurance failure of the HfO2
      electrolyte based ECM cell. High resolution transmission electron microscopy was
      used to characterize the change in filament nature after repetitive switching
      cycles. The result showed that Cu accumulation inside the filament played a
      dominant role in switching failure, which was further supported by measuring the
      retention of cycle dependent high resistance state and low resistance state. The
      clarified physical picture of filament evolution provides a basic understanding
      of the mechanisms of endurance and retention failure, and the relationship
      between them. Based on these results, applicable approaches for performance
      optimization can be implicatively developed, ranging from material tailoring to
      structure engineering and algorithm design. 

PMID- 25586208
TI  - Managing target-specific oral anticoagulant associated bleeding including an
      update on pharmacological reversal agents.
AB  - Target-specific oral anticoagulants (TSOACs) dabigatran, rivaroxaban and apixaban
      are approved for the prevention and treatment of thromboembolism in several
      clinical settings. Bleeding is the major complication of anticoagulant therapy,
      including TSOACs, and anticoagulant reversal strategies are highly desired for
      the management of anticoagulant-associated major bleeding in addition to maximum
      supportive care and procedural/surgical intervention. Unlike VKAs for which
      vitamin K and coagulation factor replacement with prothrombin complex concentrate
      (PCC) can restore hemostasis, there are no clinically available agents proven to
      reverse TSOAC anticoagulant effect and ameliorate TSOAC-related major bleeding.
      This narrative review critically evaluates the evidence for TSOAC reversal using
      non-specific reversal agents PCC, activated PCC (APCC) and recombinant activated
      factor VII (rVIIa) which have been assessed primarily using in vitro experiments,
      animal models and healthy human volunteers. Aripazine is a novel agent undergoing
      clinical development for non-specific anticoagulant reversal, including TSOACs.
      Data are presented regarding specific reversal agents idarucizumab (dabigatran)
      and andexanet alfa (oral factor Xa inhibitors) currently being evaluated in
      clinical trials. A practical approach to management of patients with TSOAC
      associated bleeding is also provided. There is an urgent need for clinical
      studies that evaluate the efficacy and safety of reversal strategies for TSOAC
      related major bleeding with assessment of clinical outcomes such as bleeding and
      mortality. 

PMID- 25586210
TI  - Silencing the expression of the salivary sheath protein causes transgenerational
      feeding suppression in the aphid Sitobion avenae.
AB  - Aphids produce gel saliva during feeding which forms a sheath around the stylet
      as it penetrates through the apoplast. The sheath is required for the sustained
      ingestion of phloem sap from sieve elements and is thought to form when the
      structural sheath protein (SHP) is cross-linked by intermolecular disulphide
      bridges. We investigated the possibility of controlling aphid infestation by host
      induced gene silencing (HIGS) targeting shp expression in the grain aphid
      Sitobion avenae. When aphids were fed on transgenic barley expressing shp double
      stranded RNA (shp-dsRNA), they produced significantly lower levels of shp mRNA
      compared to aphids feeding on wild-type plants, suggesting that the transfer of
      inhibitory RNA from the plant to the insect was successful. shp expression
      remained low when aphids were transferred from transgenic plants and fed for 1 or
      2 weeks, respectively, on wild-type plants, confirming that silencing had a
      prolonged impact. Reduced shp expression correlated with a decline in growth,
      reproduction and survival rates. Remarkably, morphological and physiological
      aberrations such as winged adults and delayed maturation were maintained over
      seven aphid generations feeding on wild-type plants. Targeting shp expression
      therefore appears to cause strong transgenerational effects on feeding,
      development and survival in S. avenae, suggesting that the HIGS technology has a
      realistic potential for the control of aphid pests in agriculture. 

PMID- 25586211
TI  - Hot wire chemical vapor deposition chemistry in the gas phase and on the catalyst
      surface with organosilicon compounds.
AB  - CONSPECTUS: Hot wire chemical vapor deposition (HWCVD), also referred to as
      catalytic CVD (Cat-CVD), has been used to produce Si-containing thin films,
      nanomaterials, and functional polymer coatings that have found wide applications
      in microelectronic and photovoltaic devices, in automobiles, and in
      biotechnology. The success of HWCVD is largely due to its various advantages,
      including high deposition rate, low substrate temperatures, lack of plasma
      induced damage, and large-area uniformity. Film growth in HWCVD is induced by
      reactive species generated from primary decomposition on the metal wire or from
      secondary reactions in the gas phase. In order to achieve a rational and
      efficient optimization of the process, it is essential to identify the reactive
      species and to understand the chemical kinetics that govern the production of
      these precursor species for film growth. In this Account, we report recent
      progress in unraveling the complex gas-phase reaction chemistry in the HWCVD
      growth of silicon carbide thin films using organosilicon compounds as single
      source precursors. We have demonstrated that laser ionization mass spectrometry
      is a powerful diagnostic tool for studying the gas-phase reaction chemistry when
      combined with the methods of isotope labeling and chemical trapping. The four
      methyl-substituted silane molecules, belonging to open-chain alkylsilanes,
      dissociatively adsorb on W and Ta filaments to produce methyl radical and H2
      molecule. Under the typical deposition pressures, with increasing number of
      methyl substitution, the dominant chemistry occurring in the gas phase switches
      from silylene/silene reactions to free-radical short chain reactions. This change
      in dominant reaction intermediates from silylene/silene to methyl radicals
      explains the observation from thin film deposition that silicon carbide films
      become more C-rich with a decreasing number of Si-H bonds in the four precursor
      molecules. In the case of cyclic monosilacyclobutanes, we have shown that ring
      opening reactions play a vital role in characterizing the reaction chemistry. On
      the other hand, exocyclic Si-H(CH3) bond cleavages are more important in the less
      puckered disilacyclobutane molecules. Metal filaments are essential in HWCVD
      since they serve as catalysts to decompose precursor gases to reactive species,
      which initiate gas-phase reaction chemistry and thin film growth. We discuss the
      structural changes in metal filaments when exposed to various precursor gases.
      Depending on the nature of the radical intermediates formed from the hot-wire
      decomposition and subsequent gas-phase reactions, metal silicides and carbides
      can be formed. Overall, study of the gas-phase reaction chemistry in HWCVD
      provides important knowledge of the chemical species produced prior to their
      deposition on a substrate surface. This helps in identifying the major
      contributor to alloy formation on the filament itself and the film growth, and
      consequently, in determining the properties of the deposited films. An integrated
      knowledge of the gas-phase reaction chemistry, filament alloy formation, and thin
      film deposition is required for an efficient deposition of high-quality thin
      films and nanomaterials.

PMID- 25586209
TI  - Cellulose degradation: a therapeutic strategy in the improved treatment of
      Acanthamoeba infections.
AB  - Acanthamoeba is an opportunistic free-living amoeba that can cause blinding
      keratitis and fatal brain infection. Early diagnosis, followed by aggressive
      treatment is a pre-requisite in the successful treatment but even then the
      prognosis remains poor. A major drawback during the course of treatment is the
      ability of the amoeba to enclose itself within a shell (a process known as
      encystment), making it resistant to chemotherapeutic agents. As the cyst wall is
      partly made of cellulose, thus cellulose degradation offers a potential
      therapeutic strategy in the effective targeting of trophozoite encased within the
      cyst walls. Here, we present a comprehensive report on the structure of cellulose
      and cellulases, as well as known cellulose degradation mechanisms with an eye to
      target the Acanthamoeba cyst wall. The disruption of the cyst wall will make
      amoeba (concealed within) susceptible to chemotherapeutic agents, and at the very
      least inhibition of the excystment process will impede infection recurrence, as
      we bring these promising drug targets into focus so that they can be explored to
      their fullest. 

PMID- 25586212
TI  - The international Study to Predict Optimized Treatment in Depression (iSPOT-D):
      outcomes from the acute phase of antidepressant treatment.
AB  - We aimed to characterize a large international cohort of outpatients with MDD
      within a practical trial design, in order to identify clinically useful
      predictors of outcomes with three common antidepressant medications in acute
      phase treatment of major depressive disorder (MDD). The international Study to
      Predict Optimized Treatment in Depression has presently enrolled 1008 treatment
      seeking outpatients (18-65 years old) at 17 sites (five countries). At pre
      treatment, we characterized participants by symptoms, clinical history,
      functional status and comorbidity. Participants were randomized to receive
      escitalopram, sertraline or venlafaxine-extended release and managed by their
      physician following usual treatment practices. Symptoms, function, quality of
      life, and side-effect outcomes were assessed 8 weeks later. The relationship of
      anxiety to response and remission was assessed by comorbid Axis I diagnosis,
      presence/absence of anxiety symptoms, and dimensionally by anxiety symptom
      severity. The sample had moderate-to-severe symptoms, but substantial comorbidity
      and functional impairment. Of completers at week 8, 62.2% responded and 45.4%
      reached remission on the 17-item Hamilton Rating Scale for Depression; 53.3% and
      37.6%, respectively on the 16-item Quick Inventory of Depressive Symptoms.
      Functional improvements were seen across all domains. Most participants had side
      effects that occurred with a frequency of 25% or less and were reported as being
      in the "none" to minimal/mild range for intensity and burden. Outcomes did not
      differ across medication groups. More severe anxiety symptoms at pre-treatment
      were associated with lower remission rates across all medications, independent of
      depressive severity, diagnostic comorbidity or side effects. Across medications,
      we found consistent and similar improvements in symptoms and function, and a
      dimensional prognostic effect of comorbid anxiety symptoms. These equivalent
      outcomes across treatments lay the foundation for identifying potential
      neurobiological and genetic predictors of treatment outcome in this sample. 

PMID- 25586213
TI  - Immunology, genetics and microbiota in the COPD pathophysiology: potential scope
      for patient stratification.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by sustained
      inflammation of the airways, leading to destruction of lung tissue and declining
      pulmonary function. Although smoking is the most obvious risk factor for COPD,
      only about 20% of smokers develop COPD and smoking cessation does not reverse
      progression of COPD, indicating that while smoking is an important cause or
      initiating factor, it is not the only driver of ongoing chronic inflammation and
      disease progression in COPD patients. We hypothesize that smoking-induced changes
      in lung microbiota, epithelial integrity and epigenetic control of gene
      expression result in autoantigen induction and perturbed immune regulation in
      genetically vunerable individuals. In our view, COPD patients may be stratified
      according to their immunological and inflammatory status related to specific
      changes in the lung microbiota (innate and adaptive immunity), presence of
      autoantigens (adaptive immunity: Th1-B-cell axis) and epigenetic modifications
      (inflammation and structural changes). 

PMID- 25586214
TI  - Changes and predictors of radiation-induced oral mucositis in patients with oral
      cavity cancer during active treatment.
AB  - PURPOSE: Radiation-induced oral mucositis (OM) is the most debilitating side
      effect of radiation treatment in oral cavity cancer. The purpose of the study was
      to investigate change of prevalence of severe OM, OM-related symptoms, and
      predictors in oral cavity cancer patients during active treatment. METHODS AND
      SAMPLE: Longitudinal study design with repeated measures was used. Patients with
      oral cavity cancer were recruited from a head and neck outpatient radiation
      department at a major medical center in Taiwan. Patients' OM-related symptoms
      were measured at three time points. Patients' oral mucosa was assessed at nine
      time points. Generalized estimating equations (GEE) were used to analyze the
      predictive factors of prevalence of severe OM and OM-related symptoms. RESULTS:
      Patients reported highest prevalence of severe OM at T5 (5 weeks after beginning
      RT) and T6 (6 weeks after beginning radiation therapy, RT), with the combined
      chemotherapy and RT (CCRT) patients reporting a higher prevalence than those
      receiving RT alone. The peak of OM-related symptoms was at T8 (8 week after
      beginning RT), with primary symptoms of mouth pain, mouth dryness, eating
      difficulties, swallowing difficulties, and taste change. Patients with CCRT, a
      higher cumulative radiation dose, smoking, and lower body mass index (BMI) were
      at high risk to develop severe OM. OM-related symptoms were predicted by type of
      treatment, cumulative radiation dose, and smoking. CONCLUSIONS: Patients with
      oral cavity cancer suffer from OM and OM-related symptoms during aggressive RT or
      CCRT. Patient-specific oral care and emotional support are needed to relieve
      distressful OM-related symptoms during active treatment.

PMID- 25586215
TI  - A benzyl alcohol derivative of the BDPA radical for fast dissolution dynamic
      nuclear polarization NMR spectroscopy.
AB  - The synthesis, structural characterization and the successful application of a
      carbon centered radical derived from 1,3-bisdiphenylene-2-phenylallyl (BDPA), its
      benzyl alcohol derivative (BA-BDPA), as a polarizing agent for Dynamic Nuclear
      Polarization (DNP) are described. The reported BA-BDPA radical meets all the
      requirements to become a promising candidate for its use in in vivo DNP-NMR
      experiments: it is soluble in neat [1-(13)C]pyruvic acid, insoluble in the
      dissolution transfer solvent and is effective as a polarizing agent in fast
      dissolution DNP-NMR applications, without the need for using glassing agents.
      Moreover, it enables a simple but effective in-line radical filtration to obtain
      hyperpolarized solutions of [1-(13)C]pyruvic acid free of radicals that offers a
      better polarization performance. 

PMID- 25586216
TI  - Evaluation of pharmacokinetics and pharmacodynamics and clinical efficacy of
      certolizumab pegol for Crohn's disease.
AB  - INTRODUCTION: TNF-alpha antagonists have transformed the treatment of patients
      with Crohn's disease (CD). Certolizumab pegol (CZP) is the third TNF-alpha
      antagonist to be approved for use in the United States but is not currently
      approved in Europe. AREAS COVERED: This review evaluates the pharmacokinetics,
      pharmacodynamics and efficacy of CZP in CD. Safety, immunogenicity and its use in
      pregnancy have also been assessed. A literature search was conducted using Pub
      Med (2004 - 2014) for the terms 'Crohn's disease' and 'certolizumab pegol' or
      'certolizumab' or 'cimzia'. Additional studies were identified from other sources
      including citation. EXPERT OPINION: As a Fab' fragment, CZP is effective in
      binding TNF-alpha, but does not cause Fc-mediated effects. PEGylation has
      improved its pharmacokinetic profile and allowed for an increased half-life of 2
      weeks. Benefit for inducing response (an improvement in symptoms) and maintenance
      of remission has been shown. However, the benefit is less clear for the more
      stringent end-points of inducing remission and mucosal healing. There may be an
      advantage from the PEGylated formulation of CZP in terms of reduced injection
      site reactions, reduced placental transfer in pregnancy and as a treatment option
      in patients who are unable to tolerate infliximab.

PMID- 25586218
TI  - Growth of nanoparticles and microparticles by controlled reaction-diffusion
      processes.
AB  - The synthesis of different sizes of nanoparticles and microparticles is important
      in designing nanostructured materials with various properties. Wet synthesis
      methods lack the flexibility to create various sizes of particles (particle
      libraries) using fixed conditions without the repetition of the steps in the
      method with a new set of parameters. Here, we report a synthesis method based on
      nucleation and particle growth in the wake of a moving chemical front in a gel
      matrix. The process yields well-separated regions (bands) filled with nearly
      monodisperse nanoparticles and microparticles, with the size of the particles
      varying from band to band in a predictable way. The origin of the effect is due
      to an interplay of a precipitation reaction of the reagents and their diffusion
      that is controlled in space and time by the moving chemical front. The method
      represents a new approach and a promising tool for the fast and competitive
      synthesis of various sizes of colloidal particles. 

PMID- 25586220
TI  - Insight into biases and sequencing errors for amplicon sequencing with the
      Illumina MiSeq platform.
AB  - With read lengths of currently up to 2 * 300 bp, high throughput and low
      sequencing costs Illumina's MiSeq is becoming one of the most utilized sequencing
      platforms worldwide. The platform is manageable and affordable even for smaller
      labs. This enables quick turnaround on a broad range of applications such as
      targeted gene sequencing, metagenomics, small genome sequencing and clinical
      molecular diagnostics. However, Illumina error profiles are still poorly
      understood and programs are therefore not designed for the idiosyncrasies of
      Illumina data. A better knowledge of the error patterns is essential for sequence
      analysis and vital if we are to draw valid conclusions. Studying true genetic
      variation in a population sample is fundamental for understanding diseases,
      evolution and origin. We conducted a large study on the error patterns for the
      MiSeq based on 16S rRNA amplicon sequencing data. We tested state-of-the-art
      library preparation methods for amplicon sequencing and showed that the library
      preparation method and the choice of primers are the most significant sources of
      bias and cause distinct error patterns. Furthermore we tested the efficiency of
      various error correction strategies and identified quality trimming (Sickle)
      combined with error correction (BayesHammer) followed by read overlapping
      (PANDAseq) as the most successful approach, reducing substitution error rates on
      average by 93%.

PMID- 25586219
TI  - 53BP1 promotes microhomology-mediated end-joining in G1-phase cells.
AB  - Alternative non-homologous end joining (alt-NHEJ) was originally identified as a
      backup repair mechanism in the absence of classical NHEJ (c-NHEJ) factors but
      recent studies have demonstrated that alt-NHEJ is active even when c-NHEJ as well
      as homologous recombination is available. The functions of 53BP1 in NHEJ
      processes are not well understood. Here, we report that 53BP1 promotes DNA double
      strand break (DSB) repair and genomic stability not only in c-NHEJ-proficient but
      also -deficient human G1-phase cells. Using an array of repair substrates we show
      that these effects of 53BP1 are correlated with a promotion of microhomology
      mediated end-joining (MMEJ), a subtype of alt-NHEJ, in G1-phase. Consistent with
      a specific role in MMEJ we confirm that 53BP1 status does not affect c-NHEJ.
      53BP1 supports sequence deletion during MMEJ consistent with a putative role in
      facilitating end-resection. Interestingly, promotion of MMEJ by 53BP1 in G1-phase
      cells is only observed in the presence of functional BRCA1. Depletion of both
      53BP1 and BRCA1 increases repair needing microhomology usage and augments loss of
      DNA sequence, suggesting that MMEJ is a highly regulated DSB repair process.
      Together, these findings significantly expand our understanding of the cell-cycle
      dependent roles of 53BP1 in DSB repair. 

PMID- 25586222
TI  - Protein-RNA specificity by high-throughput principal component analysis of NMR
      spectra.
AB  - Defining the RNA target selectivity of the proteins regulating mRNA metabolism is
      a key issue in RNA biology. Here we present a novel use of principal component
      analysis (PCA) to extract the RNA sequence preference of RNA binding proteins. We
      show that PCA can be used to compare the changes in the nuclear magnetic
      resonance (NMR) spectrum of a protein upon binding a set of quasi-degenerate RNAs
      and define the nucleobase specificity. We couple this application of PCA to an
      automated NMR spectra recording and processing protocol and obtain an unbiased
      and high-throughput NMR method for the analysis of nucleobase preference in
      protein-RNA interactions. We test the method on the RNA binding domains of three
      important regulators of RNA metabolism.

PMID- 25586221
TI  - Defining the transcriptomic landscape of Candida glabrata by RNA-Seq.
AB  - Candida glabrata is the second most common pathogenic Candida species and has
      emerged as a leading cause of nosocomial fungal infections. Its reduced
      susceptibility to antifungal drugs and its close relationship to Saccharomyces
      cerevisiae make it an interesting research focus. Although its genome sequence
      was published in 2004, little is known about its transcriptional dynamics. Here,
      we provide a detailed RNA-Seq-based analysis of the transcriptomic landscape of
      C. glabrata in nutrient-rich media, as well as under nitrosative stress and
      during pH shift. Using RNA-Seq data together with state-of-the-art gene
      prediction tools, we refined the annotation of the C. glabrata genome and
      predicted 49 novel protein-coding genes. Of these novel genes, 14 have homologs
      in S. cerevisiae and six are shared with other Candida species. We experimentally
      validated four novel protein-coding genes of which two are differentially
      regulated during pH shift and interaction with human neutrophils, indicating a
      potential role in host-pathogen interaction. Furthermore, we identified 58 novel
      non-protein-coding genes, 38 new introns and condition-specific alternative
      splicing. Finally, our data suggest different patterns of adaptation to pH shift
      and nitrosative stress in C. glabrata, Candida albicans and S. cerevisiae and
      thus further underline a distinct evolution of virulence in yeast. 

PMID- 25586223
TI  - An ensemble strategy that significantly improves de novo assembly of microbial
      genomes from metagenomic next-generation sequencing data.
AB  - Next-generation sequencing (NGS) approaches rapidly produce millions to billions
      of short reads, which allow pathogen detection and discovery in human clinical,
      animal and environmental samples. A major limitation of sequence homology-based
      identification for highly divergent microorganisms is the short length of reads
      generated by most highly parallel sequencing technologies. Short reads require a
      high level of sequence similarities to annotated genes to confidently predict
      gene function or homology. Such recognition of highly divergent homologues can be
      improved by reference-free (de novo) assembly of short overlapping sequence reads
      into larger contigs. We describe an ensemble strategy that integrates the
      sequential use of various de Bruijn graph and overlap-layout-consensus assemblers
      with a novel partitioned sub-assembly approach. We also proposed new quality
      metrics that are suitable for evaluating metagenome de novo assembly. We
      demonstrate that this new ensemble strategy tested using in silico spike-in,
      clinical and environmental NGS datasets achieved significantly better contigs
      than current approaches. 

PMID- 25586225
TI  - Monte Carlo modelling the dosimetric effects of electrode material on diamond
      detectors.
AB  - Diamond detectors for radiation dosimetry were modelled using the EGSnrc Monte
      Carlo code to investigate the influence of electrode material and detector
      orientation on the absorbed dose. The small dimensions of the
      electrode/diamond/electrode detector structure required very thin voxels and the
      use of non-standard DOSXYZnrc Monte Carlo model parameters. The interface
      phenomena was investigated by simulating a 6 MV beam and detectors with different
      electrode materials, namely Al, Ag, Cu and Au, with thickens of 0.1 um for the
      electrodes and 0.1 mm for the diamond, in both perpendicular and parallel
      detector orientation with regards to the incident beam. The smallest
      perturbations were observed for the parallel detector orientation and Al
      electrodes (Z = 13). In summary, EGSnrc Monte Carlo code is well suited for
      modelling small detector geometries. The Monte Carlo model developed is a useful
      tool to investigate the dosimetric effects caused by different electrode
      materials. To minimise perturbations cause by the detector electrodes, it is
      recommended that the electrodes should be made from a low-atomic number material
      and placed parallel to the beam direction.

PMID- 25586224
TI  - Efficient CRISPR-rAAV engineering of endogenous genes to study protein function
      by allele-specific RNAi.
AB  - Gene knockout strategies, RNAi and rescue experiments are all employed to study
      mammalian gene function. However, the disadvantages of these approaches include:
      loss of function adaptation, reduced viability and gene overexpression that
      rarely matches endogenous levels. Here, we developed an endogenous gene
      knockdown/rescue strategy that combines RNAi selectivity with a highly efficient
      CRISPR directed recombinant Adeno-Associated Virus (rAAV) mediated gene targeting
      approach to introduce allele-specific mutations plus an allele-selective siRNA
      Sensitive (siSN) site that allows for studying gene mutations while maintaining
      endogenous expression and regulation of the gene of interest. CRISPR/Cas9 plus
      rAAV targeted gene-replacement and introduction of allele-specific RNAi
      sensitivity mutations in the CDK2 and CDK1 genes resulted in a >85% site-specific
      recombination of Neo-resistant clones versus ~8% for rAAV alone. RNAi knockdown
      of wild type (WT) Cdk2 with siWT in heterozygotic knockin cells resulted in the
      mutant Cdk2 phenotype cell cycle arrest, whereas allele specific knockdown of
      mutant CDK2 with siSN resulted in a wild type phenotype. Together, these
      observations demonstrate the ability of CRISPR plus rAAV to efficiently recombine
      a genomic locus and tag it with a selective siRNA sequence that allows for allele
      selective phenotypic assays of the gene of interest while it remains expressed
      and regulated under endogenous control mechanisms. 

PMID- 25586226
TI  - Does it get better? A longitudinal analysis of psychological distress and
      victimization in lesbian, gay, bisexual, transgender, and questioning youth.
AB  - PURPOSE: The mental health and victimization of lesbian, gay, bisexual,
      transgender, and questioning (LGBTQ) youth have garnered media attention with the
      "It Gets Better Project." Despite this popular interest, there is an absence of
      empirical evidence evaluating a possible developmental trajectory in LGBTQ
      distress and the factors that might influence distress over time. METHODS: This
      study used an accelerated longitudinal design and multilevel modeling to examine
      a racially/ethnically diverse analytic sample of 231 LGBTQ adolescents aged 16-20
      years at baseline, across six time points, and over 3.5 years. RESULTS: Results
      indicated that both psychological distress and victimization decreased across
      adolescence and into early adulthood. Furthermore, time-lagged analyses and
      mediation analyses suggested that distress was related to prior experiences of
      victimization, with greater victimization leading to greater distress. Support
      received from parents, peers, and significant others was negatively correlated
      with psychological distress in the cross-sectional model but did not reach
      significance in the time-lagged model. CONCLUSIONS: Analyses suggest that
      psychological distress might "get better" when adolescents encounter less
      victimization and adds to a growing literature indicating that early experiences
      of stress impact the mental health of LGBTQ youth.

PMID- 25586227
TI  - Drinking motives mediate cultural differences but not gender differences in
      adolescent alcohol use.
AB  - PURPOSE: To test whether differences in alcohol use between boys and girls and
      between northern and southern/central Europe are mediated by social, enhancement,
      coping, and conformity motives. METHODS: Cross-sectional school-based surveys
      were conducted among 33,813 alcohol-using 11- to 19-year-olds from northern
      Europe (Denmark, Estonia, Finland, Ireland, Poland, Scotland, and Wales) and
      southern/central Europe (Belgium, Hungary, Italy, Portugal, Slovakia, and
      Switzerland). RESULTS: Particularly in late adolescence and early adulthood, boys
      drank more frequently and were more often drunk than girls. Instead of mediation,
      gender-specific motive paths were found; 14- to 16-year-old girls drank more
      because of higher levels of coping motives and lower levels of conformity
      motives, whereas 14- to 19-year-old boys drank more because of higher levels of
      social and enhancement motives. Geographical analyses confirmed that adolescents
      from southern/central European countries drank more frequently, but those from
      northern Europe reported being drunk more often. The strong indirect effects
      demonstrate that some of the cultural differences in drinking are because of
      higher levels of social, enhancement, and coping motives in northern than in
      southern/central Europe. CONCLUSIONS: The results from the largest drinking
      motive study conducted to date suggest that gender-specific prevention should
      take differences in the motivational pathways toward (heavy) drinking into
      account, that is, positive reinforcement seems to be more important for boys and
      negative reinforcement for girls. Preventive action targeting social and
      enhancement motives and taking drinking circumstances into account could
      contribute to tackling underage drinking in northern Europe.

PMID- 25586229
TI  - Physiological indicators of pathologic video game use in adolescence.
AB  - PURPOSE: Pathologic video game use (PVGU) has been associated with a host of
      negative psychological, physical, and social outcomes during adolescence;
      however, little research has examined physiological predictors of such use. The
      purpose of the study was to examine physiological predictors of the development
      of PVGU across adolescence. METHODS: The article involves a 1-year longitudinal
      study across midadolescence. Participants were 374 adolescents and their parents
      from a large metropolitan area in the Northwest United States. PVGU was assessed
      via questionnaire, as were a number of control variables. A number of
      physiological indicators including respiratory sinus arrhythmia (RSA) and
      galvanic skin conductance (indices of parasympathetic and sympathetic nervous
      system activity, respectively) were measured during baseline, a cognitively
      stimulating task (Rubik's cube), and a family problem-solving task. RESULTS: Less
      RSA withdrawal to a cognitively simulating task was related to greater pathologic
      video game symptoms, but less RSA withdrawal to a family problem-solving task was
      associated with the presence of pathologic video game symptoms (p < .05). For
      girls only, galvanic skin conductance activation during the family problem
      solving was related to greater pathologic video game symptoms (p < .01).
      CONCLUSIONS: These findings suggest that adolescents who do not find cognitive
      tasks stimulating physiologically have a greater severity of PVGU. Additionally,
      adolescents who show physiological signs of stress in a family task were more
      likely to have PVGU symptoms and only girls have more severe PVGU levels. This
      study is the first to show that physiological indicators predict PVGU over time
      in adolescence and has important implications regarding the prevention and
      treatment of PVGU in adolescence.

PMID- 25586228
TI  - Social discrimination, stress, and risk of unintended pregnancy among young
      women.
AB  - PURPOSE: Prior research linking young women's mental health to family planning
      outcomes has often failed to consider their social circumstances and the
      intersecting biosocial mechanisms that shape stress and depression as well as
      reproductive outcomes during adolescence and young adulthood. We extend our
      previous work to investigate relationships between social discrimination, stress
      and depression symptoms, and unintended pregnancy among adolescent and young
      adult women. METHODS: Data were drawn from 794 women aged 18-20 years in a
      longitudinal cohort study. Baseline and weekly surveys assessed psychosocial
      information including discrimination (Everyday Discrimination Scale), stress
      (Perceived Stress Scale), depression (Center for Epidemiologic Studies-Depression
      Scale), and reproductive outcomes. Multilevel, mixed-effects logistic regression
      and discrete-time hazard models estimated associations between discrimination,
      mental health, and pregnancy. Baron and Kenny's method was used to test mediation
      effects of stress and depression on discrimination and pregnancy. RESULTS: The
      mean discrimination score was 19/45 points; 20% reported moderate/high
      discrimination. Discrimination scores were higher among women with stress and
      depression symptoms versus those without symptoms (21 vs. 18 points for both, p <
      .001). Pregnancy rates (14% overall) were higher among women with moderate/high
      (23%) versus low (11%) discrimination (p < .001). Discrimination was associated
      with stress (adjusted relative risk ratio, [aRR], 2.2; 95% confidence interval
      [CI], 1.4-3.4), depression (aRR, 2.4; CI, 1.5-3.7), and subsequent pregnancy
      (aRR, 1.8; CI, 1.1-3.0). Stress and depression symptoms did not mediate
      discrimination's effect on pregnancy. CONCLUSIONS: Discrimination was associated
      with an increased risk of mental health symptoms and unintended pregnancy among
      these young women. The interactive social and biological influences on
      reproductive outcomes during adolescence and young adulthood warrant further
      study.

PMID- 25586230
TI  - Serum uric acid and cardiovascular risk among Portuguese adolescents.
AB  - PURPOSE: The aim of the study was to investigate the association between serum
      uric acid (SUA) and cardiovascular risk classes (CRCs) in adolescents using a
      cluster-based approach. METHODS: A cross-sectional evaluation was carried out in
      the 2007-2008 school year, including adolescents born in 1990 and enrolled in the
      schools of Porto, Portugal. The analysis included 1,286 adolescents. To identify
      CRC, a normal mixture model was performed including several biological
      cardiovascular risk factors. A multinomial logistic regression model was applied
      to explore the association between SUA and each CRC. RESULTS: Three classes were
      extracted using model-based cluster analysis (low, medium, and high CRC). The
      high CRC accounted for the smallest proportion of participants (5.6%) and
      represented the adolescents with higher waist circumference, systolic and
      diastolic blood pressures, total cholesterol, triglycerides, and insulin levels.
      Adolescents at increased risk of cardiovascular disease had significantly higher
      mean concentrations of SUA compared with adolescents at low cardiovascular risk
      (55.0 vs. 51.5 mg/L in males and 41.9 vs. 37.6 mg/L in females). After adjustment
      and considering low CRC as reference, SUA was positively associated with high CRC
      in both sexes (odds ratio, 1.04; 95% confidence interval, 1.00-1.07 in males; and
      odds ratio, 1.04; 95% confidence interval, 1.01-1.07 in females). CONCLUSIONS:
      Among 17-year-old adolescents, SUA increases were positively associated with
      higher CRC.

PMID- 25586232
TI  - Imine-functionalised protic NHC complexes of Ir: direct formation by C-H
      activation.
AB  - N-Arylimine-functionalised protic NHC (pNHC) Ir(i) and Ir(iii) complexes are
      obtained directly from neutral or cationic Ir(i) imidazole complexes using excess
      [Ir(cod)(MU-Cl)]2 or TlPF6, respectively. N-Arylimine-functionalised imidazolium
      salts lead to imidazole or pNHC complexes by competing N-H or C-H bond activation
      depending on the type of imidazolium counterion. 

PMID- 25586231
TI  - Integrating mental health into adolescent annual visits: impact of previsit
      comprehensive screening on within-visit processes.
AB  - PURPOSE: To evaluate how a comprehensive, computerized, self-administered
      adolescent screener, the DartScreen, affects within-visit patient-doctor
      interactions such as data gathering, advice giving, counseling, and discussion of
      mental health issues. METHODS: Patient-doctor interaction was compared between
      visits without screening and those with the DartScreen completed before the
      visit. Teens, aged 15-19 years scheduled for an annual visit, were recruited at
      one urban and one rural pediatric primary care clinic. The doctor acted as
      his/her own control, first using his/her usual routine for five to six adolescent
      annual visits. Then, the DartScreen was introduced for five visits where at the
      beginning of the visit, the doctor received a summary report of the screening
      results. All visits were audio recorded and analyzed using the Roter interaction
      analysis system. Doctor and teen dialogue and topics discussed were compared
      between the two groups. RESULTS: Seven midcareer doctors and 72 adolescents
      participated; 37 visits without DartScreen and 35 with DartScreen were audio
      recorded. The Roter interaction analysis system defined medically related data
      gathering (mean, 36.8 vs. 32.7 statements; p = .03) and counseling (mean, 36.8
      vs. 32.7 statements; p = .01) decreased with DartScreen; however, doctor
      responsiveness and engagement improved with DartScreen (mean, 4.8 vs. 5.1
      statements; p = .00). Teens completing the DartScreen offered more psychosocial
      information (mean, 18.5 vs. 10.6 statements; p = .01), and mental health was
      discussed more after the DartScreen (mean, 93.7 vs. 43.5 statements; p = .03).
      Discussion of somatic and substance abuse topics did not change. Doctors reported
      that screening improved visit organization and efficiency. CONCLUSIONS: Use of
      the screener increased discussion of mental health but not at the expense of
      other adolescent health topics.

PMID- 25586233
TI  - [Chemotherapy-induced neuropathy].
AB  - BACKGROUND: Neurological sequelae of cytostatic chemotherapy are a growing
      medical problem as the number of patients suffering from malignant diseases is
      steadily increasing. OBJECTIVES: Chemotherapy-induced neuropathies (CIN) are
      among the most common side effects of many cytostatic drugs. Awareness of
      symptoms, diagnosis and treatment of these conditions are therefore highly
      relevant. METHODS: A review of the primary and secondary literature was carried
      out. RESULTS: This article reviews the literature on neuropathies induced by
      frequently used cytostatic drugs and discusses diagnostic, preventive and
      therapeutic strategies. Specifically, this review focuses on antibody-drug
      conjugates, platinum-based antineoplastic drugs, proteasome inhibitors, taxanes
      and vinca alkaloids. The lack of well-established preventive and therapeutic
      strategies complicates the management of CINs. The most successful approaches to
      CIN prevention are modifications of the treatment regime including single and
      cumulative doses, frequency and mode of infusion. Current evidence favors
      duloxetine as a symptomatic treatment of platinum-induced neuropathies.
      CONCLUSION: The CINs are an unsolved medical problem. Knowledge of symptoms as
      well as preventive, diagnostic and therapeutic strategies is important when
      patients present in clinical practice with neurological symptoms following
      chemotherapy.

PMID- 25586235
TI  - Hey Little Sister, Who's the Only One? Modulating Informativeness in the
      Resolution of Privative Ambiguity.
AB  - We present two eye-tracking experiments on the interpretation of sentences like
      "The tall girl is (not) the only one that ...," which are ambiguous between the
      anaphoric (the only girl that ...) and the exophoric interpretation (the only
      individual that ...). These interpretations differ in informativeness: in a
      positive context, the exophoric (strong) reading entails the anaphoric (weak),
      while in a negative context the entailment pattern is reversed and the anaphoric
      reading is the strongest one. We tested whether adults rely on considerations
      about informativeness in solving the ambiguity. The results show that
      participants interpreted one exophorically in both positive and negative
      contexts. Given these findings, we cast doubts on the idea that Informativeness
      plays a role in ambiguity resolution and proposes a Principle of Maximal
      Exploitation: When a context is provided, adults extend their domain of
      evaluation to include the whole scenario, independently from truth-conditional
      considerations about informativity and strength. 

PMID- 25586234
TI  - Voluntary surveillance program for equine influenza virus in the United States
      from 2010 to 2013.
AB  - BACKGROUND: Recent surveillance studies for equine respiratory viruses have shown
      that equine influenza virus (EIV) continues to be a prevalent respiratory virus
      of equids throughout the United States and Europe. OBJECTIVES: To gain a better
      understanding of the prevalence and epidemiology of EIV shed by horses, mules and
      donkeys in the United States from March 2010 to November 2013. ANIMALS: 2,605
      equids. METHODS: Nasal secretions from index cases with acute onset of
      respiratory disease were tested by qPCR for EIV. Multilevel logistic regression
      was used to model the association between EIV status and prevalence factors.
      Furthermore, observations from EIV-positive study horses were compared to
      previous data from March 2008 to February 2010. RESULTS: A total of 230 (9.7%)
      index cases tested qPCR positive for EIV. A higher-than-expected proportion of
      EIV qPCR-positive horses occurred in the 1-5, 6-10, and 11-15 age groups when
      compared to the <1 year of age group. Fever, nasal discharge and coughing were
      positively associated with EIV-positive horses. EIV qPCR-positive study cases
      were significantly older and more often vaccinated against EIV compared to EIV
      qPCR-positive animals from the 2008-2010 study period. CONCLUSIONS AND CLINICAL
      IMPORTANCE: This study provides valuable and contemporary information on the
      frequency of EIV detected by qPCR in the United States. The results also
      underscore that older and previously vaccinated horses were susceptible to EIV.

PMID- 25586236
TI  - Epidemiological implications of mobility between a large urban centre and smaller
      satellite cities.
AB  - An SIR infectious disease propagation model is considered that incorporates
      mobility of individuals between a large urban centre and smaller satellite
      cities. Because of the difference in population sizes, the urban centre has
      standard incidence and satellite cities have mass action incidence. It is shown
      that the general basic reproduction number [Formula: see text] acts as a
      threshold between global asymptotic stability of the disease free equilibrium and
      disease persistence. The case of Winnipeg (MB, Canada) and some neighbouring
      satellite communities is then considered numerically to complement the
      mathematical analysis, highlighting the importance of taking into account not
      only [Formula: see text] but also other measures of disease severity. It is found
      that the large urban centre governs most of the behaviour of the general system
      and control of the spread is better achieved by targeting it rather than reducing
      movement between the units. Also, the capacity of a satellite city to affect the
      general system depends on its population size and its connectivity to the main
      urban centre. 

PMID- 25586239
TI  - Strain assessment in the carotid artery wall using ultrasound speckle tracking:
      validation in a sheep model.
AB  - The aim of this study was to validate carotid artery strain assessment in-vivo
      using ultrasound speckle tracking. The left carotid artery of five sheep was
      exposed and sonomicrometry crystals were sutured onto the artery wall to obtain
      reference strain. Ultrasound imaging was performed at baseline and stress,
      followed by strain estimation using an in-house speckle tracking algorithm tuned
      for vascular applications. The correlation between estimated and reference strain
      was r = 0.95 (p < 0.001) and r = 0.87 (p < 0.01) for longitudinal and
      circumferential strain, respectively. Moreover, acceptable limits of agreement
      were found in Bland-Altman analysis (longitudinally: -0.15 to 0.42%,
      circumferentially: -0.54 to 0.50%), which demonstrates the feasibility of
      estimating carotid artery strain using ultrasound speckle tracking. However,
      further studies are needed to test the algorithm on human in-vivo data and to
      investigate its potential to detect subclinical cardiovascular disease and
      characterize atherosclerotic plaques.

PMID- 25586238
TI  - Distance-dependent plasmon-enhanced fluorescence of upconversion nanoparticles
      using polyelectrolyte multilayers as tunable spacers.
AB  - Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted widespread
      interests in bioapplications due to their unique optical properties by converting
      near infrared excitation to visible emission. However, relatively low quantum
      yield prompts a need for developing methods for fluorescence enhancement. Plasmon
      nanostructures are known to efficiently enhance fluorescence of the surrounding
      fluorophores by acting as nanoantennae to focus electric field into nano-volume.
      Here, we reported a novel plasmon-enhanced fluorescence system in which the
      distance between UCNPs and nanoantennae (gold nanorods, AuNRs) was precisely
      tuned by using layer-by-layer assembled polyelectrolyte multilayers as spacers.
      By modulating the aspect ratio of AuNRs, localized surface plasmon resonance
      (LSPR) wavelength at 980 nm was obtained, matching the native excitation of UCNPs
      resulting in maximum enhancement of 22.6-fold with 8 nm spacer thickness. These
      findings provide a unique platform for exploring hybrid nanostructures composed
      of UCNPs and plasmonic nanostructures in bioimaging applications.

PMID- 25586240
TI  - Evaluation of the antibacterial effects of vancomycin hydrochloride released from
      agar-gelatin-bioactive glass composites.
AB  - The aim of this work was to evaluate the perfomance of agar-gelatin (AG)
      composites and AG-containing 45S5 bioactive glass (BG) microparticles (AGBG) in
      relation to their water uptake capacity, sustained release of a drug over time,
      and antibacterial effects. The composites were fabricated by the gel-casting
      method. To impart the local drug release capacity, vancomycin hydrochloride (VC)
      was loaded in the composites in concentrations of 0.5 and 1 mg ml(-1). VC release
      was assessed in distilled water at 37  degrees C up to 72 h and quantified
      spectrophotometrically. The antibacterial activity of composites was evaluated by
      the inhibition zone test and the plate count method. The experiments were
      performed in vitro up to 48 h on three staphylococcus strains: Staphylococcus
      aureus ATCC29213, S. aureus ATCC6538 and Staphylococcus epidermidis ATCC12228.
      The results showed that the addition of BG to AG composites did not affect the
      degree of water uptake. The release of VC was significantly affected by the
      presence of BG. VC release was higher from AGBGVC films than from AGVC ones over
      prolonged incubation times. Bacterial inhibition zones were found around the
      composites. The halos were larger when the cells were put in contact with AGVC
      composites than when they were put in contact with AGBGVC ones. Nevertheless, the
      viable count method demonstrated that the composites inhibited Staphylococcus
      cell growth with no statistical differences. In conclusion, the addition of BG
      did not reflect an improvement in the parameters studied. On the other hand,
      composites loaded with VC would have a role in prophylaxis against bacterial
      infection. 

PMID- 25586241
TI  - Prognostic Value of Hepatocyte Growth Factor Receptor Expression in Patients with
      Perihilar Cholangiocarcinoma.
AB  - BACKGROUND: Although an aggressive surgical approach to perihilar
      cholangiocarcinoma (PHC) has improved survival, a prognosis of advanced PHC
      remains unsatisfactory. The overexpression of mesenchymal-epithelial transition
      factor (MET) and recepteur d'origine nantais (RON) has been shown to be
      associated with poor prognosis in some types of cancer. METHODS: One hundred
      sixty-nine patients who underwent histologically curative resection for PHC were
      subjected to immunohistochemical analysis for MET and RON. The association
      between a positive expression of MET or RON and clinicopathologic features as
      well as the patients' prognosis were analyzed. RESULTS: There were 27 patients
      (16 %) who had a positive expression for both MET and RON. Although
      clinicopathologic features in the either MET- or RON-negative group were not
      significantly different compared to the both MET- and RON-positive group, the
      prognosis tended to be worse in the patients with both MET and RON positivity.
      When the analysis was limited to patients with advanced-stage disease (stage III
      and IVa), a multivariate analysis revealed that both MET and RON positivity and
      lymph node metastasis were identified as independent poor prognostic factors.
      CONCLUSIONS: The overall survival rate for patients with both MET and RON
      positivity was worse than that with either MET or RON negativity in patients with
      advanced PHC. The poor prognosis in these patients was not associated with
      unfavorable clinicopathologic features. The examination of MET and RON expression
      in PHC may enable a tailored method for patient classification that could not
      otherwise be achieved using the conventional pathologic classification system.

PMID- 25586242
TI  - Concordance of Carcinoembryonic Antigen Ratio and Response Evaluation Criteria in
      Solid Tumors as Prognostic Surrogate Indicators of Metastatic Colorectal Cancer
      Patients Treated with Chemotherapy.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA) is widely used as a tumor marker in
      colorectal cancer (CRC). This study aimed to evaluate the role of the degree of
      change in CEA levels during the treatment period and found that the degree of
      change highly correlated with disease survival and Response Evaluation Criteria
      in Solid Tumors (RECIST) criteria in evaluating therapy response. METHODS: A
      total of 447 metastatic CRC patients treated with surgery of the primary tumor
      followed by systemic therapy at a single center from the year 2000 through 2011
      were reviewed. The degree of change in CEA levels was expressed as the CEA ratio
      (post-CEA/pre-CEA) and classified into four groups during the treatment period
      for further evaluation. The imaging change of the same population was also
      compared with the CEA ratio during the treatment period. RESULTS: The CEA ratio
      was significantly correlated with different chemotherapy regimens (p < 0.001),
      pre-treatment CEA level (p < 0.001), lymphovascular invasion (p = 0.006), and
      tumor differentiation (p = 0.018). CEA ratio and imaging change according to
      RECIST criteria were both correlated with overall survival (p < 0.001). These two
      methods for evaluating treatment response were highly correlated (p < 0.001).
      CONCLUSIONS: CEA ratio was found to be a reliable prognostic factor in stage IV
      CRC, and was highly correlated with the imaging survey according to RECIST
      criteria. Further prospective studies are essential to validate these findings.

PMID- 25586243
TI  - Somatic Mutations and Genetic Heterogeneity at the CDKN1B Locus in Small
      Intestinal Neuroendocrine Tumors.
AB  - BACKGROUND: Until recently, the genetic landscape of small intestinal
      neuroendocrine tumors (SI-NETs) was limited to recurrent copy number alterations,
      most commonly a loss on chromosome 18. Intertumor heterogeneity with
      nonconcordant genotype in paired primary and metastatic lesions also is
      described, further contributing to the difficulty of unraveling the genetic
      enigma of SI-NETs. A recent study analyzing 55 SI-NET exomes nominated CDKN1B
      (p27) as a haploinsufficient tumor suppressor gene. METHODS: This study aimed to
      determine the frequency of CDKN1B inactivation and to investigate genotype
      phenotype correlations. It investigated 362 tumors from 200 patients. All samples
      were resequenced for mutations in CDKN1B using automated Sanger sequencing. The
      expression of p27 was investigated in 12 CDKN1B mutant and nine wild type tumors.
      RESULTS: Some 8.5 % (17/200) of patients had tumors with pathogenic mutations in
      CDKN1B including 13 insertion deletions, four nonsense variants, and one stop
      loss variant. All variants with available nontumoral DNA were classified as
      somatic. Inter- and intratumor heterogeneity at the CDKN1B locus was detected
      respectively in six of ten and two of ten patients. Patients with CDKN1B mutated
      tumors had both heterogeneous disease presentation and diverse prognosis.
      Expression of the p27 protein did not correlate with CDKN1B mutation status, and
      no differences in the clinical characteristics between CDKN1B mutated and CDKN1B
      wild type tumor carriers were found. CONCLUSION: This study corroborates the
      finding of CDKN1B as a potential haplo-insufficient tumor suppressor gene
      characterized by inter- and intratumor heterogeneity in SI-NETs.

PMID- 25586244
TI  - Chemotherapy for patients with colorectal liver metastases who underwent curative
      resection improves long-term outcomes: systematic review and meta-analysis.
AB  - BACKGROUND: Hepatic resection is considered the standard of care for patients
      with resectable colorectal liver metastases (CRLM), but the benefits of using
      systemic chemotherapy for these patients have not been completely proven.
      Although systemic chemotherapy is likely to improve recurrence-free survival
      (RFS), no differences in overall survival (OS) have been demonstrated to date.
      This study aimed to compare surgery plus systemic chemotherapy, regardless timing
      of administration, with surgery alone, analyzing long-term outcomes for patients
      with CRLM who underwent liver resection with curative intent. METHODS: Systematic
      review and meta-analysis of studies published from January 1991 to December 2013
      were used to compare surgery alone and surgery plus chemotherapy for patients
      with CRLM who underwent liver resection with curative intent. All randomized
      clinical trials (RCTs) were included in the study. Selection of high-quality
      observational comparative studies (OCSs) was based on a validated tool, the
      Methodological Index for Nonrandomized Studies. Comparison of RFS and OS was
      performed using a fixed-effects model and the hazard ratio (HR). RESULTS:
      Concerning OS, 5 studies (3 RCTs and 2 OCSs) comprising 2,475 patients were
      analyzed, and chemotherapy (1,024 patients) relatively improved OS rates for 23 %
      of the patients versus surgery alone (HR, 0.77; 95 % confidence interval [CI]
      0.67-0.88; p < 0.001). Four studies, totaling 1,592 patients, reported RFS (3
      using RCTs and 1 using OCSs), showing that chemotherapy (702 patients) relatively
      improved RFS for 29 % of the patients (HR, 0.71; 95 % CI 0.61-0.83; p < 0.001).
      CONCLUSION: This meta-analysis demonstrated that the use of chemotherapy for
      patients with CRLM who underwent resection with curative intent is a worthwhile
      strategy for improving both RFS and OS.

PMID- 25586246
TI  - Recommendations for healthier hydration: addressing the public health issues of
      obesity and type 2 diabetes.
AB  - Given the rapid increase in the prevalence of overweight, obesity, type 2
      diabetes and other obesity-related conditions across the world, despite a
      plethora of evidence-based guidance for clinicians, innovative campaigns aimed at
      the general public and widespread government public health initiatives, it is
      clear that a novel approach is required. The importance of fluid intake has been
      overlooked in campaigns and guidelines and also in the clinical setting, where
      the question 'what do you drink?' is often omitted. It is a significant oversight
      that food pyramids and healthy-eating plates across the world omit fluids from
      their graphics and advice. While guidelines include recommendations on changes in
      physical activity and diet, often little or no advice is offered on the
      importance of healthier hydration practices, neglecting to highlight the
      contribution of beverages high in sugar, alcohol or additives. An
      interdisciplinary group of experts in medicine, nutrition, physiology and public
      health discussed issues surrounding healthy-hydration practices in March 2010 in
      Paris to create a consensus statement on hydration and gain of body weight and
      provide recommendations. 

PMID- 25586245
TI  - Weight loss intervention reduces the risk of kidney stone formation in a rat
      model of metabolic syndrome.
AB  - OBJECTIVES: To investigate the effect of weight loss intervention on the urinary
      stone risk parameters in a rat model of metabolic syndrome. METHODS: In a
      prevention study, 4-week-old male Otsuka Long-Evans Tokushima "Fatty" rats were
      randomly assigned to three groups: control, food-restricted and food-restricted +
      exercise-trained groups. In a treatment study, 24-week-old male Otsuka Long-Evans
      Tokushima "Fatty" rats that had already developed type 2 diabetes were randomly
      assigned to the same three groups. Blood and 24-h urine chemistry were measured
      after 16 weeks. RESULTS: In both studies, food-restricted and food-restricted +
      exercise-trained rats showed significantly higher urinary pH and higher excretion
      of urinary citrate than control rats. In the prevention study, ion-activity
      products of calcium oxalate in the food-restricted and food-restricted + exercise
      trained groups were significantly lower than that of control rats. In the
      treatment study, ion-activity products of calcium oxalate index in food
      restricted + exercise-trained rats was significantly lower than that of control
      rats. CONCLUSIONS: Weight loss intervention seems to reduce the risk of uric acid
      stone formation by improving low urine pH and calcium oxalate stone formation by
      increasing urinary citrate excretion. The present study provides the first
      theoretical evidence to support weight loss intervention programs for
      nephrolithiasis patients with metabolic syndrome.

PMID- 25586247
TI  - Qualitative content analysis of online news media coverage of weight loss surgery
      and related reader comments.
AB  - The media has the ability to affect public opinion and policy direction.
      Prevalence of morbid obesity in Canada is increasing; as is the only effective
      long-term treatment, weight loss surgery (WLS). Limited research has explored
      media re/presentations of WLS. The purpose of this study was to examine national
      online news coverage (and reader comments) of WLS using content analysis. We
      sought to understand the dominant messages being conveyed within the news texts
      and reader comments, specifically whose voice was represented, who was the
      intended audience and what was the overall tone. Articles and comments were
      retrieved from the Canadian Broadcasting Corporation news web site and analysed
      using line-by-line techniques. Articles were predominantly 'positive/supportive'
      (63%) in tone and frequently presented the voices and opinions of 'experts'
      conveying a biomedical perspective. Comments were overwhelmingly 'negative' (56%)
      and often derogatory including such language as 'piggy' and 'fatty'. Comments
      were almost exclusively anonymous (99%) and were frequently directed at other
      commenters (33%) and 'fat' people (6%). The potentially problematic nature of
      media framing and reader comments, particularly as they could relate to weight
      based stigmatization and discrimination is discussed. 

PMID- 25586248
TI  - Integrating user perspectives into the development of a web-based weight
      management intervention.
AB  - The objective of this study was to adapt the design of our weight management
      intervention to the needs, expectations and capabilities of potential users. In
      study 1, we interviewed 25 people about their experiences of weight management.
      The findings of these interviews were combined with findings from existing theory
      and research in a process of 'intervention planning' that informed the design of
      the intervention. Study 2 comprised in-depth think-aloud studies with a further
      16 people interested in using a web-based intervention to manage their weight, in
      order to elicit reactions to the intervention techniques and materials. In study
      1, overly intrusive and restrictive aspects of eating self-regulation were
      commonly cited reasons for failure to maintain weight management long-term. We
      therefore designed an intervention with a more flexible approach to autonomous
      self-regulation. This approach was broadly welcomed in study 2, but there were
      indications that some participants might have difficulty effectively implementing
      self-regulation techniques independently. A flexible and autonomous approach to
      changing eating habits is attractive to potential intervention users but may be
      difficult for some users to implement successfully. 

PMID- 25586249
TI  - Risk factors associated with the metabolic syndrome in abdominal obesity.
AB  - Obesity is associated with the metabolic syndrome. However, not all obese
      individuals have cardiovascular risk factors (CVRF). It is not clear how many
      abdominally obese individuals are free of CVRF and what distinguishes them from
      the group of obese individuals with CVRF. In this study, we aimed to assess the
      associated factors and prevalence of abdominal obesity without CVRF. In our cross
      sectional analysis, we included n = 4244 subjects from the Study of Health in
      Pomerania (SHIP), a population-based study and n = 6671 subjects from the
      Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for
      Commitment of Treatment (DETECT) study, a representative primary care study in
      Germany. We defined abdominal obesity by waist-to-height ratio (WHtR) of 0.5 or
      greater. We assessed how many subjects with abdominal obesity had CVRF based on
      the definition of the metabolic syndrome. We analysed which conditions were
      associated with the absence of CVRF in abdominal obesity. In SHIP and DETECT,
      2652 (62.5%) and 5126 (76.8%) subjects had a WHtR >= 0.5. Among those with a WHtR
      >= 0.5, 9.0% and 13.8% were free of CVRF and 49.9% and 52.7% had at least two
      CVRF in SHIP and DETECT, respectively. In both studies, after backward
      elimination, age, male sex, body mass index and high liver enzymes and
      unemployment were consistently inversely associated with the absence of CVRF.
      Among abdominally obese subjects, the prevalence of metabolically healthy
      subjects is low. Conditions consistently associated with the absence of CVRF in
      abdominal obesity are younger age, female sex, low BMI, and normal liver enzymes,
      the latter likely reflecting the absence of steatohepatitis. 

PMID- 25586250
TI  - Socio-demographic and obstetrical correlates of pre-pregnancy body mass index and
      gestational weight gain.
AB  - Both pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are
      important determinants of a healthy pregnancy outcome and may show important
      variation. To study the influence of socio-demographic and obstetrical correlates
      on pre-pregnancy BMI and GWG, data of 54 022 singleton term pregnancies were
      analysed using adjusted regression models. In 2009, in the Northern region of
      Belgium, one-third of women were overweight (21.6%) or obese (10.1%) and GWG as
      recommended by the Institute of Medicine occurred in only 28% of obese women. A
      high pre-pregnancy BMI was significantly associated with low maternal education,
      high maternal age and multiparity, belonging to ethnic minority groups and a
      lower professional state. Compared to adequate GWG, excessive GWG was more common
      in younger (<20 years) women, with higher pre-pregnancy BMI and pregnancy-induced
      hypertension. Moreover, younger (20-24 years), single women, belonging to ethnic
      minority groups showed higher odds for excessive as well as insufficient GWG,
      while those with high/highest educational level had lower odds for excessive
      (odds ratio [OR] 0.76; confidence interval [CI] 0.72-0.80) and insufficient (OR
      0.93; CI 0.89-0.98) GWG. The results of this study highlight the scale of the
      problem of maternal obesity and excessive GWG for this region and offer
      opportunities to target educational campaigns and intervention programmes in the
      clinical setting. 

PMID- 25586251
TI  - Development and validation of a new questionnaire measuring eating disordered
      behaviours post bariatric surgery.
AB  - Contextualization of post-surgery circumstances in terms of key behaviours and
      emotions related to eating is crucial for reliable screening. Disordered eating
      post surgery is characterized by frequent snacking and a sense of loss of control
      over food intake. The purpose of this study was to evaluate the psychometric
      properties of a short self-report questionnaire entitled Disordered Eating after
      Bariatric Surgery (DEBS). Results indicate that the DEBS possesses satisfactory
      psychometric properties in terms of reliability, validity, internal consistency
      and test-retest reliability. The DEBS may facilitate both systematic clinical
      evaluation and future research within the area of bariatric surgery. 

PMID- 25586252
TI  - Pharmacobezoar in an obese patient with intragastric balloon: a case revealed at
      endoscopy.
AB  - Pharmacobezoar formation is a very rare complication that occurs in cases of
      altered gastrointestinal motility or to a background of disturbed anatomy of the
      gastrointestinal tract. The case of an obese and depressed patient treated by an
      intragastric balloon for weight loss, who was revealed to have a pharmacobezoar
      during endoscopy for early balloon removal, is presented. The possible causes of
      pharmacobezoar formation in such a patient treated with an intragastric balloon
      are discussed. 

PMID- 25586253
TI  - The effect of raloxifene on symptoms and cognitive functioning in a
      postmenopausal schizophrenia patient: a case report.
AB  - We report on a 61-year-old postmenopausal female with schizophrenia included in a
      raloxifene vs. placebo clinical trial and monitored during a 12-month period
      including a 3-month withdrawal period (6-9 months) without treatment. The patient
      was treated with raloxifene 60 mg/day adjuvant to antipsychotic medication for 6
      months, medication was then withdrawn for 3 months and was reintroduced due to a
      worsening of symptoms. We assessed the patient with PANSS and other
      neuropsychological tests. The patient improved in psychopathology and cognitive
      level in some aspects related to executive functions. During 3 months without the
      drug, the patient's condition deteriorated. When the drug was reintroduced,
      improvements were again observed. Raloxifene may be useful as an adjuvant
      treatment for psychopathological symptoms and some cognitive aspects in women
      with chronic schizophrenia. 

PMID- 25586254
TI  - Synthesis of 3'-fluoro-tRNA analogues for exploring non-ribosomal peptide
      synthesis in bacteria.
AB  - Aminoacyl-tRNAs (aa-tRNAs) participate in a vast repertoire of metabolic
      pathways, including the synthesis of the peptidoglycan network in the cell walls
      of bacterial pathogens. Synthesis of aminoacyl-tRNA analogues is critical for
      further understanding the mechanisms of these reactions. Here we report the semi
      synthesis of 3'-fluoro analogues of Ala-tRNA(Ala) . The presence of fluorine in
      the 3'-position blocks Ala at the 2'-position by preventing spontaneous migration
      of the residue between positions 2' and 3'. NMR analyses showed that substitution
      of the 3'-hydroxy group by fluorine in the ribo configuration favours the S-type
      conformation of the furanose ring of terminal adenosine A76. In contrast, the N
      type conformation is favoured by the presence of fluorine in the xylo
      configuration. Thus, introduction of fluorine in the ribo and xylo configurations
      affects the conformation of the furanose ring in reciprocal ways. These compounds
      should provide insight into substrate recognition by Fem transferases and the Ala
      tRNA synthetases. 

PMID- 25586255
TI  - The lateral plane delivers higher dose than the frontal plane in biplane cardiac
      catheterization systems.
AB  - The objective of the study is to compare radiation dose between the frontal and
      lateral planes in a biplane cardiac catheterization laboratory. Tube angulation
      progressively increases patient and operator radiation dose in single-plane
      cardiac catheterization laboratories. This retrospective study captured biplane
      radiation dose in a pediatric cardiac catheterization laboratory between April
      2010 and January 2014. Raw and time-indexed fluoroscopic, cineangiographic and
      total (fluoroscopic + cineangiographic) air kerma (AK, mGy) and kerma area
      product (PKA, uGym(2)/Kg) for each plane were compared. Data for 716 patients
      were analyzed: 408 (56.98 %) were male, the median age was 4.86 years, and the
      median weight was 17.35 kg. Although median beam-on time (minutes) was 4.2 times
      greater in the frontal plane, there was no difference in raw median total PKA
      between the two planes. However, when indexed to beam-on time, the lateral plane
      had a higher median-indexed fluoroscopic (0.75 vs. 1.70), cineangiographic (16.03
      vs. 24.92), and total (1.43 vs. 5.15) PKA (p < 0.0001). The median time-indexed
      total PKA in the lateral plane is 3.6 times the frontal plane. This is the first
      report showing that the lateral plane delivers a higher dose than the frontal
      plane per unit time. Operators should consciously reduce the lateral plane beam
      on time and incorporate this practice in radiation reduction protocols.

PMID- 25586256
TI  - Heterotaxy in southern Nevada: prenatal detection and epidemiology.
AB  - We retrospectively analyzed a combination of prenatally detected and postnatally
      diagnosed patients with heterotaxic situs that included those with situs
      inversus, bilateral left-sidedness, and bilateral right-sidedness for the period
      between April 2002 and July 2014. We found a statistically higher prevalence in
      the Hispanic population of Southern Nevada of 2.7/10,000 live births (95 %
      confidence intervals of 1.7-3.9) versus the non-Hispanic population of 1.6/10,000
      live births (95 % confidence intervals of 1.1-2.1), p = 0.04. Additionally, we
      noted a high prenatal detection rate of 68 % over the 12-year period of time,
      rising to 100 % over the last 2 years.

PMID- 25586258
TI  - Micro and nanotechnologies enhanced biomolecular sensing.
AB  - This editorial summarizes some of the recent advances of micro and nanotechnology
      based tools and devices for biomolecular detection. These include the
      incorporation of nanomaterials into a sensor surface or directly interfacing with
      molecular probes to enhance target detection via more rapid and sensitive
      responses, and the use of self-assembled organic/inorganic nanocomposites that
      inhibit exceptional spectroscopic properties to enable facile homogenous assays
      with efficient binding kinetics. Discussions also include some insight into
      microfluidic principles behind the development of an integrated sample
      preparation and biosensor platform toward a miniaturized and fully functional
      system for point of care applications. 

PMID- 25586257
TI  - Recurrent stuck mitral valve: eosinophilia an unusual pathology.
AB  - Eosinophilia is a very unusual and rare cause of thrombosis of prosthetic mitral
      valve. We report a 10-year-old male child of recurrent stuck prosthetic mitral
      valve. The child underwent mitral valve replacement for severe mitral
      regurgitation secondary to Rheumatic heart disease. He had recurrent prosthetic
      mitral valve thrombosis, despite desired INR levels. There was associated
      eosinophilia. The child was treated on the lines of tropical eosinophilia with
      oral prednisolone and diethylcarbamazine, the eosinophil count dropped
      significantly with no subsequent episode of stuck mitral valve. We discuss the
      management of recurrent stuck mitral valve and also eosinophilia as a causative
      factor for the same. 

PMID- 25586259
TI  - The effect of 3-thiopheneacetic Acid in the polymerization of a conductive
      electrotextile for use in biosensor development.
AB  - Investigations were conducted to develop an electrotextile using a nonwoven
      polypropylene fiber platform conformally coated in a conductive, functionalized
      copolymer of polypyrrole and 3-thiopheneacetic acid (3TAA). The objectives of
      this study were to determine: (1) if the inclusion of 3TAA in the polymerization
      process would have an effect on the availability of binding sites in the high
      surface area electrotextile for biorecognition elements and (2) how the increase
      in the concentration of 3TAA would affect the physical characteristics of the
      coating, resistivity of the sample and availability of binding sites. It was
      found that the addition of 3TAA to the polymerization process resulted in an
      increase in the size of the polypyrrole coating, as well as the material
      resistivity and available binding sites for biorecognition elements. These
      factors were used to determine which of the tested concentrations was best for
      biosensor development. A polymer coated membrane sample containing a
      concentration within the range of 10-50 mg/mL of 3TAA was selected as the best
      for future biosensor work. 

PMID- 25586260
TI  - Comparison of surface plasmon resonance, resonant waveguide grating biosensing
      and enzyme linked immunosorbent assay (ELISA) in the evaluation of a dengue virus
      immunoassay.
AB  - Two label-free biosensor platforms, Resonance Waveguide Grating (RWG) and Surface
      Plasmon Resonance (SPR), were used to rank a large panel of anti-dengue virus NS1
      antibodies. Dengue non-structural 1 (NS1) protein is an established serological
      marker for the early detection of dengue infection. A variety of commercial
      dengue NS1 antigen capture immunoassays are available in both ELISA and lateral
      flow format. However, there is a significant scope to improve both the
      sensitivity and the specificity of those tests. The interactions of antibody (Ab)
      antigen (Ag) were profiled, with weak interactions (KD = 1-0.1 MUM) able to be
      detected under static equilibrium conditions by RWG, but not observed to under
      more rigorous flow conditions using SPR. There were significant differences in
      the absolute affinities determined by the two technologies, and there was a poor
      correlation between antibodies best ranked by RWG and the lower limit of
      detection (LLOD) found by ELISA. Hence, whilst high-throughput RWG can be useful
      as preliminary screening for higher affinity antibodies, care should be exercised
      in the assignation of quantitative values for affinity between different assay
      formats. 

PMID- 25586261
TI  - A Self-Referencing Detection of Microorganisms Using Surface Enhanced Raman
      Scattering Nanoprobes in a Test-in-a-Tube Platform.
AB  - Anisotropic nanoparticles (i.e., silver nanocubes) were functionalized with
      target-specific antibodies and Raman active tags to serve as nanoprobes for the
      rapid detection of bacteria in a test-in-a-tube platform. A self-referencing
      scheme was developed and implemented in which surface enhanced Raman
      spectroscopic (SERS) signatures of the targets were observed superimposed with
      the SERS signals of the Raman tags. The assessment through the dual signals
      (superimposed target and tag Raman signatures) supported a specific recognition
      of the targets in a single step with no washing/separation needed to a
      sensitivity of 102 CFU/mL, even in the presence of non-target bacteria at a 10
      times higher concentration. The self-referencing protocol implemented with a
      portable Raman spectrometer potentially can become an easy-to-use, field
      deployable spectroscopic sensor for onsite detection of pathogenic
      microorganisms. 

PMID- 25586262
TI  - Lab-on-a-Chip Magneto-Immunoassays: How to Ensure Contact between
      Superparamagnetic Beads and the Sensor Surface.
AB  - Lab-on-a-chip immuno assays utilizing superparamagnetic beads as labels suffer
      from the fact that the majority of beads pass the sensing area without contacting
      the sensor surface. Different solutions, employing magnetic forces, ultrasonic
      standing waves, or hydrodynamic effects have been found over the past decades.
      The first category uses magnetic forces, created by on-chip conducting lines to
      attract beads towards the sensor surface. Modifications of the magnetic landscape
      allow for additional transport and separation of different bead species. The
      hydrodynamic approach uses changes in the channel geometry to enhance the capture
      volume. In acoustofluidics, ultrasonic standing waves force um-sized particles
      onto a surface through radiation forces. As these approaches have their
      disadvantages, a new sensor concept that circumvents these problems is suggested.
      This concept is based on the granular giant magnetoresistance (GMR) effect that
      can be found in gels containing magnetic nanoparticles. The proposed design could
      be realized in the shape of paper-based test strips printed with gel-based GMR
      sensors. 

PMID- 25586263
TI  - Cell Labeling for 19F MRI: New and Improved Approach to Perfluorocarbon
      Nanoemulsion Design.
AB  - This report describes novel perfluorocarbon (PFC) nanoemulsions designed to
      improve ex vivo cell labeling for 19F magnetic resonance imaging (MRI). 19F MRI
      is a powerful non-invasive technique for monitoring cells of the immune system in
      vivo, where cells are labeled ex vivo with PFC nanoemulsions in cell culture. The
      quality of 19F MRI is directly affected by the quality of ex vivo PFC cell
      labeling. When co-cultured with cells for longer periods of time, nanoemulsions
      tend to settle due to high specific weight of PFC oils (1.5-2.0 g/mL). This in
      turn can decrease efficacy of excess nanoemulsion removal and reliability of the
      cell labeling in vitro. To solve this problem, novel PFC nanoemulsions are
      reported which demonstrate lack of sedimentation and high stability under cell
      labeling conditions. They are monodisperse, have small droplet size (~130 nm) and
      low polydispersity (<0.15), show a single peak in the 19F nuclear magnetic
      resonance spectrum at -71.4 ppm and possess high fluorine content. The droplet
      size and polydispersity remained unchanged after 160 days of follow up at three
      temperatures (4, 25 and 37  degrees C). Further, stressors such as elevated
      temperature in the presence of cells, and centrifugation, did not affect the
      nanoemulsion droplet size and polydispersity. Detailed synthetic methodology and
      in vitro testing for these new PFC nanoemulsions is presented. 

PMID- 25586264
TI  - Effect of the metastatic defect on the structural response and failure process of
      human vertebrae: an experimental study.
AB  - BACKGROUND: Pathologic vertebral fractures are associated with intractable pain,
      loss of function and high morbidity in patients with metastatic spine disease.
      However, the failure mechanisms of vertebrae with lytic defects and the failed
      vertebrae's ability to retain load carrying capacity remain unclear. METHODS:
      Eighteen human thoracic and lumbar vertebrae with simulated uncontained bone
      defects were tested under compression-bending loads to failure. Failure was
      defined as 50% reduction in vertebral body height. The vertebrae were allowed to
      recover under load and re-tested to failure using the initial criteria. Repeated
      measure ANOVA was used to test for changes in strength and stiffness parameters.
      FINDINGS: Vertebral failure occurred via buckling and fracture of the cortex
      around the defect, followed by collapse of the defect region. Compared to the
      intact vertebrae, the failed vertebrae exhibited a significant loss in
      compressive strength (59%, p<0.001), stiffness (53%, p<0.05) and flexion (70%,
      p<0.01) strength. Significant reduction in anterior-posterior shear (strength
      (63%, p<0.01) and stiffness (67%, p<0.01)) and lateral bending strength (134%,
      p<0.05) were similarly recorded. In the intact vertebrae, apart from flexion
      strength (r(2)=0.63), both compressive and anterior-posterior shear strengths
      were weakly correlated with their stiffness parameters (r(2)=0.24 and r(2)=0.31).
      By contrast, in the failed vertebrae, these parameters were strongly correlated,
      (r(2)=0.91, r(2)=0.86, and r(2)=0.92, p<0.001 respectively). INTERPRETATION:
      Failure of the vertebral cortex at the defect site dominated the initiation and
      progression of vertebral failure with the vertebrae failing via a consolidation
      process of the vertebral bone. Once failed, the vertebrae showed remarkable loss
      of load carrying capacity.

PMID- 25586265
TI  - MicroRNA-221 accelerates the proliferation of laryngeal cancer cell line Hep-2 by
      suppressing Apaf-1.
AB  - Laryngeal cancer is one of the most commonly occurring malignant cancers of the
      head and neck region. In the present study, we investigated the roles of miR-221
      in laryngeal squamous cell carcinoma cell line, Hep-2. We examined the function
      and mechanism of miR-221 in Hep-2 cells using techniques of cell biology and
      molecular pathology, such as western blotting, quantitative PCR,
      immunohistochemical staining and flow cytometry. Using a luciferase assay, the
      apoptotic protease activating factor-1 (Apaf-1) mRNA 3'-UTR was shown to have
      complementary binding sites using bioinformatics prediction software including
      TargetScan, PicTar and miRanda. In conclusion, our results showed that miR-221
      inhibition caused elevated expression levels of the Apaf-1 apoptotic pathway
      proteins caspase-3, -8 and -9. miR-221 may therefore be used as a novel
      therapeutic target for laryngeal cancer.

PMID- 25586267
TI  - Light-induced protein dimerization by one- and two-photon activation of
      gibberellic acid derivatives in living cells.
AB  - We developed a highly efficient system for light-induced protein dimerization in
      live cells using photo-caged derivatives of the phytohormone gibberellic acid
      (GA3 ). We demonstrate the application of the photo-activatable chemical inducer
      of dimerization (CID) for the control of protein translocation with high
      spatiotemporal precision using light as an external trigger. Furthermore, we
      present a new two-photon (2P)-sensitive caging group, whose exceptionally high
      two-photon cross section allows the use of infrared light to efficiently unleash
      the active GA3 for inducing protein dimerization in living cells. 

PMID- 25586268
TI  - Physical and Cognitive Impacts of Digital Games on Older Adults: A Meta-Analytic
      Review.
AB  - The purpose of this study is to examine the physical and cognitive impacts of
      digital games on older adults. We conducted five independent meta-analyses by
      reporting 58 effect sizes generated from 36 studies. Results suggested that
      playing digital games is effective in improving older adults' physical balance (g
      = 0.67), balance confidence (g = 0.46), functional mobility (g = 0.53), executive
      function (g = 0.76), and processing speed (g = 0.54). Based on the results of
      heterogeneity analysis, we conducted moderator analyses for physical balance and
      processing speed. Key findings included the following: Playing digital games can
      not only improve the physical balance of older adults living in community but
      also those living in nursing homes; the relationship between age of participants
      or amount of time of gameplay and effect size is weak and the direction of the
      relationship is not definitive.

PMID- 25586266
TI  - LPS exacerbates functional and inflammatory responses to ovalbumin and decreases
      sensitivity to inhaled fluticasone propionate in a guinea pig model of asthma.
AB  - BACKGROUND AND PURPOSE: Asthma exacerbations contribute to corticosteroid
      insensitivity. LPS is ubiquitous in the environment. It causes
      bronchoconstriction and airway inflammation and may therefore exacerbate allergen
      responses. This study examined whether LPS and ovalbumin co-administration could
      exacerbate the airway inflammatory and functional responses to ovalbumin in
      conscious guinea pigs and whether these exacerbated responses were insensitive to
      inhaled corticosteroid treatment with fluticasone propionate (FP). EXPERIMENTAL
      APPROACH: Guinea pigs were sensitized and challenged with ovalbumin and airway
      function recorded as specific airway conductance by whole body plethysmography.
      Airway inflammation was measured from lung histology and bronchoalveolar lavage.
      Airway hyper-reactivity (AHR) to inhaled histamine was examined 24 h after
      ovalbumin. LPS was inhaled alone or 24 or 48 h before ovalbumin and combined with
      ovalbumin. FP (0.05-1 mg.mL(-1) ) or vehicle was nebulized for 15 min twice daily
      for 6 days before ovalbumin or LPS exposure. KEY RESULTS: Ovalbumin inhalation
      caused early (EAR) and late asthmatic response (LAR), airway hyper-reactivity to
      histamine and influx of inflammatory cells into the lungs. LPS 48 h before and co
      administered with ovalbumin exacerbated the response with increased length of the
      EAR, prolonged response to histamine and elevated inflammatory cells. FP 0.5 and
      1 mg.mL(-1) reduced the LAR, AHR and cell influx with ovalbumin alone, but was
      ineffective when guinea pigs were exposed to LPS before and with ovalbumin.
      CONCLUSIONS AND IMPLICATIONS: LPS exposure exacerbates airway inflammatory and
      functional responses to allergen inhalation and decreases corticosteroid
      sensitivity. Its widespread presence in the environment could contribute to
      asthma exacerbations and corticosteroid insensitivity in humans.

PMID- 25586269
TI  - SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential
      vitamin C cytotoxicity.
AB  - Vitamin C is considered as an important anticancer therapeutic agent although
      this view is debatable. In this study, we introduce a physiological mechanism
      demonstrating how vitamin C exerts anticancer activity that induces cell cycle
      arrest and apoptosis. Our previous and current data reveal that p53 tumor
      suppressor is the prerequisite factor for stronger anticancer effects of vitamin
      C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be
      achieved at least partly through the downregulation of the p34SEI-1 oncoprotein.
      Our previous study showed that p34SEI-1 increases the survival of various types
      of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin
      C treatment decreases the p34SEI-1 expression at the protein level and therefore
      alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase,
      appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent
      degradation, which is dependent on p53. In summary, vitamin C increases cancer
      cell death by inducing SIAH1-mediated polyubiquitination/degradation of the
      p34SEI-1 oncoprotein in a p53-dependent manner.

PMID- 25586270
TI  - Postoperative blood transfusion strategy in frail, anemic elderly patients with
      hip fracture: the TRIFE randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Hip fracture (HF) in frail elderly patients is associated
      with poor physical recovery and death. There is often postoperative blood loss
      and the hemoglobin (Hb) threshold for red blood cell (RBC) transfusions in these
      patients is unknown. We investigated whether RBC transfusion strategies were
      associated with the degree of physical recovery or with reduced mortality after
      HF surgery. PATIENTS AND METHODS: We enrolled 284 consecutive post-surgical HF
      patients (aged >= 65 years) with Hb levels < 11.3 g/dL (7 mmol/L) who had been
      admitted from nursing homes or sheltered housing. Allocation was stratified by
      residence. The patients were randomly assigned to either restrictive (Hb < 9.7
      g/dL; < 6 mmol/L) or liberal (Hb < 11.3 g/dL; < 7 mmol/L) RBC transfusions given
      within the first 30 days postoperatively. Follow-up was at 90 days. RESULTS: No
      statistically significant differences were found in repeated measures of daily
      living activities or in 90-day mortality rate between the restrictive group
      (where 27% died) and the liberal group (where 21% died). Per-protocol 30-day
      mortality was higher with the restrictive strategy (hazard ratio (HR) = 2.4, 95%
      CI: 1.1-5.2; p = 0.03). The 90-day mortality rate was higher for nursing home
      residents in the restrictive transfusion group (36%) than for those in the
      liberal group (20%) (HR = 2.0, 95% CI: 1.1-3.6; p = 0.01). INTERPRETATION:
      According to our Hb thresholds, recovery from physical disabilities in frail
      elderly hip fracture patients was similar after a restrictive RBC transfusion
      strategy and after a liberal strategy. Implementation of a liberal RBC
      transfusion strategy in nursing home residents has the potential to increase
      survival.

PMID- 25586271
TI  - Effects of the JWA gene in the regulation of human breast cancer cells.
AB  - The present study aimed to investigate whether the JWA gene can regulate the
      proliferation, migration and invasion of human breast cancer cells through the
      MAPK signaling pathway. The role of JWA in proliferation, migration, invasion and
      apoptosis was investigated in the MDA-MB-231 human breast cancer cell line.
      Following transfection with JWA-small interfering (si)RNA, the effect of JWA on
      apoptosis was assessed by Western blot analysis, proliferation was determined
      using Transwell chambers and cell migration and invasion were analyzed by
      transwell assay. The expression levels of extracellular signal-regulated kinase
      (ERK) 1/2, CSBP/RK/Mpk2 kinase (p38) and c-Jun N-terminal kinase (JNK) were
      detected using Western blot analysis in the siRNA and control groups. The
      expression of JWA in the breast cancer cells was significantly lower compared
      with the normal breast cells. Downregulation of JWA protein levels reduced the
      apoptosis and enhanced proliferation, migration and invasion of the MDA-MB-231
      cells in vitro. The results of the Western blot analysis demonstrated that,
      compared with the control groups, the expression levels of phosphorylated (p-)p38
      decreased significantly in the JWA siRNA group. No significant changes were
      observed in the expression levels of p-ERK1/2 or p-JNK. Therefore, the JWA gene
      may regulate human breast cancer cells through the MAPK signaling pathway using
      different types of regulation.

PMID- 25586273
TI  - Erratum to: Alectinib: A Review of Its Use in Advanced ALK-Rearranged Non-Small
      Cell Lung Cancer.

PMID- 25586272
TI  - Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia.
AB  - Obinutuzumab (Gazyva((r)); Gazyvaro((r))) is an intravenously administered,
      glycoengineered, humanized, type II, anti-CD20 monoclonal antibody of the IgG1
      subclass. It is available in the EU and the USA as combination therapy with oral
      chlorambucil in adults with previously untreated chronic lymphocytic leukaemia
      (CLL). In a multinational phase III study in this patient population,
      obinutuzumab plus chlorambucil significantly prolonged progression-free survival
      compared with oral chlorambucil alone and intravenous rituximab plus oral
      chlorambucil. Significant advantages with obinutuzumab plus chlorambucil over
      chlorambucil alone and rituximab plus chlorambucil were also observed in event
      free survival, the time to a new anti-leukaemia treatment and overall response.
      The overall survival benefit with obinutuzumab plus chlorambucil is as yet
      unclear, although the most recent analysis suggests a benefit over chlorambucil
      alone. In the phase III study, obinutuzumab plus chlorambucil had a manageable
      tolerability profile in accordance with what would be expected for an anti-CD20
      antibody. Neutropenia and infusion-related reactions were the most frequently
      reported grade 3 or higher treatment-emergent adverse events. In the majority of
      patients, infusion-related reactions were mild to moderate in severity and
      occurred predominantly during the first infusion and were managed by slowing or
      temporarily halting the infusion. Thus, current evidence suggests that
      obinutuzumab plus chlorambucil is a welcome addition to the treatment options
      currently available for adults with previously untreated CLL and is recommended
      by the National Comprehensive Cancer Network guidelines as the preferred first
      option for some, including those with comorbidities. 

PMID- 25586274
TI  - Evaluation of quality of life after cardiac surgery in high-risk patients.
AB  - BACKGROUND: Conventionally, there is controversy over subjecting high-risk
      patients to cardiac operations, due to major postoperative complications. Higher
      survival rates and less morbidity as well as better quality of life can be good
      predictors of the outcome of surgery. This study evaluates the quality of life
      before and 12 months after cardiac operations on high-risk patients. METHODS: In
      this study, the European System for Cardiac Operative Risk Evaluation (EuroSCORE)
      II was used to separate high-risk patients from others. The quality of life was
      assessed using the Medical Outcomes Study 36-item Short Form Health Survey (SF
      36) before surgery and one year afterward. Based on SF-36, the score for each of
      the eight different dimensions of the quality of life was quantified; and, their
      differences between pre-surgery and post-follow up period were analyzed. RESULTS:
      126 high-risk patients were included in this study. The mean age of the patients
      was 64.29 +/- 12.35 years. The median of EuroSCORE II score in these cases was
      6.83 (6.04-25.98). The results reveal that the majority of the quality of life
      dimensions, except mental health, improved significantly after the follow-up
      period. CONCLUSION: Cardiac surgery on high-risk patients can noticeably promote
      the different aspects of their quality of life; although, such improvements
      should be considered against surgical complications.

PMID- 25586275
TI  - Single-patch fold-back technique for augmentation of the superior vena cava in
      sinus venosus atrial septal defect associated with partial anomalous pulmonary
      venous return.
AB  - Sinus venosus atrial septal defect (ASD) is usually associated with partial
      anomalous pulmonary venous return (PAPVR) of the right pulmonary veins to the
      superior vena cava (SVC), or to the SVC-right atrial junction. Standard procedure
      for repair of this defect is a patch roofing of the sinus venosus ASD and
      rerouting of pulmonary veins. However, the presence of SVC stenosis is a
      complication of this technique, and SVC augmentation is necessary in some cases.
      We present a simple technique for concomitant closure of sinus venosus ASD
      associated with PAPVR and augmentation of the SVC with a single autologous
      pericardial patch. 

PMID- 25586276
TI  - An unusual association: right atrial myxoma and severe left ventricular
      dysfunction. Case report and review of the literature.
AB  - Myxomas comprise 50% of all benign cardiac tumors in adults, with the right
      atrium as their second most frequent site of origin. Surgical resection is the
      only effective therapeutic option for patients with these tumors. The association
      between right atrial myxomas and severe left ventricular systolic dysfunction is
      extremely rare and makes treatment even more challenging. This was the case for
      our patient, a 47-year-old male with a right atrial mass and a severely impaired
      left ventricular function, with a 20% ejection fraction. Global enlargement of
      the heart was also noted, with moderate right ventricular dysfunction. The tumor
      was successfully excised using the on-pump beating heart technique, with an
      immediate postoperative improvement of the left ventricular ejection fraction to
      35%. The technique proved useful, with no increased risk to the patient. 

PMID- 25586277
TI  - Frontal planar QRS/T angle can be a prognostic factor in the early postoperative
      period of patients undergoing coronary bypass surgery.
AB  - BACKGROUND: Wide QRS/T angle reflects the ventricular repolarization
      heterogeneity and has been found in association with cardiac morbidity and
      mortality in various study populations. However, literature data about the
      availability of QRS/T angle in patients undergoing cardiac surgery has not yet
      been available. METHODS: A total of 157 patients who underwent isolated coronary
      artery bypass surgery were included in this study. A preoperative 12-lead ECG was
      obtained one day before surgical procedure. The absolute difference between the
      frontal QRS wave axes and T-wave axes was defined as frontal planar QRS/T angle.
      Afterwards, patients were divided into two groups according to their frontal
      planar QRS/T angle (the cut-off value as 90 degrees ). RESULTS: Group 1 consisted
      of 109 patients with frontal planar QRS/T angle of <90, and the remaining 48
      patients with frontal planar QRS/T angle 90 were placed into group 2. Mean
      EuroSCORE was much higher in group 2. There were significant differences for
      positive inotropic agent usage (27.5% for group 1 versus 58.3% for group 2, P <
      .001) and the prevalence of postoperative atrial fibrillation (11.9% for group 1
      versus 31.2% for group 2, P = .004) between the two groups. In multivariate
      logistic regression analysis, used to determine the independent predictors of
      positive inotropic usage in the early postoperative period, only frontal planar
      QRS/T angle (OR: 0.989, 95% CI: 0.981-0.997, P = .008) and EuroSCORE (OR: 0.792,
      95% CI: 0.646-0.971, P = .025) were found to be statistically significant.
      CONCLUSION: We found that frontal planar QRS/T angle might be an important
      preoperative parameter in predicting the need for inotropic drugs in the early
      postoperative period following coronary artery bypass surgery.

PMID- 25586278
TI  - Entrapped thrombus in a foramen ovale causing pulmonary emboli treated with
      emergent surgery. Literature review.
AB  - A 60-year-old woman was admitted due to massive bilateral pulmonary
      thromboembolism and entrapped thrombus in the patent foramen ovale and severe
      right ventricular dysfunction. The patient underwent on-pump/beating heart
      removal of the intracardiac thrombus and bilateral pulmonary embolectomy. The
      postoperative course was uneventful. The chosen surgical strategy seems to offer
      excellent outcome in patients with severe right ventricular dysfunction. 

PMID- 25586279
TI  - Readmission to the intensive care unit in times of minimally invasive cardiac
      surgery: does size matter?
AB  - OBJECTIVES: It is well known that patients who undergo readmission to an
      intensive care unit (ICU) after cardiac surgery face an increased risk of
      morbidity and mortality. The present study sought to evaluate whether less
      invasive procedures might be associated with a reduction of this economically as
      well as individually important problem. The role of the quantity of ICU and
      intermediate care (IMC) beds was investigated as well. METHODS: Altogether, we
      reviewed 5,333 patients who underwent cardiac surgery in our department between
      2005 and 2010. The incidence of and reasons for readmission were determined with
      regard to individual subgroups, particularly comparing minimally invasive
      procedures with conventional strategies. RESULTS: A total of 5,132 patients were
      primarily discharged from the ICU. Out of this group, 293 patients were
      readmitted to the ICU at least once. After readmission, the average length of
      stay in the hospital was 21.9 +/- 11.3 days compared to 12.8 +/- 5.0 days in all
      other patients. Comparing the readmission rate in separate years, it was evident
      that this rate decreased with a growing ICU and IMC capacity. In patients who
      underwent less invasive cardiac surgery (ie, minimally invasive cardiac surgery,
      off-pump coronary artery bypass grafting), the readmission rates were
      significantly lower than in the entirety of patients studied. CONCLUSION:
      Readmission to the ICU after cardiac surgery is associated with impaired outcome.
      Extended resources in terms of ICU and IMC capacity may positively influence this
      problem by decreasing the number of readmissions. Modern surgical strategies with
      less invasive procedures may be associated with a reduced incidence of
      readmission as well.

PMID- 25586280
TI  - Relationship between nadir hematocrit during cardiopulmonary bypass and
      postoperative hyperglycemia in nondiabetic patients.
AB  - BACKGROUND: Hyperglycemia is common after cardiac surgery in both diabetic and
      nondiabetic patients and is associated with increased morbidity and mortality.
      Association between nadir hematocrit levels on cardiopulmonary bypass (CPB) and
      postoperative hyperglycemia is not clear. This study was carried out to determine
      the relationship between nadir hematocrit during CPB and postoperative
      hyperglycemia in nondiabetic patients. METHODS: Records of 200 nondiabetic
      patients undergoing coronary artery bypass grafting operation were
      retrospectively reviewed. In the first analysis, patients were divided into two
      subgroups according to the presence or absence of hyperglycemia. Further analysis
      was made after dividing the patients into 3 subgroups according to nadir
      hematocrit levels on CPB (less than 20%; 20% to 25%; greater than or equal to
      25%). RESULTS: Compared to patients without hyperglycemia, patients with
      postoperative hyperglycemia had significantly lower preoperative hematocrit
      levels (p = 0.004) and were associated with lower nadir hematocrit levels during
      CPB (p= 0.002). Peak intensive care unit blood glucose levels and number of blood
      transfusions were significantly higher in patients with nadir hematocrit levels
      less than 20. (p<0.001 and p<0.001 respectively). Logistic regression analysis
      demonstrated that nadir hematocrit levels less than 20% (OR 2.9, p=0.009) and
      allogenic blood transfusion (OR 1.5, p=0.003) were independently associated with
      postoperative hyperglycemia. CONCLUSIONS: Nadir hematocrit levels on CPB less
      than 20% and allogenic blood transfusions were independently associated with
      postoperative hyperglycemia in nondiabetic patients. Patients with a nadir
      hematocrit levels less than 20 % during CPB should be closely monitored for
      hyperglycemia in the perioperative period.

PMID- 25586281
TI  - Predictive factors of supraventricular arrhythmias after noncardiac thoracic
      surgery: a multicenter study.
AB  - BACKGROUND: Supraventricular cardiac arrhythmias are the most common rhythm
      disturbances in patients following thoracic surgery. The purpose of our study was
      to determine which of the clinical parameters are the most valuable in predicting
      postoperative atrial fibrillation (AF) after lung surgery. METHODS: Retrospective
      analysis was carried out on 987 patients after noncardiac thoracic surgery to
      define the prevalence, associated risk factors, and clinical course of
      postoperative arrhythmias. There were 822 men and 165 women, age 34 to 78 years
      (mean age: 61 +/- 8 years). The patients were divided into two groups depending
      on the occurrence or absence of supraventricular arrhythmia. Group I consisted of
      876 patients who were free from rhythm disturbances. The remaining 111 patients
      exhibited episodes of supraventricular arrhythmia (29 supraventricular
      tachycardia; 82 AF). These 111 patients were placed in Group II. Preoperative,
      operative, and postoperative data were reviewed. Statistical analysis was
      performed. RESULTS: A statistically significant difference was found between the
      two groups in age, previous history of heart disease, and lung resection,
      especially pneumonectomy. CONCLUSION: Age, history of prior heart disease, lung
      resection, and the extent of pulmonary resection are the main risk factors for
      postoperative supraventricular arrhythmia in patients undergoing major thoracic
      operations.

PMID- 25586282
TI  - Evaluation of myocardial contractility determination with tissue tracking
      echocardiography after levosimendan infusion in patients with poor left
      ventricular function and hemodynamics.
AB  - BACKGROUND: The aim of this study was to assess the effect of conventional
      inotropic drugs compared to levosimendan using tissue tracking echocardiography
      in the early postoperative period for patients with low ejection fraction
      undergoing coronary artery bypass graft (CABG) surgery. METHODS: We prospectively
      analyzed 115 patients (69 male, 46 female) who planned for elective coronary
      artery bypass surgery with low ejection fraction, <=% 30, from September 2012 to
      December 2013. Patients were divided into two groups. Levosimendan was used at a
      loading dose of 15 MUg/kg/min for the first twenty minutes, and continued at a
      maintenance dose of 0.2 MUg/kg/min six hours before the anesthetic induction in
      group I (n = 47, 23 male, mean age 67.16 +/- 4.72 years). Dopamine at 10
      MUg/kg/min and/or dobutamine at 10 MUg/kg/min were used at the time of weaning
      from cardiopulmonary bypass in group II (n = 68, 47 male, mean age 65.43 +/- 6.12
      years). The patients were evaluated preoperatively and on the fifth postoperative
      day by transthoracic echocardiography. Patients were also evaluated just before
      the cardiopulmonary bypass and at the 12th and 24th hours on the first
      postoperative day by transesophageal echocardiography. Student t test and chi2
      test were used for statistical analyses. RESULTS: There were no significant
      differences in demographics and preoperative hemodynamic parameters between
      groups I and II. Hemodynamic and echocardiographic parameters were significantly
      better in group I receiving levosimendan, compared to group II. CONCLUSION:
      Levosimendan enhances functional myocardial tissue mass and ensures positive
      hemodynamic effect in the early postoperative period in patients with low
      ejection fraction undergoing elective CABG.

PMID- 25586283
TI  - Pericardiectomy: prompt surgical management of constrictive pericarditis.
AB  - BACKGROUND: Constrictive pericarditis is a slow progressive fibrosis of the
      pericardium leading to a variety of symptoms and signs over time. The disease
      poses a diagnostic challenge; restrictive cardiomyopathy and other syndromes
      associated with right-sided pressure abnormalities share similar symptoms and
      clinical findings. Pericardiectomy is considered the treatment of choice for
      constrictive pericarditis. Here we studied the effects of total radical
      pericardiectomy on hemodynamics in 37 patients diagnosed with constrictive
      pericarditis. METHODS: Between 2005 and 2012 thirty-seven patients, 31 males and
      6 females, age range 15 to 69 years, underwent total pericardiectomy for
      constrictive pericarditis. Diagnosis was made on the basis of clinical,
      pathological and diagnostic modalities-ECG, x-rays, magnetic resonance imaging,
      computed tomography and echocardiogram. The surgical approach was median
      sternotomy and surgery was conducted without cardiopulmonary bypass. RESULTS:
      Postoperative outcomes showed overall improvement in the majority of patients.
      Hemodynamics-stroke volume, cardiac output, ejection fraction, central venous
      pressure-were all measurably improved postoperatively. There was no postoperative
      mortality. CONCLUSION: Radical pericardiectomy is a demonstrably useful procedure
      for correction of hemodynamic abnormalities and improvement of overall heart
      function in symptomatic patients with constrictive pericarditis.

PMID- 25586285
TI  - On peer review.

PMID- 25586284
TI  - Internal pudendal perforator artery-based gull wing flap for vulvovaginal 3D
      reconstruction after tumour excision: a new flap.
AB  - Various skin tumours such as squamous cell carcinoma and extramammary Paget's
      disease can occur in the vulval area, and reconstruction of the vulval area can
      be a very challenging task. A retrospective analysis of vulvar reconstruction
      using the new method 'internal pudendal perforator artery-based gull wing flap'
      was performed from April 2012 to December 2013. A perforator vessel from the
      internal pudendal artery was detected with a portable Doppler and marked, and
      this was the pivot point around which the flap was rotated. The flap was rotated
      by more than 150 degrees -180 degrees  internally, and the labium and the
      external wall of the vagina were reconstructed with sufficient volume. Anatomical
      and aesthetic reconstruction of the labium and the vagina was performed without
      serious complications. Functional and aesthetic vulvar reconstruction can be
      achieved by using a flap that provides sufficient volume of the labium. Our new
      technique, the 'internal pudendal perforator artery-based gull wing flap', is
      good and it can be used to reconstruct a functional and aesthetically acceptable
      vulvovagina for large defect wound after tumour excision. 

PMID- 25586286
TI  - Editorial for issue 3 of 2014, Journal of Evidence Based Medicine.

PMID- 25586291
TI  - Education section--the value of constant accumulation, need for confirmatory
      replication, and waste of unnecessary duplication.

PMID- 25586293
TI  - Ethnicity, race, and socioeconomic status influence incidence of Langerhans cell
      histiocytosis.
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease, and its
      etiology is not well understood. Population-based studies may contribute to
      etiologic research by defining incidence patterns. This study was designed to
      evaluate the descriptive epidemiology of disseminated LCH in the United States,
      using data from population-based cancer registries. PROCEDURE: We analyzed the
      incidence and survival of disseminated LCH in children and adolescents (0-19
      years) from 18 SEER registries during 2000-2009. Age-standardized incidence rates
      (ASIR) per million and rate ratios (RR) were calculated by gender, race,
      ethnicity, age, and socioeconomic variables (crowding, rural/urban, education,
      and poverty) using the SEER*Stat software 8.0.1. Relative survival (RS) estimates
      were calculated using Ederer II method. RESULTS: One hundred forty-five cases of
      disseminated LCH were recorded; ASIR was 0.70/million per year. Lower ASIR was
      observed for blacks (vs. whites) (RR = 0.41, 95% CI 0.18-0.81), while higher ASIR
      was noted for Hispanics (vs. non-Hispanics) (RR = 1.63, 95% CI 1.15-2.29). Risk
      of LCH was higher in crowded counties (RR = 1.84, 95% CI 1.31-2.58) and also in
      areas with low educational level (RR = 1.49, 95% CI 1.02-2.22). Five-year
      relative survival was 90.0% (95% CI 83.0-94.2). Important differences in survival
      were noted according to gender (male: RS = 96.0 vs. female: RS = 83.4%, P =
      0.029) and age (<1 year: RS = 78.5, 1-4 years: RS = 95.6%, 5-19 years: RS = 100%,
      P = 0.004). CONCLUSIONS: This population-based study shows significant variations
      in the incidence of disseminated LCH by race and ethnic group, as well as the
      influence of socioeconomic factors. These data may provide clues to causation and
      point toward the need for analytical epidemiologic studies.

PMID- 25586294
TI  - Initiation of aripiprazole once-monthly in patients with schizophrenia.
AB  - OBJECTIVE: This article provides rationale for recommendations on how to initiate
      aripiprazole once-monthly 400 mg (AOM 400), an injectable suspension, in patients
      with schizophrenia, supported by pharmacokinetic (PK) data and based on clinical
      studies. METHODS: An overview of data from a PK study, PK simulations, controlled
      clinical trials, and a naturalistic study is presented. RESULTS: Pharmacokinetic
      data support 400 mg as the starting and maintenance dose of AOM; the plasma
      concentration profile of aripiprazole after initiating AOM 400 was consistent
      with therapeutic concentrations observed with oral aripiprazole 10 to 30 mg/d. PK
      simulations and observed data from a single-dose clinical trial indicate that
      median aripiprazole plasma concentrations reach therapeutic levels within 7 days
      of initiating AOM 400. Because of interpatient variability, a 14-day overlap with
      oral aripiprazole or another antipsychotic medication is considered sufficient to
      ensure therapeutic concentrations. In clinical studies, when patients initiated
      AOM 400 with concomitant oral aripiprazole (10-15 mg/d based on stabilized dose)
      or continued their previous antipsychotic for <=14 days, mean aripiprazole plasma
      concentration after 4 weeks (93 to 112 ng/mL) was in range of the therapeutic
      window established for aripiprazole (94.0-534.0 ng/mL). In clinical studies, the
      400-mg starting dose of AOM was efficacious and well tolerated. Across studies of
      variable duration and design, 1296/1439 (90.1%) patients initiated AOM 400 and
      required no dose change. Overall rates of discontinuation due to lack of efficacy
      across clinical studies were low in patients treated with AOM 400 (range, 2.3%
      10.0%). In a post hoc analysis from a naturalistic study, cross-titration from
      other oral antipsychotic therapies to oral aripiprazole before initiating AOM 400
      was better tolerated with a >1- to 4-week cross-titration period versus a <=1
      week period, as evidenced by lower rates of discontinuation due to adverse events
      during cross-titration (2.7% [7/239] vs 10.4% [5/48]). The efficacy and safety of
      AOM 400 in the month after initiation in the pivotal maintenance studies were
      comparable between subpopulations of patients previously stabilized on 10- or 30
      mg doses of oral aripiprazole. CONCLUSIONS: Findings from PK data, PK
      simulations, and clinical studies all support that 400 mg is the appropriate
      initiation dose of AOM for patients with schizophrenia. When switching to oral
      aripiprazole before initiating AOM 400, tapering the prior oral antipsychotic
      while titrating up the oral aripiprazole dose (target dose 10-30 mg/d) over >1 to
      4 weeks may be an effective strategy. The efficacy, safety, and tolerability of
      AOM 400 were comparable regardless of whether patients were previously stabilized
      on oral aripiprazole 10 or 30 mg/d or other antipsychotic therapy and continued
      to receive the same oral antipsychotic for the first 14 days after initiating AOM
      400.

PMID- 25586295
TI  - Assessment of the efficacy and tolerability of clopidogrel napadisilate in Korean
      patients with coronary stenting: a multicenter, prospective, open-label,
      randomized trial.
AB  - OBJECTIVE: Clopidogrel is indicated for the treatment and prevention of
      peripheral vascular, cerebrovascular, and coronary artery diseases. This clinical
      trial was designed to demonstrate that clopidogrel napadisilate (CN) is not
      inferior to clopidogrel bisulfate (CB) with respect to its effectiveness in
      inhibiting platelet aggregation. METHODS: This 4 week multi-center, prospective,
      open-label, randomized trial was conducted at five clinical centers in South
      Korea. Patients were randomized into the 75 mg CN group or the 75 mg CB group.
      Platelet aggregation was assessed by the VerifyNow assay. The primary outcome was
      the difference of the percentage P2Y12 inhibition and the secondary outcome was
      the baseline and change in P2Y12 reaction units (PRU). RESULTS: There was no
      significant difference in the percentage P2Y12 inhibition (CN vs. CB, 34.92 +/-
      21.33% vs. 30.43 +/- 17.90%, p=0.203). The mean difference of the percentage
      P2Y12 inhibition between groups was 4.49%, their two-sided 95% confidence
      interval was -2.45% to 11.44%, and the lower bound (-2.45%) was greater than the
      acceptable non-inferiority margin of -9.0%. The baseline PRU was 96.67 +/- 76.76
      in the CN group and 216.95 +/- 68.86 in the CB group (p=0.121), and the change in
      the PRU was -3.32 +/- 51.71 in the CN group and 10.52 +/- 43.31 in the CB group
      (p=0.106). Four subjects experienced AEs (6.3%, 5 events) in the CN group and 7
      subjects (11.11%, 13 events) in the CB group without statistical significance
      (p=0.364). With respect to serious adverse events, 2 events were reported in 2
      subjects, 1 in each group. CONCLUSION: Clopidogrel napadisilate was not inferior
      to clopidogrel bisulfate in terms of antiplatelet efficacy and tolerability, and
      there were no clinically significant adverse events.

PMID- 25586296
TI  - Impact of postsurgical opioid use and ileus on economic outcomes in
      gastrointestinal surgeries.
AB  - OBJECTIVES: To assess the incidence and economic impact of postoperative ileus
      (POI) following laparotomy (open) and laparoscopic procedures for colectomies and
      cholecystectomies in patients receiving postoperative pain management with
      opioids. METHODS: Using the Premier research database, we retrospectively
      identified adult inpatients discharged between 2008 and 2010 receiving
      postsurgical opioids following laparotomy and laparoscopic colectomy and
      cholecystectomy. POI was identified through ICD-9 diagnosis codes and
      postsurgical morphine equivalent dose (MED) determined. RESULTS: A total of
      138,068 patients met criteria, and 10.3% had an ileus. Ileus occurred more
      frequently in colectomy than cholecystectomy and more often when performed by
      laparotomy. Ileus patients receiving opioids had an increased length of stay
      (LOS) ranging from 4.8 to 5.7 days, total cost from $9945 to $13,055 and 30 day
      all-cause readmission rate of 2.3 to 5.3% higher compared to patients without
      ileus. Patients with ileus received significantly greater MED than those without
      (median: 285 vs. 95 mg, p < 0.0001) and were twice as likely to have POI. MED
      above the median in ileus patients was associated with an increase in LOS (3.8 to
      7.1 days), total cost ($8458 to $19,562), and readmission in laparoscopic
      surgeries (4.8 to 5.2%). Readmission rates were similar in ileus patients
      undergoing open procedures regardless of MED. CONCLUSIONS: Use of opioids in
      patients who develop ileus following abdominal surgeries is associated with
      prolonged hospitalization, greater costs, and increased readmissions.
      Furthermore, higher doses of opioids are associated with higher incidence of POI.
      Limitations are related to the retrospective design and the use of administrative
      data (including reliance on ICD-9 coding). Yet POI may not be coded and therefore
      underestimated in our study. Assessment of pre-existing disease and preoperative
      pain management was not assessed. Despite these limitations, strategies to reduce
      opioid consumption may improve healthcare outcomes and reduce the associated
      economic impact.

PMID- 25586297
TI  - Comparison of the long term cardiac effects associated with 9 and 52 weeks of
      trastuzumab in HER2-positive early breast cancer.
AB  - PURPOSE: Trastuzumab induced cardiotoxicity (TIC) was defined as the most serious
      side effect. Long term cardiac effects of trastuzumab are still not known, thus
      we aimed to compare the long term cardiac effects of adjuvant trastuzumab
      therapies of HER2-positive breast cancer according to the treatment duration.
      METHODS: Patients who completed adjuvant trastuzumab treatment at least 6 months
      before for the adjuvant setting in HER2-positive breast cancer were included in
      the study. A total of 164 patients were included in this study: 108 and 56
      patients were treated with 9 weeks and 52 weeks of trastuzumab, respectively. The
      main limitation of our study is that due to the cross-sectional evaluation of
      cardiac biomarkers we cannot predict the status of baseline cardiac biomarkers of
      this population. RESULTS: The median follow-up of the study was 32 (10-95)
      months. The accompanying chronic diseases were similar in both groups. Baseline
      left ventricular ejection fraction (LVEF) was 65.5 +/- 3.4% vs 67.1 +/- 4.5% in
      the 9 weeks and 52 weeks trastuzumab treatment groups, respectively (p = 0.13).
      Symptomatic heart failure was not observed during trastuzumab treatment in either
      group. Trastuzumab induced cardiotoxicity (TIC) was observed in 2 (1.9%) and 17
      (30.3%) patients in the 9 and 52 weeks trastuzumab treatment groups, respectively
      (p < 0.001). After a median 24 months of follow-up from the last dose of
      trastuzumab, mean LVEF values were similar between the two treatment arms (p =
      0.29). In the subgroup analyses, mean LVEF values were significantly lower in
      patients who developed TIC compared to those who did not develop TIC (61.9 +/-
      3.6% vs 64.4 +/- 2.6%, p = 0.04). Average mean LVEF loss from baseline was
      significantly higher in patients who developed TIC compared to those who did not
      develop TIC (10.0 +/- 6.0% vs 1.5 +/- 6.2%, p < 0.001). Cardiac biomarkers were
      similar in both treatment groups. In the subgroup analyses serum High-sensitivity
      C-reactive protein (hs-CRP) and prohormone brain natriuretic peptide (pro-BNP)
      levels were significantly higher in patients who developed TIC compared to those
      who did not develop TIC. CONCLUSIONS: TIC was observed to be significantly higher
      in the 52 weeks trastuzumab group. At the end of 32 months of follow-up mean LVEF
      values and cardiac biomarkers were similar between the two treatment groups. In
      the subgroup analyses, significant LVEF loss and higher cardiac biomarkers which
      show cardiac damage in patients who developed TIC can be permanent in some of the
      patients and long term cardiac damage may be underestimated.

PMID- 25586298
TI  - An open-label extension study to evaluate the safety of ropinirole prolonged
      release in Chinese patients with advanced Parkinson's disease.
AB  - OBJECTIVE: This open-label extension (OLE) study evaluated the safety profile of
      ropinirole prolonged release (PR) administered for 24 weeks as adjunctive to
      levodopa in Chinese patients with advanced Parkinson's disease (PD). METHODS:
      This was a 24 week, flexible-dose, OLE study in Chinese patients with advanced PD
      who received 24 week treatment with ropinirole PR in the preceding double-blind
      (DB), phase III study (NCT01154166) and had no break in receiving study treatment
      while switching from the DB study to the OLE study. In the OLE study, patients
      received ropinirole PR once daily, starting with 2 mg/d and increasing up to 8
      mg/d at week 4 (2 mg increment/week); if tolerable, the dose could be further
      increased in 4 mg increments up to 24 mg/d according to clinical judgment. There
      were no efficacy assessments. Safety assessments included monitoring adverse
      events (AEs), neurological examination, Gambling Symptom Assessment Scale
      questionnaire, liver chemistry, and laboratory tests. RESULTS: Of the 295
      enrolled patients, 282 completed the study. The most common reason for withdrawal
      was AEs (n = 9, 3.1%). The mean duration to ropinirole PR treatment was 173.1
      days and an overall median daily dose of ropinirole was 8 mg (range: 2-24 mg).
      Overall, 114 (38.6%) patients experienced on-treatment AEs; the most frequent
      reported AEs ( >= 2%) were dyskinesia (6.1%), dizziness (4.1%), nausea (3.4%),
      hallucinations (3.4%), somnolence (2.7%) and decreased weight (2.4%). Sixty-eight
      patients (23.1%) experienced treatment-related AEs. Six patients experienced
      serious AEs (SAEs), of which hallucination was determined to be a treatment
      related SAE. There were no other significant safety findings. No new safety
      signals for ropinirole were identified. CONCLUSION: The safety profile of
      ropinirole was consistent with the preceding DB study and also with the
      established safety profile for ropinirole. Results support the long-term use of
      ropinirole PR as an adjunctive to levodopa in Chinese patients with advanced PD.
      ClinicalTrials.gov identifier: NCT 1536574.

PMID- 25586299
TI  - Factors associated with over-serving at drinking establishments.
AB  - AIMS: To address characteristics of drinking establishments, bartenders and
      patrons that may affect the likelihood of over-serving. DESIGN: A systematic
      examination of 425 purchase attempts with pseudo-intoxicated patrons enacting
      scripts that, according to the law, should lead to the denial of alcohol sales.
      SETTING AND PARTICIPANTS: Drinking establishments in the three largest cities in
      Norway (Trondheim, Bergen and Oslo) were visited by male and female actors aged
      20-30 years on weekend nights, with a total of 425 purchase items. MEASUREMENTS:
      Over-serving was recorded when the pseudo-intoxicated patron was served alcohol.
      Characteristics of the drinking establishment, the bartender and the pseudo
      intoxicated patron were recorded systematically. RESULTS: Pseudo-intoxicated
      patrons were served in 347 of 425 purchase attempts (82%). In bivariate analyses,
      the over-serving rate increased with venue characteristics, music/noise level and
      intoxication level among patrons. These factors were intercorrelated and
      correlated with poor lighting. The over-serving rate was also higher when the
      pseudo-intoxicated patron was female and when the purchase attempt occurred after
      midnight. In multi-variate analyses, two factors increased the likelihood of over
      serving significantly: a high problematic bar indicator score (poor lighting,
      high music/noise level and high intoxication level among patrons) [adjusted odds
      ratio (OR) = 3.5, 95% confidence interval (CI) = 1.9, 6.4] and female gender of
      pseudo-intoxicated patrons (adjusted OR = 2.6, 95% CI = 1.4, 4.7). The rate of
      over-serving was 95% when both risk factors were present and 67% when both
      factors were absent. CONCLUSIONS: In urban settings in Norway, it is likely that
      over-serving occurs frequently, and is increased by the risk factors of poor
      lighting, loud music and high intoxication level among patrons.

PMID- 25586300
TI  - Three-dimensional reconstruction of deferent ducts papillae in urogenital duct
      system of the male rat.
AB  - BACKGROUND: The rodent ejaculatory ducts penetrate the male accessory sex gland
      complex and open into the urethra, anatomically similar to humans. Although the
      deferent ducts papillae in rodents have been described at the distal end of
      deferent ducts, they are absent in humans, and their detailed morphology has been
      unclear. METHODS: The detailed anatomical structures of the distal end of the
      deferent ducts of rats were investigated by the computer assisted three
      dimensional reconstruction analysis using serial sections of the male accessory
      sex gland complexes in rats. RESULTS: The present study revealed that a pair of
      deferent ducts enters the ventral side of the male accessory sex gland complex,
      runs caudally parallel to the urethra, and then exits at about midsection of the
      dorso-lateral lobe of prostate. They are composed of mammilliform papillae,
      called the deferent duct papillae, which dorso-laterally protrude into the duct
      lumen from intra-ventral portion of the main duct of ampullary gland. The
      internal surface of the deferent ducts papillae is composed of ciliated columnar
      epithelium continuous from the deferent ducts, while their external surface is
      composed of the columnar secretory epithelium of the ampullary glands. Sphincter
      muscles were not observed in the deferent ducts papillae, while their lamina
      propria were occupied by many arterial or venous capillaries. CONCLUSIONS: The
      deferent ducts of rat terminated at the deferent ducts papillae that located at
      the main duct of ampullary glands that drained into the urethra. The deferent
      ducts papillae might be controlled by the expansion/contraction of well-developed
      papillary mucosal capillary vessels.

PMID- 25586301
TI  - Structure of the terminal PCP domain of the non-ribosomal peptide synthetase in
      teicoplanin biosynthesis.
AB  - The biosynthesis of the glycopeptide antibiotics, of which teicoplanin and
      vancomycin are representative members, relies on the combination of non-ribosomal
      peptide synthesis and modification of the peptide by cytochrome P450 (Oxy)
      enzymes while the peptide remains bound to the peptide synthesis machinery. We
      have structurally characterized the final peptidyl carrier protein domain of the
      teicoplanin non-ribosomal peptide synthetase machinery: this domain is believed
      to mediate the interactions with tailoring Oxy enzymes in addition to its
      function as a shuttle for intermediates between multiple non-ribosomal peptide
      synthetase domains. Using solution state NMR, we have determined structures of
      this PCP domain in two states, the apo and the post-translationally modified holo
      state, both of which conform to a four-helix bundle assembly. The structures
      exhibit the same general fold as the majority of known carrier protein
      structures, in spite of the complex biosynthetic role that PCP domains from the
      final non-ribosomal peptide synthetase module must play in glycopeptide
      antibiotic biosynthesis. These structures thus support the hypothesis that it is
      subtle rearrangements, rather than dramatic conformational changes, which govern
      carrier protein interactions and selectivity during non-ribosomal peptide
      synthesis.

PMID- 25586302
TI  - Probing the electron states and metal-insulator transition mechanisms in
      molybdenum disulphide vertical heterostructures.
AB  - The metal-insulator transition is one of the remarkable electrical properties of
      atomically thin molybdenum disulphide. Although the theory of electron-electron
      interactions has been used in modelling the metal-insulator transition in
      molybdenum disulphide, the underlying mechanism and detailed transition process
      still remain largely unexplored. Here we demonstrate that the vertical metal
      insulator-semiconductor heterostructures built from atomically thin molybdenum
      disulphide are ideal capacitor structures for probing the electron states. The
      vertical configuration offers the added advantage of eliminating the influence of
      large impedance at the band tails and allows the observation of fully excited
      electron states near the surface of molybdenum disulphide over a wide excitation
      frequency and temperature range. By combining capacitance and transport
      measurements, we have observed a percolation-type metal-insulator transition,
      driven by density inhomogeneities of electron states, in monolayer and multilayer
      molybdenum disulphide. In addition, the valence band of thin molybdenum
      disulphide layers and their intrinsic properties are accessed. 

PMID- 25586303
TI  - Fibromyalgia Flares: A Qualitative Analysis.
AB  - OBJECTIVE: Patients with fibromyalgia report periods of symptom exacerbation,
      colloquially referred to as "flares" and despite clinical observation of flares,
      no research has purposefully evaluated the presence and characteristics of flares
      in fibromyalgia. The purpose of this qualitative study was to describe
      fibromyalgia flares in a sample of patients with fibromyalgia. METHODS: Using
      seven open-ended questions, patients were asked to describe how they perceived
      fibromyalgia flares and triggers and alleviating factors associated with flares.
      Patients were also asked to describe how a flare differs from their typical
      fibromyalgia symptoms and how they cope with fibromyalgia flares. Content
      analysis was used to analyze the text. RESULTS: A total of 44 participants
      completed the survey. Responses to the seven open-ended questions revealed three
      main content areas: causes of flares, flare symptoms, and dealing with a flare.
      Participants identified stress, overdoing it, poor sleep, and weather changes as
      primary causes of flares. Symptoms characteristic of flares included flu-like
      body aches/exhaustion, pain, fatigue, and variety of other symptoms. Participants
      reported using medical treatments, rest, activity and stress avoidance, and
      waiting it out to cope with flares. CONCLUSIONS: Our results demonstrate that
      periods of symptom exacerbation (i.e., flares) are commonly experienced by
      patients with fibromyalgia and symptoms of flares can be differentiated from
      every day or typical symptoms of fibromyalgia. Our study is the first of its kind
      to qualitatively explore characteristics, causes, and management strategies of
      fibromyalgia flares. Future studies are needed to quantitatively characterize
      fibromyalgia flares and evaluate mechanisms of flares.

PMID- 25586304
TI  - Genistein exerts growth inhibition on human osteosarcoma MG-63 cells via
      PPARgamma pathway.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) is emerging as
      an important regulator in various metabolic processes of cancer. Genistein, as a
      major isoflavonoid isolated from dietary soybean, possesses a wide variety of
      biological activities, particularly, in cancer prevention. However, the
      mechanisms by which genistein elicits its growth inhibiting effects in
      osteosarcoma (OS) MG-63 cells have not been extensively elucidated. MG-63 cells
      were treated for 2 days with various concentrations of genistein and/or GW9662 (a
      selective antagonist of PPARgamma). The effect of different drugs on cell
      viability was determined by Cell Counting Kit-8 (CCK-8). The assay of cell
      proliferation was performed using 5-ethynyl-2'-deoxyuridine (EdU). The changes of
      apoptosis and cell cycle progression were detected by flow cytometry experiments.
      The protein expression of PPARgamma pathway (PPARgamma, PTEN, BCL-2, Survivin,
      P21WAF1/CIP1 and Cyclin B1) was determined by western blot analysis. The
      expression of PPARgamma and PTEN mRNA was detected by real-time quantitative RT
      PCR analysis. We report that genistein caused OS cell growth inhibition. We found
      that the PPARgamma expression in OS cells increased after genistein treatment.
      Further studies on the mechanisms of genistein revealed a series of cell growth
      changes related to the PPARgamma pathway; while cell cycle changes can be
      reversed by GW9662. Genistein plays an important role in preventing OS cell
      growth, which can impede the OS cell cycle as a non-toxic activator of PPARgamma,
      providing novel insights into the mechanisms of the therapeutic activities of
      genistein.

PMID- 25586305
TI  - Identification of a Ly-6 superfamily gene expressed in lateral line neuromasts in
      zebrafish.
AB  - Lymphocyte antigen-6 (Ly-6) superfamily members have been identified in
      zebrafish, but the expression and function of these Ly-6 genes remain largely
      unknown. Posterior lateral line (pLL) system is produced by migrating pLL
      primordium (pLLp). Chemokine signaling, Notch, Wnt, and fibroblast growth factor
      (FGF) signaling regulate migration of pLLp cells and formation of neuromasts.
      However, the mechanism of neuromast deposition remains to be explored.
      Identification of novel genes expressed in pLLp will certainly help the study of
      such a process. Here we identified a Ly-6 gene called neuromast-expressed gpi
      anchored lymphocyte antigen-6 (negaly6), which was specifically expressed in
      neuromast. Quantitative real-time PCR (qRT-PCR) analysis showed that negaly6
      started to be expressed at 24 hpf, and whole-mount in situ hybridization analysis
      indicated that negaly6 was highly expressed in the trailing zone of pLLp and
      mature neuromast. Furthermore, negaly6 expression was inhibited by FGF signaling
      antagonist but not by Wnt signaling agonist or antagonist. Collectively, these
      data indicate that negaly6 may be associated with the regulation of neuromast
      deposition via FGF signaling pathway. 

PMID- 25586306
TI  - Microbiological and physicochemical analysis of pumpkin juice fermentation by the
      basidiomycetous fungus Ganoderma lucidum.
AB  - A new protocol for processing of pumpkin juice was set up which included
      fermentation by the basidiomycete Ganoderma lucidum at 28  degrees C for 7 d. The
      growth curve of G. lucidum in pumpkin juice was successfully (R(2)  = 0.99)
      fitted by a 4-parameter logistic model and the ideal highest biomass was
      estimated to be 4.79 g/L. G. lucidum was found to have a significant
      acidification effect on pumpkin juice. The lowest pH (4.05 +/- 0.05) and highest
      total titratable acidity (14.31 +/- 0.16 mL 0.1 M NaOH/100 mL) were found on the
      4th day during fermentation. Sugars in pumpkin juice fermented with G. lucidum
      showed a significant decrease, especially glucose and fructose. On the contrary,
      the release of exo-polysaccharides and free amino acids greatly enriched the
      pumpkin juice. The variation of color index and viscosity also mirrored the above
      behavior. Based on headspace solid phase microextraction and gas chromatography
      mass spectrometry, 68 volatile compounds were identified, including 17 esters, 14
      alcohols, 13 phenyl compounds, 11 aldehydes, 8 ketones, 3 acids, 1 furan, and 1
      benzothiazole. The pumpkin juices fermented for different days were markedly
      differentiated with principal component analysis and the fermentation process was
      tentatively divided into 3 periods: the booming (from the 1st to 4th day), steady
      (from the 5th to 6th day), and decline (the 7th day) period. 

PMID- 25586307
TI  - A molecular nematic liquid crystalline material for high-performance organic
      photovoltaics.
AB  - Solution-processed organic photovoltaic cells (OPVs) hold great promise to enable
      roll-to-roll printing of environmentally friendly, mechanically flexible and cost
      effective photovoltaic devices. Nevertheless, many high-performing systems show
      best power conversion efficiencies (PCEs) with a thin active layer (thickness is
      ~100 nm) that is difficult to translate to roll-to-roll processing with high
      reproducibility. Here we report a new molecular donor, benzodithiophene
      terthiophene rhodanine (BTR), which exhibits good processability, nematic liquid
      crystalline behaviour and excellent optoelectronic properties. A maximum PCE of
      9.3% is achieved under AM 1.5G solar irradiation, with fill factor reaching 77%,
      rarely achieved in solution-processed OPVs. Particularly promising is the fact
      that BTR-based devices with active layer thicknesses up to 400 nm can still
      afford high fill factor of ~70% and high PCE of ~8%. Together, the results
      suggest, with better device architectures for longer device lifetime, BTR is an
      ideal candidate for mass production of OPVs.

PMID- 25586308
TI  - Yu Ping Feng San, an Ancient Chinese Herbal Decoction, Induces Gene Expression of
      Anti-viral Proteins and Inhibits Neuraminidase Activity.
AB  - Yu Ping Feng San (YPFS), a Chinese herbal decoction comprised of Astragali Radix
      (Huangqi), Atractylodis Macrocephalae Rhizoma (Baizhu) and Saposhnikoviae Radix
      (Fangfeng), has been used clinically for colds and flus; however, the action
      mechanism of which is not known. Previously, we had demonstrated that YPFS could
      modulate inflammatory response and phagocytosis in exerting anti-viral and anti
      bacterial effects. Here, we further evaluated the bioactivities of YPFS in gene
      expression regulated by interferon (IFN) signaling and neuraminidase activity of
      influenza virus A. Application of YPFS onto cultured murine macrophages, the
      expressions of mRNAs encoding ribonuclease L (RNaseL), myxovirus (influenza
      virus) resistance 2 (Mx2), protein kinase R (PKR) and IFN-stimulated gene 15
      (ISG15) were induced from 2 to 30 folds in dose-dependent manners. In parallel,
      the transcriptional activity of IFN-stimulated response element (ISRE), an up
      stream regulator of the above anti-viral proteins, was also triggered by YPFS
      treatment. Conversely, YPFS was found to suppress the neuraminidase activity of
      influenza virus A in cultured epithelial cells, thereby preventing the viral
      release and spreading. Taken together, YPFS exerted anti-bacterial and anti-viral
      effects in innate immunity.

PMID- 25586310
TI  - Developmental effects of economic and educational change: cognitive
      representation in three generations across 43 years in a Maya community.
AB  - We studied the implications of social change for cognitive development in a Maya
      community in Chiapas, Mexico, over 43 years. The same procedures were used to
      collect data in 1969-1970, 1991, and 2012-once in each generation. The goal was
      to understand the implications of weaving, schooling and participation in a
      commercial economy for the development of visual pattern representation. In 2012,
      our participants consisted of 133 boys and girls descended from participants in
      the prior two generations. Procedures consisted of placing colored sticks in a
      wooden frame to make striped patterns, some familiar (Zinacantec woven patterns)
      and some novel (created by the investigators). Following Greenfield (2009), we
      hypothesised that the development of commerce and the expansion of formal
      schooling would influence children's representations. Her theory postulates that
      these factors move human development towards cognitive abstraction and skill in
      dealing with novelty. Furthermore, the theory posits that whatever
      sociodemographic variable is changing most rapidly functions as the primary motor
      for developmental change. From 1969 to 1991, the rapid development of a
      commercial economy drove visual representation in the hypothesised directions.
      From 1991 to 2012, the rapid expansion of schooling drove visual representation
      in the hypothesised directions. 

PMID- 25586311
TI  - Scrub typhus: audit of an outbreak.
AB  - OBJECTIVES: To document the epidemiological, clinical and laboratory profile of
      all children with scrub typhus at a tertiary care centre in Chennai between
      September 2010 and June 2011. METHODS: The case records of all children admitted
      and diagnosed with scrub typhus between September 2010 and June 2011 were
      analysed to look for salient clinical and laboratory parameters. RESULTS: During
      the study period, 52 children were admitted with scrub typhus in the authors'
      hospital. The presenting complaints included fever in all cases. Other symptoms
      included swelling of legs (50 %) and vomiting (45 %). 13 % presented with CNS
      symptoms. The commonest physical findings included eschar (67 %), hepatomegaly
      (94 %), splenomegaly (73 %) and third spacing (67 %). Salient lab parameters
      included packed cell volume (PCV) <30 (48 %), leucocytosis (56 %), positive C
      reactive protein (CRP) (92 %), hypoalbuminemia (79 %). Common complications
      included acute kidney injury (10 %) and peripheral gangrene (4 %). There was no
      mortality in the present case series. CONCLUSIONS: The clinical profile of
      children with scrub typhus in a tertiary care centre is reported. Eschar and
      hepatosplenomegaly with a high CRP value is helpful in diagnosis. All patients
      responded well to the treatment.

PMID- 25586312
TI  - Selective aerobic oxidation of HMF to 2,5-diformylfuran on covalent triazine
      frameworks-supported Ru catalysts.
AB  - The selective aerobic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5
      diformylfuran has been performed under mild conditions at 80  degrees C and 20
      bar of synthetic air in methyl t-butyl ether. Ru clusters supported on covalent
      triazine frameworks (CTFs) allowed excellent selectivity and superior catalytic
      activity compared to other support materials such as activated carbon, gamma-Al2
      O3 , hydrotalcite, or MgO. CTFs with varying pore size, specific surface area,
      and N content could be prepared from different monomers. The structural
      properties of the CTF materials influence the catalytic activity of Ru/CTF
      significantly in the aerobic oxidation of HMF, which emphasizes the superior
      activity of mesoporous CTFs. Recycling of the catalysts is challenging, but
      promising methods to maintain high catalytic activity were developed that
      facilitate only minor deactivation in five consecutive recycling experiments. 

PMID- 25586314
TI  - International Society for Plant Molecular Farming: 1st Conference, Berlin-Dahlem,
      Germany, 17th-19th June 2014.

PMID- 25586313
TI  - Current status of fish-borne zoonotic trematode infections in Gia Vien district,
      Ninh Binh province, Vietnam.
AB  - BACKGROUND: Ninh Binh province is known as an endemic area of fish-borne zoonotic
      trematode (FZT) transmission in Vietnam. A cross-sectional study was conducted in
      Gia Minh and Gia Thinh communes of Gia Vien district, Ninh Binh province to
      investigate the infections with different stages of FZT in various host species.
      METHODS: Faecal samples from 1,857 humans were examined for trematode eggs using
      the Kato-Katz method, while faecal samples from 104 dogs, 100 cats, and 100 pigs
      were examined using the Formalin-ethyl acetate concentration technique (FECT). A
      total of 483 specimens of freshwater fish, representing 9 species, were examined
      for metacercariae using the artificial digestion method. Three methods of
      cercarial detection (shedding, crushing and cutting) were applied for examination
      of 3,972 specimens of freshwater snails, representing 7 species. All relevant
      data e.g. location, sex, age group, animal species, and habitat were recorded for
      statistical analyses. RESULTS: Helminth eggs were found in 65.5% of the human
      faecal samples, including 20.5% of faecal samples containing small trematode
      eggs. Infection with small trematodes differed among communes, age groups and
      sexes. Eggs of small trematodes were found in 32.7% of faecal samples from dogs,
      49.0% from cats and 13.0% from pigs. The difference in prevalences and
      intensities were significant among species of animals but did not differ between
      the two communes. All fish species were infected with FZT, with an average
      prevalence of 56.1% and a mean intensity of 33.245 metacercariae per gram.
      Prevalence and intensity in fish differed significantly among cummunes and fish
      groups. Six species of zoonotic trematodes were identified. Metacercariae of the
      small liver fluke, Clonorchis sinensis, was only found in Hemiculter leucisculus.
      A total of 9 specimens from two snail species, Melanoides tuberculata and
      Bithynia fuchsiana, were infected with trematodes and four cercarial types were
      detected in the study sites. CONCLUSIONS: We conclude that Gia Minh and Gia Thinh
      communes are continuing to be hot-spot endemic areas of FZT and other helminths
      infections where the habit of eating raw fish by the local people is still
      present.

PMID- 25586315
TI  - Engineering temporal accumulation of a low recalcitrance polysaccharide leads to
      increased C6 sugar content in plant cell walls.
AB  - Reduced cell wall recalcitrance and increased C6 monosaccharide content are
      desirable traits for future biofuel crops, as long as these biomass modifications
      do not significantly alter normal growth and development. Mixed-linkage glucan
      (MLG), a cell wall polysaccharide only present in grasses and related species
      among flowering plants, is comprised of glucose monomers linked by both beta-1,3
      and beta-1,4 bonds. Previous data have shown that constitutive production of MLG
      in barley (Hordeum vulgare) severely compromises growth and development. Here, we
      used spatio-temporal strategies to engineer Arabidopsis thaliana plants to
      accumulate significant amounts of MLG in the cell wall by expressing the rice
      CslF6 MLG synthase using secondary cell wall and senescence-associated promoters.
      Results using secondary wall promoters were suboptimal. When the rice MLG
      synthase was expressed under the control of a senescence-associated promoter, we
      obtained up to four times more glucose in the matrix cell wall fraction and up to
      a 42% increase in saccharification compared to control lines. Importantly, these
      plants grew and developed normally. The induction of MLG deposition at senescence
      correlated with an increase of gluconic acid in cell wall extracts of transgenic
      plants in contrast to the other approaches presented in this study. MLG produced
      in Arabidopsis has an altered structure compared to the grass glucan, which
      likely affects its solubility, while its molecular size is unaffected. The
      induction of cell wall polysaccharide biosynthesis in senescing tissues offers a
      novel engineering alternative to enhance cell wall properties of lignocellulosic
      biofuel crops. 

PMID- 25586316
TI  - A modified prediction model for VBAC, in a European population.
AB  - OBJECTIVE: The first aim of the study is to validate the Grobman's Nomogram on
      Italian population, and then to include other variables with the purpose to
      increase the accuracy of the Nomogram. METHODS: This is a multicenter study in
      which eligible subjects were pregnant women reaching term having one prior
      cesarean section (CS) and then choosing for a trial of labor. Multivariate
      logistic regression model have been performed, and then the predicted percentages
      of vaginal delivery (VD) success were divided into 10 groups and compared with
      the observed ones. RESULTS: Among 1161 women, 1100 were enrolled, of which 857
      (77.9%) delivered vaginally. At the multivariate logistic regression, the
      variables predicting vaginal birth after cesarean (VBAC) in the validation were
      maternal age (p < 0.001), maternal body mass index (p = 0.007), having had a VD
      (p = 0.008) and recurring indication for CS (p < 0.001). By adding the two new
      variables in the proposed model, was reached the significance of "African
      ethnicity" (p = 0.037) and especially "years of education" (p = 0.032).
      CONCLUSIONS: The Grobman's Nomogram seems to be applicable to Italian population
      too, even if with less accuracy than in the US population. The addition of the
      level of maternal education increases the accuracy of the model, underlining the
      importance of the social context in the choice of VBAC.

PMID- 25586317
TI  - The investigation of hereditary and acquired thrombophilia risk factors in the
      development of complications in pregnancy in Croatian women.
AB  - OBJECTIVES: To investigate the genetic and acquired thrombophilic risk factors in
      pregnancy-associated complications and venous thromboembolism (VTE) and evaluate
      the association between particular thrombophilic risk factors and thromboembolic
      complications. METHODS: In this study, pregnant women with pregnancy
      complications and VTE (N = 101) were the study group, and the control group were
      women with normal pregnancy (N = 102). All women underwent testing for factor V
      Leiden mutation (FVL), mutation of the coagulation factors II (FII20210),
      methylenetetrahydrofolate reductase (MTHFR), plasminogen activator inhibitor-1,
      antithrombin III (ATIII), protein C (PC) and protein S, lupus anticoagulant (LAC)
      antibodies, anticardiolipin antibodies and anti-beta-2-glycoprotein-1. RESULTS:
      In this study group, mutations of the FVL was 15.8% (16/101), FII20210 5.9%
      (6/101) and the MTHFR at locus 677 was TT in 19.8% (20/101). Deficiency of ATIII
      and PC were rare: 3.0% and 1.0%, respectively. LAC were significantly higher in
      the study group than in the control group: 32.7% versus 3.9%; p < 0.0005.
      Pregnant women with VTE have been more frequent for FVL (41.7%; p < 0.005), PC
      deficiency (25.0%; p < 0.005) and LAC (33.3%; p < 0.005). Combination of FVL and
      MTHFR mutation was related to the risk of recurrent fetal death and habitual
      abortion. CONCLUSION: The inherited and the acquired thrombophilic risk factors
      were found to be up to 10 times more common in the study group than in the
      control group.

PMID- 25586318
TI  - Bacillus Calmette-Guerin vaccination: a novel therapeutic approach to preventing
      hyperoxic lung injury.
AB  - OBJECTIVE: A growing body of evidence suggests that vaccinations play a role in
      the normal maturation of the immune system and in both the development and
      balance of immune regulatory pathways that can impact health later in life. This
      study aimed to evaluate the effects of Bacillus Calmette-Guerin (BCG) vaccine on
      the hyperoxia-induced neonatal rat lung injury. METHODS: Four groups were defined
      as hyperoxia-exposed BCG-vaccinated, hyperoxia-exposed placebo, room air-exposed
      control and room air-exposed BCG-vaccinated group. The validity of the hyperoxia
      induced lung injury model used in this study was confirmed by histological and
      immunohistochemical test. Gene expression related with cytokine and growth factor
      was evaluated by real-time reverse transcription polymerase chain reaction.
      RESULT: The mean alveolar surface area and quantification of secondary crest
      formation in the oxygen-exposed placebo group was significantly lower than that
      of the oxygen-exposed BCG-vaccinated group. Compared to the oxygen-exposed
      placebo group, the oxygen-exposed BCG-vaccinated group showed a significantly
      decreased alveolar septal fibrosis and smooth muscle actin expression. The
      expression of genes VEGF, FGF-BP1, IL-13, and NFkappaB1 (p50) in the lungs of the
      hyperoxia-exposed BCG-vaccinated group was significantly higher than that of the
      hyperoxia-exposed placebo group. CONCLUSION: Results suggest that BCG vaccination
      can protect against neonatal hyperoxic lung injury. These benefits may be
      interpreted to coincide with its immunomodulatory effects on pro-inflammatory and
      anti-inflammatory cytokine balance and expression of growth factors.

PMID- 25586319
TI  - Does the interval since vaginal delivery influence the chance of vaginal birth
      after cesarean?
AB  - OBJECTIVE: To examine the association between interval since vaginal delivery and
      vaginal birth after cesarean (VBAC). METHODS: Women with one prior low transverse
      cesarean and a prior vaginal delivery undergoing a trial of labor after cesarean
      at term were included in this cohort study. Multivariable analyses were performed
      to determine whether length of time since prior vaginal delivery was
      independently associated with VBAC and, if so, whether its inclusion enhanced the
      predictive capacity of previously published models. RESULTS: Of the 5628 women
      included, 4901 (87%) achieved a VBAC. Each additional year since vaginal delivery
      decreased the odds of VBAC by 11% (95% CI: 10-13%). When added to an existing
      predictive model that included only factors available at early prenatal care,
      interval since vaginal delivery marginally improved the model's predictive
      ability (area under the curve [AUC] 0.73 versus 0.71, p < 0.01). When added to a
      model that included factors available proximate to the time of delivery, the
      addition of interval since vaginal delivery did not change the AUC (0.76 versus
      0.75, p = 0.08). CONCLUSIONS: A longer interval since vaginal delivery is
      associated with a decreased odd of VBAC. However, the addition of this interval
      to VBAC prediction models does not substantively improve their predictive
      ability.

PMID- 25586320
TI  - To study prevalence of persistent pulmonary hypertension in newborn with meconium
      aspiration syndrome in western Rajasthan, India: a prospective observational
      study.
AB  - AIM: To study the prevalence of persistent pulmonary hypertension (PPHN) in
      newborn with meconium aspiration syndrome (MAS) in western Rajasthan, India.
      MATERIAL AND METHODS: Hundred full-term newborns who had features of MAS at birth
      were included in this survey and were evaluated for PPHN using laboratory
      investigations, including pulse oximetry, ABG, chest X-ray, ECG and 2D color
      echocardiography. RESULTS: Nineteen neonates showed PPHN, of them 16 had a shunt
      reversal at PFO level and the rest at PDA level. Most of these newborns were
      delivered by emergency cesarean section and were unplanned. A majority of
      neonates of PPHN (84.21%) were diagnosed within 48 h of life and 73.69% had
      Downey's score more than 6. Neonates of PPHN had mean PH 7.21 +/- 0.07, mean PCO2
      53.73 +/- 6.8, mean PaO2 61.10 +/- 10.61 and mean PaO2/FiO2 144.03 +/- 46.31.
      CONCLUSIONS: PPHN is a genuine problem in MAS-born neonates and is commonly seen
      in neonates born by unplanned and unmonitored delivery, and the prevalence of
      PPHN can be reduced by providing good antenatal care, regular follow up of high
      risk pregnancy. 2D echocardiography is an important point of care in the
      diagnosis of PPHN in nursery and should be promoted in nurseries of developing
      countries as being engaged in developed countries for more reliable treatment.

PMID- 25586322
TI  - [Case management studies for individuals 65 years and older in Germany:
      Systematic review of the currently published state of research].
AB  - BACKGROUND: The aim of this systematic review was to provide an overview on the
      current state of published research on case management (CM) according to the
      definition of the German Association of Care and Case Management (DGCC) for
      individuals 65 years and older in Germany. MATERIAL AND METHODS: A systematic
      literature search was carried out for CM studies according to the DGCC in Germany
      since 2000 including individuals aged 65 years and older. RESULTS: Of the 249
      abstracts retrieved a total of 14 evaluation and intervention studies of 10
      different projects fulfilled the inclusion criteria. According to the results of
      the five evaluation studies, CM was feasible and barriers to implementation as
      well as satisfaction and positive effects of CM were described. The quality and
      outcome criteria of the intervention studies were heterogeneous. The results of
      the intervention studies can be interpreted as CM having positive effects on, for
      example hospital admissions and mortality. CONCLUSION: Only few and qualitatively
      heterogeneous studies are currently available on the intervention effects of CM
      in Germany among this age group. So far robust scientific evidence of this method
      in Germany seems to be lacking.

PMID- 25586323
TI  - [Cognitive assessment for immigrants].
AB  - In recent years, an increasing number of clients visiting the Gerontopsychiatric
      Center for Psychosocial Services in Vienna are immigrants who grew up in
      countries other than Austria. What has proven to work best for neuropsychological
      examination is translation--interpretation performed by their family relatives.
      For the testing procedure, success has been achieved with the Quick Clock Three
      Word Combination, the Mini-Mental State Examination and the 10-Word Test with
      Memorizing Aid. For those without the benefit of an education, the transcultural,
      non-verbal EASY test is recommended. Although immigrants, when first examined in
      the Center, are as a rule younger than clients who grew up in Austria, they come
      to the Center in a clearly more advanced state of dementia.

PMID- 25586321
TI  - [Vitamin B12 deficiency in the elderly].
AB  - The prevalence of vitamin B12 deficiency increases with age. Patients with
      dementia and spouses of patients with dementia are at special risk for the
      development of vitamin B12 deficiency. In a normal diet this vitamin is present
      only in animal source foods; therefore, vegans frequently develop vitamin B12
      deficiency if not using supplements or foods fortified with cobalamin. Apart from
      dementia, most of these manifestations are completely reversible under correct
      therapy; therefore it is crucial to identify and to treat even atypical
      presentations of vitamin B12 deficiency as early as possible. This article deals
      with the physiology and pathophysiology of vitamin B12 metabolism. A practice
      oriented algorithm which also considers health economic aspects for a rational
      laboratory diagnosis of vitamin B12 deficiency is presented. In cases with severe
      neurological symptoms, therapy should be parenteral, especially initially. For
      parenteral treatment, hydroxocobalamin is the drug of choice.

PMID- 25586324
TI  - [Timed up and go test for fingers in the form of the 20 cents test. Psychometric
      criteria of a simple performance test of fine motor skills].
AB  - BACKGROUND: Although many activities depend on intact fine motor skills no
      standardized assessment has been broadly established. The 20 cents test (20-C-T)
      was developed in 2009 and takes less than 5 mins. The quality criteria were
      investigated within the framework of this study. PATIENTS AND METHODS: A total of
      300 geriatric patients participated in the study. The classification of
      occupational therapists based on standardized anamnesis and clinical examination
      served as the gold standard. Physiotherapists blinded to the study particulars
      applied the 20-C-T. RESULTS: Every fourth patient suffered from deficits in fine
      motor skills relevant to everyday life. The 20-C-T correlated with the clinical
      severity level and was also feasible for patients with intermediate impairment of
      cognition or vision. Handedness, age and sex were without significant influence.
      Intrarater and interrater reliability were good. CONCLUSION: Standardized testing
      of fine motor skills should be included in geriatric screening and basic
      assessment. The quality criteria of the 20-C-T show that it can be used for this
      purpose. Further diagnostic steps are recommended whenever a geriatric patient
      needs more than 40 s for the task.

PMID- 25586325
TI  - A surrogate-primary replacement algorithm for response-adaptive randomization in
      stroke clinical trials.
AB  - Response-adaptive randomization (RAR) offers clinical investigators benefit by
      modifying the treatment allocation probabilities to optimize the ethical,
      operational, or statistical performance of the trial. Delayed primary outcomes
      and their effect on RAR have been studied in the literature; however, the
      incorporation of surrogate outcomes has not been fully addressed. We explore the
      benefits and limitations of surrogate outcome utilization in RAR in the context
      of acute stroke clinical trials. We propose a novel surrogate-primary (S-P)
      replacement algorithm where a patient's surrogate outcome is used in the RAR
      algorithm only until their primary outcome becomes available to replace it.
      Computer simulations investigate the effect of both the delay in obtaining the
      primary outcome and the underlying surrogate and primary outcome distributional
      discrepancies on complete randomization, standard RAR and the S-P replacement
      algorithm methods. Results show that when the primary outcome is delayed, the S-P
      replacement algorithm reduces the variability of the treatment allocation
      probabilities and achieves stabilization sooner. Additionally, the S-P
      replacement algorithm benefit proved to be robust in that it preserved power and
      reduced the expected number of failures across a variety of scenarios.

PMID- 25586327
TI  - Statistical interactions and Bayes estimation of log odds in case-control
      studies.
AB  - This paper is concerned with the estimation of the logarithm of disease odds (log
      odds) when evaluating two risk factors, whether or not interactions are present.
      Statisticians define interaction as a departure from an additive model on a
      certain scale of measurement of the outcome. Certain interactions, known as
      removable interactions, may be eliminated by fitting an additive model under an
      invertible transformation of the outcome. This can potentially provide more
      precise estimates of log odds than fitting a model with interaction terms. In
      practice, we may also encounter nonremovable interactions. The model must then
      include interaction terms, regardless of the choice of the scale of the outcome.
      However, in practical settings, we do not know at the outset whether an
      interaction exists, and if so whether it is removable or nonremovable. Rather
      than trying to decide on significance levels to test for the existence of
      removable and nonremovable interactions, we develop a Bayes estimator based on a
      squared error loss function. We demonstrate the favorable bias-variance trade
      offs of our approach using simulations, and provide empirical illustrations using
      data from three published endometrial cancer case-control studies. The methods
      are implemented in an R program, and available freely at
      http://www.mskcc.org/biostatistics/~satagopj .

PMID- 25586328
TI  - Utilization of different waste proteins to create a novel PGPR-containing bio
      organic fertilizer.
AB  - High-quality bio-organic fertilizers (BIOs) cannot be produced without the
      addition of some proteins, while many waste proteins are haphazardly disposed,
      causing serious environmental pollution. In this study, several waste proteins
      were used as additives to assist with the reproduction of the functional microbe
      (Bacillus amyloliquefaciens SQR9) inoculated into matured composts to produce
      BIOs. An optimized composition of solid-state fermentation (SSF) raw materials
      was predicted by response surface methodology and experimental validation. The
      results showed that 7.61% (w/w, DW, the same below) rapeseed meal, 8.85% expanded
      feather meal, 6.47% dewatered blue algal sludge and 77.07% chicken compost
      resulted in maximum biomass of strain SQR-9 and the maximum amount of
      lipopeptides 7 days after SSF. Spectroscopy experiments showed that the inner
      material structural changes in the novel SSF differed from the control and the
      novel BIO had higher dissolved organic matter. This study offers a high value
      added utilization of waste proteins for producing economical but high-quality
      BIO. 

PMID- 25586329
TI  - Mitochondrial aquaporin-8-mediated hydrogen peroxide transport is essential for
      teleost spermatozoon motility.
AB  - Reactive oxygen species (ROS), particularly hydrogen peroxide (H2O2), cause
      oxidative cell damage and inhibit sperm function. In most oviparous fishes that
      spawn in seawater (SW), spermatozoa may be exposed to harmful ROS loads
      associated with the hyperosmotic stress of axonemal activation and ATP synthesis
      from mitochondrial oxidative phosphorylation. However, it is not known how marine
      spermatozoa can cope with the increased ROS levels to maintain flagellar
      motility. Here, we show that a marine teleost orthologue of human aquaporin-8,
      termed Aqp8b, is rapidly phosphorylated and inserted into the inner mitochondrial
      membrane of SW-activated spermatozoa, where it facilitates H2O2 efflux from this
      compartment. When Aqp8b intracellular trafficking and mitochondrial channel
      activity are immunologically blocked in activated spermatozoa, ROS levels
      accumulate in the mitochondria leading to mitochondrial membrane depolarisation,
      the reduction of ATP production, and the progressive arrest of sperm motility.
      However, the decreased sperm vitality underlying Aqp8b loss of function is fully
      reversed in the presence of a mitochondria-targeted antioxidant. These findings
      reveal a previously unknown detoxification mechanism in spermatozoa under
      hypertonic conditions, whereby mitochondrial Aqp8b-mediated H2O2 efflux permits
      fuel production and the maintenance of flagellar motility. 

PMID- 25586331
TI  - Fibrocaps for surgical hemostasis: two randomized, controlled phase II trials.
AB  - BACKGROUND: Fibrocaps, a ready-to-use, dry-powder fibrin sealant containing human
      plasma-derived thrombin and fibrinogen, is being developed as an adjunct for
      surgical hemostasis. MATERIALS AND METHODS: Safety and efficacy of Fibrocaps
      applied directly or by spray device, in combination with gelatin sponge, was
      compared with that of gelatin sponge-alone in two randomized, single-blind
      controlled trials: FC-002 US (United States) and FC-002 NL (the Netherlands). A
      total of 126 adult patients were randomized (Fibrocaps: n = 47 [FC-002 US], n =
      39 [FC-002 NL]; gelatin sponge alone: n = 23 [FC-002 US], n = 17 [FC-002 NL). One
      bleeding site was treated during a surgical procedure (n = 125). Time to
      hemostasis (primary end point) was measured, with a 28-d safety follow-up. Four
      surgical indications included hepatic resection (n = 58), spinal procedures (n =
      37), peripheral vascular procedures (n = 30), and soft tissue dissection (n = 1).
      RESULTS: Mean (standard deviation) time to hemostasis was significantly shorter
      after Fibrocaps treatment than after gelatin sponge alone (FC-002 US: 1.9 [1.3]
      versus 4.8 min [3.1], P < 0.001; FC-002 NL: 2.2 [1.3] versus 4.4 min [3.1], P =
      0.004). The incidence of hemostasis was greater after Fibrocaps compared with
      that of gelatin sponge alone within 3 min (FC-002 US: 83% versus 35%, P < 0.001;
      FC-002 NL: 77% versus 53%, P = 0.11), 5 min (94% versus 61%, P = 0.001; 95%
      versus 71%, P = 0.022), and 10 min (100% versus 78%, P = 0.003; 100% versus 82%,
      P = 0.025). Adverse events were consistent with surgical procedures performed and
      patients' underlying diseases and generally similar between treatment arms; most
      were mild or moderate in severity. Non-neutralizing antithrombin antibodies were
      detected in 5% of Fibrocaps-treated patients on day 29. CONCLUSIONS: Fibrocaps
      had good safety and efficacy profiles, supporting continuing clinical development
      as a novel fibrin sealant.

PMID- 25586332
TI  - Using negative pressure wound therapy on microskin autograft wounds.
AB  - BACKGROUND: Microskin autografts with conventional wrap and compression are used
      extensively in the treatment of skin and tissue defects. This comparative study
      aimed at investigation of the clinical application of negative pressure wound
      therapy (NPWT) in combination with microskin autografts for repair of acute and
      chronic wounds. METHODS: A prospective case-control study was performed from
      December 1, 2010-December 31, 2013 in Changhai Hospital, Shanghai. We compared a
      study group of patients received microskin autografting covered by NPWT with that
      of a control group of patients received microskin autografting covered by a
      conventional gauze. RESULTS: A total of 81 patients were in this study, 27
      patients were allocated to the study group and 54 patients to the control group.
      The study group exhibited significant low infection rate and pain score during
      removal of inner layer at first dressing change after skin grafting compared with
      those of the control group (P < 0.05). The time interval between skin grafting
      and first postoperative change was longer in the study group than that in the
      control group (P < 0.01), the study group showed a significant shorter 95% wound
      healing time (P < 0.05), and survival rate of microskin autografts in the study
      group was higher than that in the control group (P < 0.05). CONCLUSIONS: NPWT is
      beneficial for wound closure after microskin autografts, which prolongs the
      interval between skin transplantation and first postoperative dressing change,
      reduces pain during removal of inner layer dressing, increases skin graft
      survival rate, and shortens wound healing time. Therefore, NPWT can be
      recommended for repair of acute and chronic wounds with microskin autografts.

PMID- 25586330
TI  - Air pollution and mortality in Sao Paulo, Brazil: Effects of multiple pollutants
      and analysis of susceptible populations.
AB  - Health impacts of air pollution may differ depending on sex, education,
      socioeconomic status (SES), location at time of death, and other factors. In Sao
      Paulo, Brazil, questions remain regarding roles of individual and community
      characteristics. We estimate susceptibility to air pollution based on individual
      characteristics, residential SES, and location at time of death (May 1996
      December 2010). Exposures for particulate matter with an aerodynamic diameter <=
      10 MUm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide
      (CO), and ozone (O3) were estimated using ambient monitors. Time-stratified case
      crossover analysis was used with individual-level health data. Increased risk of
      non-accidental, cardiovascular, and respiratory mortality were associated with
      all pollutants (P < 0.05), except O3 and cardiovascular mortality. For non
      accidental mortality, effect estimates for those with > 11 years education were
      lower than estimates for those with 0 years education for NO2, SO2, and CO (1.66%
      (95% confidence interval: 0.23%, 3.08%); 1.51% (0.51%, 2.51%); and 2.82% (0.23%,
      5.35%), respectively). PM10 cardiovascular mortality effects were (3.74% (0.044%,
      7.30%)) lower for the high education group (> 11 years) compared with the no
      education group. Positive, significant associations between pollutants and
      mortality were observed for in-hospital deaths, but evidence of differences in
      air pollution-related mortality risk by location at time of death was not strong.

PMID- 25586333
TI  - A comparison of patients diagnosed with pulmonary embolism who are >=65 years
      with patients <65 years.
AB  - Recent studies have highlighted differences in how older patients respond to high
      risk pulmonary embolism (PE) and treatment. However, guidelines for PE risk
      stratification and treatment are not based on age, and data are lacking for older
      patients. We characterized the impact of age on clinical features, risk
      stratification, treatment, and outcomes in a sample of patients with PE in the
      emergency department. We performed an observational cohort study of 547
      consecutive patients with PE in the emergency department from 2005 to 2011 in an
      urban tertiary hospital. We used bivariate proportions and multivariable logistic
      regression to compare clinical presentation, risk category, treatment, and
      outcomes in patients >=65 years with those <65 years. The mean age was 58 +/- 17
      years, 276 (50%) were women, and 210 (38%) were >=65 years. PE was more severe in
      patients >=65 years (massive 14% vs 5%, submassive 48% vs 25%, and low risk 38%
      vs 70%, p <0.0001), with submassive PE being the most common presentation in
      patients >=65 years. However, subanalysis removing natriuretic peptides from the
      definition of submassive PE negated this finding. Treatment with parenteral
      anticoagulation (88% vs 90%, p = 0.32), thrombolytic therapy (5% vs 4%, p =
      0.87), and inferior vena cava filter (4% vs 4%, p = 0.73) were similar among age
      groups. Patients >=65 years had higher 30-day mortality (11% vs 3%, p <0.001). In
      conclusion, patients >=65 years present with more severe PE and have higher
      mortality, although treatment patterns were similar to younger patients. Age
      specific guideline definitions of submassive PE may better identify high-risk
      patients.

PMID- 25586334
TI  - Usefulness of ventricular premature complexes in asymptomatic patients <=21 years
      as predictors of poor left ventricular function.
AB  - Although ventricular premature complexes (VPCs) have been shown to correlate with
      decreased cardiac function in adults, the correlation of left ventricular (LV)
      function to VPCs in asymptomatic children remains unclear. The aim of this study
      was to determine the correlation of VPC burden with LV function in asymptomatic
      pediatric patients with structurally normal hearts. This was a retrospective
      analysis of patients aged <=21 years with echocardiograms and 24-hour Holter
      monitors with >=0.5% VPCs completed within 60 days of each other. LV fractional
      shortening (FS) was compared with VPC burden and VPC characteristics. Normal LV
      function was defined as FS >=28%. Correlation between VPC burden and LV function
      was determined by regression analysis. Wilcoxon's rank-sum test was used to
      compare LV function with VPC characteristics. This study included 123 patients
      (77 male [63%]). The median age was 11.6 years (interquartile range 5.8 to 14.3).
      The median VPC burden was 11.2% (interquartile range 4.8% to 18.9%), and median
      FS was 36% (interquartile range 33% to 38%). There was no significant correlation
      between VPC burden and LV FS (p = 0.50). The presence of uniform versus multiform
      VPCs (p = 0.29), ventricular couplets (p = 0.37), or runs of ventricular ectopy
      (p = 0.19) were not associated with a decrease in LV FS. Twenty-two patients
      (18%) had VPC burden >24%, none of which had decreased LV FS. In conclusion,
      there was no significant relation between VPC burden or VPC characteristics and
      LV systolic function in this pediatric population with structurally normal
      hearts.

PMID- 25586336
TI  - Classifications in Brief: The Hawkins Classification for Talus Fractures.

PMID- 25586335
TI  - Utility of peak creatine kinase-MB measurements in predicting myocardial infarct
      size, left ventricular dysfunction, and outcome after first anterior wall acute
      myocardial infarction (from the INFUSE-AMI trial).
AB  - Infarct size after ST-segment elevation myocardial infarction (STEMI) is
      associated with long-term clinical outcomes. However, there is insufficient
      information correlating creatine kinase-MB (CK-MB) or troponin levels to infarct
      size and infarct location in first-time occurrence of STEMI. We, therefore,
      assessed the utility of CK-MB measurements after primary percutaneous coronary
      intervention of a first anterior STEMI using bivalirudin anticoagulation in
      patients who were randomized to intralesion abciximab versus no abciximab and to
      manual thrombus aspiration versus no aspiration. Infarct size (as a percentage of
      total left ventricular [LV] mass) and LV ejection fraction (LVEF) were evaluated
      by cardiac magnetic resonance imaging at 30 days and correlated to peak CK-MB.
      Peak CK-MB (median 240 IU/L; interquartile range 126 to 414) was significantly
      associated with infarct size and with LVEF (r = 0.67, p <0.001; r = -0.56, p
      <0.001, respectively). A large infarct size (greater than or equal the median,
      defined as 17% of total LV mass) and LVEF <=40% were more common in the highest
      peak CK-MB tertile group than in the other tertiles (87.6% vs 49.5% vs 9.1%, p
      <0.001; 43.2% vs 14.0% vs 4.6%, p <0.001, respectively). Peak CK-MB of at least
      300 IU/L predicted with moderate accuracy both a large infarct size (area under
      the curve 0.88) and an LVEF <=40% (area under the curve 0.78). Furthermore, CK-MB
      was an independent predictor of 1-year major adverse cardiac events (hazard ratio
      1.42 per each additional 100 IU/L [1.20 to 1.67], p <0.001). In conclusion, CK-MB
      measurement is useful in estimating infarct size and LVEF and in predicting 1
      year clinical outcomes after primary percutaneous coronary intervention for first
      anterior STEMI.

PMID- 25586337
TI  - Current role of cabozantinib in metastatic castration-resistant prostate cancer.
AB  - Over 80% of men with castration-resistant prostate cancer have bone metastases.
      This condition can dramatically impact quality of life and is associated with
      short-term survival. Consequently, the development of bone-targeted therapies is
      a relevant topic on prostate cancer management. Hepatocyte growth factor receptor
      and vascular endothelial growth factor signaling pathways have been identified to
      play a role in prostate cancer progression and bone metastasis and are potential
      targets for therapeutic intervention. Early-phase studies have shown encouraging
      responses in bone metastases and pain control with cabozantinib, a multi-tyrosine
      kinase inhibitor targeting hepatocyte growth factor receptor and vascular
      endothelial growth factor receptor. Despite striking responses seen in some
      patients, preliminary results from a pivotal Phase III study have failed to
      produce survival benefit. This review encompasses preclinical and clinical data
      of cabozantinib in metastatic castration-resistant prostate cancer highlighting
      future research options for this agent. 

PMID- 25586338
TI  - Liminality in preregistration mental health nurse education: a review of the
      literature.
AB  - This paper provides an analysis of the anthropological concept of liminality in
      relation to undergraduate preregistration mental health nurse education, and
      considers implications both for students and nurse educators working in this
      field. A review of educational and professional literature was undertaken in
      order to clarify the concept of liminality within the context of nurse education
      to aid in understanding how nurse educators could maximise the potential of
      liminality within the mental health preregistration nursing programme, and to
      consider the relationship between liminality and the preparation of future mental
      health nursing practitioners. A survey of the findings and conclusions of the
      selected studies yielded two key areas in which the concept has an explanatory
      function: in relation to "threshold concepts" in nurse education and as a way of
      describing a stage in the development of a role and identity. Discussion of each
      of these areas points to suggestions for changes in the understanding of
      education and training for mental health nurses, particularly in the context of
      the United Kingdom. 

PMID- 25586339
TI  - Preparing students for clinical placements: The student's perspective.
AB  - Educating undergraduate nurses in the 21st century provides some very realistic
      challenges. Decreased government health budgets, increased student numbers and
      higher patient acuities have resulted in a reduction in the availability and
      quality of clinical placements. Simulated nursing practice is an innovative
      strategy designed to address these concerns. A simulation programme was designed
      for first year undergraduate nursing students to help prepare them for clinical
      placement. The aim of this research is to assess student perspectives and
      learning from the newly introduced simulation programme. This study is a
      descriptive design with Kolb's experiential theory providing a theoretical
      framework. 158 first year students taking part in a four day simulation programme
      chose to complete a questionnaire on programme completion. Students responded to
      five statements using a likert scale and categories developed and refined for the
      remaining four questions. Students reported significant learning in the areas of
      basic clinical skills and clinical documentation and collaborative care. 100% of
      students recommended the programme continue. 

PMID- 25586340
TI  - Molecular motion of donor-acceptor catenanes in water.
AB  - In this article, we use (1)H NMR spectroscopy to study the spontaneous molecular
      motion of donor-acceptor [2]catenanes in water. Our data supports the hypothesis
      that conformational motion dominantly occurs through a pirouetting mechanism,
      which involves less exposure of hydrophobic surfaces than in a rotation
      mechanism. Motion is controlled by the size of the catenane rings and the
      arrangement of the electron-deficient and electron-rich aromatic units. 

PMID- 25586341
TI  - Change in structure and ligand binding properties of hyperstable cytochrome c555
      from Aquifex aeolicus by domain swapping.
AB  - Cytochrome c555 from hyperthermophilic bacteria Aquifex aeolicus (AA cyt c555 )
      is a hyperstable protein belonging to the cyt c protein family, which possesses a
      unique long 310 -alpha-310 helix containing the heme-ligating Met61. Herein, we
      show that AA cyt c555 forms dimers by swapping the region containing the extra
      310 -alpha-310 helix and C-terminal alpha-helix. The asymmetric unit of the
      crystal of dimeric AA cyt c555 contained two dimer structures, where the
      structure of the hinge region (Val53-Lys57) was different among all four
      protomers. Dimeric AA cyt c555 dissociated to monomers at 92 +/- 1 degrees C
      according to DSC measurements, showing that the dimer was thermostable. According
      to CD measurements, the secondary structures of dimeric AA cyt c555 were
      maintained at pH 2.2-11.0. CN(-) and CO bound to dimeric AA cyt c555 in the
      ferric and ferrous states, respectively, owing to the flexibility of the hinge
      region close to Met61 in the dimer, whereas these ligands did not bind to the
      monomer under the same conditions. In addition, CN(-) and CO bound to the
      oxidized and reduced dimer at neutral pH and a wide range of pH (pH 2.2-11.0),
      respectively, in a wide range of temperature (25-85 degrees C), owing to the
      thermostability and pH tolerance of the dimer. These results show that the ligand
      binding character of hyperstable AA cyt c555 changes upon dimerization by domain
      swapping. 

PMID- 25586343
TI  - Characterization of topical film-forming systems using atomic force microscopy
      and Raman microspectroscopy.
AB  - Polymeric film-forming systems for dermal drug delivery represent an advantageous
      alternative to more conventional topically applied formulations. Their mechanical
      properties and homogeneity can be characterized with atomic force microscopy
      (AFM), using both imaging and nanoindentation modes, and Raman microspectroscopy
      mapping. Film-forming polymers, with and without a plasticizer and/or
      betamethasone 17-valerate (a representative topical drug), were dissolved in
      absolute ethanol. Polymeric films were then cast on glass slides and examined in
      ambient air using AFM imaging and Raman microspectroscopy. Using nanoindentation,
      the elastic moduli of various films were determined and found to decrease with
      increasing plasticizer content. Films with 20% w/w plasticizer had elastic moduli
      close to that of skin. AFM images showed little difference in the topography of
      the films on incorporation of plasticizer. Raman microspectroscopy maps of the
      surface of the polymeric films, with a spatial resolution of approximately 1 MUm,
      revealed homogeneous distributions of plasticizer and drug within the films. 

PMID- 25586342
TI  - The Yersinia pestis HmsCDE regulatory system is essential for blockage of the
      oriental rat flea (Xenopsylla cheopis), a classic plague vector.
AB  - The second messenger molecule cyclic diguanylate is essential for Yersinia pestis
      biofilm formation that is important for blockage-dependent plague transmission
      from fleas to mammals. Two diguanylate cyclases (DGCs) HmsT and Y3730 (HmsD) are
      responsible for biofilm formation in vitro and biofilm-dependent blockage in the
      oriental rat flea Xenopsylla cheopis respectively. Here, we have identified a
      tripartite signalling system encoded by the y3729-y3731 operon that is
      responsible for regulation of biofilm formation in different environments. We
      present genetic evidence that a putative inner membrane-anchored protein with a
      large periplasmic domain Y3729 (HmsC) inhibits HmsD DGC activity in vitro while
      an outer membrane Pal-like putative lipoprotein Y3731 (HmsE) counteracts HmsC to
      activate HmsD in the gut of X. cheopis. We propose that HmsE is a critical
      element in the transduction of environmental signal(s) required for HmsD
      dependent biofilm formation. 

PMID- 25586344
TI  - The impact of hydroquinone on acetylcholine esterase and certain human carbonic
      anhydrase isoenzymes (hCA I, II, IX, and XII).
AB  - Carbonic anhydrases (CAs) are widespread and the most studied members of a great
      family of metalloenzymes in higher vertebrates including humans. CAs were
      investigated for their inhibition of all of the catalytically active mammalian
      isozymes of the Zn(2+)-containing CA, (CA, EC 4.2.1.1). On the other hand,
      acetylcholinesterase (AChE. EC 3.1.1.7), a serine protease, is responsible for
      ACh hydrolysis and plays a fundamental role in impulse transmission by
      terminating the action of the neurotransmitter ACh at the cholinergic synapses
      and neuromuscular junction. In the present study, the inhibition effect of the
      hydroquinone (benzene-1,4-diol) on AChE activity was evaluated and effectively
      inhibited AChE with Ki of 1.22 nM. Also, hydroquinone strongly inhibited some
      human cytosolic CA isoenzymes (hCA I and II) and tumour-associated transmembrane
      isoforms (hCA IX, and XII), with Kis in the range between micromolar (415.81 MUM)
      and nanomolar (706.79 nM). The best inhibition was observed in cytosolic CA II.

PMID- 25586345
TI  - Different frequencies and effects of ABCB1 T3435C polymorphism on clinical and
      laboratory features of B cell chronic lymphocytic leukemia in Kurdish patients.
AB  - Finding the effects of gene polymorphism on cancer pathogenesis is very
      desirable. The ATP-binding cassette is involved in drug metabolism, and the
      polymorphism of this gene may be an important risk factor in B cell chronic
      lymphocytic leukemia (B-CLL) or progression and/or response to chemotherapy
      agents. For the first time, the present study was aimed to evaluate the probable
      effects of ABCB1 T3435C polymorphism on clinical and laboratory features of
      Kurdish patients with B-CLL. This descriptive analytical case-control study was
      performed on 50 B-CLL patients and 100 healthy subjects. Serum levels of beta-2
      microglobulin (B2M) and lactate dehydrogenase (LDH) and blood WBC, RBC, Plt and
      ESR were measured. The T3435C polymorphism of the ABCB1 gene was determined by
      PCR-RFLP. Concentration of serum and blood markers was significantly higher in
      the malignant group than in the benign subjects. The CC genotype had the highest
      frequency (66%) in the patient groups. There are no significant differences
      between the genotypes and type of treatment. Our results demonstrate the high
      frequency of C allele of ABCB1 T3435C in B-CLL patients with Kurdish ethnicity.
      We also show that this polymorphism has a significant risk factor in B-CLL.
      However, the effect of this polymorphism on clinical and laboratory
      characteristics of B-CLL patients was not significant.

PMID- 25586346
TI  - Transcriptome profiling of the cancer and adjacent nontumor tissues from cervical
      squamous cell carcinoma patients by RNA sequencing.
AB  - Cervical cancer is the third most common cancer and the fourth leading cause of
      cancer deaths among women in the world. The discovery of vital diagnostic and
      therapeutic markers against cervical squamous cell carcinoma (CSCC) would broaden
      our understanding on the molecular basis of CSCC. In this study, we thoroughly
      analyzed the transcriptome of CSCC and matched adjacent nontumor (ATN) tissue.
      RNA sequencing was performed to screen the differentially expressed genes (DEGs)
      of three pairs of CSCC and ATN tissues. Functional enrichment analysis was used
      to uncover the biological functions of DEGs. Protein interaction network was
      carried out to reveal interaction of DEGs. Quantitative real-time PCR was
      conducted to validate the expression of DEGs. Immunohistochemistry was used to
      detect the relationship between clinicopathological parameters of CSCC and DEGs.
      There were a total of 347 significantly common DEGs in the three paired examples,
      including 104 consistent upregulated and 148 consistent downregulated DEGs. The
      347 DEGs were categorized into 73 functional categories by Gene Ontology (GO)
      analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment
      analysis suggested six significantly signal pathways. The protein interaction
      network uncovered three important DEGs, including retinol dehydrogenase 12
      (RDH12), ubiquitin D (UBD), and serum amyloid A1 (SAA1). We found that RDH12
      expression was decreased in 74.5 % of CSCC tissues. RDH12 expression was
      negatively associated with tumor size and depth of cervical invasion. The UBD was
      overexpressed in 61.7 % of CSCC tissues and was positively related with tumor
      size and lymphatic metastasis. The SAA1 protein was overexpressed in 57.4 % of
      CSCC tissues and was positively related with clinicopathological parameters of
      tumor size, lymphatic metastasis, and depth of cervical invasion. The RDH12, UBD,
      and SAA1 genes might participate in the progression of CSCC.

PMID- 25586347
TI  - Effect of HOTAIR rs920778 polymorphism on breast cancer susceptibility and
      clinicopathologic features in a Turkish population.
AB  - Overexpression of Hox transcript antisense intergenic RNA (HOTAIR), a long non
      coding RNA (lncRNA), is associated with cancer cell proliferation, invasion,
      progression, and metastasis as well as poor survival in a variety of human
      cancers including breast cancer (BC). A common functional single nucleotide
      polymorphism (SNP) rs920778 (T -> C) in the intronic enhancer of the HOTAIR has
      been reported to influence HOTAIR expression and cancer predisposition, but the
      association of HOTAIR rs920778 polymorphism with BC susceptibility and
      clinicopathological features has yet to be investigated. We genotyped HOTAIR
      rs920778 polymorphism in 245 Turkish women including 123 BC patients and 122 age
      matched healthy controls by a real-time polymerase chain reaction (PCR) with the
      TaqMan assay. We found that the CC genotype of HOTAIR rs920778 polymorphism
      significantly increased the risk of BC in both codominant (odds ratio (OR) =
      2.12, 95 % confidence interval (CI) 1.00-4.51, P = 0.05) and recessive (OR =
      2.40, 95 % CI 1.22-4.73, P = 0.01) inheritance genetic models. Our research also
      indicated an association between the CC genotype of HOTAIR rs920778 polymorphism
      and clinicopathologic features of tumor, including advanced tumor-node-metastasis
      (TNM) stage, larger tumor size, distant metastasis, and poor histological grade
      (P < 0.05). Because our findings suggest for the first time that the CC genotype
      of HOTAIR rs920778 polymorphism might play important roles in genetic
      susceptibility to BC development and aggressiveness in a Turkish population,
      further independent studies are required to validate our findings in a larger
      series, as well as in patients of different populations.

PMID- 25586348
TI  - FBW7 increases drug sensitivity to cisplatin in human nasopharyngeal carcinoma by
      downregulating the expression of multidrug resistance-associated protein.
AB  - F-box/WD repeat-containing protein 7 (FBW7) is a member of the F-box protein
      family that regulates cell cycle progression and cell growth and differentiation.
      FBW7 also functions as a tumor suppressor. A cisplatin (CDDP)-based multidrug
      chemotherapy regimen is standard for nasopharyngeal carcinoma (NPC), but drug
      resistance is an increasing problem. Here, we evaluated the relationship between
      FBW7 and multidrug resistance-associated protein (MRP), and its correlation with
      drug resistance in NPC, and explored the mechanism underlying drug resistance to
      CDDP in this disease. We used cell viability assays, Western blotting, and small
      interfering RNA (siRNA) interference to investigate the underlying mechanism
      underlying CDDP resistance in a NPC cell line. The expression of FBW7 and MRP was
      detected by Western blotting after siRNA interference in the CDDP-resistant NPC
      cell line, CNE2-CDDP. The 3-(4 5-dimethyl-2-thiazolyl)-2 5-diphenyl-2-H
      tetrazolium bromide (MTT) assay was used to evaluate drug sensitivity of various
      types of antitumor drugs, including paclitaxel (PCX), CDDP, fluorouracil (5-FU),
      and vincristine (VCR). We found that siRNA-mediated upregulation of FBW7
      significantly increased CDDP chemosensitivity. The IC50 values of CDDP in siRNA
      FBW7-CNE2-CDDP and FBW7-CNE2-CDDP-NC cells were 2.485 +/- 0.155 and 4.867 +/-
      0.442 MUmol/mL, respectively. The IC50 values of PCX, CDDP, 5-FU, and VCR were
      significantly decreased in siRNA-FBW7-CNE2 than in FBW7-CNE2-NC (3.46 +/- 0.14
      vs. 46.21 +/- 6.03 MUmol/mL; 3.76 +/- 0.54 vs. 39.45 +/- 0.96 MUmol/mL; 2.14 +/-
      1.67 vs. 28.76 +/- 1.89 MUmol/mL; 4.43 +/- 0.89 vs. 87.90 +/- 3.45 MUmol/mL,
      respectively). The IC50 of CDDP was significantly less in siRNA-FBW7-CNE2-CDDP
      than in FBW7-CNE2-CDDP-NC. The level of FBW7 expression in CNE2 cells was
      correlated with CDDP chemosensitivity. siRNA-mediated upregulation of FBW7
      expression downregulated the expression of MRP, significantly increasing drug
      sensitivity in CNE2 cells.

PMID- 25586349
TI  - Bypassing the need for pre-sensitization of cancer cells for anticancer TRAIL
      therapy with secretion of novel cell penetrable form of Smac from hA-MSCs as
      cellular delivery vehicle.
AB  - TNF-related apoptosis inducing ligand (TRAIL) is a novel anticancer agent with
      selective apoptosis-inducing activity on cancer cells. However, many malignant
      tumors still remain unresponsive. Although cells can bypass apoptosis by
      different functions, the defect in the blocking role of second mitochondria
      derived activator of caspase (Smac) on X-linked inhibitor of apoptosis protein
      (XIAP) is known to be an important hub for immortal characteristic of malignant
      cells. Actually, XIAP is known as an apoptosis inhibitor. To date, the
      sensitization of cancerous cells to TRAIL was successfully performed with
      different protocols, mainly through blocking XIAP with Smac administration.
      However, all these sensitization methodologies need to be performed prior to
      TRAIL administration on cancerous cells which in turn limit their practical
      application in clinics. Therefore, we hypothesized that concurrent expression of
      Smac and TRAIL on human adipose-derived mesenchymal stem cells (hA-MSC-ST) could
      both sensitize and destroy cancerous cells. To this aim, we generated hA-MSC-ST,
      secreting a novel cell penetrable form of Smac and a trimeric form of TRAIL.
      Indeed, the cell penetrable form of Smac obviates the need for any pretreatment
      of cancerous cells. Our data depicted that individual overexpression of TRAIL or
      Smac in different breast cancer cell types induced limited or no apoptosis,
      respectively. Conversely, their concomitant overexpression markedly increased
      cell death even for a resistant type of breast cancer cells, MCF-7. Notably, we
      observed no cytotoxicity of our methodology on normal cells. In summary, this is
      the first demonstration that a dual approach using simultaneous overexpression of
      a cell penetrable form of Smac and TRAIL sensitize and promote apoptotic process
      even in resistant breast cancer cells.

PMID- 25586351
TI  - [Treat to target in ankylosing spondylitis].

PMID- 25586352
TI  - [Anti-inflammatory diet as influence and supplementary therapy of ankylosing
      spondylitis].

PMID- 25586350
TI  - Adiponectin inhibits VEGF-A in prostate cancer cells.
AB  - A role of adiponectin in tumorigenesis has recently been appreciated. Although
      plasma adiponectin levels in subjects with prostate cancer have been found to be
      significantly lower than in subjects with benign prostatic hyperplasia or in
      normal healthy controls, the underlying molecular mechanisms remain unknown.
      Here, we not only detected significant decreases in plasma adiponectin levels in
      prostate cancer patients, but also showed significant decreases in adiponectin
      receptor I (AdipoR1) levels in the resected prostate cancer specimen. Prostate
      cancer cell lines examined in the current study had all lower levels of
      adiponectin and AdipoR1, compared to normal healthy prostate tissue. Moreover,
      overexpression of adiponectin in prostate cancer cells decreased production of
      vascular endothelial growth factor A (VEGF-A), while adiponectin depletion
      increased VEGF-A. Furthermore, adiponectin seemed to activate AMPK/TSC2 to
      inhibit mTor-mediated activation of VEGF-A. Taken together, our data suggest that
      adiponectin may play an essential role in suppressing growth of prostate cancer
      cells through inhibition of VEGF-A-mediated cancer neovascularization.

PMID- 25586353
TI  - [The clinical characteristics of 26 cases of hypophosphatemia osteomalacia
      misdiagnosed as spondyloarthritis].
AB  - OBJECTIVE: To study and summarize the clinical features of hypophosphatemia
      osteomalacia (HO) misdiagnosed as spondyloarthritis (SpA), aiming to analyze the
      reasons of misdiagnosis and improve the prognosis of such patients. METHODS: A
      total of 26 cases of HO misdiagnosed as SpA were selected. Clinical features,
      laboratory tests, and image presentations were analyzed. Related literatures were
      reviewed. RESULTS: (1) Clinical characters: 26 patients were included (12 males
      and 14 females) with a median age of 38 years (range 20-60). The mean disease
      duration was 3.2 years (range 0.75 to 10 years). Of all the patients, 15 were
      diagnosed as tumor-induced HO, 4 were long-term oral adefovir dipivoxil-related
      HO, 3 were associated with Fanconi syndrome, 2 were related to
      hyperparathyroidism, while 2 were Sjogren's syndrome complicated with renal
      tubular acidosis. All of the 26 patients presented with low back pain including
      15 with night pain. The time of morning stiffness was about 30 minutes. Non
      steroidal anti-inflammatory drugs were given to each patient whereas with poor
      efficacy, neither did other agents work well, such as glucocorticoids, disease
      modifying anti-rheumatic drugs and biologics. (2) LABORATORY FINDINGS: the
      platelet count and inflammatory markers such as erythrocyte sedimentation rate, C
      reactive protein (CRP) were usually normal. The level of serum calcium was normal
      or slightly lower, nevertheless, all patients had hypophosphatemia and increased
      level of alkaline phosphatase (ALP). Patients with adefovir dipivoxil-related HO,
      Fanconi syndrome or Sjogren's syndrome complicated with renal tubular acidosis
      were characterized by hypokalemia, hyperchloremia and alkaline urine. Patients
      with hyperparathyroidism had elevated parathyroid hormone (PTH). Positive
      antinuclear antibodies (ANA) (titer >= 1: 320), anti-SSA/SSB antibodies were
      found in patients with Sjogren's syndrome. (3) Radiographic features: sacroiliac
      joint lesions were found in X-ray, CT, positron emission tomography (PET-CT) or
      MRI, however the lesions in sacrum or ilium were predominant rather than in
      joints. Abnormal bone imaging in ribs, long bones and soft tissues in addition to
      joints could be detected by bone scintigraphy. CONCLUSION: HO is not uncommon in
      daily practice. Besides SpA, other diseases should be considered in the setting
      of low-back pain and diseased sacroiliac joints. Comprehensive screening of bone
      metabolic parameters contributes to the timely diagnosis of HO.

PMID- 25586354
TI  - [Exploration of risk factors on the occurrence of osteoporotic vertebral fracture
      in patients with rheumatoid arthritis].
AB  - OBJECTIVE: To explore the prevalence of osteoporosis (OP) and vertebral
      osteoporotic fracture (OPF) and related risk factors in patients with rheumatoid
      arthritis (RA). METHOD: A total of 644 patients with RA from Jan. 2010 to Oct.
      2013 were recruited, anteroposterior and lateral X-rays examination of vertebral
      column (T5-L5) were conducted, and semi-quantity method were used as the standard
      for judging vertebral OPF. Meanwhile, patients' clinical and laboratory data
      including daily dosage of glucocorticoid, duration of glucocorticoid usage,
      cumulative amount dosage of glucocorticoid were recorded in details. 158 normal
      subjects were selected as control group. RESULTS: (1)The prevalence of vertebral
      OPF in patients with RA was 16.6%. Bone mineral density (BMD) of all measured
      lumbar vertebra in RA group were markedly decreased [(0.97 +/- 0.22) g/cm(2)].
      The total prevalence of OP at lumbar vertebra in RA was 17.9% (81/452), which was
      significantly higher than that of control group (4.4%, 7/158) (P < 0.001). (2)
      The percentage of OP in RA patients with vertebral OPF was significantly higher
      than that in patients without OPF [40.6% (41/101) vs 11.4% (40/351); P < 0.001].
      Patients with OPF were of older age, longer use of glucocorticoid, more
      cumulative amount dosage of glucocorticoid, longer disease duration, higher
      scores of health assessment questionnaires (HAQ) and increased ESR (P < 0.05).
      (3) Logistic regression analysis revealed that age (OR = 1.094, 95% CI 1.065
      1.125, P < 0.001) and gender (1 = male, 2 = female) (OR = 5.600, 95% CI 2.097
      15.087, P = 0.001) were the risk factors for the development of OP in RA, while
      body mass index (BMI) was the protective factor (OR = 0.770, 95% CI 0.696-0.853,
      P < 0.001). Age (OR = 1.031, 95% CI 1.009-1.053, P = 0.005) and occurrence of OP
      at lumbar vertebra (OR = 3.765, 95% CI 2.092-6.776, P < 0.001) were risk factors
      of the development of OPF in RA patients. Logistic regression analysis also
      showed that RA was the risk factor of OPF (OR = 4.716, 95% CI 1.987-11.192, P <
      0.001), even after the adjustment of age, gender and BMI. (4) Receiver operator
      characteristic(ROC) curve in RA patients with OPF has found that age-OPF and
      daily dosage of glucocorticoid-OPF AUCROC were 0.689 and 0.636 respectively. The
      cut-off value in ROC curve of age and daily dose or treatment course of
      glucocorticoid-OPF were 54.5 years and 6.25 mg (P < 0.001) , while duration of
      glucocorticoid usage-OPF AUCROC was 0.685, with cut-off value in ROC of age-OPF
      135 days (P < 0.001). CONCLUSION: Prevalence of OPF in patients with RA increases
      remarkably. Old age and OP at spine are risk factors related to the development
      of OPF in patients with RA.

PMID- 25586355
TI  - [Effects of active and passive smoking on chronic kidney disease in patients with
      type 2 diabetes mellitus].
AB  - OBJECTIVE: This study aimed to assess the effects of active and passive smoking
      on chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM).
      METHODS: Seven hundred and five patients with T2DM were recruited in the study
      and were divided into three groups based on smoking status as active smokers,
      passive smokers and non-smokers. Twenty-four hour urinary albumin excretion
      (24hUAE) was measured, and estimate glomerular filtration rate (eGFR) was
      calculated with age and blood creatinine levels. RESULTS: (1)The proportion of
      CKD in T2DM in the present study was 31.63% (223/705) with 28.6% (22/77) , 30.0%
      (15/50) and 29.6% (73/247) for non-smokers, passive smokers and active smokers in
      men, and 29.9% (40/134), 35.9% (66/184) and 7/13 for non-smokers, passive smokers
      and active smokers in women, respectively. In comparison with non-smokers, a
      higher risk of CKD was found in both passive and active smokers (OR = 1.07 and OR
      = 1.05 in men; OR = 1.31 and OR = 2.74 in women, respectively). (2) Compared with
      non-smokers, passive smokers had a significant higher risk for albuminuria in
      women (OR = 2.02, P = 0.016) . (3) After adjusting for gender, age, duration of
      T2DM, BMI, systolic blood pressure, glycosylated hemoglobin A1C and lipids, there
      was a significant decrease in eGFR between active and never smokers (P = 0.018)
      or passive smokers (P = 0.000) in women. No differences could be found in eGFR
      between each smoking statues in men. CONCLUSIONS: Smoking exposure alone confers
      a high risk for CKD in patients with T2DM. Our results highlight an importance in
      implementation of a smoke-free environment for patients with T2DM.

PMID- 25586356
TI  - [Bortezomib-based induction therapy followed by autologous hematopoietic stem
      cell transplantation in multiple myeloma].
AB  - OBJECTIVE: To evaluate the short-term and long-term effect of novel agents
      followed by autologous hematopoietic stem cell (ASCT) in Chinese multiple
      myeloma(MM) patients in order to find out the optimal therapeutic regimen for
      transplant-eligible patients. METHODS: Clinical data of 100 active MM patients
      receiving bortezomib-based induction regimens followed by high-dose melphalan and
      ASCT were retrospectively analyzed from June 1, 2006 to January 30, 2014.
      RESULTS: The overall response rates(ORR) after induction therapy, transplantation
      and consolidation and maintenance therapy were respectively 90.0%, 97.0%, and
      98.9%. The median progress free survival(PFS) was 42.3 months. The median overall
      survival(OS) was not reached. The cumulative near complete response
      (nCR)+complete respanse(CR) rate was no longer improved after 4 cycles of
      induction therapy for non-light chain type MM and two cycles for light-chain
      type. In newly-diagnosed light-chain type MM patients, the cumulative nCR+CR rate
      after 4 cycles of bortezomib plus dexamethasone (VD) regimen was similar to that
      of bortezomib, doxorubicin and dexamethasone (PAD). While for those non-light
      chain types, three drug-based regimen was better than two drug-based. PFS of
      patients receiving early ASCT was longer than that of late ASCT (50.7 months vs
      26.6 months, P = 0.023) . PFS in patients receiving autologous bone marrow stem
      cell transplantation (ABMSCT) was longer than that of autologous peripheral blood
      stem cell transplantation (APBSCT) (NA vs 36.1 months, P = 0.049) . Maintenance
      therapy was beneficial regardless of the response rate after ASCT. Patients with
      CR at any time during the therapy had longer PFS than those with nCR.
      CONCLUSIONS: Bortezomib-based therapy followed by ASCT is the first line therapy
      for transplant-eligible MM patients. Patients with different types of M protein
      require different induction regimens. Maintenance is beneficial to patients after
      ASCT, no matter whether a CR is reached or not. Patients with CR after induction
      or ASCT tend to have longer survival.

PMID- 25586357
TI  - [A report of seven cases of pulmonary sequestration complicated by aspergillosis
      and literature review].
AB  - OBJECTIVE: Pulmonary sequestration (PS) is a rare disease, and its clinical
      symptoms are usually related to subsequent pulmonary infections. We analyzed the
      clinical characteristics of PS complicated by aspergillosis, and reviewed related
      literature, so as to disclose the association between these two diseases.
      METHODS: Sixty-nine patients with surgery-confirmed PS in Peking Union Medical
      College Hospital between January 1990 and December 2013 were retrospectively
      analyzed, including seven cases complicated by aspergillosis. Clinical
      manifestation, imaging and surgery of these patients were analyzed. Literature
      focusing on PS complicated by aspergillosis in pubmed data base was reviewed.
      RESULTS: In these seven patients, four cases were male, and three cases were
      female. Age at diagnosis ranged from 29 to 58 years old. The interval from onset
      to definite diagnosis ranged from two weeks to 20 years. Clinical symptoms
      included productive cough in seven cases, hemoptysis in three cases, chest pain
      in two cases, and fever in one case. All cases were intralobar PS with four in
      the left lower lobe and three in the right lower lobe. Consolidation in chest CT
      was noted in six cases. Cavitation was positive in three cases. Surgery of lung
      lobe resection was performed in all patients. Aberrant arteries were found during
      operation with the origin from aortic artery in four cases, phrenic artery in two
      cases, and intercostal artery in one case. Aspergillosis was diagnosed by
      pathology in six cases and by lung tissue culture in one case. CONCLUSIONS: PS
      complicated by aspergillosis is extremely rare, but the trend of an increase in
      recent years has been noted. Strict and cautious examinations for microorganisms
      and pathology will help find relatively insidious aspergillosis.

PMID- 25586358
TI  - [The relationship between serum asymmetric dimethylarginine and ABCD2 score in
      transient ischemic attack patients].
AB  - OBJECTIVE: To investigate relationships between serum asymmetric dimethylarginine
      (ADMA) and transient ischemic attack (TIA). METHODS: Forty healthy controls and
      40 patients with TIA were enrolled in the present study. ABCD2 score was used to
      evaluate risk for future stroke. Serum ADMA levels were measured with ELISA
      analysis. RESULTS: Serum level of ADMA was higher in TIA group than that in
      control group [(0.52 +/- 0.06) mmol/L vs (0.23 +/- 0.04) mmol/L, P < 0.05]. In
      TIA subgroup, 19 cases (47.5%) developed cerebral infarction and 23 cases (57.5%)
      had no stroke history. There is positive correlation between serum ADMA levels
      and ABCD2 score in both cerebral infarction subjects (r = 0.560, P = 0.013), and
      no stroke history cases(r = 0.602, P = 0.002). TIA subjects were, then, divided
      in to two groups based on ABCD2 score as 0-3 group and >= 4 group. In general
      linear model analysis, ADMA level was associated with ABCD2 score (F = 4.39, P =
      0.043) after adjusted for age and gender. This situation hold true for subjects
      within cerebral infarction group (F = 7.327, P = 0.017) or non-previous stroke
      group(F = 12.300, P = 0.002) . No association could be found between ADMA level
      and ABCD2 score grouping in subjects with non-infarct (F = 0.523, P = 0.675) or
      stroke history (F = 0.274, P = 0.609). CONCLUSIONS: Elevated ADMA is associated
      with occurrence of TIA. Endothelial dysfunction may play an important role in the
      pathogenesis of TIA.

PMID- 25586359
TI  - [Inferior vena cava diameter and variability on longitudinal plane measured
      through ultrasonography from different sites: a comparison study].
AB  - OBJECTIVE: To investigate the inferior vena cava internal diameter (IVCID) and
      inferior vena cava variability (IVCV) on longitudinal plane measured from
      subcostal area and right mid-axillary line through ultrasonography and to find
      out if the measuring site and different respiratory status were related to the
      IVCID and IVCV. METHODS: A total of 127 patients were enrolled successively in
      Critical Care Medical Department of Peking Union Medical Hospital from November
      to December, 2013. IVCID and IVCV of patients on mechanical ventilation or with
      spontaneous breathing were measured longitudinally from subcostal area and right
      mid-axillary line. RESULTS: (1) Totally 124 out of the 127 patients achieved
      measurement from right mid-axillary line, while only 83 patients achieved
      measurement from subcostal area. The difference was statistically significant
      (chi(2) = 74.42, P < 0.01) . Eighty-one patients can be measured from both sites,
      with 44 had spontaneous breathing and 37 on mechanical ventilation. (2)Whether in
      spontaneous or mechanically ventilated patients, IVCID measured from subcostal
      area was statistically different from right mid-axillary line measurement at both
      end expiration and end inspiration. (3) In mechanically ventilated patients with
      IVCID >= 2 cm measured from subcostal area at end expiration, no statistical
      difference was found between the IVCID from right mid-axillary line and from
      subcostal area[ (2.25 +/- 0.32) cm vs (2.10 +/- 0.12) cm, P = 0.083]. In
      spontaneous breathing patients with IVCID >= 2 cm measured from subcostal area at
      end expiration, there were significant differences between the IVCID from right
      mid-axillary line and from subcostal area at both end expiration and end
      inspiration. The IVCV between the two sites were also statistically different. In
      mechanically ventilated patients with IVCID <= 1.5 cm measured from subcostal
      area at end expiration, there were significant difference between the IVCID from
      right mid-axillary line and from subcostal area [ (1.58 +/- 0.43) cm vs (1.09 +/-
      0.38) cm, P = 0.026]. In spontaneous breathing patients with IVCID <= 1.5 cm
      measured from subcostal area at end expiration, there were significant difference
      between the IVCID from right mid-axillary line and from subcostal area at both
      end expiration and end inspiration. The IVCV between the two sites were also
      statistically different. (4) Correlation analysis showed in mechanically
      ventilated patients, IVCID measured from right mid-axillary line at end
      expiration was correlated with the IVCID measured from subcostal area at end
      expiration(r = 0.565, P = 0.000). In spontaneous breathing patients, IVCID
      measured at end expiration from right mid-axillary line was correlated with the
      IVCID measured from subcostal area (r = 0.526, P = 0.000) . IVCID measured at end
      inspiration from right mid-axillary line was correlated with the IVCID measured
      from subcostal area (r = 0.454, P = 0.002). IVCV measured from right mid-axillary
      line was correlated with IVCV measured from subcostal area (r = 0.513, P =
      0.000). CONCLUSIONS: Inferior vena cava internal diameter and variability
      measured longitudinally through ultrasonography from subcostal area is different
      with measurements from right mid-axillary line. Measurements from the two sites
      are not replaceable with each other. Further studies are needed before the
      clinical use of inferior vena cava internal diameter and variability measured
      from right mid-axillary line.

PMID- 25586360
TI  - [Clinical analysis of gluten-related disease].
AB  - OBJECTIVE: To explore the diagnosis and treatment of gluten-related disorders
      (GRD). METHODS: Anti-gliadin antibodies(AGA), anti-tissue transglutaminase (tTG)
      antibody, deamidated gliadin peptides (DGP) antibody and serum specific IgG
      antibodies of 14 kinds of intolerable food were tested in people who developed
      chronic diarrhea after the intake of gluten diet. HLA-DQ2, HLA-DQ8 and intestinal
      endoscopic multiple biopsies would be performed further in patients with positive
      coeliac disease (CD)-specific serology. Gluten free diet was given to patients
      with positive CD-specific serology.One patient received prednisone (30 mg/d and
      diminished 5 mg/w). RESULTS: Nine patients were confirmed with celiac disease
      (CD) and four cases were suspected non-coeliac gluten sensitivity (NCGS) in 13
      patients with positive serologic tests. Twelve cases received effective therapy.
      In CD group, 6 cases were accompanied with comorbidities mainly autoimmune
      diseases and osteoporosis. The positive rates of AGA and tTG antibody were 9/9
      and 2/9 respectively in the CD group, while tTG antibody in the NCGS group were
      both negative.Endoscopic intestinal biopsy was performed in all 13 cases. Plasma
      cell proliferation and lymphocyte infiltration in the lamina propria without
      villus atrophy were identified in 4 cases, representing chronic inflammation of
      the small intestine. Villus atrophy was detected in 9 cases. Two patients with
      NCGS ingested gluten after 4 and 6 months of gluten-free diet respectively, and
      the number of bowel movements increased 1-2 times per day. CONCLUSIONS: The
      diagnosis of CD is mainly based on serologic tests and characteristic of
      histological features. CD may be companied by other autoimmune diseases or
      metabolic disease of bone. Lifelong adherence to a gluten free diet is the most
      basic and effective therapy.

PMID- 25586361
TI  - Activation of Wnt/beta-catenin/GSK3beta signaling during the development of
      diabetic cardiomyopathy.
AB  - BACKGROUND: As Wnt/beta-catenin/glycogen synthase kinase 3beta (GSK3beta)
      signaling has been implicated in myocardial injury and diabetic cardiomyopathy
      (DCM) is a major part of diabetic cardiovascular complications, we therefore
      investigated the alterations of Wnt/beta-catenin/GSK3beta signaling during the
      development of DCM. METHODS: The rat model of diabetes mellitus (DM) was
      established using a single intraperitoneal injection of streptozotocin (STZ, 60
      mg/kg). The alterations of Wnt/beta-catenin/GSK3beta signaling were determined 4,
      8, and 12 weeks following DM using Western blotting, immunohistochemistry, and
      quantitative real-time reverse transcriptase polymerase chain reaction. Cardiac
      pathology changes were evaluated using hematoxylin and eosin, Masson
      trichromatic, and terminal dUTP nick-end labeling staining. RESULTS: Histological
      analyses revealed that DM induced significant myocardial injury and progressive
      cardiomyocyte apoptosis. The protein and mRNA levels of Wnt2, beta-catenin, and c
      Myc were progressively increased 4, 8, and 12 weeks following DM. The expression
      of T-cell factor 4 and phosphorylated of GSK3beta on Ser9 were progressively
      increased. However, the expression of the endogenous Wnt inhibitor Dickkopf-1 was
      increased after STZ injection and then decreased as DCM developed. CONCLUSION:
      Wnt/beta-catenin/GSK3beta signaling pathway is activated in the development of
      DCM. Further investigation into the role of Wnt signaling during DCM will
      functionally find novel therapeutic target for DCM.

PMID- 25586364
TI  - Insights into the physical chemistry of materials from advances in HAADF-STEM.
AB  - The observation that, "New tools lead to new science"[P. S. Weiss, ACS Nano.,
      2012, 6(3), 1877-1879], is perhaps nowhere more evident than in scanning
      transmission electron microscopy (STEM). Advances in STEM have endowed this
      technique with several powerful and complimentary capabilities. For example, the
      application of high-angle annular dark-field imaging has made possible real-space
      imaging at sub-angstrom resolution with Z-contrast (Z = atomic number). Further
      advances have wrought: simultaneous real-space imaging and elemental
      identification by using electron energy loss spectroscopy (EELS); 3-dimensional
      (3D) mapping by depth sectioning; monitoring of surface diffusion by time
      sequencing of images; reduced electron energy imaging for probing graphenes; etc.
      In this paper we review how these advances, often coupled with first-principles
      theory, have led to interesting and important new insights into the physical
      chemistry of materials. We then review in detail a few specific applications that
      highlight some of these STEM capabilities. 

PMID- 25586363
TI  - Canine pancreatic-specific lipase concentrations in dogs with heart failure and
      chronic mitral valvular insufficiency.
AB  - BACKGROUND: Chronic mitral valvular insufficiency (CMVI) in dogs is very common
      and might cause clinical signs of congestion and poor tissue perfusion.
      HYPOTHESIS: Poor tissue perfusion from CMVI causes pancreatitis in dogs, as
      indicated by serum pancreatic lipase concentrations. ANIMALS: Sixty-two client
      owned dogs consisting of 40 dogs with different stages of heart failure from CMVI
      and 22 age-matched healthy dogs, based on full cardiac exam and routine
      laboratory tests. METHODS: Prospective, controlled, observational study. Serum
      canine pancreatic lipase immunoreactivity (cPLI) concentrations were determined
      by quantitative cPLI test in healthy and CMVI groups. RESULTS: Serum cPLI
      concentrations were 54.0 MUg/L (IQR: 38.0-78.8 MUg/L) in control, 55.0 MUg/L
      (IQR: 38.3-88.8 MUg/L) in ISACHC I, 115.0 MUg/L (IQR: 45.0-179.0 MUg/L) in ISACHC
      II and 223.0 MUg/L (IQR: 119.5-817.5 MUg/L) in ISACHC III. Close correlation to
      serum cPLI concentration was found in the left atrial to aorta (LA/Ao) ratio (r =
      0.597; P = .000) and the severity of heart failure (r = 0.530; P = .000).
      CONCLUSIONS AND CLINICAL IMPORTANCE: This study found CMVI is associated with
      pancreatic injury in congestive heart failure caused by CMVI. Therefore, periodic
      monitoring on cPLI could be useful in monitoring dogs in heart failure.

PMID- 25586362
TI  - Night-shift work and incident diabetes among African-American women.
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess shift work in relation to
      incident type 2 diabetes in African-American women. METHODS: In the Black Women's
      Health Study (BWHS), an ongoing prospective cohort study, we followed 28,041
      participants for incident diabetes during 2005-2013. They answered questions in
      2005 about having worked a night shift. We estimated HR and 95% CIs for incident
      diabetes using Cox proportional hazards models. The basic multivariable model
      included age, time period, family history of diabetes, education and
      neighbourhood socioeconomic status. In further models, we controlled for
      lifestyle factors and BMI. RESULTS: Over the 8 years of follow-up, there were
      1,786 incident diabetes cases. Relative to never having worked the night shift,
      HRs (95% CI) for diabetes were 1.17 (1.04, 1.31) for 1-2 years of night-shift
      work, 1.23 (1.06, 1.41) for 3-9 years and 1.42 (1.19, 1.70) for >= 10 years (p
      trend < 0.0001). The monotonic positive association between night-shift work and
      type 2 diabetes remained after multivariable adjustment (p-trend = 0.02). The
      association did not vary by obesity status, but was stronger in women aged <50
      years. CONCLUSIONS/INTERPRETATION: Long duration of shift work was associated
      with an increased risk of type 2 diabetes. The association was only partially
      explained by lifestyle factors and BMI. A better understanding of the mechanisms
      by which shift work may affect the risk of diabetes is needed in view of the high
      prevalence of shift work among workers in the USA.

PMID- 25586365
TI  - Microdialysis measurements of lamellar perfusion and energy metabolism during the
      development of laminitis in the oligofructose model.
AB  - REASONS FOR PERFORMING STUDY: Failure of lamellar energy metabolism, with or
      without ischaemia, may be important in the pathophysiology of sepsis-associated
      laminitis. OBJECTIVES: To examine lamellar perfusion and energy balance during
      laminitis development in the oligofructose model using tissue microdialysis.
      STUDY DESIGN: In vivo experiment. METHODS: Six Standardbred horses underwent
      laminitis induction using the oligofructose model (OFT group) and 6 horses were
      untreated controls (CON group). Microdialysis probes were placed in the lamellar
      tissue of one forelimb (all horses) as well as the skin dermis of the tail in OFT
      horses. Dialysate and plasma samples were collected every 2 h for 24 h and
      concentrations of energy metabolites (glucose, lactate, pyruvate) and standard
      indices of energy metabolism (lactate to glucose ratio [L:G] and lactate to
      pyruvate ratio [L:P]) determined. Microdialysis urea clearance was used to
      estimate changes in tissue perfusion. Data were analysed nonparametrically.
      RESULTS: Median glucose concentration decreased to <30% of baseline by 8 h in OFT
      lamellar (P = <0.01) and skin (P<0.01) dialysate. Lactate increased mildly in
      skin dialysate (P = 0.04) and plasma (P = 0.05) but not lamellar dialysate in OFT
      horses. Median pyruvate concentration decreased to <50% of baseline in OFT
      lamellar dialysate (P = 0.03). A >5-fold increase in median L:G compared with
      baseline occurred in OFT lamellar and skin dialysate (P<0.03). From a baseline of
      <20, median L:P increased to a peak of 80 in OFT skin and 38.7 in OFT lamellar
      dialysates (P<0.02); however, OFT lamellar dialysate L:P was not significantly
      different from CON. Urea concentration decreased significantly in OFT lamellar
      dialysate (increased urea clearance) but not in OFT skin or CON lamellar
      dialysate. CONCLUSIONS: Increased lamellar perfusion occurred during the
      development of sepsis-associated laminitis in the oligofructose model. Glucose
      concentrations in the lamellar interstitium decreased, suggesting increased
      glucose consumption but there was no definitive evidence of lamellar energy
      failure.

PMID- 25586366
TI  - Does interprofessional simulation increase self-efficacy: a comparative study.
AB  - OBJECTIVES: In this work, we have compared uniprofessional and interprofessional
      versions of a simulation education intervention, in an attempt to understand more
      about whether it improves trainees' self-efficacy. BACKGROUND:
      Interprofessionalism has been climbing the healthcare agenda for over 50 years.
      Simulation education attempts to create an environment for healthcare
      professionals to learn, without potential safety risks for patients. Integrating
      simulation and interprofessional education can provide benefits to individual
      learners. SETTING: The intervention took place in a high-fidelity simulation
      facility located on the campus of a large urban hospital. The centre provides
      educational activities for an Academic Health Sciences Centre. Approximately 2500
      staff are trained at the centre each year. PARTICIPANTS: One hundred and fifteen
      nurses and midwives along with 156 doctors, all within the early years of their
      postgraduate experience participated. All were included on the basis of their
      ongoing postgraduate education. METHODS: Each course was a one-day simulation
      course incorporating five clinical and one communication scenarios. After each a
      facilitated debriefing took place. A mixed methods approach utilised precourse
      and postcourse questionnaires measuring self-efficacy in managing emergency
      situations, communication, teamwork and leadership. RESULTS: Thematic analysis of
      qualitative data showed improvements in communication/teamwork and leadership,
      for doctors and nurses undergoing simulation training. These findings were
      confirmed by statistical analysis showing that confidence ratings improved in
      nurses and doctors overall (p<0.001). Improved outcomes from baseline were
      observed for interprofessional versus uniprofessional trained nurses (n=115;
      p<0.001). Postcourse ratings for doctors showed that interprofessional training
      was significantly associated with better final outcomes for a
      communication/teamwork dimension (n=156; p<0.05). CONCLUSIONS: This study
      provides evidence that simulation training enhances participants' self-efficacy
      in clinical situations. It also leads to increases in their perceived abilities
      relating to communication/teamwork and leadership/management of clinical
      scenarios. Interprofessional training showed increased positive effects on self
      efficacy for nurses and doctors.

PMID- 25586367
TI  - Association between duration of use of pharmacotherapy and smoking cessation:
      findings from a national survey.
AB  - OBJECTIVE: To investigate the association of the duration of use of prescription
      medications and nicotine replacement therapy (NRT) with smoking cessation using a
      national sample of the general population in the USA, controlling for nicotine
      dependence and sociodemographic variables. SETTING USA PARTICIPANTS: We used data
      from the 2010-2011 Tobacco Use Supplement to the US Current Population Survey. We
      limited the analysis to current daily smokers who made a quit attempt in the past
      year and former smokers who were a daily smoker 1 year prior to the survey
      (n=8263). Respondents were asked about duration of use of prescription medication
      (varenicline, bupropion, other) and NRT (nicotine patch, gum/lozenges, nasal
      spray and inhaler) for smoking cessation. PRIMARY OUTCOME MEASURE: Successful
      smoking cessation. Individuals who reported to have smoked at least 100
      cigarettes in their lifetime but were not smoking at all at the time of the
      interview and were a daily smoker 1 year prior to the interview were considered
      to have successfully quit smoking. RESULTS: After adjusting for daily cigarette
      consumption and sociodemographic covariates, we found evidence for an association
      between duration of pharmacotherapy use and smoking cessation (p<0.001). Adjusted
      cessation rates for those who used prescription medication or NRT for 5+ weeks
      were 28.8% and 27.8%, respectively. Adjusted cessation rates for those who used
      prescription medication or NRT for less than 5 weeks varied from 6.2% to 14.5%.
      Adjusted cessation rates for those who used only behavioural counselling and
      those who attempted to quit smoking unassisted were 16.1% and 16.4%,
      respectively. CONCLUSIONS: Use of pharmacotherapy for at least 5 weeks is
      associated with increased likelihood of successful smoking cessation. Results
      suggest that encouraging smokers who intend to quit to use pharmacotherapy and to
      adhere to treatment duration can help improve chances of successful cessation.

PMID- 25586368
TI  - Does the use of passive or active consent affect consent or completion rates, or
      dietary data quality? Repeat cross-sectional survey among school children aged 11
      12 years.
AB  - OBJECTIVES: An expectation of research is that participants should give fully
      informed consent. However, there is also a need to maximise recruitment to ensure
      representativeness. We explored the impact of passive or active parental consent
      on consent, completion rates and on dietary data quality in a survey among
      children aged 11-12 years. SETTING: Six middle schools in North-East England.
      PARTICIPANTS: All children aged 11-12 years attending the six middle schools were
      eligible to participate (n=1141). MAIN OUTCOMES:  PRIMARY OUTCOMES: whether or
      not each eligible child's parent gave consent and provided a complete dietary
      diary; whether or not a child completed their dietary diary but only among
      children who agreed to participate, and whether or not children providing diaries
      were classified as an under-reporter or not. RESULTS: Parents were more likely to
      consent passively than actively. This difference was greater among the more
      deprived: OR 16.9 (95% CI 5.7 to 50.2) in the least and 129.6 (95% CI 39.9 to
      420.6) in the most deprived quintile (test for interaction: method of consent by
      level of deprivation, p=0.02). For all children eligible, completion was more
      likely if passive consent was used (OR 2.8, 95% CI 2.2 to 3.7). When only
      children who gave consent are considered, completion was less likely when passive
      rather than active consent was used (OR 0.6, 95% CI 0.4 to 0.9). Completion rate
      decreased as level of deprivation increased; we found no evidence that the OR for
      the method of consent varied by level of deprivation. There was no evidence that
      the quality of dietary data, as measured by an assessment of under-reporting,
      differed by method of consent (OR 0.8, 95% CI 0.5 to 1.2). CONCLUSIONS: Passive
      consent led to a higher participation rate and a more representative sample
      without compromising data quality.

PMID- 25586369
TI  - Variation in local trust Do Not Attempt Cardiopulmonary Resuscitation (DNACPR)
      policies: a review of 48 English healthcare trusts.
AB  - OBJECTIVES: To explore Do Not Attempt Cardiopulmonary Resuscitation (DNACPR)
      policies from English acute, community and ambulance service Trusts for evidence
      of consistency and variation in implementation of national guidelines between
      healthcare organisations. SETTING: Acute, community or ambulance National Health
      Service (NHS) Trusts in England. PARTICIPANTS: 48 NHS Trusts. INTERVENTIONS:
      Freedom of information requests for adult DNACPR policies were sent to a random
      sample of Trusts. OUTCOMES: DNACPR policies were assessed on aspects identified
      from national guidelines including documentation, ethical and legal issues,
      decision-makers and involvement of others in DNACPR decisions as well as
      practical considerations such as validity, review and portability of decisions.
      RESULTS: Policies from 26 acute, 12 community and 10 ambulance service Trusts
      were reviewed. There was variation in terminology used (85% described documents
      as policies, 6% procedures and 8% guidelines). Only one quarter of Trusts used
      the recommended Resuscitation Council (UK) record form (or a modification of the
      form). There was variation in the terminology used which included DNAR, DNACPR,
      Not for CPR and AND (allow natural death). Accountability for DNACPR decisions
      rested with consultants at all acute Trusts and the most senior clinician at
      community Trusts. Most Trusts (74%) recommended discussion of decisions with a
      multidisciplinary team. Compliance with guidance requiring clinical staff to
      assess the patient for capacity and when to consult a lasting power of attorney
      or independent mental capacity advocate occurred less commonly. There was wide
      variation in the duration of time over which a DNACPR decision was considered
      valid as well as in the Trusts' approach to reviewing DNACPR decisions. The level
      of portability of DNACPR decisions between healthcare organisations was one of
      the greatest sources of variation. CONCLUSIONS: There is significant variation in
      the translation of the national DNACPR guidelines into English healthcare Trusts'
      DNACPR policies.

PMID- 25586370
TI  - Light cupula: the pathophysiological basis of persistent geotropic positional
      nystagmus.
AB  - OBJECTIVE: To clarify the pathophysiological basis of persistent geotropic
      positional nystagmus (PGN) in patients with the horizontal canal type of benign
      paroxysmal positional vertigo (H-BPPV), the time constant (TC) of nystagmus and
      the relationship between its slow phase eye velocity (SPV) and the angle of head
      rotation in supine were defined. METHODS: Geotropic or apogeotropic positional
      nystagmus was recorded by video-oculography and analysed three-dimensionally.
      RESULTS: Geotropic positional nystagmuses in patients with H-BPPV were classified
      as transient geotropic positional nystagmus with a TC of <=35 s or PGN with a TC
      of >35 s. Alternatively, the TC of persistent apogeotropic positional nystagmus
      (AN) in patients with H-BPPV was >35 s. The direction of the SPV of patients with
      PGN was opposite to that of patients with AN at each head position across the
      range of neutral head positions. The relationship between the SPV of patients
      with PGN and the angle of head rotation was linearly symmetrical against that of
      patients with AN with respect to a line drawn on the neutral head position.
      CONCLUSIONS: Since its TC was >35 s, it is suggested that PGN is induced by
      cupula deviation in response to gravity at each head position. It is also
      suggested that the direction of cupula deviation in patients with PGN is opposite
      to that of patients with AN across the neutral head positional range with no
      nystagmus where the long axis of cupula is in alignment with the axis of gravity.
      Since the pathophysiological basis of AN is considered a heavy cupula, it is
      suggested that PGN is conversely induced by a light cupula.

PMID- 25586371
TI  - Access to weight reduction interventions for overweight and obese patients in UK
      primary care: population-based cohort study.
AB  - OBJECTIVES: To investigate access to weight management interventions for
      overweight and obese patients in primary care. SETTING: UK primary care
      electronic health records. PARTICIPANTS: A cohort of 91 413 overweight and obese
      patients aged 30-100 years was sampled from the Clinical Practice Research
      Datalink (CPRD). Patients with body mass index (BMI) values >=25 kg/m(2) recorded
      between 2005 and 2012 were included. BMI values were categorised using WHO
      criteria. INTERVENTIONS: Interventions for body weight management, including
      advice, referrals and prescription of antiobesity drugs, were evaluated. PRIMARY
      AND SECONDARY OUTCOME MEASURES: The rate of body weight management interventions
      and time to intervention were the main outcomes. RESULTS: Data were analysed for
      91 413 patients, mean age 56 years, including 55 094 (60%) overweight and 36 319
      (40%) obese, including 4099 (5%) with morbid obesity. During the study period,
      90% of overweight patients had no weight management intervention recorded.
      Intervention was more frequent among obese patients, but 59% of patients with
      morbid obesity had no intervention recorded. Rates of intervention increased with
      BMI category. In morbid obesity, rates of intervention per 1000 patient years
      were: advice, 60.2 (95% CI 51.8 to 70.4); referral, 75.7 (95% CI 69.5 to 82.6)
      and antiobesity drugs 89.9 (95% CI 85.0 to 95.2). Weight management interventions
      were more often accessed by women, older patients, those with comorbidity and
      those in deprivation. Follow-up of body weight subsequent to interventions was
      infrequent. CONCLUSIONS: Limited evidence of weight management interventions in
      primary care electronic health records may result from poor recording of advice
      given, but may indicate a lack of patient access to appropriate body weight
      management interventions in primary care.

PMID- 25586372
TI  - Does prewarming the i-gel supraglottic airway device fit the larynx better
      compared to keeping it at room temperature for non-paralysed, sedated patients: a
      randomised controlled trial.
AB  - OBJECTIVE: This study aimed to test the hypothesis that the i-gel supraglottic
      airway device would fit the larynx and provide better sealing pressure if
      prewarmed to 42 degrees C relative to the device kept at room temperature in non
      paralysed, sedated patients. METHODS: A total of 74 adult patients were assigned
      to the warm (i-gel prewarmed to 42 degrees C; W group; 37 patients) or the
      control (i-gel kept at room temperature; C group; 37 patients) groups.
      Anaesthesia was induced with propofol and fentanyl. The i-gel was prewarmed to 42
      degrees C for 30 min before insertion in the W group, but kept at room
      temperature (approximately 23 degrees C) for the C group. The number of attempts
      made until successful insertion and sealing pressure were compared between the
      two groups. RESULTS: Insertion was successful with one attempt in 35 cases each
      for the W and C groups. Two attempts were needed in two cases for the W group and
      one case for the C group. There was one failed attempt in the C group, but none
      in the W group. None of the differences between the two groups were significant
      (p=0.51). Sealing pressure was slightly, but not significantly, higher in the W
      group than in the C group (W group 22.6+/-6.1 cm H2O; C group 20.7+/-6.1 cm H2O;
      p=0.15). CONCLUSIONS: Prewarming of the i-gel to 42 degrees C did not increase
      the success rate of insertion, nor did it significantly increase sealing pressure
      in anaesthetised, non-paralysed patients. Our data suggest that we can keep the i
      gel at room temperature for emergency airway management for non-paralysed,
      sedated patients. TRIAL REGISTRATION NUMBER: University Medical Information
      Network, Japan 000012287.

PMID- 25586373
TI  - Identifying postoperative atrial fibrillation in cardiac surgical patients
      posthospital discharge, using iPhone ECG: a study protocol.
AB  - INTRODUCTION: Postoperative atrial fibrillation (AF) occurs in 30-40% of patients
      after cardiac surgery. Identification of recurrent postoperative AF is required
      to initiate evidence-based management to reduce the risk of subsequent stroke.
      However, as AF is often asymptomatic, recurrences may not be detected after
      discharge. This study determines feasibility and impact of a self-surveillance
      programme to identify recurrence of postoperative AF in the month of posthospital
      discharge. METHODS AND ANALYSIS: This is a feasibility study, using a cross
      sectional study design, of self-screening for AF using a hand-held single-lead
      iPhone electrocardiograph device (iECG). Participants will be recruited from the
      cardiothoracic surgery wards of the Royal North Shore Hospital and North Shore
      Private Hospital, Sydney, Australia. Cardiac surgery patients admitted in sinus
      rhythm and experiencing a transient episode of postoperative AF will be eligible
      for recruitment. Participants will be taught to take daily ECG recordings for 1
      month posthospital discharge using the iECG and will be provided education
      regarding AF, including symptoms and health risks. The primary outcome is the
      feasibility of patient self-monitoring for AF recurrence using an iECG. Secondary
      outcomes include proportion of patients identified with recurrent AF; estimation
      of stroke risk and patient knowledge. Process outcomes and qualitative data
      related to acceptability of patient's use of the iECG and sustainability of the
      screening programme beyond the trial setting will also be collected. ETHICS AND
      DISSEMINATION: Primary ethics approval was received on 25 February 2014 from
      Northern Sydney Local Health District Human Resource Ethics Committee, and on 17
      July 2014 from North Shore Private Hospital Ethics Committee. Results will be
      disseminated via forums including, but not limited to, peer-reviewed publications
      and presentation at national and international conferences. TRIAL REGISTRATION
      NUMBER: ACTRN12614000383662.

PMID- 25586374
TI  - Directly grown nanostructured electrodes for high volumetric energy density
      binder-free hybrid supercapacitors: a case study of CNTs//Li4Ti5O12.
AB  - Hybrid supercapacitor (HSC), which typically consists of a Li-ion battery
      electrode and an electric double-layer supercapacitor electrode, has been
      extensively investigated for large-scale applications such as hybrid electric
      vehicles, etc. Its application potential for thin-film downsized energy storage
      systems that always prefer high volumetric energy/power densities, however, has
      not yet been explored. Herein, as a case study, we develop an entirely binder
      free HSC by using multiwalled carbon nanotube (MWCNT) network film as the cathode
      and Li(4)Ti(5)O(12) (LTO) nanowire array as the anode and study the volumetric
      energy storage capability. Both the electrode materials are grown directly on
      carbon cloth current collector, ensuring robust mechanical/electrical contacts
      and flexibility. Our 3 V HSC device exhibits maximum volumetric energy density of
      ~4.38 mWh cm(-3), much superior to those of previous supercapacitors based on
      thin-film electrodes fabricated directly on carbon cloth and even comparable to
      the commercial thin-film lithium battery. It also has volumetric power densities
      comparable to that of the commercial 5.5 V/100 mF supercapacitor (can be operated
      within 3 s) and has excellent cycling stability (~92% retention after 3000
      cycles). The concept of utilizing binder-free electrodes to construct HSC for
      thin-film energy storage may be readily extended to other HSC electrode systems.

PMID- 25586375
TI  - Medical image retrieval and analysis by Markov random fields and multi-scale
      fractal dimension.
AB  - Many Content-based Image Retrieval (CBIR) systems and image analysis tools employ
      color, shape and texture (in a combined fashion or not) as attributes, or
      signatures, to retrieve images from databases or to perform image analysis in
      general. Among these attributes, texture has turned out to be the most relevant,
      as it allows the identification of a larger number of images of a different
      nature. This paper introduces a novel signature which can be used for image
      analysis and retrieval. It combines texture with complexity extracted from
      objects within the images. The approach consists of a texture segmentation step,
      modeled as a Markov Random Field process, followed by the estimation of the
      complexity of each computed region. The complexity is given by a Multi-scale
      Fractal Dimension. Experiments have been conducted using an MRI database in both
      pattern recognition and image retrieval contexts. The results show the accuracy
      of the proposed method in comparison with other traditional texture descriptors
      and also indicate how the performance changes as the level of complexity is
      altered. 

PMID- 25586376
TI  - Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic
      cancer cell plasticity.
AB  - In adaptation to oncogenic signals, pancreatic ductal adenocarcinoma (PDAC) cells
      undergo epithelial-mesenchymal transition (EMT), a process combining tumor cell
      dedifferentiation with acquisition of stemness features. However, the mechanisms
      linking oncogene-induced signaling pathways with EMT and stemness remain largely
      elusive. Here, we uncover the inflammation-induced transcription factor NFATc1 as
      a central regulator of pancreatic cancer cell plasticity. In particular, we show
      that NFATc1 drives EMT reprogramming and maintains pancreatic cancer cells in a
      stem cell-like state through Sox2-dependent transcription of EMT and stemness
      factors. Intriguingly, NFATc1-Sox2 complex-mediated PDAC dedifferentiation and
      progression is opposed by antithetical p53-miR200c signaling, and inactivation of
      the tumor suppressor pathway is essential for tumor dedifferentiation and
      dissemination both in genetically engineered mouse models (GEMM) and human PDAC.
      Based on these findings, we propose the existence of a hierarchical signaling
      network regulating PDAC cell plasticity and suggest that the molecular decision
      between epithelial cell preservation and conversion into a dedifferentiated
      cancer stem cell-like phenotype depends on opposing levels of p53 and NFATc1
      signaling activities. 

PMID- 25586379
TI  - Vasoactive intestinal peptide is a local mediator in a gut-brain neural axis
      activating intestinal gluconeogenesis.
AB  - Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation
      of a gut-brain neural axis. However, the local mediator activating gluconeogenic
      genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal
      peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6
      phosphatase gene in vivo, (ii) the activation of IGN by propionate is
      counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the
      submucosal plexus are increased under the action of propionate. These data
      support the role of VIP as a local neuromodulator released by intrinsic enteric
      neurons and responsible for the induction of IGN through a VPAC1 receptor
      dependent mechanism in enterocytes. 

PMID- 25586377
TI  - Unsaturated fatty acids induce non-canonical autophagy.
AB  - To obtain mechanistic insights into the cross talk between lipolysis and
      autophagy, two key metabolic responses to starvation, we screened the autophagy
      inducing potential of a panel of fatty acids in human cancer cells. Both
      saturated and unsaturated fatty acids such as palmitate and oleate, respectively,
      triggered autophagy, but the underlying molecular mechanisms differed. Oleate,
      but not palmitate, stimulated an autophagic response that required an intact
      Golgi apparatus. Conversely, autophagy triggered by palmitate, but not oleate,
      required AMPK, PKR and JNK1 and involved the activation of the BECN1/PIK3C3 lipid
      kinase complex. Accordingly, the downregulation of BECN1 and PIK3C3 abolished
      palmitate-induced, but not oleate-induced, autophagy in human cancer cells.
      Moreover, Becn1(+/-) mice as well as yeast cells and nematodes lacking the
      ortholog of human BECN1 mounted an autophagic response to oleate, but not
      palmitate. Thus, unsaturated fatty acids induce a non-canonical, phylogenetically
      conserved, autophagic response that in mammalian cells relies on the Golgi
      apparatus. 

PMID- 25586378
TI  - TFG clusters COPII-coated transport carriers and promotes early secretory pathway
      organization.
AB  - In mammalian cells, cargo-laden secretory vesicles leave the endoplasmic
      reticulum (ER) en route to ER-Golgi intermediate compartments (ERGIC) in a manner
      dependent on the COPII coat complex. We report here that COPII-coated transport
      carriers traverse a submicron, TFG (Trk-fused gene)-enriched zone at the ER/ERGIC
      interface. The architecture of TFG complexes as determined by three-dimensional
      electron microscopy reveals the formation of flexible, octameric cup-like
      structures, which are able to self-associate to generate larger polymers in
      vitro. In cells, loss of TFG function dramatically slows protein export from the
      ER and results in the accumulation of COPII-coated carriers throughout the
      cytoplasm. Additionally, the tight association between ER and ERGIC membranes is
      lost in the absence of TFG. We propose that TFG functions at the ER/ERGIC
      interface to locally concentrate COPII-coated transport carriers and link exit
      sites on the ER to ERGIC membranes. Our findings provide a new mechanism by which
      COPII-coated carriers are retained near their site of formation to facilitate
      rapid fusion with neighboring ERGIC membranes upon uncoating, thereby promoting
      interorganellar cargo transport. 

PMID- 25586380
TI  - Herpesvirus in the oral cavity of children with leukaemia and its impact on the
      oral bacterial community profile.
AB  - AIMS: This cross-sectional study investigated the association between eight
      herpesviruses and the bacterial community profiles from the oral cavity of
      children with and without leukaemia. METHODS: Sixty participants (aged 3-13),
      divided into the leukaemia group (LG) and healthy group (HG), were evaluated.
      Collection of medical data, intraoral examination and collection of clinical
      specimens were carried out. Single PCR and nested-PCR techniques were used to
      identify the viral types; denaturing gradient gel electrophoresis (DGGE) and real
      time PCR techniques were used to evaluate the profile and abundance of bacterial
      communities. RESULTS: All the children with leukaemia were positive for at least
      one type of herpesvirus, compared with healthy participants (33.3%; p<0.000).
      Human cytomegalovirus (HCMV; 46.7%), human herpesvirus-7 (HHV-7; 20%) and HHV-8
      (77.3%) were in higher prevalence in the LG (p <= 0.01). Children with leukaemia
      had positive associations with the presence of HCMV, HHV-7 and HHV-8 in the oral
      cavity when under chemotherapy (p<0.05). There was a qualitative (means of DGGE
      bands) and quantitative (means of 16S rRNA gene abundance) difference in relation
      to the bacterial community between the two groups (p<0.05). CONCLUSIONS: Based on
      the results, the prevalence of herpesviruses and the qualitative bacterial
      profiles was higher in children with leukaemia and HCMV, HHV-7 and HHV-8 were
      related to the use of chemotherapy. Moreover, HHV-6 was correlated with an
      increased bacterial community profile in patients with leukaemia (p<0.05). More
      attention should be paid to the oral health of these individuals, mainly those
      under chemotherapy, in order to prevent infections by opportunistic pathogens.

PMID- 25586382
TI  - Deposition of ultra thin CuInS2 absorber layers by ALD for thin film solar cells
      at low temperature (down to 150  degrees C).
AB  - Two new processes for the atomic layer deposition of copper indium sulfide
      (CuInS2) based on the use of two different sets of precursors are reported. Metal
      chloride precursors (CuCl, InCl3) in combination with H2S imply relatively high
      deposition temperature (Tdep = 380  degrees C), and due to exchange reactions,
      CuInS2 stoechiometry was only achieved by depositing In2S3 layers on a CuxS film.
      However, the use of acac- metal precursors (Cu(acac)2, In(acac)3) allows the
      direct deposition of CuInS2 at temperature as low as 150  degrees C, involving in
      situ copper-reduction, exchange reaction and diffusion processes. The morphology,
      crystallographic structure, chemical composition and optical band gap of thin
      films were investigated using scanning electronic microscope, x-ray diffraction
      under grazing incidence conditions, x-ray fluorescence, energy dispersive
      spectrometry, secondary ion mass spectrometry, x-ray photoelectron spectroscopy
      and UV-vis spectroscopy. Films were implemented as ultra-thin absorbers in a
      typical CIS-solar cell architecture and allowed conversion efficiencies up to
      2.8%.

PMID- 25586381
TI  - Mutation detection in formalin-fixed prostate cancer biopsies taken at the time
      of diagnosis using next-generation DNA sequencing.
AB  - AIMS: Assessing whether next-generation DNA sequencing (NGS) can be used to
      screen prostate cancer for multiple gene alterations in men routinely diagnosed
      with this disease and/or who are entered into clinical trials. Previous studies
      are limited and have reported only low success rates. METHODS: We marked areas of
      cancer on H&E-stained sections from formalin-fixed needle biopsies, and used
      these as templates to dissect cancer-rich tissue from adjacent unstained
      sections. DNA was prepared using a Qiagen protocol modified to maximise DNA
      yield. The DNA was screened simultaneously for mutations in 365 cancer-related
      genes using an Illumina HiSeq 2000 NGS platform. RESULTS: From 63 prostate
      cancers examined, 59(94%) of the samples yielded at least 30 ng of DNA, the
      minimum amount of DNA considered suitable for NGS analysis. Patients in the
      D'Amico high-risk group yielded an average of 1033 ng, intermediate-risk patients
      401 ng, and low-risk patients 97 ng. NGS of eight samples selected from high-risk
      and intermediate-risk groups gave a median exon read depth of 962 and detected
      TMPRRS2-ERG fusions, as well as a variety of mutations including those in the
      SPOP, TP53, ATM, MEN1, NBPF10, NCOR2, PIK3CB and MAP2K5 (MEK5) genes.
      CONCLUSIONS: Using the methods presented here, NGS technologies can be used to
      screen a high proportion of patients with prostate cancer for mutations in cancer
      related genes in tissue samples opening up its general use in the context of
      clinical trials or routine diagnosis.

PMID- 25586383
TI  - Brain ischemia, endoplasmic reticulum stress, and astroglial activation: new
      insights.

PMID- 25586385
TI  - Developing a specialist obesity infrastructure: an example from current
      strategies in England.

PMID- 25586386
TI  - Research priorities in 2012 for the effective management of childhood obesity.
AB  - In 2010, the Management Stream of the Australasian Child and Adolescent Obesity
      Research Network (ACAORN) undertook a Delphi survey asking 'What research
      questions remain to be addressed in the effective management of child and
      adolescent obesity?' Members of ACAORN, the Child and Adolescent Obesity Clinics
      of Australasia Network (CAOCOA-Net) and attendees at the Child Obesity symposium
      at the annual scientific meeting for the Australian and New Zealand Obesity
      Society (ANZOS) contributed to three rounds of survey development. Although
      reasonable concordance in ratings was evident for all 10 questions, 'determining
      the best strategies for long-term weight management' and 'how best to support the
      primary healthcare system to achieve these strategies' were clearly identified as
      the highest research priorities. Other priorities included 'how best to identify
      the right children with whom to intervene' and 'managing factors which impact on
      service delivery'. Identifying priority research areas from those working in the
      field offers the opportunity to stimulate research collaboration and provide
      justification for funding applications. 

PMID- 25586384
TI  - Soil-borne microbiome: linking diversity to function.
AB  - Soil microorganisms are sensitive to environment disturbances, and such
      alterations have consequences on microbial diversity and functions. Our
      hypothesis is that alpha diversity of microbial communities and functional
      diversity decrease from undisturbed to disturbed soils, with consequences for
      functional redundancy in the soil ecosystem. To test this hypothesis, we used
      soil DNA shotgun metagenomics approach to assess the soil microbiome in a
      chronosequence of land-use from a native tropical forest, followed by
      deforestation and cultivation of soybean croplands and pasture in different
      seasons. Agriculture and pasture soils were among the most diverse and presented
      higher functional redundancy, which is important to maintain the ecosystem
      functioning after the forest conversion. On the other hand, the ecosystem
      equilibrium in forest is maintained based on a lower alpha diversity but higher
      abundance of microorganisms. Our results indicate that land-use change alters the
      structure and composition of microbial communities; however, ecosystem
      functionality is overcome by different strategies based on the abundance and
      diversity of the communities. 

PMID- 25586387
TI  - Morbidly obese paediatric patients are not adequately screened for comorbidities.
AB  - Although childhood obesity is common, many paediatric practitioners are not
      familiar with screening for its associated, serious comorbidities. We aimed to
      determine the adequacy of screening for nine well-recognized comorbidities in
      outpatients with severe morbid obesity (body mass index [BMI] >=50 kg m(-2) )
      seen in a large tertiary paediatric hospital. Patients with a BMI of >=50 kg m(
      2) seen at Texas Children's Hospital during calendar year 2009 were identified.
      Their medical records were reviewed for any documentation where hypertension,
      cardiac dysfunction, sleep apnoea, hepatosteatosis, diabetes, pseudotumour
      cerebri, dyslipidemia, orthopaedic issues and depression were noted and/or
      addressed as evidence of clinician awareness of these problems. We identified 123
      patients seen at least once in 2009, with an average of 3.4 physician visits per
      patient and by an average of 2 different specialists. Hypertension screening was
      the most documented (91% of patients) and depression screening was the least
      documented (41%) in this patient cohort. Twelve patients (10%) had documented
      screening for all nine comorbidities. Overall, 55 patients (45%) had five or
      fewer of the nine comorbidities noted and/or addressed in the medical record.
      Adequate screening for comorbidities occurs in approximately half of children
      with severe morbid obesity, which means that many of these comorbidities are not
      being identified or treated. Educational programmes and new methodologies are
      needed to ensure comprehensive care of children with morbid obesity. 

PMID- 25586388
TI  - Difference in weight loss based on ethnicity, age and comorbidity status in a
      publicly funded adult weight management centre: 1-year results.
AB  - Limited evidence is available on the effectiveness of publicly funded weight loss
      (WL) clinics. We examined the 1-year WL outcomes and investigated predictors of
      WL and discontinuation of 1566 overweight and obese adults, who attended the
      Wharton Medical Clinic (WMC) weight management centre for at least 6 months.
      Overall, 42.7% (n = 669) of the entire sample achieved a >=5%WL over the entire
      follow-up period from July 2008 to February 2012. On average, patients lost 5.6
      +/- 7.2 kg (5.0 +/- 6.3%) of initial body weight (BW), while a subsample of
      patients attending the clinic for at least 1 year had a mean weight reduction of
      6.6 +/- 7.9 kg (5.9 +/- 7.2%) of BW. Older patients were more likely to achieve a
      greater WL in comparison with young patients while White patients and those
      without type 2 diabetes (T2D) lost almost twice as much weight and %BW in
      comparison with Asian patients and patients with T2D, respectively (P < 0.05).
      Discontinuing patients did not differ in terms of sex, body mass index, education
      and smoking status from those who continued treatment (P > 0.05). Results of this
      study demonstrate that the WMC provides a practical model for clinically
      effective lifestyle-based treatment, accessible to a wide range of
      demographically diverse adults. 

PMID- 25586389
TI  - Bariatric surgery attrition secondary to psychological barriers.
AB  - Despite the effectiveness of bariatric surgery only 49% of the patients that
      enroll in bariatric surgery programmes complete the surgery. This study attempts
      to identify psychological barriers to bariatric surgery. A sample of 471 patients
      who were screened for medical indications for surgery, adequate health insurance
      and medical/psychological contraindications, were used. Participants were
      predominantly female (71.8%) and Caucasian (68.4%) with a mean body mass index
      (+/-standard deviation [SD]) of 47.84 (+/-7.53) and mean age (+/-SD) of 40.59 (+/
      10.79). A total of 69.2% completed surgery (63.2% gastric bypass, 35.6% gastric
      band, 1.2% gastric sleeve). Participants with lower levels of global surgical
      anxiety, a preference for the gastric bypass, a childhood or adolescent onset of
      obesity, and more experience dieting, were more likely to complete surgery. No
      significant differences were found among groups for specific surgical anxieties
      or medical comorbidities. These findings suggest that factors that patients
      routinely report as surgical motivators, including comorbidities, may be
      necessary, but are not sufficient, for surgical completion. Other factors, such
      as a global surgical anxiety, and the patient's belief in their ability to lose
      weight without surgery, may play a large role in surgical attrition. 

PMID- 25586390
TI  - The effectiveness of secondary and tertiary care lifestyle intervention in
      morbidly obese patients: a 1-year non-randomized controlled pragmatic clinical
      trial.
AB  - In this non-randomized clinical pragmatic trial, we aimed to compare the
      effectiveness of an outpatient intensive lifestyle intervention (ILI) programme
      conducted in a tertiary care obesity rehabilitation centre with an outpatient
      moderate lifestyle intervention (MLI) programme at a secondary care obesity
      centre. Effectiveness was measured in terms of the 1-year effect each programme
      had on body weight, physical activity and health-related quality of life (HRQL).
      A total of 232 morbidly obese subjects were recruited to the ILI group and 140 to
      the MLI group, with retention rates of 78% and 44%, respectively. The ILI group
      had a significantly larger mean (95% confidence interval [CI]) weight loss than
      the MLI group, 11% (9%, 12%) vs. 2% (1%, 6%), P < 0.001, and a larger proportion
      of completers attaining >=5% weight loss (71% vs. 33%), P < 0.001. Compared with
      the MLI group, the ILI group achieved a significant larger mean (95% CI) increase
      in the physical dimension of HRQL 6.9 (4.4, 9.3), P < 0.001, the mental dimension
      of HRQL 4.4 (1.4, 7.4), P = 0.018 and in the emotional dimension of HRQL 17.8
      (12.8, 22.6), P < 0.001. There were no significant differences in terms of
      changes in physical activity. Compared with MLI, ILI was associated with
      significantly larger weight loss and better HRQL. 

PMID- 25586391
TI  - A model case of a positive outcome in super-super obesity.
AB  - For an increasing number of obese patients, bariatric surgery is considered as
      the treatment of choice after the failure of conventional strategies. While
      numerous studies on bariatric surgery have shown substantial health benefits,
      there is a broad inter-individual variation in the long-term outcome, which is
      insufficiently understood. Here we show a favourable long-term outcome following
      multidisciplinary care in a super-super-obese patient. The patient suffered from
      numerous typically obesity-associated comorbidities and limitations. He underwent
      multidisciplinary care including two-step bariatric intervention. Endoscopic
      intragastric balloon positioning was followed by gastric sleeve surgery without
      Roux-en-Y gastric bypass. His body weight dropped from 260 kg (body mass index
      [BMI] 79.4 kg m(-2) ) to 85 kg (BMI 25.9 kg m(-2) ) within 16 months and
      continued to be stable at 90 kg (BMI 27.8 kg m(-2) ) at the end of the follow-up
      period of 48 months. The loss of excess body weight was associated with the
      remission of numerous obesity-related comorbidities and with a concomitant
      pronounced increase in the quality of life and in the socioeconomic status.
      Eventually, the patient was able to lead a normal life with a decreased risk of
      long-term complications. We attribute the positive long-term outcome to the
      following potential determinants: individualized bariatric surgery,
      multidisciplinary care, the patient's long-term compliance, adequate adherence to
      the aftercare, physical exercise after surgery, family support, the cooperation
      of the primary care physician and the financial coverage by the health insurance.
      Some of these factors remain to be evaluated as predictors of a favourable long
      term outcome in prospective trials. 

PMID- 25586392
TI  - Mesenteric vein thrombosis after laparoscopic sleeve gastrectomy.
AB  - Mesenteric vein thrombosis is a rare complication of bariatric laparoscopic
      surgery. We report a case of a 47-year-old man with obesity who had mesenteric
      vein thrombosis 14 days after laparoscopic sleeve gastrectomy. He was treated
      with heparin anticoagulation with a good therapeutic response. This case and
      literature review illustrate that mesenteric vein thrombosis has to be included
      in the differential diagnosis of abdominal pain after a bariatric procedure and
      listed formally as a complication of bariatric surgery. 

PMID- 25586393
TI  - Associations between executive functioning, coping, and psychosocial functioning
      after acquired brain injury.
AB  - OBJECTIVES: To examine the relationships between executive functioning, coping,
      depressive symptoms, and quality of life in individuals with neuropsychiatric
      symptoms after acquired brain injury (ABI). DESIGN: Cross-sectional study.
      METHODS: Individuals (n = 93) in the post-acute and chronic phase (>3 months)
      after ABI and their significant others (N = 58) were recruited from outpatient
      clinics of four mental health centres in the Netherlands. Outcome measures were
      the Trail Making Test, Stroop Colour Word Test, Frontal Systems Behavioural
      Scale, Utrecht Coping List, Patient Health Questionnaire, and Life Satisfaction
      Questionnaire. Data were analysed with multiple regression analyses. RESULTS:
      Self-reported executive dysfunction was associated with greater use of passive
      coping styles (beta = .37, p < .01), and passive coping, in turn, was associated
      with lower quality of life (beta = -.57, p < .001) and more depressive symptoms
      (beta = .65, p < .001). Problem-focused coping was associated with higher quality
      of life among individuals who reported better executive functioning (beta = -.94,
      p < .05). Performances on executive functioning tests were not associated with
      coping, depressive symptoms, or quality of life. CONCLUSIONS: For clinicians,
      these data indicate that individuals who report greater difficulties with
      executive functioning after ABI are inclined to use maladaptive passive coping
      styles, which should be targeted in treatment. In comparison, individuals who
      report greater difficulties with executive functioning should not be prompted to
      use problem-focused coping styles. These individuals may benefit from other
      coping styles, such as the use of seeking social support or acceptance of
      problems. PRACTITIONER POINTS: Coping influences the association between
      executive functioning and quality of life. Individuals who report difficulties
      with executive functioning after ABI may be inclined to use passive coping
      styles, which are maladaptive. Problem-focused coping strategies may be more
      useful for individuals who have strong executive abilities. This study was a
      cross-sectional study; thus, a cause-and-effect relationship could not be
      established between executive functioning, coping, and psychosocial functioning.
      As this research was part of standard clinical care, non-traditional tests for
      executive functioning were not administered.

PMID- 25586394
TI  - Scopolamine provocation-based pharmacological MRI model for testing procognitive
      agents.
AB  - There is a huge unmet need to understand and treat pathological cognitive
      impairment. The development of disease modifying cognitive enhancers is hindered
      by the lack of correct pathomechanism and suitable animal models. Most animal
      models to study cognition and pathology do not fulfil either the predictive
      validity, face validity or construct validity criteria, and also outcome measures
      greatly differ from those of human trials. Fortunately, some pharmacological
      agents such as scopolamine evoke similar effects on cognition and cerebral
      circulation in rodents and humans and functional MRI enables us to compare
      cognitive agents directly in different species. In this paper we report the
      validation of a scopolamine based rodent pharmacological MRI provocation model.
      The effects of deemed procognitive agents (donepezil, vinpocetine, piracetam,
      alpha 7 selective cholinergic compounds EVP-6124, PNU-120596) were compared on
      the blood-oxygen-level dependent responses and also linked to rodent cognitive
      models. These drugs revealed significant effect on scopolamine induced blood
      oxygen-level dependent change except for piracetam. In the water labyrinth test
      only PNU-120596 did not show a significant effect. This provocational model is
      suitable for testing procognitive compounds. These functional MR imaging
      experiments can be paralleled with human studies, which may help reduce the
      number of false cognitive clinical trials. 

PMID- 25586396
TI  - Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study.
AB  - Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have
      clinically relevant effects in alcohol and drug addiction. Although recent
      studies have investigated the effects of psilocybin in various populations, there
      have been no studies on the efficacy of psilocybin for alcohol dependence. We
      conducted a single-group proof-of-concept study to quantify acute effects of
      psilocybin in alcohol-dependent participants and to provide preliminary outcome
      and safety data. Ten volunteers with DSM-IV alcohol dependence received orally
      administered psilocybin in one or two supervised sessions in addition to
      Motivational Enhancement Therapy and therapy sessions devoted to preparation for
      and debriefing from the psilocybin sessions. Participants' responses to
      psilocybin were qualitatively similar to those described in other populations.
      Abstinence did not increase significantly in the first 4 weeks of treatment (when
      participants had not yet received psilocybin), but increased significantly
      following psilocybin administration (p < 0.05). Gains were largely maintained at
      follow-up to 36 weeks. The intensity of effects in the first psilocybin session
      (at week 4) strongly predicted change in drinking during weeks 5-8 (r = 0.76 to r
      = 0.89) and also predicted decreases in craving and increases in abstinence self
      efficacy during week 5. There were no significant treatment-related adverse
      events. These preliminary findings provide a strong rationale for controlled
      trials with larger samples to investigate efficacy and mechanisms. TRIAL
      REGISTRATION: NCT02061293.

PMID- 25586395
TI  - Standardization of formulations for the acute amino acid depletion and loading
      tests.
AB  - The acute tryptophan depletion and loading and the acute tyrosine plus
      phenylalanine depletion tests are powerful tools for studying the roles of
      cerebral monoamines in behaviour and symptoms related to various disorders. The
      tests use either amino acid mixtures or proteins. Current amino acid mixtures
      lack specificity in humans, but not in rodents, because of the faster disposal of
      branched-chain amino acids (BCAAs) by the latter. The high content of BCAA (30
      60%) is responsible for the poor specificity in humans and we recommend, in a 50g
      dose, a control formulation with a lowered BCAA content (18%) as a common control
      for the above tests. With protein-based formulations, alpha-lactalbumin is
      specific for acute tryptophan loading, whereas gelatine is only partially
      effective for acute tryptophan depletion. We recommend the use of the whey
      protein fraction glycomacropeptide as an alternative protein. Its BCAA content is
      ideal for specificity and the absence of tryptophan, tyrosine and phenylalanine
      render it suitable as a template for seven formulations (separate and combined
      depletion or loading and a truly balanced control). We invite the research
      community to participate in standardization of the depletion and loading
      methodologies by using our recommended amino acid formulation and developing
      those based on glycomacropeptide. 

PMID- 25586397
TI  - The thalamic reticular nucleus: a functional hub for thalamocortical network
      dysfunction in schizophrenia and a target for drug discovery.
AB  - The thalamus (comprising many distinct nuclei) plays a key role in facilitating
      sensory discrimination and cognitive processes through connections with the
      cortex. Impaired thalamocortical processing has long been considered to be
      involved in schizophrenia. In this review we focus on the thalamic reticular
      nucleus (TRN) providing evidence for it being an important communication hub
      between the thalamus and cortex and how it may play a key role in the
      pathophysiology of schizophrenia. We first highlight the functional neuroanatomy,
      neurotransmitter localisation and physiology of the TRN. We then present evidence
      of the physiological roles of the TRN in relation to oscillatory activity,
      cognition and behaviour. Next we discuss the role of the TRN in rodent models of
      risk factors for schizophrenia (genetic and pharmacological) and provide evidence
      for TRN deficits in schizophrenia. Finally we discuss new drug targets for
      schizophrenia in relation to restoring TRN circuitry dysfunction. 

PMID- 25586398
TI  - The adverse health effects of synthetic cannabinoids with emphasis on psychosis
      like effects.
AB  - Cannabis use is associated with an increased risk of psychosis in vulnerable
      individuals. Cannabis containing high levels of the partial cannabinoid receptor
      subtype 1 (CB1) agonist tetrahydrocannabinol (THC) is associated with the
      induction of psychosis in susceptible subjects and with the development of
      schizophrenia, whereas the use of cannabis variants with relatively high levels
      of cannabidiol (CBD) is associated with fewer psychotic experiences. Synthetic
      cannabinoid receptor agonists (SCRAs) are full agonists and often more potent
      than THC. Moreover, in contrast to natural cannabis, SCRAs preparations contain
      no CBD so that these drugs may have a higher psychosis-inducing potential than
      cannabis. This paper reviews the general toxicity profile and the adverse effects
      of SCRAs with special emphasis on their psychosis-inducing risk. The review shows
      that, compared with the use of natural cannabis, the use of SCRAs may cause more
      frequent and more severe unwanted negative effects, especially in younger,
      inexperienced users. Psychosis and psychosis-like conditions seem to occur
      relatively often following the use of SCRAs, presumably due to their high potency
      and the absence of CBD in the preparations. Studies on the relative risk of SCRAs
      compared with natural cannabis to induce or evoke psychosis are urgently needed. 

PMID- 25586399
TI  - Repeated administration of aripiprazole produces a sensitization effect in the
      suppression of avoidance responding and phencyclidine-induced hyperlocomotion and
      increases D2 receptor-mediated behavioral function.
AB  - The present study investigated how repeated administration of aripiprazole (a
      novel antipsychotic drug) alters its behavioral effects in two behavioral tests
      of antipsychotic activity and whether this alteration is correlated with an
      increase in dopamine D2 receptor function. Male adult Sprague-Dawley rats were
      first repeatedly tested with aripiprazole (3, 10 and 30 mg/kg, subcutaneously
      (sc)) or vehicle in a conditioned avoidance response (CAR) test or a
      phencyclidine (PCP) (3.20 mg/kg, sc)-induced hyperlocomotion test daily for five
      consecutive days. After 2-3 days of drug-free retraining or resting, all rats
      were then challenged with aripiprazole (1.5 or 3.0 mg/kg, sc). Repeated
      administration of aripiprazole progressively increased its inhibition of
      avoidance responding and PCP-induced hyperlocomotion. More importantly, rats
      previously treated with aripiprazole showed significantly lower avoidance
      response and lower PCP-induced hyperlocomotion than those previously treated with
      vehicle in the challenge tests. An increased sensitivity to quinpirole (a
      selective D2/3 agonist) in prior aripiprazole-treated rats was also found in the
      quinpirole-induced hyperlocomotion test, suggesting an enhanced D2/3-mediated
      function. These findings suggest that aripiprazole, despite its distinct receptor
      mechanisms of action, induces a sensitization effect similar to those induced by
      other antipsychotic drugs and this effect may be partially mediated by brain
      plasticity involving D2/3 receptor systems. 

PMID- 25586401
TI  - Schizophrenia drug discovery and development in an evolving era: are new drug
      targets fulfilling expectations?
AB  - Current therapeutics for schizophrenia, the typical and atypical antipsychotic
      class of drugs, derive their therapeutic benefit predominantly by antagonism of
      the dopamine D2 receptor subtype and have robust clinical benefit on positive
      symptoms of the disease with limited to no impact on negative symptoms and
      cognitive impairment. Driven by these therapeutic limitations of current
      treatments and the recognition that transmitter systems beyond the dopaminergic
      system in particular glutamatergic transmission contribute to the etiology of
      schizophrenia significant recent efforts have focused on the discovery and
      development of novel treatments for schizophrenia with mechanisms of action that
      are distinct from current drugs. Specifically, compounds selectively targeting
      the metabotropic glutamate receptor 2/3 subtype, phosphodiesterase subtype 10,
      glycine transporter subtype 1 and the alpha7 nicotinic acetylcholine receptor
      have been the subject of intense drug discovery and development efforts. Here we
      review recent clinical experience with the most advanced drug candidates
      targeting each of these novel mechanisms and discuss whether these new agents are
      living up to expectations. 

PMID- 25586402
TI  - Classic psychedelic use is associated with reduced psychological distress and
      suicidality in the United States adult population.
AB  - Mental health problems are endemic across the globe, and suicide, a strong
      corollary of poor mental health, is a leading cause of death. Classic psychedelic
      use may occasion lasting improvements in mental health, but the effects of
      classic psychedelic use on suicidality are unknown. We evaluated the
      relationships of classic psychedelic use with psychological distress and
      suicidality among over 190,000 USA adult respondents pooled from the last five
      available years of the National Survey on Drug Use and Health (2008-2012) while
      controlling for a range of covariates. Lifetime classic psychedelic use was
      associated with a significantly reduced odds of past month psychological distress
      (weighted odds ratio (OR)=0.81 (0.72-0.91)), past year suicidal thinking
      (weighted OR=0.86 (0.78-0.94)), past year suicidal planning (weighted OR=0.71
      (0.54-0.94)), and past year suicide attempt (weighted OR=0.64 (0.46-0.89)),
      whereas lifetime illicit use of other drugs was largely associated with an
      increased likelihood of these outcomes. These findings indicate that classic
      psychedelics may hold promise in the prevention of suicide, supporting the view
      that classic psychedelics' most highly restricted legal status should be
      reconsidered to facilitate scientific study, and suggesting that more extensive
      clinical research with classic psychedelics is warranted. 

PMID- 25586403
TI  - Subchronic administration of short-acting naltrexone has no effect on striatal
      dopamine transporter availability, food intake or body weight gain in rats.
AB  - The opioid receptor antagonist naltrexone is successfully used in the treatment
      of opioid and alcohol dependence. However, questions have been raised about
      possible anhedonic side effects, because the opioid system is directly involved
      in hedonic responses to natural rewarding activities, possibly due to its
      indirect effects on the striatal dopamine transporter (DAT). In order to test
      this hypothesis, 30 rats were randomized to either a 10-day treatment with 3
      mg/kg short-acting naltrexone or vehicle. No significant differences between the
      groups were found in striatal DAT availability, cumulative food intake (for 48 or
      72 h), body weight gain and abdominal fatpad weight. Thus, the results of this
      study suggest that (sub)chronic treatment with short-acting naltrexone does not
      induce possible anhedonic effects. However, it cannot be ruled out the anhedonic
      effect of naltrexone is only short-lived and thus not detected in the current
      study. Therefore, future studies are needed to study possible acute anhedonic
      effects at several time points shortly after short-acting naltrexone
      administration and to directly compare the possible anhedonic effects of long
      acting with those of short-acting opioid antagonists. 

PMID- 25586404
TI  - Vintage treatments for PTSD: a reconsideration of tricyclic drugs.
AB  - Serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors (SSRI)
      are the first-line recommended drug treatments for post-traumatic stress disorder
      (PTSD); but despite their benefits, much residual pathology remains and no new
      drugs have yet emerged with a clearly demonstrated benefit for treating the
      disorder. A case is made that tricyclic drugs deserve a closer look, based on
      their ability to affect several of the main neurotransmitters that are relevant
      to PTSD. Their promising efficacy, which was shown 30 years ago, had not been
      followed up, until a recent trial of desipramine found advantages over a SSRI in
      PTSD with comorbid alcohol dependence. Opportunities exist for studying newer and
      purportedly safer tricyclic formulations, as well as further the work with older,
      established compounds. A reappraisal of their risk:benefit ratio seems in order,
      when treating PTSD. 

PMID- 25586405
TI  - Microscopic nephrocalcinosis in chronic kidney disease patients.
AB  - BACKGROUND: Experimental data indicate that microscopic calcium phosphate
      deposition in the kidney (nephrocalcinosis) may accelerate progression of chronic
      kidney disease (CKD). Data on the prevalence, risk factors and implications of
      nephrocalcinosis in CKD patients are scarce. A mineral metabolism disorder could
      play an important pathogenetic role, as suggested by recent protocol biopsy
      findings in incident renal transplant recipients. METHODS: Kidney biopsy
      cylinders of CKD patients, collected between January 1989 and December 2007, were
      screened for the presence of nephrocalcinosis. Only patients with >=1 parathyroid
      hormone (PTH) level available within 180 days of the biopsy were eligible for
      inclusion (n = 211). Demographics and mineral metabolism parameters were
      retrieved from medical files. Data on renal death (up to December 2012) were
      obtained from the Flemish ESRD registry. Baseline biopsies from 110 deceased
      kidney transplant donors served as controls. RESULTS: The prevalence of
      nephrocalcinosis in kidney donors and patients with CKD 1-2, CKD 3-4 and CKD 5-5D
      was 4.6, 14.3, 20.2 and 54.0%, respectively (P < 0.0001). Among CKD patients,
      patients with nephrocalcinosis were characterized by lower estimated GFR, lower
      serum bicarbonate level and higher serum PTH and calcium level. In multivariate
      regression analysis, high serum PTH, calcium and creatinine level, and low serum
      bicarbonate level were all significantly and independently associated with
      nephrocalcinosis. Serum phosphorus level, but not nephrocalcinosis predicted
      renal death, independent of renal function. CONCLUSIONS: Our data demonstrate
      that prevalence rates of nephrocalcinosis increase with increasing CKD stage to
      reach more than 50% in end-stage renal disease patients and suggest that acid
      base and mineral metabolism disturbances are implicated in its pathogenesis.

PMID- 25586406
TI  - Socio-economic status influences chronic kidney disease prevalence in primary
      care: a community-based cross-sectional analysis.
AB  - BACKGROUND: Primary care chronic kidney disease (CKD) registers report widely
      varying prevalence within the UK. We examined the effects of laboratory
      ascertainment and adjusting for practice-level variables on the variation in CKD
      prevalence. We carried out an Ayrshire-wide laboratory database analysis of
      primary care practices (PCPs). METHODS: We analysed 54 PCPs with 313 639
      registered patients aged >= 18. All patients with a low estimated glomerular
      filtration rate (<60 mL/min/1.73 m(2)) had their serum creatinine values
      extracted from 1st January 2009 to 31st March 2012. Individuals with CKD stage 3
      5 were identified with an algorithm that confirmed chronicity. These data were
      linked to PCP attributes from Information Services Division, Scotland. Using
      laboratory-ascertained CKD prevalence, we examined whether adjusting for practice
      level factors [socio-economic status (SES), rurality and patients to general
      practitioner ratio (PGR)] and patient-level factors (age, gender) explained some
      of the observed variation among PCPs. Individual and combined hierarchical
      multilinear regression models were used. RESULTS: Eighteen thousand two hundred
      and eighty-five (5.8%) had CKD stage 3-5 on 31 March 2011. SES, rurality and PGR
      predicted 39% (F(3,50) = 12.37, P < 0.001) of the variation in prevalence with
      SES exerting the most influence (25%). With the stepwise addition of explanatory
      variables, variation between practices fell from 3.9-fold using PCP register
      prevalence to laboratory ascertained (3.1-fold variation), with age and gender
      adjustment (further fall to 2.1-fold), and lastly to 1.8-fold variation with
      adjustment for SES. Funnel plots using these adjustments reduced the number of
      outliers outside of 3 SD from 15 to 7 to 6, and outliers between 2 and 3 SD by 16
      to 13 to 5. CONCLUSIONS: Laboratory ascertainment is practicable, reduces
      variation and facilitates benchmarking. PCP attributes other than age and gender
      impact on prevalence. Over a third of variation in CKD prevalence among PCPs can
      be explained by rurality, PGR and especially SES even after age and gender
      stratification.

PMID- 25586407
TI  - Hydrogenations at room temperature and atmospheric pressure with mesoionic
      carbene-stabilized borenium catalysts.
AB  - 1,2,3-Triazolylidene-based mesoionic carbene boranes have been synthesized in a
      convenient one-pot protocol from the corresponding 1,2,3-triazolium salts, base,
      and borane. Borenium ions are obtained by hydride abstraction and serve as
      catalysts in mild hydrogenation reactions of imines and unsaturated N
      heterocycles at ambient pressure and temperature. 

PMID- 25586400
TI  - Glutamate and dopamine in schizophrenia: an update for the 21st century.
AB  - The glutamate and dopamine hypotheses are leading theories of the pathoaetiology
      of schizophrenia. Both were initially based on indirect evidence from
      pharmacological studies supported by post-mortem findings, but have since been
      substantially advanced by new lines of evidence from in vivo imaging studies.
      This review provides an update on the latest findings on dopamine and glutamate
      abnormalities in schizophrenia, focusing on in vivo neuroimaging studies in
      patients and clinical high-risk groups, and considers their implications for
      understanding the biology and treatment of schizophrenia. These findings have
      refined both the dopamine and glutamate hypotheses, enabling greater anatomical
      and functional specificity, and have been complemented by preclinical evidence
      showing how the risk factors for schizophrenia impact on the dopamine and
      glutamate systems. The implications of this new evidence for understanding the
      development and treatment of schizophrenia are considered, and the gaps in
      current knowledge highlighted. Finally, the evidence for an integrated model of
      the interactions between the glutamate and dopamine systems is reviewed, and
      future directions discussed. 

PMID- 25586408
TI  - Controlled release of a sparingly water-soluble anticancer drug through pH
      responsive functionalized gold-nanoparticle-decorated liposomes.
AB  - The binding and detachment of carboxyl-modified gold nanoparticles from liposomes
      is used for controlled drug delivery. This study reveals that the binding and
      detachment of nanoparticles from liposomes depends on the degree of hydration of
      the liposomes. Liposomes with a lower hydration level undergo stronger
      electrostatic interactions with negatively charged gold nanoparticles, thus
      leading to a slower detachment of the carboxyl-modified gold nanoparticles under
      gastric conditions. Therefore, under gastric conditions, gold-nanoparticle
      decorated dipalmitoylphosphatidylcholine (DPPC) liposomes exhibit an at least ten
      times-slower drug release compared to gold-nanoparticle-decorated 1,2-dimyristoyl
      sn-glycero-3-phosphocholine (DMPC) liposomes, although both liposomes in the bare
      state fail to pursue controlled release. Our study also reveals that one can
      modulate the drug-release rate by simply varying the concentration of
      nanoparticles. This study highlights a novel strategy for the controlled release
      of drug molecules from liposomes. 

PMID- 25586411
TI  - Induction suspension plasma sprayed biological-like hydroxyapatite coatings.
AB  - Substituted hydroxyapatite coatings with different ions (Mg, Na, K, Cl, F) have
      been developed by the induction suspension plasma spray process. Suspensions were
      prepared with sol-gel. The main objective of this study was to demonstrate that
      induction suspension plasma spray technology possesses high material composition
      flexibility that allows as-sprayed coatings to closely mimic natural bone
      composition. Long-term in vitro behaviour of as-sprayed substituted coatings was
      evaluated with simulated body fluid. Data on the suspensions showed the formation
      of a pure hydroxyapatite phase. Transmission electron microscopy characterized
      various preparation stages of the suspensions. As-sprayed samples were
      distinguished by X-ray diffraction and scanning electron microscopy. Substituted
      elements were quantified by neutron activation. A well-crystallized
      hydroxyapatite phase was produced with concentration in various substitutions
      very close to natural bone composition. Ca/P and (Ca + Mg + Na + K)/P ratios
      provided evidence of the introduction of different cations into apatite
      structures. The immersion of samples into simulated body fluid led to the
      nucleation and growth of a flake-like octacalcium phosphate crystal layer at the
      surface of as-sprayed coatings after one week. Proof of octacalcium phosphate
      transformation and its partial dissolution and direct re-precipitation into
      apatite was disclosed by local energy dispersive spectroscopy and microstructure
      observation. Formation of a Ca/P ratio gradient from the precipitated layer
      surface to the as-sprayed coatings interface was observed after four weeks once
      the octacalcium phosphate crystals reached a critical size, resulting in the
      formation of a rich apatite layer at the interface after six weeks. A set of
      mechanisms has been proposed to explain these findings. 

PMID- 25586410
TI  - Multitrait indices to predict worm length and number in sheep with natural, mixed
      predominantly Teladorsagia circumcincta infection.
AB  - Accurately identifying resistance to gastrointestinal nematode infections
      requires the ability to identify animals with low and high intensities of
      infection. The pathogenic effects of nematodes depend upon both the length and
      number of worms, neither of which can be measured in live animals. Indices that
      predict these quantities are urgently needed. Monthly fecal egg counts,
      bodyweights, IgA concentrations and pepsinogen concentrations were measured on
      Scottish Blackface sheep naturally infected with a mixture of nematodes,
      predominantly Teladorsagia circumcincta. Worm number and average worm length were
      available on over 500 necropsied lambs. We derived predictive indices for worm
      length and number using linear combinations of traits measured in live animals.
      The correlations between the prediction values and the observed values were 0.55
      for worm length and 0.51 for worm number. These indices can be used to identify
      the most resistance and susceptible lambs.

PMID- 25586409
TI  - Maternal heavy alcohol use and toddler behavior problems: a fixed effects
      regression analysis.
AB  - Using data from the longitudinal Norwegian Mother and Child Cohort Study, the
      aims of the current study were to examine associations between postnatal maternal
      heavy alcohol use and toddler behavior problems, taking both observed and
      unobserved confounding factors into account by employing fixed effects regression
      models. Postnatal maternal heavy alcohol use (defined as drinking alcohol 4 or
      more times a week, or drinking 7 units or more per alcohol use episode) and
      toddler internalizing and externalizing behavior problems were assessed when the
      toddlers were aged 18 and 36 months. Maternal psychopathology, civil status and
      negative life events last year were included as time-variant covariates. Maternal
      heavy alcohol use was associated with toddler internalizing and externalizing
      behavior problems (p < 0.001) in the population when examined with generalized
      estimating equation models. The associations disappeared when observed and
      unobserved sources of confounding were taken into account in the fixed effects
      models [(p = 0.909 for externalizing behaviors (b = 0.002, SE = 0.021), p = 0.928
      for internalizing behaviors (b = 0.002, SE = 0.023)], with an even further
      reduction of the estimates with the inclusion of time-variant confounders. No
      causal effect was found between postnatal maternal heavy alcohol use and toddler
      behavior problems. Increased levels of behavior problems among toddlers of heavy
      drinking mothers should therefore be attributed to other adverse characteristics
      associated with these mothers, toddlers and families. This should be taken into
      account when interventions aimed at at-risk families identified by maternal heavy
      alcohol use are planned and conducted. 

PMID- 25586412
TI  - A low-cost, high-performance system for fluorescence lateral flow assays.
AB  - We demonstrate a fluorescence lateral flow system that has excellent sensitivity
      and wide dynamic range. The illumination system utilizes an LED, plastic lenses
      and plastic and colored glass filters for the excitation and emission light.
      Images are collected on an iPhone 4. Several fluorescent dyes with long Stokes
      shifts were evaluated for their signal and nonspecific binding in lateral flow. A
      wide range of values for the ratio of signal to nonspecific binding was found,
      from 50 for R-phycoerythrin (R-PE) to 0.15 for Brilliant Violet 605. The long
      Stokes shift of R-PE allowed the use of inexpensive plastic filters rather than
      costly interference filters to block the LED light. Fluorescence detection with R
      PE and absorbance detection with colloidal gold were directly compared in lateral
      flow using biotinylated bovine serum albumen (BSA) as the analyte. Fluorescence
      provided linear data over a range of 0.4-4,000 ng/mL with a 1,000-fold signal
      change while colloidal gold provided non-linear data over a range of 16-4,000
      ng/mL with a 10-fold signal change. A comparison using human chorionic
      gonadotropin (hCG) as the analyte showed a similar advantage in the fluorescent
      system. We believe our inexpensive yet high-performance platform will be useful
      for providing quantitative and sensitive detection in a point-of-care setting. 

PMID- 25586413
TI  - Sensitive detection of capsaicinoids using a surface plasmon resonance sensor
      with anti-homovanillic Acid polyclonal antibodies.
AB  - Recently, highly functional biosensors have been developed in preparation for
      possible large-scale terrorist attacks using chemical warfare agents. Practically
      applicable sensors are required to have various abilities, such as high
      portability and operability, the capability of performing rapid and continuous
      measurement, as well as high sensitivity and selectivity. We developed the
      detection method of capsaicinoids, the main component of some lachrymators, using
      a surface plasmon resonance (SPR) immunosensor as an on-site detection sensor.
      Homovanillic acid, which has a vanillyl group similar to capsaicinoids such as
      capsaicin and dihydrocapsaicin, was bound to Concholepas concholepas hemocyanin
      (CCH) for use as an immunogen to generate polyclonal antibodies. An indirect
      competitive assay was carried out to detect capsaicinoids using SPR sensor chips
      on which different capsaicin analogues were immobilized. For the sensor chip on
      which 4-hydroxy-3-methoxybenzylamine hydrochloride was immobilized, a detection
      limit of 150 ppb was achieved. We found that the incubation time was not required
      and the detection can be completed in five minutes. 

PMID- 25586414
TI  - Opening Study on the Development of a New Biosensor for Metal Toxicity Based on
      Pseudomonas fluorescens Pyoverdine.
AB  - To date, different kinds of biosensing elements have been used effectively for
      environmental monitoring. Microbial cells seem to be well-suited for this task:
      they are cheap, adaptable to variable field conditions and give a measurable
      response to a broad number of chemicals. Among different pollutants, heavy metals
      are still a major problem for the environment. A reasonable starting point for
      the selection of a biorecognition element to develop a biosensor for metals could
      be that of a microorganism that exhibits good mechanisms to cope with metals.
      Pseudomonads are characterized by the secretion of siderophores (e.g.,
      pyoverdine), low-molecular weight compounds that chelate Fe3+ during iron
      starvation. Pyoverdine is easily detected by colorimetric assay, and it is
      suitable for simple online measurements. In this work, in order to evaluate
      pyoverdine as a biorecognition element for metal detection, the influence of
      metal ions (Fe3+, Cu2+, Zn2+), but also of temperature, pH and nutrients, on
      microbial growth and pyoverdine regulation has been studied in P. fluorescens.
      Each of these variables has been shown to influence the synthesis of siderophore:
      for instance, the lower the temperature, the higher the production of pyoverdine.
      Moreover, the concentration of pyoverdine produced in the presence of metals has
      been compared with the maximum allowable concentrations indicated in
      international regulations (e.g., 98/83/EC), and a correlation that could be
      useful to build a colorimetric biosensor has been observed. 

PMID- 25586416
TI  - Development of a Fluorescence Resonance Energy Transfer (FRET)-Based DNA
      Biosensor for Detection of Synthetic Oligonucleotide of Ganoderma boninense.
AB  - An optical DNA biosensor based on fluorescence resonance energy transfer (FRET)
      utilizing synthesized quantum dot (QD) has been developed for the detection of
      specific-sequence of DNA for Ganoderma boninense, an oil palm pathogen. Modified
      QD that contained carboxylic groups was conjugated with a single-stranded DNA
      probe (ssDNA) via amide-linkage. Hybridization of the target DNA with conjugated
      QD-ssDNA and reporter probe labeled with Cy5 allows for the detection of related
      synthetic DNA sequence of Ganoderma boninense gene based on FRET signals.
      Detection of FRET emission before and after hybridization was confirmed through
      the capability of the system to produce FRET at 680 nm for hybridized sandwich
      with complementary target DNA. No FRET emission was observed for non
      complementary system. Hybridization time, temperature and effect of different
      concentration of target DNA were studied in order to optimize the developed
      system. The developed biosensor has shown high sensitivity with detection limit
      of 3.55 * 10-9 M. TEM results show that the particle size of QD varies in the
      range between 5 to 8 nm after ligand modification and conjugation with ssDNA.
      This approach is capable of providing a simple, rapid and sensitive method for
      detection of related synthetic DNA sequence of Ganoderma boninense. 

PMID- 25586415
TI  - Recent advances in fluorescent arylboronic acids for glucose sensing.
AB  - Continuous glucose monitoring (CGM) is crucial in order to avoid complications
      caused by change in blood glucose for patients suffering from diabetes mellitus.
      The long-term consequences of high blood glucose levels include damage to the
      heart, eyes, kidneys, nerves and other organs, among others, caused by malign
      glycation of vital protein structures. Fluorescent monitors based on arylboronic
      acids are promising candidates for optical CGM, since arylboronic acids are
      capable of forming arylboronate esters with 1,2-cis-diols or 1,3-diols fast and
      reversibly, even in aqueous solution. These properties enable arylboronic acid
      dyes to provide immediate information of glucose concentrations. Thus, the
      replacement of the commonly applied semi-invasive and non-invasive techniques
      relying on glucose binding proteins, such as concanavalin A, or enzymes, such as
      glucose oxidase, glucose dehydrogenase and hexokinases/glucokinases, might be
      possible. The recent progress in the development of fluorescent arylboronic acid
      dyes will be emphasized in this review. 

PMID- 25586417
TI  - Transcription factor glioma-associated oncogene homolog 1 is required for
      transforming growth factor-beta1-induced epithelial-mesenchymal transition of non
      small cell lung cancer cells.
AB  - Epithelial-mesenchymal transition (EMT) is the process by which epithelial cells
      depolarize and acquire a mesenchymal phenotype, and is a common early step in the
      process of metastasis. Patients with lung cancer frequently already have distant
      metastases when they are diagnosed, highlighting the requirement for early and
      effective interventions to control metastatic disease. Transforming growth factor
      beta1 (TGF-beta1) is able to induce EMT, however the molecular mechanism of this
      remains unclear. In the current study, TGF-beta1 was reported to induce EMT and
      promote the migration of non-small cell lung cancer (NSCLC) cells. A notable
      observation was that EMT induction was accompanied by the upregulation of human
      glioma-associated oncogene homolog 1 (Gli1) mRNA and protein levels. Furthermore,
      Gli1 levels were depleted by small interfering RNA, and the Gli1 inhibitor GANT
      61 attenuated the TGF-beta1-mediated induction of EMT and cell migration. The
      results of the current study suggest that Gli1 regulates TGF-beta1-induced EMT,
      which may provide a novel therapeutic target to inhibit metastasis in patients
      with NSCLC.

PMID- 25586418
TI  - Importance of scrotum pulling during diagnostic laparoscopy for impalpable
      testis.
AB  - OBJECTIVES: To evaluate the significance of a scrotum pulling maneuver during
      diagnostic laparoscopy for impalpable testis in order to determine whether an
      initial scrotal or inguinal incision should be carried out. METHODS: A total of
      75 patients undergoing diagnostic laparoscopy were included in the present study.
      If the vas deferens and spermatic vessels were noted to enter the internal
      inguinal ring, the affected scrotum was pulled downwards and the movements of the
      cord structures were observed. If inferior movement of the cord structures at the
      internal inguinal ring were noted, a scrotal approach was preferred. In the
      absence of cord structure movement, an inguinal approach was carried out first.
      RESULTS: In 59 (76.6%) out of 77 impalpable testes, the spermatic vessels and vas
      deferens were noted to enter the internal inguinal ring. In 41 of the 59 cases
      (69.5%), the cord structures were observed to move inferiorly when the scrotum
      was pulled downwards. In these cases, a scrotal incision was carried out first.
      In 97% (40/41), a nubbin testis was found and was then excised. In 23% (18/59),
      the cord structures did not move on pulling the scrotum, and an inguinal approach
      was initially carried out on these cases. A viable testis was found on the
      inguinal canal in four cases, and a nubbin testis was excised in 14 cases.
      CONCLUSIONS: In patients with impalpable testis undergoing diagnostic
      laparoscopy, identification of spermatic cord movement along the internal
      inguinal ring while pulling the scrotum downwards determines the most appropriate
      surgical approach. This maneuver might also prevent inappropriately placed skin
      incisions.

PMID- 25586419
TI  - The M2 muscarinic receptors are essential for signaling in the heart left
      ventricle during restraint stress in mice.
AB  - We hypothesized that muscarinic receptors (MRs) in the heart have a role in
      stress responses and thus investigated changes in MR signaling (gene expression,
      number of receptors, adenylyl cyclase (AC), phospholipase C (PLC), protein kinase
      A and C (PKA and PKC) and nitric oxide synthase [NOS]) in the left ventricle,
      together with telemetric measurement of heart rate (HR) in mice (wild type [WT]
      and M2 knockout [KO]) during and after one (1R) or seven sessions (7R) of
      restraint stress (seven mice per group). Stress decreased M2 MR mRNA and cell
      surface MR in the left ventricle in WT mice. In KO mice, 1R, but not 7R,
      decreased surface MR. Similarly, AC activity was decreased in WT mice after 1R
      and 7R, whereas in KO mice, there was no change. PLC activity was also decreased
      after 1R in WT and KO mice. This is in accord with the concept that cAMP is a key
      player in HR regulation. No change was found with stress in NOS activity. Amount
      of AC and PKA protein was not changed, but was altered for PKC isoenzymes
      (PKCalpha, beta, gamma, eta and epsilon (increased) in KO mice, and PKCiota
      (increased) in WT mice). KO mice were more susceptible to stress as shown by
      inability to compensate HR during 120 min following repeated stress. The results
      imply that not only M2 but also M3 are involved in stress signaling and in
      allostasis. We conclude that for a normal stress response, the expression of M2
      MR to mediate vagal responses is essential. 

PMID- 25586420
TI  - Is there any role for stereotactic body radiotherapy in the management of
      metastatic epidural spinal cord compression?

PMID- 25586421
TI  - A selected review of abstracts from the 11th Congress of the European Association
      of Neuro-Oncology (EANO).
AB  - The European Association of Neuro-Oncology (EANO) is the largest neuro-oncology
      meeting in Europe that meets biannually and reproducibly provides an exciting
      forum to present new brain cancer clinical trials and research data. The EANO
      2014 meeting in Turin, Italy (9-12 October 2014) was comprised of 3 days of
      presentation, nearly 50 oral presentations and nearly 350 abstracts provides a
      contemporary overview of neuro-oncology that includes both metastatic diseases of
      the CNS as well as primary brain tumors. This summary attempts to highlight
      select abstracts presented at the meeting of EANO 2014 in a short review that
      provides a portrait of a large and multifaceted meeting.

PMID- 25586422
TI  - Psychometric validation of the Brain Symptom and Impact Questionnaire (BASIQ)
      version 1.0 to assess quality of life in patients with brain metastases.
AB  - OBJECTIVE: To test the reliability, clinical and psychometric validity of the
      Brain Symptom and Impact Questionnaire (BASIQ) in patients with brain metastases.
      METHODS: Brain metastases patients were interviewed using the BASIQ, Functional
      Assessment of Cancer-Brain (FACT-Br) and FACT-General (FACT-G) at baseline, with
      a follow-up assessment at 1 month. RESULTS: Forty patients had complete one data
      and the median age was 64 years. Patients with higher KPS, ECOG of 2, primary
      breast cancer, or >3 brain metastases, scored higher on the symptom scale of the
      BASIQ. All subscales showed no significant change in patient symptoms from
      baseline to follow-up. CONCLUSION: This study supports that the reliability,
      clinical and psychometric validity of BASIQ to be used in brain metastases
      patients.

PMID- 25586423
TI  - Acute hypoxia induces upregulation of microRNA-210 expression in glioblastoma
      spheroids.
AB  - AIM: Tumor hypoxia and presence of tumor stem cells are related to therapeutic
      resistance and tumorigenicity in glioblastomas. The aim of the present study was
      therefore to identify microRNAs deregulated in acute hypoxia and to identify
      possible associated changes in stem cell markers. MATERIALS & METHODS:
      Glioblastoma spheroid cultures were grown in either 2 or 21% oxygen.
      Subsequently, miRNA profiling was performed and expression of ten stem cell
      markers was examined. RESULTS: MiRNA-210 was significantly upregulated in hypoxia
      in patient-derived spheroids. The stem cell markers displayed a complex
      regulatory pattern. CONCLUSION: MiRNA-210 appears to be upregulated in hypoxia in
      immature glioblastoma cells. This miRNA may represent a therapeutic target
      although it is not clear from the results whether this miRNA may be related to
      specific cancer stem cell functions.

PMID- 25586424
TI  - Brain metastases: an overview.
AB  - So far brain metastases represent a critical stage of a disease course and the
      frequency is increasing over the years. The treatment of brain metastases should
      be individualized for each patient: in case of single brain metastasis, surgery
      or radiosurgery should be considered as first options of treatment; in case of
      multiple lesions, whole-brain radiotherapy is the standard of care in association
      with systemic therapy or surgery/radiosurgery. Chemotherapy should be considered
      when surgery or radiation therapy are not possible. In the last decades, TKIs or
      monoclonal antibodies have shown increase in overall response rate and overall
      survival in Phase II-III trials. The aim of this paper is to make an overview of
      the current approaches in management of patients with brain metastases.

PMID- 25586425
TI  - Assessing MGMT methylation status and its current impact on treatment in
      glioblastoma.
AB  - MGMT promoter methylation status is a strong and independent prognostic factor in
      patients with newly diagnosed glioblastoma and a clinically relevant predictive
      marker in the subpopulation of elderly glioblastoma patients. However, there is
      still lack of consensus on the optimal assay for reliable MGMT promoter
      methylation testing and a variety of test are being used in different
      laboratories. Pyrosequencing is the only method for which an adequately high
      analytical performance (high intra- and interlaboratory repeatability and
      reproducibility) has been demonstrated in a fully published ring trial. For
      clinical decision-making MGMT promoter methylation testing should be performed
      only in experienced laboratories using meticulous validation of assay accuracy.
      Ideally, such laboratories should undergo regular accreditation through a quality
      control consortium.

PMID- 25586426
TI  - Migraine in a pediatric population: a clinical study in children younger than 7
      years of age.
AB  - AIM: Migraines in children younger than 7 years of age have received limited
      attention in the published literature. The aim of this study is to describe the
      characteristics of migraine phenotypes in children younger than 7 years, and to
      compare them with migraines in children older than 7 years of age. METHOD: We
      reviewed all standard clinical files, collected over 4 years, related to children
      with a diagnosis of primary headache. We included all children younger than 7
      years diagnosed with migraine in our study. RESULTS: A total of 374 children (188
      males, 186 females) were affected by migraine with/without aura: 40 of these
      patients (10.7%; 20 males, 20 females; mean age 5y 7mo, SD 1y 2mo) where younger
      than 7 years old. The frequencies of the main migraine features in the younger
      age group were similar to those of children older than 7 years, with the
      exception of a shorter duration of migraine and reduced frequency of attacks.
      INTERPRETATION: In children younger than 7 years of age, the clinical phenotype
      of migraine is similar to that seen in older children. We propose that there is a
      general genetic migraine susceptibility that, in the presence of activating
      environmental factors, may induce typical attacks of migraine in individuals
      already predisposed to migraine attacks. Therefore, different modules induce
      different clinical features within the different age groups, but there is no
      difference in the frequencies of clinical phenotypes between the two age groups.

PMID- 25586427
TI  - Ewing sarcoma: a tough road to clinically relevant biomarkers.

PMID- 25586428
TI  - Hypoxia-inducible adrenomedullin ameliorates the epithelial-to-mesenchymal
      transition in human proximal tubular epithelial cells.
AB  - Renal tubular epithelial cells can enter the epithelial-to-mesenchymal transition
      (EMT) in response to chronic hypoxia. EMT is a process which involves the
      phenotypic conversion of epithelial cells, that is believed to have an important
      role in renal fibrosis. However, the underlying mechanisms of the involvement of
      EMT in renal fibrosis remain to be elucidated. Adrenomedullin (AMD) has been
      implicated in renal fibrosis and is induced by hypoxia. The aims of the present
      study were to determine whether ADM signaling was active in human proximal
      tubular epithelial cells cultured under hypoxic conditions, and to observe the
      activity of ADM during EMT. The expression levels of ADM were significantly
      increased, in a time-dependent manner, in HK-2 and HKC human proximal tubular
      epithelial cells, cultured under hypoxic conditions. Overexpression of exogenous
      ADM was accompanied by increased expression levels of the epithelial markers E
      cadherin and tight junction protein-1, and decreased expression levels of the
      mesenchymal markers vimentin and alpha-smooth muscle actin, during hypoxia. Knock
      down of ADM expression by small hairpin RNA, or co-administration of an ADM
      peptide inhibitor, in HK-2 cells significantly exacerbated hypoxia-induced EMT,
      as compared to the lack of effect observed in the untransfected controls. ADM was
      shown to suppress EMT by inhibiting the activation of extracellular signal
      regulated kinase (ERK), and this effect was prevented by the ERK activator
      apigenin. The results of the present study suggest that ADM has an important role
      in promoting EMT in hypoxic human proximal tubular epithelial cells. ADM may
      therefore represent a novel therapeutic target in the treatment of injured
      kidneys.

PMID- 25586429
TI  - Dark-field X-ray microscopy for multiscale structural characterization.
AB  - Many physical and mechanical properties of crystalline materials depend strongly
      on their internal structure, which is typically organized into grains and domains
      on several length scales. Here we present dark-field X-ray microscopy; a non
      destructive microscopy technique for the three-dimensional mapping of
      orientations and stresses on lengths scales from 100 nm to 1 mm within embedded
      sampling volumes. The technique, which allows 'zooming' in and out in both direct
      and angular space, is demonstrated by an annealing study of plastically deformed
      aluminium. Facilitating the direct study of the interactions between crystalline
      elements is a key step towards the formulation and validation of multiscale
      models that account for the entire heterogeneity of a material. Furthermore, dark
      field X-ray microscopy is well suited to applied topics, where the structural
      evolution of internal nanoscale elements (for example, positioned at interfaces)
      is crucial to the performance and lifetime of macro-scale devices and components
      thereof.

PMID- 25586430
TI  - [In domestic violence society is often powerless].

PMID- 25586431
TI  - [Therapy of metastatic colorectal carcinoma exemplified in metachronous liver
      metastases].

PMID- 25586434
TI  - [Examining victims of interpersonal violence].
AB  - Interpersonal violence represents a widespread phenomenon with a high prevalence.
      Consequences of these acts of violence are serious and extensive to the victims
      and from a socio-economic point of view. Physical examination of the victims is a
      key aspect in the medic-legal expertise. This article describes the basic
      principles and the standard procedures in conjunction with the examination of
      violent crime victims. 

PMID- 25586436
TI  - [Tapering off is the most effective measure for protein pump inhibitor
      discontinuation].

PMID- 25586435
TI  - [Rare diagnosis as the etiology of abdominal pain after cholecystectomy].
AB  - We report a case of a 77-year old female patient with abdominal pain in the upper
      right part. In the computertomography we had the suspicion of a rare small bowel
      diverticulitis which was confirmed in laparoscopic and histopathologic
      diagnostics. After surgical excision the patient was free of symptoms. 

PMID- 25586437
TI  - [Fecal calprotectin assessment cut-offs as outcome measures or screening tool in
      inflammatory bowel disease].

PMID- 25586439
TI  - [CME-ORL. Cystic metastasis of a squamous epithelial carcinoma stage III on the
      right].

PMID- 25586441
TI  - [Personalities in the history of medicine. Ludwig Edinger].

PMID- 25586442
TI  - Identification of a novel carbohydrate esterase from Bjerkandera adusta:
      structural and function predictions through bioinformatics analysis and molecular
      modeling.
AB  - A new gene from Bjerkandera adusta strain UAMH 8258 encoding a carbohydrate
      esterase (designated as BacesI) was isolated and expressed in Pichia pastoris.
      The gene had an open reading frame of 1410 bp encoding a polypeptide of 470 amino
      acid residues, the first 18 serving as a secretion signal peptide. Homology and
      phylogenetic analyses showed that BaCesI belongs to carbohydrate esterases family
      4. Three-dimensional modeling of the protein and normal mode analysis revealed a
      breathing mode of the active site that could be relevant for esterase activity.
      Furthermore, the overall negative electrostatic potential of this enzyme suggests
      that it degrades neutral substrates and will not act on negative substrates such
      as peptidoglycan or p-nitrophenol derivatives. The enzyme shows a specific
      activity of 1.118 U mg(-1) protein on 2-naphthyl acetate. No activity was
      detected on p-nitrophenol derivatives as proposed from the electrostatic
      potential data. The deacetylation activity of the recombinant BaCesI was
      confirmed by measuring the release of acetic acid from several substrates,
      including oat xylan, shrimp shell chitin, N-acetylglucosamine, and natural
      substrates such as sugar cane bagasse and grass. This makes the protein very
      interesting for the biofuels production industry from lignocellulosic materials
      and for the production of chitosan from chitin.

PMID- 25586443
TI  - Geriatric patients with known acute kidney injury and normal renal function at
      the time of admittance to the intensive care unit/assessment of RRT requirement
      and mortality: retrospective case-control study.
AB  - BACKGROUND: The objective of our study was to investigate the renal functions on
      admittance, chronic disease status, the diagnosis on admittance to the intensive
      care unit (ICU), need for mechanical ventilation and medication groups and their
      impact over mortality and renal replacement treatment (RRT) requirement in
      geriatric patients with and without known acute kidney injury (AKI) at the time
      of admittance. METHODS: A total of 168 patients over 65 years of age having been
      monitored for more than 24 h in our Respiratory ICU and were assessed
      retrospectively. Factors influencing the RRT requirement and the mortality rates
      of patients with known AKI and normal renal function at the time of admittance
      were reviewed. RESULTS: Of 80 patients, 8 (10 %) without AKI at the time of
      admittance to the ICU required RRT during the follow-up, however, 72 of those (90
      %) completed the follow-up without developing AKI. Of 88 patients, 29 (33 %) with
      AKI at the time of admittance to the ICU required RRT, however, 59 of those (67
      %) completed the follow-up without any need for RRT. CONCLUSIONS: Presence of
      known AKI in the geriatric population at the time of their admittance to the
      respiratory ICU remarkably increased both the need for RRT and the mortality with
      respect to the geriatric population with normal renal functions. After having
      assessed the reasons justifying RRT and increasing the mortality during the
      intensive care, gastrointestinal bleeding and hypotension which necessitate the
      combined use of dopamine and noradrenaline were concluded to be prominent.

PMID- 25586445
TI  - Meandering right pulmonary vein associated with retrocaval ureter and vertebral
      fusion anomalies.
AB  - We present multimodality imaging of a meandering right pulmonary vein in a 29
      year-old female patient. It was associated with right retrocaval ureter causing
      hydronephrosis and stone formation, vertebral fusion anomalies and corrected
      cardiac anomalies (patent ductus arteriosus and ventricular septal defect). To
      the best of our knowledge, only a few meandering right pulmonary vein have been
      presented in the literature until now and this is the first reported case that is
      associated with retrocaval ureter and vertebral fusion anomalies.

PMID- 25586444
TI  - Comparison of diagnostic values of procalcitonin, C-reactive protein and blood
      neutrophil/lymphocyte ratio levels in predicting bacterial infection in
      hospitalized patients with acute exacerbations of COPD.
AB  - BACKGROUND: Viral or bacterial upper respiratory infections are the most common
      cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
      Based on available data, no reliable parameter has been presented to distinguish
      between bacterial and nonbacterial exacerbations. Therefore, we compared the
      diagnostic value of procalcitonin (PCT) level, which is a newer marker for
      predicting bacterial infections in patients with AECOPD, to routine parameters
      such as C-reactive protein (CRP) levels and the neutrophil/lymphocyte (N/L)
      ratio. METHODS: This study included all consecutive patients who were admitted
      for a diagnosis of AECOPD between January 1 and March 31, 2014. PCT, CRP, and the
      N/L ratio were assessed in addition to cultures from tracheal aspirates or sputum
      on the first day of admission. Patients with a pneumonic infiltration on chest
      radiographs, or an extrapulmonary infection focus, or whose blood samples were
      not obtained for PCT and/or CRP at the same time as sputum culture were excluded
      from the study. RESULTS: A total of 77 patients were included with a mean age of
      71.7 +/- 9.5 years. Bacteria were isolated in 37.4 % of the patients. Mean PCT
      levels were significantly higher in patients with positive sputum cultures than
      in patients with negative sputum cultures. The cut-off values for PCT, CRP, and
      the N/L ratio for predicting a bacterial infection were 0.40 ng/mL, 91.50 mg/L,
      and 11.5, respectively; sensitivity was 61, 54, and 61 % respectively;
      specificity was 67, 52, and 58 %, respectively; and the area under the curve
      (AUC) values were 0.64, 0.52, and 0.58, respectively. The AUC value of PCT was
      significantly better for predicting bacterial infection compared with the CRP
      level or the N/L ratio (p = 0.042). CONCLUSION: PCT was better than CRP and the
      N/L ratio for predicting a bacterial infection in hospitalized patients with
      AECOPD. However, we find PCT not so reliable in predicting bacterial infection in
      AECOPD due to sensitivity and specificity of less than 80 % and a low AUC value.

PMID- 25586446
TI  - Repeated sugammadex usage in a patient with multiple sclerosis: a case report.
AB  - A 42-year-old woman been suffering from multiple sclerosis for 2 years received
      an emergency laparotomy because of acute pancreatitis. Anesthesia was induced
      with propofol and fentanil and maintained with nitrous oxide and sevoflurane.
      Rocuronium was used for tracheal intubation and muscle relaxation. Train of four
      ratio was monitored for tracing muscle relaxation. Three days later the patient
      was operated again due to abdominal cavity infection and followed up with "open
      abdomen strategy" receiving general anesthesia with 3 days intervals. In all of
      the six general anesthesia procedures in 18 days the patient was successfully
      reversed with sugammadex. 

PMID- 25586447
TI  - Oral primary localized amyloidosis in HIV-infected patients: the oral face of a
      described skin lesion.
AB  - Oral primary localized amyloidosis should be considered in the diagnosis of oral
      white lesions such as hyperplastic candidosis, lichen planus and lichenoid
      reactions; it is not associated with antiretroviral therapy use, systemic
      involvement or malignant transformation. 

PMID- 25586448
TI  - Impact of nuclear factor-kappaB on restoration of neuron growth and
      differentiation in hippocampus of degenerative brain.
AB  - The mode of action of nuclear factor-kappaB (NF-kappaB) has been extensively
      observed in different aspects of cell growth and proliferation. The transcription
      factor regulates various genes controlling inflammation and anti-inflammatory
      responses in different tissues. Thus, NF-kappaB signal gains a therapeutic
      prospect. The activation of NF-kappaB requires nuclear localization of its p65
      subunit. Research also indicates an impact of phosphorylated p65 on the
      transcription of genes during cell growth and the immune response. Following the
      trends in investigations over decades, different observations suggest that NF
      kappaB activation and phosphorylation of p65 regulate neuronal plasticity. Also,
      inhibition of NF-kappaB activation is a well-demonstrated way to attenuate
      inflammation. In addition to anti-inflammatory drugs, recent researches unwind a
      way to regulate regeneration and repair tissue damage. Thus, keeping a critical
      view on NF-kappaB signals, we propose the importance of natural or synthetic NF
      kappaB activators for neurogenesis.

PMID- 25586449
TI  - Immunoglobulin G replacement for the treatment of infective complications of
      rituximab-associated hypogammaglobulinemia in autoimmune disease: a case series.
AB  - The anti-CD20 B cell depleting monoclonal antibody rituximab is being used
      increasingly for autoimmune diseases, including patients with refractory disease
      with extensive prior exposure to immunosuppressive treatments. Rituximab, in this
      context, may be associated with increased risk of adverse effects, in particular
      hypogammaglobulinemia which predisposes to recurrent infections necessitating
      Immunoglobulin G replacement. Outcome data following Immunoglobulin G replacement
      after rituximab in patients with autoimmune disease are limited. We conducted a
      retrospective study in a tertiary referral lupus and vasculitis clinic of 288
      patients who received rituximab. Clinical details of patients prescribed IgG
      replacement therapy following rituximab treatment were reviewed. We identified 12
      patients with autoimmune disease, 10/12 with systemic vasculitis, received IgG
      replacement for the treatment of recurrent infections in the context of
      persistent moderate or severe hypogammaglobulinemia following rituximab. We
      observed a range of ages (16-67 years), rituximab dosages (2-15.8 g), previous
      immunosuppression (median 3.5 non-glucocorticoid agents) and duration of disease
      (2-228 months). Six continued to receive rituximab alongside IgG replacement
      therapy to maintain disease control. IgG replacement appeared to decrease the
      incidence and severity of infections, and recovery of IgG concentrations allowed
      cessation of IgG replacement in two patients after 4 and 7.5 years of treatment.
      IgG monitoring is useful for patients receiving rituximab. IgG replacement for
      sustained hypogammaglobulinemia with recurrent infections appeared to be useful
      in this series. The IgG replacement course is prolonged in most patients, but IgG
      recovery is reported. 

PMID- 25586451
TI  - A resource for those preparing for and responding to natural disasters,
      humanitarian crises, and major healthcare emergencies.
AB  - This article describes the dissemination and knowledge transfer activities of
      Evidence Aid, which was established after the Indian Ocean tsunami of December
      2004 to provide a single source of evidence that would help people make well
      informed decisions when preparing for and responding to disasters. Evidence Aid
      has a dedicated website (www.EvidenceAid.org) to provide access to more than 160
      systematic reviews and several other documents relevant to people working on
      disaster risk reduction, planning, response, recovery, rehabilitation, and
      resilience. It combines this with a social media presence and Special Collections
      that bundle together related Cochrane Reviews (www.TheCochraneLibrary.com). The
      aim is to make it easier for users who need this evidence and don't have time to
      browse through multiple documents and distill them before making their decisions.
      Evidence Aid will continue to identify and share resources and knowledge with
      those who most need it at the time that they need it most. It is working with
      several partners to identify relevant Cochrane and non-Cochrane systematic
      reviews and is engaging with users who, by sharing their information and their
      knowledge needs, will allow Evidence Aid to target its efforts to these priority
      areas. 

PMID- 25586452
TI  - The need for evidence-based public health response in disasters.
AB  - AIM: Broad outline of this paper was presented at the Evidence Aid Symposium, on
      20 Sep 2014, at Hyderabad, India, before the 22nd Cochrane Colloquium. METHODS:
      Survey of the field and review of literature. RESULTS: Response to disasters is
      usually vulnerable to myths and misconceptions. Effective healthcare response
      requires evidence and information to meet various and often unpredictable
      eventualities. The knowledge base should facilitate rapid assessment of adverse
      health outcomes, availability healthcare infrastructure, appropriate
      organizational strategies, and selection of feasible medical interventions to
      deal with any given disaster. Most rapid surveys have to adopt some
      stratification and a cluster sampling design for representativeness. Qualitative
      research methods are useful to study organizational challenges. Adequate and
      accurate description of the context is important for interpretation of
      organization behavior studies. Testing efficacy of medical interventions by
      randomized trials is usually difficult, unless feasible study designs are planned
      in advance and ready for execution at short notice. A lot of disaster healthcare
      research literature is based on surveys and case studies, as these are more
      feasible. Hence, systematic reviews ought to rate the level of evidence from
      qualitative studies and adequately summarize the context of case studies.
      CONCLUSIONS: Research on health response to disaster has picked up momentum only
      recently in the 21(st) century. There is also a need to develop disaster
      healthcare research capacities to address regional vulnerabilities. Generating
      evidence is not enough. Concerted societal action is needed to sensitize, train,
      and equip adequate human resources to fill in various key emergency medical and
      public health roles when disaster strikes.

PMID- 25586453
TI  - Minimum initial service package (MISP) for sexual and reproductive health in
      disasters.
AB  - BACKGROUND: This paper is based on a presentation given at the Evidence Aid
      Symposium, on 20 September 2014, at Hyderabad, India. The paper provides
      background about how the sexual and reproductive health (SRH) got conceived as a
      humanitarian health response that adopts human right approach, based on core
      principles driven by needs of adolescent girls and women, and having respect for
      their values, ethics and morals. METHODOLOGY: Good practices across nations
      documented by Inter-Agency Working Groups (IAWGs) on Reproductive Health in
      Humanitarian Crisis has supported the provision of essential SRH care services to
      adolescent girls and women in humanitarian crisis and in disasters. Secondary
      desk review is used to document the lessons learnt and good practices followed
      and documents for SRH. OBJECTIVE: These essential SRH care services are to be
      provided as "Minimum Initial Service Package (MISP)" for implementation at the
      outset of disaster. The Sphere Humanitarian Charter and Minimum Standards in
      Disaster Response incorporated the MISP for SRH as a minimum standard of care in
      disaster response with a goal to reduce mortality, morbidity and disability among
      populations affected by crises, particularly women and girls. Disaster prone
      countries are expected to roll out MISP to improve humanitarian response and
      emergency preparedness systems. RESULT: The East Europe and Central Asia (EECA)
      region including India have rolled out MISP starting from 2011 (EECA) and from
      2013-2014 onwards in India across cities such as Chennai, Patna, Bhubaneshwar,
      Kolkata, Faridabad and Calcutta. Across India, through these national and state
      level trainings, nearly 600 people from NGOs, institutions, and government
      agencies were developed as national level trainers and resource persons for MISP
      who could advocate for RH in emergencies, apply core techniques provided in the
      MISP, apply coordination skills for the implementation of MISP and develop an
      action plan to integrate RH and Gender Based Violence (GBV) into Disaster
      Management Plans of respective agencies. CONCLUSION: The way forward includes
      focusing on MISP distance learning module, integration of MISP in Health action
      plans, and integration into national disaster preparedness and contingency
      planning of respective agencies and departments and building capacity at various
      levels.

PMID- 25586454
TI  - Representation of women as editors in the Cochrane collaboration.
AB  - OBJECTIVES: There is considerable gender disparity in editorial boards of medical
      journals. Being an editor in a Cochrane review group (CRG), like being an editor
      in a medical journal, is an indirect representation of one's reputation and
      leadership abilities in a particular specialty. The aim of the study was to
      analyze the representation of women editors on the editorial teams of CRG's and
      the Central Editorial Unit (CEU) of the Cochrane Collaboration. METHODS:
      Information about editorial team members of CRGs and the CEU was extracted from
      respective websites. Gender of the individual was determined by inspection of
      names, individual profile description or photographs in the CRG or institutional
      webpage, social networking sites and internet search. Data was validated by two
      authors independently and differences sorted by consensus. RESULTS: A total of
      788 editors across all CRGs and the CEU with an overall 371 females (47.1%) and
      417 (52.9%) males were identified. of the CEU editors, 62.5% were females. There
      were 68 coordinating editors (35.3% females), and 62 managing editors (56%
      females), who provided leadership to the CRGs. Eighty-four percent of trial
      search coordinators were found to be females. Ten CRGs had 75% or more of its
      editors as females while 7 CRGs had less than or equal to 25% female editors.
      CONCLUSIONS: The representation of women editors in the Cochrane Collaboration
      was found to be better than in editorial boards of medical journals. There is
      still scope for improvement to ensure better gender diversity across all roles
      and in all CRG's.

PMID- 25586455
TI  - Evaluation of organizational support for use of online information resources in
      nursing care.
AB  - OBJECTIVES: While there is general agreement concerning the barriers to use
      online information resources in nursing decisions, there have not been any
      studies that demonstrate how healthcare organizations have overcome these
      obstacles in developing countries. The purpose of this present study was to
      evaluate organizational support of healthcare organizations after introducing
      information technology for the use of online information resources in nursing
      care. METHODS: This study was performed on nurses and nursing students in
      hospitals affiliated to the Semnan University of Medical Sciences, Iran. RESULTS:
      The findings showed that the use of online information resources was not
      adequately supported by healthcare social networks and the role of leadership has
      received minimal attention. CONCLUSIONS: There appears to be little confidence in
      the usefulness of evidence-based practice (EBP) in nursing care in Iranian
      society. The development of organizational norms for EBP behavior within an
      organization is important, and in order to monitor the development of these
      behaviors, the cultural competence in the healthcare institutions should be
      assessed and measured. However, it is far more difficult to develop a robust
      design, which encompasses the implementation of EBP across an entire
      organization. Such studies are highly complex and would need to be adapted as the
      organization changed, in addition, they would be likely to take considerable time
      to complete. Nevertheless, such studies are essential if a full understanding of
      organizational approaches to promoting EBP in developing countries is to occur.

PMID- 25586456
TI  - Reduction of preanalytical errors in laboratory by establishment and application
      of training system.
AB  - OBJECTIVES: Errors in preanalytical phase occupied for almost half of total
      errors in clinical laboratory, and the causes are related to medical staff's
      quality awareness and behaviors. In order to reduce the preanalytical errors in
      our hospital, we established and applied a training system to improve the
      situation. METHODS: The disqualified sample types and major causes of errors in
      the preanalytical phase were investigated in clinical laboratory department from
      September 2008 to August 2009. In the following year, we established and applied
      a training system to affect the quality awareness and behaviors of medical staff.
      Questionnaire investigation was analyzed to illustrate the changes of
      respondents' quality awareness and behavior, and the preanalytical errors were
      reanalyzed according to different departments to evaluate the effects of the
      intervention measures. RESULTS: The total disqualification rate in the
      preanalytical phase obtained from September 2008 to August 2009 was 1.36%, and
      the major types of disqualified samples were coagulation of anticoagulant sample,
      sample inadequacy, sample container error, sample information error, and sample
      type error. After application of established training system, respondents'
      quality awareness on preanalytical samples changed dominantly, and respondents'
      own behavior and behavior to others also changed notably. The total
      disqualification rate in preanalytical phase dropped to 0.94%, among 33 clinical
      departments, the preanalytical errors in 25 departments decreased to various
      degrees, and 10 departments had overall decreasing amplitude over 50%.
      CONCLUSIONS: The overall effect of the application of established training system
      is very good, and the disqualification rate of the major departments decrease to
      various degrees.

PMID- 25586457
TI  - The G894t, T-786c and 4b/a polymorphisms in Enos gene and cancer risk: a meta
      analysis.
AB  - OBJECTIVE: Published results on association between eNOS polymorphisms and cancer
      risk are conflicting. We aimed to investigate the association and give an overall
      understanding of possible risk role of eNOS. METHOD: We searched PubMed and
      EMbase databases. The pooled ORs and 95% CIs for the association between eNOS
      polymorphisms and cancer risk was estimated using fixed- or random- effect model.
      Subgroup and sensitivity analyses were employed for further analysis. RESULTS:
      The Overall results showed no significant association of G894T polymorphism with
      cancer susceptibility (T vs. G: OR 1.02, 95% CI 0.97 to 1.07; TT+GT vs. GG: OR
      1.02, 95% CI 0.96 to 1.09; TT vs. GT+GG: OR 1.05, 95% CI 0.93 to 1.17). For the T
      786C polymorphism, pooled OR under recessive model suggested that CC genotype was
      significantly associated with increased cancer risk (CC vs. TC+TT: OR 1.31, 95%
      CI 1.09 to 1.57). For the 4b/a polymorphism, pooled OR for recessive model
      suggested positive result of 4a/4a genotype (aa vs. ba+bb: OR 1.64, 95% CI 1.11
      to 2.43). In subgroup analysis by ethnicity, significant association was found in
      Caucasians in recessive model but not in Asians for T-786C and 4b/a,
      respectively. In subgroup analysis by cancer types, significant result was
      obtained for breast cancer in recessive model for the T-786C polymorphism.
      CONCLUSION: The eNOS G894T polymorphism may not be a major risk factor for most
      types of cancers. The CC of T-786C polymorphism and 4a/4a of 4b/a polymorphism
      are associated with cancer risk, especially in Caucasians. There is significant
      association between T786C polymorphism and breast cancer risk. More data are
      needed to verify these results.

PMID- 25586458
TI  - High-intensity focused ultrasound for treatment of pancreatic cancer: a
      systematic review.
AB  - OBJECTIVE: To explore the efficacy and safety of high-intensity focused
      ultrasound combined with other physical therapies for the treatment of pancreatic
      cancer, so as to provide reference for clinical application. METHODS: The PubMed,
      EMbase, The Cochrane Library (Issue 11, 2013), CBM, CNKI, and WanFang databases
      were systematically searched up to November 2013. The randomized controlled
      trials and clinical controlled trials about the treatment of high-intensity
      focused ultrasound were included. According to the inclusion and exclusion
      criteria, two reviewers independently screened the studies, exacted the data, and
      assessed the quality. The meta-analysis was performed by using the RevMan 5.0
      software. RESULTS: A total of 23 studies including 19 randomized controlled
      trials and four clinical controlled trials were included. Of which 14 studies
      reported the safety. The results of meta-analyses showed that: the survival rate
      at 6 months and 12 months, overall efficacy, and clinical benefit rate in high
      intensity focused ultrasound plus radiation and chemotherapy group were
      significantly higher than those in groups treated with three-dimensional
      conformal radiation therapy (P < 0.05), gemcitabine (P < 0.05), gemcitabine plus
      cisplatin (P < 0.05), and gemcitabine plus 5-fluorouracil (P < 0.05). The adverse
      effect caused by high-intensity focused ultrasound plus other therapy was equal
      to those in the control group. The major high-intensity focused ultrasound
      related adverse effect was skin damage and fever. CONCLUSION: The current
      evidence suggested that the efficacy of high-intensity focused ultrasound for
      pancreatic cancer was superior to other therapies. However, the poor quality of
      trails may reduce the reliability of outcome to some extent. The current evidence
      suggested that the efficacy of HIFU for pancreatic cancer was superior to other
      therapies, but with poor quality. Therefore, a standard and unified criterion for
      the diagnosis and outcome measures of pancreatic cancer is needed, and the
      quality of study design and implementation should be bettered, so as to improve
      the high quality of evidence for its clinical application.

PMID- 25586459
TI  - Education section: Evidence Aid, in the beginning.

PMID- 25586462
TI  - Pressure-controlled versus volume-controlled ventilation for acute respiratory
      failure due to acute lung injury (ALI) or acute respiratory distress syndrome
      (ARDS).
AB  - BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS) account for one-quarter of cases of acute respiratory failure in intensive
      care units (ICUs). A third to half of patients will die in the ICU, in hospital
      or during follow-up. Mechanical ventilation of people with ALI/ARDS allows time
      for the lungs to heal, but ventilation is invasive and can result in lung injury.
      It is uncertain whether ventilator-related injury would be reduced if pressure
      delivered by the ventilator with each breath is controlled, or whether the volume
      of air delivered by each breath is limited. OBJECTIVES: To compare pressure
      controlled ventilation (PCV) versus volume-controlled ventilation (VCV) in adults
      with ALI/ARDS to determine whether PCV reduces in-hospital mortality and
      morbidity in intubated and ventilated adults. SEARCH METHODS: In October 2014, we
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014,
      Isssue 9), MEDLINE (1950 to 1 October 2014), EMBASE (1980 to 1 October 2014), the
      Latin American Caribbean Health Sciences Literature (LILACS) (1994 to 1 October
      2014) and Science Citation Index-Expanded (SCI-EXPANDED) at the Institute for
      Scientific Information (ISI) Web of Science (1990 to 1 October 2014), as well as
      regional databases, clinical trials registries, conference proceedings and
      reference lists. SELECTION CRITERIA: Randomized controlled trials (RCTs) and
      quasi-RCTs (irrespective of language or publication status) of adults with a
      diagnosis of acute respiratory failure or acute on chronic respiratory failure
      and fulfilling the criteria for ALI/ARDS as defined by the American-European
      Consensus Conference who were admitted to an ICU for invasive mechanical
      ventilation, comparing pressure-controlled or pressure-controlled inverse-ratio
      ventilation, or an equivalent pressure-controlled mode (PCV), versus volume
      controlled ventilation, or an equivalent volume-controlled mode (VCV). DATA
      COLLECTION AND ANALYSIS: Two review authors independently screened and selected
      trials, assessed risk of bias and extracted data. We sought clarification from
      trial authors when needed. We pooled risk ratios (RRs) for dichotomous data and
      mean differences (MDs) for continuous data with their 95% confidence intervals
      (CIs) using a random-effects model. We assessed overall evidence quality using
      the GRADE (Grades of Recommendation, Assessment, Development and Evaluation)
      approach. MAIN RESULTS: We included three RCTs that randomly assigned a total of
      1089 participants recruited from 43 ICUs in Australia, Canada, Saudi Arabia,
      Spain and the USA. Risk of bias of the included studies was low. Only data for
      mortality and barotrauma could be combined in the meta-analysis. We downgraded
      the quality of evidence for the three mortality outcomes on the basis of serious
      imprecision around the effect estimates. For mortality in hospital, the RR with
      PCV compared with VCV was 0.83 (95% CI 0.67 to 1.02; three trials, 1089
      participants; moderate-quality evidence), and for mortality in the ICU, the RR
      with PCV compared with VCV was 0.84 (95% CI 0.71 to 0.99; two trials, 1062
      participants; moderate-quality evidence). One study provided no evidence of clear
      benefit with the ventilatory mode for mortality at 28 days (RR 0.88, 95% CI 0.73
      to 1.06; 983 participants; moderate-quality evidence). The difference in effect
      on barotrauma between PCV and VCV was uncertain as the result of imprecision and
      different co-interventions used in the studies (RR 1.24, 95% CI 0.87 to 1.77; two
      trials, 1062 participants; low-quality evidence). Data from one trial with 983
      participants for the mean duration of ventilation, and from another trial with 78
      participants for the mean number of extrapulmonary organ failures that developed
      with PCV or VCV, were skewed. None of the trials reported on infection during
      ventilation or quality of life after discharge. AUTHORS' CONCLUSIONS: Currently
      available data from RCTs are insufficient to confirm or refute whether pressure
      controlled or volume-controlled ventilation offers any advantage for people with
      acute respiratory failure due to acute lung injury or acute respiratory distress
      syndrome. More studies including a larger number of people given PCV and VCV may
      provide reliable evidence on which more firm conclusions can be based.

PMID- 25586461
TI  - Drinking experience uncovers genetic influences on  alcohol expectancies across
      adolescence.
AB  - AIMS: To test whether drinking onset moderates genetic and environmental
      contributions to individual differences in the etiology of alcohol expectancies
      across adolescence. DESIGN: Longitudinal twin design. SETTING: Community sample
      from Los Angeles, CA, USA. PARTICIPANTS: A total of 1292 male and female twins,
      aged 11-18years, were assessed at 1 (n = 440), 2 (n = 587) or 3 (n = 265)
      occasions as part of the risk factors for the Antisocial Behavior Twin Study.
      MEASUREMENTS: Social behavioral (SB) alcohol expectancies were measured using an
      abbreviated version of the Social Behavioral subscale from the Alcohol Expectancy
      Questionnaire for adolescents (AEQ-A). Drinking onset was defined as >1 full
      drink of alcohol. FINDINGS: Alcohol expectancies increased over age and the
      increase became more rapid following onset of drinking. The importance of genetic
      and environmental influences on SB scores varied with age and drinking status,
      such that variation prior to drinking onset was attributed solely to
      environmental influences, whereas all post-onset variation was attributed to
      genetic influences. Results did not differ significantly by sex. CONCLUSION: Only
      environmental factors explain beliefs about the social and behavioral
      consequences of alcohol use prior to drinking onset,whereas genetic factors
      explain an increasing proportion of the variance in these beliefs after drinking
      onset.

PMID- 25586463
TI  - Increased expression of endosomal members of toll-like receptor family abrogates
      wound healing in patients with type 2 diabetes mellitus.
AB  - The inflammatory phase of wound healing cascade is an important determinant of
      the fate of the wound. Acute inflammation is necessary to initiate proper wound
      healing, while chronic inflammation abrogates wound healing. Different endosomal
      members of toll-like receptor (TLR) family initiate inflammatory signalling via a
      range of different inflammatory mediators such as interferons, internal tissue
      damaged-associated molecular patterns (DAMPs) and hyperactive effector T cells.
      Sustained signalling of TLR9 and TLR7 contributes to chronic inflammation by
      activating the plasmacytoid dendritic cells. Diabetic wounds are also
      characterised by sustained inflammatory phase. The objective of this study was to
      analyse the differential expression of endosomal TLRs in human diabetic wounds
      compared with control wounds. We analysed the differential expression of TLR7 and
      TLR9 both at transcriptional and translational levels in wounds of 84 patients
      with type 2 diabetes mellitus (T2DM) and 6 control subjects without diabetes
      using quantitative real-time polymerase chain reaction (RT-PCR), western blot and
      immunohistochemistry. TLR7 and TLR9 were significantly up-regulated in wounds of
      the patients with T2DM compared with the controls and were dependent on the
      infection status of the diabetic wounds, and wounds with microbial infection
      exhibited lower expression levels of endosomal TLRs. Altered endosomal TLR
      expression in T2DM subjects might be associated with wound healing impairment. 

PMID- 25586464
TI  - Comparison of trajectories of self-monitored glucose levels by hypoglycemia
      status over 52 weeks of treatment with insulin glargine or exenatide once weekly.
AB  - BACKGROUND: Self-monitoring of blood glucose (SMBG) is used as a means to detect
      and prevent hypoglycemia in patients with diabetes. However, information on the
      longitudinal measures (trajectory) of SMBG-based pre- and postprandial glucose
      fluctuations over time in relation to hypoglycemia is limited. Among patients
      treated with exenatide once weekly (EQW) or insulin glargine (IG), this study
      compared SMBG profiles over 52 weeks between patients who did and did not
      experience hypoglycemia. METHODS: Pooled patient-level 52-week longitudinal data
      of treatment with EQW (n = 531) or IG (n = 219) from three controlled trials were
      analyzed. RESULTS: The proportion of patients with at least one episode of
      hypoglycemia in the EQW and IG groups was 23% and 54%, respectively. The
      preprandial glucose measures from SMBG were significantly lower among patients
      who experienced hypoglycemia in both treatment groups compared with those who did
      not. In patients who experienced hypoglycemia, the average preprandial glucose
      levels over 52 weeks were lower by 0.64 and 0.66 mmol/L in the EQW and IG groups,
      respectively (P < 0.01 in both cases) compared with those without hypoglycemia.
      The average postprandial levels were not significantly different between patients
      who did and did not experience hypoglycemia in both treatment groups. Among
      patients with hypoglycemia, the average prebreakfast glucose trajectory was
      higher by 0.48 mmol/L in the EQW compared with the IG group. CONCLUSIONS: This
      study has revealed differential trajectories of pre- and postprandial glucose
      profiles between patients with and without hypoglycemia. However, the SMBG
      trajectories were similar between patients treated with EQW and IG.

PMID- 25586465
TI  - Gastric cancer cell proliferation is suppressed by frizzled-2 short hairpin RNA.
AB  - In order to identify novel targets for the molecular therapy of gastric cancer
      (GC), we investigated the mRNA and protein expression of frizzled-2 (Fz2), a Wnt
      signaling pathway receptor. Reverse-transcriptase polymerase chain reaction (PCR)
      amplification was utilized to determine the expression patterns of Fz genes in
      normal stomach and in the GC cell lines MKN45 and MKN74. Immunostaining was
      performed on surgical specimens of GC using an antibody against Fz2. The 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H
      tetrazolium inner salt (MTS) assay was performed on MKN45 cells and MKN74 cells
      transfected with Fz2 short-hairpin (sh) RNA. Cell motility was analyzed by
      scratch assay following Fz2 shRNA. Real-time quantitative PCR was performed to
      analyze the expression levels of cyclin D1 and matrix metallopeptidase 9 (MMP-9).
      Fz1, 3, 6 and 8 were expressed in normal stomach, and in MKN45 and MKN74 cells.
      Fz2 was expressed in normal stomach and in MKN45, but not in MKN74 cells. Well
      differentiated GC tissue was weakly positive for Fz2 in cell membranes. Fz2 was
      positive in both the cell membrane and cytoplasm of GC tissues of moderately
      differentiated and poorly differentiated adenocarcinoma. Signet ring cells were
      positive for cytoplasmic Fz2. Proliferation of MKN45 and MKN74 cells was
      suppressed by Fz2 shRNA, and a scratch assay demonstrated that Fz2 shRNA
      suppressed also MKN45 and MKN74 cell motility. Furthermore, Fz2 shRNA application
      led to downregulated mRNA expression of both cyclin D1 and MMP-9. Fz2, 3, 6 and 8
      were expressed in normal stomach, and in MKN45 and MKN74 GC cells. Fz2 shRNA
      suppressed cell proliferation and motility of MKN45 and MKN74 cells, and
      downregulated cyclin D1 and MMP-9 expression in these GC cell lines.

PMID- 25586467
TI  - Complications in ankle fracture surgery.

PMID- 25586466
TI  - NLRP3 inflammasome is associated with the response to IFN-beta in patients with
      multiple sclerosis.
AB  - Evidence exists for a potential modulation of inflammasome activity by interferon
      beta. Here, we investigated the roles of inflammasomes [absent in melanoma 2
      (AIM2); NLR family, CARD domain containing 4 (NLRC4); NLR family, pyrin domain
      containing 1 and 3 (NLRP1 and NLRP3)] and related cytokines (IL1B, IL10, IL18) in
      the response to interferon beta in patients with relapsing-remitting multiple
      sclerosis. Ninety-seven patients treated with interferon beta were classified
      into responders and non-responders according to clinical criteria after 24 months
      and clinical-radiological criteria after 12 months of treatment. Messenger RNA
      expression levels of inflammasomes and cytokines were determined by real-time
      polymerase chain reaction in peripheral blood mononuclear cells collected before
      treatment with interferon beta. In a subgroup of patients, NLRP3 and IL1B
      expression was also determined after 3 months (n = 32) and 12 months (n = 20) of
      interferon beta treatment. A polymorphism located in the NLRP3 gene, rs35829419,
      was genotyped in 789 multiple sclerosis patients treated with interferon beta.
      Baseline mRNA expression levels for NLRP3 and IL1B were increased in peripheral
      blood mononuclear cells from non-responders compared to responders classified
      according to clinical criteria after 24 months (P = 0.02 and P = 0.001,
      respectively). No significant differences were observed for other inflammasomes
      and related cytokines. Differences in NLRP3 and IL1B expression remained
      significant following a clinical-radiological classification after 12 months (P =
      0.007 and P = 0.02, respectively). After treatment with interferon beta, NLRP3
      and IL1B expression was increased in responders but unchanged in non-responders.
      A trend for association was observed between rs35829419 and interferon beta
      response (pM-H = 0.08). These results point to a role of the NLRP3 inflammasome
      and its related cytokine IL1B in the response to interferon beta in patients with
      relapsing-remitting multiple sclerosis. 

PMID- 25586469
TI  - Impact of unemployment variations on suicide mortality in Western European
      countries (2000-2010): authors' reply.

PMID- 25586468
TI  - A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed
      glioblastoma: the ACT III study.
AB  - BACKGROUND: The epidermal growth factor receptor variant III deletion mutation,
      EGFRvIII, is expressed in ~30% of primary glioblastoma and linked to poor long
      term survival. Rindopepimut consists of the unique EGFRvIII peptide sequence
      conjugated to keyhole limpet hemocyanin. In previous phase II trials
      (ACTIVATE/ACT II), rindopepimut was well tolerated with robust EGFRvIII-specific
      immune responses and promising progression-free and overall survival. This
      multicenter, single-arm phase II clinical trial (ACT III) was performed to
      confirm these results. METHODS: Rindopepimut and standard adjuvant temozolomide
      chemotherapy were administered to 65 patients with newly diagnosed EGFRvIII
      expressing (EGFRvIII+) glioblastoma after gross total resection and
      chemoradiation. RESULTS: Progression-free survival at 5.5 months (~8.5 mo from
      diagnosis) was 66%. Relative to study entry, median overall survival was 21.8
      months, and 36-month overall survival was 26%. Extended rindopepimut vaccination
      (up to 3.5+ years) was well tolerated. Grades 1-2 injection site reactions were
      frequent. Anti-EGFRvIII antibody titers increased >=4-fold in 85% of patients,
      and increased with duration of treatment. EGFRvIII was eliminated in 4/6 (67%)
      tumor samples obtained after >3 months of therapy. CONCLUSIONS: This study
      confirms, in a multicenter setting, the preliminary results seen in previous
      phase II trials of rindopepimut. A pivotal, double-blind, randomized, phase III
      trial ("ACT IV") is under way.

PMID- 25586470
TI  - Treatment of Acute Hepatic Encephalopathy: Comparing the Effects of Adding
      Rifaximin to Lactulose on Patient Outcomes.
AB  - OBJECTIVES: Rifaximin is approved for the reduction of hepatic encephalopathy
      (HE) recurrence in patients with chronic liver disease (CLD); however, few
      studies have evaluated the benefit of adding rifaximin to lactulose for treatment
      of acute HE. The aim of this study was to determine the impact of combination
      therapy with lactulose and rifaximin on hospital length of stay (LOS) and
      readmission rates. METHODS: A retrospective study of patients admitted to an
      adult hospital within the Methodist LeBonheur Healthcare (MLH) System in Memphis,
      Tennessee, between 2007 and 2012 was conducted. Patients were identified via
      International Classification of Diseases, Ninth Revision (ICD-9) coding for liver
      cirrhosis. RESULTS: Of the 173 patients included, 87 (50%) received lactulose
      monotherapy and 62 (36%) combination therapy, while 24 (14%) underwent therapy
      escalation. Median LOS was 6 days in monotherapy group and 8 days in combination
      group (P = .9). At 180 days, patients receiving combination therapy had fewer
      readmissions for HE than those receiving monotherapy (2.4% vs 16.2%, P = .02).
      CONCLUSION: Addition of rifaximin to lactulose for treatment of acute HE did not
      reduce hospital LOS; however, it did result in lower readmission rates for HE at
      180 days.

PMID- 25586471
TI  - Sperm nuclear DNA fragmentation and its association with semen quality in Greek
      men.
AB  - Due to the limitations of conventional semen analysis in predicting a man's
      fertility potential, sperm DNA fragmentation was recently introduced as a novel
      marker of sperm quality. This prospective study was undertaken to investigate the
      associations between conventional seminal parameters and DNA fragmentation in
      Greek men. A total of 669 subject data were evaluated in two groups,
      normozoospermic (n = 184) and non-normozoospermic (n = 485), according to the WHO
      2010 (WHO Laboratory Manual for the Examination and Processing of Human Semen,
      5th edn. World Health Organization), reference limits. For all the subjects,
      semen volume, sperm concentration, total count, rapid and total progressive
      motility and morphology were recorded following the WHO 2010 methods and DNA
      fragmentation was assessed by the sperm chromatin dispersion assay. An inverse
      correlation was established between DNA fragmentation and all conventional
      seminal parameters except semen volume in men with seminal profiles below the
      reference limits, with statistical significance for rapid and total progressive
      motility. Normozoospermic men exhibited lower levels of DNA fragmentation than
      their non-normozoospermic counterparts, even though the values were not always
      below 30%. DNA fragmentation testing and traditional semen analysis should
      therefore be considered as complementary diagnostic tools in a comprehensive
      evaluation of male infertility.

PMID- 25586474
TI  - Reply: To PMID 25586475.

PMID- 25586472
TI  - Activating mutations of STAT5B and STAT3 in lymphomas derived from gammadelta-T
      or NK cells.
AB  - Lymphomas arising from NK or gammadelta-T cells are very aggressive diseases and
      little is known regarding their pathogenesis. Here we report frequent activating
      mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), gammadelta-T-cell
      lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger
      sequencing. STAT5B N642H is particularly frequent in all forms of gammadelta-T
      cell lymphomas. STAT3 and STAT5B mutations are associated with increased
      phosphorylated protein and a growth advantage to transduced cell lines or normal
      NK cells. Growth-promoting activity of the mutants can be partially inhibited by
      a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance
      measurements of the N642H mutant indicate a marked increase in binding affinity
      of the phosphotyrosine-Y699 with the mutant histidine. This is associated with
      the prolonged persistence of the mutant phosphoSTAT5B and marked increase of
      binding to target sites. Our findings suggest that JAK-STAT pathway inhibition
      may represent a therapeutic strategy.

PMID- 25586473
TI  - An overactive bladder online self-management program with embedded avatars: a
      randomized controlled trial of efficacy.
AB  - OBJECTIVE: To determine whether an avatar-based, online, self-management program
      is an effective therapeutic approach for women with overactive bladder (OAB). OAB
      is a highly prevalent symptom complex that significantly impacts health-related
      quality of life (HRQOL). Behavioral interventions can produce substantial
      improvement in symptoms and HRQOL. Online education programs offer patients with
      OAB an alternative to face-to-face self-management instruction. Evidence suggests
      that avatars (digital humans) embedded into online programs may help persuade and
      motivate patients to adopt healthy behaviors. METHODS: In a 12-week, randomized,
      controlled trial, women (aged >55 years) with symptoms of OAB for at least 3
      months were randomized to 2 versions of a 3-part, online, self-management
      program. After collecting the baseline metrics, the intervention group viewed a
      generic avatar coach with a self-avatar peer mentor designed to resemble the
      participant, and the control group viewed the identical online program with voice
      only. Participants viewed part 1 at week 1 and parts 2 and 3 at week 6.
      Participants completed daily bladder diaries throughout the 12-week period and
      OAB-related outcome measures at weeks 1, 6, and 12. RESULTS: Forty-one women
      completed the study (mean age = 61 years, standard deviation = 6). The analysis
      of covariance of week-12 outcome measures with the baseline as covariates
      demonstrated significant improvements in the intervention group in OAB
      questionnaire HRQOL (P = .02; large effect), 24-hour frequency (P <.001; large
      effect), night-time urination (P <.001; large effect), urgency (P <.001; large
      effect), and urge incontinence (P <.001; large effect). CONCLUSION: An avatar
      based intervention embedded into an online self-management program improved OAB
      HRQOL and symptoms in women.

PMID- 25586475
TI  - Editorial comment.

PMID- 25586476
TI  - Prevalence of high-grade or insignificant prostate cancer in Korean men with
      prostate-specific antigen levels of 3.0-4.0 ng/mL.
AB  - OBJECTIVE: To investigate the prevalence of high-grade or insignificant prostate
      cancer in Korean men with prostate-specific antigen (PSA) levels of 3.0-4.0
      ng/mL. METHODS: The medical records of 4233 consecutive men with PSA levels of
      3.0-10.0 ng/mL, who underwent prostate biopsy between 2007 and 2012 at our
      institute, were reviewed. The clinicopathologic characteristics were compared
      between patients with a PSA level of 3.0-4.0 ng/mL and those with a PSA level of
      4.0-10.0 ng/mL. Predictive factors for high-grade (Gleason score >=7) or
      insignificant cancer (defined according to the Epstein criteria) in men with a
      PSA level of 3.0-4.0 ng/mL were assessed. RESULTS: The high-grade disease rates
      were similar between men with a PSA level of 3.0-4.0 ng/mL and those with a PSA
      level of 4.0-10.0 ng/mL (50.5% and 53.1%, respectively). The rates of clinically
      insignificant cancer were higher in men with a PSA level of 3.0-4.0 ng/mL than in
      those with a PSA level of 4.0-10.0 ng/mL (28.4% vs 12.5%; P <.001). However,
      among patients with clinically insignificant cancer who underwent radical
      prostatectomy, only 20% of those with a PSA level of 3.0-4.0 ng/mL and 16% of
      those with a PSA level of 4.0-10.0 ng/mL showed pathologically insignificant
      cancer. Prostate volume was an independent predictor of high-grade disease in men
      with PSA levels of 3.0-4.0 ng/mL. CONCLUSION: More than half of the cancer
      patients had high-grade disease in men with a PSA level of 3.0-4.0 ng/mL, and
      most cases of clinically insignificant cancer were diagnosed as significant
      cancer on prostatectomy specimens, suggesting that the optimal PSA threshold for
      prostate biopsy in Korean men is 3.0 ng/mL.

PMID- 25586477
TI  - A simplified laparoscopic approach to repair vesicovaginal fistula: the M.S.
      Ramaiah technique.
AB  - OBJECTIVE: To describe a simplified laparoscopic approach for the management of
      vesicovaginal fistula (VVF), with the specific aim of decreasing laparoscopic
      intracorporeal suturing and to highlight our results with this simplified
      approach. MATERIALS AND METHODS: A retrospective chart review was carried out to
      all patients who underwent VVF repair at our institute by the "simplified
      laparoscopic approach" between January 2011 and August 2014. Preoperative
      evaluation consisted of intravenous urography, micturating cystography, and
      cystoscopy. Patients with malignant fistulas, history of pelvic irradiation, or
      co-existent ureteric fistulas were excluded. The procedure consisted of an
      initial cystoscopy to intubate bilateral ureteric orifices with ureteric
      catheter, as well as the fistula with a ureteric catheter of different color. A 3
      port technique was used. The simplified laparoscopic approach consisted of
      limited cystotomy, single-layer bladder closure with 3-0 V-Loc barbed suture and
      omental patch over the vaginal opening. RESULTS: A total of 22 patients were
      included in the analysis. Mean interval before surgery was 2.5 months. One
      patient had previous failed transvaginal repair. Transvaginal hysterectomy for
      benign uterine pathology constituted the predominant etiology of VVF in this
      series. Mean fistula size was 7 mm. Mean operative time was 75 minutes. All
      patients were continent at catheter removal at postoperative day 14 and remained
      symptom free in the follow-up period. CONCLUSION: The simplified laparoscopic
      approach of VVF repair produces excellent results with minimal morbidity.

PMID- 25586478
TI  - Cost comparison of open and robotic partial nephrectomy using a short
      postoperative pathway.
AB  - OBJECTIVE: To compare immediate perioperative direct costs of open partial
      nephrectomy (OPN) and robotic partial nephrectomy (RPN), managed under a common
      care pathway. METHODS: Retrospective review of detailed institutional cost data
      for patients treated with OPN and RPN during 2011 was conducted. Cost and
      clinical data of OPN and RPN were compared for all patients and for patients
      stratified by length of stay (LOS), American Society of Anesthesiologists (ASA),
      and RENAL nephrometry scores. RESULTS: The study cohort included 190 OPN and 63
      RPN cases. OPN was associated with higher ASA scores (P <.001), shorter operative
      times (P = .014), and higher estimated blood loss (P <.001). Median
      (interquartile range) LOS was 2 days (2-3 days) for OPN compared with 1 day (1-2
      days) for RPN (P <.001). Median perioperative cost of OPN was lower than that of
      RPN with a difference of $3091 (P <.001). Although hospitalization costs were
      higher in OPN, surgical costs were higher in RPN ($854 and $3695 difference in
      median costs, respectively; P <.001 for both). The total cost of OPN for patients
      with an above-average LOS remained lower than that of RPN ($2680 difference in
      median costs; P = .001). RPN costs remained significantly higher when stratifying
      patients by their ASA and RENAL nephrometry scores. CONCLUSION: Despite the
      shorter hospital LOS associated with RPN, the immediate perioperative cost of OPN
      was lower than that of RPN for patients managed under a common care pathway,
      mainly due to high robotic purchase and maintenance costs. In light of the
      current health care debate, such financial disincentives may compromise the
      sustainability of advances in medical technology.

PMID- 25586479
TI  - Hypolipidemic Effect and Mechanism of Palmatine from Coptis chinensis in Hamsters
      Fed High-Fat diet.
AB  - Palmatine (PAL) is one of the main alkaloids in Coptis chinensis. The present aim
      was to investigate the hypolipidemic effect and mechanism of palmatine in
      hamsters fed with high-fat diet (HFD). PAL treatment decreased serum total
      cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL
      C) levels, as well as increased fecal excretion of TC and total bile acids (TBA)
      in hyperlipidemic hamsters. Furthermore, PAL treatment up-regulated low-density
      lipoprotein receptor (LDLR) and cholesterol 7alpha-hydroxylase (CYP7A1) mRNA and
      protein expression and down-regulated apical sodium-dependent bile salt
      transporter (ASBT) mRNA and protein expression. These results demonstrated that
      PAL as a potential natural cholesterol lowering agent works by up-regulating LDLR
      and CYP7A1 mRNA and protein expression, down-regulating ASBT mRNA and protein
      expression, as well as enhancing fecal excretion of TC and TBA. The findings in
      our study suggest that palmatine could be a potential natural agent for treating
      hyperlipidemia.

PMID- 25586480
TI  - Sirolimus plus gemcitabine: a new therapeutic combination for resistant sarcomas?
AB  - Sarcomas are a rare family of heterogeneous tumors of mesenchymal origin
      characterized by their bad prognosis. In addition, limited active therapeutic
      options are available. The cytotoxic drug gemcitabine and the inhibition of the
      mTOR pathway have demonstrated modest activity in sarcomas as monotherapy.
      However, preclinical data suggest that the combination of both treatments results
      in enhanced antitumor activity. In vitro and in vivo experiments with the mTOR
      inhibitor sirolimus plus gemcitabine showed dramatic results in preclinical
      models of sarcoma. Moreover, a Phase I study demonstrated the favorable toxicity
      profile of the combination in patients with advanced solid tumors. Therefore,
      treatment with sirolimus plus gemcitabine deserves further investigation in
      sarcomas. 

PMID- 25586481
TI  - Pharmacokinetic enhancement in HIV antiretroviral therapy: a comparison of
      ritonavir and cobicistat.
AB  - Inhibition of the cytochrome p450 3A4 enzyme system leads to increases in plasma
      concentrations of coadministered antiretroviral agents - a concept known as
      pharmacokinetic boosting. Ritonavir and cobicistat are potent inhibitors of
      cytochrome p450 3A4. Ritonavir was initially developed as an HIV protease
      inhibitor, but is currently used primarily as a pharmacokinetic boosting agent
      for other HIV and hepatitis C protease inhibitors. Cobicistat is a boosting agent
      for the integrase inhibitor elvitegravir and the protease inhibitors atazanavir
      and darunavir. Phase III data showed that atazanavir + cobicistat +
      tenofovir/emtricitabine had non-inferior efficacy and resulted in similar CD4 T
      cell count increases to atazanavir + ritonavir + tenofovir/emtricitabine. The
      tolerability, gastrointestinal, and lipid profile of the cobicistat-containing
      regimen was comparable with the ritonavir-containing regimen. Primary HIV
      protease resistance mutations were not selected in either ritonavir or cobicistat
      arm virologic failures. Cobicistat-containing regimens have consistently shown
      higher serum creatinine increases and creatinine clearance decreases compared
      with ritonavir, and accurate assessment of glomerular filtration in the presence
      of cobicistat could only be made by using exogenous markers such as iohexol.
      Drugs contraindicated with cobicistat are consistent with those contraindicated
      with ritonavir-containing protease inhibitor regimens with respect to cytochrome
      p450 3A interactions. Information in this review may help clinicians assess the
      benefits and limitations of currently available pharmacokinetic enhancers when
      selecting the most appropriate treatment for their patients. 

PMID- 25586482
TI  - Propofol Attenuates Lipopolysaccharide-Induced Monocyte Chemoattractant Protein-1
      Production Through Enhancing apoM and foxa2 Expression in HepG2 Cells.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a cytokine that mediates the influx
      of cells to sites of inflammation. Our group recently reported that propofol
      exerted an anti-inflammatory effect and could inhibit lipopolysaccharide (LPS)
      induced production of pro-inflammatory cytokines. However, the effect and
      possible mechanisms of propofol on MCP-1 expression remain unclear. LPS
      stimulated HepG2 cells were treated with 50 MUM propofol for 0, 6, 12, and 24 h,
      respectively. The transcript and protein levels were measured by real-time
      quantitative PCR and Western blot analyses, respectively. We found that propofol
      markedly decreased both MCP-1 messenger RNA (mRNA) and protein levels in LPS
      stimulated HepG2 cells in a time-dependent manner. Expression of apolipoprotein M
      (apoM) and forkhead box protein A2 (foxa2) was increased by propofol treatment in
      HepG2 cells. In addition, the inhibitory effect of propofol on MCP-1 expression
      was significantly abolished by small interfering RNA against apoM and foxa2 in
      LPS-stimulated HepG2 cells. Propofol attenuates LPS-induced MCP-1 production
      through enhancing apoM and foxa2 expression in HepG2 cells. 

PMID- 25586483
TI  - GlycA is a Novel Marker of Inflammation Among Non-Critically Ill Hospitalized
      Patients with Type 2 Diabetes.
AB  - GlycA is a nuclear magnetic resonance-derived signal that originates from
      oligosaccharide chains of acute phase proteins. The objective of this study is to
      characterize GlycA levels in hospitalized non-critically ill patients with type 2
      diabetes. This study evaluated traditional and novel (GlycA) inflammatory markers
      among 121 patients who were stratified by admission diagnoses: congestive heart
      failure (CHF), cardiac non-CHF (CARD), infection (INF), and other (OTH). HbA1c
      was similar across groups (8.0-9.2%, p=0.20). Inflammatory markers were elevated
      but varied significantly across disease categories, with the highest values of
      interleukin-6 (IL-6), c-reactive protein (CRP), and GlycA in the INF group and
      the highest tumor necrosis factor-alpha and intracellular adhesion molecule-1
      levels in CHF group. GlycA was associated with higher IL-6 and CRP, lower
      hemoglobin, and lower glomerular filtration rate. GlycA and other inflammatory
      markers were not significantly associated with admission glucose or HbA1c. Among
      hospitalized non-critically ill patients with type 2 diabetes, GlycA was highest
      in INF patients and was associated with IL-6 and CRP. None of the markers were
      significant predictors of glucose control.

PMID- 25586486
TI  - Proton transfer in a short hydrogen bond caused by solvation shell fluctuations:
      an ab initio MD and NMR/UV study of an (OHO)(-) bonded system.
AB  - We present a joint experimental and quantum chemical study on the influence of
      solvent dynamics on the protonation equilibrium in a strongly hydrogen bonded
      phenol-acetate complex in CD2Cl2. Particular attention is given to the
      correlation of the proton position distribution with the internal conformation of
      the complex itself and with fluctuations of the aprotic solvent. Specifically, we
      have focused on a complex formed by 4-nitrophenol and tetraalkylammonium-acetate
      in CD2Cl2. Experimentally we have used combined low-temperature (1)H and (13)C
      NMR and UV-vis spectroscopy and showed that a very strong OHO hydrogen bond is
      formed with proton tautomerism (PhOH...(-)OAc and PhO(-)...HOAc forms, both
      strongly hydrogen bonded). Computationally, we have employed ab initio molecular
      dynamics (70 and 71 solvent molecules, with and without the presence of a counter
      cation, respectively). We demonstrate that the relative motion of the counter
      cation and the "free" carbonyl group of the acid plays the major role in the OHO
      bond geometry and causes proton "jumps", i.e. interconversion of PhOH...(-)OAc
      and PhO(-)...HOAc tautomers. Weak H-bonds between CH(CD) groups of the solvent
      and the oxygen atom of carbonyl stabilize the PhOH...(-)OAc type of structures.
      Breaking of CH...O bonds shifts the equilibrium towards PhO(-)...HOAc form.

PMID- 25586484
TI  - Effects of resveratrol on the treatment of inflammatory response induced by
      severe burn.
AB  - The aim of this study was to preliminarily investigate the effects of resveratrol
      on the treatment of systemic inflammatory response induced by severe burn
      wounding. Through the simulation experiment in vivo on burned mice and simulative
      experiment in vitro on mice macrophage respectively, differences of the related
      pro-inflammatory cytokines and SIRT1 expression levels between the resveratrol
      treated group and the untreated control group were detected and analyzed. The
      results of the simulation experiment in vivo on burned mice manifested that the
      survival rate of the mice in the resveratrol-treated group was markedly higher
      than that of controls (p<0.05). Resveratrol could significantly reduce the levels
      of pro-inflammatory factors TNF-alpha, IL-1beta, and IL-6 in serum (p<0.01) and
      greatly elevate the expression level of SIRT1 (p<0.01). The results of the
      simulative experiment in vitro on mice macrophage showed no significant
      difference in TNF-alpha, IL-1beta, or IL-6 contents among three groups (C, mice
      macrophage control group; R, resveratrol-treated macrophage group; I, SIRT1
      inhibitor-treated macrophage group). Whereas, after lipopolysaccharide (LPS)
      activation (L group), macrophage TNF-alpha, IL-1beta, and IL-6 levels were
      significantly increased in L group, dramatically higher than those in L+R group
      (LPS and resveratrol treatment group) (p<0.01). After adding SITR1 inhibitor,
      three pro-inflammatory cytokines in L+R+I group all showed significant increases
      compared with those in L+R group (p<0.01). LPS activated macrophages were able to
      promote the expression of pro-inflammatory cytokines. By upregulating the
      expression levels of SIRT1, resveratrol could effectively inhibit the
      inflammation cascade reaction and increase the survival rate of severe burn with
      bacterial infections in a large extent.

PMID- 25586485
TI  - Blockade of Notch Signalling by gamma-Secretase Inhibitor in Lung T Cells of
      Asthmatic Mice Affects T Cell Differentiation and Pulmonary Inflammation.
AB  - Notch is a single-pass transmembrane receptor protein expressed by T cells, which
      contributes to the pathogenesis of asthma through regulation of the development
      and differentiation of T cells. gamma-Secretase inhibitor (GSI) acts as an
      effective blocker of Notch signalling. The present study aimed to investigate the
      role of GSI MW167 in T cell differentiation and antigen-induced airway
      inflammation. An OVA-induced airway inflammation mouse model was established.
      Blockade of Notch signalling was achieved using MW167. The expression of IL-4, IL
      5, IFN-gamma, Notch1 signalling and pro-inflammatory transcription factors in
      activated lung T cells was evaluated. Finally, the therapeutic effect of MW167
      was investigated by haematoxylin and eosin staining, real-time PCR and ELISA. The
      expression of IL-4 and IL-5 decreased and that of IFN-gamma increased
      significantly, and the protein expression levels of pro-inflammatory
      transcription factors reduced in active lung T cells after administration of
      MW167, compared to the control group. MW167 treatment prevented OVA-induced
      airway inflammation and histological changes. The serum and bronchoalveolar
      lavage fluid (BALF) levels of IL-4 and IL-5 in MW167-treated mice decreased
      significantly, whereas those of IFN-gamma increased, relative to the levels in
      OVA-challenged animals treated with PBS. Our findings indicate that Notch
      signalling plays an important role in the pathogenesis of asthma and that MW167
      may be a potential therapeutic target for allergen-induced airway inflammation. 

PMID- 25586488
TI  - Elucidating genetic diversity among sour orange rootstocks: a comparative study
      of the efficiency of RAPD and SSR markers.
AB  - In order to compare the effectiveness of two molecular marker systems, a set of
      six RAPD and nine SSR markers were used to study the genetic diversity in a
      population of 46 sour orange accessions, a common rootstock used in almost all
      citrus orchards in Tunisia. Genetic diversity parameters [average and effective
      number of alleles, percentage of polymorphism, polymorphic information content
      (PIC), effective marker index (EMI), and marker index (MI) parameters] for RAPD,
      SSR, and RAPD + SSR were determined in order to assess the efficiency of the two
      marker systems. The results revealed that these parameters were significantly
      higher when using RAPD markers. Similarly, cluster analysis using the results of
      RAPD was practically the same as that obtained when combining data from the two
      marker systems (RAPD + SSR) demonstrating the efficiency of RAPD in
      discriminating between sour orange accessions. Therefore, the use of SSR markers,
      known to be more efficient and discriminatory, does not bring significant
      supplementary information in this work. Indeed, results would have been obtained
      using only the RAPD markers. Accordingly, this work highlights the efficiency and
      advantages of RAPD, as an easy and efficient technique, in studying citrus
      rootstock's genetic diversity, and establishing genetic relationships among
      citrus accessions. 

PMID- 25586487
TI  - High cell density cultivation of recombinant Escherichia coli strains expressing
      2-O-sulfotransferase and C5-epimerase for the production of bioengineered
      heparin.
AB  - Bioengineered heparin is being investigated as a potential substitute for the
      animal-sourced anticoagulant drug. One step in the current process to prepare
      bioengineered heparin involves the conversion of N-sulfo heparosan, rich in ->
      4)GlcNS(1 -> 4) GlcA(1 -> sequences (where S is sulfo, GlcN is alpha-D
      glucosamine, and GlcA is beta-D-glucuronic acid), to a critical intermediate,
      rich in -> 4)GlcNS(1 -> 4) IdoA2S(1 -> sequences (where S is sulfo and IdoA is
      alpha-L-iduronic acid), using 2-O-sulfotransferase (2-OST) and C5 epimerase (C5
      epi). Until now, these heparan sulfate biosynthetic enzymes have been expressed
      in Escherichia coli grown in shake flask culture as fusion proteins. The current
      study is focused on the high cell density fed-batch cultivation of recombinant E.
      coli strains expressing both enzymes. We report the high productivity expression
      of active 2-OST and C5-epi enzymes of 6.0 and 2.2 mg/g dry cell weight,
      respectively. 

PMID- 25586489
TI  - Enhanced production of 2,3-butanediol from sugarcane molasses.
AB  - 2,3-Butanediol has been known as a platform green chemical, and the production
      cost is the key problem for its large-scale production in which the carbon source
      occupies a major part. Sugarcane molasses is a by-product of sugar industry and
      considered as a cheap carbon source for biorefinery. In this paper, the
      fermentation of 2,3-butanediol with sugarcane molasses was studied by reducing
      the medium ingredients and operation steps. The fermentation medium was optimized
      by response surface methodology, and 2,3-butanediol production was explored under
      the deficiency of sterilization, molasses acidification, and organic nitrogen
      source. Based on these experiments, the fermentation medium with sugarcane
      molasses as carbon source was simplified to five ingredients, and the steps of
      molasses acidification and medium sterilization were reduced; thus, the cost was
      reduced and the production of 2,3-butanediol was enhanced. Under fed-batch
      fermentation, 99.5 g/L of 2,3-butanediol and acetoin was obtained at 60 h with a
      yield of 0.39 g/g sugar. 

PMID- 25586490
TI  - Production of cell-penetrating peptides in Escherichia coli using an intein
      mediated system.
AB  - Cell-penetrating peptides are molecules with the ability to cross membranes and
      enter cells. Attention has been put on these peptides as a tool for drug delivery
      research, as they are able to serve as delivery vectors for large molecules.
      Intracellular delivery of bioactive peptides is a very promising research area
      for clinical applications, since peptides are able to simulate protein regions
      and thus modulate key intracellular protein-protein interactions. Therefore,
      evaluation of different strategies for production of these peptides is necessary.
      In this work, an intein-mediated system was used to evaluate Escherichia coli
      recombinant production of p53pAnt and PNC27 anticancer cell-penetrating peptides.
      It was demonstrated that the pTXB1 and the pTYB11 vector systems are suitable for
      production of this kind of peptides. The production process involves a low
      temperature induction process and an efficient on-column intein-mediated
      cleavage, which allowed an effective peptide recovery using a single
      chromatographic step. 

PMID- 25586492
TI  - Images in Vascular Medicine. Painful nodule of the forehead after blunt trauma:
      superficial temporal artery pseudoaneurysm.

PMID- 25586493
TI  - Comparative efficacy of long-acting   muscarinic antagonists in preventing COPD  
      exacerbations: a network meta-analysis and   meta-regression.
AB  - BACKGROUND: We hypothesized a class effect of currently available long-acting
      muscarinic antagonists (LAMAs; i.e., tiotropium as a dry powder inhaler or a soft
      mist inhaler, aclidinium bromide, and glycopyrronium) in preventing chronic
      obstructive pulmonary disease (COPD) exacerbations. The hypothesis was tested
      with a network meta-analysis. METHODS: Several databases and manufacturer's
      websites were searched for relevant clinical trials. Randomized, controlled
      trials, of at least 12 weeks duration, comparing a LAMA with placebo or another
      LAMA were included. Moderate-to-severe and severe exacerbations were chosen as
      the outcome assessment criteria. The data were pooled using network meta
      analysis. RESULTS: A total of 27 studies with 48,140 subjects were included. All
      LAMAs reduced moderate-to-severe exacerbations compared with placebo. However,
      there were no statistically significant differences in preventing moderate-to
      severe or severe exacerbations among LABAs. In a subgroup analysis restricting
      studies to those that had a minimum of 6 months of treatment, glycopyrronium was
      associated with the least-effective strategy and aclidinium was associated with
      the greatest probability of being the best therapy in preventing severe
      exacerbations. Our meta-regression analysis suggested that the prevention of COPD
      exacerbations were less effective in studies which allowed concomitant use of a
      long-acting beta agonist (LABA). CONCLUSION: All LAMAs were equally effective in
      preventing moderate-to-severe exacerbations. Aclidinium was associated with the
      lowest risk for severe exacerbations when treatment duration was 6 months or
      longer. The concomitant use of LABA may not enhance the efficacy of LAMAs in
      preventing COPD exacerbations. More studies are needed to further examine above
      findings.

PMID- 25586491
TI  - A disease module in the interactome explains disease heterogeneity, drug response
      and captures novel pathways and genes in asthma.
AB  - Recent advances in genetics have spurred rapid progress towards the systematic
      identification of genes involved in complex diseases. Still, the detailed
      understanding of the molecular and physiological mechanisms through which these
      genes affect disease phenotypes remains a major challenge. Here, we identify the
      asthma disease module, i.e. the local neighborhood of the interactome whose
      perturbation is associated with asthma, and validate it for functional and
      pathophysiological relevance, using both computational and experimental
      approaches. We find that the asthma disease module is enriched with modest GWAS P
      values against the background of random variation, and with differentially
      expressed genes from normal and asthmatic fibroblast cells treated with an asthma
      specific drug. The asthma module also contains immune response mechanisms that
      are shared with other immune-related disease modules. Further, using diverse
      omics (genomics, gene-expression, drug response) data, we identify the GAB1
      signaling pathway as an important novel modulator in asthma. The wiring diagram
      of the uncovered asthma module suggests a relatively close link between GAB1 and
      glucocorticoids (GCs), which we experimentally validate, observing an increase in
      the level of GAB1 after GC treatment in BEAS-2B bronchial epithelial cells. The
      siRNA knockdown of GAB1 in the BEAS-2B cell line resulted in a decrease in the
      NFkB level, suggesting a novel regulatory path of the pro-inflammatory factor
      NFkB by GAB1 in asthma. 

PMID- 25586494
TI  - Pseudoangiomatous stromal hyperplasia with multinucleated stromal giant cells is
      neither exceptional in gynecomastia nor characteristic of neurofibromatosis type
      1.
AB  - Six cases of gynecomastia with pseudoangiomatous stromal hyperplasia (PASH) and
      multinucleated stromal giant cells (MSGC) associated with neurofibromatosis type
      1 (NF1) have been reported, and finding MSGC within PASH in gynecomastia has been
      suggested as being a characteristic of NF1. The frequency of PASH with MSGC in
      gynecomastia and its specificity for NF1 have not, however, been systematically
      studied. A total of 337 gynecomastia specimens from 215 patients, aged from 8 to
      78 years (median, 22 years) were reevaluated for the presence of PASH with MSGC.
      Breast tissue samples of 25 patients were analyzed for the presence of an NF1
      gene mutation using next generation sequencing. Rare MSGC, usually in the
      background of PASH, were noted at least unilaterally in 27 (13 %) patients; and
      prominent MSGC, always in the background of PASH, were noted in 8 (4 %) patients.
      The NF1 gene was mutated in only 1 (an 8-year-old boy with known NF1 and
      prominent MSGC) of the 25 tested patients, including 6 patients with prominent
      MSGC and 19 patients with rare MSGC. MSGC, usually in the background of PASH, are
      not characteristic of NF1.

PMID- 25586495
TI  - Electron-beam induced nano-etching of suspended graphene.
AB  - Besides its interesting physical properties, graphene as a two-dimensional
      lattice of carbon atoms promises to realize devices with exceptional electronic
      properties, where freely suspended graphene without contact to any substrate is
      the ultimate, truly two-dimensional system. The practical realization of nano
      devices from suspended graphene, however, relies heavily on finding a structuring
      method which is minimally invasive. Here, we report on the first electron beam
      induced nano-etching of suspended graphene and demonstrate high-resolution
      etching down to ~7 nm for line-cuts into the monolayer graphene. We investigate
      the structural quality of the etched graphene layer using two-dimensional (2D)
      Raman maps and demonstrate its high electronic quality in a nano-device: A 25 nm
      wide suspended graphene nanoribbon (GNR) that shows a transport gap with a
      corresponding energy of ~60 meV. This is an important step towards fast and
      reliable patterning of suspended graphene for future ballistic transport, nano
      electronic and nano-mechanical devices.

PMID- 25586496
TI  - A whole-cell assay for specific inhibitors of translation initiation in bacteria.
AB  - The bacterial translational apparatus is an ideal target for the search of new
      antibiotics. In fact, it performs an essential process carried out by a large
      number of potential subtargets for antibiotic action. Moreover, it is
      sufficiently different in several molecular details from the apparatus of Eukarya
      and Archaea to generally ensure specificity for the bacterial domain. This
      applies in particular to translation initiation, which is the most different step
      in the process. In bacteria, the 30S ribosomal subunit directly binds to the
      translation initiation region, a site within the messenger RNA (mRNA) 5'
      untranslated region (5'-UTR). 30S binding is mediated by the interaction of both
      the 16S ribosomal RNA and the ribosomal protein S1 with specific regions of the
      mRNA 5'-UTR. An alternative, S1-independent pathway is enjoyed by leaderless
      mRNAs (i.e., transcripts devoid of a 5'-UTR). We have developed a simple
      fluorescence-based whole-cell assay in Escherichia coli to find inhibitors of the
      canonical S1-dependent translation initiation pathway. The assay has been set up
      both in a common E. coli laboratory strain and in a strain with an outer membrane
      permeability defect. Compared with other whole-cell assays for antibacterials,
      the major advantages of the screen described here are high sensitivity and
      specificity. 

PMID- 25586497
TI  - Methods for the creation of cyclic Peptide libraries for use in lead discovery.
AB  - The identification of initial hits is a crucial stage in the drug discovery
      process. Although many projects adopt high-throughput screening of small-molecule
      libraries at this stage, there is significant potential for screening libraries
      of macromolecules created using chemical biology approaches. Not only can the
      production of the library be directly interfaced with a cell-based assay, but
      these libraries also require significantly fewer resources to generate and
      maintain. In this context, cyclic peptides are increasingly viewed as ideal
      scaffolds and have proven capability against challenging targets such as protein
      protein interactions. Here we discuss a range of methods used for the creation of
      cyclic peptide libraries and detail examples of their successful implementation. 

PMID- 25586499
TI  - Distribution and innervation of putative peripheral arterial chemoreceptors in
      the red-eared slider (Trachemys scripta elegans).
AB  - Peripheral arterial chemoreceptors have been isolated to the common carotid
      artery, aorta, and pulmonary artery of turtles. However, the putative
      neurotransmitters associated with these chemoreceptors have not yet been
      described. The goal of the present study was to determine the neurochemical
      content, innervations, and distribution of putative oxygen-sensing cells in the
      central vasculature of turtles and to derive homologies with peripheral arterial
      chemoreceptors of other vertebrates. We used tract tracing together with
      immunohistochemical markers for cholinergic cells (vesicular acetylcholine
      transporter [VAChT]), tyrosine hydroxylase (TH; the rate-limiting enzyme in
      catecholamine synthesis), and serotonin (5HT) to identify putative oxygen-sensing
      cells and to determine their anatomical relation to branches of the vagus nerve
      (Xth cranial nerve). We found potential oxygen-sensing cells in all three
      chemosensory areas innervated by branches of the Xth cranial nerve. Cells
      containing either 5HT or VAChT were found in all three sites. The morphology and
      size of these cells resemble glomus cells found in amphibians, mammals,
      tortoises, and lizards. Furthermore, we found populations of cholinergic cells
      located at the base of the aorta and pulmonary artery that are likely involved in
      efferent regulation of vessel resistance. Catecholamine-containing cells were not
      found in any of the putative chemosensitive areas. The presence of 5HT- and VAChT
      immunoreactive cells in segments of the common carotid artery, aorta, and
      pulmonary artery appears to reflect a transition between cells containing the
      major neurotransmitters seen in fish (5HT) and mammals (ACh and adenosine).

PMID- 25586500
TI  - Determination of trans- and cis-urocanic acid in relation to histamine,
      putrescine, and cadaverine contents in tuna (Auxis Thazard) at different storage
      temperatures.
AB  - Scombroid fish poisoning is usually associated with consumption of fish
      containing high levels of histamine. However, reports indicate that some cases
      have responded to antihistamine therapy while ingested histamine levels in these
      cases were low. Potentiation of histamine toxicity by some biogenic amines, and
      release of endogenous histamine by other compounds such as cis-urocanic acid
      (UCA) are some hypotheses that have been put forth to explain this anomaly. Very
      little is known about the effects of storage conditions on the production of both
      UCA isomers and biogenic amines in tuna. Thus, the production of trans- and cis
      UCA, histamine, putrescine, and cadaverine in tuna during 15 d of storage at 0,
      3, and 10  degrees C and 2 d storage at ambient temperature were monitored. The
      initial trans- and cis-UCA contents in fresh tuna were 2.90 and 1.47 mg/kg,
      respectively, whereas the levels of putrescine and cadaverine were less than 2
      mg/kg, and histamine was not detected. The highest levels of trans- and cis-UCA
      were obtained during 15 d storage at 3  degrees C (23.74 and 21.79 mg/kg,
      respectively) while the highest concentrations of histamine (2796 mg/kg),
      putrescine (220.32 mg/kg) and cadaverine (1045.20 mg/kg) were obtained during
      storage at room temperature, 10 and 10  degrees C, respectively. Histamine
      content increased considerably during storage at 10  degrees C whereas trans- and
      cis-UCA contents changed slightly. The initial trans-UCA content decreased during
      storage at ambient temperature. Thus, unlike histamine, concentrations of trans-
      and cis-UCA did not result in elevated levels during storage of tuna. 

PMID- 25586498
TI  - Activity of quinolone CP-115,955 against bacterial and human type II
      topoisomerases is mediated by different interactions.
AB  - CP-115,955 is a quinolone with a 4-hydroxyphenyl at C7 that displays high
      activity against both bacterial and human type II topoisomerases. To determine
      the basis for quinolone cross-reactivity between bacterial and human enzymes, the
      activity of CP-115,955 and a series of related quinolones and quinazolinediones
      against Bacillus anthracis topoisomerase IV and human topoisomerase IIalpha was
      analyzed. Results indicate that the activity of CP-115,955 against the bacterial
      and human enzymes is mediated by different interactions. On the basis of the
      decreased activity of quinazolinediones against wild-type and resistant mutant
      topoisomerase IV and the low activity of quinolones against resistant mutant
      enzymes, it appears that the primary interaction of CP-115,955 with the bacterial
      system is mediated through the C3/C4 keto acid and the water-metal ion bridge. In
      contrast, the drug interacts with the human enzyme primarily through the C7 4
      hydroxyphenyl ring and has no requirement for a substituent at C8 in order to
      attain high activity. Despite the fact that the human type II enzyme is unable to
      utilize the water-metal ion bridge, quinolones in the CP-115,955 series display
      higher activity against topoisomerase IIalpha in vitro and in cultured human
      cells than the corresponding quinazolinediones. Thus, quinolones may be a viable
      platform for the development of novel drugs with anticancer potential. 

PMID- 25586502
TI  - Community-based arts initiatives: exploring the science of the arts.
AB  - In this introduction to the special issue, we describe some of the rewards and
      challenges of community-based arts initiatives for our discipline. We explore the
      inherent tensions between art and science that are reflected in community-based
      arts activities. We pose larger questions about researching community-based arts
      activities and defining the arts as a means of promoting social change. The
      diversity of populations, settings, and issues represented by the papers in the
      special issue are described and a common set of values, methods of inquiry and
      action are discussed. 

PMID- 25586501
TI  - Sleepiness, inflammation and oxidative stress markers in middle-aged males with
      obstructive sleep apnea without metabolic syndrome: a cross-sectional study.
AB  - BACKGROUND: The simultaneous occurrence of metabolic syndrome and excessive
      daytime sleepiness are very common in obstructive sleep apnea (OSA) patients.
      Both conditions, if present in OSA, have been reported to be associated with
      inflammation and disruption of oxidative stress balance that impair the
      cardiovascular system. To verify the impact of daytime sleepiness on inflammatory
      and oxidative stress markers, we evaluated OSA patients without significant
      metabolic disturbance. METHODS: Thirty-five male subjects without diagnostic
      criteria for metabolic syndrome (Adult Treatment Panel III) were distributed into
      a control group (n = 10) (43 +/- 10.56 years, apnea-hypopnea index - AHI 2.71 +/-
      1.48/hour), a non-sleepy OSA group (n = 11) (42.36 +/- 9.48 years, AHI 29.48 +/-
      22.83/hour) and a sleepy OSA group (n = 14) (45.43 +/- 10.06 years, AHI 38.20 +/-
      25.54/hour). Excessive daytime sleepiness was considered when Epworth sleepiness
      scale score was >= 10. Levels of high-sensitivity C-reactive protein,
      homocysteine and cysteine, and paraoxonase-1 activity and arylesterase activity
      of paraoxonase-1 were evaluated. RESULTS: Patients with OSA and excessive daytime
      sleepiness presented increased high-sensitivity C-reactive protein levels even
      after controlling for confounders. No significant differences were found among
      the groups in paraoxonase-1 activity nor arylesterase activity of paraoxonase-1.
      AHI was independently associated and excessive daytime sleepiness tended to have
      an association with high-sensitivity C-reactive protein. CONCLUSIONS: In the
      absence of metabolic syndrome, increased inflammatory response was associated
      with AHI and daytime sleepiness, while OSA was not associated with abnormalities
      in oxidative stress markers.

PMID- 25586503
TI  - Use and evaluation of a semi-permeable mesh implant in vertebral augmentation for
      the treatment of painful osteoporotic vertebral compression fractures.
AB  - OBJECTIVE: To assess the efficacy of a semi-permeable mesh implant in the
      treatment of painful thoracic and lumbar osteoporotic vertebral compression
      fractures. METHODS: Patients with painful thoracic and lumbar osteoporotic
      vertebral compression fractures which were refractory to conventional medical
      management and less than 3 months of age were considered possible candidates for
      this vertebral augmentation technique. Data recorded for the procedure included
      patient age, gender, fracture level and morphology, mesh implant size, amount of
      cement injected, cement extravasation, complications, and pre- and post-procedure
      numeric pain scores and Oswestry Disability Index (ODI) scores. RESULTS: 17
      patients were included in this retrospective study; 12 women and 5 men, with an
      average age of 78.6 years. Each patient had one level treated with the mesh
      implant; 4 thoracic levels and 13 lumbar levels. The 10*15 mm implant was used in
      13 treated vertebrae, including the two thoracic vertebrae; the 10*20 mm implant
      was used to treat 3 lumbar vertebrae, and one 10*25 mm implant was used to treat
      an L1 vertebra. An average of 2.4 mL of acrylic bone cement was injected, and
      there was fluoroscopic evidence of a small amount of cement leakage in one case.
      No patient related complications were seen and there were no device failures. All
      patients, followed-up to at least 3 weeks, showed significant pain relief. The
      average pretreatment numeric pain score of 9 and ODI of 50 decreased to an
      average post-treatment score of 0.6 and 12, respectively (p<0.001). CONCLUSIONS:
      Vertebral augmentation with a semi-permeable mesh stent implant can be used to
      effectively and safely treat osteoporotic vertebral compression fractures within
      the lower thoracic and lumbar spine.

PMID- 25586504
TI  - [Surgical treatment of the Charcot foot : long-term results and systematic
      review].
AB  - BACKGROUND: Because of extensive bone loss and the associated complex instability
      and deformity of the feet, Charcot arthropathy or neuroosteoarthropathy is a
      challenge for the orthopedic surgeon. Ulcerations offer entry of various
      bacteria; thus, infections are a frequent serious issue and complication. The
      careful choice of treatment is not only very important for the correct alignment
      of the foot and the loading capacity, but also contributes significantly to the
      prevention of skin irritation or the healing of existing ulcers. Above all,
      chronic plantar ulcerations, caused by prominent exostoses or axial malalignments
      are almost untreatable without surgery. Because diagnosis requires an individual
      approach, no strict regimen of therapy has become established. OBJECTIVES: The
      major objective was to reduce the number of ulcerations and infections, and to
      minimize the risk of amputation. In addition, complications and comorbidities
      were determined. Tibio-calcaneal arthrodesis is a very frequently used surgical
      treatment option. Therefore, a special focus in the following article is on this
      method. MATERIALS AND METHODS: In a 12-year period (1999-2011), 43 patients (46
      feet) suffering from Charcot foot were treated surgically. The following were
      used: triple, talo-navicular, subtalar, tibio-calcaneal arthrodesis and midfoot
      fusion bolts. The arthrodesis related to the hindfoot and tarsus and most
      commonly the tibio-calcaneal arthrodesis was applied. The reduction of load on
      the affected foot preoperatively and postoperatively by white-cast, Aircast
      walker shoe or other orthesis is essential in the treatment. For a long-term
      satisfactory outcome, an orthopedic custom-made shoe is indispensable after
      surgical treatment. RESULTS: After surgical treatment of 16 feet with
      ulcerations, 14 could be healed and only 2 suffered from complications, such as
      infections, nonunions, talus necrosis, and wound healing disorder. Revision was
      frequently necessary, although the majority of complications could be treated. In
      this population, three amputations could not be prevented. CONCLUSION: Even with
      strict aseptic techniques and years of experience in Charcot arthropathy,
      complications can occur, which can even lead to amputation. The early detection
      of the Charcot foot is the most important factor and helps to reduce morbidity
      and further complications. Co-morbid diseases (e.g., diabetes mellitus) need
      special care and optimal treatment, because they are often responsible for the
      poor surgical outcome. Finally, the ulceration rate and related complications,
      such as amputation, can be reduced by timely surgical treatment. Unfortunately,
      the progressive course of the disease often requires follow-up operations.

PMID- 25586505
TI  - [Extreme lateral interbody fusion. Indication, surgical technique, outcomes and
      specific complications].
AB  - BACKGROUND: Extreme lateral interbody fusion (XLIF) is an interbody fusion
      technique, in which access to the lateral part of the disc is achieved via a
      strong lateral transpsoatic approach. In general, the technique can be applied
      between T5 and L5. For lumbar segments, neuromonitoring is mandatory to protect
      the iliolumbar plexus during the psoas passage. OBJECTIVES: In this article, the
      results regarding use of the XLIF technique are summarized and compared with
      other anterior and anterolateral approaches. In addition, current publications
      regarding indication, technique, complications and clinical/radiological outcome
      measures are discussed. METHODS: The results of a literature review are presented
      and discussed. RESULTS: Regarding the indication and the surgical options for
      segmental restoration, the XLIF technique is comparable to anterior or
      anterolateral and open lateral interbody fusion. The minimally invasive XLIF
      access promises potentially lower morbidity than open procedures and the risk of
      injury of the iliac vessels is lower than in anterior and anterolateral
      approaches. CONCLUSION: Increasing numbers of spine surgeons are using the XLIF
      method. Current results indicate that XLIF is a safe and reproducible technique
      for deformities, adjacent level disease, and instability.

PMID- 25586507
TI  - Prognostic value of sST2 added to BNP in acute heart failure with preserved or
      reduced ejection fraction.
AB  - BACKGROUND: Natriuretic peptides and suppression of tumorigenicity 2 (ST2)
      represent two different physiopathological pathways. We evaluated the prognostic
      accuracy and complementarity of B-type natriuretic peptide (BNP) and soluble ST2
      (sST2) plasma levels at discharge from a hospital admission for acute heart
      failure, both in patients with preserved (HFpEF) and depressed (HFrEF) systolic
      function. METHODS AND RESULTS: We enrolled 195 consecutive patients discharged
      alive and followed them prospectively for 6 months. The endpoint was all-cause
      death or hospital readmission for heart failure. Seventy-six patients had HFpEF
      and 119 had HFrEF, of whom 23 (30.3%) and 43 (36.1%) reached the combined
      endpoint, respectively. In both HFpEF and HFrEF, having the two biomarkers into
      account added prognostic information, with the highest risk in patients with both
      biomarkers above the median in their group (approximately 40% hospitalization
      free survival in both groups at 6 months). These associations translated into a
      significant fourfold increase in risk of the endpoint for one elevated biomarker
      and sevenfold for both biomarkers elevated in HFrEF, and no association for one
      elevated biomarker and fivefold increase in risk for both biomarkers elevated in
      HFpEF. Considering the reclassification of risk added to BNP by measurement of
      sST2, net reclassification index was 0.31 (p = 0.21) among patients with HFpEF
      and 0.70 (p < 0.001) among patients with HFrEF. CONCLUSIONS: sST2 provides robust
      prognostic information in acute heart failure with HFrEF, while this pattern was
      less clear in HFpEF. When sST2 was measured together with BNP, it improved
      prognostic accuracy in both groups, more clearly in HFrEF.

PMID- 25586508
TI  - Ampelopsis japonica ethanol extract suppresses migration and invasion in human
      MDA-MB-231 breast cancer cells.
AB  - Ampelopsis japonica (AJ) is a well-known traditional oriental herb with anti
      inflammatory and anticancer activities. However, the molecular mechanisms by
      which AJ inhibits metastasis in breast cancer cells remain to be elucidated. The
      aim of the present study was to investigate the effects of AJ ethanol extract
      (EAJ) on highly metastatic human MDA-MB-231 breast cancer cells in vitro. AJ was
      extracted and chemically characterized. Cell proliferation was determined using a
      CCK-8 assay and migration was detected using a wound healing motility assay. A
      Transwell assay was used to evaluate the invasion and metastatic capabilities of
      the MDA-MB-231 cells. In addition, the mRNA expression levels of
      metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitors of metalloproteinases
      (TIMP)-1 and TIMP-2 were evaluated using reverse transcription quantitative
      polymerase chain reaction in vitro. The results of the present study
      characterized the signaling cascades that mediated the antimetastatic activity of
      AJ in the human MDA-MB-231 breast cancer cell line. EAJ significantly suppressed
      the migration and invasion of MDA-MB-231 cells in vitro and inhibited the
      expression of metalloproteinase (MMP)-2 and MMP-9. These findings identified the
      biological activity of EAJ in an in vitro model of cancer metastasis and provided
      a rationale for further investigation.

PMID- 25586506
TI  - Macrophage recruitment in obese adipose tissue.
AB  - Obesity is characterized as a chronic state of low-grade inflammation with
      progressive immune cell infiltration into adipose tissues. Adipose tissue
      macrophages play critical roles in the establishment of the chronic inflammatory
      state and metabolic dysfunctions. The novel discovery that pro-inflammatory
      macrophages are recruited to obese adipose tissue prompted an increased interest
      in the interplay between immune cells and metabolism. Since this discovery, many
      works have been published investigating the factors that lead to macrophage
      recruitment, the phenotypic change of adipose tissue macrophages, and metabolic
      dysfunctions. Adipokines and chemokines are key mediators that play crucial roles
      in crosstalk between adipocytes and macrophages and in regulating the adipose
      tissue inflammation. In the present review, we discuss the obesity-mediated
      adipose tissue remodelling, and particularly, the role of adipokines/chemokines
      in macrophage recruitment to obese adipose tissue. This review provides new
      insights into the physiological role of these factors and identifies a potential
      therapeutic target for obesity and associated disorders. 

PMID- 25586510
TI  - Isolation and characterization of onion degrading bacteria from onion waste
      produced in South Buenos Aires province, Argentina.
AB  - Onion production in Argentina generates a significant amount of waste. Finding an
      effective method to recycle it is a matter of environmental concern. Among
      organic waste reuse techniques, anaerobic digestion could be a valuable
      alternative to current practices. Substrate inoculation with appropriate
      bacterial strains enhances the rate-limiting step (hydrolysis) of anaerobic
      digestion of biomass wastes. Selection of indigenous bacteria with the ability to
      degrade onion waste could be a good approach to find a suitable bioaugmentation
      or pretreatment agent. We isolated bacterial strains from onion waste in
      different degradation stages and from different localities. In order to
      characterize and select the best candidates, we analyzed the growth patterns of
      the isolates in a medium prepared with onion juice as the main source of
      nutrients and we evaluated carbon source utilization. Nine strains were selected
      to test their ability to grow using onion tissue and the five most remarkable
      ones were identified by 16S rRNA gene sequencing. Strains belonged to the genera
      Pseudoxanthomonas, Bacillus, Micrococcus and Pseudomonas. Two strains, Bacillus
      subtilis subsp. subtillis MB2-62 and Pseudomonas poae VE-74 have characteristics
      that make them promising candidates for bioaugmentation or pretreatment purposes.

PMID- 25586512
TI  - Mathematical modeling improves EC50 estimations from classical dose-response
      curves.
AB  - The beta-adrenergic response is impaired in failing hearts. When studying beta
      adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is
      an important measure of ligand response. We previously measured the in vitro
      contraction force response of chicken heart tissue to increasing concentrations
      of adrenaline, and observed a decreasing response at high concentrations. The
      classical interpretation of such data is to assume a maximal response before the
      decrease, and to fit a sigmoid curve to the remaining data to determine EC50 .
      Instead, we have applied a mathematical modeling approach to interpret the full
      dose-response curve in a new way. The developed model predicts a non-steady-state
      caused by a short resting time between increased concentrations of agonist, which
      affect the dose-response characterization. Therefore, an improved estimate of
      EC50 may be calculated using steady-state simulations of the model. The model
      based estimation of EC50 is further refined using additional time-resolved data
      to decrease the uncertainty of the prediction. The resulting model-based EC50
      (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm).
      Mathematical modeling thus makes it possible to re-interpret previously obtained
      datasets, and to make accurate estimates of EC50 even when steady-state
      measurements are not experimentally feasible. DATABASE: The mathematical models
      described here have been submitted to the JWS Online Cellular Systems Modelling
      Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman.

PMID- 25586509
TI  - A European epidemiological survey of Vibrio splendidus clade shows unexplored
      diversity and massive exchange of virulence factors.
AB  - The Vibrio splendidus clade has previously been associated with epidemic
      outbreaks of various aquatic animals, as in the case of the cupped oyster,
      Crassostrea gigas. To investigate whether involved strains could present a clonal
      origin and to identify possible alternative background carriage animals or
      zooplankton, a large epidemiological survey was conducted on isolates of the
      splendidus clade. For this purpose, Vibrio strains were isolated from various
      samples including oysters, mussels, sediments, zooplankton, and sea water on the
      basis of a North/South gradient of the European sea water zone (Ireland, The
      Netherlands, France, Italy, and Spain). A total of 435 isolates were successfully
      associated to the V. splendidus clade using real time polymerase chain reaction
      with 16S specific primers and probes. A multiple-locus variable-number tandem
      repeat analysis (VNTR) was conducted on all isolates based on a multiplex PCR
      VNTR with a set of primer pairs designed from the V. tasmaniensis LGP32 genome.
      Preliminary validation of the primers on a set of collection strains from the V.
      splendidus clade confirmed that the former V. splendidus-related LGP32 and
      relative strains were related to V. tasmaniensis rather than to the type strain
      V. splendidus LMG 4042. The VNTR analysis was then successfully conducted on 335
      isolates which led to the characterization of 87 different profiles. Our results
      showed that (1) the high diversity of VNTR did not enlighten significant
      correlation between a specific pattern and the origin of collected samples.
      However, populations isolated from animal samples tend to differ from those of
      the background environment; (2) oyster mortality events could not be linked to
      the clonal proliferation of a particular VNTR type. However, few different
      patterns seemed successively associated with samples collected during peaks of
      oyster's mortality. (3) Finally, no correlation could be seen between specific
      VNTR patterns and sequence phylogeny of the virulence factors vsm and ompU that
      were detected among strains isolated during as well as outside mortality events.
      These results, combined with incongruence observed between the ompU and vsm
      phylogenetic trees, suggested both large diffusion of strains and massive lateral
      gene transfer within the V. splendidus clade.

PMID- 25586513
TI  - More challenges for machine-learning protein interactions.
AB  - MOTIVATION: Machine learning may be the most popular computational tool in
      molecular biology. Providing sustained performance estimates is challenging. The
      standard cross-validation protocols usually fail in biology. Park and Marcotte
      found that even refined protocols fail for protein-protein interactions (PPIs).
      RESULTS: Here, we sketch additional problems for the prediction of PPIs from
      sequence alone. First, it not only matters whether proteins A or B of a target
      interaction A-B are similar to proteins of training interactions (positives), but
      also whether A or B are similar to proteins of non-interactions (negatives).
      Second, training on multiple interaction partners per protein did not improve
      performance for new proteins (not used to train). In contrary, a strictly non
      redundant training that ignored good data slightly improved the prediction of
      difficult cases. Third, which prediction method appears to be best crucially
      depends on the sequence similarity between the test and the training set, how
      many true interactions should be found and the expected ratio of negatives to
      positives. The correct assessment of performance is the most complicated task in
      the development of prediction methods. Our analyses suggest that PPIs square the
      challenge for this task.

PMID- 25586511
TI  - Using saccades to diagnose covert hepatic encephalopathy.
AB  - Covert Hepatic Encephalopathy (CHE), previously known as Minimal Hepatic
      Encephalopathy, is a subtle cognitive defect found in 30-70 % of cirrhosis
      patients. It has been linked to poor quality of life, impaired fitness to drive,
      and increased mortality: treatment is possible. Despite its clinical
      significance, diagnosis relies on psychometric tests that have proved unsuitable
      for use in a clinical setting. We investigated whether measurement of saccadic
      latency distributions might be a viable alternative. We collected data on 35
      cirrhosis patients at Addenbrooke's Hospital, Cambridge, with no evidence of
      clinically overt encephalopathy, and 36 age-matched healthy controls. Performance
      on standard psychometric tests was evaluated to determine those patients with CHE
      as defined by the World Congress of Gastroenterology. We then compared visually
      evoked saccades between those with CHE and those without, as well as reviewing
      blood test results and correlating saccadic latencies with biochemical parameters
      and prognostic scores. Cirrhosis patients have significantly longer median
      saccadic latencies than healthy controls. Those with CHE had significantly
      prolonged saccadic latencies when compared with those without CHE. Analysis of a
      cirrhosis patient's saccades can diagnose CHE with a sensitivity of 75 % and a
      specificity of 75 %. We concluded that analysis of a cirrhosis patient's saccadic
      latency distributions is a fast and objective measure that can be used as a
      diagnostic tool for CHE. This improved early diagnosis could direct avoidance of
      high-risk activities such as driving, and better inform treatment strategies. 

PMID- 25586514
TI  - NLR-parser: rapid annotation of plant NLR complements.
AB  - MOTIVATION: The repetitive nature of plant disease resistance genes encoding for
      nucleotide-binding leucine-rich repeat (NLR) proteins hampers their prediction
      with standard gene annotation software. Motif alignment and search tool (MAST)
      has previously been reported as a tool to support annotation of NLR-encoding
      genes. However, the decision if a motif combination represents an NLR protein was
      entirely manual. RESULTS: The NLR-parser pipeline is designed to use the MAST
      output from six-frame translated amino acid sequences and filters for predefined
      biologically curated motif compositions. Input reads can be derived from, for
      example, raw long-read sequencing data or contigs and scaffolds coming from plant
      genome projects. The output is a tab-separated file with information on start and
      frame of the first NLR specific motif, whether the identified sequence is a TNL
      or CNL, potentially full or fragmented. In addition, the output of the NB-ARC
      domain sequence can directly be used for phylogenetic analyses. In comparison to
      other prediction software, the highly complex NB-ARC domain is described in
      detail using several individual motifs.

PMID- 25586515
TI  - QTLMiner: QTL database curation by mining tables in literature.
AB  - MOTIVATION: Figures and tables in biomedical literature record vast amounts of
      important experiment results. In scientific papers, for example, quantitative
      trait locus (QTL) information is usually presented in tables. However, most of
      the popular text-mining methods focus on extracting knowledge from unstructured
      free text. As far as we know, there are no published works on mining tables in
      biomedical literature. In this article, we propose a method to extract QTL
      information from tables and plain text found in literature. Heterogeneous and
      complex tables were converted into a structured database, combined with
      information extracted from plain text. Our method could greatly reduce labor
      burdens involved with database curation. RESULTS: We applied our method on a
      soybean QTL database curation, from which 2278 records were extracted from 228
      papers with a precision rate of 96.9% and a recall rate of 83.3%, F value for the
      method is 89.6%.

PMID- 25586516
TI  - Visits to primary care physicians among persons who inject drugs at high risk of
      hepatitis C virus infection: room for improvement.
AB  - The role of primary care physicians (PCP) in hepatitis C virus (HCV) prevention
      is increasingly emphasized. Yet, little is known about the patterns of contacts
      with PCP among persons who inject drugs (PWID). We sought to assess the 6-month
      prevalence of PCP visiting among PWID at risk of HCV infection and to explore the
      associated factors. Baseline data were collected from HCV-seronegative PWID
      recruited in HEPCO, an observational Hepatitis Cohort study (2004-2011) in
      Montreal, Canada. An interviewer-administered questionnaire elicited information
      on socio-demographic factors, drug use patterns and healthcare services
      utilization. Blood samples were tested for HCV antibodies. Using the Gelberg
      Andersen Behavioral Model, hierarchical logistic regression analyses were
      conducted to identify predisposing, need and enabling factors associated with PCP
      visiting. Of the 349 participants (mean age = 34; 80.8% male), 32.1% reported
      visiting a PCP. In the multivariate model, among predisposing factors, male
      gender [adjusted odds ratio (AOR) = 0.45 (0.25-0.83)], chronic homelessness [AOR
      = 0.08 (0.01-0.67)], cocaine injection [AOR = 0.46 (0.28-0.76)] and reporting
      greater illegal or semi-legal income [AOR = 0.48 (0.27-0.85)] were negatively
      associated with PCP visits. Markers of need were not associated with the outcome.
      Among enabling factors, contact with street nurses [AOR = 3.86 (1.49-9.90)] and
      food banks [AOR = 2.01 (1.20-3.37)] was positively associated with PCP visiting.
      Only one third of participating PWID reported a recent visit to a PCP. While a
      host of predisposing factors seems to hamper timely contacts with PCP among high
      risk PWID, community-based support services may play an important role in
      initiating dialogue with primary healthcare services in this population.

PMID- 25586518
TI  - In tandem or alone: a remarkably selective transfer hydrogenation of alkenes
      catalyzed by ruthenium olefin metathesis catalysts.
AB  - A system for transfer hydrogenation of alkenes, composed of a ruthenium
      metathesis catalyst and HCOOH, is presented. This operationally simple system can
      be formed directly after a metathesis reaction to effect hydrogenation of the
      metathesis product in a single-pot. These hydrogenation conditions are applicable
      to a wide range of alkenes and offer remarkable selectivity. 

PMID- 25586517
TI  - High-Dose Robotic Stereotactic Body Radiotherapy in the Treatment of Patients
      With Prostate Cancer: Preliminary Results in 26 Patients.
AB  - BACKGROUND: Stereotactic body radiotherapy (SBRT) can emulate high dose rate
      brachytherapy (HDR-BRT) dose fractionation. We report our preliminary results
      using SBRT in monotherapy or pre-external-beam radiotherapy (EBRT) boost in
      patients with localized prostate cancer (LpC). The primary end point was the
      evaluation of both acute and late toxicities; secondary end point was the
      observation of prostate-specific antigen (PSA) nadir. PATIENTS AND METHODS:
      Patients with LpC having prostate volume <=90 cm(3) were enrolled in the present
      study. Patients were treated with SBRT alone or in combined modality (SBRT +
      EBRT). SBRT was performed using a CyberKnife System (Accuray Incorporated,
      Sunnyvale, California) and fiducial tracking system. RESULTS: From February 2008
      to July 2013, 21 patients for monotherapy (38 Gy/4 fractions) and 5 for combined
      modality (9.5 Gy/2 fractions plus 46 Gy/23 fractions EBRT) were enrolled.
      Androgen deprivation therapy (ADT) was administered in 16 of the 26 patients. The
      median pretreatment PSA was 9.4 (range, 4.5-14.3) ng/mL. All patients completed
      the planned therapy. Acute Grade 1 toxicity was observed in 18 patients,
      genitourinary (GU) in 12 / 26 patients, and gastrointestinal (GI) in 6 / 26
      patients. Acute Grade 2 GU toxicity was reported in 1 / 26 patients, and Grade 2
      GI toxicity was observed in 2 / 26 patients. The median PSA nadir was 0.15
      (range, 0.02 = 1.4) ng/mL. Late toxicities were observed in 5 / 26 patients:
      Grade 1 GU (3 of 26), Grade 2 GU (1 of 26), and Grade 1 GI (1 of 26). Median
      follow-up was 21.5 (range, 8-65) months. CONCLUSIONS: Our preliminary results of
      SBRT "simulating" HDR for LpC confirm a minimal toxicity and an optimal PSA
      response. The PSA nadirs appear comparable with HDR-BRT.

PMID- 25586519
TI  - Versatile colorant syntheses by multiple condensations of acetyl anilines with
      perylene anhydrides.
AB  - We report a key step forward in rylene chemistry: the transformation of rylenes
      into novel chromophore families. The imidization of rylene anhydrides with 2
      acetyl anilines could be controlled by the choice of the solvent, thus causing a
      transformation into either a 4-hydroxyquinoline (4-HQ) or a 4-oxoquinoline (4-OQ)
      unit. The 4-OQ motif contains an aminoenone group formed by intramolecular aldol
      condensation and is the first vinylogous rylene imide. The concept of vinylogy
      was further developed by utilizing 2,6-diacetyl aniline leading to an 3a-aza-1,6
      phenalenedione-extended rylene skeleton fully embracing the nitrogen atom. By
      functionalization of the aminoenone motifs, for example, malononitrile addition
      at the carbonyl groups, the optical and electronic properties could be further
      tuned. 

PMID- 25586520
TI  - Statin treatment for older adults: the impact of the 2013 ACC/AHA cholesterol
      guidelines.
AB  - The 2013 American College of Cardiology (ACC) and American Heart Association
      (AHA) practice guidelines for the treatment of blood cholesterol significantly
      changed the paradigm of how providers should prescribe statin therapy, especially
      for older adults. While the evidence supports statin therapy for older adults
      with cardiovascular disease for secondary prevention and with high cardiovascular
      risk for primary prevention, the evidence is lacking for older adults without
      major cardiovascular risk aside from age. The unclear evidence base for older
      adults must be considered along with the potential harms of statin therapy when
      incorporating the 2013 ACC/AHA practice guidelines for considering statin
      treatment, particularly for primary prevention for older adults. 

PMID- 25586521
TI  - Whole genome sequencing: a new paradigm in the surveillance and control of human
      tuberculosis.
AB  - Whole Genome Sequencing (WGS) is emerging as a very powerful tool for the
      management, outbreak analyses, surveillance and determining drug resistance of
      human infectious pathogens including Mycobacterium tuberculosis and MRSA. WGS can
      also discriminate relapse TB from re-infection and the resolution provided by WGS
      has no comparison to conventional technologies. With current cost coming down to
      <L70 per bacterial genome, WGS has emerged as an alternative to all the existing
      technologies put together. We discuss the advantage and disadvantages of WGS and
      whether it can become a point of care tool in not just developed countries but
      also in developing countries which have a huge TB burden. The likely utility of
      WGS for other pathogens and also in characterizing holobionts is also discussed. 

PMID- 25586522
TI  - Attitudes towards subsequent entry biologics/biosimilars: A survey of Canadian
      rheumatologists.
AB  - Globally, patents on several well established biologic agents used to treat
      rheumatic diseases have already or will expire over the next few years, allowing
      for the availability of subsequent entry biologics (SEBs or biosimilars). The
      objective of this study was to identify gaps in knowledge and attitudes towards
      SEBs among Canadian rheumatologists. Eighty-one rheumatologists completed the
      survey and were included in the analysis (22 % of the 369 who were contacted). We
      found that one third of physicians (31 %) were familiar with SEBs and that
      physicians with greater than 20 years of practice were significantly more likely
      to be familiar or very familiar with SEBs compared to respondents with less than
      10 years or 10-20 years of experience (OR 11.1, 95 % CI: 2.1-55.5, p = 0.004 and
      OR 4.5, 95 % CI: 1.2-16.2, p = 0.023, respectively). A third (32 %) of physicians
      agreed or strongly agreed that they would be comfortable with indication
      extrapolation. Most respondents (88 %) would feel concerned or very concerned if
      a pharmacist had the ability to substitute a biologic drug for an SEB without the
      physician's approval. This survey was the first study that evaluated the position
      of rheumatologists on key areas surrounding SEBs from a nationwide Canadian
      perspective. Current physician attitudes and perceptions of SEBs can inform
      future educational initiatives and highlight important issues for payers, policy
      makers, and other stakeholders.

PMID- 25586523
TI  - Importance of serum amyloid-A in Behcet's disease.

PMID- 25586525
TI  - Luteolin acts as a radiosensitizer in non-small cell lung cancer cells by
      enhancing apoptotic cell death through activation of a p38/ROS/caspase cascade.
AB  - To improve radiation therapy, the development of effective radiosensitizer is
      required. Fifty percent inhibitory concentration (IC50) values of 3',4',5',7'
      tetrahydroxyflavone (luteolin) against NCI-H460 and -H1299 non-small cell lung
      cancer (NSCLC) cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assays. Radiosensitizing activity was assessed
      in vitro by treating cells with luteolin prior to irradiation of gamma-ionizing
      radiation (IR), and performing cell count and clonogenic assays. Cell signaling
      pathways involved in the radiosensitizing effects of luteolin were examined using
      propidium iodide (PI) uptake, reactive oxygen species (ROS) detection and
      immunoblot assays, with or without specific chemical inhibitors. Apoptotic cell
      death was confirmed by PI uptake and immunoblot assays. In vivo radiosensitizing
      activity was tested using an NCI-H460 cell xenograft model in nude mice. Tumor
      size was measured and apoptosis was determined with terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) assay in animals in four treatment
      groups: mock-treated control, luteolin only, IR only, and luteolin plus IR.
      Treatment with luteolin or IR induced NSCLC cell death in vitro, but the
      combination of luteolin pre-treatment and IR was more effective than either agent
      alone, yielding dose enhancement ratios (DERs) of 1.22 and 1.35 for NCI-H460 and 
      H1299 cells, respectively. Combined treatment with luteolin and IR enhanced
      apoptotic cell death in association with downregulation of B-cell lymphoma 2 (Bcl
      2) and activation of caspase-3, -8, and -9; it also induced phosphorylation of
      p38 mitogen-activated protein kinase (MAPK) and ROS accumulation. Inhibition of
      p38 MAPK decreased ROS production, and inhibition of either p38 MAPK or ROS
      production attenuated apoptotic cell death and activation of caspase-8 and -9. In
      a xenograft model, tumor growth was delayed by 21.8 days in the luteolin/IR
      combination group compared with controls, and apoptotic cell death was increased.
      The enhancement factor of the luteolin and IR combination was 1.83. Collectively,
      these findings indicate that luteolin acts as a radiosensitizer by enhancing
      apoptotic cell death through activation of a p38/ROS/caspase cascade.

PMID- 25586524
TI  - Effects of different dosage of dexamethasone on behavioral, electrophysiological,
      and histomorphological recovery in a chronic sciatic nerve compression model.
AB  - OBJECTIVE: To investigate the effects of different doses of topical dexamethasone
      (Dex) on sciatic nerves with simulated compressive neuropathy. METHODS: Thirty
      two Wistar rats were divided into four groups of 8: Sham group: no compression of
      the sciatic nerve + no treatment; Saline: chronic compression of the left sciatic
      nerve for 4 weeks + saline; 0.8% Dex: chronic compression + 0.8 mg of Dex; 3.2%
      Dex: chronic compression + 3.2 mg of Dex. Two sponge strips soaked with saline or
      Dex were placed under and over the nerve for 30 min in both Dex groups. Mixed
      nerve-elicited somatosensory evoked potentials (M-SSEPs) and compound muscle
      action potentials (CMAPs) were measured to verify the compressive neuropathy in
      post-treatment follow-up. Behavioral observations of thermal hyperalgesia tests
      were quantified before electrophysiological examinations. Treated and
      contralateral nerves were harvested for histomorphological analysis. RESULTS: M
      SSEP and CMAP amplitudes significantly decreased and latencies were significantly
      prolonged on postcompression thermal hyperalgesia tests. Rats in both Dex groups
      showed significant improvement in both sensory and motor conductive values and in
      neurological function, as well as increased mean myelin diameter on the final
      histomorphological examination. For rats in the saline group, these parameters
      showed incomplete recovery compared with the Sham group and the precompression
      baseline. Moreover, the changes after Dex treatment were not dose-dependent.
      CONCLUSIONS: Topical Dex reversed electrophysiological, behavioral, and
      structural changes in chronically compressed sciatic nerves. Differences between
      the beneficial effects of high-dose and low-dose Dex were nonsignificant.

PMID- 25586528
TI  - Obesity and androgens: Masculinity or muscularity?

PMID- 25586526
TI  - Challenging patient deaths in pediatric oncology.
AB  - PURPOSE: Pediatric oncologists look after patients and their families for
      extended periods of time when they are diagnosed and treated for cancer. Twenty
      percent of these children will die while under their care. The purpose of this
      study was to explore what makes patient deaths challenging for pediatric
      oncologists. METHODS: Twenty-one Canadian pediatric oncologists were interviewed
      about their experiences with patient death and were probed about the factors that
      make patient deaths particularly challenging. Data were analyzed using the
      grounded theory method. RESULTS: Challenging factors pertaining to patient death
      were categorized into three main domains. Relational factors included dealing
      with families perceived as challenging; identifying with parents; and having long
      term relationships and special connections with patients and their caregivers.
      The second domain captured the process of death and dying and included death
      after curative treatment was stopped; death caused by complications; and
      unexpected deaths. The third domain encompassed patient factors that included
      suffering of the child, and the sense that no child should die. CONCLUSIONS: The
      types of relationships pediatric oncologists have with patients and caregivers,
      and the process by which children die affects pediatric oncologists' perceived
      level of difficulty in coping with the death. The findings point to the
      complexity of working with children where parents are included in the decision
      making processes around a child's treatment. Implementation of structured review
      opportunities around patient death and associated decision-making within a
      multidisciplinary healthcare team may alleviate some of the emotional burden
      associated with patient deaths.

PMID- 25586527
TI  - Validation and real-world assessment of the Functional Assessment of Anorexia
      Cachexia Therapy (FAACT) scale in patients with advanced non-small cell lung
      cancer and the cancer anorexia-cachexia syndrome (CACS).
AB  - PURPOSE: Patients with cancer anorexia-cachexia syndrome (CACS) suffer a
      significant symptom burden, impaired quality of life (QoL), and shorter survival.
      Measurement of QoL impairments related to CACS is thereby important both in
      clinical practice and in research. We aimed to further validate the Functional
      Assessment of Anorexia-Cachexia Therapy (FAACT) scale in an advanced lung cancer
      population. METHODS: We tested the performance of the FAACT and its anorexia
      cachexia subscale (ACS) within a dataset of patients with advanced non-small cell
      lung cancer (aNSCLC), using standard statistical methods. We then compared the
      performance of commonly used QoL measures stratified by CACS status and by
      patient self-report of appetite and weight loss. RESULTS: The FAACT and its ACS
      demonstrate internal validity consistent with acceptable published ranges for
      other QoL scales (Cronbach alpha = 0.9 and 0.79, respectively). Correlation
      coefficients demonstrate moderate correlations in the expected directions between
      FAACT and ACS and scales that measure related constructs. Comparing patients with
      and without CACS, the ACS is more sensitive to change than other QoL instruments
      (mean score 33.1 vs. 37.2, p = 0.011, ES = 0.58). CONCLUSION: In patients with
      aNSCLC, the FAACT and its ACS performed well compared with other instruments,
      further supporting their validity and value in clinical research. FAACT and ACS
      scores covaried with symptoms and other QoL changes that are typical hallmarks of
      CACS, lending further support to their use as QoL endpoints in clinical trials
      among patients with CACS.

PMID- 25586529
TI  - A correlation between the weight of visceral adipose tissue and selected
      anthropometric indices: an autopsy study.
AB  - WHAT IS ALREADY KNOWN ON THE SUBJECT: Several anthropometric indices are used as
      an estimation of the true amount of body fat, e.g. the body mass index (BMI).
      These indices correlate well with each other and with non-invasive measurements
      of total body fat and visceral adipose tissue. The indices generally show a
      strong correlation with cardiovascular disease and diabetes mellitus. WHAT THIS
      STUDY ADDS: Direct measurement of visceral adipose tissue by weight (VAW) from
      autopsy cases positively correlates with the anthropometric indices. VAW also
      positively correlates with fatty tissue thickness at separate locations, i.e.
      renal capsular and epicardial fatty tissue. VAW is positively correlated with the
      severity of cardiosclerosis and diabetes mellitus, but there is no significant
      difference in VAW between deaths from cardiovascular complications and other
      natural deaths. SUMMARY: Different anthropometric indices and non-invasive
      methods have been used to estimate the total burden of body fat. Increased
      visceral adipose tissue is believed to involve elevated risk for cardiovascular
      disease, type 2 diabetes, chronic kidney disease and hypertension. At present,
      the optimal method to estimate the visceral and total amount of fat remains
      undecided. In the present study of 201 autopsy cases, direct measurement of
      visceral adipose tissue by weight (VAW) has been compared to common
      anthropometric indices, namely body mass index (BMI), waist-to-hip ratio (W/Hip
      ratio), waist-to-height ratio (W/Height ratio), body adiposity index (BAI), waist
      circumference and abdominal wall thickness. The prevalence and severity of
      cardiovascular disease, diabetes mellitus and cause of death were also correlated
      with the anthropometric data. The outcome was that all anthropometric
      measurements showed a significant positive correlation with the weight of
      visceral adipose tissue, and the r-value of the comparison to waist circumference
      was the highest (r = 0.82). Thickness of fatty tissue enveloping the kidneys and
      heart, as well as heart weight, was also strongly correlated with VAW. VAW was
      significantly higher in men compared with women, and in diabetes mellitus
      compared with non-diabetic patients. VAW was also positively correlated with the
      severity of coronary artery sclerosis. On the contrary, there was no significant
      difference between high and low VAW comparing between deaths from cardiovascular
      complications and natural deaths from other causes. The conclusion is that the
      anthropometric measurements give a good approximation of the real amount of
      visceral fat, and that waist circumference and W/Height ratio show the best
      correlations.

PMID- 25586530
TI  - Efficacy and safety of long-term low-calorie diet in severely obese patients non
      eligible for surgery.
AB  - The aim of this study was to describe the long-term efficacy and safety of low
      calorie diets (LCDs; providing 900 kcal day(-1) ) in obese patients who have
      failed to achieve adequate weight loss with standard medical management and are
      non-eligible for surgical therapeutic options. Charts from a regional hospital
      based outpatient bariatric programme were reviewed. Eight patients (75% male, age
      60.1 +/- 7.8 years) with severe obesity (body mass index 57.1 +/- 8.8 kg m(-2) )
      and undergoing long-term LCD (33 +/- 10 months) were identified. Variables of
      interest included anthropometric, cardiovascular risk and nutritional parameters,
      thyroid, renal and liver function, changes in medications, side effects and
      adverse events. Average weight loss was 44 +/- 15 kg (27 +/- 13% of initial
      weight) at 24 months. Long-term management with LCD resulted in substantial and
      sustained improvements in glucose homeostasis, blood pressure and lipid profile.
      LCD was well tolerated with minor self-limited side effects. Over the follow-up
      period, two subjects underwent coronary revascularization and one patient
      underwent knee replacement surgery - all recovered without complications. These
      findings suggest that in selected obese patients (non-eligible for surgery), long
      term management with LCD may provide an alternative option for substantial and
      sustainable weight loss with significant improvements in metabolic and
      cardiovascular health. 

PMID- 25586531
TI  - Roux-en-Y gastric bypass patients hospitalized for substance use disorders
      achieve successful weight loss despite poor psychosocial outcomes.
AB  - An emerging body of literature indicates that Roux-en-Y gastric bypass (RYGB)
      patients may be at a heightened risk for substance use disorders (SUDs) after
      surgery. Little is known about how weight loss and psychosocial outcomes of RYGB
      patients who develop SUD differ from those who do not. The present study compared
      weight loss and psychosocial outcomes of 26 post-RYGB patients in inpatient SUD
      treatment with those of 26 RYGB patients who did not evidence problematic
      substance use in the post-operative period. SUD and control cases were matched on
      age, sex and time lapse since surgery. No significant differences in % total
      weight loss or % excess weight loss (EWL) were found between groups. Those in SUD
      treatment were significantly less likely to meet the surgical failure criteria of
      <50% EWL but evidenced greater symptoms of depression, higher rates of probable
      major depressive disorder and poorer quality of life. Our findings indicate that
      RYGB patients hospitalized for SUDs achieve successful weight loss despite having
      poor psychosocial outcomes. 

PMID- 25586533
TI  - Type 2 diabetes in children.

PMID- 25586532
TI  - Assessment of overweight and obesity among Nigerian children and adolescents
      using triceps skin-fold thickness and body mass index.
AB  - The prevalence of obesity is increasing in children and adolescents even in
      resource-poor countries. The study aimed to determine the prevalence of obesity
      in a group of Nigerian school children using triceps skin-fold thickness (SFT)
      and body mass index (BMI). The subjects were 1235 randomly selected primary and
      secondary Lagos school children aged 5-18 years, triceps SFT was measured with
      Harpenden(r) calipers and BMI calculated from weight and height. Using BMI,
      overweight and obesity were defined as values of 85th to 94th percentile for age
      and sex and >=95th percentile, respectively. Using triceps SFT, obesity was
      defined as SFT > 85th percentile of the NHANES III study. Fifty-seven subjects
      (15 boys and 42 girls) had SFT > 85th percentile with a higher prevalence in
      girls than boys (6.4% vs. 2.6%, P = 0.001). The prevalence of BMI-defined
      overweight and obesity were also higher among girls (11.9% vs. 5.7%, P < 0.001
      and 4.7% vs. 2.2%, P = 0.02, respectively). Females of upper socioeconomic class
      were more likely to be overweight (16.2% vs. 6.6%, P < 0.0001), obese (6.3% vs.
      2.8%, P = 0.03) or have elevated SFT (8.2% vs. 4.2%, P = 0.03) than those of low
      socioeconomic status. Forty-seven of 57 subjects (82.5%) with elevated SFT also
      had high BMI. The prevalence of obesity is low in the study population but the
      much higher prevalence of overweight suggests that steps should be taken to
      control fatness before the figures worsen. In more than 80% of subjects, elevated
      SFT co-existed with elevated BMI. 

PMID- 25586534
TI  - Accumulation of amyloid in cognitive impairment after mild traumatic brain
      injury.
AB  - Recent epidemiology studies have indicated that traumatic brain injury (TBI) can
      increase the risk of developing neurodegenerative diseases such as Alzheimer's
      disease (AD). Amyloid-beta (Abeta) plaques and neurofibrillary tangles are
      pathological indicators of AD. The accumulation of Abeta is considered the first
      step of AD pathophysiology. Compelling studies have supported the hypothesis that
      TBI accelerates the formation and accumulation of Abeta. These findings could
      link TBI with AD, although the research that reported these findings had
      limitations, particularly regarding mild TBI (mTBI) patients. The effects of mTBI
      on Abeta accumulation remain uncertain because of a lack of mTBI pathology data.
      Using amyloid-positron emission tomography (amyloid-PET), researchers can help to
      determine whether mTBI increases the accumulation of Abeta, which might be
      involved in the pathophysiological mechanisms of mTBI in AD, and could be a
      target for the treatment of neurodegenerative diseases associated with TBI. In
      this study, we recruited 27 mTBI patients with mTBI in mean 6years before this
      study (21 mTBI patients without cognitive impairment, 6 mTBI patients with
      cognitive impairment,) and 10 controls. All of them underwent mini-mental state
      examination, apolipoprotein E (APOE) genotyping, and amyloid-PET. The results
      show an increase of amyloid accumulation and allele frequency of APOE4 in the
      mTBI patients with cognitive impairment. These findings indicate that amyloid
      accumulation is an important indicator of cognitive impairment, and amyloid-PET
      should be a safe and useful tool for diagnosing amyloid-related cognitive
      impairment. APOE allele might play a role in the occurrence of cognitive
      impairment after mTBI. The contribution of mTBI to the amyloid accumulation
      requires further study, and mTBI patients should be recruited for longitudinal
      research with repeated amyloid-PET studies. 

PMID- 25586535
TI  - Wallerian degeneration of the bilateral middle cerebellar peduncles.

PMID- 25586536
TI  - Immunological differences between classical phenothypes of multiple sclerosis.
AB  - Multiple sclerosis (MS), one of the most serious inflammatory and
      neurodegenerative conditions, is characterized by variable clinical courses -
      relapsing-remitting (RRMS), primary progressive (PPMS) and secondary progressive
      (SPMS). Although PPMS affects only 10-15% of the patient population, its course
      and pathophysiological and immunological background are distinct. In this review
      we present and discuss main differences between different types of MS, with
      particular focus on the underlying immunological mechanisms. 

PMID- 25586537
TI  - Mitochondrial recessive ataxia syndrome: A neurological rarity not to be missed.

PMID- 25586539
TI  - Unusual cerebral white matter change in a Chinese family with Spinocerebellar
      ataxia type 12.
AB  - In a Chinese family with Spinocerebellar ataxia type 12 (SCA12), presenting with
      action tremor, mild cerebellar dysfunction, and hyperreflexia, genetic testing
      revealed abnormal CAG repeat length in the brain-specific protein phosphatase 2,
      regulatory subunit B, beta isoform (PPP2R2B) gene. To our knowledge, this is the
      first report on patients with SCA12 presenting with prominent cerebral white
      matter change besides cerebral and/or cerebellar atrophy. 

PMID- 25586540
TI  - Autotriggering caused by cardiogenic oscillation during pressure support
      ventilation.

PMID- 25586541
TI  - Mock circulation loop to investigate hemolysis in a pulsatile total artificial
      heart.
AB  - Hemocompatibility of blood pumps is a crucial parameter that has to be ensured
      prior to in vivo testing. In contrast to rotary blood pumps, a standard for
      testing a pulsatile total artificial heart (TAH) has not yet been established.
      Therefore, a new mock circulation loop was designed to investigate hemolysis in
      the left ventricle of the ReinHeart TAH. Its main features are a high
      hemocompatibility, physiological conditions, a low priming volume, and the
      conduction of blood through a closed tubing system. The mock circulation loop
      consists of a noninvasive pressure chamber, an aortic compliance chamber, and an
      atrium directly connected to the ventricle. As a control pump, the clinically
      approved Medos-HIA ventricular assist device (VAD) was used. The pumps were
      operated at 120 beats per minute with an aortic pressure of 120 to 80 mm Hg and a
      mean atrial pressure of 10 mm Hg, generating an output flow of about 5 L/min.
      Heparinized porcine blood was used. A series of six identical tests were
      performed. A test method was established that is comparable to ASTM F 1841, which
      is standard practice for the assessment of hemolysis in continuous-flow blood
      pumps. The average normalized index of hemolysis (NIH) values of the VAD and the
      ReinHeart TAH were 0.018 g/100 L and 0.03 g/100 L, respectively. The standard
      deviation of the NIH was 0.0033 for the VAD and 0.0034 for the TAH. Furthermore,
      a single test with a BPX-80 Bio-Pump was performed to verify that the hemolysis
      induced by the mock circulation loop was negligible. The performed tests showed a
      good reproducibility and statistical significance. The mock circulation loop and
      test protocol developed in this study are valid methods to investigate the
      hemolysis induced by a pulsatile blood pump. 

PMID- 25586538
TI  - Candidate pathway-based genetic association study of platinum and platinum-taxane
      related toxicity in a cohort of primary lung cancer patients.
AB  - BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common
      toxicity secondary to chemotherapy. Genetic factors may be important in
      predisposing patients to this adverse effect. PATIENTS AND METHODS: We studied
      950 primary lung cancer patients, who received platinum or platinum-combination
      drug chemotherapy and who had DNA available for study. We analyzed
      epidemiological risk factors in 279 CIPN patients and 456 non-CIPN patients and
      genetic risk factors in 141 CIPN patients and 259 non-CIPN patients. The risk
      factors studied included demographic, diagnostic, and treatment data, as well as
      174 tag SNPs (single nucleotide polymorphisms) across 43 candidate genes in the
      glutathione, cell cycle, DNA repair, cell signaling, and apoptosis pathways.
      RESULTS: Patients who had diabetes mellitus were more likely to have CIPN
      (p=0.0002). Other epidemiologic risk factors associated with CIPN included number
      of cycles (p=0.0004) and type of concurrent chemotherapy (p<0.001). SNPs most
      associated with CIPN were in glutathione peroxidase 7 (GPX7) gene (p values
      0.0015 and 0.0028, unadjusted and adjusted) and in ATP-binding cassette sub
      family C member 4 (ABCC4) gene (p values 0.037 and 0.006, unadjusted and
      adjusted). We also found other suggestive associations in methyl-o-guanine-methyl
      transferase (MGMT) and glutathione-S-transferase (GST) isoforms. CONCLUSIONS:
      Epidemiological and genetic risk factors associated with CIPN in this cohort,
      included the type of chemotherapy drug, intensity of chemotherapy treatment, and
      genes known to be associated with chemotherapy resistance. These findings suggest
      that differentiating between cytotoxic and neurotoxic mechanisms of chemotherapy
      drugs is challenging but represents an important step toward individualized
      therapy and improving quality of life for patients.

PMID- 25586542
TI  - Serotonergic, brain volume and attentional correlates of trait anxiety in
      primates.
AB  - Trait anxiety is a risk factor for the development and maintenance of affective
      disorders, and insights into the underlying brain mechanisms are vital for
      improving treatment and prevention strategies. Translational studies in non-human
      primates, where targeted neurochemical and genetic manipulations can be made, are
      critical in view of their close neuroanatomical similarity to humans in brain
      regions implicated in trait anxiety. Thus, we characterised the serotonergic and
      regional brain volume correlates of trait-like anxiety in the marmoset monkey.
      Low- and high-anxious animals were identified by behavioral responses to a human
      intruder (HI) that are known to be sensitive to anxiolytic drug treatment.
      Extracellular serotonin levels within the amygdala were measured with in vivo
      microdialysis, at baseline and in response to challenge with the selective
      serotonin reuptake inhibitor, citalopram. Regional brain volume was assessed by
      structural magnetic resonance imaging. Anxious individuals showed persistent,
      long-term fearful responses to both a HI and a model snake, alongside sustained
      attention (vigilance) to novel cues in a context associated with unpredictable
      threat. Neurally, high-anxious marmosets showed reduced amygdala serotonin
      levels, and smaller volumes in a closely connected prefrontal region, the dorsal
      anterior cingulate cortex. These findings highlight behavioral and neural
      similarities between trait-like anxiety in marmosets and humans, and set the
      stage for further investigation of the processes contributing to vulnerability
      and resilience to affective disorders. 

PMID- 25586544
TI  - The long-term consequences of preterm birth: what do teachers know?
AB  - AIM: The knowledge and information needs of education professionals were assessed
      to determine how prepared they feel to support the growing number of preterm
      children entering schools today. METHOD: In a national survey, 585 teachers and
      212 educational psychologists completed the Preterm Birth-Knowledge Scale (PB-KS)
      to assess knowledge of outcomes following preterm birth. Total scores (range 0
      33) were compared between groups and the impact of demographic characteristics on
      knowledge was analysed. Training and information needs were also assessed.
      RESULTS: Teaching staff (mean 14.7, SD 5.5) had significantly lower knowledge
      scores than educational psychologists (mean 17.1, SD 5.0; p<0.001); both had
      significantly lower scores than neonatal clinicians surveyed previously (mean
      26.0, SD 3.6; p<0.001). Education professionals' poorest areas of knowledge
      related to the most frequent adverse outcomes following preterm birth. Only 16%
      of teaching staff had received training about preterm birth and more than 90%
      requested more information. Having a special educational needs role and being
      employed at least 16 years were associated with higher knowledge scores.
      INTERPRETATION: Education professionals have poor knowledge of the needs of
      children born preterm and most feel ill-equipped to support them in school. As
      teachers have primary responsibility for providing long-term support for children
      born preterm, this is of significant public health and educational concern.

PMID- 25586546
TI  - Identification of nanoscale ingredients in commercial food products and their
      induction of mitochondrially mediated cytotoxic effects on human mesenchymal stem
      cells.
AB  - Titanium dioxide (E171) and silicon dioxide (E551) are common additives found in
      food products, personal-care products, and many other consumer products used in
      daily life. Recent studies have reported that these food additives (manufactured
      E171 and E551) contain nanosized particles of less than 100 nm. However, the
      particle size distribution and morphology of added TiO2 and SiO2 particles are
      not typically stated on the package label. Furthermore, there is an increasing
      debate regarding health and safety concerns related to the use of synthetic food
      additives containing nanosized ingredients in consumer products. In this study,
      we identified the size and morphology of TiO2 and SiO2 particles in commercially
      available food products by using transmission electron microscope (TEM). In
      addition, the in vitro toxicological effects of E171 and E551 on human
      mesenchymal stem cells (hMSCs), an adult stem cell-based model, were assessed
      using the MTT assay and a flow cytometry-based JC-1 assay. Our TEM results
      confirmed the presence of nanoscale ingredients in food products, and the in
      vitro toxicology results indicated that the nanoscale E171 and E551 ingredients
      induced dose-dependent cytotoxicity, changes in cellular morphology, and the loss
      of mitochondrial trans-membrane potential in hMSCs. These preliminary results
      clearly demonstrated that the nanoscale E171 and E551 particles had adverse
      effects on hMSCs by inducing oxidative stress-mediated cell death. Accordingly,
      further studies are needed to identify the specific pathway involved, with an
      emphasis on differential gene expression in hMSCs. 

PMID- 25586545
TI  - Effect of orexin A on apoptosis in BGC-823 gastric cancer cells via OX1R through
      the AKT signaling pathway.
AB  - Orexins are a class of peptides involved in the regulation of food intake, energy
      homeostasis, the sleep-wake cycle and gastrointestinal function. Recent studies
      have demonstrated that orexin A may influence apoptosis and proliferation in
      numerous types of cancer cells. However, the effect of orexin A on gastric cancer
      cells and its mechanisms of action remain elusive. In the present study, BGC-823
      gastric cancer cells were treated with orexin A (10-10-10-6 M) in vitro and the
      expression levels of orexin receptor 1 (OX1R) protein in cells was then
      determined. The proliferation, viability and apoptosis of BGC-823 cells were
      detected. In addition, BGC-823 cells were treated with AKT inhibitor PF-04691502
      or OX1R-specific antagonist SB334867 in combination with orexin A, in order to
      examine the activation of AKT and caspase-3. The results showed that orexin A (10
      10-10-6 M) stimulated the OX1R protein expression in BGC-823 cells, which
      improved the proliferation and viability of the cells as well as protected them
      from apoptosis. Phosphorylated AKT protein was significantly increased in BGC-823
      cells following treatment with orexin A. Moreover, 10-8 M orexin A reduced the
      proapoptotic activity of caspase-3 (by <=30%). The OX1R antagonist SB334867 (10-6
      M) and AKT antagonist PF-04691502 (10-6 M), when used individually or in
      combination, abolished the effect of orexin A (10-8 M) on BGC-823 cells. In
      conclusion, the results of the present study demonstrated that orexin A inhibited
      gastric cancer cell apoptosis via OX1R through the AKT signaling pathway.

PMID- 25586543
TI  - The EPA2 adhesin encoding gene is responsive to oxidative stress in the
      opportunistic fungal pathogen Candida glabrata.
AB  - Candida glabrata has emerged as an important opportunistic pathogen in both
      mucosal and bloodstream infections. C. glabrata contains 67 adhesin-like
      glycosylphosphatidylinositol-cell-wall proteins (GPI-CWPs), which are classified
      into seven groups and the largest is the Epa family. Epa proteins are very
      diverse and their expression is differentially regulated. Like many of the EPA
      genes, EPA2 is localized in a subtelomeric region where it is subject to
      chromatin-based transcriptional silencing and its role remains largely
      unexplored. In this study, we show that EPA2 gene is induced specifically in
      vitro in the presence of oxidative stress generated by H2O2. This induction is
      dependent on both Yap1 and Skn7, whereas Msn4 represses EPA2 expression.
      Interestingly, EPA2 is not induced during phagocytosis, but its expression can be
      identified in the liver in a murine model of systemic infection. Epa2 has no
      effect on the virulence of C. glabrata. The work presented herein provides a
      foundation for future studies to dissect the molecular mechanism(s) by which EPA2
      of C. glabrata can be induced in the presence of oxidative stress in a region
      subject to subtelomeric silencing. 

PMID- 25586547
TI  - A systematic review and economic evaluation of intraoperative tests [RD-100i one
      step nucleic acid amplification (OSNA) system and Metasin test] for detecting
      sentinel lymph node metastases in breast cancer.
AB  - BACKGROUND: In breast cancer patients, sentinel lymph node biopsy is carried out
      at the same time as the removal of the primary tumour to postoperatively test
      with histopathology for regional metastases in the sentinel lymph node. Those
      patients with positive test results are then operated on 2-4 weeks after primary
      surgery to remove the lymph nodes from the axilla (axillary lymph node
      dissection, ALND). New molecular tests RD-100i [one-step nucleic acid
      amplification (OSNA); based on messenger RNA amplification to identify the
      cytokeratin-19 (CK19) gene marker] (Sysmex, Norderstedt, Germany) and Metasin
      (using the CK19 and mammaglobin gene markers) (Cellular Pathology, Princess
      Alexandra Hospital NHS Trust, Harlow, UK) are intended to provide an
      intraoperative diagnosis, thereby avoiding the need for postoperative
      histopathology and, in positive cases, a second operation for ALND. OBJECTIVE: To
      evaluate the clinical effectiveness and cost-effectiveness of using OSNA and
      Metasin in the NHS in England for the intraoperative diagnosis of sentinel lymph
      nodes metastases, compared with postoperative histopathology, the current
      standard. DATA SOURCES: Electronic databases including MEDLINE, MEDLINE In
      Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library and the
      Health Economic Evaluations Database as well as clinical trial registries, grey
      literature and conference proceedings were searched up to July 2012. REVIEW
      METHODS: A systematic review of the evidence was carried out using standard
      methods. Single-gate studies were used to estimate the accuracy of OSNA with
      histopathology as the reference standard. The cost-effectiveness analysis adapted
      an existing simulation model of the long-term costs and health implications of
      early breast cancer diagnostic outcomes. The model accounted for the costs of an
      extended first operation with intraoperative testing, the loss of health-related
      quality of life (disutility) from waiting for postoperative test results,
      disutility and costs of a second operation, and long-term costs and disutility
      from lymphoedema related to ALND, adjuvant therapy, locoregional recurrence and
      metastatic recurrence. RESULTS: A total of 724 references were identified in the
      searches, of which 17 studies assessing test accuracy were included in the
      review, 15 on OSNA and two on Metasin. Both Metasin studies were unpublished.
      OSNA sensitivity of 84.5% [95% confidence interval (CI) 74.7% to 91.0%] and
      specificity of 91.8% (95% CI 87.8% to 94.6%) for patient nodal status were
      estimated in a meta-analysis of five studies [unadjusted for tissue allocation
      bias (TAB)]. At these values and a 20% node-positive rate, OSNA resulted in
      lifetime discounted cost-savings of L498 and a quality-adjusted life-year (QALY)
      loss of 0.048 relative to histopathology, that is, L4324 saved per QALY lost. The
      most favourable plausible scenario for OSNA in terms of the node-positive rate
      (range 10-40%), diagnostic accuracy values (91.3% sensitivity and 94.2%
      specificity, from three reports that adjusted for TAB), the costs of
      histopathology, OSNA and second surgery, and long-term costs and utilities
      resulted in a maximum saving per QALY lost of L10,500; OSNA sensitivity and
      specificity would need to be >= 95% for this figure to be >= L20,000.
      LIMITATIONS: There is limited evidence on the diagnostic test accuracy of
      intraoperative tests. The quality of information on costs of resource utilisation
      during the diagnostic pathway is low and no evidence exists on the disutility of
      waiting for a second surgery. No comparative studies exist that report clinical
      outcomes of intraoperative diagnostic tests. These knowledge gaps have more
      influence on the decision than current uncertainty in the performance of
      postoperative histopathology in standard practice. CONCLUSIONS: One-step nucleic
      acid amplification is not cost-effective for the intraoperative diagnosis of
      sentinel lymph node metastases. OSNA is less accurate than histopathology and the
      consequent loss of health benefits in this patient group is not compensated for
      by health gains elsewhere in the health system that may be obtained with the cost
      savings made. The evidence on Metasin is insufficient to evaluate its cost
      effectiveness. STUDY REGISTRATION: This study is registered as PROSPERO
      CRD42012002889. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 25586549
TI  - Comparison of mathematical models for red marrow and blood absorbed dose
      estimation in the radioiodine treatment of advanced differentiated thyroid
      carcinoma.
AB  - Metastatic and recurrent differentiated thyroid carcinoma is preferably treated
      with (131)I, whose administered activity is limited by red marrow (RM) toxicity,
      originally correlated by Benua to a blood absorbed dose higher than 2 Gy.
      Afterward a variety of dosimetric approaches has been proposed. The aim of this
      work is to compare the results of the Benua formula with the ones of other three
      blood and RM absorbed dose formulae. Materials and methods have been borrowed by
      the dosimetric protocol of the Italian Internal Dosimetry group and adapted to
      the routine of our centre. Wilcoxon t-tests and percentage differences have been
      applied for comparison purposes. Results are significantly different (p < 0.05)
      from each other, with an average percentage difference between Benua versus other
      results of -22%. The dosimetric formula applied to determine blood or RM absorbed
      dose may contribute significantly to increase heterogeneity in absorbed dose and
      dose-response results. Standardization should be a major objective.

PMID- 25586548
TI  - Concomitant analysis of Helios and Neuropilin-1 as a marker to detect thymic
      derived regulatory T cells in naive mice.
AB  - Regulatory T (Treg) cells are characterized by the expression of CD4, CD25 and
      the intracellular Foxp3. However, these markers do not indicate whether Treg
      cells are thymic derived Treg (tTreg) cells or peripherally induced Treg (pTreg)
      cells. Recently, Helios and Neuropilin-1 (Nrp1) has been reported as potential
      markers for tTreg cells. Herein, we used flow cytometry to examine the proportion
      of CD4(+)CD8(-)CD25(+) Treg cells expressing Helios, Nrp1 and Foxp3 in thymus,
      pancreatic draining lymph nodes (PDLNs) and spleen of CD-1 mice, and thymus of
      NOD and C57BL/6 mice. The frequency of Helios(+) cells was higher than that of
      Nrp1(+) cells in CD4(+)CD8(-)CD25(+) and CD4(+)CD8(-)CD25(+)Foxp3(+) Treg cells
      in thymus. Interestingly, the proportion of IL-10(+), Ebi3(+)and CTLA-4(+) cells
      was higher in Helios(+) than Nrp1(+) tTreg cells. The anti-apoptotic activity of
      Helios(+) tTreg cells was higher in thymus compared to Nrp1(+) tTreg cells. Nrp1
      seems to be expressed at a later developmental stage compared to Helios and
      Foxp3. Furthermore, the expression of Nrp1 in CD4(+)CD25(+) T cells of younger
      mice did not increase after stimulating them in vitro with anti-CD3 and -CD28.
      Thus, under these conditions, Helios could be considered a more reliable marker
      for distinguishing tTreg cells from pTreg cells than Nrp1. 

PMID- 25586550
TI  - Tethered cord syndrome associated with a thickened filum terminale in a dog.

PMID- 25586551
TI  - Newly isolated Penicillium oxalicum A592-4B secretes enzymes that degrade milled
      rice straw with high efficiency.
AB  - An enzyme producing micro-organism, which can directly saccharify rice straw that
      has only been crushed without undergoing the current acid or alkaline
      pretreatment, was found. From the homology with the ITS, 28S rDNA sequence, the
      strain named A592-4B was identified as Penicillium oxalicum. Activities of the
      A592-4B enzymes and commercial enzyme preparations were compared by Novozymes
      Cellic CTec2 and Genencore GC220. In the present experimental condition, activity
      of A592-4B enzymes was 2.6 times higher than that of CTec2 for degrading milled
      rice straw. Furthermore, even when a quarter amount of A592-4B enzyme was applied
      to the rice straw, the conversion rate was still higher than that by CTec2. By
      utilizing A592-4B enzymes, improved lignocellulose degradation yields can be
      achieved without pre-treatment of the substrates; thus, contributing to cost
      reduction as well as reducing environmental burden. 

PMID- 25586552
TI  - Benign-appearing urothelial tissue fragments in noninstrumented voided urine
      specimens are associated with low rates of urothelial neoplasia.
AB  - BACKGROUND: The presence of urothelial tissue fragments (UTF) in voided urine
      (VU) is often considered an abnormal finding that may be associated with the
      presence of urothelial papillary neoplasms. In the current study, the authors
      reviewed VU specimens containing benign-appearing UTF (BUTF) to determine the
      associated rate of urothelial neoplasia at the study institution. METHODS: A
      retrospective search of the electronic pathology database system over a 5-year
      period (2009-2013) revealed 1131 VU specimens containing UTF. Of these, 459 cases
      (40.6%) did not have a recent history of instrumentation. Fifteen cases were
      excluded because the slides were not available for review. In the remaining 444
      cases, 274 cases (61.7%) had BUTF. A total of 170 cases (38.3%) had UTF with
      atypical cytologic features and were therefore excluded. RESULTS: Of the 274
      cases, 29 (10.6%) had follow-up surgical pathology specimens available. The
      overall rate of urothelial neoplasia on follow-up was 3.6% for low-grade
      urothelial neoplasia (10 cases) and 0.7% for high-grade urothelial carcinoma (2
      cases). Forty-five cases (16.4%) were determined to have urinary tract stones on
      follow-up. CONCLUSIONS: The presence of BUTF in VU specimens requires careful
      examination of the medical history because their presence may be explained by
      recent instrumentation. If recent instrumentation is not identified, the etiology
      of BUTF is not usually determined; in the current study, BUTF were found to be
      associated with urinary tract stones in 16.4% of cases. They also present a low
      risk of low-grade urothelial neoplasia (3.6%) and high-grade urothelial carcinoma
      (0.7%) when compared with the overall benign category at the study institution
      (2.3% [P =.15] and 0.7%, respectively).

PMID- 25586553
TI  - Novel approach to systematic random sampling in population surveys: Lessons from
      the United Arab Emirates National Diabetes Study (UAEDIAB).
AB  - BACKGROUND: The prevalence of diabetes has risen rapidly in the Middle East,
      particularly in the Gulf Region. However, some prevalence estimates have not
      fully accounted for large migrant worker populations and have focused on minority
      indigenous populations. The objectives of the UAE National Diabetes and Lifestyle
      Study are to: (i) define the prevalence of, and risk factors for, T2DM; (ii)
      describe the distribution and determinants of T2DM risk factors; (iii) study
      health knowledge, attitudes, and (iv) identify gene-environment interactions; and
      (v) develop baseline data for evaluation of future intervention programs.
      METHODS: Given the high burden of diabetes in the region and the absence of
      accurate data on non-UAE nationals in the UAE, a representative sample of the non
      UAE nationals was essential. We used an innovative methodology in which non-UAE
      nationals were sampled when attending the mandatory biannual health check that is
      required for visa renewal. Such an approach could also be used in other countries
      in the region. RESULTS: Complete data were available for 2719 eligible non-UAE
      nationals (25.9% Arabs, 70.7% Asian non-Arabs, 1.1% African non-Arabs, and 2.3%
      Westerners). Most were men < 65 years of age. The response rate was 68%, and the
      non-response was greater among women than men; 26.9% earned less than UAE Dirham
      (AED) 24 000 (US$6500) and the most common areas of employment were as managers
      or professionals, in service and sales, and unskilled occupations. Most (37.4%)
      had completed high school and 4.1% had a postgraduate degree. CONCLUSION: This
      novel methodology could provide insights for epidemiological studies in the UAE
      and other Gulf States, particularly for expatriates.

PMID- 25586554
TI  - Influence of capsule shell composition on the performance indicators of
      hypromellose capsule in comparison to hard gelatin capsules.
AB  - The purpose of this study was to assess the in vitro performances of "vegetable"
      capsules in comparison to hard gelatin capsules in terms of shell weight
      variation, reaction to different humidity conditions, resistance to stress in the
      absence of moisture, powder leakage, disintegration and dissolution. Two types of
      capsules made of HPMC produced with (Capsule 2) or without (Capsule 3) a gelling
      agent and hard gelatin capsules (Capsule 1) were assessed. Shell weight
      variability was relatively low for all tested capsules shells. Although Capsule 1
      had the highest moisture content under different humidity conditions, all capsule
      types were unable to protect the encapsulated hygroscopic polyvinylpyrrolidone
      (PVP) powder from surrounding humidity. The initial disintegration for all
      Capsule 1 occurred within 3 min, but for other types of capsules within 6 min (n
      = 18). Dissolution of acetaminophen was better when the deionized water (DIW)
      temperature increased from 32 to 42  degrees C in case of Capsule 1, but the
      effect of temperature was not significant for the other types of capsules.
      Acetaminphen dissolution from Capsule 1 was the fastest (i.e. >90% in 10 min) and
      independent of the media pH or contents unlike Capsule 2 which was influenced by
      the pH and dissolution medium contents. It is feasible to use hypromellose
      capsules shells with or without gelling agent for new lines of pharmaceutical
      products, however, there is a window for capsule shells manufacturing companies
      to improve the dissolution of their hypromellose capsules to match the
      conventional gelatin capsule shells and eventually replace them. 

PMID- 25586555
TI  - A survey of patient preferences for oral antihyperglycemic therapy in patients
      with type 2 diabetes mellitus.
AB  - INTRODUCTION: Previous research has demonstrated a correlation among patient
      preferences, dosing burden, and medication nonadherence, a well-recognized
      challenge in type 2 diabetes mellitus (T2DM). The objective of this study was to
      elicit preferences for alternative dosing regimens for oral antihyperglycemic
      therapies among patients with T2DM and to quantify differences in dosing
      preferences among patients with different characteristics. METHODS: Preferences
      for dosing of oral antihyperglycemic drugs (OAD) were evaluated by surveying
      patients with T2DM in the United States (US). Survey participants were adult US
      patients with T2DM who were taking no or only 1 OAD and no injectable therapies.
      Each patient completed a web-enabled discrete-choice experiment (DCE) including a
      series of 8 pairs of hypothetical OAD profiles. Each profile was defined by
      reductions in average glucose, dosing schedule (e.g., once-weekly, once-daily, or
      twice-daily dosing), chance of mild-to-moderate gastrointestinal side effects,
      frequency of hypoglycemia, weight change, incremental risk of congestive heart
      failure, and cost. Each participant also answered a direct question about dosing
      preference. Random-parameters logit was used to analyze the DCE data.
      Prespecified subgroups were analyzed. RESULTS: Of 2,262 patients invited to
      participate, 923 were included in the analysis (mean age 63 years, 45% male, 79%
      white). Reducing dosing frequency was statistically significantly important to
      patients; however, it was relatively less important than medication cost or
      clinical outcomes. On average, patients preferred once-weekly to once-daily
      dosing. Patients not currently taking an OAD had a stronger preference for once
      weekly dosing than patients on treatment (P = 0.012). Patients younger than 45
      years had a stronger preference for weekly dosing than older patients (P <
      0.075). CONCLUSIONS: For younger patients and patients not currently on
      treatment, once-weekly dosing may provide additional incentive to initiate and
      adhere to antihyperglycemic treatment; however, additional research will be
      required to confirm this hypothesis.

PMID- 25586557
TI  - Antibody-targeted vaccination to lung dendritic cells generates tissue-resident
      memory CD8 T cells that are highly protective against influenza virus infection.
AB  - Influenza virus gains entry into the body by inhalation and initiates its
      replication cycle within the lung. The early stage of infection, while the virus
      is confined to the lung mucosa, provides the ideal window of opportunity for an
      effective immune response to control the infection. Tissue-resident memory (Trm)
      CD8 T cells, located in a variety of tissues including the lung, are ideally
      situated to act during this window and stall the infection. The factors involved
      in the differentiation of lung Trm cells remain poorly defined. We demonstrate
      that recognition of antigen presented locally by dendritic cells (DCs) and
      transforming growth factor-beta (TGFbeta) signaling are both required. We
      exploited this knowledge to develop an antibody-targeted vaccination approach to
      generate lung Trm cells. Delivering antigen exclusively to respiratory DCs
      results in the development of lung CD8 Trm cells that are highly protective
      against lethal influenza challenge. Our results describe an effective vaccination
      strategy that protects against influenza virus infection. 

PMID- 25586556
TI  - PPARgamma activation following apoptotic cell instillation promotes resolution of
      lung inflammation and fibrosis via regulation of efferocytosis and proresolving
      cytokines.
AB  - Changes in macrophage phenotype have been implicated in apoptotic cell-mediated
      immune modulation via induction of peroxisome proliferator-activated receptor
      gamma (PPARgamma). In this study, we characterized PPARgamma induction by
      apoptotic cell instillation over the course of bleomycin-induced lung injury in
      C57BL/6 mice. Next, the role of PPARgamma activation in resolving lung
      inflammation and fibrosis was investigated. Our data demonstrate that apoptotic
      cell instillation after bleomycin results in immediate and prolonged enhancement
      of PPARgamma mRNA and protein in alveolar macrophages and lung. Moreover,
      PPARgamma activity and expression of its target molecules, including CD36,
      macrophage mannose receptor, and arginase 1, were persistently enhanced following
      apoptotic cell instillation. Coadministration of the PPARgamma antagonist,
      GW9662, reversed the enhanced efferocytosis, and the reduced proinflammatory
      cytokine expression, neutrophil recruitment, myeloperoxidase activity,
      hydroxyproline contents, and fibrosis markers, including type 1 collagen alpha2,
      fibronectin and alpha-smooth muscle actin (alpha-SMA), in the lung by apoptotic
      cell instillation. In addition, inhibition of PPARgamma activity reversed the
      expression of transforming growth factor-beta (TGF-beta), interleukin (IL)-10,
      and hepatocyte growth factor (HGF). These findings indicate that one-time
      apoptotic cell instillation contributes to anti-inflammatory and antifibrotic
      responses via upregulation of PPARgamma expression and subsequent activation,
      leading to regulation of efferocytosis and production of proresolving cytokines. 

PMID- 25586558
TI  - Interleukin (IL)-21 promotes intestinal IgA response to microbiota.
AB  - Commensal microbiota-specific T helper type 17 (Th17) cells are enriched in the
      intestines, which can convert into T follicular helper (Tfh) in Peyer's patches,
      and are crucial for production of intestinal immunoglobulin A (IgA) against
      microbiota; however, the role of Th17 and Tfh cytokines in regulating the mucosal
      IgA response to enteric microbiota is still not completely known. In this study,
      we found that intestinal IgA was impaired in mice deficient in interleukin (IL)
      17 or IL-21 signaling. IL-21, but not IL-17, is able to augment B-cell
      differentiation to IgA(+) cells as mediated by transforming growth factor beta1
      (TGFbeta1) and accelerate IgA class switch recombination (CSR). IL-21 and
      retinoic acid (RA) induce IgA(+) B-cell development and IgA production and drives
      autocrine TGFbeta1 production to initiate IgA CSR. Repletion of T-cell-deficient
      TCRbetaxdelta(-/-) mice with Th17 cells specific for commensal bacterial antigen
      increased the levels of IgA(+) B cells and IgA production in the intestine, which
      was blocked by neutralizing IL-21. Thus IL-21 functions to strongly augment IgA
      production under intestinal environment. Furthermore, IL-21 promotes intestinal B
      cell homing through alpha4beta7 expression, alone or with TGFbeta and RA.
      Together, IL-21 from microbiota-specific Th17 and/or Tfh cells contributes to
      robust intestinal IgA levels by enhancing IgA(+) CSR, IgA production and B-cell
      trafficking into the intestine. 

PMID- 25586559
TI  - Dysbiotic bacteria translocate in progressive SIV infection.
AB  - Infection of gut-resident CD4(+) memory T cells during acute human
      immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection is
      associated with rapid loss of these cells and damage to the epithelial barrier.
      Damage to the epithelial barrier allows translocation of microbial products from
      the intestinal lumen into the body. Immune activation caused by these microbial
      products has been associated with disease progression. Although microbial
      translocation has been demonstrated in SIV-infected nonhuman primates, the
      identity of translocating bacteria has not been determined. In this study we
      examined the communities of bacteria both within the gastrointestinal (GI) tract
      and systemic tissues of both healthy and experimentally SIV-infected Asian
      macaques. Although there were only modest changes in the GI tract-associated
      microbiome resulting from infection, there is substantial dysbiosis after
      administration of antiretrovirals. Analysis of bacterial DNA isolated from
      tissues of infected animals revealed a preference for the phylum Proteobacteria,
      suggesting that they preferentially translocate. Consistent with this finding, we
      observed increased metabolic activity of Proteobacterial species within the
      colonic lumen of SIV-infected animals. Overall, these data provide insights into
      disease progression and suggest that therapies aimed at altering the composition
      and metabolic activity of the GI tract microbiome could benefit chronically HIV
      infected individuals, particularly those on antiretroviral therapies. 

PMID- 25586561
TI  - Three-dimensional structures of laccases.
AB  - Laccases are phenol oxidases that belong to the family of multi-copper oxidases
      and the superfamily of cupredoxins. A number of potential industrial applications
      for laccases have led to intensive structure-function studies and an increased
      amount of crystal structures has been solved. The objective of this review is to
      summarize and analyze available crystal structures of laccases. The experimental
      crystallographic data are now easily available from the websites and electron
      density maps can be used for the interpretation of the structural models. The
      crystal structures can give valuable insights into the functional mechanisms and
      may serve as the basis for the development of laccases for industrial
      applications. 

PMID- 25586560
TI  - Laccase engineering by rational and evolutionary design.
AB  - Laccases are considered as green catalysts of great biotechnological potential.
      This has attracted a great interest in designing laccases a la carte with
      enhanced stabilities or activities tailored to specific conditions for different
      fields of application. Over 20 years, numerous efforts have been taken to
      engineer these multicopper oxidases and to understand their reaction mechanisms
      by site-directed mutagenesis, and more recently, using computational calculations
      and directed evolution tools. In this work, we review the most relevant
      contributions made in the field of laccase engineering, from the comprehensive
      study of their structure-function relationships to the tailoring of outstanding
      biocatalysts.

PMID- 25586563
TI  - Inferring the microscopic surface energy of protein-protein interfaces from
      mutation data.
AB  - Mutations at protein-protein recognition sites alter binding strength by altering
      the chemical nature of the interacting surfaces. We present a simple surface
      energy model, parameterized with empirical DeltaDeltaG values, yielding mean
      energies of -48 cal mol(-1) A(-2) for interactions between hydrophobic surfaces, 
      51 to -80 cal mol(-1) A(-2) for surfaces of complementary charge, and 66-83 cal
      mol(-1) A(-2) for electrostatically repelling surfaces, relative to the aqueous
      phase. This places the mean energy of hydrophobic surface burial at -24 cal mol(
      1) A(-2) . Despite neglecting configurational entropy and intramolecular changes,
      the model correlates with empirical binding free energies of a functionally
      diverse set of rigid-body interactions (r = 0.66). When used to rerank docking
      poses, it can place near-native solutions in the top 10 for 37% of the complexes
      evaluated, and 82% in the top 100. The method shows that hydrophobic burial is
      the driving force for protein association, accounting for 50-95% of the cohesive
      energy. The model is available open-source from
      http://life.bsc.es/pid/web/surface_energy/ and via the CCharpPPI web server
      http://life.bsc.es/pid/ccharppi/.

PMID- 25586564
TI  - Estimation of heritability for varied indexes of handedness.
AB  - Inconsistent results of the molecular studies for handedness have been reported.
      One of the key issues involved could be ways of assessing handedness. The current
      study aimed to identify the index of handedness better reveal the genetic
      component, which showed higher heritability. We measured handedness using the
      Annett's handedness questionnaire. The college students participating in this
      study filled the questionnaire in the class while their first-degree relatives
      returned questionnaires one to two weeks later. A total of 1,968 subjects
      returned their questionnaires, including 640 college students and 1,328 first
      degree relatives. Among the 449 college students returning at least one
      handedness questionnaire for their parents, a total of 449 fathers, 440 mothers,
      and 425 siblings participated in the study. The index of mixed-handedness (e.g.,
      Degree of Handedness) showed highest heritability (0.67), followed by the Hand
      Preference Index (0.52), and then the Direction of Handedness (0.39). Using an
      index of mixed-handedness for future molecular studies was suggested. 

PMID- 25586567
TI  - The support for newly qualified practitioners and new staff entering the critical
      care environment.

PMID- 25586565
TI  - Evaluation of a 64Cu-labeled 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic
      acid (NODAGA)-galactose-bombesin analogue as a PET imaging probe in a gastrin
      releasing peptide receptor-expressing prostate cancer xenograft model.
AB  - Gastrin-releasing peptide receptor (GRPR) is overexpressed by a variety of human
      tumors and in particular, identified to be upregulated in prostate cancers. The
      current study aimed to develop clinically translatable BBN analogue-based
      radioligands for positron emission tomography (PET) of GRPR-positive tumors. We
      developed radiolabeled BBN analogues and modified radiolabeled galacto-BBN
      analogues and then investigated their tumor-targeting efficacy in vivo. The
      chelator 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA) was
      used to radiolabel the peptides with 64Cu. The peptides were evaluated by
      measuring cell-based receptor-binding affinities. Biodistribution experiments and
      small animal imaging using PET were performed in nude mice bearing subcutaneous
      PC3 human prostate cancer xenografts. The conjugates were radiolabeled with
      yields >99%. The stability assay showed that [64Cu]NODAGA-BBN and [64Cu]NODAGA
      galacto-BBN remained stable in both human and mouse serum for 1 h at 37C. PET
      images of PC3 tumor-bearing nude mice were acquired at 1, 3, 24, 48 and 72 h
      after injection. [64Cu]NODAGA-galacto-BBN showed retention in tumors for 72 h,
      low liver uptake, and rapid renal clearance. PET imaging results were also
      confirmed by biodistrubution 1 and 3 h after injection. [64Cu]NODAGA-BBN and
      [64Cu]NODAGA-galacto-BBN are promising new PET probes for GRPR-positive prostate
      cancer.

PMID- 25586566
TI  - A case of late presenting unicuspid aortic valve in a 62-year-old female.
AB  - We describe the case of a 62-year-old female presenting with new onset
      progressive dyspnea on exertion and a new diagnosis of aortic stenosis.
      Transesophageal echocardiography showed fusion of the aortic valve leaflets
      suspicious for bicuspid aortic valve with dilated ascending aorta. Surgical
      replacement of the valve revealed a unicuspid aortic valve with one true
      commissure at the level of the left and noncoronary cusps. The case is supported
      by clinical, echocardiographic and angiographic imaging and discussion of current
      imaging modalities used in diagnosis of aortic valve pathology. 

PMID- 25586568
TI  - 5th International BACCN Conference - delivering high quality and safe critical
      care services: a global ambition.

PMID- 25586573
TI  - Enterobius vermicularis: an unusual cause of recurrent urinary tract infestation
      in a 7-year-old girl: case report and review of the literature.
AB  - Enterobius vermicularis, the pinworm, is one of the most prevalent intestinal
      parasites in the world. Ectopic infestations in the genital or urinary tracts
      rarely occur and chronic enterobiasis of the urinary tract has rarely been
      reported. Here we present such a case in a 7-year-old girl presenting with fever,
      pain in the abdomen, vomiting and burning micturition. Ultrasonography and
      micturating cystourethrogram (MCU) studies were normal. The ova were demonstrated
      from both the patient's urine and stool specimen. This child was treated
      successfully with Albendazole and Ivermectin. 

PMID- 25586574
TI  - Acute lower limb ischemia complicating pemetrexed and carboplatin combination
      chemotherapy for malignant pleural mesothelioma.
AB  - Pemetrexed and Carboplatin are two well-known chemioterapic agents used for the
      treatment of many tumors, especially for lung cancer and mesothelioma. Peripheral
      ischemic events related to Pemetrexed and Carboplatin are rarely reported. We
      herein report a case of lower limb acute ischemia related to combined treatment
      of Pemetrexed and Carboplatin. A 68-year-old woman was given the chemiotherapic
      treatment with combination of Pemetrexed and Carboplatin after pleural resection
      for a malignant pleural mesothelioma. Immediately after the second cycle of
      treatment, the patient experienced sudden acute left lower limb ischemia.
      Symptoms resolved after an intra-operative thrombolytic and spasmolytic therapy.

PMID- 25586562
TI  - Metabolic restructuring and cell fate conversion.
AB  - Accumulating evidence implicates mitochondrial and metabolic pathways in the
      establishment of pluripotency, as well as in the control of proliferation and
      differentiation programs. From classic studies in mouse embryos to the latest
      findings in adult stem cells, human embryonic and induced pluripotent stem cells,
      an increasing number of evidence suggests that mitochondrial and metabolic
      related processes might intertwine with signaling networks and epigenetic
      rewiring, thereby modulating cell fate decisions. This review summarizes the
      progresses in this exciting field of research. Dissecting these complex
      mitochondrial and metabolic mechanisms may lead to a more comprehensive
      understanding of stemness biology and to potential improvements in stem cell
      applications for biomedicine, cell therapy, and disease modeling. 

PMID- 25586575
TI  - Alfalfa microsymbionts from different ITS and nodC lineages of Ensifer meliloti
      and Ensifer medicae symbiovar meliloti establish efficient symbiosis with alfalfa
      in Spanish acid soils.
AB  - Alfalfa (Medicago sativa L.) is an important crop worldwide whose cropping in
      acid soils is hampered by the poor nodulation and yield commonly attributed to
      the sensitivity of its endosymbionts to acid pH. In this work, we isolated
      several acid-tolerant strains from alfalfa nodules in three acid soils in
      northwestern Spain. After grouping by RAPD fingerprinting, most strains were
      identified as Ensifer meliloti and only two strains as Ensifer medicae according
      to their 16S-23S intergenic spacer (ITS) sequences that allowed the
      differentiation of two groups within each one of these species. The two ITS
      groups of E. meliloti and the ITS group I of E. medicae have been previously
      found in Medicago nodules; however, the group II of E. medicae has been only
      found to date in Prosopis alba nodules. The analysis of the nodC gene showed that
      all strains isolated in this study belong to the symbiovar meliloti, grouping
      with the type strains of E. meliloti or E. medicae, but some harboured nodC gene
      alleles different from those found to date in alfalfa nodules. The strains of E.
      medicae belong to the symbiovar meliloti which should be also recognised in this
      species, although they harboured a nodC allele phylogenetically divergent to
      those from E. meliloti strains. Microcosm experiments showed that inoculation of
      alfalfa with selected acid-tolerant strains significantly increased yields in
      acid soils representing a suitable agricultural practice for alfalfa cropping in
      these soils. 

PMID- 25586576
TI  - Zebrafish gut colonization by mCherry-labelled lactic acid bacteria.
AB  - A critical feature of probiotic microorganisms is their ability to colonize the
      intestine of the host. Although the microbial potential to adhere to the human
      gut lumen has been investigated in in vitro models, there is still much to
      discover about their in vivo behaviour. Zebrafish is a vertebrate model that is
      being widely used to investigate various biological processes shared with humans.
      In this work, we report on the use of the zebrafish model to investigate the in
      vivo colonization ability of previously characterized probiotic lactic acid
      bacteria. Lactobacillus plantarum Lp90, L. plantarum B2 and Lactobacillus
      fermentum PBCC11.5 were fluorescently tagged by transfer of the pRCR12 plasmid,
      which encodes the mCherry protein and which was constructed in this work. The
      recombinant bacteria were used to infect germ-free zebrafish larvae. After
      removal of bacteria, the colonization ability of the strains was monitored until
      3 days post-infection by using a fluorescence stereomicroscope. The results
      indicated differential adhesion capabilities among the strains. Interestingly, a
      displacement of bacteria from the medium to the posterior intestinal tract was
      observed as a function of time that suggested a transient colonization by
      probiotics. Based on fluorescence observation, L. plantarum strains exhibited a
      more robust adhesion capability. In conclusion, the use of pRCR12 plasmid for
      labelling Lactobacillus strains provides a powerful and very efficient tool to
      monitor the in vivo colonization in zebrafish larvae and to investigate the
      adhesion ability of probiotic microorganisms.

PMID- 25586577
TI  - Ammonia-oxidizing bacteria and archaea in wastewater treatment plant sludge and
      nearby coastal sediment in an industrial area in China.
AB  - Under the increasing pressure of human activities, Hangzhou Bay has become one of
      the most seriously polluted waters along China's coast. Considering the excessive
      inorganic nitrogen detected in the bay, in this study, the impact of an effluent
      from a coastal industrial park on ammonia-oxidizing microorganisms (AOMs) of the
      receiving area was interpreted for the first time by molecular technologies.
      Revealed by real-time PCR, the ratio of archaeal amoA/bacterial amoA ranged from
      5.68 * 10(-6) to 4.79 * 10(-5) in the activated sludge from two wastewater
      treatment plants (WWTPs) and 0.54-3.44 in the sediments from the effluent
      receiving coastal area. Analyzed by clone and pyrosequencing libraries, genus
      Nitrosomonas was the predominant ammonia-oxidizing bacteria (AOB), but no ammonia
      oxidizing archaea (AOA) was abundant enough for sequencing in the activated
      sludge from the WWTPs; genus Nitrosomonas and Nitrosopumilus were the dominant
      AOB and AOA, respectively, in the coastal sediments. The different abundance of
      AOA but similar structure of AOB between the WWTPs and nearby coastal area
      probably indicated an anthropogenic impact on the microbial ecology in Hangzhou
      Bay. 

PMID- 25586578
TI  - Characterization of an omega-6 linoleate lipoxygenase from Burkholderia
      thailandensis and its application in the production of 13-hydroxyoctadecadienoic
      acid.
AB  - A recombinant putative lipoxygenase from Burkholderia thailandensis with a
      specific activity of 26.4 U mg(-1) was purified using HisTrap affinity
      chromatography. The native enzyme was a 75-kDa dimer with a molecular mass of 150
      kDa. The enzyme activity and catalytic efficiency (k cat/K m) were the highest
      for linoleic acid (k cat of 93.7 s(-1) and K m of 41.5 MUM), followed by
      arachidonic acid, alpha-linolenic acid, and gamma-linolenic acid. The enzyme was
      identified as an omega-6 linoleate lipoxygenase (or a linoleate 13S-lipoxygenase)
      based on genetic and HPLC analyses as well as substrate specificity. The reaction
      conditions for the enzymatic production of 13-hydroxy-9,11(Z,E)-octadecadienoic
      acid (13-HODE) were optimal at pH 7.5, 25  degrees C, 20 g l(-1) linoleic acid,
      2.5 g l(-1) enzyme, 0.1 mM Cu(2+), and 6% (v/v) methanol. Under these conditions,
      linoleate 13-lipoxygenase from B. thailandensis produced 20.8 g l(-1) 13-HODE
      (70.2 mM) from 20 g l(-1) linoleic acid (71.3 mM) for 120 min, with a molar
      conversion yield of 98.5% and productivity of 10.4 g l(-1) h(-1). The molar
      conversion yield and productivity of 13-HODE obtained using B. thailandensis
      lipoxygenase were 151 and 158% higher, respectively, than those obtained using
      commercial soybean lipoxygenase under the optimum conditions for each enzyme at
      the same concentrations of substrate and enzyme.

PMID- 25586579
TI  - Targeted expression of nuclear transgenes in Chlamydomonas reinhardtii with a
      versatile, modular vector toolkit.
AB  - We present a versatile vector toolkit for nuclear transgene expression in the
      model green microalga Chlamydomonas reinhardtii. The vector was designed in a
      modular fashion which allows quick replacement of regulatory elements and genes
      of interest. The current toolkit comprises two antibiotic resistance markers
      (paromomycin and hygromycin B), five codon-optimized light emission reporters,
      including the Gaussia princeps luciferase, as well as bright cyan, green, yellow,
      and red fluorescent protein variants. The system has demonstrated robust
      functional flexibility with signal options to target the protein of interest to
      the cytoplasm, the nucleus, cellular microbodies, the chloroplast, mitochondria,
      or via the endoplasmic reticulum-Golgi apparatus secretory pathway into the
      culture medium. Successful fluorescent reporter protein fusion to C. reinhardtii
      Rubisco small subunit 1 was accomplished with this system. Localization of the
      fluorescently tagged protein was observed in the chloroplast pyrenoid via live
      cell fluorescence microscopy, the first report of heterologous protein
      localization to this cellular structure. The functionalities of the vector
      toolkit, the individual modular elements, as well as several combinations thereof
      are demonstrated in this manuscript. Due to its strategic design, this vector
      system can quickly be adapted to individual tasks and should therefore be of
      great use to address specific scientific questions requiring nuclear recombinant
      protein expression in C. reinhardtii.

PMID- 25586580
TI  - The transcriptomic profile of Pseudozyma aphidis during production of
      mannosylerythritol lipids.
AB  - The basidiomycetous fungus Pseudozyma aphidis is able to convert vegetable oils
      to abundant amounts of the biosurfactant mannosylerythritol lipid (MEL) with a
      unique product pattern of MEL-A, MEL-B, MEL-C, and MEL-D. To investigate the
      metabolism of MEL production, we analyzed the transcriptome of P. aphidis DSM
      70725 under MEL-inducing and non-inducing conditions using deep sequencing.
      Following manual curation of the previously described in silico gene models based
      on RNA-Seq data, we were able to generate an experimentally verified gene
      annotation containing 6347 genes. Using this database, our expression analysis
      revealed that only four of the five cluster genes required for MEL synthesis were
      clearly induced by the presence of soybean oil. The acetyltransferase encoding
      gene PaGMAT1 was expressed on a much lower level, which may explain the secretion
      of MEL with different degrees of acetylation in P. aphidis. In parallel to MEL
      synthesis, microscopic observations showed morphological changes accompanied by
      expression of genes responsible for cell development, indicative of a
      coregulation between MEL synthesis and cell morphology. In addition a set of
      transcription factors was identified which may be responsible for regulation of
      MEL synthesis and cell development. The upregulation of genes required for
      nitrogen metabolism and other assimilation processes indicate additional
      metabolic pathways required under the MEL-inducing conditions used. We also
      searched for a conserved gene cluster for cellobiose lipids (CL) but only found
      seven genes with limited homology distributed over the genome. However, we
      detected characteristic TLC spots in fermentations using P. aphidis DSM 70725,
      indicative of CL secretion. 

PMID- 25586581
TI  - Truncation of domain V of the multidomain glucansucrase GTF180 of Lactobacillus
      reuteri 180 heavily impairs its polysaccharide-synthesizing ability.
AB  - Glucansucrases are exclusively found in lactic acid bacteria and synthesize a
      variety of alpha-glucans from sucrose. They are large multidomain enzymes
      belonging to the CAZy family 70 of glycoside hydrolase enzymes (GH70). The
      crystal structure of the N-terminal truncated GTF180 of Lactobacillus reuteri 180
      (GTF180-DeltaN) revealed that the polypeptide chain follows a U shape course to
      form five domains, including domains A, B, and C, which resemble those of family
      GH13 enzymes, and two extra and novel domains (domains IV and V), which are
      attached to the catalytic core. To elucidate the functional roles of domain V, we
      have deleted the domain V fragments from both the N- and C-terminal ends (GTF180
      DeltaNDeltaV). Truncation of domain V of GTF180-DeltaN yielded a catalytically
      fully active enzyme but with heavily impaired polysaccharide synthesis ability.
      Instead, GTF180-DeltaNDeltaV produced a large amount of oligosaccharides. Domain
      V is not involved in determining the linkage specificity, and the size of
      polysaccharide produced as the polysaccharide produced by GTF180-DeltaNDeltaV was
      identical in size and structure with that of GTF180-DeltaN. The data indicates
      that GTF180-DeltaNDeltaV acts nonprocessively, frequently initiating synthesis of
      a new oligosaccharide from sucrose, instead of continuing the synthesis of a full
      size polysaccharide. Mutations L940E and L940F in GTF180-DeltaNDeltaV, which are
      involved in the acceptor substrate binding, restored polysaccharide synthesis
      almost to the level of GTF180-DeltaN. These results demonstrated that
      interactions of growing glucan chains with both domain V and acceptor substrate
      binding sites are important for polysaccharide synthesis.

PMID- 25586583
TI  - Antimicrobial peptides: an alternative for innovative medicines?
AB  - Antimicrobial peptides are small molecules with activity against bacteria,
      yeasts, fungi, viruses, bacteria, and even tumor cells that make these molecules
      attractive as therapeutic agents. Due to the alarming increase of antimicrobial
      resistance, interest in alternative antimicrobial agents has led to the
      exploitation of antimicrobial peptides, both synthetic and from natural sources.
      Thus, many peptide-based drugs are currently commercially available for the
      treatment of numerous ailments, such as hepatitis C, myeloma, skin infections,
      and diabetes. Initial barriers are being increasingly overcome with the
      development of cost-effective, more stable peptides. Herein, we review the
      available strategies for their synthesis, bioinformatics tools for the rational
      design of antimicrobial peptides with enhanced therapeutic indices, hurdles and
      shortcomings limiting the large-scale production of AMPs, as well as the
      challenges that the pharmaceutical industry faces on their use as therapeutic
      agents. 

PMID- 25586582
TI  - A new salicylate synthase AmS is identified for siderophores biosynthesis in
      Amycolatopsis methanolica 239(T).
AB  - Siderophores are important for the growth of bacteria or the applications in
      treatment of iron overload-associated diseases due to the iron-chelating
      property. Salicylate synthase played a key role in the biosynthesis of some NRPS
      derived siderophores by the providing of an iron coordination moiety as the
      initial building block. A new salicylate synthase, namely AmS, was identified in
      the biosynthesis pathway of siderophore amychelin in Amycolatopsis methanolica
      239(T), since it shunt chorismate, an integrant precursor, from primary to
      secondary metabolite flow. The amino acid sequence alignment and phylogenetic
      analysis showed that AmS grouped into a new cluster. In vitro assays of AmS
      revealed its wide temperature tolerance ranged from 0 to 40  degrees C and narrow
      pH tolerant ranged from 7.0 to 9.0. AmS was resistant to organic solvents and non
      ionic detergents. Moreover, AmS converted chorismate to salicylate with K m of
      129.05 MUM, k cat of 2.20 min(-1) at optimal conditions, indicating its low
      substrate specificity and comparable velocity to reported counterparts (Irp9 and
      MbtI). These properties of AmS may improve the iron-seizing ability of A.
      methanolica to compete with its neighbors growing in natural environments. Most
      importantly, serine and cysteine residues were found to be important for the
      catalytic activity of AmS. This study presented AmS as a new cluster of
      salicylate synthase and the reaction mechanism and potential applications of
      salicylate synthase were highlighted as well.

PMID- 25586584
TI  - Genomic and chemical insights into biosurfactant production by the mangrove
      derived strain Bacillus safensis CCMA-560.
AB  - Many Bacillus species can produce biosurfactant, although most of the studies on
      lipopeptide production by this genus have been focused on Bacillus subtilis.
      Surfactants are broadly used in pharmaceutical, food and petroleum industry, and
      biological surfactant shows some advantages over the chemical surfactants, such
      as less toxicity, production from renewable, cheaper feedstocks and development
      of novel recombinant hyperproducer strains. This study is aimed to unveil the
      biosurfactant metabolic pathway and chemical composition in Bacillus safensis
      strain CCMA-560. The whole genome of the CCMA-560 strain was previously
      sequenced, and with the aid of bioinformatics tools, its biosurfactant metabolic
      pathway was compared to other pathways of closely related species. Fourier
      transform infrared (FTIR) and high-resolution TOF mass spectrometry (MS) were
      used to characterize the biosurfactant molecule. B. safensis CCMA-560 metabolic
      pathway is similar to other Bacillus species; however, some differences in amino
      acid incorporation were observed, and chemical analyses corroborated the genetic
      results. The strain CCMA-560 harbours two genes flanked by srfAC and srfAD not
      present in other Bacillus spp., which can be involved in the production of the
      analogue gramicidin. FTIR and MS showed that B. safensis CCMA-560 produces a
      mixture of at least four lipopeptides with seven amino acids incorporated and a
      fatty acid chain with 14 carbons, which makes this molecule similar to the
      biosurfactant of Bacillus pumilus, namely, pumilacidin. This is the first report
      on the biosurfactant production by B. safensis, encompassing the investigation of
      the metabolic pathway and chemical characterization of the biosurfactant
      molecule. 

PMID- 25586585
TI  - Engineering of Escherichia coli for the biosynthesis of poly(3-hydroxybutyrate-co
      3-hydroxyhexanoate) from glucose.
AB  - The copolymer poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(HB-co-HHx)] has
      the potential to serve as a biodegradable tissue engineering material. However,
      the production of this kind of copolymer still suffers from high cost and
      uncertainty. We describe here the design of metabolic pathways to synthesize P(HB
      co-HHx) directly from glucose using recombinant Escherichia coli. By combining
      the BktB-dependent condensation pathway with the inverted beta-oxidation cycle
      pathway, we were able to synthesize a P(HB-co-HHx) copolymer with a 10 mol% HHx
      fraction in recombinant E. coli. After optimizing the host strain and employing
      thioesterase mutant strains, the engineered E. coli produced 12.9 wt% P(HB-co
      HHx) with a 13.2 mol% 3HHx fraction.

PMID- 25586586
TI  - The herbal-derived honokiol and magnolol enhances immune response to infection
      with methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant
      S. aureus (MRSA).
AB  - The emergence of antibiotic resistant strains such as methicillin-resistant
      Staphylococcus aureus (MRSA) reminds us an urgent need to develop a new immune
      modulating agent for preventing S. aureus infection. In this study, we found that
      herbal medicines, honokiol and magnolol, caused a significant cellular immune
      modulatory effect during S. aureus infection. In mouse macrophages, these
      compounds drove upregulation of an antioxidant effect in response to S. aureus,
      resulting in a dampened total cellular reactive oxygen species (ROS) production
      and decreased production of inflammatory cytokines/chemokines, whereas honokiol
      induced increased types I and III interferon messenger RNA (mRNA) expression
      levels in response to MSSA infection. Moreover, the internalization of S. aureus
      by human alveolar epithelial cells was inhibited by these compounds. Furthermore,
      honokiol and magnolol treatment promoted a delay in killing during MSSA infection
      in Caenorhabditis elegans, suggesting antimicrobial function in vivo. In
      conclusion, honokiol and magnolol may be considered as attractive immune
      modulating treatment for S. aureus infection. 

PMID- 25586587
TI  - Chimpanzees (Pan troglodytes) and human children (Homo sapiens) know when they
      are ignorant about the location of food.
AB  - Over the last decade, the metacognitive abilities of nonhuman primates and the
      developmental emergence of metacognition in children have become topics of
      increasing research interest. In the current study, the performance of three
      adult chimpanzees (Pan troglodytes; Experiment 1) and forty-four 3.5- and 5.5
      year-old human children (Experiment 2) was assessed on a behavioral search
      paradigm designed to assess metacognition. Subjects either directly observed the
      baiting of a large reward into one cup among an array of four, or had the baiting
      occluded from their view. In half of the trials, subjects were also presented
      with an additional distinctive cup that was always visibly baited with a small
      reward. This cup allowed subjects the opportunity to escape from making a guess
      about the location of the bigger reward. All three chimpanzees and both age
      groups of children selected the escape cup more often when the baiting of the
      large reward was concealed, compared to when it was visible. This demonstrates
      that both species can selectively choose a guaranteed smaller reward when they do
      not know the location of a larger reward and provides insight into the
      development of metacognition.

PMID- 25586588
TI  - Osteogenic responses to zirconia with hydroxyapatite coating by aerosol
      deposition.
AB  - Previously, we found that osteogenic responses to zirconia co-doped with niobium
      oxide (Nb2O5) or tantalum oxide (Ta2O5) are comparable with responses to
      titanium, which is widely used as a dental implant material. The present study
      aimed to evaluate the in vitro osteogenic potential of hydroxyapatite (HA)-coated
      zirconia by an aerosol deposition method for improved osseointegration. Surface
      analysis by scanning electron microscopy and x-ray diffraction proved that a thin
      as-deposited HA film on zirconia showed a shallow, regular, crater-like surface.
      Deposition of dense and uniform HA films was measured by SEM, and the contact
      angle test demonstrated improved wettability of the HA-coated surface. Confocal
      laser scanning microscopy indicated that MC3T3-E1 pre-osteoblast attachment did
      not differ notably between the titanium and zirconia surfaces; however, cells on
      the HA-coated zirconia exhibited a lower proliferation than those on the uncoated
      zirconia late in the culture. Nevertheless, ALP, alizarin red S staining, and
      bone marker gene expression analysis indicated good osteogenic responses on HA
      coated zirconia. Our results suggest that HA-coating by aerosol deposition
      improves the quality of surface modification and is favorable to osteogenesis. 

PMID- 25586589
TI  - Erythropoietin promotes bone formation through EphrinB2/EphB4 signaling.
AB  - Recent studies have demonstrated that erythropoietin (EPO) has extensive
      nonhematopoietic biological functions. However, little is known about how EPO
      regulates bone formation, although several studies suggested that EPO can affect
      bone homeostasis. In this study, we investigated the effects of EPO on the
      communication between osteoclasts and osteoblasts through the ephrinB2/EphB4
      signaling pathway. We found that EPO slightly promotes osteoblastic
      differentiation with the increased expression of EphB4 in ST2 cells. However, EPO
      increased the expression of Nfatc1 and ephrinB2 but decreased the expression of
      Mmp9 in RAW264.7 cells, resulting in an increase of ephrinB2-expressing
      osteoclasts and a decrease in resorption activity. The stimulation of
      ephrinB2/EphB4 signaling via ephrinB2-Fc significantly promoted EPO-mediated
      osteoblastic differentiation in ST2 cells. EphB4 knockdown through EphB4 shRNA
      inhibited EPO-mediated osteoblastic phenotypes. Furthermore, in vivo assays
      clearly demonstrated that EPO efficiently induces new bone formation in the
      alveolar bone regeneration model. Taken together, these results suggest that
      ephrinB2/EphB4 signaling may play an important role in EPO-mediated bone
      formation. 

PMID- 25586592
TI  - Chlorin e6-ZnSe/ZnS quantum dots based system as reagent for photodynamic
      therapy.
AB  - Stable water-soluble complexes of Cd-free ZnSe/ZnS quantum dots (QDs) and chlorin
      e6 complexes have been prepared. These complexes have shown approximately 50%
      intracomplex fluorescence resonance energy transfer from QDs to chlorin e6. The
      photodynamic therapy (PDT) test of the complexes against the Erlich acsite
      carcinoma cell culture demonstrated a two-fold enhancement of the cancer cell
      photodynamic destruction as compared to that of free chlorin e6 molecules. It was
      shown that the PDT effect was significantly increased due to two factors: the
      efficient QD-chlorin e6 photoexcitation energy transfer and the improvement of
      cellular uptake of the photosensitizer in the presence of ZnSe/ZnS QDs. 

PMID- 25586591
TI  - Identification of Toxoplasma gondii antigens associated with different types of
      infection by serum antibody profiling.
AB  - Acquisition of acute toxoplasmosis during the first trimester of pregnancy can
      have catastrophic consequences for the foetus. Diagnosis is routinely based on
      the detection of maternal Toxoplasma gondii--antibodies using whole parasite
      extracts as detection antigen. While such assays are sensitive, they show no
      specificity for the stage of infection. We hypothesized diagnosis might be
      improved using recombinant antigens for detection, particularly if antibodies to
      certain antigen(s) were associated with early or late stages of infection. To
      address this, protein microarrays comprising 1513 T. gondii exon products were
      probed with well-characterized sera from seronegative ('N') controls, and acute
      ('A'), chronic/IgM-persisting ('C/M') and chronic ('C') toxoplasmosis cases from
      Turkey. Three reactive exon products recognized preferentially in A infections,
      and three recognized preferentially in C/M infections, were expressed in
      Escherichia coli and tested for discrimination in IgG ELISAs. The best
      discriminators were exon 1 of TGME49_086450 (GRA5) which detected C/M infections
      with 70.6% sensitivity and 81.8% specificity, and exon 6 of TGME49_095700
      (ubiquitin transferase domain-containing protein) which detected A infections
      with 84.8% sensitivity and 82.4% specificity. Overall, the data support a
      recombinant protein approach for the development of improved serodiagnostic tests
      for toxoplasmosis.

PMID- 25586594
TI  - Action spectroscopy of a protonated peptide in the ultraviolet range.
AB  - Action spectroscopy of protonated substance P, a model undecapeptide, has been
      probed from 5.2 eV to 20 eV. For photon energy above the ionization threshold
      measured at 10.3 +/- 0.1 eV, the radical dication is observed along with side
      chain losses and abundant formation of all kinds of sequence ions. Below the
      photoionization threshold, the photoproducts involve side chain cleavages and
      backbone cleavages into a-, b-/y-, and c-sequence ions. Different electronic
      excited states appear to produce different fragment ions. Norrish type I and II
      reactions are proposed to account for some photoproducts. This study bridges the
      gap between laser activation and electron-induced dissociation of peptides.
      Moreover, our results report for the first time a comprehensive picture of the
      photochemical fragmentation of a gas phase peptide in a wide photon energy range.

PMID- 25586596
TI  - Novel method for rapid reversal of drug toxicity: a case report.
AB  - Drug toxicity is traditionally treated by reducing the amount of the drug
      absorbed, enhancing elimination, and providing supportive care. Once the drug has
      been absorbed, there are few methods that help decrease morbidity and mortality
      caused by a toxic drug level. Albumin infusion is a new approach that changes
      that, as it can rapidly reverse a toxic drug level back to a therapeutic level.
      It is believed with most drugs that the toxic effects are related to the total
      amount of the free drug. In this method, albumin binds to the free drug and acts
      as a reservoir or depot from which the drug is slowly released to the free form,
      thereby limiting the effects of drug toxicity. In this case report, an elderly
      female patient who experienced phenytoin toxicity was treated with albumin
      infusion, after which her phenytoin level returned to a therapeutic level with
      corresponding improvements in her symptoms. Based on our calculations, it was
      predicted that a small amount of albumin would reverse the patient's toxic
      symptoms. With this approach, the patient's toxic symptoms improved when free
      phenytoin levels dropped from 15 to 8 MUmol/L. Albumin infusion is a promising
      new therapy that can rapidly reverse a toxic drug level back to a therapeutic
      level by binding the free drug to albumin.

PMID- 25586597
TI  - Educating surgeons on intraoperative disposable supply costs during laparoscopic
      cholecystectomy: a regional health system's experience.
AB  - BACKGROUND: Surgeons play a crucial role in the cost efficiency of the operating
      room through total operative time, use of supplies, and patient outcomes. This
      study aimed to examine the effect of surgeon education on disposable supply usage
      during laparoscopic cholecystectomy. METHODS: Surgeons were educated about the
      cost of disposable equipments without incentives for achieved cost reductions.
      Surgical supply costs for laparoscopic cholecystectomy in fiscal year (FY) 2013
      were compared with FY 2014. RESULTS: The average disposable supply cost per
      laparoscopic cholecystectomy was reduced from $589 (n = 586) in FY 2013 to $531
      (n = 428) in FY 2014, representing a 10% reduction in supply costs (P < .001).
      Adjustments included reduction in the use of expensive fascial closure devices,
      clip appliers, suction irrigators, and specimen retrieval bags. CONCLUSIONS:
      Disposable equipment cost for laparoscopic cholecystectomy can be reduced by
      surgeon education. These techniques can likely be used to reduce costs in an
      array of specialties and procedures.

PMID- 25586593
TI  - Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant
      myelodysplastic syndrome.
AB  - Somatic mutations in the spliceosome gene ZRSR2-located on the X chromosome-are
      associated with myelodysplastic syndrome (MDS). ZRSR2 is involved in the
      recognition of 3'-splice site during the early stages of spliceosome assembly;
      however, its precise role in RNA splicing has remained unclear. Here we
      characterize ZRSR2 as an essential component of the minor spliceosome (U12
      dependent) assembly. shRNA-mediated knockdown of ZRSR2 leads to impaired splicing
      of the U12-type introns and RNA-sequencing of MDS bone marrow reveals that loss
      of ZRSR2 activity causes increased mis-splicing. These splicing defects involve
      retention of the U12-type introns, while splicing of the U2-type introns remain
      mostly unaffected. ZRSR2-deficient cells also exhibit reduced proliferation
      potential and distinct alterations in myeloid and erythroid differentiation in
      vitro. These data identify a specific role for ZRSR2 in RNA splicing and
      highlight dysregulated splicing of U12-type introns as a characteristic feature
      of ZRSR2 mutations in MDS. 

PMID- 25586598
TI  - Prediction models of Medicare 90-day postdischarge deaths, readmissions, and
      costs in bowel operations.
AB  - BACKGROUND: The 90-day postdischarge morbidity and mortality rates following
      elective and emergent bowel surgery remain poorly defined. METHODS: The 2009 to
      2011 Medicare inpatient files for patients undergoing elective and emergent small
      and large bowel operations in 1,024 hospitals that passed present-on-admission
      coding accuracy standards had prediction models designed for inpatient mortality,
      prolonged postoperative length of hospital stay (prLOS), 90-day postdischarge
      mortality and readmissions, and total hospital costs. RESULTS: Of 118,758
      patients studied, there was a 4.7% inpatient mortality rate and 7.3% prLOS among
      live discharges. An additional 7,586 deaths and 26,969 readmissions occurred
      within 90 days of discharge. Prolonged preoperative and prolonged postoperative
      hospitalizations were significant (P < .0001) variables in predicting
      postdischarge deaths and readmissions. Total hospital costs were increased by
      over $18,000 per adverse outcome. CONCLUSION: Postdischarge deaths and
      readmissions are more common than inpatient adverse events of death and prLOS in
      elective and emergent Medicare large and small bowel operations.

PMID- 25586599
TI  - The derived neutrophil/lymphocyte ratio predicts poor clinical outcome in soft
      tissue sarcoma patients.
AB  - BACKGROUND: Inflammation plays an important role in tumor proliferation and
      survival in cancer patients. The aim of this study was to investigate the
      prognostic impact of the pre-operative-derived neutrophil/lymphocyte ratio (dNLR)
      in a large cohort of soft tissue sarcoma (STS) patients after curative surgical
      resection. METHODS: The impact of preoperative dNLR on disease-free survival
      (DFS) and overall survival (OS) in retrospectively evaluated 340 STS patients was
      assessed using Kaplan-Meier curves and Cox proportional models. RESULTS: Applying
      receiver operating curve analysis, we determined a cut-off value of 2.39 for the
      dNLR to be optimal for discrimination of patients' survival in the whole cohort.
      Kaplan-Meier curves revealed a dNLR greater than or equal to 2.39 as a marker for
      decreased DFS (P = .031) and OS (P = .007, log-rank test) in STS patients. In
      multivariate analysis, increased dNLR was significantly associated with poor OS
      (hazard ratio 1.60, 95% confidence interval 1.07 to 2.40, P = .022). CONCLUSIONS:
      This study demonstrates that preoperative dNLR might represent a well-correlated
      surrogate marker for the widely validated NLR. The dNLR is easily obtainable and
      can provide important information for individual risk assessment in clinical
      trials.

PMID- 25586600
TI  - Real-time web-based assessment of total population risk of future emergency
      department utilization: statewide prospective active case finding study.
AB  - BACKGROUND: An easily accessible real-time Web-based utility to assess patient
      risks of future emergency department (ED) visits can help the health care
      provider guide the allocation of resources to better manage higher-risk patient
      populations and thereby reduce unnecessary use of EDs. OBJECTIVE: Our main
      objective was to develop a Health Information Exchange-based, next 6-month ED
      risk surveillance system in the state of Maine. METHODS: Data on electronic
      medical record (EMR) encounters integrated by HealthInfoNet (HIN), Maine's Health
      Information Exchange, were used to develop the Web-based surveillance system for
      a population ED future 6-month risk prediction. To model, a retrospective cohort
      of 829,641 patients with comprehensive clinical histories from January 1 to
      December 31, 2012 was used for training and then tested with a prospective cohort
      of 875,979 patients from July 1, 2012, to June 30, 2013. RESULTS: The
      multivariate statistical analysis identified 101 variables predictive of future
      defined 6-month risk of ED visit: 4 age groups, history of 8 different encounter
      types, history of 17 primary and 8 secondary diagnoses, 8 specific chronic
      diseases, 28 laboratory test results, history of 3 radiographic tests, and
      history of 25 outpatient prescription medications. The c-statistics for the
      retrospective and prospective cohorts were 0.739 and 0.732 respectively.
      Integration of our method into the HIN secure statewide data system in real time
      prospectively validated its performance. Cluster analysis in both the
      retrospective and prospective analyses revealed discrete subpopulations of high
      risk patients, grouped around multiple "anchoring" demographics and chronic
      conditions. With the Web-based population risk-monitoring enterprise dashboards,
      the effectiveness of the active case finding algorithm has been validated by
      clinicians and caregivers in Maine. CONCLUSIONS: The active case finding model
      and associated real-time Web-based app were designed to track the evolving nature
      of total population risk, in a longitudinal manner, for ED visits across all
      payers, all diseases, and all age groups. Therefore, providers can implement
      targeted care management strategies to the patient subgroups with similar
      patterns of clinical histories, driving the delivery of more efficient and
      effective health care interventions. To the best of our knowledge, this
      prospectively validated EMR-based, Web-based tool is the first one to allow real
      time total population risk assessment for statewide ED visits.

PMID- 25586603
TI  - Novel mutations in the von Hippel-Lindau gene associated with congenital
      polycythemia.

PMID- 25586601
TI  - PD-1 blockade therapy in renal cell carcinoma: current studies and future
      promises.
AB  - RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell
      infiltrate, unable to control tumor growth. Evasion of immune surveillance, a
      process defined immune-editing, leads to malignant progression. The striking
      improvement of knowledge in immunology has led to the identification of immune
      checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor
      immunity. The interaction between PD-1, an inducible inhibitory receptor
      expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells,
      results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1
      axis inhibition by targeted-antibodies, increasing the T-cell proliferation and
      cytotoxicity, represents a promising mechanism to stimulate the anti-tumor
      activity of the immune system, improving the outcomes of cancer patients. Several
      PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing
      promising results. The interesting correlation between lymphocytes PD-1
      expression and RCC advanced stage, grade and prognosis, as well as the selective
      PD-L1 expression by RCC tumor cells and its potential association with worse
      clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents,
      alone or in combination with anti-angiogenic drugs or other immunotherapeutic
      approaches, for the treatment of RCC. In this review we discuss the role of PD
      1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies
      and promising therapeutic perspectives to target the PD-1 pathway. 

PMID- 25586604
TI  - Concomitant bone marrow involvement by plasma cell myeloma and primary
      myelodysplastic syndrome with biclonal complex chromosome anomalies.

PMID- 25586602
TI  - Cause or Effect? Selective Serotonin Reuptake Inhibitors and Falls in Older
      Adults: A Systematic Review.
AB  - A 2012 update of the Beers criteria categorizes selective serotonin reuptake
      inhibitors (SSRIs) as potentially inappropriate medications in all older adults
      based on fall risk. The application of these recommendations, not only to frail
      nursing home residents, but to all older adults, may lead to changes in health
      policy or clinical practice with harmful consequences. A systematic review of
      studies on the association between SSRIs and falls in older adults was conducted
      to examine the evidence for causation. Twenty-six studies met the inclusion
      criteria. The majority of studies were observational and suggest an association
      between SSRIs and falls. The direction of the relationship--causation or effect-
      cannot be discerned from this type of study. Standardized techniques for
      determining likely causation were then used to see if there was support for the
      hypothesis that SSRIs lead to falls. This analysis did not suggest causation was
      likely. There is no Level 1 evidence that SSRIs cause falls. Therefore, changes
      in the current treatment guidelines or policies on the use of SSRIs in older
      adults based on fall risk may not be justified at this time given the lack of an
      established evidence base. Given its significance to public health, well-designed
      experimental studies are required to address this question definitively.

PMID- 25586606
TI  - Nurse like cells: chronic lymphocytic leukemia associated macrophages.
AB  - CD14 + cells are able to differentiate into large and adherent cells if in
      contact with chronic lymphocytic leukemia (CLL) cells or healthy B lymphocytes.
      In CLL these cells, called CLL-nurse like cells (NLCs), express a very high
      amount of CD163 and CD68 and are able to rescue CLL cells through CCL4
      production. Adherent cells derived from healthy donors, called HD-NLCs, express
      very little CD163 and CD68, do not produce CCL4 and are unable to rescue CCL
      cells. This study reveals that CLL-NLCs are the specific nurse cells in CLL,
      protecting CLL cells from death. 

PMID- 25586605
TI  - Asparaginase pharmacokinetics and implications of therapeutic drug monitoring.
AB  - Asparaginase is widely used in chemotherapeutic regimens for the treatment of
      acute lymphoblastic leukemia (ALL) and has led to a substantial improvement in
      cure rates, especially in children. Optimal therapeutic effects depend on a
      complete and sustained depletion of serum asparagine. However, pronounced
      interpatient variability, differences in pharmacokinetic properties between
      asparaginases and the formation of asparaginase antibodies make it difficult to
      predict the degree of asparagine depletion that will result from a given dose of
      asparaginase. The pharmacological principles underlying asparaginase therapy in
      the treatment of ALL are summarized in this article. A better understanding of
      the many factors that influence asparaginase activity and subsequent asparagine
      depletion may allow physicians to tailor treatment to the individual, maximizing
      therapeutic effect and minimizing treatment-related toxicity. Therapeutic drug
      monitoring provides a means of assessing a patient's current depletion status and
      can be used to better evaluate the potential benefit of treatment adjustments. 

PMID- 25586607
TI  - Selective Janus associated kinase 1 inhibition as a therapeutic target in
      myelofibrosis.
AB  - Hyperactive Janus associated kinase-signal transducers and activators of
      transcription (JAK-STAT) signaling has been shown to be integral to the
      pathogenesis of myelofibrosis (MF) regardless of the driver mutational status
      (JAK2V617F, JAK2 exon 12, MPL515L/K, CALR). Targeting of the JAK-STAT pathway has
      been the intense focus of therapeutic development and led to the approval of the
      JAK1/2 inhibitor, ruxolitinib. Despite the clear clinical success of ruxolitinib,
      dose limiting thrombocytopenia, treatment associated anemia and failure to
      effectively achieve bone marrow pathologic, cytogenetic and molecular remission
      remain shortcomings. JAK1 inhibition leads to depression in inflammatory cytokine
      expression associated with MF-related constitutional symptoms. The selective
      targeting of JAK1 may provide an opportunity to alleviate MF-related symptoms
      without anti-JAK2 therapy-related myelosuppression. Additionally, a JAK1
      inhibitor may serve as an ideal candidate partner for combination therapeutic
      approaches in the treatment of MF. Current evaluation of selective JAK1
      inhibition in MF will further clarify the relative contribution of aberrant JAK1
      signaling to the pathogenesis of MF. 

PMID- 25586608
TI  - Epigenetic regulation of microRNA expression in Hodgkin lymphoma.
AB  - Epigenetic mechanisms are crucial for the inactivation of key genes related to
      the survival of Hodgkin lymphoma (HL) cells, and methylation is a frequent
      epigenetic mechanism of microRNA silencing. We have examined the methylation
      induced silencing of tumor suppressor microRNAs in HL cell lines and confirmed
      our results in patient lymph nodes. In addition, we evaluated the in vitro
      effectiveness of 5-aza-2-deoxycytidine (5-Aza-dC) in HL cell lines. Ten microRNAs
      containing CpG islands in their promoter region were re-expressed in both the L
      428 and L-1236 cell lines. Interestingly, miR-34a and miR-203, both known tumor
      suppressor microRNAs, were found to be methylated in cell lines and in patient
      samples. 5-Aza-dC treatment resulted in a dose-dependent antiproliferative effect
      at 72 h in all the HL cell lines. In summary, 5-Aza-dC treatment of HL cell lines
      inhibits proliferation at high doses and produces re-expression of the tumor
      suppressor microRNAs at low-intermediate doses. 

PMID- 25586609
TI  - "Heterogeneity within order" in metal-organic frameworks.
AB  - Metal-organic frameworks (MOFs) are constructed by linking inorganic units with
      organic linkers to make extended networks. Though more than 20 000 MOF structures
      have been reported most of these are ordered and largely composed of a limited
      number of different kinds building units, and very few have multiple different
      building units (heterogeneous). Although heterogeneity and multiplicity is a
      fundamental characteristic of biological systems, very few synthetic materials
      incorporate heterogeneity without losing crystalline order. Thus, the question
      arises: how do we introduce heterogeneity into MOFs without losing their ordered
      structure? This Review outlines strategies for varying the building units within
      both the backbone of the MOF and its pores to produce the heterogeneity that is
      sought after. The impact this heterogeneity imparts on the properties of a MOF is
      highlighted. We also provide an update on the MOF industry as part of this themed
      issue for the 150th anniversary of BASF. 

PMID- 25586610
TI  - Changes in the contents of selected polycyclic aromatic hydrocarbons in soils of
      various types.
AB  - The aim of the paper was to determine the stability and the decomposition
      intensity of selected polycyclic aromatic hydrocarbons (fluorene, anthracene,
      pyrene, and chrysene) in soils that are under agricultural use. Soil was sampled
      from the arable layer that is representative of the Kujawy and Pomorze Provinces,
      which are located in the northwestern part of Poland. The soil samples were
      polluted with selected PAHs at an amount corresponding to 10 mg PAHs/kg. PAH
      polluted soil samples were incubated for 10, 30, 60, 120, 180, and 360 days at a
      temperature of 20-25  degrees C and a fixed moisture of 50% field water capacity.
      High-performance liquid chromatography (HPLC) was used to determine the content
      of PAHs. It was found that the process of the degradation of PAHs was most
      intensive during the first 30 days of the experiment; however, three-ring PAHs
      (fluorene and anthracene) definitely decomposed faster than the four-ring ones
      (pyrene and chrysene). The results also confirm the significant role of soil
      organic matter in sorption and activation processes of PAHs.

PMID- 25586611
TI  - Particulate matter concentration and chemical composition in the metro system of
      Rome, Italy.
AB  - Air quality at the main station of the metro system of Rome (Termini hub) has
      been characterized by the point of view of particulate matter (PM) concentration
      and chemical composition. Indoor air in different environments (underground train
      platform and shopping center, metro carriages with and without air conditioning
      system) has been studied and compared with outdoor air at a nearby urban site.
      Air quality at the railway station, located outdoor at surface level, has been
      also considered for comparison. PM chemical characterization included ions,
      elemental carbon, organic carbon, macro-elements, and the bio-accessible and
      residual fractions of micro- and trace elements. Train platform and carriages
      without air conditioning resulted to be the most polluted environments, with
      indoor/outdoor ratio up to two orders of magnitude for many components. PM mass
      concentration was determined on filter membranes by the gravimetric procedure as
      well as from the optical particle counter (OPC) number concentration
      measurements. The OPC results, taken with the original calibration factor, were
      below 40 % of the value obtained by the gravimetric measurements. Only a chemical
      and morphological characterization of the collected dust could lead to a
      reconciliation of the results yielded by the two methods. Macro-components were
      used to estimate the strength of the main macro-sources. The most significant
      contribution is confirmed to derive from wheels, rails, and brakes abrasion; from
      soil re-suspension (over 50 % at the subway platform); and from organics (about
      25 %). The increase in the concentration of elements was mostly due to the
      residual fraction, but also the bio-accessible fraction showed a remarkable
      enrichment, particularly in the case of Ba, Zn, Cd, and Ni.

PMID- 25586612
TI  - Uptake and speciation of vanadium in the rhizosphere soils of rape (Brassica
      juncea L.).
AB  - The response of rape (Brassica juncea L.) to different vanadium (V) speciation in
      rhizosphere soils was investigated in pot experiments using an agricultural soil
      containing 147 mg V kg(-1) supplemented with 0-500 mg V kg(-1) of pentavalent V
      [V(V)] and a mining soil containing 774 mg V kg(-1). Tetravalent V [V(IV)]
      accounted for 76.1 and 85.9 % of total V in the untreated agricultural soil and
      mining soil, respectively. The proportion of both V(V) and water-extractable V
      increased with increasing concentrations of V(V) in the agricultural soil. The
      growth of rape substantially reduced the concentrations of V(V) but not V(IV) in
      the rhizosphere soil, suggesting that V(V) was actively involved in the soil-rape
      interaction of V. Both soil V(V) and water-extractable V were negatively related
      to the total rape biomass, but were positively correlated with the concentration
      of root V. No such relationships were found for total V and soil V(IV). Together,
      these results indicate that soil V(V) and water-extractable V might better
      reflect the toxicity of V in soils than total V and soil V(IV). Rape accumulated
      V in the sequence: roots > > stem > leaf > seed. As indicated by the remarkably
      low root bioconcentration factor of V(V) (0.41-7.24 %), rape had a lower ability
      to accumulate V than other plants reported in the literature (14.6-298 %). Only a
      small fraction of V in rape roots was translocated to the aboveground organs (the
      translocation factor was 3.57-46.9 %). No V was detectable in seeds in the soils
      at 147 and 197 mg V kg(-1), and no seed was produced in the soils at higher V
      concentrations. Thus, the risk of V intake by humans via the consumption of
      rapeseed-based foods under normal conditions is considered to be lower than that
      of other plants.

PMID- 25586613
TI  - Cytotoxicity of zinc nanoparticles fabricated by Justicia adhatoda L. on root
      tips of Allium cepa L.--a model approach.
AB  - Zinc nanoparticles were synthesized using aqueous leaf extract of Justicia
      adhatoda L. The characterization of nanoparticles was done by ultraviolet-visible
      (UV-vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, atomic
      force microscopy (AFM), and high-resolution transmission electron microscopy (HR
      TEM). The characteristic absorption peak of the UV spectrum was recorded at 379
      nm. The FTIR data revealed the possible biomolecules involved in bioreduction and
      capping of zinc nanoparticles for efficient stabilization. AFM and HR-TEM images
      have shown that the size of zinc nanoparticles ranges from 55 to 83 nm and they
      are spherical in shape. The biogenic zinc nanoparticles were evaluated for their
      toxic effect on mitotic chromosomes of Allium cepa as a model system. Experiments
      were conducted in triplicate to assay the effect of 25, 50, 75, and 100 % of zinc
      nanoparticles on mitotic chromosomes at an interval of 6 h duration for 24 h. The
      investigation revealed that the mitotic index (MI) was decreased with increased
      concentration of zinc nanoparticles and exposure duration. The results revealed
      that zinc nanoparticles have induced abnormalities like anaphase bridge
      formation, diagonal anaphase, C-metaphase, sticky metaphase, laggards, and sticky
      anaphase at different percentages and times of exposure. It is evident from the
      observation that mitotic cell division becomes abortive at 100 % treatment of
      zinc nanoparticles. 

PMID- 25586615
TI  - Performance of a wall cascade constructed wetland treating surfactant-polluted
      water.
AB  - Carwashes are highly water-consuming processes that require wastewater treatment
      before discharge into a sewer system due to the complex composition of leachate.
      Anionic surfactants (AS) are the main constituents of this wastewater because of
      their cleaning and solubilization properties; they can be potentially dangerous
      for the environment if not adequately treated. Constructed wetlands (CWs) are low
      cost systems increasingly used to treat different types of wastewater; however,
      there are few studies on their use for the treatment of carwash wastewater. In
      this study, an innovative constructed wetland arranged in a "cascade" to simulate
      a wall system (WCCW) was experimented in 2010 and 2011 to treat AS. Three plant
      species were tested at different AS inlet concentrations (10, 50, and 100 mg L(
      1)) with two hydraulic retention times (HRTs; 3 and 6 days): ribbon grass
      (Typhoides arundinacea (L.) Moench (syn. Phalaris arundinacea L.) var. picta;
      Ta), water mint (Mentha aquatica L.; Ma), and divided sedge (Carex divisa Hudson;
      Cd). All plant species grew constantly over the experimental period, showing a
      capacity to tolerate even the highest AS concentration. Using the HRT of 6 days,
      raising the inlet concentration increased the AS outlet concentration, with
      similar values for the treatments (median values of 0.13-0.15, 0.47-0.78, and
      1.19-1.46 mg L(-1) at inlet concentrations in the order 10, 50, and 100 mg L(
      1)). The shorter HRT led to significant differences among treatments in the
      reduction of outlet concentration, the best result being given by the tanks
      vegetated with Ma (A = 97.7 % with outlet concentration 0.35 mg L(-1)). After
      treatments of the WCCW, the AS content was reduced almost completely, with
      removal in the ranges 0.07-10.2 g m(-2) day(-1) for tanks planted with Ta, 0.10
      9.1 g m(-2) day(-1) for Ma tanks, and 0.11-9.5 g m(-2) day(-1) for Cd tanks
      depending on the inlet concentration. 

PMID- 25586616
TI  - Using stable isotope analysis in stream mesocosms to study potential effects of
      environmental chemicals on aquatic-terrestrial subsidies.
AB  - While recent research has provided evidence that the emergence of merolimnic
      insects (species with an aquatic larval stage) provides a considerable energy
      subsidy to riparian food webs, it has also shown that merolimnic insects may
      serve as a vector for contaminants. Therefore, riparian food webs may be at risk
      from either an aquatic-terrestrial transfer of contaminants or from the
      contaminant-driven reductions of emerging merolimnic insects. The objective of
      the present study was to develop an integrated stream mesocosms test design
      capable of identifying these inter-ecosystem boundary effects and to provide a
      comprehensive approach as a basis for ecotoxicological testing. We chose the
      widely distributed web-building spider Tetragnatha extensa as a representative
      species for riparian predators. Trophic aspects of riparian food webs were
      investigated by stable isotope analysis of carbon (delta(13)C) and nitrogen
      (delta(15)N). Utilization of stable isotope ratios provided detailed information
      on the riparian food web structure and the dietary composition of T. extensa.
      Merolimnic invertebrates (mainly Cloeon spp. and Chironomidae) were found to
      contribute up to 71 % of T. extensa's diet, demonstrating their importance in
      riparian food webs in ecotoxicological mesocosm testing. This study provides a
      conceptual and methodological basis for assessing aquatic insect emergence
      related pollutant transfer or effect translation from aquatic to adjacent
      terrestrial systems. 

PMID- 25586614
TI  - Exercise protects against PCB-induced inflammation and associated cardiovascular
      risk factors.
AB  - Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that
      contribute to the initiation of cardiovascular disease. Exercise has been shown
      to reduce the risk of cardiovascular disease; however, whether exercise can
      modulate PCB-induced vascular endothelial dysfunction and associated
      cardiovascular risk factors is unknown. We examined the effects of exercise on
      coplanar PCB-induced cardiovascular risk factors including oxidative stress,
      inflammation, impaired glucose tolerance, hypercholesteremia, and endothelium
      dependent relaxation. Male ApoE(-/-) mice were divided into sedentary and
      exercise groups (voluntary wheel running) over a 12-week period. Half of each
      group was exposed to vehicle or PCB 77 at weeks 1, 2, 9, and 10. For ex vivo
      studies, male C57BL/6 mice exercised via voluntary wheel training for 5 weeks and
      then were administered with vehicle or PCB 77 24 h before vascular reactivity
      studies were performed. Exposure to coplanar PCB increased risk factors
      associated with cardiovascular disease, including oxidative stress and systemic
      inflammation, glucose intolerance, and hypercholesteremia. The 12-week exercise
      intervention significantly reduced these proatherogenic parameters. Exercise also
      upregulated antioxidant enzymes including phase II detoxification enzymes.
      Sedentary animals exposed to PCB 77 exhibited endothelial dysfunction as
      demonstrated by significant impairment of endothelium-dependent relaxation, which
      was prevented by exercise. Lifestyle modifications such as aerobic exercise could
      be utilized as a therapeutic approach for the prevention of adverse
      cardiovascular health effects induced by environmental pollutants such as PCBs.

PMID- 25586618
TI  - Dynamics of dissolved organic matter during four storm events in two forest
      streams: source, export, and implications for harmful disinfection byproduct
      formation.
AB  - Dynamics of river dissolved organic matter (DOM) during storm events have
      profound influences on the downstream aquatic ecosystem and drinking water
      safety. This study investigated temporal variations in DOM during four storm
      events in two forest headwater streams (the EH and JH brooks, South Korea) and
      the impacts on the disinfection byproducts (DBPs) formation potential. The within
      event variations of most DOM quantity parameters were similar to the flow rate in
      the EH but not in the larger JH brook. The dissolved organic carbon (DOC) showed
      clockwise and counterclockwise hysteresis with the flow rate in the EH and JH
      brooks, respectively, indicating the importance of both flow path and DOM source
      pool size in determining the effects of storm events. The stream DOM became less
      aromatic/humified from the first to the last event in both brooks, probably due
      to the increasing fresh plant pool and the decreasing leaf litter pool during the
      course of rainy season. The DOC export during each event increased 1.3-2.7- and
      1.1-7.0-fold by stormflows in the EH and JH brooks, respectively. The leaf litter
      and soil together was the major DOM source, particularly during early events. The
      enhanced DOM export probably increases the risks of DBPs formation in
      disinfection, as indicated by a strong correlation observed between DOC and
      trihalomethanes formation potential (THMFP). High correlations between two humic
      like fluorescent components and THMFP further suggested the potential of
      assessing THMFP with in situ fluorescence sensors during storms.

PMID- 25586617
TI  - Cadmium-induced rhizospheric pH dynamics modulated nutrient acquisition and
      physiological attributes of maize (Zea mays L.).
AB  - Cadmium (Cd) is a highly mobile toxic element in soil-plant systems that
      interferes with plant growth and nutrient acquisition by modulations in the
      rhizospheric environment. The current study investigated the influence of maize
      roots on the medium pH, alterations in nutrient uptake, and impact on the plant's
      physiological attributes under Cd stress. Among the nine maize cultivars,
      subjected to Cd stress (9.15 mg/kg of sand), one was identified as Cd tolerant
      (3062-Pioneer) and the second as Cd sensitive (31P41-Pioneer). The selected maize
      cultivars were grown in nutrient solutions supplemented with 0, 10, 20, 30, 40,
      or 50 MUM CdCl2 under controlled conditions and a starting pH of 6.0. The
      rhizospheric pH dynamics were monitored each day up to 3 days. Both cultivars
      caused medium basification; however, the response was different at low (10 and 20
      MUM) Cd treatments (sensitive cultivar caused medium basification) and at higher
      (50 MUM) Cd treatment (tolerant cultivar caused medium basification).
      Furthermore, higher Cd was accumulated by the sensitive cultivar which was
      predominantly found in the roots. Higher Cd levels in the medium resulted in
      increased uptake and translocation of both Cd and K (in the tolerant cultivar) or
      only Cd (in the sensitive cultivar). Uptake of other nutrients (Ca, Zn, and Fe)
      was antagonistically affected by Cd stress in both cultivars. Moreover, Cd stress
      significantly impaired chlorophyll content, catalase activity, and total protein
      content; irrespective of the genotype. The malondialdehyde (MDA) content was
      found to increase, in both cultivars, together with Cd level. However, the extent
      to which Cd interfered with the studied attributes was more pronounced in the
      sensitive cultivar as compared to the tolerant one. It is concluded that the
      maize roots responded to Cd stress by initiating modulations of medium pH which
      might be dependent on Cd tolerance levels. The study results may help to develop
      strategies to reduce Cd accumulation in maize and decontamination of metal
      polluted soil sediments.

PMID- 25586619
TI  - Photolysis degradation of polyaromatic hydrocarbons (PAHs) on surface sandy soil.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are potent environmental pollutants, and
      some of them have been identified as carcinogenic and mutagenic. To advance the
      knowledge of the environmental fate of PAHs, we systematically investigated the
      influence of different UV wavelengths irradiation on photolysis of PAHs on sandy
      soil under tow wavelengths (254 and 306 nm) UV irradiation for six PAHs. In
      addition, kinetic model and influence of several parameters on PAHs photolysis
      have been studied. The results obtained indicated that UV radiation with a
      wavelength of 306 nm was more efficient in the photolysis of the polycyclic
      aromatic hydrocarbons. Our results showed that fluoranthene (Flt) was the fastest
      in decomposition, has the greatest value for the coefficient of photolysis (7.4 *
      10(-3) h(-1)), and has less half-life, reaching 94 h when using a wavelength of
      254 nm. The results indicated that the pyrene (Pyr) was more resistant to
      photolysis in comparison with indeno(1,2,3-cd) pyrene (IP) and fluoranthene
      (Flt). The results indicate that photolysis is a successful way to remediate the
      six studied PAHs compounds. 

PMID- 25586620
TI  - Influence of dietary zinc and copper on apparent mineral retention and serum
      biochemical indicators in young male mink (Mustela vison).
AB  - An experiment was conducted in a 3 * 3 (Cu * Zn) factorial experiment based on a
      completely randomized design to evaluate the effects of dietary copper and zinc
      on apparent mineral retention and serum biochemical indicators in young male mink
      on a corn-fish meal based diet. Animals were fed basal diets supplemented with Cu
      from copper sulfate (CuSO4) and Zn from zinc sulfate (ZnSO4). Supplemental Cu
      levels were 0, 15, and 30 mg/kg copper, respectively, while supplemental Zn
      levels were 0, 150, and 300 mg/kg, respectively. A metabolism trial of 4 days was
      conducted during the last week of experimental feeding. Blood samples were
      collected via the toe clip to determine blood hematology and blood metabolites.
      Copper excretion, retention, and digestibility were influenced by dietary copper
      (P < 0.05), however, there was also a zinc-copper interaction. Copper
      digestibility and retention were substantially reduced when zinc was added to the
      low copper diet but showed little change with zinc supplementation of the high
      copper diet. Both plasma Cu and plasma Zn were influenced by dietary level of the
      respective mineral (P < 0.05). There was no influence of dietary copper on plasma
      zinc; however, high Zn in the diet reduced plasma Cu concentrations. There was a
      zinc-copper interaction for plasma Cu (P = 0.053). Cu-Zn superoxide dismutase (Cu
      Zn SOD) activity tended to be influenced by dietary zinc (P = 0.065) and dietary
      copper (P = 0.035). Dietary copper had a significant effect on ceruloplasmin
      (CER) and triglyceride (TG) concentrations (P < 0.05). Our results show that
      moderately high Zn in the diet (Zn:Cu ratio of 40:1) significantly reduce the
      apparent Cu digestibility. Our results also show that moderately high Cu in the
      diet increases Cu retention, but not reduces Zn absorption, and moderately high
      Zn in the diet reduced plasma Cu concentrations and CER activity.

PMID- 25586621
TI  - Efficacy of selenium from hydroponically produced selenium-enriched kale sprout
      (Brassica oleracea var. alboglabra L.) in broilers.
AB  - An experiment was conducted to determine the efficacy of Se from hydroponically
      produced Se-enriched kale sprout (HPSeKS) on performance, carcass
      characteristics, tissue Se concentration, and physiological responses of broilers
      in comparison to that of Se from Se-enriched yeast and sodium selenite. Three
      hundred and sixty male broilers, 10 days of age, were assigned to 6 groups, 4
      replicates of 15 broilers each, according to the completely randomized design.
      The dietary treatments were the following: T1: control diet; T2: control diet
      plus 0.3 mg Se/kg from sodium selenite; T3: control diet plus 0.3 mg Se/kg from
      Se-enriched yeast; and T4, T5, and T6: control diet plus 0.3, 1.0, and 2.0 mg
      Se/kg from HPSeKS, respectively. The results found that dietary Se
      supplementation did not (p > 0.05) alter performance and carcass characteristics
      of broilers. Se supplementation increased (p < 0.05) Se concentrations in the
      liver and kidney of broilers. Heart tissue Se concentration of broilers fed Se
      from sodium selenite was lower (p < 0.05) than that of broilers fed Se from
      HPSeKS and Se-enriched yeast. Selenium from HPSeKS increased higher (p < 0.05)
      GSH-Px activity when compared to Se from sodium selenite and Se-enriched yeast.
      The results indicated that the efficacy of Se from HPSeKS was comparable in
      increasing tissue Se concentration, but higher in improving GSH-Px activity in
      Rbc when compared to those of Se from Se-enriched yeast.

PMID- 25586622
TI  - Zinc might prevent heat-induced hepatic injury by activating the Nrf2-antioxidant
      in mice.
AB  - Zinc (Zn) is generally known to be an essential trace element with growth
      promoting and antioxidant activities. The present study was performed to clarify
      the role of Zn in the livers of heat-treated mice. Eight-week-old male mice were
      divided into control (Con), heat treatment (HT) and heat treatment plus zinc
      groups (HT + Zn) and were fed diets containing 60, 60, or 300 mg/kg Zn (zinc
      sulfate), respectively. After 30 days of feeding on their respective diets, the
      control group was maintained at a controlled temperature (25  degrees C), whereas
      the HT and HT + Zn groups were exposed to an elevated ambient temperature (40-42 
      degrees C) for 2 h each day. After heat exposure for seven consecutive days, sera
      and liver tissues were collected. The mice in the HT group exhibited reduced
      liver weights and lower hepatosomatic indices. Histological findings revealed
      that the hepatocytes of the HT group were subjected to serious damage and
      exhibited irregular arrangements and nuclear pyknosis. Moreover, in the HT group,
      the hepatic malondialdehyde levels were significantly increased, while the serum
      alkaline phosphatase levels, hepatic copper/zinc-superoxide dismutase (CuZn-SOD)
      and glutathione peroxidase activities were significantly reduced compared to
      those of the control group. However, in the HT + Zn group, the histomorphology of
      the liver was restored, the serum aspartate aminotransferase (AST) level was
      significantly decreased, and the hepatic CuZn-SOD activity was significantly
      increased compared to the HT group. Furthermore, expressions of the hepatic Nrf2
      protein and Nrf2, Keap1, and NQO1 genes in the HT + Zn group were not only higher
      than the HT group but also higher than the control group. Zn might alleviate heat
      induced hepatic injury as revealed by restored histomorphology and AST level. Our
      results further suggest that Zn might exert its protective effects via the
      activation of the Nrf2-antioxidant pathway.

PMID- 25586623
TI  - Evaluation of lactate detection using selective multiple quantum coherence in
      phantoms and brain tumours.
AB  - Lactate is a product of glucose metabolism. In tumour tissues, which exhibit
      enhanced glycolytic metabolism, lactate signals may be elevated, making lactate a
      potential useful tumour biomarker. Methods of lactate quantitation are
      complicated because of overlap between the lactate methyl doublet CH3 resonance
      and a lipid resonance at 1.3 ppm. This study presents the use of a selective
      homonuclear multiple quantum coherence transfer sequence (SelMQC-CSI), at 1.5 T,
      to better quantify lactate in the presence of lipids. Work performed on phantoms
      showed good lactate detection (49%) and lipid suppression (98%) efficiencies. To
      evaluate the method in the brain, the sequence was tested on a group of 23
      patients with treated brain tumours, either glioma (N=20) or secondary metastases
      in the brain (N=3). Here it was proved to be of use in determining lactate
      concentrations in vivo. Lactate was clearly seen in SelMQC spectra of glioma,
      even in the presence of lipids, with high grade glioma (7.3 +/- 1.9 mM, mean +/-
      standard deviation) having higher concentrations than low grade glioma (1.9 +/-
      1.5 mM, p=0.048). Lactate was not seen in secondary metastases in the brain.
      SelMQC-CSI is shown to be a useful technique for measuring lactate in tumours
      whose signals are otherwise contaminated by lipid.

PMID- 25586624
TI  - Long-term symptomatic relief of bullous keratopathy with amniotic membrane
      transplant.
AB  - The purpose of this study was to assess the long-term outcome of patients with
      symptomatic bullous keratopathy after amniotic membrane transplant. A
      retrospective cohort study includes that 20 patients with symptomatic bullous
      keratopathy, who have underwent amniotic membrane transplant at the Department of
      Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Prince of
      Wales Hospital & Alice Ho Miu Ling Hospital, Hong Kong between 04/1998 and
      06/2011, were invited back. Clinical examination was performed, including, pain
      score assessment (pain score out of 10), epithelial healing, and vision. A total
      of 21 eyes of 20 patients returned for our study. The majority of eyes
      experienced pain reduction (94 %), with a significant mean pain score difference
      of 6.8 +/- 2.6, 2-tail p < 0.001 (99 % CI 4.9-8.7). The mean pre-operative and
      post-operative pain scores were 7.3 +/- 2.9 and 0.5 +/- 1.0, respectively. 16
      eyes (76 %) were completely pain free, and 10 eyes (47 %) remained symptom free
      after a mean follow-up of 39.0 +/- 36.3 months (range 5-171 months). The median
      epithelial healing time was 2 weeks (range 1-20 weeks). Amniotic membrane
      transplant may be considered as a longer-term treatment for bullous keratopathy
      patients, especially in patients with poorer visual prognosis, but it may also be
      used as an interim measure for patients awaiting corneal transplant.

PMID- 25586625
TI  - Relapsing acute lymphoblastic leukemia presenting with a rapidly enlarging and
      vision-threatening orbital mass.
AB  - This case report describes a patient with known acute lymphoblastic leukemia
      (ALL) presenting with a rapidly enlarging and vision-threatening orbital mass.
      Orbital disease is rare in patients with ALL, and to our knowledge only six cases
      have been previously described, five of which are in children. We describe a 36
      year-old Caucasian female with known acute lymphoblastic leukemia who developed
      markedly decreased visual acuity, proptosis, and elevated intraocular pressure
      over the course of 12 h. She was treated with emergent surgical intervention
      followed by intrathecal chemotherapy and intravenous steroids. Following medical
      and surgical intervention, the patient demonstrated rapid resolution of symptoms
      and a return to baseline visual acuity. The initial presentation of acute onset
      proptosis with optic nerve compromise can be suggestive of infectious etiologies,
      however, this case suggests caution in evaluation of patients with known systemic
      malignancy, particularly ALL, as early intervention with systemic steroids and
      surgery may result in return of visual function. 

PMID- 25586626
TI  - Pulmonary function and blood gases after gastric bypass and lifestyle
      intervention: a comparative study.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Impaired lung function associated with
      obesity improves with weight loss. WHAT THIS STUDY ADDS: This is the first study
      to compare the effects of obesity surgery and intensive lifestyle intervention on
      pulmonary function and arterial blood gases. Arterial oxygenation and pulmonary
      function improved to a greater extent after gastric bypass than after lifestyle
      intervention. The superiority of surgical treatment might be mediated by greater
      weight loss after gastric bypass. Impaired lung function associated with obesity
      improves with weight loss. The effects of obesity surgery and intensive lifestyle
      intervention on pulmonary function and arterial blood gases have not previously
      been subjected to comparative examination. In this 1-year non-randomized
      controlled clinical trial (ClinicalTrials.gov identifier NCT00273104), 139
      morbidly obese subjects (19-66 years, mean [standard deviation] body mass index
      [BMI] 45.1 kg m(-2) [5.6], 107 women) were treated with either Roux-en-Y gastric
      bypass surgery (n = 76) or intensive lifestyle intervention (n = 63). Mean weight
      reduction was 30 (8)% and 8 (9)%, respectively. Dynamic and static lung volumes,
      gas diffusing capacity and arterial blood gases were measured. Compared with
      lifestyle intervention, surgery resulted in a significantly greater increase in
      forced vital capacity (mean [95% confidence interval] between-group difference, 7
      [4-10]%), forced expiratory volume in 1 s (7 [5-9]%), total lung capacity (5 [1
      8]%), vital capacity (7 [4-9]%), functional residual capacity (18 [12-24]%),
      expiratory reserve volume (48 [30-66]%) and partial pressure of oxygen in
      arterial blood (0.5 [0.0-1.0] kPa). These associations either disappeared or
      diminished after adjusting for weight loss. Reduced central adiposity (waist
      circumference and waist-to-hip ratio) and systemic inflammation (C-reactive
      protein and adiponectin) had no effect on pulmonary function beyond the effect of
      reduced general adiposity (BMI). In morbidly obese subjects, gastric bypass
      surgery is more effective than lifestyle intervention at improving arterial
      oxygenation and pulmonary function. The effect might be mediated by greater
      weight loss after surgical treatment.

PMID- 25586627
TI  - Self-reported symptoms of adult attention deficit hyperactivity disorder among
      obese patients seeking bariatric surgery and its relation to alcohol consumption,
      disordered eating and gender.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Symptoms of adult attention deficit
      hyperactivity disorder (ADHD) are common among people with obesity. Symptoms of
      ADHD are associated with other impulsive behaviours. Impulsivity can manifest
      differently in women and men. WHAT THIS STUDY ADDS: The prevalence of ADHD
      symptoms was equal in both sexes in this patient group. ADHD symptoms were
      associated with hazardous alcohol consumption in men but not in women. It may be
      important to investigate several comorbid conditions simultaneously instead of a
      single diagnosis. Eating disorders and adult attention deficit hyperactivity
      disorder (ADHD), both characterized by deficits in impulse control, are common
      among bariatric surgery patients. Previous studies in other groups have found
      gender differences in how symptoms of ADHD and eating disorders manifest as women
      show more disordered eating and men show more risk consumption of alcohol. In the
      present study, the association between symptoms of adult ADHD, eating disorders
      and hazardous alcohol consumption was investigated, while considering gender
      differences. Self-report questionnaires were obtained from 276 bariatric surgery
      patients 3-6 months before surgery. The prevalence rates of adult ADHD and binge
      eating disorder (BED) were 8.6% and 6.3%, respectively, with no evidence of
      gender difference in the prevalence rates. Hazardous alcohol consumption was
      reported by a significantly larger portion of men (16.9%) than women (8.6%).
      There was an association between adult ADHD and both BED and hazardous alcohol
      consumption. However, symptoms of adult ADHD were associated with hazardous
      alcohol consumption in men but not in women. Our results suggest gender
      differences in hazardous alcohol consumption and self-reported symptoms of
      disordered eating despite similar prevalence rate of BED, but no gender
      difference in symptoms of adult ADHD. Finally, as the associations between these
      variables seem to be different in women and men, future studies need to
      investigate potential gender-specific functional and temporal relations between
      these variables.

PMID- 25586628
TI  - Relationships between total and regional adiposity and epicardial fat in obese
      women: how can dual-energy X-ray absorptiometry be associated with
      echocardiographic epicardial fat measurements?
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Obesity is an increasingly prevalent
      metabolic disorder and it is associated with a large number of comorbidities,
      including cardiovascular diseases. Adipose tissue is an active endocrine organ
      and its ectopic depots and distribution have different metabolic meanings on
      risks for health; as a matter of fact, epicardial fat seems to play a specific
      role in cardiovascular diseases. The use of dual-energy X-ray absorptiometry
      (DXA) to evaluate and follow-up patients affected by obesity is becoming a very
      important point in the management of the disease. WHAT THIS STUDY ADDS: An
      investigation of the association between epicardial fat and regional adiposity by
      DXA in female obese patients. The total amount of central (trunk) fat mass is
      more strongly correlated than android visceral fat mass to epicardial thickness
      in obese women. In the interpretation of whole-body DXA data, physician should
      consider trunk fat mass for good and independent predictivity on epicardial fat
      depots. Our aim was to analyse in a population of obese women the relationship
      between the amount of epicardial fat as measured by transthoracic
      echocardiography (US) and the parameters of regional adiposity by dual-energy X
      ray absorptiometry (DXA), with particular reference to a new software for
      visceral fat assessment and to a new 'heart-suited' regions of interests (ROIs).
      Sixty patients who satisfied technical inclusion criteria underwent whole-body
      DXA scan and US on the same day. Total and android fat mass (FM) and FM
      percentage (FM%) were considered as well as visceral fat (VAT) subcompartment in
      the android region; moreover, six new ROIs were designed on whole-body DXA images
      for the investigation of adiposity parameters at heart level. US provided
      epicardial fat thickness (EPI-thickness) and area (EPI-area), as measured
      following previously validated methods. Body mass index (BMI), gynoid and lower
      limbs (FM and FM%) were found not statistically correlated with EPI-thickness.
      The highest correlation was achieved by trunk FM (and FM%, with r = 0.544 and
      0.480 respectively, P < 0.001), followed by ROI-1 FM (ROI-1 was drawn following
      thoroughly the cardiac profile), and android FM. Multivariate analysis including
      age, weight, BMI, trunk FM and the new ROIs (added one by one), retained in the
      final model trunk FM. Correlations of DXA with EPI-area were superimposable. In
      obese women, VAT or other new-designed ROIs are not better correlated than
      traditional ROIs (i.e. trunk) with epicardial fat amount.

PMID- 25586629
TI  - Behaviours associated with weight loss maintenance and regaining in a
      Mediterranean population sample. A qualitative study.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: In the US, the National Weight Control
      Registry revealed lifestyle behaviours shared by weight loss maintainers. In the
      US and the UK, qualitative studies compared the experiences of weight loss
      maintainers and regainers. High rates of physical activity, a low-energy/low-fat
      diet, weight self-monitoring, breakfast consumption and flexible control of
      eating are well-established maintenance behaviours. WHAT THIS STUDY ADDS: The
      Mediterranean lifestyle has not been studied relative to weight loss maintenance.
      This study focused on a sample of Greek maintainers and regainers. Maintainers
      emphasized home-cooked meals; their diet does not appear to be low-fat, as home
      cooked Greek meals are rich in olive oil. Having a small dinner is a common
      strategy among maintainers. Health motives were not mentioned by maintainers.
      Maintainers, but not regainers, appeared to compensate for emotional eating.
      Weight loss maintenance is imperative to successful obesity treatment. We
      qualitatively explored lifestyle behaviours associated with weight regulation, in
      a sample of Greek volunteers who had lost weight and either maintained or
      regained it. A 10% intentional loss maintained for at least one year was
      considered successful maintenance. Volunteers (n = 44, 41% men) formed eight
      focus groups, four of maintainers and four of regainers. Questions regarded
      weight loss, weight maintenance or regaining, and beliefs on weight maintenance
      and regaining. All discussions were tape recorded. Maintainers lost weight on
      their own, whereas regainers sought professional help. Maintainers exercised
      during both the loss and maintenance phases, whereas regainers showed
      inconsistent physical activity levels. Health motives for weight loss were
      mentioned only by regainers. Emotional eating was a common barrier, but only
      maintainers compensated for it. Maintainers continuously applied specific
      strategies to maintain their weight: emphasizing home-cooked meals, high eating
      frequency, a small dinner, portion size regulation, and sweets' intake
      regulation. Regainers considered the behaviours leading to weight loss different
      from their normal lifestyle, and resumed their old habits when the diet was over.
      However, both groups believed that for long-term success, lifestyle changes need
      to be permanent.

PMID- 25586630
TI  - Weight loss for individuals with type 2 diabetes following a very-low-calorie
      diet in a community-based setting with trained facilitators for 12 weeks.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Approximately 80% of people with type 2
      diabetes mellitus (T2DM) are overweight or obese. Weight loss produces numerous
      benefits in T2DM. People with T2DM have difficulty losing and maintaining weight.
      WHAT THIS STUDY ADDS: Provision of a very-low-calorie diet (VLCD) with group
      support and behaviour therapy for patients with T2DM is feasible within a
      community-based setting with trained facilitators. VLCD approaches for weight
      management in T2DM can achieve more than 90% of weight loss as compared with
      obese individuals without T2DM. Identification of the need to investigate the
      full impact of this approach in patients with T2DM by assessing changes in
      glycaemia, liver function and medication. Approximately 80% of people with type 2
      diabetes mellitus (T2DM) are overweight or obese, and obesity compounds the
      cardiovascular risk of T2DM. The aim of this retrospective study was twofold:
      first, to investigate whether a 12-week community-based very-low-calorie diet
      (VLCD) programme can result in important weight loss; and second, to investigate
      any potential difference in the weight loss achieved using this community-based
      approach in individuals with and without T2DM. Three hundred and fifty-five
      participants with T2DM were matched for age, body mass index (BMI) and gender to
      participants without T2DM (total cohort comprised 204 males: 506 females (mean +/
      standard deviation); age (years) 54.0 +/- 9.1; BMI (kg m(-2) ) 41.6 +/- 8.1;
      weight (kg) 116.1 +/- 25.1). The programme included a daily intake of 550 kcal in
      addition to group support and behaviour therapy provided by trained facilitators
      within a community-based setting. After 12 weeks, there was significant weight
      loss within each group when compared with baseline (T2DM: 115.0 +/- 24.4 kg vs.
      96.7 +/- 21.4 kg, P < 0.0001; non-T2DM: 117.2 +/- 25.8 kg vs. 97.3 +/- 22.2 kg, P
      < 0.0001). At 12 weeks, weight change (-18.3 +/- 7.3 kg vs. -19.9 +/- 7.0 kg, P =
      0.012) and BMI change (-6.7 +/- 2.9 kg m(-2) vs. -7.1 +/- 2.1 kg m(-2) , P =
      0.011) were significantly less in the T2DM group when compared with the non-T2DM
      group. Our results suggest that the use of VLCD approaches for weight management
      in T2DM can achieve more than 90% of the weight loss seen in obese individuals
      without T2DM.

PMID- 25586631
TI  - Connecting tube colonic erosion and gastrocolic fistula formation following late
      gastric band erosion.
AB  - Band erosion is a rare complication of laparoscopic adjustable gastric banding
      (LAGB) with a reported prevalence varying from 0.3% to 14%. Intraluminal colonic
      erosion of the connecting tube is very rare, as only isolated cases have been
      described. Consequently, simultaneous gastric band erosion and connecting tube
      colonic erosion is an extremely rare event. Herein, we present a case of a woman
      with morbid obesity, who submitted to LABG 4 years ago. The patient presented
      with symptoms and signs of right lower quadrant peritonitis. Computed tomography
      (CT) demonstrated migration of the band into the gastric lumen, inflammation
      around the intra-abdominal course of the connecting tube and an inflammatory mass
      surrounding the tube at the right lower quadrant. Laparotomy revealed the eroded
      band, the eroded transverse colon from the connecting tube, a gastrocolic fistula
      along the course of the tube and a right lower quadrant phlegmon. The connecting
      tube was mobilized from the surrounding adherent tissues, the gastric band
      removed, the stomach and colon walls closed, and the gastrocolic fistula excised.
      To our knowledge this is the second case of concurrent band erosion and
      connecting tube colonic erosion along with gastrocolic fistula formation in a
      patient with morbid obesity treated with LAGB. 

PMID- 25586633
TI  - Surgical cutdown versus percutaneous access in transfemoral transcatheter aortic
      valve implantation: Insights from the Brazilian TAVI registry.
AB  - OBJECTIVE: To compare the 1-year outcomes of complete percutaneous approach
      versus surgical vascular approach for transfemoral transcatheter aortic valve
      implantation (TAVI), among "real-world" patients from the multi-center Brazilian
      TAVI registry. BACKGROUND: Vascular access still remains a major challenge for
      TAVI via transfemoral approach. Vascular access through complete percutaneous
      approaches or through open surgical vascular techniques seems to be acutely
      similar. However, the long-term outcomes of both techniques remain poorly
      described. METHODS: The study population comprised all patients treated via
      transfemoral route in the Brazilian TAVI registry, a "real-world", nation-based,
      multi-center study. Patients were divided according to the initial vascular
      access approach (percutaneous vs. surgical) and clinically followed-up for 1
      year. The primary endpoint was the incidence of combined adverse events all-cause
      mortality, life-threatening bleeding, and/or major vascular complication at 1
      year. RESULTS: A total of 402 patients from 18 centers comprised the study
      population (percutaneous approach in 182 patients; surgical cutdown approach 220
      patients). The incidence of combined adverse events was not different in the
      percutaneous and the surgical groups at 30 days (17.6% vs. 16.3%; P = 0.8) and at
      1 year (primary endpoint) (30.9% vs. 28.8%; P = 0.8). Also, the study groups
      overall were comparable regarding the incidence of each individual safety adverse
      events at 30 days and at 1 year. CONCLUSION: Total percutaneous techniques or
      surgical cutdown and closure may provide similar safety and effectiveness during
      the first year of follow-up in patients undergoing transfemoral TAVI.

PMID- 25586635
TI  - Microarray technology to investigate genes associated with papillary thyroid
      carcinoma.
AB  - DNA microarray data on thyroid tissue from patients with papillary thyroid
      carcinoma (PTC) and from healthy controls were compared in order to investigate
      the regulatory genes and uncover the underlying regulatory network in PTC. The
      DNA microarray data set, GSE3678, was downloaded from Gene Expression Omnibus
      database. This included seven thyroid tissue samples from patients with PTC and
      seven samples from healthy controls. Raw data were processed and differentially
      expressed genes (DEGs) were identified using corresponding R packages. Gene
      regulation analysis was conducted using TRANSFAC(r) and TRED. A total of 171 DEGs
      were obtained. A regulatory network was then established, using 104 of the DEGs.
      Subsequently, pathway enrichment analyses of the genes were conducted using
      Database for Annotation, Visualization and Integrated Discovery (DAVID) online
      tool. Three differentially expressed transcription factors were identified:
      Trefoil factor 3, cut-like homeobox 2 and forkhead box protein A2. The most
      significant pathways involving the 104 DEGs were pathways involved in cancer.
      Biological process analysis using DAVID, suggested that these genes were
      associated with the positive regulation of gene expression, gene transcription
      and metabolic processes. The present study identified a range of genes associated
      with the development of PTC. The results of the present study were beneficial for
      understanding the regulatory mechanisms involved in PTC, and for developing
      clinical diagnostic and therapeutic approaches for this disease.

PMID- 25586634
TI  - Blockade of the GLT-1 Transporter in the Central Nucleus of the Amygdala Induces
      both Anxiety and Depressive-Like Symptoms.
AB  - Depression has been associated with abnormalities in glutamatergic
      neurotransmission and decreased astrocyte number in limbic areas. We previously
      demonstrated that global and prefrontal cortical blockade of the astrocytic
      glutamate transporter (GLT-1) induces anhedonia and c-Fos expression in areas
      that regulate anxiety, including the central amygdala (CEA). Given the role of
      the amygdala in anxiety and the high degree of comorbidity between anxiety and
      depression, we hypothesized that GLT-1 blockade in the CEA would induce symptoms
      of anhedonia and anxiety in rats. We microinjected the GLT-1 inhibitor,
      dihydrokainic acid (DHK), into the CEA and examined effects on intracranial self
      stimulation (ICSS) as an index of hedonic state, and on behavior in two anxiety
      paradigms, elevated plus maze (EPM) and fear conditioning. At lower doses, intra
      CEA DHK produced modest increases in ICSS responding (T0). Higher doses resulted
      in complete cessation of responding for 15 min, suggesting an anhedonic or
      depressive-like effect. Intra-CEA DHK also increased anxiety-like behavior such
      that percent time in the open arms and total entries were decreased in the EPM
      and acquisition of freezing behavior to the tone was increased in a fear
      conditioning paradigm. These effects did not appear to be explained by non
      specific changes in activity, because effects on fear conditioning were assessed
      in a drug-free state, and a separate activity test showed no significant effects
      of intra-CEA DHK on locomotion. Taken together, these studies suggest that
      blockade of GLT-1 in the CEA is sufficient to induce both anhedonia and anxiety
      and therefore that a lack of glutamate uptake resulting from glial deficits may
      contribute to the comorbidity of depression and anxiety. 

PMID- 25586636
TI  - Dietary anthocyanins as a complementary medicinal approach for management of
      inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is thought to result from a chronic or relapsing
      activation of the immune system in the GI tract. A growing body of evidence
      confirms the health benefits of dietary anthocyanins as plant-derived natural
      agents. The aim of this review is to provide an overview of several natural
      products rich in anthocyanins used worldwide for the treatment of IBD.
      Anthocyanins possess both protective and therapeutic functions in the management
      of IBD by alleviating oxidative stress processes, cytoprotective functions,
      downregulation of inflammatory cytokines and suppressing cellular signaling
      pathways of inflammatory processes. In conclusion, the consumption of anthocyanin
      rich natural formulations must be promoted on the basis of their possible
      function in the prevention and treatment of gastrointestinal inflammatory
      disorders. 

PMID- 25586637
TI  - Heat stroke: typical MRI and (1)H-MRS features.
AB  - Heat stroke (HS) is a life-threatening condition characterized by severe
      hyperthermia associated with central nervous system abnormalities. We present two
      interesting cases of HS with symmetric lesions in the dentate nuclei and
      cerebellar peduncles. Typical MRI and (1)H-MRS features including follow-up
      studies are illustrated. 

PMID- 25586638
TI  - Sex-sorted canine sperm cryopreservation: limits and procedural considerations.
AB  - The aim of this study was to define a protocol to store dog sperm before and
      after sorting to obtain an insemination dose sufficient to allow the conception
      by artificial insemination. Experiment 1 and 2 were performed to evaluate the
      more appropriate extender for preserving at room temperature dog sperm before and
      after sorting. Four extenders were tested: (1) Tris-fructose-citrate (TFC), (2)
      Tris-glucose-citrate (TGC), (3) modified Tyrode's albumin lactate pyruvate medium
      (mTALP), and (4) third fraction of the ejaculate (after centrifugation at 5000* g
      for 10 minutes; III FRAC). Experiment 3 and 4 were performed to evaluate the
      ability of dog semen to withstand sex sorting and freezing/thawing. Modified
      Tyrode's albumin lactate pyruvate medium was the best extender for canine sperm
      storage at room temperature (20  degrees C-25  degrees C) before (total motility:
      TFC, 8.3 +/- 1.7; TGC, 50.0 +/- 11.5; mTALP, 70.0 +/- 0.1; III FRAC, 25.0 +/- 1
      0.4; P < 0.05) and after sorting (total motility: TFC, 7.3 +/- 1.5; TGC, 10.3 +/-
      1.5; mTALP, 33.3 +/- 6.7; III FRAC, 8.7 +/- 5.8; P < 0.05), even if at 24-hour
      sorted sperm quality was impaired in all extenders tested herein. Sperm quality
      decreased after sorting (total motility: control, 92.5 +/- 0.9; sorted, 52.9 +/-
      6.0; P < 0.05) and, especially, after freezing/thawing (total motility: frozen
      control, 25.7 +/- 4.1; frozen sorted, 2.4 +/- 1.2; P < 0.05). In conclusion,
      mTALP is an appropriate medium for canine sperm storage before and soon after
      sorting (hours), but a long storage period of sexed sperm at room temperature is
      not adequate. Cryopreservation greatly impaired sperm quality, and further
      studies are needed to optimize the freezing protocol for sexed dog sperm.

PMID- 25586639
TI  - Production of lion (Panthera leo) blastocysts after in vitro maturation of
      oocytes and intracytoplasmic sperm injection.
AB  - Assisted reproductive techniques are becoming widely applied to the breeding of
      endangered species, but establishing reliable protocols for the production of
      embryos in vitro is challenging because of the scarcity of sample material. In
      our study, we applied an assisted reproductive technique protocol for IVM and
      intracytoplasmic sperm injection (ICSI), developed in the domestic cat, to
      oocytes retrieved from ovaries of four 2-year-old lionesses (Panthera leo) eight
      hours postmortem. In total, 68 cumulus-oocyte complexes of good quality were
      randomly distributed and cultured for 32 to 34 hours in two different maturation
      culture media, consisting of Medium 199 with Earle's salts, 3 mg/mL BSA, 0.1
      mg/mL cysteine, 1.4 mg/mL sodium pyruvate, 0.6 mg/mL sodium lactate, 0.15 mg/mL l
      glutamine, and 0.055 mg/mL gentamicin. Hormonal supplementation of IVM_1 was 0.02
      IU/mL FSH and 0.05 IU/mL LH; IVM_2 consisted of 1.64 IU/mL FSH, 1.06 IU/mL LH,
      and 1 MUg/mL 17beta-estradiol. Differences in hormonal supplementation did not
      produce significant differences in oocyte maturation rates, which were 39.4% in
      IVM_1 and 34.3% in IVM_2. Matured oocytes were microinjected with homologous
      frozen-thawed spermatozoa, and subsequent cleavage rates were 30.8% and 58.3%,
      respectively. Half of the embryos derived from oocytes matured in IVM_1 developed
      into blastocysts, whereas only 28.6% of embryos from oocytes matured in IVM_2
      reached the blastocyst stage. Morula stages were present from Day 6 onward, and
      blastocyst stages from Day 9 on, indicating a slower developmental speed in
      comparison with domestic cats. This is the first report of in vitro-produced
      blastocysts using ICSI in the lion, and the results report that IVM and ICSI can
      be successfully performed with cumulus-oocyte complexes retrieved from ovaries
      after eight hours of shipping, obtaining competent embryos in culture. 

PMID- 25586640
TI  - An in vitro investigation of the actions of reproductive hormones on the cervix
      of the ewe in the follicular stage: the effects of 17beta-estradiol, oxytocin,
      FSH, and arachidonic acid on the cervical pathway for the synthesis of
      prostaglandin E2.
AB  - During the periovulatory period, the cervix of the ewe relaxes and this mechanism
      is thought to be mediated by oxytocin and prostaglandin E2 (PGE2) in response to
      increased concentrations of 17beta-estradiol and perhaps FSH. The aim of the
      study was to determine the in vitro effects of 17beta-estradiol, FSH, oxytocin,
      and arachidonic acid (AA) on the synthesis of PGE2 and on the expression of
      oxytocin receptor (OTR), cytoplasmic phospholipase A2 (cPLA2), and cyclooxygenase
      2 (COX-2) in explants of cervical tissue collected from ewes in the periovulatory
      phase of the estrous cycle. Cervical minces from ewes in the follicular phase of
      the estrous cycle were cultured in supplemented Eagle's Minimum Essential Medium
      for 48 hours with 17beta-estradiol, FSH, oxytocin, or AA. After incubation, the
      tissue was stored at -80  degrees C and the media at -20  degrees C. Western
      immunoblotting was used to determine relative levels of OTR, cPLA2, and COX-2 in
      cervical tissue, and the media was analyzed by RIA, to determine the
      concentration of PGE2. The addition of 17beta-estradiol increased the
      concentration of PGE2 in the media (P = 0.001), the levels of COX-2 (P = 0.02)
      and OTR (P = 0.006) but not those of cPLA2 (P = 0.15). The addition of FSH
      increased the levels of COX-2 (P = 0.01) but, it had no effect on the
      concentration of PGE2 (P = 0.08) or on the levels of OTR (P = 0.07) and cPLA2 (P
      = 0.15). Oxytocin did not increase the levels of COX-2 (P = 0.38) but increased
      those of OTR (P = 0.001) and cPLA2 (P = 0.01) but not on the concentration of
      PGE2 in the media. Arachidonic acid increased the levels of cPLA2 (P = 0.01) and
      those of COX-2 (P = 0.02) but not the concentration of PGE2 in the media. Our
      findings suggest that the PGE2-mediated mechanisms of cervical relaxation in the
      ewe during the follicular phase are stimulated by FSH, 17beta-estradiol,
      oxytocin, and AA. They all appear to act by inducing receptors and enzymes along
      the synthetic pathway for PGE2. 

PMID- 25586642
TI  - Fringing reefs exposed to different levels of eutrophication and sedimentation
      can support similar benthic communities.
AB  - Benthic communities are sensitive to anthropogenic disturbances which can result
      in changes in species assemblages. A spatio-temporal survey of environmental
      parameters was conducted over an 18-month period on four different fringing reefs
      of Moorea, French Polynesia, with unusual vs. frequent human pressures. This
      survey included assessment of biological, chemical, and physical parameters.
      First, the results showed a surprising lack of a seasonal trend, which was likely
      obscured by short-term variability in lagoons. More frequent sampling periods
      would likely improve the evaluation of a seasonal effect on biological and
      ecological processes. Second, the three reef habitats studied that were dominated
      by corals were highly stable, despite displaying antagonistic environmental
      conditions through eutrophication and sedimentation gradients, whereas the reef
      dominated by macroalgae was relatively unstable. Altogether, our data challenge
      the paradigm of labelling environmental parameters such as turbidity,
      sedimentation, and nutrient-richness as stress indicators. 

PMID- 25586641
TI  - Optimizing cofactor availability for the production of recombinant heme
      peroxidase in Pichia pastoris.
AB  - BACKGROUND: Insufficient incorporation of heme is considered a central impeding
      cause in the recombinant production of active heme proteins. Currently, two
      approaches are commonly taken to overcome this bottleneck; metabolic engineering
      of the heme biosynthesis pathway in the host organism to enhance intracellular
      heme production, and supplementation of the growth medium with the desired
      cofactor or precursors thereof to allow saturation of recombinantly produced apo
      forms of the target protein. In this study, we investigated the effect of both,
      pathway engineering and medium supplementation, to optimize the recombinant
      production of the heme protein horseradish peroxidase in the yeast Pichia
      pastoris. RESULTS: In contrast to studies with other hosts, co-overexpression of
      genes of the endogenous heme biosynthesis pathway did not improve the recombinant
      production of active heme protein. However, medium supplementation with hemin
      proved to be an efficient strategy to increase the yield of active enzyme,
      whereas supplementation with the commonly used precursor 5-aminolevulinic acid
      did not affect target protein yield. CONCLUSIONS: The yield of active recombinant
      heme peroxidase from P. pastoris can be easily enhanced by supplementation of the
      cultivation medium with hemin. Thereby, secreted apo-species of the target
      protein are effectively saturated with cofactor, maximizing the yield of target
      enzyme activity.

PMID- 25586644
TI  - Ozonated saline shows activity against planktonic and biofilm growing
      Staphylococcus aureus in vitro: a potential irrigant for infected wounds.
AB  - Infections associated with deep wounds require extensive surgical and medical
      care. New adjunctive treatments are required to aid in the eradication of the
      bacterial biofilms found on infected wounds and, in particular, any underlying
      hardware. Ozone has been used as a safe and efficient disinfectant in water
      treatment plants for many years. The purpose of this study is to investigate the
      anti-biofilm potential of ozonated saline against biofilms of Staphylococcus
      aureus, a microorganism commonly implicated in wound infections. A custom-made
      bacterial biofilm bioreactor was used to grow S. aureus biofilms on discs of
      medical grade titanium alloy. An ozone generator was connected in-line and
      biofilms and planktonic bacteria were exposed to ozone in saline. Cytotoxicity
      was assessed against primary ovine osteoblasts in the same system. In tests
      against planktonic S. aureus, a 99% reduction in bacterial numbers was detected
      within 15 minutes of exposure. S. aureus biofilms were significantly more
      resistant to ozone, although complete eradication of the biofilm was eventually
      achieved within 5 hours. Ozonated saline was not found to be cytotoxic to primary
      ovine osteoblasts. Ozonated saline may be suitable as an adjuvant therapy to
      treat patients as an instillation fluid for wound irrigation and sterilisation. 

PMID- 25586643
TI  - Signaling between two interacting sensor kinases promotes biofilms and
      colonization by a bacterial symbiont.
AB  - Cells acclimate to fluctuating environments by utilizing sensory circuits. One
      common sensory pathway used by bacteria is two-component signaling (TCS),
      composed of an environmental sensor [the sensor kinase (SK)] and a cognate,
      intracellular effector [the response regulator (RR)]. The squid symbiont Vibrio
      fischeri uses an elaborate TCS phosphorelay containing a hybrid SK, RscS, and two
      RRs, SypE and SypG, to control biofilm formation and host colonization. Here, we
      found that another hybrid SK, SypF, was essential for biofilms by functioning
      downstream of RscS to directly control SypE and SypG. Surprisingly, although wild
      type SypF functioned as an SK in vitro, this activity was dispensable for
      colonization. In fact, only a single non-enzymatic domain within SypF, the HPt
      domain, was critical in vivo. Remarkably, this domain within SypF interacted with
      RscS to permit a bypass of RscS's own HPt domain and SypF's enzymatic function.
      This represents the first in vivo example of a functional SK that exploits the
      enzymatic activity of another SK, an adaptation that demonstrates the elegant
      plasticity in the arrangement of TCS regulators. 

PMID- 25586645
TI  - Challenges in measuring the societal value of orphan drugs: insights from a
      canadian stated preference survey.
AB  - BACKGROUND: Expensive drugs for rare diseases (i.e. orphan drugs) often do not
      meet traditional cost-effectiveness criteria and thus put further strain on
      limited healthcare budgets. Failing to provide medically necessary care to
      patients, however, violates one of the underlying tenets of most public health
      insurance systems-equity. This has led payers to consider the value that society
      places on the treatment of rare diseases, given the opportunity cost, when
      deciding on whether to fund specific treatments. AIMS: In this article we aim to
      illustrate two factors that make the measurement of societal value in this area
      particularly difficult: the low level of public awareness of, and engagement
      with, the orphan-drug issue, and the 'zero-sum' framing commonly used to describe
      the policy challenge posed by orphan drugs. METHOD: We illustrate these
      challenges using data from an original survey of 2,005 Canadian adults.
      Respondents completed two tasks in which they were asked to choose between
      funding the treatment of patients suffering from either rare or common diseases.
      RESULTS: Respondents were more likely to display choice aversion and unstable
      preferences if they had not completed a university degree and when a 'zero-sum'
      frame was used to introduce the choice sets. CONCLUSIONS: The results suggest
      that studies in which the stated opportunity costs of funding orphan drugs focus
      exclusively on reductions in funding for other drugs or treatments may only
      provide a limited understanding of citizens' policy preferences in the area of
      rare diseases.

PMID- 25586646
TI  - Measuring the Preferences of Homeless Women for Cervical Cancer Screening
      Interventions: Development of a Best-Worst Scaling Survey.
AB  - OBJECTIVE: Despite having multiple risk factors, women experiencing homelessness
      are screened for cervical cancer at a lower rate than women in the general US
      population. We report on the design of a stated preference study to assess
      homeless women's preferences for cervical cancer screening interventions, to
      inform efforts to overcome this disparity. METHODS: We conducted focus groups
      with homeless women (n = 8) on cervical cancer screening decisions and analyzed
      the data using thematic analysis. We applied inclusion criteria to select factors
      for a stated preference survey: importance to women, relevance to providers,
      feasibility, and consistency with clinical experience. We conducted pretests (n =
      35) to assess survey procedures (functionality, recruitment, administration) and
      content (understanding, comprehension, wording/language, length). RESULTS: We
      chose best-worst scaling (BWS)-also known as object scaling-to identify decision
      relevant screening intervention factors. We chose an experimental design with 11
      "objects" (i.e., factors relevant to women's screening decision) presented in 11
      subsets of five objects each. Of 25 objects initially identified, we selected 11
      for the BWS instrument: provider-related factors: attitude, familiarity, and
      gender; setting-related factors: acceptance and cost; procedure-related factors:
      explanation during visit and timing/convenience of visit; personal fears and
      barriers: concerns about hygiene, addiction, and delivery/fear of results; and a
      general factor of feeling overwhelmed. CONCLUSION: Good practices for the
      development of stated preference surveys include considered assessment of the
      experimental design that is used and the preference factors that are included,
      and pretesting of the presentation format. We demonstrate the development of a
      BWS study of homeless women's cervical cancer screening intervention preferences.
      Subsequent research will identify screening priorities to inform intervention
      design.

PMID- 25586647
TI  - The prevalence of Hymenolepis nana among preschool children of displacement
      communities in Khartoum state, Sudan: a cross-sectional study.
AB  - BACKGROUND: Hymenolepis nana is among the most common intestinal parasitic
      infections causing a public health threat in poor communities in Sub-Saharan
      Africa. The present study was conducted to determine the prevalence of H. nana
      infections and associated risk factors among preschool children of displacement
      communities in Khartoum state, Sudan. METHODS: A cross-sectional survey was
      conducted in May 2013 in displacement camps, Khartoum state, Sudan. A simple
      random sample of preschool children from the displacement camps, aged between 1
      and 5 years, were included. Information was collected by presenting a
      questionnaire and taking 500 fresh stool specimens which were examined
      microscopically for the presence of eggs, using direct saline and formal-ether
      concentration techniques. RESULTS: The prevalence of H. nana was determined to be
      32.6% (163/500), 95% CI (28.5%-36.9%). Infections of H. nana were more prevalent
      among males than females, and this association was statistically significant (P <
      0.001, OR = 2.125, 95% CI = 1.452-3.108). H. nana infections were significantly
      prevalent among the older age group (2.6-5.0 years) (P < 0.001, OR = 2.909, 95%
      CI = 1.914-4.420). Approximately 76.7% of infected preschool children had
      diarrhea and it was significantly associated with H. nana infection (P < 0.001,
      OR = 9.45, 95% CI = 6.10-14.64). None of the preschool children had access to a
      clean water supply. No significant association was found between use of latrines
      and infections of H. nana (P = 0.56, OR = 0.880, 95% CI = 0.73-1.763).
      CONCLUSIONS: There was a high prevalence rate of H. nana infection among
      preschool children of displacement camps in Khartoum state, Sudan. Being male,
      aged between 2.6 and 5.0 years, and having diarrhea were identified as important
      risk factors for H. nana infection. Measures including health education,
      environmental hygiene, water supply and treatment should be taken into account to
      reduce the high prevalence of H. nana.

PMID- 25586649
TI  - A LINE-1-encoded reverse transcriptase-dependent regulatory mechanism is active
      in embryogenesis and tumorigenesis.
AB  - LINE-1 (long interspersed nuclear elements) retrotransposons constitute a large
      family of retrotransposable elements, accounting for 17% of the human genome.
      They encode proteins required for their own mobilization, including a reverse
      transcriptase (RT) enzyme highly expressed in mouse embryos and mouse and human
      cancer cells and repressed in somatic differentiated healthy cells. We have found
      that reverse transcription takes place in early murine embryos, yielding an
      increase in LINE-1 copy number during preimplantation development, which also
      occurs in tumor progression. RT inhibition irreversibly arrests embryo
      development, reduces cancer cell proliferation, promotes differentiation,
      antagonizes tumor growth, and causes a global reprogramming of transcription
      profiles. These results strongly suggest that a previously unrecognized RT
      dependent regulatory mechanism operates during preimplantation development, is
      repressed during differentiation to normal tissues, and, when erroneously
      reactivated in adult life, promotes cell transformation and cancer progression by
      "resurrecting" embryonic transcriptional pathways. The RT-dependent mechanism
      emerges as a major source of genetic and epigenetic changes with physiological,
      pathological, and evolutionary implications.

PMID- 25586648
TI  - A secondary dengue 4 infection in a traveler returning from Haiti confirmed by
      virus isolation, complete genome sequencing and neutralisation assay: a brief
      report.
AB  - Here we report the clinical and laboratory findings of a dengue 4 virus (DENV)
      secondary infection in a patient returning from Haiti to France. The diagnostic
      of acute DEN-4 virus infection was demonstrated by (i) the presence of DEN-4 RNA
      in two successive serum samples, (ii) the isolation of a DEN-4 virus in Vero
      cells and subsequent identification of subtype IIb through complete genome
      sequencing, (iii) the presence of dengue NS1 antigen, (iv) the seroconversion
      with detection of dengue IgM in the second serum while negative in the first
      serum. The diagnosis of secondary dengue episode was demonstrated by (i) the
      presence of dengue IgG in the early serum, and (ii) the demonstration that
      neutralising antibodies against DEN-3 were present at the acute stage of the
      disease. Next-generation sequencing has a primary role to play in phylogeographic
      studies including database sequences, sequences from imported cases, and
      sequences from autochthonous cases. 

PMID- 25586650
TI  - Synergistic strengthening of polyelectrolyte complex membranes by functionalized
      carbon nanotubes and metal ions.
AB  - Hydrophilic polymers have garnered much attention due to their critical roles in
      various applications such as molecular separation membranes, bio-interfaces, and
      surface engineering. However, a long-standing problem is that their mechanical
      properties usually deteriorate at high relative humidity (RH). Through the
      simultaneous incorporation of functionalized carbon nanotubes and copper ions
      (Cu(2+)), this study introduces a facile method to fabricate high strength
      polyelectrolyte complex nanohybrid membranes resistant to high RH (90%). For
      example, the tensile strength of the nanohybrid membranes is 55 MPa at 90% RH
      (80% of the original value at 30% RH). These results are explained by copper ions
      depressing the swelling degree of the membrane, and functionalized carbon
      nanotubes promoting stress transfer between the polymer matrix and them. The
      nanohybrid membranes are efficient in separating water/alcohol mixtures
      containing relatively high water content (up to 30 wt%), whereas common
      hydrophilic polymer membranes usually suffer from excessive swelling under this
      condition.

PMID- 25586652
TI  - Predictors of AA amyloidosis in familial Mediterranean fever.
AB  - The aim of the study was to evaluate the clinical and genetic predictors of AA
      amyloidosis in patients with familial Mediterranean fever (FMF). We
      retrospectively studied 170 Armenian patients who were admitted to the two
      tertiary centers in 2003-2014. The diagnosis of amyloidosis that was suspected
      clinically (new proteinuria or nephrotic syndrome) was confirmed histologically.
      Screening for MEFV gene mutations was performed in 70 patients. The most common
      genotype was M694V/M694V (in 36 % of patients). Biopsy-proven AA amyloidosis was
      found in 102 (60 %) of 170 patients. AA amyloidosis was diagnosed in 17 (68 %) of
      25 patients with homozygous M694V mutation, 17 (53 %) of 32 patients with
      heterozygous M694V allele and 4 (31 %) of 13 patients with other MEFV gene
      mutations. The M694V homozygosity and heterozygosity were associated with
      increased risk of AA amyloidosis, but this association did not reach statistical
      significance (odds ratio 2.43; 95 % CI 0.87-6.76, and 3.33; 0.91-12.1,
      respectively). Male gender, early onset of disease, severity of FMF, frequent
      attacks, peritonitis, pleuritis and erysipelas-like erythema also did not predict
      AA amyloidosis development. Recurrent arthritis was the only clinical finding
      that was significantly associated with AA amyloidosis (odds ratio 2.28; 95 % CI
      1.17-4.42). Involvement of the joint synovial membrane, that is capable of active
      serum amyloid A production, is the main predictor of renal amyloidosis in FMF. 

PMID- 25586651
TI  - Evidence-based clinical practice guidelines for functional dyspepsia.
AB  - General interest in functional gastrointestinal disorders is increasing among
      Japanese doctors as well as patients. This increase can be attributed to a number
      of factors, including recent increased interest in quality of life and advances
      in our understanding of the pathophysiology of gastrointestinal disease. Japan
      recently became the world's first country to list "functional dyspepsia" as a
      disease name for national insurance billing purposes. However, recognition and
      understanding of functional dyspepsia (FD) remain poor, and no standard treatment
      strategy has yet been established. Accordingly, the Japanese Society of
      Gastroenterology (JSGE) developed an evidence-based clinical practice guideline
      for FD, consisting of five sections: concept, definition, and epidemiology;
      pathophysiology; diagnosis; treatment; and prognosis and complications. This
      article summarizes the Japanese guideline, with particular focus on the treatment
      section. Once a patient is diagnosed with FD, the doctor should carefully explain
      the pathophysiology and benign nature of this condition, establish a good doctor
      patient relationship, and then provide advice for daily living (diet and
      lifestyle modifications, explanations, and reassurance). The proposed
      pharmacological treatment is divided into two steps: initial treatment including
      an acid inhibitory drug (H2RA or PPI) or prokinetics, (strong recommendation);
      second-line treatment including anxiolytics, antidepressants, and Japanese
      traditional medicine (weak recommendation). H. pylori eradication, strongly
      recommended with a high evidence level, is positioned separately from other
      treatment flows. Conditions that do not respond to these treatment regimens are
      regarded as refractory FD. Patients will be further examined for other organic
      disorders or will be referred to specialists using other approaches such as
      psychosomatic treatment. 

PMID- 25586653
TI  - Dissecting the damage in Northern Greek patients with childhood-onset systemic
      lupus erythematosus: a retrospective cohort study.
AB  - The improved survival of childhood-onset systemic lupus erythematosus (cSLE) has
      resulted in longer patients' exposure to disease inflammation, medications and/or
      comorbid diseases, which can all contribute to the development of organ damage.
      The aim of this study was to assess the evolution of damage accrual in cSLE
      patients overtime and investigate for predisposing factors. Disease
      characteristics and treatment in 47 Northern Greek Caucasian cSLE patients were
      retrospectively reviewed. The Systemic Lupus International Collaboration
      Clinics/American College of Rheumatology Damage Index (SDI) was used for damage
      assessment and the European Consensus Lupus Activity Measurement (ECLAM) to
      monitor cSLE activity. After a median disease duration of 7.4 years, 17/47
      patients (36 %) had developed damage (SDI > 0). The most frequent domains damaged
      were the ocular (41 %), neuropsychiatric (35 %) and peripheral vascular (35 %)
      one. Peripheral vascular and neuropsychiatric damage was seen more frequently
      during the first 5 years of the disease. Longer exposure to azathioprine was
      associated with higher SDI at the end of follow-up (beta = 0.008 for every
      additional month of use, p = 0.041). The mean annual flare frequency was
      associated with a shorter time interval until the development of the first damage
      (hazard's ratio, HR 2.38 for each unit of increase, p = 0.018), while
      hydroxychloroquine use was associated with longer time interval (HR 0.19, p =
      0.007). The lower rates of damage accrual in this study compared to other cohorts
      might be due to milder disease phenotype in Greek Caucasian cSLE patients, prompt
      diagnosis and effective disease control. Damage was noticed early in the disease
      course, and one-third of patients had an SDI > 0 at study completion. Disease
      flares and a severe disease course leading to prolonged use of immunosuppressives
      were significant risk factors, while hydroxychloroquine use was protective
      against cSLE damage accrual. 

PMID- 25586654
TI  - The association between comorbidities and pain, physical function and quality of
      life following hip and knee arthroplasty.
AB  - The aim of the study was to examine the relationship between comorbidities and
      pain, physical function and health-related quality of life (HRQoL) after total
      hip arthroplasty (THA) and total knee arthroplasty (TKA). A cross-sectional
      retrospective survey was conducted including 19 specific comorbidities,
      administered in patients who underwent THA or TKA in the previous 7-22 months in
      one of 4 hospitals. Outcome measures included pain, physical functioning, and
      HRQoL. Of the 521 patients (281 THA and 240 TKA) included, 449 (86 %) had >=1
      comorbidities. The most frequently reported comorbidities (>15 %) were severe
      back pain; neck/shoulder pain; elbow, wrist or hand pain; hypertension;
      incontinence of urine; hearing impairment; vision impairment; and cancer. Only
      the prevalence of cancer was significantly different between THA (n = 38; 14 %)
      and TKA (n = 52; 22 %) (p = 0.01). The associations between a higher number of
      comorbidities and worse outcomes were stronger in THA than in TKA. In
      multivariate analyses including all comorbidities with a prevalence of >5 %, in
      THA dizziness in combination with falling and severe back pain, and in TKA
      dizziness in combination with falling, vision impairments, and elbow, wrist or
      hand pain was associated with worse outcomes in most of the analyses. A broad
      range of specific comorbidities needs to be taken into account with the
      interpretation of patients' health status after THA and TKA. More research
      including the ascertainment of comorbidities preoperatively is needed, but it is
      conceivable that in particular, the presence of dizziness with falling, pain in
      other joints, and vision impairments should be assessed and treated in order to
      decrease the chance of an unfavorable outcome. 

PMID- 25586655
TI  - Dimeric Cinchona alkaloids.
AB  - Nature is full of dimeric alkaloids of various types from many plant families,
      some of them with interesting biological properties. However, dimeric Cinchona
      alkaloids were not isolated from any species but were products of designed
      partial chemical synthesis. Although the Cinchona bark is amongst the sources of
      oldest efficient medicines, the synthetic dimers found most use in the field of
      asymmetric synthesis. Prominent examples include the Sharpless dihydroxylation
      and aminohydroxylation ligands, and dimeric phase transfer catalysts. In this
      article the syntheses of Cinchona alkaloid dimers and oligomers are reviewed, and
      their structure and applications are outlined. Various synthetic routes exploit
      reactivity of the alkaloids at the central 9-hydroxyl group, quinuclidine, and
      quinoline rings, as well as 3-vinyl group. This availability of reactive sites,
      in combination with a plethora of linker molecules, contributes to the diversity
      of the products obtained. 

PMID- 25586656
TI  - Synthesis of C-glycosyl-bis-1,2,3-triazole derivatives from 3,4,6-tri-O-acetyl-D
      glucal.
AB  - We have developed an efficient, CuI-catalyzed, microwave-assisted method for the
      synthesis of bis-1,2,3-triazole derivatives starting from a 3,4,6-tri-O-acetyl-D
      glucal-derived mesylate. This mesylate was obtained from 3,4,6-tri-O-acetyl-D
      glucal through C-glycosidation, deprotection of acetate groups to alcohols, and
      selective mesylation of the primary alcohol. This mesylate moiety was then
      converted to an azide through a microwave-assisted method with good yield. The
      azide, once synthesized, was then treated with different terminal alkynes in the
      presence of CuI to synthesize various bis-triazoles in high yields and short
      reaction times.

PMID- 25586657
TI  - Urticarial vasculitis and urticarial autoinflammatory syndromes.
AB  - Urticaria is a frequent disorder classified as acute and chronic forms, which
      presents with wheals that can be associated with angioedema. Several entities may
      manifest with urticarial skin lesions, encompassing a heterogeneous group of
      conditions that have to be differentiated from ordinary urticaria. This review is
      focused on two of these urticarial syndromes: urticarial vasculitis (UV), which
      represents the most important differential diagnosis with common urticaria, and
      autoinflammatory diseases such as cryopyrin-associated periodic syndromes (CAPS)
      and Schnitzler's Syndrome, both rare multisystem forms that may masquerade as
      common urticaria. UV is a small-vessel vasculitis with predominant skin
      involvement, characterized by wheals persisting for more than 24 hours, burning
      rather than itching and resolving with hyperpigmentation as well as by other
      cutaneous manifestations including purpura, papules, vesicles, bullae and
      necrotic-ulcerative lesions. Histology shows a classic pattern of
      leukocytoclastic vasculitis, with possible presence of upper dermal edema. CAPS
      are classified as three distinct entities: familial cold autoinflammatory
      syndrome, Muckle-Wells Syndrome and chronic infantile neurological cutaneous and
      articular syndrome, which represent a spectrum of disorders caused by different
      mutations in a single gene, NLRP3 (NOD-like receptor 3). This gene encodes for
      cryopyrin, an inflammasome protein that activates interleukin-1beta, leading to
      an overproduction of this pivotal proinflammatory cytokine. Histologically,
      urticarial lesions are generally characterized by a perivascular neutrophilic
      infiltrate. Unlike urticaria, neither UV nor urticarial autoinflammatory
      syndromes do respond to antihistamines: thus, it is important not to misdiagnose
      such conditions in order to give the patients specific treatments, potentially
      preventing serious systemic complications. 

PMID- 25586658
TI  - Metastatic breast carcinoma of the jugular foramen: a rare case of Villaret
      syndrome.
AB  - BACKGROUND: The differential diagnosis of skull base masses is diverse and
      includes benign and malignant neoplasms, vascular anomalies, congenital lesions,
      as well as infectious and inflammatory processes. Metastatic masses of the skull
      base are a rare manifestation of systemic malignancies. Breast cancer is the most
      common cause of skull base metastases. Villaret syndrome refers to cranial nerves
      IX, X, XI, and XII and sympathetic chain neuropathies. It is a clinical subtype
      of jugular foramen syndromes. METHODS AND RESULTS: A 62-year-old woman with a
      history of breast carcinoma presented with hoarseness dating to shortly after her
      mastectomy years earlier. CT angiography showed enhancing tissue just outside the
      right jugular foramen, and biopsy confirmed metastatic adenocarcinoma consistent
      with breast cancer. CONCLUSION: Villaret syndrome caused by breast cancer
      metastases has not been previously described. We present a case of Villaret
      syndrome caused by metastasis of invasive breast adenocarcinoma and a review of
      the literature of metastases of breast cancer to the skull base.

PMID- 25586659
TI  - Selective lesions of the cholinergic neurons within the posterior
      pedunculopontine do not alter operant learning or nicotine sensitization.
AB  - Cholinergic neurons within the pedunculopontine tegmental nucleus have been
      implicated in a range of functions, including behavioral state control,
      attention, and modulation of midbrain and basal ganglia systems. Previous
      experiments with excitotoxic lesions have found persistent learning impairment
      and altered response to nicotine following lesion of the posterior component of
      the PPTg (pPPTg). These effects have been attributed to disrupted input to
      midbrain dopamine systems, particularly the ventral tegmental area. The pPPTg
      contains a dense collection of cholinergic neurons and also large numbers of
      glutamatergic and GABAergic neurons. Because these interdigitated populations of
      neurons are all susceptible to excitotoxins, the effects of such lesions cannot
      be attributed to one neuronal population. We wished to assess whether the
      learning impairments and altered responses to nicotine in excitotoxic PPTg
      lesioned rats were due to loss of cholinergic neurons within the pPPTg. Selective
      depletion of cholinergic pPPTg neurons is achievable with the fusion toxin Dtx
      UII, which targets UII receptors expressed only by cholinergic neurons in this
      region. Rats bearing bilateral lesions of cholinergic pPPTg neurons (>90% ChAT+
      neuronal loss) displayed no deficits in the learning or performance of fixed and
      variable ratio schedules of reinforcement for pellet reward. Separate rats with
      the same lesions had a normal locomotor response to nicotine and furthermore
      sensitized to repeated administration of nicotine at the same rate as sham
      controls. Previously seen changes in these behaviors following excitotoxic pPPTg
      lesions cannot be attributed solely to loss of cholinergic neurons. These
      findings indicate that non-cholinergic neurons within the pPPTg are responsible
      for the learning deficits and altered responses to nicotine seen after
      excitotoxic lesions. The functions of cholinergic neurons may be related to
      behavioral state control and attention rather than learning.

PMID- 25586660
TI  - Treatment patterns and clinical outcomes in patients with chronic immune
      thrombocytopenia (ITP) switched to eltrombopag or romiplostim.
AB  - This observational study aimed to assess real-world treatment patterns and
      clinical outcomes for patients with chronic immune thrombocytopenia (ITP)
      currently being treated with eltrombopag or romiplostim after switching from
      corticosteroids, rituximab, or the alternate thrombopoietin receptor agonist (TPO
      RA). The study examined the rationale for switching to TPO-RA therapy using aided
      responses. Dosing patterns were also analyzed before and after switching.
      Treatment outcomes were assessed through platelet counts at multiple time points
      including treatment initiation and after switching at the last office visit. A
      total of 280 patients were enrolled whose active therapy for ITP was replaced
      with either eltrombopag (n = 130) or romiplostim (n = 150). Efficacy-related
      issues (desired platelet count not achieved and/or lack of response to prior
      therapy) were the main drivers for therapy switching among all patients (54 % for
      eltrombopag vs. 57 % for romiplostim). Platelet counts at the last office visit
      showed improvement compared with counts at the initiation of either eltrombopag
      or romiplostim treatment. No significant differences were noted when comparing
      clinical outcomes between the eltrombopag and romiplostim treatment cohorts. Our
      results suggest that switching to the other TPO-RA may be beneficial if there is
      inadequate response to treatment with the initial TPO-RA.

PMID- 25586661
TI  - Anthocyanins as substrates for mitochondrial complex I - protective effect
      against heart ischemic injury.
AB  - Anthocyanins, a subclass of flavonoids, are known to protect against myocardial
      ischemia; however, little is known about their direct, acute effects on
      mitochondria injured by the ischemic insult. In this study, the effects of
      delphinidin 3-O-glucoside (Dp3G), cyanidin 3-O-glucoside (Cy3G) and pelargonidin
      3-O-glucoside (Pg3G) on the activity of complex I of the mitochondrial
      respiratory chain were studied in mitochondria isolated from normal rat hearts
      and rat hearts subjected to ischemia for 45 min. Cy3G and Dp3G increased the
      activity of complex I, measured in the presence or absence of coenzyme Q1 (CoQ1
      ), in ischemia-damaged mitochondria, whereas in nonischemic mitochondria the
      effect was observed only in the absence of CoQ1 . Dp3G and Cy3G but not Pg3G
      increased state 3 respiration and ATP synthesis with NADH-dependent substrates in
      mitochondria after ischemia. The results suggest that certain anthocyanins can
      act as electron acceptors at complex I, and bypass ischemia-induced inhibition,
      resulting in increased ATP production after ischemia. This study provides new
      information on a possible role of certain anthocyanins in the regulation of
      energy metabolism in mammalian cells.

PMID- 25586663
TI  - Reversal by ranolazine of doxorubicin-induced prolongation in the inactivation of
      late sodium current in rat dorsal root ganglion neurons.

PMID- 25586662
TI  - Association of immunoexpression of the galectins-3 and -7 with histopathological
      and clinical parameters in oral squamous cell carcinoma in young patients.
AB  - An increasing incidence of oral squamous cell carcinoma (OSCC) in individuals
      younger than 45 years has been observed in recent years. OSCC in younger patients
      differs in terms of biological behavior and prognosis with the disease being more
      aggressive than in older patients. The aim of this study was to analyze the
      immunohistochemical expression of galectins-3 and -7 in 32 cases of OSCC in young
      patients and to correlate this expression with clinical and morphological
      parameters. All cases of OSCC of the sample were diagnosed at oncology referral
      hospitals in Paraiba, Brazil, between 2002 and 2012. Clinical data were obtained
      from the patient records. Histological malignancy grading systems proposed by
      Bryne et al. (J Pathol 166:375-381, 1992) and the World Health Organization (In:
      Pathology and genetics of head and neck tumours: Word Health Organization
      classification of tumours, 2005) were used for morphological analysis.
      Immunohistochemistry was performed by the streptavidin-biotin technique using
      anti-galectin-3 and -7 antibodies. The results were analyzed statistically by the
      Chi-squared and Fisher exact tests (p < 0.05). Immunoexpression of galectin-3 was
      observed in 65.6 % of the cases analyzed, but showed no significant association
      with any of the variables studied (clinical staging; histological malignancy
      grading systems). Immunoexpression of galectin-7 was observed in 96.9 % of cases
      and was significantly associated with histological malignancy grading systems (p
      < 0.05). In conclusion, the results suggest the use of galectin-7 as marker of
      biological behavior and tumor progression in OSCC in young patients.

PMID- 25586664
TI  - Complex association between body weight and fracture risk in postmenopausal
      women.
AB  - Osteoporosis is a common disease, characterized by low bone mass with micro
      architectural disruption and skeletal fragility, resulting in an increased risk
      of fracture. A substantial number of studies has examined the possible
      relationship between body weight, bone mineral density and fracture risk in post
      menopausal women, with the majority of them concluding that low body weight
      correlates with increased risk of fracture, especially hip fracture.
      Controversies about the potential protective effect of obesity on osteoporosis
      and consequent fracture risk still exist. Several recent studies question the
      concept that obesity exerts a protective effect against fractures, suggesting
      that it stands as a risk factor for fractures at specific skeletal sites, such as
      upper arm. The association between body weight and fracture risk is complex,
      differs across skeletal sites and body mass index, and is modified by the
      interaction between body weight and bone mineral density. Some potential
      explanations that link obesity with increased fracture risk may be the pattern of
      falls and impaired mobility in obese individuals, comorbidities, such as asthma,
      diabetes and early menopause, as well as, increased parathyroid hormone and
      reduced 25-hydroxy-vitamin D concentrations. 

PMID- 25586665
TI  - Posterosuperior glenoid internal impingement of the shoulder in the overhead
      athlete: pathogenesis, clinical features and MR imaging findings.
AB  - Posterosuperior glenoid internal impingement (PGII) is an impingement syndrome of
      the shoulder that is most commonly seen in the throwing or overhead athlete. The
      supraspinatus can be normally compressed or impinged between the greater
      tuberosity and the posterosuperior labrum in the abduction and external rotation
      position. However, repetitive throwing and biomechanical abnormalities may lead
      to the intensification of this contact and to the clinical and pathological
      picture of PGII. The injured athlete usually complains of poor throwing
      performance and pain located in the posterosuperior aspect of the shoulder. Two
      main theories regarding the aetiology of PGII have been postulated with differing
      initial mechanisms. The MRI features of PGII have been described and include
      supraspinatus and anterior infraspinatus partial undersurface tears, bony changes
      at the humeral head and labral pathology, including a variation of the type II
      superior labrum from anterior to posterior lesion. This pictorial essay aims to
      present cases illustrating the pathophysiology, clinical features and recently
      described MRI findings, and discuss some of the MR protocol considerations. 

PMID- 25586667
TI  - Surface properties of heat-induced soluble soy protein aggregates of different
      molecular masses.
AB  - Suspensions (2% and 5%, w/v) of soy protein isolate (SPI) were heated at 80, 90,
      or 100  degrees C for different time periods to produce soluble aggregates of
      different molecular sizes to investigate the relationship between particle size
      and surface properties (emulsions and foams). Soluble aggregates generated in
      these model systems were characterized by gel permeation chromatography and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Heat treatment
      increased surface hydrophobicity, induced SPI aggregation via hydrophobic
      interaction and disulfide bonds, and formed soluble aggregates of different
      sizes. Heating of 5% SPI always promoted large-size aggregate (LA; >1000 kDa)
      formation irrespective of temperature, whereas the aggregate size distribution in
      2% SPI was temperature dependent: the LA fraction progressively rose with
      temperature (80->90->100  degrees C), corresponding to the attenuation of medium
      size aggregates (MA; 670 to 1000 kDa) initially abundant at 80  degrees C. Heated
      SPI with abundant LA (>50%) promoted foam stability. LA also exhibited excellent
      emulsifying activity and stabilized emulsions by promoting the formation of small
      oil droplets covered with a thick interfacial protein layer. However, despite a
      similar influence on emulsion stability, MA enhanced foaming capacity but were
      less capable of stabilizing emulsions than LA. The functionality variation
      between heated SPI samples is clearly related to the distribution of aggregates
      that differ in molecular size and surface activity. The findings may encourage
      further research to develop functional SPI aggregates for various commercial
      applications. 

PMID- 25586668
TI  - The feasibility of coin motors for use in a vibrotactile display for the blind.
AB  - We have tested the potential of three types of vibration motors for use in a
      tactile vision substitution device for the blind. The motors were of the coin
      type, which are available off-the-shelf, and are characterized by their
      affordability, energy efficiency, and ease of implementation. The primary
      limitation of coin motors is the lack of control they offer over stimulus
      parameters. Specifically, adjusting the input voltage of a coin motor not only
      changes the vibration intensity, but also the vibration frequency and duration.
      This characteristic may result in unpredictable perceptions in psychophysical
      tests. By using standard psychophysical procedures, we were able to show that the
      tested coin motors evoked predictable magnitude perceptions across their dynamic
      range, following Fechner's law as if vibration intensity alone were varied. The
      best-performing motor was able to generate a median number of 15 available just
      noticeable differences, meaning that it was potentially capable of conveying 16
      gray levels in its dynamic range. We conclude that coin motors are potential
      candidates for the construction of a tactile display to substitute for lost
      vision. 

PMID- 25586666
TI  - Upregulation of miR-142-5p in atherosclerotic plaques and regulation of oxidized
      low-density lipoprotein-induced apoptosis in macrophages.
AB  - MicroRNA (miR)-142-5p is a member of the miR-142 family, which have been shown to
      be associated with tumors, stem cells and disorders of the immune system.
      However, the role of miR-142-5p in atherosclerosis has yet to be investigated. In
      the present study, an atherosclerotic apolipoprotein E-deficient (apoE-/-) mouse
      model was constructed and fed a high-fat diet. The expression levels of miR-142
      5p in the murine atherosclerotic plaques were detected by gene microarray
      analysis. In addition, an in vitro assay was used to determine the expression
      levels of miR-142-5p in human endothelial cells, smooth muscle cells and
      macrophages, which were treated with oxidized low-density lipoprotein (ox-LDL).
      Furthermore, a miR-142-5p inhibitor and mimic was transfected into cultured human
      macrophages, in order to observe the effects on transforming growth factor-beta2
      (TGF-beta2) expression. The effects of co-transfection of the miR-142-5p
      inhibitor or mimic with TGF-beta2, in human macrophages, on the rate of apoptosis
      was analyzed. The expression levels of miR-142-5p were 6.84-fold higher in mice
      with stable atherosclerotic plaques, and 2.69-fold higher in mice with vulnerable
      atherosclerotic plaques, as compared with the controls. Furthermore, the
      expression levels of miR-142-5p were upregulated in the cultured human
      macrophages. The percentage of apoptotic cells was lowest in the macrophages
      transfected with both TGF-beta2 and miR-142-5p inhibitors and treated with ox
      LDL. The expression levels of miR-142-5p were upregulated in the atherosclerotic
      plaques of the apoE-/- mice. The findings of the present study have shown that
      the upregulation of miR-142-5p expression may regulate apoptosis in human
      macrophages by targeting TGF-beta2. This effect may have an important role in the
      progression of atherosclerosis.

PMID- 25586670
TI  - Brown adipose tissue triglyceride content is associated with decreased insulin
      sensitivity, independently of age and obesity.
AB  - The aim of the present study was to determine whether single-voxel proton
      magnetic resonance spectroscopy ((1)H-MRS) can non-invasively assess triglyceride
      content in both supraclavicular fat depots and subcutaneous white adipose tissue
      (WAT) to determine whether these measurements correlate to metabolic variables. A
      total of 25 healthy volunteers were studied using (18)F-fluorodeoxyglucose
      positron emission tomography (PET) and (15)O-H2O PET perfusion during cold
      exposure, and (1)H-MRS at ambient temperature. Image-guided biopsies were
      collected from nine volunteers. The supraclavicular triglyceride content
      determined by (1)H-MRS varied between 60 and 91% [mean +/- standard deviation
      (s.d.) 77 +/- 10%]. It correlated positively with body mass index, waist
      circumference, subcutaneous and visceral fat masses and 8-year diabetes risk
      based on the Framingham risk score and inversely with HDL cholesterol and insulin
      sensitivity (M-value; euglycaemic-hyperinsulinaemic clamp). Subcutaneous WAT had
      a significantly higher triglyceride content, 76-95% (mean +/- s.d. 87 +/- 5%; p =
      0.0002). In conclusion, the triglyceride content in supraclavicular fat deposits
      measured by (1)H-MRS may be an independent marker of whole-body insulin
      sensitivity, independent of brown adipose tissue metabolic activation.

PMID- 25586672
TI  - Observation of dynamical heterogeneities and their time evolution on the surface
      of an amorphous polymer.
AB  - Although the formation of dynamic heterogeneities in glass-forming materials is
      believed to play an essential role in determining their properties as the glass
      transition is approached, direct imaging of these heterogeneities remains a
      challenge. Here, we report on a direct observation of nanoscale dynamic
      heterogeneities and their time evolution over ~10(3) s on the surface of a glassy
      polymer, polystyrene (PS), using atomic force microscopy with a 1 nm radius tip.
      The length scale of these heterogeneities was measured to be ~2.1 nm and the
      lifetime was determined to be ~10(2) s, in agreement with the length and time
      scales of heterogeneous dynamics reported for bulk polymers around the glass
      transition. These results are consistent with the existence of a very thin liquid
      like layer at the glassy polymer surface. The validity of the method is confirmed
      by comparing the properties of surface dynamics of neat and plasticized films.

PMID- 25586669
TI  - NQO1-induced activation of AMPK contributes to cancer cell death by oxygen
      glucose deprivation.
AB  - Oxygen and glucose deprivation (OGD) due to insufficient blood circulation can
      decrease cancer cell survival and proliferation in solid tumors. OGD increases
      the intracellular [AMP]/[ATP] ratio, thereby activating the AMPK. In this study,
      we have investigated the involvement of NQO1 in OGD-mediated AMPK activation and
      cancer cell death. We found that OGD activates AMPK in an NQO1-dependent manner,
      suppressing the mTOR/S6K/4E-BP1 pathway, which is known to control cell survival.
      Thus, the depletion of NQO1 prevents AMPK-induced cancer cell death in OGD. When
      we blocked OGD-induced Ca(2+)/CaMKII signaling, the NQO1-induced activation of
      AMPK was attenuated. In addition, when we blocked the RyR signaling, the
      accumulation of intracellular Ca(2+) and subsequent activation of CaMKII/AMPK
      signaling was decreased in NQO1-expressing cells under OGD. Finally, siRNA
      mediated knockdown of CD38 abrogated the OGD-induced activation of
      Ca(2+)/CaMKII/AMPK signaling. Taken together, we conclude that NQO1 plays a key
      role in the AMPK-induced cancer cell death in OGD through the
      CD38/cADPR/RyR/Ca(2+)/CaMKII signaling pathway. 

PMID- 25586671
TI  - Update on the role of angiotensin in the pathophysiology of coronary
      atherothrombosis.
AB  - BACKGROUND: Coronary atherothrombosis due to atherosclerotic plaque rupture or
      erosion is frequently associated with acute coronary syndromes (ACS). Significant
      efforts have been made to elucidate the pathophysiological mechanisms underlying
      acute coronary events. MATERIALS AND METHODS: This narrative review is based on
      the material searched for and obtained via PubMed up to August 2014. The search
      terms we used were as follows: 'angiotensin, acute coronary syndromes, acute
      myocardial infarction' in combination with 'atherosclerosis, vulnerability,
      clinical trial, ACE inhibitors, inflammation'. RESULTS: Among several regulatory
      components, the renin-angiotensin system (RAS) was shown as a key pathway
      modulating coronary atherosclerotic plaque vulnerability. Indeed, these molecules
      are involved in all stages of atherogenesis. Classically, the RAS is composed by
      a series of enzymatic reactions leading to the angiotensin (Ang) II generation
      and activity. However, the knowledge of RAS has expanded and become more complex.
      The discovery of novel components and their functions has revealed additional
      pathways that contribute to or counterbalance the actions of Ang II. In this
      review, we discussed on recent findings concerning the role of different
      angiotensin peptides in the pathophysiology of ACS and coronary atherothrombosis,
      exploring the link between these molecules and atherosclerotic plaque
      vulnerability. CONCLUSIONS: Treatments selectively targeting angiotensins
      (including Mas and AT2 agonists, ACE2 recombinant, or Ang-(1-7) and almandine in
      oral formulations) have been tested in animal studies or in small human
      subgroups, expanding the perspective in the ACS prevention. These novel
      strategies, especially in the counter-regulatory axis ACE2/Ang-(1-7)/Mas, might
      be promising to reduce plaque vulnerability and inflammation.

PMID- 25586673
TI  - Atlanto-axial malformation and instability in dogs with pituitary dwarfism due to
      an LHX3 mutation.
AB  - BACKGROUND: Canine pituitary dwarfism or combined pituitary hormone deficiency
      (CPHD) in shepherd dogs is associated with an LHX3 mutation and can lead to a
      wide range of clinical manifestations. Some dogs with CPHD have neurological
      signs that are localized to the cervical spine. In human CPHD, caused by an LHX3
      mutation, anatomical abnormalities in the atlanto-axial (C1-C2) joint have been
      described. OBJECTIVES: To evaluate the presence of atlanto-axial malformations in
      dogs with pituitary dwarfism associated with an LHX3 mutation and to investigate
      the degree of similarity between the atlanto-axial anomalies found in canine and
      human CPHD patients with an LHX3 mutation. ANIMALS: Three client-owned
      Czechoslovakian wolfdogs and 1 client-owned German shepherd dog, previously
      diagnosed with pituitary dwarfism caused by an LHX3 mutation, with neurological
      signs indicating a cervical spinal disorder. METHODS: Radiography, computed
      tomography, and magnetic resonance imaging of the cranial neck and skull,
      necropsy, and histology. RESULTS: Diagnostic imaging identified abnormal
      positioning of the dens axis and incomplete ossification of the suture lines
      between the ossification centers of the atlas with concurrent atlanto-axial
      instability and dynamic compression of the spinal cord by the dens axis. The
      malformations and aberrant motion at C1-C2 were confirmed at necropsy and
      histology. CONCLUSIONS AND CLINICAL IMPORTANCE: The atlanto-axial abnormalities
      of the dwarf dogs resemble those encountered in human CPHD patients with an LHX3
      mutation. These findings suggest an association between the LHX3 mutation in dogs
      with CPHD and atlanto-axial malformations. Consequently, pituitary dwarfs should
      be monitored closely for neurological signs.

PMID- 25586674
TI  - Profile of plasma amino acids values as a predictor of sepsis in patients
      following living donor liver transplantation: Special reference to sarcopenia and
      postoperative early nutrition.
AB  - AIM: Sarcopenia is an independent predictor of mortality and sepsis after living
      donor liver transplantation (LDLT). However, the exact mechanisms by which
      sarcopenia affects poor prognosis or worse immunity against postoperative sepsis
      are unclear, particularly regarding muscular amino acid metabolism, and the
      authors aimed to identify the role of plasma amino acids in sarcopenia by
      retrospective study. METHODS: The area of the psoas muscle in 228 recipients of
      LDLT was retrospectively measured by dynamic computed tomography. Additionally,
      plasma amino acid levels were measured both pre- and postoperatively. The impact
      of plasma amino acids for postoperative sepsis and the relationship between
      sarcopenia and early nutrition after LDLT were analyzed. RESULTS: Among the
      plasma amino acids, only leucine, isoleucine and glutamine in patients with
      sarcopenia were significantly lower than those without sarcopenia (each, P <
      0.05). Multivariate analysis identified the lower plasma glutamine levels as a
      risk factor of postoperative sepsis after LDLT (odds ratio 5.371, P = 0.002). In
      sarcopenia patients, plasma glutamine levels after LDLT were significantly
      decreased compared with before LDLT in patients both with and without
      postoperative early nutrition. However, in non-sarcopenia patients with early
      nutrition, plasma glutamine levels after LDLT were comparable with those before
      LDLT. CONCLUSION: This is the first report to study the profile of plasma amino
      acid change before and after LDLT. Low preoperative glutamine values were an
      independent risk factor for predicting postoperative sepsis. The efficacy of
      postoperative early nutrition may prevent postoperative sepsis by improving
      glutamine levels.

PMID- 25586675
TI  - Surface-modified Epirubicin-HCl liposomes and its in vitro assessment in breast
      cancer cell-line: MCF-7.
AB  - BACKGROUND: Epirubicin-HCl is highly efficient for breast cancer management at a
      concentration of 60-90 mg/m(2). However, its application is limited due to
      cumulative dose-dependent cardio-toxicity. PURPOSE: The main aim of this study
      was to formulate breast cancer-targeted liposomal carrier by surface conjugation
      of transferrin to minimize cardio-toxicity of drug along with improved
      pharmacokinetic profile. METHOD: Liposomes were formulated by ethanol injection
      method using HSPC, cholesterol and DSPG and later loaded with drug by the
      ammonium sulfate gradient method. The formulation was characterized for
      physicochemical properties like size, zeta potential, entrapment efficiency, TEM;
      in vitro tests like electro-flocculation, hemolysis and drug release; cell line
      study (MCF-7 cells); in vivo studies including LD50 determination,
      pharmacokinetic analysis, myocardial toxicity determination and stability.
      RESULTS AND DISCUSSION: Optimized formulation had molar ratio of 60:30:8:2
      (HSPC:Chol:DSPG:mPEG-DSPE) with entrapment efficiency ~83%, particle size below
      200 nm and zeta potential about -20 mV. In vitro studies proved non-interfering
      property and drug release character of formulation while cell line studies
      demonstrated improvement in cell uptake and thereby increased cytotoxicity of
      targeted formulation. The IC50 value obtained for epirubicin solution, non
      targeted and targeted liposomes was 0.675, 0.532 and 0.192 ug/ml, respectively.
      Furthermore, in vivo tests validated safety and distribution profile of prepared
      formulations. CONCLUSION: Apt properties of prepared Epirubicin-HCl liposomal
      formulation warrant its clinical application in breast cancer treatment after
      further studies.

PMID- 25586676
TI  - Structural characterization of MG and pre-MG states of proteins by MD
      simulations, NMR, and other techniques.
AB  - Almost all proteins fold via a number of partially structured intermediates such
      as molten globule (MG) and pre-molten globule states. Understanding the structure
      of these intermediates at atomic level is often a challenge, as these states are
      observed under extreme conditions of pH, temperature, and chemical denaturants.
      Furthermore, several other processes such as chemical modification, site-directed
      mutagenesis (or point mutation), and cleavage of covalent bond of natural
      proteins often lead to MG like partially unfolded conformation. However, the
      dynamic nature of proteins in these states makes them unsuitable for most
      structure determination at atomic level. Intermediate states studied so far have
      been characterized mostly by circular dichroism, fluorescence, viscosity, dynamic
      light scattering measurements, dye binding, infrared techniques, molecular
      dynamics simulations, etc. There is a limited amount of structural data available
      on these intermediate states by nuclear magnetic resonance (NMR) and hence there
      is a need to characterize these states at the molecular level. In this review, we
      present characterization of equilibrium intermediates by biophysical techniques
      with special reference to NMR. 

PMID- 25586677
TI  - Postpartum consultations in Australian general practice.
AB  - Many GPs undertake postpartum care for women and their infants. GP follow-up
      enables early identification and management of problems, education and support
      for parenting, and reconnection with general practice following the birth.
      However, there is little information about GPs' understanding of their role in
      postpartum care and how it is undertaken. This cross-sectional survey of GPs in
      Southern Queensland, conducted between February and July 2013, describes the
      involvement of GPs in postpartum care. GPs were posted a 52-item questionnaire
      adapted from a previous Victorian GP study and were telephoned 2 weeks later. GPs
      completed the survey on paper or online. The response rate was 17.4% (163 GPs).
      Approximately 39% were uncertain whether women were happy with the GP-provided
      postpartum care. GPs' recommendations for the timing of postpartum reviews were
      inconsistent within and across birthing sectors and consultations took longer
      than anticipated. Developing guidelines around the timing and appropriate length
      of postpartum consultations could assist GPs in providing appropriate care for
      mothers and infants.

PMID- 25586678
TI  - Voxel-based dose calculation in radiocolloid therapy of cystic
      craniopharyngiomas.
AB  - Very high doses are administered in radiocolloid therapy of cystic
      craniopharyngiomas. However individual dose planning is not common yet mainly due
      to insufficient image resolution. Our aim was to investigate whether currently
      available high-resolution image data can be used for voxel-based dose calculation
      for short-ranged beta-emitters ((32)P,(90)Y,(186)Re) and to assess the achievable
      accuracy. We developed a convolution algorithm based on voxelized dose activity
      distributions and dose-spread kernels. Results for targets with 5-40 mm diameter
      were compared with high-resolution Monte Carlo calculations in spherical
      phantoms. Voxel size was 0.35 mm. Homogeneous volume and surface activity
      distributions were used. Dose-volume histograms of targets and shell structures
      were compared and gamma index (dose tolerance 5%, distance to agreement 0.35 mm)
      was calculated for dose profiles along the principal axes. For volumetric
      activity distributions 89.3% +/- 11.9% of all points passed the gamma test (mean
      gamma 0.53  +/-  0.16). For surface distributions 33.6% +/- 14.8% of all points
      passed the gamma test (mean gamma 2.01  +/-  0.60). The shift of curves in dose
      volume histograms was -1.7 Gy +/- 7.6 Gy (-4.4 Gy +/- 24.1 Gy for (186)Re) in
      volumetric distributions and 46.3% +/- 32.8% in surface distributions. The
      results show that individual dose planning for radiocolloid therapy of cystic
      craniopharyngiomas based on high-resolution voxelized image data is feasible and
      yields highly accurate results for volumetric activity distributions and
      reasonable dose estimates for surface distributions.

PMID- 25586679
TI  - "Clinical significance of multifocal and multicentric breast cancers and choice
      of surgical treatment: a retrospective study on a series of 1158 cases".
AB  - BACKGROUND: The biological and clinical significance of multifocal and
      multicentric (MF/MC) breast cancers and the choice of appropriate surgical
      treatment for these tumors are still debated. METHODS: 1158 women operated on for
      a stage I-III breast cancer were included in this retrospective study; clinical
      and pathological data were obtained from the institutional database of the
      Department of Oncology of the University of Siena, Italy. The impact of MF/MC
      breast cancers on patterns of recurrence and breast cancer specific survival
      (BCSS) was investigated in relation to the type of surgical treatment. RESULTS:
      MF and MC cancers were present in 131 cases (11.3%) and 60 cases (5.2%)
      respectively and were more frequently treated with mastectomy (55 MF and 60 MC
      cancers, 81.2%) than with breast conserving surgery (36 MF cancers, 18.9%; p <
      0.001). MF and MC breast cancers were associated with a worse prognosis with a
      BCSS of 154 months compared to 204 months of unicentric cancers (p < 0.001). In
      multivariate analysis, MF/MC cancers were independent prognostic factors for BCSS
      together with higher number of metastatic axillary nodes, absence of estrogen
      receptors and high proliferative activity. MF and MC cancers were related to a
      significantly shorter BCSS in patients submitted to mastectomy as well as those
      submitted to breast conserving surgery. Relapse at any site was higher in the
      subgroup of MF and MC cancers but the incidence of loco-regional and distant
      recurrences did not differ between patients treated with mastectomy or breast
      conserving surgery. CONCLUSIONS: Our results indicate that MF/MC cancers have a
      negative impact on prognosis and are related to higher loregional and distant
      relapse independently from the type of surgery performed. Adjuvant therapies did
      not modify the poorer outcome, but in patients receiving adjuvant anthacyclines,
      the differences with unicentric tumors were reduced. Our data support the
      hypothesis that MF/MC tumors may have a worse biological behavior and that the
      presence of multiple foci should be considered in planning adjuvant treatments.

PMID- 25586680
TI  - Mathematical analysis predicts imbalanced IDH1/2 expression associates with 2-HG
      inactivating beta-oxygenation pathway in colorectal cancer.
AB  - Bioinformatics and computational modeling offer innovative approaches to
      investigate cancer metabolism and predict the secondary and tertiary cellular
      responses. Dysregulation of metabolism has also been implicated in the
      pathophysiology of cancer. A significant proportion of patients with glioblastoma
      and hematological malignancies harbor the mutated forms of the oxidative
      phosphorylation (OxPhos) enzymes, isocitrate dehydrogenase (IDH) 1 or 2. The
      mutated forms of IDH1 and IDH2 produce an oncogenic metabolite, D-2
      hydroxyglutarate (D2HG). A recent study of breast cancer patients showed that
      D2HG can also be produced in the absence of mutated IDH, through an alternative
      route involving over-activated MYC signaling. We developed a novel methodology to
      computationally analyze gene expression in colorectal cancer (CRC), and
      identified novel sets of genes that are associated with patient survival. The
      study of OxPhos-related genes revealed that an imbalance between the expression
      of IDH1 and IDH2, defined as overexpression of one isoform in relation to the
      other, was associated with worse prognosis in CRC patients. This effect was
      further accentuated by reduced expression of the beta-oxygenation enzyme, 3-D
      hydroxyacyl-CoA dehydratase (HCDH) 4, which has been reported to contribute to
      metabolism of intracellular D2HG. The present computational analysis revealed a
      novel and potential mechanism of CRC development, through over-production of D2HG
      when there is an imbalance between IDH1 and IDH2 expression, resulting in
      decreased clearance of D2HG when the beta-oxidization pathway is diminished.
      Additional validation analysis with another gene expression dataset resulted in
      IDH1/2 imbalanced expression with a shorter DFS compared with balanced
      expression. Altogether, these findings provide a strong rationale for studying
      this mechanism further in order to discover novel therapeutic targets for the
      treatment of CRC. 

PMID- 25586681
TI  - Carbapenem therapy is associated with improved survival compared with
      piperacillin-tazobactam for patients with extended-spectrum beta-lactamase
      bacteremia.
AB  - BACKGROUND: The effectiveness of piperacillin-tazobactam (PTZ) for the treatment
      of extended-spectrum beta-lactamase (ESBL) bacteremia is controversial. We
      compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of
      patients with ESBL bacteremia who all received definitive therapy with a
      carbapenem. METHODS: Patients hospitalized between January 2007 and April 2014
      with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling
      dilutions in the minimum inhibitory concentration for third-generation
      cephalosporins tested in combination with 4 ug/mL of clavulanic acid was used to
      confirm ESBL status. The primary exposure was empiric therapy, defined as
      antibiotic therapy administered to a patient before ESBL status was known.
      Patients were excluded if they did not receive a carbapenem after ESBL production
      was identified. The primary outcome was time to death from the first day of
      bacteremia. Propensity scores using inverse probability of exposure weighting
      (IPW) were used to estimate the probability that a patient would receive PTZ vs
      carbapenems empirically. We calculated overall hazard ratios for mortality
      censored at 14 days using Cox proportional hazards models on an IPW-adjusted
      cohort. RESULTS: A total of 331 unique patients with ESBL bacteremia were
      identified. One hundred three (48%) patients received PTZ empirically and 110
      (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times
      higher for patients receiving empiric PTZ compared with empiric carbapenem
      therapy (95% confidence interval, 1.07-3.45). CONCLUSIONS: PTZ appears inferior
      to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of
      invasive ESBL infections, early carbapenem therapy should be considered. Our
      findings should not be extended to beta-lactam/beta-lactamase inhibitor
      combinations in development, as limited clinical data are available for these
      agents.

PMID- 25586683
TI  - Additional benefits of GeneXpert MTB/RIF assay for the evaluation of pulmonary
      tuberculosis among inpatients.

PMID- 25586682
TI  - Use of boosted protease inhibitors reduces Kaposi sarcoma incidence among male
      veterans with HIV infection.
AB  - BACKGROUND: Kaposi sarcoma (KS) incidence has decreased since combination
      antiretroviral therapy (cART). However, effects of cART type and duration on KS
      remain difficult to interpret secondary to KS-associated immune reconstitution
      inflammatory syndrome (IRIS). METHODS: We performed a retrospective study of
      Veterans Affairs Human Immunodeficiency Virus Clinical Case Registry data from
      1985 to 2010. We analyzed the relationship between cART regimens and KS using
      multivariable Poisson regression, stratified or adjusted for timing around cART
      initiation. KS was identified by >= 1 inpatient or >= 2 outpatient International
      Classification of Diseases, Ninth Revision codes (176.0-9). Percent of cART on
      specific regimen and total duration on specific regimen were examined. RESULTS:
      There were 341 KS cases among 25 529 HIV-infected male veterans (incidence rate =
      2.02/1000 person-years). Stratified by years after starting cART, every
      additional 10% time on boosted protease inhibitors (BPIs) was associated with
      reduced KS incidence in the third year of cART (incidence rate ratio [IRR] =
      0.79; 95% confidence interval [CI], .69-.90). Months on BPIs was associated with
      lower KS incidence (P = .02). KS incidence was lower at 12-23 (IRR = 0.47; 95%
      CI, .23-.95) and >= 36 (IRR = 0.14; 95% CI, .02-1.00) months on BPIs compared
      with <6 months. Longer duration on other regimens was not associated with
      decreased KS incidence. CONCLUSIONS: Lower KS incidence was observed with longer
      BPI use, after accounting for potential IRIS and other factors. Future research
      should evaluate newer cART regimens and long-term benefits of PI-based cART on KS
      in other cohorts and prospective studies.

PMID- 25586684
TI  - Editorial commentary: Bloodstream infection caused by extended-spectrum beta
      lactamase-producing Gram-negative bacteria: how to define the best treatment
      regimen?

PMID- 25586685
TI  - Reply to Baker and Holtom.

PMID- 25586686
TI  - T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood:
      a clinical trial.
AB  - BACKGROUND: Microbiologic cultures, the current gold standard diagnostic method
      for invasive Candida infections, have low specificity and take up to 2-5 days to
      grow. We present the results of the first extensive multicenter clinical trial of
      a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of
      candidemia. METHODS: Blood specimens were collected from 1801 hospitalized
      patients who had a blood culture ordered for routine standard of care; 250 of
      them were manually supplemented with concentrations from <1 to 100 colony-forming
      units (CFUs)/mL for 5 different Candida species. RESULTS: T2MR demonstrated an
      overall specificity per assay of 99.4% (95% confidence interval [CI], 99.1%
      99.6%) with a mean time to negative result of 4.2 +/- 0.9 hours. Subanalysis
      yielded a specificity of 98.9% (95% CI, 98.3%-99.4%) for Candida albicans/Candida
      tropicalis, 99.3% (95% CI, 98.7%-99.6%) for Candida parapsilosis, and 99.9% (95%
      CI, 99.7%-100.0%) for Candida krusei/Candida glabrata. The overall sensitivity
      was found to be 91.1% (95% CI, 86.9%-94.2%) with a mean time of 4.4 +/- 1.0 hours
      for detection and species identification. The subgroup analysis showed a
      sensitivity of 92.3% (95% CI, 85.4%-96.6%) for C. albicans/C. tropicalis, 94.2%
      (95% CI, 84.1%-98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%-93.7%) for C.
      krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C.
      krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C.
      parapsilosis. The negative predictive value was estimated to range from 99.5% to
      99.0% in a study population with 5% and 10% prevalence of candidemia,
      respectively. CONCLUSIONS: T2MR is the first fully automated technology that
      directly analyzes whole blood specimens to identify species without the need for
      prior isolation of Candida species, and represents a breakthrough shift into a
      new era of molecular diagnostics. CLINICAL TRIALS REGISTRATION: NCT01752166.

PMID- 25586687
TI  - High capsid-genome correlation facilitates creation of AAV libraries for directed
      evolution.
AB  - Directed evolution of adeno-associated virus (AAV) through successive rounds of
      phenotypic selection is a powerful method to isolate variants with improved
      properties from large libraries of capsid mutants. Importantly, AAV libraries
      used for directed evolution are based on the "natural" AAV genome organization
      where the capsid proteins are encoded in cis from replicating genomes. This is
      necessary to allow the recovery of the capsid DNA after each step of phenotypic
      selection. For directed evolution to be used successfully, it is essential to
      minimize the random mixing of capsomers and the encapsidation of nonmatching
      viral genomes during the production of the viral libraries. Here, we demonstrate
      that multiple AAV capsid variants expressed from Rep/Cap containing viral genomes
      result in near-homogeneous capsids that display an unexpectedly high capsid-DNA
      correlation. Next-generation sequencing of AAV progeny generated by bulk
      transfection of a semi-random peptide library showed a strong counter-selection
      of capsid variants encoding premature stop codons, which further supports a
      strong capsid-genome identity correlation. Overall, our observations demonstrate
      that production of "natural" AAVs results in low capsid mosaicism and high capsid
      genome correlation. These unique properties allow the production of highly
      diverse AAV libraries in a one-step procedure with a minimal loss in phenotype
      genotype correlation. 

PMID- 25586690
TI  - Anaphylaxis attributed to exercise: considerations for sports medicine
      specialists.
AB  - Anaphylaxis is an unanticipated, acute, and sometimes life-threatening systemic
      reaction with variable clinical presentations that is typically mediated by
      immunoglobulin E and causes degranulation of mast cells and basophils. The onset
      of symptoms can occur within minutes or hours after exposure to a known or
      suspected trigger, and reactions sometimes progress very rapidly, which can lead
      to death. One trigger of anaphylaxis in younger adults is moderately intense
      physical exercise, which has been termed exercise-induced anaphylaxis (EIA).
      Although rare, EIA should be recognized as a distinct and potentially life
      threatening form of physical allergy, and is often undetected or inadequately
      treated. The ingestion of specific foods, including seafood, tree nuts, and
      wheat, or a nonspecific meal consisting of multiple food components shortly
      before or after physical exertion, is sometimes, but not always, the principal
      precipitant of EIA. This article briefly explores the current hypotheses on the
      role of immunoglobulin E, response mediators, and physiologic changes that bring
      on EIA, and discusses the current recommendations for diagnosis, including
      allergen challenge and laboratory testing, emergency care, and long-term
      prevention and patient follow-up. Accurate diagnosis of EIA is critical to
      providing lifesaving therapy and care plans to patients at risk. With respect to
      the medical management of EIA, mainstay therapy with epinephrine is described.
      For those with a known history of EIA, a comprehensive anaphylaxis action plan is
      central to successful patient management. Furthermore, patient education is
      necessary to heighten awareness of the signs and symptoms of EIA and appropriate
      strategies for allergen avoidance and self-management of anaphylactic episodes
      with self-injectable epinephrine.

PMID- 25586688
TI  - Intra-amniotic rAAV-mediated microdystrophin gene transfer improves canine X
      linked muscular dystrophy and may induce immune tolerance.
AB  - Duchenne muscular dystrophy (DMD) is a severe congenital disease due to mutations
      in the dystrophin gene. Supplementation of dystrophin using recombinant
      adenoassociated virus vector has promise as a treatment of DMD, although
      therapeutic benefit of the truncated dystrophin still remains to be elucidated.
      Besides, host immune responses against the vector as well as transgene products
      have been denoted in the clinical gene therapy studies. Here, we transduced
      dystrophic dogs fetuses to investigate the therapeutic effects of an AAV vector
      expressing microdystrophin under conditions of immune tolerance. rAAV-CMV
      microdystrophin and a rAAV-CAG-luciferase were injected into the amniotic fluid
      surrounding fetuses. We also reinjected rAAV9-CMV-microdystrophin into the
      jugular vein of an infant dystrophic dog to induce systemic expression of
      microdystrophin. Gait and cardiac function significantly improved in the rAAV
      microdystrophin-injected dystrophic dog, suggesting that an adequate treatment of
      rAAV-microdystrophin with immune modulation induces successful long-term
      transgene expression to analyze improved dystrophic phenotype. 

PMID- 25586689
TI  - First-in-man phase 1 clinical trial of gene therapy for advanced pancreatic
      cancer: safety, biodistribution, and preliminary clinical findings.
AB  - This phase 1 trial was aimed to determine the safety, pharmacokinetics, and
      preliminary clinical activity of CYL-02, a nonviral gene therapy product that
      sensitizes pancreatic cancer cells to chemotherapy. CYL-02 was administrated
      using endoscopic ultrasound in 22 patients with pancreatic cancer that
      concomitantly received chemotherapy (gemcitabine). The maximum-tolerated dose
      (MTD) exceeded the maximal feasible dose of CYL-02 and was not identified.
      Treatment-related toxicities were mild, without serious adverse events.
      Pharmacokinetic analysis revealed a dose-dependent increase in CYL-02 DNA
      exposure in blood and tumors, while therapeutic RNAs were detected in tumors. No
      objective response was observed, but nine patients showed stable disease up to 6
      months following treatment and two of these patients experienced long-term
      survival. Panels of plasmatic microRNAs and proteins were identified as
      predictive of gene therapy efficacy. We demonstrate that CYL-02 nonviral gene
      therapy has a favorable safety profile and is well tolerated in patients. We
      characterize CYL-02 biodistribution and demonstrate therapeutic gene expression
      in tumors. Treated patients experienced stability of disease and predictive
      biomarkers of response to treatment were identified. These promising results
      warrant further evaluation in phase 2 clinical trial. 

PMID- 25586692
TI  - Atypical urothelial tissue fragments in noninstrumented voided urine specimens
      are associated with low but significantly higher rates of urothelial neoplasia
      than benign-appearing urothelial tissue fragments.
AB  - BACKGROUND: The interpretation of urothelial tissue fragments (UTF) in voided
      urine (VU) specimens is controversial. If UTF contain cytomorphologically
      atypical cells, the diagnosis often becomes more challenging. The authors
      previously analyzed the outcome of patients with benign-appearing UTF in 274
      noninstrumented VU specimens. In this retrospective study, noninstrumented VU
      specimens containing UTF with atypical cytomorphological features (AUTF) were
      evaluated and compared with the previous results. METHODS: The Johns Hopkins
      Hospital electronic pathology database was searched for VU cases containing UTF
      over a 5-year period. RESULTS: A total of 170 noninstrumented VU specimens
      containing AUTF were identified. Twenty-four specimens had subsequent or
      coincidental surgical pathology specimens with the following overall rates of
      neoplasia: high-grade urothelial carcinoma: 8.8% (15 specimens), low-grade
      urothelial neoplasia: 1.2% (2 specimens), and prostate carcinoma invading the
      bladder: 0.6% (1 specimen). A total of 49 specimens (28.8%) were diagnosed with
      urolithiasis on follow-up. Twenty-five cases had follow-up cytology specimens,
      all of which were negative for malignancy. Of 72 cases without histopathologic,
      radiologic, or cytopathologic follow-up, 62 (86.1%) had a mean clinical follow-up
      of 22.5 months and 10 cases did not have clinical follow-up. CONCLUSIONS: The
      presence of AUTF in noninstrumented VU is associated with low rates of urothelial
      neoplasia but a statistically higher risk of urothelial neoplasia than the
      presence of BUTF (10.0% vs 4.4%; P<.05). In particular, the rate of high-grade
      urothelial carcinoma is significantly higher in noninstrumented VU specimens
      containing AUTF than those containing BUTF (8.8% vs 0.7%; P<.0001). In addition,
      urolithiasis is associated with AUTF in a substantial percentage of
      noninstrumented VU specimens.

PMID- 25586691
TI  - Intrinsic cancer subtypes--next steps into personalized medicine.
AB  - Recent technological advances have significantly improved our understanding of
      tumor biology by means of high-throughput mutation and transcriptome analyses.
      The application of genomics has revealed the mutational landscape and the
      specific deregulated pathways in different tumor types. At a transcriptional
      level, multiple gene expression signatures have been developed to identify
      biologically distinct subgroups of tumors. By supervised analysis, several
      prognostic signatures have been generated, some of them being commercially
      available. However, an unsupervised approach is required to discover a priori
      unknown molecular subtypes, the so-called intrinsic subtypes. Moreover, an
      integrative analysis of the molecular events associated with tumor biology has
      been translated into a better tumor classification. This molecular
      characterization confers new opportunities for therapeutic strategies in the
      management of cancer patients. However, the applicability of these new molecular
      classifications is limited because of several issues such as technological
      validation and cost. Further comparison with well-established clinical and
      pathological features is expected to accelerate clinical translation. In this
      review, we will focus on the data reported on molecular classification in the
      most common tumor types such as breast, colorectal and lung carcinoma, with
      special emphasis on recent data regarding tumor intrinsic subtypes. Likewise, we
      will review the potential applicability of these new classifications in the
      clinical routine.

PMID- 25586693
TI  - Congenital absence of the left atrial appendage visualized by 3D echocardiography
      in two adult patients.
AB  - Congenital absence of left atrial appendage (LAA) is an extremely rare condition
      and its physiological consequences are unknown. We present two cases of
      incidental finding of a congenitally absent LAA in a 79-year-old male who
      presented for routine transesophageal echocardiogram (TEE) to rule out
      intracardiac thrombus prior to placement of biventricular implantable
      cardioverter-defibrillator and a 54-year old female who presented for TEE prior
      to radiofrequency ablation of atrial fibrillation. Characterization of patients
      with such an absence is important because congenitally absent LAA may be confused
      with flush thrombotic occlusion of the appendage. There are very few published
      reports of congenital absence of LAA. To our knowledge, our report is the first
      to demonstrate the congenital absence of LAA by 3D transesophageal
      echocardiography. 

PMID- 25586696
TI  - A rare case of first motor branch of median nerve schwannoma.

PMID- 25586697
TI  - BioMEMS and Lab-on-a-Chip Course Education at West Virginia University.
AB  - With the rapid growth of Biological/Biomedical MicroElectroMechanical Systems
      (BioMEMS) and microfluidic-based lab-on-a-chip (LOC) technology to biological and
      biomedical research and applications, demands for educated and trained
      researchers and technicians in these fields are rapidly expanding. Universities
      are expected to develop educational plans to address these specialized needs in
      BioMEMS, microfluidic and LOC science and technology. A course entitled BioMEMS
      and Lab-on-a-Chip was taught recently at the senior undergraduate and graduate
      levels in the Department of Computer Science and Electrical Engineering at West
      Virginia University (WVU). The course focused on the basic principles and
      applications of BioMEMS and LOC technology to the areas of biomedicine, biology,
      and biotechnology. The course was well received and the enrolled students had
      diverse backgrounds in electrical engineering, material science, biology,
      mechanical engineering, and chemistry. Student feedback and a review of the
      course evaluations indicated that the course was effective in achieving its
      objectives. Student presentations at the end of the course were a highlight and a
      valuable experience for all involved. The course proved successful and will
      continue to be offered regularly. This paper provides an overview of the course
      as well as some development and future improvements. 

PMID- 25586695
TI  - Hypomelanosis of Ito: a round on the frequency and type of epileptic
      complications.
AB  - There is an ample evidence that hypopigmentation of the skin along the Blaschko's
      lines is frequently associated with neurological disorders. Nowadays, the term
      "Hypomelanosis of Ito" (HI) is applied when, together with the cutaneous lesions,
      various and multisystem organs are involved. Among these, the most frequent are
      cerebral manifestations, such as cognitive delay and epileptic seizures. For this
      reason, hypomelanosis of Ito has been included in the group of neurocutaneous
      syndromes, neurologic manifestations being one of the most frequent. Epileptic
      seizures have been reported in patients with this disorder, but in a very few
      particular attention has been focused on the type and frequency of epilepsy and
      on the response to the treatment. Herein, we report on five patients with HI who
      showed episodes of epileptic seizures with onset in childhood, in absence of
      malformative anomalies except for the skin lesions. A survey on the frequency and
      types of epileptic seizures in HI children and in the literature is reported. 

PMID- 25586698
TI  - Nonlinear dielectric spectroscopy as an indirect probe of metabolic activity in
      thylakoid membrane.
AB  - Nonlinear dielectric spectroscopy (NDS) is a non-invasive probe of cellular
      metabolic activity with potential application in the development of whole-cell
      biosensors. However, the mechanism of NDS interaction with metabolic membrane
      proteins is poorly understood, partly due to the inherent complexity of single
      cell organisms. Here we use the light-activated electron transport chain of
      spinach thylakoid membrane as a model system to study how NDS interacts with
      metabolic activity. We find protein modification, as opposed to membrane pump
      activity, to be the dominant source of NDS signal change in this system.
      Potential mechanisms for such protein modifications include reactive oxygen
      species generation and light-activated phosphorylation. 

PMID- 25586699
TI  - Dielectrophoresis Aligned Single-Walled Carbon Nanotubes as pH Sensors.
AB  - Here we report the fabrication and characterization of pH sensors using aligned
      single-walled carbon nanotubes (SWNTs). The SWNTs are dispersed in deionized (DI)
      water after chemical functionalization and filtration. They are deposited and
      organized on silicon substrates with the dielectrophoresis process. Electrodes
      with "teeth"-like patterns-fabricated with photolithography and wet etching-are
      used to generate concentrated electric fields and strong dielectrophoretic forces
      for the SWNTs to deposit and align in desired locations. The device fabrication
      is inexpensive, solution-based, and conducted at room temperature. The devices
      are used as pH sensors with the electrodes as the testing pads and the
      dielectrophoretically captured SWNTs as the sensing elements. When exposed to
      aqueous solutions with various pH values, the SWNTs change their resistance
      accordingly. The SWNT-based sensors demonstrate a linear relationship between the
      sensor resistance and the pH values in the range of 5-9. The characterization of
      multiple sensors proves that their pH sensitivity is highly repeatable. The real
      time data acquisition shows that the sensor response time depends on the pH
      value, ranging from 2.26 s for the pH-5 solution to 23.82 s for the pH-9
      solution. The long-term stability tests illustrate that the sensors can maintain
      their original sensitivity for a long period of time. The simple fabrication
      process, high sensitivity, and fast response of the SWNT-based sensors facilitate
      their applications in a wide range of areas. 

PMID- 25586700
TI  - Environmental osmolality influences sperm motility activation in an anuran
      amphibian.
AB  - Evolutionary theory predicts that selection will favour sperm traits that
      maximize fertilization success in local fertilization environments. In externally
      fertilizing species, osmolality of the fertilization medium is known to play a
      critical role in activating sperm motility, but there remains limited evidence
      for adaptive responses to local osmotic environments. In this study, we used a
      split-sample experimental design and computer-assisted sperm analysis to (i)
      determine the optimal medium osmolality for sperm activation (% sperm motility
      and sperm velocity) in male common eastern froglets (Crinia signifera), (ii) test
      for among-population variation in percentage sperm motility and sperm velocity at
      various activation-medium osmolalities and (iii) test for among-population
      covariation between sperm performance and environmental osmolality. Frogs were
      obtained from nine populations that differed in environmental osmolality, and
      sperm samples of males from different populations were subjected to a range of
      activation-medium osmolalities. Percentage sperm motility was optimal between 10
      and 50 mOsm kg(-1) , and sperm velocity was optimal between 10 and 100 mOsm kg(
      1) , indicating that C. signifera has evolved sperm that can function across a
      broad range of osmolalities. As predicted, there was significant among-population
      variation in sperm performance. Furthermore, there was a significant interaction
      between activation-medium osmolality and environmental osmolality, indicating
      that frogs from populations with higher environmental osmolality produced sperm
      that performed better at higher osmolalities in vitro. This finding may reflect
      phenotypic plasticity in sperm functioning, or genetic divergence resulting from
      spatial variation in the strength of directional selection. Both of these
      explanations are consistent with evolutionary theory, providing some of the first
      empirical evidence that local osmotic environments can favour adaptive sperm
      motility responses in species that use an external mode of fertilization.

PMID- 25586701
TI  - Two Multiple Sclerosis Quality-of-Life Measures: Comparison in a National Sample.
AB  - BACKGROUND: Multiple sclerosis (MS) has a profound impact on patients' health
      related quality of life (HRQoL). It is unclear how HRQoL can be best assessed for
      different purposes. This study aimed to compare two HRQoL questionnaires of
      differing lengths for feasibility of administration, patient perceptions and
      psychometric properties. METHODS: This was an open-label, 24-month study in 334
      patients with relapsing MS treated with subcutaneous interferon beta-1a. At
      baseline and months 6, 12, 18 and 24, patients completed the Multiple Sclerosis
      International Quality of Life (MusiQoL) and Multiple Sclerosis Quality of Life-54
      (MSQOL-54) questionnaires and compared them using an evaluation questionnaire.
      HRQoL scores over time and psychometric properties (correlations with clinical
      disease measures, relative validity and responsiveness to change) of the
      questionnaires were assessed. RESULTS: A minority of patients had missing items
      on either HRQoL measure. Completion time was significantly shorter for MusiQoL
      versus MSQOL-54 (p<0.0001). Patients felt that MusiQoL was easier to use than
      MSQOL-54 but preferred MSQOL-54 in terms of thoroughness. Mean HRQoL scores
      increased significantly from baseline to 24 months; correlations of both measures
      were stronger with an anxiety and depression measure than with disability or
      recent relapse occurrence. Relative validity and responsiveness to change were
      similar for both instruments. CONCLUSION: The shorter MusiQoL is suitable for
      evaluating HRQoL in patients with MS and may be more practical to administer than
      the more thorough MSQOL-54.

PMID- 25586702
TI  - Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and
      Plasmodium falciparum.
AB  - Intercellular adhesion molecules (ICAMs) belong to the immunoglobulin superfamily
      and participate in diverse cellular processes including host-pathogen
      interactions. ICAM-1 is expressed on various cell types including macrophages,
      whereas ICAM-4 is restricted to red blood cells. Here we report the
      identification of an 11-kDa synthetic protein, M5, that binds to human ICAM-1 and
      ICAM-4, as shown by in vitro interaction studies, surface plasmon resonance and
      immunolocalization. M5 greatly inhibits the invasion of macrophages and
      erythrocytes by Mycobacterium tuberculosis and Plasmodium falciparum,
      respectively. Pharmacological and siRNA-mediated inhibition of ICAM-1 expression
      also results in reduced M. tuberculosis invasion of macrophages. ICAM-4 binds to
      P. falciparum merozoites, and the addition of recombinant ICAM-4 to parasite
      cultures blocks invasion of erythrocytes by newly released merozoites. Our
      results indicate that ICAM-1 and ICAM-4 play roles in host cell invasion by M.
      tuberculosis and P. falciparum, respectively, either as receptors or as crucial
      accessory molecules. 

PMID- 25586703
TI  - An aqueous method for the controlled manganese (Mn(2+)) substitution in
      superparamagnetic iron oxide nanoparticles for contrast enhancement in MRI.
AB  - Despite the success in the use of superparamagnetic iron oxide nanoparticles
      (SPION) for various scientific applications, its potential in biomedical fields
      has not been exploited to its full potential. In this context, an in situ
      substitution of Mn(2+) was performed in SPION and a series of ferrite particles,
      MnxFe1-xFe2O4 with a varying molar ratio of Mn(2+) : Fe(2+) where 'x' varies from
      0-0.75. The ferrite particles obtained were further studied in MRI contrast
      applications and showed appreciable enhancement in their MRI contrast properties.
      Manganese substituted ferrite nanocrystals (MnIOs) were synthesized using a
      novel, one-step aqueous co-precipitation method based on the use of a combination
      of sodium hydroxide and trisodium citrate (TSC). This approach yielded the
      formation of highly crystalline, superparamagnetic MnIOs with good control over
      their size and bivalent Mn ion crystal substitution. The presence of a TSC
      hydrophilic layer on the surface facilitated easy dispersion of the materials in
      an aqueous media. Primary characterizations such as structural, chemical and
      magnetic properties demonstrated the successful formation of manganese
      substituted ferrite. More significantly, the MRI relaxivity of the MnIOs improved
      fourfold when compared to SPION crystals imparting high potential for use as an
      MRI contrast agent. Further, the cytocompatibility and blood compatibility
      evaluations demonstrated excellent cell morphological integrity even at high
      concentrations of nanoparticles supporting the non-toxic nature of nanoparticles.
      These results open new horizons for the design of biocompatible water dispersible
      ferrite nanoparticles with good relaxivity properties via a versatile and easily
      scalable co-precipitation route. 

PMID- 25586704
TI  - Dual-tip magnetic force microscopy with suppressed influence on magnetically soft
      samples.
AB  - Standard magnetic force microscopy (MFM) is considered as a powerful tool used
      for magnetic field imaging at nanoscale. The method consists of two passes
      realized by the magnetic tip. Within the first one, the topography pass, the
      magnetic tip directly touches the magnetic sample. Such contact perturbs the
      magnetization of the sample explored. To avoid the sample touching the magnetic
      tip, we present a new approach to magnetic field scanning by segregating the
      topological and magnetic scans with two different tips located on a cut
      cantilever. The approach minimizes the disturbance of sample magnetization, which
      could be a major problem in conventional MFM images of soft magnetic samples. By
      cutting the cantilever in half using the focused ion beam technique, we create
      one sensor with two different tips--one tip is magnetized, and the other one is
      left non-magnetized. The non-magnetized tip is used for topography and the
      magnetized one for the magnetic field imaging. The method developed we call dual
      tip magnetic force microscopy (DT-MFM). We describe in detail the dual-tip
      fabrication process. In the experiments, we show that the DT-MFM method reduces
      significantly the perturbations of the magnetic tip as compared to the standard
      MFM method. The present technique can be used to investigate microscopic magnetic
      domain structures in a variety of magnetic samples and is relevant in a wide
      range of applications, e.g., data storage and biomedicine.

PMID- 25586705
TI  - In vitro comparison of biological and synthetic materials for skeletal chest wall
      reconstruction.
AB  - BACKGROUND: Various biological and synthetic materials have been proposed for use
      in skeletal chest wall reconstruction (SCWR). Because of the lack of studies
      allowing a direct comparison of SCWR materials, their clinical use often depends
      on the surgeon's preference and experience. The aim of this study was to analyze
      6 synthetic and 3 biological materials frequently used in SCWR with respect to
      their cytotoxicity, bacterial adhesion, surface characteristics, and mechanical
      properties to facilitate data-driven decisions. METHODS: The effect of the SCWR
      materials and their extracts on the metabolism of human skeletal muscle cells
      (SkMCs), dermal fibroblasts, adipose cells, and osteoblasts was analyzed in
      vitro. Bacterial adhesion was quantified by incubating samples in bacterial
      suspensions (Staphylococcus epidermidis, S aureus, and Escherichia coli),
      followed by counting colony-forming units and performing scanning electron
      microscopy. Moreover, the mechanical properties of the materials were analyzed
      under uniaxial tensile loading to failure. RESULTS: The metabolism of all cell
      types seeded on the SCWR materials was reduced compared with untreated cells.
      With the exception of Vypro (Ethicon, Somerville, NJ), whose extracts
      significantly reduced fibroblast viability, no cytotoxic leachable substances
      were detected. Biological materials were less cytotoxic compared with synthetic
      ones, but they demonstrated increased bacterial adhesion. Synthetic materials
      demonstrated higher elongation to failure than did biological materials.
      CONCLUSIONS: Biological and synthetic SCWR materials showed significant
      differences in their cytotoxicity, bacterial adhesion, and biomechanical
      properties, suggesting that they may be used for different indications in SCWR.
      Further comparable in vivo studies are needed to analyze their performance in
      different indications of clinical application.

PMID- 25586706
TI  - Incidence and mechanisms of cerebral ischemia after transcatheter aortic valve
      implantation compared with surgical aortic valve replacement.
AB  - BACKGROUND: The most likely mechanisms of neurologic injury after transcatheter
      aortic valve implantation (TAVI) and aortic valve replacement (AVR) are cerebral
      embolization and hypoperfusion. We set out to determine potential mechanisms of
      neurologic injury after TAVI compared with AVR. METHODS: One hundred twenty-seven
      consecutive high-risk patients with severe aortic stenosis (AS) who underwent
      TAVI (n = 85) or AVR (n = 42) were studied. Transcranial Doppler ultrasound
      (TCD), cerebral oximetry, diffusion-weighted magnetic resonance imaging (DW-MRI)
      (before, 6 days, and 3 months after procedure), and neurocognitive assessment
      before and at 3 months were performed. RESULTS: Neurologic injury was not
      significantly different between TAVI and AVR at 1 (1.1% vs 2.2%, p = 0.25) and 3
      months (4.7% vs 2.2%, p = 1). At 3 months, overall cognitive score was higher in
      AVR compared with TAVI when adjusted for baseline score; the estimated difference
      between groups was 0.63 (95% confidence interval 0.87% to 1.17%; p = 0.02).
      Cerebral embolic load was 212 (123 to 344) during AVR and 134 (76 to 244) during
      TAVI (p = 0.07). Cerebral oxygen desaturation during AVR (7.56 +/- 2.16) was
      higher compared with TAVI (5.93 +/- 2.47) (p < 0.01). Ischemic lesions measured
      by DW-MRI occurred in 76% of TAVI and 71% of AVR patients at 6 days (p = 0.69)
      and 63% and 39% at 3 months (p = 0.11). No significant association was found
      between cerebral emboli, cerebral oxygen desaturation, brain ischemic lesions,
      and general cognitive score. CONCLUSIONS: At 3 months follow-up, overall
      cognitive score was higher in AVR compared with TAVI, adjusted for baseline
      score. However, there was no difference in cerebral embolic load, ischemic
      lesions, and oxygen desaturation.

PMID- 25586707
TI  - Effect of macroscale formation of intraluminal thrombus on blood flow in
      abdominal aortic aneurysms.
AB  - A mathematical approach of blood flow within an abdominal aortic aneurysm (AAA)
      with intraluminal thrombus (ILT) is presented. The macroscale formation of ILT is
      modeled as a growing porous medium with variable porosity and permeability
      according to values proposed in the literature. The model outlines the effect of
      a porous ILT on blood flow in AAAs. The numerical solution is obtained by
      employing a structured computational mesh of an idealized fusiform AAA geometry
      and applying the Galerkin weighted residual method in generalized curvilinear
      coordinates. Results on velocity and pressure fields of independent cases with
      and without ILT are presented and discussed. The vortices that develop within the
      aneurysmal cavity are studied and visualized as ILT becomes more condensed. From
      a mechanistic point of view, the reduction of bulge pressure, as ILT is
      thickening, supports the observation that ILT could protect the AAA from a
      possible rupture. The model also predicts a relocation of the maximum pressure
      region toward the zone proximal to the neck of the aneurysm. However, other
      mechanisms, such as the gradual wall weakening that usually accompany AAA and ILT
      formation, which are not included in this study, may offset this effect. 

PMID- 25586708
TI  - Real-time pretreatment review limits unacceptable deviations on a cooperative
      group radiation therapy technique trial: quality assurance results of RTOG 0933.
AB  - PURPOSE: RTOG 0933 was a phase II trial of hippocampal avoidance during whole
      brain radiation therapy for patients with brain metastases. The results
      demonstrated improvement in short-term memory decline, as compared with
      historical control individuals, and preservation of quality of life. Integral to
      the conduct of this trial were quality assurance processes inclusive of pre
      enrollment credentialing and pretreatment centralized review of enrolled
      patients. METHODS AND MATERIALS: Before enrolling patients, all treating
      physicians and sites were required to successfully complete a "dry-run"
      credentialing test. The treating physicians were credentialed based on accuracy
      of magnetic resonance imaging-computed tomography image fusion and hippocampal
      and normal tissue contouring, and the sites were credentialed based on protocol
      specified dosimetric criteria. Using the same criteria, pretreatment centralized
      review of enrolled patients was conducted. Physicians enrolling 3 consecutive
      patients without unacceptable deviations were permitted to enroll further
      patients without pretreatment review, although their cases were reviewed after
      treatment. RESULTS: In all, 113 physicians and 84 sites were credentialed. Eight
      physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were
      approved on the second attempt. Eight sites (9.5%) failed intensity modulated
      radiation therapy planning on the first attempt; all were approved on the second
      attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were
      analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated
      the eligibility criteria, and 21 (24%) had unacceptable deviations. With
      feedback, 18 cases were approved on the second attempt and 2 cases on the third
      attempt. One patient was treated off protocol. Twenty-two cases were reviewed
      after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had
      unacceptable deviations. CONCLUSIONS: Although >95% of the cases passed the pre
      enrollment credentialing, the pretreatment centralized review disqualified 5.7%
      of reviewed cases, prevented unacceptable deviations in 24% of reviewed cases,
      and limited the final unacceptable deviation rate to 5%. Thus, pretreatment
      review is deemed necessary in future hippocampal avoidance trials and is
      potentially useful in other similarly challenging radiation therapy technique
      trials.

PMID- 25586709
TI  - Improved detection of bone metastases from lung cancer in the thoracic cage using
      5- and 1-mm axial images versus a new CT software generating rib unfolding
      images: comparison with standard 18F-FDG-PET/CT.
AB  - RATIONALE AND OBJECTIVES: To evaluate the performance of a dedicated computed
      tomography (CT) software called "bone reading" generating rib unfolded images for
      improved detection of rib metastases in patients with lung cancer in comparison
      to readings of 5- and 1-mm axial CT images and (18)F-Fluordeoxyglucose positron
      emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS:
      Ninety consecutive patients who underwent (18)F-FDG-PET/CT and chest CT scanning
      between 2012 and 2014 at our institution were analyzed retrospectively. Chest CT
      scans with 5- and 1-mm slice thickness were interpreted blindly and separately
      focused on the detection of rib metastases (location, number, cortical vs.
      medullary, and osteoblastic vs. sclerotic). Subsequent image analysis of unfolded
      1 mm-based CT rib images was performed. For all three data sets the reading time
      was registered. Finally, results were compared to those of FDG-PET. Validation
      was based on FDG-PET positivity for osteolytic and mixed osteolytic/osteoblastic
      focal rib lesions and follow-up for sclerotic PET-negative lesions. RESULTS: A
      total of 47 metastatic rib lesions were found on FDG-PET/CT plus another 30
      detected by CT bone reading and confirmed by follow-up CT. Twenty-nine lesions
      were osteolytic, 14 were mixed osteolytic/osteoblastic, and 34 were sclerotic. On
      a patient-based analysis, CT (5 mm), CT (1 mm), and CT (1-mm bone reading)
      yielded a sensitivity, specificity, and accuracy of 76.5/97.3/93, 81.3/97.3/94,
      and 88.2/95.9/92, respectively. On segment-based (unfolded rib) analysis, the
      sensitivity, specificity, and accuracy of the three evaluations were
      47.7/95.7/67, 59.5/95.8/77, and 94.8/88.2/92, respectively. Reading time for 5
      mm/1 mm axial images and unfolded images was 40.5/50.7/21.56 seconds,
      respectively. CONCLUSIONS: The use of unfolded rib images in patients with lung
      cancer improves sensitivity and specificity of rib metastasis detection in
      comparison to 5- and 1-mm CT slice reading. Moreover, it may reduce the reading
      time.

PMID- 25586710
TI  - Intraindividual comparison of two methods of volumetric breast composition
      assessment.
AB  - RATIONALE AND OBJECTIVES: To compare the results of two software-based methods,
      Quantra and Volpara, for volumetric breast composition assessment. MATERIALS AND
      METHODS: Four hundred forty-five normal, bilateral, two-view, digital mammograms
      were included. Breast volume (BV), fibroglandular tissue volume (FTV), and
      percent density (PD) were measured using both methods and compared. Deming
      regression was performed to obtain linear equations for mapping the results of
      one software on the other. RESULTS: The median and quartile ranges of both
      methods agreed well for BV but were different for FTV and PD, with Quantra
      showing much higher values of FTV and PD. The correlation of results obtained by
      both methods for BV, FTV, and PD was 0.99, 0.91, and 0.94, respectively.
      Intraclass correlation in the assignment of quartiles of BV, FTV, and PD was
      0.96, 0.86, and 0.90, respectively. Both methods showed a similar association of
      FTV and PD with patient age and similar left-to-right correlation. Mapping of
      results onto each other using linear equations removed the systematic
      differences. CONCLUSIONS: Although Quantra and Volpara use different models for
      analysis of volumetric breast composition and produce different nominal results
      of FTV and PD, both methods are highly correlated and show very good to excellent
      agreement in quartile assignment of all parameters measured. Both methods show a
      similar association with patient age and similar reproducibility. Both methods
      can be mapped onto each other using the equations suggested.

PMID- 25586711
TI  - The effectiveness of health animations in audiences with different health
      literacy levels: an experimental study.
AB  - BACKGROUND: Processing Web-based health information can be difficult, especially
      for people with low health literacy. Presenting health information in an
      audiovisual format, such as animation, is expected to improve understanding among
      low health literate audiences. OBJECTIVE: The aim of this paper is to investigate
      what features of spoken health animations improve information recall and
      attitudes and whether there are differences between health literacy groups.
      METHODS: We conducted an online experiment among 231 participants aged 55 years
      or older with either low or high health literacy. A 2 (spoken vs written text) x
      2 (illustration vs animation) design was used. Participants were randomly exposed
      to one of the four experimental messages, all providing the same information on
      colorectal cancer screening. RESULTS: The results showed that, among people with
      low health literacy, spoken messages about colorectal cancer screening improved
      recall (P=.03) and attitudes (P=.02) compared to written messages. Animations
      alone did not improve recall, but when combined with spoken text, they
      significantly improved recall in this group (P=.02). When exposed to spoken
      animations, people with low health literacy recalled the same amount of
      information as their high health literate counterparts (P=.12), whereas in all
      other conditions people with high health literacy recalled more information
      compared to low health literate individuals. For people with low health literacy,
      positive attitudes mediated the relationship between spoken text and the
      intention to have a colorectal cancer screening (b=.12; 95% CI 0.02-0.25).
      CONCLUSIONS: We conclude that spoken animation is the best way to communicate
      complex health information to people with low health literacy. This format can
      even bridge the information processing gap between audiences with low and high
      health literacy as the recall differences between the two groups are eliminated.
      As animations do not negatively influence high health literate audiences, it is
      concluded that information adapted to audiences with low health literacy suits
      people with high health literacy as well.

PMID- 25586712
TI  - Transfer of natalizumab into breast milk in a mother with multiple sclerosis.
AB  - Natalizumab (Tysabri) is a recombinant humanized antibody to alpha4-integrin that
      is approved by the Food and Drug Administration for the treatment of multiple
      sclerosis (MS) and Crohn disease. This is a case report of a 28-year-old woman
      with MS who was taking natalizumab (300 mg intravenously infused over 1 hour
      every 4 weeks) while breastfeeding her 11.5-month-old daughter 3 times a day.
      Breast milk samples were collected over a 50-day period after the patient's first
      drug infusion. The average concentration of natalizumab was 0.93 ug/mL/d, and the
      relative infant dose was 1.74% of the weight-adjusted maternal dose. Transfer of
      natalizumab into human milk increased over time and with subsequent injections,
      with the highest concentration of 2.83 ug/mL at day 50 with a relative infant
      dose of 5.3%. Because these data suggest continued accumulation of natalizumab in
      milk, and because we cannot provide an accurate assessment of levels of this drug
      at 24 weeks (steady state), we are unable to determine safety at this time. 

PMID- 25586714
TI  - Early results of surgical management of conjunctival dermolipoma: partial
      excision and free conjunctival autograft.
AB  - BACKGROUND AND AIMS: There is a paucity of data in the literature on the surgical
      management of conjunctival dermolipoma. In this study, we report outcomes of a
      partial mass excision technique (excision of the portion visible when eyes open)
      and free conjunctival autograft. METHODS: Medical records of 13 patients with
      dermolipoma who had undergone partial mass excision at Seoul National University
      Hospital from January 1999 to May 2014 were retrospectively reviewed. After
      resection of the visible part of tumour, including the overlying thick surface
      conjunctiva, the conjunctival defects were reconstructed with free conjunctival
      autograft harvested from the contralateral superior bulbar area. RESULTS: The
      median postoperative follow-up period was 5 months (range 1-84 months). The
      cosmetic surgical results were satisfactory in all 13 patients. Three patients
      showed thick texture on the grafted surgical area postoperatively, but there was
      no significant scar formation resulting in restrictive symblepharon or eye
      movement limitation. There were no other significant complications, such as
      blepharoptosis, diplopia or keratoconjunctivitissicca during the follow-up
      period. CONCLUSIONS: Partial mass (visible part only) excision, including that of
      the overlying thick conjunctiva, and free conjunctival autograft from the
      opposite eye, is a relatively simple and effective technique for the surgical
      management of conjunctival dermolipoma.

PMID- 25586713
TI  - Extending the diabetic retinopathy screening interval beyond 1 year: systematic
      review.
AB  - To determine whether the recommended screening interval for diabetic retinopathy
      (DR) in the UK can safely be extended beyond 1 year. Systematic review of
      clinical and cost-effectiveness studies. Nine databases were searched with no
      date restrictions. Randomised controlled trials (RCTs), cohort studies,
      prognostic or economic modelling studies which described the incidence and
      progression of DR in populations with type 1 diabetes mellitus or type 2 diabetes
      mellitus of either sex and of any age reporting incidence and progression of DR
      in relation to screening interval (vs annual screening interval) and/or
      prognostic factors were included. Narrative synthesis was undertaken. 14,013
      papers were identified, of which 11 observational studies, 5 risk stratification
      modelling studies and 9 economic studies were included. Data were available for
      262,541 patients of whom at least 228,649 (87%) had type 2 diabetes. There were
      no RCTs. Studies concluded that there is little difference between clinical
      outcomes from screening 1 yearly or 2 yearly in low-risk patients. However there
      was high loss to follow-up (13-31%), heterogeneity in definitions of low risk and
      variation in screening and grading protocols for prior retinopathy results.
      Observational and economic modelling studies in low-risk patients show little
      difference in clinical outcomes between 1-year and 2-year screening intervals.
      The lack of experimental research designs and heterogeneity in definition of low
      risk considerably limits the reliability and validity of this conclusion. Cost
      effectiveness findings were mixed. There is insufficient evidence to recommend a
      move to extend the screening interval beyond 1 year.

PMID- 25586715
TI  - MultiColor imaging in the evaluation of geographic atrophy due to age-related
      macular degeneration.
AB  - PURPOSE: To compare different imaging modalities and to investigate the ability
      of MultiColor to evaluate geographic atrophy (GA) due to age-related macular
      degeneration (AMD). METHODS: Twenty-two consecutive patients with GA underwent
      MultiColor, colour fundus photography, blue fundus autofluorescence (FAF)
      (excitation=488 nm; emission >500 nm), near-infrared FAF (NIR-FAF)
      (excitation=787 nm; emission >800 nm) and spectral-domain optical coherence
      tomography (SD-OCT) (Spectralis HRA+OCT; Heidelberg Engineering) imaging. Two
      readers independently measured the size (area) and the width of GA (on horizontal
      SD-OCT scan cutting the fovea), and evaluated the foveal sparing in each
      examination. RESULTS: A total of 32 eyes (22 patients, mean age 79.2+/-8 years)
      with GA were included. Intragrader and intergrader agreement considering the
      evaluation of the size and width of GA was high for all the examinations.
      MultiColor and FAF showed the greatest intergrader agreement for GA area
      measurement (intraclass correlation (ICC)=0.990, 95% CI 0.980 to 0.995;
      ICC=0.998, 95% CI 0.996 to 0.999, respectively). SD-OCT showed the highest
      intergrader agreement of foveal involvement (k=1), followed by MultiColor and NIR
      FAF (k=0.68). CONCLUSIONS: We demonstrated that several different imaging
      modalities currently available in clinical practice are reliable for evaluating
      GA due to AMD. MultiColor is an excellent tool for the measurement of GA area and
      width, and for the detection of foveal sparing.

PMID- 25586716
TI  - Mercury and other trace elements in Ohio River fish collected near coal-fired
      power plants: Interspecific patterns and consideration of consumption risks.
AB  - Many coal-fired electric generating facilities in the United States are
      discharging higher loads of Hg, Se, and other chemicals to receiving streams due
      to the installation of flue gas desulfurization (FGD) air pollution control
      units. There are regulatory concerns about the potential increased uptake of
      these bioaccumulative trace elements into food webs. We evaluated the
      concentrations of As, total Hg (THg), methylmercury (MeHg), and Se in Ohio River
      fish collected proximal to coal-fired power plants, of which 75% operate FGD
      systems. Fillet samples (n = 50) from 6 fish species representing 3 trophic
      levels were analyzed. Geometric mean fillet concentrations of THg (wet wt), MeHg
      (wet wt), and Se (dry wt) in 3 species were 0.136, 0.1181, and 3.19 mg/kg
      (sauger); 0.123, 0.1013, and 1.56 mg/kg (channel catfish); and 0.127, 0.0914, and
      3.30 mg/kg (hybrid striped bass). For all species analyzed, only 3 fillet samples
      (6% of total) had MeHg concentrations that exceeded the US Environmental
      Protection Agency (USEPA) human health criterion (0.3 mg/kg wet wt); all of these
      were freshwater drum aged >= 19 y. None of the samples analyzed exceeded the
      USEPA proposed muscle and whole body Se thresholds for protection against
      reproductive effects in freshwater fish. All but 8 fillet samples had a total As
      concentration less than 1.0 mg/kg dry wt. Mean Se health benefit values (HBVSe )
      for all species were >= 4, indicating that potential Hg-related health risks
      associated with consumption of Ohio River fish are likely to be offset by
      adequate Se concentrations. Overall, we observed no measurable evidence of
      enhanced trace element bioaccumulation associated with proximity to power plant
      FGD facilities, however, some enhanced bioaccumulation could have occurred in the
      wastewater mixing zones. Furthermore, available evidence indicates that, due to
      hydraulic and physical factors, the main stem Ohio River appears to have low net
      Hg methylation potential.

PMID- 25586718
TI  - A study on the encapsulation of an occludin lipophilic derivative in liposomal
      carriers.
AB  - Many peptides and proteins, although potentially useful for the treatment of
      various diseases, are hindered in their clinical use by poor oral absorption and
      rapid enzymatic degradation. One of the available solutions to these problems is
      to increase the lipophilicity by conjugating the peptides to lipophilic moieties,
      making them more able to cross the biomembranes by passive transport. Occludin is
      a 65-kDa integral plasma-membrane protein located at the tight junctions. This
      protein and the peptide derived from it have potential clinical application for
      drug delivery. Peptide OP90-103 (1) is a fragment of occludin that shows a very
      poor oral bioavailability and is highly susceptible to enzymatic degradation. The
      conjugation of 1 with two lipoamino acid (LAA) moieties has been shown to enhance
      its lipophilicity and bioavailability, as well as its enzymatic stability. The
      purpose of this study was to evaluate the possibility of encapsulating
      fluorescein modified lipidated OP90-103 (2), in unilamellar- (LUV) and
      multilamellar liposomes (MLV), which have a different composition and surface
      charge and are produced by different methods. The cell internalization of the
      carrier systems was evaluated in vitro. 

PMID- 25586719
TI  - Cell Staining by Photo-activated Dye and Its Conjugate with Chitosan.
AB  - Photo-activated or "Caged" rhodamine dyes are the most useful for microscopic
      investigation of biological tissue by various fluorescent techniques. Novel
      precursor of the fluorescent dye (PFD813) has been studied for photosensitive
      staining of numerous animal cells. The functional rhodamine dye (Rho813) with
      intensive fluorescence has been obtained after photoactivation of its precursor
      PFD813 inside cells. The dye Rho813 has been successfully used for the optical
      detection of particular features in biological objects (HaCaT cells, HBL-100,
      MDCK, lymphocytes). Moreover, the chitosan conjugate with PFD molecules
      ("Chitosan-PFD813") has been obtained and studied for the first time. The
      developed procedures and obtained data are important for further applications of
      novel precursors of fluorescent dyes ("caged" dyes) for microscopic probing of
      biological objects. As example, the synthesized "Chitosan-PFD813" has been
      successfully applied in this study for intracellular transport visualization by
      fluorescent microscopy. 

PMID- 25586717
TI  - Cocaine induces nuclear export and degradation of neuronal retinoid X receptor
      gamma via a TNF-alpha/JNK- mediated mechanism.
AB  - Cocaine abuse represents an immense societal health and economic burden for which
      no effective treatment currently exists. Among the numerous intracellular
      signaling cascades impacted by exposure to cocaine, increased and aberrant
      production of pro-inflammatory cytokines in the CNS has been observed.
      Additionally, we have previously reported a decrease in retinoid-X-receptor-gamma
      (RXR-gamma) in brains of mice chronically exposed to cocaine. Through obligate
      heterodimerization with a number of nuclear receptors, RXRs serve as master
      regulatory transcription factors, which can potentiate or suppress expression of
      a wide spectrum of genes. Little is known about the regulation of RXR levels, but
      previous studies indicate cellular stressors such as cytokines negatively
      regulate levels of RXRs in vitro. To evaluate the mechanism underlying the
      cocaine-induced decreases in RXR-gamma levels observed in vivo, we exposed
      neurons to cocaine in vitro and examined pathways which may contribute to
      disruption in RXR signaling, including activation of stress pathways by cytokine
      induction. In these studies, we provide the first evidence that cocaine exposure
      disrupts neuronal RXR-gamma signaling in vitro by promoting its nuclear export
      and degradation. Furthermore, we demonstrate this effect may be mediated, at
      least in part, by cocaine-induced production of TNF-alpha and its downstream
      effector c-Jun-NH-terminal kinase (JNK). Findings from this study are therefore
      applicable to both cocaine abuse and to pathological conditions characterized by
      neuroinflammatory factors, such as neurodegenerative disease. 

PMID- 25586720
TI  - Comparison of Gene Expression Profile Between Tumor Tissue and Adjacent Non-tumor
      Tissue in Patients with Gastric Gastrointestinal Stromal Tumor (GIST).
AB  - Gastrointestinal stromal tumors (GISTs) are defined as spindle cell and/or
      epithelioid tumors originated from interstitial Cajal cells or precursors in the
      digestive tract. This study was conducted to identify genes differing in
      expression between the gastric tumors and the adjacent non-cancerous mucosas in
      patients with primary gastric GIST. The gene expression profile was determined by
      using oligonucleotide-based DNA microarrays and further validated by quantitative
      real-time PCR. The Kyoto encyclopedia of genes and genomes (KEGG) pathway
      analysis was performed to predict signaling pathways involved in gastric GIST.
      Our data showed that the expression levels of 957 genes (RAB39B, member RAS
      oncogene family; VCAN, versican; etc.) were higher and that of 526 genes (CXCL14,
      chemokine C-X-C motif ligand 14; MTUS1, microtubule-associated tumor suppressor
      1; etc.) were lower in the gastric tumor tissues as compared with normal gastric
      tissues. Results from KEGG pathway analysis revealed that the differentially
      expressed genes were enriched into 16 signaling transduction pathways, including
      Hedeghog and Wnt signaling pathways. Our study may provide basis for
      identification of novel biomarkers associated with primary gastric GIST
      pathogenesis and for exploration of underlying mechanisms involved in this
      gastric sarcoma. 

PMID- 25586722
TI  - Gas-separation membranes loaded with porous aromatic frameworks that improve with
      age.
AB  - Porosity loss, also known as physical aging, in glassy polymers hampers their
      long term use in gas separations. Unprecedented interactions of porous aromatic
      frameworks (PAFs) with these polymers offer the potential to control and exploit
      physical aging for drastically enhanced separation efficiency. PAF-1 is used in
      the archetypal polymer of intrinsic microporosity (PIM), PIM-1, to achieve three
      significant outcomes. 1) hydrogen permeability is drastically enhanced by 375% to
      5500 Barrer. 2) Physical aging is controlled causing the selectivity for H2 over
      N2 to increase from 4.5 to 13 over 400 days of aging. 3) The improvement with age
      of the membrane is exploited to recover up to 98% of H2 from gas mixtures with N2
      . This process is critical for the use of ammonia as a H2 storage medium. The
      tethering of polymer side chains within PAF-1 pores is responsible for
      maintaining H2 transport pathways, whilst the larger N2 pathways gradually
      collapse.

PMID- 25586721
TI  - Structural dynamics of native and V260E mutant C-terminal domain of HIV-1
      integrase.
AB  - The C-terminal domain (CTD) of HIV-1 integrase is a five stranded beta-barrel
      resembling an SH3 fold. Mutational studies on isolated CTD and full-length IN
      have reported V260E mutant as either homo-dimerization defective or affecting the
      stability and folding of CTD. In this study, molecular dynamics simulation
      techniques were used to unveil the effect of V260E mutation on isolated CTD
      monomer and dimer. Both monomeric and dimeric forms of wild type and V260E mutant
      are highly stable during the simulated period. However, the stabilizing pi
      stacking interaction between Trp243 and Trp243' at the dimer interface is highly
      disturbed in CTD-V260E (>6 A apart). The loss in entropy for dimerization is -30
      and -25 kcal/mol for CTD-wt and CTD-V260E respectively signifying a weak
      hydrophobic interaction and its perturbation in CTD-V260E. The mutant Glu260
      exhibits strong attraction/repulsion with all the basic/acidic residues of CTD.
      In addition to this, the dynamics of CTD-wild type and V260E monomers at 498 K
      was analyzed to elucidate the effect of V260E mutation on CTD folding. Increase
      in SASA and reduction in the number of contacts in CTD-V260E during simulation
      highlights the instability caused by the mutation. In general, V260E mutation
      affects both multimerization and protein folding with a pronounced effect on
      protein folding rather than multimerization. This study emphasizes the importance
      of the hydrophobic nature and SH3 fold of CTD in proper functioning of HIV
      integrase and perturbing this nature would be a rational approach toward
      designing more selective and potent allosteric anti-HIV inhibitors. 

PMID- 25586723
TI  - Cross-resistance and interactions between Bt toxins Cry1Ac and Cry2Ab against the
      cotton bollworm.
AB  - To delay evolution of pest resistance to transgenic crops producing insecticidal
      proteins from Bacillus thuringiensis (Bt), the "pyramid" strategy uses plants
      that produce two or more toxins that kill the same pest. We conducted laboratory
      diet experiments with the cotton bollworm, Helicoverpa armigera, to evaluate
      cross-resistance and interactions between two toxins in pyramided Bt cotton
      (Cry1Ac and Cry2Ab). Selection with Cry1Ac for 125 generations produced 1000-fold
      resistance to Cry1Ac and 6.8-fold cross-resistance to Cry2Ab. Selection with
      Cry2Ab for 29 generations caused 5.6-fold resistance to Cry2Ab and 61-fold cross
      resistance to Cry1Ac. Without exposure to Bt toxins, resistance to both toxins
      decreased. For each of the four resistant strains examined, 67 to 100% of the
      combinations of Cry1Ac and Cry2Ab tested yielded higher than expected mortality,
      reflecting synergism between these two toxins. Results showing minor cross
      resistance to Cry2Ab caused by selection with Cry1Ac and synergism between these
      two toxins against resistant insects suggest that plants producing both toxins
      could prolong the efficacy of Bt cotton against this pest in China. Including
      toxins against which no cross-resistance occurs and integrating Bt cotton with
      other control tactics could also increase the sustainability of management
      strategies. 

PMID- 25586724
TI  - Postoperative impairment of motor function at train-of-four ratio >=0.9 cannot be
      improved by sugammadex (1 mg kg-1).
AB  - BACKGROUND: A train-of-four ratio (TOFR) >=0.9 measured by quantitative
      neuromuscular monitoring is accepted as an indication of sufficient neuromuscular
      recovery for extubation, even though many postsynaptic acetylcholine receptors
      may still be inhibited. We investigated whether antagonism with sugammadex after
      spontaneous recovery to TOFR>=0.9 further improves muscle function or subjective
      well-being. METHODS: Following recovery to TOFR>=0.9 and emergence from
      anaesthesia, 300 patients randomly received either sugammadex 1.0 mg kg(-1) or
      placebo. Fine motor function (Purdue Pegboard Test) and maximal voluntary grip
      strength were measured before and after surgery (before and after test drug
      administration). At discharge from the postanaesthesia care unit, well-being was
      assessed with numerical analogue scales and the Quality-of-Recovery Score 40 (QoR
      40). RESULTS: Patients' fine motor function [6 (sd 4) vs 15 (3) pegs (30 s)(-1),
      P<0.05] and maximal voluntary grip strength (284 (126) vs 386 (125) N, P<0.05)
      were significantly lower after anaesthesia compared with the pre-anaesthesia
      baseline. After sugammadex or placebo, motor function was significantly improved
      in both groups but did not reach the preoperative level. There was no difference
      between groups at any time. Global well-being was unaffected (QoR-40: placebo,
      174 vs 185; sugammadex, 175 vs 186, P>0.05). CONCLUSIONS: Antagonizing rocuronium
      at TOF>=0.9 with sugammadex 1.0 mg kg(-) (1) did not improve patients' motor
      function or well-being when compared with placebo. Our data support the view that
      TOFR>=0.9 measured by electromyography signifies sufficient recovery of
      neuromuscular function. CLINICAL TRIAL REGISTRATION: The trial is registered at
      ClinicalTrials.gov (NCT01101139).

PMID- 25586725
TI  - Variability in practice and factors predictive of total crystalloid
      administration during abdominal surgery: retrospective two-centre analysis.
AB  - BACKGROUND: Variation in clinical practice in the perioperative environment and
      intensive care unit is a major challenge facing modern medicine. The objective of
      the present study was to analyse intraoperative crystalloid administration
      practices at two academic medical centres in the USA. METHODS: We extracted
      clinical data from patients undergoing intra-abdominal procedures performed at UC
      Irvine (UCI) and Vanderbilt University (VU) Medical Centres. Limiting data to
      uncomplicated elective surgery with minimal blood loss, we quantified variability
      in fluid administration within individual providers, between providers, and
      between types of procedures using a corrected coefficient of variation (cCOV).
      Regression was performed using a general linear model to determine factors most
      predictive of fluid administration. RESULTS: For provider analysis and model
      building, 1327 UCI and 4585 VU patients were used. The average corrected
      crystalloid infusion rate across all providers at both institutions was 7.1 (sd
      4.9) ml kg(-1) h(-1), an overall cCOV of 70%. Individual providers ranged from
      2.3 (sd 3.7) to 14 (sd 10) ml kg(-1) h(-1). The final regression model strongly
      favoured personnel as predictors over other patient predictors. CONCLUSIONS: Wide
      variability in crystalloid administration was observed both within and between
      individual anaesthesia providers, which might contribute to variability in
      surgical outcomes.

PMID- 25586726
TI  - Population pharmacokinetics of epsilon-aminocaproic acid in adolescents
      undergoing posterior spinal fusion surgery.
AB  - BACKGROUND: Despite demonstrated efficacy of epsilon-aminocaproic acid (EACA) in
      reducing blood loss in adolescents undergoing spinal fusion, there are no
      population-specific pharmacokinetic data to guide dosing. The aim of this study
      was to determine the pharmacokinetics of EACA in adolescents undergoing spinal
      fusion surgery and make dosing recommendations. METHODS: Twenty children ages 12
      17 years were enrolled, with 10 children in each of two groups based on diagnosis
      (idiopathic scoliosis or non-idiopathic scoliosis). Previously reported data from
      infants undergoing craniofacial surgery were included in the model to enable
      dosing recommendations over a wide range of weights, ages, and diagnoses. A
      population non-linear mixed effects modelling approach was used to characterize
      EACA pharmacokinetics. RESULTS: Population pharmacokinetic parameters were
      estimated using a two-compartment disposition model with allometrically scaled
      weight and an age effect on clearance. Pharmacokinetic parameters for the typical
      patient were a plasma clearance of 153 ml min(-1) 70 kg(-1) (6.32 ml min(-1) kg(
      0.75)), intercompartmental clearance of 200 ml min(-1) 70 kg(-1) (8.26 ml min(-1)
      kg(-0.75)), central volume of distribution of 8.78 litre 70 kg(-1) (0.13 litre
      kg(-1)), and peripheral volume of distribution of 15.8 litre 70 kg(-1) (0.23
      litre kg(-1)). Scoliosis aetiology did not have a clinically significant effect
      on drug pharmacokinetics. CONCLUSIONS: The following dosing schemes are
      recommended according to patient weight: weight <25 kg, 100 mg kg(-1) loading
      dose and 40 mg kg(-1) h(-1) infusion; weight <=25 kg-<50 kg, 100 mg kg(-1)
      loading dose and 35 mg kg(-1) h(-1) infusion; and weight >=50 kg, 100 mg kg(-1)
      loading dose and 30 mg kg(-1) h(-1) infusion. An efficacy trial employing this
      dosing strategy is warranted. CLINICAL TRIAL REGISTRATION: NCT01408823.

PMID- 25586728
TI  - Point prevalence of surgical checklist use in Europe: relationship with hospital
      mortality.
AB  - BACKGROUND: The prevalence of use of the World Health Organization surgical
      checklist is unknown. The clinical effectiveness of this intervention in
      improving postoperative outcomes is debated. METHODS: We undertook a
      retrospective analysis of data describing surgical checklist use from a 7 day
      cohort study of surgical outcomes in 28 European nations (European Surgical
      Outcomes Study, EuSOS). The analysis included hospitals recruiting >10 patients
      and excluding outlier hospitals above the 95th centile for mortality.
      Multivariate logistic regression and three-level hierarchical generalized mixed
      models were constructed to explore the relationship between surgical checklist
      use and hospital mortality. Findings are presented as crude and adjusted odds
      ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 45 591
      patients from 426 hospitals were included in the analysis. A surgical checklist
      was used in 67.5% patients, with marked variation across countries (0-99.6% of
      patients). Surgical checklist exposure was associated with lower crude hospital
      mortality (OR 0.84, CI 0.75-0.94; P=0.002). This effect remained after adjustment
      for baseline risk factors in a multivariate model (adjusted OR 0.81, CI 0.70
      0.94; P<0.005) and strengthened after adjusting for variations within countries
      and hospitals in a three-level generalized mixed model (adjusted OR 0.71, CI 0.58
      0.85; P<0.001). CONCLUSIONS: The use of surgical checklists varies across
      European nations. Reported use of a checklist was associated with lower
      mortality. This observation may represent a protective effect of the surgical
      checklist itself, or alternatively, may be an indirect indicator of the quality
      of perioperative care. CLINICAL TRIAL REGISTRATION: The European Surgical
      Outcomes Study is registered with ClinicalTrials.gov, number NCT01203605.

PMID- 25586727
TI  - Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage:
      randomized controlled trial.
AB  - BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of
      fibrinogen is associated with excessive subsequent bleeding and blood
      transfusion. We hypothesized that pre-emptive treatment with fibrinogen
      concentrate reduces the need for red blood cell (RBC) transfusion in patients
      with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded,
      parallel randomized controlled trial, we assigned subjects with severe PPH to a
      single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or
      equivalent was given to all subjects independent of body weight and the
      fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up
      to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of
      blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC
      transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe
      PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at
      least 4 units of RBCs, haemostatic intervention (angiographic embolization,
      surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the
      249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the
      placebo group were included in the intention-to-treat analysis. At inclusion the
      subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean
      fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group
      received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby
      significantly increasing fibrinogen concentration compared with placebo by 0.40 g
      litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood
      transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the
      placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88).
      We found no difference in any predefined secondary outcomes, per-protocol
      analyses, or adjusted analyses. No thromboembolic events were detected.
      CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as
      pre-emptive treatment for severe PPH in patients with normofibrinogenaemia.
      CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov:
      http://clinicaltrials.gov/show/NCT01359878. Published protocol:
      http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

PMID- 25586729
TI  - Aberrant right subclavian artery in fetuses with Down syndrome: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: The primary objective was to estimate the prevalence of aberrant
      right subclavian artery (ARSA) in fetuses with Down syndrome. Secondary
      objectives were to assess the prevalence of ARSA in euploid fetuses, the
      feasibility of ultrasound evaluation of the right subclavian artery (RSA) in the
      first and second trimesters of pregnancy, the performance of ARSA in screening
      for trisomy 21 and its association with other abnormalities. METHODS: Web-based
      databases (PubMed, EMBASE and MEDLINE) were searched up to July 2014. The STROBE,
      PRISMA and QUIPS instruments were used to assess all included studies and for
      reporting of methodology, results and conclusions. Original studies that reported
      prenatal ultrasound evaluation of ARSA, assessment of its prevalence in Down
      syndrome and euploid fetuses, feasibility of ultrasound evaluation of the RSA in
      the first and second trimesters of pregnancy and correlation of ARSA with other
      abnormalities were included, excluding duplications and case reports. Collected
      data were summarized to estimate prevalence and feasibility. A meta-analysis was
      performed pooling the study-specific positive and negative likelihood ratios (LR+
      and LR-), detection rates and false-positive rates for trisomy 21. RESULTS:
      Prevalence of ARSA in Down-syndrome fetuses was 23.6% (95% CI, 19.4-27.9%),
      whereas in euploid fetuses it was 1.02% (95% CI, 0.86-1.10%). Ultrasound
      evaluation of the RSA course and origin in the first and second trimesters of
      pregnancy was feasible in 85% and 98% of cases (first and second trimester,
      respectively) and it was directly related to sonographic experience and fetal
      crown-rump length and inversely related to maternal body mass index. In more than
      20% of fetuses with ARSA there was an association with other abnormalities but
      ARSA seemed to be an independent marker of trisomy 21. The meta-analysis showed
      that ARSA is a significant risk factor for Down syndrome (pooled LR+ = 26.93, 95%
      CI, 19.36-37.47, P for effect < 0.001, P for Q = 0.3, I(2) = 17.3%), whereas
      normal RSA is a significant protective marker (pooled LR- = 0.71, 95% CI, 0.51
      0.99, P for effect = 0.043, P for Q = 0.9, I(2) = 0%). CONCLUSIONS: ARSA appears
      to be a clinically useful prenatal ultrasound marker of Down syndrome. Additional
      testing when ARSA is diagnosed should involve evaluation of all risk factors by
      applying a mathematical model. There is insufficient evidence to recommend fetal
      karyotyping in cases with isolated ARSA. If the background risk is higher or
      additional markers are present, full fetal karyotyping is advisable, including
      analysis for 22q11 microdeletion.

PMID- 25586731
TI  - Feasibility and safety of left ventricular endomyocardial biopsy via transradial
      access: Technique and initial experience.
AB  - BACKGROUND: Endomyocardial biopsy constitutes an essential part of the diagnostic
      algorithm in patients with heart failure of unknown origin, but usually requires
      transfemoral access. METHODS AND RESULTS: Here, we describe a novel method that
      allows interventional cardiologists to obtain left ventricular biopsies via
      transradial access with a 7.5F sheathless multipurpose (MP1.0) guiding catheter.
      This approach was successfully conducted in 37 consecutive patients at our
      institution with only one intraprocedural minor complication (ventricular
      fibrillation during insertion of the guiding catheter). CONCLUSIONS: Transradial
      access to obtain left ventricular endomyocardial biopsies is a feasible and safe
      option for experienced radial operators.

PMID- 25586732
TI  - The imperative to prevent and treat childhood obesity: why the world cannot
      afford to wait.
AB  - In the past 20 years, the prevalence of obesity in the United States increased
      almost 50% among adults and by 300% in children. Today, 9.7% of all U.S. infants
      up to 2 years old have abnormally high weight-for-recumbent length; 25% of
      children under age 5 are either overweight or obese; and 17% of adolescents are
      obese. Ethnic disparities in the rates of obesity are also large and apparent in
      childhood. Further, 44% of obese adolescents have metabolic syndrome. Obese
      children tend to become obese adults; thus, in a decade, young adults will likely
      have much higher risks of chronic disease, which has tremendous implications for
      the healthcare system. However, early childhood may be the best time to prevent
      obesity. Teachers' healthy eating choices are positively associated with changes
      in body mass index percentiles for children, for example. In addition, 8 million
      children attend afterschool programs, which can successfully promote health and
      wellness and successfully treat obesity. This childhood epidemic of obesity and
      its health-related consequences in adolescents should be a clinical and public
      health priority. However, this major public health problem cannot be managed
      solely in clinical settings. Rather, public health strategies must be integrated
      into home and family, school and community-based settings. 

PMID- 25586730
TI  - Virulence and the presence of aminoglycoside resistance genes of Staphylococcus
      haemolyticus strains isolated from clinical specimens.
AB  - We examined thirty methicillin-resistant Staphylococcus haemolyticus isolates
      cultured from clinical specimens for antibiotic resistance, various important
      interactions of the bacteria with epithelial cells and putative virulence
      determinants. All strains were resistant to oxacillin and carried the mecA gene.
      Aminocyclitol-3'-phosphotransferase (aph(3')-IIIa) gene encoding
      nucleotidyltransferases was detected in 43 %, aminocyclitol-6'-acetyltransferase
      aminocyclitol-2"-phosphotransferase (aac(6')/aph(2")) gene encoding bifunctional
      acetyltransferases/phosphotransferases in 33 %, aminocyclitol-4'
      adenylyltransferase (ant(4')-Ia) gene encoding phosphotransferases in 20 %. The
      coexistence of resistance to methicillin and aminoglycosides was investigated in
      multi-resistant strains. Coexisting (aac(6')/aph(2")) and (aph(3')-IIIa) genes
      were detected in 33 % of isolates, whereas 63 % of isolates had at least one of
      these genes. All strains revealed adherence ability and most of them (63 %) were
      invasive to epithelial cells. Electron microscopy revealed that the bacteria were
      found in vacuoles inside the cells. We observed that the contact of the bacteria
      with host epithelial cells is a prerequisite to their cytotoxicity at 5 h
      incubation. Culture supernatant of the strains induced a low effect of
      cytotoxicity at the same time of incubation. Cell-free supernatant of all
      isolates expressed cytotoxic activity which caused destruction of HEp-2 cells at
      24 h. None of the strains was cytotonic towards CHO cells. Among thirty strains,
      27 % revealed lipolytic activity, 43 % produced lecithinase and 20 % were
      positive for proteinase activity. Analyses of cellular morphology and DNA
      fragmentation exhibited typical characteristic features of those undergoing
      apoptosis. The Pearson linear test revealed positive correlations between the
      apoptotic index at 24 h and percentage of cytotoxicity. Our results provided new
      insights into the mechanisms contributing to the development of S. haemolyticus
      associated infections. The bacteria adhered and invaded to non-professional
      phagocytes. The invasion of epithelial cells by S. haemolyticus could be similar
      to phagocytosis that requires polymerization of the actin cytoskeleton. The
      process is inhibited by cytochalasin D. Moreover, they survived within the cells
      by residing in membrane bound compartments and induced apoptotic cell death. 

PMID- 25586734
TI  - The relationship of distance from the surgical centre on attendance and weight
      loss after laparoscopic gastric bypass surgery in the United Kingdom.
AB  - Obesity remains a significant worldwide health problem and is currently
      increasing. Surgery remains the only proven long-term intervention and has been
      shown to be cost-effective. Evidence suggests that regular follow-up following
      laparoscopic adjustable gastric banding is related to improved outcome, such
      evidence is lacking for laparoscopic gastric bypass surgery (laparoscopic Roux-en
      Y gastric bypass [LRYGB]). This study examines the effect of distance on
      attendance at post-operative clinics and subsequent weight loss following
      surgery. A prospectively maintained database was interrogated to analyze patients
      undergoing LRYGB before August 2010. Patient demographics, percentage excess
      weight loss (%EWL), compliance with out-patient clinic attendances and the
      distance the patients lived from the hospital were examined. Perfect clinic
      attendees were compared with non-attendees and the distances patients lived from
      the hospital evaluated. There was a significantly greater %EWL at 1 year post-op
      observed in the perfect attendees group (65.5 vs. 59.5, P = 0.01). Increased %EWL
      was also evident at 2 years post-op but did not reach statistical significance
      (66.9 vs. 59.5, P = 0.06). There was a negative correlation observed between post
      operative weight loss and distance from the bariatric centre (R = -0.21, P =
      0.04). Close follow-up following LRYGB is essential to optimize outcomes.
      Increased frequency of out-patient clinic visits was associated with improved
      post-operative weight loss. Increasing distance between the patient's home and
      the bariatric centre was associated with worse post-operative weight loss. 

PMID- 25586733
TI  - An intragastric balloon produces large weight losses in the absence of a change
      in ghrelin or peptide YY.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?: The development of obesity is a multi
      factorial process that results in an alteration in the neuroendocrine hormones
      that help regulate appetite and body weight. Weight loss has been shown to alter
      this neuroendocrine balance so as to promote weight regain. An intragastric
      balloon is an effective method to achieve significant weight loss in obese
      patients and is well suited for those patients who are looking for an alternative
      to lifestyle modification alone, and those who are not ready or suitable for
      surgical intervention. Limited research has shown that the weight loss achieved
      with an intragastric balloon is mediated by altered secretion of the hormones
      that regulate appetite and weight. WHAT DOES THIS STUDY ADD?: There are currently
      limited data on the effects of intragastric balloons on appetite and weight
      related hormones. In the current study, we have investigated a broad range of gut
      hormones and adipokines and their response to weight loss induced by differing
      methods, and the subsequent effect this may have on weight regain. This is an
      important research area as novel therapies and long-term strategies are needed to
      counteract the unfavourable changes to the neuroendocrine control of appetite and
      satiety associated with diet-induced weight loss. This study aims to determine
      the effect of weight loss achieved with different methods on fasting levels of
      appetite hormones. Sixty-six obese adults with metabolic syndrome were randomized
      to intragastric balloon (IGB) for 6 months, with a 12-month behavioural
      modification programme (IGB group, 'IGBG') or a 12-month behavioural modification
      programme alone (control group, 'CG'). Anthropometric assessments and blood
      samples were taken every 3 months and total ghrelin, peptide YY (PYY),
      adiponectin and leptin were measured. Significant weight-loss differences
      favouring the IGBG were evident between groups at all time points. Ghrelin
      increased when the IGB was in situ (+39.3 pmol L(-1) vs. baseline) and returned
      to baseline after its removal (-34.7 pmol L(-1) ). Adiponectin and PYY levels
      remained stable in the IGBG, with transient increases noted in the CG. There were
      no significant between-group differences for ghrelin, PYY or adiponectin. In the
      IGBG, despite a decrease in leptin at 6 months (-11.7 ng mL(-1) ), levels
      increased to baseline after IGB removal (-3.7 ng mL(-1) ). In summary, weight
      loss associated with the IGB did not alter fasting levels of PYY or adiponectin.
      There was a return of ghrelin and leptin levels to baseline values after IGB
      removal. No compensatory rise in ghrelin was evident in either group 12 months
      after initial weight reduction, suggesting that such treatment strategies may
      lead to better long-term sustainable weight loss. 

PMID- 25586735
TI  - Patients' experiences after bariatric surgery: a qualitative study at 12-month
      follow-up.
AB  - This study used a qualitative approach to understand patients' experiences in
      post-surgery adaptation related to bariatric surgery, 12 months after this
      procedure. The study population included 30 obese adults, with a mean age of
      40.17 years, who were interviewed 12 months after bariatric surgery. Individual
      interviews, using open-ended questions, were audiotaped, transcribed and coded
      according to the grounded theory methodology. The data showed that the subjects
      described themselves as belonging to one of two opposite and separate groups:
      success or failure. In both groups, two core categories emerged from the data:
      outcomes and treatment. Previous expectations were reached by the patients who
      described themselves as successful, with some remaining concerns related to
      future weight maintenance and aesthetics issues. The failure group emphasized
      their unmet expectations and the expectancy that surgery would change their lives
      remained. Treatment in the successful cases integrated lifestyle changes and
      bariatric surgery, highlighting the personal commitment required to achieve the
      objectives. The failure group emphasized bariatric surgery without personal
      commitment, and healthy eating behaviour was understood as a sacrifice. The post
      surgical adaptation experiences were diverse: the cases that were described as a
      success highlighted lifestyle changes, personal efforts and commitment with the
      global treatment process. External understanding and the desire for a miracle
      surgery characterized the cases described as a failure. According to these
      results, it is necessary to promote adequate information about the whole process
      and skills required to ensure commitment in all treatment dimensions. 

PMID- 25586736
TI  - Emergence of New Onset substance use disorders among post-weight loss surgery
      patients.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Elevated rates of substance use
      disorders (SUDs), particularly (but not only) alcohol use, are observed among
      post-weight loss surgery (WLS) patients. The development of SUDs among post-WLS
      patients typically occurs 1-2 years post-surgery. Post-WLS patients are
      developing SUD at a much later time of life than is typical of SUDs in the
      general population, suggesting they constitute a distinct SUD phenotype that is
      directly related to having undergone WLS. WHAT THIS STUDY ADDS: Overall, findings
      suggest that post-WLS patients are overrepresented in substance abuse treatment
      programmes, and the majority of them report no history of SUD before WLS.
      Relative to non-WLS patients in SUD treatment, post-WLS patients in substance
      abuse treatment are disproportionally diagnosed with alcohol dependence,
      including alcohol withdrawal. Post-WLS patients may be at elevated risk for
      development of New Onset SUD in the absence of a prior SUD history; this group is
      phenotypically different from those with a history of substance abuse prior to
      surgery, and such patients may have unique treatment needs. A comprehensive
      substance abuse treatment facility began observing increased admissions who
      reported histories of weight loss surgery (WLS). Emerging evidence suggests that
      roughly half of post-WLS patients in substance abuse treatment developed their
      substance use disorder (SUD) after surgery. The present study examined
      differences between SUD patients who developed New Onset SUD after surgery and
      those with a reported SUD onset before WLS (SUD Hx+ group). Participants
      completed a questionnaire and participated in a semi-structured interview. Data
      were also obtained from participants' electronic medical records. Of the total
      treatment sample (n = 4658), 2.8% reported a history of WLS. Post-WLS patients
      were significantly more likely to be diagnosed with alcohol use disorders (AUDs).
      Among post-WLS patients who were interviewed (n = 56), 60% were classified as New
      Onset SUD, while only 40% were SUD Hx+. SUD Hx+ cases reported using
      significantly more types of substances than New Onset cases and were more likely
      to report pre-surgical binge eating disorder (BED). Post-WLS patients are
      overrepresented in substance abuse treatment and are disproportionally diagnosed
      AUDs. Post-WLS patients may be at elevated risk for development of New Onset SUD
      at a time in life (middle age) when SUD onset is relatively uncommon.

PMID- 25586737
TI  - Impact of physical activity and diet on lipoprotein particle concentrations in
      severely obese women participating in a 1-year lifestyle intervention.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Physical activity and high aerobic
      fitness protects against cardiovascular disease and early death, besides having a
      very modest impact on lipoprotein-cholesterol in obese subjects. Physical
      activity has been shown to favourably alter lipoprotein particle concentrations
      and apolipoprotein B with minimal weight loss in overweight to moderately obese
      subjects. WHAT THIS STUDY ADDS: We studied the impact of physical activity on
      lipoprotein subclass particle concentrations in women with severe obesity.
      Increased physical activity duration was associated with favourable changes,
      whereas increased PA intensity was associated with adverse changes in some
      lipoprotein particle subclasses in severely obese women. Severely obese women
      that manage to increase their physical activity level can improve their
      lipoprotein profile, whether or not they lose fat mass Physical activity (PA) and
      high aerobic fitness protects against cardiovascular disease and early death
      possibly among others because of an anti-atherogenic impact on lipoprotein
      particle concentrations. The objective of this study was to determine the impact
      of PA and diet on lipoprotein particle concentrations. Thirty-one severely obese
      women (age 43.6 +/- 10.2 years; body mass index 43.0 +/- 6.3 kg m(-2) )
      participated in a 1-year lifestyle intervention with repeated measurements of
      lipoprotein particle subclass concentrations and size of very low density
      lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein
      (HDL), as well as fat mass, PA and diet. Multiple regression was used to
      determine associations with change (Delta) in two principal components (PCs)
      describing lipoprotein distributions: DeltaPC 1 LIPO (dominated by VLDL and LDL)
      and DeltaPC 2 LIPO (dominated by large HDL and mean HDL particle size). DeltaPA
      duration was the only variable that was significantly related to DeltaPC 1 LIPO
      (partial r = -0.40, P = 0.008), while DeltaPA intensity was the only variable
      that was significantly related to DeltaPC 2 LIPO (partial r = -0.43, P = 0.003)
      in adjusted models. Increased PA duration was associated with favourable changes,
      whereas increased PA intensity was associated with adverse changes in some
      lipoprotein particle subclasses in severely obese women.

PMID- 25586738
TI  - Toward a culturally sensitive conceptualization of resilience: Participatory
      research with war-affected communities in northern Uganda.
AB  - Resilience research with war-affected populations has long conceptualized
      resilience as the absence of psychopathology and operationalized it by use of
      standardized measures. However, literature on resilience increasingly highlights
      the importance of also including indicators of positively valued functioning as
      well as contextually sensitive indicators of resilience. This study used a
      participatory approach to examine the contextual conceptualization of youth
      resilience in the aftermath of war in northern Uganda, as defined by groups of
      stakeholders (youths, parents, elders, leaders, teachers) in four communities.
      The results identify 40 indicators covering a multiplicity of domains of
      functioning. The rationales behind these indicators were clustered into the broad
      themes: progress, self-reliance, social connectedness, morality, health, and
      comfort. The findings suggest that positively and negatively valued aspects of
      functioning are both key to conceptualizing resilience, and indicate the
      importance of including contextually distinguished indicators. The findings
      further point to the role of individual and collective processes in the
      construction of resilience, and to the need to take into account the contexts
      wherein resilience is conceptualized and observed. This study generated
      contextually sensitive indicators of young people's resilience, which can be
      used, complementary to existing measures of functioning, to provide a more
      comprehensive and culturally sensitive view of youths' resilience in the wake of
      war adversity. 

PMID- 25586739
TI  - Training international medical graduates in psychiatry: a cultural adventure.

PMID- 25586740
TI  - MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human
      lung cancer cell line via the transforming growth factor-beta/Smad2/STAT3/STAT5
      pathway.
AB  - Lung cancer is one of the primary causes of mortality worldwide and drug
      resistance is the key contributing factor which results in the failure of lung
      cancer chemotherapy. Previous studies have shown that microRNA (miR)-10a was
      involved in the reversal of cisplatin (DDP) resistance in numerous types of
      tumors; however, the underlying mechanism of action of this remains to be fully
      elucidated. In the present study, miR-10a silencing in human DDP-resistant lung
      cancer A549/DDP cells was demonstrated to improve DDP sensitivity, apoptosis,
      intracellular rhodamine-123 content as well as the expression and activity of
      caspase-3/8. In addition, miR-10a suppressed the cellular expression of P
      glycoprotein, multi-drug resistance protein (MDR) 1, MDR-associated protein 1,
      RhoE, B cell lymphoma-2 and survivin in A549/DDP cells. Furthermore, miR-10a
      silencing inhibited the secretion of transforming growth factor (TGF)-beta,
      phosphorylation of Sma- and Mad-related protein (Smad)2, signal transducer and
      activator of transcription (STAT)3 and STAT5, the transcriptional activity of
      hypoxia-inducible factor and eukaryotic translation initiation factor 4E in human
      lung cancer A549/DDP cell line. These results therefore indicated that miR-10a
      may be a potential target for improving the effectiveness of lung cancer
      chemotherapy via regulation of the TGF-beta/Smad2/STAT3/STAT5 pathway.

PMID- 25586741
TI  - Nitroprusside single-dose prevents the psychosis-like behavior induced by
      ketamine in rats for up to one week.
AB  - Recently, we found a rapid and long-lasting improvement of symptoms in
      schizophrenic patients on antipsychotics after a single four-hour infusion of
      sodium nitroprusside (SNP), a nitric oxide (NO) donor with a short half-life.
      This improvement persisted for up to 4weeks. Because these patients remained on
      antipsychotics after infusion of SNP was finished, the question arises about
      whether this improvement was due to SNP itself. We have now investigated whether
      SNP, alone, can produce preventive antipsychotic effects in rats treated with
      ketamine (KET). 56 adult rats divided into 7 groups were infused with SNP 4mg/kg,
      KET 25mg/kg, or saline as follows: group1 - saline, group2 - SNP, group3 - KET,
      group4 - KET 12h after SNP, group5 - KET 1day after SNP, group6 - KET 2days after
      SNP, and group7 - KET 1week after SNP. The animals were filmed in an open field
      arena for 30min and the videos were later analyzed by ANY-Maze software to
      measure activity and stereotypy. SNP significantly prevented the emergence of
      hyperactivity induced by KET when it was administered for up to 1week before KET,
      and prevented the emergence of stereotypies when it was administered for up to
      1day before KET. These findings in rats, which have an even faster metabolic rate
      than humans, suggest that the long-lasting effects observed in our clinical trial
      with SNP in humans could have been due to SNP itself, and indicate for the first
      time that SNP may present preventive antipsychotic effects. 

PMID- 25586742
TI  - The defect of both angiogenesis and lymphangiogenesis is involved in
      preeclampsia.
AB  - INTRODUCTION: Pre-eclampsia (PE) is characterized by failed remodeling of
      maternal vessels perfusing the placenta. Blood vessels and lymphatic system are
      involved in vessel remodeling and flow homeostasis in the uterus during
      pregnancy. This study aims to investigate the involvement of angiogenesis and
      lymphangiogenesis in PE. METHODS: Placental and decidual tissues were obtained
      from pregnancies with PE (n = 90), including PE cases with decidual vasculopathy
      (DV) (n = 52) and without DV (n = 38), and healthy pregnancies (control, n = 20).
      The clinical characteristics of these groups were analyzed. The expression levels
      of VEGF1, CD34, PROX-1, VEGFR3, and CD31 in the placenta and decidua were
      detected through immunohistochemistry, reverse-transcription polymerase chain
      reaction, and Western blot. RESULTS: The lymphangiogenic markers PROX-1 and
      VEGFR3 were negatively expressed in the placenta but positively expressed in the
      decidua. The expression levels of the angiogenic markers VEGF1 and CD34 and the
      panendothelial marker CD31 were significantly lower in the placenta and decidua
      of the PE group than in those of the control group. The expression levels of
      VEGF1, CD34, and CD31 were significantly lower in the placenta and decidua with
      DV than in those without DV. Furthermore, the expression trends of PROX-1 and
      VEGFR3 was similar to those of VEGF1, CD34, and CD31 among the groups.
      CONCLUSIONS: Lymphangiogenesis occurred in the decidua but not in the placenta.
      Impaired angiogenesis and lymphangiogenesis were associated with PE, particularly
      in the presence of DV.

PMID- 25586743
TI  - Chitosan-based scaffold modified with D-(+) raffinose for cartilage repair: an in
      vivo study.
AB  - BACKGROUND: Osteochondral defects significantly affect patients' quality of life
      and represent challenging tissue lesions, because of the poor regenerative
      capacity of cartilage. Tissue engineering has long sought to promote cartilage
      repair, by employing artificial scaffolds to enhance cell capacity to deposit new
      cartilage. An ideal biomaterial should closely mimic the natural environment of
      the tissue, to promote scaffold colonization, cell differentiation and the
      maintenance of a differentiated cellular phenotype. The present study evaluated
      chitosan scaffolds enriched with D-(+) raffinose in osteochondral defects in
      rabbits. Cartilage defects were created in distal femurs, both on the condyle and
      on the trochlea, and were left untreated or received a chitosan scaffold. The
      animals were sacrificed after 2 or 4 weeks, and samples were analysed
      microscopically. RESULTS: The retrieved implants were surrounded by a fibrous
      capsule and contained a noticeable inflammatory infiltrate. No hyaline cartilage
      was formed in the defects. Although defect closure reached approximately 100% in
      the control group after 4 weeks, defects did not completely heal when filled with
      chitosan. In these samples, the lesion contained granulation tissue at 2 weeks,
      which was then replaced by fibrous connective tissue by week 4. Noteworthy,
      chitosan never appeared to be integrated in the surrounding cartilage.
      CONCLUSIONS: In conclusion, the present study highlights the limits of D-(+)
      raffinose-enriched chitosan for cartilage regeneration and offers useful
      information for further development of this material for tissue repair.

PMID- 25586745
TI  - Debunking myths and enhancing medical student learning within the emergency
      department.

PMID- 25586744
TI  - A BTP1 prophage gene present in invasive non-typhoidal Salmonella determines
      composition and length of the O-antigen of the lipopolysaccharide.
AB  - Salmonella Typhimurium isolate D23580 represents a recently identified ST313
      lineage of invasive non-typhoidal Salmonellae (iNTS). One of the differences
      between this lineage and other non-iNTS S. Typhimurium isolates is the presence
      of prophage BTP1. This prophage encodes a gtrC gene, implicated in O-antigen
      modification. GtrC(BTP) (1) is essential for maintaining O-antigen length in
      isolate D23580, since a gtr(BTP) (1) mutant yields a short O-antigen. This
      phenotype can be complemented by gtrC(BTP) (1) or very closely related gtrC
      genes. The short O-antigen of the gtr(BTP) (1) mutant was also compensated by
      deletion of the BTP1 phage tailspike gene in the D23580 chromosome. This
      tailspike protein has a putative endorhamnosidase domain and thus may mediate O
      antigen cleavage. Expression of the gtrC(BTP) (1) gene is, in contrast to
      expression of many other gtr operons, not subject to phase variation and
      transcriptional analysis suggests that gtrC is produced under a variety of
      conditions. Additionally, GtrC(BTP) (1) expression is necessary and sufficient to
      provide protection against BTP1 phage infection of an otherwise susceptible
      strain. These data are consistent with a model in which GtrC(BTP) (1) mediates
      modification of the BTP1 phage O-antigen receptor in lysogenic D23580, and
      thereby prevents superinfection by itself and other phage that uses the same O
      antigen co-receptor. 

PMID- 25586746
TI  - Mental health facility design: the case for person-centred care.

PMID- 25586747
TI  - Fostering early and mid-career research in affective disorders.

PMID- 25586748
TI  - Access to the internet in an acute child and adolescent mental health inpatient
      unit.

PMID- 25586749
TI  - Evolution of troponin, C-reactive protein and eosinophil count with the onset of
      clozapine-induced myocarditis.

PMID- 25586750
TI  - The role of anger and ongoing stressors in mental health following a natural
      disaster.
AB  - OBJECTIVE: Research has established the mental health sequelae following
      disaster, with studies now focused on understanding factors that mediate these
      outcomes. This study focused on anger, alcohol, subsequent life stressors and
      traumatic events as mediators in the development of mental health disorders
      following the 2009 Black Saturday Bushfires, Australia's worst natural disaster
      in over 100 years. METHOD: This study examined data from 1017 (M = 404, F = 613)
      adult residents across 25 communities differentially affected by the fires and
      participating in the Beyond Bushfires research study. Data included measures of
      fire exposure, posttraumatic stress disorder, depression, alcohol abuse, anger
      and subsequent major life stressors and traumatic events. Structural equation
      modeling assessed the influence of factors mediating the effects of fire exposure
      on mental health outcomes. RESULTS: Three mediation models were tested. The final
      model recorded excellent fit and observed a direct relationship between disaster
      exposure and mental health outcomes (b = .192, p < .001) and mediating
      relationships via Anger (b = .102, p < .001) and Major Life Stressors (b = .128,
      p < .001). Each gender was compared with multiple group analyses and while the
      mediation relationships were still significant for both genders, the direct
      relationship between exposure and outcome was no longer significant for men (p =
      .069), but remained significant (b = .234, p < .001) for women. CONCLUSIONS:
      Importantly, anger and major life stressors mediate the relationship between
      disaster exposure and development of mental health problems. The findings have
      significant implications for the assessment of anger post disaster, the provision
      of targeted anger-focused interventions and delivery of government and community
      assistance and support in addressing ongoing stressors in the post-disaster
      context to minimize subsequent mental health consequences.

PMID- 25586751
TI  - Eating behavior and obesity in bipolar disorder.
AB  - OBJECTIVES: Individuals with bipolar disorder are more frequently overweight or
      obese than the general population, but the reasons for this association are
      unknown. The aim of this study is to further understand the etiology of
      overweight and obesity in bipolar disorder. METHODS: We invited patients in a
      specialty outpatient bipolar clinic to complete the Eating Inventory. Patients
      provided self-reported restraint, disinhibition, and perceived hunger as well as
      general perceptions of dietary intake. RESULTS: Sixty-two individuals (37 female)
      between the ages of 18 and 67 (M = 41.5, SD = 13.38) and with an average body
      mass index (BMI) of 27.18 (SD = 5.71) completed the survey. Disinhibition and
      perceived hunger were positively correlated with BMI and self-reported difficulty
      eating healthy foods. Restraint was positively correlated with healthy eating (ps
      < .05). Stepwise linear regressions revealed that hunger was the most significant
      predictor of BMI (F(1) = 8.134, p = .006). Those participants with bipolar I or
      II disorder reported greater hunger scores (p < .01) and difficulty eating
      healthily (p < .05) than those without a full diagnosis. CONCLUSIONS: These
      results suggest that disinhibition and perception of hunger may be linked to the
      disproportionately high rate of obesity in bipolar disorder.

PMID- 25586752
TI  - Cardiovascular risk factor associations in adults with psychosis and adults in a
      national comparator sample.
AB  - OBJECTIVE: Antipsychotic drug treatment alters status on key risk factors for
      cardiovascular disease. The aim of this study was to test whether cardiovascular
      risk factor associations differ in adults with psychosis and adults from the
      general community. METHOD: Data were analysed for those aged 25-64 years from a
      nationally representative psychosis sample (n = 1,457) and a national comparator
      sample (n = 8,866). The Pearson correlation coefficient was used to estimate the
      association among tobacco use, body mass index, waist circumference, diastolic
      and systolic blood pressure and fasting total-, LDL- and HDL-cholesterol,
      triglycerides and plasma glucose. The robust Levene test was used to test for
      sample differences in variance. RESULTS: Correlations among cardiovascular risk
      indicators and between cardiovascular risk indicators and age were often
      significantly weaker in those with psychosis than in those from the national
      comparator sample. This was not due to a reduction in variance within the
      psychosis sample. CONCLUSIONS: Risk prediction that synthesizes multivariate risk
      indicator data needs to be connected to verified cardiovascular morbidity and
      mortality in those with psychosis to determine if standard risk calculators
      adequately discriminate those at high, medium and low future risk of
      cardiovascular morbidity and mortality. Until then the clinical implications of
      low or absent correlations among cardiovascular risk indicators and their low or
      absent association with increasing age is unclear but may indicate that risk
      equations commonly used in the general population may not be applicable for those
      with treated psychosis.

PMID- 25586753
TI  - The association between use of antidepressants and bone quality using
      quantitative heel ultrasound.
AB  - OBJECTIVE: Osteoporosis and depression are major public health problems
      worldwide. Studies have reported an association between antidepressant use,
      mainly selective serotonin reuptake inhibitors (SSRIs), and bone mineral density
      (BMD), but the issue remains unclear. METHODS: This study examined data collected
      from 849 Australian men (aged 24-98 years) participating in the Geelong
      Osteoporosis Study (GOS). Bone quality was determined using quantitative
      ultrasound (QUS) and included the following parameters: Broadband Ultrasound
      Attenuation (BUA), Speed of Sound (SOS) and Stiffness Index (SI). Anthropometry,
      socio-economic status (SES), medication use and lifestyle factors were
      determined. The cross-sectional associations between bone quality and use of
      antidepressants were studied using multivariate linear regression adjusted for
      potential confounders. RESULTS: At the time of assessment, 61 (7.2%) men were
      using antidepressants, of which 44 (72.1%) used SSRIs. Antidepressant use was
      associated with lower SI (p = .002), SOS (p = .010) and BUA (p = .053). However,
      body weight was identified as an effect modifier; QUS values were lower for
      antidepressant users with lower weight (< 90 kg) only. CONCLUSIONS: Use of
      antidepressants was associated with lower QUS values for men with low body
      weights. Thus, the risk of osteoporosis should be taken into account when
      prescribing antidepressants, in particular among men who are in this weight
      category.

PMID- 25586754
TI  - Treatment of postnatal depression with cognitive behavioural therapy, sertraline
      and combination therapy: a randomised controlled trial.
AB  - OBJECTIVES: Both antidepressant medications and psychological therapy are common
      treatments for depression in postpartum women. Antidepressant treatment may have
      a number of practical disadvantages, including a preference by women to avoid
      medication while breastfeeding. Consequently, more information about the relative
      benefits of the two modalities in the perinatal period is helpful. In the
      treatment of depressive disorders there is some evidence that combination
      therapies (pharmacological plus psychological treatment) may be more efficacious
      than either form of mono-therapy in isolation. However, in the treatment of
      postnatal depression, such evidence is limited. METHOD: Forty five postpartum
      women with a DSM-IV diagnosis of depression were randomised to receive either: 1)
      cognitive behavioural therapy (CBT); 2) sertraline, or 3) a combination of both
      treatment modalities. Psychometric measures were collected weekly for 12 weeks,
      with a follow-up at 24 weeks. RESULTS: Symptoms of depression and anxiety were
      reduced to a significant degree following all three treatments. CBT mono-therapy
      was found to be superior to both sertraline mono-therapy and combination therapy
      after 12 weeks. The CBT mono-therapy group appeared to display the most rapid
      initial gains after treatment commencement. CONCLUSIONS: In this sample, a
      specialised CBT program for postnatal depression was found to be superior as a
      mono-therapy compared to sertraline, a commonly prescribed SSRI antidepressant.
      This is in contrast to previous studies which have found no detectable difference
      in the efficacies of drug and psychological treatment for postnatal depression.
      Unlike some previous work, this study allowed a statistically independent
      evaluation of CBT mono-therapy for postnatal depression compared to both
      antidepressant and combination therapy. In line with previous studies in
      postpartum women, there was no detectable advantage of combining pharmacological
      and psychological treatments in the short term.

PMID- 25586755
TI  - The impact of premorbid adjustment, neurocognition, and depression on social and
      role functioning in patients in an early psychosis treatment program.
AB  - OBJECTIVE: Functional impairments are debilitating concomitants of psychotic
      disorders and are present early in the illness course and, commonly, prior to
      psychosis onset. The factors affecting social and role functioning in early
      psychosis (EP) following treatment are unclear. We evaluated whether six months
      of participation in the PREP(R), Boston, EP treatment program, part of a public
      academic community mental health center, was related to improvements in social
      and role functioning and whether premorbid adjustment in adolescence, baseline
      neurocognition, and depression symptoms predicted functional improvement. METHOD:
      The Global Functioning Social and Role scales, MATRICS neurocognitive battery,
      and Calgary Depression Scale were assessed at baseline and six months during
      naturalistic treatment, while premorbid adjustment was measured at baseline. All
      participants were psychotic disorder patients in PREP(R) (n = 46 with social
      functioning and 47 with role functioning measures at both time points). RESULTS:
      Large improvements were observed in role functioning (d = 0.84) and medium to
      large improvements were observed in social functioning (d = 0.70). Models
      consisting of adolescent premorbid adjustment and change in depression symptoms
      predicted social and role functioning change, whereas neuropsychological
      functioning did not. CONCLUSIONS: Substantial improvements in social and role
      functioning were observed among this sample participating in a recovery-based EP
      program. The impact of clinical factors on social and role functioning was
      highlighted. Further studies of premorbid adjustment in adolescence and the
      treatment of depression in EP programs in controlled treatment trials are needed
      to confirm these findings.

PMID- 25586756
TI  - What if nutrients could treat mental illness?

PMID- 25586757
TI  - Could modafinil be a drug of dependence?

PMID- 25586758
TI  - Is it time to update societal value sets for preference-based measures of health?

PMID- 25586760
TI  - Vertebroplasty in a 10-year-old boy with Gorham-Stout syndrome.
AB  - PURPOSE: To describe our experience using balloon vertebroplasty with
      polymethylmethacrylate filler in a 10-year-old boy with Gorham-Stout syndrome.
      Gorham-Stout syndrome is a rare disorder of unknown etiology characterized by
      intraosseous proliferation of fibrovascular or lymphatic tissue that results in
      progressive osteolysis and bone destruction. It can affect any part of the
      skeleton and lead to pathological fractures and muscular weakness or atrophy. The
      literature contains few reports on the surgical management of vertebral
      osteolysis with risk of fracture in children. Spinal fusion is the treatment of
      choice. METHODS: The patient was asymptomatic until age 10 years, when he began
      to experience back pain. Annual magnetic resonance scans did not show progression
      of bone disease. Medical treatment was unsuccessful, and the visual analog scale
      (VAS) for lumbar back pain was 8-10. Balloon vertebroplasty with
      polymethylmethacrylate filler was performed at L3 and L4, the vertebrae with an
      increased risk of pathological fracture. RESULTS: The postoperative course was
      uneventful. One month after surgery the VAS was 2-3. Four years later, the
      patient remains free of procedure-related complications, his clinical situation
      is stable, and no further low back pain has been reported. CONCLUSIONS: We report
      the only application to date of vertebroplasty to treat vertebral osteolysis in a
      pediatric patient. The outcome and possible complications of this technique
      remain unknown in children. The patient in the present report underwent
      vertebroplasty at two levels, and his progress remains satisfactory 4 years after
      surgery. He has not developed technical complications or changes in spinal
      growth. Therefore, we propose vertebroplasty for the treatment of vertebral
      osteolysis in pediatric patients at risk of pathological fracture.

PMID- 25586759
TI  - IPD without bony decompression versus conventional surgical decompression for
      lumbar spinal stenosis: 2-year results of a double-blind randomized controlled
      trial.
AB  - PURPOSE: Interspinous process devices (IPDs) are implanted to treat patients with
      intermittent neurogenic claudication (INC) based on lumbar spinal stenosis. It is
      hypothesized that patients with lumbar spinal stenosis treated with IPD have a
      faster short-term recovery, an equal outcome after 2 years and less back pain
      compared with bony decompression. METHODS: A randomized design with variable
      block sizes was used, with allocations stratified according to center.
      Allocations were stored in prepared opaque, coded and sealed envelopes, and
      patients and research nurses were blind throughout the follow-up. Five
      neurosurgical centers (including one academic and four secondary level care
      centers) included participants. 211 participants were referred to the Leiden-The
      Hague Spine Prognostic Study Group. 159 participants with INC based on lumbar
      spinal stenosis at one or two levels with an indication for surgery were
      randomized into two groups. Patients and research nurses were blinded for the
      allocated treatment throughout the study period. 80 participants received an IPD
      and 79 participants underwent spinal bony decompression. The primary outcome at
      long-term (2-year) follow-up was the score for the Zurich Claudication
      Questionnaire. Repeated measurement analyses were applied to compare outcomes
      over time. RESULTS: At two years, the success rate according to the Zurich
      Claudication Questionnaire for the IPD group [69 % (95 % CI 57-78 %)] did not
      show a significant difference compared with standard bony decompression [60 % (95
      % CI 48-71 %) p value 0.2]. Reoperations, because of absence of recovery, were
      indicated and performed in 23 cases (33 %) of the IPD group versus 6 (8 %)
      patients of the bony decompression group (p < 0.01). Furthermore, long-term VAS
      back pain was significantly higher [36 mm on a 100 mm scale (95 % CI 24-48)] in
      the IPD group compared to the bony decompression group [28 mm (95 % CI 23-34) p
      value 0.04]. CONCLUSIONS: This double-blinded study could not confirm the
      advantage of IPD without bony decompression over conventional 'simple'
      decompression, two years after surgery. Moreover, in the IPD treatment arm, the
      reoperation rate was higher and back pain was even slightly more intense compared
      to the decompression treatment arm.

PMID- 25586762
TI  - Enhanced thermoelectric performance of In2O3-based ceramics via Nanostructuring
      and Point Defect Engineering.
AB  - The issue of how to improve the thermoelectric figure of merit (ZT) in oxide
      semiconductors has been challenging for more than 20 years. In this work, we
      report an effective path to substantial reduction in thermal conductivity and
      increment in carrier concentration, and thus a remarkable enhancement in the ZT
      value is achieved. The ZT value of In2O3 system was enhanced 4-fold by
      nanostructuing (nano-grains and nano-inclusions) and point defect engineering.
      The introduction of point defects in In2O3 results in a glass-like thermal
      conductivity. The lattice thermal conductivity could be reduced by 60%, and
      extraordinary low lattice thermal conductivity (1.2 W m(-1) K(-1) @ 973 K) below
      the amorphous limit was achieved. Our work paves a path for enhancing the ZT in
      oxides by both the nanosturcturing and the point defect engineering for better
      phonon-glasses and electron-crystal (PGEC) materials.

PMID- 25586763
TI  - Are benzodiazepines and opioids really safe in patients with severe COPD?
AB  - Breathlessness is a key symptom in chronic obstructive pulmonary disease (COPD)
      with prognostic implications on health status and survival. Since most conditions
      underlying chronic refractory breathlessness in COPD are not modifiable, the use
      of opioids and benzodiazepines has been proposed to relieve it. However,
      respiratory depression is a known adverse event of these drugs, and concerns have
      been raised on their use in patients with chronic respiratory failure. Despite
      safety-related concerns, benzodiazepines are frequently prescribed for a variety
      of reasons, including treatment of insomnia, depression and anxiety, as well as
      to relieve refractory dyspnea in patients with COPD. The key role of opioids in
      the end-of-life and in the management of dyspnea that is unresponsive to best
      possible disease management is recognized. Moreover, the use of low dose opioids
      to treat dyspnea, discomfort or refusal for patient undergoing non-invasive
      ventilation is still debated. In the current review, we aim at discussing and
      analyzing recently published findings on the use of benzodiazepines and opioids
      in patients with COPD and at reviewing the literature on this topic. Recent
      observations favor the use of lower doses of opioids (<=30 mg oral morphine
      equivalents/day) for reduction of symptoms in those patients with severe COPD
      receiving long-term oxygen therapy. Low dose opioids are not associated with an
      increased risk of hospital admission or death in cohorts of COPD patients on long
      term oxygen therapy. On the contrary, benzodiazepines and opioids at higher doses
      might increase mortality. 

PMID- 25586761
TI  - Exercise training, creatine supplementation, and bone health in ovariectomized
      rats.
AB  - Evidence suggests that creatine may have some beneficial effects on bone. The
      study aimed to investigate the effects of exercise alone or combined with
      creatine on bone health in ovariectomized rats. Findings show that exercise, but
      not creatine, has an important role in improving bone health. INTRODUCTION: The
      aim of this study was to investigate the effects of exercise training alone or
      combined with creatine supplementation on bone health parameters in
      ovariectomized rats. METHODS: Wistar rats were randomly allocated into one of
      five groups: (i) sham-operated, (ii) ovariectomized non-trained placebo
      supplemented, (iii) ovariectomized non-trained creatine-supplemented, (iv)
      ovariectomized exercise-trained placebo-supplemented, and (v) ovariectomized
      exercise-trained creatine-supplemented. Downhill running training and/or creatine
      supplementation (300 mg/kg body weight) were administered for 12 weeks. Bone
      mineral content (BMC), bone mineral density (BMD), and biomechanical and
      histomorphometric parameters were assessed. RESULTS: No interaction effects were
      observed for BMC and BMD at whole body, femur, and lumbar spine (p > 0.05).
      Importantly, a main effect of training was detected for whole body BMC and BMD (p
      = 0.003 and p < 0.001, respectively), femoral BMC and BMD (p = 0.005 and p <
      0.001, respectively), and lumbar spine BMC and BMD (p < 0.001 and p < 0.001,
      respectively), suggesting that the trained animals had higher bone mass,
      irrespective of creatine supplementation. Main effects of training were also
      observed for maximal load (p < 0.001), stiffness (p < 0.001), and toughness (p =
      0.046), indicating beneficial effects of exercise training on bone strength.
      Neither a main effect of supplementation nor an interaction effect was detected
      for biomechanical parameters (p > 0.05). No main or interaction effects were
      observed for any of the histomorphometric parameters evaluated (p > 0.05).
      CONCLUSIONS: Exercise training, but not creatine supplementation, attenuated
      ovariectomy-induced bone loss in this rat model.

PMID- 25586764
TI  - Multi-platform lung tumors profiling identifies actionable targets and unveils
      series of uncommon/rare diseases.
AB  - Lung cancer is characterized by a number of genetic alterations, of which a
      proportion is still unknown. Nevertheless numerous pathogenetically important
      driver changes have been already been detected in a substantial fraction of
      patients and translated into a system to improve detection and outcome of the
      disease. In this scenario, the Lung Cancer Mutation Consortium developed an
      ambitious project aimed to perform on large scale the molecular profile of lung
      adenocarcinoma in order to identify actionable targets. The review analyses the
      paper - recently published showing study findings- taking into account if the car
      and not the driver matters in lung cancer precision management. 

PMID- 25586765
TI  - Spirometric criteria to diagnose airway obstruction in the elderly: fixed ratio
      vs lower limit of normal.
AB  - COPD is the most common chronic lung disease. It becomes more prevalent with
      increasing age but remains under-diagnosed in the elderly. A heated debate
      concerns the most suitable way to diagnose airway obstruction in this age group.
      Most COPD guidelines recommend to use a FEV1/FVC of 0.70 as threshold to define
      an obstructive ventilatory defect. While the use of a 0.70 ratio may be simple,
      it may result in under-diagnosis of airflow obstruction in young people and over
      diagnosis in the elderly due to an age-related decline in pulmonary volumes,
      especially in FEV1. This might lead to unnecessary use of medications and
      increased risk of adverse effects. A proposed strategy for reducing the
      misclassification of airway obstruction include the use of the statistically
      derived lower limit of normal (LLN) for FEV1/FVC, calculated as the fifth
      percentile of the normal distribution in a healthy population. Some authors
      addressed the possibility to evaluate lung function through high-resolution CT.
      In contrast to spirometry, CT imaging may allow for regional assessment of the
      compartments involved (airways, parenchyma, vasculature), and may enable a
      phenotype-driven characterization of COPD. Bhatt et al. recently observed that a
      small proportion (7%) of subjects with CT-defined emphysema were identified by
      the 0.70 threshold for FEV1/FVC but not by the LLN. However, there is no evidence
      that CT-emphysema corresponds to a clinical entity that can benefit by inhaled
      therapy. Further studies are needed to assess the classificatory and prognostic
      value of the different proposed criteria to diagnose airway obstruction in the
      elderly. 

PMID- 25586766
TI  - Erratum to: Single nucleotide polymorphism analysis of Korean native chickens
      using next generation sequencing data.

PMID- 25586767
TI  - Expression of genes related to mitochondrial function in Nellore cattle
      divergently ranked on residual feed intake.
AB  - Several measures have been proposed to investigate and improve feed efficiency in
      cattle. One of the most commonly used measure of feed efficiency is residual feed
      intake (RFI), which is estimated as the difference between actual feed intake and
      expected feed intake based on the animal's average live weight. This measure
      permits to identify and select the most efficient animals without selecting for
      higher mature weight. Mitochondrial function has been indicated as a major factor
      that influences RFI. The analysis of genes involved in mitochondrial function is
      therefore an alternative to identify molecular markers associated with higher
      feed efficiency. This study analyzed the expression of PGC1alpha, TFAM, UCP2 and
      UCP3 genes by quantitative real-time PCR in liver and muscle tissues of two
      groups of Nellore cattle divergently ranked on RFI values in order to evaluate
      the relationship of these genes with RFI. In liver tissue, higher expression of
      TFAM and UCP2 genes was observed in the negative RFI group. Expression of
      PGC1alpha gene did not differ significantly between the two groups, whereas UCP3
      gene was not expressed in liver tissue. In muscle tissue, higher expression of
      TFAM gene was observed in the positive RFI group. Expression of PGC1alpha, UCP2
      and UCP3 genes did not differ significantly between the two groups. These results
      suggest the use of TFAM and UCP2 as possible candidate gene markers in breeding
      programs designed to increase the feed efficiency of Nellore cattle.

PMID- 25586768
TI  - Intrinsic binding of 4-substituted-2,3,5,6-tetrafluorobenezenesulfonamides to
      native and recombinant human carbonic anhydrase VI.
AB  - Carbonic anhydrase (CA) VI is a potential drug target for cariogenesis and cancer
      of the salivary gland. It is the only secreted human CA isozyme which is found in
      saliva and milk. Here, CA VI was expressed in bacterial and mammalian cell
      cultures and directly affinity-purified from human saliva. The binding of 4
      substituted-2,3,5,6-tetrafluorobenezenesulfonamides to the native and recombinant
      CA VI from these three sources was compared. Interaction between the enzyme and
      inhibitors was determined by fluorescent thermal shift assay and isothermal
      titration calorimetry. The observed dissociation constants were the same within
      the error margin for all three CA VI preparations. The intrinsic binding
      parameters for the compounds were obtained by determining and dissecting the
      binding-linked protonation reactions. Intrinsic thermodynamic parameters of
      binding arrange the compounds in a buffer- and pH-independent manner. Intrinsic
      binding constants of nonfluorinated compounds were significantly stronger than
      those of fluorinated benzenesulfonamides. An opposite result was determined for
      the observed binding constants. The increase in observed affinity of the
      fluorinated compounds was due to the fluorine effect on diminishing the pKa of
      the compounds but not due to direct recognition of the protein. The temperature
      stability profiles for recombinant and native CA VI were compared and showed that
      CA VI is more stable in slightly acidic than neutral conditions. 

PMID- 25586769
TI  - Acupuncture provides short-term pain relief for patients in a total joint
      replacement program.
AB  - OBJECTIVE: Given the risks of opioid medications, nonpharmacological strategies
      should be considered for total joint replacement patients. We investigated
      acupuncture as an adjunct therapy for postsurgical pain management in a total
      joint replacement program by examining which total hip and knee replacement
      patients elected to receive acupuncture and the effect of acupuncture on short
      term pain. DESIGN: A total joint replacement program using fast-track
      physiotherapy offered elective postsurgical acupuncture to all patients, at no
      additional cost, as an adjunct therapy to opioids for pain management. SETTING:
      The Joint Replacement Center at Abbott Northwestern Hospital, a 630-bed teaching
      and specialty hospital in Minneapolis, Minnesota from 2010 to 2012. SUBJECTS: Our
      sample included 2,500 admissions of total hip (THR) and total knee replacement
      (TKR) patients. METHODS: Self-reported pain was assessed before and after
      acupuncture using a 0-10 scale and categorized as none/mild (0-4) and
      moderate/severe pain (5-10). RESULTS: Seventy-five percent of admissions included
      acupuncture. Women (Odds Ratio: 1.48, 95% Confidence Interval (CI): 1.22, 1.81)
      had higher odds of receiving acupuncture compared to men, and nonwhite patients
      (Odds Ratio: 0.55, 95% CI: 0.39, 0.78) had lower odds of receiving acupuncture
      compared to white patients. Average short-term pain reduction was 1.91 points
      (95% CI: 1.83, 1.99), a 45% reduction from the mean prepain score. Forty-one
      percent of patients reported moderate/severe pain prior to receiving acupuncture,
      while only 15% indicated moderate/severe pain after acupuncture. CONCLUSIONS:
      Acupuncture may be a viable adjunct to pharmacological approaches for pain
      management after THR or TKR.

PMID- 25586772
TI  - Effects of ultraviolet light (UV-C) and heat treatment on the quality of fresh
      cut Chokanan mango and Josephine pineapple.
AB  - The effects of ultraviolet (UV-C) and medium heat (70  degrees C) treatments on
      the quality of fresh-cut Chokanan mango and Josephine pineapple were
      investigated. Quality attributes included physicochemical properties (pH,
      titratable acidity, and total soluble solids), ascorbic acid content (vitamin C),
      antioxidant activity, as well as microbial inactivation. Consumers' acceptance
      was also investigated through sensory evaluation of the attributes (appearance,
      texture, aroma and taste). Furthermore, shelf-life study of samples stored at 4
      +/- 1  degrees C was conducted for 15 d. The fresh-cut fruits were exposed to UV
      C for 0, 15, 30, and 60 min while heat treatments were carried out at 70  degrees
      C for 0, 5, 10 and 20 min. Both UV-C and medium heat treatments resulted in no
      significant changes to the physicochemical attributes of both fruits. The
      ascorbic acid content of UV-C treated fruits was unaffected; however, medium heat
      treatment resulted in deterioration of ascorbic acids in both fruits. The
      antioxidants were enhanced with UV-C treatment which could prove invaluable to
      consumers. Heat treatments on the other hand resulted in decreased antioxidant
      activities. Microbial count in both fruits was significantly reduced by both
      treatments. The shelf life of the fresh-cut fruits were also successfully
      extended to a maximum of 15 d following treatments. As for consumers' acceptance,
      UV-C treated fruits were the most accepted as compared to their heat-treated
      counterparts. The results obtained through this study support the use of UV-C
      treatment for better retention of quality, effective microbial inactivation and
      enhancement of health promoting compounds for the benefit of consumers. 

PMID- 25586770
TI  - Magnetic resonance imaging and endorectal ultrasound for diagnosis of rectal
      lesions.
AB  - Endorectal ultrasonography (ERUS) and magnetic resonance imaging (MRI) allow
      exploring the morphology of the rectum in detail. Use of such data, especially
      assessment of the rectal wall, is an important tool for ascertaining the perianal
      fistula localization as well as stage of the cancer and planning it appropriate
      treatment, as stage T3 tumors are usually treated with neoadjuvant therapy,
      whereas T2 tumors are initially managed surgically. The only advantage of ERUS
      over MRI is the possibility of assessing T1 tumors that could be treated by
      transanal endoscopic microsurgery. However, MRI is better for visualizing most
      radiological prognostic features in rectal or anal cancer such as a
      circumferential resection margin less than 1 mm, T stage at T1-T2 or T3 tumors
      with extramural extension less than 5 mm, absence of extramural vascular
      invasion, N stage at N0/N1, and tumors located in the middle or upper third of
      the rectum. It can also evaluate the intersphincteric space or levator ani muscle
      involvement. Increased signal on diffusion weighted imaging (DWI) and low
      apparent diffusion coefficient (ADC) values as well as an irregular contour and
      heterogeneous internal signal intensity seem to predict the involvement of pelvic
      lymphatic nodes better than their size alone. Computed tomography as well as
      other examination techniques, including digital rectal examination, contrast
      edema, recto- and colonoscopy, are less useful in staging of rectal cancer but
      still are very important screening tools.

PMID- 25586773
TI  - In vitro hemodynamic evaluation of a novel pulsatile extracorporeal life support
      system: impact of perfusion modes and circuit components on energy loss.
AB  - The objective of this study is to investigate the impact of every component of
      extracorporeal life support (ECLS) circuit on hemodynamic energy transmission in
      terms of energy equivalent pressure (EEP), total hemodynamic energy (THE), and
      surplus hemodynamic energy (SHE) under nonpulsatile and pulsatile modes in a
      novel ECLS system. The ECLS circuit consisted of i-cor diagonal pump and console
      (Xenios AG, Heilbronn, Germany), an iLA membrane ventilator (Xenios AG), an 18 Fr
      femoral arterial cannula, a 23/25 Fr femoral venous cannula, and 3/8-in ID
      arterial and venous tubing. The circuit was primed with lactated Ringer's
      solution and human whole blood (hematocrit 33%). All trials were conducted under
      room temperature at the flow rates of 1-4 L/min (1 L/min increments). The
      pulsatile flow settings were set at pulsatile frequency of 75 beats per minute
      and differential speed values of 1000-4000 rpm (1000 rpm increments). Flow and
      pressure data were collected using a custom-based data acquisition system. EEP
      was significantly higher than mean arterial pressure in all experimental
      conditions under pulsatile flow (P < 0.01). THE was also increased under
      pulsatile flow compared with the nonpulsatile flow (P < 0.01). Under pulsatile
      flow conditions, SHE was significantly higher and increased differential rpm
      resulted in significantly higher SHE (P < 0.01). There was no SHE generated under
      nonpulsatile flow. Energy loss depending on the circuit components was almost
      similar in both perfusion modes at all different flow rates. The pressure drops
      across the oxygenator were 3.8-24.9 mm Hg, and the pressure drops across the
      arterial cannula were 19.3-172.6 mm Hg at the flow rates of 1-4 L/min. Depending
      on the pulsatility setting, i-cor ECLS system generates physiological quality
      pulsatile flow without increasing the mean circuit pressure. The iLA membrane
      ventilator is a low-resistance oxygenator, and allows more hemodynamic energy to
      be delivered to the patient under pulsatile mode. The 18 Fr femoral arterial
      cannula has acceptable pressure drops under nonpulsatile and pulsatile modes.
      Further in vivo studies are warranted to confirm these results. 

PMID- 25586774
TI  - Hookah Use Predicts Cigarette Smoking Progression Among College Smokers.
AB  - INTRODUCTION: Hookah use is increasingly common among U.S. college students, but
      little is known regarding the relationship between hookah and cigarette use. The
      purpose of this study was to test the hypothesis that the added nicotine exposure
      from hookah use may accelerate the uptake of cigarettes. METHODS: An ethnically
      diverse sample of college students (n = 256; 43% female) who had smoked
      cigarettes in the past month completed 2 in-person interviews over 6 months. This
      study was a secondary analysis of data collected for a longitudinal study of
      young adult cigarette smoking patterns. Analyses examined 6-month changes in past
      30 day cigarettes smoked and number of days smoking, controlling for age,
      nicotine dependence, marijuana use, and the respective baseline variable for each
      outcome. RESULTS: Current hookah use (any use in past 30 days) was endorsed by
      34% of participants at baseline, while 94% reported lifetime use. Change in past
      30 day number of cigarettes (p = .043) and number of smoking days (p = .040)
      differed significantly between those who did or did not report recent hookah use
      at baseline. Hookah users reported a greater number of cigarettes smoked at the 6
      month follow-up, while nonusers decreased their smoking quantity. For number of
      smoking days in the past 30, hookah users reported a smaller decrease than
      nonusers. CONCLUSIONS: Recent hookah use predicted increased cigarette smoking
      over 6 months in a college sample. These are the first prospective data
      demonstrating this relationship, indicating the value of developing strategies to
      prevent hookah use among college students.

PMID- 25586771
TI  - Special AT-rich sequence-binding protein-1 participates in the maintenance of
      breast cancer stem cells through regulation of the Notch signaling pathway and
      expression of Snail1 and Twist1.
AB  - The stem cell populations in cancerous tissues and cell lines vary widely and are
      often associated with aggressive cases of breast cancer. Despite research on the
      topic, the mechanism underlying the regulation of the breast cancer stem cell
      (BCSC) population within tumors remains to be fully elucidated. To investigate
      the function of special AT-rich sequence-binding protein-1 (SATB1) in the
      maintenance of the BCSC population, SATB1 was overexpressed with lentivirus in
      MCF-7 cells or knocked down with shRNA-lentivirus in BT-549 cells. The effects of
      SATB1 overexpression or knockdown on mammosphere formation, the size of the of
      BCSC population, cell invasion and tumorigenesis were investigated. Activation of
      the Notch signaling pathway and expression of Snail1 and Twist1 were also
      examined in the cells. Overexpression of SATB1 in MCF-7 cells was observed to
      increase mammosphere formation, the size of the BCSC population, cell invasion
      and tumorigenesis, accompanied by an increase in the activation of Notch
      signaling and expression levels of Snail1 and Twist1. Conversely, knockdown of
      SATB1 in BT-549 cells produced the opposite effects. The results indicated that
      expression of SATB1 may increase the size of the BCSC population via the
      activation of the Notch signaling pathway and by increasing expression levels of
      Snail1 and Twist1.

PMID- 25586775
TI  - Economic Impact of Smoke-Free Legislation: Did the Spanish Tobacco Control Law
      Affect the Economic Activity of Bars and Restaurants?
AB  - INTRODUCTION: The potential of smoke-free bans to negatively impact the
      hospitality business has been an argument of the hospitality and tobacco industry
      against such legislation. A partial smoke-free legislation was introduced in
      Spain in 2006 allowing smoking in most bars and restaurants due to the pressure
      of the hospitality sector. However, this partial ban was later amended in 2011 to
      include all the hospitality premises without exceptions. The stepped Spanish
      process permits to evaluate whether the entry into force of the smoke-free
      legislation had any effect on the economic activity of the hospitality sector.
      METHODS: We employed a pooled time series cross-sectional design, with national
      data over 6 years (2006-2011). The dependent variable used was the total number
      of bars and restaurants per 100,000 inhabitants. The explanatory variables used
      were the average amount of spending per household in bars and restaurants, and
      the total unemployment rate in Spain by regions. RESULTS: For every 1% increase
      in the unemployment rate there was a 0.05% decrease in the number of bars and
      restaurants. In 2007, the number of bars and restaurants was significantly
      reduced by 13.06% (all others factors being held constant), 4.87% in 2008, and
      10.42% in 2009. No statistically significant effect of the smoke-free legislation
      emerged from 2010 (6.76%) to 2011 (7.69%). CONCLUSION: The new Spanish smoke-free
      legislation had no effect on the number of bars and restaurants.

PMID- 25586776
TI  - The Association Between Tobacco Control Policy and Educational Inequalities in
      Smoking Cessation in the Netherlands from 1988 Through 2011.
AB  - INTRODUCTION: Tobacco control policies seemed to have failed to reduce
      socioeconomic inequalities in smoking in the past. It has been argued that a
      comprehensive mix of policies is needed. Our aim was to assess whether tobacco
      control policy development in the Netherlands between 1988 and 2011 was
      associated with educational inequalities in smoking cessation and cigarette
      consumption. METHODS: Data were derived from the cross-sectional Dutch Continuous
      Survey of Smoking Habits, with a study sample of 259,140 respondents from 1988
      through 2011. Outcomes were the quit ratio and mean number of cigarettes smoked
      per day. The determinant was the Tobacco Control Scale (TCS). We used multilevel
      logistic regression modeling, with years, quarters, and individuals as levels,
      and controlled for sex, age, and time. RESULTS: A significant association between
      the TCS and smoking cessation was found in 2001-2011, but not in 1988-2000.
      Associations for low- and high-education groups were similar (OR = 1.23; 95% CI =
      1.12-1.34 and OR = 1.17; 95% CI = 1.03-1.32 respectively). The TCS was not
      significantly associated with the number of cigarettes smoked per day for either
      the low- or high-education groups (B = -0.09; 95% CI = -0.46-0.27 and B = -0.59;
      95% CI = -1.24-0.06 respectively). CONCLUSIONS: Strong tobacco control policies
      introduced in the Netherlands after 2000 were positively associated with national
      trends in smoking cessation, whereas weaker policies introduced gradually before
      2000 were not. However, these measures do not seem to have either widened or
      narrowed educational inequalities in smoking cessation rates-both groups
      benefitted about equally.

PMID- 25586777
TI  - Comment on Farsalinos et al., "Evaluation of Electronic Cigarette Liquids and
      Aerosol for the Presence of Selected Inhalation Toxins".

PMID- 25586778
TI  - Why We Consider the NIOSH-Proposed Safety Limits for Diacetyl and Acetyl
      Propionyl Appropriate in the Risk Assessment of Electronic Cigarette Liquid Use:
      A Response to Hubbs et al.

PMID- 25586779
TI  - Clinical effectiveness and safety of vildagliptin in >19 000 patients with type 2
      diabetes: the GUARD study.
AB  - The present GUARD study was a prospective, non-interventional study evaluating
      the clinical effectiveness, safety and tolerability of vildagliptin with or
      without metformin in adult patients with type 2 diabetes mellitus (T2DM) studied
      in routine clinical practice. Patients were enrolled from countries across four
      geographical regions. The primary endpoint was change in glycated haemoglobin
      (HbA1c) concentration from baseline after 24 weeks of treatment with vildagliptin
      with or without metformin. Of 19 331 patients analysed, 3511 received
      vildagliptin and 15 820 received vildagliptin plus metformin. At week 24, the
      mean HbA1c was reduced significantly from baseline by -1.27% (vildagliptin: 
      1.17%; vildagliptin plus metformin: -1.29%; p < 0.0001). Significant reductions
      in HbA1c from baseline were consistently reported regardless of patient age, body
      mass index (BMI) or baseline HbA1c. Weight and BMI were also significantly
      reduced from baseline. Vildagliptin treatment with or without metformin was
      generally well tolerated. It provided clinically relevant glycaemic and weight
      control, and was well tolerated in a large multi-ethnic population of patients
      with T2DM studied in routine clinical practice. 

PMID- 25586781
TI  - Low serum tryptophan predicts higher mortality in cardiovascular disease.
AB  - BACKGROUND: The essential amino acid tryptophan is required for protein synthesis
      and formation of the neurotransmitter serotonin and may exert immunoregulatory
      functions. An accelerated tryptophan breakdown rate is associated with
      inflammation and immune activation. MATERIALS AND METHODS: Serum concentrations
      of free tryptophan, neopterin and high-sensitivity C-reactive protein (hsCRP)
      were measured in 1196 patients with coronary artery disease (CAD) derived from
      the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. RESULTS:
      Tryptophan concentrations did not differ between patients with (mean +/- SD: 40.1
      +/- 9.8 MUM) or without (42.3 +/- 23.9 MUM; not significant, Welch's test)
      angiographic CAD, but patients with CAD had higher neopterin (9.1 +/- 8.2 nM) and
      hsCRP (9.3 +/- 18.5 mg/L) concentrations compared to patients without (neopterin:
      7.6 +/- 4.7 nM, hsCRP: 5.8 +/- 7.6 mg/L; both P < 0.0001). There existed an
      inverse correlation between serum tryptophan and neopterin (Spearman's rank
      correlation: rs = -0.273) and hsCRP (rs = -0.163; both P < 0.0001)
      concentrations. Median observation time was 10.5 years, and 385 patients had
      died, including 244 patients due to cardiovascular and 132 due to
      noncardiovascular causes. After adjustments for cardiovascular risk factors and
      other possible confounders, the hazard ratio (with 95% CI) in the first
      tryptophan quartile of the study population was 1.51 (1.19-1.90; P = 0.0006) for
      total mortality, 1.41 (1.05-1.89; P = 0.0224) for cardiovascular and 1.79 (1.20
      2.67; P = 0.0042) for noncardiovascular mortalities, respectively, thus
      indicating a significantly higher risk of death in patients with tryptophan
      concentrations < 34 MUM. CONCLUSIONS: Low serum tryptophan in patients with CAD
      is associated with immune activation and indicates reduced life expectancy.

PMID- 25586780
TI  - Co-immunization with DNA and protein mixture: a safe and efficacious
      immunotherapeutic strategy for Alzheimer's disease in PDAPP mice.
AB  - Active immunotherapy targeting beta-amyloid (Abeta) is the most promising
      strategy to prevent or treat Alzheimer's disease (AD). Based on pre-clinical
      studies and clinical trials, a safe and effective AD vaccine requires a delicate
      balance between providing therapeutically adequate anti-Abeta antibodies and
      eliminating or suppressing unwanted adverse T cell-mediated inflammatory
      reactions. We describe here the immunological characterization and protective
      efficacy of co-immunization with a 6Abeta15-T DNA and protein mixture without
      adjuvant as an AD immunotherapeutic strategy. Impressively, this co-immunization
      induced robust Th2-polarized Abeta-specific antibodies while simultaneously
      suppressed unwanted inflammatory T cell reactions and avoiding Abeta42-specific T
      cell-mediated autoimmune responses in immunized mice. Co-immunization with the
      DNA + protein vaccine could overcome Abeta42-associated hypo-responsiveness and
      elicit long-term Abeta-specific antibody responses, which helped to maintain
      antibody-mediated clearance of amyloid and accordingly alleviated AD symptoms in
      co-immunized PDAPP mice. Our DNA and protein combined vaccine, which could induce
      an anti-inflammatory Th2 immune response with high level Abeta-specific
      antibodies and low level IFN-gamma production, also demonstrated the capacity to
      inhibit amyloid accumulation and prevent cognitive dysfunction. Hence, co
      immunization with antigen-matched DNA and protein may represent a novel and
      efficacious strategy for AD immunotherapy to eliminate T cell inflammatory
      reactions while retaining high level antibody responses. 

PMID- 25586782
TI  - Evolutionary forward genomics reveals novel insights into the genes and pathways
      dysregulated in recurrent early pregnancy loss.
AB  - STUDY QUESTION: Are the genes that gained novel expression in the endometria of
      Eutherian (placental) mammals more likely to be dysregulated in patients with
      endometrial-associated recurrent early pregnancy loss (REPL)? SUMMARY ANSWER:
      There was a significant enrichment of genes dysregulated in REPL patients among
      the Eutherian-specific endometrial genes. WHAT IS KNOWN ALREADY: Pregnancy loss
      is the most common complication of human pregnancy. REPL has multiple etiologies,
      including dysregulation of endometrial function, leading to 'suboptimal'
      implantation. Although the implantation process is tightly regulated in Eutherian
      (placental) mammals, the molecular factors contributing to dysregulated
      endometrial gene expression patterns in women with REPL are largely unknown.
      STUDY DESIGN, SIZE, DURATION: Endometrial biopsies were obtained from 32 REPL
      patients during the mid-luteal phase, and evaluated for glandular development
      arrest based on elevated nuclear cyclin E levels in gland cells, and for out-of
      phase endometrial development based on histology. Gene expression levels were
      measured using Illumina Human HT-12v4 BeadChip arrays. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Differentially expressed genes were identified between patients
      with (i) out-of-phase (n = 10) versus normal (n = 22) histological dating and
      (ii) abnormally elevated (n = 9) versus normal (n = 23) cyclin E levels in the
      nuclei of endometrial glands, using a likelihood ratio test. Enrichment of
      dysregulated genes in REPL endometria among Eutherian-specific genes was tested
      by permutation. Gene ontology and pathway enrichment analyses were carried out
      for the dysregulated genes. MAIN RESULTS AND THE ROLE OF CHANCE: Fifty-eight and
      eighty-one genes were identified as differentially expressed at P < 0.001 in
      women with out-of-phase histological dating and abnormally elevated glandular
      cyclin E levels, respectively. Genes that were recruited into endometrial
      expression during the evolution of pregnancy in Eutherian mammals were
      significantly enriched for dysregulated genes (P = 0.002 for histology, P = 0.021
      for cyclin E), as well as for genes involved in immune response and signaling
      pathways with essential roles in implantation and endometrial biology.
      LIMITATIONS, REASONS FOR CAUTION: Small sample size limits the statistical power
      to detect dysregulated genes, and the lack of non-REPL control women does not
      allow us to test for the contribution of these genes to overall risk of REPL.
      WIDER IMPLICATIONS OF THE FINDINGS: Enrichment of functional gene categories, as
      well as genes gained expression in the Eutherian endometria, help to identify
      molecular etiologies that contribute to normal functioning of the endometrium.
      These pathways are also strong candidates for successful pregnancy outcomes.
      Using the evolutionary history of mammalian gene expression in the endometrial
      tissue may be a promising approach to discover genes involved in female
      reproductive disorders. STUDY FUNDING/COMPETING INTERESTS: This work is supported
      by National Institutes of Health (NIH) grant R01 HD21244 to C.O. Authors declare
      no competing interests.

PMID- 25586783
TI  - Follicle pool, ovarian surgery and the risk for a subsequent trisomic pregnancy.
AB  - STUDY QUESTION: Is there an association between trisomic pregnancy, a marker for
      decreased oocyte quality, and the reduced oocyte quantity that follows ovarian
      surgery? SUMMARY ANSWER: Previous ovarian surgery is not associated with an
      increased risk for a subsequent trisomic pregnancy. WHAT IS KNOWN ALREADY:
      Ovarian surgery diminishes the number of oocytes. The risk for a trisomic
      pregnancy is suggested to be higher in women with fewer oocytes, independent of
      their chronological age. STUDY DESIGN, SIZE, DURATION: This is a matched case
      control study. Cases are women with a confirmed trisomic pregnancy occurring
      between 1 January 2000 and 31 December 2010 regardless of pregnancy outcome and
      controls are women that had a live born child without a trisomy. In total, there
      were 8573 participants in the study; 1723 cases and 6850 controls.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were obtained from Danish medical
      registries. Matching criteria were maternal age and year of conception. Number of
      controls matched per case ranged from one to four. Among cases and controls with
      a trisomic pregnancy, 2.7% (46/1723) versus 2.5% (172/6850) had undergone ovarian
      surgery before pregnancy. MAIN RESULTS AND ROLE OF CHANCE: History of ovarian
      surgery is not associated with a higher risk for a subsequent trisomic pregnancy
      (odds ratio = 1.00, 95% confidence interval 0.99-1.01). Subgroup analyses by
      indication of surgery and interval between ovarian surgery and pregnancy do not
      show an effect on trisomic pregnancy risk. LIMITATIONS, REASONS FOR CAUTION: The
      medical registries used to select cases and controls did not contain information
      on surgical technique nor volume of ovarian tissue resected, previous trisomic
      pregnancy prior to the ovarian surgery or long-term use of oral contraceptives.
      Therefore, correction for these factors was not performed. WIDER IMPLICATIONS OF
      THE FINDINGS: We did not confirm the hypothesis that ovarian surgery, a marker
      for decreased oocyte quantity, is related to trisomic pregnancy, a marker for
      decreased oocyte quality. This suggests that ovarian surgery, which has a direct
      reductive effect on the size of the follicle pool, may affect oocyte quality
      differently when compared with the reduction in follicle pool size due to ageing.
      STUDY FUNDING/COMPETING INTERESTS: The study was supported by grants from the
      Gratama Stichting, University of Groningen and the University Medical Center
      Groningen, The Netherlands. O.L. has within the last 3 years received honoraria
      for speeches in pharmacoepidemiological issues, not related to this study. The
      Department of Obstetrics and Gynaecology receives unrestricted educational grants
      from Ferring Pharmaceuticals. A.H. received a grant from ZonMW (i.e. National
      Dutch Scientific funding) for a RCT not related to this publication. Dr A.H.
      received speakers fee from MSD for an educational presentation. All other authors
      have no conflict of interest.

PMID- 25586784
TI  - Polycystic ovary syndrome susceptibility single nucleotide polymorphisms in women
      with a single PCOS clinical feature.
AB  - STUDY QUESTION: What is the direct genetic contribution of the polycystic ovary
      syndrome (PCOS) susceptibility single nucleotide polymorphisms (SNPs), identified
      by previous genome-wide association studies (GWAS) to the definitive clinical
      features of the syndrome? SUMMARY ANSWER: Each single PCOS clinical feature had a
      specific genetic association, and rs4385527 in the chromosome 9 open reading
      frame 3 (C9orf3) conferred a particular risk to the three defined PCOS clinical
      features in this study, which suggested its fundamental role in the etiology of
      PCOS. WHAT IS KNOWN ALREADY: PCOS is a heterogeneous disorder characterized by
      anovulation (OA), hyperandrogenism (HA) and polycystic ovary morphology (PCOM).
      Two previous GWAS in China have identified 15 independent susceptibility SNPs
      related to PCOS (PCOS-SNPs). However, little is known about the candidate gene of
      each clinical feature. STUDY DESIGN, SIZE, DURATION: Case-control study. Three
      independent groups of women were recruited from 2010 to 2012: 746 subjects with
      OA only, 278 subjects with HA only and 536 subjects with PCOM only. A total of
      1790 healthy women with none of the above pathological characteristics were also
      enrolled as control subjects during the same time period. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: All participants were women of reproductive age. Genotype and
      allelic frequencies of 15 PCOS-SNPs were determined in all subjects using direct
      sequencing and Sequenom Arrays. The allelic frequencies of each case group were
      compared with the controls. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment
      for age and BMI, variants in luteinizing hormone/choriogonadotropin receptor
      (LHCGR) (rs13405728), C9orf3 (rs4385527) and insulin receptor gene (INSR)
      (rs2059807) were strongly associated with OA (Padjust < 0.01, <0.001 and <0.05,
      respectively); rs4385527 in C9orf3 was strongly associated with HA (Padjust<
      0.001); variants in the thyroid adenoma associated gene (THADA) (rs13429458 and
      rs12478601), DENN/MADD domain containing 1A (DENND1A)(rs10818854), and C9orf3
      (rs4385527) were significantly associated with PCOM (Padjust < 0.01, <0.001,
      <0.05 and <0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: The sample
      size of some case groups was relatively small, which therefore limited the
      statistical power of the analysis to a certain extent. WIDER IMPLICATIONS OF THE
      FINDINGS: The present study indicates a potential common genetic basis of three
      PCOS clinical features. Other specific associated genes may play a synergistic
      role, leading to heterogeneous pathophysiological changes. Additionally, the
      increased frequency of PCOS-risk alleles in women with single PCOS clinical
      features suggests that these subjects have an elevated risk of developing the
      syndrome, although they cannot be currently diagnosed. STUDY FUNDING/COMPETING
      INTERESTS: This research was supported by the National Basic Research Program of
      China (973 Program) (2012CB944700, 2011CB944502), the National Key Technology
      Research and Development Program(2011BAI17B00), the National Natural Science
      Foundation of China (81430029, 81201441, 81490743, 31371453), the Scientific
      Research Foundation of Shandong Province of Outstanding Young Scientist
      (2012BSE27089) and the Fundamental Research Funds of Shandong
      University(2014GN025). There were no competing interests.

PMID- 25586785
TI  - Histological evaluation of ureteral involvement in women with deep infiltrating
      endometriosis: analysis of a large series.
AB  - STUDY QUESTION: In women with deeply infiltrating endometriosis (DIE) what is the
      prevalence of involvement of endometriotic tissue and fibrosis in ureteral
      endometriosis (UE), as assessed by histological staining? SUMMARY ANSWER: In
      women with DIE, ureteral involvement is more often due to endometriotic tissue
      rather than fibrosis. WHAT IS KNOWN ALREADY: In the current literature,
      histological evaluation of ureteral endometriosis is mainly based on the degree
      of wall infiltration by endometriosis instead of the tissue composition. A few
      studies reported ill-defined and contradictory histological data on the tissue
      composition of UE. STUDY DESIGN, SIZE, DURATION: Retrospective observational
      study based on clinical records of women affected by DIE, laparoscopically
      treated for UE at a tertiary referral center, between January 2010 and March
      2013. All cases of ureteral nodule excision or ureterectomy with histological
      examination of the specimens were included. Exclusion criteria were other
      identified causes of hydroureteronephrosis, medical therapy for a period of at
      least 3 months before surgery and previous surgery for DIE.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 77 patients were included in
      the study and among them seven (9%) presented with bilateral ureteral
      involvement, giving a total of 84 cases of UE available for analysis. All
      patients had stage IV endometriosis. According, respectively, to the presence of
      endometrial glands and/or stroma cells or of fibrotic tissue only, the
      endometriotic UE and fibrotic UE groups were compared with regard to
      hydroureteronephrosis at pre-operative urinary tract computerized tomography
      scan, type of surgical procedure performed to treat UE (nodule removal or
      ureterectomy), association with other locations of the disease and post-operative
      complications (ureteral fistula or stenosis). MAIN RESULTS AND THE ROLE OF
      CHANCE: For the 84 cases of UE, 65 (77%) and 19 (23%), respectively, showed
      endometriotic tissue and fibrotic tissue only. Presence of hydroureteronephrosis
      and endometriotic pattern of UE showed a significant association [endometriotic
      UE 44/65 (68%) versus fibrotic UE 8/19 (42%); P = 0.04]. Fibrotic pattern of UE
      and presence of concomitant recto-vaginal endometriosis showed a significant
      association [endometriotic group: 29/65 (45%) versus fibrotic group 18/19 (95%);
      P < 0.001]. LIMITATIONS, REASONS FOR CAUTION: The retrospective and monocentric
      (tertiary referral center) study design. WIDER IMPLICATIONS OF THE FINDINGS:
      Besides the distinction between extrinsic and intrinsic UE based on the degree of
      wall infiltration by endometriosis, a new classification according to the
      histological pattern of UE could be useful for clinicians, both in the diagnostic
      and therapeutic fields. STUDY FUNDING/COMPETING INTERESTS: None.

PMID- 25586787
TI  - Estimating the net effect of progesterone elevation on the day of hCG on live
      birth rates after IVF: a cohort analysis of 3296 IVF cycles.
AB  - STUDY QUESTION: What is the proper way of assessing the effect of progesterone
      elevation (PE) on the day of hCG on live birth in women undergoing fresh embryo
      transfer after in vitro fertilization (IVF) using GnRH analogues and
      gonadotrophins? SUMMARY ANSWER: This study indicates that a multivariable
      approach, where the effect of the most important confounders is controlled for,
      can lead to markedly different results regarding the association between PE on
      the day of hCG and live birth rates after IVF when compared with the bivariate
      analysis that has been typically used in the relevant literature up to date. WHAT
      IS KNOWN ALREADY: PE on the day of hCG is associated with decreased pregnancy
      rates in fresh IVF cycles. Evidence for this comes from observational studies
      that mostly failed to control for potential confounders. STUDY DESIGN, SIZE,
      DURATION: This is a retrospective analysis of a cohort of fresh
      IVF/intracytoplasmic sperm injection cycles (n = 3296) performed in a single IVF
      centre during the period 2001-2013. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Patients in whom ovarian stimulation was performed with gonadotrophins and GnRH
      analogues. Natural cycles and cycles where stimulation involved the
      administration of clomiphene were excluded. In order to reflect routine clinical
      practice, no other exclusion criteria were imposed on this dataset. The primary
      outcome measure for this study was live birth defined as the delivery of a live
      infant after 24 weeks of gestation. We compared the association between PE on the
      day of hCG (defined as P > 1.5 ng/ml) and live birth rates calculated by simple
      bivariate analyses with that derived from multivariable logistic regression. The
      multivariable analysis controlled for female age, number of oocytes retrieved,
      number of embryos transferred, developmental stage of embryos at transfer
      (cleavage versus blastocyst), whether at least one good-quality embryo was
      transferred, the woman's body mass index, the total dose of FSH administered
      during ovarian stimulation and the type of GnRH analogues used (agonists versus
      antagonists) during ovarian stimulation. In addition, an interaction analysis was
      performed in order to assess whether the ovarian response (<6, 6-18, >18 oocytes)
      has a moderating effect on the association of PE on the day of hCG with live
      birth rates after IVF. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth rates were
      not significantly different between cycles with and those without PE when a
      bivariate analysis was performed [odds ratio (OR): 0.78, 95% confidence interval
      (CI): 0.56-1.09]. However, when a multivariable analysis was performed,
      controlling for the effect of the aforementioned confounders, live birth rates
      (OR: 0.68, 95% CI: 0.48-0.97) were significantly decreased in the group with PE
      on the day of hCG. The number of oocytes retrieved was the most potent
      confounder, causing a 29.4% reduction in the OR for live birth between the two
      groups compared. Furthermore, a moderating effect of ovarian response on the
      association between PE and live birth rates was not supported in the present
      analysis since no interaction was detected between PE and the type of ovarian
      response (<6, 6-18, >18 oocytes). LIMITATIONS, REASONS FOR CAUTION: This is a
      retrospective analysis of data collected during a 12-year period, and although
      the effect of the most important confounders was controlled for in the
      multivariable analysis, the presence of residual bias cannot be excluded. WIDER
      IMPLICATIONS OF THE FINDINGS: This analysis highlights the need for a
      multivariable approach when researchers or clinicians aim to evaluate the impact
      of PE on pregnancy rates in their own clinical setting. Failure to do so might
      explain why many past studies have failed to identify the detrimental effect of
      PE in fresh IVF cycles. STUDY FUNDING/COMPETING INTERESTS: None.

PMID- 25586786
TI  - Differentiation of primordial germ cells from induced pluripotent stem cells of
      primary ovarian insufficiency.
AB  - STUDY QUESTION: Can the induced pluripotent stem cells (iPSCs) derived from women
      with primary ovarian insufficiency (POI) differentiate into germ cells for
      potential disease modeling in vitro? SUMMARY ANSWER: The iPSC lines derived from
      POI patients with 46, X, del(X)(q26) or 46, X, del(X)(q26)9qh+ could
      differentiate into germ cells and expressed lower levels of genes in the deletion
      region of the X chromosome. WHAT IS KNOWN ALREADY: iPSC technology has been
      envisioned as an approach for generating patient-specific stem cells for disease
      modeling and for developing novel therapies. It has also been confirmed that
      iPSCs differentiate into germ cells. STUDY DESIGN, SIZE, DURATION: We compared
      the differentiation ability of germ cells and the gene expression level of germ
      cell-related genes in the X chromosome deletion region of iPSC lines derived from
      POI patients (n = 2) with an iPSC line derived from normal fibroblasts (n = 1).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: We established three iPSC lines from
      two patients with partial Xq deletion-induced POI and normal fibroblasts by
      overexpressing four factors: octamer-binding transcription factor 4 (OCT4), sex
      determining region Y-box 2 (SOX2), Nanog homeobox (NANOG), and lin-28 homolog
      (LIN28), using lentiviral vectors. We then generated stable-transfected
      fluorescent reporter cell lines under the control of the Asp-Glu-Ala-Asp box
      polypeptide 4 (DDX4, also called VASA) promoter, and selected clonal derived
      sublines. We induced subline differentiation into germ cells by adding Wnt3a (30
      ng/ml) and bone morphogenetic protein 4 (100 ng/ml). After 12 days of
      differentiation, green fluorescent protein (GFP)-positive and GFP-negative cells
      were isolated via fluorescence-activated cell sorting and analyzed for endogenous
      VASA protein (immunostaining) and for germ cell markers and genes expressed in
      the deleted region of the X chromosome (quantitative RT-PCR). MAIN RESULTS AND
      THE ROLE OF CHANCE: The POI- and normal fibroblast-derived iPSCs had typical self
      renewal and pluripotency characteristics. After stable transfection with the VASA
      GFP construct, the sublines POI1-iPS-V.1, POI2-iPS-V.1 and hEF-iPS-V.1 produced
      green fluorescent cells in the differentiated cultures, and the percentage of GFP
      positive cells increased over the 12 days of differentiation to a maximum of 6.9
      +/- 0.33%, 5.3 +/- 0.57% and 8.5 +/- 0.29%, respectively, of the total cell
      population. Immunohistochemical analysis confirmed that endogenous VASA was
      enriched in the GFP-positive cells. Quantitative reverse transcription-PCR
      revealed significantly higher expression of germ cell markers [PR domain
      containing 1, with ZNF domain (PRDM1, BLIMP1), developmental pluripotency
      associated 3 (DPPA3, STELLA), deleted in azoospermia-like (DAZL), and VASA
      (DDX4)] in GFP-positive cells than in GFP-negative cells. Moreover, the GFP
      positive cells from POI-iPSCs had reduced expression of the family with sequence
      similarity 122C (FAM122C), inhibitor of kappa light polypeptide gene enhancer in
      B-cells, kinase gamma (IKBKG), and RNA binding motif protein, X-linked (RBMX),
      genes located in the deleted region of the X chromosome and that are highly
      expressed in differentiated germ cells, compared with cells from normal iPSCs.
      LIMITATIONS, REASONS FOR CAUTION: Gene expression profiling indicated that the
      germ cells differentiated from POI-iPSCs were pre-meiotic. Therefore, how the
      differentiated primordial germ cells could progress further to meiosis and form
      follicles remains to be determined in the study of POI. WIDER IMPLICATIONS OF THE
      FINDINGS: Our results might provide an in vitro model for studying germ cell
      development in patients with POI. STUDY FUNDING/COMPETING INTERESTS: This work
      was supported by grants from the Major State Basic Research Development Program
      of China (No. 2012CB944901), the National Science Foundation of China (No.
      81222007 and 81471432), the Program for New Century Excellent Talents in
      University and the Fundamental Research Funds for Central Universities (No.
      721500003). The authors have no competing interests to declare. TRIAL
      REGISTRATION NUMBER: Not applicable.

PMID- 25586788
TI  - EZH2 expression is a prognostic factor in childhood intracranial ependymoma: a
      Canadian Pediatric Brain Tumor Consortium study.
AB  - BACKGROUND: The cure rate for childhood intracranial ependymoma is approximately
      70% in the setting of a gross total resection followed by radiation, but
      management remains challenging in patients with residual disease. Therefore,
      robust biomarkers are needed to guide the development of new targeted therapy.
      The authors evaluated the expression of several biomarkers in pediatric
      intracranial ependymoma and observed that the expression of enhancer of zeste
      homolog 2 (EZH2), a polycomb complex protein involved in epigenetic regulation of
      gene expression, was independently associated with poor survival. METHODS: Tissue
      microarray immunostaining was performed on 180 ependymoma samples from 12 of 16
      Canadian pediatric centers. Expression levels of EZH2, Ki-67, B lymphoma Moloney
      murine leukemia virus insertion region 1 homolog, tumor protein 16 (P16), Y-box
      binding protein 1, phosphorylated protein kinase B (pAKT), and epidermal growth
      factor receptor were evaluated. Cox regression analyses were performed, and the
      Kaplan-Meier method was used to construct survival curves. RESULTS: EZH2
      expressed in 16% of tumors was associated with inferior 5-year overall survival.
      Ki-67 and pAKT levels were associated with a poor outcome in patients with
      posterior fossa ependymoma, and the absence of P16 was associated with a poor
      outcome in patients with supratentorial ependymoma. Multivariate analysis
      revealed that younger age and EZH2 expression (95% confidence interval, 1.1-36.0)
      were independent markers of a poor prognosis. CONCLUSIONS: EZH2 is a novel,
      independent marker of a poor prognosis in patients with ependymoma, especially in
      those who have tumors located in the posterior fossa. EZH2, pAKT, and P16 are
      potential therapeutic targets, particularly for patients who have tumors in which
      standard gross total resection plus fractionated radiotherapy is not feasible.

PMID- 25586789
TI  - Potential cell-specific functions of CXCR4 in atherosclerosis.
AB  - The chemokine CXCL12 and its receptor CXCR4 form an important axis contributing
      to cellular functions in homeostasis and disease. In addition, the atypical
      CXCL12 receptor CXCR7 may shape the availability and function of CXCL12. Further
      to their role through progenitor cell mobilization, CXCL12 and CXCR4 may affect
      native atherogenesis by modifying atherosclerosis-relevant cellular functions.
      This short review intends to provide a concise summary of current knowledge with
      regards to cell-specific functions of CXCL12 and its receptors CXCR4 and CXCR7
      with potential implications for the initiation and progression of
      atherosclerosis. 

PMID- 25586790
TI  - Minimum inhibitory concentrations of equine Corynebacterium pseudotuberculosis
      isolates (1996-2012).
AB  - BACKGROUND: Few studies report the minimum inhibitory concentrations for
      antimicrobials against equine Corynebacterium pseudotuberculosis isolates.
      HYPOTHESIS/OBJECTIVES: To evaluate trends in the in vitro activities of 20
      antimicrobials against equine Corynebacterium pseudotuberculosis isolates from
      1996 to 2012 and to determine if a relationship exists between the minimum
      inhibitory concentration (MIC) and location of the abscess. ANIMALS:
      Corynebacterium pseudotuberculosis isolates from 196 horses with naturally
      occurring disease. METHODS: Retrospective and cross-sectional design. Medical
      records were reviewed to obtain clinical and MIC data. Minimum inhibitory
      concentrations were determined by the microdilution technique. The MIC results
      over 3 periods were compared (1996-2001, 2002-2006, 2007-2012). RESULTS: The
      MIC90 values for clinically relevant antimicrobials were as follows:
      chloramphenicol <= 4 MUg/mL, enrofloxacin <= 0.25 MUg/mL, gentamicin <= 1 MUg/mL,
      penicillin =0.25 MUg/mL, rifampin <= 1 MUg/mL, tetracycline <= 2 MUg/mL,
      trimethoprim-sulfamethoxazole (TMS) <= 0.5 MUg/mL, ceftiofur =2 MUg/mL, and
      doxycycline <= 2 MUg/mL. There were no significant changes in MIC results over
      the study period. There was no relationship between MIC patterns and abscess
      location. CONCLUSIONS AND CLINICAL IMPORTANCE: The MIC50 and MIC90 values of
      antimicrobials evaluated in this study for equine isolates of C.
      pseudotuberculosis did not vary over time. Abscess location was not associated
      with different MIC patterns in cultured isolates. Several commonly used
      antimicrobials are active in vitro against C. pseudotuberculosis in vitro.

PMID- 25586791
TI  - Transmission of infection to liver transplant recipients from donors with
      infective endocarditis: lessons learned.
AB  - Donors not meeting standard criteria, such as those with bacteremia, are now
      being used in response to the increasing need for organs for transplantation.
      Recommended strategies to prevent the occurrence of donor-derived bacteremia
      include the use of directed antibiotic prophylaxis. However, this approach does
      not eliminate the risk of infection transmission. Similarly, the management of
      organ recipients from donors with infective endocarditis (IE) remains
      uncharacterized. We report 2 cases of donor-derived bacterial infections in liver
      transplant recipients despite pathogen-specific antibiotic prophylaxis. In both
      instances, the donors had documented IE treated with appropriate antimicrobial
      therapy and clearance of bacteremia. Recipients had very distinctive clinical
      outcomes likely related to pathogen virulence and the extent of donor infection.
      Persistent infection in the transplanted liver should be suspected in organ
      recipients of a liver from donors with IE, despite the absence of bacteremia at
      the time of death and organ procurement. For eradication, recipients may require
      prolonged pathogen-directed antimicrobial therapy, such as is used for
      endovascular infections. Prompt recognition of donors with IE, appropriate
      notification, and prolonged antibiotic prophylaxis are key to reducing the risk
      of such donor-derived infections. 

PMID- 25586793
TI  - Interprofessional collaboration in mental health crisis response systems: a
      scoping review.
AB  - Post deinstitutionalization saw the rise of mental health crisis (MHC) response
      in Canada. First points of contact for individuals in a MHC are often police
      services or emergency departments. Professionals in these areas may report
      feeling unprepared, ill equipped, and a lack of confidence to work with clients
      in crisis. Police indicate that this work is time consuming, demanding, and "not
      their job". Entry points can exacerbate the crisis given the chaotic, over
      stimulating and frightening environment of emergency departments and the
      perceived threat of police officers. Despite the outcry of support for working
      more collaboratively, little is known about the impact Interprofessional
      collaboration (IPC) has in mental health crisis response systems (MHCRS).
      PURPOSE: Given this challenge, the aim of this scoping review is to contribute to
      understanding the current state of knowledge related to IPC in MHCRS. METHODS: A
      scoping reviews was conducted to address the research topic. RESULTS: Review of
      the literature identified 18 articles for inclusion, 5 experimental or
      exploratory papers, 7 models of care, and 6 discussion papers. Analysis
      identified the following themes: Support for interprofessional collaboration,
      quest for improved care delivery system, merging distinct visions of care, and
      challenges to interprofessional collaboration. Implications for practice, policy,
      and research are discussed, as well as issues in the literature related to: Lack
      of conceptual clarity, absent client perspectives, unequal representation across
      sectors, and a young and emergent body of literature. CONCLUSION: Key concepts
      need better conceptualization, and further empirical research is needed.
      IMPLICATIONS FOR REHABILITATION: Conceptualizing mental health crisis (MHC)
      response as occurring within a system of services, rather than independent
      sectors, is critical to meeting the needs of clients. Purposefully built in
      mechanisms to sustain collaboration across care teams and services are required.
      Merging the distinct, and at times conflicting, visions of care espoused by the
      diverse sectors involved in MHC response requires deliberate effort.

PMID- 25586792
TI  - Amino acid composition analysis of secondary transport proteins from Escherichia
      coli with relation to functional classification, ligand specificity and
      structure.
AB  - We have performed an amino acid composition (AAC) analysis of the complete
      sequences for 235 secondary transport proteins from Escherichia coli, which have
      functions in the uptake and export of organic and inorganic metabolites, efflux
      of drugs and in controlling membrane potential. This revealed the trends in
      content for specific amino acid types and for combinations of amino acids with
      similar physicochemical properties. In certain proteins or groups of proteins,
      the so-called spikes of high content for a specific amino acid type or
      combination of amino acids were identified and confirmed statistically, which in
      some cases could be directly related to function and ligand specificity. This was
      prevalent in proteins with a function of multidrug or metal ion efflux. Any tool
      that can help in identifying bacterial multidrug efflux proteins is important for
      a better understanding of this mechanism of antibiotic resistance. Phylogenetic
      analysis based on sequence alignments and comparison of sequences at the N- and C
      terminal ends confirmed transporter Family classification. Locations of specific
      amino acid types in some of the proteins that have crystal structures (EmrE,
      LacY, AcrB) were also considered to help link amino acid content with protein
      function. Though there are limitations, this work has demonstrated that a basic
      analysis of AAC is a useful tool to use in combination with other computational
      and experimental methods for classifying and investigating function and ligand
      specificity in a large group of transport or other membrane proteins, including
      those that are molecular targets for development of new drugs. 

PMID- 25586794
TI  - Effectiveness of commercial video gaming on fine motor control in chronic stroke
      within community-level rehabilitation.
AB  - PURPOSE: The purpose of this study was to investigate the effectiveness of
      commercial gaming as an intervention for fine motor recovery in chronic stroke.
      METHODS: Ten chronic phase post-stroke participants (mean time since CVA = 39
      mos; mean age = 72 yrs) completed a 16-session program using the Nintendo Wii for
      15 min two times per week with their more affected hand (10 right handed).
      Functional recovery (Jebsen Hand Function Test (JHFT), Box and Block Test (BBT),
      Nine Hole Peg Test (NHPT)), and quality of life (QOL; Stroke Impact Scale (SIS))
      were measured at baseline (pre-testing), after 8 sessions (mid-testing) and after
      16 sessions (post-testing). RESULTS: Significant improvements were found with the
      JHFT, BBT and NHPT from pre-testing to post-testing (p = 0.03, p = 0.03, p =
      0.01, respectively). As well, there was an increase in perceived QOL from pre
      testing to post-testing, as determined by the SIS (p = 0.009). CONCLUSION:
      Commercial gaming may be a viable resource for those with chronic stroke. Future
      research should examine the feasibility of this as a rehabilitation tool for this
      population. IMPLICATIONS FOR REHABILITATION: Stroke survivors often live with
      lasting effects from their injury, however, those with chronic stroke generally
      receive little to no rehabilitation due to a perceived motor recovery plateau.
      Virtual reality in the form of commercial gaming is a novel and motivating way
      for clients to complete rehabilitation. The Nintendo Wii may be a feasible device
      to improve both functional ability and perceived quality of life in chronic
      stroke survivors.

PMID- 25586795
TI  - Reliability and validity of the Falls Efficacy Scale-International after hip
      fracture in patients aged >= 65 years.
AB  - PURPOSE: To assess the measurement properties of the Falls Efficacy Scale
      International (FES-I) in patients after a hip fracture aged >= 65 years. METHODS:
      In a sample of 100 patients, we examined the structural validity, internal
      consistency and construct validity. For the structural validity a confirmatory
      factor analysis was carried out. For construct validity predetermined hypotheses
      were tested. In a second sample of 21 older patients the inter-rater reliability
      was evaluated. RESULTS: The factor analysis yielded strong evidence that the FES
      I is uni-dimensional in patients with a hip fracture; the Cronbach's alpha was
      0.94. When testing the reliability, the intra-class correlation coefficient was
      0.72, while the Standard Error of Measurement was 6.4 and the Smallest Detectable
      Change was 17.7 (on a scale from 16 to 64). The Spearman correlation of the FES-I
      with the one-item fear of falling instrument was high (r = 0.68). The correlation
      was moderate with instruments measuring functional performance constructs and low
      with instruments measuring psychological constructs. CONCLUSIONS: Reliability and
      structural validity of the FES-I in patients after a hip fracture are good. The
      construct validity appears more closely related to functional performance
      constructs than to psychological constructs, suggesting that the concept measured
      by the FES-I may not capture all aspects of fear of falling. IMPLICATIONS FOR
      REHABILITATION: The Falls Efficacy Scale-International (FES-I), which is commonly
      used to measure fear of falling in community-dwelling older persons, can also be
      used to assess fear of falling in patients after a hip fracture. The reliability
      and the structural validity of the FES-I for these hip patients are good, whereas
      the construct validity of the FES-I is not optimal. The FES-I may not capture all
      aspects of fear of falling and may be more closely related to functional
      performance than to psychological concepts such as anxiety.

PMID- 25586797
TI  - Involving family members in physiotherapy for older people transitioning from
      hospital to the community: a qualitative analysis.
AB  - PURPOSE: To generate an understanding of the opinions of key people associated
      with a program for older people transitioning from hospital back to the community
      and explore their thoughts around training family members to help provide
      physiotherapy. METHOD: A qualitative study using focus groups and semi-structured
      interviews was conducted. Participants included patients admitted to a
      transitional care program, their family members, physiotherapists working in
      transitional care and members of a consumer group from the health service where
      the transitional care program was based. Data were transcribed verbatim and a
      thematic analysis was conducted. RESULTS: Four patients, four family members,
      four consumer group members and eight physiotherapists participated in this
      study. Three themes emerged: family members providing physiotherapy may improve
      outcomes for patients; training family members to provide physiotherapy should
      include key elements and be individualised; and involving family members in
      physiotherapy may impact positively and negatively on people and relationships.
      CONCLUSIONS: Older people transitioning from hospital to the community are at
      risk of functional decline and may receive very little physiotherapy. Training
      family members to assist with physiotherapy was perceived as a way to improve
      patient outcomes and relationships between patients and their family, although
      there were concerns raised about caregiver stress. Evaluation of the feasibility
      and effectiveness of this approach is warranted. IMPLICATIONS FOR REHABILITATION:
      Older people transitioning from hospital to the community are at risk of
      functional decline and often receive very little physiotherapy. Training family
      members to assist with simple physiotherapy programs may increase the amount of
      physiotherapy patients transitioning from hospital to the community can receive
      and improve functional outcomes for patients. Stakeholders perceive that
      individualising a program to patient and family member needs is important.
      Involving family members in physiotherapy may not increase caregiver stress and
      may improve relationship dynamics between patients and family members.

PMID- 25586798
TI  - Understanding factors that influence participation in physical activity among
      people with a neuromusculoskeletal condition: a review of qualitative studies.
AB  - PURPOSE: This review aims to describe the factors that influence participation in
      physical activity (PA) in people with neuromusculoskeletal (NMS) conditions.
      METHODS: A systematic search of six databases was conducted. Articles were
      included if the study qualitatively explored factors that influence participation
      in PA by individuals with a NMS condition. Fifteen peer-reviewed articles
      published between 2003 and 2013 were analysed for common themes and critically
      appraised. RESULTS: Results were categorised using the International
      Classification of Functioning, Disability and Health framework. The most common
      demotivators reported for the three areas of functioning, body function and
      structures, activities and participation were lack of walking balance, muscle
      weakness, pain, stiffness, bladder and blower problems, depression,
      thermoregulation and fear of injury. Fluctuating symptoms and fatigue were
      mentioned as demotivators in all of the progressive conditions. Maintaining
      independence, function and weight, and the prevention of secondary conditions
      were the leading motivators reported in this domain. Most common environmental
      barriers include accessibility, costs, transport and insufficient information and
      knowledge from health professionals. Social support is a consistent determinate
      of PA and is reported as a facilitator in every study. The most common personal
      demotivators include lack of motivation, feelings of self-consciousness and
      embarrassment in public, anxiety, frustration and anger. Personal motivators
      include goal setting and achieving, enjoyment, feeling good, feeling "normal",
      motivation and optimism, redefining self and escapism from everyday boundaries.
      CONCLUSIONS: Individuals with NMS conditions report complex common barriers,
      facilitators, demotivators and motivators to participation in PA. The way these
      factors influence participation in PA is unique to the individual; therefore, it
      is necessary to adopt an individually tailored approach when designing
      interventions. IMPLICATIONS FOR REHABILITATION: Individuals with
      neuromusculoskeletal conditions report common factors that influence
      participation in physical activity. It is the characteristics, attitude and
      beliefs of an individual that determine the way in which these factors influence
      participation in physical activity. Health professionals should be guided by the
      International Classification of Functioning, Disability and Health framework when
      assessing individuals, as the model will ensure all major factors of interest
      with regard to disability and physical activity behaviour are considered.
      Interventions to promote participation in physical activity in people with
      neuromusculoskeletal conditions require an individual approach that facilitates
      the assessment and management of an individual's barriers to physical activity. A
      multi-disciplinary approach may be required to address factors that influence
      participation in physical activity. Health professionals must be informed about
      other areas of expertise and draw on this when necessary.

PMID- 25586796
TI  - Activities and participation of children with cerebral palsy: parent
      perspectives.
AB  - PURPOSE: To explore parents' views of the activities and participation of
      children with cerebral palsy (CP) with a range of communicative abilities and the
      factors (personal and environmental) that influenced these. METHODS: Thirteen
      parents of children with CP aged 4-9 years participated in semi-structured
      individual interviews. Interviews were recorded, transcribed and analysed
      thematically. Identified codes and themes were mapped to the domains of the
      International Classification of Functioning, Disability and Health - Children and
      Youth Version (ICF-CY). RESULTS: Parents' responses reflected all ICF-CY domains
      comprising activity, participation and environmental factors. Codes were
      primarily mapped to the domains learning and applying knowledge, communication,
      mobility and interpersonal interactions and relationships. Key barriers
      identified included aspects of parents' own interactions with their child (e.g.
      not offering choices), unfamiliar people and settings, negative attitudes of
      others and children's frustration. Facilitators included support received from
      the child's family and school, being amongst children, having a familiar routine
      and the child's positive disposition. CONCLUSIONS: Despite the barriers
      experienced, children participated in a range of activities. Parents placed
      importance on communication and its influence on children's independence,
      behaviour and relationships. Barriers and facilitators identified highlight
      aspects of the environment that could be modified through intervention to enhance
      communication and participation. IMPLICATIONS FOR REHABILITATION: Children's
      activities and participation were largely related to early learning tasks (e.g.
      literacy), communication, mobility and interactions. Intervention aimed at
      improving activities and participation may address the various child, impairment,
      social and environment factors identified here as impacting on activities and
      participation (e.g. the child's personal characteristics, communication and
      physical impairments, the support and attitudes of others and the familiarity of
      the environment). Therapists will need to consider (and manage) the potential
      negative impact communication deficits may have on children's behaviour,
      independence and social skills which may in turn detrimentally impact on activity
      and participation.

PMID- 25586799
TI  - Ten years of hospitalisation for oral health-related conditions in Western
      Australia: an unjust dichotomy.
AB  - The objective of this study was: (1) to examine the demographics of in-patient
      oral health care by Aboriginal status; (2) to identify the mix of oral conditions
      by Aboriginal status; and (3) to describe trends over a 10-year period, comparing
      Aboriginal and non-Aboriginal groups. Hospitalisation data were obtained from the
      Western Australian Morbidity Data System (HMDS). The principal diagnosis, as
      classified by the International Classification of Disease (ICD-10AM), was
      obtained for every episode for adult patients who were discharged from all
      hospitals in Western Australia (WA) for the financial years 1999-2000 to 2008-09.
      Results indicated that more than 130000 persons were admitted to hospitals in WA
      over 10 years, for oral health-related conditions, at a direct cost of more than
      $400million. Most of those admitted were younger than 30 years, and 2.8% of all
      those admitted were Aboriginal people. Aboriginal people were admitted at
      significantly higher rates, for a very different mix of conditions, they were
      mostly from younger age groups, were mostly from very remote and the most
      disadvantaged areas and were almost all uninsured, compared with non-Aboriginal
      people. Hospital admissions for oral health-related conditions, as well as the
      mix of conditions that drive these hospitalisations, are strongly divided across
      social, racial and geographic variables, and remain a burden to the health-care
      system. 

PMID- 25586800
TI  - Validation of the SimSET simulation package for modeling the Siemens Biograph mCT
      PET scanner.
AB  - Monte Carlo simulation provides a valuable tool in performance assessment and
      optimization of system design parameters for PET scanners. SimSET is a popular
      Monte Carlo simulation toolkit that features fast simulation time, as well as
      variance reduction tools to further enhance computational efficiency. However,
      SimSET has lacked the ability to simulate block detectors until its most recent
      release. Our goal is to validate new features of SimSET by developing a
      simulation model of the Siemens Biograph mCT PET scanner and comparing the
      results to a simulation model developed in the GATE simulation suite and to
      experimental results. We used the NEMA NU-2 2007 scatter fraction, count rates,
      and spatial resolution protocols to validate the SimSET simulation model and its
      new features. The SimSET model overestimated the experimental results of the
      count rate tests by 11-23% and the spatial resolution test by 13-28%, which is
      comparable to previous validation studies of other PET scanners in the
      literature. The difference between the SimSET and GATE simulation was
      approximately 4-8% for the count rate test and approximately 3-11% for the
      spatial resolution test. In terms of computational time, SimSET performed
      simulations approximately 11 times faster than GATE simulations. The new block
      detector model in SimSET offers a fast and reasonably accurate simulation toolkit
      for PET imaging applications. 

PMID- 25586802
TI  - Pancreatitis in dogs and cats: definitions and pathophysiology.
AB  - Pancreatitis, or inflammation of the pancreas, is commonly seen in dogs and cats
      and presents a spectrum of disease severities from acute to chronic and mild to
      severe. It is usually sterile, but the causes and pathophysiology remain poorly
      understood. The acute end of the disease spectrum is associated with a high
      mortality but the potential for complete recovery of organ structure and function
      if the animal survives. At the other end of the spectrum, chronic pancreatitis in
      either species can cause refractory pain and reduce quality of life. It may also
      result in progressive exocrine and endocrine functional impairment. There is
      confusion in the veterinary literature about definitions of acute and chronic
      pancreatitis and there are very few studies on the pathophysiology of naturally
      occurring pancreatitis in dogs and cats. This article reviews histological and
      clinical definitions and current understanding of the pathophysiology and causes
      in small animals by comparison with the much more extensive literature in humans,
      and suggests many areas that need further study in dogs and cats. 

PMID- 25586803
TI  - Diagnosis of pancreatitis in dogs and cats.
AB  - Pancreatitis is the most common disorder of the exocrine pancreas in both dogs
      and cats. Ante-mortem diagnosis of canine and feline pancreatitis can be
      challenging. The clinical picture of dogs and cats with pancreatitis varies
      greatly (from very mild to severe or even fatal) and is characterised by non
      specific findings. Complete blood count, serum biochemistry profile and
      urinalysis should always be performed in dogs and cats suspected of having
      pancreatitis, although findings are not-specific for pancreatitis. Serum amylase
      and lipase activities and trypsin-like immunoreactivity (TLI) concentrations have
      no or only limited clinical value for the diagnosis of pancreatitis in either
      dogs or cats. Conversely, serum pancreatic lipase immunoreactivity (PLI)
      concentration is currently considered to be the clinicopathological test of
      choice for the diagnosis of canine and feline pancreatitis. Abdominal radiography
      is a useful diagnostic tool for the exclusion of other diseases that may cause
      similar clinical signs to those of pancreatitis. Abdominal ultrasonography can be
      very useful for the diagnosis of pancreatitis, but this depends largely on the
      clinician's experience. Histopathological examination of the pancreas is
      considered the gold standard for the diagnosis and classification of
      pancreatitis, but it is not without limitations. In clinical practice, a
      combination of careful evaluation of the animal's history, serum PLI
      concentration and abdominal ultrasonography, together with pancreatic cytology or
      histopathology when indicated or possible, is considered to be the most practical
      and reliable means for an accurate diagnosis or exclusion of pancreatitis
      compared with other diagnostic modalities. 

PMID- 25586801
TI  - Canine and feline pancreatitis: a challenging and enigmatic disease.

PMID- 25586804
TI  - Management of acute pancreatitis in dogs: a critical appraisal with focus on
      feeding and analgesia.
AB  - Knowledge about acute pancreatitis has increased recently in both the medical and
      veterinary fields. Despite this expansion of knowledge, there are very few
      studies on treatment interventions in naturally occurring disease in dogs. As a
      result, treatment recommendations are largely extrapolated from experimental
      rodent models or general critical care principles. General treatment principles
      involve replacing fluid losses, maintaining hydrostatic pressure, controlling
      nausea and providing pain relief. Specific interventions recently advocated in
      human medicine include the use of neurokinin-1 antagonists for analgesia and
      early interventional feeding. The premise for early feeding is to improve the
      health of the intestinal tract, as unhealthy enterocytes are thought to
      perpetuate systemic inflammation. The evidence for early interventional feeding
      is not supported by robust clinical trials to date, but in humans there is
      evidence that it reduces hospitalisation time and in dogs it is well tolerated.
      This article summarises the major areas of management of acute pancreatitis in
      dogs and examines the level of evidence for each recommendation. 

PMID- 25586805
TI  - Pancreatitis and triaditis in cats: causes and treatment.
AB  - Pancreatitis in cats is frequently accompanied by concurrent disease in other
      organ systems. Co-morbidities include hepatic lipidosis, inflammatory liver
      disease, bile duct obstruction, diabetes mellitus, inflammatory bowel disease,
      vitamin deficiency (B12/cobalamin, folate or K), intestinal lymphoma, nephritis,
      pulmonary thromboembolism and pleural and peritoneal effusions. "Triaditis" is
      the term used to describe concurrent inflammation of the pancreas, liver and
      small intestines. Triaditis has been reported in 50 to 56% of cats diagnosed with
      pancreatitis and 32 to 50% of those with cholangitis/inflammatory liver disease.
      A definitive diagnosis of triaditis is based on the histopathological evaluation
      of each organ. However, the specific conditions of each organ that constitute a
      diagnosis of triaditis remains to be defined. While the aetiopathogenesis of
      pancreatitis and its relationship to inflammation in other organ systems is
      unclear, preliminary studies point to a heterogeneous group of conditions with
      differential involvement of host inflammatory and immune responses and enteric
      bacteria. Comprehensive, prospective studies that simultaneously evaluate the
      presence of predefined clinical, clinicopathological and histopathological
      abnormalities, coupled with high-resolution evaluation of pancreaticobiliary
      morphology, immunological profiling and screening for bacterial colonisation are
      required to advance diagnosis and therapy. 

PMID- 25586807
TI  - A cross-sectional study of the quality of telephone triage in a primary care out
      of-hours service.
AB  - We evaluated the quality of telephone triage and the appropriateness of the
      decisions resulting from it at a primary care out-of-hours service. Four
      simulated clinical cases were used in the Incognito Standardized Patient method:
      an adult with nosebleed, an adult with fever, a child with fever and a child with
      vomiting. There was a set of obligatory questions for each case, translated from
      those used in a previous study. Quality was assessed by the proportion of
      questions asked by the call-handlers during telephone triage versus those that
      should have been asked. A total of 22 out-of-hours doctors were involved in the
      study, working in two different locations in the Verona city area. Over a 4-month
      period each of the four simulated clinical cases was used five times in calls to
      the two centres involved. The proportion of obligatory questions asked compared
      to those expected to be asked was 27-36%. On three occasions out of the 40
      simulations, all of which were considered to be manageable by telephone, the
      patient was advised to go to an outpatient clinic for a face-to-face evaluation.
      The average duration of the calls was 3 min 47 s. The quality of telephone triage
      in the regions studied was low and provided considerable room for improvement.
      This is relevant to patient safety and risk management of the service. 

PMID- 25586806
TI  - Diabetes mellitus and pancreatitis--cause or effect?
AB  - Diabetes mellitus and pancreatitis are two distinct diseases encountered commonly
      in small animal practice. Whilst the clinical signs of diabetes mellitus are
      usually unmistakeable, a firm diagnosis of pancreatitis can prove more elusive,
      as clinical signs are often variable. Over the past 10 to 15 years, despite the
      fact that the clinical signs of diabetes mellitus are remarkably consistent, it
      has become more apparent that the underlying pathology of diabetes mellitus in
      dogs and cats is heterogeneous, with exocrine pancreatic inflammation
      accompanying diabetes mellitus in a number of cases. However, the question
      remains as to whether the diabetes mellitus causes the pancreatitis or whether,
      conversely, the pancreatitis leads to diabetes mellitus--as there is evidence to
      support both scenarios. The concurrence of diabetes mellitus and pancreatitis has
      clinical implications for case management as such cases may follow a more
      difficult clinical course, with their glycaemic control being "brittle" as a
      result of variation in the degree of pancreatic inflammation. Problems may also
      arise if abdominal pain or vomiting lead to anorexia. In addition, diabetic cases
      with pancreatitis are at risk of developing exocrine pancreatic insufficiency in
      the following months to years, which can complicate their management further.

PMID- 25586808
TI  - High mobile phone ownership, but low Internet and email usage among pregnant, HIV
      infected women attending antenatal care in Johannesburg.
AB  - We investigated mobile phone usage amongst HIV-positive pregnant women attending
      antenatal services in a primary care clinic in Johannesburg (n = 50). We
      conducted a semi-structured interview and asked them about their mobile phone,
      Internet and email use. The median age of the women was 28 years, 36% had moved
      one or more times in the past year, and most were employed or recently employed,
      albeit earning low wages. Nearly all women (94%) reported that they did not share
      their phone and 76% of the SIM cards were registered to the woman herself. The
      median time with the current phone was one year (range 1 month-6 years) and the
      median time with the current phone number was three years (range 1 month-13
      years). Even though 42% of the participants were from outside South Africa, they
      all had mobile phone numbers local to South Africa. About one-third of
      respondents reported Internet use (30%) and about one-fifth reported using email
      (18%). Overall, 20% accessed the Internet and 10% accessed email on their mobile
      phone. Mobile phone interventions are feasible amongst HIV-positive pregnant
      women and may be useful in prevention of mother-to-child transmission of HIV
      (PMTCT). Email and Internet-based interventions may not yet be appropriate. 

PMID- 25586809
TI  - A pilot study of a mobile phone application to improve lifestyle and adherence of
      patients with kidney disease.

PMID- 25586810
TI  - Telemonitoring for chronic obstructive pulmonary disease: a cost and cost-utility
      analysis of a randomised controlled trial.
AB  - We compared the costs and cost-effectiveness of telemonitoring vs usual care for
      patients with chronic obstructive pulmonary disease (COPD). A total of 256
      patients were randomised to either telemonitoring or usual care. In the
      telemonitoring arm, the touch-screen telemonitoring equipment transmitted data to
      clinical teams monitoring the patients. Total healthcare costs were estimated
      over a 12-month period from a National Health Service perspective and quality
      adjusted life year (QALYs) were estimated by the EQ-5D tool. Telemonitoring was
      not significantly more costly than usual care (mean difference per patient
      L2065.90 (P < 0.18). The increased costs were predominantly due to telemonitoring
      service costs and non-significantly higher secondary care costs. Telemonitoring
      for COPD was not cost-effective at a base case of L137,277 per QALY with only 15%
      probability of being cost-effective at the usual threshold of L30,000 per QALY.
      Although there was some statistical and methodological uncertainty in the
      measures used, telemonitoring was not cost-effective in the sensitivity analyses
      performed. It seems unlikely that a telemonitoring service of the kind that was
      trialled would be cost-effective in providing care for people with COPD. 

PMID- 25586811
TI  - Client satisfaction with telehealth services in home health care agencies.
AB  - We assessed client satisfaction with the home telemonitoring service provided by
      14 home health care agencies in five US states. Clients were randomised to two
      groups. Telehealth services (health monitoring and patient safety) were provided
      to 450 experimental subjects. Control subjects (n = 409) received usual care.
      Clients were asked to rate their satisfaction with their service providers on 25
      items, at baseline, 6 months post-discharge (to home) and 12 months post
      discharge. The mean age of the clients was 78 years. Out of the initial 859
      subjects, 490 had dropped out of the study by the 12-month follow-up, an overall
      attrition rate of 57%. There were similar proportions of clients reporting high
      satisfaction with external systems at baseline and at 6 months; at 12 months,
      there were significantly more clients in the experimental group who reported high
      satisfaction (P = 0.049). There were similar proportions of clients reporting
      high satisfaction with internal systems at baseline and at 12 months; at 6
      months, there were significantly more clients in the experimental group who
      reported high satisfaction (P = 0.031). Clients with home monitoring were more
      satisfied with health-related and medical services post-discharge than those
      receiving usual care over a 6-12 month period. 

PMID- 25586812
TI  - A randomised clinical trial of the effectiveness of home-based health care with
      telemonitoring in patients with COPD.
AB  - We studied the effect of telemonitoring in addition to usual care compared to
      usual care alone in patients with chronic obstructive pulmonary disease (COPD). A
      total of 110 patients with moderate to severe COPD were recruited from a
      specialist respiratory service in Northern Ireland. Patients had at least two of:
      emergency department admissions, hospital admissions or emergency general
      practitioner (GP) contacts in the 12 months before the study. Exclusion criteria
      were patients who had any respiratory disorder other than COPD, or were
      cognitively unable to learn the process of monitoring. Patients were randomised
      to receive six months of home telemonitoring with usual care, or six months of
      usual care. The primary outcome measure was disease-specific quality of life, as
      measured by the St George's Respiratory Questionnaire for COPD patients (SGRQ-C).
      Of 100 patients completing the study, 48 patients were randomised to
      telemonitoring and 52 patients were randomised to the control group. The SGRQ-C
      scores improved significantly in the intervention group compared to usual care (P
      = 0.001). The HADS anxiety score was significantly higher in the telehealth group
      compared to the usual care group (P = 0.01). There were significantly more
      contacts with the Community Respiratory Team in the telemonitoring group compared
      to the control group (P = 0.029). There were no significant between group
      differences in EQ-5D scores, HADS depression scores, GP activity, emergency
      department visits, hospital admissions or exacerbations. The total cost to the
      health service of the intervention over the 6-month study period was L2039,
      giving an estimated ICER of L203,900. In selected patients with COPD,
      telemonitoring was effective in improving health-related quality of life and
      anxiety, but was not a cost-effective intervention. 

PMID- 25586813
TI  - The effect of telemedicine on the duration of treatment in dementia patients.
AB  - We studied 442 patients who met the DSM-IV-TR criteria for dementia and whose
      treatment was initiated at the Kangwon National University Hospital (KNUH) in
      Chuncheon. Over a five-year period, there were 259 patients who regularly visited
      the KNUH dementia clinic in person, and 168 patients who received medical
      services from the dementia clinic via telemedicine. The telemedicine patients
      attended a public health centre in Hongcheon, a facility located in a rural area
      about 50 km south east of the KNUH. The mean treatment duration was significantly
      longer for the telemedicine group than for the clinical visit group (P < 0.001),
      with durations of 26.6 and 14.6 months, respectively. Low Clinical Dementia
      Rating scores (hazard ratio = 1.47, 95% confidence interval = 1.26-1.71) and use
      of telemedicine (hazard ratio = 0.55, 95% confidence interval = 0.42-0.72) were
      found to be independent predictive factors of increased treatment duration. These
      findings suggest that telemedicine may be useful in slowing disease progression
      in dementia patients in rural areas. 

PMID- 25586814
TI  - Feasibility and accuracy of using mobile phone images of electrocardiograms to
      initiate the cardiac catheterization process.
AB  - We assessed the feasibility of interpreting the presence of ST-segment elevation
      myocardial infarction (STEMI) using ECGs captured and transmitted by mobile
      phones. Transmitted ECGs were interpreted by four independent and blinded
      physicians, who classified them as STEMI, non-STEMI or indeterminate. After 2-4
      weeks the same physicians were given the original paper ECGs for interpretation.
      In total, 87 ECGs were randomly selected for review. The overall agreement
      between the digital image readings and the printed copy readings was 94%. Of the
      87 patients, 65 (75%) had cardiac catheterization following a STEMI ECG and 22
      (25%) did not receive cardiac catheterization. The accuracy of digital ECGs and
      printed ECGs when compared to the findings from cardiac catheterization was
      similar. Agreement in ECG interpretations between printed images and mobile phone
      images was excellent, and both had similar accuracy in activating the cardiac
      catheterization laboratory. Mobile phone transmission is an inexpensive method of
      evaluating ECG images sent from pre-hospital settings to the emergency
      department. 

PMID- 25586815
TI  - Can clans protect adolescent players of massively multiplayer online games from
      violent behaviors?
AB  - OBJECTIVES: To examine whether clan membership mediates observed associations
      between violent game content and externalizing behaviors among youth who play
      massively multiplayer online games (MMOGs). METHODS: Responses from 486 11- to 18
      year-olds who: live in the United States, read English, have been online at least
      once in the past 6 months, and have played MMOGs in the past year were examined.
      Generalized estimating equations were used to estimate the population-averaged
      incident rate ratio of aggressive, delinquent, and seriously violent behaviors
      among MMOG players given one's self-reported exposure to in-game content
      depicting violence. RESULTS: Twenty-nine percent of all youth respondents played
      MMOGs in the past year. Rates of aggressive, IRR: 1.59, 95% CI [1.11, 2.26], and
      delinquent, IRR: 1.44, 95% CI [0.99, 2.08], behaviors were significantly higher
      for MMOG players who were in clans versus not in clans. For females, clan
      membership attenuated but did not eliminate the observed relation between
      exposure to in-game violent content and both aggressive and seriously violent
      behavior (16% and 10% reductions in IRR, respectively); whereas for males, clan
      membership was largely uninfluential (i.e., less than 2% change). CONCLUSIONS:
      Clan membership is neither associated with lower rates of externalizing behaviors
      for youth, nor does it affect the likelihood of reporting externalizing behaviors
      among male players. There is some suggestion that clan membership may attenuate
      the concurrent association between in-game violent content and some externalizing
      behaviors for females.

PMID- 25586817
TI  - Bond cleavage, fragment modification and reassembly in enantioselective three
      component reactions.
AB  - Chemical bond cleavage and reconstruction are common processes in traditional
      rearrangement reactions. In contrast, the process that involves bond cleavage,
      fragment modification and then reconstruction of the modified fragment provides
      an efficient way to build structurally diversified molecules. Here, we report a
      palladium(II)/chiral phosphoric acid catalysed three-component reaction of
      aryldiazoacetates, enamines and imines to afford alpha-amino-delta-oxo pentanoic
      acid derivatives in good yields with excellent diastereoselectivities and high
      enantioselectivities. The stereoselective reaction went through a unique process
      that involves cleavage of a C-N bond, modification of the resulting amino
      fragment and selective reassembly of the modified fragment. This innovative multi
      component process represents a highly efficient way to build structurally
      diversified polyfunctional molecules in an atom and step economic fashion. A keto
      iminium is proposed as a key intermediate and a chiral palladium/phosphate
      complex is proposed as an active catalyst. 

PMID- 25586816
TI  - Media use and depression: exposure, household rules, and symptoms among young
      adolescents in the USA.
AB  - OBJECTIVES: To determine the longitudinal and cross-sectional associations
      between different types of electronic media use (mobile phones, TV, computers,
      video games, and music) and young adolescents' depressive symptoms, and to
      explore the potential for household media rules to reduce young people's
      depression. METHODS: 126 young adolescents were recruited from the Northeastern
      USA. Each type of media use was assessed using survey questions, time use
      diaries, and ecological momentary assessment. The Beck Depression Index for
      Primary Care was administered at baseline and 1 year later as part of a
      questionnaire that also included items assessing the presence of household rules
      about TV and video games. RESULTS: Baseline use of mobile phones and TV viewing
      were associated with higher levels of depression 1 year later controlling for
      demographic information and baseline depression score. Having household rules
      about TV at baseline predicted lower levels of depression at follow-up.
      CONCLUSIONS: Both TV viewing and mobile phone use may contribute to the
      development of depressive symptoms. Implementing household rules about the
      duration and content of TV could help reduce depression in young adolescents.

PMID- 25586818
TI  - Exercise-associated hyponatremic encephalopathy and exertional heatstroke in a
      soldier: High rates of fluid intake during exercise caused rather than prevented
      a fatal outcome.
AB  - Athletes are often advised to drink in order to "fully replace bodyweight losses"
      in order to prevent exertional heatstroke (EHS) during exercise in the heat.
      There is little evidence that "dehydration" in the range experienced by athletes
      adversely affects thermoregulation or is the exclusive cause of EHS. In contrast
      it is established that excess fluid intake can cause exercise-associated
      hyponatremia (EAH) sometimes associated with encephalopathy (EAHE). As part of a
      series of experiments to determine optimal fluid replacement during exercise in
      the heat, we studied a group of exceptionally well-conditioned and heat-adapted
      members of the South African National Defence Force. A 20 year old male started a
      time restricted 50 km route-march in a dry bulb temperature that reached 37.5
      degrees C (WBGT of 33.6 degrees C, relative humidity of 85%). Pre-march plasma
      osmolality, serum [Na(+)] and total body water measures indicated euhydration.
      Fluid was available ad libitum and isotonic sports drinks at 5 km intervals.
      Fluid intake and core body temperature (Tc) were recorded throughout while he was
      tracked by a global positioning system measuring distance travelled, position and
      speed. Comparing the total fluid intake of the soldier (12930 mL) to the rest of
      the participants (mean intake of 9 038 mL) up to 40 km, it is evident that his
      intake was 3892 mL (approximately 300 mL h(-1)) more than the mean for group. At
      approximately 17h14 the soldier was found lying by himself at the side of the
      route, 2.24 km from the finish point. He passed away the next day in a medical
      care facility. This tragic event provides the valuable opportunity to present
      data on the pacing, temperature regulation and fluid consumption of an
      exceptional athlete during the development of a fatal case of combined EAHE and
      EHS. Pacing, fluid intake, Tc and environmental condition data are presented for
      5 km intervals throughout the march. We propose a novel hypothesis on the
      possible contribution of EAHE to the development of EHS.

PMID- 25586819
TI  - Continued effects of context reinstatement in recognition.
AB  - The context reinstatement effect refers to the enhanced memory performance found
      when the context information paired with a target item at study is re-presented
      at test. Here we investigated the consequences of the way that context
      information is processed in such a setting that gives rise to its beneficial
      effect on item recognition memory. Specifically, we assessed whether reinstating
      context in a recognition test facilitates subsequent memory for this context,
      beyond the facilitation conferred by presentation of the same context with a
      different study item. Reinstating the study context at test led to better
      accuracy in two-alternative forced choice recognition for target faces than did
      re-pairing those faces with another context encountered during the study phase.
      The advantage for reinstated over re-paired conditions occurred for both within
      subjects (Exp. 1) and between-subjects (Exp. 2) manipulations. Critically, in a
      subsequent recognition test for the contexts themselves, contexts that had
      previously served in the reinstated condition were recognized better than
      contexts that had previously served in the re-paired context condition. This
      constitutes the first demonstration of continuous effects of context
      reinstatement on memory for context. 

PMID- 25586821
TI  - Radiofrequency ablation of drug-resistant cancer cells using molecularly targeted
      carboxyl-functionalized biodegradable graphene.
AB  - Under ultralow radiofrequency (RF) power, transferrin-conjugated graphene
      nanoparticles can thermally ablate drug- or radiation-resistant cancer cells very
      effectively. The results suggest that graphene-based RF hyperthermia can be an
      efficient method to manage drug-/radiation-resistant cancers.

PMID- 25586822
TI  - Sustained ventricular tachycardia as the first manifestation of hydatid cyst
      located in the interventricular septum.
AB  - Echinococcus granulosus infection may manifest with cardiac involvement causing
      various symptoms. Here, we discuss a case of a young patient who presented with
      sustained ventricular tachycardia (VT) causing hemodynamic compromise. Diagnosis
      of cardiac hydatid cyst was established with echocardiography, computed
      tomography imaging, and serological examination. After surgical removal of the
      cyst VT did not recur. 

PMID- 25586823
TI  - Shoulder surgery.

PMID- 25586824
TI  - Erratum to: Prediction of osteonecrosis collapse of the femoral head based on the
      proportion of the proximal sclerotic rim.

PMID- 25586826
TI  - Monitoring the Effect of Metal Ions on the Mobility of Artemia salina Nauplii.
AB  - This study aims to measure the effect of toxic aqueous solutions of metals on the
      mobility of Artemia salina nauplii by using digital image processing. The
      instrument consists of a camera with a macro lens, a dark chamber, a light source
      and a laptop computer. Four nauplii were inserted into a macro cuvette, which
      contained copper, cadmium, iron and zinc ions at various concentrations. The
      nauplii were then filmed inside the dark chamber for two minutes and the video
      sequence was processed by a motion tracking algorithm that estimated their
      mobility. The results obtained by this system were compared to the mortality
      assay of the Artemia salina nauplii. Despite the small number of tested
      organisms, this system demonstrates great sensitivity in quantifying the mobility
      of the nauplii, which leads to significantly lower EC50 values than those of the
      mortality assay. Furthermore, concentrations of parts per trillion of toxic
      compounds could be detected for some of the metals. The main novelty of this
      instrument relies in the sub-pixel accuracy of the tracking algorithm that
      enables robust measurement of the deterioration of the mobility of Artemia salina
      even at very low concentrations of toxic metals. 

PMID- 25586825
TI  - The MAST(r) D68C test: an interesting tool for detecting extended-spectrum beta
      lactamase (ESBL)-producing Enterobacteriaceae.
AB  - The Mast(r) D68C test is a phenotypical test that allows the detection of
      extended-spectrum beta-lactamase (ESBL) production, even in AmpC-producing
      Enterobacteriaceae. We assessed its detection accuracy against a large collection
      of 106 Enterobacteriaceae isolates producing a wide diversity of well
      characterized beta-lactamases (53 ESBL producers, 25 Amp. producers, seven AmpC
      and ESBL producers, five carbapenemase producers, three carbapenemase and ESBL
      producers, one AmpC, carbapenemase, and ESBL producer, three TEM-1 producers,
      three SHV-1 producers, three OXA-1 producers, and one hyperOXY producer, ATCC
      35218, ATCC 25922 [a beta-lactamase-negative control strain]). The results were
      compared with those of the double disk test and the Clinical and Laboratory
      Standards Institute (CLSI) confirmatory test for the detection of ESBL. The
      sensitivity was 90.6 % for the synergy test, 87.5 % for the CLSI method, and only
      73.1 % for D68C, which, however, reached 92.1 % if the strains for which
      supplementary investigations were recommended and the complex mutant TEM (CMT)
      producing strains were excluded versus 94.1 % and 88.2 % for the other methods.
      The specificity was 90.2 % for the synergy test and 100 % for the CLSI method and
      D68C. D68C was also efficient in detecting AmpC-overproducing strains
      (sensitivity = 97 %, specificity = 95.9 %): among the 74 strains belonging to
      natural AmpC-producing species, the sensitivity and specificity were 100 and 94.8
      %, respectively. The Mast(r) D68C-test is a promising method that is easy to
      perform for the detection of current ESBLs and could also be useful for the
      detection of plasmid-encoded AmpC enzymes (sensitivity = 100 %). 

PMID- 25586827
TI  - Nonlinear impedance of whole cells near an electrode as a probe of mitochondrial
      activity.
AB  - By simultaneously measuring the bulk media and electrode interface voltages of a
      yeast (Saccharomyces cerevisiae) suspension subjected to an AC voltage, a yeast
      dependent nonlinear response was found only near the current injection
      electrodes. Computer simulation of yeast near a current injection electrode found
      an enhanced voltage drop across the yeast near the electrode due to slowed
      charging of the electrode interfacial capacitance. This voltage drop is
      sufficient to induce conformation change in membrane proteins. Disruption of the
      mitochondrial electron transport chain is found to significantly change the
      measured nonlinear current response, suggesting nonlinear impedance can be used
      as a non-invasive probe of cellular metabolic activity. 

PMID- 25586828
TI  - Kinetic ELISA in microfluidic channels.
AB  - In this article, we describe the kinetic ELISA of Blue Tongue and Epizootic
      Hemorrhagic Disease viral antibodies in microfluidic channels by monitoring the
      rate of generation of the enzyme reaction product under static conditions. It has
      been shown that this format of the immunoassay allows very reliable quantitation
      of the target species using inexpensive glass microchips and a standard
      epifluorescence microscope system coupled to a CCD camera. For the viral
      antibodies assayed here, the limit of detection (LOD) for the analyte
      concentration in our microchips was established to be 3-5 times lower than that
      obtained on commercial microwell plates using a fiftieth of the sample volume and
      less than a third of the incubation time. Our analyses further show that when
      compared to the end-point ELISA format, the kinetic mode of this assay yields an
      improvement in the LOD by over an order of magnitude in microfluidic devices.
      This benefit is primarily realized as the observed variation in the background
      fluorescence (signal at the start of the enzyme reaction period) was
      significantly larger than that in the rate of signal generation upon repeating
      these assays in different microchannels/microchips. Because the kinetic ELISA
      results depend only on the latter quantity, the noise level in them was
      substantially lower compared to that in its end-point counterpart in which the
      absolute fluorescence measurements are of greater significance. While a similar
      benefit was also recorded through implementation of kinetic ELISAs on the
      microwell platform, the improvement in LOD registered in that system was not as
      significant as was observed in the case of microfluidic assays. 

PMID- 25586829
TI  - Hypothermic neuroprotection is associated with recovery of spectral edge
      frequency after asphyxia in preterm fetal sheep.
AB  - BACKGROUND AND PURPOSE: Electroencephalographic recovery is predictive of outcome
      after perinatal hypoxia-ischemia, but it is unknown whether early changes in
      electroencephalographic can predict the response to therapeutic hypothermia in
      the preterm brain. METHODS: 0.7 gestation fetal sheep received umbilical cord
      occlusion or sham occlusion for 25 minutes, followed by sham hypothermia or whole
      body cooling started either 30 minutes or 5 hours after occlusion and continued
      for 72 hours. RESULTS: Early but not delayed hypothermia reduced neuronal loss
      and microglial induction in the striatum, with faster recovery of spectral edge
      frequency, reduced seizure burden, and less suppression of
      electroencephalographic amplitude (P<0.05). CONCLUSIONS: Recovery of higher
      electroencephalographic frequencies may be a biomarker of effective hypothermic
      neuroprotection in the preterm-equivalent brain.

PMID- 25586831
TI  - Brief history of patent foramen ovale and stroke.

PMID- 25586832
TI  - Response to letter regarding article, "amplification of regulatory T cells using
      a CD28 superagonist reduces brain damage after ischemic stroke in mice".

PMID- 25586833
TI  - Influence of intracerebral hemorrhage location on incidence, characteristics, and
      outcome: population-based study.
AB  - BACKGROUND AND PURPOSE: The characteristics of intracerebral hemorrhage (ICH) may
      vary by ICH location because of differences in the distribution of underlying
      cerebral small vessel diseases. Therefore, we investigated the incidence,
      characteristics, and outcome of lobar and nonlobar ICH. METHODS: In a population
      based, prospective inception cohort study of ICH, we used multiple overlapping
      sources of case ascertainment and follow-up to identify and validate ICH
      diagnoses in 2010 to 2011 in an adult population of 695 335. RESULTS: There were
      128 participants with first-ever primary ICH. The overall incidence of lobar ICH
      was similar to nonlobar ICH (9.8 [95% confidence interval, 7.7-12.4] versus 8.6
      [95% confidence interval, 6.7-11.1] per 100 000 adults/y). At baseline, adults
      with lobar ICH were more likely to have preceding dementia (21% versus 5%;
      P=0.01), lower Glasgow Coma Scale scores (median, 13 versus 14; P=0.03), larger
      ICHs (median, 38 versus 11 mL; P<0.001), subarachnoid extension (57% versus 5%;
      P<0.001), and subdural extension (15% versus 3%; P=0.02) than those with nonlobar
      ICH. One-year case fatality was lower after lobar ICH than after nonlobar ICH
      (adjusted odds ratio for death at 1 year: lobar versus nonlobar ICH 0.21; 95%
      confidence interval, 0.07-0.63; P=0.006, after adjustment for known predictors of
      outcome). There were 4 recurrent ICHs, which occurred exclusively in survivors of
      lobar ICH (annual risk of recurrent ICH after lobar ICH, 11.8%; 95% confidence
      interval, 4.6%-28.5% versus 0% after nonlobar ICH; log-rank P=0.04). CONCLUSIONS:
      The baseline characteristics and outcome of lobar ICH differ from other
      locations.

PMID- 25586834
TI  - Letter by Gauberti and Vivien regarding article, "amplification of regulatory T
      cells using a CD28 superagonist reduces brain damage after ischemic stroke in
      mice".

PMID- 25586836
TI  - The Journal of Paediatrics and Child Health is celebrating its 50th anniversary.

PMID- 25586837
TI  - It is desirable that our neighbours have a clear image of all aspects of
      Australian life and culture.

PMID- 25586838
TI  - An explosion, a tsunami, a runaway train: half a century of genetics.
AB  - Let's face it. There is no way of writing about the last half century of genetics
      without getting a little bit excitable. All of the terms in the title of this
      piece have been used by otherwise level-headed geneticists to describe the pace
      of change in genetics over the past few years. The thing is--they are right.
      Genetics is moving faster and faster. Five years ago, few people would have
      predicted that we would be where we are today. Five years from now, presumably,
      it will seem like 2015 was some kind of Dark Age when nothing much was happening.
      So it would be easy to lose perspective on the achievements of the past, or to
      assume that nothing much was happening in genetics until recently. However,
      everything that is happening in genetics now rests on the foundations built up
      over the past century, and particularly the past half century. And through that
      time, this journal has been a part of that story.

PMID- 25586839
TI  - Fifty years of paediatric ethics.
AB  - In 1965, when the first issue of Journal of Paediatrics and Child Health
      appeared, medical ethics was just becoming established as a discipline. The sub
      speciality of paediatric ethics did not make an appearance until the late 1980s,
      with the first key texts appearing in the 1990s. Professional concern to practice
      ethically in paediatrics obviously goes much further back than that, even if not
      named as such. In clinical areas of paediatrics, the story of the last 50 years
      is essentially a story of progress - better understanding of disease, better
      diagnosis, more effective treatment, better outcomes. In paediatric ethics, the
      story of the last 50 years is a bit more complicated. In ethics, the idea of
      progress, rather than just change, is not so straightforward and is sometimes
      hotly contested. There has certainly been change, including some quite radical
      shifts in attitudes and practices, but on some issues, the ethical debate now
      looks remarkably similar to that of 40-50 years ago. This is the story of some
      things that have changed in paediatric ethics, some things that have stayed the
      same and the key ethical ideas lying beneath the surface. 

PMID- 25586835
TI  - Genes from a translational analysis support a multifactorial nature of white
      matter hyperintensities.
AB  - BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) of presumed vascular
      origin increase the risk of stroke and dementia. Despite strong WMH heritability,
      few gene associations have been identified. Relevant experimental models may be
      informative. METHODS: We tested the associations between genes that were
      differentially expressed in brains of young spontaneously hypertensive stroke
      prone rats and human WMH (using volume and visual score) in 621 subjects from the
      Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361
      subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology
      (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH
      associations found in subjects from CHARGE. RESULTS: Of 126 spontaneously
      hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume
      or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and
      MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10
      (XPNPEP1, P=6.7*10(-5); FARP1, P=0.024) plus another spontaneously hypertensive
      stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10
      respectively, were associated with WMH in subjects from CHARGE. Gene set
      enrichment showed significant associations for downregulated spontaneously
      hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936,
      we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM65 and
      TRIM47) and, for the first time, 1 (PMF1). CONCLUSIONS: Despite not passing
      multiple testing thresholds individually, these genes collectively are relevant
      to known WMH associations, proposed WMH mechanisms, or dementia: associations
      with Alzheimer's disease, late-life depression, ATP production, osmotic
      regulation, neurodevelopmental abnormalities, and cognitive impairment. If
      replicated further, they suggest a multifactorial nature for WMH and argue for
      more consideration of vascular contributions to dementia.

PMID- 25586840
TI  - Fifty years of immunisation in Australia (1964-2014): the increasing opportunity
      to prevent diseases.
AB  - Medicine has seen dramatic changes in the last 50 years, and vaccinology is no
      different. Australia has made a significant contribution to world knowledge on
      vaccine-preventable diseases. Certain deadly diseases have disappeared or become
      rare in Australia following successful introduction of vaccines. As diseases
      become rarer, public knowledge about the diseases and their serious consequences
      has decreased, and concerns about potential vaccine side effects have increased.
      To maintain confidence in immunisations, sharing of detailed information about
      the vaccines and the diseases we are trying to prevent is integral to the
      continued success of our public health programme. Modern quality immunisation
      programmes need to communicate complex information to immunisation providers and
      also to the general community. Improving immunisation coverage rates and
      eliminating the gap in coverage and timeliness between Aboriginal and Torres
      Strait Islander peoples and non-Indigenous people has become a high priority. 

PMID- 25586841
TI  - Historical aspects of rheumatic fever.
AB  - Few diseases have experienced such a remarkable change in their epidemiology over
      the past century, without the influence of a vaccine, than rheumatic fever.
      Rheumatic fever has all but disappeared from industrialised countries after being
      a frequent problem in the 1940s and 1950s. That the disease still occurs at high
      incidence in resource limited settings and in Indigenous populations in
      industrialised countries, particularly in Australia and New Zealand, is an
      indication of the profound effect of socio-economic factors on the disease.
      Although there have been major changes in the epidemiology of rheumatic fever,
      diagnosis remains reliant on careful clinical judgement and management is
      remarkably similar to that 50 years ago. Over the past decade, increasing
      attention has been given to rheumatic fever and rheumatic heart disease as public
      health issues, including in Australia and particularly in New Zealand, as well as
      in selected low and middle income countries. Perhaps the greatest hope for public
      health control of rheumatic fever is the development of a vaccine against
      Streptococcus pyogenes, and there are encouraging initiatives in this area.
      However, an effective vaccine is some time away and in the meantime public health
      efforts need to focus on effective translation of the known evidence around
      primary and secondary prophylaxis into policy and practice. 

PMID- 25586842
TI  - Paediatric cardiology: the last 50 years.
AB  - In the last half-century, the outlook for children with heart disease has changed
      dramatically. Morphologists have transformed our understanding of heart defects.
      Improved imaging methods, such as echocardiography, computed tomography and
      magnetic resonance imaging, have made diagnostic cardiac catheterisation almost
      redundant. However, interventional catheterisation has flourished as
      transcatheter procedures have replaced surgery for many lesions. The ability to
      pharmacologically manipulate the duct has revolutionised the management of the
      sick neonate with major heart disease. Better surgical techniques, such as deep
      hypothermia and circulatory arrest, allow repair of lesions in early infancy
      before irreversible complications develop. Advances in anaesthesia and intensive
      care have been integral. New sub-disciplines, such as fetal cardiology and
      electrophysiology, have emerged. The sum of these numerous developments is
      enormous. Lesions that were previously considered lethal are now routinely
      treated. Consequently, the great majority of children with major heart disease
      now reach adulthood in good health. 

PMID- 25586843
TI  - Conquering rotavirus: from discovery to global vaccine implementation.
AB  - Rotavirus, the commonest cause of severe dehydrating gastroenteritis world-wide,
      was discovered less than 50 years ago. It causes about 450,000 deaths per year in
      children <5 years of age and hospitalises millions more. Rotavirus vaccines have
      been shown to have a major impact on hospital admissions due to rotavirus
      gastroenteritis and all-cause gastroenteritis and reduce mortality in developing
      countries. In Australia, there has been a 71% decrease in rotavirus
      hospitalisations in children 0-5 years of age. From the discovery of rotavirus as
      the major causative agent for severe gastroenteritis, through vaccine development
      and vaccine post-marketing surveillance activities, Australian scientists and
      clinicians have played a significant role in the global effort to reduce the
      burden of rotavirus infection.

PMID- 25586844
TI  - In the beginning, there was general paediatrics ....
AB  - In this article, we address how general paediatrics has evolved and adapted to
      change over the past 50 years and speculate on its future directions. We compare
      the state of general paediatrics with that of general adult medicine. We argue
      that general paediatrics must continue to have a strong role both in paediatric
      teaching hospitals and the community. 

PMID- 25586845
TI  - Closing the gaps in child health in the Pacific: an achievable goal in the next
      20 years.
AB  - It is not inconceivable that by 2035 the substantial gaps in child health across
      the Pacific can close significantly. Currently, Australia and New Zealand have
      child mortality rates of 5 and 6 per 1000 live births, respectively, while
      Pacific island developing nations have under 5 mortality rates ranging from 13 to
      16 (Vanuatu, Fiji and Tonga) to 47 and 58 per 1000 live births (Kiribati and
      Papua New Guinea, respectively). However, these Pacific child mortality rates are
      falling, by an average of 1.4% per year since 1990, and more rapidly (1.9% per
      year) since 2000. Based on progress elsewhere, there is a need to (i) define the
      specific things needed to close the gaps in child health; (ii) be far more
      ambitious and hopeful than ever before; and (iii) form a new regional compact
      based on solidarity and interdependence. 

PMID- 25586846
TI  - Regression in autism spectrum disorders.
AB  - Since the Journal of Paediatrics and Child Health was first published, there has
      been substantial change in the field of autism spectrum disorders (ASDs) with an
      exponential increase in the amount of funded and published research. In this
      paper, we focus on regression in children with ASD, a phenomenon that remains
      poorly understood. We discuss the implications of what we know about regression
      in ASD for the way we think about ASD more broadly and for paediatric practice.

PMID- 25586847
TI  - Attention-deficit/hyperactivity disorder: the past 50 years.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental
      disorder and one of the main diagnoses seen by general paediatricians today.
      Despite the impression often portrayed in the media, it is not a new condition;
      in fact it has been described for over 200 years. The past 50 years has seen a
      progressive increase in our understanding of the underlying neurocognitive
      deficits in ADHD, and over the past 20 years behavioural genetics and
      neuroimaging studies have shed light on the complex causal factors and
      neurobiological processes operating. The plethora of ADHD research has advanced
      our knowledge of the condition, but so far has had little impact on improving
      clinical practice. Stimulant medication has been the mainstay of symptomatic
      treatment for over 30 years; however, it is still unclear how developmental
      trajectories can be modified to achieve best outcomes. It is hoped that novel
      therapies and more individualised management will evolve over the coming decades.

PMID- 25586848
TI  - Lessons from 50 years of curing childhood leukaemia.
AB  - One of the great success stories of modern medicine is undoubtedly the remarkable
      improvement in outcome for childhood cancer, achieved through the work of the co
      operative groups enrolling patients in randomised controlled trials. In 1965,
      survival was almost zero; now 5-year survival rates exceed 80% in high-income
      countries. The lessons learned in the care of patients with the most common
      malignancy in childhood--acute lymphoblastic leukaemia--have been used in all
      other cancers of childhood and more recently in the management of adults. These
      lessons can be broadly applied in medical practice, because elements of
      laboratory science in all branches of pathology, as well as a deep understanding
      of biochemistry, physiology, pharmacology, genetics and molecular science, run
      through this story. Far from being a sad area of practice, paediatric haematology
      and oncology remains the champion of embedded clinical and translational
      research, diagnosis from bench to bedside and lifelong multidisciplinary
      management of the child and their family.

PMID- 25586849
TI  - Viewpoint article: Childhood obesity--looking back over 50 years to begin to look
      forward.
AB  - The last 50 years have seen the emergence of childhood obesity as a major public
      health concern and a condition now regularly encountered in routine general
      paediatric practice. Causes are extremely complex, bringing together
      multifactorial environmental factors and individual genetics, and we still do not
      have a clear understanding of why some children appear predisposed to exaggerated
      and sometimes extreme weight gain. Overweight and obese children of today face an
      uncertain future. They are likely to experience higher rates of type 2 diabetes
      and heart disease, as well as many other health problems. However, while the
      prevalence of childhood obesity has progressively increased over the last few
      decades, so has research into its underlying causes. This has led to large-scale
      trials aimed at improving prevention or treatment. As data have emerged from such
      studies, we have begun to accept that the heterogeneity of obesity means that
      broad 'common sense' strategies to address diet and activity will not lead to
      success on their own. Now is the time to begin to build on this information,
      dispelling myths and beliefs, in order to focus research efforts and take first
      steps towards more sophisticated strategies that go beyond the surface behaviours
      that simply potentiate obesity. Through carefully designed studies, aimed at
      tackling fundamental questions missed in the hasty development of 'common sense'
      approaches, will come answers that can lead to the development of more effective
      community- and health-care-orientated prevention and treatment programmes.

PMID- 25586850
TI  - Fifty years of allergy: 1965-2015.
AB  - The last 50 years in allergy could almost be considered the first 50 years. Over
      this time period, we have witnessed the emergence of allergy as a subspecialty,
      have seen and continue to observe a tremendous change in prevalence of allergic
      disease and have gained insight into the mechanisms that underlie allergic
      predisposition and disease manifestation. We have improved the care of children
      with many forms of allergic disease and now sit poised to be able to alter the
      natural history of allergic disease with the use of specific immunotherapy. There
      is much left to do in the next 50 years including understanding what underlies
      both the predisposition to atopic disease and its natural resolution and
      identifying the environmental cofactors involved in the 'allergic epidemic' and
      therefore targets for effective primary prevention. 

PMID- 25586851
TI  - Theatre of paediatric surgery.
AB  - In the 50 years since the first edition of this journal, operative paediatric
      surgery has undergone radical change. Many of the most common instruments are
      unchanged, both as a testament to their utility and in recognition of past
      surgeons remembered eponymously. Surrounding that basic core of instruments,
      theatre has changed radically as new tools and techniques have arisen. Surgeons
      have come down from their pedestals, recognising surgery as a team sport rather
      than a solo performance. More than half of the current paediatric surgical
      trainees are women, a higher proportion than in any other craft group of the
      Royal Australasian College of Surgeons. The appearance, and rapid development, of
      laparoscopy is to many observers the most notable change in surgery over the last
      50 years. Placed in its context though, it is simply the most prominent example
      of a frameshift in surgical thinking. The patient as a whole is now the focus,
      rather than just the disease. Recent developments are as much about minimising
      harm to normal tissues as they are about extirpating pathology. As a surgical
      maxim, 'Primum non nocere' is even more in evidence in 2015 than it was in 1965. 

PMID- 25586852
TI  - Fifty years of newborn screening.
AB  - Newborn screening has evolved fast following recent advances in diagnosis and
      treatment of disease, particularly the development of multiplex testing and
      applications of molecular testing. Formal evidence of benefit from newborn
      screening has been largely lacking, due to the rarity of individual disorders.
      There are wide international differences in the choice of disorders screened, and
      ethical issues in both screening and not screening are apparent. More evidence is
      needed about benefit and harm of screening for specific disorders and renewed
      discussion about the basic aims of newborn screening must be undertaken. 

PMID- 25586853
TI  - Sudden unexpected death in infancy: a historical perspective.
AB  - Epidemiological, developmental and pathological research over the last 40 years
      has done much to unravel the enigma of sudden unexpected death in infancy (SUDI)
      and sudden infant death syndrome (SIDS) that has afflicted the human condition
      for millennia. Modifications in infant care practices based on the avoidance of
      risk factors identified from a consistent epidemiological profile across time and
      multiple locations have resulted in dramatic reductions in the incidence of SUDI
      and SIDS in particular. The definition of SIDS (or unexplained SUDI) has been
      continually refined allowing enhanced multidisciplinary research, results of
      which can be more reliably compared between investigators. These latter expanded
      definitions mandating death scene investigations, evaluation of the circumstances
      of death and more comprehensive autopsies including additional ancillary testing
      have illuminated the importance of life-threatening sleep environments. The
      triple-risk hypothesis for SIDS has been increasingly validated and formulates an
      inextricable relationship between an infant's state of development, underlying
      pathological vulnerability and an unsafe sleep environment for sudden infant
      death to occur. Today, the major risk factors for SUDI are maternal smoking and
      bed sharing, and the challenge is to implement effective strategies that will
      reduce the exposure to such risks as was done with prone sleeping position. The
      challenges ahead include development of clinical methods and/or laboratory
      testing that will accurately identify which infants are at particularly high risk
      of SIDS but also means by which their deaths can be prevented. 

PMID- 25586854
TI  - Neurodevelopmental and behavioural paediatrics.
AB  - One of the notable shifts in Paediatrics across the last 50 years has been
      towards disorders that are chronic and qualitative in nature. In addition to
      physical health, these impact on childhood development, behaviour and wellbeing.
      Understanding and management of these problems extends the traditional biological
      toolkit of paediatrics into the complexities of uncertainties of psychological
      and social context. In Australasia, the profession has responded with the
      development of Community Paediatrics as a recognised sub-specialty, of which
      Neurodevelopmental and Behavioural Paediatrics is an important component. These
      developments are reviewed along with consideration of future challenges for this
      field of health care. 

PMID- 25586855
TI  - Serpiginous lesion on the foot.

PMID- 25586856
TI  - What is the diagnosis?

PMID- 25586859
TI  - Hitchhiker's guide to the literature: journal: Nature.

PMID- 25586860
TI  - The role of temperature in reported chickenpox cases from 2000 to 2011 in Japan.
AB  - Annual periodicities of reported chickenpox cases have been observed in several
      countries. Of these, Japan has reported a two-peaked, bimodal annual cycle of
      reported chickenpox cases. This study investigated the possible underlying
      association of the bimodal cycle observed in the surveillance data of reported
      chickenpox cases with the meteorological factors of temperature, relative
      humidity and rainfall. A time-series analysis consisting of the maximum entropy
      method spectral analysis and the least squares method was applied to the
      chickenpox data and meteorological data of 47 prefectures in Japan. In all of the
      power spectral densities for the 47 prefectures, the spectral lines were observed
      at the frequency positions corresponding to the 1-year and 6-month cycles. The
      optimum least squares fitting (LSF) curves calculated with the 1-year and 6-month
      cycles explained the underlying variation of the chickenpox data. The LSF curves
      reproduced the bimodal and unimodal cycles that were clearly observed in northern
      and southern Japan, respectively. The data suggest that the second peaks in the
      bimodal cycles in the reported chickenpox cases in Japan occurred at a
      temperature of approximately 8.5  degrees C. 

PMID- 25586862
TI  - Classification of solar cells according to mechanisms of charge separation and
      charge collection.
AB  - In the last decade, photovoltaics (PV) has experienced an important
      transformation. Traditional solar cells formed by compact semiconductor layers
      have been joined by new kinds of cells that are constituted by a complex mixture
      of organic, inorganic and solid or liquid electrolyte materials, and rely on
      charge separation at the nanoscale. Recently, metal organic halide perovskites
      have appeared in the photovoltaic landscape showing large conversion
      efficiencies, and they may share characteristics of the two former types. In this
      paper we provide a general description of the photovoltaic mechanisms of the
      single absorber solar cell types, combining all-inorganic, hybrid and organic
      cells into a single framework. The operation of the solar cell relies on a number
      of internal processes that exploit internal charge separation and overall charge
      collection minimizing recombination. There are two main effects to achieve the
      required efficiency, first to exploit kinetics at interfaces, favouring the
      required forward process, and second to take advantage of internal electrical
      fields caused by a built-in voltage and by the distribution of photogenerated
      charges. These principles represented by selective contacts, interfaces and the
      main energy diagram, form a solid base for the discussion of the operation of
      future types of solar cells. Additional effects based on ferroelectric
      polarization and ionic drift provide interesting prospects for investigating new
      PV effects mainly in the perovskite materials. 

PMID- 25586863
TI  - Templated fabrication of periodic arrays of metallic and silicon nanorings with
      complex nanostructures.
AB  - Here we report a scalable colloidal templating approach for fabricating periodic
      arrays of metallic and silicon nanorings with complex nanostructures. Non-close
      packed monolayer silica colloidal crystal prepared by a simple spin-coating
      technology is first used as template for making periodic arrays of mushroom-like
      composite nanostructures consisting of silica spherical caps and polymer stems.
      Subsequent metal sputtering and reactive ion etching lead to the formation of
      ordered asymmetric nickel nanorings which can be further utilized as etching
      masks for patterning periodic arrays of symmetric silicon nanorings. Moreover,
      periodic arrays of metallic and silicon concentric double nanorings can be
      fabricated by using the asymmetric nickel nanorings as templates. We have also
      demonstrated that gold concentric double nanorings show strong surface-enhanced
      Raman scattering (SERS) with a SERS enhancement factor of ~9.5 * 10(7) from
      adsorbed benzenethiol molecules. The SERS enhancement and the electric field
      amplitude distribution surrounding gold concentric double nanorings have been
      calculated by using finite element electromagnetic modeling. This new colloidal
      templating technique is compatible with standard microfabrication and enables
      wafer-scale production of a variety of periodic nanorings with hierarchical
      structures that could find important technological applications in plasmonic and
      magnetic devices. 

PMID- 25586861
TI  - Chirality-selected phase behaviour in ionic polypeptide complexes.
AB  - Polyelectrolyte complexes present new opportunities for self-assembled soft
      matter. Factors determining whether the phase of the complex is solid or liquid
      remain unclear. Ionic polypeptides enable examination of the effects of
      stereochemistry on complex formation. Here we demonstrate that chirality
      determines the state of polyelectrolyte complexes, formed from mixing dilute
      solutions of oppositely charged polypeptides, via a combination of electrostatic
      and hydrogen-bonding interactions. Fluid complexes occur when at least one of the
      polypeptides in the mixture is racemic, which disrupts backbone hydrogen-bonding
      networks. Pairs of purely chiral polypeptides, of any sense, form compact,
      fibrillar solids with a beta-sheet structure. Analogous behaviour occurs in
      micelles formed from polypeptide block copolymers with polyethylene oxide, where
      assembly into aggregates with either solid or fluid cores, and eventually into
      ordered phases at high concentrations, is possible. Chirality is an exploitable
      tool for manipulating material properties in polyelectrolyte complexation. 

PMID- 25586864
TI  - New contraceptive patch wearability assessed by investigators and participants in
      a randomized phase 3 study.
AB  - OBJECTIVE: To evaluate skin irritation and patch adhesiveness of a new weekly low
      dose levonorgestrel (LNG) and ethinyl estradiol (EE) contraceptive patch (LNG/EE
      patch). STUDY DESIGN: This analysis was part of an open-label, parallel-group,
      multicenter, phase 3 study that randomized healthy women to the LNG/EE patch (one
      patch weekly for three consecutive weeks, followed by a patch-free week for 13
      cycles) or to an oral contraceptive for six cycles followed by seven LNG/EE patch
      cycles. Participants selected patch application sites of abdomen, buttock or
      upper torso. Investigators rated patch adhesiveness and skin irritation using
      standardized scales. Participants rated skin irritation and itching daily using
      standardized scales and recorded patch fall-off on daily diary cards. RESULTS: A
      total of 32,508 patches were applied (n=1273). At the five clinic visits in which
      investigators rated the patches, they rated adhesiveness=0 (no lift) for >=84% of
      participants and skin irritation=absent/mild for 97% of patches. Participants
      reported that 2-3.7% of patches fell off and rated skin irritation as absent or
      mild for 92- 95% of patches, according to site. CONCLUSION: Investigator- and
      participant-rated assessments of LNG/EE patch adhesiveness and irritation
      demonstrated a low incidence of patch detachment, skin irritation and pruritus.
      IMPLICATIONS STATEMENT: This secondary analysis of a phase 3 clinical trial of a
      new weekly low-dose LNG and EE contraceptive patch, which used assessment by both
      investigators and participants, observed a low incidence of skin irritation,
      pruritus and patch detachment.

PMID- 25586866
TI  - Development of a novel multiplexed assay for quantification of transforming
      growth factor-beta (TGF-beta).
AB  - Changes in activity or levels of transforming growth factor-beta (TGF-beta) are
      associated with a variety of diseases; however, measurement of TGF-beta in
      biological fluids is highly variable. TGF-beta is biologically inert when
      associated with its latency-associated peptide (LAP). Most available immunoassays
      require exogenous activation by acid/heat to release TGF-beta from the latent
      complex. We developed a novel electrochemiluminescence-based multiplexed assay on
      the MesoScale Discovery(r) platform that eliminates artificial activation,
      simultaneously measures both active TGF-beta1 and LAP1 and includes an internal
      control for platelet-derived TGF-beta contamination in blood specimens. We
      optimized this assay to evaluate plasma levels as a function of activation type
      and clinical specimen preparation. We determined that breast cancer patients'
      plasma have higher levels of circulating latent TGF-beta (LTGF-beta) as measured
      by LAP1 than healthy volunteers (p < 0.0001). This assay provides a robust tool
      for correlative studies of LTGF-beta levels with disease, treatment outcomes and
      toxicity with a broad clinical applicability.

PMID- 25586867
TI  - Medicine of the thousand poems.

PMID- 25586865
TI  - Patient perspectives on online health information and communication with doctors:
      a qualitative study of patients 50 years old and over.
AB  - BACKGROUND: As health care systems around the world shift toward models that
      emphasize self-care management, there is increasing pressure for patients to
      obtain health information online. It is critical that patients are able to
      identify potential problems with using the Internet to diagnose and treat a
      health issue and that they feel comfortable communicating with their doctor about
      the health information they acquire from the Internet. OBJECTIVE: Our aim was to
      examine patient-identified (1) problems with using the Internet to identify and
      treat a health issue, (2) barriers to communication with a doctor about online
      health information seeking, and (3) facilitators of communication with a doctor
      about patient searches for health information on the Internet. METHODS: For this
      qualitative exploratory study, semistructured interviews were conducted with a
      sample of 56 adults age 50 years old and over. General concerns regarding use of
      the Internet to diagnose and treat a health issue were examined separately for
      participants based on whether they had ever discussed health information obtained
      through the Internet with a doctor. Discussions about barriers to and
      facilitators of communication about patient searches for health information on
      the Internet with a doctor were analyzed using thematic analysis. RESULTS: Six
      higher-level general concerns emerged: (1) limitations in own ability, (2)
      credibility/limitations of online information, (3) anxiety, (4) time consumption,
      (5) conflict, and (6) non-physical harm. The most prevalent concern raised by
      participants who communicated with a doctor about their online health information
      seeking related to the credibility or limitations in online information.
      Participants who had never communicated with a doctor about their online health
      information seeking most commonly reported concerns about non-physical harm. Four
      barriers to communication emerged: (1) concerns about embarrassment, (2) concerns
      that the doctor doesn't want to hear about it, (3) belief that there is no need
      to bring it up, and (4) forgetting to bring it up. Facilitators of communication
      included: (1) having a family member present at doctor visits, (2) doctor
      initiated inquiries, and (3) encountering an advertisement that suggested talking
      with a doctor. CONCLUSIONS: Overall, participants displayed awareness of
      potential problems related to online health information seeking. Findings from
      this study point to a set of barriers as well as facilitators of communication
      about online health information seeking between patients and doctors. This study
      highlights the need for enhanced patient communication skills, eHealth literacy
      assessments that are accompanied by targeted resources pointing individuals to
      high-quality credible online health information, and the need to remind patients
      of the importance of consulting a medical professional when they use online
      health resources to diagnose and treat a health issue.

PMID- 25586868
TI  - Unveiling SEER-CAHPS(r): a new data resource for quality of care research.
AB  - BACKGROUND: Since 1990, the National Cancer Institute (NCI) and Centers for
      Medicare and Medicaid Services (CMS) have collaborated to create linked data
      resources to improve our understanding of patterns of care, health care costs,
      and trends in utilization. However, existing data linkages have not included
      measures of patient experiences with care. OBJECTIVE: To describe a new resource
      for quality of care research based on a linkage between the Medicare Consumer
      Assessment of Healthcare Providers and Systems (CAHPS(r)) patient surveys and the
      NCI's Surveillance, Epidemiology and End Results (SEER) data. DESIGN: This is an
      observational study of CAHPS respondents and includes both fee-for-service and
      Medicare Advantage beneficiaries with and without cancer. The data linkage
      includes: CAHPS survey data collected between 1998 and 2010 to assess patient
      reports on multiple aspects of their care, such as access to needed and timely
      care, doctor communication, as well as patients' global ratings of their personal
      doctor, specialists, overall health care, and their health plan; SEER registry
      data (1973-2007) on cancer site, stage, treatment, death information, and patient
      demographics; and longitudinal Medicare claims data (2002-2011) for fee-for
      service beneficiaries on utilization and costs of care. PARTICIPANTS: In total,
      150,750 respondents were in the cancer cohort and 571,318 were in the non-cancer
      cohort. MAIN MEASURES: The data linkage includes SEER data on cancer site, stage,
      treatment, death information, and patient demographics, in addition to
      longitudinal data from Medicare claims and information on patient experiences
      from CAHPS surveys. KEY RESULTS: Sizable proportions of cases from common cancers
      (e.g., breast, colorectal, prostate) and short-term survival cancers (e.g.,
      pancreas) by time since diagnosis enable comparisons across the cancer care
      trajectory by MA vs. FFS coverage. CONCLUSIONS: SEER-CAHPS is a valuable resource
      for information about Medicare beneficiaries' experiences of care across
      different diagnoses and treatment modalities, and enables comparisons by type of
      insurance.

PMID- 25586870
TI  - "Targeted" consent for pragmatic clinical trials.
AB  - Research on interventions within the standard of care has enormous potential, yet
      it also raises several ethical and regulatory challenges. Perhaps the most
      important is determining what consent process is needed for these "pragmatic"
      clinical trials. Some argue that pragmatic clinical trials need to obtain in
      depth research consent. This approach ensures that patients are informed, but may
      introduce substantial selection bias and disruption of clinical care. Others
      argue that trials limited to interventions within the standard of care do not
      need to obtain research consent at all. While this approach avoids the problems
      with in-depth consent, it results in patients not knowing whether they are in
      research. The present manuscript proposes a way to avoid both sets of concerns.
      It argues that consent for research needs to supplement appropriate consent for
      standard care only to the extent that the research differs from standard care.
      Hence, pragmatic trials designed to mirror clinical care can obtain consent with
      only minimal additions to consent for standard care. This conclusion suggests
      that it may be possible for many pragmatic trials to obtain consent that is
      ethically appropriate, satisfies research regulations, and does not introduce
      substantial selection bias or clinical disruption. 

PMID- 25586869
TI  - Predicting Non-Adherence with Outpatient Colonoscopy Using a Novel Electronic
      Tool that Measures Prior Non-Adherence.
AB  - BACKGROUND: Accurately predicting the risk of no-show for a scheduled colonoscopy
      can help target interventions to improve compliance with colonoscopy, and thereby
      reduce the disease burden of colorectal cancer and enhance the utilization of
      resources within endoscopy units. OBJECTIVES: We aimed to utilize information
      available in an electronic medical record (EMR) and endoscopy scheduling system
      to create a predictive model for no-show risk, and to simultaneously evaluate the
      role for natural language processing (NLP) in developing such a model. DESIGN:
      This was a retrospective observational study using discovery and validation
      phases to design a colonoscopy non-adherence prediction model. An NLP-derived
      variable called the Non-Adherence Ratio ("NAR") was developed, validated, and
      included in the model. PARTICIPANTS: Patients scheduled for outpatient
      colonoscopy at an Academic Medical Center (AMC) that is part of a multi-hospital
      health system, 2009 to 2011, were included in the study. MAIN MEASURES: Odds
      ratios for non-adherence were calculated for all variables in the discovery
      cohort, and an Area Under the Receiver Operating Curve (AUC) was calculated for
      the final non-adherence prediction model. KEY RESULTS: The non-adherence model
      included six variables: 1) gender; 2) history of psychiatric illness, 3) NAR; 4)
      wait time in months; 5) number of prior missed endoscopies; and 6) education
      level. The model achieved discrimination in the validation cohort (AUC= =70.2 %).
      At a threshold non-adherence score of 0.46, the model's sensitivity and
      specificity were 33 % and 92 %, respectively. Removing the NAR from the model
      significantly reduced its predictive power (AUC = 64.3 %, difference = 5.9 %, p <
      0.001). CONCLUSIONS: A six-variable model using readily available clinical and
      demographic information demonstrated accuracy for predicting colonoscopy non
      adherence. The NAR, a novel variable developed using NLP technology,
      significantly strengthened this model's predictive power.

PMID- 25586871
TI  - Whole arm deletions of 18p: medical and developmental effects.
AB  - Deletions of the short arm of chromosome 18 have been well-described in case
      reports. However, the utility of these descriptions in clinical practice is
      limited by varied and imprecise breakpoints. As we work to establish genotype
      phenotype correlations for 18p-, it is critical to have accurate and complete
      clinical descriptions of individuals with differing breakpoints. In addition, the
      developmental profile of 18p- has not been well-delineated. We undertook a
      thorough review of the medical histories of 31 individuals with 18p- and a
      breakpoint in the centromeric region. We collected developmental data using
      mailed surveys and questionnaires. The most common findings included neonatal
      complications; cardiac anomalies; hypotonia; MRI abnormalities; endocrine
      dysfunction; strabismus; ptosis; and refractive errors. Less common features
      included holoprosencephaly and its microforms; hearing loss; and orthopedic
      anomalies. The developmental effects of the deletion appear to be less severe
      than reported in the literature, as average IQ scores were in the range of
      borderline intellectual functioning. Based on responses to standardized
      questionnaires, it appears this population has marked difficulty with activities
      of daily living, though several young adults were able to live independent of
      their parents. This manuscript represents the most comprehensive description of a
      cohort of 18p- individuals with identical breakpoints. Despite identical
      breakpoints, a great deal of phenotype variability remained among this
      population, suggesting that many of the genes on 18p- cause low-penetrance
      phenotypes when present in a hemizygous state. Future efforts will focus on the
      clinical description of individuals with more distal breakpoints and the
      identification of critical regions and candidate genes.

PMID- 25586872
TI  - Discreet and distinct clustering of five model membrane proteins revealed by
      single molecule localization microscopy.
AB  - Compartmentalization is a functionally important property of the plasma membrane,
      yet the underlying principles that organize membrane proteins into distinct
      domains are not well understood. Using single molecule localization microscopy,
      we assessed the clustering of five model membrane proteins in the plasma membrane
      of HeLa cells. All five proteins formed discrete and distinct nano-scaled
      clusters. The extent of clustering of the five proteins, independent of their
      membrane anchors, increased significantly when the fluorescent protein mEOS2 was
      employed, suggesting that protein-protein interactions are a key driver for
      clustering. Further, actin depolymerization or reduction of membrane order had a
      greater, and in some instances opposing effects on the clustering of membrane
      proteins fused to mEOS2 compared to PS-CFP2-fusion proteins. The data propose
      that protein interactions can override the lateral organization imposed by
      membrane anchors to provide an exquisite regulation of the mosaic-like
      compartmentalization of the plasma membrane. 

PMID- 25586873
TI  - Designing elastic organic crystals: highly flexible polyhalogenated N
      benzylideneanilines.
AB  - The intermolecular interactions and structural features in crystals of seven
      halogenated N-benzylideneanilines (Schiff bases), all of which exhibit remarkable
      flexibility, were examined to identify the common packing features that are the
      raison d'etre for the observed elasticity. The following two features, in part
      related, were identified as essential to obtain elastic organic crystals: 1) A
      multitude of weak and dispersive interactions, including halogen bonds, which may
      act as structural buffers for deformation through easy rupture and reformation
      during bending; and 2) corrugated packing patterns that would get interlocked
      and, in the process, prevent long-range sliding of molecular planes. 

PMID- 25586874
TI  - Ovulation requires the activation on proestrus of M1 muscarinic receptors in the
      left ovary.
AB  - We analyzed the effects of chemically blocking type 1 muscarinic receptors (M1R)
      on either the left or right ovary on ovulation rate, number of ova shed and
      steroid hormones levels. M1R were unilaterally blocked in ovary with the M1R
      selective antagonist pirenzepine (PZP). PZP was delivered into the bursa ovarica
      of the left or right ovary of adult rats at 13:00 h on proestrus day. PZP
      treatment in the left but not in the right ovary blocked ovulation. PZP did not
      modify the number of ova shed, nor progesterone or 17beta-estradiol serum levels.
      The surge of luteinizing hormone levels was diminished while that of follicle
      stimulating hormone did not change in animals treated with PZP in the left ovary.
      Interestingly, treatment with either synthetic luteinizing hormone-releasing
      hormone or human chorionic gonadotropin 1 h after PZP administration in the left
      ovary restored ovulation in both ovaries. The presence of M1R protein in the
      theca cells of the ovarian follicles as well as in cells of the corpus luteum was
      detected on proestrus day. These results suggest that M1R activation in the left
      ovary is required for pre-ovulatory gonadotropin-releasing hormone (GnRH)
      secretion and ovulation. Furthermore, these results also suggest that M1R in the
      left ovary might be regulating ovulation asymmetrically through a stimulatory
      neural signal relayed to the hypothalamus via the vagus nerve to induce the GnRH
      secretion which then triggers ovulation.

PMID- 25586876
TI  - Asymmetric interaction paired with a super-rational strategy might resolve the
      tragedy of the commons without requiring recognition or negotiation.
AB  - Avoiding the tragedy of the commons requires that one or more individuals in a
      group or partnership "volunteer", benefiting the group at a cost to themselves.
      Recognition and negotiation with social partners can maintain cooperation, but
      are often not possible. If recognition and negotiation are not always the
      mechanism by which cooperative partnerships avoid collective tragedies, what
      might explain the diverse social cooperation observed in nature? Assuming that
      individuals interact asymmetrically and that both "weak" and "strong" players
      employ a super-rational strategy, we find that tragedy of the commons can be
      avoided without requiring either recognition or negotiation. Whereas in the
      volunteer's dilemma game a rational "strong" player is less likely to volunteer
      to provide a common good in larger groups, we show that under a wide range of
      conditions a super-rational "strong" player is more likely to provide a common
      good. These results imply that the integration of super-rationality and
      asymmetric interaction might have the potential to resolve the tragedy of the
      commons. By illuminating the conditions under which players are likely to
      volunteer, we shed light on the patterns of volunteerism observed in variety of
      well-studied cooperative social systems, and explore how societies might avert
      social tragedies. 

PMID- 25586875
TI  - Subthreshold amplitude and phase resonance in models of quadratic type: nonlinear
      effects generated by the interplay of resonant and amplifying currents.
AB  - We investigate the biophysical and dynamic mechanisms of generation of
      subthreshold amplitude and phase resonance in response to sinusoidal input
      currents in two-dimensional models of quadratic type. These models feature a
      parabolic voltage nullcline and a linear nullcline for the recovery gating
      variable, capturing the interplay of the so-called resonant currents (e.g.,
      hyperpolarization-activated mixed-cation inward and slow potassium) and
      amplifying currents (e.g., persistent sodium) in biophysically realistic
      parameter regimes. These currents underlie the generation of resonance in medial
      entorhinal cortex layer II stellate cells and CA1 pyramidal cells. We show that
      quadratic models exhibit nonlinear amplifications of the voltage response to
      sinusoidal inputs in the resonant frequency band. These are expressed as an
      increase in the impedance profile as the input amplitude increases. They are
      stronger for values positive than negative to resting potential and are
      accompanied by a shift in the phase profile, a decrease in the resonant and phase
      resonant frequencies, and an increase in the sharpness of the voltage response.
      These effects are more prominent for smaller values of ? (larger levels of the
      time scale separation between the voltage and the resonant gating variable) and
      for values of the resting potential closer to threshold for spike generation. All
      other parameter fixed, as ? increases the voltage response becomes "more linear";
      i.e., the nonlinearities are present, but "ignored". In addition, the nonlinear
      effects are strongly modulated by the curvature of the parabolic voltage
      nullcline (partially reflecting the effects of the amplifying current) and the
      slope of the resonant current activation curve. Following the effects of changes
      in the biophysical conductances of realistic conductance-based models through the
      parameters of the quadratic model, we characterize the qualitatively different
      effects that resonant and amplifying currents have on the nonlinear properties of
      the voltage response. We identify different classes of resonant currents,
      represented by h- and slow potassium, according to whether they enhance (h-) or
      attenuate (slow potassium) the nonlinear effects. Finally, we use dynamical
      systems tools to investigate the dynamic mechanisms of generation of resonance
      and phase-resonance. We show that the nonlinear effects on the voltage response
      (e.g., amplification of the voltage response in the resonant frequency band and
      shifts in the resonant and phase-resonant frequencies) result from the ability of
      limit cycle trajectories to follow the unstable (right) branch of the voltage
      nullcline for a significant amount of time. This is a canard-related mechanism
      that has been shown to underlie the generation of intrinsic subthreshold
      oscillations in quadratic type models such as medial entorhinal cortex stellate
      cells. Overall, our results highlight the complexity of the voltage response to
      oscillatory inputs in nonlinear models and the roles that resonant and amplifying
      currents have in shaping these responses.

PMID- 25586877
TI  - Natural history of early first-trimester pregnancies implanted in Cesarean scars.
AB  - OBJECTIVE: To describe the ultrasound findings and natural history of pregnancies
      implanted within or on Cesarean section scars in the first trimester of
      pregnancy. METHODS: This was a prospective observational study of 10 women
      diagnosed with a pregnancy implanted in or on a Cesarean section scar in the
      first trimester, who declined medical intervention because of their desire to
      continue the pregnancy. The study population comprised women at < 12 weeks'
      gestation who were seen in our early pregnancy unit between January 2011 and
      September 2013. Nine women were followed up by serial ultrasound examinations and
      had detailed care plans for delivery at King's College Hospital (KCH). One woman
      was followed up and delivered at another teaching hospital. The first-trimester
      ultrasound findings were compared with the clinical outcome of the pregnancy.
      RESULTS: The nine patients who were followed up at KCH developed ultrasound
      findings of morbidly adherent placenta (MAP) in the second and third trimesters.
      All 10 patients were diagnosed with MAP at the time of delivery by Cesarean
      section. The gestational age at delivery ranged from 26 to 38 weeks. The uterus
      was conserved in five patients, and Cesarean hysterectomy was performed in the
      remaining five. All three women with complete implantation of the gestational sac
      within the scar and two of three cases with placental lakes in the first
      trimester had hysterectomies. The two cases with bulging of the gestational sac
      out of the uterine contour had a preterm emergency hysterectomy due to placenta
      percreta. Histology confirmed placenta accreta in the five hysterectomy
      specimens. There were no fetal or neonatal complications. CONCLUSIONS:
      Implantation of a pregnancy on or in a Cesarean section scar is a precursor of
      MAP; however, the degree of morbidity associated with this implantation is
      variable and difficult to predict based on first-trimester ultrasound findings
      only. The assessment of ongoing pregnancies implanted in Cesarean scars is most
      beneficial when performed between 7 and 9 weeks' gestation. Complete implantation
      within the myometrial defect, bulging of the trophoblast from the uterine contour
      and large placental lakes in the first trimester are ultrasound findings that may
      predict severe placenta accreta or percreta and consequently a poor outcome.

PMID- 25586879
TI  - Asymmetrically fused polyoxometalate-silver alkynide composite cluster.
AB  - We demonstrate that an asymmetric composite cluster,
      [Ag25{C=CC(CH3)3}16(CH3CN)4(P2W15Nb3O62)] (1), consisting of directly fused
      polyoxometalate and silver alkynide moieties can be facilely synthesized by a one
      pot reaction between a Nb-substituted Dawson-type polyoxometalate, H4[alpha
      P2W15Nb3O62](5-), and the mixture of (CH3)3CC=CAg and CF3SO3Ag. Single-crystal X
      ray diffraction revealed the structure of 1, where Ag atoms are selectively
      attached to the Nb-substituted hemisphere of the pedestal Dawson anion. Its
      structural integrity in the solution was demonstrated by (31)P NMR spectroscopy
      and analytical ultracentrifugation. The latter method also unveiled the stepwise
      formation mechanism of 1. 

PMID- 25586878
TI  - EBT Fidelity Trajectories Across Training Cohorts Using the Interagency
      Collaborative Team Strategy.
AB  - The Interdisciplinary Collaborative Team (ICT) strategy uses front-line providers
      as adaptation, training and quality control agents for multi-agency EBT
      implementation. This study tests whether an ICT transmits fidelity to subsequent
      provider cohorts. SafeCare was implemented by home visitors from multiple
      community-based agencies contracting with child welfare. Client-reported fidelity
      trajectories for 5,769 visits, 957 clients and 45 providers were compared using
      three-level growth models. Provider cohorts trained and live-coached by the ICT
      attained benchmark fidelity after 12 weeks, and this was sustained. Hispanic
      clients reported high cultural competency, supporting a cultural adaptation
      crafted by the ICT.

PMID- 25586880
TI  - A deadly cause of syncope.

PMID- 25586881
TI  - Bridging the gender gap in atrial fibrillation.
AB  - Women have a similar lifetime prevalence of non-valvular atrial fibrillation
      (NVAF) compared with that of men. Given the significant morbidity and potential
      mortality associated with NVAF, it is crucial to understand gender differences
      with NVAF. Women can be more symptomatic than men. Despite a higher baseline
      stroke risk, they are less likely to be on anticoagulation. Women have a greater
      risk of thromboembolism and a similar rate of bleeding risk compared with men on
      anticoagulation. Initial experience suggests that novel oral anticoagulants have
      similar safety and efficacy profile in men and women. Although women can have
      more adverse reactions from antiarrhythmic therapies, they are often referred
      later than men for ablation. As a group, a mitigating factor in ablation referral
      is that women also have a higher incidence of procedural complications from
      catheter ablation. This review summarizes the available literature highlighting
      significant gender-based differences and also highlights areas for research to
      improve NVAF outcomes in women. 

PMID- 25586883
TI  - Dereplication-guided isolation of depsides thielavins S-T and lecanorins D-F from
      the endophytic fungus Setophoma sp.
AB  - Dereplication methodology using UHPLC-DAD-QTOFMS was applied during the metabolic
      profiling investigation of the endophyte Setophoma sp., a fungus isolated from
      symptomless guava fruits. The approach performed allowed a fast analysis of the
      microbial secondary metabolites. From this fungus, seven highly C-alkylated
      depsides were isolated and identified as polyketides thielavins S, T, U and V and
      lecanorins D, E and F. Their structures were elucidated through spectroscopic
      methods including NMR, HRMS and especially with assistance of HRMS/MS
      experiments. The compounds were tested for quorum sensing regulation activity in
      the virulence gene expression of Staphylococcus aureus, but no inhibitory effect
      was detected. Nevertheless, moderate antibacterial activity was encountered in
      three of tested depsides, particularly with thielavin T, whose MIC was 6.25
      MUg/mL against S. aureus.

PMID- 25586882
TI  - Neuromelanin activates proinflammatory microglia through a caspase-8-dependent
      mechanism.
AB  - BACKGROUND: We have uncovered a caspase-dependent (caspase-8/caspase-3/7)
      signaling governing microglia activation and associated neurotoxicity.
      Importantly, a profuse non-nuclear activation of cleaved caspases 8 and 3 was
      found in reactive microglia in the ventral mesencephalon from subjects with
      Parkinson's disease, thus supporting the existence of endogenous factors
      activating microglia through a caspase-dependent mechanism. One obvious candidate
      is neuromelanin, which is an efficient proinflammogen in vivo and in vitro and
      has been shown to have a role in the pathogenesis of Parkinson's disease.
      Consequently, the goal of this study is to test whether synthetic neuromelanin
      activates microglia in a caspase-dependent manner. RESULTS: We found an in-vivo
      upregulation of CD16/32 (M1 marker) in Iba1-immunolabeled microglia in the
      ventral mesencephalon after neuromelanin injection. In vitro experiments using
      BV2 cells, a microglia-derived cell line, demonstrated that synthetic
      neuromelanin induced a significant chemotactic response to BV2 microglial cells,
      along with typical morphological features of microglia activation, increased
      oxidative stress and induction of pattern-recognition receptors including Toll
      like receptor 2, NOD2, and CD14. Analysis of IETDase (caspase-8) and DEVDase
      (caspase-3/7) activities in BV2 cells demonstrated a modest but significant
      increase of both activities in response to neuromelanin treatment, in the absence
      of cell death. CONCLUSIONS: Caspase-8 inhibition prevented typical features of
      microglia activation, including morphological changes, a high rate of oxidative
      stress and expression of key proinflammatory cytokines and iNOS.

PMID- 25586884
TI  - The small regulatory RNA FasX enhances group A Streptococcus virulence and
      inhibits pilus expression via serotype-specific targets.
AB  - Bacterial pathogens commonly show intra-species variation in virulence factor
      expression and often this correlates with pathogenic potential. The group A
      Streptococcus (GAS) produces a small regulatory RNA (sRNA), FasX, which regulates
      the expression of pili and the thrombolytic agent streptokinase. As GAS serotypes
      are polymorphic regarding (a) FasX abundance, (b) the fibronectin, collagen, T
      antigen (FCT) region of the genome, which contains the pilus genes (nine
      different FCT-types), and (c) the streptokinase-encoding gene (ska) sequence (two
      different alleles), we sought to test whether FasX regulates pilus and
      streptokinase expression in a serotype-specific manner. Parental, fasX mutant and
      complemented derivatives of serotype M1 (ska-2, FCT-2), M2 (ska-1, FCT-6), M6
      (ska-2, FCT-1) and M28 (ska-1, FCT-4) isolates were compared. While FasX reduced
      pilus expression in each serotype, the molecular basis differed, as FasX bound,
      and inhibited the translation of, different FCT-region mRNAs. FasX enhanced
      streptokinase expression in each serotype, although the degree of regulation
      varied. Finally, we established that the regulation afforded by FasX enhances GAS
      virulence, assessed by a model of bacteremia using human plasminogen-expressing
      mice. Our data are the first to identify and characterize serotype-specific
      regulation by an sRNA in GAS, and to show an sRNA directly contributes to GAS
      virulence. 

PMID- 25586886
TI  - Redox signaling and stress tolerance in plants: a focus on vitamin E.
AB  - Plants are subject to specific redox processes, in which photosynthesis plays a
      prominent role. Chloroplasts function in light at high oxygen tensions and are
      enormous generators of reactive oxygen species, mainly singlet oxygen. This side
      product of photosynthesis inflicts damage to thylakoid membranes at high
      concentrations, but at the same time it is an essential component of cellular
      signaling. Detoxification of singlet oxygen is achieved by different means,
      including quenching and scavenging by tocopherols, responsible for controlling
      singlet oxygen levels, and the extent of lipid peroxidation in chloroplasts.
      Here, environmental conditions leading to excess light in chloroplasts will be
      used to show the importance of singlet oxygen, tocopherols, and lipid
      peroxidation in cell signaling. Defects in antioxidant protection (e.g.,
      tocopherol deficiency) can lead to increased photo-oxidative damage, but also to
      the activation of defense pathways, illustrating the phenotypic plasticity
      evolved by plants to withstand stress. Most importantly, these studies show how
      redox signaling processes are integrated within the cell and illustrate the great
      capacity of plants to adapt to their environment.

PMID- 25586885
TI  - Barriers and facilitators of medication reconciliation processes for recently
      discharged patients from community pharmacists' perspectives.
AB  - BACKGROUND: Community pharmacists play a vital part in reconciling medications
      for patients transitioning from hospital to community care, yet their roles have
      not been fully examined in the extant literature. OBJECTIVES: The objectives of
      this study were to: 1) examine the barriers and facilitators community
      pharmacists face when reconciling medications for recently discharged patients;
      and 2) identify pharmacists' preferred content and modes of information transfer
      regarding updated medication information for recently discharged patients.
      METHODS: Community pharmacists were purposively and conveniently sampled from the
      Wisconsin (U.S. state) pharmacist-based research network, Pharmacy Practice
      Enhancement and Action Research Link (PEARL Rx). Community pharmacists were
      interviewed face-to-face, and transcriptions from audio recordings were analyzed
      using directed content analysis. The Theory of Planned Behavior (TPB) guided the
      development of questions for the semi-structured interviews. RESULTS: Interviewed
      community pharmacists (N = 10) described the medication reconciliation process to
      be difficult and time-consuming for recently discharged patients. In the context
      of the TPB, more barriers than facilitators of reconciling medications were
      revealed. Themes were categorized as organizational and individual-level themes.
      Major organizational-level factors affecting the medication reconciliation
      process included: pharmacy resources, discharge communication, and hospital
      resources. Major individual-level factors affecting the medication reconciliation
      process included: pharmacists' perceived responsibility, relationships, patient
      perception of pharmacist, and patient characteristics. Interviewed pharmacists
      consistently responded that several pieces of information items would be helpful
      when reconciling medications for recently discharged patients, including the
      hospital medication discharge list and stop-orders for discontinued medications.
      CONCLUSIONS: The TPB was useful for identifying barriers and facilitators of
      medication reconciliation for recently discharged patients from community
      pharmacists' perspectives. The elucidation of these specific facilitators and
      barriers suggest promising avenues for future research interventions to improve
      exchange of medication information between the community pharmacy, hospitals, and
      patients.

PMID- 25586887
TI  - The role of microRNAs in toxicology.
AB  - A number of environmental toxicants affect our health through physical,
      biological or chemical mechanisms. There is growing evidence indicating that
      microRNA (miRNA) plays an important role in toxicogenomics, disease aetiology and
      the effect of toxicants. This article summarises recent findings on miRNAs
      associated with various toxicants and those targeted in the development of
      therapeutics. Environmental epigenetic studies have revealed the role of miRNAs
      in the regulation of gene activities induced by environmental changes after
      exposure to toxic substances. Toxicant-induced changes in miRNA expression have a
      potential to be informative markers in the evaluation of toxicant risks. miRNAs
      are now considered to be predictive biomarkers or indicators of tissue injury due
      to toxicant exposure; thus, miRNAs can also be utilised as therapeutic targets. 

PMID- 25586888
TI  - Reply to the letter of Anderson J entitled "Comment on Schindler, BK; Weiss, T;
      Schutze, A; et al. Occupational exposure of air crews to tricresyl phosphate
      isomers and organophosphate flame retardants after fume events, Arch Toxicol
      (2013) 87:645-648".

PMID- 25586889
TI  - Novel image encryption based on quantum walks.
AB  - Quantum computation has achieved a tremendous success during the last decades. In
      this paper, we investigate the potential application of a famous quantum
      computation model, i.e., quantum walks (QW) in image encryption. It is found that
      QW can serve as an excellent key generator thanks to its inherent nonlinear
      chaotic dynamic behavior. Furthermore, we construct a novel QW-based image
      encryption algorithm. Simulations and performance comparisons show that the
      proposal is secure enough for image encryption and outperforms prior works. It
      also opens the door towards introducing quantum computation into image encryption
      and promotes the convergence between quantum computation and image processing. 

PMID- 25586890
TI  - Chemotherapy intensification in patients with advanced seminoma and adverse
      prognostic factors.
AB  - PURPOSE: The aim of our study was to identify factors which influence survival in
      patients with disseminated seminoma in the good prognostic group according to
      IGCCCG, as well as to evaluate the impact of treatment intensification in
      patients with negative prognostic factors. METHODS: We analyzed the database of
      the patients with metastatic seminoma who had received treatment at our
      department from 1986 to 2005. Inclusion criteria were as follows: morphologically
      verified seminoma; favorable prognosis according to IGCCCG; modern chemotherapy
      regimen (EP +/- bleomycin); AFP level <15 IU/ml; and HCG level <300 mIU/ml. The
      primary endpoint was overall survival (OS). RESULTS: With median follow-up 83
      months, 5-year OS rate was 91% in 206 patients. Only three negative prognostic
      factors were associated with OS: retroperitoneal lymph nodes >5 cm (p < 0.01),
      pulmonary metastases (p < 0.01) and LDH level >= 2.25 * ULN (p = 0.01). In view
      of the obtained data, we have changed our treatment approach since 2005. In case
      of any negative prognostic factors, we administered an intensified CT regimen-
      4BEP or 3BEP + 1EP. Prospective phase of the study included 34 patients with
      unfavorable prognosis. We observed an increase of 5-year OS rate in the
      intensified CT group in comparison with the standard CT group in patients with
      unfavorable prognostic from 85 to 100%. CONCLUSION: Administration of 4 cycles of
      induction CT (4BEP or 3BEP + 1EP) in patients with metastatic seminoma who have
      LDH level >= 2.25 ULN, and/or retroperitoneal lymph nodes >5 cm and/or pulmonary
      metastases results in decreased disease progression rate and significant gain in
      OS.

PMID- 25586891
TI  - Changes in fibrillin-1 expression, elastin expression and skin surface texture at
      sites of cultured epithelial autograft transplantation onto wounds from burn scar
      excision.
AB  - This study investigated the recovery process during which grafted cultured
      epithelium generated skin elasticity and skin surface microarchitecture. The
      subjects were 18 patients whose burn scars were excised at a depth not exposing
      the fat layer and who subsequently received cultured epithelial autografts. A
      total of 24 samples were obtained from the grafted sites: 6 samples within 6
      weeks (stage 1), 5 samples after 6 weeks and within 6 months (stage 2), 6 samples
      after 6 months and within 18 months (stage 3) and 7 samples beyond 18 months
      (stage 4) of transplantation. These samples were evaluated by taking replicas of
      skin surface, and histological changes of fibrillin-1 and elastin. The expression
      patterns were classified using a grading scale. The grade of skin surface texture
      was significantly higher at stage 3 and marginally significantly higher at stage
      4 compared with stage 1. The grade of fibrillin-1 was marginally significantly
      higher at stage 3 and significantly higher at stage 4 compared with stage 1. The
      grade of elastin was marginally significantly higher at stage 4 compared with
      stage 1. These results showed that it is important for patients to have skin care
      and avoid external forces for at least 18 months after transplantation. 

PMID- 25586892
TI  - Progestogen safety in multiple gestations: application of the Bradford Hill
      criteria.

PMID- 25586894
TI  - The pain--suffering association, a review.
AB  - OBJECTIVE: This review wished to determine the reported prevalence of suffering
      in various patient diagnostic groups and examine the evidence for the association
      of pain and suffering. DESIGN/SETTING: Twenty-four studies fulfilled inclusion
      exclusion criteria. They were divided into the following groups: advanced
      cancer/terminal illness/hospice patients (AC/TI/H) (7 studies); hastened
      death/assisted suicide/euthanasia patients (HD/AS/E) (14 studies); noncancer (NC)
      patients (3 studies). No chronic nonmalignant pain (CNMP) suffering studies
      fulfilled inclusion-exclusion criteria of this review. The reported prevalence of
      suffering for each study was abstracted and the overall percentage of sufferers
      in each grouping calculated. For those studies that provided a statistical
      relationship between pain and suffering information was abstracted for whether
      these studies supported/did not support the association of pain and suffering. A
      vote counting method was utilized to determine the overall percentage of studies
      supporting/not supporting this association. The consistency of this data for
      supporting this association was then rated by Agency for Health Care Research and
      Quality guidelines. RESULTS: The prevalence of suffering in each grouping was as
      follows: AC/IT/H 45.7%; HD/AS/E 81.9%; NC 19.2%; and all groupings combined
      59.9%. AC/TI/H and all groupings combined received an A rating (consistent
      evidence multiple studies for a statistical relationship between suffering and
      pain). HD/AS/E received a C (evidence which is inconsistent). For NC there were
      not enough studies for a consistency rating. CONCLUSIONS: The above results
      indicate a consistent association between suffering and pain in some patient
      groups. Studies addressing suffering are needed in CNPM patients.

PMID- 25586893
TI  - Efficacy of positive airway pressure on brain natriuretic peptide in patients
      with heart failure and sleep-disorder breathing: a meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVE: Positive airway pressure (PAP) has been recognized as an effective
      therapeutic option for sleep-disordered breathing (SDB) in patients with heart
      failure (HF), and it can improve left ventricular function. Whether PAP can
      ameliorate serum brain natriuretic peptide (BNP) levels, a biomarker of HF, is
      controversial. The purpose of the present study was to quantitatively assess the
      efficacy of PAP on BNP in patients with HF and SDB. METHODS: A systematic search
      of PubMed, Embase, Web of Science and Cochrane library identified six randomized
      controlled trials (RCTs), in which PAP was compared with medical therapy,
      subtherapeutic PAP or different types of PAP. The data of BNP were extracted and
      pooled into meta-analysis using STATA 12.0. RESULTS: Totally 6 RCT studies (7
      cohorts) with 222 patients were enrolled into analysis. The quality of each study
      was high and the heterogeneity (I(2) = 58.1%) was noted between studies. A
      significant reduction of BNP was observed after PAP treatment in patients with HF
      and SDB (SMD -0.517, 95% CI -0.764 to -0.270, z = 4.11, p = 0.000). CONCLUSION:
      Our meta-analysis of RCTs demonstrated that PAP elicits significant reduction of
      BNP in patients with HF and SDB.

PMID- 25586895
TI  - Association between the sense of coherence 13-item version scale score of
      pregnant women in the second trimester of pregnancy and threatened premature
      birth.
AB  - OBJECTIVES: The purpose of this study is to determine whether the score of the
      sense of coherence 13-item version (SOC-13) scale in the second trimester of
      pregnancy is associated with threatened premature birth. METHODS: All the
      subjects gave their informed written consent before their participation in the
      study. A self-reported questionnaire survey was conducted on the pregnant women
      at approximately 18 weeks of pregnancy. The questionnaire consisted of items on
      demographic characteristics, perinatal abnormalities, stress perception scale
      (SPS), and SOC-13 scale. Approximately 30 weeks of pregnancy after the first
      survey, we surveyed whether any treatment had been provided for threatened
      premature birth during the course of the current pregnancy. The study period was
      from December 2007 to February 2010. One hundred and seventy-seven pregnant women
      participated in the study, but only the data from 151 pregnant women were
      analyzed. RESULTS: Forty-three (28.5%) pregnant women had threatened premature
      birth and received some treatment. Logistic regression analysis was carried out
      with threatened premature birth as the dependent variable and age, childbirth
      history, smoking habit, history of miscarriage or premature birth in previous
      pregnancies, SPS score, and SOC-13 scale score as the independent variables. It
      was shown that SOC-13 scale score affected threatened premature birth (p < 0.001)
      and that a low SOC-13 scale score was associated with threatened premature birth.
      CONCLUSIONS: This study suggests that the SOC-13 scale score in the second
      trimester of pregnancy could be of great value in clinical health care of
      pregnant women with a risk of threatened premature birth in the subsequent course
      of pregnancy.

PMID- 25586896
TI  - Effect of short ageing on lees on the mannoprotein content, aromatic profile, and
      sensorial character of white wines.
AB  - In Albarino white wines, aging of wines on lees is a technique not used or only
      used empirically by some producers to obtain a distinctive character in the final
      wine. This study analyzes the influence of a short aging on lees on the chemical
      and sensorial parameters of this young white wine. Albarino grape must was
      inoculated with a locally selected yeast (Saccharomyces cerevisiae 1) and the
      effect of a short aging on lees was studied during different times (10, 20, 30,
      40, and 50 d). Mannoprotein content and the aromatic profile were determined and
      a sensorial analysis of the wines was conducted. Results showed that aging time
      was correlated with the concentration of some key aroma compounds and
      mannoproteins in Albarino wines. The best sensorial character was obtained in
      wines aged 20 d on lees. Further aging times decreased the sensorial quality of
      Albarino wine and modified its volatile profile and mannoprotein concentration. 

PMID- 25586897
TI  - Stories of the Accused: A Phenomenological Inquiry of MFTs and Accusations of
      Unprofessional Conduct.
AB  - Interviews were conducted with 10 MFTs (six females and four males) who had
      received a formal accusation of unprofessional conduct and went before state
      licensure boards in three different states. Accusations included dual
      relationships, financial fraud/errors, receiving DUIs, sexual misconduct, and
      emotionally harming a client. Utilizing Moustakas' (1994, Phenomenological
      research methods, Thousand Oaks, CA: Sage) transcendental phenomenology, five
      essential themes emerged: (a) The experience of being formally accused of
      unprofessional conduct is life-changing, (b) state MFT licensing boards are more
      punitive than rehabilitative, (c) obtaining support is vital, (d) making
      accusations creates stigma, (e) therapists were unprepared to handle accusations
      of unprofessional conduct. Clinical implications include the importance of
      supervision, personal therapy, and strategies for prevention and rehabilitation
      with this population. 

PMID- 25586898
TI  - Understanding the role of nitrogen in plasma-assisted surface modification of
      magnetic recording media with and without ultrathin carbon overcoats.
AB  - A novel scheme of pre-surface modification of media using mixed argon-nitrogen
      plasma is proposed to improve the protection performance of 1.5 nm carbon
      overcoats (COC) on media produced by a facile pulsed DC sputtering technique. We
      observe stable and lower friction, higher wear resistance, higher oxidation
      resistance, and lower surface polarity for the media sample modified in 70%Ar +
      30%N2 plasma and possessing 1.5 nm COC as compared to samples prepared using
      gaseous compositions of 100%Ar and 50%Ar + 50%N2 with 1.5 nm COC. Raman and X-ray
      photoelectron spectroscopy results suggest that the surface modification process
      does not affect the microstructure of the grown COC. Instead, the improved
      tribological, corrosion-resistant and oxidation-resistant characteristics after
      70%Ar + 30%N2 plasma-assisted modification can be attributed to, firstly, the
      enrichment in surface and interfacial bonding, leading to interfacial strength,
      and secondly, more effective removal of ambient oxygen from the media surface,
      leading to stronger adhesion of the COC with media, reduction of media corrosion
      and oxidation, and surface polarity. Moreover, the tribological, corrosion and
      surface properties of mixed Ar + N2 plasma treated media with 1.5 nm COCs are
      found to be comparable or better than ~2.7 nm thick conventional COC in
      commercial media.

PMID- 25586900
TI  - Factors associated with good adherence to self-care behaviours amongst
      adolescents with food allergy.
AB  - BACKGROUND: Our understanding of factors which affect adherence to health
      sustaining self-care behaviours in adolescents with food allergy is limited. This
      study used the Health Belief Model to explore the relationship between food
      allergic adolescents' health beliefs, demographic, structural and social
      psychological factors with adherence to self-care behaviours, including allergen
      avoidance and carrying emergency medication. METHODS: A cross-sectional study of
      188 13- to 19- olds identified from hospital prescribed auto-injectable
      epinephrine for food allergy. Data were collected on demographics, structural
      factors, social psychological factors, health beliefs and current adherence
      behaviour using a postal questionnaire. RESULTS: Full adherence was reported by
      16% of participants. Multivariate analysis indicated that adherence was more
      likely to be reported if the adolescents belonged to a support group (OR = 2.54,
      (1.04, 6.20) 95% CI), had an anaphylaxis management plan (OR = 3.22, (1.18, 8.81)
      95% CI), perceived their food allergy to be more severe (OR = 1.24, (1.01, 1.52)
      95% CI) and perceived fewer barriers to disease management (OR = 0.87, (0.79,
      0.96) 95% CI). CONCLUSIONS: Membership of a patient support group and having an
      anaphylaxis management plan were associated with good adherence to self-care
      behaviours in adolescents with food allergy. Our results suggest that
      interventions to improve provision and utilisation of management plans, address
      adolescents' perceptions of the severity of anaphylaxis and reduce barriers to
      disease management may facilitate good adherence behaviours than focussing on
      knowledge-based interventions.

PMID- 25586899
TI  - HIV viraemia during hepatitis B vaccination shortens the duration of protective
      antibody levels.
AB  - OBJECTIVES: Individuals with HIV infection often have early waning of protective
      antibody following hepatitis B virus (HBV) vaccination. HIV viraemia at the time
      of vaccination may limit the durability of serum anti-HBV surface antibody
      (HBsAb) levels. We investigated the relationship of HIV plasma viral load (VL)
      and duration of HBsAb among vaccinees enrolled in the US Military HIV Natural
      History Study. METHODS: We included in the study participants who had no history
      of prior HBV infection, who had received all HBV vaccine doses after HIV
      diagnosis, and who had demonstrated an initial vaccine response, defined as HBsAb
      >= 10 IU/L. Responders were retrospectively followed with serial HBV serology
      from the time of the last vaccine dose until the development of waning (HBsAb <
      10 IU/L) or the last HBsAb measurement. Time to and risk for waning were
      evaluated with Kaplan-Meier survival methods and Cox proportional hazards models,
      respectively. RESULTS: A total of 186 initial vaccine responders were identified.
      During 570 person-years of observation, HBsAb waned in 52 of 186 participants
      (28%). The cumulative proportion maintaining HBsAb >= 10 IU/L was 83% at 2 years
      and 56% at 5 years. Participants with an undetectable VL [hazard ratio (HR) 0.37;
      95% confidence interval (CI) 0.18-0.76] or with detectable VL of <= 10 000
      copies/mL (HR 0.46; 95% CI 0.21-1.00) had reduced risk of waning. Other factors
      including age, number of vaccine doses, CD4 count, and receipt of highly active
      antiretroviral therapy (HAART) were not significantly associated with risk of
      waning HBsAb. CONCLUSIONS: Undetectable or low HIV VL at the time of HBV
      vaccination is associated with greater durability of vaccine response in patients
      with HIV infection.

PMID- 25586901
TI  - Combination of ultrasound guided percutaneous microwave ablation and radioiodine
      therapy in benign thyroid diseases. A suitable method to reduce the 131I activity
      and hospitalization time?
AB  - AIM: Goiters and thyroid nodules are an ongoing problem in healthcare. There has
      not been any treatment of goiters and thyroid nodules based on the combined
      therapy of microwave ablation (MWA) and radioiodine therapy (RIT) until now. In
      this study the potential benefit of a combined therapy versus single RIT is
      evaluated in order to achieve improvements concerning 131I-dose and
      hospitalization time. PATIENTS, MATERIAL, METHODS: Ten patients with goiter and
      benign thyroid nodules or Graves' disease were included. Pre-ablation assessments
      included sonographical imaging, functional imaging with 99mTc and FNAB to collect
      data of nodules and total thyroid volume and to exclude malignancy. Prior to
      treatment, radioiodine uptake test was performed. MWA was operated under local
      anesthesia with a system working in a wavelength field 902-928 MHz. Post-MWA,
      thyroid volume was recalculated ultrasonically. Due to reduced vital volume,
      changes of 131I-dose and hospitalization time could be monitored. RESULTS: Mean
      absolute thyroid volume reduction by MWA before applying RIT was 22 +/- 11 ml,
      meaning a relative reduction of 24 +/- 6% (p < 0.05). Thereby, administered
      activity could be reduced by 393 +/- 188 MBq using the combined therapy,
      reflecting a relative reduction of 24 +/- 6% (p < 0.05). Additionally, mean
      hospitalization time was decreased by 2.1 +/- 0.8 days using MWA prior to RIT,
      implying a relative reduction of 28 +/- 6% (p < 0.05). CONCLUSION: Depending on
      ablated volume by MWA, RIT-monotherapy requires on average 31.2% more 131I
      activity than the combined therapy. The combined therapy remarkably decreases
      131I-dose and hospitalization time. The combined MWA and RIT therapy is a
      considerable, effective and safer alternative to surgery for the treatment of
      very large benign nodular goiters.

PMID- 25586902
TI  - Garlic and onions: their cancer prevention properties.
AB  - The Allium genus includes garlic, onions, shallots, leeks, and chives. These
      vegetables are popular in cuisines worldwide and are valued for their potential
      medicinal properties. Epidemiologic studies, while limited in their abilities to
      assess Allium consumption, indicate some associations of Allium vegetable
      consumption with decreased risk of cancer, particularly cancers of the
      gastrointestinal tract. Limited intervention studies have been conducted to
      support these associations. The majority of supportive evidence on Allium
      vegetables cancer-preventive effects comes from mechanistic studies. These
      studies highlight potential mechanisms of individual sulfur-containing compounds
      and of various preparations and extracts of these vegetables, including decreased
      bioactivation of carcinogens, antimicrobial activities, and redox modification.
      Allium vegetables and their components have effects at each stage of
      carcinogenesis and affect many biologic processes that modify cancer risk. This
      review discusses the cancer-preventive effects of Allium vegetables, particularly
      garlic and onions, and their bioactive sulfur compounds and highlights research
      gaps.

PMID- 25586905
TI  - Feasibility of lateral dose profile measurements in a small field using TLDs.
AB  - The purpose of this work was to study the feasibility of lateral dose profile
      measurements in a small field using thermoluminescent dosimeters (TLDs) and to
      evaluate the impact of the field size on the absorbed dose ratio factor fmd of
      LiF and Al2O3 TLDs. The Monte Carlo package BEAM/EGSNRC was used to simulate the
      lateral dose profile in solid water phantoms (RW3 slab phantom) with various
      field sizes beyond the build-up region for 6 MV x-rays, and a LiF : Mg, Cu, P (GR
      200) dosimeter with dimensions of 0.1  *  0.1  *  0.1 cm(3) was used to measure
      the lateral dose profile under the same conditions as the Monte Carlo
      simulations. To enable comparisons between dosimeters, Gafchromic EBT3 films were
      used. The results indicate that (1) the measured results are in agreement with
      the simulated results within the uncertainty of the simulation; (2) the values of
      fmd for Al2O3 and LiF in a 1  *  1 cm(2) field are 2.8% and 1.6% less,
      respectively, than those in a 10  *  10 cm(2) field; and (3) within the 80%
      profile region, the dose differences between TLDs and solid water are less than
      1%. In the 80-10% profile region, the TLD results are in agreement with the
      absorbed doses in the solid water within 1 mm. It is generally acceptable to
      ignore the impact of field size on the absorbed dose ratio factor fmd when the
      field sizes are larger than 1  *  1 cm(2) for LiF and 2  *  2 cm(2) for Al2O3.
      For 6 MV x-rays, the small GR-200 chip can be used to measure the relative
      lateral dose profiles of small fields.

PMID- 25586903
TI  - Salpingectomy as a means to reduce ovarian cancer risk.
AB  - Bilateral salpingo-oophorectomy (BSO) has become the standard-of-care for risk
      reduction in women at hereditary risk of ovarian cancer. Although this procedure
      significantly decreases both the incidence of and mortality from ovarian cancer,
      it affects quality of life, and the premature cessation of ovarian function may
      have long-term health hazards. Recent advances in our understanding of the
      molecular pathways of ovarian cancer point to the fallopian tube epithelium as
      the origin of most high-grade serous cancers (HGSC). This evolving appreciation
      of the role of the fallopian tube in HGSC has led to the consideration of
      salpingectomy alone as an option for risk management, especially in premenopausal
      women. In addition, it is postulated that bilateral salpingectomy with ovarian
      retention (BSOR), may have a public health benefit for women undergoing benign
      gynecologic surgery. In this review, we provide the rationale for salpingectomy
      as an ovarian cancer risk reduction strategy.

PMID- 25586906
TI  - Inhibitory effects of deferasirox on the structure and function of bovine liver
      catalase: a spectroscopic and theoretical study.
AB  - Deferasirox (DFX), as an oral chelator, is used for treatment of transfusional
      iron overload. In this study, we have investigated the effects of DFX as an iron
      chelator, on the function and structure of bovine liver catalase (BLC) by
      different spectroscopic methods of UV-visible, fluorescence, and circular
      dichroism (CD) at two temperatures of 25 and 37  degrees C. In vitro kinetic
      studies showed that DFX can inhibit the enzymatic activity in a competitive
      manner. KI value was calculated 39 nM according to the Lineweaver-Burk plot
      indicating a high rate of inhibition of the enzyme. Intrinsic fluorescence data
      showed that increasing the drug concentrations leads to a significant decrease in
      the intrinsic emission of the enzyme indicating a significant change in the three
      dimensional environment around the chromophores of the enzyme structure. By
      analyzing the fluorescence quenching data, it was found that the BLC has two
      binding sites for DFX and the values of binding constant at 25 and 37  degrees C
      were calculated 1.7 * 10(7) and 3 * 10(7) M(-1), respectively. The static type of
      quenching mechanism is involved in the quenching of intrinsic emission of enzyme.
      The thermodynamic data suggest that hydrophobic interactions play a major role in
      the binding reaction. UV-vis spectroscopy results represented the changes in
      tryptophan (Trp) absorption and Soret band spectra, which indicated changes in
      Trp and heme group position caused by the drug binding. Also, CD data represented
      that high concentrations of DFX lead to a significant decreasing in the content
      of beta-sheet and random coil accompanied an increasing in alpha-helical content
      of the protein. The molecular docking results indicate that docking may be an
      appropriate method for prediction and confirmation of experimental results and
      also useful for determining the binding mechanism of proteins and drugs.
      According to above results, it can be concluded that the DFX can chelate the
      Fe(III) on the enzyme active site leading to changes in the function and
      structure of catalase which can be considered as a side effect of this drug and
      consequently has an important role in hepatic complications and fibrosis. 

PMID- 25586907
TI  - Special issue commemorating the 65th birthday of Craig A. Elmets. Introduction.

PMID- 25586908
TI  - Child obesity service provision: a cross-sectional survey of physiotherapy
      practice trends and professional needs.
AB  - This study explored current physiotherapy practice trends for management of
      children who are overweight or obese. The professional needs of physiotherapists
      working with this population were also assessed, including the perceived need for
      physiotherapy clinical guidelines for prevention and management of children with
      obesity. A cross-sectional survey design was used, with questionnaires
      purposefully distributed through 13 key physiotherapy services throughout
      Australia. Snowball sampling resulted in completed questionnaires from 64
      physiotherapists who provided services to children. Half (n=33, 52%) of
      respondents provided services specifically to overweight or obese children. Of
      those providing services, one-quarter had prior training specific to working with
      this population. Most used multi-disciplinary models (n=16, 76%) and provided
      under 5h of obesity-related services each week (n=29, 88%). Half (n=16, 49%) used
      body mass index as an outcome measure but more (n=25, 76%) used bodyweight. Only
      14 (42%) assessed motor skills. The majority of respondents (n=57, 89%) indicated
      a need for physiotherapy guidelines to best manage overweight and obese children.
      Professional development priorities included: 'Educating children and families',
      'Assessment methods' and 'Exercise prescription' for overweight and obese
      children. This data provides workforce intelligence to guide future professional
      training and inform development of clinical guidelines for physiotherapists in
      prevention and management of children with obesity and related chronic disease. 

PMID- 25586909
TI  - Cascaded optical transparency in multimode-cavity optomechanical systems.
AB  - Electromagnetically induced transparency has great theoretical and experimental
      importance in many areas of physics, such as atomic physics, quantum optics and,
      more recent, cavity optomechanics. Optical delay is the most prominent feature of
      electromagnetically induced transparency, and in cavity optomechanics, the
      optical delay is limited by the mechanical dissipation rate of sideband-resolved
      mechanical modes. Here we demonstrate a cascaded optical transparency scheme by
      leveraging the parametric phonon-phonon coupling in a multimode optomechanical
      system, where a low damping mechanical mode in the unresolved-sideband regime is
      made to couple to an intermediate, high-frequency mechanical mode in the resolved
      sideband regime of an optical cavity. Extended optical delay and higher
      transmission as well as optical advancing are demonstrated. These results provide
      a route to realize ultra-long optical delay, indicating a significant step
      towards integrated classical and quantum information storage devices. 

PMID- 25586904
TI  - Involvement of epigenetics and EMT-related miRNA in arsenic-induced neoplastic
      transformation and their potential clinical use.
AB  - Exposure to toxicants leads to cumulative molecular changes that overtime
      increase a subject's risk of developing urothelial carcinoma. To assess the
      impact of arsenic exposure at a time progressive manner, we developed and
      characterized a cell culture model and tested a panel of miRNAs in urine samples
      from arsenic-exposed subjects, urothelial carcinoma patients, and controls. To
      prepare an in vitro model, we chronically exposed an immortalized normal human
      bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a
      time-dependent manner after arsenic treatment and cellular morphology was
      changed. In a soft agar assay, colonies were observed only in arsenic-treated
      cells, and the number of colonies gradually increased with longer periods of
      treatment. Similarly, invaded cells in an invasion assay were observed only in
      arsenic-treated cells. Withdrawal of arsenic treatment for 2.5 months did not
      reverse the tumorigenic properties of arsenic-treated cells. Western blot
      analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic
      treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were downregulated
      in arsenic-exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human
      urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P =
      0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases
      from controls with high sensitivity and specificity (AUC = 0.845). Our study
      suggests that exposure to arsenic rapidly induces a multifaceted
      dedifferentiation program and miR-205 has potential to be used as a marker of
      arsenic exposure as well as a maker of early urothelial carcinoma detection.

PMID- 25586910
TI  - Achilles tendons in people with type 2 diabetes show mildly compromised
      structure: an ultrasound tissue characterisation study.
AB  - BACKGROUND: Musculotendinous overuse injuries are prevalent in people with type 2
      diabetes. Non-enzymatic glycosylation of collagen resulting in tendon stiffening
      may play a role. In this case-control study we determined whether patients with
      diabetes had poorer ultrasonographic structure in their Achilles tendons compared
      to age-matched controls. METHODS: People with type 1 diabetes or type 2 diabetes,
      and age-matched controls, had computerised ultrasound tissue characterisation of
      both Achilles tendons. In contiguous ultrasonographic images of the tendon,
      echopatterns were quantified and categorised into four echo-types. Tendon
      abnormality was quantified as sum of echo-types III+IV. Furthermore, skin
      autofluorescence (AF) of the forearm (AF-value) was gathered. RESULTS: Twenty
      four type 2 diabetes patients, 24 controls, 24 type 1 diabetes patients and 20
      controls were included. AF-value was higher in type 1 diabetes (1.55+/-0.17) than
      in their controls (1.39+/-0.18, p<0.001) and in type 2 diabetes (2.28+/-0.38)
      compared to their controls (1.84+/-0.32, p<0.001) Achilles tendons of type 2
      diabetes patients contained more echo-types III+IV (14.1+/-7.9%) than matched
      controls (8.0+/-5.4%, p<0.001). There was a trend towards a difference in echo
      types III+IV between type 1 diabetes patients (9.5+/-5.3%) and their controls
      (6.5+/-3.7%, p=0.055). In a stepwise linear regression analysis, body mass index
      (BMI) was moderately associated with tendon abnormality in patients with diabetes
      and controls (beta=0.393, p<0.001). CONCLUSIONS: Type 2, and possibly type 1,
      diabetes patients showed poorer ultrasonographic Achilles tendon structure that
      may be a risk factor for tendinopathy. Although markers for accumulation of
      advanced glycation end products were elevated in both diabetes populations, only
      BMI was associated with these abnormalities. TRIAL REGISTRATION NUMBER: NTR2209.

PMID- 25586911
TI  - Older people's perspectives on participation in physical activity: a systematic
      review and thematic synthesis of qualitative literature.
AB  - BACKGROUND: Physical inactivity accounts for 9% of all deaths worldwide and is
      among the top 10 risk factors for global disease burden. Nearly half of people
      aged over 60 years are inactive. Efforts to identify which factors influence
      physical activity behaviour are needed. OBJECTIVE: To identify and synthesise the
      range of barriers and facilitators to physical activity participation. METHODS:
      Systematic review of qualitative studies on the perspectives of physical activity
      among people aged 60 years and over. MEDLINE, EMBASE, CINAHL, PsychINFO and AMED
      were searched. Independent raters assessed comprehensiveness of reporting of
      included studies. Thematic synthesis was used to analyse the data. RESULTS: From
      132 studies involving 5987 participants, we identified six major themes: social
      influences (valuing interaction with peers, social awkwardness, encouragement
      from others, dependence on professional instruction); physical limitations (pain
      or discomfort, concerns about falling, comorbidities); competing priorities;
      access difficulties (environmental barriers, affordability); personal benefits of
      physical activity (strength, balance and flexibility, self-confidence,
      independence, improved health and mental well-being); and motivation and beliefs
      (apathy, irrelevance and inefficacy, maintaining habits). CONCLUSIONS: Some older
      people still believe that physical activity is unnecessary or even potentially
      harmful. Others recognise the benefits of physical activity, but report a range
      of barriers to physical activity participation. Strategies to enhance physical
      activity participation among older people should include (1) raising awareness of
      the benefits and minimise the perceived risks of physical activity and (2)
      improving the environmental and financial access to physical activity
      opportunities.

PMID- 25586912
TI  - Concussion in youth rugby union and rugby league: a systematic review.
AB  - BACKGROUND: Children and adolescents who play rugby are at increased risk of
      concussion and its effects. Competitive rugby union and rugby league feature as
      major sports in the school sport curriculum in the UK. There is a need for a
      thorough understanding of the epidemiology of concussion in youth rugby, the
      mechanisms involved in injuries and predisposing risk factors. DATA SOURCES: The
      publication databases Pubmed, Embase and SportDISCUS were searched in April 2014
      for primary research studies of child and adolescent rugby union and rugby league
      (under 20 years) in English language with data on concussion injuries. The review
      was conducted within a larger all injury systematic review on rugby union and
      rugby league where key words used in the search included rugby, injury and
      concussion with child, adolescent, paediatric and youth. RESULTS: There were 25
      studies retrieved with data on child or adolescent rugby and concussion, 20 were
      on rugby union, three on rugby league and in two the code of rugby was
      unspecified. There was significant heterogeneity in the definitions of injuries
      and of concussion. The incidence of child and adolescent match concussion ranged
      from 0.2 to 6.9 concussions per 1000 player-hours for rugby union and was 4.6 and
      14.7 concussions per 1000 player-hours for rugby league, equivalent to a
      probability of between 0.3% and 11.4% for rugby union and of 7.7% and 22.7% for
      rugby league. CONCLUSIONS: There is a significant risk of concussion in children
      and adolescents playing rugby union and rugby league evident from the studies
      included in this systematic review. There is a need for reliable data through
      routine monitoring and reporting in schools and clubs and in hospital emergency
      departments in order to inform prevention. Concussion protocols should be
      implemented and tested.

PMID- 25586913
TI  - Patient-Reported Outcome (PRO) questionnaires for young to middle-aged adults
      with hip and groin disability: a systematic review of the clinimetric evidence.
AB  - BACKGROUND/AIM: To recommend Patient-Reported Outcome (PRO) questionnaires to
      measure hip and groin disability in young-aged to middle-aged adults. METHODS: A
      systematic review was performed in June 2014. The methodological quality of the
      studies included was determined using the COnsensus-based Standards for the
      selection of health Measurement INstruments list (COSMIN) together with
      standardised evaluations of measurement properties of each PRO. RESULTS: Twenty
      studies were included. Nine different questionnaires for patients with hip
      disability, and one for hip and groin disability, were identified. Hip And Groin
      Outcome Score (HAGOS), Hip Outcome Score (HOS), International Hip Outcome Tool-12
      (IHOT-12) and IHOT-33 were the most thoroughly investigated PROs and studies
      including these PROs reported key aspects of the COSMIN checklist. HAGOS and IHOT
      12 were based on studies with the least ratings of poor study methodology (23%
      and 31%, respectively), whereas IHOT-33 and HOS had a somewhat larger
      distribution (46%). These PROs all contain adequate measurement qualities for
      content validity (except HOS), test-retest reliability, construct validity,
      responsiveness and interpretability. No information or poor quality rating on
      methodological aspects made it impossible to fully evaluate the remaining PROs at
      present. CONCLUSIONS: HAGOS, HOS, IHOT-12 and IHOT-33 can be recommended for
      assessment of young-aged to middle-aged adults with pain related to the hip
      joint, undergoing non-surgical treatment or hip arthroscopy. At present, HAGOS is
      the only PRO also aimed for young-aged to middle-aged adults presenting with
      groin pain and is recommended for use in this population. TRIAL REGISTRATION
      NUMBER: CRD42014009995.

PMID- 25586915
TI  - Child Maltreatment and Social Connectedness Among Formerly Institutionalized
      Females: Links With Depression.
AB  - This study aimed to examine the effects of child maltreatment subtypes (physical
      abuse, sexual abuse, neglect, and exposure to domestic violence) and cumulative
      child maltreatment on depressive symptoms in adulthood, and examine the
      protective effects of social connectedness in a sample of formerly
      institutionalized females. The sample consisted of 124 females who were
      institutionalized in a Dutch juvenile justice institution during adolescence and
      were followed-up when they were on average 32 years old. Information about child
      maltreatment was extracted from treatment files. Retrospective data on social
      connectedness in young adulthood were established during interviews using a Life
      History Calendar. Relationship quality at follow-up was assessed with items
      derived from the Rochester Youth Development Study. The Center for
      Epidemiological Studies Scale for Depression (CES-D) was used to measure
      depressive symptoms in adulthood. Results showed that 85.5% of the females
      experienced child maltreatment, and co-occurrence of subtypes was high.
      Cumulative child maltreatment increased the risk of depression in adulthood.
      Furthermore, social connectedness, that is, more employment over time and the
      quality of the romantic relationship at follow-up, protected against the
      development of depression. However, social connectedness did not buffer the
      effect of maltreatment on depression. Our findings indicate that treatment of
      these girls should focus on improving the social-emotional development to promote
      positive interpersonal relationships and include educational and vocational
      components to guide these girls toward increased opportunities on the labor
      market. 

PMID- 25586916
TI  - Subjective Sleep Quality in Women With Divorce Histories: The Role of Intimate
      Partner Victimization.
AB  - A marital status of divorced or separated, as opposed to married, predicts
      increased risk of health problems, but not for all persons. Focusing on one
      established health risk that has been linked with divorce--poor subjective sleep
      quality--the present cross-sectional study examined whether a history of physical
      intimate partner victimization (IPV) helps identify divorced women at potentially
      greater risk of health problems. Community midlife women with divorce histories,
      all of whom were free of current IPV, reported on their past month sleep quality
      and lifetime IPV. The predicted odds of poor sleep quality were significantly
      greater for women with, versus without, IPV histories. This held after adjusting
      for socioemotional, medical, or sociodemographic risks. A dose-response
      relationship between IPV chronicity and poor quality sleep was observed. IPV
      history may help identify divorced women at increased risk of poor quality sleep
      and, more broadly, poor health.

PMID- 25586917
TI  - Bringing Research Into Practice: An Evaluation of Michigan's Sexual Assault Kit.
AB  - The importance of research-informed practice for the field of sexual assault has
      been stressed by academics and practitioners alike. However, there are few
      examples of researcher-practitioner partnerships in the literature, therefore
      providing minimal guidance for this process. This article describes a researcher
      practitioner partnership that was successful in using evaluation data to guide
      practice and policy decisions regarding the development and implementation of a
      new sexual assault kit for the state of Michigan. Cousins's practical
      participatory evaluation theory was used as the guiding framework for the
      evaluation. Data collection methods included focus groups with practitioners from
      five, regionally dispersed health care settings in Michigan, and surveys with
      forensic scientists throughout the state's regional laboratory system. This case
      study highlights how researchers and practitioners worked together for data
      collection, analysis, and dissemination to support research-informed practice in
      this state. Lessons learned and future recommendations for forming researcher
      practitioner partnerships to improve the response to sexual assault are
      discussed.

PMID- 25586914
TI  - Prospective Study of the Mental Health Consequences of Sexual Violence Among
      Women Living With HIV in Rural Uganda.
AB  - The association between sexual violence and depression is well known, but the
      temporal aspects of the association have not been well established. We analyzed
      data from a cohort of 173 HIV-positive women in rural Uganda who were interviewed
      every 3 months for a median of 1.8 years of follow-up. The method of generalized
      estimating equations (GEE) was used to model the marginal expectation of
      depression symptom severity (Hopkins Symptom Checklist for Depression), mental
      health-related quality of life (MOS-HIV Mental Health Summary), and heavy
      drinking (Alcohol Use Disorders Identification Test) as a function of self
      reported forced-sex victimization in the 3 months prior to interview. Estimates
      were adjusted for variables known to confound the association between
      victimization and mental health status. To assess any potential reciprocal
      relationships, we reversed the temporal ordering of the exposures and outcomes
      and refitted similar GEE models. In multivariable analyses, victimization was
      associated with greater depression symptom severity (b = 0.17; 95% CI = [0.02,
      0.33]) and lower mental health-related quality of life (b = -5.65; 95% CI = [
      9.34, -1.96]), as well as increased risks for probable depression (adjusted
      relative risk [ARR] = 1.58; 95% CI = [1.01, 2.49) and heavy drinking (ARR = 3.99;
      95% CI = [1.84, 8.63]). We did not find strong evidence of a reciprocal
      relationship. Our findings suggest that forced sex is associated with adverse
      mental health outcomes among HIV-positive women in rural Uganda. Given the
      substantial mental health-related impacts of victimization, effective health
      sector responses are needed.

PMID- 25586918
TI  - Effect of adding nano-titanium dioxide on the microstructure, mechanical
      properties and in vitro bioactivity of a freeze cast merwinite scaffold.
AB  - In the present research, merwinite (M) scaffolds with and without nano-titanium
      dioxide (titania) were synthesized by water-based freeze casting method. Two
      different amounts (7.5 and 10 wt%) of n-TiO2 were added to M scaffolds. They were
      sintered at temperature of 1573.15 degrees K and at cooling rate of 4 degrees
      K/min. The changes in physical and mechanical properties were investigated. The
      results showed that although M and M containing 7.5 wt% n-TiO2 (MT7.5) scaffolds
      had approximately the same microstructures in terms of pore size and wall
      thickness, these factors were different for sample MT10. In overall, the
      porosity, volume and linear shrinkage were decreased by adding different weight
      ratios of n-TiO2 into the M structure. According to the obtained mechanical
      results, the optimum mechanical performance was related to the sample MT7.5 (E =
      51 MPa and sigma = 2 MPa) with respect to the other samples, i.e.: M (E = 47 MPa
      and sigma = 1.8 MPa) and MT10 (E = 32 MPa and sigma = 1.4 MPa). The acellular in
      vitro bioactivity experiment confirmed apatite formation on the surfaces of all
      samples for various periods of soaking time. Based on cell study, the sample
      which possessed favorable mechanical behavior (MT7.5) supported attachment and
      proliferation of osteoblastic cells. These results revealed that the MT7.5
      scaffold with improved mechanical and biological properties could have a
      potential to be used in bone substitute.

PMID- 25586919
TI  - Performance potential and limit of MoS2 transistors.
AB  - High-performance MoS2 transistors scaled down to 100 nm are studied at various
      temperatures down to 20 K, where a highest drive current of 800 MUA MUm(-1) can
      be achieved. Extremely low electrical noise of 2.8 * 10(-10) MUm(2) Hz(-1) at 10
      Hz is also achieved at room temperature. Furthermore, a negative differential
      resistance behavior is experimentally observed and its origin of self-heating is
      identified using pulsed-current-voltage measurements. 

PMID- 25586920
TI  - Effects of Hemodialysis on Tei Index: Comparison between Flow Doppler and Tissue
      Doppler Imaging.
AB  - OBJECTIVE: Myocardial performance index (MPI, Tei index) has been described as a
      noninvasive measurement of left ventricle (LV) function. Our aim was to
      investigate the influence of preload on the LV MPI obtained by pulsed-wave tissue
      Doppler imaging (PWTDI) and determined by flow Doppler waveforms in patients with
      end-stage chronic renal failure (CRF). The second aim of this study was to
      investigate the relationship between the Tei indices obtained by both methods.
      METHODS: Eighty-four patients on regular hemodialysis (HD) treatment were
      included (mean age of 45.3 +/- 14.5 years). Standard echocardiographic
      measurements, the Tei indices obtained by conventional flow Doppler and PWTDI
      methods, mitral inflow velocities, and mitral lateral annulus tissue Doppler
      velocities were measured immediately before and after hemodialysis. RESULTS:
      After HD, weight loss in patients was significantly revealed (predialysis 63.6 +/
      13.3 kg; postdialysis 60.9 +/- 13.0 kg; P < 0.001). Left ventricle and left
      atrium diameters were significantly decreased after HD. Transmitral E and A
      velocities decreased after HD. Although Tei index measuring by conventional flow
      Doppler method significantly increased, Tei index measuring by PWTDI did not
      change after HD. CONCLUSIONS: The conventional flow Doppler-derived LV Tei index
      is influenced by hemodialysis. However, PWTDI-derived LV Tei index is not
      influenced by hemodialysis. The loading status of a patient should be taken into
      account during the application of the Tei index to the evaluation of myocardial
      performance.

PMID- 25586922
TI  - A Novel Immunoreagent for the Specific and Sensitive Detection of the Explosive
      Triacetone Triperoxide (TATP).
AB  - Triacetone triperoxide (TATP) is a primary explosive, which was used in various
      terrorist attacks in the past. For the development of biosensors, immunochemical
      u-TAS, electronic noses, immunological test kits, or test strips, the
      availability of antibodies of high quality is crucial. Recently, we presented the
      successful immunization of mice, based on the design, synthesis, and conjugation
      of a novel TATP derivative. Here, the long-term immunization of rabbits is shown,
      which resulted in antibodies of extreme selectivity and more than 1,000 times
      better affinity in relation to the antibodies from mice. Detection limits below
      10 ng L-1 (water) were achieved. The working range covers more than four decades,
      calculated from a precision profile. The cross-reactivity tests revealed an
      extraordinary selectivity of the antibodies-not a single compound could be
      identified as a relevant cross-reactant. The presented immunoreagent might be a
      major step for the development of highly sensitive and selective TATP detectors
      particularly for security applications. 

PMID- 25586921
TI  - Review of transducer principles for label-free biomolecular interaction analysis.
AB  - Label-free biomolecular interaction analysis is an important technique to study
      the chemical binding between e.g., protein and protein or protein and small
      molecule in real-time. The parameters obtained with this technique, such as the
      affinity, are important for drug development. While the surface plasmon resonance
      (SPR) instruments are most widely used, new types of sensors are emerging. These
      developments are generally driven by the need for higher throughput, lower sample
      consumption or by the need of complimentary information to the SPR data. This
      review aims to give an overview about a wide range of sensor transducers, the
      working principles and the peculiarities of each technology, e.g., concerning the
      set-up, sensitivity, sensor size or required sample volume. Starting from optical
      technologies like the SPR and waveguide based sensors, acoustic sensors like the
      quartz crystal microbalance (QCM) and the film bulk acoustic resonator (FBAR),
      calorimetric and electrochemical sensors are covered. Technologies long
      established in the market are presented together with those newly commercially
      available and with technologies in the early development stage. Finally, the
      commercially available instruments are summarized together with their sensitivity
      and the number of sensors usable in parallel and an outlook for potential future
      developments is given. 

PMID- 25586923
TI  - Determination of alanine aminotransferase with an electrochemical nano ir-C
      biosensor for the screening of liver diseases.
AB  - Alanine aminotransaminase (ALT), is an enzyme that normally resides in serum and
      body tissues, especially in the liver. It is released into the serum as a result
      of tissue injury; hence the concentration of ALT in the serum may be increased
      with acute damage to hepatic cells. A single use, disposable biosensor,
      comprising iridium nano-particle as catalyst dispersed on carbon paste, has been
      developed for the determination of ALT concentration. The biosensor is based on
      quantifying H2O2 concentration produced by a serial of ALT enzymatic reactions.
      It operates well at room temperature in different physiological fluids: phosphate
      buffer, calf serum and human serum for ALT concentration of 0-544 ng/mL.
      Experimental results in human serum are compared to those obtained by
      spectrophotometric assays with excellent agreement. Therefore, the Ir/C biosensor
      shows good relationship on the dilution of concentrated ALT clinical
      applications. 

PMID- 25586924
TI  - Polycrystalline-Diamond MEMS Biosensors Including Neural Microelectrode-Arrays.
AB  - Diamond is a material of interest due to its unique combination of properties,
      including its chemical inertness and biocompatibility. Polycrystalline diamond
      (poly-C) has been used in experimental biosensors that utilize electrochemical
      methods and antigen-antibody binding for the detection of biological molecules.
      Boron-doped poly-C electrodes have been found to be very advantageous for
      electrochemical applications due to their large potential window, low background
      current and noise, and low detection limits (as low as 500 fM). The
      biocompatibility of poly-C is found to be comparable, or superior to, other
      materials commonly used for implants, such as titanium and 316 stainless steel.
      We have developed a diamond-based, neural microelectrode-array (MEA), due to the
      desirability of poly-C as a biosensor. These diamond probes have been used for in
      vivo electrical recording and in vitro electrochemical detection. Poly-C
      electrodes have been used for electrical recording of neural activity. In vitro
      studies indicate that the diamond probe can detect norepinephrine at a 5 nM
      level. We propose a combination of diamond micro-machining and surface
      functionalization for manufacturing diamond pathogen-microsensors. 

PMID- 25586925
TI  - Invited Commentary of "Concepts in Navel Aesthetic: A Comprehensive Surface
      Anatomy Analysis".

PMID- 25586926
TI  - Role of the Cytosolic Heat Shock Protein 70 Ssa5 in the Ciliate Protozoan
      Tetrahymena thermophila.
AB  - Heat shock protein 70 (Hsp70) is a member of a family of conserved chaperone
      proteins whose function is well investigated in many model organisms. Here we
      focus on an Hsp70 called Ssa5 in the ciliate protozoan Tetrahymena thermophila,
      and reveal that its translation is heat inducible as for general Hsps. Moreover,
      the protein is abundantly expressed in the cytoplasm during sexual reproduction
      (conjugation) as well as in response to heat-stress. Knocking out of SSA5
      (DeltaSSA5) does not affect the survival of the cell under heat-stress, likely
      due to other Hsp70 paralogs compensating for the defect. During conjugation,
      DeltaSSA5 leads to a fertilization defect in which the two pronuclei are in close
      proximity but never fuse. The unfertilized pronuclei differentiate, resulting in
      a heterokaryon with developed haploid germline and somatic nuclei. In addition,
      degeneration of the parental somatic nucleus is not affected. These results
      suggest a specific involvement of Ssa5 in pronuclear fusion and fertilization. 

PMID- 25586928
TI  - Brain area-related neurological soft signs in depressive patients with different
      types of childhood maltreatment.
AB  - INTRODUCTION: This study aims to investigate the effects of childhood
      maltreatment on neurological soft signs (NSS) associated with certain brain area
      in depressive patients. METHODS: One hundred three depressive patients were
      enrolled into this study, and evaluated by Childhood Trauma Questionnaire (CTQ),
      brain area-related neurological examination scale, 24-item Hamilton Rating scale
      (HAMD24), the scale for suicidal ideation (SSI) and Beck Hopelessness Scale
      (BHS). RESULTS: Patients undergoing childhood maltreatment exhibited higher
      frontal area-related NSS scores than patients without childhood maltreatment
      experience. Patients experiencing childhood emotional or physical neglect
      displayed more frontal area-related NSS compared to their respective non
      maltreatment group. Moreover, physical neglect maltreatment caused more temporal
      area-related NSS. Patients suffering from childhood sexual abuse had more
      frontal, temporal and occipital area-related NSS than patients lacking experience
      of childhood sexual abuse. Further correlation analysis revealed that the total
      score of maltreatment positively correlated with frontal and temporal area
      related NSS score. There was a positive correlation between emotional abuse,
      emotional neglect or physical abuse and frontal area-related NSS. Physical
      neglect and sexual abuse were positively associated with the temporal area
      related NSS score. HAMD24 score was positively correlated with all brain area
      related NSS score; The SSI score correlated with three area (excluded occipital
      area)-related NSS score. The BHS score only positively correlated with frontal
      area score of NSS. Finally, no significant association was found between suicidal
      frequencies and brain area-related NSS score. DISCUSSION: Childhood maltreatment
      adversely affects the brain of depressive patients; the different maltreatment
      may impair different brain areas, especially frontal and temporal areas.

PMID- 25586927
TI  - Dysfunctional inhibitory mechanisms in locus coeruleus neurons of the wistar
      kyoto rat.
AB  - BACKGROUND: The noradrenergic nucleus locus coeruleus (LC) has functional
      relevance in several psychopathologies such as stress, anxiety, and depression.
      In addition to glutamatergic and GABAergic synaptic inputs, the activation of
      somatodendritic alpha2-adrenoceptors is the main responsible for LC activity
      regulation. The Wistar Kyoto (WKY) rat exhibits depressive- and anxiety-like
      behaviors and hyperresponse to stressors. Thus, the goal of the present study was
      to investigate in vitro the sensitivity of alpha2-adrenoceptors, as well as the
      glutamatergic and GABAergic synaptic activity on LC neurons of the WKY strain.
      METHODS: For that purpose patch-clamp whole-cell recordings were done in LC
      slices. RESULTS: The alpha2-adrenoceptors of LC neurons from WKY rats were less
      sensitive to the effect induced by the agonist UK 14 304 as compared to that
      recorded in the Wistar (Wis) control strain. In addition, the GABAergic input to
      LC neurons of WKY rats was significantly modified compared to that in Wis rats,
      since the amplitude of spontaneous GABAergic postsynaptic currents was reduced
      and the half-width increased. On the contrary, no significant alterations were
      detected regarding glutamatergic input to LC neurons between rat strains.
      CONCLUSIONS: These results point out that in WKY rats the inhibitory control
      exerted by alpha2-adrenoceptors and GABAergic input onto LC neurons is
      dysregulated. Overall, this study supports in this animal model the hypothesis
      that claims an imbalance between the glutamatergic-GABAergic systems as a key
      factor in the pathophysiology of depression.

PMID- 25586930
TI  - Tailoring plasmonic properties of gold nanohole arrays for surface-enhanced Raman
      scattering.
AB  - The wide plasmonic tuning range of nanotriangle and nanohole array patterns
      fabricated by nanosphere lithography makes them promising in surface-enhanced
      Raman scattering (SERS) sensors. Unfortunately, it is challenging to optimize
      these patterns for SERS sensing because their optical response is a complex
      mixture of localized surface plasmon resonance (SPR) and propagating surface
      plasmon polariton (SPP). In this paper, transmission and reflection measurements
      are combined with finite difference time domain simulations to identify and
      separate each plasmonic mode, discerning which resonance leads to the
      electromagnetic field enhancement. The SERS enhancement is found to be dominated
      by the absorption, which is shifted from the transmission and reflection dips
      usually used as tuning points, and by the 'gap' defects formed within the
      pattern. These effects have different spectral and geometric dependences, forming
      two optimization curves which can be used to predict the best performance for a
      given excitation wavelength. The developed model is verified with experimental
      SERS measurements for several nanohole sizes and periodicities, and then used to
      give optimal fabrication parameters for a range of measurement conditions. The
      results will promote the application of two-dimensional plasmonic nanoarrays in
      SERS sensors. 

PMID- 25586931
TI  - Treating periprosthetic joint infections as biofilms: key diagnosis and
      management strategies.
AB  - Considerable evidence suggests that microbial biofilms play an important role in
      periprosthetic joint infection (PJI) pathogenesis. Compared to free-floating
      planktonic bacteria, biofilm bacteria are more difficult to culture and possess
      additional immune-evasive and antibiotic resistance mechanisms, making infections
      harder to detect and eradicate. This article reviews cutting-edge advances in
      biofilm-associated infection diagnosis and treatment in the context of current
      PJI guidelines and highlights emerging technologies that may improve the efficacy
      and reduce costs associated with PJI. Promising PJI diagnostic tools include
      culture-independent methods based on sequence comparisons of the bacterial 16S
      ribosomal RNA gene, which offer higher throughput and greater sensitivity than
      culture-based methods. For therapy, novel methods based on disrupting biofilm
      specific properties include quorum quenchers, bacteriophages, and
      ultrasound/electrotherapy. Since biofilm infections are not easily detected or
      treated by conventional approaches, molecular diagnostic techniques and next
      generation antibiofilm treatments should be integrated into PJI clinical practice
      guidelines in the near future. 

PMID- 25586929
TI  - Distribution and antimicrobial resistance of enteric pathogens in Chinese
      paediatric diarrhoea: a multicentre retrospective study, 2008-2013.
AB  - The enteric pathogens causing diarrhoea impair children's health severely. This
      study retrospectively analysed 1577 pathogens isolated from inpatients and
      outpatients in six hospitals located in Northern (Inner Mongolia), Northeastern
      (Hebei), Eastern (Shanghai and Jiangsu), Southern (Hainan) and Central (Hubei)
      China between 2008 and 2013. Of the 1577 enteric pathogens, Salmonella presented
      with the highest frequency (36.0%), followed by diarrhoeagenic Escherichia coli
      (23.7%), Staphylococcus aureus (15.0%), Shigella (13.1%), and Aeromonas (4.6%).
      The predominant pathogens varied in different regions of China, with Salmonella
      most prevalent in Shanghai and Hainan, diarrhoeagenic E. coli most prevalent in
      Inner Mongolia, Jiangsu and Hubei, and Shigella most prevalent in Hebei. Enteric
      pathogens were more frequently isolated in males (56.9%) than in females (43.1%).
      The highest proportion of all enteric pathogens was found in infants (67.6%) with
      a peak in summer and autumn (68.5%). Antimicrobial susceptibility assay
      demonstrated that Shigella was more resistant to ampicillin, ceftriaxone and
      sulfamethoxazole than Salmonella. Of the top two serotypes in Salmonella,
      Typhimurium was more resistant to ciprofloxacin, sulfamethoxazole and
      chloramphenicol than Enteritidis (P < 0.001). Meanwhile, the resistance rates of
      Shigella flexneri against ampicillin/sulbactam, ciprofloxacin, and
      chloramphenicol were significantly higher than those of Shigella sonnei (P <
      0.001). Multidrug resistance was apparent in 58.2% of Shigella and 45.9% of
      Salmonella, and this phenomenon was more pronounced in S. flexneri. 

PMID- 25586932
TI  - Clostridium difficile infection, a descriptive analysis of solid organ transplant
      recipients at a single center.
AB  - Clostridium difficile is a bacterial enteric pathogen, which causes clinical
      disease among solid organ transplant (SOT) recipients. This large, single-center,
      retrospective study describes incidence, demographics, and impact of C. difficile
      infection (CDI) among adult SOT recipients, cardiac (n=5), lung (n=14), liver
      (n=9), renal (n=26), and multiorgan (n=9) patients transplanted and diagnosed
      with CDI (geneB PCR) between 9/2009 and 12/2012. The overall incidence of CDI in
      our population during the 40-month period of study was 4%. CDI incidence among
      cardiac, lung, liver, and renal transplant recipients was 1.9%, 7%, 2.7%, and
      3.2%, respectively (P=0.03 between organ-types). Median time from transplant to
      CDI for all was 51 (14-249) days, with liver recipients having the shortest time
      to infection, median 36 (15-101) days, and lung recipients having a longer time
      to infection, median 136 (29-611) days. Antibiotic exposure within 3 months of
      CDI was evident in 45 of the 63 (71%) patients in this study, 80%, 79%, 100%,
      58%, and 67% of cardiac, lung, liver, renal, and multiorgan transplant
      recipients, respectively. Most patients (83%) were hospitalized within the 3
      months preceding CDI. Recipients were followed for a median time of 23 (16-31)
      months; at the time of last follow-up, 83% of allografts were functioning, and
      86% of patients were alive. One death and 1 graft failure were causally related
      to CDI. CDI had an overall incidence of 4%; clinicians should have heightened
      awareness for CDI, especially among patients receiving antibiotics, with
      increased monitoring and aggressive management of CDI.

PMID- 25586933
TI  - Assessment and clinical validation of margins for adaptive simultaneous
      integrated boost in neo-adjuvant radiochemotherapy for rectal cancer.
AB  - PURPOSE: An adaptive concomitant boost (ACB) for the neo-adjuvant treatment of
      rectal cancer was clinically implemented. In this study population margins
      M(90,90) considering rectal deformation were derived for 10 consecutive patients
      treated at 18 * 2.3Gy with Helical Tomotherapy (HT) and prospectively validated
      on 20 additional patients treated with HT, delivering ACB in the last 6
      fractions. METHODS: Sectorial margins M(90,90) of the whole and second treatment
      parts were assessed for 90% population through a method combining the 90%
      coverage probability maps of rectal positions (CPC90%) with 3D local distance
      measurements between the CPC90% and a reference rectal contour. M(90,90) were
      compared with the margins M(90,90)(95%/99%), ensuring CPC90% coverage with
      95%/99% confidence level. M(90,90) of the treatment second part were chosen as
      ACB margins which were clinically validated for each patient by means of %volume
      missing of CPC5/6 excluded by the ACB margins. RESULTS: The whole treatment
      M(90,90) ranged between 1.9 mm and 9 mm in the lower-posterior and upper-anterior
      sectors, respectively. Regarding ACB, M(90,90) were 7 mm in the anterior
      direction and <5 mm elsewhere. M(90,90)(95%/99%) did not significantly differ
      from M(90,90). The %volume excluded by the ACB margin was<2% for all male and <5%
      for 9/10 female patients. The dosimetry impact on R_adapt for the patients with
      the largest residual error was negligible. CONCLUSIONS: Local deformation
      measurements confirm an anisotropic motion of rectum once set-up error is rigidly
      corrected. Margins of 7 mm anterior and 5 mm elsewhere are adequate for ACB.
      Female patients show a slightly larger residual error.

PMID- 25586934
TI  - Dynamic consent: a possible solution to improve patient confidence and trust in
      how electronic patient records are used in medical research.
AB  - With one million people treated every 36 hours, routinely collected UK National
      Health Service (NHS) health data has huge potential for medical research.
      Advances in data acquisition from electronic patient records (EPRs) means such
      data are increasingly digital and can be anonymised for research purposes. NHS
      England's care.data initiative recently sought to increase the amount and
      availability of such data. However, controversy and uncertainty following the
      care.data public awareness campaign led to a delay in rollout, indicating that
      the success of EPR data for medical research may be threatened by a loss of
      patient and public trust. The sharing of sensitive health care data can only be
      done through maintaining such trust in a constantly evolving ethicolegal and
      political landscape. We propose that a dynamic consent model, whereby patients
      can electronically control consent through time and receive information about the
      uses of their data, provides a transparent, flexible, and user-friendly means to
      maintain public trust. This could leverage the huge potential of the EPR for
      medical research and, ultimately, patient and societal benefit. 

PMID- 25586935
TI  - The role of age in association analyses of ADHD and related neurocognitive
      functioning: A proof of concept for dopaminergic and serotonergic genes.
AB  - Elucidating genetic mechanisms involved in Attention-Deficit/Hyperactivity
      Disorder (ADHD) has been challenging. Relatively unexplored is the fact that
      genetic mechanisms can differ with age. The current study explored the
      association between dopaminergic and serotonergic genes, ADHD symptoms, and
      neurocognitive functioning in relation to age. Associations of three genetic ADHD
      risk factors, DAT1, DRD4, and 5-HTT with symptoms and six neurocognitive measures
      were explored in two samples of the NeuroIMAGE study: 756 children, adolescents,
      and young adults with ADHD, their siblings, and controls (M age 17 years, SD
      3.2), and 393 parents with and without ADHD (M age 48 years, SD 4.8). Association
      analyses were performed in both samples, and effects were compared to address
      dichotomous age effects. Gene*age interactions were examined to address
      continuous age effects. Moderating effects of age were found for DRD4-7R
      carriership and ADHD symptoms in the adult group only; in the adolescents the 5
      HTT LL genotype was differentially associated with inhibition and with motor
      timing at different ages, and to inhibition in adults; DAT1 10-6 haplotype
      carriership showed differential working memory performance depending on age. None
      of our effects survived correction for multiple comparisons. Our results are
      preliminary, but may point to differential genotype-phenotype associations at
      different ages. This can be seen as a proof of concept for the importance of age
      in dopaminergic and serotonergic genetic association analyses. Our findings are
      consistent with the idea that genetic and neurocognitive mechanisms underlying
      ADHD may change throughout life. (c) 2015 Wiley Periodicals, Inc.

PMID- 25586936
TI  - Comparison of experimentally-induced wounds in rabbits treated with different
      sources of platelet-rich plasma.
AB  - Over the years, autologous platelet-rich plasma (PRP) has been used to great
      advantage in the healing of acute and chronic wounds. However, it is impossible
      to use in some situations so alternative PRPs need to be considered, such as
      homologous or heterologous PRPs. In order to evaluate the effects of PRP in the
      form of autologous, heterologous and homologous gels on in vivo cutaneous wound
      healing, 18 animals divided into three groups of six, were used for the study,
      with another six animals used as PRP donors. For the heterologous group an adult,
      mixed breed dog was used to obtain the PRP. The wounds were induced using an 8 mm
      punch. The left side was treated with NaCl 0.9%(r) (A) and a PRP gel was applied
      (GA = autologous; GHE = heterologous and GHO = homologous) on the right side (B).
      The wounds were evaluated for a period of 17 days. On the 17th day biopsies were
      taken for histopathological assessment of the wounds. The percentage of
      contraction was evident in side B (treated), which was confirmed in the
      microscopic analysis of the histological sections. Thus, it was concluded that
      PRP, regardless of the source, improves and accelerates the healing process,
      demonstrating its therapeutic potential on cutaneous lesions and its use in
      patients with impaired wound healing.

PMID- 25586937
TI  - Comparison of haematopoietic stem cell engraftment through the retro-orbital
      venous sinus and the lateral vein: alternative routes for bone marrow
      transplantation in mice.
AB  - Bone marrow transplantation in mice is performed by intravenous administration of
      haematopoietic repopulating cells, usually via the lateral tail vein. This
      technique can be technically challenging to carry out and may cause distress to
      the mice. The retro-orbital sinus is a large area where there is a confluence of
      several vessels that provides an alternative route for intravenous access. Retro
      orbital injection, although aesthetically unpleasant, can be performed rapidly
      without requiring mechanical restriction or heat-induced vasodilation. In
      addition, this technique can be easily learned by novice manipulators. This route
      of administration has been reported for use in bone marrow transplantation but
      there is no comparison of retro-orbital and tail vein injections reported for
      this specific purpose, although both routes have been compared for many other
      applications. Here, we provide for the first time a comprehensive comparison
      between tail vein and retro-orbital injections for two different bone marrow
      transplant scenarios in P3B and B6D2F1 mice. In both cases, no significant
      differences regarding donor engraftment were observed between mice transplanted
      using each of the techniques. Haematological counts and leukocyte subpopulation
      distribution were practically identical between both animal groups. Moreover,
      donor engraftment levels were less homogenous when cells were transplanted by
      tail vein injection, probably due to a higher risk of failure associated with
      this technique. All these data suggest that retro-orbital injection is a
      compelling alternative to conventional tail vein injection for bone marrow
      transplant in mice, providing similar and more homogenous haematopoietic
      reconstitution. 

PMID- 25586939
TI  - Bacterial infections following non-ablative fractional laser treatment: a case
      series and discussion.
AB  - Non-ablative fractional laser procedures have become increasingly popular since
      their introduction in 2004. The fractional 1,927 nm thulium laser is a non
      ablative device that penetrates up to 300 MUm in the skin and the 1,550 nm
      erbium:glass laser penetrates up to 1,400 MUm. These procedures are considered
      minimally invasive with a high safety profile; therefore, infectious
      complications are exceedingly rare. However, we report five recent cases of
      bacterial infection with both gram-positive and gram-negative organisms following
      treatment with the fractional 1550/1927 nm laser approximately 1 day to 1 week
      post-procedure. One patient had a rapidly progressing pustular eruption with
      symptoms of sepsis. These patients were seen immediately, cultures were obtained
      and empiric antibiotic therapy was initiated. They recovered without long-term
      complications. Rapid-onset bacterial infections following non-ablative laser
      resurfacing with the 1550/1927 nm laser have not been previously reported in the
      literature. The infections can progress quickly and lead to serious sequelae,
      including systemic illness and severe scarring, if not identified and
      appropriately treated. We present these cases to highlight the importance of
      close surveillance and when appropriate, rapid intervention, following non
      ablative fractional procedures, especially when patients present with atypical
      symptoms and signs.

PMID- 25586938
TI  - Dynamic laryngeal narrowing during exercise: a mechanism for generating intrinsic
      PEEP in COPD?
AB  - INTRODUCTION: Patients with COPD commonly exhibit pursed-lip breathing during
      exercise, a strategy that, by increasing intrinsic positive end-expiratory
      pressure, may optimise lung mechanics and exercise tolerance. A similar role for
      laryngeal narrowing in modulating exercise airways resistance and the respiratory
      cycle volume-time course is postulated, yet remains unstudied in COPD. The aim of
      this study was to assess the characteristics of laryngeal narrowing and its role
      in exercise intolerance and dynamic hyperinflation in COPD. METHODS: We studied
      19 patients (n=8 mild-moderate; n=11 severe COPD) and healthy age and sex matched
      controls (n=11). Baseline physiological characteristics and clinical status were
      assessed prior to an incremental maximal cardiopulmonary exercise test with
      continuous laryngoscopy. Laryngeal narrowing measures were calculated at the
      glottic and supra-glottic aperture at rest and peak exercise. RESULTS: At rest,
      expiratory laryngeal narrowing was pronounced at the glottic level in patients
      and related to FEV1 in the whole cohort (r=-0.71, p<0.001) and patients alone (r=
      0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak
      ventilation in all subjects (r=-0.55, p=0.0015) and patients (r=-0.71, p<0.001)
      and peak exercise tidal volume (r=-0.58, p=0.0062 and r=-0.55, p=0.0076,
      respectively). Exercise glottic narrowing was also inversely related to peak
      oxygen uptake (% predicted) in all subjects (r=-0.65, p<0.001) and patients
      considered alone (r=-0.58, p=0.014). Exercise inspiratory duty cycle was related
      to exercise glottic narrowing for all subjects (r=-0.69, p<0.001) and patients
      (r=-0.62, p<0.001). CONCLUSIONS: Dynamic laryngeal narrowing during expiration is
      prevalent in patients with COPD and is related to disease severity, respiratory
      duty cycle and exercise capacity.

PMID- 25586940
TI  - Organic synthesis: march of the machines.
AB  - Organic synthesis is changing; in a world where budgets are constrained and the
      environmental impacts of practice are scrutinized, it is increasingly recognized
      that the efficient use of human resource is just as important as material use.
      New technologies and machines have found use as methods for transforming the way
      we work, addressing these issues encountered in research laboratories by enabling
      chemists to adopt a more holistic systems approach in their work. Modern
      developments in this area promote a multi-disciplinary approach and work is more
      efficient as a result. This Review focuses on the concepts, procedures and
      methods that have far-reaching implications in the chemistry world. Technologies
      have been grouped as topics of opportunity and their recent applications in
      innovative research laboratories are described. 

PMID- 25586941
TI  - Relationship of Troponin T and Age- and Sex-Adjusted BNP Elevation Following
      Subarachnoid Hemorrhage with 30-Day Mortality.
AB  - BACKGROUND: Troponin and brain natriuretic peptide (BNP) levels are predictors of
      mortality following subarachnoid hemorrhage (SAH). Prior studies used strict
      cutoffs for BNP elevation; however, normal levels of BNP are increased in older
      persons and women. We explored the association of troponin elevation and BNP
      elevation adjusted for sex and age with 30-day mortality. METHODS: In this
      retrospective cohort study of patients with SAH, collected data included peak
      troponin T and BNP levels. Mortality data were obtained from inpatient mortality
      data and available records. Troponin T elevation was defined as more than 0.10
      ng/mL; BNP elevation was defined as greater than the 95th percentile reference
      limit by age and sex for patients without cardiovascular disease. Associations of
      elevated troponin T and BNP were estimated from a log-binomial regression model
      reporting relative risks (RRs), 95 % CIs, and P values; missing data were imputed
      with the sample median or most frequent category. RESULTS: This study included
      175 SAH patients. In single-variable analysis, peak troponin T level greater than
      0.10 ng/mL was associated with increased risk in 30-day mortality (RR 4.38; 95 %
      CI 2.43-7.89; P < .001); there was no association with elevated peak BNP adjusted
      for age and sex (RR 1.13; 95 % CI 0.55-2.35; P = .74). There was no evidence
      suggesting that the combination of elevated peak BNP and elevated peak troponin
      increased the risk of 30-day mortality. CONCLUSIONS: Elevated troponin was an
      independent predictor of 30-day mortality following SAH; however, when adjusted
      for age and sex, elevations in BNP did not have this association.

PMID- 25586942
TI  - Abnormal shape of the cavum septi pellucidi: an indirect sign of partial agenesis
      of the corpus callosum.
AB  - OBJECTIVE: To describe and assess the presence of a new indirect sign of partial
      agenesis of the corpus callosum (pACC): an abnormally shaped cavum septi
      pellucidi (CSP). METHODS: We analyzed retrospectively images from all 71 cases of
      pACC seen at two referral centers between September 2006 and April 2014.
      Abnormally shaped CSP was diagnosed when its lateral dimension was greater than
      its anteroposterior dimension in the axial transthalamic plane, and the incidence
      of this sign was assessed. We also examined the following variables: gestational
      age at referral, indication for referral, which (if any) of the four corpus
      callosal segments were abnormal, presence of other, previously established,
      indirect signs of callosal agenesis (ACC) and presence of additional cerebral or
      extracerebral anomalies. RESULTS: In 56 of the 71 (79%) cases, the CSP was
      measurable; it was abnormally shaped in 19 (34%) of these cases, 15 (79%) of
      which had no other indirect signs of pACC. Of 23 cases with isolated pACC and no
      other indirect signs, 12 (52%) had an abnormally shaped CSP. CONCLUSIONS: In a
      significant proportion of cases of pACC detected prenatally, the shape of the CSP
      is abnormal. This should be considered an additional indirect sign of pACC, and
      is frequently the only clue to the diagnosis. When observing this sign in a
      screening context, pACC should be considered, and an attempt to visualize the
      corpus callosum directly in the midsagittal plane is suggested.

PMID- 25586944
TI  - MicroRNA and targeted mRNA expression profiling analysis in human colorectal
      adenomas and adenocarcinomas.
AB  - BACKGROUND: Colorectal cancer (CRC) mainly develops from colorectal adenomas
      (CRAs). MicroRNAs (miRs) are short non-coding transcripts that regulate gene
      expression by binding to target mRNAs, preventing their expression. It was
      suggested that miRs were involved in cancer as tumour suppressors or oncogenes,
      thereby being also potential cancer biomarkers. We conducted an expression
      analysis of miRNAs and several of their target mRNAs, by using microarrays and
      quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR) (RT-qPCR),
      in CRA and CRC, as compared to normal mucosa (NOR), in order to identify
      candidate miRNAs involved in CRC progression. RESULTS: Microarray, together with
      confirmatory RT-qPCR analyses, showed 17 significantly deregulated miRNAs in
      colorectal lesions. While, as expected, some miRNAs have been previously reported
      to be associated with CRC, including miR-21 and miR-145, others were new (miR
      125a-5p and miR-320 family). Some miRNAs were specific for the CRC versus NOR
      comparison (miR-320b), or for the CRA versus NOR comparison (miR-15b or miR-16),
      but several of them (miR-21, miR-24, miR-145, mir-150, miR-378) were deregulated
      in both CRAs and CRCs, as compared to NOR. The impact of these changes in miR
      expression on target genes is suggested by the associated deregulation of these
      genes in CRA and CRC. CONCLUSIONS: We confirmed that several miRNAs were
      abnormally expressed in colorectal lesions, identified new deregulated miRs, and
      showed that several miRNAs could mark the transition from NOR to CRA, thereby
      marking progression from the early steps of cancer.

PMID- 25586945
TI  - The association between alcohol use and engagement in casual sexual relationships
      and experiences: a meta-analytic review of non-experimental studies.
AB  - The present study provides a meta-analytic review of the association between
      alcohol use and engagement in casual sexual relationships and experiences
      (CSREs). Specifically, the meta-analysis focused on non-experimental studies of
      community and college samples. Results from the meta-analysis, which included 29
      relevant studies (34 effect sizes), indicated that alcohol use was significantly
      associated with engaging in CSREs, r = .34, 95 % CI [.29-.38], but that this link
      showed considerable variability. Subsequent analyses examined moderators that may
      explain this heterogeneity. Results revealed that age and method of assessment
      significantly moderated the effect of alcohol use on CSRE engagement such that
      the association was greater for emerging adults (18-24 year olds) than older
      adults and online assessments produced greater effect sizes than paper-and-pencil
      assessments. These results have implications for future research and intervention
      development. In particular, this meta-analysis emphasizes the need for studies
      that utilize consistent measurements of CSRE engagement, include diverse
      methodology, and expand upon sampling.

PMID- 25586943
TI  - Ion and molecular recognition using aryl-ethynyl scaffolding.
AB  - The aryl-ethynyl linkage has been extensively employed in the construction of
      hosts for a variety of guests. Uses range from ion detection (e.g., of metal
      cations in the environment or industrial waste and of anions prevalent in
      nature), to molecular mimics for biological systems, and to applications
      targeting future safety issues (such as CO2 capture and indicators for the
      manufacture of chemical weapons). This Focus Review examines the utilization of
      the aryl-ethynyl linkage in engineering host molecules for a variety of different
      guests, and how the alkyne unit plays an integral part as both a rigid
      scaffolding section in host geometry design as well as a linker to allow
      conjugative communication between discrete pi-electron systems. 

PMID- 25586946
TI  - Pediatric cochlear implantation in residual hearing candidates.
AB  - OBJECTIVES: To propose categories for the various types of residual hearing in
      children and to review the outcomes of cochlear implantation (CI) in children
      with these different hearing conditions. METHODS: We identified 53 children with
      residual hearing who had received a cochlear implant. Five groups were
      arbitrarily defined based on auditory features: G1, characterized by low
      frequency residual hearing (n=5); G2, characterized by severe sensorineural
      hearing loss (SNHL) and low speech discrimination (n=12); G3, characterized by
      asymmetric SNHL (n=9); G4, characterized by progressive SNHL (n=15); and G5,
      characterized by fluctuating SNHL (n=12). The main audiometric features and
      outcomes of the groups were analyzed. RESULTS: The mean age at implantation was
      10.15 years (range, 2.5-21 years). The mean preoperative score for the
      discrimination of open-set words was 48%; this score increased to 74% at 12
      months and 81% at 24 months after the CI procedure (G1 to G5, respectively:
      79/62/77%, 50/81/88%, 59/75/86%, 35/74/67%, and 39/69/80%). Children who were
      implanted after 10 years of age did not improve as much as those who were
      implanted at a younger age (open-set word list speech perception [OSW] score at
      12 months: 62% vs 83%; P=.0009). Shorter delays before surgery were predictive of
      better performance (P=.003). Inner ear malformation and SLC26A4 mutations were
      not predictive of the outcome. CONCLUSIONS: CIs provide better results compared
      with hearing aids in children with residual hearing. Factors that may impact the
      benefits of CIs in patients with residual hearing are age, delay in performing
      the CI procedure, which ear is implanted, and initial underestimation of the
      patient's hearing difficulties.

PMID- 25586947
TI  - Reliability of the penetration aspiration scale with flexible endoscopic
      evaluation of swallowing.
AB  - OBJECTIVES: The Penetration Aspiration Scale (PAS), although designed for
      videofluoroscopy, has been utilized with flexible endoscopic evaluation of
      swallowing (FEES) in both research and clinical practice. The purpose of this
      investigation was to determine inter- and intrarater reliability of the PAS with
      FEES as a function of clinician FEES experience and retest interval. METHODS:
      Three groups of 3 clinicians (N=9) with varying FEES experience (beginning,
      intermediate, and advanced) assigned PAS scores to 35 swallows. Initial ratings
      were repeated following short-term (ie, 1 day) and long-term (ie, 1 week) retest
      intervals. RESULTS: Intraclass correlation coefficients were calculated to assess
      interrater reliability on the first rating for each group. The coefficients were
      .91, .82, and .89 for the beginning, intermediate, and advanced clinicians,
      respectively. Overall interrater reliability across all 9 clinicians,
      irrespective of experience, was .85. Intraclass correlation coefficients were
      also calculated to assess intrarater reliability. The intrarater reliability for
      short- and long-term ratings was .90, .94, and .96 and .96, .97, and .94 for the
      beginning, intermediate, and advanced clinicians, respectively. Overall
      intrarater reliability across all 9 clinicians and all 3 ratings was .94.
      CONCLUSIONS: Excellent inter- and intrarater reliability was evidenced with the
      application of the PAS for FEES regardless of clinician experience and retest
      interval.

PMID- 25586948
TI  - Hearing in static unilateral vestibular schwannoma declines more than in the
      contralateral ear.
AB  - OBJECTIVE: To determine the effect of static vestibular schwannomas on hearing.
      STUDY DESIGN: Retrospective review of audiometric measures in 15 patients with
      documented nongrowth of internal auditory canal and cerebellopontine angle
      enhancing masses. METHODS: Data from patients seen in an ambulatory tertiary care
      setting between the years of 2002 and 2012 with a diagnosis of acoustic neuroma
      or vestibular schwannoma were reviewed. Exclusion criteria included preexisting
      otologic disease, prior therapy for the schwannoma, and tumor growth. Radiology
      reports were reviewed to ensure nongrowth and were confirmed by taking magnetic
      resonance imaging (MRI) measurements ourselves. Audiologic measurements included
      pure tone average, enhanced pure tone average (average of .5, 1, 2, and 4 KHz
      thresholds), 4 KHz threshold, 8 KHz threshold, and speech discrimination. The
      data were analyzed using mixed effect model with unstructured variance-covariance
      structure. RESULTS: Difference in audiometric measures between ears significantly
      (P<.05) increased for all measures except 8 KHz. CONCLUSION: Spontaneous decline
      in hearing relative to time is exaggerated in the affected ear despite no
      vestibular schwannoma growth. This finding can be useful for patient counseling
      and treatment decision making.

PMID- 25586953
TI  - This year and this issue.

PMID- 25586951
TI  - Stereotactic body radiotherapy and treatment at a high volume facility is
      associated with improved survival in patients with inoperable stage I non-small
      cell lung cancer.
AB  - BACKGROUND: This study examined the comparative effectiveness of no treatment
      (NoTx), conventional fractionated radiotherapy (ConvRT), and stereotactic body
      radiotherapy (SBRT) in patients with inoperable stage I non-small cell lung
      cancer. This population based cohort also allowed us to examine what facility
      level characteristics contributed to improved outcomes. METHODS: We included
      patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0
      inoperable lung cancer (n=13,036). Overall survival (OS) was estimated using
      Kaplan-Meier methods and Cox proportional hazard regression. RESULTS: The median
      follow up was 68months (interquartile range: 35-83months) in surviving patients.
      Among the cohort, 52% received NoTx, 41% received ConvRT and 6% received SBRT.
      The 3-year OS was 28% for NoTx, 36% for ConvRT radiotherapy, and 48% for the SBRT
      cohort (p<0.0001). On multivariate analysis, the hazard ratio for SBRT and ConvRT
      were 0.67 and 0.77, respectively, as compared to NoTx (1.0 ref) (p<0.0001).
      Patients treated at a high volume facility vs. low volume facility had a hazard
      ratio of 0.94 vs. 1.0 (p=0.01). CONCLUSIONS: Patients with early stage inoperable
      lung cancer treated with SBRT and at a high volume facility had a survival
      benefit compared to patients treated with ConvRT or NoTx or to those treated at a
      low volume facility.

PMID- 25586954
TI  - What's new about NATA?

PMID- 25586952
TI  - Safety of dose escalation by simultaneous integrated boosting radiation dose
      within the primary tumor guided by (18)FDG-PET/CT for esophageal cancer.
AB  - PURPOSE: To observe the safety of selective dose boost to the pre-treatment high
      (18)F-deoxyglucose (FDG) uptake areas of the esophageal GTV. METHODS: Patients
      with esophageal squamous cell carcinoma were treated with escalating radiation
      dose of 4 levels, with a simultaneous integrated boost (SIB) to the pre-treatment
      50% SUVmax area of the primary tumor. Patients received 4 monthly cycles of
      cisplatin and fluorouracil. Dose-limiting toxicity (DLT) was defined as any Grade
      3 or higher acute toxicities causing continuous interruption of radiation for
      over 1 week. RESULTS: From April 2012 to February 2014, dose has been escalated
      up to LEVEL 4 (70Gy). All of the 25 patients finished the prescribed dose without
      DLT, and 10 of them developed Grade 3 acute esophagitis. One patient of LEVEL 2
      died of esophageal hemorrhage within 1 month after completion of radiotherapy,
      which was not definitely correlated with treatment yet. Late toxicities remained
      under observation. With median follow up of 8.9months, one-year overall survival
      and local control was 69.2% and 77.4%, respectively. CONCLUSIONS: Dose escalation
      in esophageal cancer based on (18)FDG-PET/CT has been safely achieved up to 70Gy
      using the SIB technique. Acute toxicities were well tolerated, whereas late
      toxicities and long-term outcomes deserved further observation.

PMID- 25586955
TI  - Blood transfusion at the time of the First World War--practice and promise at the
      birth of transfusion medicine.
AB  - The centenary of the start of the First World War has stirred considerable
      interest in the political, social, military and human factors of the time and how
      they interacted to produce and sustain the material and human destruction in the
      4 years of the war and beyond. Medical practice may appear distant and static and
      perhaps seems to have been somewhat ineffectual in the face of so much trauma and
      in the light of the enormous advances in medicine and surgery over the last
      century. However, this is an illusion of time and of course medical, surgical and
      psychiatric knowledge and procedures were developing rapidly at the time and the
      war years accelerated implementation of many important advances. Transfusion
      practice lay at the heart of resuscitation, and although direct transfusion from
      donor to recipient was still used, Geoffrey Keynes from Britain, Oswald Robertson
      from America and his namesake Lawrence Bruce Robertson from Canada, developed
      methods for indirect transfusion from donor to recipient by storing blood in
      bottles and also blood-banking that laid the foundation of modern transfusion
      medicine. This review explores the historical setting behind the development of
      blood transfusion up to the start of the First World War and on how they
      progressed during the war and afterwards. A fresh look may renew interest in how
      a novel medical speciality responded to the needs of war and of post-war society.

PMID- 25586956
TI  - Profound sustained reticulocytopenia and anaemia in an adult patient with sickle
      cell disease.

PMID- 25586958
TI  - Osteonecrosis of the Jaw in Patients With Metastatic Renal Cell Cancer Treated
      With Bisphosphonates and Targeted Agents: Results of an Italian Multicenter Study
      and Review of the Literature.
AB  - Osteonecrosis of the jaw (ONJ) associated with the use of bisphosphonates has
      been rarely reported in metastatic renal cell cancer (RCC) patients. Since the
      introduction of combined therapies consisting of nitrogen-containing
      bisphosphonates (NBPs) and targeted agents, an increasing number of RCC patients
      were reported to develop ONJ, suggesting that therapeutic angiogenesis
      suppression might increase the risk of ONJ in NBPs users. We performed a
      multicenter retrospective study and reviewed literature data to assess the
      occurrence and to investigate the nature of ONJ in RCC patients taking NBPs and
      targeted agents. Nine Italian Centers contributed to the data collection.
      Patients with exposed and nonexposed ONJ were eligible for the study if they had
      been taking NBPs and were receiving targeted agents at the time of ONJ diagnosis.
      Forty-four RCC patients were studied. Patients were mostly male (82%), with a
      median age of 63 years (range, 45-85 years). Zoledronic acid (93%) and sunitinib
      (80%) were the most frequently used NBP and antiangiogenic agent, respectively.
      Other agents included Pamidronate, ibandronate, sorafenib, bevacizumab, mammalian
      target of rapamycin inhibitors. Forty-nine sites of ONJ were encountered, with
      the mandible being the preferred site of ONJ (52%); both jaws were affected in 5
      cases (12%). The most common precipitating event was dental/periodontal infection
      (34%), followed by tooth extraction (30%). Oral triggers of ONJ were missing in
      10 cases (23%). This unexpectedly high number of ONJ cases, in comparison with
      literature data, suggests that frequency of ONJ in RCC patients might be largely
      underestimated and suggests a potential role for targeted agents in the
      incremental risk of ONJ. 

PMID- 25586959
TI  - Multimodal neuroimaging evidence linking memory and attention systems during
      visual search cued by context.
AB  - Visual search can be facilitated by the learning of spatial configurations that
      predict the location of a target among distractors. Neuropsychological and
      functional magnetic resonance imaging (fMRI) evidence implicates the medial
      temporal lobe (MTL) memory system in this contextual cueing effect, and
      electroencephalography (EEG) studies have identified the involvement of visual
      cortical regions related to attention. This work investigated two questions: (1)
      how memory and attention systems are related in contextual cueing; and (2) how
      these systems are involved in both short- and long-term contextual learning. In
      one session, EEG and fMRI data were acquired simultaneously in a contextual
      cueing task. In a second session conducted 1 week later, EEG data were recorded
      in isolation. The fMRI results revealed MTL contextual modulations that were
      correlated with short- and long-term behavioral context enhancements and
      attention-related effects measured with EEG. An fMRI-seeded EEG source analysis
      revealed that the MTL contributed the most variance to the variability in the
      attention enhancements measured with EEG. These results support the notion that
      memory and attention systems interact to facilitate search when spatial context
      is implicitly learned. 

PMID- 25586961
TI  - Toxicity of the conventional energetics TNT and RDX relative to new insensitive
      munitions constituents DNAN and NTO in Rana pipiens tadpoles.
AB  - An initiative within the US military is targeting the replacement of traditional
      munitions constituents with insensitive munitions to reduce risk of accidental
      detonation. The purpose of the present study was to comparatively assess toxicity
      of the traditional munitions constituents 2,4,6-trinitrotoluene (TNT) and 1,3,5
      trinitroperhydro-1,3,5-triazine (RDX) with the new insensitive munitions
      constituents 2,4-dinitroanisole (DNAN) and 3-nitro-1,2,4-triazol-5-one (NTO). The
      following exposure durations were performed with Rana pipiens (leopard frog)
      tadpoles: TNT and DNAN, 96 h and 28 d; RDX, 10 d and 28 d; NTO, 28 d. The 96-h
      50% lethal concentration (LC50) values and 95% confidence intervals for TNT and
      DNAN were 4.4 mg/L (4.2 mg/L, 4. 7 mg/L) and 24.3 mg/L (21.3 mg/L, 27.6 mg/L),
      respectively. No significant impacts on survival were observed in the 10-d
      exposure to RDX up to 25.3 mg/L. Effects on tadpole swimming distance were
      observed with a lowest-observed-effect concentration (LOEC) of 5.9 mg/L RDX. In
      the 28-d exposures, the LOECs for survival for TNT, DNAN, and NTO were 0.003
      mg/L, 2.4 mg/L, and 5.0 mg/L, respectively. No significant mortality was observed
      in the RDX chronic 28-d exposure up to the highest treatment level tested of 28.0
      mg/L. Neither tadpole developmental stage nor growth was significantly affected
      in any of the 28-d exposures. Rana pipiens were very sensitive to chronic TNT
      exposure, with an LOEC 3 orders of magnitude lower than those for insensitive
      munitions constituents DNAN and NTO.

PMID- 25586963
TI  - Erratum to: Role of sirtuins in chronic obstructive pulmonary disease.

PMID- 25586960
TI  - Pak2 regulates hematopoietic progenitor cell proliferation, survival, and
      differentiation.
AB  - p21-Activated kinase 2 (Pak2), a serine/threonine kinase, has been previously
      shown to be essential for hematopoietic stem cell (HSC) engraftment. However,
      Pak2 modulation of long-term hematopoiesis and lineage commitment remain
      unreported. Using a conditional Pak2 knockout mouse model, we found that
      disruption of Pak2 in HSCs induced profound leukopenia and a mild macrocytic
      anemia. Although loss of Pak2 in HSCs leads to less efficient short- and long
      term competitive hematopoiesis than wild-type cells, it does not affect HSC self
      renewal per se. Pak2 disruption decreased the survival and proliferation of
      multicytokine stimulated immature progenitors. Loss of Pak2 skewed lineage
      differentiation toward granulocytopoiesis and monocytopoiesis in mice as
      evidenced by (a) a three- to sixfold increase in the percentage of peripheral
      blood granulocytes and a significant increase in the percentage of granulocyte
      monocyte progenitors in mice transplanted with Pak2-disrupted bone marrow (BM);
      (b)Pak2-disrupted BM and c-kit(+) cells yielded higher numbers of more mature
      subsets of granulocyte-monocyte colonies and polymorphonuclear neutrophils,
      respectively, when cultured in the presence of granulocyte-macrophage colony
      stimulating factor. Pak2 disruption resulted, respectively, in decreased and
      increased gene expression of transcription factors JunB and c-Myc, which may
      suggest underlying mechanisms by which Pak2 regulates granulocyte-monocyte
      lineage commitment. Furthermore, Pak2 disruption led to (a) higher percentage of
      CD4(+) CD8(+) double positive T cells and lower percentages of CD4(+) CD8(-) or
      CD4(-) CD8(+) single positive T cells in thymus and (b) decreased numbers of
      mature B cells and increased numbers of Pre-Pro B cells in BM, suggesting defects
      in lymphopoiesis.

PMID- 25586962
TI  - Gene pyramiding enhances durable blast disease resistance in rice.
AB  - Effective control of blast, a devastating fungal disease of rice, would increase
      and stabilize worldwide food production. Resistance mediated by quantitative
      trait loci (QTLs), which usually have smaller individual effects than R-genes but
      confer broad-spectrum or non-race-specific resistance, is a promising alternative
      to less durable race-specific resistance for crop improvement, yet evidence that
      validates the impact of QTL combinations (pyramids) on the durability of plant
      disease resistance has been lacking. Here, we developed near-isogenic
      experimental lines representing all possible combinations of four QTL alleles
      from a durably resistant cultivar. These lines enabled us to evaluate the QTLs
      singly and in combination in a homogeneous genetic background. We present
      evidence that pyramiding QTL alleles, each controlling a different response to M.
      oryzae, confers strong, non-race-specific, environmentally stable resistance to
      blast disease. Our results suggest that this robust defence system provides
      durable resistance, thus avoiding an evolutionary "arms race" between a crop and
      its pathogen. 

PMID- 25586964
TI  - Anti-inflammatory activity of sappanchalcone isolated from Caesalpinia sappan L.
      in a collagen-induced arthritis mouse model.
AB  - Sappanchalcone, a bioactive flavonoid isolated from the heartwood of Caesalpinia
      sappan L. possesses anti-inflammatory effects. We studied the efficacy of
      sappanchalcone in attenuating collagen-induced arthritis (CIA) in a mouse model
      of rheumatoid arthritis. Sappanchalcone was purified to homogeneity from the
      chloroform fraction of the methanolic extract of C. sappan, and identified using
      mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. CIA-induced
      male DBA/1J mice were divided into control, sappanchalcone-treated, and
      methotrexate-treated groups (n = 10 per group). Paw swelling, arthritis severity,
      radiographic and histomorphometric changes were assessed to measure the
      protective role of sappanchalcone against chronic disease progression.
      Sappanchalcone administration significantly reduced clinical arthritis and
      inflammatory edema in paws. Bone mineral density and trabecular structure were
      maintained in CIA mice administered sappanchalcone. The levels of pro
      inflammatory cytokines (TNF-alpha, IL-6, and 1L-1beta) were significantly lower
      in the serum of sappanchalcone-treated mice as compared with the control group.
      Our results suggest that sappanchalcone could be used as an anti-inflammatory and
      bone-protective agent during the treatment of rheumatoid arthritis.

PMID- 25586967
TI  - Size dependence of phase transitions in aerosol nanoparticles.
AB  - Phase transitions of nanoparticles are of fundamental importance in atmospheric
      sciences, but current understanding is insufficient to explain observations at
      the nano-scale. In particular, discrepancies exist between observations and model
      predictions of deliquescence and efflorescence transitions and the hygroscopic
      growth of salt nanoparticles. Here we show that these discrepancies can be
      resolved by consideration of particle size effects with consistent thermodynamic
      data. We present a new method for the determination of water and solute
      activities and interfacial energies in highly supersaturated aqueous solution
      droplets (Differential Kohler Analysis). Our analysis reveals that particle size
      can strongly alter the characteristic concentration of phase separation in mixed
      systems, resembling the influence of temperature. Owing to similar effects,
      atmospheric secondary organic aerosol particles at room temperature are expected
      to be always liquid at diameters below ~20 nm. We thus propose and demonstrate
      that particle size should be included as an additional dimension in the
      equilibrium phase diagram of aerosol nanoparticles.

PMID- 25586969
TI  - Clinical Obesity - a new journal for a new clinical era.

PMID- 25586966
TI  - The alveolar ridge splitting/expansion technique: a systematic review.
AB  - PURPOSE: The aim of this systematic review was to evaluate clinical, radiological
      and histological outcomes of the alveolar ridge splitting/expansion technique
      (ARST) with or without GBR. MATERIALS AND METHODS: A screening of two databases
      MEDLINE (PubMed) and EMBASE (OVID) and hand search of articles were performed.
      Human and animal studies reporting on dental implants placed with simultaneous
      ARST up to May 31st 2014 were considered. Quality assessment of selected full
      text articles was performed according to the ARRIVE guidelines and the Cochrane
      collaboration's tool to assess risk of bias. RESULTS: Overall, 18 human and six
      animal studies (risk of bias: high/unclear) were included in this review. No
      randomized controlled trials were found. Due to the heterogeneity of study
      designs, definitions of success criteria, outcome variables, observation times
      and surgical procedures, no meta-analysis was performed. Reported survival (18
      studies) and success (nine studies) rates ranged from 91.7 to 100% and 88.2 to
      100%, respectively, with a mean follow-up of 1-10 years. Crestal bone level
      changes (?CBL) in some studies indicate slightly higher bone loss before and
      after loading. Histologic and histomorphometric data from six animal studies
      confirm the crestal bone loss, particularly at buccal sites. CONCLUSIONS: Within
      the limitations of this review, ARST seems to be a well-functioning one-stage
      alternative to extended two-stage horizontal grafting procedures. Data indicate
      that during healing and first year of loading, increased ?CBL particularly at
      buccal sites must be anticipated. Additional horizontal GBR can help to preserve
      buccal bone height and width.

PMID- 25586968
TI  - Construction of a high-mannose-type glycan library by a renewed top-down chemo
      enzymatic approach.
AB  - A comprehensive method for the construction of a high-mannose-type glycan library
      by systematic chemo-enzymatic trimming of a single Man9-based precursor was
      developed. It consists of the chemical synthesis of a non-natural
      tridecasaccharide precursor, the orthogonal demasking of the non-reducing ends,
      and trimming by glycosidases, which enabled a comprehensive synthesis of high
      mannose-type glycans in their mono- or non-glucosylated forms. It employed
      glucose, isopropylidene, and N-acetylglucosamine groups for blocking the A-, B-,
      and C-arms, respectively. After systematic trimming of the precursor, thirty
      seven high-mannose-type glycans were obtained. The power of the methodology was
      demonstrated by the enzymatic activity of human recombinant N
      acetylglucosaminyltransferase-I toward M7-M3 glycans, clarifying the substrate
      specificity in the context of high-mannose-type glycans. 

PMID- 25586965
TI  - Impairment of chaperone-mediated autophagy leads to selective lysosomal
      degradation defects in the lysosomal storage disease cystinosis.
AB  - Metabolite accumulation in lysosomal storage disorders (LSDs) results in impaired
      cell function and multi-systemic disease. Although substrate reduction and
      lysosomal overload-decreasing therapies can ameliorate disease progression, the
      significance of lysosomal overload-independent mechanisms in the development of
      cellular dysfunction is unknown for most LSDs. Here, we identify a mechanism of
      impaired chaperone-mediated autophagy (CMA) in cystinosis, a LSD caused by
      defects in the cystine transporter cystinosin (CTNS) and characterized by cystine
      lysosomal accumulation. We show that, different from other LSDs, autophagosome
      number is increased, but macroautophagic flux is not impaired in cystinosis while
      mTOR activity is not affected. Conversely, the expression and localization of the
      CMA receptor LAMP2A are abnormal in CTNS-deficient cells and degradation of the
      CMA substrate GAPDH is defective in Ctns(-/-) mice. Importantly, cysteamine
      treatment, despite decreasing lysosomal overload, did not correct defective CMA
      in Ctns(-/-) mice or LAMP2A mislocalization in cystinotic cells, which was
      rescued by CTNS expression instead, suggesting that cystinosin is important for
      CMA activity. In conclusion, CMA impairment contributes to cell malfunction in
      cystinosis, highlighting the need for treatments complementary to current
      therapies that are based on decreasing lysosomal overload. 

PMID- 25586970
TI  - Review of current guidelines on adolescent bariatric surgery.
AB  - A variety of European, North American and, recently, Middle East and Australasian
      guidelines are now available for clinicians treating obese children and
      adolescents. This review aims to synthesize recommendations from recent guidance
      to provide direction to clinicians on the appropriate use of bariatric surgery in
      adolescents. A literature search for English-language guidelines endorsed by
      national governments or professional health associations or societies was
      conducted, and subject experts were consulted to identify the most recently
      released guidance. Fifteen sets of guidelines were found, released in the past 6
      years, of which nearly all suggested that bariatric surgery is indicated for
      obese paediatric patients after previous failed attempts at weight loss. Guidance
      was broadly similar in terms of the categories addressed (patient selection
      criteria, requirements of the surgical team and institution, and suggested
      preoperative and postoperative protocols), although relatively little consensus
      was evident among the criteria specified within these categories. Recommendations
      differed regarding the appropriate age and degree of obesity at which to
      intervene. Fewer guidelines addressed preoperative and postoperative care
      requirements, and of those that did the emphasis varied between familial care and
      involvement, psychological state and patient motivation, and the importance of
      long term care. There is a lack of uniformity in the guidance in this area,
      indicative of the complex nature of obesity management for younger patients.
      While guidance is necessary to inform and update clinicians, obese paediatric
      patients require individualized assessment and care. 

PMID- 25586971
TI  - Effectiveness and cost-effectiveness of paediatric bariatric surgery: a
      systematic review.
AB  - Strong evidence for successful and cost-effective obesity management strategies
      is still generally lacking, leading the medical profession to rely increasingly
      on surgical options to treat obesity in children and adolescents. We performed a
      systematic review to examine the effectiveness of surgical interventions to treat
      obese children and adolescents, and whether they are cost-effective. We searched
      PubMed, ISI Web of Science, Embase and the Cochrane Library to 6 September 2010,
      and hand-searched bibliographies. We included articles with English abstracts if
      they examined subjects <=19 years of age, reported at least one postoperative
      weight loss measure and at least 1 year of postoperative follow-up. Thirty-seven
      relevant papers on bariatric surgery effectiveness in 831 children or adolescents
      were included, spanning 36 years. Thirteen studies examined gastric banding, with
      mean body mass index (BMI) reductions ranging from 8.5 to 43 kg m(-2) . Weight
      gain was reported in one case study. Eight papers examined Roux-en-Y gastric
      bypass, with mean BMI reductions ranging from 9 to 25 kg m(-2) . Fourteen
      publications studied other forms of bariatric surgery: sleeve gastrectomies,
      vertical banded gastroplasty, biliopancreatic diversion or a combination of
      procedures. Mean BMI reductions ranged from 9 to 24 kg m(-2) . Three surgery
      related mortalities were reported, as was weight regain in several cases. The
      majority of studies reported resolution or improvement of comorbid conditions. A
      range of postoperative complications were identified across surgery types,
      including: ulcers, intestinal leakage, wound infection, anastomotic stricture,
      nutritional deficiencies, bowel obstruction, pulmonary embolism, disrupted staple
      lines, band slippage, psychological intolerance and repeated vomiting. Evidence
      on cost-effectiveness was limited to one Australian modelling project, which
      deemed laparoscopic adjustable gastric banding cost-effective for adolescents.
      Existing evidence - although based generally on underpowered, retrospective
      studies - suggests that bariatric surgery in older children results in
      significant weight loss and improvements in comorbidities and quality of life.
      However, postoperative complications, compliance and follow-up may be more
      problematic in adolescents than adults, and availability of long-term data on
      safety, effectiveness and cost-effectiveness remains largely unknown. Pending an
      improvement in the quality of available evidence, a cautious approach to child
      and adolescent bariatric surgery is warranted, and reversible techniques are
      advisable compared to approaches that permanently alter anatomy. 

PMID- 25586972
TI  - Does medically induced weight loss improve obstructive sleep apnoea in the obese:
      review of randomized trials.
AB  - Obstructive sleep apnoea is characterized by repeated periods of breathing
      cessation during sleep. Obstructive sleep apnoea is both common and
      underdiagnosed in the obese. A recent study found that as many as 86% of older
      obese type 2 diabetics had obstructive sleep apnoea. Obesity is independently
      associated with developing obstructive sleep apnoea, and the reverse may also
      occur. The prevalence of obstructive sleep apnoea is therefore expected to rise
      in the wake of the obesity epidemic. The number of partial (hypopnoea) or
      complete (apnoea) airway obstructions per hour (apnoea-hypopnoea index) is used
      to classify obstructive sleep apnoea as mild (5-14 events per hour), moderate (15
      30) or severe (>30). Severe obstructive sleep apnoea is associated with a two to
      sixfold increase in all-cause mortality; the impact of mild and moderate
      obstructive sleep apnoea is less clear. Until recently, the evidence supporting a
      beneficial effect of weight loss on obstructive sleep apnoea has been limited by
      a lack of randomized trials. In 2009, at least three randomized controlled trials
      evaluated whether medically induced weight loss improves obstructive sleep
      apnoea. The treatment effect ranged from 42% to 62% improvement, although the
      highest estimate was seen in a very short duration study (9 weeks). Patients who
      either lost 10-15 kg or more, or had severe obstructive sleep apnoea at baseline,
      benefited most from treatment. 

PMID- 25586973
TI  - Comparison of a low-energy diet and a very low-energy diet in sedentary obese
      individuals: a pragmatic randomized controlled trial.
AB  - There is no consensus on whether 'very low-energy diets' (VLED; <800 kcal d(-1) )
      cause greater weight loss in obese individuals than 'low-energy diets' (LED; 800
      1200 kcal d(-1) ). The objective was to determine whether a very low-energy
      formula diet would cause greater weight loss than a formula 810 kcal d(-1) LED in
      older sedentary individuals. This is a pragmatic randomized controlled trial.
      INCLUSION CRITERIA: obesity (body mass index [BMI] > 30); age >50 years, with
      knee osteoarthritis. Participants were randomized to VLED (420-554 kcal d(-1) )
      or LED (810 kcal d(-1) ) for 8 weeks, followed by a fixed-energy (1200 kcal d(-1)
      ) diet with food and two diet products daily for 8 weeks. In all, 192
      participants were randomized. Mean age was 63 years (standard deviation: 6), mean
      weight 103.2 kg (15.0) and BMI of 37.3 kg m(-2) (4.8) at baseline. Mean weight
      losses in VLED and LED groups were 11.4 kg (standard error: 0.5) and 10.7 kg
      (0.5) at week 8 and 13.3 kg (0.7) and 12.2 kg (0.6) at week 16. Mean differences
      between groups were 0.76 kg (95% confidence interval: -0.59 to 2.10; P = 0.27)
      and 1.08 kg (-0.66 to 2.81; P = 0.22) at 8 and 16 weeks, respectively. Loss of
      lean body mass was 2.1 kg (0.2) and 1.2 kg (0.4) (17% and 11% of the weight lost,
      respectively) at week 16 in the VLED and LED group with a mean difference of 0.85
      kg (0.01 to 1.69; P = 0.047). Significant adverse effects comparing VLED and LED,
      were bad breath: 34 (35%) vs. 21 (22%), intolerance to cold: 39 (41%) vs. 17
      (18%) and flatulence: 43 (45%) vs. 28 (29%) for VLED and LED at 8 weeks (P < 0.05
      in all cases). The VLED and LED regimens were equally successful in inducing
      weight loss. The significantly lower loss of lean tissue in the LED group
      together with more frequently reported side effects in the VLED group, favours
      the choice of low-energy diet (LED) for the treatment of obesity.

PMID- 25586975
TI  - Osteoarthritis - a role for weight management in rheumatology practice: an
      update.
AB  - Osteoarthritis (OA) and obesity are related diseases, which occur in a large
      proportion of the population. Epidemiological evidence show that weight is of
      great importance for the development of OA in the knee, and to some extent also
      in hip and finger joints. Once acquired, the OA contributes to further weight
      problems by decreasing the daily activity level. Weight loss will be beneficial
      for the knee and experimental data point at a highly significant effect on knee
      function and recent results even point at a positive effect on the cartilage of
      the knee joint. Recommending patients with a combination of knee OA and obesity
      to lose at least 5% body weight, and aim for 10% is predicted to correspond to
      26% improvement in physical function. A programme for this weight loss has been
      tested with good results applying an initial formula diet with maintenance
      therapy in groups during follow-up. 

PMID- 25586974
TI  - VLED and formula LED in the management of type 2 diabetes: defining the clinical
      need and research requirements.
AB  - It has been known for many years that substantial weight loss, achieved by
      bariatric surgery or non-surgical means can mean normalize glucose tolerance.
      Recent randomized controlled trial evidence indicates that >15 kg weight loss is
      necessary, to this and it may lead to near normalization (doubling) of life
      expectancy. Less than 5% of patients achieve this through even the best, evidence
      based medical weight management programme (Counterweight
      http://www.counterweight.org). A weight loss of >15 kg is easily achievable by 8
      weeks very low-energy diet (VLED)/LELD (Low energy Liquid-formula Diet) in
      compliant patients, with little difference between 400 and 800 kcal day(-1) , but
      weight maintenance after VLED has until recently been so poor that VLED is not,
      at present, recommended in clinical guidelines. However, mean weight loss close
      to >15 kg can be maintained 18-24 months using a variety of maintenance
      strategies. These include a structured reintroduction of foods linked to an
      education programme with behavioural strategies, intermittent VLED use and
      prescribable anti-obesity drugs (dexfenfluramine, orlistat, sibutramine). Most of
      these studies have been in non-diabetic subjects. A new 'curative' paradigm in
      type 2 diabetes mellitus management, aiming to normalize glucose tolerance and
      health risks by achieving and maintaining >15 kg loss, as soon as possible after
      diagnosis, should be highly acceptable to patients, generating many additional
      Quality Adjusted Life Years (QALYs). It is likely to be highly cost-effective by
      avoiding the current recommended, mainly palliative, model, using polypharmacy
      which provides an overall risk reduction of only 5-10%. Clinical trials are on
      going to establish the feasibility of delivering formula (LELD) and a maintenance
      programme to large numbers of patients within routine primary care. There is
      urgent need, to run similar studies in diabetic patients. New approaches to long
      term (lifelong) maintenance of weight loss and a non-diabetic state may include
      anti-obesity drugs. 

PMID- 25586976
TI  - A 60-year-old obese woman with osteoarthritis of the knee: a case-report.
AB  - A case is presented of a 60-year-old woman with concomitant obesity and knee
      osteoarthritis. The bad knees prevented the patient from exercising; however,
      with a focused dietary intervention employing food supplements for the first
      period of 8 weeks, an ordinary low-energy diet for another 8 weeks, the patient
      lost 17.3 kg; and a further weight loss was achieved during 1-year follow-up
      totalling 30.6 kg. Lean body mass only changed slightly, 96.8% of the weight loss
      being fat mass. Along with this her metabolic syndrome decreased and her gait
      improved. It is suggested that a major weight loss is the treatment of choice in
      patients with this combination of diseases. 

PMID- 25586977
TI  - Effect of a very low-energy diet on moderate and severe obstructive sleep apnoea:
      case reports.
AB  - In this article, we report two cases from our study in which we investigated the
      effect of a very low-energy diet (VLED) for 9 weeks followed by a weight
      maintenance program for a total duration of 1 year in obese men with moderate to
      severe obstructive sleep apnea. The first case was a 43-year-old man with a body
      weight of 126 kg and a body mass index (BMI) of 38.8 kg/m(2) at baseline. Over
      the 1-year treatment program he lost 26% of his initial weight and his apnea
      hypopnea index (AHI) was improved by 60%. The second case was at baseline a 54
      year-old man with a weight of 87 kg and BMI of 32.1 kg/m(2) . Over the 1-year
      treatment program he lost 10% of his initial weight and his AHI improved by 66%.
      In summary, treatment with a VLED followed by a weight maintenance program
      significantly improved obstructive sleep apnea in both cases. 

PMID- 25586979
TI  - Neuroretinitis secondary to Bartonella henselae in the emergent setting.

PMID- 25586980
TI  - Cryolipolysis for safe and effective inner thigh fat reduction.
AB  - BACKGROUND AND OBJECTIVES: While cryolipolysis initially received FDA clearance
      for fat reduction in the abdomen and flanks, there was significant interest in
      non-surgical fat reduction for other sites, such as the inner and outer thighs.
      This article reports the results of an inner thigh study which contributed to FDA
      clearance of cryolipolysis for treatment of thighs. STUDY DESIGN/MATERIAL AND
      METHODS: A flat cup vacuum applicator (CoolFit applicator, CoolSculpting System)
      was used to treat 45 subjects bilaterally in the inner thighs. Single cycle
      treatments were delivered at Cooling Intensity Factor (CIF) 41.6 for 60 minutes
      followed by 2 minutes of manual massage. Follow-up visits were conducted at 8 and
      16 weeks. Efficacy was assessed by ultrasound imaging, circumference
      measurements, and photographs. Safety was assessed by monitoring adverse events.
      Patient satisfaction was evaluated by questionnaire. RESULTS: Data is presented
      for n = 42 patients that completed the 16 week study follow-up and maintained
      their weight within 5 lbs. of baseline. Independent photo review from three
      blinded physicians found 91% correct identification of baseline clinical
      photographs. Ultrasound data indicate fat layer reduction of 2.8 mm.
      Circumferential measurements indicate mean reduction of 0.9 cm. Patient
      questionnaires reveal 93% were satisfied with the CoolSculpting procedure; 84%
      noticed visible fat reduction; 89% would recommend to a friend; and 91% were
      likely to have a second treatment. There were no device- or procedure-related
      serious adverse events. CONCLUSION: The CoolFit flat cup vacuum applicator was
      found to deliver safe and effective cryolipolysis treatment to reduce inner thigh
      fat. Completed 16-week data from 42 subjects show 2.8 mm reduction in fat
      thickness and 0.9 cm reduction in circumference. Assessment of clinical
      photographs found 91% correct identification of baseline images. The results of
      this prospective, multi-center, interventional clinical study contributed to FDA
      clearance of cryolipolysis for treatment of thighs in April 2014.

PMID- 25586978
TI  - Disruptions in follicle cell functions in the ovaries of rhesus monkeys during
      summer.
AB  - Oocytes isolated from female rhesus monkeys following standard ovarian
      stimulation protocols during the summer months displayed a reduced capacity to
      mature compared with stimulation during the normal breeding season. Because the
      gene expression profiles of oocyte-associated cumulus cells and mural granulosa
      cells (CCs and GCs) are indicative of altered oocyte quality and can provide
      insight into intrafollicular processes that may be disrupted during oogenesis, we
      performed array-based transcriptome comparisons of CCs and GCs from summer and
      normal breeding season stimulation cycles. Summer CCs and GCs both display
      deficiencies in expression of mRNAs related to cell proliferation, angiogenesis,
      and endocrine signaling, as well as reduced expression of glycogen phosphorylase.
      Additionally, CCs display deficiencies in expression of mRNAs related to stress
      response. These results provide the first insight into the specific molecular
      pathways and processes that are disrupted in the follicles of rhesus macaque
      females during the summer season. Some of the changes seen in summer GCs and CCs
      have been reported in humans and in other model mammalian species. This suggests
      that the seasonal effects seen in the rhesus monkey may help us to understand
      better the mechanisms that contribute to reduced oocyte quality and fertility in
      humans. 

PMID- 25586981
TI  - Detection of minimal residual disease in mantle cell lymphoma-establishment of
      novel eight-color flow cytometry approach.
AB  - BACKGROUND: Minimal residual disease (MRD) detection is an essential tool for
      therapy response assessment in a considerable number of hematooncologic
      disorders, including mantle cell lymphoma (MCL). Flow cytometry (FCM) ranks among
      the most effective approaches, which allows rapid sample processing and compete
      successfully with highly sensitive molecular methods like polymerase chain
      reaction. Because FCM is ordinarily applied to detect MRD in B-lineage diseases
      like chronic lymphocytic leukemia, a similar method could be used in MCL. We
      decided to test our novel eight-color FCM approach in MCL MRD detection. METHODS:
      Using an eight-color FCM protocol designed by us, the expression of 24 selected
      surface antigens in a cohort of 30 patients with newly diagnosed leukemic MCL and
      20 normal controls were compared to establish markers that can reliably
      distinguish normal B-lymphocytes from the MCL population. The sensitivity of the
      designed protocol was tested using serial dilution studies. RESULTS: Although MCL
      presents high immunophenotypic variability, the combination of
      CD20/23/5/19/200/62L/3/45 seems to be very favorable in flow cytometric MRD
      measurement. CONCLUSIONS: Our eight-color FCM protocol could easily detect MRD in
      MCL patients, and reaches a sensitivity of up to 2 * 10(-4) .

PMID- 25586982
TI  - Non-work-related use of personal mobile phones by hospital registered nurses.
AB  - BACKGROUND: Personal mobile phones and other personal communication devices
      (smartphones and tablet computers) provide users with an ever-increasing number
      and diversity of non-work-related activities while at work. In hospitals, where
      the vigilance of health care workers is essential for patient care, the potential
      distraction of these devices could be hazardous to patients. OBJECTIVE: The
      objective of this study was to determine the frequency of non-work-related use of
      personal mobile phones and other personal communication devices among hospital
      registered nurses. METHODS: In March 2014, a previously validated 30-question
      survey was emailed to the 10,978 members of the Academy of Medical Surgical
      Nurses. There were 825 respondents who met the inclusion criteria. RESULTS: The
      use of a personal mobile phone or other personal communication device while
      working (excluding meal times and breaks) was reported by 78.1% (644/825) of
      respondents. Nurses reported regularly (sometimes, often, or always) sending
      personal emails and text messages (38.6%, 318/825), reading news (25.7%,
      212/825), checking/posting on social networking sites (20.8%, 172/825), shopping
      (9.6%, 79/825), and playing games (6.5%, 54/825) while working. CONCLUSIONS: This
      study found that hospital nurses frequently use their personal mobile phones or
      other personal communication devices for non-work-related activities at work. The
      primary activity reported was to send personal emails and text messages to family
      and friends.

PMID- 25586984
TI  - Incorporating microarray assessment of HER2 status in clinical practice supports
      individualised therapy in early-stage breast cancer.
AB  - Accurate determination of human epidermal growth factor receptor-2 (HER2) status
      is essential for optimal selection of breast cancer patients for gene targeted
      therapy. The analytical performance of microarray analysis using TargetPrint for
      assessment of HER2 status was evaluated in 138 breast tumours, including 41 fresh
      and 97 formalin-fixed paraffin embedded (FFPE) specimens. Reflex testing using
      immunohistochemistry/in situ hybridization (IHC/ISH) in four discordant cases
      confirmed the TargetPrint results, achieving 100% agreement regardless of whether
      fresh tissue or FFPE specimens were used. One equivocal IHC/ISH case was
      classified as HER2-positive based on the microarray result. The proven clinical
      utility in resolving equivocal and borderline cases justifies modification of the
      testing algorithm under these circumstances, to obtain a definitive positive or
      negative test result with the use of microarrays. Determination of HER2 status
      across three assay platforms facilitated improved quality assurance and led to a
      higher level of confidence on which to base treatment decisions.

PMID- 25586983
TI  - Digital storytelling: an innovative legacy-making intervention for children with
      cancer.
AB  - BACKGROUND: This study examined the feasibility of a legacy-making intervention
      in children with cancer and the preliminary effects on outcomes related to
      quality of life. PROCEDURE: Children (N = 28) ages 7-17 years completed a
      baseline QOL questionnaire (PedsQL) at T1. After baseline, the intervention group
      (n = 15) completed a randomized intervention that guided children to answer
      questions about legacy-making and create a digital story about themselves. A
      final copy of the digital story was provided to the families. A control group (n
      = 13) received customary care. Children repeated the questionnaire at T2. Parents
      (N = 22) of children who completed the intervention completed follow-up survey
      questions regarding intervention effects. RESULTS: Feasibility was strong (78%
      participation; 1 attrition). While differences between the groups in physical,
      emotional, social, or school functioning change was not statistically
      significant, the intervention group showed slightly better emotional and school
      functioning compared to controls. Parents reported that their child's digital
      story provided emotional comfort to them (n = 11, 46%), facilitated communication
      between parents and children (n = 9, 38%), and was a coping strategy for them (n
      = 4, 17%). Parents reported that the intervention helped children express their
      feelings (n = 19, 79%), cope (n = 6, 27%), and feel better emotionally (n = 5,
      23%). CONCLUSIONS: Our intervention is feasible for children with cancer, is
      developmentally appropriate for children 7-17 years of age, and demonstrates
      promise to improve quality of life outcomes for children with cancer and their
      parents.

PMID- 25586986
TI  - Infection control: beyond the horizon.
AB  - This article will consider possible future directions for innovation and research
      in infection prevention and control, and will make the case for the importance of
      including clinical and cost-effectiveness evaluation in such research.
      Opportunities for studies in a number of broad subject areas will be considered,
      including prevention and control of existing and emerging infection hazards, the
      challenges posed by changes in the way that medical care is being delivered,
      technological developments that could be harnessed for infection prevention and
      control, how new laboratory diagnostic technologies might benefit infection
      prevention and control, cleaning and decontamination, and the infection control
      aspects of hospital design. The need for robust economic data to support the wide
      and timely implementation of evidence-based practice is emphasized. 

PMID- 25586987
TI  - Sociocognitive predictors of the intention of healthcare workers to receive the
      influenza vaccine in Belgian, Dutch and German hospital settings.
AB  - BACKGROUND: Influenza vaccination of healthcare workers (HCWs) is recommended to
      prevent the transmission of influenza to vulnerable patients. Nevertheless,
      vaccination coverage rates of HCWs in European countries have been low. AIM: To
      investigate the relative and combined strength of sociocognitive variables, from
      past research, theory and a qualitative study, in explaining the motivation of
      HCWs to receive the influenza vaccine. METHODS: An anonymous, online
      questionnaire was distributed among HCWs in hospital settings in Belgium, Germany
      and the Netherlands between February and April 2013. FINDINGS: Attitude and past
      vaccination uptake explained a considerable amount of variance in the intention
      of HCWs to receive the influenza vaccine. Moreover, low perceived social norms,
      omission bias, low moral norms, being older, having no patient contact, and being
      Belgian or Dutch (compared with German) increased the probability of having no
      intention to receive the influenza vaccine compared with being undecided about
      vaccination. High intention to receive the influenza vaccine was shown to be more
      likely than being undecided about vaccination when HCWs had high perceived
      susceptibility of contracting influenza, low naturalistic views, and lower
      motivation to receive the vaccine solely for self-protection. CONCLUSION: Country
      specific interventions and a focus on different sociocognitive variables
      depending on the intention/lack of intention of HCWs to receive the influenza
      vaccine may be beneficial to promote vaccination uptake.

PMID- 25586988
TI  - Comparison of different hand-drying methods: the potential for airborne microbe
      dispersal and contamination.
AB  - Efficient washing and drying of hands is important in prevention of the transfer
      of micro-organisms. However, knowledge surrounding the potential for microbial
      contamination according to hand-drying methods is limited. This study assessed
      the potential for airborne microbe dispersal during hand drying by four methods
      (paper towels, roller towel, warm air and jet air dryer) using three different
      models. The jet air dryer dispersed liquid from users' hands further and over a
      greater range (up to 1.5m) than the other drying methods (up to 0.75 m),
      demonstrating the differing potential risks for airborne microbe dissemination,
      particularly if handwashing is suboptimal.

PMID- 25586989
TI  - Letter to the editor: An intriguing relationship between lipid droplets,
      cholesterol-binding protein CD133 and Wnt/beta-catenin signaling pathway in
      carcinogenesis.

PMID- 25586990
TI  - Successful rapid desensitization to the antibody-drug conjugate brentuximab
      vedotin in a patient with refractory Hodgkin lymphoma.

PMID- 25586991
TI  - TRIB2 as a biomarker for diagnosis and progression of melanoma.
AB  - Malignant melanoma is the most deadly form of skin cancer. There is a critical
      need to identify the patients that could be successfully treated by surgery alone
      and those that require adjuvant treatment. In this study, we demonstrate that the
      expression of tribbles2 (TRIB2) strongly correlates with both the presence and
      progression of melanocyte-derived malignancies. We examined the expression of
      TRIB2 in addition to 12 previously described melanoma biomarkers across three
      independent full genome microarray studies. TRIB2 expression was consistently and
      significantly increased in benign nevi and melanoma, and was highest in samples
      from patients with metastatic melanoma. The expression profiles for the 12
      biomarkers were poorly conserved throughout these studies with only TYR, S100B
      and SPP1 showing consistently elevated expression in metastatic melanoma versus
      normal skin. Strikingly we confirmed these findings in 20 freshly obtained
      primary melanoma tissue samples from metastatic lesions where the expression of
      these biomarkers were evaluated revealing that TRIB2 expression correlated with
      disease stage and clinical prognosis. Our results suggest that TRIB2 is a
      meaningful biomarker reflecting diagnosis and progression of melanoma, as well as
      predicting clinical response to chemotherapy. 

PMID- 25586994
TI  - Response to: Letter to the editor by C Benn, A Fisker and P Aaby.

PMID- 25586993
TI  - Brain-derived neurotrophic factor deficiency restricts proliferation of
      oligodendrocyte progenitors following cuprizone-induced demyelination.
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family
      of growth factors that through its neurotrophic tyrosine kinase, receptor, type 2
      (TrkB) receptor, increases 5-bromo-2-deoxyuridine incorporation in
      oligodendrocyte progenitor cells (OPCs) in culture. Roles in vivo are less well
      understood; however, increases in numbers of OPCs are restricted in BDNF+/- mice
      following cuprizone-elicited demyelination. Here, we investigate whether these
      blunted increases in OPCs are associated with changes in proliferation. BDNF+/+
      and BDNF+/- mice were fed cuprizone-containing or control feed. To assess effects
      on OPC numbers, platelet-derived growth factor receptor alpha (PDGFRalpha)+ or
      NG2+ cells were counted. To monitor DNA synthesis, 5-ethynyl-2'-deoxyuridine
      (EdU) was injected intraperitoneally and colocalized with PDGFRalpha+ cells.
      Alternatively, proliferating cell nuclear antigen (PCNA) was colocalized with
      PDGFRalpha or NG2. Labeling indices were determined in the BDNF+/+ and BDNF+/-
      animals. After 4 or 5 weeks of control feed, BDNF+/- mice exhibit similar numbers
      of OPCs compared with BDNF+/+ animals. The labeling indices for EdU and PCNA also
      were not significantly different, suggesting that neither the DNA synthesis phase
      (S phase) nor the proliferative pool size was different between genotypes. In
      contrast, when mice were challenged by cuprizone for 4 or 5 weeks, increases in
      OPCs observed in BDNF+/+ mice were reduced in the BDNF+/- mice. This difference
      in elevations in cell number was accompanied by decreases in EdU labeling and
      PCNA labeling without changes in cell death, indicating a reduction in the DNA
      synthesis and the proliferative pool. Therefore, levels of BDNF influence the
      proliferation of OPCs resulting from a demyelinating lesion. 

PMID- 25586995
TI  - Effect on child cognitive function of increasing household expenditure in
      Indonesia: application of a marginal structural model and simulation of a cash
      transfer programme.
AB  - BACKGROUND: Parental investments in children are an important determinant of
      human capability formation. We investigated the causal effect of household
      expenditure on Indonesian children's cognitive function between 2000 and 2007. We
      also investigated the effect of change in mean cognitive function from a
      simulation of a hypothetical cash transfer intervention. METHODS: A longitudinal
      analysis using data from the Indonesian Family Life Survey (IFLS) was conducted
      including 6136 children aged 7 to 14 years in 2000 and still alive in 2007. We
      used the inverse probability of treatment weighting of a marginal structural
      model to estimate the causal effect of household expenditure on children's
      cognitive function. RESULTS: Cumulative household expenditure was positively
      associated with cognitive function z-score. From the marginal structural model, a
      74534 rupiah/month (about US$9) increase in household expenditure resulted in a
      0.03 increase in cognitive function z-score [beta=0.32, 95% confidence interval
      (CI) 0.30-0.35] Based on our simulations, among children in the poorest
      households in 2000 an additional ~ US$6-10 of cash transfer resulted in a 0.01
      unit increase in cognitive function z-score, equivalent to about 6% increase from
      the mean z-score prior to cash transfer. In contrast, children in the poorest
      household in 2007 did not benefit from an additional ~ US$10 cash transfer. We
      found no overall effect of cash transfers at the total population level.
      CONCLUSIONS: Greater household expenditure had a small causal effect on
      children's cognitive function. Although cash transfer interventions had a
      positive effect for poor children, this effect was quite small. Multi-faceted
      interventions that combine nutrition, cash transfer, improved living conditions
      and women's education are required to benefit children's cognitive development in
      Indonesia.

PMID- 25586999
TI  - Description of an Automated Method for Urea Nitrogen Determination in
      Bronchoalveolar Lavage Fluid (BALF) of Neonates and Infants.
AB  - Bronchoalveolar lavage (BAL) partially recovers both the instilled saline and the
      alveolar fluid, so-called epithelial lining fluid (ELF), but a correction for the
      dilution due to the BAL technique itself is needed to know the amount of
      recovered ELF. In this regard, urea nitrogen may be useful and has been proposed
      to calculate ELF. The aim of the present study was to develop and validate a new
      method to measure urea nitrogen in BAL fluid (BALF). We used 19 BALF samples
      obtained from neonates and infants with different respiratory conditions. The
      urea nitrogen assay was carried out on Cobas c311 analyzer (Roche Diagnostics). A
      validation study shows that the method is perfectly linear (R(2) = 0.999),
      sensitive (limit of detection = 0.055 mg/dL; limit of quantification = 0.16
      mg/dL), repeatable (low = 0.15 +/- 0.02, 13.3%; high = 1.80 +/- 0.02, 1.1%),
      reproducible (low = 0.14 +/- 0.02, 14.2 %; high = 1.76 +/- 0.04, 2.2 %) with
      accuracy ranging between 93-96%. Our results support the robustness of validated
      procedure since the described method appears simple, precise, rapid, and suitable
      for routine analysis. Thus, it may be used to correct concentration of various
      noncellular BAL components and calculate their ELF amounts in neonates and
      infants. 

PMID- 25587000
TI  - An Overview on Prenatal Screening for Chromosomal Aberrations.
AB  - This article is a review of current and emerging methods used for prenatal
      detection of chromosomal aneuploidies. Chromosomal anomalies in the developing
      fetus can occur in any pregnancy and lead to death prior to or shortly after
      birth or to costly lifelong disabilities. Early detection of fetal chromosomal
      aneuploidies, an atypical number of certain chromosomes, can help parents
      evaluate their pregnancy options. Current diagnostic methods include maternal
      serum sampling or nuchal translucency testing, which are minimally invasive
      diagnostics, but lack sensitivity and specificity. The gold standard,
      karyotyping, requires amniocentesis or chorionic villus sampling, which are
      highly invasive and can cause abortions. In addition, many of these methods have
      long turnaround times, which can cause anxiety in mothers. Next-generation
      sequencing of fetal DNA in maternal blood enables minimally invasive, sensitive,
      and reasonably rapid analysis of fetal chromosomal anomalies and can be of
      clinical utility to parents. This review covers traditional methods and next
      generation sequencing techniques for diagnosing aneuploidies in terms of clinical
      utility, technological characteristics, and market potential. 

PMID- 25587001
TI  - The clinical pattern of diabetes Insipidus in a large university hospital in the
      Middle East.
AB  - Diabetes insipidus is a rare but serious endocrine disorder. Paediatric patients
      were evaluated for polyuria at King Khalid University Hospital, Riyadh, Saudi
      Arabia, over a decade (2000-13). Relevant clinical examination and/or a triad of
      high serum osmolality, hypernatremia and low urine osmolality due to increased
      urine output confirmed the diagnosis. Water deprivation test was required in some
      cases with non-classic presentations. Appropriate brain imaging was performed
      whenever central diabetes insipidus (CDI) was suspected. Twenty-eight patients,
      15 males (53.6%) and 13 females (46.4%), aged 0-17 years (mean: 6 years) were
      included. The calculated period prevalence was 7 in 10,000. In our cohort, 60.7%
      (17 of 28 patients) had CDI, 21.4% (6 of 28) were diagnosed with nephrogenic
      diabetes insipidus (NDI) and 17.9% (5 of 30) had psychogenic polydipsia. CDI was
      due to variable aetiology. Though CDI was the commonest, NDI was not a rare
      encounter in our community, possibly because of high consanguineous marriages.

PMID- 25586998
TI  - TEER measurement techniques for in vitro barrier model systems.
AB  - Transepithelial/transendothelial electrical resistance (TEER) is a widely
      accepted quantitative technique to measure the integrity of tight junction
      dynamics in cell culture models of endothelial and epithelial monolayers. TEER
      values are strong indicators of the integrity of the cellular barriers before
      they are evaluated for transport of drugs or chemicals. TEER measurements can be
      performed in real time without cell damage and generally are based on measuring
      ohmic resistance or measuring impedance across a wide spectrum of frequencies.
      The measurements for various cell types have been reported with commercially
      available measurement systems and also with custom-built microfluidic
      implementations. Some of the barrier models that have been widely characterized
      using TEER include the blood-brain barrier (BBB), gastrointestinal (GI) tract,
      and pulmonary models. Variations in these values can arise due to factors such as
      temperature, medium formulation, and passage number of cells. The aim of this
      article is to review the different TEER measurement techniques and analyze their
      strengths and weaknesses, determine the significance of TEER in drug toxicity
      studies, examine the various in vitro models and microfluidic organs-on-chips
      implementations using TEER measurements in some widely studied barrier models
      (BBB, GI tract, and pulmonary), and discuss the various factors that can affect
      TEER measurements. 

PMID- 25586992
TI  - Inherited variants in the inner centromere protein (INCENP) gene of the
      chromosomal passenger complex contribute to the susceptibility of ER-negative
      breast cancer.
AB  - The chromosomal passenger complex (CPC) plays a pivotal role in the regulation of
      cell division. Therefore, inherited CPC variability could influence tumor
      development. The present candidate gene approach investigates the relationship
      between single nucleotide polymorphisms (SNPs) in genes encoding key CPC
      components and breast cancer risk. Fifteen SNPs in four CPC genes (INCENP, AURKB,
      BIRC5 and CDCA8) were genotyped in 88 911 European women from 39 case-control
      studies of the Breast Cancer Association Consortium. Possible associations were
      investigated in fixed-effects meta-analyses. The synonymous SNP rs1675126 in exon
      7 of INCENP was associated with overall breast cancer risk [per A allele odds
      ratio (OR) 0.95, 95% confidence interval (CI) 0.92-0.98, P = 0.007] and
      particularly with estrogen receptor (ER)-negative breast tumors (per A allele OR
      0.89, 95% CI 0.83-0.95, P = 0.0005). SNPs not directly genotyped were imputed
      based on 1000 Genomes. The SNPs rs1047739 in the 3' untranslated region and
      rs144045115 downstream of INCENP showed the strongest association signals for
      overall (per T allele OR 1.03, 95% CI 1.00-1.06, P = 0.0009) and ER-negative
      breast cancer risk (per A allele OR 1.06, 95% CI 1.02-1.10, P = 0.0002). Two
      genotyped SNPs in BIRC5 were associated with familial breast cancer risk (top SNP
      rs2071214: per G allele OR 1.12, 95% CI 1.04-1.21, P = 0.002). The data suggest
      that INCENP in the CPC pathway contributes to ER-negative breast cancer
      susceptibility in the European population. In spite of a modest contribution of
      CPC-inherited variants to the total burden of sporadic and familial breast
      cancer, their potential as novel targets for breast cancer treatment should be
      further investigated. 

PMID- 25587004
TI  - Efficacy of jollab in the treatment of depression in dyspeptic patients: a
      randomized double-blind controlled trial.
AB  - The current study aimed to evaluate the efficacy of jollab, a well-known beverage
      from traditional Persian medicine in the treatment of depression among patients
      suffering from functional dyspepsia. In a randomized, double-blind, placebo
      controlled trial, a pair of 80 patients were enrolled in 2 parallel groups as
      Jollab and placebo. The Beck Depression Inventory-II questionnaire was used for
      the assessment. At all, 133 patients enrolling in the treatment and placebo
      groups ended the protocol. According to the outcomes, changes in scores between
      the 2 groups were statistically significant at the end of trial (P <= .001).
      Taken as a whole, treatment group was significantly more effective than the
      placebo. Focusing on nutritional and pharmaceutical properties, jollab may be
      introduced not only as a medication for depression and allied ailment but also a
      pleasant daily drink. 

PMID- 25587003
TI  - MET1 is a thylakoid-associated TPR protein involved in photosystem II
      supercomplex formation and repair in Arabidopsis.
AB  - Photosystem II (PSII) requires constant disassembly and reassembly to accommodate
      replacement of the D1 protein. Here, we characterize Arabidopsis thaliana MET1, a
      PSII assembly factor with PDZ and TPR domains. The maize (Zea mays) MET1 homolog
      is enriched in mesophyll chloroplasts compared with bundle sheath chloroplasts,
      and MET1 mRNA and protein levels increase during leaf development concomitant
      with the thylakoid machinery. MET1 is conserved in C3 and C4 plants and green
      algae but is not found in prokaryotes. Arabidopsis MET1 is a peripheral thylakoid
      protein enriched in stroma lamellae and is also present in grana. Split-ubiquitin
      assays and coimmunoprecipitations showed interaction of MET1 with stromal loops
      of PSII core components CP43 and CP47. From native gels, we inferred that MET1
      associates with PSII subcomplexes formed during the PSII repair cycle. When grown
      under fluctuating light intensities, the Arabidopsis MET1 null mutant (met1)
      showed conditional reduced growth, near complete blockage in PSII supercomplex
      formation, and concomitant increase of unassembled CP43. Growth of met1 in high
      light resulted in loss of PSII supercomplexes and accelerated D1 degradation. We
      propose that MET1 functions as a CP43/CP47 chaperone on the stromal side of the
      membrane during PSII assembly and repair. This function is consistent with the
      observed differential MET1 accumulation across dimorphic maize chloroplasts. 

PMID- 25587002
TI  - Transposition of a rice Mutator-like element in the yeast Saccharomyces
      cerevisiae.
AB  - Mutator-like transposable elements (MULEs) are widespread in plants and are well
      known for their high transposition activity as well as their ability to duplicate
      and amplify host gene fragments. Despite their abundance and importance, few
      active MULEs have been identified. In this study, we demonstrated that a rice
      (Oryza sativa) MULE, Os3378, is capable of excising and reinserting in yeast
      (Saccharomyces cerevisiae), suggesting that yeast harbors all the host factors
      for the transposition of MULEs. The transposition activity induced by the wild
      type transposase is low but can be altered by modification of the transposase
      sequence, including deletion, fusion, and substitution. Particularly, fusion of a
      fluorescent protein to the transposase enhanced the transposition activity,
      representing another approach to manipulate transposases. Moreover, we identified
      a critical region in the transposase where the net charge of the amino acids
      seems to be important for activity. Finally, transposition efficiency is also
      influenced by the element and its flanking sequences (i.e., small elements are
      more competent than their large counterparts). Perfect target site duplication is
      favorable, but not required, for precise excision. In addition to the potential
      application in functional genomics, this study provides the foundation for
      further studies of the transposition mechanism of MULEs. 

PMID- 25587005
TI  - Severe maternal morbidity associated with maternal birthplace in three high
      immigration settings.
AB  - BACKGROUND: Maternal mortality and morbidity vary substantially worldwide. It is
      unknown if these geographic differences translate into disparities in severe
      maternal morbidity among immigrants from various world regions. We assessed
      disparities in severe maternal morbidity between immigrant women from various
      world regions giving birth in three high-immigration countries. METHODS: We used
      population-based delivery data from Victoria; Australia and Ontario, Canada and
      national data from Denmark, in the most recent 10-year period ending in 2010
      available to each participating centre. Each centre provided aggregate data
      according to standardized definitions of the outcome, maternal regions of birth
      and covariates for pooled analyses. We used random effects and stratified
      logistic regression to obtain odds ratios (ORs) with 95% confidence intervals
      (95% CIs), adjusted for maternal age, parity and comparability scores. RESULTS:
      We retrieved 2,322,907 deliveries in all three receiving countries, of which
      479,986 (21%) were to immigrant women. Compared with non-immigrants, only Sub
      Saharan African women were consistently at higher risk of severe maternal
      morbidity in all three receiving countries (pooled adjusted OR: 1.67; 95% CI:
      1.43, 1.95). In contrast, both Western and Eastern European immigrants had lower
      odds (OR: 0.82; 95% CI: 0.70, 0.96 and OR: 0.64; 95% CI: 0.49, 0.83,
      respectively). The most common diagnosis was severe pre-eclampsia followed by
      uterine rupture, which was more common among Sub-Saharan Africans in all three
      settings. CONCLUSIONS: Immigrant women from Sub-Saharan Africa have higher rates
      of severe maternal morbidity. Other immigrant groups had similar or lower rates
      than the majority locally born populations.

PMID- 25587006
TI  - A case of intestinal duplication.

PMID- 25587007
TI  - Nutrition rehabilitation in the intensive care unit.
AB  - The maintenance of homeostasis after severe injury requires the restoration of
      the physiological regulation of food intake. A wide array of functional
      alterations can hinder the intake of adequate amounts of nutrients to support the
      recovery from critical illness. These alterations encompass changes in the
      preprandial phase, reflected by a loss of appetite; changes in the prandial
      phase, yielding swallowing disorders; and changes in the postprandial phase,
      including impairments of gastric emptying, gut motility, and satiety. This
      tutorial aims to review these often overlooked features and to suggest
      recommendations for the nutrition rehabilitation of the critically ill. 

PMID- 25587008
TI  - One-Step Insertion of Low-Profile Gastrostomy in Pediatric Patients vs Pull
      Percutaneous Endoscopic Gastrostomy: Retrospective Analysis of Outcomes.
AB  - BACKGROUND: Standard care for initiation of enteral feeding in children has been
      pull percutaneous endoscopic gastrostomy (pull-PEG). As an alternative to pull
      PEG, a 1-step endoscopic procedure for inserting a low-profile gastrostomy tube
      "button" has been developed that allows initial placement of a balloon-retained
      device. This report presents outcomes of metrics used to compare button placement
      with pull-PEG in a pediatric population. METHODS: Data were generated from
      procedural experiences of surgeons on pediatric patients (n = 374) with a variety
      of clinical indications for gastrostomy. Study population ages ranged from 6 days
      to 16 years, while weights were from 2-84 kg. RESULTS: The button was
      successfully placed by the 1-step procedure in 98% of the respective study
      population, and median procedural times were 20 and 15 minutes for button and
      pull-PEG placements, respectively. Median times to first feeds were equivalent
      for the 1-step procedure and pull-PEG (6 hours), while times to first nutrition
      feeds were 12.5 and 10 hours, respectively. Stoma site complications within each
      study group were similar. Healthy stoma proportions were 65.2% and 73.2% in the 1
      step procedure and pull-PEG groups, respectively, at first follow-up.
      CONCLUSIONS: Similar study outcomes between the 1-step procedure and pull-PEG
      groups suggest that the former is a feasible alternative to pull-PEG for initial
      tube placement in children. The 1-step method involves a single procedure and
      reduces patient exposure to anesthesia, operating room time, and the potential
      for complications compared with a pull-PEG requirement for multiple procedures.

PMID- 25587009
TI  - Taurine Concentrations Decrease in Critically Ill Patients With Shock Given
      Enteral Nutrition.
AB  - BACKGROUND: Nutrition studies in the intensive care unit (ICU) have shown that
      adequate enteral nutrition (EN) support has clinical benefits. However, the
      course of amino acid concentrations in plasma has never been investigated in
      patients admitted with shock receiving EN. We hypothesized that plasma
      concentrations, when deficit, increase during EN and that persistent deficiency
      is associated with poor outcome. METHODS: In 33 septic or cardiogenic shock
      patients receiving EN, plasma amino acid concentrations were measured during 5
      days. Changes in amino acid concentrations, correlations with clinical outcome
      variables, and regression analyses were studied. RESULTS: On ICU admission,
      several plasma concentrations were deficient. Plasma concentrations of almost all
      amino acids increased. In contrast, taurine decreased by >50%, from 47.6 umol/L
      on admission to 20.0 umol/L at day 1, and remained low at day 5. Taurine
      (admission) correlated with time on mechanical ventilation (R = -0.42, P = .015).
      Taurine decrease within 24 hours correlated with Acute Physiology and Chronic
      Health Evaluation II predicted mortality (R = 0.43, P = .017) and Sequential
      Organ Failure Assessment score (R = 0.36, P = .05). Regression analyses confirmed
      correlations. CONCLUSIONS: Several amino acids were deficient in plasma on ICU
      admission but increased during EN. Taurine concentrations declined and were
      associated with longer periods of mechanical ventilation and ICU support. Fast
      taurine decline correlated with severity of organ failure. These findings support
      the role of taurine during ischemia, reperfusion, and inflammation. Taurine may
      be an essential candidate to enrich nutrition support for critically ill
      patients, although more research is required.

PMID- 25587010
TI  - Genomic avenue to avian colisepticemia.
AB  - Here we present an extensive genomic and genetic analysis of Escherichia coli
      strains of serotype O78 that represent the major cause of avian colisepticemia,
      an invasive infection caused by avian pathogenic Escherichia coli (APEC) strains.
      It is associated with high mortality and morbidity, resulting in significant
      economic consequences for the poultry industry. To understand the genetic basis
      of the virulence of avian septicemic E. coli, we sequenced the entire genome of a
      clinical isolate of serotype O78-O78:H19 ST88 isolate 789 (O78-9)-and compared it
      with three publicly available APEC O78 sequences and one complete genome of APEC
      serotype O1 strain. Although there was a large variability in genome content
      between the APEC strains, several genes were conserved, which are potentially
      critical for colisepticemia. Some of these genes are present in multiple copies
      per genome or code for gene products with overlapping function, signifying their
      importance. A systematic deletion of each of these virulence-related genes
      identified three systems that are conserved in all septicemic strains examined
      and are critical for serum survival, a prerequisite for septicemia. These are the
      plasmid-encoded protein, the defective ETT2 (E. coli type 3 secretion system 2)
      type 3 secretion system ETT2sepsis, and iron uptake systems. Strain O78-9 is the
      only APEC O78 strain that also carried the regulon coding for yersiniabactin, the
      iron binding system of the Yersinia high-pathogenicity island. Interestingly,
      this system is the only one that cannot be complemented by other iron uptake
      systems under iron limitation and in serum. IMPORTANCE: Avian colisepticemia is a
      severe systemic disease of birds causing high morbidity and mortality and
      resulting in severe economic losses. The bacteria associated with avian
      colisepticemia are highly antibiotic resistant, making antibiotic treatment
      ineffective, and there is no effective vaccine due to the multitude of serotypes
      involved. To understand the disease and work out strategies to combat it, we
      performed an extensive genomic and genetic analysis of Escherichia coli strains
      of serotype O78, the major cause of the disease. We identified several potential
      virulence factors, conserved in all the colisepticemic strains examined, and
      determined their contribution to growth in serum, an absolute requirement for
      septicemia. These findings raise the possibility that specific vaccines or drugs
      can be developed against these critical virulence factors to help combat this
      economically important disease.

PMID- 25587011
TI  - An intracellular nanotrap redirects proteins and organelles in live bacteria.
AB  - Owing to their small size and enhanced stability, nanobodies derived from
      camelids have previously been used for the construction of intracellular
      "nanotraps," which enable redirection and manipulation of green fluorescent
      protein (GFP)-tagged targets within living plant and animal cells. By taking
      advantage of intracellular compartmentalization in the magnetic bacterium
      Magnetospirillum gryphiswaldense, we demonstrate that proteins and even entire
      organelles can be retargeted also within prokaryotic cells by versatile nanotrap
      technology. Expression of multivalent GFP-binding nanobodies on magnetosomes
      ectopically recruited the chemotaxis protein CheW1-GFP from polar chemoreceptor
      clusters to the midcell, resulting in a gradual knockdown of aerotaxis.
      Conversely, entire magnetosome chains could be redirected from the midcell and
      tethered to one of the cell poles. Similar approaches could potentially be used
      for building synthetic cellular structures and targeted protein knockdowns in
      other bacteria. IMPORTANCE: Intrabodies are commonly used in eukaryotic systems
      for intracellular analysis and manipulation of proteins within distinct
      subcellular compartments. In particular, so-called nanobodies have great
      potential for synthetic biology approaches because they can be expressed easily
      in heterologous hosts and actively interact with intracellular targets, for
      instance, by the construction of intracellular "nanotraps" in living animal and
      plant cells. Although prokaryotic cells also exhibit a considerable degree of
      intracellular organization, there are few tools available equivalent to the well
      established methods used in eukaryotes. Here, we demonstrate the ectopic
      retargeting and depletion of polar membrane proteins and entire organelles to
      distinct compartments in a magnetotactic bacterium, resulting in a gradual
      knockdown of magneto-aerotaxis. This intracellular nanotrap approach has the
      potential to be applied in other bacteria for building synthetic cellular
      structures, manipulating protein function, and creating gradual targeted
      knockdowns. Our findings provide a proof of principle for the universal use of
      fluorescently tagged proteins as targets for nanotraps to fulfill these tasks.

PMID- 25587012
TI  - Comparative genomics suggests primary homothallism of Pneumocystis species.
AB  - Pneumocystis species are fungal parasites of mammal lungs showing host
      specificity. Pneumocystis jirovecii colonizes humans and causes severe pneumonia
      in immunosuppressed individuals. In the absence of in vitro cultures, the life
      cycle of these fungi remains poorly known. Sexual reproduction probably occurs,
      but the system of this process and the mating type (MAT) genes involved are not
      characterized. In the present study, we used comparative genomics to investigate
      the issue in P. jirovecii and Pneumocystis carinii, the species infecting rats,
      as well as in their relative Taphrina deformans. We searched sex-related genes
      using 103 sequences from the relative Schizosaccharomyces pombe as queries. Genes
      homologous to several sex-related role categories were identified in all species
      investigated, further supporting sexuality in these organisms. Extensive in
      silico searches identified only three putative MAT genes in each species
      investigated (matMc, matMi, and matPi). In P. jirovecii, these genes clustered on
      the same contig, proving their contiguity in the genome. This organization seems
      compatible neither with heterothallism, because two different MAT loci on
      separate DNA molecules would have been detected, nor with secondary homothallism,
      because the latter involves generally more MAT genes. Consistently, we did not
      detect cis-acting sequences for mating type switching in secondary homothallism,
      and PCR revealed identical MAT genes in P. jirovecii isolates from six patients.
      A strong synteny of the genomic region surrounding the putative MAT genes exists
      between the two Pneumocystis species. Our results suggest the hypothesis that
      primary homothallism is the system of reproduction of Pneumocystis species and T.
      deformans. IMPORTANCE: Sexual reproduction among fungi can involve a single
      partner (homothallism) or two compatible partners (heterothallism). We
      investigated the issue in three pathogenic fungal relatives: Pneumocystis
      jirovecii, which causes severe pneumonia in immunocompromised humans;
      Pneumocystis carinii, which infects rats; and the plant pathogen Taphrina
      deformans. The nature, the number, and the organization within the genome of the
      genes involved in sexual reproduction were determined. The three species appeared
      to harbor a single genomic region gathering only three genes involved in sexual
      differentiation, an organization which is compatible with sexual reproduction
      involving a single partner. These findings illuminate the strategy adopted by
      fungal pathogens to infect their hosts.

PMID- 25587013
TI  - Reversible antibiotic tolerance induced in Staphylococcus aureus by concurrent
      drug exposure.
AB  - Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to
      increasing use of the glycopeptide antibiotic vancomycin as a life-saving
      treatment for major S. aureus infections. Coinfection by an unrelated bacterial
      species may necessitate concurrent treatment with a second antibiotic that
      targets the coinfecting pathogen. While investigating factors that affect
      bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus
      to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide
      antimicrobial employed to treat infections by Gram-negative pathogens. We show
      that colistin-induced vancomycin tolerance persists only as long as the inducer
      is present and is accompanied by gene expression changes similar to those
      resulting from mutations that produce stably inherited reduction of vancomycin
      sensitivity (vancomycin-intermediate S. aureus [VISA] strains). As colistin
      induced vancomycin tolerance is reversible, it may not be detected by routine
      sensitivity testing and may be responsible for treatment failure at vancomycin
      doses expected to be clinically effective based on such routine testing.
      IMPORTANCE: Commonly, antibiotic resistance is associated with permanent genetic
      changes, such as point mutations or acquisition of resistance genes. We show that
      phenotypic resistance can arise where changes in gene expression result in
      tolerance to an antibiotic without any accompanying genetic changes.
      Specifically, methicillin-resistant Staphylococcus aureus (MRSA) behaves like
      vancomycin-intermediate S. aureus (VISA) upon exposure to colistin, which is
      currently used against infections by Gram-negative bacteria. Vancomycin is a last
      resort drug for treatment of serious S. aureus infections, and VISA is associated
      with poor clinical prognosis. Phenotypic and reversible resistance will not be
      revealed by standard susceptibility testing and may underlie treatment failure.

PMID- 25587015
TI  - Erratum for kang et Al., flexibility and symmetry of prokaryotic genome
      rearrangement reveal lineage-associated core-gene-defined genome organizational
      frameworks.

PMID- 25587014
TI  - Inactivation of a foodborne norovirus outbreak strain with nonthermal atmospheric
      pressure plasma.
AB  - Human norovirus (NoV) is the most frequent cause of epidemic nonbacterial acute
      gastroenteritis worldwide. We investigated the impact of nonthermal or cold
      atmospheric pressure plasma (CAPP) on the inactivation of a clinical human
      outbreak NoV, GII.4. Three different dilutions of a NoV-positive stool sample
      were prepared and subsequently treated with CAPP for various lengths of time, up
      to 15 min. NoV viral loads were quantified by quantitative real-time reverse
      transcription PCR (RT-qPCR). Increased CAPP treatment time led to increased NoV
      reduction; samples treated for the longest time had the lowest viral load. From
      the initial starting quantity of 2.36 * 10(4) genomic equivalents/ml, sample
      exposure to CAPP reduced this value by 1.23 log10 and 1.69 log10 genomic
      equivalents/ml after 10 and 15 min, respectively (P < 0.01). CAPP treatment of
      surfaces carrying a lower viral load reduced NoV by at least 1 log10 after CAPP
      exposure for 2 min (P < 0.05) and 1 min (P < 0.05), respectively. Our results
      suggest that NoV can be inactivated by CAPP treatment. The lack of cell culture
      assays prevents our ability to estimate infectivity. It is possible that some
      detectable, intact virus particles were rendered noninfectious. We conclude that
      CAPP treatment of surfaces may be a useful strategy to reduce the risk of NoV
      transmission in crowded environments. IMPORTANCE: Human gastroenteritis is most
      frequently caused by noroviruses, which are spread person to person and via
      surfaces, often in facilities with crowds of people. Disinfection of surfaces
      that come into contact with infected humans is critical for the prevention of
      cross-contamination and further transmission of the virus. However, effective
      disinfection cannot be done easily in mass catering environments or health care
      facilities. We evaluated the efficacy of cold atmospheric pressure plasma, an
      innovative airborne disinfection method, on surfaces inoculated with norovirus.
      We used a clinically relevant strain of norovirus from an outbreak in Germany.
      Cold plasma was able to inactivate the virus on the tested surfaces, suggesting
      that this method could be used for continuous disinfection of contaminated
      surfaces. The use of a clinical strain of norovirus strengthens the reliability
      of our results as it is a strain relevant to outbreaks in humans.

PMID- 25587016
TI  - The Ordospora colligata genome: Evolution of extreme reduction in microsporidia
      and host-to-parasite horizontal gene transfer.
AB  - Microsporidia are a group of obligate intracellular parasites that are best known
      for their unique infection mechanism and their unparalleled levels of genomic
      reduction and compaction. We sequenced the genome of Ordospora colligata, a gut
      parasite of the microcrustacean Daphnia sp. and the closest known relative to the
      microsporidia characterized by the most extreme genomic reduction, the model
      genus Encephalitozoon. We found that the O. colligata genome is as compact as
      those of Encephalitozoon spp., featuring few introns and a similar complement of
      about 2,000 genes, altogether showing that the extreme reduction took place
      before the origin of Encephalitozoon spp. and their adaptation to vertebrate
      hosts. We also found that the O. colligata genome has acquired by horizontal
      transfer from its animal host a septin that is structurally analogous to septin
      7, a protein that plays a major role in the endocytosis-based invasion mechanism
      of the fungal pathogen Candida albicans. Microsporidian invasion is most often
      characterized by injection through a projectile tube, but microsporidia are also
      known to invade cells by inducing endocytosis. Given the function of septins in
      other systems, we hypothesize that the acquired septin could help O. colligata
      induce its uptake by mimicking host receptors. IMPORTANCE: The smallest known
      eukaryotic genomes are found in members of the Encephalitozoon genus of
      microsporidian parasites. Their extreme compaction, however, is not
      characteristic of the group, whose genomes can differ by an order of magnitude.
      The processes and evolutionary forces that led the Encephalitozoon genomes to
      shed so much of their ancestral baggage are unclear. We sequenced the genome of
      Ordospora colligata, a parasite of the water flea Daphnia sp. and the closest
      known relative of Encephalitozoon species, and show that this extreme reduction
      predated the split between the two lineages. We also found that O. colligata has
      acquired a septin gene by host-to-parasite horizontal transfer and predicted that
      the encoded protein folds like a septin 7, which plays a major role in
      endocytosis. We hypothesize that this acquisition could help O. colligata
      parasitize its hosts by facilitating endocytic infection, a mechanism that occurs
      in microsporidia but that is not yet well understood.

PMID- 25587017
TI  - Can a novel clinical risk score improve pneumonia prediction in acute stroke
      care? A UK multicenter cohort study.
AB  - BACKGROUND: Pneumonia frequently complicates stroke and has a major impact on
      outcome. We derived and internally validated a simple clinical risk score for
      predicting stroke-associated pneumonia (SAP), and compared the performance with
      an existing score (A(2)DS(2)). METHODS AND RESULTS: We extracted data for
      patients with ischemic stroke or intracerebral hemorrhage from the Sentinel
      Stroke National Audit Programme multicenter UK registry. The data were randomly
      allocated into derivation (n=11 551) and validation (n=11 648) samples. A
      multivariable logistic regression model was fitted to the derivation data to
      predict SAP in the first 7 days of admission. The characteristics of the score
      were evaluated using receiver operating characteristics (discrimination) and by
      plotting predicted versus observed SAP frequency in deciles of risk
      (calibration). Prevalence of SAP was 6.7% overall. The final 22-point score
      (ISAN: prestroke Independence [modified Rankin scale], Sex, Age, National
      Institutes of Health Stroke Scale) exhibited good discrimination in the ischemic
      stroke derivation (C-statistic 0.79; 95% CI 0.77 to 0.81) and validation (C
      statistic 0.78; 95% CI 0.76 to 0.80) samples. It was well calibrated in ischemic
      stroke and was further classified into meaningful risk groups (low 0 to 5, medium
      6 to 10, high 11 to 14, and very high >=15) associated with SAP frequencies of
      1.6%, 4.9%, 12.6%, and 26.4%, respectively, in the validation sample.
      Discrimination for both scores was similar, although they performed less well in
      the intracerebral hemorrhage patients with an apparent ceiling effect.
      CONCLUSIONS: The ISAN score is a simple tool for predicting SAP in clinical
      practice. External validation is required in ischemic and hemorrhagic stroke
      cohorts.

PMID- 25587018
TI  - Persistent recovery of normal left ventricular function and dimension in
      idiopathic dilated cardiomyopathy during long-term follow-up: does real healing
      exist?
AB  - BACKGROUND: An important number of patients with idiopathic dilated
      cardiomyopathy have dramatically improved left ventricular function with optimal
      treatment; however, little is known about the evolution and long-term outcome of
      this subgroup, which shows apparent healing. This study assesses whether real
      healing actually exists in dilated cardiomyopathy. METHODS AND RESULTS:
      Persistent apparent healing was evaluated among 408 patients with dilated
      cardiomyopathy receiving tailored medical treatment and followed over the very
      long-term. Persistent apparent healing was defined as left ventricular ejection
      fraction >=50% and indexed left ventricular end-diastolic diameter <=33 mm/m(2)
      at both mid-term (19+/-4 months) and long-term (103+/-9 months) follow-up. At mid
      term, 63 of 408 patients (15%) were apparently healed; 38 (60%; 9%of the whole
      population) showed persistent apparent healing at long-term evaluation. No
      predictors of persistent apparent healing were found. Patients with persistent
      apparent healing showed better heart transplant-free survival at very long-term
      follow-up (95% versus 71%; P=0.014) compared with nonpersistently normalized
      patients. Nevertheless, in the very longterm, 37% of this subgroup experienced
      deterioration of left ventricular systolic function, and 5% died or had heart
      transplantation. CONCLUSIONS: Persistent long-term apparent healing was evident
      in a remarkable proportion of dilated cardiomyopathy patients receiving optimal
      medical treatment and was associated with stable normalization of main clinical
      and laboratory features. This condition can be characterized by a decline of left
      ventricular function over the very long term, highlighting the relevance of
      serial nd individualized follow-up in all patients with dilated cardiomyopathy,
      especially considering the absence of predictors for longterm apparent healing.

PMID- 25587019
TI  - Weighing the risk of drug resistance with the benefits of HIV preexposure
      prophylaxis.

PMID- 25587022
TI  - Saphenous nerve injury after endovenous laser ablation of incompetent greater
      saphenous vein: An electroneuromyography study.
AB  - AIM: To determine whether endovenous laser ablation of incompetent greater
      saphenous vein causes a detectable impairment in saphenous nerve conduction.
      MATERIAL AND METHODS: Thirty-five patients (mean age: 44.78 +/- 8.6, male/female
      ratio: 16/19) who were operated on for incompetent greater saphenous veins,
      underwent electroneuromyography before and two weeks after the operation.
      Dysesthesia was questioned as to whether having unpleasant abnormal sensation
      after the operation. Positive electroneuromyography findings for saphenous nerve
      injury included a sensory nerve action potential amplitude <2 uV or a nerve
      conduction velocity <48.0 m/s or a latency onset >5.0 ms. RESULTS: Thirty-four
      patients were available at two-week follow-up. All patients achieved complete
      proximal closure. Three patients (8.8%) had dysesthesia at two weeks. Mean
      electroneuromyography values were not significantly different between
      preoperative and postoperative period. Postoperatively, none of the patients had
      abnormal sensory nerve action potential or latency onset, whereas nerve
      conduction velocity decreased below the lower limit in two patients. These two
      patients were not among those having dysesthesia and they had no other
      complaints. CONCLUSION: Injury to saphenous nerve seems not likely during
      endovenous laser ablation of incompetent greater saphenous veins, as evidenced by
      normal electroneuromyography values found after the operation.

PMID- 25587020
TI  - Risk of drug resistance among persons acquiring HIV within a randomized clinical
      trial of single- or dual-agent preexposure prophylaxis.
AB  - BACKGROUND: Preexposure prophylaxis (PrEP) with emtricitabine plus tenofovir
      disoproxil fumarate (FTC/TDF) or TDF alone reduces the risk of human
      immunodeficiency virus (HIV) acquisition. Understanding the risk of
      antiretroviral resistance selected by PrEP during breakthrough infections is
      important because of the risk of treatment failure during subsequent
      antiretroviral use. METHODS: Within the largest randomized trial of FTC/TDF
      versus TDF as PrEP, plasma samples were tested for HIV with resistance mutations
      associated with FTC (K65R and M184IV) and TDF (K65R and K70E), using 454
      sequencing. RESULTS: Of 121 HIV seroconverters, 25 received FTC/TDF, 38 received
      TDF, and 58 received placebo. Plasma drug levels in 26 individuals indicated PrEP
      use during or after HIV acquisition, of which 5 had virus with resistance
      mutations associated with their PrEP regimen. Among those with PrEP drug detected
      during infection, resistance was more frequent in the FTC/TDF arm (4 of 7 [57%]),
      compared with the TDF arm (1 of 19 [5.3%]; P = .01), owing to the FTC-associated
      mutation M184IV. Of these cases, 3 had unrecognized acute infection at PrEP
      randomization, and 2 were HIV negative at enrollment. CONCLUSIONS: These results
      suggest that resistance selected by PrEP is rare but can occur both with PrEP
      initiation during acute seronegative HIV infection and in PrEP breakthrough
      infections and that FTC is associated with a greater frequency of resistance
      mutations than TDF.

PMID- 25587021
TI  - Habitat visualization and genomic analysis of "Candidatus Pantoea carbekii," the
      primary symbiont of the brown marmorated stink bug.
AB  - Phytophagous pentatomid insects can negatively impact agricultural productivity
      and the brown marmorated stink bug (Halyomorpha halys) is an emerging invasive
      pest responsible for damage to many fruit crops and ornamental plants in North
      America. Many phytophagous stink bugs, including H. halys, harbor
      gammaproteobacterial symbionts that likely contribute to host development, and
      characterization of symbiont transmission/acquisition and their contribution to
      host fitness may offer alternative strategies for managing pest species.
      "Candidatus Pantoea carbekii" is the primary occupant of gastric ceca lumina
      flanking the distal midgut of H. halys insects and it is acquired each generation
      when nymphs feed on maternal extrachorion secretions following hatching. Insects
      prevented from symbiont uptake exhibit developmental delays and aberrant
      behaviors. To infer contributions of Ca. P. carbekii to H. halys, the complete
      genome was sequenced and annotated from a North American H. halys population.
      Overall, the Ca. P. carbekii genome is nearly one-fourth (1.2 Mb) that of free
      living congenerics, and retains genes encoding many functions that are
      potentially host-supportive. Gene content reflects patterns of gene
      loss/retention typical of intracellular mutualists of plant-feeding insects.
      Electron and fluorescence in situ microscopic imaging of H. halys egg surfaces
      revealed that maternal extrachorion secretions were populated with Ca. P.
      carbekii cells. The reported findings detail a transgenerational mode of symbiont
      transmission distinct from that observed for intracellular insect mutualists and
      illustrate the potential additive functions contributed by the bacterial symbiont
      to this important agricultural pest.

PMID- 25587023
TI  - Hypoxia-inducible factor 1 mediates TAZ expression and nuclear localization to
      induce the breast cancer stem cell phenotype.
AB  - Intratumoral hypoxia, which is associated with breast cancer metastasis and
      patient mortality, increases the percentage of breast cancer stem cells (BCSCs)
      but the underlying molecular mechanisms have not been delineated. Here we report
      that hypoxia-inducible factor 1 (HIF-1) triggers the expression and activity of
      TAZ, a transcriptional co-activator that is required for BCSC maintenance,
      through two discrete mechanisms. First, HIF-1 binds directly to the WWTR1 gene
      and activates transcription of TAZ mRNA. Second, HIF-1 activates transcription of
      the SIAH1 gene, which encodes a ubiquitin protein ligase that is required for the
      hypoxia-induced ubiquitination and proteasome-dependent degradation of LATS2, a
      kinase that inhibits the nuclear localization of TAZ. Inhibition of HIF-1alpha,
      TAZ, or SIAH1 expression by short hairpin RNA blocked the enrichment of BCSCs in
      response to hypoxia. Human breast cancer database analysis revealed that
      increased expression (greater than the median) of both TAZ and HIF-1 target
      genes, but neither one alone, is associated with significantly increased patient
      mortality. Taken together, these results establish a molecular mechanism for
      induction of the BCSC phenotype in response to hypoxia. 

PMID- 25587024
TI  - A unifying gene signature for adenoid cystic cancer identifies parallel MYB
      dependent and MYB-independent therapeutic targets.
AB  - MYB activation is proposed to underlie development of adenoid cystic cancer
      (ACC), an aggressive salivary gland tumor with no effective systemic treatments.
      To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of
      12 ACC with matched normal tissues, and compared these data with 14
      mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We
      detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top
      scoring gene (18-fold induction), however we observed the same signature in ACC
      without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among
      our 12 cases and 3 from public databases) with negligible MYB expression that
      retained the same ACC mRNA signature including over-expression of extracellular
      matrix (ECM) genes. Integration of this signature with somatic mutational
      analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM
      elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB
      expression in human salivary gland cells alters cell morphology and cell adhesion
      in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC
      tumor culture. In summary, we identified a unique ACC signature with parallel MYB
      dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a
      potential target. 

PMID- 25587025
TI  - MYC regulates the non-coding transcriptome.
AB  - Using RNA-seq (RNA sequencing) of ribosome-depleted RNA, we have identified 1,273
      lncRNAs (long non-coding RNAs) in P493-6 human B-cells. Of these, 534 are either
      up- or downregulated in response to MYC overexpression. An increase in MYC
      occupancy near their TSS (transcription start sites) was observed for MYC
      responsive lncRNAs suggesting these are direct MYC targets. MYC binds to the same
      TSS across several cell lines, but the number of TSS bound depends on cellular
      MYC levels and increases with higher MYC concentrations. Despite this concordance
      in promoter binding, a majority of expressed lncRNAs are specific for one cell
      line, suggesting a determinant role of additional, possibly differentiation
      specific factors in the activity of MYC-bound lncRNA promoters. A significant
      fraction of the lncRNA transcripts lack polyadenylation. The RNA-seq data were
      confirmed on eight selected lncRNAs by NRO (nuclear run-on) and RT-qPCR
      (quantitative reverse transcription PCR). 

PMID- 25587026
TI  - Neutrophils with protumor potential could efficiently suppress tumor growth after
      cytokine priming and in presence of normal NK cells.
AB  - In tumor-bearing state, the function of neutrophils is converted from tumor
      suppressing to tumor-promoting. Here we report that priming with IFN-gamma and
      TNF-alpha could convert the potential of neutrophils from tumor-promoting to
      tumor-suppressing. The neutrophils with protumor potential have not lost their
      responsiveness to IFN-gamma and TNF-alpha. After priming with IFN-gamma and TNF
      alpha, the potential of the neutrophils to express Bv8 and Mmp9 genes was
      reduced. Conversely, the tumor-promotional neutrophils recovered the expression
      of Rab27a and Trail, resumed the activation levels of PI3K and p38 MAPK pathways
      in response to stimuli, and expressed higher levels of IL-18 and NK-activating
      ligands such as RAE-1, MULT-1, and H60. Therefore, the anti-tumor function of the
      neutrophils was augmented, including the cytotoxicity to tumor cells, the
      capability of degranulation, and the capacity to activate NK cells. Since the
      function of NK cells is impaired in tumor-bearing state, the administration of
      normal NK cells could significantly augment the efficiency of tumor therapy based
      on neutrophil priming. These findings highlight the reversibility of neutrophil
      function in tumor-bearing state, and suggest that neutrophil priming by IFN
      gamma/TNF-alpha might be a potential approach to eliminate residual tumor cells
      in comprehensive strategy for tumor therapy. 

PMID- 25587027
TI  - The p53 transcriptional pathway is preserved in ATMmutated and NOTCH1mutated
      chronic lymphocytic leukemias.
AB  - By using next generation sequencing, we have analyzed 108 B chronic lymphocytic
      leukemia (B-CLL) patients. Among genes involved in the TP53 pathway, we found
      frequent mutations in ATM (n=18), TP53 (n=10) and NOTCH1 (n=10) genes, rare
      mutations of NOTCH2 (n=2) and CDKN1A/p21 (n=1) and no mutations in BAX, MDM2,
      TNFRSF10A and TNFRSF10B genes. The in vitro treatment of primary B-CLL cells with
      the activator of p53 Nutlin-3 induced the transcription of p53 target genes,
      without significant differences between the B-CLL without mutations and those
      harboring either ATM or NOTCH1mutations. On the other hand, the subgroup of
      TP53mutated B-CLL exhibited a significantly lower induction of the p53 target
      genes in response to Nutlin-3 as compared to the other B-CLL samples. However,
      among the TP53mutated B-CLL, those showing mutations in the high hot spot region
      of the DNA binding domain [273-280 aa] maintained a significantly higher p53
      dependent transcriptional activity as compared to the other TP53mutated B-CLL
      samples. Since the ability to elicit a p53-dependent transcriptional activity in
      vitro has a positive prognostic significance, our data suggest that ATMmutated,
      NOTCH1mutated and surprisingly, also a subset of TP53mutated B-CLL patients might
      benefit from therapeutic combinations including small molecule activator of the
      p53 pathway. 

PMID- 25587028
TI  - Ferroxitosis: a cell death from modulation of oxidative phosphorylation and PKM2
      dependent glycolysis in melanoma.
AB  - Reliance on glycolysis is a characteristic of malignancy, yet the development of
      resistance to BRAF inhibitors in melanoma is associated with gain of
      mitochondrial function. Concurrent attenuation of oxidative phosphorylation and
      HIF-1alpha/PKM2-dependent glycolysis promotes a non-apoptotic, iron- and oxygen
      dependent cell death that we term ferroxitosis. The redox cycling agent menadione
      causes a robust increase in oxygen consumption, accompanied by significant loss
      of intracellular ATP and rapid cell death. Conversely, either hypoxic adaptation
      or iron chelation prevents menadione-induced ferroxitosis. Ectopic expression of
      K213Q HIF-1alpha mutant blunts the effects of menadione. However, knockdown of
      HIF-1alpha or PKM2 restores menadione-induced cytotoxicity in hypoxia. Similarly,
      exposure of melanoma cells to shikonin, a menadione analog and a potential PKM2
      inhibitor, is sufficient to induce ferroxitosis under hypoxic conditions.
      Collectively, our findings reveal that ferroxitosis curtails metabolic plasticity
      in melanoma. 

PMID- 25587029
TI  - Mislocalization of p27 to the cytoplasm of breast cancer cells confers resistance
      to anti-HER2 targeted therapy.
AB  - As a cell cycle inhibitor and tumor suppressor, p27 is frequently misregulated in
      human cancers. Increased degradation is the most common mechanism of
      misregulation, however in some cancers, p27 is mislocalized from its cell cycle
      inhibitory location in the nucleus, to the cytoplasm. In normal cells cytoplasmic
      p27 has functions that are distinct from its cell cycle-regulatory nuclear
      functions. Therefore, an important question is whether localization of p27 to the
      cytoplasm in tumor cells is primarily a mechanism for cancelling its inhibitory
      effect on cell proliferation, or whether cytoplasmic p27 has more direct
      oncogenic actions. To study p27 mislocalization in human cancers we screened a
      panel of common breast cancer cell lines. We observed that p27 accumulated in the
      cytoplasm exclusively in cell lines that are Her2+. To address the significance
      of p27 mislocalization in Her2+ breast cancer cells we interrogated the cellular
      response to the dual-Her2/EGFR kinase inhibitor, lapatinib. Knockdown of p27
      using shRNA sensitized Her2+ cells to lapatinib-induced apoptosis. Moreover,
      expression of a constitutively cytoplasmic form of p27 (p27DeltaNLS) reversed the
      lapatinib-induced apoptosis, suggesting that cytoplasmic p27 contributed to
      lapatinib resistance in Her2+ breast cancer cells by suppressing apoptosis. Our
      results suggest that p27 localization may be useful as a predictive biomarker of
      therapeutic response in patients with Her2+ breast cancers. 

PMID- 25587031
TI  - The angular structure of ONC201, a TRAIL pathway-inducing compound, determines
      its potent anti-cancer activity.
AB  - We previously identified TRAIL-inducing compound 10 (TIC10), also known as
      NSC350625 or ONC201, from a NCI chemical library screen as a small molecule that
      has potent anti-tumor efficacy and a benign safety profile in preclinical cancer
      models. The chemical structure that was originally published by Stahle, et. al.
      in the patent literature was described as an imidazo[1,2-a]pyrido[4,3
      d]pyrimidine derivative. The NCI and others generally accepted this as the
      correct structure, which was consistent with the mass spectrometry analysis
      outlined in the publication by Allen et. al. that first reported the molecule's
      anticancer properties. A recent publication demonstrated that the chemical
      structure of ONC201 material from the NCI is an angular [3,4-e] isomer of the
      originally disclosed, linear [4,3-d] structure. Here we confirm by NMR and X-ray
      structural analysis of the dihydrochloride salt form that the ONC201 material
      produced by Oncoceutics is the angular [3,4-e] structure and not the linear
      structure originally depicted in the patent literature and by the NCI. Similarly,
      in accordance with our biological evaluation, the previously disclosed anti
      cancer activity is associated with the angular structure and not the linear
      isomer. Together these studies confirm that ONC201, produced by Oncoceutics or
      obtained from the NCI, possesses an angular [3,4-e] structure that represents the
      highly active anti-cancer compound utilized in prior preclinical studies and now
      entering clinical trials in advanced cancers. 

PMID- 25587030
TI  - Tumor promoter-induced cellular senescence: cell cycle arrest followed by
      geroconversion.
AB  - Phorbol ester (PMA or TPA), a tumor promoter, can cause either proliferation or
      cell cycle arrest, depending on cellular context. For example, in SKBr3 breast
      cancer cells, PMA hyper-activates the MEK/MAPK pathway, thus inducing p21 and
      cell cycle arrest. Here we showed that PMA-induced arrest was followed by
      conversion to cellular senescence (geroconversion). Geroconversion was associated
      with active mTOR and S6 kinase (S6K). Rapamycin suppressed geroconversion,
      maintaining quiescence instead. In this model, PMA induced arrest (step one of a
      senescence program), whereas constitutively active mTOR drove geroconversion
      (step two). Without affecting Akt phosphorylation, PMA increased phosphorylation
      of S6K (T389) and S6 (S240/244), and that was completely prevented by rapamycin.
      Yet, T421/S424 and S235/236 (p-S6K and p-S6, respectively) phosphorylation became
      rapamycin-insensitive in the presence of PMA. Either MEK or mTOR was sufficient
      to phosphorylate these PMA-induced rapamycin-resistant sites because co-treatment
      with U0126 and rapamycin was required to abrogate them. We next tested whether
      activation of rapamycin-insensitive pathways would shift quiescence towards
      senescence. In HT-p21 cells, cell cycle arrest was caused by IPTG-inducible p21
      and was spontaneously followed by mTOR-dependent geroconversion. Rapamycin
      suppressed geroconversion, whereas PMA partially counteracted the effect of
      rapamycin, revealing the involvement of rapamycin-insensitive gerogenic pathways.
      In normal RPE cells arrested by serum withdrawal, the mTOR/pS6 pathway was
      inhibited and cells remained quiescent. PMA transiently activated mTOR, enabling
      partial geroconversion. We conclude that PMA can initiate a senescent program by
      either inducing arrest or fostering geroconversion or both. Rapamycin can
      decrease gero-conversion by PMA, without preventing PMA-induced arrest. The tumor
      promoter PMA is a gero-promoter, which may be useful to study aging in mammals. 

PMID- 25587032
TI  - Peripheral primitive neuroectodermal tumor: dynamic CT, MRI and
      clinicopathological characteristics--analysis of 36 cases and review of the
      literature.
AB  - BACKGROUND: The peripheral primitive neuroectodermal tumor (pPNET) is a rare
      malignant tumor originating from neuroectoderm. The accurate diagnosis is
      essential for the treatment of pPNET. METHODS: we performed the largest cases of
      retrospective analysis thus far to review the unique computed tomography (CT),
      magnetic resonance imaging (MRI), and clinicopathological features of pPNET. The
      tumor location, morphological features, signal intensity, contrast enhancement
      characteristics, and involvement of local soft tissues of 36 pPNETs were
      assessed. RESULTS: Our results showed that there were more men (25/36) than women
      pPNETs patients. Unenhanced MRI (16 cases) showed that 14 cases were isointense
      and 2 cases were hypointense on T1WI. Nine cases were isointense and 7 were
      hyperintense on T2WI. Most pPNETs had heterogeneous signal intensity with small
      necrosis (CT: 31/36; MRI: 14/16) as well as heterogeneous enhancement (CT: 34/30;
      MRI: 15/16). The tumors usually had ill-defined borders and irregular shapes (CT:
      30/36; MRI: 15/16). Pathologic exam showed small areas of necrosis in all tumors.
      CONCLUSIONS: The diagnosis of pPNET should be suggested in young men when the
      imaging depicts a single large ill-defined solid mass with small area of
      necrosis, especially for those whose images show iso-intense on T1WI and T2WI and
      have heterogeneous enhancement.

PMID- 25587033
TI  - Tyrosine phosphorylation of the Lyn Src homology 2 (SH2) domain modulates its
      binding affinity and specificity.
AB  - Src homology 2 (SH2) domains are modular protein structures that bind
      phosphotyrosine (pY)-containing polypeptides and regulate cellular functions
      through protein-protein interactions. Proteomics analysis showed that the SH2
      domains of Src family kinases are themselves tyrosine phosphorylated in blood
      system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia,
      and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we
      found that phosphorylation at the conserved SH2 domain residue Y(194) impacts the
      affinity and specificity of SH2 domain binding to pY-containing peptides and
      proteins. Analysis of the Lyn SH2 domain crystal structure supports a model
      wherein phosphorylation of Y(194) on the EF loop modulates the binding pocket
      that engages amino acid side chains at the pY+2/+3 position. These data indicate
      another level of regulation wherein SH2-mediated protein-protein interactions are
      modulated by SH2 kinases and phosphatases. 

PMID- 25587034
TI  - Proteomic study of microsomal proteins reveals a key role for Arabidopsis annexin
      1 in mediating heat stress-induced increase in intracellular calcium levels.
AB  - To understand the early signaling steps in the response of plant cells to
      increased environmental temperature, 2-D difference gel electrophoresis was used
      to study the proteins in microsomes of Arabidopsis seedlings that are regulated
      early during heat stress. Using mass spectrometry, 19 microsomal proteins that
      showed an altered expression level within 5 min after heat treatment were
      identified. Among these proteins, annexin 1 (AtANN1) was one of those up
      regulated rapidly after heat-shock treatment. Functional studies show loss-of
      function mutants for AtANN1 and its close homolog AtANN2 were more sensitive to
      heat-shock treatment, whereas plants overexpressing AtANN1 showed more resistance
      to this treatment. Correspondingly, the heat-induced expression of heat-shock
      proteins and heat-shock factors is inhibited in ann1/ann2 double mutant, and the
      heat-activated increase in cytoplasmic calcium concentration ([Ca(2+)]cyt) is
      greatly impaired in the ann1 mutant and almost undetectable in ann1/ann2 double
      mutant. Taken together these results suggest that AtANN1 is important in
      regulating the heat-induced increase in [Ca(2+)]cyt and in the response of
      Arabidopsis seedlings to heat stress. 

PMID- 25587037
TI  - How I treat relapsed myeloma.
AB  - Multiple myeloma (MM) is a plasma cell malignancy leading to significant life
      expectancy shortening. Although the incorporation of the novel agents
      thalidomide, bortezomib, and lenalidomide in the front-line therapy has resulted
      in significant improvement, almost all patients relapse, making the treatment of
      relapse a real challenge. In the present article, when and how to treat relapsed
      MM is discussed. Treatment can be safely delayed in a subset of patients with
      asymptomatic relapse, whereas those with symptomatic relapse, advanced disease at
      diagnosis, or significant paraproteinemic increase require prompt rescue therapy.
      The benefit of retreatment and the use of a sequential approach for successive
      relapses considering drug synergism are highlighted. For patients with aggressive
      relapses and for those who have exhausted all available options, continued
      therapy until disease progression is recommended, particularly when using
      regimens with a long-term safety profile. Patients with a duration response to a
      first autologous stem cell transplantation (ASCT) longer than 2 years may benefit
      from a second ASCT. Patients with aggressive disease and/or poor cytogenetics at
      diagnosis relapsing within the first 2 years from ASCT should be considered for
      an allogeneic transplantation. Finally, a number of newer promising drugs are
      being actively investigated and the enrolment of patients in clinical trials is
      encouraged. 

PMID- 25587035
TI  - Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle
      erythrocyte sphingosine kinase 1 activity.
AB  - Erythrocyte possesses high sphingosine kinase 1 (SphK1) activity and is the major
      cell type supplying plasma sphingosine-1-phosphate, a signaling lipid regulating
      multiple physiological and pathological functions. Recent studies revealed that
      erythrocyte SphK1 activity is upregulated in sickle cell disease (SCD) and
      contributes to sickling and disease progression. However, how erythrocyte SphK1
      activity is regulated remains unknown. Here we report that adenosine induces
      SphK1 activity in human and mouse sickle and normal erythrocytes in vitro. Next,
      using 4 adenosine receptor-deficient mice and pharmacological approaches, we
      determined that the A2B adenosine receptor (ADORA2B) is essential for adenosine
      induced SphK1 activity in human and mouse normal and sickle erythrocytes in
      vitro. Subsequently, we provide in vivo genetic evidence that adenosine deaminase
      (ADA) deficiency leads to excess plasma adenosine and elevated erythrocyte SphK1
      activity. Lowering adenosine by ADA enzyme therapy or genetic deletion of ADORA2B
      significantly reduced excess adenosine-induced erythrocyte SphK1 activity in ADA
      deficient mice. Finally, we revealed that protein kinase A-mediated extracellular
      signal-regulated kinase 1/2 activation functioning downstream of ADORA2B
      underlies adenosine-induced erythrocyte SphK1 activity. Overall, our findings
      reveal a novel signaling network regulating erythrocyte SphK1 and highlight
      innovative mechanisms regulating SphK1 activity in normal and SCD. 

PMID- 25587038
TI  - Interaction of kindlin-2 with integrin beta3 promotes outside-in signaling
      responses by the alphaVbeta3 vitronectin receptor.
AB  - The bidirectional signaling and hemostatic functions of platelet alphaIIbbeta3
      are regulated by kindlin-3 through interactions with the beta3 cytoplasmic tail.
      Little is known about kindlin regulation of the related "vitronectin receptor,"
      alphaVbeta3. These relationships were investigated in endothelial cells, which
      express alphaVbeta3 and kindlin-2 endogenously. "beta3DeltaRGT" knock-in mice
      lack the 3 C-terminal beta3 tail residues, whereas in "beta3/beta1(EGK)" mice,
      RGT is replaced by the corresponding residues of beta1. The wild-type beta3 tail
      pulled down kindlin-2 and c-Src in vitro, whereas beta3DeltaRGT bound neither
      protein and beta3/beta1(EGK) bound kindlin-2, but not c-Src. beta3DeltaRGT
      endothelial cells, but not beta3/beta1(EGK) endothelial cells, exhibited
      migration and spreading defects on vitronectin and reduced sprouting in 3
      dimensional fibrin. Short hairpin RNA silencing of kindlin-2, but not c-Src,
      blocked sprouting by beta3 wild-type endothelial cells. Moreover, defective
      sprouting by beta3DeltaRGT endothelial cells could be rescued by conditional,
      forced interaction of alphaVbeta3DeltaRGT with kindlin-2. Stimulation of
      beta3DeltaRGT endothelial cells led to normal extracellular ligand binding to
      alphaVbeta3, pin-pointing their defect to one of outside-in alphaVbeta3
      signaling. beta3DeltaRGT mice, but not beta3/beta1(EGK) mice, exhibited defects
      in both developmental and tumor angiogenesis, responses that require endothelial
      cell function. Thus, the beta3/kindlin-2 interaction promotes outside-in
      alphaVbeta3 signaling selectively, with biological consequences in vivo. 

PMID- 25587036
TI  - Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on
      hemogenic endothelium.
AB  - Hematopoietic and vascular development share many common features, including cell
      surface markers and sites of origin. Recent lineage-tracing studies have
      established that definitive hematopoietic stem and progenitor cells arise from
      vascular endothelial-cadherin(+) hemogenic endothelial cells of the aorta-gonad
      mesonephros region, but the genetic programs underlying the specification of
      hemogenic endothelial cells remain poorly defined. Here, we discovered that Notch
      induction enhances hematopoietic potential and promotes the specification of
      hemogenic endothelium in differentiating cultures of mouse embryonic stem cells,
      and we identified Foxc2 as a highly upregulated transcript in the hemogenic
      endothelial population. Studies in zebrafish and mouse embryos revealed that
      Foxc2 and its orthologs are required for the proper development of definitive
      hematopoiesis and function downstream of Notch signaling in the hemogenic
      endothelium. These data establish a pathway linking Notch signaling to Foxc2 in
      hemogenic endothelial cells to promote definitive hematopoiesis. 

PMID- 25587039
TI  - Activated factor XI increases the procoagulant activity of the extrinsic pathway
      by inactivating tissue factor pathway inhibitor.
AB  - Activation of coagulation factor XI (FXI) may play a role in hemostasis. The
      primary substrate of activated FXI (FXIa) is FIX, leading to FX activation (FXa)
      and thrombin generation. However, recent studies suggest the hemostatic role of
      FXI may not be restricted to the activation of FIX. We explored whether FXI could
      interact with and inhibit the activity of tissue factor pathway inhibitor (TFPI).
      TFPI is an essential reversible inhibitor of activated factor X (FXa) and also
      inhibits the FVIIa-TF complex. We found that FXIa neutralized both endothelium-
      and platelet-derived TFPI by cleaving the protein between the Kunitz (K) 1 and K2
      domains (Lys86/Thr87) and at the active sites of the K2 (Arg107/Gly108) and K3
      (Arg199/Ala200) domains. Addition of FXIa to plasma was able to reverse the
      ability of TFPI to prolong TF-initiated clotting times in FXI- or FIX-deficient
      plasma, as well as FXa-initiated clotting times in FX-deficient plasma. Treatment
      of cultured endothelial cells with FXIa increased the generation of FXa and
      promoted TF-dependent fibrin formation in recalcified plasma. Together, these
      results suggest that the hemostatic role of FXIa may be attributed not only to
      activation of FIX but also to promoting the extrinsic pathway of thrombin
      generation through inactivation of TFPI. 

PMID- 25587041
TI  - Parmodulins inhibit thrombus formation without inducing endothelial injury caused
      by vorapaxar.
AB  - Protease-activated receptor-1 (PAR1) couples the coagulation cascade to platelet
      activation during myocardial infarction and to endothelial inflammation during
      sepsis. This receptor demonstrates marked signaling bias. Its activation by
      thrombin stimulates prothrombotic and proinflammatory signaling, whereas its
      activation by activated protein C (APC) stimulates cytoprotective and
      antiinflammatory signaling. A challenge in developing PAR1-targeted therapies is
      to inhibit detrimental signaling while sparing beneficial pathways. We now
      characterize a novel class of structurally unrelated small-molecule PAR1
      antagonists, termed parmodulins, and compare the activity of these compounds to
      previously characterized compounds that act at the PAR1 ligand-binding site. We
      find that parmodulins target the cytoplasmic face of PAR1 without modifying the
      ligand-binding site, blocking signaling through Galphaq but not Galpha13 in vitro
      and thrombus formation in vivo. In endothelium, parmodulins inhibit prothrombotic
      and proinflammatory signaling without blocking APC-mediated pathways or inducing
      endothelial injury. In contrast, orthosteric PAR1 antagonists such as vorapaxar
      inhibit all signaling downstream of PAR1. Furthermore, exposure of endothelial
      cells to nanomolar concentrations of vorapaxar induces endothelial cell barrier
      dysfunction and apoptosis. These studies demonstrate how functionally selective
      antagonism can be achieved by targeting the cytoplasmic face of a G-protein
      coupled receptor to selectively block pathologic signaling while preserving
      cytoprotective pathways. 

PMID- 25587043
TI  - Paternalistic breaches of confidentiality in prison: mental health professionals'
      attitudes and justifications.
AB  - AIM: This manuscript presents mental health practitioners' (MHPs) practice,
      attitudes and justifications for breaching confidentiality when imprisoned
      patients disclose suicidal thoughts or abuse by others. METHODS: 24 MHPs working
      in Swiss prisons shared their experiences regarding confidentiality practices.
      The data were analysed qualitatively and MHPs' attitudes and course of action
      were identified. RESULTS: Analysis revealed paternalistic breaches of
      confidentiality. When patients reported suicidal thoughts and abuse, MHPs
      believed that forgoing confidentiality is necessary to protect patients,
      providing several justifications for it. Patients were informed that such
      information will be transmitted without their consent to medical and non-medical
      prison personnel. With reference to suicidal attempts, MHPs resorted to methods
      that may reduce suicidal attempts such as transfer to hospital or internal
      changes in living arrangements, which would require provision of certain
      information to prison guards. In cases of abuse, some MHPs convinced patients to
      accept intervention or sometimes overrode competent patients' refusals to report.
      Also in the case of abuse, provision of limited information to other prison
      personnel was seen as an acceptable method to protect patients from further harm.
      DISCUSSION: Breaches of confidentiality, whether limited or full, remain
      unethical, when used for competent patients based solely on paternalistic
      justifications. Institutionalising ethical and legal procedures to address
      suicidal and abuse situations would be helpful. Education and training to help
      both medical and prison personnel to respond to such situations in an appropriate
      manner that ensures confidentiality and protects patients from suicide and abuse
      are necessary.

PMID- 25587042
TI  - JMJD3 promotes chondrocyte proliferation and hypertrophy during endochondral bone
      formation in mice.
AB  - JMJD3 (KDM6B) is an H3K27me3 demethylase and counteracts polycomb-mediated
      transcription repression. However, the function of JMJD3 in vivo is not well
      understood. Here we show that JMJD3 is highly expressed in cells of the
      chondrocyte lineage, especially in prehypertrophic and hypertrophic chondrocytes,
      during endochondral ossification. Homozygous deletion of Jmjd3 results in
      severely decreased proliferation and delayed hypertrophy of chondrocytes, and
      thereby marked retardation of endochondral ossification in mice. Genetically,
      JMJD3 associates with RUNX2 to promote proliferation and hypertrophy of
      chondrocytes. Biochemically, JMJD3 associates with and enhances RUNX2 activity by
      derepression of Runx2 and Ihh transcription through its H3K27me3 demethylase
      activity. These results demonstrate that JMJD3 is a key epigenetic regulator in
      the process of cartilage maturation during endochondral bone formation. 

PMID- 25587044
TI  - Role of Hic-5 in the formation of microvilli-like structures and the monocyte
      endothelial interaction that accelerates atherosclerosis.
AB  - AIMS: The adhesion of circulating monocytes to endothelial cells (ECs) is an
      early and critical event in the formation of atherosclerotic plaques. Hydrogen
      peroxide-inducible clone 5 (Hic-5) serves as an adaptor molecule in cell adhesion
      complexes. However, the role of endothelial Hic-5 in monocyte-EC interaction and
      atherogenesis remains unclear. We examined the roles of endothelial Hic-5 in
      monocyte-EC interaction and atherogenesis using mouse models of atherosclerosis
      and cultured human umbilical vein endothelial cells (HUVECs). METHODS AND
      RESULTS: Hic-5 was expressed in ECs, but not in monocytes/macrophages. An ex vivo
      monocyte adhesion assay revealed that adhesion of THP-1 monocytes to aortas
      isolated from Apoe(-/-) and LDLR(-/-) mice stimulated by TNF-alpha or oxidized
      LDL was suppressed by Hic-5 deficiency. Scanning electron microscopic
      observations of aortas harvested from Apoe(-/-) mice revealed that TNF-alpha- or
      oxidized LDL-induced microvilli-like structures were markedly suppressed by Hic-5
      deficiency. Relative Hic-5 deficiency suppressed 60% of the atherosclerotic
      lesions in aortas from Apoe(-/-) and LDLR(-/-) mice. In contrast, overexpression
      of Hic-5 in HUVECs promoted induction of microvilli-like structures and adherence
      of THP-1 cells in an adhesion receptor such as intercellular adhesion molecule-1-
      and vascular cell adhesion molecule-1-dependent manner. CONCLUSION: Hic-5 in ECs
      plays an important role in the formation of microvilli-like structures and in the
      interaction between ECs and monocytes, leading to monocyte recruitment and
      subsequent development of atherosclerosis.

PMID- 25587045
TI  - Syndecan-4 is a key determinant of collagen cross-linking and passive myocardial
      stiffness in the pressure-overloaded heart.
AB  - AIMS: Diastolic dysfunction is central to the development of heart failure. To
      date, there is no effective treatment and only limited understanding of its
      molecular basis. Recently, we showed that the transmembrane proteoglycan syndecan
      4 increases in the left ventricle after pressure overload in mice and man, and
      that syndecan-4 via calcineurin/nuclear factor of activated T-cells (NFAT)
      promotes myofibroblast differentiation and collagen production upon mechanical
      stress. The aim of this study was to investigate whether syndecan-4 affects
      collagen cross-linking and myocardial stiffening in the pressure-overloaded
      heart. METHODS AND RESULTS: Aortic banding (AB) caused concentric hypertrophy and
      increased passive tension of left ventricular muscle strips, responses that were
      blunted in syndecan-4(-/-) mice. Disruption of titin anchoring by salt extraction
      of actin and myosin filaments revealed that the effect of syndecan-4 on passive
      tension was due to extracellular matrix remodelling. Expression and activity of
      the cross-linking enzyme lysyl oxidase (LOX) increased with mechanical stress and
      was lower in left ventricles and cardiac fibroblasts from syndecan-4(-/-) mice,
      which exhibited less collagen cross-linking after AB. Expression of osteopontin
      (OPN), a matricellular protein able to induce LOX in cardiac fibroblasts, was up
      regulated in hearts after AB, in mechanically stressed fibroblasts and in
      fibroblasts overexpressing syndecan-4, calcineurin, or NFAT, but down-regulated
      in fibroblasts lacking syndecan-4 or after NFAT inhibition. Interestingly, the
      extracellular domain of syndecan-4 facilitated LOX-mediated collagen cross
      linking. CONCLUSIONS: Syndecan-4 exerts a dual role in collagen cross-linking,
      one involving its cytosolic domain and NFAT signalling leading to collagen, OPN,
      and LOX induction in cardiac fibroblasts; the other involving the extracellular
      domain promoting LOX-dependent cross-linking.

PMID- 25587047
TI  - Systemic gene transfer enables optogenetic pacing of mouse hearts.
AB  - AIMS: Optogenetic pacing of the heart has been demonstrated in transgenic animals
      expressing channelrhodopsin-2 (ChR2). However, for the clinical use of
      optogenetics to treat cardiac arrhythmias, gene transfer to non-transgenic hearts
      is required. The aim of this study was to describe a reliable method for gene
      transfer of ChR2 into a sufficient percentage of cardiomyocytes to overcome the
      electrical sink of all the coupled non-expressing cardiomyocytes during optical
      pacing of the whole heart in vivo. METHODS AND RESULTS: Adeno-associated virus
      (AAV) with cardiac tropism for expression of ChR2 in fusion with mCherry was
      systemically injected into wild-type mouse hearts. Bright mCherry fluorescence
      was detected in the whole heart 4-10 weeks later. Single-cell dissociation
      revealed that on average 58% cardiomyocytes were mCherry-positive. These showed
      light-induced inward currents, action potentials, and contractions. Pulsed
      illumination of the left ventricle induced ventricular pacing in vivo in 74% of
      mice, and higher light intensities were required for reduced pulse duration or
      size of illumination. Non-responding hearts showed low AAV expression, and the
      threshold for optical pacing was estimated to be 35-40% ChR2-expressing
      cardiomyocytes. Optical pacing in vivo was stable over extended periods without
      negative effects on normal sinus rhythm and ECG parameters after termination of
      stimulation indicating sufficient cardiac output during pacing. CONCLUSIONS: Gene
      transfer generates sufficient ChR2 photocurrent for reliable optogenetic pacing
      in vivo and lays out the basis for future optogenetic pacemaker and pain-free
      defibrillation therapies.

PMID- 25587046
TI  - Decreasing mitochondrial fission diminishes vascular smooth muscle cell migration
      and ameliorates intimal hyperplasia.
AB  - AIMS: Vascular smooth muscle cell (VSMC) migration in response to arterial wall
      injury is a critical process in the development of intimal hyperplasia. Cell
      migration is an energy-demanding process that is predicted to require
      mitochondrial function. Mitochondria are morphologically dynamic, undergoing
      continuous shape change through fission and fusion. However, the role of
      mitochondrial morphology in VSMC migration is not well understood. The aim of the
      study is to understand how mitochondrial fission contributes to VSMC migration
      and provides its in vivo relevance in the mouse model of intimal hyperplasia.
      METHODS AND RESULTS: In primary mouse VSMCs, the chemoattractant PDGF induced
      mitochondrial shortening through the mitochondrial fission protein dynamin-like
      protein 1 (DLP1)/Drp1. Perturbation of mitochondrial fission by expressing the
      dominant-negative mutant DLP1-K38A or by DLP1 silencing greatly decreased PDGF
      induced lamellipodia formation and VSMC migration, indicating that mitochondrial
      fission is an important process in VSMC migration. PDGF induced an augmentation
      of mitochondrial energetics as well as ROS production, both of which were found
      to be necessary for VSMC migration. Mechanistically, the inhibition of
      mitochondrial fission induced an increase of mitochondrial inner membrane proton
      leak in VSMCs, abrogating the PDGF-induced energetic enhancement and an ROS
      increase. In an in vivo model of intimal hyperplasia, transgenic mice expressing
      DLP1-K38A displayed markedly reduced ROS levels and neointima formation in
      response to femoral artery wire injury. CONCLUSIONS: Mitochondrial fission is an
      integral process in cell migration, and controlling mitochondrial fission can
      limit VSMC migration and the pathological intimal hyperplasia by altering
      mitochondrial energetics and ROS levels.

PMID- 25587049
TI  - Without mandatory regulation, clinical physiologists put patients at risk.

PMID- 25587050
TI  - A constructionist review of morality and emotions: no evidence for specific links
      between moral content and discrete emotions.
AB  - Morality and emotions are linked, but what is the nature of their correspondence?
      Many "whole number" accounts posit specific correspondences between moral content
      and discrete emotions, such that harm is linked to anger, and purity is linked to
      disgust. A review of the literature provides little support for these specific
      morality-emotion links. Moreover, any apparent specificity may arise from global
      features shared between morality and emotion, such as affect and conceptual
      content. These findings are consistent with a constructionist perspective of the
      mind, which argues against a whole number of discrete and domain-specific mental
      mechanisms underlying morality and emotion. Instead, constructionism emphasizes
      the flexible combination of basic and domain-general ingredients such as core
      affect and conceptualization in creating the experience of moral judgments and
      discrete emotions. The implications of constructionism in moral psychology are
      discussed, and we propose an experimental framework for rigorously testing
      morality-emotion links. 

PMID- 25587048
TI  - Atrial fibrillation: effects beyond the atrium?
AB  - Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is
      associated with significant morbidity, mostly secondary to heart failure and
      stroke, and an estimated two-fold increase in premature death. Efforts to
      increase our understanding of AF and its complications have focused on
      unravelling the mechanisms of electrical and structural remodelling of the atrial
      myocardium. Yet, it is increasingly recognized that AF is more than an atrial
      disease, being associated with systemic inflammation, endothelial dysfunction,
      and adverse effects on the structure and function of the left ventricular
      myocardium that may be prognostically important. Here, we review the molecular
      and in vivo evidence that underpins current knowledge regarding the effects of
      human or experimental AF on the ventricular myocardium. Potential mechanisms are
      explored including diffuse ventricular fibrosis, focal myocardial scarring, and
      impaired myocardial perfusion and perfusion reserve. The complex relationship
      between AF, systemic inflammation, as well as endothelial/microvascular
      dysfunction and the effects of AF on ventricular calcium handling and oxidative
      stress are also addressed. Finally, consideration is given to the clinical
      implications of these observations and concepts, with particular reference to
      rate vs. rhythm control. 

PMID- 25587052
TI  - Is widespread screening for hepatitis C justified?

PMID- 25587040
TI  - Role of allogeneic stem cell transplantation in adult patients with Ph-negative
      acute lymphoblastic leukemia.
AB  - Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic
      Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with
      Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic
      stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL
      2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at
      least 1 conventional high-risk factor were candidates for SCT in first complete
      remission. Among these, 282 (54%) received a transplant in first complete
      remission. At 3 years, posttransplant cumulative incidences of relapse,
      nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%,
      15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a
      significant difference in RFS between SCT and no-SCT cohorts. However, SCT was
      associated with longer RFS in patients with postinduction minimal residual
      disease (MRD) >=10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B
      cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion
      (hazard ratio, 0.42). This article shows that poor early MRD response, in
      contrast to conventional ALL risk factors, is an excellent tool to identify
      patients who may benefit from allogeneic SCT in the context of intensified adult
      ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as
      #NCT00222027; GRAALL-2005 was registered as #NCT00327678. 

PMID- 25587051
TI  - Association of the colorectal CpG island methylator phenotype with molecular
      features, risk factors, and family history.
AB  - BACKGROUND: The CpG island methylator phenotype (CIMP) represents a subset of
      colorectal cancers characterized by widespread aberrant DNA hypermethylation at
      select CpG islands. The risk factors and environmental exposures contributing to
      etiologic heterogeneity between CIMP and non-CIMP tumors are not known. METHODS:
      We measured the CIMP status of 3,119 primary population-based colorectal cancer
      tumors from the multinational Colon Cancer Family Registry. Etiologic
      heterogeneity was assessed by a case-case study comparing risk factor frequency
      of colorectal cancer cases with CIMP and non-CIMP tumors using logistic
      regression to estimate the case-case odds ratio (ccOR). RESULTS: We found
      associations between tumor CIMP status and MSI-H (ccOR = 7.6), BRAF V600E
      mutation (ccOR = 59.8), proximal tumor site (ccOR = 9; all P < 0.0001), female
      sex [ccOR = 1.8; 95% confidence interval (CI), 1.5-2.1], older age (ccOR = 4.0
      comparing over 70 years vs. under 50; 95% CI, 3.0-5.5), and family history of CRC
      (ccOR = 0.6; 95% CI, 0.5-0.7). While use of NSAIDs varied by tumor CIMP status
      for both males and females (P = 0.0001 and P = 0.02, respectively), use of
      multivitamin or calcium supplements did not. Only for female colorectal cancer
      was CIMP status associated with increased pack-years of smoking (Ptrend < 0.001)
      and body mass index (BMI; Ptrend = 0.03). CONCLUSIONS: The frequency of several
      colorectal cancer risk factors varied by CIMP status, and the associations of
      smoking and obesity with tumor subtype were evident only for females. IMPACT:
      Differences in the associations of a unique DNA methylation-based subgroup of
      colorectal cancer with important lifestyle and environmental exposures increase
      understanding of the molecular pathologic epidemiology of this heavily methylated
      subset of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 512-9.
      (c)2015 AACR.

PMID- 25587055
TI  - Degeneration and regeneration of corneal nerves in response to HSV-1 infection.
AB  - PURPOSE: Herpes simplex virus type 1 (HSV-1) infection is one cause of
      neurotrophic keratitis, characterized by decreases in corneal sensation, blink
      reflex, and tear secretion as consequence of damage to the sensory fibers
      innervating the cornea. Our aim was to characterize changes in the corneal nerve
      network and its function in response to HSV-1 infection. METHODS: C57BL/6J mice
      were infected with HSV-1 or left uninfected. Corneas were harvested at
      predetermined times post infection (pi) and assessed for beta III tubulin,
      substance P, calcitonin gene-related peptide, and neurofilament H staining by
      immunohistochemistry (IHC). Corneal sensitivity was evaluated using a Cochet
      Bonnet esthesiometer. Expression of genes associated with nerve repair was
      determined in corneas by real time RT-PCR, Western blotting, and IHC. Semaphorin
      7A (SEMA 7A) neutralizing antibody or isotype control was subconjunctivally
      administered to infected mice. RESULTS: The area of cornea occupied by beta III
      tubulin immunoreactivity and sensitivity significantly decreased by day 8 pi.
      Modified reinnervation was observed by day 30 pi without recovery of corneal
      sensation. Sensory fibers were lost by day 8 pi and were still absent or abnormal
      at day 30 pi. Expression of SEMA 7A increased at day 8 pi, localizing to corneal
      epithelial cells. Neutralization of SEMA 7A resulted in defective reinnervation
      and lower corneal sensitivity. CONCLUSIONS: Corneal sensory nerves were lost,
      consistent with loss of corneal sensation at day 8 pi. At day 30 pi, the cornea
      reinnervated but without recovering the normal arrangement of its fibers or
      function. SEMA 7A expression was increased at day 8pi, likely as part of a nerve
      regeneration mechanism.

PMID- 25587057
TI  - Papillomacular bundle and inner retinal thicknesses correlate with visual acuity
      in nonarteritic anterior ischemic optic neuropathy.
AB  - PURPOSE: To evaluate the ability of the papillomacular bundle (PMB) retinal nerve
      fiber layer and macular inner retinal layer thickness measurements with
      Spectralis optical coherence tomography (OCT) to differentiate eyes with
      nonarteritic anterior ischemic optic neuropathy (NAION) from uninvolved eyes and
      to evaluate whether their thicknesses correlate with visual acuity. METHODS: An
      observational, cross-sectional study was performed, including 29 eyes with NAION
      and 29 uninvolved eyes from 29 patients. Eyes underwent scanning with Cirrus OCT
      (peripapillary and macular scanning) and Spectralis OCT (N-site axonal
      peripapillary scan and a new automated segmentation macular scan to measure
      individual retinal layers) in both eyes. RESULTS: The NAION eyes showed
      significant thinning versus uninvolved eyes in the macular retinal nerve fiber (P
      < 0.05), ganglion cell layer (GCL; P < 0.001), and inner plexiform layer (IPL; P
      < 0.01) by Spectralis and in the GCL-IPL by Cirrus (P < 0.02). Average and
      sectors of peripapillary retinal nerve fiber layer (pRNFL) and total macular
      thickness (TMT) were significantly reduced in NAION eyes, with both Spectralis
      and Cirrus OCT (P < 0.05). Spectralis temporal (rhoSpearman = -0.768; P < 0.001)
      and PMB pRNFL thicknesses (rhoSpearman = -0.675; P < 0.001), as well as central
      macular IPL thickness (rhoSpearman = -0.735; P < 0.001), correlated strongly with
      best corrected visual acuity (BCVA). Quadratic regression using outer nasal TMT
      by Cirrus OCT and temporal pRNFL thickness by Spectralis were the best models to
      predict BCVA. CONCLUSIONS: Macular segmentation by Spectralis and Cirrus OCT
      revealed inner retinal layer atrophy in NAION eyes. The temporal and PMB pRNFL
      thicknesses and central macular IPL thickness by Spectralis-OCT and outer nasal
      TMT by Cirrus were strongly correlated with BCVA in NAION eyes.

PMID- 25587053
TI  - Progesterone action in breast, uterine, and ovarian cancers.
AB  - Progesterone and progesterone receptors (PRs) are essential for the development
      and cyclical regulation of hormone-responsive tissues including the breast and
      reproductive tract. Altered functions of PR isoforms contribute to the
      pathogenesis of tumors that arise in these tissues. In the breast, progesterone
      acts in concert with estrogen to promote proliferative and pro-survival gene
      programs. In sharp contrast, progesterone inhibits estrogen-driven growth in the
      uterus and protects the ovary from neoplastic transformation. Progesterone
      dependent actions and associated biology in diverse tissues and tumors are
      mediated by two PR isoforms, PR-A and PR-B. These isoforms are subject to altered
      transcriptional activity or expression levels, differential crosstalk with growth
      factor signaling pathways, and distinct post-translational modifications and
      cofactor-binding partners. Herein, we summarize and discuss the recent literature
      focused on progesterone and PR isoform-specific actions in breast, uterine, and
      ovarian cancers. Understanding the complexity of context-dependent PR actions in
      these tissues is critical to developing new models that will allow us to advance
      our knowledge base with the goal of revealing novel and efficacious therapeutic
      regimens for these hormone-responsive diseases.

PMID- 25587056
TI  - Adaptive optics microperimetry and OCT images show preserved function and
      recovery of cone visibility in macular telangiectasia type 2 retinal lesions.
AB  - PURPOSE: To evaluate visual function and disease progression in the retinal
      structural abnormalities of three patients from two unrelated families with
      macular telangiectasia (MacTel) type 2. METHODS: Adaptive optics scanning laser
      ophthalmoscopy (AOSLO) and AOSLO microperimetry (AOMP) were used to evaluate the
      structure and function of macular cones in three eyes with MacTel type 2. Cone
      spacing was estimated using histogram analysis of intercone distances, and
      registered spectral-domain optical coherence tomography (SD-OCT) scans were used
      to evaluate retinal anatomy. AOMP was used to assess visual sensitivity in and
      around areas of apparent cone loss. RESULTS: Although overall lesion surface area
      increased, some initially affected regions subsequently showed clear, contiguous,
      and normally spaced cone mosaics with recovered photoreceptor inner/outer segment
      (IS/OS) reflectivity (two of two eyes). The AOMP test sites fell within three
      categories: normal-appearing cones (N), dimly reflecting cones (D), and RPE cell
      mosaics (R). At N sites, AOMP threshold values (arbitrary units [au]) increased
      with increasing eccentricity (slope = 0.054 au/degree, r(2) = 0.77). The N
      thresholds ranged from 0.04 to 0.27 au, D thresholds from 0.04 to 0.33 au, and R
      thresholds from 0.14 to 1.00 au. There was measurable visual sensitivity
      everywhere except areas without intact external limiting membrane (ELM) and with
      diffuse scattering in the IS/OS and posterior tips of the outer segments (PTOS)
      regions on OCT. CONCLUSIONS: Visual sensitivity and recovery of cone visibility
      in areas of apparent focal cone loss suggests that MacTel type 2 lesions with a
      preserved ELM may contain functioning cones with abnormal scattering and/or
      waveguiding characteristics. (ClinicalTrials.gov number, NCT00254605.).

PMID- 25587058
TI  - Evaluation of 12 myopia-associated genes in Chinese patients with high myopia.
AB  - PURPOSE: Two recent large-scale genome-wide association studies identified
      significant associations between myopia and single nucleotide polymorphisms
      (SNPs) near the PRSS56, BMP3, KCNQ5, LAMA2, TOX, TJP2, RDH5, ZIC2, RASGRF1, GJD2,
      RBFOX1, and SHISA6 genes. Our study is to examine whether rare variants in these
      genes contribute to high myopia. METHODS: Whole-exome sequencing was performed on
      samples of 298 probands with early-onset high myopia (eoHM; spherical refraction
      in each meridian <= -6.00 [diopters] D in both eyes; age of onset < 7 years) and
      195 controls (different forms of retinal degeneration including Leber congenital
      amaurosis, cone-rod dystrophy, and familial exudative vitroretinopathy).
      Potential variations in these genes were selected for further validation and
      comparison to the controls. Moreover, Sanger sequencing was used to evaluate the
      coding regions and the upstream 800 bps of GJD2 in 395 additional subjects with
      late-onset moderate to high myopia (loMHM; spherical refraction in each meridian
      <= -4.00 D; age of onset >= 7 years) and 403 healthy controls (-0.50 D +/- 1.00
      D). RESULTS: Exome sequencing of the 298 probands with eoHM identified 25 rare
      variants that were predicted to affect coding residues. The segregation analysis
      and the distribution of rare variants between patients and controls did not
      provide evidence to support their involvement in myopia. Sanger sequencing of
      GJD2 in an additional 395 subjects with loMHM and 403 healthy controls did not
      identify myopia-associated variants. CONCLUSIONS: We did not find evidence to
      support the association of myopia with rare variants in these genes, probably due
      to our limited sample size. Additional studies are expected to validate these
      results.

PMID- 25587054
TI  - Genetic regulation of murine pituitary development.
AB  - Significant progress has been made recently in unravelling the embryonic events
      leading to pituitary morphogenesis, both in vivo and in vitro. This includes
      dissection of the molecular mechanisms controlling patterning of the ventral
      diencephalon that regulate formation of the pituitary anlagen or Rathke's pouch.
      There is also a better characterisation of processes that underlie maintenance of
      pituitary progenitors, specification of endocrine lineages and the three
      dimensional organisation of newly differentiated endocrine cells. Furthermore, a
      population of adult pituitary stem cells (SCs), originating from embryonic
      progenitors, have been described and shown to have not only regenerative
      potential, but also the capacity to induce tumour formation. Finally, the
      successful recapitulation in vitro of embryonic events leading to generation of
      endocrine cells from embryonic SCs, and their subsequent transplantation,
      represents exciting advances towards the use of regenerative medicine to treat
      endocrine deficits. In this review, an up-to-date description of pituitary
      morphogenesis will be provided and discussed with particular reference to
      pituitary SC studies.

PMID- 25587059
TI  - Choroidal thickness in geographic atrophy secondary to age-related macular
      degeneration.
AB  - PURPOSE: To analyze choroidal thickness (CT) in eyes with geographic atrophy (GA)
      secondary to age-related macular degeneration (AMD). METHODS: A total of 72 eyes
      of 72 patients (mean age, 75.97 +/- 7.09 years) with GA and 37 eyes of 37 healthy
      controls (73.89 +/- 6.19 years) were examined by confocal scanning laser
      ophthalmoscopy and enhanced depth imaging (EDI) spectral-domain optical coherence
      tomography. Choroidal thickness was measured at 25 defined points in horizontal
      and vertical scans. Geographic atrophy size was determined in fundus
      autofluorescence (FAF) images and GA subtypes were classified based on abnormal
      FAF in the perilesional zone. RESULTS: In GA, subfoveal CT (fCT) was
      significantly thinner compared to controls (173.03 +/- 90.22 vs. 253.95 +/- 69.19
      MUm, P < 0.001). Analysis of averaged measurements of all 25 points obtained per
      patient (mCT) revealed similar results (162.07 +/- 76.26 vs. 228.00 +/- 66.24
      MUm, P < 0.001). Spatial differences in CT between both groups were largest
      superior to the fovea. Addressing "diffuse-trickling" (n = 15) and "non-diffuse
      trickling" (n = 57) GA independently, fCT was 114.67 +/- 43.32 and 188.39 +/-
      93.26 MUm, respectively (P = 0.002), with both groups being significantly thinner
      than controls (P < 0.001 for "diffuse-trickling" and P < 0.001 for "?non-diffuse
      trickling"). Similar results were obtained for mCT, which was 110.21 +/- 29.66
      MUm in "diffuse-trickling," 175.72 +/- 79.02 MUm in "?non-diffuse-trickling" and
      228.00 +/- 66.24 MUm in controls. Differences were significant with P = 0.002
      between both GA groups and P <= 0.001 toward controls for each GA group.
      CONCLUSIONS: The results indicate that the choroid in eyes with GA is thinner
      compared to normal eyes of similar age. Hereby, the extent of thinning is most
      pronounced in a specific subtype of GA identified by FAF imaging ("diffuse
      trickling"). Such GA subtype-related differences in choroidal thickness may
      reflect heterogeneity in the pathogenesis of disease. (ClinicalTrials.gov number,
      NCT02051998.).

PMID- 25587061
TI  - An analysis of the factors influencing the residual refractive astigmatism after
      cataract surgery with toric intraocular lenses.
AB  - PURPOSE: To investigate the influence of posterior corneal astigmatism,
      surgically-induced corneal astigmatism (SICA), intraocular lens (IOL)
      orientation, and effective lens position on the refractive outcome of toric IOLs.
      METHODS: Five models were prospectively investigated. Keratometric astigmatism
      and an intended SICA of 0.2 diopters (D) were entered into model 1. Total corneal
      astigmatism, measured by a rotating Scheimpflug camera, was used instead of
      keratometric astigmatism in model 2. The mean postoperative SICA, the actual
      postoperative IOL orientation, and the influence of the effective lens position
      were added, respectively, into models 3, 4, and 5. Astigmatic data were
      vectorially described by meridional and torsional powers. A set of equations was
      developed to describe the error in refractive astigmatism (ERA) as the difference
      between the postoperative refractive astigmatism and the target refractive
      astigmatism. RESULTS: We enrolled 40 consecutive eyes. In model 1, ERA
      calculations revealed significant cylinder overcorrection in with-the-rule (WTR)
      eyes (meridional power = -0.59 +/- 0.34 D, P < 0.0001) and undercorrection in
      against-the-rule (ATR) eyes (0.32 +/- 0.42 D, P = 0.01). When total corneal
      astigmatism was used instead of keratometric astigmatism (model 2), the ERA
      meridional power decreased in WTR (-0.13 +/- 0.42 D) and ATR (0.07 +/- 0.59 D)
      eyes, both values being not statistically significant. Models 3 to 5 did not lead
      to significant improvement. CONCLUSIONS: Posterior corneal astigmatism exerts the
      highest influence on the ERA after toric IOL implantation. Basing calculations on
      total corneal astigmatism rather than keratometric astigmatism improves the
      prediction of the residual refractive astigmatism.

PMID- 25587060
TI  - Neuroprotective effects of transcription factor Brn3b in an ocular hypertension
      rat model of glaucoma.
AB  - PURPOSE: Glaucoma is an optic neuropathy commonly associated with elevated
      intraocular pressure (IOP), leading to optic nerve head (ONH) cupping, axon loss,
      and apoptosis of retinal ganglion cells (RGCs), which could ultimately result in
      blindness. Brn3b is a class-4 POU domain transcription factor that plays a key
      role in RGC development, axon outgrowth, and pathfinding. Previous studies
      suggest that a decrease in Brn3b levels occurs in animal models of glaucoma. The
      goal of this study was to determine if adeno-associated virus (AAV)-directed
      overexpression of the Brn3b protein could have neuroprotective effects following
      elevated IOP-mediated neurodegeneration. METHODS: Intraocular pressure was
      elevated in one eye of Brown Norway rats (Rattus norvegicus), following which the
      IOP-elevated eyes were intravitreally injected with AAV constructs encoding
      either the GFP (rAAV-CMV-GFP and rAAV-hsyn-GFP) or Brn3b (rAAV-CMV-Brn3b and rAAV
      hsyn-Brn3b). Retina sections through the ONH were stained for synaptic plasticity
      markers and neuroprotection was assessed by RGC counts and visual acuity tests.
      RESULTS: Adeno-associated virus-mediated expression of the Brn3b protein in IOP
      elevated rat eyes promoted an upregulation of growth associated protein-43 (GAP
      43), actin binding LIM protein (abLIM) and acetylated alpha-tubulin (ac-Tuba)
      both posterior to the ONH and in RGCs. The RGC survival as well as axon integrity
      score were significantly improved in IOP-elevated rAAV-hsyn-Brn3b-injected rats
      compared with those of the IOP-elevated rAAV-hsyn-GFP- injected rats.
      Additionally, intravitreal rAAV-hsyn-Brn3b administration significantly restored
      the visual optomotor response in IOP-elevated rat eyes. CONCLUSIONS: Adeno
      associated virus-mediated Brn3b protein expression may be a suitable approach for
      promoting neuroprotection in animal models of glaucoma.

PMID- 25587062
TI  - Evidence for lymphatics in the developing and adult human choroid.
AB  - PURPOSE: Lymphatics subserve many important functions in the human body including
      maintenance of fluid homeostasis, immune surveillance, and tumor metastasis. Our
      aim was to provide structural and phenotypic evidence of lymphatic-like
      structures in the human choroid, including details of its development. METHODS:
      Using multiple-marker immunohistochemistry (IHC), choroids from human fetal eyes
      (8-26 weeks gestation) and adults (17-74 years) were examined with lymphatic- and
      vascular-specific markers: prospero homeobox-1 (PROX-1), lymphatic vascular
      endothelium receptor-1 (LYVE-1), podoplanin, D2-40, endomucin, VEGF-C, vascular
      endothelial growth factor receptor-3 (VEGFR-3 or Flt4), UEA lectin, platelet
      endothelial cell adhesion molecule-1 (PECAM-1), CD34, and CD39. Transmission
      electron microscopy (TEM) was used to establish evidence for choroidal
      lymphatics, and to provide details of stratification and relative frequency of
      lymphatics compared to choroidal blood vessels. RESULTS: Immunohistochemistry and
      TEM indicated a central-to-peripheral topography of lymphatic formation, with
      numerous blind-ended lymph sacs just external to the choriocapillaris, as well as
      the presence of infrequent precollector and collector lymphatic channels.
      Characteristic ultrastructural features of lymphatics in adult human choroid
      included anchoring filaments, luminal flocculent protein but absence of
      erythrocytes, fragmented and/or absent basal lamina, absence of intracellular
      Weibel-Palade bodies, infrequent pericyte ensheathment, and lack of fenestrae.
      CONCLUSIONS: The system of blind-ended initial lymphatic segments seen just
      external to the fenestrated vessels of the choriocapillaris is ideally placed for
      recirculating extracellular fluid and strategically placed for immune
      surveillance. The presence of a system of lymphatic-like channels in the human
      choroid provides an anatomical basis for antigen presentation in the posterior
      eye, with a possible route from the eye to the sentinel lymph nodes, similar to
      that already described for anterior eye lymphatics.

PMID- 25587063
TI  - Delay in retinal photoreceptor development in very preterm compared to term
      infants.
AB  - PURPOSE: We compared photoreceptor development from spectral domain optical
      coherence tomography (SD-OCT) imaging in very preterm infants (VPT, <32 weeks
      gestational age) with those of term infants. METHODS: The microanatomy of foveal
      SD-OCT images obtained at the bedside at 37 to 42 weeks term equivalent
      postmenstrual age (TEA) was reviewed with qualitative and quantitative analysis
      of retinal and especially photoreceptor layers in the macula. Measures of
      maturity included presence of the cone outer segment tips (COST) or the ellipsoid
      zone (EZ) at foveal center, distance from Bruch's membrane (BM) to the EZ at the
      foveal center, and radial distance from foveal center to first appearance of the
      EZ. RESULTS: The incidence of the EZ developed at the foveal center was lower in
      VPT infants (9/64, 14%) versus term infants (22/47, 47%, P < 0.001) and lower in
      VPT infants with macular edema (3/46) versus VPT without edema (6/18, P = 0.01).
      Mean +/- SD distance from the foveal center to the visible EZ was 783 +/- 440 MUm
      in VPT, and 492 +/- 501 MUm in term infants, P = 0.002. The height of the BM-to
      EZ at the foveal center did not differ in VPT versus term infants. The COST band
      was not visible in any infant. CONCLUSIONS: Photoreceptor inner and outer segment
      development in VPT infants appears delayed when compared to term infants, and the
      photoreceptor RPE junction remains immature in all infants at TEA. Delayed
      maturation of photoreceptors could contribute to differences in visual function
      in some VPT infants.

PMID- 25587064
TI  - SeqHBase: a big data toolset for family based sequencing data analysis.
AB  - BACKGROUND: Whole-genome sequencing (WGS) and whole-exome sequencing (WES)
      technologies are increasingly used to identify disease-contributing mutations in
      human genomic studies. It can be a significant challenge to process such data,
      especially when a large family or cohort is sequenced. Our objective was to
      develop a big data toolset to efficiently manipulate genome-wide variants,
      functional annotations and coverage, together with conducting family based
      sequencing data analysis. METHODS: Hadoop is a framework for reliable, scalable,
      distributed processing of large data sets using MapReduce programming models.
      Based on Hadoop and HBase, we developed SeqHBase, a big data-based toolset for
      analysing family based sequencing data to detect de novo, inherited homozygous,
      or compound heterozygous mutations that may contribute to disease manifestations.
      SeqHBase takes as input BAM files (for coverage at every site), variant call
      format (VCF) files (for variant calls) and functional annotations (for variant
      prioritisation). RESULTS: We applied SeqHBase to a 5-member nuclear family and a
      10-member 3-generation family with WGS data, as well as a 4-member nuclear family
      with WES data. Analysis times were almost linearly scalable with number of data
      nodes. With 20 data nodes, SeqHBase took about 5 secs to analyse WES familial
      data and approximately 1 min to analyse WGS familial data. CONCLUSIONS: These
      results demonstrate SeqHBase's high efficiency and scalability, which is
      necessary as WGS and WES are rapidly becoming standard methods to study the
      genetics of familial disorders.

PMID- 25587066
TI  - Long working hours are linked to risky alcohol consumption.

PMID- 25587067
TI  - GPs rarely use interventions for weight management in obese and overweight
      patients, study finds.

PMID- 25587065
TI  - Long working hours and alcohol use: systematic review and meta-analysis of
      published studies and unpublished individual participant data.
AB  - OBJECTIVE: To quantify the association between long working hours and alcohol
      use. DESIGN: Systematic review and meta-analysis of published studies and
      unpublished individual participant data. DATA SOURCES: A systematic search of
      PubMed and Embase databases in April 2014 for published studies, supplemented
      with manual searches. Unpublished individual participant data were obtained from
      27 additional studies. REVIEW METHODS: The search strategy was designed to
      retrieve cross sectional and prospective studies of the association between long
      working hours and alcohol use. Summary estimates were obtained with random
      effects meta-analysis. Sources of heterogeneity were examined with meta
      regression. RESULTS: Cross sectional analysis was based on 61 studies
      representing 333,693 participants from 14 countries. Prospective analysis was
      based on 20 studies representing 100,602 participants from nine countries. The
      pooled maximum adjusted odds ratio for the association between long working hours
      and alcohol use was 1.11 (95% confidence interval 1.05 to 1.18) in the cross
      sectional analysis of published and unpublished data. Odds ratio of new onset
      risky alcohol use was 1.12 (1.04 to 1.20) in the analysis of prospective
      published and unpublished data. In the 18 studies with individual participant
      data it was possible to assess the European Union Working Time Directive, which
      recommends an upper limit of 48 hours a week. Odds ratios of new onset risky
      alcohol use for those working 49-54 hours and >= 55 hours a week were 1.13 (1.02
      to 1.26; adjusted difference in incidence 0.8 percentage points) and 1.12 (1.01
      to 1.25; adjusted difference in incidence 0.7 percentage points), respectively,
      compared with working standard 35-40 hours (incidence of new onset risky alcohol
      use 6.2%). There was no difference in these associations between men and women or
      by age or socioeconomic groups, geographical regions, sample type (population
      based v occupational cohort), prevalence of risky alcohol use in the cohort, or
      sample attrition rate. CONCLUSIONS: Individuals whose working hours exceed
      standard recommendations are more likely to increase their alcohol use to levels
      that pose a health risk.

PMID- 25587069
TI  - Epigenetic Changes Induced by Hypoxia-Inducible Factor: a Long Way Still To Go as
      a Target for Therapy?

PMID- 25587070
TI  - US court cannot force tobacco companies to say they are "unscrupulous villains,"
      claims industry appeal.

PMID- 25587071
TI  - Impact commentaries. Subacute necrotising encephalomyelopathy (Leigh's disease;
      Leigh syndrome).

PMID- 25587068
TI  - MicroRNA-687 Induced by Hypoxia-Inducible Factor-1 Targets Phosphatase and Tensin
      Homolog in Renal Ischemia-Reperfusion Injury.
AB  - Ischemia-reperfusion injury contributes to tissue damage and organ failure in
      clinical settings, but the underlying mechanism remains elusive and effective
      therapies are still lacking. Here, we identified microRNA 687 (miR-687) as a key
      regulator and therapeutic target in renal ischemia-reperfusion injury. We show
      that miR-687 is markedly upregulated in the kidney during renal ischemia
      reperfusion in mice and in cultured kidney cells during hypoxia. MiR-687
      induction under these conditions was mediated by hypoxia-inducible factor-1 (HIF
      1). Upon induction in vitro, miR-687 repressed the expression of phosphatase and
      tensin homolog (PTEN) and facilitated cell cycle progression and apoptosis.
      Blockade of miR-687 preserved PTEN expression and attenuated cell cycle
      activation and renal apoptosis, resulting in protection against kidney injury in
      mice. Collectively, these results unveil a novel HIF-1/miR-687/PTEN signaling
      pathway in ischemia-reperfusion injury that may be targeted for therapy. 

PMID- 25587072
TI  - Lateralising value of experiential hallucinations in temporal lobe epilepsy.
AB  - OBJECTIVES: Ever since John Hughlings Jackson first described the so-called
      'dreamy state' during temporal lobe epilepsy, that is, the sense of an abnormal
      familiarity (deja vu) or vivid memory-like hallucinations from the past
      (experiential hallucinations), these phenomena have been studied and repeatedly
      linked to mesial temporal lobe structures. However, little is known about the
      lateralising value of either deja vu or experiential hallucinations. METHODS: We
      analysed a sample of 28 patients with intractable focal epilepsy suffering from
      either deja vu or experiential hallucinations. All the patients underwent
      thorough presurgical examination, including MRI, positron emission tomography,
      single-photon emission CT, EEG and neuropsychological examination. RESULTS: While
      deja vu was due to right or left mesial temporal lobe epilepsy, experiential
      hallucinations were strongly lateralised to the left mesial temporal lobe.
      Moreover, there was a significant effect for interictal language deficits being
      more frequent in patients suffering from experiential hallucinations.
      CONCLUSIONS: These results suggest a lateralising value for experiential
      hallucinations to the left temporal lobe.

PMID- 25587074
TI  - Modified 16S-23S rRNA intergenic region restriction endonuclease analysis for
      species identification of Enterococcus strains isolated from pigs, compared with
      identification using classical methods and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Fast and reliable identification of bacteria to at least the species level is
      currently the basis for correct diagnosis and appropriate treatment of
      infections. This is particularly important in the case of bacteria of the genus
      Enterococcus, whose resistance profile is often correlated with their species
      (e.g. resistance to vancomycin). In this study, we evaluated restriction
      endonuclease analysis of the 16S-23S rRNA gene intergenic transcribed spacer
      (ITS) region for species identification of Enterococcus. The utility of the
      method was compared with that of phenotypic methods [biochemical profile
      evaluation and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS)]. Identification was based on 21 Enterococcus
      reference strains, of the species E. faecalis, E. faecium, E. hirae, E. durans,
      E. casseliflavus, E. gallinarum, E. avium, E. cecorum and E. columbae, and 47
      Enterococcus field strains isolated from pigs. Restriction endonuclease analysis
      of the ITS-PCR product using HinfI, RsaI and MboI, in the order specified,
      enabled species differentiation of the Enterococcus reference and field strains,
      and in the case of the latter, the results of species identification were
      identical (47/47) to those obtained by MALDI-TOF MS. Moreover, as a result of
      digestion with MboI, a unique restriction profile was also obtained for the
      strains (3/3) identified by MALDI-TOF MS as E. thailandicus. In our opinion,
      restriction endonuclease analysis of the 16S-23S rRNA gene ITS region of
      Enterococcus may be a simple and relatively fast (less than 4 h) alternative
      method for identifying the species occurring most frequently in humans and
      animals. 

PMID- 25587080
TI  - Faecal levels of zonula occludens toxin in paediatric patients with Crohn's
      disease and their association with the intestinal microbiota.

PMID- 25587073
TI  - Comparison of turnaround time and time to oseltamivir discontinuation between two
      respiratory viral panel testing methodologies.

PMID- 25587081
TI  - High prevalence of Escherichia coli sequence type 131 among antimicrobial
      resistant E. coli isolates from geriatric patients.
AB  - Previous work on the subclones within Escherichia coli ST131 predominantly
      involved isolates from Western countries. This study assessed the prevalence and
      antimicrobial resistance attributed to this clonal group. A total of 340
      consecutive, non-duplicated urinary E. coli isolates originating from four
      clinical laboratories in Hong Kong in 2013 were tested. ST131 prevalence among
      the total isolates was 18.5 % (63/340) and was higher among inpatient isolates
      (23.0 %) than outpatient isolates (11.8 %, P<0.001), and higher among isolates
      from patients aged >=65 years than from patients aged 18-50 years and 51-64 years
      (25.4 vs 3.4 and 4.0 %, respectively, P<0.001). Of the 63 ST131 isolates, 43
      (68.3 %) isolates belonged to the H30 subclone, whereas the remaining isolates
      belonged to H41 (n = 17), H54 (n = 2) and H22 (n = 1). All H30 isolates were
      ciprofloxacin-resistant, of which 18.6 % (8/43) belonged to the H30-Rx subclone.
      Twenty-six (41.3 %) ST131 isolates were ESBL-producers, of which 19 had blaCTX-M
      14 (12 non-H30-Rx, two H30-Rx and five H41), six had blaCTX-M-15 (five non-H30-Rx
      and one H30-Rx) and one was blaCTX-M-negative (H30). In conclusion, ST131
      accounts for a large share of the antimicrobial-resistant E. coli isolates from
      geriatric patients. Unlike previous reports, ESBL-producing ST131 strains mainly
      belonged to non-H30-Rx rather than the H30-Rx subclone, with blaCTX-M-14 as the
      dominant enzyme type. 

PMID- 25587082
TI  - Phenotypic and molecular characterization of Malassezia japonica isolated from
      psoriasis vulgaris patients.
AB  - Malassezia species, which are skin colonizers, are being debated as to their
      pathogenic role in various cutaneous diseases. Species identification of
      Malassezia is important as particular species have been implicated in or
      associated with specific diseases. Malassezia japonica, a relatively newly
      described species, has not been completely characterized owing to the rarity of
      its isolation. In the present study we describe phenotypic and molecular
      characterization of six M. japonica strains isolated from patients with psoriasis
      vulgaris. In contrast to the physiological and biochemical properties of the M.
      japonica type strain, CBS9348, all our isolates assimilated Tween 20 and showed
      positive beta-glucosidase activity, and the Cremophor EL utilization test was
      negative. However, the sequences of the D1/D2 region of rDNA, ITS2 and IGS1
      regions of all our isolates clustered with the type strain of M. japonica. 

PMID- 25587083
TI  - Multiplex assay (Mikrogen recomBead) for detection of serum IgG and IgM
      antibodies to 13 recombinant antigens of Borrelia burgdorferi sensu lato in
      patients with neuroborreliosis: the more the better?
AB  - A multiplex-bead-based assay for the detection of serum antibodies to Borrelia
      burgdorferi sensu lato was evaluated. The assay contained 13 different antigens
      in both the IgG and the IgM assay; thus, a total of 26 measurement results were
      available from each sample. A total of 49 Danish patients with Lyme
      neuroborreliosis (LNB), 218 Danish blood donor controls, a set of 61 Swedish
      patients with LNB and 139 Swedish non-LNB patients investigated for suspected LNB
      were used. There are four parts developed in this study: a characterization of
      the sero-epidemiological antibody-response pattern, the construction of a
      diagnostic score, evaluation of the scoring method using an independent dataset
      and an assessment of the analytical quality of the multiplex assay. The VlsE IgG
      had the highest diagnostic value with an AUC (area under the curve) of 96% on the
      receiver operating characteristic curve. The OspC IgM had AUCs just above 80%.
      All the other antigens had both low quantitative reactivity and lower contrast in
      the patients with LNB compared to controls. The diagnostic value of the assay may
      be improved by using a logistic model giving a sensitivity of 90 and 79% for the
      specificities at 92 and 98%, respectively. Overall, the patients with LNB had
      serum reactivity in IgG VlsE, but modest antibody reactivity in the remaining 12
      IgG and 13 IgM antibody measurements. Using a logistic regression model with five
      IgG and two IgM antigens, the sensitivity and specificity of the assay was
      improved; but the IgG VlsE component alone contributed most of the diagnostic
      contrast. 

PMID- 25587084
TI  - A prospective study of mucormycosis in north India: experience from a tertiary
      care hospital.
AB  - Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous
      filamentous fungi of the Order Mucorales and class of Mucormycetes. We conducted
      a prospective study of 38 patients who were diagnosed as having mucormycosis in a
      tertiary care hospital during January 2010 to June 2011. The cases were analyzed
      regarding the site of involvement, underlying disease and species of fungi
      isolated, antifungal susceptibility pattern of the isolates, and outcome of
      therapy. The mean age of the patients was 40.43 years, with 72% male. Rhino
      orbital mucormycosis (61.5%) was the most common presentation followed by
      cutaneous manifestations (31%), gastrointestinal symptoms (5%), and pulmonary
      (2.5%). Diabetes mellitus (56%) was the significant risk factor in rhino-orbito
      cerebral presentation (OR = 7.55, P = 0.001). Among 23 culture isolates, Rhizopus
      arrhizus (37.5%) was the most common, followed by Apophysomyces variabilis
      (29.2%), Lichtheimia ramosa (16.7%), Rhizopus microsporus (4.2%), Rhizomucor
      pusillus (4.2%), and Apophysomyces elegans (4.2%). Rhizopus arrhizus was most
      commonly isolated from rhino-orbito-cerebral mucormycosis and Apophysomyces
      species were generally obtained from cutaneous mucormycosis. In vitro antifungal
      susceptibility showed that 16 isolates were sensitive to amphotericin B (MIC less
      than 1 MUg/ml), while in contrast, all isolates were found to be resistant to
      voriconazole (MIC- 0.25 to >8), fluconazole (MIC > 32), flucytosine (MIC > 32).
      Treatment regimens included antifungal therapy, reversal of underlying
      predisposing risk factors, and surgical debridement. Combination of surgery and
      medical treatment with amphotericin B was significantly better (OR = 0.2, P <
      0.04) than amphotericin B alone (61.5% vs. 10.3% patient survival). The awareness
      of fungal diseases amongst clinicians is required to decrease the fatal outcome
      of disease. 

PMID- 25587086
TI  - Photo quiz. Breast mass in a 45-year-old man.

PMID- 25587089
TI  - Should proton pump inhibitors be withheld from patients taking clopidogrel? The
      issue that has been giving me heartburn!

PMID- 25587085
TI  - LEF1 Targeting EMT in Prostate Cancer Invasion Is Regulated by miR-34a.
AB  - The microRNA-34a (miR-34a), a tumor-suppressive microRNA (miRNA), is implicated
      in epithelial-mesenchymal transition (EMT) and cancer stem cells. Lymphoid
      enhancer-binding factor-1 (LEF1) is a key transcription factor in the Wnt
      signaling pathway, and has been suggested to be involved in regulation of cell
      proliferation and invasion. Here, the molecular mechanism of miR-34a and LEF1 in
      cooperatively regulating prostate cancer cell invasion is described. Molecular
      profiling analysis of miRNA levels in prostate cancer cells revealed a negative
      correlation between miR-34a and LEF1 expression, and the downregulation of LEF1
      by miR-34a was confirmed by luciferase assays. Furthermore, miR-34a specifically
      repressed LEF1 expression through direct binding to its 3'-untranslated regions
      (3'-UTR). miR-34a modulated the levels of LEF1 to regulate EMT in prostate cancer
      cells. Functionally, miR-34a negatively correlated with the migration and
      invasion of prostate cancer cells through LEF1. An analysis of miR-34a expression
      levels in matched human tumor and benign tissues demonstrated consistent and
      statistically significant downregulation of miR-34a in primary prostate cancer
      specimens. These data strongly suggest that miR-34a/LEF1 regulation of EMT plays
      an important role in prostate cancer migration and invasion. IMPLICATIONS: The
      miR-34a-LEF1 axis represents a potential molecular target for novel therapeutic
      strategies in prostate cancer.

PMID- 25587088
TI  - Interventions to reduce dependency in personal activities of daily living in
      community dwelling adults who use homecare services: a systematic review.
AB  - OBJECTIVES: To identify interventions that aim to reduce dependency in activities
      of daily living (ADL) in homecare service users. To determine: content;
      effectiveness in improving ability to perform ADL; and whether delivery by
      qualified occupational therapists influences effectiveness. DATA SOURCES: The
      Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, CINAHL,
      PsycINFO, OTseeker, PEDro, Web of Science, CIRRIE, and ASSIA. REVIEW METHODS: We
      included: randomised controlled trials, non-randomised controlled trials and
      controlled before and after studies. Two reviewers independently screened studies
      for inclusion, assessed risk of bias and extracted data. A narrative synthesis of
      the findings was conducted. RESULTS: Thirteen studies were included, totalling
      4975 participants. Ten (77%) were judged to have risk of bias. Interventions were
      categorised as those termed 're-ablement' or 'restorative homecare' (n=5/13); and
      those involving separate components which were not described using this
      terminology (n=8/13). Content of the intervention and level of health
      professional input varied within and between studies. Effectiveness on ADL: eight
      studies included an ADL outcome, five favoured the intervention group, only two
      with statistical significance, both these were controlled before and after
      studies judged at high risk of bias. ADL outcome was reported using seven
      different measures. Occupational therapy: there was insufficient evidence to
      determine whether involvement of qualified occupational therapists influenced
      effectiveness. CONCLUSION: There is limited evidence that interventions targeted
      at personal ADL can reduce homecare service users' dependency with activities,
      the content of evaluated interventions varies greatly.

PMID- 25587090
TI  - Effect of a computer-guided, quality improvement program for cardiovascular
      disease risk management in primary health care: the treatment of cardiovascular
      risk using electronic decision support cluster-randomized trial.
AB  - BACKGROUND: Despite effective treatments to reduce cardiovascular disease risk,
      their translation into practice is limited. METHODS AND RESULTS: Using a parallel
      arm cluster-randomized controlled trial in 60 Australian primary healthcare
      centers, we tested whether a multifaceted quality improvement intervention
      comprising computerized decision support, audit/feedback tools, and staff
      training improved (1) guideline-indicated risk factor measurements and (2)
      guideline-indicated medications for those at high cardiovascular disease risk.
      Centers had to use a compatible software system, and eligible patients were
      regular attendees (Aboriginal and Torres Strait Islander people aged >= 35 years
      and others aged >= 45 years). Patient-level analyses were conducted using
      generalized estimating equations to account for clustering. Median follow-up for
      38,725 patients (mean age, 61.0 years; 42% men) was 17.5 months. Mean monthly
      staff support was <1 hour/site. For the coprimary outcomes, the intervention was
      associated with improved overall risk factor measurements (62.8% versus 53.4%
      risk ratio; 1.25; 95% confidence interval, 1.04-1.50; P=0.02), but there was no
      significant differences in recommended prescriptions for the high-risk cohort
      (n=10,308; 56.8% versus 51.2%; P=0.12). There were significant treatment
      escalations (new prescriptions or increased numbers of medicines) for
      antiplatelet (17.9% versus 2.7%; P<0.001), lipid-lowering (19.2% versus 4.8%;
      P<0.001), and blood pressure-lowering medications (23.3% versus 12.1%; P=0.02).
      CONCLUSIONS: In Australian primary healthcare settings, a computer-guided quality
      improvement intervention, requiring minimal support, improved cardiovascular
      disease risk measurement but did not increase prescription rates in the high-risk
      group. Computerized quality improvement tools offer an important, albeit partial,
      solution to improving primary healthcare system capacity for cardiovascular
      disease risk management. CLINICAL TRIAL REGISTRATION URL:
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=336630.
      Australian New Zealand Clinical Trials Registry No. 12611000478910.

PMID- 25587092
TI  - Association of discharge summary quality with readmission risk for patients
      hospitalized with heart failure exacerbation.

PMID- 25587091
TI  - Hospital variation in quality of discharge summaries for patients hospitalized
      with heart failure exacerbation.
AB  - BACKGROUND: Single-site studies have demonstrated inadequate quality of discharge
      summaries in timeliness, transmission, and content, potentially contributing to
      adverse outcomes. However, degree of hospital-level variation in discharge
      summary quality for patients hospitalized with heart failure (HF) is uncertain.
      METHODS AND RESULTS: We analyzed discharge summaries of patients enrolled in the
      Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) study. We assessed
      hospital-level performance on timeliness (fraction of summaries completed on the
      day of discharge), documented transmission to the follow-up physician, and
      content (presence of components suggested by the Transitions of Care Consensus
      Conference). We obtained 1501 discharge summaries from 1640 (91.5%) patients
      discharged alive from 46 hospitals. Among hospitals contributing >= 10 summaries,
      the median hospital dictated 69.2% of discharge summaries on the day of discharge
      (range, 0.0%-98.0%; P<0.001); documented transmission of 33.3% of summaries to
      the follow-up physician (range, 0.0%-75.7%; P<0.001); and included 3.6 of 7
      Transitions of Care Consensus Conference elements (range, 2.9-4.5; P<0.001).
      Hospital course was typically included (97.2%), but summaries were less likely to
      include discharge condition (30.7%), discharge volume status (16.0%), or
      discharge weight (15.7%). No discharge summary included all 7 Transitions of Care
      Consensus Conference-endorsed content elements, was dictated on the day of
      discharge, and was sent to a follow-up physician. CONCLUSIONS: Even at the
      highest performing hospital, discharge summary quality is insufficient in terms
      of timeliness, transmission, and content. Improvements in all aspects of
      discharge summary quality are necessary to enable the discharge summary to serve
      as an effective transitional care tool.

PMID- 25587093
TI  - Validity of international classification of disease codes to identify ischemic
      stroke and intracranial hemorrhage among individuals with associated diagnosis of
      atrial fibrillation.
AB  - BACKGROUND: Because of its association with death and disability, stroke is a
      focus of outcomes in atrial fibrillation (AF) research. International
      Classification of Disease-Ninth Revision (ICD-9) edition codes are commonly used
      to identify stroke in research, particularly in large administrative data. We
      sought to assess the validity of ICD-9 codes in stroke case ascertainment and for
      AF across 3 institutions. METHODS AND RESULTS: Participating centers included
      Boston Medical Center (safety net hospital), Geisinger Health System (rural
      Pennsylvania), and the University of Alabama (academic center in the southeastern
      stroke belt). ICD-9 codes for ischemic stroke (433-434, 436) and intracranial
      hemorrhage (430-432) identified 1812 stroke cases with an associated code for AF
      (427.31) from 2006 to 2010. Cases were vetted through chart review with final
      adjudication by a stroke neurologist. Review considered 94.2% of ICD-9 identified
      stroke cases valid with decreased accuracy for concurrent AF diagnosis (82.28%)
      and stroke attributable to AF (72.8%). Among events with "without infarction"
      modifiers, 7.2% were valid strokes. ICD-9 stroke code accuracy did not differ by
      stroke type or site. Stroke code 434 displayed higher accuracy than 433 (94.4%
      versus 85.2%; P<0.01), and primary stroke codes were more accurate than
      nonprimary codes (97.2% versus 83.7%; P<0.0001). CONCLUSIONS: Using ICD-9 stroke
      and AF codes to identify patients with stroke plus AF resulted in inaccuracies.
      Given the expanded financial and policy implications of patient-oriented
      research, conclusions derived solely from administrative data without validation
      of outcome events should be interpreted with caution.

PMID- 25587095
TI  - Age-specific performance of the revised cardiac risk index for predicting
      cardiovascular risk in elective noncardiac surgery.
AB  - BACKGROUND: The revised cardiac risk index (RCRI) holds a central role in
      preoperative cardiac risk stratification in noncardiac surgery. Its performance
      in unselected populations, including different age groups, has, however, not been
      systematically investigated. We assessed the relationship of RCRI with major
      adverse cardiovascular events in an unselected cohort of patients undergoing
      elective, noncardiac surgery overall and in different age groups. METHODS AND
      RESULTS: We followed up all individuals >= 25 years who underwent major elective
      noncardiac surgery in Denmark (January 1, 2005, to November 30, 2011) for the 30
      day risk of major adverse cardiovascular events (ischemic stroke, myocardial
      infarction, or cardiovascular death). There were 742 of 357,396 (0.2%), 755 of
      74.889 (1.0%), 521 of 11,921 (4%), and 257 of 3146 (8%) major adverse
      cardiovascular events occurring in RCRI classes I, II, III, and IV. Multivariable
      odds ratio estimates were as follows: ischemic heart disease 3.30 (95% confidence
      interval, 2.96-3.69), high-risk surgery 2.70 (2.46-2.96), congestive heart
      failure 2.65 (2.29-3.06), cerebrovascular disease 10.02 (9.08-11.05), insulin
      therapy 1.62 (1.37-1.93), and kidney disease 1.45 (1.33-1.59). Modeling RCRI
      classes as a continuous variable, C statistic was highest among age group 56 to
      65 years (0.772) and lowest for those aged >85 years (0.683). Sensitivity of RCRI
      class >I (ie, having >= 1 risk factor) for capturing major adverse cardiovascular
      events was 59%, 71%, 64%, 66%, and 67% in patients aged <= 55, 56 to 65, 66 to
      75, 76 to 85, and >85 years, respectively; the negative predictive values were
      >98% across all age groups. CONCLUSIONS: In a nationwide unselected cohort, the
      performance of the RCRI was similar to that of the original cohort. Having >= 1
      risk factor was of moderate sensitivity, but high negative predictive value for
      all ages.

PMID- 25587094
TI  - Conflicting results between randomized trials and observational studies on the
      impact of proton pump inhibitors on cardiovascular events when coadministered
      with dual antiplatelet therapy: systematic review.
AB  - BACKGROUND: Discordant results have been reported on the effects of concomitant
      use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for
      cardiovascular outcomes. We conducted a systematic review comparing the
      effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge
      treatment of unstable angina/non-ST-segment-elevation myocardial infarction
      patients. METHODS AND RESULTS: We searched for clinical studies in MEDLINE,
      EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012.
      Reviewers screened and extracted data, assessed applicability and quality, and
      graded the strength of evidence. We performed meta-analyses of direct comparisons
      when outcomes and follow-up periods were comparable. Thirty-five studies were
      eligible. Five (4 randomized controlled trials and 1 observational) assessed the
      effect of omeprazole when added to DAPT; the other 30 (observational) assessed
      the effect of PPIs as a class when compared with no PPIs. Random-effects meta
      analyses of the studies assessing PPIs as a class consistently reported higher
      event rates in patients receiving PPIs for various clinical outcomes at 1 year
      (composite ischemic end points, all-cause mortality, nonfatal MI, stroke,
      revascularization, and stent thrombosis). However, the results from randomized
      controlled trials evaluating omeprazole compared with placebo showed no
      difference in ischemic outcomes, despite a reduction in upper gastrointestinal
      bleeding with omeprazole. CONCLUSIONS: Large, well-conducted observational
      studies of PPIs and randomized controlled trials of omeprazole seem to provide
      conflicting results for the effect of PPIs on cardiovascular outcomes when
      coadministered with DAPT. Prospective trials that directly compare
      pharmacodynamic parameters and clinical events among specific PPI agents in
      patients with unstable angina/non-ST-segment-elevation myocardial infarction
      treated with DAPT are warranted.

PMID- 25587096
TI  - Cellular postconditioning: allogeneic cardiosphere-derived cells reduce infarct
      size and attenuate microvascular obstruction when administered after reperfusion
      in pigs with acute myocardial infarction.
AB  - BACKGROUND: Intracoronary delivery of cardiosphere-derived cells (CDCs) has been
      demonstrated to be safe and effective in porcine and human chronic myocardial
      infarction. However, intracoronary delivery of CDCs after reperfusion in acute
      myocardial infarction has never been assessed in a clinically-relevant large
      animal model. We tested CDCs as adjunctive therapy to reperfusion in a porcine
      model of myocardial infarction. METHODS AND RESULTS: First, escalating doses (5,
      7.5, and 10 million cells) of allogeneic CDCs were administered intracoronary 30
      minutes after reperfusion. Forty-eight hours later, left ventriculography was
      performed and animals euthanized to measure area at risk, infarct size (IS), and
      microvascular obstruction. Second, identical end points were measured in a
      pivotal study of minipigs (n=14) that received 8.5 to 9 million allogeneic CDCs,
      placebo solution, or sham. Multiple indicators of cardioprotection were observed
      with 7.5 and 10 million allogeneic CDCs, but not 5 million CDCs, relative to
      control. In the pivotal study, IS, microvascular obstruction, cardiomyocyte
      apoptosis, and adverse left ventricular remodeling were all smaller in the CDC
      group than in sham or placebo groups. In addition, serum troponin I level at 24
      hours was lower after CDC infusion than that in the placebo or sham groups,
      consistent with the histologically-demonstrated reduction in IS. CONCLUSIONS:
      Intracoronary delivery of allogeneic CDCs is safe, feasible, and effective in
      cardioprotection, reducing IS, preventing microvascular obstruction, and
      attenuating adverse acute remodeling. This novel cardioprotective effect, which
      we call cellular postconditioning, differs from previous strategies to reduce IS
      in that it works even when initiated with significant delay after reflow.

PMID- 25587098
TI  - lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing
      endogenous RNA.
AB  - RATIONALE: Pathological angiogenesis is a critical component of diseases, such as
      ocular disorders, cancers, and atherosclerosis. It is usually caused by the
      abnormal activity of biological processes, such as cell proliferation, cell
      motility, immune, or inflammation response. Long noncoding RNAs (lncRNAs) have
      emerged as critical regulators of these biological processes. However, the role
      of lncRNA in diabetes mellitus-induced microvascular dysfunction is largely
      unknown. OBJECTIVE: To elucidate whether lncRNA-myocardial infarction-associated
      transcript (MIAT) is involved in diabetes mellitus-induced microvascular
      dysfunction. METHODS AND RESULTS: Using quantitative polymerase chain reaction,
      we demonstrated increased expression of lncRNA-MIAT in diabetic retinas and
      endothelial cells cultured in high glucose medium. Visual electrophysiology
      examination, TUNEL staining, retinal trypsin digestion, vascular permeability
      assay, and in vitro studies revealed that MIAT knockdown obviously ameliorated
      diabetes mellitus-induced retinal microvascular dysfunction in vivo, and
      inhibited endothelial cell proliferation, migration, and tube formation in vitro.
      Bioinformatics analysis, luciferase assay, RNA immunoprecipitation, and in vitro
      studies revealed that MIAT functioned as a competing endogenous RNA, and formed a
      feedback loop with vascular endothelial growth factor and miR-150-5p to regulate
      endothelial cell function. CONCLUSIONS: This study highlights the involvement of
      lncRNA-MIAT in pathological angiogenesis and facilitates the development of
      lncRNA-directed diagnostics and therapeutics against neovascular diseases.

PMID- 25587097
TI  - Endocardial fibroelastosis is caused by aberrant endothelial to mesenchymal
      transition.
AB  - RATIONALE: Endocardial fibroelastosis (EFE) is a unique form of fibrosis, which
      forms a de novo subendocardial tissue layer encapsulating the myocardium and
      stunting its growth, and which is typically associated with congenital heart
      diseases of heterogeneous origin, such as hypoplastic left heart syndrome.
      Relevance of EFE was only recently highlighted through the establishment of
      staged biventricular repair surgery in infant patients with hypoplastic left
      heart syndrome, where surgical removal of EFE tissue has resulted in improvement
      in the restrictive physiology leading to the growth of the left ventricle in
      parallel with somatic growth. However, pathomechanisms underlying EFE formation
      are still scarce, and specific therapeutic targets are not yet known. OBJECTIVE:
      Here, we aimed to investigate the cellular origins of EFE tissue and to gain
      insights into the underlying molecular mechanisms to ultimately develop novel
      therapeutic strategies. METHODS AND RESULTS: By utilizing a novel EFE model of
      heterotopic transplantation of hearts from newborn reporter mice and by analyzing
      human EFE tissue, we demonstrate for the first time that fibrogenic cells within
      EFE tissue originate from endocardial endothelial cells via aberrant endothelial
      to mesenchymal transition. We further demonstrate that such aberrant endothelial
      to mesenchymal transition involving endocardial endothelial cells is caused by
      dysregulated transforming growth factor beta/bone morphogenetic proteins
      signaling and that this imbalance is at least in part caused by aberrant promoter
      methylation and subsequent transcriptional suppression of bone morphogenetic
      proteins 5 and 7. Finally, we provide evidence that supplementation of exogenous
      recombinant bone morphogenetic proteins 7 effectively ameliorates endothelial to
      mesenchymal transition and experimental EFE in rats. CONCLUSIONS: In summary, our
      data point to aberrant endothelial to mesenchymal transition as a common
      denominator of infant EFE development in heterogeneous, congenital heart
      diseases, and to bone morphogenetic proteins 7 as an effective treatment for EFE
      and its restriction of heart growth.

PMID- 25587099
TI  - Predicting graft loss by 1 year in pediatric heart transplantation candidates: an
      analysis of the Pediatric Heart Transplant Study database.
AB  - BACKGROUND: Pediatric data on the impact of pre-heart transplantation (HTx) risk
      factors on early post-HTx outcomes remain inconclusive. Thus, among patients with
      previous congenital heart disease or cardiomyopathy, disease-specific risk models
      for graft loss were developed with the use pre-HTx recipient and donor
      characteristics. METHODS AND RESULTS: Patients enrolled in the Pediatric Heart
      Transplant Study (PHTS) from 1996 to 2006 were stratified by pre-HTx diagnosis
      into cardiomyopathy and congenital heart disease cohorts. Logistic regression
      identified independent, pre-HTx risk factors. Risk models were constructed for 1
      year post-HTx graft loss. Donor factors were added for model refinement. The
      models were validated with the use of patients transplanted from 2007 to 2009.
      Risk factors for graft loss were identified in patients with cardiomyopathy
      (n=896) and congenital heart disease (n=965). For cardiomyopathy, independent
      risk factors were earlier year of transplantation, nonwhite race, female sex,
      diagnosis other than dilated cardiomyopathy, higher blood urea nitrogen, and
      panel reactive antibody >10%. The recipient characteristic risk model had good
      accuracy in the validation cohort, with predicted versus actual survival of 97.5%
      versus 95.3% (C statistic, 0.73). For patients with congenital heart disease,
      independent risk factors were nonwhite race, history of Fontan, ventilator
      dependence, higher blood urea nitrogen, panel reactive antibody >10%, and lower
      body surface area. The risk model was less accurate, with 86.6% predicted versus
      92.4% actual survival, in the validation cohort (C statistic, 0.63). Donor
      characteristics did not enhance model precision. CONCLUSIONS: Risk factors for 1
      year post-HTx graft loss differ on the basis of pre-HTx cardiac diagnosis.
      Modeling effectively stratifies the risk of graft loss in patients with
      cardiomyopathy and may be an adjunctive tool in allocation policies and center
      performance metrics.

PMID- 25587100
TI  - Systematic review of patients presenting with suspected myocardial infarction and
      nonobstructive coronary arteries.
AB  - BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA)
      is a puzzling clinical entity with no previous evaluation of the literature. This
      systematic review aims to (1) quantify the prevalence, risk factors, and 12-month
      prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological
      mechanisms underlying this disorder. METHODS AND RESULTS: Quantitative assessment
      of 28 publications using a meta-analytic approach evaluated the prevalence,
      clinical features, and prognosis of MINOCA. The prevalence of MINOCA was 6% [95%
      confidence interval, 5%-7%] with a median patient age of 55 years (95% confidence
      interval, 51-59 years) and 40% women. However, in comparison with those with
      myocardial infarction associated with obstructive coronary artery disease, the
      patients with MINOCA were more likely to be younger and female but less likely to
      have hyperlipidemia, although other cardiovascular risk factors were similar. All
      cause mortality at 12 months was lower in MINOCA (4.7%; 95% confidence interval,
      2.6%-6.9%) compared with myocardial infarction associated with obstructive
      coronary artery disease (6.7%, 95% confidence interval, 4.3%-9.0%). Qualitative
      assessment of 46 publications evaluating the underlying pathophysiology
      responsible for MINOCA revealed the presence of a typical myocardial infarct on
      cardiac magnetic resonance imaging in only 24% of patients, with myocarditis
      occurring in 33% and no significant abnormality in 26%. Coronary artery spasm was
      inducible in 27% of MINOCA patients, and thrombophilia disorders were detected in
      14%. CONCLUSIONS: MINOCA should be considered as a working diagnosis with
      multiple potential causes that require evaluation so that directed therapies may
      improve its guarded prognosis.

PMID- 25587101
TI  - Inhibition of PKR impairs angiogenesis through a VEGF pathway.
AB  - Peripheral artery disease (PAD) is a common clinical problem, and its
      pathophysiological mechanisms are incompletely understood. Double-stranded RNA
      activated protein kinase (PKR) is a ubiquitously expressed serine/threonine
      protein kinase. Although PKR has been reported in antivirus and the immune
      system, the role of PKR in vascular function, especially in angiogenesis, is
      still unclear. PKR(-/-) mice were used in our experiments. Blood flow recovery
      was significantly delayed in PKR(-/-) vs. WT mice (Laser Doppler detection, n =
      9, P < 0.01), accompanied by 34% reduced CD31-positive stain in ischemic muscle
      28 days after procedure (immunohistochemistry, n = 9, P < 0.05). PKR expression
      decreased in the first 12 h and increased to peak at 24 h in human umbilical vein
      endothelial cells (HUVECs) in response to hypoxia (Western blot analyses, n = 3,
      P < 0.05). Accordingly, phospho-PKR expression increased in HUVECs 24 h after
      treatment with hypoxia (Western blot analyses, n = 3, P < 0.05). Inhibition of
      PKR (siRNA transfection) reduced microtubule formation (Matrigel tube formation,
      n = 3, vs. control siRNA, P < 0.05) and migration (wound healing, n = 3, vs.
      control siRNA, P < 0.05) by 33 and 59%, respectively. Vascular endothelial growth
      factor (VEGF) expression in ischemic muscle from PKR(-/-) mice was significantly
      decreased by 54% 1 day after procedure (n = 3, P < 0.05, vs. WT) and by 63% 7
      days after procedure (n = 3, P < 0.01, vs. WT), respectively. At the same time,
      VEGF expression in HUVECs decreased by 21% (n = 3, P < 0.05, PKR siRNA vs.
      control siRNA). These findings demonstrate that PKR mediates angiogenesis through
      a VEGF pathway, which may form the basis for future intervention of PAD. 

PMID- 25587103
TI  - Alternative strategies needed to improve vascular access outcomes.

PMID- 25587104
TI  - Preventing aristolochic acid nephropathy.

PMID- 25587106
TI  - News feature: The search for what sets humans apart.

PMID- 25587105
TI  - Provider visit frequency and vascular access interventions in hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Medicare reimbursement policy encourages frequent
      provider visits to patients with ESRD undergoing hemodialysis. This study sought
      to determine whether more frequent face-to-face provider (physician and advanced
      practitioner) visits lead to more procedures and therapeutic interventions aimed
      at preserving arteriovenous fistulas and grafts, improved vascular access
      outcomes, and fewer related hospitalizations. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Multivariable regression was used to evaluate the association
      between provider (physician and advanced practitioner) visit frequency and
      interventions aimed at preserving vascular access, vascular access survival,
      hospitalization for vascular access infection, and outpatient antibiotic use in a
      cohort of 63,488 Medicare beneficiaries receiving hemodialysis in the United
      States. Medicare claims were used to identify the type of vascular access used,
      access-related events, and vascular access failure. RESULTS: One additional
      provider (physician and advanced practitioner) visit per month was associated
      with a 13% higher odds of receiving an intervention to preserve vascular access
      (95% confidence interval [95% CI], 12% to 14%) but was not associated with
      vascular access survival (hazard ratio, 1.01; 95% CI, 0.99 to 1.03). One
      additional provider visit was associated with a 9% (95% CI, 5% to 14%) lower odds
      of hospitalization for vascular access infection and a corresponding 9% (95% CI,
      5% to 14%) higher odds of outpatient intravenous antibiotic administration.
      However, the associated changes in absolute probabilities of hospitalization and
      antibiotic administration were small. CONCLUSIONS: More frequent face-to-face
      provider (physician and advanced practitioner) visits were associated with more
      procedures and therapeutic interventions aimed at preserving vascular accesses,
      but not with prolonged vascular access survival and only a small decrease in
      hospitalization for vascular access.

PMID- 25587102
TI  - Chronic dietary exposure to aristolochic acid and kidney function in native
      farmers from a Croatian endemic area and Bosnian immigrants.
AB  - BACKGROUND AND OBJECTIVES: Improvements in agricultural practices in Croatia have
      reduced exposure to consumption of aristolochic acid-contaminated flour and
      development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that
      Bosnian immigrants who settled in an endemic area in Croatia 15-30 years ago
      would be at lower risk of developing endemic nephropathy because of reduced
      exposure to aristolochic acid. To test this hypothesis, past and present exposure
      to aristolochic acid, proximal tubule damage as a hallmark of endemic
      nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional observational
      study from 2005 to 2010, 2161 farmers were divided into groups: indigenous
      inhabitants from endemic nephropathy and nonendemic nephropathy villages and
      Bosnian immigrants; alpha-1 microglobulin-to-creatinine ratio >31.5 mg/g and
      eGFR<60 ml/min per 1.73 m(2) were considered to be abnormal. RESULTS: CKD and
      proximal tubule damage prevalence was significantly lower in Bosnian immigrants
      than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001;
      1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants
      observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%)
      and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than
      homemade bread compared with Croatian farmers from endemic nephropathy villages
      (38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants
      observe significantly fewer Aristolochia plants growing in their fields compared
      with 15-30 years ago. Prior aristolochic acid exposure was associated with
      proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58;
      P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence
      interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent
      negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence
      interval, 0.19 to 0.86; P=0.02). CONCLUSIONS: Bosnian immigrants and
      autochthonous Croats residing in endemic areas are exposed significantly less to
      ingestion of aristolochic acid than in the past. The prevalence of endemic
      nephropathy and its associated urothelial cancers is predicted to decrease over
      time.

PMID- 25587109
TI  - An epidemiologic review of marijuana and cancer: an update.
AB  - Marijuana use is legal in two states and additional states are considering
      legalization. Approximately 18 million Americans are current marijuana users.
      There is currently no consensus on whether marijuana use is associated with
      cancer risk. Our objective is to review the epidemiologic studies on this
      possible association. We identified 34 epidemiologic studies on upper
      aerodigestive tract cancers (n = 11), lung cancer (n = 6), testicular cancer (n =
      3), childhood cancers (n = 6), all cancers (n = 1), anal cancer (n = 1), penile
      cancer (n = 1), non-Hodgkin lymphoma (n = 2), malignant primary gliomas (n = 1),
      bladder cancer (n = 1), and Kaposi sarcoma (n = 1). Studies on head and neck
      cancer reported increased and decreased risks, possibly because there is no
      association, or because risks differ by human papillomavirus status or geographic
      differences. The lung cancer studies largely appear not to support an association
      with marijuana use, possibly because of the smaller amounts of marijuana
      regularly smoked compared with tobacco. Three testicular cancer case-control
      studies reported increased risks with marijuana use [summary ORs, 1.56; 95%
      confidence interval (CI), 1.09-2.23 for higher frequency and 1.50 (95% CI, 1.08
      2.09) for >=10 years]. For other cancer sites, there is still insufficient data
      to make any conclusions. Considering that marijuana use may change due to
      legalization, well-designed studies on marijuana use and cancer are warranted.

PMID- 25587112
TI  - Correction: Androgen Receptor CAG Repeat Polymorphism and Risk of TMPRSS2:ERG
      Positive Prostate Cancer.

PMID- 25587110
TI  - Sun protection practices and sun exposure among children with a parental history
      of melanoma.
AB  - BACKGROUND: First-degree relatives of melanoma survivors have a substantially
      higher lifetime risk for melanoma than individuals with no family history.
      Exposure to ultraviolet radiation (UVR) is the primary modifiable risk factor for
      the disease. Reducing UV exposure through sun protection may be particularly
      important for children with a parental history of melanoma. Nonetheless, limited
      prior research has investigated sun protection practices and sun exposure among
      these children. METHODS: The California Cancer Registry was used to identify
      melanoma survivors eligible to participate in a survey to assess their children's
      sun protection practices and sun exposure. The survey was administered by mail,
      telephone, or web to Latino and non-Latino white melanoma survivors with at least
      one child (0-17 years; N = 324). RESULTS: Sun exposure was high and the rate of
      sunburn was equivalent to or higher than estimates from average-risk populations.
      Use of sun protection was suboptimal. Latino children were less likely to wear
      sunscreen and hats and more likely to wear sunglasses, although these differences
      disappeared in adjusted analyses. Increasing age of the child was associated with
      lower sun protection and higher risk for sunburn, whereas higher objective risk
      for melanoma predicted improved sun protection and a higher risk for sunburns.
      Perception of high barriers to sun protection was the strongest modifiable
      correlate of sun protection. CONCLUSIONS: Interventions to improve sun protection
      and reduce sun exposure and sunburns in high-risk children are needed. IMPACT:
      Intervening in high-risk populations may help reduce the burden of melanoma in
      the United States.

PMID- 25587113
TI  - Correction: weight change and survival after breast cancer in the after breast
      cancer pooling project.

PMID- 25587111
TI  - Metabolic syndrome and risk of endometrial cancer in the united states: a study
      in the SEER-medicare linked database.
AB  - BACKGROUND: Metabolic syndrome and its component feature, central obesity, are
      associated with endometrial cancer risk. It remains unclear whether associations
      with the other metabolic factors that comprise metabolic syndrome are independent
      of the obesity-endometrial cancer association. Furthermore, the link with
      specific endometrial cancer subtypes remains ill-defined, despite evidence of
      etiologic heterogeneity among these tumors. METHODS: In a case-control study
      within the SEER-Medicare linked database, we examined whether metabolic factors,
      individually or combined, were associated with endometrial cancer. Cases (n =
      16,323) were women diagnosed with endometrial cancer from 1993 through 2007.
      Controls (n = 100,751) were a 5% sample of female Medicare enrollees residing in
      the same SEER registry area as cases. Metabolic syndrome was defined using ICD-9
      CM codes from inpatient/outpatient diagnoses 1 to 3 years before case diagnosis
      and a comparable time period in controls. ORs and 95% confidence intervals (CI)
      were estimated using logistic regression. RESULTS: Endometrial cancer risk was
      associated with metabolic syndrome [OR (95% CI): 1.39 (1.32-1.47)] and its
      component factors: overweight/obesity [1.95 (1.80-2.11)], impaired fasting
      glucose [1.36 (1.30-1.43)], high blood pressure [1.31 (1.25-1.36)], and high
      triglycerides [1.13 (1.08-1.18)]. After adjusting for overweight/obesity, the
      increased risks associated with the metabolic syndrome factors remained.
      Heterogeneity of associations by subtype were not identified (Pheterogeneity =
      0.82). CONCLUSIONS: Among women age 65 and older in the United States, metabolic
      syndrome, and its component factors, increased endometrial cancer risk similarly
      across endometrial cancer subtypes. IMPACT: Strategies to reduce the prevalence
      of metabolic syndrome factors might have a favorable effect on endometrial cancer
      incidence.

PMID- 25587114
TI  - Laser speckle contrast imaging reveals large-scale synchronization of cortical
      autoregulation dynamics influenced by nitric oxide.
AB  - Synchronization of tubuloglomerular feedback (TGF) dynamics in nephrons that
      share a cortical radial artery is well known. It is less clear whether
      synchronization extends beyond a single cortical radial artery or whether it
      extends to the myogenic response (MR). We used LSCI to examine cortical perfusion
      dynamics in isoflurane-anesthetized, male Long-Evans rats. Inhibition of nitric
      oxide synthases by N(omega)-nitro-l-arginine methyl ester (l-NAME) was used to
      alter perfusion dynamics. Phase coherence (PC) was determined between all
      possible pixel pairs in either the MR or TGF band (0.09-0.3 and 0.015-0.06 Hz,
      respectively). The field of view (~4 * 5 mm) was segmented into synchronized
      clusters based on mutual PC. During the control period, the field of view was
      often contained within one cluster for both MR and TGF. PC was moderate for TGF
      and modest for MR, although significant in both. In both MR and TGF, PC exhibited
      little spatial variation. After l-NAME, the number of clusters increased in both
      MR and TGF. MR clusters became more strongly synchronized while TGF clusters
      showed small highly coupled, high-PC regions that were coupled with low PC to the
      remainder of the cluster. Graph theory analysis probed modularity of
      synchronization. It confirmed weak synchronization of MR during control that
      probably was not physiologically relevant. It confirmed extensive and long
      distance synchronization of TGF during control and showed increased modularity,
      albeit with larger modules seen in MR than in TGF after l-NAME. The results show
      widespread synchronization of MR and TGF that is differentially affected by
      nitric oxide. 

PMID- 25587115
TI  - Expression of a dominant negative PKA mutation in the kidney elicits a diabetes
      insipidus phenotype.
AB  - PKA plays a critical role in water excretion through regulation of the production
      and action of the antidiuretic hormone arginine vasopressin (AVP). The AVP
      prohormone is produced in the hypothalamus, where its transcription is regulated
      by cAMP. Once released into the circulation, AVP stimulates antidiuresis through
      activation of vasopressin 2 receptors in renal principal cells. Vasopressin 2
      receptor activation increases cAMP and activates PKA, which, in turn,
      phosphorylates aquaporin (AQP)2, triggering apical membrane accumulation,
      increased collecting duct permeability, and water reabsorption. We used single
      minded homolog 1 (Sim1)-Cre recombinase-mediated expression of a dominant
      negative PKA regulatory subunit (RIalphaB) to disrupt kinase activity in vivo and
      assess the role of PKA in fluid homeostasis. RIalphaB expression gave rise to
      marked polydipsia and polyuria; however, neither hypothalamic Avp mRNA expression
      nor urinary AVP levels were attenuated, indicating a primary physiological effect
      on the kidney. RIalphaB mice displayed a marked deficit in urinary concentrating
      ability and greatly reduced levels of AQP2 and phospho-AQP2. Dehydration induced
      Aqp2 mRNA in the kidney of both control and RIalphaB-expressing mice, but AQP2
      protein levels were still reduced in RIalphaB-expressing mutants, and mice were
      unable to fully concentrate their urine and conserve water. We conclude that
      partial PKA inhibition in the kidney leads to posttranslational effects that
      reduce AQP2 protein levels and interfere with apical membrane localization. These
      findings demonstrate a distinct physiological role for PKA signaling in both
      short- and long-term regulation of AQP2 and characterize a novel mouse model of
      diabetes insipidus. 

PMID- 25587117
TI  - Shear stress is normalized in glomerular capillaries following 5/6 nephrectomy.
AB  - Loss of significant functional renal mass results in compensatory structural and
      hemodynamic adaptations in the nephron. While these changes have been
      characterized in several injury models, how they affect hemodynamic forces at the
      glomerular capillary wall has not been adequately characterized, despite their
      potential physiological significance. Therefore, we used intravital multiphoton
      microscopy to measure the velocity of red blood cells in individual glomerular
      capillaries of normal rats and rats subjected to 5/6 nephrectomy. Glomerular
      capillary blood flow rate and wall shear stress were then estimated using
      previously established experimental and mathematical models to account for
      changes in hematocrit and blood rheology in small vessels. We found little change
      in the hemodynamic parameters in glomerular capillaries immediately following
      injury. At 2 wk postnephrectomy, significant changes in individual capillary
      blood flow velocity and volume flow rate were present. Despite these changes,
      estimated capillary wall shear stress was unchanged. This was a result of an
      increase in capillary diameter and changes in capillary blood rheology in
      nephrectomized rats. 

PMID- 25587116
TI  - Prolactin stimulates sodium and chloride ion channels in A6 renal epithelial
      cells.
AB  - Many hormonal pathways contribute to the regulation of renal epithelial sodium
      channel (ENaC) function, a key process for maintaining blood volume and
      controlling blood pressure. In the present study, we examined whether the peptide
      hormone prolactin (PRL) regulates ENaC function in renal epithelial cells (A6).
      Basolateral application of several different concentrations of PRL dramatically
      stimulated the transepithelial current in A6 cells, increasing both amiloride
      sensitive (ENaC) and amiloride-insensitive currents. Using cell-attached patch
      clamp, we determined that PRL increased both the number (N) and open probability
      (Po) of ENaC present in the apical membrane. Inhibition of PKA with H-89
      abolished the effect of PRL on amiloride-sensitive and insensitive
      transepithelial currents and eliminated the increase in ENaC NPo with PRL
      exposure. PRL also increased cAMP in A6 cells, consistent with signaling through
      the cAMP-dependent PKA pathway. We also identified that PRL induced activity of a
      2-pS anion channel with outward rectification, electrophysiological properties
      consistent with ClC4 or ClC5. RT-PCR only detected ClC4, but not ClC5
      transcripts. Here, we show for the first time that PRL activates sodium and
      chloride transport in renal epithelial cells via ENaC and ClC4. 

PMID- 25587118
TI  - Chloride channel ClC-5 binds to aspartyl aminopeptidase to regulate renal albumin
      endocytosis.
AB  - ClC-5 is a chloride/proton exchanger that plays an obligate role in albumin
      uptake by the renal proximal tubule. ClC-5 forms an endocytic complex with the
      albumin receptor megalin/cubilin. We have identified a novel ClC-5 binding
      partner, cytosolic aspartyl aminopeptidase (DNPEP; EC 3.4.11.21), that catalyzes
      the release of N-terminal aspartate/glutamate residues. The physiological role of
      DNPEP remains largely unresolved. Mass spectrometric analysis of proteins binding
      to the glutathione-S-transferase (GST)-ClC-5 C terminus identified DNPEP as an
      interacting partner. Coimmunoprecipitation confirmed that DNPEP and ClC-5 also
      associated in cells. Further experiments using purified GST-ClC-5 and His-DNPEP
      proteins demonstrated that the two proteins bound directly to each other. In
      opossum kidney (OK) cells, confocal immunofluorescence studies revealed that
      DNPEP colocalized with albumin-containing endocytic vesicles. Overexpression of
      wild-type DNPEP increased cell-surface levels of ClC-5 and albumin uptake.
      Analysis of DNPEP-immunoprecipitated products from rat kidney lysate identified
      beta-actin and tubulin, suggesting a role for DNPEP in cytoskeletal maintenance.
      A DNase I inhibition assay showed a significant decrease in the amount of G actin
      when DNPEP was overexpressed in OK cells, suggesting a role for DNPEP in
      stabilizing the cytoskeleton. DNPEP was not present in the urine of healthy rats;
      however, it was readily detected in the urine in rat models of mild and heavy
      proteinuria (diabetic nephropathy and anti-glomerular basement membrane disease,
      respectively). Urinary levels of DNPEP were found to correlate with the severity
      of proteinuria. Therefore, we have identified another key molecular component of
      the albumin endocytic machinery in the renal proximal tubule and describe a new
      role for DNPEP in stabilizing the actin cytoskeleton. 

PMID- 25587119
TI  - Urinary proteins induce lysosomal membrane permeabilization and lysosomal
      dysfunction in renal tubular epithelial cells.
AB  - Lysosomal membrane permeabilization (LMP) has been shown to cause the release of
      cathepsins and other hydrolases from the lysosomal lumen to the cytosol and
      initiate a cell death pathway. Whether proteinuria triggers LMP in renal tubular
      epithelial cells (TECs) to accelerate the progression of renal tubulointerstitial
      injury remains unclear. In the present study, we evaluated TEC injury as well as
      changes in lysosomal number, volume, activity, and membrane integrity after
      urinary protein overload in vivo and in vitro. Our results revealed that
      neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels
      were significantly increased in the urine of patients with minimal change
      nephrotic syndrome (MCNS) and the culture supernatant of HK-2 cells treated by
      urinary proteins extracted from MCNS patients. Urinary protein overload also
      induced apoptotic cell death in HK-2 cells. Importantly, we found that lysosomal
      volume and number were markedly increased in TECs of patients with MCNS and HK-2
      cells overloaded with urinary proteins. However, lysosome function, as assessed
      by proteolytic degradation of DQ-ovalbumin and cathepsin-B and cathepsin-L
      activities, was decreased in HK-2 cells overloaded with urinary proteins.
      Furthermore, urinary protein overload led to a diffuse cytoplasmic immunostaining
      pattern of cathepsin-B and irregular immunostaining of lysosome-associated
      membrane protein-1, accompanying a reduction in intracellular acidic components,
      which could be improved by pretreatment with antioxidant. Taken together, our
      results indicate that overloading of urinary proteins caused LMP and lysosomal
      dysfunction at least partly via oxidative stress in TECs. 

PMID- 25587120
TI  - Mitochondrial dysfunction in uremic cardiomyopathy.
AB  - Uremic cardiomyopathy (UCM) is characterized by metabolic remodelling,
      compromised energetics, and loss of insulin-mediated cardioprotection, which
      result in unsustainable adaptations and heart failure. However, the role of
      mitochondria and the susceptibility of mitochondrial permeability transition pore
      (mPTP) formation in ischemia-reperfusion injury (IRI) in UCM are unknown. Using a
      rat model of chronic uremia, we investigated the oxidative capacity of
      mitochondria in UCM and their sensitivity to ischemia-reperfusion mimetic oxidant
      and calcium stressors to assess the susceptibility to mPTP formation. Uremic
      animals exhibited a 45% reduction in creatinine clearance (P < 0.01), and cardiac
      mitochondria demonstrated uncoupling with increased state 4 respiration.
      Following IRI, uremic mitochondria exhibited a 58% increase in state 4
      respiration (P < 0.05), with an overall reduction in respiratory control ratio (P
      < 0.01). Cardiomyocytes from uremic animals displayed a 30% greater vulnerability
      to oxidant-induced cell death determined by FAD autofluorescence (P < 0.05) and
      reduced mitochondrial redox state on exposure to 200 MUM H2O2 (P < 0.01). The
      susceptibility to calcium-induced permeability transition showed that maximum
      rates of depolarization were enhanced in uremia by 79%. These results demonstrate
      that mitochondrial respiration in the uremic heart is chronically uncoupled.
      Cardiomyocytes in UCM are characterized by a more oxidized mitochondrial network,
      with greater susceptibility to oxidant-induced cell death and enhanced
      vulnerability to calcium-induced mPTP formation. Collectively, these findings
      indicate that mitochondrial function is compromised in UCM with increased
      vulnerability to calcium and oxidant-induced stressors, which may underpin the
      enhanced predisposition to IRI in the uremic heart. 

PMID- 25587121
TI  - Ovarian hormones and prolactin increase renal NaCl cotransporter phosphorylation.
AB  - Unique situations in female physiology require volume retention. Accordingly, a
      dimorphic regulation of the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC)
      has been reported, with a higher activity in females than in males. However,
      little is known about the hormones and mechanisms involved. Here, we present
      evidence that estrogens, progesterone, and prolactin stimulate NCC expression and
      phosphorylation. The sex difference in NCC abundance, however, is species
      dependent. In rats, NCC phosphorylation is higher in females than in males, while
      in mice both NCC expression and phosphorylation is higher in females, and this is
      associated with increased expression and phosphorylation of full-length STE-20
      proline-alanine-rich kinase (SPAK). Higher expression/phosphorylation of NCC was
      corroborated in humans by urinary exosome analysis. Ovariectomy in rats resulted
      in decreased expression and phosphorylation of the cotransporter and promoted the
      shift of SPAK isoforms toward the short inhibitory variant SPAK2. Conversely,
      estradiol or progesterone administration to ovariectomized rats restored NCC
      phosphorylation levels and shifted SPAK expression and phosphorylation towards
      the full-length isoform. Estradiol administration to male rats induced a
      significant increase in NCC phosphorylation. NCC is also modulated by prolactin.
      Administration of this peptide hormone to male rats induced increased
      phosphorylation of NCC, an effect that was observed even using the ex vivo kidney
      perfusion strategy. Our results indicate that estradiol, progesterone, and
      prolactin, the hormones that are involved in sexual cycle, pregnancy and
      lactation, upregulate the activity of NCC. 

PMID- 25587124
TI  - Transdermal contraception and the renin-angiotensin-aldosterone system in
      premenopausal women.
AB  - The oral contraceptive pill (OCP) activates the renin-angiotensin-aldosterone
      system (RAAS) through first-pass hepatic metabolism. Although usually benign,
      RAAS activation may have detrimental effects on renal and hemodynamic function in
      some women. Since combined hormonal contraception with the transdermal patch
      (EVRA) does not undergo first-pass hepatic metabolism, we hypothesized that the
      RAAS response would be different from that of OCP subjects. Thirty-five
      nonsmoking, premenopausal women (15 control subjects, 10 OCP subjects, and 10
      contraceptive patch subjects) without evidence of cardiovascular disease, renal
      disease, or diabetes were studied. Baseline angiotensinogen, renin, angiotensin
      II, aldosterone, and plasma renin activity were assessed along with hormonal and
      hemodynamic responses to simulated orthostatic stress using incremental lower
      body negative pressure (LBNP; -15, -25, and -40 mmHg). Baseline levels of
      angiotensinogen, angiotensin II, and plasma renin activity were significantly
      higher in OCP subjects compared with normotensive control and contraceptive patch
      subjects (P < 0.05), whereas aldosterone was significantly higher in OCP versus
      control subjects only (P < 0.05). Plasma renin levels were significantly lower at
      baseline in contraceptive patch subjects compared with normotensive control and
      OCP subjects (P < 0.05). In response to LBNP, increases in renin, angiotensin II,
      and aldosterone were attenuated in contraceptive patch subjects in conjunction
      with an exaggerated decline in mean arterial pressure (P < 0.05 vs. control and
      OCP subjects). The contraceptive patch in healthy premenopausal women is
      associated with an impaired ability to maintain blood pressure in response to
      LBNP, possibly due to insensitivity of the endogenous RAAS. Further evaluation
      may be beneficial in women with kidney disease. 

PMID- 25587122
TI  - Flow regulation of endothelin-1 production in the inner medullary collecting
      duct.
AB  - Collecting duct-derived endothelin (ET)-1 is an autocrine inhibitor of Na(+) and
      water reabsorption; its deficiency causes hypertension and water retention.
      Extracellular fluid volume expansion increases collecting duct ET-1, thereby
      promoting natriuresis and diuresis; however, how this coupling between volume
      expansion and collecting duct ET-1 occurs is incompletely understood. One
      possibility is that volume expansion increases tubular fluid flow. To investigate
      this, cultured IMCD3 cells were subjected to static or flow conditions. Exposure
      to a shear stress of 2 dyn/cm(2) for 2 h increased ET-1 mRNA content by ~2.3
      fold. Absence of perfusate Ca(2+), chelation of intracellular Ca(2+), or
      inhibition of Ca(2+) signaling (calmodulin, Ca(2+)/calmodulin-dependent kinase,
      calcineurin, PKC, or phospholipase C) prevented the flow response. Evaluation of
      possible flow-activated Ca(2+) entry pathways revealed no role for transient
      receptor potential (TRP)C3, TRPC6, and TRPV4; however, cells with TRPP2
      (polycystin-2) knockdown had no ET-1 flow response. Flow increased intracellular
      Ca(2+) was blunted in TRPP2 knockdown cells. Nonspecific blockade of P2
      receptors, as well as specific inhibition of P2X7 and P2Y2 receptors, prevented
      the ET-1 flow response. The ET-1 flow response was not affected by inhibition of
      either epithelial Na(+) channels or the mitochondrial Na(+)/Ca(2+) exchanger.
      Taken together, these findings provide evidence that in IMCD3 cells, flow, via
      polycystin-2 and P2 receptors, engages Ca(2+)-dependent signaling pathways that
      stimulate ET-1 synthesis. 

PMID- 25587126
TI  - His and hers hypertension-down to a T?

PMID- 25587123
TI  - Ret is critical for podocyte survival following glomerular injury in vivo.
AB  - Podocyte injury and loss directly cause proteinuria and the progression to
      glomerulosclerosis. Elucidation of the mechanisms of podocyte survival and
      recovery from injury is critical for designing strategies to prevent the
      progression of glomerular diseases. Glial cell line-derived neurotrophic factor
      (GDNF) and its receptor tyrosine kinase, Ret, are upregulated in both nonimmune
      and immune-mediated in vitro and in vivo models of glomerular diseases. We
      investigated whether Ret, a known receptor tyrosine kinase critical for kidney
      morphogenesis and neuronal growth and development, is necessary for glomerular
      and podocyte development and survival in vivo. Since deletions of both GDNF and
      Ret result in embryonic lethality due to kidney agenesis, we examined the role of
      Ret in vivo by generating mice with a conditional deletion of Ret in podocytes
      (Ret(flox/flox); Nphs2-Cre). In contrast to the lack of any developmental and
      maintenance deficits, Ret(flox/flox); Nphs2-Cre mice showed a significantly
      enhanced susceptibility to adriamycin nephropathy, a rodent model of focal
      segmental glomerulosclerosis. Thus, these findings demonstrated that the Ret
      signaling pathway is important for podocyte survival and recovery from glomerular
      injury in vivo. 

PMID- 25587125
TI  - Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1
      accelerates podocyte loss via uPAR-mediated beta1-integrin endocytosis.
AB  - Podocyte-endothelial cell cross-talk is paramount for maintaining the filtration
      barrier. The present study investigated the endothelial response to podocyte
      injury and its subsequent role in glomerulosclerosis using the podocyte-specific
      injury model of NEP25/LMB2 mice. NEP25/LMB2 mice showed proteinuria and local
      podocyte loss accompanied by thrombotic microangiopathy on day 8. Mice showed an
      increase of glomerular plasminogen activator inhibitor type 1 (PAI-1) mRNA and
      aberrant endothelial PAI-1 protein already on day 1, before thrombosis and
      proteinuria. A PAI-1-specific inhibitor reduced proteinuria and thrombosis and
      preserved podocyte numbers in NEP25/LMB2 mice by stabilization of beta1-integrin
      translocation. Heparin loading significantly reduced thrombotic formation,
      whereas proteinuria and podocyte numbers were unchanged. Immortalized podocytes
      treated with PAI-1 and the urokinase plasminogen activator (uPA) complex caused
      significant cell detachment, whereas podocytes treated with PAI-1 or uPA alone or
      with the PAI-1/uPA complex pretreated with an anti-uPA receptor (uPAR) antibody
      failed to cause detachment. Confocal microscopy and cell surface biotinylation
      experiments showed that internalized beta1-integrin was found together with uPAR
      in endocytotic vesicles. The administration of PAI-1 inhibitor or uPAR-blocking
      antibody protected cultured podocytes from cell detachment. In conclusion, PAI
      1/uPA complex-mediated uPAR-dependent podocyte beta1-integrin endocytosis
      represents a novel mechanism of glomerular injury leading to progressive
      podocytopenia. This aberrant cross-talk between podocytes and endothelial cells
      represents a feedforward injury response driving podocyte loss and progressive
      glomerulosclerosis. 

PMID- 25587127
TI  - Mechanism-based inhibitory and peroxisome proliferator-activated receptor alpha
      dependent modulating effects of silybin on principal hepatic drug-metabolizing
      enzymes.
AB  - Silybin, a major pharmacologically active compound in silymarin, has been widely
      used in combination with other prescriptions in the clinic to treat hepatitis and
      a host of other diseases. Previous studies suggested that silybin is a potential
      inhibitor of multiple drug-metabolizing enzymes (DMEs); however, the in vitro to
      in vivo translation and the mechanisms involved remain established. The aim of
      this study was to provide a mechanistic understanding of the regulatory effects
      of silybin on principal DMEs. Silybin (50 or 150 mg/kg/d) was administered to
      mice for a consecutive 14 days. The plasma and hepatic exposure of silybin were
      detected; the mRNA, protein levels, and enzyme activities of principal DMEs were
      determined. The results demonstrated that the enzyme activities of CYP1A2, CYP2C,
      CYP3A11, and UGT1A1 were significantly repressed, whereas little alteration of
      the mRNA and protein levels was observed. Silybin inhibits these DMEs in a
      mechanism-based and/or substrate-competitive manner. More importantly, silybin
      was found to be a weak agonist of peroxisome proliferator-activated receptor
      (PPAR)alpha, as evidenced from the molecular docking, reporter gene assay, and
      the targeting gene expression analysis. However, silybin could significantly
      compromise the activation of PPARalpha by fenofibrate, characterized with
      significantly repressed expression of PPARalpha targeting genes, including L
      FABP, ACOX1, and UGT1A6. This study suggests that silybin, despite its low
      bioavailability, may inhibit enzyme activities of multiple DMEs in a mechanism
      based mode, and more importantly, may confer significant drug-drug interaction
      with PPARalpha agonists via the repression of PPARalpha activation in a
      competitive mode. 

PMID- 25587128
TI  - Breast cancer resistance protein (ABCG2) in clinical pharmacokinetics and drug
      interactions: practical recommendations for clinical victim and perpetrator drug
      drug interaction study design.
AB  - Breast cancer resistance protein (BCRP; ABCG2) limits intestinal absorption of
      low-permeability substrate drugs and mediates biliary excretion of drugs and
      metabolites. Based on clinical evidence of BCRP-mediated drug-drug interactions
      (DDIs) and the c.421C>A functional polymorphism affecting drug efficacy and
      safety, both the US Food and Drug Administration and European Medicines Agency
      recommend preclinical evaluation and, when appropriate, clinical assessment of
      BCRP-mediated DDIs. Although many BCRP substrates and inhibitors have been
      identified in vitro, clinical translation has been confounded by overlap with
      other transporters and metabolic enzymes. Regulatory recommendations for BCRP
      mediated clinical DDI studies are challenging, as consensus is lacking on the
      choice of the most robust and specific human BCRP substrates and inhibitors and
      optimal study design. This review proposes a path forward based on a
      comprehensive analysis of available data. Oral sulfasalazine (1000 mg, immediate
      release tablet) is the best available clinical substrate for intestinal BCRP,
      oral rosuvastatin (20 mg) for both intestinal and hepatic BCRP, and intravenous
      rosuvastatin (4 mg) for hepatic BCRP. Oral curcumin (2000 mg) and lapatinib (250
      mg) are the best available clinical BCRP inhibitors. To interrogate the worst
      case clinical BCRP DDI scenario, study subjects harboring the BCRP c.421C/C
      reference genotype are recommended. In addition, if sulfasalazine is selected as
      the substrate, subjects having the rapid acetylator phenotype are recommended. In
      the case of rosuvastatin, subjects with the organic anion-transporting
      polypeptide 1B1 c.521T/T genotype are recommended, together with monitoring of
      rosuvastatin's cholesterol-lowering effect at baseline and DDI phase. A proof-of
      concept clinical study is being planned by a collaborative consortium to evaluate
      the proposed BCRP DDI study design. 

PMID- 25587129
TI  - Associations of HSD11B1 polymorphisms with tacrolimus concentrations in Chinese
      renal transplant recipients with prednisone combined therapy.
AB  - Tacrolimus requires close therapeutic drug monitoring because of its narrow
      therapeutic index and marked interindividual pharmacokinetic variation. In this
      study, we investigated the associations of polymorphisms in the gene encoding
      11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) with tacrolimus
      concentrations in Chinese renal transplant recipients during the early
      posttransplantation stage. A total of 258 renal transplant recipients receiving
      tacrolimus with prednisone (30 mg) combined therapy were genotyped for HSD11B1
      rs846908, rs846910, rs4844880, and CYP3A5*3 polymorphisms. Tacrolimus trough
      concentrations were determined on days 6-9 after transplantation, measured by a
      chemiluminescent microparticle immunoassay. Among the CYP3A5 expressers, the dose
      adjusted trough concentration (C0/D) of tacrolimus in HSD11B1 rs846908 AA
      homozygous individuals was considerably lower than found in GG+GA carriers [56.2
      (23.9-86.6) versus 76.7 (12.6-220.0) (ng/ml)/(mg/kg), P = 0.0204]; HSD11B1
      rs846910 AA homozygotes had a lower tacrolimus C0/D compared with GG+GA carriers
      [51.2 (23.9-86.6) versus 76.3 (12.6-220.0) (ng/ml)/(mg/kg), P = 0.0367]; carriers
      with the HSD11B1 rs4844880 AA genotype had a significantly lower tacrolimus C0/D
      with respect to carriers of TT+TA genotypes [61.3 (23.9-97.5) versus 77.2 (12.6
      220.0) (ng/ml)/(mg/kg), P = 0.0002]; the HSD11B1 AA-AA-AA haplotype carriers had
      a lower tacrolimus C0/D than noncarriers [51.2 (23.9-86.6) versus 76.3 (12.6
      220.0) (ng/ml)/(mg/kg), P = 0.0367]. These findings illustrate that the HSD11B1
      genotypes are closely correlated with tacrolimus trough concentrations,
      suggesting that these polymorphisms may be useful for safer dosing of tacrolimus.

PMID- 25587130
TI  - Home blood pressure monitoring with patient-initiated drug titration reduces
      blood pressure in high-risk patients with hypertension.

PMID- 25587131
TI  - 64Cu antibody-targeting of the T-cell receptor and subsequent internalization
      enables in vivo tracking of lymphocytes by PET.
AB  - T cells are key players in inflammation, autoimmune diseases, and immunotherapy.
      Thus, holistic and noninvasive in vivo characterizations of the temporal
      distribution and homing dynamics of lymphocytes in mammals are of special
      interest. Herein, we show that PET-based T-cell labeling facilitates
      quantitative, highly sensitive, and holistic monitoring of T-cell homing patterns
      in vivo. We developed a new T-cell receptor (TCR)-specific labeling approach for
      the intracellular labeling of mouse T cells. We found that continuous TCR plasma
      membrane turnover and the endocytosis of the specific (64)Cu-monoclonal antibody
      (mAb)-TCR complex enables a stable labeling of T cells. The TCR-mAb complex was
      internalized within 24 h, whereas antigen recognition was not impaired. Harmful
      effects of the label on the viability, DNA-damage and apoptosis-necrosis
      induction, could be minimized while yielding a high contrast in in vivo PET
      images. We were able to follow and quantify the specific homing of systemically
      applied (64)Cu-labeled chicken ovalbumin (cOVA)-TCR transgenic T cells into the
      pulmonary and perithymic lymph nodes (LNs) of mice with cOVA-induced airway
      delayed-type hypersensitivity reaction (DTHR) but not into pulmonary and
      perithymic LNs of naive control mice or mice diseased from turkey or pheasant OVA
      induced DTHR. Our protocol provides consequent advancements in the detection of
      small accumulations of immune cells in single LNs and specific homing to the
      sites of inflammation by PET using the internalization of TCR-specific mAbs as a
      specific label of T cells. Thus, our labeling approach is applicable to other
      cells with constant membrane receptor turnover. 

PMID- 25587133
TI  - Representing "stuff" in visual cortex.

PMID- 25587132
TI  - Genomic and proteomic characterization of "Candidatus Nitrosopelagicus brevis":
      an ammonia-oxidizing archaeon from the open ocean.
AB  - Thaumarchaeota are among the most abundant microbial cells in the ocean, but
      difficulty in cultivating marine Thaumarchaeota has hindered investigation into
      the physiological and evolutionary basis of their success. We report here a
      closed genome assembled from a highly enriched culture of the ammonia-oxidizing
      pelagic thaumarchaeon CN25, originating from the open ocean. The CN25 genome
      exhibits strong evidence of genome streamlining, including a 1.23-Mbp genome, a
      high coding density, and a low number of paralogous genes. Proteomic analysis
      recovered nearly 70% of the predicted proteins encoded by the genome,
      demonstrating that a high fraction of the genome is translated. In contrast to
      other minimal marine microbes that acquire, rather than synthesize, cofactors,
      CN25 encodes and expresses near-complete biosynthetic pathways for multiple
      vitamins. Metagenomic fragment recruitment indicated the presence of DNA
      sequences >90% identical to the CN25 genome throughout the oligotrophic ocean. We
      propose the provisional name "Candidatus Nitrosopelagicus brevis" str. CN25 for
      this minimalist marine thaumarchaeon and suggest it as a potential model system
      for understanding archaeal adaptation to the open ocean. 

PMID- 25587135
TI  - Altruism, self-interest, and energy consumption.

PMID- 25587134
TI  - The NMR-Rosetta capsid model of M13 bacteriophage reveals a quadrupled
      hydrophobic packing epitope.
AB  - Filamentous phage are elongated semiflexible ssDNA viruses that infect bacteria.
      The M13 phage, belonging to the family inoviridae, has a length of ~1 MUm and a
      diameter of ~7 nm. Here we present a structural model for the capsid of intact
      M13 bacteriophage using Rosetta model building guided by structure restraints
      obtained from magic-angle spinning solid-state NMR experimental data. The C5
      subunit symmetry observed in fiber diffraction studies was enforced during model
      building. The structure consists of stacked pentamers with largely alpha helical
      subunits containing an N-terminal type II beta-turn; there is a rise of 16.6-16.7
      A and a tilt of 36.1-36.6 degrees  between consecutive pentamers. The packing of
      the subunits is stabilized by a repeating hydrophobic stacking pocket; each
      subunit participates in four pockets by contributing different hydrophobic
      residues, which are spread along the subunit sequence. Our study provides, to our
      knowledge, the first magic-angle spinning NMR structure of an intact filamentous
      virus capsid and further demonstrates the strength of this technique as a method
      of choice to study noncrystalline, high-molecular-weight molecular assemblies. 

PMID- 25587136
TI  - The value of monitoring to control evolving populations.
AB  - Populations can evolve to adapt to external changes. The capacity to evolve and
      adapt makes successful treatment of infectious diseases and cancer difficult.
      Indeed, therapy resistance has become a key challenge for global health.
      Therefore, ideas of how to control evolving populations to overcome this threat
      are valuable. Here we use the mathematical concepts of stochastic optimal control
      to study what is needed to control evolving populations. Following established
      routes to calculate control strategies, we first study how a polymorphism can be
      maintained in a finite population by adaptively tuning selection. We then
      introduce a minimal model of drug resistance in a stochastically evolving cancer
      cell population and compute adaptive therapies. When decisions are in this manner
      based on monitoring the response of the tumor, this can outperform established
      therapy paradigms. For both case studies, we demonstrate the importance of high
      resolution monitoring of the target population to achieve a given control
      objective, thus quantifying the intuition that to control, one must monitor. 

PMID- 25587137
TI  - Reply to Scahill: Behavioral outcome measures in autism.

PMID- 25587138
TI  - Uncommon use of common measures in sulforaphane trial.

PMID- 25587139
TI  - Reply to Evans and Bar-Oz et al.: Recovering ecological pattern and process in
      Ancient Egypt.

PMID- 25587140
TI  - Ancient Egypt's fluctuating fauna: ecological events or cultural constructs?

PMID- 25587141
TI  - Mammalian extinction in ancient Egypt, similarities with the southern Levant.

PMID- 25587143
TI  - On measuring the bending strength of septate grass stems.
AB  - * PREMISE OF THE STUDY: Reliable testing methodologies are a fundamental tenet of
      scientific research. However, very little information is found in the literature
      explaining how to accurately measure the structural bending strength of plant
      stems. It was hypothesized that the most commonly employed loading configuration
      used in bending experiments (placement of loading anvil at an internodal region
      of the stem or stalk) may significantly alter test results and introduce errors
      in bending strength measurements of plant stems.* METHODS: Four types of
      mechanical tests were performed on bamboo (Phyllostachys aurea), giant reed
      (Arundo donax), and maize (Zea mays) to investigate how different loading
      configurations employed during three-point bending experiments affect test
      results of septate grass stems and to develop a testing protocol that provides
      reliable measures of stalk bending strength.* RESULTS: RESULTS confirmed the
      hypothesis that internodal-loaded three-point bending test can produce erroneous
      bending strength measurements. This testing methodology causes plant stems to
      break prematurely and produces failure types and patterns incongruent with stalks
      that broke in their natural (in situ) environment. In contrast, a modified test
      configuration produces natural failure patterns and more accurate measurements of
      bending strength.* CONCLUSION: Reliable measurements of stalk bending strength
      can be obtained by maximizing the span length of bending tests and placing the
      loading anvil at stronger and denser nodal tissues. These results are relevant to
      ecological and evolutionary plant biomechanics studies as well as agronomic
      breeding studies focused on measuring plant phenotypes such as stalk lodging
      strength, or on improving bending strength of septate plant stems.

PMID- 25587144
TI  - Multiscale stress-strain characterization of onion outer epidermal tissue in wet
      and dry states.
AB  - * PREMISE OF THE STUDY: Quantitative measurements of water's effects on the
      tension response of plant tissue will assist in understanding the regulatory
      mechanism underlying expansive growth. Such measurements should be multiscale in
      nature to account for plants' hierarchical structure.* METHODS: Outer onion
      epidermal tissues were cut and bonded to uniaxial displacement-controlled
      mechanical loading devices to apply and measure the force on the sample.
      Fluorescent polystyrene beads (500 nm in diameter) were dispersed on the sample
      surface under various levels of tensile load conditions to obtain displacement
      maps with a confocal fluorescent microscope. The resulting strain was measured
      using a digital image correlation technique by tracking individual bead
      displacements. The applied forces were obtained by measuring the displacement of
      the calibrated force-sensing device. Tissue- and cell-scale mechanical properties
      were quantified by calculating the applied stress and the corresponding global
      and local strains.* KEY RESULTS: The Young's modulus values of individual cell
      walls of dehydrated and rehydrated samples were 3.0 +/- 1.0 GPa and 0.4 +/- 0.2
      GPa, respectively, and are different from the Young's modulus values of the
      global tissue-scale dehydrated and rehydrated samples, which were 1.9 +/- 0.3 GPa
      and 0.08 +/- 0.02 GPa, respectively. Poisson's ratio increased more than 3-fold
      due to hydration.* CONCLUSION: The results on global, cell-to-cell, and point-to
      point mechanical property variations suggest the importance of the mechanical
      contribution of extracellular features including the middle lamella, cell shape,
      and dimension. This study shows that a multiscale investigation is essential for
      fundamental insights into the hierarchical deformation of biological systems.

PMID- 25587145
TI  - Transcriptional response of Arabidopsis seedlings during spaceflight reveals
      peroxidase and cell wall remodeling genes associated with root hair development.
AB  - * PREMISE OF THE STUDY: Plants will be an important component of advanced life
      support systems during space exploration missions. Therefore, understanding their
      biology in the spacecraft environment will be essential before they can be used
      for such systems.* METHODS: Seedlings of Arabidopsis thaliana were grown for 2 wk
      in the Biological Research in Canisters (BRIC) hardware on board the second to
      the last mission of the space shuttle Discovery (STS-131). Transcript profiles
      between ground controls and space-grown seedlings were compared using stringent
      selection criteria.* KEY RESULTS: Expression of transcripts associated with
      oxidative stress and cell wall remodeling was repressed in microgravity. These
      downregulated genes were previously shown to be enriched in root hairs consistent
      with seedling phenotypes observed in space. Mutations in genes that were
      downregulated in microgravity, including two uncharacterized root hair-expressed
      class III peroxidase genes (PRX44 and PRX57), led to defective polar root hair
      growth on Earth. PRX44 and PRX57 mutants had ruptured root hairs, which is a
      typical phenotype of tip-growing cells with defective cell walls and those
      subjected to stress.* CONCLUSIONS: Long-term exposure to microgravity negatively
      impacts tip growth by repressing expression of genes essential for normal root
      hair development. Whereas changes in peroxidase gene expression leading to
      reduced root hair growth in space are actin-independent, root hair development
      modulated by phosphoinositides could be dependent on the actin cytoskeleton.
      These results have profound implications for plant adaptation to microgravity
      given the importance of tip growing cells such as root hairs for efficient
      nutrient capture.

PMID- 25587147
TI  - An invasive plant alters pollinator-mediated phenotypic selection on a native
      congener.
AB  - * PREMISE OF STUDY: Recent studies suggest that invasive plants compete
      reproductively with native plants by reducing the quantity or quality of
      pollinator visits. Although these studies have revealed ecological consequences
      of pollinator-mediated competition between invasive and native plants, the
      evolutionary outcomes of these interactions remain largely unexplored.* METHODS:
      We studied the ecological and evolutionary impact of pollinator-mediated
      competition with an invasive jewelweed, Impatiens glandulifera, on a co-occurring
      native congener, I. capensis. Using a pollinator choice experiment, a hand
      pollination experiment, and a selection analysis, we addressed the following
      questions: (1) Do native pollinators show preference for the invasive or native
      jewelweed, and do they move between the two species? (2) Does invasive jewelweed
      pollen inhibit seed production in the native plant? (3) Does the invasive
      jewelweed alter phenotypic selection on the native plant's floral traits?* KEY
      RESULTS: The pollinator choice experiment showed that pollinators strongly
      preferred the invasive jewelweed. The hand pollination experiment demonstrated
      that invasive pollen inhibited seed production in the native plant. The selection
      analysis showed that the presence of the invasive jewelweed altered phenotypic
      selection on corolla height in the native plant.* CONCLUSIONS: Invasive plants
      have the potential to alter phenotypic selection on floral traits in native plant
      populations. If native plants can evolve in response to this altered selection
      pressure, the evolution of floral traits may play an important role in permitting
      long-term coexistence of native and invasive plants.

PMID- 25587146
TI  - Ecological niche differentiation of polyploidization is not supported by
      environmental differences among species in a cosmopolitan grass genus.
AB  - * PREMISE OF THE STUDY: Polyploidization frequently results in the creation of
      new plant species, the establishment of which is thought to often be facilitated
      by ecological niche differentiation from the diploid species. We tested this
      hypothesis using the cosmopolitan grass genus Phalaris (Poaceae), consisting of
      19 species that range from diploid to tetraploid to hexaploid. Specifically, we
      tested whether (1) polyploids occupy more extreme environments and/or (2) have
      broader niche breadths and/or (3) whether the polyploid species' distributions
      indicate a niche shift from diploid species.* METHODS: We employed a
      bootstrapping approach using distribution data for each species and eight
      environmental variables to investigate differences between species in the means,
      extremes, and breadths of each environmental variable. We used a kernel smoothing
      technique to quantify niche overlap between species.* KEY RESULTS: Although we
      found some support for the three hypotheses for a few diploid-polyploid pairs and
      for specific environmental variables, none of these hypotheses were generally
      supported.* CONCLUSIONS: Our results suggest that these commonly held hypotheses
      about the effects of polyploidization on ecological distributions are not
      universally applicable. Correlative biogeographic studies like ours provide a
      necessary first step for suggesting specific hypotheses that require experimental
      verification. A combination of genetic, physiological, and ecological studies
      will be required to achieve a better understanding of the role of
      polyploidization in niche evolution.

PMID- 25587148
TI  - Dynamic extrafloral nectar production: the timing of leaf damage affects the
      defensive response in Senna mexicana var. chapmanii (Fabaceae).
AB  - * PREMISE OF THE STUDY: Extrafloral nectar (EFN) mediates food for protection
      mutualisms between plants and defensive insects. Understanding sources of
      variation in EFN production is important because such variations may affect the
      number and identity of visitors and the effectiveness of plant defense. We
      investigated the influence of plant developmental stage, time of day, leaf age,
      and leaf damage on EFN production in Senna mexicana var. chapmanii. The observed
      patterns of variation in EFN production were compared with those predicted by
      optimal defense theory.* METHODS: Greenhouse experiments with potted plants were
      conducted to determine how plant age, time of day, and leaf damage affected EFN
      production. A subsequent field study was conducted to determine how leaf damage,
      and the resulting increase in EFN production, affected ant visitation in S.
      chapmanii.* KEY RESULTS: More nectar was produced at night and by older plants.
      Leaf damage resulted in increased EFN production, and the magnitude of the
      response was greater in plants damaged in the morning than those damaged at
      night. Damage to young leaves elicited a stronger defensive response than damage
      to older leaves, in line with optimal defense theory. Damage to the leaves of S.
      chapmanii also resulted in significantly higher ant visitation in the field.*
      CONCLUSIONS: Extrafloral nectar is an inducible defense in S. chapmanii.
      Developmental variations in its production support the growth differentiation
      balance hypothesis, while within-plant variations and damage responses support
      optimal defense theory.

PMID- 25587149
TI  - Pollen limitation and the contribution of autonomous selfing to fruit and seed
      set in a rewarding orchid.
AB  - * PREMISE OF THE STUDY: Although rewarding orchids are believed to have a high
      pollination efficiency, pollination success is often low, suggesting that
      rewarding orchids may be prone to pollen limitation. Assuming that selfing
      contributes significantly to fruit and seed set (i.e., reproductive assurance)
      and that the quality of selfed seeds is high (i.e., low inbreeding depression),
      it can be hypothesized that under these circumstances populations evolve to
      facultative or even complete self-pollination.* METHODS: In this study, we
      performed emasculation and pollen supplementation experiments in the field to
      assess the extent of outcross pollen limitation and the contribution of
      autonomous self-pollination to fruit and seed set in the rewarding orchid
      Epipactis palustris. Hand-pollinations using cross and self-pollen were performed
      in the greenhouse to investigate the impact of selfing on seed set and seed
      quality and to assess the magnitude of inbreeding depression.* KEY RESULTS: Fruit
      set under natural conditions was high: ca. 70% of all flowers set fruit.
      Percentage fruit set of emasculated plants was 56%, implying that fruit set in
      about 14% of all flowers was the result of autonomous self-pollination. Pollen
      supplementation significantly increased fruit and seed set, indicating strong
      outcross pollen limitation. Hand-pollination with cross pollen resulted in
      significantly higher seed set and seed quality compared with manual self
      pollination, indicating high levels of early inbreeding depression (delta = 0.46
      +/- 0.08).* CONCLUSIONS: Overall, these results indicate that, despite the high
      pollination efficiency, populations of this rewarding orchid species were
      strongly pollen limited. Costs of early inbreeding depression, on the other hand,
      were high, which may prevent rapid evolution of complete selfing.

PMID- 25587151
TI  - Direct and indirect effects of environmental variability on growth and
      survivorship of pre-reproductive Joshua trees, Yucca brevifolia Engelm.
      (Agavaceae).
AB  - * PREMISE OF STUDY: Accurate demographic information about long-lived plant
      species is important for understanding responses to large-scale disturbances,
      including climate change. It is challenging to obtain these data from desert
      perennial plants because seedling establishment is exceptionally rare, and
      estimates of survival are lacking for their vulnerable early stages. Desert
      wildfires, urbanization, and climate change influence the persistence of the long
      lived Yucca brevifolia. Quantitative demographic attributes are crucial for
      understanding how populations will respond to disturbances and where populations
      will recede or advance under future climate scenarios.* METHODS: We measured
      survival in a cohort of 53 pre-reproductive Y. brevifolia at Yucca Flat, Nevada,
      USA, for 22 yr and recorded their growth, nurse-plant relationships, and
      herbivory.* KEY RESULTS: Herbivory by black-tailed jackrabbits (Lepus
      californicus) caused severe losses of plants during the first and second years
      (45% and 31%, respectively). Surviving plants experienced <2.5% annual mortality.
      Survival for the population was 19% over 22 yr. Plants <25 cm in height had lower
      life expectancy. Average growth rate (+/- SD) for plants that survived to the
      last census was 3.12 +/- 1.96 cm yr(-1), and growth rates were positively
      associated with precipitation. Thirty-year-old Y. brevifolia had not yet
      reproduced.* CONCLUSIONS: A rare establishment event for Y. brevifolia during
      1983-1984, triggered by above-average summer rainfall, provided a unique
      opportunity to track early survival and growth. Infrequent but acute episodes of
      herbivory during drought influenced demography for decades. Variability in
      survival among young Y. brevifolia indicates that size-dependent demographic
      variables will improve forecasts for this long-lived desert species under
      predicted regional climate change.

PMID- 25587150
TI  - Plastic responses of native plant root systems to the presence of an invasive
      annual grass.
AB  - * PREMISE OF THE STUDY: The ability to respond to environmental change via
      phenotypic plasticity may be important for plants experiencing disturbances such
      as climate change and plant invasion. Responding to belowground competition
      through root plasticity may allow native plants to persist in highly invaded
      systems such as the cold deserts of the Intermountain West, USA.* METHODS: We
      investigated whether Poa secunda, a native bunchgrass, could alter root
      morphology in response to nutrient availability and the presence of a competitive
      annual grass. Seeds from 20 families were grown with high and low nutrients and
      harvested after 50 d, and seeds from 48 families, grown with and without Bromus
      tectorum, were harvested after ~2 or 6 mo. We measured total biomass, root mass
      fraction, specific root length (SRL), root tips, allocation to roots of varying
      diameter, and plasticity in allocation.* KEY RESULTS: Plants had many parallel
      responses to low nutrients and competition, including increased root tip
      production, a trait associated with tolerance to reduced resources, though
      families differed in almost every trait and correlations among trait changes
      varied among experiments, indicating flexibility in plant responses. Seedlings
      actively increased SRL and fine root allocation under competition, while older
      seedlings also increased coarse root allocation, a trait associated with
      increased tolerance, and increased root mass fraction.* CONCLUSIONS: The high
      degree of genetic variation for root plasticity within natural populations could
      aid in the long-term persistence of P. secunda because phenotypic plasticity may
      allow native species to persist in invaded and fluctuating resource environments.

PMID- 25587152
TI  - Environmental correlates of cytotype distribution in Andropogon gerardii
      (Poaceae).
AB  - * PREMISE OF THE STUDY: Information about geographic distribution of cytotypes
      can provide insight into the origin and maintenance of autopolyploid complexes
      and builds a foundation for understanding cytotype differentiation and the
      dynamics of mixed-ploidy populations. Here, we investigate environmental
      correlates of the geographic distributions of 6x and 9x individuals in the
      ecologically dominant grass Andropogon gerardii to examine the role of climate in
      shaping patterns of cytotype distribution in this species.* METHODS: Flow
      cytometry was used to estimate ploidy level in 352 individuals from 32
      populations across North America. Ecological differentiation of cytotypes was
      tested by relating BIOCLIM variables to cytotype distribution using principal
      components analysis and partial linear regression.* KEY RESULTS: Broad geographic
      sampling confirmed two primary cytotypes-6x (hexaploid) and 9x (enneaploid)-and
      revealed that 9x plants are more common than previously thought. Enneaploids
      occur frequently in the southern portions of the range, with hexaploids
      dominating in northern regions. Mixed-ploidy populations were common (46.9%).
      Principal components analysis and partial linear regression indicated that
      reduced summer precipitation and increased variation in diurnal and seasonal
      temperature range were significant predictors of the frequency of 9x plants in a
      population.* CONCLUSIONS: Results indicate that (1) geographic distribution of 6x
      and 9x individuals is nonrandom; (2) environmental variables are associated with
      cytotype distribution in A. gerardii; and (3) nearly half of populations surveyed
      include both 6x and 9x individuals. The persistence of mixed-ploidy populations
      may reflect a combination of recurrent polyploid formation and the prevalence of
      clonal reproduction.

PMID- 25587153
TI  - Sequoia maguanensis, a new Miocene relative of the coast redwood, Sequoia
      sempervirens, from China: implications for paleogeography and paleoclimate.
AB  - * PREMISE OF THE STUDY: The paleogeographical origin of the relict North American
      Sequoia sempervirens is controversial. Fossil records indicate a Neogene origin
      for its foliage characteristics. Although several fossils from the Miocene
      sediments in eastern Asia have been considered to have close affinities with the
      modern S. sempervirens, they lack the typical features of a leafy twig bearing
      linear as well as scale leaves, and the fertile shoots terminating by a cone. The
      taxonomic status of these fossils has remained unclear.* METHODS: New better
      preserved fossils from the upper Miocene of China indicate a new species of
      Sequoia. This finding not only confirms the former presence of this genus in
      eastern Asia, but it also confirms the affinity of this Asian form to the modern
      relict S. sempervirens.* KEY RESULTS: The principal foliage characteristics of S.
      sempervirens had already originated by the late Miocene. The eastern Asian
      records probably imply a Beringian biogeographic track of the ancestor of S.
      sempervirens in the early Neogene, at a time when the land bridge was not too
      cool for this thermophilic conifer to spread between Asia and North America.*
      CONCLUSIONS: The climatic context of the new fossil Sequoia in Southeast Yunnan,
      based on other floristic elements of the fossil assemblage in which it is found,
      is presumed to be warm and humid. Following the uplift of the Qinghai-Tibet
      Plateau, this warm, humid climate was replaced by the present monsoonal climate
      with dry winter and spring. This change may have led to the disappearance of this
      hygrophilous conifer from eastern Asia.

PMID- 25587154
TI  - Analysis of nuclear microsatellites reveals limited differentiation between
      Colchic and Hyrcanian populations of the wind-pollinated relict tree Zelkova
      carpinifolia (Ulmaceae).
AB  - * PREMISE OF THE STUDY: The Caucasus represents one of the world's biodiversity
      hotspots and includes the climatic refugia Hyrcan on the southern coast of the
      Caspian Sea and Colchis on the eastern coast of the Black Sea, where different
      species survived during the Quaternary climatic oscillations. We evaluated the
      genetic diversity of the relict tree Zelkova carpinifolia shared between the two
      refugia and distributed throughout the Caucasus and adjacent areas.* METHODS:
      Specimens were collected from 30 geographical sites in Azerbaijan, Georgia, Iran,
      and Turkey and screened for variability at eight nuclear microsatellite loci. The
      genetic diversity among and within populations was assessed using a set of
      statistical measures.* KEY RESULTS: We detected 379 different genotypes from a
      total of 495 individuals with varying degrees of clonal reproduction at the
      different sites. Low to intermediate levels of genetic diversity were observed at
      all sites, and strong differentiation between sampling sites was absent. In
      addition, we observed no clear genetic differentiation between the Colchis and
      Hyrcan. Bayesian clustering of the genotypes revealed three populations with high
      levels of admixture between the sampling sites.* CONCLUSIONS: The lack of strong
      genetic structure of studied populations of Z. carpinifolia contrasts with a
      previous study based on chloroplast markers and suggests that long-distance
      pollen dispersal is an important factor of gene flow among populations of Z.
      carpinifolia. The present study does not reveal any particular site with
      particularly isolated genotypes that would deserve more attention for
      conservation purposes than others, although some sites should be considered for
      further investigation.

PMID- 25587155
TI  - The potential for crop to wild hybridization in eggplant (Solanum melongena;
      Solanaceae) in southern India.
AB  - * PREMISE OF THE STUDY: In India and elsewhere, transgenic Bt eggplant (Solanum
      melongena) has been developed to reduce insect herbivore damage, but published
      studies of the potential for pollen-mediated, crop- to- wild gene flow are scant.
      This information is useful for risk assessments as well as in situ conservation
      strategies for wild germplasm.* METHODS: In 2010-2014, we surveyed 23 populations
      of wild/weedy eggplant (Solanum insanum; known as wild brinjal), carried out hand
      pollination experiments, and observed pollinators to assess the potential for
      crop- to- wild gene flow in southern India.* KEY RESULTS: Wild brinjal is a
      spiny, low-growing perennial commonly found in disturbed sites such as roadsides,
      wastelands, and sparsely vegetated areas near villages and agricultural fields.
      Fourteen of the 23 wild populations in our study occurred within 0.5 km of
      cultivated brinjal and at least nine flowered in synchrony with the crop. Hand
      crosses between wild and cultivated brinjal resulted in seed set and viable F1
      progeny. Wild brinjal flowers that were bagged to exclude pollinators did not set
      fruit, and fruit set from manual self-pollination was low. The exserted stigmas
      of wild brinjal are likely to promote outcrossing. The most effective pollinators
      appeared to be bees (Amegilla, Xylocopa, Nomia, and Heterotrigona spp.), which
      also were observed foraging for pollen on crop brinjal.* CONCLUSION: Our findings
      suggest that hybridization is possible between cultivated and wild brinjal in
      southern India. Thus, as part of the risk assessment process, we assume that
      transgenes from the crop could spread to wild brinjal populations that occur
      nearby.

PMID- 25587156
TI  - Genetic diversity and population structure of wild/weedy eggplant (Solanum
      insanum, Solanaceae) in southern India: implications for conservation.
AB  - * PREMISE OF THE STUDY: Crop wild relatives represent important genetic resources
      for crop improvement and the preservation of native biodiversity. Eggplant
      (Solanum melongena), known as brinjal in India, ranks high among crops whose wild
      gene pools are underrepresented in ex situ collections and warrant urgent
      conservation. Knowledge of outcrossing rates and patterns of genetic variation
      among wild populations can aid in designing strategies for both in situ and ex
      situ preservation.* METHODS: We used 14 microsatellite (simple sequence repeat)
      markers to examine genetic diversity, population structure, and outcrossing in 10
      natural populations of wild/weedy eggplant (S. insanum = S. melongena var.
      insanum) and three cultivated populations in southern India.* KEY RESULTS:
      Multilocus FST analyses revealed strong differentiation among populations and
      significant isolation by distance. Bayesian model-based clustering, principal
      coordinate analysis, and hierarchical cluster analysis grouped the wild/weedy
      populations into three major clusters, largely according to their geographic
      origin. The three crop populations were similar to each other and grouped with
      two wild/weedy populations that occurred nearby. Outcrossing rates among the
      wild/weedy populations ranged from 5-33%, indicating a variable mixed-mating
      system.* CONCLUSION: Geographic isolation has played a significant role in
      shaping the contemporary patterns of genetic differentiation among these
      populations, many of which represent excellent candidates for in situ
      conservation. In two cases, close genetic affinity between cultivars and nearby
      wild/weedy populations suggests that gene flow has occurred between them. To our
      knowledge, this is the first study investigating population-level patterns of
      genetic diversity in wild relatives of eggplant.

PMID- 25587157
TI  - The roles of history and ecology in chloroplast phylogeographic patterns of the
      bird-dispersed plant parasite Phoradendron californicum (Viscaceae) in the
      Sonoran Desert.
AB  - * PREMISE OF THE STUDY: A recurrent explanation for phylogeographic
      discontinuities in the Baja California Peninsula and the Sonoran Desert Region
      has been the association of vicariant events with Pliocene and Pleistocene seaway
      breaks. Nevertheless, despite its relevance for plant dispersal, other
      explanations such as ecological and paleoclimatic factors have received little
      attention. Here, we analyzed the role of several of these factors to describe the
      phylogeographic patterns of the desert mistletoe, Phoradendron californicum.*
      METHODS: Using noncoding chloroplast regions, we assess the marginal probability
      of 19 a priori hypotheses related to geological and ecological factors to predict
      the cpDNA variation in P. californicum using a Bayesian coalescent framework.
      Complementarily, we used the macrofossil record and niche model projections on
      Last Glacial Maximum climatic conditions for hosts, mistletoe, and a bird
      specialist to interpret phylogeographic patterns.* KEY RESULTS: Genealogical
      reconstructions revealed five clades, which suggest a combination of cryptic
      divergence, long-distance seed dispersal, and isolating postdivergence events.
      Bayesian hypothesis test favored a series of Pliocene and Pleistocene geological
      events related to the formation of the Baja California Peninsula and seaways
      across the peninsula as the most supported explanation for this genealogical
      pattern. However, age estimates, niche projections, and fossil records show
      dynamic host-mistletoe interactions and evidence of host races, indicating that
      ecological and geological factors have been interacting during the formation and
      structuring of phylogeographic divergence.* CONCLUSIONS: Variation in cpDNA
      across the species range results from the interplay of vicariant events, past
      climatic oscillations, and more dynamic factors related to ecological processes
      at finer temporal and spatial scales.

PMID- 25587159
TI  - Neurally adjusted ventilatory assist improves patient-ventilator synchrony in a
      patient with tetanus and unstable diaphragmatic electrical activity.
AB  - A 79-y-old man with generalized tetanus was admitted to the ICU. A left-forearm
      wound was surgically debrided, and the wound was closed. On postoperative day 1,
      after the patient experienced opisthotonos and convulsions, endotracheal
      intubation was performed. Propofol and diazepam were infused but failed to stop
      the convulsions. Morphine, midazolam, dantrolene, and rocuronium were used to
      ameliorate the muscle spasms. Magnesium sulfate was also infused. On
      postoperative day 15, patient-ventilator asynchrony was apparent. The patient
      showed recurrent tachypnea and bradypnea, which seemed typical of Cheyne-Stokes
      respiration. A neurally adjusted ventilatory assist (NAVA) catheter was inserted
      transnasally, and electrical activity of the diaphragm (Edi) was monitored.
      Readings showed regular attempts to breathe at 40-50 breaths/min with periodic
      changes in Edi amplitude. NAVA mode improved patient-ventilator synchrony.
      Periodic breathing continued for 2 weeks. We stopped monitoring Edi on
      postoperative day 39. He began respiratory rehabilitation and was transferred to
      a hospital for rehabilitation on postoperative day 80. We encountered periodic
      respiration in a patient with tetanus. Edi monitoring revealed periodic amplitude
      change. The cause of the periodic breathing pattern in this patient could not be
      determined but may be attributable to side effects of the pharmacologic
      interventions or the natural history of the disease itself. NAVA mode improved
      patient-ventilator synchrony. 

PMID- 25587160
TI  - Evaluation of an oxygen mask-based capnometry device in subjects extubated after
      abdominal surgery.
AB  - BACKGROUND: For early detection of respiratory and hemodynamic changes during
      anesthesia, continuous end-tidal carbon dioxide concentration (PETCO2) is
      monitored by capnometry. However, the accuracy of CO2 monitoring during
      spontaneous breathing in extubated patients remains undetermined. Therefore, we
      aimed to compare P(ETCO2) measured by capnometry using an oxygen mask with a
      carbon dioxide sampling port (capnometry-type oxygen mask) and P(CO2) in
      extubated subjects who had undergone abdominal surgery. Furthermore, we
      investigated whether spontaneous deep breathing affected dissociation between
      P(aCO2) and P(ETCO2). METHODS: Adult post-abdominal surgery subjects admitted to
      the ICU were enrolled in this study. After extubation, oxygen was supplied at 6
      L/min using the capnometry-type oxygen mask. After 30 min of oxygen supply,
      P(aCO2) blood gas analysis was performed, and P(ETCO2) was measured under resting
      and deep-breathing conditions. For both resting and deep-breathing conditions,
      the correlation between P(aCO2) and P(ETCO2) was analyzed. Furthermore, bias,
      precision, and limits of agreement were calculated using the Bland-Altman method.
      RESULTS: Twenty-five subjects (15 men, 10 women) with a mean age of 62 y
      (interquartile range of 57-76 y) and body mass index of 20-24 kg/m(2) were
      studied. The correlation (r) between P(aCO2) and P(ETCO2) under resting and deep
      breathing conditions was 0.50 and 0.56, respectively. Compared with P(aCO2), the
      bias and limits of agreement were -12.6 (-20.6 to -4.6) for resting P(ETCO2) and 
      9.1 (-16.0 to -2.1) for deep-breathing P(ETCO2). The association between P(aCO2)
      and deep-breathing P(ETCO2) was significantly smaller compared with resting
      P(ETCO2) (P = .002). CONCLUSIONS: It is possible to measure the P(ETCO2) under
      varying breathing conditions with the capnometry-type oxygen mask in subjects
      receiving oxygen supplementation after extubation following upper abdominal
      surgery to determine whether they are properly ventilating. (ClinicalTrials.gov
      registration UMIN000011925.).

PMID- 25587161
TI  - Muscle impairment in neuromuscular disease using an expiratory/inspiratory
      pressure ratio.
AB  - BACKGROUND: Neuromuscular diseases (NMDs) lead to different weakness patterns,
      and most patients with NMDs develop respiratory failure. Inspiratory and
      expiratory muscle strength can be measured by maximum static inspiratory pressure
      (PImax) and maximum static expiratory pressure (PEmax), and the relationship
      between them has not been well described in healthy subjects and subjects with
      NMDs. Our aim was to assess expiratory/inspiratory muscle strength in NMDs and
      healthy subjects and calculate PEmax/PImax ratio for these groups. METHODS:
      Seventy (35 males) subjects with NMDs (amyotrophic lateral sclerosis, myasthenia
      gravis, and myotonic dystrophy), and 93 (47 males) healthy individuals 20-80 y of
      age were evaluated for anthropometry, pulmonary function, PImax, and PEmax,
      respectively. RESULTS: Healthy individuals showed greater values for PImax and
      PEmax when compared with subjects with NMDs. PEmax/PImax ratio for healthy
      subjects was 1.31 +/- 0.26, and PEmax%/PImax% was 1.04 +/- 0.05; for subjects
      with NMDs, PEmax/PImax ratio was 1.45 +/- 0.65, and PEmax%/PImax% ratio was 1.42
      +/- 0.67. We found that PEmax%/PImax% for myotonic dystrophy was 0.93 +/- 0.24,
      for myasthenia gravis 1.94 +/- 0.6, and for amyotrophic lateral sclerosis 1.33 +/
      0.62 when we analyzed them separately. All healthy individuals showed higher
      PEmax compared with PImax. For subjects with NMDs, the impairment of PEmax and
      PImax is different among the 3 pathologies studied (P < .001). CONCLUSIONS:
      Healthy individuals and subjects with NMDs showed higher PEmax in comparison to
      PImax regarding the PEmax/PImax ratio. Based on the ratio, it is possible to
      state that NMDs show different patterns of respiratory muscle strength loss.
      PEmax/PImax ratio is a useful parameter to assess the impairment of respiratory
      muscles in a patient and to customize rehabilitation and treatment.

PMID- 25587162
TI  - A comparison of metered-dose inhaled albuterol versus endotracheal liquid bolus
      albuterol for the treatment of bronchoconstriction.
AB  - INTRODUCTION: Aerosolized albuterol delivery is a mainstay treatment for
      bronchoconstriction; however, almost no data exist that evaluate the clinical
      outcome of instillation of an endotracheal liquid bolus (ELB) of a bronchodilator
      directly into the airway. METHODS: This randomized trial sought to evaluate the
      efficacy of albuterol lavage via artificial airway with accompanied patient
      positioning. Subjects receiving mechanical ventilation for acute respiratory
      failure with clinical manifestations of bronchoconstriction were assigned to
      initially receive either traditional albuterol via metered-dose inhaler (MDI) or
      albuterol via ELB lavage with follow-up administration of the other therapy after
      a 4-h washout period. Clinical data were collected at baseline and at 5 and 30
      min post-treatment. RESULTS: Fourteen subjects (5 males, 9 females; mean age of
      57.5 y) were included in this study. In the group receiving initial ELB, peak
      airway pressure decreased significantly (P = .02), and a significant decrease in
      airway resistance mean scores was seen from baseline to 30 min post-treatment (P
      < .001) and from 5 to 30 min post-treatment (P = .003), with no significant
      effects seen with follow-up MDI. In the initial MDI treatment group, no
      significant effect on peak airway pressure or airway resistance was noted. S(pO2)
      increased at 5 min post-treatment with ELB. In contrast, S(pO2) decreased 30 min
      post-treatment with MDI. Mean arterial pressure decreased post-treatment with
      ELB. The pattern in heart rate change post-treatment with ELB was similar to that
      post-treatment with MDI, with a significant increase at the 5-min interval from
      baseline (P < .01), followed by a significant decrease at the 30-min interval (P
      < .001). There were no differences in dynamic compliance at each time interval
      following administration of both the MDI (P = .92) and ELB conditions (P = .18).
      CONCLUSIONS: ELB albuterol lavage may be a viable option to reverse
      bronchoconstriction in intubated patients with limited response to traditional
      aerosolized albuterol via MDI.

PMID- 25587163
TI  - Spirometry quality in adults with very severe lung function impairment.
AB  - BACKGROUND: Some technologists worry that patients with very severe lung disease
      are unable to complete several spirometry maneuvers, which require considerable
      effort. METHODS: We retrospectively selected all spirometry tests with an FEV1 <
      35% predicted done by adult subjects sent to our pulmonary function laboratory
      during a 3-y period. We determined the rates and correlates of poor quality test
      sessions. RESULTS: Approximately 90% of the tests done by the 558 subjects with
      very severe lung-function impairment (of > 30,000 subjects tested during the 3-y
      period) had adequate quality spirometry. Subjects with airway obstruction were
      less likely to meet FVC repeatability goals. A poor spirometry quality grade was
      associated with a very low FVC and a low body mass index, but not older age.
      CONCLUSIONS: Severe lung disease should not be used as an excuse for not meeting
      spirometry quality goals.

PMID- 25587164
TI  - Clinical predictors of obesity hypoventilation syndrome in obese subjects with
      obstructive sleep apnea.
AB  - BACKGROUND: Arterial blood gas (ABG) analysis is not a routine test in sleep
      laboratories due to its invasive nature. Therefore, the diagnosis of obesity
      hypoventilation syndrome (OHS) is underestimated. We aimed to evaluate the
      differences in subjects with OHS and pure obstructive sleep apnea (OSA) and to
      determine clinical predictors of OHS in obese subjects. METHODS: Demographics,
      body mass index (BMI), Epworth Sleepiness Scale score, polysomnographic data,
      ABG, spirometric measurements, and serum bicarbonate levels were recorded.
      RESULTS: Of 152 obese subjects with OSA (79 females/73 males, mean age of 50.3 +/
      10.6 y, BMI of 40.1 +/- 5.6 kg/m(2), 51.9% with severe OSA), 42.1% (n = 64) had
      OHS. Subjects with OHS had higher BMI (P = .02), neck circumference (P < .001),
      waist circumference (P < .001), waist/hip ratio (P = .02), Epworth Sleepiness
      Scale scores (P = .036), ABG and serum bicarbonate levels (P < .001), apnea
      hypopnea index (P = .01), oxygen desaturation index (P < .001), and total sleep
      time with S(pO2) < 90% (P < .001) compared with subjects with pure OSA (n = 88).
      They also had lower daytime PaO2 (P < .001), sleep efficiency (P = .032), mean
      S(pO2) (P < .001), and nadir S(pO2) (P < .001). Serum bicarbonate levels and
      nadir S(pO2) were the only independent predictive factors for OHS. A serum
      bicarbonate level of >= 27 mmol/L as the cutoff gives a satisfactory
      discrimination for the diagnosis of OHS (sensitivity of 76.6%, specificity of
      74.6%, positive predictive value of 54.5%, negative predictive value of 88.9%). A
      nadir S(pO2) of < 80% as the cutoff gives a satisfactory discrimination for the
      diagnosis of OHS (sensitivity of 82.8%, specificity of 54.5%, positive predictive
      value of 56.9%, negative predictive value of 81.4%). When we used a serum
      bicarbonate level of >= 27 mmol/L and/or a nadir S(pO2) of < 80% as a screening
      measure, only 3 of 64 subjects with OHS were missed. CONCLUSIONS: Serum
      bicarbonate level and nadir saturation were independent predictive factors for
      the diagnosis of OHS.

PMID- 25587165
TI  - Successful Colchicine Therapy in a Patient With Follicular Bronchiolitis Presumed
      to Be Asthma.
AB  - Follicular bronchiolitis (FB) is a rare small-airway pathology that is associated
      mainly with connective tissue diseases. This case report presents a new,
      diagnosed, different airway disease in a non-smoker with rheumatoid arthritis in
      remission who was treated for presumed asthma, but was not controlled. She was
      ultimately diagnosed with FB after video-assisted thoracoscopic surgery. The
      clinical findings of FB were controlled successfully by colchicine after she did
      not respond to systemic steroid therapy. This is the first case report of FB
      associated with rheumatoid arthritis that responded to colchicine. 

PMID- 25587166
TI  - Pneumothoraces Post Mechanical Cardiopulmonary Resuscitation: A Case Series.
AB  - The incidence of pneumothoraces with automated cardiopulmonary resuscitation
      (CPR) is unknown. Herein, we present 4 cases of pneumothoraces occurring in the
      setting of automated mechanical CPR (AM-CPR) in a 2-month period since
      incorporating mechanical devices into our resuscitation program. Two of the cases
      were in-hospital cardiac arrests, whereas the other 2 were out-of-hospital
      cardiac arrests. The Life-Stat 1008 device was utilized for AM-CPR in all cases.
      All cases demonstrated confirmed pneumothoraces on post-resuscitation imaging.
      Several factors may have contributed to the observed pneumothoraces. Two of the
      cases presented with obstructive lung disease, whereas the other 2 had underlying
      malignancy. Suboptimal positioning and failure to secure the included shoulder
      straps could have led to migration of the piston over the ribs. Further study is
      needed to determine the incidence of complications for all FDA-approved AM-CPR
      devices compared with manual chest compressions. 

PMID- 25587167
TI  - In Vitro Evaluation of Aerosols Delivered via the Nasal Route.
AB  - BACKGROUND: Infants and young children are obligate nose breathers; therefore, a
      transnasal route seems the logical delivery method of inhaled aerosols. The
      efficiency of aerosol delivery depends on several factors, such as interface,
      type of nebulizer, and patient age and breathing pattern. We hypothesized that
      the use of a vibrating mesh nebulizer, a tight-fitting face mask, and a head
      model and breathing pattern of an older child would result in a higher lung dose.
      We also hypothesized that the use of an anatomically correct model would more
      accurately reflect lung dose than models that do not include airways. METHODS: A
      model comprising a breathing simulator and an anatomically correct model of a 7
      month-old infant and a 5-y-old child with an interposed collection filter (lung
      dose) were used. Breathing patterns of a newborn, infant, and child were used
      with 7 interfaces. A continuous output and a vibrating mesh nebulizer were loaded
      with albuterol sulfate solution (5 mg/3.5 mL) and operated for 5 min. Albuterol
      mass was determined via spectrophotometer (276 nm). RESULTS: Lung dose varied
      between 0 and 3%. The jet nebulizer was more efficient than the vibrating mesh
      nebulizer. The front-loaded mask was the most efficient interface. We also found
      that higher tidal volumes were associated with higher lung doses and that the use
      of a larger airway model resulted in a lower lung dose. Finally, the model showed
      a good correlation with in vivo data and rendered lung doses severalfold lower
      than previous data obtained with oral models. CONCLUSIONS: Careful pairing of the
      aerosol generator and interface is very important during transnasal aerosol
      delivery.

PMID- 25587168
TI  - Diffuse Interstitial Pulmonary Infiltrates in Malignant Melanoma.
AB  - Only a few cases of sarcoidosis-like reaction to a pharmacologic compound have
      been reported in patients with melanoma in the literature. Long-term treatment
      with interferon alpha may be assumed. We report a case of a 25-y-old man who
      presented to our department with diffuse interstitial pulmonary infiltrates and
      slightly enlarged mediastinal lymph nodes as determined by computed tomography.
      He had a history of malignant melanoma with 18 months of interferon alpha-2
      therapy. Histological analysis of a transbronchial biopsy revealed sarcoidosis
      like reactions. 

PMID- 25587169
TI  - Systematic and endothelial inflammation and endothelial progenitor cell levels in
      emphysematous rats exposed to intermittent hypoxia.
AB  - BACKGROUND: This study aimed to develop an overlap syndrome rat model with
      intermittent hypoxia (IH) exposure as seen in obstructive sleep apnea, on a base
      of preexisting emphysema caused by 16 wk of smoke exposure to determine whether
      IH and emphysema existing simultaneously play overlapped roles on
      systematic/endothelial inflammation and endothelial damage. METHODS: Sixty male
      Wistar rats were divided into 4 groups of 15 each, labeled according to exposure
      conditions as control, IH, emphysema, and overlap groups. In these animals,
      electroencephalogram monitoring and preliminary experiments to obtain arterial
      blood gas values were performed. Serum concentrations of tumor necrosis factor
      (TNF)-alpha and interleukin (IL)-6, TNF-alpha and IL-6 concentrations in the
      culture medium, Ras homology A mRNA expression levels of endothelial cells from
      right common carotid artery, and ratio of carotid intima-media thickness of whole
      thickness of vascular wall expressed in percent (C-IMT) (%) values were
      evaluated. Subsequently, circulating endothelial progenitor cells (EPCs) within
      rat peripheral blood and bone marrow were measured with flow cytometry. RESULTS:
      The serum and endothelial concentrations of TNF-alpha and IL-6 and the levels of
      endothelial Ras homology A mRNA have statistically significant results described
      as overlap>emphysema>IH>control. The levels of EPCs in rat peripheral blood and
      bone marrow have statistically significant results described as
      overlap>IH>emphysema>control. C-IMT (%) values from right common carotid artery
      are the highest in the overlap group and the lowest in the control group. There
      is no statistical difference when comparing the IH and the emphysema groups.
      CONCLUSIONS: Regardless of whether IH and emphysema exposure are mechanistically
      synergistic, this overlap elicits a more severe systematic/endothelial
      inflammation and endothelial damage; meanwhile, a robust mobilization of EPCs is
      demonstrated, which is not to mean a robust adherent and repairing capability.

PMID- 25587170
TI  - Removal of the CPAP Therapy Device During Sleep and Its Association With Body
      Position Changes and Oxygen Desaturations.
AB  - BACKGROUND: Some patients with obstructive sleep apnea syndrome remove the CPAP
      device during sleep, although they start CPAP at bedtime. We hypothesized that
      body position changes and oxygen desaturations may be associated with patient
      removal of the CPAP device. METHODS: We consecutively enrolled 36 poor CPAP
      adherers and 25 good CPAP adherers. Body positions and oxygen desaturations were
      evaluated when these subjects used CPAP during sleep for 2 nights, permitting the
      removal of the CPAP device during the recording. RESULTS: Twelve poor CPAP
      adherers exhibited subject removal of the CPAP device within 4 h from the start
      of body position recording. The frequency of body position changes was
      significantly higher within 15 min before the CPAP removal than during other
      periods when CPAP was used. At the same time, oxygen desaturations were
      significantly more frequent within 15 min before CPAP removal than during other
      periods when CPAP was used. In addition, the majority (66.7%) of the CPAP removal
      events were followed by a change from a supine position to a non-supine position
      within 5 min. The number of body position changes during the first 4-h recording
      was significantly higher in the poor CPAP adherers who had removed their CPAP
      device compared with the poor CPAP adherers who had not removed their device.
      However, the number of body position changes or oxygen desaturation index under
      CPAP during the first 4-h recording was not significantly different between the
      poor CPAP adherers and good CPAP adherers. CONCLUSIONS: Our findings are the
      first to indicate associations among CPAP removal, body position changes, and
      oxygen desaturations during sleep in poor CPAP adherers. However, our findings
      also indicated that most good CPAP adherers make frequent body position changes
      without removal of CPAP device, suggesting that patients can adapt to the
      discomfort of CPAP therapy at the time of body position changes.

PMID- 25587171
TI  - Distractive Auditory Stimuli Alleviate the Perception of Dyspnea Induced by Low
      Intensity Exercise in Elderly Subjects With COPD.
AB  - BACKGROUND: Although recent studies have shown that distractive auditory stimuli
      (DAS) in the form of music increase adherence to exercise in subjects with COPD,
      the effect of DAS on dyspnea induced by low-intensity, constant-load exercise in
      elderly patients with COPD has not been elucidated. Therefore, the purpose of
      this study was to investigate the effect of DAS on the perception of dyspnea
      induced by low-intensity, constant-load exercise in elderly subjects with COPD.
      METHODS: We enrolled 16 male out-patients with COPD. Subjects completed cycling
      exercises with and without DAS at 40% maximum oxygen consumption. They were asked
      to rate their perception of dyspnea using the modified Borg scale every 3 min
      during exercise and every 1 min during the recovery period. RESULTS: Dyspnea
      perception during low-intensity exercise showed a significant correlation between
      the exercise condition (DAS and control) and exercise duration (P = .04).
      Exercise-induced dyspnea perception under the DAS condition was significantly
      lower than that under the control condition from 18 min after the start of
      exercise to 3 min after the end of exercise (18, 20, 21, 22, and 23 min, P = .01,
      P < .001, P = .009, P = .006, and P = .006, respectively). However, oxygen
      consumption and ventilation in response to low-intensity exercise did not
      significantly differ in the DAS and control conditions (P = .39 and .14,
      respectively) CONCLUSIONS: Our results suggest that DAS is a non-pharmacologic
      therapy that can be used to reduce the dyspneic sensation in elderly patients
      with COPD.

PMID- 25587172
TI  - Influence of ambient music on perceived exertion during a pulmonary
      rehabilitation session: a randomized crossover study.
AB  - BACKGROUND: Pulmonary rehabilitation is a key element in the treatment of COPD.
      Music has been shown to have a positive effect on parameters related to a
      decrease in exercise tolerance. The aim of this study was to evaluate the effect
      of listening to ambient music on perceived exertion during a pulmonary
      rehabilitation session for COPD subjects. METHODS: COPD subjects randomly
      performed a session of pulmonary rehabilitation with or without ambient music.
      Perceived exertion (Borg scales), anxiety (Hospital Anxiety and Depression Scale
      Anxiety Subscale), dyspnea (visual analog scale), and cardiorespiratory
      parameters were compared at the end of both sessions. RESULTS: Forty-one subjects
      were analyzed. The characteristics of the COPD subjects were as follows: age,
      70.5 +/- 8.4 y; body mass index, 22.7 +/- 3.9 kg/m(2); and FEV1, 38.6 +/- 12.5 %
      predicted. Perceived exertion was not modified by ambient music, but anxiety was
      improved (P = .02). Dyspnea, fatigue and cardiorespiratory parameters were not
      influenced by music during a typical session of the pulmonary rehabilitation
      program. CONCLUSIONS: This study demonstrates that perceived exertion during one
      pulmonary rehabilitation session was not influenced by ambient music. However, a
      positive effect on anxiety was observed. (ClinicalTrials.gov registration
      NCT01833260.).

PMID- 25587173
TI  - Home mechanical ventilation in Canada: a national survey.
AB  - BACKGROUND: No comprehensive Canadian national data describe the prevalence of
      and service provision for ventilator-assisted individuals living at home, data
      critical to health-care system planning for appropriate resourcing. Our objective
      was to generate national data profiling service providers, users, types of
      services, criteria for initiation and monitoring, ventilator servicing
      arrangements, education, and barriers to home transition. METHODS: Eligible
      providers delivering services to ventilator-assisted individuals (adult and
      pediatric) living at home were identified by our national provider inventory and
      referrals from other providers. The survey was administered via a web link from
      August 2012 to April 2013. RESULTS: The survey response rate was 152/171 (89%).
      We identified 4,334 ventilator-assisted individuals: an estimated prevalence of
      12.9/100,000 population, with 73% receiving noninvasive ventilation (NIV) and 18%
      receiving intermittent mandatory ventilation (9% not reported). Services were
      delivered by 39 institutional providers and 113 community providers. We
      identified variation in initiation criteria for NIV, with polysomnography
      demonstrating nocturnal hypoventilation (57%), daytime hypercapnia (38%), and
      nocturnal hypercapnia (32%) as the most common criteria. Various models of
      ventilator servicing were reported. Most providers (64%) stated that caregiver
      competency was a prerequisite for home discharge; however, repeated competency
      assessment and retraining were offered by only 45%. Important barriers to home
      transition were: insufficient funding for paid caregivers, equipment, and
      supplies; a shortage of paid caregivers; and negotiating public funding
      arrangements. CONCLUSIONS: Ventilatory support in the community appears well
      established, with most individuals managed with NIV. Although caregiver
      competency is a prerequisite to discharge, ongoing assessment and retraining were
      infrequent. Funding and caregiver availability were important barriers to home
      transition.

PMID- 25587176
TI  - Chronic exposure of grandparents to poverty and body mass index trajectories of
      grandchildren: a prospective intergenerational study.
AB  - In this study, I used the growth curve model to examine the association between
      grandparents' (first generation (G1)) life-course exposure to chronic poverty and
      grandchildren's (third generation (G3)) body mass index (BMI; weight (kg)/height
      (m)(2)) growth trajectories. This association was estimated separately for male
      and female grandchildren. Analyses were based on prospective data from a US
      longitudinal survey, the Panel Study of Income Dynamics (1968-2011), and 2 of its
      supplemental studies: the Child Development Supplement (1997-2011) and the
      Transition into Adulthood Study (1997-2011). A prospectively enrolled nationally
      representative cohort of 2,613 G3 youth (1,323 male, 1,290 female) sampled in the
      2 supplemental studies was linked to 1,719 grandparents from the Panel Study of
      Income Dynamics core sample. Chronic exposure to poverty among grandparents was
      prospectively ascertained annually over a 30-year period prior to the collection
      of data on grandchildren. Findings suggested that grandparents' chronic poverty
      exposure was positively associated with the slope of the BMI trajectory among
      granddaughters (beta = 0.10, 95% confidence interval: 0.03, 0.17) but not among
      grandsons (beta = 0.02, 95% confidence interval: -0.04, 0.08). The association
      between grandparents' chronic poverty exposure and granddaughters' BMI growth
      slope remained even after controlling for parental (second generation (G2))
      socioeconomic status and BMI. 

PMID- 25587174
TI  - Urinary melatonin concentration and the risk of breast cancer in Nurses' Health
      Study II.
AB  - Experimental and epidemiologic data support a protective role for melatonin in
      breast cancer etiology, yet studies in premenopausal women are scarce. In a case
      control study nested within the Nurses' Health Study II cohort, we measured the
      concentration of melatonin's major urinary metabolite, 6-sulfatoxymelatonin
      (aMT6s), in urine samples collected between 1996 and 1999 among 600 breast cancer
      cases and 786 matched controls. Cases were predominantly premenopausal women who
      were diagnosed with incident breast cancer after urine collection and before June
      1, 2007. Using multivariable conditional logistic regression, we computed odds
      ratios and 95% confidence intervals. Melatonin levels were not significantly
      associated with total breast cancer risk (for the fourth (top) quartile (Q4) of
      aMT6s vs. the first (bottom) quartile (Q1), odds ratio (OR) = 0.91, 95%
      confidence interval (CI): 0.64, 1.28; Ptrend = 0.38) or risk of invasive or in
      situ breast cancer. Findings did not vary by body mass index, smoking status,
      menopausal status, or time between urine collection and diagnosis (all
      Pinteraction values >= 0.12). For example, the odds ratio for total breast cancer
      among women with <=5 years between urine collection and diagnosis was 0.74 (Q4
      vs. Q1; 95% CI: 0.45, 1.20; Ptrend = 0.09), and it was 1.20 (Q4 vs. Q1; 95% CI:
      0.72, 1.98; Ptrend = 0.70) for women with >5 years. Our data do not support an
      overall association between urinary melatonin levels and breast cancer risk.

PMID- 25587177
TI  - Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients
      in a dose-dependent manner: a population-based cohort study.
AB  - OBJECTIVE: SLE is associated with increased risk of diabetes mellitus. Treatment
      for SLE requires high-dose glucocorticoids that may worsen glucose homoeostasis.
      HCQ can reduce diabetes risk in RA. This study aimed to investigate the
      association of HCQ use and diabetes mellitus risk in SLE patients. METHODS: This
      nationwide, population-based cohort study was conducted using the Taiwan National
      Health Insurance Research Database. In the period 2001-10, 8628 newly diagnosed
      SLE patients were identified after excluding those with a previous diagnosis of
      RA, psoriasis or diabetes mellitus. Incidence of diabetes mellitus was identified
      as a new diagnostic code using a diabetes mellitus-specific medication. RESULTS:
      Two hundred and twenty-one newly diagnosed diabetes mellitus patients were
      identified among SLE patients (6795 had taken HCQ and 1833 had never taken HCQ),
      with an average follow-up period of 5.6 years. Compared with patients without HCQ
      treatment, the hazard ratio (HR) of diabetes mellitus in patients taking HCQ at a
      cumulative dose >=129 g was reduced [HR 0.26 (95% CI 0.18, 0.37), P < 0.001].
      Daily glucocorticoid >=10 mg prednisolone-equivalent dose was associated with
      increased risk of developing diabetes mellitus [HR 2.47 (95% CI 1.44, 4.23), P =
      0.001], which was minimized by concomitant HCQ use at a cumulative dose >=129 g.
      CONCLUSION: In SLE patients, the use of HCQ is associated with reduced risk of
      incident diabetes mellitus in a dose-dependent manner. High-dose glucocorticoids
      increase the risk of diabetes, which can be decreased by concomitant HCQ use.

PMID- 25587178
TI  - Does reduction of disease activity improve early markers of cardiovascular
      disease in newly diagnosed rheumatoid arthritis patients?
AB  - OBJECTIVE: The incidence of cardiovascular disease (CVD) is increased in RA. This
      study was designed to evaluate whether a reduction in disease activity influences
      early markers of CVD. METHODS: In a prospective longitudinal study, 58 newly
      diagnosed RA patients and 58 age- and sex-matched healthy controls (HCs) were
      included. Endothelial dysfunction was measured by small artery elasticity (SAE)
      and endothelial cell activation was assessed by measuring soluble vascular
      cellular activation molecule 1(sVCAM-1) and von Willebrand factor (vWF). Advanced
      glycation end products (AGEs) were quantified by skin autofluorescence. After 1
      year, measurements were repeated in all RA patients. RESULTS: At entry, SAE was
      decreased in RA vs HCs [median 3.4 ml/mmHg100 (range 1.2-9.0) vs 6.1 (range 5.0
      15.3), P < 0.0001] and sVCAM-1 and vWF were increased: 391 ng/ml (range 256-680)
      vs 341 (range 223-691) (P = 0.0015) and 120 ng/ml (range 26.5-342) vs 99 (range
      22-298) (P = 0.02), respectively. SAE was inversely correlated with the 28-joint
      DAS (DAS28; r = -0.31, P = 0.016). AGEs were increased by 2.55 arbitrary units
      (range 1.29-4.65) vs 2.12 (range 1.32-3.82) in HCs (P = 0.003). In multivariate
      analysis, the presence of RA, age and systolic blood pressure were independently
      and inversely related to SAE. After 1 year, SAE had significantly improved in RA,
      from 3.4 (range 1.2-9.0) to 3.8 (range 1.5-10.3) (P = 0.03). CONCLUSION:
      Endothelial dysfunction is present in newly diagnosed RA patients, independently
      of traditional risk factors and is inversely correlated with disease activity. By
      reducing disease activity, endothelial dysfunction improves, although not to
      normal values. Also, a reduction in disease activity targeting traditional risk
      factors remains important in preventing CVD in RA.

PMID- 25587179
TI  - IgG4-related periaortitis vs idiopathic periaortitis: is there a role for
      atherosclerotic plaque in the pathogenesis of IgG4-related periaortitis?
AB  - OBJECTIVE: The diagnosis of (isolated) IgG4-related periaortitis is often based
      on elevated serum IgG4 levels since in tissues such as the aorta, biopsies cannot
      be easily performed. However, the role for serum IgG4 as a biomarker for IgG4
      related periaortitis is indistinct. The main purpose of our study was to identify
      clinical differences between periaortitis with elevated vs normal serum IgG4
      levels. METHODS: A retrospective study was performed on 68 non-infectious
      periaortitis patients. We compared demographic, clinical, biochemical and
      radiological data in patients with elevated serum IgG4 levels with data from
      patients with normal serum IgG4 levels. The calcium content of the aortic wall
      was calculated to determine the amount of atherosclerosis. RESULTS: After
      applying exclusion criteria, our study population consisted of nine IgG4-related
      periaortitis patients and eight idiopathic periaortitis patients. Striking
      significant differences were male predominance (P = 0.001) and multifocal organ
      involvement (P = 0.004) in IgG4-related periaortitis patients compared with the
      idiopathic periaortitis group. The calcium content of the total aortic wall was
      significantly higher in IgG4-related periaortitis patients (P = 0.005). No other
      significant differences were found. CONCLUSION: Elevated serum IgG4 levels, male
      gender, a higher calcium content of the aortic wall and multifocal organ
      involvement are features that might provide a higher probability for IgG4-related
      periaortitis compared with idiopathic periaortitis. Our study results might be
      compatible with the hypothesis of Mitchinson and Parums that atherosclerotic
      plaque plays a role in the pathogenesis of chronic periaortitis.

PMID- 25587180
TI  - Structural basis for recognition of intron branchpoint RNA by yeast Msl5 and
      selective effects of interfacial mutations on splicing of yeast pre-mRNAs.
AB  - Saccharomyces cerevisiae Msl5 orchestrates spliceosome assembly by binding the
      intron branchpoint sequence 5'-UACUAAC and, with its heterodimer partner protein
      Mud2, establishing cross intron-bridging interactions with the U1 snRNP at the 5'
      splice site. Here we define the central Msl5 KH-QUA2 domain as sufficient for
      branchpoint RNA recognition. The 1.8 A crystal structure of Msl5-(KH-QUA2) bound
      to the branchpoint highlights an extensive network of direct and water-mediated
      protein-RNA and intra-RNA atomic contacts at the interface that illuminate how
      Msl5 recognizes each nucleobase of the UACUAAC element. The Msl5 structure
      rationalizes a large body of mutational data and inspires new functional studies
      herein, which reveal how perturbations of the Msl5.RNA interface impede the
      splicing of specific yeast pre-mRNAs. We also identify interfacial mutations in
      Msl5 that bypass the essentiality of Sub2, a DExD-box ATPase implicated in
      displacing Msl5 from the branchpoint in exchange for the U2 snRNP. These studies
      establish an atomic resolution framework for understanding splice site selection
      and early spliceosome dynamics. 

PMID- 25587181
TI  - Cross-sectional survey comparing HIV risk behaviours of adolescent and young
      adult men who have sex with men only and men who have sex with men and women in
      the U.S. and Puerto Rico.
AB  - OBJECTIVE: To examine the HIV risk behaviours of men who have sex with men only
      (MSMO) and men who have sex with men and women (MSMW), aged 12-24 years, in five
      US cities and in San Juan, Puerto Rico. METHODS: Data were collected through four
      annual cross-sectional anonymous surveys at community venues and included
      questions about sexual partnerships, sexual practices including condom use and
      substance use. Demographic and risk profiles were summarised for both groups.
      RESULTS: A total of 1198 men were included in this analysis, including 565 MSMO
      and 633 MSMW. There were statistically significant differences between the two
      groups for many risk factors examined in multivariable models. MSMW were more
      likely to identify as bisexual, be in a long-term relationship, have a history of
      homelessness, have ever used marijuana, have ever been tested for HIV and to have
      been tested for HIV within the past 6 months. MSMW may be more likely to ever
      exchange sex for money and ever have a sexually transmitted infection than MSMO.
      CONCLUSIONS: MSMW were more likely to report several markers of socioeconomic
      vulnerability or behaviours associated with increased risk for HIV than MSMO.
      MSMW contribute to HIV prevalence in the USA, and better understanding of the
      risk profile of this group is essential to understand heterosexual HIV
      transmission. MSMW, particularly those who identify as bisexual or questioning,
      may feel uncomfortable participating in programmes that are designed for gay
      identified men. Therefore, prevention strategies need to target distinct
      subgroups that compose the population of MSM.

PMID- 25587183
TI  - Distal femoral fracture after double-bundle anterior cruciate ligament
      reconstruction surgery.

PMID- 25587182
TI  - Measuring child awareness for adult symptomatic HIV using a verbal assessment
      tool: concordance between adult-child dyads on adult HIV-associated symptoms and
      illnesses.
AB  - OBJECTIVES: This study assessed children's awareness for adult HIV-associated
      symptoms and illnesses using a verbal assessment tool by analysing inter-rater
      reliability between adult-child dyads. This study also evaluated sociodemographic
      and household characteristics associated with child awareness of adult
      symptomatic HIV. METHODS: A cross-sectional survey using a representative
      community sample of adult-child dyads (N=2477 dyads) was conducted in KwaZulu
      Natal, South Africa. Analyses focused on a subsample (n=673 adult-child dyads)
      who completed verbal assessment interviews for symptomatic HIV. We used an
      existing validated verbal autopsy approach, originally designed to determine AIDS
      related deaths by adult proxy reporters. We adapted this approach for use by
      child proxy reporters for reporting on HIV-associated symptoms and illnesses
      among living adults. Analyses assessed whether children could reliably report on
      adult HIV-associated symptoms and illnesses and adult provisional HIV status.
      RESULTS: Adult-child pairs concurred above the 65th percentile for 9 of the 10
      HIV-associated symptoms and illnesses with sensitivities ranging from 10% to 100%
      and specificities ranging from 20% to 100%. Concordant reporting between adult
      child dyads for the adult's provisional HIV status was 72% (sensitivity=68%,
      specificity=73%). Children were more likely to reliably match adult's reports of
      provisional HIV status when they lived in households with more household members,
      and households with more robust socioeconomic indicators including access to
      potable water, food security and television. CONCLUSIONS: Children demonstrate
      awareness of HIV-associated symptoms and illnesses experienced by adults in their
      household. Children in households with greater socioeconomic resources and more
      household members were more likely to reliably report on the adult's provisional
      HIV status.

PMID- 25587184
TI  - Intra- and interobserver agreement in the classification and treatment of distal
      third clavicle fractures.
AB  - BACKGROUND: In treatment of distal third clavicle fractures, the Neer
      classification system, based on the location of the fracture in relation to the
      coracoclavicular ligaments, has traditionally been used to determine fracture
      pattern stability. PURPOSE: To determine the intra- and interobserver reliability
      in the classification of distal third clavicle fractures via standard plain
      radiographs and the intra- and interobserver agreement in the preferred treatment
      of these fractures. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 3.
      METHODS: Thirty radiographs of distal clavicle fractures were randomly selected
      from patients treated for distal clavicle fractures between 2006 and 2011. The
      radiographs were distributed to 22 shoulder/sports medicine fellowship-trained
      orthopaedic surgeons. Fourteen surgeons responded and took part in the study. The
      evaluators were asked to measure the size of the distal fragment, classify the
      fracture pattern as stable or unstable, assign the Neer classification, and
      recommend operative versus nonoperative treatment. The radiographs were reordered
      and redistributed 3 months later. Inter- and intrarater agreement was determined
      for the distal fragment size, stability of the fracture, Neer classification, and
      decision to operate. Single variable logistic regression was performed to
      determine what factors could most accurately predict the decision for surgery.
      RESULTS: Interrater agreement was fair for distal fragment size, moderate for
      stability, fair for Neer classification, slight for type IIB and III fractures,
      and moderate for treatment approach. Intrarater agreement was moderate for distal
      fragment size categories (kappa = 0.50, P < .001) and Neer classification (kappa
      = 0.42, P < .001) and substantial for stable fracture (kappa = 0.65, P < .001)
      and decision to operate (kappa = 0.65, P < .001). Fracture stability was the best
      predictor of treatment, with 89% accuracy (P < .001). CONCLUSION: Fracture
      stability determination and the decision to operate had the highest interobserver
      agreement. Fracture stability was the key determinant of treatment, rather than
      the Neer classification system or the size of the distal fragment.

PMID- 25587185
TI  - The prevalence and combined prevalences of anatomic factors associated with
      recurrent patellar dislocation: a magnetic resonance imaging study.
AB  - BACKGROUND: Anatomic factors, including patella alta, increased tibial tubercle
      trochlear groove (TT-TG) distance, rotational deformities, and trochlear
      dysplasia, are associated with dislocation of the patella. Identifying the
      presence of these anatomic factors both in isolation and in combination may
      influence treatment in patients with patellar dislocation. PURPOSE: The aim of
      this study was to compare the prevalence and combined prevalences of these
      anatomic factors using magnetic resonance imaging in a group of patients with and
      without histories of recurrent dislocation of the patella. STUDY DESIGN: Case
      control study; Level of evidence, 3. METHODS: The prevalence and combined
      prevalences of patella alta, increased TT-TG distance, rotational deformity, and
      trochlear dysplasia on magnetic resonance imaging were reported and compared in
      60 patients (60 knees) with and 120 patients (120 knees) without histories of
      recurrent patellar dislocation. RESULTS: Patients with recurrent patellar
      dislocation possessed higher rates of patella alta (60.0% vs. 20.8%), increased
      TT-TG distance (42.0% vs. 3.2%), rotational deformity (26.7% vs. 2.5%), and
      trochlear dysplasia (68.3% vs. 5.8%) compared with patients without histories of
      patellar dislocation. Multiple anatomic factors were identified in 58.3% of
      patients (35/60) with recurrent dislocation compared with only 1.7% of controls
      (2/120). CONCLUSION: Recurrent patellar dislocation is associated with an
      increased prevalence of patella alta, increased TT-TG distance, rotational
      deformity, and trochlear dysplasia compared with patients with no histories of
      patellar dislocation. Multiple anatomic factors were identified in the majority
      of patients with recurrent dislocation. Further research may identify which
      factors play a greater role in patellar stability and may allow physicians to
      predict which first-time dislocation patients are more likely to sustain
      recurrence.

PMID- 25587187
TI  - Characterization of size-specific particulate matter emission rates for a
      simulated medical laser procedure--a pilot study.
AB  - Prior investigation on medical laser interaction with tissue has suggested device
      operational parameter settings influence laser generated air contaminant
      emission, but this has not been systematically explored. A laboratory-based
      simulated medical laser procedure was designed and pilot tested to determine the
      effect of laser operational parameters on the size-specific mass emission rate of
      laser generated particulate matter. Porcine tissue was lased in an emission
      chamber using two medical laser systems (CO2, lambda = 10,600 nm; Ho:YAG, lambda
      = 2100 nm) in a fractional factorial study design by varying three operational
      parameters (beam diameter, pulse repetition frequency, and power) between two
      levels (high and low) and the resultant plume was measured using two real-time
      size-selective particle counters. Particle count concentrations were converted to
      mass emission rates before an analysis of variance was used to determine the
      influence of operational parameter settings on size-specific mass emission rate.
      Particle shape and diameter were described for a limited number of samples by
      collecting particles on polycarbonate filters, and photographed using a scanning
      electron microscope (SEM) to examine method of particle formation. An increase in
      power and decrease in beam diameter led to an increase in mass emission for the
      Ho:YAG laser at all size ranges. For the CO2 laser, emission rates were dependent
      on particle size and were not statistically significant for particle ranges
      between 5 and 10 um. When any parameter level was increased, emission rate of the
      smallest particle size range also increased. Beam diameter was the most
      influential variable for both lasers, and the operational parameters tested
      explained the most variability at the smallest particle size range. Particle
      shape was variable and some particles observed by SEM were likely created from
      mechanical methods. This study provides a foundation for future investigations to
      better estimate size-specific mass emission rates and particle characteristics
      for additional laser operational parameters in order to estimate occupational
      exposure, and to inform control strategies.

PMID- 25587186
TI  - What Is the Association Between Sports Participation and the Development of
      Proximal Femoral Cam Deformity? A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Femoroacetabular impingement (FAI) is recognized as a common cause of
      hip pain and intra-articular disorders in athletes. Studies have suggested a link
      between participation in athletics during adolescence and the development of cam
      type deformities of the proximal femoral head-neck junction. PURPOSE: To
      investigate the association of sporting activity participation during adolescence
      and the development of cam deformity. STUDY DESIGN: Systematic review. METHODS:
      The PubMed, EMBASE, and Cochrane databases were searched to identify potential
      studies. Abstracts and manuscripts (when applicable) were independently reviewed
      by 2 reviewers. Nine studies met the inclusion criteria, including 8 studies that
      compared the prevalence of cam deformity in athletes with that in controls and 3
      studies that compared the prevalence of cam deformity before and after physeal
      closure (2 with both). A meta-analysis was performed with pooling of data and
      random-effects modeling to compare rates of cam deformity between athletes and
      controls. RESULTS: High-level male athletes are 1.9 to 8.0 times more likely to
      develop a cam deformity than are male controls. The pooled prevalence rate (by
      hip) of cam deformity in male athletes was 41%, compared with 17% for male
      controls. The pooled mean alpha angle among male athletes was 61 degrees ,
      compared with 51 degrees  for male controls. CONCLUSION: Males participating in
      specific high-level impact sports (hockey, basketball, and possibly soccer) are
      at an increased risk of physeal abnormalities of the anterosuperior head-neck
      junction that result in a cam deformity at skeletal maturity.

PMID- 25587189
TI  - The mitotic checkpoint protein kinase BUB1 is an engine in the TGF-beta signaling
      apparatus.
AB  - The transforming growth factor-beta (TGF-beta) pathway mediates critical events
      in cell behavior that contribute to development and disease. The mitotic
      checkpoint guarantees faithful chromosomal segregation during cell division. In
      the 6 January 2015 issue of Science Signaling, Nyati et al. reported that the
      mitotic checkpoint kinase BUB1 promotes the activity of TGF-beta receptors, which
      adds new molecular links between these fundamental biological processes. 

PMID- 25587188
TI  - Extensive glycosylation of ACPA-IgG variable domains modulates binding to
      citrullinated antigens in rheumatoid arthritis.
AB  - OBJECTIVES: To understand the molecular features distinguishing anti
      citrullinated protein antibodies (ACPA) from 'conventional' antibodies in
      rheumatoid arthritis (RA). METHODS: Serum of ACPA-positive RA patients was
      fractionated by size exclusion chromatography and analysed for the presence of
      ACPA-IgG by ELISA. ACPA-IgG and non-citrulline-specific IgG were affinity
      purified from serum, plasma and/or synovial fluid and analysed by gel
      electrophoresis. Electrophoresis bands were excised, enzymatically digested and
      analysed by mass spectrometry. Binding affinity to citrullinated antigens was
      measured by ELISA and imaging surface plasmon resonance using recombinant
      monoclonal ACPA with molecular modifications. RESULTS: In all donor samples
      studied (n=24), ACPA-IgG exhibited a 10-20 kDa higher molecular weight compared
      with non-autoreactive IgG. This feature also distinguished ACPA-IgG from
      antibodies against recall antigens or other disease-specific autoantibodies.
      Structural analysis revealed that a high frequency of N-glycans in the
      (hyper)variable domains of ACPA is responsible for this observation. In line with
      their localisation, these N-glycans were found to modulate binding avidity of
      ACPA to citrullinated antigens. CONCLUSIONS: The vast majority of ACPA-IgG
      harbour N-glycans in their variable domains. As N-linked glycosylation requires
      glycosylation consensus sites in the protein sequence and as these are lacking in
      the 'germline-counterparts' of identified variable domains, our data indicate
      that the N-glycosylation sites in ACPA variable domains have been introduced by
      somatic hypermutation. This finding also suggests that ACPA-hyperglycosylation
      confers a selective advantage to ACPA-producing B cells. This unique and
      completely novel feature of the citrulline-specific immune response in RA
      elucidates our understanding of the underlying B cell response.

PMID- 25587190
TI  - STIM2 enhances receptor-stimulated Ca2+ signaling by promoting recruitment of
      STIM1 to the endoplasmic reticulum-plasma membrane junctions.
AB  - A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+)
      entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in
      endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response
      to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated
      activation of SOCE by promoting STIM1 clustering in ER-PM junctions at low
      stimulus intensities. Targeted deletion of STIM2 in mouse salivary glands
      diminished fluid secretion in vivo and SOCE activation in dispersed salivary
      acinar cells stimulated with low concentrations of muscarinic receptor agonists.
      STIM2 knockdown in human embryonic kidney (HEK) 293 cells diminished agonist
      induced Ca(2+) signaling and nuclear translocation of NFAT (nuclear factor of
      activated T cells). STIM2 lacking five carboxyl-terminal amino acid residues did
      not promote formation of STIM1 puncta at low concentrations of agonist, whereas
      coexpression of STIM2 with STIM1 mutant lacking the polybasic region STIM1DeltaK
      resulted in co-clustering of both proteins. Together, our findings suggest that
      STIM2 recruits STIM1 to ER-PM junctions at low stimulus intensities when ER
      Ca(2+) stores are mildly depleted, thus increasing the sensitivity of Ca(2+)
      signaling to agonists. 

PMID- 25587191
TI  - Annotation of human cancers with EGFR signaling-associated protein complexes
      using proximity ligation assays.
AB  - Strategies to measure functional signaling-associated protein complexes have the
      potential to augment current molecular biomarker assays, such as genotyping and
      expression profiling, used to annotate diseases. Aberrant activation of epidermal
      growth factor receptor (EGFR) signaling contributes to diverse cancers. We used a
      proximity ligation assay (PLA) to detect EGFR in a complex with growth factor
      receptor-bound protein 2 (GRB2), the major signaling adaptor for EGFR. We used
      multiple lung cancer cell lines to develop and characterize EGFR:GRB2 PLA and
      correlated this assay with established biochemical measures of EGFR signaling. In
      a panel of patient-derived xenografts in mice, the intensity of EGFR:GRB2 PLA
      correlated with the reduction in tumor size in response to the EGFR inhibitor
      cetuximab. In tumor biopsies from three cohorts of lung cancer patients, positive
      EGFR:GRB2 PLA was observed in patients with and without EGFR mutations, and the
      intensity of EGFR:GRB2 PLA was predictive of overall survival in an EGFR
      inhibitor-treated cohort. Thus, we established the feasibility of using PLA to
      measure EGFR signaling-associated protein complexes in patient-based materials,
      suggesting the potential for similar assays for a broader array of receptor
      tyrosine kinases and other key signaling molecules. 

PMID- 25587193
TI  - Rotational thromboelastometry in prediction of bleeding after cardiac surgery.
AB  - BACKGROUND: Reexploration and its associated complications significantly affect
      hospital mortality and morbidity. Therefore, to prevent postoperative bleeding
      and its related complications, using an appropriate modality is essential during
      cardiac surgery. METHODS: Four hundred patients (296 males and 104 females, mean
      age 60.8 +/- 9 years) scheduled for first-time coronary artery bypass graft
      surgery were prospectively enrolled. Blood samples were obtained for ROTEM
      testing before surgery and 30 min after heparin reversal. The patients were
      divided into 2 groups: group 1 was patients with no abnormal postoperative
      bleeding and group 2 was patients who required reexploration for abnormal
      postoperative bleeding. Group 2 patients were divided into 2 subgroups: 2a was
      patients with surgical bleeding and group 2b was patients with nonsurgical
      bleeding. Variables were compared between groups. RESULTS: Among the 400
      patients, 42 were reexplored. Hospital stay was significantly longer and hospital
      deaths more frequent in group 2 patients (p < 0.001 and p = 0.010, respectively).
      Ten (2.8%) patients had abnormal preoperative results of ROTEM in group 1
      compared to 14 (33.3%) in group 2 (p < 0.001). After surgery, the number of
      patients with abnormal ROTEM results was significantly different between the 2
      groups: 6 (1.7%) in group 1 vs. 14 (33.3%) in group 2 (p < 0.001). Four (12.5%)
      patients in group 2a had abnormal preoperative ROTEM results compared to 10
      (100%) in group 2a (p < 0.001). CONCLUSION: Measuring coagulation factors by
      ROTEM both before surgery and after heparin reversal can identify patients at
      increased risk of postoperative bleeding.

PMID- 25587195
TI  - Effects of disturbance on vegetation by sand accretion and erosion across coastal
      dune habitats on a barrier island.
AB  - Coastal geomorphology and vegetation are expected to be particularly sensitive to
      climate change, because of disturbances caused by sea-level rise and increased
      storm frequency. Dunes have critical reciprocal interactions with vegetation;
      dunes create habitats for plants, while plants help to build dunes and promote
      geomorphological stability. These interactions are also greatly affected by
      disturbances associated with sand movement, either in accretion (dune building)
      or in erosion. The magnitude and intensity of disturbances are expected to vary
      with habitat, from the more exposed and less stable foredunes, to low-lying and
      flood-prone interdunes, to the protected and older backdunes. Permanent plots
      were established at three different spatial scales on St George Island, FL, USA,
      where the vegetation and dune elevation were quantified annually from 2011 to
      2013. Change in elevation, either through accretion or erosion, was used as a
      measure of year-to-year disturbance over the 2 years of the study. At the scale
      of different dune habitats, foredunes were found to have the greatest
      disturbance, while interdunes had the least. Elevation and habitat (i.e.
      foredune, interdune, backdune) were significantly correlated with plant community
      composition. Generalized linear models conducted within each habitat show that
      the change in elevation (disturbance) is also significantly correlated with the
      plant community, but only within foredunes and interdunes. The importance of
      disturbance in exposed foredunes was expected and was found to be related to an
      increasing abundance of a dominant species (Uniola paniculata) in eroding areas.
      The significant effect of disturbance in the relatively stable interdunes was
      surprising, and may be due to the importance of flooding associated with small
      changes in elevation in these low-lying areas. Overall, this study documents
      changes in the plant community associated with elevation, and demonstrates that
      the foredune and interdune communities are also associated with the responses of
      specific species to local changes in elevation due to accretion or erosion. 

PMID- 25587194
TI  - Influence of sulfur and cadmium on antioxidants, phytochelatins and growth in
      Indian mustard.
AB  - Soils in many parts of the world are contaminated with heavy metals, leading to
      multiple, deleterious effects on plants and threats to world food production
      efficiency. Cadmium (Cd) is one such metal, being toxic at relatively low
      concentrations as it is readily absorbed and translocated in plants. Sulfur-rich
      compounds are critical to the impact of Cd toxicity, enabling plants to increase
      their cellular defence and/or sequester Cd into vacuoles mediated by
      phytochelatins (PCs). The influence of sulfur on Cd-induced stress was studied in
      the hyperaccumulator plant Indian mustard (Brassica juncea) using two sulfur
      concentrations (+S, 300 uM [Formula: see text] and S-deficient -S, [Formula: see
      text]) with and without the addition of Cd (100 uM CdCl2) at two different time
      intervals (7 and 14 days after treatment). Compared with control plants (+S/-Cd),
      levels of oxidative stress were higher in S-deficient (-S/-Cd) plants, and
      greatest in S-deficient Cd-treated (-S/+Cd) plants. However, additional S
      (+S/+Cd) helped plants cope with oxidative stress. Superoxide dismutase emerged
      as a key player against Cd stress under both -S and +S conditions. The activity
      of ascorbate peroxidase, glutathione reductase and catalase declined in Cd
      treated and S-deficient plants, but was up-regulated in the presence of sulfur.
      Sulfur deficiency mediated a decrease in ascorbate and glutathione (GSH) content
      but changes in ascorbate (reduced : oxidized) and GSH (reduced : oxidized) ratios
      were alleviated by sulfur. Our data clearly indicate that a sulfur pool is needed
      for synthesis of GSH, non-protein thiols and PCs and is also important for
      growth. Sulfur-based defence mechanisms and the cellular antioxidant pathway,
      which are critical for tolerance and growth, collapsed as a result of a decline
      in the sulfur pool. 

PMID- 25587192
TI  - MAPK feedback encodes a switch and timer for tunable stress adaptation in yeast.
AB  - Signaling pathways can behave as switches or rheostats, generating binary or
      graded responses to a given cell stimulus. We evaluated whether a single
      signaling pathway can simultaneously encode a switch and a rheostat. We found
      that the kinase Hog1 mediated a bifurcated cellular response: Activation and
      commitment to adaptation to osmotic stress are switchlike, whereas protein
      induction and the resolution of this commitment are graded. Through
      experimentation, bioinformatics analysis, and computational modeling, we
      determined that graded recovery is encoded through feedback phosphorylation and a
      gene induction program that is both temporally staggered and variable across the
      population. This switch-to-rheostat signaling mechanism represents a versatile
      stress adaptation system, wherein a broad range of inputs generate an "all-in"
      response that is later tuned to allow graded recovery of individual cells over
      time. 

PMID- 25587196
TI  - Fluorosis and periostitis deformans as complications of prolonged voriconazole
      treatment.
AB  - We describe a case of development of painful periostitis deformans in a 39-year
      old woman who was receiving long-term voriconazole treatment for Aspergillus
      infection as a complication of orthotopic liver transplant. Measurement of
      fluoride levels strongly supports fluorosis to be the mechanism of the
      voriconazole-induced periostitis deformans and supports the concept that such
      measurements might be of use in predicting this complication of long-term
      voriconazole treatment. 

PMID- 25587197
TI  - Plasma capric acid concentrations in healthy subjects determined by high
      performance liquid chromatography.
AB  - BACKGROUND: Capric acid (FA10:0, decanoic acid) is a medium-chain fatty acid
      abundant in tropical oils such as coconut oil, whereas small amounts are present
      in milk of goat, cow, and human. Orally ingested FA10:0 is transported to the
      liver and quickly burnt within it. Only few reports are available for FA10:0
      concentrations in human plasma. METHODS: Fasting (n = 5, male/female = 3/2, age
      31 +/- 9.3 years old) and non-fasting (n = 106, male/female = 44/62, age 21.9 +/-
      3.2 years old) blood samples were collected from apparently healthy Japanese
      volunteers. The total FA10:0 in the plasma were measured by high-performance
      liquid chromatography after derivatization with 2-nitrophenylhydrazine followed
      by UV detection. RESULTS: Inter and intra-assay coefficient of variation of
      FA10:0 assay at three different concentrations ranged in 1.7-3.9 and 1.3-5.4%,
      respectively, with an analytical recovery of 95.2-104.0%. FA10:0 concentration
      was below detection limit (0.1 umol/L) in each fasting human plasma. FA10:0 was
      not detected in 50 (47.2%) of 106 non-fasting blood samples, while 29 (27.4%)
      plasma samples contained FA10:0 less than or equal to 0.5 umol/L (0.4 +/- 0.1),
      and 27 (25.5%) contained it at more than 0.5 umol/L (0.9 +/- 0.3). CONCLUSION: A
      half of the non-fasting plasma samples contained detectable FA10:0. This simple,
      precise, and accurate high-performance liquid chromatography method might be
      useful for monitoring plasma FA10:0 during medium-chain triglycerides therapy.

PMID- 25587198
TI  - The interference by HbF on HbA1c (BM Test HbA1c) measurement in enzymatic method.
AB  - BACKGROUND: High performance liquid chromatography and immunological and
      enzymatic methods are known as the methods for HbA1c measurement. However, the
      differences in the principles of the methods may cause slight discrepancies,
      which become problems especially in the regions where hemoglobinopathies that
      have high HbF concentrations are commonly seen. In this report, we discuss the
      effect of HbF on the HbA1c measurement by the enzymatic method (BM Test HbA1c)
      which can be applied to automatic analyzer of high sample throughput. METHODS:
      Thirty-five samples (HbF concentration: between 1.4 and 90.1%) and 68 samples
      (HbF concentration: <1.0%) were analyzed by high performance liquid
      chromatography (Tosoh G8) and BM Test HbA1c. The results by BM Test HbA1c were
      compared with those by the high performance liquid chromatography and
      International Federation of Clinical Chemistry reference method. RESULTS: The
      high and positive correlation coefficient was demonstrated between the enzymatic
      and International Federation of Clinical Chemistry methods for the samples with
      normal HbF concentration. The samples with high HbF concentration exhibited high
      and positive correlation coefficient, although the figure is lower than that of
      the normal HbF concentration group. CONCLUSIONS: BM Test HbA1c revealed a high
      and positive correlation with high performance liquid chromatography and
      International Federation of Clinical Chemistry reference methods. However, the
      HbA1c values by BM Test HbA1c and high performance liquid chromatography method
      were lower than those by International Federation of Clinical Chemistry reference
      method when the HbF concentration was high. BM Test HbA1c had some deviation from
      the International Federation of Clinical Chemistry reference method, while no
      significant interference was seen when the HbF values were less than 15%. When
      HbF is higher than 15%, however, the interpretation of HbA1c by BM Test may
      require some special consideration.

PMID- 25587199
TI  - The Pot Calling the Kettle Black? A Comparison of Measures of Current Tobacco
      Use.
AB  - Researchers often use the discrepancy between self-reported and biochemically
      assessed active smoking status to argue that self-reported smoking status is not
      reliable, ignoring the limitations of biochemically assessed measures and
      treating it as the gold standard in their comparisons. Here, we employ
      econometric techniques to compare the accuracy of self-reported and biochemically
      assessed current tobacco use, taking into account measurement errors with both
      methods. Our approach allows estimating and comparing the sensitivity and
      specificity of each measure without directly observing true smoking status. The
      results, robust to several alternative specifications, suggest that there is no
      clear reason to think that one measure dominates the other in accuracy.

PMID- 25587200
TI  - Pseudo-empirical Likelihood-Based Method Using Calibration for Longitudinal Data
      with Drop-Out.
AB  - In observational studies, interest mainly lies in estimation of the population
      level relationship between the explanatory variables and dependent variables, and
      the estimation is often undertaken using a sample of longitudinal data. In some
      situations, the longitudinal data sample features biases and loss of estimation
      efficiency due to non-random drop-out. However, inclusion of population-level
      information can increase estimation efficiency. In this paper we propose an
      empirical likelihood-based method to incorporate population-level information in
      a longitudinal study with drop-out. The population-level information is
      incorporated via constraints on functions of the parameters, and non-random drop
      out bias is corrected by using a weighted generalized estimating equations
      method. We provide a three-step estimation procedure that makes computation
      easier. Some commonly used methods are compared in simulation studies, which
      demonstrate that our proposed method can correct the non-random drop-out bias and
      increase the estimation efficiency, especially for small sample size or when the
      missing proportion is high. In some situations, the efficiency improvement is
      substantial. Finally, we apply this method to an Alzheimer's disease study.

PMID- 25587201
TI  - Whole-body cortisol response of zebrafish to acute net handling stress.
AB  - Zebrafish, Danio rerio, are frequently handled during husbandry and experimental
      procedures in the laboratory, yet little is known about the physiological
      responses to such stressors. We measured the whole-body cortisol levels of adult
      zebrafish subjected to net stress and air exposure at intervals over a 24 h
      period; cortisol recovered to near control levels by about 1 h post-net-stress
      (PNS). We then measured cortisol at frequent intervals over a 1 h period.
      Cortisol levels were more than 2-fold higher in net stressed fish at 3 min PNS
      and continued to increase peaking at 15 min PNS, when cortisol levels were 6-fold
      greater than the control cortisol. Mean cortisol declined from 15 to 60 min PNS,
      and at 60 min, net-stressed cortisol was similar to control cortisol. Because the
      age of fish differed between studies, we examined resting cortisol levels of fish
      of different ages (3, 7, 13, and 19 months). The resting cortisol values among
      tanks with the same age fish differed significantly but there was no clear effect
      of age. Our study is the first to report the response and recovery of cortisol
      after net handling for laboratory-reared zebrafish.

PMID- 25587202
TI  - Trait Rumination Is Associated with Enhanced Recollection of Negative Words.
AB  - Rumination is associated with Major Depressive Disorder (MDD). To better
      understand this association, researchers have begun to investigate the
      relationship between rumination and cognitive biases that are linked to MDD. To
      date, several studies have found that rumination is related to negatively biased
      memory, but it is not clear whether this relationship is independent of
      depressive symptoms. To address this question, the present study examined 97
      healthy Caucasian women between the ages of 18 and 25. Participants performed an
      encoding task of self-referent adjectives, followed by a recognition task. The
      recognition task utilized a remember/know paradigm to separately examine
      recollection-based memory and familiarity-based memory. Trait rumination was
      assessed using the ruminative response scale (RRS). Results indicate that high
      trait rumination is associated with selective enhancement of recollection for
      negative words compared to neutral words and a trend toward selective enhancement
      for recollection for negative words compared to positive words. Trait rumination
      does not affect biases in overall recognition sensitivity or familiarity.

PMID- 25587203
TI  - A Methodology for Robust Multiproxy Paleoclimate Reconstructions and Modeling of
      Temperature Conditional Quantiles.
AB  - Great strides have been made in the field of reconstructing past temperatures
      based on models relating temperature to temperature-sensitive paleoclimate
      proxies. One of the goals of such reconstructions is to assess if current climate
      is anomalous in a millennial context. These regression based approaches model the
      conditional mean of the temperature distribution as a function of paleoclimate
      proxies (or vice versa). Some of the recent focus in the area has considered
      methods which help reduce the uncertainty inherent in such statistical
      paleoclimate reconstructions, with the ultimate goal of improving the confidence
      that can be attached to such endeavors. A second important scientific focus in
      the subject area is the area of forward models for proxies, the goal of which is
      to understand the way paleoclimate proxies are driven by temperature and other
      environmental variables. One of the primary contributions of this paper is novel
      statistical methodology for (1) quantile regression with autoregressive residual
      structure, (2) estimation of corresponding model parameters, (3) development of a
      rigorous framework for specifying uncertainty estimates of quantities of
      interest, yielding (4) statistical byproducts that address the two scientific
      foci discussed above. We show that by using the above statistical methodology we
      can demonstrably produce a more robust reconstruction than is possible by using
      conditional-mean-fitting methods. Our reconstruction shares some of the common
      features of past reconstructions, but we also gain useful insights. More
      importantly, we are able to demonstrate a significantly smaller uncertainty than
      that from previous regression methods. In addition, the quantile regression
      component allows us to model, in a more complete and flexible way than least
      squares, the conditional distribution of temperature given proxies. This
      relationship can be used to inform forward models relating how proxies are driven
      by temperature.

PMID- 25587204
TI  - Immigrants' children's transition to secondary school in Italy.
AB  - Choosing a secondary school represents an important step in the lives of students
      in Italy, in that it has a strong bearing on their ultimate educational
      achievement and labor force trajectory. In this paper, we analyze the effect of
      generational status and length of residence on the transition to secondary school
      among immigrants living in Italy. Using data from the ITAGEN2 follow-up, we
      analyze scholastic results from the middle school final exam and the choice of
      secondary school among the adolescents in Italy. Children of immigrants are more
      likely to have inferior outcomes on the middle school exam and to enroll in
      vocational and polytechnic schools. Our multivariate results indicate that, after
      controlling for the family's human capital and other key background factors,
      immigrant students show greater propensity to choose a vocational path.
      Differences between immigrants and natives in secondary school tracks are also
      manifest when previous scholastic results are taken into account.

PMID- 25587205
TI  - Association of polymorphisms of genes involved in lipid metabolism with blood
      pressure and lipid values in mexican hypertensive individuals.
AB  - Hypertension and dyslipidemia exhibit an important clinical relationship because
      an increase in blood lipids yields an increase in blood pressure (BP). We
      analyzed the associations of seven polymorphisms of genes involved in lipid
      metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC
      rs1800588, LPL rs328, and MTTP rs1800591) with blood pressure and lipid values in
      Mexican hypertensive (HT) patients. A total of 160 HT patients and 160
      normotensive individuals were included. Genotyping was performed through PCR
      RFLP, PCR-AIRS, and sequencing. The results showed significant associations in
      the HT group and HT subgroups classified as normolipemic and hyperlipemic. The
      alleles FABP2 p.55T, LIPC -514T, and MTTP -493T were associated with elevated
      systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T
      were associated with decreased total cholesterol and LDL-C, respectively; APOA5
      p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased
      triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides.
      The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17
      2.93; P = 0.001) under the dominant model. These findings indicate that
      polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and
      may be important in the development of essential hypertension and dyslipidemia in
      Mexican HT patients. 

PMID- 25587207
TI  - Mobile, Social, and Wearable Computing and the Evolution of Psychological
      Practice.
AB  - Psychological assessment and intervention are extending from the clinic into
      daily life. Multiple forces are at play: Advances in mobile technology,
      constrained clinical care, and consumer demand for contextualized,
      nonstigmatizing, and low-cost alternatives are beginning to change the face of
      psychological assessment and interventions. Mobile, social, and wearable
      technologies are now enabling individuals to measure themselves and to integrate
      myriad forms of help and entertainment. The massive data sets generated by self
      tracking of mood and passive sensing of voice, activity, and physiology may
      eventually reorganize taxonomies of mental health concerns. Compelling mobile
      therapies will also emerge, involving contextually appropriate, entertaining, and
      dynamic feedback to provide help in the context of daily life. The efficacy of
      such applications will be tested through citizen science as well as clinical
      trials. This article reviews technical advances that can be applied to enhance
      assessment and intervention and dramatically increase access to psychotherapy. It
      is recommended that, in addition to exploring clinically oriented products,
      practitioners should support patients' use of direct-to-consumer applications in
      ways that align with therapeutic objectives.

PMID- 25587206
TI  - Stepwise application of urine markers to detect tumor recurrence in patients
      undergoing surveillance for non-muscle-invasive bladder cancer.
AB  - BACKGROUND: The optimal use of urine markers in the surveillance of non-muscle
      invasive bladder cancer (NMIBC) remains unclear. Aim of the present study was to
      investigate the combined and stepwise use of the four most broadly available
      urine markers to detect tumor recurrence in patients undergoing surveillance of
      NMIBC. PATIENTS AND METHODS: 483 patients with history of NMIBC were included.
      Cytology, UroVysion, fluorescence in situ hybridization (FISH), immunocytology
      (uCyt+), and NMP22 ELISA were performed before surveillance cystoscopy.
      Characteristics of single tests and combinations were assessed by contingency
      analysis. RESULTS: 128 (26.5%) patients had evidence of tumor recurrence.
      Sensitivities and negative predictive values (NPVs) of the single tests ranged
      between 66.4-74.3 and 82.3-88.2%. Two-marker combinations showed sensitivities
      and NPVs of 80.5-89.8 and 89.5-91.2%. A stepwise application of the two-test
      combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+
      and FISH) showed NPVs for high-risk recurrences (G3/Cis/pT1) of 98.8, 98.8, and
      99.1%, respectively. CONCLUSIONS: Combinations of cytology, FISH, immunocytology,
      and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test
      combinations of cytology, FISH, and immunocytology have a low probability of
      missing a high-risk tumor. The high sensitivities may justify the use of these
      combinations in prospective studies assessing the use of urine markers to
      individualize intervals between cystoscopies during follow-up.

PMID- 25587208
TI  - Acute exercise-induced response of monocyte subtypes in chronic heart and renal
      failure.
AB  - PURPOSE: Monocytes (Mon1-2-3) play a substantial role in low-grade inflammation
      associated with high cardiovascular morbidity and mortality of patients with
      chronic kidney disease (CKD) and chronic heart failure (CHF). The effect of an
      acute exercise bout on monocyte subsets in the setting of systemic inflammation
      is currently unknown. This study aims (1) to evaluate baseline distribution of
      monocyte subsets in CHF and CKD versus healthy subjects (HS) and (2) to evaluate
      the effect of an acute exercise bout. Exercise-induced IL-6 and MCP-1 release are
      related to the Mon1-2-3 response. METHODS: Twenty CHF patients, 20 CKD patients,
      and 15 HS were included. Before and after a maximal cardiopulmonary exercise
      test, monocyte subsets were quantified by flow cytometry: CD14(++)CD16(-)CCR2(+)
      (Mon1), CD14(++)CD16(+)CCR2(+) (Mon2), and CD14(+)CD16(++)CCR2(-) (Mon3). Serum
      levels of IL-6 and MCP-1 were determined by ELISA. RESULTS: Baseline distribution
      of Mon1-2-3 was comparable between the 3 groups. Following acute exercise, %Mon2
      and %Mon3 increased significantly at the expense of a decrease in %Mon1 in HS and
      in CKD. This response was significantly attenuated in CHF (P < 0.05). In HS only,
      MCP-1 levels increased following exercise; IL-6 levels were unchanged.
      Circulatory power was a strong and independent predictor of the changes in Mon1
      (beta = -0.461, P < 0.001) and Mon3 (beta = 0.449, P < 0.001); and baseline LVEF
      of the change in Mon2 (beta = 0.441, P < 0.001). CONCLUSION: The response of
      monocytes to acute exercise is characterized by an increase in proangiogenic and
      proinflammatory Mon2 and Mon3 at the expense of phagocytic Mon1. This exercise
      induced monocyte subset response is mainly driven by hemodynamic changes and not
      by preexistent low-grade inflammation.

PMID- 25587209
TI  - Brain-derived neurotrophic factor in chronic periodontitis.
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor
      family. Outside the nervous system, BDNF has been shown to be expressed in
      various nonneural tissues, such as periodontal ligament, dental pulp, and
      odontoblasts. Although a role for BDNF in periodontal regeneration has been
      suggested, a function for BDNF in periodontal disease has not yet been studied.
      The aim of this study was to analyze the BDNF levels in periodontal tissues of
      patients with chronic periodontitis (CP) and periodontally healthy controls (HC).
      All subjects were genotyped for the rs4923463 and rs6265 BDNF polymorphisms.
      Periodontal tissues were collected for ELISA, myeloperoxidase (MPO), and
      microscopic analysis from 28 CP patients and 29 HC subjects. BDNF levels were
      increased in CP patients compared to HC subjects. A negative correlation was
      observed when analyzing concentration of BDNF and IL-10 in inflamed periodontium.
      No differences in frequencies of BDNF genotypes between CP and HC subjects were
      observed. However, BDNF genotype GG was associated with increased levels of BDNF,
      TNF-alpha, and CXCL10 in CP patients. In conclusion, BDNF seems to be associated
      with periodontal disease process, but the specific role of BDNF still needs to be
      clarified. 

PMID- 25587210
TI  - Outcomes of the use of fully covered esophageal self-expandable stent in the
      management of colorectal anastomotic strictures and leaks.
AB  - Introduction. Colorectal anastomotic leak or stricture is a dreaded complication
      leading to significant morbidity and mortality. The novel use of self-expandable
      metal stents (SEMS) in the management of postoperative colorectal anastomotic
      leaks or strictures can avoid surgical reintervention. Methods. Retrospective
      study with particular attention to the indications, operative or postoperative
      complications, and clinical outcomes of SEMS placement for patients with either a
      colorectal anastomotic stricture or leak. Results. Eight patients had SEMS
      (WallFlex stent) for the management of postoperative colorectal anastomotic leak
      or stricture. Five had a colorectal anastomotic stricture and 3 had a colorectal
      anastomotic leak. Complete resolution of the anastomotic stricture or leak was
      achieved in all patients. Three had recurrence of the anastomotic stricture on 3
      month flexible sigmoidoscopy follow-up after the initial stent was removed. Two
      of these patients had a stricture that was technically too difficult to place
      another stent. Stent migration was noted in 2 patients, one at day 3 and the
      other at day 14 after stent placement that required a larger 23 mm stent to be
      placed. Conclusions. The use of SEMS in the management of colorectal anastomotic
      leaks or strictures is feasible and is associated with high technical and
      clinical success rate. 

PMID- 25587211
TI  - Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile
      Refractive Index Correlation Function.
AB  - Optical interactions with biological tissue provide powerful tools for study,
      diagnosis, and treatment of disease. When optical methods are used in
      applications involving tissue, scattering of light is an important phenomenon. In
      imaging modalities, scattering provides contrast, but also limits imaging depth,
      so models help optimize an imaging technique. Scattering can also be used to
      collect information about the tissue itself providing diagnostic value. Therapies
      involving focused beams require scattering models to assess dose distribution. In
      all cases, models of light scattering in tissue are crucial to correctly
      interpreting the measured signal. Here, we review a versatile model of light
      scattering that uses the Whittle-Matern correlation family to describe the
      refractive index correlation function Bn (rd ). In weakly scattering media such
      as tissue, Bn (rd ) determines the shape of the power spectral density from which
      all other scattering characteristics are derived. This model encompasses many
      forms such as mass fractal and the Henyey-Greenstein function as special cases.
      We discuss normalization and calculation of optical properties including the
      scattering coefficient and anisotropy factor. Experimental methods using the
      model are also described to quantify tissue properties that depend on length
      scales of only a few tens of nanometers.

PMID- 25587212
TI  - Preperitoneal surgery using a self-adhesive mesh for inguinal hernia repair.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic preperitoneal hernia repair with mesh has
      been reported to result in improved patient outcomes. However, there are few
      published data on the use of a totally extraperitoneal (TEP) approach. The
      purpose of this study was to present our experience and evaluate early outcomes
      of TEP inguinal hernia repair with self-adhesive mesh. METHODS: This cohort study
      was a retrospective review of patients who underwent laparoscopic TEP inguinal
      hernial repair from April 4, 2010, through July 22, 2014. Data assessed were age,
      sex, body mass index (BMI), hernia repair indications, hernia type, pain,
      paresthesia, occurrence (bilateral or unilateral), recurrence, and patient
      satisfaction. Descriptive and regression analyses were performed. RESULTS: Six
      hundred forty patients underwent laparoscopic preperitoneal hernia surgery with
      self-adhesive mesh. The average age was 56 years, nearly all were men (95.8%),
      and the mean BMI was 26.2 kg/m(2). Cases involved primary hernia more frequently
      than recurrent hernia (94% vs 6%; P < .05). After surgery, 92% of the patients
      reported no more than minimal pain, <1% reported paresthesia, and 0.2% had early
      recurrence. There were 7 conversions to an open procedure. The patients had no
      adverse reactions to anesthesia and no bladder injury. Postoperative acute pain
      or recurrence was not explained by demographics, BMI, or preoperative pain. There
      were significant associations of hernia side, recurrence, occurrence, and sex
      with composite end points. Nearly all patients (98%) were satisfied with the
      outcome. CONCLUSION: The use of self-adhesive, Velcro-type mesh in laparoscopic
      TEP inguinal hernia repair is associated with reduced pain; low rates of early
      recurrence, infection, and hematoma; and improved patient satisfaction.

PMID- 25587213
TI  - Outcomes of conversion of laparoscopic colorectal surgery to open surgery.
AB  - OBJECTIVES: There is limited data regarding the outcomes of patients who undergo
      conversion to open surgery during a laparoscopic operation in colorectal
      resection. We sought to identify the outcomes of such patients. METHODS: The NIS
      (National Inpatient Sample) database was used to identify patients who had
      conversion from laparoscopic to open colorectal surgery during the 2009 to 2012
      period. Multivariate regression analysis was performed to identify risk-adjusted
      outcomes of conversion to open surgery. RESULTS: We sampled 776 007 patients who
      underwent colorectal resection. 337 732 (43.5%) of the patients had laparoscopic
      resection. Of these, 48 265 procedures (14.3%) were converted to open surgery.
      The mortality of converted patients was increased, when compared with
      successfully completed laparoscopic operations, but was still lower than that of
      open procedures (0.6% vs. 1.4% vs. 3.9%, respectively; adjusted odds ratio [AOR],
      1.61 and 0.58, respectively; P < .01). The most common laparoscopic colorectal
      procedure was right colectomy (41.2%). The lowest rate of conversion is seen with
      right colectomy while proctectomy had the highest rate of conversion (31.2% vs.
      12.9%, AOR, 2.81, P < .01). Postsurgical complications including intra-abdominal
      abscess (AOR, 2.64), prolonged ileus (AOR, 1.50), and wound infection (AOR, 2.38)
      were higher in procedures requiring conversion (P < .01). CONCLUSIONS: Conversion
      of laparoscopic to open colorectal resection occurs in 14.3% of cases. Compared
      with patients who had laparoscopic operations, patients who had conversion to
      open surgery had a higher mortality, higher overall morbidity, longer length of
      hospitalization, and increased hospital charges. The lowest conversion rate was
      in right colectomy and the highest was in proctectomy procedures. Wound infection
      in converted procedures is higher than in laparoscopic and open procedures.

PMID- 25587214
TI  - Laparoscopic techniques enable peritoneal dialysis in the difficult abdomen.
AB  - BACKGROUND AND OBJECTIVES: Continuous ambulatory peritoneal dialysis has become
      an increasingly popular modality of renal replacement therapy. Laparoscopic
      placement of peritoneal dialysis catheters may help overcome previous barriers to
      peritoneal dialysis, such as previous abdominal surgical procedures or the
      presence of hernias, without incurring substantially greater risks. METHODS: We
      performed a retrospective review of 120 consecutive patients who underwent
      attempted laparoscopic peritoneal dialysis catheter placement between July 2009
      and June 2014 by a single surgeon. Patient and catheter characteristics and
      outcomes were compared between patients with and without complications, as well
      as between patients with a history of major abdominal surgery and those without
      such a history. RESULTS: Laparoscopic peritoneal dialysis catheter placement was
      aborted in 4 patients because of an inability to safely achieve sufficient access
      to the abdominal cavity through dissection; these patients were excluded from
      subsequent analysis. The mean follow-up period was 18.8 +/- 12.9 months. Fifty
      five patients had a history of major abdominal surgery compared with 61 without
      such a history. No significant difference was observed with respect to age, race,
      sex, or body mass index between groups. Notably, more adjunctive procedures were
      required in patients with previous abdominal surgery, including adhesiolysis
      (60.0% vs 4.9%, P < .0001) and hernia repair (12.7% vs 1.6%, P = .026).
      Postoperative catheter complications were not significantly different between
      patients with and patients without a history of abdominal surgery (29.1% vs
      32.8%, P = .667). Both unassisted (56.8% vs 65.0%, P = .397) and overall (72.7%
      vs 76.7%, P = .647) 1-year catheter survival rates were similar between patients
      with and patients without previous surgery, and the overall 1-year survival rate
      improved to 83.9% on exclusion of patients who stopped peritoneal dialysis for
      nonsurgical reasons. CONCLUSIONS: Laparoscopic peritoneal dialysis catheter
      placement offers a chance to establish peritoneal dialysis access in patients
      traditionally viewed as noncandidates for this modality. Despite the potential
      risks incurred because of additional procedures at the time of catheter placement
      in these complicated cases, these patients can achieve good long-term peritoneal
      dialysis access with an aggressive surgical approach.

PMID- 25587215
TI  - Trends in splenectomy: where does laparoscopy stand?
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic splenectomy (LS) has been shown to offer
      superior outcomes when compared to open splenectomy (OS). Despite the potential
      advantages associated with the minimally invasive technique, laparoscopy appears
      to be underused. We sought to evaluate the nationwide trends in LS. METHODS: The
      Nationwide Inpatient Sample (NIS) database was queried for both OS and LS
      procedures performed from 2005 through 2010. Partial splenectomies and those
      performed for traumatic injury, vascular anomaly, or as part of a pancreatectomy
      were excluded. The included cases were examined for age of the patient and
      comorbid conditions. We then evaluated the postoperative complications, overall
      morbidity, mortality, and length of hospital stay. RESULTS: A total of 37,006
      splenectomies were identified. Of those, OS accounted for 30,108 (81.4%) cases,
      LS for 4,938 (13.3%), and conversion to open surgery (CS) for 1,960 (5.3%). The
      overall rate of morbidity was significantly less in the LS group than in the OS
      group (7.4% vs 10.4%; P < .0001). The LS group had less mortality (1.3% vs 2.5%,
      P < .05) and a shorter length of stay (5.6 +/- 8 days vs 7.5 +/- 9 days).
      CONCLUSIONS: Despite the benefits conferred by LS, it appears to be underused in
      the United States. There has been an improvement in the rate of splenectomies
      completed laparoscopically when compared to NIS data from the past (8.8% vs 13%;
      P < .05). The conversion rate is appreciably higher for LS than for other
      laparoscopic procedures, suggesting that splenectomies require advanced
      laparoscopic skills and that consideration should be given to referring patients
      in need of the procedure to appropriately experienced surgeons.

PMID- 25587217
TI  - Current clinical practice: differential management of uveal melanoma in the era
      of molecular tumor analyses.
AB  - OBJECTIVE: Assess current clinical practices for uveal melanoma (UM) and the
      impact of molecular prognostic testing on treatment decisions. DESIGN: Cross
      sectional survey and sequential medical records review. PARTICIPANTS:
      Ophthalmologists who treat UM. METHODS: (A) Medical records review of all
      Medicare beneficiaries tested by UM gene expression profile in 2012, conducted
      under an institutional review board-approved protocol. (B) 109 ophthalmologists
      specializing in the treatment of UM were invited to participate in 24-question
      survey in 2012; 72 were invited to participate in a 23-question survey in 2014.
      MAIN OUTCOME MEASURES: Responses analyzed by descriptive statistics, frequency
      analyses (percentages, Tukey, histograms), and Fisher's exact test. Descriptive
      presentation of essay answers. RESULTS: The review of Medicare medical records
      included 191 evaluable patients, 88 (46%) with documented medical treatment
      actions or institutional policies related to surveillance plans. Of these 88, all
      gene expression profiling (GEP) Class 1 UM patients were treated with low
      intensity surveillance. All GEP Class 2 UM patients were treated with high
      intensity surveillance (P<0.0001 versus Class 1). There were 36 (19%) with
      information concerning referrals after initial diagnosis. Of these 36, all 23
      Class 2 patients were referred to medical oncology; however, none of the 13 Class
      1 patients were referred (P<0.0001 versus Class 1). Only Class 2 patients were
      recommended for adjunctive treatment regimens. 2012 survey: 50 respondents with
      an annual median of 35 new UM patients. The majority of respondents (82%)
      performed molecular analysis of UM tumors after fine needle biopsy (FNAB);
      median: 15 FNAB per year; 2014 survey: 35 respondents with an annual median of 30
      new UM patients. The majority offered molecular analyses of UM tumor samples to
      most patients. Patients with low metastatic risk (disomy 3 or GEP Class 1) were
      generally assigned to less frequent (every 6 or 12 months) and less intensive
      clinical visits. Patients with high metastatic risk (monosomy 3 or GEP Class 2)
      were assigned to more frequent surveillance with hepatic imaging and liver
      function testing every 3-6 months. High-risk patients were considered more
      suitable for adjuvant treatment protocols. CONCLUSION: The majority of
      ophthalmologists treating UM have adopted molecular diagnostic tests for the
      purpose of designing risk-appropriate treatment strategies.

PMID- 25587216
TI  - Cationic liposome-nucleic acid complexes for gene delivery and gene silencing.
AB  - Cationic liposomes (CLs) are studied worldwide as carriers of DNA and short
      interfering RNA (siRNA) for gene delivery and gene silencing, and related
      clinical trials are ongoing. Optimization of transfection efficiency and
      silencing efficiency by cationic liposome carriers requires a comprehensive
      understanding of the structures of CL-nucleic acid complexes and the nature of
      their interactions with cell membranes as well as events leading to release of
      active nucleic acids within the cytoplasm. Synchrotron x-ray scattering has
      revealed that CL-nucleic acid complexes spontaneously assemble into distinct
      liquid crystalline phases including the lamellar, inverse hexagonal, hexagonal,
      and gyroid cubic phases, and fluorescence microscopy has revealed CL-DNA pathways
      and interactions with cells. The combining of custom synthesis with
      characterization techniques and gene expression and silencing assays has begun to
      unveil structure-function relations in vitro. As a recent example, this review
      will briefly describe experiments with surface-functionalized PEGylated CL-DNA
      nanoparticles. The functionalization, which is achieved through custom synthesis,
      is intended to address and overcome cell targeting and endosomal escape barriers
      to nucleic acid delivery faced by PEGylated nanoparticles designed for in vivo
      applications.

PMID- 25587218
TI  - A single blind randomized control trial on support groups for Chinese persons
      with mild dementia.
AB  - PURPOSE: Persons with mild dementia experience multiple losses and manifest
      depressive symptoms. This research study aimed to evaluate the effectiveness of a
      support group led by a social worker for Chinese persons with mild dementia.
      RESEARCH METHODS: Participants were randomly assigned to either a ten-session
      support group or a control group. Standardized assessment tools were used for
      data collection at pretreatment and post-treatment periods by a research
      assistant who was kept blind to the group assignment of the participants. Upon
      completion of the study, 20 treatment group participants and 16 control group
      participants completed all assessments. RESULTS: At baseline, the treatment and
      control groups did not show any significant difference on all demographic
      variables, as well as on all baseline measures; over one-half (59%) of all the
      participants reported having depression, as assessed by a Chinese Geriatric
      Depression Scale score >=8. After completing the support group, the depressive
      mood of the treatment group participants reduced from 8.83 (standard deviation
      =2.48) to 7.35 (standard deviation =2.18), which was significant (Wilcoxon signed
      rank test; P=0.017, P<0.05), while the control group's participants did not show
      any significant change. CONCLUSION: This present study supports the efficacy and
      effectiveness of the support group for persons with mild dementia in Chinese
      society. In particular, this present study shows that a support group can reduce
      depressive symptoms for participants.

PMID- 25587220
TI  - Induction of multiple drug resistance in HMEC-1 endothelial cells after long-term
      exposure to sunitinib.
AB  - Multiple drug resistance is still an unsolved problem in cancer therapy. Our
      previous study demonstrated that the chemotherapeutic drug doxorubicin (Dox)
      induced upregulation of P-glycoprotein (P-gp) in endothelial cells, resulting in
      a 20-fold increase in drug resistance and reduced efficiency of Dox treatment in
      a mice tumor model. In this study, we exposed human microvascular endothelial
      cells (HMEC-1) to sunitinib, a tyrosine kinase receptor inhibitor, to induce drug
      resistance. The results show that sunitinib treatment induced multiple drug
      resistance in these cells. They became resistant not only to sunitinib but also
      to Dox, paclitaxel, and vinblastine. Significant increases in P-gp (9.3-fold),
      ABCG2 (breast cancer resistance protein, 1.9-fold), and multidrug resistance
      associated protein 1 (2.7-fold) gene transcription were found by quantitative
      polymerase chain reaction quantification, and their protein expression was
      confirmed by Western blot. These increases gave rise to an approximately five
      fold increase in half maximal inhibitory concentration in these cells in response
      to sunitinib treatment in vitro. The inhibitors of adenosine triphosphate-binding
      cassette transporters did not reverse the drug resistance in sunitinib-resistant
      HMEC-1 cells, assumedly because of a blockage of the pump function caused by
      sunitinib. Our study indicates that the antiangiogenic drug sunitinib induces
      multiple drug resistance in endothelial cells. The induction of adenosine
      triphosphate-binding cassette transporters seems not to be responsible for
      observed multiple drug resistance, and the underlying mechanisms remain unknown. 

PMID- 25587222
TI  - Dr Noni E MacDonald Award.

PMID- 25587219
TI  - Prevalence and correlates of suicide ideation in patients with COPD: a mixed
      methods study.
AB  - PURPOSE: The purpose of this study was to examine the prevalence and correlates
      of suicidal ideation (SI) in patients with stable moderate to very severe chronic
      obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We conducted an
      exploratory mixed methods analysis of data from participants in a longitudinal
      observational study of depression in COPD. We measured depression with the
      Patient Health Questionnaire-9 (PHQ-9), which includes an item on SI. We compared
      participants with and without SI in relation to sociodemographics, symptoms,
      anxiety, and healthcare resource use with independent t-tests and chi-square
      tests. Content analysis was performed on qualitative data gathered during a
      structured SI safety assessment. RESULTS: Of 202 participants, 121 (60%) had
      depressive symptoms (PHQ >=6); 51 (25%) had a PHQ-9 >=10, indicating a high
      likelihood of current major depression; and 22 (11%) reported SI. Compared to the
      99 depressed participants without SI, those with SI were more likely to be female
      (59% vs 27%, P=0.004); had worse dyspnea (P=0.009), depression (P<0.001), and
      anxiety (P=0.003); and were also more likely to have received treatment for
      depression and/or anxiety (82% vs 40%, P<0.001) and more hospitalizations for
      COPD exacerbations (P=0.03) but had similar levels of airflow obstruction and
      functioning than participants without SI. Themes from the qualitative analysis
      among those with SI included current or prior adverse life situations, untreated
      or partially treated complex depression, loss of a key relationship, experience
      of illness and disability, and poor communication with providers. CONCLUSION: Our
      findings suggest that current SI is common in COPD, may occur disproportionately
      in women, can persist despite mental health treatment, and has complex
      relationships with both health and life events. Adequate management of SI in COPD
      may therefore require tailored, comprehensive treatment approaches that integrate
      medical and mental health objectives.

PMID- 25587223
TI  - Ponseti clubfoot management: Experience with the Steenbeek foot abduction brace.

PMID- 25587225
TI  - Case 1: Hyperpigmented swirly patches in a toddler.

PMID- 25587224
TI  - A novel MC4R mutation associated with childhood-onset obesity: A case report.
AB  - The melanocortin-4-receptor gene (MC4R) is a key regulator of energy homeostasis,
      food intake and body weight. MC4R gene mutations are associated with early-onset
      severe obesity. Most patients are heterozygotes, with some reports of homozygotes
      and compound heterozygotes. The authors report a case involving an eight-year-old
      girl with progressive weight gain from infancy, body mass index 44 kg/m(2) (>97th
      percentile), hyperphagia, hyperinsulinemia and increased linear growth. There was
      no phenotype of morbid obesity in the parents or sibling. Coding regions and
      intron-exon boundaries of the genes encoding leptin, leptin receptor, pro
      opiomelanocortin and MC4R were analyzed. Two heterozygous coding mutations in the
      MCR4 gene (S94N and C293R) were detected, of which the second has not been
      previously reported. The mutations were on opposite chromosomes, confirming
      compound heterozygosity. The molecular findings and clinical features associated
      with this novel MC4R mutation are described. The authors emphasize that rare
      mutations can be found in some patients with severe childhood-onset obesity. 

PMID- 25587221
TI  - Long-term efficacy and safety of human papillomavirus vaccination.
AB  - In this paper, we review the published evidence about the long-term efficacy of
      the available human papillomavirus (HPV) vaccines and their safety profile. Two
      prophylactic HPV vaccines - bivalent (bHPV) and quadrivalent (qHPV) - are now
      available, and vaccination programs are being widely implemented, primarily
      targeting adolescent girls. Efficacy has been widely demonstrated for both
      vaccines. Since the risk of HPV exposure potentially persists throughout a
      woman's sexual life, vaccine duration of protection is critical to overall
      effectiveness. Interpreting the results of long-term efficacy studies for the two
      HPV vaccines can be puzzling, due to the heterogeneity of studies, different
      methods used in the assessment of immunogenicity, histopathological and
      virological end points, and statistical power issues. Moreover, an immunologic
      correlate of protection has not yet been established, and it is unknown whether
      higher antibody levels will really result in a longer duration of protection.
      Disease prevention remains the most important measure of long-term duration of
      vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4
      years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8
      years. The vaccine continues to be immunogenic and well tolerated up to 9 years
      following vaccination. All randomized controlled clinical trials of the bHPV and
      the qHPV vaccines provide evidence of an excellent safety profile. The most
      common complaint reported is pain in the injection site, which is self-limiting
      and spontaneously resolved. The incidence of systemic adverse events (AEs),
      serious AEs, and discontinuations due to a serious AE reported in clinical
      studies are similar between the two vaccines and their control groups. In
      particular, no increased risk of autoimmune disease has been shown among HPV
      vaccinated subjects in long-term observation studies. As these are crucial topics
      in HPV vaccination, it is important to establish systems for continued monitoring
      of vaccine immunogenicity, efficacy, and safety over time. 

PMID- 25587226
TI  - Case 2: An 11-year-old girl with aggressive behaviour and intellectual
      impairment.

PMID- 25587227
TI  - Case 3: Stridor and cough in a young child.

PMID- 25587228
TI  - Case 4: Recurrent bacterial meningitis in an adolescent female.

PMID- 25587229
TI  - Cyberbullying: Hiding behind the screen.

PMID- 25587230
TI  - Lactose avoidance for young children with acute diarrhea.

PMID- 25587231
TI  - Combined and alternating acetaminophen and ibuprofen therapy for febrile
      children.

PMID- 25587232
TI  - Children who 'grow up' in hospital: Inpatient stays of six months or longer.
AB  - OBJECTIVE: To describe the clinical course of all infants and children
      hospitalized for six consecutive months (180 days) or longer at a
      tertiary/quaternary children's hospital in Western Canada. METHODS: A
      retrospective review of medical records for all eligible patients from January 1,
      2007 to December 31, 2012 at Stollery Children's Hospital (Edmonton, Alberta) was
      performed. RESULTS: A total of 61 patients experienced 64 eligible
      hospitalizations. The mean length of stay was 326 days, corresponding to a
      cumulative 20,892 hospital days (57.2 patient-years). Prevalent procedures
      resulting in long hospitalization were long-term tracheostomy +/- ventilation in
      32 (52%) patients, need for organ transplantation in 24 (39%) with completed
      transplantation in 15 (25%), and ventricular-assist devices (VADs) in seven
      (11%). Sixteen (26%) patients in the study group died, and 16 (26%) were placed
      in long-term care or out-of-home care at the end of their long hospitalization.
      Of children displaced from their family home, 14 (88%) were Aboriginal.
      CONCLUSION: Infants and children who experience very long hospitalizations have
      complex illnesses, with substantial risk for mortality and a high rate of
      displacement from their families after discharge. Aboriginal children appear to
      be particularly vulnerable to displacement and problem solving for this
      population must be undertaken, involving a variety of stakeholders.

PMID- 25587233
TI  - Paediatric patient family engagement with clinical research at a tertiary care
      paediatric hospital.
AB  - BACKGROUND: Subject recruitment is essential for conducting clinical research;
      however, there are very few studies evaluating research uptake by families in a
      paediatric setting. OBJECTIVES: To determine how frequently paediatric patients
      and their families receiving care at a tertiary paediatric hospital participated
      in research. The secondary objectives were to explore factors that influence
      patient families' decisions to participate in research and how they perceived
      their experiences. METHODS: A cross-sectional study surveying families of
      children receiving care in a sample of clinical areas at a tertiary care
      paediatric hospital in British Columbia was conducted. A self-administered
      questionnaire was used, and was facilitated by trained interviewers. Descriptive
      statistics were used to report the proportion of patient families that have
      previously been invited to participate in research and, among these, the
      proportion who had agreed to participate. Patient families' perceptions of
      research and their past experiences therein were also reported. RESULTS: A total
      of 657 families were approached, of which 543 were enrolled (82.6% response
      rate). Among the 439 families that had visited the hospital previously, 114
      (26.0%) had been invited to participate in research and 99 (87%) had consented to
      participate. Of these 99 families, only one had a negative experience, and 84
      (85%) of these participant families were at least somewhat likely to participate
      in research again in the future. CONCLUSIONS: Only one-quarter of families that
      had previously visited the hospital had been invited to participate in a research
      project. Of the families approached previously, there was a high rate of
      participation and willingness to participate in future research.

PMID- 25587234
TI  - A population-based study of paediatric emergency department and office visits for
      concussions from 2003 to 2010.
AB  - BACKGROUND: There is a paucity of information regarding descriptive epidemiology
      of paediatric concussions over time, and few studies include both emergency
      department (ED) and physician office visits. OBJECTIVE: To describe trends in
      visits for paediatric concussions in both EDs and physician offices according to
      age and sex. A secondary objective was to describe the cause of concussion for
      children treated in EDs. METHODS: A retrospective, population-based study using
      linked health administrative data from all concussion-related visits to the ED or
      a physician office by school-age children and youth (three to 18 years of age) in
      Ontario between April 1, 2003 and March 3, 2011 was conducted. RESULTS: The
      number of children evaluated in both EDs and a physician offices increased
      between 2003 and 2010, and this linear trend was statistically significant
      (P=0.002 for ED visits and P=0.001 for office visits). The rate per 100,000
      increased from 466.7 to 754.3 for boys and from 208.6 to 440.7 for girls during
      the study period. Falls accounted for approximately one-third of the paediatric
      concussions. Hockey/skating was the most common specific cause of paediatric
      sports-related concussions. CONCLUSIONS: The increasing use of health care
      services for concussions is likely related to changes in incidence over time and
      increased awareness of concussion as a health issue. Evidence-based prevention
      initiatives to help reduce the incidence of concussion are warranted,
      particularly in sports and recreation programs.

PMID- 25587235
TI  - Nutrition for healthy term infants, six to 24 months: An overview.
AB  - Nutrition for Healthy Term Infants is a joint statement by Health Canada, the
      Canadian Paediatric Society, Dietitians of Canada and the Breastfeeding Committee
      for Canada. It was republished in September 2012, with recommendations on infant
      feeding from birth to six months of age. The statement was most recently updated
      in April 2014, with recommendations for feeding older infants and young children
      from six to 24 months of age. The present practice point outlines the statement
      development process and principles of feeding, with specific recommendations for
      clinicians. Health professionals who counsel families on nutrition in infants and
      young children are advised to read the statement in its entirety because
      discussion in the longer document expands on and clarifies advice summarized in
      the principles and recommendations given here. The complete statement is
      available on Health Canada's website: www.hc-sc.gc.ca/fn-an/nutrition/infant
      nourisson/index-eng.php. 

PMID- 25587236
TI  - Increasing the use of influenza vaccines in children with egg allergy.
AB  - Administration of inactivated trivalent or quadrivalent influenza vaccines is now
      believed to be safe for individuals with egg allergy. Unless children have
      experienced an anaphylactic reaction to a previous dose of influenza vaccine,
      they can and should be immunized with a full dose of trivalent or quadrivalent
      inactivated vaccine. 

PMID- 25587237
TI  - The benefits of influenza vaccine in pregnancy for the fetus and the infant
      younger than six months of age.
AB  - Influenza is a serious problem for infants <6 months of age, whose
      hospitalization rates for influenza and associated illness are comparable with
      rates in the elderly. Because influenza vaccines are not effective in this age
      group, the optimal evidence-based strategy is to administer trivalent inactivated
      influenza vaccines during pregnancy. Immunizing with trivalent inactivated
      influenza vaccines in the second and third trimester is well studied and safe,
      not only providing protection for the pregnant woman and her infant <6 months of
      age, but also for the fetus by decreasing the risk for low birth weight. 

PMID- 25587238
TI  - Evaluation of delivery of enteral nutrition in mechanically ventilated Malaysian
      ICU patients.
AB  - BACKGROUND: There are numerous challenges in providing nutrition to the
      mechanically ventilated critically ill ICU patient. Understanding the level of
      nutritional support and the barriers to enteral feeding interruption in
      mechanically ventilated patients are important to maximise the nutritional
      benefits to the critically ill patients. Thus, this study aims to evaluate
      enteral nutrition delivery and identify the reasons for interruptions in
      mechanically ventilated Malaysian patients receiving enteral feeding. METHODS: A
      cross sectional prospective study of 77 consecutive patients who required
      mechanical ventilation and were receiving enteral nutrition was done in an open
      14-bed intensive care unit of a tertiary hospital. Data were collected
      prospectively over a 3 month period. Descriptive statistical analysis were made
      with respect to demographical data, time taken to initiate feeds, type of feeds,
      quantification of feeds attainment, and reasons for feed interruptions. There are
      no set feeding protocols in the ICU. The usual initial rate of enteral nutrition
      observed in ICU was 20 ml/hour, assessed every 6 hours and the decision was made
      thereafter to increase feeds. The target calorie for each patient was determined
      by the clinician alongside the dietitian. The use of prokinetic agents was also
      prescribed at the discretion of the attending clinician and is commonly IV
      metoclopramide 10 mg three times a day. RESULTS: About 66% of patients achieved
      80% of caloric requirements within 3 days of which 46.8% achieved full feeds in
      less than 12 hours. The time to initiate feeds for patients admitted into the ICU
      ranged from 0 - 110 hours with a median time to start feeds of 15 hours and the
      interquartile range (IQR) of 6-59 hours. The mean time to achieve at least 80% of
      nutritional target was 1.8 days +/- 1.5 days. About 79% of patients experienced
      multiple feeding interruptions. The most prevalent reason for interruption was
      for procedures (45.1%) followed by high gastric residual volume (38.0%),
      diarrhoea (8.4%), difficulty in nasogastric tube placement (5.6%) and vomiting
      (2.9%). CONCLUSION: Nutritional inadequacy in mechanically ventilated Malaysian
      patients receiving enteral nutrition was not as common as expected. However,
      there is still room for improvement with regards to decreasing the number of
      patients who did not achieve their caloric requirement throughout their stay in
      the ICU.

PMID- 25587239
TI  - Music therapy to promote psychological and physiological relaxation in palliative
      care patients: protocol of a randomized controlled trial.
AB  - BACKGROUND: Music therapy is one of the most frequently used complementary
      therapies in different palliative care settings. Despite its long tradition and
      high acceptance by other health-care professionals, evidence on the effectiveness
      of music therapy interventions for terminally ill patients is rare. Recent
      reviews and health-care reports consistently point out the need of music
      therapists to provide an evidence-based rationale for their clinical treatments
      in this field. Therefore, the present study evaluates the psychological and
      physiological response of palliative care patients to a standardized music
      therapy relaxation intervention in a randomized controlled trial. METHODS/DESIGN:
      A sample of 84 participants from a palliative care unit in Heidelberg is
      randomized to either two sessions of music therapy or two sessions of a verbal
      relaxation exercise, each lasting 30 minutes. The music therapy sessions consist
      of live played monochord music and a vocal improvisation, the control group uses
      a prerecorded excerpt from the mindfulness-based stress reduction program
      containing no musical elements. Outcome measures include self-report data on
      subjective relaxation, well-being, pain intensity, and quality of life, as well
      as continuous recording of heart rate variability and blood volume pulse as
      indicators of autonomous nervous system functioning. DISCUSSION: To our
      knowledge, this study is the first clinical trial in Europe and one of very few
      randomized controlled trials worldwide to systematically examine the effects of
      music therapy in palliative care. TRIAL REGISTRATION: German Clinical Trials
      Register - DRKS00006137.

PMID- 25587241
TI  - PRIORITIZATION OF PEDIATRIC CBRNE DISASTER PREPAREDNESS EDUCATION AND TRAINING
      NEEDS.
AB  - Children are the members of our population who are most vulnerable to the effects
      of a chemical, biological, radiological, nuclear or explosive (CBRNE) attack. It
      has been over 12 years since 9/11 and the majority of clinicians who would be
      providing care to children in the event of another attack still lack the
      requisite disaster preparedness training. The purpose of this report is to
      provide an overview of the recent developments that will enable the affordable
      creation of key CBRNE educational and just in time material. In 2011, the
      National Center for Disaster Medicine and Public Health (NCDMPH) convened a
      pediatric disaster preparedness conference. Much of the initial groundwork for
      development of a pediatric disaster preparedness curriculum, including the
      identification of target audiences and requisite role specific CBRNE curriculum
      content, was the product of this conference. Much of the needed pediatric
      education and training content for the diagnosis and treatment of the injurious
      effects of CBRNE has recently been both developed and well vetted. Bringing
      together these efforts in an educational program will result in a workforce that
      is better trained and prepared to address the needs of children impacted by these
      types of disasters.

PMID- 25587240
TI  - Unbearable suffering and requests for euthanasia prospectively studied in end-of
      life cancer patients in primary care.
AB  - BACKGROUND: An international discussion about whether or not to legally permit
      euthanasia and (or) physician assisted suicide (EAS) is ongoing. Unbearable
      suffering in patients may result in a request for EAS. In the Netherlands EAS is
      legally permitted, and unbearable suffering is one of the central compulsory
      criteria. The majority of EAS is performed in cancer patients in the primary care
      practice. In around one in every seven end-of-life cancer patients dying in the
      primary care setting EAS is performed. The prevalence of unbearable symptoms and
      overall unbearable suffering in relationship to explicit requests for EAS was
      studied in a cohort of end-of-life cancer patients in primary care. METHODS: A
      prospective study in primary care cancer patients estimated to die within six
      months was performed. Every two months suffering was assessed with the State-of
      Suffering V (SOS-V). The SOS-V is a comprehensive instrument for quantitative and
      qualitative assessment of unbearable suffering related to 69 physical,
      psychological and social symptoms in five domains. RESULTS: Out of 148 patients
      who were asked to participate 76 (51%) entered the study. The studied population
      were 64 patients who were followed up until death; 27% explicitly requested EAS,
      which was performed in 8% of the patients. The final interview per patient was
      analyzed; in four patients the SOS-V was missing. Unbearable symptoms were
      present in 94% of patients with an explicit request for EAS and in 87% of
      patients without an explicit request. No differences were found in the prevalence
      of unbearable suffering for physical, psychological, social and existential
      symptoms, nor for overall unbearable suffering, between patients who did or who
      did not explicitly request EAS. CONCLUSIONS: In a population of end-of-life
      cancer patients cared for in primary care no differences in unbearable suffering
      were found between patients with and without explicit requests for EAS. The study
      raises the question whether unbearable suffering is the dominant motive to
      request for EAS. Most patients suffered from unbearable symptoms, indicating that
      the compulsory criterion of unbearable suffering may be met a priori in most end
      of-life cancer patients dying at home, whether they request EAS or not.

PMID- 25587242
TI  - Trauma-Induced Coagulopathy.
AB  - Trauma is the leading cause of death among people under the age of 44. Hemorrhage
      is a major contributor to deaths related to trauma in the first 48 h.
      Accordingly, the management of these patients is a time-sensitive and critical
      affair that anesthesiologists responsible for surgical resuscitation will face.
      Coagulopathy associated with trauma exists in one-third of all severely injured
      patients upon presentation to the hospital. Trauma patients presenting with
      coagulopathy have significantly higher mortality. This trauma-induced
      coagulopathy (TIC) must be managed adroitly in the resuscitation of these
      patients. Recent advancements in our understanding of TIC have led to new
      protocols and therapy guidelines. Anesthesiologists must be aware of these to
      effectively manage this form of shock. TIC driven by a combination of endogenous
      biological processes, as well as iatrogenic causes, can ultimately lead to the
      lethal triad of hypothermia, acidemia, and coagulopathy. Providers should
      understand how to promptly diagnose TIC and be aware of the early indicators of
      massive transfusion. The use of common laboratory studies and patient vital signs
      serve as our current guide, but the importance of each is still under debate.
      Thromboelastography is a tool used often in the diagnosis of TIC and can be used
      to guide blood product transfusion. Certain pharmaceutical strategies and non
      transfusion strategies also exist, which aid in the management of hemorrhagic
      shock. Damage control surgery, rewarming, tranexamic acid, and 1:1:1 transfusion
      protocols are promising methods used to treat the critically wounded. Though
      protocols have been developed, controversies still exist on the optimal
      resuscitation strategy.

PMID- 25587244
TI  - CHRONIC NEONATAL DIAZOXIDE THERAPY IS NOT ASSOCIATED WITH ADVERSE EFFECTS.
AB  - Diazoxide is an ATP-sensitive potassium channel (KATP) agonist that has been
      shown to neuroprotective effects. These observations raise the possibility that
      diazoxide may have potential as a therapeutic agent for other applications. This
      study investigated (1) the long term effects of chronic neonatal administration
      of diazoxide and (2) the role of KATP on murin behavior and neurohistology.
      C57B/6J pups were injected daily with diazoxide (10, 20 or 50 mg kg-1) or vehicle
      from Postnatal days 2 (P2) through P12. Pups were allow to mature and underwent
      behavioral testing at 5-7 months of age. After behavioral testing, animals were
      euthanized and morphology of the brains was assessed. No long term adverse
      effects of neonatal diazoxide therapy on physical characteristics, visual acuity,
      sensori-motor reflexes, spontaneous locomotor activity, motor
      coordination/balance or motor learning and memory were observed. In addition, no
      morphological changes were observed on brains. However, we did observe that
      diazoxide therapy causes depressive-like phenotypes in female murine mice.
      Chronic neonatal diazoxide therapy does not cause deficits or enhancements in
      mice behavior. Diazoxide does not cause abnormal morphological changes in brain
      anatomy. However, diazoxide does cause gender specific depressive-like phenotype
      in mice.

PMID- 25587243
TI  - Mucocutaneous manifestations in juvenile-onset systemic lupus erythematosus: a
      review of literature.
AB  - Patients diagnosed with juvenile-onset systemic lupus erythematosus (JSLE) often
      have skin and oral lesions as part of their presentation. These mucocutaneous
      lesions, as defined by the American College of Rheumatology (ACR) in 1997,
      include malar rash, discoid rash, photosensitivity and oral ulcers. It is
      therefore essential to recognize mucocutaneous lesions to accurately diagnose
      JSLE. The mucocutaneous lesions can be divided into those with classical
      histological features (LE specific) and those strongly associated with and
      forming part of the diagnostic spectrum, but without the classical histological
      changes of lupus (LE nonspecific). A malar rash is the most commonly associated
      LE specific dermatological presentation. This skin manifestation is an acute form
      and also correlates with disease activity. Subacute (polycyclic or papulosquamous
      lesions) and chronic (discoid lesions) forms, whilst showing classical
      histological changes supportive of lupus, are less commonly associated with
      systemic lupus and do not correlate with disease activity. The most commonly
      associated skin lesions without classical lupus changes are cutaneous vasculitis,
      oral ulcers and diffuse non-scarring alopecia. These signs frequently relate to
      disease activity. An understanding of cutaneous signs and symptoms of lupus in
      children is important to avoid delay in diagnosis. They will often improve as
      lupus is adequately controlled and their reappearance is often the first
      indicator of a disease flare. 

PMID- 25587245
TI  - Voluntary peer review as innovative tool for quality improvement in the intensive
      care unit--a retrospective descriptive cohort study in German intensive care
      units.
AB  - INTRODUCTION: Quality improvement and safety in intensive care are rapidly
      evolving topics. However, there is no gold standard for assessing quality
      improvement in intensive care medicine yet. In 2007 a pilot project in German
      intensive care units (ICUs) started using voluntary peer reviews as an innovative
      tool for quality assessment and improvement. We describe the method of voluntary
      peer review and assessed its feasibility by evaluating anonymized peer review
      reports and analysed the thematic clusters highlighted in these reports. METHODS:
      Retrospective data analysis from 22 anonymous reports of peer reviews. All ICUs -
      representing over 300 patient beds - had undergone voluntary peer review. Data
      were retrieved from reports of peers of the review teams and representatives of
      visited ICUs. Data were analysed with regard to number of topics addressed and
      results of assessment questionnaires. Reports of strengths, weaknesses,
      opportunities and threats (SWOT reports) of these ICUs are presented. RESULTS:
      External assessment of structure, process and outcome indicators revealed high
      percentages of adherence to predefined quality goals. In the SWOT reports 11 main
      thematic clusters were identified representative for common ICUs. 58.1% of
      mentioned topics covered personnel issues, team and communication issues as well
      as organisation and treatment standards. The most mentioned weaknesses were
      observed in the issues documentation/reporting, hygiene and ethics. We identified
      several unique patterns regarding quality in the ICU of which long-term personnel
      problems und lack of good reporting methods were most interesting Conclusion:
      Voluntary peer review could be established as a feasible and valuable tool for
      quality improvement. Peer reports addressed common areas of interest in intensive
      care medicine in more detail compared to other methods like measurement of
      quality indicators.

PMID- 25587246
TI  - Soy and phytoestrogens: possible side effects.
AB  - Phytoestrogens are present in certain edible plants being most abundant in soy;
      they are structurally and functionally analogous to the estrogens. Phytoestrogens
      have been applied for compensation of hormone deficiency in the menopause. At the
      same time, soy products are used in infant food and other foodstuffs.
      Furthermore, soy is applied as animal fodder, so that residual phytoestrogens and
      their active metabolites such as equol can remain in meat and influence the
      hormonal balance of the consumers. There have been only singular reports on
      modified gender-related behavior or feminization in humans in consequence of soy
      consumption. In animals, the intake of phytoestrogens was reported to impact
      fertility, sexual development and behavior. Feminizing effects in humans can be
      subtle and identifiable only statistically in large populations. 

PMID- 25587247
TI  - GMS German Medical Science: Best paper award 2013.

PMID- 25587248
TI  - Seroepidemiological analysis of toxoplasmosis in college students.
AB  - BACKGROUND: Toxoplasmosis is a zoonosis caused by an obligate intracellular
      parasite, Toxoplasma gondii, which affects warm-blooded animals including humans.
      Its prevalence rates usually vary in different regions of the planet. METHODS: In
      this study, an analysis of the seroprevalence of toxoplasmosis among Brazilian
      students was proposed by means of IgG specific antibodies detection. The presence
      of anti-Toxoplasma gondii antibodies by indirect fluorescent antibody test (IFAT)
      was also evaluated in order to compare it with enzyme-linked immunosorbent assay
      (ELISA) and to assess the use of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic
      acid) and o-phenylenediamine dihydrochloride chromogens. RESULTS: The IFAT method
      showed a seroprevalence of 22.3%. These results were similar to those obtained by
      ELISA (24.1%). The seroprevalence was directly estimated from the IgG avidity,
      which showed that in a sample of 112 students, three of them had acute infection,
      an incidence of 1.6% in the studied population. CONCLUSION: In this study, the
      use of different chromogenic substrates in immunoenzymatic ELISA assays did not
      display different sensitivity in the detection of T. gondii-reagent serum. The
      extrapolation of results to this population must be carefully considered, since
      the investigation was conducted on a reduced sample. However, it allows us to
      emphasize the importance of careful and well prepared studies to identify risk
      factors for toxoplasmosis, to adopt preventive measures and to offer guidance to
      at-risk populations about the disease.

PMID- 25587249
TI  - Antioxidants and infertility treatment, the role of Satureja Khuzestanica: A mini
      systematic review.
AB  - BACKGROUND: The use of antioxidants in the treatment of infertility has been
      suggested and recent studies have indicated that oral administration of Satureja
      Khuzestanica essential oil (SKEO) to rats induces significant antioxidative
      effects. OBJECTIVE: This systematic review was conducted to evaluate the
      effectiveness of antioxidants in infertility and also to assess the effectiveness
      of Satureja Khuzestanica in infertility management. MATERIALS AND METHODS:
      Pubmed, Scopus, and Cochrane Library were searched for relevant trials published
      from respective database inception dates to August 2010. Study selection, and
      data extraction were performed by authors. RESULTS: Fifteen trials on evaluation
      of antioxidants in infertility and seven studies on the effectiveness of Satureja
      Khuzestanica were identified. Only 4 of the 15 trials were with application of
      allocation concealment and three studies were done in in-vitro environment.
      Despite the methodological and clinical heterogeneity of the trials, 14 of the 15
      (93.33%) trials showed an improvement in either sperm quality or pregnancy rate
      after antioxidant therapy. The human and animal studies of Satureja Khuzestanica
      showed a significant antioxidative potential of the plant and its effectiveness
      for infertility improvement. CONCLUSION: The use of oral antioxidants in
      infertility could improve sperm quality and pregnancy rates. Improved fertility
      observed by SKEO in rats might be due to its antioxidative effect. Further
      studies and clinical trials in humans are necessary to evaluate SKEO
      effectiveness in fertility disturbances.

PMID- 25587250
TI  - The effect of morphine consumption on plasma corticosteron concentration and
      placenta development in pregnant rats.
AB  - BACKGROUND: Previous studies have shown that morphine consumption during
      pregnancy may delay embryo development or cause abnormal nervous system function.
      OBJECTIVE: The present study focused on the effect of maternal morphine
      consumption on development of placenta and blood corticosteron concentration in
      addictive pregnant mothers. MATERIALS AND METHODS: 24 female rats, 170-200g
      weight, were used. The experimental groups after pregnancy received an oral dose
      of 0.05 mg/ml of morphine by tap water while the control group received only tap
      water. On 10(th) and 14(th) day of pregnancy, rats were anesthetized and placenta
      removed surgically, 1ml blood was collected from each pregnant mother from retro
      orbital sinus, the concentration of blood corticosteron was determined by
      corticosteron Elisa kit after centrifugation. The fixed tissue was processed,
      sectioned and stained with hematoxylin and eosin. Placenta was studied
      microscopically according to the thickness of layers, area of blood cisterns, and
      the number of cells. RESULTS: Comparing the plasma corticosteron concentration of
      the treatment and the control groups, not only a severe increase in the treatment
      group was detected, but also the thickness of maternal and embryonic portions of
      the placenta at day 10(th) and 14(th) of gestation was different significantly
      (p<=0.05). Furthermore, an increase in number of cells in maternal and embryonic
      portion of placenta and a decrease in blood cistern area were demonstrated in
      both the experimental and the control groups. CONCLUSION: The effects of
      morphine, including an increase in blood concentration of corticosteron, in
      dependent pregnant mothers were seen. Development of placenta in the experimental
      group was delayed.

PMID- 25587251
TI  - Observing principles of medical ethics during family planning services at Tehran
      urban healthcare centers in 2007.
AB  - BACKGROUND: Family planning has been defined in the framework of mothers and
      children plan as one of Primary Healthcare (PHC) details. Besides quantity, the
      quality of services, particularly in terms of ethics, such as observing
      individuals' privacy, is of great importance in offering family planning
      services. OBJECTIVE: A preliminary study to gather information about the degree
      of medical ethics offered during family planning services at Tehran urban
      healthcare centers. MATERIALS AND METHODS: A questionnaire was designed for
      study. In the first question regarding informed consent, 47 clients who were
      advised about various contraception methods were asked whether advantages and
      disadvantages of the contraceptive methods have been discussed by the service
      provider. Then a certain rank was measured for either client or method in 2007.
      Finally, average value of advantage and disadvantage for each method was
      measured. In questions about autonomy, justice and beneficence, yes/no answers
      have been expected and measured accordingly. RESULTS: Health care providers have
      stressed more on the advantages of pills and disadvantages of tubectomy and have
      paid less attention to advantages of injection ampoules and disadvantages of
      pills in first time clients. While they have stressed more on the advantages and
      disadvantages of tubectomy and less attention to advantages of condom and
      disadvantages of vasectomy in second time clients. Clients divulged their 100%
      satisfaction in terms of observing turns and free charges services. Observance
      degree of autonomy was 64.7% and 77.3% for first time and second- time clients
      respectively. CONCLUSION: Applying the consultant's personal viewpoint for
      selecting a method will breach an informed consent for first and second time
      clients. System has good consideration to justice and no malfeasance.

PMID- 25587252
TI  - Semen characteristics and sperm morphological studies of the West African Dwarf
      Buck treated with Aloe vera gel extract.
AB  - BACKGROUND: Aloe vera (Aloe barbadensis miller) is an evergreen perennial plant
      widely used in modern herbal practice and is often available in proprietary
      herbal preparations. OBJECTIVE: This study was designed to investigate the semen
      picture and spermatozoa morphology of West African Dwarf (WAD) bucks treated with
      Aloe vera extract. MATERIALS AND METHODS: Twelve sexually matured WAD bucks,
      weighing between 11 and 15 kg, were used for the study. The bucks were first used
      as control (pre-treatment) and later as two groups of six animals each. The first
      six bucks received 10 mls of the 3% extract while the other six received 10 mls
      of the 4% of the extract for a 7 day period. Semen was collected from both the 3
      and 4% extract treated bucks for the control (pre-treatment), on days eight
      (first week post-treatment) and fifteen (second week post-treatment) in each case
      using the electroejaculation method. The spermiogram of the bucks were
      investigated using standard procedures. Data obtained were analyzed using two way
      ANOVA and significance reported at p<0.05. RESULTS: The continuous administration
      of Aloe vera extract significantly (p<0.05) reduced sperm concentration, motility
      and percentage livability and resulted in increased sperm abnormalities in the
      WAD buck. CONCLUSION: Aloe vera adversely affected the spermiogram of bucks. The
      plant can reduce fertility in male animals and is therefore not recommended for
      medicinal purpose in male animals especially those used for breeding.

PMID- 25587253
TI  - Incidence of sexual dysfunction in men after cardiac surgery in Afshar hospital,
      Yazd.
AB  - BACKGROUND: Successful rehabilitation of cardiac surgery patients should include
      consideration of their sexual activity, but there is paucity of data regarding
      this matter. OBJECTIVE: This study determined the incidence and type of sexual
      dysfunction in our patients. MATERIALS AND METHODS: Two hundred-seventy nine men
      with age under 70 years old who had coronary artery bypass graft (CABG),
      valvular, or other types of cardiac surgery from Dec. 2006 until Dec. 2007 were
      enrolled in this descriptive-analytical study. They were interviewed before and
      12 weeks after the operation in regard to the impact of surgery on their
      sexuality. The statistical methods used included analysis of variance, Kappa
      test, and chi-square analysis. RESULTS: The mean age of the patients was 55.7 +/-
      10.66 (25-69) years. The incidence of sexual dysfunction was 20.1% before,
      and76.4%, 12 weeks after the operation. P-valueas tested by Kappa test was
      0.0001, which means that cardiac surgery had adverse effect on sexual activity of
      the patients. Types of sexual dysfunction were impotence, premature ejaculation,
      and decreased or loss of libido in 6.5%, 4.3% and 9.3%, respectively before
      operation, and 34.8%, 21.5% and 20.1%, respectively 12 weeks after the operation.
      Concurrence of more than one dysfunction was not reported. CONCLUSION: Sexual
      dysfunction is common after cardiac surgery, and sexual counseling is still not
      being addressed adequately. The role and responsibility of the physician and the
      rehabilitation nurse becomes evident, together with the need for the patient's
      partner to participate in counseling.

PMID- 25587254
TI  - The effects of laser assisted hatching on pregnancy rates.
AB  - BACKGROUND: For infertile women aged over 35 years, failure of the ZP (zona
      pellucida) to rupture is believed to be associated with a decreased implantation
      rate in in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI).
      OBJECTIVE: In this research, laser assisted hatching (LAH) was offered to
      patients with advanced maternal age to evaluate a possible benefit. MATERIALS AND
      METHODS: Nine hundred thirty two cycles of IVF/ICSI in females were analyzed.
      Women included in this study were allocated in 4 groups. In group I and II,
      embryos were cultured and transferred with and without LAH in women aged <=35,
      whereas embryos of group III and IV were examined with and without LAH in women
      aged >= 35. Laser manipulations were performed using a suturn-Tm3 system using 2
      3 pulses of 0.8 millisecond with 400 voltage duration. The size of the hole made
      in the zona was measured to be 5-10 um, depending on the zona thickness of each
      individual embryo. RESULTS: The performance of LAH significantly increased
      clinical pregnancy rates in all patients. In group I and II, the chemical (50.99%
      and 31.61% respectively), clinical (50% and 30.69% respectively) and multiple
      pregnancies (22.27% and 5.94% respectively) significantly differ between these
      groups. In the patients with advanced female age >=35 the performance of LAH
      significantly increased chemical (30.12%) and clinical pregnancy (27.71%) rates
      compared to whom without LAH (18.96% and 16.37% respectively). CONCLUSION: Our
      data demonstrate in the patients who were less than 35 years old, multiple
      pregnancy rates were significantly increased compared to other groups who aged
      over 35 years old. In addition benefit of LAH in improving pregnancy rates after
      IVF or ICSI in women of advanced age (>=35) was shown.

PMID- 25587255
TI  - The status of depression and anxiety in infertile Turkish couples.
AB  - BACKGROUND: Infertility is a major psychosocial crisis as well as being a medical
      problem. The factors that predict psychosocial consequences of infertility may
      vary in different gender and different infertile populations. OBJECTIVE: The
      primary purpose of this study was to investigate whether Turkish infertile
      couples had higher levels of depression and anxiety when compared to non
      infertile couples. Our secondary aim was to evaluate the relationship between
      sociodemographic characteristics and levels of depression and anxiety in Turkish
      infertile couples. MATERIALS AND METHODS: We designed a descriptive cross
      sectional study of 248 infertile women and 96 infertile men with no psychiatric
      disturbance and 51 women and 40 men who have children to evaluate the depression
      and anxiety levels between infertile couples and fertile couples. A gynecologist
      evaluated participants for demographic data and then they were visited by a
      psychologist to perform questionnaire scales which were The Beck Depression
      Inventory and the State-Trait Anxiety Inventory for the evaluation of the degree
      of psychopathology. The data were statistically analyzed, with p<0.05 as the
      level of statistical significance. RESULTS: We observed significant differences
      between the infertile couples and fertile couples with respect to state and trait
      anxiety (p<0.0001) while no difference was regarding with depression, both of
      women and men. Anxiety and depression were observed as independent from gender
      when infertile women and men were compared (p=0.213). CONCLUSION: We believed
      that the psychological management at infertile couples must be individualized
      with cultural, religious, and class related aspects.

PMID- 25587256
TI  - Analysis of 232 total fertilization failure cycles during intracytoplasmic sperm
      injection.
AB  - BACKGROUND: The intracytoplasmic sperm injection procedure ending with total
      fertilization failure is very distressfull event for both the clinician and the
      patient. OBJECTIVE: The aim of this study was to identify independent factors
      which could be used to identify total fertilization failure before the day of
      intracytoplasmic sperm injection. MATERIALS AND METHODS: This was a retrospective
      study of 232 patients who were admitted to a tertiary-care hospital IVF Unit and
      showed total fertilization failure during intracytoplasmic sperm injection
      cycles. To sort out the interwined effects of female age, basal FSH, sperm
      quality, antral follicle count, starting dose of gonadotrophine, sperm extraction
      technique, cycle length, >14 mm follicle number, oocyte number after oocyte pick
      up, estradiol and progesterone level on the day of hCG and the MI, MII and GV
      oocyte number on the fertilization, multiple logistic regression analysis was
      used. RESULTS: The total fertilization failure rate was 6% and the recurrance
      rate was 23%. The original model illustrated that the presence of GV oocytes,
      total oocyte number less than six, <2000 pg/mL E2 concentration on the day of hCG
      and testicular sperm extraction increases the total fertilization failure risk.
      CONCLUSION: It is very difficult to predict total fertilization failure.
      Sometimes even with one good quality oocyte and sperm and in the case of
      globozoospermia fertilization can be achieved. Not only azoospermia but also low
      oocyte numbers increase the chance of total fertilization failure even after
      intracytoplasmic sperm injection.

PMID- 25587257
TI  - Lipid peroxidation is not associated with adipocytokines in preeclamptic women.
AB  - BACKGROUND: The association between lipid peroxidation biomarkers and
      adipocytokines is hypothesized in preeclampsia but little is known about it.
      OBJECTIVE: he present study was undertaken to determine the association of lipid
      peroxidation biomarkers measured by the levels of 8-isoprostane and
      malondialdehyde with adipocytokines leptin and adiponectin in maternal serum of
      preeclamptic women. MATERIALS AND METHODS: A cross-sectional study was designed.
      The study population consisted of 30 preeclamptic patients and 30 healthy
      pregnant women. Serum levels of 8-Isoprostane, total leptin and total adiponectin
      were assessed using commercially available enzyme-linked immunosorbent assay
      methods. The amount of malondialdehyde was determined by the thiobarbituric acid
      assay. Mann-Whitney U test and Spearman's correlation coefficient were used for
      statistical analysis. RESULTS: Both 8-Isoprostane and malondialdehyde were
      significantly higher in preeclamptic group than those in normal pregnant women.
      Serum levels of leptin were significantly increased in preeclamptic patients
      compared with normal group, while adiponectin levels were decreased. Serum levels
      of 8-Isoprostane and malondialdehyde did not show any significant correlation
      with leptin and adiponectin. CONCLUSION: In preeclamptic women, maternal serum
      levels of leptin and adiponectin were not correlated with lipid peroxidation.

PMID- 25587258
TI  - Comparing intramuscular progesterone, vaginal progesterone and 17 
      hydroxyprogestrone caproate in IVF and ICSI cycle.
AB  - BACKGROUND: Supplementation of luteal phase with progesterone is prescribed for
      women undergoing routine IVF treatment. OBJECTIVE: The objective of this study
      was to compare the efficacy of three types of progesterone on biochemical,
      clinical and ongoing pregnancy rates and abortion and live birth rates. MATERIALS
      AND METHODS: A prospective randomized study was performed at Royan Institute
      between March 2008 and March 2009 in women under 40 years old, who use GnRH
      analog down-regulation. One hundred eighty six patients in three groups were
      received progesterone in oil (100 mg, IM daily), intravaginal progesterone (400
      mg, twice daily) and 17-alpha hydroxyprogestrone caproate (375mg, every three
      days), respectively. RESULTS: Final statistical analysis after withdrawal of some
      patients was performed in 50, 50 and 53 patients in group 1, 2 and 3
      respectively. No differences between the groups were found in baseline
      characteristics. No statistical significance different was discovered for
      biochemical, clinical and ongoing pregnancies. Although the abortion rate was
      statistically higher in group 1 (p=0.025) the live birth rate was not
      statistically significant between the three groups. CONCLUSION: The effects of
      three types of progesterone were similar on pregnancies rate. We suggest the use
      of intravaginal progesterone during the luteal phase in patients undergoing an
      IVF-ET program because of the low numbers of abortions, and high ongoing
      pregnancy rates.

PMID- 25587259
TI  - Effects of sera taken from women with recurrent spontaneous abortion on sperm
      motility and apoptosis.
AB  - BACKGROUND: Recurrent spontaneous abortion impacts almost 1% of couples. The sera
      from women with unexplained recurrent spontaneous abortion (URSA) have toxic
      effects on embryos that grow in the uterus. Therefore, the abnormal condition of
      the uterus may also affect sperm qualities. OBJECTIVE: The objectives of this
      study were to search if these sera could induce DNA denaturation in sperm nuclei
      and also it could reduce sperm motility. MATERIALS AND METHODS: Sera of 20 women
      with URSA history and sera from 20 women with at least two healthy children were
      added to the sperms samples from 20 healthy men for 2 hours. The sperm motility
      was assessed after incubation with sera. The samples were stained with Tdt
      mediated dUTP nick end labeling (TUNEL) assay for DNA fragmentation. The samples
      were analyzed with flow cytometry and the percentage of the TUNEL positive sperms
      were calculated. The data were analyzed by t-test. RESULTS: The incubation of the
      sperm samples in sera with URSA lead to a decrease in the percentage of the
      motile sperm from 55% in control to 41% in the treated group, significantly
      (p=0.038). The percentage of the sperm with abnormal fragmented DNA increased
      after incubation with URSA (26.6%) compare to the control (21.2%); however, it
      was not significant. CONCLUSION: It seems that sera from URSA patients could not
      induce a significant increase in the percentage of the sperms with nuclei contain
      DNA fragmentation. However, the sera of women with URSA could affect the
      fertility rate by reduction of the sperm motility.

PMID- 25587260
TI  - Comparison of maternal and neonatal serum leptin levels in preeclampsia and
      normal pregnancy.
AB  - BACKGROUND: Leptin is a protein product of obesity gene and is synthesized mainly
      by adipose tissue. OBJECTIVE: The aim of this study was to determine maternal and
      neonatal serum leptin levels in term preeclamptic and normal pregnancies.
      MATERIALS AND METHODS: This cross sectional study was performed on 37
      preeclamptic and 40 normotensive term pregnant women without other disease. Serum
      level of leptin was measured in all of pregnant mothers and after delivery, their
      neonates. This study was performed in Babol Yahyanejad Hospital from March 2006
      to December 2006. RESULTS: Infants with preeclamptic mothers had significantly
      lower leptin level than control group (p=0.02). There was no significant
      difference in serum leptin levels between normal and preeclamptic women
      (p=0.749). CONCLUSION: According to the results, it would be concluded that
      leptin level in infants of preeclamptic mothers is lower than infants of normal
      mothers. This can only confirm the diagnosis of disease after birth but it cannot
      predict the preeclampsia.

PMID- 25587262
TI  - Reconstructive metroplastic myomectomy of an infertile woman.
AB  - BACKGROUND: While myoma is the most common pelvic mass of women, most women do
      not seek screening tests for uterine myoma and if they have any fibroid they are
      not volunteer for its surgical removal. CASE: We present here a novel technique
      of vascular skeletonization to preserve uterus, making pregnancy possible for an
      infertile woman with a large uterine myoma, situated in the uterine lower
      segment. CONCLUSION: Vascular skeletonization to preserve vessels for a case of
      myomectomy helped preserve the patient's ability to conceive.

PMID- 25587261
TI  - Unexplained infertility as primary presentation of celiac disease, a case report
      and literature review.
AB  - BACKGROUND: Celiac sprue (gluten sensitive enteropathy) is an autoimmune disease
      which is hereditary and its pathology mainly bases on immunologic intolerance to
      gluten. It has a vast variety of signs and symptoms and its clinical features
      range from a silent disease to a typical gastrointestinal disorder. In this study
      we reviewed and summarized some other related issues about this disease and its
      relation with infertility. CASE: The case is a 26 years old lady who had referred
      to a gynecologist because of infertility for 2 years and later it revealed that
      she has celiac sprue. CONCLUSION: Screening for its silent or subtle types
      especially among suspicious cases such as unexplained infertility seems to be a
      cost effective action. Meanwhile, in time administration of a gluten-free diet
      can lead to an almost complete cure.

PMID- 25587263
TI  - Semen banking: consideration on viral contamination in the era of new emerging
      viral infection.

PMID- 25587264
TI  - Computer-assisted segmentation of videocapsule images using alpha-divergence
      based active contour in the framework of intestinal pathologies detection.
AB  - Visualization of the entire length of the gastrointestinal tract through natural
      orifices is a challenge for endoscopists. Videoendoscopy is currently the "gold
      standard" technique for diagnosis of different pathologies of the intestinal
      tract. Wireless capsule endoscopy (WCE) has been developed in the 1990s as an
      alternative to videoendoscopy to allow direct examination of the gastrointestinal
      tract without any need for sedation. Nevertheless, the systematic postexamination
      by the specialist of the 50,000 (for the small bowel) to 150,000 images (for the
      colon) of a complete acquisition using WCE remains time-consuming and challenging
      due to the poor quality of WCE images. In this paper, a semiautomatic
      segmentation for analysis of WCE images is proposed. Based on active contour
      segmentation, the proposed method introduces alpha-divergences, a flexible
      statistical similarity measure that gives a real flexibility to different types
      of gastrointestinal pathologies. Results of segmentation using the proposed
      approach are shown on different types of real-case examinations, from
      (multi)polyp(s) segmentation, to radiation enteritis delineation. 

PMID- 25587265
TI  - Improvement of adaptive GAs and back propagation ANNs performance in condition
      diagnosis of multiple bearing system using grey relational analysis.
AB  - Condition diagnosis of multiple bearings system is one of the requirements in
      industry field, because bearings are used in many equipment and their failure can
      result in total breakdown. Conditions of bearings commonly are reflected by
      vibration signals data. In multiple bearing condition diagnosis, it will involve
      many types of vibration signals data; thus, consequently, it will involve many
      features extraction to obtain precise condition diagnosis. However, large number
      of features extraction will increase the complexity of the diagnosis system.
      Therefore, in this paper, we presented a diagnosis method which is hybridization
      of adaptive genetic algorithms (AGAs), back propagation neural networks (BPNNs),
      and grey relational analysis (GRA) to diagnose the condition of multiple bearings
      system. AGAs are used in the diagnosis algorithm to determine the best initial
      weights of BPNNs in order to improve the diagnosis accuracy. In addition, GRA is
      applied to determine and select the dominant features from the vibration signal
      data which will provide good diagnosis of multiple bearings system in less
      features extraction. The experiments results show that AGAs-BPNNs with GRA
      approaches can increase the accuracy of diagnosis in shorter processing time,
      compared with the AGAs-BPNNs without the GRA. 

PMID- 25587266
TI  - Application of wireless intelligent control system for HPS lamps and LEDs
      combined illumination in road tunnel.
AB  - Because of the particularity of the environment in the tunnel, the rational
      tunnel illumination system should be developed, so as to optimize the tunnel
      environment. Considering the high cost of traditional tunnel illumination system
      with high-pressure sodium (HPS) lamps as well as the effect of a single light
      source on tunnel entrance, the energy-saving illumination system with HPS lamps
      and LEDs combined illumination in road tunnel, which could make full use of these
      two kinds of lamps, was proposed. The wireless intelligent control system based
      on HPS lamps and LEDs combined illumination and microcontrol unit (MCU) Si1000
      wireless communication technology was designed. And the remote monitoring,
      wireless communication, and PWM dimming module of this system were designed
      emphatically. Intensity detector and vehicle flow detector can be configured in
      wireless intelligent control system, which gather the information to the master
      control unit, and then the information is sent to the monitoring center through
      the Ethernet. The control strategies are got by the monitoring center according
      to the calculated results, and the control unit wirelessly sends parameters to
      lamps, which adjust the luminance of each segment of the tunnel and realize the
      wireless intelligent control of combined illumination in road tunnel. 

PMID- 25587267
TI  - A study on urban road traffic safety based on matter element analysis.
AB  - This paper examines a new evaluation of urban road traffic safety based on a
      matter element analysis, avoiding the difficulties found in other traffic safety
      evaluations. The issue of urban road traffic safety has been investigated through
      the matter element analysis theory. The chief aim of the present work is to
      investigate the features of urban road traffic safety. Emphasis was placed on the
      construction of a criterion function by which traffic safety achieved a
      hierarchical system of objectives to be evaluated. The matter element analysis
      theory was used to create the comprehensive appraisal model of urban road traffic
      safety. The technique was used to employ a newly developed and versatile matter
      element analysis algorithm. The matter element matrix solves the uncertainty and
      incompatibility of the evaluated factors used to assess urban road traffic
      safety. The application results showed the superiority of the evaluation model
      and a didactic example was included to illustrate the computational procedure. 

PMID- 25587268
TI  - Metabolic changes and serum ghrelin level in patients with psoriasis.
AB  - Background. Serum ghrelin levels may be related to metabolic and clinical changes
      in patients with psoriasis. Objective. This study was performed to determine the
      possible effects of serum ghrelin in patients with psoriasis. Methods. The study
      population consisted of 25 patients with plaque psoriasis. The patients were
      questioned with regard to age, gender, age of onset, duration of disease, height,
      weight, and body mass index (BMI). In addition, fasting blood sugar,
      triglyceride, cholesterol levels, insulin, and ghrelin levels were measured.
      Results. The mean serum ghrelin level was 45.41 +/- 22.41 in the psoriasis group
      and 29.92 +/- 14.65 in the healthy control group. Serum ghrelin level was
      significantly higher in the psoriasis group compared with the controls (P =
      0.01). The mean ghrelin level in patients with a lower PASI score was
      significantly higher than in those with a higher PASI score (P = 0.02).
      Conclusion. The present study was performed to determine the effects of ghrelin
      in psoriasis patients. We found a negative correlation between severity of
      psoriasis and ghrelin level. Larger and especially experimental studies focusing
      on correlation of immune system-ghrelin levels and severity of psoriasis may be
      valuable to clarify the etiopathogenesis of the disease. 

PMID- 25587269
TI  - Prognostic Value of AIMS65 Score in Cirrhotic Patients with Upper
      Gastrointestinal Bleeding.
AB  - Introduction. Unlike Rockall scoring system, AIMS65 is based only on clinical and
      laboratory features. In this study we investigated the correlation between the
      AIMS65 score and Endoscopic Rockall score, in cirrhotic and noncirrhotic
      patients. Methods. This is a retrospective study of patients admitted with overt
      UGIB and undergoing esophagogastroduodenoscopy (EGD). AIMS65 and Rockall scores
      were calculated at the time of admission. We investigated the correlation between
      both scores along with stigmata of bleed seen on endoscopy. Results. A total of
      1255 patients were studied. 152 patients were cirrhotic while 1103 patients were
      noncirrhotic. There was significant correlation between AIMS65 and Total Rockall
      scores in patients of both groups. There was significant correlation between
      AIMS65 score and Endoscopic Rockall score in noncirrhotics but not cirrhotics.
      AIMS65 scores in both cirrhotic and noncirrhotic groups were significantly higher
      in patients who died from UGIB than in patients who did not. Conclusion. We
      observed statistically significant correlation between AIMS65 score and length of
      hospitalization and mortality in noncirrhotic patients. We found that AIMS65
      score paralleled the endoscopic grading of lesion causing UGIB in noncirrhotics.
      AIMS65 score correlated only with mortality but not the length of hospitalization
      or endoscopic stigmata of bleed in cirrhotics. 

PMID- 25587270
TI  - Factors Associated with Insomnia among Elderly Patients Attending a Geriatric
      Centre in Nigeria.
AB  - Background. Insomnia is a form of chronic sleep problem of public health
      importance which impacts the life of elderly people negatively. Methods. Cross
      sectional study of 843 elderly patients aged 60 years and above who presented
      consecutively at Geriatric Centre, University College Hospital, Ibadan, Nigeria.
      The World Health Organization Composite International Diagnostic Interview was
      used to diagnose insomnia. We assessed the following candidate variables which
      may be associated with insomnia such as socidemographic characteristics,
      morbidities, and lifestyle habits. Statistical analysis was done with SPSS 17.
      Results. The point prevalence of insomnia was 27.5%. Insomnia was significantly
      associated with being female, not being currently married, having formal
      education, living below the poverty line, and not being physically active. Health
      complaints of abdominal pain, generalized body pain, and persistent headaches
      were significantly associated with insomnia. Conclusion. The high prevalence of
      insomnia among elderly patients in this setting calls for concerted effort by
      healthcare workers to educate the elderly on lifestyle modification. 

PMID- 25587271
TI  - Serum leptin levels in polycystic ovary syndrome and its relationship with
      metabolic and hormonal profile in pakistani females.
AB  - The study aimed to investigate the levels of serum leptin in PCOS females and to
      correlate it with metabolic and hormonal parameters. Sixty-two PCOS and ninety
      normal cycling (NC) females with matched age and body mass index (BMI) were
      recruited for this cross-sectional study. Serum leptin, FSH, LH, E2, free
      testosterone, progesterone, thyroid profile, and FBG levels were measured. The
      mean leptin levels in PCOS and NC were not significantly different (45.56 ng/mL
      +/- 1.49 vs 41.78 +/- 1.31 ng/mL, P > 0.05); however, leptin levels showed a
      strong correlation with BMI in PCOS and NC group (r = 0.77, P < 0.0001; r = 0.82,
      P < 0.0001, resp.). High E2 levels in NC had a significant correlation with
      leptin whereas FBG correlated with leptin in PCOS (r = 0.51, P = 0.005). TSH had
      a substantial correlation (r = 0.49, P < 0.005; r = 0.69, P < 0.005) in PCOS and
      NC, respectively. There was no significant difference found in circulating leptin
      concentration between PCOS and NC subjects. Leptin levels in PCOS were related
      with metabolic impairments manifested by disturbance in FBG levels and impairment
      of reproductive functions in terms of reduced E2 secretion. 

PMID- 25587272
TI  - Regulation of UCP1 in the Browning of Epididymal Adipose Tissue by beta3
      Adrenergic Agonist: A Role for MicroRNAs.
AB  - Background. White adipose tissue browning may be a promising strategy to combat
      obesity. UCP1 is strongly induced in White adipose tissue with beta3-adrenergic
      agonist treatment, but the causes of this increase have not been fully
      elucidated. This study aims to explore more miRNAs involved in the process of
      browning of visceral adipose tissue. Methods. Total of fourteen mice were
      randomly divided into control and study group. Study group mice were injected
      intraperitoneally with CL316243 once daily for seven days; meanwhile the control
      group were treated with 0.9% NaCl. After a 7-day period, the expression of genes
      involved in WAT browning and potential UCP1-targeting miRNAs in adipose tissues
      was analyzed by qPCR. Results. qPCR analysis revealed that UCP1, DIO2, CIDEA, and
      CPT1B in epididymal adipose tissue were overexpressed in CL316243 group.
      Furthermore, potential UCP1-targeting miR-9 and miR-338-3p in epididymal adipose
      tissue were significantly decreased in CL316243 group. Conclusion. This suggests
      that potential UCP1-targeting miR-9 and miR-338-3p may be involved in the
      browning of epididymal adipose tissue by regulating UCP1 gene expression. In this
      study, we demonstrated that this increase of UCP1 is due, at least in part, to
      the decreased expression of certain UCP1-targeting miRNAs in epididymal adipose
      tissue compared to control. 

PMID- 25587273
TI  - Reevaluation of Acromegalic Patients in Long-Term Remission according to Newly
      Proposed Consensus Criteria for Control of Disease.
AB  - Acromegaly guidelines updated in 2010 revisited criteria of disease control: if
      applied, it is likely that a percentage of patients previously considered as
      cured might present postglucose GH nadir levels not adequately suppressed, with
      potential implications on management. This study explored GH secretion, as well
      as hormonal, clinical, neuroradiological, metabolic, and comorbid profile in a
      cohort of 40 acromegalic patients considered cured on the basis of the previous
      guidelines after a mean follow-up period of 17.2 years from remission, in order
      to assess the impact of the current criteria. At the last follow-up visit, in the
      presence of normal IGF-I concentrations, postglucose GH nadir was over 0.4 MUg/L
      in 11 patients (Group A) and below 0.4 MUg/L in 29 patients (Group B); moreover,
      Group A showed higher basal GH levels than Group B, whereas a significant decline
      of both GH and postglucose GH nadir levels during the follow-up was observed in
      Group B only. No differences in other evaluated parameters were found. These
      results seem to suggest that acromegalic patients considered cured on the basis
      of previous guidelines do not need a more intensive monitoring than patients who
      met the current criteria of disease control, supporting instead that the cut-off
      of 0.4 mcg/L might be too low for the currently used GH assay. 

PMID- 25587274
TI  - Interpreting the consequences of metformin accumulation in an emergency context:
      impact of the time frame on the blood metformin levels.
AB  - Objective. To clarify the link between metformin accumulation and its metabolic
      consequences by taking the time frame for metformin measurement into account.
      Research Design and Methods. Our database was studied for cases of metformin
      accumulation and lactic acidosis status available on admission, and then we
      selected patients in whom arterial pH, blood lactate, and plasma and erythrocyte
      metformin levels had been determined at the same time point. Results. Seventeen
      reports were studied on 16 patients, of whom 10 presented lactic acidosis. The
      time interval between admission and comprehensive testing ranged from 0 to 52
      hours. The study parameters were determined simultaneously on admission in only 4
      patients. In the 9 patients with lactic acidosis on admission and a delayed
      metformin assay, lactic acidosis persisted in 6 cases and had resolved in 3 cases
      by the time the blood sampling for metformin assay was performed. Conversely,
      lactic acidosis developed after admission in one case. Conclusions. Caution must
      be taken when interpreting the consequences of metformin accumulation in an
      emergency context: the patient's lactic acidosis status will have changed by the
      time the metformin assay is performed, even though metformin accumulation may
      still be present. 

PMID- 25587276
TI  - Accelerated Tooth Movement and Temporary Skeletal Anchorage Devices (TSADs).

PMID- 25587275
TI  - Systematic Review of Surgical Approaches for Adrenal Tumors: Lateral
      Transperitoneal versus Posterior Retroperitoneal and Laparoscopic versus Robotic
      Adrenalectomy.
AB  - Background. Laparoscopic lateral transperitoneal adrenalectomy (LTA) has been the
      standard method for resecting benign adrenal gland tumors. Recently, however,
      laparoscopic posterior retroperitoneal adrenalectomy (PRA) has been more popular
      as an alternative method. This systematic review evaluates current evidence on
      adrenalectomy techniques, comparing laparoscopic LTA with PRA and laparoscopic
      adrenalectomy with robotic adrenalectomy. Methods. PubMed, Embase, and ISI Web of
      Knowledge databases were searched systematically for studies comparing surgical
      outcomes of laparoscopic LTA versus PRA and laparoscopic versus robotic
      adrenalectomy. The studies were evaluated according to the PRISMA statement.
      Results. Eight studies comparing laparoscopic PRA and LTA showed that
      laparoscopic PRA was superior or at least comparable to laparoscopic LTA in
      operation time, blood loss, pain score, hospital stay, and return to normal
      activity. Conversion rates and complication rates were similar. Six studies
      comparing robotic and laparoscopic adrenalectomy found that outcomes and
      complications were similar. Conclusion. Laparoscopic PRA was more effective than
      LTA, especially in reducing operation time and hospital stay, but there was no
      evidence showing that robotic adrenalectomy was superior to laparoscopic
      adrenalectomy. Cost reductions and further technical advances are needed for
      wider application of robotic adrenalectomy. 

PMID- 25587277
TI  - Current controversies in classification, management, and prevention of
      bisphosphonate-related osteonecrosis of the jaw.

PMID- 25587278
TI  - Ciprofloxacin release using natural rubber latex membranes as carrier.
AB  - Natural rubber latex (NRL) from Hevea brasiliensis is easily manipulated, low
      cost, is of can stimulate natural angiogenesis and cellular adhesion, is a
      biocompatible, material and presents high mechanical resistance. Ciprofloxacin
      (CIP) is a synthetic antibiotic (fluoroquinolone) used in the treatment of
      infection at external fixation screws sites and remote infections, and this use
      is increasingly frequent in medical practice. The aim of this study was to
      develop a novel sustained delivery system for CIP based on NRL membranes and to
      study its delivery system behavior. CIP was found to be adsorbed on the NRL
      membrane, according to results of energy dispersive X-ray spectroscopy. Results
      show that the membrane can release CIP for up to 59.08% in 312 hours and the
      mechanism is due to super case II (non-Fickian). The kinetics of the drug release
      could be fitted with double exponential function X-ray diffraction and Fourier
      transform infrared (FTIR) spectroscopy shows some interaction by hydrogen bound,
      which influences its mechanical behavior. 

PMID- 25587280
TI  - Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance
      Selection on the Metabolic Activities and Drug Susceptibilities of Clostridium
      perfringens Strains.
AB  - Fluoroquinolone resistance affects toxin production of Clostridium perfringens
      strains differently. To investigate the effect of fluoroquinolone resistance
      selection on global changes in metabolic activities and drug susceptibilities,
      four C. perfringens strains and their norfloxacin-, ciprofloxacin-, and
      gatifloxacin-resistant mutants were compared in nearly 2000 assays, using
      phenotype microarray plates. Variations among mutant strains resulting from
      resistance selection were observed in all aspects of metabolism. Carbon
      utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant
      strains were affected differently in the resistant mutants depending on both the
      bacterial genotype and the fluoroquinolone to which the bacterium was resistant.
      The susceptibilities to gentamicin and erythromycin of all resistant mutants
      except one increased, but some resistant strains were less susceptible to
      amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than
      their wild types. Sensitivity to ethidium bromide decreased in some resistant
      mutants and increased in others. Microarray analysis of two gatifloxacin
      resistant mutants showed changes in metabolic activities that were correlated
      with altered expression of various genes. Both the chemical structures of
      fluoroquinolones and the genomic makeup of the wild types influenced the changes
      found in resistant mutants, which may explain some inconsistent reports of the
      effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria. 

PMID- 25587279
TI  - Determination of oxidative stress related toxicity on repeated dermal exposure of
      hydroxyapatite nanoparticles in rats.
AB  - Hydroxyapatite nanoparticles (HANPs) have numerous applications, such as
      substitute for bone grafting, bone fillers, bioceramic coating, and dental
      fillings. The toxicity of these nanomaterials is of growing concern despite their
      significant scientific interest and promising potential in many applications. In
      this study, an in-house synthesized, characterized HANP of size <50 nm was
      investigated for the dermal toxicity. A paste of HANPs was prepared in water and
      applied on the dorsal side of the rats for 28 days. At the end of 28 days, blood
      was subjected to haematological and biochemical analysis. Gross necropsy was
      conducted and major organs were collected for histopathological observations.
      Liver from the animals was evaluated for lipid peroxidation, reduced glutathione,
      and antioxidant enzymes activity. It was observed that none of the animals showed
      any abnormality during the experimental period. Gross examination of carcasses
      did not reveal any abnormality in the organs examined. The results also
      demonstrated that there was no significant fluctuation in the level of
      antioxidant defense mechanisms, lipid peroxidation, and haematological and
      biochemical parameters. There was no histopathological lesion observed in any of
      the organs. Hence, it can be concluded that the synthesized HANPs were nontoxic
      at cellular level, when exposed dermally to rats. 

PMID- 25587281
TI  - Chronic pulmonary aspergillosis complicating bronchial atresia.
AB  - Bronchial atresia is a rare pulmonary developmental anomaly characterized by the
      presence of a focal obliteration of a segmental or lobar bronchial lumen. The
      lung distal to the atretic bronchus is typically emphysematous along with the
      presence of mucus filled ectatic bronchi (mucoceles). BA is usually asymptomatic
      but pulmonary infections can rarely develop in the emphysematous lung distal to
      the atretic bronchus. We present a unique case of chronic pulmonary aspergillosis
      (CPA) in a patient with BA with no evidence of immune dysfunction. The patient
      was treated initially with voriconazole and subsequently underwent surgical
      excision of the involved area. On follow-up, she has done extremely well with no
      evidence for recurrence. In summary, we describe the first case of chronic
      pulmonary aspergillosis in an immunocompetent patient with bronchial atresia. 

PMID- 25587282
TI  - Maraviroc Failed to Control Progressive Multifocal Leukoencephalopathy-Associated
      IRIS in a Patient with Advanced HIV Infection.
AB  - Due to the lack of therapeutic options for patients with progressive multifocal
      leukoencephalopathy-associated immune reconstitution inflammatory syndrome (PML
      associated IRIS), maraviroc has generated expectations among the medical
      community. However, we report a patient with advanced HIV infection, who
      developed PML-associated IRIS and had a fatal outcome despite the addition of
      maraviroc to suppressive ART. Future studies are required to define the
      therapeutic role of maraviroc in PML-associated IRIS and differentiate
      individuals who may benefit from maraviroc from those who may develop
      neurological deterioration. 

PMID- 25587284
TI  - Efficient and cost-effective alternative treatment for recurrent urinary tract
      infections and interstitial cystitis in women: a two-case report.
AB  - Urinary tract infections (UTIs) are among the most common bacterial infections
      affecting women. UTIs are primarily caused by Escherichia coli, which increases
      the likelihood of a recurrent infection. We encountered two cases of recurrent
      UTIs (rUTIs) with a positive E. coli culture, not improving with antibiotics due
      to the development of antibiotic resistance. An alternative therapeutic regimen
      based on parsley and garlic, L-arginine, probiotics, and cranberry tablets has
      been given. This regimen showed a significant health improvement and symptoms
      relief without recurrence for more than 12 months. In conclusion, the case
      supports the concept of using alternative medicine in treating rUTI and as a
      prophylaxis or in patients who had developed antibiotic resistance. 

PMID- 25587283
TI  - Metastasis to sartorius muscle from a muscle invasive bladder cancer.
AB  - Bladder cancer constitutes the ninth most common cancer worldwide and
      approximately only 30% of cases are muscle invasive at initial diagnosis.
      Regional lymph nodes, bones, lung, and liver are the most common metastases from
      bladder cancer and generally from genitourinary malignancies. Muscles constitute
      a rare site of metastases from distant primary lesions even though they represent
      50% of total body mass and receive a large blood flow. Skeletal muscles from
      urothelial carcinoma are very rare and up to date only few cases have been
      reported in the literature. We present a rare case of 51-year-old patient with
      metastases to sartorius muscle 8 months after the radical cystectomy performed
      for a muscle invasive bladder cancer. 

PMID- 25587285
TI  - A giant left atrial myxoma.
AB  - Atrial myxomas are the most common primary cardiac tumors. Patients with left
      atrial myxomas generally present with mechanical obstruction of blood flow,
      systemic embolization, and constitutional symptoms. We present a case of an
      unusually large left atrial myxoma discovered incidentally in a patient with
      longstanding dyspnea being managed as bronchial asthma. 

PMID- 25587288
TI  - Nonpharmacological treatment of rhinoconjunctivitis and rhinosinusitis.

PMID- 25587286
TI  - Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly
      Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model.
AB  - We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient
      receptor potential cation channel (TRPC) 1 protein expression can suppress
      hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6
      mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and
      group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure
      (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights
      were increased in group 2 than in group 1 and reduced in group 3 compared with
      group 2. Pulmonary crowded score showed similar pattern, whereas number of
      alveolar sacs exhibited an opposite pattern compared to that of RVSP in all
      groups. Protein expressions of TRPCs, HIF-1alpha, Ku-70, apoptosis, and fibrosis
      and pulmonary mRNA expressions of inflammatory markers were similar pattern,
      whereas protein expressions of antifibrosis and VEGF were opposite to the pattern
      of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle
      proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions
      of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas
      sarcomere length showed an opposite pattern compared to that of RVSP in all
      groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression,
      thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling. 

PMID- 25587287
TI  - Directing parthenogenetic stem cells differentiate into adipocytes for
      engineering injectable adipose tissue.
AB  - The selection of appropriate seed cells is crucial for adipose tissue
      engineering. Here, we reported the stepwise induction of parthenogenetic
      embryonic stem cells (pESCs) to differentiate into adipogenic cells and its
      application in engineering injectable adipose tissue with Pluronic F-127. pESCs
      had pluripotent differentiation capacity and could form teratomas that include
      the three primary germ layers. Cells that migrated from the embryoid bodies (EBs)
      were selectively separated and expanded to obtain embryonic mesenchymal stem
      cells (eMSCs). The eMSCs exhibited similar cell surface marker expression
      profiles with bone morrow mesenchymal stem cells (BMSCs) and had multipotent
      differentiation capacity. Under the induction of dexamethasone, indomethacin, and
      insulin, eMSCs could differentiate into adipogenic cells with increased
      expression of adipose-specific genes and oil droplet depositions within the
      cytoplasm. To evaluate their suitability as seed cells for adipose tissue
      engineering, the CM-Dil labelled adipogenic cells derived from eMSCs were seeded
      into Pluronic F-127 hydrogel and injected subcutaneously into nude mice. Four
      weeks after injection, glistering and semitransparent constructs formed in the
      subcutaneous site. Histological observations demonstrated that new adipose tissue
      was successfully fabricated in the specimen by the labelled cells. The results of
      the current study indicated that pESCs have great potential in the fabrication of
      injectable adipose tissue. 

PMID- 25587289
TI  - A microbiological explanation for the obesity pandemic?

PMID- 25587290
TI  - That other EVD: Enterovirus-D68 - what's it all about?

PMID- 25587291
TI  - Micafungin compared with caspofungin for the treatment of febrile episodes in
      neutropenic patients with hematological malignancies: A retrospective study.
AB  - BACKGROUND: Invasive fungal infections are associated with morbidity and
      mortality in neutropenia secondary to hematological malignancies. Empirical
      antifungal agents are used to reduce their consequences. Caspofungin is the only
      echinocandin approved for this indication. Micafungin was compared with
      caspofungin for the treatment of patients with hematological malignancies and
      prolonged neutropenia. METHODS: A retrospective cohort study was conducted
      involving patients who had hematological malignancies with profound neutropenia
      for a minimum of 10 days, and received empirical micafungin or caspofungin for a
      minimum of five days, between April 2005 and November 2009. Successful outcome
      was based on a composite end point: survival for a minimum of seven days
      following antifungal cessation, successful treatment of baseline fungal
      infection, absence of adverse events and absence of breakthrough fungal
      infection. Fungal infections were defined according to revised definitions of
      invasive fungal disease from the European Organization for Research and Treatment
      of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute
      of Allergy and Infectious Diseases Mycoses Study Group (EORTC-MSG) criteria, with
      modification of the diagnostic imaging criteria. RESULTS: Micafungin had similar
      overall success to caspofungin (60.4% [29 of 48] versus 57.3% [47 of 82],
      respectively; P=0.729). Survival was higher in the micafungin group compared with
      the caspofungin group (100% [48 of 48] versus 89% [73 of 82]; P=0.02). No
      baseline invasive fungal infections were identified in the micafungin group,
      compared with three proven infections treated successfully with caspofungin
      (3.7%; P=0.18). Three proven breakthrough infections were observed in the
      micafungin group (three of 48 [27.3%]) compared with none in the caspofungin
      group (zero of 82; P=0.02). CONCLUSION: Micafungin has similar efficacy to
      caspofungin as empirical antifungal therapy in febrile neutropenic patients with
      hematological malignancies. Verification of these results in a prospective trial
      is warranted.

PMID- 25587292
TI  - Triage and protocol recommendations for the parasitology laboratory based on an
      epidemiological investigation of parasite diagnostics in Ontario laboratories.
AB  - OBJECTIVES: A study was performed using a subset of Ontario laboratory
      parasitology data, with three objectives: to describe parasitic infections in
      Ontario; to identify risk factors for acquiring a parasitic infection using
      routinely collected information; and to use this information to assess current
      protocols for parasite testing in laboratories and, in turn, to propose
      alternatives to optimize the allocation of laboratory resources. METHODS: All
      parasitology records from January 4, 2010 to September 14, 2010 were reviewed
      descriptively and risk factor analyses were performed using information collected
      from requisitions. These results were used to develop preliminary alternative
      protocols, which considered high-throughput screening tests and
      inclusion/exclusion criteria for ova and parasite testing; these were then
      retrospectively analyzed with the dataset to determine appropriateness. RESULTS:
      Of the 29,260 records analyzed, 10% were multiple samples from single patients
      submitted on the same day, of which 98% had the same result. Three percent of all
      parasite tests were positive, with the most prevalent parasites being (in
      ascending order) Dientamoeba fragilis, Giardia lamblia, Cryptosporidium species
      and Entamoeba histolytica/dispar. Age and sex were found to be weak risk factors,
      while rural living was found to be a moderate risk factor for D fragilis, G
      lamblia and Cryptosporidium infections. The strongest risk factor was travel
      history, especially for nonendemic parasites. The retrospective analysis of six
      alternative protocols identified four that may be more efficient than current
      procedures. CONCLUSIONS: The present study demonstrated that current protocols
      may be redundant and can be optimized to target prevalent parasites and
      populations with high risk factors.

PMID- 25587293
TI  - CIHR Canadian HIV Trials Network Co-Infection and Concurrent Diseases Core:
      Updated Canadian guidelines for the treatment of hepatitis C infection in HIV
      hepatitis C coinfected adults.
AB  - BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians
      living with HIV and is responsible for a heavy burden of morbidity and mortality.
      Management of HIV-HCV coinfection is more complex due to the accelerated
      progression of liver disease, the timing and nature of antiretroviral and HCV
      therapy, mental health and addictions management, socioeconomic obstacles and
      drug-drug interactions between new HCV direct-acting antiviral therapies and
      antiretroviral regimens. OBJECTIVE: To update national standards for the
      management of HCV-HIV coinfected adults in the Canadian context. METHODS: A
      standing working group with specific clinical expertise in HIV-HCV coinfection
      was convened by The Canadian Institute of Health Research HIV Trials Network to
      review recently published data regarding HCV antiviral treatments and to update
      the Canadian HIV-HCV coinfection guidelines. RESULTS: Recent data suggest that
      the gap in sustained virological response rates between HCV monoinfection and HIV
      HCV coinfection has been eliminated with newer HCV antiviral regimens. All HIV
      HCV coinfected individuals should be assessed for HCV therapy. First-line
      treatment for genotypes 1 through 6 includes pegylated interferon and weight
      based ribavirin dosing plus the nucleotide sofosbuvir for 12 weeks. Sofosbuvir in
      combination with the protease inhibitor simeprevir is another first-line
      consideration for genotype 1 infection. Sofosbuvir with ribavirin for 12 weeks
      (genotype 2) and 24 weeks (genotype 3) is also recommended as first-line
      treatment. DISCUSSION: Recommendations may not supersede individual clinical
      judgement.

PMID- 25587294
TI  - A 71-year-old woman with recurrent falls and confusion.

PMID- 25587295
TI  - Aches and pains with a shocking rash.

PMID- 25587298
TI  - Parallel import: is it worth?

PMID- 25587297
TI  - The first case of locally acquired tick-borne Babesia microti infection in
      Canada.
AB  - A child with a complicated medical history that included asplenia acquired an
      infection with Babesia microti in the summer of 2013 and had not travelled
      outside of Manitoba. Although the clinical findings were subtle, astute
      laboratory work helped to reach a preliminary identification of Babesia species,
      while reference laboratory testing confirmed the diagnosis. Blacklegged ticks
      (Ixodes scapularis) are known to transmit Borrelia burgdorferi and Anaplasma
      phagocytophilum in the province; however, the present case represents the first
      known instance of tick-borne B microti, both in Manitoba and in Canada. The
      expanding territory of the blacklegged tick increases the relevance of this
      emerging infection. Clinicians, laboratory medical practitioners and public
      health officials should be aware of B microti as a potential locally acquired
      infection in Canada. 

PMID- 25587299
TI  - Preparation, Physicochemical Characterization and I n - vitro Dissolution Studies
      of Diosmin-cyclodextrin Inclusion Complexes.
AB  - Diosmin, a vascular-protecting agent, is practically insoluble in water, and its
      oral absorption is limited by its extremely low dissolution rate. In this study,
      beta-cyclodextrin (betaCD) and 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) were
      obtained to improve the solubility and dissolution rate of diosmin. Phase
      solubility studies of diosmin with betaCD and HPbetaCD in distilled water were
      conducted to characterize the complexes in liquid state. The solid-state
      characterization of the complexes prepared with different methods was performed
      by fourier transform-infra red spectroscopy (FTIR), optical microscopy analyses,
      and differential scanning calorimetry (DSC). Dissolution studies were carried out
      in distilled water using US pharmacopeia dissolution rate testing equipment. The
      complexation of diosmin with betaCD and HPbetaCD both indicated an AL type of
      phase-solubility diagrams, and the apparent stability constants (Kc) was found to
      be 222.13 and 200.08 M(-1), respectively. The Kc values indicated the betaCD and
      HPbetaCD showed the similar equal complexation ability with diosmin, HPbetaCD
      provided higher solubility for diosmin due to its higher water solubility. The
      dissolution studies suggest that the inclusion complexes provide higher
      dissolution rate compared with the physical mixtures and the drug alone.
      Furthermore, the inclusion complex prepared by freeze drying method presented
      higher dissolution rate than kneading method. 

PMID- 25587300
TI  - Preparation, characterization and stability study of dutasteride loaded
      nanoemulsion for treatment of benign prostatic hypertrophy.
AB  - Benign prostatic hyperplasia (BPH)is the most common condition in aging men,
      associated with lower urinary tract symptoms. It is caused due to the augmented
      levels of the androgen dihydrotestosterone. Dutasteride, a 5alpha-Reductase
      inhibitor has been recommended for the treatment of BPH upon oral administration.
      However, long term oral administration of dutasteride may cause sexual problem in
      man. Therefore the main objective of this study was to develop transdermal patch
      having nanoemulsion gel of dutasteride in order to enhance physical and chemical
      stability and eliminate adverse effect of dutasteride. Optimized nanoemulsion was
      prepared by aqueous phase-titration method and characterized by droplet size,
      viscosity and refractive index. In-vitro skin permeation of dutasteride through
      rat abdominal skin was determined by the Franz diffusion cell.Significant
      increase in the steady state flux (J ss), permeability coefficient (K p) and
      enhancement ratio (E r) was observed in optimized nanoemulsion formulation A1 (p
      < 0.05). The Er of optimized nanoemulsion A1 was found to be 1.52 times with
      respect to control which indicates transdermal delivery may be better approach
      for BPH. Stability studies were performed for the period of 3 months. It was
      found that droplet size, viscosity and refractive index were slightly increased
      at refrigerator and room temperature in 3 months period. However, the changes in
      these parameters were not statistically significant (p >= 0.05). The shelf-life
      of optimized nanoemulsion A1 was found to be 2.18 years at room temperature.
      These results indicated that both physical as well as chemical stability of
      dutasteride in nanoemulsion formulation. 

PMID- 25587301
TI  - Effect of zirconium dioxide nanoparticles on glutathione peroxidase enzyme in
      PC12 and n2a cell lines.
AB  - Today, special attention is paid to the use of zirconium dioxide nanoparticle
      (nano-ZrO2), a neutral bioceramic metal, particularly for drug and gene delivery
      in medicine. However, there are some reports implying that use of nano-ZrO2 is
      associated with cytotoxic effects like inhibiting the cell proliferation, DNA
      damage and apoptosis. In the present study, we examined whether nano-ZrO2 alters
      cell viability and glutathione peroxidase (GPx) activity in two neuronal cell
      lines. The PC12 and N2a cells were cultured in the absence or presence of varying
      concentrations (31.25-2000 ug/mL) of nano-ZrO2 for 12, 24 or 48 h. The cell
      viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and GPx
      activity was determined by quantifying the rate of oxidation of the reduced
      glutathione to the oxidized glutathione. Nano-ZrO2 caused a significant reduction
      in cell viability and GPx activity after 12, 24 and 48 h, as compared with
      control group. These effects were concentration dependent and started from 250
      ug/mL. The present study demonstrated that nano-ZrO2, at concentrations of > 250
      ug/mL, has antiproliferative effects via reducing the cell defense mechanism
      against oxidative stress. 

PMID- 25587302
TI  - Evaluation of Lipid-based Drug Delivery System (Phytosolve) on Oral
      Bioavailability of Dibudipine.
AB  - The objective of present study was to evaluate pharmacokinetic parameters of
      dibudipine Phytosolve after oral administration in rats. The solubility test was
      carried out to select suitable oily solvent for dibudipine. Phytosolve
      formulation was prepared with a medium chain triglyceride (MCT) oil (20%),
      soybean phospholipids (5%) and a 70% fructose solution (75%). The effect of
      polyol content on the mean globule size of Phytosolve formulation was studied.
      The optimized formulation was evaluated for robustness toward dilution,
      transparency, droplet size, zeta potential and transmission electron microscopic
      analysis. The Phytosolve of dibudipine with an average droplet size of 142.3 +/-
      4.3 nm and surface charge -18.36 +/- 0.37 mv was administered orally to rats. The
      average relative bioavalabilities of dibudipine in the plasma with Phytosolve
      were 170.4% and 211.2% as compared to the oily solution and aqueous suspension
      respectively. So this formulation could be offered as a useful technique to
      improve the oral delivery of the poorly water soluble drugs such as dibudipine. 

PMID- 25587303
TI  - Preparation of Pluronic/Bile salt/Phospholipid Mixed Micelles as Drug Solubility
      Enhancer and Study the Effect of the PPO Block Size on the Solubility of Pyrene.
AB  - Pluronic/bile salt/phospholipid mixed micelles (Pluronic/BS/PS-MM) drug carrier
      system for solubilization hydrophobic drugs was developed. A typical hydrophobic
      compound, pyrene, was selected as a representative hydrophobic compound to model
      the hydrophobic drugs. Five Pluronics, F68, F88, F98, F108, and F127 with
      different PPO chain length were studied. CMC data and solubilization capacities
      were obtained from a pyrene solubilization method. A closed association model was
      used to obtain the thermodynamic parameters: Gibbs free energy (DeltaG degrees ),
      enthalpy, (DeltaH degrees ) and entropy (DeltaS degrees ) of micellization. The
      results obtained from these experiments suggest that the mixed micelles was more
      stable and solubilize more pyrene than single one; and the solubilization of
      pyrene was strong effected by the PPO block size, thus accentuating synergistic
      interaction mechanism in Pluronic/BS/PS-MM. The study generated an important
      dataset so as to compare the effect of different Pluronics on solubility capacity
      of Pluronic/BS/PS-MM. 

PMID- 25587296
TI  - Therapeutic drug monitoring for triazoles: A needs assessment review and
      recommendations from a Canadian perspective.
AB  - Invasive fungal infections cause significant morbidity and mortality in patients
      with concomitant underlying immunosuppressive diseases. The recent addition of
      new triazoles to the antifungal armamentarium has allowed for extended-spectrum
      activity and flexibility of administration. Over the years, clinical use has
      raised concerns about the degree of drug exposure following standard approved
      drug dosing, questioning the need for therapeutic drug monitoring (TDM).
      Accordingly, the present guidelines focus on TDM of triazole antifungal agents. A
      review of the rationale for triazole TDM, the targeted patient populations and
      available laboratory methods, as well as practical recommendations based on
      current evidence from an extended literature review are provided in the present
      document. 

PMID- 25587304
TI  - Search for the pharmacophore of histone deacetylase inhibitors using
      pharmacophore query and docking study.
AB  - Histone deacetylase inhibitors have gained a great deal of attention recently for
      the treatment of cancers and inflammatory diseases. So design of new inhibitors
      is of great importance in pharmaceutical industries and labs. Creating
      pharmacophor models in order to design new molecules or search a library for
      finding lead compounds is of great interest. This approach reduces the overall
      cost associated with the discovery and development of a new drug. Here we
      elaborated an exact pharmacophore model for histone deacetylase inhibitors by
      using pharmacophore query and docking study. The data set used for the modelling
      exercise comprised of 383 molecules collated from the original literature. These
      molecules were used to crating the model and docking study was held with Zolinza,
      the recently FDA approved drug as potent histone deacetylase inhibitor. Our model
      consists of 5 features: Hydrogen bond donors, Hydrogen bond acceptors, H-bond
      donor/acceptors, Aromatic ring centers, and hydrophobic centers. With the aid of
      this pharmacophore model and docking result, 3D searches in large databases can
      be performed, leading to a significant enrichment of active analogs. 

PMID- 25587305
TI  - Synthesis and Biological Evaluation of Novel Mono Acid Esters Derived from the
      Constituents of Urtica pilulifera.
AB  - New mono acid esters have been synthesized from the reaction of benzoic acid and
      mono-hydroxybenzoic acids with 2-phenoxyethanol separated from Urtica pilulifera,
      characterized, and screened for possible antioxidant, antifungal, antimicrobial
      and anticancer activities. These phenolic acid esters gave various degrees of
      free radical scavenging, but the values were lower than that of alpha-tocopherol.
      The concentrations of the tested compounds needed to reduce DPPH absorption by
      50% at 517 nm were nearly in the range of 900-1100 ug/mL. While for alpha
      tocopherol was 40 ug /mL. The compounds were tested in-vitro against six
      bacterial species which are known to cause dermic and mucosal infections in
      human. 2-phenoxyethyl benzoate showed significant activity in the range of 30%
      against P. aeruginosa to 70% against E. coli compared with the activity of
      Streptomycin. On the other hand 2-phenoxyethyl 2-hydroxybenzoate reveals 70% of
      gentamicin against K. pneumoniae. The tested compounds also showed complete
      inhibition at a concentration less than 37.5 ug/mL against M. canis and less than
      50 ug/mL against T. rubrum. 2-phenoxyethyl 4-hydroxybenzoate showed considerable
      activity against MCF-7 with IC50 is less than 62.5 ug/mL. 

PMID- 25587306
TI  - Synthesis of three rimantadine schiff bases and their biological effects on serum
      albumin.
AB  - Three new rimantadine Schiff bases (RSBs) were prepared, and then the interaction
      of RSBs with bovine serum albumin (BSA) was investigated using fluorescence,
      synchronous fluorescence, UV-vis absorption spectroscopy under physiological
      conditions. The results showed that the three RSBs effectively quenched the
      intrinsic fluorescence of BSA via static quenching. Binding constant (K a),
      number of binding sites (n), and the binding distance (r) between three RSBs and
      BSA were calculated by Stern-Volmer equation and Forster's theory in this study.
      According to the results of displacement experiments of site probes, it was
      considered that the binding sites were located in hydrophobic cavities in sub
      domains IIA of BSA. What is more, synchronous fluorescence studies indicated that
      the hydrophobicity around tryptophan residues was increased with the addition of
      rimantadine-o-vanillin (ROV) and rimantadine-4-methoxy-salicylaldehyde (RMS),
      while there was no apparent change with the addition of rimantadine
      salicylaldehyde (RS). 

PMID- 25587307
TI  - Study on the Multi-marker Components Quantitative HPLC Fingerprint of the
      Compound Chinese Medicine Wuwei Changyanning Granule.
AB  - The aim of this paper is to develop a rapid and highly sensitive quantitative
      HPLC fingerprint method with multiple indicators by using the Compound Chinese
      Medicine Wuwei Changyanning granule and 5 herbs in the prescription. The
      quantitative fingerprint chromatogram with multiple indicators was investigated.
      i)6 compositions included rutin, gallic acid, chlorogenic acid, atractylenolide
      I, pachymic acid and apigenin, which originated from 5 herbs respectively, were
      selected as quantitative compositions, and their contents were determined using
      HPLC from 11 batches granules and the corresponding 5 medicinal materials. ii)
      The precision, stability and repeatability of fingerprinting were investigated.
      In addition, common peaks number, the percentage of non-common peaks and
      similarity were also studied. Among them, 21 common peaks in the granule could
      find the source of peaks from the 5 herbs, among of 10 peaks from Niuerfeng, 9
      peaks from Laliao, 3 peaks from Baishu, 3 peaks from Fuling and 5 peaks from
      Guanghuoxiang. The results showed that the identification method of
      fingerprinting was reliable. 

PMID- 25587308
TI  - RP-HPTLC Retention Data in Correlation with the In-silico ADME Properties of a
      Series of s-triazine Derivatives.
AB  - The properties relevant to pharmacokinetics and pharmacodynamics of four series
      of synthesized s-triazine derivatives have been studied by Quantitative structure
      retention relationship (QSRR) approach. The chromatographic behavior of these
      compounds was investigated by using reversed-phase high performance thin-layer
      chromatography (RP-HPTLC). Chromatographic retention (R M (0)) was correlated
      with selected physicochemical parameters relevant to pharmacokinetics, i.e. ADME
      (absorption, distribution, metabolism and excretion). In addition, the ability to
      act as kinase inhibitors and protease inhibitors was predicted for all
      investigated triazine classes. Also, in order to confirm
      similarities/dissimilarities between series of examined compounds, principal
      component analysis (PCA) based on calculated ADME properties was conducted. The R
      M (0) values of the s-triazine derivatives have been recommended for description
      and evaluation of pharmacokinetic properties. According to results of this study,
      the synthesized s-triazine derivatives meet pharmacokinetic criteria of
      preselection for drug candidates. 

PMID- 25587309
TI  - Meta-analysis of Selective Serotonin Reuptake Inhibitors (SSRIs) Compared to
      Tricyclic Antidepressants (TCAs) in the Efficacy and Safety of Anti-depression
      Therapy in Parkinson's Disease(PD) Patients.
AB  - To assess the efficacy and safety of selective serotonin reuptake
      inhibitors(SSRIs) and tricyclic antidepressants(TCAs) in treatment of
      Parkinsonian depression. A computer-based search was conducted in the databases
      of PUBMED, MEDLINE, EMBASE and CochraneControlled Trails Register up to December
      2011. The random controlled clinic trials about SSRIs and TCAs in treatment of
      Parkinsonian depression were collected. Statistical analysis was completed using
      Review Manager, version 5.0. Five clinic controlled trials were identified for
      this meta-analysis. There was no significant statistical difference in the
      response rate of treatment [RR 0.95, 95%CI (0.78, 1.16)] and Hamilton depression
      score [RR -2.54, 95%CI (-5.35, 0.26)] between two groups. In term of
      complications, no statistical difference was observed in the insomnia rate
      between two groups [RR 0.82, 95%CI (0.24, 2.84)]. Moreover, the incidence rate of
      xerostomia [RR 0.21, 95%CI (0.07, 0.65)] and constipation [RR 0.12, 95%CI(0.02,
      0.63)] was lower in SSRIs group rather than those in TCAs group. In general,
      SSRIs and TCAs have comparable efficacy and equal acceptability in treatment of
      Parkinson's disease-induced depression. However, SSRIs are superior to TCAs in
      the terms of xerostomia and constipation. 

PMID- 25587310
TI  - Effect of a Combination of Omeprazole Plus Sustained Release Baclofen Versus
      Omeprazole Alone on Symptoms of Patients with Gastroesophageal Reflux Disease
      (GERD).
AB  - Previous studies have reported the efficacy of baclofen in the treatment of
      Gastroesophageal Reflux Diseases (GERD). The objective of present study is to
      evaluate the effect of co-administration of omeprazole 20 mg/d plus sustained
      Release baclofen (SR baclofen) vs. omeprazole 20 mg/d plus placebo on alleviation
      of symptoms in patients with a diagnosis of GERD. A prospective, double blind,
      placebo controlled trial included 60 patients with diagnosis of GERD have been
      done. Patients were randomly selected to receive either SR baclofen or a placebo
      in addition to omeprazole 20 mg/d for a period of 2 weeks. Patients were
      questioned regarding heartburn, regurgitation, chest pain and hoarseness at the
      base line and after 2 weeks. All patients tolerated the medications and no
      patients failed to complete the study due to adverse drug reactions. A total of
      53 patients completed the study, 25 in SR baclofen and 28 in placebo group. After
      2 weeks, 1 patient (4%) in SR baclofen group reported heartburn and
      regurgitation. However 13(46.4%) and 15 (53.6%) of patients in the placebo group
      had heartburn and regurgitation respectively. The analysis of the data shows that
      there is a significant difference between the two groups in heartburn and
      regurgitation (p < 0.0001, p < 0.0001 respectively). Statistical analysis
      revealed a significant difference in two groups regarding total GERD score (p
      <0.0001). The results of the present study suggest that a combination of SR
      baclofen and omeprazole may be a more effective treatment for heartburn and
      regurgitation than omeprazole alone. 

PMID- 25587311
TI  - The effects of bupropion on negative symptoms in schizophrenia.
AB  - This study was designed determine the efficacy of bupropion versus placebo in
      subjects with negative symptoms of schizophrenia. A convenience sample of 40
      patients of both genders aged 18-60 years who were living in psychiatric care
      centers were randomly treated with bupropion (started with 75 mg twice a day;
      increased to 100 mg thrice daily) or placebo. The diagnosis of schizophrenia was
      confirmed by a psychiatrist based on Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. Before and after
      the intervention, severity of negative symptoms was determined using a reliable
      and valid Persian version of Scales for the Assessment of Negative Symptoms
      (SANS). Comparison of post-treatment total SANS score and subscale scores between
      bupropion treated patients and placebo group demonstrated no significant
      difference. Moreover, comparison of pre- treatment and post-treatment total SANS
      score and subscales within 2 groups revealed that nor bupropion neither placebo
      improved the severity of negative symptoms significantly. Present study
      demonstrated that bupropion has no significant effect on SANS score of patients
      with severe negative symptoms. However, further studies with larger sample size
      are recommended to achieve more accurate results. 

PMID- 25587312
TI  - Magnesium Sulfate in Exacerbations of COPD in Patients Admitted to Internal
      Medicine Ward.
AB  - The purpose of this study was to examine the effect of intravenous magnesium
      sulfate on patients with COPD exacerbation requiring hospitalization. In this
      randomized clinical trial 30 patients with COPD exacerbation were studied.
      Patients were randomly assigned to group A (case) who concurrent with standard
      therapy received 2 g magnesium sulfate in normal saline infused in 20 minutes on
      days one to three and group B (control) who received standard medications and
      placebo. PEFR and FEV1 were measured by before, 45 minutes and third day of
      entering the study. Vital signs HR, BP, RR, temperature and SpO2 were monitored
      during hospitalization. 21 males and 9 females patients with mean age of 68 +/- 9
      years, case 67 +/- 10 and control 70 +/- 8 were studied (15 patients in each arm
      of study). The mean pretreatment FEV1 was 26% +/- 12, and 35% +/- 18 in case and
      control groups respectively (P=0.137). FEV1 after 45 minutes in case group was
      27% +/- 9 and control group 36% +/- 20 (p=0.122). FEV1 after 3 days of study was
      32% +/- 17 in case and 41% +/- 22 in control groups (P=0.205). The mean
      pretreatment PEFR was 126 +/- 76 l/min in case and 142 +/- 62 l/min in control
      groups (P=0.46). Changes in PEFR were not significant 45 min (p=0.540) and 3 days
      (p=0.733) of the administration of intravenous magnesium sulfate. Duration of
      hospital stay between the two groups did not show any significant difference.
      This study showed that administration of intravenous magnesium sulfate in
      hospitalized patients with COPD exacerbation neither revealed any significant
      bronchodilating effect nor reduced duration of hospital stay. 

PMID- 25587313
TI  - Elevated Vancomycin Trough Concentration: Increased Efficacy and/or Toxicity?
AB  - Vancomycin susceptibility of methicillin-resistant Staphylococcus aureus has been
      changed over time and its average minimum inhibitory concentration increased from
      1.5 to 1.75 mg/L.A recently published guideline by the American Society of Health
      Pharmacist recommended a daily dose of 15-20 mg/Kg every 8 to 12 hours of
      vancomycin to achieve a trough concentration between 15-20 mg/L for treatment of
      severe infections. Medical records of 69 patients from infectious ward of Imam
      Khomeini hospital, with suspected or confirmed gram-positive infection who had at
      least one trough level of vancomycin, were evaluated regarding vancomycin
      therapeutic goal; efficacy and renal safety. Most of patients (60.6%) with severe
      infections did not achieve the recommended vancomycin trough level during
      treatment course. Time to normalization of the signs and symptoms of infection
      did not correlate with the patients' serum vancomycin trough levels. At the end
      of treatment course, there was no significant correlation between patients'
      creatinine clearance and vancomycin trough levels (P=0.32). However,
      patients'cratinine clearance showed a negatively significant correlation with
      trough level of vancomycin (P=0.01). Vancomycin induced nephrotoxicity was
      detected in 4.3% of the patients. These data showed that vancomycin trough level
      may not necessarily assure treatment success, and also it would not essentially
      predict the risk of vancomycin induced nephrotoxicity. However, more well
      designed studies with larger sample size needed for better clinical and practical
      judgment. 

PMID- 25587314
TI  - The Effect of Sumac (Rhus coriaria L.)Powder on Serum Glycemic Status, ApoB, ApoA
      I and Total Antioxidant Capacity in Type 2 Diabetic Patients.
AB  - Sumac (Rhus coriaria L.) is used as an herbal remedy in traditional medicine. The
      aim of this study was to determine the effects of sumac (R. coriaria) on serum
      glycemic status, apolipoprotein (apo) B, apoA-I and total antioxidant capacity
      (TAC) in type 2 diabetic patients. This double blind randomized controlled
      clinical trial was conducted on 41type 2 diabetic volunteers randomly assigned
      into 3g/day sumac powder (n=22) or placebo (n=19) groups over 3 months. Blood
      samples were collected before and after the intervention. Serum glucose and HbA1c
      were measured using enzymatic and turbidimetric inhibition immunoassay methods,
      respectively. ApoB, apoA-I and TAC were determined using turbidimetric
      immunoassay and spectrophotometric methods, respectively. There were significant
      decreases in serum glucose and HbA1c and also apoB levels at the end of study
      compared with initial values (P< 0.0001, P= 0.002 and P< 0.0001,respectively).
      Also, there was a significant difference in HbA1c and TAC levels between placebo
      and sumac groups at the end of study (P< 0.05).In sumac group, there were
      significant increase in apoA-I and TAC(P< 0.0001) compared with initial values.
      The mean of differences of serum glucose, HbA1c, apoB, apoA-I, apoB/apoA-I ratio
      and TAC between groups were significant (P< 0.05). In conclusion, these results
      showed the favorite effect of sumac consumption on serum glycemic status, apoB,
      apoA-I and TAC levels in in type 2 diabetic patients. 

PMID- 25587315
TI  - Effects of Inhalation of Lavender Essential Oil on Open-heart Surgery Pain.
AB  - This study evaluated the effects of inhalation of lavender essential oil on the
      pain of open-heart surgery. The main complaint of patients after open-heart
      surgery is chest pain. Due to the side effects of opioids, it is important to use
      a non-invasive way to effectively relieve pain including aromatherapy with
      analgesics. This study was a clinical single-blind trial and was conducted on 40
      patients who had open-heart surgery in the cardiac ICU of 2 Hospitals of Tehran
      University of Medical Sciences, 2012. Criteria included: full consciousness,
      spontaneous breathing ability and not using synthetic opioids within 2 hours
      before extubation. After extubation, the patients were asked to mark the
      intensity of their pain using the visual analogue scale. Then, a cotton swab
      which was impregnated with 2 drops of lavender essential oil 2% was placed in
      their oxygen mask, and they got breath for 10 minutes. 30 minutes after
      aromatherapy, they were asked to re-mark their pain intensity. The level of
      patient's pain before and after aroma therapy were compared. The pain mean level
      before and after inhaling lavender essential oil was 5.60 (SD = 2.262) and 4.98
      (SD = 2.293), respectively (p-value>0.05). Therefore, there is no significant
      difference and the result of study proves that lavender essential oil inhalation
      has no effect on reducing the pain of open-heart surgery. 

PMID- 25587317
TI  - The Effects of Extending of Co-planarity in a Series of Structurally Relative
      Polypyridyl Palladium(II) Complexes on DNA-binding and Cytotoxicity Properties.
AB  - In depth interaction studies between calf thymus deoxyribonucleic acid (CT-DNA)
      and a series of four structurally relative palladium(II) complexes
      [Pd(en)(HB)](NO3)2 (a-d), where en is ethylenediamine and heterocyclic base (HB)
      is 2,2'-bipyridine (bpy, a); 1,10-phenanthroline (phen, b); dipyridoquinoxaline
      (dpq, c) and dipyridophenazine (dppz, d) (Figure 1), were performed. These
      studies have been investigated by utilizing the electronic absorption
      spectroscopy, fluorescence spectra and ethidium bromide (EBr) displacement and
      gel filtration techniques. a-d complexes cooperatively bind and denature the DNA
      at low concentrations. Their concentration at midpoint of transition, L1/2,
      follows the order a >> b > c > d. Also the g, the number of binding sites per
      1000 nucleotides, follows the order a >> b ~ c > d. EBr and Scatchard experiments
      for a-d complexes suggest efficient intercalative binding affinity to CT-DNA
      giving the order: d > c > b > a. Several binding and thermodynamic parameters are
      also described. The biological activity of these cationic and water soluble
      palladium complexes were tested against chronic myelogenous leukemia cell line,
      K562. b, c and d complexes show cytotoxic concentration (Cc50) values much lower
      than cisplatin. 

PMID- 25587318
TI  - Effect of Dietary Ethanolic Extract of Lavandula officinalis on Serum Lipids
      Profile in Rats.
AB  - Antioxidants are effective in prevention and treatment of cardiovascular
      diseases. Lavandula officinalis possesses antioxidant activity, therefore, in
      this study; the effects of Lavandula officinalis extract were investigated on
      serum lipids levels of rats. Experimental mature male Wistar rats were treated
      with 100, 200 or 400 mg/Kg/day of lavender ethanolic extract or distilled water
      for 25 days via gastric gavage (n=8 each group). At the end of 25(th) day, the
      serum cholesterol, triglyceride, HDL, LDL and VLDL levels, as well as atherogenic
      indices were determined in rats' serum. The ethanolic extract of lavender
      decreased serum cholesterol, triglyceride, LDL and VLDL levels in 100 mg/Kg group
      (p=0.03, p=0.001, p=0.001, p=0.001, respectively). Serum HDL level increased in
      100 mg/Kg/day group (p=0.01). Lavender extract decreased LDL/HDL level at doses
      of 100 and 200 mg/Kg/day (p=0.001, p=0.001, respectively). The TG/HDL levels
      decreased in experimental groups with doses of 100 and 200 mg/Kg/day (p=0.001,
      p=0.001, respectively). Lavandula officinalis extract exerts hypolipidemic effect
      in rats and might be beneficial in hyperlipidemic patients. 

PMID- 25587316
TI  - Cytoprotective Effects of Hydrophilic and Lipophilic Extracts of Pistacia vera
      against Oxidative Versus Carbonyl Stress in Rat Hepatocytes.
AB  - This study was conducted to evaluate the cytoprotection of various extracts and
      bioactive compounds found in Pistacia vera againts cytotoxicity, ROS formation,
      lipid peroxidation, protein carbonylation, mitochondrial and lysosomal membrane
      damages in cell toxicity models of diabetes related carbonyl (glyoxal) and
      oxidative stress (hydroperoxide). Methanol, water and ethyl acetate were used to
      prepare crude pistachios extracts, which were then used to screen for in-vitro
      cytoprotection of freshly isolated rat hepatocytes against these toxins. The
      order of protection by Pistacia vera extracts against both hydroperoxide induced
      oxidative stress (ROS formation) and glyoxal induced protein carbonylation was:
      pistachio methanolic extract >pistachio water extract, gallic acid, catechin>
      alpha-tochoferol and pistachio ethyl acetate extract. Finally due to higher
      protection achieved by methanolic extract even compared to sole pretreatment of
      gallic acid, catechin or alpha-tochoferol, we suggest that cytoprotection depends
      on the variety of polar and non-polar compounds found in methanolic extract, it
      is likely that multiple cytoprotective mechanisms are acting against oxidative
      and carbonyl induced cytotoxicity. To our knowledge, we are the first to report
      the cytoprotective activity of Pistacia vera extracts against oxidative and
      carbonyl stress seen in type 2 diabetes hepatocytes model. 

PMID- 25587319
TI  - Role of Fructose as a Potent Antiarrhythmic and Anti-infarct agent in Isolated
      Rat Heart.
AB  - In the current study, effects of acute short term administration of fructose on
      cardiac arrhythmias and myocardial infarction size following ischemia/reperfusion
      were investigated in isolated rat heart. The hearts were subjected to 30 min zero
      flow global ischemia followed by 120 min reperfusion. In the control group, the
      hearts were perfused by normal drug free Krebs-Henseleit (K/H) solution
      throughout the experiments, while in the treated groups (2-4), they were perfused
      with fructose containing K/H solution at 12, 24 and 48 mM concentrations during
      stabilization and reperfusion time, respectively. Cardiac arrhythmias were
      determined based on the Lambeth conventions and the infarct size was measured by
      computerized planimetry. Myocardial infarction size was 22 +/- 3% in the control
      group, however administration of fructose (12, 24 and 48 mM) reduced it to 15 +/-
      3 (P<0.05), 7+/-2 (P<0.001) and 4 +/- 2% (P<0.001), respectively. A direct linear
      correlation between fructose concentrations and infarction size reduction was
      observed (R(2)=0.970). In addition, total number of ventricular ectopic beats
      were significantly decreased by all used concentrations of fructose (P<0.01 for
      group 2, P<0.001 for groups 3 and 4, respectively). Fructose also produced
      significant decrease in the number, incidence and duration of ventricular
      tachycardia compared to the control (P<0.05). The data showed that acute short
      term administration of fructose can protect isolated rat heart against
      ischemia/reperfusion injuries as reduction of infarct size and cardiac
      arrhythmias. Alterations in glycogen storage and/or glycolytic efficiency may
      probably involve in these cardioprotective effects. Also it is possible that
      fructose can act as a pharmacological preconditioning agent. 

PMID- 25587320
TI  - Antihyperglycemic and Antihyperlipidemic Effects of Fruit Aqueous Extract of
      Berberis integerrima Bge. in Streptozotocin-induced Diabetic Rats.
AB  - Use of medicinal plants for attenuation of hyperglycemia and restoration of
      lipids disorder to normal level is clinically very important. The aim of present
      study was to evaluate the effects of Berberis integerrima Bge. fruit aqueous
      extract (BIFAE) on blood glucose and lipid profile in streptozotocin (STZ) -
      induced diabetic rats. The STZ-induced diabetic rats were treated by fruit
      aqueous extract of Berberis integerrima Bge. at doses (250 and 500 mg/Kg bw) and
      glibenclamide (0.6 mg/Kg bw) for 42 days by gavage. Blood glucose levels and body
      weights of rats were measured on weeks 0, 2, 4 and 6. Total lipid levels were
      determined in normal and STZ-induced diabetic rats after administration of the
      BIFAE and glibenclamide for 42 days. STZ-induced diabetic rats showed a
      significant (P<0.001) increases in the levels of blood glucose, triglycerides
      (TG), total cholesterol (TC), low density lipoprotein LDL-cholesterol (LDL-C)
      while body weight and high density lipoprotein HDL-cholesterolan (HDL-C) were
      significantly(P<0.001) decreased compared to normal rats. Daily administration of
      BIFAE did not possess the hypoglycemic and hypolipidaemic activity in STZ-
      diabetic rats during 6-week treatment period. Results indicate the usage of BIFAE
      in traditional medicine for the treatment of diabetes may need more
      investigation. 

PMID- 25587321
TI  - Anethole, a Medicinal Plant Compound, Decreases the Production of Pro
      Inflammatory TNF-alpha and IL-1beta in a Rat Model of LPS-Induced Periodontitis.
AB  - Periodontitis (PD) is known to be one of most prevalent worldwide chronic
      inflammatory diseases. There are several treatments including antibiotics for PD;
      however, since drug resistance is an increasing problem, new drugs particularly
      derived from plants with fewer side effects are required. The effects of trans
      anethole on IL-1 beta and TNF-alpha level in a rat model of PD were investigated
      and compared to ketoprofen. Eschericia coli lipopolysaccharide (LPS, 30 ug) was
      injected bilaterally into the palatal gingiva (3 uL/site) between the upper first
      and second molars every two days for 10 days in anesthetized rats. Administration
      of either trans-anethole (10 or 50 mg/Kg, i.p.) or ketoprofen (10 mg/Kg, i.p.)
      was started 20 minute before LPS injection and continued for 10 days. Then, IL
      1beta and TNF-alpha levels were measured in blood samples by ELISA at day 0
      (control) and at day 10. Anethole at both concentrations significantly suppressed
      IL-1beta and TNF-alpha production when compared to LPS-treated rats. The
      suppressive effects of anethole on LPS-induced pro-inflammatory cytokines were
      almost similar as seen with ketoprofen. In conclusion, the present results
      suggest that anethole may have a potent inhibitory effect on PD through
      suppression of pro-inflammatory molecules; therefore it could be a novel
      therapeutic strategy for PD. 

PMID- 25587322
TI  - Econazole Nitrate Induces Apoptosis in MCF-7 Cells via Mitochondrial and Caspase
      Pathways.
AB  - Econazole nitrate (EN), a synthetic compound, is now in use as a routine
      antifungal drug. EN was shown to have antitumor effect, the tumor cell killing
      mechanisms, however, remain unclear. In this research, the apoptosis-inducing
      effect of EN on MCF-7 cells was investigated. The results showed that EN
      inhibited the proliferation of MCF-7 cells in a time- and dose-dependent manner
      by MTT method and colony forming assay. MCF-7 cells treated with EN showed
      typical characteristics of apoptosis including the morphological changes and DNA
      fragmentation. Meanwhile, the loss of mitochondrial membrane potential was showed
      by flow cytometry. In addition, western blot analysis showed that EN resulted in
      the decrease expression of procaspase-3, procaspase-9 and bcl-2. In conclusion,
      these findings suggest that EN may be an effective way for treating human breast
      cancer. The anti-tumor mechanisms of EN might involve mitochondrial and caspase
      pathways. 

PMID- 25587323
TI  - Anti-tumor Activity of Ferulago angulata Boiss. Extract in Gastric Cancer Cell
      Line via Induction of Apoptosis.
AB  - Ferulago angulata Boiss. known in Iran as Chavir, has some bioactive compounds
      having antioxidant activity. Because of its antioxidant activities, it sounded
      Chavir extract can be a good candidate for finding chemopreventive agents having
      inductive apoptosis properties on cancer cells. In this study, the cytotoxic
      effects and proapoptotic activities of Chavir's leaf and flower extracts were
      investigated on human adenocarcinoma gastric cell line (AGS). The ferric reducing
      antioxidant power (FRAP) assay was used to determine antioxidant activity of the
      extract. Cytotoxic effects of the extract were performed by trypan blue and
      neutral red assays. For apoptosis detection, we used Annexin V staining, flow
      cytometry and DNA fragmentation assays. The FRAP assay results showed that
      antioxidant activity of leaf extract was higher than flower extract. Cytotoxicity
      and apoptosis-inducing activity of flower and leaf extracts changed coordinately,
      indicating the cytotoxicity of chavir extracts is due probably to induce
      apoptosis. Our results revealed that the cytotoxic effects of F. angulate Boiss.
      extracts on AGS cell line is close to some other plant extracts such as Rhus
      verniciflua Stokes (RVS) and Scutellaria litwinowii. This is the first study on
      cytotoxic and apoptosis-inducing effects of chavir leaf and flower extracts
      against AGS cell line. The Further investigation can be identification of the
      agent(s) by which these effects is observed. 

PMID- 25587324
TI  - Buckwheat Rutin Inhibits AngII-induced Cardiomyocyte Hypertrophy via Blockade of
      CaN-dependent Signal Pathway.
AB  - Buckwheat rutin has been found to be able to inhibit angiotensin II (AngII) -
      induced hypertrophy in cultured neonatal rat cardiomyocytes, but the mechanism
      remains uncertain. In this study, myocardial hypertrophy model was made by adding
      AngII to the medium of cardiac myocytes of neonatal rats; meanwhile, different
      concentrations of buckwheat rutin were applied to observe their effects.
      Intracellular Ca(2+) level was detected by Hitachi - 850 fluorospectrophotometer,
      calcineurin (CaN) activity was measured by colorimetric method, the expression of
      CaN protein was observed with immunocytochemistry, and the proto - oncogene c -
      fos mRNA expression was assessed with reverse transcription polymerase chain
      reaction (RT - PCR). Compared with control group, AngII could greatly stimulate
      the increase of intracellular Ca(2+) level, the activities and protein expression
      of cardiomyocytes CaN, and the expression of proto - oncogene c - fos mRNA in
      cultured neonatal rat cardiomyocytes, which could be effectively decreased by
      buckwheat rutin. Our results demonstrated that buckwheat rutin exhibited
      inhibitory effect on AngII - induced hypertrophy in cultured neonatal rat
      cardiomyocytes via Ca(2+) antagonism action thus block the CaN - dependent signal
      pathway. 

PMID- 25587325
TI  - Evaluation of a Novel Herbal Immunomodulator Drug (IMOD) in Treatment of
      Experimental Canine Visceral leishmaniasis.
AB  - Toxicity and drug resistance against pentavalent antimonials, medications of
      choice in treatment of leishmaniasis for more than 5 decades, have become
      important subjects globally. This study was a randomized, open labeled trial that
      was designed to determine efficacy and safety of IMOD as a novel herbal
      immunomodulator drug for treatment of canine visceral leishmaniasis (CVL). Twenty
      healthy mongrel dogs were infected with Iranian strain of L. Infantum amastigotes
      and randomly divided to 5 groups with four animals for each included on: I:
      negative control (non-infected) II: Glucantime(r) III: Glucantime(r) plus IMOD
      (immune-chemotherapy) IV: IMOD and V: positive control (non-treated). Physical
      examination, hematological, biochemical, serological, parasitological,
      pathological and imaging evaluations were performed pre-/post- interventions
      every month for 3 months. Comparing with control groups (I&V), immune
      chemotherapy group (Glucantime(r) plus IMOD) showed significantly higher efficacy
      in resolving the clinical signs and hematobiochemistry factors. Based on our
      results, using IMOD in combination with meglumine antimoniate (Glucantime(r)) has
      significantly improved CVL than the latter drug alone. So, it seems this new
      herbal medicine is useful as adjuvant therapy for canine visceral leishmaniasis. 

PMID- 25587326
TI  - Protective Effects of Lindera coreana on UVB-induced Oxidative Stress in Human
      HaCaT Keratinocytes.
AB  - The present study was designed to investigate the protective effect of ethanol
      extracts from Lindera coreana leaves (LCE) on UVB-induced oxidative stress in
      HaCaT keratinocytes. The HaCaT cells were pretreated with LCE for 24 h and then
      exposed to UVB (20 mJ/cm(2)) for 2 h. UVB significantly decreased the cell
      viability (p<0.05). LCE did not exhibit significantly cytotoxic effects and
      increased the viability of the HaCaT cells in a concentration-dependent manner.
      To further investigate the protective effects of LCE on UVB-induced oxidative
      stress in HaCaT cells, the cellular levels of reactive oxygen species (ROS),
      lipid peroxidation and endogenous antioxidant enzymes, including catalase (CAT),
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), were analyzed.
      LCE decreased the intracellular levels of ROS and lipid peroxidation and
      increased the activity of antioxidant enzymes. These results suggest that LCE
      exerted cytoprotective activity against UVB-induced oxidative stress in HaCaT
      cells through the inhibition of lipid peroxidation, reduction of ROS levels and
      stimulation of antioxidant enzymes activities. In addition, LCE also decreased
      the TNF-alpha, IL-1beta and IL-6 levels in UVB-irradiated HaCaT cells. 

PMID- 25587328
TI  - Mcl-1 is up regulated by prenylated coumarin, umbelliprenin in jurkat cells.
AB  - Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the
      western world and exists as subtypes with very different clinical courses.
      Myeloid cell leukemia 1 (Mcl-1) is one member of Bcl-2 family proteins that has
      been shown to be expressed in various tissues and malignant cells, including CLL,
      where its expression is significantly associated with a failure to achieve
      complete remission following cytotoxic therapy. Induction of apoptosis by
      prenylated coumarin, umbelliprenin, in Jurkat cells was previously shown. We
      examined whether umbelliprenin can down-regulate Mcl-1 gene and protein in Jurkat
      cells. In this regard cells were incubated by umbelliprenin, and then down-
      regulation of Mcl-1 gene was studied by Real Time PCR method. Moreover, down
      regulation of Mcl-1 protein was studied by western blot analysis. We showed that,
      expression of Mcl-1 mRNA was increased from 1 hour to 3 hours incubation, but
      this increase has a scale down pattern. Moreover umbelliprenin could inhibit Mcl
      1 protein. In conclusion umbelliprenin treatment modulates Mcl-1 expression at
      both the transcriptional and posttranslational levels.

PMID- 25587327
TI  - Use of artificial neural networks to examine parameters affecting the
      immobilization of streptokinase in chitosan.
AB  - Streptokinase is a potent fibrinolytic agent which is widely used in treatment of
      deep vein thrombosis (DVT), pulmonary embolism (PE) and acute myocardial
      infarction (MI). Major limitation of this enzyme is its short biological half
      life in the blood stream. Our previous report showed that complexing
      streptokinase with chitosan could be a solution to overcome this limitation. The
      aim of this research was to establish an artificial neural networks (ANNs) model
      for identifying main factors influencing the loading efficiency of streptokinase,
      as an essential parameter determining efficacy of the enzyme. Three variables,
      namely, chitosan concentration, buffer pH and enzyme concentration were
      considered as input values and the loading efficiency was used as output.
      Subsequently, the experimental data were modeled and the model was validated
      against a set of unseen data. The developed model indicated chitosan
      concentration as probably the most important factor, having reverse effect on the
      loading efficiency. 

PMID- 25587329
TI  - Celecoxib Up Regulates the Expression of Drug Efflux Transporter ABCG2 in Breast
      Cancer Cell Lines.
AB  - Elevated expression of the drug efflux transporter ABCG2 seems to correlate with
      multidrug resistance of cancer cells. Specific COX-2 inhibitor celecoxib has been
      shown to enhance the sensitivity of cancer cells to anticancer drugs. To clarify
      whether ABCG2 inhibition is involved in the sensitizing effect of celecoxib, we
      investigated whether the expression of ABCG2 in breast cancer cell lines, could
      be modulated by celecoxib. The expression of the multidrug resistant gene (ABCG2)
      at mRNA and protein level was detected by real-time quantitative reverse
      transcription-polymerase chain reaction and flow cytometry analysis,
      respectively. Among three human breast cancer cell lines ABCG2 and COX-2 were
      highly expressed in MCF7-MX and MDA-MB-231 cells, respectively. The COX-2
      inhibitor celecoxib up-regulated the expression of ABCG2 mRNA in MCF-7 and MCF7
      MX cells, which was accompanied by increased ABCG2 protein expression. While
      celecoxib was able to block the 12-O-tetradecanoylphorbol-13-acetate (TPA)
      mediated increase in COX-2 expression in MDA-MB-231 cells, it increased the
      expression of ABCG2 up to 4.27 times to the control level at mRNA level and with
      less intensity at protein level. Our findings provide evidence that celecoxib up
      regulates ABCG2 expression in human breast cancer cells and proposed that ABCG2
      is not involved in chemosensitizing effects of celecoxib. 

PMID- 25587330
TI  - Structural characterisation of a polysaccharide from radix ranunculus ternati.
AB  - A water soluble polysaccharide, HB-1, with a molecular weight of 23,930, was
      isolated from radix Ranunculi ternati. by hot water extraction, ethanol
      precipitation, deproteination,ultrafiltration and gel-filtration column
      chromatography. Its sugar composition was determined by GLC as Glc, Ara, and Gal
      in a molar ration of 16.071: 2.722: 1. And the absolute configuration of Glc was
      identified as D. Smith degradation and methylation reaction showed the proportion
      of -(1)Glc (A) was about 16%, -(1)Glc(4)- (B) about 62%, (C) about 14%, and 
      (1)Gal(6)- (D) about 8%. The repetitive unit was likely composed of 3 As, 3 Cs,
      13 Bs and 1 D. Together with the average molecular weight, it was predictable
      that HB-1 consisted of about seven of the repetitive unit. The inhibition
      activity of HB-1 on human glioma cell line SF188 was also measured, only to find
      it inactive. 

PMID- 25587331
TI  - Antioxidant, Metal Chelating, Anti-glucosidase Activities and Phytochemical
      Analysis of Selected Tropical Medicinal Plants.
AB  - The purpose of this investigation was to determine the antioxidant potentials and
      anti-glucosidase activities of six tropical medicinal plants. The levels of
      phenolic constituents in these medicinal plants were also quantified and
      compared. Antioxidation potentials were determined colorimetrically for
      scavenging activities against DPPH and NO radicals. Metal chelating assay was
      based on the measurement of iron-ferrozine absorbance at 562 nm. Anti-diabetic
      potentials were measured by using alpha-glucosidase as target enzyme. Medicinal
      plants' total phenolic, total flavonoid and hydroxycinnamic acid contents were
      determined using spectrophotometric methods, by comparison to standard plots
      prepared using gallic acid, quercetin and caffeic acid standards, respectively.
      Radical scavenging and metal chelating activities were detected in all medicinal
      plants, in concentration-dependent manners. Among the six plants tested, C.
      nutans, C. formosana and H. diffusa were found to possess alpha-glucosidase
      inhibitory activities. Spectrophotometric analysis indicated that the total
      phenolic, total flavonoid and hydroxycinnamic acid contents ranged from 12.13
      21.39 mg GAE per g of dry sample, 1.83-9.86 mg QE per g of dry sample, and 0.91
      2.74 mg CAE per g of dry sample, respectively. Our results suggested that C.
      nutans and C. formosana could potentially be used for the isolation of potent
      antioxidants and anti-diabetic compounds. To the best of our knowledge, this
      study represents the first time that C. nutans (Acanthaceae family) was reported
      in literature with glucosidase inhibition activity. 

PMID- 25587332
TI  - Chemical Composition and Antibacterial Activity of Essential Oil of Cosmos
      bipinnatus Cav. Leaves from South Africa.
AB  - The chemical composition of essential oils isolated from the leaves of Cosmos
      bipinnatus and its antibacterial activity were analyzed by GC-MS and microbroth
      dilution assay respectively. The essential oil extracted from this plant was
      predominantly composed of monoterpenes (69.62%) and sesquiterpenes (22.73%). The
      antibacterial assay showed that the oil had significant inhibitory effects
      against both Gram-negative and Gram-positive bacteria isolates. The MIC of Gram
      positive strains ranged between 0.16 and 0.31 mg/mL while those of Gram-negative
      bacteria ranged between 0.31 and 0.63 mg/mL. The Gram-positive bacteria were more
      susceptible to the essential oil than the Gram-negative bacteria. Most of the
      major components of this oil in other plants have been reported for antimicrobial
      activities. The antibacterial activity can be attributed to effects of the
      combination of several components of the oil. The results indicate that the C.
      bipinnatus might be exploited as natural antibacterial agent and have application
      in the treatment of several infectious diseases caused by these bacteria. Since
      this species is endemic to the eastern Free State, the plant could be collected
      during its bloom and used efficiently in the management of bacterial infections
      in South Africa. 

PMID- 25587333
TI  - Procerenone: a Fatty Acid Triterpenoid from the Fruit Pericarp of Omphalocarpum
      procerum (Sapotaceae).
AB  - Phytochemical investigation of a dichloromethane-methanol (1:1) extract of the
      fruit pericarp of Omphalocarpum procerum which exhibited antiplasmodial activity
      during preliminary screening led to the isolation of the new fatty ester
      triterpenoid 3beta-hexadecanoyloxy-28-hydroxyolean-12-en-11-one (1), together
      with five known compounds 2-6. The structure of the new compound as well as those
      of the known compounds was established by means of spectroscopic methods and by
      comparison with previously reported data. Compounds 1- 4 were evaluated in-vitro
      for their cytotoxicity against L6 cell lines and antiprotozoal activities against
      Plasmodium falciparum, Leishmania donovani, Trypanosoma brucei rhodesiense and
      Trypanosoma cruzi (species responsible for human malaria, visceral leishmaniasis,
      African trypanosomiasis and Chagas disease, respectively). The tested compounds
      showed weak to moderate antiprotozoal activity and, no significant effect was
      detected regarding their cytotoxic potency. 

PMID- 25587334
TI  - Improvement of Lidocaine Local Anesthetic Action Using Lallemantia royleana Seed
      Mucilage as an Excipient.
AB  - Lallemantia royleana (Balangu) is a well known Iranian medicinal plant that its
      seed mucilage has many applications in modern pharmacology. Plant mucilage
      traditionally was used as a gel supplement, and natural matrix for sustained
      release of drugs. But it seems that these compounds are not a simple additive and
      also have many undiscovered pharmacological properties. In this research, the
      anesthetic action of gel prepared from Balangu mucilage alone and its mixture
      with lidocaine hydrochloride are compared with the effect of commercial 2%
      lidocaine gel by rat tail flick test. Mucilage of Balangu seed alone showed
      analgesic effect. Duration and potency of anesthesia induced by gel containing
      mucilage alone (0.01 g/mL) were identical to commercial 2% lidocaine gel. But,
      local anesthetic potency and duration of gel made from 2% lidocaine-mucilage gel
      mixture was significantly higher than commercial 2% lidocaine gel. The gel
      prepared from mucilage causes a good analgesia with unknown mechanism. Besides,
      mixture of Balangu mucilage prepared gel with lidocaine improves lidocaine
      anesthesia. The increase in potency of lidocaine action results from mucilage
      dermal penetration enhancing effects; and longer anesthetic duration of this
      mixture are related to the capability of mucilage based gel for sustained drug
      release. 

PMID- 25587335
TI  - Determination of some B Vitamins in Sour Cherry Juice Using Dispersive Liquid
      liquid Microextraction Followed by High-performance Liquid Chromatography.
AB  - Dispersive liquid-liquid microextraction method (DLLME) combined with high
      performance liquid chromatography-ultraviolet detection (HPLC-UV) was used to
      determine thiamine (B1), nicotinamide (B3) and pyridoxine (B6) in sour cherry
      juice. This method was rapid, simple and sensitive. Separation was accomplished
      using a C18 column. The optimum chromatographic conditions were found to be:
      mobile phase consisted of 8% methanol and 92% aqueous phase (1% (V/V) acetic acid
      water solution); flow rate, 0.7 mL/min; detection wavelength, 260 nm and pH, 3.3.
      The extraction efficiency of thiamine, nicotinamide and pyridoxine was influenced
      by factors such as: additional salt effect, the kind and volume of disperser and
      extraction solvents. In this research, the limit of detection (LOD) and
      quantification (LOQ) were 0.9 and 3 ng/mL for thiamine, 1.5 and 5 ng/mL for
      nicotinamide, 0.9 and 3 ng/mL for pyridoxine. The relative standard deviations
      (RSDs) were less than 2.87% (n=3). An appropriate linear behavior over the
      observed concentration range was obtained with the value of R2>0.996 for the
      target vitamins. This method was successfully applied to the sour cherry juice
      samples. Sour cherry var. Gise (Prunus cerasus var. Gise), which was used in this
      research, was a local variety of the sour cherry with large stone, double
      flowers, double fruits, dark red skin and dark red juice. This variety was
      identified in high altitude areas of Isfahan province after five years of study,
      since 2005, by Agricultural and Natural Resources Research Center of Isfahan. 

PMID- 25587336
TI  - In-vitro Callus Induction and Rosmarinic Acid Quantification in Callus Culture of
      Satureja khuzistanica Jamzad (Lamiaceae).
AB  - In the present study, an efficient protocol has been developed for callus
      induction and production of RA in callus culture of Satureja khuzistanica for the
      first time. In-vitro callus induction was achieved from young shoot tip explants
      cultured on MS and B5 media supplemented with different concentrations of IBA
      (0.1, 1.0, 2.0 and 5.0 mgL(-1)) solely or in combination with cytokinins BAP and
      KIN (1.0, 2.0 and 5.0 mgL(-1)). B5 medium supplemented with 1.0 mgL(-1) IBA plus
      5.0 mgL(-1) BAP and MS medium fortified with 2.0 mgL(-1) IBA and 2.0 mgL(-1) BAP
      were the most favorable media for callus formation with the highest induction
      rate (96%). Maximum growth index (2.89 and 2.63) and maximum callus biomass (2.34
      and 2.33 g fresh weight) were obtained from the callus cultured on B5 medium
      supplemented with 1.0 mgL(-1) IBA plus 5.0 mgL(-1) BAP and MS medium fortified
      with 1.0 mgL(-1) IBA plus 1.0 mgL(-1) KIN, respectively. Determination and
      quantification of RA in cultured calli were performed by HPLC UV/MS analysis.
      Calli induced from the plant and maintained on supplements of IBA and BAP in the
      absence of light produced RA 7.5% based on dry weight (DW). No differentiation
      was observed in any callus during the course of this study. 

PMID- 25587337
TI  - Knowledge, Attitude and Practice of Pharmacists regarding Dietary Supplements : A
      Community Pharmacy- based survey in Tehran.
AB  - The present study aimed to evaluate pharmacy practice regarding dietary
      supplements in Tehran (I.R. Iran). So, the factors affecting on pharmacists'
      practice including their knowledge, attitude, and some underlying factors were
      evaluated. This is an observational knowledge; attitude and practice (KAP) study.
      The unit of analysis include pharmacies practice located in Tehran. The data was
      collected in 2013 via an anonymous, self-administered; postal questionnaire
      consisted of demographic information, knowledge (subjective and objective
      questions), attitude, and practice evaluation part. Descriptive and inferential
      statistics were performed using SPSS. This study showed that although the
      knowledge has a significant effect on attitude and practice, the attention should
      be paid on other underlying factors such as experience, pharmacy ownership
      situation and academic degree which might have positive impact on pharmacists'
      practice. According to this study, although many underlying factors such as
      experience, university and pharmacy ownership have impact on pharmacy practice
      regarding dietary supplements, the most attention should paid to knowledge as the
      main factor and more attention should be paid to training on dietary supplement
      could be recommended. 

PMID- 25587338
TI  - Effects of Oils and Essential Oils from Seeds of Zanthoxylum schinifolium against
      Foodborne Viral Surrogates.
AB  - Human noroviruses are the most frequent cause of foodborne viral disease and are
      responsible for the vast majority of nonbacterial gastroenteritis. However, no
      specific therapies are available for the efficient control or prevention of
      foodborne viral disease. Here, we determined the antiviral activities of oils
      from seeds of Zanthoxylum schinifolium (ZSO) against foodborne viral surrogates,
      feline calicivirus-F9 (FCV-F9), and murine norovirus-1 (MNV-1), using plaque
      assay. Time-of-addition experiments were designed to determine the antiviral
      mechanism of action of ZSO against the surrogates. Maximal antiviral effect was
      observed upon pretreatment of FCV-F9 or MNV-1 with ZSO, which comprised oleic
      acid, linoleic acid, palmitic acid, and linolenic acid as the major fatty acids.
      FCV-F9 was more sensitive to ZSO than MNV-1, and the 50% effective concentration
      of ZSO against pretreatment of FCV-F9 was 0.0007%. However, essential oils from
      Z. schinifolium (ZSE), which comprised 42% estragole, showed no inhibitory
      effects against FCV-F9 and MNV-1. These results suggest that the inhibitory
      activities of ZSO were exerted by direct interaction of FCV-F9 or MNV-1 virion
      with ZSO, which may be a food material candidate for control of foodborne viral
      disease. 

PMID- 25587339
TI  - Chemical Assessment and Antimicrobial and Antioxidant Activities of Endophytic
      Fungi Extracts Isolated from Costus spiralis (Jacq.) Roscoe (Costaceae).
AB  - Costus spiralis (Costaceae) is a species native to the Amazon region and is used
      in traditional medicine. The endophytic fungi used in this study were obtained
      from leaves of this plant. 13 strains were selected to obtain hydroethanolic
      extracts and were submitted to hydroalcoholic extraction and evaluated for
      antioxidant activity by DPPH (2,2-difenil-1-picrilhidrazil) and FRAP (ferric
      reducing antioxidant power), and all of the fungi had positive results. The
      antimicrobial action of crude extracts had a good range of activities. All
      extracts had inhibitory activities against the yeasts of Candida albicans and C.
      parapsilosis, with 125 to 500 MUg/mL MIC. Eight extracts had antimicrobial
      activities against Bacillus subtilis (MIC from 62.4 to 125 MUg/mL), 5 against
      Pseudomonas aeruginosa (MIC from 125 to 500 MUg/mL), 2 against Salmonella
      enterica (MIC from 125 to 62.5 MUg/mL), and 2 against Enterococcus faecalis (MIC
      from 500 to 125 MUg/mL). The presence of secondary metabolites, including
      coumarins, was observed during chemical evaluation by thin layer chromatography.
      Total phenol content was estimated, and a strong positive correlation to
      antioxidant activity was observed, according to its Pearson coefficient. This is
      the first report of the bioactive potential of endophytic fungi isolated from the
      Costaceae family in Brazilian ecosystems. 

PMID- 25587340
TI  - Shenfu injection for intradialytic hypotension: a systematic review and meta
      analysis.
AB  - Objective. To evaluate the effectiveness and safety of Shenfu injection (SFI) for
      intradialytic hypotension (IDH). Methods. A systematic review of data sources
      published as of April 2014 was conducted. These included the Cochrane Central
      Register of Controlled Trials (2014 issue 4), Pubmed, Embase, CBM, CNKI, VIP, and
      Wangfang Data. Randomized controlled trials (RCTs) involving SFI for treatment
      and prevention of IDH were identified. Two researchers independently selected
      articles, extracted data, assessed quality, and cross checked the results. Revman
      5.2 was used to analyze the results. Results. Eight RCTs were included. The meta
      analysis indicated that compared with conventional therapies alone, SFI could
      elevate systolic blood pressure (SBP), increase the clinical effective rate,
      decrease the incidence of hypotension, increase serum albumin (ALB) levels, and
      reduce C-reactive protein (CRP) levels without serious adverse effects. GRADE
      Quality of Evidence. the quality of SBP, the effective rate, ALB, and CRP were
      low, and hypotension incidence and DBP were very low. Conclusions. SFI is more
      effective than conventional therapies for prevention and treatment of IDH.
      However, a clinical recommendation is not warranted due to the small number of
      studies included and low methodology quality. Multi-center and high-quality RCTs
      with large sample sizes are needed to provide stronger evidence. 

PMID- 25587341
TI  - Use of angong niuhuang in treating central nervous system diseases and related
      research.
AB  - In Chinese medicine-based therapeutics, Angong Niuhuang pill (ANP) is one of the
      three most effective formulas for febrile diseases, and it is also used to treat
      other diseases. This paper reviews current knowledge regarding the clinical and
      pharmacological effects of ANP for treating different central nervous system
      (CNS) diseases to confirm its validity and efficacy. These diseases are like
      centric fever, coma, stroke, and viral encephalitis. This review reveals that
      various diseases could be treated using the same agent, which is one of the most
      important principles of traditional Chinese medicine (TCM). According to the
      "Same Treatment for Different Diseases" principle, ANP might be efficacious in
      other CNS diseases. 

PMID- 25587342
TI  - Antidepressant-like effects of cordycepin in a mice model of chronic
      unpredictable mild stress.
AB  - Cordycepin (3'-deoxyadenosine), a major bioactive component isolated from
      Cordyceps militaris, has multiple pharmacological activities. This study is
      attempted to investigate whether cordycepin (COR) possesses beneficial effects on
      chronic unpredictable mild stress- (CUMS-) induced behavioral deficits
      (depression-like behaviors) and explore the possible mechanisms. ICR mice were
      subjected to chronic unpredictable mild stress for 42 consecutive days. Then, COR
      and fluoxetine (FLU, positive control drug) were administered for 21 consecutive
      days at the last three weeks of CUMS procedure. The classical behavioral tests,
      open field test (OFT), sucrose preference test (SPT), tail suspension test (TST),
      and forced swimming test (FST), were applied to evaluate the antidepressant
      effects of COR. Then the serotonin (5-HT) and noradrenaline (NE) concentrations
      in hippocampal were evaluated by HPLC; tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6) in hippocampal were evaluated, and the proteins of TNF
      alpha, IL-6, NF-kappaBP65 5-HT2A receptor (5-HT2AR), and brain-derived
      neurotrophic factor (BDNF) in hippocampal were evaluated by Western blot. Our
      results indicated that 6 weeks of CUMS exposure induced significant depression
      like behavior, with low 5-HT and NE levels, high TNF-alpha and IL-6 in brain and
      high hippocampal TNF-alpha, IL-6, P-NF-kappaBP65, and 5-HT2AR levels, and low
      BDNF expression levels. Whereas, chronic COR (20, 40 mg/kg) treatments reversed
      the behavioral deficiency induced by CUMS exposure, treatment with COR normalized
      the change of TNF-alpha, IL-6, 5-HT, and NE levels, which demonstrated that COR
      could partially restore CUMS-induced 5-HT receptor impairments and inflammation.
      Besides, hippocampal BDNF expressions were also upregulated after COR treatments.
      In conclusion, COR remarkably improved depression-like behavior in CUMS mice and
      its antidepressant activity is mediated, at least in part, by the upregulating
      BDNF and downregulating 5-HT2AR levels and inflammation in hippocampus. 

PMID- 25587343
TI  - Coptis chinensis and Myrobalan (Terminalia chebula) Can Synergistically Inhibit
      Inflammatory Response In Vitro and In Vivo.
AB  - Objectives. To investigate the anti-inflammatory effect of Coptis chinensis plus
      myrobalan (CM) in vitro and in vivo. Methods. The inflammation in mouse
      peritoneal macrophages was induced by lipopolysaccharide (LPS). Animal models
      were established by using ear swelling and paw edema of mouse induced by xylene
      and formaldehyde, respectively. In vitro, cytotoxicity, the phagocytosis of
      macrophages, the levels of nitric oxide (NO), induced nitric oxide synthase
      (iNOS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in cell
      supernatant were detected. In vivo, swelling rate and edema inhibitory rate of
      ear and paw were observed using CM-treated mice. Results. At 150-18.75 MUg.mL(
      1), CM had no cytotoxicity and could significantly promote the growth and the
      phagocytosis of macrophages and inhibit the overproduction of NO, iNOS, TNF
      alpha, and IL-6 in macrophages induced by LPS. In vivo, pretreatment with CM, the
      ear swelling, and paw edema of mice could be significantly inhibited in a dose
      dependent manner, and the antiedema effect of CM at high dose was better than
      dexamethasone. Conclusion. Our results demonstrated that Coptis chinensis and
      myrobalan possessed synergistically anti-inflammatory activities in vitro and in
      vivo, which indicated that CM had therapeutic potential for the prevention and
      treatment of inflammation-mediated diseases. 

PMID- 25587345
TI  - Improving research on the efficacy, effectiveness, and harms of traditional
      chinese medicine.

PMID- 25587344
TI  - The effect of massage therapy on autonomic activity in critically ill children.
AB  - Objectives. Our main objective was to describe the effect of foot and hand (F&H)
      massage on the autonomic nervous system (ANS) activity in children hospitalized
      in a pediatric intensive care unit (PICU); the secondary objectives were to
      assess the relationship between ANS function and the clinical severity and to
      explore the effects of repeated massage sessions on the ANS. Methods. Design was
      a descriptive experimental study. Intervention was single or six session(s) of
      F&H massage. ANS function was assessed through the frequency-domain analysis of
      heart rate variability. Main metrics included high and low frequency power (HF
      and LF), HF + LF, and LF/HF ratio. Results. Eighteen children participated in the
      study. A strong Spearman's correlation (rho = -0.77) was observed between HF + LF
      and clinical severity. During massage, the parasympathetic activity (measured by
      HF) increased significantly from baseline (P = 0.04) with a mean percentage
      increase of 75% (95% CI: 20%~130%). LF increased by 56% (95% CI: 20%~92%) (P =
      0.026). Repeated sessions were associated with a persistent effect on HF and LF
      which peaked at the second session and remained stable thereafter. Conclusions.
      HF + LF is positively correlated with clinical severity. F&H massage can improve
      the ANS activity and the effect persists when repeated sessions are offered. 

PMID- 25587346
TI  - Phenolic Profiling and Evaluation of Contraceptive Effect of the Ethanolic
      Extract of Salsola imbricata Forssk. in Male Albino Rats.
AB  - Reported researches dealing with either composition or bioactivity of Salsola
      imbricata are limited. This study was conducted aiming to investigate the
      phenolic composition of the plant and evaluate its efficacy as male
      contraceptive. Polyphenols, namely, phenolic acids and flavonoids, were
      qualitatively and quantitatively analysed by RP-HPLC in the hydrolysed methanol
      extract using two different wavelengths, 280 and 330 nm. The efficiency of
      different solvents in extracting the plant phenolics was assessed via
      spectrophotometric determination of the total phenolic and flavonoid contents.
      Acute toxicity study was carried out on the ethanolic extract to ascertain its
      safety prior to biological evaluation. The contraceptive effect was assessed, in
      male rats, by oral administration of the extract at two doses (250 and 500 mg/kg
      b. wt.), over a period of 65 days. HPLC analyses allowed the identification and
      quantification of a total of 13 and 8 components in the hydrolysed-methanol
      extract; the overall phenolic composition was dominated by quercitrin (12.692%)
      followed by coumaric acid (4.251%). Prolonged oral administration of the
      ethanolic extract caused slight reduction in the testis weight only. A
      significant decrease in the sperm count was observed (P < 0.01) in the two
      treated groups while significant decrease in the epididymal sperm motility was
      only observed in the high dose group. Morphological abnormalities were observed
      in sperms of treated animals. No distinct change in serum FSH, LH, and
      testosterone concentration was recorded. The histopathological findings supported
      to a high extent these results. The male contraceptive activity of Salsola
      imbricata could be ascribed to its phenolic components, especially quercitrin. 

PMID- 25587349
TI  - Automatic segmentation of anatomical structures from CT scans of thorax for RTP.
AB  - Modern radiotherapy techniques are vulnerable to delineation inaccuracies owing
      to the steep dose gradient around the target. In this aspect, accurate contouring
      comprises an indispensable part of optimal radiation treatment planning (RTP). We
      suggest a fully automated method to segment the lungs, trachea/main bronchi, and
      spinal canal accurately from computed tomography (CT) scans of patients with lung
      cancer to use for RTP. For this purpose, we developed a new algorithm for
      inclusion of excluded pathological areas into the segmented lungs and a modified
      version of the fuzzy segmentation by morphological reconstruction for spinal
      canal segmentation and implemented some image processing algorithms along with
      them. To assess the accuracy, we performed two comparisons between the
      automatically obtained results and the results obtained manually by an expert.
      The average volume overlap ratio values range between 94.30 +/- 3.93% and 99.11
      +/- 0.26% on the two different datasets. We obtained the average symmetric
      surface distance values between the ranges of 0.28 +/- 0.21 mm and 0.89 +/- 0.32
      mm by using the same datasets. Our method provides favorable results in the
      segmentation of CT scans of patients with lung cancer and can avoid heavy
      computational load and might offer expedited segmentation that can be used in
      RTP.

PMID- 25587348
TI  - Human atrial cell models to analyse haemodialysis-related effects on cardiac
      electrophysiology: work in progress.
AB  - During haemodialysis (HD) sessions, patients undergo alterations in the
      extracellular environment, mostly concerning plasma electrolyte concentrations,
      pH, and volume, together with a modification of sympathovagal balance. All these
      changes affect cardiac electrophysiology, possibly leading to an increased
      arrhythmic risk. Computational modeling may help to investigate the impact of HD
      related changes on atrial electrophysiology. However, many different human atrial
      action potential (AP) models are currently available, all validated only with the
      standard electrolyte concentrations used in experiments. Therefore, they may
      respond in different ways to the same environmental changes. After an overview on
      how the computational approach has been used in the past to investigate the
      effect of HD therapy on cardiac electrophysiology, the aim of this work has been
      to assess the current state of the art in human atrial AP models, with respect to
      the HD context. All the published human atrial AP models have been considered and
      tested for electrolytes, volume changes, and different acetylcholine
      concentrations. Most of them proved to be reliable for single modifications, but
      all of them showed some drawbacks. Therefore, there is room for a new human
      atrial AP model, hopefully able to physiologically reproduce all the HD-related
      effects. At the moment, work is still in progress in this specific field. 

PMID- 25587347
TI  - A review of hepatoprotective plants used in saudi traditional medicine.
AB  - Liver disease is one of the major causes of morbidity and mortality across the
      world. According to WHO estimates, about 500 million people are living with
      chronic hepatitis infections resulting in the death of over one million people
      annually. Medicinal plants serve as a vital source of potentially useful new
      compounds for the development of effective therapy to combat liver problems.
      Moreover herbal products have the advantage of better affordability and
      acceptability, better compatibility with the human body, and minimal side effects
      and is easier to store. In this review attempt has been made to summarize the
      scientific data published on hepatoprotective plants used in Saudi Arabian
      traditional medicine. The information includes medicinal uses of the plants,
      distribution in Saudi Arabia, ethnopharmacological profile, possible mechanism of
      action, chemical constituents, and toxicity data. Comprehensive scientific
      studies on safety and efficacy of these plants can revitalise the treatment of
      liver diseases. 

PMID- 25587350
TI  - Mathematical analysis of non-Newtonian blood flow in stenosis narrow arteries.
AB  - The flow of blood in narrow arteries with bell-shaped mild stenosis is
      investigated that treats blood as non-Newtonian fluid by using the K-L model.
      When skin friction and resistance of blood flow are normalized with respect to
      non-Newtonian blood in normal artery, the results present the effect of stenosis
      length. When skin friction and resistance of blood flow are normalized with
      respect to Newtonian blood in stenosis artery, the results present the effect of
      non-Newtonian blood. The effect of stenosis length and effect of non-Newtonian
      fluid on skin friction are consistent with the Casson model in which the skin
      friction increases with the increase of either stenosis length or the yield
      stress but the skin friction decreases with the increase of plasma viscosity
      coefficient. The effect of stenosis length and effect of non-Newtonian fluid on
      resistance of blood flow are contradictory. The resistance of blood flow (when
      normalized by non-Newtonian blood in normal artery) increases when either the
      plasma viscosity coefficient or the yield stress increases, but it decreases with
      the increase of stenosis length. The resistance of blood flow (when normalized by
      Newtonian blood in stenosis artery) decreases when either the plasma viscosity
      coefficient or the yield stress increases, but it decreases with the increase of
      stenosis length.

PMID- 25587351
TI  - Mathematical modeling of radiofrequency ablation for varicose veins.
AB  - We present a three-dimensional mathematical model for the study of radiofrequency
      ablation (RFA) with blood flow for varicose vein. The model designed to analyze
      temperature distribution heated by radiofrequency energy and cooled by blood flow
      includes a cylindrically symmetric blood vessel with a homogeneous vein wall. The
      simulated blood velocity conditions are U = 0, 1, 2.5, 5, 10, 20, and 40 mm/s.
      The lower the blood velocity, the higher the temperature in the vein wall and the
      greater the tissue damage. The region that is influenced by temperature in the
      case of the stagnant flow occupies approximately 28.5% of the whole geometry,
      while the region that is influenced by temperature in the case of continuously
      moving electrode against the flow direction is about 50%. The generated RF energy
      induces a temperature rise of the blood in the lumen and leads to an occlusion of
      the blood vessel. The result of the study demonstrated that higher blood velocity
      led to smaller thermal region and lower ablation efficiency. Since the peak
      temperature along the venous wall depends on the blood velocity and pullback
      velocity, the temperature distribution in the model influences ablation
      efficiency. The vein wall absorbs more energy in the low pullback velocity than
      in the high one.

PMID- 25587352
TI  - Important CT findings for prediction of severe appendicitis: involvement of
      retroperitoneal space.
AB  - BACKGROUND: Determination of the severity of appendicitis and differentiation
      between complicated and uncomplicated appendicitis are clinically important.
      Severe appendicitis frequently affects extraperitoneal spaces. We have
      investigated CT findings of retroperitoneal space (RPS) in patients with
      appendicitis to create a model for identification of complicated appendicitis.
      METHOD: CT images of 223 patients with pathologically proven appendicitis were
      reviewed. The total number of the segments in RPS where inflammatory changes were
      located (RPS count) was obtained as well as appendiceal diameter,
      appendicolithiasis, WBC count, and CRP level. Data were analyzed to identify
      factors indicating complicated appendicitis. Univariate analysis was conducted to
      identify statistically significant variables. A multivariable logistic regression
      analysis was performed in order to find independent predictors of complicated
      appendicitis. RESULTS: Patients with complicated appendicitis were more likely to
      have higher RPS count (P < 0.001), appendicolithiasis (P = 0.002), higher CRP
      level (P < 0.001), and greater appendix diameter (P < 0.001) than patients with
      uncomplicated appendicitis. Statistical analysis showed RPS count was the most
      helpful predictor of complicated appendicitis. CONCLUSION: Radiologists and
      surgeons should be aware of the importance of CT findings in RPS when treating
      patients with appendicitis. Complicated appendicitis can be predicted by RPS
      count, diameter of the appendix, appendicolithiasis, and CRP level.

PMID- 25587354
TI  - Assessment of cyclooxygenase-1 and 2 gene expression levels in chronic autoimmune
      thyroiditis, papillary thyroid carcinoma and nontoxic nodular goitre.
AB  - INTRODUCTION: The cyclooxygenases are a group of enzymes catalyzing the formation
      of prostaglandins from arachidonic acid. Cyclooxygenase-1 (COX-1) is a
      constitutive form, thought to be a "housekeeping gene", with constant levels of
      expression in most tissues. COX-1 expression in the thyroid gland, except for
      medullary thyroid carcinoma, has not been a subject of much interest.
      Cyclooxygenase-2 (COX-2) can be expressed in response to various stimuli, such as
      mitogens, hormones, cytokines, growth factors. The product of COX-2 activity has
      been implicated in carcinogenesis. Recent studies have shown that up-regulation
      of COX-2 is associated with numerous neoplasms. Hereby, we present a study
      analysing COX-1 and COX-2 expression in papillary thyroid carcinoma (PTC),
      Hashimoto thyroiditis (HT) and nontoxic nodular goitre (NNG) in fine needle
      aspiration biopsy (FNAB) washouts and in postoperative tissue. MATERIAL AND
      METHODS: Cytological specimens from 120 patients (105 females and 15 males) have
      been studied, including patients with HT, PTC and NNG. Moreover, we have examined
      postoperative tissue specimens from 51 patients with PTC and NNG. The methods of
      molecular analysis have included extraction of total RNA from FNAB cytological
      material and postoperative tissues, spectrophotometric assessment of the RNA
      purity, cDNA synthesis in reverse transcription reaction and an analysis of genes
      expression data by real-time PCR. RESULTS: The performed analysis has revealed
      statistically significant higher expression level of the COX-2 gene in PTC group,
      in comparison with HT and NNG groups (in both cytological and postoperative
      material). In PTC patients, COX-2 gene expression levels in the material obtained
      by FNAB were similar to those in the postoperative thyroid tissue. No
      correlations between COX-2 gene expression level and TNM staging in PTC samples
      have been observed. There were no correlations between COX-2 expression and anti
      TPO antibodies level, or patient's sex or age in the studied groups. Also, there
      were no correlations of COX-1 gene expression level among PTC, HT and NNG groups.
      CONCLUSIONS: Our results suggest that COX-2 gene does not participate in the
      mechanisms involved in molecular association of HT with PTC. However, in case of
      PTC itself, it may play some role in neoplastic transformation.

PMID- 25587353
TI  - Correlates of psychological functioning of homeless youth in Accra, Ghana: a
      cross-sectional study.
AB  - BACKGROUND: Research on homeless youth has shown that this population is at high
      risk for various mental health problems. Previous studies conducted among
      homeless young adults in Ghana have focused primarily on economic, social and
      cultural causes of homelessness, their engagement in risky sexual behaviours and
      the prevalence of STI including HIV/AIDS. We are therefore not fully informed of
      the prevalence of psychological symptoms and their associated factors. The aim of
      the study was to determine the association between psychological functioning and
      social and health risk behaviours among a sample of homeless youth in Ghana.
      METHODS: A cross-sectional survey of a convenience sample of 227 (122 male and
      105 female) homeless youth was conducted in Ghana in 2013. An interviewer
      administered questionnaire was used to collect data due to low level of literacy
      among the study population. Pearson-moment correlation coefficient (r) and
      multiple standard regression models were fitted to analyse the data. RESULTS:
      Approximately 87% of the participants in this study exhibited moderate to severe
      psychosocial symptoms. Specifically, emotional, conduct, hyperactivity and peer
      relationship problems among the participants were 69%, 74%, 54% and 89%
      respectively. Overall psychosocial functioning was predicted by stigma (self
      stigma and experienced stigma), violent behaviours and suicidal ideation.
      Substance use and perceived resilience were significantly associated with
      emotional problems. CONCLUSION: There is a need for holistic interventions to
      help improve the psychological and social functioning of homeless youth. Such
      programmes should strengthen socio-emotional coping strategies in street youth as
      well as address contextual risk factors such as stigma and discrimination by the
      public.

PMID- 25587355
TI  - HP1beta-dependent recruitment of UBF1 to irradiated chromatin occurs
      simultaneously with CPDs.
AB  - BACKGROUND: The repair of spontaneous and induced DNA lesions is a multistep
      process. Depending on the type of injury, damaged DNA is recognized by many
      proteins specifically involved in distinct DNA repair pathways. RESULTS: We
      analyzed the DNA-damage response after ultraviolet A (UVA) and gamma irradiation
      of mouse embryonic fibroblasts and focused on upstream binding factor 1 (UBF1), a
      key protein in the regulation of ribosomal gene transcription. We found that
      UBF1, but not nucleolar proteins RPA194, TCOF, or fibrillarin, was recruited to
      UVA-irradiated chromatin concurrently with an increase in heterochromatin protein
      1beta (HP1beta) level. Moreover, Forster Resonance Energy Transfer (FRET)
      confirmed interaction between UBF1 and HP1beta that was dependent on a functional
      chromo shadow domain of HP1beta. Thus, overexpression of HP1beta with a deleted
      chromo shadow domain had a dominant-negative effect on UBF1 recruitment to UVA
      damaged chromatin. Transcription factor UBF1 also interacted directly with DNA
      inside the nucleolus but no interaction of UBF1 and DNA was confirmed outside the
      nucleolus, where UBF1 recruitment to DNA lesions appeared simultaneously with
      cyclobutane pyrimidine dimers; this occurrence was cell-cycle-independent.
      CONCLUSIONS: We propose that the simultaneous presence and interaction of UBF1
      and HP1beta at DNA lesions is activated by the presence of cyclobutane pyrimidine
      dimers and mediated by the chromo shadow domain of HP1beta. This might have
      functional significance for nucleotide excision repair.

PMID- 25587356
TI  - Next generation sequencing analysis of nine Corynebacterium ulcerans isolates
      reveals zoonotic transmission and a novel putative diphtheria toxin-encoding
      pathogenicity island.
AB  - BACKGROUND: Toxigenic Corynebacterium ulcerans can cause a diphtheria-like
      illness in humans and have been found in domestic animals, which were suspected
      to serve as reservoirs for a zoonotic transmission. Additionally, toxigenic C.
      ulcerans were reported to take over the leading role in causing diphtheria in the
      last years in many industrialized countries. METHODS: To gain deeper insights
      into the tox gene locus and to understand the transmission pathway in detail, we
      analyzed nine isolates derived from human patients and their domestic animals
      applying next generation sequencing and comparative genomics. RESULTS: We provide
      molecular evidence for zoonotic transmission of C. ulcerans in four cases and
      demonstrate the superior resolution of next generation sequencing compared to
      multi-locus sequence typing for epidemiologic research. Additionally, we provide
      evidence that the virulence of C. ulcerans can change rapidly by acquisition of
      novel virulence genes. This mechanism is exemplified by an isolate which acquired
      a prophage not present in the corresponding isolate from the domestic animal.
      This prophage contains a putative novel virulence factor, which shares high
      identity with the RhuM virulence factor from Salmonella enterica but which is
      unknown in Corynebacteria so far. Furthermore, we identified a putative
      pathogenicity island for C. ulcerans bearing a diphtheria toxin gene. CONCLUSION:
      The novel putative diphtheria toxin pathogenicity island could provide a new and
      alternative pathway for Corynebacteria to acquire a functional diphtheria toxin
      encoding gene by horizontal gene transfer, distinct from the previously well
      characterized phage infection model. The novel transmission pathway might explain
      the unexpectedly high number of toxigenic C. ulcerans.

PMID- 25587357
TI  - A multi-gene signature predicts outcome in patients with pancreatic ductal
      adenocarcinoma.
AB  - BACKGROUND: Improved usage of the repertoires of pancreatic ductal adenocarcinoma
      (PDAC) profiles is crucially needed to guide the development of predictive and
      prognostic tools that could inform the selection of treatment options. METHODS:
      Using publicly available mRNA abundance datasets, we performed a large
      retrospective meta-analysis on 466 PDAC patients to discover prognostic gene
      signatures. These signatures were trained on two clinical cohorts (n = 70), and
      validated on four independent clinical cohorts (n = 246). Further validation of
      the identified gene signature was performed using quantitative real-time RT-PCR.
      RESULTS: We identified 225 candidate prognostic genes. Using these, a 36-gene
      signature was discovered and validated on fully independent clinical cohorts
      (hazard ratio (HR) = 2.06, 95% confidence interval (CI) = 1.51 to 2.81, P = 3.62
      * 10(-6), n = 246). This signature serves as a good alternative prognostic
      stratification marker compared to tumour grade (HR = 2.05, 95% CI = 1.45 to 2.88,
      P = 3.18 * 10(-5)) and tumour node metastasis (TNM) stage (HR = 1.13, 95% CI =
      0.66 to 1.94, P = 0.67). Upon multivariate analysis with adjustment for TNM stage
      and tumour grade, the 36-gene signature remained an independent prognostic
      predictor of clinical outcome (HR = 2.21, 95% CI = 1.17 to 4.16, P = 0.01).
      Univariate assessment revealed higher expression of ITGA5, SEMA3A, KIF4A, IL20RB,
      SLC20A1, CDC45, PXN, SSX3 and TMEM26 was correlated with shorter survival while
      B3GNT1, NOSTRIN and CADPS down-regulation was associated with poor outcome.
      CONCLUSIONS: Our 36-gene classifier is able to prognosticate PDAC independent of
      patient cohort and microarray platforms. Further work on the functional roles,
      downstream events and interactions of the signature genes is likely to reveal
      true molecular candidates for PDAC therapeutics.

PMID- 25587358
TI  - Complex host genetics influence the microbiome in inflammatory bowel disease.
AB  - BACKGROUND: Human genetics and host-associated microbial communities have been
      associated independently with a wide range of chronic diseases. One of the
      strongest associations in each case is inflammatory bowel disease (IBD), but
      disease risk cannot be explained fully by either factor individually. Recent
      findings point to interactions between host genetics and microbial exposures as
      important contributors to disease risk in IBD. These include evidence of the
      partial heritability of the gut microbiota and the conferral of gut mucosal
      inflammation by microbiome transplant even when the dysbiosis was initially
      genetically derived. Although there have been several tests for association of
      individual genetic loci with bacterial taxa, there has been no direct comparison
      of complex genome-microbiome associations in large cohorts of patients with an
      immunity-related disease. METHODS: We obtained 16S ribosomal RNA (rRNA) gene
      sequences from intestinal biopsies as well as host genotype via Immunochip in
      three independent cohorts totaling 474 individuals. We tested for correlation
      between relative abundance of bacterial taxa and number of minor alleles at known
      IBD risk loci, including fine mapping of multiple risk alleles in the Nucleotide
      binding oligomerization domain-containing protein 2 (NOD2) gene exon. We
      identified host polymorphisms whose associations with bacterial taxa were
      conserved across two or more cohorts, and we tested related genes for enrichment
      of host functional pathways. RESULTS: We identified and confirmed in two cohorts
      a significant association between NOD2 risk allele count and increased relative
      abundance of Enterobacteriaceae, with directionality of the effect conserved in
      the third cohort. Forty-eight additional IBD-related SNPs have directionality of
      their associations with bacterial taxa significantly conserved across two or
      three cohorts, implicating genes enriched for regulation of innate immune
      response, the JAK-STAT cascade, and other immunity-related pathways. CONCLUSIONS:
      These results suggest complex interactions between genetically altered host
      functional pathways and the structure of the microbiome. Our findings demonstrate
      the ability to uncover novel associations from paired genome-microbiome data, and
      they suggest a complex link between host genetics and microbial dysbiosis in
      subjects with IBD across independent cohorts.

PMID- 25587359
TI  - Assessment of patient-derived tumour xenografts (PDXs) as a discovery tool for
      cancer epigenomics.
AB  - BACKGROUND: The use of tumour xenografts is a well-established research tool in
      cancer genomics but has not yet been comprehensively evaluated for cancer
      epigenomics. METHODS: In this study, we assessed the suitability of patient
      derived tumour xenografts (PDXs) for methylome analysis using Infinium 450 K
      Beadchips and MeDIP-seq. RESULTS: Controlled for confounding host (mouse)
      sequences, comparison of primary PDXs and matching patient tumours in a rare
      (osteosarcoma) and common (colon) cancer revealed that an average 2.7% of the
      assayed CpG sites undergo major (Deltabeta >= 0.51) methylation changes in a
      cancer-specific manner as a result of the xenografting procedure. No significant
      subsequent methylation changes were observed after a second round of xenografting
      between primary and secondary PDXs. Based on computational simulation using
      publically available methylation data, we additionally show that future studies
      comparing two groups of PDXs should use 15 or more samples in each group to
      minimise the impact of xenografting-associated changes in methylation on
      comparison results. CONCLUSIONS: Our results from rare and common cancers
      indicate that PDXs are a suitable discovery tool for cancer epigenomics and we
      provide guidance on how to overcome the observed limitations.

PMID- 25587360
TI  - Visceral adiposity index score indicated the severity of coronary heart disease
      in Chinese adults.
AB  - BACKGROUND: Visceral adiposity contributes to cardiometabolic risk, and visceral
      adiposity index (VAI) had significant correlation with visceral adiposity. We
      aimed to explore whether VAI was associated with cardiac structure and function
      and assess the impact of the cut-off points of VAI defining visceral adipose
      dysfunction (VAD) on the severity of coronary heart disease (CHD). METHODS: A
      total of 95 patients with CHD were divided into Control (nondiabetic CHD
      patients) and DM group (diabetic CHD patients). Then the two groups were
      respectively divided into VAD absent and VAD groups. Clinical, echocardiographic
      and coronary artery angiographic indexes were acquired to examine in relation to
      VAI. RESULTS: A significant increasing trend among the four groups of patients
      (Control + VAD absent, Control +VAD, DM + VAD absent and DM +VAD groups) were
      observed for waist circumference (WC), body mass index (BMI), systolic blood
      pressure (SBP), glucose, VAI and Gensini score (P<0.05 for all). The following
      variables were associated with VAI: total cholesterol, nonesterified fatty acid,
      Waist-Hip ratio and SBP. VAI was independently associated with Gensini score.
      CONCLUSIONS: The extent of CHD was more severe in diabetes, and VAI as a simple
      indicator of visceral adipose mass was strongly associated with the severity of
      CHD. The cut-off points of VAI used for defining VAD were more useful in diabetic
      CHD patients in identifying the severity of CHD.

PMID- 25587361
TI  - Malformation and plastic surgery in childhood.
AB  - Malformations of the head and neck show a huge variety of clinical symptoms with
      functional and esthetic consequences. Often times its rehabilitation requires
      multi-staged and multi-disciplinary procedures and concepts. These must consider
      eating, speech, mimic expression, hearing and "esthetics" or at least
      "normality". A survey of the most common head and neck malformations and their
      treatment options are presented here. 

PMID- 25587363
TI  - Pediatric radiology in oto-rhino-laryngology.
AB  - Head and neck diseases in children and adolescents present special diagnostic and
      differential diagnostic challenges to ENT surgeons as well as to radiologists.
      Both disciplines have to adapt the latest radiological and interventional
      technologies to the needs of the pediatric patient in order to enable a minimally
      invasive but successful diagnostic procedure. High quality sonography by an
      experienced examiner is often the only imaging technique that is necessary in
      children and adolescents. Radiographs are rarely indicated in pediatric head and
      neck diseases. MRI, compared to computed tomography, has the advantage of absent
      radiation exposure. Additionally, due to current advances in high resolution
      techniques to delineate very small details or in visualization of different
      tissue characteristics, it has become an integral part of pre- and postoperative
      imaging. However, children should not be denied an adequate diagnostic procedure
      even if it includes sedation, intervention, or exposure to radiation. The
      responsible use of the diagnostic options under consideration of the therapeutic
      consequences is essential. It is most likely to be successful in a close
      interdisciplinary cooperation of pediatric ENT specialists and radiologists as
      well as pediatric anesthesiologists in selected cases. Although benign diseases
      predominate in children and adolescents, the possibility of malignancy has to be
      considered in cases of atypical clinical and radiological findings. In many of
      these young patients, the outcome and the probability of survival are directly
      associated with the initial diagnostic and therapeutic strategies, which should
      therefore be in accordance with the current guidelines of pediatric oncology
      therapy studies. Our collection of clinical cases consists of representative
      examples of useful diagnostic approaches in common and age specific diagnoses as
      well as in rare diseases and malformations. It shows the significance of a
      special knowledge in embryology and normal postnatal development for the
      differentiation of normal variants from pathological findings. Only in
      considering the results of imaging studies in their clinical context, it is
      possible to succeed in detecting a syndrome behind a single malformation or
      adequately caring for patients with a chronic disease such as cystic fibrosis. 

PMID- 25587362
TI  - Extracranial vascular malformations (hemangiomas and vascular malformations) in
      children and adolescents - diagnosis, clinic, and therapy.
AB  - The field of extracranial vascular anomalies is considered as special focus of
      pediatric otolaryngology and it has shown a rapid development during the last
      years. The reason for this interest is finally also due to the global acceptance
      of the classification introduced by the ISSVA (International Society for the
      Study of Vascular Anomalies). Hemangiomas are the most frequently observed
      vascular tumors. Today the systemic propranolol therapy is mostly used for
      therapy of hemangiomas requiring treatment. Increasingly, the topical application
      of beta blocker is discussed while the benefit in the head and neck seems to be
      limited. Vascular malformations are classified according to the morphology of the
      affected part of the vascular system in arterial, venous, arterio-venous,
      lymphatic, capillary, and combined vascular malformations. Conventional surgery,
      sclerosing therapy, and laser treatment are invasive options for the treatment of
      lymphatic malformations. The options for the treatment of venous malformations
      could be significantly improved during the last years. In this context, the use
      of Nd:YAG laser, the conservative treatment of the localized disseminated
      intravascular coagulation with low-molecular weight heparin, the re-discovery of
      bleomycin as effective sclerosing agent, and the improvement of alcohol-based
      embolization agents must be mentioned. Today the treatment with dye laser is the
      preferred therapy for capillary malformations and it is superior to other
      therapeutic options as for example photodynamic therapy. Arterio-venous
      malformations as representatives for high-flow lesions are the high-risk lesions.
      Frequently they are compared to malignant head and neck tumors, in particular
      when a curative treatment can no longer be assured because of diffuse or
      multifocal extent and when the disease shows a progressive course. The combined
      treatment of embolization and surgical resection and if necessary consecutive
      defect reconstruction have turned out to be appropriate for arterio-venous
      malformations. Incurable findings are still a major challenge. Despite the
      introduction of antiangiogenetic drugs in oncology, the medicamentous therapeutic
      approach could not be established for arterio-venous malformations up to now. 

PMID- 25587364
TI  - Anesthesia for ORL surgery in children.
AB  - ORL procedures are the most common operations in children - an optimal anesthetic
      management provides an uncomplicated, safe perioperative process with as little
      discomfort for the child as possible. Children at risk must already be identified
      preoperatively: the combination of ORL surgery, airway susceptibility and age
      below 3 years can increase the risk of perioperative respiratory adverse events.
      Postoperatively, it is important to prevent complications such as pain and PONV
      by dedicated prevention and treatment strategies, as well as to recognize and
      treat respiratory or circulatory complications competently. Interdisciplinary
      guidelines and agreements as well as the overall competence of the team have the
      potential to improve patient safety and outcome in children. 

PMID- 25587365
TI  - Hearing impairment and language delay in infants: Diagnostics and genetics.
AB  - This overview study provides information on important phoniatric and audiological
      aspects of early childhood hearing and language development with the aim of
      presenting diagnostic and therapeutic approaches. The article first addresses the
      universal newborn hearing screening that has been implemented in Germany for all
      infants since January 2009. The process of newborn hearing screening from the
      maternity ward to confirmation diagnostics is presented in accordance with a
      decision by the Federal Joint Committee (G-BA). The second topic is pediatric
      audiology diagnostics. Following confirmation of a permanent early childhood
      hearing disorder, the search for the cause plays an important role. Hereditary
      hearing disorders and intrauterine cytomegalovirus (CMV) infection, probably the
      most common cause of an acquired hearing disorder, are discussed and compared
      with the most common temporary hearing disorder, otitis media with effusion,
      which in some cases is severe enough to be relevant for hearing and language
      development and therefore requires treatment. The third topic covered in this
      article is speech and language development in the first 3 years of life, which is
      known today to be crucial for later language development and learning to read and
      write. There is a short overview and introduction to modern terminology, followed
      by the abnormalities and diagnostics of early speech and language development.
      Only some aspects of early hearing and language development are addressed here.
      Important areas such as the indication for a cochlear implant in the first year
      of life or because of unilateral deafness are not included due to their
      complexity. 

PMID- 25587366
TI  - Salivary gland diseases in children.
AB  - Salivary gland diseases in children are rare, apart from viral-induced diseases.
      Nevertheless, it is essential for the otolaryngologist to recognize these
      uncommon findings in children and adolescents and to diagnose and initiate the
      proper treatment. The present work provides an overview of the entire spectrum of
      congenital and acquired diseases of the salivary glands in childhood and
      adolescence. The current literature was reviewed and the results discussed and
      summarized. Besides congenital diseases of the salivary glands in children, the
      main etiologies of viral and bacterial infections, autoimmune diseases and tumors
      of the salivary glands were considered. In addition to the known facts, new
      developments in diagnostics, imaging and therapy, including sialendoscopy in
      obstructive diseases and chronic recurrent juvenile sialadenitis were taken into
      account. In addition, systemic causes of salivary gland swelling and the
      treatment of sialorrhoea were discussed. Although salivary gland diseases in
      children are usually included in the pathology of the adult, they differ in their
      incidence and some-times in their symptoms. Clinical diagnostics and especially
      the surgical treatment are influenced by a stringent indications and a less
      invasive strategy. Due to the rarity of tumors of the salivary glands in
      children, it is recommended to treat them in a specialized center with greater
      surgical experience. Altogether the knowledge of the differential diagnoses in
      salivary gland diseases in children is important for otolaryngologists, to
      indicate the proper therapeutic approach. 

PMID- 25587369
TI  - Pathologies of the larynx and trachea in childhood.
AB  - Pathologies in the larynx and trachea in the pediatric age can be characterized
      in 4 main groups: airway stenosis, acute infections, benign neoplasia and foreign
      body aspiration. In this review main diagnostic strategies and therapeutic
      options are presented. Laryngomalazia is the most frequent condition of
      supraglottic stenosis. The term supraglottoplasty summarizes all different
      techniques used for it's repair using an endoscopic approach. Glottic stenosis is
      rare in children. Usually a compromise between voice preservation and airway
      restoration has to be sought. Type of reconstruction and timing are varying
      considerably in individual cases, endoscopic approaches should be preferred.
      Subglottic stenosis remains the largest group in paediatric airway pathology,
      with cicatrial stenosis being predominant. Today, cricotracheal resection is the
      most successful treatment option, followed by the classical laryngotracheal
      reconstruction with autologous cartilage. In early infancy subglottic stenosis is
      particularly demanding. Endoscopic treatment is possible in selected patients,
      but open reconstruction is superior in more severe cases. Tracheostomy is not a
      safe airway in early infancy, it's indication should be strict. Foreign body
      aspiration needs to be managed according to a clear algorhythm. Recurrent
      respiratory papillomatosis should be treated with emphasis on function
      preservation. The role of adjuvant medication remains unclear. Infectious
      diseases can be managed conservatively by a pediatrician in the majority of
      cases. 

PMID- 25587368
TI  - Cervical lymph node diseases in children.
AB  - The lymph nodes are an essential part of the body's immune system and as such are
      affected in many infectious, autoimmune, metabolic and malignant diseases. The
      cervical lymph nodes are particularly important because they are the first
      drainage stations for key points of contact with the outside world
      (mouth/throat/nose/eyes/ears/respiratory system) - a critical aspect especially
      among children - and can represent an early clinical sign in their exposed
      position on a child's slim neck. Involvement of the lymph nodes in multiple
      conditions is accompanied by a correspondingly large number of available
      diagnostic procedures. In the interests of time, patient wellbeing and cost, a
      careful choice of these must be made to permit appropriate treatment. The basis
      of diagnostic decisions is a detailed anamnesis and clinical examination.
      Sonography also plays an important role in differential diagnosis of lymph node
      swelling in children and is useful in answering one of the critical diagnostic
      questions: is there a suspicion of malignancy? If so, full dissection of the most
      conspicuous lymph node may be necessary to obtain histological confirmation.
      Diagnosis and treatment of childhood cervical lymph node disorders present the
      attending pediatric and ENT physicians with some particular challenges. The
      spectrum of differential diagnoses and the varying degrees of clinical relevance 
      from banal infections to malignant diseases - demand a clear and considered
      approach to the child's individual clinical presentation. Such an approach is
      described in the following paper. 

PMID- 25587367
TI  - Tonsillitis and sore throat in children.
AB  - Surgery of the tonsils is still one of the most frequent procedures during
      childhood. Due to a series of fatal outcomes after hemorrhage in children in
      Austria in 2006, the standards and indications for tonsillectomy have slowly
      changed in Germany. However, no national guidelines exist and the frequency of
      tonsil surgery varies across the country. In some districts eight times more
      children were tonsillectomized than in others. A tonsillectomy in children under
      six years should only be done if the child suffers from recurrent acute
      bacterially tonsillitis. In all other cases (i.e. hyperplasia of the tonsils) the
      low risk partial tonsillectomy should be the first line therapy. Postoperative
      pain and the risk of hemorrhage are much lower in partial tonsillectomy
      (=tonsillotomy). No matter whether the tonsillotomy is done by laser,
      radiofrequency, shaver, coblation, bipolar scissor or Colorado needle, as long as
      the crypts are kept open and some tonsil tissue is left behind. Total
      extracapsular tonsillectomy is still indicated in severely affected children with
      recurrent infections of the tonsils, allergy to antibiotics, PFAPA syndrome
      (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) and
      peritonsillar abscess. With regard to the frequency and seriousness of the
      recurrent tonsillitis the indication for tonsillectomy in children is justified
      if 7 or more well-documented, clinically important, adequately treated episodes
      of throat infection occur in the preceding year, or 5 or more of such episodes
      occur in each of the 2 preceding years (according to the paradise criteria).
      Diagnosis of acute tonsillitis is clinical, but sometimes it is hard to
      distinguish viral from bacterial infections. Rapid antigen testing has a very low
      sensitivity in the diagnosis of bacterial tonsillitis and swabs are highly
      sensitive but take a long time. In all microbiological tests the treating
      physician has to keep in mind, that most of the bacterials, viruses and fungi
      belong to the healthy flora and do no harm. Ten percent of healthy children even
      bear strepptococcus pyogenes all the time in the tonsils with no clinical signs.
      In these children decolonization is not necessary. Therefore, microbiological
      screening tests in children without symptoms are senseless and do not justify an
      antibiotic treatment (which is sometimes postulated by the kindergartens). The
      acute tonsillitis should be treated with steroids (e.g. dexamethasone), NSAIDs
      (e.g. ibuprofene) and betalactam antibiotics (e.g. penicillin or cefuroxime).
      With respect to the symptom reduction and primary healing the short-term late
      generation antibiotic therapy (azithromycin, clarithromycin or cephalosporine for
      three to five days) is comparable to the long-term penicilline therapy. There is
      no difference in the course of healing, recurrence or microbiological resistance
      between the short-term penicilline therapy and the standard ten days therapy. On
      the other hand, only the ten days antibiotic therapy has proven to be effective
      in the prevention of rheumatic fever and glomerulonephritic diseases. The
      incidence of rheumatic heart disease is currently 0.5 per 100,000 children of
      school age. The main morbidity after tonsillectomy is pain and the late
      haemorrhage. Posttonsillectomy bleeding can occur till the whole wound is
      completely healed, which is normally after three weeks. Life-threatening
      haemorrhages occur often after smaller bleedings, which can spontaneously cease.
      That is why every haemorrhage, even the smallest, has to be treated properly and
      in ward. Patients and parents have to be informed about the correct behaviour in
      case of haemorrhage with a written consent before the surgery. The handout should
      contain important addresses, phone numbers and contact persons. Almost all cases
      of fatal outcome after tonsillectomy were due to false management of haemorrhage.
      Haemorrhage in small children can be especially life-threatening because of the
      lower blood volume and the danger of aspiration with asphyxia. A massive
      haemorrhage is an extreme challenge for every paramedic or emergency doctor
      because of the difficult airway management. Intubation is only possible with
      appropriate inflexible suction tubes. All different surgical techniques have the
      risk of haemorrhage and even the best surgeon will experience a postoperative
      haemorrhage. The lowest risk of haemorrhage is after cold dissection with
      ligature or suturing. All "hot" techniques with laser, radiofrequency, coblation,
      mono- or bipolar forceps have a higher risk of late haemorrhage. Children with a
      hereditary coagulopathy have a higher risk of haemorrhage. It is possible, that
      these children were not identified before surgery. Therefore it is recommended by
      the Society of paediatrics, anaesthesia and ENT, that a standardised
      questionnaire should be answered by the parents before tonsillectomy and
      adenoidectomy. This 17-point-checklist questionnaire is more sensitive and easier
      to perform than a screening with blood tests (e.g. INR and PTT). Unfortunately, a
      lot of surgeons still screen the children preoperatively by coagulative blood
      tests, although these tests are inappropriate and incapable of detecting the von
      Willebrand disease, which is the most frequent coagulopathy in Europe. The
      preoperative information about the surgery should be done with the child and the
      parents in a calm and objective atmosphere with a written consent. A copy of the
      consent with the signature of the surgeon and both custodial parents has to be
      handed out to the parents. 

PMID- 25587372
TI  - Making a hydrophoretic focuser tunable using a diaphragm.
AB  - Microfluidic diagnostic devices often require handling particles or cells with
      different sizes. In this investigation, a tunable hydrophoretic device was
      developed which consists of a polydimethylsiloxane (PDMS) slab with hydrophoretic
      channel, a PDMS diaphragm with pressure channel, and a glass slide. The height of
      the hydrophoretic channel can be tuned simply and reliably by deforming the
      elastomeric diaphragm with pressure applied on the pressure channel. This
      operation allows the device to have a large operating range where different
      particles and complex biological samples can be processed. The focusing
      performance of this device was tested using blood cells that varied in shape and
      size. The hydrophoretic channel had a large cross section which enabled a
      throughput capability for cell focusing of ~15 000 cells s(-1), which was more
      than the conventional hydrophoretic focusing and dielectrophoresis (DEP)-active
      hydrophoretic methods. This tunable hydrophoretic focuser can potentially be
      integrated into advanced lab-on-a-chip bioanalysis devices. 

PMID- 25587373
TI  - A large-area hemispherical perforated bead microarray for monitoring bead based
      aptamer and target protein interaction.
AB  - Herein, we present a large-area 3D hemispherical perforated microwell structure
      for a bead based bioassay. Such a unique microstructure enables us to perform the
      rapid and stable localization of the beads at the single bead level and the
      facile manipulation of the bead capture and retrieval with high speed and
      efficiency. The fabrication process mainly consisted of three steps: the convex
      micropatterned nickel (Ni) mold production from the concave micropatterned
      silicon (Si) wafer, hot embossing on the polymer matrix to generate the concave
      micropattened acrylate sheet, and reactive ion etching to make the bottom holes.
      The large-area hemispherical perforated micropatterned acrylate sheet was
      sandwiched between two polydimethylsiloxane (PDMS) microchannel layers. The bead
      solution was injected and recovered in the top PDMS microchannel, while the
      bottom PDMS microchannel was connected with control lines to exert the
      hydrodynamic force in order to alter the flow direction of the bead solution for
      the bead capture and release operation. The streptavidin-coated microbead capture
      was achieved with almost 100% yield within 1 min, and all the beads were
      retrieved in 10 s. Lysozyme or thrombin binding aptamer labelled microbeads were
      trapped on the proposed bead microarray, and the in situ fluorescence signal of
      the bead array was monitored after aptamer-target protein interaction. The
      protein-aptamer conjugated microbeads were recovered, and the aptamer was
      isolated for matrix assisted laser desorption/ionization time-of-flight mass
      spectrometry analysis to confirm the identity of the aptamer. 

PMID- 25587370
TI  - Diseases of the nose and paranasal sinuses in child.
AB  - Diseases of the pediatric nose and nasal sinuses as well as neighboring
      anatomical structures encompass a variety of pathologies, especially of
      inflammatory nature. Congenital disease, such as malformations and structural
      deviations of the nasal septum, as well as systemic metabolic pathologies
      affecting the nose and sinuses, rarely require medical therapy from an
      Otolaryngologist. The immunological function of the mucosa and genetic factors
      play a role in the development of disease in the pediatric upper airway tract,
      especially due to the constantly changing anatomy in this growth phase. Disease
      description of the nose and nasal sinuses due to mid-facial growth must also take
      developmental age differences (infant, toddler, preschool, and school age) into
      account. Epidemiological examinations and evidence based studies are often
      lacking in the pediatric population. The wide range of inflammatory diseases of
      the nose and paranasal sinuses, such as the acute and chronic rhinosinusitis, the
      allergic rhinitis, and adenoid disease, play a role in the susceptibility of a
      child to infection. The susceptibility to infection depends on the pediatric age
      structure (infant, young child) and has yet to be well defined. The acute
      rhinosinusitis in children develops after a viral infection of the upper airways,
      also referred to as the "common cold" in the literature. It usually spontaneously
      heals within ten days without any medical therapy. Antibiotic therapy is prudent
      in complicated episodes of ARS. The antibiotic therapy is reserved for children
      with complications or associated disease, such as bronchial asthma and/or chronic
      bronchitis. A chronic rhinosinusitis is defined as the inflammatory change in the
      nasal mucosa and nasal sinus mucosa, in which the corresponding symptoms persist
      for over 12 weeks. The indication for CT-imaging of the nasal sinuses is reserved
      for cases of chronic rhinosinusitis that have been successfully treated with
      medication. A staged therapeutic concept is followed in CRS based on conservative
      and surgical methods. Nasal sinus surgery is considered nowadays as effective and
      safe in children. Based on the assumption that adenoids are a reservoir for
      bacteria, from which recurrent infections of the nose and nasal sinus originate,
      the adenoidectomy is still defined as a cleansing procedure in rhinosinusitis.
      69.3% of the children had benefit from adenoidectomy. Comorbidities, such as
      pediatric bronchial asthma, presently play an even more important role in the
      therapy of rhinosinusitis; therefore, it is often wise to have the support of
      pediatricians. In western European countries 40% of children presently suffer
      from allergic rhinitis, in which pronounced nasal obstruction can cause disturbed
      growth in facial bones. An early therapy with SIT may prevent the development of
      bronchial asthma and secondary sensitization to other allergens. Therefore, SIT
      is recommended in treatment of allergic rhinitis whenever, if possible. The
      assessment of diagnostic tools is for the examiner not often possible due to the
      lack of evidence. Rhinosurgical approaches are often described in study reports;
      however, they lack the standard prospective randomized long-term study design
      required nowadays and can only be evaluated with caution in the literature. 

PMID- 25587375
TI  - Protein and cell patterning in closed polymer channels by photoimmobilizing
      proteins on photografted poly(ethylene glycol) diacrylate.
AB  - Definable surface chemistry is essential for many applications of microfluidic
      polymer systems. However, small cross-section channels with a high surface to
      volume ratio enhance passive adsorption of molecules that depletes active
      molecules in solution and contaminates the channel surface. Here, we present a
      one-step photochemical process to coat the inner surfaces of closed microfluidic
      channels with a nanometer thick layer of poly(ethylene glycol) (PEG), well known
      to strongly reduce non-specific adsorption, using only commercially available
      reagents in an aqueous environment. The coating consists of PEG diacrylate
      (PEGDA) covalently grafted to polymer surfaces via UV light activation of the
      water soluble photoinitiator benzoyl benzylamine, a benzophenone derivative. The
      PEGDA coating was shown to efficiently limit the adsorption of antibodies and
      other proteins to <5% of the adsorbed amount on uncoated polymer surfaces. The
      coating could also efficiently suppress the adhesion of mammalian cells as
      demonstrated using the HT-29 cancer cell line. In a subsequent equivalent process
      step, protein in aqueous solution could be anchored onto the PEGDA coating in
      spatially defined patterns with a resolution of <15 MUm using an inverted
      microscope as a projection lithography system. Surface patterns of the cell
      binding protein fibronectin were photochemically defined inside a closed
      microfluidic device that was initially homogeneously coated by PEGDA. The
      resulting fibronectin patterns were shown to greatly improve cell adhesion
      compared to unexposed areas. This method opens for easy surface modification of
      closed microfluidic systems through combining a low protein binding PEG-based
      coating with spatially defined protein patterns of interest. 

PMID- 25587371
TI  - Diseases of the middle ear in childhood.
AB  - Middle ear diseases in childhood play an important role in daily ENT practice due
      to their high incidence. Some of these like acute otitis media or otitis media
      with effusion have been studied extensively within the last decades. In this
      article, we present a selection of important childhood middle ear diseases and
      discuss the actual literature concerning their treatment, management of
      complications and outcome. Another main topic of this paper deals with the
      possibilities of surgical hearing rehabilitation in childhood. The bone-anchored
      hearing aid BAHA((r)) and the active partially implantable device Vibrant
      Soundbridge((r)) could successfully be applied for children. In this manuscript,
      we discuss the actual literature concerning clinical outcomes of these
      implantable hearing aids. 

PMID- 25587374
TI  - Inducing chemotactic and haptotactic cues in microfluidic devices for three
      dimensional in vitro assays.
AB  - Microfluidic devices allow for the production of physiologically relevant
      cellular microenvironments by including biomimetic hydrogels and generating
      controlled chemical gradients. During transport, the biomolecules interact in
      distinct ways with the fibrillar networks: as purely diffusive factors in the
      soluble fluid or bound to the matrix proteins. These two main mechanisms may
      regulate distinct cell responses in order to guide their directional migration:
      caused by the substrate-bound chemoattractant gradient (haptotaxis) or by the
      gradient established within the soluble fluid (chemotaxis). In this work 3D
      diffusion experiments, in combination with ELISA assays, are performed using
      microfluidic platforms in order to quantify the distribution of PDGF-BB and TGF
      beta1 across collagen and fibrin gels. Furthermore, to gain a deeper
      understanding of the fundamental processes, the experiments are reproduced by
      computer simulations based on a reaction-diffusion transport model. This model
      yields an accurate prediction of the experimental results, confirming that
      diffusion and binding phenomena are established within the microdevice. 

PMID- 25587376
TI  - A microfluidic manifold with a single pump system to generate highly mono
      disperse alginate beads for cell encapsulation.
AB  - Cell encapsulation technology is a promising strategy applicable to tissue
      engineering and cell therapy. Many advanced microencapsulation chips that
      function via multiple syringe pumps have been developed to generate mono-disperse
      hydrogel beads encapsulating cells. However, their operation is difficult and
      only trained microfluidic engineers can use them with dexterity. Hence, we
      propose a microfluidic manifold system, driven by a single syringe pump, which
      can enable the setup of automated flow sequences and generate highly mono
      disperse alginate beads by minimizing disturbances to the pump pressure. The
      encapsulation of P19 mouse embryonic carcinoma cells and embryonic body formation
      are demonstrated to prove the efficiency of the proposed system. 

PMID- 25587377
TI  - Erratum: Publisher's Note: "Inducing chemotactic and haptotactic cues in
      microfluidicdevices for three-dimensional in vitro assays" [Biomicrofluidics 8,
      064122 (2014)].

PMID- 25587378
TI  - Correlation between serum RANTES levels and the severity of Parkinson's disease.
AB  - Inflammatory mediators may reflect a role of systemic inflammation in the
      neurodegenerative process of Parkinson's disease (PD). Interleukin-6 (IL-6) and
      chemokine ligand 5 (CCL5), also known as RANTES (regulated on activation, normal
      T cell expressed and secreted), have been implicated in neurodegenerative
      diseases including PD. Serum levels of RANTES and IL-6 of 78 consecutive PD
      patients and age-matched 80 controls were measured. Patients with PD had higher
      RANTES and IL-6 levels compared with the controls. We found that serum RANTES
      levels strongly correlated with Hoehn-Yahr score and disease duration in PD
      patients. This study indicated that patients with PD have an on-going systemic
      inflammatory profile where the elevated peripheral production of RANTES may play
      a role in the neurodegenerative process. 

PMID- 25587379
TI  - Efficacy of Connective Tissue with and without Periosteum in Regeneration of
      Intrabony Defects.
AB  - Background and aims. Connective tissue grafts with and without periosteum is used
      in regenerative treatments of bone and has demonstrated successful outcomes in
      previous investigations. The aim of present study was to evaluate the
      effectiveness of connective tissue graft with and without periosteum in
      regeneration of intrabony defects. Materials and methods. In this single-blind
      randomized split-mouth clinical trial, 15 pairs of intrabony defects in 15
      patients with moderate to advanced periodontitis were treated by periosteal
      connective tissue graft + ABBM (test group) or non-periosteal connective tissue
      graft + ABBM (control group). Probing pocket depth, clinical attachment level,
      free gingival margin position, bone crestal position, crest defect depth and
      defect depth to stent were measured at baseline and after six months by surgical
      re-entry. Data was analyzed by Student's t-test and paired t-tests (alpha=0.05).
      Results. Changes in clinical parameters after 6 months in the test and control
      groups were as follows: mean of PPD reduction: 3.1+/-0.6 (P<0.0001); 2.5+/-1.0 mm
      (P<0.0001), CAL gain: 2.3+/-0.9 (P<0.0001); 2.2+/-1.0 mm (P<0.0001), bone fill:
      2.2+/-0.7 mm (P<0.0001); 2.2+/-0.7 mm (P<0.0001), respectively. No significant
      differences in the position of free gingival margin were observed during 6 months
      compared to baseline in both groups. Conclusion. Combinations of periosteal
      connective tissue graft + ABBM and non-periosteal connective tissue graft + ABBM
      were similarly effective in treating intrabony defects without any favor for any
      group. Connective tissue and perio-steum can be equally effective in regeneration
      of intrabony defects. 

PMID- 25587380
TI  - Effect of TiO2 Nanoparticles on Tensile Strength of Dental Acrylic Resins.
AB  - Background and aims. Adding further fillers to dental resins may enhance their
      physical characteristics. The aim of this study was to evaluate the tensile
      strength of heat-curing acrylic resin reinforced by TiO2nanoparticles added into
      the resin matrix. Materials and methods. Commercially available TiO2
      nanoparticles were obtained and characterized using X-ray diffrac-tion (XRD) and
      scanning electron microscopy (SEM) to determine their crystalline structure,
      particle size and morphology. TiO2-acrylic resin nanocomposite was prepared by
      mixing 0.5, 1 and 2 (wt%) of surface modified TiO2 nanoparticles in an
      amalgamator providing three groups of samples. Before curing, the obtained paste
      was packed into steel molds. After cur-ing, the specimens were removed from the
      molds. The tensile strength test samples were prepared according to ISO 1567.
      Results. Two crystalline phases were found in TiO2 nanoparticles including: (i)
      anatase as the major one, and (ii) rutile. The average particle size calculated
      according to the Scherrer equation was 20.4 nm, showing a normal size
      distribution. According to SEM images, the nanocomposite with 1wt% TiO2
      nanoparticles had a better distribution compared to other groups. In addition,
      the group by 1wt% TiO2 exhibited higher tensile strength with a significant
      difference compared to other groups. ANOVA showed significant differences between
      the contents of TiO2 particles in acrylic resin (F = 22.19; P < 0.001).
      Conclusion. A considerable increase in tensile strength was observed with titania
      NPs reinforcement agents in 1wt% by weight. Further increase of TiO2
      nanoparticles decreased the tensile strength. 

PMID- 25587381
TI  - In Vitro Comparison of Compressive and Tensile Strengths ofAcrylic Resins
      Reinforced by Silver Nanoparticles at 2% and0.2% Concentrations.
AB  - Background and aims. Polymethyl methacrylate, PMMA, is widely used in
      prosthodontics for fabrication of removable prostheses. This study was undertaken
      to investigate the effect of adding silver nanoparticles (AgNPs) to PMMA at 2%
      and 0.2% concentrations on compressive and tensile strengths of PMMA. Materials
      and methods. The silver nanoparticles were mixed with heat-cured acrylic resin in
      an amalgamator in two groups at 0.2 and 2 wt% of AgNPs. Eighteen 2*20*200-mm
      samples were prepared for tensile strength test, 12 samples containing silver
      nanoparticle and 6 samples for the control group. Another 18 cylindrical 25*38-mm
      samples were prepared for compressive strength test. Scanning electron microscopy
      was used to verify homogeneous distribution of particles. The powder was manually
      mixed with a resin monomer and then the mixture was properly blended. Before
      curing, the paste was packed into steel molds. After curing, the specimens were
      removed from the molds. One-way ANOVA was used for statistical analysis, followed
      by multiple comparison test (Scheffe's test). Results. This study showed that the
      mean compressive strength of PMMA reinforced with AgNPs was significantly higher
      than that of the unmodified PMMA (P<0.05). It was not statistically different
      between the two groups reinforced with AgNPs. The tensile strength was not
      significantly different between the 0.2% group and unmodified PMMA and it de
      creased significantly after incorporation of 2% AgNPs (P<0.05). Conclusion. Based
      on the results and the desirable effect of nanoparticles of silver on improvement
      of compressive strength of PMMA, use of this material with proper concentration
      in the palatal area of maxillary acrylic resin dentures is recommended. 

PMID- 25587382
TI  - Effect of Sodium Ascorbate and Delayed Bonding on the Bond Strength of Silorane
      and Two-step Self-etch Adhesive Systems in Bleached Enamel.
AB  - Background and aims. Studies have shown decreased bond strength of composite
      resin to human and bovine bleached enamel. This study evaluated the effect of
      sodium ascorbate and delayed bonding on the bond strength of two adhesive systems
      to bleached enamel. Materials and methods. The labial surfaces of 150 sound
      bovine incisor teeth were abraded with abrasive paper. The teeth were randomly
      divided into 8 groups: A: control; B: bleached with 35% hydrogen peroxide; C:
      bleached with 35% hydrogen peroxide + sodium ascorbate gel; and D: bleached with
      35% hydrogen peroxide + delayed bonding. In groups A-D, silorane adhesive system
      and Filtek silorane composite resin were used. In groups E-H, the same
      preparation methods of groups A-D were used. Two-step self-etch Clearfil SE Bond
      adhesive systems and AP-X composite resin were administered. Shear bond strength
      of each group was measured. Two samples were prepared for each surface
      preparation for ultra-structural evaluation. Two-way ANOVA and Tukey test were
      used for data analysis at P<0.05. Results. The interaction between the adhesive
      system type and surface preparation protocol was significant (P=0.014),
      withsignificant differences in shear bond strengths in terms of the adhesive
      systems (P<0.01). There were significant differences in shear bond strength in
      terms of surface preparation techniques irrespective of the adhesive system
      (P<0.01). Conclusion. The results showed that bleaching with 35% hydrogen
      peroxide decreased the shear bond strength values with both adhesive systems, and
      a one-week delay in bonding and 10% sodium ascorbate for10 minutes restored the
      bond strength in both adhesive systems. 

PMID- 25587383
TI  - In vitro investigation of heat transfer phenomenon in human immature teeth.
AB  - Background and aims. Heat generated within tooth during clinical dentistry can
      cause thermally induced damage to hard and soft components of the tooth (enamel,
      dentin and pulp). Geometrical characteristics of immature teeth are different
      from those of mature teeth. The purpose of this experimental and theoretical
      study was to investigate thermal changes in immature permanent teeth during the
      use of LED light-curing units (LCU). Materials and methods. This study was
      performed on the second mandibular premolars. This experimental investiga-tion
      was carried out for recording temperature variations of different sites of tooth
      and two dimensional finite element models were used for heat transfer phenomenon
      in immature teeth. Sensitivity analysis and local tests were included in the
      model validation phase. Results. Overall, thermal stimulation for 30 seconds with
      a low-intensity LED LCU increased the temperature from 28 degrees C to 38 degrees
      C in IIT (intact immature tooth) and PIT (cavity-prepared immature tooth). When a
      high-intensity LED LCU was used, tooth temperature increased from 28 degrees C to
      48 degrees C. The results of the experimental tests and mathematical modeling
      illustrated that using LED LCU on immature teeth did not have any detrimental
      effect on the pulp temperature. Conclusion. Using LED LCU in immature teeth had
      no effect on pulp temperature in this study. Sensitivity analysis showed that
      variations of heat conductivity might affect heat transfer in immature teeth;
      therefore, further studies are required to determine thermal conductivity of
      immature teeth. 

PMID- 25587384
TI  - Antibacterial Effect of All-in-one Self-etch Adhesives on Enterococcus faecalis.
AB  - Background and aims. The aim of this study was to evaluate the antibacterial
      activity of one-step self-etch adhesives on Enterococcus faecalis on days 1, 7
      and 14 with the use of modified direct contact test. Materials and methods. The
      modified directcontact test was used to evaluate the antibacterial effect of
      Adper Easy One, Bond Force, Clearfil S3 Bond, Futurabond M, G-Bond, iBond and
      OptiBond All-in-one adhesives on Enterococcus faecalis after aging the samples in
      phosphate-buffered saline for one, seven and fourteen days. Data were analyzed
      using one-way ANOVA and post hoc Tukey tests. Aging effect of each adhesive was
      evaluated by paired-sample test. In this study, P<0.05 was considered
      significant. Results. All the tested adhesives exhibited antibacterial activity
      after one day and had significant differences with the positive control group
      (P<0.05). After one week, OptiBond All-in-one, iBond and Futurabond M exhibited
      significant differences in bacterial growth from other groups (P<0.05). There
      were no significant differences between the groups in two weeks (P>0.05).
      Conclusion. iBond exhibited the highest antibacterial effect on E. faecalis after
      one week. Futurabond and OptiBond All-in-one exhibited antibacterial effects
      against E. faecalis for one week. 

PMID- 25587385
TI  - Oral health related quality of life in diabetic patients.
AB  - Background and aims. Diabetic patients display an increased risk of oral
      disorders, and oral health related quality of life (OHRQL) might affect their
      management and treatment modalities. The aim of the present study was to
      determine OHRQL and associated parameters in patients with diabetes. Materials
      and methods. In this study two hundred patients were recruited from the diabetes
      clinic in Mustafa Khomeini Hospital in Tehran, Iran. OHRQL was assessed using
      Oral Health Impact Profile Questionnaire (OHIP-20). Also, another questionnaire
      was designed which contained questions regarding participants' knowledge about
      oral complications of diabetes and oral health behavior. OHRQL was categorized as
      low and good. Data were analyzed using logistic regression at P = 0.05. Results.
      Of the diabetic patients assessed, 77.5% were in good and 22.5% were in low
      categories of OHRQL. This quality was significantly associated with age (OR =
      4.03, 95% CI = 1.63-11.29), knowledge about diabetes oral complications (OR =
      18.17 95% CI = 4.42-158.6), educational level (OR = 26.31 95% CI = 4.2-1080.3),
      referred for dental visit by physician (OR = 3.16 95% CI = 1.48-6.69), frequency
      of brushing (OR = 10.29 95% CI = 3.96-31.2) and length of time diagnosed with
      diabetes (OR = 6.21 95% CI = 2.86-13.63). Conclusion. Oral health related quality
      of life was not negatively affected by diabetes mellitus in the assessed sample. 

PMID- 25587387
TI  - CD56 Expression in Odontogenic Cysts and Tumors.
AB  - Background and aims. Odontogenic cysts and tumors have a wide spectrum of
      clinical characteristics that lead to the different management strategies. Since
      definite diagnosis is difficult in some cases, it has been suggested that CD56
      may be a candidate marker for definitive diagnosis of some odontogenic tumors.
      The present study was designed to examine CD56 expression in lesions with
      histopathological similarities. Materials and methods. In this cross-sectional,
      analytical study the subjects were 22 ameloblastomas, 13 dentigerous cysts, 10
      keratocystic odontogenic tumors (KCOT), 4 adenomatoid odontogenic tumors (AOT), 3
      orthokeratinized odonto-genic cysts, 3 calcifying odontogenic cysts (COC) and one
      glandular odontogenic cyst (GOC). All the samples were examined for CD56
      immunoreactivity. Data were analyzed using chi-square test. Results. Twenty cases
      (91%) of ameloblastomas, 3 (75%) AOT, 4 (40%) KCOT and one case of GOC were
      positive for CD56. None of the dentigerous cysts, COC and orthokeratinized
      odontogenic cysts was CD56-positive. There was a significant difference in the
      CD56 expression between ameloblastoma and dentigerous cyst, as well as COC. Also,
      KCOT showed significantly higher expression than orthokeratinized odontogenic
      cyst. Conclusion. In this study CD56 expression was limited to the odontogenic
      tumors and more aggressive cystic lesions. This marker can be a useful aid for
      distinguishing cysts and tumors from similar lesions. 

PMID- 25587386
TI  - Effect of Iranian Propolis on Salivary Total Antioxidant Capacity in Gamma
      irradiated Rats.
AB  - Background and aims. The antioxidant and anti-inflammatory properties of propolis
      were studied. Since saliva containsantioxidants and radiotherapy of the head and
      neck mainly affects the saliva, salivary antioxidant defensive mechanism
      iscompromised with oxidative stress produced by radiation therapy. Therefore, the
      aim of the present study was to investigatethe effect of propolis on salivary
      total antioxidant capacity in irradiated rats. Materials and methods. The study
      was conducted on 28 rats, 7-11 weeks of age (160+/-20 g), divided into four
      groups:saline with no radiation (S), saline and radiation (SR), propolis with no
      radiation (P) [400 mg/kg IP], propolis and radiation(PR) [400 mg/kg IP]. SP and
      PR were exposed to 15 Gy of gamma irradiation for 7 minutes and 39 seconds. The
      rats received intraperitoneal injections each day for 10 days, and their tongues
      and lips were daily examined for mucositis; salivasample were also taken three
      times on days 0, 6, and 10. Results. Mucositis incidence appeared to be delayed
      in the PR compared to the SR, and the severity was significantlyhigher in the SR
      compared to the PR. No significant alterations were observed in salivary
      antioxidant levels during the ex-periment, except the SR group in which a
      significant reduction was found. Conclusion. Propolis might reduce and delay
      radiation-induced mucositis in animal models; it might be able to prevent
      thereduction in salivary antioxidant levels in irradiated rats as well. 

PMID- 25587388
TI  - The efficacy of magnetic resonance imaging and color Doppler ultrasonography in
      diagnosis of salivary gland tumors.
AB  - Background and aims. Although salivary gland tumors are not very common, early
      diagnosis and treatment is crucial because of their proximity to vital organs,
      and therefore, determining the efficacy of new imaging procedures becomes
      important. This study aimed to evaluate the efficacy of magnetic resonance
      imaging (MRI) and color doppler ultrasonography parameters in the diagnosis and
      differentiation of benign and malignant salivary gland tumors. Materials and
      methods. In this cross-sectional study, color doppler ultrasonography and MRI
      were performed for 22 patients with salivary gland tumor. Demographic data as
      well as MRI, color doppler ultrasonography, and surgical parameters including
      tumor site, signal in MRI images, ultrasound echo, tumor border, lymphadenopathy,
      invasion, perfusion, vascular resistance index (RI), vascular pulse index (PI)
      were analyzed using Chi-square test, Fisher's exact test, and independent t-test.
      Results. The mean age of patients was 46.59+/-13.97 years (8 males and
      14females). Patients with malignant tumors were older (P < 0.01). The most common
      tumors were pleomorphic adenoma (36.4%), metastasis (36.4%), and mucoepidermoid
      carcinoma (9%). Nine tumors (40.9%) were benign and 13 (59.1%) were malignant.
      The overall accuracy of MRI and color doppler ultrasonography in determining
      tumor site was 100% and 95%, respectively. No significant difference observed
      between RI and PI and the diagnosis of tumor. Conclusion. Both MRI and
      ultrasonography have high accuracy in the localization of tumors. Well-identified
      border was a sign of benign tumors. Also, invasion to adjacent structures was a
      predictive factor for malignancy. 

PMID- 25587389
TI  - Micro-leakage of a Fissure Sealant Cured Using Quartz-tungsten-halogen and Plasma
      Arc Light Curing Units.
AB  - Background and aims. Newer curing units such as plasma arc can polymerize the
      sealants in much shorter curing times. The aim of this study was to compare the
      effect of two different curing units on the micro-leakage of a fissure sealant
      material. Materials and methods. Sixty two extracted premolars without caries
      were randomly divided into two groups of 31 samples. Occlusal surfaces of all
      teeth were cleansed. Then, teeth surfaces were etched by 37% phosphoric acid.
      After rinsing and drying, occlusal surfaces of teeth were sealed by a fissure
      sealant. The sealant was then cured using either a halogen light curing unit or a
      plasma arc curing light. After sealing, the teeth were thermocycled for 500
      cycles. The teeth were then sectioned and examined for micro-leakage. Statistical
      analyses were performed with Mann-Whitney test. Results. There was no significant
      difference between two groups regarding micro-leakage (P = 0.42). Conclusion.
      Results showed that there was no significant difference between two different
      curing units. Therefore, plasma arc unit might be a useful alternative for
      sealant polymerization. 

PMID- 25587390
TI  - Rehabilitation of a partial nasal defect with facial prosthesis: a case report.
AB  - >Malignancies of the midface result in cosmetic deformities that make
      maxillofacial prosthesis as an integral part of the treatment plan. Facial
      defects can be devastating in their impact on physical structure and function of
      the affected individual, leading to potentional compromises in quality of life.
      Reconstruction of nasal defects is a challenge for the prosthodontist because of
      esthetic and retention problems associated with the facial prosthesis. This paper
      reports the rehabilitation of a partial nasal defect caused by basal cell
      carcinoma treatment using a nasal prosthesis made with silicone elastomers and
      mechanical and anatomical retentive aids. The patient had no problem with the
      prosthesis, except for a partial loss of extrinsic coloration in the two-year
      follow-up. 

PMID- 25580220
TI  - The second touch hypothesis: T cell activation, homing and polarization.
AB  - The second touch hypothesis states that T cell activation, proliferation,
      induction of homing receptors and polarization are distinguishable and, at least
      in part, sequential. The second touch hypothesis maintains that full T cell
      polarization requires T cell interaction with antigen-presenting cells (DCs,
      macrophages, B cells and certain activated stromal cells) in the non-lymphoid
      tissue where the antigen resides. Upon initial antigen encounter in peripheral
      lymph nodes (PLN), T cells become activated, proliferate and express homing
      receptors that enable them to recirculate to the (inflamed) tissue that contains
      the antigen. Differentiation into the T helper lineages Th1, Th2, Th17 and
      induced regulatory T cells (iTreg) requires additional antigen presentation by
      tissue macrophages and other antigen presenting cells (APCs) in the inflamed
      tissue. Here, I present a conceptual framework for the importance of peripheral
      (non-lymphoid) antigen presentation to antigen-experienced T cells. 

PMID- 25587392
TI  - Preclinical screening for acute toxicity of therapeutic monoclonal antibodies in
      a hu-SCID model.
AB  - Monoclonal antibodies (mAbs) have been a spectacular clinical and commercial
      success in the treatment of cancer and autoimmune diseases. Many of these mAbs
      (for example, OKT3, Campath-1H, rituximab and infliximab) are against surface or
      secreted products of lymphocytes. However, mAbs can have a variety of adverse
      effects including fever, chills and nausea. This is probably a result of cytokine
      release, which is most seriously manifested as a 'cytokine storm' as highlighted
      by the TGN1412 (anti-CD28) trial. Prediction of adverse effects of mAbs would be
      clinically advantageous and numerous in vitro assays attempting to predict
      adverse effects have been reported. Here, we report an in vivo humanized mouse
      model to detect adverse effects in response to OKT3, Campath-1H or the polyclonal
      Ab preparation anti-thymocyte globulin. We found that the administration of each
      of these Abs to humanized mice led to acute clinical symptoms such as
      piloerection, hypomotility and hypothermia, particularly when delivered via the
      intravenous route. A cytokine storm occurred in the humanized mice receiving
      OKT3. This model system is a potentially useful tool to predict adverse effects
      and select initial doses for first-in-human trials. We would advocate this in
      vivo model, in addition to current in vitro preclinical testing, as a more
      representative and robust means of assessing potential adverse effects of mAb
      before their human use. 

PMID- 25587393
TI  - Performance evaluation of a scoria-compost biofilter treating xylene vapors.
AB  - The removal of xylene vapors was studied in a biofilter packed with a new hybrid
      (scoria/compost) packing material at various inlet loads (IL) and empty bed
      residence times (EBRT) of 90, 60, and 40s. The best performance was observed for
      EBRT of 90s, where a removal efficiency of 98% was obtained under steady state
      condition for inlet xylene concentration of 1.34 g m(-3), while a maximum
      elimination capacity of 97.5 g m(-3) h(-1) was observed for IL of 199.5 g m(-3)
      h(-1). Carbon dioxide production rates and the microbial counts for xylene
      degraders followed xylene elimination capacities. Overall look to the results of
      this study indicates that the scoria/compost mixture could be considered as a
      potential biofilter carrier, with low pressure drop (here <4 mm H2O), to treat
      air streams containing VOCs. 

PMID- 25587395
TI  - Welcome to biosensors: a new open-access journal.
AB  - The journal Biosensors has been started as a peer-reviewed, open access journal.
      As editors, we believe that it will fulfill an important role in the community of
      researchers and developers in the field of biosensors. The addition of a "free
      access" journal to the existing, high quality publications in this field is
      something that we believe is very important in a field which is now so entwined
      with commercial activity and where researchers aim, not only at academic
      research, but on the development of products at a potentially massive scale. For
      these researchers, it is important that they can publish their results in a
      journal that guarantees quality that comes from peer-review, but that at the same
      time breaks the traditional boundaries of academic journals which need a
      subscription or a pay-per-view option to access the published data. 

PMID- 25587394
TI  - Fast Pure R Implementation of GEE: Application of the Matrix Package.
AB  - Generalized estimating equation solvers in R only allow for a few pre-determined
      options for the link and variance functions. We provide a package, geeM, which is
      implemented entirely in R and allows for user specified link and variance
      functions. The sparse matrix representations provided in the Matrix package
      enable a fast implementation. To gain speed, we make use of analytic inverses of
      the working correlation when possible and a trick to find quick numeric inverses
      when an analytic inverse is not available. Through three examples, we demonstrate
      the speed of geeM, which is not much worse than C implementations like geepack
      and gee on small data sets and faster on large data sets.

PMID- 25587396
TI  - Application of paper-supported printed gold electrodes for impedimetric
      immunosensor development.
AB  - In this article, we report on the formation and mode-of-operation of an affinity
      biosensor, where alternate layers of biotin/streptavidin/biotinylated-CRP
      antigen/anti-CRP antibody are grown on printed gold electrodes on disposable
      paper-substrates. We have successfully demonstrated and detected the formation of
      consecutive layers of supra-molecular protein assembly using an electrical
      (impedimetric) technique. The formation process is also supplemented and verified
      using conventional surface plasmon resonance (SPR) measurements and surface
      sensitive characterization techniques, such as X-ray photoelectron spectroscopy
      (XPS) and atomic force microscopy (AFM). The article provides a possible
      biosensor development scheme, where-(1) fabrication of paper substrate (2)
      synthesis of gold nanoparticle inks (3) inkjet printing of gold electrodes on
      paper (4) formation of the biorecognition layers on the gold electrodes and (5)
      electrical (impedimetric) analysis of growth-all are coupled together to form a
      test-structure for a recyclable and inexpensive point-of-care diagnostic
      platform. 

PMID- 25587398
TI  - Quinone-based polymers for label-free and reagentless electrochemical
      immunosensors: application to proteins, antibodies and pesticides detection.
AB  - Polyquinone derivatives are widely recognized in the literature for their
      remarkable properties, their biocompatibility, simple synthesis, and easy bio
      functionalization. We have shown that polyquinones present very stable
      electroactivity in neutral aqueous medium within the cathodic potential domain
      avoiding side oxidation of interfering species. Besides, they can act as
      immobilized redox transducers for probing biomolecular interactions in sensors.
      Our group has been working on devices based on such modified electrodes with a
      view to applications for proteins, antibodies and organic pollutants using a
      reagentless label-free electrochemical immunosensor format. Herein, these
      developments are briefly reviewed and put into perspective. 

PMID- 25587399
TI  - Single step nanoplasmonic immunoassay for the measurement of protein biomarkers.
AB  - A nanoplasmonic biosensor for highly-sensitive, single-step detection of protein
      biomarkers is presented. The principle is based on the utilization of the optical
      scattering properties of gold nanorods (GNRs) conjugated to bio-recognition
      molecules. The nanoplasmonic properties of the GNRs were utilized to detect
      proteins using near-infrared light interferometry. We show that the antibody
      conjugated GNRs can specifically bind to our model analyte, Glucose Transporter-1
      (Glut-1). The signal intensity of back-scattered light from the GNRs bound after
      incubation, correlated well to the Glut-1 concentration as per the calibration
      curve. The detection range using this nanoplasmonic immunoassay ranges from 10
      ng/mL to 1 ug/mL for Glut-1. The minimal detectable concentration based on the
      lowest discernable concentration from zero is 10 ng/mL. This nanoplasmonic
      immunoassay can act as a simple, selective, sensitive strategy for effective
      disease diagnosis. It offers advantages such as wide detection range, increased
      speed of analysis (due to fewer incubation/washing steps), and no label
      development as compared to traditional immunoassay techniques. Our future goal is
      to incorporate this detection strategy onto a microfluidic platform to be used as
      a point-of-care diagnostic tool. 

PMID- 25587397
TI  - Isothermal amplification methods for the detection of nucleic acids in
      microfluidic devices.
AB  - Diagnostic tools for biomolecular detection need to fulfill specific requirements
      in terms of sensitivity, selectivity and high-throughput in order to widen their
      applicability and to minimize the cost of the assay. The nucleic acid
      amplification is a key step in DNA detection assays. It contributes to improving
      the assay sensitivity by enabling the detection of a limited number of target
      molecules. The use of microfluidic devices to miniaturize amplification protocols
      reduces the required sample volume and the analysis times and offers new
      possibilities for the process automation and integration in one single device.
      The vast majority of miniaturized systems for nucleic acid analysis exploit the
      polymerase chain reaction (PCR) amplification method, which requires repeated
      cycles of three or two temperature-dependent steps during the amplification of
      the nucleic acid target sequence. In contrast, low temperature isothermal
      amplification methods have no need for thermal cycling thus requiring simplified
      microfluidic device features. Here, the use of miniaturized analysis systems
      using isothermal amplification reactions for the nucleic acid amplification will
      be discussed. 

PMID- 25587400
TI  - Biomimetic strategies for sensing biological species.
AB  - The starting point of modern biosensing was the application of actual biological
      species for recognition. Increasing understanding of the principles underlying
      such recognition (and biofunctionality in general), however, has triggered a
      dynamic field in chemistry and materials sciences that aims at joining the best
      of two worlds by combining concepts derived from nature with the processability
      of manmade materials, e.g., sensitivity and ruggedness. This review covers
      different biomimetic strategies leading to highly selective (bio)chemical
      sensors: the first section covers molecularly imprinted polymers (MIP) that
      attempt to generate a fully artificial, macromolecular mold of a species in order
      to detect it selectively. A different strategy comprises of devising polymer
      coatings to change the biocompatibility of surfaces that can also be used to
      immobilized natural receptors/ligands and thus stabilize them. Rationally
      speaking, this leads to self-assembled monolayers closely resembling cell
      membranes, sometimes also including bioreceptors. Finally, this review will
      highlight some approaches to generate artificial analogs of natural recognition
      materials and biomimetic approaches in nanotechnology. It mainly focuses on the
      literature published since 2005. 

PMID- 25587401
TI  - Fast and Sensitive Interferon-gamma Assay Using Supercritical Angle Fluorescence.
AB  - We present an immunoassay for Interferon-gamma (IFN-gamma) with a limit of
      detection of 1.9 pM (30 pg/mL) and a linear concentration range spanning three
      orders of magnitude. The developed one-step assay takes only 12 min and can
      replace the time-consuming and labor-intensive enzyme-linked immunosorbent assay
      (ELISA). The solid-phase sandwich assay is performed on a new measurement system
      comprising single-use test tubes and a compact fluorescence reader. The polymer
      tubes contain an optical configuration for the detection of supercritical angle
      fluorescence, allowing for highly sensitive real-time binding measurements. 

PMID- 25587402
TI  - Special issue on organic electronic bio-devices.
AB  - The aim of the present editorial is to briefly summarize the current scientific
      and technological accomplishments in the field of organic electronic biosensors
      as described in the articles published in this Special Issue. By definition, a
      biosensor is a robust analytical device that combines a biological recognition
      element (e.g., antibodies, enzymes, cells) with a transducer. Organic electronic
      bio-devices are considered as potentially reliable substitutes of conventional
      and rather expensive analytical techniques employed for several applications such
      as medical diagnosis, food safety and environment pollution monitoring. Some
      insights into the selection and immobilization of recognition elements, signal
      amplification, fabrication techniques and analytical performance of biosensing
      devices will be presented. 

PMID- 25587403
TI  - Fiber-Optic Fluoroimmunoassay System with a Flow-Through Cell for Rapid On-Site
      Determination of Escherichia coli O157:H7 by Monitoring Fluorescence Dynamics.
AB  - Dynamic fluoroimmunoassay with a flow-through system using optical fiber probes
      consisting of polystyrene was developed and applied to a quantitative detection
      of E. coli O157:H7. The system measures E. coli as fluorescence of sandwich-type
      immune complexes formed by capture antibodies immobilized on the surface of the
      probe, E. coli cells, and fluorescently labeled detection antibodies. Excitation
      was carried out using an evanescent wave from the probe. Resulting fluorescence
      recoupled into the probe was detected by a photodiode. The assay system was
      constructed with a flow cell which was available for sequential injection of
      experimental reagents. In vitro characterization was performed using the flow
      cell, and the calibration range of E. coli O157:H7 was from 10(3) to 10(7)
      cells/mL. The measurement for each sample was completed within 12 min.
      Furthermore, it was also possible to estimate the concentrations of E. coli
      O157:H7 by the increasing rate of fluorescence during binding reaction of
      detection antibodies to antigens. This minimized the time for measurement down to
      6 min. The system is suitable for rapid and direct determination for
      microorganisms or bacteria in food, clinical, and environmental sources. 

PMID- 25587404
TI  - Evaluation of impedance-based label-free technology as a tool for pharmacology
      and toxicology investigations.
AB  - The use of label-free technologies based on electrical impedance is becoming more
      and more popular in drug discovery. Indeed, such a methodology allows the
      continuous monitoring of diverse cellular processes, including proliferation,
      migration, cytotoxicity and receptor-mediated signaling. The objective of the
      present study was to further assess the usefulness of the real-time cell analyzer
      (RTCA) and, in particular, the xCELLigence platform, in the context of early drug
      development for pharmacology and toxicology investigations. In the present
      manuscript, four cellular models were exposed to 50 compounds to compare the cell
      index generated by RTCA and cell viability measured with a traditional viability
      assay. The data revealed an acceptable correlation (ca. 80%) for both cell lines
      (i.e., HepG2 and HepaRG), but a lack of correlation (ca. 55%) for the primary
      human and rat hepatocytes. In addition, specific RTCA profiles (signatures) were
      generated when HepG2 and HepaRG cells were exposed to calcium modulators,
      antimitotics, DNA damaging and nuclear receptor agents, with a percentage of
      prediction close to 80% for both cellular models. In a subsequent experiment,
      HepG2 cells were exposed to 81 proprietary UCB compounds known to be genotoxic or
      not. Based on the DNA damaging signatures, the RTCA technology allowed the
      detection of ca. 50% of the genotoxic compounds (n = 29) and nearly 100% of the
      non-genotoxic compounds (n = 52). Overall, despite some limitations, the
      xCELLigence platform is a powerful and reliable tool that can be used in drug
      discovery for toxicity and pharmacology studies. 

PMID- 25587405
TI  - Study of Immobilization Procedure on Silver Nanolayers and Detection of Estrone
      with Diverged Beam Surface Plasmon Resonance (SPR) Imaging.
AB  - An immobilization protocol was developed to attach receptors on smooth silver
      thin films. Dense and packed 11-mercaptoundecanoic acid (11-MUA) was used to
      avoid uncontrolled sulfidization and harmful oxidation of silver nanolayers. N,N'
      dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide (NHS) were added to make
      the silver surfaces reactive. A comparative study was carried out with different
      immersion times of silver samples in 11-MUA solutions with different
      concentrations to find the optimum conditions for immobilization. The signals,
      during each step of the protocol, were analyzed with a refractometer based on the
      surface plasmon resonance (SPR) effect and luminescence techniques. Molecular
      interactions at the surfaces between the probe and target at the surface
      nanolayer shift the SPR signal, thus indicating the presence of the substance. To
      demonstrate specific biosensing, rabbit anti-estrone polyclonal immunoglobulin G
      (IgG) antibody was immobilized through a linker on 47 nm silver layer deposited
      on SF11 glass. At the final stage, the representative endocrine disruptor-estrone
      was attached and detected in deionized water with a diverging beam SPR imaging
      sensor. 

PMID- 25587406
TI  - Development of a Fluorescence Resonance Energy Transfer (FRET)-Based DNA
      Biosensor for Detection of Synthetic Oligonucleotide of Ganoderma boninense.
AB  - An optical DNA biosensor based on fluorescence resonance energy transfer (FRET)
      utilizing synthesized quantum dot (QD) has been developed for the detection of
      specific-sequence of DNA for Ganoderma boninense, an oil palm pathogen. Modified
      QD that contained carboxylic groups was conjugated with a single-stranded DNA
      probe (ssDNA) via amide-linkage. Hybridization of the target DNA with conjugated
      QD-ssDNA and reporter probe labeled with Cy5 allows for the detection of related
      synthetic DNA sequence of Ganoderma boninense gene based on FRET signals.
      Detection of FRET emission before and after hybridization was confirmed through
      the capability of the system to produce FRET at 680 nm for hybridized sandwich
      with complementary target DNA. No FRET emission was observed for non
      complementary system. Hybridization time, temperature and effect of different
      concentration of target DNA were studied in order to optimize the developed
      system. The developed biosensor has shown high sensitivity with detection limit
      of 3.55 * 10(-9) M. TEM results show that the particle size of QD varies in the
      range between 5 to 8 nm after ligand modification and conjugation with ssDNA.
      This approach is capable of providing a simple, rapid and sensitive method for
      detection of related synthetic DNA sequence of Ganoderma boninense. 

PMID- 25587408
TI  - Microfluidic platform for the elastic characterization of mouse submandibular
      glands by atomic force microscopy.
AB  - The ability to characterize the microscale mechanical properties of biological
      materials has the potential for great utility in the field of tissue engineering.
      The development and morphogenesis of mammalian tissues are known to be guided in
      part by mechanical stimuli received from the local environment, and tissues
      frequently develop to match the physical characteristics (i.e., elasticity) of
      their environment. Quantification of these material properties at the microscale
      may provide valuable information to guide researchers. Presented here is a
      microfluidic platform for the non-destructive ex vivo microscale mechanical
      characterization of mammalian tissue samples by atomic force microscopy (AFM).
      The device was designed to physically hold a tissue sample in a dynamically
      controllable fluid environment while allowing access by an AFM probe operating in
      force spectroscopy mode to perform mechanical testing. Results of measurements
      performed on mouse submandibular gland samples demonstrate the ability of the
      analysis platform to quantify sample elasticity at the microscale, and observe
      chemically-induced changes in elasticity. 

PMID- 25587410
TI  - Microstructured block copolymer surfaces for control of microbe adhesion and
      aggregation.
AB  - The attachment and arrangement of microbes onto a substrate is influenced by both
      the biochemical and physical surface properties. In this report, we develop
      lectin-functionalized substrates containing patterned, three-dimensional
      polymeric structures of varied shapes and densities and use these to investigate
      the effects of topology and spatial confinement on lectin-mediated microbe
      immobilization. Films of poly(glycidyl methacrylate)-block-4,4-dimethyl-2
      vinylazlactone (PGMA-b-PVDMA) were patterned on silicon surfaces into line arrays
      or square grid patterns with 5 MUm wide features and varied pitch. The patterned
      films had three-dimensional geometries with 900 nm film thickness. After surface
      functionalization with wheat germ agglutinin, the size of Pseudomonas fluorescens
      aggregates immobilized was dependent on the pattern dimensions. Films patterned
      as parallel lines or square grids with a pitch of 10 MUm or less led to the
      immobilization of individual microbes with minimal formation of aggregates. Both
      geometries allowed for incremental increases in aggregate size distribution with
      each increase in pitch. These engineered surfaces combine spatial confinement
      with affinity-based capture to control the extent of microbe adhesion and
      aggregation, and can also be used as a platform to investigate intercellular
      interactions and biofilm formation in microbial populations of controlled sizes. 

PMID- 25587407
TI  - Application of a nitric oxide sensor in biomedicine.
AB  - In the present study, we describe the biochemical properties and effects of
      nitric oxide (NO) in intact and dysfunctional arterial and venous endothelium.
      Application of the NO electrochemical sensor in vivo and in vitro in erythrocytes
      of healthy subjects and patients with vascular disease are reviewed. The
      electrochemical NO sensor device applied to human umbilical venous endothelial
      cells (HUVECs) and the description of others NO types of sensors are also
      mentioned. 

PMID- 25587411
TI  - Asynchronous Magnetic Bead Rotation (AMBR) Microviscometer for Label-Free DNA
      Analysis.
AB  - We have developed a label-free viscosity-based DNA detection system, using
      paramagnetic beads as an asynchronous magnetic bead rotation (AMBR)
      microviscometer. We have demonstrated experimentally that the bead rotation
      period is linearly proportional to the viscosity of a DNA solution surrounding
      the paramagnetic bead, as expected theoretically. Simple optical measurement of
      asynchronous microbead motion determines solution viscosity precisely in
      microscale volumes, thus allowing an estimate of DNA concentration or average
      fragment length. The response of the AMBR microviscometer yields reproducible
      measurement of DNA solutions, enzymatic digestion reactions, and PCR systems at
      template concentrations across a 5000-fold range. The results demonstrate the
      feasibility of viscosity-based DNA detection using AMBR in microscale aqueous
      volumes. 

PMID- 25587412
TI  - Hierarchical thin film architectures for enhanced sensor performance: liquid
      crystal-mediated electrochemical synthesis of nanostructured imprinted polymer
      films for the selective recognition of bupivacaine.
AB  - Nanostructured bupivacaine-selective molecularly imprinted 3-aminophenylboronic
      acid-p-phenylenediamine co-polymer (MIP) films have been prepared on gold-coated
      quartz (Au/quartz) resonators by electrochemical synthesis under cyclic
      voltammetric conditions in a liquid crystalline (LC) medium (triton X-100/water).
      Films prepared in water and in the absence of template were used for control
      studies. Infrared spectroscopic studies demonstrated comparable chemical
      compositions for LC and control polymer films. SEM studies revealed that the
      topologies of the molecularly imprinted polymer films prepared in the LC medium
      (LC-MIP) exhibit discernible 40 nm thick nano-fiber structures, quite unlike the
      polymers prepared in the absence of the LC-phase. The sensitivity of the LC-MIP
      in a quartz crystal microbalance (QCM) sensor platform was 67.6 +/- 4.9 Hz/mM
      under flow injection analysis (FIA) conditions, which was ~250% higher than for
      the sensor prepared using the aqueous medium. Detection was possible at 100 nM
      (30 ng/mL), and discrimination of bupivacaine from closely related structural
      analogs was readily achieved as reflected in the corresponding stability
      constants of the MIP-analyte complexes. The facile fabrication and significant
      enhancement in sensor sensitivity together highlight the potential of this LC
      based imprinting strategy for fabrication of polymeric materials with
      hierarchical architectures, in particular for use in surface-dependent
      application areas, e.g., biomaterials or sensing. 

PMID- 25587414
TI  - A phage display screening derived Peptide with affinity for the adeninyl moiety.
AB  - Phage display screening of a surface-immobilized adenine derivative led to the
      identification of a heptameric peptide with selectivity for adenine as
      demonstrated through quartz crystal microbalance (QCM) studies. The peptide
      demonstrated a concentration dependent affinity for an adeninyl moiety decorated
      surface (K D of 968 +/- 53.3 MUM), which highlights the power of piezoelectric
      sensing in the study of weak interactions. 

PMID- 25587415
TI  - Use of a parasitic wasp as a biosensor.
AB  - Screening cargo for illicit substances is in need of rapid high-throughput
      inspection systems that accurately identify suspicious cargo. Here we investigate
      the ability of a parasitic wasp, Microplitis croceipes to detect and respond to
      methyl benzoate, the volatile component of cocaine, by examining their response
      to training concentrations, their sensitivity at low concentrations, and their
      ability to detect methyl benzoate when two concealment substances (green tea and
      ground coffee) are added to the testing arena. Utilizing classical associative
      learning techniques with sucrose as reward, we found that M. croceipes learns
      individual concentrations of methyl benzoate, and they can generalize this
      learning to concentrations 100* lower than the training concentration. Their
      sensitivity to methyl benzoate is very low at an estimated 3 ppb. They are also
      able to detect methyl benzoate when covered completely by green tea, but were not
      able to detect methyl benzoate when covered completely by coffee grounds.
      Habituation to the tea and coffee odors prior to testing improves their
      responses, resulting in effective detection of methyl benzoate covered by the
      coffee grounds. With the aid of the portable device called 'the wasp hound', the
      wasps appear to have potential to be effective on-site biosensors for the
      detection of cocaine. 

PMID- 25587416
TI  - Polymerization Parameters Influencing the QCM Response Characteristics of BSA
      MIP.
AB  - Designing Molecularly Imprinted Polymers for sensing proteins is still a somewhat
      empirical process due to the inherent complexity of protein imprinting. Based on
      Bovine Serum Albumin as a model analyte, we explored the influence of a range of
      experimental parameters on the final sensor responses. The optimized polymer
      contains 70% cross linker. Lower amounts lead to higher sensitivity, but also
      sensor response times substantially increase (to up to 10 h) at constant
      imprinting effect (signal ratio MIP/NIP on quartz crystal microbalance-QCM).
      However, by shifting the polymer properties to more hydrophilic by replacing
      methacrylic acid by acrylic acid, part of the decreased sensitivity can be
      recovered leading to appreciable sensor responses. Changing polymer morphology by
      bulk imprinting and nanoparticle approaches has much lower influence on
      sensitivity. 

PMID- 25587413
TI  - Recent advances in bioprinting and applications for biosensing.
AB  - Future biosensing applications will require high performance, including real-time
      monitoring of physiological events, incorporation of biosensors into feedback
      based devices, detection of toxins, and advanced diagnostics. Such functionality
      will necessitate biosensors with increased sensitivity, specificity, and
      throughput, as well as the ability to simultaneously detect multiple analytes.
      While these demands have yet to be fully realized, recent advances in
      biofabrication may allow sensors to achieve the high spatial sensitivity
      required, and bring us closer to achieving devices with these capabilities. To
      this end, we review recent advances in biofabrication techniques that may enable
      cutting-edge biosensors. In particular, we focus on bioprinting techniques (e.g.,
      microcontact printing, inkjet printing, and laser direct-write) that may prove
      pivotal to biosensor fabrication and scaling. Recent biosensors have employed
      these fabrication techniques with success, and further development may enable
      higher performance, including multiplexing multiple analytes or cell types within
      a single biosensor. We also review recent advances in 3D bioprinting, and explore
      their potential to create biosensors with live cells encapsulated in 3D
      microenvironments. Such advances in biofabrication will expand biosensor utility
      and availability, with impact realized in many interdisciplinary fields, as well
      as in the clinic. 

PMID- 25587418
TI  - Magnetic Properties of FeNi-Based Thin Film Materials with Different Additives.
AB  - This paper presents a study of FeNi-based thin film materials deposited with Mo,
      Al and B using a co-sputtering process. The existence of soft magnetic properties
      in combination with strong magneto-mechanical coupling makes these materials
      attractive for sensor applications. Our findings show that FeNi deposited with Mo
      or Al yields magnetically soft materials and that depositing with B further
      increases the softness. The out-of-plane magnetic anisotropy of FeNi thin films
      is reduced by depositing with Al and completely removed by depositing with B. The
      effect of depositing with Mo is dependent on the Mo concentration. The coercivity
      of FeNiMo and FeNiAl is reduced to less than a half of that of FeNi, and a value
      as low as 40 A/m is obtained for FeNiB. The surfaces of the obtained FeNiMo,
      FeNiAl and FeNiB thin films reveal very different morphologies. The surface of
      FeNiMo shows nano-cracks, while the FeNiAl films show large clusters and fewer
      nano-cracks. When FeNi is deposited with B, a very smooth morphology is obtained.
      The crystal structure of FeNiMo strongly depends on the depositant concentration
      and changes into an amorphous structure at a higher Mo level. FeNiAl thin films
      remain polycrystalline, even at a very high concentration of Al, and FeNiB films
      are amorphous, even at a very low concentration of B. 

PMID- 25587417
TI  - Localized surface plasmon resonance as a biosensing platform for developing
      countries.
AB  - The discovery of the phenomena known as localized surface plasmon resonance
      (LSPR) has provided the basis for many research areas, ranging from materials
      science to biosensing. LSPR has since been viewed as a transduction platform that
      could yield affordable, portable devices for a multitude of applications. This
      review aims to outline the potential applications within developing countries and
      the challenges that are likely to be faced before the technology can be
      effectively employed. 

PMID- 25587419
TI  - An inexpensive, fast and sensitive quantitative lateral flow magneto-immunoassay
      for total prostate specific antigen.
AB  - We describe the detection characteristics of a device the Resonant Coil
      Magnetometer (RCM) to quantify paramagnetic particles (PMPs) in
      immunochromatographic (lateral flow) assays. Lateral flow assays were developed
      using PMPs for the measurement of total prostate specific antigen (PSA) in serum
      samples. A detection limit of 0.8 ng/mL was achieved for total PSA using the RCM
      and is at clinically significant concentrations. Comparison of data obtained in a
      pilot study from the analysis of serum samples with commercially available
      immunoassays shows good agreement. The development of a quantitative magneto
      immunoassay in lateral flow format for total PSA suggests the potential of the
      RCM to operate with many immunoassay formats. The RCM has the potential to be
      modified to quantify multiple analytes in this format. This research shows
      promise for the development of an inexpensive device capable of quantifying
      multiple analytes at the point-of-care using a magneto-immunoassay in lateral
      flow format. 

PMID- 25587421
TI  - Electrochemical biosensors based on ferroceneboronic Acid and its derivatives: a
      review.
AB  - We review recent progress in the development of electrochemical biosensors based
      on ferroceneboronic acid (FcBA) and ferrocene (Fc)-modified boronic acids. These
      compounds can be used to construct electrochemical biosensors because they
      consist of a binding site (i.e., a boronic acid moiety) and an electrochemically
      active part (i.e., an Fc residue). By taking advantage of the unique properties
      of FcBA and its derivatives, electrochemical sensors sensitive to sugars,
      glycated hemoglobin (HbA1c), fluoride (F(-)) ions, and so forth have been widely
      studied. FcBA-based sugar sensors rely on the selective binding of FcBA to 1,2-
      or 1,3-diol residues of sugars through the formation of cyclic boronate ester
      bonds. The redox properties of FcBA-sugar adduct differ from those of free FcBA,
      which forms the basis of the electrochemical determination of sugars. Thus, non
      enzymatic glucose sensors are now being actively studied using FcBA and Fc
      modified boronic acids as redox markers. Using a similar principle, HbA1c can be
      detected by FcBA-based electrochemical systems because it contains hydrocarbon
      chains on the polypeptide chain. HbA1c sensors are useful for monitoring blood
      glucose levels over the preceding 8-12 weeks. In addition, FcBA and Fc-modified
      boronic acids have been used for the detection of F(-) ions due to the selective
      binding of boronic acid to F(-) ions. F(-)-ion sensors may be useful alternatives
      to conventional ion-selective electrodes sensitive to F(-) ion. Furthermore, FcBA
      derivatives have been studied to construct lectin; steroids; nucleotides;
      salicylic acid; and bacteria sensors. One of the limitations of FcBA-based
      sensors comes from the fact that FcBA derivatives are added in sample solutions
      as reagents. FcBA derivatives should be immobilized on the surface of electrodes
      for developing reagentless sensors. 

PMID- 25587422
TI  - Study of Paclitaxel-Treated HeLa Cells by Differential Electrical Impedance Flow
      Cytometry.
AB  - This work describes the electrical investigation of paclitaxel-treated HeLa cells
      using a custom-made microfluidic biosensor for whole cell analysis in continuous
      flow. We apply the method of differential electrical impedance spectroscopy to
      treated HeLa cells in order to elucidate the changes in electrical properties
      compared with non-treated cells. We found that our microfluidic system was able
      to distinguish between treated and non-treated cells. Furthermore, we utilize a
      model for electrical impedance spectroscopy in order to perform a theoretical
      study to clarify our results. This study focuses on investigating the changes in
      the electrical properties of the cell membrane caused by the effect of
      paclitaxel. We observe good agreement between the model and the obtained results.
      This establishes the proof-of-concept for the application in cell drug therapy. 

PMID- 25587420
TI  - Sensing magnetic directions in birds: radical pair processes involving
      cryptochrome.
AB  - Birds can use the geomagnetic field for compass orientation. Behavioral
      experiments, mostly with migrating passerines, revealed three characteristics of
      the avian magnetic compass: (1) it works spontaneously only in a narrow
      functional window around the intensity of the ambient magnetic field, but can
      adapt to other intensities, (2) it is an "inclination compass", not based on the
      polarity of the magnetic field, but the axial course of the field lines, and (3)
      it requires short-wavelength light from UV to 565 nm Green. The Radical Pair
      Model of magnetoreception can explain these properties by proposing spin-chemical
      processes in photopigments as underlying mechanism. Applying radio frequency
      fields, a diagnostic tool for radical pair processes, supports an involvement of
      a radical pair mechanism in avian magnetoreception: added to the geomagnetic
      field, they disrupted orientation, presumably by interfering with the receptive
      processes. Cryptochromes have been suggested as receptor molecules. Cry1a is
      found in the eyes of birds, where it is located at the membranes of the disks in
      the outer segments of the UV-cones in chickens and robins. Immuno-histochemical
      studies show that it is activated by the wavelengths of light that allow magnetic
      compass orientation in birds. 

PMID- 25587424
TI  - Piezoelectric biosensors for organophosphate and carbamate pesticides: a review.
AB  - Due to the great amount of pesticides currently being used, there is an increased
      interest for developing biosensors for their detection. Among all the physical
      transducers, piezoelectric systems have emerged as the most attractive due to
      their simplicity, low instrumentation costs, possibility for real-time and label
      free detection and generally high sensitivity. This paper presents an overview of
      biosensors based on the quartz crystal microbalance, which have been reported in
      the literature for organophosphate and carbamate pesticide analysis. 

PMID- 25587423
TI  - Biosensors with built-in biomolecular logic gates for practical applications.
AB  - Molecular logic gates, designs constructed with biological and chemical
      molecules, have emerged as an alternative computing approach to silicon-based
      logic operations. These molecular computers are capable of receiving and
      integrating multiple stimuli of biochemical significance to generate a definitive
      output, opening a new research avenue to advanced diagnostics and therapeutics
      which demand handling of complex factors and precise control. In molecularly
      gated devices, Boolean logic computations can be activated by specific inputs and
      accurately processed via bio-recognition, bio-catalysis, and selective chemical
      reactions. In this review, we survey recent advances of the molecular logic
      approaches to practical applications of biosensors, including designs constructed
      with proteins, enzymes, nucleic acids, nanomaterials, and organic compounds, as
      well as the research avenues for future development of digitally operating "sense
      and act" schemes that logically process biochemical signals through networked
      circuits to implement intelligent control systems. 

PMID- 25587425
TI  - Microelectrode Arrays and the Use of PEG-Functionalized Diblock Copolymer
      Coatings.
AB  - PEG-modified diblock copolymer surfaces have been examined for their
      compatibility with microelectrode array based analytical methods. The use of PEG
      modified polymer surfaces on the arrays was initially problematic because the
      redox couples used in the experiments were adsorbed by the polymer. This led the
      current measured by cyclic voltammetry for the redox couple to be unstable and
      increase with time. However, two key findings allow the experiments to be
      successful. First, after multiple cyclic voltammograms the current associated
      with the redox couple does stabilize so that a good baseline current can be
      established. Second, the rate at which the current stabilizes is consistent every
      time a particular coated array is used. Hence, multiple analytical experiments
      can be conducted on an array coated with a PEG-modified diblock copolymer and the
      data obtained is comparable as long as the data for each experiment is collected
      at a consistent time point. 

PMID- 25587426
TI  - Biosensor Applications of MAPLE Deposited Lipase.
AB  - Matrix Assisted Pulsed Laser Evaporation (MAPLE) is a thin film deposition
      technique derived from Pulsed Laser Deposition (PLD) for deposition of delicate
      (polymers, complex biological molecules, etc.) materials in undamaged form. The
      main difference of MAPLE technique with respect to PLD is the target: it is a
      frozen solution or suspension of the (guest) molecules to be deposited in a
      volatile substance (matrix). Since laser beam energy is mainly absorbed by the
      matrix, damages to the delicate guest molecules are avoided, or at least reduced.
      Lipase, an enzyme catalyzing reactions borne by triglycerides, has been used in
      biosensors for detection of beta-hydroxyacid esters and triglycerides in blood
      serum. Enzymes immobilization on a substrate is therefore required. In this paper
      we show that it is possible, using MAPLE technique, to deposit lipase on a
      substrate, as shown by AFM observation, preserving its conformational structure,
      as shown by FTIR analysis. 

PMID- 25587427
TI  - Detection of the inflammation biomarker C-reactive protein in serum samples:
      towards an optimal biosensor formula.
AB  - The development of an electrochemical immunosensor for the biomarker, C-reactive
      protein (CRP), is reported in this work. CRP has been used to assess inflammation
      and is also used in a multi-biomarker system as a predictive biomarker for
      cardiovascular disease risk. A gold-based working electrode sensor was developed,
      and the types of electrode printing inks and ink curing techniques were then
      optimized. The electrodes with the best performance parameters were then employed
      for the construction of an immunosensor for CRP by immobilizing anti-human CRP
      antibody on the working electrode surface. A sandwich enzyme-linked immunosorbent
      assay (ELISA) was then constructed after sample addition by using anti-human CRP
      antibody labelled with horseradish peroxidase (HRP). The signal was generated by
      the addition of a mediator/substrate system comprised of 3,3,5',5'
      Tetramethylbenzidine dihydrochloride (TMB) and hydrogen peroxide (H2O2).
      Measurements were conducted using chronoamperometry at -200 mV against an
      integrated Ag/AgCl reference electrode. A CRP limit of detection (LOD) of 2.2
      ng.mL(-1) was achieved in spiked serum samples, and performance agreement was
      obtained with reference to a commercial ELISA kit. The developed CRP immunosensor
      was able to detect a diagnostically relevant range of the biomarker in serum
      without the need for signal amplification using nanoparticles, paving the way for
      future development on a cardiac panel electrochemical point-of-care diagnostic
      device. 

PMID- 25587428
TI  - Evaluating the Equilibrium Association Constant between ArtinM Lectin and Myeloid
      Leukemia Cells by Impedimetric and Piezoelectric Label Free Approaches.
AB  - Label-free methods for evaluating lectin-cell binding have been developed to
      determine the lectin-carbohydrate interactions in the context of cell-surface
      oligosaccharides. In the present study, mass loading and electrochemical
      transducer signals were compared to characterize the interaction between lectin
      and cellular membranes by measuring the equilibrium association constant, Ka ,
      between ArtinM lectin and the carbohydrate sites of NB4 leukemia cells. By
      functionalizing sensor interfaces with ArtinM, it was possible to determine Ka
      over a range of leukemia cell concentrations to construct analytical curves from
      impedimetric and/or mass-associated frequency shifts with analytical signals
      following a Langmuir pattern. Using the Langmuir isotherm-binding model, the Ka
      obtained were (8.9 +/- 1.0) * 10(-5) mL/cell and (1.05 +/- 0.09) * 10(-6) mL/cell
      with the electrochemical impedance spectroscopy (EIS) and quartz crystal
      microbalance (QCM) methods, respectively. The observed differences were
      attributed to the intrinsic characteristic sensitivity of each method in
      following Langmuir isotherm premises. 

PMID- 25587429
TI  - Carboxylated or aminated polyaniline-multiwalled carbon nanotubes nanohybrids for
      immobilization of cellobiose dehydrogenase on gold electrodes.
AB  - Polymer-multiwalled carbon nanotube (MWCNT) nanohybrids, which differ in surface
      charge have been synthesized to study the bioelectrocatalysis of adsorbed
      cellobiose dehydrogenase (CDH) from Phanerochaete sordida on gold electrodes. To
      obtain negatively charged nanohybrids, poly(3-amino-4-methoxybenzoic acid-co
      aniline) (P(AMB-A)) was covalently linked to the surface of MWCNTs while
      modification with p-phenylenediamine (PDA) converted the COOH-groups to
      positively charged amino groups. Fourier transform infrared spectroscopy (FTIR)
      measurements verified the p-phenylenediamine (PDA) modification of the polymer
      CNT nanohybrids. The positively charged nanohybrid MWCNT-P(AMB-A)-PDA promoted
      direct electron transfer (DET) of CDH to the electrode and bioelectrocatalysis of
      lactose was observed. Amperometric measurements gave an electrochemical response
      with KMapp = 8.89 mM and a current density of 410 nA/cm(2) (15 mM lactose). The
      catalytic response was tested at pH 3.5 and 4.5. Interference by ascorbic acid
      was not observed. The study proves that DET between the MWCNT-P(AMB-A)-PDA
      nanohybrids and CDH is efficient and allows the sensorial detection of lactose. 

PMID- 25587430
TI  - Development of a Pseudomonas aeruginosa Agmatine Biosensor.
AB  - Agmatine, decarboxylated arginine, is an important intermediary in polyamine
      production for many prokaryotes, but serves higher functions in eukaryotes such
      as nitric oxide inhibition and roles in neurotransmission. Pseudomonas aeruginosa
      relies on the arginine decarboxylase and agmatine deiminase pathways to convert
      arginine into putrescine. One of the two known agmatine deiminase operons, aguBA,
      contains an agmatine sensitive TetR promoter controlled by AguR. We have
      discovered that this promoter element can produce a titratable induction of its
      gene products in response to agmatine, and utilized this discovery to make a
      luminescent agmatine biosensor in P. aeruginosa. The genome of the P. aeruginosa
      lab strain UCBPP-PA14 was altered to remove both its ability to synthesize or
      destroy agmatine, and insertion of the luminescent reporter construct allows it
      to produce light in proportion to the amount of exogenous agmatine applied from
      ~100 nM to 1mM. Furthermore it does not respond to related compounds including
      arginine or putrescine. To demonstrate potential applications the biosensor was
      used to detect agmatine in spent supernatants, to monitor the development of
      arginine decarboxylase over time, and to detect agmatine in the spinal cords of
      live mice. 

PMID- 25587431
TI  - Electrical Wiring of the Aldehyde Oxidoreductase PaoABC with a Polymer Containing
      Osmium Redox Centers: Biosensors for Benzaldehyde and GABA.
AB  - Biosensors for the detection of benzaldehyde and gamma-aminobutyric acid (GABA)
      are reported using aldehyde oxidoreductase PaoABC from Escherichia coli
      immobilized in a polymer containing bound low potential osmium redox complexes.
      The electrically connected enzyme already electrooxidizes benzaldehyde at
      potentials below -0.15 V (vs. Ag|AgCl, 1 M KCl). The pH-dependence of
      benzaldehyde oxidation can be strongly influenced by the ionic strength. The
      effect is similar with the soluble osmium redox complex and therefore indicates a
      clear electrostatic effect on the bioelectrocatalytic efficiency of PaoABC in the
      osmium containing redox polymer. At lower ionic strength, the pH-optimum is high
      and can be switched to low pH-values at high ionic strength. This offers
      biosensing at high and low pH-values. A "reagentless" biosensor has been formed
      with enzyme wired onto a screen-printed electrode in a flow cell device. The
      response time to addition of benzaldehyde is 30 s, and the measuring range is
      between 10-150 uM and the detection limit of 5 uM (signal to noise ratio 3:1) of
      benzaldehyde. The relative standard deviation in a series (n = 13) for 200 uM
      benzaldehyde is 1.9%. For the biosensor, a response to succinic semialdehyde was
      also identified. Based on this response and the ability to work at high pH a
      biosensor for GABA is proposed by coimmobilizing GABA-aminotransferase (GABA-T)
      and PaoABC in the osmium containing redox polymer. 

PMID- 25587432
TI  - Microfabricated tactile sensors for biomedical applications: a review.
AB  - During the last decades, tactile sensors based on different sensing principles
      have been developed due to the growing interest in robotics and, mainly, in
      medical applications. Several technological solutions have been employed to
      design tactile sensors; in particular, solutions based on microfabrication
      present several attractive features. Microfabrication technologies allow for
      developing miniaturized sensors with good performance in terms of metrological
      properties (e.g., accuracy, sensitivity, low power consumption, and frequency
      response). Small size and good metrological properties heighten the potential
      role of tactile sensors in medicine, making them especially attractive to be
      integrated in smart interfaces and microsurgical tools. This paper provides an
      overview of microfabricated tactile sensors, focusing on the mean principles of
      sensing, i.e., piezoresistive, piezoelectric and capacitive sensors. These
      sensors are employed for measuring contact properties, in particular force and
      pressure, in three main medical fields, i.e., prosthetics and artificial skin,
      minimal access surgery and smart interfaces for biomechanical analysis. The
      working principles and the metrological properties of the most promising tactile,
      microfabricated sensors are analyzed, together with their application in
      medicine. Finally, the new emerging technologies in these fields are briefly
      described. 

PMID- 25587433
TI  - Fabrication of functionalized carbon nanotube buckypaper electrodes for
      application in glucose biosensors.
AB  - A highly sensitive glucose detection method was developed using functionalized
      carbon nanotube buckypaper as a free standing electrode in an electrochemical
      biosensor. Glucose oxidase was immobilized onto various buckypaper samples in
      order to oxidize glucose resulting in a measureable current/voltage signal output
      of the biosensor. Cyclic voltammetry (CV) and amperometry were utilized to
      determine the sensitivity of these buckypaper electrodes. Sensors of three
      different types of buckypaper were prepared and compared. These modified
      buckypaper electrode-based sensors showed much higher sensitivity to glucose
      compared to other electrochemical glucose sensors. 

PMID- 25587434
TI  - Trimetallic (aurod-pdshell-ptcluster) catalyst used as amperometric hydrogen
      peroxide sensor.
AB  - Bimetallic nanostructured core-shell structures are commonly used as catalysts in
      a wide variety of reactions. We surmised that the addition of an additional metal
      would potentially allow catalytic tailoring with the possibility of an increase
      in activity. Here a tri-metallic catalytic structure, consisting of clustered
      catalytic Pt on the surface of a Pd shell supported on a rod shaped Au core was
      fabricated. The significance of the additional metallic component is shown by
      comparative electrochemically active surface area (ECSA) analysis results for the
      trimetallic Aurod-Pdshell-Ptcluster, bimetallic Aurod-Ptcluster and monometallic
      JM-Pt (used as a reference), which have respective ECSA values (cm(2)/mgPt) of
      1883.0, 1371.7 and 879. The potential utility of the trimetallic catalysts was
      shown in a hydrogen peroxide sensing protocol, which showed the catalyst to have
      a sensitivity of 604 iA/mMcm(2) within a linear range of 0.0013-6.191 mM. 

PMID- 25587435
TI  - Biosensors for the detection of antibiotics in poultry industry-a review.
AB  - Antibiotic resistance is emerging as a potential threat in the next decades. This
      is a global phenomenon whereby globalization is acting as a catalyst. Presently,
      the most common techniques used for the detection of antibiotics are biosensors,
      ELISA and liquid chromatography-mass spectrometry. Each of these techniques has
      its benefits as well as drawbacks. This review aims to evaluate different
      biosensing techniques and their working principles in order to accurately,
      quickly and practically detect antibiotics in chicken muscle and blood serum. The
      review is divided into three main sections, namely: a biosensors overview, a
      section on biosensor recognition and a section on biosensor transducing elements.
      The first segment provides a detailed overview on the different techniques
      available and their respective advantages and disadvantages. The second section
      consists of an evaluation of several analyte systems and their mechanisms. The
      last section of this review studies the working principles of biosensing
      transducing elements, focusing mainly on surface plasmon resonance (SPR)
      technology and its applications in industries. 

PMID- 25587437
TI  - High-contrast fluorescence microscopy for a biomolecular analysis based on
      polarization techniques using an optical interference mirror slide.
AB  - Fluorescence microscopy with an improved contrast for fluorescence images is
      developed using an optical interference mirror (OIM) slide, which can enhance the
      fluorescence from a fluorophore as a result of the double interference of the
      excitation light and emission light. To improve the contrast of a fluorescence
      image using an OIM slide, a linearly-polarized excitation light was employed, and
      the fluorescence emission polarized perpendicular to the polarization of the
      excitation light was detected. The image contrast with this optical system was
      improved 110-fold for rhodamine B spotted on the OIM, in comparison with a glass
      slide using a general fluorescence microscopy optical system. Moreover, a 24-fold
      improvement of the image contrast was achieved for the detection of Cy3-labeled
      streptavidin bound to immobilize biotin. 

PMID- 25587436
TI  - Biosensors for inorganic and organic arsenicals.
AB  - Arsenic is a natural environmental contaminant to which humans are routinely
      exposed and is strongly associated with human health problems, including cancer,
      cardiovascular and neurological diseases. To date, a number of biosensors for the
      detection of arsenic involving the coupling of biological engineering and
      electrochemical techniques has been developed. The properties of whole-cell
      bacterial or cell-free biosensors are summarized in the present review with
      emphasis on their sensitivity and selectivity. Their limitations and future
      challenges are highlighted. 

PMID- 25587439
TI  - Mucocutaneous Manifestations of HIV and the Correlation with WHO Clinical Staging
      in a Tertiary Hospital in Nigeria.
AB  - Skin diseases are indicators of HIV/AIDS which correlates with WHO clinical
      stages. In resource limited environment where CD4 count is not readily available,
      they can be used in assessing HIV patients. The study aims to determine the
      mucocutaneous manifestations in HIV positive patients and their correlation with
      WHO clinical stages. A prospective cross-sectional study of mucocutaneous
      conditions was done among 215 newly diagnosed HIV patients from June 2008 to May
      2012 at adult ART clinic, Wesley Guild Hospital Unit, OAU Teaching Hospitals
      Complex, Ilesha, Osun State, Nigeria. There were 156 dermatoses with
      oral/oesophageal/vaginal candidiasis (41.1%), PPE (24.4%), dermatophytic
      infections (8.9%), and herpes zoster (3.8%) as the most common dermatoses. The
      proportions of dermatoses were 4.5%, 21.8%, 53.2%, and 20.5% in stages 1-4,
      respectively. A significant relationship (using Pearson's Chi square with P value
      <0.05) was obtained between dermatoses and WHO clinical stages. Pearson's
      correlation coefficient showed a positive correlation between the number of
      dermatoses and the WHO clinical stages. Dermatoses can therefore serve as
      diagnostic and prognostic markers in resource limited settings to initiate HAART
      in clinical stages 3 and 4. 

PMID- 25587438
TI  - A delphi study to detect deficiencies and propose actions in real life treatment
      of neovascular age-related macular degeneration.
AB  - Purpose. Spanish retina specialists were surveyed in order to propose actions to
      decrease deficiencies in real-life neovascular age macular degeneration treatment
      (nv-AMD). Methods. One hundred experts, members of the Spanish Vitreoretinal
      Society (SERV), were invited to complete an online survey of 52 statements about
      nv-AMD management with a modified Delphi methodology. Four rounds were performed
      using a 5-point Linkert scale. Recommendations were developed after analyzing the
      differences between the results and the SERV guidelines recommendations. Results.
      Eighty-seven specialists completed all the Delphi rounds. Once major potential
      deficiencies in real-life nv-AMD treatment were identified, 15 recommendations
      were developed with a high level of agreement. Consensus statements to reduce the
      burden of the disease included the use of treat and extend regimen and to reduce
      the amount of diagnostic tests during the loading phase and training technical
      staff to perform these tests and reduce the time between relapse detection and
      reinjection, as well as establishing patient referral protocols to outside
      general ophthalmology clinics. Conclusion. The level of agreement with the final
      recommendations for nv-AMD treatment among Spanish retinal specialist was high
      indicating that some actions could be applied in order to reduce the deficiencies
      in real-life nv-AMD treatment. 

PMID- 25587440
TI  - A retrospective study investigating the incidence and predisposing factors of
      hospital-acquired anemia.
AB  - Hospitalized patients frequently have considerable volumes of blood removed for
      diagnostic testing which could lead to the development of hospital-acquired
      anemia. Low hemoglobin levels during hospitalization may result in significant
      morbidity for patients with underlying cardiorespiratory and other illnesses. We
      performed a retrospective study and data was collected using a chart review
      facilitated through an electronic medical record. A total of 479 patients who
      were not anemic during admission were included in analysis. In our study, we
      investigated the incidence of HAA and found that, between admission and
      discharge, 65% of patients dropped their hemoglobin by 1.0 g/dL or more, and 49%
      of patients developed anemia. We also found that the decrease in hemoglobin
      between admission and discharge did not differ significantly with smaller
      phlebotomy tubes. In multivariate analysis, we found that patients with longer
      hospitalization and those with lower BMI are at higher risk of developing HAA. In
      conclusion, our study confirms that hospital-acquired anemia is common. More
      aggressive strategies such as reducing the frequency of blood draws and expanding
      the use of smaller volume tubes for other laboratory panels may be helpful in
      reducing the incidence of HAA during hospitalization. 

PMID- 25587441
TI  - Freedom and confinement: patients' experiences of life with home haemodialysis.
AB  - Patients with chronic end stage renal disease need dialysis to survive; however,
      they also need a treatment that suits their life situation. It is important that
      healthcare providers provide reliable, up-to-date information about different
      dialysis treatment options. Since home haemodialysis is a relatively new
      treatment, it is necessary to gather more knowledge about what the treatment
      entails from the patient's perspective. The aim of this study was to describe
      patients' experiences of having home haemodialysis. To gain access to the
      patients' experiences, they were asked to write narratives, which describe both
      their good and bad experiences of life with the treatment. The narratives were
      analysed with a qualitative method. The results of this analysis are subdivided
      into five themes: freedom to be at home and control their own treatment, feeling
      of being alone with the responsibility, changes in the home environment, need for
      support, and security and well-being with home haemodialysis. The conclusion is
      that home haemodialysis provides a certain level of freedom, but the freedom is
      limited as the treatment itself is restrictive. In order to improve patients'
      experiences with home haemodialysis, more research based on patients' experiences
      is needed and it is necessary to involve the patients in the development of the
      care. 

PMID- 25587442
TI  - Surgical implications of asymmetric distribution of dermal collagen and elastic
      fibres in two orientations of skin samples from extremities.
AB  - Background. Clinically, scar related complications are observed to be dissimilar
      in different regions of the body. Unequal distribution of dermal collagen and
      elastic fibres in different orientations could be one of the multifocal causes of
      scar related complications, for which this evaluating study has been taken up.
      Materials and Method. 300 skin samples collected in horizontal and vertical
      orientations were studied histomorphometrically. This study involved image
      analysis of specially stained histological section using tissue-quant software.
      The outcome result was termed as quantitative fraction. From the result, various
      ratio values were also calculated for the ratio analysis. Results. The
      differences in the quantitative fraction of dermal elastic content between 2
      directions were statistically significant at joint areas (shoulder joint, wrist,
      and ankle) (P < 0.001) but for collagen, significant difference was observed at
      shoulder joint and wrist only. Dermis of the forearm and thigh did not show any
      differences in their collagen content, but for elastic, thigh did show a
      significant difference while forearm had no change between 2 directions.
      Conclusion. Analysis of unequal content of dermal element in two directions under
      the perspective of wound healing consequences is subjective depending upon the
      anatomical position and functional status of the areas. 

PMID- 25587444
TI  - Premature calcifications of costal cartilages: a new perspective.
AB  - Background. Calcifications of the costal cartilages occur, as a rule, not until
      the age of 30 years. The knowledge of the clinical significance of early and
      extensive calcifications is still incomplete. Materials and Methods. A search was
      made to find patients below the age of 30 years who showed distinct
      calcifications of their lower costal cartilages by viewing 360 random samples of
      intravenous pyelograms and abdominal plain films. The histories, and clinical and
      laboratory findings of these patients were analyzed. Results. Nineteen patients
      fulfilled the criteria of premature calcifications of costal cartilages (CCCs).
      The patients had in common that they were frequently referred to a hospital and
      were treated by several medical disciplines. Nevertheless many complaints of the
      patients remained unsolved. Premature CCCs were often associated with rare
      endocrine disorders, inborn errors of metabolism, and abnormal hematologic
      findings. Among the metabolic disorders there were 2 proven porphyrias and 7
      patients with a suspected porphyria but with inconclusive laboratory findings.
      Conclusion. Premature CCCs are unlikely to be a normal variant in skeletal
      radiology. The findings in this small group of patients call for more intensive
      studies, especially in regard to the putative role of a porphyria. 

PMID- 25587443
TI  - Sleep disordered breathing in children with mitochondrial disease.
AB  - A retrospective chart review study was performed to determine the presence of
      sleep disordered breathing (SDB) in children with primary mitochondrial disease
      (MD). The symptoms, sleep-related breathing, and movement abnormalities are
      described for 18 subjects (ages 1.5 to 18 years, 61% male) with MD who underwent
      polysomnography in our pediatric sleep center from 2007 to 2012. Of the 18
      subjects with MD, the common indications for polysomnography were excessive
      somnolence or fatigue (61%, N = 11), snoring (44%, N = 8), and sleep movement
      complaints (17%, N = 3). Polysomnographic measurements showed SDB in 56% (N = 10)
      (obstructive sleep apnea in 60% (N = 6), hypoxemia in 40% (N = 4), and sleep
      hypoventilation in 20% (N = 2)). There was a significant association between
      decreased muscle tone and SDB (P: 0.043) as well as obese and overweight status
      with SDB (P = 0.036). SDB is common in subjects with MD. Early detection of SDB,
      utilizing polysomnography, should be considered to assist in identification of MD
      patients who may benefit from sleep-related interventions. 

PMID- 25587445
TI  - Image guidance in radiation therapy: techniques and applications.
AB  - In modern day radiotherapy, the emphasis on reduction on volume exposed to high
      radiotherapy doses, improving treatment precision as well as reducing radiation
      related normal tissue toxicity has increased, and thus there is greater
      importance given to accurate position verification and correction before
      delivering radiotherapy. At present, several techniques that accomplish these
      goals impeccably have been developed, though all of them have their limitations.
      There is no single method available that eliminates treatment-related
      uncertainties without considerably adding to the cost. However, delivering "high
      precision radiotherapy" without periodic image guidance would do more harm than
      treating large volumes to compensate for setup errors. In the present review, we
      discuss the concept of image guidance in radiotherapy, the current techniques
      available, and their expected benefits and pitfalls. 

PMID- 25587446
TI  - Passive Posterior Tibial Subluxation on Routine Knee MRI as a Secondary Sign of
      PCL Tear.
AB  - The posterior drawer test is an accurate clinical test to diagnose posterior
      cruciate ligament (PCL), indicating laxity of the PCL that allows posterior
      tibial translation. This study aimed to determine whether posterior tibial
      translation relative to the femur on routine MRI could serve as an additional
      sign of PCL tear. Routine knee MRI in eleven patients (7 males, 4 females) with
      arthroscopically confirmed isolated PCL tears were reviewed independently by two
      musculoskeletal radiologists. Measurements of tibial translation were made in the
      medial and lateral compartments of patients and controls (10 males, 12 females)
      without clinical or MRI evidence of ligament injury. Significant medial
      compartment posterior tibial translation was present in patients with PCL tear
      compared to controls (+2.93 mm versus +0.03 mm, P = 0.002) with excellent
      interobserver agreement (intraclass correlation coefficient (ICC) = 0.94). No
      significant difference in lateral compartment tibial translation was observed
      (+0.17 mm versus -0.57 mm, P = 0.366) despite excellent interobserver agreement
      (ICC = 0.96). Posterior tibial translation in the midmedial compartment may be a
      secondary sign of isolated PCL tear on routine knee MRI with passive extension
      without manipulation or weight bearing. Additional work in a larger cohort may
      better address the accuracy of this finding. 

PMID- 25587447
TI  - Annual decline in pentraxin 3 is a risk of vascular access troubles in
      hemodialysis patients.
AB  - Pentraxin 3 (PTX3), a multifunctional modulator of the innate immunoinflammatory
      response, is higher in patients undergoing hemodialysis than healthy control. Our
      study focused on annual change in PTX3 levels in patients with chronic
      hemodialysis, because regularly undergoing hemodialysis for many years modifies
      vascular inflammatory status. To demonstrate whether annual change in PTX3 is
      associated with vascular events, we measured blood levels of pentraxins (PTX3 and
      high-sensitivity C-reactive protein (hsCRP)) at baseline and in the next year in
      76 hemodialysis patients and observed 20 patients with vascular access troubles
      during follow-up years. The annual decline in PTX3, but not hsCRP, is a
      significant risk of the incidence of vascular access trouble that is a critical
      and specific complication for hemodialysis patients (hazard ratio; 0.732 per +1
      ng/mL/year in PTX3, (*) P = 0.039). This study is the first to focus on the
      annual change of pentraxins in a hemodialysis cohort. 

PMID- 25587448
TI  - Sustainability literacy of older people in retirement villages.
AB  - With many developed countries experiencing the aging of the population, older
      people play a large role in contributing to environmental problems but also to
      environmental solutions. The purpose of this research is to understand the
      awareness and behavior of current older people living in retirement villages
      towards sustainability development. To achieve this, a sustainability literacy
      survey was conducted with 65 older residents of a private retirement village
      located 10 Km outside the Brisbane, Australia's central business district (CBD).
      Most of residents recognized the importance of environment protection and would
      like to lead a more environmentally friendly lifestyle. In addition, the majority
      were willing to pay higher prices for a living environment with sustainable
      features. The importance of positive social communications was emphasized with
      most residents having established good relationships with others in the village.
      The findings provide an important insight into consumer perspectives regarding
      the sustainable features that should and can be incorporated into the village
      planning and development. 

PMID- 25587451
TI  - Fatty Acid Composition of Egg Yolk from Chickens Fed a Diet including Marigold
      (Tagetes erecta L.).
AB  - The objective of this study was to determine the effects of diet supplemented
      with marigold on egg yolk fatty acid composition and egg quality parameters.
      Sixty hens were assigned into three groups and fed diets supplemented with 0
      (control), 10 g kg(-1), or 20 g kg(-1) marigold for 42 days. Eggs collected at
      the 6th week of the study were analyzed for fatty acid analysis. Laying
      performance, egg quality parameters, and feed intake were also evaluated. Yolk
      color scores in the group fed the 20 g kg(-1) marigold-supplemented diet were
      found greater than control (10.77 versus 9.77). Inclusion of 20 g kg(-1) marigold
      in diet influenced egg weights adversely compared to the control. Diet
      supplemented with 10 g kg(-1) or 20 g kg(-1) marigold increased the levels of
      C16:0 and C18:0 and decreased levels of C16:1 (n-7) and C18:1 (n-9) in the egg
      yolk. Also, diet including marigold increased total saturated fatty acids (SFA)
      and decreased monounsaturated fatty acids (MUFA) in the egg yolk. 

PMID- 25587449
TI  - A pilot study of an exercise-based patient education program in people with
      multiple sclerosis.
AB  - There is increasing evidence that physical exercise leads to numerous positive
      effects in PwMS. However, long-term effects of exercise may only be achievable if
      training is implemented in daily routine. Enabling patients to exercise
      regularly, we developed a patient education program focused on evidence-based
      information of training. PwMS were educated in neurophysiological effects of
      physical exercise, exercise-induced benefits for PwMS, and risk factors (e.g.,
      weather). Fifteen PwMS were analyzed before (T 0) and after (T 1) a 12-week
      patient education. Afterwards, participants performed their exercises
      autonomously for 32 weeks and were tested in sustainability tests (T 2). Guided
      interviews were carried out, additionally. Significant improvements from T 0 to T
      1 were found in 6MWT, gait velocity, TUG, fatigue, and quality of life.
      Significant results of TUG and gait velocity from T 1 to T 2 demonstrated that
      participants kept few effects after the 32-week training phase. Qualitative
      analyses showed improved self-confidence and identified training strategies and
      barriers. This pilot study provides evidence that PwMS are able to acquire good
      knowledge about physical exercise and apply this knowledge successfully in
      training management. One might conclude that this exercise-based patient
      education seems to be a feasible option to maintain or improve patients' integral
      constitution concerning physical and mental health. 

PMID- 25587450
TI  - Gastroschisis: antenatal sonographic predictors of adverse neonatal outcome.
AB  - OBJECTIVES: The aim of this review was to identify clinically significant
      ultrasound predictors of adverse neonatal outcome in fetal gastroschisis.
      METHODS: A quasi-systematic review was conducted in PubMed and Ovid using the key
      terms "gastroschisis," "predictors," "outcome," and "ultrasound." RESULTS: A
      total of 18 papers were included. The most common sonographic predictors were
      intra-abdominal bowel dilatation (IABD), intrauterine growth restriction (IUGR),
      and bowel dilatation not otherwise specified (NOS). Three ultrasound markers were
      consistently found to be statistically insignificant with respect to predicting
      adverse outcome including abdominal circumference, stomach herniation and
      dilatation, and extra-abdominal bowel dilatation (EABD). CONCLUSIONS:
      Gastroschisis is associated with several comorbidities, yet there is much
      discrepancy in the literature regarding which specific ultrasound markers best
      predict adverse neonatal outcomes. Future research should include prospective
      trials with larger sample sizes and use well-defined and consistent definitions
      of the adverse outcomes investigated with consideration given to IABD.

PMID- 25587452
TI  - Intraoperative full-dose of partial breast irradiation with electrons delivered
      by standard linear accelerators for early breast cancer.
AB  - Purpose. To assess feasibility, efficacy, toxicity, and cosmetic results of
      intraoperative radiotherapy (IORT) with electrons delivered by standard linear
      accelerators (Linacs) during breast conserving surgeries for early infiltrating
      breast cancer (BC) treatment. Materials and Methods. A total of 152 patients with
      invasive ductal carcinoma (T <= 3.0 cm) at low risk for local relapses were
      treated. All had unicentric lesions by imaging methods and negative sentinel
      node. After a wide local excision, 21 Gy were delivered on the parenchyma target
      volume with electron beams. Local recurrences (LR), survival, toxicity, and
      cosmetic outcomes were analyzed. Results. The median age was 58.3 years (range 40
      85); median follow-up was 50.7 months (range 12-101.5). There were 5 cases with
      LR, 2 cases with distant metastases, and 2 cases with deaths related to BC. The
      cumulative incidence rates of LR, distant metastases, and BC death were 3.2%,
      1.5%, and 1.5%, respectively. Complications were rare, and the cosmetic results
      were excellent or good in most of the patients. Conclusions. IORT with electrons
      delivered by standard Linacs is feasible, efficient, and well tolerated and seems
      to be beneficial for selected patients with early infiltrating BC. 

PMID- 25587453
TI  - Intraoperative Boost Radiotherapy during Targeted Oncoplastic Breast Surgery:
      Overview and Single Center Experiences.
AB  - Breast-conserving surgery followed by whole-breast irradiation is the standard
      local therapy for early breast cancer. The international discussion of reduced
      importance of wider tumor-free resection margins than "tumor not touching ink"
      leads to the development of five principles in targeted oncoplastic breast
      surgery. IORT improves local recurrence risk and diminishes toxicity since there
      is less irradiation of healthy tissue. Intraoperative radiotherapy (IORT) can be
      delivered in two settings: an IORT boost followed by a conventional regimen of
      external beam radiotherapy or a single IORT dose. The data from TARGIT-A and
      ELIOT reinforce the conviction that intraoperative radiotherapy during breast
      conserving surgery is a reliable alternative to conventional postoperative
      fractionated irradiation, but only in a carefully selected population at low risk
      of local recurrence. We describe our experiences with IORT boost (50 kV energy X
      rays; 20 Gy) in combination with targeted oncoplastic breast surgery in a routine
      clinical setting. Our experiences demonstrate the applicability and reliability
      of combining IORT boost with targeted oncoplastic breast surgery in breast
      conserving therapy of early breast cancer. 

PMID- 25587454
TI  - Differences in the malariometric indices of asymptomatic carriers in three
      communities in ibadan, Nigeria.
AB  - This study was conducted to determine the malariometric indices of children in
      three different settings in Ibadan, Nigeria. Children were recruited from an
      urban slum (Oloomi) and a periurban (Sasa) and a rural community (Igbanda) in
      Ibadan. Children aged between 2 and 10 years were randomly selected from primary
      schools in the urban and periurban areas. In the rural community, children were
      recruited from the centre of the village. A total of 670 (55.0%) out of 1218
      children recruited were positive for malaria parasitaemia. The urban population
      had the highest proportion of children with malaria parasitaemia. Splenomegaly
      was present in 31.5%, hepatomegaly in 41.5%, hepatosplenomegaly in 27.5%, and
      anaemia in 25.2% of the children. The parasite density was not significantly
      different among children in the three communities. Children in the rural
      community had the highest mean PCV of 34.2% and the lowest rates of splenomegaly
      (6.1%), hepatomegaly (7.6%), and hepatosplenomegaly (4.6%). The spleen rates,
      liver rates, and presence of hepatosplenomegaly and anaemia were similar in the
      urban and periurban communities. The malariometric indices among the asymptomatic
      carriers were high, especially in the urban slum. This stresses the need for
      intensified efforts at controlling the disease in the study area. 

PMID- 25587456
TI  - The drop that spilled the cup: acute myocardial infarction in a young woman with
      underlying thrombophilic polymorphisms and oral contraceptive use.
AB  - We present the case of a 28-year-old woman who was admitted to our cardiology
      unit for acute coronary syndrome. Her history was notable for cardiovascular
      disease familiarity, active smoking, and oral contraceptive use. On further
      analysis, she was noted to have thrombophilic polymorphisms involving the
      plasminogen activator inhibitor (PAI), angiotensin-converting enzyme (ACE), and
      methylenetetrahydrofolate reductase (MTHFR) genes. We discuss the implications
      that these cofactors may have had in the genesis of the disease. 

PMID- 25587457
TI  - Octreotide for the Management of Gastrointestinal Bleeding in a Patient with a
      HeartWare Left Ventricular Assist Device.
AB  - HeartWare is a third generation left ventricular assist device (LVAD), widely
      used for the management of advanced heart failure patients. These devices are
      frequently associated with a significant risk of gastrointestinal (GI) bleeding.
      The data for the management of patients with LVAD presenting with GI bleeding is
      limited. We describe a 56-year-old lady, recipient of a HeartWare device, who
      experienced recurrent GI bleeding and was successfully managed with subcutaneous
      (SC) formulations of octreotide. 

PMID- 25587455
TI  - Auditory cortex tACS and tRNS for tinnitus: single versus multiple sessions.
AB  - Tinnitus is the perception of a sound in the absence of an external acoustic
      source, which often exerts a significant impact on the quality of life. Currently
      there is evidence that neuroplastic changes in both neural pathways are involved
      in the generation and maintaining of tinnitus. Neuromodulation has been suggested
      to interfere with these neuroplastic alterations. In this study we aimed to
      compare the effect of two upcoming forms of transcranial electrical
      neuromodulation: alternating current stimulation (tACS) and random noise
      stimulation (tRNS), both applied on the auditory cortex. A database with 228
      patients with chronic tinnitus who underwent noninvasive neuromodulation was
      retrospectively analyzed. The results of this study show that a single session of
      tRNS induces a significant suppressive effect on tinnitus loudness and distress,
      in contrast to tACS. Multiple sessions of tRNS augment the suppressive effect on
      tinnitus loudness but have no effect on tinnitus distress. In conclusion this
      preliminary study shows a possibly beneficial effect of tRNS on tinnitus and can
      be a motivation for future randomized placebo-controlled clinical studies with
      auditory tRNS for tinnitus. Auditory alpha-modulated tACS does not seem to be
      contributing to the treatment of tinnitus. 

PMID- 25587458
TI  - Compound composite odontoma and its management.
AB  - Odontomas are odontogenic benign tumors composed of dental tissue. Majority of
      these lesions are asymptomatic and are often detected on routine radiographs.
      They can be thought of as "tooth hamartomas" with the lesion consisting of
      various tooth components. They are divided histologically into complex odontomas
      and compound odontomas. This paper describes the case of a compound odontoma in a
      13-year-old girl diagnosed due to the retention of the primary right mandibular
      second molar. A surgical excision was performed without disturbing the unerupted
      premolar. The results achieved indicate that early diagnosis of odontomas enables
      adoption of less complex treatment, a better prognosis, and displacement or
      devitalisation of adjacent tooth. 

PMID- 25587459
TI  - Cartilaginous choristoma of the gingiva: a rare clinical entity.
AB  - Choristomas are rare entities which are aggregates of microscopically normal
      cells or tissues in aberrant locations. They are a "heterotopic" rest of cells,
      as they appear as a tumor-like mass. Herein we report a case of cartilaginous
      choristoma in a 54-year-old male who presented with a swelling on right lower
      gingiva. The histopathological examination revealed features of a well
      circumscribed mass of mature cartilage in a dense fibrous connective tissue
      stroma. 

PMID- 25587460
TI  - Fraser syndrome-oral manifestations and a dental care protocol.
AB  - Fraser syndrome is a rare genetic malformation with an autosomal recessive
      pattern of inheritance and an incidence of consanguinity ranging from 15% to 25%.
      A 5-year-old male patient who is a carrier of Fraser syndrome initiated treatment
      in the pediatric dentistry sector. The patient was fed parenterally since birth,
      experienced recurring bouts of chronic lung disease, and was referred to the
      pediatric dentistry sector by the medical team. Radiographic examination revealed
      the presence of all permanent teeth. Supragingival dental calculus, halitosis,
      and gingival inflammation were also observed. Dental calculus was removed by
      manual scraping, and chemotherapeutic agents were used, chlorhexidine 0,12%,
      chlorhexidine gel 2%, and PVP-I, to control the bacterial flora. The patient is
      still being monitored after an 8-year follow-up period, the complications
      associated with periodontal disease decreased, and since the initiation of
      treatment, the patient has not needed to be hospitalized because of chronic lung
      disease. This study reports the case of a patient diagnosed with Fraser syndrome
      and describes the clinical manifestations (general and oral). 

PMID- 25587461
TI  - Craniodentofacial Manifestations in a Rare Syndrome: Orofaciodigital Type IV
      (Mohr-Majewski Syndrome).
AB  - Background. The orofaciodigital syndromes (OFDS) are a heterogeneous group of
      syndromes that affect the face, oral cavity, and the digits. OFDS type IV (OMIM
      %258860) is rare and characterized by broad nasal root and tip, orbital
      hypertelorism or telecanthus, micrognathia, hypoplastic mandible, and low-set
      ears. Oral symptoms may include cleft lip, cleft or highly arched palate, bifid
      uvula, cleft or hypoplastic maxillary and mandibular alveolar ridge, oral
      frenula, lingual hamartoma, and absent or hypoplastic epiglottis. Dental
      anomalies are common and generally include disturbances in the number of teeth.
      Case Report. This report presents a six-year-old girl, referred with the chief
      complaint of missing teeth. She was diagnosed as having OFDS type IV based on
      clinical findings. Her parents reported three deceased children and two fetuses
      that had the same phenotype. She was the seventh child of consanguineous parents
      who were first cousins. Conclusion. This is a very rare syndrome. Many reported
      OFDS type IV cases have consanguineous parents, consistent with an autosomal
      recessive trait. Manifestation of cleft palate in the healthy sibling may be mild
      expression of the disorder or an unrelated isolated cleft. 

PMID- 25587462
TI  - Rare periodontal ligament drainage for periapical inflammation of an adjacent
      tooth: a case report and review of the literature.
AB  - Aim. To report a case with an unusual drainage route of periapical inflammation
      exiting through the gingival sulcus of an adjacent vital tooth and review
      probable factors determining the diversity of the discharge routes of periapical
      inflammation. Summary. An 18-year-old male patient presented with periodontal
      abscess of tooth 46, which was found to be caused by a periapical cyst with an
      acute abscess of tooth 45. During endodontic surgery, a rarely reported drainage
      route for periapical inflammation via the gingival sulcus of an adjacent vital
      tooth was observed for the first time. Complete periodontal healing of the deep
      pocket of tooth 46 and hiding of the periapical cyst of tooth 45 followed after
      root canal treatment and periapical surgery with Bio-Oss Collagen implantation on
      tooth 45. The drainage routes of periapical inflammation are multivariate and the
      diversity of drainage pathways of periapical inflammation is mainly related to
      factors such as gravity, barriers against inflammation, and the causative tooth
      itself. 

PMID- 25587463
TI  - Unilateral fusion of maxillary lateral incisor: diagnosis using cone beam
      computed tomography.
AB  - Objective. The objective of this paper is to report a dental fusion case focusing
      on clinical and radiographic features for the diagnosis. Method. To report a case
      of right maxillary lateral incisor fusion and a supernumerary tooth, the anatomy
      of the root canal and dental united portion were assessed by cone beam computed
      tomography (CBCT). Results. The clinical examination showed dental juxtaposition
      with the absence of interdental papilla and esthetic impairment in the right
      maxillary lateral incisor region. The periapical radiography did not provide
      enough information for the differential diagnosis due to the inherent limitations
      of this technique. CBCT confirmed the presence of tooth fusion. Conclusion. CBCT
      examination supports the diagnosis and provides both the identification of
      changes in tooth development and the visualization of their extent and limits. 

PMID- 25587464
TI  - Angioedema due to Systemic Isotretinoin Therapy.
AB  - Angioedema is the swelling of the mucosal membranes as a variant of urticaria
      induced by hereditary C1 esterase inhibitor enzyme deficiency, certain foods, or
      drugs. Herein, we report the case of a 23-year-old woman, with mild-moderate acne
      presenting with widespread facial angioedema on the 2nd day of systemic
      isotretinoin treatment. The patient had taken no drugs other than isotretinoin in
      the preceding days and had no known food allergy. Her angioedema was resolved
      after the isotretinoin was discontinued. We want to draw the attention of
      dermatologists to this rare adverse allergic effect of isotretinoin which is
      frequently used in the treatment of acne vulgaris. 

PMID- 25587465
TI  - Paraneoplastic dermatomyositis with carcinoma cervix: a rare clinical
      association.
AB  - Dermatomyositis is an uncommon inflammatory myopathy associated with cutaneous
      manifestations. It may also occur as paraneoplastic syndrome associated with
      various malignancies, most common of which being lung, breast, stomach, rectum,
      kidney, or testicular cancer. A postmenopausal woman presented to us with
      generalized itching along with skin rash and proximal muscle weakness of 2 years'
      duration. Examination revealed heliotrope rash and mechanic hands and muscle
      power 2/5 in proximal muscle groups of both upper and lower limbs. A clinical
      diagnosis of dermatomyositis was made which was supported by raised lactate
      dehydrogenase levels and skin biopsy findings. Past history was significant for
      vaginal discharge and bleeding per vagina. Further work-up revealed carcinoma
      cervix and she was referred to oncology department for further management.
      Temporal relationship and improvement of muscle weakness with treatment of
      underlying neoplasm supported its paraneoplastic nature. So, final diagnosis of
      keratinizing squamous cell carcinoma of cervix with paraneoplastic
      dermatomyositis was made. A nationwide cohort study of 1,012 patients with
      dermatomyositis in Taiwan revealed only 3 patients with cervical cancer. So this
      case is being reported for its rare association with carcinoma cervix and to
      highlight the need of detailed evaluation for underlying malignancies in patients
      with dermatomyositis. 

PMID- 25587466
TI  - A vertebral artery dissection with basilar artery occlusion in a child.
AB  - This paper presents the case report of an 11-year-old boy with an acute
      dissection with thrombosis of the left vertebral artery and thrombosis of the
      basilar artery. The patient was treated with acute systemic thrombolysis,
      followed by intra-arterial thrombolysis, without any clinical improvement,
      showing left hemiplegia, bilateral clonus, hyperreflexia, and impaired
      consciousness. MRI indicated persistent thrombosis of the arteria basilaris with
      edema and ischemia of the right brainstem. Heparinization for 72 hours, followed
      by a two-week LMWH treatment and subsequent oral warfarin therapy, resulted in a
      lasting improvement of the symptoms. Vertebral artery dissection after minor
      trauma is rare in children. While acute basilar artery occlusion as a
      complication is even more infrequent, it is potentially fatal, which means that
      prompt diagnosis and treatment are imperative. The lack of class I recommendation
      guidelines for children regarding treatment of vertebral artery dissection and
      basilar artery occlusion means that initial and follow-up management both require
      a multidisciplinary approach to coordinate emergency, critical care,
      interventional radiology, and child neurology services. 

PMID- 25587467
TI  - Pediatric stroke presenting as a seizure.
AB  - Background. Childhood arterial ischemic stroke (AIS) is rare and may be difficult
      to diagnose. Management of acute stroke in any age group is time sensitive, so
      awareness of the manifestations and appropriate diagnostic procedures for
      pediatric AIS is vital to establishing care. We present a pediatric case of
      arterial ischemic stroke that presented to the emergency department (ED) after
      two seizures. Case Report. A five-year-old female with an existing seizure
      disorder presented to a pediatric ED after having two seizures. Postictal upon
      arrival, she underwent a computed tomography (CT) scan of her head. Family
      reported that she had complained of a severe headache and vomited; her seizures
      were described as different from those she had experienced in the past. Loss of
      grey white matter differentiation on the CT warranted magnetic resonance imaging
      (MRI), which demonstrated a right-sided stroke. After a complicated course in the
      hospital, the patient was discharged to a rehabilitation hospital. Why Should an
      Emergency Physician Be Aware of This? It is important that emergency physicians
      recognize that a seizure may be the initial symptom of a pediatric stroke
      regardless of an established seizure history. Pediatric seizures are relatively
      common; however consideration of the diagnosis of pediatric stroke may prevent
      unnecessary delays in treatment. 

PMID- 25587468
TI  - Spontaneous Regression of a Carcinoid Tumor following Pregnancy.
AB  - We present a case of spontaneous regression of a neuroendocrine tumor following
      pregnancy in the absence of chemotherapy, radiotherapy, or alternative medicine
      (including herbal medicine). The diagnosis of a nonsecretory carcinoid tumor was
      confirmed using CT imaging, octreotide scan, and histology. Furthermore, serial
      imaging has demonstrated spontaneous regression of the carcinoid suggesting that
      pregnancy did not worsen the course of the disease but instead may have
      contributed to tumour regression. We discuss mechanisms underlying tumour
      regression and the possible effect of pregnancy on these processes. 

PMID- 25587469
TI  - Metastatic hepatocellular carcinoma in a patient with Crohn's disease treated
      with azathioprine and infliximab: a case report and literature review.
AB  - Hepatocellular carcinoma most commonly occurs in patients with underlying liver
      disease or cirrhosis. We describe a case of hepatocellular carcinoma in a 34-year
      old man with Crohn's disease treated with azathioprine and infliximab. The
      patient had no history of liver disease and a complete autoimmune and viral
      workup was unremarkable. Unfortunately, the patient developed widespread
      metastatic disease and passed away 5 months after his initial diagnosis. The
      mechanism of hepatocellular carcinoma in patients' with Crohn's disease is poorly
      understood and may include both autoimmunity and treatment-related complications.
      Previous case reports suggest the possibility of a concerning association between
      azathioprine therapy and the development of hepatocellular carcinoma in patients
      with Crohn's disease. Clinicians may consider early imaging in patients with
      Crohn's disease presenting with concerning symptomatology or abnormal liver
      enzymes, especially in those being treated with azathioprine alone or in
      combination with infliximab. Future research may help to uncover additional risk
      factors for this exceedingly rare diagnosis in this patient population. 

PMID- 25587470
TI  - Adult T-cell lymphoma/leukemia presenting as isolated central nervous system T
      cell lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with
      infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central
      nervous system (CNS) involved by ATLL is often occurred in advanced disease, such
      as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is
      rare. We repot a 50-year-old woman who presented with multiple infiltrative brain
      lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of
      brain tumor indicated CNS vasculitis. The patient received one course of high
      dose methotrexate and MR imaging of brain revealed remission of infiltrative
      lesions. Two years later, new brain lesions were detected. Histopathologic
      examination of specimens via craniotomy revealed T-cell lymphoma. The patient
      responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation
      was performed. Six months later, the patient had hepatosplenomegaly,
      hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in
      circulation. Results of flow cytometry analysis of peripheral blood indicated
      ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected.
      Clinicians should screen HTLV-1 infection when patients are diagnosed with
      peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy
      may improve the outcomes of ATLL. 

PMID- 25587471
TI  - Severe Aplastic Anemia following Acute Hepatitis from Toxic Liver Injury:
      Literature Review and Case Report of a Successful Outcome.
AB  - Hepatitis associated aplastic anemia (HAAA) is a rare syndrome in which severe
      aplastic anemia (SAA) complicates the recovery of acute hepatitis (AH). HAAA is
      described to occur with AH caused by viral infections and also with idiopathic
      cases of AH and no clear etiology of liver injury. Clinically, AH can be mild to
      fulminant and transient to persistent and precedes the onset SAA. It is assumed
      that immunologic dysregulation following AH leads to the development of SAA.
      Several observations have been made to elucidate the immune mediated injury
      mechanisms, ensuing from liver injury and progressing to trigger bone marrow
      failure with the involvement of activated lymphocytes and severe T-cell
      imbalance. HAAA has a very poor outcome and often requires bone marrow transplant
      (BMT). The findings of immune related myeloid injury implied the use of
      immunosuppressive therapy (IST) and led to improved survival from HAAA. We report
      a case of young male who presented with AH resulting from the intake of muscle
      building protein supplements and anabolic steroids. The liver injury slowly
      resolved with supportive care and after 4 months of attack of AH, he developed
      SAA. He was treated with IST with successful outcome without the need for a BMT. 

PMID- 25587472
TI  - Sudden Death by Pulmonary Thromboembolism due to a Large Uterine Leiomyoma with a
      Parasitic Vein to the Mesentery.
AB  - The pathophysiology of venous thrombosis is classically attributed to alterations
      in one or more components of Virchow's triad: hypercoagulability, stasis, and
      damage to the vascular endothelium. Deep vein thrombosis (DVT) may lead to
      pulmonary thromboembolism (PE), and the latter is culpable for many deaths
      annually in the United States; however, DVT as a complication of uterine
      leiomyoma has rarely been reported. We report a case of a 57-year-old woman whose
      death was due to a large pedunculated subserosal leiomyoma externally compressing
      the pelvic veins resulting in stasis and venous thrombosis leading to fatal PE.
      The association of large pelvic masses with venous thrombosis has clinical
      implications, since prophylactic surgery could be life-saving. 

PMID- 25587473
TI  - Genital Schistosomiasis: A Report on Two Cases of Ovarian Carcinomas Containing
      Viable Eggs of Schistosoma mansoni.
AB  - Schistosomiasis is a parasitic infection that is highly prevalent worldwide, with
      a variety of species being responsible for causing the disease. In Brazil,
      however, the only identified species is Schistosoma mansoni. The adult parasites
      inhabit the blood vessels of the hepatic portal system of the main host. The
      disease may range from being asymptomatic to provoking liver damage or portal
      hypertension. Furthermore, ectopic schistosomiasis may develop, and several
      hypotheses have been raised to explain the occurrence of the disease. This paper
      describes two cases, one in a 39-year-old woman and the other in a 47-year-old
      woman. Both had similar symptoms of pain and abdominal distension caused by a
      large abdominal/pelvic mass. Histopathology of the ovary showed a mucinous
      cystadenocarcinoma of the intestinal type in the first patient and a papillary
      serous carcinoma in the second, with both tumors containing viable eggs of
      Schistosoma mansoni. The neoplasms probably serve as a migratory route for the
      adult parasites and the embolization of eggs. Nevertheless, there is insufficient
      evidence to confirm the malignization of a benign lesion due to the presence of
      Schistosoma mansoni. Few cases have been reported in the international literature
      on the association between ovarian schistosomiasis and neoplasms. 

PMID- 25587474
TI  - Unusual presentation of a rectovestibular fistula as gastrointestinal hemorrhage
      in a postmenopausal woman.
AB  - Background. Anorectal malformations (ARMs) are extremely rare and are usually
      identified neonatally. It is unusual for these cases to present in the
      postmenopausal period. This case report describes a postmenopausal patient with
      ARM and rectovaginal hemorrhage. Case. An 86-year-old, gravida 11, para 9,
      presented to the emergency department complaining of profuse postmenopausal
      vaginal bleeding. Her gynecologic history was significant only for an unclear
      history of an anal abnormality that was noted at birth. Speculum examination
      revealed profuse rectal bleeding from a rectovestibular fistula exterior to her
      hymenal ring. Colonoscopic examination revealed severe diverticular disease.
      Conclusion. This patient was born with an imperforate anus which resolved as
      rectovestibular fistula and ectopic anus. This case presents a rare clinical
      circumstance which integrates the fields of obstetrics, gynecology,
      gastroenterology, and embryology alike. 

PMID- 25587475
TI  - Adult alveolar soft part sarcoma of the head and neck: a report of two cases and
      literature review.
AB  - Background. Alveolar soft part sarcomas (ASPS) of the head and neck are rare,
      aggressive soft-tissue malignancies. This study describes the clinical course and
      management of two patients presenting with ASPS in very rare head and neck
      locations, the larynx and parotid gland. Methods. We identified two patients
      presenting with ASPS of the head and neck and treated at the University of North
      Carolina. We compared our results to the literature from 1987 to 2013. Results.
      Patient ages at diagnosis were 27 and 39 with presenting symptoms of hoarseness
      and parotid swelling, respectively. Mean follow-up was 87 months. All patients
      received surgical resection and adjuvant radiotherapy. There were no recurrences
      or evidence of distant metastatic spread during the series. Disease-free survival
      time for the patients was 4 months and 168 months, respectively. Conclusions. Our
      study suggests that a combined-modality approach is important in the treatment of
      ASPS of the head and neck even in these rare locations. Continued research into
      new therapies is necessary to improve historically poor outcomes. 

PMID- 25587476
TI  - Compartment Syndrome following Open Femoral Fracture with an Isolated Femoral
      Vein Injury Treated with Acute Repair.
AB  - Acute compartment syndrome is a surgical emergency and its diagnosis is more
      difficult in obtunded or insensate patients. We present the case of a 34-year-old
      woman who sustained a Gustilo-Anderson grade III open midshaft femur fracture
      with an isolated femoral vein injury treated with direct repair. She developed
      lower leg compartment syndrome at 48 hours postoperatively, necessitating
      fasciotomies. She was subsequently found to have a DVT in her femoral vein at the
      level of the repair and was started on therapeutic anticoagulation. This case
      highlights the importance of recognition of isolated venous injuries in a trauma
      setting as a risk factor for developing compartment syndrome. 

PMID- 25587478
TI  - Osteoclastic giant cell rich squamous cell carcinoma of the uterine cervix: a
      case report and review of the literature.
AB  - Cervical carcinoma is the most common malignancy of the female genital tract and
      represents the second most common malignancy in women worldwide. Histologically
      85 to 90% of cervical cancers are squamous cell carcinoma. Osteoclastic giant
      cell rich squamous cell carcinoma is an unusual histological variant of which
      only 4 cases have been reported. We present the case of a 49-year-old woman with
      a 6-month history of irregular vaginal bleeding. Examination revealed a 2.7 cm
      polypoid mass in the anterior lip of the uterine cervix. The patient underwent
      hysterectomy with bilateral salpingo-oophorectomy. Microscopically the tumor was
      composed of infiltrative nests of poorly differentiated nonkeratinizing squamous
      cell carcinoma. Interspersed in between these tumor cells were numerous
      osteoclastic giant cells with abundant eosinophilic cytoplasm devoid of nuclear
      atypia, hyperchromatism, or mitotic activity. Immunohistochemistry was performed;
      CK and P63 were strongly positive in the squamous component and negative in the
      osteoclastic giant cells, while CD68 and Vimentin were strongly positive in the
      giant cell population and negative in the squamous component. The patient
      received chemo- and radiotherapy for recurrent disease identified 3 months later
      on a follow-up CT scan; 7 months after the surgical procedure the patient is
      clinically and radiologically disease-free. 

PMID- 25587477
TI  - Carcinosarcoma of the ureter with a small cell component: report of a rare
      pathologic entity and potential for diagnostic error on biopsy.
AB  - Carcinosarcomas of the ureter are rare biphasic neoplasms, composed of both
      malignant epithelial (carcinomatous) and malignant mesenchymal (sarcomatous)
      components. Carcinosarcomas of the urinary tract are exceedingly rare. We report
      a unique case of a carcinosarcoma of the ureter with a chondrosarcoma and small
      cell tumor component arising in a 68-year-old male who presented with microscopic
      hematuria. CT intravenous pyelogram revealed right-sided hydroureter and
      hydronephrosis with thickening and narrowing of the right ureter. The patient
      underwent robot-assisted ureterectomy with bladder cuff excision and subsequent
      adjuvant chemotherapy. The patient is disease-free at 32 months after treatment.
      We provide a brief synoptic review of carcinosarcoma of the ureter and bladder
      with utilization of immunohistochemical (IHC) stains and potential diagnostic
      pitfalls. 

PMID- 25587479
TI  - Unilateral heliotrope rash in juvenile dermatomyositis: an unusual presentation
      of an underlying serious disease.
AB  - Background. Heliotrope rash is one of the characteristic skin manifestations of
      juvenile dermatomyositis. It is a reddish-purple rash on the upper eyelids that
      is usually bilateral. Case Presentation. We report a boy who presented with
      unilateral heliotrope rash, Gottron's papules, and muscle weakness. Muscle biopsy
      was consistent with inflammatory myositis. Patient was started on prednisolone
      and methotrexate with an excellent response in both the skin and muscles.
      Conclusion. Unilateral heliotrope rash can occur in patients with juvenile
      dermatomyositis. Being a paraneoplastic condition caution should be taken not to
      miss any underlying malignancy. 

PMID- 25587480
TI  - Radical resection of a late-relapsed testicular germ cell tumour: hepatectomy,
      cavotomy, and thrombectomy.
AB  - Up to 3.2% of patients with testicular germ cell tumours represent with late
      relapsing disease. Aggressive surgical resection confers the greatest chance of
      cure in this patient group. We present the case of a late and extensively
      relapsed nonseminomatous germ cell tumour with thrombus present along the entire
      length of the inferior vena cava, as well as in the right hepatic vein.
      Techniques practised in liver transplantation were used to achieve complete
      resection of the tumour thrombus. This case illustrates the enhanced potential
      for tumour resection through a fusion of principles derived from surgical
      oncology and liver transplantation. 

PMID- 25587482
TI  - Isolated bilateral renal mucormycosis masquerading as renal abscess in an
      immunocompetent individual: a lesson learnt.
AB  - Isolated renal mucormycosis is a rare entity in immunocompetent subjects. It is
      usually a rapidly progressive disease with poor prognosis but it can mimic renal
      abscess with a protracted course. 

PMID- 25587481
TI  - Bladder perforation secondary to primary systemic amyloidosis.
AB  - Amyloidosis is a disorder of protein folding characterized by extracellular
      aggregation and deposition of amyloid protein fibrils. Light-chain amyloidosis,
      also known as primary systemic amyloidosis, is the most common form of the
      disease. We present a case of an 84-year-old male with a history of systemic
      primary amyloidosis causing genitourinary, cardiac, and autonomic dysfunction who
      presented with hematuria and hypotension secondary to bladder perforation. He
      underwent open repair of a large extraperitoneal bladder defect. He ultimately
      died as a result of medical complications from his disease. 

PMID- 25587483
TI  - Bilateral double ureters with bladder neck diverticulum in a nigerian woman
      masquerading as an obstetric fistula.
AB  - A 43-year-old woman presented with 20-year history of leakage of urine per
      vaginam. She had one failed repair attempt. Pelvic examination with dye test
      showed leakage of clear urine suggestive of ureterovaginal fistula. The
      preoperative intravenous urogram revealed duplex ureter and cystoscopy showed
      normally cited ureteric orifices with two other ectopic ureteric openings and
      bladder diverticula. The definitive surgery performed was ureteric reimplantation
      (ureteroneocystostomy) of the two distal ureteric to 2 cm superiolateral to the
      two normal orifices and diverticuloplasty. There was resolution of urinary
      incontinence after surgery. Three months after surgery, she had urodynamic
      testing done (cystometry), which showed 220 mLs with no signs of instability or
      leakage during filling phase but leaked on coughing at maximal bladder capacity.
      This is to showcase some diagnostic dilemma that could arise with obstetric
      fistula, which is generally diagnosed by clinical assessment. 

PMID- 25587484
TI  - Distinct lysosome phenotypes influence inflammatory function in peritoneal and
      bone marrow-derived macrophages.
AB  - Lysosomes play a critical role in the degradation of both extracellular and
      intracellular material. These dynamic organelles also contribute to nutrient
      sensing and cell signaling pathways. Macrophages represent a heterogeneous group
      of phagocytic cells that contribute to tissue homeostasis and inflammation.
      Recently, there has been a renewed interest in understanding the role of
      macrophage autophagy and lysosome function in health and disease. Thioglycollate
      elicited peritoneal and bone marrow-derived macrophages are commonly used ex vivo
      systems to study primary macrophage function. In this study, we reveal dramatic
      baseline differences in the lysosome morphology and function between these
      macrophage populations and provide evidence that these differences can be
      functionally relevant. Our results provide important insights into the diversity
      of lysosomes in primary macrophages and illustrate the importance of accounting
      for this in data interpretation. 

PMID- 25587485
TI  - Treatment for Osteoporosis among Women in Japan: Associations with Patient
      Characteristics and Patient-Reported Outcomes in the 2008-2011 Japan National
      Health and Wellness Surveys.
AB  - This study was conducted to identify characteristics associated with treatment
      for osteoporosis among women aged 50 years and older in Japan and to explore
      differences among patients according to treatment regimen. Data were provided by
      a large annual survey representative of Japanese aged 18 and older; all measures
      were by self-report. Women aged 50 and older who reported diagnosed osteoporosis
      (N = 900) were compared based on current treatment status using bivariate
      statistics and logistic regression. Approximately 1 in 3 women in this study
      reporting diagnosed osteoporosis were currently untreated. Factors associated
      with current treatment for osteoporosis included having >=1 physician visit in
      the prior 6 months (OR = 5.4, P < 0.001), self-rated moderate or severe
      osteoporosis (OR = 2.8, P < 0.001), completion of menopause (OR = 1.6, P < 0.05),
      and family history of osteoporosis (OR = 1.5, P < 0.05), while longer duration of
      osteoporosis diagnosis (OR = 0.9, P < 0.05) and arthritis (OR = 0.7, P < 0.05)
      were associated with lower odds of treatment. These findings suggest that
      diagnosed patients are not being actively managed in the longer term, and efforts
      need to be made to ensure that patients stay engaged with their healthcare
      providers. 

PMID- 25587488
TI  - Determination of beta -Cyano-L-alanine, gamma -Glutamyl- beta -cyano-L-alanine,
      and Common Free Amino Acids in Vicia sativa (Fabaceae) Seeds by Reversed-Phase
      High-Performance Liquid Chromatography.
AB  - A method for determination of beta-cyano-L-alanine, gamma-glutamyl-beta-cyano-L
      alanine and other free amino acids in Vicia sativa is presented. Seed extracts
      were derivatized by reaction with diethyl ethoxymethylenemalonate and analyzed by
      reverse-phase high-performance liquid chromatography. Calibration curves showed
      very good linearity of the response. The limit of detection and quantification
      was 0.15 and 0.50 MUM, respectively. The method has high intra- (RSD = 0.28
      0.31%) and interrepeatability (RSD = 2.76-3.08%) and remarkable accuracy with a
      99% recovery in spiked samples. The method is very easy to carry out and allows
      for ready analysis of large number of samples using very basic HPLC equipment
      because the derivatized samples are very stable and have very good
      chromatographic properties. The method has been applied to the determination of
      gamma-glutamyl-beta-cyano-L-alanine, beta-cyano-L-alanine, and common free amino
      acids in eight wild populations of V. sativa from southwestern Spain. 

PMID- 25587487
TI  - Measuring hemoglobin levels in the optic disc of Parkinson's disease patients
      using new colorimetric analysis software.
AB  - Objective. To evaluate a new method of measuring hemoglobin (Hb) levels and
      quantifying the color changes in the optic nerve head of Parkinson's disease (PD)
      patients. We also compared differences in retinal nerve fiber layer (RNFL)
      thicknesses obtained using spectral domain optical coherence tomography (OCT)
      device between PD group and healthy group. Methods. One hundred and fifty-five PD
      patients and 91 sex- and age-matched healthy subjects were included in this cross
      sectional study. OCT examinations and one photograph of the optic disc were
      performed. The Laguna ONhE ("optic nerve hemoglobin"; Insoft SL, Tenerife, Spain)
      software was used to analyze the Hb level on the acquired optic disc photographs.
      Results. PD patients exhibited significantly reduced mean optic disc Hb
      percentages (57.56% in PD, 67.63% in healthy subjects; P = 0.001) as well as
      reduced Hb in almost all analyzed sectors, with the largest differences detected
      in the inferior and nasal sectors. RNFL parameters were significantly reduced in
      PD patients compared with healthy subjects, especially in the inferior quadrant.
      Conclusions. Measurements of optic disc Hb levels obtained with the Laguna ONhE
      software had good ability to detect optic nerve color changes (more papillary
      paleness and consequently this could suggest optic atrophy and axonal loss) in PD
      patients. 

PMID- 25587486
TI  - Evidence of insulin resistance in adult uncomplicated malaria: result of a two
      year prospective study.
AB  - The study aimed at investigating the effects of adult uncomplicated malaria on
      insulin resistance. Fasting levels of blood glucose (FBG), glycosylated
      hemoglobin (HbA1c), and serum insulin were measured in 100 diabetics and 100 age
      matched controls before and during Plasmodium falciparum malaria. Insulin
      resistance and beta cell function were computed by homeostatic models assessment
      of insulin resistance (HOMAIR) and beta cell function (HOMAB) formulae,
      respectively. Body mass index (BMI) was computed. At baseline, diabetics had
      significantly (P < 0.05) higher levels of BMI, FBG, HbA1c, and HOMAIR but lower
      level of HOMAB than controls. Baseline insulin levels were comparable (P > 0.05)
      between the two study groups. During malaria, diabetics maintained significantly
      (P < 0.05) higher levels of BMI, FBG, and HbA1c but lower levels of insulin and
      HOMAB than controls. Malaria-induced HOMAIR levels were comparable (P > 0.05)
      between the two study groups but higher than baseline levels. Apart from BMI and
      HOMAB, mean levels of all the remaining parameters increased in malaria-infected
      controls. In malaria-infected diabetics, significant (P < 0.05) increase was only
      observed for insulin and HOMAIR but not the other measured parameters.
      Uncomplicated malaria increased insulin resistance in diabetics and controls
      independent of BMI. This finding may have implications for the evolution of T2DM
      in malaria-endemic regions. 

PMID- 25587489
TI  - Quantification of Caffeoylquinic Acids in Coffee Brews by HPLC-DAD.
AB  - The influence of different brewing conditions on the concentration of the main
      caffeoylquinic acids (3-caffeoylquinic acid (3-CQA), 4-caffeoylquinic acid (4
      CQA), and 5-caffeoylquinic acid (5-CQA)) was investigated. For this purpose,
      twenty-four coffee brews were extracted and analyzed using HPLC-DAD at 325 nm.
      Our findings demonstrate the great impact of brewing techniques on the
      caffeoylquinic acids (CQAs) content. The major isomer was 3-CQA, accounting for
      about 50% of the total CQAs, followed by 5-CQA and 4-CQA, accounting for about 24
      36% for each one. The total content of CQAs was in the range of 45.79 to 1662.01
      mg/L, found in iced cappuccino and pod espresso, respectively. In conclusion,
      this study demonstrates that coffee brews, in particular those prepared using
      pressurized methods, can be considered as the potential sources of antioxidants
      such as CQAs. 

PMID- 25587490
TI  - Primary injuries and secondary organ failures in trauma patients with acute
      kidney injury treated with continuous renal replacement therapy.
AB  - Background. Acute kidney injury (AKI) treated with continuous renal replacement
      therapy (CRRT) is a severe complication in trauma patients. The aim of the study
      was to assess primary traumatic injuries and secondary organ failures in severe
      posttraumatic AKI. Methods. Retrospective review of adult trauma patients
      admitted to the trauma centre at Oslo University Hospital Ulleval. Injury
      severity score (ISS) was used to assess the severity of primary injuries, and
      sequential organ failure assessment (SOFA) score was utilized to measure
      secondary organ failures. Results. Forty-two (8%) of 506 trauma patients admitted
      to intensive care unit developed AKI treated with CRRT, whereof 40 (95%) suffered
      blunt trauma mechanisms. Patients had extensive primary organ injuries with
      median (interquartile range) ISS 36 (27-49). The majority of the patients had
      respiratory (93% intubated) and cardiovascular (67% with inotropic and/or
      vasoactive medication) failure within 24 hours after admission. AKI was often
      part of multiple organ failure, most frequently respiratory and cardiovascular
      failure, affecting 33 (75%) and 30 (71%) of the patients, respectively.
      Conclusion. Trauma patients with AKI undergoing CRRT often had severe primary
      injuries due to blunt trauma. Most of them suffered from secondary multiple organ
      failure concomitant to AKI. 

PMID- 25587492
TI  - Biodefense Oriented Genomic-Based Pathogen Classification Systems: Challenges and
      Opportunities.
AB  - Countermeasures that will effectively prevent or diminish the impact of a
      biological attack will depend on the rapid and accurate generation and analysis
      of genomic information. Because of their increasing level of sensitivity, rapidly
      decreasing cost, and their ability to effectively interrogate the genomes of
      previously unknown organisms, Next Generation Sequencing (NGS) technologies are
      revolutionizing the biological sciences. However, the exponential accumulation
      microbial data is equally outpacing the computational performance of existing
      analytical tools in their ability to translate DNA information into reliable
      detection, prophylactic and therapeutic countermeasures. It is now evident that
      the bottleneck for next-generation sequence data analysis will not be solved
      simply by scaling up our computational resources, but rather accomplished by
      implementing novel biodefense-oriented algorithms that overcome exiting
      vulnerabilities of speed, sensitivity and accuracy. Considering these
      circumstances, this document highlights the challenges and opportunities that
      biodefense stakeholders must consider in order to exploit more efficiently
      genomic information and translate this data into integrated countermeasures. The
      document overviews different genome analysis methods and explains concepts of DNA
      fingerprints, motif fingerprints, genomic barcodes and genomic signatures. A
      series of recommendations to promote genomics and bioinformatics as an effective
      form of deterrence and a valuable scientific platform for rapid technological
      insertion of detection, prophylactic, therapeutic countermeasures are discussed.

PMID- 25587493
TI  - Use of non-benzodiazepine sedative hypnotics and risk of falls in older men.
AB  - BACKGROUND: To ascertain whether use of non-benzodiazepine sedative-hypnotics is
      associated with risk of falls and compare this to risk of falls associated with
      use of benzodiazepines. METHODS: Among 4450 community-dwelling men, aged 71 years
      and older, enrolled in the population-based prospective cohort study,
      Osteoporotic Fractures in Men (MrOS), use of nonbenzodiazepine sedative-hypnotics
      and benzodiazepines was assessed by interview and verified from medication
      containers at the third annual visit of the MrOS study. Falls in the subsequent
      one-year period were ascertained by tri-annual questionnaires and a computerized
      dictionary used to categorize type of medication. RESULTS: In age-adjusted
      models, non-benzodiazepine sedative hypnotic use was associated with an increased
      risk of any falls (one or more falls) (RR 1.44, 95% CI 1.15, 1.81) and recurrent
      falls (2 or more falls) (RR 1.51, 95% CI 1.07, 2.14). Use of benzodiazepines was
      associated with a similar increase in age-adjusted risk of falling. Depressive
      symptoms, inability to stand from a chair, and instrumental activities of daily
      living (IADL) impairment modestly attenuated these associations. The association
      between non-benzodiazepine sedative-hypnotic use and falls was most pronounced
      among men without a history of falls in the previous year: in a multivariable
      model controlling for multiple potential confounders, the RR of any falls was
      1.74 (95% CI 1.13, 2.68) in this subgroup. CONCLUSIONS: Use of non-benzodiazepine
      sedative-hypnotics is associated with an increased risk of falls. Non
      pharmacologic approaches to sleep disturbances may represent the safest approach
      to sleep difficulties in older adults.

PMID- 25587491
TI  - Signaling Networks of Activated Oncogenic and Altered Tumor Suppressor Genes in
      Head and Neck Cancer.
AB  - Head and neck squamous cell carcinoma (HNSCC) arises from the upper aerodigestive
      tract and is the six most common cancers worldwide. HNSCC is associated with high
      morbidity and mortality, as standard surgery, radiation, and chemotherapy can
      cause significant disfigurement and only provide 5-year survival rates of ~50
      60%. The heterogeneity of HNSCC subsets with different potentials for recurrence
      and metastasis challenges the traditional pathological classification system,
      thereby increasing demand for the development of new diagnostic, prognostic, and
      therapeutic tools based on global molecular signatures of HNSCC. Historically,
      using classical biological techniques, it has been extremely difficult and time
      consuming to survey hundreds or thousands of genes in a given disease. However,
      the development of high throughput technologies and high-powered computation
      throughout the last two decades has enabled us to investigate hundreds or
      thousands of genes simultaneously. Using high throughput technologies, our
      laboratory has identified the gene signatures and protein networks, which
      significantly affect HNSCC malignant phenotypes, including TP53/p63/p73 family
      members, IL-1/TNF-beta/NF-kappaB, PI3K/AKT/mTOR, IL-6/IL-6R/JAK/STAT3,
      EGFR/MAPK/AP1, HGF/cMET/EGR1, and TGFbeta/TGFbetaR/TAK1/SMAD pathways. This
      review summarizes the results from high-throughput technological assays conducted
      on HNSCC samples, including microarray, DNA methylation, miRNA profiling, and
      protein array, using primarily experimental data and conclusions generated in our
      own laboratory. The use of bioinformatics and integrated analyses of data sets
      from different platforms, as well as meta-analysis of large datasets pulled from
      multiple publicly available studies, provided significantly higher statistical
      power to extract biologically relevant information. The data suggested that the
      heterogeneity of HNSCC genotype and phenotype are much more complex than we
      previously thought. Understanding of global molecular signatures and disease
      classification for specific subsets of HNSCC will be essential to provide
      accurate diagnoses for targeted therapy and personalized treatment, which is an
      important effort toward improving patient outcomes.

PMID- 25587495
TI  - Persistent Reduced Pigmentation of Areola after Breast Reconstruction with Brava
      assisted Autologeous Fat Grafting.
AB  - SUMMARY: A 17-year-old healthy woman treated for unilateral hypoplastic breast
      anomaly with Brava-assisted fat grafting experienced persistent reduced
      pigmentation of the areola on the treated breast. The reduced pigmentation was
      confirmed at 6-month postoperative follow-up and verified by histological
      examination of comparable biopsies from both areolas.

PMID- 25587494
TI  - Fat Graft Viability in the Subcutaneous Plane versus the Local Fat Pad.
AB  - BACKGROUND: Fat grafting has been increasingly utilized in both aesthetic and
      reconstructive surgical procedures, yet the basic scientific understanding of fat
      grafting has lagged behind the pace of clinical innovation and utilization. This
      lack of basic scientific understanding has perhaps manifested itself in the wide
      range of graft viability reported across the literature. This study attempts to
      further the underlying mechanisms of fat graft take and viability through the
      comparison of the subcutaneous plane and the local fat pad in athymic rats.
      METHODS: Lipoaspirate from a consenting patient was grafted into 2 locations in
      the subcutaneous plane and into the 2 inguinal fat pads in each of 4 athymic
      rats. Specimens were then collected after 47 days, and immunohistochemistry was
      utilized to determine angiogenesis in the fat grafts as a measure of fat graft
      take. Data were analyzed using the Student's t test and analysis of variance
      followed by multiple comparisons. RESULTS: There was no statistically significant
      difference (P = 0.2913) between the inguinal fat pad and the subcutaneous plane
      when measuring neovascularization. Analysis of variance comparing the graft
      locations also indicated no statistically significant difference when comparing
      each of the rats. CONCLUSIONS: Investigation into fat graft injection location
      indicates that there is no statistically significant difference in angiogenesis
      signals between the subcutaneous plane and the local fat pad in the athymic rat
      model. Further research should aim to continue to close the gap between clinical
      practice and basic scientific understanding of fat grafting.

PMID- 25587496
TI  - Wrist Tenosynovitis due to Mycobacterium bovis Infection: Case Series and Review
      of the Literature.
AB  - SUMMARY: Tuberculosis infections are still one of the most important public
      health problems among developing countries. Musculoskeletal involvement
      represents 10-15% of all extrapulmonary cases. Tuberculosis tenosynovitis is
      usually misdiagnosed as nonspecific tenosynovitis. To avoid misdiagnosis and
      mistreatment, it is important to be alert for mycobacterial infections. This
      article presents 3 patients with wrist tenosynovitis, which was caused by
      Mycobacterium bovis infection. The article also includes review of the
      literature.

PMID- 25587497
TI  - An Unusual Cause of Flexor Tenosynovitis: Streptococcus mitis.
AB  - SUMMARY: Streptococcus mitis is a commensal organism of the human oropharynx that
      rarely causes infection in healthy individuals. Herein, we describe a previously
      healthy 35-year-old woman who presented with acute pyogenic flexor tenosynovitis
      of the left index finger due to S. mitis infection. The patient's infection was
      treated successfully via surgical and medical interventions, and during follow
      up, it was determined that she was complement component C3 deficient.
      Tenosynovitis is an emergent clinical syndrome that can result in permanent
      disability or amputation. To the best of our knowledge, this case report is the
      first to describe tenosynovitis due to S. mitis; in addition, it highlights the
      importance of initiating therapy with antibiotics that are effective against this
      rare pathogen.

PMID- 25587498
TI  - A Case of Complex Facial Clefts Treated with Staged-tissue Expansion.
AB  - SUMMARY: Craniofacial clefts involve all soft tissue and skeletal elements
      throughout the cleft. Usefulness of tissue expansion in craniofacial clefts is
      reported. Surgery for a complex type of facial clefts is more difficult and more
      extensive than for a simple one. We experienced a primary case of complex facial
      clefts (Tessier No. 2 and 12 on the right and 3, 11, and 5 on the left). Soft
      tissue closure of all clefts could be completed by using 4 tissue expanders and 7
      operations. Because multiple tissue deficiencies and abnormalities exist in
      craniofacial clefts, especially complex type, a planned, staged, sequential
      approach by tissue expansion is necessary to produce ideal results.

PMID- 25587499
TI  - Inferior Turbinate Flap for Nasal-side Closure of Palatal Fistula in Cleft
      Patients: Technical Note.
AB  - SUMMARY: Residual palatal fistula after repair of palatal cleft is common. Repair
      of residual oronasal fistula is not always successful. Two-layer closure
      techniques that close these fistulas with soft tissue are a common practice.
      Turnover flaps are the most used flaps and often the sole method for nasal-side
      closure of fistula. Anteriorly based inferior turbinate flap can be used to
      provide soft tissue for nasal-side closure when turnover flaps will not provide
      sufficient tissue for this purpose. Under general anesthesia with nasotracheal
      intubation, inferior turbinate was released from posterior attachment. After
      removing the inferior conchal bone, mucoperiosteal flap was used for nasal-side
      closure of anterior palatal fistula in patients with cleft. Anteriorly based
      inferior turbinate flap was used for nasal-side closure of residual palatal
      fistula in 3 patients with cleft. Age of the patients was 14, 16, and 18, and
      recurrence of palatal fistula has not occurred. Anteriorly based inferior
      turbinate flap is an axial pattern flap with appropriate surface of the paddle
      and vicinity to the oral cavity roof. It can be used in large anterior, palatal
      fistula for reconstruction of nasal floor. Considering appropriate another flap
      for oral side coverage of such fistula is mandatory.

PMID- 25587501
TI  - Muscular pedicled lateral chest composite flap-a new nonmicrosurgical option for
      forearm salvage.
AB  - SUMMARY: Posttraumatic upper or lower limb salvage is still challenging. Under
      difficult situations in which only one vessel supplies the hand or foot, free
      microvascular reconstruction might damage not only the transferred tissue but
      also the terminal hand or foot. Two cases of incomplete amputation of the
      unilateral forearm with large radius bone and soft tissue loss were reconstructed
      using a newly-refined pedicled osteomyocutaneous flap including vascularized rib,
      lateral part of the latissimus dorsi muscle, and skin as a lateral chest flap.
      After insetting of the flap, the transferred limb is fixed with a soft bandage,
      and the flap is divided no less than 4 weeks after the first operation. The flap
      completely survived, and bone union between the rib and radius was observed.
      Although our treatment needed a two-stage procedure, safe and secure
      reconstruction with an appropriate amount of tissue for salvage was accomplished.

PMID- 25587500
TI  - Exclusion of musculature from the submental flap: a contingency plan for facial
      nerve palsy.
AB  - SUMMARY: Submental flap surgery is a useful and versatile reconstructive
      procedure. Currently, disagreement exists regarding the need to include the
      anterior belly of the digastric muscle or mylohyoid in the submental flap. The
      report outlines the value of excluding normal and variant anterior digastric and
      mylohyoid musculature from the submental flap as a contingency plan for marginal
      mandibular branch of facial nerve palsy. Also, the article addresses variant
      anterior digastric musculature, a common anatomical finding, as it relates to the
      submental flap. The question of whether or not to include the anterior digastric
      musculature does not necessitate an all-or-none decision. In the case of multiple
      anterior digastric bellies, some bellies may be included in the flap, whereas
      others are not. The location of the submental vessels and the desired bulk or
      contour of the flap should guide the decision of which anterior digastric
      bellies, if any, are included in the flap.

PMID- 25587502
TI  - Outcome studies in plastic surgery: knowing the objectives and avoiding pitfalls.

PMID- 25587503
TI  - The pinking shears: a novel tool for improving skin graft cosmesis.
AB  - SUMMARY: A significant aesthetic disadvantage to split skin grafts is the obvious
      transition between the graft and the normal skin. We report on a novel method to
      interrupt this transition point by using pinking shears, which are dressmaking
      scissors with saw-toothed blades that create a chevron pattern instead of a
      straight edge. We describe a case where the pinking shears were utilized on a
      split skin graft and Integra for reconstruction of the skin on a volar forearm.
      This technique allows for breaking-up of the transition point between the skin
      graft and normal skin and gives rise to an improved aesthetic outcome as the
      boundary is significantly less well-defined. This novel method shows promise and
      further study is certainly warranted.

PMID- 25587504
TI  - Severe Acute Radiodermatitis in a Keloid Patient with Takayasu's Arteritis.
AB  - SUMMARY: Although combination therapy for keloid including postoperative
      radiation therapy (RT) is common, the radiation toxicity of RT in a patient with
      a history of collagen vascular disease has not been fully recognized. We
      experienced a case of an acute radiodermatitis in a patient with keloid. This
      patient had a chest keloid because of the bypass surgery for Takayasu's
      arteritis. After we performed an excision and postoperative RT, severe
      radiodermatitis occurred. We speculate that the higher single dose and the use of
      electron beams may be related to the onset of severe acute radiodermatitis in
      this case. It should be kept in mind that there is a risk of exacerbation of
      radiation toxicity in patients with collagen vascular disease.

PMID- 25587505
TI  - The modifications of the sagittal ramus split osteotomy: a literature review.
AB  - BACKGROUND: In 1953, the sagittal ramus split osteotomy was introduced by
      Obwegeser. For many years, and in some countries still, this technique has
      defined the term oral and maxillofacial surgery. METHODS: The basic design of the
      sagittal ramus split surgical procedure evolved very quickly. The original
      operation technique by Obwegeser was shortly after improved by Dal Pont's
      modification. The second major improvement of the basic technique was added by
      Hunsuck in 1967. Since then, the technical and biological procedure has been well
      defined. Resolution of the problems many surgeons encountered has, however, taken
      longer. Some of these problems, such as the unfavorable split or the damage of
      the inferior alveolar nerve, have not been satisfactorily resolved. RESULTS:
      Further modifications, with or without the application of new instruments, have
      been introduced by Epker and Wolford, whose modification was recently elaborated
      by Bockmann. The addition of a fourth osteotomy at the inferior mandibular border
      in an in vitro experiment led to a significant reduction of the torque forces
      required for the mandibular split. CONCLUSIONS: The literature was reviewed, and
      the last modifications of the successful traditional splitting procedure are
      presented narrowly. It indicates the better the split is preformatted by
      osteotomies, the less torque force is needed while splitting, giving more
      controle, a better predictability of the lingual fracture and maybe less
      neurosensory disturbances of the inferior alveolar nerve.

PMID- 25587506
TI  - Nd:YAG Laser Treatment for Keloids and Hypertrophic Scars: An Analysis of 102
      Cases.
AB  - BACKGROUND: The present retrospective cohort study was performed to determine the
      efficacy of contact-mode 1064 nm neodymium-yttrium-aluminum-garnet (Nd:YAG) laser
      laser for keloids and hypertrophic scars. The indication and limitations of this
      modality are discussed. METHODS: The cohort consisted of 102 consecutive Japanese
      patients (23 males and 79 females) with keloids and hypertrophic scars for more
      than 1 year. They were treated every 3-4 weeks for 1 year with a long-pulsed 1064
      nm Nd:YAG laser (Cutera, Brisbane, Calif.) in contact mode. Thirty-eight patients
      had hypertrophic scars and 64 had keloids. The scars were evaluated before the
      treatment commenced and 1 month after the last session by using the Japan Scar
      Workshop Scar Scale 2011. Recurrence was assessed at 6 months after the
      termination of treatment. RESULTS: The average total Japan Scar Workshop score of
      the keloid and hypertrophic scar region groups dropped significantly after 1 year
      of treatment compared with before treatment (all P < 0.05). None of the
      hypertrophic scars or keloids deteriorated. However, 3 of the 34 anterior chest
      keloids (8.8%) did not respond. The following recurrence rates were observed 6
      months after stopping laser treatment: 1 of the abdomen hypertrophic scars (4%),
      18 of the anterior chest keloids (52.9%), 5 of the upper arm keloids (35.7%), and
      4 of the scapula keloids (25%). CONCLUSIONS: Hypertrophic scars responded
      significantly better to 1064 nm Nd:YAG laser treatment than keloids. However,
      keloid recurrence occurred when there was remaining redness and induration, even
      if only a small part of the scar was affected.

PMID- 25587507
TI  - A rare complication of septorhinoplasty.
AB  - SUMMARY: Septoplasty and septorhinoplasty are common procedures. A 28-year-old
      woman underwent the procedure and presented postoperatively with headache and
      vomiting and had developed a large pneumocephalus. We describe the case in detail
      and analyze the possible causes and ways to prevent such a complication.

PMID- 25587508
TI  - Innovative tactic in submandibular salivary gland partial resection.
AB  - SUMMARY: Adequate neck contour is one of the goals in facial rejuvenation. In
      some patients, treating the submandibular salivary gland (SMSG) ensures a
      satisfying result. Hematoma, sialoma, and paralysis of the depressors of the
      lower lip may occur when the deep neck is approached. The objective of this work
      is to present a new tactic to prevent the aforementioned complications. Two
      hundred forty consecutive neck lift patients with partial resection of the SMSG
      were studied. The tactic consisted of placing sutures to facilitate the
      retraction of the platysma muscle and the accompanying marginal mandibular and
      cervical branches of the facial nerve during the resection of the SMSG. It also
      included stitches that bring the platysma muscle in contact with the remaining
      SMSG, sealing the dissected area. The first 25 (control) subjects did not undergo
      the tactic; the remaining 215 (study group) did. The occurrence of paralysis of
      the depressors of the lower lip and of hematoma and sialoma originating from the
      SMSG resection was observed. When comparing the control group with the study
      group, the rates of hematoma (8% vs 0%) and sialoma (24% vs 0%) were
      significantly higher in the former. Paralysis of the depressors of the lower lip
      also had a higher rate in the control group (4% vs 0.9%) although this difference
      was not statistically significant. The surgical tactic described is efficient in
      preventing the occurrence of hematoma, sialoma, and paralysis of the depressors
      of the lower lip in neck lift with partial resection of the SMSG.

PMID- 25587510
TI  - Incidental Internal Mammary Nodes during Recipient Vessel Dissection in Breast
      Reconstruction: Are They Significant?
AB  - SUMMARY: Internal mammary (IM) lymph nodes may be exposed during recipient vessel
      preparation in free-flap breast reconstruction, and in rare cases, positivity of
      these nodes may affect treatment in patients with breast cancer. This systematic
      review examines the incidence and significance of IM nodes identified by plastic
      surgeons. Eligibility criteria included free-flap breast reconstruction with
      concurrent IM node biopsy. Data were analyzed for incidence of IM node biopsy and
      nodal positivity. Ten studies met inclusion criteria, with a total of 2055
      patients and 717 nodes submitted to pathology. Incidence of IM positivity ranged
      approximately from 1% to 11%, for a calculated gross overall incidence of 2.9%.
      Of 59 patients with a positive IM node, 50 patients received additional adjuvant
      therapy, with insufficient data to determine the effect of treatment on survival.

PMID- 25587511
TI  - Surgical Excision of Non-Melanoma Skin Cancer in an Elderly Veteran's Affairs
      Population.
AB  - BACKGROUND: Non-melanoma skin cancer (NMSC) is the most common malignancy in the
      United States. Recommended treatment for NMSC remains surgical excision following
      a positive biopsy. Evidence of complete spontaneous regression of residual NMSC
      exists in the case of small lesions macroscopically removed by shave biopsy, but
      with a positive microscopic margin. The present study investigates the rate at
      which residual tumor is present at subsequent excisional biopsy, with the aim to
      assess if recommendation to forgo surgical excision can be made. METHODS: A total
      of 233 shave biopsies of basal cell carcinoma (BCC) or squamous cell carcinoma
      (SCC) were performed during a 5-year period. All specimens included in the study
      were less than 2 cm in diameter, were macroscopically removed by shave biopsy,
      and had a positive initial microscopic margin. RESULTS: On subsequent surgical
      excisional biopsy, 42% of BCC specimens were negative for residual tumor, 38% had
      residual tumor, but the tumor was completely contained in the excised specimen,
      and 20% of the specimens had positive margin residual tumor. For SCC specimens,
      73% were negative for residual tumor, 21% had residual tumor, but the tumor was
      completely contained in the excised specimen, and 6% of the specimens had
      positive margin residual tumor. CONCLUSIONS: Although reduction of residual tumor
      at reexcision is noted with both BCC and even more so with SCC, the rate at which
      this occurs is not sufficient that a general recommendation to forgo surgical
      excision can be made.

PMID- 25587509
TI  - Fibromodulin Enhances Angiogenesis during Cutaneous Wound Healing.
AB  - BACKGROUND: Fibromodulin (FMOD) plays a critical role in the wound-healing
      process. Our previous studies revealed that FMOD deficiency led to marked
      alterations in adult wound healing characterized by delayed dermal cell
      migration, postponed wound closure, and increased scar formation, all accompanied
      by impeded angiogenesis. Therefore, the aim of this study was to reveal the
      effect of FMOD on angiogenesis during the wound-healing process. METHODS: In vivo
      angiogenic effects of FMOD were assessed by a chick embryo chorioallantoic
      membrane assay, a Matrigel (BD Bioscience, Franklin Lakes, N.J.) plug implant
      assay, and rodent primary closure wound models. In vitro angiogenic effects of
      FMOD were recorded by cell invasion and dimensional and topological parameters of
      human umbilical vein endothelial cells. RESULTS: We provided evidence that FMOD
      significantly enhanced vascularization: first, FMOD boosted blood vessel
      formation on the chorioallantoic membrane; second, FMOD markedly stimulated
      capillary infiltration into Matrigel plugs subcutaneously implanted in adult
      mice; and finally, FMOD robustly promoted angiogenesis in multiple adult rodent
      cutaneous wound models. Furthermore, FMOD administration restored the vascularity
      of fmod (-/-) mouse wounds. In support of this, FMOD endorsed an angiogenesis
      favored microenvironment in adult rodent wounds not only by upregulating
      angiogenic genes but also by downregulating angiostatic genes. In addition, FMOD
      significantly enhanced human umbilical vein endothelial cell invasion and tube
      like structure formation in vitro. CONCLUSIONS: Altogether, we demonstrated that
      in addition to reducing scar formation, FMOD also promotes angiogenesis. As blood
      vessels organize and regulate wound healing, its potent angiogenic properties
      will further expand the clinical application of FMOD for cutaneous healing of
      poorly vascularized wounds.

PMID- 25587512
TI  - The Rationale for Treating the Nodule in Dupuytren's Disease.
AB  - BACKGROUND: Dupuytren's disease encompasses a spectrum of fibroblastic disorders
      from the presence of 1-2 nodules in the palm of a hand with no joint contracture
      to grotesque, crippling and disabling deformities of hands. Over the last 50
      years, many enlightening studies have been forthcoming, which, through techniques
      of histopathology, biochemistry, tissue culture, and electron microscopy, have
      shed pearls of light on various aspects of the disease process. METHODS: A
      comprehensive review of the literature on Dupuytren's disease was undertaken,
      stringing together results from numerous studies to establish a table of events
      and their location in the development of the disease. RESULTS: What will be seen
      is a credible scenario of events which will enable the clinician to be more
      proactive in the earlier treatment of the disease and more aware of factors that
      increase or decrease recurrence rates postoperatively. CONCLUSIONS: The most
      effective management of Dupuytren's disease is early recognition and treatment of
      the nodule, before the development of a joint contracture, particularly of a
      proximal interphalangeal joint. As there is evidence of a significant
      inflammatory role in the development of the nodule, the process of fibroplasia
      can be minimized by altering the macrophage > fibroblast > collagen cascade by
      the intralesional injection of a potent anti-inflammatory agent such as
      triamcinolone, which also blocks tissue inhibitors of collagenase, thus enhancing
      the action of native collagenase, and reduces the size and firmness of nodules
      and, at least temporarily, arrests their progression.

PMID- 25587513
TI  - Reply: the limitations of psychometric outcome studies in plastic surgery.

PMID- 25587514
TI  - Psychometrics: Essential for Valid, Reliable, and Responsive Measurement in the
      Development of Patient-reported Outcome Instruments in Plastic Surgery.

PMID- 25587515
TI  - Breast Reduction versus Breast Reduction Plus Implants: A Comparative Study with
      Measurements and Outcomes.
AB  - BACKGROUND: Breast reduction is well-known to provide an improvement in physical
      symptoms. However, measurements show that this procedure is less effective in
      restoring upper-pole fullness. Breast implants effectively augment the upper
      pole. This study was undertaken to determine the effectiveness and safety of this
      treatment combination. METHODS: This retrospective study consists of 3 parts: (1)
      a clinical study, (2) breast measurements, and (3) an outcome study. Eighty
      consecutive women undergoing breast reduction (n = 56) or breast reduction plus
      implants (n = 24) were evaluated. All breast implants were inserted
      submuscularly. All patients were treated with the same vertical reduction
      technique, using a medially based pedicle and intraoperative nipple positioning.
      Measurements were compared between preoperative photographs and photographs taken
      at least 3 months after surgery (n = 51). Patient surveys (n= 56) were evaluated.
      RESULTS: There was no significant difference in complication or reoperation rates
      between groups. Both procedures elevated the breast mound and lower-pole level
      and increased the breast parenchymal ratio (upper-pole area/lower-pole area).
      Breast implants significantly increased upper-pole projection (P < 0.01). All
      surveyed patients who had simultaneous implants reported that they were pleased
      with their decision. Physical symptoms were reduced in both groups. Patient
      satisfaction was 92.5% for breast reduction and 93.8% for breast reduction plus
      implants. Both groups reported an improvement in quality of life. CONCLUSIONS:
      Vertical breast reduction with a medial pedicle may be combined safely and
      effectively with breast implants in patients who desire upper-pole fullness.

PMID- 25587516
TI  - Medial and lateral pectoral nerve block with liposomal bupivacaine for the
      management of postsurgical pain after submuscular breast augmentation.
AB  - SUMMARY: This report describes an ultrasound-guided medial and lateral pectoralis
      nerve block using liposome bupivacaine, performed before the surgical incision,
      in a patient undergoing submuscular breast augmentation. The anatomic basis and
      technique are described. This procedure may be offered to patients undergoing
      submuscular insertion of a breast implant or tissue expander. Advancements in
      ultrasound guidance allow for more precise anatomic placement of local anesthetic
      agents. The injection technique used for this procedure resulted in complete
      relaxation of the pectoralis major, facilitating the surgical dissection and
      markedly diminishing postsurgical pain and muscle spasms.

PMID- 25587517
TI  - Gold Nanoparticle-assisted Selective Photothermolysis of Adipose Tissue
      (NanoLipo).
AB  - BACKGROUND: Conventional suction-assisted lipectomy (SAL) often results in
      contour irregularity. Selective photothermal heating of adipose tissue by polymer
      coated gold nanorods energized by an external near-infrared exposure at 800 nm is
      introduced in this work to facilitate fat removal. METHODS: The effects of
      NanoLipo were examined in food-grade porcine abdominal tissue (skin, fat, and
      fascia) by histology. The efficacy of NanoLipo was compared with that of
      conventional SAL in vivo in Yucatan mini pigs by quantification of removed
      subcutaneous tissue and fatty acids and ultrasound measurement of adipose layer
      thickness. RESULTS: NanoLipo led to the appearance of disruptions in adipose
      tissue that were not apparent in control groups in ex vivo samples. NanoLipo
      allowed removal of more subcutaneous tissue (~33% vs ~25% of removed material, P
      < 0.05) and approximately twice as much free fatty acids (~60% vs ~30% of removed
      tissue, P < 0.05) in comparison with conventional SAL. Most importantly, NanoLipo
      led to a greater decrease in adipose layer thickness at 1 month post surgery (P <
      0.001). CONCLUSIONS: NanoLipo facilitates removal of a greater quantity of fat
      and requires less suction time (4 vs 10 minutes) than conventional SAL. As the
      safety of poly(ethylene-glycol)-coated gold nanorods is well-established, a
      clinical trial is currently being organized.

PMID- 25587518
TI  - Models of Care in Geriatric Oncology.
AB  - Cancer is common in older adults and the approach to cancer treatment and
      supportive measures in this age group is continuously evolving. Incorporating
      geriatric assessment (GA) into the care of the older patient with cancer has been
      shown to be feasible and predictive of outcomes, and there are unique aspects of
      the traditional geriatric domains that can be considered in this population.
      Geriatric assessment-guided interventions can also be developed to support
      patients during their treatment course. There are several existing models of
      incorporating geriatrics into oncology care, including a consultative geriatric
      assessment, geriatrician "embedded" within an oncology clinic and primary
      management by a dual-trained geriatric oncologist. Although a geriatrician or
      geriatric oncologist leads the geriatric assessment, is it truly a
      multidisciplinary assessment, and often includes evaluation by a physical
      therapist, occupational therapist, pharmacist, social worker and nutritionist.

PMID- 25587519
TI  - Diets for constipation.
AB  - Chronic constipation is a very common disease in children. Successful treatment
      of constipation can be achieved not only with medication but also with lifestyle
      changes, including a proper diet. Diets including fruits, fluids, and probiotics
      are good for constipation. Some dietary components are helpful for constipation,
      and some are harmful. In this study, we present diets related to constipation
      from the literature, and propose some perspectives regarding diets related to
      constipation. 

PMID- 25587521
TI  - Short-Term Complications of Percutaneous Endoscopic Gastrostomy according to the
      Type of Technique.
AB  - PURPOSE: The method of percutaneous endoscopic gastrostomy (PEG) tube placement
      can be divided into the pull and introducer techniques. We compared short-term
      complications and prognosis between patients who underwent the pull technique and
      two other types of introducer techniques, the trocar introducer technique and T
      fastener gastropexy technique. METHODS: Twenty-six patients who underwent PEG
      were enrolled in this study. We retrospectively investigated the age, sex, body
      weight, weight-for-age Z-score, underlying diseases, PEG indications,
      complications, duration of NPO (nil per os), pain control frequency, and duration
      of antibiotic therapy. The patients were classified into three groups according
      to the PEG technique. The occurrence of complications was monitored for 10 weeks
      after the procedure. RESULTS: The age, sex, body weight, and weight-for-age Z
      score were not significantly between the three groups. Most patients had cerebral
      palsy and seizure disorders. Dysphagia was the most common indication for PEG.
      Major complications occurred in 5 (50%), 4 (66.7%), and 0 (0%) patients in group
      I, II, and III, respectively (p=0.005). Further, peristomal infection requiring
      systemic antibiotic therapy occurred in 2 (20%), 3 (50%), and 0 (0%) patients in
      group I, II, and III, respectively (p=0.04). There was no significant difference
      between the groups with respect to minor complications, duration of NPO, pain
      control frequency, and duration of antibiotic therapy. CONCLUSION: The results
      indicate that the T-fastener gastropexy technique was associated with the lowest
      rate of major complications.

PMID- 25587520
TI  - Clonazepam treatment of pathologic aerophagia in children with mental
      retardation.
AB  - PURPOSE: Pathologic aerophagia (PA) may lead to bowel perforation or volvulus in
      mentally retarded patients. The authors investigated the effects of clonazepam on
      the management of PA in children with severe to profound mental retardation (MR).
      METHODS: This study was undertaken as a retrospective case analysis of 21 PA
      patients with MR who were followed for over 12 months and diagnosed as having PA.
      Patients were assigned to two management groups, that is, to a clonazepam
      randomized open-labeled, treatment group or a reassurance group. The following
      were recorded and analyzed; age, response, remission rate to clonazepam
      treatment, and the side effect of clonazepam. It was defined positive response
      (response+) as being symptom-free for a whole week within 1 month of commencing
      treatment and remission(+) as being symptom-free for a whole month within 6
      months of treatment. RESULTS: The average age of the 21 PA children with MR was
      10 years and 13 patients were female. Symptom duration before diagnosis of PA was
      7 months. Clinical features of the clonazepam-trial group (n=11) and the
      reassurance group (n=10) were non-significantly different. Response(+) was
      achieved by 2 patients (18.2%) in the clonazepam-trial group and by no patient in
      the reassurance group. Remission(+) was achieved by 6 patients (54.5%) in the
      clonazepam-trial group and by one patient (10%) in the reassurance group
      (p=0.040). CONCLUSION: When PA children with MR with severe bowel distention are
      considered for surgical treatment to prevent acute abdomen, a trial of clonazepam
      could be recommended.

PMID- 25587522
TI  - Systemic classification for a new diagnostic approach to acute abdominal pain in
      children.
AB  - PURPOSE: With previous methods based on only age and location, there are many
      difficulties in identifying the etiology of acute abdominal pain in children. We
      sought to develop a new systematic classification of acute abdominal pain and to
      give some helps to physicians encountering difficulties in diagnoses. METHODS:
      From March 2005 to May 2010, clinical data were collected retrospectively from
      442 children hospitalized due to acute abdominal pain with no apparent underlying
      disease. According to the final diagnoses, diseases that caused acute abdominal
      pain were classified into nine groups. RESULTS: The nine groups were group I
      "catastrophic surgical abdomen" (7 patients, 1.6%), group II "acute appendicitis
      and mesenteric lymphadenitis" (56 patients, 12.7%), group III "intestinal
      obstruction" (57 patients, 12.9%), group IV "viral and bacterial acute
      gastroenteritis" (90 patients, 20.4%), group V "peptic ulcer and
      gastroduodenitis" (66 patients, 14.9%), group VI "hepatobiliary and pancreatic
      disease" (14 patients, 3.2%), group VII "febrile viral illness and
      extraintestinal infection" (69 patients, 15.6%), group VIII "functional
      gastrointestinal disorder (acute manifestation)" (20 patients, 4.5%), and group
      IX "unclassified acute abdominal pain" (63 patients, 14.3%). Four patients were
      enrolled in two disease groups each. CONCLUSION: Patients were distributed
      unevenly across the nine groups of acute abdominal pain. In particular, the
      "unclassified abdominal pain" only group was not uncommon. Considering a systemic
      classification for acute abdominal pain may be helpful in the diagnostic approach
      in children.

PMID- 25587523
TI  - Clinical Characteristics of Symptomatic Clostridium difficile Infection in
      Children: Conditions as Infection Risks and Whether Probiotics Is Effective.
AB  - PURPOSE: This study investigated the clinical presentations of symptomatic
      Clostridium difficile infection (CDI) in children. METHODS: We reviewed the
      medical records of 43 children aged <20 years who showed either positive C.
      difficile culture or C. difficile toxin test results between June 2010 and April
      2014. RESULTS: Of the 43 patients (mean age 6.7 years), 22 were boys. Sixteen
      patients (37.2%) showed both positive C. difficile culture and toxin test
      results. Seventeen out of 43 children (39.5%) had preexisting gastrointestinal
      diseases, and 26 children had other medical conditions that were risk factors for
      CDI. Twenty-eight children had a history of antibiotic treatment for >3 days, and
      the most frequently prescribed antibiotic was amoxicillin-clavulanate (35.7%).
      Twenty-eight patients were diagnosed with CDI despite taking probiotic
      supplements, most commonly Lactobacillus acidophilus (53.6%). The most common
      symptom was diarrhea (72.1%) at the time CDI was diagnosed. C. difficile was
      eradicated in 11 patients (25.6%) after treatment with oral metronidazole for 10
      14 days, and in the two patients (4.6%) who required two courses of oral
      metronidazole. Sixteen patients (37.2%) showed clinical improvement without any
      treatment. CONCLUSION: This study showed the various clinical characteristics of
      CDI in children and that preexisting clinical conditions favored the development
      of CDI. In addition, CDI was found to occur in a number of patients even after
      probiotic prophylaxis given in conjunction with antibiotic therapy.

PMID- 25587525
TI  - The clinical significance of serum ferritin in pediatric non-alcoholic Fatty
      liver disease.
AB  - PURPOSE: Non-alcoholic fatty liver disease (NAFLD) in children has become an
      important public health issue because of its high prevalence and severity.
      Several noninvasive methods for estimating NAFLD are under investigation. We
      aimed to evaluate the usefulness of serum ferritin as a biomarker of severity of
      pediatric NAFLD patients. METHODS: A total of 64 NAFLD patient were enrolled from
      Severance Children's Hospital from March 2010 to February 2013. Serum ferritin
      levels, liver related laboratory tests, liver magnetic resonance imaging (MRI) (2
      dimensional [2D] proton density-fat fraction) and NAFLD severity markers were
      compared between obese group and overweight group. Correlation analyses were
      performed between serum ferritin and laboratory values including NAFLD severity
      markers. RESULTS: In obese group, serum ferritin, alanine aminotransferase (ALT),
      total bilirubin, international normalized ratio (INR), MRI 2D proton density-fat
      fraction, aspartate aminotransferase (AST) to platelet ratio index (APRI) and
      fibrosis-4 (FIB-4) (an index score calculated from platelet count, ALT, AST and
      age) were significantly higher than those of overweight group. NAFLD severity
      markers, APRI and FIB-4, and liver specific important laboratory values, AST,
      ALT, INR, cholesterol, triglyceride and low density lipoprotein show significant
      correlation with serum ferritin in NAFLD patients. CONCLUSION: Serum ferritin
      concentrations could be a candidate of useful severity marker in the pediatric
      NAFLD patients.

PMID- 25587524
TI  - Does type I truly dominate hepatic glycogen storage diseases in Korea?: a single
      center study.
AB  - PURPOSE: There are no studies of hepatic glycogen storage diseases (GSDs) other
      than type I and III in Korea. We aimed on investigating the characteristics of
      hepatic GSDs in Korea diagnosed and followed at a single center. METHODS: We
      retrospectively analyzed patients who were diagnosed as GSD and followed at
      Samsung Medical Center from January, 1997 to December, 2013. Clinical
      manifestations, laboratory results, treatment, and prognosis were investigated.
      RESULTS: Twenty-one patients were included in the study. The types of 17 patients
      were confirmed by enzyme activity tests and/or gene analysis. GSD Ia was
      diagnosed in 7 patients (33.3%), Ib in 1 patient (4.8%), III in 2 patients
      (9.5%), IV in 1 patient (4.8%), and IX in 6 patients (28.6%). Types other than
      GSD I constituted 52.9% (9/17) of the patients diagnosed with a specific type of
      hepatic GSD. The median age at presentation was 2 years. Hepatomegaly was
      observed in 95.2%, elevated liver transaminases in 90.5%, and hyperlactacidemia
      in 81.0% of the patients. The duration for follow-up was 77+/-62.0 months.
      Uncooked corn starch was initiated in all the patients. No mortality was observed
      during the follow-up period, and liver transplantation was performed in 14.3%.
      CONCLUSION: Types other than GSD I comprised more than half of the patients
      diagnosed with a specific type of hepatic GSD. Clinical suspicion and thorough
      evaluation of hepatic GSDs in Korea should be focused not only on GSD I, but also
      on other types.

PMID- 25587526
TI  - The complex surgical management of the first case of severe combined
      immunodeficiency and multiple intestinal atresias surviving after the fourth year
      of life.
AB  - Severe combined immunodeficiency (SCID) is a life-threatening syndrome of
      recurrent infections and gastrointestinal alterations due to severe compromise of
      T cells and B cells. Clinically, most patients present symptoms before the age of
      3 months and without intervention SCID usually results in severe infections and
      death by the age of 2 years. Its association with intestinal anomalies as
      multiple intestinal atresias (MIA) is rare and worsens the prognosis, resulting
      lethal. We describe the case of a four year-old boy with SCID-MIA. He presented
      at birth with meconium peritonitis, multiple ileal atresias and underwent several
      intestinal resections. A targeted Sanger sequencing revealed a homozygous 4-bp
      deletion (c.313DeltaTATC; p.Y105fs) in tetratricopeptide repeat domain 7A
      (TTC7A). He experienced surgical procedures including resection and
      stricturoplasty. Despite parenteral nutrition-associated liver disease, the
      patient is surviving at the time of writing the report. Precocious immune system
      assessment, scrutiny of TTC7A mutations and prompt surgical procedures are
      crucial in the management. 

PMID- 25587527
TI  - A case of epiploic appendagitis with acute gastroenteritis.
AB  - Epiploic appendagitis is an inflammation of the epiploic appendage in which the
      small sacs projecting from the serosal layer of the colon are positioned
      longitudinally from the caecum to the rectosigmoid area. Epiploic appendagitis is
      rare and self-limiting; however, it can cause sudden abdominal pain in children.
      Epiploic appendagitis does not typically accompany other gastrointestinal
      diseases. Here, we report on a healthy eight-year-old girl who presented with
      abdominal pain, fever, vomiting, and diarrhea. Based on these symptoms, she was
      diagnosed with acute gastroenteritis, but epiploic appendagitis in the ascending
      colon was revealed in contrast computed tomography (CT). The patient was treated
      successfully with conservative management. CT is beneficial in diagnosis and
      further assessment of epiploic appendagitis. Pediatricians need to be aware of
      this self-limiting disease and consider it as a possible alternate diagnosis in
      cases of acute abdominal pain. 

PMID- 25587528
TI  - Coexistence of gilbert syndrome and hereditary spherocytosis in a child
      presenting with extreme jaundice.
AB  - Gilbert syndrome is the most common inherited disorder of bilirubin
      glucuronidation. It is characterized by intermittent episodes of jaundice in the
      absence of hepatocellular disease or hemolysis. Hereditary spherocytosis is the
      most common inherited hemolytic anemia and is characterized by spherical,
      osmotically fragile erythrocytes that are selectively trapped by the spleen. The
      patients have variable degrees of anemia, jaundice, and splenomegaly. Hereditary
      spherocytosis usually leads to mild-to-moderate elevation of serum bilirubin
      levels. Severe hyperbilirubinemia compared with the degree of hemolysis should be
      lead to suspicion of additional clinical conditions such as Gilbert syndrome or
      thalassemia. We present the case of a 12-year-old boy with extreme jaundice and
      nausea. The diagnosis of hereditary spherocytosis was confirmed by osmotic
      fragility test results and that of Gilbert syndrome by genetic analysis findings.

PMID- 25587530
TI  - Peripheral nerve regeneration: mechanism, cell biology, and therapies.

PMID- 25587529
TI  - The potential utility of pharmacogenetic testing in psychiatry.
AB  - Over the last decade, pharmacogenetics has become increasingly significant to
      clinical practice. Psychiatric patients, in particular, may benefit from
      pharmacogenetic testing as many of the psychotropic medications prescribed in
      practice lead to varied response rates and a wide range of side effects. The use
      of pharmacogenetic testing can help tailor psychotropic treatment and inform
      personalized treatment plans with the highest likelihood of success. Recently,
      many studies have been published demonstrating improved patient outcomes and
      decreased healthcare costs for psychiatric patients who utilize genetic testing.
      This review will describe evidence supporting the clinical utility of genetic
      testing in psychiatry, present several case studies to demonstrate use in
      everyday practice, and explore current patient and clinician opinions of genetic
      testing. 

PMID- 25587531
TI  - Proteoglycans/glycosaminoglycans: from basic research to clinical practice.

PMID- 25587533
TI  - Performance analysis of extracted rule-base multivariable type-2 self-organizing
      fuzzy logic controller applied to anesthesia.
AB  - We compare type-1 and type-2 self-organizing fuzzy logic controller (SOFLC) using
      expert initialized and pretrained extracted rule-bases applied to automatic
      control of anaesthesia during surgery. We perform experimental simulations using
      a nonfixed patient model and signal noise to account for environmental and
      patient drug interaction uncertainties. The simulations evaluate the performance
      of the SOFLCs in their ability to control anesthetic delivery rates for
      maintaining desired physiological set points for muscle relaxation and blood
      pressure during a multistage surgical procedure. The performances of the SOFLCs
      are evaluated by measuring the steady state errors and control stabilities which
      indicate the accuracy and precision of control task. Two sets of comparisons
      based on using expert derived and extracted rule-bases are implemented as
      Wilcoxon signed-rank tests. Results indicate that type-2 SOFLCs outperform type-1
      SOFLC while handling the various sources of uncertainties. SOFLCs using the
      extracted rules are also shown to outperform those using expert derived rules in
      terms of improved control stability. 

PMID- 25587534
TI  - Imaging neurodegenerative diseases: mechanisms and interventions.

PMID- 25587535
TI  - Radiopharmaceuticals in nuclear medicine: recent developments for SPECT and PET
      studies.

PMID- 25587532
TI  - Cysteine cathepsin activity regulation by glycosaminoglycans.
AB  - Cysteine cathepsins are a group of enzymes normally found in the endolysosomes
      where they are primarily involved in intracellular protein turnover but also have
      a critical role in MHC II-mediated antigen processing and presentation. However,
      in a number of pathologies cysteine cathepsins were found to be heavily
      upregulated and secreted into extracellular milieu, where they were found to
      degrade a number of extracellular proteins. A major role in modulating cathepsin
      activities play glycosaminoglycans, which were found not only to facilitate their
      autocatalytic activation including at neutral pH, but also to critically modulate
      their activities such as in the case of the collagenolytic activity of cathepsin
      K. The interaction between cathepsins and glycosaminoglycans will be discussed in
      more detail. 

PMID- 25587536
TI  - Current and future novel treatments for glioblastoma multiforme.

PMID- 25587537
TI  - The tumor microenvironment and cancer.

PMID- 25587538
TI  - Advances in molecular pathway-directed cancer systems imaging and therapy.

PMID- 25587539
TI  - Ovarian cancer.

PMID- 25587540
TI  - Parasites: from source to vector and human.

PMID- 25587541
TI  - Biomarkers of environmental pollutants.

PMID- 25587542
TI  - High-performance computing and big data in omics-based medicine.

PMID- 25587543
TI  - T-cell cytokine gene polymorphisms and vitamin D pathway gene polymorphisms in
      end-stage renal disease due to type 2 diabetes mellitus nephropathy: comparisons
      with health status and other main causes of end-stage renal disease.
AB  - BACKGROUND: T-cell cytokine gene polymorphisms and vitamin D pathway gene
      polymorphisms were evaluated as possibly associated with end-stage renal disease
      (ESRD) resulting from type 2 diabetes mellitus (DM) nephropathy. METHODS: Studies
      were conducted among hemodialysis (HD) patients with ESRD due to type 2 DM
      nephropathy, chronic glomerulonephritis, chronic infective tubulointerstitial
      nephritis, and hypertensive nephropathy as well as in healthy subjects. A
      frequency distribution of T-cell-related interleukin (IL) genes (IL18 rs360719,
      IL12A rs568408, IL12B rs3212227, IL4R rs1805015, IL13 rs20541, IL28B rs8099917,
      IL28B, and rs12979860) and vitamin D pathway genes (GC genes: rs2298849, rs7041,
      and rs1155563; VDR genes: rs2228570, rs1544410; and RXRA genes: rs10776909,
      rs10881578, and rs749759) was compared between groups. RESULTS: No significant
      differences in a frequency distribution of tested polymorphisms were shown
      between type 2 DM nephropathy patients and controls. A difference was found in
      IL18 rs360719 polymorphic distribution between the former group and chronic
      infective tubulointerstitial nephritic patients (P trend = 0.033), which also
      differed in this polymorphism from controls (P trend = 0.005). CONCLUSION: T-cell
      cytokine and vitamin D pathway gene polymorphisms are not associated with ESRD
      due to type 2 DM nephropathy in Polish HD patients. IL18 rs360719 is probably
      associated with the pathogenesis of chronic infective tubulointerstitial
      nephritis.

PMID- 25587544
TI  - TNF-alpha and microalbuminuria in patients with type 2 diabetes mellitus.
AB  - AIM: Recent evidence suggests that chronic subclinical inflammation plays a key
      role in the pathogenesis and progression of diabetic nephropathy. Aim of the
      present study was to investigate possible correlation between the presence and
      degree of microalbuminuria and markers of inflammation in patients with type 2
      diabetes mellitus (DM). PATIENTS-METHODS: Eighty patients were enrolled and
      clinical and laboratory data were recorded. Albumin-creatinine ratio (ACR) was
      calculated in first-morning urine samples. Serum and urinary tumor necrosis
      factor-alpha (TNF-alpha) levels were determined by ELISA. RESULTS: Forty-five
      patients had normoalbuminuria, 33 microalbuminuria, and 2 macroalbuminuria.
      Patients with microalbuminuria were older, with higher glycosylated hemoglobin
      levels (HbA1c) and they more frequently had diabetic retinopathy, neuropathy, and
      cardiovascular disease and were on treatment with angiotensin converting enzyme
      inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs). ACR was
      significantly correlated with the presence of cardiovascular disease,
      hypertension, and HbA1c levels and the administration of clopidogrel and ACEi or
      ARBs. ACR was not correlated with C-reactive protein, fibrinogen, or serum TNF
      alpha levels but had a strong correlation with urinary TNF-alpha levels.
      CONCLUSIONS: In patients with type 2 DM, urinary, but not serum, TNF-alpha levels
      are associated with the presence and severity of microalbuminuria.

PMID- 25587545
TI  - Generating and reversing chronic wounds in diabetic mice by manipulating wound
      redox parameters.
AB  - By 2025, more than 500 M people worldwide will suffer from diabetes; 125 M will
      develop foot ulcer(s) and 20 M will undergo an amputation, creating a major
      health problem. Understanding how these wounds become chronic will provide
      insights to reverse chronicity. We hypothesized that oxidative stress (OS) in
      wounds is a critical component for generation of chronicity. We used the db/db
      mouse model of impaired healing and inhibited, at time of injury, two major
      antioxidant enzymes, catalase and glutathione peroxidase, creating high OS in the
      wounds. This was necessary and sufficient to trigger wounds to become chronic.
      The wounds initially contained a polymicrobial community that with time selected
      for specific biofilm-forming bacteria. To reverse chronicity we treated the
      wounds with the antioxidants alpha-tocopherol and N-acetylcysteine and found that
      OS was highly reduced, biofilms had increased sensitivity to antibiotics, and
      granulation tissue was formed with proper collagen deposition and remodeling. We
      show for the first time generation of chronic wounds in which biofilm develops
      spontaneously, illustrating importance of early and continued redox imbalance
      coupled with the presence of biofilm in development of wound chronicity. This
      model will help decipher additional mechanisms and potentially better diagnosis
      of chronicity and treatment of human chronic wounds.

PMID- 25587546
TI  - ACE insertion/deletion polymorphism and diabetic nephropathy: clinical
      implications of genetic information.
AB  - Approximately 20-40% of diabetic patients develop nephropathy which is the
      leading cause of ESRD in developed countries. The ACE I/D polymorphism is thought
      to be a marker for functional polymorphism which regulates circulating and tissue
      ACE activity. While the initial study found a protective effect of the II
      genotype on the development of nephropathy in IDDM patients, subsequent studies
      have addressed the role of ACE I/D polymorphism in the development and
      progression of diabetic nephropathy. RAAS blockers are the first line drugs for
      the treatment hypertension associated with diabetes and have been widely used in
      everyday clinical practice for the purpose of reducing proteinuria in patients
      with various renal diseases. However, the antiproteinuric effect of RAAS blockers
      is variable and the percentage of reducing proteinuria is in the range of 20-80%.
      The antiproteinuric effect of RAAS blockers may be related to a number of
      factors: the type or the dose of RAAS blockers, the duration of therapy, the
      level of sodium intake, and the type of patient's ACE I/D genotype. Besides the
      nongenetic factors, drug responses, can be influenced by ACE gene polymorphism.
      In this review, we discuss the relationship between ACE I/D polymorphism and
      diabetic nephropathy and therapeutic response of RAAS blockers. 

PMID- 25587548
TI  - Needs assessment and evaluation of a short course to improve faculties teaching
      skills at a former World Health Organization regional teacher training center.
AB  - INTRODUCTION: In the design of educational programs, much attention has been paid
      to teaching methods, needs assessment, an important part of the development of
      educational programs, generally is neglected. Another important aspect in
      educational program design is assessing effectiveness. The aims of this study
      were to design a formal needs assessment program to define the core contents of a
      faculty development program, and to determine whether participation in the
      faculty development program reinforced new teaching skills. METHODS: A teacher
      training program was designed at Shiraz University of Medical Sciences to help
      medical instructors boost their teaching skills. Needs assessment was done with
      nominal group technique followed by a 5-point Likert scale questionnaire. The
      program, imparted in workshop format, covered effective teaching methods,
      feedback, assessing knowledge and time management. Instruction was in the form of
      lectures, group discussions, case simulations, video presentations and role
      plays. The program was evaluated in several phases using data triangulation and
      multi-item assessments of overall program quality in three major dimensions:
      Kirkpatrick program evaluation model, evaluation of the educational environment
      and qualitative analysis with open-ended questions. All participants in the study
      belonged to the academic staff of Shiraz University of Medical Sciences (n=396).
      RESULTS: Seven main categories were derived from nominal group techniques and
      questionnaires. After the program, participants rated the quality of the program
      highly. They felt that the educational intervention was appropriate and had a
      positive impact on their knowledge of effective teaching methods, feedback,
      knowledge assessment and time management. Assessment of the effectiveness of the
      program showed that participants reported significant improvements in their
      teaching abilities. CONCLUSIONS: Our faculty development program  have a
      significant positive effect on medical university teaching staff members'
      competencies. Further research is needed to investigate whether the faculty
      development program actually results in improved teaching performance.

PMID- 25587547
TI  - Relationship between levels of brain-derived neurotrophic factor and metabolic
      parameters in patients with type 2 diabetes mellitus.
AB  - BACKGROUND AND AIM: Studies have suggested that brain-derived neurotrophic factor
      (BDNF) plays a role in glucose and lipid metabolism and inflammation. The aim of
      this study was to evaluate the relationship between serum BDNF levels and various
      metabolic parameters and inflammatory markers in patients with type 2 diabetes
      mellitus (T2DM). MATERIALS AND METHODS: The study included 88 T2DM patients and
      33 healthy controls. Fasting blood samples were obtained from the patients and
      the control group. The serum levels of BDNF were measured with an ELISA kit. The
      current paper introduces a receiver-operating characteristic (ROC) generalization
      curve to identify cut-off for the BDNF values in type 2 diabetes patients.
      RESULTS: The serum levels of BDNF were significantly higher in T2DM patients than
      in the healthy controls (206.81 +/- 107.32 pg/mL versus 130.84 +/- 59.81 pg/mL; P
      < 0.001). They showed a positive correlation with the homeostasis model
      assessment of insulin resistance (HOMA-IR) (r = 0.28; P < 0.05), the triglyceride
      level (r = 0.265; P < 0.05), and white blood cell (WBC) count (r = 0.35; P <
      0.001). In logistic regression analysis, age (P < 0.05), body mass index (BMI) (P
      < 0.05), C-reactive protein (CRP) (P < 0.05), and BDNF (P < 0.01) were
      independently associated with T2DM. In ROC curve analysis, BDNF cut-off was 137.
      CONCLUSION: The serum BDNF level was higher in patients with T2DM. The BDNF had a
      cut-off value of 137. The findings suggest that BDNF may contribute to glucose
      and lipid metabolism and inflammation.

PMID- 25587549
TI  - Impact of media literacy education on knowledge and behavioral intention of
      adolescents in dealing with media messages according to Stages of Change.
AB  - INTRODUCTION: Mass media influence the health behaviors of adolescents. Evidence
      shows that traditional strategies such as censorship or limitation are no longer
      efficient; therefore, teaching media literacy is the best way to protect
      adolescents from harmful effects. The aim of this pilot study was to evaluate the
      effects of a media literacy training program on knowledge and behavioral
      intention of a sample of female students according to the stages of change in
      dealing with media messages. METHODS: The study was conducted based on a pre-test
      and post-test control group design. Some 198 female students including 101 in the
      intervention group and 97 in the control group participated in this study. The
      educational program was run using interactive teaching-learning techniques. Data
      collection was performed using a validated and reliable self-administered
      questionnaire in three phases including a pre-test, post-test, 1 and post-test,
      2. The research data was analyzed through SPSS statistical software, version 14
      using both descriptive and inferential statistics. RESULTS: The results of the
      study showed a significant increase (p=0.001) in the intervention group's
      knowledge mean scores after the training program. On the other hand, the
      difference was not significant in the control group (p=0.200). A considerable
      percentage of the participants, in the intervention and control groups, were in
      pre contemplation and contemplation stages in the pre-test (64 and 61,
      respectively). After the intervention, however, a significant improvement
      (p=0.001) was observed in the intervention group's stages of change compared to
      that in the control group. The distribution of the control group students
      regarding the stages of change was similar to that in the pre-test. CONCLUSION:
      The study findings revealed that the planned education programs are efficient to
      improve the adolescents' knowledge and behavioral intention in dealing with mass
      media messages.

PMID- 25587550
TI  - Academic training and clinical placement problems to achieve nursing competency.
AB  - INTRODUCTION: High quality of care is one of the requirements of nursing which
      depends on the nursing competency. In this connection, the aim of this research
      was to determine the problems related to the academic training (nursing'
      educational program) and clinical practice to achieve competency from the
      viewpoint of nurses, faculty members, and nursing students. METHODS: the study
      was an analytical cross-sectional one. The sample consisted of the academic
      staff, the third and the fourth year nursing students and nurses in practice. The
      instrument of the study was a two-part researcher-made questionnaire with 22
      questions in the theoretical- clinical realm to assess  problems related to the
      theoretical and clinical teaching in nursing, and 23 questions to assess the
      clinical functions. The questionnaire was validated in terms of both face and
      content validity. Its reliability, using Cronbach's Alpha coefficient, was 0.72
      in the theoretical-clinical and 0.73 in the clinical realm. Both descriptive and
      analytical statistics were used to analyze the data, using SPSS software.
      RESULTS: The results of this study indicated that from the participants'
      viewpoints, the most important problems in the academic education for nursea to
      acquire competency were as follows: lack of academic research the clinical period
      (88.9%), no application of theoretical aspects of the nursing process in practice
      (85.6%), insufficient knowledgeable and professional educators (81.1%), the use
      of traditional routine-oriented methods on the wards (75.6%); also insufficient
      time for performance based on knowledge in relation to  the nurse's workload
      (86.5%), weakness and usefulness of scientific function encouragement systems in
      clinic (85.2%), and learnt theoretical subjects not coming into practice in
      clinical fields after graduation (75.6%). CONCLUSION: Efforts to reduce the gap
      between the theoretical and practical (clinical function) knowledge in
      educational and work environment are required to improve the training of
      qualified nurses.

PMID- 25587551
TI  - Medical Students' and Physicians' Attitudes toward Patients' Consent to
      Participate in Clinical Training.
AB  - INTRODUCTION: The responsibility of the medical training team towards a patient
      referring to an academic medical center has not been fully clarified. In this
      article we have looked at current practice in Medical University of Isfahan and
      evaluated the attitude of the medical team towards patients'consent to be
      involved in medical students'education. METHODS: In this cross-sectional study,
      conducted in 2012, we distributed self-administrated questionnaires among medical
      mentors, residents and students of academic hospitals in Isfahan, Iran. This
      researcher-made questionnaire consisted of several questions concerning
      dimensions of informed consent. The data were analyzed, using independent t-tests
      and ANOVA. RESULTS: Ninety-one medical students (51 females) and 61 members of
      medical training team (25 females) completed the questionnaires. The overall
      average attitude score was 36.53+/-5.89 out of 60, which is classified as fair.
      The average attitude score for medical students and mentors were not
      significantly different. The average attitude score of the female students was
      classified as good, and was different from that of male students, significantly
      (p<0.05). By categorizing subjects into those with>=5 years of managerial or
      educational experience and those below 5, a significant difference in average
      attitude score was documented (35.8+/-2.54 in>=5and 34.0+/-2.9 in>5group).
      CONCLUSION: The attitude of the medical team is thoroughly far from what is
      expected. Thus, the need to provide both medical students and medical mentors
      with data on the importance of obtaining patients' consent to be involved in
      medical education is highlighted.

PMID- 25587552
TI  - Achievement motivation level in students of Shiraz University of Medical Sciences
      and its influential factors.
AB  - INTRODUCTION: Many studies have investigated the relationship between motivation
      and educational outcomes. The present study was conducted to determine whether
      the students' motivation in Shiraz University of Medical Sciences (SUMS)
      decreases during educational years. METHODS: 770 students in SUMS were selected
      by multi-stage stratified random sampling from each field and entrance year. The
      first questionnaire contained 57 questions on the effect of economic, social,
      educational, geographical and personality factors on the students' motivation.
      The second one was based on 50 incomplete sentences. The validity and reliability
      of these questionnaires were approved by the experts and Cronbach's Alpha
      coefficients (85% and 90%, respectively). In this cross-sectional study, ANOVA, t
      test and Chi-square tests were applied for data analysis at the 0.05 significance
      level. RESULTS: Six factors with the most effect on academic motivation were
      "family attitudes", "getting good jobs in future", "respect for themselves", "
      the ability to learn", "believing their role in victory and defeat" and "the
      tendency toward optimism about themselves". In addition, comparing professional
      doctorate and basic sciences' results revealed no significant relationship
      between academic motivation and educational years (F=0.819, p=0.397). But
      comparing field by field showed that Dentistry and Hospital Management and
      Medical Information (HMMI) had a significant decrease in motivation score by
      increase in educational years (F=3.991, p=0.015). CONCLUSION: Achievement
      motivation level in SUMS students was higher than average and did not decrease
      during educational years. Also, the results showed that personal, social and
      educational related factors affected motivation level more than economic and
      environmental factors.

PMID- 25587553
TI  - Medical ethics as practiced by students, nurses and faculty members in Shiraz
      University of Medical Sciences.
AB  - INTRODUCTION: Assuming any social role has obligations and fulfilling the related
      responsibilities has ethical aspects that must be addressed carefully. Each role
      requires extensive training, which usually takes place in university
      institutions. Ethics is applied in at least three academic areas, including: a)
      in education of students' personal growth, b) in patient care, and c) in
      university communion in population-based health care. Given the importance of
      this issue in the moral domain, this study examines the correlation among the
      students, nurses and teacher's opinions regarding principles of medical ethics at
      Shiraz University of Medical Sciences. METHODS: This is a descriptive-analytic
      and cross-sectional study conducted in 2010. The participants of this research
      consisted of all medical students, nurses in public hospitals, and faculty
      members in Shiraz University of Medical Sciences. For validity evaluation, the
      expert panel method and for reliability evaluation, test-retest method was used.
      RESULTS: Based on the medical ethics' scores in these three groups, there was a
      significant relationship between the mean scores of student-nurses and employed
      nurses, but there was no significant relationship between those of student
      faculties. Also the mean score of the students was the highest in medical ethics.
      CONCLUSION: In this study, we presented a list of virtues and moral
      characteristics of medical staff and found out the method of practicing medical
      ethics in everyday life of students to improve the moral reasoning of teachers,
      nurses and students. Moreover, medical ethics, with the presentation of specific
      criteria for ethical behavior in various domains of human life, especially in
      dealing with patients, can help practice ethical values in the medical community.

PMID- 25587554
TI  - Nursing students' perspectives on clinical education.
AB  - INTRODUCTION: The importance of optimal clinical nursing education in
      professional skills development is undeniable. In clinical education, nursing
      students are often faced with problems. Recognizing nursing students' perception
      on clinical education is the first step to remove the barriers of this challenge.
      Methods This descriptive cross-sectional study was conducted to determine the
      nursing students' perspectives on clinical education. 150 nursing students were
      selected randomly from nursing and midwifery schools (Tehran). Data collection
      instrument was a researcher made questionnaire consisting of five domains:
      objective and curricula, instructor, feedback to student in clinical field,
      clinical environment, supervision and evaluation. Mean and standard deviation
      were calculated for each item, using SPSS, ver.14. Chi- square test was used to
      compare the nursing students' perspectives on clinical education based on age,
      sex and the work experience. The significance level was considered 0.05. RESULTS:
      Mean age of the students was 21.58+/-26.97 students (66%) were male. 44 students
      (30.1%) had work experience (3.58+/-6.48 month). Male and female students had
      different perceptions in domains of clinical education (p<0.05). Nursing student
      had different perceptions as to objectives and curricula (p=0.039), how to deal
      with students in the clinical environment (p=0.032), supervision, and evaluation
      (p<0.001) with respect to their work experience duration. The most positive
      responses were in clinical instructor (81.5%) and the most negative ones were the
      clinical environment (33.66%), respectively. CONCLUSION: Providing an optimal
      clinical environment and improving the supervision and evaluation of student
      practice should prioritized in schools of nursing and midwifery.

PMID- 25587555
TI  - Clinical characteristics and outcomes of pediatric oncology patients with
      aggressive biology enrolled in phase I clinical trials designed for adults: the
      university of Texas MD anderson cancer center experience.
AB  - BACKGROUND: Children (patients <= 18 years of age) are not usually included on
      pharmaceutical industry sponsored Phase I trials. METHODS: We reviewed the
      medical records of 40 patients <= 18 years treated in >= 1 phase I trial at MD
      Anderson. RESULTS: The median OS was 8.5 months (95% CI, 5.5-13.2 months). In the
      multivariate analysis, age >=15 only predicted increased OS (P = 0.0065), and >3
      prior therapies (P = 0.053) predicted decreased OS. The median PFS was 2.8 months
      (95% CI, 2.3-4.1 months). In the multivariate analysis, independent factors that
      predicted increased PFS were age >=15 years (P < 0.001) and prior radiation
      therapy (P = 0.049); performance status >1 (P < 0.001) and >3 prior therapies (P
      = 0.002) predicted decreased PFS. RMH score >= 2 and MDACC score >= 3 were
      associated with decreased median OS (P = 0.029 and P = 0.031 respectively).
      CONCLUSIONS: It is feasible to conduct phase I studies in pediatric patients
      based on adult protocols. In the era of targeted therapy more trials should allow
      pediatric patients earlier in the drug development especially if deemed safe in
      adults in early phase trials. TRANSLATIONAL RELEVANCE: Most pharmaceutical
      industry sponsored trials exclude patients less than 18 years in phase I clinical
      trials. Even in the era of targeted therapy pediatric patients usually have to
      wait for most phases of trials to be completed in adults before being allowed to
      enroll in clinical trials of new therapies, even in the advanced metastatic and
      relapsed setting. Some investigator initiated phase 1 trials of combinations of
      US FDA approved agents allow patients less than 18 years. We report the
      preliminary analyses of the outcomes of pediatric patients enrolled in phase I
      studies initially designed for adults, but allowing for enrollment of patients
      under 18.

PMID- 25587556
TI  - Evolutionary behavioral genetics.
AB  - We describe the scientific enterprise at the intersection of evolutionary
      psychology and behavioral genetics-a field that could be termed Evolutionary
      Behavioral Genetics-and how modern genetic data is revolutionizing our ability to
      test questions in this field. We first explain how genetically informative data
      and designs can be used to investigate questions about the evolution of human
      behavior, and describe some of the findings arising from these approaches.
      Second, we explain how evolutionary theory can be applied to the investigation of
      behavioral genetic variation. We give examples of how new data and methods
      provide insight into the genetic architecture of behavioral variation and what
      this tells us about the evolutionary processes that acted on the underlying
      causal genetic variants.

PMID- 25587558
TI  - Dynamics of nonlinear systems.

PMID- 25587559
TI  - Induced neurocysticercosis in rhesus monkeys (Macaca mulatta) produces clinical
      signs and lesions similar to natural disease in man.
AB  - Neurocysticercosis is a serious endemic zoonosis resulting in increased cases of
      seizure and epilepsy in humans. The genesis of clinical manifestations of the
      disease through experimental animal models is poorly exploited. The monkeys may
      prove useful for the purpose due to their behavior and cognitive responses
      mimicking man. In this study, neurocysticercosis was induced in two rhesus
      monkeys each with 12,000 and 6,000 eggs, whereas three monkeys were given
      placebo. The monkeys given higher dose developed hyperexcitability, epileptic
      seizures, muscular tremors, digital cramps at 10 DPI, and finally paralysis of
      limbs, followed by death on 67 DPI, whereas the monkeys given lower dose showed
      delayed and milder clinical signs. On necropsy, all the infected monkeys showed
      numerous cysticerci in the brain. Histopathologically, heavily infected monkeys
      revealed liquefactive necrosis and formation of irregular cystic cavities lined
      by atrophied parenchymal septa with remnants of neuropil of the cerebrum. In
      contrast, the monkeys infected with lower dose showed formation of typical
      foreign body granulomas characterized by central liquefaction surrounded by
      chronic inflammatory response. It was concluded that the inflammatory and immune
      response exerted by the host against cysticerci, in turn, led to
      histopathological lesions and the resultant clinical signs thereof.

PMID- 25587557
TI  - Evaluation of the inhibition of carbohydrate hydrolyzing enzymes, the antioxidant
      activity, and the polyphenolic content of Citrus limetta peel extract.
AB  - Type 2 diabetes mellitus is one of the most frequent causes of death in Mexico,
      characterized by chronic hyperglycemia. One alternative strategy for this
      metabolic abnormality is inhibiting the enzymes responsible for the metabolism of
      carbohydrates. We evaluated whether the aqueous Citrus limetta peel extract could
      inhibit the metabolism of carbohydrates. We found that this extract inhibited
      primarily the enzyme alpha-amylase by 49.6% at a concentration of 20 mg/mL and to
      a lesser extent the enzyme alpha-glucosidase with an inhibition of 28.2% at the
      same concentration. This inhibition is likely due to the high polyphenol content
      in the Citrus limetta peel (19.1 mg GAE/g). Antioxidant activity of the Citrus
      limetta peel demonstrated dose-dependent antioxidant activity, varying from 6.5%
      at 1.125 mg/mL to 42.5% at 20 mg/mL. The study of these polyphenolic compounds
      having both antihyperglycemic and antioxidant activities may provide a new
      approach to the management of type 2 diabetes mellitus.

PMID- 25587560
TI  - Development of robust behaviour recognition for an at-home biomonitoring robot
      with assistance of subject localization and enhanced visual tracking.
AB  - Our research is focused on the development of an at-home health care
      biomonitoring mobile robot for the people in demand. Main task of the robot is to
      detect and track a designated subject while recognizing his/her activity for
      analysis and to provide warning in an emergency. In order to push forward the
      system towards its real application, in this study, we tested the robustness of
      the robot system with several major environment changes, control parameter
      changes, and subject variation. First, an improved color tracker was analyzed to
      find out the limitations and constraints of the robot visual tracking considering
      the suitable illumination values and tracking distance intervals. Then, regarding
      subject safety and continuous robot based subject tracking, various control
      parameters were tested on different layouts in a room. Finally, the main
      objective of the system is to find out walking activities for different patterns
      for further analysis. Therefore, we proposed a fast, simple, and person specific
      new activity recognition model by making full use of localization information,
      which is robust to partial occlusion. The proposed activity recognition algorithm
      was tested on different walking patterns with different subjects, and the results
      showed high recognition accuracy.

PMID- 25587561
TI  - Histological features of the gastrointestinal tract of wild Indonesian shortfin
      eel, Anguilla bicolor bicolor (McClelland, 1844), captured in Peninsular
      Malaysia.
AB  - This study was conducted to record the histological features of the
      gastrointestinal tract of wild Indonesian shortfin eel, Anguilla bicolor bicolor
      (McClelland, 1844), captured in Peninsular Malaysia. The gastrointestinal tract
      was segmented into the oesophagus, stomach, and intestine. Then, the oesophagus
      was divided into five (first to fifth), the stomach into two (cardiac and
      pyloric), and the intestine into four segments (anterior, intermediate,
      posterior, and rectum) for histological examinations. The stomach had
      significantly taller villi and thicker inner circular muscles compared to the
      intestine and oesophagus. The lamina propria was thickest in stomach,
      significantly when compared with oesophagus, but not with the intestine. However,
      the intestine showed significantly thicker outer longitudinal muscle while
      gastric glands were observed only in the stomach. The histological features were
      closely associated with the functions of the different segments of the
      gastrointestinal tract. In conclusion, the histological features of the
      gastrointestinal tract of A. b. bicolor are consistent with the feeding habit of
      a carnivorous fish.

PMID- 25587562
TI  - Recent advances in communications and networking.

PMID- 25587563
TI  - The filtering of the posturographic signals shows the age related features.
AB  - OBJECTIVE: Lower frequencies of slow oscillations of the posturographic signals
      can be removed using high-pass filtering. This procedure releases postural
      reflexes possessing higher frequencies and lower amplitude range. Mutual
      dependence between the x and y components of posturographic signals was analyzed
      using principal component analysis (PCA). The posturographic signals of old
      patients with idiopathic gait disturbance were compared with the control group of
      similar age and with younger patients. There was also the analysis of the
      influence of the eyes state (open versus closed) and the head position (normal or
      bent back). The statistically significant differences in the mutual dependence
      between x and y components between the groups of patients were analyzed using
      MANOVA. The significant differences were observed mainly in the range of filter
      frequencies f = 0.1-1.5 Hz and f = 2.2-5.5 Hz with a maximum effect at
      approximately 4-5 Hz. A detailed post-hoc analysis is also presented. The
      differences in the higher frequency range suggest the main disturbance to be
      connected with the spinal reflexes. Visual and vestibular support appear
      insufficient for postural stability control in the idiopathic gait disturbance
      group. The results suggest that idiopathic gait disturbance is the final stage of
      the aging process of postural system.

PMID- 25587564
TI  - Seropositivity of dengue antibodies during pregnancy.
AB  - PURPOSE: Malaysia a dengue endemic country with dengue infections in pregnancy on
      the rise. The present study was aimed at determining dengue seroprevalence (IgG
      or IgM) during pregnancy and its neonatal transmission in dengue seropositive
      women. METHODS: Maternal with paired cord blood samples were tested for dengue
      antibodies (IgG and IgM) using an enzyme-linked immunosorbent assay (ELISA).
      Maternal age, parity, occupation, ethnic group, and gestational age were
      recorded. Data on neonatal Apgar score and admissions to the Neonatal Intensive
      Care Unit (NICU) were analyzed. RESULTS: Out of 358 women recruited, about 128
      (35.8%) patients were seropositive. Twelve patients (3.4%) had recent infections
      (IgM positive) and another 116 women (32.4%) were with past infections (IgG
      positive). All babies born to seropositive mothers had positive IgG paired cord
      blood; however, no IgM seropositivity was observed. All neonates had good Apgar
      scores and did not require NICU admission. CONCLUSION: In this study, 35.8%
      pregnant women were found to be dengue seropositive. However, transplacental
      transfer of IgG antibodies had no detrimental effect on the neonatal outcomes.

PMID- 25587565
TI  - Characterization of antibiotic producing rare actinomycete Nonomuraea sp. JAJ18
      derived from an Indian coastal solar saltern.
AB  - Rare actinomycete genera are accepted as a promising source of novel metabolites
      having pharmaceutical importance. One such genus of rare actinomycete is
      Nonomuraea. The present study was aimed at characterizing the antibiotic
      producing Nonomuraea strain JAJ18 which was previously isolated from coastal
      solar saltern. Strain JAJ18 was recognized as a member of genus Nonomuraea based
      on its almost complete 16S rRNA gene sequence and phenotypic characteristics. The
      strain JAJ18 was found to be closely related to Nonomuraea maheshkhaliensis 16-5
      14(T) (98.90%), Nonomuraea candida HMC10(T) (98.58%), and Nonomuraea jabiensis
      A4036(T) (98.43%). From cell-free culture broth of strain JAJ18, an antibiotic
      was extracted and purified by silica column chromatography. The obtained
      antibiotic was found to be active against a range of Gram-positive and Gram
      negative bacteria including drug-resistant Staphylococcus, with minimal
      inhibitory concentration (MIC) ranging from 0.5 to 16.0 ug mL(-1). The structural
      characteristics of antibiotic were determined by FTIR and NMR spectroscopy. The
      antibiotic was identified to be an aliphatic rich compound with significant
      dissimilarity to known antibiotics reported from members of the genus,
      Nonomuraea. As the trends to discover novel metabolites from Nonomuraea are
      vibrant, further studies are needed to understand the structural and
      biotechnological significance of antibiotic compound produced by Nonomuraea sp.
      JAJ18.

PMID- 25587566
TI  - Biomechanics of gait during pregnancy.
AB  - INTRODUCTION: During pregnancy women experience several changes in the body's
      physiology, morphology, and hormonal system. These changes may affect the balance
      and body stability and can cause discomfort and pain. The adaptations of the
      musculoskeletal system due to morphological changes during pregnancy are not
      fully understood. Few studies clarify the biomechanical changes of gait that
      occur during pregnancy and in postpartum period. PURPOSES: The purpose of this
      review was to analyze the available evidence on the biomechanical adaptations of
      gait that occur throughout pregnancy and in postpartum period, specifically with
      regard to the temporal, spatial, kinematic, and kinetic parameters of gait.
      METHODS: Three databases were searched and 9 studies with a follow-up design were
      retrieved for analysis. RESULTS: Most studies performed temporal, spatial, and
      kinematic analysis. Only three studies performed kinetic analysis. CONCLUSION.
      The adaptation strategies to the anatomical and physiological changes throughout
      pregnancy are still unclear, particularly in a longitudinal perspective and
      regarding kinetic parameters.

PMID- 25587568
TI  - Transcriptome sequencing in a Tibetan barley landrace with high resistance to
      powdery mildew.
AB  - Hulless barley is an important cereal crop worldwide, especially in Tibet of
      China. However, this crop is usually susceptible to powdery mildew caused by
      Blumeria graminis f. sp. hordei. In this study, we aimed to understand the
      functions and pathways of genes involved in the disease resistance by
      transcriptome sequencing of a Tibetan barley landrace with high resistance to
      powdery mildew. A total of 831 significant differentially expressed genes were
      found in the infected seedlings, covering 19 functions. Either "cell," "cell
      part," and "extracellular region" in the cellular component category or "binding"
      and "catalytic" in the category of molecular function as well as "metabolic
      process" and "cellular process" in the biological process category together
      demonstrated that these functions may be involved in the resistance to powdery
      mildew of the hulless barley. In addition, 330 KEGG pathways were found using
      BLASTx with an E-value cut-off of <10(-5). Among them, three pathways, namely,
      "photosynthesis," "plant-pathogen interaction," and "photosynthesis-antenna
      proteins" had significant matches in the database. Significant expressions of the
      three pathways were detected at 24 h, 48 h, and 96 h after infection,
      respectively. These results indicated a complex process of barley response to
      powdery mildew infection.

PMID- 25587570
TI  - Video multiple watermarking technique based on image interlacing using DWT.
AB  - Digital watermarking is one of the important techniques to secure digital media
      files in the domains of data authentication and copyright protection. In the
      nonblind watermarking systems, the need of the original host file in the
      watermark recovery operation makes an overhead over the system resources, doubles
      memory capacity, and doubles communications bandwidth. In this paper, a robust
      video multiple watermarking technique is proposed to solve this problem. This
      technique is based on image interlacing. In this technique, three-level discrete
      wavelet transform (DWT) is used as a watermark embedding/extracting domain,
      Arnold transform is used as a watermark encryption/decryption method, and
      different types of media (gray image, color image, and video) are used as
      watermarks. The robustness of this technique is tested by applying different
      types of attacks such as: geometric, noising, format-compression, and image
      processing attacks. The simulation results show the effectiveness and good
      performance of the proposed technique in saving system resources, memory
      capacity, and communications bandwidth.

PMID- 25587567
TI  - Role of melatonin in traumatic brain injury and spinal cord injury.
AB  - Brain and spinal cord are implicated in incidences of two of the most severe
      injuries of central nervous system (CNS). Traumatic brain injury (TBI) is a
      devastating neurological deficit involving primary and secondary injury cascades.
      The primary and secondary mechanisms include complex consequences of activation
      of proinflammatory cytokines, cerebral edema, upregulation of NF-kappa beta,
      disruption of blood-brain barrier (BBB), and oxidative stress. Spinal cord injury
      (SCI) includes primary and secondary injury cascades. Primary injury leads to
      secondary injury in which generation of free radicals and oxidative or nitrative
      damage play an important pathophysiological role. The indoleamine melatonin is a
      hormone secreted or synthesized by pineal gland in the brain which helps to
      regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone
      having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory
      properties. It has a special characteristic of crossing BBB. Melatonin has
      neuroprotective role in the injured part of the CNS after TBI and SCI. A number
      of studies have successfully shown its therapeutic value as a neuroprotective
      agent in the treatment of neurodegenerative diseases. Here in this review we have
      compiled the literature supporting consequences of CNS injuries, TBI and SCI, and
      the protective role of melatonin in it.

PMID- 25587571
TI  - Recent advances on internet of things.

PMID- 25587569
TI  - Outer membrane proteome analysis of Indian strain of Pasteurella multocida
      serotype B:2 by MALDI-TOF/MS analysis.
AB  - Identification of outer membrane proteins (OMPs) is important to understand the
      bacteria structure and function, host-pathogen interaction, development of novel
      vaccine candidates, and diagnostic antigens. But till now the key antigens of P.
      multocida B:2 isolate causing haemorrhagic septicaemia (HS) in animals are not
      clearly defined. In this study, P52 strain of P. multocida serotype B:2 was grown
      in vitro under iron-rich and iron-limited condition. The OMPs were extracted by
      sarkosyl method followed by SDS-PAGE and the proteins were identified by MALDI
      TOF/MS analysis. In total, 22 proteins were identified, of which 7 were observed
      exclusively under iron-limited condition. Most of the high molecular weight
      proteins (TbpA, HgbA, HgbB, HasR, IroA, and HemR) identified in this study were
      involved in iron acquisition. Some hypothetical proteins (HP-KCU-10206, HP and
      AAUPMB 08244, HP AAUPMB 21592, HP AAUPMB 19766, AAUPMB 11295) were observed for
      the first time in this study which could be unique to serotype B:2. Further
      functional in vivo study of the proteins identified are required to explore the
      utility of these proteins in developing diagnostics and vaccine against HS.

PMID- 25587573
TI  - The moss flora of Akdag Mountain (Amasya, Turkey).
AB  - The moss flora of Akdag Mountain (Amasya, Turkey) was investigated. At the result
      of identifications of 1500 moss specimens, collected from the research area, 178
      taxa belonging to 69 genera and 26 families were determined. Among them, 94 taxa
      are new for A3 grid square according to the Turkey grid system which was adopted
      by Henderson. The location data of Grimmia crinitoleucophaea Cardot and Barbula
      enderesii Garov. are the first records for Turkey, and Encalypta spathulata Mull.
      Hal., Schistidium dupretii (Ther.) W. A. Weber, Weissia condensa var. armata
      (Ther. & Trab.) M. J. Cano, Ros & J. Guerra, Tortella bambergeri (Schimp.),
      Barbula enderesii Garov., Hedwigia ciliata var. leucophaea Bruch & Schimp., and
      Campyliadelphus elodes (Lindb.) Kanda are recorded for the second time to the
      byroflora of Turkey.

PMID- 25587572
TI  - The meaning of collaboration, from the perspective of Iranian nurses: a
      qualitative study.
AB  - BACKGROUND: Interdisciplinary collaboration among nurses is a complex and
      multifaceted process, an essential element in nursing, which is crucial to
      maintain an efficient, safe, and viable medical setting. The aim of this study
      was to explore the meaning of concept of collaboration through conducting a
      qualitative research approach. METHOD: The present study is qualitatively
      conducted in a content analysis approach. The data collection process included 18
      unstructured and in-depth interviews with nurses during 2012-2013 in educational
      medical centers of west and northwest of Iran. A purposive sampling method was
      used. All the interviews were recorded, transcribed, and finally analyzed using a
      qualitative content analysis with a conventional method. RESULT: Categories
      obtained from analysis of the data to explain the meaning of collaboration
      consist of (i) prerequisites of collaboration, (ii) actualization of
      collaboration, and (iii) achievement of a common goal. CONCLUSION: The results of
      the present study ended in the discovery of meaning of collaboration that confirm
      results of other related studies, hence clarifying and disambiguating the concept
      under study. These results also contribute to the development of collaboration
      theories and the relevant measurement tools.

PMID- 25587574
TI  - Cell hydration as a biomarker for estimation of biological effects of nonionizing
      radiation on cells and organisms.
AB  - "Changes in cell hydration" have been hypothesized as an input signal for
      intracellular metabolic cascade responsible for biological effects of nonionizing
      radiation (NIR). To test this hypothesis a comparative study on the impacts of
      different temperature and NIR (infrasound frequency mechanical vibration (MV),
      static magnetic field (SMF), extremely low frequency electromagnetic field (ELF
      EMF), and microwave (MW)) pretreated water on the hydration of barley seeds in
      its dormant and germination periods was performed. In dormant state temperature
      sensitivity (Q 10) of seed hydration in distilled water (DW) was less than 2, and
      it was nonsensitive to NIR treated DW, whereas during the germination period (48
      72 hours) seeds hydration exhibited temperature sensitivity Q 10 > 2 and higher
      sensitivity to NIR treated DW. Obtained data allow us to suggest that the
      metabolic driving of intracellular water dynamics accompanied by hydrogen bonding
      and breaking is more sensitive to NIR-induced water structure changes in seed
      bathing aqua medium than the simple thermodynamic processes such as osmotic
      gradient driven water absorption by seeds in dormant state. Therefore, cell
      hydration is suggested to be a universal and extrasensitive biomarker for
      detection of biological effects of NIR on cells and organisms.

PMID- 25587575
TI  - Inheritance of nitrogen use efficiency in inbred progenies of tropical maize
      based on multivariate diallel analysis.
AB  - The objective of our study was to characterize and determine the patterns of
      genetic control in relation to tolerance and efficiency of nitrogen use by means
      of a complete diallel cross involving contrasting inbred progenies of tropical
      maize based on a univariate approach within the perspective of a multivariate
      mixed model. Eleven progenies, previously classified regarding the tolerance and
      responsiveness to nitrogen, were crossed in a complete diallel cross. Fifty-five
      hybrids were obtained. The hybrids and the progenies were evaluated at two
      different nitrogen levels, in two locations. The grain yield was measured as well
      as its yield components. The heritability values between the higher and lower
      nitrogen input environment did not differ among themselves. It was observed that
      the general combining ability values were similar for both approaches univariate
      and multivariate, when it was analyzed within each location and nitrogen level.
      The estimate of variance of the specific combining ability was higher than
      general combining ability estimate and the ratio between them was 0.54. The
      univariate and multivariate approaches are equivalent in experiments with good
      precision and high heritability. The nonadditive genetic effects exhibit greater
      quantities than the additive genetic effects for the genetic control of nitrogen
      use efficiency.

PMID- 25587577
TI  - Characterization of core-shell MOF particles by depth profiling experiments using
      on-line single particle mass spectrometry.
AB  - Materials with core-shell structures have distinct properties that lend
      themselves to a variety of potential applications. Characterization of small
      particle core-shell materials presents a unique analytical challenge. Herein,
      single particles of solid-state materials with core-shell structures were
      measured using on-line aerosol time-of-flight mass spectrometry (ATOFMS). Laser
      'depth profiling' experiments verified the core-shell nature of two known core
      shell particle configurations (<2 MUm diameter) that possessed inverted,
      complimentary core-shell compositions (ZrO2@SiO2 versus SiO2@ZrO2). The average
      peak area ratios of Si and Zr ions were calculated to definitively show their
      core-shell composition. These ratio curves acted as a calibrant for an
      uncharacterized sample - a metal-organic framework (MOF) material surround by
      silica (UiO-66(Zr)@SiO2; UiO = University of Oslo). ATOFMS depth profiling was
      used to show that these particles did indeed exhibit a core-shell architecture.
      The results presented here show that ATOFMS can provide unique insights into core
      shell solid-state materials with particle diameters between 0.2-3 MUm.

PMID- 25587576
TI  - Prescribing multiple neurostimulants during rehabilitation for severe brain
      injury.
AB  - BACKGROUND: Despite a lack of clear evidence, multiple neurostimulants are
      commonly provided after severe brain injury (BI). The purpose of this study is to
      determine if the number of neurostimulants received during rehabilitation was
      associated with recovery of full consciousness or improved neurobehavioral
      function after severe BI. METHOD: Data from 115 participants were extracted from
      a neurobehavioral observational study database for this exploratory,
      retrospective analysis. Univariate optimal data analysis was conducted to
      determine if the number of neurostimulants influenced classification of four
      outcomes: recovery of full consciousness during rehabilitation, recovery of full
      consciousness within one year of injury, and meaningful neurobehavioral
      improvement during rehabilitation defined as either at least a 4.7 unit (minimal
      detectable change) or 2.58 unit (minimal clinically important difference) gain on
      the Disorders of Consciousness Scale-25 (DOCS-25). RESULTS: Number of
      neurostimulants was not significantly (P > 0.05) associated with recovery of full
      consciousness during rehabilitation, within one year of injury, or meaningful
      neurobehavioral improvement using the DOCS-25. CONCLUSIONS: Receiving multiple
      neurostimulants during rehabilitation may not influence recovery of full
      consciousness or meaningful neurobehavioral improvement. Given costs associated
      with additional medication, future research is needed to guide physicians about
      the merits of prescribing multiple neurostimulants during rehabilitation after
      severe BI.

PMID- 25587580
TI  - On Asylums: Essays on the social stituation of mental patients and other inmates,
      by Irving Goffmann.

PMID- 25587579
TI  - Assessing dimerisation degree and cooperativity in a biomimetic small-molecule
      model by pulsed EPR.
AB  - Pulsed electron paramagnetic resonance (EPR) spectroscopy is gaining increasing
      importance as a complementary biophysical technique in structural biology. Here,
      we describe the synthesis, optimisation, and EPR titration studies of a spin
      labelled terpyridine Zn(II) complex serving as a small-molecule model system for
      tuneable dimerisation.

PMID- 25587581
TI  - In a coma.

PMID- 25587582
TI  - New hopes for gene therapy.

PMID- 25587583
TI  - Bernard Wood.

PMID- 25587584
TI  - In memoriam: Dietrich Lehmann, 1929-2014.

PMID- 25587585
TI  - Will the Nicaragua Canal connect or divide?
AB  - A century after the opening of the Panama Canal, a second inter-oceanic passage
      is set to be built in Central America, this time in Nicaragua. The ambitious and
      astronomically expensive project promises to bring economic opportunity to a poor
      country but it also carries risks to its tropical ecosystems. Will the new
      waterway ultimately link two oceans or divide a continent? Michael Gross
      investigates.

PMID- 25587586
TI  - Ronald R. Hoy.

PMID- 25587587
TI  - Standardization of terminology in stereotactic radiosurgery: Report from the
      Standardization Committee of the International Leksell Gamma Knife Society:
      special topic.
AB  - OBJECT: This report has been prepared to ensure more uniform reporting of Gamma
      Knife radiosurgery treatment parameters by identifying areas of controversy,
      confusion, or imprecision in terminology and recommending standards. METHODS:
      Several working group discussions supplemented by clarification via email allowed
      the elaboration of a series of provisional recommendations. These were also
      discussed in open session at the 16th International Leksell Gamma Knife Society
      Meeting in Sydney, Australia, in March 2012 and approved subject to certain
      revisions and the performance of an Internet vote for approval from the whole
      Society. This ballot was undertaken in September 2012. RESULTS: The
      recommendations in relation to volumes are that Gross Target Volume (GTV) should
      replace Target Volume (TV); Prescription Isodose Volume (PIV) should generally be
      used; the term Treated Target Volume (TTV) should replace TVPIV, GTV in PIV, and
      so forth; and the Volume of Accepted Tolerance Dose (VATD) should be used in
      place of irradiated volume. For dose prescription and measurement, the
      prescription dose should be supplemented by the Absorbed Dose, or DV% (for
      example, D95%), the maximum and minimum dose should be related to a specific
      tissue volume (for example, D2% or preferably D1 mm3), and the median dose (D50%)
      should be recorded routinely. The Integral Dose becomes the Total Absorbed Energy
      (TAE). In the assessment of planning quality, the use of the Target Coverage
      Ratio (TTV/ GTV), Paddick Conformity Index (PCI = TTV2/[GTV . PIV]), New
      Conformity Index (NCI = [GTV . PIV]/TTV2), Selectivity Index (TTV/PIV),
      Homogeneity Index (HI = [D2% -D98%]/D50%), and Gradient Index (GI = PIV0.5/PIV)
      are reemphasized. In relation to the dose to Organs at Risk (OARs), the emphasis
      is on dose volume recording of the VATD or the dose/volume limit (for example,
      V10) in most cases, with the additional use of a Maximum Dose to a small volume
      (such as 1 mm3) and/or a Point Dose and Mean Point Dose in certain circumstances,
      particularly when referring to serial organs. The recommendations were accepted
      by the International Leksell Gamma Knife Society by a vote of 92% to 8%.
      CONCLUSIONS: An agreed-upon and uniform terminology and subsequent
      standardization of certain methods and procedures will advance the clinical
      science of stereotactic radiosurgery.

PMID- 25587589
TI  - The Anatomische Gesellschaft mourns an honorary fellow, Joachim-Hermann Scharf.

PMID- 25587588
TI  - Design, synthesis and biological evaluation of metronidazole-thiazole derivatives
      as antibacterial inhibitors.
AB  - A series of metronidazole-thiazole derivatives has been designed, synthesized and
      evaluated as potential antibacterial inhibitors. All the synthesized compounds
      were determined by elemental analysis, (1)H NMR and MS. They were also tested for
      antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus
      subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The
      results showed that compound 5 e exhibited the most potent inhibitory activity
      against E. coli FabH with IC50 of 4.9 lM. Molecular modeling simulation studies
      were performed in order to predict the biological activity of proposed compounds.
      Toxicity assay of compounds 5 a, 5 b, 5 d, 5 e, 5 g and 5 i showed that they were
      noncytotoxic against human macrophage. The results revealed that these compounds
      offered remarkable viability.

PMID- 25587590
TI  - Introduction: atherosclerosis.

PMID- 25587591
TI  - Words of wisdom. Re: Radical prostatectomy or watchful waiting in early prostate
      cancer.

PMID- 25587592
TI  - Words of wisdom. Re: Screening and prostate cancer mortality: results of the
      European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of
      follow-up.

PMID- 25587593
TI  - Words of wisdom. Re: Coadministration of anastrozole sustains therapeutic
      testosterone levels in hypogonadal men undergoing testosterone pellet insertion.

PMID- 25587594
TI  - Words of wisdom. Re: Rapid induction of androgen receptor splice variants by
      androgen deprivation in prostate cancer.

PMID- 25587595
TI  - Words of wisdom. Re: Antibody-drug conjugates targeting prostate-specific
      membrane antigen.

PMID- 25587596
TI  - Retraction notice to: 'Reply from authors re: Declan G. Murphy, Anthony J.
      Costello. How can the autonomic nervous system contribute to urinary continence
      following radical prostatectomy? A ''Boson-like'' conundrum. Eur urol 2013;63:445
      7: Sparing of the neurovascular bundle leads to improved rates of continence'
      [Eur urol 2013;63:447-9].

PMID- 25587597
TI  - With this issue of Transfusion and Apheresis Science, we  mark the passing, last
      year, of one of the most important  early figures in apheresis. Introduction.

PMID- 25587598
TI  - Measurement characteristics and clinical utility of the high-level mobility
      assessment tool among individuals with traumatic brain injury.

PMID- 25587599
TI  - Words of wisdom. Re: Vasectomy and risk of aggressive prostate cancer: a 24-year
      follow-up study.

PMID- 25587611
TI  - A 66-year-old patient with progressive left hemiparesis: question.

PMID- 25587612
TI  - An unusual cause of chronic headaches: question.

PMID- 25587613
TI  - Cystic fibrosis: An update for clinicians. Part 1: Nutrition  and
      gastrointestinal complications.

PMID- 25587614
TI  - Decreased density of CD3+ tumor-infiltrating lymphocytes during gastric cancer
      progression.

PMID- 25587615
TI  - Autofluorescence imaging endoscopy for predicting acid  reflux in patients with
      gastroesophageal reflux disease.

PMID- 25587616
TI  - Interleukin-28B rs12979860 C allele: Protective against  advanced fibrosis in
      chronic hepatitis C genotype  1 infection.
AB  - Background and Aim: While genetic polymorphisms upstream of the interleukin
      28B(IL28B) gene are associated with necroinflammatory activity grade in chronic
      hepatitis C virus genotype 1 (HCV-1) infection, any association with fibrosis is
      less definitive. Pretreatment liver biopsies in a cohort of treatment-naive
      patients with HCV-1 were analyzed to evaluate associations between liver
      histology, and the rs12979860 and rs8099917 IL28B single nucleotide
      polymorphisms.Methods: Two hundred sixty-six patients with HCV-1 infection and
      pretreatment liver biopsy were tested for the rs12979860 and rs8099917 single
      nucleotide polymorphisms.Predictors of advanced fibrosis (METAVIR F3/4) and high
      activity grade (A2/3) were identified using multivariable logistic regression
      analysis.Results: Forty-four patients (16.5%) had advanced fibrosis and 141
      patients (53.0%) high activity grade. Prevalence of rs12979860 IL28B genotype
      was: CC 45.7%, CT 42.7%, and TT 11.6%. Prevalence of advanced fibrosis was lower
      in those with IL28B CC genotype compared with those without (11.0% vs 21.3%; P =
      0.03), with an increasing number of Talleles associated with a higher frequency
      of advanced fibrosis: CC 11.0%, CT 18.0%, TT33.3% (P = 0.01). Predictors of
      advanced fibrosis on multivariate analysis were platelet count (odds ratio [OR]
      0.98, 95% confidence interval [CI] 0.97-0.99; P < 0.0001), high activity grade
      (OR 5.68, 95% CI% 1.86-17.32; P = 0.002), IL28B rs12979860 CC genotype(OR 0.36,
      95% CI 0.14-0.93; P = 0.03), and aspartate aminotransferase (OR 1.02,95% CI 1.00
      1.03; P = 0.046). No association was found between rs8099917 IL28B genotype and
      liver histology.Conclusions: IL28B rs12979860 CC genotype appears to be
      independently associated with a lower prevalence of advanced fibrosis stage in
      HCV-1 infection. This association warrants further evaluation.

PMID- 25587617
TI  - Entecavir plus adefovir versus adefovir plus lamivudine in  hepatitis B virus e
      antigen-positive, lamivudine-resistant  chronic hepatitis B.

PMID- 25587618
TI  - Clinicopathologic analysis of the simple nodular type of  well-differentiated
      hepatocellular carcinoma with extensive  peliotic change.

PMID- 25587620
TI  - Regulation of T cell recruitment and inflammation in the  human immunodeficiency
      virus/hepatitis C virus  coinfected liver.

PMID- 25587619
TI  - Markers of endothelial dysfunction in patients with  non-alcoholic fatty liver
      disease and coronary artery disease.

PMID- 25587621
TI  - Colorado ASC reaches out to community with annual free surgery day.

PMID- 25587622
TI  - You can't say that: using social media in the healthcare setting requires sound
      judgment.

PMID- 25587623
TI  - Sharpen coding skills and reimbursement strategies during ICD-10 delay.

PMID- 25587624
TI  - Vibrational signatures of cation-anion hydrogen bonding in ionic liquids: a
      periodic density functional theory and molecular dynamics study.
AB  - Hydrogen bonding in alkylammonium based protic ionic liquids was studied using
      density functional theory (DFT) and ab initio molecular dynamics (AIMD)
      simulations. Normal-mode analysis within the harmonic approximation and power
      spectra of velocity autocorrelation functions were used as tools to obtain the
      vibrational spectra in both the gas phase and the crystalline phases of these
      protic ionic liquids. The hydrogen bond vibrational modes were identified in the
      150-240 cm(-1) region of the far-infrared (far-IR) spectra. A blue shift in the
      far-IR mode was observed with an increasing number of hydrogen-bonding sites on
      the cation; the exact peak position is modulated by the cation-anion hydrogen
      bond strength. Sub-100 cm(-1) bands in the far-IR spectrum are assigned to the
      rattling motion of the anions. Calculated NMR chemical shifts of the acidic
      protons in the crystalline phase of these salts also exhibit the signature of
      cation-anion hydrogen bonding. 

PMID- 25587625
TI  - NADH->NAD+ Transhydrogenation in Adult Ascaris suum Mitochondria.
AB  - Although lacking an NADPH->NAD(+) transhydrogenase system, the essentially
      energetically anaerobic mitochondria of the adult intestinal nematode Ascaris
      suum display an inner membrane-associated NADH->NAD(+) transhydrogenation
      reaction. This reaction is considered to be reflective of a mechanism(s) that
      acts in catalyzing a transmembrane translocation of reducing equivalents from
      NADH in the intermembrane space to matrix NAD(+), thereby forming matrix NADH
      that would serve in electron transport. Ascarid mitochondrial lipoamide
      dehydrogenase rather than an NADH->NAD(+) transhydrogenase system has been viewed
      as the predominant source of inner membrane-associated NADH->NAD(+)
      transhydrogenation activity. However, the present study made apparent yet another
      source of mitochondrial, inner membrane-associated NADH->NAD(+) activity in A.
      suum , viz., NADH dehydrogenase. This was made evident via comparisons of the A.
      suum mitochondrial NADH->NAD(+) transhydrogenation, NADH dehydrogenase, and
      lipoamide dehydrogenase activities in terms of pH effects, thermal labilities,
      the involvement of NADH dehydrogenase in the activities of mitochondrial,
      membrane-associated rotenone-insensitive and rotenone-sensitive NADH-dependent
      cytochrome c reductases, and mitochondrial membrane versus mitochondrial soluble
      localizations. Studies of the responses of the NADH->NAD(+) transhydrogenation,
      rotenone-insensitive and rotenone-sensitive cytochrome c reductases, and
      lipoamide dehydrogenase activities to inhibition by copper and cadmium lent
      additional support to the catalysis of an NADH->NAD(+) transhydrogenation
      activity by NADH dehydrogenase. Collectively, the data presented are consistent
      with an additional physiological catalysis of an NADH->NAD(+) transhydrogenation
      in A. suum mitochondria by an inner membrane NADH dehydrogenase component of the
      rotenone-sensitive cytochrome c reductase system, i.e., the NADH dehydrogenase
      component of the electron transport system. Comparisons of the A. suum data with
      those from other essentially anaerobic helminth parasites as well as free-living
      eukaryotic mitochondrial systems are noted. 

PMID- 25587626
TI  - Tuning mechanical properties of pharmaceutical crystals with multicomponent
      crystals: voriconazole as a case study.
AB  - Crystals of voriconazole, an antifungal drug, are soft in nature, and this is
      disadvantageous during compaction studies where pressure is applied on the solid.
      Crystal engineering is used to make cocrystals and salts with modified mechanical
      properties (e.g., hardness). Cocrystals with biologically safe coformers such as
      fumaric acid, 4-hydroxybenzoic acid, and 4-aminobenzoic acid and salts with
      hydrochloric acid and oxalic acid are prepared through solvent assisted grinding.
      The presence (salt) or absence (cocrystal) of proton transfer in these
      multicomponent crystals is unambiguously confirmed with single crystal X-ray
      diffraction. All the cocrystals have 1:1 stoichiometry, whereas salts exhibit
      variable stoichiometries such as HCl salt (1:2) and oxalate salts (1:1.5 and
      1:1). The nanoindentation technique was applied on single crystals of the salts
      and cocrystals. The salts exhibit better hardness than the drug and cocrystals in
      the order salts ? drug > cocrystals. The molecular origin of this mechanical
      modulation is explained on the basis of slip planes in the crystal structure and
      relative orientations of the molecules with respect to the nanoindentation
      direction. The hydrochloride salt is the hardest solid in this family. This may
      be useful for tableting of the drug during formulation and in drug development. 

PMID- 25587627
TI  - Heat shock, visible light or high calcium augment the cytotoxic effects of
      Ailanthus altissima (Swingle) leaf extracts against Saccharomyces cerevisiae
      cells.
AB  - To gain new insight into the antimicrobial potential of Ailanthus altissima
      Swingle, ethanol leaf extracts were evaluated for the antifungal effects against
      the model yeast Saccharomyces cerevisae. The extracts inhibited the yeast growth
      in a dose-dependent manner, and this effect could be augmented by heat shock,
      exposure to visible light or exposure to high concentrations of Ca(2+). Using
      transgenic yeast cells expressing the Ca(2+)-dependent photoprotein, aequorin, it
      was found that the leaf extracts induced cytosolic Ca(2+) elevation. Experiments
      on yeast mutants with defects in Ca(2+) transport demonstrated that the
      cytotoxicity of the A. altissima leaf extracts (AaLEs) was mediated by transient
      pulses of Ca(2+) ions which were released into the cytosol predominantly from the
      vacuole. The investigation of the antifungal synergies involving AaLEs may
      contribute to the development of optimal and safe combination therapies for the
      treatment of drug-resistant fungal infections. 

PMID- 25587628
TI  - Improvement of urban lake water quality by removal of Escherichia coli through
      the action of the bivalve Anodonta californiensis.
AB  - High levels of fecal indicator bacteria, such as Escherichia coli, can be
      indicative of poor water quality. The use of shellfish to reduce eutrophication
      has been proposed, but application of bivalves to reduce bacterial levels has not
      been extensively reported. Removal of E. coli by the native freshwater mussel
      Anodonta californiensis was studied using laboratory batch systems and field
      based flow-through systems. Batch systems were utilized to determine the fate and
      inactivation of E. coli after uptake by the mussel. Batch experiments
      demonstrated that uptake patterns followed first order kinetics and E. coli was
      inactivated with less than 5% of the initial colonies recoverable in fecal matter
      or tissue. Flow-through systems located at an urban impaired lake in San
      Francisco, CA were utilized to determine uptake kinetics under environmentally
      relevant conditions. The bivalves maintained a 1-log removal of E. coli for the
      duration of exposure. The calculated uptake rates can be used in conjunction with
      hydrologic models to determine the number of bivalves needed to maintain removal
      of E. coli in different freshwater systems. The outcomes of this study support
      the use of native freshwater bivalves to achieve the co-benefits of
      rehabilitating a freshwater ecosystem and improving water quality via reduction
      of E. coli in contaminated freshwater systems. 

PMID- 25587630
TI  - Combustion chemistry via metadynamics: benzyl decomposition revisited.
AB  - Large polycyclic aromatic hydrocarbons (PAHs) are thought to be responsible for
      the formation of soot particles in combustion processes. However, there are still
      uncertainties on the course that leads small molecules to form PAHs. This is
      largely due to the high number of reactions and intermediates involved.
      Metadynamics combined with ab initio molecular dynamics can provide a very
      precious contribution because offers the possibility to explore new possible
      pathways and suggest new mechanisms. Here, we adopt this method to investigate
      the chemical evolution of the benzyl radical, whose role is very important in
      PAHs growth. This species has been intensely studied, and though most of its
      chemistry is known, there are still open questions regarding its decomposition.
      The simulation reproduces the most commonly accepted decomposition pathway and it
      suggests also a new one which can explain recent experimental data that are in
      contradiction with the old mechanism. In addition, quantitative free energy
      evaluation of some key reaction steps sheds light on the role of entropy. 

PMID- 25587629
TI  - Corona-directed nucleic acid delivery into hepatic stellate cells for liver
      fibrosis therapy.
AB  - Strategies to modify nanoparticles with biological ligands for targeted drug
      delivery in vivo have been widely studied but met with limited clinical success.
      A possible reason is that, in the blood circulation, serum proteins could rapidly
      form a layer of protein "corona" on the vehicle surface, which might block the
      modified ligands and hamper their targeting functions. We speculate that
      strategies for drug delivery can be designed based upon elegant control of the
      corona formation on the vehicle surfaces. In this study, we demonstrate a retinol
      conjugated polyetherimine (RcP) nanoparticle system that selectively recruited
      the retinol binding protein 4 (RBP) in its corona components. RBP was found to
      bind retinol, and direct the antisense oligonucleotide (ASO)-laden RcP carrier to
      hepatic stellate cells (HSC), which play essential roles in the progression of
      hepatic fibrosis. In both mouse fibrosis models, induced by carbon tetrachloride
      (CCl4) and bile duct ligation (BDL), respectively, the ASO-laden RcP particles
      effectively suppressed the expression of type I collagen (collagen I), and
      consequently ameliorated hepatic fibrosis. Such findings suggest that this
      delivery system, designed to exploit the power of corona proteins, can serve as a
      promising tool for targeted delivery of therapeutic agents for the treatment of
      hepatic fibrosis. 

PMID- 25587631
TI  - Pachymodulin, a new functional formyl peptide receptor 2 peptidic ligand isolated
      from frog skin has Janus-like immunomodulatory capacities.
AB  - Recruitment of leukocytes is essential to fight infections or to heal injuries;
      however, excessive and/or prolonged responses favor the development of major
      inflammatory pathologies, such as cardiovascular or neurodegenerative diseases.
      Thus, it is of great interest to seek novel compounds that can regulate leukocyte
      recruitment depending on the degree of inflammation. We have isolated and
      characterized, by different chromatographic techniques, mass spectrometry, and
      Edman sequencing, a new hexapeptide (SSLSKL) from the Mexican frog Pachymedusa
      dacnicolor, which we named pachymodulin. In vitro, pachymodulin promotes the
      migration of leukocytes through the binding and activation of the human and mouse
      N-formyl peptide receptor 2 (huFPR2). In vivo, it exhibits opposite biological
      activities: under homeostatic conditions, pachymodulin induces the recruitment of
      leukocytes, whereas under inflammatory conditions, it inhibits this process.
      Therefore, pachymodulin represents an interesting template in the quest to design
      new immunomodulatory drugs in the therapy of immune-related diseases. 

PMID- 25587632
TI  - Combined biofouling and scaling in membrane feed channels: a new modeling
      approach.
AB  - A mathematical model was developed for combined fouling due to biofilms and
      mineral precipitates in membrane feed channels with spacers. Finite element
      simulation of flow and solute transport in two-dimensional geometries was coupled
      with a particle-based approach for the development of a composite (cells and
      crystals) foulant layer. Three fouling scenarios were compared: biofouling only,
      scaling only and combined fouling. Combined fouling causes a quicker flux decline
      than the summed flux deterioration when scaling and biofouling act independently.
      The model results indicate that the presence of biofilms leads to more mineral
      formation due to: (1) an enhanced degree of saturation for salts next to the
      membrane and within the biofilm; and (2) more available surface for nucleation to
      occur. The impact of biofilm in accelerating gypsum precipitation depends on the
      composition of the feed water (eg the presence of NaCl) and the kinetics of
      crystal nucleation and growth. Interactions between flow, solute transport and
      biofilm-induced mineralization are discussed. 

PMID- 25587633
TI  - Preparation and properties of ion-imprinted hollow particles for the selective
      adsorption of silver ions.
AB  - Four kinds of silver ion-imprinted particles (Ag-IIPs) with different
      morphologies were prepared by the surface ion-imprinting technology (SIIT) and
      were used for the selective removal and concentration of silver ions from
      wastewater. The favorable adsorptivity and selectivity of Ag-IIPs for Ag(+) were
      confirmed by a series of adsorption experiments at a suitable pH value. The
      adsorption mechanism was elucidated by analyzing the adsorption isotherms,
      adsorption thermodynamics, and adsorption kinetics systematically. The Ag(+)
      adsorption onto the Ag-IIPs was well-described by the Langmuir isotherm model,
      and it was likely to be a monolayer chemical adsorption. This conclusion was also
      confirmed by the thermodynamic parameters. Moreover, the adsorption kinetics
      indicated that the adsorption rate would be controlled jointly by the
      intraparticle diffusion and the inner surface adsorption process, and the latter
      process was generally associated with the formation and breaking of chemical
      bonds. Finally, the effects of different morphologies of the Ag-IIPs for Ag(+)
      adsorption were also investigated. In aqueous solution, the adsorptivity of the
      Ag(+) ion-imprinting single-hole hollow particles (Ag-IISHPs) for Ag(+) was
      highest (80.5 mg g(-1)) because of a specific morphology that features a single
      hole in the shell. In an oil-water mixture, Ag(+) in the water phase could be
      adsorbed efficiently by the Ag(+) ion-imprinting Janus hollow particles (Ag
      IIJHPs), with emulsifiability originating from the Janus structure. 

PMID- 25587634
TI  - Effects of biological and non-biological immunomodulatory therapies on the
      immunogenicity of vaccines in patients with rheumatic diseases.
AB  - Vaccinations are administered to patients to induce a protective immune response,
      resulting in immunological memory. Preventing infection through the use of
      vaccines is particularly important in immunocompromised and immunosuppressed
      individuals given their increased frequency and severity of infections relative
      to healthy individuals. Recent surveys show that the vaccination rate is still
      alarmingly low in patients with rheumatic disease. In this review we briefly
      discuss the different types of vaccines and then critically examine evidence
      related to vaccination efficacy in patients with autoimmune disease and the
      effects of immunomodulatory therapy, with an aim to provide guidance and optimize
      the administration of vaccines in such individuals. 

PMID- 25587636
TI  - Low-temperature plasma ionization-mass spectrometry for the analysis of compounds
      in organic aerosol particles.
AB  - Low-temperature plasma ionization, a technique that causes minimal fragmentation
      during ionization, is investigated as an ionization technique for mass
      spectrometric detection of the compounds in ambient organic aerosols in real
      time. The experiments presented in this paper demonstrate that ions are generated
      from compounds in the aerosol particles. The utility of this technique for
      detection of both positive and negative ions from the pyrolysate of multiple
      natural polymers is presented. Ultimately, low-temperature plasma ionization is
      shown to be a promising ionization technique for detection of compounds in
      organic aerosols by mass spectrometry. 

PMID- 25587637
TI  - Phytochemical Characterization, Antimicrobial Activity, and Antioxidant Potential
      of Equisetum hyemale L. (Equisetaceae) Extracts.
AB  - Equisetum hyemale species is considered a medicinal plant used in the form of
      infusions to combat infectious or inflammation diseases and also diuretic
      effects, presenting several compounds related to these actions. In previous
      studies different species of Equisetum showed several phenolic compounds. The
      objective of this study was, for the first time, based on phytochemistry analysis
      to evaluate the antioxidant and antimicrobial activity. The 70% ethanolic and
      methanolic extracts of E. hyemale were characterized by spectrophotometric and
      high-performance liquid chromatography with pulsed amperometric detector
      analyses, as well as its antioxidant potential based on the scavenger activity of
      2,2-diphenyl-1-picrylhydrazyl (DPPH). In addition was verified the antimicrobial
      activity by broth microdilution technique against bacteria and fungi. The
      extracts showed phytochemical similarity, which demonstrated the presence of
      phenolic compounds, the scavenging activity for free radicals was about 30% and
      was observed better antifungal activity against dermatophyte fungi, with minimum
      inhibitory concentration and minimum fungicidal concentration of 0.62 mg/mL to
      Trichophyton rubrum and Microsporum canis. The extracts exhibits great potential
      to therapeutic applications or product development, since both possess antifungal
      activity and antioxidant action associated with little difference in their
      phytochemical composition. 

PMID- 25587641
TI  - Hypoxic pulmonary vasoconstriction: physiology and anesthetic implications.
AB  - Hypoxic pulmonary vasoconstriction (HPV) represents a fundamental difference
      between the pulmonary and systemic circulations. HPV is active in utero, reducing
      pulmonary blood flow, and in adults helps to match regional ventilation and
      perfusion although it has little effect in healthy lungs. Many factors affect HPV
      including pH or PCO2, cardiac output, and several drugs, including
      antihypertensives. In patients with lung pathology and any patient having one
      lung ventilation, HPV contributes to maintaining oxygenation, so
      anesthesiologists should be aware of the effects of anesthesia on this protective
      reflex. Intravenous anesthetic drugs have little effect on HPV, but it is
      attenuated by inhaled anesthetics, although less so with newer agents. The reflex
      is biphasic, and once the second phase becomes active after about an hour of
      hypoxia, this pulmonary vasoconstriction takes hours to reverse when normoxia
      returns. This has significant clinical implications for repeated periods of one
      lung ventilation. 

PMID- 25587643
TI  - Efficient hybrid mesoscopic solar cells with morphology-controlled CH3NH3PbI3
      xClx derived from two-step spin coating method.
AB  - A morphology-controlled CH3NH3PbI3-xClx film is synthesized via two-step solution
      deposition by spin-coating a mixture solution of CH3NH3Cl and CH3NH3I onto the
      TiO2/PbI2 film for the first time. It is revealed that the existence of CH3NH3Cl
      is supposed to result in a preferential growth along the [110] direction of
      perovskite, which can improve both the crystallinity and surface coverage of
      perovskite and reduce the pinholes. Furthermore, the formation process of
      CH3NH3PbI3-xClx perovskite is explored, in which intermediates containing
      chlorine are suggested to exist. 13.12% of power conversion efficiency has been
      achieved for the mesoscopic cell, higher than 12.08% of power conversion
      efficiency of the devices fabricated without CH3NH3Cl via the same process. The
      improvement mainly lies in the increasing open-circuit photovoltage which is
      ascribed to the reduction of reverse saturation current density. 

PMID- 25587642
TI  - Optimal cutoffs of obesity measures in relation to cancer risk in postmenopausal
      women in the Women's Health Initiative Study.
AB  - BACKGROUND: Obesity is a risk factor for several cancers in postmenopausal women.
      We attempted to determine cutoffs of adiposity measures in relation to risk of
      obesity-related cancers among postmenopausal women and to examine the effects of
      hormone therapy (HT) use on the cutoffs, neither of which has been broadly
      studied. METHODS: We used data from the Women's Health Initiative cohort
      (n=144,701) and applied Cox-proportional hazards regressions to each combination
      of 17 cancer types and 6 anthropometric measures (weight, body mass index [BMI],
      weight to height ratio, waist circumference, waist to hip ratio [WHR], and waist
      to height ratio). Interactions between the anthropometric measures and HT use
      were also examined. Cutoffs were determined by applying a grid search followed by
      a two-fold cross validation method. Survival ROC analysis of 5- and 10-year
      incidence followed. RESULTS: Breast, colorectal, colon, endometrium, kidney, and
      all cancers combined were significantly positively associated with all six
      anthropometric measures, whereas lung cancer among ever smokers was significantly
      inversely associated with all measures except WHR. The derived cutoffs of each
      obesity measure varied across cancers (e.g., BMI cutoffs for breast and
      endometrium cancers were 30 kg/m(2) and 34 kg/m(2), respectively), and also
      depended on HT use. The Youden indices of the cutoffs for predicting 5- and 10
      year cancer incidence were higher among HT never users. CONCLUSION: Using a panel
      of different anthropometric measures, we derived optimal cut-offs categorizing
      populations into high- and low-risk groups, which differed by cancer type and HT
      use. Although the discrimination abilities of these risk categories were
      generally poor, the results of this study could serve as a starting point from
      which to determine adiposity cutoffs for inclusion in risk prediction models for
      specific cancer types.

PMID- 25587644
TI  - Iodide, bromide, and ammonium in hydraulic fracturing and oil and gas
      wastewaters: environmental implications.
AB  - The expansion of unconventional shale gas and hydraulic fracturing has increased
      the volume of the oil and gas wastewater (OGW) generated in the U.S. Here we
      demonstrate that OGW from Marcellus and Fayetteville hydraulic fracturing
      flowback fluids and Appalachian conventional produced waters is characterized by
      high chloride, bromide, iodide (up to 56 mg/L), and ammonium (up to 420 mg/L).
      Br/Cl ratios were consistent for all Appalachian brines, which reflect an origin
      from a common parent brine, while the I/Cl and NH4/Cl ratios varied among brines
      from different geological formations, reflecting geogenic processes. There were
      no differences in halides and ammonium concentrations between OGW originating
      from hydraulic fracturing and conventional oil and gas operations. Analysis of
      discharged effluents from three brine treatment sites in Pennsylvania and a spill
      site in West Virginia show elevated levels of halides (iodide up to 28 mg/L) and
      ammonium (12 to 106 mg/L) that mimic the composition of OGW and mix
      conservatively in downstream surface waters. Bromide, iodide, and ammonium in
      surface waters can impact stream ecosystems and promote the formation of toxic
      brominated-, iodinated-, and nitrogen disinfection byproducts during chlorination
      at downstream drinking water treatment plants. Our findings indicate that
      discharge and accidental spills of OGW to waterways pose risks to both human
      health and the environment. 

PMID- 25587645
TI  - Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to
      severe binge-eating disorder: a randomized clinical trial.
AB  - IMPORTANCE: Binge-eating disorder (BED), a public health problem associated with
      psychopathological symptoms and obesity and possibly with metabolic syndrome,
      lacks approved pharmacotherapies. OBJECTIVE: To examine the efficacy and safety
      of lisdexamfetamine dimesylate, a dextroamphetamine prodrug, to treat moderate to
      severe BED. DESIGN, SETTING, AND PARTICIPANTS: We performed a randomized, double
      blind, parallel-group, forced dose titration, placebo-controlled clinical trial
      at 30 sites from May 10, 2011, through January 30, 2012. Safety and intention-to
      treat analyses included 259 and 255 adults with BED, respectively. INTERVENTIONS:
      Lisdexamfetamine dimesylate at dosages of 30, 50, or 70 mg/d or placebo were
      provided to study participants (1:1:1:1). Dosages were titrated across 3 weeks
      and maintained for 8 weeks. We followed up participants for a mean (SD) of 7 (2)
      days after the last dose. MAIN OUTCOMES AND MEASURES: We assessed the change in
      binge-eating (BE) behaviors measured as days per week (baseline to week 11) with
      a mixed-effects model using transformed log (BE days per week) + 1. Secondary
      measures included BE cessation for 4 weeks. Safety assessments included treatment
      emergent adverse events, vital signs, and change in weight. RESULTS: At week 11,
      log-transformed BE days per week decreased with the 50-mg/d (least squares [LS]
      mean [SE] change, -1.49 [0.066]; P = .008) and 70-mg/d (LS mean [SE] change, 
      1.57 [0.067]; P < .001) treatment groups but not the 30-mg/d treatment group (LS
      mean [SE] change, -1.24 [0.067]; P = .88) compared with the placebo group.
      Nontransformed mean (SD) days per week decreased for placebo and the 30-, 50-,
      and 70-mg/d treatment groups by -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1
      (1.57), respectively. The percentage of participants achieving 4-week BE
      cessation was lower with the placebo group (21.3%) compared with the 50-mg/d
      (42.2% [P = .01]) and 70-mg/d (50.0% [P < .001]) treatment groups. The incidence
      of any treatment-emergent adverse events was 58.7% for the placebo group and
      84.7% for the combined treatment group. In the treatment groups, 1.5% of
      participants had serious treatment-emergent adverse effects. Events with a
      frequency of at least 5% and changes in heart rate were generally consistent with
      the known safety profile. The mean (SD) change in body weight was -0.1 (3.09), 
      3.1 (3.64), -4.9 (4.43), -4.9 (3.93), and -4.3 (4.09) kg for the placebo group,
      the 30-, 50-, and 70-mg/d treatment groups, and the combined treatment groups,
      respectively (P < .001 for each dose vs placebo group comparison in post hoc
      analysis). CONCLUSIONS AND RELEVANCE: The 50- and 70-mg/d treatment groups
      demonstrated efficacy compared with the placebo group in decreased BE days, BE
      cessation, and global improvement. The safety profile was generally consistent
      with previous findings in adults with attention-deficit/hyperactivity disorder.
      Further investigation of lisdexamfetamine in BED is ongoing. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01291173.

PMID- 25587646
TI  - The proportion of diploid 46,XX cells increases with time in women with Turner
      syndrome--a 10-year follow-up study.
AB  - In the normal population, loss of one of the sex chromosomes leading to monosomy
      (45,X) is a part of the aging process. In Turner syndrome (TS), the classic
      karyotype 45,X is found in up to 50% at birth, and others have a second cell
      line; mosaicism. The aim was to study if the chromosomal pattern in TS women
      changes over time. Fluorescence in situ hybridization was performed on buccal
      smear cells obtained twice, 10 years apart, from 42 women with TS aged 26-66
      years (mean+/-standard deviation: 42.0+/-11.6). DNA probes specific for
      chromosomes X (DXZ1) and Y (DYZ3) were used and >100 cells were analyzed/patient.
      Nineteen women had monosomy (45,X) (<10% 46,XX), nine had 45,X/46,XX mosaicism,
      and 14 had iso, ring, or a marker chromosome at baseline. At 10 years, the
      percentage of diploid cells had increased in 29 of 42 women (69%), with an
      average increase of 5.7+/-13.0%. There was a positive correlation between age and
      % change in diploid 46,XX or 46,XY cells (r=0.38, p=0.023). This new finding
      might have relevance for the life expectancy in TS. 

PMID- 25587647
TI  - Targeting HER2 for the treatment of breast cancer.
AB  - HER2 (ErbB2), a member of the HER family of tyrosine kinase receptors (HER1-4),
      is a major driver of tumor growth in 20% of breast cancers. Treatment with the
      anti-HER2 monoclonal antibody trastuzumab has revolutionized the outcome of
      patients with this aggressive breast cancer subtype, but intrinsic and acquired
      resistance is common. Growing understanding of the biology and complexity of the
      HER2 signaling network and of potential resistance mechanisms has guided the
      development of new HER2-targeted agents. Combinations of these drugs to more
      completely inhibit the HER receptor layer, or combining HER2-targeted agents with
      agents that target downstream signaling, alternative pathways, or components of
      the host immune system, are being vigorously investigated in the preclinical and
      clinical settings. As a result, the list of more effective and well tolerated FDA
      approved new regimens for patients with HER2+ tumors is constantly growing. 

PMID- 25587649
TI  - Advances in nanoparticle imaging technology for vascular pathologies.
AB  - Nanoparticle imaging agents for vascular pathologies are in development, and some
      agents are already in clinical trials. Untargeted agents, with long circulation,
      are excellent blood-pool agents, but molecularly targeted agents have significant
      advantages due to the signal enhancement possible with nanoparticle presentation
      of the contrast agent molecules. Molecular targets that are accessible directly
      from the vasculature are optimal for such agents. Targets that are removed from
      the vasculature, such as those on tumor cell surfaces, have limited accessibility
      owing to the enhanced permeation and retention effect. Yet, efforts at molecular
      targeting have tested small molecules, peptides, antibodies, and most recently
      aptamers as possible targeting ligands. The future is bright for nanoparticle
      based imaging of vascular pathologies. 

PMID- 25587648
TI  - Cardiovascular disease in adult survivors of childhood cancer.
AB  - Treatment advances have increased survival in children with cancer, but
      subclinical, progressive, irreversible, and sometimes fatal treatment-related
      cardiovascular effects may appear years later. Cardio-oncologists have identified
      promising preventive and treatment strategies. Dexrazoxane provides long-term
      cardioprotection from doxorubicin-associated cardiotoxicity without compromising
      the efficacy of anticancer treatment. Continuous infusion of doxorubicin is as
      effective as bolus administration in leukemia treatment, but no evidence has
      indicated that it provides long-term cardioprotection; continuous infusions
      should be eliminated from pediatric cancer treatment. Angiotensin-converting
      enzyme inhibitors can delay the progression of subclinical and clinical
      cardiotoxicity. All survivors, regardless of whether they were treated with
      anthracyclines or radiation, should be monitored for systemic inflammation and
      the risk of premature cardiovascular disease. Echocardiographic screening must be
      supplemented with screening for biomarkers of cardiotoxicity and perhaps by
      identification of genetic susceptibilities to cardiovascular diseases; optimal
      strategies need to be identified. The health burden related to cancer treatment
      will increase as this population expands and ages. 

PMID- 25587651
TI  - Changing practice of anticoagulation: will target-specific anticoagulants replace
      warfarin?
AB  - The target-specific oral anticoagulants are a class of agents that inhibit factor
      Xa or thrombin. They are effective and safe compared to warfarin for the
      prevention of stroke and systemic embolism in patients with atrial fibrillation
      and for the treatment of venous thromboembolism, and they are comparable to low
      molecular-weight heparin for thromboprophylaxis after hip or knee arthroplasty.
      For other indications, however, such as the prevention of stroke in patients with
      mechanical heart valves, initial studies have been unfavorable for the newer
      agents, leaving warfarin the anticoagulant of choice. Further studies are needed
      before the target-specific anticoagulants can be recommended for patients with
      cancer-associated thrombosis or heparin-induced thrombocytopenia. Concerns also
      persist about difficulties with the laboratory assessment of anticoagulant effect
      and the lack of a specific reversal agent. For these reasons, we anticipate that
      the vitamin K antagonists will continue to be important anticoagulants for years
      to come. 

PMID- 25587650
TI  - ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura.
AB  - Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over
      half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized
      in the liver, and its main function is to cleave von Willebrand factor (VWF)
      anchored on the endothelial surface, in circulation, and at the sites of vascular
      injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of
      the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or
      acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly
      reduced (>20%) in other forms of thrombotic microangiopathy secondary to
      hematopoietic progenitor cell transplantation, infection, and disseminated
      malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains
      the initial treatment of choice to date, but novel therapeutics such as
      recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13
      deficiency has been shown to be a risk factor for the development of myocardial
      infarction, stroke, cerebral malaria, and preeclampsia. 

PMID- 25587652
TI  - Extranuclear steroid receptors are essential for steroid hormone actions.
AB  - Steroid hormones are produced throughout the phylogenetic tree, from plants to
      mammals. In the past 40 years, steroid receptors localized to the nucleus have
      been recognized as being important to mediating steroid action in many organs.
      This action mainly arises from the regulation of key genes that are important for
      organ development and function. These include but are not limited to genes
      influencing the reproductive tract, mammary glands, bone, brain, fat
      differentiation, pituitary hormone regulation, and metabolic effects in many
      organs. Unfortunately, steroids also promote the development of hormone
      responsive cancers, including breast, uterus, and prostate cancer. It has also
      been shown that steroid receptors exist outside the nucleus in many organs and
      cells, with unclear impact for normal development, health, and disease. This
      review describes the evidence from many laboratories that these receptors exist
      and function with nuclear receptors to provide the full impact of all steroid
      hormones. 

PMID- 25587653
TI  - Obesity and cancer: local and systemic mechanisms.
AB  - Obesity is a leading modifiable risk factor for the development of several
      epithelial malignancies. In addition to increasing risk, obesity also confers
      worse prognosis for many cancers. Obesity represents an overall state of energy
      imbalance frequently associated with systemic effects including insulin
      resistance, altered hormone signaling, and high circulating levels of
      proinflammatory mediators. In addition to its systemic effects, obesity causes
      subclinical white adipose inflammation including increased tissue levels of
      proinflammatory mediators. Both local and systemic effects are likely to
      contribute to the development and progression of cancer. An understanding of the
      interplay between local and systemic alterations involved in the obesity-cancer
      link provides the basis for developing interventions aimed at mitigating the
      protumorigenic effects. 

PMID- 25587654
TI  - The JAK-STAT pathway: impact on human disease and therapeutic intervention.
AB  - The Janus kinase (JAK)-signal transducer of activators of transcription (STAT)
      pathway is now recognized as an evolutionarily conserved signaling pathway
      employed by diverse cytokines, interferons, growth factors, and related
      molecules. This pathway provides an elegant and remarkably straightforward
      mechanism whereby extracellular factors control gene expression. It thus serves
      as a fundamental paradigm for how cells sense environmental cues and interpret
      these signals to regulate cell growth and differentiation. Genetic mutations and
      polymorphisms are functionally relevant to a variety of human diseases,
      especially cancer and immune-related conditions. The clinical relevance of the
      pathway has been confirmed by the emergence of a new class of therapeutics that
      targets JAKs. 

PMID- 25587656
TI  - Treatment of recurrent and severe Clostridium difficile infection.
AB  - Clostridium difficile infection (CDI) is a serious complication of
      hospitalization and antibiotic use with a high mortality and very high costs.
      Despite appropriate treatment, a subset of patients develop chronic recurrent
      CDI. Some other patients develop severe and life-threatening colitis. The risk
      factors, pathogenesis, and treatment of recurrent CDI and severe CDI are
      discussed in this review. In particular, fecal microbiota transplantation (FMT)
      as a treatment strategy is outlined and a treatment algorithm incorporating FMT
      is described. 

PMID- 25587655
TI  - The gut microbial endocrine organ: bacterially derived signals driving
      cardiometabolic diseases.
AB  - The human gastrointestinal tract is home to trillions of bacteria, which vastly
      outnumber host cells in the body. Although generally overlooked in the field of
      endocrinology, gut microbial symbionts organize to form a key endocrine organ
      that converts nutritional cues from the environment into hormone-like signals
      that impact both normal physiology and chronic disease in the human host. Recent
      evidence suggests that several gut microbial-derived products are sensed by
      dedicated host receptor systems to alter cardiovascular disease (CVD)
      progression. In fact, gut microbial metabolism of dietary components results in
      the production of proatherogenic circulating factors that act through a meta
      organismal endocrine axis to impact CVD risk. Whether pharmacological
      interventions at the level of the gut microbial endocrine organ will reduce CVD
      risk is a key new question in the field of cardiovascular medicine. Here we
      discuss the opportunities and challenges that lie ahead in targeting meta
      organismal endocrinology for CVD prevention. 

PMID- 25587658
TI  - Lysosomal storage diseases: from pathophysiology to therapy.
AB  - Lysosomal storage diseases are a group of rare, inborn, metabolic errors
      characterized by deficiencies in normal lysosomal function and by intralysosomal
      accumulation of undegraded substrates. The past 25 years have been characterized
      by remarkable progress in the treatment of these diseases and by the development
      of multiple therapeutic approaches. These approaches include strategies aimed at
      increasing the residual activity of a missing enzyme (enzyme replacement therapy,
      hematopoietic stem cell transplantation, pharmacological chaperone therapy and
      gene therapy) and approaches based on reducing the flux of substrates to
      lysosomes. As knowledge has improved about the pathophysiology of lysosomal
      storage diseases, novel targets for therapy have been identified, and innovative
      treatment approaches are being developed. 

PMID- 25587659
TI  - From de novo mutations to personalized therapeutic interventions in autism.
AB  - The high heritability, early age at onset, and reproductive disadvantages of
      autism spectrum disorders (ASDs) are consistent with an etiology composed of
      dominant-acting de novo (spontaneous) mutations. Mutation detection by microarray
      analysis and DNA sequencing has confirmed that de novo copy-number variants or
      point mutations in protein-coding regions of genes contribute to risk, and some
      of the underlying causal variants and genes have been identified. As our
      understanding of autism genes develops, the spectrum of autism is breaking up
      into quanta of many different genetic disorders. Given the diversity of
      etiologies and underlying biochemical pathways, personalized therapy for ASDs is
      logical, and clinical genetic testing is a prerequisite. 

PMID- 25587660
TI  - Social networks, social media, and innovating surgical education.

PMID- 25587657
TI  - Understanding HIV latency: the road to an HIV cure.
AB  - Treatment with antiretroviral therapy dramatically increases the survival of HIV
      infected individuals. However, treatment has to be continued for life because it
      does not lead to the full eradication of infection. HIV persists in resting
      CD4(+) T cells, and possibly other cell types, and can reemerge from these cells
      when therapy is interrupted. Here, we review molecular mechanisms that have been
      proposed to contribute to HIV latency, as well as the relative roles of cis- and
      trans-acting mechanisms. We also discuss existing and future therapeutic
      opportunities regarding HIV latency that might lead to a future cure for HIV
      infection. 

PMID- 25587661
TI  - Postmorbid learning of saxophone playing in a patient with frontotemporal
      dementia.
AB  - Some patients with frontotemporal dementia (FTD) show an artistic enhancement of
      musical abilities. However, no patients with FTD, to date, have been reported to
      be able to learn how to play a musical instrument after disease onset. Herein we
      describe a patient (J. K.) who had never played any musical instruments
      premorbidly, but who learned to play the saxophone after being diagnosed with a
      behavioral variant of FTD. He mastered a repertoire that consisted of 10 pieces
      of Korean folk songs over a period of three years. Furthermore, his saxophone
      skills were high enough to outperform other students in his class. 

PMID- 25587664
TI  - Mild and selective Et2Zn-catalyzed reduction of tertiary amides under
      hydrosilylation conditions.
AB  - Diethylzinc (Et2Zn) can be used as an efficient and chemoselective catalyst for
      the reduction of tertiary amides under mild reaction conditions employing cost
      effective polymeric silane (PMHS) as the hydride source. Crucial for the
      catalytic activity was the addition of a substoichiometric amount of lithium
      chloride to the reaction mixture. A series of amides containing different
      additional functional groups were reduced to their corresponding amines, and the
      products were isolated in good-to-excellent yields. 

PMID- 25587663
TI  - Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic
      strategy in ovarian cancer.
AB  - Plasminogen activator inhibitor (PAI)-1 is predictive of poor outcome in several
      types of cancer. The present study investigated the biological role for PAI-1 in
      ovarian cancer and potential of targeted pharmacotherapeutics. In patients with
      ovarian cancer, PAI-1 mRNA expression in tumor tissues was positively correlated
      with poor prognosis. To determine the role of PAI-1 in cell proliferation in
      ovarian cancer, the effects of PAI-1 inhibition were examined in PAI-1-expressing
      ovarian cancer cells. PAI-1 knockdown by small interfering RNA resulted in
      significant suppression of cell growth accompanied with G2/M cell cycle arrest
      and intrinsic apoptosis. Similarly, treatment with the small molecule PAI-1
      inhibitor TM5275 effectively blocked cell proliferation of ovarian cancer cells
      that highly express PAI-1. Together these results suggest that PAI-1 promotes
      cell growth in ovarian cancer. Interestingly, expression of PAI-1 was increased
      in ovarian clear cell carcinoma compared with that in serous tumors. Our results
      suggest that PAI-1 inhibition promotes cell cycle arrest and apoptosis in ovarian
      cancer and that PAI-1 inhibitors potentially represent a novel class of anti
      tumor agents. 

PMID- 25587665
TI  - The squid ink polysaccharides protect tight junctions and adherens junctions from
      chemotherapeutic injury in the small intestinal epithelium of mice.
AB  - Gastrointestinal mucositis and infection by chemotherapy treatment are associated
      with alterations in the functioning of the intestinal barrier, due to the
      potential damage induced by anticancer drugs on the epithelial tight junctions
      and adheren junction. We aimed to study the protective effect of dietary
      polysaccharides on chemotherapy-induced injury in the epithelial cells. In the
      current study, using mice that were intraperitoneally injected with 50 mg/kg
      cyclophosphamide for 2 days, we reveal that polysaccharides from the ink of
      Ommastrephes bartrami (OBP) enhanced the mRNA and protein expression levels of
      Occludin, zonulae occluden (ZO)-1, and E-cadherin. Immunohistochemistry staining
      of ZO-1 and E-cadherin confirmed the increase in the mRNA and protein levels. OBP
      also remarkably enhanced the mRNA expression of other tight junction proteins, ZO
      2, ZO-3, claudin-2, and cingulin. Our results may have important implications in
      host defense, especially the immunopotentiation function of OBP on the
      cyclophosphamide-induced epithelial cell injury, as well as intestinal disorders
      involving inflammation and infection.

PMID- 25587666
TI  - Peripheral Hearing and Cognition: Evidence From the Staying Keen in Later Life
      (SKILL) Study.
AB  - OBJECTIVES: Research has increasingly suggested a consistent relationship between
      peripheral hearing and selected measures of cognition in older adults. However,
      other studies yield conflicting findings. The primary purpose of the present
      study was to further elucidate the relationship between peripheral hearing and
      three domains of cognition and one measure of global cognitive status. It was
      hypothesized that peripheral hearing loss would be significantly associated with
      poorer performance across measures of cognition, even after adjusting for
      documented risk factors. No study to date has examined the relationship between
      peripheral hearing and such an extensive array of cognitive measures. DESIGN:
      Eight hundred ninety-four older adult participants from the Staying Keen in Later
      Life study cohort were eligible, agreed to participate, and completed the
      baseline evaluation. Inclusion criteria were minimal to include a sample of older
      adults with a wide range of sensory and cognitive abilities. Multiple linear
      regression analyses were conducted to evaluate the extent to which peripheral
      hearing predicted performance on a global measure of cognitive status, as well as
      multiple cognitive measures in the domains of speed of processing (Digit Symbol
      Substitution and Copy, Trail Making Test Part A, Letter and Pattern Comparison,
      and Useful Field of View), executive function (Trail Making Test Part B and
      Stroop Color-Word Interference Task), and memory (Digit Span, Spatial Span, and
      Hopkins Verbal Learning Test). RESULTS: Peripheral hearing, measured as the three
      frequency pure-tone average (PTA) in the better ear, accounted for a significant,
      but minimal, amount of the variance in measures of speed of processing, executive
      function, and memory, as well as global cognitive status. Alternative measures of
      hearing (i.e., three-frequency PTAs in the right and left ears and a bilateral,
      six-frequency PTA [three frequencies per ear]) yielded similar findings across
      measures of cognition and did not alter the study outcomes in any meaningful way.
      CONCLUSIONS: Consistent with literature suggesting a significant relationship
      between peripheral hearing and cognition, and in agreement with our hypothesis,
      peripheral hearing was significantly related to 10 of 11 measures of cognition
      that assessed processing speed, executive function, or memory, as well as global
      cognitive status. Although evidence, including the present results, suggests a
      relationship between peripheral hearing and cognition, little is known about the
      underlying mechanisms. Examination of these mechanisms is a critical need to
      direct appropriate treatment.

PMID- 25587667
TI  - Automated Vocal Analysis of Children With Hearing Loss and Their Typical and
      Atypical Peers.
AB  - OBJECTIVES: This study investigated automatic assessment of vocal development in
      children with hearing loss compared with children who are typically developing,
      have language delays, and have autism spectrum disorder. Statistical models are
      examined for performance in a classification model and to predict age within the
      four groups of children. DESIGN: The vocal analysis system analyzed 1913 whole
      day, naturalistic acoustic recordings from 273 toddlers and preschoolers
      comprising children who were typically developing, hard of hearing, language
      delayed, or autistic. RESULTS: Samples from children who were hard of hearing
      patterned more similarly to those of typically developing children than to the
      language delayed or autistic samples. The statistical models were able to
      classify children from the four groups examined and estimate developmental age
      based on automated vocal analysis. CONCLUSIONS: This work shows a broad
      similarity between children with hearing loss and typically developing children,
      although children with hearing loss show some delay in their production of
      speech. Automatic acoustic analysis can now be used to quantitatively compare
      vocal development in children with and without speech-related disorders. The work
      may serve to better distinguish among various developmental disorders and
      ultimately contribute to improved intervention.

PMID- 25587669
TI  - Delayed Stream Segregation in Older Adults: More Than Just Informational Masking.
AB  - OBJECTIVE: To determine whether the time course for the buildup of auditory
      stream segregation differs between younger and older adults. DESIGN: Word
      recognition thresholds were determined for the first and last keywords in
      semantically anomalous but syntactically correct sentences (e.g., "A rose could
      paint a fish") when the target sentences were masked by speech-spectrum noise, 3
      band vocoded speech, 16-band vocoded speech, intact and colocated speech, and
      intact and spatially separated speech. A significant reduction in thresholds from
      the first to the last keyword was interpreted as indicating that stream
      segregation improved with time. RESULTS: The buildup of stream segregation is
      slowed for both age groups when the masker is intact, colocated speech.
      CONCLUSIONS: Older adults are more disadvantaged; for them, stream segregation is
      also slowed even when a speech masker is spatially separated, conveys little
      meaning (3-band vocoding), and vocal fine structure cues are impoverished but
      envelope cues remain available (16-band vocoding).

PMID- 25587668
TI  - Consensus on Hearing Aid Candidature and Fitting for Mild Hearing Loss, With and
      Without Tinnitus: Delphi Review.
AB  - OBJECTIVES: In many countries including the United Kingdom, hearing aids are a
      first line of audiologic intervention for many people with tinnitus and aidable
      hearing loss. Nevertheless, there is a lack of high quality evidence to support
      that they are of benefit for tinnitus, and wide variability in their use in
      clinical practice especially for people with mild hearing loss. The aim of this
      study was to identify a consensus among a sample of UK clinicians on the criteria
      for hearing aid candidature and clinical practice in fitting hearing aids
      specifically for mild hearing loss with and without tinnitus. This will allow
      professionals to establish clinical benchmarks and to gauge their practice with
      that used elsewhere. DESIGN: The Delphi technique, a systematic methodology that
      seeks consensus amongst experts through consultation using a series of iterative
      questionnaires, was used. A three-round Delphi survey explored clinical consensus
      among a panel of 29 UK hearing professionals. The authors measured panel
      agreement on 115 statements covering: (i) general factors affecting the decision
      to fit hearing aids, (ii) protocol-driven factors affecting the decision to fit
      hearing aids, (iii) general practice, and (iv) clinical observations. Consensus
      was defined as a priori >=70% agreement across the panel. RESULTS: Consensus was
      reached for 58 of the 115 statements. The broad areas of consensus were around
      factors important to consider when fitting hearing aids; hearing aid
      technology/features offered; and important clinical assessment to verify hearing
      aid fit (agreement of 70% or more). For patients with mild hearing loss, the
      greatest priority was given by clinicians to patient-centered criteria for
      fitting hearing aids: hearing difficulties, motivation to wear hearing aids, and
      impact of hearing loss on quality of life (chosen as top five by at least 64% of
      panelists). Objective measures were given a lower priority: degree of hearing
      loss and shape of the audiogram (chosen as top five by less than half of
      panelists). Areas where consensus was not reached were related to the use of
      questionnaires to predict and verify hearing aid benefit for both hearing and
      tinnitus; audiometric criteria for fitting hearing aids; and safety of using loud
      sounds when verifying hearing aid fitting when the patient has tinnitus
      (agreement of <70%). CONCLUSIONS: The authors identified practices that are
      considered important when recommending or fitting hearing aid for a patient with
      tinnitus. More importantly perhaps, they identified practical issues where there
      are divided opinions. Their findings inform the design of clinical trials and
      open up debate on the potential impact of practice differences on patient
      outcomes.

PMID- 25587670
TI  - The utility of Geographical Information Systems (GIS) in systems-oriented obesity
      intervention projects: the selection of comparable study sites for a quasi
      experimental intervention design--TX CORD.
AB  - BACKGROUND: The Texas Childhood Obesity Research Demonstration project (TX CORD)
      uses a systems-oriented approach to address obesity that includes individual and
      family interventions, community-level action, as well as environmental and policy
      initiatives. Given that randomization is seldom possible in community-level
      intervention studies, TX CORD uses a quasi-experimental design. Comparable
      intervention and comparison study sites are needed to address internal validity
      bias. METHODS: TX CORD was designed to be implemented in low-income, ethnically
      diverse communities in Austin and Houston, Texas. A three-stage Geographical
      Information System (GIS) methodology was used to establish and ascertain the
      comparability of the intervention and comparison study sites. Census tract (stage
      1) and school (stage 2) data were used to identify spatially exclusive geographic
      areas that were comparable. In stage 3, study sites were compared on demographic
      characteristics, socioeconomic status (SES), food assets, and physical activity
      (PA) assets. Student's t-test was used to examine significant differences between
      the selected sites. RESULTS: The methodology that was used resulted in the
      selection of catchment areas with demographic and socioeconomic characteristics
      that fit the target population: ethnically diverse population; lower-median
      household income; and lower home ownership rates. Additionally, the intervention
      and comparison sites were statistically comparable on demographic and SES
      variables, as well as food assets and PA assets. CONCLUSIONS: This GIS approach
      can provide researchers, program evaluators, and policy makers with useful tools
      for both research and practice. Area-level information that allows for robust
      understanding of communities can enhance analytical procedures in community
      health research and offer significant contributions in terms of community
      assessment and engagement.

PMID- 25587673
TI  - Formamidine hydrochloride as an amino surrogate: I2-catalyzed oxidative amidation
      of aryl methyl ketones leading to free (N-H) alpha-ketoamides.
AB  - A highly efficient molecular iodine catalyzed oxidative amidation of aryl methyl
      ketones with formamidine hydrochloride has been developed. This reaction
      represents a novel strategy for the synthesis of free (N-H) alpha-ketoamides.
      Based on the experimental results, a self-sequenced iodination/Kornblum
      oxidation/amidation/oxidation/decarbonylation mechanism was proposed. 

PMID- 25587672
TI  - Gender differences in treatment retention among individuals with co-occurring
      substance abuse and mental health disorders.
AB  - BACKGROUND: A significant number of individuals with co-occurring substance abuse
      and mental health disorders do not engage, stay, and/or complete residential
      treatment. Although prior research indicates that women and men differ in their
      substance abuse treatment experiences, our knowledge of individuals with co
      occurring substance abuse and mental health disorders as well as those attending
      private residential treatment is limited. OBJECTIVES: The purpose of this study
      is to examine gender differences on treatment retention for individuals with co
      occurring substance abuse and mental health disorders who participate in private
      residential treatment. METHODS: The participants were 1,317 individuals (539
      women and 778 men) with co-occurring substance abuse and mental health disorders
      receiving treatment at three private residential treatment centers. Bivariate
      analyses, life tables, and Cox regression (survival analyses) were utilized to
      examine gender effects on treatment retention, and identify factors that predict
      treatment retention for men and women. RESULTS: This study found that women with
      co-occurring disorders were more likely to stay longer in treatment when compared
      to men. The findings indicate the factors influencing length of stay differ for
      each gender, and include: type of substance used prior to admission; Addiction
      Severity Index Composite scores; and Readiness to Change/URICA scores. Age at
      admission was a factor for men only. CONCLUSIONS/IMPORTANCE: These findings can
      be incorporated to develop and initiate program interventions to minimize early
      attrition and increase overall retention in private residential treatment for
      individuals with co-occurring substance use and mental health disorders.

PMID- 25587671
TI  - Establishment of an oral infection model resembling the periodontal pocket in a
      perfusion bioreactor system.
AB  - Periodontal infection involves a complex interplay between oral biofilms,
      gingival tissues and cells of the immune system in a dynamic microenvironment. A
      humanized in vitro model that reduces the need for experimental animal models,
      while recapitulating key biological events in a periodontal pocket, would
      constitute a technical advancement in the study of periodontal disease. The aim
      of this study was to use a dynamic perfusion bioreactor in order to develop a
      gingival epithelial-fibroblast-monocyte organotypic co-culture on collagen
      sponges. An 11 species subgingival biofilm was used to challenge the generated
      tissue in the bioreactor for a period of 24 h. The histological and scanning
      electron microscopy analysis displayed an epithelial-like layer on the surface of
      the collagen sponge, supported by the underlying ingrowth of gingival
      fibroblasts, while monocytic cells were also found within the sponge mass.
      Bacterial quantification of the biofilm showed that in the presence of the
      organotypic tissue, the growth of selected biofilm species, especially
      Campylobacter rectus, Actinomyces oris, Streptococcus anginosus, Veillonella
      dispar, and Porphyromonas gingivalis, was suppressed, indicating a potential
      antimicrobial effect by the tissue. Multiplex immunoassay analysis of cytokine
      secretion showed that interleukin (IL)-1 beta, IL-2, IL-4, and tumor necrosis
      factor (TNF)-alpha levels in cell culture supernatants were significantly up
      regulated in presence of the biofilm, indicating a positive inflammatory response
      of the organotypic tissue to the biofilm challenge. In conclusion, this novel
      host-biofilm interaction organotypic model might resemble the periodontal pocket
      and have an important impact on the study of periodontal infections, by
      minimizing the need for the use of experimental animal models.

PMID- 25587674
TI  - Biosynthesis and function of extracellular glycans in cyanobacteria.
AB  - The cell surface of cyanobacteria is covered with glycans that confer versatility
      and adaptability to a multitude of environmental factors. The complex
      carbohydrates act as barriers against different types of stress and play a role
      in intra- as well as inter-species interactions. In this review, we summarize the
      current knowledge of the chemical composition, biosynthesis and biological
      function of exo- and lipo-polysaccharides from cyanobacteria and give an overview
      of sugar-binding lectins characterized from cyanobacteria. We discuss
      similarities with well-studied enterobacterial systems and highlight the unique
      features of cyanobacteria. We pay special attention to colony formation and EPS
      biosynthesis in the bloom-forming cyanobacterium, Microcystis aeruginosa. 

PMID- 25587676
TI  - Response to "Intralabyrinthine schwannomas: a case series with discussion of the
      diagnosis and management" by Bouchetemple P, Heathcote K, Tollard E, Choussy O,
      Dehesdin D, Marie JP. Otol Neurotol 2013;34(5):944-51.

PMID- 25587677
TI  - The challenge of studying TiO2 nanoparticle bioaccumulation at environmental
      concentrations: crucial use of a stable isotope tracer.
AB  - The ecotoxicity of nanoparticles (NPs) is a growing area of research with many
      challenges ahead. To be relevant, laboratory experiments must be performed with
      well-controlled and environmentally realistic (i.e., low) exposure doses.
      Moreover, when focusing on the intensively manufactured titanium dioxide (TiO2)
      NPs, sample preparations and chemical analysis are critical steps to meaningfully
      assay NP's bioaccumulation. To deal with these imperatives, we synthesized for
      the first time TiO2 NPs labeled with the stable isotope (47)Ti. Thanks to the
      (47)Ti labeling, we could detect the bioaccumulation of NPs in zebra mussels
      (Dreissena polymorpha) exposed for 1 h at environmental concentrations via water
      (7-120 MUg/L of (47)TiO2 NPs) and via their food (4-830 MUg/L of (47)TiO2 NPs
      mixed with 1 * 10(6) cells/mL of cyanobacteria) despite the high natural Ti
      background, which varied in individual mussels. The assimilation efficiency (AE)
      of TiO2 NPs by mussels from their diet was very low (AE = 3.0 +/- 2.7%)
      suggesting that NPs are mainly captured in mussel gut, with little penetration in
      their internal organs. Thus, our methodology is particularly relevant in
      predicting NP's bioaccumulation and investigating the factors influencing their
      toxicokinetics in conditions mimicking real environments.

PMID- 25587675
TI  - A novel chitosan-hydrogel-based nanoparticle delivery system for local inner ear
      application.
AB  - HYPOTHESIS: A chitosan-hydrogel-based nanoparticle (nanohydrogel) delivery system
      can be used to deliver therapeutic biomaterials across the round window membrane
      (RWM) into the inner ear in a mouse model. BACKGROUND: Delivering therapies to
      the inner ear has always been a challenge for the otolaryngologist. Advances in
      biomedical nanotechnology, increased understanding of the RWM diffusion
      properties, and discovery of novel therapeutic targets and agents, have all
      sparked interest in the controlled local delivery of drugs and biomaterials to
      the inner ear using nanoparticles (NPs). METHODS: Fluorescently-labeled liposomal
      NPs were constructed and loaded into a chitosan-based hydrogel to form a
      nanohydrogel, and in vitro studies were performed to evaluate its properties and
      release kinetics. Furthermore, the nanohydrogel was applied to the RWM of mice,
      and perilymph and morphologic analysis were performed to assess the NP delivery
      and distribution within the inner ear. RESULTS: NPs with an average diameter of
      160 nm were obtained. In vitro experiments showed that liposomal NPs can persist
      under physiologic conditions for at least two weeks without significant
      degradation and that the nanohydrogel can carry and release these NPs in a
      controlled and sustained manner. In vivo findings demonstrated that the
      nanohydrogel can deliver intact nanoparticles into the perilymphatic system and
      reach cellular structures in the scala media of the inner ear of our mouse model.
      CONCLUSION: Our study suggests that the nanohydrogel system has great potential
      to deliver therapeutics in a controlled and sustained manner from the middle ear
      to the inner ear without altering inner ear structures.

PMID- 25587681
TI  - A new wrinkle.

PMID- 25587682
TI  - Krokodil: from Russia with love.

PMID- 25587683
TI  - Josef Jadassohn: a dermatologic pioneer.

PMID- 25587678
TI  - Evaluation of cetuximab as a candidate for targeted alpha-particle radiation
      therapy of HER1-positive disseminated intraperitoneal disease.
AB  - Although the epidermal growth factor receptor (EGFR), also known as HER1, has
      been studied for over a decade, it continues to be a molecule of great interest
      and focus of investigators for development of targeted therapies. The marketed
      monoclonal antibody cetuximab binds to HER1, and thus might serve as the basis
      for creation of imaging or therapies that target this receptor. The potential of
      cetuximab as a vehicle for the delivery of alpha-particle radiation was
      investigated in an intraperitoneal tumor mouse model. The effective working dose
      of 10 MUCi of (212)Pb-cetuximab was determined from a dose (10-50 MUCi)
      escalation study. Toxicity, as indicated by the lack of animal weight loss, was
      not evident at the 10 MUCi dose of (212)Pb-cetuximab. A subsequent study
      demonstrated (212)Pb-cetuximab had a therapeutic efficacy similar to that of
      (212)Pb-trastuzumab (p = 0.588). Gemcitabine given 24 h prior to (212)Pb
      cetuximab increased the median survival from 174 d to 283 d, but carboplatin
      suppressed the effectiveness of (212)Pb-cetuximab. Notably, concurrent treatment
      of tumor-bearing mice with (212)Pb-labeled cetuximab and trastuzumab provided
      therapeutic benefit that was greater than either antibody alone. In conclusion,
      cetuximab proved to be an effective vehicle for targeting HER1-expressing tumors
      with alpha-radiation for the treatment of disseminated intraperitoneal disease.
      These studies provide further evidence that the multimodality therapy regimens
      may have greater efficacy and benefit in the treatment of cancer patients.

PMID- 25587684
TI  - Trending.

PMID- 25587685
TI  - Dermatologic etymology: primary morphology of skin lesions.

PMID- 25587686
TI  - Medical problems in the trenches.

PMID- 25587687
TI  - A championship quiz on sports-related dermatoses.

PMID- 25587689
TI  - Structure evolution of nanoparticulate Fe2O3.
AB  - The atomic structure and properties of nanoparticulate Fe2O3 are characterized
      starting from its smallest Fe2O3 building unit through (Fe2O3)n clusters to
      nanometer-sized Fe2O3 particles. This is achieved by combining global structure
      optimizations at the density functional theory level, molecular dynamics
      simulations by employing tailored, ab initio parameterized interatomic potential
      functions and experiments. With the exception of nearly tetrahedral, adamantane
      like (Fe2O3)2 small (Fe2O3)n clusters assume compact, virtually amorphous
      structures with little or no symmetry. For n = 2-5 (Fe2O3)n clusters consist
      mainly of two- and three-membered Fe-O rings. Starting from n = 5 they
      increasingly assume tetrahedral shape with the adamantane-like (Fe2O3)2 unit as
      the main building block. However, the small energy differences between different
      isomers of the same cluster-size make precise structural assignment for larger
      (Fe2O3)n clusters difficult. The tetrahedral morphology persists for Fe2O3
      nanoparticles with up to 3 nm in diameter. Simulated crystallization of larger
      nanoparticles with diameters of about 5 nm demonstrates pronounced melting point
      depression and leads to formation of epsilon-Fe2O3 single crystals with hexagonal
      morphology. This finding is in excellent agreement with the results obtained for
      Fe2O3 nanopowders generated by laser vaporization and provides the first direct
      indication that epsilon-Fe2O3 may be thermodynamically the most stable phase in
      this size regime. 

PMID- 25587688
TI  - Sexual risk behaviors increasing among adolescents over time: comparison of two
      cohorts in Spain.
AB  - Despite advances in treatment and prevention, HIV/AIDS remains a serious health
      and social problem. This study's objective is to examine sexual behavior, levels
      of knowledge, and attitudes toward HIV/AIDS between two cohorts in Spanish
      adolescents, and to analyze gender differences in these cohorts. Participants
      were 2132 adolescents between 15 and 18 years of age: 1222 in 2006 (43.2% boys)
      and 910 in 2012 (54.1% boys). The results indicate lower HIV knowledge and less
      favorable attitudes about HIV/AIDS in the 2012 cohort. In addition, adolescents
      from the 2012 cohort had their first sexual intercourse at an earlier age and
      have more sexual partners than those from the 2006 cohort. Compared to boys,
      girls engage in fewer risky behaviors, although they did not use condoms with
      their stable partner; girls tended to use condom less when they were in a stable
      relationship than boys. This study confirms the insufficiency of prevention
      campaigns as well as the need to improve the impact from programs that promote
      healthy sexual habits. Assuming comparability of cohorts, this study suggests
      increased risk of HIV/AIDS over time. 

PMID- 25587691
TI  - Laser-assisted photothermal heating of a plasmonic nanoparticle-suspended droplet
      in a microchannel.
AB  - The present article reports the numerical and experimental investigations on the
      laser-assisted photothermal heating of a nanoliter-sized droplet in a
      microchannel when plasmonic particles are suspended in the droplet. Plasmonic
      nanoparticles exhibit strong light absorption and scattering upon the excitation
      of localized surface plasmons (LSPs), resulting in intense and rapid photothermal
      heating in a microchannel. Computational models are implemented to theoretically
      verify the photothermal behavior of gold nanoshell (GNS) and gold nanorod (GNR)
      particles suspended in a liquid microdroplet. Experiments were conducted to
      demonstrate rapid heating of a sub-100 nL droplet up to 100  degrees C with high
      controllability and repeatability. The heating and cooling time to the steady
      state is on the order of 1 second, while cooling requires less time than heating.
      The effects of core parameters, such as nanoparticle structure, volumetric
      concentration, microchannel depth, and laser power density on heating are
      studied. The obtained results can be integrated into existing microfluidic
      technologies that demand accurate and rapid heating of microdroplets in a
      microchannel. 

PMID- 25587690
TI  - Macrophage-derived soluble CD163 level in young patients with Gaucher disease:
      relation to phenotypes, disease severity and complications.
AB  - OBJECTIVES: Bone and lung involvement are two major causes of morbidity in
      Gaucher disease (GD). The soluble form of CD163 (sCD163) is a valuable diagnostic
      biomarker for monitoring diseases with increased macrophage activation. We
      determined sCD163 levels in 30 children and adolescence with GD compared with 30
      healthy controls and assessed the relation to phenotypes, disease severity and
      complications. METHODS: Thirty GD patients (10 had type 1 and 20 had type 3) were
      studied stressing on skeletal, pulmonary or neurological manifestations, enzyme
      replacement therapy (ERT), hematological profile, plasma chitotriosidase
      activity, D-dimer and sCD163. Liver and spleen volumes and bone mineral density
      (BMD) were assessed. RESULTS: sCD163 levels were markedly elevated in patients
      compared with controls. D-dimer, chitotriosidase activity and sCD163 levels were
      significantly increased in type 3 GD patients compared with type 1. sCD163 was
      significantly elevated in GD patients with dysphagia, developmental delay,
      pulmonary hypertension risk or abnormal BMD (osteopenia/osteoporosis) than those
      without. GD patients receiving ERT every 2weeks had lower levels than those under
      ERT for more than 2weeks. sCD163 was positively correlated with age, disease
      duration, severity score index, D-dimer and chitotriosidase activity. The cutoff
      value of sCD163 at 9400ng/mL could differentiate GD patients with and without
      pulmonary hypertension risk with a sensitivity of 90% and specificity of 95%.
      CONCLUSIONS: sCD163 is a biomarker for the clinical assessment of macrophage
      proliferation and activity that would help in risk prediction of bone and lung
      involvement and monitoring treatment response.

PMID- 25587692
TI  - Skin Abnormalities in CHILD Syndrome Successfully Treated with Pathogenesis-based
      Therapy.

PMID- 25587693
TI  - A naturalistic retrospective review of weight gain in bipolar patients treated
      with second generation antipsychotics.

PMID- 25587694
TI  - Effects of clozapine on perceptual abnormalities and sensory gating: a
      preliminary cross-sectional study in schizophrenia.
AB  - The aim of the present study was to investigate the effect of second-generation
      antipsychotics (clozapine or another second-generation antipsychotic) on
      perceptual abnormalities related to sensory gating deficit. Although clozapine is
      known to improve sensory gating assessed neurophysiologically, we hypothesized
      that patients with schizophrenia treated with clozapine would report less
      perceptual abnormalities related to sensory gating deficit than patients treated
      with other second-generation antipsychotics do. Forty patients with a diagnosis
      of schizophrenia were investigated (10 patients treated with clozapine and 30
      patients treated with another second-generation antipsychotic drug). Perceptual
      abnormalities were assessed with the Sensory Gating Inventory. Sensory gating was
      assessed through electroencephalogram with the auditory event-related potential
      method by measuring P50 amplitude changes in a dual click conditioning-testing
      procedure. Patients treated with clozapine present normal sensory gating and
      report less perceptual abnormalities related to sensory gating than patients
      treated with other second-generation antipsychotics do. Although the cross
      sectional design of this study is limited because causal inferences cannot be
      clearly concluded, the present study suggests clinical and neurophysiological
      advantages of clozapine compared with other second-generation antipsychotics and
      provides a basis for future investigations on the effect of this treatment on
      perceptual abnormalities related to sensory gating deficit in patients with
      schizophrenia. 

PMID- 25587695
TI  - Spinal Reflexes During Postural Control Under Psychological Pressure.
AB  - This study investigated the effect of psychological pressure on spinal reflex
      excitability. Thirteen participants performed a balancing task by standing on a
      balance disk with one foot. After six practice trials, they performed one
      nonpressure and one pressure trial involving a performance-contingent cash reward
      or punishment. Stress responses were successfully induced; state anxiety, mental
      effort, and heart rates all increased under pressure. Soleus Hoffmann reflex
      amplitude in the pressure trial was significantly smaller than in the nonpressure
      trial. This modification of spinal reflexes may be caused by presynaptic
      inhibition under the control of higher central nerve excitation under pressure.
      This change did not prevent 12 of the 13 participants from successfully
      completing the postural control task under pressure. These results suggest that
      Hoffmann reflex inhibition would contribute to optimal postural control under
      stressful situations. 

PMID- 25587696
TI  - The snow, the men, the shovel, the risk? ER admissions after snow shovelling: 13
      winters in Bern.

PMID- 25587697
TI  - Bismuth oxyiodide nanosheets: a novel high-energy anode material for lithium-ion
      batteries.
AB  - BiOI nanosheets are easily synthesized by direct thermal treatment of commercial
      BiI3 powder, serving as a novel anode material for lithium-ion batteries. A high
      volumetric capacity of ~5678 mA h cm(-3) was achieved. This work demonstrates
      that the BiOI nanosheets hold great promise as high-energy anode material for
      lithium-ion batteries. 

PMID- 25587698
TI  - Hierarchical molecular dynamics of bovine serum albumin in concentrated aqueous
      solution below and above thermal denaturation.
AB  - The dynamics of proteins in solution is a complex and hierarchical process,
      affected by the aqueous environment as well as temperature. We present a
      comprehensive study on nanosecond time and nanometer length scales below, at, and
      above the denaturation temperature Td. Our experimental data evidence dynamical
      processes in protein solutions on three distinct time scales. We suggest a
      consistent physical picture of hierarchical protein dynamics: (i) self-diffusion
      of the entire protein molecule is confirmed to agree with colloid theory for all
      temperatures where the protein is in its native conformational state. At higher
      temperatures T > Td, the self-diffusion is strongly obstructed by cross-linking
      or entanglement. (ii) The amplitude of backbone fluctuations grows with
      increasing T, and a transition in its dynamics is observed above Td. (iii) The
      number of mobile side-chains increases sharply at Td while their average dynamics
      exhibits only little variations. The combination of quasi-elastic neutron
      scattering and the presented analytical framework provides a detailed microscopic
      picture of the protein molecular dynamics in solution, thereby reflecting the
      changes of macroscopic properties such as cluster formation and gelation. 

PMID- 25587699
TI  - The PAndemic INfluenza Triage in the Emergency Department (PAINTED) pilot cohort
      study.
AB  - BACKGROUND: Research needs to be undertaken rapidly in the event of an influenza
      pandemic to develop and evaluate triage methods for people presenting to the
      emergency department with suspected pandemic influenza. OBJECTIVES: We aimed to
      pilot a research study to be undertaken in a pandemic to identify the most
      accurate triage method for patients presenting to the emergency department with
      suspected pandemic influenza. The objectives of the pilot study were to develop a
      standardised clinical assessment form and secure online database; test both using
      data from patients with seasonal influenza; seek clinician views on the usability
      of the form; and obtain all regulatory approvals required for the main study.
      DESIGN: Study methods were piloted using an observational cohort study and
      clinician views were sought using qualitative, semistructured interviews.
      SETTING: Six acute hospital emergency departments. PARTICIPANTS: Patients
      attending the emergency department with suspected seasonal influenza during
      winter 2012-13 and clinicians working in the emergency departments. MAIN OUTCOME
      MEASURES: Adverse events up to 30 days were identified, but analysis of the pilot
      data was limited to descriptive reporting of patient flow, data completeness and
      patient characteristics. RESULTS: Some 165 patients were identified, of whom 10
      withdrew their data, leaving 155 (94%) for analysis. Follow-up data were
      available for 129 of 155 (83%), with 50 of 129 (39%) being admitted to hospital.
      Three cases (2%) were recorded as having suffered an adverse outcome. There
      appeared to be variation between the hospitals, allowing for small numbers. Three
      of the hospitals identified 150 of 165 (91%) of the patients, and all 10
      withdrawing patients were at the same hospital. The proportion with missing
      follow-up data varied from 8% to 31%, and the proportion admitted varied from 4%
      to 85% across the three hospitals with meaningful numbers of cases. All of the
      deaths were at one hospital. There was less variation between hospitals in rates
      of missing data, and for most key variables missing rates were between 5% and
      30%. Higher missing rates were recorded for blood pressure (39%), inspired oxygen
      (43%), capillary refill (36%) and Glasgow Coma Scale score (43%). Chest
      radiography was performed in 51 of 118 cases, and electrocardiography in 40 of
      111 cases with details recorded. Blood test results were available for 32 of 155
      cases. The qualitative interviews revealed generally positive views towards the
      standardised assessment form. Concerns about lack of space for free text were
      raised but counterbalanced by appreciation that it fitted on to one A4 page. A
      number of amendments were suggested but only three of these were suggested by
      more than one participant, and no suggestions were made by more than two
      participants. CONCLUSIONS: A standardised assessment form is acceptable to
      clinicians and could be used to collect research data in an influenza pandemic,
      but analysis may be limited by missing data. FUTURE WORK: An observational cohort
      study to identify the most accurate triage method for predicting severe illness
      in emergency department attendees with suspected pandemic influenza is set up and
      ready to activate if, or when, a pandemic occurs. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN56149622. FUNDING: This project was funded by the NIHR
      Health Technology Assessment programme and will be published in full in Health
      Technology Assessment; Vol. 19, No. 3. See the NIHR Journals Library website for
      further project information.

PMID- 25587700
TI  - The crystal structure of the versatile cytochrome P450 enzyme CYP109B1 from
      Bacillus subtilis.
AB  - The crystal structure of the versatile CYP109B1 enzyme from Bacillus subtilis has
      been solved at 1.8 A resolution. This is the first structure of an enzyme from
      this CYP family, whose members are prevalent across diverse species of bacteria.
      In the crystal structure the enzyme has an open conformation with an access
      channel leading from the heme to the surface. The substrate-free structure
      reveals the location of the key residues in the active site that are responsible
      for binding the substrate in the correct orientation for regioselective
      oxidation. Importantly, there are significant differences among these residues in
      members of the CYP109 and closely related CYP106 families and these likely
      account for the variations in substrate binding and oxidation profiles observed
      with these enzymes. A whole-cell oxidation biosystem was developed, which
      contains CYP109B1 and a phthalate family oxygenase reductase (PFOR), from
      Pseudomonas putida KT24440, as the electron transfer partner. This electron
      transfer system is able to support CYP109B1 activity resulting in the
      regioselective hydroxylation of both alpha- and beta-ionone in vivo and in vitro.
      The PFOR is therefore a versatile electron transfer partner that is able to
      support the activity of CYP enzymes from other bacterium. The crystal structure
      of CYP109B1 has a positively charged proximal face and this explains why it can
      interact with PFOR and adrenodoxin which are predominantly negatively charged
      around their [2Fe-2S] clusters. 

PMID- 25587702
TI  - Dermatologists, imiquimod, and treatment of molluscum contagiosum in children:
      righting wrongs.

PMID- 25587701
TI  - Effect of anular closure on disk height maintenance and reoperated recurrent
      herniation following lumbar diskectomy: two-year data.
AB  - OBJECTIVE: To assess the potential benefits of disk reherniation reduction and
      disk height maintenance in limited diskectomy combined with the implantation of
      the anular closure device. SUMMARY AND BACKGROUND DATA: Postoperative disk height
      loss is apparent in most patients undergoing lumbar diskectomy for herniated
      nucleus pulposus. Less favorable patient outcomes are associated with significant
      loss in disk height that can occur after aggressive disk tissue removal. More
      conservative disk removals, however, are often burdened by the increased risk of
      recurrent disk herniation. METHODS: Two prospective single-arm studies on
      patients treated with limited diskectomy and an anular closure device were
      conducted. Outcome measures included disk height maintenance relative to
      preoperative values, Oswestry Disability Index, back pain, leg pain, and
      complications such as reherniations. Patients were evaluated preoperatively and
      postoperatively at 6 weeks and at 3-, 6-, 12-, and 24-month time points. RESULTS:
      A total of 75 patients were included in this cohort consisting of 40 men and 35
      women with an average age of 40 years. Disk height maintenance within the group
      overall was 90% at 24 months. Overall, 97% of the treated disks demonstrated disk
      height maintenance of at least 75% of preoperative levels at 12 months and 92% at
      24 months. Disk height maintenance was correlated with less nucleus removal.
      Patient disability, back pain, and leg pain were significantly improved from
      preoperative levels at 6 weeks and maintained over the course of study. There was
      a single symptomatic reherniation requiring surgical intervention within this
      series. CONCLUSIONS: Limited lumbar diskectomy combined with the use of an anular
      closure device provided very low rates of disk reherniation and exhibited
      excellent disk height maintenance and sustained disability, leg pain, and back
      pain improvement within a 24-month postoperative study period. As with prior
      diskectomy studies, disk height maintenance was correlated with lower nucleus
      removal, although recurrence was less than in prior reports of limited
      diskectomy. Anular closure may allow for achievement of both objectives.

PMID- 25587703
TI  - Respiratory Tissue Engineering: Current Status and Opportunities for the Future.
AB  - Currently, lung disease and major airway trauma constitute a major global
      healthcare burden with limited treatment options. Airway diseases such as chronic
      obstructive pulmonary disease and cystic fibrosis have been identified as the
      fifth highest cause of mortality worldwide and are estimated to rise to fourth
      place by 2030. Alternate approaches and therapeutic modalities are urgently
      needed to improve clinical outcomes for chronic lung disease. This can be
      achieved through tissue engineering of the respiratory tract. Interest is growing
      in the use of airway tissue-engineered constructs as both a research tool, to
      further our understanding of airway pathology, validate new drugs, and pave the
      way for novel drug therapies, and also as regenerative medical devices or as an
      alternative to transplant tissue. This review provides a concise summary of the
      field of respiratory tissue engineering to date. An initial overview of airway
      anatomy and physiology is given, followed by a description of the stem cell
      populations and signaling processes involved in parenchymal healing and tissue
      repair. We then focus on the different biomaterials and tissue-engineered systems
      employed in upper and lower respiratory tract engineering and give a final
      perspective of the opportunities and challenges facing the field of respiratory
      tissue engineering. 

PMID- 25587704
TI  - Intracortical recording interfaces: current challenges to chronic recording
      function.
AB  - Brain Computer Interfaces (BCIs) offer significant hope to tetraplegic and
      paraplegic individuals. This technology relies on extracting and translating
      motor intent to facilitate control of a computer cursor or to enable fine control
      of an external assistive device such as a prosthetic limb. Intracortical
      recording interfaces (IRIs) are critical components of BCIs and consist of arrays
      of penetrating electrodes that are implanted into the motor cortex of the brain.
      These multielectrode arrays (MEAs) are responsible for recording and conducting
      neural signals from local ensembles of neurons in the motor cortex with the high
      speed and spatiotemporal resolution that is required for exercising control of
      external assistive prostheses. Recent design and technological innovations in the
      field have led to significant improvements in BCI function. However, long-term
      (chronic) BCI function is severely compromised by short-term (acute) IRI
      recording failure. In this review, we will discuss the design and function of
      current IRIs. We will also review a host of recent advances that contribute
      significantly to our overall understanding of the cellular and molecular events
      that lead to acute recording failure of these invasive implants. We will also
      present recent improvements to IRI design and provide insights into the
      futuristic design of more chronically functional IRIs.

PMID- 25587705
TI  - Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy.
AB  - Diabetic nephropathy often progresses to end-stage kidney disease and,
      ultimately, to renal replacement therapy. Hyperglycemia per se is expected to
      have a direct impact on the biosynthesis of N- and O-linked glycoproteins. This
      study aims to establish the link between protein glycosylation and progression of
      experimental diabetic kidney disease using orthogonal methods. Kidneys of
      streptozotocin-diabetic and control rats were harvested at three different time
      points post streptozotocin injection. A panel of 12 plant lectins was used in the
      screening of lectin blots. The lectins UEAI, PHA-E, GSI, PNA, and RCA identified
      remarkable disease-associated differences in glycoprotein expression. Lectin
      affinity chromatography followed by mass spectrometric analyses led to the
      identification of several glycoproteins involved in salt-handling, angiogenesis,
      and extracellular matrix degradation. Our data confirm a substantial link between
      glycosylation signature and diabetes progression. Furthermore, as suggested by
      our findings on dipeptidyl peptidase-IV, altered protein glycosylation may
      reflect changes in biochemical properties such as enzymatic activity. Thus, our
      study demonstrates the unexplored potential of protein glycosylation analysis in
      the discovery of molecules linked to diabetic kidney disease. 

PMID- 25587706
TI  - Fractalkine-CX3CR1-dependent recruitment and retention of human CD1c+ myeloid
      dendritic cells by in vitro-activated proximal tubular epithelial cells.
AB  - Chemokines play pivotal roles in tissue recruitment and retention of leukocytes,
      with CX3CR1 recently identified as a chemokine receptor that selectively targets
      mouse kidney dendritic cells (DCs). We have previously demonstrated increased
      tubulointerstitial recruitment of human transforming growth factor-beta (TGF
      beta)-producing DCs in renal fibrosis and chronic kidney disease (CKD). However,
      little is known about the mechanism of human DC recruitment and retention within
      the renal interstitium. We identified CD1c+ DCs as the predominant source of
      profibrotic TGF-beta and highest expressors of the fractalkine receptor CX3CR1
      within the renal DC compartment. Immunohistochemical analysis of diseased human
      kidney biopsies showed colocalization of CD1c+ DCs with fractalkine-positive
      proximal tubular epithelial cells (PTECs). Human primary PTEC activation with
      interferon-gamma and tumor necrosis factor-alpha induced both secreted and
      surface fractalkine expression. In line with this, we found fractalkine-dependent
      chemotaxis of CD1c+ DCs to supernatant from activated PTECs. Finally, in
      comparison with unactivated PTECs, we showed significantly increased adhesion of
      CD1c+ DCs to activated PTECs via a fractalkine-dependent mechanism. Thus, TGF
      beta-producing CD1c+ DCs are recruited and retained in the renal
      tubulointerstitium by PTEC-derived fractalkine. These cells are then positioned
      to play a role in the development of fibrosis and progression of chronic kidney
      disease.

PMID- 25587707
TI  - Alcohol consumption is inversely associated with the risk of developing chronic
      kidney disease.
AB  - There are few reports of associations between alcohol consumption and risk of
      chronic kidney disease (CKD). To investigate this further, we studied 5476
      participants aged 28-75 years in the Prevention of Renal and Vascular End-Stage
      Disease (PREVEND) study, a prospective population-based cohort, who were free of
      CKD at baseline (1997/1998). Alcohol consumption was self-reported on a
      questionnaire validated against serum high-density lipoprotein cholesterol. The
      primary outcome was de novo CKD defined as a combination of a creatinine-cystatin
      C-based estimated glomerular filtration rate (eGFR) under 60 ml/min per 1.73 m(2)
      and/or the mean of two consecutive 24-h urinary albumin excretions over 30 mg.
      During four serial follow-up examinations (median 10.2 years until February
      2012), 903 participants developed CKD. Compared with those abstaining from
      alcohol, the multivariable-adjusted hazard ratios (95% confidence interval) for
      CKD risk were 0.85 (0.69-1.04) for occasional (under 10 g/week), 0.82 (0.69-0.98)
      for light (10-69.9 g/week), 0.71 (0.58-0.88) for moderate (70-210 g/week), and
      0.60 (0.42-0.86) for heavier (over 210 g/week) alcohol consumers (significant
      trend). Similar inverse associations for alcohol consumption were found when CKD
      was defined as eGFR <60 ml/min per 1.73 m(2) or as 24-h urinary albumin excretion
      over 30 mg. Thus, in this population-based cohort, alcohol consumption was
      inversely associated with the risk of developing CKD. 

PMID- 25587708
TI  - Incidence and risk factors for new-onset atrial fibrillation among patients with
      end-stage renal disease undergoing renal replacement therapy.
AB  - Atrial fibrillation (AF) is prevalent in end-stage renal disease (ESRD) patients
      and negatively impacts patient outcomes. We explored the incidence and risk
      factors for new-onset AF among patients with ESRD undergoing renal replacement
      therapy, without a prior history of AF, retrieved from Taiwan's National Health
      Insurance Research Database (NHIRD). For each of 134,901 patients with ESRD, one
      age- and gender-matched control and one similarly matched patient with chronic
      kidney disease (CKD), a total of 404,703 patients, were selected from the NHIRD.
      The study endpoint was the occurrence of new-onset AF and patients were followed
      an average of 5.1 years. The incidence rates of AF were 12.1, 7.3, and 5.0 per
      1000 person-years for ESRD, CKD, and control patients, respectively. Among
      patients with ESRD, age, hypertension, heart failure, coronary artery disease,
      peripheral arterial occlusive disease, and chronic obstructive pulmonary disease
      were significant risk factors for new-onset AF. Thus, patients with ESRD had a
      significantly higher risk of new-onset AF. The presence of multiple risk factors
      was associated with a higher possibility of AF occurrence. 

PMID- 25587710
TI  - Organ donation after circulatory death in Switzerland: slow but constant
      progress.

PMID- 25587709
TI  - Renal developmental defects resulting from in utero hypoxia are associated with
      suppression of ureteric beta-catenin signaling.
AB  - Gestational stressors, including glucocorticoids and protein restriction, can
      affect kidney development and hence final nephron number. Since hypoxia is a
      common insult during pregnancy, we studied the influence of oxygen tension on
      kidney development in models designed to represent a pathological hypoxic insult.
      In vivo mouse models of moderate, transient, midgestational (12% O2, 48 h, 12.5
      dpc) or severe, acute, early-gestational (5.5-7.5% O2, 8 h, 9.5-10.5 dpc) hypoxia
      were developed. The embryo itself is known to mature under hypoxic conditions
      with embryonic tissue levels of oxygen estimated to be 5%-8% (physiological
      hypoxia) when the mother is exposed to ambient normoxia. Both in vivo models
      generated phenotypes seen in patients with congenital anomalies of the kidney and
      urinary tract (CAKUT). Severe, acute, early hypoxia resulted in duplex kidney,
      while moderate, transient, midgestational hypoxia permanently reduced ureteric
      branching and nephron formation. Both models displayed hypoxia-induced reductions
      in beta-catenin signaling within the ureteric tree and suppression of the
      downstream target gene, Ccnd1. Thus, we show a link between gestational hypoxia
      and CAKUT, the phenotype of which varies with timing, duration, and severity of
      the hypoxic insult.

PMID- 25587712
TI  - Plasmon resonance hybridization in self-assembled copper nanoparticle clusters:
      efficient and precise localization of surface plasmon resonance (LSPR) sensing
      based on Fano resonances.
AB  - In this work, we have investigated the hybridization of plasmon resonance modes
      in completely copper (Cu)-based subwavelength nanoparticle clusters from simple
      symmetric dimers to complex asymmetric self-assembled structures. The quality of
      apparent bonding and antibonding plasmon resonance modes for all of the clusters
      has been studied, and we examined the spectral response of each one of the
      proposed configurations numerically using the finite-difference time domain
      (FDTD) method. The effect of the geometric sizes of nanoparticles used and
      substrate refractive index on the cross-sectional profiles of each of the studied
      structures has been calculated and drawn. We proved that Fano-like resonance can
      be formed in Cu-based heptamer clusters as in analogous noble metallic particles
      (e.g., Au and Ag) by determining the coupling strength and interference between
      sub-radiant and super-radiant resonance modes. Employing certain Cu nanodiscs in
      designing an octamer structure, we measured the quality of the Fano dip formation
      along the scattering diagram. Accurate tuning of the geometric sizes for the Cu
      based octamer yields an opportunity to observe isotropic, deep, and narrow Fano
      minima along the scattering profile that are in comparable condition with the
      response of other plasmonic metallic substances. Immersing investigated final Cu
      based octamer in various liquids with different refractive indices, we determined
      the sensing accuracy of the cluster based on the performance of the Fano dip.
      Plotting a linear diagram of plasmon energy differences over the refractive index
      variations as a figure of merit (FoM), which we have quantified as 13.25. With
      this method, the precision of the completely Cu-based octamer is verified
      numerically using the FDTD tool. This study paves the way toward the use of Cu as
      an efficient, low-cost, and complementary metal-oxide semiconductor (CMOS)
      compatible plasmonic material with optical properties that are similar to
      analogous plasmonic substances. 

PMID- 25587713
TI  - Synthesis of a red fluorescent dye-conjugated Ag@SiO2 nanocomposite for cell
      immunofluorescence.
AB  - In this work we describe a one-step approach for incorporating a red fluorophore
      (2SBPO) into core-shell nanoparticles for metal-enhanced fluorescence
      immunolabels. The 2SBPO-MEF nanoparticles are particularly attractive as cell
      labels because their ~ 670 nm emission has minimal overlap with cell
      autofluorescence and from overlap with many conventional probes. 2SBPO was
      incorporated through physical entrapment during the Stober process. Antibody
      based cell labels were then synthesized using covalent linkage. The nanoparticle
      fluorescence was 7.5-fold higher than control nanoparticles lacking a metal core.
      We demonstrated labeling of CD4 + HuT 78 T lymphocytes using anti-CD4-conjugated
      nanoparticle labels. Cells labeled with anti-CD4 nanoparticles showed a 35-fold
      fluorescence signal compared to anti-CD4 coreless controls. This simple synthesis
      protocol can be applied to a variety of hydrophilic fluorophore types and has
      broad potential in bioanalytical and biosensing applications. 

PMID- 25587711
TI  - Female streetwalkers' perspectives on migration and HIV/STI risks in a changing
      economic and social environment: a qualitative study in Shanghai, China.
AB  - China's 30-year economic boom has created a unique social and economic market for
      commercial sex, as well as for a workforce of migrant women from rural China.
      This qualitative study explores the impact of the rapidly changing social and
      economic environment on migration patterns, knowledge of sexually transmitted
      infections (STIs), STI risk behaviours and health beliefs among female
      streetwalkers in Shanghai. Qualitative data were collected in 2010 through semi
      structured in-depth interviews with 16 streetwalkers to characterise their
      migration passages, sexual health and behaviours, and peer networks. Many
      streetwalkers reported histories of childhood impoverishment, of family or
      partner violence or trauma, of migration consistent with the timeline and routes
      of economic development and of a scarcity in health, social or economic support.
      Their knowledge of the prevention and treatment of HIV and STIs was limited. They
      had little bargaining power on condom use and the majority resorted to vaginal
      douching and self-management with antibiotics as preventative measures. The study
      identifies streetwalkers' perspectives on the changing environment, their options
      and actions and, finally, HIV/STI risks that were unique to this hidden
      population. 

PMID- 25587714
TI  - The importance of research in undergraduate medical education.
AB  - Currently medical information flows at great speed, bombarding medical students.
      Students are unfamiliar with fundamental aspects of biomedical literature
      appraisal. We assert that research performed during medical school will help to
      reduce the gap between the information available and comprehension by the
      student. The goal of the present review is to expound the importance of
      performing research during the undergraduate medical years and the relevance of
      research in other fields of medicine. We performed a literature review searching
      MEDLINE with terms consistent with our objective. We discuss the conduct of
      research projects during medical school training. The analysis of the articles
      retrieved proves that research is feasible and that it is a critical process
      during the undergraduate period for medical students. 

PMID- 25587715
TI  - Relationships between the Osteocalcin gene polymorphisms, serum osteocalcin
      levels, and hepatitis B virus-related hepatocellular carcinoma in a Chinese
      population.
AB  - BACKGROUND: Available evidence has demonstrated that osteocalcin may play a role
      in pathogenesis of cancer, and mutation of the osteocalcin gene may be involved
      in the cancer development. The aim of this study is to determine whether
      osteocalcin gene polymorphisms are associated with hepatitis B virus (HBV)
      related hepatocellular carcinoma (HCC) among Chinese population. METHODS: A total
      of 515 subjects were divided into four groups: 129 patients with chronic
      hepatitis B (CHB), 62 patients with HBV-related liver cirrhosis (LC), 154
      patients with HBV-related HCC, and 170 healthy controls. The polymerase chain
      reaction-restriction fragment length polymorphism strategy was used to detect
      osteocalcin gene rs1800247 and rs1543297 polymorphisms. RESULTS: Compared with
      healthy controls, the rs1800247 HH and Hh genotypes were associated with a
      significantly increased susceptibility to HCC (HH versus hh: OR = 6.828, 95% CI
      2.620-17.795, P < 0.001; Hh versus hh: OR = 6.306, 95% CI 3.480-11.423, P <
      0.001, respectively). Similarly, the subjects bearing the H allele of rs1800247
      had more than a 2.4-fold increased risk for development of HCC (OR = 2.484, 95%
      CI 1.747-3.532, P < 0.001) compared with those bearing the h allele. In addition,
      we found significant decreased serum osteocalcin levels in HBV-related HCC
      patients (11.73 +/- 8.18 ng/mL) compared with healthy controls (15.3 +/- 6.06
      ng/mL). Furthermore, the serum osteocalcin levels were significantly lower in HCC
      patients than healthy controls among the individuals with heterozygous Hh
      genotype (P = 0.003) and CT genotype (P < 0.001). In contrast, there were no
      significant differences in the genotype and allele of rs1543297 polymorphisms
      between the groups of patients and healthy controls. CONCLUSIONS: These findings
      for the first time suggest that genetic variant in osteocalcin gene rs1800247
      polymorphisms may be a risk factor for HBV-related HCC. We also find an inverse
      association of serum osteocalcin levels with HCC.

PMID- 25587716
TI  - Plasmid-mediated AmpC: prevalence in community-acquired isolates in Amsterdam,
      the Netherlands, and risk factors for carriage.
AB  - OBJECTIVES: The objective of this study was to determine the prevalence of pAmpC
      beta-lactamases in community-acquired Gram negative bacteria in the Netherlands,
      and to identify possible risk factors for carriage of these strains. METHODS:
      Fecal samples were obtained from community-dwelling volunteers. Participants also
      returned a questionnaire for analysis of risk factors. Screening for pAmpC was
      performed with selective enrichment broth and a selective screening agar.
      Confirmation of AmpC-production was performed with two double disc combination
      tests: cefotaxime and ceftazidime with either boronic acid or cloxacillin as
      inhibitor. Multiplex PCR was used as gold standard for detection of pAmpC. 16S
      rRNA PCR and AFLP were performed as required, plasmids were identified by PCR
      based replicon typing. Questionnaire results were analyzed with SPSS, version
      20.0. RESULTS: Fecal samples were obtained from 550 volunteers; mean age 51 years
      (range: 18-91), 61% were females. pAmpC was present in seven E. coli isolates
      (7/550, 1.3%, 0.6-2.7 95% CI): six CMY-2-like pAmpC and one DHA. ESBL-encoding
      genes were found in 52/550 (9.5%, 7.3-12.2 95% CI) isolates; these were
      predominantly blaCTX-M genes. Two isolates had both ESBL and pAmpC. Admission to
      a hospital in the previous year was the only risk factor we identified.
      CONCLUSIONS: Our data indicate that the prevalence of pAmpC in the community
      seems still low. However, since pAmpC-producing isolates were not identified as
      ESBL producers by routine algorithms, there is consistent risk that further
      increase of their prevalence might go undetected.

PMID- 25587717
TI  - MiR-21 enhances melanoma invasiveness via inhibition of tissue inhibitor of
      metalloproteinases 3 expression: in vivo effects of MiR-21 inhibitor.
AB  - Metastatic melanoma is the most aggressive form of this cancer. It is important
      to understand factors that increase or decrease metastatic activity in order to
      more effectively research and implement treatments for melanoma. Increased cell
      invasion through the extracellular matrix is required for metastasis and is
      enhanced by matrix metalloproteinases (MMPs). Tissue inhibitor of
      metalloproteinases 3 (TIMP3) inhibits MMP activity. It was previously shown by
      our group that miR-21, a potential regulator of TIMP3, is over-expressed in
      cutaneous melanoma. It was therefore hypothesized that increased levels of miR-21
      expression would lead to decreased expression of TIMP3 and thereby enhance the
      invasiveness of melanoma cells. miR-21 over-expression in the melanoma cell lines
      WM1552c, WM793b, A375 and MEL 39 was accomplished via transfection with pre-miR
      21. Immunoblot analysis of miR-21-overexpressing cell lines revealed reduced
      expression of TIMP3 as compared to controls. This in turn led to a significant
      increase in the invasiveness of the radial growth phase cell line WM1552c and the
      vertical growth phase cell line WM793b (p < 0.05), but not in the metastatic cell
      lines A375 or MEL 39. The proliferation and migration of miR-21 over-expressing
      cell lines was not affected. Reduced expression of TIMP3 was achieved by siRNA
      knockdown and significantly enhanced invasion of melanoma cell lines, mimicking
      the effects of miR-21 over-expression. Treatment of tumor cells with a linked
      nucleic acid antagomir to miR-21 inhibited tumor growth and increased tumor
      expression of TIMP3 in vivo in 01B74 Athymic NCr-nu/nu mice. Intra-tumoral
      injections of anti-miR-21 produced similar effects. This data shows that
      increased expression of miR-21 enhanced the invasive potential of melanoma cell
      lines through TIMP3 inhibition. Therefore, inhibition of miR-21 in melanoma may
      reduce melanoma invasiveness. 

PMID- 25587718
TI  - Modeling nociception in zebrafish: a way forward for unbiased analgesic
      discovery.
AB  - Acute and chronic pain conditions are often debilitating, inflicting severe
      physiological, emotional and economic costs and affect a large percentage of the
      global population. However, the development of therapeutic analgesic agents based
      primarily on targeted drug development has been largely ineffective. An
      alternative approach to analgesic development would be to develop low cost, high
      throughput, untargeted animal based behavioral screens that model complex
      nociceptive behaviors in which to screen for analgesic compounds. Here we
      describe the development of a behavioral based assay in zebrafish larvae that is
      effective in identifying small molecule compounds with analgesic properties. In a
      place aversion assay, which likely utilizes supraspinal neuronal circuitry,
      individually arrayed zebrafish larvae show temperature-dependent aversion to
      increasing and decreasing temperatures deviating from rearing temperature.
      Modeling thermal hyperalgesia, the addition of the noxious inflammatory compound
      and TRPA1 agonist allyl isothiocyanate sensitized heat aversion and reversed cool
      aversion leading larvae to avoid rearing temperature in favor of otherwise
      acutely aversive cooler temperatures. We show that small molecules with known
      analgesic properties are able to inhibit acute and/or sensitized temperature
      aversion. 

PMID- 25587720
TI  - Perchlorate in indoor dust and human urine in China: contribution of indoor dust
      to total daily intake.
AB  - Perchlorate is used in fireworks and China is the largest fireworks producer and
      consumer in the world. Information regarding human exposure to perchlorate is
      scarce in China, and exposure via indoor dust ingestion (EDI indoor dust) has
      rarely been evaluated. In this study, perchlorate was found in indoor dust
      (detection rate: 100%, median: 47.4 MUg/g), human urine (99%, 26.2 ng/mL),
      drinking water (100%, 3.99 ng/mL), and dairy milk (100%, 12.3 ng/mL) collected
      from cities that have fireworks manufacturing areas (Yueyang and Nanchang) and in
      cities that do not have fireworks manufacturing industries (Tianjin,
      Shijiazhuang, Yuxi and Guilin) in China. In comparison with perchlorate levels
      reported for other countries, perchlorate levels in urine samples from fireworks
      sites and nonfireworks sites in China were higher. Median indoor dust perchlorate
      concentrations were positively correlated (r = 0.964, p < 0.001) with outdoor
      dust perchlorate levels reported previously. The total daily intake (EDI total)
      of perchlorate, estimated based on urinary levels, ranged from 0.090 to 27.72
      MUg/kg body weight (bw)/day for all studied participants; the percentage of
      donors who had EDI total exceeding the reference dose (RfD) recommended by the
      United States Environmental Protection Agency (US EPA) was 79%, 48%, and 25% for
      toddlers (median: 1.829 MUg/kg bw/day), adults (0.669 MUg/kg bw/day), and
      children (median: 0.373 MUg/kg bw/day), respectively. Toddlers (0.258 MUg/kg
      bw/day) had the highest median EDI indoor dust, which was 2 to 5 times greater
      than the EDI indoor dust calculated for other age groups (the range of median
      values: 0.044 to 0.127 MUg/kg bw/day). Contribution of indoor dust to EDItotal
      was 26%, 28%, and 7% for toddlers, children, and adults, respectively. Indoor
      dust contributed higher percentage to EDI total than that by dairy milk (0.5-5%).

PMID- 25587721
TI  - Association between pornography use and sexual risk behaviors in adult consumers:
      a systematic review.
AB  - The purpose of this review was to determine whether an association exists between
      sexual risk behaviors and pornography consumption. Consumption of pornography is
      common, yet research examining its link with sexual risk behaviors is in its
      infancy. Indicators of sexual risk behavior, including unsafe sex practices and a
      higher number of sexual partners, have been linked to poor health outcomes. A
      systematic literature search was performed using Medline, PsycINFO, Web of
      Knowledge, Pubmed, and CINAHL. Studies were included if they assessed the
      association between pornography use and indicators of sexual risk behaviors in an
      adult population. A total of 17 were included in the review, and all were
      assessed for research standards using the Quality Index Scale. For both Internet
      pornography and general pornography, links with greater unsafe sex practices and
      number of sexual partners were identified. Limitations of the literature,
      including low external validity and poor study design, restrict the
      generalizability of the findings. Accordingly, replication and more rigorous
      methods are recommended for future research. 

PMID- 25587723
TI  - AVMA issues guidance on humane slaughter.
AB  - First-of-its-kind document addresses each stage of slaughter process.

PMID- 25587724
TI  - Potential confounding factors in cancer studies.

PMID- 25587726
TI  - What is your diagnosis? Pulmonary osteoma.

PMID- 25587725
TI  - Antimicrobial stewardship in companion animal practice.

PMID- 25587727
TI  - What is your diagnosis? Biliary tract obstruction.

PMID- 25587728
TI  - Diagnostic imaging in veterinary dental practice. Persistent deciduous teeth.

PMID- 25587729
TI  - Pathology in practice. Mediastinal thyroid follicular carcinoma and adrenal
      carcinoma.

PMID- 25587719
TI  - The pathogenic role of persistent milk signaling in mTORC1- and milk-microRNA
      driven type 2 diabetes mellitus.
AB  - Milk, the secretory product of the lactation genome, promotes growth of the
      newborn mammal. Milk delivers insulinotropic amino acids, thus maintains a
      molecular crosstalk with the pancreatic beta-cell of the milk recipient.
      Homeostasis of beta-cells and insulin production depend on the appropriate
      magnitude of mTORC1 signaling. mTORC1 is activated by branched-chain amino acids
      (BCAAs), glutamine, and palmitic acid, abundant nutrient signals of cow's milk.
      Furthermore, milk delivers bioactive exosomal microRNAs. After milk consumption,
      bovine microRNA-29b, a member of the diabetogenic microRNA-29- family, reaches
      the systemic circulation and the cells of the milk consumer. MicroRNA-29b
      downregulates branchedchain alpha-ketoacid dehydrogenase, a potential explanation
      for increased BCAA serum levels, the metabolic signature of insulin resistance
      and type 2 diabetes mellitus (T2DM). In non-obese diabetic mice, microRNA-29b
      downregulates the antiapoptotic protein Mcl-1, which leads to early beta-cell
      death. In all mammals except Neolithic humans, milk-driven mTORC1 signaling is
      physiologically restricted to the postnatal period. In contrast, chronic
      hyperactivated mTORC1 signaling has been associated with the development of age
      related diseases of civilization including T2DM. Notably, chronic hyperactivation
      of mTORC1 enhances endoplasmic reticulum stress that promotes apoptosis. In fact,
      hyperactivated beta-cell mTORC1 signaling induced early beta-cell apoptosis in a
      mouse model. The EPIC-InterAct Study demonstrated an association between milk
      consumption and T2DM in France, Italy, United Kingdom, Germany, and Sweden. In
      contrast, fermented milk products and cheese exhibit an inverse correlation.
      Since the early 1950's, refrigeration technology allowed widespread consumption
      of fresh pasteurized milk, which facilitates daily intake of bioactive bovine
      microRNAs. Persistent uptake of cow's milk-derived microRNAs apparently transfers
      an overlooked epigenetic diabetogenic program that should not reach the human
      food chain. 

PMID- 25587730
TI  - Formulation and validation of a predictive model to correct blood glucose
      concentrations obtained with a veterinary point-of-care glucometer in hemodiluted
      and hemoconcentrated canine blood samples.
AB  - OBJECTIVE: To determine the effect of PCV on veterinary point-of-care (POC)
      glucometer measurements in canine blood samples and develop a formula to correct
      the glucose concentration as measured by a point-of-care glucometer (POCgluc)
      given a known PCV. DESIGN: Experimental and prospective study. SAMPLES: Blood
      samples from 6 healthy dogs and from 30 hospitalized dogs. PROCEDURES: 60 mL of
      heparinized blood was obtained from each of 6 healthy dogs. Samples were
      processed into packed RBCs and plasma. Packed RBCs were resuspended with plasma
      to achieve a range of PCVs from 0% to 94%. Duplicate POCgluc and PCV measurements
      were obtained for each dilution; following POCgluc measurements, plasma samples
      were analyzed for glucose concentration by a clinical laboratory biochemical
      analyzer (LABgluc). A correction formula for POCgluc was developed. Measurements
      of POCgluc, PCV, and LABgluc were also determined from blood samples of 30 dogs
      admitted to the veterinary teaching hospital. RESULTS: Values of LABgluc for each
      sample were similar at any PCV. As PCV decreased, POCgluc was falsely increased;
      as PCV increased, POCgluc was falsely decreased, compared with LABgluc. The
      absolute difference between POCgluc and LABgluc increased as the PCV changed from
      50%. Compared with POCgluc, the corrected POCgluc had a significantly improved
      correlation with LABgluc, which was also reflected in improvements in Clarke and
      consensus error grid analyses. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated that in dogs with hemodilution or hemoconcentration, POCgluc did not
      reflect actual patient glucose concentrations. Use of a correction formula
      reduced this error. Corrected POCgluc data had strong, significant correlations
      with LABgluc data.

PMID- 25587731
TI  - Diagnostic quality of percutaneous fine-needle aspirates and laparoscopic biopsy
      specimens of the liver in rabbits (Oryctolagus cuniculus).
AB  - OBJECTIVE: To evaluate diagnostic quality of liver percutaneous ultrasound-guided
      fine-needle aspirates and laparoscopic biopsy specimens of rabbits (Oryctolagus
      cuniculus). DESIGN: Prospective descriptive study. ANIMALS: 7 healthy adult
      rabbits. PROCEDURES: 3 to 5 liver fine-needle aspirates were obtained with a 22
      gauge needle under ultrasound guidance in anesthetized rabbits. Liver biopsy
      specimens were also obtained with 1.7-mm (n = 2) or 3.0-mm (1) biopsy forceps by
      direct laparoscopic observation. Fine-needle aspirates were cytologically
      evaluated on a scale from 0 (suboptimal specimen) to 3 (optimal specimen) for
      cellularity, cell distribution, cell preservation, cell morphology, and blood
      contamination. Biopsy specimens were histologically evaluated on a scale from 0
      (optimal specimen) to 5 (suboptimal specimen) for artifactual changes; numbers of
      portal triads and central veins were quantified. RESULTS: Aspirates were
      moderately to highly cellular (mean, 2.54) with good cell distribution (mean,
      2.56), good cell preservation (mean, 2.20), and moderate blood contamination
      (mean, 1.04). The 1.7-mm biopsy specimens had a mean score of 1.3 for artifactual
      changes and contained a mean of 0.6 portal triads and 1.6 central veins/biopsy
      specimen. The 3.0-mm liver biopsy specimens had a mean score of 2.7 for
      artifactual changes, with a mean of 4.0 portal triads and 4.14 central
      veins/biopsy specimen. All but one 3.0-mm liver biopsy specimen had >= 1 portal
      triad suitable for histologic evaluation, and all had >= 1 central vein; in
      contrast, only half of the 1.7-mm liver biopsy specimens had a discernible portal
      triad or central vein. CONCLUSIONS AND CLINICAL RELEVANCE: For histologic
      evaluation, advantages of obtaining 3.0-mm liver biopsy specimens, compared with
      1.7-mm liver biopsy specimens or fine-needle aspirates, should be considered in
      rabbits with suspected liver disease.

PMID- 25587732
TI  - Internal obturator muscle transposition for treatment of perineal hernia in dogs:
      34 cases (1998-2012).
AB  - OBJECTIVE: To evaluate the outcome of dogs with perineal hernia treated with
      transposition of the internal obturator muscle. DESIGN: Retrospective case
      series. ANIMALS: 34 dogs. PROCEDURES: Medical records of dogs with perineal
      hernia surgically treated from 1998 to 2012 were reviewed. Diagnostic methods and
      surgical techniques were recorded. Dogs were assigned preoperative and
      postoperative clinical sign scores. Complication and recurrence rates were
      evaluated over time. Risk factors were determined. RESULTS: Median follow-up time
      was 345 days (range, 22 to 1,423 days). Complications were observed in 10 dogs.
      Tenesmus (n = 9), dyschezia (7), fecal impaction (3), stranguria (4),
      hematochezia (2), urinary incontinence (2), diarrhea (1), urinary tract infection
      (1), and megacolon (1) occurred following surgery. Bladder retroflexion at the
      time of initial evaluation or surgery was not a risk factor for complication
      (hazard ratio, 1.72). One year after surgery, 51.2% dogs were free of
      complications. Three dogs developed a perineal hernia on the contralateral side
      between 35 and 95 days after surgery. The 1-year recurrence rate was 27.4%.
      Median time for recurrence was 28 days after surgery (range, 2 to 364 days).
      Postoperative tenesmus was a risk factor for the development of recurrence
      (hazard ratio, 2.29). CONCLUSIONS AND CLINICAL RELEVANCE: Internal obturator
      muscle transposition was used for primary repair of perineal hernia in dogs.
      Recurrence was recorded as long as 1 year after surgery. Tenesmus was a risk
      factor for the development of recurrence after treatment of perineal hernia with
      internal obturator muscle transposition.

PMID- 25587733
TI  - Incidence of and risk factors for postoperative regurgitation and vomiting in
      dogs: 244 cases (2000-2012).
AB  - OBJECTIVE: To determine the incidence of and risk factors for postoperative
      regurgitation and vomiting (PORV) in dogs. DESIGN: Retrospective cohort study.
      ANIMALS: 244 client-owned dogs. PROCEDURES: Dogs referred for nonelective surgery
      in the first 3 months of 2000 and 2012 were included. Breed; sex; age; weight;
      body condition score; emergency status; food withholding status; history of
      vomiting or regurgitation; American Society of Anesthesiologists score; presence
      of diabetes or hypothyroidism; preoperative PCV and total solids concentration;
      anesthesia protocol; corticosteroid, opioid, neuromuscular blocking agent, and
      nitrous oxide usage; anesthesia time; surgery time; type of surgery; and
      occurrence of vomiting or regurgitation within 24 hours after recovery from
      anesthesia were recorded. Data were analyzed by means of the Fisher exact test,
      Wilcoxon rank sum test, and logistic regression. RESULTS: 30 of 244 (12.3%) dogs
      meeting study inclusion criteria developed PORV. There was no significant
      difference in the incidence of PORV between the 2000 (12/111 [10.8%]) and 2012
      (18/133 [13.5%]) cohorts, although the incidence of regurgitation was higher in
      2012. Univariate logistic regression identified the most significant risk factors
      as gastrointestinal surgery (OR, 11.15; 95% confidence interval [CI], 3.11 to
      40.03), premedication without strong sedatives including either an alpha2
      adrenoceptor agonist or acepromazine (OR, 5.36; 95% CI, 1.89 to 15.17), American
      Society of Anesthesiologists score of 4 (OR, 5.25; 95% CI, 1.05 to 26.15),
      history of vomiting or regurgitation (OR, 5.12; 95% CI, 1.83 to 14.31), emergency
      surgery (OR, 4.08; 95% CI, 1.29 to 12.90), neurologic surgery (OR, 3.18; 95% CI,
      1.02 to 9.92), sevoflurane inhalation anesthesia (OR, 2.78; 95% CI, 1.25 to
      6.13), and being sexually intact (OR, 2.37; 95% CI, 1.07 to 5.27). Multivariate
      analysis was not clinically useful owing to the low sensitivity and specificity
      of the model. CONCLUSIONS AND CLINICAL RELEVANCE: Between 2000 and 2012, there
      was no change in the incidence of PORV for dogs undergoing neurologic,
      orthopedic, and soft tissue surgical procedures; however, the proportion of dogs
      that regurgitated increased significantly in 2012. Preoperative antiemetic
      prophylaxis should be considered in dogs undergoing gastrointestinal surgery and
      in those in which other risk factors are present.

PMID- 25587734
TI  - Computed tomographic features of clinical and subclinical middle ear disease in
      domestic rabbits (Oryctolagus cuniculus): 88 cases (2007-2014).
AB  - OBJECTIVE: To describe and compare CT abnormalities of the middle ear in rabbits
      (Oryctolagus cuniculus) that had clinical or subclinical middle ear disease and
      to determine the prevalence of otitis media and evaluate the role of predisposing
      factors for otitis media in that species. DESIGN: Retrospective case series.
      ANIMALS: 88 domestic rabbits. PROCEDURES: Medical records for rabbits that
      underwent CT of the head in June 2007 through February 2014 were searched and
      classified on the basis of reason for head CT (i.e., ear-related disease vs non
      ear-related disease). The ears, upper respiratory tract, teeth, and other
      important structures of each rabbit's head were evaluated. Follow-up information
      was obtained for rabbits with CT abnormalities of the middle ear without clinical
      signs (i.e., subclinical disease). RESULTS: 12 of 21 (57%) rabbits with clinical
      signs of ear disease and 18 of 67 (27%) rabbits without clinical signs of ear
      disease had CT abnormalities of the middle ear. In CT images, all affected ears
      had soft tissue-attenuating material within the tympanic bulla. Tympanic bulla
      lysis was associated with clinical middle ear disease. Most (12/18) rabbits with
      subclinical middle ear disease remained subclinical after CT examination. Middle
      ear CT-detected changes and lop-ear conformation or otitis externa were strongly
      correlated; middle ear disease and upper respiratory tract disease were not
      correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggested that subclinical
      otitis media frequently affects rabbits, and those with bulla lysis should be
      closely monitored. Lop-eared rabbits and rabbits with otitis externa had a higher
      risk of developing otitis media.

PMID- 25587735
TI  - Extensive placental choriovascular infiltration by maturing myeloid cells in down
      syndrome-associated transient abnormal myelopoiesis.
AB  - Transient abnormal myelopoiesis (TAM), a clonal proliferation of predominantly
      megakaryocytic precursor cells, affects 4%-10% of newborns with Down syndrome.
      Approximately 20%-30% of TAM survivors are at risk of development of acute
      myeloid leukemia (myeloid leukemia associated with Down syndrome, ML-DS). We
      report unusual placental findings in a female infant with trisomy 21 born at 38
      weeks of gestation. In line with previous descriptions of placental pathology in
      infants with TAM, abundant blast-like cells were present in the lumen of
      chorionic and stem villous vessels. In addition, there was multifocal extensive
      infiltration of the wall of chorionic vessels by maturing myeloid cells in a
      pattern reminiscent of TAM- or leukemia-associated systemic infiltration. The
      clinical significance of this unusual choriovascular involvement of the placenta
      in TAM is undetermined. 

PMID- 25587736
TI  - Commentary on "A dietary restriction influences the progression but not the
      initiation of MSG-induced nonalcoholic steatohepatitis".

PMID- 25587737
TI  - Effects of several temporomandibular disorders on the stress distributions of
      temporomandibular joint: a finite element analysis.
AB  - The aim of this study was to evaluate stress distributions in the
      temporomandibular joints (TMJs) with temporomandibular disorders (TMDs) for
      comparison with healthy TMJs. A model of mandible and normal TMJs was developed
      according to CT images. The interfaces between the discs and the articular
      cartilages were treated as contact elements. Nonlinear cable elements were used
      to simulate disc attachments. Based on this model, seven models of various TMDs
      were established. The maximum stresses of the discs with anterior, posterior,
      medial and lateral disc displacement (ADD, PDD, MDD and LDD) were 12.09, 9.33,
      10.71 and 6.07 times magnitude of the identically normal disc, respectively. The
      maximum stresses of the posterior articular eminences in ADD, PDD, MDD, LDD,
      relaxation of posterior attachments and disc perforation models were 21, 59, 46,
      21, 13 and 15 times greater than the normal model, respectively. TMDs could cause
      increased stresses in the discs and posterior articular eminences. 

PMID- 25587738
TI  - Molecular design of boronic acid-functionalized squarylium cyanine dyes for
      multiple discriminant analysis of sialic acid in biological samples: selectivity
      toward monosaccharides controlled by different alkyl side chain lengths.
AB  - We designed a new series of boronic acid-functionalized squarylium cyanine dyes
      (SQ-BA) with different lengths of alkyl chain residues, suitable for multiple
      discriminant analysis (MDA) of sialic acid (Neu5Ac) in biological samples. The SQ
      BA dyes form aggregates based on hydrophobic interactions, which result in
      quenched fluorescence in aqueous solutions. When the boronic acid binds with
      saccharides, the fluorescence intensity increases as a result of dissociation to
      the emissive monomeric complex. We inferred that different dye aggregate
      structures (H-aggregates and J-aggregates) were induced depending on the alkyl
      chain length, so that monosaccharides would be recognized in different ways
      (especially, multipoint interaction with J-aggregates). A distinctive emission
      enhancement of SQ-BA dyes with shorter-alkyl-chains in the presence of Neu5Ac was
      observed (2.4-fold fluorescence enhancement; with formation constant 10(1.7) M(
      1)), with no such enhancement for SQ-BA dyes with longer-alkyl-chain. In
      addition, various enhancement factors for other monosaccharides were observed
      depending on the alkyl chain length. Detailed thermodynamic and NMR studies of
      the SQ-BA complexes revealed the unique recognition mechanism: the dye aggregate
      with a shorter-alkyl-chain causes the slipped parallel structure and forms a
      stable 2:1 complex with Neu5Ac, as distinct from longer-alkyl-chain dyes, which
      form a 1:1 monomeric complex. MDA using the four SQ-BA dyes was performed for
      human urine samples, resulting in the successful discrimination between normal
      and abnormal Neu5Ac levels characteristic of disease. Thus, we successfully
      controlled various responses to similar monosaccharides with a novel approach
      that chemically modified not the boronic acid moiety itself but the length of the
      alkyl chain residue attached to the dye in order to generate specificity. 

PMID- 25587739
TI  - Antigiardial activity of glycoproteins and glycopeptides from Ziziphus honey.
AB  - Natural honey contains an array of glycoproteins, proteoglycans and
      glycopeptides. Size-exclusion chromatography fractionated Ziziphus honey proteins
      into five peaks with molecular masses in the range from 10 to >200 kDa. The
      fractionated proteins exhibited in vitro activities against Giardia lamblia with
      IC50 values <= 25 MUg/mL. Results indicated that honey proteins were more active
      as antiprotozoal agents than metronidazole. This study indicated the potential of
      honey proteins and peptides as novel antigiardial agents.

PMID- 25587740
TI  - Impact of therapeutic irradiation on healthy articular cartilage.
AB  - Radiation-induced complications in bone and cartilage are of increasing concern
      due to potential long-term effects in cancer survivors. Healthy articular
      cartilage may be exposed to radiation during either chondrosarcoma treatment or
      in-field radiotherapy of tumors located in close proximity to articulation.
      Cartilage exposed to radiation undergoes bone differentiation and senescence,
      which can lead to painful and disabling sequelae that can impair patient quality
      of life. An understanding of the biological processes involved in healthy
      cartilage response to radiotherapy may not only optimize the delivery of
      therapeutic radiation but also reduce the risk of long-term sequelae in
      irradiated cartilage. Over the last few decades, radiobiology studies have
      focused primarily on signaling and repair of DNA damage pathways induced by
      ionizing radiation in immortalized cells under conditions dramatically different
      from human homeostasis. This research needs to be continued and broadened, since
      the range of normal tissue responses to radiation exposure is still not fully
      understood, despite being recognized as the major limiting factor in the rupture
      of tissue homeostasis after radiotherapy. Human articular cartilage is an
      avascular tissue with low intracellular oxygen levels and is comprised of a
      single cell lineage of chondrocytes embedded in a highly dense and structured
      extracellular matrix. These relatively unique features may impact inherent cell
      radiation sensitivity and suggests that canonical cell responses to ionizing
      radiation may not be applicable to articular cartilage. Despite the number of
      studies in this field, radiation-induced modifications of chondrocyte proteome
      remain unclear because of the dramatic variability in reported experimental
      conditions. In this review, we propose to introduce cartilage tissue physiology
      and microenvironment concepts, and then present a comprehensive synthesis of
      cartilage radiation biology. 

PMID- 25587741
TI  - Radiobiological intercomparison of the 160 MeV and 230 MeV proton therapy beams
      at the Harvard Cyclotron Laboratory and at Massachusetts General Hospital.
AB  - The purpose of this study was to determine the relative biological effectiveness
      (RBE) along the axis of two range-modulated proton beams (160 and 230 MeV). Both
      the depth and the dose dependence of RBE were investigated. Chinese hamster V79
      WNRE cells, suspended in medium containing gelatin and cooled to 2  degrees C,
      were used to obtain complete survival curves at multiple positions throughout the
      entrance and 10 cm spread-out Bragg peak (SOBP). Simultaneous measurements of the
      survival response to (60)Co gamma rays served as the reference data for the
      proton RBE determinations. For both beams the RBE increased significantly with
      depth in the 10 cm SOBP, particularly in the distal half of the SOBP, then rose
      even more sharply at the distal edge, the most distal position measured. At a 4
      Gy dose of gamma radiation (S = 0.34) the average RBE values for the entrance,
      proximal half, distal half and distal edge were 1.07 +/- 0.01, 1.10 +/- 0.01,
      1.17 +/- 0.01 and 1.21 +/- 0.01, respectively, and essentially the same for both
      beams. At a 2 Gy dose of gamma radiation (S = 0.71) the average RBE values rose
      to 1.13 +/- 0.03, 1.15 +/- 0.02, 1.26 +/- 0.02 and 1.30 +/- 0.02, respectively,
      for the same four regions of the SOBP. The difference between the 4 Gy and 2 Gy
      RBE values reflects the dose dependence of RBE as measured in these V79-WNRE
      cells, which have a low alpha/beta value, as do other widely used cell lines that
      also show dose-dependent RBE values. Late-responding tissues are also
      characterized by low alpha/beta values, so it is possible that these cell lines
      may be predictive for the response of such tissues (e.g., spinal cord, optic
      nerve, kidney, liver, lung). However, in the very small number of studies of late
      responding tissues performed to date there appears to be no evidence of an
      increased RBE for protons at low doses. Similarly, RBE measurements using early
      responding in vivo systems (mostly mouse jejunum, an early-responding tissue
      which has a large alpha/beta ~ 10 Gy) have generally shown little or no
      detectable dose dependence. It is useful to compare the RBE values reported here
      to the commonly used generic clinical RBE of 1.1, which assumes no dependence on
      depth or on dose. Our proximal RBEs obviously avoid the depth-related increase in
      RBE and for doses of 4 Gy or more, the low-dose increase in RBE is also
      minimized, as shown in this article. Thus the proximal RBE at a 4 Gy dose of 1.10
      +/- 0.01, quoted above, represents an interesting point of congruence with the
      clinical RBE for conditions where it could reasonably be expected in the
      measurements reported here. The depth dependence of RBE reported here is
      consistent with the majority of measurements, both in vitro and in vivo, by other
      investigators. The dose dependence of RBE, on the other hand, is tissue specific
      but has not yet been demonstrated for protons by RBE values in late-responding
      normal tissue systems. This indicates a need for additional RBE determination as
      function of dose, especially in late-responding tissues.

PMID- 25587742
TI  - Brain injury special edition on sports concussion.

PMID- 25587743
TI  - Neurochemical cascade of concussion.
AB  - PRIMARY OBJECTIVE: The aim of this literature review was to systematically
      describe the sequential metabolic changes that occur following concussive injury,
      as well as identify and characterize the major concepts associated with the
      neurochemical cascade. RESEARCH DESIGN: Narrative literature review. CONCLUSIONS:
      Concussive injury initiates a complex cascade of pathophysiological changes that
      include hyper-acute ionic flux, indiscriminant excitatory neurotransmitter
      release, acute hyperglycolysis and sub-acute metabolic depression. Additionally,
      these metabolic changes can subsequently lead to impaired neurotransmission,
      alternate fuel usage and modifications in synaptic plasticity and protein
      expression. The combination of these metabolic alterations has been proposed to
      cause the transient and prolonged neurological deficits that typically
      characterize concussion. Consequently, understanding the implications of the
      neurochemical cascade may lead to treatment and return-to-play guidelines that
      can minimize the chronic effects of concussive injury.

PMID- 25587744
TI  - Chronic traumatic encephalopathy: contributions from the Boston University Center
      for the Study of Traumatic Encephalopathy.
AB  - OBJECTIVE: Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease
      associated with repetitive brain trauma (RBT). Initially described in boxers, CTE
      has now been found in other contact sport athletes with a history of RBT. In
      recent years, there has been tremendous media attention regarding CTE, primarily
      because of the deaths of high profile American football players who were found to
      have CTE upon neuropathological examination. However, the study of CTE remains in
      its infancy. This review focuses on research from the Centre for the Study of
      Traumatic Encephalopathy (CSTE) at Boston University. METHODS: This study reviews
      the formation of the CSTE, major CSTE publications and current ongoing research
      projects at the CSTE. RESULTS: The neuropathology of CTE has been well-described.
      Current research focuses on: methods of diagnosing the disease during life
      (including the development of biomarkers), examination of CTE risk factors
      (including genetic susceptibility and head impact exposure variables);
      description of the clinical presentation of CTE; development of research
      diagnostic criteria for Traumatic Encephalopathy Syndrome; and assessment of
      mechanism and pathogenesis. CONCLUSIONS: Current research at the BU CSTE is aimed
      at increasing understanding of the long-term consequences of repetitive head
      impacts and attempting to begin to answer several of the unanswered questions
      regarding CTE.

PMID- 25587745
TI  - Developing guidelines for return to play: consensus and evidence-based
      approaches.
AB  - BACKGROUND: Sports-related concussions are commonplace at all levels of play and
      across all age groups. The dynamic, evolving nature of this injury coupled with a
      lack of objective biomarkers creates a challenging management issue for the
      sports medicine team. Athletes who return to play following a concussion are
      known to be at higher risk for an additional brain injury, which necessitates a
      careful, informed return to play (RTP) process. AIM: The goal of this paper is to
      outline historical attempts at developing RTP guidelines and trace their
      evolution over time, culminating in a discussion of the process and outcomes of
      the most recent consensus statements/guidelines published by the international
      Concussion In Sport Group (CISG), the American Academy of Neurology (AAN), the
      National Athletic Trainers' Association, and the 2013 Team Physician Consensus
      Statement Update. METHOD: An evaluation of the pros and cons of these guidelines
      is presented along with suggestions for future directions. In addition, the
      Institute of Medicine recently conducted a comprehensive report outlining the
      current state of evidence regarding youth concussions, which provides specific
      recommendations for future research. CONCLUSIONS: The different methodologies
      utilized in the development of consensus statements have distinct advantages and
      disadvantages, and both approaches add value to the everyday management of sports
      concussions. Importantly, the overall approach for management of sports
      concussion is remarkably similar using either consensus-based or formal evidence
      based methods, which adds confidence to the current guidelines and allows
      practitioners to focus on accepted standards of clinical care. Moving forward,
      careful study designs need to be utilized to avoid bias in selection of research
      subjects, collection of data, and interpretation of results. Although useful,
      clinicians must venture beyond consensus statements to examine reviews of the
      literature that are published in much greater frequency than consensus
      statements.

PMID- 25587746
TI  - Sleep disturbances in athletic concussion.
AB  - BACKGROUND: Sleep disturbances are a common symptom following concussions to
      include athletic concussion. REVIEW: This review applies literature on sleep
      following traumatic brain injury and concussion to sport concussions and places
      these considerations in the context of sleep and athletic performance. It also
      includes a description of sleep abnormalities in sleep duration, quality and
      timing as well as recommended treatment approaches. Finally, it includes a brief
      discussion of emerging paradigms of sleep and concussion recovery.

PMID- 25587747
TI  - Acceptability, feasibility, and efficacy of a supportive group intervention for
      caregivers of newly diagnosed leukemia patients.
AB  - This study describes the development of a supportive group-based intervention for
      family caregivers of newly diagnosed leukemia patients. We assessed the
      feasibility, acceptability, and efficacy of the group on caregiver distress and
      quality of life, as well as patient distress utilizing a sequential cohort design
      comparing a pre-intervention control group with the intervention group. Patients
      and caregiver dyads completed measures at 4 time points: within 1 week of
      diagnosis (T1), 2-week follow-up (T2), 6-week follow-up (T3), and 12-week follow
      up (T4). Significant interaction effects were observed for both caregiver
      distress and quality of life, whereby those receiving the intervention
      demonstrated improved quality of life and reduced distress over time. Overall,
      results support the acceptability, feasibility, and preliminary efficacy of the
      group intervention. 

PMID- 25587748
TI  - Simultaneous utilization of cellobiose, xylose, and acetic acid from
      lignocellulosic biomass for biofuel production by an engineered yeast platform.
AB  - The inability of fermenting microorganisms to use mixed carbon components derived
      from lignocellulosic biomass is a major technical barrier that hinders the
      development of economically viable cellulosic biofuel production. In this study,
      we integrated the fermentation pathways of both hexose and pentose sugars and an
      acetic acid reduction pathway into one Saccharomyces cerevisiae strain for the
      first time using synthetic biology and metabolic engineering approaches. The
      engineered strain coutilized cellobiose, xylose, and acetic acid to produce
      ethanol with a substantially higher yield and productivity than the control
      strains, and the results showed the unique synergistic effects of pathway
      coexpression. The mixed substrate coutilization strategy is important for making
      complete and efficient use of cellulosic carbon and will contribute to the
      development of consolidated bioprocessing for cellulosic biofuel. The study also
      presents an innovative metabolic engineering approach whereby multiple substrate
      consumption pathways can be integrated in a synergistic way for enhanced
      bioconversion. 

PMID- 25587749
TI  - Designing micellar nanocarriers with improved drug loading and stability based on
      solubility parameter.
AB  - The objective of this study is to demonstrate the feasibility of using solubility
      parameter as guidance for the design and identification of a stable micellar
      system with a high drug loading capacity for oral drug delivery. Using
      hydroxycamptothecin (HCPT) as a model drug, the effect of three hydrophobic
      blocks (fatty glycerides) grafted onto chitosan on the drug loading and stability
      of HCPT-loaded micellar nanoparticles formed by pH precipitation method were
      studied systematically. The Flory-Huggins interaction parameter (chiFH)
      calculated by the group contribution method (GCM) and molecular dynamics
      simulation (MDS) was used to assess the compatibility between HCPT and the
      copolymers. The predicted order of compatibility between three chitosan
      derivatives and HCPT was verified experimentally. A high drug loading and
      remarkably stable micellar system for oral administration based on succinylated
      glycerol monooleate-chitosan was discovered in this study. Our study suggests
      that the miscibility between drug and copolymer is crucial to drug loading and
      stability of the micellar system. Thus, the calculation of chiFH using GCM and
      MDS methods is useful for guiding the design or screening of a suitable copolymer
      for preparing drug-loaded micellar nanocarrier systems. 

PMID- 25587750
TI  - Chemical bath deposition of ZnO on functionalized self-assembled monolayers:
      selective deposition and control of deposit morphology.
AB  - We have developed a method by which to selectively and reproducibly deposit ZnO
      films on functionalized self-assembled monolayers (SAMs) using chemical bath
      deposition (CBD). The deposition bath is composed of zinc acetate and
      ethylenediamine. The deposition reaction pathways are shown to be similar to
      those observed for sulfides and selenides, even though ethylenediamine acts as
      both an oxygen source and a complexing agent. On -COOH terminated SAMs, Zn
      carboxylate surface complexes act as nucleation sites for ion-by-ion growth,
      leading to the formation of adherent ZnO nanocrystallites. Cluster-by-cluster
      growth is also observed, which produces weakly adherent micrometer-sized ZnO
      crystallites. On -CH3 and -OH terminated SAMs, only micrometer-sized ZnO
      crystallites are observed because Zn(2+) does not complex with the SAM terminal
      group, preventing nucleation of the nanocrystalline phase. The application of
      either ultrasound ("sonication-assisted CBD") or stirring promotes ion-by-ion ZnO
      growth on -COOH terminated SAMs. Stirring produces smoother but less reproducible
      ZnO films than sonication-assisted CBD. 

PMID- 25587751
TI  - TRIM proteins regulate autophagy: TRIM5 is a selective autophagy receptor
      mediating HIV-1 restriction.
AB  - The tripartite motif protein family (TRIM) constitutes a class of immune
      regulated proteins with antiviral, immune, cancer, and other properties
      reminiscent of those ascribed to autophagy. We show that TRIMs have dual roles in
      autophagy: as regulators and as cargo receptors. As regulators, TRIMs nucleate
      the core autophagy machinery by acting as platforms that assemble ULK1 and BECN1
      into a functional complex in preparation for autophagy. TRIMs also act as novel
      selective autophagy receptors as exemplified by TRIM5/TRIM5alpha, a known HIV-1
      restriction factor with a hitherto poorly defined mode of action. TRIM5
      recognizes and targets HIV-1 for autophagic destruction. TRIM5 interactions with
      mammalian Atg8 proteins are required for this effector function. This establishes
      TRIM family members as regulators of autophagy, explains the antiretroviral
      mechanism of TRIM5, and defines a new basis for selective autophagy. 

PMID- 25587752
TI  - Ruthenium sensitizers with a hexylthiophene-modified terpyridine ligand for dye
      sensitized solar cells: synthesis, photo- and electrochemical properties, and
      adsorption behavior to the TiO2 surface.
AB  - Two novel ruthenium sensitizers with a hexylthiophene-modified terpyridine ligand
      (TUS-35 and TUS-36) were synthesized to improve the molar absorptivity of the
      previously reported ruthenium sensitizer (TBA)[Ru{4'-(3,4-dicarboxyphenyl)-4,4"
      dicarboxyterpyridine}(NCS)3], TBA = tetrabutylammonium (TUS-21). A relatively
      strong absorption appeared at ~380 nm, and the molar absorption coefficient at
      the metal-to-ligand charge transfer (MLCT) band decreased in TUS-35 by
      introducing a 2-hexylthiophene unit to the 5-position of the terpyridine-derived
      ligand. For comparison, a relatively strong absorption was observed at ~350 nm
      without decreasing the molar absorption coefficient at the MLCT band in TUS-36 by
      introducing a 2-hexylthiophene unit to the 4-position of the terpyridine-derived
      ligand. On the other hand, the energy levels of the highest occupied molecular
      orbitals and the lowest unoccupied molecular orbitals of these two sensitizers
      were found to be almost equal to those of TUS-21. The adsorption behavior of TUS
      35 and TUS-36 was similar to that of (TBA)[Ru{4'-(3,4
      dicarboxyphenyl)terpyridine}(NCS)3] (TUS-20), which binds to the TiO2 surface by
      using the 3,4-dicarboxyphenly unit, rather than that of TUS-21, which adsorbs to
      the TiO2 photoelectrode using one of the carboxyl groups at the terminal
      pyridines of the terpyridine-derived ligand. Therefore, TUS-35 and TUS-36 are
      considered to bind to the TiO2 surface by using the 3,4-dicarboxyphenly unit just
      like TUS-20. The dye-sensitized solar cells (DSCs) with TUS-35 and TUS-36 showed
      a relatively lower conversion efficiency (6.4% and 5.7%, respectively) compared
      to the DSC with TUS-21 (10.2%). Open-circuit photovoltage decay and
      electrochemical impedance spectroscopy measurements revealed that the promoted
      charge recombination and/or charge transfer of the injected electrons in the TiO2
      photoelectrode is a main reason for the inferior performances of TUS-35 and TUS
      36. 

PMID- 25587753
TI  - Low-temperature NMR characterization of reaction of sodium pyruvate with hydrogen
      peroxide.
AB  - It was proposed that the reaction of sodium pyruvate and H2O2 generates the
      intermediate 2-hydroperoxy-2-hydroxypropanoate, which converts into acetate, CO2,
      and H2O ( Aleksankin et al. Kernenergie 1962 , 5 , 362 - 365 ). These conclusions
      were based on the products generated in (18)O-enriched water and H2O2 reacting
      with pyruvic acid at room temperature; however, the lifetime of 2-hydroperoxy-2
      hydroxypropanoate at room temperature is too short for direct spectroscopic
      observation. Therefore, we applied the combination of low-temperature and (13)C
      NMR techniques to verify, for the first time, the formation of 2-deuteroperoxy-2
      deuteroxypropanoate in mixtures of D2O and methanol-d4 and to monitor directly
      each species involved in the reaction between D2O2 and (13)C-enriched pyruvate.
      Our NMR results confirm the formation of 2-deuteroperoxy-2-deuteroxypropanoate,
      where the respective chemical shifts are supported by density functional theory
      (DFT) calculations. At near-neutral apparent pD (pD*) and -35  degrees C, the
      formation of 2-deuteroperoxy-2-deuteroxypropanoate occurred with k = 2.43 * 10(
      3) dm(3).mol(-1).s(-1). The subsequent decomposition of 2-deuteroperoxy-2
      deuteroxypropanoate into acetate, CO2, and D2O occurred with k = 2.58 * 10(-4) s(
      1) at -35  degrees C. In order to provide a full kinetic analysis, we also
      monitored the equilibrium of pyruvate and methanol with the hemiacetal (2
      deuteroxy-2-methoxypropanoate). The kinetics for the reaction of sodium pyruvate
      and D2O2 were fitted by taking into account all these equilibria and species. 

PMID- 25587754
TI  - Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein
      kinase R-like endoplasmic reticulum kinase (PERK).
AB  - The structure-based design and optimization of a novel series of selective PERK
      inhibitors are described resulting in the identification of 44 as a potent,
      highly selective, and orally active tool compound suitable for PERK pathway
      biology exploration both in vitro and in vivo. 

PMID- 25587756
TI  - Help your institution's reputation and publish in Analytical Chemistry.

PMID- 25587755
TI  - Bronchodilating drugs for chronic obstructive pulmonary disease: current status
      and future trends.
AB  - Inhaled bronchodilators, including long-acting muscarinic receptor antagonists
      (LAMA) and long-acting beta2-adrenoreceptor agonists (LABA), are the mainstay of
      pharmacological treatment of stable chronic obstructive pulmonary disease (COPD).
      Among approved LAMA, tiotropium bromide, glycopyrronium bromide, and umeclidinium
      bromide are administered once daily, whereas aclidinium bromide is administered
      every 12 h. New LAMA are under development for COPD. Among the approved LABA,
      indacaterol has a 24 h duration of action, whereas salmeterol and formoterol
      require twice-daily administration. New once-daily LABA, including vilanterol,
      olodaterol, milveterol, carmoterol, and abediterol, are in development. LAMA/LABA
      fixed dose combinations (FDCs) provide the convenience of two bronchodilators
      with different mechanism of action in a single inhaler.
      Indacaterol/glycopyrronium, umeclidinium/vilanterol, and olodaterol/tiotropium
      FDCs have been approved or are under approval and are likely to become a standard
      pharmacological strategy for COPD. Inhaled dual-pharmacology compounds, combining
      muscarinic antagonism and beta2-agonism (MABA) in a single molecule, potentially
      provide additive or synergistic bronchodilation over either inhaled
      antimuscarinic or beta2-agonist monotherapy. 

PMID- 25587757
TI  - Clinical application of a custom AmpliSeq library and ion torrent PGM sequencing
      to comprehensive mutation screening for deafness genes.
AB  - BACKGROUND: Congenital hearing loss is one of the most common sensory disorders,
      with 50-70% of cases attributable to genetic causes. Although recent advances in
      the identification of deafness genes have resulted in more accurate molecular
      diagnosis, leading to the better determination of suitable clinical
      interventions, difficulties remain with regard to clinical applications due to
      the extreme genetic heterogeneity of deafness. AIM: Toward more effective genetic
      testing, we adopted Massively Parallel DNA Sequencing (MPS) of target genes using
      an Ion PGMTM system and an Ion AmpliSeqTM panel to diagnose common mutations
      responsible for deafness and discover rare causative gene mutations. Before its
      clinical application, we investigated the accuracy of MPS-based genetic testing.
      RESULTS: We compared the results of Invader assay-based genetic screening, the
      accuracy of which has already been verified in previous studies, with those of
      MPS-based genetic testing for a large population of Japanese deafness patients
      and revealed that over 99.98% of the results were the same for each genetic
      testing system. CONCLUSION: The Ion Personal Genome Machine system had sufficient
      uniformity and accuracy for application to the clinical diagnosis of common
      causative mutations and efficiently identified rare causative mutations and/or
      mutation candidates.

PMID- 25587758
TI  - Cardiovascular risk and metabolic syndrome in obese youth enrolled in a
      multidisciplinary medical weight management program: implications of
      musculoskeletal pain, cardiorespiratory fitness, and health-related quality of
      life.
AB  - BACKGROUND: Obese youth demonstrate the same obesity-associated morbidities
      observed in obese adults, including poor cardiorespiratory fitness, poor quality
      of life, and reports of musculoskeletal pain. The purposes of this study were to
      compare the prevalence of cardiovascular risk factors and evaluate the odds of
      metabolic syndrome in obese youth based on measures of cardiorespiratory fitness,
      quality of life, and pain. METHODS: A medical chart review of 183 obese youth in
      a medical weight management program was conducted. Measures of cardiovascular
      risk and metabolic syndrome were recorded. Groups were categorized based on
      Progressive Aerobic Cardiovascular Endurance Run (PACER) score, Pediatric Quality
      of Life (PedsQL)-Physical Function score, PedsQL-Psychosocial Health score, and
      reports of musculoskeletal pain. Statistical analysis included independent t
      tests, Mann-Whitney U-test, chi-squared test, and logistic regression. RESULTS:
      Thirty-three percent of the entire sample had C-reactive protein (CRP) levels
      >3.0 mg/dL and 30% were categorized as having metabolic syndrome. Patients with
      lower PACER scores demonstrated a greater prevalence of CRP levels >3.0 mg/dL
      versus those with higher PACER scores (45% vs. 12%; P=0.01). There were no other
      differences in the prevalence of cardiovascular risk factors or metabolic
      syndrome when categorized by PACER, PedsQL, or pain. Those with CRP levels >3.0
      mg/dL demonstrated increased odds of metabolic syndrome-[odds (95% confidence
      interval, CI): 4.93 (1.24-19.61); P=0.02]. CONCLUSIONS: Overall, results do not
      show differences in cardiovascular risk in obese youth when categorized by PACER,
      PedsQL, or reports of MSK pain. Elevated CRP may be a useful predictor of
      metabolic syndrome in obese youth and warrants further investigation.

PMID- 25587771
TI  - Dopamine-melanin nanofilms for biomimetic structural coloration.
AB  - This article describes the formation of dopamine-melanin thin films (50-200 nm
      thick) at an air/dopamine solution interface under static conditions. Beneath
      these films, spherical melanin granules formed in bulk liquid phase. The
      thickness of dopamine-melanin films at the interface relied mainly on the
      concentration of dopamine solution and the reaction time. A plausible mechanism
      underlining dopamine-melanin thin film formation was proposed based on the
      hydrophobicity of dopamine-melanin aggregates and the mass transport of the
      aggregates to the air/solution interface as a result of convective flow. The
      thickness of the interfacial films increased linearly with the dopamine
      concentration and the reaction time. The dopamine-melanin thin film and granules
      (formed in bulk liquid phase) with a double-layered structure were transferred
      onto a solid substrate to mimic the (keratin layer)/(melanin granules) structure
      present in bird plumage, thereby preparing full dopamine-melanin thin-film
      reflectors. The reflected color of the thin-film reflectors depended on the film
      thickness, which could be adjusted according to the dopamine concentration. The
      reflectance of the resulted reflectors exhibited a maximal reflectance value of 8
      11%, comparable to that of bird plumage (~11%). This study provides a useful,
      simple, and low-cost approach to the fabrication of biomimetic thin-film
      reflectors using full dopamine-melanin materials. 

PMID- 25587772
TI  - Intramolecular cycloadditions of photogenerated azaxylylenes with oxadiazoles
      provide direct access to versatile polyheterocyclic ketopiperazines containing a
      spiro-oxirane moiety.
AB  - Photogenerated azaxylylenes undergo intramolecular cycloadditions to 1,3,4
      oxadiazole pendants, which are accompanied by concomitant release of dinitrogen,
      yielding functionalized ketopiperazinoquinolinols containing an oxirane moiety
      fused to the quinolinole moiety while spiro-connected to diketopiperazine. These
      primary photoproducts are reactive versatile intermediates which can be further
      derivatized under nucleophilic SN1- or SN2-like ring opening of the oxirane
      moiety. The oxidized quinolinones undergo new rearrangements under the conditions
      of the Schmidt reaction, leading to unprecedented triazacanoindolinones. 

PMID- 25587774
TI  - Sequencing analysis and characterization of the plasmid pBIF10 isolated from
      Bifidobacterium longum.
AB  - A resident plasmid, pBIF10, was isolated from Bifidobacterium longum B200304, and
      the full-length sequence of pBIF10 was analyzed. In this sequence, we identified
      at least 17 major open reading frames longer than 200 bp. A tetracycline
      resistance gene, tetQ, was identified and verified to confer antibiotic
      resistance to tetracycline. The plasmid replicon with replication protein B gene
      (repB) and a typical iteron was identified in pBIF10. An artificial clone vector
      was constructed with the replicon of pBIF10; the results showed that repB
      controlled plasmid replication in other bifidobacteria host cells at low
      transformation frequency. Taken together, the analysis and characterization of
      pBIF10 provided necessary information for the understanding of antibiotic
      resistance mediated by a plasmid in a Bifidobacterium strain. GC% and repB
      sequence analyses indicated that pBIF10 was a molecular hybrid of at least 2
      other bacterial genera plasmids. 

PMID- 25587775
TI  - A review of gene therapy in canine and feline models of lysosomal storage
      disorders.
AB  - Lysosomal storage disorders (LSDs) are inherited diseases that result from the
      intracellular accumulation of incompletely degraded macromolecules. The majority
      of LSDs affect both the peripheral and central nervous systems and are not
      effectively treated by enzyme replacement therapy, substrate reduction therapy,
      or bone marrow transplantation. Advances in adeno-associated virus and retroviral
      vector development over the past decade have resurged gene therapy as a promising
      therapeutic intervention for these monogenic diseases. Animal models of LSDs
      provide a necessary intermediate to optimize gene therapy protocols and assess
      the safety and efficacy of treatment prior to initiating human clinical trials.
      Numerous LSDs are naturally occurring in large animal models and closely
      reiterate the lesions, biochemical defect, and clinical phenotype observed in
      human patients, and whose lifetime is sufficiently long to assess the effect on
      symptoms that develop later in life. Herein, we review that gene therapy in large
      animal models (dogs and cats) of LSDs improved many manifestations of disease,
      and may be used in patients in the near future.

PMID- 25587773
TI  - Blood diagnostic biomarkers for major depressive disorder using multiplex DNA
      methylation profiles: discovery and validation.
AB  - Aberrant DNA methylation in the blood of patients with major depressive disorder
      (MDD) has been reported in several previous studies. However, no comprehensive
      studies using medication-free subjects with MDD have been conducted. Furthermore,
      the majority of these previous studies has been limited to the analysis of the
      CpG sites in CpG islands (CGIs) in the gene promoter regions. The main aim of the
      present study is to identify DNA methylation markers that distinguish patients
      with MDD from non-psychiatric controls. Genome-wide DNA methylation profiling of
      peripheral leukocytes was conducted in two set of samples, a discovery set (20
      medication-free patients with MDD and 19 controls) and a replication set (12
      medication-free patients with MDD and 12 controls), using Infinium
      HumanMethylation450 BeadChips. Significant diagnostic differences in DNA
      methylation were observed at 363 CpG sites in the discovery set. All of these
      loci demonstrated lower DNA methylation in patients with MDD than in the
      controls, and most of them (85.7%) were located in the CGIs in the gene promoter
      regions. We were able to distinguish patients with MDD from the control subjects
      with high accuracy in the discriminant analysis using the top DNA methylation
      markers. We also validated these selected DNA methylation markers in the
      replication set. Our results indicate that multiplex DNA methylation markers may
      be useful for distinguishing patients with MDD from non-psychiatric controls. 

PMID- 25587776
TI  - Metabolism of (14)C-labeled polychlorinated biphenyl congeners by wheat cell
      suspension cultures.
AB  - The metabolism of [UL-(14)C]-2,2',5,5'-tetrachlorobiphenyl ((14)C-PCB-52), [UL
      (14)C]-2,2',4,4',5,5'-hexachlorobiphenyl ((14)C-PCB-153, and a congeneric mixture
      of [UL-(14)C]-labeled polychlorinated biphenyls ((14)C-PCB-Mix) was studied in
      cell suspension cultures of wheat (Triticum aestivum L. cv. 'Heines Koga II').
      About 50% of applied (14)C-PCB-52 (20 MUg/assay) was transformed during 96 h of
      incubation. While 7.6% on non-extractable residues emerged, turnover of (14)C-PCB
      52 was mainly due to soluble polar metabolites. These were subjected to chemical
      glycoside cleavage. In the resulting hydrolysate, four aglycons were identified
      by GC-EIMS, namely four tetrachloro-hydroxy-biphenyl isomers (C6H6Cl4O, M(+.) at
      m/z = 306, 308, 310 and 312), and one trichloro-hydroxy-biphenyl (C6H7Cl3O, M(+.)
      at m/z = 272, 274 and 276). Number and character of hydroxylated products pointed
      to cytochromes P450 as enzymatic catalysts of hydroxylation. (14)C-PCB-153 was
      metabolized by wheat to minor degree if at all. Due to GC-EIMS analysis, of (14)C
      PCB-Mix consisted of biphenyl, one mono-, four di-, seven tri-, eleven tetra-,
      and four pentachlorobiphenyls besides traces of further mono- and
      hexachlorobiphenyls. Among these were PCB-28, PCB-52, PCB 101, and PCB-118
      (identified by seven key congeners standard). The mixture resembled industrial
      products Clophen A30 or Aroclor 1016. Metabolic turnover of applied (14)C-PCB-Mix
      (15 MUg/assay) was 30% after 96 h; 8.4% of non-extractable residues emerged.
      Using DDE (p,p'-dichlorodiphenyl-dichloroethylene) as internal standard it was
      demonstrated that biphenyl, one monochloro-, two dichloro-, and one
      trichlorobiphenyl were completely metabolized to polar products. Partial
      metabolization occurred with one di-, five tri-, and four tetrachlorobiphenyls.
      Two tri-, four tetra-, and all pentachlorbiphenyls proved to be stable. Due to
      strong interference by matrix, evaluation of three congeners was not possible. In
      addition to wheat, results of similar experiments with cell cultures of other
      species are briefly mentioned. 

PMID- 25587777
TI  - Biodegradation of endosulfan isomers and its metabolite endosulfate by two
      biosurfactant producing bacterial strains of Bordetella petrii.
AB  - The main objective of the investigation was to study the biodegradation of
      endosulfan isomers and its major metabolite endosulfate by two biosurfactant
      producing bacterial strains of Bordetella petrii. The significance of the study
      is to evaluate the capability of biosurfactant producing bacterial strains in
      enhancing the bioavailability of endosulfan. Sixty bacterial strains were
      isolated from the endosulfan degrading bacterial consortium and were screened for
      endosulfan degradation and biosurfactant production. Among those, two strains
      Bordetella petrii I GV 34 (Gene bank Accession No KJ02262) and Bordetella petrii
      II GV 36 (Gene bank Accession No KJ022625) were capable of degrading endosulfan
      with simultaneous biosurfactant production. Bordetella petrii I degraded 89% of
      alpha and 84% of beta isomers of endosulfan whereas Bordetella petrii II degraded
      82% of both the isomers. Both the strains were able to reduce the surface tension
      up to 19.6% and 21.4% with a minimum observed surface tension of 45 Dynes/cm and
      44 Dynes/cm, respectively. The study revealed that the strains have the potential
      to enhance the degradation endosulfan residues in contaminated sites and water by
      biosurfactant production.

PMID- 25587778
TI  - Kresoxim methyl dissipation kinetics and its residue effect on soil extra
      cellular and intra-cellular enzymatic activity in four different soils of India.
AB  - The rate of degradation of kresoxim methyl and its effect on soil extra-cellular
      (acid phosphatase, alkaline phosphatase and beta-glucosidase) and intra-cellular
      (dehydrogenase) enzymes were explored in four different soils of India. In all
      the tested soils, the degradation rate was faster at the beginning, which slowed
      down with time indicating a non-linear pattern of degradation. Rate of
      degradation in black soil was fastest followed by saline, brown and red soils,
      respectively and followed 1st or 1st + 1st order kinetics with half-life ranging
      between 1-6 days for natural soil and 1-19 days for sterile soils. The rate of
      degradation in natural against sterilized soils suggests that microbial
      degradation might be the major pathway of residue dissipation. Although small
      changes in enzyme activities were observed, kresoxim methyl did not have any
      significant deleterious effect on the enzymatic activity of the various test
      soils in long run. Simple correlation studies between degradation percentage and
      individual enzyme activities did not establish any significant relationships. The
      pattern and change of enzyme activity was primarily due to the effect of the
      incubation period rather than the effect of kresoxim methyl itself.

PMID- 25587779
TI  - Evaluation of hydrocarbons and organochlorine pesticides and their tolerant
      microorganisms from an agricultural soil to define its bioremediation
      feasibility.
AB  - The concentrations of hydrocarbons and organochlorine pesticides (OCPs),
      nutrients and tolerant microorganisms in an agricultural soil from a locality in
      Tepeaca, Puebla, Mexico, were determined to define its feasibility for
      bioremediation. The OCPs detected were heptachlor, aldrin, trans-chlordane,
      endosulfan I, endosulfan II, 1,1,1-bis-(4-chlorophenyl)-2,2-trichloroethane (4,4'
      DDT), 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (4,4'-DDE) and endrin aldehyde,
      with values of 0.69-30.81 ng g(-1). The concentration of hydrocarbons in the soil
      of Middle Hydrocarbons Fraction (MHF), C10 to C28, was 4608-27,748 mg kg(-1) and
      1117-19,610 mg kg(-1) for Heavy Hydrocarbons Fraction (HHF), C28 to C35, due to
      an oil spill from the rupture of a pipeline. The soil was deficient in nitrogen
      (0.03-0.07%) and phosphorus (0 ppm), and therefore it was advisable to fertilize
      to bio-stimulate the native microorganisms of soil. In the soil samples,
      hydrocarbonoclast fungi 3.72 * 10(2) to 44.6 * 10(2) CFU g(-1) d.s. and
      hydrocarbonoclast bacteria (0.17 * 10(5) to 8.60 * 10(5) CFU g(-1) d.s.) were
      detected, with a tolerance of 30,000 mg kg(-1) of diesel. Moreover,
      pesticideclast fungi (5.13 * 10(2) to 42.2 * 10(2) CFU g(-1) d.s.) and
      pesticideclast bacteria (0.15 * 10(5) to 9.68 * 10(5) CFU g(-1) d.s.) were
      determined with tolerance to 20 mg kg(-1) of OCPs. Fungi and bacteria tolerant to
      both pollutants were also quantified. Therefore, native microorganisms had
      potential to be stimulated to degrade hydrocarbons and pesticides or both
      pollutants. The concentration of pollutants and the microbial activity analyzed
      indicated that bioremediation of the soil contaminated with hydrocarbons and
      pesticides using bio-stimulation of native microorganisms was feasible.

PMID- 25587780
TI  - Determination of pesticide residues in animal origin baby foods by gas
      chromatography coupled with triple quadrupole mass spectrometry.
AB  - A simple, fast and multiresidue method for the determination of pesticide
      residues in baby foods of animal origin has been developed in order to check the
      compliance with the Maximum Residue Levels (MRLs) set at a general value of 0.01
      mg/kg by Commission Directive 2006/125/EC for infant foods. The main classes of
      organochlorine, organophosphorus and pyrethroid compounds have been considered,
      which are mainly fat soluble pesticides. The analytical procedure consists in the
      extraction of baby food samples by acetonitrile (ACN) followed by a clean up
      using C18 solid-phase extraction column eluted with ACN. The compounds were
      determined by gas chromatography-triple quadrupole mass spectrometry equipped
      with a Programmed Temperature Vaporizer (PTV) injection and a backflush system.
      In order to compensate for matrix effects PTV and matrix matched standard
      calibrations have been used. The method has been fully validated for 57
      pesticides according to the Document SANCO/12571/2013. Accuracy and precision
      (repeatability) have been studied by recoveries at two spiking levels, the Limit
      of Quantitation (LOQ) (0.003-0.008 mg/kg) and 10 time greater (0.03-0.08 mg/kg),
      and the results were in the acceptable range of 70-120% with Relative Standards
      Deviations (RSD) <=20%. Selectivity, linearity, LOQ and uncertainty of
      measurement were also determined for all the compounds. The method has been also
      applied for the analysis of 18 baby food animal origin samples, bought form the
      local market in Rome (Italy), and no pesticide in the scope of the method has
      been found above the MRL or the LOQ. 

PMID- 25587781
TI  - Urinary phytoestrogens in relation to metabolic disturbances among children and
      adolescents.
AB  - Previous studies have examined whether phytoestrogens affect glucose and lipid
      metabolism. However, data on children and adolescents are still limited, with
      most of the evidence pertaining to one phytoestrogen, namely genistein. To
      investigate the effect of six phytoestrogens [daidezin, enterodiol,
      enterolactone, equol, genistein and O-Desmethylangolensin (O-DMA)] on metabolic
      disturbances among youths, a cross-sectional study was conducted using a sample
      of 2,429 children and adolescents, 6-18 years, from the 2009-2010 National Health
      and Nutrition Examination Surveys (NHANES). The main outcome measures were body
      mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP),
      high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and total
      cholesterol (TC), fasting glucose, triglycerides and glycohemoglobin. SBP was
      inversely related to enterolactone and equol. Triglycerides were inversely
      related to daidezin, equol, genistein and O-DMA. Whereas TC and LDL-C were
      inversely related to equol, an HDL-C was inversely related to genistein and O
      DMA. Whereas fasting glucose was associated with enterodiol (beta = 0.33, 95% CI:
      0.028, 0.63), a positive relationship was observed between enterodiol and risk of
      HDL-C >= 35 mg dl(-1) (beta = 0.04, 95% CI: 0.01, 0.07). In conclusion, certain
      phytoestrogens may contribute either positively or negatively to disturbances in
      lipid and glucose metabolism. Large prospective cohort studies are needed to
      confirm our study findings.

PMID- 25587782
TI  - Assessment of T-2 toxin effect and its metabolite HT-2 toxin combined with
      insulin-like growth factor I, leptin and ghrelin on progesterone secretion by
      rabbit ovarian fragments.
AB  - Assessment of A-trichothecene mycotoxins (T-2 and HT-2 toxins) effect combined
      with growth factor IGF-I, and the metabolic hormones leptin and ghrelin on
      progesterone secretion by rabbit ovarian fragments was studied. Rabbit ovarian
      fragments were incubated without (control group) or with T-2/HT-2 toxin, or their
      combinations with insulin-like growth factor I (IGF-I), leptin or ghrelin at
      various concentrations for 24 h. Secretion of progesterone was determined by
      ELISA. First, T-2 toxin and HT-2 toxins at all doses used (0.01, 0.1, 1, 10, and
      100 ng mL(-1)) were not shown to be potential regulators of progesterone
      secretion in rabbit ovarian fragments. Second, T-2 toxin but not HT-2 toxin
      combined with IGF-I was shown to be potential regulator of progesterone secretion
      in rabbit ovarian fragments. T-2 toxin at all doses used (0.01; 0.1; 1; 10; and
      100 ng mL(-1)) combined with IGF-I (at dose 100 ng mL(-1)) significantly (P <
      0.05) decreased progesterone secretion by rabbit ovarian fragments. Third, T-2
      toxin and HT-2 toxin at all doses used in the study (0.01, 0.1, 1, 10, and 100 ng
      mL(-1)) combined with leptin (at dose 1000 ng mL(-1)) were not shown to be
      potential regulators of progesterone secretion in rabbit ovarian fragments.
      Furthermore, T-2 toxin and HT-2 toxin at all doses used in the study (0.01, 0.1,
      1, 10, and 100 ng mL(-1)) combined with ghrelin (500 ng mL(-1)) were not shown to
      be potential regulators of progesterone secretion in rabbit ovarian fragments.
      Results in this study showed that trichothecene as T-2 toxin combined with IGF-I
      but not HT-2 toxin was able to decrease progesterone secretion in rabbit ovarian
      fragments in vitro. Experimental results of T-2 and HT-2 toxins combined with
      leptin and ghrelin did not confirm ability to modulate progesterone secretion by
      ovarian fragments in rabbits.

PMID- 25587783
TI  - An assessment of Salmonella survival in pig manure and its separated solid and
      liquid fractions during storage.
AB  - The objective of this study was to examine Salmonella survival in pig manure and
      its separated fractions during storage. Salmonella declined, but significant
      reductions were not observed in the manure and liquid until day 56, whereas
      counts in the solids were lower by day 7. The Salmonella inoculum initially
      impacted counts but not after days 28-56. By day 112 Salmonella was undetectable
      in the manure and liquid but was recovered from the solids. There was no clear
      dominance of particular serotypes and antibiotic resistance transfer was not
      found. Storage duration and pH impacted Salmonella counts in all samples, with
      duration having the greatest effect. Of the nutrients, nitrate had the greatest
      impact in the manure and, together with phosphate, it also affected counts in the
      liquid fraction. This study demonstrates that if pig manure or its separated
      fractions are stored under controlled conditions at 10.5 degrees C for 84-112
      days Salmonella is reduced or eliminated, irrespective of the initial load.

PMID- 25587784
TI  - Listeria monocytogenes batch culture growth response to metabolic inhibitors.
AB  - In certain environments nutrient and energy sources available to microorganisms
      can be limited. Foodborne pathogens must efficiently adapt in order to be
      successfully transmitted through the food chain to their hosts. For the
      intracellular foodborne pathogen Listeria monocytogenes, little is known
      regarding its response to nutrient/energy-limiting conditions. The alternative
      stress responsive sigma factor sigma(B) has been reported to contribute to
      survival under specific stresses. Therefore, the effects of several metabolic
      inhibitors on growth of L. monocytogenes wild-type and a DeltasigB mutant were
      examined. In the absence of inhibitors, both strains reached stationary phase
      after 18 h at 23 degrees C and 10 h at 37 degrees C. All of the metabolic
      inhibitors slowed growth of either strain, with few differences observed among
      the different inhibitors. 

PMID- 25587785
TI  - Synthesis and herbicidal activity of novel 1-(Diethoxy-phosphoryl)-3-(4-one-1H
      1,2,3-triazol-1-yl)-propan-2-yl carboxylic esters.
AB  - A series of novel compounds, namely 1-(diethoxyphosphoryl)-3-(4-ones-1H-1,2,3
      triazol-1-yl)propan-2-yl carboxylic esters, were designed on the basis of the
      diazafulvene intermediate of imidazole glycerol phosphate dehydratase (IGPD) and
      high-activity inhibitors of IGPD, and synthesized as inhibitors targeting IGPD in
      plants. Their structures were confirmed by 1H-NMR, 13C-NMR, 31P-NMR and HR-MS.
      The herbicidal evaluation performed by a Petri dish culture method showed that
      most compounds possessed moderate to good herbicidal activities. Six compounds
      were chosen for further herbicidal evaluation on barnyard grass by pot
      experiments. 1-(Diethoxyphosphoryl)-3-(4-phenyl-1H-1,2,3-triazol-1-yl)propan-2-yl
      2-(naphthalen-1-yl)acetate (5-A3) and ethyl 1-(2-acetoxy-3
      (diethoxyphosphoryl)propyl)-1H-1,2,3-triazole-4-carboxylate (5-B4) showed good
      herbicidal activities. Compared with the compounds with the best herbicidal
      activity ever reported, both compounds 5-A3 and 5-B4, which can inhibit the
      growth of barnyard grass at the concentration of 250g/hm2, efficiently gave rise
      to a nearly 4-fold increase of the herbicidal potency. However, their herbicidal
      activities were lower than that of acetochlor (62.5 g/hm2) in the pot
      experiments. 

PMID- 25587786
TI  - Novel pyrazine analogs of chalcones: synthesis and evaluation of their antifungal
      and antimycobacterial activity.
AB  - Infectious diseases, such as tuberculosis and invasive mycoses, represent serious
      health problems. As a part of our long-term efforts to find new agents for the
      treatment of these diseases, a new series of pyrazine analogs of chalcones
      bearing an isopropyl group in position 5 of the pyrazine ring was prepared. The
      structures of the compounds were corroborated by IR and NMR spectroscopy and
      their purity confirmed by elemental analysis. The susceptibility of eight fungal
      strains to the studied compounds was tested. The results have been compared with
      the activity of some previously reported propyl derivatives. The only strain that
      was susceptible to the studied compounds was Trichophyton mentagrophytes. It was
      found that replacing a non-branched propyl with a branched isopropyl did not have
      a decisive and unequivocal influence on the in vitro antifungal activity against
      T. mentagrophytes. In vitro activity against Trichophyton mentagrophytes
      comparable with that of fluconazole was exhibited by nitro-substituted
      derivatives. Unfortunately, no compound exhibited efficacy comparable with that
      of terbinafine, which is the most widely used agent for treating mycoses caused
      by dermatophytes. Some of the prepared compounds were assayed for
      antimycobacterial activity against M. tuberculosis H37Rv. The highest potency was
      also displayed by nitro-substituted compounds. The results of the present study
      are in a good agreement with our previous findings and confirm the positive
      influence of electron-withdrawing groups on the B-ring of chalcones on the
      antifungal and antimycobacterial activity of these compounds. 

PMID- 25587787
TI  - Phenolic content and antioxidant capacity in algal food products.
AB  - The study objective was to investigate total phenolic content using Folin
      Ciocalteu's method, to assess nine phenols by HPLC, to determine antioxidant
      capacity of the water soluble compounds (ACW) by a photochemiluminescence method,
      and to calculate the correlation coefficients in commercial algal food products
      from brown (Laminaria japonica, Eisenia bicyclis, Hizikia fusiformis, Undaria
      pinnatifida) and red (Porphyra tenera, Palmaria palmata) seaweed, green
      freshwater algae (Chlorella pyrenoidosa), and cyanobacteria (Spirulina
      platensis). HPLC analysis showed that the most abundant phenolic compound was
      epicatechin. From spectrophotometry and ACW determination it was evident that
      brown seaweed Eisenia bicyclis was the sample with the highest phenolic and ACW
      values (193 mg.g-1 GAE; 7.53 umol AA.g-1, respectively). A linear relationship
      existed between ACW and phenolic contents (r = 0.99). Some algal products seem to
      be promising functional foods rich in polyphenols. 

PMID- 25587788
TI  - The giant adhesin SiiE of Salmonella enterica.
AB  - Salmonella enterica is a Gram-negative, food-borne pathogen, which colonizes the
      intestinal tract and invades enterocytes. Invasion of polarized cells depends on
      the SPI1-encoded type III secretion system (T3SS) and the SPI4-encoded type I
      secretion system (T1SS). The substrate of this T1SS is the non-fimbrial giant
      adhesin SiiE. With a size of 595 kDa, SiiE is the largest protein of the
      Salmonella proteome and consists of 53 repetitive bacterial immunoglobulin (BIg)
      domains, each containing several conserved residues. As known for other T1SS
      substrates, such as E. coli HlyA, Ca2+ ions bound by conserved D residues within
      the BIg domains stabilize the protein and facilitate secretion. The adhesin SiiE
      mediates the first contact to the host cell and thereby positions the SPI1-T3SS
      to initiate the translocation of a cocktail of effector proteins. This leads to
      actin remodeling, membrane ruffle formation and bacterial internalization. SiiE
      binds to host cell apical membranes in a lectin-like manner. GlcNAc and alpha2-3
      linked sialic acid-containing structures are ligands of SiiE. Since SiiE shows
      repetitive domain architecture, we propose a zipper-like binding mediated by each
      individual BIg domain. In this review, we discuss the characteristics of the SPI4
      T1SS and the giant adhesin SiiE. 

PMID- 25587789
TI  - Synthesis of chromonylthiazolidines and their cytotoxicity to human cancer cell
      lines.
AB  - Nine new chromonylthiazolidine derivatives were successfully semi-synthesized
      from paeonol. All of the compounds, including starting materials, the
      intermediate compound and products, were evaluated for their cytotoxic effects
      toward eight human cancer cell lines. The synthesized chromonylthiazolidines
      displayed weak cytotoxic effects against the tested cancer cell lines, but
      selective cytotoxic effects were observed. Compounds 3a and 3b showed the most
      selective cytotoxic effects against human epidermoid carcinoma (IC50 44.1 +/- 3.6
      MUg/mL) and breast cancer (IC50 32.8 +/- 1.4 MUg/mL) cell lines, respectively.
      The results suggest that chromoylthiazolidines are potential low-cost, and
      selective anticancer agents. 

PMID- 25587790
TI  - Degradation dynamics of glyphosate in different types of citrus orchard soils in
      China.
AB  - Glyphosate formulations that are used as a broad-spectrum systemic herbicide have
      been widely applied in agriculture, causing increasing concerns about residues in
      soils. In this study, the degradation dynamics of glyphosate in different types
      of citrus orchard soils in China were evaluated under field conditions.
      Glyphosate soluble powder and aqueous solution were applied at 3000 and 5040 g
      active ingredient/hm2, respectively, in citrus orchard soils, and periodically
      drawn soil samples were analyzed by high performance liquid chromatography. The
      results showed that the amount of glyphosate and its degradation product
      aminomethylphosphonic acid (AMPA) in soils was reduced with the increase of time
      after application of glyphosate formulations. Indeed, the amount of glyphosate in
      red soil from Hunan and Zhejiang Province, and clay soil from Guangxi Province
      varied from 0.13 to 0.91 ug/g at 42 days after application of aqueous solution.
      Furthermore, the amount of glyphosate in medium loam from Zhejiang and Guangdong
      Province, and brown loam from Guizhou Province varied from less than 0.10 to 0.14
      ug/g, while the amount of AMPA varied from less than 0.10 to 0.99 ug/g at 42 days
      after application of soluble powder. Overall, these findings demonstrated that
      the degradation dynamics of glyphosate aqueous solution and soluble powder as
      well as AMPA depend on the physicochemical properties of the applied soils, in
      particular soil pH, which should be carefully considered in the application of
      glyphosate herbicide. 

PMID- 25587792
TI  - Interplay of condensation and chelation in binary and ternary Th(IV) systems.
AB  - Th(IV) readily undergoes hydrolysis and condensation in aqueous solutions to form
      polynuclear molecular species and the system becomes increasingly complicated
      when organic chelators or other metals are present in solution, leading to the
      formation of complexes with vastly different structural topologies. Five
      compounds containing binary and ternary Th(IV) complexes have been synthesized
      and structurally characterized using single-crystal X-ray diffraction, including
      Na4[Th6O2(C10O7N2H14)6].20.5H2O (Th6hedta), [Th(C9O6NH12)(H2O)(NO3)].1.5H2O
      (Th(ntp)), [Th2Al8(OH)14(H2O)12(C6O5NH8)4](NO3)6.17.5H2O (Th2Al8heidi), (C4N2H12)
      [Th2Fe2(OH)2(H2O)2(C6O7H4)2(C6O7H5)2].6H2O (Th2Fe2cit), (C4N2H12)
      [ThFe2O(H2O)3(C11O9N2H13)2].6H2O (ThFe2dhpta). Additional chemical
      characterization by infrared spectroscopy and thermogravimetric analysis provides
      information on the chelation by the organic ligands and thermal stability. These
      molecular complexes can be utilized to understand aqueous speciation in mixed
      metal solutions and also provide information regarding contaminant adsorption on
      iron(III) and aluminum(III) oxide surfaces. 

PMID- 25587791
TI  - R-loops highlight the nucleus in ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a severely debilitating neurodegenerative
      disease linked to mutations in various genes implicated in cytoplasmic RNA
      metabolism. Recent studies from genetic models have also helped reveal
      connections between various ALS-linked factors and RNA-DNA hybrid (R-loop)
      regulation. Here, we examine how such hybrid-regulatory processes are pointing to
      a key role for the nucleus in ALS. We also present a potential molecular
      mechanism in which hybrids may represent at least one of the long sought after
      missing links between different ALS genes. Our opinion is that RNA-DNA hybrids
      will play a key role in deciphering ALS and other human diseases. 

PMID- 25587793
TI  - Barriers to health-care and psychological distress among mothers living with HIV
      in Quebec (Canada).
AB  - Health-care providers play a major role in providing good quality care and in
      preventing psychological distress among mothers living with HIV (MLHIV). The
      objectives of this study are to explore the impact of health-care services and
      satisfaction with care providers on psychological distress in MLHIV. One hundred
      MLHIV were recruited from community and clinical settings in the province of
      Quebec (Canada). Prevalence estimation of clinical psychological distress and
      univariate and multivariable logistic regression models were performed to predict
      clinical psychological distress. Forty-five percent of the participants reported
      clinical psychological distress. In the multivariable regression, the following
      variables were significantly associated with psychological distress while
      controlling for sociodemographic variables: resilience, quality of communication
      with the care providers, resources, and HIV disclosure concerns. The multivariate
      results support the key role of personal, structural, and medical resources in
      understanding psychological distress among MLHIV. Interventions that can support
      the psychological health of MLHIV are discussed. 

PMID- 25587794
TI  - Psychological Stress and Immunological Modulations in Early-stage Melanoma
      Patients.
AB  - Mental stress may have a negative impact on the immune state of cancer patients,
      in whom immunologic surveillance is essential for survival. This study
      investigated the immunological response of 19 patients with early-stage melanoma
      and a matched control group undergoing the Determination Stress Test before
      surgery. Cytokine and chemokine levels and lymphocyte subpopulations were
      measured at baseline and post-stress test time-points. Following the stress test
      lower levels of interleukin (IL)-6 were observed in the melanoma group compared
      with healthy volunteers (p = 0.044). IL-10 increased significantly in the control
      group 30 min after the stress test (p = 0.002) in comparison with the melanoma
      group (p = 0.407). CCL5/Rantes decreased significantly in the melanoma group,
      whereas CD16/CD56+ natural killer cells increased in both groups, with a sharp
      decrease below baseline after stress in the melanoma group (p = 0.001). This
      pilot study shows an altered immunological response to stressors in melanoma
      patients.

PMID- 25587795
TI  - How likely is another nonmelanoma skin cancer?: better informing patients and
      clinicians.

PMID- 25587797
TI  - Overcoming the distance barrier in relation to treatment for haematology
      patients: Queensland findings.
AB  - OBJECTIVE: The aim of the present study was to document the financial and
      psychosocial impact of relocation for specialist haematology treatment in
      Queensland. METHODS: This study was a qualitative exploratory study comprising 45
      in-depth interviews with haematology patients supported by the Leukaemia
      Foundation of Queensland. RESULTS: The findings indicate that decentralisation of
      treatment is assisting haematology patients to overcome the profound difficulties
      associated with travelling to the metropolitan area for treatment. CONCLUSION:
      Fostering specialist outreach and building capacity in regional cancer centres
      are service delivery strategies that are greatly appreciated by regional, rural
      and remote haematology patients who are stressed by the many challenges
      associated with leaving home to travel distances for specialist treatment. It is
      the hope and expectation that these findings will make a contribution to
      informing future health policy and service delivery planning.

PMID- 25587796
TI  - Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria
      Syndrome fibroblasts are comparable to normal middle-age and old-age cells.
AB  - For the past several decades, research in understanding the molecular basis of
      human aging has progressed significantly with the analysis of premature aging
      syndromes. Progerin, an altered form of lamin A, has been identified as the cause
      of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a
      contributing causative factor in normal aging. However, the question of whether
      HGPS actually recapitulates the normal aging process at the cellular and
      organismal level, or simply mimics the aging phenotype is widely debated. In the
      present study we analyzed publicly available microarray datasets for fibroblasts
      undergoing cellular aging in culture, as well as fibroblasts derived from young,
      middle-age, and old-age individuals, and patients with HGPS. Using GeroScope
      pathway analysis and drug discovery platform we analyzed the activation states of
      65 major cellular signaling pathways. Our analysis reveals that signaling pathway
      activation states in cells derived from chronologically young patients with HGPS
      strongly resemble cells taken from normal middle-aged and old individuals. This
      clearly indicates that HGPS may truly represent accelerated aging, rather than
      being just a simulacrum. Our data also points to potential pathways that could be
      targeted to develop drugs and drug combinations for both HGPS and normal aging. 

PMID- 25587801
TI  - CEUS.

PMID- 25587800
TI  - A novel in vivo approach to assess radial and axial distensibility of large and
      intermediate pulmonary artery branches.
AB  - Pulmonary arteries (PAs) distend to accommodate increases in cardiac output. PA
      distensibility protects the right ventricle (RV) from excessive increases in
      pressure. Loss of PA distensibility plays a critical role in the fatal
      progression of pulmonary arterial hypertension (PAH) toward RV failure. However,
      it is unclear how PA distensibility is distributed across the generations of PA
      branches, mainly because of the lack of appropriate in vivo methods to measure
      distensibility of vessels other than the large, conduit PAs. In this study, we
      propose a novel approach to assess the distensibility of individual PA branches.
      The metric of PA distensibility we used is the slope of the stretch ratio
      pressure relationship. To measure distensibility, we combined invasive
      measurements of mean PA pressure with angiographic imaging of the PA network of
      six healthy female dogs. Stacks of 2D images of the PAs, obtained from either
      contrast enhanced magnetic resonance angiography (CE-MRA) or computed tomography
      digital subtraction angiography (CT-DSA), were used to reconstruct 3D surface
      models of the PA network, from the first bifurcation down to the sixth generation
      of branches. For each branch of the PA, we calculated radial and longitudinal
      stretch between baseline and a pressurized state obtained via acute embolization
      of the pulmonary vasculature. Our results indicated that large and intermediate
      PA branches have a radial distensibility consistently close to 2%/mmHg. Our axial
      distensibility data, albeit affected by larger variability, suggested that the
      PAs distal to the first generation may not significantly elongate in vivo,
      presumably due to spatial constraints. Results from both angiographic techniques
      were comparable to data from established phase-contrast (PC) magnetic resonance
      imaging (MRI) and ex vivo mechanical tests, which can only be used in the first
      branch generation. Our novel method can be used to characterize PA distensibility
      in PAH patients undergoing clinical right heart catheterization (RHC) in
      combination with MRI. 

PMID- 25587799
TI  - Spontaneous Gamma Activity in Schizophrenia.
AB  - IMPORTANCE: A major goal of translational neuroscience is to identify neural
      circuit abnormalities in neuropsychiatric disorders that can be studied in animal
      models to facilitate the development of new treatments. Oscillations in the gamma
      band (30-100 Hz) of the electroencephalogram have received considerable interest
      as the basic mechanisms underlying these oscillations are understood, and gamma
      abnormalities have been found in schizophrenia (SZ). Animal models of SZ based on
      hypofunction of the N-methyl-d-aspartate receptor (NMDAR) demonstrate increased
      spontaneous broadband gamma power, but this phenomenon has not been identified
      clearly in patients with SZ. OBJECTIVE: To examine spontaneous gamma power and
      its relationship to evoked gamma oscillations in the auditory cortex of patients
      with SZ. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study
      including 24 patients with chronic SZ and 24 matched healthy control participants
      at the Veterans Affairs Boston Healthcare System from January 1, 2009, through
      December 31, 2012. Electroencephalograms were obtained during auditory steady
      state stimulation at multiple frequencies (20, 30, and 40 Hz) and during a
      resting state in 18 participants in each group. MAIN OUTCOMES AND MEASURES:
      Electroencephalographic activity in the auditory cortex was estimated using
      dipole source localization. Auditory steady-state response (ASSR) measures
      included the phase-locking factor and evoked power. Spontaneous gamma power was
      measured as induced (non-phase-locked) gamma power in the ASSR data and as total
      gamma power in the resting-state data. RESULTS: The ASSR phase-locking factor was
      reduced significantly in patients with SZ compared with controls for the 40-Hz
      stimulation (mean [SD], 0.075 [0.028] vs 0.113 [0.065]; F1,46 = 6.79 [P = .012])
      but not the 20- or the 30-Hz stimulation (0.042 [0.038] vs 0.043 [0.034]; F1,46 =
      0.006 [P = .938] and 0.084 [0.040] vs 0.098 [0.050]; F1,46 = 1.605 [P = .212],
      respectively), repeating previous findings. The mean [SD] broadband-induced (30
      100 Hz) gamma power was increased in patients with SZ compared with controls
      during steady-state stimulation (6.579 [3.783] vs 3.984 [1.843]; F1,46 = 9.128 [P
      = .004]; d = 0.87) but not during rest (0.006 [0.003] vs 0.005 [0.002]; F1,34 =
      1.067 [P = .309]; d = 0.35). Induced gamma power in the left hemisphere of the
      patients with SZ during the 40-Hz stimulation was positively correlated with
      auditory hallucination symptoms (tangential, rho = 0.587 [P = .031]; radial, rho
      = 0.593 [P = .024]) and negatively correlated with the ASSR phase-locking factor
      (baseline: rho = -0.572 [P = .024]; ASSR: rho = -0.568 [P = .032]). CONCLUSIONS
      AND RELEVANCE: Spontaneous gamma activity is increased during auditory steady
      state stimulation in SZ, reflecting a disruption in the normal balance of
      excitation and inhibition. This phenomenon interacts with evoked oscillations,
      possibly contributing to the gamma ASSR deficit found in SZ. The similarity of
      increased spontaneous gamma power in SZ to the findings of increased spontaneous
      gamma power in animal models of NMDAR hypofunction suggests that spontaneous
      gamma power could serve as a biomarker for the integrity of NMDARs on parvalbumin
      expressing inhibitory interneurons in humans and in animal models of
      neuropsychiatric disorders.

PMID- 25587802
TI  - Perceived norms of premarital heterosexual relationships and sexuality among
      female college students in Tehran.
AB  - This paper describes perceptions of the societal acceptability and acceptability
      among peers of different types of premarital heterosexual relationships in Iran.
      Sources of variation in subjective norms are assessed. Results derive from a
      survey conducted in 2005 of a representative sample of 1743 female college
      students from four multidisciplinary universities in Tehran using two-stage
      random cluster sampling. An anonymous pilot-tested questionnaire was used.
      Respondents displayed remarkable heterogeneity and ambiguity concerning the
      social acceptability of premarital heterosexual friendship, dating and physical
      contact, but expressed greater certainty about the unacceptability of premarital
      sex. The majority (77.5%) reported that premarital sex was socially prohibited,
      while about one third (33.1%) were unsure about the social acceptability of
      having a boyfriend and dating before marriage. Peer norms were perceived to be
      more liberal but, nevertheless, very few peers were thought to be in favour of
      premarital intercourse. Older students, those with educated fathers and those
      studying in a mixed-sex university perceived norms to be more liberal than their
      counterparts. Access to satellite television, a major source of exposure to new
      information and values about sexuality, was a major predictor of liberal peer
      norms. It appears that a significant proportion of young people in Tehran have
      broken with tradition with regard to premarital social interaction and romantic
      friendships, but the majority still conforms to traditional cultural and
      religious values regarding abstinence before marriage. 

PMID- 25587803
TI  - Memantine plus vitamin D prevents axonal degeneration caused by lysed blood.
AB  - Intracranial hemorrhage, whether due to traumatic brain injury or ruptured
      cerebral aneurysm, is characterized by major neurological damage and a high
      mortality rate. Apart from cerebral vasospasm and mass effect, brain injury
      results from the release of unclotted blood that contacts neurons causing calcic
      stress. The combination of memantine with vitamin D, a neurosteroid hormone, may
      prevent blood neurotoxicity. Our purpose was to examine the potential protective
      effects of memantine + vitamin D against lysed or clotted blood in cortical
      neuronal cultures. We provide the first evidence that cortical axons in contact
      with lysed blood degenerate less after exposure to lysed blood in microfluidic
      neuronal cultures enriched with both memantine and vitamin D compared to control
      medium and cultures enriched with only memantine or only vitamin D. The reported
      synergistic neuroprotective effect of memantine + vitamin D, the combination
      originating an effect stronger than the sum, strongly encourages using both drugs
      following intracranial hemorrhage. 

PMID- 25587804
TI  - Effects of an eccentric training personalized by a low rate of perceived exertion
      on the maximal capacities in chronic heart failure: a randomized controlled
      trial.
AB  - BACKGROUND: The eccentric (ECC) training, in spite of its potential interest
      (slightest request of the cardiorespiratory system) compared with the concentric
      (CON) training, is not applied during the rehabilitation of the chronic heart
      failure (CHF). The main reasons are the difficulty personalizing the ECC
      exercises by avoiding the muscle complications and the lack of information
      concerning the specific effects on the maximal capacities in CHF patients. AIM:
      To compare - following a prior study on the feasibility and on the functional
      impacts - the effects on maximal capacities and tolerance in CHF of ECC training
      tailored by a low rate of perceived exertion (RPE) and those of conventionally
      tailored CON training. DESIGN: Prospective randomized comparative study. SETTING:
      A Rehabilitation Department in a University Hospital. POPULATION: CHF outpatients
      with reduced ejection fraction randomized to either ECC (N.=21) or CON training
      (N.=21). METHODS: ECC and CON training were respectively tailored by a low RPE
      (RPE between 9 and 11 on the Borg scale) and a heart rate (HR) corresponding to
      the first ventilatory threshold. Cardiopulmonary exercise test, maximal muscle
      strength tests (quadriceps, triceps surae) and 6-minute walk test were performed
      before and after training. Tolerance to training was assessed by RPE, muscle
      soreness, increase of HR, blood pressure and plasma NT-proBNP. RESULTS:
      Improvement in peak work rate was similar for both groups (+20%, P<0.01), but VO2
      peak and VO2 at the first ventilatory threshold were only increased in the CON
      group (+13.5%, P<0.01). Maximal strength of the triceps surae was increased in
      the ECC group only (+23%, P<0.01). Improvement in the walk test distance was
      similar in both groups, but the corresponding VO2 was only increased after CON
      training. Tolerance to training was good in both groups, except higher increment
      of training HR in the CON group (P<0.05). CONCLUSIONS AND CLINICAL REHABILITATION
      IMPACT: ECC training tailored by a low RPE is well tolerated in CHF patients and
      induces an improvement in maximal capacities similar to that with conventional
      CON training despite lower demands on the cardiorespiratory system, showing a
      better energetic efficiency, potentially interesting for these patients with
      reduced energetic reserve.

PMID- 25587805
TI  - Fluctuating water temperatures affect development, physiological responses and
      cause sex reversal in fathead minnows.
AB  - Natural and human activities can result in both high temporal and spatial
      variability in water temperature. Rapid temperature changes have the potential to
      dramatically affect physiological processes in aquatic organisms and, due to
      their limited mobility, fish early life stages are particularly vulnerable to
      ambient temperature fluctuations. In this study, we examined how the magnitude
      and frequency of temperature fluctuations affect survival, growth, development,
      expression of thermoresponsive genes, and gonadal differentiation in fathead
      minnows, Pimephales promelas. We exposed individuals (0 to 4 days post
      fertilization) of known genotypic sex to fluctuations of Delta4  degrees C over
      12-h, Delta8  degrees C over 12- and 24-h, and three stable temperatures (21, 25,
      and 29  degrees C) for up to 45 d. Expression of hsp70 in fish exposed to the
      highest-magnitude, highest-frequency fluctuating treatment cycled in concert with
      temperature and was upregulated initially during exposure, and may have
      contributed to temperature fluctuations having little effect on time to and size
      at hatching (whole-organism responses). This treatment also caused fish to
      undergo nondirectional sex reversal. These results indicate that hsp70 may be
      involved in mediating thermal stress from subdaily temperature fluctuations and
      that sex determination in fathead minnows can be influenced by cycling
      temperatures.

PMID- 25587806
TI  - Carcinosarcomas: tumors in transition?
AB  - Carcinosarcomas are rare, biphasic tumors that are comprised of carcinomatous and
      sarcomatous elements. While the exact mechanism by which these two phenotypes
      arise within a single tumor remains unclear, molecular evidence indicates that
      the epitheliod and spindle-cell components share a clonal origin. We propose that
      the biphasic nature of these neoplasms may represent an extreme case of
      epithelial plasticity, in which an epithelial-like cell undergoes a transition to
      a more mesenchymal phenotype. The present review will discuss both the
      histological and molecular biological evidence of the involvement of epithelial
      plasticity in driving the mixed phenotypes observed in carcinosarcomas. 

PMID- 25587807
TI  - Global health diplomacy: concepts, issues, actors, instruments, fora and cases.

PMID- 25587808
TI  - Medical and ethical concerns regarding women with hyperandrogenism and elite
      sport.

PMID- 25587809
TI  - Women with hyperandrogenism in elite sports: scientific and ethical rationales
      for regulating.
AB  - The recent implementation by some major sports-governing bodies of policies
      governing eligibility of females with hyperandrogenism to compete in women's
      sports has raised a lot of attention and is still a controversial issue. This
      short article addresses two main subjects of controversy: the existing scientific
      basis supporting performance enhancing of high blood T levels in elite female
      athletes, and the ethical rationale and considerations about these policies.
      Given the recently published data about both innate and acquired hyperandrogenic
      conditions and their prevalence in elite female sports, we claim that the high
      level of androgens are per se performance enhancing. Regulating women with
      clinical and biological hyperandrogenism is an invitation to criticism because
      biological parameters of sex are not neatly divided into only two categories in
      the real world. It is, however, the responsibility of the sports-governing bodies
      to do their best to guarantee a level playing field to all athletes. In order not
      cloud the discussions about the policies on hyperandrogenism in sports, issues of
      sports eligibility and therapeutic options should always be considered and
      explained separately, even if they may overlap. Finally, some proposals for
      refining the existing policies are made in the present article. 

PMID- 25587810
TI  - Iridium(III)-catalyzed C-7 selective C-H alkynylation of indolines at room
      temperature.
AB  - An iridium-catalyzed direct C-7 selective C-H alkynylation of indolines at room
      temperature, for the first time, has been developed via C-H bond activation.
      Furthermore, the first example of direct C-H alkynylation of carbazoles at the C1
      position is also achieved. More importantly, the resulting product can be readily
      transformed into C7-alkynylated indoles, further widening the C-7 derivatization
      of indoles and highlighting the synthetic utility of this methodology. 

PMID- 25587811
TI  - Next generation laser-based standoff spectroscopy techniques for Mars
      exploration.
AB  - In the recent Mars 2020 Rover Science Definition Team Report, the National
      Aeronautics and Space Administration (NASA) has sought the capability to detect
      and identify elements, minerals, and most importantly, biosignatures, at fine
      scales for the preparation of a retrievable cache of samples. The current Mars
      rover, the Mars Science Laboratory Curiosity, has a remote laser-induced
      breakdown spectroscopy (LIBS) instrument, a type of quantitative elemental
      analysis, called the Chemistry Camera (ChemCam) that has shown that laser-induced
      spectroscopy instruments are not only feasible for space exploration, but are
      reliable and complementary to traditional elemental analysis instruments such as
      the Alpha Particle X-Ray Spectrometer. The superb track record of ChemCam has
      paved the way for other laser-induced spectroscopy instruments, such as Raman and
      fluorescence spectroscopy. We have developed a prototype remote LIBS-Raman
      fluorescence instrument, Q-switched laser-induced time-resolved spectroscopy
      (QuaLITy), which is approximately 70 000 times more efficient at recording
      signals than a commercially available LIBS instrument. The increase in detection
      limits and sensitivity is due to our development of a directly coupled system,
      the use of an intensified charge-coupled device image detector, and a pulsed
      laser that allows for time-resolved measurements. We compare the LIBS
      capabilities of our system with an Ocean Optics spectrometer instrument at 7 m
      and 5 m distance. An increase in signal-to-noise ratio of at least an order of
      magnitude allows for greater quantitative analysis of the elements in a LIBS
      spectrum with 200-300 MUm spatial resolution at 7 m, a Raman instrument capable
      of 1 mm spatial resolution at 3 m, and bioorganic fluorescence detection at
      longer distances. Thus, the new QuaLITy instrument fulfills all of the NASA
      expectations for proposed instruments. 

PMID- 25587812
TI  - Rivaroxaban for thromboprophylaxis in a patient receiving electroconvulsive
      therapy.

PMID- 25587813
TI  - Transient expressive aphasia after bitemporal electroconvulsive therapy: a rarely
      documented reversible phenomenon.

PMID- 25587814
TI  - Pancreatoduodenectomy With Systematic Mesopancreas Dissection Using a Supracolic
      Anterior Artery-first Approach.
AB  - OBJECTIVE: To describe the details of the surgical technique of
      pancreatoduodenectomy (PD) with systematic mesopancreas dissection (SMD-PD),
      using a supracolic anterior artery-first approach. BACKGROUND: An artery-first
      approach in PD has been advocated in pancreatic cancer to judge resectability,
      clear the superior mesenteric artery margin from invasion, or reduce blood loss.
      However, the efficacy of an artery-first approach in mesopancreas dissection
      remains unclear. METHODS: This study involved 162 consecutive patients who
      underwent PD with curative intent. The patients were divided into 82 SMD-PDs and
      80 conventional PDs (CoPD) and then stratified further according to the
      dissection level, that is, level 1 was applied to 24 simple mesopancreas
      divisions for early inflow occlusion including 11 SMD-PDs, level 2 for 63 en bloc
      mesopancreas resections (26 SMD-PDs), and level 3 for 75 patients who underwent a
      hemicircumferential superior mesenteric artery plexus resection to keep the
      margin free from cancer invasion (45 SMD-PDs). The clinical and imaging results
      were collected to assess the feasibility and validity of SMD-PD with an artery
      first approach. RESULTS: Blood loss and operation duration were significantly
      less in the SMD-PD group than in the CoPD group among the total 162 patients. The
      imaging analysis showed that four fifths of pancreatic arterial branches came
      from the right dorsal aspect of the superior mesenteric artery and cancer
      abutment occurred exclusively from the same direction indicating the validity of
      an artery-first approach. CONCLUSIONS: SMD-PD using an SAA is feasible across PD
      cases, with acceptable short-term outcomes, and we propose this procedure as a
      promising option for PD.

PMID- 25587815
TI  - Enhancing mechanical properties of highly efficient polymer solar cells using
      size-tuned polymer nanoparticles.
AB  - The low mechanical durability of polymer solar cells (PSCs) has been considered
      as one of the critical hurdles for their commercialization. We described a facile
      and powerful strategy for enhancing the mechanical properties of PSCs while
      maintaining their high power conversion efficiency (PCE) by using monodispersed
      polystyrene nanoparticles (PS NPs). We prepared highly monodispersed, size
      controlled PS NPs (60, 80, and 100 nm), and used them to modify the poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) anode buffer layer
      (ABL). The PS NPs played two important roles; i.e., they served as (1) binders in
      the PEDOT:PSS films, and (2) interfacial modifiers between ABL and the active
      layer, resulting in remarkable improvement of the mechanical integrity of the
      PSCs. The addition of PS NPs enhanced the inherent mechanical toughness of the
      PEDOT:PSS ABL due to their elastic properties, allowing the modified ABL to
      tolerate higher mechanical deformations. In addition, the adhesion energy (Gc)
      between the active layer and the modified PEDOT:PSS layer was enhanced
      significantly, i.e., by a factor of more than 1.5. The Gc value has a strong
      relationship with the sizes of the PS NP, showing the greatest enhancement when
      the largest size PS NPs (100 nm) were used. In addition, PS NPs significantly
      improve the air-stability of the PSCs by suppressing moisture adsorption and
      corrosion of the electrodes. Thus, the modification of ABL with PS NPs
      effectively enhances both the mechanical and the long-term stabilities of the
      PSCs without sacrificing their PCE values, demonstrating their great potential as
      applications in flexible organic electronics. 

PMID- 25587816
TI  - Potential mental health consequences for workers in the Ebola regions of West
      Africa--a lesson for all challenging environments.

PMID- 25587817
TI  - Exhausted but not cynical: burnout in therapists working within Improving Access
      to Psychological Therapy Services.
AB  - BACKGROUND: Burnout is common in mental health professionals and has serious
      personal and professional consequences. Levels and predictors of burnout for
      therapists within "Improving Access to Psychological Therapies" (IAPT) services
      are thus far unknown. AIMS: This study investigated levels and predictors of
      three burnout dimensions--Emotional Exhaustion (EE), Depersonalisation (DP) and
      Personal Accomplishment (PA)--in IAPT therapists. METHODS: Therapists from eight
      services completed a web-based survey measuring burnout levels and hypothesised
      burnout predictors. Reponses were matched to demographic information on clients
      with whom they had completed treatment in the last 2 months. RESULTS: 116 (n)
      therapists showed comparatively high levels of EE, and relatively low levels of
      DP and PA. These were predicted by some factors from the General Burnout Model
      and by Work Involvement styles. Stressful Involvement, in particular in-sessions
      feelings of anxiety predicted EE and DP, and Healing Involvement predicted
      Personal Accomplishment. The most important predictors of therapist burnout were
      service-related, particularly work demands and autonomy, and in-session feelings.
      CONCLUSIONS: Addressing these factors in IAPT services may prevent therapist
      burnout.

PMID- 25587818
TI  - Staff views on wellbeing for themselves and for service users.
AB  - BACKGROUND: Wellbeing is an important outcome in the context of recovery from
      mental illness. The views of mental health professionals on wellbeing may
      influence their approach to supporting recovery. AIMS: This study aims to explore
      views held by mental health staff about factors influencing their own wellbeing
      and that of service users with psychosis. METHODS: Semi-structured interviews
      were conducted with 14 mental health staff in South London who had worked with
      people with psychosis. Thematic analysis was used to analyse the data and
      comparisons were made between staff views of wellbeing for themselves and service
      users. RESULTS: Staff participants held similar conceptualisations of wellbeing
      for themselves and for service users. However, they suggested a differential
      impact on wellbeing for a number of factors, such as balance, goals and
      achievement, and work. Staff employed a more deficit-based perspective on
      wellbeing for service users and a more strengths-based view for themselves.
      CONCLUSIONS: Staff stated a recovery orientation in principle, but struggled to
      focus on service user strengths in practice. A stronger emphasis in clinical
      practice on amplifying strengths to foster self-management is indicated, and
      staff may need support to achieve this emphasis, e.g. through specific
      interventions and involvement of peer support workers.

PMID- 25587819
TI  - Stigma, American military personnel and mental health care: challenges from Iraq
      and Afghanistan.
AB  - BACKGROUND: Since 2001, more than 2.5 million United States military personnel
      have been deployed for combat. Over one million have served multiple deployments.
      Combat generally involved repeated exposure to highly traumatic events. Personnel
      were also victims of military sexual trauma (MST), a major risk factor for
      psychiatric illness. Most survivors do not seek or receive mental health care.
      Stigma is one of the main barriers to that care. AIMS: To explore the impact of
      stigma on personnel with psychiatric illness, and suggest some innovative ways to
      potentially reduce stigma and improve care. METHODS: Cinahl and PubMed databases
      were searched from 2001 to 2014. RESULTS: Anonymity, the use of non-stigmatizing
      language, peer-to-peer, and stigma-reduction programs help military personnel
      receive mental health care. Technology offers the opportunity for effective and
      appropriate education and treatment. CONCLUSIONS: Although stigma is formidable,
      several innovative services are available or being developed for military victims
      of trauma. Commitment of resources for program development and further research
      to explore which interventions offer the best clinical outcomes are needed to
      increase efforts to combat stigma and ensure quality care.

PMID- 25587822
TI  - Screening of bioconstituents and in vitro cytotoxicity of Clematis gouriana
      leaves.
AB  - Clematis gouriana (Ranunculaceae), a perennial herb, is used by the local
      inhabitants of the western Himalayan region for its medicinal properties. Major
      bioconstituents of C. gouriana leaves using different solvent extracts were
      obtained and analysed. The results revealed promising contents of phenolics (from
      18.19 +/- 0.10 to 22.17 +/- 0.10 mg g(-1)) as gallic acid and flavonoids (from
      2.83 +/- 0.01 to 6.52 +/- 0.08 mg g(-1)) as quercetin equivalent in different
      extracts. Aqueous acetone extract showed higher antioxidant activity with IC50
      value of 129.11 and 25.35 MUg mL(-1) against DPPH and ABTS free radicals,
      respectively. Antioxidant yield ranged from 16.87 +/- 0.27 to 24.48 +/- 0.13 mg
      g(-1) of Trolox equivalent in different extracts as measured by the FRAP assay.
      Furthermore, ethylacetate extract exhibited strong in vitro cytotoxicity against
      Chinese hamster ovary and glioma cell lines. Proximate composition (proteins,
      fats, ash and minerals) of C. gouriana leaves was also assessed. Results
      demonstrated the potential of C. gouriana bioconstituents as nutraceuticals.

PMID- 25587824
TI  - In situ nondestructive identification of natural dyes in ancient textiles by
      reflection fourier transform mid-infrared (FT-MIR) spectroscopy.
AB  - Silk embroideries and cotton grounds of ancient Caucasian (Kaitag) textiles were
      analyzed in situ by a portable Fourier transform infrared (FT-IR) spectrometer
      equipped with a reflection module. Differently colored areas were analyzed for
      the purpose of identifying the dyes fixed on the fibers. The spectra so obtained
      were elaborated by calculating the corresponding second derivative, and a library
      search was then performed using a database including the second derivative
      spectra of a large range of historical dyes and the corresponding undyed fibers.
      The results presented here suggest that this technique, combined with the library
      search method, has a good capability of recognizing natural dyes on both types of
      ancient textile fibers, in an entirely non-destructive way. 

PMID- 25587823
TI  - Oxygen isotope fractionation in phosphates: the role of dissolved complex anions
      in isotope exchange.
AB  - Oxygen isotope fractionation factors for phosphates were calculated by means of
      the increment method. The results suggest that Ag3PO4 and BiPO4 are enriched in
      (18)O relative to AgPO4, and the three phosphates are consistently depleted in
      (18)O relative to Ba3[PO4]2; fluorapatite and chlorapatite exhibit a similar
      behaviour of oxygen isotope fractionation with consistent enrichment of (18)O
      relative to hydroxyapatite. The valence, radii and coordination of metal cations
      play a quantitative role in dictating the (18)O/(16)O partitioning in these
      phosphates of different compositions. The calculated fractionation factors for
      the Ag3PO4-H2O system are in agreement with experimental determinations derived
      from enzyme-catalysed isotope exchange between dissolved inorganic phosphate and
      water at the longest reaction durations at low temperatures. This demonstrates
      that the precipitated Ag3PO4 has completely captured the oxygen isotope
      fractionation in the dissolved inorganic phosphate. The calculated fractionation
      factors for the F/Cl-apatite-water systems are in agreement with the enzyme
      catalysed experimental fractionations for the dissolved phosphate-water system at
      the longest reaction durations but larger than fractionations derived from
      bacteria-facilitated exchange and inorganic precipitation experiments as well as
      natural observations. For the experimental calibrations of oxygen isotope
      fractionation involving the precipitation of dissolved phosphate species from
      aqueous solutions, the fractionation between precipitate and water is primarily
      dictated by the isotope equilibration between the dissolved complex anions and
      water prior to the precipitation. Therefore, the present results provide a
      quantitative means to interpret the temperature dependence of oxygen isotope
      fractionation in inorganic and biogenic phosphates.

PMID- 25587825
TI  - The number of in-out catheterisations is reduced by mobilising the postoperative
      patient with bladder needs to the toilet in the recovery room: A randomised
      clinical trial.
AB  - BACKGROUND: Many patients are diagnosed with postoperative urine retention in the
      recovery room and treated with in-out catheterisation (IOC). OBJECTIVES: We
      hypothesised that the use of IOC could be reduced by mobilising patients to the
      toilet to pass urine instead of offering a bedpan or urinal. DESIGN: A
      randomised, controlled, nonblinded study with two groups. SETTING: University
      Hospital, October 2009 to June 2012. PATIENTS: One hundred and fifty-two patients
      scheduled for surgery for cervical or lumbar disc herniation. Inclusion criteria
      were a bladder volume more than 350 ml and/or the need to pass urine in the
      recovery room. INTERVENTIONS: Participants were randomised in the recovery room
      for mobilisation to the toilet (Group I) or use of a bedpan or urinal in the bed
      (Group C). MAIN OUTCOME MEASURES: The number of IOC cases in the recovery room
      (primary outcome) and the duration of stay in the recovery room. RESULTS:
      Thirteen of 67 patients (19%) in Group I and 38 of 71 patients in Group C (54%)
      required IOC (P < 0.001). The median (IQR) durations of stay in the RR were 125
      (97 to 125) min in Group I and 157 (115 to 214) min in Group C (P = 0.006). The
      median times from arrival to first general ward mobilisation were 85 (37 to 139)
      min in Group I and 180 (118 to 245) min in Group C (P < 0.001). CONCLUSION:
      Patients were mobilised early after disc herniation intervention to permit toilet
      visits in the recovery room. This strategy decreased the number of IOCs, duration
      of stay in the recovery room and time from arrival to first mobilisation in the
      general ward.

PMID- 25587826
TI  - Evolution of ventilator settings during general anaesthesia for neurosurgery: An
      observational study in a German centre over 15 years.

PMID- 25587827
TI  - Synthesis of a highly dispersive sinapinic acid@graphene oxide (SA@GO) and its
      applications as a novel surface assisted laser desorption/ionization mass
      spectrometry for proteomics and pathogenic bacteria biosensing.
AB  - Graphene oxide (GO)-modified sinapinic acid (3,5-dimethoxy-4-hydroxycinnamic
      acid, SA) (SA@GO) was synthesized and characterized; it was then investigated as
      a new surface assisted laser desorption/ionization mass spectrometry (SALDI-MS)
      for proteomics and pathogenic bacteria biosensing. SA@GO could effectively
      decrease the time necessary for sweet spotting searching, reducing the amount of
      organic matrix and solvent and enhance the sensitivity. SA@GO shows high
      performance as a matrix alone without the need to add trifluoroacetic acid (TFA).
      However, the analysis of the intact bacteria cells shows improvement in the
      signal intensity (2-5 fold) and offers a low limit of detection. All these
      analyses could be performed with low concentrations (1-10 fmol) and tiny volumes
      (0.5-1 MUL). This study demonstrated that the exploration of new hybrid materials
      is pivotal to achieve high performance and high ionization. Because of the plane
      of GO, it assists protein-protein interactions that make it undergo softer
      ionization. 

PMID- 25587828
TI  - Synthesis of isoindolinones via a ruthenium-catalyzed cyclization of N
      substituted benzamides with allylic alcohols.
AB  - N-Substituted aromatic and heteroaromatic amides reacted with substituted allylic
      alcohols in the presence of a ruthenium catalyst, AgSbF6 and a Cu(OAc)2.H2O
      oxidant, affording 3-substituted isoindolinone derivatives with diverse
      substituents in good to excellent yields. A possible reaction mechanism involving
      a five-membered ruthenacycle intermediate was proposed and strongly supported by
      experimental evidence. 

PMID- 25587829
TI  - Physical properties of high Li-ion content N-propyl-N-methylpyrrolidinium
      bis(fluorosulfonyl)imide based ionic liquid electrolytes.
AB  - Electrolytes based on bis(fluorosulfonyl)imide (FSI) with a range of LiFSI salt
      concentrations were characterized using physical property measurements, as well
      as NMR, FT-IR and Raman spectroscopy. Different from the behavior at lower
      concentrations, the FSI electrolyte containing 1 : 1 salt to IL mole ratio showed
      less deviation from the KCl line in the Walden plot, suggesting greater ionic
      dissociation. Diffusion measurements show higher mobility of lithium ions
      compared to the other ions, which suggests that the partial conductivity of Li(+)
      is higher at this higher composition. Changes in the FT-IR and Raman peaks
      indicate that the cis-FSI conformation is preferred with increasing Li salt
      concentration. 

PMID- 25587830
TI  - Iron-doping-enhanced photoelectrochemical water splitting performance of
      nanostructured WO3: a combined experimental and theoretical study.
AB  - In this paper, we have studied Fe-doping of nanostructured tungsten trioxide
      (WO3) and its pronounced effect in promoting the photoelectrochemical (PEC) water
      splitting performance. Vertically aligned Fe-doped WO3 nanoflakes on fluorine
      doped tin oxide (FTO) were synthesized via the hydrothermal method. An X-ray
      photoelectron spectroscopy (XPS) analysis confirmed the Fe(3+) substitution at
      the W(6+) site in the prepared films. Broadened visible light absorption was
      observed in doped films, likely due to the formation of extra band states through
      doping. The Fe-doping was shown to greatly improve the PEC water splitting
      performance of WO3. More specifically, the 2 mol% Fe-doped WO3 achieved a
      photocurrent density of 0.88 mA cm(-2) at 1.23 V versus RHE, approximately 30%
      higher than that of the undoped WO3 (0.69 mA cm(-2) at 1.23 V versus RHE). This
      enhancement was attributed to the reduced band gap and the doping-enhanced charge
      carrier density as confirmed by the absorption spectra and the Mott-Schottky
      plots, respectively. Finally, first-principles density functional theory (DFT)
      calculations confirmed that the formation of oxygen vacancies was favored after
      Fe-doping, contributing to the increased charge carrier density in slightly doped
      films. 

PMID- 25587831
TI  - MS-based methods for biomarkers of Parkinson's disease: what is the future?

PMID- 25587832
TI  - Bioanalytical laboratory automation development: why should we and how could we
      collaborate?

PMID- 25587833
TI  - Metabolic profiling of epithelial ovarian cancer cell lines: evaluation of
      harvesting protocols for profiling using NMR spectroscopy.
AB  - BACKGROUND: Metabolic profiling represents a novel technology for analyzing tumor
      cells. Epithelial ovarian carcinoma has a low survival rate due to the
      development of aggressive and chemotherapy-resistant cells. A tailored and
      reliable protocol is presented for profiling of chemoresistant cells using the
      cell line SKOV3 and a multiresistant subline SKOV3R. RESULTS: Harvesting
      protocols with cold methanol or MilliQ freeze/thaw cycles were compared.
      Increased reproducibility using MilliQ was evidenced. Importantly, both
      approaches resulted in similar profiles. Compared with parental SKOV3, the SKOV3R
      cells showed a significantly different profile. CONCLUSION: The MilliQ protocol
      is preferred owing to higher reproducibility and increased sample preparation
      options. The resulting metabolic profiles summarize metabolic alterations in
      chemoresistant cells consistent with a progressed and aggressive phenotype.

PMID- 25587834
TI  - Quantitation of 25-hydroxyvitamin D2 and D3 in serum and plasma by LCMS/MS.
AB  - OBJECTIVE: We developed and validated an analytical method for quantifying 25
      hydroxyvitamin D2 (25OHD2) and 25-hydroxyvitamin D3 (25OHD3) in serum and plasma.
      METHODS: Samples, pretreated with zinc sulfate and methanol, were extracted with
      hexane. Separation was achieved via UHPLC and 25OHD quantification was
      accomplished by a triple quadrupole mass spectrometer. RESULTS: Imprecision was
      3.6-15.1%CV and bias 88.0-126.0%. Extraction efficiency was 76.5-110.5%, whereas
      the matrix effect ranged from -46.7 to -32.0%. The method was applied to
      authentic specimens. The results showed no significant difference between serum
      and plasma; strong correlation with paired values from an external laboratory;
      and analyte stability for 15 days. CONCLUSION: This method provides reliable and
      accurate measurement of 25OHD for use in clinical practice.

PMID- 25587835
TI  - Applying dried blood spot sampling with LCMS quantification in the clinical
      development phase of tasquinimod.
AB  - BACKGROUND: Tasquinimod is an orally active anticancer drug in late clinical
      development. Here we describe the development and validation of a bioanalytical
      method based upon dried blood spot analysis in combination with LCMS/MS and
      stable isotope dilution. RESULTS & DISCUSSION: The present method was validated
      for accuracy, precision, linearity, selectivity, carry-over and ruggedness. Data
      elucidating stability of tasquinimod in dried blood spots and in blood at ambient
      temperature was investigated and found adequate. Furthermore, in a clinical
      study, incurred samples reanalysis was performed, and the correlation of blood
      concentration versus plasma concentrations of tasquinimod was investigated.
      CONCLUSION: The method described here is suitable for bioanalysis of tasquinimod
      in whole blood from humans in clinical studies.

PMID- 25587836
TI  - Determination of riociguat and its major human metabolite M-1 in human plasma by
      stable-isotope dilution LCMS/MS.
AB  - BACKGROUND: Riociguat (BAY 63-2521) is an oral NO-independent as well as NO
      synergistic stimulator of soluble guanylate cyclase (sGC) for the treatment of
      pulmonary hypertension. BAY 60-4552 (M-1) is its pharmacologically active major
      metabolite. An isotope dilution LC-ESI-MS/MS method has been developed and
      validated for the simultaneous determination of riociguat and M-1 in lithium
      heparinized human plasma. RESULTS: The validated concentration range covers 0.500
      MUg/l (LLOQ) to 100 MUg/l (ULOQ) for both analytes. Interassay accuracy and
      precision (%CV) for both analytes ranged from 92.7 to 111% and from 2.61 to
      9.89%, respectively. CONCLUSION: The method proved to be selective, specific,
      sufficiently sensitive, highly reproducible and robust for the analysis of large
      numbers of samples.

PMID- 25587838
TI  - Justifying the lack of incurred sample reproducibility in a study: considerations
      and strategies.
AB  - In 2012 with the issuance of its Guideline on Bioanalytical Method Validation,
      the European Medicine Agency (EMA) made the incurred sample reproducibility (ISR)
      assessment a requirement for studies to be submitted to European authorities.
      Since then 2012, European agencies have started to issue deficiencies to
      pharmaceutical companies for lack of ISRs in studies submitted recently but
      performed prior to the issuance of the 2012 Guideline. It now becomes the
      applicant's responsibility to justify scientifically the departure from the new
      guideline even for less recent studies. This article details the different
      strategies to provide an adequate justification for the absence of ISR data in
      studies performed prior to February 2012 but submitted to European agencies after
      that date. 

PMID- 25587837
TI  - Simultaneous determination of levodopa, carbidopa, entacapone, tolcapone, 3-O
      methyldopa and dopamine in human plasma by an HPLC-MS/MS method.
AB  - BACKGROUND: In this study, we developed and validated a HPLC-MS/MS method capable
      of simultaneously determining levodopa, carbidopa, entacapone, tolcapone, 3-O
      methyldopa and dopamine in human plasma. RESULTS & METHODOLOGY: Chromatographic
      separation was achieved using a C8 column with a mobile phase consisting of a
      gradient of water and acetonitrile:methanol (90:10 v/v), both containing 0.1%
      formic acid. The developed method was selective, sensitive (LD<7.0 ng ml(-1)),
      linear (r>0.99), precise (RSD<11.3%), accurate (RE<11.8%) and free of residual
      and matrix effects. The developed method was successfully applied in plasma
      patients with Parkinson's disease using Stalevo(r). CONCLUSION: The new method
      can be used for the clinical monitoring of these substances and applied to
      adjustments in drug dosages.

PMID- 25587840
TI  - Enrichment of phosphorylated peptides and proteins by selective precipitation
      methods.
AB  - Protein phosphorylation is one of the most prominent post-translational
      modifications involved in the regulation of cellular processes. Fundamental
      understanding of biological processes requires appropriate bioanalytical methods
      for selectively enriching phosphorylated peptides and proteins. Most of the
      commonly applied enrichment approaches include chromatographic materials
      including Fe(3+)-immobilized metal-ion affinity chromatography or metal oxides.
      In the last years, the introduction of several non-chromatographic isolation
      technologies has increasingly attracted the interest of many scientists. Such
      approaches are based on the selective precipitation of phosphorylated peptides
      and proteins by applying various metal cations. The excellent performance of
      precipitation-based enrichment methods can be explained by the absence of any
      stationary phase, resin or sorbent, which usually leads to unspecific binding.
      This review provides an overview of recently published methods for the selective
      precipitation of phosphorylated peptides and proteins. 

PMID- 25587839
TI  - Recommendations for adaptation and validation of commercial kits for biomarker
      quantification in drug development.
AB  - Increasingly, commercial immunoassay kits are used to support drug discovery and
      development. Longitudinally consistent kit performance is crucial, but the degree
      to which kits and reagents are characterized by manufacturers is not
      standardized, nor are the approaches by users to adapt them and evaluate their
      performance through validation prior to use. These factors can negatively impact
      data quality. This paper offers a systematic approach to assessment, method
      adaptation and validation of commercial immunoassay kits for quantification of
      biomarkers in drug development, expanding upon previous publications and
      guidance. These recommendations aim to standardize and harmonize user practices,
      contributing to reliable biomarker data from commercial immunoassays, thus,
      enabling properly informed decisions during drug development. 

PMID- 25587841
TI  - Detection of the disease-associated form of the prion protein in biological
      samples.
AB  - Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases
      that occur in a variety of mammals. In TSEs, a chromosomally encoded protein
      (PrPC) undergoes a conformational change to the disease-associated form (PrPd).
      PrPd is capable of inducing a change in additional molecules of PrPC to the PrPd
      conformation. TSEs are inevitably fatal and cross-species transmission is known
      to occur, and there is potential for transmission via blood transfusion and organ
      transplantation in humans. Thus, there is interest in high-quality diagnostics
      for both humans and animals. This review summarizes methods of TSE detection
      currently in use in diagnostic settings and discusses recent advances in PrPd
      detection that afford substantial enhancements in sensitivity over currently
      approved methods for use in clinical settings.

PMID- 25587842
TI  - SERS-based approaches toward genetic profiling.
AB  - In the last decade surface-enhanced Raman scattering (SERS) has experienced an
      important resurgence, and as a consequence it has seen wide application in the
      biological field, especially for DNA identification. SERS-based DNA detection can
      be carried out directly and indirectly and, in the latter approach, it relies on
      the use of SERS tags, whose role is to indirectly prove the recognition and
      binding of a specific oligonucleotide sequence. Herein, the role of SERS tags is
      analyzed focusing specifically on the use of DNA identification for genetic
      profiling. 

PMID- 25587843
TI  - Additive-free thick graphene film as an anode material for flexible lithium-ion
      batteries.
AB  - This work demonstrates a simple route to develop mechanically flexible electrodes
      for Li-ion batteries (LIBs) that are usable as lightweight effective conducting
      networks for both cathodes and anodes. Removing electrochemically dead elements,
      such as binders, conducting agents and metallic current collectors, from the
      battery components will allow remarkable progress in this area. To investigate
      the feasibility of using thick, additive-free graphene films as anodes for
      flexible LIBs, we have synthesized and tested thick, additive-free, freestanding
      graphene films as anodes, first in a coin cell and further in a flexible full
      cell. As an anode material in a half cell, it showed a discharge capacity of
      about 350 mA h g(-1) and maintained nearly this capacity over 50 cycles at
      various current rates. This film was also tested as an anode material in a full
      cell with a LiCoO2 cathode and showed good electrochemical performance. Because
      the graphene-based flexible film showed good performance in half- and full coin
      cells, we used this film as a flexible anode for flexible LIBs. No conducting
      agent or binder was used in the anode side, which helped in realizing the
      flexible LIBs. Using this, we demonstrate a thin, lightweight and flexible
      lithium ion battery with good electrochemical performance in both its flat and
      bent states. 

PMID- 25587844
TI  - The role of personality traits and profiles in posttrauma comorbidity.
AB  - Many service members experience symptoms of posttraumatic stress disorder (PTSD)
      after deployment. PTSD can vary widely in its presentation and associated
      features, such as comorbid conditions. Research has shown that veterans with PTSD
      and an internalizing personality profile are more likely to experience
      internalizing comorbidity (e.g., anxiety, depression), whereas veterans with PTSD
      and an externalizing personality profile are more likely to experience
      externalizing comorbidity (e.g., substance abuse, aggression). To date, however,
      this research has been limited by a focus on diagnosable disorders and
      personality categories. In a nonclinical sample of 224 National Guard/Reserve
      service members who had served since 2001, we explored whether personality traits
      (measured continuously) moderated associations of PTSD symptom severity with the
      severity of internalizing (depression, anxiety) and externalizing (alcohol abuse,
      aggression) symptoms. Results showed that the association of PTSD with anxiety
      was stronger when extraversion was lower (corresponding to an internalizing
      personality profile). Moreover, the association of PTSD with alcohol abuse was
      stronger when extraversion was high and conscientiousness was low (corresponding
      to an externalizing personality profile). Surprisingly, this association was also
      stronger when extraversion was low and conscientiousness was high. Results offer
      additional insights into prior research on personality and comorbidity. 

PMID- 25587845
TI  - N-Halamine-modified antimicrobial polypropylene nonwoven fabrics for use against
      airborne bacteria.
AB  - Disinfecting, nonbleaching compound 1-chloro-2,2,5,5-tetramethyl-4
      imidazolidinone (MC) was uniformly coated onto polypropylene melt-blown nonwoven
      fabrics having basis-weights of 22 and 50 g/m(2) in order to impart antimicrobial
      properties via a pad-dry technique. The antimicrobial efficacies of the tested
      fabrics loaded with MC compound were evaluated against bioaerosols of
      Staphylococcus aureus and Escherichia coli O157:H7 utilizing a colony counting
      method. It was determined that both types of coated fabrics exhibited superior
      antimicrobial efficacy upon exposure to aerosol generation for 3 h. The effect of
      the coating on air permeability was found to be minimal. Samples were stable for
      a 6 month time period when they were stored in darkness. However, when the
      fabrics were exposed to fluorescent light, partial chlorine loss was observed.
      The MC-coated fabrics exhibited great potential for use in protective face masks
      and air filters to combat airborne pathogens. 

PMID- 25587846
TI  - Chronic pain: cytokines, lymphocytes and chemokines.
AB  - Chronic pain is a debilitating condition and, in most cases, difficult to treat.
      A prominent example of this is neuropathic pain. Understanding pathophysiological
      mechanisms of pain and, therefore, making this knowledge into an effective
      treatment is still a challenge to experts. Pain can now be considered as a neuro
      immune disorder, since recent data indicate critical involvement of innate and
      adaptive immune responses following injury, and this interaction plays an
      important role in the onset and perpetuation of chronic pain. The aim of this
      article is to review the relationship between immune system and chronic pain,
      especially about neuropathic pain, and focusing on cytokines, chemokines and
      lymphocytes. 

PMID- 25587847
TI  - Evolution of synthetic signaling scaffolds by recombination of modular protein
      domains.
AB  - Signaling scaffolds are proteins that interact via modular domains with multiple
      partners, regulating signaling networks in space and time and providing an ideal
      platform from which to alter signaling functions. However, to better exploit
      scaffolds for signaling engineering, it is necessary to understand the full
      extent of their modularity. We used a directed evolution approach to identify,
      from a large library of randomly shuffled protein interaction domains, variants
      capable of rescuing the signaling defect of a yeast strain in which Ste5, the
      scaffold in the mating pathway, had been deleted. After a single round of
      selection, we identified multiple synthetic scaffold variants with diverse domain
      architectures, able to mediate mating pathway activation in a pheromone-dependent
      manner. The facility with which this signaling network accommodates changes in
      scaffold architecture suggests that the mating signaling complex does not possess
      a single, precisely defined geometry into which the scaffold has to fit. These
      relaxed geometric constraints may facilitate the evolution of signaling networks,
      as well as their engineering for applications in synthetic biology. 

PMID- 25587848
TI  - Is there a gender bias in recommendations for further rehabilitation in primary
      care of patients with chronic pain after an interdisciplinary team assessment?
AB  - OBJECTIVE: To examine potential gender bias in recommendations of further
      examination and rehabilitation in primary care for patients with chronic
      musculoskeletal pain after an interdisciplinary team assessment. METHODS: The
      population consisted of consecutive patients (n = 589 women, 262 men) referred
      during a 3-year period from primary healthcare for assessment by
      interdisciplinary teams at a pain specialist rehabilitation clinic. Patient data
      were collected from the Swedish Quality Registry for Pain Rehabilitation. The
      outcome was defined as the examination or rehabilitation that was specified in
      the patient's record. RESULTS: Men had a significantly higher likelihood than
      women of being recommended physiotherapy and radiological examination, and the
      gender difference was not explained by confounding variables and covariates (age,
      marital status, ethnicity, education, working status, pain severity, pain
      interference, pain sites, anxiety and depression). There was no significant
      gender difference in recommendations to treatment by specialist physician,
      occupational therapist, psychologist or social worker. CONCLUSION: Our findings
      indicate that the interdisciplinary teams in specialist healthcare may
      discriminate against women with chronic pain when physiotherapy and radiological
      investigation are recommended. The team's choice of recommendations might be
      influenced by gendered attitudes, but this field of research needs to be studied
      further.

PMID- 25587849
TI  - Layer-by-layer polymer coated gold nanoparticles for topical delivery of imatinib
      mesylate to treat melanoma.
AB  - The aim of this study was to investigate the feasibility of using layer-by-layer
      polymer coated gold nanoparticles (AuNP) as a carrier for topical iontophoretic
      delivery of imatinib mesylate (IM). AuNP were prepared by the Turkevich method
      and were stabilized and functionalized using polyvinylpyrrolidone and
      polyethylene imine. The functionalized AuNP were then sequentially coated with
      anionic poly(styrenesulfonate) and cationic polyethylene imine and loaded with
      IM. The layer-by-layer polymer coated AuNP (LbL-AuNP) showed average particle
      size and zeta-potential of 98.5 +/- 4.3 nm and 32.3 +/- 1.3 mV respectively.
      After LbL coating of AuNP, the surface plasmon resonance wavelength shifted from
      518 to 530 nm. The loading efficiency of IM in LbL-AuNP was found to be 28.3 +/-
      2.3%, which was greatest for any small molecule loaded in AuNP. In vitro skin
      penetration studies in excised porcine ear skin showed that iontophoresis (0.47
      mA/cm(2)) application enhanced the skin penetration of IM loaded AuNP by 6.2-fold
      compared to passive application. Tape stripping studies showed that iontophoresis
      of IM loaded LbL-AuNP retained 7.8- and 4.9-fold greater IM in stratum corneum
      and viable skin respectively compared with iontophoresis of free IM. LbL-AuNP
      were taken up rapidly (15 min) by B16F10 murine melanoma cells. Furthermore, IM
      loaded LbL-AuNP significantly (p < 0.001) decreased B16F10 cell viability
      compared to free IM. We have shown for the first time that IM can be delivered by
      topical application using LbL coated gold nanoparticles to treat melanoma. 

PMID- 25587850
TI  - High-throughput profiling of nanoparticle-protein interactions by fluorescamine
      labeling.
AB  - A rapid, high throughput fluorescence assay was designed to screen interactions
      between proteins and nanoparticles. The assay employs fluorescamine, a primary
      amine specific fluorogenic dye, to label proteins. Because fluorescamine could
      specifically target the surface amines on proteins, a conformational change of
      the protein upon interaction with nanoparticles will result in a change in
      fluorescence. In the present study, the assay was applied to test the
      interactions between a selection of proteins and nanoparticles made of
      polystyrene, silica, or iron oxide. The particles were also different in their
      hydrodynamic diameter, synthesis procedure, or surface modification. Significant
      labeling differences were detected when the same protein incubated with different
      particles. Principal component analysis (PCA) on the collected fluorescence
      profiles revealed clear grouping effects of the particles based on their
      properties. The results prove that fluorescamine labeling is capable of detecting
      protein-nanoparticle interactions, and the resulting fluorescence profile is
      sensitive to differences in nanoparticle's physical properties. The assay can be
      carried out in a high-throughput manner, and is rapid with low operation cost.
      Thus, it is well suited for evaluating interactions between a larger number of
      proteins and nanoparticles. Such assessment can help to improve our understanding
      on the molecular basis that governs the biological behaviors of nanomaterials. It
      will also be useful for initial examination of the bioactivity and
      reproducibility of nanomaterials employed in biomedical fields. 

PMID- 25587851
TI  - A paradigm shift in biomass technology from complete to partial cellulose
      hydrolysis: lessons learned from nature.
AB  - A key characteristic of current biomass technology is the requirement for
      complete hydrolysis of cellulose and hemicellulose, which stems from the
      inability of microbial strains to use partially hydrolyzed cellulose, or
      cellodextrin. The complete hydrolysis paradigm has been practiced over the past 4
      decades with major enzyme companies perfecting their cellulase mix for maximal
      yield of monosaccharides, with corresponding efforts in strain development focus
      almost solely on the conversion of monosaccharides, not cellodextrin, to
      products. While still in its nascent infancy, a new paradigm requiring only
      partial hydrolysis has begun to take hold, promising a shift in the biomass
      technology at its fundamental core. The new paradigm has the potential to reduce
      the requirement for cellulase enzymes in the hydrolysis step and provides new
      strategies for metabolic engineers, synthetic biologists and alike in engineering
      fermenting organisms. Several recent publications reveal that microorganisms
      engineered to metabolize cellodextrins, rather than monomer glucose, can reap
      significant energy gains in both uptake and subsequent phosphorylation. These
      energetic benefits can in turn be directed for enhanced robustness and increased
      productivity of a bioprocess. Furthermore, the new cellodextrin metabolism endows
      the biocatalyst the ability to evade catabolite repression, a cellular regulatory
      mechanism that is hampering rapid conversion of biomass sugars to products.
      Together, the new paradigm offers significant advantages over the old and
      promises to overcome several critical barriers in biomass technology. More
      research, however, is needed to realize these promises, especially in discovery
      and engineering of cellodextrin transporters, in developing a cost-effective
      method for cellodextrin generation, and in better integration of cellodextrin
      metabolism to endogenous glycolysis. 

PMID- 25587852
TI  - Electrocatalytic activity of molybdenum disulfide nanosheets enhanced by self
      doped polyaniline for highly sensitive and synergistic determination of adenine
      and guanine.
AB  - Recently, easy, green, and low-cost liquild exfoliation of bulk materials to
      obtain thin-layered nanostructure significantly emerged. In this work, thin
      layered molybdenum disulfide (MoS2) nanosheets were fabricated through
      intercalation of self-doped polyaniline (SPAN) to layer space of bulk MoS2 by
      ultrasonic exfoliating method to effectively prevent reaggregation of MoS2
      nanosheets. The obtained hybrid showed specific surface area, a large number of
      electroactive species, and open accessible space, accompanied by rich negative
      charged and special conjugated structure, which was applied to adopt positively
      charged guanine and adenine, based on their strong pi-pi* interactions and
      electrostatic adsorption. Also, the SPAN-MoS2 interface exhibited the synergistic
      effect and good electrocatalytic activity compared with the sole SPAN or MoS2
      modified electrode. 

PMID- 25587853
TI  - Three conformers of 2-furoic acid: structure changes induced with near-IR laser
      light.
AB  - Conformers of 2-furoic acid were studied using the matrix-isolation technique
      combined with narrow-band near-IR excitations with tunable laser light. Two
      conformers of the compound were trapped from the gas phase into low-temperature
      Ar or Ne matrixes with the population ratio of nearly 1:1. The two forms differ
      from each other by 180 degrees  rotation of the carboxylic group with respect to
      the furan ring. In both structures, the OH group adopts the cis orientation, with
      its H atom directed toward the C?O bond of the O?C-O-H group. Narrow-band near-IR
      excitations of the OH stretching overtone vibrations resulted in transformation
      of one of the initially observed conformers into a third conformational
      structure. This near-IR-induced isomerization concerned rotation of the OH group
      from the initial cis orientation to the trans conformation with the hydrogen atom
      directed toward the oxygen atom of the furan ring. In the photoproduced
      conformer, the hydrogen-bond-like O-H...O interaction (between O-H and the oxygen
      atom of the furan ring) is rather weak. Nevertheless, this interaction stabilized
      the structure so that it was present in the matrix for several hours after the
      near-IR-induced generation. The spontaneous conversion of the photogenerated,
      higher-energy form back into the more stable conformer with the carboxylic group
      in cis orientation was monitored for 2-furoic acid isolated in Ar and Ne
      matrixes. The speed of this process was found to be dependent on temperature and
      on the matrix material. The experimentally determined half-life times of this
      conformational conversion occurring in the dark are t1/2 = 1390 min (Ar, 5.5 K);
      t1/2 = 630 min (Ar, 15 K); t1/2 = 240 min (Ne, 5.5 K). The three conformers of 2
      furoic acid observed in the present work were identified by comparison of their
      infrared spectra with the spectra theoretically calculated for the candidate
      structures. 

PMID- 25587854
TI  - Simple method provides resolution of albumin, lipoprotein, free fraction, and
      chylomicron to enhance the utility of protein binding assays.
AB  - Medicinal chemists have been encouraged in recent years to embrace high speed
      protein binding assays. These methods employ dialysis membranes in 96-well format
      or spin filters. Membrane-based methods do not separate lipoprotein binding from
      albumin binding and introduce interference despite membrane binding controls.
      Ultracentrifugation methods, in contrast, do not introduce interference if
      density gradients can be avoided and they resolve lipoprotein from albumin. A new
      generation of compact, fast ultracentrifuges facilitates the rapid and fully
      informative separation of plasma into albumin, albumin/fatty acid complex,
      lipoprotein, protein-free, and chylomicron fractions with no need of salt or
      sugar density gradients. We present a simple and fast ultracentrifuge method here
      for two platinum compounds and a taxane that otherwise bound irreversibly to
      dialysis membranes and which exhibited distinctive lipoprotein binding behaviors.
      This new generation of ultracentrifugation methods underscores a need to further
      discuss protein binding assessments as they relate to medicinal chemistry
      efforts. 

PMID- 25587855
TI  - Assessing Callous-Unemotional Traits in Preschool Children With Disruptive
      Behavior Problems Using Peer Reports.
AB  - The goal of this study was to examine the extent to which preschoolers with
      externalizing behavior problems (EBP) can identify behaviors indicative of
      callous-unemotional (CU) traits among their peers. Participants for this study
      included 86 preschool children (69% boys; Mage = 5.07 years) with at-risk or
      clinically elevated levels of EBP who were attending a summer treatment camp.
      Data collected from the children, their peers, and the counselors who worked at
      the summer camp examined preschoolers' social preference, likability, and
      behaviors indicative of CU. Parents and preschool teachers also reported on
      children's CU traits and severity of behavioral impairment, as well as school
      readiness. Peer nominations of CU traits showed (a) excellent factor structure as
      evidenced by clear CU items (e.g., "don't feel bad when they do something wrong")
      versus more prosocial items ("share," "cooperate"); (b) moderate construct
      validity when compared to counselor reports of the CU factor as well as preschool
      teacher reported ratings of CU traits and severity of behavioral impairment; and
      (c) good utility as evidenced by associations with peer and counselor rated
      social preference, likability, and school readiness measures as rated by both
      parents and preschool teachers. These findings indicate that as early as
      preschool, children with EBP can identify peers who engage in behaviors
      indicative of CU traits, which have significant implications for children's
      social status and overall school readiness. 

PMID- 25587858
TI  - Xanthohumol, a polyphenol chalcone present in hops, activating Nrf2 enzymes to
      confer protection against oxidative damage in PC12 cells.
AB  - Xanthohumol (2',4',4-trihydroxy-6'-methoxy-3'-prenylchalcone, Xn), a polyphenol
      chalcone from hops (Humulus lupulus), has received increasing attention due to
      its multiple pharmacological activities. As an active component in beers, its
      presence has been suggested to be linked to the epidemiological observation of
      the beneficial effect of regular beer drinking. In this work, we synthesized Xn
      with a total yield of 5.0% in seven steps and studied its neuroprotective
      function against oxidative-stress-induced neuronal cell damage in the neuronlike
      rat pheochromocytoma cell line PC12. Xn displays moderate free-radical-scavenging
      capacity in vitro. More importantly, pretreatment of PC12 cells with Xn at
      submicromolar concentrations significantly upregulates a panel of phase II
      cytoprotective genes as well as the corresponding gene products, such as
      glutathione, heme oxygenase, NAD(P)H: quinone oxidoreductase, thioredoxin, and
      thioredoxin reductase. A mechanistic study indicates that the alpha,beta
      unsaturated ketone structure in Xn and activation of the transcription factor
      Nrf2 are key determinants for the cytoprotection of Xn. Targeting the Nrf2 by Xn
      discloses a previously unrecognized mechanism underlying the biological action of
      Xn. Our results demonstrate that Xn is a novel small-molecule activator of Nrf2
      in neuronal cells and suggest that Xn might be a potential candidate for the
      prevention of neurodegenerative disorders.

PMID- 25587859
TI  - Medicare at 50--origins and evolution.

PMID- 25587860
TI  - Happy to be the new editor.

PMID- 25587856
TI  - H5N1 Virus Hemagglutinin Inhibition of cAMP-Dependent CFTR via TLR4-Mediated
      Janus Tyrosine Kinase 3 Activation Exacerbates Lung Inflammation.
AB  - The host tolerance mechanisms to avian influenza virus (H5N1) infection that
      limit tissue injury remain unknown. Emerging evidence indicates that cystic
      fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent Cl(-)
      channel, modulates airway inflammation. Janus tyrosine kinase (JAK) 3, a JAK
      family member that plays a central role in inflammatory responses, prominently
      contributes to the dysregulated innate immune response upon H5N1 attachment;
      therefore, this study aims to elucidate whether JAK3 activation induced by H5N1
      hemagglutinin (HA) inhibits cAMP-dependent CFTR channels. We performed short
      circuit current, immunohistochemistry and molecular analyses of the airway
      epithelium in Jak3(+/+) and Jak3(+/-) mice. We demonstrate that H5N1 HA
      attachment inhibits cAMP-dependent CFTR Cl(-) channels via JAK3-mediated adenylyl
      cyclase (AC) suppression, which reduces cAMP production. This inhibition leads to
      increased nuclear factor-kappa B (NF-kappaB) signaling and inflammatory
      responses. H5N1 HA is detected by TLR4 expressed on respiratory epithelial cells,
      facilitating JAK3 activation. This activation induces the interaction between
      TLR4 and Galphai protein, which blocks ACs. Our findings provide novel insight
      into the pathogenesis of acute lung injury via the inhibition of cAMP-dependent
      CFTR channels, indicating that the administration of cAMP-elevating agents and
      targeting JAK3 may activate host tolerance to infection for the management of
      influenza virus-induced fatal pneumonia. 

PMID- 25587861
TI  - Portraiture: a methodology through which success and positivity can be explored
      and reflected.
AB  - AIM: To present an overview of portraiture. BACKGROUND: Nursing is increasingly
      embracing more arts-based approaches as research methodologies. Portraiture has
      an underlying philosophy and process that enables the illumination of real people
      in real settings through the 'painting' of their stories. It is a complex
      methodology in which the researcher attempts to illuminate meaning of personal
      stories and events presented as narrative. DATA SOURCES: Interview data were
      collected from nine participants from three nursing settings. Nurses were invited
      to participate in an interview or conversation designed to elicit data to address
      the research questions; the aim was to gain insight into the nurses' common
      shared meanings and shared contemplations of their feelings about resilience.
      Criteria for inclusion in this study required that all nurse participants were
      English speaking, registered with the Nurses and Midwives Board of Western
      Australia and that each had over five years' experience in the Western Australian
      healthcare environment. This was to enable reflection on significant and ongoing
      changes within the workplace as a possible source of resilient behaviours. REVIEW
      METHODS: This is a methodological paper. DISCUSSION: Portraiture blends
      aesthetics and empiricism while drawing on features of narrative, case study,
      phenomenology and ethnography. The portraits stand as individual vignettes
      revealing recognisable themes and enabling patterns of experience to emerge from
      each topic being studied. Each portrait requires the researcher to constantly
      reflect on the participant's experiences by incorporating ethnographic
      observations, interview responses, impressionistic records, the interpretation of
      context, and the researcher's experiences and insights. It is a methodology that
      concentrates on success and positivity to immerse the reader in carefully painted
      and perceptive stories of success and positivity in times of adversity.
      CONCLUSION: This paper describes some of the hallmarks of the portraiture method,
      one of which is to portray success and positivity, and points to the relationship
      this approach may have with contemporary social science and positive psychology
      research. IMPLICATIONS FOR RESEARCH/PRACTICE: The illumination of resilience as a
      strategy to be learned and fostered in nurses in times of adversity has
      implications for managers and nursing practice. Resilience education engenders a
      more resilient workforce and has implications for nurses choosing to or being
      able to stay in nursing during times of stress and adversity.

PMID- 25587862
TI  - Reflecting on the use of photo elicitation with children.
AB  - AIM: To reflect on the use of photo elicitation as a data collection method when
      conducting research with primary school age children (nine to 11 years).
      BACKGROUND: There is recognition that children feel an affinity with the visual
      medium; as a result, visual methods can be useful when conducting research with
      children. Photo elicitation is one such method, but there has been little
      discussion of its use with primary school children within a health context. This
      paper considers the main issues that researchers should consider. DATA SOURCES:
      This paper draws on a research study conducted by the author that used an
      ethnographic approach and photo elicitation to identify the assets underpinning
      children's wellbeing. REVIEW METHODS: A reflective discussion is used to
      highlight issues relating to the use of photo elicitation to collect data from
      primary school children. DISCUSSION: Photo elicitation is not without its
      challenges: it creates additional ethical considerations, and can be more time
      consuming and expensive. However, children value the opportunity to be involved
      in research and have their opinions sought, and photo elicitation provides a
      method of collecting data that is appropriate for children's developmental and
      cognitive maturational stages. CONCLUSION: Photo elicitation can be a positive
      experience for children, and one that is not only fun and engaging, but that is
      also empowering and valuing of their contributions. IMPLICATIONS FOR
      RESEARCH/PRACTICE: Research that uses photo elicitation needs to be carefully
      planned to ensure that the study is supported appropriately. The visual process
      can offer a unique insight into children's lives that allows health professionals
      to deepen their understanding of children's experiences.

PMID- 25587857
TI  - Sirtuin 1: A Target for Kidney Diseases.
AB  - Sirtuin 1 (SIRT1) is an evolutionarily conserved NAD(+)-dependent histone
      deacetylase that is necessary for caloric restriction-related lifespan extension.
      SIRT1, as an intracellular energy sensor, detects the concentration of
      intracellular NAD(+) and uses this information to adapt cellular energy output to
      cellular energy requirements. Previous studies on SIRT1 have confirmed its
      beneficial effects on cellular immunity to oxidative stress, reduction of
      fibrosis, suppression of inflammation, inhibition of apoptosis, regulation of
      metabolism, induction of autophagy and regulation of blood pressure. All of the
      above biological processes are involved in the pathogenesis of kidney diseases.
      Therefore, the activation of SIRT1 may become a therapeutic target to improve the
      clinical outcome of kidney diseases. In this review, we give an overview of SIRT1
      and its molecular targets as well as SIRT1-modulated biological processes, with a
      particular focus on the role of SIRT1 in kidney diseases. 

PMID- 25587863
TI  - Exploring interprofessional practices in rapid response systems: a case study
      protocol.
AB  - AIM: To describe the development of a proposed case study protocol investigating
      interprofessional relationships in a rapid response system (RRS) in a
      socioculturally complex clinical environment. BACKGROUND: Suboptimal care of
      deteriorating ward patients remains a concern for many acute healthcare
      organisations. Despite the advent of RRSs, emergency response teams are not
      always used to their full potential. How and why interprofessional relationships
      influence practices associated with the care and management of ward patients at
      risk of clinical deterioration requires investigation. DATA SOURCES: Theoretical
      and empirical literature describing case study research and RRSs. Review methods
      An integrative review approach of the literature, focusing on key terms relating
      to 'case study research' and 'rapid response system', provided context and
      informed development of the study protocol. DISCUSSION: A single-site mixed
      method instrumental case study protocol was developed using methodological
      triangulation and a multi-level model to examine interprofessional relationships
      between a broad range of stakeholders. Concurrent data collection and analysis
      will occur using document review of clinical scenarios, non-participant
      observations and semi-structured interviews. CONCLUSION: Case study research is
      an effective method for investigating socioculturally complex clinical
      environments. A strength of this approach is the flexibility in the choice of
      methods, which allows the researcher to build the design most suitable for the
      subjects or phenomena being investigated. Although this flexibility may be
      considered a potential weakness, rigour can be achieved by application of the
      strategies described. IMPLICATIONS FOR RESEARCH/PRACTICE: Findings from this
      research will provide rich descriptive insights into RRS relationships and
      healthcare professional practices during day-to-day management of acute ward
      patients at risk of or experiencing clinical deterioration. Description of this
      structured case study research approach will also inform other researchers.

PMID- 25587864
TI  - The construction of context-mechanisms-outcomes in realistic evaluation.
AB  - AIM: To discuss the construction of context-mechanisms-outcomes (CMOs) developed
      as part of a realistic evaluation study of two aggression management training
      programmes. BACKGROUND: Realistic evaluation draws on theories and methods
      derived from the social sciences. It provides a distinctive account of the nature
      of programmes and how they work. Realistic evaluation is a form of evaluation
      that is driven by theory, and was based by Pawson and Tilley ( 1997 ) on the
      philosophy of critical realism. Critical realism is an important perspective in
      modern philosophy and social science, but it is largely absent in the field of
      healthcare research. REVIEW METHODS: This paper provides a critical discussion on
      the construction of CMOs as part of a realistic evaluation study. DATA SOURCES:
      This paper draws on the personal experiences of the author in using realistic
      evaluation to evaluate training in aggression management. DISCUSSION: Realistic
      evaluation stresses four key linked concepts for explaining and understanding
      programmes: 'mechanism', 'context', 'outcome pattern' and 'context-mechanisms
      outcomes (CMO) pattern configuration'. A CMO configuration is a proposition
      stating what it is about an initiative that works, for whom and in what
      circumstances. In this way, the effectiveness of the programme is understood,
      with an explanation of why the outcomes developed as they did and how the
      programme was able to react to underlying mechanisms and in what contexts.
      Therefore, a realistic evaluation researcher is not just inspecting outcomes to
      see if an initiative (implementation) works, but is analysing the outcomes to
      discover if the conjectured mechanism or context theories are confirmed. This
      analysis provides not only evidence of effectiveness, but also an explanation
      that helps to develop and improve the content and the targeting of future
      programmes. CONCLUSION: The development of CMOs requires a great deal of skill on
      the part of the researcher and requires a flexibility of approach when collecting
      and analysing the data and in understanding the topic being investigated.
      IMPLICATIONS FOR RESEARCH/PRACTICE: Applications of realistic evaluation have
      focused largely on evaluating initiatives in the field of social policy and, more
      recently, social work practice. To date, however, there have been few published
      realistic evaluation studies within nursing; therefore this study is novel in its
      use of the methodology.

PMID- 25587865
TI  - Research methods for formal consensus development.
AB  - AIM: This paper reviews three research methods for developing consensus.
      BACKGROUND: Consensus statements and guidelines are increasingly used to clarify
      and standardise practice, and inform health policy, when relevant and rigorous
      evidence is lacking. Clinicians need to evaluate the quality of practice
      guidelines to determine whether to incorporate them into clinical practice or
      reject them. Formal methods of developing consensus provide a scientific method
      that uses expert panel members to evaluate current evidence and expert opinions
      to produce consensus statements for clinical problems. DATA SOURCES: Online
      search for relevant literature was conducted in Medline and CINAHL. REVIEW
      METHODS: A literature review of consensus, consensus development and research
      methods papers published in English in peer-reviewed journals. DISCUSSION: The
      three methods of developing consensus discussed are the Delphi technique, nominal
      group technique and the consensus development conference. The techniques and
      their respective advantages are described, and examples from the literature are
      provided. The three methods are compared and a flowchart to assist researchers
      selecting an appropriate method is included. Online resources with information on
      the development and evaluation of clinical guidelines are reviewed. CONCLUSION:
      This paper will help researchers to select an appropriate research method for
      developing consensus statements and guidelines. IMPLICATIONS FOR
      RESEARCH/PRACTICE: When developing consensus guidelines for clinical practice,
      researchers should use a formal research method to ensure rigour and credibility.

PMID- 25587866
TI  - Blogs as a way to elicit feedback on research and engage stakeholders.
AB  - AIM: To reflect on the potential of blogs to enhance engagement with research,
      create a dialogue between researchers and nurses, and provide feedback to
      researchers. BACKGROUND: Blogs can create opportunities to share ideas, provide
      an arena for interaction, and rapidly and effectively initiate dialogue and
      feedback on research. DATA SOURCES: This paper draws on analysis of comments on a
      blog post about the findings of a peer-reviewed journal article. REVIEW METHODS:
      Content analysis of web blog discussion. DISCUSSION: It is unclear if the readers
      of the blog would have accessed this article any other way. Therefore, posting
      research findings on a blog can engage a new audience of nurses and provide a way
      to feed back comments and responses to researchers. This highlights the potential
      value of online forums for 'knowledge translation' and draws attention to virtual
      collegiality, which can provide a way for nurses in diverse locations to share
      their experiences and ideas, and gain support and information. CONCLUSION:
      Research findings were brought to life through the participation of blog
      commenters, who validated findings reported in the research. IMPLICATIONS FOR
      PRACTICE/RESEARCH: Given the rapid uptake of social media, it is inevitable that
      it will become an increasingly important feature of research. This paper
      demonstrates how the nexus can occur between more formal social enquiry and less
      formal engagement in critique and knowledge translation. The authors argue that
      the rapid uptake and exchange of information through social media can provide an
      indication of the social relevance of the research.

PMID- 25587867
TI  - A gift for engaging all types of patients.

PMID- 25587871
TI  - 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-promoted decomposition of
      difluorocarbene and the subsequent trifluoromethylation.
AB  - Difluorocarbene derived from various carbene precursors could be effectively
      decomposed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). This decomposition
      process was successfully applied in the subsequent trifluoromethylation of a
      variety of (hetero)aryl iodides without the addition of an external fluoride ion.
      Mechanistic investigation revealed the detailed difluorocarbene conversion
      process in which the decomposed difluorocarbene is finally transformed into a
      fluoride ion and carbon monoxide. 

PMID- 25587868
TI  - DNA Sequence Modulates Geometrical Isomerism of the trans-8,9-  Dihydro-8-(2,6
      diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-  9-hydroxy Aflatoxin B1 Adduct.
AB  - Aflatoxin B(1) (AFB(1)), a mycotoxin produced by Aspergillus flavus, is oxidized
      by cytochrome P450 enzymes to aflatoxin B(1)-8,9-epoxide, which alkylates DNA at
      N7-dG. Under basic conditions, this N7-dG adduct rearranges to yield the trans
      8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxy
      aflatoxin B(1) (AFB(1)-FAPY) adduct. The AFB(1)-FAPY adduct exhibits geometrical
      isomerism involving the formamide moiety. NMR analyses of duplex
      oligodeoxynucleotides containing the 5'-XA-3', 5'-XC-3', 5'-XT-3', and 5'-XY-3'
      sequences (X = AFB(1)-FAPY; Y = 7-deaza-dG)demonstrate that the equilibrium
      between E and Z isomers is controlled by major groove hydrogen bonding
      interactions.Structural analysis of the adduct in the 5'-XA-3' sequence indicates
      the preference of the E isomer of the formamide group,attributed to formation of
      a hydrogen bond between the formyl oxygen and the N(6) exocyclic amino group of
      the 3'-neighboradenine. While the 5'-XA-3' sequence exhibits the E isomer, the 5'
      XC-3' sequence exhibits a 7:3 E:Z ratio at equilibrium at 283K. The E isomer is
      favored by a hydrogen bond between the formyl oxygen and the N(4)-dC exocyclic
      amino group of the 3'-neighbor cytosine. The 5'-XT-3' and 5'-XY-3' sequences
      cannot form such a hydrogen bond between the formyl oxygen and the 3'-neighbor T
      or Y, respectively, and in these sequence contexts the Z isomer is favored.
      Additional equilibria between alpha and beta anomers and the potential to exhibit
      atropisomers about the C5-N(5) bond do not depend upon sequence. In each of the
      four DNA sequences, the AFB(1)-FAPY adduct maintains the beta deoxyribose
      configuration. Each of these four sequences feature the atropisomer of the AFB(1)
      moiety that is intercalated above the 5'-face of the damaged guanine. This
      enforces the Ra axialc onformation for the C5-N(5) bond.

PMID- 25587870
TI  - DNA methylation abnormalities in congenital heart disease.
AB  - Congenital heart defects represent the most common malformation at birth,
      occurring also in ~50% of individuals with Down syndrome. Congenital heart
      defects are thought to have multifactorial etiology, but the main causes are
      largely unknown. We have explored the global methylation profile of fetal heart
      DNA in comparison to blood DNA from control subjects: an absolute correlation
      with the type of tissue was detected. Pathway analysis revealed a significant
      enrichment of differential methylation at genes related to muscle contraction and
      cardiomyopathies in the developing heart DNA. We have also searched for abnormal
      methylation profiles on developing heart-tissue DNA of syndromic and non
      syndromic congenital heart defects. On average, 3 regions with aberrant
      methylation were detected per sample and 18 regions were found differentially
      methylated between groups. Several epimutations were detected in candidate genes
      involved in growth regulation, apoptosis and folate pathway. A likely pathogenic
      hypermethylation of several intragenic sites at the MSX1 gene, involved in
      outflow tract morphogenesis, was found in a fetus with isolated heart
      malformation. In addition, hypermethylation of the GATA4 gene was present in
      fetuses with Down syndrome with or without congenital heart defects, as well as
      in fetuses with isolated heart malformations. Expression deregulation of the
      abnormally methylated genes was detected. Our data indicate that epigenetic
      alterations of relevant genes are present in developing heart DNA in fetuses with
      both isolated and syndromic heart malformations. These epimutations likely
      contribute to the pathogenesis of the malformation by cis-acting effects on gene
      expression. 

PMID- 25587872
TI  - Deciphering the GPER/GPR30-agonist and antagonists interactions using molecular
      modeling studies, molecular dynamics, and docking simulations.
AB  - The G-protein coupled estrogen receptor 1 GPER/GPR30 is a transmembrane seven
      helix (7TM) receptor involved in the growth and proliferation of breast cancer.
      Due to the absence of a crystal structure of GPER/GPR30, in this work, molecular
      modeling studies have been carried out to build a three-dimensional structure,
      which was subsequently refined by molecular dynamics (MD) simulations (up to 120
      ns). Furthermore, we explored GPER/GPR30's molecular recognition properties by
      using reported agonist ligands (G1, estradiol (E2), tamoxifen, and fulvestrant)
      and the antagonist ligands (G15 and G36) in subsequent docking studies. Our
      results identified the E2 binding site on GPER/GPR30, as well as other receptor
      cavities for accepting large volume ligands, through GPER/GPR30 pi-pi,
      hydrophobic, and hydrogen bond interactions. Snapshots of the MD trajectory at 14
      and 70 ns showed almost identical binding motifs for G1 and G15. It was also
      observed that C107 interacts with the acetyl oxygen of G1 (at 14 ns) and that at
      70 ns the residue E275 interacts with the acetyl group and with the oxygen from
      the other agonist whereas the isopropyl group of G36 is oriented toward Met141,
      suggesting that both C107 and E275 could be involved in the protein activation.
      This contribution suggest that GPER1 has great structural changes which explain
      its great capacity to accept diverse ligands, and also, the same ligand could be
      recognized in different binding pose according to GPER structural conformations. 

PMID- 25587874
TI  - Duchenne muscular dystrophy gene therapy in the canine model.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease caused by
      dystrophin deficiency. Gene therapy has significantly improved the outcome of
      dystrophin-deficient mice. Yet, clinical translation has not resulted in the
      expected benefits in human patients. This translational gap is largely due to the
      insufficient modeling of DMD in mice. Specifically, mice lacking dystrophin show
      minimum dystrophic symptoms and they do not respond to the gene therapy vector in
      the same way as human patients do. Further, the size of a mouse is hundredfolds
      smaller than a boy, making it impossible to scale-up gene therapy in a mouse
      model. None of these limitations exist in the canine DMD (cDMD) model. For this
      reason, cDMD dogs have been considered a highly valuable platform to test
      experimental DMD gene therapy. Over the last three decades, a variety of gene
      therapy approaches have been evaluated in cDMD dogs using a number of non-viral
      and viral vectors. These studies have provided critical insight for the
      development of an effective gene therapy protocol in human patients. This review
      discusses the history, current status and future directions of the DMD gene
      therapy in the canine model.

PMID- 25587873
TI  - Gene expression in asthmatic airway smooth muscle: a mixed bag.
AB  - It has long been known that airway smooth muscle (ASM) contraction contributes
      significantly to the reversible airflow obstruction that defines asthma. It has
      also been postulated that phenotypic changes in ASM contribute to the airway
      hyper-responsiveness (AHR) that is a characteristic feature of asthma. Although
      there is agreement that the mass of ASM surrounding the airways is significantly
      increased in asthmatic compared with non-asthmatic airways, it is still uncertain
      whether there are quantitative or qualitative changes in the level of expression
      of the genes and proteins involved in the canonical contractile pathway in ASM
      that could account for AHR. This review will summarize past attempts at
      quantifying gene expression changes in the ASM of asthmatic lungs as well as non
      asthmatic ASM cells stimulated with various inflammatory cytokines. The lack of
      consistent findings in asthmatic samples coupled with the relative concordance of
      results from stimulated ASM cells suggests that changes to the contractility of
      ASM tissues in asthma may be dependent on the presence of an inflammatory
      environment surrounding the ASM layer. Removal of the ASM from this environment
      could explain why hypercontractility is rarely seen ex vivo. 

PMID- 25587875
TI  - Emergence of Carbapenem-Resistant Pseudomonas aeruginosa and Acinetobacter
      baumannii Clinical Isolates Collected from Some Libyan Hospitals.
AB  - The aim of the present study was to investigate the molecular mechanism of
      carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii
      clinical isolates recovered from Libyan hospitals between April 2013 and April
      2014. In total, 49 strains (24 P. aeruginosa and 25 A. baumannii) were isolated,
      including 21 P. aeruginosa and 22 A. baumannii isolates (87.75%) resistant to
      imipenem (minimum inhibitory concentrations >=16 MUg/ml). The blaVIM-2 gene was
      detected in 19 P. aeruginosa isolates. All imipenem-resistant P. aeruginosa
      isolates showed the presence of OprD mutations. Acquired OXA-carbapenemase
      encoding genes were present in all A. baumannii isolates: blaOXA-23 (n=19) and
      blaOXA-24 (n=3). Finally, a total of 13 and 17 different sequence types were
      assigned to the 21 P. aeruginosa and the 22 A. baumannii carbapenem-resistant
      isolates, respectively. This study is the first report describing imipenem
      resistant P. aeruginosa and A. baumannii isolated from patients in Libya. We
      report the first case of co-occurrence of blaVIM-2 with oprD porin loss in
      identical isolates of P. aeruginosa in Libya and demonstrate that these oprD
      mutations can be used as a tool to study the clonality in P. aeruginosa isolates.
      We also report the first identification of multidrug-resistant A. baumannii
      isolates harboring blaOXA-23-like, blaOXA-24-like, and blaOXA-48-like genes in
      Libya. 

PMID- 25587876
TI  - Modeling flight attendants' exposure to secondhand smoke in commercial aircraft:
      historical trends from 1955 to 1989.
AB  - Flight attendants were exposed to elevated levels of secondhand smoke (SHS) in
      commercial aircraft when smoking was allowed on planes. During flight attendants'
      working years, their occupational SHS exposure was influenced by various factors,
      including the prevalence of active smokers on planes, fliers' smoking behaviors,
      airplane flight load factors, and ventilation systems. These factors have likely
      changed over the past six decades and would affect SHS concentrations in
      commercial aircraft. However, changes in flight attendants' exposure to SHS have
      not been examined in the literature. This study estimates the magnitude of the
      changes and the historic trends of flight attendants' SHS exposure in U.S.
      domestic commercial aircraft by integrating historical changes of contributing
      factors. Mass balance models were developed and evaluated to estimate flight
      attendants' exposure to SHS in passenger cabins, as indicated by two commonly
      used tracers (airborne nicotine and particulate matter (PM)). Monte Carlo
      simulations integrating historical trends and distributions of influence factors
      were used to simulate 10,000 flight attendants' exposure to SHS on commercial
      flights from 1955 to 1989. These models indicate that annual mean SHS PM
      concentrations to which flight attendants were exposed in passenger cabins
      steadily decreased from approximately 265 MUg/m(3) in 1955 and 1960 to 93
      MUg/m(3) by 1989, and airborne nicotine exposure among flight attendants also
      decreased from 11.1 MUg/m(3) in 1955 to 6.5 MUg/m(3) in 1989. Using duration of
      employment as an indicator of flight attendants' cumulative occupational exposure
      to SHS in epidemiological studies would inaccurately assess their lifetime
      exposures and thus bias the relationship between the exposure and health effects.
      This historical trend should be considered in future epidemiological studies. 

PMID- 25587877
TI  - Positional quality assessment of orthophotos obtained from sensors onboard multi
      rotor UAV platforms.
AB  - In this study we explored the positional quality of orthophotos obtained by an
      unmanned aerial vehicle (UAV). A multi-rotor UAV was used to obtain images using
      a vertically mounted digital camera. The flight was processed taking into account
      the photogrammetry workflow: perform the aerial triangulation, generate a digital
      surface model, orthorectify individual images and finally obtain a mosaic image
      or final orthophoto. The UAV orthophotos were assessed with various spatial
      quality tests used by national mapping agencies (NMAs). Results showed that the
      orthophotos satisfactorily passed the spatial quality tests and are therefore a
      useful tool for NMAs in their production flowchart. 

PMID- 25587878
TI  - Dual-tree complex wavelet transform and image block residual-based multi-focus
      image fusion in visual sensor networks.
AB  - This paper presents a novel framework for the fusion of multi-focus images
      explicitly designed for visual sensor network (VSN) environments. Multi-scale
      based fusion methods can often obtain fused images with good visual effect.
      However, because of the defects of the fusion rules, it is almost impossible to
      completely avoid the loss of useful information in the thus obtained fused
      images. The proposed fusion scheme can be divided into two processes: initial
      fusion and final fusion. The initial fusion is based on a dual-tree complex
      wavelet transform (DTCWT). The Sum-Modified-Laplacian (SML)-based visual contrast
      and SML are employed to fuse the low- and high-frequency coefficients,
      respectively, and an initial composited image is obtained. In the final fusion
      process, the image block residuals technique and consistency verification are
      used to detect the focusing areas and then a decision map is obtained. The map is
      used to guide how to achieve the final fused image. The performance of the
      proposed method was extensively tested on a number of multi-focus images,
      including no-referenced images, referenced images, and images with different
      noise levels. The experimental results clearly indicate that the proposed method
      outperformed various state-of-the-art fusion methods, in terms of both subjective
      and objective evaluations, and is more suitable for VSNs. 

PMID- 25587879
TI  - Measurement of gas-liquid two-phase flow in micro-pipes by a capacitance sensor.
AB  - A capacitance measurement system is developed for the measurement of gas-liquid
      two-phase flow in glass micro-pipes with inner diameters of 3.96, 2.65 and 1.56
      mm, respectively. As a typical flow regime in a micro-pipe two-phase flow system,
      slug flow is chosen for this investigation. A capacitance sensor is designed and
      a high-resolution and high-speed capacitance measurement circuit is used to
      measure the small capacitance signals based on the differential sampling method.
      The performance and feasibility of the capacitance method are investigated and
      discussed. The capacitance signal is analyzed, which can reflect the voidage
      variation of two-phase flow. The gas slug velocity is determined through a cross
      correlation technique using two identical capacitance sensors. The simulation and
      experimental results show that the presented capacitance measurement system is
      successful. Research work also verifies that the capacitance sensor is an
      effective method for the measurement of gas liquid two-phase flow parameters in
      micro-pipes. 

PMID- 25587880
TI  - "As needed" case management across aging services in response to depression.
AB  - A lack of clarity on how and where case management for older adults is delivered
      persists, even as evidence supports its use to respond to depression. We used in
      depth interviews with managers (n = 20) and staff surveys (n = 142) from 17
      service agencies to explore the provision of case management services in adult
      day services, homecare, senior centers, and supportive housing. Limited case
      management services were found. Barriers included limited time and resources,
      especially for senior centers and supportive housing. Results revealed a concern
      about the role, feasibility, and availability of case management for older adults
      within these settings. 

PMID- 25587881
TI  - Low-dose Anti-thymocyte Globulin Inhibits Human B-cell Differentiation into
      Antibody-Secreting Cells.
AB  - Anti-thymocyte globulin (ATG) is used in the treatment of acute organ rejection.
      We studied in vitro the effect of low-dose ATG on B-cell activation and
      differentiation to antibody-secreting cells, as this may have an effect on B cell
      driven autoimmune diseases, such as pemphigus vulgaris. Immunoglobulin production
      was analysed in the supernatants of peripheral blood mononuclear cells (PBMC) and
      CD19+ B cells from healthy donors and from patients with different autoimmune
      diseases. B-cell proliferation, viability and differentiation were analysed using
      flow cytometry. Differentiation of B cells to immunoglobulin G (IgG) secreting
      cells was significantly reduced by ATG, but not by control unspecific IgG from
      non-immunized rabbits (rIgG). B-cell viability was not altered by sub-depleting
      concentrations of ATG. In contrast, B-cell proliferation was enhanced by ATG.
      When PBMC from patients with autoimmune diseases were studied, specific
      autoantibodies could be detected in 1 out of 10 patients. In this patient, who
      had pemphigus vulgaris, ATG not only decreased total IgG, but decreased also
      specific anti-desmoglein-3. In conclusion, these data suggest that ATG at low
      concentrations inhibits B-cell differentiation and function.

PMID- 25587882
TI  - Edema and telangiectasia of the chest caused by neuroendocrine carcinoma.

PMID- 25587883
TI  - Reliability of arterial spin labelling measurements of perfusion within the
      quadriceps during steady-state exercise.
AB  - Arterial spin labelling (ASL) provides a potential method to non-invasively
      determine muscle blood flow and examine the impact of interventions such as
      supplementation and training. However, it's a method with intrinsically low
      signal, leading to limitations in accuracy and temporal resolution. To examine
      these limitations, the current study measured perfusion via ASL on three
      occasions in the rectus femoris of 10 healthy adults, during light and moderate
      exercise, over three different exercise durations. For data sampled over 9 min,
      light intensity exercise gave an average perfusion of 35.0 +/- 5.1 ml/min.100g(
      1) with a coefficient of variation (COV) of 16% and single intraclass correlation
      coefficient (ICC) of 0.67. For the moderate bout, perfusion was 51.3 +/- 5.6
      ml/min.100g(-1) (COV 10%, ICC 0.82). When the same data were analyzed over 5 min
      24 s, perfusion was 37.8 +/- 11.13 (COV 30%, ICC 0.13) during light and 49.5 +/-
      8.8 ml/min.100g(-1) (COV 18%, ICC 0.52) during moderate exercise. When sampling
      was reduced to 1 min 48 s, perfusion was 41.2 +/- 13.7 (COV 33%, ICC 0.26) during
      light and 49.5 +/- 13.6 ml/min.100g(-1) (COV 28%, ICC 0.04) during moderate
      exercise. For 9 min a significant perfusion difference was found between the
      exercise intensities; however, this was not the case for sampling over 5 min 24 s
      or 1 min 48 s. Such findings illustrate the potential of ASL to non-invasively
      monitor muscle perfusion under steady-state conditions, but highlight that
      extended exercise protocols are necessary in order to generate date of sufficient
      reliability to be able to discriminate intervention dependent perfusion
      differences. 

PMID- 25587884
TI  - Spectroscopic and crystallographic investigations of novel BODIPY-derived metal
      organic frameworks.
AB  - To explore new 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-derived metal
      organic frameworks (MOFs), we employed 2,6-dicarboxyl-1,3,5,7-tetramethyl-8
      phenyl-4,4-difluoroboradiazaindacene (H2L) as a ligand to successfully synthesize
      five coordination polymers, namely, {[Zn2(L)2(bpp)].2H2O.2EtOH}n (1),
      {[Cd2(L)2(bpp)].2H2O.EtOH}n (2), {[Cd2(L)(bpe)3(NO3)2].2H2O.DMF.EtOH}n (3),
      {[Cd(L)(bpe)0.5(DMF)(H2O)]}n (4), and {[Cd(L)(bpe)0.5].1.5H2O.DMF}n (5) (bpp =
      1,3-bi(4-pyridyl)propane, bpe = 1,2-bi(4-pyridyl)ethane). Except for two 2D-layer
      coordination polymers 3 and 4, the rest samples exhibit 3D metal-organic
      frameworks with certain pore sizes, especially MOFs 1 and 5. Spectroscopic and
      crystallographic investigations demonstrate that the absorption and emission
      energies of the BODIPY chromophores are sensitive to the coordination modes.
      Moreover, in case 2, the transition metal centers coordinated with the
      dicarboxylate ligands L(2-) are capable of forming the two BODIPY units in
      coplanar arrangements (theta = 37.9 degrees ), simultaneously suppressing the
      uncommon J-dimer absorption band centered at 705 nm with a long tail into the
      near-infrared region at room temperature. On the other hand, in comparison with
      the ligand H2L, the emission of monomer-like BODIPY in case 3 is enhanced in the
      solid state by a considerably long distance between the parallel BODIPY planes
      (about 14.0 A). 

PMID- 25587886
TI  - The challenge of quality improvement in surgical care.

PMID- 25587887
TI  - [Functional differences in the microcirculatory units of the eye].
AB  - This review describes the most important regions of microcirculation within the
      eye - their architecture as well as their function. A special emphasis is put on
      the functional heterogeneity of the microvessels and their role regarding the
      specific functions localised within the different regions of the eye (e.g. oxygen
      release by the iris capillaries, production of aqueous humor within the ciliary
      processes). The microvasculature of choroidea and retina will be described in
      more detail. The precise adjustment of the blood flow to the functional needs of
      the inner retina is a very important aspect in the retinal vessels. Here, also
      pericytes can influence the vessel calibre like in the brain capillaries. Very
      important is the vascular reaction in general to states of hypoxia, especially to
      the hypoxic and radical producing states within the photoreceptors. The following
      reaction of neovascularisation will also be examined. Finally, we describe the
      metabolic situation of the ganglion cells and nerve fibers leading to and within
      the optic cup also with regard to glaucoma. 

PMID- 25587885
TI  - Linker of nucleoskeleton and cytoskeleton (LINC) complex-mediated actin-dependent
      nuclear positioning orients centrosomes in migrating myoblasts.
AB  - Myoblast migration is essential for muscle development and repair; however, the
      factors that contribute to the polarity of migrating myoblasts are relatively
      unknown. We find that randomly migrating C2C12 myoblasts orient their centrosomes
      in the direction of migration. Using wounded monolayers, we further show that
      centrosome orientation is stimulated by the serum factor lysophosphatidic acid
      (LPA) and involves the rearward movement of the nucleus while the centrosome is
      maintained at the cell centroid. The rate of nuclear movement correlated with
      that of actin retrograde flow and both cytochalasin D and blebbistatin prevented
      nuclear movement and centrosome orientation. Actin-dependent rearward nuclear
      movement in fibroblasts is mediated by assembly of nuclear membrane nesprin-2G
      and SUN2 LINC complexes into transmembrane actin-associated nuclear (TAN) lines
      anchored by A-type lamins and emerin. In C2C12 myoblasts, depletion of nesprin
      2G, SUN2 or lamin A/C prevented nuclear movement and endogenous nesprin-2G and a
      chimeric GFP-mini-nesprin-2G formed TAN lines during nuclear movement. Depleting
      nesprin-2G strongly interfered with directed cell migration and reduced the
      efficiency of myoblast fusion into multinucleated myotubes. Our results show that
      nuclear movement contributes to centrosome orientation and polarity for efficient
      migration and fusion of myoblasts. Given that mutations in the genes encoding A
      type lamins, nesprin-2 and SUN2 cause Emery-Dreifuss muscular dystrophy and
      related myopathies, our results have implications for understanding the mechanism
      of disease pathogenesis. 

PMID- 25587889
TI  - Control or non-control state: that is the question! An asynchronous visual P300
      based BCI approach.
AB  - OBJECTIVE: Brain-computer interfaces (BCI) based on event-related potentials
      (ERP) were proven to be a reliable synchronous communication method. For everyday
      life situations, however, this synchronous mode is impractical because the system
      will deliver a selection even if the user is not paying attention to the
      stimulation. So far, research into attention-aware visual ERP-BCIs (i.e.,
      asynchronous ERP-BCIs) has led to variable success. In this study, we investigate
      new approaches for detection of user engagement. APPROACH: Classifier output and
      frequency-domain features of electroencephalogram signals as well as the
      hybridization of them were used to detect the user's state. We tested their
      capabilities for state detection in different control scenarios on offline data
      from 21 healthy volunteers. MAIN RESULTS: The hybridization of classifier output
      and frequency-domain features outperformed the results of the single methods, and
      allowed building an asynchronous P300-based BCI with an average correct state
      detection accuracy of more than 95%. SIGNIFICANCE: Our results show that all
      introduced approaches for state detection in an asynchronous P300-based BCI can
      effectively avoid involuntary selections, and that the hybrid method is the most
      effective approach.

PMID- 25587890
TI  - Over reporting of congenital syphilis in Guangzhou, China.
AB  - The purpose of this study was to evaluate the rationality of congenital syphilis
      (CS) cases reported by physicians in hospitals of various levels in Guangzhou,
      China. The over-reporting rate was calculated. The results suggested that 49.1%
      (54 out of 110) of the CS cases reviewed were identified as cases that should be
      reported; 18 of the 54 CS case were confirmed CS cases and 50.9% (56 out of 110)
      were identified as over reported. Factors associated with CS case
      misclassification were analysed. To decrease the incidence of CS, antenatal care
      management and rapid plasma reagin titres should be provided and the follow up
      for children should be raised. 

PMID- 25587888
TI  - The first structure-activity relationship studies for designer receptors
      exclusively activated by designer drugs.
AB  - Over the past decade, two independent technologies have emerged and been widely
      adopted by the neuroscience community for remotely controlling neuronal activity:
      optogenetics which utilize engineered channelrhodopsin and other opsins, and
      chemogenetics which utilize engineered G protein-coupled receptors (Designer
      Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other
      orthologous ligand-receptor pairs. Using directed molecular evolution, two types
      of DREADDs derived from human muscarinic acetylcholine receptors have been
      developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits
      neuronal firing. Importantly, these DREADDs were not activated by the native
      ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO),
      a pharmacologically inert ligand. CNO has been used extensively in rodent models
      to activate DREADDs, and although CNO is not subject to significant metabolic
      transformation in mice, a small fraction of CNO is apparently metabolized to
      clozapine in humans and guinea pigs, lessening the translational potential of
      DREADDs. To effectively translate the DREADD technology, the next generation of
      DREADD agonists are needed and a thorough understanding of structure-activity
      relationships (SARs) of DREADDs is required for developing such ligands. We
      therefore conducted the first SAR studies of hM3Dq. We explored multiple regions
      of the scaffold represented by CNO, identified interesting SAR trends, and
      discovered several compounds that are very potent hM3Dq agonists but do not
      activate the native human M3 receptor (hM3). We also discovered that the approved
      drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq
      over hM3. 

PMID- 25587893
TI  - A survey of the European Venous Forum on education and training in venous surgery
      and phlebology in Europe.
AB  - AIM: Venous training in Europe is lacking a formal curriculum among various
      specialties related to management of venous diseases. We conducted a survey in
      order to have a snapshot on the actual education and training level among
      physicians practicing currently venous surgery and phlebology in Europe. METHODS:
      From April 7, 2014 to June 11, 2014 a survey was carried out using the Survey
      Monkey system, including 11 main questions covering all the domains of training
      and education in venous surgery and phlebology. The questionnaire was sent to all
      physicians included in the current mailing list of the European Venous Forum
      (EVF) and the Mediterranean League of Angiology and Vascular Surgery. Two
      questions were particularly addressed to those physicians who had attended the
      EVF hands-on workshop (HOW) at least once. RESULTS: The response rate was 24%
      (97/400) and 51.5% of them were practicing in a hospital service. Most responders
      were vascular surgeons (67.7%), followed by angiologists (19.4%). Only half of
      the responders felt as being competent to manage the whole spectrum of venous
      diseases successfully after completion of their training, while a few were able
      to perform endovenous ablations and even less more advanced venous interventions.
      Formal training in Duplex ultrasound was undertaken only in 55.2%. The majority
      suggested that a venous training program should be a separate part of their
      specialty rotation and should be organized at a national or European level, or
      even by a specific scientific society. Over 95% of those physicians who already
      participated in the EVF HOW considered the knowledge they acquired there as
      useful for their practice. CONCLUSION: There is currently an important need for
      more specialized venous training for all physicians involved in the diagnosis and
      management of venous diseases. Therefore all local, national and international
      initiatives should be encouraged to improve education in this field.

PMID- 25587892
TI  - Telemedicine: interventional decentralised blood pressure telemonitoring
      (idTBPM).
AB  - Telemedicine comprises different methods of bridging a spatial distance between
      doctor, medical and care services and patients. These include mere data
      transmissions as well as alarm functionalities, consultations and therapy
      recommendations. A special form of telemedicine application is the interventional
      decentralised telemonitoring (idTM). Here the patient-practitioner relationship
      forms the basis for therapy control and optimisation using telemetrical medical
      data. To identify areas of indication of idTM, a detailed definition of
      transferred parameters, alarm conditions and intervention algorithms is required
      as a well as cost efficiency and feasibility studies. The quality of the
      telemedical application is determined by the medical quality of the derived
      actions. 

PMID- 25587891
TI  - Design of a pulsatile flow facility to evaluate thrombogenic potential of
      implantable cardiac devices.
AB  - Due to expensive nature of clinical trials, implantable cardiac devices should
      first be extensively characterized in vitro. Prosthetic heart valves (PHVs), an
      important class of these devices, have been shown to be associated with
      thromboembolic complications. Although various in vitro systems have been
      designed to quantify blood-cell damage and platelet activation caused by
      nonphysiological hemodynamic shear stresses in these PHVs, very few systems
      attempt to characterize both blood damage and fluid dynamics aspects of PHVs in
      the same test system. Various numerical modeling methodologies are also evolving
      to simulate the structural mechanics, fluid mechanics, and blood damage aspects
      of these devices. This article presents a completely hemocompatible small-volume
      test-platform that can be used for thrombogenicity studies and experimental fluid
      mechanics characterization. Using a programmable piston pump to drive freshly
      drawn human blood inside a cylindrical column, the presented system can simulate
      various physiological and pathophysiological conditions in testing PHVs. The
      system includes a modular device-mounting chamber, and in this presented case, a
      23 mm St. Jude Medical (SJM) Regents(r) mechanical heart valve (MHV) in aortic
      position was used as the test device. The system was validated for its capability
      to quantify blood damage by measuring blood damage induced by the tester itself
      (using freshly drawn whole human blood). Blood damage levels were ascertained
      through clinically relevant assays on human blood while fluid dynamics were
      characterized using time-resolved particle image velocimetry (PIV) using a blood
      mimicking fluid. Blood damage induced by the tester itself, assessed through
      Thrombin-anti-Thrombin (TAT), Prothrombin factor 1.2 (PF1.2), and hemolysis
      (Drabkins assay), was within clinically accepted levels. The hydrodynamic
      performance of the tester showed consistent, repeatable physiological pressure
      and flow conditions. In addition, the system contains proximity sensors to
      accurately capture leaflet motion during the entire cardiac cycle. The PIV
      results showed skewing of the leakage jet, caused by the asymmetric closing of
      the two leaflets. All these results are critical to characterizing the blood
      damage and fluid dynamics characteristics of the SJM Regents(r) MHV, proving the
      utility of this tester as a precise system for assessing the hemodynamics and
      thrombogenicity for various PHVs. 

PMID- 25587894
TI  - 'Even though it's a small checkbox, it's a big deal': stresses and strains of
      managing sexual identity(s) on Facebook.
AB  - Facebook offers a socialisation context in which young people from ethnic, gender
      and sexual minorities must continually manage the potential for prejudice and
      discrimination in the form of homophobia and racism. In-depth interviews were
      conducted with eight young women, aged 16-19 years, who self-identified as queer
      and as women of colour. A detailed analysis of these interviews--focusing in
      particular on how young people described navigating expectations of rejection
      from family and friends--offered insight into the psychological and health
      consequences associated with managing sexual identity(s) while online. The
      'closet' ultimately takes on new meaning in this virtual space: participants
      described trying to develop social relationships within Facebook, which demands
      sharing one's thoughts, behaviours and ideas, while also hiding and silencing
      their emerging sexuality. In this 'virtual closet', tempering self-presentation
      to offset social exclusion has become a continuous, yet personally treacherous,
      activity during the daily practice of using Facebook.

PMID- 25587895
TI  - Keratin-chitosan membranes as scaffold for tissue engineering of human cornea.
AB  - PURPOSE: To study the attachment and growth of human corneal cells on keratin
      chitosan membranes. The end goal is to develop a bioengineered cornea based on
      this material. METHODS: Keratin-chitosan membranes were prepared as previously
      described by Tanabe et al., 2002. Briefly, 7.15 mg/cm2 of keratin dialysate was
      mixed with 10 wt% chitosan solution and 20 wt% glycerol. The solution was cast
      into a silicone mold and dried at 50oC for 36 hours. Eyes were attained from a
      local eye bank after penetrant-keratoplastic surgery. Human epithelial, stromal
      and endothelial cells were obtained of the limbal, stromal and endothelial
      regions. Cells were cultured on keratin-chitosan membranes, as well as on plastic
      dishes as controls. When cultured cells reached confluence, they were fixed,
      incubated with primary antibodies (E-cadherin, cytokeratin high molecular weight
      (CK), vimentin and Na+/K+ ATPase) and visualized by indirect immunocytochemistry.
      RESULTS: Epithelial, stromal and endothelial cells were able to attach and grow
      on keratin-chitosan membranes. All the cells maintained their morphology and
      cellular markers, both in the membrane and on the culture plate. Epithelial cells
      stained positively for CK and E-cadherin. A positive vimentin stain was observed
      in all stromal cells, while endothelial cells were positive for vimentin and
      Na+/K+ ATPase, but negative for E-cadherin. CONCLUSIONS: Keratin-chitosan
      membranes have been shown to be a good scaffold for culturing epithelial, stromal
      and endothelial corneal cells; therefore, future applications of keratin-chitosan
      membranes may be developed for reconstruction of the cornea.

PMID- 25587896
TI  - Combining agent-based modeling and life cycle assessment for the evaluation of
      mobility policies.
AB  - This article presents agent-based modeling (ABM) as a novel approach for
      consequential life cycle assessment (C-LCA) of large scale policies, more
      specifically mobility-related policies. The approach is validated at the
      Luxembourgish level (as a first case study). The agent-based model simulates the
      car market (sales, use, and dismantling) of the population of users in the period
      2013-2020, following the implementation of different mobility policies and
      available electric vehicles. The resulting changes in the car fleet composition
      as well as the hourly uses of the vehicles are then used to derive consistent LCA
      results, representing the consequences of the policies. Policies will have
      significant environmental consequences: when using ReCiPe2008, we observe a
      decrease of global warming, fossil depletion, acidification, ozone depletion, and
      photochemical ozone formation and an increase of metal depletion, ionizing
      radiations, marine eutrophication, and particulate matter formation. The study
      clearly shows that the extrapolation of LCA results for the circulating fleet at
      national scale following the introduction of the policies from the LCAs of single
      vehicles by simple up-scaling (using hypothetical deployment scenarios) would be
      flawed. The inventory has to be directly conducted at full scale and to this aim,
      ABM is indeed a promising approach, as it allows identifying and quantifying
      emerging effects while modeling the Life Cycle Inventory of vehicles at
      microscale through the concept of agents.

PMID- 25587897
TI  - Detailed phenotypic and molecular analyses of genetically modified mice generated
      by CRISPR-Cas9-mediated editing.
AB  - The bacterial CRISPR-Cas9 system has been adapted for use as a genome editing
      tool. While several recent reports have indicated that successful genome editing
      of mice can be achieved, detailed phenotypic and molecular analyses of the mutant
      animals are limited. Following pronuclear micro-injection of fertilized eggs with
      either wild-type Cas9 or the nickase mutant (D10A) and single or paired guide RNA
      (sgRNA) for targeting of the tyrosinase (Tyr) gene, we assessed genome editing in
      mice using rapid phenotypic readouts (eye and coat color). Mutant mice with
      insertions or deletions (indels) in Tyr were efficiently generated without
      detectable off-target cleavage events. Gene correction of a single nucleotide by
      homologous recombination (HR) could only occur when the sgRNA recognition sites
      in the donor DNA were modified. Gene repair did not occur if the donor DNA was
      not modified because Cas9 catalytic activity was completely inhibited. Our
      results indicate that allelic mosaicism can occur following -Cas9-mediated
      editing in mice and appears to correlate with sgRNA cleavage efficiency at the
      single-cell stage. We also show that larger than expected deletions may be
      overlooked based on the screening strategy employed. An unbiased analysis of all
      the deleted nucleotides in our experiments revealed that the highest frequencies
      of nucleotide deletions were clustered around the predicted Cas9 cleavage sites,
      with slightly broader distributions than expected. Finally, additional analysis
      of founder mice and their offspring indicate that their general health,
      fertility, and the transmission of genetic changes were not compromised. These
      results provide the foundation to interpret and predict the diverse outcomes
      following CRISPR-Cas9-mediated genome editing experiments in mice. 

PMID- 25587899
TI  - Transcription activator-like effector nuclease (TALEN)-mediated CLYBL targeting
      enables enhanced transgene expression and one-step generation of dual reporter
      human induced pluripotent stem cell (iPSC) and neural stem cell (NSC) lines.
AB  - Targeted genome engineering to robustly express transgenes is an essential
      methodology for stem cell-based research and therapy. Although designer nucleases
      have been used to drastically enhance gene editing efficiency, targeted addition
      and stable expression of transgenes to date is limited at single gene/locus and
      mostly PPP1R12C/AAVS1 in human stem cells. Here we constructed transcription
      activator-like effector nucleases (TALENs) targeting the safe-harbor like gene
      CLYBL to mediate reporter gene integration at 38%-58% efficiency, and used both
      AAVS1-TALENs and CLYBL-TALENs to simultaneously knock-in multiple reporter genes
      at dual safe-harbor loci in human induced pluripotent stem cells (iPSCs) and
      neural stem cells (NSCs). The CLYBL-TALEN engineered cell lines maintained robust
      reporter expression during self-renewal and differentiation, and revealed that
      CLYBL targeting resulted in stronger transgene expression and less perturbation
      on local gene expression than PPP1R12C/AAVS1. TALEN-mediated CLYBL engineering
      provides improved transgene expression and options for multiple genetic
      modification in human stem cells. 

PMID- 25587898
TI  - Prevention of herpes simplex virus induced stromal keratitis by a glycoprotein B
      specific monoclonal antibody.
AB  - The increasing incidence of acyclovir (ACV) and multidrug-resistant strains in
      patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis
      (HSK) is a major health problem in industrialized countries and often results in
      blindness. To overcome this obstacle, we have previously developed an HSV-gB
      specific monoclonal antibody (mAb 2c) that proved to be highly protective in
      immunodeficient NOD/SCID-mice towards genital infections. In the present study,
      we examined the effectivity of mAb 2c in preventing the immunopathological
      disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with
      HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either
      systemically or topically treated with mAb 2c. Systemic treatment was performed
      by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure
      prophylaxis) or 24, 40, and 56 hours after infection (post-exposure
      immunotherapy). Topical treatment was performed by periodical inoculations (5
      times per day) of antibody-containing eye drops as control, starting at 24 h post
      infection. Systemic antibody treatment markedly reduced viral loads at the site
      of infection and completely protected mice from developing HSK. The
      administration of the antiviral antibody prior or post infection was equally
      effective. Topical treatment had no improving effect on the severity of HSK. In
      conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for
      the treatment of corneal HSV-infections and for prevention of HSK and blindness.
      Moreover, the humanized counterpart (mAb hu2c) was equally effective in
      protecting mice from HSV-induced HSK when compared to the parental mouse
      antibody. These results warrant the future development of this antibody as a
      novel approach for the treatment of corneal HSV-infections in humans. 

PMID- 25587901
TI  - Action control bridges the planning-behaviour gap: a longitudinal study on
      physical exercise in young adults.
AB  - OBJECTIVES: Maintaining physical exercise levels may not only require motivation
      and planning but also action control which is supposed to mediate between
      planning and exercise. DESIGN: Behavioural intention, action planning, coping
      planning and past behaviour were assessed at baseline, and action control and
      concurrent exercise were measured one month later in 497 young adults. METHOD:
      Three nested structural models were specified to examine different mediation
      mechanisms. One model reflected the intention-planning-behaviour chain, the other
      one focused on the intention-action control-behaviour chain and the third model
      comprised the full sequence. RESULTS: Indirect effects from intentions on
      exercise involved either planning or action control as mediating variables. In
      Model 3, all three constructs (action planning, coping planning and action
      control) were sequential mediators between intentions and later physical exercise
      levels. Action and coping planning were not directly but indirectly related to
      exercise via action control. CONCLUSIONS: Findings support the sequential
      mediation for planning and action control as antecedents of physical exercise.
      Action control is needed for exercise, because planning in itself is not always
      sufficient. Maintaining exercise levels may be attributed to effective self
      regulatory strategies such as action control in combination with planning.

PMID- 25587900
TI  - A behaviorally-explicit approach for delivering vaccine baits to mesopredators to
      control epizootics in fragmented landscapes.
AB  - Despite the widespread use of aerial baiting to manage epizootics among free
      ranging populations, particularly in rabies management, bait acceptance and
      seroconversion rates often are lower than required to eliminate spread of
      disease. Our objectives in this study, therefore, were to evaluate the
      performance of stratified bait distribution models derived from resource
      selection functions (RSF) on uptake of placebo rabies baits by raccoons (Procyon
      lotor) and Virginia opossums (Didelphis virginiana), as well as the probability
      of bait uptake as a function of proximity to bait distribution areas in
      fragmented agricultural ecosystems. Among 478 raccoons and 108 opossums evaluated
      for presence of Rhodamine B (RB) across 8 sites, only 26% of raccoons and 20% of
      opossums exhibited marking consistent with bait consumption 14-24 days post
      baiting. The effective area treated, based on 90% kernel density estimators of
      marked individuals, ranged from 99-240 ha larger than bait distribution zones,
      with RB marked individuals captured up to 753 m beyond the bait zone. Despite
      incorporation of RSF data into bait distribution models, no differences in uptake
      rates were observed between treatment and control sites. These data likely
      reflect the underlying constraints imposed by the loss and fragmentation of
      habitat on animal movement in heterogeneous landscapes, forcing individuals to
      optimize movements at coarse (i.e., patch-level) rather than fine spatial scales
      in highly fragmented environments. Our data also confirm that the probability of
      bait acceptance decreases with increasing distance from bait zone interiors, even
      within the zone itself. Thus, although bait acceptance was confirmed beyond bait
      zone boundaries, the proportion of vaccinated individuals may comprise a small
      minority of the population at increasing distances from baiting interiors. These
      data suggest focal baiting creates a buffered area of treated individuals around
      bait zones or bait stations, but repeated treatments may be needed to achieve
      sufficient uptake to eradicate disease.

PMID- 25587902
TI  - Transforming growth factor beta1 and aldosterone.
AB  - PURPOSE OF REVIEW: It is well established that blocking the renin-angiotensin
      aldosterone system (RAAS) is effective for the treatment of cardiovascular and
      renal complications in hypertension and diabetes mellitus. Although the induction
      of transforming growth factor beta1 (TGFbeta1) by components of the RAAS mediates
      the hypertrophic and fibrogenic changes in cardiovascular-renal complications, it
      is still controversial as to whether TGFbeta1 can be a target to prevent such
      complications. Here, we review recent findings on the role of TGFbeta1 in fluid
      homeostasis, focusing on the relationship with aldosterone. RECENT FINDINGS:
      TGFbeta1 suppresses the adrenal production of aldosterone and renal tubular
      sodium reabsorption. We have generated mice with TGFbeta1 mRNA expression graded
      in five steps, from 10 to 300% of normal, and found that blood pressure and
      plasma volume are negatively regulated by TGFbeta1. Notably, the 10% hypomorph
      exhibits primary aldosteronism and sodium and water retention due to markedly
      impaired urinary excretion of water and electrolytes. SUMMARY: These results
      identify TGFbeta signalling as an important counterregulatory system against
      aldosterone. Understanding the molecular mechanisms for the suppressive effects
      of TGFbeta1 on adrenocortical and renal function may further our understanding of
      primary aldosteronism, as well as assist in the development of novel therapeutic
      strategies for hypertension.

PMID- 25587904
TI  - Hydrogen sulfide: role in vascular physiology and pathology.
AB  - PURPOSE OF REVIEW: Hydrogen sulfide (H2S), a colorless gas that is endogenously
      generated in mammals from cysteine, has important biological functions. Within
      the vasculature it regulates vessel tone and outgrowth of new vessels. This
      review summarizes recent literature on H2S signaling in the vasculature and its
      therapeutic potential in vascular disorders RECENT FINDINGS: H2S is able to
      induce vasorelaxation via ATP-sensitive potassium channels in vascular smooth
      muscle cells. Large-conductance calcium-dependent K+-channels and Kv7 voltage
      gated K+-channels are also involved in H2S signaling. Vascular endothelial growth
      factor is the key downstream mediator that is involved in H2S induced
      angiogenesis. By having both direct effects on its receptor and increasing the
      bioavailability of vascular endothelial growth factor, H2S is proangiogenic. H2S
      based therapies in vascular diseases are an expanding area of research. The
      applications of several compounds, such as natural donors and synthetic slow
      release compounds, have been extensively studied in vascular diseases such as
      hypertension, ischemia-reperfusion disorders and preeclampsia. SUMMARY: H2S has a
      key role in vascular homeostasis during physiology and in pathological states.
      H2S-based therapies may have a role in several vascular diseases.

PMID- 25587903
TI  - Molecular mechanisms regulating vascular tone by peroxisome proliferator
      activated receptor gamma.
AB  - PURPOSE OF REVIEW: This review summarizes recent findings on the regulation of
      vascular tone by the nuclear receptor transcription factor, peroxisome
      proliferator activated receptor (PPAR) gamma. Much of the recent work utilizes
      genetic tools to interrogate the significance of PPARgamma in endothelial and
      smooth muscle cells and novel PPARgamma target genes have been identified. RECENT
      FINDINGS: Endothelial PPARgamma prevents inflammation and oxidative stress, while
      promoting vasodilation by controlling the regulation of NADPH oxidase, catalase
      and superoxide dismutase gene expression. Moreover, the protective functions of
      endothelial PPARgamma appear more prominent during disease conditions. Novel
      findings also suggest a role for endothelial PPARgamma as a mediator of whole
      body metabolism. In smooth muscle cells, PPARgamma regulates vascular tone by
      targeting genes involved with contraction and relaxation signaling cascades, some
      of which is via transcriptional activation, and some through novel mechanisms
      regulating protein turnover. Furthermore, aberrant changes in renin-angiotensin
      system components and exacerbated responses to angiotensin II induced vascular
      dysfunction are observed when PPARgamma function is lost in smooth muscle cells.
      SUMMARY: With these recent advances based partially on lessons from patients with
      PPARgamma mutants, we conclude that vascular PPARgamma is protective and plays an
      important role in the regulation of vascular tone.

PMID- 25587908
TI  - Multivariate normative comparison, a novel method for more reliably detecting
      cognitive impairment in HIV infection.
AB  - OBJECTIVE: The objective of this study is to assess whether multivariate
      normative comparison (MNC) improves detection of HIV-1-associated neurocognitive
      disorder (HAND) as compared with Frascati and Gisslen criteria. METHODS: One
      hundred and three HIV-1-infected men with suppressed viremia on combination
      antiretroviral therapy (cART) for at least 12 months and 74 HIV-uninfected male
      controls (comparable regarding age, ethnicity, sexual orientation, premorbid
      intelligence and educational level), aged at least 45 years, underwent
      neuropsychological assessment covering six cognitive domains (fluency, attention,
      information processing speed, executive function, memory, and motor function).
      Frascati and Gisslen criteria were applied to detect HAND. Next, MNC was
      performed to compare the cognitive scores of each HIV-positive individual against
      the cognitive scores of the control group. RESULTS: HIV-infected men showed
      significantly worse performance on the cognitive domains of attention,
      information processing speed and executive function compared with HIV-uninfected
      controls. HAND by Frascati criteria was highly prevalent in HIV-infected [48%;
      95% confidence interval (95% CI) 38-58] but nearly equally so in HIV-uninfected
      men (36%; 95% CI 26-48), confirming the low specificity of this method. Applying
      Gisslen criteria, HAND-prevalence was reduced to 5% (95% CI 1-9) in HIV-infected
      men and to 1% (95% CI 1-3) among HIV-uninfected controls, indicating better
      specificity but reduced sensitivity. MNC identified cognitive impairment in 17%
      (95% CI 10-24) of HIV-infected men and in 5% (95% CI 0-10) of the control group
      (P = 0.02, one-tailed), showing an optimal balance between sensitivity and
      specificity. CONCLUSION: Prevalence of cognitive impairment in HIV-1-infected men
      with suppressed viremia on cART estimated by MNC was much higher than that
      estimated by Gisslen criteria, while the false positive rate was greatly reduced
      compared with the Frascati criteria. VIDEO ABSTRACT: :

PMID- 25587910
TI  - Horseradish peroxidase-immobilized magnetic mesoporous silica nanoparticles as a
      potential candidate to eliminate intracellular reactive oxygen species.
AB  - Horseradish peroxidase-immobilized magnetic mesoporous silica nanoparticles
      (MMSNs-HRP) have been synthesized by a NHS/EDC coupling between the amino groups
      of horseradish peroxidase (HRP) and the carboxyl groups on the MMSNs surface. It
      is found that the immobilized HRP on MMSNs still retain high activity and the
      MMSNs-HRP can eliminate the reactive oxygen species (ROS) in Chinese hamster
      ovary (CHO) cells induced by the addition of H2O2 aqueous solution. Further, the
      fluorescent MMSN-HRP-CD nanoparticles have been prepared by attaching
      biocompatible, fluorescent carbon dots (CDs) to MMSNs-HRP. We have also
      investigated the effect of an applied magnetic field on cellular uptake of MMSNs
      HRP-CDs and found that the internalization of MMSNs-HRP-CDs by CHO cells could be
      enhanced within 2 hours under the magnetic field. This work provides us with a
      novel and efficient method to eliminate ROS in living cells by using HRP
      immobilized nanoparticles. 

PMID- 25587909
TI  - HIV-associated mucosal gene expression: region-specific alterations.
AB  - OBJECTIVE: Despite the use of HAART to control HIV, systemic immune activation
      and inflammation persists with the consequence of developing serious non-AIDS
      events. The mechanisms that contribute to persistent systemic immune activation
      have not been well defined. The intestine is the major source of "sterile"
      inflammation and plays a critical role in immune function; thus, we sought to
      determine whether intestinal gene expression was altered in virally controlled
      HIV-infected individuals. DESIGN AND METHODS: Gene expression was compared in
      biopsy samples collected from HIV-uninfected and HIV-infected individuals from
      the ileum, right colon (ascending colon), and left colon (sigmoid). Affymetrix
      gene arrays were performed on tissues and pathway analyses were conducted. Gene
      expression was correlated with systemic markers of intestinal barrier dysfunction
      and inflammation and intestinal microbiota composition. RESULTS: Genes involved
      in cellular immune response, cytokine signaling, pathogen-influenced signaling,
      humoral immune response, apoptosis, intracellular and second messenger signaling,
      cancer, organismal growth and development, and proliferation and development were
      upregulated in the intestine of HIV-infected individuals with differences
      observed in the ileum, right, and left colon. Gene expression in the ileum
      primarily correlated with systemic markers of inflammation (e.g., IL7R, IL2, and
      TLR2 with serum TNF) whereas expression in the colon correlated with the
      microbiota community (e.g., IFNG, IL1B, and CD3G with Bacteroides). CONCLUSION:
      These data demonstrate persistent, proinflammatory changes in the intestinal
      mucosa of virally suppressed HIV-infected individuals. These changes in
      intestinal gene expression may be the consequence of or contribute to barrier
      dysfunction and intestinal dysbiosis observed in HIV.

PMID- 25587911
TI  - Influence of the -CH2X substituent on the regioselectivity of intramolecular meta
      photocycloaddition reactions.
AB  - In studies related to the synthesis of the bicyclo[3.2.1]octane core of enterocin
      by an intramolecular meta-photocycloaddition, it was found that the
      regioselectivity of the reaction depends strongly on the substituent -CH2X in the
      ortho-position to the tether. Electropositive groups X (X = H, Me, TMS, TES) gave
      preferentially the linear isomer (regioisomeric ratio = 87/13 to >95/5), whereas
      electronegative substituents (X = OH, OAc, F) showed a clear preference for the
      angular isomer (regioisomeric ratio = 75/25 to >95/5). The silylated and
      fluorinated products were obtained as single isomers in moderate yield. 

PMID- 25587912
TI  - Editorial.

PMID- 25587905
TI  - Pharmacotherapy of glaucoma.
AB  - Glaucoma is a group of diseases involving the optic nerve and associated
      structures, which is characterized by progressive visual field loss and typical
      changes of the optic nerve head (ONH). The only known treatment of the disease is
      reduction of intraocular pressure (IOP), which has been shown to reduce glaucoma
      progression in a variety of large-scale clinical trials. Nowadays, a relatively
      wide array of topical antiglaucoma drugs is available, including prostaglandin
      analogues, carbonic anhydrase inhibitors, beta-receptor antagonists, adrenergic
      agonists, and parasympathomimetics. In clinical routine, this allows for
      individualized treatment taking risk factors, efficacy, and safety into account.
      A major challenge is related to adherence to therapy. Sustained release devices
      may help minimize this problem but are not yet available for clinical routine
      use. Another hope arises from non-IOP-related treatment concepts. In recent
      years, much knowledge has been gained regarding the molecular mechanisms that
      underlie the disease process in glaucoma. This also strengthens the hope that
      glaucoma therapy beyond IOP lowering will become available. Implementing this
      concept with clinical trials remains, however, a challenge. 

PMID- 25587913
TI  - Asymmetric sternotomy and sternal wound complications: assessment using 3
      dimensional computed tomography reconstruction.
AB  - OBJECTIVE: Wound complications after midline sternotomy result in significant
      morbidity and mortality. Despite many known risk factors, the influence of
      sternal asymmetry has largely been ignored. The purpose of this study was to
      assess the utility of 3-dimensional computed tomographic scan reconstructions to
      assess sternal asymmetry and determine its relationship with sternal wound
      infection. METHODS: A retrospective chart review was conducted for patients who
      underwent midline sternotomy and received a postoperative computed tomographic
      scan between 2009 and 2010. Cases were composed of all patients who had a sternal
      wound infection after undergoing sternotomy. Controls were randomly selected from
      patients without poststernotomy wound complications. Sternal asymmetry was
      defined as the difference between the left and the right sternal halves and was
      expressed as a percentage of the total sternal volume. RESULTS: Twenty-six cases
      were identified and 32 controls were selected as described earlier. The patients
      were similar in baseline characteristics and risk factors including age, sex,
      smoking status, diabetes, chronic obstructive pulmonary disease, preoperative
      creatinine, and operative time. Univariate factors associated with sternal wound
      infection include an asymmetry of 10% or greater, body mass index, and internal
      mammary artery harvest. In a multivariate logistic regression, independent
      predictors of sternal wound infection included an asymmetry of 10% or greater
      (odds ratio, 3.6; P = 0.03) and diabetes (odds ratio, 3.3; P = 0.0442).
      CONCLUSIONS: Our data suggest an association between asymmetric sternotomy and
      sternal wound infections. We recommend an assessment of sternal asymmetry to be
      performed in patients with sternal wound infection and if it is found to be 10%
      or greater, the surgeon should implement measures that stabilize the sternum.

PMID- 25587914
TI  - Preoperative vascular imaging for predicting intraoperative modification of
      peripheral arterial cannulation during minimally invasive mitral valve surgery.
AB  - OBJECTIVE: Minimally invasive mitral valve surgery using peripheral cannulation
      for cardiopulmonary bypass (CBP) is increasingly prevalent. Although conceptually
      straightforward, peripheral CBP involves challenges and risks specific to this
      method of perfusion. The utility of preoperative vascular imaging in predicting
      these technical challenges and preventing vascular complications was studied.
      METHODS: We performed a retrospective analysis of 73 consecutive patients
      undergoing minimally invasive mitral valve surgery using femorofemoral CBP with
      intraluminal aortic occlusion balloon catheter. All patients underwent
      preoperative computed tomography angiogram or magnetic resonance angiography to
      study the iliofemoral axes. RESULTS: None of the patients operated with this
      technique was found to have arterial stenoses. Patients with a femoral artery
      diameter of less than 7.3 mm needed bilateral or side-graft arterial cannulation
      significantly more frequently than patients with larger femoral arteries (46.2%
      vs 9.1%, P = 0.001). There was a trend toward more frequent modification of
      arterial cannulation strategy in patients with body surface area less than 1.7 m
      compared with larger patients (body surface area, 1.7-2.0) (26.3% vs 8.3%, P =
      0.07). Patients needing high CBP flow rate (>5 L/min) were no more likely to need
      dual arterial cannulation (18.2% vs 19.1%, P = 0.68). No patient experienced a
      vascular complication. CONCLUSIONS: This preliminary study suggests that
      preoperative vascular imaging and patient evaluation may predict difficulties
      with femoral cannulation and perfusion, which can lead to better preoperative
      planning and potentially prevent vascular complications. Further data will be
      accumulated and analyzed to confirm these findings.

PMID- 25587915
TI  - Concomitant grafting of both postbifurcation internal thoracic artery branches.
AB  - OBJECTIVE: We aimed to assess the clinical outcome and graft patency after
      concomitant grafting of both postbifurcation internal thoracic artery (ITA)
      branches. METHODS: Between 2007 and 2013, 17 patients (14 men; mean [SD] age, 60
      [9.3] years) underwent skeletonized bifurcated ITA grafting. Respective targets
      were restricted to non-left anterior descending (LAD) area. In all patients, a
      complementary standard ITA was used to graft the LAD artery. Graft patency was
      assessed by standard coronary angiography or serial multidetector computed
      tomography. RESULTS: Of the bifurcated conduits, 94% were right ITA. Respective
      right ITA target sets were first and second obtuse marginal arteries (M1-M2) (n =
      12), ramus-M1 (n = 2), and distal right coronary artery-posterior descending
      artery (n = 2). Right ITAs were mobilized retroaortic (via the transverse sinus)
      in 14 patients (82%) (to circumflex artery targets). Circumflex artery targets
      comprised 88.2% of all anastomoses (30/34). There were no early mortalities,
      myocardial infarctions, or hypoperfusion syndromes. During median follow-up of 44
      months (range, 3-63), there was no late mortality. Overall reintervention rate
      was 11.7%, and bifurcated ITA-related reintervention rate was 5.8%. At 5 years,
      freedom from major adverse cardiac or cerebrovascular event related to bifurcated
      ITA respective territory was 87% (Kaplan-Meier). Coronary imaging was achieved in
      76% of the patients (elective multidetector computed tomography, n = 9; symptoms
      directed coronary catheterization, n = 4). Bifurcation branch patency rate was
      88.4% (23/26) at a median of 3.5 years. CONCLUSIONS: Grafting both
      postbifurcation ITA branches is technically feasible and may be selectively
      considered. Current observations are valid for skeletonized conduits and limited
      to non-LAD targets. These preliminary findings should be corroborated by larger
      data sets.

PMID- 25587916
TI  - Processing of Materials for Regenerative Medicine Using Supercritical Fluid
      Technology.
AB  - The increase in the world demand of bone and cartilage replacement therapies
      urges the development of advanced synthetic scaffolds for regenerative purposes,
      not only providing mechanical support for tissue formation, but also promoting
      and guiding the tissue growth. Conventional manufacturing techniques have severe
      restrictions for designing these upgraded scaffolds, namely, regarding the use of
      organic solvents, shearing forces, and high operating temperatures. In this
      context, the use of supercritical fluid technology has emerged as an attractive
      solution to design solvent-free scaffolds and ingredients for scaffolds under
      mild processing conditions. The state-of-the-art on the technological endeavors
      for scaffold production using supercritical fluids is presented in this work with
      a critical review on the key processing parameters as well as the main advantages
      and limitations of each technique. A special stress is focused on the strategies
      suitable for the incorporation of bioactive agents (drugs, bioactive glasses, and
      growth factors) and the in vitro and in vivo performance of supercritical CO2
      processed scaffolds. 

PMID- 25587917
TI  - Current practice of periprocedural haematological management for patients
      undergoing image-guided procedures.
AB  - OBJECTIVE: To evaluate current UK practice of periprocedural haematological
      management for image-guided procedures in relation to Cardiovascular and
      Interventional Radiological Society guidelines, which provide recommendations
      according to bleeding risk of procedures from Category 1 (lowest) to 3 (highest).
      METHODS: Survey of practice in UK radiology departments conducted over a 1-year
      period RESULTS: 48 radiology departments responded. The percentage of departments
      that stop antithrombotics pre-procedurally are as follows (for Category 1, 2 and
      3, respectively): aspirin (31.3%, 43.8%, 54.2%); clopidogrel (54.2%, 68.8%,
      72.9%); therapeutic low-molecular-weight heparin (56.3%, 77.1%, 75.0%). The
      percentage of departments that perform pre-procedural laboratory testing are as
      follows (for Category 1, 2 and 3, respectively): international normalized ratio
      (INR; 81.3%, 95.8%, 93.8%); activated partial thrombin time ratio (APTTR; 60.4%,
      75.0%, 93.8%); platelet (77.1%, 91.7%, 95.7%); haemoglobin (70.8%, 85.4%, 87.5%).
      Mean threshold (standard deviation) of laboratory results for conducting
      procedures (Level 1, 2 and 3, respectively) are as follows: INR [1.53 (0.197),
      1.47 (0.186), 1.47 (0.188)]; APTTR [1.50 (0.392), 1.50 (0.339), 1.48 (0.344)];
      platelet count (x10(3) cells per microlitre) [74.4 (28.7), 79.9 (29.1), 80.5
      (29.3)]; haemoglobin (grams per decilitre) [9.05 (1.40), 9.00 (1.33), 8.92
      (1.21)]. No department practices conformed to current recommendations for (1) pre
      procedural cessation of antithrombotics and (2) pre-procedural laboratory
      testing. Two (4.2%) department practices conformed to recommendations for
      thresholds of haematological parameters. CONCLUSION: Current peri-procedural
      haematological management is variable and often does not conform to existing
      recommendations. Further research into the impact of this variation in practice
      on patient outcome is required. ADVANCES IN KNOWLEDGE: This study demonstrates
      wide variation in practice in haematological management for image-guided
      procedures.

PMID- 25587919
TI  - Gate-tunable photoresponse of defective graphene: from ultraviolet to visible.
AB  - We report the gate-tunable photoresponse of a defective graphene over the
      ultraviolet (UV) and the visible light illumination, where the defect was
      generated by plasma irradiation. Plasma induced Dirac point shift indicates the p
      doping effect. Interestingly the defective-graphene field effect transistor
      (defective-GFET) showed a negative shift upon UV illumination, whereas the device
      showed a positive shift under visible light illumination, along with the change
      in the photocurrent. The defective-GFET device showed a high photoresponsivity of
      37 mA W(-1) under visible light, that is ~3 times higher than that of the
      pristine graphene device. Photoinduced molecular desorption causes the UV light
      responsivity to 18 mA W(-1). This study shows that the tunable photodetector with
      high responsivity is feasible by introducing an artificial defect on graphene
      surface. 

PMID- 25587918
TI  - Head lice.
AB  - INTRODUCTION: Head louse infection is diagnosed by finding live lice, as eggs
      take 7 days to hatch (but a few may take longer, up to 13 days) and may appear
      viable for weeks after death of the egg. Infestation may be more likely in school
      children, with risks increased in children with more siblings or of lower
      socioeconomic group. Factors such as longer hair make diagnosis and treatment
      more difficult. METHODS AND OUTCOMES: We conducted a systematic review and aimed
      to answer the following clinical question: What are the effects of physically
      acting treatments for head lice? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to March 2014 (Clinical Evidence
      reviews are updated periodically; please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found six
      studies that met our inclusion criteria. We performed a GRADE evaluation of the
      quality of evidence for interventions. CONCLUSIONS: In this systematic review, we
      present information relating to the effectiveness and safety of the following
      interventions: 1,2-octanediol, dimeticone, herbal and essential oils, and
      isopropyl myristate.

PMID- 25587924
TI  - Structural insight into MtmC, a bifunctional ketoreductase-methyltransferase
      involved in the assembly of the mithramycin trisaccharide chain.
AB  - More and more post-PKS tailoring enzymes are recognized as being multifunctional
      and codependent on other tailoring enzymes. One of the recently discovered
      intriguing examples is MtmC, a bifunctional TDP-4-keto-d-olivose ketoreductase
      methyltransferase, which-in codependence with glycosyltransferase MtmGIV-is a key
      contributor to the biosynthesis of the critical trisaccharide chain of the
      antitumor antibiotic mithramycin (MTM), produced by Streptomyces argillaceus. We
      report crystal structures of three binary complexes of MtmC with its methylation
      cosubstrate SAM, its coproduct SAH, and a nucleotide TDP as well as crystal
      structures of two ternary complexes, MtmC-SAH-TDP-4-keto-d-olivose and MtmC-SAM
      TDP, in the range of 2.2-2.7 A resolution. The structures reveal general and
      sugar-specific recognition and catalytic structural features of MtmC. Depending
      on the catalytic function that is conducted by MtmC, it must bind either NADPH or
      SAM in the same cofactor binding pocket. A tyrosine residue (Tyr79) appears as a
      lid covering the sugar moiety of the substrate during the methyl transfer
      reaction. This residue swings out of the active site by ~180 degrees  in the
      absence of the substrate. This unique conformational change likely serves to
      release the methylated product and, possibly, to open the active site for binding
      the bulkier cosubstrate NADPH prior to the reduction reaction.

PMID- 25587925
TI  - Luteolin attenuate the D-galactose-induced renal damage by attenuation of
      oxidative stress and inflammation.
AB  - Luteolin is reported to have antioxidant and anti-inflammatory properties. In
      this study, we investigated the protective effect of luteolin against the renal
      damage induced by D-galactose (D-gal). The levels of creatinine (Cr) and urea
      nitrogen (BUN) were evaluated in plasma, kidney sections were stained with
      haematoxylin-eosin, followed by assessment of the antioxidant and anti
      inflammatory activity. Furthermore, we also investigated the expression of the
      p38 mitogen-activated protein kinase (p38 MAPK) and its phosphorylated
      activation. The results of luteolin treatment showed that the renal damages were
      attenuated. Luteolin could significantly ameliorate D-gal-induced oxidative
      damage and suppress the inflammatory response. Moreover, the result also shows
      that luteolin could significantly inhibit the p38 MAPK phosphorylation in the
      kidneys from the model of D-gal-treated mice. Therefore, our research suggests
      that luteolin might be involved in the attenuated oxidative stress and
      inflammatory responses, hence the protective effects against D-gal-induced renal
      damage.

PMID- 25587926
TI  - Reported foodborne outbreaks due to fresh produce in the United States and
      European Union: trends and causes.
AB  - The consumption of fruit and vegetables continues to rise in the United States
      and European Union due to healthy lifestyle recommendations. Meanwhile, the rate
      of foodborne illness caused by the consumption of these products remains high in
      both regions, representing a significant public health and financial issue. This
      study addresses the occurrence of reported foodborne outbreaks associated with
      fresh fruits and vegetables consumption in the United States and European Union
      during the period 2004-2012, where data are available. Special attention is paid
      to those pathogens responsible for these outbreaks, the mechanisms of
      contamination, and the fresh produce vehicles involved. Norovirus is shown to be
      responsible for most of the produce-related outbreaks, followed by Salmonella.
      Norovirus is mainly linked with the consumption of salad in the United States and
      of berries in the European Union, as demonstrated by the Multiple Correspondence
      Analysis (MCA). Salmonella was the leading cause of multistate produce outbreaks
      in the United States and was the pathogen involved in the majority of sprouts
      associated outbreaks. As is reflected in the MCA, the pattern of fresh produce
      outbreaks differed in the United States and European Union by the type of
      microorganism and the food vehicle involved. 

PMID- 25587927
TI  - Antimicrobial potential of cauliflower, broccoli, and okara byproducts against
      foodborne bacteria.
AB  - The antimicrobial potential of cauliflower, broccoli, and okara byproducts was
      assessed against Gram-positive and Gram-negative bacteria. Salmonella enterica
      serovar Typhimurium, Escherichia coli O157:H7, Bacillus cereus, and Listeria
      monocytogenes serovar 4b growth behavior was assessed under exposure to 5%
      vegetable byproducts added to the reference medium, buffered peptone water (0.1%
      [wt/vol]), at 37 degrees C. Although the byproducts were not effective against L.
      monocytogenes, they were bactericidal against Salmonella Typhimurium, E. coli
      O157:H7, and B. cereus. The most promising results were achieved with the
      cauliflower-Salmonella Typhimurium combination, because the bacterial population
      was reduced by 3.11 log10 cycles after 10 h of incubation at 37 degrees C as a
      result of 5% cauliflower addition. Further studies were carried out for this
      combination, at different cauliflower concentrations (0, 0.5, 1, 5, 10, and 15%)
      and at temperatures in the range of 5-37 degrees C. The greatest inactivation
      level (6.11 log10 cycles) was achieved at refrigeration temperature (5 degrees C)
      using 15% cauliflower addition. Both temperature and cauliflower concentration
      significantly (p<=0.05) influenced the Salmonella Typhimurium inactivation level.
      The kinetic parameters were adjusted to mathematical models. The modified
      Gompertz mathematical model provided an accurate fit (root-mean-square error
      (RMSE) [0.00009-0.21] and adjusted-R(2) [0.81-0.99]) to experimental Salmonella
      Typhimurium survival curves describing inactivation kinetics of the pathogen to
      the antimicrobial effect of cauliflower byproduct.

PMID- 25587928
TI  - Chemometric Analysis of Some Biologically Active Groups of Drugs on the Basis
      Chromatographic and Molecular Modeling Data.
AB  - In this work, three different groups of drugs such as 12 analgesic drugs, 11
      cardiovascular system drugs and 36 "other" compounds, respectively, were analyzed
      with cluster analysis (CA), principal component analysis (PCA) and factor
      analysis (FA) methods. All chemometric analysis were based on the chromatographic
      parameters (logk and logk(w)) determined by means of high-performance liquid
      chromatography (HPLC) and also by molecular modeling descriptors calculated using
      various computer programs (HyperChem, Dragon, and the VCCLAB). The clustering of
      compounds were obtained by CA (using various algorithm as e.g. Ward method or
      unweighted pair-group method using arithmetic averages as well as Euclidean or
      Manhattan distance), and allowed to build dendrograms linked drugs with similar
      physicochemical and pharmacological properties were discussed. Moreover, the
      analysis performed for analyzed groups of compounds with the use of FA or PCA
      methods indicated that almost all information reached in input chromatographic
      parameters as well as in molecular modeling descriptors can be explained by first
      two factors. Additionally, all analyzed drugs were clustered according to their
      chemical structure and pharmacological activity. Summarized, the performed
      classification analysis of studied drugs was focused on similarities and
      differences in methods being used for chemometric analysis as well as focused
      abilities to drugs classification (clustering) according to their molecular
      structures and pharmacological activity performed on the basis of chromatographic
      experimental and molecular modeling data. Thus, the most important application of
      statistically important molecular descriptors taken from QSRR models to
      classification analysis allow detailed biological (pharmacological)
      classification of analyzed drugs.

PMID- 25587929
TI  - Detection of Staphylococcus aureus by functional gold nanoparticle-based affinity
      surface-assisted laser desorption/ionization mass spectrometry.
AB  - Staphylococcus aureus is one of the common pathogenic bacteria responsible for
      bacterial infectious diseases and food poisoning. This study presents an
      analytical method based on the affinity nanoprobe-based mass spectrometry that
      enables detection of S. aureus in aqueous samples. A peptide aptamer
      DVFLGDVFLGDEC (DD) that can recognize S. aureus and methicillin-resistant S.
      aureus (MRSA) was used as the reducing agent and protective group to generate DD
      immobilized gold nanoparticles (AuNPs@DD) from one-pot reactions. The thiol group
      from cysteine in the peptide aptamer, i.e., DD, can interact with gold ions to
      generate DD-immobilized AuNPs in an alkaline solution. The generated AuNPs@DD has
      an absorption maximum at ~518 nm. The average particle size is 7.6 +/- 1.2 nm.
      Furthermore, the generated AuNPs@DD can selectively bind with S. aureus and MRSA.
      The conjugates of the target bacteria with AuNPs were directly analyzed by
      surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). The
      gold ions generated from the AuNPs@DD anchored on the target bacteria were
      monitored. Gold ions (m/z 197 and 394) were only generated from the conjugates of
      the target bacterium-AuNP@DD in the SALDI process. Thus, the gold ions could be
      used as the indicators for the presence of the target bacteria. The detection
      limit of S. aureus using this method is in the order of a few tens of cells. The
      low detection limit is due to the ease of generation of gold cluster ion derived
      from AuNPs under irradiation with a 355 nm laser beam. Apple juice mixed with S.
      aureus was used as the sample to demonstrate the suitability of the method for
      real-world application. Because of its low detection limit, this approach can
      potentially be used to screen the presence of S. aureus in complex samples. 

PMID- 25587930
TI  - Controlled formation of core-shell structures with uniform AlPO4 nanoshells.
AB  - Uniform AlPO4 nanoshells are successfully achieved on different core materials by
      controlling their formation kinetics in solution. The application of this coating
      protocol to LiCoO2 shows an obvious improvement in its battery performance. 

PMID- 25587931
TI  - Understanding viral neuraminidase inhibition by substituted difluorosialic acids.
AB  - Mechanism-based inhibition of influenza neuraminidases by difluorosialic acids
      (DFSA) is not only rendered highly specific by incorporation of 4-amino or 4
      guanidine substituents but also the half-life for reactivation is greatly
      increased. Measurement of rate constants for spontaneous hydrolysis of a series
      of such substituted DFSAs reveals, surprisingly, that inherent inductive effects
      play very little role in this rate reduction and that interactions with the
      enzyme are more important. 

PMID- 25587933
TI  - Correction to: Comparing the Personality Disorder Interview for DSM-IV (PDI-IV)
      and SCID-II Borderline Personality Disorder Scales: An Item-Response Theory
      Analysis.

PMID- 25587932
TI  - Pulse-coupled BZ oscillators with unequal coupling strengths.
AB  - Coupled chemical oscillators are usually studied with symmetric coupling, either
      between identical oscillators or between oscillators whose frequencies differ.
      Asymmetric connectivity is important in neuroscience, where synaptic strength
      inequality in neural networks commonly occurs. While the properties of the
      individual oscillators in some coupled chemical systems may be readily changed,
      enforcing inequality between the connection strengths in a reciprocal coupling is
      more challenging. We recently demonstrated a novel way of coupling chemical
      oscillators, which allows for manipulation of individual connection strengths.
      Here we study two identical, pulse-coupled Belousov-Zhabotinsky (BZ) oscillators
      with unequal connection strengths. When the pulse perturbations contain KBr
      (inhibitor), this system exhibits simple out-of-phase and complex oscillations,
      oscillatory-suppressed states as well as temporally periodic patterns (N : M) in
      which the two oscillators exhibit different numbers of peaks per cycle. The N : M
      patterns emerge due to the long-term effect of the inhibitory pulse
      perturbations, a feature that has not been considered in earlier works. Time
      delay was previously shown to have a profound effect on the system's behaviour
      when pulse coupling was inhibitory and the coupling strengths were equal. When
      the coupling is asymmetric, however, delay produces no qualitative change in
      behaviour, though the 1 : 2 temporal pattern becomes more robust. Asymmetry in
      instantaneous excitatory coupling via AgNO3 injection produces a previously
      unseen temporal pattern (1 : N patterns starting with a double peak) with time
      delay and high [AgNO3]. Numerical simulations of the behaviour agree well with
      theoretical predictions in asymmetrical pulse-coupled systems. 

PMID- 25587934
TI  - Sesquiterpenoid tropolone glycosides from Liriosma ovata.
AB  - Two new sesquiterpenoid tropolone glycosides, liriosmasides A (1) and B (2),
      along with two known compounds, secoxyloganin and oplopanpheside C, were isolated
      from a methanol extract of the roots of Liriosma ovata. The structures of 1 and 2
      were elucidated by spectroscopic methods including 1D and 2D NMR and by high
      resolution mass spectrometry involving an ultra-high-performance liquid
      chromatography-quadrupole-orbital ion trap mass spectrometric (UHPLC-Q-Orbitrap
      MS) method. Compound 1 showed weak inhibitory activity against HIV RNase H. 

PMID- 25587936
TI  - Nanocarrier-mediated inhibition of macrophage migration inhibitory factor
      attenuates secondary injury after spinal cord injury.
AB  - Spinal cord injury (SCI) can lead to permanent motor and sensory deficits.
      Following the initial traumatic insult, secondary injury mechanisms characterized
      by persistent heightened inflammation are initiated and lead to continued and
      pervasive cell death and tissue damage. Anti-inflammatory drugs such as
      methylprednisolone (MP) used clinically have ambiguous benefits with debilitating
      side effects. Typically, these drugs are administered systemically at high doses,
      resulting in toxicity and paradoxically increased inflammation. Furthermore,
      these drugs have a small time window postinjury (few hours) during which they
      need to be infused to be effective. As an alternative to MP, we investigated the
      effect of a small molecule inhibitor (Chicago sky blue, CSB) of macrophage
      migration inhibitory factor (MIF) for treating SCI. The pleiotropic cytokine MIF
      is known to contribute to upregulation of several pro-inflammatory cytokines in
      various disease and injury states. In vitro, CSB administration alleviated
      endotoxin-mediated inflammation in primary microglia and macrophages.
      Nanocarriers such as liposomes can potentially alleviate systemic side effects of
      high-dose therapy by enabling site-specific drug delivery to the spinal cord.
      However, the therapeutic window of 100 nm scale nanoparticle localization to the
      spinal cord after contusion injury is not fully known. Thus, we first
      investigated the ability of nanocarriers of different sizes to localize to the
      injured spinal cord up to 2 weeks postinjury. Results from the study showed that
      nanocarriers as large as 200 nm in diameter could extravasate into the injured
      spinal cord up to 96 h postinjury. We then formulated nanocarriers (liposomes)
      encapsulating CSB and administered them intravenously 48 h postinjury, within the
      previously determined 96 h therapeutic window. In vivo, in this clinically
      relevant contusion injury model in rats, CSB administration led to preservation
      of vascular and white matter integrity, improved wound healing, and an increase
      in levels of arginase and other transcripts indicative of a resolution phase of
      wound healing. This study demonstrates the potential of MIF inhibition in SCI and
      the utility of nanocarrier-mediated drug delivery selectively to the injured
      cord. 

PMID- 25587938
TI  - Differential effects of cerium oxide nanoparticles on rice, wheat, and barley
      roots: a fourier transform infrared (FT-IR) microspectroscopy study.
AB  - Cerium oxide nanoparticles (nCeO2) have extensive industrial applications, and
      concerns regarding their threat to the environment have been raised. This study
      includes structural analysis of intact root xylem of rice (Oryza sativaL.), wheat
      (Triticum aestivumL.), and barley (Hordeum vulgareL.) seedlings exposed to nCeO2
      suspensions (0, 62.5, 125, 250, and 500 mg L(-1)). Fourier transform infrared
      microspectroscopy was applied to determine compositional alterations in the root
      xylem, and principal component analysis (PCA) was carried out to examine spectral
      differences between nCeO2 treatments. Results demonstrated that nCeO2 at >= 125
      mg L(-1) changed the region of spectra around 1696-1760 cm(-1) in rice root, 125
      and 250 mg L(-1) modified 1744-1792 cm(-1) in wheat, and 62.5 and 125 mg L(-1)
      altered 1727-1760 cm(-1) in barley. PCA afforded the clustering of nCeO2
      treatments at 0 and 62.5 mg L(-1) in rice and wheat and 0 and 500 mg L(-1) in
      barley. Furthermore, major peaks at 1744 or 1760 cm(-1) appeared in primary PC
      and 1728 cm(-1) in secondary PC score loadings. These findings illustrated that
      nCeO2 induced compositional modifications in the root xylem of cereals. 

PMID- 25587935
TI  - Oral absorption enhancement of probucol by PEGylated G5 PAMAM dendrimer modified
      nanoliposomes.
AB  - Probucol (PB), an antioxidant drug, is commonly used as a lipid concentration
      lowering drug to reduce blood plasma cholesterol levels in the clinic. However,
      the therapeutic effects of this drug are negatively impacted by its poor water
      solubility and low oral absorption efficiency. In this study, a PEGylated G5
      PAMAM dendrimer (G5-PEG) modified nanoliposome was employed to increase water
      solubility, transepithelial transport, and oral absorption of PB. The uptake
      mechanism was explored in vitro in Caco-2 cells with the results suggesting that
      the absorption improvement of G5-PEG modified PB-liposome (PB-liposome/G5-PEG)
      was related to P-glycoprotein (P-gp) efflux pump but was independent of caveolae
      endocytosis pathways. Additionally, plasma lipid concentration lowering effects
      of PB-liposome/G5-PEG were evaluated in vivo in a LDLR-/- hyperlipidemia mouse
      model. Compared with saline treated group, treatment with PB-liposome/G5-PEG
      significantly inhibited the increase of plasma total cholesterol (TC) and
      triglyceride (TG) of mice induced by a high fat diet. Moreover, its lipid
      concentration lowering effects and plasma drug concentration were greater than PB
      alone or commercial PB tablets. Our results demonstrated that PB-liposome/G5-PEG
      significantly increased the oral absorption of PB and therefore significantly
      improved its pharmacodynamic effects. 

PMID- 25587939
TI  - Cumulative trauma, hyperarousal, and suicidality in the general population: a
      path analysis.
AB  - Although trauma exposure and posttraumatic stress disorder (PTSD) both have been
      linked to suicidal thoughts and behavior, the underlying basis for this
      relationship is not clear. In a sample of 357 trauma-exposed individuals from the
      general population, younger participant age, cumulative trauma exposure, and all
      three Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, PTSD
      clusters (reexperiencing, avoidance, and hyperarousal) were correlated with
      clinical levels of suicidality. However, logistic regression analysis indicated
      that when all PTSD clusters were considered simultaneously, only hyperarousal
      continued to be predictive. A path analysis confirmed that posttraumatic
      hyperarousal (but not other components of PTSD) fully mediated the relationship
      between extent of trauma exposure and degree of suicidal thoughts and behaviors. 

PMID- 25587941
TI  - Relay iron/chiral Bronsted acid catalysis: enantioselective hydrogenation of
      benzoxazinones.
AB  - An asymmetric hydrogenation reaction of benzoxazinones has been accomplished via
      a relay iron/chiral Bronsted acid catalysis. This approach provides a variety of
      chiral dihydrobenzoxazinones in good to high yields (75-96%) and
      enantioselectivities (up to 98:2 er). It is noteworthy that challenging 3-alkyl
      substituted substrates underwent highly enantioselective reduction. A key to
      success is the utilization of a nonchiral phosphine ligand to reduce
      disadvantageous background reactions through tuning the catalytic activity of
      Fe3(CO)12. 

PMID- 25587940
TI  - Kinetic and thermodynamic characterization of a novel low-temperature-active
      xylanase from Arthrobacter sp. GN16 isolated from the feces of Grus nigricollis.
AB  - We previously presented the cloning, heterologous expression, and
      characterization of a novel multidomain endoxylanase from Arthrobacter sp. GN16
      isolated from the feces of Grus nigricollis. Molecular and biochemical
      characterization studies indicate that the glycoside hydrolase (GH) family 10
      domain at the N-terminus of the multidomain xylanase (rXynAGN16L) is a low
      temperature-active endoxylanase. Many low-temperature-active enzymes contain
      regions of high local flexibility related to their kinetic and thermodynamic
      properties compared with mesophilic and thermophilic enzymes. However, the
      thermodynamic property of low-temperature-active xylanases, including rXynAGN16L,
      has rarely been reported. In this study, the kinetic and thermodynamic properties
      of rXynAGN16L were determined using different substrates and temperature
      conditions to completely characterize its activity properties. The kinetic
      property of rXynAGN16L is similar to some low-temperature-active GH 10
      endoxylanases. Moreover, the thermodynamic property indicates that rXynAGN16L is
      typically characterized as a low-temperature-active enzyme. 

PMID- 25587942
TI  - NMR signal enhancement for hyperpolarized fluids continuously generated in
      hydrogenation reactions with parahydrogen.
AB  - In the present study we analyze the factors which can lower hyperpolarization of
      fluids produced in a continuous flow regime by the parahydrogen-induced
      polarization technique. We use the findings of this analysis to examine the flow
      rate dependence of propane hyperpolarization produced in the heterogeneous
      propylene hydrogenation by parahydrogen over Rh/TiO2 catalyst. We have estimated
      the maximum attainable propane (1)H hyperpolarization yield and the corrected
      percentage of pairwise hydrogen addition in heterogeneous hydrogenation, which
      was found to be ~7%. The approach developed for polarization analysis is useful
      for the optimization of experimental setup and reaction conditions to obtain
      maximum hyperpolarization for parahydrogen-based catalyst-free continuously
      generated fluids applicable in biomedical magnetic resonance imaging. 

PMID- 25587944
TI  - Sharing individual patient data from clinical trials.

PMID- 25587945
TI  - Addressing the challenge of gray-zone medicine.

PMID- 25587946
TI  - Guiding choice--ethically influencing referrals in ACOs.

PMID- 25587947
TI  - On the death of a colleague.

PMID- 25587943
TI  - Epigenetic regulation in human melanoma: past and future.
AB  - The development and progression of melanoma have been attributed to independent
      or combined genetic and epigenetic events. There has been remarkable progress in
      understanding melanoma pathogenesis in terms of genetic alterations. However,
      recent studies have revealed a complex involvement of epigenetic mechanisms in
      the regulation of gene expression, including methylation, chromatin modification
      and remodeling, and the diverse activities of non-coding RNAs. The roles of gene
      methylation and miRNAs have been relatively well studied in melanoma, but other
      studies have shown that changes in chromatin status and in the differential
      expression of long non-coding RNAs can lead to altered regulation of key genes.
      Taken together, they affect the functioning of signaling pathways that influence
      each other, intersect, and form networks in which local perturbations disturb the
      activity of the whole system. Here, we focus on how epigenetic events intertwine
      with these pathways and contribute to the molecular pathogenesis of melanoma. 

PMID- 25587948
TI  - Trends in opioid analgesic abuse and mortality in the United States.
AB  - BACKGROUND: The use of prescription opioid medications has increased greatly in
      the United States during the past two decades; in 2010, there were 16,651 opioid
      related deaths. In response, hundreds of federal, state, and local interventions
      have been implemented. We describe trends in the diversion and abuse of
      prescription opioid analgesics using data through 2013. METHODS: We used five
      programs from the Researched Abuse, Diversion, and Addiction-Related Surveillance
      (RADARS) System to describe trends between 2002 and 2013 in the diversion and
      abuse of all products and formulations of six prescription opioid analgesics:
      oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol. The
      programs gather data from drug-diversion investigators, poison centers, substance
      abuse treatment centers, and college students. RESULTS: Prescriptions for opioid
      analgesics increased substantially from 2002 through 2010 in the United States
      but then decreased slightly from 2011 through 2013. In general, RADARS System
      programs reported large increases in the rates of opioid diversion and abuse from
      2002 to 2010, but then the rates flattened or decreased from 2011 through 2013.
      The rate of opioid-related deaths rose and fell in a similar pattern. Reported
      nonmedical use did not change significantly among college students. CONCLUSIONS:
      Postmarketing surveillance indicates that the diversion and abuse of prescription
      opioid medications increased between 2002 and 2010 and plateaued or decreased
      between 2011 and 2013. These findings suggest that the United States may be
      making progress in controlling the abuse of opioid analgesics. (Funded by the
      Denver Health and Hospital Authority.).

PMID- 25587949
TI  - Multiple-system atrophy.

PMID- 25587950
TI  - Images in clinical medicine. Actinomycetoma.

PMID- 25587951
TI  - Case records of the Massachusetts General Hospital. Case 2-2015. A 25-year-old
      man with abdominal pain, syncope, and hypotension.

PMID- 25587952
TI  - Practical, legal, and ethical issues in expanded access to investigational drugs.

PMID- 25587953
TI  - One-unit versus two-unit cord-blood transplantation.

PMID- 25587954
TI  - One-unit versus two-unit cord-blood transplantation.

PMID- 25587955
TI  - One-unit versus two-unit cord-blood transplantation.

PMID- 25587956
TI  - Cardiovascular risk and events and country income stratum.

PMID- 25587957
TI  - Cardiovascular risk and events and country income stratum.

PMID- 25587958
TI  - Cardiovascular risk and events and country income stratum.

PMID- 25587959
TI  - Cardiovascular risk and events and country income stratum.

PMID- 25587960
TI  - FOLFOXIRI and bevacizumab for metastatic colorectal cancer.

PMID- 25587961
TI  - FOLFOXIRI and bevacizumab for metastatic colorectal cancer.

PMID- 25587962
TI  - FOLFOXIRI and bevacizumab for metastatic colorectal cancer.

PMID- 25587964
TI  - Community-acquired pneumonia.

PMID- 25587963
TI  - Community-acquired pneumonia.

PMID- 25587965
TI  - Community-acquired pneumonia.

PMID- 25587966
TI  - Community-acquired pneumonia.

PMID- 25587967
TI  - Community-acquired pneumonia.

PMID- 25587968
TI  - Coronary heart disease and genetic variants with low phospholipase A2 activity.

PMID- 25587971
TI  - Images in clinical medicine. Intracranial arteriovenous malformation.

PMID- 25587972
TI  - In Vitro Effects of Resin Infiltration on Enamel Erosion Inhibition.
AB  - Resin-based materials that show promising effects for preventing the progression
      of erosion have been studied. This in vitro study evaluated the effects of
      applying resin-based materials, including resin infiltration, on previously
      eroded enamel subjected to erosive challenges. The influence of enamel surface
      etching prior to application of the material was also studied. Bovine enamel
      blocks were immersed in hydrochloric acid (HCl), 0.01 M (pH 2.3), for 30 seconds
      in order to form a softened erosion lesion. The blocks were then randomly divided
      into nine groups (n=12) and treated as follows: C = control without treatment;
      Hel = pit & fissure resin sealant (Helioseal Clear); Adh = two-step self-etching
      adhesive system (AdheSe); Tet = two-step conventional adhesive system (Tetric N
      bond); and Inf = infiltrant (Icon). The Helno, Adhno, Tetno, and Infno groups
      received the same materials without (or with no) surface conditioning. The depth
      of the material's penetration into softened erosion lesions was qualitatively
      analyzed using reflection and fluorescence confocal microscopy. After application
      of the materials, the blocks were immersed in HCl for two minutes; this step was
      followed by immersion in artificial saliva for 120 minutes four times a day for
      five days (erosive cycling). Both the enamel alteration and material thickness
      were analyzed using profilometry, and the results were submitted to Kruskal
      Wallis and Dunn tests (p>0.05). Images from the confocal microscopy showed
      minimal penetration of Adh/Adhno and deep penetration of Inf/Infno into the
      erosive lesions. The groups Hel, Adh, Inf, Tetno, and Infno resulted in the
      formation of a layer of material over the enamel, which was effective in
      inhibiting the progression of erosion. In conclusion, the infiltrant, with or
      without etching, was able to penetrate and protect the enamel against dental
      erosion. The other resin-based materials, except for the two-step conventional
      adhesive, were able to penetrate and inhibit the progression of erosive lesions
      only when they were applied after enamel etching. 

PMID- 25587973
TI  - Shear bond strength of porcelain veneers rebonded to enamel.
AB  - In this laboratory research, shear bond strength (SBS) and mode of failure of
      veneers rebonded to enamel in shear compression were determined. Three groups (A,
      B, and C; n=10 each) of mounted molar teeth were finished flat using wet 600-grit
      silicon carbide paper, and 30 leucite-reinforced porcelain veneers (5.0 * 0.75
      mm) were air abraded on the internal surface with 50 MUm aluminum oxide, etched
      with 9.5% hydrofluoric acid, and silanated. The control group (A) veneer
      specimens were bonded to enamel after etching with 37% phosphoric acid using
      bonding resin and a dual cure resin composite cement. Groups B and C were
      prepared similarly to group A with the exception that a release agent was placed
      before the veneer was positioned on the prepared enamel surface and the resin
      cement was subsequently light activated. The debonded veneers from groups B and C
      were placed in a casting burnout oven and heated to 454 degrees C/850 degrees F
      for 10 minutes to completely carbonize the resin cement and stay below the glass
      transition temperature (Tg) of the leucite-reinforced porcelain. The recovered
      veneers were then prepared for bonding. The previously bonded enamel surfaces in
      group B were air abraded using 50 MUm aluminum oxide followed by 37% phosphoric
      acid etching, while group C enamel specimens were acid etched only. All specimens
      were thermocycled between 5 degrees C and 55 degrees C for 2000 cycles using a 30
      second dwell time and stored in 37 degrees C deionized water for 2 weeks. SBS was
      determined at a crosshead speed of 1.0 mm/min. SBS results in MPa for the groups
      were (A) = 20.6+/-5.1, (B) = 18.1+/-5.5, and (C) = 17.2+/-6.1. One-way analysis
      of variance indicated that there were no significant interactions (alpha=0.05),
      and Tukey-Kramer post hoc comparisons (alpha=0.05) detected no significant
      pairwise differences. An adhesive mode of failure at the enamel interface was
      observed to occur more often in the experimental groups (B = 40%, C = 50%).
      Rebonding the veneers produced SBS values that were not significantly different
      from the control group. Also, no significant difference in SBS values were
      observed whether the debonded enamel surface was air abraded and acid etched or
      acid etched only. 

PMID- 25587974
TI  - A high fuel consumption efficiency management scheme for PHEVs using an adaptive
      genetic algorithm.
AB  - A high fuel efficiency management scheme for plug-in hybrid electric vehicles
      (PHEVs) has been developed. In order to achieve fuel consumption reduction, an
      adaptive genetic algorithm scheme has been designed to adaptively manage the
      energy resource usage. The objective function of the genetic algorithm is
      implemented by designing a fuzzy logic controller which closely monitors and
      resembles the driving conditions and environment of PHEVs, thus trading off
      between petrol versus electricity for optimal driving efficiency. Comparison
      between calculated results and publicized data shows that the achieved efficiency
      of the fuzzified genetic algorithm is better by 10% than existing schemes. The
      developed scheme, if fully adopted, would help reduce over 600 tons of CO2
      emissions worldwide every day. 

PMID- 25587976
TI  - Thermocouple and infrared sensor-based measurement of temperature distribution in
      metal cutting.
AB  - In metal cutting, the magnitude of the temperature at the tool-chip interface is
      a function of the cutting parameters. This temperature directly affects
      production; therefore, increased research on the role of cutting temperatures can
      lead to improved machining operations. In this study, tool temperature was
      estimated by simultaneous temperature measurement employing both a K-type
      thermocouple and an infrared radiation (IR) pyrometer to measure the tool-chip
      interface temperature. Due to the complexity of the machining processes, the
      integration of different measuring techniques was necessary in order to obtain
      consistent temperature data. The thermal analysis results were compared via the
      ANSYS finite element method. Experiments were carried out in dry machining using
      workpiece material of AISI 4140 alloy steel that was heat treated by an induction
      process to a hardness of 50 HRC. A PVD TiAlN-TiN-coated WNVG 080404-IC907 carbide
      insert was used during the turning process. The results showed that with
      increasing cutting speed, feed rate and depth of cut, the tool temperature
      increased; the cutting speed was found to be the most effective parameter in
      assessing the temperature rise. The heat distribution of the cutting tool, tool
      chip interface and workpiece provided effective and useful data for the
      optimization of selected cutting parameters during orthogonal machining. 

PMID- 25587977
TI  - Received signal strength recovery in green WLAN indoor positioning system using
      singular value thresholding.
AB  - Green WLAN is a promising technique for accessing future indoor Internet
      services. It is designed not only for high-speed data communication purposes but
      also for energy efficiency. The basic strategy of green WLAN is that all the
      access points are not always powered on, but rather work on-demand. Though
      powering off idle access points does not affect data communication, a serious
      asymmetric matching problem will arise in a WLAN indoor positioning system due to
      the fact the received signal strength (RSS) readings from the available access
      points are different in their offline and online phases. This asymmetry problem
      will no doubt invalidate the fingerprint algorithm used to estimate the mobile
      device location. Therefore, in this paper we propose a green WLAN indoor
      positioning system, which can recover RSS readings and achieve good localization
      performance based on singular value thresholding (SVT) theory. By solving the
      nuclear norm minimization problem, SVT recovers not only the radio map, but also
      online RSS readings from a sparse matrix by sensing only a fraction of the RSS
      readings. We have implemented the method in our lab and evaluated its
      performances. The experimental results indicate the proposed system could recover
      the RSS readings and achieve good localization performance. 

PMID- 25587975
TI  - A customized metal oxide semiconductor-based gas sensor array for onion quality
      evaluation: system development and characterization.
AB  - A gas sensor array, consisting of seven Metal Oxide Semiconductor (MOS) sensors
      that are sensitive to a wide range of organic volatile compounds was developed to
      detect rotten onions during storage. These MOS sensors were enclosed in a
      specially designed Teflon chamber equipped with a gas delivery system to pump
      volatiles from the onion samples into the chamber. The electronic circuit mainly
      comprised a microcontroller, non-volatile memory chip, and trickle-charge real
      time clock chip, serial communication chip, and parallel LCD panel. User
      preferences are communicated with the on-board microcontroller through a
      graphical user interface developed using LabVIEW. The developed gas sensor array
      was characterized and the discrimination potential was tested by exposing it to
      three different concentrations of acetone (ketone), acetonitrile (nitrile), ethyl
      acetate (ester), and ethanol (alcohol). The gas sensor array could differentiate
      the four chemicals of same concentrations and different concentrations within the
      chemical with significant difference. Experiment results also showed that the
      system was able to discriminate two concentrations (196 and 1964 ppm) of
      methlypropyl sulfide and two concentrations (145 and 1452 ppm) of 2-nonanone, two
      key volatile compounds emitted by rotten onions. As a proof of concept, the gas
      sensor array was able to achieve 89% correct classification of sour skin infected
      onions. The customized low-cost gas sensor array could be a useful tool to detect
      onion postharvest diseases in storage. 

PMID- 25587978
TI  - A speedy cardiovascular diseases classifier using multiple criteria decision
      analysis.
AB  - Each year, some 30 percent of global deaths are caused by cardiovascular
      diseases. This figure is worsening due to both the increasing elderly population
      and severe shortages of medical personnel. The development of a cardiovascular
      diseases classifier (CDC) for auto-diagnosis will help address solve the problem.
      Former CDCs did not achieve quick evaluation of cardiovascular diseases. In this
      letter, a new CDC to achieve speedy detection is investigated. This investigation
      incorporates the analytic hierarchy process (AHP)-based multiple criteria
      decision analysis (MCDA) to develop feature vectors using a Support Vector
      Machine. The MCDA facilitates the efficient assignment of appropriate weightings
      to potential patients, thus scaling down the number of features. Since the new
      CDC will only adopt the most meaningful features for discrimination between
      healthy persons versus cardiovascular disease patients, a speedy detection of
      cardiovascular diseases has been successfully implemented. 

PMID- 25587979
TI  - Development and experimental validation of a numerical tool for structural health
      and usage monitoring systems based on chirped grating sensors.
AB  - The interest of the aerospace industries in structural health and usage
      monitoring systems is continuously increasing. Among the techniques available in
      literature those based on Fibre Bragg Grating sensors are much promising thanks
      to their peculiarities. Different Chirped Bragg Grating sensor configurations
      have been investigated in this paper. Starting from a numerical model capable of
      simulating the spectral response of a grating subjected to a generic strain
      profile (direct problem), a new code has been developed, allowing strain
      reconstruction from the experimental validation of the program, carried out
      through different loading cases applied on a chirped grating. The wavelength of
      the reflection spectrum for a chirped FBG has a one-to-one correspondence to the
      position along the gauge section, thus allowing strain reconstruction over the
      entire sensor length. Tests conducted on chirped FBGs also evidenced their
      potential for SHM applications, if coupled with appropriate numerical strain
      reconstructions tools. Finally, a new class of sensors-Draw Tower Grating arrays
      has been studied. These sensors are applicable to distributed sensing and load
      reconstruction over large structures, thanks to their greater length. Three
      configurations have been evaluated, having different spatial and spectral
      characteristics, in order to explore possible applications of such sensors to SHM
      systems. 

PMID- 25587980
TI  - Frequency noise suppression of a single mode laser with an unbalanced fiber
      interferometer for subnanometer interferometry.
AB  - We present a method of noise suppression of laser diodes by an unbalanced
      Michelson fiber interferometer. The unstabilized laser source is represented by
      compact planar waveguide external cavity laser module, ORIONTM (Redfern
      Integrated Optics, Inc.), working at 1540.57 nm with a 1.5-kHz linewidth. We
      built up the unbalanced Michelson interferometer with a 2.09 km-long arm based on
      the standard telecommunication single-mode fiber (SMF-28) spool to suppress the
      frequency noise by the servo-loop control by 20 dB to 40 dB within the Fourier
      frequency range, remaining the tuning range of the laser frequency. 

PMID- 25587981
TI  - Improving the performance of an electronic nose by wine aroma training to
      distinguish between drip coffee and canned coffee.
AB  - Coffee aroma, with more than 600 components, is considered as one of the most
      complex food aromas. Although electronic noses have been successfully used for
      objective analysis and differentiation of total coffee aromas, it is difficult to
      use them to describe the specific features of coffee aroma (i.e., the type of
      smell). This is because data obtained by electronic noses are generally based on
      electrical resistance/current and samples are distinguished by principal
      component analysis. In this paper, we present an electronic nose that is capable
      of learning the wine related aromas using the aroma kit "Le Nez du Vin," and the
      potential to describe coffee aroma in a similar manner comparable to how wine
      experts describe wine aroma. The results of our investigation showed that the
      aromas of three drip coffees were more similar to those of pine and honey in the
      aroma kit than to the aromas of three canned coffees. Conversely, the aromas of
      canned coffees were more similar to the kit coffee aroma. In addition, the
      aromatic patterns of coffees were different from those of green tea and red wine.
      Although further study is required to fit the data to human olfaction, the
      presented method and the use of vocabularies in aroma kits promise to enhance
      objective discrimination and description of aromas by electronic noses. 

PMID- 25587982
TI  - Cumulative effect and predictive value of genetic variants associated with type 2
      diabetes in Han Chinese: a case-control study.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified dozens of
      single nucleotide polymorphisms (SNPs) associated with type 2 diabetes risk. We
      have previously confirmed the associations of genetic variants in HHEX, CDKAL1,
      VEGFA and FTO with type 2 diabetes in Han Chinese. However, the cumulative effect
      and predictive value of these GWAS identified SNPs on the risk of type 2 diabetes
      in Han Chinese are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We conducted
      a two-stage case-control study consisting of 2,925 cases and 3,281 controls to
      examine the association of 30 SNPs identified by GWAS with type 2 diabetes in Han
      Chinese. Significant associations were found for proxy SNPs at KCNQ1 [odds ratio
      (OR) = 1.41, P = 9.91 * 10-16 for rs2237897], CDKN2A/CDKN2B (OR = 1.30, P = 1.34
      * 10-10 for rs10811661), CENTD2 (OR = 1.28, P = 9.88 * 10-4 for rs1552224) and
      SLC30A8 (OR = 1.19, P = 1.43 * 10-5 for rs13266634). We further evaluated the
      cumulative effect on type 2 diabetes of these 4 SNPs, in combination with 5 SNPs
      at HHEX, CDKAL1, VEGFA and FTO reported previously. Individuals carrying 12 or
      more risk alleles had a nearly 4-fold increased risk for developing type 2
      diabetes compared with those carrying less than 6 risk alleles [adjusted OR =
      3.68, 95% confidence interval (CI): 2.76-4.91]. Adding the genetic factors to
      clinical factors slightly improved the prediction of type 2 diabetes, with the
      area under the receiver operating characteristic curve increasing from 0.76 to
      0.78. However, the difference was statistically significant (P < 0.0001).
      CONCLUSIONS/SIGNIFICANCE: We confirmed associations of SNPs in KCNQ1,
      CDKN2A/CDKN2B, CENTD2 and SLC30A8 with type 2 diabetes in Han Chinese. The
      utilization of genetic information may improve the accuracy of risk prediction in
      combination with clinical characteristics for type 2 diabetes.

PMID- 25587985
TI  - Right tail of the distribution of depressive symptoms is stable and follows an
      exponential curve during middle adulthood.
AB  - BACKGROUND: Previous research has reported that the mean of depressive symptoms
      is stable in the general population through middle adulthood. To understand the
      stability of depressive symptoms during middle adulthood, we investigated the
      nature of the distribution of depressive symptoms. METHODS: We analyzed 24,890
      subjects aged 15 to 84 years who participated in the Active Survey of Health and
      Welfare, Japan. Depressive symptoms were assessed using the Japanese version of
      the Center for Epidemiologic Studies Depression Scale (CES-D). The descriptive
      statistics and frequency curves of the distributions were then compared according
      to age group. RESULTS: The distribution of depressive symptoms was stable through
      middle adulthood. The right tail which covers clinical depression was more stable
      than the left tail or peak of the distributions. The right tail of the
      distribution during middle adulthood exhibited a linear pattern with a log-normal
      scale. CONCLUSIONS: The right tail of the distribution of depressive symptoms is
      stable and exhibits an exponential pattern during middle adulthood.

PMID- 25587983
TI  - Detection and quantification of microparticles from different cellular lineages
      using flow cytometry. Evaluation of the impact of secreted phospholipase A2 on
      microparticle assessment.
AB  - Microparticles, also called microvesicles, are submicron extracellular vesicles
      produced by plasma membrane budding and shedding recognized as key actors in
      numerous physio(patho)logical processes. Since they can be released by virtually
      any cell lineages and are retrieved in biological fluids, microparticles appear
      as potent biomarkers. However, the small dimensions of microparticles and soluble
      factors present in body fluids can considerably impede their quantification.
      Here, flow cytometry with improved methodology for microparticle resolution was
      used to detect microparticles of human and mouse species generated from
      platelets, red blood cells, endothelial cells, apoptotic thymocytes and cells
      from the male reproductive tract. A family of soluble proteins, the secreted
      phospholipases A2 (sPLA2), comprises enzymes concomitantly expressed with
      microparticles in biological fluids and that catalyze the hydrolysis of membrane
      phospholipids. As sPLA2 can hydrolyze phosphatidylserine, a phospholipid
      frequently used to assess microparticles, and might even clear microparticles, we
      further considered the impact of relevant sPLA2 enzymes, sPLA2 group IIA, V and
      X, on microparticle quantification. We observed that if enriched in fluids,
      certain sPLA2 enzymes impair the quantification of microparticles depending on
      the species studied, the source of microparticles and the means of detection
      employed (surface phosphatidylserine or protein antigen detection). This study
      provides analytical considerations for appropriate interpretation of
      microparticle cytofluorometric measurements in biological samples containing
      sPLA2 enzymes. 

PMID- 25587984
TI  - Identification of microRNAs and target genes in the fruit and shoot tip of Lycium
      chinense: a traditional Chinese medicinal plant.
AB  - Although Lycium chinense (goji berry) is an important traditional Chinese
      medicinal plant, little genome information is available for this plant,
      particularly at the small-RNA level. Recent findings indicate that the
      evolutionary role of miRNAs is very important for a better understanding of gene
      regulation in different plant species. To elucidate small RNAs and their
      potential target genes in fruit and shoot tissues, high-throughput RNA sequencing
      technology was used followed by qRT-PCR and RLM 5'-RACE experiments. A total of
      60 conserved miRNAs belonging to 31 families and 30 putative novel miRNAs were
      identified. A total of 62 significantly differentially expressed miRNAs were
      identified, of which 15 (14 known and 1 novel) were shoot-specific, and 12 (7
      known and 5 novel) were fruit-specific. Additionally, 28 differentially expressed
      miRNAs were recorded as up-regulated in fruit tissues. The predicted potential
      targets were involved in a wide range of metabolic and regulatory pathways. GO
      (Gene Ontology) enrichment analysis and the KEGG (Kyoto Encyclopedia of Genes and
      Genomes) database revealed that "metabolic pathways" is the most significant
      pathway with respect to the rich factor and gene numbers. Moreover, five miRNAs
      were related to fruit maturation, lycopene biosynthesis and signaling pathways,
      which might be important for the further study of fruit molecular biology. This
      study is the first, to detect known and novel miRNAs, and their potential
      targets, of L. chinense. The data and findings that are presented here might be a
      good source for the functional genomic study of medicinal plants and for
      understanding the links among diversified biological pathways. 

PMID- 25587986
TI  - Biomimetic remineralization of demineralized dentine using scaffold of CMC/ACP
      nanocomplexes in an in vitro tooth model of deep caries.
AB  - Currently, it is still a tough task for dentists to remineralize dentine in deep
      caries. The aim of this study was to remineralize demineralized dentine in a
      tooth model of deep caries using nanocomplexes of carboxymethyl
      chitosan/amorphous calcium phosphate (CMC/ACP) based on mimicking the stabilizing
      effect of dentine matrix protein 1 (DMP1) on ACP in the biomineralization of
      dentine. The experimental results indicate that CMC can stabilize ACP to form
      nanocomplexes of CMC/ACP, which is able to be processed into scaffolds by
      lyophilization. In the single-layer collagen model, ACP nanoparticles are
      released from scaffolds of CMC/ACP nanocomplexes dissolved and then infiltrate
      into collagen fibrils via the gap zones (40 nm) to accomplish intrafibrillar
      mineralization of collagen. With this method, the completely demineralized
      dentine was partially remineralized in the tooth mode. This is a bottom-up
      remineralizing strategy based on non-classical crystallization theory. Since
      nanocomplexes of CMC/ACP show a promising effect of remineralization on
      demineralized dentine via biomimetic strategy, thereby preserving dentinal tissue
      to the maximum extent possible, it would be a potential indirect pulp capping
      (IPC) material for the management of deep caries during vital pulp therapy based
      on the concept of minimally invasive dentistry (MID). 

PMID- 25587989
TI  - Sitting on a sloping seat does not reduce the strain sustained by the postural
      chain.
AB  - The objective of this study was to explore the effect of a forward sloping seat
      on posture and muscular activity of the trunk and lower limbs. To this aim,
      twelve asymptomatic participants were tested in six conditions varying seat slope
      (0 degrees , 15 degrees  forward) and height (high, medium, low). Angular
      position of head, trunk and pelvis was assessed with an inertial orientation
      system, and muscular activity of 11 superficial postural muscles located in the
      trunk and lower limbs was estimated using normalized EMG. Results showed that a
      forward sloping seat, compared to a flat seat, induced a greater activity of the
      soleus (p<0.01), vastus lateralis (p<0.05) and vastus medialis (p<0.05), as well
      a lower hip flexion (p<0.01). In contrast, no significant variation of head,
      trunk and pelvis angular position was observed according to seat slope. It was
      concluded that forward sloping seats increase the load sustained by the lower
      limbs, without a systematic improvement of body posture. 

PMID- 25587987
TI  - Event-related potentials reveal preserved attention allocation but impaired
      emotion regulation in patients with epilepsy and comorbid negative affect.
AB  - Patients with epilepsy have a high prevalence of comorbid mood disorders. This
      study aims to evaluate whether negative affect in epilepsy is associated with
      dysfunction of emotion regulation. Event-related potentials (ERPs) are used in
      order to unravel the exact electrophysiological time course and investigate
      whether a possible dysfunction arises during early (attention) and/or late
      (regulation) stages of emotion control. Fifty epileptic patients with (n = 25)
      versus without (n = 25) comorbid negative affect plus twenty-five matched
      controls were recruited. ERPs were recorded while subjects performed a face- or
      house-matching task in which fearful, sad or neutral faces were presented either
      at attended or unattended spatial locations. Two ERP components were analyzed:
      the early vertex positive potential (VPP) which is normally enhanced for faces,
      and the late positive potential (LPP) that is typically larger for emotional
      stimuli. All participants had larger amplitude of the early face-sensitive VPP
      for attended faces compared to houses, regardless of their emotional content. By
      contrast, in patients with negative affect only, the amplitude of the LPP was
      significantly increased for unattended negative emotional expressions. These VPP
      results indicate that epilepsy with or without negative affect does not interfere
      with the early structural encoding and attention selection of faces. However, the
      LPP results suggest abnormal regulation processes during the processing of
      unattended emotional faces in patients with epilepsy and comorbid negative
      affect. In conclusion, this ERP study reveals that early object-based attention
      processes are not compromised by epilepsy, but instead, when combined with
      negative affect, this neurological disease is associated with dysfunction during
      the later stages of emotion regulation. As such, these new neurophysiological
      findings shed light on the complex interplay of epilepsy with negative affect
      during the processing of emotional visual stimuli and in turn might help to
      better understand the etiology and maintenance of mood disorders in epilepsy. 

PMID- 25587990
TI  - Amyopathic dermatomyositis-related thrombophilia.

PMID- 25587993
TI  - Revisiting susceptibility testing in MDR-TB by a standardized quantitative
      phenotypic assessment in a European multicentre study.
AB  - OBJECTIVES: Treatment outcome of MDR-TB is critically dependent on the proper use
      of second-line drugs as per the result of in vitro drug susceptibility testing
      (DST). We aimed to establish a standardized DST procedure based on quantitative
      determination of drug resistance and compared the results with those of genotypes
      associated with drug resistance. METHODS: The protocol, based on MGIT 960 and the
      TB eXiST software, was evaluated in nine European reference laboratories.
      Resistance detection at a screening drug concentration was followed by
      determination of resistance levels and estimation of the resistance proportion.
      Mutations in 14 gene regions were investigated using established techniques.
      RESULTS: A total of 139 Mycobacterium tuberculosis isolates from patients with
      MDR-TB and resistance beyond MDR-TB were tested for 13 antituberculous drugs:
      isoniazid, rifampicin, rifabutin, ethambutol, pyrazinamide, streptomycin, para
      aminosalicylic acid, ethionamide, amikacin, capreomycin, ofloxacin, moxifloxacin
      and linezolid. Concordance between phenotypic and genotypic resistance was >80%,
      except for ethambutol. Time to results was short (median 10 days). High-level
      resistance, which precludes the therapeutic use of an antituberculous drug, was
      observed in 49% of the isolates. The finding of a low or intermediate resistance
      level in 16% and 35% of the isolates, respectively, may help in designing an
      efficient personalized regimen for the treatment of MDR-TB patients. CONCLUSIONS:
      The automated DST procedure permits accurate and rapid quantitative resistance
      profiling of first- and second-line antituberculous drugs. Prospective validation
      is warranted to determine the impact on patient care.

PMID- 25587991
TI  - Life-style and genome structure of marine Pseudoalteromonas siphovirus B8b
      isolated from the northwestern Mediterranean Sea.
AB  - Marine viruses (phages) alter bacterial diversity and evolution with impacts on
      marine biogeochemical cycles, and yet few well-developed model systems limit
      opportunities for hypothesis testing. Here we isolate phage B8b from the
      Mediterranean Sea using Pseudoalteromonas sp. QC-44 as a host and characterize it
      using myriad techniques. Morphologically, phage B8b was classified as a member of
      the Siphoviridae family. One-step growth analyses showed that this siphovirus had
      a latent period of 70 min and released 172 new viral particles per cell. Host
      range analysis against 89 bacterial host strains revealed that phage B8b infected
      3 Pseudoalteromonas strains (52 tested, >99.9% 16S rRNA gene nucleotide identity)
      and 1 non-Pseudoaltermonas strain belonging to Alteromonas sp. (37 strains from 6
      genera tested), which helps bound the phylogenetic distance possible in a phage
      mediated horizontal gene transfer event. The Pseudoalteromonas phage B8b genome
      size was 42.7 kb, with clear structural and replication modules where the former
      were delineated leveraging identification of 16 structural genes by virion
      structural proteomics, only 4 of which had any similarity to known structural
      proteins. In nature, this phage was common in coastal marine environments in both
      photic and aphotic layers (found in 26.5% of available viral metagenomes), but
      not abundant in any sample (average per sample abundance was 0.65% of the reads).
      Together these data improve our understanding of siphoviruses in nature, and
      provide foundational information for a new 'rare virosphere' phage-host model
      system.

PMID- 25587992
TI  - Plasma IL-5 concentration and subclinical carotid atherosclerosis.
AB  - OBJECTIVE: Genetic variants robustly associated with coronary artery disease were
      reported in the vicinity of the interleukin (IL)-5 locus, and animal studies
      suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this
      work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis,
      as determined by measures of baseline severity and change over time of carotid
      intima-media thickness (cIMT). METHODS: We used biobank and databases of IMPROVE,
      a large European prospective cohort study of high-risk individuals (n = 3534)
      free of clinically overt cardiovascular disease at enrollment, in whom composite
      and segment-specific measures of cIMT were recorded at baseline and after 15 and
      30 months. IL-5 was measured with an immunoassay in plasma samples taken at
      baseline. RESULTS: IL-5 levels were lower in women than in men, lower in the
      South than in North of Europe, and showed positive correlations with most
      established risk factors. IL-5 showed significant inverse relationships with cIMT
      change over time in the common carotid segment in women, but no significant
      relationships to baseline cIMT in either men or women. CONCLUSIONS: Our results
      suggest that IL-5 may be part of protective mechanisms operating in early
      atherosclerosis, at least in women. However, the relationships are weak and
      whereas IL-5 has been proposed as a potential molecular target to treat
      allergies, it is difficult to envisage such a scenario in coronary artery
      disease.

PMID- 25587994
TI  - Comprehensive physicochemical, pharmacokinetic and activity profiling of anti-TB
      agents.
AB  - OBJECTIVES: The discovery and development of TB drugs has met limited success,
      with two new drugs approved over the last 40 years. Part of the difficulty
      resides in the lack of well-established in vitro or in vivo targets of potency
      and physicochemical and pharmacokinetic parameters. In an attempt to benchmark
      and compare such properties for anti-TB agents, we have experimentally determined
      and compiled these parameters for 36 anti-TB compounds, using standardized and
      centralized assays, thus ensuring direct comparability across drugs and drug
      classes. METHODS: Potency parameters included growth inhibition, cidal activity
      against growing and non-growing bacteria and activity against intracellular
      mycobacteria. Pharmacokinetic parameters included basic physicochemical
      properties, solubility, permeability and metabolic stability. We then attempted
      to establish correlations between physicochemical, in vitro and in vivo
      pharmacokinetic and pharmacodynamic indices to tentatively inform future drug
      discovery efforts. RESULTS: Two-thirds of the compounds tested showed
      bactericidal and intramacrophage activity. Most compounds exhibited favourable
      solubility, permeability and metabolic stability in standard in vitro
      pharmacokinetic assays. An analysis of human pharmacokinetic parameters revealed
      associations between lipophilicity and volume of distribution, clearance, plasma
      protein binding and oral bioavailability. Not surprisingly, most compounds with
      favourable pharmacokinetic properties complied with Lipinski's rule of five.
      CONCLUSIONS: However, most attempts to detect in vitro-in vivo correlations were
      unsuccessful, emphasizing the challenges of anti-TB drug discovery. The objective
      of this work is to provide a reference dataset for the TB drug discovery
      community with a focus on comparative in vitro potency and pharmacokinetics.

PMID- 25587995
TI  - The transcriptomic response of Acinetobacter baumannii to colistin and doripenem
      alone and in combination in an in vitro pharmacokinetics/pharmacodynamics model.
AB  - OBJECTIVES: Colistin remains a last-line treatment for MDR Acinetobacter
      baumannii and combined use of colistin and carbapenems has shown synergistic
      effects against MDR strains. In order to understand the bacterial responses to
      these antibiotics, we analysed the transcriptome of A. baumannii following
      exposure to each. METHODS: RNA sequencing was employed to determine changes in
      the transcriptome following treatment with colistin and doripenem, both alone and
      in combination, using an in vitro pharmacokinetics (PK)/pharmacodynamics model to
      mimic the PK of both antibiotics in patients. RESULTS: After treatment with
      colistin (continuous infusion at 2 mg/L), >400 differentially regulated genes
      were identified, including many associated with outer membrane biogenesis, fatty
      acid metabolism and phospholipid trafficking. No genes were differentially
      expressed following treatment with doripenem (Cmax 25 mg/L, t1/2 1.5 h) for 15
      min, but 45 genes were identified as differentially expressed after 1 h of growth
      under this condition. Treatment of A. baumannii with both colistin and doripenem
      together for 1 h resulted in >450 genes being identified as differentially
      expressed. More than 70% of these gene expression changes were also observed
      following colistin treatment alone. CONCLUSIONS: These data suggest that colistin
      causes gross damage to the outer membrane, facilitates lipid exchange between the
      inner and outer membrane and alters the normal asymmetric outer membrane
      composition. The transcriptional response to colistin was highly similar to that
      observed for an LPS-deficient strain, indicating that many of the observed
      changes are responses to outer membrane instability resulting from LPS loss.

PMID- 25587997
TI  - Analysis of thin-film polymers using attenuated total internal reflection-Raman
      microspectroscopy.
AB  - Two methods commonly employed for molecular surface analysis and thin-film
      analysis of microscopic areas are attenuated total reflection infrared (ATR-IR)
      microspectroscopy and confocal Raman microspectroscopy. In the former method, the
      depth of the evanescent probe beam can be controlled by the wavelength of light,
      the angle of incidence, or the refractive index of the internal reflection
      element. Because the penetration depth is proportional to the wavelength of
      light, one could interrogate a smaller film thickness by moving from the mid
      infrared region to the visible region employing Raman spectroscopy. The
      investigation of ATR Raman microspectroscopy, a largely unexplored technique
      available to Raman microspectroscopy, was carried out. A Renishaw inVia Raman
      microscope was externally modified and used in conjunction with a solid immersion
      lens (SIL) to perform ATR Raman experiments. Thin-film polymer samples were
      analyzed to explore the theoretical sampling depth for experiments conducted
      without the SIL, with the SIL, and with the SIL using evanescent excitation. The
      feasibility of micro-ATR Raman was examined by collecting ATR spectra from films
      whose thickness measured from 200 to 60 nm. Films of these thicknesses were
      present on a much thicker substrate, and features from the underlying substrate
      did not become visible until the thin film reached a thickness of 68 nm. 

PMID- 25587996
TI  - Avibactam confers susceptibility to a large proportion of ceftazidime-resistant
      Pseudomonas aeruginosa isolates recovered from cystic fibrosis patients.

PMID- 25587998
TI  - No evidence of complementary water use along a plant species richness gradient in
      temperate experimental grasslands.
AB  - Niche complementarity in resource use has been proposed as a key mechanism to
      explain the positive effects of increasing plant species richness on ecosystem
      processes, in particular on primary productivity. Since hardly any information is
      available for niche complementarity in water use, we tested the effects of plant
      diversity on spatial and temporal complementarity in water uptake in experimental
      grasslands by using stable water isotopes. We hypothesized that water uptake from
      deeper soil depths increases in more diverse compared to low diverse plant
      species mixtures. We labeled soil water in 8 cm (with 18O) and 28 cm depth (with
      2H) three times during the 2011 growing season in 40 temperate grassland
      communities of varying species richness (2, 4, 8 and 16 species) and functional
      group number and composition (legumes, grasses, tall herbs, small herbs). Stable
      isotope analyses of xylem and soil water allowed identifying the preferential
      depth of water uptake. Higher enrichment in 18O of xylem water than in 2H
      suggested that the main water uptake was in the upper soil layer. Furthermore,
      our results revealed no differences in root water uptake among communities with
      different species richness, different number of functional groups or with time.
      Thus, our results do not support the hypothesis of increased complementarity in
      water use in more diverse than in less diverse communities of temperate grassland
      species. 

PMID- 25587999
TI  - Electrostatic interaction between nonuniformly charged colloids: experimental and
      numerical study.
AB  - The influence of the surface charge distribution on the interaction between
      nanosized particles in water is reported. The distribution of charges at the
      surface of initially neutral microemulsion droplets has been modulated by
      additions of various oligomeric cationic surfactants. The osmotic compressibility
      of the doped microemulsions was measured by light and small-angle neutrons
      scattering and reveals that the overall effective interaction induced by the
      ionic groups is repulsive. However, particular charge distributions decrease the
      osmotic compressibility much less than others. Independent measurements of the
      activity of the bromide counterions with specific electrodes evidence a
      significant decrease in the effective charge, which, however, cannot account for
      the osmotic compressibility in the framework of the primitive model. The q
      dependence of the structure factor reveals an attractive contribution over a
      short distance. Numerical studies assign this attractive contribution to the
      overlap of hydration shells that are extended as a result of the charge
      localization. 

PMID- 25588001
TI  - Development of a Veterans Affairs hybrid operating room for transcatheter aortic
      valve replacement in the cardiac catheterization laboratory.
AB  - IMPORTANCE: Transcatheter aortic valve replacement (TAVR) revolutionized the
      treatment of aortic stenosis. Developing a TAVR program with a custom-built
      hybrid operating room (HOR) outside the surgical operating room area poses unique
      challenges in Veterans Affairs (VA) institutions. OBJECTIVE: To present the
      process by which the San Francisco VA Medical Center developed a VA-approved TAVR
      program, in which an HOR exists in a cardiac catheterization laboratory, as a
      guideline for future programs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
      review of each required approval process for developing an HOR in a cardiac
      catheterization laboratory in a VA designated for complex surgery. Participants
      included San Francisco VA Medical Center health care professionals and
      individuals responsible for new program initiation in VA institutions. EXPOSURES:
      External reviews by industry vendors, the VA Central Office, and the Office for
      Construction, Facilities, and Management and an internal Healthcare Failure Mode
      and Effect Analysis. MAIN OUTCOMES AND MEASURES: The timeline for each process.
      RESULTS: Developing a TAVR program required vetting and approval from industry
      vendors, who provided training and expertise. Architectural plans for
      construction of the HOR began in 2010-2011, followed by approval from Edwards
      Lifesciences, Inc, in 2012 and fundamentals training on February 8 and 9, 2013.
      Following a pilot launch of the first VA TAVR program at the Houston VA Medical
      Center, subsequent programs were required to submit a plan to the VA Central
      Office for proposed restructuring of their clinical programs. After the San
      Francisco VA Medical Center proposal submission on February 3, 2013, a site visit
      consisting of a National Chief of Catheterization Laboratory Managers, a cardiac
      surgeon, and an interventional cardiologist with TAVR experience was conducted on
      April 12, 2013. During construction, HOR plans were inspected by the Office for
      Construction, Facilities, and Management followed by on-site inspection on August
      8, 2013, to assess the adequacy of the HOR, newly built restricted corridors,
      equipment storage areas, and altered staff and patient flow patterns. Last, a
      Healthcare Failure Mode and Effect Analysis was performed to mitigate any
      negative effects of the HOR not being colocated in the surgical operating room
      area. Approval was then granted on November 13, 2013. Our first 10 TAVR cases
      were successfully completed as of April 2, 2014. CONCLUSIONS AND RELEVANCE: The
      primary factor for development of a successful TAVR program is integration of the
      heart valve team. Particular adaptations to the cardiac catheterization
      laboratory environment are required to accommodate an uncompromised HOR in which
      cardiac and vascular surgeons can be as comfortable as their interventional
      cardiology colleagues.

PMID- 25588000
TI  - Laterality across languages: Results from a global dichotic listening study using
      a smartphone application.
AB  - Left-hemispheric language dominance has been suggested by observations in
      patients with brain damages as early as the 19th century, and has since been
      confirmed by modern behavioural and brain imaging techniques. Nevertheless, most
      of these studies have been conducted in small samples with predominantly Anglo
      American background, thus limiting generalization and possible differences
      between cultural and linguistic backgrounds may be obscured. To overcome this
      limitation, we conducted a global dichotic listening experiment using a
      smartphone application for remote data collection. The results from over 4,000
      participants with more than 60 different language backgrounds showed that left
      hemispheric language dominance is indeed a general phenomenon. However, the
      degree of lateralization appears to be modulated by linguistic background. These
      results suggest that more emphasis should be placed on cultural/linguistic
      specificities of psychological phenomena and on the need to collect more diverse
      samples. 

PMID- 25588002
TI  - Decreased plasma iron in Alzheimer's disease is due to transferrin desaturation.
AB  - Plasma iron levels are decreased in Alzheimer's disease (AD) and associated with
      an idiopathic anemia. We examined iron-binding plasma proteins from AD patients
      and healthy controls from the Australian Imaging, Biomarkers and Lifestyle (AIBL)
      Flagship Study of Ageing using size exclusion chromatography-inductively coupled
      plasma-mass spectrometry. Peak area corresponding to transferrin (Tf) saturation
      was directly compared to routine pathological testing. We found a significant
      decrease in transferrin-associated iron in AD that was missed by routine
      pathological tests of transferrin saturation, and that was able to discriminate
      between AD and controls. The AD cases showed no significant difference in
      transferrin concentration, only a decrease in total transferrin-bound iron. These
      findings support that a previously identified decrease in plasma iron levels in
      AD patients within the AIBL study is attributable to decreased loading of iron
      into transferrin, and that this subtle but discriminatory change is not observed
      through routine pathological testing. 

PMID- 25588003
TI  - Apparent increase of reported hemorrhagic disease in the midwestern and
      northeastern USA.
AB  - We investigated temporal and spatial trends in reporting of hemorrhagic disease
      (HD) in the midwestern and northeastern US using a 33-yr (1980-2012)
      questionnaire-based data set. This data set was supported by an additional 19 yr
      (1994-2012) of bluetongue virus (BTV) and epizootic hemorrhagic disease virus
      (EHDV) isolation results from clinically affected white-tailed deer (Odocoileus
      virginianus) in these regions. Both the number of counties that were reported
      positive for HD and the northern latitudinal range of reported HD increased with
      time. A similar increase was observed with both the number of states annually
      reporting HD and the number of counties where HD was reported. Large-scale
      outbreaks occurred in 1988, 1996, 2007, and 2012, and the scale of these
      individual outbreaks also increased with time. The predominant virus isolated
      from these regions was EHDV-2, but the prevalence of EHDV-6, which was first
      detected in 2006, appears to be increasing. Temporally, the extent of regional HD
      reporting was correlated with regional drought conditions. The significance of
      increases in reported HD and the incursions and establishment of new BTV and EHDV
      in the US currently are unknown.

PMID- 25588005
TI  - The prevalence and clinical significance of Chlamydia infection in island and
      mainland populations of Victorian koalas (Phascolarctos cinereus).
AB  - Chlamydia infection is known to impact the health of koalas (Phascolarctos
      cinereus) in New South Wales (NSW) and Queensland, but the clinical significance
      of Chlamydia infections in Victorian koalas is not well described. We examined
      the prevalence of Chlamydia infection and assessed associated health parameters
      in two Victorian koala populations known to be Chlamydia positive. The same
      testing regimen was applied to a third Victorian population in which Chlamydia
      had not been detected. We examined 288 koalas and collected samples from the
      urogenital sinus and conjunctival sacs. Detection and differentiation of
      Chlamydia species utilized real-time PCR and high-resolution melting curve
      analysis. Chlamydia pecorum was detected in two populations (prevalences: 25% and
      41%, respectively) but only from urogenital sinus swabs. Chlamydia was not
      detected in the third population. Chlamydia pneumoniae was not detected.
      Chlamydia pecorum infection was positively associated with wet bottom (indicating
      chronic urinary tract disease) in one Chlamydia-positive population and with
      abnormal urogenital ultrasound findings in the other Chlamydia-positive
      population. The prevalence of wet bottom was similar in all populations
      (including the Chlamydia-free population), suggesting there is another
      significant cause (or causes) of wet bottom in Victorian koalas. Ocular disease
      was not observed. This is the largest study of Chlamydia infection in Victorian
      koalas, and the results suggest the potential for epidemiologic differences
      related to Chlamydia infections between Victorian koalas and koalas in Queensland
      and NSW and also between geographically distinct Victorian populations. Further
      studies to investigate the genotypes of C. pecorum present in Victorian koalas
      and to identify additional causes of wet bottom in koalas are indicated. 

PMID- 25588006
TI  - Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free
      ranging prairie dogs (Cynomys spp.), Colorado, USA.
AB  - Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral
      sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN
      F1/V307) has been developed for prairie dogs. This vaccine is incorporated into
      palatable bait along with rhodamine B as a biomarker. We conducted trials in
      August and September 2012 to demonstrate uptake and apparent safety of the RCN
      F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging
      prairie dogs and other associated small rodents readily consumed vaccine-laden
      baits during field trials with no apparent adverse effects; most sampled prairie
      dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts
      of prairie dogs and their burrows revealed no evidence of prairie dog decline
      after vaccine exposure. No vaccine-related morbidity, mortality, or gross or
      microscopic lesions were observed. Poxviruses were not isolated from any animal
      sampled prior to bait distribution or on sites that received placebo baits. We
      isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus
      maniculatus) captured on sites where vaccine-laden baits were distributed. Based
      on these findings, studies examining the utility and effectiveness of oral
      vaccination to prevent plague-induced mortality in prairie dogs and associated
      species are underway. 

PMID- 25588007
TI  - Epidemiology and pathology of Toxoplasma gondii in free-ranging California sea
      lions (Zalophus californianus).
AB  - The coccidian parasite Toxoplasma gondii infects humans and warm-blooded animals
      worldwide. The ecology of this parasite in marine systems is poorly understood,
      although many marine mammals are infected and susceptible to clinical
      toxoplasmosis. We summarized the lesions associated with T. gondii infection in
      the California sea lion (Zalophus californianus) population and investigated the
      prevalence of and risk factors associated with T. gondii exposure, as indicated
      by antibody. Five confirmed and four suspected cases of T. gondii infection were
      identified by analysis of 1,152 medical records of necropsied sea lions from 1975
      2009. One suspected and two confirmed cases were identified in aborted fetuses
      from a sea lion rookery. Toxoplasmosis was the primary cause of death in five
      cases, including the two fetuses. Gross and histopathologic findings in T. gondii
      infected sea lions were similar to those reported in other marine mammals. The
      most common lesions were encephalitis, meningitis, and myocarditis. The antibody
      prevalence in stranded, free-ranging sea lions for 1998-2009 was 2.5% (+/-0.03%;
      IgG titer 640). There was an increase in odds of exposure in sea lions with
      increasing age, suggesting cumulative risk of exposure and persistent antibody
      over time. The occurrence of disseminated T. gondii infection in aborted fetuses
      confirms vertical transmission in sea lions, and the increasing odds of exposure
      with age is consistent with additional opportunities for horizontal transmission
      in free-ranging sea lions over time. These data suggest that T. gondii may have
      two modes of transmission in the sea lion population. Overall, clinical disease
      was uncommon in our study which, along with low prevalence of T. gondii antibody,
      suggests substantially less-frequent exposure and lower susceptibility to
      clinical disease in California sea lions as compared to sympatric southern sea
      otters (Enhydra lutris nereis). 

PMID- 25588008
TI  - Modeling the environmental growth of Pseudogymnoascus destructans and its impact
      on the white-nose syndrome epidemic.
AB  - White-nose syndrome (WNS) has had a devastating effect on North American bat
      populations. The causal agent of WNS is the fungal pathogen, Pseudogymnoascus
      destructans (Pd), which has been shown to persist in caves after the eradication
      of host populations. As nonpathogenic Pseudogymnoascus spp. display saprophytic
      growth and are among the most commonly isolated fungi from caves, we examined
      whether Pd could grow in cave sediments and the contribution such growth could
      have to WNS disease progression. We inoculated a range of diverse cave sediments
      and demonstrated the growth of Pd in all sediments tested. These data indicate
      that environmental growth of Pd could lead to the accumulation of spores above
      the estimated infection threshold for WNS, allowing environment-to-bat infection.
      The obtained growth parameters were then used in a susceptible-infected
      susceptible mathematic model to determine the possible contribution of
      environmental Pd growth to WNS disease progression in a colony of little brown
      bats (Myotis lucifugus). This model suggests that the environmental growth of Pd
      would increase WNS infection rates, particularly in colonies experiencing longer
      hibernation periods or in hibernacula with high levels of organic detritus. The
      model also suggests that once introduced, environmental Pd growth would allow the
      persistence of this pathogen within infected hibernacula for decades, greatly
      compromising the success of bat reintroduction strategies. Together these data
      suggest that Pd is not reliant on its host for survival and is capable of
      environmental growth and amplification that could contribute to the rapid
      progression and long-term persistence of WNS in the hibernacula of threatened
      North American bats. 

PMID- 25588009
TI  - Prevalence of the generalist flea Pulex simulans on black-tailed prairie dogs
      (Cynomys ludovicianus) in New Mexico, USA: the importance of considering
      imperfect detection.
AB  - If a parasite is not detected during a survey, one of two explanations is
      possible: the parasite was truly absent or it was present but not detected. We
      fit occupancy models to account for imperfect detection when combing fleas
      (Siphonaptera) from black-tailed prairie dogs (Cynomys ludovicianus) during June
      August 2012 in the Vermejo Park Ranch, New Mexico, USA. With the use of detection
      histories from combing events during monthly trapping sessions, we fit occupancy
      models for two flea species: Oropsylla hirusta (a prairie dog specialist) and
      Pulex simulans (a generalist). Detection probability was <100% for both species
      and about 21% lower for P. simulans. Pulex simulans may be especially difficult
      to detect because it is about half the size of O. hirusta. Monthly occupancy
      (prevalence) for P. simulans was estimated at 24% (June, 95% confidence interval
      = 19-30), 39% (July, 32-47), and 56% (August, 49-64) in new prairie dog colonies,
      and 43% (32-54), 61% (49-71), and 79% (70-87) in old colonies. These results
      suggest P. simulans can attain high prevalence on prairie dogs, especially in old
      colonies. If P. simulans is highly prevalent on prairie dogs, it may serve as a
      "bridge vector" between Cynomys and other mammalian hosts of the plague bacterium
      Yersinia pestis, and even function as a reservoir of Y. pestis between outbreaks.

PMID- 25588010
TI  - Experimental susceptibility of wood ducks (Aix sponsa) for West Nile virus.
AB  - Detection of West Nile virus (WNV) has been reported in a variety of wild ducks
      in the US, but little is known about the pathogenesis and outcome of exposure of
      the disease in these species. Previous experimental studies of WNV in ducks
      either have challenged a small number of ducks with WNV or have tested
      domesticated ducks. To determine susceptibility and immune response, we
      challenged 7-wk-old Wood Ducks (Aix sponsa) with a 1999 American Crow (Corvus
      brachyrhynchos) isolate of WNV. Wood Ducks were susceptible to infection with the
      virus, and, although clinical signs or mortality were not observed, microscopic
      lesions were noted, particularly in the heart and brain. West Nile virus viremia
      peaked on day 2 postinfection (pi) at 10(4.54) plaque-forming units (PFU) of
      virus/mL serum and WNV was shed orally (between 10(2) and 10(2.9) PFU per swab)
      and cloacally. Specific anti-WNV antibody response was rapid, with anti-WNV IgM
      detected on day 3 pi followed on day 5 pi by anti-WNV IgG. Neutralizing
      antibodies were detected by plaque-reduction neutralization assay in one duck on
      day 4 pi, and in all sampled ducks on day 5. These results indicate that Wood
      Ducks are susceptible to WNV, but it is unlikely that significant WNV mortality
      events occur in Wood Ducks or that they play a significant role in transmission.
      However, WNV viremia was sufficient, in theory, to infect mosquitoes, and oral
      and cloacal shedding of the virus may increase the risk of infection to other
      waterbirds.

PMID- 25588011
TI  - Ichthyophonus sp. (Ichthyophonae, Ichthyophonida) infection in a South American
      amphibian, the hylid frog Hypsiboas pulchellus.
AB  - We report infection by Ichthyophonus sp. in a South American amphibian, the hylid
      frog Hypsiboas pulchellus in Uruguay. This frog had a large subcutaneous mass
      over the urostyle and dorsal musculature comprised of parasitic cysts with mild
      granulomatous inflammation but otherwise appeared healthy. 

PMID- 25588012
TI  - Surveillance and characterization of Riemerella anatipestifer from wild birds in
      South Korea.
AB  - We conducted surveillance for Riemerella anatipestifer (RA) in wild birds along
      the East Asian-Australasian flyway in South Korea. Detected RA were characterized
      by serotype, antibiotic susceptibility, and sequence analysis of the 16S rRNA
      gene. We collected 944 wild birds of 34 species from 19 of South Korea's major
      migratory wild bird habitats between 2011 and 2012. We identified RA by PCR and
      rRNA gene sequence in 71/102 (69.6%) pharyngeal swabs and 19/944 (2.0%) cloacal
      swabs of wild birds. Most RA positives (71/75 [95%] pharyngeal and 19/704 [(2.6%]
      cloacal) were from three duck species (family Anatidae): Mallard Duck (Anas
      platyrhynchos), Northern Pintail (Anas acuta), and Spot-billed Duck (Anas
      poecilorhyncha). Thirty-three RA isolates obtained and examined were highly
      resistant to aminoglycosides: kanamycin (100%), gentamicin (94%), amikacin (91%),
      neomycin (88%), and streptomycin (82%). Six isolates were identified as serotype
      4 by agar gel precipitation. Serotypes 1 and 7, which are known virulent
      serotypes, were also identified in three isolates from wild duck species. 

PMID- 25588013
TI  - Influence of ecologic factors on prevalence of meningeal worm
      (Parelaphostrongylus tenuis) infection in South Dakota, USA.
AB  - The meningeal worm (Parelaphostrongylus tenuis) is a nematode parasite that
      commonly infects white-tailed deer (Odocoileus virginianus; WTD) throughout the
      deciduous forest biome and deciduous-coniferous ecotone of eastern and central
      North America; the species is not known to occur west of the grassland biome of
      central North America. We used county-specific prevalence data to evaluate
      potential effects of landscape and climatologic factors on the spatial
      distribution of meningeal worm infection in South Dakota, US. Probability of
      infection increased 4-fold between eastern and western South Dakota and 1.3-fold
      for each 1-cm increase in summer precipitation. Sixty-three percent of WTD had
      only a single worm in the cranium. Expansion of meningeal worm infection across
      western South Dakota may be inherently low due to the combined effects of arid
      climate and potential attributes of the Missouri River that limit regional
      movements by infected WTD. Use of landscape genetic analyses to identify
      potential relationships between landscape features and population genetic
      structure of infected deer and parasites may contribute to a greater
      understanding of regional heterogeneity in meningeal worm infection rates across
      South Dakota, particularly in counties adjacent to the Missouri River. Future
      research evaluating heterogeneity in prevalence and intensity of infection
      between fawn and yearling deer, and the potential role of yearling male deer as
      dispersal agents of meningeal worms across the Missouri River, also is warranted.

PMID- 25588014
TI  - Chemical immobilization of free-ranging fallow deer (Dama dama): effect of needle
      length on induction time.
AB  - We evaluated impact of the needle length, sex, and body condition on chemical
      immobilization induction time in 50 (29 males and 21 females) free-ranging fallow
      deer (Dama dama) in Sweden, 2006-11. Induction time is probably the single most
      important factor when immobilizing free-ranging wildlife with the use of a remote
      drug-delivery system. Induction times should be short to minimize stress and risk
      of injury, and to ensure that immobilized animals can be found and clinically
      monitored as soon as possible. We measured the distance between the darting
      location and where we recovered the immobilized animal and also the time
      occurring between the two events. We used two types of needles: 2.0 * 30- or 2.0
      * 40-mm barbed needles with side ports. The most important result is that a 10-mm
      longer dart needle can reduce the retrieval time substantially (>20 min) until an
      animal is under monitoring. On average after the darting, the retrieval time
      decreased from 51 to 29 min and the distance decreased from 519 m from the
      darting location to 294 m. We suggest that a needle length of 40 mm is preferable
      for immobilization of wild fallow deer, especially for animals in over-average-to
      fat body condition.

PMID- 25588015
TI  - Norwegian words: A lexical database for clinicians and researchers.
AB  - All words have properties linked to form, meaning and usage patterns which
      influence how easily they are accessed from the mental lexicon in language
      production, perception and comprehension. Examples of such properties are
      imageability, phonological and morphological complexity, word class, argument
      structure, frequency of use and age of acquisition. Due to linguistic and
      cultural variation the properties and the values associated with them differ
      across languages. Hence, for research as well as clinical purposes, language
      specific information on lexical properties is needed. To meet this need, an
      electronically searchable lexical database with more than 1600 Norwegian words
      coded for more than 12 different properties has been established. This article
      presents the content and structure of the database as well as the search options
      available in the interface. Finally, it briefly describes some of the ways in
      which the database can be used in research, clinical practice and teaching.

PMID- 25588016
TI  - Genomic characterisation of three Mapputta group viruses, a serogroup of
      Australian and Papua New Guinean bunyaviruses associated with human disease.
AB  - The Mapputta serogroup tentatively contains the mosquito-associated viruses
      Mapputta, Maprik, Trubanaman and Gan Gan. Interestingly, this serogroup has
      previously been associated with an acute epidemic polyarthritis-like illness in
      humans; however, there has been no ensuing genetic characterisation. Here we
      report the complete genome sequences of Mapputta and Maprik viruses, and a new
      Mapputta group candidate, Buffalo Creek virus, previously isolated from
      mosquitoes and detected by serology in a hospitalised patient. Phylogenetic
      analyses indicate that the group is one of the earliest diverged groups within
      the genus Orthobunyavirus of the family Bunyaviridae. Analyses show that these
      three viruses are related to the recently sequenced Australian bunyaviruses from
      mosquitoes, Salt Ash and Murrumbidgee. A notable feature of the Mapputta group
      viruses is the absence of the NSs (non-structural) ORF commonly found on the S
      segment of other orthobunyaviruses. Viruses of the Mapputta group have been
      isolated from geographically diverse regions ranging from tropical Papua New
      Guinea to the semi-arid climate of south-eastern Australia. The relevance of this
      group to human health in the region merits further investigation. 

PMID- 25588018
TI  - Novel psychoactive substances (designer drugs): overview and pharmacology of
      modulators of monoamine signaling.
AB  - Novel psychoactive substances are newly used designer drugs ("internet drugs",
      "research chemicals", "legal highs") potentially posing similar health risks to
      classic illicit substances. Chemically, many novel psychoactive substances can be
      classified as phenethylamines, amphetamines, synthetic cathinones, piperazines,
      pipradrols/piperidines, aminoindanes benzofurans, and tryptamines.
      Pharmacologically, these substances interact with various monoaminergic targets.
      Typically, stimulants inhibit the transport of dopamine and noradrenaline
      (pipradrols, pyrovalerone cathinones) or induce the release of these monoamines
      (amphetamines and methamphetamine-like cathinones), entactogens predominantly
      enhance serotonin release (phenylpiperazines, aminoindanes, para-substituted
      amphetamines, and MDMA-like cathinones) similar to MDMA (ecstasy), and
      hallucinogens (tryptamines, hallucinogenic phenethylamines) are direct agonists
      at serotonergic 5-HT2A receptors. Synthetic cannabinoids are another group of
      novel substances which all act as agonists at the cannabinoid CB1 receptor
      similar to THC but are chemically diverse. In particular, the relative
      serotonergic vs dopaminergic activity (determined by the dopamine/serotonin
      transporter inhibition ratio in vitro) can be helpful to predict the desired
      psychotropic but also the toxic effects of novel substances as well as their
      potential for addiction. Although the use of novel psychoactive substances mostly
      produces minor or moderate poisonings, serious complications occur. Serotonergic
      drugs (entactogens and hallucinogens) are associated with acute serotonin
      syndrome, hyperthermia, seizures, and hyponatremia. Dopaminergic drugs are highly
      addictive and acute toxicity includes prolonged stimulation, insomnia, agitation,
      and psychosis. Agitation, anxiety, paranoia, hypertension, and rarely myocardial
      infarction and renal failure are seen with synthetic cannabinoids. Treatment is
      supportive. 

PMID- 25588017
TI  - FTIR metabolomic fingerprint reveals different modes of action exerted by
      structural variants of N-alkyltropinium bromide surfactants on Escherichia coli
      and Listeria innocua cells.
AB  - Surfactants are extremely important agents to clean and sanitize various
      environments. Their biocidal activity is a key factor determined by the
      interactions between amphiphile structure and the target microbial cells. The
      object of this study was to analyze the interactions between four structural
      variants of N-alkyltropinium bromide surfactants with the Gram negative
      Escherichia coli and the Gram positive Listeria innocua bacteria. Microbiological
      and conductometric methods with a previously described FTIR bioassay were used to
      assess the metabolomic damage exerted by these compounds. All surfactants tested
      showed more biocidal activity in L. innocua than in E. coli. N
      tetradecyltropinium bromide was the most effective compound against both species,
      while all the other variants had a reduced efficacy as biocides, mainly against
      E. coli cells. In general, the most prominent metabolomic response was observed
      for the constituents of the cell envelope in the fatty acids (W1) and amides (W2)
      regions and at the wavenumbers referred to peptidoglycan (W2 and W3 regions).
      This response was particularly strong and negative in L. innocua, when cells were
      challenged by N-tetradecyltropinium bromide, and by the variant with a smaller
      head and a 12C tail (N-dodecylquinuclidinium bromide). Tail length was critical
      for microbial inhibition especially when acting against E. coli, maybe due the
      complex nature of Gram negative cell envelope. Statistical analysis allowed us to
      correlate the induced mortality with the metabolomic cell response, highlighting
      two different modes of action. In general, gaining insights in the interactions
      between fine structural properties of surfactants and the microbial diversity can
      allow tailoring these compounds for the various operative conditions. 

PMID- 25588019
TI  - Experimental evidence of replica symmetry breaking in random lasers.
AB  - Spin-glass theory is one of the leading paradigms of complex physics and
      describes condensed matter, neural networks and biological systems, ultracold
      atoms, random photonics and many other research fields. According to this theory,
      identical systems under identical conditions may reach different states. This
      effect is known as replica symmetry breaking and is revealed by the shape of the
      probability distribution function of an order parameter named the Parisi overlap.
      However, a direct experimental evidence in any field of research is still
      missing. Here we investigate pulse-to-pulse fluctuations in random lasers, we
      introduce and measure the analogue of the Parisi overlap in independent
      experimental realizations of the same disordered sample, and we find that the
      distribution function yields evidence of a transition to a glassy light phase
      compatible with a replica symmetry breaking. 

PMID- 25588020
TI  - Shelf-life of E-lysyl-3-(trimethylstannyl)benzamide immunoconjugates, precursors
      for 211At labeling of antibodies.
AB  - Astatine-211 is possibly the most promising radionuclide for targeted alpha
      particle therapy when it comes to the treatment of occult disseminated cancer.
      Preclinical research has proven effective, and patient studies have been
      initiated based on these results. However, a lack of production capacity and the
      complex radiochemistry of (211)At are major obstacles for research and
      prospective clinical applications. In the present study, astatination of
      immunoconjugates, already prepared well in advance before radiolabeling, was
      performed to investigate the possibility of formulating a kit-like reagent for
      the production of (211)At radiopharmaceuticals. The shelf-life of E-lysyl-3
      (trimethylstannyl)benzamide immunoconjugates was evaluated, that is, the effect
      of different storage times on the quality of the immunoconjugates. The quality
      being referred to is the capacity to maintain a good radiochemical yield and good
      cell-binding property after labeling with (211)At. The stability of the
      conjugates was found to be pH dependent with high stability at pH>=7 and less
      stability at pH<=5.5. The immunoconjugates (based on trastuzumab) could be kept
      for more than 3 months in a phosphate buffered saline solution (pH 7.4) at 4
      degrees C before labeling, without compromising the quality of the labeled
      product. The conjugates are also unaffected by storage at -20 degrees C.
      Conjugates with a good shelf-life compatible with distant shipping as well as
      improved radiochemistry are important steps to facilitate further clinical
      progress with (211)At. 

PMID- 25588021
TI  - Adherence to transfusion guidelines: are we prepared for the Smarter Medicine or
      Choosing Wisely initiative?
AB  - OBJECTIVE: To determine, whether a restrictive transfusion strategy is followed
      in our hospital and to identify differences in activities within departments and
      patient groups. METHOD: Over a period of 15 months, RBC transfusions were
      prospectively recorded including the haemoglobin level prior to transfusion and
      were grouped in the different departments of our hospital (internal medicine
      ward, department of surgery, emergency room, intensive care unit, gynaecology
      ward, medical outpatient clinic and oncology outpatient clinic). Indications and
      co-morbidities were assessed retrospectively by reviewing the patient's charts.
      RESULTS: There were 1,832 RBC products transfused in total. The overall mean
      level of haemoglobin before transfusion was 7.61 g/dl (+/-1.1). These haemoglobin
      levels differed significantly between the departments (p <0.001), with the lowest
      threshold in the internal medicine ward (7.30 g/dl +/- 1.0) compared to the
      surgery ward (7.73 g/dl +/- 1.0) and to the intensive care unit (7.82 g/dl +/-
      0.9). In general, mean pre-transfusion haemoglobin levels did not differ
      significantly between patients with coronary artery disease (CAD) and patients
      without (7.64 g/dl +/- 1.0 vs 7.59 g/dl +/- 1.1, p = 0.48). In transfusions for
      patients with acute coronary syndrome a tendency to a higher transfusion
      threshold than in patients with stable CAD could be found (7.84 g/dl +/- 0.7 vs
      7.58 g/dl +/- 1.0, p = 0.05). Patients with haematological disorders were
      transfused at a higher threshold when compared to patients without (7.77 g/dl vs
      7.56 g/dl, p = 0.006). CONCLUSION: All wards in our analysis are following the
      current guidelines based on restrictive transfusion strategies. At the same time,
      we were able to detect significant differences between different departments and
      patient characteristics.

PMID- 25588022
TI  - Three- and four-class classification models for P-glycoprotein inhibitors using
      counter-propagation neural networks.
AB  - P-glycoprotein (P-gp) is an ATP binding cassette (ABC) transporter that helps to
      protect several certain human organs from xenobiotic exposure. This efflux pump
      is also responsible for multi-drug resistance (MDR), an issue of the chemotherapy
      approach in the fight against cancer. Therefore, the discovery of P-gp inhibitors
      is considered one of the most popular strategies to reverse MDR in tumour cells
      and to improve therapeutic efficacy of commonly used cytotoxic drugs. Until now,
      several generations of P-gp inhibitors have been developed but they have largely
      failed in preclinical and clinical studies due to lack of selectivity, poor
      solubility and severe pharmacokinetic interactions. In this study, three models
      (SION, SIO, SIN) to classify specific 'true' P-gp inhibitors as well as three
      other models (CPBN, CPB1, CPN) to distinguish between P-gp inhibitors, CYP 3A
      inhibitors and co-inhibitors of these proteins with rather high accuracy values
      for the test set and the external set were generated based on counter-propagation
      neural networks (CPG-NN). Such three and four-class classification models helped
      provide more information about the bioactivities of compounds not only on one
      target (P-gp), but also on a combination of multiple targets (P-gp, CYP 3A). 

PMID- 25588023
TI  - [Cough as a rare symptom of a pacemaker lead perforation].
AB  - Cough is a common symptom in respiratory medicine. We report on a 60-year-old
      patient, who developed cough after pacemaker implantation. Diagnostic work up
      yielded malposition of the right-ventricular lead with penetration of the
      myocardium. Revision of the lead resulted in complete cessation of cough.
      CONCLUSION: Pacemaker dysfunction and/or malposition of pacemaker lead should be
      considered in differential diagnosis of cough after pacemaker implantation.

PMID- 25588024
TI  - Fusobacterium nucleatum endocarditis presenting as liver and brain abscesses in
      an immunocompetent patient.

PMID- 25588025
TI  - Global establishment risk of economically important fruit fly species
      (Tephritidae).
AB  - The global invasion of Tephritidae (fruit flies) attracts a great deal of
      attention in the field of plant quarantine and invasion biology because of their
      economic importance. Predicting which one in hundreds of potential invasive fruit
      fly species is most likely to establish in a region presents a significant
      challenge, but can be facilitated using a self organising map (SOM), which is
      able to analyse species associations to rank large numbers of species
      simultaneously with an index of establishment. A global presence/absence dataset
      including 180 economically significant fruit fly species in 118 countries was
      analysed using a SOM. We compare and contrast ranked lists from six countries
      selected from each continent, and also show that those countries geographically
      close were clustered together by the SOM analysis because they have similar fruit
      fly assemblages. These closely clustered countries therefore represent greater
      threats to each other as sources of invasive fruit fly species. Finally, we
      indicate how this SOM method could be utilized as an initial screen to support
      prioritizing fruit fly species for further research into their potential to
      invade a region. 

PMID- 25588026
TI  - The heterogeneity of socially isolated older adults: a social isolation typology.
AB  - Recent statistics show a growing number of older adults who are living alone and
      are socially isolated. It is against this background that, in recent years, many
      interventions have been developed to address social isolation among the elderly.
      Evaluative studies show that most interventions are hardly effective, though. An
      important reason for this is the heterogeneity of the socially isolated. This
      article offers insight into this heterogeneity by presenting a typology with
      different profiles of socially isolated older adults and the intervention
      implications of this typology. The typology is derived from an extensive
      qualitative study on socially isolated elderly individuals in the Netherlands.
      The typology imposes some degree of order to a diversity of circumstances,
      ambitions, and possibilities of the socially isolated elderly, thereby deepening
      the understanding of the heterogeneity of this population. The definition of
      social isolation used in this study starts from a societal angle of incidence,
      namely the current policy context of Western European welfare states, in which
      governments emphasize the importance of independence and self-reliance of their
      citizens. Developed from that perspective, the typology provides a theoretical
      basis for applying interventions aimed at increasing self-reliance of social
      isolated elderly. This perspective on social isolation also has consequences for
      the way in which the effectiveness of interventions to alleviate social isolation
      is assessed. 

PMID- 25588027
TI  - Reactivity of the [M(PS)2](+) building block (M = Re(III) and (99m)Tc(III); PS =
      phosphinothiolate) toward isopropylxanthate and pyridine-2-thiolate.
AB  - The coordination properties of isopropylxanthate (i-Pr-Tiox) and pyridine-2
      thiolate (PyS) toward the [M(PS)2](+) moiety (M = Re and (99m)Tc; PS =
      phosphinothiolate) were investigated. Synthesis and full characterization of
      [Re(PS2)2(i-Pr-Tiox)] (Re1), [Re(PSiso)2(i-Pr-Tiox)] (Re2), [Re(PS2)2(PyS)]
      (Re3), and [Re(PSiso)2(PyS)] (Re4), where PS2 = 2
      (diphenylphosphino)ethanethiolate and PSiso = 2
      (diisopropylphosphino)ethanethiolate, and the structural X-ray analysis of
      complex Re3 were carried out. (99m)Tc analogues of complexes Re2 ((99m)Tc2) and
      Re4 ((99m)Tc4) were obtained in high radiochemical yield following a simple one
      pot procedure. The chemical identity of the radiolabeled compounds was confirmed
      by chromatographic comparison with the corresponding rhenium complexes and by
      dual radio/UV HPLC analysis combined with ESI(+)-MS of (99g/99m)Tc complexes
      prepared in carrier-added conditions. The two radiolabeled complexes were stable
      with regard to trans chelation with cysteine, glutathione, and
      ethylenediaminotetraacetic acid and in rat and human sera. This study highlights
      the substitution-inert metal-fragment behavior of the [M(PS)2](+) framework,
      which reacts with suitable bidentate coligands to form stable hexacoordinated
      asymmetrical complexes. This feature makes it a promising platform on which to
      develop a new class of Re/Tc complexes that are potentially useful in
      radiopharmaceutical applications. 

PMID- 25588028
TI  - Optical drug monitoring: photoacoustic imaging of nanosensors to monitor
      therapeutic lithium in vivo.
AB  - Personalized medicine could revolutionize how primary care physicians treat
      chronic disease and how researchers study fundamental biological questions. To
      realize this goal, we need to develop more robust, modular tools and imaging
      approaches for in vivo monitoring of analytes. In this report, we demonstrate
      that synthetic nanosensors can measure physiologic parameters with photoacoustic
      contrast, and we apply that platform to continuously track lithium levels in
      vivo. Photoacoustic imaging achieves imaging depths that are unattainable with
      fluorescence or multiphoton microscopy. We validated the photoacoustic results
      that illustrate the superior imaging depth and quality of photoacoustic imaging
      with optical measurements. This powerful combination of techniques will unlock
      the ability to measure analyte changes in deep tissue and will open up
      photoacoustic imaging as a diagnostic tool for continuous physiological tracking
      of a wide range of analytes. 

PMID- 25588029
TI  - Guardian small RNAs and sex determination.
AB  - The W chromosome of the silkworm Bombyx mori has been known to determine
      femaleness for more than 80 years. However, the feminizing gene has not been
      molecularly identified, because the B. mori W chromosome is almost fully occupied
      by a large number of transposable elements. The W chromosome-derived feminizing
      factor of B. mori was recently shown to be a female-specific PIWI-interacting RNA
      (piRNA). piRNAs are small RNAs that potentially repress invading "non-self"
      elements (e.g., transposons and virus-like elements) by associating with PIWI
      proteins. Our results revealed that female-specific piRNA precursors, which we
      named Fem, are transcribed from the sex-determining region of the W chromosome at
      the early embryonic stage and are processed into a single mature piRNA (Fem
      piRNA). Fem piRNA forms a complex with Siwi (silkworm Piwi), which cleaves a
      protein-coding mRNA transcribed from the Z chromosome. RNA interference of this Z
      linked gene, which we named Masc, revealed that this gene encodes a protein
      required for masculinization and dosage compensation. Fem and Masc both
      participate in the ping-pong cycle of the piRNA amplification loop by associating
      with the 2 B. mori PIWI proteins Siwi and BmAgo3 (silkworm Ago3), respectively,
      indicating that the piRNA-mediated interaction between the 2 sex chromosomes is
      the primary signal for the B. mori sex determination cascade. Fem is a non
      transposable repetitive sequence on the W chromosome, whereas Masc is a single
      copy protein-coding gene. It is of great interest how the piRNA system recognizes
      "self "Masc mRNA as "non-self" RNA. 

PMID- 25588030
TI  - Human-inspired sound environment recognition system for assistive vehicles.
AB  - OBJECTIVE: The human auditory system acquires environmental information under
      sound stimuli faster than visual or touch systems, which in turn, allows for
      faster human responses to such stimuli. It also complements senses such as sight,
      where direct line-of-view is necessary to identify objects, in the environment
      recognition process. This work focuses on implementing human reaction to sound
      stimuli and environment recognition on assistive robotic devices, such as robotic
      wheelchairs or robotized cars. These vehicles need environment information to
      ensure safe navigation. APPROACH: In the field of environment recognition, range
      sensors (such as LiDAR and ultrasonic systems) and artificial vision devices are
      widely used; however, these sensors depend on environment constraints (such as
      lighting variability or color of objects), and sound can provide important
      information for the characterization of an environment. In this work, we propose
      a sound-based approach to enhance the environment recognition process, mainly for
      cases that compromise human integrity, according to the International
      Classification of Functioning (ICF). Our proposal is based on a neural network
      implementation that is able to classify up to 15 different environments, each
      selected according to the ICF considerations on environment factors in the
      community-based physical activities of people with disabilities. MAIN RESULTS:
      The accuracy rates in environment classification ranges from 84% to 93%. This
      classification is later used to constrain assistive vehicle navigation in order
      to protect the user during daily activities. This work also includes real-time
      outdoor experimentation (performed on an assistive vehicle) by seven volunteers
      with different disabilities (but without cognitive impairment and experienced in
      the use of wheelchairs), statistical validation, comparison with previously
      published work, and a discussion section where the pros and cons of our system
      are evaluated. SIGNIFICANCE: The proposed sound-based system is very efficient at
      providing general descriptions of the environment. Such descriptions are focused
      on vulnerable situations described by the ICF. The volunteers answered a
      questionnaire regarding the importance of constraining the vehicle velocities in
      risky environments, showing that all the volunteers felt comfortable with the
      system and its performance.

PMID- 25588031
TI  - Public health interventions to control syphilis.
AB  - Syphilis control strategies are old, but interventions have changed and there is
      now a more scientific approach to evidence of effectiveness. We searched PubMed
      using 'syphilis control' to identify papers that measured the effectiveness of
      interventions. We also included novel approaches and comprehensive responses to
      outbreaks. Few papers used high-quality research methodology and fewer evaluated
      impact on prevalence or incidence; most assessed intermediate outcomes. Syphilis
      can often be controlled by a combination of case finding, treatment and
      education. However, outbreaks are unique and ongoing evaluation is needed to see
      if interventions are producing intended intermediate outcomes at reasonable
      costs. 

PMID- 25588032
TI  - Cost of abating greenhouse gas emissions with cellulosic ethanol.
AB  - We develop an integrated framework to determine and compare greenhouse gas (GHG)
      intensities and production costs of cellulosic ethanol derived from corn stover,
      switchgrass, and miscanthus grown on high and low quality soils for three
      representative counties in the Eastern United States. This information is
      critical for assessing the cost-effectiveness of utilizing cellulosic ethanol for
      mitigating GHG emissions and designing appropriate policy incentives to support
      cellulosic ethanol production nationwide. We find considerable variations in the
      GHG intensities and production costs of ethanol across feedstocks and locations
      mostly due to differences in yields and soil characteristics. As compared to
      gasoline, the GHG savings from miscanthus-based ethanol ranged between 130% and
      156% whereas that from switchgrass ranged between 97% and 135%. The corresponding
      range for GHG savings with corn stover was 57% to 95% and marginally below the
      threshold of at least 60% for biofuels classified as cellulosic biofuels under
      the Renewable Fuels Standard. Estimates of the costs of producing ethanol
      relative to gasoline imply an abatement cost of at least $48 Mg(-1) of GHG
      emissions (carbon dioxide equivalent) abated and can be used to infer the minimum
      carbon tax rate needed to induce consumption of cellulosic ethanol. 

PMID- 25588033
TI  - HIV infection, cardiovascular disease risk factor profile, and risk for acute
      myocardial infarction.
AB  - BACKGROUND: Traditional cardiovascular disease risk factors (CVDRFs) increase the
      risk of acute myocardial infarction (AMI) among HIV-infected (HIV+) participants.
      We assessed the association between HIV and incident AMI within CVDRF strata.
      METHODS: Cohort-81,322 participants (33% HIV+) without prevalent CVD from the
      Veterans Aging Cohort Study Virtual Cohort (prospective study of HIV+ and matched
      HIV- veterans) participated in this study. Veterans were followed from first
      clinical encounter on/after April 1, 2003, until AMI/death/last follow-up date
      (December 31, 2009). Predictors-HIV, CVDRFs (total cholesterol, cholesterol
      lowering agents, blood pressure, blood pressure medication, smoking, diabetes)
      used to create 6 mutually exclusive profiles: all CVDRFs optimal, 1+ nonoptimal
      CVDRFs, 1+ elevated CVDRFs, and 1, 2, 3+ major CVDRFs. Outcome-Incident AMI
      [defined using enzyme, electrocardiogram (EKG) clinical data, 410 inpatient ICD-9
      (Medicare), and/or death certificates]. Statistics-Cox models adjusted for
      demographics, comorbidity, and substance use. RESULTS: Of note, 858 AMIs (42%
      HIV+) occurred over 5.9 years (median). Prevalence of optimal cardiac health was
      <2%. Optimal CVDRF profile was associated with the lowest adjusted AMI rates.
      Compared with HIV- veterans, AMI rates among HIV+ veterans with similar CVDRF
      profiles were higher. Compared with HIV- veterans without major CVDRFs, HIV+
      veterans without major CVDRFs had a 2-fold increased risk of AMI (HR: 2.0; 95%
      confidence interval: 1.0 to 3.9; P = 0.044). CONCLUSIONS: The prevalence of
      optimal cardiac health is low in this cohort. Among those without major CVDRFs,
      HIV+ veterans have twice the AMI risk. Compared with HIV- veterans with high
      CVDRF burden, AMI rates were still higher in HIV+ veterans. Preventing/reducing
      CVDRF burden may reduce excess AMI risk among HIV+ people.

PMID- 25588034
TI  - Berberine ameliorates nonbacterial prostatitis via multi-target metabolic network
      regulation.
AB  - Metabolomics has been increasingly applied to discovering biomarkers and
      identifying perturbed pathways. Berberine has been shown to exhibit anti
      inflammatory, antioxidant, and anticancer properties, but its mechanisms for
      treating nonbacterial prostatitis (NBP) remain unclear completely. We developed
      the untargeted metabolomics approach based on UPLC-Q-TOF-HDMS to profile the
      metabolite changes in urine samples in order to discover novel potential
      biomarkers to clarify mechanisms of berberine in treating a rat model of
      capsaicin-induced nonbacterial prostatitis (NBP). The changes in metabolic
      profiling were restored to their base-line values after berberine treatment
      according to the principal component analysis (PCA) score plots. Fourteen
      different potential biomarkers and five acutely perturbed metabolic pathways
      contributing to the treatment of NBP were discovered and identified.
      Specifically, the berberine-treated rats are located closer to the normal group,
      indicating that the NBP-induced disturbances to the metabolic profile were
      partially reversed by berberine treatment. After treatment with berberine, the
      relative contents of 12 potential biomarkers were effectively regulated, which
      suggested that the therapeutic effects of berberine on NBP may involve regulating
      disturbances to the metabolism. Our results show that the protective effect of
      berberine occurs in part through a reversal of the NBP-caused disturbances. 

PMID- 25588035
TI  - Evaluation of the efficacy and safety of fractional bipolar radiofrequency with
      high-energy strategy for treatment of acne scars in Chinese.
AB  - BACKGROUND: Fractional technology overcomes several problems of ablative lasers
      such as a high incidence rate of post- inflammatory hyperpigmentation (PIH). A
      new technology fractional radiofrequency, which induces deep dermal heating and
      leaves the epidermal less affected results in less adverse effect in Chinese.
      OBJECTIVE: To evaluate the efficacy, safety and tolerance of fractional bipolar
      radiofrequency (RF) in the treatment of acne scars in Asian people with the
      strategy of high energy. METHODS: Twenty-six healthy Asian patients with acne
      scars received four monthly high energy (85-95mj/pin) treatments with a
      fractional bipolar RF device. Improvement and tolerance were evaluated at each
      treatment and a 4-week and 12-week follow-up visit. RESULTS: Twenty-three
      patients completed the study. Acne score showed a significantly decrease at 4
      week and 12-week follow-up visits. Patients' evaluation of global improvement and
      satisfaction increased at the 12-week visit compared with baseline. Side effects
      were limited to transient pain, erythema, dryness and low risk of PIH.
      CONCLUSION: Treatment with high energy of fractional bipolar RF is safe and
      effective for acne scars in Asian people. Common side effects such as PIH,
      eschars are less than fractional lasers.

PMID- 25588036
TI  - Allergic reaction to hyaluronidase use after hyaluronic acid filler injection.
AB  - Hyaluronic acid (HA) is biocompatible, easy to use and reversible. HA fillers are
      considered to be safe, although some complications can occur. At this time,
      hyaluronidase is used off-label for correction. A 41-year-old woman presented to
      our clinic for focal erythematous plaque on hyaluronidase injection site. She got
      the injection for correction of HA filler excess. The skin lesion continued for 7
      days. Histopathologic findings were nonspecific. On intradermal skin test,
      allergic reaction to hyaluronidase were confirmed. Adverse effects of this
      hyaluronidase are uncommon with local injection site reactions most frequently
      reported. Allergy to hyaluronidase should be included in the differential
      diagnosis when focal erythema and swelling occur after hyaluronidase injection. 

PMID- 25588037
TI  - Treatment of atrophic facial acne scars with fractional Er:Yag laser.
AB  - BACKGROUND: Acne scars are often a permanent disfiguring sequel of acne vulgaris.
      Although many treatment modalities are available, they are often non satisfactory
      for all patients. OBJECTIVE: To determine the effectiveness and safety of
      fractional 1540 nm erbium_glass laser treatment of facial acne scars in Iraqi
      patients. PATIENTS AND METHODS: Twenty one patients were enrolled in this
      prospective clinical study. Three sessions of the 1540 nm erbium glass laser were
      applied at 2-week intervals. The patients were assessed at 1, 3, and 6 months
      after the last session. The effect of treatment was assessed by objective
      (Sharquie scoring system for grading acne scarring and visual analog scale) and
      subjective (patient satisfaction) methods. RESULTS: Two patients were defaulted.
      Eleven patients (57.9%) showed improvement from moderate to mild grade, and no
      grade changes were detected in eight patients (42.1%). The mean score of the
      visual analog scale prior to treatment was 8.61 +/- 0.86 and decreased to 6.15 +/
      1.28 (P = 0.037). Ten patients were satisfied to varying degrees. No significant
      side effects were noted. CONCLUSION: Non-ablative fractional 1540 nm erbium glass
      laser is an effective and safe method to treat acne scars and represent good
      alternative for patients who cannot use the ablative methods because of its
      longer downtime.

PMID- 25588038
TI  - Verruca vulgaris: novel treatment with a 1064 nm Nd:YAG laser.
AB  - BACKGROUND: Verruca Vulgaris (VV) is common benign neoplasm. However, it can
      present a therapeutic challenge. Previous studies have suggested that the Nd-YAG
      laser may be beneficial in the management of warts. OBJECTIVE: To determine the
      effectiveness and safety of a novel 100 microsecond pulsed 1064 nm Nd:YAG laser
      for the treatment of VV. METHOD: A total of 25 adult subjects with a total of 63
      hand verrucae were enrolled in the clinical trial to receive treatment with a low
      energy (200 mjoule) 1064 nm Nd:YAG laser (PinPointe, NuvoLase, Inc.). Each
      subject was eligible for 3 treatments administered at monthly intervals. All
      verrucae were measured before each treatment session and at 6 months after the
      final treatment. RESULTS: A complete response was seen in 19 subjects and in 41
      verrucae. A complete response was defined as complete absence of verruca with the
      presence of normal skin dermatoglyphics. All other lesions showed at least
      partial response. A partial response was defined as a 50% or greater reduction in
      verruca size. No adverse events were noted. CONCLUSION: Low-energy 1064 nm Nd:
      YAG laser treatment may be a promising, safe, and effective therapeutic modality
      for the treatment of VV. However, more treatment sessions may be needed for
      complete clearance and increased efficacy in some subjects.

PMID- 25588039
TI  - A rapid tattoo removal technique using a combination of pulsed Er:YAG and Q
      Switched Nd:YAG in a split lesion protocol.
AB  - BACKGROUND: Tattoo removal has evolved over the years and though Q-switched laser
      is the 'workhorse' laser, it invariably requires multiple sittings, which are
      dependent on numerous factors, including the skin colour, location of the tattoo,
      age of the tattoo, colour of pigment used, associated fibrosis and the kind of
      tattoo treated. Though ablative lasers, both pulsed CO2 and Er:YAG, have been
      used for recalcitrant tattoos, very few studies have been done comparing them
      with pigment-specific lasers. Our study was based on the premise that ablating
      the epidermis overlying the tattoo pigment with Er:YAG could help in gaining
      better access to the pigment which would enable the Q-switched laser to work
      effectively with less beam scattering. OBJECTIVE: A study of rapid tattoo removal
      (RTR) technique using a combination of pulsed Er:YAG and Q-Switched Nd:YAG in a
      split lesion protocol. MATERIALS AND METHODS: This prospective study was
      undertaken during 2010-13 at a laser Clinic in the Maulana Azad Medical College,
      New Delhi. A total of 10 patients were recruited, 5 of amateur tattoo and 5 of
      professional tattoo. After informed consent each tattoo was arbitrarily 'split'
      into two parts. One part was treated with QS Nd:YAG laser(1064 nm) and the other
      part with Er:YAG laser immediately followed by the QS Nd:YAG. The laser
      treatments were repeated at 6-week intervals until the tattoo pigment had
      cleared. On the combination side in subsequent sittings only the QS Nd:YAG was
      used, to minimize repetitive ablation. To ensure consistency in the intervention
      methods a trained dermatologist who was independent of the treatment delivery
      randomly rated 10% of the procedures. RESULTS: The mean improvement achieved by
      the Q-switched laser (2.93) was less than the combination laser (3.85) side (p =
      0.001) and needed more sessions (3.8 vs. 1.6; p = 0.001). There was a
      statistically significant difference in the improvement on the combination side
      till the second session. On the combination side patients required a maximum of 2
      sessions, while the Q-switched laser required 3-5 sessions for appreciable
      lightening. CONCLUSION: From our study it was concluded that use of a pulsed
      ablative laser may help in rapid removal of tattoos in conjunction with QS lasers
      with minimal side effects and can be used as a RTR.

PMID- 25588040
TI  - The next-generation ALK inhibitors.
AB  - PURPOSE OF REVIEW: Crizotinib now is accepted as the standard first-line
      treatment of ALK-rearranged lung adenocarcinomas. To overcome the problem of
      crizotinib resistance, second-generation ALK inhibitors are in development. The
      aim of this review is to give an overview on the mechanisms behind crizotinib
      resistance and on the preclinical background and clinical development of these
      compounds. RECENT FINDINGS: Based on phase I/II data, ceritinib has gained
      accelerated FDA approval for the treatment of crizotinib-resistant ALK-rearranged
      lung cancer. The clinical development of alectinib has already reached phase III.
      With AP26113, ASP3026, TSR-011, X-396 and different heat shock protein 90
      inhibitors, several other compounds led to promising early trial results. The
      toxicity profile of these drugs seems manageable, although side-effects still
      require attention and optimized supportive care. SUMMARY: Second-generation ALK
      inhibitors have arrived as part of our daily clinical practice. Challenges for
      the future will be to find the optimal place for these new drugs within the
      treatment algorithms. To reach this goal, careful trial design with special
      emphasis on genetically defined, homogeneous patient populations is imperative.

PMID- 25588041
TI  - Cell cycle control as a promising target in melanoma.
AB  - PURPOSE OF REVIEW: This review highlights recent clinical developments in the
      therapeutic targeting of cell cycle control in melanoma with cyclin-dependent
      kinase inhibitors, checkpoint kinases, MDM2, MDM4 and p53 inhibitors. RECENT
      FINDINGS: The high prevalence of activating genetic aberrations along the p16
      INK4A:cyclinD-CDK4/6:RB pathway in melanoma and increasing evidence that
      alterations in this pathway are linked to melanomagenesis, make targeting the p16
      INK4A:cyclinD-CDK4/6:RB pathway in melanoma logical and highly attractive. The
      presence of elevated CDK4 activity appears to correlate with greater CDK4/6
      inhibitor therapeutic activity, whereas the loss of RB1 has been linked to CDK
      inhibitor resistance. Other novel compounds targeting cell cycle control via
      reactivating wild-type p53 and checkpoint kinases are also currently under
      investigation in melanoma. SUMMARY: Cell cycle control is a promising target in
      the management of melanoma with early data reporting therapeutic benefit with
      cyclin-dependent kinase inhibitors, MDM2, and p53 reactivation compounds. Many of
      these drugs have entered phase I and II clinical trial development. Preliminary
      data from these studies are discussed in this review along with future treatment
      strategies for maximizing treatment outcomes in advanced melanoma. VIDEO
      ABSTRACT: http://links.lww.com/COON/A12.

PMID- 25588044
TI  - A highly sensitive and flexible pressure sensor with electrodes and elastomeric
      interlayer containing silver nanowires.
AB  - The next-generation application of pressure sensors is gradually being extended
      to include electronic artificial skin (e-skin), wearable devices, humanoid
      robotics and smart prosthetics. In these advanced applications, high sensing
      capability is an essential feature for high performance. Although surface
      patterning treatments and some special elastomeric interlayers have been applied
      to improve sensitivity, the process is complex and this inevitably raises the
      cost and is an obstacle to large-scale production. In the present study a simple
      printing process without complex patterning has been used for constructing the
      sensor, and an interlayer is employed comprising elastomeric composites filled
      with silver nanowires. By increasing the relative permittivity, epsilonr, of the
      composite interlayer induced by compression at high nanowire concentration, it
      has been possible to achieve a maximum sensitivity of 5.54 kPa(-1). The
      improvement in sensitivity did not sacrifice or undermine the other features of
      the sensor. Thanks to the silver nanowire electrodes, the sensor is flexible and
      stable after 200 cycles at a bending radius of 2 mm, and exhibits outstanding
      reproducibility without hysteresis under similar pressure pulses. The sensor has
      been readily integrated onto an adhesive bandage and has been successful in
      detecting human movements. In addition to measuring pressure in direct contact,
      non-contact pressures such as air flow can also be detected. 

PMID- 25588045
TI  - A radiographic scoring system to assess healing in congenital pseudarthrosis of
      the tibia.
AB  - The aim of this study was to determine whether an established radiographic union
      scoring system for tibial fracture healing (RUST) is reliable when used in
      neurofibromatosis (NF1) patients with congenital pseudarthrosis of the tibia
      (CPT) treated by intramedullary fixation. Four individuals reviewed 36 sets of
      radiographs from 12 NF1 patients with CPT (preoperative, and 6 months and 1 year
      postoperative). Intraobserver reliability (kappa-value 0.89) and interobserver
      reliability (kappa-value 0.76) were high. The modified RUST scoring system is a
      useful tool when faced with the challenge of postoperative radiographic
      evaluation of the tibia in NF1 patients with CPT. 

PMID- 25588042
TI  - The baculovirus-expressed binding region of Plasmodium falciparum EBA-140 ligand
      and its glycophorin C binding specificity.
AB  - The erythrocyte binding ligand 140 (EBA-140) is a member of the Plasmodium
      falciparum DBL family of erythrocyte binding proteins, which are considered as
      prospective candidates for malaria vaccine development. The EBA-140 ligand is a
      paralogue of the well-characterized P. falciparum EBA-175 protein. They share
      homology of domain structure, including Region II, which consists of two
      homologous F1 and F2 domains and is responsible for ligand-erythrocyte receptor
      interaction during invasion. In this report we describe, for the first time, the
      glycophorin C specificity of the recombinant, baculovirus-expressed binding
      region (Region II) of P. falciparum EBA-140 ligand. It was found that the
      recombinant EBA-140 Region II binds to the endogenous and recombinant glycophorin
      C, but does not bind to Gerbich-type glycophorin C, neither normal nor
      recombinant, which lacks amino acid residues 36-63 of its polypeptide chain. Our
      results emphasize the crucial role of this glycophorin C region in EBA-140 ligand
      binding. Moreover, the EBA-140 Region II did not bind either to glycophorin D,
      the truncated form of glycophorin C lacking the N-glycan or to desialylated GPC.
      These results draw attention to the role of glycophorin C glycans in EBA-140
      binding. The full identification of the EBA-140 binding site on glycophorin C
      molecule, consisting most likely of its glycans and peptide backbone, may help to
      design therapeutics or vaccines that target the erythrocyte binding merozoite
      ligands. 

PMID- 25588046
TI  - The use of ultrasound in the management of septic arthritis of the hip.
AB  - In the assessment of septic arthritis of the hip in a pediatric population,
      ultrasound is a safe and easily conducted method to confirm an effusion. The need
      for MRI to further evaluate the patient for adjacent infection before treatment
      is debatable. Once an effusion is confirmed on ultrasonography, we have found
      that septic arthritis of the hip does not need advanced imaging before arthrotomy
      and debridement. Patients who fail to clinically respond to an initial hip
      arthrotomy and appropriate antibiotics may benefit from an MRI for the
      identification of concomitant infections that may require surgical intervention. 

PMID- 25588043
TI  - Ontology-based data integration between clinical and research systems.
AB  - Data from the electronic medical record comprise numerous structured but uncoded
      elements, which are not linked to standard terminologies. Reuse of such data for
      secondary research purposes has gained in importance recently. However, the
      identification of relevant data elements and the creation of database jobs for
      extraction, transformation and loading (ETL) are challenging: With current
      methods such as data warehousing, it is not feasible to efficiently maintain and
      reuse semantically complex data extraction and trans-formation routines. We
      present an ontology-supported approach to overcome this challenge by making use
      of abstraction: Instead of defining ETL procedures at the database level, we use
      ontologies to organize and describe the medical concepts of both the source
      system and the target system. Instead of using unique, specifically developed SQL
      statements or ETL jobs, we define declarative transformation rules within
      ontologies and illustrate how these constructs can then be used to automatically
      generate SQL code to perform the desired ETL procedures. This demonstrates how a
      suitable level of abstraction may not only aid the interpretation of clinical
      data, but can also foster the reutilization of methods for un-locking it.

PMID- 25588047
TI  - Deformity correction in pediatric skeletal dysplasia: treatment challenges and
      solutions.
AB  - We reviewed our experience with limb-deformity correction in 54 children with
      skeletal dysplasias. Our goal was to outline common treatment strategies
      developed in our hospital to overcome the challenges associated with the
      management of these conditions. Utilization of computer-assisted preoperative
      planning, intraoperative monitoring of peripheral nerve function, individualized
      bone segment stabilization using a modular circular external fixation system, and
      a flexible distraction protocol improved the precision of angular deformity
      correction in our practice, simplified external fixator assembly, diminished
      postoperative frame modifications, enhanced the stability of fixation, and
      reduced the rate of complications. 

PMID- 25588048
TI  - Tibial shaft fractures in adolescents: analysis of cast treatment successes and
      failures.
AB  - This study retrospectively analyzed cast treatment of 75 adolescent closed tibial
      diaphyseal fractures. The average age was 13.3 years (range, 10-17.4 years). Of
      the patients, 21% (16/75) required cast change/wedging in the clinic for loss of
      reduction, and three patients (4%, 3/75) injured in vehicular collisions had
      failure of cast treatment, requiring an unplanned surgical intervention. Initial
      and immediate postreduction radiographic deformities were greater (P<0.05) in
      patients who required cast change/wedging. Of the patients, 59% (44/75) required
      over 3 months of cast immobilization. Casting is successful in the majority of
      adolescent patients despite prolonged immobilization and the need for cast
      change/wedging. 

PMID- 25588049
TI  - Evaluation of complications of treatment of severe Blount's disease by circular
      external fixation using a novel classification scheme.
AB  - Corrective osteotomy for recalcitrant varus deformity secondary to adolescent and
      infantile Blount's disease can be challenging because of a combination of
      severity of deformity, complexity of deformity, and frequent association with
      patient obesity. We present here the outcome of treatment by osteotomy and
      gradual deformity correction by circular external fixation in 31 patients with
      either infantile or adolescent Blount's disease. We used a unique classification
      scheme to quantify and qualify complications in this patient group: category I,
      complications not requiring an alteration in the treatment plan, not involving
      unplanned return to surgery, and not influencing outcome; category II,
      complications requiring an alteration in the treatment plan, including unplanned
      returns to surgery, but that did not influence outcome; category IIIA,
      complications that resulted in a failure to achieve treatment goals; and category
      IIIB, complications that resulted in a failure to achieve treatment goals and the
      development of a new pathology or worsening of patient condition. All but one
      patient in this group incurred at least one complication. However, despite the
      complex nature of this patient population, 88% achieved satisfactory correction
      without developing category IIIA or IIIB complications. Careful selection of
      patients and vigilant postoperative management can result in excellent outcomes
      with circular external fixation and gradual correction in this challenging
      patient population. 

PMID- 25588050
TI  - Activation of G protein coupled estrogen receptor (GPER) promotes the migration
      of renal cell carcinoma via the PI3K/AKT/MMP-9 signals.
AB  - Renal cell carcinoma (RCC) is the third most frequent malignancy within
      urological oncology. However, the mechanisms responsible for RCC metastasis are
      still needed further illustration. Our present study revealed that a seven
      transmembrane receptor G-protein coupled estrogen receptor (GPER) was highly
      detected in various RCC cell lines such as ACHN, OS-RC-2 and SW839. The
      activation of GPER by its specific agonist G-1 significantly promoted the in
      vitro migration and invasion of ACHN and OS-RC-2 cells. G-1 also up regulated the
      expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. The inhibitor of MMP
      9 (Cat-444278), but not MMP-2 (Sc-204092), abolished G-1 induced cell migration,
      which suggested that MMP-9 is the key molecule mediating G-1 induced RCC
      progression. Further, G-1 treatment resulted in phosphorylation of AKT and ERK in
      RCC cells. PI3K/AKT inhibitor (LY294002), while not ERK inhibitor (PD98059),
      significantly abolished G-1 induced up regulation of MMP-9 in both AHCN and OS-RC
      2 cells. Generally, our data revealed that activation of GPER by its specific
      agonist G-1 promoted the metastasis of RCC cells through PI3K/AKT/MMP-9 signals,
      which might be a promising new target for drug discovery of RCC patients.

PMID- 25588051
TI  - Low-temperature polymorphic phase transition in a crystalline tripeptide L-Ala-L
      Pro-Gly.H2O revealed by adiabatic calorimetry.
AB  - We demonstrate application of precise adiabatic vacuum calorimetry to observation
      of phase transition in the tripeptide L-alanyl-L-prolyl-glycine monohydrate (APG)
      from 6 to 320 K and report the standard thermodynamic properties of the
      tripeptide in the entire range. Thus, the heat capacity of APG was measured by
      adiabatic vacuum calorimetry in the above temperature range. The tripeptide
      exhibits a reversible first-order solid-to-solid phase transition characterized
      by strong thermal hysteresis. We report the standard thermodynamic
      characteristics of this transition and show that differential scanning
      calorimetry can reliably characterize the observed phase transition with <5 mg of
      the sample. Additionally, the standard entropy of formation from the elemental
      substances and the standard entropy of hypothetical reaction of synthesis from
      the amino acids at 298.15 K were calculated for the studied tripeptide.

PMID- 25588052
TI  - Herpes simplex virus 1 Us3 deletion mutant is infective despite impaired capsid
      translocation to the cytoplasm.
AB  - Herpes simplex virus 1 (HSV-1) capsids are assembled in the nucleus bud at the
      inner nuclear membrane into the perinuclear space, acquiring envelope and
      tegument. In theory, these virions are de-enveloped by fusion of the envelope
      with the outer nuclear membrane and re-enveloped by Golgi membranes to become
      infective. Us3 enables the nucleus to cytoplasm capsid translocation.
      Nevertheless, Us3 is not essential for the production of infective progeny
      viruses. Determination of phenotype distribution by quantitative electron
      microscopy, and calculation per mean nuclear or cell volume revealed the
      following: (i) The number of R7041(?US3) capsids budding at the inner nuclear
      membrane was significantly higher than that of wild type HSV-1; (ii) The mean
      number of R7041(?US3) virions per mean cell volume was 2726, that of HSV-1
      virions 1460 by 24 h post inoculation; (iii) 98% of R7041(?US3) virions were in
      the perinuclear space; (iv) The number of R7041(?US3) capsids in the cytoplasm,
      including those budding at Golgi membranes, was significantly reduced. Cell
      associated R7041(?US3) yields were 2.37*10(8) and HSV-1 yields 1.57*10(8) PFU/mL
      by 24 h post inoculation. We thus conclude that R7041(?US3) virions, which
      acquire envelope and tegument by budding at the inner nuclear membrane into the
      perinuclear space, are infective.

PMID- 25588054
TI  - Emergency department visits by children and adolescents for antipsychotic drug
      adverse events.

PMID- 25588055
TI  - Synthetic chemically modified mrna-based delivery of cytoprotective factor
      promotes early cardiomyocyte survival post-acute myocardial infarction.
AB  - To extend the temporal window for cytoprotection in cardiomyocytes undergoing
      apoptosis after hypoxia and myocardial infarction (MI), a synthetic chemically
      modified mRNA (modRNA) was used to drive delivery of insulin-like growth factor-1
      (IGF1) within the area at risk in an in vivo murine model of MI. Delivery of IGF1
      modRNA, with a polyethylenimine-based nanoparticle, augmented secreted and cell
      associated IGF1, promoting cardiomyocyte survival and abrogating cell apoptosis
      under hypoxia-induced apoptosis conditions. Translation of modRNA-IGF1 was
      sufficient to induce downstream increases in the levels of Akt and Erk
      phosphorylation. Downregulation of IGF1 specific miRNA-1 and -133 but not miR-145
      expression was also confirmed. As a proof of concept, intramyocardial delivery of
      modRNA-IGF1 but not control modRNA-GFP significantly decreased the level of TUNEL
      positive cells, augmented Akt phosphorylation, and decreased caspase-9 activity
      within the infarct border zone 24 h post-MI. These findings demonstrate the
      potential for an extended cytoprotective effect of transient IGF1 driven by
      synthetic modRNA delivery. 

PMID- 25588056
TI  - Alternative one-pot synthesis of (trifluoromethyl)phenyldiazirines from
      tosyloxime derivatives: application for new synthesis of optically pure
      diazirinylphenylalanines for photoaffinity labeling.
AB  - Alternative one-pot synthesis of 3-(trifluoromethyl)-3-phenyldiazirine
      derivatives from corresponding tosyloximes is developed. The deprotonation of
      intermediate diaziridine by NH2(-) is a new approach for construction of
      diazirine. Moreover, a novel synthesis of optically pure
      (trifluoromethyl)diazirinylphenylalanine derivatives was attempted involving
      these methods. 

PMID- 25588053
TI  - KSHV reactivation and novel implications of protein isomerization on lytic switch
      control.
AB  - In Kaposi's sarcoma-associated herpesvirus (KSHV) oncogenesis, both latency and
      reactivation are hypothesized to potentiate tumor growth. The KSHV Rta protein is
      the lytic switch for reactivation. Rta transactivates essential genes via
      interactions with cofactors such as the cellular RBP-Jk and Oct-1 proteins, and
      the viral Mta protein. Given that robust viral reactivation would facilitate
      antiviral responses and culminate in host cell lysis, regulation of Rta's
      expression and function is a major determinant of the latent-lytic balance and
      the fate of infected cells. Our lab recently showed that Rta transactivation
      requires the cellular peptidyl-prolyl cis/trans isomerase Pin1. Our data suggest
      that proline-directed phosphorylation regulates Rta by licensing binding to Pin1.
      Despite Pin1's ability to stimulate Rta transactivation, unchecked Pin1 activity
      inhibited virus production. Dysregulation of Pin1 is implicated in human cancers,
      and KSHV is the latest virus known to co-opt Pin1 function. We propose that Pin1
      is a molecular timer that can regulate the balance between viral lytic gene
      expression and host cell lysis. Intriguing scenarios for Pin1's underlying
      activities, and the potential broader significance for isomerization of Rta and
      reactivation, are highlighted. 

PMID- 25588057
TI  - Mechanical platelet activation potential in abdominal aortic aneurysms.
AB  - Intraluminal thrombus (ILT) in abdominal aortic aneurysms (AAA) has potential
      implications to aneurysm growth and rupture risk; yet, the mechanisms underlying
      its development remain poorly understood. Some researchers have proposed that ILT
      development may be driven by biomechanical platelet activation within the AAA,
      followed by adhesion in regions of low wall shear stress. Studies have
      investigated wall shear stress levels within AAA, but platelet activation
      potential (AP) has not been quantified. In this study, patient-specific
      computational fluid dynamic (CFD) models were used to analyze stress-induced AP
      within AAA under rest and exercise flow conditions. The analysis was conducted
      using Lagrangian particle-based and Eulerian continuum-based approaches, and the
      results were compared. Results indicated that biomechanical platelet activation
      is unlikely to play a significant role for the conditions considered. No
      consistent trend was observed in comparing rest and exercise conditions, but the
      functional dependence of AP on stress magnitude and exposure time can have a
      large impact on absolute levels of anticipated platelet AP. The Lagrangian method
      obtained higher peak AP values, although this difference was limited to a small
      percentage of particles that falls below reported levels of physiologic
      background platelet activation. 

PMID- 25588060
TI  - Glutathione S-transferase M1/T1 genotype and melanoma in a Southern Italian
      population: a case-control study.
AB  - BACKGROUND: The aim of this study was to assess the frequency of GSTM1 and GSTT1
      null genotype in melanoma patients and controls from Sicily and Calabria, two
      regions of Southern Italy never investigated on this issue before, that present a
      peculiar gene pool because of their geographical and historical characteristics.
      METHODS: One hundred and twelve Caucasian melanoma patients and 150 age- and sex
      matched healthy controls were examined; their GSTM1/GSTT1 genotype was defined by
      polymerase chain reaction on a sample of oral mucosa cells obtained by buccal
      swabs. RESULTS: Odds ratio for melanoma was increased not significantly in case
      of fair hair/eye color, presence of many naevi or solar lentigines, or history of
      actinic keratosis, skin cancer or sunburns; frequencies of GSTM1 null, GSTT1 null
      and all their possible combinations were not significantly different between
      patients and controls. CONCLUSIONS: Our results, in agreement with worldwide
      literature, show that melanoma is apparently independent from genetic lack of
      GSTM1/GSTT1. However, melanoma is notoriously linked to a history of sunburns,
      and GSTM1/GSTT1 null are a significant risk factor for sunburns. We describe a
      possible explanation of this apparent contradiction, taking into account the
      different roles of the multiple components of human skin in photoprotection, and
      their variable importance in different conditions of exposure to UV radiations.
      Simultaneous evaluation of a larger number of components of the antioxidant
      system, to assess their individual contribution to protection against melanoma,
      is advisable and should be considered in future studies. This could allow to
      better define risks for each patient and possibly to tailor preventive measures.

PMID- 25588059
TI  - TRF2: TRansForming the view of general transcription factors.
AB  - Transcriptional regulation is pivotal for development and differentiation of
      organisms. Transcription of eukaryotic protein-coding genes by RNA polymerase II
      (Pol II) initiates at the core promoter. Core promoters, which encompass the
      transcription start site, may contain functional core promoter elements, such as
      the TATA box, initiator, TCT and downstream core promoter element. TRF2 (TATA-box
      binding protein-related factor 2) does not bind TATA box-containing promoters.
      Rather, it is recruited to core promoters via sequences other than the TATA box.
      We review the recent findings implicating TRF2 as a basal transcription factor in
      the regulation of diverse biological processes and specialized transcriptional
      programs. 

PMID- 25588062
TI  - Graphene/phase change material nanocomposites: light-driven, reversible
      electrical resistivity regulation via form-stable phase transitions.
AB  - Innovative photoresponsive materials are needed to address the complexity of
      optical control systems. Here, we report a new type of photoresponsive
      nanomaterial composed of graphene and a form-stable phase change material (PCM)
      that exhibited a 3 orders of magnitude change in electrical resistivity upon
      light illumination while retaining its overall original solid form at the
      macroscopic level. This dramatic change in electrical resistivity also occurred
      reversibly through the on/off control of light illumination. This was attributed
      to the reversible phase transition (i.e., melting/recrystallization) behavior of
      the microscopic crystalline domains present in the form-stable PCM. The
      reversible phase transition observed in the graphene/PCM nanocomposite was
      induced by a reversible temperature change through the on/off control of light
      illumination because graphene can effectively absorb light energy and convert it
      to thermal energy. In addition, this graphene/PCM nanocomposite also possessed
      excellent mechanical properties. Such photoresponsive materials have many
      potential applications, including flexible electronics. 

PMID- 25588061
TI  - Tuscan consensus on the diagnosis, treatment and follow-up of moderate-to-severe
      psoriasis.
AB  - BACKGROUND: Psoriasis is traditionally defined as an inflammatory chronic
      relapsing disease of the skin. As widely demonstrated, this disease is also
      associated with multiple comorbidities: arthropathy, inflammatory bowel disease,
      metabolic, cardiovascular, ocular and psychological disorders. The disease also
      has a significant impact on patients' quality of life, whose work ability
      decreases considerably with clear consequences for the social costs. Therefore,
      if we consider that in Tuscany, more than 100,000 people out of 3,672,202 suffer
      from psoriasis, it is of paramount importance focusing the attention on a
      rational model of clinical and therapeutic management of the disease. All the
      leading experts in Tuscany have come together with the aim of defining
      unanimously accepted regional guidelines for the diagnosis, treatment, follow-up
      and management of psoriasis, and of providing practical guidance/protocol on
      diagnosis, treatment, follow-up and management of special cases of moderate-to
      severe plaque psoriasis. METHODS: In a working group formed ad hoc, the main
      topics have been discussed and approved by plenary vote. RESULTS: Diagnosis must
      include a proper general health condition overview, a careful evaluation of skin
      and joints, the assessment and management of other comorbidities and the
      definition of disease severity. With regards to the therapy the best time to
      start a systemic treatment, the therapeutic goal, the most appropriate drug and
      blood tests to be performed in case of moderate severe-psoriasis have been taken
      into account. During follow-up, proper monitoring of systemic therapy and its
      management in the long term has also been suggested. Eventually, the experts have
      addressed the problem of how to manage the disease in special conditions, such as
      during surgery, pregnancy, in children and in case of infections (HBV, HCV, HIV).
      CONCLUSIONS: The main aim of this Consensus was to find agreement on the criteria
      for diagnosis, treatment and follow-up of psoriasis, shared by all the
      Dermatologic Therapy Units of Tuscany. A need to create an easier way for the
      patient to access specialized dermatology outpatient services, and to reduce the
      waiting list and costs related to the management of psoriasis has been stressed.
      Most importantly, during the Consensus all of the participants agreed on the
      central role of the patient, and on the need of a multidisciplinary management of
      the disease which requires communication among specialists and regional centers
      in order to build on existing experience.

PMID- 25588063
TI  - Poly(vinyl ester 1,2,3-triazolium)s: a new member of the poly(ionic liquid)s
      family.
AB  - A vinyl ester monomer carrying a pendant 1,2,3-triazole group is synthesized in
      two steps and polymerized by cobalt-mediated radical polymerization. Subsequent
      alkylation with N-methyl bis[(trifluoromethyl)sulfonyl]imide affords the
      corresponding poly(vinyl ester 1,2,3-triazolium). This unprecedented example of
      poly(vinyl ester ionic liquid) exhibits an ionic conductivity of 9.2 * 10(-7) S
      cm(-1) at 30  degrees C. 

PMID- 25588064
TI  - Manipulations to the Alcohol and Sodium Content of Beer for Postexercise
      Rehydration.
AB  - The addition of 25 mmol.L(-1) sodium to low alcohol (2.3% ABV) beer has been
      shown to enhance post exercise fluid retention compared with full strength (4.8%
      ABV) beer with and without electrolyte modification. This investigation explored
      the effect of further manipulations to the alcohol and sodium content of beer on
      fluid restoration following exercise. Twelve male volunteers lost 2.03 +/- 0.19%
      body mass (mean +/- SD) using cycling-based exercise. Participants were then
      randomly allocated a different beer to consume on four separate occasions. Drinks
      included low alcohol beer with 25 mmol.L-1 of added sodium [LightBeer+25], low
      alcohol beer with 50 mmol.L(-1) of added sodium [LightBeer+50], midstrength beer
      (3.5% ABV) [Mid] or midstrength beer with 25 mmol.L(-1) of added sodium [Mid+25].
      Total drink volumes in each trial were equivalent to 150% of body mass loss
      during exercise, consumed over a 1h period. Body mass, urine samples and
      regulatory hormones were obtained before and 4 hr after beverage consumption.
      Total urine output was significantly lower in the LightBeer+50 trial (1450 +/-
      183 ml) compared with the LightBeer+25 (1796 +/- 284 ml), Mid+25 (1786 +/- 373
      ml) and Mid (1986 +/- 304 ml) trials (all p < .05). This resulted in
      significantly higher net body mass following the LightBeer+50 trial (-0.97 +/-
      0.17 kg) compared with all other beverages (LightBeer+25 (-1.30 +/- 0.24 kg),
      Mid+25 (-1.38 +/-0.33 kg) and Mid (-1.58 +/-0.29 kg), all p < .05). No
      significant changes to aldosterone or vasopressin were associated with different
      drink treatments. The electrolyte concentration of low alcohol beer appears to
      have more significant impact on post exercise fluid retention than small changes
      in alcohol content.

PMID- 25588065
TI  - Assessing implicit mate preferences among Chinese and Japanese women by providing
      love, sex, or money cues.
AB  - Love, sex, and money are the most direct cues involved in the fundamental forms
      of mate preferences. These fundamental forms are not mutually exclusive but are
      interrelated. As a result, humans base their mate choices on multiple cues. In
      this study, 62 undergraduate women (M age = 20.4 yr., SD = 1.4) from China and
      Japan served as the participants. They performed a variation of the semantic
      priming task, in which they were instructed to decide by means of a key-press
      whether the target was human or non-human. The primes were images that portrayed
      potent evolutionary factors for mate preference (i.e., love, sex, and money), and
      the manipulation was based on whether the prime and target matched regarding
      gender, independent of the target decision task (human vs non-human).
      Participants gave faster responses to male targets than to female targets under
      priming. The results generally supported the evolutionary premises that assume
      mate preference is determined by fundamental forms of providing emotional (love),
      material (money), and fertility support (sex). The money priming effect was
      stronger in the Chinese women than in the Japanese women, suggesting that social
      context may influence mate preferences.

PMID- 25588066
TI  - Resource-independent negative effects of foreign language on analogical problem
      solving.
AB  - It has been shown that analogical problem solving is more difficult when a target
      problem is written in a foreign language than in one's native language. Possible
      resource-independence of this negative effect of a foreign language was
      investigated. After reading an analog or a filler story, participants solved a
      target problem written in their native or a foreign language. Those who read the
      problem in their native language performed a concurrent task to reduce their
      available processing resources. Nevertheless, they were better able to solve it
      than those who read the problem in a foreign language after reading the analog.
      This indicates that reading the problem in a foreign language decreases
      analogical problem-solving ability in a resource-independent manner.

PMID- 25588067
TI  - Effects of temporary intensive feed restriction on performance, nutrient
      digestibility and carcass criteria of growing male Californian rabbits.
AB  - The aim of the study was to evaluate the effect of a temporary quantitative feed
      restriction on growth performance, nutrient digestibility and carcass criteria of
      rabbits. A total of 80 weaned male Californian rabbits (30 d of age) were
      randomly assigned to four treatments of 20 rabbits each. The Control group was
      fed ad libitum during the whole experimental period (days 30-72 of age). For the
      three restricted fed groups the feed intake was reduced by 15%, 30% and 45%
      compared to the Control group, respectively. The feed restriction was applied
      after weaning and lasted for 21 d. Thereafter, at 51 d of age, in all treatments
      the feed supply returned to ad libitum intake till 72 d of age (AL period). The
      feed restriction decreased the body weight gain of rabbits (during the
      restriction period and the whole experimental period, p < 0.001) and improved
      feed conversion ratio during all tested periods (p < 0.001). In the AL period,
      the daily body weight gain of all groups was similar. After the AL period, the
      digestibility of all measured nutrients was significantly higher for animals fed
      restrictively. Furthermore, feed restrictions significantly decreased the
      proportion of perirenal and scapular fat and increased relative weight and length
      of the gastrointestinal tract. Therefore, it can be concluded that the applied
      feed restriction improved feed conversion, nutrient digestibility and reduced fat
      at the slaughter age of Californian rabbits, but the reduced body weight gain
      could not be compensated by a subsequent ad libitum feeding for 3 weeks.

PMID- 25588068
TI  - Different VanA Elements in E. faecalis and in E. faecium Suggest at Least Two
      Origins of Tn1546 Among VRE in a Brazilian Hospital.
AB  - In 2009 during surveillance in a Brazilian hospital, many patients were confirmed
      to be colonized by vancomycin-resistant enterococci (VRE) and a few infection
      cases occurred. Among 14 isolates of Enterococcus faecalis, most had the same
      pulsotype, virulence profile (agg(+)elrA(+)gelE(+)), and were sequence type
      (ST)103, indicating dissemination of a clone. The 47 Enterococcus faecium were
      separated into four pulsotypes, the predominant virulence profile being
      esp(+)acm(+). All of them harbored the hospital marker IS16, and three randomly
      chosen isolates were ST412, belonging to the Clonal Complex 17. E. faecalis were
      all susceptible to penicillin and ampicillin, while all E. faecium were resistant
      to them. All isolates were susceptible to daptomycin and tigecycline. There were
      no rep-family genes common to all VRE. The VanA element of all E. faecium lost
      its left-side inverted repeat (IRL) region and had a specific IS insertion. On
      the other hand, all E. faecalis presented intact Tn1546. The size of plasmids
      containing the vanA gene as well as its rep-families varied between and within
      species. The lack of a vanA plasmid common to all VRE, together with the
      differences among VanA elements, despite the fact that some patients were
      colonized by both species during their hospitalization, leads us to suggest at
      least two different Tn1546 origins. 

PMID- 25588069
TI  - Individualizing oral busulfan dose after using a test dose in patients undergoing
      hematopoietic stem cell transplantation: pharmacokinetic characterization.
AB  - BACKGROUND: Busulfan is an alkylating agent used for conditioning patients
      undergoing hematopoietic stem cell transplantation with a narrow therapeutic
      range and highly variable pharmacokinetics. High concentrations induce toxicity,
      especially hepatic veno-occlusive disease, also referred to as sinusoidal
      obstruction syndrome. This study aimed to assess busulfan pharmacokinetic
      variability in pretransplant conditioning regimens using an analytical method
      validated by high-performance liquid chromatography coupled to diode array
      detector (HPLC/PDA). METHODS: Eight patients who used the test dose (TD) of 1
      mg/kg busulfan 10 days before conditioning were included, and 10 serial blood
      samples were collected to determine: the elimination half-life (t1/2), total area
      under the curve (AUCT), total clearance (Cl(T)/F), and plasma concentration at
      steady state (C(ss)), using a monocompartmental model and first-order kinetics.
      The instrumental conditions were: HPLC/PDA Shimadzu, column ACE C18 (150 mm * 4
      mm); methanol/water/acetonitrile (65:20:15) eluent flow rate of 1 mL/min; 1,6-bis
      (methanesulfonyloxy)-hexane; UV lambda = 276 nm; analysis time 17 minutes; and
      derivatization with sodium diethylcarbamate. The dose was adjusted, and 4 blood
      samples per day were collected at days 2, 3, and 4 of treatment for new plasma
      determinations. RESULTS: Four patients needed higher doses; the mean dose
      administered was 1.02 +/- 0.19 mg/kg. Mean results at TD: t1/2 = 2.88 +/- 0.5
      hours; Cl(T)/F = 0.18 +/- 0.03 L . h(-1) . kg(-1); AUC(T) = 5461.00 +/- 961.15 ng
      . mL(-1) . h(-1); and C(ss) = 911.3 +/- 159.8 ng/mL. Mean results of samples
      collected during conditioning: t1/2 = 3.21 +/- 0.9 hours; Cl(T)/F = 0.13 +/- 0.02
      L . h(-1) . kg(-1); AUC(T) = 7571 +/- 1705 ng . mL(-1) . h(-1); and C(ss) =
      1262.0 +/- 284.3 ng/mL. CONCLUSIONS: High variability in the assessed
      pharmacokinetic parameters was observed, with a 38% variation in C(ss) between TD
      and conditioning regimen; Cl(T)/F decreased by 30%, suggesting drug accumulation
      after multiple-dose regimen. Although being lower than reported in the
      literature, this variation may be associated with toxicity of the proposed
      treatment, justifying patient monitoring and enhancing validity of previous
      pharmacokinetic evaluation using TD regimen.

PMID- 25588072
TI  - A microporous metal-organic framework with rare lvt topology for highly selective
      C2H2/C2H4 separation at room temperature.
AB  - A new lvt-type metal-organic framework UTSA-60a with suitable pore channels and
      open metal sites has been developed for highly selective separation of C2H2/C2H4
      at room temperature. 

PMID- 25588070
TI  - Expert system for predicting reaction conditions: the Michael reaction case.
AB  - A generic chemical transformation may often be achieved under various synthetic
      conditions. However, for any specific reagents, only one or a few among the
      reported synthetic protocols may be successful. For example, Michael beta
      addition reactions may proceed under different choices of solvent (e.g.,
      hydrophobic, aprotic polar, protic) and catalyst (e.g., Bronsted acid, Lewis
      acid, Lewis base, etc.). Chemoinformatics methods could be efficiently used to
      establish a relationship between the reagent structures and the required reaction
      conditions, which would allow synthetic chemists to waste less time and resources
      in trying out various protocols in search for the appropriate one. In order to
      address this problem, a number of 2-classes classification models have been built
      on a set of 198 Michael reactions retrieved from literature. Trained models
      discriminate between processes that are compatible and respectively processes not
      feasible under a specific reaction condition option (feasible or not with a Lewis
      acid catalyst, feasible or not in hydrophobic solvent, etc.). Eight distinct
      models were built to decide the compatibility of a Michael addition process with
      each considered reaction condition option, while a ninth model was aimed to
      predict whether the assumed Michael addition is feasible at all. Different
      machine-learning methods (Support Vector Machine, Naive Bayes, and Random Forest)
      in combination with different types of descriptors (ISIDA fragments issued from
      Condensed Graphs of Reactions, MOLMAP, Electronic Effect Descriptors, and
      Chemistry Development Kit computed descriptors) have been used. Models have good
      predictive performance in 3-fold cross-validation done three times: balanced
      accuracy varies from 0.7 to 1. Developed models are available for the users at
      http://infochim.u-strasbg.fr/webserv/VSEngine.html . Eventually, these were
      challenged to predict feasibility conditions for ~50 novel Michael reactions from
      the eNovalys database (originally from patent literature). 

PMID- 25588073
TI  - Cross-dehydrogenative coupling of azoles with alpha-C(sp3)-H of ethers and
      thioethers under metal-free conditions: functionalization of H-N azoles via C-H
      activation.
AB  - A metal-free cross-dehydrogenative coupling method for the synthesis of N
      substituted azoles has been developed. The TBAI/TBHP system catalyzed the
      coupling of azoles with ethers and thioethers via alpha-C(sp(3))-H activation.
      Under the optimized conditions, a diverse range of un/substituted azoles such as
      1H-benzimidazole, 9H-purine, 1H-benzotriazole, 1H-1,2,3-triazole, 1H-1,2,4
      triazole, and 1H-pyrazole were successfully employed for coupling with various
      ethers and thioethers such as tetrahydrofuran, tetrahydropyran, 1,4-dioxane,
      diethyl ether, tetrahydrothiophene, and 1,3-dithiolane. 

PMID- 25588075
TI  - Validity of clinic blood pressure compared to ambulatory monitoring in
      hypertensive patients in a primary care setting.
AB  - AIMS: To determine the validity of the blood pressure (BP) measurement in a
      primary care setting in comparison with the measurement obtained from 24-h
      ambulatory blood pressure monitoring (ABPM). METHODS: Patients with hypertension
      (n = 137) were studied in primary care. Immediately after a nurse took two
      measurements of each patient's BP, the ABPM device was attached. Agreement was
      determined using the Bland-Altman method and the Kappa index. The sensitivity,
      specificity, predictive values and likelihood ratios were calculated for the
      manual BP measurement in comparison with ABPM for the purpose of diagnosing
      uncontrolled BP. RESULTS: The BP values from ABPM were lower than those obtained
      in the examination room. The difference between the clinic measurement and the
      ABPM was 18.07 +/- 14.6 mmHg (systolic blood pressure, SBP) and 6.3 +/- 9.2 mmHg
      (diastolic blood pressure, DBP). The agreement between the clinic measurement and
      24h-ABPM for the purpose of classifying control or uncontrolled BP was 64.2%
      (Kappa = 0.311). In the case of ABPM, the sensitivity of the measurement in the
      examination room for diagnosing uncontrolled BP was 80.36%, specificity was
      53.09%, positive predictive value 54.22% and negative predictive value 70.63%.
      CONCLUSIONS: Clinic measurements do not have sufficient sensitivity/specificity
      to be recommended as a single method of BP control in primary care.

PMID- 25588076
TI  - Criterion Validity and Practical Utility of the Minnesota Multiphasic Personality
      Inventory-2-Restructured Form (MMPI-2-RF) in Assessments of Police Officer
      Candidates.
AB  - Minnesota Multiphasic Personality Inventory-2-Restructured Form scores for 145
      male police officer candidates were compared with supervisor ratings of field
      performance and problem behaviors during their initial probationary period.
      Results indicated that the officers produced meaningfully lower and less variant
      substantive scale scores compared to the general population. After applying a
      statistical correction for range restriction, substantive scale scores from all
      domains assessed by the inventory demonstrated moderate to large correlations
      with performance criteria. The practical significance of these results was
      assessed with relative risk ratio analyses that examined the utility of specific
      cutoffs on scales demonstrating associations with performance criteria. 

PMID- 25588077
TI  - Does induction time of mild hypothermia influence the survival duration of septic
      rats?
AB  - The relationship between hypothermia induction time and survival duration
      following sepsis was studied on 31 male Sprague-Dawley rats (median weight 311 g,
      range 260-356 g). After anesthesia and when the target temperature was reached
      (normothermia: 38 degrees C or mild induced hypothermia: 34 degrees C), sepsis
      was induced by cecal ligation and perforation. Five experimental groups were
      used. In groups 1 and 2, temperature of septic rats was maintained throughout the
      experiment at 38 degrees C (seven rats) or 34 degrees C (six rats), respectively.
      In groups 3, 4, and 5, septic rats (six per group) were maintained at 38 degrees
      C for 1, 2, and 3 hours, respectively, and then placed in mild hypothermia (34
      degrees C). For each group, the survival duration was determined and blood
      samples were performed at the tail to measure tumor necrosis factor-alpha (TNF
      alpha) plasma concentration. Whatever the experimental group, a decrease in
      temperature from 38 degrees C to 34 degrees C significantly increased the
      survival duration of septic rats compared with those maintained at 38 degrees C
      throughout the experiment. The delay between the onset of sepsis and induction of
      hypothermia was also crucial. Thus, hypothermia induced after 1 hour of sepsis at
      38 degrees C significantly increased the survival duration of septic rats (12
      hours 37 minutes+/-1 hour 4 minutes; group 3) compared with hypothermia induced
      after 3 hours of sepsis (8 hours 56 minutes+/-1 h 20 minutes; group 5). Moreover,
      except for group 5, survival duration improvement of septic rats observed in
      hypothermia was related to a lower increase of TNF-alpha plasma concentration
      compared with septic rats in normothermia. During sepsis, mild induced
      hypothermia significantly increased the survival duration of septic rats. The
      earlier hypothermia was applied, the longer the septic rats survived. According
      to these results, hypothermia may therefore provide the necessary time to apply a
      proper treatment.

PMID- 25588078
TI  - An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA
      stability during mitogenic stimulation.
AB  - Mitogen-activated protein kinase (MAPK) pathways constitute key regulatory
      elements linking extracellular stimuli to nuclear gene expression. Immediate
      early responsive genes (IEGs) of the activator protein 1 (AP-1) family, such as
      fos, achieve peak expression levels shortly after cells are stimulated with
      growth factors and sharply decrease thereafter. Several AU-rich binding proteins
      (AUBPs), including HuR (Hu-antigen R, Elav-like protein 1, ELAVL1) and KSRP (far
      upstream element-binding protein 2, KHSRP) bind to a fos AU-rich element (ARE)
      present in the 3'-UTR (untranslated region) of fos mRNA regulating its stability
      by a still poorly defined mechanism. We show in the present study that, whereas
      HuR binds and stabilizes transcribed reporter mRNAs bearing the fos 3'-UTR, KSRP
      counteracts this effect. Furthermore, we found that fos mRNA stability and HuR
      phosphorylation status are dependent on the activity of p38 MAPK in both
      epithelial cells and fibroblasts upon proliferative stimulation. Analysing PPI
      (protein-protein interaction) networks, we performed a thorough query of
      interacting proteins for p38 MAPKs, HuR and other AUBPs upon growth factor
      stimulation. This revealed novel HuR interactors including inhibitors of protein
      phosphatase 2 (PP2A) activity. Over-expression of two of these interactors, pp32
      and APRIL (acidic leucine-rich nuclear phosphoprotein 32 family member B, ANP32B)
      and pharmacological inhibition of PP2A stabilized a fos reporter mRNA. Our
      results indicate that p38 MAPK regulates fos mRNA decay by affecting the state of
      phosphorylation of HuR while controlling yet to be fully elucidated PP regulatory
      networks. 

PMID- 25588080
TI  - Chemical composition of essential oils from the vegetative and reproductive
      structures of Copaifera langsdorffii Desf.
AB  - GC/FID and GC-MS analysis revealed germacrene D, bicyclogermacrene, alpha-cadinol
      and cubenol as major compounds from aril. Germacrene D, bicyclogermacrene, trans
      caryophyllene and delta-elemene are major compounds in fruits. Germacrene D,
      spathulenol, trans-caryophyllene and caryophyllene oxide are major compounds in
      leaves. Furthermore, multivariate analysis revealed distinct groups between the
      composition of essential oils from aril and fruit, when compared with terpene
      production found in leaves. Lipid composition found in arils could be protected
      by the presence of non-oxygenated sesquiterpenes, as germacrene D and
      bicyclogermacrene. Chemical profiles of essential oils from the fruits, arils and
      leaves of Copaifera langsdorffii Desf. revealed different compositions, which
      could be related to environmental pressures. Thereby, non-oxygenated
      sesquiterpenes can also work against herbivory, pathogens and predator's attack,
      emphasising the importance of further studies among terpenes, ecology
      interactions and plant physiology. 

PMID- 25588079
TI  - Timing of subsequent new tumors in patients who present with basal cell carcinoma
      or cutaneous squamous cell carcinoma.
AB  - IMPORTANCE: Patients with basal cell carcinoma (BCC) and cutaneous squamous cell
      carcinoma (SCC) (often termed nonmelanoma skin cancer or keratinocyte carcinoma
      [KC]) often develop new KCs, but information is limited on the frequency and
      timing of these subsequent tumors. This information is crucial to guide follow-up
      care. OBJECTIVE: To determine the timing of subsequent new KCs in patients who
      present with KC. DESIGN, SETTING, AND PARTICIPANTS: We enrolled a consecutive
      cohort of 1426 patients diagnosed as having biopsy-proven KC from January 1,
      1999, through December 31, 2000, in a university dermatology practice and its
      affiliated Department of Veterans Affairs dermatology service. After exclusion of
      patients with basal cell nevus syndrome and immunocompromise, 1284 patients
      (90.0%) were followed up prospectively for a mean of 5.7 (range, 0-12.3) years.
      MAIN OUTCOMES AND MEASURES: We assessed the risks for subsequent KCs over time
      using single-failure and multiple-failure models. We separately assessed outcomes
      after first lifetime KCs and after nonfirst lifetime KCs. We also performed
      secondary analyses of the risk for a subsequent BCC after a prior BCC diagnosis
      and the risk for a subsequent SCC after a prior SCC diagnosis. RESULTS: The risk
      for a subsequent KC was substantially lower after the first lifetime KC
      diagnosis: 14.5% (95% CI, 11.9%-17.7%) at 1 year, 31.1% (95% CI, 27.3%-35.3%) at
      3 years, and 40.7% (95% CI, 36.5%-45.2%) at 5 years, than after a nonfirst KC:
      43.9% (95% CI, 42.0%-45.9%) at 1 year, 71.1% (95% CI, 69.1%-73.0%) at 3 years,
      and 82.0% (95% CI, 80.2%-83.7%) at 5 years. Secondary analyses of the risks for a
      subsequent BCC after a prior BCC diagnosis and of a subsequent SCC after a prior
      SCC diagnosis yielded results consistent with the analyses for the pooled KC
      sample. CONCLUSIONS AND RELEVANCE: Although all patients with KC are assumed to
      be at high risk for subsequent tumors, a subset may not develop another KC after
      their first tumor. Whether these findings are related to biological or behavioral
      differences or to differences in health care services should be investigated
      further to inform and improve care. Ongoing routine screening for subsequent KC
      may not be indicated for all patients with KC. Skin cancer screening can be
      improved with a better understanding of the course and frequency of subsequent KC
      diagnoses.

PMID- 25588081
TI  - Older persons' perceptions of general practitioner or specialist primary care
      physicians: same point of view?
AB  - BACKGROUND: Identification of a Primary Care Physician (PCP) by older patients is
      considered as essential for the coordination of care, but the extent to which
      identified PCPs are general practitioners or specialists is unknown. This study
      described older patients' experiences with their PCP and tested the hypothesis of
      differences between patients who identify a specialist as their PCP (SP PCP) and
      those who turn to a general practitioner (GP PCP). METHODS: In 2012, a cross
      sectional postal survey on care was conducted in the 68+ year old population of
      the canton of Vaud. Data was provided by 2,276 participants in the ongoing
      Lausanne cohort 65+ (Lc65+), a study of those born between 1934 and 1943, and by
      998 persons from an additional sample drawn to include the population outside of
      Lausanne or born before 1934. RESULTS: Participants expressed favourable
      perceptions, at rates exceeding 75% for most items. However, only 38% to 51%
      responded positively for out-of-hours availability, easy access and at home
      visits, likelihood of prescribing expensive medication if needed, and doctors'
      awareness of over-the-counter drugs. 12.0% had an SP PCP, in 95.9% specialised in
      a discipline implying training in internal medicine. Bivariate and multivariate
      analyses did not result in significant differences between GP and SP PCPs
      regarding perceptions of accessibility/availability, doctor-patient relationship,
      information and continuity of care, prevention, spontaneous use of the emergency
      department or ambulatory care utilisation. CONCLUSIONS: Experiences of old
      patients were mostly positive despite some lack in reported hearing, memory
      testing, and colorectal cancer screening. We found no differences between GP and
      SP PCP groups.

PMID- 25588082
TI  - Serum endocan levels are correlated with the presence and severity of coronary
      artery disease in patients with hypertension.
AB  - BACKGROUND: Endothelial dysfunction is one of the most important early indicators
      of atherosclerosis in hypertension (HT) patients. Endocan has been reported to
      play a role in the pathophysiology of endothelial dysfunction. OBJECTIVE: We
      sought to assess whether serum endocan levels are correlated with the presence
      and severity of coronary artery disease (CAD) in patients with HT. METHODS: We
      measured endocan levels in 164 patients with HT and in 55 controls. The severity
      of CAD was assessed by the coronary atherosclerosis index scores. RESULTS: Serum
      endocan levels were independently correlated with the presence and severity of
      CAD in HT patients. CONCLUSION: Endocan might function as a useful biomarker for
      monitoring the development and progression of CAD in HT patients.

PMID- 25588083
TI  - Aflibercept: an update on recent milestones achieved.
AB  - In the last decade, intravitreal medications targeted to vascular endothelial
      growth factor (VEGF) such as pegaptanib, ranibizumab and bevacizumab have
      revolutionized the treatment and significantly improved visual acuity outcomes in
      patients with retinal vascular diseases such as age-related macular degeneration
      (AMD), diabetic macula edema (DME) and retinal vein occlusion (RVO). In recent
      years, aflibercept, an anti-VEGF drug that targets all isoforms of VEGF as well
      as placenta growth factor, has shown similar effectiveness in recent clinical
      trials. Aflibercept has firmly joined ranibizumab and bevacizu-mab as an
      important therapeutic option in the management of neovascular AMD. More recently,
      aflibercept appears to be contending with ranibizumab and bevacizumab as an
      important therapeutic option in the management of DME and RVO. 

PMID- 25588084
TI  - Nivolumab.
AB  - Until recently, a treatment for advanced melanoma with a tolerable side effect
      profile has remained elusive. Therefore, despite its relatively rare occurrence,
      melanoma continues to cause the majority of skin cancer deaths, with less than
      15% of those affected with late-stage disease surviving 10 years or more.
      Historically, the mainstay of treatment has been single-agent chemotherapy or
      immunotherapy with the alkylating agent dacarbazine and interleukin-2 or
      interferon. Cytotoxic chemotherapy with dacarbazine demonstrated poor response
      rates and little or no survival benefit, whereas IL-2 and interferon, although
      showing durable responses, are associated with poor side effect profiles (1, 2).
      However, with the elucidation of the molecular biology and oncogenic pathways
      involved in melanoma, agents targeted against mutations in the mitogen-activated
      protein kinase (MAPK) pathway including BRAF and MEK inhibitors have demonstrated
      prolonged survival and more manageable side effect profiles relative to
      traditional chemotherapy. Simultaneously, an evolved understanding of the
      immunologic basis for the development and regression of melanoma lead to the
      discovery of immune checkpoint inhibitors, which confer a similar survival
      benefit. Foremost among these was ipilimumab, a monoclonal antibody against the
      negative regulatory checkpoint molecule cytotoxic T-lymphocyte protein 4 (CTLA
      4), which was the first drug in the management of metastatic melanoma to confer a
      survival benefit. However, treatment is complicated by a high rate of grade 3 and
      4 immune-related adverse events and limited response. Nivolumab, a fully human
      monoclonal antibody against programmed cell death protein 1 (PD-1), has shown a
      survival benefit in an open-label phase II trial, and was the first PD-1
      inhibitor to be approved worldwide. With a favorable side effect profile and
      ongoing trials in combination with extant therapies, nivolumab shows substantial
      potential to further augment the options for an effective treatment in malignant
      melanoma. 

PMID- 25588085
TI  - Tamsulosin/solifenacin fixed-dose combination tablet for the treatment of male
      lower urinary tract symptoms.
AB  - Men reporting mixed storage and voiding lower urinary tract symptoms (LUTS) often
      experience persisting storage LUTS after initial treatment. Combination therapy
      of an alpha-adrenergic antagonist and an antimuscarinic is increasingly
      recognized as a therapy option. Clinical trials have combined tamsulosin (0.4 mg)
      with different doses of solifenacin. In the SATURN study, greater efficacy
      benefits were observed for moderate to severe storage symptoms. Single tablet
      administration may offer improved compliance. Accordingly, the NEPTUNE study
      researched fixed-dose combination (FDC) therapy for mixed LUTS, using tamsulosin
      (oral controlled administration system formulation), with solifenacin (6 or 9
      mg). The FDC containing tamsulosin and solifenacin 6 mg improved storage and
      voiding LUTS, with no additional benefit from the higher solifenacin dose. During
      the open-label extension study, symptom improvement was maintained. Adverse
      events reflected the known effects of the component therapies. Acute urinary
      retention, an adverse event of special interest, was seen in only a small number
      of treated men. 

PMID- 25588086
TI  - Technosphere inhaled insulin (Afrezza).
AB  - Technosphere(r) insulin uses a unique carrier -fumaryl diketopiperazine (FDKP)-
      which adsorbs insulin to form microparticles to permit delivery to the alveoli by
      inhalation. Toxicity studies have been entirely negative. The pulmonary
      absorption of insulin is very rapid, and the disappearance time is shorter than
      for subcutaneously delivered rapid-acting insulins. As a result, after
      inhalation, there is a rapid drop in glucose levels which subsequently return to
      normal in a shorter time than after subcutaneous insulin administration.
      Consequently, there is a lower incidence of hypoglycemic reactions. Pulmonary
      function studies have shown a small, reversible decrease in FEV1, and pulmonary
      imaging studies have shown no adverse effect. The inhalation of Technosphere
      insulin can produce a cough in up to 27% of patients. The cough has resulted in
      discontinuance in as many as 9% of users. Technosphere insulin has been approved
      for use in type 1 and type 2 diabetes. Long-term studies of pulmonary safety and
      surveillance for malignancy will be performed in the future. Studies to assess
      the optimal time dosing regimen are needed. 

PMID- 25588087
TI  - A report from the 2014 American College of Rheumatology/Association of
      Rheumatology Health Professionals Annual Meeting (November 14-19 - Boston,
      Massachusetts, USA).
AB  - With freezing cold temperatures outside but great excitement for new research
      inside Boston's Convention and Exhibition Center, clinical research on recently
      launched and investigational small molecular drugs and biologics as well as
      preclinical research with novel compounds acting on new targets that are paving
      the way to future developments in the therapeutic armamentarium against
      rheumatoid arthritis and other bone and joint diseases focused the attention of
      researchers and clinicians attending this year's scientific sessions of the
      American College of Rheumatology. The conference started with a full-blast poster
      session during which significant research advancements were disclosed, but
      parallel abstract sessions were not far behind in attendance, hooking the
      interest of attendees from across the world. 

PMID- 25588088
TI  - CE: Original research: hospital system barriers to rapid response team
      activation: a cognitive work analysis.
AB  - BACKGROUND: The goal of rapid response team (RRT) activation in acute care
      facilities is to decrease mortality from preventable complications, but such
      efforts have been only moderately successful. Although recent research has shown
      decreased mortality when RRTs are activated more often, many hospitals have low
      activation rates. This has been linked to various hospital, team, and nursing
      factors. Yet there is a dearth of research examining how hospital systems shape
      nurses' behavior with regard to RRT activation. Making systemic constraints
      visible and modifying them may be the key to improving RRT activation rates and
      saving more lives. PURPOSE: The purpose of this study was to use cognitive work
      analysis to describe factors within the hospital system that shape medical
      surgical nurses' RRT activation behavior. METHODS: Cognitive work analysis offers
      a framework for the study of complex sociotechnical systems. This framework was
      used as the organizing element of the study. Qualitative descriptive design was
      used to obtain data to fill the framework's five domains: resources, tasks,
      strategies, social systems, and worker competency. Data were obtained from
      interviews with 12 medical-surgical nurses and document review. Directed content
      analysis was used to place the obtained data into the framework's predefined
      domains. RESULTS: Many system factors affected participants' decisions to
      activate or not activate an RRT. Systemic constraints, especially in cases of
      subtle or gradual clinical changes, included a lack of adequate information, the
      availability of multiple strategies, the need to justify RRT activation, a
      scarcity of human resources, and informal hierarchical norms in the hospital
      culture. The most profound constraint was the need to justify the call.
      Justification was based on the objective or subjective nature of clinical
      changes, whether the nurse expected to be able to "handle" these changes, the
      presence or absence of a physician, and whether there was an expectation of
      support from the RRT team. The need for justification led to delays in RRT
      activation. CONCLUSIONS: Although it's generally thought that RRTs are activated
      without hesitation, this study found the opposite was true. All of the
      aforementioned constraints increase the cognitive processing load on the nurse.
      The value of the RRT could be increased by modifying these constraints-in
      particular, by lifting the need to justify calls, improving protocols, and
      broadening the range of culturally acceptable triggers-and by involving the RRT
      earlier in patient cases through discussion, consultation, and collaboration.

PMID- 25588089
TI  - CE: Long-term outcomes after repair of congenital heart defects: part 2.
AB  - OVERVIEW: Many congenital heart defects can be repaired, but long-term monitoring
      is often required to forestall possible complications. This two-part article
      reviews 10 common congenital heart defects, their repairs, and their common long
      term outcomes, along with the implications for nurses in cardiac and noncardiac
      settings alike. Here, in part 2, the author reviews four defects: tetralogy of
      Fallot, transposition of the great arteries, congenitally corrected transposition
      of the great arteries, and single-ventricle defects.

PMID- 25588090
TI  - A bold new vision for America's health care system.

PMID- 25588092
TI  - Atom-economical transformation of diaryliodonium salts: tandem C-H and N-H
      arylation of indoles.
AB  - Arylation using diaryliodonium salts generates one equivalent of an iodoarene as
      a side-product, a significant waste of atom economy. Here, we show that
      diaryliodoniums can undergo Cu-catalyzed tandem C-H/N-H arylation, producing
      novel indoles that incorporate both aryl groups from the reagent. 

PMID- 25588091
TI  - Muscle atrophy and metal-on-metal hip implants: a serial MRI study of 74 hips.
AB  - BACKGROUND AND PURPOSE: Muscle atrophy is seen in patients with metal-on-metal
      (MOM) hip implants, probably because of inflammatory destruction of the musculo
      tendon junction. However, like pseudotumors, it is unclear when atrophy occurs
      and whether it progresses with time. Our objective was to determine whether
      muscle atrophy associated with MOM hip implants progresses with time. PATIENTS
      AND METHODS: We retrospectively reviewed 74 hips in 56 patients (32 of them
      women) using serial MRI. Median age was 59 (23-83) years. The median time post
      implantation was 83 (35-142) months, and the median interval between scans was 11
      months. Hip muscles were scored using the Pfirrmann system. The mean scores for
      muscle atrophy were compared between the first and second MRI scans. Blood cobalt
      and chromium concentrations were determined. RESULTS: The median blood cobalt was
      6.84 (0.24-90) ppb and median chromium level was 4.42 (0.20-45) ppb. The median
      Oxford hip score was 34 (5-48). The change in the gluteus minimus mean atrophy
      score between first and second MRI was 0.12 (p = 0.002). Mean change in the
      gluteus medius posterior portion (unaffected by surgical approach) was 0.08 (p =
      0.01) and mean change in the inferior portion was 0.10 (p = 0.05). Mean
      pseudotumor grade increased by 0.18 (p = 0.02). INTERPRETATION: Worsening muscle
      atrophy and worsening pseudotumor grade occur over a 1-year period in a
      substantial proportion of patients with MOM hip implants. Serial MRI helps to
      identify those patients who are at risk of developing worsening soft-tissue
      pathology. These patients should be considered for revision surgery before
      irreversible muscle destruction occurs.

PMID- 25588093
TI  - Why do patients keep coming back? Results of a readmitted patient survey.
AB  - Hospital readmissions can negatively impact cost and patient outcomes. Predictors
      of 30-day readmissions have been primarily identified using medical claims data.
      Reported here are results of a patient survey developed as part of regular
      hospital quality assurance activities. Two-thirds of patients reported good
      discharge experiences but were still readmitted. One-third of patients discharged
      had a post-discharge doctor appointment scheduled; half were readmitted before
      that scheduled appointment. Results suggest post-discharge experiences could be
      improved, especially the timing of follow up doctor appointments. Identified
      weaknesses in the survey process highlight need for engagement of survey
      methodologists in efforts to understand patient experiences. 

PMID- 25588094
TI  - First childbirth and motherhood at post natural fertile age: a persistent and
      intergenerational experience of personal and social anomaly?
AB  - This study was aimed at understanding long-term psychosocial implications of
      first childbirth at post natural fertile age following assisted reproductive
      treatment. Twenty women, whose average age at childbirth was 45, participated.
      Findings show that the sense of anomaly experienced prior to pregnancy and
      childbirth related to infertility and advanced age continued during treatment,
      pregnancy, and motherhood. Participants associated their advanced age as cause
      for what they perceived as a similar sense of anomaly experienced by their
      children. The issue of a continuing and intergenerational sense of anomaly should
      be addressed when counseling women considering fertility treatment at advanced
      age. 

PMID- 25588095
TI  - Medication adherence skills training for African-American breast cancer
      survivors: the effects on health literacy, medication adherence, and self
      efficacy.
AB  - There are gaps in research regarding medication adherence, self-efficacy in
      proper medication adherence, and health literacy among breast cancer survivors.
      This pilot randomized controlled study was conducted to provide information
      addressing health literacy with respect to medication adherence and self-efficacy
      in African American breast cancer survivors. The study sample consisted of an
      intervention group (n = 24) of medication adherence skills training (MST) and a
      control group (n = 24), with a total sample population of 48 participants. The
      MST workshop was a collaborative intervention between pharmacy and social work
      and was designed to address issues that may be encountered while taking multiple
      medications for various acute and chronic conditions, increase participant
      confidence in accessing necessary resources for improved medication usage, and
      enhance personal self-efficacy regarding health care. A statistically significant
      relationship was detected between initial health literacy and medication
      adherence, as well as initial health literacy and self-efficacy. These findings
      indicated that individuals with higher health literacy were more likely to have
      higher levels of self-efficacy and were more likely to adhere to medication
      instructions. Analysis of the intervention and treatment groups did not show a
      statistically significant effect on health literacy, medication adherence, or
      self-efficacy from pre-test to post-test. 

PMID- 25588096
TI  - Barriers to cancer care, perceived social support, and patient navigation
      services for Korean breast cancer patients.
AB  - The present study aimed to examine the relationships among barriers to cancer
      care, perceived social support, and patient navigation services (PNS) for Korean
      breast cancer patients. For Korean breast cancer patients, PNS are comprised of
      five services, including emotional, financial, information, transportation, and
      disease management. The study findings demonstrated that transportation and
      disease management barriers were directly associated with PNS, whereas emotional
      and financial barriers were indirectly associated with PNS through perceived
      social support. The current study provides a preliminary Korean patient
      navigation model to identify how barriers to cancer care can be reduced through
      social support and PNS. 

PMID- 25588098
TI  - Resilience, self-efficacy, coping styles and depressive and anxiety symptoms in
      those newly diagnosed with multiple sclerosis.
AB  - High levels of depressive and anxiety symptoms have been reported by individuals
      with multiple sclerosis (MS). This study examined the associations between
      resilience, self-efficacy and coping and depressive and anxiety symptoms and
      whether resilience, self-efficacy and coping were predictors of depressive and
      anxiety symptoms in patients newly diagnosed with MS. A sample of 129 individuals
      newly diagnosed with MS participated in this cross-sectional study and completed
      an online questionnaire assessing resilience, self-efficacy, coping and
      depressive and anxiety symptoms. Results revealed that depressive and anxiety
      symptoms were significantly associated with problem-focused, emotion-focused and
      avoidance coping strategies, resilience and self-efficacy. Anxiety symptoms were
      also significantly associated with employment status and level of disability.
      Results from hierarchical multiple regression revealed that the resilience
      subscale of personal competence, the avoidance coping style of substance use and
      emotion-focused coping styles of venting predicted depressive symptoms and
      uniquely accounted for 63.8% of the variance in the depression score, F (18, 124)
      = 10.36, p = .000. Level of disability and employment status accounted for 13.2%
      of the anxiety score and avoidance coping style of denial and emotion-focused
      coping style of humour accounted for 36.4% of the variance in the anxiety symptom
      score, F (15, 112) = 6.37, p = .000. Our findings suggest that resilience and
      avoidance and emotion-focused coping strategies are predictive of depressive
      symptoms and anxiety symptoms in those newly diagnosed with MS. Resilience and
      coping styles may be another target for interventions aimed at managing
      depressive and anxiety symptoms in those newly diagnosed with MS. 

PMID- 25588097
TI  - Low health literacy and older adults: meanings, problems, and recommendations for
      social work.
AB  - Many older adults struggle to manage their health care problems. Low health
      literacy exacerbates such struggles and contributes to a variety of adverse
      health behaviors and outcomes. Addressing how health literacy impinges on the
      lives of older adults is a neglected area of social work practice and knowledge.
      This article explores seven areas: defining health literacy, the problem and
      prevalence of low health literacy among older adults, health inequalities and
      health literacy, a brief literature review, neglected issues in the literature,
      suggestions for macro and micro social work interventions to improve health
      literacy for older adult populations, and conclusion. 

PMID- 25588100
TI  - Photophysical Properties and Electronic Structure of Chlorin-Imides: Bridging the
      Gap between Chlorins and Bacteriochlorins.
AB  - Efficient light harvesting for molecular-based solar-conversion systems requires
      absorbers that span the photon-rich red and near-infrared (NIR) regions of the
      solar spectrum. Reported herein are the photophysical properties of a set of six
      chlorin-imides and nine synthetic chlorin analogues that extend the absorption
      deeper (624-714 nm) into these key spectral regions. These absorbers help bridge
      the gap between typical chlorins and bacteriochlorins. The new compounds have
      high fluorescence quantum yields (0.15-0.34) and long singlet excited-state
      lifetimes (4.2-10.9 ns). The bathochromic shift in Qy absorption is driven by
      substituent-based stabilization of the lowest unoccupied molecular orbital, with
      the largest shifts for chlorins that bear an electron-withdrawing, conjugative
      group at the 3-position in combination with a 13,15-imide ring. 

PMID- 25588101
TI  - Bright, efficient, and color-stable violet ZnSe-based quantum dot light-emitting
      diodes.
AB  - In this paper, highly stable violet-blue emitting ZnSe/ZnS core/shell QDs have
      been synthesized by a novel "low temperature injection and high temperature
      growth" method. The resulting nearly monodisperse ZnSe/ZnS core/shell QDs exhibit
      excellent characteristics such as a high color saturation (typical spectral full
      width at half-maximum between 12 and 20 nm), good emission tunability in the
      violet-blue range of wavelengths from 400 to 455 nm, a high absolute PL quantum
      yield (up to 83%), and superior chemical and photochemical stability. By
      employing ZnSe/ZnS core/shell quantum dots (QDs) as emitters with a fully
      solution processable method, bright, efficient, and color-stable violet Cd-free
      quantum dot-based light-emitting diodes (QD-LEDs) with maximum luminance up to
      2632 cd m(-2) and a peak EQE of 7.83% have been demonstrated successfully.
      Considering the factors of the photopic luminosity function, the brightness and
      efficiency results of such violet QD-LEDs not only represent a 12-fold increase
      in device efficiency and an extraordinary 100 times increase in luminance
      compared with previous Cd-free QD-LEDs but also can be much superior to the best
      performance (1.7%) of their Cd-based violet counterparts. These results
      demonstrate significant progress in short-wavelength QD-LEDs and shed light on
      the acceleration of commercial application of environmentally-friendly violet QD
      based displays and lighting. 

PMID- 25588099
TI  - Functional chromatographic technique for natural product isolation.
AB  - Natural product discovery arises through a unique interplay between
      chromatographic purification and biological assays. Currently, most techniques
      used for natural product purification deliver leads without a defined biological
      action. We now describe a technique, referred to herein as functional
      chromatography, that deploys biological affinity as the matrix for compound
      isolation. 

PMID- 25588102
TI  - Rapid quantification of digitoxin and its metabolites using differential ion
      mobility spectrometry-tandem mass spectrometry.
AB  - This study focuses on the quantitative analysis of the cardiac glycoside drug
      digitoxin and its three main metabolites digitoxigenin-bisdigitoxose,
      digitoxigenin-monodigitoxose, and digitoxigenin using electrospray ionization
      differential ion mobility spectrometry-tandem mass spectrometry (ESI-DMS-MS/MS).
      Despite large molecular weight differences, gas-phase separation of the four
      compounds in the DMS drift cell was not possible, even by utilizing additional
      volatile chemical modifiers. Baseline separation was achieved after adduct
      formation with alkali metal ions, however, and efficiency was shown to improve
      with increasing size of the alkali ion, reaching optimum conditions for the
      largest cesium ion. Subsequently, an assay was developed for quantification of
      digitoxin and its metabolites from human serum samples and its analytical
      performance assessed in a series of proof-of-concept experiments. The method was
      applied to spiked human serum pools with concentration levels between 2 and 80
      ng/mL. After a short reversed-phase chromatographic step for desalting the
      sample, rapid DMS separation of the analytes was carried out, resulting in a
      total run time of less than 1.5 min. The instrumental method showed good
      repeatability; the calculated coefficients of variation ranged from 2% to 13%. 

PMID- 25588103
TI  - Photoprotective effects of oxyresveratrol and Kuwanon O on DNA damage induced by
      UVA in human epidermal keratinocytes.
AB  - Ultraviolet A not only plays a major part in photoaging and skin tanning but also
      induces genetic damage and mutation in the epidermal basal layer of human skin.
      The photoprotective effect of oxyresveratrol and kuwanon O, two phenolic
      compounds from the root extract of Morus australis, in human primary epidermal
      keratinocytes was investigated in this study. Both of them were nontoxic to cells
      at a concentration less than 10 and 0.5 MUM, respectively. After pretreatment at
      the concentrations of 5 and 10 MUM, oxyresveratrol increased cell viability,
      exhibited significant suppressions on UVA- or H2O2-induced cellular ROS. UVA
      enhanced nitrotyrosine was also reduced by post-treatment with oxyresveratrol at
      theses concentrations. Kuwanon O presented similar inhibitions on cellular ROS
      and nitrotyrosine with lower concentrations (0.25 and 0.5 MUM), but there is no
      significant protection on cell survival after UVA irradiation. Their
      photoprotective effects also involved the enhanced repair of 8-hydroxy-2'
      deoxyguanosine (8-OHdG) and cyclobutane pyrimidine dimers (CPDs) as mediated by
      the augment of p53 expression after UVA radiation. 

PMID- 25588104
TI  - Fatty Acids Induce a Pro-Inflammatory Gene Expression Profile in Huh-7 Cells That
      Attenuates the Anti-HCV Action of Interferon.
AB  - The pathogenesis of nonalcoholic steatohepatitis is primarily an immune-driven
      disease and a known factor associated with treatment failure of chronic hepatitis
      C with interferon (IFN) and ribavirin. We studied the hepatocyte response in a
      model of steatosis at the transcriptome level and the antiviral action of IFN
      against hepatitis C virus (HCV) in this setting. In this study, we have shown
      that lipid loading (oleic acid and palmitic acid, OA:PA) of Huh-7 cells leads to
      increased expression of classical interferon-stimulated genes (ISGs) and NF
      kappabeta-dependent pro-inflammatory genes. A selective blocker of Toll-like
      receptor (TLR)2 signaling suppressed NF-kappabeta promoter activity by OA:PA,
      suggesting that free fatty acids (FFAs) act as a TLR2 pathogen-associated
      molecular pattern. Furthermore, in the presence of OA:PA, IFN stimulation and HCV
      infection (Jc1) increased ISG expression. Somewhat counterintuitive to the
      increase in ISGs, the anti-HCV activity of IFN was attenuated in the presence of
      OA:PA. Interestingly, the combination of OA:PA, HCV, and IFN-alpha stimulation
      resulted in a significant increase in CXCL8 protein production, a cytokine known
      to have anti-IFN modulating activity. Thus, in an in vitro model of steatosis,
      the FFAs OA and PA drive an NF-kappabeta-dependent inflammatory and ISG gene
      expression profile via TLR2 activation. Furthermore, FFA synergistically
      increases IFN-driven gene expression that may account for HCV treatment failure
      in vivo. 

PMID- 25588105
TI  - Time trend analysis of primary tumor resection for stage IV colorectal cancer:
      less surgery, improved survival.
AB  - IMPORTANCE: With the advent of effective modern chemotherapeutic and biologic
      agents, primary tumor resection for patients with stage IV colorectal cancer
      (CRC) may not be routinely necessary. OBJECTIVE: To evaluate the secular patterns
      of primary tumor resection use in stage IV CRC in the United States. DESIGN,
      SETTING, AND PARTICIPANTS: A retrospective cohort study using data from the
      National Cancer Institute's Surveillance, Epidemiology, and End Results CRC
      registry. Demographic and clinical factors were compared for 64,157 patients
      diagnosed with stage IV colon or rectal cancer from January 1, 1988, through
      December 31, 2010, who had undergone primary tumor resection and those who had
      not. Rates of primary tumor resection and median relative survival were
      calculated for each year. Joinpoint regression analysis was used to determine
      when a significant change in trend in the primary tumor resection rate had
      occurred. Logistic regression analysis was used to assess factors associated with
      primary tumor resection. MAIN OUTCOMES AND MEASURES: Difference in primary tumor
      resection rates over time. RESULTS: Of the 64,157 patients with stage IV CRC,
      43,273 (67.4%) had undergone primary tumor resection. The annual rate of primary
      tumor resection decreased from 74.5% in 1988 to 57.4% in 2010 (P<.001), and a
      significant annual percentage change occurred between 1998-2001 and 2001-2010 (
      0.41% vs -2.39%; P<.001). Factors associated with primary tumor resection were
      age younger than 50 years, female sex, being married, higher tumor grade, and
      presence of colon tumors. Median relative survival rate improved from 8.6% in
      1988 to 17.8% in 2009 (P<.001); the annual percentage change was 2.18% in 1988
      2001 and 5.43% in 1996-2009 (P<.001). CONCLUSIONS AND RELEVANCE: The majority of
      patients with stage IV CRC had undergone primary tumor resection but, beginning
      in 2001, a trend toward fewer primary tumor resections was seen. Despite the
      decreasing primary tumor resection rate, patient survival rates improved.
      However, primary tumor resection may still be overused, and current treatment
      practices lag behind evidence-based treatment guidelines.

PMID- 25588106
TI  - Metamorphosis of Galleria mellonella research.

PMID- 25588107
TI  - [Psychological distress, need for advice and utilization of professional help
      among students].
AB  - As a consequence of earlier investigations, which have demonstrated that 20-25%
      of the students report psychological distress, the knowledge of the need and the
      utilization of help resulting from psychological or social problems have to be
      improved. Data from 366 students were collected to determine the need for advice,
      the utilization of help and the occurrence of psychological symptoms (SCL-27) and
      interpersonal problems (IIP-C). Comparisons between students and the total
      population as well as between students with and without need for advice were
      made. 23,3% of the persons surveyed, expressed the wish to receive professional
      help. In comparison to the total population, the students reported more
      psychological symptoms and consulted less frequently a general practitioner or a
      gynecologist. Students with need for advice experienced more psychological
      distress. To encourage more of the distressed students to utilize professional
      help, the access to professional help should be facilitated. 

PMID- 25588108
TI  - Signaling proteins and pathways affected by flavonoids in leukemia cells.
AB  - Flavonoids are a class of plant secondary metabolites that are found ubiquitously
      in plants and in the human diet. Our objective is to investigate the
      antiproliferative effects of flavonoids (baicalein, luteolin, genistein,
      apigenin, scutellarin, galangin, chrysin, and naringenin) toward leukemia cells
      (HL-60, NB4, U937, K562, Jurkat) as well as the relationship between their
      antileukemic potencies and molecular structures. At the proteomic level, we
      evaluate the effects of different flavonoids on the expression levels of various
      proteins using Protein Pathway Array (PPA) technology. Our results showed a dose
      dependent cytotoxicity of flavonoids toward various types of leukemia cells. The
      results of PPA illustrated that flavonoids, such as baicalein, genistein, and
      scutellarin affected different proteins in different leukemia cell lines. Cell
      cycle regulatory proteins, such as CDK4, CDK6, Cyclin D1, Cyclin B1, p-CDC2, and
      p-RB were affected in different leukemia cells. Furthermore, we found that
      baicalein suppresses CDK4 and activates p-ERK in most leukemia cells; genistein
      mainly affects CDK4, p-ERK, p-CDC2, while scutellarin dysregulated the proteins,
      cell division control protein 42, Notch4, and XIAP. Collectively, a wide variety
      of dysregulation of key signaling proteins related to apoptosis and cell-cycle
      regulation contributes to the antileukemic properties of these flavonoids. 

PMID- 25588110
TI  - Host-guest complexation of a pyrogallol[4]arene derivative at the air-water
      interface.
AB  - The host-guest properties of acetylated aryl pyrogallol[4]arene (AcPy) were
      studied as a Langmuir monolayer at the air-water interface. The self-assembled
      Langmuir monolayer properties and interactions with monovalent and divalent metal
      cations were investigated using surface pressure- and surface potential-area
      isotherms, compression-decompression cycles, stability, and infrared reflection
      absorption spectroscopy (IRRAS). A favorable interaction is observed for
      complexation between acetylated aryl pyrogallol[4]arene with divalent calcium and
      cadmium cations, while no interaction is observed for monovalent sodium and
      potassium cations. Spectroscopic techniques allow for discrimination between
      cadmium and calcium complexation. 

PMID- 25588109
TI  - Electron transfer mediated electrochemical biosensor for microRNAs detection
      based on metal ion functionalized titanium phosphate nanospheres at attomole
      level.
AB  - MicroRNAs (miRNAs) have emerged as new candidates as diagnostic and prognostic
      biomarkers for the detection of a wide variety of cancers; thus, sensitive and
      selective detection of microRNAs is significant for early-phase cancer diagnosis
      and disease prevention. A novel and simple electrochemical miRNA biosensor was
      developed using Cd(2+)-modified titanium phosphate nanoparticles as signal unit,
      two DNA as capture probes, and Ru(NH3)6(3+) as electron transfer mediator. Large
      quantities of cadmium ions were mounted in titanium phosphate spheres to output
      the electrochemical signal. Because of the presence of Ru(NH3)6(3+) molecules
      that interacted with DNA base-pairs as electron wire, the electrochemical signal
      significantly increased more than 5 times. This approach achieved a wide dynamic
      linear range from 1.0 aM to 10.0 pM with an ultralow limit detection of 0.76 aM,
      exerting a substantial enhancement in sensitivity. Moreover, the proposed
      biosensor was sufficiently selective to discriminate the target miRNAs from
      homologous miRNAs and could be used for rapid and direct analysis of miRNAs in
      human serum. Therefore, this strategy provides a new and ultrasensitive platform
      for miRNA expression profiling in biomedical research and clinical diagnosis. 

PMID- 25588113
TI  - A multiplex fluorophore molecular beacon: detection of the target sequence using
      large Stokes shift and multiple emission signal properties.
AB  - We have developed a multiplex fluorophore molecular beacon () with fluorophores
      located at its end to produce unique FRET (Fluorescence Resonance Energy
      Transfer). It exhibited diverse fluorescence properties depending on the mixing
      pattern, such as large Stokes shift emission and multiple colors, namely, blue,
      green and red using one excitation wavelength. Our also worked in probing a
      target perfect matched sequence with exonuclease III. 

PMID- 25588115
TI  - Nondestructive identification of dye mixtures in polyester and cotton fibers
      using raman spectroscopy and ultraviolet-visible (UV-Vis) microspectrophotometry.
AB  - Presented in this paper is an assessment of the applicability of Raman
      spectroscopy and microspectrophotometry (MSP) in visible and ultraviolet light
      (UV-Vis) in the examination of textile fibers dyed with mixtures of synthetic
      dyes. Fragments of single polyester fibers, stained with ternary mixtures of
      disperse dyes in small mass concentrations, and fragments of single cotton
      fibers, dyed with binary or ternary mixtures of reactive dyes, were subjected to
      the study. Three types of excitation sources, 514, 633, and 785 nm, were used
      during Raman examinations, while the MSP study was conducted in the 200 to 800 nm
      range. The results indicate that the capabilities for discernment of dye mixtures
      are similar in the spectroscopic methods that were employed. Both methods have a
      limited capacity to distinguish slightly dyed polyester fiber; additionally, it
      was found that Raman spectroscopy enables identification of primarily the major
      components in dye mixtures. The best results, in terms of the quality of Raman
      spectra, were obtained using an excitation source from the near infrared. MSP
      studies led to the conclusion that polyester testing should be carried out in the
      range above 310 nm, while for cotton fibers there is no limitation or restriction
      of the applied range. Also, MSP UV-Vis showed limited possibilities for
      discriminatory analysis of cotton fibers dyed with a mixture of reactive dyes,
      where the ratio of the concentration of the main dye used in the dyeing process
      to minor dye was higher than four. The results presented have practical
      applications in forensic studies, inter alia. 

PMID- 25588112
TI  - Association between pre-pregnancy depression/anxiety symptoms and hypertensive
      disorders of pregnancy.
AB  - BACKGROUND: Depression and anxiety symptoms have been linked with hypertensive
      disorders during pregnancy, but these associations have not been fully
      elucidated. Our objective was to consider hypertension in pregnancy and its
      subtypes (chronic hypertension, gestational hypertension, preeclampsia) and
      evaluate whether the proximity of psychological symptoms to pregnancy informs any
      associations observed. METHODS: Pregnancy Outcomes and Community Health Study
      participants who provided interview data at enrollment (16-27 weeks' gestation)
      and whose hypertensive disorder status was abstracted from medical records were
      eligible for inclusion (n=1371). Maternal history of depression/anxiety symptoms
      at four time points in the life course were ascertained via self-report at
      enrollment (i.e., lifetime history, 1 year prior to pregnancy, since last
      menstrual period, and past week). Weighted logistic regression models were used
      to examine depression/anxiety symptom measures in relation to hypertensive
      disorders (overall) and subtype. RESULTS: Following adjustment for maternal
      sociodemographic factors, smoking, and prepregnancy body mass index, prepregnancy
      depression or anxiety symptoms (i.e., lifetime history and 1 year prior to
      pregnancy) were associated with hypertensive disorders during pregnancy. Subtype
      analyses revealed that these associations were driven primarily by chronic
      hypertension (adjusted odds ratios=2.7-3.5). Preeclampsia accompanied by preterm
      delivery was also linked to women's lifetime history of depression symptoms (odds
      ratio=2.3, 95% confidence interval 1.0-5.2). CONCLUSION: Our results suggest that
      the link between maternal chronic hypertension and depression/anxiety symptoms
      precedes pregnancy. In addition, prepregnancy history of depression/anxiety
      symptoms may be considered part of a risk profile for preterm preeclampsia.

PMID- 25588111
TI  - Beyond the histone tale: HP1alpha deregulation in breast cancer epigenetics.
AB  - Heterochromatin protein 1alpha (HP1alpha) encoded from the CBX5-gene is an
      evolutionary conserved protein that binds histone H3 di- or tri-methylated at
      position lysine 9 (H3K9me2/3), a hallmark for heterochromatin, and has an
      essential role in forming higher order chromatin structures. HP1alpha has diverse
      functions in heterochromatin formation, gene regulation, and mitotic progression,
      and forms complex networks of gene, RNA, and protein interactions. Emerging
      evidence has shown that HP1alpha serves a unique biological role in breast cancer
      related processes and in particular for epigenetic control mechanisms involved in
      aberrant cell proliferation and metastasis. However, how HP1alpha deregulation
      plays dual mechanistic functions for cancer cell proliferation and metastasis
      suppression and the underlying cellular mechanisms are not yet comprehensively
      described. In this paper we provide an overview of the role of HP1alpha as a new
      sight of epigenetics in proliferation and metastasis of human breast cancer. This
      highlights the importance of addressing HP1alpha in breast cancer diagnostics and
      therapeutics. 

PMID- 25588116
TI  - Silk macromolecules with amino acid-poly(ethylene glycol) grafts for controlling
      layer-by-layer encapsulation and aggregation of recombinant bacterial cells.
AB  - This study introduces double-brush designs of functionalized silk
      polyelectrolytes based upon regenerated silk fibroin (SF), which is modified with
      poly-L-lysine (SF-PLL), poly-L-glutamic acid (SF-PGA), and poly(ethylene glycol)
      (PEG) side chains with different grafting architecture and variable amino acid
      PEG graft composition for cell encapsulation. The molecular weight of poly amino
      acids (length of side chains), molecular weight and degree of PEG grafting (D)
      were varied in order to assess the formation of cytocompatible and robust layer
      by-layer (LbL) shells on two types of bacterial cells (Gram-negative and Gram
      positive bacteria). We observed that shells assembled with charged polycationic
      amino acids adversely effected the properties of microbial cells while promoting
      the formation of large cell aggregates. In contrast, hydrogen-bonded shells with
      high PEG grafting density were the most cytocompatible, while promoting formation
      of stable colloidal suspensions of individual cell encapsulates. The stability to
      degradation of silk shells (under standard cell incubation procedure) was related
      to the intrinsic properties of thermodynamic bonding forces, with shells based on
      electrostatic interactions having stronger resistance to deterioration compared
      to pure hydrogen-bonded silk shells. By optimizing the charge density of silk
      polyelectrolytes brushes, as well as the length and the degree of PEG side
      grafts, robust and cytocompatible cell coatings were engineered that can control
      aggregation of cells for biosensor devices and other potential biomedical
      applications.

PMID- 25588114
TI  - Synthesis, stereochemical analysis, and derivatization of myricanol provide new
      probes that promote autophagic tau clearance.
AB  - We previously discovered that one specific scalemic preparation of myricanol (1),
      a constituent of Myrica cerifera (bayberry/southern wax myrtle) root bark, could
      lower the levels of the microtubule-associated protein tau (MAPT). The
      significance is that tau accumulates in a number of neurodegenerative diseases,
      the most common being Alzheimer's disease (AD). Herein, a new synthetic route to
      prepare myricanol using a suitable boronic acid pinacol ester intermediate is
      reported. An X-ray crystal structure of the isolated myricanol (1) was obtained
      and showed a co-crystal consisting of (+)-aR,11S-myricanol (2) and (-)-aS,11R
      myricanol (3) coformers. Surprisingly, 3, obtained from chiral separation from 1,
      reduced tau levels in both cultured cells and ex vivo brain slices from a mouse
      model of tauopathy at reasonable mid-to-low micromolar potency, whereas 2 did
      not. SILAC proteomics and cell assays revealed that 3 promoted tau degradation
      through an autophagic mechanism, which was in contrast to that of other tau
      lowering compounds previously identified by our group. During the course of
      structure-activity relationship (SAR) development, we prepared compound 13 by
      acid-catalyzed dehydration of 1. 13 had undergone an unexpected structural
      rearrangement through the isomyricanol substitution pattern (e.g., 16), as
      verified by X-ray structural analysis. Compound 13 displayed robust tau-lowering
      activity, and, importantly, its enantiomers reduced tau levels similarly.
      Therefore, the semisynthetic analogue 13 provides a foundation for further
      development as a tau-lowering agent without its SAR being based on chirality. 

PMID- 25588117
TI  - Perturbation factors in the clinical handling of a fiber-coupled Raman probe for
      cutaneous in vivo diagnostic Raman spectroscopy.
AB  - The application of fiber-coupled Raman probes for the discrimination of cancerous
      and normal skin has the advantage of a non-invasive in vivo application, easy
      clinical handling, and access to the majority of body sites, which would
      otherwise be limited by stationary Raman microscopes. Nevertheless, including
      optical fibers and miniaturizing optical components, as well as measuring in
      vivo, involves the sensibility to external perturbation factors that could
      introduce artifacts to the acquired Raman spectra and thereby potentially reduce
      classification performance. In this study, typical perturbation factors of Raman
      measurements with a Raman fiber probe, optimized for clinical in vivo
      discrimination of skin cancer, were investigated experimentally. Measurements
      were performed under standardized conditions in clinical settings in vivo on
      human skin, as well as ex vivo on porcine ears. Raman spectra were analyzed in
      the fingerprint region between 1150 and 1730 cm(-1) using principal component
      analysis. The largest artifacts in the Raman spectra were found in measurements
      performed under the influence of strong ambient light conditions as well as after
      miscellaneous pre-treatments to the skin, such as use of a permanent marker or a
      sunscreen. Minor influences were also found in measurements using H2O immersion
      and when varying the probe contact force. The effect of reasonable variation of
      the fiber-bending radius was found to be of negligible impact. The influence of
      measurements on hairy or sun-exposed body sites, as well as inter-subject
      variation, was also investigated. The presented results may serve as a guide to
      avoid negative effects during the process of data acquisition and so avoid
      misclassification in tumor discrimination. 

PMID- 25588118
TI  - Modeling nitrous oxide production and reduction in soil through explicit
      representation of denitrification enzyme kinetics.
AB  - An enzyme-explicit denitrification model with representations for pre- and de
      novo synthesized enzymes was developed to improve predictions of nitrous oxide
      (N2O) accumulations in soil and emissions from the surface. The metabolic model
      of denitrification is based on dual-substrate utilization and Monod growth
      kinetics. Enzyme synthesis/activation was incorporated into each sequential
      reduction step of denitrification to regulate dynamics of the denitrifier
      population and the active enzyme pool, which controlled the rate function.
      Parameterizations were developed from observations of the dynamics of N2O
      production and reduction in soil incubation experiments. The model successfully
      reproduced the dynamics of N2O and N2 accumulation in the incubations and
      revealed an important regulatory effect of denitrification enzyme kinetics on the
      accumulation of denitrification products. Pre-synthesized denitrification enzymes
      contributed 20, 13, 43, and 62% of N2O that accumulated in 48 h incubations of
      soil collected from depths of 0-5, 5-10, 10-15, and 15-25 cm, respectively. An
      enzyme activity function (E) was defined to estimate the relative concentration
      of active enzymes and variation in response to environmental conditions. The
      value of E allows for activities of pre-synthesized denitrification enzymes to be
      differentiated from de novo synthesized enzymes. Incorporating explicit
      representations of denitrification enzyme kinetics into biogeochemical models is
      a promising approach for accurately simulating dynamics of the production and
      reduction of N2O in soils. 

PMID- 25588119
TI  - Tree species composition affects the abundance of rowan (Sorbus aucuparia L.) in
      urban forests in Finland.
AB  - Recent studies have shown a considerable increase in the abundance of rowan
      (Sorbus aucuparia) saplings in urban forests in Finland, yet the reasons for this
      increase are not well understood. Here we investigated whether canopy cover or
      tree species composition, i.e., the basal areas of different tree species in
      Norway spruce dominated urban forests, affects the abundances of rowan seedlings,
      saplings and trees. Altogether 24 urban forest patches were investigated. We
      sampled the number of rowan and other saplings, and calculated the basal areas of
      trees. We showed that rowan abundance was affected by tree species composition.
      The basal area of rowan trees (>= 5 cm in diameter at breast height, dbh)
      decreased with increasing basal area of Norway spruce, while the cover of rowan
      seedlings increased with an increase in Norway spruce basal area. However, a
      decrease in the abundance of birch (Betula pendula) and an increase in the broad
      leaved tree group (Acer platanoides, Alnus glutinosa, Alnus incana, Amelanchier
      spicata, Prunus padus, Quercus robur, Rhamnus frangula and Salix caprea)
      coincided with a decreasing number of rowans. Furthermore, rowan saplings were
      scarce in the vicinity of mature rowan trees. Although it seems that tree species
      composition has an effect on rowan, the relationship between rowan saplings and
      mature trees is complex, and therefore we conclude that regulating tree species
      composition is not an easy way to keep rowan thickets under control in urban
      forests in Finland.

PMID- 25588120
TI  - Recovery of bulk proton magnetization and sensitivity enhancement in ultrafast
      magic-angle spinning solid-state NMR.
AB  - The sensitivity of solid-state NMR experiments is limited by the proton
      magnetization recovery delay and by the duty cycle of the instrument. Ultrafast
      magic-angle spinning (MAS) can improve the duty cycle by employing experiments
      with low-power radio frequency (RF) irradiation which reduce RF heating. On the
      other hand, schemes to reduce the magnetization recovery delay have been proposed
      for low MAS rates, but the enhancements rely on selective transfers where the
      bulk of the (1)H magnetization pool does not contribute to the transfer. We
      demonstrate here that significant sensitivity enhancements for selective and
      broadband experiments are obtained at ultrafast MAS by preservation and recovery
      of bulk (1)H magnetization. We used [(13)C, (15)N]-labeled glutamine as a model
      compound, spinning in a 1.3 mm rotor at a MAS frequency of 65 kHz. Using low
      power (1)H RF (13.4 kHz), we obtain efficient (1)H spin locking and (1)H-(13)C
      decoupling at ultrafast MAS. As a result, large amounts of (1)H magnetization,
      from 35% to 42% of the initial polarization, are preserved after cross
      polarization and decoupling. Restoring this magnetization to the longitudinal
      axis using a flip-back pulse leads to an enhancement of the sensitivity, an
      increase ranging from 14% to 21% in the maximal achievable sensitivity regime and
      from 24% to 50% in the fast pulsing regime, and to a shortening of the optimal
      recycling delay to 68% of its original duration. The analysis of the recovery and
      sensitivity curves reveals that the sensitivity gains do not rely on a selective
      transfer where few protons contribute but rather on careful conservation of bulk
      (1)H magnetization. This makes our method compatible with broadband experiments
      and uniformly labeled materials, in contrast to the enhancement schemes proposed
      for low MAS. We tested seven different cross-polarization schemes and determined
      that recovery of bulk (1)H magnetization is a general method for sensitivity
      enhancement. The physical insight gained about the behavior of proton
      magnetization sharing under spin lock will be helpful to break further
      sensitivity boundaries, when even higher external magnetic fields and faster
      spinning rates are employed. 

PMID- 25588121
TI  - Metabolic profiling of plant extracts using direct-injection electrospray
      ionization mass spectrometry allows for high-throughput phenotypic
      characterization according to genetic and environmental effects.
AB  - In comparison to the exponential increase of genotyping methods, phenotyping
      strategies are lagging behind in agricultural sciences. Genetic improvement
      depends upon the abundance of quantitative phenotypic data and the statistical
      partitioning of variance into environmental, genetic, and random effects. A
      metabolic phenotyping strategy was adapted to increase sample throughput while
      saving reagents, reducing cost, and simplifying data analysis. The chemical
      profiles of stem extracts from maize plants grown under low nitrogen (LN) or
      control trial (CT) were analyzed using optimized protocols for direct-injection
      electrospray ionization mass spectrometry (DIESI-MS). Specific ions significantly
      decreased or increased because of environmental (LN versus CT) or genotypic
      effects. Biochemical profiling with DIESI-MS had a superior cost-benefit compared
      to other standard analytical technologies (e.g., ultraviolet, near-infrared
      reflectance spectroscopy, high-performance liquid chromatography, and gas
      chromatography with flame ionization detection) routinely used for plant
      breeding. The method can be successfully applied in maize, strawberry, coffee,
      and other crop species. 

PMID- 25588122
TI  - Procedures for the Comparative Testing of Noninvasive Neuroassessment Devices.
AB  - A sequential process for comparison testing of noninvasive neuroassessment
      devices is presented. Comparison testing of devices in a clinical population
      should be preceded by computational research and reliability testing with healthy
      populations, as opposed to proceeding immediately to testing with clinical
      participants. A five-step process is outlined as follows: 1. Complete a
      preliminary literature review identifying candidate measures. 2. Conduct
      systematic simulation studies to determine the computational properties and data
      requirements of candidate measures. 3. Establish the test-retest reliability of
      each measure in a healthy comparison population and the clinical population of
      interest. 4. Investigate the clinical validity of reliable measures in
      appropriately defined clinical populations. 5. Complete device usability
      assessment (weight, simplicity of use, cost effectiveness, ruggedness) only for
      devices and measures that are promising after steps 1 through 4 are completed.
      Usability may be considered throughout the device evaluation process but such
      considerations are subordinate to the higher priorities addressed in steps 1
      through 4. 

PMID- 25588124
TI  - Modular and highly stereoselective approach to all-carbon tetrasubstituted
      alkenes.
AB  - A modular and completely stereoselective approach for the construction of all
      carbon tetrasubstituted alkenes is described. It is based on the three-fold,
      sequential metal-catalyzed, cross-coupling functionalization of simple
      enolphosphate dibromide templates with carbon nucleophiles, affording
      tetrasubstituted alkenes as single isomers. 

PMID- 25588123
TI  - Changes in drug coverage generosity and untreated serious mental illness:
      transitioning from Medicaid to Medicare Part D.
AB  - IMPORTANCE: More than 1 in 5 disabled people with dual Medicare-Medicaid
      enrollment have schizophrenia or a bipolar disorder (ie, a serious mental
      illness). The effect of their transition from Medicaid drug coverage, which
      varies in generosity across states, to the Medicare Part D drug benefit is
      unknown. Many thousands make this transition annually. OBJECTIVES: To determine
      the effect of transitioning from Medicaid drug benefits to Medicare Part D on
      medication use by patients with a serious mental illness and to determine the
      influence of Medicaid drug caps. DESIGN, SETTING, AND PARTICIPANTS: In time
      series analysis of continuously enrolled patient cohorts (2004-2007), we
      estimated changes in medication use before and after transitioning to Part D,
      comparing states that capped monthly prescription fills with states with no
      prescription limits. We used Medicaid and Medicare claims from a 5% national
      sample of community-dwelling, nonelderly disabled dual enrollees with
      schizophrenia (n = 5554) or bipolar disorder (n = 3675). MAIN OUTCOMES AND
      MEASURES: Psychotropic treatments included antipsychotics for schizophrenia and
      antipsychotics, anticonvulsants, and lithium for bipolar disorder. We measured
      monthly rates of untreated illness, intensity of treatment, and overall
      prescription medication use. RESULTS: Prior to Part D, the prevalence of
      untreated illness among patients with a bipolar disorder was 30.0% in strict-cap
      states and 23.8% in no-cap states. In strict-cap states, the proportion of
      untreated patients decreased by 17.2% (relatively) 1 year after Part D, whereas
      there was no change in the proportion of untreated patients in no-cap states. For
      patients with schizophrenia, the untreated rate (20.6%) did not change in strict
      cap states, yet it increased by 23.3% (from 11.6%) in no-cap states. Overall
      medication use increased substantially after Part D in strict-cap states:
      prescription fills were 35.5% higher among patients with a bipolar disorder and
      17.7% higher than predicted among schizophrenic patients; overall use in no-cap
      states was unchanged in both cohorts. CONCLUSIONS AND RELEVANCE: The effects of
      transitioning from Medicaid to Medicare Part D on essential treatment of serious
      mental illness vary by state. Transition to Part D in states with strict drug
      benefit limits may reduce rates of untreated illness among patients with bipolar
      disorders, who have high levels of overall medication use. Access to
      antipsychotic treatment may decrease after Part D for patients with a serious
      mental illness living in states with relatively generous uncapped Medicaid
      coverage.

PMID- 25588125
TI  - Emergence of Colistin- and Carbapenem-Resistant Acinetobacter baumannii ST2
      Clinical Isolate in Algeria: First Case Report.
AB  - AIM: The aim of this study was to investigate the prevalence and the mechanisms
      of carbapenem and colistin resistance in Acinetobacter baumannii clinical
      isolates in an Algerian hospital. RESULTS: Twelve isolates were collected between
      October 2013 and March 2014. All isolates were resistant to almost all
      antibiotics tested with a high-level resistance to imipenem (minimum inhibitory
      concentrations [MICs] >32 mg/L) with one strain showing resistance to colistin
      (MIC=16 mg/L). The results of the modified Hodge test and the modified Carba NP
      test were positive for all isolates. Besides, the activity of beta-lactamases was
      inhibited by EDTA in only two isolates. All the 12 isolates contained the
      naturally occurring blaOXA-51-like gene. Ten of them harbored the OXA beta
      lactamases: blaOXA-23 (six isolates) and blaOXA-24 (four isolates) genes, while
      two isolates were positive for blaNDM-1 gene. The colistin-resistant isolate
      producing OXA-24 enzyme harbored a single mutation in the pmrB gene. Multilocus
      sequence typing demonstrated that the 12 isolates belonged to 2 clones: 10 to ST2
      and 2 to ST85. CONCLUSIONS: Here, we describe the mechanisms of carbapenem
      resistance and we report the first colistin and carbapenemase-producing A.
      baumannii clinical isolate from a patient in Algeria.

PMID- 25588127
TI  - Copper(I)-catalyzed regioselective amination of N-aryl imines using TMSN3 and
      TBHP: a route to substituted benzimidazoles.
AB  - A novel and efficient copper-catalyzed amination of N-aryl imines is described.
      This one-pot, multicomponent reaction, in which imine acts as a directing group
      by chelating to the metal center, affords a potential route for the
      transformation of the commercial aryl amines, aldehydes, and azides into valuable
      benzimidazole structural units with wide substrate scope and diversity. The
      synthetic and mechanistic aspects are presented. 

PMID- 25588126
TI  - Fabrication and characterization of the nano-composite of whey protein
      hydrolysate chelated with calcium.
AB  - The nano-composites of whey protein hydrolysate (WPH) chelated with calcium were
      fabricated in aqueous solution at 30  degrees C for 20 min, with the ratio of
      hydrolysate to calcium 15 : 1 (w/w). UV scanning spectroscopy, fluorescent
      spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering
      and atomic force microscopy were applied to characterize the structure of the WPH
      calcium chelate. The nano-composites showed the successful incorporation of
      calcium into the WPH, indicating the interaction between calcium and WPH. The
      chelation of calcium ions to WPH caused molecular folding and aggregation which
      led to the formation of a WPH-calcium chelate of nanoparticle size, and the
      principal sites of calcium-binding corresponded to the carboxyl groups and
      carbonyl groups of WPH. The WPH-calcium chelate demonstrated excellent stability
      and absorbability under both acidic and basic conditions, which was beneficial
      for calcium absorption in the gastrointestinal tract of the human body. Moreover,
      the calcium absorption of the WPH-calcium chelate on Caco-2 cells was
      significantly higher than those of calcium gluconate and CaCl2 in vitro,
      suggesting the possible increase in calcium bioavailability. The findings suggest
      that the WPH-calcium chelate has the potential in making dietary supplements for
      improving bone health of the human body.

PMID- 25588128
TI  - Membrane bioreactor wastewater treatment plants reveal diverse yeast and protist
      communities of potential significance in biofouling.
AB  - The yeast community was studied in a municipal full-scale membrane bioreactor
      wastewater treatment plant (MBR-WWTP). The unexpectedly high diversity of yeasts
      indicated that the activated sludge formed a suitable environment for them to
      proliferate, with cellular concentrations of 2.2 +/- 0.8 * 10(3) CFU ml(-1).
      Sixteen species of seven genera were present in the biological reactor, with
      Ascomycetes being the most prevalent group (93%). Most isolates were able to grow
      in a synthetic wastewater medium, adhere to polyethylene surfaces, and develop
      biofilms of variable complexity. The relationship between yeast populations and
      the protists in the MBR-WWTP was also studied, revealing that some protist
      species preyed on and ingested yeasts. These results suggest that yeast
      populations may play a role in the food web of a WWTP and, to some extent,
      contribute to membrane biofouling in MBR systems.

PMID- 25588129
TI  - Efficient approach to improving the flame retardancy of poly(vinyl alcohol)/clay
      aerogels: incorporating piperazine-modified ammonium polyphosphate.
AB  - Ammonium polyphosphates (APP) modified with piperazine (PA-APP) was used to
      improve the flame retardancy of poly(vinyl alcohol) (PVA)/montmorillonite (MMT)
      aerogels, which were prepared via an environmentally friendly freeze-drying
      method. The thermal stabilities of the samples were evaluated by
      thermogravimetric analysis (TG); the flammability behaviors of samples were
      investigated by limiting oxygen index (LOI), vertical burning test (UL-94) and
      cone calorimeter (CC) tests. TG test results showed that the 5% weight loss
      temperature (T5%) of PVA/MMT/PA-APP was 10  degrees C higher than that of
      PVA/MMT/APP. In combustion testing, all of PVA/MMT/PA-APP aerogels achieved V-0
      ratings and have a higher LOI values than the unmodified PVA/MMT aerogel.
      Moreover, the aerogel with 1% PA-APP5, which means that the content of piperazine
      is 5% in PA-APP, decreased the cone calorimetry THR value to 5.71 MJ/m(2), and
      increased the char residue to 52%. The compressive modulus of PVA/MMT/PA-APP was
      increased by 93.4% compared with PVA/MMT/APP because of the increase in
      interfacial adhesion between matrix and PA-APP fillers. The densities of the
      PVA/MMT/PA-APP samples were slightly lower than those of the unmodified aerogels
      because of reduced shrinkage in the presence of PA-APP. All the tests results
      indicated that the incorporation of PA-APP not only improved the thermal
      stability and flame retardancy of aerogels but also maintained their mechanical
      properties. 

PMID- 25588132
TI  - Introducing the medical care blog.

PMID- 25588131
TI  - Fatty acid hydrolysis of acyl marinobactin siderophores by Marinobacter acylases.
AB  - The marine bacteria Marinobacter sp. DS40M6 and Marinobacter nanhaiticus D15-8W
      produce a suite of acyl peptidic marinobactin siderophores to acquire iron under
      iron-limiting conditions. During late-log phase growth, the marinobactins are
      hydrolyzed to form the marinobactin headgroup with release of the corresponding
      fatty acid tail. The bntA gene, a homologue of the Pseudomonas aeruginosa
      pyoverdine acylase gene, pvdQ, was identified from Marinobacter sp. DS40M6. A
      bntA knockout mutant of Marinobacter sp. DS40M6 produced the suite of acyl
      marinobactins A-E, without the usual formation of the marinobactin headgroup.
      Another marinobactin-producing species, M. nanhaiticus D15-8W, is predicted to
      have two pvdQ homologues, mhtA and mhtB. MhtA and MhtB have 67% identical amino
      acid sequences. MhtA catalyzes hydrolysis of the apo-marinobactin siderophores as
      well as the quorum sensing signaling molecule, dodecanoyl-homoserine lactone. In
      contrast to hydrolysis of the suite of apo-marinobactins by MhtA, hydrolysis of
      the iron(III)-bound marinobactins was not observed. 

PMID- 25588130
TI  - Effect of supplementation of water-soluble vitamins on oxidative stress and blood
      pressure in prehypertensives.
AB  - The objective of the study was to evaluate the effect of water-soluble vitamins
      on oxidative stress and blood pressure in prehypertensives. Sixty
      prehypertensives were recruited and randomized into 2 groups of 30 each. One
      group received water-soluble vitamins and the other placebo for 4 months. Further
      increase in blood pressure was not observed in the vitamin group which increased
      significantly in the placebo group at the end of 4 months. Malonedialdehyde and
      protein carbonylation were reduced during the course of treatment with vitamins
      whereas in the placebo group there was an increase in the level of
      malondialdehyde. In conclusion, supplementation of water-soluble vitamins in
      prehypertension reduces oxidative stress and its progression to hypertension.

PMID- 25588133
TI  - The cost-effectiveness of pay-for-performance: a multidimensional approach to
      analysis.

PMID- 25588134
TI  - How effective is health coaching in reducing health services expenditures?
AB  - BACKGROUND: Health coaching interventions aim to identify high-risk enrollees and
      encourage them to play a more proactive role in improving their health, improve
      their ability to navigate the health care system, and reduce costs. OBJECTIVES:
      Evaluate the effect of health coaching on inpatient, emergency room, outpatient,
      and prescription drug expenditures. RESEARCH DESIGN: Quasiexperimental pre-post
      design. Health coaching participants were identified over the 2-year time period
      2009-2010. Propensity scores facilitated matching eligible participants and
      nonparticipating controls on a one-to-one basis using nearest kernel techniques.
      Difference in differences logistic and generalized linear models addressed the
      impact of health coaching on the probability of incurring costs and levels of
      inpatient, emergency room, outpatient, and prescription drug expenditures,
      respectively. MEASURES: Administrative claims data were used to analyze health
      services expenditures preparticipation and post health coaching participation
      time periods. RESULTS: Of the 6940 health coaching participants, 1161
      participated for at least 4 weeks and had a minimum of 6 months of claims data
      preparticipation and postparticipation. Although the probability of incurring
      costs and expenditure levels for emergency room services were not affected, the
      probability of incurring inpatient expenditures and levels of outpatient and
      total costs for health coaching participants fell significantly from
      preparticipation to postparticipation relative to controls. Estimated outpatient
      and total cost savings were $286 and $412 per person per month, respectively.
      CONCLUSIONS: Health coaching led to significant reductions in outpatient and
      total expenditures for high-risk plan enrollees. Future studies analyzing both
      health outcomes and claims data are needed to assess the cost-effectiveness of
      health coaching in specific populations.

PMID- 25588136
TI  - A systematic review of intervention studies to prevent hospitalizations of
      community-dwelling older adults with dementia.
AB  - OBJECTIVES: To conduct a systematic literature review to determine if there were
      any intervention strategies that had any measurable effect on acute-care
      hospitalizations among community-dwelling adults with dementia. DESIGN: Studies
      were identified by a professional research librarian and content experts.
      SETTING: Community dwelling. PARTICIPANTS: Participants were diagnosed with
      dementia, severity ranging from mild to severe, and were recruited from health
      care and community agencies. MEASUREMENTS: A study met the inclusion criteria if
      it: (a) was published in English; (b) included a control or comparison group; (c)
      published outcome data from the intervention under study; (d) reported
      hospitalization as one of the outcomes; (e) included community-dwelling older
      adults; and (f) enrolled participants with dementia. Ten studies met all
      inclusion criteria. RESULTS: Of the 10 studies included, most assessed health
      services use (ie, hospitalizations) as a secondary outcome. Participants were
      recruited from a range of health care and community agencies, and most were
      diagnosed with dementia with severity ratings ranging from mild to severe. Most
      intervention strategies consisted of face-to-face assessments of the persons
      living with dementia, their caregivers, and the development and implementation of
      a care plan. A significant reduction in hospital admissions was not found in any
      of the included studies, although 1 study did observe a reduction in hospital
      days. CONCLUSIONS: The majority of studies included hospitalizations as a
      secondary outcome. Only 1 intervention was found to have an effect on
      hospitalizations. Future work would benefit from strategies specifically designed
      to reduce and prevent acute hospitalizations in persons with dementia.

PMID- 25588135
TI  - The role of technical advances in the adoption and integration of patient
      reported outcomes in clinical care.
AB  - BACKGROUND: Patient-reported outcomes (PROs) are gaining recognition as key
      measures for improving the quality of patient care in clinical care settings.
      Three factors have made the implementation of PROs in clinical care more
      feasible: increased use of modern measurement methods in PRO design and
      validation, rapid progression of technology (eg, touchscreen tablets, Internet
      accessibility, and electronic health records), and greater demand for measurement
      and monitoring of PROs by regulators, payers, accreditors, and professional
      organizations. As electronic PRO collection and reporting capabilities have
      improved, the challenges of collecting PRO data have changed. OBJECTIVES: To
      update information on PRO adoption considerations in clinical care, highlighting
      electronic and technical advances with respect to measure selection, clinical
      workflow, data infrastructure, and outcomes reporting. METHODS: Five practical
      case studies across diverse health care settings and patient populations are used
      to explore how implementation barriers were addressed to promote the successful
      integration of PRO collection into the clinical workflow. The case studies
      address selecting and reporting of relevant content, workflow integration,
      previsit screening, effective evaluation, and electronic health record
      integration. CONCLUSIONS: These case studies exemplify elements of well-designed
      electronic systems, including response automation, tailoring of item selection
      and reporting algorithms, flexibility of collection location, and integration
      with patient health care data elements. They also highlight emerging logistical
      barriers in this area, such as the need for specialized technological and
      methodological expertise, and design limitations of current electronic data
      capture systems.

PMID- 25588138
TI  - Cesarean 10-group classification: a tool for clinical management of the delivery
      ward.
AB  - AIM: Aim of the present study was to evaluate 10-group Robson classification for
      delivery ward clinical management. METHODS: To evaluate cesarean section (C
      section) rate following the implementation firstly of recommendations, and then
      of 10-group reporting and medical audit, a retrospective cohort study was
      performed including all women who gave birth in the years 2001, 2006 and 2010.
      Data were analyzed by means of 10-group classification. RESULTS: C-section rate
      was 27.5% in 2001, 31.1% in 2006, and 30.5% in 2010. Ten-group analysis showed
      that from 2001 to 2006 group 1-2 size increased from 27.6% to 42.5% (P<0.01), and
      contribution to the overall cesarean rate from 22.3% to 29.9% (P<0.01), whereas
      the group 1 C-section sub-rate was reduced from 19.6% to 13.5% (P<0.05). Previous
      cesarean increased from 9.2% to 11.6% (P<0.05). Delivery ward 10-group monitoring
      showed that from January to May 2010 the C-section rate was consistently above
      30%. The audit was started and the causes were analyzed. Subsequently, C-section
      rate dropped to the actual 30.5%. CONCLUSION: Ten-group analysis showed that the
      2006 cesarean rate increase was related to a significant shift in obstetric
      population toward groups 5 to 9 at higher risk of C-section, whereas after
      recommendation implementation a significant reduction of C-section subrates was
      observed in groups 1, 2a, 3, 4a, and 10 which represented more than 80% of the
      hospital population. In 2010, 10-group monitoring of the cesarean subrates
      stabilized the C-section rate. Ten-group analysis should be implemented in
      clinical practice to control delivery ward clinical management. It only requires
      the involvement of a clinical manager and of a midwife for data collection.

PMID- 25588137
TI  - Increasing BCI communication rates with dynamic stopping towards more practical
      use: an ALS study.
AB  - OBJECTIVE: The P300 speller is a brain-computer interface (BCI) that can possibly
      restore communication abilities to individuals with severe neuromuscular
      disabilities, such as amyotrophic lateral sclerosis (ALS), by exploiting elicited
      brain signals in electroencephalography (EEG) data. However, accurate spelling
      with BCIs is slow due to the need to average data over multiple trials to
      increase the signal-to-noise ratio (SNR) of the elicited brain signals.
      Probabilistic approaches to dynamically control data collection have shown
      improved performance in non-disabled populations; however, validation of these
      approaches in a target BCI user population has not occurred. APPROACH: We have
      developed a data-driven algorithm for the P300 speller based on Bayesian
      inference that improves spelling time by adaptively selecting the number of
      trials based on the acute SNR of a user's EEG data. We further enhanced the
      algorithm by incorporating information about the user's language. In this current
      study, we test and validate the algorithms online in a target BCI user
      population, by comparing the performance of the dynamic stopping (DS) (or early
      stopping) algorithms against the current state-of-the-art method, static data
      collection, where the amount of data collected is fixed prior to online
      operation. MAIN RESULTS: Results from online testing of the DS algorithms in
      participants with ALS demonstrate a significant increase in communication rate as
      measured in bits/min (100-300%), and theoretical bit rate (100-550%), while
      maintaining selection accuracy. Participants also overwhelmingly preferred the DS
      algorithms. SIGNIFICANCE: We have developed a viable BCI algorithm that has been
      tested in a target BCI population which has the potential for translation to
      improve BCI speller performance towards more practical use for communication.

PMID- 25588139
TI  - Integrating the pathogenesis of spondyloarthritis: gut and joint united?
AB  - PURPOSE OF REVIEW: The association between spondyloarthritis (SpA) and
      inflammatory bowel disease (IBD) is well known. Additionally, about half of SpA
      patients show microscopic gut inflammation. Substantial progress has been made in
      understanding the pathogenesis of SpA and IBD, with new therapeutic targets for
      either of them in clinical development. RECENT FINDINGS: Microscopic gut
      inflammation was found in early forms of SpA in about 50% of cases and is
      associated with age, sex, disease activity and degree of MRI inflammation on
      sacroiliac joints. Although prospective follow-up data in men and murine animal
      studies show a parallelism between gut and joint evolution in SpA, therapeutic
      outcomes are not always the same in SpA and IBD. These differences can be
      ascribed to differences in not only the cytokine pathways and cells involved in
      disease, tissue localization and environmental factors but also in
      pharmacokinetics and biodistribution. SUMMARY: A significant amount of data all
      point in the direction of arthritis and gut inflammation being pathogenetically
      closely linked in the SpA concept. However, when it comes to therapeutic
      effectiveness, the gut and the joints do not always react in the same way. These
      differences in therapeutic effect could be attributed to the different ways in
      which cytokine pathways are involved in SpA and IBD.

PMID- 25588141
TI  - Assessment of microcirculation by contrast-enhanced ultrasound: a new approach in
      vascular medicine.
AB  - Contrast-enhanced ultrasound (CEUS) has emerged as a valuable imaging modality
      that complements and enhances standard vascular ultrasound imaging. Ultrasound
      contrast agents are gas-filled microbubbles that are injected intravenously and
      serve as intravascular tracers. Based on the properties to enhance and to
      quantify the macro- and microcirculation down to the capillary perfusion level in
      different vascular territories and organs, CEUS imaging has the potential to
      improve the diagnostic performance in the detection and characterisation of
      various vascular disorders reviewed in this article. In carotid atherosclerotic
      disease, CEUS imaging provides additional information on plaque vulnerability by
      illustrating the presence and extent of intraplaque neovascularisation. This new
      imaging modality may be helpful for further risk stratification of
      arteriosclerotic lesions and for detecting patients at risk for vascular events,
      eventually leading to more specific individually tailored therapeutic
      recommendations. CEUS imaging is also a helpful tool for the diagnosis and for
      monitoring of inflammatory vascular diseases. It increases the diagnostic
      performance of ultrasound in detecting inflammatory changes of the vessel wall
      such as hypervascularisation and hyperaemia. Changes in vessel wall enhancement
      may also reflect the response to anti-inflammatory therapy. Moreover, CEUS
      imaging is also a valuable tool for the assessment of the microcirculation and
      the tissue perfusion in solid organs including native and transplanted kidneys.
      The technique provides more accurate information on perfusion deficits of the
      parenchyma in patients with kidney infarction, necrosis or graft dysfunction.
      CEUS also has great potential in the assessment of the microcirculation of the
      skeletal muscle, particularly in patients with peripheral artery disease or
      diabetic microangiopathy. In the future, the use of targeted on site microbubbles
      could further enhance and expand the diagnostic capabilities of current vascular
      ultrasound by assessing specific molecular processes that play a role in the
      pathophysiology of vascular diseases. Furthermore, ultrasound-directed, site
      specific drug and gene delivery using microbubble contrast agents could gain
      great clinical value in the future. The combination of CEUS for diagnosis and
      therapy will provide unique opportunities for vascular clinicians to image the
      microcirculation and directly treat vascular diseases. 

PMID- 25588140
TI  - Guanidinium-rich, glycerol-derived oligocarbonates: a new class of cell
      penetrating molecular transporters that complex, deliver, and release siRNA.
AB  - A highly versatile and step-economical route to a new class of guanidinium-rich
      molecular transporters and evaluation of their ability to complex, deliver, and
      release siRNA are described. These new drug/probe delivery systems are prepared
      in only two steps, irrespective of length or composition, using an
      organocatalytic ring-opening co-oligomerization of glycerol-derived cyclic
      carbonate monomers incorporating either protected guanidine or lipid side chains.
      The resultant amphipathic co-oligomers are highly effective vehicles for siRNA
      delivery, providing an excellent level of target protein suppression (>85%).
      These new oligocarbonates are nontoxic at levels required for cell penetration
      and can be tuned for particle size. Relative to the previously reported
      methyl(trimethylene)carbonate (MTC) scaffold, the ether linkage at C2 in the new
      transporters markedly enhances the stability of the siRNA/co-oligomer complexes.
      Both hybrid co-oligomers, containing a mixture of glycerol- and MTC-derived
      monomers, and co-oligomers containing only glycerol monomers are found to provide
      tunable control over siRNA complex stability. On the basis of a glycerol and CO2
      backbone, these new co-oligomers represent a rapidly tunable and biocompatible
      siRNA delivery system that is highly effective in suppressing target protein
      synthesis. 

PMID- 25588142
TI  - Synthetic peptides reproducing tissue transglutaminase-gliadin complex neo
      epitopes as probes for antibody detection in celiac disease patients' sera.
AB  - Celiac disease (CD) patients usually present high levels of circulating IgA
      antibodies directed to different antigens, in particular tissue transglutaminase
      (tTG), gliadin (Glia), and endomysium. A series of synthetic peptide constructs
      containing cross-linked tTG and Glia deamidated peptides have been synthesized.
      Peptides were tested in enzyme-linked immunosorbent assays against celiac disease
      patients' sera versus normal blood donors, and their conformational features were
      evaluated by molecular modeling techniques. Four peptides were recognized as
      epitopes by autoantibodies (IgG class) circulating in CD patients' sera before
      gluten-free diet. The peptide II, containing Ac-tTG(553-564)-NH2 sequence cross
      linked with deamidated Ac-alpha2-Glia(63-71)-NH2, was able to identify specific
      disease antibodies with a sensitivity of 50% and a specificity of 94.4%.
      Structural conformations of the linear fragments Ac-tTG(553-564)-NH2 and Ac
      alpha2-Glia(63-71)-NH2 and the corresponding cross-linked peptide II were
      calculated by molecular modeling. Results showed that cross-linking is
      determinant to assume conformations, which are not accessible to the linear
      fragments.

PMID- 25588145
TI  - Determining pH at elevated pressure and temperature using in situ 13C NMR.
AB  - We have developed an approach for determining pH at elevated pressures and
      temperatures by using (13)C NMR measurements of inorganic carbon species together
      with a geochemical equilibrium model. The approach can determine in situ pH with
      precision better than 0.1 pH units at pressures, temperatures, and ionic
      strengths typical of geologic carbon sequestration systems. A custom-built high
      pressure NMR probe was used to collect (13)C NMR spectra of (13)C-labeled CO2
      reactions with NaOH solutions and Mg(OH)2 suspensions at pressures up to 107 bar
      and temperatures of 80  degrees C. The quantitative nature of NMR spectroscopy
      allows the concentration ratio [CO2]/[HCO3(-)] to be experimentally determined.
      This ratio is then used with equilibrium constants calculated for the specific
      pressure and temperature conditions and appropriate activity coefficients for the
      solutes to calculate the in situ pH. The experimentally determined [CO2]/[HCO3(
      )] ratios agree well with the predicted values for experiments performed with
      three different concentrations of NaOH and equilibration with multiple pressures
      of CO2. The approach was then applied to experiments with Mg(OH)2 slurries in
      which the change in pH could track the dissolution of CO2 into solution, rapid
      initial Mg(OH)2 dissolution, and onset of magnesium carbonate precipitation.

PMID- 25588144
TI  - Structural vulnerabilities to HIV/STI risk among female exotic dancers in
      Baltimore, Maryland.
AB  - Female exotic dancers (FEDs) are an important, yet understudied group of women
      who may engage in drug- and sex-related HIV/STI risk behaviors through their
      work. The study objective was to identify co-occurring indicators of
      vulnerability (e.g., housing, income, incarceration) associated with HIV/STI risk
      behavior among FEDs in Baltimore, Maryland. Surveys administered during July 2008
      February 2009 captured socio-demographic characteristics, drug use, and sexual
      practices among dancers (N = 101) aged >=18 years. Multivariate logistic
      regression was used to assess the relationship between vulnerability and risk
      behavior. Dancers with a high vulnerability score (i.e., 2 or more indicators)
      were more likely to report sex exchange (AOR: 10.7, 95% CIs: 2.9, 39.9) and
      multiple sex partnerships (AOR: 6.4, 95% CIs: 2.3, 18.3), controlling for
      demographics and drug use, compared to their less vulnerable counterparts.
      Findings point to primacy of macro-level factors that need to be addressed in
      HIV/STI prevention efforts targeting this and other high-risk populations. 

PMID- 25588146
TI  - Multiple orbital effects and magnetic ordering in a neutral radical.
AB  - The alternating ABABAB pi-stacked architecture of the EtCN solvate of the iodo
      substituted, oxobenzene-bridged bisdithiazolyl radical IBBO (space group Pnma)
      gives rise to strong ferromagnetic exchange along the pi-stacks, and the material
      orders as a spin-canted antiferromagnet with T(N) = 35 K, with a spontaneous
      (canted) moment M(spont) = 1.4 * 10(-3) MUB and a coercive field H(c) = 1060 Oe
      (at 2 K). The observation of spin-canting can only be understood in terms of
      multiorbital contributions to both isotropic and anisotropic exchange
      interactions, the magnitude of which are enhanced by spin-orbit effects arising
      from the heavy-atom iodine substituent. Pseudodipolar interactions lead to a net
      canted moment along the c-axis, while the sublattice magnetization is predicted
      to possess an easy a-axis.

PMID- 25588147
TI  - A Raman spectroscopic study of cell response to clinical doses of ionizing
      radiation.
AB  - The drive toward personalized radiation therapy (RT) has created significant
      interest in determining patient-specific tumor and normal tissue responses to
      radiation. Raman spectroscopy (RS) is a non-invasive and label-free technique
      that can detect radiation response through assessment of radiation-induced
      biochemical changes in tumor cells. In the current study, single-cell RS
      identified specific radiation-induced responses in four human epithelial tumor
      cell lines: lung (H460), breast (MCF-7, MDA-MB-231), and prostate (LNCaP),
      following exposure to clinical doses of radiation (2-10 Gy). At low radiation
      doses (2 Gy), H460 and MCF-7 cell lines showed an increase in glycogen-related
      spectral features, and the LNCaP cell line showed a membrane phospholipid-related
      radiation response. In these cell lines, only spectral information from
      populations receiving 10 Gy or less was required to identify radiation-related
      features using principal component analysis (PCA). In contrast, the MDA-MB-231
      cell line showed a significant increase in protein relative to nucleic acid and
      lipid spectral features at doses of 6 Gy or higher, and high-dose information
      (30, 50 Gy) was required for PCA to identify this biological response. The
      biochemical nature of the radiation-related changes occurring in cells exposed to
      clinical doses was found to segregate by status of p53 and radiation sensitivity.
      Furthermore, the utility of RS to identify a biological response in human tumor
      cells exposed to therapeutic doses of radiation was found to be governed by the
      extent of the biochemical changes induced by a radiation response and is
      therefore cell line specific. The results of this study demonstrate the utility
      and effectiveness of single-cell RS to identify and measure biological responses
      in tumor cells exposed to standard radiotherapy doses. 

PMID- 25588148
TI  - Antioxidant activity and mechanism of the abietane-type diterpene ferruginol.
AB  - The antioxidant activity of the abietane-type diterpene ferruginol was evaluated
      by comparison with that of carnosic acid, ( +/- )-alpha-tocopherol and
      dibutylhydroxytoluene using 2,2-diphenyl-1-picrylhydrazyl, beta-carotene
      bleaching and linoleic acid assays. Ferruginol had the lowest antioxidant
      activity of this group using the 2,2-diphenyl-1-picrylhydrazyl and beta-carotene
      methods in polar solvent buffer. However, ferruginol exhibited stronger activity
      than carnosic acid and alpha-tocopherol for linoleic acid oxidation under non
      solvent conditions. Five peaks corresponding to ferruginol derivatives were
      detected through GC-MS analysis of the reaction between ferruginol and methyl
      linoleate. The three reaction products were identified as dehydroferruginol,
      7beta-hydroxyferruginol and sugiol, and the other two peaks were assumed to be
      7alpha-hydroxyferruginol and the quinone methide derivative of ferruginol. The
      time course of the reaction suggests that the quinone methide was produced early
      in the reaction and reacted further to produce dehydroferruginol, 7
      hydroxyferruginol and sugiol. Thus, we inferred that quinone methide formation
      was a key step in the antioxidant reaction of ferruginol. 

PMID- 25588150
TI  - Are two hands sensing the load better than one?

PMID- 25588151
TI  - Enhancing ion yields in time-of-flight-secondary ion mass spectrometry: a
      comparative study of argon and water cluster primary beams.
AB  - Following from our previous Letter on this topic, this Article reports a detailed
      study of time-of-flight-secondary ion mass spectrometry (TOF-SIMS) positive ion
      spectra generated from a set of model biocompounds (arginine, trehalose, DPPC,
      and angiotensin II) by water cluster primary ion beams in comparison to argon
      cluster beams over a range of cluster sizes and energies. Sputter yield studies
      using argon and water beams on arginine and Irganox 1010 have confirmed that the
      sputter yields using water cluster beams lie on the same universal sputtering
      curve derived by Seah for argon cluster beams. Thus, increased ion yield using
      water cluster beams must arise from increased ionization. The spectra and
      positive ion signals observed using cluster beams in the size range from 1,000 to
      10,000 and the energy range 5-20 keV are reported. It is confirmed that water
      cluster beams enhance proton related ionization over against argon beams to a
      significant degree such that enhanced detection sensitivities from 1 MUm(2) in
      the region of 100 to 1,000 times relative to static SIMS analysis with Ar2000
      cluster beams appear to be accessible. These new studies show that there is an
      unexpected complexity in the ionization enhancement phenomenon. Whereas optimum
      ion yields under argon cluster bombardment occur in the region of E/n >= 10 eV
      (where E is the beam energy and n the number of argon atoms in the cluster) and
      fall rapidly when E/n < 10 eV; for water cluster beams, ion yields increase
      significantly in this E/n regime (where n is the number of water molecules in the
      cluster) and peak for 20 keV beams at a cluster size of 7,000 or E/n ~3 eV. This
      important result is explored further using D2O cluster beams that confirm that in
      this low E/n regime protonation does originate to a large extent from the water
      molecules. The results, encouraging in themselves, suggest that for both argon
      and water cluster beams, higher energy beams, e.g., 40 and 80 keV, would enable
      larger cluster sizes to be exploited with significant benefit for ion yield and
      hence analytical capability.

PMID- 25588149
TI  - c-Jun gene-modified Schwann cells: upregulating multiple neurotrophic factors and
      promoting neurite outgrowth.
AB  - Genetically modified Schwann cells (SCs) that overexpress neurotrophic factors
      (NFs), especially those that overexpress multiple NFs, hold great potential for
      promoting nerve regeneration. Currently, only one NF can be upregulated in most
      genetically modified SCs, and simultaneously upregulating multiple NFs in SCs
      remains challenging. In this study, we found that the overexpression of c-Jun, a
      component of the AP-1 transcription factor, effectively upregulated the
      expression and secretion of multiple NFs, including glial cell line-derived
      neurotrophic factor, brain-derived neurotrophic factor, artemin, leukemia
      inhibitory factor, and nerve growth factor. The c-Jun gene-modified SCs showed a
      normal morphology in scanning electron microscopy and fluorescent staining
      analysis. In addition, the c-Jun-modified SCs showed enhanced proliferation and
      migration abilities compared with vector control cells. We used transwell
      chambers to establish coculture systems imitating the in vivo conditions in which
      transplanted SCs might influence native SCs and neurons. We found that the c-Jun
      modified SCs enhanced native SC migration and promoted the proliferation of
      native SCs in the presence of axons. Further analysis revealed that in the c-Jun
      group, the average length and the total area of neurites divided by the total
      area of the explant body were MUm 1180+/-25 and 6.4+/-0.4, respectively, which
      were significantly greater compared with the other groups. These findings raise
      the possibility of constructing an optimal therapeutic alternative for nerve
      repair using c-Jun-modified SCs, which have the potential to promote axonal
      regeneration and functional recovery by upregulating multiple NFs. In addition,
      these cells exhibit enhanced migration and proliferation abilities, enhance the
      biological functions of native SCs, and promote neurite outgrowth. 

PMID- 25588152
TI  - BRAFV600E protein expression in primary cutaneous malignant melanomas and paired
      metastases.
AB  - IMPORTANCE: BRAFV600E mutations are present in approximately 50% of cutaneous
      malignant melanomas (CMMs). The use of BRAFV600E mutation-specific monoclonal
      antibody VE1 immunohistochemical analysis may facilitate rapid detection of
      BRAFV600E mutations in CMMs and demonstrate heterogeneity among tumors.
      OBJECTIVES: To characterize the pattern of BRAFV600E protein expression in
      primary CMMs with matched metastases and to analyze the use of VE1
      immunohistochemical analysis in clinical practice using formalin-fixed, paraffin
      embedded tumor tissue. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective
      cohort study performed at Karolinska University Hospital from September 2012 to
      September 2013, we examined CMMs (124 primary tumors and 76 metastases) with VE1
      immunohistochemical analysis, and results were compared with DNA mutation
      analyses. MAIN OUTCOMES AND MEASURES: Determination of intratumoral and
      intertumoral heterogeneity as well as the sensitivity and specificity of VE1
      immunohistochemical analysis. RESULTS: Positive staining results with the VE1
      antibody were detected in 94 of 200 tumors (47.0%). In general, VE1 staining was
      homogeneous. However, VE1 staining intensity varied among the primary tumors and
      corresponding metastases in 63 of 135 tumors (46.7%), but a change of mutational
      status based on DNA analysis was found in only 4 matched tumors (3.0%).
      Discordant findings between DNA mutation analysis and immunohistochemical
      analysis were observed in 12 tumors. The overall sensitivity and specificity of
      VE1 immunohistochemical analysis were 96.7% and 94.5%, respectively. A comparable
      sensitivity was obtained for primary and metastatic CMMs. The specificity was
      lower among primary CMMs (92.4%) compared with metastases (98.0%). CONCLUSIONS
      AND RELEVANCE: We found VE1 immunohistochemical analysis to be a useful and rapid
      assay for BRAFV600E mutations that may contribute to the detection of
      intratumoral and intertumoral heterogenetic subclones. Tumors with positive
      results, including strong staining, should be expedited for confirmatory BRAF
      mutation testing. If this test result is negative, a false-negative result of the
      mutation analysis should be considered. Validation of VE1 immunohistochemical
      analysis in clinical practice is needed.

PMID- 25588153
TI  - Depression CBT treatment gains among HIV-infected persons with a history of
      injection drug use varies as a function of baseline substance use.
AB  - Depression and substance use, the most common comorbidities with HIV, are both
      associated with poor treatment outcomes and accelerated HIV disease progression.
      Though previous research has demonstrated short-term and follow-up success for
      cognitive behavioral therapy for adherence and depression (CBT-AD) on depression
      outcomes among patients with HIV in care and among patients with HIV in active
      substance abuse treatment for injection drug use (IDU), there is little
      information regarding possible moderating effects of active use versus abstinence
      on depression treatment gains. The present study aimed to examine recent
      substance use at treatment initiation as a moderator of the acute and maintenance
      effects of CBT-AD on depression. We used data from a two-arm, randomized
      controlled trial (N = 89) comparing CBT-AD to enhanced treatment as usual in
      individuals in treatment for IDU. To test whether depression at time of
      presentation affected outcomes, repeated-measures ANOVAs were conducted for two
      time frames: (1) acute phase (baseline to post-treatment) (acute) and (2)
      maintenance phase (baseline to 12-month follow-up). To further examine
      maintenance of gains, we additionally looked at post-treatment to 12-month follow
      up. Depression scores derived from the clinical global impression for severity
      and the Montgomery-Asberg depression rating scale (MADRS) served as the primary
      outcome variables. Acute (baseline post treatment) moderation effects were found
      for those patients endorsing active drug use at baseline in the CBT-AD condition,
      who demonstrated the greatest reductions in MADRS scores at post-treatment
      (F[1,76] = 6.78, p = .01) and follow-up (F[1,61] = 5.46, p = .023). Baseline
      substance use did not moderate differences from post-treatment to 12-month follow
      up as depression treatment gains that occurred acutely from baseline to post
      treatment were maintained across both patients engaged in substance use and
      abstainers. We conclude that CBT-AD for triply diagnosed patients (i.e. HIV,
      depression, and substance dependence) is useful for treating depression for both
      patients with a history of substance use, as well as patients currently engaged
      in substance use.

PMID- 25588154
TI  - Health risk assessment for exposure to benzene in petroleum refinery
      environments.
AB  - The health risk resulting from benzene exposure in petroleum refineries was
      calculated using data from the scientific literature from various countries
      throughout the world. The exposure data was collated into four scenarios from
      petroleum refinery environments and plotted as cumulative probability
      distributions (CPD) plots. Health risk was evaluated for each scenario using the
      Hazard Quotient (HQ) at 50% (CEXP50) and 95% (CEXP95) exposure levels. Benzene
      levels were estimated to pose a significant risk with HQ50 > 1 and HQ95 > 1 for
      workers exposed to benzene as base estimates for petroleum refinery workers
      (Scenario 1), petroleum refinery workers evaluated with personal samplers in
      Bulgarian refineries (Scenario 2B) and evaluated using air inside petroleum
      refineries in Bulgarian refineries (Scenario 3B). HQ50 < 1 were calculated for
      petroleum refinery workers with personal samplers in Italian refineries (Scenario
      2A), air inside petroleum refineries (Scenario 3A) and air outside petroleum
      refineries (Scenario 4) in India and Taiwan indicating little possible adverse
      health effects. Also, HQ95 was < 1 for Scenario 4 however potential risk was
      evaluated for Scenarios 2A and 3A with HQ95 > 1. The excess Cancer risk (CR) for
      lifetime exposure to benzene for all the scenarios was evaluated using the Slope
      Factor and Overall Risk Probability (ORP) methods. The result suggests a
      potential cancer risk for exposure to benzene in all the scenarios. However,
      there is a higher cancer risk at 95% (CEXP95) for petroleum refinery workers (2B)
      with a CR of 48,000 per 106 and exposure to benzene in air inside petroleum
      refineries (3B) with a CR of 28,000 per 106. 

PMID- 25588155
TI  - Descriptive analysis of antibiotic-resistant patterns of methicillin-resistant
      Staphylococcus aureus (MRSA) st398 isolated from healthy swine.
AB  - BACKGROUND: Livestock-associated methicillin-resistant Staphylococcus aureus
      (MRSA) such as the MRSA ST398 strain has spread all over the world and the most
      worrying aspect of this fact appears to be its capacity to easily spread to
      humans. The excessive use of antibiotics has made swine a reservoir of MRSA. The
      aim of the present study was to determine the antibiotic resistance profile of
      MRSA samples isolated from healthy swine of the island of Tenerife (Spain).
      METHODS: A total of 256 MRSA isolates from swine samples and five MRSA isolates
      from pig worker samples were investigated for MRSA antibiotic resistant patterns.
      RESULTS: Analysis of the susceptibility status of MRSA pig isolates revealed that
      39 isolates were resistant to one antibiotic, 71 isolates were resistant to two
      antibiotics and 96 isolates were resistant to three or more antibiotics. SCCmec
      typing revealed the presence of types IV and V. Isolates having SCCmec IV had an
      increased resistance to the antimicrobial agents tested than those having SCCmec
      V. We observed significant differences when comparing the most common resistance
      patterns and SCCmec type. CONCLUSIONS: MRSA isolated from humans showed similar
      resistance to those isolated from pigs, excepting erythromycin, since all the
      workers' isolates were sensitive to this antibiotic. The evolution of new MRSA
      clones has emphasized the need for infection control practices in animals and
      humans in close contact.

PMID- 25588156
TI  - Public health adaptation to climate change in Canadian jurisdictions.
AB  - Climate change poses numerous risks to the health of Canadians. Extreme weather
      events, poor air quality, and food insecurity in northern regions are likely to
      increase along with the increasing incidence and range of infectious diseases. In
      this study we identify and characterize Canadian federal, provincial, territorial
      and municipal adaptation to these health risks based on publically available
      information. Federal health adaptation initiatives emphasize capacity building
      and gathering information to address general health, infectious disease and heat
      related risks. Provincial and territorial adaptation is varied. Quebec is a
      leader in climate change adaptation, having a notably higher number of adaptation
      initiatives reported, addressing almost all risks posed by climate change in the
      province, and having implemented various adaptation types. Meanwhile, all other
      Canadian provinces and territories are in the early stages of health adaptation.
      Based on publically available information, reported adaptation also varies
      greatly by municipality. The six sampled Canadian regional health authorities (or
      equivalent) are not reporting any adaptation initiatives. We also find little
      relationship between the number of initiatives reported in the six sampled
      municipalities and their provinces, suggesting that municipalities are adapting
      (or not adapting) autonomously. 

PMID- 25588157
TI  - Work related stress, burnout, job satisfaction and general health of nurses.
AB  - Gaps in research focusing on work related stress, burnout, job satisfaction and
      general health of nurses is evident within developing contexts like South Africa.
      This study identified the relationship between work related stress, burnout, job
      satisfaction and general health of nurses. A total of 1200 nurses from four
      hospitals were invited to participate in this cross-sectional study (75% response
      rate). Participants completed five questionnaires and multiple linear regression
      analysis was used to determine significant relationships between variables. Staff
      issues are best associated with burnout as well as job satisfaction. Burnout
      explained the highest amount of variance in mental health of nurses. These are
      known to compromise productivity and performance, as well as affect the quality
      of patient care. Issues, such as security risks in the workplace, affect job
      satisfaction and health of nurses. Although this is more salient to developing
      contexts it is important in developing strategies and intervention programs
      towards improving nurse and patient related outcomes. 

PMID- 25588158
TI  - Describing the primary care actions of oral health teams in Brazil.
AB  - OBJECTIVE: To describe the primary care actions performed by oral health teams
      (OHTs) that participated in a large national survey led by the Ministry of Health
      in 2012. METHODS: A total of 12,403 dentists from OHTs completed a set of survey
      questions (response rate = 85.01%) on the organization of care, basic dental
      procedures and oral health surveillance actions of OHTs. Descriptive and
      hierarchical cluster analyses were developed. RESULTS: The majority of OHTs
      (85.2%) reported that they performed "patient welcoming". The delivery of
      services was based on a patient's identified disease risk (83.1%), and continuity
      of care was ensured by 85.9% of OHTs. Individual preventive, restorative and
      surgical procedures were performed by the majority of the teams; however,
      screening for oral cancer and construction of dental prostheses/dentures occurred
      less frequently. Cluster 1 was composed of OHTs with the lowest proportion of
      oral healthcare actions related to oral cancer and dental prostheses/dentures,
      and the Southeastern and Southern regions had higher proportions of OHTs from
      cluster 2. CONCLUSIONS: OHTs adhere to some of the principles of primary care
      organizations; however, the teams perform fewer actions related to oral cancer
      treatment and rehabilitation with complete dentures. The geographical
      distribution of the clusters was unequal in Brazil.

PMID- 25588159
TI  - P-stereogenic PNP pincer-Pd catalyzed intramolecular hydroamination of amino-1,3
      dienes.
AB  - A new P-stereogenic PNP pincer-Pd complex was readily prepared from optically
      pure 2,6-bis[(boranato(tert-butyl)methylphosphino)methyl]pyridine. It was used in
      the asymmetric intramolecular hydroamination of amino-1,3-dienes, with the
      desired products being obtained in good yields and with excellent
      regioselectivities and up to moderate enantioselectivities. The absolute
      configuration of one of the hydroamination products was determined by X-ray
      crystallography studies. This simple and efficient procedure can be used for the
      synthesis of allyl-type chiral pyrrolidine derivatives. 

PMID- 25588160
TI  - Combination of SF1126 and gefitinib induces apoptosis of triple-negative breast
      cancer cells through the PI3K/AKT-mTOR pathway.
AB  - To investigate the apoptotic mechanism of triple-negative breast cancer (TNBC)
      cells induced by gefitinib and PI3K inhibitor SF1126. MDA-MB-231, MDA-MB-436, and
      MCF-7 cells were incubated with 0.1 MUmol/l gefitinib, 1 MUmol/l gefitinib, 10
      MUmol/l gefitinib, 1 MUmol/l SF1126, 0.1 MUmol/l gefitinib+1 MUmol/l SF1126, 1
      MUmol/l gefitinib+1 MUmol/l SF1126, and 10 MUmol/l gefitinib+1 MUmol/l SF1126.
      Then, cell viability and survival were determined using an 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst staining. The
      apoptosis-related factors and phosphoinositide-3-kinase/protein kinase B, the
      mammalian target of rapamycin (PI3K/AKT-mTOR) signaling pathway-related factors
      were detected by western blot. For TNBC cells, cell viability or survival was not
      significantly inhibited by gefitinib or SF1126 alone; however, marked cell
      apoptosis was noted in the gefitinib and SF1126 combination groups, and this
      effect was dose dependent. Also, the expressions of apoptosis markers, such as
      cleaved caspase-3, Bcl-2/Bax, were altered by the gefitinib and SF1126
      combination. Moreover, phosphorylated AKT (p-AKT) and 70 kDa ribosomal protein S6
      kinase (p-p70S6K) were also inhibited by the gefitinib and SF1126 combination,
      which may be responsible for the apoptosis. Gefitinib combined with SF1126 could
      induce cell apoptosis in TNBC cells and this effect was mediated through the EGFR
      PI3K-AKT-mTOR-p70S6K pathway. Our studies have set the stage for future clinical
      trials of TNBC therapy by the combination of gefitinib and SF1126. 

PMID- 25588161
TI  - N-Farnesyloxy-norcantharimide and N-farnesyl-norcantharimide inhibit the
      progression of leukemia and increase survival days in a syngeneic mouse leukemia
      model.
AB  - This study investigated the anticancer effects of two newly synthesized
      norcantharidin analogs, N-farnesyloxy-norcantharimide (NOC15) and N-farnesyl
      norcantharimide (NC15), in L1210 cells and in a syngeneic mouse leukemia model
      (L1210 cell line plus DBA/2 mice). We found that the half-maximal inhibitory
      concentration (IC50) of NOC15 and NC15 on L1210 cells is 1.56 and 2.62 MUmol/l,
      respectively, and that the IC50 of NOC15 and NC15 on human normal lymphoblast is
      207.9 and 2569 MUmol/l, respectively. In cell cycle analysis, NOC15 could
      increase the sub-G1 phase, whereas NC15 could induce G2/M arrest. Annexin-V
      apoptosis assay indicated that both NOC15 and NC15 could induce cell apoptosis.
      In the syngeneic mouse leukemia model, both NOC15 and NC15 could increase the
      survival days of mice and decrease the tumor weight. Moreover, both NOC15 and
      NC15 could retard the increase in peripheral blood leukocyte count due to L1210
      cells. In the subcutaneous (s.c.) group, the treatment with NOC15 could retard
      the decrease in the weight of the liver and the spleen caused by L1210 cells,
      whereas the treatment with NC15 could retard the decrease in the weight of the
      spleen caused by L1210 cells. We conclude that the new compounds NOC15 and NC15
      have strong anticancer activity and low toxicity both in vitro and in vivo. NOC15
      and NC15 may have the potential to be developed into anticancer agents in the
      future.

PMID- 25588162
TI  - The enhanced efficiency of graphene-silicon solar cells by electric field doping.
AB  - The graphene-silicon (Gr-Si) Schottky junction solar cell has been recognized as
      one of the most low-cost candidates in photovoltaics due to its simple
      fabrication process. However, the low Gr-Si Schottky barrier height largely
      limits the power conversion efficiency of Gr-Si solar cells. Here, we demonstrate
      that electric field doping can be used to tune the work function of a Gr film and
      therefore improve the photovoltaic performance of the Gr-Si solar cell
      effectively. The electric field doping effects can be achieved either by
      connecting the Gr-Si solar cell to an external power supply or by polarizing a
      ferroelectric polymer layer integrated in the Gr-Si solar cell. Exploration of
      both of the device architecture designs showed that the power conversion
      efficiency of Gr-Si solar cells is more than twice of the control Gr-Si solar
      cells. Our study opens a new avenue for improving the performance of Gr-Si solar
      cells. 

PMID- 25588163
TI  - Swept source optical coherence tomography Gabor fusion splicing technique for
      microscopy of thick samples using a deformable mirror.
AB  - We present a swept source optical coherence tomography (OCT) system at 1060 nm
      equipped with a wavefront sensor at 830 nm and a deformable mirror in a closed
      loop adaptive optics (AO) system. Due to the AO correction, the confocal profile
      of the interface optics becomes narrower than the OCT axial range, restricting
      the part of the B-scan (cross section) with good contrast. By actuating on the
      deformable mirror, the depth of the focus is changed and the system is used to
      demonstrate Gabor filtering in order to produce B-scan OCT images with enhanced
      sensitivity throughout the axial range from a Drosophila larvae. The focus
      adjustment is achieved by manipulating the curvature of the deformable mirror
      between two user-defined limits. Particularities of controlling the focus for
      Gabor filtering using the deformable mirror are presented.

PMID- 25588164
TI  - Optical palpation in vivo: imaging human skin lesions using mechanical contrast.
AB  - We demonstrate the first application of the recently proposed method of optical
      palpation to in vivo imaging of human skin. Optical palpation is a tactile
      imaging technique that probes the spatial variation of a sample's mechanical
      properties by producing an en face map of stress measured at the sample surface.
      This map is determined from the thickness of a translucent, compliant stress
      sensor placed between a loading element and the sample and is measured using
      optical coherence tomography. We assess the performance of optical palpation
      using a handheld imaging probe on skin-mimicking phantoms, and demonstrate its
      use on human skin lesions. Our results demonstrate the capacity of optical
      palpation to delineate the boundaries of lesions and to map the mechanical
      contrast between lesions and the surrounding normal skin.

PMID- 25588165
TI  - Optical diagnosis of malaria infection in human plasma using Raman spectroscopy.
AB  - We present the prediction of malaria infection in human plasma using Raman
      spectroscopy. Raman spectra of malaria-infected samples are compared with those
      of healthy and dengue virus infected ones for disease recognition. Raman spectra
      were acquired using a laser at 532 nm as an excitation source and 10 distinct
      spectral signatures that statistically differentiated malaria from healthy and
      dengue-infected cases were found. A multivariate regression model has been
      developed that utilized Raman spectra of 20 malaria-infected, 10 non-malarial
      with fever, 10 healthy, and 6 dengue-infected samples to optically predict the
      malaria infection. The model yields the correlation coefficient r(2) value of
      0.981 between the predicted values and clinically known results of trainee
      samples, and the root mean square error in cross validation was found to be 0.09;
      both these parameters validated the model. The model was further blindly tested
      for 30 unknown suspected samples and found to be 86% accurate compared with the
      clinical results, with the inaccuracy due to three samples which were predicted
      in the gray region. Standard deviation and root mean square error in prediction
      for unknown samples were found to be 0.150 and 0.149, which are accepted for the
      clinical validation of the model.

PMID- 25588166
TI  - Cement-associated signs of inflammation: retrospective analysis of the effect of
      excess cement on peri-implant tissue.
AB  - PURPOSE: Excess cement left in the peri-implant sulcus after the placement of
      prosthetic restorations risks inflammation in the peri-implant tissue. While many
      current studies deal with the question of how to avoid undetected excess cement,
      relatively little is known about the clinical consequences of this complication.
      This study analyzed the clinical findings associated with excess cement. Further,
      the influence of the sojourn time of undetected excess cement in the peri-implant
      pocket on clinical findings was investigated. MATERIALS AND METHODS: Within the
      scope of a retrospective clinical follow-up, the suprastructures that were
      originally cemented with a methacrylate cement were revised in 93 patients (171
      implants). The patients were split into two groups according to the time between
      placement of the prosthetic restoration and revision. Group 1 (G1) had treatment
      revisions within 2 years of restoration placement (71 patients with 126
      implants); in group 2 (G2), treatment revisions were conducted at a later time
      (22 patients with 45 implants). For the purpose of statistical analysis, both
      groups were further analyzed based on the presence/absence of excess cement at
      the time of revision. RESULTS: By definition, the average time to revision in G1
      was shorter than in G2 (0.71 years versus 4.07 years). There was no significant
      difference in the frequency of excess cement at revision between G1 (59.5%) and
      G2 (62.2%). The clinical findings around the implants in G1 were significantly
      less severe than in G2 (bleeding on probing: G1 without excess cement--17.6%, G1
      with excess cement--80%, G2 without excess cement--94.1%, G2 with excess cement-
      100%; suppuration: G1 without excess--0%, G1 with excess cement--21.3%, G2
      without excess cement--23.3%, G2 with excess cement--89.3%). After removing the
      excess cement, cleaning and disinfecting the implant abutment and restoration,
      and using a different cement, significantly fewer signs of inflammation were
      found at further follow-up in both groups. CONCLUSIONS: Within the limitations of
      this retrospective observational study, excess cement was present in a high
      number of cement-retained implant restorations. Signs of inflammation were
      present in a large proportion of implants at short- to medium-term follow-up. At
      the time of restoration revisions, the clinical observation of previously
      undetected excess cement was associated with increased prevalence of
      inflammation. Removal of excess cement significantly reduced the signs of
      inflammation.

PMID- 25588167
TI  - The influence of interimplant distance in mandibular overdentures supported by
      two implants on patient satisfaction and quality of life.
AB  - This study evaluates the influence of interimplant distance (ID) on patient
      satisfaction and quality of life (QOL) of 55 patients who received mandibular
      overdentures supported by two implants. IDs were measured over the residual ridge
      crest and linearly on all of the patients' mandibular casts. The crestal detours
      of all patients were determined by subtracting these two values from each other.
      Higher IDs were associated with better QOL scores (P < .05), whereas higher
      crestal detour values were associated with better general comfort, chewing, ease
      of hygiene maintenance, esthetics, pain, and QOL scores (P < .05). 

PMID- 25588168
TI  - Retrievability of implant-supported crowns when using three different cements: a
      controlled clinical trial.
AB  - PURPOSE: The purpose of this study was to analyze the removal of implant
      supported crowns retained by three different cements using an air-accelerated
      crown remover and to evaluate the patients' response to the procedure. MATERIALS
      AND METHODS: This controlled clinical trial was conducted with 21 patients (10
      women, 11 men; mean age: 51 +/- 10.2 years) who had received a total of 74
      implants (all placed in the posterior zone of the mandible). Four months after
      implant surgery, the crowns were cemented on standard titanium abutments of
      different heights. Three different cements (two temporary: Harvard TEMP and
      Improv; and one definitive: Durelon) were used and randomly assigned to the
      patients. Eight months later, one blinded investigator removed all crowns. The
      number of activations of the instrument (CORONAflex, KaVo) required for crown
      removal was recorded. The patients completed a questionnaire retrospectively to
      determine the impact of the procedure and to gauge their subjective perception. A
      linear regression model and descriptive statistics were used for data analysis.
      RESULTS: All crowns could be retrieved without any technical complications or
      damage. Both abutment height (P = .019) and cement type (P = .004) had a
      significant effect on the number of activations, but the type of cement was more
      important. An increased total number of activations had no or only a weak
      correlation to the patients' perception of concussion, noise, pain, and
      unwillingness to use the device. CONCLUSIONS: Cemented implant crowns can be
      removed, and the application of an air-accelerated device is a practicable
      method. A type of cement with appropriate retention force has to be selected. The
      impact on the patients' subjective perception should be taken into account.

PMID- 25588169
TI  - Randomized controlled trial comparing direct intraoral digitization and extraoral
      digitization after impression taking.
AB  - This study aimed to evaluate the correspondence of intraoral digitization (ID)
      with extraoral digitization (ED) after impression taking. One-stage putty-and
      wash impressions and ID were carried out in a randomized order for 10 subjects.
      The impressions were used to make casts, which were then subjected to ED. ID
      datasets were aligned to create computer-aided design reference models.
      Deviations between ID and ED were calculated. The mean positive and negative
      deviations were 37.7 and -48.4 um, respectively, for one quadrant. The results
      showed that the ID system is well suited for the acquisition of single-tooth
      restorations and is of limited suitability for the acquisition of small multiple
      unit restorations. 

PMID- 25588170
TI  - Fixed full-arch implant-supported prostheses in a patient with epidermolysis
      bullosa: a clinical case history report.
AB  - Epidermolysis bullosa (EB) is a rare skin disorder characterized by blister
      formation in response to minor trauma and accompanied by extracutaneous
      manifestations. The use of endosseous implants to support fixed prostheses for
      the rehabilitation of patients with recessive dystrophic EB might provide a
      considerably better clinical treatment outcome than traditional prosthodontic
      interventions. This case history report describes the clinical management of such
      an afflicted patient. Implants were placed immediately following teeth
      extractions and subsequently loaded with fixed full-arch prostheses. This
      treatment option is proposed for patients with recessive dystrophic EB to
      preclude mucosal irritation associated with wearing removable prostheses. 

PMID- 25588171
TI  - Adhesive strength of the luting technique for passively fitting screw-retained
      implant-supported prostheses: an in vitro evaluation.
AB  - PURPOSE: This in vitro study evaluated the adhesive strength of a technique to
      lute implant cylinders to metal frameworks in implant-supported prostheses and
      ensure a good passive fit. MATERIALS AND METHODS: Different height samples were
      tested: In group 1, implant cylinders were 5 mm long; in group 2, they were 10 mm
      long. A universal testing machine (Instron) was used to perform pullout tests.
      RESULTS: The luting technique provided enough adhesive strength for clinical use
      with greater adhesive strength in group 2 (mean pull-out strength: 2.85 kN in
      group 1 versus 3.79 kN in group 2). CONCLUSIONS: The luting technique provides
      enough adhesive strength for clinical use. Moreover, specimens with a larger
      surface for adhesion demonstrated higher adhesive strength compared with shorter
      specimens.

PMID- 25588172
TI  - The effect of implant design and bone quality on insertion torque, resonance
      frequency analysis, and insertion energy during implant placement in low or low-
      to medium-density bone.
AB  - PURPOSE: This study investigated the effect of implant design and bone quality on
      insertion torque (IT), implant stability quotient (ISQ), and insertion energy
      (IE) by monitoring the continuous change in IT and ISQ while implants were
      inserted in artificial bone blocks that simulate bone of poor or poor-to-medium
      quality. MATERIALS AND METHODS: Polyurethane foam blocks (Sawbones) of 0.16 g/cm3
      and 0.32 g/cm3 were respectively used to simulate low density and low- to medium
      density cancellous bone. In addition, some test blocks were laminated with a 1-mm
      0.80 g/cm3 polyurethane layer to simulate cancellous bone with a thin cortical
      layer. Four different implants (Nobel Biocare Mk III-3.75, Mk III-4.0, Mk IV-4.0,
      and NobelActive-4.3) were placed into the different test blocks in accordance
      with the manufacturer's instructions. The IT and ISQ were recorded at every 0.5
      mm of inserted length during implant insertion, and IE was calculated from the
      torque curve. The peak IT (PIT), final IT (FIT), IE, and final ISQ values were
      statistically analyzed. RESULTS: All implants showed increasing ISQ values when
      the implant was inserted more deeply. In contrast to the ISQ, implants with
      different designs showed dissimilar IT curve patterns during the insertion. All
      implants showed a significant increase in the PIT, FIT, IE, and ISQ when the test
      block density increased or when the 1-mm laminated layer was present. Tapered
      implants showed FIT or PIT values of more than 40 Ncm for all of the laminated
      test blocks and for the nonlaminated test blocks of low to medium density.
      Parallel-wall implants did not exhibit PIT or FIT values of more than 40 Ncm for
      all of the test blocks. NobelActive-4.3 showed a significantly higher FIT, but a
      significantly lower IE, than Mk IV-4.0. CONCLUSIONS: While the existence of
      cortical bone or implant designs significantly affects the dynamic IT profiles
      during implant insertion, it does not affect the ISQ to a similar extent. Certain
      implant designs are more suitable than others if high IT is required in bone of
      poor quality. The manner in which IT, IE, and ISQ represent the implant primary
      stability requires further study.

PMID- 25588173
TI  - Simplified edentulous treatment technique for edentulous hemimaxillectomy
      patients: case history report.
AB  - Technical difficulties in the construction of hard palate obturators following
      oncologic surgery are due to the recording limitations of the entire defect area,
      plus prosthesis base instability during recording of maxillomandibular
      relationships. This article describes a time-saving technique that ensures stable
      and precise recording bases. A light-polymerizing acrylic resin layer is used for
      making the first impression of the defect, while simultaneously obtaining an
      acrylic resin impression tray and base for recording maxillomandibular
      relationships. Adhesive paper copies are used for the arrangement of the anterior
      teeth. 

PMID- 25588174
TI  - Systematic review of current dental implant coating materials and novel coating
      techniques.
AB  - PURPOSE: Titanium dental implants have a high success rate; however, there are
      instances when a modified surface may be desirable. The aim of this article was
      to systematically review the different types of implant coatings that have been
      studied clinically, in vivo and in vitro, and the coating techniques being
      implemented. MATERIALS AND METHODS: The literature was searched electronically
      and manually through The Cochrane Library, Medline, and PubMed databases to
      identify articles studying dental implant surfaces and coating techniques. The
      database search strategy revealed 320 articles, of which 52 articles were
      considered eligible--40 in relation to implant coatings and 12 to the coating
      technique. An additional 30 articles were retrieved by hand search. RESULTS:
      Several materials were identified as possible candidates for dental implant
      coatings; these include carbon, bisphosphonates, bone stimulating factors,
      bioactive glass and bioactive ceramics, fluoride, hydroxyapatite (HA) and calcium
      phosphate, and titanium/titanium nitride. HA coatings still remain the most
      biocompatible coatings even though the more innovative bioglass suggests
      promising results. The most common coating techniques are plasma spraying and
      hydrocoating. More recent techniques such as the nanoscale technology are also
      discussed. CONCLUSIONS: Several implant coatings have been proposed, and some
      appear to give better clinical results and improved properties than others.
      Clinical trials are still required to provide compelling evidence-based results
      for their long-term successful outcomes.

PMID- 25588175
TI  - Perception of dental esthetics: influence of restoration type, symmetry, and
      color in four different countries.
AB  - In this study, the influence of restoration type, symmetry, and color on the
      perception of dental appearance was evaluated. An esthetic questionnaire was
      completed by 29 patients before and after esthetic rehabilitation. In addition,
      94 dentists from four countries (Germany, the United Kingdom [UK], China, and
      Switzerland) evaluated the influence of the above factors using before-and-after
      rehabilitation pictures. The most invasive treatment was recommended by Chinese
      dentists, while German, Swiss, and UK dentists recommended comparable treatment
      options. As for restorative symmetry, restoration type, and color, significant
      differences could be found among and within the dentists of the four countries (P
      +/- .05). 

PMID- 25588176
TI  - In situ evaluation of the microbial adhesion on a hard acrylic resin and a soft
      liner used in removable prostheses.
AB  - PURPOSE: The purpose of this study was to evaluate, in situ, the initial adhesion
      of microorganisms to as well as the surface roughness and chemical composition of
      ProBase Hot (Ivoclar Vivadent), a hard acrylic resin, and Vertex Soft (Vertex
      Dental), an acrylic-based soft liner, used in removable dental prostheses.
      MATERIALS AND METHODS: Equal sized disks of ProBase Hot and Vertex Soft were
      prepared and polished according to the recommended procedures for clinical use.
      Two disks of each material were mounted in individual oral splints and exposed
      for 4 hours to the oral cavities of 15 participants. The microbial adhesion to
      each material's surface was measured with the pour plate technique using rich and
      selective growth media. Statistical analysis was performed using the Student t
      test. Scanning electron microscopy and chemical composition analyses obtained
      through electron probe radiographic microanalysis of sample disks also were
      performed. RESULTS: In comparison to ProBase Hot, Vertex Soft presented higher
      microbial adhesion, namely regarding total aerobes, anaerobes, streptococci, and
      mutans streptococci (P < .05). Also, Vertex Soft presented higher surface
      roughness. Differences in the chemical composition of the two materials also were
      found. CONCLUSIONS: The Vertex Soft liner has been found to be more susceptible
      to microbial adhesion than the acrylic resin ProBase Hot, probably due to its
      greater surface roughness. The application of Vertex Soft liner to a hard denture
      base may lead to a higher risk of oral and systemic infections for patients,
      highlighting a greater need for plaque control, especially for more susceptible
      individuals.

PMID- 25588177
TI  - Hormonal fluctuations intensify temporomandibular disorder pain without impairing
      masticatory function.
AB  - PURPOSE: The influence of hormonal fluctuations on pain and mastication was
      evaluated in patients with painful temporomandibular disorder (TMD) symptoms.
      MATERIALS AND METHODS: Fifty women were assigned to menstrual cycle and oral
      contraceptive groups (n = 25). Their TMD was diagnosed by Research Diagnostic
      Criteria for Temporomandibular Disorders. Pain levels, maximum oclusal force
      (MOF), and masticatory performance (MP) were measured in all menstrual cycle
      phases. RESULTS: A lower pain level was observed in the ovulatory phase when
      compared to menstrual and luteal phases (P = .02). No differences were found
      regarding MOF (P = .20) or MP (P = .94). CONCLUSIONS: Hormonal fluctuations
      intensify pain in women with symptomatic TMD without impairing mastication.

PMID- 25588178
TI  - Reliability and failure modes of two Y-TZP abutment designs.
AB  - Fracture strength and accelerated fatigue reliability of two zirconia abutment
      systems were tested. Thirty-six implants with a Morse taper (MT; n = 18) or cone
      (C; n = 18) design were restored with metallic crowns. Loads were applied as
      single load to failure (SLF) or mouth-motion cycles using a step-stress
      accelerated life testing (SALT) method. SLF mean values were 690 +/- 430 N and
      209 +/- 25 for MT and C groups, respectively. In terms of the SALT results, 8
      specimens survived (50,000 cycles) and 7 failed (maximum load 400 N) in the MT
      group; whereas for the C group all abutments failed before the maximum number of
      cycles. Failure mode was fracture of the Y-TZP abutments for both groups. Higher
      reliability for a mission of 50,000 cycles at 175 N for MT versus C designs was
      determined, and significant differences in fracture modes were observed. 

PMID- 25588179
TI  - Electromyographic evaluation of masticatory muscles in dentate patients versus
      conventional and implant-supported fixed and removable denture wearers- a
      preliminary report comparing model foods.
AB  - PURPOSE: To evaluate differences in masticatory muscle function during chewing of
      model foods designed to differ in fracture strength between dentate subjects (n =
      5, ages 59 to 68 years) versus patients treated with a maxillary conventional
      complete denture opposing natural dentition or one of the following types of
      mandibular complete dentures: conventional, implant-supported overdenture,
      implant-supported fixed denture (n = 20, ages 45 to 83 years). The authors
      hypothesized that denture wearers would differ in duration of chewing, frequency
      of chewing, and masticatory muscle activity while preparing a bolus for
      swallowing. MATERIALS AND METHODS: Surface electromyography was recorded
      bilaterally from the masseter, anterior temporalis, and anterior digastric.
      Masticatory muscle activity was evaluated using scaled values of the area under
      the electromyographic curve, while subjects chewed agar-based model foods with
      different fracture strengths. Chewing duration and frequency also were calculated
      from electromyographic recordings. Mixed model analysis of variance with
      "subject" as a random factor was used during statistical analysis. Logarithmic
      transformation was required to achieve normalization of residuals for the
      duration of chewing and the relative masticatory muscles activity, but not for
      the chewing frequency. RESULTS: Relative masticatory muscle activity was 2.57
      times higher for the denture wearers than for the dentate subjects during chewing
      of model foods (P < .0001). The reduction in masticatory muscle activity from the
      1st to the 10th chewing cycle was proportionally less in magnitude and occurred
      more gradually for denture wearers compared to dentate subjects. While chewing
      sequence duration increased with food fracture strength, it did not differ
      significantly in treatment versus dentate groups. Chewing cycle frequency did not
      differ between groups or with food fracture strength. CONCLUSIONS: The observed
      increases in relative masticatory muscle activity for denture wearers compared to
      the dentate subjects during oral food processing likely reflect supplemental
      mechanical efforts to accommodate the use of dentures for preparing a bolus for
      swallowing.

PMID- 25588180
TI  - Highly active and stable hybrid catalyst of cobalt-doped FeS2 nanosheets-carbon
      nanotubes for hydrogen evolution reaction.
AB  - Hydrogen evolution reaction (HER) from water through electrocatalysis using cost
      effective materials to replace precious Pt catalysts holds great promise for
      clean energy technologies. In this work we developed a highly active and stable
      catalyst containing Co doped earth abundant iron pyrite FeS(2) nanosheets
      hybridized with carbon nanotubes (Fe(1-x)CoxS(2)/CNT hybrid catalysts) for HER in
      acidic solutions. The pyrite phase of Fe(1-x)CoxS(2)/CNT was characterized by
      powder X-ray diffraction and absorption spectroscopy. Electrochemical
      measurements showed a low overpotential of ~0.12 V at 20 mA/cm(2), small Tafel
      slope of ~46 mV/decade, and long-term durability over 40 h of HER operation using
      bulk quantities of Fe(0.9)Co(0.1)S(2)/CNT hybrid catalysts at high loadings (~7
      mg/cm(2)). Density functional theory calculation revealed that the origin of high
      catalytic activity stemmed from a large reduction of the kinetic energy barrier
      of H atom adsorption on FeS(2) surface upon Co doping in the iron pyrite
      structure. It is also found that the high HER catalytic activity of
      Fe(0.9)Co(0.1)S(2) hinges on the hybridization with CNTs to impart strong
      heteroatomic interactions between CNT and Fe(0.9)Co(0.1)S(2). This work produces
      the most active HER catalyst based on iron pyrite, suggesting a scalable, low
      cost, and highly efficient catalyst for hydrogen generation.

PMID- 25588181
TI  - Chemical and toxicological characterization of halobenzoquinones, an emerging
      class of disinfection byproducts.
AB  - Halobenzoquinones (HBQs), a new class of disinfection byproducts (DBPs), occur
      widely in treated drinking water and recreational water. The main concern
      regarding human exposure to DBPs stems from epidemiological studies that have
      consistently linked the consumption of chlorinated drinking water with an
      increased risk of developing bladder cancer. The U.S. Environmental Protection
      Agency and Health Canada have set regulations on the amount of DBPs in drinking
      water to minimize the risk. However, these regulated DBPs do not account for the
      increased risk of bladder cancer because they have different target organs or
      lower magnitudes of risk based on animal carcinogenesis studies. Because of the
      pervasive exposure to DBPs, identification of DBPs relevant to human health has
      become one of the important research targets to address DBP-associated health
      concerns. Quantitative structure-toxicity relationship (QSTR) analysis has
      predicted HBQs to be potential bladder carcinogens. Therefore, this perspective
      focuses on the chemical and toxicological characterization of HBQs. In vitro
      cytotoxicity experiments have shown that HBQs induce greater cytotoxicity and/or
      greater developmental toxicity than most of the regulated DBPs. Cellular
      mechanistic studies indicate that HBQs are capable of producing reactive oxygen
      species (ROS) either within cells or in solution, depleting cellular glutathione
      levels, and influencing cellular antioxidant enzymes, which further induces
      oxidative stress and oxidative damage to cellular proteins and DNA. Oxidative
      damage to DNA was demonstrated in the form of significant increases in cellular
      levels of 8-hydroxydeoxyguanosine (8-OHdG), DNA strand breaks, and
      apurinic/apyrimidinic (AP) sites. HBQs can also form DNA adducts, affect genome
      wide DNA methylation, and inhibit DNA repair enzymes. These findings demonstrate
      that HBQs are highly cytotoxic and potentially genotoxic and carcinogenic,
      although in vivo data corroborating this is not available. To fully understand
      the potential adverse health effects and cancer risk due to HBQ exposure,
      multidisciplinary research is required regarding human exposure, health risk
      assessment, and toxicological mechanisms of HBQs. 

PMID- 25588182
TI  - Capturing heterogeneous nucleation of nanoscale pits and subsequent crystal
      shrinkage during Ostwald ripening of a metal phosphate.
AB  - It has been generally accepted that crystal shrinkage during Ostwald ripening can
      be understood simply as a reverse process of crystal growth, and as a result,
      little attention has been paid to shrinkage behavior. The entire microstructure
      of polycrystalline materials, however, forms as a consequence of both growing and
      shrinking crystals. Thus, scrutiny of shrinking characteristics in addition to
      growth aspects is essential for a complete understanding of the evolution of
      microstructure during Ostwald ripening. By capturing real-time in situ high
      resolution electron micrographs at high temperature, we herein demonstrate the
      shrinkage behavior of nanocrystals embedded in a solid crystalline matrix during
      the ripening process of a metal phosphate. Unlike typical crystal growth behavior
      based on two-dimensional homogeneous nucleation, heterogeneous types of
      nucleation with nanoscale pits at solid-solid interfaces (or crystal edges) are
      observed to dominantly occur during shrinkage of the crystals. The findings of
      this study suggest that crystal shrinkage proceeds with a lower activation energy
      barrier than that of crystal growth, although both crystal growth and shrinkage
      take place at the same time during Ostwald ripening. 

PMID- 25588184
TI  - "When I'm rushing on my run" - novel psychoactive substances.

PMID- 25588183
TI  - A checklist-based intervention to improve surgical outcomes in Michigan:
      evaluation of the Keystone Surgery program.
AB  - IMPORTANCE: Previous studies of checklist-based quality improvement interventions
      have reported mixed results. OBJECTIVE: To evaluate whether implementation of a
      checklist-based quality improvement intervention--Keystone Surgery--was
      associated with improved outcomes in patients in a large statewide population
      undergoing general surgery. DESIGN, SETTING, AND EXPOSURES: A retrospective
      longitudinal study examined surgical outcomes in 64,891 Michigan patients in 29
      hospitals using Michigan Surgical Quality Collaborative clinical registry data
      from 2006 through 2010. Multivariable logistic regression and difference-in
      differences analytic approaches were used to evaluate whether Keystone Surgery
      program implementation was associated with improved surgical outcomes following
      general surgery procedures, apart from existing temporal trends toward improved
      outcomes during the study period. MAIN OUTCOMES AND MEASURES: Risk-adjusted rates
      of superficial surgical site infection, wound complication, any complication, and
      30-day mortality. RESULTS: Implementation of Keystone Surgery in 14 participating
      centers was not associated with improvements in surgical outcomes during the
      study period. Adjusted rates of superficial surgical site infection (3.2% vs
      3.2%, P=.91), wound complication (5.9% vs 6.5%, P=.30), any complication (12.4%
      vs 13.2%, P=.26), and 30-day mortality (2.1% vs 1.9%, P=.32) at participating
      hospitals were similar before and after implementation. Difference-in-differences
      analysis accounting for trends in 15 nonparticipating centers and sensitivity
      analysis excluding patients receiving surgery in the first 6 or 12 months after
      program implementation yielded similar results. CONCLUSIONS AND RELEVANCE:
      Implementation of a checklist-based quality improvement intervention did not
      affect rates of adverse surgical outcomes among patients undergoing general
      surgery in participating Michigan hospitals. Additional research is needed to
      understand why this program was not successful prior to further dissemination and
      implementation of this model to other populations.

PMID- 25588186
TI  - The In vitro and In vivo Evaluation of Fenofibrate with a Self-microemulsifying
      Formulation.
AB  - Fenofibrate is virtually insoluble in water and is highly lipophilic, which leads
      to poor oral bioavailability. The purpose of this approach is to develop self
      microemulsifying drug delivery system (SMEDDS) for oral bioavailability
      enhancement of fenofibrate. The in vitro dissolution test and pharmacokinetic
      behavior in beagle dogs were conducted to assess the formulation of fenofibrate
      in self-microemulsifying systems. The concentrations of fenofibrate were
      determined by HPLC. A crossover fashion study was performed in six fasted beagle
      dogs with SMEDDS formulation and commercial capsules. The results showed that
      SMEDDS formulation provide a good drug release with more than 90% of fenofibrate
      dissoluted from self-emulsifying formulations while less than 10% from the
      commercial capsules was released within 20min. The mean particle size of SMEDDS
      formulation after dispersion was about 33.7nm In pharmacokinetic parameters of
      SMEDDS formulation, the area under the plasma concentration-time curve (AUC) was
      significantly higher and was approximately 7-fold greater than that obtained when
      commercial capsule of the same dose of fenofibrate was administered. Also, the
      maximum absorption was advanced (2h to 1.25h) with SMEDDS formulation. The self
      microemulsifying drug delivery systems can significantly increase fenofibrate
      dissolution in vitro and absorption in vivo.

PMID- 25588185
TI  - [S3-Guideline: Recommendations for intra-aortic balloon pumping in cardiac
      surgery].
AB  - Although intra-aortic balloon pumping (IABP) is the most frequently used
      mechanical cardiac assist device in cardiothoracic surgery, there are only
      guidelines for substantive sections of aortic counterpulsation including
      prophylactic and postoperative use. In contrast, evidence-based recommendations
      are still lacking concerning intraoperative use, management, contraindication and
      other relevant issues. According to international surveys, important aspects of
      IABP usage show a wide variation in clinical practice. The results of a national
      questionnaire performed before initiation of this guideline confirmed these
      findings and demonstrated a clear need for the development of a consensus-based
      guideline. Therefore, the presented multidisciplinary S-3-guideline was developed
      under the direction of the German Society for Thoracic and Cardiovascular Surgery
      (Deutsche Gesellschaft fur Thorax-, Herz- und Gefabetachirurgie, DGTHG) to make
      evidence-based recommendations for the usage of aortic counterpulsation after
      cardiothoracic surgery according to the requirements of the Association of the
      Scientific Medical Societies in Germany (AWMF) and the Medical Centre for Quality
      (Arztliches Zentrum fur Qualitat - (AZQ)). Main topics discussed in this
      guideline involve IABP support in the prophylactic, preoperative, intraoperative
      and postoperative setting as well as the treatment of right heart failure,
      contraindications, anticoagulation, monitoring, weaning, and limitations of IABP
      therapy. The presented 15 key messages of the guideline were approved after two
      consensus meetings under moderation of the AWMF with participation of the German
      Society of Cardiology (DGK), German Society of Anaesthesiology and Intensive Care
      Medicine (DGAI), German Interdisciplinary Association for Intensive Care (DIVI)
      and the German Society for Cardiovascular Engineering (DGfK).

PMID- 25588187
TI  - Stabilizing electrochemical carbon capture membrane with Al2O3 thin-film
      overcoating synthesized by chemical vapor deposition.
AB  - Development of high-efficiency and cost-effective carbon capture technology is a
      central element of our effort to battle the global warming and climate change.
      Here we report that the unique high-flux and high-selectivity of electrochemical
      silver-carbonate dual-phase membranes can be retained for an extended period of
      operation by overcoating the surfaces of porous silver matrix with a uniform
      layer of Al2O3 thin-film derived from chemical vapor deposition. 

PMID- 25588188
TI  - Nonsevere acute pulmonary embolism: prognostic CT pulmonary angiography findings.
AB  - PURPOSE: To retrospectively evaluate the prognostic parameters of computed
      tomography (CT) pulmonary angiographic findings in nonsevere (hemodynamically
      stable) pulmonary embolism (PE) patients and to assess the predictive value of
      these parameters for mortality within 1 month of the initial diagnosis. MATERIALS
      AND METHODS: Retrospectively, 67 consecutive patients (28 men, 39 women; mean
      age, 63.25 +/- 18 years) from 2 centers with nonsevere PE diagnosed using CT and
      a clinical evaluation were included in the current study. Using consensus
      reading, 2 readers blinded to the patients' clinical outcomes quantified the
      right ventricle short axis to left ventricle short axis ratio in the axial plane,
      vascular measurements, reflux of contrast medium into the inferior vena cava and
      azygos vein, ventricular septal bowing, and clot load using the Qanadli scoring
      system. The Simplified Pulmonary Embolism Severity Index (sPESI) and pulmonary
      parenchymal findings were also evaluated. All CT pulmonary angiographic
      parameters were compared with the risk of death within 1 month using logistic
      regression analysis. RESULTS: Fifty-nine patients survived (88.1%), and 8
      patients (11.9%) died because of PE. The sPESI and 2 parenchymal findings
      (multiple wedge-shaped opacities or consolidation accompanied by a wedge-shaped
      opacity) were significantly related to mortality. In the univariate analysis,
      neither the cardiovascular CT parameters nor the clot burden was significant
      between the survivors and nonsurvivors (P > 0.05). CONCLUSIONS: In clinically
      nonsevere PE patients, the sPESI and significant parenchymal findings were the CT
      parameters related to 1-month mortality.

PMID- 25588189
TI  - Predicting outcome of substance abuse treatment in a feedback study: Can recovery
      curves be improved upon?
AB  - OBJECTIVE: The goal of the study was to evaluate whether enhanced normative
      feedback recovery curves are needed for treatment of substance use problems.
      METHOD: Patient predictors of outcome were examined using data from four
      substance abuse treatment clinics. RESULTS: Baseline severity of
      symptoms/functioning, employment, and craving were found to be associated with
      rate of change in symptoms/functioning. Several other variables were associated
      with rate of change in alcohol use, although in the opposite direction than found
      in efficacy trials. CONCLUSIONS: The results point to the complexity of designing
      feedback systems using normative recovery curves for those with substance use
      problems and highlight the important differences between real-world treatment of
      those with substance use problems compared to data from efficacy trials.

PMID- 25588191
TI  - Determination of free electron density in sequentially doped InxGa1-xAs by Raman
      spectroscopy.
AB  - The advent and exponential growth of mobile computing has spurred greater
      emphasis on the adoption of III-V compound semiconductors in device
      architectures. The introduction of high charge carrier densities within InxGa1
      xAs and the development of metrologies to quantitate the extent of doping have
      thus emerged as an urgent imperative. As an amphoteric dopant, Si begins to
      occupy anionic sites at high concentrations, thereby limiting the maximum carrier
      density that can be obtained upon Si doping of III-V semiconductors. Here, we
      present Raman results on sequentially doped In0.53Ga0.47As wherein sulfur
      monolayer doping is used to introduce additional carrier density to Si-doped
      samples. The sequential doping of Si and S allows for high carrier concentrations
      of up to 1.3 * 10(19) cm(-3) to be achieved without damaging the III-V lattice.
      The coupling of the plasmon in the doped samples to the longitudinal optic
      phonons allows Raman spectroscopy to serve as an excellent probe of the extent of
      dopant activation, charge carrier density, and the surface depletion region. In
      particular, the energy position of a high-frequency coupled mode (HFCM) that is
      detected above 400 cm(-1) is used to extract the free electron density in these
      samples. The extracted free electron densities are well correlated with measured
      sheet resistance values and the carrier densities deduced from Hall measurements.

PMID- 25588190
TI  - VEGF mRNA and protein concentrations in the developing human eye.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF), a well-characterized
      regulator of angiogenesis, has been mechanistically implicated in retinal
      neovascularization and in the pathogenesis of retinopathy of prematurity.
      However, the ontogeny of VEGF expression in the human fetal retina is not well
      known. Because retinal vasculature grows with gestational maturation, we
      hypothesized that VEGF expression also increases in the midgestation human fetal
      eye as a function of gestational age. METHODS: To identify changes in VEGF gene
      expression during normal human development, we measured VEGF mRNA by quantitative
      PCR and measured VEGF protein by enzyme-linked immunosorbent assay and western
      blots in 10-24 wk gestation fetal vitreous, retina, and serum. RESULTS: VEGF mRNA
      expression in the retina increased with gestational age. VEGF isoform A,
      particularly its VEGF121 splice variant, contributed to this positive
      correlation. Consistent with these findings, we detected increasing VEGF121
      protein concentrations in vitreous humor from fetuses of 10-24 wk gestation,
      while VEGF concentrations decreased in fetal serum. CONCLUSION: VEGF121 mRNA and
      protein concentrations increase with increasing gestational age in the developing
      human retina. We speculate that VEGF plays an important role in normal retinal
      vascular development, and that preterm delivery affects production of this
      vascular growth factor.

PMID- 25588192
TI  - Theoretical insight into the structural mechanism for the binding of vinblastine
      with tubulin.
AB  - Vinblastine (VLB) is one of vinca alkaloids with high cytotoxicity toward cancer
      cells approved for clinical use. However, because of drug resistance, toxicity,
      and other side effects caused from the use of VLB, new vinca alkaloids with
      higher cytotoxicity toward cancer cells and other good qualities need to develop.
      One strategy is to further study and better understand the essence why VLB
      possesses the high cytotoxicity toward cancer cells. In present work, by using
      molecular simulation, molecular docking, density functional calculation, and the
      crystal structure of alpha,beta-tubulin complex, we find two modes labeled in
      catharanthine moiety (CM) and vindoline moiety (VM) modes of VLB bound with the
      interface of alpha,beta-tubulin to probe the essence why VLB has the high
      cytotoxicity toward cancer cells. In the CM mode, nine key residues B-Ser178, B
      Asp179, B-Glu183, B-Tyr210, B-Asp226, C-Lys326, C-Asp327, C-Lys336, and C-Lys352
      from the alpha,beta-tubulin complex are determined as the active sites for the
      interaction of VLB with alpha,beta-tubulin. Some of them such as B-Ser178, B
      Glu183, B-Tyr210, B-Asp226, C-Lys326, C-Asp327, and C-Lys336 are newly identified
      as the active sites in present work. The affinity between VLB and the active
      pocket within the interface of alpha,beta-tubulin is -60.8 kJ mol(-1) in the CM
      mode. In the VM mode, that is a new mode established in present paper, nine
      similar key residues B-Lys176, B-Ser178, B-Asp179, B-Glu183, B-Tyr210, B-Asp226,
      C-Lys326, C-Asp327, and C-Lys336 from the alpha,beta-tubulin complex are found as
      the active sites for the interaction with VLB. The difference is from one key
      residue C-Lys352 in the CM mode changed to the key residue B-Lys176 in the VM
      mode. The affinity between VLB and the active pocket within the interface of
      alpha,beta-tubulin is -96.3 kJ mol(-1) in the VM mode. Based on the results
      obtained in present work, and because VLB looks like two faces, composed of CM
      and VM both to have similar polar active groups, to interact with the active
      sites, we suggest double-faces sticking mechanism for the binding of VLB to the
      interface of alpha,beta-tubulin. The double-faces sticking mechanism can be used
      to qualitatively explain high cytotoxicity toward cancer cells of vinca alkaloids
      including vinblastine, vincristine, vindestine, and vinorelbine approved for
      clinical use and vinflunine still in a phase III clinical trial. Furthermore,
      this mechanism will be applied to develop novel vinca alkaloids with much higher
      cytotoxicity toward cancer cells. 

PMID- 25588193
TI  - Characterization of hazardous and odorous volatiles emitted from scented candles
      before lighting and when lit.
AB  - Scented candles are known to release various volatile organic compounds (VOCs)
      including both pleasant aromas and toxic components both before lighting (off)
      and when lit (on). In this study, we explored the compositional changes of
      volatiles from scented candles under various settings to simulate indoor use.
      Carbonyl compounds and other VOCs emitted from six different candle types were
      analyzed under 'on/off' conditions. The six candle types investigated were: (1)
      Clean cotton (CT), (2) Floral (FL), (3) Kiwi melon (KW), (4) Strawberry (SB), (5)
      Vanilla (VN), and (6) Plain (PL). Although a large number of chemicals were
      released both before lighting and when lit, their profiles were noticeably
      distinguishable. Before lighting, various esters (n = 30) showed the most
      dominant emissions. When lit, formaldehyde was found to have the highest emission
      concentration of 2098 ppb (SB), 1022 ppb (CT), and 925 ppb (PL). In most lit
      scented candles, there was a general tendency to show increased concentrations of
      low boiling point compounds. For some scented candle products, the emission of
      volatiles occurred strongly both before lighting and when lit. For instance, in
      terms of TVOC (ppbC), the highest concentrations were observed from the KW
      product with their values of 12,742 (on) and 2766 ppbC (off). As such, the
      results suggest that certain scented candle products should act as potent sources
      of VOC emission in indoor environment, regardless of conditions--whether being
      lit or not.

PMID- 25588195
TI  - The effect of isorhamnetin glycosides extracted from Opuntia ficus-indica in a
      mouse model of diet induced obesity.
AB  - A diet rich in polyphenols can ameliorate some metabolic alterations associated
      with obesity and type 2 diabetes. Opuntia ficus-indica (OFI) is a plant rich in
      isorhamnetin glycosides and is highly consumed in Mexico. The purpose of this
      research was to determine the metabolic effect of an OFI extract on a mouse model
      of diet-induced obesity and in isolated pancreatic islets. OFI extract was added
      to a high fat (HF) diet at a low (0.3%) or high (0.6%) dose and administered to
      C57BL/6 mice for 12 weeks. Mice fed the HF diet supplemented with the OFI extract
      gained less body weight and exhibited significantly lower circulating total
      cholesterol, LDL cholesterol and HDL cholesterol compared to those fed the HF
      diet alone. The HF-OFI diet fed mice presented lower glucose and insulin
      concentration than the HF diet fed mice. However, the HF-OFI diet fed mice tended
      to have higher insulin concentration than control mice. The OFI extract
      stimulated insulin secretion in vitro, associated with increased glucose
      transporter 2 (GLUT2) and peroxisome proliferator-activated receptor gamma
      (PPARgamma) mRNA content. Furthermore, the OFI extract improved glucose
      tolerance, and additionally increased energy expenditure. These metabolic
      improvements were associated with reduced adipocyte size, increased hepatic IRS1
      tyr-608 and S6 K thr-389 phosphorylation. OFI isorhamnetin glycosides also
      diminished the hepatic lipid content associated with reduced mRNA expression of
      the endoplasmic reticulum stress markers and lipogenic enzymes and increased mRNA
      expression of genes related to fatty acid oxidation. Overall, the OFI extract
      prevented the development of metabolic abnormalities associated with diet-induced
      obesity. 

PMID- 25588194
TI  - A multimodal analysis of antipsychotic effects on brain structure and function in
      first-episode schizophrenia.
AB  - IMPORTANCE: Recent data suggest that treatment with antipsychotics is associated
      with reductions in cortical gray matter in patients with schizophrenia. These
      findings have led to concerns about the effect of antipsychotic treatment on
      brain structure and function; however, no studies to date have measured cortical
      function directly in individuals with schizophrenia and shown antipsychotic
      related reductions of gray matter. OBJECTIVE: To examine the effects of
      antipsychotics on brain structure and function in patients with first-episode
      schizophrenia, using cortical thickness measurements and administration of the AX
      version of the Continuous Performance Task (AX-CPT) during event-related
      functional magnetic resonance imaging. DESIGN, SETTING, AND PARTICIPANTS: This
      case-control cross-sectional study was conducted at the Imaging Research Center
      of the University of California, Davis, from November 2004 through July 2012.
      Participants were recruited on admission into the Early Diagnosis and Preventive
      Treatment Clinic, an outpatient clinic specializing in first-episode psychosis.
      Patients with first-episode schizophrenia who received atypical antipsychotics
      (medicated patient group) (n = 23) and those who received no antipsychotics
      (unmedicated patient group) (n = 22) and healthy control participants (n = 37)
      underwent functional magnetic resonance imaging using a 1.5-T scanner. MAIN
      OUTCOMES AND MEASURES: Behavioral performance was measured by trial accuracy,
      reaction time, and d'-context score. Voxelwise statistical parametric maps tested
      differences in functional activity during the AX-CPT, and vertexwise maps of
      cortical thickness tested differences in cortical thickness across the whole
      brain. RESULTS: Significant cortical thinning was identified in the medicated
      patient group relative to the control group in prefrontal (mean reduction [MR],
      0.27 mm; P < .001), temporal (MR, 0.34 mm; P = .02), parietal (MR, 0.21 mm; P =
      .001), and occipital (MR, 0.24 mm; P = .001) cortices. The unmedicated patient
      group showed no significant cortical thickness differences from the control group
      after clusterwise correction. The medicated patient group showed thinner cortex
      compared with the unmedicated patient group in the dorsolateral prefrontal cortex
      (DLPFC) (MR, 0.26 mm; P = .001) and temporal cortex (MR, 0.33 mm; P = .047).
      During the AX-CPT, both patient groups showed reduced DLPFC activity compared
      with the control group (P = .02 compared with the medicated group and P < .001
      compared with the unmedicated group). However, the medicated patient group
      demonstrated higher DLPFC activation (P = .02) and better behavioral performance
      (P = .02) than the unmedicated patient group. CONCLUSIONS AND RELEVANCE: These
      findings highlight the complex relationship between antipsychotic treatment and
      the structural, functional, and behavioral deficits repeatedly identified in
      schizophrenia. Although short-term treatment with antipsychotics was associated
      with prefrontal cortical thinning, treatment was also associated with better
      cognitive control and increased prefrontal functional activity. This study adds
      important context to the growing literature on the effects of antipsychotics on
      the brain and suggests caution in interpreting neuroanatomical changes as being
      related to a potentially adverse effect on brain function.

PMID- 25588196
TI  - Application of Molecular Diagnostics in Primary Detection of ESBL Directly from
      Clinical Specimens.
AB  - The infections caused by extended-spectrum beta-lactamase (ESBL)-producing
      organisms are associated with increased mortality. The real-time polymerase chain
      reaction (PCR) method, which enables detection of ESBLs directly from patients'
      clinical material, was developed. This study focused on blaCTX-M and blaSHV
      determination in endotracheal aspirates. Each sample was identified with standard
      microbiological procedures and simultaneously analyzed for the presence of
      nucleic acids, which encode CTX-M and SHV ESBL enzymes using real-time PCR. A
      total of 341 samples were investigated. In the set, 27 ESBL-positive samples were
      identified by phenotypic methods, while 60 positive samples were identified by
      the PCR method. Of the 60 PCR-positive samples, 58 were positive for the blaCTX
      M. In two samples, the ESBL blaSHV-ESBL gene was detected. One phenotypically
      positive sample was PCR negative. The real-time PCR assay does not require a
      cultivation step and therefore enables detection of ESBL in 6 hours. The rapid
      method is necessary for early and adequate antimicrobial treatment. 

PMID- 25588198
TI  - Wavelength- and efficiency-tunable plasmon-induced charge separation by the use
      of Au-Ag alloy nanoparticles.
AB  - TiO2 electrodes loaded with Au-Ag alloy nanoparticles, Ag content of which is
      about 0.25-0.90, exhibit stable anodic photocurrents due to plasmon-induced
      charge separation (PICS) in the presence of an electron donor. The PICS
      wavelength is blueshifted and the PICS efficiency is enhanced by increasing the
      Ag content in the nanoparticles. 

PMID- 25588199
TI  - Analysis of impurity effects on the coloration of corundum by laser-induced
      breakdown spectroscopy (LIBS).
AB  - Corundum was analyzed using laser-induced breakdown spectroscopy (LIBS) for
      impurity effects in their multiple colorings. Qualitative measurements were
      attained for impurities of chromium, magnesium, iron, and titanium in red,
      yellow, and blue samples. Moreover, treatment with a beryllium diffusion, which
      can modify corundum to obtain an attractive color, was tested in the yellow
      sample. In this work, most of the measurements were acquired using a laser pulse
      energy of 5 mJ and impurity emissions were appreciable. The signal-to-noise
      ratios were 11, 6.5, 10, and 4 for the Cr 425.44 nm, Fe 404.58 nm, Be 313.04 nm,
      and Mg 285.21 nm lines, respectively, for five laser shots. The amount of damage
      to the corundum samples was also monitored by measuring the craters after laser
      analysis. It was found that the crater size was about 30 MUm after 10 laser
      shots. As such, the damage to corundum sample is almost imperceptible after the
      LIBS analysis. 

PMID- 25588197
TI  - Functional near infrared spectroscopy as a potential biological assessment of
      addiction recovery: preliminary findings.
AB  - BACKGROUND: Addiction science has primarily utilized self-report, continued
      substance use, and relapse factors to explore the process of recovery. However,
      the entry into successful abstinence substantially reduces our assessment
      abilities. Advances in neuroscience may be the key to objective understanding,
      treating, and monitoring long-term success in addiction recovery. OBJECTIVES: To
      explore functional near infrared spectroscopy (fNIR) as a viable technique in the
      assessment of addiction-cue reactivity. Specifically, prefrontal cortex (PFC)
      activation to alcohol cues was explored among formally alcohol-dependent
      individuals, across varying levels of successful abstinence. The aim of the
      investigation was to identify patterns of PFC activation change consistent with
      duration of abstinence. METHODS: A total of 15 formally alcohol-dependent
      individuals, with abstinence durations ranging from 1 month to 10 years, viewed
      alcohol images during fNIR PFC assessment. Participants also subjectively rated
      the same images for affect and arousal level. RESULTS: Subjective ratings of
      alcohol cues did not significantly correlate with duration of abstinence. As
      expected, days of abstinence did not significantly correlate with neutral cue
      fNIR reactivity. However, for alcohol cues, fNIR results showed increased days of
      abstinence was associated with decreased activation within the dorsolateral and
      dorsomedial prefrontal cortex regions. CONCLUSIONS: The present results suggest
      that fNIR may be a viable tool in the assessment of addiction-cue reactivity.
      RESULTS also support previous findings on the importance of dorsolateral and
      dorsomedial PFC in alcohol-cue activation. The findings build upon these past
      results suggesting that fNIR-assessed activation may represent a robust
      biological marker of successful addiction recovery.

PMID- 25588200
TI  - Clinical competency evaluation of Brazilian chiropractic interns.
AB  - OBJECTIVE: This study compares the results of an objective structured clinical
      examination (OSCE) between 2 groups of students before an internship and after 6
      months of clinical practice in an internship. METHODS: Seventy-two students
      participated, with 36 students in each cohort. The OSCEs were performed in the
      simulation laboratory before the participants' clinical practice internship and
      after 6 months of the internship. Students were tested in 9 stations for clinical
      skills and knowledge. The same procedures were repeated for both cohorts. The t
      test was used for unpaired parametric samples and Fisher's exact test was used
      for comparison of proportions. RESULTS: There was no difference in the mean final
      score between the 2 groups (p = .34 for test 1; p = .08 for test 2). The
      performance of the students in group 1 was not significantly different when
      performed before and after 6 months of clinical practice, but in group 2 there
      was a significant decrease in the average score after 6 months of clinical
      practice. CONCLUSIONS: There was no difference in the cumulative average score
      for the 2 groups before and after 6 months of clinical practice in the
      internship. There were differences within the cohorts, however, with a
      significant decrease in the average score in group 2. Issues pertaining to test
      standardization and student motivation for test 2 may have influenced the scores.

PMID- 25588201
TI  - PEDOT-CNT coated electrodes stimulate retinal neurons at low voltage amplitudes
      and low charge densities.
AB  - OBJECTIVE: The aim of this study was to compare two different microelectrode
      materials--the conductive polymer composite poly-3,4-ethylenedioxythiophene
      (PEDOT)-carbon nanotube(CNT) and titanium nitride (TiN)--at activating spikes in
      retinal ganglion cells in whole mount rat retina through stimulation of the local
      retinal network. Stimulation efficacy of the microelectrodes was analyzed by
      comparing voltage, current and transferred charge at stimulation threshold.
      APPROACH: Retinal ganglion cell spikes were recorded by a central electrode (30
      MUm diameter) in the planar grid of an electrode array. Extracellular stimulation
      (monophasic, cathodic, 0.1-1.0 ms) of the retinal network was performed using
      constant voltage pulses applied to the eight surrounding electrodes. The
      stimulation electrodes were equally spaced on the four sides of a square (400 *
      400 MUm). Threshold voltage was determined as the pulse amplitude required to
      evoke network-mediated ganglion cell spiking in a defined post stimulus time
      window in 50% of identical stimulus repetitions. For the two electrode materials
      threshold voltage, transferred charge at threshold, maximum current and the
      residual current at the end of the pulse were compared. MAIN RESULTS: Stimulation
      of retinal interneurons using PEDOT-CNT electrodes is achieved with lower
      stimulation voltage and requires lower charge transfer as compared to TiN. The
      key parameter for effective stimulation is a constant current over at least 0.5
      ms, which is obtained by PEDOT-CNT electrodes at lower stimulation voltage due to
      its faradaic charge transfer mechanism. SIGNIFICANCE: In neuroprosthetic
      implants, PEDOT-CNT may allow for smaller electrodes, effective stimulation in a
      safe voltage regime and lower energy-consumption. Our study also indicates, that
      the charge transferred at threshold or the charge injection capacity per se does
      not determine stimulation efficacy.

PMID- 25588202
TI  - The emerging role of radiotherapy for desmoplastic melanoma and implications for
      future research.
AB  - The National Comprehensive Cancer Network (NCCN) 2014 guidelines are unclear
      about the role of radiotherapy in the management of desmoplastic melanoma. The
      guidelines specify that radiotherapy can be 'considered' for select patients with
      desmoplastic melanoma with narrow surgical margins. Patient selection criteria,
      including margins, are not well defined, causing considerable differences in
      practice patterns across the country. There are also several conflicting reports
      about the role of radiotherapy in improving postsurgical outcomes when other
      adverse pathological risks factors, such as increased Clark level, head and neck
      involvement, perineural invasion, positive margins, or recurrent disease, are
      also present. Recent data provide further clarification and insights into the
      role of radiotherapy. Thus, in light of the NCCN guidelines and the recently
      published series, we critically review the role of radiotherapy for desmoplastic
      melanoma. In our review, we highlight the published risk factors that predict for
      increased risk of recurrence after surgery. We also provide a comparison of
      surgical and radiation outcomes data, and then address areas for further
      research. 

PMID- 25588203
TI  - Let-7b overexpression leads to increased radiosensitivity of uveal melanoma
      cells.
AB  - Uveal melanoma (UM) is an intraocular malignant tumor in adults that is
      characterized by rapid progression and recurrence. Irradiation has become the
      primary therapy for UM patients who are not candidates for surgery. However,
      after large-dose fraction irradiation treatment, some patients undergo subsequent
      enucleation because of radiotherapy-related complications. This situation has
      raised concerns on how to optimize the effectiveness of radiation treatment.
      Recent investigations of microRNAs are changing our understanding of UM tumor
      biology and are helping to identify novel targets for radiotherapy. The
      radioresistant UM cell lines OM431 and OCM1 were selected and exposed to
      irradiation, and let-7b was found to be downregulated after exposure. We then
      confirmed that let-7b mimics could inhibit UM growth both in vitro and in vivo.
      More specifically, transfection with let-7b mimics markedly resensitized OCM1 and
      OM431 cells to irradiation by reducing the population of S-phase cells. Cyclin D1
      plays a vital role in cell cycle arrest, which is induced by let-7b
      overexpression. Cyclin D1 is also a target of let-7b and its expression is
      suppressed by upregulation of let-7b. Collectively, our results indicate that let
      7b overexpression can in turn downregulate cyclin D1 expression and enhance the
      radiosensitivity of UM through cell cycle arrest. Let-7b could serve as a marker
      for radiosensitivity and could enhance the therapeutic benefit of UM cell
      irradiation. 

PMID- 25588205
TI  - The supportive roles of religion and spirituality in end-of-life and palliative
      care of patients with cancer in a culturally diverse context: a literature
      review.
AB  - PURPOSE OF REVIEW: This is a literature review of the supportive roles of
      religion and spirituality (R/S) in end-of-life (EoL) and palliative care of
      patients with cancer in a culturally diverse context. This review examines 26
      noteworthy articles published between August 2013 and August 2014 from five well
      supported databases. RECENT FINDINGS: Current evidence shows that R/S evokes in
      patients the sources to find the necessary inner strengths, which includes
      perspective thinking, rituals for transcending immediate physical condition and
      modalities of coping with their oncological illnesses. R/S are not a
      monolithically experience for they always manifest themselves in diverse cultural
      settings. As such, R/S provide the individual and their families with a practical
      context and social memory, which includes traditions and social family practices
      for maintaining meaning and well-being. Nonetheless, although various dimensions
      of R/S show a link between cancer risk factors and well being in cancer patients,
      more specific dimensions of R/S need to be studied taking into account the
      individuals' particular religious and cultural contexts, so that R/S variables
      within that context can provide a greater integrative structure for understanding
      and to move the field forward. SUMMARY: Behavioral, cognitive and psychosocial
      scientists have taken a more in-depth look at the claims made in the past,
      suggesting that a relationship between R/S, cultural diversity and health exists.
      Case in point are the studies on EoL care, which have progressively considered
      the role of cultural, religion and spiritual diversity in the care of patients
      with oncological terminal illnesses. Beyond these facts, this review also shows
      that EoL supportive and palliative care providers could further enhance their
      practical interventions by being sensitive and supportive of cultural diversity.
      VIDEO ABSTRACT: http://links.lww.com/COSPC/A10

PMID- 25588204
TI  - The central role of meaning in adjustment to the loss of a child to cancer:
      implications for the development of meaning-centered grief therapy.
AB  - PURPOSE OF REVIEW: This review describes research on meaning and meaning-making
      in parents who have lost a child to cancer, suggesting the need for a meaning
      centered therapeutic approach to improve their sense of meaning, purpose, and
      identity and help with management of prolonged grief symptoms. RECENT FINDINGS:
      Several studies have demonstrated that parents bereaved by cancer experience
      unique meaning-related challenges associated with the caregiving and illness
      experience, including struggles with making sense of their loss, benefit-finding,
      their sense of identity and purpose, disconnection from sources of meaning, and
      sustaining a sense of meaning in their child's life. Meaning-centered grief
      therapy, adapted from meaning-centered psychotherapy, directly addresses these
      issues, highlighting the choices parents have in how they face their pain, how
      they honor their child and his/her living legacy, the story they create, and how
      they live their lives. SUMMARY: Given the important role that meaning plays in
      adjustment to the loss of a child to cancer, a meaning-focused approach such as
      meaning-centered grief therapy may help improve parents' sense of meaning and
      grief symptoms. It seems particularly appropriate for parents who lost a child to
      cancer because it does not pathologize their struggles and directly targets
      issues they frequently face.

PMID- 25588206
TI  - Palliative care issues in heart transplant candidates.
AB  - PURPOSE OF REVIEW: Heart failure is a serious condition and equivalent to
      malignant disease in terms of symptoms burden and mortality. Presently, only a
      comparatively small number of heart failure patients receive specialized
      palliative care. A literature search was conducted with the terms, palliative
      care and heart failure, using the electronic databases of PubMed and MEDLINE.
      RECENT FINDINGS: Nine-hundred and five articles were reviewed and of those, 78
      articles discussed clinical trials in palliative care and heart failure. A
      complex set of management tools and strategies were used and recommended,
      including but not limited to lifestyle modification, exercise programs, pain and
      sleep disorder management, and support in end-of-life care. Limited data are
      available of using palliative care in heart transplant candidates prior to
      transplant surgery. SUMMARY: Diminishing quality of life prevails throughout the
      course of chronic heart failure. Therefore, palliative care should be integrated
      into heart failure management. Heart transplant candidates may benefit from early
      palliative care involvement independent of the clinical course and outcome.
      Because of gaps in current scientific literature on palliative care, end-of-life
      care, and hospice care and the services rendered, further research is necessary
      to encourage healthcare professionals to introduce palliative care as an early
      resource in chronic disease progression.

PMID- 25588207
TI  - Parenting challenges in the setting of terminal illness: a family-focused
      perspective.
AB  - PURPOSE OF REVIEW: In the advanced stages of illness, families with dependent
      children experience disruption across all dimensions of family life. The need for
      family support during palliative care is well recognized, yet little is
      understood about how parents and their children navigate these difficult
      circumstances. This review summarizes the current body of research on parenting
      challenges in advanced cancer. RECENT FINDINGS: To date, the study of parental
      cancer has focused predominantly on the early stages of disease and its impact on
      children and adolescents. Less is known about how families with minor children
      prepare for parental loss. Evidence suggests that having dependent children
      influences parents' treatment decisions at the end of life, and that a central
      concern for children and parents is optimizing time spent together. Parents may
      feel an urgency to engage in accelerated parenting, and maintaining normalcy
      remains a consistent theme for the ill and healthy parent alike. There is a
      growing evidence base affirming the importance of responsive communication prior
      to death. SUMMARY: Advancing knowledge about the parenting experience at the end
      of life is critical for ensuring effective support to the entire family, as it
      accommodates and prepares for the loss of a vital member.

PMID- 25588208
TI  - Burden of caring: risks and consequences imposed on caregivers of those living
      and dying with advanced heart failure.
AB  - PURPOSE OF REVIEW: To summarize the latest research on the risks and consequences
      of the burden that may be imposed on informal carers of persons living and dying
      with advanced heart failure. RECENT FINDINGS: A systematic search in PubMed over
      the period 2013-2014 ultimately revealed 24 original articles included in this
      review. From this research update it can be concluded that the body of knowledge
      increased with more studies focusing on caregivers of patients with advanced
      heart failure. SUMMARY: Caregivers are important partners in care and their lives
      are seriously affected by the condition of advanced heart failure. Studies on the
      longitudinal effects of the caregiving role on caregiver's quality of life and on
      caregiver contributions to patient outcomes is still scarce. Focus of current
      research is moving towards relationship aspects. Dyadic-care typologies and the
      concept of incongruence within dyads in terms of conflicting perspectives on how
      to manage the heart failure are new and important concepts presented in studies
      presented in this review. Heart failure patients and their caregivers still lack
      sufficient palliative care and communication on prognosis and end-of-life care.
      More research is needed to determine the optimal time to start palliative
      interventions to support caregivers of patients with advanced heart failure.

PMID- 25588211
TI  - Getting a grasp of theories of sensorimotor control of the hand: identification
      of underlying neural mechanisms.

PMID- 25588209
TI  - Treatment with apixaban in a patient with recent chronic subdural haematoma: a
      case report.

PMID- 25588210
TI  - Approximating the detection limit of an infrared spectroscopic imaging microscope
      operating in an attenuated total reflection (ATR) modality: theoretical and
      empirical results for an instrument using a linear array detector and a 1.5
      millimeter germanium hemisphere internal reflection element.
AB  - Theoretical and empirical detection limits have been estimated for aripiprazole
      (analyte) in alpha lactose monohydrate (matrix model pharmaceutical formulation)
      using a micro-attenuated total reflection Fourier transform infrared (ATR FT-IR)
      spectroscopic imaging instrument equipped with a linear array detector and a 1.5
      mm germanium hemisphere internal reflection element (IRE). The instrument yielded
      a theoretical detection limit of 0.0035% (35 parts per million (ppm)) when
      operating under diffraction-limited conditions, which was 49 times lower than
      what was achieved with a traditional macro-ATR instrument operating under
      practical conditions (0.17%, 1700 ppm). However, these results may not be
      achievable for most analyses because the detection limits will be particle size
      limited, rather than diffraction limited, for mixtures with average particle
      diameters greater than 8.3 MUm (most pharmaceutical samples). For example, a
      theoretical detection limit of 0.028% (280 ppm) was calculated for an experiment
      operating under particle size-limited conditions where the average particle size
      was 23.4 MUm. These conditions yielded a detection limit of 0.022% (220 ppm) when
      measured empirically, which was close to the theoretical value and only eight
      times lower than that of a faster, more simplistic macro-ATR instrument.
      Considering the longer data acquisition and processing times characteristic of
      the micro-ATR imaging approach (minutes or even hours versus seconds), the cost
      benefit ratio may not often be favorable for the analysis of analytes in matrices
      that exhibit only a few overlapping absorptions (low-interfering matrices such as
      alpha lactose monohydrate) using this technique compared to what can be achieved
      using macro-ATR. However, the advantage was significant for detecting analytes in
      more complex matrices (those that exhibited several overlapping absorptions with
      the analyte) because the detection limit of the macro-ATR approach was highly
      formulation dependent while that of the micro-ATR imaging technique was not. As a
      result, the micro-ATR imaging technique is expected to be more valuable than
      macro-ATR for detecting analytes in high-interfering matrices and in products
      with unknown ingredients (e.g., illicit tablets, counterfeit tablets, and unknown
      powders). 

PMID- 25588212
TI  - Byproduct promoted regioselective sulfenylation of indoles with sulfinic acids.
AB  - An unprecedented method to synthesise 3-sulfenylindoles is demonstrated via
      byproduct promoted sulfenylation of indoles with sulfinic acids in the absence of
      an external catalyst. The reaction selectively afforded structurally diverse
      indole thioethers in good to excellent yields in 1,2-dichloroethane at 80 
      degrees C. 

PMID- 25588214
TI  - TiO2 immobilized on Manihot carbon: optimal preparation and evaluation of its
      activity in the decomposition of indigo carmine.
AB  - Applications of carbon-TiO2 materials have attracted attention in nanotechnology
      due to their synergic effects. We report the immobilization of TiO2 on carbon
      prepared from residues of the plant Manihot, commercial TiO2 and glycerol. The
      objective was to obtain a moderate loading of the anatase phase by preserving the
      carbonaceous external surface and micropores of the composite. Two preparation
      methods were compared, including mixing dry precursors and immobilization using a
      glycerol slurry. The evaluation of the micropore blocking was performed using
      nitrogen adsorption isotherms. The results indicated that it was possible to use
      Manihot residues and glycerol to prepare an anatase-containing material with a
      basic surface and a significant SBET value. The activities of the prepared
      materials were tested in a decomposition assay of indigo carmine. The TiO2/carbon
      eliminated nearly 100% of the dye under UV irradiation using the optimal
      conditions found by a Taguchi L4 orthogonal array considering the specific
      surface, temperature and initial concentration. The reaction was monitored by UV
      Vis spectrophotometry and LC-ESI-(Qq)-TOF-MS, enabling the identification of some
      intermediates. No isatin-5-sulfonic acid was detected after a 60 min
      photocatalytic reaction, and three sulfonated aromatic amines, including 4-amino
      3-hydroxybenzenesulfonic acid, 2-(2-amino-5-sulfophenyl)-2-oxoacetic acid and 2
      amino-5-sulfobenzoic acid, were present in the reaction mixture. 

PMID- 25588213
TI  - Ponicidin induces apoptosis via JAK2 and STAT3 signaling pathways in gastric
      carcinoma.
AB  - Ponicidin has a variety of biological effects such as immunoregulatory and anti
      inflammatory functions as well as anti-viral functions especially in the upper
      respiratory tract infection. This study was aimed to elucidate the antitumor
      effect of ponicidin in gastric carcinoma MKN28 cells and the possible molecular
      mechanism involved. Cell viability was measured by the Cell Count Kit-8 (CCK8).
      Cell apoptosis was assessed by flow cytometry as well as cell cycle and reactive
      oxygen species (ROS) analysis. Western blot analysis was used to detect the
      active form of caspase-3 as well as Bax and B-cell lymphoma-2 (Bcl-2) expressions
      after cells were treated with different concentrations of ponicidin. The results
      revealed that ponicidin could inhibit the growth of MKN28 cells significantly in
      both a time- and dose-dependent manner. The cell cycle was blocked and ROS
      generation was increased after the cells were treated with ponicidin. Bcl-2
      expression was down-regulated remarkably while Bax expression and the active form
      of caspase-3 were increased after apoptosis occurred. We therefore conclude that
      ponicidin exhibited significant growth inhibition of gastric carcinoma cell line
      MKN28 and induced apoptosis of MKN28 cells via the signaling pathway regulated by
      Janus kinase 2 (JAK2) and signal transducers and activators of transcription 3
      (STAT3). Ponicidin may serve as a potential therapeutic agent for gastric
      carcinoma. 

PMID- 25588215
TI  - Acetic acid can catalyze succinimide formation from aspartic acid residues by a
      concerted bond reorganization mechanism: a computational study.
AB  - Succinimide formation from aspartic acid (Asp) residues is a concern in the
      formulation of protein drugs. Based on density functional theory calculations
      using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the
      possibility that acetic acid (AA), which is often used in protein drug
      formulation for mildly acidic buffer solutions, catalyzes the succinimide
      formation from Asp residues by acting as a proton-transfer mediator. The proposed
      mechanism comprises two steps: cyclization (intramolecular addition) to form a
      gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps
      are catalyzed by an AA molecule, and the first step was predicted to be rate
      determining. The cyclization results from a bond formation between the amide
      nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part
      of an extensive bond reorganization (formation and breaking of single bonds and
      the interchange of single and double bonds) occurring concertedly in a cyclic
      structure formed by the amide NH bond, the AA molecule and the side-chain C=O
      group and involving a double proton transfer. The second step also involves an AA
      mediated bond reorganization. Carboxylic acids other than AA are also expected to
      catalyze the succinimide formation by a similar mechanism. 

PMID- 25588216
TI  - Caution is required in interpretation of mutations in the voltage sensing domain
      of voltage gated channels as evidence for gating mechanisms.
AB  - The gating mechanism of voltage sensitive ion channels is generally considered to
      be the motion of the S4 transmembrane segment of the voltage sensing domains
      (VSD). The primary supporting evidence came from R -> C mutations on the S4
      transmembrane segment of the VSD, followed by reaction with a
      methanethiosulfonate (MTS) reagent. The cys side chain is -SH (reactive form -S
      ); the arginine side chain is much larger, leaving space big enough to
      accommodate the MTS sulfonate head group. The cavity created by the mutation has
      space for up to seven more water molecules than were present in wild type, which
      could be displaced irreversibly by the MTS reagent. Our quantum calculations show
      there is major reorientation of three aromatic residues that face into the cavity
      in response to proton displacement within the VSD. Two phenylalanines reorient
      sufficiently to shield/unshield the cysteine from the intracellular and
      extracellular ends, depending on the proton positions, and a tyrosine forms a
      hydrogen bond to the cysteine sulfur with its side chain -OH. These could produce
      the results of the experiments that have been interpreted as evidence for
      physical motion of the S4 segment, without physical motion of the S4 backbone.
      The computations strongly suggest that the interpretation of cysteine
      substitution reaction experiments be re-examined in the light of these
      considerations.

PMID- 25588219
TI  - RETRACTION: Barkhordari A, et al. The glycoprofile patterns of endothelial cells
      in usual interstitial pneumonia. Int J Occup Environ Med 2014;5:201-7.

PMID- 25588217
TI  - Protection of retina by mini-alphaA in NaIO3-induced retinal pigment epithelium
      degeneration mice.
AB  - BACKGROUND: Studies have shown that mini-alphaA can protect retinal pigment
      epithelium (RPE) cells from apoptosis. However, no in vivo study concerning the
      anti-apoptotic function of mini-alphaA has been conducted yet. METHODS: MTT
      assay, HE staining and TUNEL assay were used to assess levels of cells, and an
      animal model was established to examine the protective effects of mini-alphaA
      against NaIO3-induced RPE cell apoptosis. Western blot analysis and RT-qPCR were
      performed to explore the possible mechanism of mini-alphaA's protective function
      against NaIO3-induced RPE cell apoptosis. RESULTS: RESULTS from in vivo and
      animal experiments showed that mini-alphaA antagonized NaIO3-induced RPE cell
      apoptosis. Further investigation into how mini-alphaA provided protection against
      NaIO3-induced RPE cell apoptosis showed that mini-alphaA reduced NaIO3-induced
      RPE cell apoptosis and autophagy. In addition, unfolded protein response was also
      involved in the protective effects of mini-alphaA against NaIO3-induced RPE cell
      apoptosis. CONCLUSIONS: mini-alphaA can antagonize RPE cell apoptosis induced by
      NaIO3. A possible mechanism is by inhibition of apoptosis by repressing autophagy
      and endoplasmic reticulum stress.

PMID- 25588220
TI  - Why is redundant publication a problem?

PMID- 25588218
TI  - Activation of the ubiquitin proteasome pathway by silk fibroin modified chitosan
      nanoparticles in hepatic cancer cells.
AB  - Silk fibroin (SF) is a protein with bulky hydrophobic domains and can be easily
      purified as sericin-free silk-based biomaterial. Silk fibroin modified chitosan
      nanoparticle (SF-CSNP), a biocompatible material, has been widely used as a
      potential drug delivery system. Our current investigation studied the bio-effects
      of the SF-CSNP uptake by liver cells. In this experiment, the characterizations
      of SF-CSNPs were measured by particle size analysis and protein assay. The
      average size of the SF-CSNP was 311.9 +/- 10.7 nm, and the average zeta potential
      was +13.33 +/- 0.3 mV. The SF coating on the SF-CSNP was 6.27 +/- 0.17 MUg/mL.
      Moreover, using proteomic approaches, several proteins involved in the ubiquitin
      proteasome pathway were identified by analysis of differential protein
      expressions of HepG2 cell uptake the SF-CSNP. Our experimental results have
      demonstrated that the SF-CSNP may be involved in liver cancer cell survival and
      proliferation. 

PMID- 25588221
TI  - Attitude of medical students towards occupational safety and health: a multi
      national study.
AB  - BACKGROUND: Work-related diseases contribute immensely to the global burden of
      diseases. Better understanding of attitudes of health care workers towards
      occupational safety and health (OSH) is important for planning. OBJECTIVE: To
      assess the attitude of medical students towards OSH around the globe. METHODS: A
      questionnaire assessing the attitude towards OSH was administered to medical and
      paramedical students of 21 Medical Universities across the globe. In the current
      study 1895 students, aged 18-36 years, from 17 countries were included. After
      having performed a principal components analysis, the associations of interest
      between the identified components and other socio demographic characteristics
      were assessed by multivariate linear regression. RESULTS: Principal component
      analysis revealed 3 components. Students from lower and lower-middle-income
      countries had a more positive attitude towards OSH, but the importance of OSH was
      still rated higher by students from upper-income countries. Although students
      from Asian and African continents showed high interest for OSH, European and
      South-Central American students comparatively rated importance of OSH to be
      higher. Paramedical students had more positive attitude towards OSH than medical
      students. CONCLUSION: The attitude of students from lower-income and lower-middle
      income towards importance of OSH is negative. This attitude could be changed by
      recommending modifications to OSH courses that reflect the importance of OSH.
      Since paramedical students showed more interest in OSH than medical students,
      modifications in existing health care system with major role of paramedics in OSH
      service delivery is recommended.

PMID- 25588222
TI  - Effects of long-term exposure to hydrogen sulfide on human red blood cells.
AB  - BACKGROUND: Hydrogen sulfide (H2S) exhibits both physiological and toxicological
      roles in the biological systems. Acute exposure to high levels of H2S is life
      threatening while long-term exposure to ambient levels of H2S elicits human
      health effects. OBJECTIVE: To study the harmful effects of long-term exposure to
      low levels of H2S on human blood cells. METHODS: 110 adult workers from Iran who
      were occupationally exposed to 0-90 ppb H2S for 1-30 years were studied. The
      participants aged between 18 and 60 years and were exposed directly or indirectly
      to sulfur compounds (exposed group). The origin of H2S was natural gas processing
      plants. A control group consisting of 110 males who were not in contact with H2S
      was also studied. For all participants, hematological profile including total
      hemoglobin and red blood cell count and sulfhemoglobin, methemoglobin levels were
      measured. RESULTS: Among all parameters evaluated in this study the mean
      methemoglobin and sulfhemoglobin levels were significantly higher among workers
      who were exposed to sulfur compounds than the control group. Major differences
      throughout the study period for sulfhemoglobinemia among exposed groups were
      observed. CONCLUSION: Long-term exposure to even low levels of H2S in workplaces
      may have potential harmful effects on human health.

PMID- 25588223
TI  - Benchmarking of percutaneous injuries at the Ministry of Health hospitals of
      Saudi Arabia in comparison with the United States hospitals participating in
      Exposure Prevention Information Network (EPINetTM).
AB  - BACKGROUND: Exposure to blood-borne pathogens from needle-stick and sharp
      injuries continues to pose a significant risk to health care workers. These
      events are of concern because of the risk to transmit blood-borne diseases such
      as hepatitis B virus, hepatitis C virus, and the human immunodeficiency virus.
      OBJECTIVE: To benchmark different risk factors associated with needle-stick
      incidents among health care workers in the Ministry of Health hospitals in the
      Kingdom of Saudi Arabia compared to the US hospitals participating in Exposure
      Prevention Information Network (EPINetTM). METHODS: Prospective surveillance of
      needle-stick and sharp incidents carried out during the year 2012 using EPINetTM
      ver 1.5 that provides uniform needle stick and sharp injury report form. RESULTS:
      The annual percutaneous incidents (PIs) rate per 100 occupied beds was 3.2 at the
      studied MOH hospitals. Nurses were the most affected job category by PIs (59.4%).
      Most PIs happened in patients' wards in the Ministry of Health hospitals (34.6%).
      Disposable syringes were the most common cause of PIs (47.20%). Most PIs occurred
      during use of the syringes (36.4%). CONCLUSION: Among health care workers, nurses
      and physicians appear especially at risk of exposure to PIs. Important risk
      factors of injuries include working in patient room, using disposable syringes,
      devices without safety features. Preventive strategies such as continuous
      training of health care workers with special emphasis on nurses and physicians,
      encouragement of reporting of such incidents, observation of sharp handling,
      their use and implementation of safety devices are warranted.

PMID- 25588224
TI  - Metabolic syndrome: a common problem among office workers.
AB  - BACKGROUND: Metabolic syndrome (MSx) is associated with several health problems.
      Workers are an important part of any organization. OBJECTIVE: To determine the
      prevalence of MSx and related variables among office workers. METHODS: This cross
      sectional study evaluated 1488 office workers in Qom province, Central Iran, by
      using a multi-stage cluster sampling. Diagnosis of MSx was based on blood HDL
      cholesterol, triglyceride, and fasting blood sugar (FBS) levels and waist
      circumference, and blood pressure. RESULTS: The overall prevalence of MSx was
      35.9% (95% CI 33.5% to 38.3%), higher in men (37.2%) than in women (20.6%), and
      increased with age. The most common laboratory findings of MSx were
      hypertriglyceridemia (45.9%) and low HDL-cholesterol level (45.5%). Office
      workers with MSx had a significantly (p<0.001) higher body mass index than those
      without MSx. Lack of regular leisure time physical activity (p=0.003), and low
      intake of fruits (p=0.02) were associated with MSx. CONCLUSION: The prevalence of
      MSx was very high among office workers. Workplace health improvement programs
      through identifying and preventing MSx are necessary for improvement of staff's
      health.

PMID- 25588225
TI  - Respiratory disorders associated with occupational inhalational exposure to
      bioaerosols among wastewater treatment workers of petrochemical complexes.
AB  - BACKGROUND: Workers in wastewater treatment plants are exposed to a wide range of
      chemicals as well as biological contaminants. OBJECTIVE: To ascertain whether
      exposure to bio-aerosols under the normal working conditions in wastewater
      treatment plants is associated with any significant changes in the prevalence of
      respiratory symptoms and lung function capacities. METHODS: 198 employees of
      wastewater treatment plants and 99 unexposed persons were studied. American
      thoracic society (ATS) standard respiratory symptom questionnaire was used to
      determine the prevalence of respiratory symptoms. Pulmonary function tests were
      conducted for each participant. RESULTS: The prevalence of respiratory symptoms
      among exposed persons was significantly higher than that of unexposed people.
      Mean values of most pulmonary function test parameters were significantly lower
      in the exposed compared to the comparison group persons. CONCLUSION: Increased
      prevalence of respiratory symptoms and decrements in pulmonary function test
      parameters may be attributed to exposure to bio-aerosols released from wastewater
      treatment plants.

PMID- 25588226
TI  - Serum neuron-specific enolase, biogenic amino-acids and neurobehavioral function
      in lead-exposed workers from lead-acid battery manufacturing process.
AB  - BACKGROUND: The interaction between serum neuron-specific enolase (NSE), biogenic
      amino-acids and neurobehavioral function with blood lead levels in workers
      exposed to lead form lead-acid battery manufacturing process was not studied.
      OBJECTIVE: To evaluate serum NSE and biogenic amino-acids (dopamine and
      serotonin) levels, and neurobehavioral performance among workers exposed to lead
      from lead-acid storage battery plant, and its relation with blood lead levels
      (BLLs). METHODS: In a cross-sectional study, we performed biochemical and
      neurobehavioral function tests on 146 workers exposed to lead from lead-acid
      battery manufacturing process. BLLs were assessed by an atomic absorption
      spectrophotometer. Serum NSE, dopamine and serotonin were measured by ELISA.
      Neurobehavioral functions were assessed by CDC-recommended tests---simple
      reaction time (SRT), symbol digit substitution test (SDST), and serial digit
      learning test (SDLT). RESULTS: There was a significant correlation (r 0.199,
      p<0.05) between SDST and BLL. SDLT and SRT had also a significant positive
      correlation (r 0.238, p<0.01). NSE had a negative correlation (r -0.194, p<0.05)
      with serotonin level. Multiple linear regression analysis revealed that both SRT
      and SDST had positive significant associations with BLL. SRT also had a positive
      significant association with age. CONCLUSION: Serum NSE cannot be used as a
      marker for BLL. The only domain of neurobehavioral function tests that is
      affected by increased BLL in workers of lead-acid battery manufacturing process
      is that of the "attention and perception" (SDST).

PMID- 25588229
TI  - Guest editorial: pittcon 2015.

PMID- 25588230
TI  - Meet the new president: Diane Parry.

PMID- 25588227
TI  - Knowledge and attitude towards asbestos hazards among asbestos workers in India.

PMID- 25588231
TI  - Analysis of pure tar substances (polycyclic aromatic hydrocarbons) in the gas
      stream using ultraviolet visible (UV-Vis) spectroscopy and multivariate curve
      resolution (MCR).
AB  - The analysis of tar, mostly characterized as polycyclic aromatic hydrocarbons
      (PAHs), describes a topic that has been researched for years. An online analysis
      of tar in the gas stream in particular is needed to characterize the tar
      conversion or formation in the biomass gasification process. The online analysis
      in the gas is carried out with ultraviolet-visible (UV-Vis) spectroscopy (190-720
      nm). This online analysis is performed with a measuring cell developed by the
      Fraunhofer Institute for Chemical Technology (ICT). To this day, online tar
      measurements using UV-Vis spectroscopy have not been carried out in detail.
      Therefore, PAHs are analyzed as follows. The measurements are split into
      different steps. The first step to prove the online method is to vaporize single
      tar substances. These experiments show that a qualitative analysis of PAHs in the
      gas stream with the used measurement setup is possible. Furthermore, it is shown
      that the method provides very exact results, so that a differentiation of various
      PAHs is possible. The next step is to vaporize a PAH mixture. This step consists
      of vaporizing five pure substances almost simultaneously. The interpretation of
      the resulting data is made using a chemometric interpretation method, the
      multivariate curve resolution (MCR). The verification of the calculated results
      is the main aim of this experiment. It has been shown that the tar mixture can be
      analyzed qualitatively and quantitatively (in arbitrary units) in detail using
      the MCR. Finally it is the main goal of this paper to show the first steps in the
      applicability of the UV-Vis spectroscopy and the measurement setup on online tar
      analysis in view of characterizing the biomass gasification process. Due to that,
      the gasification plant (at the laboratory scale), developed and constructed by
      the Fraunhofer ICT, has been used to vaporize these substances. Using this
      gasification plant for the experiments enables the usage of the measurement setup
      also for the spectroscopic analysis of the tar formation during the biomass
      gasification. 

PMID- 25588233
TI  - Festschrift in honour of David Smith.

PMID- 25588232
TI  - Ionizing radiation induces structural and functional damage on the molecules of
      rat brain homogenate membranes: a Fourier transform infrared (FT-IR)
      spectroscopic study.
AB  - Humans can be exposed to ionizing radiation, due to various reasons, whose
      structural effects on biological membranes are not well defined. The current
      study aims to understand the ionizing radiation-induced structural and functional
      alterations in biomolecules of brain membranes using Fourier transform infrared
      (FT-IR) spectroscopy using rat animal models. For this purpose, 1000 cGy of
      ionizing radiation was specifically directed to the head of Sprague Dawley rats.
      The rats were decapitated after 24 h. The results revealed that the lipid-to
      protein ratio decreased and that irradiation caused lipid peroxidation and
      increases in the amounts of olefinic =CH, carbonyl, and methylene groups of
      lipids. In addition, ionizing radiation induced a decrease in membrane fluidity,
      disordering of membrane lipids, strengthening of the hydrogen bonding of the
      phosphate groups of lipid head-groups, and weakening in the hydrogen bonding of
      the interfacial carbonyl groups of lipids. Radiation further caused significant
      decrements in the alpha-helix and turns, and significant increments in the beta
      sheet and random coil contents in the protein structure. Hierarchical cluster
      analyses, performed in the whole region (3030-1000 cm(-1)), lipid (3030-2800 cm(
      1)), and protein (1700-1600 cm(-1)) regions separately, successfully
      differentiated the control and irradiated groups of rat brain membranes and
      showed that proteins in the membranes are affected more than lipids from the
      damages induced with ionizing radiation. As a result, the current study showed
      that FT-IR spectroscopy can be used successfully as a novel method to monitor
      radiation-induced alterations on biological membranes. 

PMID- 25588234
TI  - How states are expanding Medicaid to low-income adults through Section 1115
      waiver demonstrations.
AB  - In the wake of the Supreme Court's 2012 decision making state expansion of
      Medicaid to more adults optional under the Affordable Care Act, several states
      have received approval to combine such expansion with broader Medicaid reforms.
      They are doing so under Section 1115 of the Social Security Act, which authorizes
      Medicaid demonstrations that further program objectives. State demonstrations
      approved so far combine expanded adult coverage with changes in that coverage and
      in how the states deliver and pay for health care. These states have focused
      especially on expanding the use of private health insurance, requiring
      beneficiaries to pay premiums, and incentivizing them to choose cost-effective
      care. By enabling states to link wider program reforms to the adult expansion,
      Section 1115 has allowed them to better align Medicaid with local political
      conditions while extending insurance to more than 1 million adults who would
      otherwise lack a pathway to coverage.

PMID- 25588235
TI  - Implementing the Affordable Care Act: state approaches to premium rate reforms in
      the individual health insurance market.
AB  - The Affordable Care Act protects people from being charged more for insurance
      based on factors like medical history or gender and establishes new limits on how
      insurers can adjust premiums for age, tobacco use, and geography. This brief
      examines how states have implemented these federal reforms in their individual
      health insurance markets. We identify state rating standards for the first year
      of full implementation of reform and explore critical considerations weighed by
      policymakers as they determined how to adopt the law's requirements. Most states
      took the opportunity to customize at least some aspect of their rating standards.
      Interviews with state regulators reveal that many states pursued implementation
      strategies intended primarily to minimize market disruption and premium shock and
      therefore established standards as consistent as possible with existing rules or
      market practice. Meanwhile, some states used the transition period to strengthen
      consumer protections, particularly with respect to tobacco rating.

PMID- 25588236
TI  - [Epidemiology of chronic bronchopulmonary diseases II].

PMID- 25588237
TI  - [The antalgic and antiinflammatory effect of the total extract from Helleborus
      species (the Boicil product), in rat].

PMID- 25588238
TI  - [[100 years from the discovery of the Koch's bacillus].

PMID- 25588239
TI  - [Possibilities and limitations in the esophageal cancer surgery].

PMID- 25588240
TI  - [Mediastinal giant cystic dysembrioma].
AB  - A 42 years old man with evident distortion in the lower 2/3 of the right
      hemithorax, area in which he presents a compression syndrome and radiologically a
      bulky opacity with tumoral aspect that shifts the heart and mediastinum to the
      left, is presented. The thoracotomy reveals a giant cystic formation containing
      approximatively 7 l. of rough magma into which hair, cartilaginous and bone
      tissue are identified. After their removal the cystic wall (1 cm thick) is
      excised except for an implantation area of 4/8 cm adherent to the large vessels
      and pericardium. The postoperative evolution is uneventful. The histopathological
      examination confirms the diagnostis of MCD identifying derivatives from all 3
      embryonic sheets.

PMID- 25588241
TI  - [Preleukaemia].

PMID- 25588242
TI  - [Ways of bacterial attachment to mucous surfaces and possibilities of preventing
      the infections].

PMID- 25588243
TI  - [Investigations of the left ventricular dynamics in stable-angina pectoris (AP)].
AB  - The investigations were carried out in 78 patients with stable AP without
      myocardiaI infarction in their case history and in 30 controls all distributed in
      three series: I = 37 patients with AP and marked alterations of ventricular
      repolarization (ST depression >= 52 mm and T negative waves >= 2 mm); II = 41
      patients with AP and normal ECG and III = 30 controls, clinically and ECG normal,
      of similar age with the patients in the I and II series. The investigations of
      the left ventricular systole periods also rendered evident in the patients with
      AP important alterations of ventricular repolarization (Ist series): prolonged
      preejection period (PEP) due to the izovolumetric contraction time (IVCT),
      shortening of the ejection time (LVET) and decrease of PEP/LVET ratio as well as
      the significant increase of S(IV)/S(I) ratio. Although slightly shortened in this
      series, the electromechanic systole (QS(II)) does not present statistically
      significant alterations, the prolonged PEP being partially counter-balaced by the
      shortened LVET. The most sensitive index seems to be the PEP/LVET ratio. The
      alterations' of the left ventricular systole periods become evident late in the
      course of the disease, when significant ischemic lesions are present this the
      method has no value in determining an early diagnosis. On the other hand this
      type of investigation is an useful quantitative method for estimating the
      functional state of the cardiac muscle in the patients with the diagnosis of AP
      (stage diagnosis of AP) and subsequent evolution (repeated records).

PMID- 25588245
TI  - [Bordeline states and their significance in psychiatry].
AB  - The authors critically analyse the tendency of conceptualizing some difficult to
      classify psycho-pathological states, the symptoms and clinical dynamics of which
      would be characteristic, in a psycho-analytical interpretation, to a
      nosologically distinct category termed "bordeline states". The authors'
      orientation and clinical observations related to the data in the literature lead
      to the specification of those situations in which this term can be used in the
      psychiatric diagnosis, preferably under its original lexical form and with the
      specification of the substantiating concept. Due to the looseness and ununitary
      interpretation of the "bordeline states" situations, for the clinical cases that
      correspond to the diagnostic criteri, it is prefered the term of psychopathy,
      which although controversial, has a more statutory use in psychiatry.

PMID- 25588244
TI  - [Benign solitary thyroid nodule (BSTN)].
AB  - Out of a series of 210 patients (193 women and 17 men) with BSTN, 62% presented
      an warm nodule, 25.2% a hot nodule and 11.9% a cold nodule. The highest incidence
      of the nodule was noticed round the age of 40-50 years. The most common site was
      the middle and lower area of the right thyroid lobe. The thyroid scintigram
      provided orientative data regarding the nature of BSTN, the treatment indication
      being the surgical intervention. Histopathologically, polymorphic aspects ranging
      from anizofollicular adenoma, adenomatous proliferations areas and
      hyperfunctional aspect to degenerative sclerous alterations and
      lymphoplasmocitary infiltrations were noticed. The current hypotheses regarding
      the etiopathogeny of nodule forming process are discussed. Based on some data in
      the literature, we consider the nodularization of the thyroid gland as a
      reactional zone functional desynchronization in the conditions of some great
      variations of the iodate intaxe.

PMID- 25588246
TI  - [Possibilities of employing the extracts from Bulbus cepae in dermopreparations].

PMID- 25588247
TI  - [Gastric stump cancer].
AB  - The cases of gastric stump cancer recorded at the III-rd Surgical Clinic of Iaoi
      during the last 5 years are analysed. Based upon the personal experience and data
      in the literature 7 cases are discussed. Out of the 7 cases, in 3 an initial
      resection for gastric ulcer and in 4 for duodenal ulcer was performed 17-40 years
      previously (with an average of 26 years). All the patients presented Bilroth II
      anastomoses. The diagnosis was determined by radiological, endoscopic and
      endobioptic examinations after a mean interval of 10 month since the occurence of
      the clinical symptoms. The site of the lesion was the following: in 3 cases on
      the anastomosis line and in 4 on the reminder of the stump. Out of the 7 cases, 5
      were operable and in 4 the resection was completed. Two days post-operatively a
      death was recorded. The conclusions of this paper insist upon the fact that the
      occurance of the tumor on the gastric resection stump mainly depends on the
      initial lesion (gastric lesion) and less on the type of anastomosis. The long
      term surveillance of the gastric resection patients is thus essential.

PMID- 25588248
TI  - [On tihe diagnosis, treatment and late results in prostatic carcinoma].
AB  - 209 cases of prostatic carcinoma out of which 112 with coexistance adenoma-cancer
      and 97 true carcinomas are analysed. The diagnosis was determined by histological
      examination of adenomectomy or transrectal or perineal needle biopsy specimens.
      Out of the 112 adenoma-cancer cases in 65 the existence of a single or multiple
      nodule, having a more firm consistency, was noticed and in 47 the rendering
      evident of the malignant lesion was a histological surprise of the adenomectomy
      specimens. The age distribution is the following: 42.7% between the age of 71 and
      80, 31.5% between 61 and 70, 13% between 51 and 60, 70% between 45 and 50, 5.8%
      above 80. The treatments employed were: 112 adenomectomies, 50 removals of the
      pelviprostatic capsular ligament associated with bilateral castration and
      hormonotherapy and 47 estrogen hormonotherapies. The importance of the
      histological examination of the surgical specimens (in the case of adenomectomy)
      and biopsy for specifying the malignant nature of the prostatic alterations is
      emphasized.

PMID- 25588250
TI  - [Methodolgy and interpretation in the study of the complement system in chronic
      hepatitis].
AB  - The determination of the total hemolitic serum complement, as a screening test
      for investigating the activity of the entire complement system and the
      measurement of the C3 fraction consumption, has now gained a peculiar importance
      due to its contribution to the clearing up of some problems regarding the
      pathogeny an diagnosis of chronic hepatitis. The correlation of these values
      alterations with the presence of antiglobulinic antigens orientatively suggests
      the presence of immune complexes taking part in the maintainance of the
      inflammatory hepatic process.

PMID- 25588249
TI  - [Cerebellar contusive syndrome].
AB  - As part of the localized encephalic contusions, the cerebellar contusion, by its
      etiopathogenic, clinic, paraclinic, therapeutic and prognostic aspects represents
      a distinct individuality. Studying a series of 30 cases of cerebellar contusions
      the authors notice the increased incidence in children (28 cases), the cerebellar
      vulnerability in children being explained by the high site and increased
      elasticity of the occipital bone as well as by the nape muscles thinness. The
      clinical syndrome, more common of archicerebellar type, can occur alone or
      associated with a minor or mild diffuse mental shock. The paraclinic
      investigation is reduced to lombar puncture, cranial radiography and EEG. The
      evolution, especially in children, is towards healing in 2-3 weeks of
      conservative treatment.

PMID- 25588251
TI  - [Professionally conditioned pathology].
AB  - The existence of some differences between the indices of morbidity with temporary
      disablement in some working sectors in which do work persons having similar sex
      and age features determined the authors to adopt the term of professionally
      conditioned pathology for the affections in the etiology of which favouring
      factors of professional nature do interpose. In the modern society, as the
      manifest professional pathology is diminishing, the industrial medicine, as a
      scientific discipline, is changing its sphere and content, increasingly orienting
      itself towards the investigation of the professionally conditioned pathology and
      its implications in the medical practice. The prioritary orientation towards the
      prevalent diseases of the modern society is a main task for the present and
      future industrial medicine.

PMID- 25588252
TI  - [New parameters of electrocardiotachographic (EKT) evaluation of the
      organovegetative reactivity].
AB  - The analysis of some EKT lines evolution obtained by some investigations on the
      organovegetative reactivity carried out in the Laboratory of physiology
      correlated with the different experimental stages led to the formulation of some
      original cardiotachographic (KTG) parameters which seem to have a peculiar
      usefulness within the framework of the investigation methods. Except for the
      routine KTG parameters under the form of instantaneous cardiac rhythm (ICR) and
      mean cardiac rhythm (MCR) another 5 indices can now be used: 1) frequency of the
      rhythm fluctuations (FRF); 2) vegetative lability index (VLI); 3) mean rhythm
      fluctuation (MRF); 4) latency of rhythm fluctuation (LRF) and 5) amplitude of
      rhythm fluctuation (ARF). Their introduction as part of the investigation methods
      for the neurovegetative system would permit a better outline both of the relative
      relationship. between the component parts of the reactive system (normotonic or
      distonic) and its receptivity and promptitute to the different neurohumoral or
      somato-viscero-motor interferences.

PMID- 25588253
TI  - Mechanisms of the neuromuscular blocking activity of the aminoglycoside
      antibiotic streptomycin.
AB  - While increasing the spontaneous quantal transmitter release in frog
      neuromuscular junctions, streptomycin blocked the evoked transmitter release by
      decreasing the quantal content (m). The quantal parameter of release n (number of
      release sites) was significantly decreased, while p (probability of release
      through transmitter activation) increased. Streptomycin competes with calcium
      ions for the membrane release sites while the intracellular mechanisms of release
      remain unaffected. The data show a good fit to the two-step hypothesis of quantal
      transmitter release recently developed on the basis of ouabain actions.

PMID- 25588254
TI  - [Visceral arterial embolization (VAE). Note I. VAE in renal cancer. Experimental
      study and preliminary clinical results].
AB  - After a short history of the VAE, a new method in the intervention radiology, the
      authors present the technique and results of the experimental renal VAE performed
      on dogs, with autologous clot, Gelaspon and Isobutyl-2-cyanoacrylat. The
      favourable results of the experimental investigations permitted for the first
      time in our country the use of VAE in inoperable renal cancers. The paper
      presents the clinico-therapeutical results of VAE as well as the control
      angiographic and echotomographic aspects after embolization. The conclusions
      support the need of using VAE both preoperatively and in the inoperable cases of
      renal cancer, suggesting the possibility of extending the use of this method to
      other visceral cancers with selective arterial catheterizations approach.

PMID- 25588255
TI  - [Rotaviruses and their implications in pathology].

PMID- 25588256
TI  - [Considerations on the crown restoration in youngsters and teenagers].
AB  - The crown restorations in young people and teenagers represents a priority in the
      current dental practice. After presenting plurifactorially the etiology of the
      odontal lesions, the different methods of treatment employed currently in our
      clinic are analysed. In order to avoid some confusion in the use of some already
      accepted terms and to select the best treatment, the most common therapeutic
      means of crown restoration are described and analysed.

PMID- 25588257
TI  - [Some oral manifestations in blood disorders].
AB  - The authors present their own experience regarding the detection of hemopathies
      based upon the alterations of oral and tongue mucosae. The blood test confirmed
      the suspicion of hemopathy.

PMID- 25588258
TI  - [Digestive pathology in the elderly].
AB  - Some etiopathogenic, physiopathologic, clinic, evolutive and therapeutic
      peculiarities of the most common digestive affections encountered in the old aged
      patients are presented.

PMID- 25588259
TI  - [Is pain a symptom in placenta praevia?].

PMID- 25588260
TI  - [2-R-mercapto-1, 3, 4-thyadiazol derivates having biological activity. Note I].
AB  - The importance of 1,3,4-thyadiazol nucleus is illustrated by the fact that it
      enters the structure of many compounds having different biological activities. In
      this paper the results of some investigations for obtaining new derivates of
      1,3,4-thydiazol 2,5 distributed are presented. Based upon the presented diagram
      13 2-R-5-mercapto-1,3,4-thyadiazols, analysed both physico-chemically and
      biologically were synthetized.

PMID- 25588261
TI  - [Investigations for obtaining compounds with potential antiinflammatory action,
      carboxymethylic ethers of some oximes].
AB  - In this paper the synthesis of 5 etheric derivates of some aromatic oxymes: p
      metoxy-benz-(sin)-aldoxyme, p-chlorine-benz-(sin)-aldoxyme, sin-piperonal-oxyme,
      2,4-di- chlorinebenzaldoxyme and 3,4-dichlor-benzaldoxyme were described. In view
      of a subsequent study on the antiinflammatory action a simple method for
      obtaining these compounds based on the reaction between the sodium salt of the
      monochloracetic acid and the sodium derivates of the corresponding oxymes. The
      structure of the newly obtained products was confirmed by the elementary
      quantitative chemical analysis and the spectral analysis in IR.

PMID- 25588262
TI  - [Studies regarding the fixing of the zinc from ADH through some azopyrazolone].
AB  - The mechanism of reaction-between the zinc atom of alcohol dehydrogenase and 6
      pyrazolone and azopyrazolone compounds, type 1-(4'-carboxyphenyl)-3-methyl
      4(1"azo-4"-ethoxy-phenyl)-5-pyrazolone, synthetized by the authors, is studied.
      For elucidating the "in vivo" phenomenon, the complexes of these compounds were
      synthetized with zinc atoms, the IR specters and quantitative chemical analyses
      being followed. Based on these, the possibilities of complexing the zinc from the
      ADH molecule by these compounds are discussed.

PMID- 25588263
TI  - [Pharmacological trial of a glucose acetylate derivative].
AB  - Toxicological and pharmacokinetic data regarding a glucose acetylate derivative,
      conventionally termed PAG, are presented.

PMID- 25588264
TI  - [Recording of pH of the lower part of esophagus].

PMID- 25588266
TI  - [Surgical acute abdomen].

PMID- 25588265
TI  - [Aspects of progress in toxicology].

PMID- 25588267
TI  - [Medical acute abdomen].

PMID- 25588268
TI  - The influence of cyclooxygenase inhibitors on morphine addiction.

PMID- 25588269
TI  - [Possibilities and limitations in the surgical treatment of subdiaphragmatic
      digestive tract cancer].

PMID- 25588271
TI  - Detecting letters and words in prose passages: a test of alternative theoretical
      accounts of the missing letter effect.
AB  - College students searched for either h or the in prose passages in which every h
      occurred in the test word the. In Experiment 1, passage versions differed in that
      the critical noun phrases were either the alone (i.e., in citation form as a noun
      referring to itself) or "the definite article." Many more detection errors
      occurred for letter than word target items, especially with "the definite
      article." In Experiment 2, passage versions differed in that a given noun phrase
      containing the test word the occurred as a subject in one version and an object
      in the other. Again, many more detection errors occurred when the target item was
      the letter h than when it was the letter sequence the. Also, with letter but not
      letter sequence targets, more detection errors occurred for object than subject
      noun phrases. In Experiment 3, passages were presented either in regular format
      or with all capital letters. Students made more detection errors with the regular
      than with the capitals format, many more errors occurred when participants
      searched for letters than for letter sequences, and the effect of target item was
      larger with regular than with capitals format. These findings suggest that
      accounts of detection errors in reading must include the influence of unitization
      and processing time or attentional allocation.

PMID- 25588270
TI  - Improvements in perception of maximum reaching height transfer to increases or
      decreases in reaching ability.
AB  - Perception of affordances for a given behavior reflects not only a person's
      current action capabilities but also impending changes to his or her action
      capabilities. This experiment investigated perception of affordances for reaching
      when the means of performing the reaching task would increase or decrease
      reaching ability. The results showed that in both cases perception of maximum
      reaching height reflected the person's anthropometric properties (i.e., standing
      height) and the future means of reaching, and improvements in perception of
      maximum reaching height transferred to unpracticed reaching tasks. The results
      highlight the role of action in the perception of affordances and are discussed
      in the context of a description of perceptual systems as smart perceptual
      devices.

PMID- 25588272
TI  - A possible correction of the face inversion effect: a methodological commentary.
AB  - The face inversion effect is based on 2 phenomena: Recognition of faces presented
      upright (hair above, chin below) is better than that of faces presented inverted
      (chin above, hair below), and inversion impairs recognition of faces more than of
      nonfacial objects (buildings, cars). Based on theoretical and empirical
      considerations, this article suggests that in many cases the size of the second
      phenomenon is overestimated, because it is influenced by recognition of upright
      faces being higher than recognition of upright objects (i.e., a baseline-level
      effect). A mathematically based correction is suggested for the baseline-level
      effect. It rests on the assumption that recognition of inverted faces depends on
      recognition of upright faces. Theoretical and empirical support is offered for
      this assumption. Also, an empirical base for the proposed correction is provided.

PMID- 25588273
TI  - Effects of gender, imagery ability, and sports practice on the performance of a
      mental rotation task.
AB  - Mental rotation is one of the main spatial abilities necessary in the spatial
      transformation of mental images and the manipulation of spatial parameters.
      Researchers have shown that mental rotation abilities differ between populations
      depending on several variables. This study uses a mental rotation task to
      investigate effects of several factors on the spatial abilities of 277
      volunteers. The results demonstrate that high and low imagers performed equally
      well on this tasks. Athletes outperformed nonathletes regardless of their
      discipline, and athletes with greater expertise outperformed those with less
      experience. The results replicate the previously reported finding that men
      exhibit better spatial abilities than women. However, with high amounts of
      practice, the women in the current study were able to perform as well as men.

PMID- 25588274
TI  - Working memory, situation models, and synesthesia.
AB  - Research on language comprehension suggests a strong relationship between working
      memory span measures and language comprehension. However, there is also evidence
      that this relationship weakens at higher levels of comprehension, such as the
      situation model level. The current study explored this relationship by comparing
      10 grapheme-color synesthetes who have additional color experiences when they
      read words that begin with different letters and 48 normal controls on a number
      of tests of complex working memory capacity and processing at the situation model
      level. On all tests of working memory capacity, the synesthetes outperformed the
      controls. Importantly, there was no carryover benefit for the synesthetes for
      processing at the situation model level. This reinforces the idea that although
      some aspects of language comprehension are related to working memory span scores,
      this applies less directly to situation model levels. This suggests that theories
      of working memory must take into account this limitation, and the working memory
      processes that are involved in situation model construction and processing must
      be derived.

PMID- 25588275
TI  - The importance of source and cue type in time-based everyday prospective memory.
AB  - We examined the effects of the source of a prospective memory task (provided or
      generated) and the type of cue (specific or general) triggering that task in
      everyday settings. Participants were asked to complete both generated and
      experimenter-provided tasks and to send a text message when each task was
      completed. The cue/context for the to-be-completed tasks was either a specific
      time or a general deadline (time-based cue), and the cue/context for the texting
      task was the completion of the task itself (activity-based cue). Although
      generated tasks were completed more often, generated cues/contexts were no more
      effective than provided ones in triggering the intention. Furthermore, generated
      tasks were completed more often when the cue/context comprised a specific time,
      whereas provided tasks were completed more often when the cue/context comprised a
      general deadline. However, texting was unaffected by the source of the
      cue/context. Finally, emotion modulated the effects. Results are discussed within
      a process-driven framework.

PMID- 25588276
TI  - Monetary and affective judgments of consumer goods: modes of evaluation matter.
AB  - Participants who evaluated 2 positively valued items separately reported more
      positive attraction (using affective and monetary measures) than those who
      evaluated the same two items as a unit. In Experiments 1-3, this separate/unitary
      evaluation effect was obtained when participants evaluated products that they
      were purchasing for a friend. Similar findings were obtained in Experiments 4 and
      5 when we considered the amount participants were willing to spend to purchase
      insurance for items that they currently owned. The averaging/summation model was
      contrasted with several theoretical perspectives and implicated averaging and
      summation integration processes in how items are evaluated. The procedural and
      theoretical similarities and differences between this work and related research
      on unpacking, comparison processes, public goods, and price bundling are
      discussed. Overall, the results support the operation of integration processes
      and contribute to an understanding of how these processes influence the
      evaluation and valuation of private goods.

PMID- 25588277
TI  - Ethics under uncertainty: the morality and appropriateness of utilitarianism when
      outcomes are uncertain.
AB  - Real-life moral dilemmas inevitably involve uncertainty, yet research has not
      considered how uncertainty affects utilitarian moral judgments. In addition, even
      though moral dilemma researchers regularly ask respondents, "What is
      appropriate?" but interpret it to mean, "What is moral?," little research has
      examined whether a difference exists between asking these 2 types of questions.
      In this study, 140 college students read moral dilemmas that contained certain or
      uncertain consequences and then responded as to whether it was appropriate and
      whether it was moral to kill 1 to save many (a utilitarian choice). Ratings of
      the appropriateness and morality of the utilitarian choice were lower under
      uncertainty than certainty. A follow-up experiment found that these results could
      not be explained entirely by a change in the expected values of the outcomes or a
      desire to avoid the worst-case scenario. In addition, the utilitarian choice to
      kill 1 to save many was rated as more appropriate than moral. The results imply
      that moral decision making may depend critically on whether uncertainties in
      outcomes are admitted and whether people are asked about appropriateness or
      morality.

PMID- 25588278
TI  - Goals, styles, and decisions: changes and interactions during the first year of
      college.
AB  - First-year undergraduates participated in a short-term longitudinal study of goal
      setting and decision making over their first 14 months of college. First,
      students wrote a mission statement, listed their goals for the upcoming year, and
      filled out several individual difference style measures. In subsequent sessions,
      students were surveyed about different decisions pertaining to their choice of
      college major, course selection, housing, and summer plans. At the beginning of
      their second year, participants were shown their previously listed goals and
      surveyed about their progress, their satisfaction with their progress, and their
      retrospective view of their goals. Additionally, participants responded again to
      the individual difference measures. A moderate degree of stability was found in
      the individual difference measures, yet there were several significant changes
      over the year. Goal evaluation scores correlated with specific individual
      difference measures, and self-reported descriptions of reactions to how specific
      decisions were made, but not with behavioral measures of decision making.We
      speculate on ways in which stylistic measures become part of a construction of a
      more general narrative identity, shaped in significant ways by the college
      environment that selectively reinforces some analytic habits of mind.

PMID- 25588279
TI  - Identifying at-risk drinkers in primary care.

PMID- 25588280
TI  - Improving outcomes for chronic pain in primary care.
AB  - Although the patient's goal is often complete pain relief, this is rarely a
      realistic outcome, so the role of the physician in managing chronic pain involves
      optimising pain relief as far as possible. Careful explanation and education may
      be needed to enable the focus to shift from cure to better management of pain,
      and improvement of function and quality of life. Chronic pain is defined as pain
      continuing beyond the normal time for tissue healing. Pain may be broadly
      classified on the basis of mechanism, as neuropathic, nociceptive or mixed. A
      thorough biopsychosocial assessment is essential so that an individualised
      multidisciplinary approach to management can be developed. The aims of assessment
      of chronic pain are to rule out any underlying serious pathology, identify the
      pain mechanism and identify and evaluate risk factors that contribute to
      chronicity. SIGN emphasises the need for a multidisciplinary team approach to
      improve outcomes, and highlights five broad categories of care: supported self
      management, drug treatment, psychologically-based interventions, physical
      therapies and complementary therapies. Exercise, regardless of its type and the
      source of pain, is recommended for the management of chronic pain. In chronic low
      back pain, exercise therapy can improve strength and range of motion across
      joints, cardiorespiratory fitness and sense of wellbeing. Pain management
      programmes reduce anxiety and depressive symptoms, increase function and improve
      mood. They may be considered in patients with poor functional capacity, pain
      related social and occupational problems and in cases where other management
      strategies have failed.

PMID- 25588281
TI  - Migraine is underdiagnosed and undertreated.
AB  - Migraine is a common neurovascular disorder characterised by attacks of head pain
      that are typically unilateral and often described as severe and throbbing in
      association with nausea and sensitivity to sensory input, i.e. light, sound and
      head movement. The headaches typically last 4-72 hours, up to 31% of migraineurs
      have aura on some occasions. Migraine is commonly episodic. With an increasing
      intake of painkillers, patients often complain of an escalation of migraine
      attacks or a transformation to a chronic daily background pain with
      exacerbations. Acute painkiller use, both prescription and OTC, should be
      enquired about in all cases and medication overuse headache suspected and managed
      if patients are taking any acute painkiller excessively. Migraineurs should be
      encouraged to have regular habits. Regular sleep, exercise, meals, work habits
      and relaxation will be rewarded by a reduction in headache frequency. NICE
      guidelines recommend adopting the stepped-down approach to management. They
      suggest a combination of a triptan, NSAID or paracetamol, and an anti-emetic
      taken as early as possible during the headache. The decision to commence a
      preventative agent should depend on a combination of attack frequency, duration
      and severity, as well as response to abortive therapy and patient preference.

PMID- 25588282
TI  - Preventing avoidable asthma deaths.
AB  - The UK has one of the highest death rates in Europe from asthma, with more than
      20 people dying from the disease each week. Across the UK there is a five-fold
      variation in the number of hospital admissions for asthma almost certainly
      explained in part by variations in delivery, uptake and organisation of care.
      Deaths from asthma are frequently avoidable the findings from the National Review
      of Asthma Deaths have confirmed. A total of 276 cases were considered by the
      confidential enquiry panels and 195 confirmed as asthma deaths. Major avoidable
      factors were judged to be present in 60% of cases. Key findings from the report
      include: Almost half the patients (45%) died without seeking medical help or
      before help could be provided; 10% died within 28 days of discharge from
      hospital; 21% had attended A&E with asthma in the previous year; and only 23% had
      a personal asthma action plan. Over-prescription of short-acting bronchodilators
      and under-prescription of preventer inhalers was common. Every general practice
      should have a designated, named clinical lead for asthma services. Patients with
      asthma should be referred to a specialist asthma service if they have required
      more than two courses of systemic corticosteroids, oral or injected, in the
      previous 12 months or management using BTS steps 4 or 5 to achieve control. Any
      patient admitted to hospital or attending A&E with asthma should be reviewed, and
      control optimised, within a week of discharge. All asthma patients should have a
      written personal asthma action plan and should have a structured review by a
      healthcare professional with training. in asthma at least annually.

PMID- 25588283
TI  - Conditions in children.

PMID- 25588285
TI  - The changing face of general practice.

PMID- 25588284
TI  - Autotherapy in the prevention and cure of purulent infections. 1914.

PMID- 25588286
TI  - Neuroimaging of Ethiopian patients with epilepsy: a retrospective review.
AB  - BACKGROUND: Epilepsy is arguably the most common neurological condition
      encountered by neurologists in Africa. Neuroimaging (CT and MRI) represents the
      most important recent contribution to the diagnosis, classification and
      management of the patient with epilepsy. OBJECTIVE: To describe the role of
      neuroimaging in the evaluation of Ethiopian patients with epilepsy, by
      identifying intracranial pathology, and formulating syndromic and etiological
      diagnoses. METHODS: We performed a retrospective review of neuroimaging in 181
      patients with epilepsy presenting to a specialized referral hospital (Addis Ababa
      University Tikur Anbessa Teaching Hospital) and a private clinic (Yehuleshet
      Higher Clinic) in Addis Ababa, Ethiopia between September 2008 and August 2010.
      Each patient had an interictal EEG recording. RESULTS: Neuroimaging demonstrated
      abnormal intracranial structural lesions in 65 of 181 or 35.9% of epileptic
      patients (31% with CT; 38% with MRI). Brain lesions were single in 28 (42.8%) and
      multiple in 23 (35.4%) patients. The lesions were lateralized in 35 patients
      (53.8%), with 23 (35.4%) on the left add 12 (18.5%) on the right. Twenty seven
      (41.5%) of these lesions originated in or involved the temporal or frontal lobes.
      Over one third of the lesions were lobar equally divided among temporal, frontal
      and parietal regions. The imaging findings demonstrated intracranial space
      occupying lesions (ICSOL) in 17 (9.4%) patients (with 64.7% brain tumors),
      cerebral infarctions in 15 (8.3%), cortical atrophy in 9 (5.0%), and gliosis in
      7(3.9%). The interictal EEG recordings revealed epileptiform abnormalities in
      60/181 patients (33.1%). CONCLUSION: Neuroimaging detected intracranial pathology
      in more than one third of Ethiopian patients with epilepsy. A significant
      proportion of the cases demonstrated focal epileptiform discharges and non
      epileptiform features with abnormal intracranial pathologies. Further prospective
      neuroimaging studies are recommended. Brain scan and EEG did help in the
      diagnosis, classification and treatment of epileptics.

PMID- 25588287
TI  - Microscopic transphneoidal surgery experence from christian Medical Center Addis
      Abeba Ethiopia.
AB  - BACKGROUND: The transphneoidal approach to the pituitary gland using the
      microscope has undergone continuous modification since its introduction by Hardy
      over 50 years ago. It is one of the most effective and safest of major
      neurosurgical procedures with excellent outcomes and low complication rates.
      OBJECTIVE: To describe the experience of Endonasal microscopic transsphenoidal
      surgery at Myungsung Christian Medical Center during three-years period. PATIENTS
      AND METHODS: This is a hospital based retrospective review of patients with
      pituitary tumor for whom microscopic transsphenoidal surgery was done in
      Myungsung Christian Medical Center, Addis Ababa, Ethiopia in the period between
      September 2010 and August 2014. Patients' demographic data, type of symptoms,
      hormonal profile, imaging modality, complications and outcomes were recorded in
      apre-formed questionnaire. Frequencies and means were computed for description of
      the various variables and presented in prose form and graphs. The association
      between categorical variables was calculated using Chi-square test. RESULTS:
      sixteen (53.3%) patients were males, 14 (46.7%) females. The mean age was 33.77,
      +/- 10.85 years (rang 14 - 53). The most common presentation were headache in 28
      (93.3%) patients and visual disturbances in 26 (86.7%), while 18 (60%) had
      bitemporal hemianopia. prolactin levels were elevated in 4 (13.3%) of them having
      hyperprolactinemia, cortisol levels revealed hypercortisolemia with clinical
      evidence Cushing disease in 5 (16.7%). Three ((10%) had elevated growth hormone
      levels with acromegalic features. All patients included in the study had a MRI;
      tumors were with suprasellar extension in all (100%) patients, involvement of
      floor ofsella in 18 (60%), extension to sphenoid sinus in 8 (26.7%) and with
      parasellar extension in 5 (16.7%). Twenty-seven (90%) were done through direct
      transnasal, 2 (6.7%) transseptal transphneoidal approach; in one patient the
      approach was translabial. Early complication and mortality rate was 18 (60%) and
      2 (6.7%) respectively. At one-year follow-up period, 22 (73.3%) patients had good
      functional outcome, while 6 (20% 0 were in the same status as in the preoperative
      period, 2(6.7%) had residual/recurrent tumor. CONCLUSION: Our patients were
      relatively advanced cases with suprasellar and parasellar extensions. Direct
      transnasal approach, is straightforward, quick and does not require dissection of
      nasal mucosa or removal of septal cartilage and that the procedure can be done by
      neurosurgeon with some experience in the procedure without an increased risk of
      complications. High early complication rate was tolerable and manageable.
      Acceptable mortality and good functional outcome during follow up period is
      encouraging and compares favorably with African and other similar studies.

PMID- 25588288
TI  - Review of morbidity and mortality among patients adimitted to the Surgical
      Intensive Care Unit at Tikur Anbessa Specialized Teaching Hospital, Ethiopia.
AB  - BACKGROUND: Caring for the critically ill is a challenge in developing country
      including Ethiopia, where heath needs often outstrip available resources. There
      is scarce data available on morbidity and mortality of surgical intensive care
      unit patients in Ethiopia. OBJECTIVE: To describe mortality, morbidity and
      outcomes of patients under the care of surgical intensive care unit team between
      September 2010 and August 2011. PATIENTS AND METHODS: This is a hospital based
      retrospective review of morbidity and mortality among surgical patients admitted
      to Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia in the period
      between September 2010 and August 2011. RESULTS: The study reviewed 441 surgical
      intensive care unit admissions over one- year period Age ranged from 10 to 90
      years mean 37.55 +/- 16.56 years. Mortality was high in 21-30 years age group,
      9.1%. The highest admission was from cardiothoracic surgery unit, 37.4%, the
      average length of hospital stay was 4.52 days (range 1 to 87 days). Significant
      number 52 (33.3%) of patients who died under surgical ICU care belongs to General
      surgery unit. Two Hundred eighty (63.5%) patients had an uneventful course, while
      156 (35.4%) and 161 (36.5%) died and developed complications respectively. Age of
      the patient at the time of admission, mode of admission, and post admission
      complications were significantly and positively associated with mortality (p =
      0.0001) while gender did not show any association with mortality at SICU (p =
      0.528).CCONCLUSION:The highest admission was from department of cardiothoracic
      surgery, while mortality rate was high-st from general surgery side. There are
      significant and positive associations ofa ge, urgency ofa dmission, and
      complications with mortality while gender did not show any association.

PMID- 25588289
TI  - Tuberculosis of the cervix mimicking cervical cancer.
AB  - Tuberculosis of the cervix is a rare disease and accounts for 0.1-0.65% of all
      cases of tuberculosis. We present an unusual case of a 57 years old female who
      presented with chief complaints of Serosaguineous vaginal discharge of one year
      duration and irregular firm cervix with contact bleeding and was clinically
      diagnosed to have cervical cancer. Histopathology revealed typical findings of
      cervical tuberculosis. Cervical tuberculosis should be considered as a
      differential diagnosis of cervical malignancy. The clinical presentation and
      diagnosis of cervical tuberculosis is reviewed.

PMID- 25588290
TI  - Adrenocortical carcinoma in a 3% years old girl with hetro-sexual precocity.
AB  - Adrenocortical carcinoma is a rare neoplasm in children. Hetro-sexual precocious
      puberty could be the initial presentation of a rare adrenocortical neoplasm in
      the pediatric age group. Features of hetro-sexual precocious puberty in a girl
      should alert the possibility of such a rare disease. We report a rare case of
      adrenocortical carcinoma in a three years and six months old girl who presented
      with hetro-sexual precocious puberty of two years duration. Left adrenalectomy
      was done and histopathology revealed adrenocortical carcinoma.

PMID- 25588291
TI  - Parosteal lipoma with hyperostosis: case report.
AB  - Parosteal lipoma is an extremely rare benign tumor that is composed mainly of
      mature adipose tissue and has an intimate relationship to the underlying
      periosteal bone. We present a case of parosteal lipoma of humerus combined with
      hyperostosis. Standard radiography demonstrated a radiolucent mass surrounding an
      exostosis. CT showed a fat density, lobulated mass surrounding the larger osseous
      excrescence and cortex. The patient underwent surgery. Intraoperative examination
      found a well encapsulated, homogenous, yellowish, fatty tissue attached by a
      stalk to the underlying bone. The pathology specimen showed mature adipose tissue
      consistent with the intraoperative finding.

PMID- 25588292
TI  - Severe hospital acquired pneumonia and septicemia due TO methicillin resistant
      Staphylococcus lugdunensis in a newborn in Northwestern Ethiopia.
AB  - Staphylococcus lugdunensis can cause virulent infections in immunosuppressed
      individuals. This report describes the first known case of hospital acquired
      pneumonia and septicemia due to methicillin-resistant Staphylococcus lugdunensis
      in a newborn at Felege Hiwot Referral Hospital, North Western Ethiopia. The
      strain was simultaneously resistant to trimethoprim-sulfamethoxazole,
      tetracycline (30 ug), chloramphenicol (30 ug), gentamycin (10ug) and
      ciprofloxacin (5ug) but sensitive to erythromycin (15ug) and clindamycin (10ug).

PMID- 25588293
TI  - Importance of national context in the translation of personalised treatments for
      smoking cessation.

PMID- 25588295
TI  - Electrophysiologic characteristics of ventricular arrhythmias arising from the
      aortic mitral continuity - potential role of the conduction system.

PMID- 25588296
TI  - Effects of huwentoxin-I on catecholamines in cultured PC12 cells.
AB  - The measurement of catecholamines in biological samples remains a current
      analytical challenge in the study on neurotransmitter release, although much
      effort has been devoted toward the relevant methodology. Here we first
      established a fluoresence-based method for the quantitative determination of
      catecholamines and then applied it to the investigation of effects of huwentoxin
      I (HWTX-I), a peptide neurotoxin, on catecholamines in cultured PC12 cells. The
      results showed that treatment with HWTX-I at different concentrations (10, 50,
      100 and 1000 nM) for 20 min significantly increased dopamine (DA) content in the
      culture medium (p < 0.01), with ~1.6-fold increase compared with that of the
      control at the highest concentration tested. Within 20 min, DA content in the
      medium increased with increasing the treatment time. In contrast, HWTX-I
      decreased norepinephrine (NE) content in the medium. However, after the PC12
      cells were treated with HWTX-I, the intracellular contents of both DA and NE were
      kept at a relatively constant level. These data suggest that HWTX-I
      differentially affects the DA and NE of the neuroendocrine cells, with enhancing
      the actions of DA and weakening those of NE.

PMID- 25588297
TI  - Feature confirmation in object perception: Feature integration theory 26 years on
      from the Treisman Bartlett lecture.
AB  - The Treisman Bartlett lecture, reported in the Quarterly Journal of Experimental
      Psychology in 1988, provided a major overview of the feature integration theory
      of attention. This has continued to be a dominant account of human visual
      attention to this day. The current paper provides a summary of the work reported
      in the lecture and an update on critical aspects of the theory as applied to
      visual object perception. The paper highlights the emergence of findings that
      pose significant challenges to the theory and which suggest that revisions are
      required that allow for (a) several rather than a single form of feature
      integration, (b) some forms of feature integration to operate preattentively, (c)
      stored knowledge about single objects and interactions between objects to
      modulate perceptual integration, (d) the application of feature-based inhibition
      to object files where visual features are specified, which generates feature
      based spreading suppression and scene segmentation, and (e) a role for attention
      in feature confirmation rather than feature integration in visual selection. A
      feature confirmation account of attention in object perception is outlined. 

PMID- 25588294
TI  - Use of the nicotine metabolite ratio as a genetically informed biomarker of
      response to nicotine patch or varenicline for smoking cessation: a randomised,
      double-blind placebo-controlled trial.
AB  - BACKGROUND: Substantial variability exists in therapeutic response and adverse
      effects with pharmacotherapies for tobacco dependence. Biomarkers to optimise
      treatment choice for individual smokers might improve treatment outcomes. We
      tested whether a genetically informed biomarker of nicotine clearance, the
      nicotine metabolite ratio (NMR; 3'-hydroxycotinine:cotinine), predicts response
      to nicotine patch or varenicline for smoking cessation. METHODS: We undertook NMR
      stratified multicentre, randomised, placebo-controlled clinical trial from Nov
      16, 2010, to Sept 12, 2014, at four sites. Smokers seeking treatment were
      randomly assigned by baseline NMR status and study site, in blocks of 12 patients
      (1:1:1 ratio), to 11 weeks of placebo (placebo pill plus placebo patch), nicotine
      patch (active patch plus placebo pill), or varenicline (active pill plus placebo
      patch), plus behavioural counselling. Participants and investigators were masked
      to group allocation and NMR status. An intention-to-treat analysis was done.
      Participants were followed up for 12 months after the target quit date. The
      primary endpoint was biochemically verified 7 day point prevalence abstinence at
      the end of treatment to estimate the pharmacological effect of treatment by NMR.
      The trial is registered at ClinicalTrials.gov, number NCT01314001. FINDINGS: 1246
      participants (662 slow metabolisers of nicotine, 584 normal metabolisers of
      nicotine) were enrolled and randomly assigned to the three interventions (408
      placebo, 418 nicotine patch, 420 varenicline). At end of treatment, varenicline
      was more efficacious than nicotine patch in normal metabolisers (OR 2.17, 95% CI
      1.38-3.42; p=0.001), but not in slow metabolisers (OR 1.13, 0.74-1.71; p=0.56).
      In the longitudinal model including all timepoints, the NMR-by-treatment
      interaction was significant (ratio of odds ratios [ORR] 1.96, 95% CI 1.11-3.46;
      p=0.02). An NMR-by-treatment interaction showed that slow (vs normal)
      metabolisers reported greater overall side-effect severity with varenicline
      versus placebo (beta=-1.06, 95% CI -2.08 to -0.03; p=0.044). INTERPRETATION:
      Treating normal metabolisers with varenicline and slow metabolisers with nicotine
      patch could optimise quit rates while minimising side-effects. FUNDING: National
      Institutes of Health, Canadian Institutes of Health Research, Abramson Cancer
      Center, Centre for Addiction and Mental Health Foundation, and Pennsylvania
      Department of Health.

PMID- 25588298
TI  - Editorial Note to the last issue of Hereditas.

PMID- 25588299
TI  - A tale of two papers.
AB  - Two papers published in HEREDITAS between 1921 and 1939 show how the attitude
      towards race biology changed in the course of the interwar period in the Nordic
      countries. In the early 1920s race biology was seen to constitute a legitimate
      science. Ordinary human genetics prevailed, however, over race biology already in
      the very beginning on the pages of HEREDITAS. Population thinking was introduced
      into the study of human heredity around the year 1930. It effectively
      contradicted the concept of the race. Interestingly, HEREDITAS does not carry a
      single paper on eugenics and sterilization. In 1939 we see a final repudiation of
      the doctrines on race. Times had changed and the National Socialists had usurped
      the doctrines of race in Germany. 

PMID- 25588300
TI  - Strange history: the fall of Rome explained in Hereditas.
AB  - In 1921 Hereditas published an article on the fall of Rome written by the famous
      classical scholar Martin P:son Nilsson. Why was a paper on this unexpected topic
      printed in the newly founded journal? To Nilsson, the demise of the Roman Empire
      was explained by the "bastardization" occurring between "races" from different
      parts of the realm. Offspring from mixed couples were of a less stable "type"
      than their parents, due to the breaking up by recombination of the original
      hereditary dispositions, which led to a general loss of competence to rule and
      govern. Thus, the "hardness" of human genes, together with their recombination,
      was - according to Nilsson - the main cause of the fall of Rome. Nilsson's
      argument is not particularly convincingly presented. Human "races" are taken to
      have the same genetic structure as inbred crop strains, and Nilsson believes in a
      metaphysical unity between the individual and the race to which it belongs.
      However, in my view, Martin P:son Nilsson and his friend Herman Nilsson-Ehle had
      wider aims with the article than to explain a historical event. The article can
      be read as indicating strong support from the classical human sciences to the
      ambitious new science of genetics. Support is also transferred from genetics to
      the conservative worldview, where the immutability and inflexibility of the
      Mendelian genes are used to strengthen the wish for greater stability in politics
      and life. The strange article in Hereditas can, thus, be read as an early
      instance in the - still ongoing - tug-of-war between the conservative and the
      liberal ideological poles over how genetic results best are socially interpreted.

PMID- 25588301
TI  - Association analysis of the GRM8 gene with schizophrenia in the Uygur Chinese
      population.
AB  - GRM8 is a schizophrenia candidate gene that is also thought to be involved in the
      glutamate pathway, which is very important in the pathogenesis of schizophrenia.
      In this study, we aim to investigate the association between GRM8 and
      schizophrenia in the Uygur Chinese population. Rs2237748 and rs2299472, located
      in the GRM8 gene, were selected for genotyping in a set of Uygur Chinese case
      control samples, which included 723 cases and 561 controls, using TaqMan assays
      and capillary sequencing. The statistical analysis was carried out using the
      online software program SHEsis, and a meta-analysis was carried out to identify
      other relevant studies using Review Manager 5. We found that the rs2299472
      genotype was significantly associated with schizophrenia (P = 0.015, P = 0.030,
      after Bonferroni correction). The frequency of the CC genotype was higher in the
      schizophrenic patients (P = 0.008), and the frequency of the AC genotype was
      lower (P = 0.008). Furthermore, the meta-analysis incorporating the previous and
      current studies also showed that rs2299472 is associated with schizophrenia. This
      study indicates that the GRM8 gene may play an important role in the pathogenesis
      of schizophrenia. 

PMID- 25588302
TI  - Genetic diversity and population structure of leafy kale and Brassica rupestris
      Raf. in south Italy.
AB  - Local varieties of leafy kales (Brassica oleracea L.) are grown in home gardens
      in Calabria and Sicily for self-consumption, in the same area where the wild
      relative Brassica rupestris Raf. also grows. With the use of AFLP markers,
      comparisons were made of the genetic diversity and population structure of ten
      wild and 22 cultivated populations, as well as of a hybrid population and of four
      commercial cultivars of different B. oleracea crops. The level of genetic
      diversity was higher in leafy kales than in wild populations and this diversity
      was mainly distributed within populations. Wild populations remained distinct
      from cultivated material. Additionally, most wild populations were distinctively
      isolated from each other. On the other hand, it was not possible to molecularly
      distinguish even geographically distant leafy kale populations from each other or
      from different B. oleracea crops. It was possible to detect inter-crossing
      between leafy kales and B. rupestris. Findings from this study illustrate the
      existing level of genetic diversity in the B. oleracea gene pool. Individual
      populations (either wild or leafy kales) with higher levels of genetic diversity
      have been identified and suggestions are given for an informed conservation
      strategy. Domestication hypotheses are also discussed. 

PMID- 25588303
TI  - Deletion mapping in the Enhancer of split complex.
AB  - The Enhancer of split complex [E(spl)-C] comprises twelve genes of different
      classes. Seven genes encode proteins of with a basic-helix-loop-helix-orange
      (bHLH-O) domain that function as transcriptional repressors and serve as
      effectors of the Notch signalling pathway. They have been named E(spl)m8-, m7-,
      m5-, m3-, mbeta-, mgamma- and mdelta-HLH. Four genes, E(spl)m6-, m4-, m2- and
      malpha-BFM are intermingled and encode Notch repressor proteins of the Bearded
      family (BFM). The complex is split by a single gene of unrelated function,
      encoding a Kazal-type protease inhibitor (Kaz-m1). All members within a family,
      bHLH-O or BFM, are very similar in structure and in function. In an attempt to
      generate specific mutants, we have mobilised P-element constructs residing next
      to E(spl)m7-HLH and E(spl)mgamma-HLH, respectively. The resulting deletions were
      mapped molecularly and by cytology. Two small deletions affected only E(spl)m7
      HLH and E(spl)mdelta. The deficient flies were viable without apparent phenotype.
      Larger deletions, generated also by X-ray mutagenesis, uncover most of the E(spl)
      C. The phenotypes of homozygous deficient embryos were analysed to characterize
      the respective loss of Notch signalling activity. 

PMID- 25588304
TI  - Wild Estonian and Russian sea trout (Salmo trutta) in Finnish coastal sea trout
      catches: results of genetic mixed-stock analysis.
AB  - For responsible fisheries management of threatened species, it is essential to
      know the composition of catches and the extent to which fisheries exploit weak
      wild populations. The threatened Estonian, Finnish and Russian sea trout
      populations in the Gulf of Finland are targets of mixed-stock fisheries. The fish
      may originate from rivers with varying production capacities, from different
      countries, and they may also have either a wild or hatchery origin. In order to
      resolve the composition of Finnish coastal sea trout catches, we created a
      standardized baseline dataset of 15 DNA microsatellite loci for 59 sea trout
      populations around the Gulf of Finland and tested its resolution for mixed-stock
      analysis of 1372 captured fish. The baseline dataset provided sufficient
      resolution for reliable mixture analysis at regional group level, and also for
      most of the individual rivers stocks. The majority (76-80%) of the total catch
      originated from Finnish sea trout populations, 6-9% came from Russian and 12-15%
      from Estonian populations. Nearly all Finnish trout in the catch were of hatchery
      origin, while the Russian and Estonian trout were mostly of wild origin. The
      proportion of fish in the Finnish catches that originated from rivers with
      natural production was at least one fifth (22%, 19-23%). Two different spotting
      patterns were observed among the captured trout, with a small and sparsely
      spotted form being markedly more common among individuals of Russian (28%) and
      Estonian origin (22%) than among fish assigned to a Finnish origin (0.7%). 

PMID- 25588305
TI  - An improved MALDI-TOF mass spectrometry procedure and a novel DNA marker for
      identifying over-expressed Bx7 glutenin protein subunit in wheat.
AB  - Wheat bread-making quality is mainly determined by glutenin proteins in the
      grain, which exist in a wide range of variable alleles with differential
      influence on processing attributes. A recently identified allele, Bx7 over
      expression (Bx7(oe) ), has been showing highly significant positive effects on
      wheat dough strength over the normally expressed Bx7 allele. SDS-PAGE and normal
      RP-HPLC procedures failed to separate the two alleles. In the current study, an
      extensively optimised MALDI-TOF based procedure and a refined DNA based marker
      for efficiently differentiating Bx7(oe) from normal Bx7 allele were established.
      Results indicated that the MALDI-TOF procedure is cost effective, high
      throughput, and proven reliable, while the refined PCR marker only amplifies
      Bx7(oe) allele, a clear advantage over the previously developed codominant
      marker. 

PMID- 25588306
TI  - Genetic polymorphism of 15 Y chromosomal STR loci and haplotypes of Henan Han
      population.
AB  - We studied and established a DNA database of 15 Y-STRs (DYS438, DYS446, DYS391,
      DYS390, DYS458, DYS534, DYS426, DYS626, DYS504, DYS505, DYS576, DYS532, DYS594,
      DYS522, DYS540) in a population sample of 102 unrelated, healthy, male
      individuals of Henan Han population. Allelic frequencies and statistical
      parameters of Han population were calculated. Totally 90 alleles were observed,
      with the corresponding allelic frequencies ranging from 0.0098 to 0.9020. 102
      haplotypes were found in the studied group, the haplotype diversity for 15 Y-STR
      loci was 1. The results of present study were valuable for human identification
      and paternity tests routine forensic applications in the region. 

PMID- 25588307
TI  - Analysis of the interaction between human RITA and Drosophila Suppressor of
      Hairless.
AB  - Notch signalling mediates intercellular communication, which is effected by the
      transcription factor CSL, an acronym for vertebrate CBF1/RBP-J, Drosophila
      Suppressor of Hairless [Su(H)] and C. elegans Lag1. Nuclear import of CBF1/RBP-J
      depends on co-activators and co-repressors, whereas the export relies on RITA.
      RITA is a tubulin and CBF1/RBP-J binding protein acting as a negative regulator
      of Notch signalling in vertebrates. RITA protein is highly conserved in
      eumatazoa, but no Drosophila homologue was yet identified. In this work, the
      activity of human RITA in the fly was addressed. To this end, we generated
      transgenic flies that allow a tissue specific induction of human RITA, which was
      demonstrated by Western blotting and in fly tissues. Unexpectedly, overexpression
      of RITA during fly development had little phenotypic consequences, even when
      overexpressed simultaneously with either Su(H) or the Notch antagonist Hairless.
      We demonstrate the in vivo binding of human RITA to Su(H) and to tubulin by co
      immune precipitation. Moreover, RITA and tubulin co-localized to some degree in
      several Drosophila tissues. Overall our data show that human RITA, albeit binding
      to Drosophila Su(H) and tubulin, cannot influence the Notch signalling pathway in
      the fly, suggesting that a nuclear export mechanism of Su(H), if existent in
      Drosophila, does not depend on RITA. 

PMID- 25588308
TI  - Identification of fruit related microRNAs in cucumber (Cucumis sativus L.) using
      high-throughput sequencing technology.
AB  - MicroRNAs (miRNAs) are approximately 21 nt noncoding RNAs that influence the
      phenotypes of different species through the post-transcriptional regulation of
      gene expression. Although many miRNAs have been identified in a few model plants,
      less is known about miRNAs specific to cucumber (Cucumis sativus L.). In this
      study, two libraries of cucumber RNA, one based on fruit samples and another
      based on mixed samples from leaves, stems, and roots, were prepared for deep
      sequencing. A total of 110 sequences were matched to known miRNAs in 47 families,
      while 56 sequences in 46 families are newly identified in cucumber. Of these, 77
      known and 44 new miRNAs were differentially expressed, with a fold-change of at
      least 2 and p-value < 0.05. In addition, we predicted the potential targets of
      known and new miRNAs. The identification and characterization of known and new
      miRNAs will enable us to better understand the role of these miRNAs in the
      formation of cucumber fruit. 

PMID- 25588309
TI  - Relatedness and diversity of nine Swedish local chicken breeds as indicated by
      the mtDNA D-loop.
AB  - In this study part of the mitochondrial D-loop was sequenced in a total of 40
      samples from nine Swedish local chicken breeds. Among our 40 samples we observed
      15 segregating sites and seven different haplotypes. The most common haplotype
      was present in all investigated individuals in five breeds and together with
      other haplotypes in three breeds. This haplotype is common in domestic chickens
      and has been found in both local and commercial breeds in many parts of the
      world. The breed Olandshona was most different from the other Swedish breeds with
      all three individuals sharing a haplotype that differed from the most common
      haplotype at nine of the 15 segregating sites. 

PMID- 25588311
TI  - Retrospective study of the prevalence of Pseudoloma neurophilia shows male sex
      bias in zebrafish Danio rerio (Hamilton-Buchanan).

PMID- 25588312
TI  - Ionic interaction of positive amino acid residues of fungal hydrophobin RolA with
      acidic amino acid residues of cutinase CutL1.
AB  - Hydrophobins are amphipathic proteins secreted by filamentous fungi. When the
      industrial fungus Aspergillus oryzae is grown in a liquid medium containing the
      polyester polybutylene succinate co-adipate (PBSA), it produces RolA, a
      hydrophobin, and CutL1, a PBSA-degrading cutinase. Secreted RolA attaches to the
      surface of the PBSA particles and recruits CutL1, which then condenses on the
      particles and stimulates the hydrolysis of PBSA. Here, we identified amino acid
      residues that are required for the RolA-CutL1 interaction by using site-directed
      mutagenesis. We quantitatively analyzed kinetic profiles of the interactions
      between RolA variants and CutL1 variants by using a quartz crystal microbalance
      (QCM). The QCM analyses revealed that Asp142, Asp171 and Glu31, located on the
      hydrophilic molecular surface of CutL1, and His32 and Lys34, located in the N
      terminus of RolA, play crucial roles in the RolA-CutL1 interaction via ionic
      interactions. RolA immobilized on a QCM electrode strongly interacted with CutL1
      (K(D)  = 6.5 nM); however, RolA with CutL1 variants, or RolA variants with CutL1,
      showed markedly larger KD values, particularly in the interaction between the
      double variant RolA-H32S/K34S and the triple variant CutL1-E31S/D142S/D171S (K(D)
      = 78.0 nM). We discuss a molecular prototype model of hydrophobin-based enzyme
      recruitment at the solid-water interface.

PMID- 25588313
TI  - A call for better reporting of conservation research data for use in meta
      analyses.

PMID- 25588310
TI  - Differences in the distribution, phenotype and gene expression of subretinal
      microglia/macrophages in C57BL/6N (Crb1 rd8/rd8) versus C57BL6/J (Crb1 wt/wt)
      mice.
AB  - BACKGROUND: Microglia/macrophages (MG/MPhi) are found in the subretinal space in
      both mice and humans. Our goal was to study the spatial and temporal
      distribution, the phenotype, and gene expression of subretinal MG/MPhi in mice
      with normal retinas and compare them to mice with known retinal pathology.
      METHODS: We studied C57BL/6 mice with (C57BL/6N), or without (C57BL/6J) the rd8
      mutation in the Crb1 gene (which, in the presence of yet unidentified
      permissive/modifying genes, leads to a retinal degeneration), and documented
      their fundus appearance and the change with aging. Immunostaining of retinal
      pigment epithelium (RPE) flat mounts was done for 1) Ionized calcium binding
      adaptor (Iba)-1, 2) FcgammaIII/II Receptor (CD16/CD32, abbreviated as CD16), and
      3) Macrophage mannose receptor (MMR). Reverse-transcription quantitative PCR (RT
      qPCR) was done for genes involved in oxidative stress, complement activation and
      inflammation. RESULTS: The number of yellow fundus spots correlated highly with
      subretinal Iba-1+ cells. The total number of subretinal MG/MPhi increased with
      age in the rd8 mutant mice, but not in the wild-type (WT) mice. There was a
      centripetal shift in the distribution of the subretinal MG/MPhi with age. Old rd8
      mutant mice had a greater number of CD16+ MG/MPhi. CD16+ cells had morphological
      signs of activation, and this was most prominent in old rd8 mutant mice (P < 1 *
      10(-8) versus old WT mice). Subretinal MG/MPhi in rd8 mutant mice also expressed
      iNOS and MHC-II, and had ultrastructural signs of activation. Finally, rd8 mutant
      mouse RPE/ MG/MPhi RNA isolates showed an upregulation of Ccl2, CFB, C3, NF
      kbeta, CD200R and TNF-alpha. The retinas of rd8 mutant mice showed upregulation
      of HO-1, C1q, C4, and Nrf-2. CONCLUSIONS: When compared to C57BL/6J mice,
      C57BL/6N mice demonstrate increased accumulation of subretinal MG/MPhi,
      displaying phenotypical, morphological, and gene-expression characteristics
      consistent with a pro-inflammatory shift. These changes become more prominent
      with aging and are likely due to the combination of the rd8 mutation and yet
      unidentified permissive/modulatory genes in the C57BL/6N mice. In contrast, aging
      leads to a scavenging phenotype in the C57BL/6J subretinal microglia/macrophages.

PMID- 25588314
TI  - Using text mining for study identification in systematic reviews: a systematic
      review of current approaches.
AB  - BACKGROUND: The large and growing number of published studies, and their
      increasing rate of publication, makes the task of identifying relevant studies in
      an unbiased way for inclusion in systematic reviews both complex and time
      consuming. Text mining has been offered as a potential solution: through
      automating some of the screening process, reviewer time can be saved. The
      evidence base around the use of text mining for screening has not yet been pulled
      together systematically; this systematic review fills that research gap. Focusing
      mainly on non-technical issues, the review aims to increase awareness of the
      potential of these technologies and promote further collaborative research
      between the computer science and systematic review communities. METHODS: Five
      research questions led our review: what is the state of the evidence base; how
      has workload reduction been evaluated; what are the purposes of semi-automation
      and how effective are they; how have key contextual problems of applying text
      mining to the systematic review field been addressed; and what challenges to
      implementation have emerged? We answered these questions using standard
      systematic review methods: systematic and exhaustive searching, quality-assured
      data extraction and a narrative synthesis to synthesise findings. RESULTS: The
      evidence base is active and diverse; there is almost no replication between
      studies or collaboration between research teams and, whilst it is difficult to
      establish any overall conclusions about best approaches, it is clear that
      efficiencies and reductions in workload are potentially achievable. On the whole,
      most suggested that a saving in workload of between 30% and 70% might be
      possible, though sometimes the saving in workload is accompanied by the loss of
      5% of relevant studies (i.e. a 95% recall). CONCLUSIONS: Using text mining to
      prioritise the order in which items are screened should be considered safe and
      ready for use in 'live' reviews. The use of text mining as a 'second screener'
      may also be used cautiously. The use of text mining to eliminate studies
      automatically should be considered promising, but not yet fully proven. In highly
      technical/clinical areas, it may be used with a high degree of confidence; but
      more developmental and evaluative work is needed in other disciplines.

PMID- 25588315
TI  - Estimation of the Binding Free Energy of AC1NX476 to HIV-1 Protease Wild Type and
      Mutations Using Free Energy Perturbation Method.
AB  - The binding mechanism of AC1NX476 to HIV-1 protease wild type and mutations was
      studied by the docking and molecular dynamics simulations. The binding free
      energy was calculated using the double-annihilation binding free energy method.
      It is shown that the binding affinity of AC1NX476 to wild type is higher than not
      only ritonavir but also darunavir, making AC1NX476 become attractive candidate
      for HIV treatment. Our theoretical results are in excellent agreement with the
      experimental data as the correlation coefficient between calculated and
      experimentally measured binding free energies R = 0.993. Residues Asp25-A, Asp29
      A, Asp30-A, Ile47-A, Gly48-A, and Val50-A from chain A, and Asp25-B from chain B
      play a crucial role in the ligand binding. The mutations were found to reduce the
      receptor-ligand interaction by widening the binding cavity, and the binding
      propensity is mainly driven by the van der Waals interaction. Our finding may be
      useful for designing potential drugs to combat with HIV. 

PMID- 25588317
TI  - Comparison of Newcastle disease vaccine administered as powder or liquid in
      relation to the serum antibody response and adverse vaccinal reactions in
      broilers.
AB  - Liquid spray and aerosol mass vaccination of poultry have several drawbacks, such
      as uncontrolled deposition of vaccine particles in the respiratory tract and
      vaccine virus inactivation by formation and evaporation of droplets. These may be
      addressed by using dry powder vaccines with defined particle size distribution
      targeting the upper (primary vaccination) or the entire respiratory tract
      (booster vaccination). Therefore, a coarse Newcastle disease (LZ58 strain) powder
      vaccine was administered to specified pathogen free (SPF) broiler hens to compare
      the antibody response and adverse vaccinal reactions with those induced by a
      coarse liquid spray and a fine liquid aerosol. Groups of 40 broilers each housed
      in isolators were vaccinated at 4 days of age and intratracheally inoculated with
      Escherichia coli (strain 506) at 11 days of age. Adverse vaccinal reactions were
      evaluated by measuring body weight gain and mortality between 4 and 11 days of
      age and between 11 and 18 days of age, and by recording colibacillosis lesions at
      18 days of age. The antibody serum response was measured at 18 days of age by the
      haemagglutination inhibition test. Despite the relative low initial vaccine virus
      loss and narrow particle size distribution of the powder vaccines in comparison
      with their liquid counter parts, no significant differences (P > 0.05) regarding
      adverse vaccinal reactions and antibody response were observed between broilers
      vaccinated with the powder vaccines or with their liquid counterparts. 

PMID- 25588318
TI  - Protective Effects of Glycyrrhizic Acid and 18beta-Glycyrrhetinic Acid against
      Cisplatin-Induced Nephrotoxicity in BALB/c Mice.
AB  - The clinical use of antineoplastic drug cisplatin (CP) is commonly complicated by
      nephrotoxic side effects that limit its application and therapeutic efficiency.
      This study used a model of CP-induced renal injury in male BALB/c mice to
      investigate the protective effects of the active components of licorice,
      glycyrrhizic acid (GA), and 18beta-glycyrrhetinic acid (18betaGA) against CP
      induced nephrotoxicity, and the chemoprotectant, amifostine, was used as a
      control. Oral administration of GA or 18betaGA significantly reduced CP-induced
      increases in the levels of blood urea nitrogen, creatinine, and lactate
      dehydrogenase. Hematoxylin and eosin staining revealed that GA and 18betaGA
      delayed the progression of renal injury, including tubular necrosis, hyaline
      casts, and tubular degeneration in response to CP exposure. Oxidative status and
      inflammatory responses in CP-treated mice were restored to near-normal levels by
      treatment with GA or 18betaGA. These protective effects might be associated with
      upregulation of nuclear factor E2-related protein (Nrf2) and downregulation of
      nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappaB) in the
      kidney. Notably, we demonstrated that GA and 18betaGA rendered renal cells
      resistant to CP-induced HMGB1 cytoplasmic translocation and release. These
      findings suggest that GA and 18betaGA might be act as the chemoprotectants
      against CP-induced nephrotoxicity.

PMID- 25588319
TI  - Delayed tracheobronchial rupture after caustic ingestion.

PMID- 25588320
TI  - Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A
      activity in humans.
AB  - AIM: We aimed to establish a method to assess systemic and pre-systemic
      cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam.
      METHODS: In an open, one sequence, crossover study, 16 healthy participants
      received intravenous and oral midazolam at microgram (0.001 mg intravenous and
      0.003 mg oral) and regular milligram (1 mg intravenous and 3 mg oral) doses to
      assess the linearity of plasma and urine pharmacokinetics. RESULTS: Dose
      normalized AUC and Cmax were 37.1 ng ml(-1 ) h [95% CI 35.5, 40.6] and 39.1 ng
      ml(-1) [95% CI 30.4, 50.2] for the microdose and 39.0 ng ml(-1 ) h [95% CI 36.1,
      42.1] and 37.1 ng ml(-1) [95% CI 26.9, 51.3] for the milligram dose. CLmet was
      253 ml min(-1) [95% CI 201, 318] vs. 278 ml min(-1) [95% CI 248, 311] for
      intravenous doses and 1880 ml min(-1) [95% CI 1590, 2230] vs. 2050 ml min(-1)
      [95% CI 1720, 2450] for oral doses. Oral bioavailability of a midazolam microdose
      was 23.4% [95% CI 20.0, 27.3] vs. 20.9% [95% CI 17.1, 25.5] after the regular
      dose. Hepatic and gut extraction ratios for microgram doses were 0.44 [95% CI
      0.39, 0.49] and 0.53 [95% CI 0.45, 0.63] and compared well with those for
      milligram doses (0.43 [95% CI 0.37, 0.49] and 0.61 [95% CI 0.53, 0.70]).
      CONCLUSION: The pharmacokinetics of an intravenous midazolam microdose is linear
      to the applied regular doses and can be used to assess safely systemic CYP3A
      activity and, in combination with oral microdoses, pre-systemic CYP3A activity.

PMID- 25588321
TI  - Highly precise detection, discrimination, and removal of anionic surfactants over
      the full pH range via cationic conjugated polymer: an efficient strategy to
      facilitate illicit-drug analysis.
AB  - A water-soluble cationic conjugated polyelectrolyte (CPE), poly(1,4-bis(6-(1
      methylimidazolium)-hexyloxy)-benzene bromide) (PMI) displays extraordinary
      stability over the full pH range of 1-14 as well as in seawater, brine, urine,
      and other solutions and carries out efficient detection, discrimination, and
      removal of moderately dissimilar anionic surfactants (viz., sodium dodecyl
      benzenesulfonate (SDBS) and sodium dodecyl sulfate (SDS)) at very low levels
      (31.7 and 17.3 parts per billion (ppb), respectively). PMI formed stable
      hydrogels in the presence of SDS that remained unaffected by strong acids/bases,
      heating, ultrasonication, or exposure to light, whereas SDBS formed precipitate
      with PMI as a result of its different interpolymer cofacial arrangement via
      Columbic attraction. The complex-forming ability of PMI with SDS and SDBS
      facilitated their elimination from water or drug-doped urine samples without the
      use of any organic solvent, chromatographic technique, or solid support. This
      protocol, the first of its kind for the removal of anionic surfactants at very
      low concentrations from any type of solution and competitive environments,
      demonstrates an original application using a CPE. The surfactant-free sample
      solutions could be precisely analyzed for the presence of illicit drugs by any
      standard methods. Using PMI, a newly developed CPE, a rapid and practical method
      for the efficient detection, discrimination, and removal of SDS and SDBS at ppb
      levels from water and urine, under harsh conditions, and in natural chemical
      environments is demonstrated. 

PMID- 25588316
TI  - Metabolic vs. hedonic obesity: a conceptual distinction and its clinical
      implications.
AB  - Body weight is determined via both metabolic and hedonic mechanisms. Metabolic
      regulation of body weight centres around the 'body weight set point', which is
      programmed by energy balance circuitry in the hypothalamus and other specific
      brain regions. The metabolic body weight set point has a genetic basis, but
      exposure to an obesogenic environment may elicit allostatic responses and upward
      drift of the set point, leading to a higher maintained body weight. However, an
      elevated steady-state body weight may also be achieved without an alteration of
      the metabolic set point, via sustained hedonic over-eating, which is governed by
      the reward system of the brain and can override homeostatic metabolic signals.
      While hedonic signals are potent influences in determining food intake, metabolic
      regulation involves the active control of both food intake and energy
      expenditure. When overweight is due to elevation of the metabolic set point
      ('metabolic obesity'), energy expenditure theoretically falls onto the standard
      energy-mass regression line. In contrast, when a steady-state weight is above the
      metabolic set point due to hedonic over-eating ('hedonic obesity'), a persistent
      compensatory increase in energy expenditure per unit metabolic mass may be
      demonstrable. Recognition of the two types of obesity may lead to more effective
      treatment and prevention of obesity. 

PMID- 25588322
TI  - Role of the kidney in the fetal programming of adult cardiovascular disease: an
      update.
AB  - It is well established that an adverse in utero environment can impinge upon
      fetal development and place the offspring on a track leading to future
      cardiovascular disease. Significantly, this may occur in the absence of any
      outward manifestations at birth. In this brief review, we focus on potential
      renal mechanisms that lead to adaptations in glomerular and tubular function that
      initiate hypertension of developmental origin and examine potential therapeutic
      interventions. This report updates recent data in this field. 

PMID- 25588323
TI  - In vitro anti-lithogenic activity of lime powder regimen (LPR) and the effect of
      LPR on urinary risk factors for kidney stone formation in healthy volunteers.
AB  - Hypocitraturia, hypokaliuria, and increased oxidative stress are common
      lithogenic risk factors found in nephrolithiasis patients, especially in
      Thailand. We previously developed lime powder regimen (LPR), and demonstrated
      that LPR delivered citraturic, alkalinizing, and antioxidative effects in kidney
      stone patients. In this study, in vitro anti-lithogenic activity, in vivo acute
      toxicity, and crossover-designed phase 1 trial (in 13 healthy volunteers) of LPR
      were investigated. LPR inhibited the growth of calcium oxalate monohydrate (COM)
      crystals in dose-dependent manner, and inhibited the intracellular production of
      reactive oxygen species (ROS) in COM-treated HK-2 cells. LPR did not
      significantly alter viability of HK-2 cells. No acute toxicity was detected in
      mice orally fed with LPR (10 g/kg). No adverse effect and complaint of LPR
      ingestion (5 g/dose) were observed in the tested volunteers. Plasma citrate was
      elevated at 30 min after LPR load, which was higher than the water load control.
      Plasma potassium was significantly elevated at 30 min after LPR load and remained
      high for 2 h, and at 2 h, it was significantly higher than the water load.
      Urinary citrate was significantly increased at 1 h after LPR load and remained
      high for 2 h, and at 2 h, it was significantly higher than the water load.
      Urinary potassium was significantly increased at 1 h after LPR load and remained
      high for 3 h, and its levels at 1, 2, and 3 h were significantly higher than the
      water load. Urinary total antioxidant status was significantly increased at 2 h
      after LPR load. In conclusion, LPR had an inhibitory effect on COM growth and
      exerted as antioxidant to attenuate ROS production in the COM-treated renal
      tubular cells. LPR provided citraturic, kaliuric, and antioxidative responses in
      healthy individuals without any adverse events. This suggests that LPR is well
      tolerated and safe for daily consumption.

PMID- 25588325
TI  - Primary hepatic myopericytoma with rhabdoid-like cells: Report of the first case
      and review of Literature.

PMID- 25588324
TI  - [Treatment of localized prostate cancer with high-intensity focused ultrasound].
AB  - BACKGROUND: High-intensity focused ultrasound (HIFU) is an alternative technique
      in the treatment of prostate cancer (PC). Despite proven oncologic efficacy, HIFU
      is still not establish as a standard therapy for PC in Germany due to
      insufficient clinical studies. OBJECTIVES: HIFU can be performed as primary whole
      gland treatment, primary focal treatment, or salvage treatment in patients with
      local recurrence after external radiation therapy (RT) or seeds (BT). This paper
      provides an overview of the current significance of HIFU therapy in Germany.
      RESULTS: Primary whole gland HIFU treatment showed approximately similar
      oncologic efficacy and side effects when compared to radical prostatectomy (RP)
      and RT or BT but results were not better than standard therapies. Between the
      priorities of the active standard therapies, on the one hand, and active
      surveillance, on the other, primary focal HIFU treatment may offer a new
      therapeutic approach for patients with low- and early intermediate-risk diseases.
      Diagnostic uncertainties and the lack of validated oncological outcome data are
      currently strong limitations to the results of primary focal treatment. Salvage
      treatment may offer intermediate-term disease-free survival for patients with
      local recurrence after RT or BT, although it may be accompanied by increased side
      effects. CONCLUSION: Currently, there is only little need for an alternative
      whole gland treatment besides RP and RT/BT. The number of patients with low- and
      early intermediate-risk diseases continues to grow. Some of these patients may
      benefit from primary focal HIFU treatment. Prospective multicentric clinical
      trials are needed to validate the oncologic efficacy of primary focal HIFU
      treatment.

PMID- 25588327
TI  - Erratum to: Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A Review of Their
      Basic and Clinical Pharmacology.

PMID- 25588326
TI  - Superior radiation-resistant nanoengineered austenitic 304L stainless steel for
      applications in extreme radiation environments.
AB  - Nuclear energy provides more than 10% of electrical power internationally, and
      the increasing engagement of nuclear energy is essential to meet the rapid
      worldwide increase in energy demand. A paramount challenge in the development of
      advanced nuclear reactors is the discovery of advanced structural materials that
      can endure extreme environments, such as severe neutron irradiation damage at
      high temperatures. It has been known for decades that high dose radiation can
      introduce significant void swelling accompanied by precipitation in austenitic
      stainless steel (SS). Here we report, however, that through nanoengineering,
      ultra-fine grained (UFG) 304 L SS with an average grain size of ~100 nm, can
      withstand Fe ion irradiation at 500  degrees C to 80 displacements-per-atom (dpa)
      with moderate grain coarsening. Compared to coarse grained (CG) counterparts,
      swelling resistance of UFG SS is improved by nearly an order of magnitude and
      swelling rate is reduced by a factor of 5. M(23)C(6) precipitates, abundant in
      irradiated CG SS, are largely absent in UFG SS. This study provides a
      nanoengineering approach to design and discover radiation tolerant metallic
      materials for applications in extreme radiation environments.

PMID- 25588328
TI  - Primary malignant mixed Mullerian tumor of the fallopian tube after subtotal
      hysterectomy: a case report and literature review.

PMID- 25588329
TI  - Distinct demographic factors influence the acceptance of vaccination against HPV.
AB  - PURPOSE: To investigate the possible effect of demographic factors on HPV
      vaccination acceptance in Greece. METHODS: Analysis was performed on data from
      the "LYSISTRATA" project, a prospective, cross-sectional study, focusing on
      questions regarding the acceptance of HPV vaccination among Greek women for
      themselves, and their 13-year-old daughter or son. In total, 5,379 women
      participated in the study, between 2005 and 2011. RESULTS: Women born and raised
      in Greece were more likely to accept HPV vaccination for themselves (aOR = 4.1,
      95 % CI 2.9-5.8), their daughter (aOR = 3.3, 95 % CI 2.3-4.7) and son (aOR = 3.3,
      95 % CI 2.3-4.8), compared with immigrants. Similarly, women who had a
      Papanicolaou's test were more likely to accept vaccination for themselves (aOR =
      1.8, 95 % CI 1.4-2.3), their daughter (aOR = 1.5, 95 % CI 1.2-1.9) and son (aOR =
      1.4, 95 % CI 1.1-1.7) than those never tested. Smokers were less likely to accept
      HPV vaccination for themselves (aOR = 0.8, 95 % CI 0.6-0.9); however, such an
      association was not documented concerning their children. Educational level had a
      rather inconsistent impact on HPV vaccination acceptance. The effect of womens'
      age, monthly income, residence, profession and marital status on HPV vaccination
      acceptance for themselves was different than that for their daughters, and even
      more for their sons. CONCLUSIONS: There are distinct demographic factors that
      influence HPV vaccination acceptance. Women's perception that male vaccination is
      not as necessary may lead to lower acceptance of HPV vaccination for young boys
      and men.

PMID- 25588331
TI  - [Laboratory assessment of deformational features in thermoplastic materials for
      removable dentures].
AB  - The paper presents the results of laboratory tests of base thermoplastic
      materials Acry F711 and Flexi N512 in comparison with the traditional acrylic
      base material Ftoracs to study their deformational properties when loaded by
      repetitive forces close to the functional chewing loads. 

PMID- 25588332
TI  - [Harmonic imaging analysis for assessment of morphological changes in mini-pig
      alveolar bone by normal and increased functional load].
AB  - The aim of the study was to reveal the mastication forces effect on the
      microstructure of mandible bone tissue of mini-pigs by Fouirier harmonic imaging
      analysis of bone sections images of back scattered electrons and assessment of
      calcium and phosphorous distribution maps obtained by roentgenofluorescence
      technique. The results showed that by higher functional loads not only the total
      content of mineral elements in the bone matrix increased but also the of the low
      frequency harmonics in the image spectrum indicating structural heterogeneity
      decrease in bone mineralization. 

PMID- 25588330
TI  - Does metabolic syndrome increase the risk of infective complications after
      prostate biopsy? A critical evaluation.
AB  - PURPOSE: To evaluate the possible association between metabolic syndrome (MetS)
      and infectious complications after prostate biopsy. METHODS: A total of 480 men
      underwent prostatic biopsy due to elevated prostate-specific antigen levels
      and/or abnormal digital rectal examination. Patients were divided into two
      subgroups with respect to the presence or absence of MetS. Patients in both
      groups were closely followed with respect to infectious complications after
      biopsy and the possible effect of MetS as a certain risk factor on these
      complications was evaluated with a multivariate analysis. RESULTS: Infectious
      complications were observed in 33 cases (6.8%), while urinary tract infection
      (UTI) was detected in 30 (6.2%) cases, sepsis occurred in three (0.6%) cases. The
      percentage of the cases with infectious complications was 11.0 and 3.4% in men
      with and without MetS, respectively (p = 0.002). These rates were 3.7 versus
      1.5%, respectively, for UTI (p < 0.003) and 0.9 versus 0.4%, respectively, for
      sepsis in both groups (p = 0.594). Multivariate analysis of the data confirmed
      that MetS was associated with an increased risk of infective complications (odds
      ratio 3.44 and 95% CI 1.56-7.58, p < 0.002) after this procedure. CONCLUSIONS:
      MetS could pose a certain increased risk for infectious complications after
      prostate biopsy. Patients with MetS should be considered as risk cases for this
      procedure, and they should be evaluated and followed in a very close manner with
      respect to these complications.

PMID- 25588334
TI  - [Methods of complex diagnostics of oral leukoplakia].
AB  - The problem of diagnostic of various forms of leukoplakia of the oral mucosa is
      reviewed IT is introduced a set of methods for diagnosis of the disease,
      including a clinical check up, evaluation of the data of optical coherence
      tomography, classical histological and immunohistochemical study to determine the
      neoplastic cell transformation of oral mucosa in the early stages of its
      development. 

PMID- 25588333
TI  - [Antimicrobial efficacy of systemic antibiotics of different groups in the
      complex treatment of patients with chronic periodontal disease].
AB  - Among microorganisms found in the oral cavity there are several kinds of
      periodontopathogenic bacteria having higher adhesive, invasive and toxic
      properties. Eighty patients with moderate and severe chronic generalized
      periodontitis were included in the study. The choice of treatment regimen
      depended on real-time PCR values of pathogenic microorganisms in periodontal
      pockets. Data on composition of periodontal pockets microflora by moderate and
      severe periodontal disease allow prompt target antimicrobial therapy. 

PMID- 25588335
TI  - [Hemodynamic features assessment in submental and facial arteries in patients
      with early atherosclerotic disease of brachycephalic arteries].
AB  - By ultrasonicduplex scanning nature estimated haemodynamics in the
      arteriessubmentalis and facial of patients with early signs of atherosclerotic
      changes in the brakhiotsefalarteries and periodontal pathology of different
      stages - for perfection of prophylaxis of periodontal diseases by the means of
      investigation of prophylaxis vascular diseases. It was established, that
      influence of risk factors is more important than the age of patients. 

PMID- 25588336
TI  - [Comparative study of bacterial flora in patients with chronic periodontal
      disease assessed by various microbiological methods (preliminary study)].
AB  - Periodontal pockets microflora features by aggressive and chronic periodontal
      disease were studied by means of polymerase chain reaction (PCR) and mass
      spectrometry. The study included 14 patients aged 25-70 years without somatic
      pathology. The pilot study has shown the high prevalence rate in obligate
      periodontal pathogens in periodontal pockets revealed by PCR diagnostics, at the
      same time mass spectrometry has revealed the presence of other pathogens which
      had not been primarily included into PRC diagnosis. Periodontal disease,
      periodontal pathogenes, mass spectrometry, PCR diagnostics, periodontal pockets,
      microbiological flora. 

PMID- 25588337
TI  - [Method of root canal retreatment using computer simulation].
AB  - The paper describes a method of root canal retreatment that enables by means of
      CT data, laser surface scanning of teeth and a number of software to create
      plastic templates making possible successful retreatment with minimal risk of
      complications. The effectiveness of the method was evaluated in vitro on 10
      extracted teeth. Application of the method in clinical practice enables the
      highest degree of accuracy and security of the procedure. 

PMID- 25588338
TI  - [Efficiency and safety of local anesthesia in teeth with mild and moderate
      periodontal disease].
AB  - The rationale for the choice of local anesthesia in teeth with mild to moderate
      periodontal disease was formulated based on a comparative analysis of the
      effectiveness and safety of different local anesthesia methods with 4% articaine.
      Effectiveness of anesthesia was assessed using objective values of electric study
      of pulp sensitivity and registration of microcirculation in dental pulp. Safety
      analysis was based on changes in periodontal tissues microcirculation assessed by
      laser Doppler flowmetry, as well as of central hemodynamics rates. 

PMID- 25588339
TI  - [Surgical treatment of patients with drug abuse and mandible necrosis].
AB  - The article describes clinical and radiological classification of osteonecrosis
      of the mandible in patients with drug dependence, surgical options presented on
      the basis of classification proposed. Clinical case of simultaneous application
      of individual plate of nikelid titanium in patient with osteonecrosis of the
      mandible is presented. 

PMID- 25588340
TI  - [PCR rationale for use of oral cephalosporins by oral surgery procedures].
AB  - The article presents the experience of PCR detection of DNA of pathogenic germs
      inducing odontogenic inflammation. Pus samples of 48 patients aged 18 to 68 years
      undergoing oral surgery because of apical periodontal lesions and pericoronitis.
      The results showed microorganisms associations revealed by PCR are sensitive to
      III generation cephalosporins. Effective oral regimen included 400 mg Ceftibuten
      once daily. The PCR results thus served as a rationale for use of oral
      cephalosporins by oral surgery procedures proved by clinical and immunological
      data in postoperative period. 

PMID- 25588342
TI  - [Mandibular condyle fractures fixation via intraoral approach with endoscopic
      assistance].
AB  - The aim of the study was to evaluate the effectiveness of mandibular condyle
      fractures fixation via intraoral approach with endoscopic assistance. Thirty-nine
      patients with low mandibular condyle fractures with lateral (34 patients) or
      medial (5 patients) displacement were included in the study. The paper contains
      detailed description of operation technique considering displacement type. This
      minimally invasive procedure resulted in stable fixation of the fracture so that
      maxillomandibular splinting was limited to 9-14 days after operation. The
      patients were discharged 4 to 7 days postoperatively. The study revealed no cases
      of facial palsies and all patients were highly satisfied with the absence of
      visible scars. 

PMID- 25588341
TI  - [Choice of cystotomy method in patients with cysts of maxillary frontal region
      according to resorption grade of adjacent bony structures].

PMID- 25588343
TI  - [Use of elastopositioner for treatment of masticator muscles discoordination in
      patients with TMJ dysfunction].
AB  - The paper presents the analysis of functional changes in patients with TMJ
      dysfunction before and after the use of elastopositioner. Analysis has shown that
      at the initial stages the device provide relief from pain and masticatory muscles
      hypertension, reduced the bioelectric activity of the muscles. Normalization of
      the lower jaw movements when opening and closing the mouth and reduction of noise
      events in TMJ were also noted. 

PMID- 25588344
TI  - [Stabilometric features of vertical stability in healthy individuals by short
      time bite change].
AB  - The aim of the study was to evaluate vertical stability changes according to
      stabilometric findings under artificial short-time disturbed occlusion. Twelve
      individuals were included in the study and vertical stability was assessed in
      stability platform before and under short-time bite change. The registered
      changes might be connected with an approximate reaction and random reasons. There
      is a possibility of bias by mechanical transfer of the stabilometric study
      results on the diagnosis of dental status. 

PMID- 25588345
TI  - [The experience of complex treatment of children with bilateral cleft lip and
      palate].
AB  - Three grades of premaxilla deformation were revealed in children with bilateral
      cleft lip and palate. All patients with grade I and some children with grade II
      deformation received early orthopedic treatment by Sharova appliance while in
      patients with grade III deformation orthodontic devices with bone fixation with
      microimplants were used or microimplants alone for orthodontic anchorage. This
      approach allowed achieving full side contact of premaxilla and maxillary
      fragments in 1-2 months thus creating favorable conditions for surgical
      procedure. 

PMID- 25588347
TI  - Retraction. Breast cancer surgery in elderly patients: postoperative
      complications and survival.

PMID- 25588346
TI  - Investigation of mosquito oviposition pheromone as lethal lure for the control of
      Aedes aegypti (L.) (Diptera: Culicidae).
AB  - BACKGROUND: The trend in chemical insecticide development has focused on
      improving the efficacy against mosquitoes while reducing the environmental
      impact. Lethal lures apply an "attract-and-kill" strategy that draws the insect
      to the killing agent rather than bringing the killing agent to the insect.
      METHODS: In this study, the mosquito oviposition pheromone was extracted from the
      eggs of Aedes aegypti (L.) and further investigated with a combination of
      pheromone and granular temephos as a lethal lure. RESULTS: The compound caproic
      acid attracted significantly more egg-laying mosquitos at 1 ppm (660.83 +/-
      91.61) than the control (343.83 +/- 56.24), which consisted of solvent only
      (Oviposition Activity Index: 0.316). Further investigation of the combination of
      caproic acid with granular temephos as a lethal lure attracted significantly more
      gravid female Ae. aegypti to oviposit their eggs than the temephos treated water
      and control. CONCLUSIONS: This indicated the ability of caproic acid in acting as
      an attractant and counters the repellency effect of temephos. Additionally, the
      presence of temephos in the lethal lure also restricted the hatching of the eggs
      and killed any larvae that hatched.

PMID- 25588348
TI  - An optopneumatic piston for microfluidics.
AB  - We demonstrate an optopneumatic piston based on glass capillaries, a mixture of
      PDMS-carbon nanopowder, silicone and mineral oil. The fabrication method is based
      on wire coating techniques and surface tension-driven instabilities, and allows
      for the assembly of several pistons from a single batch production. By coupling
      the photothermal response of the PDMS-carbon mixture with optical excitation via
      an optical fiber, we demonstrate that the piston can work either as a valve or as
      a reciprocal actuator. The death volume of the pistons was between 0.02 and 1.56
      MUL and the maximum working frequency was around 1 Hz. Analysis of the motion
      during the expansion/contraction of the piston shows that this machine can be
      described by a phenomenological equation analogous to the Kelvin-Voight model
      used in viscoelasticity, having elastic and viscous components. 

PMID- 25588349
TI  - Aggregation behavior of a gemini surfactant with a tripeptide spacer.
AB  - A peptide gemini surfactant, 12-G(NH2)LG(NH2)-12, has been constructed with two
      dodecyl chains separately attached to the two terminals of a glutamic acid-lysine
      glutamic acid peptide and the aggregation behavior of the surfactant was studied
      in aqueous solution. The 12-G(NH2)LG(NH2)-12 molecules form fiber-like
      precipitates around pH 7.0, and the precipitation range is widened on increasing
      the concentration. At pHs 3.0 and 11.0, 12-G(NH2)LG(NH2)-12 forms soluble
      aggregates because each molecule carries two positively charged amino groups at
      the two ends of the peptide spacer at pH 3.0, while each molecule carries one
      negatively charged carboxyl group in the middle of the peptide spacer at pH 11.0.
      12-G(NH2)LG(NH2)-12 displays a similar concentration-dependent process at these
      two pHs: forming small micelles above the critical micelle concentration and
      transferring to fibers at pH 3.0 or twisted ribbons at pH 11.0 above the second
      critical concentration. The fibers formed at pH 3.0 tend to aggregate into
      bundles with twisted structure. Both the twisted fibers at pH 3.0 and the twisted
      ribbons at pH 11.0 contain beta-sheet structure formed by the peptide spacer. 

PMID- 25588350
TI  - Novel FGG variant (gamma339C->S) confirms importance of the gamma326-339
      disulphide bond for plasma expression of newly synthesised fibrinogen.

PMID- 25588352
TI  - The strain rate effect on the buckling of single-layer MoS2.
AB  - The Euler buckling theory states that the buckling critical strain is an inverse
      quadratic function of the length for a thin plate in the static compression
      process. However, the suitability of this theory in the dynamical process is
      unclear, so we perform molecular dynamics simulations to examine the
      applicability of the Euler buckling theory for the fast compression of the single
      layer MoS2. We find that the Euler buckling theory is not applicable in such
      dynamical process, as the buckling critical strain becomes a length-independent
      constant in the buckled system with many ripples. However, the Euler buckling
      theory can be resumed in the dynamical process after restricting the theory to an
      individual ripple in the buckled structure. 

PMID- 25588353
TI  - Long-term safety and maintenance of efficacy of levodopa-carbidopa intestinal
      gel: an open-label extension of the double-blind pivotal study in advanced
      Parkinson's disease patients.
AB  - BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is delivered continuously
      via intrajejunal percutaneous gastrostomy tube. OBJECTIVE: To examine long-term
      safety, efficacy and quality of life of LCIG in an open-label extension study.
      METHODS: Patients received 52 weeks of open-label LCIG treatment following a 12
      week double-blind, double-dummy trial in which they were randomized to either
      LCIG or immediate-release oral levodopa-carbidopa. Patient cohort designation was
      by receipt of LCIG in the preceding trial randomization (continuing-LCIG vs. LCIG
      naive patients). RESULTS: Sixty-two of 66 subjects in the double-blind proceeded
      to the open-label extension. Most subjects (95%) reported >=1 adverse event (AE);
      only 3 subjects (4.8%) discontinued due to AEs. AE incidence declined gradually
      over 52 weeks. Serious AEs were reported by 23%. LCIG-naive patients (N = 29)
      showed a decrease in "Off" time and an increase in "On" time without troublesome
      dyskinesia (change from baseline to final visit in mean [SD] hours = -2.34 [2.78]
      P < 0.001 and 2.19 [3.70] P = 0.005, respectively), while continuing-LCIG
      patients (N = 33) showed sustained "Off" time duration and further improvement in
      "On" time without troublesome dyskinesia (-0.42 [2.67] P = 0.377 and 1.00 [2.58]
      P = 0.036, respectively). The majority of patients in both groups (LCIG-naive,
      continuing-LCIG, respectively) were rated 'Much Improved' or 'Very Much Improved'
      at final visit on the Clinical Global Impression-Improvement scale (69.0%,
      69.7%). CONCLUSIONS: Continuing-LCIG patients continued to derive benefit from
      LCIG while the magnitude of improvement among LCIG-naive patients was similar to
      that observed for patients on LCIG in the preceding double-blind study. The
      overall AE profile was consistent with previous phase 3 clinical trials involving
      the LCIG system.

PMID- 25588355
TI  - Sleep correlates of trait executive function and memory in Parkinson's disease.
AB  - BACKGROUND: Sleep disturbance and cognitive impairment are correlated in non
      diseased populations, but their association in Parkinson's disease (PD) is
      uncertain. Prior studies examining measures of cognition in relation to sleep
      have used either self-report or actigraphically measured sleep and have produced
      conflicting findings. OBJECTIVE: In this descriptive study, we correlated
      measurements of sleep in PD patients derived from the gold-standard measurement,
      in-lab polysomnography, with an extensive battery of cognitive measures. We
      hypothesized that poorer sleep would be related to relatively more impaired
      cognition. METHODS: Idiopathic PD patients (n = 34) completed a cognitive battery
      encompassing three broad domains (executive function, immediate memory and
      delayed memory), and underwent PSG for two nights. Scores for each domain from
      individual cognitive measures were converted to z-scores and then averaged to
      produce a composite score. We used second night PSG data and quantified measures
      of sleep architecture, sleep continuity, sleep apnea and nocturnal movement
      (periodic leg movements, PLMS). RESULTS: Lower executive function was associated
      with higher PLMS after controlling for chronological age, mini-mental state
      examination scores, and UPDRS motor subscale scores. These results were
      independent from psychomotor speed. There was a marginally significant positive
      correlation between the proportion of time spent in REM and immediate recall
      ability. Measures of sleep continuity and sleep apnea were unrelated to cognition
      in these patients. CONCLUSIONS: PLMS, known to be a frequent feature of PSG
      measured sleep in PD, may be an important correlate of impaired executive
      function in PD. Whether treating this disorder of sleep results in improvement in
      cognition remains to be determined.

PMID- 25588356
TI  - Social Cognition Impairments in Mice Overexpressing Alpha-Synuclein Under the
      Thy1 Promoter, a Model of Pre-manifest Parkinson's Disease.
AB  - BACKGROUND: Patients with Parkinson's disease (PD) may exhibit deficits in
      "Theory of Mind", the ability to read others' mental states and react
      appropriately, a prerequisite for successful social interaction. Alpha-synuclein
      overexpression is widely distributed in the brain of patients with sporadic PD,
      suggesting that it may contribute to the non-motor deficits observed in PD
      patients. Mice over-expressing human wild-type alpha-synuclein under the Thy1
      promoter (Thy1-aSyn mice) have synaptic deficits in the frontostriatal pathway,
      low cortical acetylcholine, and high level of expression of mGluR5 receptors,
      which have all been implicated in social recognition deficits. OBJECTIVE: To
      determine whether Thy1-aSyn mice present alterations in their response to social
      stimuli. METHODS: We have submitted Thy1-aSyn mice to tests adapted from autism
      models. RESULTS: At 7-8 month of age Thy1-aSyn mice explored their conspecifics
      significantly less than did wild-type littermates, without differences in
      exploration of inanimate objects, and pairs of Thy1-aSyn mice were involved in
      reciprocal interactions for a shorter duration than wild-type mice at this age.
      These deficits persisted when the test animal was enclosed in a beaker and were
      not present at 3-4 months of age despite the presence of olfactory deficits at
      that age, indicating that they were not solely caused by impairment in olfaction.
      CONCLUSION: Thy1-aSyn mice present progressive deficits in social recognition,
      supporting an association between alpha-synuclein overexpression and Theory of
      Mind deficits in PD and providing a useful model for identifying mechanisms and
      testing novel treatments for these deficits which impact patients and caretakers
      quality of life.

PMID- 25588357
TI  - Participatory design in Parkinson's research with focus on the symptomatic
      domains to be measured.
AB  - BACKGROUND: There is a growing interest in the objective assessment of health
      related outcomes using technology providing quality measurements to be applied
      not only in daily clinical practice, but also in scientific research. Differences
      in the understandings of the condition and the terminology used between people
      with Parkinson's (PwPs), clinicians and technical developers may influence the
      progress of a participatory design process. OBJECTIVE: This paper reports on a
      participatory design process to achieve a consensus among PwPs, clinicians and
      technologists over the selection of a set of symptomatic domains to be
      continuously assessed, in order to provide results relevant to both PwPs and
      clinicians. METHODS: The methods used were a Web based user survey, end-user
      focus groups, ranking by combined methods, a Delphi process performed among
      clinicians and scientists, and prioritization of the results in a concertation
      workshop for PwPs, clinicians and technologists. RESULTS: The following
      symptomatic domains were commonly agreed by PwPs and clinicians to be of central
      importance in a system of continuous assessment: hypokinesia/bradykinesia,
      tremor, sway, gait, sleep and cognition. This list satisfied both the needs of
      the PwPs and the concerns of the clinicians regarding the means of advancing new
      strategies in assessment and interventions in PD. CONCLUSIONS: A participatory
      design strategy allowed the definition of a consensual list of symptomatic
      domains. Both the strategy and the achieved results may be of relevance for
      similar interdisciplinary approaches in the field of PD using a participatory
      design involving patients, clinicians and technologists.

PMID- 25588358
TI  - Using lanthanide ions in molecular bioimaging.
AB  - Trivalent lanthanide ions offer remarkable opportunities in the design of
      bioimaging agents: this review presents an accessible discussion of their
      application in both optical and magnetic resonance imaging. Aspects of molecular
      design, control over key physical properties and biological compatibility are
      discussed in this context, together with developments and opportunities as
      responsive probes and in multimodal imaging. 

PMID- 25588359
TI  - Response to: A rapid skeletal turnover in radiographic mimic of osteopetrosis
      might be secondary to systemic mastocytosis.

PMID- 25588354
TI  - Role of alpha-synuclein in inducing innate and adaptive immunity in Parkinson
      disease.
AB  - Alpha-synuclein (alpha-syn) is central to the pathogenesis of Parkinson disease
      (PD). Gene duplications, triplications and point mutations in SNCA1, the gene
      encoding alpha-syn, cause autosomal dominant forms of PD. Aggregated and post
      translationally modified forms of alpha-syn are present in Lewy bodies and Lewy
      neurites in both sporadic and familial PD, and recent work has emphasized the
      prion-like ability of aggregated alpha-syn to produce spreading pathology.
      Accumulation of abnormal forms of alpha-syn is a trigger for PD, but recent
      evidence suggests that much of the downstream neurodegeneration may result from
      inflammatory responses. Components of both the innate and adaptive immune systems
      are activated in PD, and influencing interactions between innate and adaptive
      immune components has been shown to modify the pathological process in animal
      models of PD. Understanding the relationship between alpha-syn and subsequent
      inflammation may reveal novel targets for neuroprotective interventions. In this
      review, we examine the role of alpha-syn and modified forms of this protein in
      the initiation of innate and adaptive immune responses. 

PMID- 25588361
TI  - Experimental and theoretical charge density distribution in Pigment Yellow 101.
AB  - The charge density distribution in 2,2'-dihydroxy-1,1'-naphthalazine (Pigment
      Yellow 101; P.Y.101) has been determined using high-resolution X-ray diffraction
      and multipole refinement, along with density functional theory calculations.
      Topological analysis of the resulting densities highlights the localisation of
      single/double bonds in the central C=N-N=C moiety of the molecule in its ground
      state. The density in the N-N is examined in detail, where we show that very
      small differences between experiment and theory are amplified by use of the
      Laplacian of the density. Quantification of hydrogen bonds highlights the
      importance of the intramolecular N-H...O interaction, known to be vital for
      retention of fluorescence in the solid state, relative to the many but weak
      intermolecular contacts located. However, a popular method for deriving H-bond
      strengths from density data appears to struggle with the intramolecular N-H...O
      interaction. We also show that theoretical estimation of anisotropic
      displacements for hydrogen atoms brings little benefit overall, and degrades
      agreement with experiment for one intra-molecular contact.

PMID- 25588360
TI  - The role of postoperative chemoradiation for oropharynx carcinoma: a critical
      appraisal of the published literature and National Comprehensive Cancer Network
      guidelines.
AB  - The National Comprehensive Cancer Network (NCCN) describes the presence of
      extracapsular spread and/or positive margins in oropharynx cancer (OPC) as an
      indication for the addition of chemotherapy to postoperative radiation. The
      guideline's category 1 consensus is based on what they term high-level evidence.
      For this study, the authors performed a critical appraisal of the research upon
      which the NCCN guideline is based and assessed its relevance in the era of human
      papillomavirus (HPV)/p16-positive OPC. Multiple shortcomings were identified,
      including patient exclusion after randomization and the use of unplanned subgroup
      analyses without multivariate adjustment, which undermined internal validity.
      Indeterminate HPV/p16 status limited external validity. Given the unique biology
      of HPV/p16-positive tumors and the problems of internal and external validity,
      the authors concluded that the literature upon which the recommendation for the
      addition of chemotherapy to adjuvant radiation was based does not generate high
      level evidence, and its relevance for the postoperative management of patients
      with HPV/p16-positive OPC remains unknown.

PMID- 25588363
TI  - Erratum to: Comparative assessment of surgeons' task performance and surgical
      ergonomics associated with conventional and modified flank positions: a
      simulation study.

PMID- 25588362
TI  - National outcomes of laparoscopic Heller myotomy: operative complications and
      risk factors for adverse events.
AB  - INTRODUCTION: Laparoscopic Heller myotomy (LHM) has supplanted an open approach
      due to decreased operative morbidity. Our goal was to quantify the incidence of
      peri-operative complications and identify risk factors for adverse outcomes in
      LHM. METHODS: All LHM were queried from 2005 to 2011 from the National Surgical
      Quality Improvement Program database. Adverse outcomes were identified, and
      univariate and stepwise logistic regression (MVR) was then performed to quantify
      association. RESULTS: There were 1,237 LHM in the study period. Patient averages
      were: age 51.9 +/- 16.8 years, BMI 27.3 +/- 6.6 kg/m(2), Charlson comorbidity
      index (CCI) 0.2 +/- 0.6. 15.3 % had >10 % body mass loss in the preoperative 6
      months. During surgery, 10.2 % underwent concomitant EGD, and mean operative time
      was 141.6 +/- 63.4 min. There were 7(0.06 %) wound complications, 22(1.8 %)
      general complications, and 30(2.4 %) major complications. Average length of stay
      (LOS) was 2.8 +/- 5.5 days. The rate of readmission and reoperation were 3.1 and
      2.3 %, respectively, and there were 4(0.03 %) deaths. General and major
      complications were associated with alcohol use, pack-years of smoking, weight
      loss, history of stroke, radiation therapy, and longer operative times (p <
      0.05); however, these factors did not remain significant on MVR (p > 0.05).
      Operative time was found to be significantly longer by 35.3 min for inpatients,
      43.1 min in functionally dependent patients, 50.0 min in preoperative septic
      patients, and 17.2 min with concomitant EGD (p < 0.01 for all). LOS was found to
      be longer by 1.9 days for inpatients, 1.8 days in ASA category >=3, and 1.2 days
      per one point increase in CCI (p < 0.001 for all). CONCLUSION: LHM is being
      performed nationally with a low incidence of operative complications and
      mortality. General and major complications following LHM are associated with
      patient alcohol use, pack-years of smoking, weight loss, history of stroke,
      radiation therapy, and longer operative times. Additionally, independent
      predictors of longer operative time and LOS were identified.

PMID- 25588364
TI  - Biliary metal stents for proximal esophageal or hypopharyngeal strictures.
AB  - INTRODUCTION: Endoscopic dilation is the standard of care for stenoses of the
      cervical esophagus, but refractory strictures require some form of stenting. Most
      endoscopists avoid the placement of metal stents near the upper esophageal
      sphincter as they can cause major problems like severe cervical pain and globus
      sensation. We report our results with the use of biliary SEMS in the upper
      esophagus, which have a smaller diameter than regular esophageal stents and
      therefore exert less expansive force. MATERIAL AND METHODS: We retrospectively
      reviewed all patients in our center between July 2011 and June 2014 who received
      a biliary metal stent because of a refractory stricture in the cervical
      esophagus. We implanted biliary SEMS (Wallflex, Boston Scientific) with a
      diameter of 1 cm and length of 6-8 cm. Technical and clinical success, adverse
      events and duration of stenting were evaluated. RESULTS: Ten patients were
      treated with biliary SEMS in the upper esophagus. Strictures were located between
      10 and 19 cm from incisor teeth. Stent placement was successful in all (10/10)
      patients. One stent had to be extracted because of pain and globus sensation.
      Apart from that stent tolerability was good. All remaining patients (9/9)
      reported improvement of dysphagia with a decrease in mean dysphagia score from
      3.2 to 1.78. Mean duration of stenting was 68 days. DISCUSSION: Because of a high
      clinical success rate and good tolerability, biliary metal stents are a
      reasonable alternative for difficult strictures in the cervical esophagus,
      especially in the palliative setting.

PMID- 25588366
TI  - The improvement of the dissolution rate of ziprasidone free base from solid oral
      formulations.
AB  - This work aims at increasing solubility and dissolution rate of ziprasidone free
      base-Biopharmaceutics Classifaction System (BCS) class II compound. The authors
      describe a practical approach to amorphization and highlight problems that may
      occur during the development of formulations containing amorphous ziprasidone,
      which was obtained by grinding in high-energy planetary ball mills or cryogenic
      mills. The release of ziprasidone free base from the developed formulations was
      compared to the reference drug product containing crystalline ziprasidone
      hydrochloride-Zeldox(r) hard gelatin capsules. All preparations were investigated
      using compendial tests (USP apparatuses II and IV) as well as novel, biorelevant
      dissolution tests. The novel test methods simulate additional elements of
      mechanical and hydrodynamic stresses, which have an impact on solid oral dosage
      forms, especially during gastric emptying. This step may prove to be particularly
      important for many formulations of BCS class II drugs that are often
      characterized by narrow absorption window, such as ziprasidone. The dissolution
      rate of the developed ziprasidone free base preparations was found to be
      comparable or even higher than in the case of the reference formulation
      containing ziprasidone hydrochloride, whose water solubility is about 400 times
      higher than its free base. 

PMID- 25588365
TI  - A gastrointestinal transit study on amphotericin B-loaded solid lipid
      nanoparticles in rats.
AB  - The gastrointestinal (GI) transit behavior of and absorption from an amphotericin
      B (AmB) solid lipid nanoformulation (SLN) in rats was investigated. We aimed to
      estimate the gastric emptying time (GET) and cecal arrival time (CAT) of AmB SLN
      in rats as animal models. From these two parameters, an insight on the absorption
      window of AmB was ascertained. Three types of SLNs, AmB, paracetamol (PAR), and
      sulfasalazine (SSZ), were similarly formulated using beeswax/theobroma oil
      composite as the lipid matrix and characterized with regard to size, viscosity,
      density, migration propensity within agarose gel, in vitro drug release,
      morphology, gastrointestinal transit, and in vivo absorption. The GET and CAT
      were estimated indirectly using marker drugs: PAR and sulfapyridine (SP). All
      three types of SLNs exhibited identical properties with regard to z-average,
      viscosity, relative density, and propensity to migrate. PAR was absorbed rapidly
      from the small intestine following emptying of the SLNs giving the T50E (time for
      50% absorption of PAR) to be 1.6 h. SP was absorbed after release and microbial
      degradation of SSZ from SLN in the colon with a lag time of 2 h post
      administration, serving as the estimated cecal arrival time of the SLNs. AmB
      within SLN was favorably absorbed from the small intestine, albeit slowly. 

PMID- 25588367
TI  - A non-invasive method for the determination of liquid injectables by Raman
      spectroscopy.
AB  - Drug safety has become a very important subject, and more countries have joined
      in the fight against counterfeit drugs. This study demonstrated a non-invasive
      Raman spectroscopy method that could be utilized for screening liquid injectable
      drugs for spurious/falsely-labeled/falsified/counterfeit medical products
      (SFFCs). Two problems were solved to remove the blocks in identification and
      quantitation: one problem was the weak API signal extraction from the non
      invasive Raman spectra and the other was the problem of Raman absolute
      measurement. Principal component analysis (PCA) and classical least square (CLS)
      algorithms were performed to establish the models. Water was chosen as the
      "internal standard" to normalize the spectra to solve the problem of Raman
      absolute measurement. The results showed that the 11 positive samples and 66
      negative samples were all well identified with a threshold of 0.95. One of the
      positive samples contained the excipient propylene glycol, which was identified
      successfully at the same time. The accuracy of quantitative results was
      approximately 5% for doxofylline liquid injectables and about 10% for the low
      concentration and big glass bottle-containers of Levofloxacin Lactate and Sodium
      Chloride Injections as compared to the results using an HPLC method, this is
      satisfactory for fast screening of SFFCs. In conclusion, with the development of
      a database of identification and quantitation models, this method may determine
      liquid injectable drugs in a fast and non-invasive way and become one of the most
      powerful weapons against SFFCs. Graphical Abstract ?. 

PMID- 25588368
TI  - The fate of NHC-stabilized dicarbon.
AB  - The attempted synthesis of NHC-stabilized dicarbon (NHC=C=C=NHC) through
      deprotonation of a doubly protonated precursor ([NHC-CH=CH-NHC](2+) ) is
      reported. Rather than deprotonation, a clean reduction to NHC=CH-CH=NHC is
      observed with a variety of bases. The apparent resistance towards deprotonation
      to the target compound led to a reinvestigation of the electronic structure of
      NHC->C?C<-NHC, which showed that the highest occupied molecular orbital/lowest
      unoccupied molecular orbital (HOMO/LUMO) gap is likely too small to allow for
      isolation of this species. This is in contrast to the recent isolation of the
      cyclic alkylaminocarbene analogue (cAAC=C=C=cAAC), which has a large HOMO-LUMO
      gap. A detailed theoretical study illuminates the differences in electronic
      structures between these molecules, highlighting another case of the potential
      advantages of using cAAC rather than NHC as a ligand. The bonding analysis
      suggests that the dicarbon compounds are well represented in terms of donor
      acceptor interactions L->C2 <-L (L=NHC, cAAC).

PMID- 25588369
TI  - Clinical evaluation of Moro (Citrus sinensis (L.) Osbeck) orange juice
      supplementation for the weight management.
AB  - In the last years, several studies have recently evaluated the beneficial effects
      of red orange juice (Citrus sinensis (L.) Osbeck) and its active components in
      weight management and obesity. Moro orange is a cultivar of red orange,
      particularly rich in active compounds such as anthocyanins, hydroxycinnamic
      acids, flavone glycosides and ascorbic acid, which displays anti-obesity effects
      in in vitro and in vivo studies. In this clinical study, the effect of a Moro
      juice extract (Morosil((r)), 400 mg/die) supplementation was evaluated in
      overweight healthy human volunteers for 12 weeks. Results showed that Moro juice
      extract intake was able to induce a significant reduction in body mass index
      (BMI) after 4 weeks of treatment (p < 0.05). Moreover, in subjects treated with
      Moro extract, body weight, BMI, waist and hip circumference were significantly
      different from the placebo group (p < 0.05). In conclusion, it could be suggested
      that the active compounds contained in Moro juice have a synergistic effect on
      fat accumulation in humans and Moro juice extract can be used in weight
      management and in the prevention of human obesity.

PMID- 25588370
TI  - The lack of efficacy of oxytocin and NSAIDs.

PMID- 25588371
TI  - Relationship between cigarette smoking and radiographic knee osteoarthritis in
      Chinese population: a cross-sectional study.
AB  - The purpose of this paper was to estimate the cross-sectional association between
      cigarette smoking and radiographic knee Osteoarthritis (OA) in Chinese
      population. A total of 3,789 subjects (1,796 females and 1,993 males)
      participated in this study. A subject was diagnosed with radiographic knee OA if
      Kellgren-Lawrence (K-L) grade >=2 in at least one leg. The smoking status was
      classified into four levels based on the daily smoking habit: (1) 0/day; (2) 1
      10/day; (3) 11-20/day; and (4) >20/day. Linear trend and multivariable logistic
      regression were conducted for statistical analysis. The prevalence of
      radiographic knee OA was 28.4 % among the subjects of this study. An inverse
      association was observed between cigarette smoking and radiographic knee OA in
      the linear trend test. Such association remained valid after adjusting the
      factors of age, gender, body mass index, betel quilt chewing status, physical
      activity, alcohol drinking status, mean total energy intake and educational level
      in the multivariable logistic regression. This study suggested a negative
      association between cigarette smoking and radiographic knee OA in the Chinese
      population. The findings of this study need to be confirmed by further
      prospective research. 

PMID- 25588372
TI  - Current cigarette use in rheumatoid arthritis patients: associated factors and a
      limited mediating role of depression.
AB  - Some newly published studies revealed that current smoking was associated with
      accelerated disease progression in diagnosed rheumatoid arthritis (RA) patients.
      The major aims of this study were to analyze the associated factors of current
      smoking in RA patients and explore the mediating role of depression in the
      associations between identified factors and smoking. RA patients were selected
      from NHANES databases 2005-2012. Current smoking was determined by race-specific
      serum cotinine levels. Depression was measured by the Depression Screener
      questionnaire. Totally, 848 RA patients were identified and included into final
      analysis. Logistic regression model founds that age, race, and socioeconomic
      status (SES) were associated with current smoking in RA patients: the odds ratios
      (ORs) of smoking were 0.29 (95 % CI 0.17, 0.49) and 0.39 (95 % CI 0.24, 0.62) in
      patients over 60 years old and of higher SES, respectively; non-Hispanic white
      patients with a pre-RA smoking history had an OR of 3.48 (95 % CI 1.35, 5.18)
      when compared with patients of other race with no pre-RA smoking history.
      Structural equation model identified a weak mediating role of depression, only
      accounted for 5 % of the total SES-smoking association. In this sample of
      diagnosed RA patients, age, SES, ethnicity, but not depression, were
      significantly associated with current smoking. 

PMID- 25588373
TI  - Opioid and chemokine receptor crosstalk: a promising target for pain therapy?
AB  - Chemokines and opioids are important regulators of immune, inflammatory and
      neuronal responses in peripheral and central pain pathways. Recent studies have
      provided insights into the functional interactions between chemokine receptors
      and opioid receptors, and their role in pain modulation. In this Progress
      article, we discuss how crosstalk between these two systems might provide a
      molecular and cellular framework for the development of novel analgesic therapies
      for the management of acute and/or chronic pain. 

PMID- 25588381
TI  - Scotland's evidence based outcomes framework for problem drug use.

PMID- 25588380
TI  - Psychological treatments are effective for depression in primary care, study
      shows.

PMID- 25588382
TI  - "Frustrated," "depressed," and "devastated" pediatric trainees: US academic
      medical centers fail to provide adequate workplace breastfeeding support.
AB  - BACKGROUND: Exclusive breastfeeding (EBF) is recommended until about 6 months of
      age. Pediatricians are at the forefront of encouraging mothers to achieve this
      goal, yet pediatricians who parent during their training may face substantial
      barriers in achieving their own breastfeeding goals. OBJECTIVES: This study aimed
      to assess breastfeeding support available to US pediatricians in training and the
      effect of trainees' personal experiences on their attitude toward breastfeeding.
      METHODS: An online survey was emailed to American Academy of Pediatrics Section
      on Medical Students, Residents, and Fellowship Trainees members. RESULTS: There
      were 927 respondents, of which 421 had children and 346 breastfed their children.
      Almost 80% agreed that 6 months is the ideal duration for EBF. One in 4 did not
      have access to or were not aware of a private room to express milk or breastfeed.
      Forty percent needed to extend the duration of their training for a longer
      maternity leave, with breastfeeding a factor for longer leave among 44%. One in 4
      did not meet their breastfeeding duration goal, and 1 in 3 did not meet their
      goal for EBF. Negative emotions were common among those not meeting goals. Ninety
      two percent felt that their or their partner's experience with breastfeeding
      affected their clinical interaction with patients' mothers. CONCLUSION: A
      majority of respondents cited problems with breastfeeding support during
      training, and many failed to meet their intended goals. Not meeting personal
      breastfeeding goals was associated with negative emotions and influenced how they
      counsel about breastfeeding as a result of personal and often negative attitudes.

PMID- 25588383
TI  - The relationship between deprivation and alcohol-related presentation at Accident
      and Emergency (A&E) over a three-month period.
AB  - OBJECTIVES: To identify any relationship between deprivation and the level of
      presentation to Accident and Emergency with alcohol-related conditions in a busy
      East Coast teaching hospital in Scotland. METHODS: Over an 87-day-period initial
      screening to determine whether alcohol played a part in each presentation was
      conducted at triage. These patients were then streamed according to their
      Paddington Alcohol Test (Pat) score into Pat +ve and Pat -ve groups. The postcode
      of each patient was recorded before they were assigned deprivation levels using
      the DepCat scoring system. This information was then compiled in Microsoft Excel
      2003 and a graph showing the differences in the number of presentations across
      the social spectrum was constructed. RESULTS: Nine hundred and forty four
      patients were screened as attending due to alcohol with 43.86% being Pat +ve and
      56.14% being Pat -ve. Overall 66.42% of the Pat +ve group and 54.42% of Pat -ve
      were from deprived or very deprived areas. CONCLUSIONS: The use of electronic
      based screening was effective at highlighting patients presenting to Accident and
      Emergency with alcohol-related problems, and these presentations highlighted a
      direct link between the level of deprivation and attendances.

PMID- 25588379
TI  - Integrated PK-PD and agent-based modeling in oncology.
AB  - Mathematical modeling has become a valuable tool that strives to complement
      conventional biomedical research modalities in order to predict experimental
      outcome, generate new medical hypotheses, and optimize clinical therapies. Two
      specific approaches, pharmacokinetic-pharmacodynamic (PK-PD) modeling, and agent
      based modeling (ABM), have been widely applied in cancer research. While they
      have made important contributions on their own (e.g., PK-PD in examining
      chemotherapy drug efficacy and resistance, and ABM in describing and predicting
      tumor growth and metastasis), only a few groups have started to combine both
      approaches together in an effort to gain more insights into the details of drug
      dynamics and the resulting impact on tumor growth. In this review, we focus our
      discussion on some of the most recent modeling studies building on a combined PK
      PD and ABM approach that have generated experimentally testable hypotheses. Some
      future directions are also discussed. 

PMID- 25588384
TI  - Impact of nutrition on ageing the process. Bridging the gap: the animal
      perspective.
AB  - In pets, as in humans, there is increasing interest in interventions that promote
      'health and well-being' into later life and extend these beyond their current
      limits. The purpose of this review was to assess the relevance of current
      knowledge of ageing in humans, described in a companion paper, as well as
      reviewing recent research on ageing in pet populations. The role of diet and
      other factors that influence the ageing process and ultimately lifespan in pets
      are highlighted in this review; in addition, future opportunities and challenges
      to further our understanding of the ageing process in pets are identified.
      Advancing knowledge of the fundamental biology of ageing will be key for the
      development and evaluation of strategies that extend both the quality and the
      quantity of lifespan in human and pet populations. 

PMID- 25588378
TI  - Spreading of pathology in neurodegenerative diseases: a focus on human studies.
AB  - The progression of many neurodegenerative diseases is thought to be driven by the
      template-directed misfolding, seeded aggregation and cell-cell transmission of
      characteristic disease-related proteins, leading to the sequential dissemination
      of pathological protein aggregates. Recent evidence strongly suggests that the
      anatomical connections made by neurons - in addition to the intrinsic
      characteristics of neurons, such as morphology and gene expression profile -
      determine whether they are vulnerable to degeneration in these disorders.
      Notably, this common pathogenic principle opens up opportunities for pursuing
      novel targets for therapeutic interventions for these neurodegenerative
      disorders. We review recent evidence that supports the notion of neuron-neuron
      protein propagation, with a focus on neuropathological and positron emission
      tomography imaging studies in humans. 

PMID- 25588385
TI  - Maternal depression, stress and feeding styles: towards a framework for theory
      and research in child obesity.
AB  - Against the background of rising rates of obesity in children and adults in the
      USA, and modest effect sizes for obesity interventions, the aim of the present
      narrative review paper is to extend the UNICEF care model to focus on childhood
      obesity and its associated risks with an emphasis on the emotional climate of the
      parent-child relationship within the family. Specifically, we extended the UNICEF
      model by applying the systems approach to childhood obesity and by combining
      previously unintegrated sets of literature across multiple disciplines including
      developmental psychology, clinical psychology and nutrition. Specifically, we
      modified the extended care model by explicitly integrating new linkages (i.e.
      parental feeding styles, stress, depression and mother's own eating behaviour)
      that have been found to be associated with the development of children's eating
      behaviours and risk of childhood obesity. These new linkages are based on studies
      that were not incorporated into the original UNICEF model, but suggest important
      implications for childhood obesity. In all, this narrative review offers
      important advancements to the scientific understanding of familial influences on
      children's eating behaviours and childhood obesity. 

PMID- 25588386
TI  - Efficacy of sustained combination therapy for at least 6 months with thiopurines
      and infliximab in patients with ulcerative colitis in clinical remission: a
      retrospective multicenter French experience.
AB  - BACKGROUND AND AIMS: Long-term benefits of combination therapy (combotherapy)
      with infliximab (IFX) and azathioprine (AZA) have been less studied in ulcerative
      colitis (UC) than in Crohn's disease. The aim of the present study was to
      determine UC disease activity in patients who received at least 6 months of
      combotherapy, and whether cotreatment for more than 6 months was useful in these
      patients. METHODS: A retrospective multicenter study was conducted in seven
      French academic centers from January 2010 to September 2012, including all UC
      patients having received at least 6 months of combotherapy in prolonged remission
      off steroids. During the follow-up period, which was divided into trimesters,
      scheduled IFX was continued as maintenance and AZA could be withdrawn. Assessment
      of UC activity by trimester was based on the following events: disease relapse
      defined by clinical relapse requiring a change of treatment, IFX failure, and
      colectomy. RESULTS: Eighty-two patients were included (mean age 38 years;
      male:female ratio 1:1) and followed up for a median of 22.3+/-14.0 months.
      Comparing 393 trimesters of combotherapy with 282 trimesters of IFX alone, fewer
      clinical relapses were observed with combotherapy (p = 0.049). Similar results
      were observed for IFX failure (p = 0.048). No difference was observed for
      colectomy. Duration of combotherapy longer than 9 months was inversely associated
      with clinical relapse (hazard ratio = 0.32 [95% confidence interval 0.15-0.70]).
      CONCLUSIONS: UC patients treated with combotherapy should maintain IFX and AZA
      for at least 9 months. Further studies are required to determine the optimal
      duration of combotherapy before stopping AZA in this situation.

PMID- 25588387
TI  - Better duplicate detection for systematic reviewers: evaluation of Systematic
      Review Assistant-Deduplication Module.
AB  - BACKGROUND: A major problem arising from searching across bibliographic databases
      is the retrieval of duplicate citations. Removing such duplicates is an essential
      task to ensure systematic reviewers do not waste time screening the same citation
      multiple times. Although reference management software use algorithms to remove
      duplicate records, this is only partially successful and necessitates removing
      the remaining duplicates manually. This time-consuming task leads to wasted
      resources. We sought to evaluate the effectiveness of a newly developed
      deduplication program against EndNote. METHODS: A literature search of 1,988
      citations was manually inspected and duplicate citations identified and coded to
      create a benchmark dataset. The Systematic Review Assistant-Deduplication Module
      (SRA-DM) was iteratively developed and tested using the benchmark dataset and
      compared with EndNote's default one step auto-deduplication process matching on
      ('author', 'year', 'title'). The accuracy of deduplication was reported by
      calculating the sensitivity and specificity. Further validation tests, with three
      additional benchmarked literature searches comprising a total of 4,563 citations
      were performed to determine the reliability of the SRA-DM algorithm. RESULTS: The
      sensitivity (84%) and specificity (100%) of the SRA-DM was superior to EndNote
      (sensitivity 51%, specificity 99.83%). Validation testing on three additional
      biomedical literature searches demonstrated that SRA-DM consistently achieved
      higher sensitivity than EndNote (90% vs 63%), (84% vs 73%) and (84% vs 64%).
      Furthermore, the specificity of SRA-DM was 100%, whereas the specificity of
      EndNote was imperfect (average 99.75%) with some unique records wrongly assigned
      as duplicates. Overall, there was a 42.86% increase in the number of duplicates
      records detected with SRA-DM compared with EndNote auto-deduplication.
      CONCLUSIONS: The Systematic Review Assistant-Deduplication Module offers users a
      reliable program to remove duplicate records with greater sensitivity and
      specificity than EndNote. This application will save researchers and information
      specialists time and avoid research waste. The deduplication program is freely
      available online.

PMID- 25588388
TI  - A flowering integrator, SOC1, affects stomatal opening in Arabidopsis thaliana.
AB  - Stomatal movements are regulated by multiple environmental signals. Recent
      investigations indicate that photoperiodic flowering components, such as CRY, GI,
      CO, FT and TSF, are expressed in guard cells and positively affect stomatal
      opening in Arabidopsis thaliana. Here we show that SOC1, which encodes a MADS box
      transcription factor and integrates multiple flowering signals, also exerts a
      positive effect on stomatal opening. FLC encodes a potent repressor of FT and
      SOC1, and FRI acts as an activator of FLC. Thus, we examined stomatal phenotypes
      in FRI-Col, which contains an active FRI allele of accession Sf-2 by
      introgression. We found higher expression of FLC and lower expression of FT, SOC1
      and TSF in guard cells from FRI-Col than in those from Col. Light-induced
      stomatal opening was significantly suppressed in FRI-Col. Interestingly,
      vernalization of FRI-Col partially restored light-induced stomatal opening,
      concomitant with a decrease of FLC and increase of FT, SOC1 and TSF. Furthermore,
      we observed the constitutive open-stomata phenotype in transgenic plants
      overexpressing SOC1-GFP (green fluorescent protein) in guard cells (SOC1-GFP
      overexpressor), and found that light-induced stomatal opening was significantly
      suppressed in a soc1 knockout mutant. RNA sequencing using epidermis from the
      SOC1-GFP overexpressor revealed that the expression levels of several genes
      involved in stomatal opening, such as BLUS1 and the plasma membrane H(+)-ATPases,
      were higher than those in background plants. From these results, we conclude that
      SOC1 is involved in the regulation of stomatal opening via transcriptional
      regulation in guard cells. 

PMID- 25588389
TI  - RNAi screening identifies the armadillo repeat-containing kinesins responsible
      for microtubule-dependent nuclear positioning in Physcomitrella patens.
AB  - Proper positioning of the nucleus is critical for the functioning of various
      cells. Actin and myosin have been shown to be crucial for the localization of the
      nucleus in plant cells, whereas microtubule (MT)-based mechanisms are commonly
      utilized in animal and fungal cells. In this study, we combined live cell
      microscopy with RNA interference (RNAi) screening or drug treatment and showed
      that MTs and a plant-specific motor protein, armadillo repeat-containing kinesin
      (kinesin-ARK), are required for nuclear positioning in the moss Physcomitrella
      patens. In tip-growing protonemal apical cells, the nucleus was translocated to
      the center of the cell after cell division in an MT-dependent manner. When
      kinesin-ARKs were knocked down using RNAi, the initial movement of the nucleus
      towards the center took place normally; however, before reaching the center, the
      nucleus was moved back to the basal edge of the cell. In intact (control) cells,
      MT bundles that are associated with kinesin-ARKs were frequently observed around
      the moving nucleus. In contrast, such MT bundles were not identified after
      kinesin-ARK down-regulation. An in vitro MT gliding assay showed that kinesin-ARK
      is a plus-end-directed motor protein. These results indicate that MTs and the MT
      based motor drive nuclear migration in the moss cells, thus showing a
      conservation of the mechanism underlying nuclear localization among plant, animal
      and fungal cells. 

PMID- 25588391
TI  - [The rat submandibular lymph node after introduction in mandibular bone defect
      ultipotent mesenchymal cells adsorbed on polyhydroxyalkanoate scaffold].
AB  - The reactions of rat regional lymph nodes, caused by implantation of the
      autologous multipotent mesenchymal stromal cells of a bone marrow origin
      (AMMSCBM) for acceleration of bone defect regeneration in bottom jaw experiment
      were studied by methods of fluorescent light microscopy. After introduction in an
      injury site of a bottom jaw bone of polyhydroxyalkanoate with adsorbed AMMSCBM
      with a transfected GFP gene the numerous large macrophages with a set of oval
      fluorescent inclusions in cytoplasm appear in lymph nodules of submandibular
      lymph nodes. The number of such macrophages increases within 2 weeks after
      operation, and further starts decreasing. Probably, entered via such way the
      AMMSCBM partially are phagocytized by macrophages. At destruction of the
      structures created from AMMSCBM, debris also are phagocytized by macrophages. In
      that and other case these macrophages appear in the germinative centers of lymph
      nodules in lymph nodes where initiation of immunity reactions against DNA and
      same GFP isn't excluded. 

PMID- 25588390
TI  - Impact and cost-effectiveness of chlamydia testing in Scotland: a mathematical
      modelling study.
AB  - BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection
      in Scotland, and is associated with potentially serious reproductive outcomes,
      including pelvic inflammatory disease (PID) and tubal factor infertility (TFI) in
      women. Chlamydia testing in Scotland is currently targeted towards symptomatic
      individuals, individuals at high risk of existing undetected infection, and young
      people. The cost-effectiveness of testing and treatment to prevent PID and TFI in
      Scotland is uncertain. METHODS: A compartmental deterministic dynamic model of
      chlamydia infection in 15-24 year olds in Scotland was developed. The model was
      used to estimate the impact of a change in testing strategy from baseline (16.8%
      overall testing coverage; 0.4 partners notified and tested/treated per treated
      positive index) on PID and TFI cases. Cost-effectiveness calculations informed by
      best-available estimates of the quality-adjusted life years (QALYs) lost due to
      PID and TFI were also performed. RESULTS: Increasing overall testing coverage by
      50% from baseline to 25.2% is estimated to result in 21% fewer cases in young
      women each year (PID: 703 fewer; TFI: 88 fewer). A 50% decrease to 8.4% would
      result in 20% more PID (669 additional) and TFI (84 additional) cases occurring
      annually. The cost per QALY gained of current testing activities compared to no
      testing is L40,034, which is above the L20,000-L30,000 cost-effectiveness
      threshold. However, calculations are hampered by lack of reliable data. Any
      increase in partner notification from baseline would be cost-effective
      (incremental cost per QALY gained for a partner notification efficacy of 1
      compared to baseline: L5,119), and would increase the cost-effectiveness of
      current testing strategy compared to no testing, with threshold cost
      effectiveness reached at a partner notification efficacy of 1.5. However, there
      is uncertainty in the extent to which partner notification is currently done, and
      hence the amount by which it could potentially be increased. CONCLUSIONS: Current
      chlamydia testing strategy in Scotland is not cost-effective under the
      conservative model assumptions applied. However, with better data enabling some
      of these assumptions to be relaxed, current coverage could be cost-effective.
      Meanwhile, increasing partner notification efficacy on its own would be a cost
      effective way of preventing PID and TFI from current strategy.

PMID- 25588392
TI  - [Comparative analysis of the various instrumental diagnostics methods to the
      assessment of tooth supporting structure].
AB  - The tooth resonance frequency method for periodontal condition diagnostics was
      compared with apparatus measurement of the tooth mobility in vivo. Tooth natural
      frequency and tooth mobility were correlated with clinical condition of tooth
      supporting structure. According to the condition of tooth supporting structure
      stability zones were indentified. The squared dependence between tooth natural
      frequency and the value of tooth mobility was revealed. The resonance frequency
      method is more exact for clinical assessment of periodontal tissues in comparison
      with instrumental measurement of the tooth mobility. 

PMID- 25588393
TI  - [The main aspects of the multidisciplinary dispensary dental care to elderly and
      senile population].
AB  - In the article presents the characteristics of the organization of dispensary
      work with patients older than 60 years. The main directions and objectives
      dispensary. The features of clinical supervision of dental patients belonging to
      the category of persons decreed by the elderly, senile age from the perspective
      of interaction professionals in a multidisciplinary clinic. 

PMID- 25588394
TI  - [Clinical efficiency of short and long-term adjuvant therapy of chronic
      periodontal disease with azithromycin].
AB  - The purpose of the study was to compare the clinical response to two regimes of
      azithromycin use in the complex of non-surgical periodontal therapy. After
      initial periodontal therapy of chronic generalized periodontitis (CGP), 60
      patients were randomly assigned to 3 groups. In group 2 and 3 azithromycin was
      administered: 500 mg 1 time per day, 3 days, and by 500 mg 1 time per day, 7
      days, followed by 500 mg 1 time per week for 12 weeks. Clinical indexes were
      record before treatment and after 1, 3, 6 and 12 months. After 3 months 13
      patients in group 1st had the exacerbation of CGP, and only 1 and 2 patients
      (p<0.05) in the 2nd and 3rd groups, respectively. After 12 months, significantly
      fewer patients on the 3rd group (as compared with the 1st (p=0.0015) and the 2nd
      (p=0.0040) had clinical exacerbation. Unscheduled visits were significantly less
      in the 3rd group as compared with the 1st (chi(2)=8.03; p=0.0046). The long-term
      adjunctive azithromycin results in a significantly clinical benefit of 80%
      patients for 1 year with satisfactory tolerance.

PMID- 25588395
TI  - [Identification of key markers of normal and pathogenic microbiota determining
      health of periodontium by NGS-sequencing 16S-rDNA libraries of periodontal
      swabs].
AB  - By using NGS-sequencing libraries of DNA from periodontal swabs with primers
      specific to V6 region of 16S rDNA prevalence of bacterial genera and species in
      periodontal microbiota of patients with aggressive periodontitis and healthy
      donors was analyzed. Six genera of putative periodontal protectors and eight
      periodontal pathogens were identified with respect to aggressive (but not
      chronic) periodontitis. Statistically relevant over-colonization by general
      Porphyromonas, Treponema, Synergistes, Tannerella, Filifactor, Ruminococcus,
      Parvimonas and Mycoplasma was found to be associated with the condition. From
      these, only three genera Porphyromonas, Treponema and Tannerella are
      traditionally considered as periodontal pathogens. Statistically confidential
      over-colonization by genus Veillonella was found in healthy patients. This genus
      should be considered as a relevant marker of a healthy periodontium. Genera
      Streptococcus, Bergeyella, Granulicatella, Kingella and Corynebacterium may be
      considered as putative periodontal protectors. Comparison of data of NGS
      sequencing and real-time PCR demonstrated a good agreement if different PCR
      efficiency using independent primer pairs is taken into account. 

PMID- 25588396
TI  - [Audiodiagnostics in examination of patients with internal TMJ derangement].
AB  - The aim of the study was to assess the efficacy of audiodiagnostics in
      dysfunctional TMJ disorders. Thirty-four patients were included in the study. The
      analysis of phonograms revealed correlation of adverse sound effects with varying
      degrees of internal TMJ-disorder seen by MRI imaging. The study results confirm
      the advantages of electronic registration of TMJ sound phenomena. 

PMID- 25588398
TI  - [Evaluation of changes in periodontal status of patients with diabetes mellitus
      type II in surgical in-patient department after using Parodontax Extra Fresh
      toothpaste].
AB  - Inflammatory periodontal disease in patients with type II diabetes mellitus are
      characterized by a more severe course. Properly organized oral hygiene can
      effectively prevent and treat inflammation of periodontal tissues. The choice of
      therapeutic-prophylactic toothpaste, as one of the main means of personal
      hygiene, is especially important in patients with diabetes in surgical in-patient
      department. The study revealed high need in dental care (90%) in 20 patients with
      diabetes mellitus type II admitted to purulent surgery unit. After a week of
      using toothpaste Parodontax Extra Fresh oral hygiene index improved 1.8 times and
      BOP index reduced twice-folds. Decrease of tissue swelling and tartar formation
      was also seen. 

PMID- 25588397
TI  - [New method of conduction anesthesia in the maxilla].
AB  - There was the research aimed at improving the effeciency of intraosseous
      anesthesia in the maxilla by blocking the infraorbital nerve conduction along its
      entire length. In the experimental part of the needle puncture defined place and
      character of the spreading of contrast medium into the upper jaw. In the clinical
      part of the study shows the advantages of the proposed method of intraosseous
      anesthesia. 

PMID- 25588399
TI  - [TMJ disc displacement as a cause of changes in facial skeletal morphology].
AB  - OBJECTIVE: To evaluate an efficiency of TMJ open disc repositioning surgery with
      use of bone anchors. MATERIAL AND METHODS: TMJ open disc repositioning surgery
      was indicated for patients with TMJ anterior disc displacement without reduction
      and skeletal class II or asymmetric forms of dysgnathia related to condyle
      resorption. Surgery was performed on 9 patients divided into two groups: the
      first one (5 patients) consisted of patients that were seeking help for bite
      problems, the second one (4 patients) consisted of patients with signs of TMJD,
      such as decreased mouth opening and pain in TMJ area. RESULTS: The first group
      patients underwent open disc repositioning and orthognathic surgery with
      counterclockwise rotation of occlusal plane. All the patients showed stability in
      skeletal and occlusal elements at 6 months follow-up period. The second group
      patients underwent disc-repositioning surgery only. In all the cases pain was
      completely eliminated but there was no sufficient improvement in MIO at 6 months
      follow-up period. Open TMJ disc repositioning surgery can be used for prevention
      of relapse after orthognathic surgery in patients with TMJ internal derangements
      such as anterior disc displacement without reduction.

PMID- 25588400
TI  - [Total excision of parotid salivary gland saving ramus of n. facialis in the case
      of pharyngeal processus tumor].
AB  - The article describes the method of surgical treatment of patients with huge
      tumors of pharyngeal processus of parotid gland saving ramus of n. facialis. The
      method allows avoiding mandibular osteotomy without relapse risk it supposes the
      total excision of the gland. 

PMID- 25588401
TI  - [Recurrent mixed parotid tumor localized in pharyngeal processus].
AB  - Tumors of pleomorhic adenoma parapharingeal space of the parotid gland amount for
      less than 20% of all salivary gland tumors. In most cases these tumors are
      benign, and pleomorphic (polymorphous) adenomas prevail among them (up to 80
      90%). The frequency of their malignization varies from 3.6 to 30%. Pleomorphic
      adenoma of parapharingeal space of the parotid gland was removed from patient S.,
      aged 23 years, in head and neck department of RROI. Tumors of superficial part of
      the parotid gland were removed from the patient 5 times during the last 10 years
      maintaining the integrity of the facial nerve. Each time the tumor was
      pleomorphic adenoma morphologically. After physical and x-ray (CT, MRI, MRI with
      angiography of neck vessels) examinations a tumor -- pleomorphic adenoma -- was
      removed with submandibular method. The control MRI check showed continued growth.
      Radiation therapy was prescribed, after which the pronounced therapeutic effect
      was noted. The patient has been observed for 8 months without recurrence.

PMID- 25588402
TI  - [Impact of various second-stage implant surgery methods on adjacent gingival
      tissues microcirculation].
AB  - The paper presents the rezults of laser doppler flowmetry (LDF) studies of
      microcirculation in gingival tissues around dental implants disclosed by
      different methods. Microhemodynamics in gingival tissues when using a scalpel
      recovered after 14 days, carbon dioxide laser -- 7 days and erbium laser -- 3
      days, which may be important in the choice of the operation tactics.

PMID- 25588403
TI  - [Comprehensive treatment of patient with class III malocclusion complicated by
      partial teeth absence].
AB  - The article presents the results of planning and comprehensive treatment of a
      patient with class III malocclusion complicated by partial teeth absence. Split
      osteotomy of the mandible improved the relationship of dental arches facilitating
      complete oral restorative rehabilitation with adequate functional load
      distribution and esthetic harmony. 

PMID- 25588404
TI  - Authors' response: Importance of defining loss of response before therapeutic
      drug monitoring.

PMID- 25588405
TI  - The natural course of serrated lesions: a difficult enigma to resolve.

PMID- 25588406
TI  - Small-molecule inhibitors prevent the genotoxic and protumoural effects induced
      by colibactin-producing bacteria.
AB  - OBJECTIVE: Colorectal cancers (CRCs) are frequently colonised by colibactin toxin
      producing Escherichia coli bacteria that induce DNA damage in host cells and
      exhibit protumoural activities. Our objective was to identify small molecules
      inhibiting the toxic effects induced by these colibactin-producing bacteria.
      DESIGN: A structural approach was adopted for the identification of a putative
      ligand for the ClbP enzyme involved in the synthesis of colibactin. Intestinal
      epithelial cells and a CRC mouse model were used to assess the activity of the
      selected compounds in vitro and in vivo. RESULTS: Docking experiments identified
      two boron-based compounds with computed ligand efficiency values (-0.8 and -0.9
      kcal/mol/atom) consistent with data expected for medicinal chemistry leads. The
      crystalline structure of ClbP in complex with the compounds confirmed that the
      compounds were binding to the active site of ClbP. The two compounds (2 mM)
      suppressed the genotoxic activity of colibactin-producing E coli both in vitro
      and in vivo. The mean degree of suppression of DNA damage for the most efficient
      compound was 98+/-2% (95% CI). This compound also prevented cell proliferation
      and colibactin-producing E coli-induced tumourigenesis in mice. In a CRC murine
      model colonised by colibactin-producing E coli, the number of tumours decreased
      by 3.5-fold in animals receiving the compound in drinking water (p<0.01).
      CONCLUSIONS: These results demonstrate that targeting colibactin production
      controls the genotoxic and protumoural effects induced by this toxin.

PMID- 25588407
TI  - Validation of AD-CSF-Index in Chinese patients with Alzheimer's disease and
      nondemented controls.
AB  - Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), especially
      Abeta42/t-tau and Abeta42/p-tau, showed high diagnostic sensitivities and
      specificities. But significant interassay and interlaboratory variabilities
      hinder the widespread clinical applications of CSF biomarkers. The objective of
      this study was to validate the diagnostic accuracy of AD-CSF-Index in our local
      Chinese patients with AD compared to nondemented controls. A total of 36
      patients, which included 24 patients with AD and 12 nondemented controls, were
      recruited. Chinese patients with AD showed higher mean AD-CSF-Indices than
      nondemented controls (AD = 1.25-1.3, normal = 0.62-0.63; P < .001). The AD-CSF
      indices have a high sensitivity and specificity of 86.4% to 90.9% and 83.3%,
      respectively, in differentiating patients with AD from nondemented controls.
      After selecting the patients with "pure AD" and "pure normal" controls, the AD
      CSF-indices have a high sensitivity and specificity of 94.1% and 90%,
      respectively, in differentiating patients with AD from nondemented controls. Most
      importantly, our AD-CSF-indices cutoff was highly similar to that reported in
      Western studies. 

PMID- 25588408
TI  - The effectiveness of reality orientation in the treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most frequent cause of dementia. This work aims
      to assess the effectiveness of reality orientation (RO), a traditional,
      extensively documented cognitive enhancement technique, when combined with
      acetylcholinesterase inhibitors in the treatment of AD. Fourteen patients with AD
      having mild to moderate dementia receiving standard treatment with donepezil were
      randomly assigned to control and treatment groups. Patients in the treatment
      group were submitted to weekly RO sessions for 6 months. Cognitive outcomes were
      assessed based on scores in the Consortium to Establish a Registry for
      Alzheimer's Disease (CERAD) neuropsychological battery and the Clock Drawing Test
      (CDT). Mean CERAD neuropsychological battery, Mini-Mental State Examination
      (MMSE), and CDT scores improved in the treatment group and worsened in the
      control group. A number of CERAD neuropsychological battery and MMSE scores were
      statistically significant. Our findings suggest that RO is a valuable long-term
      complementary intervention for dementia in AD. 

PMID- 25588409
TI  - Serum sEPCR levels are elevated in patients with Alzheimer's disease.
AB  - Blood-brain barrier impairment and endothelial cell dysfunction have both been
      implicated in the pathogenesis of Alzheimer's disease (AD). The presence of
      vascular risk factors is also known to increase the risk of AD. Soluble
      endothelial protein C receptor (sEPCR) should thus produce procoagulant and
      proinflammatory effects. Serum sEPCR levels have been found to be associated with
      several diseases. To date, no reports have been published regarding serum sEPCR
      levels in AD. In this study, we found that serum sEPCR levels were significantly
      increased in patients with AD when compared to control participants (P = .0005).
      There was no significant difference between patients with mild cognitive
      impairment (MCI) and healthy controls (P = .055) or between patients with AD and
      MCI (P = .054). Importantly, our results also indicate that the degree of
      cognitive impairment is significantly correlated with serum sEPCR levels in all
      patients and healthy controls. These findings suggest that serum sEPCR levels
      could be a potential candidate for a biomarker panel for AD diagnosis. 

PMID- 25588410
TI  - The midwifery initiated oral health-dental service protocol: an intervention to
      improve oral health outcomes for pregnant women.
AB  - BACKGROUND: Evidence is emerging that women's poor oral health and health
      practices during pregnancy are associated with poor oral health in their children
      and potentially an increased risk of pre-term or low-birth weight infants.
      METHODS/DESIGN: The Midwifery Initiated Oral Health-Dental Service (MIOH-DS)
      trial is a three arm multicentre randomised controlled trial which will recruit
      women from three metropolitan hospitals aimed at improving women's oral health
      and service access and indirectly reducing perinatal morbidity. All three arms of
      the trial will deliver oral health promotion material, although a midwife oral
      assessment and referral to private/public/health fund dental services pathway
      (Intervention Group 1) and the midwife oral assessment and referral to local free
      public dental services pathway (Intervention Group 2) will be compared to the
      control group of oral health promotional material only. Midwives will undergo
      specific oral health education and competency testing to undertake this novel
      intervention. DISCUSSION: This efficacy trial will promote a new partnership
      between midwives and dentists focused on enhancing the oral health of women and
      their infants. Should the intervention be found effective, this intervention,
      with existing on-line educational program for midwives, can be easily transferred
      into practice for large metropolitan health services within and beyond Australia.
      Further cost-benefit analysis is proposed to inform national health policy. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12612001271897.

PMID- 25588412
TI  - Does the prepotential truly reflect the activation preceding the development of
      ventricular arrhythmias?

PMID- 25588413
TI  - Volatile composition and aroma activity of guava puree before and after thermal
      and dense phase carbon dioxide treatments.
AB  - Volatiles from initially frozen, dense phase carbon dioxide (DPCD)- and thermally
      treated guava purees were isolated by solid phase microextraction (SPME),
      chromatographically separated and identified using a combination of gas
      chromatography-mass spectrometry (GC-MS), GC-olfactometry (GC-O), and GC-pulsed
      flame photometric detector (GC-PFPD, sulfur mode). Fifty-eight volatiles were
      identified using GC-MS consisting of: 6 aldehydes, 2 acids, 15 alcohols, 6
      ketones, 21 esters, and 8 terpenes. Eleven volatiles were newly identified in
      guava puree. Hexanal was the most abundant volatile in all 3 types of guava
      puree. Ten sulfur compounds were identified using GC-PFPD of which 3 possessed
      aroma activity and 3 were not previously reported in guava puree. Both treatments
      profoundly reduced total sulfur peak areas and produced different peak patterns
      compared to control. Thermal treatment reduced total sulfur peak area 47.9%
      compared to a loss of 34.7% with DPCD treatment. Twenty-six volatiles possessed
      aroma activity. (Z)-3-Hexenyl hexanoate was the major contributor to the aroma of
      the freshly thawed and DPCD-treated guava puree. DPCD treatment reduced total MS
      ion chromatogram (MS TIC) peak area 35% but produced a GC-O aroma profile very
      similar to control. Whereas thermal treatment reduced total TIC peak area only
      8.7% compared to control but produced a 35% loss in total GC-O peak intensities. 

PMID- 25588411
TI  - Concurrent occurrence of renal cell carcinoma with rhabdoid features in a married
      couple: a case report.
AB  - BACKGROUND: Renal cell carcinoma (RCC) with rhabdoid features is a rare histology
      and exhibits clinically aggressive behavior. We report a case of a married couple
      in whom RCC with rhabdoid features concurrently occurred. The rarity of this
      event suggests that environmental factors may contribute to the etiology of RCC
      with rhabdoid features. CASE PRESENTATION: A 76-year-old Japanese woman was
      diagnosed with a hypervascular mass in the right kidney and tumor thrombus
      extending into the right atrium by enhanced computed tomography (CT). She
      underwent radical nephrectomy and tumor thrombectomy following systemic therapy
      with the tyrosine kinase inhibitor sunitinib. The histological evaluation denoted
      clear cell RCC with rhabdoid features. The patient died of cancer 12 months
      postoperatively. A 76-year-old man, her husband, presented with gross hematuria 2
      weeks after his wife had undergone surgery. He had a long history of asbestos
      exposure. An abdominal CT scan revealed a hypervascular mass in the right kidney
      and tumor thrombus extending into the inferior vena cava. He also underwent
      radical nephrectomy and tumor thrombectomy. The histological evaluation also
      showed clear cell RCC with rhabdoid features. Bone metastasis occurred 12 months
      postoperatively, but he died of an unrelated cause 18 months after surgery.
      CONCLUSION: Concurrent occurrence of RCC with rhabdoid features may not to be
      coincidental. Although further studies are warranted, asbestos exposure may
      contribute to the etiology of clear cell RCC with rhabdoid features.

PMID- 25588414
TI  - Development and validation of a real-time PCR assay for the detection of
      anguillid herpesvirus 1.
AB  - Anguillid herpesvirus 1 (AngHV1) causes a haemorrhagic disease with increased
      mortality in wild and farmed European eel, Anguilla anguilla (L.) and Japanese
      eel Anguilla japonica, Temminck & Schlegel). Detection of AngHV1 is currently
      based on virus isolation in cell culture, antibody-based typing assays or
      conventional PCR. We developed, optimized and concisely validated a diagnostic
      TaqMan probe based real-time PCR assay for the detection of AngHV1. The primers
      and probe target AngHV1 open reading frame 57, encoding the capsid protease and
      scaffold protein. Compared to conventional PCR, the developed real-time PCR is
      faster, less labour-intensive and has a reduced risk of cross-contamination. The
      real-time PCR assay was shown to be analytically sensitive and specific and has a
      high repeatability, efficiency and r(2) -value. The diagnostic performance of the
      assay was determined by testing 10% w/v organ suspensions and virus cultures from
      wild and farmed European eels from the Netherlands by conventional and real-time
      PCR. The developed real-time PCR assay is a useful tool for the rapid and
      sensitive detection of AngHV1 in 10% w/v organ suspensions from wild and farmed
      European eels. 

PMID- 25588415
TI  - Race-ethnicity and gender differences in VA health care service utilization among
      U.S. veterans of recent conflicts.
AB  - OBJECTIVE: The purpose of this study was to compare health care utilization
      patterns by race-ethnicity and gender among veterans returning from Iraq and
      Afghanistan. METHODS: A retrospective analysis was conducted with records from
      U.S. service members and veterans returning from Iraq and Afghanistan who
      enrolled in health care through the Veterans Health Administration, who received
      a psychiatric diagnosis, and who had used primary or mental health outpatient
      care between October 7, 2001, and December 31, 2012 (N=309,050). Racial-ethnic
      minority groups were first collapsed together and compared with whites and then
      separated by racial-ethnic group. Gender was also tested as a moderator of
      utilization. RESULTS: Although rates of mental health outpatient care, primary
      care, and emergency service utilization were relatively similar for racial-ethnic
      minority groups and whites, minority groups were admitted to psychiatric
      inpatient care at lower rates than whites. When veterans were separately
      categorized by specific racial-ethnic groups, some differences in utilization
      rates emerged; most notably, only black and Hispanic men were admitted less
      frequently to psychiatric inpatient care, and male and female Asian/Pacific
      Islander veterans used emergency services less, than their white counterparts.
      Gender moderated the association between race-ethnicity and mental health
      outpatient use, such that American Indian and Hispanic women used mental health
      outpatient services less than white women, but American Indian and Hispanic men
      showed the opposite pattern. Furthermore, black men were more likely than white
      men to use mental health outpatient services, but there was no difference between
      these women. CONCLUSIONS: Although service utilization rates between minority
      groups and whites were similar when minority groups were combined, examination of
      utilization by racial-ethnic groups and by men and women separately yielded more
      robust findings.

PMID- 25588416
TI  - Evolution of general practitioners' preferences for antipsychotics in France,
      2003-2010.
AB  - OBJECTIVE: The study examined changes in French general practitioners' (GPs)
      antipsychotic preferences between 2003 and 2010, a period when evidence
      challenging the superiority and safety of second-generation antipsychotics was
      introduced. METHODS: Data from the IMS Health Disease Analyzer database for a
      cohort of 347 GPs (with 12 or more antipsychotic prescriptions in 2003 and in
      2010) were used. For each year and GP, preferred antipsychotic was defined as the
      drug most frequently prescribed at the patient level. Trends in mean number of
      prescriptions, preferred drug, and changes in preferred antipsychotic class were
      documented. RESULTS: The mean annual number of antipsychotic prescriptions
      increased over the period (p<.001). The percentage of GPs who preferred a second
      generation antipsychotic tripled, from 16% in 2003 to 50% in 2010. In 2010, 42%
      of GPs who preferred first-generation antipsychotics in 2003 had switched their
      preference to second-generation antipsychotics. CONCLUSIONS: GPs' preferences for
      antipsychotics changed dramatically between 2003 and 2010.

PMID- 25588417
TI  - The costs and benefits of reducing racial-ethnic disparities in mental health
      care.
AB  - OBJECTIVE: Previous studies have found that timely mental health treatment can
      result in savings in both mental health and general medical care expenditures.
      This study examined whether reducing racial-ethnic disparities in mental health
      care offsets costs of care. METHODS: Data were from a subsample of 6,206
      individuals with probable mental illness from the 2004-2010 Medical Expenditure
      Panel Survey (MEPS). First, disparities in mental health treatment were analyzed.
      Second, two-year panel data were used to determine the offset of year 1 mental
      health outpatient and pharmacy treatment on year 2 mental and general medical
      expenditures. Third, savings were estimated by combining results from steps 1 and
      2. RESULTS: Compared with whites, blacks and Latinos with year 1 outpatient
      mental health care spent less on inpatient and emergency general medical care in
      year 2. Latinos receiving mental health care in year 1 spent less than others on
      inpatient general medical care in year 2. Latinos taking psychotropic drugs in
      year 1 showed reductions in inpatient general medical care. Reducing racial
      ethnic disparities in mental health care and in psychotropic drug use led to
      savings in acute medical care expenditures. CONCLUSIONS: Savings in acute care
      expenditures resulting from eliminating disparities in racial-ethnic mental
      health care access were greater than costs in some but not all areas of acute
      mental health and general medical care. For blacks and Latinos, the potential
      savings from eliminating disparities in inpatient general medical expenditures
      are substantial (as much as $1 billion nationwide), suggesting that financial and
      equity considerations can be aligned when planning disparity reduction programs.

PMID- 25588419
TI  - Assessment of two different types of sample for the early detection and isolation
      of thermophilic Campylobacter in broiler farms.
AB  - In order to assess the optimal method for the early detection and isolation of
      thermophilic Campylobacter in broilers at farm level, two types of samples were
      compared: caecal contents obtained by necropsy and cloacal swabs transported in
      charcoal Amies medium. The study was conducted in five batches of broilers from
      five different farms, where weekly samples (caecal contents and cloacal swabs)
      from 30 birds were obtained. Samples were plated onto selective agar (modified
      charcoal cefoperazone desoxycholate agar, mCCDA) for Campylobacter isolation.
      Four out of five batches were positive for Campylobacter. No marked differences
      in sensitivity of both sample types were observed. However, a higher percentage
      of positive birds were detected when cloacal swabs were used. The results show
      that cloacal swab samples are adequate, and in some cases even better than caecal
      samples for the early detection of Campylobacter in broiler flocks at farm level.
      Also, this sample avoids sacrificing birds to test Campylobacter, which not only
      allows saving time in sample collection, transportation and processing at the
      laboratory, but also improves bird welfare and cost of sampling. 

PMID- 25588418
TI  - Duration of Untreated Psychosis in Community Treatment Settings in the United
      States.
AB  - OBJECTIVE: This study is the first to examine duration of untreated psychosis
      (DUP) among persons receiving care in community mental health centers in the
      United States. METHODS: Participants were 404 individuals (ages 15-40) who
      presented for treatment for first-episode psychosis at 34 nonacademic clinics in
      21 states. DUP and individual- and site-level variables were measured. RESULTS:
      Median DUP was 74 weeks (mean=193.5+/-262.2 weeks; 68% of participants had DUP of
      greater than six months). Correlates of longer DUP included earlier age at first
      psychotic symptoms, substance use disorder, positive and general symptom
      severity, poorer functioning, and referral from outpatient treatment settings.
      CONCLUSIONS: This study reported longer DUP than studies conducted in academic
      settings but found similar correlates of DUP. Reducing DUP in the United States
      will require examination of factors in treatment delay in local service settings
      and targeted strategies for closing gaps in pathways to specialty FEP care.

PMID- 25588420
TI  - Synthetic cannabinoid withdrawal: a new demand on detoxification services.
AB  - INTRODUCTION AND AIMS: Synthetic cannabinoid dependence and withdrawal are not
      well described in the literature. We aimed to report on the characteristics and
      treatment course of clients attending a detoxification service for support with
      synthetic cannabinoid withdrawal in Auckland, New Zealand. DESIGN AND METHODS: A
      retrospective audit of electronic and paper files for clients presenting for
      treatment in association with problematic synthetic cannabinoid use between May
      2013 and May 2014 was conducted. Demographic information, reported synthetic
      cannabinoid use, other substance use, reported adverse effects, withdrawal
      symptoms and treatment information were recorded using a piloted template.
      Descriptive statistics were used to summarise the characteristics of the audit
      sample. RESULTS: In the 12 month period, 47 people presented to detoxification
      services reporting problems withdrawing from synthetic cannabinoids. Twenty
      clients were admitted for medical management within an inpatient setting.
      Coexisting substance dependence apart from nicotine dependence was low. The most
      common withdrawal symptoms were agitation, irritability, anxiety and mood swings.
      Withdrawal symptoms were managed with diazepam and quetiapine. DISCUSSION AND
      CONCLUSIONS: The harm associated with use of synthetic cannabinoids has had a
      direct impact on the utilisation of specialist alcohol and drug services in
      Auckland, New Zealand. Many clients with synthetic cannabinoid withdrawal
      symptoms required intensive support including medication and admission to an
      inpatient detoxification unit. Clients withdrawing from synthetic cannabinoids
      were the third largest group of clients admitted to inpatient detoxification
      services in Auckland, New Zealand, between May 2013 and May 2014.

PMID- 25588421
TI  - When the light begins to fade.

PMID- 25588422
TI  - What influences doctors to work in rural locations?

PMID- 25588423
TI  - Childhood food allergy and anaphylaxis: an educational priority.

PMID- 25588424
TI  - Can Australia's clinical practice guidelines be trusted?

PMID- 25588426
TI  - What can we do to help Australians die the way they want to?

PMID- 25588427
TI  - Antenatal care for asylum seekers.

PMID- 25588428
TI  - Inappropriate pathology ordering and pathology stewardship.

PMID- 25588429
TI  - Ethical challenges for doctors working in immigration detention.

PMID- 25588430
TI  - Ethical challenges for doctors working in immigration detention.

PMID- 25588432
TI  - Rural emergency departments supplement general practice care.

PMID- 25588431
TI  - Ethical challenges for doctors working in immigration detention.

PMID- 25588434
TI  - The importance of surgeons teaching anatomy, especially by whole-body dissection.

PMID- 25588433
TI  - Reporting rural workforce outcomes of rural-based postgraduate vocational
      training.

PMID- 25588435
TI  - Cardiopulmonary arrest and mortality trends, and their association with rapid
      response system expansion.

PMID- 25588436
TI  - Cardiopulmonary arrest and mortality trends, and their association with rapid
      response system expansion.

PMID- 25588437
TI  - Cardiopulmonary arrest and mortality trends, and their association with rapid
      response system expansion.

PMID- 25588438
TI  - Renal replacement therapy associated with lithium nephrotoxicity in Australia.

PMID- 25588440
TI  - Preventing type 2 diabetes: scaling up to create a prevention system.
AB  - About 2 million Australians have prediabetes and are at high risk of developing
      type 2 diabetes. Type 2 diabetes is a fast-growing epidemic and the economic
      costs are estimated to be $14.6 billion per year in Australia. Strong evidence
      from randomised controlled trials shows type 2 diabetes can be prevented in up to
      58% of people at high risk, through structured lifestyle intervention. Good
      evidence and experience obtained from translational studies in Australia shows we
      can deliver effective community-based prevention programs. To be effective, a
      national strategy for prevention of type 2 diabetes should involve two concurrent
      approaches - a targeted approach aimed at those most at risk (ie, with
      prediabetes) combined with an environments, systems and behaviour approach for
      the entire population. Australia's current efforts in both these areas are not
      nationwide, not large scale and often not sustained. 

PMID- 25588439
TI  - Chronic suppurative lung disease and bronchiectasis in children and adults in
      Australia and New Zealand Thoracic Society of Australia and New Zealand
      guidelines.

PMID- 25588441
TI  - Comparing non-sterile to sterile gloves for minor surgery: a prospective
      randomised controlled non-inferiority trial.
AB  - OBJECTIVE: To compare the incidence of infection after minor surgery conducted
      using non-sterile clean boxed gloves with surgery conducted using sterile gloves.
      DESIGN: Prospective randomised controlled single-centre trial testing for non
      inferiority in infection rates. SETTING: Primary care regional centre,
      Queensland, Australia. PARTICIPANTS: Consecutive patients presenting to
      participating general practitioners for a minor skin excision, between 30 June
      2012 and 28 March 2013, were eligible to participate. INTERVENTION: The use of
      non-sterile clean boxed gloves was compared with normal treatment using sterile
      gloves in the control group. MAIN OUTCOME MEASURES: Wound infection, assessed at
      the time of removal of sutures, and other adverse events. RESULTS: Four hundred
      and ninety-three consecutive patients presenting for minor skin excisions were
      randomly allocated to the two treatment groups: non-sterile clean boxed gloves (n
      = 250) or sterile gloves (n = 243). Four hundred and seventy-eight patients
      contributed data for analysis (241 non-sterile, 237 sterile gloves). The
      incidence of infection in the non-sterile gloves group (8.7%; 95% CI, 4.9%-12.6%)
      was significantly non-inferior compared with the incidence in the control group
      (9.3%; 95% CI, 7.4%-11.1%). The two-sided 95% CI for the difference in infection
      rate (- 0.6%) was - 4.0% to 2.9%, and did not reach the predetermined margin of
      7% which had been assumed as the non-inferiority limit. RESULTS of the intention
      to-treat analysis were confirmed by per-protocol and sensitivity analyses. There
      were no important adverse effects. CONCLUSION: Our study suggests that in regard
      to wound infection, non-sterile clean boxed gloves are not inferior to sterile
      gloves for minor skin excisions in general practice. TRIAL REGISTRATION:
      ACTRN12612000698875.

PMID- 25588442
TI  - Estimating the current and future prevalence of atrial fibrillation in the
      Australian adult population.
AB  - OBJECTIVE: To estimate the current and future prevalence of atrial fibrillation
      (AF) in the Australian adult population according to age and sex. DESIGN:
      Application of international AF prevalence statistics to Australian adult
      population data (for people >= 55 years) to estimate population prevalence; use
      of population projections to estimate potential future prevalence of AF. MAIN
      OUTCOME MEASURES: Estimated prevalence of AF in 2014 and future prevalence
      projected to 2034. RESULTS: We estimated that at 30 June 2014 there would be
      328,562 cases of AF among people aged >= 55 years (a prevalence of 5.35%; 95% CI,
      3.79%-7.53%), comprising 174,986 men (prevalence, 5.97%; 95% CI, 4.11%-8.54%) and
      153,576 women (prevalence, 4.79%; 95% CI, 3.50%-6.60%). Without significant
      changes to the natural history of AF, by 2034 this figure is projected to rise to
      over 600,000 (prevalence, 6.39%; 95% CI, 4.56%-8.90%), with a prevalence of 7.22%
      among men (95% CI, 4.99%-10.28%) and 5.64% (95% CI, 4.18%-7.64%) among women. The
      greatest projected regional increase in prevalence between 2014 and 2034 is
      expected in Queensland, with a likely twofold increase (from 61,613 cases to
      123,142 cases), although New South Wales cases will remain predominant, with a
      1.7-fold increase (from 110 892 to 191 578). We also predicted that between 2014
      and 2034 the number of AF cases would double among older age groups (from 200 638
      to 414 377 individuals aged >= 75 years) and would increase 2.5-fold among men
      aged >= 85 years (from 29 370 to 71 582). CONCLUSIONS: These data are indicative
      of a largely underappreciated AF prevalence in Australia. They mandate a more
      systematic effort to both understand and respond to an evolving AF burden.

PMID- 25588444
TI  - Availability of highly sensitive troponin assays and acute coronary syndrome
      care: insights from the SNAPSHOT registry.
AB  - OBJECTIVES: To examine differences in care and inhospital course of patients with
      possible acute coronary syndrome (ACS) in Australia and New Zealand based on
      whether a highly sensitive (hs) troponin assay was used at the hospital to which
      they presented. DESIGN, SETTING AND PATIENTS: A snapshot study of consecutive
      patients presenting to hospitals in Australia and New Zealand from 14 to 27 May
      2012 with possible ACS. MAIN OUTCOME MEASURES: Rates of major adverse cardiac
      events (inhospital death, new or recurrent myocardial infarction, stroke, cardiac
      arrest or worsening heart failure); association between assay type and outcome
      (via propensity score matching and a generalised estimating equation [GEE];
      averages of the predicted outcomes among patients who were treated with and
      without the availability of an hs assay (via inverse probability-weighting [IPW]
      with regression-adjusted estimators). RESULTS: 4371 patients with possible ACS
      were admitted to 283 hospitals. Over half of the hospitals (156 [55%]) reported
      using the hs assay and most patients (2624 [60%]) had hs tests (P = 0.004). Use
      of the hs assay was independent of hospital coronary revascularisation
      capability. Patients tested with the hs assay had more non-invasive
      investigations (exercise tests, stress echocardiography, stress nuclear scans,
      and computed tomography coronary angiography) than those tested with the
      sensitive assay. However, there were no differences between the groups in rates
      of angiography or revascularisation. All adjusted analyses showed a consistently
      lower rate of inhospital events, including recurrent heart failure in patients
      for whom the hs assay was used (GEE odds ratio, 0.75; 95% CI, 0.60-0.94; P =
      0.014); IPW analysis showed a 2.3% absolute reduction in these events with the
      use of the hs assay (P = 0.018). CONCLUSION: Use of hs troponin testing of
      patients hospitalised with possible ACS was associated with an increased rate of
      non-invasive cardiac investigations and fewer inhospital adverse events.

PMID- 25588445
TI  - Determinants of rural practice: positive interaction between rural background and
      rural undergraduate training.
AB  - OBJECTIVE: To determine the role of rural background and years of rural clinical
      school training on subsequent rural clinical practice. DESIGN, SETTING AND
      PARTICIPANTS: Retrospective cohort study of University of Queensland (UQ) medical
      graduates who graduated during the period 2002-2011 (contacted via internet,
      telephone and mail, using information obtained from UQ, the Australian Health
      Practitioner Regulation Agency, and telephone directory and internet searches)
      who completed an online or hard copy questionnaire during the period December
      2012 to October 2013. MAIN OUTCOME MEASURE: Current clinical practice in a rural
      location. RESULTS: Of 1572 graduates to whom the questionnaire was sent, 754
      (48.0%) completed the questionnaire. Of the respondents, 236 (31.3%) had a rural
      background and 276 (36.6%) had attended the University of Queensland Rural
      Clinical School (UQRCS). Clinical practice location was rural for 18.8% (90/478)
      of UQ metropolitan clinical school attendees and 41.7% (115/276) of UQRCS
      attendees (P < 0.001). In the multivariate model with main effects, independent
      predictors of rural practice were (OR [95% CI]): UQRCS attendance for 1 year
      (1.84 [1.21-2.82]) or 2 years (2.71 [1.65-4.45]), rural background (2.30 [1.57
      3.36]), partner with rural background (3.08 [1.96-4.84]), being single (1.98
      [1.28-3.06]) and having a bonded scholarship (2.34 [1.37-3.98]). In the model
      with interaction between UQRCS attendance and rural background, independent
      predictors of rural practice were rural background and UQRCS attendance for 1
      year (4.44 [2.38-8.29]) or 2 years (7.09 [3.57-14.10]), partner with rural
      background (3.14 [1.99-4.96]), being single (2.02 [1.30-3.12]) and bonded
      scholarship (2.27 [1.32-3.90]). The effects of rural background and UQRCS
      attendance were duration dependent. CONCLUSIONS: This study strengthens evidence
      that, after adjusting for multiple confounders, a number of exposures are
      independent predictors of rural medical practice. The strong positive interaction
      between rural background and rural clinical school exposure, and the duration
      dependent relationships, could help inform policy changes aimed at enhancing the
      efficacy of Australia's rural clinical school program.

PMID- 25588446
TI  - Full medical program fees and medical student career intention.
AB  - OBJECTIVE: To explore the future career preferences of Commonwealth-supported
      place (CSP) and full-fee paying (FFP) medical students in Australia. DESIGN,
      SETTING AND PARTICIPANTS: Data from the Medical Schools Outcomes Database and
      Longitudinal Tracking (MSOD) Project exit questionnaire for CSP and FFP students
      who graduated between 2008 and 2011 were analysed using logistic regression. The
      influence of age, sex, marital status, rural background and fee-paying status on
      future career preference were explored. MAIN OUTCOME MEASURE: Future career
      preference (location and specialty) at graduation. RESULTS: Compared with CSP
      students, domestic FFP students were more likely to nominate as their first
      preference both urban locations (odds ratio [OR], 5.58; 95% CI, 2.04-15.26; P <
      0.001) and higher-income specialties (OR, 1.37; 95% CI, 1.07-1.75; P < 0.05), and
      less likely to nominate as their first preference in-need specialties (OR, 0.72;
      95% CI, 0.52-1.00; P < 0.05), specifically general practice (OR, 0.71; 95% CI,
      0.52-0.99; P < 0.05). There was a significant domestic FFP student by marital
      status interaction effect, such that domestic FFP students who were married or
      partnered on exit from medical school were more likely to prefer a rural location
      (OR, 0.64; 95% CI, 0.44-0.95; P < 0.05). Also, students who were married or
      partnered were less likely to select a one of the higher-income specialties as
      their first preference (OR, 0.77; 95% CI, 0.64-0.92; P < 0.01). A rural
      background increased preferences for rural location (OR, 0.18; 95% CI, 0.15-0.22;
      P < 0.001) and in-need specialties (OR, 1.28; 95% CI, 1.04-1.57; P < 0.05), and
      being older on entry to medical school also increased preferences for rural
      location (OR, 0.96; 95% CI, 0.95-0.98; P < 0.001) and in-need specialties (OR,
      1.03; 95% CI, 1.01-1.04; P < 0.01). International FFP students were more likely
      to prefer urban practice (OR, 1.79; 95% CI, 1.19-2.72; P < 0.01). CONCLUSION:
      Domestic FFP graduates are less likely to prefer careers in rural locations and
      in lower-paid and in-need specialties, particularly general practice. Current
      workforce implications might be minor, but if fees for CSP students increase or
      more FFP places become available, potential impacts on workforce distribution
      will need to be considered.

PMID- 25588447
TI  - Toxic epidermal necrolysis - an investigation to dye for?

PMID- 25588448
TI  - All about John.

PMID- 25588454
TI  - Fatigue in chronic liver disease: exploring the role of the autonomic nervous
      system.

PMID- 25588453
TI  - Unemployment, government healthcare spending, and cerebrovascular mortality,
      worldwide 1981-2009: an ecological study.
AB  - BACKGROUND: The global economic downturn has been associated with unemployment
      rises, reduced health spending, and worsened population health. This has raised
      the question of how economic variations affect health outcomes. AIM: We sought to
      determine the effect of changes in unemployment and government healthcare
      expenditure on cerebrovascular mortality globally. METHODS: Data were obtained
      from the World Bank and World Health Organization. Multivariate regression
      analysis was used to assess the effect of changes in unemployment and government
      healthcare expenditure on cerebrovascular mortality. Country-specific differences
      in infrastructure and demographics were controlled for. One- to five-year lag
      analyses and robustness checks were conducted. RESULTS: Across 99 countries
      worldwide, between 1981 and 2009, every 1% increase in unemployment was
      associated with a significant increase in cerebrovascular mortality (coefficient
      187, CI: 86.6-288, P = 0.0003). Every 1% rise in government healthcare
      expenditure, across both genders, was associated with significant decreases in
      cerebrovascular deaths (coefficient 869, CI: 383-1354, P = 0.0005). The
      association between unemployment and cerebrovascular mortality remained
      statistically significant for at least five years subsequent to the 1%
      unemployment rise, while the association between government healthcare
      expenditure and cerebrovascular mortality remained significant for two years.
      These relationships were both shown to be independent of changes in gross
      domestic product per capita, inflation, interest rates, urbanization, nutrition,
      education, and out-of-pocket spending. CONCLUSIONS: Rises in unemployment and
      reductions in government healthcare expenditure are associated with significant
      increases in cerebrovascular mortality globally. Clinicians may also need to
      consider unemployment as a possible risk factor for cerebrovascular disease
      mortality.

PMID- 25588455
TI  - Loss of an ecological baseline through the eradication of oyster reefs from
      coastal ecosystems and human memory.
AB  - Oyster reefs form over extensive areas and the diversity and productivity of
      sheltered coasts depend on them. Due to the relatively recent population growth
      of coastal settlements in Australia, we were able to evaluate the collapse and
      extirpation of native oyster reefs (Ostrea angasi) over the course of a
      commercial fishery. We used historical records to quantify commercial catch of O.
      angasi in southern Australia from early colonization, around 1836, to some of the
      last recorded catches in 1944 and used our estimates of catch and effort to map
      their past distribution and assess oyster abundance over 180 years. Significant
      declines in catch and effort occurred from 1886 to 1946 and no native oyster
      reefs occur today, but historically oyster reefs extended across more than 1,500
      km of coastline. That oyster reefs were characteristic of much of the coastline
      of South Australia from 1836 to 1910 appears not to be known because there is no
      contemporary consideration of their ecological and economic value. Based on the
      concept of a shifted baseline, we consider this contemporary state to reflect a
      collective, intergenerational amnesia. Our model of generational amnesia accounts
      for differences in intergenerational expectations of food, economic value, and
      ecosystem services of nearshore areas. An ecological system that once surrounded
      much of the coast and possibly the past presence of oyster reefs altogether may
      be forgotten and could not only undermine progress towards their recovery, but
      also reduce our expectations of these coastal ecosystems.

PMID- 25588456
TI  - L-dopa does not add to the success of high-intensity language training in
      aphasia.
AB  - PURPOSE: L-dopa has been shown to improve outcome of moderate-intensity language
      training after stroke in acute aphasia. Given the critical role of training
      intensity we probed the effect of l-dopa in combination with high-intensity
      language training in chronic post-stroke aphasia. METHODS: In this prospective,
      randomized, placebo-controlled, double-blind study, aphasia patients (>1 year
      post stroke) were administered 100/25 mg of l-dopa/carbidopa or placebo daily
      prior to four hours of language training for two weeks. Conditions were crossed
      over after a wash-out period of 4 weeks. RESULTS: An a-priori planned interim
      analysis (n = 10) showed that naming performance and verbal communication
      improved significantly and persistently for at least 6 months in every patient,
      but l-dopa had no incremental effect to intensive training. CONCLUSION: High
      intensity language training in chronic aphasia may take learning to a ceiling
      that precludes additive benefits from l-dopa. Effects of l-dopa on post-stroke
      recovery during less intense treatment in chronic aphasia remain to be evaluated.

PMID- 25588457
TI  - Early hyaluronate injection improves quality of life but not neural recovery in
      unilateral vocal fold paralysis: an open-label randomized controlled study.
AB  - PURPOSE: To investigate the neurologic and functional effect of intracordal
      hyaluronate injections in acute unilateral vocal fold paralysis (UVFP) in a
      randomized controlled trial. METHODS: In this open-label, randomized controlled
      study, 29 patients with UVFP were recruited within 6 months of their first
      outpatient visit and were randomized to receive either single hyaluronate
      injection (HI group) or conservative management (CM group). Quantitative
      laryngeal electromyography, videolaryngostroboscopy, UVFP-related quality of life
      (Voice Outcomes Survey, VOS), laboratory voice analysis, and health-related
      quality of life (SF-36) were evaluated at baseline, and at 1, 3 and 6 months post
      injection in the HI group, and at baseline and 6 months in the CM group. RESULTS:
      Improvements in most quality of life domains and other assessments were
      comparable between the HI and CM groups; however, the HI group had a greater
      improvement in the mental health domain of quality of life at the end of follow
      up. CONCLUSIONS: Early hyaluronate injection cannot improve nerve regeneration
      but can result in long-lasting improvements in patients' psychosocial well-being,
      thus highlighting the importance of early intervention for patients with UVFP.

PMID- 25588458
TI  - Cortical inhibition and excitation by bilateral transcranial alternating current
      stimulation.
AB  - PURPOSE: Transcranial electric stimulations (tES) with amplitude-modulated
      currents are promising tools to enhance neuromodulation effects. It is essential
      to select the correct cortical targets and inhibitory/excitatory protocols to
      reverse changes in specific networks. We aimed at assessing the dependence of
      cortical excitability changes on the current amplitude of 20 Hz transcranial
      alternating current stimulation (tACS) over the bilateral primary motor cortex.
      METHODS: We chose two amplitude ranges of the stimulations, around 25 MUA/cm2 and
      63 MUA/cm2 from peak to peak, with three values (at steps of about 2.5%) around
      each, to generate, respectively, inhibitory and excitatory effects of the primary
      motor cortex. We checked such changes online through transcranial magnetic
      stimulation (TMS)-induced motor evoked potentials (MEPs). RESULTS: Cortical
      excitability changes depended upon current density (p = 0.001). Low current
      densities decreased MEP amplitudes (inhibition) while high current densities
      increased them (excitation). CONCLUSIONS: tACS targeting bilateral homologous
      cortical areas can induce online inhibition or excitation as a function of the
      current density.

PMID- 25588459
TI  - An ischemic stroke model of nonhuman primates for remote lesion studies: a
      behavioral and neuroimaging investigation.
AB  - PURPOSE: We aimed to develop a nonhuman primate (NHP) stroke model for studies of
      secondary lesions in remote areas and to characterize its behavioral and
      neuroimaging features. METHODS: Monkeys were either subjected to middle cerebral
      artery occlusion (MCAO) distal to the M1 branch (n = 17) or sham operation (n =
      7). Neurological assessment and magnetic resonance imaging (MRI) were performed
      before and 1 week after operation. RESULTS: After MCAO, six monkeys showed
      occlusion of the distal M1 segment and infarcts predominantly in the cortical and
      subcortical regions, without hippocampal and thalamic involvement. They had
      obvious neurological deficits. The other 11 monkeys showed blockage of the main
      trunk of the MCA, with infarcts extending into the hippocampus and thalamus, but
      no substantia nigra involvement. Their infarct volume were larger and
      neurological deficits were more severe than those after distal M1 occlusion. All
      sham-operated monkeys displayed normal behavior; however, MRI revealed small
      infarcts in three animals. CONCLUSIONS: MCAO or even sham operations might cause
      cerebral infarction in NHPs. Therefore, neurological assessment should be
      combined with MRI for screening candidate stroke models. Our model is suitable
      for studying secondary damage in remote regions, including the thalamus,
      hippocampus, and substantia nigra, after stroke.

PMID- 25588460
TI  - Treatment with amnion-derived cellular cytokine solution (ACCS) induces
      persistent motor improvement and ameliorates neuroinflammation in a rat model of
      penetrating ballistic-like brain injury.
AB  - PURPOSE: The present work compared the behavioral outcomes of ACCS therapy
      delivered either intravenously (i.v.) or intracerebroventricularly (i.c.v.) after
      penetrating ballistic-like brain injury (PBBI). Histological markers for
      neuroinflammation and neurodegeneration were employed to investigate the
      potential therapeutic mechanism of ACCS. METHODS: Experiment-1, ACCS was
      administered either i.v. or i.c.v. for 1 week post-PBBI. Outcome metrics included
      behavioral (rotarod and Morris water maze) and gross morphological assessments.
      Experiment-2, rats received ACCS i.c.v for either 1 or 2 weeks post-PBBI. The
      inflammatory response was determined by immunohistochemistry for neutrophils and
      microglia reactivity. Neurodegeneration was visualized using silver staining.
      RESULTS: Both i.v. and i.c.v. delivery of ACCS improved motor outcome but failed
      to improve cognitive outcome or tissue sparing. Importantly, only i.c.v. ACCS
      treatment produced persistent motor improvements at a later endpoint. The i.c.v.
      ACCS treatment significantly reduced PBBI-induced increase in myeloperoxidase
      (MPO) and ionized calcium binding adaptor molecule 1 (Iba1) expression.
      Concomitant reduction of both Iba1 and silver staining were detected in corpus
      callosum with i.c.v. ACCS treatment. CONCLUSIONS: ACCS, as a treatment for TBI,
      showed promise with regard to functional (motor) recovery and demonstrated strong
      capability to modulate neuroinflammatory responses that may underline functional
      recovery. However, the majority of beneficial effects appear restricted to the
      i.c.v. route of ACCS delivery, which warrants future studies examining delivery
      routes (e.g. intranasal delivery) which are more clinically viable for the
      treatment of TBI.

PMID- 25588461
TI  - Can transcranial direct current stimulation be useful in differentiating
      unresponsive wakefulness syndrome from minimally conscious state patients?
AB  - PURPOSE: Disorders of consciousness (DOC) diagnosis relies on the presence or
      absence of purposeful motor responsiveness, which characterizes the minimally
      conscious state (MCS) and the unresponsive wakefulness syndrome (UWS),
      respectively. Functional neuroimaging studies have raised the question of
      possible residual conscious awareness also in clinically-defined UWS patients.
      The aim of our study was to identify electrophysiological parameters, by means of
      a transcranial magnetic stimulation approach, which might potentially express the
      presence of residual networks sustaining fragmentary behavioral patterns, even
      when no conscious behavior can be observed. METHODS: We enrolled 25 severe DOC
      patients, following post-anoxic or traumatic brain injury and 20 healthy
      individuals (HC) as control group. Baseline electrophysiological evaluation
      evidenced, in comparison to HC, a partial preservation of cortical effective
      connectivity and excitability in clinically defined MCS, whereas these components
      were absent in clinically defined UWS. Then, we applied an anodal transcranial
      direct current stimulation (a-tDCS) protocol over the orbitofrontal cortex.
      RESULT: a-tDCS was able to boost cortical connectivity and excitability in all
      HC, MCS, and to unmask such excitability/connectivity in some UWS patients.
      CONCLUSION: a-tDCS could be useful in identifying residual connectivity markers
      in clinically-defined UWS, who may lack of purposeful behavior as a result of a
      motor-output failure.

PMID- 25588462
TI  - Caspase-3 inhibitor Z-DEVD-FMK enhances retinal ganglion cell survival and vision
      restoration after rabbit traumatic optic nerve injury.
AB  - PURPOSE: Vision loss after traumatic optic nerve injury is considered
      irreversible because of the retrograde loss of retinal ganglion cells (RGCs)
      which undergo apoptosis. Because the second messenger caspase-3 plays a major
      role in apoptosis, we now evaluated the efficacy of the specific caspase-3
      inhibitor, Z-DEVD-FMK, in a rabbit model of fluid percussion injury (FPI) which
      mimics traumatic optic nerve injury in humans to enhance cell survival and
      improve vision. METHODS: Survival of RGCs and recovery of vision were studied
      using retinal morphological markers and visual evoked potentials (VEP),
      respectively. The FPI traumatized animals were treated in their right eye with a
      single intravitreal or peribulbar injection of Z-DEVD-FMK 30 min post-injury
      compared to 2% DMSO control injections in their left eye. RESULTS: Intravitreal Z
      DEVD-FMK, but not control injections, led to down-regulation of capase-3 and
      reduced, in a dose-dependent manner, RGCs apoptosis from 7 to 21 days post
      injury. These morphological improvements were accompanied by vision restoration
      as documented by VEP. The neuroprotection after intravitreal injection of Z-DEVD
      FMK was more effective than the peribulbar application. CONCLUSIONS: The caspase
      3 inhibitor Z-DEVD-FMK is neuroprotective by inhibiting RGCs apoptosis when
      injected 30 min after optic nerve damage and significantly promotes restoration
      of vision. A controlled clinical trial is now needed to evaluate the efficacy and
      safety of Z-DEVD-FMK in humans.

PMID- 25588463
TI  - Quercetin ameliorates hypobaric hypoxia-induced memory impairment through
      mitochondrial and neuron function adaptation via the PGC-1alpha pathway.
AB  - PURPOSE: Acute hypobaric hypoxia (HH) causes persistent cognitive impairment,
      affecting memory function specifically. Mitochondrial dysfunction and synaptic
      morphological change were the prominent pathological features of HH exposure on
      brain. Quercetin, a flavonoid found in fruits, vegetables, leaves and grains, is
      reported to prevent ischemia induced by neuronal injury. This study investigated
      the efficacy of quercetin to ameliorate HH-induced memory deficit. METHODS: Rats
      were exposed to HH equivalent to 5000 m for 7 days in a decompression chamber and
      received quercetin daily (50, 75 or 100 mg/kg.bw) via gavage during the period of
      exposure. Cognitive performance was assessed by the Morris water maze test. In
      vitro, the effect of quercetin was tested in hippocampus tissue. RESULTS:
      Quercetin, especially at 100 mg/kg.bw, significantly reduced HH-induced memory
      decline. Meanwhile, HH-induced hippocampus mitochondrial and synaptic lesions
      were ameliorated by quercetin. Furthermore, quercetin regulated the expression of
      sirtuin 1(Sirt1), PGC-1alpha, and the proteins related with mitochondrial
      biogenesis and dynamics. Moreover, quercetin increased expression of fibronectin
      type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic
      factor (BDNF), showing the PGC-1alpha/FNDC5/BNDF pathways might be involved in
      neuronal adaptation. CONCLUSIONS: The results suggest quercetin has prophylactic
      potential for amelioration of HH-induced memory impairment, which is associated
      with the mitochondrial and neuronal adaptation in hippocampus.

PMID- 25588464
TI  - Prefrontal cortex as a compensatory network in ataxic gait: a correlation study
      between cortical activity and gait parameters.
AB  - PURPOSE: To investigate whether prefrontal cortex (PFC) functioning during ataxic
      gait is linked to compensatory mechanisms or to the typical intra-subject
      variability of the ataxic gait. METHODS: Nineteen patients with chronic ataxia
      and fifteen healthy subjects were evaluated. The subjects were requested to walk
      along a straight distance of 10 meters while PFC oxygenation and gait parameters
      were assessed. PFC activity was evaluated by NIRO-200 while gait analysis was
      performed by the SMART-D500. To investigate the intra-subject variability of
      gait, we calculated the coefficient of multiple correlation (CMC) of the hip,
      knee and ankle kinematic waveforms furthermore, we evaluated the step width.
      RESULTS: We observed a positive correlation between PFC bilateral oxygenation
      changes and the step width (r = 0.54; p = 0.02 for the right PFC, and r = 0.50; p
      = 0.03 for the left PFC). No correlation was found between PFC activity and CMC
      of the hip, knee and ankle waveforms. CONCLUSIONS: Our results suggest that PFC
      activity is linked to gait compensatory mechanisms more than to the variability
      of the joint kinematic parameters caused by a defective cerebellar control.

PMID- 25588465
TI  - Association between pneumoconiosis and pulmonary emboli. A Nationwide Population
      Based Study in Taiwan.
AB  - Studies on the association between pneumoconiosis and deep-vein thrombosis (DVT)
      and pulmonary thromboembolism (PE) are few. This study was based on data obtained
      from the Taiwan National Health Insurance Database from 2000 to 2006, with a
      follow-up period extending to the end of 2011. We identified 3719 pneumoconiosis
      patients and 14876 non-pneumoconiosis patients who were selected by frequency
      matched based on sex, age, and the index year. We analysed the risks of DVT and
      PE by using Cox proportional hazards regression models by including sex, age, and
      CCI score. The risk of developing PE was 1.90-fold in the patients with
      pneumoconiosis compared with the comparison cohort after adjustments for age,
      sex, and CCI score. By contrast, we did not observe significant effect of
      pneumoconiosis on DVT. However, the cumulative incidence curves for DVT were
      similar in the pneumoconiosis patients and non-pneumoconiosis patients. The
      multiplicative increased risks of PE were significant in patients with
      pneumoconiosis and CCI score of one and more. In conclusion, physicians should
      include pneumoconiosis in evaluating pulmonary embolism risk. 

PMID- 25588466
TI  - Molecular and phenotypic characteristics of maturity-onset diabetes of the young
      compared with early onset type 2 diabetes in China.
AB  - BACKGROUND: The aim of the present study was to investigate the contribution of
      maturity-onset diabetes of the young (MODY) genes to the etiology of 14 Chinese
      MODY families and to assess phenotypic differences between patients with MODY but
      without a known genetic cause of diabetes (MODYX) and those with early onset type
      2 diabetes (T2D). METHODS: The study included 14 MODY probands from unrelated
      families and 59 patients (age of onset <=35 years) diagnosed as early onset T2D.
      A standard meal test and metabolic studies were performed to characterize the
      clinical features of all patients. All probands with MODY were analyzed for
      nucleotide variations in promoters, exons, and exon-intron boundaries of 13 known
      MODY genes by direct DNA sequencing. RESULTS: Mutations in 13 known MODY genes
      were not present in the 14 Chinese families and they were classified as MODYX.
      However, different polymorphisms were identified, with I27L (42.9%; 12/28) and
      S487N (46.4%; 13/28) of hepatocyte nuclear factor 4alpha (HNF1alpha/MODY3) being
      two most frequent polymorphisms. Two new polymorphisms, namely T412I and D504H,
      were detected in carboxyl ester lipase (CEL/MODY8). Compared with patients with
      early onset T2D, patients with MODYX were diagnosed with diabetes at a younger
      age (28.3 +/- 6.5 vs 24.3 +/- 6.5 years; P < 0.05) and had a lower body mass
      index (BMI; 28.3 +/- 6.1 vs 24.1 +/- 4.3 kg/m(2) ; P < 0.01) and homeostatic
      model assessment of beta-cell function (47.6 [22.2-89.4] vs 18.5 [6.5-33.7]; P <
      0.05). CONCLUSION: Herein we report on 14 Chinese families with MODYX and
      describe its phenotype. Compared with early onset T2D, MODYX is characterized by
      lower BMI and decreased insulin-secreting capacity.

PMID- 25588467
TI  - Heterogeneity of tremor mechanisms assessed by tremor-related cortical potential
      in mice.
AB  - BACKGROUND: Identifying a neural circuit mechanism that is differentially
      involved in tremor would aid in the diagnosis and cure of such cases. Here, we
      demonstrate that tremor-related cortical potential (TRCP) is differentially
      expressed in two different mouse models of tremor. RESULTS: Hybrid tremor
      analysis of harmaline-induced and genetic tremor in mice revealed that two
      authentic tremor frequencies for each type of tremor were conserved and showed an
      opposite dependence on CaV3.1 T-type Ca(2+) channels. Electroencephalogram
      recordings revealed that alpha1(-/-);alpha1G(-/-) mice double-null for the GABA
      receptor alpha1 subunit (Gabra1) and CaV3.1 T-type Ca(2+) channels (Cacna1g), in
      which the tremor caused by the absence of Gabra1 is potentiated by the absence of
      Cacna1g, showed a coherent TRCP that exhibited an onset that preceded the
      initiation of behavioral tremor by 3 ms. However, harmaline-induced tremor, which
      is known to be abolished by alpha1G(-/-), showed no TRCP. CONCLUSIONS: Our
      results demonstrate that the alpha1(-/-);alpha1G(-/-) double-knockout tremor
      model is useful for studying cortical mechanisms of tremor.

PMID- 25588468
TI  - Methods of a multi-faceted rapid knowledge synthesis project to inform the
      implementation of a new health service model: Collaborative Emergency Centres.
AB  - BACKGROUND: The aim of this rapid knowledge synthesis was to provide relevant
      research evidence to inform the implementation of a new health service in Nova
      Scotia, Canada: Collaborative Emergency Centres (CECs). CECs propose to deliver
      both primary and urgent care to rural populations where traditional delivery is a
      challenge. This paper reports on the methods used in a rapid knowledge synthesis
      project to provide timely evidence to policy makers about this novel healthcare
      delivery model. METHODS: We used a variety of methods, including a
      jurisdictional/scoping review, modified systematic review methodologies, and
      integrated knowledge translation. We scanned publicly available information about
      similar centres across our country to identify important components of CECs and
      CEC-type models to operationalize the definition of a CEC. We conducted
      literature searches in PubMed, CINAHL, and EMBASE, and in the grey literature, to
      identify evidence on the key structures and processes and effectiveness of CEC
      type models of care delivery. Our searches were limited to published systematic
      reviews. The research team facilitated two integrated knowledge translation
      workshops during the project to engage stakeholders, to refine the research goals
      and objectives, and to share interim and final results. Citations and included
      articles were categorized by whether they addressed the CEC model or component
      structures and processes. Data and key messages were extracted from these reviews
      to inform implementation. RESULTS: CEC-type models have limited peer-reviewed
      evidence available; no peer-reviewed studies on CECs as a standalone healthcare
      model were found. As a result, our evidence search and synthesis was revised to
      focus on core CEC-type structures and processes, prioritized through consensus
      methods with the stakeholder group, and resulted in provision of a meaningful
      evidence synthesis to help inform the development and implementation of CECs in
      Nova Scotia. CONCLUSIONS: A variety of methods and partnership with decision
      makers and stakeholders enabled the project to address the limitations in the
      evidence regarding CECs and meet the challenge of identifying the best available
      evidence in a transparent way to meet the needs of decision-makers in a short
      timeframe.

PMID- 25588469
TI  - Development, optimization, and single laboratory validation of an event-specific
      real-time PCR method for the detection and quantification of Golden Rice 2 using
      a novel taxon-specific assay.
AB  - In this study, we developed, optimized, and in-house validated a real-time PCR
      method for the event-specific detection and quantification of Golden Rice 2, a
      genetically modified rice with provitamin A in the grain. We optimized and
      evaluated the performance of the taxon (targeting rice Phospholipase D alpha2
      gene)- and event (targeting the 3' insert-to-plant DNA junction)-specific assays
      that compose the method as independent modules, using haploid genome equivalents
      as unit of measurement. We verified the specificity of the two real-time PCR
      assays and determined their dynamic range, limit of quantification, limit of
      detection, and robustness. We also confirmed that the taxon-specific DNA sequence
      is present in single copy in the rice genome and verified its stability of
      amplification across 132 rice varieties. A relative quantification experiment
      evidenced the correct performance of the two assays when used in combination. 

PMID- 25588470
TI  - Magnetic field switchable dry adhesives.
AB  - A magnetic field controllable dry adhesive device is manufactured. The normal
      adhesion force can be increased or decreased depending on the presence of an
      applied magnetic field. If the magnetic field is present during the entire normal
      adhesion test cycle which includes both applying a preloading force and measuring
      the pulloff pressure, a decrease in adhesion is observed when compared to when
      there is no applied magnetic field. Similarly, if the magnetic field is present
      only during the preload portion of the normal adhesion test cycle, a decrease in
      adhesion is observed because of an increased stiffness of the magnetically
      controlled dry adhesive device. When the applied magnetic field is present during
      only the pulloff portion of the normal adhesion test cycle, either an increase or
      a decrease in normal adhesion is observed depending on the direction of the
      applied magnetic field. 

PMID- 25588471
TI  - Beneficial effects of cannabinoid receptor type 2 (CB2R) in injured skeletal
      muscle post-contusion.
AB  - The aim of the current study was to investigate the effects of cannabinoid
      receptor type 2 (CB2R) on the repair process of injured skeletal muscle, which
      could potentially lay solid foundations as a novel target for curing muscular
      fibrosis in future. A standardized rat model of skeletal muscle contusion was
      established, where rats were treated with the CB2R agonist JWH-133 or antagonist
      AM-630. The in vivo results revealed that CB2R activation with JWH-133
      significantly diminished the fibrotic areas, down-regulated the mRNA levels of
      collagen type I/III and augmented the number of multinucleated regenerating
      myofibers in the injured zones. The reasons leading to the aforementioned results
      were directly attributable to decreased mRNA levels of TGF-beta1, FN-EIIIA and
      alpha-SMA, reduced accumulation of myofibroblasts, and concomitantly increased
      mRNA levels of matrix metalloproteinase-1/2. However, we observed contrasting
      changes in rats treated with the CB2R antagonist AM-630. These results revealed
      multiple effects of CB2R in systematically inhibiting fibrotic formation and
      improving muscle regeneration, alongside its potential for clinical application
      in patients with skeletal muscle injuries and diseases. 

PMID- 25588473
TI  - [The state of the regenerative activity of the tympanic membrane tissues and the
      results of myringoplasty at different time points of remission of experimental
      otitis media].
AB  - The objective of the present study was to estimate the regenerative potential of
      the tympanic membrane tissues in the early period of remission after experimental
      otitis media and evaluate the results of myringoplasty. The experiments were
      carried out using 23 outbred dogs exhibiting no signs of "spontaneous otitis".
      Experimental otitis media was induced in 20 animals using a Staphylococcus aureus
      strain as the pathogenic organism. The treatment of the experimental animals was
      started two weeks after the development of otitis and continued up to obtaining
      the "dry ear" condition. The animals were allocated to 4 groups depending on the
      time of myringoplasty. In the animals of group 1 myringoplasty was performed one
      week after remission, those of groups 2, 3, and 4 underwent myringoplasty two,
      three, and four weeks after the onset of remission respectively. The results of
      the study indicate that the first two weeks after the inflammatory process in the
      middle ear subsided are the optimal time for myringoplasty because the
      proliferative activity during this period amounts to its maximum which promotes
      the survival of the transplant and the closure of tympanic defects. 

PMID- 25588472
TI  - Modeling drug resistance in a conjoint normal-tumor setting.
AB  - BACKGROUND: In this paper, we modify our previously developed conjoint tumor
      normal cell model in order to make a distinction between tumor cells that are
      responsive to chemotherapy and those that may show resistance. RESULTS: Using
      this newly developed core model, the evolution of three cell types: normal,
      tumor, and drug-resistant tumor cells, is studied through a series of numerical
      simulations. In addition, we illustrate critical factors that cause different
      dynamical patterns for normal and tumor cells. Among these factors are the co
      dependency of the normal and tumor cells, the cells' response mechanism to a
      single or multiple chemotherapeutic treatment, the drug administration sequence,
      and the treatment starting time. CONCLUSION: The results provide us with a deeper
      understanding of the possible evolution of normal, drug-responsive, and drug
      resistant tumor cells during the cancer progression, which may contribute to
      improving the therapeutic strategies.

PMID- 25588474
TI  - [The emergency plastic reconstruction of the tympanic membrane defects of post
      traumatic and iatrogenic etiology with the application of the nanostructured
      bioplastic material].
AB  - The objective of the present study was to estimate the effectiveness of the
      application of the nanostructured bioplastic material for the plastic
      reconstruction of tympanic defects of post-traumatic and iatrogenic etiology. The
      authors report the results of the emergency plastic reconstruction of tympanic
      defects of post-traumatic and iatrogenic nature with the application of the
      nanostructured bioplastic material (giamatrix). The analysis of the results of
      the study prfovidd definitive evidence of the effectiveness of plastic
      reconstruction of tympanic defects with the application of the nanostructured
      bioplastic material. 

PMID- 25588475
TI  - [The application of the nanostructured bioplastic material for the plastic
      reconstruction of perforations in the nasal septum].
AB  - The objective of the present work was to estimate the effectiveness of the
      application of the nanostructured bioplastic material for the plastic
      reconstruction of perforations in the nasal septum. A total of 80 patients were
      recruited for the study. Half of them underwent plastic reconstruction of
      perforations in the nasal septum with the application of the nanostructured
      bioplastic material. Forty patients were treated using no biotransplants. The
      functional state of nasal cavity mucosa was evaluated before and after surgery.
      It is concluded that the nanostructured bioplastic material used in the present
      study ensures efficacious reconstruction of nasal septum integrity after plastic
      correction of septal perforations. 

PMID- 25588476
TI  - [Diagnostics of stylohyoid syndrome].
AB  - This study was designed with the purpose of improving diagnostics of stylohyoid
      syndrome. To this effect, 75 patients presenting with this condition were
      examined with the use of clinical, roengenological, ultrasound, and
      electrophysiological methods. A combination of the most frequent complaints and
      objective symptoms underlain by the common mechanisms has been identified. It is
      concluded that this combination may be used as a basis for diagnostics of the
      pathology being considered. 

PMID- 25588477
TI  - [The gender- and age-specific differences in the structure of the styloid
      processes of the temporal bone].
AB  - The objective of the present study was to elucidate the significance of the
      gender- and age-related alterations in the styloid processes of the temporal bone
      and their gender specific structural changes in the subjects aged above 35 years
      as the risk factors of the development of stylohyoid syndrome. A total of 72
      styloid processes were harvested from the corpses during post-mortem autopsy.
      Their fixed preparations were used to determine by means of digital
      radiovisiography specific structural features of the bone tissue, the thickness
      of the cortical layer, diameter of osteons and Haversian canals, the number of
      osteons per unit area. The data obtained from the subjects below and above 35
      years of age were compared. A distinctive morphological feature of styloid
      processes taken from adult people was the presence of residual embryonic
      cartilaginous tissue (in 40% of the observations) in which the processes of endo-
      and perihondral oteogenesis continued (15% of the cases). The elder subjects were
      characterized by the significantly decreased bone tissue density, reduced number
      of osteons and osteocytes whereas the diameters of Haversian canals increased.
      These changes were more pronounced in the women than in the men. It is concluded
      that the continued growth of styloid processes and the development of bone tissue
      osteopenia in the subjects older than 35 years may serve as the risk factors of
      stylohyoid syndrome. 

PMID- 25588478
TI  - [The evaluation of nasal obstruction during pregnancy and its influence on the
      quality of life of the women].
AB  - The objective of the present study was to identify peculiar features of nasal
      obstruction in the pregnant women and to evaluate parameters of the quality of
      life in the patients suffering from rhinitis in comparison with those having
      adequate nasal breathing. A total of 120 pregnant women were available for the
      examination The estimated variables included the quality of life, ciliary
      activity, results of rheoencehalography, and estradiol levels. The results of the
      study indicate that the quality of life in the pregnant women presenting with
      rhinitis and nasal obstruction depends on the estradiol level and changes in the
      rheoencephalograms. The severity of clinical symptoms of nasal obstruction
      increased in parallel to variations in the parameters of the mucociliary
      transport. 

PMID- 25588479
TI  - [Hearing disorders in the children presenting with chronic pyelonephritis].
AB  - The objective of the present study was to develop the criteria for early
      diagnostics of hearing disorders in the children presenting with chronic
      pyelonephritis. The study included 100 children of whom 37 (37%) suffered from
      the sensorineural hearing loss. The early manifestations of this disorder and the
      enhancement of the acoustic sensitivity threshold for the high frequencies in the
      range from 6,000 to 8,000 Hz were documented. The study has demonstrated the
      dependence of the severity of hearing loss on the duration and severity of
      chronic pyelonephritis. The criteria for early diagnostics of hearing disorders
      in the children presenting with chronic pyelonephritis were developed and
      recommended for the inclusion in the standard examination of the patients with
      pyelonephritis. 

PMID- 25588480
TI  - [Dynamic changes in the microbial contamination of the exudate and the mucous
      membrane from the tympanic cavity in the course of experimental staphylococcal
      otitis media].
AB  - The objective of the present study was to determine the relationships between
      characteristics of the microbial contamination of the pyogenic exudate and the
      mucous membrane from the tympanic cavity in the course of experimental
      suppurative otitis media caused by staphylococcal infection. The experiments were
      carried out on 29 rabbits showing no signs of "spontaneous" otitis. Experimental
      staphylococcal suppurative otitis was induced in 26 of these animals. The degree
      of microbial contamination of the mucous membrane from the tympanic cavity was
      expressed either in colony-forming units per swab (CFU/swab) or as the number of
      microbial cells per 1 mg of the tissue. It was shown that microbial contamination
      of the exudate and the mucous membrane from the tympanic cavity depended on the
      extent of the inflammatory process in the middle ear in the course of
      experimental staphylococcal otitis. The highest degree of contamination fell on
      the acute phase of middle ear inflammation. Staphylococci disappeared from the
      mucous membrane sooner than from the exudate. This difference can be attributed
      to the different activity of the tssue immunity factors. 

PMID- 25588481
TI  - [The comparative characteristic of the microflora species composition in the
      tympanic cavity, nasal mucous membrane and external ear mucosa in the course of
      experimental suppurative staphylococcal otitis].
AB  - The objective of the present work was to study the species composition of
      microflora in the suppurative exudate from the tympanic cavity in the course of
      development of experimental suppurative staphylococcal otitis and to identify the
      initial sites of migration of secondary pathogens. The experiments were carried
      out on 20 adult rabbits showing no signs of "spontaneous" otitis. Experimental
      staphylococcal suppurative otitis was induced in 17 of these animals. The
      microbiological study included isolation and identification of pure bacterial
      cultures with the use of the classical method. The initial sites of migration of
      secondary pathogens were detected from the results of comparison of the species
      composition of microflora in tympanic exudate and the mucous membrane of the
      nearest anatomical regions, such as the nasal cavity an external auditory canal.
      The data obtained indicate that suppurative exudate from the tympanic cavity is
      populated by polyflora containing secondary pathogens, besides the principal ones
      (Staphylococci). The large amounts of secondary pathogens penetrate into the
      tympanic cavity from the mucous membranes of the nasal cavity and nasopharynx. It
      is concluded that the rhinotubal system is the major pathway through which
      pathogenic microflora migrates into the middle ear. 

PMID- 25588482
TI  - [The role of neurobioregulation in the combined treatment of subjective
      tympanophonia and dizziness].
AB  - The objective of the present study was to evaluate the effectiveness of the
      biological control technologies applied in the framework of the combined
      treatment of the patients complaining of subjective tympanophonia and dizziness
      with concomitant changes in the psychoemotional status. It was shown that the
      disturbances in the psychoemotional sphere associated with complaints of
      subjective tympanophonia and dizziness took place in 81.4% of the patients
      included in the study although 17.2% of them had no signs of organic pathology in
      the central and peripheral regions of the auditory and vestibular apparatuses. It
      is concluded that the proposed therapeutic strategy can be recommended in the
      case of poor effectiveness of the medicamnetal treatment in the patients
      presenting with subjective tympanophonia and dizziness with concomitant changes
      in the psychoemotional status because it permits to eliminate clinical
      manifestations of the disease or reduce their severity. 

PMID- 25588483
TI  - [The biomechanical prerequisites for the preservation of stapedius muscle tendon
      during stapedoplasty].
AB  - The objective of the present biomechanical and clinical study was to evaluate the
      consequences of the preservation of stapedius muscle tendon during stapedoplasty.
      The biomechanical investigations included mathematical simulation with the
      construction of the model based on the kinematic approach. The comparative
      clinical study of the results of stapedoplasty carried out between 2001 and 2010
      involved 340 patients (77 men and 263 women) at the mean age of 48.18 years.
      Twenty patients underwent piston stapedoplasty by the method of Shi, 320 ones
      were treated by stapedoplasty with the preservation of stapedius muscle tendon.
      The state of speech hearing and the audiometric air-bone gap (ABG) were deduced
      from the audiograms. The biomechanical study demonstrated a significant increase
      in the range of the movements of the long crus of the incus, after the removal of
      the stapedius tendon muscle and the preservation in part of the acoustic reflex
      in case of tendon preservation. The preservation of the tendon partly dampened
      excessive sound vibrations. The clinical study revealed the improvement of speech
      hearing parameters throughout the three-year postoperative follow-up period; it
      was especially pronounced within the first year after surgery with the
      preservation of stapedius muscle tendon. The size of ABG at a the frequencies
      falling in the 0.5-1 kHz and 6-8 kHz ranges after surgery with the preservation
      of stapedius muscle tendon was smaller than after the removal of the tendon
      during the three-year follow-up (p<0.005). The difference was especially well
      apparent within the first year after stapedoplasty. The difference in this
      parameter between the interventions with the preservation of stapedius muscle
      tendon and with its removal was insignificant (p>0.05). 

PMID- 25588484
TI  - [The bacteriological aspects of post-implantation Highmore maxillary sinusitis].
AB  - The present publication was designed to summarize the results of the studies on
      etiopathogenesis of post-implantation Highmore maxillary sinusitis. The taxonomic
      evaluation of the microbial "paysage" of the rhinosinonasal sphere following
      maxillary intraosseous dental implantation is reported. The non-infectious
      dystrophic nature of this pathological condition was demonstrated. 

PMID- 25588486
TI  - [The combined application of thermography and local thermometry for diagnostics,
      prognostication, modeling, and evaluation of the effectiveness of the treatment
      of acute sinusitis].
AB  - The objective of the present work was to study the possibilities of the combined
      application of thermography and local thermometry for diagnostics of acute
      sinusitis, characteristic of dynamics of the clinical course of this pathology,
      and evaluation of the effectiveness of its treatment. The study included 23
      patients presenting with acute rhinosinusitis and 21 ones free from pathology of
      paranasal sinuses. Contact thermometry was performed with the use of the
      electronic thermometer applied to the anterior surface of the inferior turbinated
      bone. An infrared thermovision camera was employed to carry out thermographic
      measurements. The study demonstrated variations in endonasal and surface
      temperature under effect of the treatment. Positive dynamics of the patients'
      conditions was manifested as a drop of endonasal temperature and relatively
      constant surface temperature. A rise in the surface temperature was associated
      with the pathological process. In the patients showing slightly positive dynamics
      of the disease, the surface temperature on the side of the pathological process
      was lower than on the unaffected side. This difference was interpreted as an
      indication of the reduced microcirculatory activity in this region. It was
      hypothesized that dynamics of the inflammatory process is to a large extent
      determined by the character of blood circulation in the affected region. The
      authors conclude that the combined application of thermometry and thermography
      not only improves the quality of diagnostics of acute rhinosinusitis but also
      facilitates the evaluation of its dynamics and the effectiveness of the
      treatment. 

PMID- 25588485
TI  - [The influence of local and combined acute suppurative Highmore maxillary
      sinusitis on the serum lactoferrin and interleukin-8 levels in the children].
AB  - The objective of the present study was to estimate the influence of isolated and
      combined acute suppurative Highmore maxillary sinusitis on the serum lactoferrin
      (LF) and interleukin-8 (IL-8) levels in the children. A total of 70 children at
      the age varying from 4 to 15 years were available for the examination. Twenty of
      them constituted the control group, 29 presented with acute suppurative Highmore
      maxillary sinusitis, in 21 cildren this condition was combined with frontitis,
      ethmoiditis, otitis, and adenoiditis. Serum lactoferrin and interleukin-8 levels
      were measured by solid phase enzyme-linked immunoassay. It was shown that all the
      aforementioned forms of rhinosinusitis were associated with a significant
      increase of the serum LF level, an universal factor inactivating the propagation
      of bacterial, viral, and fungal pathogens. The level of IL-8 known to activate
      chemotaxis was increased only in the children presenting with combined forms of
      suppurative Highmore maxillary sinusitis. It is concluded that this difference
      can be used for the purpose of dufferential diagnostics of different forms of
      suppurative maxillary sinusitis. 

PMID- 25588487
TI  - [A case of the late complication of stapedoplasty].
AB  - The authors report a case of the late complication of stapedoplasty that
      developed 1.5 years after the otherwise successful surgical intervention.
      Computed tomography revealed the displacement of the stapedial prosthesis into
      the internal ear. Upon revision, the prosthesis was replaced by a shorter one.
      Intraoperatively, the vestibular manifestations underwent complete regression.
      The substantial improvement of hearing was documented in the postoperative
      period. 

PMID- 25588488
TI  - [Pharyngeal rhabdomyosarcoma].

PMID- 25588489
TI  - [Pyocele of the posterior cells of the ethmoidal labyrinth and sphenoidal sinus
      in the patient with the history of nasopharyngeal rhabdomyosarcoma].

PMID- 25588490
TI  - [The experience with the use of neuromedin preparations for the treatment of
      sensorineural impairment of hearing].
AB  - The objective of the present study was to evaluate the effectiveness of the
      application of neuromedin for the treatment of sensorineural loss of hearing of
      different etiology. A total of 230 patients at the age varying from 20 to 60
      years presenting with sensorineural impairment of hearing were available for the
      observation. Neuromedin was administered intramuscularly at 15 mg/day (1.5%
      solution at a dose of 1.0 ml) for 10 day; thereafter, the patients took 20 mg
      neuromedin tablets thrice daily during one month. The majority of the patients
      reported an improvement of hearing and speech intelligibility. Complete
      restoration of hearing was documented in certain patients presenting with acute
      sensorineural impairment of hearing. 

PMID- 25588491
TI  - [The role of tanakan in the improvement of the effectiveness of vestibular
      rehabilitation].
AB  - The objective of the present study was to estimate the influence of tanakan on
      the duration of the period needed to achieve vestibular compensation in the
      patients presenting with peripheral vestibular dizziness in the course of
      vestibular rehabilitation with the use of the post-urographic system. 72 patients
      at the age varying from 18 to 42 years (46 women and 26 men) suffering from
      peripheral vestibular dizziness were treated on an individual basis for the
      purpose of vestibular rehabilitation 3-5 times per week for a total period of 3-6
      weeks. 42 of the 72 patients comprising group 1 were given Tanakan for 3 months
      at a dose of 40 mg thrice daily, the remaining 30 patients (group 2) continued to
      receive the vasoactive treatment as prescribed by attending physicians of other
      medical and diagnostic centres (protocols of their treatment recommended at local
      medical facilities did not include tanakan therapy). It is concluded that the use
      of tanakan for the treatment of the patients presenting with peripheral
      vestibular dizziness accelerates vestibular compensation and reduces the time
      necessary to achieve vestibular rehabilitation. Moreover, the combined treatment
      with the application of tanakan makes it possible to decrease the medicamental
      loading. 

PMID- 25588492
TI  - [The comparative effectiveness of framycetin included in combined therapy of
      adenoiditis in the children].
AB  - The objective of the present study was to evaluate the effectiveness of
      framycetin included in combined therapy of adenoiditis in the children. The study
      involved 67 children at the mean age of 6.9+/-2.7 years. Group 1 was comprised of
      35 children given framycetin as topical therapy, the patients of group 2 were
      treated by the endonasal administration of a 2% silver proteinate solution. It
      was shown that the use of framycetin as a component of combined therapy of
      adenoiditis enhances the effectiveness of the treatment and compliance to therapy
      in comparison with the same parameters in the case of the application of
      traditional topical antibacterial preparations. 

PMID- 25588493
TI  - [The new approaches to the treatment of inflammatory pharyngeal pathology].
AB  - The authors present a detailed characteristic of various topical medications
      applied for the treatment of tonsillopharyngitis with special reference to non
      steroidal anti-inflammatory drugs. These data give evidence of the advantages of
      such preparations over other pharmaceutical products for the topical treatment.
      It is concluded that the application of topical anti-inflammatory preparations
      should be a major component of the treatment of inflammatory pharyngeal pathology
      regardless of its etiology, either viral or bacterial. 

PMID- 25588494
TI  - [Ciliary epithelium and topical decongestants: how to minimize the undesirable
      events?].
AB  - The objective of the present study was to evaluate the influence of the
      combination of 0.1% xylometazoline with seawater (Rinomaris, "Jadran", Croatia)
      on the state and functional activity of the ciliary epithelium of the nasal
      cavity. The results of the study confirm the safety of this treatment and the
      possibility of its application in routine clinical practice. 

PMID- 25588495
TI  - QSIM: quantitative structured illumination microscopy image processing in ImageJ.
AB  - BACKGROUND: Structured illumination microscopy has been extensively used in
      biological imaging due to its low cost and easy implementation. However, the lack
      of quantitative imaging capability limits its application in absolute irradiance
      measurements. METHOD: We have developed a quantitative structured illumination
      microscopy image processing algorithm (QSIM) as a plugin for the widely used
      ImageJ software. QSIM can work with the raw images acquired by a traditional
      structured illumination microscope and can quantitatively measure photon numbers,
      with noise estimates for both wide-field images and sectioned images. RESULTS AND
      CONCLUSION: We demonstrated the quantitative image processing capability of QSIM
      by imaging a mouse kidney section in 3D. The results show that QSIM can transform
      structured illumination microscopy from qualitative to quantitative, which is
      essential for demanding fluorescence imaging applications.

PMID- 25588496
TI  - An Anteroseptal Accessory Pathway in a Patient with Dextrocardia and Situs
      Inversus.

PMID- 25588497
TI  - Acute His-Bundle Injury Current during Permanent His-Bundle Pacing Predicts
      Excellent Pacing Outcomes.
AB  - INTRODUCTION: His-bundle (HB) pacing (P) is a physiological alternative to right
      ventricular pacing (RVP), but is technically challenging and limited by higher
      pacing thresholds. Myocardial injury current (IC) recorded during right
      ventricular lead placement implies good tissue contact and is associated with low
      pacing thresholds. IC at the HB has not been previously described. We
      hypothesized that HBIC during permanent HBP may be associated with lower pacing
      thresholds. METHODS: Permanent HBP was performed using Medtronic Select
      Secure(tm) (Medtronic Inc., Minneapolis, MN, USA) delivered via a fixed-curve
      (C315 His) sheath. HB electrogram (EGM) was recorded in a unipolar fashion from
      the lead tip. Presence or absence of HBIC was documented. HBP threshold, sensing,
      and impedances were recorded at implant, 2 weeks, 2 months, and 1 year. RESULTS:
      Sixty patients (age 72 +/- 15 years; male 55%, sick sinus syndrome 40%,
      atrioventricular block 60%, fluoroscopy duration 9.2 +/- 3.7 minutes) underwent
      successful permanent HBP. HBIC was recorded in 22 (37%) patients (group I). HBEGM
      without IC was recorded in the remaining 38 (63%) patients (group II). Pacing
      threshold at implant, 2 weeks, 2 months, and 1 year were significantly lower in
      group I (1.16 +/- 0.4 V; 1.18 +/- 0.5 V; 1.23 +/- 0.6 V; 1.3 +/- 0.6 V @ 0.5 ms)
      compared to group II (1.75 +/- 0.7 V; 1.82 +/- 0.8 V; 1.93 +/- 0.8 V; 1.98 +/-
      0.9 V @ 0.5 ms, P < 0.05), respectively. CONCLUSIONS: IC can be recorded at the
      HB during permanent HBP in 37% of patients. HBIC is associated with significantly
      lower pacing thresholds compared to patients in whom HBIC was not recorded. HBIC
      may be a marker for superior short-term HBP thresholds.

PMID- 25588498
TI  - Soluble epoxide hydrolase inhibitory activity of phenolic components from the
      rhizomes and roots of Gentiana scabra.
AB  - Two new (1 and 2) and seven known phenolic compounds were isolated from a
      methanol extract of the rhizomes and roots of Gentiana scabra. Their structures
      were identified by spectroscopic analysis and comparing with reported values. The
      inhibitory effects of each compound on soluble epoxide hydrolase (sEH) were
      evaluated. Among them, compounds 2, 6, and 9 potently inhibited sEH activity. 

PMID- 25588500
TI  - Dispersion in the presence of acetic acid or ammonia confers gliadin-like
      characteristics to the glutenin in wheat gluten.
AB  - Spray-dried gluten has unique properties and is commercially available in the
      food industry worldwide. In this study, we examined the viscoelastic properties
      of gluten powder prepared by dispersion in the presence of acetic acid or an
      ammonia solvent and then followed by lyophilization instead of a spray drying.
      Mixograph measurements showed that the acid- and ammonia-treated gluten powders
      had marked decreases in the time to peak dough resistance when compared with the
      control gluten powder. The integrals of the dough resistance and bandwidth for 3
      min after peak dough resistance decreased in both treated gluten powders. Similar
      phenomena were observed when gliadin was supplemented to gluten powders. Basic
      and acidic conditions were applied to the acid- and ammonia-treated gluten
      powders, respectively, and the viscoelastic behaviors were found to depend on the
      pH in the gluten dispersion just before lyophilization. These behaviors suggest
      that gluten may assume a reversible change in viscoelasticity by a fluctuation in
      pH during gluten dispersion. SDS-PAGE showed that the extractable proteins
      substantially increased in some polymeric glutenins including the low molecular
      weight-glutenin subunit (LMW-GS) when the ammonia-treated gluten powder was
      extracted with 70% ethanol. In contrast, the extractable proteins markedly
      increased in many polymeric glutenins including the high molecular weight
      glutenin subunit and/or the LMW-GS when the acid-treated gluten powder was
      extracted with 70% ethanol. It thus follows that the extractability of polymeric
      glutenin to ethanol increases similarly to gliadin when gluten is exposed to an
      acidic or a basic pH condition; therefore, glutenin adopts gliadin-like
      characteristics. 

PMID- 25588503
TI  - Predicting and setting conservation priorities for Bolivian mammals based on
      biological correlates of the risk of decline.
AB  - The recognition that growing proportions of species worldwide are endangered has
      led to the development of comparative analyses to elucidate why some species are
      more prone to extinction than others. Understanding factors and patterns of
      species vulnerability might provide an opportunity to develop proactive
      conservation strategies. Such comparative analyses are of special concern at
      national scales because this is the scale at which most conservation initiatives
      take place. We applied powerful ensemble learning models to test for biological
      correlates of the risk of decline among the Bolivian mammals to understand
      species vulnerability at a national scale and to predict the population trend for
      poorly known species. Risk of decline was nonrandomly distributed: higher
      proportions of large-sized taxa were under decline, whereas small-sized taxa were
      less vulnerable. Body mass, mode of life (i.e., aquatic, terrestrial, volant),
      geographic range size, litter size, home range, niche specialization, and
      reproductive potential were strongly associated with species vulnerability.
      Moreover, we found interacting and nonlinear effects of key traits on the risk of
      decline of mammals at a national scale. Our model predicted 35 data-deficient
      species in decline on the basis of their biological vulnerability, which should
      receive more attention in order to prevent their decline. Our results highlight
      the relevance of comparative analysis at relatively narrow geographical scales,
      reveal previously unknown factors related to species vulnerability, and offer
      species-by-species outcomes that can be used to identify targets for
      conservation, especially for insufficiently known species.

PMID- 25588502
TI  - The MAP kinase-interacting kinases regulate cell migration, vimentin expression
      and eIF4E/CYFIP1 binding.
AB  - The MAP kinase-interacting kinases (Mnk1 and Mnk2) are activated by ERK and are
      best known for phosphorylating the translation initiation factor eIF4E. Genetic
      knockout of the Mnks impaired the migration of embryonic fibroblasts both in two
      dimensional wound-healing experiments and in three-dimensional migration assays.
      Furthermore, a novel and selective Mnk inhibitor, Mnk-I1, which potently blocks
      eIF4E phosphorylation, blocked the migration of fibroblasts and cancer cells,
      without exerting 'off-target' effects on other signalling pathways such as Erk.
      Mnk-I1 or genetic knockout of the Mnks decreased the expression of vimentin, a
      marker of mesenchymal cells, without affecting vimentin mRNA levels. Vimentin
      protein levels were much lower in Mnk1/2-knockout cells than in controls,
      although mRNA levels were similar. Our data suggest that the Mnks regulate the
      translation of the vimentin mRNA and the stability of the vimentin protein.
      Inhibition or genetic knockout of the Mnks increased the binding of eIF4E to the
      cytoplasmic FMRP-interacting protein 1 (CYFIP1), which binds the fragile-X mental
      retardation protein, FMRP, a translational repressor. Since FMRP binds mRNAs for
      proteins involved in metastasis, the Mnk-dependent release of CYFIP1 from eIF4E
      is expected to release the repression of translation of FMRP-bound mRNAs,
      potentially providing a molecular mechanism for the control of cell migration by
      the Mnks. As Mnk1/2 are not essential for viability, inhibition of the Mnks may
      be a useful approach to tackling cancer metastasis, a key process contributing to
      mortality in cancer patients. 

PMID- 25588501
TI  - Mitochondrial Ca(2+) uptake by the voltage-dependent anion channel 2 regulates
      cardiac rhythmicity.
AB  - Tightly regulated Ca(2+) homeostasis is a prerequisite for proper cardiac
      function. To dissect the regulatory network of cardiac Ca(2+) handling, we
      performed a chemical suppressor screen on zebrafish tremblor embryos, which
      suffer from Ca(2+) extrusion defects. Efsevin was identified based on its potent
      activity to restore coordinated contractions in tremblor. We show that efsevin
      binds to VDAC2, potentiates mitochondrial Ca(2+) uptake and accelerates the
      transfer of Ca(2+) from intracellular stores into mitochondria. In
      cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca(2+)
      sparks and thereby inhibits Ca(2+) overload-induced erratic Ca(2+) waves and
      irregular contractions. We further show that overexpression of VDAC2
      recapitulates the suppressive effect of efsevin on tremblor embryos whereas VDAC2
      deficiency attenuates efsevin's rescue effect and that VDAC2 functions
      synergistically with MCU to suppress cardiac fibrillation in tremblor. Together,
      these findings demonstrate a critical modulatory role for VDAC2-dependent
      mitochondrial Ca(2+) uptake in the regulation of cardiac rhythmicity. 

PMID- 25588504
TI  - Day-by-day variation in affect, arousal and alcohol consumption in young adults.
AB  - INTRODUCTION AND AIMS: Alcohol consumption has a well-established relationship
      with mood, with higher positive and negative affect predicting alcohol use. More
      recently, researchers have explored whether alcohol consumption occurs as a
      response to affect variability as an attempt to self-medicate and stabilise
      affect. Studies have revealed a positive association between alcohol use and
      intra- and inter-individual affect variability in clinical and university student
      samples; however not much is known of this relationship among the general
      community. DESIGN AND METHODS: Ecological Momentary Assessment (EMA) methods were
      used to investigate the relationship between affect and arousal variability and
      alcohol use in 53 community volunteers. Participants self-reported affect and
      arousal at three to five randomly timed moments throughout the day, as well as
      every time they drank. RESULTS: On a day-to-day basis, higher positive affect was
      associated with increased alcohol consumption. When analyses were restricted to
      self-reported affect prior to alcohol consumption, only increased arousal and
      decreased variability in arousal predicted the likelihood of alcohol consumption.
      Mean level of arousal was associated with the extent of alcohol consumed.
      DISCUSSION AND CONCLUSIONS: In this moderate drinking sample day-to-day affect
      and arousal, and arousal variability, were associated with alcohol consumption.
      Analyses restricted to pre-drinking observations provide further evidence that
      self-medication accounts of alcohol consumption may explain drinking initiation
      but that the relationship between affect factors and drinking behaviour may
      change around the point of first drink.

PMID- 25588505
TI  - Developing the eCPP: adapting an evidence-based parent training program for
      digital delivery in primary care settings.
AB  - BACKGROUND: Developing innovative delivery methods is needed to overcome time and
      logistic barriers to in-person participation in evidence-based parent training
      (PT) programs. PURPOSE: The purpose of this paper is to (a) describe the
      systematic process for adapting an evidence-based group PT program (the Chicago
      Parent Program) to a tablet-based delivery format, (b) present the adapted
      program, and (c) discuss opportunities and challenges of adapting evidence-based
      programs for alternative delivery methods. METHODS: To ensure consistency with
      the original program and relevance to the intended program recipients, three
      groups-parents (n = 10), CPP developers (n = 3), and digital delivery experts-
      were engaged throughout the systematic steps of the delivery adaptation of the
      Chicago Parent Program (eCPP). Group meetings were used to identify the program's
      core components, develop the adaptation program model, assess potential
      mismatches for the new delivery context, and adapt the original program model and
      materials. RESULTS: The final eCPP is a six-module Internet-based intervention
      that includes: interactive activities, video examples and explanations of
      parenting strategies, reflection questions, assessment of parent knowledge with
      feedback, and module practice assignments. LINKING EVIDENCE TO ACTION: Developing
      innovative delivery approaches for evidenced-based interventions are promising to
      increase intervention sustainability and participant access and engagement. It is
      critical that these adaptations are systematic and developed with expert
      consultation and community input.

PMID- 25588508
TI  - The role of the lymphatic system in endometriosis: a comprehensive review of the
      literature.
AB  - Endometriosis is a benign gynecological disorder characterized by the presence of
      tissue resembling the endometrium in locations outside the uterus. The
      pathogenesis of endometriosis is still unknown; however, it is believed that the
      lymphatic system plays major roles in the development and progression of the
      disease. The lymphatic dissemination theory has been proposed to explain the
      presence of endometrial and/or endometriotic tissue in lymphatic vessels, lymph
      nodes, and rare sites, as well as high reoccurrence rates following treatment.
      Despite the importance of the lymphatic system in many aspects of endometriosis,
      there has been no previous thorough scientific update on its role in the disease.
      A review of scientific literature on the lymphatic system, lymphangiogenesis, and
      immunological changes associated with endometriosis was conducted.
      Lymphangiogenic potential is disturbed and lymphatic vessel density increased in
      the eutopic endometrium of women with endometriosis, likely promoting the entry
      of endometrial tissues into the lymphatic circulation. Endometriotic lesions and
      endometrial-like cells are present in uterine-draining nodes and various other
      pelvic lymph nodes. Immune responses are impaired in uterine-draining nodes,
      likely favoring the survival of endometrial cells and lesion establishment. In
      addition, lymphangiogenesis in endometriotic lesions may contribute to lesion
      growth and persistence, and promote the spread of endometrial cells to draining
      lymph nodes. The evidence reviewed in this paper supports the theory of lymphatic
      dissemination of endometriosis and highlights the roles of the lymphatic system
      in the pathogenesis and persistence of endometriosis. Understanding these roles
      is crucial for establishment of novel therapeutic approaches. 

PMID- 25588509
TI  - Roles of Toll-like receptors 2 and 4 in mediating experimental autoimmune
      orchitis induction in mice.
AB  - The mammalian testis is an immunoprivileged site where male germ cell antigens
      are immunologically tolerated under physiological conditions. However, some
      pathological conditions can disrupt the immunoprivileged status and induce
      autoimmune orchitis, an etiological factor of male infertility. Mechanisms
      underlying autoimmune orchitis induction are largely unknown. The present study
      investigated the roles of Toll-like receptor 2 (TLR2) and TLR4 in mediating the
      induction of experimental autoimmune orchitis (EAO) in mice after immunization
      with male germ cell antigens emulsified with complete Freund adjuvant. Wild-type
      mice developed severe EAO after three immunizations, which was characterized by
      leukocyte infiltration, autoantibody production, and impaired spermatogenesis.
      Tlr2 or Tlr4 deficient mice showed relatively low susceptibility to EAO induction
      compared with wild-type mice. Notably, Tlr2 and Tlr4 double knockout mice were
      almost completely protected from EAO induction. Moreover, we demonstrated that
      TLR2 was crucial in mediating autoantibody production in response to
      immunization. The results imply that TLR2 and TLR4 cooperatively mediate EAO
      induction. 

PMID- 25588511
TI  - Stroke incidence and case-fatality among Indigenous and non-Indigenous
      populations in the Northern Territory of Australia, 1999-2011.
AB  - BACKGROUND: Stroke is a leading cause of death and disability in Australia. The
      impact of stroke on the Australia Indigenous people is, however, unclear. AIM:
      This study describes hospital-based stroke incidence and case fatality in the
      Northern Territory population in Australia. METHODS: Retrospective study of
      Northern Territory residents with a first-ever stroke episode and case fatality
      among Northern Territory residents in 1999-2011. RESULTS: The rate ratio of age
      adjusted stroke incidence between Indigenous and non-Indigenous populations was
      2.8 for men and 2.7 for women, similar to those reported elsewhere in Australia.
      The rate ratio increased to 3.8 (95% confidence interval: 3.4-4.3) after
      adjusting for multiple risk factors. There was no change in annual incidence
      between 1999 and 2011 for either non-Indigenous (incidence rate ratio per year
      1.01, 95% confidence interval: 1.00-1.03) or Indigenous people (incidence rate
      ratio: 1.00, 95% confidence interval: 0.98-1.02), although incidence did increase
      for non-Indigenous people in the 15-39 year age group (incidence rate ratio:
      1.09, 95% confidence interval: 1.02-1.17) and for Indigenous people in the 40-64
      year age group (incidence rate ratio: 1.03, 95% confidence interva1.00-1.06). The
      case fatality rate decreased from 22% in 1999 to 12% in 2011. In-hospital deaths
      were more common among; older and Indigenous people, for those with other chronic
      diseases, and from haemorrhagic stroke compared with ischemic stroke.
      CONCLUSIONS: In the Northern Territory, as elsewhere in Australia, Indigenous
      Australians are more likely than other Australians to suffer a stroke. Lack of
      falling in incidence in the Northern Territory population highlights the
      importance for ongoing comprehensive primary and acute care in reducing risk
      factors and managing stroke patients.

PMID- 25588512
TI  - Innovations in scholarly publishing. Evolving trends in research communication in
      a digital age: examples from the BMJ.
AB  - As technology and communication evolve rapidly in this digital age, scholarly
      publishing is also undergoing a makeover to match the diverse needs of
      researchers and clinicians. The BMJ has been at the forefront of innovating the
      presentation of research to increase its readabillty and usefulness. This article
      presents some of recent formats used for research communication at the BMJ. 

PMID- 25588510
TI  - Progesterone-based intrauterine device use is associated with a thinner apical
      layer of the human ectocervical epithelium and a lower ZO-1 mRNA expression.
AB  - Currently, whether hormonal contraceptives affect male to female human
      immunodeficiency virus (HIV) transmission is being debated. In this study, we
      investigated whether the use of progesterone-based intrauterine devices (pIUDs)
      is associated with a thinning effect on the ectocervical squamous epithelium,
      down-regulation of epithelial junction proteins, and/or alteration of HIV target
      cell distribution in the human ectocervix. Ectocervical tissue biopsies from
      healthy premenopausal volunteers using pIUDs were collected and compared to
      biopsies obtained from two control groups, namely women using combined oral
      contraceptives (COCs) or who do not use hormonal contraceptives. In situ staining
      and image analysis were used to measure epithelial thickness and the presence of
      HIV receptors in tissue biopsies. Messenger RNA levels of epithelial junction
      markers were measured by quantitative PCR. The epithelial thickness displayed by
      women in the pIUD group was similar to those in the COC group, but significantly
      thinner as compared to women in the no hormonal contraceptive group. The thinner
      epithelial layer of the pIUD group was specific to the apical layer of the
      ectocervix. Furthermore, the pIUD group expressed significantly lower levels of
      the tight junction marker ZO-1 within the epithelium as compared to the COC
      group. Similar expression levels of HIV receptors and coreceptors CD4, CCR5, DC
      SIGN, and Langerin were observed in the three study groups. Thus, women using
      pIUD displayed a thinner apical layer of the ectocervical epithelium and reduced
      ZO-1 expression as compared to control groups. These data suggest that pIUD use
      may weaken the ectocervical epithelial barrier against invading pathogens,
      including HIV. 

PMID- 25588513
TI  - Case report: Cavitation of mesenteric lymph nodes as the presenting feature of
      coeliac disease.
AB  - Cystic cavitation of the lymph nodes associated with hyposplenism is a rare and
      under-recognised complication of coeliac disease. This report encompasses the
      clinical, radiological and pathological features of this condition, while
      demonstrating the pivotal role radiological imaging plays in achieving a clinical
      diagnosis. 

PMID- 25588514
TI  - Scoring systems for heparin-induced thrombocytopenia (HIT): whither now?

PMID- 25588515
TI  - Mechano-growth factor accelerates the proliferation and osteogenic
      differentiation of rabbit mesenchymal stem cells through the PI3K/AKT pathway.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) can differentiate into chondroblasts,
      adipocytes, or osteoblasts under appropriate stimulation. Mechano-growth factor
      (MGF) reportedly displays a neuroprotective effect in cerebral regions that were
      exposed to ischemia and is expressed in stromal cells of the eutopic endometrium
      and in glandular cells of the ectopic endometrium. RESULTS: This study sought to
      understand the potential involvement of phosphatidylinositol-3-kinase
      (PI3K)/protein kinase B (AKT) in MGF-induced growth of rabbit MSCs (rMSCs). We
      applied various concentrations of MGF to cultured rMSCs and observed the growth
      rate of the cells, the changes in the phosphorylation state of AKT and mammalian
      target of rapamycin (mTOR), and the expression levels of alkaline phosphatase and
      osteocalcin. We found that the growth and osteogenic differentiation of MGF
      induced rMSCs were promoted primarily by phosphorylated AKT, and that this
      phosphorylation, as well mTOR phosphorylation, was mediated by the MGF receptor.
      CONCLUSION: Our study suggests that MGF promotes the growth and osteogenic
      differentiation of rMSCs primarily through the PI3K/AKT pathway.

PMID- 25588516
TI  - An evaluation of methods used to teach quality improvement to undergraduate
      healthcare students to inform curriculum development within preregistration nurse
      education: a protocol for systematic review and narrative synthesis.
AB  - BACKGROUND: Despite criticism, quality improvement (QI) continues to drive
      political and educational priorities within health care. Until recently, QI
      educational interventions have varied, targeting mainly postgraduates, middle
      management and the medical profession. However, there is now consensus within the
      UK, USA and beyond to integrate QI explicitly into nurse education, and faculties
      may require redesign of their QI curriculum to achieve this. Whilst growth in QI
      preregistration nurse education is emerging, little empirical evidence exists to
      determine such effects. Furthermore, previous healthcare studies evaluating QI
      educational interventions lend little in the way of support and have instead been
      subject to criticism. They reveal methodological weakness such as no reporting of
      theoretical underpinnings, insufficient intervention description, poor evaluation
      methods, little clinical or patient impact and lack of sustainability. This study
      aims therefore to identify, evaluate and synthesise teaching methods used within
      the undergraduate population to aid development of QI curriculum within
      preregistration nurse education. METHODS/DESIGN: A systematic review of the
      literature will be conducted. Electronic databases, Cumulative Index to Nursing
      and Allied Health Literature (CINAHL), Psychological Information (PsychINFO),
      Education Resources Information Centre (ERIC), Medical Literature Analysis and
      Retrieval System Online (MEDLINE) and Applied Social Sciences Index and Abstracts
      (ASSIA), will be searched alongside reference list scanning and a grey literature
      search. Peer-reviewed studies from 2000-2014 will be identified using key terms
      quality improvement, education, curriculum, training, undergraduate, teaching
      methods, students and evaluation. Studies describing a QI themed educational
      intervention aimed at undergraduate healthcare students will be included and data
      extracted using a modified version of the Reporting of Primary Studies in
      Education (REPOSE) Guidelines. Studies will be judged for quality and relevance
      using the Evidence for Policy and Practice Information and Co-ordinating Centre's
      (EPPI) Weight of Evidence framework and a narrative synthesis of the findings
      provided. DISCUSSION: This study aims to identify, evaluate and synthesise the
      teaching methods used in quality improvement education for undergraduate
      healthcare students where currently this is lacking. This will enable nursing
      faculty to adopt the most effective methods when developing QI education within
      their curriculum. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42014013847.

PMID- 25588517
TI  - Acupuncture in the treatment of infantile colic.
AB  - Regarding the recently published review "Looking for new treatments of Infantile
      Colic" by Savino et al. we want to add that positive effects of acupuncture have
      been demonstrated to release pain and agitation and that acupuncture seems to be
      a safe treatment when performed by trained acupuncturists. Inconclusive results
      in the few published articles on the subject can be due to different acupuncture
      points, different insertion time, different needling methods, differences in the
      outcome variables, in how the crying was measured and insufficient sample sizes.
      Further research is needed on understanding the utility, safety, and
      effectiveness of acupuncture in infants with colic. 

PMID- 25588518
TI  - Crystal-site engineering control for the reduction of Eu(3+) to Eu(2+) in
      CaYAlO4: structure refinement and tunable emission properties.
AB  - In this article, Eu-activated CaYAlO4 aluminate phosphors were synthesized by a
      solid-state reaction. Under UV light excitation, characteristic red line emission
      of Eu(3+) was detected in the range of 570-650 nm. In addition, we introduced
      crystal-site engineering approach into the CaYAlO4 host through incorporation of
      Si(4+)-Ca(2+) to replace Al(3+)-Y(3+), which would shrink the AlO6 octahedrons,
      accompanied by the expansion of CaO9 polyhedron, and then enable the partial
      reduction of Eu(3+) to Eu(2+). The crystal structure and underlying mechanism
      have been clarified on the basis of the Rietveld refinement analysis. The PL
      spectra of Ca0.99+xY1-xAl1-xSixO4:Eu0.01 (x = 0-0.30) exhibit both green emission
      of Eu(2+) (4f(6)5d(1)-4f(7), broadband around 503 nm) and red-orange emission of
      Eu(3+) ((5)D0-(7)F1,2, 593 and 624 nm) under UV light excitation with a quantum
      yield of 38.5%. The CIE coordinates of Ca0.99+xY1-xAl1-xSixO4:Eu0.01 (x = 0-0.30)
      phosphors are regularly shifted from (0.482, 0.341) to (0.223, 0.457) with
      increasing x, which would expand the application of Eu. Furthermore, this
      investigation reveals the correlations of structure and property of luminescent
      materials, which would shed light on the development of novel phosphors suitable
      for lighting and display applications. 

PMID- 25588519
TI  - 5HTT is associated with the phenotype psychological flexibility: results from a
      randomized clinical trial.
AB  - Adaption to changing environments is evolutionarily advantageous. Studies that
      link genetic and phenotypic expression of flexible adjustment to one's context
      are largely lacking. In this study, we tested the importance of psychological
      flexibility, or goal-related context sensitivity, in an interaction between
      psychotherapy outcome for panic disorder with agoraphobia (PD/AG) and a genetic
      polymorphism. Given the established role of the 5HTT-LPR polymorphism in
      behavioral flexibility, we tested whether this polymorphism (short group vs. long
      group) impacted therapy response as a function of various endophenotypes (i.e.,
      psychological flexibility, panic, agoraphobic avoidance, and anxiety
      sensitivity). Patients with PD/AG were recruited from a large multicenter
      randomized controlled clinical trial on cognitive-behavioral therapy. Pre- to
      post-treatment changes by 5HTT polymorphism were analyzed. 5HTT polymorphism
      status differentiated pre- to post-treatment changes in the endophenotype
      psychological flexibility (effect size difference d = 0.4, p < 0.05), but none of
      the specific symptom-related endophenotypes consistently for both the intent-to
      treat sample (n = 228) and the treatment completers (n = 194). Based on the
      consistency of these findings with existing theory on behavioral flexibility, the
      specificity of the results across phenotypes, and the consistency of results
      across analyses (i.e., completer and intent to treat), we conclude that 5HTT
      polymorphism and the endophenotype psychological flexibility are important
      variables for the treatment of PD/AG. The endophenotype psychological flexibility
      may help bridge genetic and psychological literatures. Despite the limitation of
      the post hoc nature of these analyses, further study is clearly warranted.

PMID- 25588520
TI  - Circulating mitochondrial DNA content associated with the risk of liver
      cirrhosis: a nested case-control study.
AB  - BACKGROUND AND AIMS: Accumulating evidence has indicated that variations of
      mitochondrial DNA (mtDNA) content may affect the susceptibility to hepatocellular
      carcinoma (HCC). However, no study has been conducted to evaluate the association
      of circulating mtDNA content and the risk of liver cirrhosis, a leading cause of
      HCC. METHODS: We conducted a nested case-control study including 136 cirrhotic
      hepatitis B virus (HBV) cases and 136 frequency-matched non-cirrhotic HBV
      controls. We determined mtDNA content in serum DNA using quantitative real-time
      PCR and analyzed its association with cirrhosis risk. RESULTS: We found that
      cirrhotic HBV patients had significantly lower levels of mtDNA content than non
      cirrhotic HBV controls (P = 0.0184). Compared to patients with high mtDNA
      content, those with low mtDNA content had a 2.25-fold increased risk of cirrhosis
      [odds ratio (OR) 2.25, 95 % confidence interval (CI) 1.26-4.02]. This association
      exhibited a significant dose relationship as evidenced in both tertile and
      quartile analyses (P for trend = 0.0018 and 0.0008, respectively). Stratified
      analyses showed that the association was prominent in younger patients (P =
      0.0122), males (P = 0.0069), never smokers (P = 0.0063), never drinkers (P =
      0.0078), patients with a family history of HBV infection (P = 0.0062), and
      patients with low values of aspartate aminotransferase to platelet ratio index
      (APRI), a commonly used noninvasive marker for cirrhosis (P = 0.0109). Moreover,
      a joint effect was observed between low mtDNA content and high APRI values on
      cirrhosis risk (OR 24.07, 95 % CI 6.72-86.24). CONCLUSIONS: Low circulating mtDNA
      content may confer an increased cirrhosis risk in HBV patients. Further
      prospective studies are warranted to validate these findings and explore the
      clinical significance.

PMID- 25588522
TI  - Optofluidic ultrahigh-throughput detection of fluorescent drops.
AB  - This paper describes an optofluidic droplet interrogation device capable of
      counting fluorescent drops at a throughput of 254,000 drops per second. To our
      knowledge, this rate is the highest interrogation rate published thus far. Our
      device consists of 16 parallel microfluidic channels bonded directly to a filter
      coated two-dimensional Complementary Metal-Oxide-Semiconductor (CMOS) sensor
      array. Fluorescence signals emitted from the drops are collected by the sensor
      that forms the bottom of the channel. The proximity of the drops to the sensor
      facilitates efficient collection of fluorescence emission from the drops, and
      overcomes the trade-off between light collection efficiency and field of view in
      conventional microscopy. The interrogation rate of our device is currently
      limited by the acquisition speed of CMOS sensor, and is expected to increase
      further as high-speed sensors become increasingly available.

PMID- 25588521
TI  - Incontinence and parent-reported oppositional defiant disorder symptoms in young
      children--a population-based study.
AB  - BACKGROUND: Oppositional defiant disorder (ODD) and incontinence are common
      disorders of childhood. We have examined associations between ODD symptoms and
      incontinence in a representative sample of young children. METHODS: A
      questionnaire with seven questions referring to incontinence, eight DSM-IV items
      of ODD, 15 items of the Home Situations Questionnaire and six items regarding
      eating, drinking or toileting refusal was administered to the parents of 718
      children at school-entry from a defined geographical area at school-entry.
      RESULTS: Of the 718 6-year-old children included in the analysis, 8.2% had
      nocturnal enuresis (NE), 1.5% had daytime urinary incontinence (DUI) and 1.1% had
      faecal incontinence (FI). Significantly more boys than girls had NE (12 vs.
      4.3%). Overall, 6.7% of children had ODD symptoms. Rates of ODD symptoms were
      significantly higher in incontinent children (19.5%) than in continent children
      (5.2%), with the highest rate of ODD symptoms in children with DUI (36.4%).
      Children with incontinence (mean 6.1 episodes) or ODD symptoms (mean 8.4
      episodes) showed non-compliant behaviours in more problem situations than
      continent children (mean 4.5 episodes) or children without ODD symptoms (mean 4.5
      episodes). CONCLUSIONS: Incontinence and ODD are common comorbid disorders at
      school-entry age. Boys are more affected by both disorders. Children with DUI
      have the highest rate of ODD symptoms. As ODD symptoms affect many daily family
      situations, ODD needs to be diagnosed and treated in children with incontinence,
      as it can negatively affect compliance.

PMID- 25588523
TI  - Validity of the >=50% Response Threshold in Treatment With NASHA/Dx Injection
      Therapy for Fecal Incontinence.
AB  - OBJECTIVES: Many fecal incontinence (FI) studies define primary efficacy outcome
      as a decrease from baseline of >=50% in the number of FI episodes; this threshold
      has never been validated. We aimed to establish the validity and responsiveness
      of >=50% reduction in FI episodes (responder50) as the threshold indicative of
      clinically meaningful response. METHODS: Adults with a Cleveland Clinic Florida
      fecal incontinence score >=10 were randomized to receive nonanimal stabilized
      hyaluronic acid/dextranomer (NASHA/Dx) injection or sham treatment in a 6-month
      trial. Validity and responsiveness of the primary end point were evaluated post
      hoc. The data were compared using different thresholds for defining a responder
      for a number of end points. RESULTS: Data from 206 patients (NASHA/Dx, n=136;
      sham, n=70) were evaluated. Incremental patient response threshold increases
      showed that although the percentage of patients who achieved response decreased
      with increasing threshold, the difference between treatments remained significant
      up to an 80% response threshold (NASHA/Dx, 23%; sham, 10%; P=0.02). Response
      thresholds between 40% and 80% demonstrated evidence for convergent validity,
      with the strongest correlation with the number of FI episodes, the number of FI
      episodes when the patient was awake, and the number of FI-free days observed at
      >=40% and >=50% thresholds. Further examination of the responder50 threshold
      indicated that, regardless of treatment (NASHA/Dx or sham), responders performed
      significantly better than nonresponders on nearly all secondary efficacy end
      points. CONCLUSION: This study demonstrates the responsiveness, validity, and
      clinical applicability of the >=50% response threshold in clinical studies of
      patients with FI receiving treatment with NASHA/Dx.

PMID- 25588524
TI  - Effect of exclusive enteral nutrition on the microbiota of children with newly
      diagnosed Crohn's disease.
AB  - OBJECTIVES: Exclusive enteral nutrition (EEN) is commonly used to treat pediatric
      Crohn's disease (CD). Meta-analysis of pediatric studies that have compared the
      effect of EEN with other treatments have shown that EEN induces remission in up
      to 80-85% of patients. We aimed to gain a comprehensive understanding of the
      effect of EEN on the microbiota of CD patients. METHODS: We used 16S rRNA gene
      and whole-genome high throughout sequencing to determine changes in the fecal
      microbiota of five CD children, before, during, and after EEN therapy and
      compared this with five healthy controls. RESULTS: The microbial diversity
      observed in CD patients tended to be lower than that in controls (CD: 2.25+/
      0.24, controls: 2.75+/-0.14, P=0.11). In all CD patients, dysbiosis was observed
      prior to therapy. EEN therapy had a positive effect in all patients, with 80%
      going into remission. In some patients, the positive effect diminished following
      the conclusion of EEN therapy. Significantly, the number of operational taxonomic
      units (OTU) decreased dramatically upon starting EEN and this corresponded with
      CD remission. Recurrence of CD corresponded with an increase in OTUs. Six
      families within the Firmicutes were found to correlate with disease activity
      during and following EEN therapy, a finding that was confirmed by whole-genome
      high throughput sequencing. CONCLUSIONS: Our results demonstrate that EEN leads
      to common and patient-specific alterations in the microbiota of CD patients, a
      number of which correlate with disease activity.

PMID- 25588525
TI  - Asparagopsis armata and Sphaerococcus coronopifolius as a natural source of
      antimicrobial compounds.
AB  - Methanol, n-hexane and dichloromethane extracts of twelve marine macro-algae
      (Rhodophyta, Chlorophyta and Heterokontophyta divisions) from Peniche coast
      (Portugal) were evaluated for their antibacterial and antifungal activity. The
      antibacterial activity was evaluated by disc diffusion method against Bacillus
      subtilis (gram positive bacteria) and Escherichia coli (gram negative bacteria).
      Saccharomyces cerevisiae was used as a model for the antifungal activity by
      evaluating the growth inhibitory activity of the extracts. The high antibacterial
      activity was obtained by the Asparagopsis armata methanolic extract (10 mm-0.1
      mg/disc), followed by the Sphaerococcus coronopifolius n-hexane extract (8 mm-0.1
      mg/disc), and the Asparagopsis armata dichloromethane extract (12 mm-0.3 mg/disc)
      against Bacillus subtilis. There were no positive results against Escherichia
      coli. Sphaerococcus coronopifolius revealed high antifungal potential for n
      hexane (IC50 = 40.2 ug/ml), dichloromethane (IC50 = 78.9 ug/ml) and methanolic
      (IC50 = 55.18 ug/ml) extracts against Saccharomyces cerevisiae growth. The
      antifungal potency of the Sphaerococcus coronopifolius extracts was similar with
      the standard amphotericin B. Asparagopsis armata and Sphaerococcus coronopifolius
      reveal to be interesting sources of natural compounds with antimicrobial
      properties.

PMID- 25588527
TI  - Continuous removal of nonylphenol by versatile peroxidase in a two-stage membrane
      bioreactor.
AB  - The ligninolytic enzymes versatile peroxidase (VP) and manganese peroxidase (MnP)
      have been previously described as efficient oxidizers of the endocrine disrupting
      chemical (EDC) nonylphenol at high concentrations of the pollutant. Envisaging
      the application of an enzymatic technology as a tertiary treatment in wastewater
      treatment plants, it is important to design a continuous reactor that performs
      the efficient removal of nonylphenol under environmental conditions. In the
      present research, a two-stage membrane bioreactor based on the production and use
      of Mn(3+)-malonate (chemical oxidant) was applied. The bioreactor consisted of an
      enzymatic reactor (R1) for the production of Mn(3+)-malonate by VP, coupled to an
      oxidation reactor (R2), where the oxidation of nonylphenol by Mn(3+)-malonate
      took place. The production of Mn(3+)-malonate in R1 was maintained constant: 500
      700 MUM with minimal deactivation of the enzyme. The oxidation reactor attained
      nearly complete removal of nonylphenol, even at a hydraulic retention time (HRT)
      shorter than 20 min. The operation with real wastewater containing nonylphenol at
      environmental concentrations (454 nM) was also successful, with a nonylphenol
      removal of 99.5% at a rate of 0.73 MUM h(-1). Moreover, when the HRT of R2 was
      sharply reduced to 6.8 and 3.6 min, the removal of nonylphenol was maintained
      beyond 99%, which proves the feasibility of the system to remove the target
      compound present in a real effluent, even at very short HRTs.

PMID- 25588528
TI  - Effects of different biomass drying and lipid extraction methods on algal lipid
      yield, fatty acid profile, and biodiesel quality.
AB  - Three lipid extraction methods of hexane Soxhlet (Sox-Hex), Halim (HIP), and
      Bligh and Dyer (BD) were applied on freeze-dried (FD) and oven-dried (OD)
      Chlorella vulgaris biomass to evaluate their effects on lipid yield, fatty acid
      profile, and algal biodiesel quality. Among these three methods, HIP was the
      preferred one for C. vulgaris lipid recovery considering both extraction
      efficiency and solvent toxicity. It had the highest lipid yields of 20.0 and
      22.0% on FD and OD biomass, respectively, with corresponding neutral lipid yields
      of 14.8 and 12.7%. The lipid profiling analysis showed that palmitic, oleic,
      linoleic, and alpha-linolenic acids were the major fatty acids in the algal
      lipids, and there were no significant differences on the amount of these acids
      between different drying and extraction methods. Correlative models applied to
      the fatty acid profiles concluded that high contents of palmitic and oleic acids
      in algal lipids contributed to balancing the ratio of saturated and unsaturated
      fatty acids and led to a high-quality algal biodiesel.

PMID- 25588529
TI  - Isolation and molecular characterization of thermostable phytase from Bacillus
      subtilis (BSPhyARRMK33).
AB  - The thermostable phytase gene was isolated from Bacillus subtilis ARRMK33
      (BsPhyARRMK33). The gene has an ORF of 1152 bp and that encodes a protein of 383
      amino acids. Sequence analysis showed high homology with Bacillus sp. phytase
      proteins, but no similarity was found with other phytases. SDS-PAGE analysis
      exhibited a predicted molecular mass of 42 kDa. Homology modeling of BsPhyARRMK33
      protein based on Bacillus amyloliquefaciens crystal structure disclosed its beta
      propeller structure. BsPhyARRMK33 recombinant plasmid in pET-28a(+) was expressed
      in Rosetta gami B DE3 cells and the maximum phytase activity 15.3 U mg(-1)
      obtained. The enzyme exhibits high thermostability at various temperatures and
      broad pH ranges. The recombinant protein retained 74% of its original activity
      after incubation at 95  degrees C for 10 min. In the presence of Ca(2+), the
      recombinant phytase activity was maximal where as it was inhibited by EDTA. The
      optimal pH and temperature for the recombinant phytase activity is achieved at
      7.0 and 55  degrees C, respectively. Thermostable nature and wide range of pH are
      promising features of recombinant BsPhyARRMK33 protein that may be employed as an
      efficient alternative to commercially known phytases and thereby alleviate
      environmental eutrophication.

PMID- 25588530
TI  - New erythromycin derivatives enhance beta-lactam antibiotics against methicillin
      resistant Staphylococcus aureus.
AB  - Newly synthesized erythromycin derivatives were screened for synergy with
      oxacillin and other beta-lactam antibiotics against methicillin-resistant
      Staphylococcus aureus (MRSA). MRSA ATCC43300 and some clinically isolated MRSA
      were used. Several erythromycin derivatives were found to possess high synergism
      with oxacillin against MRSA. The newly synthesized erythromycin derivatives were
      also tested for their inhibitory effects against MRSA, either separately or in
      combination with oxacillin, using serial broth dilution, disc diffusion, Etest
      strips, growth curves and time-kill curves. A representative derivative, SIPI
      8294, could potentiate almost all beta-lactam antibiotics tested against the
      model strain MRSA ATCC43300 from 4 to 128 times and had synergism with oxacillin
      against 12 of 16 clinical isolates of MRSA under one-fourth of the minimum
      inhibitory concentration (MIC) of the compounds. This is the first report on the
      synergistic activity of these new erythromycin derivatives. These findings
      provide a new choice for the treatment of infection caused by MRSA and lead us to
      further study the synergistic mechanism. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study is the first report on the synergy of anti-MRSA between new
      erythromycin derivatives and beta-lactam antibiotics in vitro. The results show
      that although the erythromycin derivatives have poor anti-MRSA effects alone,
      they possess high synergism with oxacillin against MRSA ATCC43300 and clinically
      isolated MRSA. These novel compounds can significantly reduce the dosage of beta
      lactam antibiotics against MRSA, while this synergistic effect is different from
      the combination of beta-lactams and beta-lactamase inhibitors. The research may
      provide a new choice for the treatment of infection caused by MRSA and be useful
      to the research and development of new combination of medicines.

PMID- 25588531
TI  - Relationship between electrocardiographic characteristics of left bundle branch
      block and echocardiographic findings.
AB  - BACKGROUND: Complete left bundle branch block (CLBBB) is an electrocardiographic
      (ECG) dromotropic disorder seen in patients with various structural heart
      diseases and sometimes is associated with poor prognosis. Its presence confounds
      the application of standard ECG criteria for the diagnosis of left ventricular
      hypertrophy (LVH), myocardial infarction (MI) in the chronic phase, and
      pathologies that produce changes on ST-T segment. The aim of this investigation
      was to establish the relationship between CLBBB and cardiac structural
      abnormalities assessed by echocardiography. METHODS: This observational, cross
      sectional study included ECG with CLBBB from 101 patients who also had
      transthoracic echocardiogram (TTE) performed within 6 months. RESULTS: The
      prevalence of structural heart disease on TTE was 90%. No ECG criterion was
      useful to diagnose LVH since no relationship was observed between 9 different ECG
      signs and increased left ventricular mass index. QRS duration (p = 0.16) and left
      axis deviation (p = 0.09) were unrelated to reduced left ventricular ejection
      fraction (LVEF). Eight ECG signs proposed for the diagnosis of the chronic phase
      of MI demonstrated similar effectiveness, with high specificity and reduced
      sensitivity. CONCLUSIONS: CLBBB is associated with elevated prevalence of cardiac
      structural disease and hinders the application of common ECG criteria for the
      diagnosis of LVH, reduced LVEF, or chronic phase of MI. No ECG finding
      distinguished patients with structural heart disease from those with normal
      hearts. Electrocardiographic criteria for the diagnosis of MI in the chronic
      phase are useful when present, but when absent cannot rule it out.

PMID- 25588532
TI  - Predictors of mortality in patients hospitalized for congestive heart failure
      with left ventricular ejection fraction >= 40.
AB  - BACKGROUND: There are limited data regarding the predictors of mortality in
      patients with acute congestive heart failure (CHF) and left ventricular ejection
      fraction (LVEF) >= 40%. METHODS: We evaluated clinical characteristics, mortality
      and prognostic factors in a sample of consecutive patients hospitalized for CHF
      with LVEF >= 40%. Multivariable Cox regression models were developed to predict
      mortality using baseline clinical characteristics and echocardiographic
      variables. RESULTS: The study population consisted of 191 patients, mean age 70
      +/- 14.6 years (60% female) with average follow-up of 4.0 +/- 2.8 years.
      Cumulative 5-year mortality was 58% in the entire population and it was 59% in
      men and 57% in women (p = 0.411). In multivariable analyses, predictors of
      mortality were the following: blood urea nitrogen (BUN) > 25 mg/dL (HR = 1.77; p
      = 0.002); absence of hypertension (HR = 1.58; p = 0.032), left ventricular end
      diastolic dimension (LVEDD) <= 4.1 cm (HR = 1.73; p = 0.011) and LVEF <= 45% (HR
      = 1.69; p = 0.027). CONCLUSIONS: Patients hospitalized for heart failure with
      LVEF >= 40% have very high mortality. Absence of hypertension, elevated BUN and
      lower LVEF <= 45% indicate increased risk of short- and long-term mortality.
      Lower LVEDD is an independent predictor of mortality in heart failure patients
      with LVEF >= 40%.

PMID- 25588533
TI  - Cardioversion differences among first detected episode, paroxysmal, and
      persistent atrial fibrillation patients in the RHYTHM AF registry in Poland.
AB  - BACKGROUND: The aim of the publication is to show differences among patients with
      the first detected episode of atrial fibrillation (AF), paroxysmal, and
      persistent AF patients, for whom cardioversion was planned in the hospital
      setting in Poland. METHODS: We present an analysis of the Polish cohort of the
      multicenter, multinational RHYTHM-AF registry. Consecutive patients in the
      hospital setting, aged >= 18 years, with documented AF at the time of enrollment,
      and for whom cardioversion of AF is one of the planned therapeutic options were
      recruited. Follow-up data was collected 60 days after enrollment. RESULTS: Five
      hundred-and-one patients were recruited, 483 with a defined AF type: 88 - first
      detected, 191 paroxysmal, and 204 persistent AF. CHA2DS2VASc scores were not
      significantly different between the groups, while treatment with vitamin K
      antagonists (VKA) was significantly lower in paroxysmal AF group than in
      persistent AF patients. Primary electrical cardioversion was most commonly
      performed in patients with persistent AF (90.4%), while primary pharmacological
      cardioversion - in the first detected AF (80.0%) and paroxysmal AF patients
      (76.7%). During 2 months of follow-up, the rate of rehospitalization and
      complications was comparable among the groups. CONCLUSIONS: Despite their
      comparable CHA2DS2VASc scores, patients with persistent AF were more frequently
      treated with VKA antagonists than other groups. Recurrence of AF within 2 months
      after restoring sinus rhythm was present in about 25% of the patients, and the
      rate of complications was not different among the three groups.

PMID- 25588534
TI  - Perceived control as a predictor of cardiovascular disease mortality in Poland.
      The HAPIEE study.
AB  - BACKGROUND: Neither the development in methods of treatment of coronary heart
      disease nor the changes in exposure to main cardiovascular disease (CVD) risk
      factors do not fully explain the trends in CVD mortality in Poland. An influence
      of psychosocial factors is considered. The aims of the study were: (1) to assess
      the relationship between perceived control and the prevalence of classic CVD risk
      factors; (2) to assess the relationship between perceived control and the risk of
      death from all causes and from CVD. METHODS: A cohort study with 5-year follow-up
      was conducted. Random sample of 10,728 permanent residents of Krakow aged 45-69
      was examined. Perceived control was measured using a standard 11-item scale. The
      studied group was divided into four subgroups of people with very high, high,
      moderate, and low perceived control according to quartile values. Data on deaths
      and causes were obtained from the local register, death certificates and
      participants' families. An independent effect of perceived control on CVD
      mortality was assessed using Cox proportional hazards models. RESULTS: Low
      perceived control was strongly associated with a higher CVD mortality,
      independently of age, education, marital status, history of CVD, hypertension,
      hypercholesterolemia, smoking, body mass index, physical activity or diabetes in
      both men and women (HR 2.68, 95% CI 1.36-5.31 and HR 5.18, 95% CI 1.17-22.96,
      respectively). After adjustment for age, both in men and women, the highest risk
      of death from all causes was observed in persons with low perceived control.
      Further adjustment for covariates attenuated the relationship. CONCLUSIONS:
      Perceived control is a strong independent predictor of CVD mortality and may be
      considered a CVD risk factor in the Polish urban population.

PMID- 25588535
TI  - Hybrid model of cardiac rehabilitation in men and women after myocardial
      infarction.
AB  - BACKGROUND: A relatively new alternative for post-myocardial infarction (MI)
      patients' care is the hybrid cardiac rehabilitation (CR) consisting of ambulatory
      and home-based parts. The aim of the study was to compare the influence of CR on
      physical capacity, safety, adherence and return to work in post-MI male and
      female patients with preserved left ventricular systolic function, and to assess
      who benefited more from this model of trainings. METHODS: The study comprised 57
      men aged 54.5 +/- 7.5 years and 30 women aged 52.2 +/- 6.7 years after MI. All
      subjects underwent an 8-week training program consisting of 24 interval
      trainings. The first 10 trainings were conducted in an out-patient clinic, then
      both groups did their training at home with TeleECG monitoring. At the beginning
      and after trainings all patients underwent a symptom-limited exercise stress
      test. Assessment included results of exercise tests. Moreover, a comparative
      analysis of adherence and returning to work in post MI female and male patients
      was performed. RESULTS: We found that trainings led to a significant improvement
      in physical capacity in all patients based on exercise test. When the training
      effects were compared between men and women, no significant differences were
      observed. The percentage of patients returning to work was higher in men than in
      women (78.9% vs. 50%, p < 0.01). CONCLUSIONS: 1. Hybrid rehabilitation resulted
      in a comparable improvement in physical capacity in post-MI low-risk male and
      female patients. 2. Although hybrid rehabilitation facilitated patients'
      adherence to the training program, their return to work was significantly greater
      only in post-MI men.

PMID- 25588536
TI  - Assessment of the relationship between a narrow fragmented QRS complex and
      coronary slow flow.
AB  - BACKGROUND: The coronary slow flow (CSF) phenomenon is a delayed antegrade
      progression of contrast agent to the distal branch of a coronary artery in the
      absence of obstructive coronary artery disease (CAD). A narrow fragmented QRS
      (fQRS) has been reported as a significant predictor of sudden cardiac death in
      patients with idiopathic dilated cardiomyopathy. The present study aimed to
      investigate the relationship between a narrow fQRS on the admission
      electrocardiogram (ECG) and CSF on coronary angiography. METHODS: This study
      included 165 consecutive patients (112 CSF, 53 controls) who underwent first-time
      diagnostic conventional coronary angiography for suspected CAD. Coronary flow was
      quantified by thrombolysis in myocardial infarction (TIMI) frame count (TFC). The
      patients were divided into two groups according to the presence or absence of a
      narrow fQRS complex on the admission ECG. RESULTS: Forty four patients were in
      the fQRS group (mean age, 52.97 +/- 3.13 years). There was no difference between
      the two groups with respect to age, gender, body mass index, family history,
      hyperlipidemia, hypertension, or diabetes mellitus. The extent of CSF was
      significantly greater in the fQRS group compared to the non-fragmented group (p <
      0.001). A significant correlation was also found between mean TFC values and fQRS
      (p < 0.001). On multivariate analysis, only CSF (p = 0.03) was a significant
      independent predictor for narrow fQRS, after adjustment for other parameters.
      CONCLUSIONS: The narrow fQRS is a simple, inexpensive, and readily available
      noninvasive ECG parameter that may be a new potential indicator of myocardial
      damage in patients with CSF.

PMID- 25588537
TI  - High-frequency QRS analysis compared to conventional ST-segment analysis in
      patients with chest pain and normal ECG referred for exercise tolerance test.
AB  - BACKGROUND: The novel analysis of high-frequency QRS components (HFQRS-analysis)
      has been proposed in patients with chest pain (CP) and normal electrocardiography
      (ECG) referred for exercise tolerance test (ex-ECG). The aim of the study was to
      compare the diagnostic value of ex-ECG with ex-HFQRS-analysis. METHODS: Patients
      with CP and normal ECG, troponin, and echocardiography were considered. All
      patients underwent ex-ECG for conventional ST-segment-analysis and ex-HFQRS
      analysis. A decrease >= 50% of the HFQRS signal intensity recorded in at least 2
      contiguous leads was considered an index of ischemia, as ST-segment depression >=
      2 mm or >= 1 mm and CP on ex-ECG. Exclusion criteria were: QRS duration >= 120 ms
      and inability to exercise. End-point: The composite of coronary stenosis >= 70%
      or acute coronary syndrome, revascularization, cardiovascular death at 3-month
      follow-up. RESULTS: Three-hundred thirty-seven patients were enrolled (age 60 +/-
      15 years). The percent-age of age-adjusted maximal predicted heart rate was 89 +/
      10 beat per minute and the maximal systolic blood pressure was 169 +/- 23 mm Hg.
      Nineteen patients achieved the end-point. In multivariate analysis, both ex-ECG
      and ex-HFQRS were predictors of the end-point. The ex-HFQRS-analysis showed
      higher sensitivity (63% vs. 26%; p < 0.05), lower specificity (68% vs. 95%; p <
      0.001), and comparable negative predictive value (97% vs. 96%; p = 0.502) when
      compared to ex-ECG-analysis. Receiver operator characteristics analysis showed
      the incremental diagnostic value of HFQRS (area: 0.655, 95% CI 0.60-0.71) over
      conventional ex-ECG (0.608, CI 0.55-0.66) and CP score (0.530, CI 0.48-0.59),
      however without statistical significance in pairwise comparison by C-statistic.
      CONCLUSIONS: In patients with CP submitted to ex-ECG, the novel ex-HFQRS-analysis
      shows a valuable incremental diagnostic value over ST-segment-analysis.

PMID- 25588538
TI  - [Clinicopathological correlations at the vitreoretinal interface].
AB  - BACKGROUND: Clinicopathological studies of the vitreoretinal interface (VRI)
      improve our understanding of the pathogenesis of vitreal maculopathy, facilitate
      differential diagnoses and help to develop new treatment strategies. OBJECTIVE:
      The aim of the study was to provide a comprehensive overview on
      clinicopathological correlations of the VRI. METHODS: A semi-structured
      literature search was performed in the Medline and Embase databases for relevant
      original studies on clinicopathological correlations of vitreal maculopathy, in
      addition to the latest books and review articles. RESULTS: Age-related vitreous
      changes with persistent vitreomacular adhesions on the retinal surface promote
      cellular migration and proliferation onto the vitreal side of the internal
      limiting membrane (ILM), thereby cementing the vitreomacular adhesions and
      strengthening the traction forces on retinal layers. Cellular or fibrocellular
      proliferation at the vitreomacular interface can be seen in all vitreal
      maculopathies. Furthermore, vitreoschisis in the context of anomalous posterior
      vitreous detachment causes the presence of vitreous cortex collagen fibrils on
      the vitreal side of the ILM which is associated with epiretinal membrane
      formation. Glial cells, hyalocytes and myofibroblasts represent the major cell
      types in the epiretinal cell proliferation. Glial cells and hyalocytes are
      capable of transdifferentiation into myofibroblasts which possess strong
      contractive properties and are well known for the production of extracellular
      matrix components. CONCLUSION: Removing vitreomacular adhesions and vitreous
      cortex collagen fibrils from the retinal surface is most important for successful
      treatment. In cases with epiretinal cell proliferation, however, removal of the
      ILM during macular surgery is mandatory to avoid reproliferation and recurrence.
      Improving the detection of epiretinal cell proliferation and cell distribution in
      patient eyes by optical coherence tomography or by introduction of new
      technologies should be addressed in the future.

PMID- 25588539
TI  - Sex worker activism, feminist discourse and HIV in Bangladesh.
AB  - This paper explores the relationship between sex worker activism and HIV-related
      discourse in Bangladesh, relating recent developments in activism to the
      influence of feminist thought. Following their eviction in 1991 from brothels
      from red light areas, Bangladeshi sex workers started a social movement, at just
      about the same time that programmes started to work with sex workers to reduce
      the transmission of HIV. This paper argues that both sex worker activism and HIV
      prevention initiatives find impetus in feminist pro-sex-work perspectives, which
      place emphasis on individual and collective agency. However, by participating in
      these programmes, sex workers failed to contest the imagery of themselves as
      'vectors' of HIV. In this way, they were unwittingly complicit in reproducing
      their identity as 'polluting others'. Moreover, by focusing on individual
      behaviour and the agency of sex workers, HIV programmes ignored the fact that the
      'choices' made by sex workers are influenced by a wide range of structural and
      discursive factors, including gender norms and notions of bodily purity, which in
      turn have implications for the construction of HIV-related risk. 

PMID- 25588540
TI  - Laser-induced fluorescence of free diamondoid molecules.
AB  - We observe the fluorescence of pristine diamondoids in the gas phase, excited
      using narrow band ultraviolet laser light. The emission spectra show well-defined
      features, which can be attributed to transitions from the excited electronic
      state into different vibrational modes of the electronic ground state. We assign
      the normal modes responsible for the vibrational bands, and determine the
      geometry of the excited states. Calculations indicate that for large diamondoids,
      the spectral bands do not result from progressions of single modes, but rather
      from combination bands composed of a large number of Deltav = 1 transitions. The
      vibrational modes determining the spectral envelope can mainly be assigned to
      wagging and twisting modes of the surface atoms. We conclude that our theoretical
      approach accurately describes the photophysics in diamondoids and possibly other
      hydrocarbons in general. 

PMID- 25588541
TI  - Central mucoepidermoid carcinoma of the anterior region of the mandible: report
      of an unusual case and review of the literature.
AB  - INTRODUCTION: Central mucoepidermoid carcinoma is a rare lesion, whose exact
      pathogenesis is still not fully understood. Generally, it is more frequently
      encountered in the mandible than in the maxilla and in the posterior than in the
      anterior aspect of the jaws. Cases of central mucoepidermoid carcinomas are
      rarely mentioned in the literature, and therefore, additional information
      concerning this type of lesion is needed. CASE REPORT: In the present paper, we
      report an extremely unusual case of a central mucoepidermoid carcinoma in the
      anterior region of the mandible of a 37-year-old female patient. The diagnosis
      and the surgical management of the tumor along with the reconstructive techniques
      utilized to restore the mandible and a 6-year follow-up are discussed.
      DISCUSSION: Central mucoepidermoid carcinoma is an unusual tumor of the jaws,
      especially in the anterior region. It is only locally aggressive and has most
      frequently a good prognosis if treated with wide surgical excision.

PMID- 25588543
TI  - 'Social, innovative and smart cities are happy and resilient': insights from the
      WHO EURO 2014 International Healthy Cities Conference.
AB  - This paper provides a brief overview of, and elaborates on, some of the
      presentations, discussions and conclusions from Day 4 of the 'WHO EURO 2014
      International Healthy Cities Conference: Health and the City - Urban Living in
      the 21st Century', held in Athens, Greece on 25 October 2014. The Internet of
      Things (IoT) is made of sensors and other components that connect our version of
      the world made of atoms, i.e., humans/our bodies, our devices, vehicles, roads,
      buildings, plants, animals, etc., with a mirror digital version made of bits.
      This enables cities and regions to be self-aware and dynamically reconfigurable
      in real- or near-real-time, based on changes that are continuously monitored and
      captured by sensors, similar to the way the internal biological systems of a
      living being operate and respond to their environment (homeostasis). Data
      collected by various IoT sensors and processed via appropriate analytics can also
      help predict the immediate future with reasonable accuracy, which enables better
      planned responses and mitigation actions. Cities and regions can thus become more
      adaptable and resilient in face of adversity. Furthermore, IoT can link atoms
      (humans) to other atoms (humans) (again via bits), resulting in the formation of
      'smart(er) communities' that are socially connected in new ways and potentially
      happier. Cities, but also less urbanised regions and the countryside, could all
      benefit from, and harness the power of, IoT to improve the health, well-being and
      overall quality of life of the local populations, actively engage citizens in a
      smarter governance of their region, empower them to better care for one another,
      promote stronger social inclusion, and ensure a greener, sustainable and more
      enjoyable environment for all. Technology can also help reverse the 'brain drain'
      from the countryside and smaller towns to larger metropolises by making the
      former more attractive and connected, with better services akin to those found in
      larger cities. The article also discusses some ways of measuring and benchmarking
      the performance of smart cities and their impact on well-being. However, it
      should be emphasised that technology is not a panacea and that other factors are
      equally important in creating happier and healthier cities and regions. 

PMID- 25588544
TI  - Paradoxical his-atrial shortening: explain the mechanism.

PMID- 25588542
TI  - Anaplastic thyroid cancer: outcome and the mutation/expression profiles of
      potential targets.
AB  - Anaplastic thyroid cancer (ATC) is a rare but aggressive malignancy of the
      thyroid. No effective treatment modalities are currently available. Targeted
      therapy against protein kinases showed promising results in preclinical studies.
      Our goal was to assess the mutational status of potential therapeutic targets, as
      well as the biomarker for immunotherapy in the clinical context. Using allele
      specific PCR, Sanger sequencing, fragment analysis and immunohistochemistry, we
      assessed BRAF, KRAS, EGFR mutations and protein overexpression of C-KIT and PDL1
      in anaplastic thyroid cancer specimens. Results were compared to clinical
      information and patient outcome to assess the utility of these biomarkers. There
      were 13 patients in our study with a median overall survival of 19 weeks. Of the
      13 ATC patients, 3 (23 %) had BRAF V600E mutation. C-KIT overexpression was found
      in 1 (8 %) patient who responded well to a tyrosine kinase inhibitor. PDL1
      expression was seen in 3 (23 %) patients, none of them were surgical candidates
      due to unresectability and poor performance status. KRAS codon 12/13 and EGFR
      exon 18, 19, 20 and 21 were all wild type in our patients. Protein kinase
      inhibitors and immunotherapy may be useful adjuvant therapies for ATC.

PMID- 25588545
TI  - Menopause--natural selection or modern disease?

PMID- 25588546
TI  - Health knowledge, attitude, practice: the missing circle of breast cancer
      screening programs in Iran.

PMID- 25588547
TI  - Benzene partial hydrogenation: advances and perspectives.
AB  - The partial hydrogenation of benzene to cyclohexene is an economically
      interesting and technically challenging reaction. Over the last four decades, a
      lot of work has been dedicated to the development of an exploitable process and
      several approaches have been investigated. However, environmental constraints
      often represent a limit to their industrial application, making further research
      in this field necessary. The goal of this review is to highlight the main
      findings of the different disciplines involved in understanding the governing
      principles of this reaction from a sustainable chemistry standpoint. Special
      emphasis is given to ruthenium-catalyzed liquid phase batch hydrogenation of
      benzene. 

PMID- 25588548
TI  - Functional implications of the peptidoglycan recognition proteins in the immunity
      of the yellow fever mosquito, Aedes aegypti.
AB  - Peptidoglycan recognition proteins (PGRPs) play essential roles in the immune
      systems of insects and higher animals against certain pathogens, including
      bacteria. In insects, most studies on the functions of PGRPs have been performed
      in Drosophila, with only limited studies in mosquitoes, which are important
      disease vectors. In the present study, we analysed the PGRP sequences of the
      yellow fever mosquito, Aedes aegypti, acquired from two genome databases, and
      identified a total of seven PGRP genes; namely, PGRP-S1, -SC2, -LA, -LB, -LC, -LD
      and -LE. Bacterial injection using the Gram-negative bacteria Escherichia coli
      and the Gram-positive bacteria Micrococcus luteus showed that three PGRPs
      responded directly to both bacterial stimuli. Subsequently, the transcriptional
      expression of six of these PGRPs was knocked down using double-stranded RNA
      injection-based RNA interference (RNAi). RNAi of the PGRPs resulted in different
      impacts on the immune responses of Ae. aegypti to the two bacteria, as evidenced
      by the changes in mosquito survival rates after bacterial challenges as well as
      the differential regulation of several antimicrobial peptides and a number of
      other genes involved in mosquito immune pathways. Our data suggest that PGRP-LC
      is a significant factor in mediating immune responses to both E. coli and M.
      luteus, and the other PGRPs play only minor roles against these two bacteria,
      with PGRP-SC2 and -LB also serving as potential negative regulators for certain
      immune pathway(s) in Ae. aegypti. 

PMID- 25588549
TI  - Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp(3)
      C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems.
AB  - An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp(3) C-H
      activation and the direct arylation of the C3-position of oxygen heterocycles,
      such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient
      stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives
      (analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives
      (analogues of neolignans) is described. The direct C(sp(3))-H arylation of the C3
      position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the
      corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds
      with very high regio- and diastereoselectivities. The stereochemistry of the
      products obtained in this work were unambiguously assigned on the basis of the X
      ray structure analyses of representative compounds 3b, 3e, 4p, and 7. 

PMID- 25588550
TI  - Nanofabrication on unconventional substrates using transferred hard masks.
AB  - A major challenge in nanofabrication is to pattern unconventional substrates that
      cannot be processed for a variety of reasons, such as incompatibility with spin
      coating, electron beam lithography, optical lithography, or wet chemical steps.
      Here, we present a versatile nanofabrication method based on re-usable silicon
      membrane hard masks, patterned using standard lithography and mature silicon
      processing technology. These masks, transferred precisely onto targeted regions,
      can be in the millimetre scale. They allow for fabrication on a wide range of
      substrates, including rough, soft, and non-conductive materials, enabling feature
      linewidths down to 10 nm. Plasma etching, lift-off, and ion implantation are
      realized without the need for scanning electron/ion beam processing, UV exposure,
      or wet etching on target substrates.

PMID- 25588551
TI  - Expression and clinical significance of c-Met in advanced esophageal squamous
      cell carcinoma.
AB  - BACKGROUND: c-Met, one of current potential hot targets, has been suggested as a
      potential tumor marker in the development of esophageal squamous cell carcinoma
      (ESCC). Our aim was to investigate the expression of c-Met in advanced esophageal
      squamous cell carcinoma in four phase II trials who had tumor tissues from
      archival in our center and analyze the correlations between c-Met expression and
      clinical features. METHODS: Ninety patients with advanced ESCC who were admitted
      to the phase II clinical trials in the Department of Gastrointestinal Oncology,
      Peking University Cancer Hospital and Institute from March 2007 to March 2014
      were finally eligible for present study and the corresponding tissues and
      clinical data were collected. The expression of c-Met in the tissue samples was
      detected by immunohistochemistry (IHC). c-Met overexpression was defined as >=
      the median value of H-score. Kaplan-Meier and Cox multivariate regression were
      conducted to evaluate the relationship between c-Met expression and ESCC
      survival. RESULTS: The overexpression of c-Met is 43.3% in advanced ESCC. There
      was no statistical difference between c-Met expression and clinical features
      except sex and tumor location. Survival analysis documented that the
      overexpression of c-Met predicted a worse prognosis (OS: 253 d vs 422 d, P =
      0.011). In the group treated with chemotherapy combined with anti-EGFR drugs,
      patients with lowexpression of c-Met had a better OS than those with
      overexpression of c-Met (OS: 577 d vs 232 d, P = 0.007). CONCLUSIONS: c-Met may
      be an independent prognostic factor in advanced ESCC. The overexpression of c-Met
      may predict a worse efficacy of anti-EGFR therapy.

PMID- 25588552
TI  - Microbial quality of industrial liquid egg white: assumptions on spoiling issues
      in egg-based chilled desserts.
AB  - As a 1st step, this study aimed at investigating the microbial quality of liquid
      egg white in a French egg processing company. Thirty raw and 33 pasteurized
      liquid egg white samples were analyzed. Pasteurization was globally found
      efficient on mesophilic contaminants (1.7 +/- 1.6 and 0.8 +/- 0.9 log CFU/mL in
      raw and pasteurized samples, respectively), including for the control of
      Salmonella. However, Gram-positive enterococci were still detected in the
      pasteurized samples. As a 2nd step, a representative bacterial collection was
      built for exploring the spoilage issue in egg-based chilled desserts. Custard
      cream was chosen as growth medium since this food is widely used for the
      production of French chilled desserts. All of the 166 isolates of the bacterial
      collection were shown to be able to grow and to induce spoilage of the custard
      cream at refrigeration temperature (10  degrees C). Several spoilage types were
      highlighted in the custard cream, on the basis of changes regarding pH,
      consistency, production of holes or gas. As a 3rd step, bacterial enzymatic
      activities were explored on custard cream-based agar media. The bacterial
      collection was reduced to 43 isolates, based on further selection regarding the
      genera and the spoilage types previously highlighted. Albeit to different
      degrees, all these isolates were able to produce proteases. A large part of these
      isolates also expressed lipolytic and amylolytic activities. This study
      emphasizes the need to control egg white contamination and especially with Gram
      positive heat-resistant Enterococi, in order to guarantee the shelf life of egg
      based chilled desserts. 

PMID- 25588554
TI  - Systems approaches to unravel innate immune cell diversity, environmental
      plasticity and functional specialization.
AB  - Innate immune cells are generated through central and peripheral differentiation
      pathways, and receive multiple signals from tissue microenvironment. The complex
      interplay between immune cell state and environmental signals is crucial for the
      adaptation and efficient response to pathogenic threats. Here, we discuss how
      systems biology approaches have brought global view and high resolution to the
      characterization of (1) immune cell diversity, (2) phenotypic, transcriptional
      and functional changes in response to environmental signals, (3) integration of
      multiple stimuli. We will mostly focus on systems level studies in dendritic
      cells and macrophages. Generalization of these approaches should elucidate innate
      immune cell diversity and plasticity, and may be used in the human to generate
      hypothesis on cell filiation and novel strategies for immunotherapy. 

PMID- 25588553
TI  - Carotid plaque inflammation assessed with (18)F-FDG PET/CT is higher in
      symptomatic compared with asymptomatic patients.
AB  - BACKGROUND: Carotid artery plaque inflammation is thought to be an important
      marker of plaque vulnerability and increased stroke risk. AIM: The main aim of
      this study was to assess the level of agreement between 2-deoxy-2-[(18)F] fluoro
      D-glucose (18F-FDG) uptake on PET (positron emission tomography) scan in carotid
      plaques, with cerebrovascular symptoms, carotid plaque ultrasound echogenicity
      and histological assessments of plaque inflammation. METHODS: Thirty-six patients
      with >=70% carotid stenosis scheduled for carotid endarterectomy underwent a
      Colour Duplex ultrasound, (18)F-FDG PET/CT and blood tests less than 24 h prior
      to surgery. Plaques were defined as symptomatic when associated with ipsilateral
      cerebral ischemic symptoms within 30 days prior to inclusion. Plaques were
      assessed histologically following endarterectomy. The level of agreement between
      (18)F-FDG uptake (mean SUVmax and SUVmax ), and target-to-background ratio,
      symptoms, plaque echolucency, and histological evidence of inflammation was
      assessed. RESULTS: The amount of (18)F-FDG uptake in plaques and the amount of
      inflammation on histological assessment were significantly correlated (r = 0.521,
      P = 0.003). (18)F-FDG uptake was significantly higher in symptomatic plaques with
      median SUVmax 1.75 (1.26-2.04) in symptomatic, and 1.43 (1.15-2.28) in
      asymptomatic patients (P = 0.03). (18)F-FDG uptake was also positively correlated
      with echolucency on Doppler ultrasound (P = 0.03). CONCLUSION: (18)F-FDG uptake
      on PET/CT correlated with histological assessments of inflammation and was higher
      in patients with symptomatic compared with asymptomatic carotid artery plaques.
      These results support the use of (18)F-FDG PET/CT in the detection inflammation
      in carotid atherosclerosis, which may be of help in the detection of vulnerable
      plaques.

PMID- 25588555
TI  - Improved 1,3-Propanediol Synthesis from Glycerol by the Robust Lactobacillus
      reuteri Strain DSM 20016.
AB  - Various Lactobacillus reuteri strains were screened for the ability to convert
      glycerol to 1,3- propanediol (1,3-PDO) in a glycerol-glucose co-fermentation.
      Only L. reuteri DSM 20016, a well-known probiotic, was able to efficiently carry
      out this bioconversion. Several process strategies were employed to improve this
      process. CO(2+) addition to the fermentation medium, led to a high product titer
      (46 g/l) of 1,3-PDO and to improved biomass synthesis. L. reuteri DSM 20016
      produced also ca. 3 MUg/g of cell dry weight of vitamin B12, conferring an
      economic value to the biomass produced in the process. Incidentally, we found
      that L. reuteri displays the highest resistance to CO(2+) ions ever reported for
      a microorganism. Two waste materials (crude glycerol from biodiesel industry and
      spruce hydrolysate from paper industry) alone or in combination were used as
      feedstocks for the production of 1,3-PDO by L. reuteri DSM 20016. Crude glycerol
      was efficiently converted into 1,3-PDO although with a lower titer than pure
      glycerol (-18%). Compared with the fermentation carried out with pure substrates,
      the 1,3- PDO produced was significantly lower (40.7 vs. 24.2 g/l) using
      cellulosic hydrolysate and crude glycerol, but strong increases of the maximal
      biomass produced (+27%) and of the glucose consumption rate (+46%) were found.
      The results of this study lay the foundation for further investigations to
      exploit the biotechnological potential of L. reuteri DSM 20016 to produce 1,3-PDO
      and vitamin B12 using industry byproducts. 

PMID- 25588556
TI  - Gene Cloning, High-Level Expression, and Characterization of an Alkaline and
      Thermostable Lipase from Trichosporon coremiiforme V3.
AB  - The present study describes the gene cloning and high-level expression of an
      alkaline and thermostable lipase gene from Trichosporon coremiiforme V3.
      Nucleotide analysis revealed that this lipase gene has an open reading frame of
      1,692 bp without any introns, encoding a protein of 563 amino acid residues. The
      lipase gene without its signal sequence was cloned into plasmid pPICZalphaA and
      overexpressed in Pichia pastoris X33. The maximum lipase activity of recombinant
      lipase was 5,000 U/ml, which was obtained in fed-batch cultivation after 168 h
      induction with methanol in a 50 L bioreactor. The purified lipase showed high
      temperature tolerance, and being stable at 60  degrees C and kept 45% enzyme
      activity after 1 h incubation at 70  degrees C. The stability, effects of metal
      ions and other reagents were also determined. The chain length specificity of the
      recombinant lipase showed high activity toward triolein (C18:1) and tripalmitin
      (C16:0).

PMID- 25588557
TI  - Kinetic and Energetic Parameters of Carob Wastes Fermentation by Saccharomyces
      cerevisiae: Crabtree Effect, Ethanol Toxicity, and Invertase Repression.
AB  - Carob waste is a useful raw material for the second-generation ethanol because
      50% of its dry weight is sucrose, glucose, and fructose. To optimize the process,
      we have studied the influence of the initial concentration of sugars on the
      fermentation performance of Saccharomyces cerevisiae. With initial sugar
      concentrations (S0) of 20 g/l, the yeasts were derepressed and the ethanol
      produced during the exponential phase was consumed in a diauxic phase. The rate
      of ethanol consumption decreased with increasing S0 and disappeared at 250 g/l
      when the Crabtree effect was complete and almost all the sugar consumed was
      transformed into ethanol with a yield factor of 0.42 g/g. Sucrose hydrolysis was
      delayed at high S0 because of glucose repression of invertase synthesis, which
      was triggered at concentrations above 40 g/l. At S0 higher than 250 g/l, even
      when glucose had been exhausted, sucrose was hydrolyzed very slowly, probably due
      to an inhibition at this low water activity. Although with lower metabolic rates
      and longer times of fermentation, 250 g/l is considered the optimal initial
      concentration because it avoids the diauxic consumption of ethanol and maintains
      enough invertase activity to consume all the sucrose, and also avoids the
      inhibitions due to lower water activities at higher S0. 

PMID- 25588558
TI  - Expression of Auxin Response Genes SlIAA1 and SlIAA9 in Solanum lycopersicum
      During Interaction with Acinetobacter guillouiae SW5.
AB  - Indole-3-acetic acid (IAA) production is a typical mechanism of plant growth
      promotion by some rhizobacteria. However, a functional genomic study is necessary
      to unravel the function and mechanism of IAA signaling during rhizobacteria-plant
      interactions. In this study, the expression of SlIAA1 and SlIAA9 among the auxin
      response genes in tomato was examined during the interaction between IAA
      producing Acinetobacter guillouiae SW5 and tomato plants. When 3-day grown tomato
      seedlings were treated for 30 min with 10~100 uM of IAA produced by bacteria from
      tryptophan, the relative mRNA levels of SlIAA1 and SlIAA9 increased significantly
      compared with those of the control, demonstrating that IAA produced by this
      bacterium can induce the expressions of both genes. Inoculation of live A.
      guillouiae SW5 to tomato seedlings also increased the expressions of SlIAA1 and
      SlIAA9, with more mRNA produced at higher bacterial density. In contrast,
      treatment of tomato seedlings with dead A. guillouiae SW5 did not significantly
      affect the expression of SlIAA1and SlIAA9. When 3-day bacterial culture in tomato
      root exudates was administered to tomato seedlings, the relative mRNA level of
      SlIAA1 increased. This result indicated that the plant may take up IAA produced
      by bacteria in plant root exudates, which may increase the expression of the
      auxin response genes, with resulting promotion of plant growth. 

PMID- 25588559
TI  - Cloning, Expression, and Purification of Recombinant Uricase Enzyme from
      Pseudomonas aeruginosa Ps43 Using Escherichia coli.
AB  - Uricase is an important microbial enzyme that can be used in the clinical
      treatment of gout, hyperuricemia, and tumor lysis syndrome. A total of 127
      clinical isolates of Pseudomonas aeruginosa were tested for uricase production. A
      Pseudomonas strain named Ps43 showed the highest level of native uricase enzyme
      expression. The open reading frame of the uricase enzyme was amplified from Ps43
      and cloned into the expression vector pRSET-B. Uricase was expressed using E.
      coli BL21 (DE3). The ORF was sequenced and assigned GenBank Accession No.
      KJ718888. The nucleotide sequence analysis was identical to the coding sequence
      of uricase gene puuD of P. aeruginosa PAO1. We report the successful expression
      of P. aeruginosa uricase in Escherichia coli. E. coli showed an induced protein
      with a molecular mass of about 58 kDa that was confirmed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and Western blotting. We also
      established efficient protein purification using the Ni-Sepharose column with
      activity of the purified enzyme of 2.16 IU and a 2-fold increase in the specific
      activity of the pure enzyme compared with the crude enzyme. 

PMID- 25588560
TI  - Cloning, Overexpression, and Characterization of a Metagenome-Derived Phytase
      with Optimal Activity at Low pH.
AB  - A phytase gene was identified in a publicly available metagenome derived from
      subsurface groundwater, which was deduced to encode for a protein of the
      histidine acid phosphatase (HAP) family. The nucleotide sequence of the phytase
      gene was chemically synthesized and cloned, in order to further overexpress the
      phytase in Escherichia coli. Purified protein of the recombinant phytase
      demonstrated an activity for phytic acid of 298 +/- 17 MUmol P/min/mg, at the pH
      optimum of 2.0 with the temperature of 37  degrees C. Interestingly, the pH
      optimum of this phytase is much lower in comparison with most HAP phytases known
      to date. It suggests that the phytase could possess improved adaptability to the
      low pH condition caused by the gastric acid in livestock and poultry stomachs.

PMID- 25588561
TI  - Validation of Heterodimeric TAT-NLS Peptide as a Gene Delivery Enhancer.
AB  - Cationic liposomes have been actively used as gene delivery vehicles despite
      their unsatisfactory efficiencies because of their relatively low toxicity. In
      this study, we designed novel heterodimeric peptides as nonviral gene delivery
      systems from TAT and NLS peptides using cysteine-to-cysteine disulfide bonds
      between the two. Mixing these heterodimeric peptides with DNA before mixing with
      lipofectamine resulted in higher transfection efficiencies in MCF-7 breast cancer
      cells than mixing unmodified TAT, NLS, and a simple mixture of TAT and NLS with
      DNA, but did not show an adverse effect on cell viability. In gel retardation
      assays, the DNA binding affinities of heterodimeric peptides were stronger than
      NLS but weaker than TAT. However, this enhancement was only observed when
      heterodimeric peptides were premixed with DNA before being mixed with
      lipofectamine. The described novel transfection-enhancing peptide system produced
      by the heterodimerization of TAT and NLS peptides followed by simple mixing with
      DNA, increased the gene transfer efficiency of cationic lipids without enhancing
      cytotoxicity. 

PMID- 25588562
TI  - RETRACTION: The response differences of rubisco and cpcE-F genes to H2O2 in four
      Spirulina platensis strains.

PMID- 25588563
TI  - Active learning strategies to teach undergraduate nursing statistics: connecting
      class and clinical to prepare students for evidence-based practice.

PMID- 25588564
TI  - PCR-based specific techniques used for detecting the most important pathogens on
      strawberry: a systematic review.
AB  - BACKGROUND: Strawberry diseases are a major limiting factor that severely impact
      plant agronomic performance. Regarding limitations of traditional techniques for
      detection of pathogens, researchers have developed specific DNA-based tests as
      sensitive and specific techniques. The aim of this review is to provide an
      overview of polymerase chain reaction (PCR)-based methods used for detection or
      quantification of the most widespread strawberry pathogens, such as Fusarium
      oxysporum f.sp. fragariae, Phytophthora fragariae, Colletotrichum acutatum,
      Verticillium dahliae, Botrytis cinerea, Macrophomina phaseolina, and Xanthomonas
      fragariae. An updated and detailed list of published PCR protocols is presented
      and discussed, aimed at facilitating access to information that could be
      particularly useful for diagnostic laboratories in order to develop a rapid, cost
      effective, and reliable monitoring technique. METHODS: The study design was a
      systematic review of PCR-based techniques used for detection and quantification
      of strawberry pathogens. Using appropriate subject headings, AGRICOLA, AGRIS,
      BASE, Biological Abstracts, CAB Abstracts, Google Scholar, Scopus, Web of
      Knowledge, and SpringerLink databases were searched from their inception up to
      April 2014. Two assessors independently reviewed the titles, abstracts, and full
      articles of all identified citations. Selected articles were included if one of
      the mentioned strawberry pathogens was investigated based on PCR methods, and a
      summary of pre-analytical requirements for PCR was provided. RESULTS: A total of
      259 titles and abstracts were reviewed, of which 22 full texts met all the
      inclusion criteria. Our systematic review identified ten different protocols for
      X. fragariae, eight for P. fragariae, four for B. cinerea, six for C. acutatum,
      three for V. dahlia, and only one for F. oxysporum. The accuracy and sensitivity
      of PCR diagnostic methods is the focus of most studies included in this review.
      However, a large proportion of errors in laboratories occur in the pre-analytical
      phase of the testing process. Due to heterogeneity, results could not be meta
      analyzed. CONCLUSIONS: From a systematic review of the currently available
      published literature, effective detection assays to detect the major strawberry
      pathogens have been developed. These assays can function as a basis for clinical
      labs, regulatory personnel, and other diagnosticians to adapt or implement for
      detection of these six important strawberry pathogens.

PMID- 25588565
TI  - Deterministic entanglement distillation for secure double-server blind quantum
      computation.
AB  - Blind quantum computation (BQC) provides an efficient method for the client who
      does not have enough sophisticated technology and knowledge to perform universal
      quantum computation. The single-server BQC protocol requires the client to have
      some minimum quantum ability, while the double-server BQC protocol makes the
      client's device completely classical, resorting to the pure and clean Bell state
      shared by two servers. Here, we provide a deterministic entanglement distillation
      protocol in a practical noisy environment for the double-server BQC protocol.
      This protocol can get the pure maximally entangled Bell state. The success
      probability can reach 100% in principle. The distilled maximally entangled states
      can be remaind to perform the BQC protocol subsequently. The parties who perform
      the distillation protocol do not need to exchange the classical information and
      they learn nothing from the client. It makes this protocol unconditionally secure
      and suitable for the future BQC protocol.

PMID- 25588566
TI  - Is modern external beam radiotherapy with androgen deprivation therapy still a
      viable alternative for prostate cancer in an era of robotic surgery and
      brachytherapy: a comparison of Australian series.
AB  - INTRODUCTION: We compare the results of modern external-beam radiotherapy (EBRT),
      using combined androgen deprivation and dose-escalated intensity-modulated
      radiotherapy with MRI-CT fusion and daily image guidance with fiducial markers
      (DE-IG-IMRT), with recently published Australian series of brachytherapy and
      surgery. METHODS: Five-year actuarial biochemical disease-free survival (bDFS),
      metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS) were
      calculated for 675 patients treated with DE-IG-IMRT and androgen deprivation
      therapy (ADT). Patients had intermediate-risk (IR) and high-risk (HR) disease. A
      search was conducted identifying Australian reports from 2005 onwards of IR and
      HR patients treated with surgery or brachytherapy, reporting actuarial outcomes
      at 3 years or later. RESULTS: With a median follow-up of 59 months, our 5-year
      bDFS was 93.3% overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9%
      overall (99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR).
      Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years was
      1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade 3
      gastrointestinal toxicity. Eight reports of brachytherapy and surgery were
      identified. The HDR brachytherapy series' median 5-year bDFS was 82.5%, MFS 90.0%
      and PCaSS 97.9%. One surgical series reported 5-year bDFS of 65.5% for HR
      patients. One LDR series reported 5-year bDFS of 85% for IR patients.
      CONCLUSIONS: Modern EBRT is at least as effective as modern Australian surgical
      and brachytherapy techniques. All patients considering treatment for localised
      prostate cancer should be referred to a radiation oncologist to discuss EBRT as
      an equivalent option.

PMID- 25588567
TI  - Role of indigenous arsenate and iron(III) respiring microorganisms in controlling
      the mobilization of arsenic in a contaminated soil sample.
AB  - In this study two different treatment options were investigated for the release
      of arsenic from a contaminated soil sample. The first option was based on the
      "bioaugmentation" principle and involved addition of a pure Fe(III)-reducing
      culture, i.e. Desulfuromonas palmitatis. The second option consisted in the
      "biostimulation" of indigenous bacteria and involved simple addition of
      nutrients. Due to the strong association of As with soil ferric oxides, the
      reductive dissolution of soil oxides by D. palmitatis lead to 45 % arsenic
      release in solution (2.15 mM). When only nutrients were supplied to the soil, the
      same amounts of Fe and As were dissolved with slower rates and most aqueous As
      was found to be in the trivalent state, indicating the presence of arsenate
      reducing species. The arsenate reducing microorganisms were enriched with
      successive cultures, using Na2HAsO4 as electron acceptor. The phylogenetic
      analysis revealed that the enriched microbial consortium contained
      Desulfosporosinus species, which are known arsenate reducers.

PMID- 25588568
TI  - Preoperative intra-aortic balloon pump to reduce mortality in coronary artery
      bypass graft: a meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: The intra-aortic balloon pump is routinely used in cardiac surgery;
      however, its impact on outcome is still a matter of debate and several randomized
      trials have been published recently. We perform an updated meta-analysis of
      randomized controlled trials that investigated the use of preoperative intra
      aortic balloon pump in adult patients undergoing coronary artery bypass grafting.
      METHODS: Potentially eligible trials were identified by searching the Medline,
      Embase, Scopus, ISI Web of Knowledge and The Cochrane Library. Searches were not
      restricted by language or publication status and were updated in August 2014.
      Randomized controlled trials on preoperative intra-aortic balloon pump in
      patients undergoing coronary artery bypass grafting either with or without
      cardiopulmonary bypass were identified. The primary end point was mortality at
      the longest follow-up available and the secondary end point was 30-day mortality.
      RESULTS: The eight included randomized clinical trials enrolled 625 patients (312
      to the intra-aortic balloon pump group and 313 to control). The use of intra
      aortic balloon pump was associated with a significant reduction in the risk of
      mortality (11 of 312 (3.5%) versus 33 of 313 (11%), risk ratio = 0.38 (0.20 to
      0.73), P for effect = 0.004, P for heterogeneity = 0.7, I-square = 0%, with eight
      studies included). The benefit on mortality reduction was confirmed restricting
      the analysis to trials with low risk of bias, to those reporting 30-day follow-up
      and to patients undergoing coronary artery bypass graft surgery with
      cardiopulmonary bypass. CONCLUSIONS: Preoperative intra-aortic balloon pump
      reduces perioperative and 30-day mortality in high-risk patients undergoing
      elective coronary artery bypass grafting.

PMID- 25588569
TI  - Characterization of a novel clade of Xanthomonas isolated from rice leaves in
      Mali and proposal of Xanthomonas maliensis sp. nov.
AB  - Four bacterial strains, designated M89, M92, M97(T), and M106, were isolated in a
      previous study from surface-sterilized leaves of rice (Oryza sativa) or
      murainagrass (Ischaemum rugosum) at three sites in Mali, Africa. Here they were
      examined by a polyphasic taxonomic approach and analysis of a whole-genome
      sequence. Phylogenetic analyses based on 16S rRNA sequence and multilocus
      sequence analysis of seven genes showed that these four strains formed a distinct
      lineage representing a novel species within the genus Xanthomonas. This was
      supported by whole-genome average nucleotide identity values calculated from
      comparisons of strain M97(T) with established Xanthomonas species. The strains
      can be differentiated from the known Xanthomonas species on the basis of their
      fatty acid and carbohydrate utilization profiles. Population growth studies on
      rice confirmed that these bacteria multiply in rice leaves without causing
      symptoms. Identification of this novel species can be accomplished by using
      diagnostic primer sets or by gyrB gene sequence analysis. We propose to classify
      these rice- and grass-associated bacteria as Xanthomonas maliensis sp. nov. with
      strain M97(T) = CFBP7942(T) = LMG27592(T) as the type strain. 

PMID- 25588571
TI  - Burden of blood transmitted infections in substance users admitted for inpatient
      treatment in Singapore and the associated factors.
AB  - INTRODUCTION: There is paucity of local data on the prevalence of blood
      transmitted infections (BTIs), such as hepatitis B, hepatitis C and human
      immunodeficiency virus (HIV) infections, among illicit drug users. This study
      aimed to examine the prevalence of BTIs among substance dependent inpatients and
      identify the factors associated with BTIs. METHODS: We conducted a retrospective
      analysis of clinical notes of 170 inpatients with a diagnosis of substance
      dependence who were admitted at the National Addictions Management Service,
      Singapore, between 1 June 2009 and 31 May 2010. RESULTS: Majority of the 170
      inpatients were male (88.2%) and Chinese (58.2%). The mean age of the patients
      was 43.1 years, and the main drug of abuse was opioids (86.5%). BTIs were found
      in 70 (41.2%) inpatients; the prevalence of hepatitis B, hepatitis C and HIV
      infections was 3.7%, 39.6% and 0%, respectively. Lifetime intravenous drug use,
      but not needle-sharing, was more common among inpatients who were positive for
      BTIs (p < 0.01). Logistic regression analysis showed that lifetime intravenous
      drug use (OR 4.3, 95% CI 1.7- 10.8, p < 0.01) was the only significant predictor
      of BTIs. CONCLUSION: A large proportion (41.2%) of the substance users seeking
      help was positive for at least one BTI. Lifetime intravenous drug users were
      found to be more than four times more likely to have a BTI. Early detection and
      prevention is essential to improve prognosis.

PMID- 25588572
TI  - Development of a peptidomimetic antagonist of neuropeptide FF receptors for the
      prevention of opioid-induced hyperalgesia.
AB  - Through the development of a new class of unnatural ornithine derivatives as
      bioisosteres of arginine, we have designed an orally active peptidomimetic
      antagonist of neuropeptide FF receptors (NPFFR). Systemic low-dose administration
      of this compound to rats blocked opioid-induced hyperalgesia, without any
      apparent side-effects. Interestingly, we also observed that this compound
      potentiated opioid-induced analgesia. This unnatural ornithine derivative
      provides a novel therapeutic approach for both improving analgesia and reducing
      hyperalgesia induced by opioids in patients being treated for chronic pain. 

PMID- 25588573
TI  - Evaluation of right ventricular function using single-beat three-dimensional
      echocardiography in neonate.
AB  - Aim of our study was to evaluate right ventricular (RV) systolic function in
      neonate using newly developed single-beat three-dimensional echocardiography
      (sb3DE). We enrolled 15 healthy or premature neonates (0-53 days after birth). We
      scanned one beat full volume using Siemens ACUSON SC2000 (Siemens AG)
      echocardiography with 4Z1c full-volume transducer without ECG gating. RV end
      diastolic volume (RVEDV) and RV end-systolic volume (RVESV) were computed with
      special software dedicated to analysis for RV volume. RV ejection fraction (RVEF)
      and RV stroke volume (3D-RVSV) were calculated. And RV stroke volume was also
      determined from the recordings of ejection blood flow velocity and diameter at
      the level of the pulmonary orifice in RV outflow tract (Doppler-RVSV). Tricuspid
      annular plane systolic excursion (TAPSE) was also measured by 2D
      echocardiography. RVEDV ranged from 5.1 to 10.7 ml (average 7.5 ml), RVESV ranged
      from 2.3 to 5.8 ml (average 3.9 ml). There was a good correlation between 3D-RVSV
      and Doppler-RVSV (r = 0.77). Bland-Altman plot revealed that 3D-RVSV became
      underestimation of an average of 1.78 ml compared to Doppler-RVSV. And TAPSE
      positively correlated with 3D-RVEF (r = 0.58, P = 0.038). Newly developed sb3DE
      enables us to perform three-dimensional acquisition of RV volume without ECG
      gating even in neonate. However, 3D-RVSV currently tends to be underestimated in
      neonatal measurement.

PMID- 25588574
TI  - Brazilian Group of Flow Cytometry (GBCFLUX) panels for acute leukemias--Response
      to Matos.

PMID- 25588575
TI  - Aiding a reassertion of self: a qualitative study of the views and experiences of
      women with ovarian cancer receiving long-term nurse-led telephone follow-up.
AB  - PURPOSE: This study explored the views and experiences of women following
      treatment for ovarian cancer who had received long-term (at least 3 years) nurse
      led telephone follow-up. Exploring the long-term experiences of follow-up for
      women with ovarian cancer provides important information regarding the coping
      processes of cancer survivors that can inform the development of innovative and
      patient-centred approaches of cancer follow-up. METHODS: This is a qualitative
      study approach using interpretative phenomenological analysis (IPA). Eleven women
      were identified by a clinical nurse specialist as having received nurse-led
      telephone follow-up for a period of at least 3 years. These women were
      interviewed in person or over the telephone using a semi-structured interview
      schedule; interviews were audio-recorded and transcriptions were analysed using
      IPA. RESULTS: Nurse-led telephone follow-up was felt to support a reassertion of
      self and a rejection of patient identity. Three core themes emerged regarding the
      positive impact of nurse-led telephone follow-up: 'Somebody was looking out for
      me' highlights the perception of increased psychosocial support; 'It's just
      reassurance' includes both the deep trust in the expertise of the nurse and the
      reassurance of the continued blood tests; and 'Time was never an issue' presents
      the perception of relaxed follow-up appointments with time to talk and the
      perceived practical benefits of this approach. CONCLUSIONS: Nurse-led telephone
      follow-up was broadly recommended for women following treatment for ovarian
      cancer, particularly for those later on in the survivorship trajectory when focus
      may move from biomedical aspects of cure to holistic approaches to well-being.
      Remote interventions which provide a perception of a consistent and constant
      source of medical and psychosocial support may support adaption to cancer
      survivorship by enabling a reassertion of self and a rejection of patient
      identity.

PMID- 25588577
TI  - Erratum to: heterosexual couples and prostate cancer support groups: a gender
      relations analysis.

PMID- 25588576
TI  - Communication dysfunction, body image, and symptom severity in postoperative head
      and neck cancer patients: factors associated with the amount of speaking after
      treatment.
AB  - PURPOSE: The purpose of this study was to determine the relationships of
      communication dysfunction, body image, and amount of speaking in patients who
      were treated for head and neck cancers (HNCs). METHODS: This was a cross
      sectional study of postoperative HNC patients at the otolaryngology outpatient
      departments of two leading medical centers in northern Taiwan. Data were
      collected using questionnaires to assess perceived communication dysfunction,
      body image, symptom severity, and amount of speaking after treatment. RESULTS: A
      total of 130 HNC patients were included in the analysis, and 70.8 % of patients
      reported speaking less after surgery as compared to the period before having HNC
      surgery. Overall, patients perceived a moderate level of communication
      dysfunction. Those with higher distress over their body image, higher symptom
      severity, and with hypopharyngeal and laryngeal cancer reported speaking less.
      Patients with advanced stage cancer and a tumor in a facial area and those that
      received reconstructive surgery were more likely to have a negative body image.
      CONCLUSIONS: Dissatisfaction with body image, greater symptom severity, and
      hypopharyngeal and laryngeal cancer are predictive of the amount HNC patients
      speak, as compared with the amount they spoke before having HNC. Clinicians
      should be aware of and systematically assess communication problems of HNC
      patients to promote their social function. Further research on interventions that
      facilitate the development of a positive body image and communication is strongly
      suggested.

PMID- 25588578
TI  - Coping with an altered mouth and perceived supportive care needs following head
      and neck cancer treatment.
AB  - PURPOSE: Oral health is essential to general health and well-being and is
      severely impacted by head and neck cancer (HNC) and its treatment. This study
      aimed to describe how people who have been treated for HNC cope with altered oral
      health and function and to identify their supportive care needs. METHODS: A
      qualitative, descriptive approach was used. Data was collected from individual
      interviews with six participants 6 months after treatment. Data analysis was
      performed by qualitative content analysis involving inductive and directed
      approaches. Directed content analysis was guided by the Stress, Appraisal and
      Coping Model. RESULTS: Three themes describing changed oral health were
      identified from the data: dimensions of eating, maintaining oral health after
      treatment and adapting to the chronic side effects of treatment. A strong use of
      problem-focussed coping was described, in addition to the importance of peer
      support in adapting to the psychosocial outcomes of treatment. Support needs
      identified related to increased access to specialist dental oncology services
      post treatment, information needs and a need for more psychological support.
      CONCLUSION: The study findings describe the experience of a sample of people who
      have received treatment for HNC. Due to a demographically homogenous sample and
      the strong use of positive coping strategies, the results presented may not
      describe the experience of the wider HNC population; however, these results
      provide insight into factors that may influence positive coping.

PMID- 25588579
TI  - The toxicity of acute exposure to T-2 toxin evaluated by the metabonomics
      technique.
AB  - T-2 toxin is a common contaminant in grains and animal feedstuff, which becomes
      an increasing threat to human and animal health due to its high toxicity.
      Investigating the systemic effects of T-2 toxin is important to evaluate the
      toxicity and facilitate the assessment of food safety. In our investigation, rats
      were treated with a single dose of T-2 toxin at dosage levels of 0, 0.5, 2.0 and
      4.0 mg kg(-1) body weight via gavage. The metabolic profiles of body fluids and
      multiple organs were obtained by NMR spectroscopy and analyzed by multivariate
      data analysis methods. The results showed that low and moderate doses of T-2
      toxin only influenced the urinary metabonomes, while a high dose of T-2 toxin
      induced metabolic alterations in urine and multiple organs. These changes
      included alterations in the levels of membrane metabolites, TCA cycle
      intermediates, a range of amino acids, nucleosides and nucleotides. T-2 toxin
      exposure impaired spleen function, causing immunotoxicity, and inhibited protein
      and DNA biosynthesis. In addition, T-2 toxin also caused oxidative stress and
      disturbance in energy metabolism and gut microbiome. Our work provided a
      comprehensive insight into T-2 toxicity and revealed the great potential of
      metabonomics in assessing the impact of a toxic compound. 

PMID- 25588580
TI  - Reversing synapse loss in Alzheimer's disease: Rho-guanosine triphosphatases and
      insights from other brain disorders.
AB  - Alzheimer's disease (AD) is a monumental public health crisis with no effective
      cure or treatment. To date, therapeutic strategies have focused almost
      exclusively on upstream signaling events in the disease, namely on beta-amyloid
      and amyloid precursor protein processing, and have, unfortunately, yielded few,
      if any, promising results. An alternative approach may be to target signaling
      events downstream of beta-amyloid and even tau. However, with so many pathways
      already linked to the disease, understanding which ones are "drivers" versus
      "passengers" in the pathogenesis of the disease remains a tremendous challenge.
      Given the critical roles of Rho-guanosine triphosphatases (GTPases) in regulating
      the actin cytoskeleton and spine dynamics, and the strong association between
      spine abnormalities and cognition, it is not surprising that mutations in a
      number of genes involved in Rho-GTPase signaling have been implicated in several
      brain disorders, including schizophrenia and autism. And now, there is mounting
      literature implicating Rho-GTPase signaling in AD pathogenesis as well. Here, I
      review this evidence, with a particular emphasis on the regulators of Rho-GTPase
      signaling, namely guanine nucleotide exchange factors and GTPase-activating
      proteins. Several of these have been linked to various aspects of AD, and each
      offers a novel potential therapeutic target for AD. 

PMID- 25588581
TI  - Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain
      by Different Routes: Therapeutic Implications.
AB  - Resveratrol possesses anti-tumor activities against central nervous system (CNS)
      tumors in vitro but has not yet been used clinically due to its low
      bioavailability, particularly in the CNS. This study thus aimed to elucidate
      brain bioavailability of trans-resveratrol by monitoring brain concentrations and
      dwell times following administration of resveratrol through intragastric,
      intraperitoneal, external carotid artery/ECA and intrathecal routes. In parallel,
      we evaluated the biological responses of rat RG2 glioblastoma cells as well as
      RG2-formed rat intracranial glioblastomas treated with resveratrol via
      intrathecal administration. The results revealed that resveratrol was detected in
      rat brains except when administered systemically. Intrathecal administration of
      reseveratrol led to abundant apoptotic foci and increased staining of the
      autophagy proteins, LC-3 and Beclin-1 and shrinkage of the intracranial tumors.
      In conclusion, the BBB penetrability of resveratrol is remarkably increased by
      intracthecal administration. Regular short-term resveratrol treatments suppress
      growth and enhance autophagic and apoptotic activities of rat RG2 glioblastoma
      cells in vitro and in vivo. Therefore, intrathecal administration of resveratrol
      could be an optimal intervention approach in the adjuvant management of brain
      malignancies. 

PMID- 25588582
TI  - Heterochromatin Protein 1 Alpha (HP1alpha: CBX5) is a Key Regulator in
      Differentiation of Endothelial Progenitor Cells to Endothelial Cells.
AB  - As the ability to control the differentiation of endothelial stem/progenitor
      cells (EPCs) into vascular endothelial cell lineages could be useful for
      promoting neovascularization, it is important to obtain a deeper understanding of
      the epigenetic mechanisms that regulate EPC differentiation and
      neovascularization. Heterochromatin protein 1alpha (HP1alpha) is known to be
      involved in the epigenetic regulation of gene silencing. However, recent reports
      demonstrate that HP1alpha can also activate gene expression during cell
      differentiation. In this study, microarray analysis revealed that HP1alpha
      expression was induced during EPC differentiation and is associated with the
      expression of outgrowing endothelial cell (OEC)-specific protein markers. To
      explore the role of HP1alpha in the differentiation of EPCs to OECs, its
      expression was knocked-down or over-expressed in differentiating EPCs.
      Overexpression of HP1alpha promoted the differentiation and angiogenic activity
      of EPCs in vitro and in vivo, whereas knockdown of HP1alpha led to a defect in
      OEC migration, tube formation, and angiogenic sprouting activity. Gene expression
      profiling showed increased expression of angiogenic genes, including NOTCH1,
      cadherin-5, and angiopoietin-like-2, and decreased expression of progenitor cell
      marker genes, including CD133, CXCR4, and C-KIT, in HP1alpha-overexpressing EPCs.
      Also, increased HP1alpha at an early stage of EPC differentiation may regulate
      angiogenic gene transcription by interacting with chromatin that modifies
      epigenetic factors such as the methyl-CpG binding domain, Polycomb group ring
      finger 2, and DNA methyltransferases. Our findings demonstrate, for the first
      time, that HP1alpha plays an important role in the differentiation and angiogenic
      function of EPCs by regulating endothelial gene expression. Stem Cells
      2015;33:1512-1522. 

PMID- 25588583
TI  - From exaggeration to silence in health related science news and academic press
      releases: mindful bias?

PMID- 25588585
TI  - Guidelines for skeletal survey in young children with fractures.

PMID- 25588584
TI  - Dignified Palliative Long-Term Care: An Interpretive Systemic Framework of End-of
      Life Integrated Care Pathway for Terminally Ill Chinese Older Adults.
AB  - PURPOSE: To critically examine the system dynamics necessary for successfully
      implementing a novel end-of-life integrated care pathway (EoL-ICP) program in
      promoting dignity and quality of life among terminally-ill Chinese nursing home
      residents. METHODS: Thirty stakeholders were recruited to participate in 4
      interpretive-systemic focus groups. RESULTS: Framework analysis revealed 10
      themes, organized into 3 categories, namely, (1) Regulatory Empowerment
      (interdisciplinary teamwork, resource allocation, culture building, collaborative
      policy making), (2) Family-Centered Care (continuity of care, family care
      conference, partnership in care), and (3) Collective Compassion (devotion in
      care, empathic understanding, compassionate actions). CONCLUSIONS: These findings
      highlight the importance of organizational structure, social discourse, and
      shared meaning in the provision of EoL-ICP in Chinese societies, underscoring the
      significant triangulation between political, cultural, and spiritual contexts
      embodied in the experience of dignity.

PMID- 25588586
TI  - Accuracy of ultrasound-guided intra-articular injections in guinea pig knees.
AB  - OBJECTIVE: Dunkin Hartley guinea pigs, a commonly used animal model of
      osteoarthritis, were used to determine if high frequency ultrasound can ensure
      intra-articular injections are accurately positioned in the knee joint. METHODS:
      A high-resolution small animal ultrasound system with a 40 MHz transducer was
      used for image-guided injections. A total of 36 guinea pigs were anaesthetised
      with isoflurane and placed on a heated stage. Sterile needles were inserted
      directly into the knee joint medially, while the transducer was placed on the
      lateral surface, allowing the femur, tibia and fat pad to be visualised in the
      images. B-mode cine loops were acquired during 100 ul. We assessed our ability to
      visualise 1) important anatomical landmarks, 2) the needle and 3) anatomical
      changes due to the injection. RESULTS: From the ultrasound images, we were able
      to visualise clearly the movement of anatomical landmarks in 75% of the
      injections. The majority of these showed separation of the fat pad (67.1%),
      suggesting the injections were correctly delivered in the joint space. We also
      observed dorsal joint expansion (23%) and patellar tendon movement (10%) in a
      smaller subset of injections. CONCLUSION: The results demonstrate that this image
      guided technique can be used to visualise the location of an intra-articular
      injection in the joints of guinea pigs. Future studies using an ultrasound-guided
      approach could help improve the injection accuracy in a variety of anatomical
      locations and animal models, in the hope of developing anti-arthritic therapies.
      Cite this article: Bone Joint Res 2015;4:1-5.

PMID- 25588587
TI  - Intravenous iron isomaltoside 1000 administered by high single-dose infusions or
      standard medical care for the treatment of fatigue in women after postpartum
      haemorrhage: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Postpartum haemorrhage can lead to iron deficiency with and without
      anaemia, the clinical consequences of which include physical fatigue. Although
      oral iron is the standard treatment, it is often associated with gastrointestinal
      side effects and poor compliance. To date, no published randomised controlled
      studies have compared the clinical efficacy and safety of standard medical care
      with intravenous administration of iron supplementation after postpartum
      haemorrhage.The primary objective of this study is to compare the efficacy of an
      intravenous high single-dose of iron isomaltoside 1000 with standard medical care
      on physical fatigue in women with postpartum haemorrhage. METHODS/DESIGN: In a
      single centre, open-labelled, randomised trial, women with postpartum haemorrhage
      exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron
      isomaltoside 1000 or standard medical care. Healthy parturients with a singleton
      pregnancy will be included within 48 hours after delivery.Participants will
      complete structured questionnaires that focus on several dimensions of fatigue
      and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal
      Depression Scale and the Postpartum Questionnaire), at inclusion and at follow-up
      visits after three days, one week, three weeks, eight weeks, and 12 weeks
      postpartum. The primary endpoint is the aggregated change in physical fatigue
      score within 12 weeks postpartum, as measured by a subscale of the
      Multidimensional Fatigue Inventory. The primary objective will be considered to
      have been met if an intravenous high single dose of iron isomaltoside 1000 is
      shown to be superior to standard medical care in women after postpartum
      haemorrhage regarding physical fatigue.For claiming superiority, we set the
      minimal clinically relevant difference between the mean scores at 1.8, and the
      assumed standard deviation at 4.2. Hence, 87 participants per treatment group are
      needed in order to demonstrate superiority; to provide an extra margin for
      missing data and dropouts, 200 women will be included. DISCUSSION: The study will
      provide evidence on relevant clinical outcomes beyond biochemical parameters for
      intravenous iron isomaltoside 1000 compared to standard medical care in women
      after postpartum haemorrhage. TRIAL REGISTRATION: This trial is registered with
      Clinicaltrials.gov (identifier: NCT01895218) on 26 June 2013.

PMID- 25588588
TI  - An in vitro bone tissue regeneration strategy combining chondrogenic and vascular
      priming enhances the mineralization potential of mesenchymal stem cells in vitro
      while also allowing for vessel formation.
AB  - Chondrogenic priming (CP) of mesenchymal stem cells (MSCs) and coculture of MSCs
      with human umbilical vein endothelial stem cells (HUVECs) both have been shown to
      significantly increase the potential for MSCs to undergo osteogenic
      differentiation and mineralization in vitro and in vivo. Such strategies mimic
      cartilage template formation or vascularization that occur during endochondral
      ossification during early fetal development. However, although both
      chondrogenesis and vascularization are crucial precursors for bone formation by
      endochondral ossification, no in vitro bone tissue regeneration strategy has
      sought to incorporate both events simultaneously. The objective of this study is
      to develop an in vitro bone regeneration strategy that mimics critical aspects of
      the endochondral ossification process, specifically (1) the formation of a
      cartilage template and (2) subsequent vascularization of this template. We
      initially prime the MSCs with chondrogenic growth factors, to ensure the
      production of a cartilage template, and subsequently implement a coculture
      strategy involving MSC and HUVECs. Three experimental groups were compared; (1)
      CP for 21 days with no addition of cells; (2) CP for 21 days followed by
      coculture of HUVECs (250,000 cells); (3) CP for 21 days followed by coculture of
      HUVECs and MSCs (250,000 cells) at a ratio of 1:1. Each group was cultured for a
      further 21 days in osteogenic media after the initial CP period. Biochemical
      (DNA, Alkaline Phosphatase Activity, Calcium, and Vessel Endothelial Growth
      Factor) and histological analyses (Alcian blue, alizarin red, CD31(+), and
      collagen type X) were performed 1, 2, and 3 weeks after the media switch. The
      results of this study show that CP provides a cartilage-like template that
      provides a suitable platform for HUVEC and MSC cells to attach, proliferate, and
      infiltrate for up to 3 weeks. More importantly we show that the use of the
      coculture methodology, rudimentary vessels are formed within this cartilage
      template and enhanced the mineralization potential of MSCs. Taken together these
      results indicate for the first time that the application of both chondrogenic and
      vascular priming of MSCs enhances the mineralization potential of MSCs in vitro
      while also allowing the formation of immature vessels. 

PMID- 25588589
TI  - Pediatric cataract surgery in buphthalmos.
AB  - PURPOSE: The pediatric eye offers many inherent surgical difficulties and when
      associated with a large buphthalmic eyeball, acts as a challenging ground for
      cataract surgeons. The purpose of our study is to describe the surgical outcome
      of cataract surgery in 6 children with buphthalmos. METHODS: Eight eyes of 6
      children with congenital glaucoma (buphthalmos) underwent phacoaspiration with or
      without intraocular lens (IOL) implantation. Demographic data, history of
      glaucoma surgery, intraocular pressure, biometry, surgical steps, and
      intraoperative and surgical outcome were noted for all patients from medical
      records. Postoperative outcome in terms of IOL stability, centration, visual
      acuity, and intraocular pressure were evaluated. RESULTS: Pediatric cataract
      surgery was performed in 8 eyes with buphthalmos. Implantation of IOL was
      possible in 7/8 eyes. Primary posterior capsulorhexis (PPC) was done in 2/8 eyes.
      The IOL was implanted in the bag in 3 eyes and captured in 4 eyes. Decentration
      of IOL occurred in 100% of eyes where PPC was performed. Membranectomy for visual
      axis obscuration was done in 3 eyes. CONCLUSIONS: Standard IOLs remain stable and
      centered with endocapsular implantation or rhexis fixation of IOL after pediatric
      cataract surgery in buphthalmos. However, PPC should not be attempted in the same
      sitting, as it leads to decentration.

PMID- 25588591
TI  - Consecutive laser in situ keratomileusis and accelerated corneal crosslinking in
      highly myopic patients: preliminary results.
AB  - PURPOSE: To report the preliminary results of an evaluation of the safety and
      predictability of Lasik Xtra, a technique combining laser in situ keratomileusis
      (LASIK) and accelerated corneal crosslinking, in highly myopic patients. METHODS:
      In this consecutive comparative case series, 70 consecutive eyes undergoing LASIK
      for correction of high myopia (-8.00 D to -19.00 D manifest refractive spherical
      equivalent) were prospectively recruited and treated with Lasik Xtra and compared
      with a retrospective consecutive control group of 64 eyes who had undergone LASIK
      alone for correction of high myopia. The follow-up was 3 months. Outcome measures
      included uncorrected distance visual acuity (UDVA), corrected distance visual
      acuity (CDVA), and refraction. RESULTS: A total of 61% of LASIK only eyes
      achieved UDVA of 20/25 or better, compared to 98% of Lasik Xtra eyes (p<0.001) at
      3 months. A greater percentage of eyes were within +/-0.50 of the intended
      correction in the Lasik Xtra group (88%) than in the LASIK only group (65%) at 3
      months (p = 0.005). Linear regression of the scatterplot of attempted versus
      achieved correction reveals a coefficient of determination of 0.83 in the LASIK
      only group vs 0.99 in the Lasik Xtra group. A trend (p = 0.051) towards greater
      refractive drift in the LASIK group (-0.13 D) vs the Lasik Xtra group (-0.04 D)
      was observed. No adverse events were observed in either group. CONCLUSIONS: Lasik
      Xtra did not reduce the refractive accuracy of the LASIK procedure. The addition
      of crosslinking may induce early stabilization of the cornea after LASIK,
      improving the predictability of refractive outcomes in highly myopic subjects.

PMID- 25588590
TI  - Effect of continuous ultrasonic phacoemulsification with anterior chamber
      maintainer on corneal endothelial damage in hard nuclear cataract.
AB  - PURPOSE: To study the effects of continuous ultrasonic phacoemulsification
      performed with and without an anterior chamber maintainer (ACM) on corneal
      endothelial damage in patients with hard nuclear cataract. METHODS: Sixty eyes in
      60 patients with hard nuclear cataract (grade IV), one lesion per eye, were
      randomly allocated into 2 groups: continuous ultrasonic phacoemulsification with
      (group A) or without (group B) ACM. The intraoperative accumulated energy complex
      parameter (AECP), frequency of shallow anterior chamber, and postoperative
      corneal incision edema, corneal endothelial cell counts, and visual recovery were
      compared between the groups. RESULTS: The intraoperative AECP, postoperative
      corneal incision edema, and postoperative visual recovery showed no significant
      differences between the groups (p>0.05). At 1 month postoperatively, the corneal
      endothelial cell loss rate and hexagonal cell percentage (postoperative compared
      to preoperative) in groups A and B were 0.117 +/- 0.12 and 9.97 +/- 9.52% and
      0.15 +/- 0.73 and 8.5 +/- 4.60%, respectively, with no significant difference
      noted (p>0.05). The endothelial cell mutation rate was significantly lower in
      group A than in group B at 6.41 +/- 6.78% and 28.27 +/- 27.95%, respectively
      (p<0.05). The frequency of intraoperative shallow anterior chamber was
      significantly lower in group A than in group B (2 vs 17 times, p<0.05).
      CONCLUSIONS: Continuous ultrasonic phacoemulsification with ACM is a safe,
      effective, simple, and easy method to treat hard nuclear cataract and causes
      minimal damage to corneal endothelial cells. It is an ideal surgical option and
      is worth popularizing.

PMID- 25588592
TI  - Circulating dipeptidyl peptidase-4 activity is associated with diabetic
      retinopathy in type 1 diabetic patients.
AB  - PURPOSE: Diabetic retinopathy (DR) is the most frequent complication among
      patients with type 1 diabetes mellitus (T1DM). Dipeptidyl peptidase-4 (DPP4) is a
      protease with elevated activity in patients with T1DM. Several studies indicate
      that DPP4 inhibitors might have beneficial effect on nonproliferative retinopathy
      (NPR) development as well as on its progression to proliferative retinopathy
      (PR). We aimed to explore the relationship between serum DPP4 activity and DR in
      patients with T1DM. METHODS: This cross-sectional study recruited 44 patients
      with T1DM. The DPP4 activity was measured by colorimetric assay in a microplate
      reader. Photodocumented retinopathy status was made according to the EURODIAB
      protocol. RESULTS: A total of 28 (63.6%) patients were men, mean age 45.36 years,
      diabetes duration 23.71 years, glycated hemoglobin A1c (HbA1c) 7.4%. Patients
      were stratified into 2 groups according to retinopathy prevalence. Group 1
      comprised 14 (31.85%) patients with DR absence while the second group consisted
      of 30 (68.15%) patients with both PR and NPR. Group 1 had lower fasting serum
      DPP4 activity (25.85 vs 33.84 U/L, p<0.001) when compared to the second group. In
      the binary logistic regression model adjusted for age, sex, diabetes duration,
      and HbA1c level, DPP4 activity was associated with DR prevalence (odds ratio
      1.887 [1.073-3.321]). CONCLUSIONS: Serum DPP4 activity may be independently
      associated with both DR types in patients with T1DM. Further study is warranted
      to elucidate whether there is an association between DPP4 activity and DR
      severity and/or progression.

PMID- 25588593
TI  - Macular buckling in optic disc pit maculopathy in association with the origin of
      macular elevation: 13-year mean postoperative results.
AB  - PURPOSE: To discuss the anatomical and functional results in cases of optic disc
      pit maculopathy (ODP-M) with a follow-up of at least 11 years after scleral
      buckling procedure (SBP). METHODS: We studied 12 eyes with ODP-M treated with
      SBP, in a long-term follow-up of 12.8 +/- 1.5 years after surgery. All patients
      underwent best-corrected visual acuity (BCVA) measurement, slit-lamp
      biomicroscopy, fundus photography, fluorescein angiography, indocyanine green
      angiography, B-scan ultrasonography, and optical coherence tomography at baseline
      and 6-12 months, 2 years and at least 11 years postoperatively. RESULTS: Complete
      macular reattachment was noticed between 6 and 12 months postoperatively. The
      BCVA improved significantly at the first postoperative examination. Further
      improvement was noticed at the second examination, while BCVA remained almost
      stable at the last examination. Foveal restoration of ellipsoid layer (inner
      segment/outer segment) was noted in 10 out of 12 cases. The existing vitreous
      strands remained unchanged during the follow-up. Vitreous traction gradually
      disappeared (4/5 eyes). Circulation in short/long posterior ciliary arteries was
      unaffected, while neither recurrences nor complications were observed during the
      follow-up period. Association of the scleral sponge to the scleral sheath of the
      optic nerve remained unchanged during the follow-up. CONCLUSIONS: A total of 12.8
      +/- 1.5 years after treatment, all the studied cases retained the successful
      anatomical and functional results that they had 2 years postoperatively, without
      inducing cataract during the follow-up period. The SBP seems to act equally well
      as a barrier either obstructing the entrance of fluid from the vitreous cavity or
      blocking the circulation of subarachnoid cerebrospinal fluid into the retina.

PMID- 25588594
TI  - Retrobulbar dexmedetomidine decreases the MLAC of ropivacaine in vitreoretinal
      surgery in children.
AB  - PURPOSE: Dexmedetomidine can prolong the duration of local anesthetics, but the
      effect of retrobulbar dexmedetomidine on the potency of ropivacaine for
      retrobulbar block has not been investigated. Our study was designed to determine
      the effect of retrobulbar dexmedetomidine on ropivacaine for retrobulbar block in
      children. METHODS: A group of 90 children aged 10-16 years scheduled for
      vitreoretinal surgery who received retrobulbar block were randomly assigned to 1
      of 3 groups: group L (retrobulbar ropivacaine), group LD1 (ropivacaine plus 0.5
      ug.kg-1 dexmedetomidine), or group LD2 (ropivacaine plus 1 ug.kg-1
      dexmedetomidine). The minimum local anesthetic concentration (MLAC) was
      determined according to a Dixon-Massey protocol. The primary endpoint of the
      study was MLAC. Secondary outcomes were duration of postoperative analgesia,
      postoperative pain scores, dexmedetomidine side effects, and time to hospital
      discharge. RESULTS: The MLAC values of retrobulbar ropivacaine were 0.314%,
      0.259%, and 0.246% in groups L, LD1, and LD2, respectively. The median
      (interquartile range) durations of analgesia in the postoperative period were 66
      (54-117), 89 (40-157), and 168 (120-194) minutes in groups L, LD1, and LD2,
      respectively (L vs LD1 or LD2, p<0.05). Wake-up time was significantly increased
      in groups LD1 and LD2. CONCLUSIONS: Retrobulbar dexmedetomidine reduces the MLAC
      values of ropivacaine and improves postoperative analgesia in children without
      any neurologic side effects.

PMID- 25588595
TI  - Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a
      pharmacovigilance study of 27 467 patients taking rivaroxaban.
AB  - BACKGROUND: In nonvalvular atrial fibrillation (NVAF), rivaroxaban is used to
      prevent stroke and systemic embolism. OBJECTIVE: To evaluate major bleeding (MB)
      in NVAF patients treated with rivaroxaban in a real-world clinical setting.
      METHODS: From January 1, 2013, to March 31, 2014, US Department of Defense
      electronic health care records were queried to describe MB rates and
      demographics. Major bleeding was identified using a validated algorithm. RESULTS:
      Of 27 467 patients receiving rivaroxaban, 496 MB events occurred in 478 patients,
      an incidence of 2.86 per 100 person-years (95% confidence interval: 2.61-3.13).
      The MB patients were older, mean (SD) age of 78.4 (7.7) vs 75.7 (9.7) years,
      compared with non-MB patients. Patients with MB had higher rates of hypertension
      (95.6% vs 75.8%), coronary artery disease (64.2% vs 36.7%), heart failure (48.5%
      vs 23.7%), and renal disease (38.7% vs 16.7%). Of MB patients, 63.2% were taking
      20 mg, 32.2% 15 mg, and 4.6% 10 mg of rivaroxaban. Four percent of MB patients
      took warfarin within the prior 30 days. Major bleeding was most commonly
      gastrointestinal (88.5%) or intracranial (7.5%). Although 46.7% of MB patients
      received a transfusion, none had sufficient evidence of receiving any type of
      clotting factor. Fourteen died during their MB hospitalization, yielding a fatal
      bleeding incidence rate of 0.08 per 100 person-years (95% confidence interval:
      0.05-0.14). Mean age at death was 82.4 years. CONCLUSIONS: In this large
      observational study, the MB rate was generally consistent with the registration
      trial results, and fatal bleeds were rare.

PMID- 25588596
TI  - Association between blood erythrocyte lead concentrations and hemoglobin levels
      in preschool children.
AB  - Despite decades of intensive research, lead (Pb) toxicity still remains one of
      the most frequently investigated subjects in environmental health. Whole blood
      lead (BPb) is usually used to evaluate Pb exposure for both screening and
      clinical diagnosis. However, it is generally recognized that BPb is not a
      sensitive biomarker for Pb exposure in hematological studies. Considering
      hematocrit (HCT) variation in different situations, HCT-adjusted BPb or
      erythrocyte Pb (EPb) may be more relevant when evaluating the hematotoxicity of
      blood Pb. Data collected from 855 preschool children, 3-7 years of age, allowed
      us to examine the relationship between EPb and hemoglobin (Hb) levels.
      Multivariate linear regression was performed to determine the significance of EPb
      as predictor of Hb after covariate adjustment; then, mean differences of Hb
      levels between quartiles of EPb and BPb (1st quartile as reference) were
      determined using ANOVA followed by Student's t test. The dose-response curve
      between EPb and HCT was plotted using locally weighted scatterplot smoothing
      (LOWESS) method. A doubling of EPb was associated with a 2.44 g/L decrease in Hb
      level. Compared to the 1st quartile group of EPb, the 3rd and 4th quartile groups
      showed significant decreases in Hb levels (3.01 and 3.97 g/L, respectively).
      Compared to the 1st quartile group of BPb, the 2nd quartile group showed a
      decrease in Hb levels (0.63 g/L), while the 3rd and 4th quartile groups showed
      increases in Hb levels (0.78 and 1.45 g/L, respectively). Increased EPb levels
      are significantly associated with decreased Hb levels in preschool children. HCT
      must be taken into consideration in investigating the hematological effects of
      Pb. Compared to BPb, EPb or HCT-adjusted BPb appear as a more effective biomarker
      to interpret the hematotoxicity of lead. Furthermore, blood erythrocytes are not
      only a repository of Pb but also a primary target of its toxicity.

PMID- 25588598
TI  - The photosensitized oxidation of mixture of parabens in aqueous solution.
AB  - The work presents results of studies on the photosensitized oxidation of mixture
      of five parabens (methyl-, ethyl-, propyl-, n-butyl-, and benzylparaben) in
      aqueous solution. Aluminum phthalocyanine chloride tetrasulfonic acid and xenon
      lamp simulating solar radiation were used as a photosensitizer and a light
      source, respectively. The purpose was to investigate the influence of inhibitory
      effect compounds present in the mixture on the reaction rate. The influence of
      the addition of second photosensitizer on the parabens degradation rate was
      investigated. The effect of additives: tert-butanol - hydroxyl radical scavenger
      and sodium azide - singlet oxygen scavenger on reaction course was also
      determined. The transformation products formed during the photosensitized
      oxidation process were analyzed by UPLC-MS/MS. The efficiency of photosensitized
      oxidation of parabens with natural sunlight irradiation in the central Poland was
      checked.

PMID- 25588597
TI  - Occurrence of polychlorinated diphenyl ethers in Nanjing section of the Yangtze
      River: level and distribution pattern.
AB  - Polychlorinated diphenyl ethers (PCDEs) are a group of halogenated aromatic
      compounds and serious environmental pollutants. In the present study, sediment
      and water samples from eight sites in Nanjing section of the Yangtze River were
      characterized with 15 congeners of PCDEs. Concentrations and distributions of
      these PCDEs in water phase and sediments were analyzed by GC/MS. Results
      demonstrated that ?PCDE concentrations were higher in the low water period (1.15
      1.80 MUg/L) than those in the high water period (0.73-1.30 MUg/L) in water phase.
      Moreover, ?PCDE concentrations were higher in the low water period (1.58-3.98
      MUg/kg) than those in the high water period (1.24-3.48 MUg/kg) in sediments. A
      significant linear relationship existed between the ?PCDE concentrations and TOC
      contents in sediments, but a poor linearity was found between ?PCDE
      concentrations and DOC contents in water phase. Furthermore, the comparison of
      the percentage compositions in sediments and in water phase showed that CDE-30
      (2,4,6-tri-CDE) was the predominant congener in the studied sites, and higher
      chlorinated congeners accounted for a larger proportion in sediments than those
      in water phase. In conclusion, the present study demonstrated the prevalent
      contamination by PCDEs in sediments and water from the Nanjing section of the
      Yangtze River.

PMID- 25588599
TI  - Uncertainty assessment of water quality modeling for a small-scale urban
      catchment using the GLUE methodology: a case study in Shanghai, China.
AB  - There is often great uncertainty in water quality modeling for urban drainage
      systems because water quality variation in systems is complex and affected by
      many factors. The stormwater management model (SWMM) was applied to a small-scale
      urban catchment with a simple and well-maintained stormwater drainage system
      without illicit connections. This was done to assess uncertainty in build-up and
      wash-off modeling of pollutants within the generalized likelihood uncertainty
      estimation (GLUE) methodology, based on a well-calibrated water quantity model.
      The results indicated great uncertainty of water quality modeling within the GLUE
      methodology. Comparison of uncertainties in various pollutant build-up and wash
      off models that were available in SWMM indicated that those uncertainties varied
      slightly. This may be a consequence of the specific characteristics of rainfall
      events and experimental sites used in the study. The uncertainty analysis of
      water quality parameters in SWMM is conducive to effectively evaluating model
      reliability, and provides an experience base for similar research and
      applications.

PMID- 25588600
TI  - New abietane-type diterpene glycosides from the roots of Tripterygium wilfordii.
AB  - Two new abietane diterpene glycosides, wilfordosides A (1) and B (2), were
      isolated from the roots of Tripterygium wilfordii. The structures of compounds 1
      and 2 were established using spectroscopic methods including extensive 1D and 2D
      NMR analysis, in combination with chemical reactions. 

PMID- 25588602
TI  - Zoonotic origin of hepatitis E.
AB  - The concept of zoonotic viral hepatitis E has emerged a few years ago following
      the discovery of animal strains of hepatitis E virus (HEV), closely related to
      human HEV, in countries where sporadic cases of hepatitis E were autochthonous.
      Recent advances in the identification of animal reservoirs of HEV have confirmed
      that strains circulating in domestic and wild pigs are genetically related to
      strains identified in indigenous human cases. The demonstration of HEV
      contamination in the food chain or pork products has indicated that HEV is
      frequently a foodborne zoonotic pathogen. Direct contacts with infected animals,
      consumption of contaminated animal meat or meat products are all potential means
      of zoonotic HEV transmission. The recent identification of numerous other
      genetically diverse HEV strains from various animal species poses additional
      potential concerns for HEV zoonotic infection. 

PMID- 25588604
TI  - Information seeking in capuchins (Cebus apella): a rudimentary form of
      metacognition?
AB  - In previous research, great apes and rhesus macaques have demonstrated multiple
      apparently metacognitive abilities, whereas capuchin monkeys have not. The
      present experiment investigated whether at least a rudimentary form of
      metacognition might be demonstrated in capuchins if a simplified metacognitive
      task was used. Capuchins (Cebus apella) were required to locate a food reward
      hidden beneath one of two inverted cups that sat on a Plexiglas tray. In some
      conditions, the capuchins were shown where the food was hidden, in others they
      could infer its location, and in yet others they were not given information about
      the location of the food. On all trials, capuchins could optionally seek
      information about the food's location by looking up through the Plexiglas beneath
      the cups. In general, capuchins did this less often when they were shown the food
      reward, but not when they could infer the reward's location. These data suggest
      that capuchins-if metacognitive-only metacognitively control their information
      seeking in some conditions, particularly those in which information is presented
      in the visual domain. This may represent a rudimentary version of metacognitive
      control, in comparison with that seen in great apes and humans.

PMID- 25588603
TI  - Investigation of next-generation sequencing technologies as a diagnostic tool for
      amyotrophic lateral sclerosis.
AB  - The future of genetic diagnostics will see a move toward massively parallel next
      generation sequencing of a patient's DNA. Amyotrophic lateral sclerosis (ALS) is
      one of the diseases that would benefit from this prospect. Exploring this idea,
      we designed a screening panel to sequence 25 ALS-linked genes and examined
      samples from 95 patients with both familial and sporadic ALS. Forty-three rare
      polymorphisms were detected in this cohort. A third of these have already been
      reported with respect to ALS, leaving 28 novel variants all open for further
      investigation. This study highlights the potential benefits of next-generation
      sequencing as a reliable, cost and time efficient, diagnostic, and research tool
      for ALS. 

PMID- 25588605
TI  - Z-estimation and stratified samples: application to survival models.
AB  - The infinite dimensional Z-estimation theorem offers a systematic approach to
      joint estimation of both Euclidean and non-Euclidean parameters in probability
      models for data. It is easily adapted for stratified sampling designs. This is
      important in applications to censored survival data because the inverse
      probability weights that modify the standard estimating equations often depend on
      the entire follow-up history. Since the weights are not predictable, they
      complicate the usual theory based on martingales. This paper considers joint
      estimation of regression coefficients and baseline hazard functions in the Cox
      proportional and Lin-Ying additive hazards models. Weighted likelihood equations
      are used for the former and weighted estimating equations for the latter.
      Regression coefficients and baseline hazards may be combined to estimate
      individual survival probabilities. Efficiency is improved by calibrating or
      estimating the weights using information available for all subjects. Although
      inefficient in comparison with likelihood inference for incomplete data, which is
      often difficult to implement, the approach provides consistent estimates of
      desired population parameters even under model misspecification. 

PMID- 25588606
TI  - Child impact on family functioning: a multivariate analysis in multiplex families
      with children and mothers both affected by attention-deficit/hyperactivity
      disorder (ADHD).
AB  - ADHD seriously impacts family functioning, even the more in families with
      simultaneous parental and child ADHD. The aim of the study was to examine
      associations between family impact of child ADHD and child, mother and family
      characteristics in multiplex families with children and mothers both affected by
      ADHD. One hundred and forty-four mother-child pairs were assessed (children: mean
      age 9.4 +/- 1.7 years, 73.6 % male). Family impact of child ADHD was rated by
      mothers using the Family Impact Questionnaire (FIQ). Multiple linear regression
      analyses were performed with child and maternal psychopathology and basic family
      characteristics such as employment, partnership status and number of children as
      predictors and FIQ subscores as criteria. Rates of variance explained by family
      variables were 49 % for negative feelings towards the child, 37 % for impact on
      partnership, 31 % for impact on social life and 27 % for impact on finances (p <
      .001, respectively). Pearson correlations with family impact were especially
      strong for child externalizing symptoms, maternal ADHD and co-morbid symptoms of
      the mother. The strongest independent predictor was oppositional defiant child
      behaviour. In ADHD multiplex families, mothers' perception of the impact of an
      ADHD child on its family can be explained to a substantial degree by child
      psychopathology, maternal psychopathology and basic family characteristics.
      Although a cross-sectional design does not allow for causal interpretations, the
      findings of this study offer important targets for the treatment of ADHD in a
      family context pointing to the need for assessing and treating parental mental
      health and co-morbid symptoms besides ADHD core symptoms. 

PMID- 25588607
TI  - pH dependence of cadmium-contaminated drinking water on the development of
      cardiovascular injury in Wistar rats.
AB  - The purpose of our study was to investigate the effect of water pH in the genesis
      of cardiovascular injury caused by cadmium poisoning. For this study, 90 male
      Wistar rats were used, divided into six groups: A, 15 rats that received 400 mg/l
      cadmium chloride (CdCl2) in drinking water at a neutral pH of 7.0; B, 15 rats
      that received CdCl2 (400 mg/l) in drinking water at an acidic pH of 5.0; C, 15
      rats that received CdCl2 (400 mg/l) in drinking water at a basic pH of 8.0; D, 15
      rats that received water at an acidic pH of 5.0; E, 15 rats that received water
      at a basic pH of 8.0; and F, 15 rats that received water at a neutral pH of 7.0.
      All animals were euthanized after 6 months. We collected the heart and aorta from
      each rat for microscopic analysis. No microscopic changes were observed in the
      hearts. In the aorta, fatty streaks appeared in a large proportion of animals in
      groups A (50 %) and B (46 %), but fatty streaks appeared in a smaller minority of
      animals in groups C (15.3 %), D (0 %), E (7 %), and F (13.3 %) (p < 0.05).
      Cadmium exposure caused the development of fatty streaks in the aorta of animals
      and the exposure to this metal in basic pH decreased the formation of these
      lesions.

PMID- 25588608
TI  - Luminescent cation sensors: from host-guest chemistry, supramolecular chemistry
      to reaction-based mechanisms.
AB  - Other than traditional cation detection strategies, which are solely based on the
      ion-receptor complementarity, the extension of the concept of supramolecular
      chemistry and the mechanisms of irreversible analyte-specific reactions have also
      been integrated into the design of luminescent probes for the detection of cation
      in view of the exploration of highly sensitive and selective sensors. In this
      highlight, a versatile range of organic and organometallic architectures with
      cation-sensing capabilities based on the above mechanisms will be discussed. 

PMID- 25588609
TI  - A fractal-like electrode based on double-wall nanotubes of anatase exhibiting
      improved electrochemical behaviour in both lithium and sodium batteries.
AB  - An anatase nanotube array has been prepared with a special morphology: two
      concentric walls and a very small central cavity. The method used here to achieve
      the double-wall structure is a single-step anodization process under a voltage
      ramp. Thanks to this nanostructure, which is equivalent to a fractal electrode,
      the electrochemical behaviour is improved, and the specific capacity is higher in
      both lithium and sodium cells due to pseudocapacitance. The double-wall structure
      of the nanotube enhances the surface of TiO2 being in contact with the
      electrolyte solution, thus allowing an easy penetration of the alkali ions into
      the electrode active material. The occurrence of sodium titanate in the electrode
      material after electrochemical reaction with sodium is studied by using EPR,
      HRTEM and NMR experiments. 

PMID- 25588610
TI  - Mental health and psychosocial functioning in adolescence: an investigation among
      Indian students from Delhi.
AB  - While developmental studies predominantly investigated adolescents' mental
      illness and psychosocial maladjustment, the present research focused on positive
      mental health of Indian adolescents within the Mental Health Continuum model.
      Aims were to estimate their prevalence of mental health and to examine its
      associations with mental distress and psychosocial functioning, taking into
      account age and gender. A group of 539 students (age 13-18; 43.2% girls) in the
      National Capital Territory of Delhi completed Mental Health Continuum Short Form,
      Depression Anxiety and Stress Scales-21, Strengths and Difficulties
      Questionnaire. Findings showed that 46.4% participants were flourishing, 51.2%
      were moderately mentally healthy, and only 2.4% were languishing. A higher number
      of girls and younger adolescents were flourishing compared to boys and older
      adolescents. Moreover, flourishing youths reported lower prevalence of depression
      and adjustment difficulties, and more prosocial behavior. Findings support the
      need to expand current knowledge on positive mental health for well-being
      promotion in adolescence. 

PMID- 25588611
TI  - A comparative study of patients' attitudes toward clinical research in the United
      States and urban and rural China.
AB  - As the number of clinical trials conducted in China increases, understanding
      Chinese attitudes toward clinical research is critical for designing effective
      and ethical studies. Two survey studies were conducted in 2012 and 2013 to
      compare patient attitudes toward clinical research and factors affecting research
      participation in the United States and urban and rural China. We surveyed 525
      patients in 2012 (186 US, 186 urban, 153 rural China) and 690 patients in 2013
      (412 US, 206 urban, 72 rural China). US patients were more likely to have no
      concerns regarding research participation than Chinese patients. Most common
      concerns of US patients were safety, privacy and confidentiality, and time
      required. Safety was a top concern for many Chinese. Chinese patients,
      particularly rural Chinese, were more concerned about the likelihood of self
      benefit, and receiving free medical care and financial incentive had greater
      influence on their participation. Being informed of the freedom to choose whether
      to participate or to leave a study was less important to Chinese patients. Our
      study provides important insights into Chinese patients' attitudes toward
      clinical research and the need to educate them about their rights. These findings
      help in designing cross-cultural clinical studies that maximize enrollment while
      upholding Western ethical standards.

PMID- 25588612
TI  - Testing for clustering at many ranges inflates family-wise error rate (FWE).
AB  - BACKGROUND: Testing for clustering at multiple ranges within a single dataset is
      a common practice in spatial epidemiology. It is not documented whether this
      approach has an impact on the type 1 error rate. METHODS: We estimated the family
      wise error rate (FWE) for the difference in Ripley's K functions test, when
      testing at an increasing number of ranges at an alpha-level of 0.05. Case and
      control locations were generated from a Cox process on a square area the size of
      the continental US (~3,000,000 mi2). Two thousand Monte Carlo replicates were
      used to estimate the FWE with 95% confidence intervals when testing for
      clustering at one range, as well as 10, 50, and 100 equidistant ranges. RESULTS:
      The estimated FWE and 95% confidence intervals when testing 10, 50, and 100
      ranges were 0.22 (0.20 - 0.24), 0.34 (0.31 - 0.36), and 0.36 (0.34 - 0.38),
      respectively. CONCLUSIONS: Testing for clustering at multiple ranges within a
      single dataset inflated the FWE above the nominal level of 0.05. Investigators
      should construct simultaneous critical envelopes (available in spatstat package
      in R), or use a test statistic that integrates the test statistics from each
      range, as suggested by the creators of the difference in Ripley's K functions
      test.

PMID- 25588613
TI  - The sleep loss epidemic: hunting ninjas in the dark.

PMID- 25588614
TI  - The VPS-20 subunit of the endosomal sorting complex ESCRT-III exhibits an open
      conformation in the absence of upstream activation.
AB  - Members of the endosomal sorting complex required for transport (ESCRT) machinery
      function in membrane remodelling processes during multivesicular endosome (MVE)
      biogenesis, cytokinesis, retroviral budding and plasma membrane repair. During
      luminal vesicle formation at endosomes, the ESCRT-II complex and the ESCRT-III
      subunit vacuolar protein sorting (VPS)-20 play a specific role in regulating
      assembly of ESCRT-III filaments, which promote vesicle scission. Previous work
      suggests that Vps20 isoforms, like other ESCRT-III subunits, exhibits an auto
      inhibited closed conformation in solution and its activation depends on an
      association with ESCRT-II specifically at membranes [1]. However, we show in the
      present study that Caenorhabditis elegans ESCRT-II and VPS-20 interact directly
      in solution, both in cytosolic cell extracts and in using recombinant proteins in
      vitro. Moreover, we demonstrate that purified VPS-20 exhibits an open extended
      conformation, irrespective of ESCRT-II binding, in contrast with the closed auto
      inhibited architecture of another ESCRT-III subunit, VPS-24. Our data argue that
      individual ESCRT-III subunits adopt distinct conformations, which are tailored
      for their specific functions during ESCRT-mediated membrane reorganization
      events. 

PMID- 25588615
TI  - Effects of inoculation of commercial starter cultures on the quality and
      histamine accumulation in fermented sausages.
AB  - To meet the requirements of high-quality safe products, starter cultures are used
      to produce fermented sausages. The effects of 3 commercial starter cultures,
      namely SM-194, T-SPX, and SM-181, on histamine accumulation and quality
      parameters including microbial quality, pH, water activity, and total volatile
      base nitrogen, as well as the color and texture properties, were evaluated during
      the fermentation and ripening of fermented sausages. Although initial counts of
      Escherichia coli, Enterobacteriaceae, and Pseudomonas were similar in the 4
      batches, the growth of these microorganisms was significantly inhibited (P <
      0.05) in batches SM-194, T-SPX, and SM-181 throughout the fermentation and
      ripening period. The counts of E. coli, Enterobacteriaceae, and Pseudomonas
      increased to maximum levels of 3.89, 4.41, and 5.15 log10 colony forming units/g
      in the control sausages, respectively. At the end of ripening, the levels of
      histamine were 8.85, 0.32, 7.82, and 3.18 mg/kg for batches C, SM-194, T-SPX, and
      SM-181, respectively. The results revealed that commercial starter cultures,
      particularly starter cultures SM-194 and SM-181, made a great contribution to
      histamine reduction. In addition, batches inoculated with starter cultures showed
      a stronger acidification and lower level of total volatile base nitrogen than the
      control sample during production (P < 0.05). In conclusion, it seems that the
      inoculation of commercial starter cultures, particularly starter cultures SM-194
      and SM-181, contributes to improving microbial quality, hygienic quality and food
      safety of fermented sausages. 

PMID- 25588617
TI  - Threshold for NIH stroke scale in predicting vessel occlusion and functional
      outcome after stroke thrombolysis.
AB  - BACKGROUND: Data are limited on optimal threshold for baseline National
      Institutes of Health Stroke Scale in predicting outcome after stroke thrombolysis
      (intravenous thrombolysis). AIMS: Finding thresholds for baseline National
      Institutes of Health Stroke Scale scores that predict functional outcome and
      baseline vessel occlusion. METHODS: We analyzed 44 331 patients with available
      modified Rankin Scale score at three-months and 11 632 patients with computed
      tomography/magnetic resonance angiography documented vessel occlusion at baseline
      in the SITS-International Stroke Thrombolysis Register. Main outcomes were
      functional independency (modified Rankin Scale 0-2) at three-months and baseline
      vessel occlusion. We obtained area under the curves by receiver operating
      characteristic analysis and calculated multivariately adjusted odds ratio for the
      outcomes of interest based on baseline National Institutes of Health Stroke Scale
      scores. RESULTS: For functional independency, National Institutes of Health
      Stroke Scale scores of 12 (area under the curve 0.775) and for baseline vessel
      occlusion, scores of 11 (area under the curve 0.678) were optimal threshold
      values. For functional independency, adjusted odds ratio decreased to 0.07 (95%
      CI 0.05-0.11), and for presence of baseline occlusion, aOR increased to 3.28 (95%
      CI 3.04-3.58) for National Institutes of Health Stroke Scale scores 12 and 11,
      respectively, compared with National Institutes of Health Stroke Scale score 0.
      National Institutes of Health Stroke Scale thresholds decreased with time from
      stroke onset to imaging, with 2-3 points, respectively, if time to imaging
      exceeded three-hours. CONCLUSIONS: Ideally, all acute stroke patients should have
      immediate access to multimodal imaging. In reality these services are limited.
      Baseline National Institutes of Health Stroke Scale scores of 11 and 12 were
      identified as markers of baseline vessel occlusion and functional independency
      after intravenous thrombolysis, respectively. These values are time dependent;
      therefore, a threshold of National Institutes of Health Stroke Scale 9 or 10
      points may be considered in the prehospital selection of patients for immediate
      transfer to centers with multimodal imaging and availability of highly
      specialized treatments.

PMID- 25588616
TI  - Ligand-based 3D QSAR analysis of reactivation potency of mono- and bis-pyridinium
      aldoximes toward VX-inhibited rat acetylcholinesterase.
AB  - To predict unknown reactivation potencies of 12 mono- and bis-pyridinium
      aldoximes for VX-inhibited rat acetylcholinesterase (rAChE), three-dimensional
      quantitative structure-activity relationship (3D QSAR) analysis has been carried
      out. Utilizing molecular interaction fields (MIFs) calculated by molecular
      mechanical (MMFF94) and quantum chemical (B3LYP/6-31G*) methods, two satisfactory
      ligand-based CoMFA models have been developed: 1. R(2)=0.9989, Q(LOO)(2)=0.9090,
      Q(LTO)(2)=0.8921, Q(LMO(20%))(2)=0.8853, R(ext)(2)=0.9259, SDEP(ext)=6.8938; 2.
      R(2)=0.9962, Q(LOO)(2)=0.9368, Q(LTO)(2)=0.9298, Q(LMO(20%))(2)=0.9248,
      R(ext)(2)=0.8905, SDEP(ext)=6.6756. High statistical significance of the 3D QSAR
      models has been achieved through the application of several data noise reduction
      techniques (i.e. smart region definition SRD, fractional factor design FFD,
      uninformative/iterative variable elimination UVE/IVE) on the original MIFs.
      Besides the ligand-based CoMFA models, an alignment molecular set constructed by
      flexible molecular docking has been also studied. The contour maps as well as the
      predicted reactivation potencies resulting from 3D QSAR analyses help better
      understand which structural features are associated with increased reactivation
      potency of studied compounds.

PMID- 25588618
TI  - Epigenetic modulation of metabolic decisions.
AB  - In the recent years there has been a tremendous increase in our understanding of
      chromatin, transcription and the importance of metabolites in their regulation.
      This review highlights what is currently sparse information that suggest
      existence of a refined system integrating metabolic and chromatin control. We
      indicate possible regulatory modes, such as feed forward amplification, that may
      help effect and stabilize long-lasting phenotypic decisions within and even
      across generations using adipogenesis as the primary context. 

PMID- 25588619
TI  - Does practice make perfect? Resident experience with breast surgery influences
      excision adequacy.
AB  - BACKGROUND: The adequacy of breast-conserving surgery (BCS) for invasive or in
      situ disease is largely determined by the final surgical margins. Although margin
      status is associated with various clinicopathologic features, the influence of
      resident involvement remains controversial. METHODS: Patients who underwent BCS
      for malignancy from 2009 to 2012 were identified. The effects of various
      clinicopathologic characteristics and resident involvement were evaluated.
      RESULTS: Of the 502 cases performed, a resident assisted with most surgeries
      (95%). The overall rate of positive margins was 30%, which was not associated
      with resident involvement. Interns assisting from July to September had
      significantly lower rates of positive margins. Margins were more likely to be
      positive following any given resident's first 3 cases on their breast rotation
      than throughout the remainder of their rotation. CONCLUSION: Although resident
      level alone does not influence the adequacy of BCS, experience gained over time
      does appear to be associated with lower rates of positive margins.

PMID- 25588620
TI  - Doing well by doing good: linking access with quality.
AB  - BACKGROUND: We hypothesize that medical centers that prioritize altruism can also
      deliver superior quality care. METHODS: Data were obtained from California's
      Office of Statewide Health Planning and Development, Medicare Hospital Compare,
      and the Joint Commission US Census Bureau's American Community Survey. Outcomes
      were measured using summary statistics, regression analysis, and quality indices.
      Total discounted revenue/total revenue (TDR/TR) served as a proxy for altruistic
      care. RESULTS: In nonprofit hospitals, TDR/TR positively correlated with 5
      quality indices including pneumonia (P < .001), heart failure (P = .05), and
      overall surgical process of care (P = .009). Hospital size predicted higher
      quality surgical process (P = .06, 201 to 300 beds; P = .01, >301 beds), hospital
      teaching status demonstrated positive correlation (beta = .048, P = .69), and
      poverty was negatively correlated (beta = -.00072, P = .89). Positive TDR/TR did
      not adversely affect mortality or readmission rates (P = .52). CONCLUSIONS:
      TDR/TR predicts quality in nonprofit hospitals without increasing mortality and
      readmission. Altruistic motivation may be associated with the delivery of higher
      quality surgical care.

PMID- 25588621
TI  - Appendectomy: a risk factor for colectomy in patients with Clostridium difficile.
AB  - BACKGROUND: The appendix, considered an intestinal microbiota reservoir, may be
      protective against the risk of fulminant Clostridium difficile infection.
      METHODS: Retrospective analysis was performed in patients with C. difficile
      infection at St. Francis Medical Center from 2007 to 2011. Outcome of infection
      and history of appendectomy were compared. Statistical analysis was by chi-square
      and multivariate logistic regression. RESULTS: In total, 507 patients were
      hospitalized for C. difficile. Of 388 patients with intact appendix, 20 (5.2%)
      developed fulminant infection and required colectomy, whereas of 119 patients
      with previous appendectomy, 13 (10.9%) required colectomy. An increased severity
      of disease, indicated by increased rate of colectomy, occurred for the group with
      a history of appendectomy (P = .03). Age and sex were adjusted by multivariant
      regression (P = .05). CONCLUSIONS: Appendectomy may be a risk factor for
      increased severity of C. difficile infection. Although the mechanism is unknown,
      further studies are warranted.

PMID- 25588623
TI  - Uncovering the role of cathode buffer layer in organic solar cells.
AB  - Organic solar cells (OSCs) as the third generation photovoltaic devices have
      drawn intense research, for their ability to be easily deposited by low-cost
      solution coating technologies. However the cathode in conventional OSCs, Ca, can
      be only deposited by thermal evaporation and is highly unstable in ambient.
      Therefore various solution processible cathode buffer layers (CBLs) are
      synthesized as substitute of Ca and show excellent effect in optimizing
      performance of OSCs. Yet, there is still no universal consensus on the mechanism
      that how CBL works, which is evidently a critical scientific issue that should be
      addressed. In this article detailed studies are targeted on the interfacial
      physics at the interface between active layer and cathode (with and without
      treatment of a polar CBL) by using ultraviolet photoelectron spectroscopy,
      capacitance-voltage measurement, and impedance spectroscopy. The experimental
      data demonstrate that CBL mainly takes effect in three ways: suppressing surface
      states at the surface of active layer, protecting the active layer from being
      damaged by thermally evaporated cathode, and changing the energy level alignment
      by forming dipole moments with active layer and/or cathode. Our findings here
      provide a comprehensive picture of interfacial physics in devices with and
      without CBL. 

PMID- 25588622
TI  - Insulin-like growth factor-1 endues monocytes with immune suppressive ability to
      inhibit inflammation in the intestine.
AB  - The pathogenesis of some chronic inflammation such as inflammatory bowel disease
      is unclear. Insulin-like growth factor-1 (IGF1) has active immune regulatory
      capability. This study aims to investigate into the mechanism by which IGF1
      modulates the monocyte (Mo) properties to inhibit immune inflammation in the
      intestine. In this study, the production of IGF1 by intestinal epithelial cells
      was evaluated by real time RT-PCR and Western blotting. Mos were analyzed by flow
      cytometry. A mouse colitis model was created with trinitrobenzene sulfonic acid.
      The results showed that mouse IECs produced IGF1, which could be up regulated by
      exposure to CpG-ODN (CpG-oligodeoxynueleotides) in the culture. Culture the CpG
      ODN-primed IEC cells and Mos or exposure of Mos to IGF1 in the culture induced
      the Mos to express IL-10. The IGF1-primed Mos showed the immune suppressive
      effect on inhibiting the immune inflammation in the mouse colon. In conclusion,
      the IGF1-primed Mos are capable of suppressing immune inflammation in the
      intestine. 

PMID- 25588624
TI  - Computational cancer biology: education is a natural key to many locks.
AB  - BACKGROUND: Oncology is a field that profits tremendously from the genomic data
      generated by high-throughput technologies, including next-generation sequencing.
      However, in order to exploit, integrate, visualize and interpret such high
      dimensional data efficiently, non-trivial computational and statistical analysis
      methods are required that need to be developed in a problem-directed manner.
      DISCUSSION: For this reason, computational cancer biology aims to fill this gap.
      Unfortunately, computational cancer biology is not yet fully recognized as a
      coequal field in oncology, leading to a delay in its maturation and, as an
      immediate consequence, an under-exploration of high-throughput data for
      translational research. Here we argue that this imbalance, favoring 'wet lab
      based activities', will be naturally rectified over time, if the next generation
      of scientists receives an academic education that provides a fair and competent
      introduction to computational biology and its manifold capabilities. Furthermore,
      we discuss a number of local educational provisions that can be implemented on
      university level to help in facilitating the process of harmonization.

PMID- 25588625
TI  - Implementation of evidence-based practice in relation to a clinical nursing
      ladder system: a national survey in Taiwan.
AB  - BACKGROUND: Although evidence-based practice (EBP) has been widely investigated,
      few studies have investigated its correlation with a clinical nursing ladder
      system. The current national study evaluates whether EBP implementation has been
      incorporated into the clinical ladder system. METHODS: A cross-sectional
      questionnaire survey was conducted nationwide of registered nurses among regional
      hospitals of Taiwan in January to April 2011. Subjects were categorized into
      beginning nurses (N1 and N2) and advanced nurses (N3 and N4) by the clinical
      ladder system. Multivariate logistic regression model was used to adjust for
      possible confounding demographic factors. RESULTS: Valid postal questionnaires
      were collected from 4,206 nurses, including 2,028 N1, 1,595 N2, 412 N3, and 171
      N4 nurses. Advanced nurses were more aware of EBP than beginning nurses (p <
      0.001; 90.7% vs. 78.0%). In addition, advanced nurses were more likely to hold
      positive beliefs about and attitudes toward EBP (p < 0.001) and possessed more
      sufficient knowledge of and skills in EBP (p < 0.001). Furthermore, they more
      often implemented EBP principles (p < 0.001) and accessed online evidence-based
      retrieval databases (p < 0.001). The most common motivation for using online
      databases was self-learning for advanced nurses and positional promotion for
      beginning nurses. Multivariate logistic regression analyses showed advanced
      nurses were more aware of EBP, had higher knowledge and skills of EBP, and more
      often implemented EBP than beginning nurses. LINKING EVIDENCE TO ACTION: The
      awareness of, beliefs in, attitudes toward, knowledge of, skills in, and
      behaviors of EBP among advanced nurses were better than those among beginning
      nurses. The data indicate that a clinical ladder system can serve as a useful
      means to enhance EBP implementation.

PMID- 25588626
TI  - Postpancreatoduodenectomy Hemorrhage Treated by Combined Transcatheter Arterial
      Embolization and Superior Mesenteric Artery to Iliac Artery Bypass: Report of a
      Case.
AB  - Postpancreatectomy hemorrhage is a potentially life-threatening complication. We
      report herein our experience with a 65-year-old man with locally advanced
      pancreatic adenocarcinoma who underwent pancreatoduodenectomy with
      lymphadenectomy following neoadjuvant chemoradiotherapy. On postoperative day 45,
      he developed massive hematemesis. Angiography revealed active bleeding from the
      common hepatic artery, and transcatheter coil embolization of that vessel was
      successfully performed. On postoperative day 64, he again developed massive
      hematemesis. Angiography revealed active bleeding from the proximal superior
      mesenteric artery. Immediately after coil embolization of that vessel, bypass
      grafting between the superior mesenteric artery and the right common iliac artery
      was performed, using a greater saphenous vein graft. The combination of
      embolization and bypass grafting is an option for treatment of bleeding from the
      superior mesenteric artery in an emergent situation. 

PMID- 25588627
TI  - Diabolical points in multi-scatterer optomechanical systems.
AB  - Diabolical points, which originate from parameter-dependent accidental
      degeneracies of a system's energy levels, have played a fundamental role in the
      discovery of the Berry phase as well as in photonics (conical refraction), in
      chemical dynamics, and more recently in novel materials such as graphene, whose
      electronic band structure possess Dirac points. Here we discuss diabolical points
      in an optomechanical system formed by multiple scatterers in an optical cavity
      with periodic boundary conditions. Such configuration is close to experimental
      setups using micro-toroidal rings with indentations or near-field scatterers. We
      find that the optomechanical coupling is no longer an analytic function near the
      diabolical point and demonstrate the topological phase arising through the
      mechanical motion. Similar to a Fabry-Perot resonator, the optomechanical
      coupling can grow with the number of scatterers. We also introduce a minimal
      quantum model of a diabolical point, which establishes a connection to the motion
      of an arbitrary-spin particle in a 2D parabolic quantum dot with spin-orbit
      coupling. 

PMID- 25588628
TI  - DNA barcoding largely supports 250 years of classical taxonomy: identifications
      for Central European bees (Hymenoptera, Apoidea partim).
AB  - This study presents DNA barcode records for 4118 specimens representing 561
      species of bees belonging to the six families of Apoidea (Andrenidae, Apidae,
      Colletidae, Halictidae, Megachilidae and Melittidae) found in Central Europe.
      These records provide fully compliant barcode sequences for 503 of the 571 bee
      species in the German fauna and partial sequences for 43 more. The barcode
      results are largely congruent with traditional taxonomy as only five closely
      allied pairs of species could not be discriminated by barcodes. As well, 90% of
      the species possessed sufficiently deep sequence divergence to be assigned to a
      different Barcode Index Number (BIN). In fact, 56 species (11%) were assigned to
      two or more BINs reflecting the high levels of intraspecific divergence among
      their component specimens. Fifty other species (9.7%) shared the same Barcode
      Index Number with one or more species, but most of these species belonged to a
      distinct barcode cluster within a particular BIN. The barcode data contributed to
      clarifying the status of nearly half the examined taxonomically problematic
      species of bees in the German fauna. Based on these results, the role of DNA
      barcoding as a tool for current and future taxonomic work is discussed. 

PMID- 25588629
TI  - Hybrid granular cell tumor/perineurioma.

PMID- 25588630
TI  - Myoepithelial carcinoma of soft tissue: a case report and review of the
      literature.

PMID- 25588631
TI  - Combined squamous cell carcinoma and follicular carcinoma of the thyroid.

PMID- 25588632
TI  - Primary leiomyosarcoma of adrenal gland with tissue eosinophilic infiltration.

PMID- 25588633
TI  - A Case of Type II Enteropathy-Associated T-Cell Lymphoma with Epstein-Barr Virus
      Positivity.

PMID- 25588634
TI  - Indolent CD56-Positive Clonal T-Cell Lymphoproliferative Disease of the Stomach
      Mimicking Lymphomatoid Gastropathy.

PMID- 25588635
TI  - A case of epithelioid blue nevus.

PMID- 25588636
TI  - Digital papillary carcinoma.

PMID- 25588637
TI  - Periductal stromal tumor of breast: a case report and a review of literature.

PMID- 25588638
TI  - A case of mixed adenoneuroendocrine carcinoma of the common bile duct: initially
      diagnosed as cholangiocarcinoma.

PMID- 25588639
TI  - Peritoneal Carcinosarcoma and Ovarian Papillary Serous Carcinoma Are the Same
      Origin: Analysis of TP53 Mutation and Microsatellite Suggests a Monoclonal
      Origin.

PMID- 25588640
TI  - Malignant perivascular epithelioid cell tumor of the uterus with lung metastasis.

PMID- 25588641
TI  - Lymphoepithelioma-like Carcinoma of the Renal Pelvis: A Case Report and Review of
      the Literature.

PMID- 25588642
TI  - Supratentorial hemangioblastoma with unusual features.

PMID- 25588643
TI  - A rare case of mesothelioma showing micropapillary and small cell differentiation
      with aggressive behavior.

PMID- 25588644
TI  - Going places: Does the two-minute walk test predict the six-minute walk test in
      lower extremity amputees?
AB  - OBJECTIVE: Assessing a patient's ability to walk the distance required for
      community ambulation (at least 300 m) is important in amputee rehabilitation.
      During the 2-min walk test, most amputees cannot walk 300 m. Thus, the 6-min walk
      test may be preferred, but it has not been fully validated in this population.
      This study examined the convergent and discriminative validity of the 6-min walk
      test and assessed whether the 2-min test could predict the results of the 6-min
      test. METHODS: A total of 86 patients with unilateral or bilateral amputations at
      the Syme, transtibial, knee disarticulation or transfemoral level completed the 6
      min walk test, 2-min walk test, Timed Up and Go test, Locomotor Capabilities
      Index version 5, Houghton Scale of Prosthetic Use, and Activity-Specific Balance
      Confidence scale. RESULTS: The 6-min walk test correlated with the other tests (R
      = 0.57-0.95), demonstrating convergent validity. It demonstrated discriminative
      validity with respect to age, aetiology of amputation, and K-level (p < 0.0001).
      The 2-min walk test was highly predictive of the 6-min walk test distance (R2 =
      0.91). CONCLUSION: The 6-min walk test is a valid measure of amputee ambulation.
      However, the results suggest that it may not be necessary, since the 2-min walk
      test strongly predicts the 6-min walk test. Clinicians could therefore save time
      by using the shorter test.

PMID- 25588645
TI  - Editorial.

PMID- 25588646
TI  - Medicare per capita spending by age and service: new data highlights oldest
      beneficiaries.

PMID- 25588647
TI  - Mesoporous alumina from colloidal biotemplating of Al clusters.
AB  - A simple and green synthesis route was disclosed for the achievement of
      mesoporous alumina microparticles employing polysaccharide nanoparticles (alpha
      chitin nanorods) as templates. Pore textures can be tuned by the cationic alumina
      precursor. Compared to small cations, the use of Al13 and Al30 oxo-hydroxo
      clusters leads to better defined and elongated mesopores. Electron microscopy and
      spectroscopic ((13) C, (27) Al NMR, XPS) measurements demonstrated that this is
      related to the effective coating of alpha-chitin nanorods by these pre-condensed
      colloids. 

PMID- 25588648
TI  - Identification of mutations in the HVR1 and PKR-BD regions in HCV-infected
      patients resistant to PEG-IFNalpha/RBV therapy.
AB  - The identification of mutations in the HVR1 region of hepatitis type C virus
      (HCV) is time-consuming and expensive, and there is a need for a rapid,
      inexpensive method of screening for these mutations to predict the
      ineffectiveness of pegylated interferon alpha combined with ribavirin (PEG
      IFNalpha/RBV) therapy. The project was designed to evaluate the usefulness of the
      high resolution melting (HRM) technique to screen for mutation in the cDNAs
      encoding the HVR1 and protein kinase R-binding domain (PKR-BD) regions in a group
      of 36 patients infected with HCV and resistant to 12 months of combined therapy
      with PEG-IFNalpha/RBV. Viral RNA was isolated, reverse transcribed, and the
      fragments encoding the HVR1 and PKR-BD regions were polymerase chain reaction
      (PCR)-amplified, cloned, sequenced, and the melting profiles and the melting
      temperature (Tm) were determined by the HRM technique. After the treatment, the
      melting profiles of HVR1 cDNAs revealed a dominant peak corresponding to the Tm
      of about 85  degrees C (HCVs85) in almost all patients. One or more minor peaks
      were also observed, indicating the existence of cDNA(s) of different Tm. The HMR
      analysis suggested four typical forms of response to treatment. These
      suppositions were supported by sequencing. The HRM analysis revealed no changes
      in the melting profiles of PKR-BD cDNAs in the same patient before and after the
      therapy, suggesting that, within 12 months of treatment, new mutations were not
      introduced in PKR-BD. These findings were substantiated by sequencing. The HRM
      technique can be applied for the rapid screening for mutations in the cDNAs
      encoding the HVR and PKR-BD regions of HCV. We suggest that the detection of
      HCVs85 peak before the IFNalpha/RBV therapy might predict the ineffectiveness of
      treatment.

PMID- 25588649
TI  - Genome-wide association study of antibody level response to NDV and IBV in
      Jinghai yellow chicken based on SLAF-seq technology.
AB  - Newcastle disease (ND) and avian infectious bronchitis (IB) are contagious
      diseases of chickens. To identify genes associated with antibody levels against
      ND and IB, a genome-wide association study was performed using specific-locus
      amplified fragment sequencing (SLAF-seq) technology in Jinghai yellow chickens.
      This determined six single-nucleotide polymorphisms (SNPs) that were associated
      with antibody levels against Newcastle disease virus (NDV): rsZ2494661,
      rsZ2494710, rs1211307701, rs1211307711, rs1218289310 and rs420701988. Of these,
      rsZ2494661 and rsZ2494710 reached the 5 % Bonferroni genome-wide significance
      level (5.5E-07) and they were both 134.7 kb downstream of the SETBP1 gene. The
      remaining four SNPs had 'suggestive' genome-wide significance levels (1.1E-05)
      and they were within or near the Plexin B1, LRRN1 and PDGFC genes. IB had two
      SNPs associated with antibody levels: rs149988433 and rs16170823; both reached
      chromosome-wide significance levels and they were near the USP7 and TRIM27 genes,
      respectively. Bioinformatics, GO annotation and pathway analysis indicated that
      five of these genes (Plexin B1, TRIM27, PDGFC, SETBP1 and USP7) may be important
      for the generation of protective antibodies against NDV and infectious bronchitis
      virus (IBV). This paves the way for further research on host immune responses
      against NDV.

PMID- 25588650
TI  - Contribution of the BacT/Alert MB Mycobacterium bottle to bloodstream infection
      surveillance in Thailand: added yield for Burkholderia pseudomallei.
AB  - Community-acquired bloodstream infections cause substantial morbidity and
      mortality worldwide, but microbiology capacity and surveillance limitations have
      challenged good descriptions of pathogen distribution in many regions, including
      Southeast Asia. Active surveillance for bloodstream infections has been conducted
      in two rural Thailand provinces for >7 years. Blood specimens were divided into
      two culture bottles, one optimized for aerobic growth (F bottle) and a second for
      enhanced growth of mycobacteria (MB bottle), and processed with the BactT/Alert
      3D system. Because the routine use of MB culture bottles is resource intensive
      (expensive and requires prolonged incubation), we assessed the added yield of MB
      bottles by comparing the proportion of pathogens detected by MB versus that by F
      bottles from 2005 to 2012. Of 63,066 blood cultures, 7,296 (12%) were positive
      for at least one pathogen; the most common pathogens were Escherichia coli (28%),
      Burkholderia pseudomallei (11%), Klebsiella pneumoniae (9%), and Staphylococcus
      aureus (6%). Two bottles improved the yield overall, but the added yield
      attributable to the MB bottles was limited to a few pathogens. In addition to the
      detection of mycobacteria and some fungi, MB bottles improved the detection of B.
      pseudomallei (27% [MB] versus 8% [F]; P < 0.0001), with added benefit if therapy
      was initiated prior to the blood culture. The targeted use of MB bottles is
      warranted for patients at risk for mycobacterial and fungal infections and for
      infection with B. pseudomallei, a common cause of septicemia in Thailand. 

PMID- 25588651
TI  - Evaluation of antigen-specific immunoglobulin g responses in pulmonary
      tuberculosis patients and contacts.
AB  - This study aimed to evaluate the serodiagnostic potential of immunoglobulin G
      (IgG) responses to Mycobacterium tuberculosis antigens in pulmonary tuberculosis
      (TB) patients, recent TB contacts with latent TB infection (LTBI), and healthy
      subjects. Infections were assessed using tuberculin skin tests, QuantiFERON-TB
      Gold In-Tube tests, drug susceptibility testing, and molecular genotyping of
      clinical isolates. Serum IgG responses to selective M. tuberculosis antigens,
      including the 38-kDa and 16-kDa antigens, lipoarabinomannan (LAM), and
      recombinant early secreted antigen target 6 kDa (ESAT-6) and culture filtrate
      protein 10 kDa (CFP-10), were determined. We found that the serum IgG responses
      to all antigens might differentiate between active TB and LTBI, with LAM having
      the highest diagnostic value (area under the curve [AUC] of 0.7756, P < 0.001).
      Recurrent TB cases showed significantly higher IgG responses to 38 kDa, CFP-10 (P
      < 0.01), and LAM (P < 0.05) than new cases, and male patients had higher levels
      of antigen-specific IgG than females (P < 0.05). Conversely, drug resistance and
      patient body mass index did not affect IgG responses (P > 0.05). LAM-specific IgG
      responses differentiated between acid-fast bacillus (AFB) smear-positive and 
      negative patients (P < 0.01), whereas antigen-specific IgG responses did not vary
      with the M. tuberculosis genotype (P > 0.05). Significantly higher IgG responses
      to 38 kDa and 16 kDa were observed in AFB smear-negative patients than in
      controls. These results suggest that assessment of serum IgG responses to
      selective purified M. tuberculosis antigens may help improve the diagnosis of
      active TB, particularly for sputum smear-negative patients or recurrent cases,
      and these may also help to differentiate between active TB and LTBI. 

PMID- 25588654
TI  - Development of a real-time PCR Assay for identification of Coccidioides immitis
      by use of the BD Max system.
AB  - Rapid real-time PCR (RT-PCR) can be performed in a community hospital setting to
      identify Coccidioides species using the new Becton Dickinson molecular instrument
      BD Max. Following sample preparation, DNA extraction and PCR were performed on
      the BD Max using the BD Max extraction kit ExK-DNA-1 test strip and a master mix
      prepared by BioGX (Birmingham, AL). Sample preparation took 2 h, and testing on
      the BD Max took an additional 2 h. Method sensitivity and specificity were
      evaluated along with the limits of detection to confirm that this convenient
      method would provide medically useful information. Using serial dilutions, the
      lower limit of detection was determined to be 1 CFU/MUl. Testing with this method
      was validated using samples from various body sites, including bronchial alveolar
      lavage (BAL) fluid; sputum and lung tissue samples; and pleural and spinal
      fluids. Safety protocols were established, and specimen preparation processes
      were developed for the various types of specimens. The range for the cycle
      threshold (CT) indicating adequate fluorescent signal to signify a positive
      result was established along with the acceptable range for the internal standard.
      Positive controls run with each batch were prepared by spiking a pooled BAL fluid
      specimen with a known dilution of Coccidioides immitis organism. Our experience
      with testing >330 patient samples shows that clinically relevant information can
      be available within 4 h using an RT-PCR method on the BD Max to identify
      Coccidioides spp., with sensitivity equivalent to culture. 

PMID- 25588652
TI  - Multicenter evaluation of the BioFire FilmArray gastrointestinal panel for
      etiologic diagnosis of infectious gastroenteritis.
AB  - The appropriate treatment and control of infectious gastroenteritis depend on the
      ability to rapidly detect the wide range of etiologic agents associated with the
      disease. Clinical laboratories currently utilize an array of different
      methodologies to test for bacterial, parasitic, and viral causes of
      gastroenteritis, a strategy that suffers from poor sensitivity, potentially long
      turnaround times, and complicated ordering practices and workflows. Additionally,
      there are limited or no testing methods routinely available for most
      diarrheagenic Escherichia coli strains, astroviruses, and sapoviruses. This study
      assessed the performance of the FilmArray Gastrointestinal (GI) Panel for the
      simultaneous detection of 22 different enteric pathogens directly from stool
      specimens: Campylobacter spp., Clostridium difficile (toxin A/B), Plesiomonas
      shigelloides, Salmonella spp., Vibrio spp., Vibrio cholerae, Yersinia
      enterocolitica, enteroaggregative E. coli, enteropathogenic E. coli,
      enterotoxigenic E. coli, Shiga-like toxin-producing E. coli (stx1 and stx2)
      (including specific detection of E. coli O157), Shigella spp./enteroinvasive E.
      coli, Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica,
      Giardia lamblia, adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A,
      and sapovirus. Prospectively collected stool specimens (n = 1,556) were evaluated
      using the BioFire FilmArray GI Panel and tested with conventional stool culture
      and molecular methods for comparison. The FilmArray GI Panel sensitivity was 100%
      for 12/22 targets and >=94.5% for an additional 7/22 targets. For the remaining
      three targets, sensitivity could not be calculated due to the low prevalences in
      this study. The FilmArray GI Panel specificity was >=97.1% for all panel targets.
      The FilmArray GI Panel provides a comprehensive, rapid, and streamlined
      alternative to conventional methods for the etiologic diagnosis of infectious
      gastroenteritis in the laboratory setting. The potential advantages include
      improved performance parameters, a more extensive menu of pathogens, and a
      turnaround time of as short as 1 h. 

PMID- 25588653
TI  - Development and validation of a quantitative PCR assay using multiplexed
      hydrolysis probes for detection and quantification of Theileria orientalis
      isolates and differentiation of clinically relevant subtypes.
AB  - Theileria orientalis is an emerging pathogen of cattle in Asia, Australia, and
      New Zealand. This organism is a vector-borne hemoprotozoan that causes clinical
      disease characterized by anemia, abortion, and death, as well as persistent
      subclinical infections. Molecular methods of diagnosis are preferred due to their
      sensitivity and utility in differentiating between pathogenic and apathogenic
      genotypes. Conventional PCR (cPCR) assays for T. orientalis detection and typing
      are laborious and do not provide an estimate of parasite load. Current real-time
      PCR assays cannot differentiate between clinically relevant and benign genotypes
      or are only semiquantitative without a defined clinical threshold. Here, we
      developed and validated a hydrolysis probe quantitative PCR (qPCR) assay which
      universally detects and quantifies T. orientalis and identifies the clinically
      associated Ikeda and Chitose genotypes (UIC assay). Comparison of the UIC assay
      results with previously validated universal and genotype-specific cPCR results
      demonstrated that qPCR detects and differentiates T. orientalis with high
      sensitivity and specificiy. Comparison of quantitative results based on percent
      parasitemia, determined via blood film analysis and packed cell volume (PCV)
      revealed significant positive and negative correlations, respectively. One-way
      analysis of variance (ANOVA) indicated that blood samples from animals with
      clinical signs of disease contained statistically higher concentrations of T.
      orientalis DNA than animals with subclinical infections. We propose clinical
      thresholds to assist in classifying high-, moderate-, and low-level infections
      and describe how parasite load and the presence of the Ikeda and Chitose
      genotypes relate to disease. 

PMID- 25588655
TI  - Defining the phylogenomics of Shigella species: a pathway to diagnostics.
AB  - Shigellae cause significant diarrheal disease and mortality in humans, as there
      are approximately 163 million episodes of shigellosis and 1.1 million deaths
      annually. While significant strides have been made in the understanding of the
      pathogenesis, few studies on the genomic content of the Shigella species have
      been completed. The goal of this study was to characterize the genomic diversity
      of Shigella species through sequencing of 55 isolates representing members of
      each of the four Shigella species: S. flexneri, S. sonnei, S. boydii, and S.
      dysenteriae. Phylogeny inferred from 336 available Shigella and Escherichia coli
      genomes defined exclusive clades of Shigella; conserved genomic markers that can
      identify each clade were then identified. PCR assays were developed for each
      clade-specific marker, which was combined with an amplicon for the conserved
      Shigella invasion antigen, IpaH3, into a multiplex PCR assay. This assay
      demonstrated high specificity, correctly identifying 218 of 221 presumptive
      Shigella isolates, and sensitivity, by not identifying any of 151 diverse E. coli
      isolates incorrectly as Shigella. This new phylogenomics-based PCR assay
      represents a valuable tool for rapid typing of uncharacterized Shigella isolates
      and provides a framework that can be utilized for the identification of novel
      genomic markers from genomic data. 

PMID- 25588656
TI  - Evaluation of enzyme immunoassays and real-time PCR for detecting Shiga toxin
      producing Escherichia coli in Southern Alberta, Canada.
AB  - Two immunoassays (Shiga Toxin Chek and Shiga Toxin Quik Chek) and real-time PCR
      were used to detect Shiga toxin-producing Escherichia coli. For enriched culture,
      the sensitivity and specificity of the three methods ranged from 80.0% to 98.2%
      and 98.0% to 100.0%, respectively. STEC isolates were identified in 2.6% of the
      784 samples. 

PMID- 25588657
TI  - Characterization of enterovirus activity, including that of enterovirus D68, in
      pediatric patients in Alberta, Canada, in 2014.

PMID- 25588658
TI  - Detection of a transient R292K mutation in influenza A/H3N2 viruses shed for
      several weeks by an immunocompromised patient.
AB  - We describe the case of an immunocompromised patient, positive for influenza A
      virus (H3N2), in whom the neuraminidase R292K mutation was transiently detected
      during oseltamivir treatment. The R292K mutation was identified by direct testing
      in 3 of 11 respiratory specimens collected throughout the patient's illness but
      in none of the cultures from those specimens. 

PMID- 25588660
TI  - Detection of mycobacteria, Mycobacterium avium subspecies, and Mycobacterium
      tuberculosis complex by a novel tetraplex real-time PCR assay.
AB  - Mycobacterium tuberculosis complex, Mycobacterium avium, and many other
      nontuberculous mycobacteria are worldwide distributed microorganisms of major
      medical and veterinary importance. Considering the growing epidemiologic
      significance of wildlife-livestock-human interrelation, developing rapid
      detection tools of high specificity and sensitivity is vital to assess their
      presence and accelerate the process of diagnosing mycobacteriosis. Here we
      describe the development and evaluation of a novel tetraplex real-time PCR for
      simultaneous detection of Mycobacterium genus, M. avium subspecies, and M.
      tuberculosis complex in an internally monitored single assay. The method was
      evaluated using DNA from mycobacterial (n = 38) and nonmycobacterial (n = 28)
      strains, tissues spiked with different CFU amounts of three mycobacterial species
      (n = 57), archival clinical samples (n = 233), and strains isolated from various
      hosts (n = 147). The minimum detectable DNA amount per reaction was 50 fg for M.
      bovis BCG and M. kansasii and 5 fg for M. avium subsp. hominissuis. When spiked
      samples were analyzed, the method consistently detected as few as 100 to 1,000
      mycobacterial CFU per gram. The sensitivity and specificity values for the panel
      of clinical samples were 97.5 and 100% using a verified culture-based method as
      the reference method. The assays performed on clinical isolates confirmed these
      results. This PCR was able to identify M. avium and M. tuberculosis complex in
      the same sample in one reaction. In conclusion, the tetraplex real-time PCR we
      designed represents a highly specific and sensitive tool for the detection and
      identification of mycobacteria in routine laboratory diagnosis with potential
      additional uses. 

PMID- 25588662
TI  - Do turtles follow the rules? Latitudinal gradients in species richness, body
      size, and geographic range area of the world's turtles.
AB  - Understanding how and why biodiversity is structured across the globe has been
      central to ecology, evolution, and biogeography even before those disciplines
      took their modern forms. Three global-scale patterns in particular have been the
      focus of research and debate for decades: latitudinal gradients in species
      richness (richness decreases with increasing latitude), body size (body size
      increases with increasing latitude in endotherms; Bergmann's rule), and
      geographic range size (range size increases with increasing latitude; Rapoport's
      rule). Despite decades of study, the generality and robustness of these trends
      have been debated, as have their underlying causes. Here we investigate
      latitudinal gradients in species richness, body size, and range size in the
      world's turtles (Testudines), and add more evidence that these rules do not seem
      to apply across all taxa. We show that turtle diversity actually peaks at 25
      degrees  north, a highly unusual global pattern. Turtles also fail to follow
      Bergmann's Rule, and may show the converse (larger at lower latitudes), though
      trends are weak. Turtles also show a complex relationship between latitude and
      range size that does not directly follow Rapoport's rule. Body size and
      geographic range size are significantly correlated, and multiple abiotic and
      biotic variables help explain the relationships between latitude and species
      diversity, body size, and range size. Although we show that turtles do not
      strictly follow some classic biogeographical rules, we also call for further in
      depth research to investigate potential causal mechanisms for these atypical
      patterns.

PMID- 25588661
TI  - Twist1 and Snail link Hedgehog signaling to tumor-initiating cell-like properties
      and acquired chemoresistance independently of ABC transporters.
AB  - The Hedgehog (Hh) signaling pathway has been implicated in acquired
      chemoresistance. However, it remains unclear whether and how the Hh pathway may
      maintain the chemoresistant phenotype by controlling the tumor-initiating cell
      like properties of acquired chemoresistant cancer cells. In this study, using
      well-established acquired chemoresistant cancer cells and chemosensitive KB
      cancer cells with artificially elevated Hh pathway activity, we found that Hh
      pathway activity may transcriptionally control the expression of twist1 and
      snail, thereby maintaining the tumor-initiating cell-like properties and
      consequently the chemoresistant phenotype. Meanwhile, we obtained direct evidence
      that twist1, which may amplify Hh signaling activity and plays an essential role
      in limb development, is a direct transcriptional target of Gli, similar to snail.
      We further observed that the expression of ATP-binding cassette (ABC)
      transporters was dispensable for the chemoresistance mediated by twist1 and
      snail. Collectively, these findings demonstrate that twist1, together with snail,
      links the Hh pathway to the tumor-initiating cell-like properties of
      chemoresistant cells. This consequently promotes chemoresistance independently of
      ABC transporters, thereby contributing to future development of strategies for
      combating chemoresistance through Hh pathway interference. Furthermore, our
      finding that twist1 is a direct target of the transcription factor Gli improves
      the interpretation of the association between twist1 and the Hh pathway and the
      nature of the signaling transduction of the Hh pathway.

PMID- 25588659
TI  - Multicountry prospective clinical evaluation of two enzyme-linked immunosorbent
      assays and two rapid diagnostic tests for diagnosing dengue fever.
AB  - We evaluated four dengue diagnostic devices from Alere, including the SD Bioline
      Dengue Duo (nonstructural [NS] 1 Ag and IgG/IgM), the Panbio Dengue Duo Cassette
      (IgM/IgG) rapid diagnostic tests (RDTs), and the Panbio dengue IgM and IgG
      capture enzyme-linked immunosorbent assays (ELISAs) in a prospective, controlled,
      multicenter study in Peru, Venezuela, Cambodia, and the United States, using
      samples from 1,021 febrile individuals. Archived, well-characterized samples from
      an additional 135 febrile individuals from Thailand were also used. Reference
      testing was performed on all samples using an algorithm involving virus
      isolation, in-house IgM and IgG capture ELISAs, and plaque reduction
      neutralization tests (PRNT) to determine the infection status of the individual.
      The primary endpoints were the clinical sensitivities and specificities of these
      devices. The SD Bioline Dengue Duo had an overall sensitivity of 87.3% (95%
      confidence interval [CI], 84.1 to 90.2%) and specificity of 86.8% (95% CI, 83.9
      to 89.3%) during the first 14 days post-symptom onset (p.s.o.). The Panbio Dengue
      Duo Cassette demonstrated a sensitivity of 92.1% (87.8 to 95.2%) and specificity
      of 62.2% (54.5 to 69.5%) during days 4 to 14 p.s.o. The Panbio IgM capture ELISA
      had a sensitivity of 87.6% (82.7 to 91.4%) and specificity of 88.1% (82.2 to
      92.6%) during days 4 to 14 p.s.o. Finally, the Panbio IgG capture ELISA had a
      sensitivity of 69.6% (62.1 to 76.4%) and a specificity of 88.4% (82.6 to 92.8%)
      during days 4 to 14 p.s.o. for identification of secondary dengue infections.
      This multicountry prospective study resulted in reliable real-world performance
      data that will facilitate data-driven laboratory test choices for managing
      patient care during dengue outbreaks. 

PMID- 25588663
TI  - Modified dorsal percutaneous screw fixation through a transtrapezial approach for
      scaphoid fractures.

PMID- 25588664
TI  - Arm versus forearm tourniquet for carpal tunnel decompression - Which is better?
      A randomized controlled trial.
AB  - Tourniquet pain is a common source of complaint for patients undergoing carpal
      tunnel decompression and practice varies as to the tourniquet position used.
      There is little evidence to suggest benefit of one position over another. Our aim
      was to compare patient and surgeon experience of forearm and arm tourniquets.
      Following a power calculation, 100 patients undergoing open carpal tunnel
      decompression under local anaesthetic were randomized to either an arm or a
      forearm tourniquet. Measurements of blood pressure, heart rate and pain were
      taken at 2.5 min intervals. The operating surgeon also provided a visual analogue
      scale rating for the extent of bloodless field achieved and for any obstruction
      caused by the tourniquet. There was no statistically significant inter-group
      difference in patient pain or physiological response, tourniquet time, bloodless
      field or length of procedure. The degree of obstruction caused by the tourniquet
      was significantly higher in the forearm group. LEVEL OF EVIDENCE: I. Prospective
      Randomized Controlled Trial.

PMID- 25588665
TI  - Subperiosteal ganglion cyst in distal end radius in an adolescent.

PMID- 25588666
TI  - Surgical adhesive BioGlueTM does not benefit tendon repair strength: an ex vivo
      study.
AB  - Surgical adhesives are useful supplements in surgery, but their benefit in tendon
      repair is uncertain. The purpose of this study was to evaluate the effect of
      BioGlueTM on strength of flexor tendon repair. A total of 60 porcine flexor
      tendons were divided into three groups. In group one, a conventional core and
      peripheral suture repair was used. In group two, a core suture and BioGlueTM were
      used. In group three, a conventional core and peripheral suture repair and
      BioGlueTM were used. We performed static and cyclic axial load testing and
      measured diameter of the repair site. We found that BioGlueTM did not improve the
      tensile strength when added to a core and peripheral suture and that there was an
      increase in bulk at the repair site. We conclude that BioGlueTM application
      cannot replace a peripheral suture as tensile strength significantly decreases
      without a peripheral suture, and it does not benefit a tendon already repaired
      with a core and peripheral suture. LEVEL OF EVIDENCE: n/a.

PMID- 25588667
TI  - Crowdfunding: from startup businesses to startup science.

PMID- 25588668
TI  - Osteometric sorting of skeletal elements from a sample of modern Colombians: a
      pilot study.
AB  - The Colombian armed conflict has been catalogued not only as the longest civil
      war in the western hemisphere, but also as having one of the highest indexes of
      missing persons. Among the several challenges faced by forensic practitioners in
      Colombia, the commingling of human remains has been recognised as one of the most
      difficult to approach. The method of osteometric sorting described by Byrd and
      Adams and Byrd (2008) has proven relevant as a powerful tool to aid in the
      reassociation process of skeletal structures. The aim of this research was to
      evaluate the three osteometric sorting models developed by Byrd (2008) (paired
      elements, articulating bone portions and other bone portions) in a sample of
      modern Colombian individuals. A set of 39 linear measurements was recorded from a
      sample of 100 individuals (47 females and 53 males aged between 20 and 74 and 18
      and 77 years, respectively), which was used to create a reference sample
      database. A different subset of eight individuals (five females aged between 23
      and 48 years, and three males aged between 27 and 43 years) was employed to
      randomly create six small-scale commingled assemblages for the purposes of
      testing the osteometric sorting models. Results demonstrate that this method has
      significant potential for use in the Colombian forensic context.

PMID- 25588669
TI  - Comment on "major source of error when calculating bone mechanical properties".

PMID- 25588670
TI  - A poroviscohyperelastic model for numerical analysis of mechanical behavior of
      single chondrocyte.
AB  - The aim of this paper is to use a poroviscohyperelastic (PVHE) model, which is
      developed based on the porohyperelastic (PHE) model to explore the mechanical
      deformation properties of single chondrocytes. Both creep and relaxation
      responses are investigated by using finite element analysis models of
      micropipette aspiration and atomic force microscopy experiments, respectively.
      The newly developed PVHE model is compared thoroughly with the standard neo
      Hookean solid and PHE models. It has been found that the PVHE can accurately
      capture both creep and stress relaxation behaviors of chondrocytes better than
      other two models. Hence, the PVHE is a promising model to investigate mechanical
      properties of single chondrocytes. 

PMID- 25588673
TI  - The toxicity of carbofuran to the freshwater rotifer, Philodina roseola.
AB  - In this study, the effects of exposing the rotifer Philodina roseola to the
      pesticide carbofuran were investigated. Its range of sensitivity to potassium
      dichromate, the acute toxicity of active ingredient carbofuran and of carbofuran
      dosed as its commercial form, Furadan((r)) 350 SC were determined. Chronic
      toxicity of carbofuran dosed as Furadan((r)) 350 SC on P. roseola survival and
      fecundity were also studied. The sensitivity of P. roseola to K2Cr2O7 ranged from
      29.52 to 64.67 mg L(-1), averaging 47.10 mg L(-1). The 48-h EC50 were 13.36 +/-
      2.63 mg L(-1) for carbofuran and 89.32 +/- 6.52 mg L(-1) for commercial form.
      Chronic toxicity tests showed that the survival of this rotifer was not affected
      by the carbofuran dosed as Furadan((r)) 350 SC at the concentrations tested and
      that at 1.56 and 3.12 mg L(-1) their fecundity was higher than in the absence of
      this commercial product, characterizing the hormesis phenomenon. The sensitivity
      profile of several species to carbofuran indicated that P. roseola is more
      susceptible to this pesticide than the fish Clarias batrachus, the bacterium
      Vibrio fischeri, the protozoan Paramecium caudatum and the rotifer Brachionus
      calyciflorus, although the acute toxicity of carbofuran dosed as Furadan((r)) 350
      SC to P. roseola is much lower than that of active ingredient carbofuran. The
      results also imply that the exacerbated use of pesticides and the constant,
      accelerated expansion of agricultural activity will make aquatic non-target
      species even more vulnerable. Furthermore, the relevant role of benthic organisms
      in aquatic environments justifies the inclusion of P. roseola and other benthic
      species in toxicity screening for risk assessment, regarding this environmental
      compartment. 

PMID- 25588675
TI  - Yellowing of desflurane in the vaporizer.

PMID- 25588674
TI  - Effects of tetracycline on developmental toxicity and molecular responses in
      zebrafish (Danio rerio) embryos.
AB  - The extensive use of pharmaceuticals has resulted in the intensive contamination
      of water bodies. Tetracycline is a type of antibiotic and its potential toxicity
      is causing environmental concern. The effects of developmental toxicity and the
      mechanisms of tetracycline on fish embryos are not well understood. Zebrafish
      embryos are used in this study to investigate the developmental toxicity of this
      compound. Four hour post-fertilization (hpf) zebrafish embryos are exposed to
      different concentrations of tetracycline until 96 hpf. The larvae display
      developmental delay phenotypes, including hatching delay, shorter body length,
      increased yolk sac area and uninflated swim bladder upon exposure to
      tetracycline. Delayed yolk sac absorption and swim bladder deficiency at 96 hpf
      are observed in the zebrafish larvae upon exposure to 20 MUg/L of tetracycline.
      To test whether tetracycline causes oxidative damage and the resulting oxidative
      stress-induced apoptosis, the generation of reactive oxygen species (ROS),
      Acridine Orange staining and real time polymerase chain reaction have been
      performed in this study. The results indicate that tetracycline exposure results
      in significant increases in ROS production and cell apoptosis, mainly in the tail
      areas at 96 hpf. The gene expression pattern demonstrates that tetracycline
      induces ROS which causes apoptosis in the zebrafish larvae, and the results also
      indicate that caspase-dependent apoptotic pathways may greatly contribute to
      tetracycline-induced apoptosis in the early-life stages of the zebrafish. In
      addition, we have investigated the effects of tetracycline on marker genes
      related to resistance mechanisms and gene regulating drug biotransformation. The
      results of these gene expression studies indicate that tetracycline could induce
      zebrafish to resist pharmaceuticals and Cytochrome P450s that are involved in the
      biotransformation of tetracycline in zebrafish larvae. The overall results
      indicate that tetracycline can produce oxidative stress and induce apoptosis,
      which brings about significant developmental delay in zebrafish embryos. 

PMID- 25588676
TI  - Differential regulation of hsp70 genes in the freshwater key species Gammarus
      pulex (Crustacea, Amphipoda) exposed to thermal stress: effects of latitude and
      ontogeny.
AB  - Temperature is one of the main abiotic factors influencing the distribution and
      abundance of organisms. In the Rhone River Valley, populations of the crustacean
      Gammarus pulex are distributed along a 5  degrees C thermal gradient from the
      North to the South of the valley. In this present work, we investigated the heat
      shock response of G. pulex according to latitudinal distribution (northern vs.
      southern populations) and ontogeny (adults vs. embryos from early stages). We
      isolated two isoforms (one constitutive hsc70 and one inducible hsp70) of heat
      shock proteins 70 (HSP70) and quantitatively compared their amounts of mRNA after
      heat shocks, using real-time PCR. Whereas the hsc70 (constitutive) gene did not
      vary between the two populations, a significant effect of the population was
      observed on the expression of the hsp70 (inducible) gene in adult specimens. The
      northern population of amphipods showed a greater magnitude of induction and a 2 
      degrees C lower onset temperature when compared to the southern population,
      suggesting that the northern population is more affected by elevated temperature
      than the southern one. We demonstrated that the expression of hsp70 may play a
      crucial role in the persistence of biogeographical patterns of G. pulex, since it
      reflects the natural distribution of this species along the latitudinal thermal
      gradient. A differential regulation of hsc70 gene was also observed according to
      the ontogenetic stage, with a switch from heat inducible in early life stages to
      constitutively and highly expressed in adults. These findings demonstrate the
      importance of considering the entire life cycle to better understand the adaptive
      response to thermal stress. 

PMID- 25588678
TI  - The future of MCH nutrition services: a commentary on the importance of
      supporting leadership training to strengthen the nutrition workforce.

PMID- 25588677
TI  - Platelet transfusions in platelet consumptive disorders are associated with
      arterial thrombosis and in-hospital mortality.
AB  - While platelets are primary mediators of hemostasis, there is emerging evidence
      to show that they may also mediate pathologic thrombogenesis. Little data are
      available on risks and benefits associated with platelet transfusions in
      thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia (HIT)
      and immune thrombocytopenic purpura (ITP). This study utilized the Nationwide
      Inpatient Sample to evaluate the current in-hospital platelet transfusion
      practices and their association with arterial/venous thrombosis, acute myocardial
      infarction (AMI), stroke, and in-hospital mortality over 5 years (2007-2011). Age
      and gender-adjusted odds ratios (adjOR) associated with platelet transfusions
      were calculated. There were 10 624 hospitalizations with TTP; 6332 with HIT and
      79 980 with ITP. Platelet transfusions were reported in 10.1% TTP, 7.1% HIT, and
      25.8% ITP admissions. Platelet transfusions in TTP were associated with higher
      odds of arterial thrombosis (adjOR = 5.8, 95%CI = 1.3-26.6), AMI (adjOR = 2.0,
      95%CI = 1.2-3.3) and mortality (adjOR = 2.0,95%CI = 1.3-3.0), but not venous
      thrombosis. Platelet transfusions in HIT were associated with higher odds of
      arterial thrombosis (adjOR = 3.4, 95%CI = 1.2-9.5) and mortality (adjOR = 5.2,
      95%CI = 2.6-10.5) but not venous thrombosis. Except for AMI, all relationships
      remained significant after adjusting for clinical severity and acuity. No
      associations were significant for ITP. Platelet transfusions are associated with
      higher odds of arterial thrombosis and mortality among TTP and HIT patients. 

PMID- 25588679
TI  - Mixed transcortical aphasia: a case report.

PMID- 25588680
TI  - Neural correlates of consciousness: what we know and what we have to learn!
AB  - Consciousness is a multifaceted concept with two major components: awareness of
      environment and of self (i.e., the content of consciousness) and wakefulness
      (i.e., the level of consciousness). Medically speaking, consciousness is the
      state of the patient's awareness of self and environment and his responsiveness
      to external stimulation and inner need. A basic understanding of consciousness
      and its neural correlates is of major importance for all clinicians, especially
      those involved with patients suffering from altered states of consciousness. To
      this end, in this review it is shown that consciousness is dependent on the
      brainstem and thalamus for arousal; that basic cognition is supported by
      recurrent electrical activity between the cortex and the thalamus at gamma band
      frequencies; and that some kind of working memory must, at least fleetingly, be
      present for awareness to occur. New advances in neuroimaging studies are also
      presented in order to better understand and demonstrate the neurophysiological
      basis of consciousness. In particular, recent functional magnetic resonance
      imaging studies have offered the possibility to measure directly and non
      invasively normal and severely brain damaged subjects' brain activity, whilst
      diffusion tensor imaging studies have allowed evaluating white matter integrity
      in normal subjects and patients with disorder of consciousness. 

PMID- 25588682
TI  - A novel experimental study on the fabrication and biological characteristics of
      canine bone marrow mesenchymal stem cells sheet using vitamin C.
AB  - The aim of this study was to fabricate canine bone marrow mesenchymal stem cell
      sheet through the use of vitamin C, to identify the biological characteristics of
      the resulting cell sheets, and to reveal the potential mechanism of cell-sheet
      promotion by vitamin C. This study used vitamin C to induce bone marrow
      mesenchymal stem cells to proliferate. The resulting cells secreted large amounts
      of collagen, thereby shortening the construction time of the cell-sheet layer. In
      addition to these aims, we identified biological microcharacteristics of the cell
      sheet through histological observation, transmission electron microscopy, real
      time PCR detection, immunohistochemical detection, and osteogenesis-induction
      experiments on the cell sheet. We were able to stably and rapidly construct bone
      marrow mesenchymal stem cell sheet, effectively harvest it, and transfer the seed
      cells for tissue engineering. This study indicates that the use of vitamin C for
      harvesting mesenchymal stem cell sheets from bone marrow may provide an easy and
      practical approach for bone tissue regeneration.

PMID- 25588681
TI  - A case of type B lactic acidosis as a complication of chronic myelomonocytic
      leukaemia: a case report and review of the literature.
AB  - INTRODUCTION: Type B lactic acidosis represents a rare and often lethal
      complication of haematological malignancy. Here, we present a patient who
      developed a type B lactic acidosis presumably due to a concurrent chronic
      myelomonocytic leukaemia. Upon swift initiation of cytoreductive chemotherapy
      (doxorubicin), the lactic acidosis was rapidly brought under control. This case
      adds to the literature reporting other haematological malignancies that can cause
      a type B lactic acidosis and its successful treatment. CASE PRESENTATION: We
      report the case of a 77-year-old Caucasian man brought to our Accident and
      Emergency department following an unwitnessed collapse; he was found surrounded
      by coffee-ground vomit. Although haemodynamically stable on admission, he rapidly
      deteriorated as his lactic acid rose. An initial arterial blood gas revealed a pH
      of 7.27 and lactate of 18mmol/L (peaking at 21mmol/L). CONCLUSIONS: A high degree
      of clinical suspicion for haematological malignancy should be held when presented
      with a patient with lactic acidosis in clinical practice, even without evidence
      of poor oxygenation or another cause. Treatment with emergency chemotherapy, in
      lieu of a definitive diagnosis, was rapidly successful at lowering lactate levels
      within 8 hours. This may suggest a causal and perhaps direct relationship between
      lactic acid production and the presence of leukemic cells. Veno-venous
      haemofiltration had no apparent effect on reducing the lactic acidosis and
      therefore its benefit is questioned in this setting, especially at the cost of
      delaying chemotherapy. In the face of a life-threatening lactic acidosis,
      pragmatic clinical judgement alone may justify the rapid initiation of
      chemotherapy.

PMID- 25588683
TI  - Tissue engineering and regenerative medicine in applied research: a year in
      review of 2014.
AB  - Tissue engineering and regenerative medicine (TERM) remains to be one of the
      fastest growing fields, which covers a wide scope of topics of both basic and
      applied biological researches. This overview article summarized the advancements
      in applied researches of TERM area, including stem cell-mediated tissue
      regeneration, material science, and TERM clinical trial. These achievements
      demonstrated the great potential of clinical regenerative therapy of tissue/organ
      disease or defect through stem cells and tissue engineering approaches. 

PMID- 25588685
TI  - A novel marker to predict early recurrence after atrial fibrillation ablation:
      the ablation effectiveness quotient.
AB  - INTRODUCTION: Inability to predict clinical outcome despite acutely successful
      pulmonary vein isolation (PVI) remains the Achilles' heel of atrial fibrillation
      ablation (AFA). Arrhythmia recurrence is frequently due to recovery of
      radiofrequency (RF) ablation lesions believed to be complete at the original
      procedure. OBJECTIVES: We hypothesized that a high ratio between post-AFA levels
      of serum high sensitivity cardiac troponin T (HScTnT), a highly specific marker
      of acute myocardial injury, and duration of RF application (the ablation
      effectiveness quotient, AEQ) would indicate effective ablation and correlate with
      early clinical success. METHODS: We prospectively measured HScTnT levels in 60
      patients (42 [70%] male, 22 [37%] with paroxysmal AF [PAF], mean age 62.5 +/-
      10.6 years) 12-18 hours after AFA and calculated the AEQ for each. Patients were
      followed-up with ECGs and Holter monitors for recurrence of atrial
      tachyarrhythmia (AT). RESULTS: Early recurrence of AT within 6 months occurred in
      22 (37%). AT recurrence was not significantly related to left atrial size or
      comorbidities, nor to RF time or HScTnT level. Mean AEQ was significantly lower
      in those with recurrence than those without (0.35 +/- 0.14 ng/L/s vs. 0.45 +/-
      0.18 ng/L/s), P = 0.02. Subgroup analysis showed this finding was due to patients
      with PAF in whom early significance was maintained to one year, with an AEQ >0.4
      ng/L/s having 75% sensitivity and 90% specificity in predicting freedom from AT.
      CONCLUSION: A high AEQ correlates well with freedom from AT in patients with PAF
      in both the short and medium term. If confirmed in further studies, AEQ may
      become a useful marker of risk of AT post-AFA.

PMID- 25588686
TI  - Toxic Epidermal Necrolysis During Dronedarone Treatment: First Report of a Severe
      Serious Adverse Event Of A New Antiarrhythmic Drug.
AB  - A 77-year-old female patient with symptomatic atrial fibrillation with fast
      ventricular rate despite conventional antiarrhythmic therapy was treated with
      dronedarone. Five days later, she developed a maculopapulous exanthema and small
      flaccid blisters, which spread over the common integument predominantly located
      on the dorsal trunk. Over few days, the patient showed a severe epidermal
      necrolysis of approximately 30 % of the body area and ultimately died in
      multiorgan failure. Here, we report a rare case of toxic epidermal necrolysis
      during treatment with dronedarone leading to patient death. 

PMID- 25588688
TI  - Health literacy, vulnerable patients, and health information technology use:
      where do we go from here?

PMID- 25588687
TI  - The Natural Antimicrobial Subtilosin A Synergizes with Lauramide Arginine Ethyl
      Ester (LAE), epsilon-Poly-L-lysine (Polylysine), Clindamycin Phosphate and
      Metronidazole, Against the Vaginal Pathogen Gardnerella vaginalis.
AB  - Bacterial vaginosis (BV) is a common, recurrent vaginal infection linked to
      increased chances of preterm delivery, incidence of sexually transmitted
      infections and fertility problems. BV is caused by a shift of the vaginal
      ecosystem from predominately Lactobacillus to a multispecies Actinomyces biofilm
      with the most common representatives identified as Gardnerella vaginalis and
      Prevotella spp. Current treatments have been associated with increased resistance
      as well as negative effects on healthy microbiota. The objective of this study
      was to evaluate the synergistic potential of ten two-antimicrobial combinations
      against G. vaginalis and four representative lactobacilli. The four tested
      antimicrobials were lauramide arginine ethyl ester, epsilon-poly-L-lysine,
      clindamycin phosphate, metronidazole and the bacteriocin subtilosin A. The use of
      bacteriocins as either synergist or alternative treatment positions bacteriocins
      as an excellent alternative to current antibiotics. The microdilution method was
      used to determine the minimum inhibitory concentration (MIC) of each of the
      antimicrobials individually, and the checkerboard assay was used to evaluate
      these MICs in combination. Clindamycin and subtilosin (CS), and metronidazole and
      subtilosin were synergistic against G. vaginalis in terms of fractional
      inhibitory concentration index (FICI). All tested combinations were found to have
      Bliss synergy. The combination of clindamycin and polylysine (CP) was identified
      as antagonistic against L. acidophilus in terms of both FICI and Bliss synergy.
      The combination of clindamycin and metronidazole (CM) was antagonistic against L.
      vaginalis for both FICI and Bliss synergy. The combinations of CP, clindamycin
      and LAE, CS, and LAE and polylysine were identified as Bliss antagonistic against
      L. vaginalis but did not indicate FICI antagonism. 

PMID- 25588689
TI  - Control of selectivity in allylic alcohol oxidation on gold surfaces: the role of
      oxygen adatoms and hydroxyl species.
AB  - Gold catalysts display high activity and good selectivity for partial oxidation
      of a number of alcohol species. In this work, we discuss the effects of oxygen
      adatoms and surface hydroxyls on the selectivity for oxidation of allylic
      alcohols (allyl alcohol and crotyl alcohol) on gold surfaces. Utilizing
      temperature programmed desorption (TPD), reactive molecular beam scattering
      (RMBS), and density functional theory (DFT) techniques, we provide evidence to
      suggest that the selectivity displayed towards partial oxidation versus
      combustion pathways is dependent on the type of oxidant species present on the
      gold surface. TPD and RMBS results suggest that surface hydroxyls promote partial
      oxidation of allylic alcohols to their corresponding aldehydes with very high
      selectivity, while oxygen adatoms promote both partial oxidation and combustion
      pathways. DFT calculations indicate that oxygen adatoms can react with acrolein
      to promote the formation of a bidentate surface intermediate, similar to
      structures that have been shown to decompose to generate combustion products over
      other transition metal surfaces. Surface hydroxyls do not readily promote such a
      process. Our results help explain phenomena observed in previous studies and may
      prove useful in the design of future catalysts for partial oxidation of alcohols.

PMID- 25588690
TI  - Right anterior mini-thoracotomy direct aortic self-expanding trans-catheter
      aortic valve implantation: A single center experience.
AB  - OBJECTIVE: Transcatheter aortic valve implantation (TAVI) has been designed to
      treat elderly patients with severe aortic stenosis at high risk for surgery.
      These patients are also often affected by severe iliac-femoral arteriopathy,
      rendering the trans-femoral approach unusable. We report our experience with the
      direct-aortic approach to treat these patients. METHODS: From May 2008 to
      November 2013 two hundred and thirty-two patients (131 female, 56%) with severe
      symptomatic aortic stenosis and no reasonable surgical option due to excessive
      risk were evaluated for TAVI at our department. Of these patients, 202 were
      deemed eligible for TAVI. Of this group, 50 underwent CoreValve implantation by
      the direct aortic approach through a right anterior mini-thoracotmy (28 female,
      56%), mean age 81.2+/-6.9. A combined team of cardiologists, cardiac surgeons
      with expertise in hybrid procedures, and anesthetists performed all the
      procedures. RESULTS: Twenty-eight (56%) patients were female and 11 (22%) were
      redo at TAVI. We used a 23-mm CoreValve Evolute in 3 patients (6%), and the most
      used valve size was the 29mm in 46% of patients. Mean hemodynamic trans-aortic
      gradient was less than 5mmHg. The paravalvular regurgitation was <= grade 1 in 46
      patients as assessed by peri-procedural transesophageal echocardiography (TEE).
      Seven patients (7/43, 16%) required a permanent pacemaker implantation; 30-day
      mortality was 6% (3 patients). Seven patients (14.8%) died during follow-up.
      Actuarial survival at 2years is 84.7+/-5.3%. CONCLUSIONS: Transcatheter aortic
      valve implantation with the direct aortic approach is safe and feasible, offering
      a new attractive option to treat selected high-risk patients with severe aortic
      stenosis and peripheral vasculopathy, including those requiring a re-do
      procedure.

PMID- 25588691
TI  - Access to Investigational Drugs: FDA Expanded Access Programs or "Right-to-Try"
      Legislation?
AB  - PURPOSE: The Food and Drug Administration Expanded Access (EA) program and "Right
      to-Try" legislation aim to provide seriously ill patients who have no other
      comparable treatment options to gain access to investigational drugs and
      biological agents. Physicians and institutions need to understand these programs
      to respond to questions and requests for access. METHODS: FDA EA programs and
      state and federal legislative efforts to provide investigational products to
      patients by circumventing FDA regulations were summarized and compared. RESULTS:
      The FDA EA program includes Single Patient-Investigational New Drug (SP-IND),
      Emergency SP-IND, Intermediate Sized Population IND, and Treatment IND. Approval
      rates for all categories exceed 99%. Approval requires FDA and Institutional
      Review Board (IRB) approval, and cooperation of the pharmaceutical partner is
      essential. "Right-to-Try" legislation bypasses some of these steps, but provides
      no regulatory or safety oversight. CONCLUSION: The FDA EA program is a reasonable
      option for patients for whom all other therapeutic interventions have failed. The
      SP-IND not only provides patient access to new drugs, but also maintains a
      balance between immediacy and necessary patient protection. Rather than
      circumventing existing FDA regulations through proposed legislation, it seems
      more judicious to provide the knowledge and means to meet the EA requirements.

PMID- 25588692
TI  - Irisin: a new molecular marker and target in metabolic disorder.
AB  - Irisin is a newly discovered exercise-mediated myokine which regulates energy
      metabolism and has been the subject of much recent research. Irisin plays an
      important role in metabolic diseases making it a potential new target to combat
      obesity and its associated disorders, such as T2DM. However, the results of
      several recent studies investigating the effects of irisin have been
      controversial. The present review will introduce the discovery of irisin, the
      role of irisin in metabolic disorders, possible mechanisms, and unanswered
      questions for future research. 

PMID- 25588693
TI  - Differential competence of redox-regulatory mechanism under extremes of
      temperature determines growth performances and cross tolerance in two indica rice
      cultivars.
AB  - The present study investigated the relationship between reactive oxygen species
      (ROS) accumulation (total and individual), antioxidant and radical scavenging
      capacity (total and individual), transcript abundance of some antioxidative genes
      and oxidative damages to membrane protein and lipid in germinating tissues of a
      salt resistant (SR26B) and salt sensitive (Ratna) rice cultivars under extremes
      of temperature to elucidate redox-regulatory mechanism governing differential
      oxidative stress tolerance associated with better growth and yield potential and
      identification of cross tolerance, if any. Imbibitional heat and chilling stress
      caused disruption of redox-homeostasis and oxidative damage to a newly assembled
      membrane system by increasing pro-oxidant/antioxidant ratio and by aggravating
      membrane lipid peroxidation and protein oxidation [measured in terms of
      accumulation of thiobarbituric acid reactive substances (TBARS), free carbonyl
      content (CO groups), and membrane protein thiol level (MPTL)]. A concomitant
      increase in accumulation of individual ROS (superoxide and hydrogen peroxide) and
      significant reduction of radical scavenging activity (assessed in terms of ABTS,
      FRAP and DPPH methods), non-enzymatic and enzymatic anti-oxidative defense
      [assessed in terms of total thiol content and activities of superoxide dismutase
      (EC 1.15.1.1), catalase (EC 1.11.1.6), ascorbate peroxidase (EC 1.11.1.11), and
      glutathione reductase (EC 1.6.4.2)] are also noticed in both the salt sensitive
      (Ratna) and resistant (SR26B) germinating tissues of rice cultivars. When
      compared, salt resistant cultivar SR26B was found to suffer significantly less
      redox-imbalance and related oxidative damages to membrane protein and lipid as
      compared to salt sensitive cultivar Ratna. The salt tolerant cultivar SR26B
      resisted imbibitional chilling and heat stress due to its early preparedness to
      combat oxidative stress by up-regulation of gene expression of anti-oxidative
      enzymes and better capacity of redox-regulation and mitigation of oxidative
      damage to membrane protein and lipid as compared to salt sensitive cultivar
      Ratna, under the same magnitude of imbibitional heat and chilling stress. A model
      for redox-homeostasis in which the ROS-antioxidant interaction acts as a
      metabolic interface for up-regulation of gene expression necessary for cross
      tolerance is also proposed. 

PMID- 25588694
TI  - Differential accumulation of glycinebetaine and choline monooxygenase in bladder
      hairs and lamina leaves of Atriplex gmelini under high salinity.
AB  - Atriplex gmelini is a halophyte and possesses bladder hairs on the leaf surface.
      It is also known to accumulate the osmoprotectant glycinebetaine (GB). However,
      it remains unclear whether GB and its biosynthetic enzyme choline monooxygenase
      (CMO) accumulate in the bladder hairs. Microscopic observation of young leaves
      showed many bladder hairs on their surfaces, but their total number decreased
      along with leaf maturity. Sodium Green fluorescent approach revealed Na(+)
      accumulation in bladder cells of young leaves when A. gmelini was grown at high
      salinity (250 mM NaCl). Due to fewer bladder hairs in mature leaves, Na(+)
      accumulation was mostly found in mesophyll cells of mature leaves under high
      salinity. GB accumulation was found at significant level in both bladder- and
      laminae-cells without any addition of NaCl and its content increased at high
      salinity. CMO was not found in bladder hairs or young leaf laminae. Instead, the
      CMO protein expression was observed in mature leaves and that showed increased
      accumulation with increasing concentration of NaCl. Furthermore, in situ
      hybridization experiments revealed the expression of a transporter gene for GB,
      AgBetT, in the bladder hairs. Based on these results, the synthesis and
      translocation of GB in A. gmelini were discussed.

PMID- 25588695
TI  - Carbon utilization by fruit limits shoot growth in alternate-bearing citrus
      trees.
AB  - Fruit load in alternate-bearing citrus trees is reported to alter shoot number
      and growth during spring, summer, and autumn flushes, and the source-sink
      balance, which affects the storage and mobilization of reserve nutrients. The aim
      of this work was to assess the extent of shoot growth inhibition resulting from
      the presence of fruits in 'Moncada' mandarin trees loaded with fruit (ON) or with
      very light fruit load (OFF), and to identify the role of carbohydrates and
      nitrogenous compounds in the competition between fruits and shoots. Growth of
      reproductive and vegetative organs was measured on a monthly basis. (13)C- and
      (15)N-labeled compounds were supplied to trace the allocation of reserve
      nutrients and subsequent translocation from source to sink. At the end of the
      year, OFF trees produced more abundant flushes (2.4- and 4.9-fold higher in
      number and biomass, respectively) than ON trees. Fruits from ON trees accumulated
      higher C amounts at the expense of developing flushes, whereas OFF trees
      exhibited the opposite pattern. An inverse relationship was identified between
      the amount of C utilized by fruits and vegetative flush growth. (13)C-labeling
      revealed an important role for mature leaves of fruit-bearing branches in
      supporting shoot/fruit growth, and the elevated sink strength of growing fruits
      on shoots. N availability for vegetative shoots was not affected by the presence
      or absence of fruits, which accumulated important amounts of (15)N. In
      conclusion, our results show that shoot growth is resource-limited as a
      consequence of fruit development, and vegetative-growth inhibition is caused by
      photoassimilate limitation. The competence for N is not a decisive factor in
      limiting vegetative growth under the experimental conditions of this study. 

PMID- 25588696
TI  - Alcohol consumption in adolescent homicide victims in the city of Johannesburg,
      South Africa.
AB  - AIMS: To describe the blood alcohol concentration (BAC) of adolescent homicide
      victims in Johannesburg, South Africa and to identify the victim and event
      characteristics associated with a positive BAC at the time of death. DESIGN:
      Logistic regression of mortality data collected by the National Injury Mortality
      Surveillance System (NIMSS). SETTING: Johannesburg, South Africa. PARTICIPANTS: A
      total of 323 adolescent (15-19 years) homicide victims for the period 2001-9 who
      had been tested for the presence of alcohol. MEASUREMENTS: Data on the victims'
      BAC level, demographics, weapon or method used, scene, day and time of death were
      drawn from NIMSS. FINDINGS: Alcohol was present in 39.3% of the homicide victims.
      Of these, 88.2% had a BAC level equivalent to or in excess of the South African
      limit of 0.05 g/100 ml for intoxication. Multivariate logistic analysis showed
      that a positive BAC in homicide victims was associated significantly with the
      victim's sex [male: odds ratio (OR) = 2.127; 95% confidence interval (CI) = 1.012
      4.471], victim's age (18-19 years: OR = 2.364; CI = 1.343-4.163); weapon used
      (sharp instruments: OR = 2.972; CI = 1.708-5.171); and time of death (weekend: OR
      = 3.149; CI = 1.842-5.383; night-time: OR = 2.175; CI = 1.243-3.804).
      CONCLUSIONS: Excessive alcohol consumption is associated with a substantial
      proportion of adolescent homicides in Johannesburg, South Africa, and is more
      prevalent among male and older adolescent victims and in victims killed with
      sharp instruments over the weekends and during the evenings.

PMID- 25588697
TI  - Direct and simultaneous quantification of tannin mean degree of polymerization
      and percentage of galloylation in grape seeds using diffuse reflectance fourier
      transform-infrared spectroscopy.
AB  - The direct and simultaneous quantitative determination of the mean degree of
      polymerization (mDP) and the degree of galloylation (%G) in grape seeds were
      quantified using diffuse reflectance infrared Fourier transform spectroscopy and
      partial least squares (PLS). The results were compared with those obtained using
      the conventional analysis employing phloroglucinolysis as pretreatment followed
      by high performance liquid chromatography-UV and mass spectrometry detection.
      Infrared spectra were recorded in solid state samples after freeze drying. The
      2nd derivative of the 1832 to 1416 and 918 to 739 cm(-1) spectral regions for the
      quantification of mDP, the 2nd derivative of the 1813 to 607 cm(-1) spectral
      region for the degree of %G determination and PLS regression were used. The
      determination coefficients (R(2) ) of mDP and %G were 0.99 and 0.98,
      respectively. The corresponding values of the root-mean-square error of
      calibration were found 0.506 and 0.692, the root-mean-square error of cross
      validation 0.811 and 0.921, and the root-mean-square error of prediction 0.612
      and 0.801. The proposed method in comparison with the conventional method is
      simpler, less time consuming, more economical, and requires reduced quantities of
      chemical reagents and fewer sample pretreatment steps. It could be a starting
      point for the design of more specific models according to the requirements of the
      wineries. 

PMID- 25588698
TI  - Alteration of structure and function of ATP synthase and cytochrome c oxidase by
      lack of Fo-a and Cox3 subunits caused by mitochondrial DNA 9205delTA mutation.
AB  - Mutations in the MT-ATP6 gene are frequent causes of severe mitochondrial
      disorders. Typically, these are missense mutations, but another type is
      represented by the 9205delTA microdeletion, which removes the stop codon of the
      MT-ATP6 gene and affects the cleavage site in the MT-ATP8/MT-ATP6/MT-CO3
      polycistronic transcript. This interferes with the processing of mRNAs for the
      Atp6 (Fo-a) subunit of ATP synthase and the Cox3 subunit of cytochrome c oxidase
      (COX). Two cases described so far presented with strikingly different clinical
      phenotypes-mild transient lactic acidosis or fatal encephalopathy. To gain more
      insight into the pathogenic mechanism, we prepared 9205delTA cybrids with
      mutation load ranging between 52 and 99% and investigated changes in the
      structure and function of ATP synthase and the COX. We found that 9205delTA
      mutation strongly reduces the levels of both Fo-a and Cox3 proteins. Lack of Fo-a
      alters the structure but not the content of ATP synthase, which assembles into a
      labile, ~60 kDa smaller, complex retaining ATP hydrolytic activity but which is
      unable to synthesize ATP. In contrast, lack of Cox3 limits the biosynthesis of
      COX but does not alter the structure of the enzyme. Consequently, the diminished
      mitochondrial content of COX and non-functional ATP synthase prevent most
      mitochondrial ATP production. The biochemical effects caused by the 9205delTA
      microdeletion displayed a pronounced threshold effect above ~90% mutation
      heteroplasmy. We observed a linear relationship between the decrease in subunit
      Fo-a or Cox3 content and the functional presentation of the defect. Therefore we
      conclude that the threshold effect originated from a gene-protein level. 

PMID- 25588699
TI  - Is Pulse Pressure an Independent Risk Factor for Incident Stroke, REasons for
      Geographic And Racial Differences in Stroke.
AB  - BACKGROUND: Pulse pressure (PP) is a potential risk factor of stroke. The
      relationship of incident stroke with systolic blood pressure (SBP), diastolic
      blood pressure (DBP), mean arterial pressure (MAP), and PP was examined. METHODS:
      Data were from the REasons for Geographic And Racial Differences in Stroke
      national cohort study of 30,239 black and white participants aged >=45 years,
      enrolled between 2003 and 2007. PP (SBP-DBP) and MAP (MAP = DBP + 1/3*PP) were
      calculated. Telephone follow-up occurred every six months for self or proxy
      reported suspected stroke events, confirmed using expert adjudication. Cox
      proportional hazards models examined the association of incident stroke for the
      different BP measurements with multivariable adjustment for sociodemographic and
      clinical risk factors including gender and race. RESULTS: Men and women without
      prevalent stroke at baseline were analyzed (n = 25,462). During follow-up (mean
      6.3+/-2.3 years, maximum 10 years), 916 strokes occurred. Unadjusted PP (hazard
      ratio [HR] = 1.30; 95% confidence interval [CI] 1.24-1.35), SBP (HR = 1.22; 95%
      CI 1.18-1.32), MAP (HR = 1.24; 95% CI 1.16-1.32), and DBP (HR = 1.09; 95% CI 1.01
      1.17) were associated with stroke risk; however, after adjustment for SBP and
      other risk factors, the association with PP was attenuated (HR = 0.98; 95% CI
      0.90-1.07), whereas SBP persisted as a predictor (HR = 1.14; 95% CI 1.06-1.23).
      These associations were consistent across age (younger vs. older >70 years) and
      race (black vs. white). CONCLUSIONS: PP is positively associated with incident
      stroke, but not independently from SBP; and, there were no significant gender,
      racial, or regional differences in that association.

PMID- 25588700
TI  - R Wave in aVL Lead is a Robust Index of Left Ventricular Hypertrophy: A Cardiac
      MRI Study.
AB  - BACKGROUND: In patients free from overt cardiac disease, R wave in aVL lead
      (RaVL) is strongly correlated with left ventricular mass index (LVMI) assessed by
      transthoracic echocardiography. The aim of the present study was to extend this
      finding to other settings (cardiomyopathy or conduction disorders), by comparing
      ECG criteria of left ventricular hypertrophy (LVH) to cardiac MRI (CMR). METHODS:
      In 501 patients, CMR and ECG were performed within a median-period of 5 days. CMR
      LVH cut-offs used were 83 g/m2 in men and 67 g/m2 in women. RESULTS: RaVL was
      independently correlated with LVMI in patients with or without myocardial
      infarction (MI) (N = 300 and N = 201, respectively). SV3 was independently
      correlated with LVMI and LV enlargement only in patients without MI. In the whole
      cohort, RaVL had area under receiver-operating characteristic curve of 0.729
      (specificity 98.3%, sensitivity 19.6%, optimal cut-off 1.1 mV). The performance
      of RaVL was remarkable in women, in Caucasians, and in the presence of right
      bundle branch block. It decreased in case of MI. Overall, it is proposed that
      below 0.5 mV and above 1.0 mV, RaVL is sufficient to exclude or establish LVH.
      Between 0.5 and 1 mV, composite indices (Cornell voltage or product) should be
      used. Using this algorithm allowed classifying appropriately 85% of the patients.
      CONCLUSIONS: Our results showed that RaVL is a good index of LVH with a univocal
      threshold of 1.0 mV in various clinical conditions. SV3 may be combined to RaVL
      in some conditions, namely LV enlargement to increase its performance.

PMID- 25588702
TI  - Portable oxidative stress sensor: dynamic and non-invasive measurements of
      extracellular H2O2 released by algae.
AB  - Reactive oxygen species (ROS) generated by aerobic organisms are essential for
      physiological processes such as cell signaling, apoptosis, immune defense and
      oxidative stress mechanisms. Unbalanced oxidant/antioxidant budgets are involved
      in many diseases and, therefore, the sensitive measurement of ROS is of great
      interest. Here, we present a new device for the real-time monitoring of oxidative
      stress by measuring one of the most stable ROS, namely hydrogen peroxide (H2O2).
      This portable oxidative stress sensor contains the heme protein cytochrome c (cyt
      c) as sensing element whose spectral response enables the detection of H2O2 down
      to a detection limit of 40 nM. This low detection limit is achieved by
      introducing cyt c in a random medium, enabling multiscattering that enhances the
      optical trajectory through the cyt c spot. A contact microspotting technique is
      used to produce reproducible and reusable cyt c spots which are stable for
      several days. Experiments in static and microfluidic regimes, as well as
      numerical simulations demonstrate the suitability of the cyt c/H2O2 reaction
      system for the real-time sensing of the kinetics of biological processes without
      H2O2 depletion in the measurement chamber. As an example, we detect the release
      of H2O2 from the green alga Chlamydomonas reinhardtii exposed to either 180 nM
      functionalized CdSe/ZnS core shell quantum dots, or to 10 mg/l TiO2
      nanoparticles. The continuous measurement of extracellular H2O2 by this optical
      sensor with high sensitivity is a promising new means for real-time cytotoxicity
      tests, the investigation of oxidative stress and other physiological cell
      processes.

PMID- 25588701
TI  - Salivary alpha amylase diurnal pattern and stress response are associated with
      body mass index in low-income preschool-aged children.
AB  - Physiological stress responses are proposed as a pathway through which stress can
      "get under the skin" and lead to health problems, specifically obesity. We tested
      associations of salivary alpha amylase (sAA) diurnal patterns and stress
      responses with body mass index (BMI) in young, low-income children (51% male; 54%
      non-Hispanic white). Diurnal saliva samples were collected three times per day
      across three days for 269 children (M age 50.8 months, SD 6.3). Individual sAA
      intercept and slope values were calculated using random effect models to
      represent morning sAA levels and rate of sAA change across the day. A subset of
      children (n=195; M age 56.6 months, SD 6.9) participated in a lab-based
      behavioral stress protocol. Area under the curve increase (AUCI) across four
      timepoints was calculated to represent increase in sAA output during stress
      elicitation. Children were weighed and height measured and BMI z-score was
      calculated. Linear regression was used to evaluate associations of sAA intercept,
      sAA slope, and sAA AUCI with BMI z-score, controlling for child age, sex, and
      race/ethnicity; maternal weight status; and family income-to-needs ratio. Diurnal
      and stress-response sAA patterns were related to child adiposity: for each 1
      standard deviation unit (SDU) decrease in morning sAA level, the child's BMI z
      score increased by 0.11 (SE 0.05) SDU's (p<.04); for each 1-SDU increase in sAA
      slope across the day, the child's BMI z-score increased by 0.12 (SE 0.05) SDU's
      (p<.03); and for each 1-SDU decrease in sAA AUCI during the stress elicitation,
      the child's BMI z-score increased by 0.14 (SE 0.06) SDU's (p<.03). Blunted stress
      responses and atypical diurnal patterns of sAA have been found following exposure
      to chronic life stressors such as poverty. Findings suggest that associations of
      stress, sAA, and elevated body mass index may develop very early in the lifespan.

PMID- 25588703
TI  - A facile fluorescence method for versatile biomolecular detection based on
      pristine alpha-Fe2O3 nanoparticle-induced fluorescence quenching.
AB  - This work investigated the interactions of alpha-Fe2O3 nanoparticles (NPs) with
      different structural nucleic acids and their fluorescence quenching ability
      towards fluorophore-labelled nucleic acid probes. Different from bulk alpha-Fe2O3
      samples, nanoscale alpha-Fe2O3 particles exhibit the unique properties of strong
      adsorption and fluorescence quenching to fluorophore-labelled single-stranded DNA
      (ssDNA) probes. Based on these findings, a facile fluorescence method was
      developed for versatile quantification of nucleic acids. The size scale of NPs
      makes a significant impact on this sensing platform. Better selectivity was given
      by bigger NP (50-100 nm)-based nucleic acid-sensing platform compared with
      smaller NP (30 nm)-based one. In the 50-100 nm alpha-Fe2O3 NP-based sensing
      platform, single nucleotide mismatch or single base-pair mismatch can even be
      effectively discriminated. The targets of micro-RNA (miRNA), ssDNA and double
      stranded DNA (dsDNA) are sensitively detected with detection limits of 0.8 nM,
      1.1 nM and 0.64 nM (S/N=3), respectively. Significantly, alpha-Fe2O3 NPs possess
      different affinities towards ssDNA probes with different lengths, and can be used
      as a universal quencher for ssDNA probes labelled with different fluorescent
      dyes. On the basis of these properties, the pristine alpha-Fe2O3 NPs hold the
      potential to be widely utilized in the development of novel biosensors with
      signal amplification or simultaneous multiple target detection strategies.

PMID- 25588704
TI  - Kidney transplant recipients carrying the CYP3A4*22 allelic variant have reduced
      tacrolimus clearance and often reach supratherapeutic tacrolimus concentrations.
AB  - CYP3A4*22 is an allelic variant of the cytochrome P450 3A4 associated with a
      decreased activity. Carriers of this polymorphism may require reduced tacrolimus
      (Tac) doses to reach the target residual concentrations (Co). We tested this
      hypothesis in a population of kidney transplant recipients extracted from a
      multicenter, prospective and randomized study. Among the 186 kidney transplant
      recipients included, 9.3% (18 patients) were heterozygous for the CYP3A4*22
      genotype and none were homozygous (allele frequency of 4.8%). Ten days after
      transplantation (3 days after starting treatment with Tac), 11% of the CYP3A4*22
      carriers were within the target range of Tac Co (10-15 ng/mL), whereas among the
      CYP3A4*1/*1 carriers, 40% were within the target range (p = 0.02, OR = 0.19
      [0.03; 0.69]). The mean Tac Co at day 10 in the CYP3A4*1/*22 group was 23.5 ng/mL
      (16.6-30.9) compared with 15.1 ng/mL (14-16.3) in the CYP3A4*1/*1 group, p <
      0.001. The Tac Co/dose significantly depended on the CYP3A4 genotype during the
      follow-up (random effects model, p < 0.001) with the corresponding equivalent
      dose for patients heterozygous for CYP3A4*22 being 0.67 [0.54; 0.84] times the
      dose for CYP3A4*1/*1 carriers. In conclusion, the CYP3A4*22 allelic variant is
      associated with a significantly altered Tac metabolism and carriers of this
      polymorphism often reach supratherapeutic concentrations.

PMID- 25588706
TI  - The electrical network of maize root apex is gravity dependent.
AB  - Investigations carried out on maize roots under microgravity and hypergravity
      revealed that gravity conditions have strong effects on the network of plant
      electrical activity. Both the duration of action potentials (APs) and their
      propagation velocities were significantly affected by gravity. Similarly to what
      was reported for animals, increased gravity forces speed-up APs and enhance
      synchronized electrical events also in plants. The root apex transition zone
      emerges as the most active, as well as the most sensitive, root region in this
      respect. 

PMID- 25588705
TI  - Liposome encapsulated zoledronate favours M1-like behaviour in murine macrophages
      cultured with soluble factors from breast cancer cells.
AB  - BACKGROUND: Tumour stromal macrophages differentiate to tumour-associated
      macrophages (TAMs) with characteristics of immunosuppressive M2-type macrophages,
      having a central role in promoting tumour vascularisation, cancer cell
      dissemination and in suppressing anti-cancer immune responses. Bisphosphonates
      (BPs) are a group of drugs commonly used as anti-resorptive agents. Further,
      nitrogen containing BPs like Zoledronate (ZOL), are known to cause unspecific
      inflammatory reactions hence the hypothesis that its use could modulate TAMs
      polarization toward a more inflammatory phenotype. METHODS: We studied the in
      vitro polarization of J774 murine macrophages upon culture in 4T1 breast cancer
      cell-conditioned medium (4T1CM) and stimulation with LPS and free and liposome
      encapsulated bisphosphonates. RESULTS: In this system, breast cancer soluble
      factors reduced the pro-inflammatory activation of macrophages but increased the
      secretion of matrix metalloproteinases (MMPs). In the presence of 4T1CM, a non
      cytotoxic dose of liposome-encapsulated ZOL (ZOL-LIP) enhanced the expression of
      iNOS and TNF-alpha, markers of M1 activation, but did not diminish the expression
      of M2-type markers. In contrast, clodronate treatment either as a free drug (CLO)
      or liposome-encapsulated (CLO-LIP) decreased the expression of the M1-type
      markers and was highly cytotoxic to the macrophages. CONCLUSIONS: Breast cancer
      cells soluble factors modulate macrophages toward M2 activation state.
      Bisphosphonates may be applied to counteract this modulation. We propose that ZOL
      LIP may be suitable for favouring cytotoxic immune responses by TAMs in breast
      cancer, whereas CLO-LIP may be appropriate for TAM depletion.

PMID- 25588707
TI  - Anatomical and Scanning Electron Microscopic Study of the Tongue in the Meerkat
      (Suricata suricatta, Schreber, 1776).
AB  - This research presents the first anatomical description of the tongue and lingual
      papillae of the meerkat and compares the different information on the morphology
      of the other carnivore species. For this purpose, three tongues were used as
      material. The tongue was elongated with an oval or rounded apex. On the dorsal
      and ventrolateral surfaces of the tongue, filiform papillae had extent variations
      in morphology. Papillary body of each filiform papilla on the ventrolateral
      surface of the lingual body was ramified into 2-5 glovelike projections, and all
      pointed tips of these projections were directed caudally. On the dorsal lingual
      surface, each filiform papilla leaned on another without any space and both
      lateral borders of each filiform papilla included 4-6 small secondary projections
      or spines. A few rounded fungiform papillae were randomly distributed and
      embedded among the filiform papillae. On the caudal one-third of the body, there
      were two elongated circumvallate papillae. Some superficial fissures and taste
      pores were detected on the flat surfaces of each circumvallate papilla which was
      surrounded by a prominent and continuous gustatory groove. On the radix of the
      tongue, numerous dome-shaped protuberances of lingual salivary glands beneath the
      epithelium and one centrally located orificium was very invincible on the convex
      surface of each protuberance. Anatomical distribution of lingual papillae
      differed from those of other carnivores and represented morphological adaptation
      to the food type and feeding habits. 

PMID- 25588708
TI  - Biological interaction of living cells with COSAN-based synthetic vesicles.
AB  - Cobaltabisdicarbollide (COSAN) [3,3'-Co(1,2-C2B9H11)2](-), is a complex boron
      based anion that has the unusual property of self-assembly into membranes and
      vesicles. These membranes have similar dimensions to biological membranes found
      in cells, and previously COSAN has been shown to pass through synthetic lipid
      membranes and those of living cells without causing breakdown of membrane barrier
      properties. Here, we investigate the interaction of this inorganic membrane
      system with living cells. We show that COSAN has no immediate effect on cell
      viability, and cells fully recover when COSAN is removed following exposure for
      hours to days. COSAN elicits a range of cell biological effects, including
      altered cell morphology, inhibition of cell growth and, in some cases, apoptosis.
      These observations reveal a new biology at the interface between inorganic,
      synthetic COSAN membranes and naturally occurring biological membranes. 

PMID- 25588709
TI  - Prevalence of Gender Nonconformity in Flanders, Belgium.
AB  - Gender nonconformity refers to the extent to which a person's gender identity,
      gender role and/or gender expression differs from the cultural norms prescribed
      for people of a particular sex, within a certain society and era. Most data on
      gender nonconformity focus on the prevalence of gender dysphoria (which also
      includes a distress factor) or on the number of legal sex changes. However, not
      every gender nonconforming individual experiences distress or applies for
      treatment. Population-based research on the broad spectrum of gender
      nonconformity is scarce and more information on the variance outside the gender
      binary is needed. This study aimed to examine the prevalence of gender
      incongruence (identifying stronger with the other sex than with the sex assigned
      at birth) and gender ambivalence (identifying equally with the other sex as with
      the sex assigned at birth) based on two population-based surveys, one of 1,832
      Flemish persons and one of 2,472 sexual minority individuals in Flanders. In the
      general population, gender ambivalence was present in 2.2 % of male and 1.9 % of
      female participants, whereas gender incongruence was found in 0.7 % of men and
      0.6 % of women. In sexual minority individuals, the prevalence of gender
      ambivalence and gender incongruence was 1.8 and 0.9 % in men and 4.1 and 2.1 % in
      women, respectively. With a current Flemish population of about 6 million, our
      results indicate a total of between 17,150 and 17,665 gender incongruent men and
      between 14,473 and 15,221 gender incongruent women in Flanders.

PMID- 25588710
TI  - Development of a high affinity, non-covalent biologic to add functionality to
      Fabs.
AB  - Functionalization of monoclonal antibodies (mAbs) requires chemical
      derivatization and/or genetic manipulation. Inherent in these methods are
      challenges with protein heterogeneity, stability and solubility. Such
      perturbations could potentially be avoided by using a high affinity, non-covalent
      intermediate to bridge the desired functionality to a stable mAb. Recently, we
      engineered a binding site for a peptide named "meditope" within the Fab of
      trastuzumab. Proximity of the meditope site to that of protein L suggested an
      opportunity to enhance the meditope's moderate affinity. Joined by a peptide
      linker, the meditope-protein L construct has a KD ~ 180 pM - a 7000-fold increase
      in affinity. The construct is highly specific to the engineered trastuzumab, as
      demonstrated by flow cytometry. Moreover, the fusion of a bulky GFP to this
      construct did not affect the association with cell surface antigens.
      Collectively, these data indicate this specific, high affinity construct can be
      developed to rapidly add new functionality to mAbs.

PMID- 25588712
TI  - Increased risk of depressive disorder following a diagnosis of neovascular age
      related macular degeneration.

PMID- 25588711
TI  - [The PLIF and TLIF techniques. Indication, technique, advantages, and
      disadvantages].
AB  - BACKGROUND: Posterior fusion procedures (posterior lumbar interbody fusion, PLIF;
      transforaminal lumbar interbody fusion, TLIF) are long-established surgical
      techniques for lumbar interbody fusion. They differ from anterior lumbar
      interbody fusion (ALIF) and extreme lateral interbody fusion (XLIF) procedures by
      approach and associated complications. OBJECTIVES: The posterior fusion
      procedures PLIF and TLIF are presented and compared with other fusion methods,
      including advantages and disadvantages. Furthermore, the surgical technique and
      their complications are described. Based on the current literature, it is
      discussed which surgical techniques can be used in various cases. MATERIALS AND
      METHODS: A PubMed search of "posterior spinal fusion treatments" and the clinical
      experience of the authors are summarized in this review article. RESULTS: PLIF
      and TLIF procedures reduced back and leg pain, restored the sagittal profile of
      the lumbar spine, and achieved good fusion rates and long-term stability.
      Advantages of the TLIF procedure include shorter operative times, less blood
      loss, less intraoperative risk of injury to neural structures, and shorter
      convalescence. Compared with the interposition of a cage in the ALIF technique, a
      further step with the risk of vascular injury is eliminated. CONCLUSIONS: The
      PLIF and TLIF procedures are almost equivalent posterior fusion procedures with
      high fusion rates, good long-term clinical outcomes, and low risk of
      complications. The TLIF procedure is slightly advantageous: lower nerve
      irritation rates, shorter operative times, and less extensive operation. Thus,
      the TLIF procedure is available for cases with single-sided pathologies and the
      PLIF procedure is available for bilateral compressions.

PMID- 25588714
TI  - Adult choledochal cysts: current update on classification, pathogenesis, and
      cross-sectional imaging findings.
AB  - Approximately 20% of choledochal cysts (CC) present in adult patients and they
      are commonly associated with a high risk of complications, including malignancy.
      Additionally, children who underwent internal drainage procedures for CCs can
      develop complications during adulthood despite treatment. Concepts regarding
      classification and pathogenesis of the CCs have been evolving. While new subtypes
      are being added to the widely accepted Todani classification system, simplified
      classification schemes have also been proposed to guide appropriate management.
      The exact etiology of CCs is currently unknown. The two leading theories involve
      either the presence of an anomalous pancreatico-biliary junction with associated
      reflux of pancreatic juice into the biliary system or, more recently, some form
      of antenatal biliary obstruction with resulting proximal bile duct dilation.
      Imaging studies play an important role in the initial diagnosis, surgical
      planning, and long-term surveillance of CCs. 

PMID- 25588713
TI  - Sustained virological response to antiviral therapy in a randomized trial of
      cyclosporine versus tacrolimus in liver transplant patients with recurrent
      hepatitis C infection.
AB  - BACKGROUND: Choice of calcineurin inhibitor may influence response to antiviral
      therapy in liver transplant patients with hepatitis C virus (HCV) infection.
      MATERIAL AND METHODS: In a randomized, multicenter, 80-week trial, liver
      transplant recipients (>6 months and L10 years post-transplant) with recurrent
      HCV infection received cyclosporine (n=50) or tacrolimus (n=42) with a 48-week
      course of pegylated interferon (peg-IFNalpha2a) and ribavirin. Twenty-three
      patients in each group completed the trial on study medication. The primary
      endpoint was sustained virological response (SVR) 24 weeks after the end of
      antiviral therapy, for which 43 patients were eligible for analysis. RESULTS: The
      rate of SVR was 60.0% (12/20) with cyclosporine and 43.5% (10/23) with tacrolimus
      (adjusted odds ratio 1.85; 95% CI 0.53-6.43; p=0.331). There were no significant
      intergroup differences for rapid or early virological response, relapse, HCV RNA
      viral load, or fibrosis progression. One cyclosporine-treated patient experienced
      acute rejection. One patient died in each group. Adverse events, treatment
      related adverse events, and serious adverse events were similar between groups.
      CONCLUSIONS: Since fewer patients were recruited than planned (92 versus 355),
      the study was underpowered and robust conclusions cannot be drawn regarding the
      effect of cyclosporine and tacrolimus on virological responses to antiviral
      treatment for recurrent HCV after liver transplantation. However, as reported in
      other trials, SVR was higher in cyclosporine-treated patients.

PMID- 25588715
TI  - Contrast-enhanced ultrasound (CEUS) of cystic and solid renal lesions: a review.
AB  - Incidentally detected renal lesions have traditionally undergone imaging
      characterization by contrast-enhanced computer tomography (CECT) or magnetic
      resonance imaging. Contrast-enhanced ultrasound (CEUS) of renal lesions is a
      relatively novel, but increasingly utilized, diagnostic modality. CEUS has
      advantages over CECT and MRI including unmatched temporal resolution due to
      continuous real-time imaging, lack of nephrotoxicity, and potential cost savings.
      CEUS has been most thoroughly evaluated in workup of complex cystic renal
      lesions, where it has been proposed as a replacement for CECT. Using CEUS to
      differentiate benign from malignant solid renal lesions has also been studied,
      but has proven difficult due to overlapping imaging features. Monitoring
      minimally invasive treatments of renal masses is an emerging application of CEUS.
      An additional promising area is quantitative analysis of renal masses using CEUS.
      This review discusses the scientific literature on renal CEUS, with an emphasis
      on imaging features differentiating various cystic and solid renal lesions. 

PMID- 25588717
TI  - Utility of endoscopy for diagnosis of barrett in a non-Western society:
      endoscopic and histopathologic correlation.
AB  - Barrett esophagus is metaplastic transformation of esophageal squamous epithelium
      to columnar cells. A total of 1370 patients who had undergone upper endoscopy
      because of dyspeptic complaints were enrolled in the study. Age, sex, alcohol and
      smoking habits, body mass index, type and duration of symptoms (heartburn,
      epigastric pain, nausea, vomiting), and use of proton pump inhibitors were
      evaluated in all patients and recorded on standardized forms. Patients were
      grouped as normal esophagogastric junction, long-segment Barrett esophagus, and
      short-segment Barrett. Biopsies were taken from at least 6 points and examined
      histopathologically. Of the 1370 patients involved in the study, 748 (54.6%) were
      female and 622 (45.4%) were male. Mean age was 47.2 +/- 15.30 years. Short
      segment Barrett esophagus was detected in 16 patients, and long-segment Barrett
      was detected in 11 patients. Although Barrett esophagus was detected in 11 cases
      that were suspected to have Barrett during endoscopy, histopathology was negative
      in all cases that were not suspected to have Barrett. Barrett esophagus
      prevalence was significantly higher in people who used alcohol and tobacco and
      who had hiatal hernia. Although Barrett esophagus was detected in 40% of cases
      that were suspected to have Barrett during endoscopy, histopathology was negative
      in all cases that were not suspected to have Barrett. Barrett was detected in
      40.7% of cases that were suspected to have Barrett during endoscopy;
      histopathology was negative in all cases that were not suspected to have Barrett.
      Senstivity of endoscopy is questionable in detection of short-segment Barrett. 

PMID- 25588719
TI  - lncRNA-MFDL: identification of human long non-coding RNAs by fusing multiple
      features and using deep learning.
AB  - Long noncoding RNAs (lncRNAs) are emerging as a novel class of noncoding RNAs and
      potent gene regulators, which play an important and varied role in cellular
      functions. lncRNAs are closely related with the occurrence and development of
      some diseases. High-throughput RNA-sequencing techniques combined with de novo
      assembly have identified a large number of novel transcripts. The discovery of
      large and 'hidden' transcriptomes urgently requires the development of effective
      computational methods that can rapidly distinguish between coding and long
      noncoding RNAs. In this study, we developed a powerful predictor (named as lncRNA
      MFDL) to identify lncRNAs by fusing multiple features of the open reading frame,
      k-mer, the secondary structure and the most-like coding domain sequence and using
      deep learning classification algorithms. Using the same human training dataset
      and a 10-fold cross validation test, lncRNA-MFDL can achieve 97.1% prediction
      accuracy which is 5.7, 3.7, and 3.4% higher than that of CPC, CNCI and lncRNA
      FMFSVM predictors, respectively. Compared with CPC and CNCI predictors in other
      species (e.g., anole lizard, zebrafish, chicken, gorilla, macaque, mouse,
      lamprey, orangutan, xenopus and C. elegans) testing datasets, the new lncRNA-MFDL
      predictor is also much more effective and robust. These results show that lncRNA
      MFDL is a powerful tool for identifying lncRNAs. The lncRNA-MFDL software package
      is freely available at for academic users. 

PMID- 25588718
TI  - Controlling two-step multimode switching of dihydroazulene photoswitches.
AB  - We present the synthesis and switching studies of systems with two photochromic
      dihydroazulene (DHA) units connected by a phenylene bridge at either para or meta
      positions, which correspond to a linear or cross-conjugated pathway between the
      photochromes. According to UV/Vis absorption and NMR spectroscopic measurements,
      the meta-phenylene-bridged DHA-DHA exhibited sequential light-induced ring
      openings of the two DHA units to their corresponding vinylheptafulvenes (VHFs).
      Initially, the VHF-DHA species was generated, and, ultimately, after continued
      irradiation, the VHF-VHF species. Studies in different solvents and quantum
      chemical calculations indicate that the excitation of DHA-VHF is no longer a
      local DHA excitation but a charge-transfer transition that involves the
      neighboring VHF unit. For the linearly conjugated para-phenylene-bridged dimer,
      electronic communication between the two units is so efficient that the
      photoactivity is reduced for both the DHA-DHA and DHA-VHF species, and DHA-DHA,
      DHA-VHF, and VHF-VHF were all present during irradiation. In all, by changing the
      bridging unit, we can control the degree of stepwise photoswitching. 

PMID- 25588720
TI  - Unmanned aerial mass spectrometer systems for in-situ volcanic plume analysis.
AB  - Technology advances in the field of small, unmanned aerial vehicles and their
      integration with a variety of sensor packages and instruments, such as miniature
      mass spectrometers, have enhanced the possibilities and applications of what are
      now called unmanned aerial systems (UAS). With such technology, in situ and
      proximal remote sensing measurements of volcanic plumes are now possible without
      risking the lives of scientists and personnel in charge of close monitoring of
      volcanic activity. These methods provide unprecedented, and otherwise
      unobtainable, data very close in space and time to eruptions, to better
      understand the role of gas volatiles in magma and subsequent eruption products.
      Small mass spectrometers, together with the world's smallest turbo molecular
      pump, have being integrated into NASA and University of Costa Rica UAS platforms
      to be field-tested for in situ volcanic plume analysis, and in support of the
      calibration and validation of satellite-based remote sensing data. These new UAS
      MS systems are combined with existing UAS flight-tested payloads and assets, such
      as temperature, pressure, relative humidity, SO2, H2S, CO2, GPS sensors, on-board
      data storage, and telemetry. Such payloads are capable of generating real time 3D
      concentration maps of the Turrialba volcano active plume in Costa Rica, while
      remote sensing data are simultaneously collected from the ASTER and OMI space
      borne instruments for comparison. The primary goal is to improve the
      understanding of the chemical and physical properties of emissions for mitigation
      of local volcanic hazards, for the validation of species detection and abundance
      of retrievals based on remote sensing, and to validate transport models. 

PMID- 25588716
TI  - Targeting interferon response genes sensitizes aromatase inhibitor resistant
      breast cancer cells to estrogen-induced cell death.
AB  - INTRODUCTION: Estrogen deprivation using aromatase inhibitors (AIs) is currently
      the standard of care for postmenopausal women with hormone receptor-positive
      breast cancer. Unfortunately, the majority of patients treated with AIs
      eventually develop resistance, inevitably resulting in patient relapse and,
      ultimately, death. The mechanism by which resistance occurs is still not
      completely known, however, recent studies suggest that impaired/defective
      interferon signaling might play a role. In the present study, we assessed the
      functional role of IFITM1 and PLSCR1; two well-known interferon response genes in
      AI resistance. METHODS: Real-time PCR and Western blot analyses were used to
      assess mRNA and protein levels of IFITM1, PLSCR1, STAT1, STAT2, and IRF-7 in AI
      resistant MCF-7:5C breast cancer cells and AI-sensitive MCF-7 and T47D cells.
      Immunohistochemistry (IHC) staining was performed on tissue microarrays
      consisting of normal breast tissues, primary breast tumors, and AI-resistant
      recurrence tumors. Enzyme-linked immunosorbent assay was used to quantitate
      intracellular IFNalpha level. Neutralizing antibody was used to block type 1
      interferon receptor IFNAR1 signaling. Small interference RNA (siRNA) was used to
      knockdown IFITM1, PLSCR1, STAT1, STAT2, IRF-7, and IFNalpha expression. RESULTS:
      We found that IFITM1 and PLSCR1 were constitutively overexpressed in AI-resistant
      MCF-7:5C breast cancer cells and AI-resistant tumors and that siRNA knockdown of
      IFITM1 significantly inhibited the ability of the resistant cells to proliferate,
      migrate, and invade. Interestingly, suppression of IFITM1 significantly enhanced
      estradiol-induced cell death in AI-resistant MCF-7:5C cells and markedly
      increased expression of p21, Bax, and Noxa in these cells. Significantly elevated
      level of IFNalpha was detected in AI-resistant MCF-7:5C cells compared to
      parental MCF-7 cells and suppression of IFNalpha dramatically reduced IFITM1,
      PLSCR1, p-STAT1, and p-STAT2 expression in the resistant cells. Lastly,
      neutralizing antibody against IFNAR1/2 and knockdown of STAT1/STAT2 completely
      suppressed IFITM1, PLSCR1, p-STAT1, and p-STAT2 expression in the resistant
      cells, thus confirming the involvement of the canonical IFNalpha signaling
      pathway in driving the overexpression of IFITM1 and other interferon-stimulated
      genes (ISGs) in the resistant cells. CONCLUSION: Overall, these results
      demonstrate that constitutive overexpression of ISGs enhances the progression of
      AI-resistant breast cancer and that suppression of IFITM1 and other ISGs
      sensitizes AI-resistant cells to estrogen-induced cell death.

PMID- 25588722
TI  - Maximizing ion transmission from atmospheric pressure into the vacuum of mass
      spectrometers with a novel electrospray interface.
AB  - We have discovered that an electrode containing a conical channel with a small
      angular divergence can transmit into the vacuum almost 100% of an electrospray
      ion current produced at atmospheric pressure. Our first implementation of such a
      conical duct, which we term "ConDuct," uses a conductive plastic pipette tip
      containing an approximately 1.6 degrees  divergent channel at its entrance. We
      observed that the beam formed by the ConDuct electrode has a very low divergence
      (less than 1 degrees ) and persists for long distances in vacuum. Intrigued by
      these properties, we incorporated this electrode into a novel atmosphere-to
      vacuum ion transmission interface, and devised a technique for evaluating its
      performance relative to the commercial reference interfaces that contain heated
      metal capillaries. We determined that our new interface transmits at least 400
      times more ions than the commercial Thermo LCQ DECA XP atmosphere-to-vacuum
      interface and 2 to 3 times more than the commercial interface in the Thermo Velos
      Orbitrap and the Q Exactive mass spectrometers. We conclude that it might be
      possible to optimize the properties of the transmitted ions further by
      manufacturing ConDuct inlet electrodes from metal rather than conductive plastic
      and by determining the optimum angle of channel divergence and channel length. 

PMID- 25588723
TI  - Concise review: bullseye: targeting cancer stem cells to improve the treatment of
      gliomas by repurposing disulfiram.
AB  - Cancer stem cells (CSCs) are thought to be at the root of cancer recurrence
      because they resist conventional therapies and subsequently reinitiate tumor cell
      growth. Thus, targeting CSCs could be the bullseye to successful cancer
      therapeutics in the future. Brain tumors are some of the most challenging types
      of cancer to treat and the median survival following the initial diagnosis is 12
      18 months. Among the different types of brain tumors, glioblastoma (GBM) is
      considered the most aggressive and remains extremely difficult to treat. Despite
      surgery, radiation, and chemotherapy, most patients develop refractory disease.
      Temozolomide (TMZ) is a chemotherapy used to treat GBM however resistance
      develops in most patients. The underlying mechanisms for TMZ resistance (TMZ
      resistant) involve the expression of DNA repair gene O(6)-methylguanine-DNA
      methyltransferase. CSC genes such as Sox-2, BMI-1, and more recently Y-box
      binding protein-1 also play a role in resistance. In order to develop novel
      therapies for GBM, libraries of small interfering RNAs and off-patent drugs have
      been screened. Over the past few years, several independent laboratories
      identified disulfiram (DSF) as an off-patent drug that kills GBM CSCs. Reportedly
      DSF has several modes of action including its ability to inhibit aldehyde
      dehydrogenases, E3 ligase, polo-like kinase 1, and NFkB. Due to the fact that GBM
      is a disease of heterogeneity, chemotherapy with multitargeting properties may be
      the way of the future. In broader terms, DSF kills CSCs from a range of different
      cancer types further supporting the idea of repurposing it for "target practice."

PMID- 25588725
TI  - Signal transduction.

PMID- 25588721
TI  - Sample multiplexing with cysteine-selective approaches: cysDML and cPILOT.
AB  - Cysteine-selective proteomics approaches simplify complex protein mixtures and
      improve the chance of detecting low abundant proteins. It is possible that
      cysteinyl-peptide/protein enrichment methods could be coupled to isotopic
      labeling and isobaric tagging methods for quantitative proteomics analyses in as
      few as two or up to 10 samples, respectively. Here we present two novel cysteine
      selective proteomics approaches: cysteine-selective dimethyl labeling (cysDML)
      and cysteine-selective combined precursor isotopic labeling and isobaric tagging
      (cPILOT). CysDML is a duplex precursor quantification technique that couples
      cysteinyl-peptide enrichment with on-resin stable-isotope dimethyl labeling.
      Cysteine-selective cPILOT is a novel 12-plex workflow based on cysteinyl-peptide
      enrichment, on-resin stable-isotope dimethyl labeling, and iodoTMT tagging on
      cysteine residues. To demonstrate the broad applicability of the approaches, we
      applied cysDML and cPILOT methods to liver tissues from an Alzheimer's disease
      (AD) mouse model and wild-type (WT) controls. From the cysDML experiments, an
      average of 850 proteins were identified and 594 were quantified, whereas from the
      cPILOT experiment, 330 and 151 proteins were identified and quantified,
      respectively. Overall, 2259 unique total proteins were detected from both cysDML
      and cPILOT experiments. There is tremendous overlap in the proteins identified
      and quantified between both experiments, and many proteins have AD/WT fold-change
      values that are within ~20% error. A total of 65 statistically significant
      proteins are differentially expressed in the liver proteome of AD mice relative
      to WT. The performance of cysDML and cPILOT are demonstrated and advantages and
      limitations of using multiple duplex experiments versus a single 12-plex
      experiment are highlighted. 

PMID- 25588729
TI  - Long-term outcome of 424 childhood-onset myasthenia gravis patients.
AB  - The objective of this study was to describe the clinical characteristics, outcome
      and factors that may affect the outcome of childhood-onset myasthenia gravis
      (CMG) patients in China. We have followed up 424 patients with CMG for at least 5
      years at Tongji Hospital. At the end of follow-up, the outcome of all the
      patients was measured according to MGFA Post-intervention Status. In this study,
      the patients have been followed up for 9.8 +/- 5.4 years. The mean onset age was
      5.4 +/- 3.6 years. Ocular myasthenia gravis (OMG) was the major type of CMG
      within 2 years after onset (95%). Thymic hyperplasia was found in 116 patients,
      and thymoma was confirmed in 6 patients. Acetylcholine receptor antibodies were
      elevated in 69.5% of the patients. All the patients were routinely treated.
      Thymectomy was performed in 34 patients (8.0%). At the end of follow-up, seventy
      one patients (16.7%) were significantly improved, 66 patients (15.6%) remained
      unchanged, 53 patients (12.5%) were worsened, and 234 patients (55.2%) were
      exacerbated. Importantly, fifty OMG patients (12.4%) had transformed into
      generalized myasthenia gravis (GMG) over 2 years after onset. Thymectomy did not
      effectively reduce the transformation from OMG to GMG. However, GMG cases
      significantly benefited from the surgery. This study indicated that the cases
      with autoimmune CMG account for over 50% in Chinese MG population. The long-term
      follow-up discloses that CMG patients have a low percentage of improvement, and a
      high percentage of worsening and exacerbation. The treatment should not be
      withdrawn too early after the patients obtain complete stable remission. More
      studies are needed to gain better control of CMG symptoms.

PMID- 25588730
TI  - MuSK myasthenia gravis as a manifestation of immune restoration disease in an HIV
      positive patient.

PMID- 25588732
TI  - Palpitations and dizziness in a 64-year-old man: reassure and send him home.

PMID- 25588733
TI  - Cytotoxic, antitumour-promoting and inhibition of protein denaturation effects of
      flavonoids, isolated from Potentilla evestita Th. Wolf.
AB  - This study was designed to evaluate the isolated flavonoids (chrysin 1, and
      umbelliferone 2) from Potentilla evestita for cytotoxic, antitumour-promoting and
      inhibition of protein denaturation activities. The results showed marked
      cytotoxic effect of compounds 1 and 2 in brine shrimp cytotoxic assay at various
      concentrations with LD50 of 34.5 and 31.8 mg/mL, respectively. In Epstein-Barr
      virus early antigen activation assay, both compounds 1 and 2 illustrated
      significant antitumour-promoting effect with IC50 values of 462 and 308 mol
      ratio/32 pmol TPA, respectively. The cytotoxic and antitumour-promoting effects
      of compounds were strongly supported by inhibition of protein denaturation
      activity with IC50 of 119 and 112 MUg/mL, respectively. In conclusion, both
      compounds possess strong cytotoxic, antitumour-promoting and inhibition of
      protein denaturation activities.

PMID- 25588731
TI  - Single-Limb Irradiation Induces Local and Systemic Bone Loss in a Murine Model.
AB  - Increased fracture risk is commonly reported in cancer patients receiving
      radiotherapy, particularly at sites within the field of treatment. The direct and
      systemic effects of ionizing radiation on bone at a therapeutic dose are not well
      characterized in clinically relevant animal models. Using 20-week-old male
      C57Bl/6 mice, effects of irradiation (right hindlimb; 2 Gy) on bone volume and
      microarchitecture were evaluated prospectively by microcomputed tomography and
      histomorphometry and compared to contralateral-shielded bone (left hindlimb) and
      non-irradiated control bone. One week postirradiation, trabecular bone volume
      declined in irradiated tibias (-22%; p < 0.0001) and femurs (-14%; p = 0.0586)
      and microarchitectural parameters were compromised. Trabecular bone volume
      declined in contralateral tibias (-17%; p = 0.003), and no loss was detected at
      the femur. Osteoclast number, apoptotic osteocyte number, and marrow adiposity
      were increased in irradiated bone relative to contralateral and non-irradiated
      bone, whereas osteoblast number was unchanged. Despite no change in osteoblast
      number 1 week postirradiation, dynamic bone formation indices revealed a
      reduction in mineralized bone surface and a concomitant increase in unmineralized
      osteoid surface area in irradiated bone relative to contralateral and non
      irradiated control bone. Further, dose-dependent and time-dependent calvarial
      culture and in vitro assays confirmed that calvarial osteoblasts and osteoblast
      like MC3T3 cells were relatively radioresistant, whereas calvarial osteocyte and
      osteocyte-like MLO-Y4 cell apoptosis was induced as early as 48 hours
      postirradiation (4 Gy). In osteoclastogenesis assays, radiation exposure (8 Gy)
      stimulated murine macrophage RAW264.7 cell differentiation, and coculture of
      irradiated RAW264.7 cells with MLO-Y4 or murine bone marrow cells enhanced this
      effect. These studies highlight the multifaceted nature of radiation-induced bone
      loss by demonstrating direct and systemic effects on bone and its many cell types
      using clinically relevant doses; they have important implications for bone health
      in patients treated with radiation therapy.

PMID- 25588734
TI  - Phloem as capacitor: radial transfer of water into xylem of tree stems occurs via
      symplastic transport in ray parenchyma.
AB  - The transfer of water from phloem into xylem is thought to mitigate increasing
      hydraulic tension in the vascular system of trees during the diel cycle of
      transpiration. Although a putative plant function, to date there is no direct
      evidence of such water transfer or the contributing pathways. Here, we trace the
      radial flow of water from the phloem into the xylem and investigate its diel
      variation. Introducing a fluorescent dye (0.1% [w/w] fluorescein) into the phloem
      water of the tree species Eucalyptus saligna allowed localization of the dye in
      phloem and xylem tissues using confocal laser scanning microscopy. Our results
      show that the majority of water transferred between the two tissues is
      facilitated via the symplast of horizontal ray parenchyma cells. The method also
      permitted assessment of the radial transfer of water during the diel cycle, where
      changes in water potential gradients between phloem and xylem determine the
      extent and direction of radial transfer. When injected during the morning, when
      xylem water potential rapidly declined, fluorescein was translocated, on average,
      farther into mature xylem (447 +/- 188 um) compared with nighttime, when xylem
      water potential was close to zero (155 +/- 42 um). These findings provide
      empirical evidence to support theoretical predictions of the role of phloem-xylem
      water transfer in the hydraulic functioning of plants. This method enables
      investigation of the role of phloem tissue as a dynamic capacitor for water
      storage and transfer and its contribution toward the maintenance of the
      functional integrity of xylem in trees.

PMID- 25588735
TI  - Phosphoenolpyruvate Carboxylase in Arabidopsis Leaves Plays a Crucial Role in
      Carbon and Nitrogen Metabolism.
AB  - Phosphoenolpyruvate carboxylase (PEPC) is a crucial enzyme that catalyzes an
      irreversible primary metabolic reaction in plants.Previous studies have used
      transgenic plants expressing ectopic PEPC forms with diminished feedback
      inhibition to examine the role of PEPC in carbon and nitrogen metabolism. To
      date, the in vivo role of PEPC in carbon and nitrogen metabolism has not been
      analyzed in plants. In this study, we examined the role of PEPC in plants,
      demonstrating that PPC1 and PPC2 were highly expressed genes encoding PEPC in
      Arabidopsis (Arabidopsis thaliana) leaves and that PPC1 and PPC2 accounted for
      approximately 93% of total PEPC activity in the leaves. A double mutant,
      ppc1/ppc2, was constructed that exhibited a severe growth-arrest phenotype. The
      ppc1/ppc2 mutant accumulated more starch and sucrose than wild-type plants when
      seedlings were grown under normal conditions. Physiological and metabolic
      analysis revealed that decreased PEPC activity in the ppc1/ppc2 mutant greatly
      reduced the synthesis of malate and citrate and severely suppressed ammonium
      assimilation. Furthermore, nitrate levels in the ppc1/ppc2 mutant were
      significantly lower than those in wild-type plants due to the suppression of
      ammonium assimilation. Interestingly, starch and sucrose accumulation could be
      prevented and nitrate levels could be maintained by supplying the ppc1/ppc2
      mutant with exogenous malate and glutamate, suggesting that low nitrogen status
      resulted in the alteration of carbon metabolism and prompted the accumulation of
      starch and sucrose in the ppc1/ppc2 mutant. Our results demonstrate that PEPC in
      leaves plays a crucial role in modulating the balance of carbon and nitrogen
      metabolism in Arabidopsis.

PMID- 25588736
TI  - Membrane-localized extra-large G proteins and Gbg of the heterotrimeric G
      proteins form functional complexes engaged in plant immunity in Arabidopsis.
AB  - In animals, heterotrimeric G proteins, comprising Ga, Gb, and Gg subunits, are
      molecular switches whose function tightly depends on Ga and Gbg interaction.
      Intriguingly, in Arabidopsis (Arabidopsis thaliana), multiple defense responses
      involve Gbg, but not Ga. We report here that the Gbg dimer directly partners with
      extra-large G proteins (XLGs) to mediate plant immunity. Arabidopsis mutants
      deficient in XLGs, Gb, and Gg are similarly compromised in several pathogen
      defense responses, including disease development and production of reactive
      oxygen species. Genetic analysis of double, triple, and quadruple mutants
      confirmed that XLGs and Gbg functionally interact in the same defense signaling
      pathways. In addition, mutations in XLG2 suppressed the seedling lethal and cell
      death phenotypes of BRASSINOSTEROID INSENSITIVE1-associated receptor kinase1
      interacting receptor-like kinase1 mutants in an identical way as reported for
      Arabidopsis Gb-deficient mutants. Yeast (Saccharomyces cerevisiae) three-hybrid
      and bimolecular fluorescent complementation assays revealed that XLG2 physically
      interacts with all three possible Gbg dimers at the plasma membrane. Phylogenetic
      analysis indicated a close relationship between XLGs and plant Ga subunits,
      placing the divergence point at the dawn of land plant evolution. Based on these
      findings, we conclude that XLGs form functional complexes with Gbg dimers,
      although the mechanism of action of these complexes, including
      activation/deactivation, must be radically different form the one used by the
      canonical Ga subunit and are not likely to share the same receptors. Accordingly,
      XLGs expand the repertoire of heterotrimeric G proteins in plants and reveal a
      higher level of diversity in heterotrimeric G protein signaling.

PMID- 25588737
TI  - Characterization of chloroplast protein import without Tic56, a component of the
      1-megadalton translocon at the inner envelope membrane of chloroplasts.
AB  - We report on the characterization of Tic56, a unique component of the recently
      identified 1-MD translocon at the inner envelope membrane of chloroplasts (TIC)
      in Arabidopsis (Arabidopsis thaliana) comprising Tic20, Tic100, and Tic214. We
      isolated Tic56 by copurification with Tandem Affinity Purification-tagged Toc159
      in the absence of precursor protein, indicating spontaneous and translocation
      independent formation of the translocon at the outer envelope membrane of
      chloroplasts (TOC) and TIC supercomplexes. Tic56 mutant plants have an albino
      phenotype and are unable to grow without an external carbon source. Using
      specific enrichment of protein amino termini, we analyzed the tic56-1 and plastid
      protein import2 (toc159) mutants to assess the in vivo import capacity of
      plastids in mutants of an outer and inner envelope component of the anticipated
      TOC-TIC supercomplex. Inboth mutants, we observed processing of several import
      substrates belonging to various pathways. Our results suggest that despite the
      severe developmental defects, protein import into Tic56-deficient plastids is
      functional to a considerable degree, indicating the existence of alternative
      translocases at the inner envelope membrane.

PMID- 25588738
TI  - Comparison of mercury bioaccumulation between wild and mariculture food chains
      from a subtropical bay of Southern China.
AB  - Bioaccumulation and trophic transfer of mercury (Hg) both in the natural marine
      ecosystem and the mariculture ecosystem were studied at Daya Bay, a subtropical
      bay in Southern China. Averaged Hg concentrations in sediment, phytoplankton,
      macrophyte, shrimp, crab, shellfish, planktivorous fish, carnivorous fish, farmed
      pompano, farmed snapper, compound feed and trash fish were 0.074, 0.054, 0.044,
      0.098, 0.116, 0.171, 0.088, 0.121, 0.210, 0.125, 0.038 and 0.106 MUg g(-1) dw,
      respectively. These Hg levels were at the low-middle ends of the global range.
      Positive correlation between Hg concentrations in farmed fish and fish
      weights/sizes was observed, whereas no clear correlation between Hg
      concentrations and lipid contents was found. Hg concentrations followed
      macrophyte < phytoplankton < sediment < planktivorous fish < shrimp < crab <
      carnivorous fish < shellfish, and commercial feed < trash fish < farmed fish. Hg
      was biomagnified along the marine food chain in the ecosystem of Daya Bay. Hg
      levels in the farmed fish were higher than those in the wild fish primarily
      because of the higher Hg level in fish feed and the smaller size of marine wild
      fish. 

PMID- 25588739
TI  - Evaluation of in vivo antitumor effects of ANT2 shRNA delivered using PEI and
      ultrasound with microbubbles.
AB  - Gene therapy using RNA interference can be directed against tumors through
      various strategies, but has been hindered owing to the inefficiency of non-viral
      delivery. To evaluate the antitumor effects of adenine nucleotide translocase-2
      (ANT2) short hairpin RNA (shRNA) by intraperitoneal injection using the
      polyethylenimine (PEI) and an ultrasound gene delivery method, human breast
      carcinoma MDA-MB-231 cells were injected subcutaneously into NOG (NOD/Shi-scid/IL
      2Rgamma(null)) mice. The results showed greater tumor regression (*P<0.05) as
      well as an increased survival rate in the group receiving ANT2 shRNA+two types of
      enhancer relative to the groups receiving ANT2 shRNA without enhancer. These
      findings demonstrate that the introduction of PEI and ultrasound with SonoVue
      exerted enhanced antitumor effects in vivo. Although the combination of jet-PEI
      and ultrasound provided the best results with respect to tumor regression, the
      antitumor effects from the individual enhancers were approximately equivalent. In
      addition, we confirmed that there was no toxicity on aspartate aminotransferase
      and alanine aminotransferase levels in the liver and albumin, blood urea nitrogen
      or creatine kinase levels in the kidney following the various gene delivery
      methods. 

PMID- 25588740
TI  - Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in
      adult and neonate rats.
AB  - Intracerebral administration of recombinant adeno-associated vector (AAV) has
      been performed in several clinical trials. However, delivery into the brain
      requires multiple injections and is not efficient to target the spinal cord, thus
      limiting its applications. To assess widespread and less invasive strategies, we
      tested intravenous (IV) or intrathecal (that is, in the cerebrospinal fluid
      (CSF)) delivery of a rAAVrh10-egfp vector in adult and neonate rats and studied
      the effect of the age at injection on neurotropism. IV delivery is more efficient
      in neonates and targets predominantly Purkinje cells of the cerebellum and
      sensory neurons of the spinal cord and dorsal root ganglia. A single intra-CSF
      administration of AAVrh10, single strand or oversized self-complementary, is
      efficient for the targeting of neurons in the cerebral hemispheres, cerebellum,
      brainstem and spinal cord. Green fluorescent protein (GFP) expression is more
      widespread in neonates when compared with adults. More than 50% of motor neurons
      express GFP in the three segments of the spinal cord in neonates and in the
      cervical and thoracic regions in adults. Neurons are almost exclusively
      transduced in neonates, whereas neurons, astrocytes and rare oligodendrocytes are
      targeted in adults. These results expand the possible routes of delivery of
      AAVrh10, a serotype that has shown efficacy and safety in clinical trials
      concerning neurodegenerative diseases. 

PMID- 25588742
TI  - Preferable sites and orientations of transgene inserted in the adenovirus vector
      genome: The E3 site may be unfavorable for transgene position.
AB  - The adenovirus vector (AdV) can carry two transgenes in its genome, the
      therapeutic gene and a reporter gene, for example. The E3 insertion site has
      often been used for the expression of the second transgene. A transgene can be
      inserted at six different sites/orientations: E1, E3 and E4 sites, and right and
      left orientations. However, the best combination of the insertion sites and
      orientations as for the titers and the expression levels has not sufficiently
      been studied. We attempted to construct 18 AdVs producing GFP or LacZ gene driven
      by the EF1alpha promoter and Cre gene driven by the alpha-fetoprotein promoter.
      The AdV containing GFP gene at E3 in the rightward orientation (GFP-E3R) was not
      available. The LacZ-E3R AdV showed 20-fold lower titer and 50-fold lower level of
      fiber mRNA than the control E1L AdV. Notably, we found four aberrantly spliced
      mRNAs in the LacZ-E3L/R AdVs, probably explaining their very low titers. Although
      the transgene expression levels in the E4R AdVs were about threefold lower than
      those in the E1L AdVs, their titers are comparable with that of E1L AdVs. We
      concluded that E1L and E4R sites/orientations are preferable for expressing the
      main target gene and a second gene, respectively. 

PMID- 25588741
TI  - Potent antitumor activity of Oct4 and hypoxia dual-regulated oncolytic adenovirus
      against bladder cancer.
AB  - Most solid tumors undergo hypoxia, leading to rapid cell division, metastasis and
      expansion of a cell population with hallmarks of cancer stem cells (CSCs). Tumor
      selective replication of oncolytic adenoviruses may be hindered by oxygen
      deprivation in tumors. It is desirable to develop a potent oncolytic adenovirus,
      retaining its antitumor activity even in a hypoxic environment. We have
      previously generated an Oct4-dependent oncolytic adenovirus, namely Ad9OC, driven
      by nine copies of the Oct4 response element (ORE) for specifically killing Oct4
      overexpressing bladder tumors. Here, we developed a novel Oct4 and hypoxia dual
      regulated oncolytic adenovirus, designated AdLCY, driven by both hypoxia response
      element (HRE) and ORE. We showed that hypoxia-inducible factor (HIF)-2alpha and
      Oct4 were frequently overexpressed in hypoxic bladder cancer cells, and HIF
      2alpha was involved in HRE-dependent and Oct4 transactivation. AdLCY exhibited
      higher cytolytic activities than Ad9OC against hypoxic bladder cancer cells,
      while sparing normal cells. AdLCY exerted potent antitumor effects in mice
      bearing human bladder tumor xenografts and syngeneic bladder tumors. It could
      target hypoxic CD44- and CD133-positive bladder tumor cells. Therefore, AdLCY may
      have therapeutic potential for targeting hypoxic bladder tumors and CSCs. As Oct4
      is expressed in various cancers, AdLCY may be further explored as a broad
      spectrum anticancer agent. 

PMID- 25588743
TI  - Replicating reoviruses with a transgene replacing the codons for the head domain
      of the viral spike.
AB  - The capacity to modify the reovirus genome facilitates generation of new
      therapeutic reoviruses. We describe a method for generating replication-competent
      reoviruses carrying a heterologous transgene. The strategy is based on the
      expanded-tropism reovirus mutant jin-3, which can infect cells independent of the
      reovirus receptor junction-adhesion molecule A (JAM-A). Jin-3 harbors a mutation
      in the S1 segment, resulting in a G196R substitution in the tail of the spike
      protein sigma1. The use of the jin-3 tail-encoding S1 segment allows replacing
      the codons for the JAM-A-binding head domain by up to 522  nucleotides of foreign
      sequences, without exceeding the size of the wild-type S1 segment. We inserted
      the codons for the porcine teschovirus-1 2A element fused with those encoding the
      fluorescent protein iLOV. Replicating rS1His-2A-iLOV reoviruses were generated by
      co-transfection of expression plasmids for all reovirus segments. These
      reoviruses contain the S1His-2A-iLOV segment in the absence of the wild-type S1
      segment. Density-gradient centrifugation confirmed the association of the sigma1
      tail fragment with the capsid. Both JAM-A-positive and -negative cells exposed to
      the rS1His-2A-iLOV reoviruses exhibited iLOV fluorescence, confirming the jin-3
      derived expanded-tropism phenotype. These data demonstrated the feasibility of
      generating decapitated replication-competent T3D reoviruses carrying a
      heterologous transgene. 

PMID- 25588744
TI  - Sendai virus-mediated gene transfer of the c-myc suppressor far-upstream element
      binding protein-interacting repressor suppresses head and neck cancer.
AB  - Far-upstream element-binding protein-interacting repressor (FIR) is a
      transcription factor that inhibits c-Myc expression and has been shown to have
      antitumor effects in some malignancies. Here, we evaluated the antitumor effects
      of FIR using fusion gene-deleted Sendai virus (SeV/DeltaF) as a nontransmissible
      vector against head and neck squamous cell carcinoma (HNSCC). Using in vitro and
      in vivo xenograft mouse models, we observed efficient expression of green
      fluorescent protein (GFP) following transduction with the SeV/DeltaF vector
      encoding GFP (GFP-SeV/DeltaF) into HNSCC cells. In vitro and in vivo studies
      revealed that administration of the FIR-encoded SeV/DeltaF (FIR-SeV/DeltaF)
      vector exerted significant antitumor effects, suppressed c-Myc expression and
      induced apoptosis in HNSCC. Additionally, the antitumor effects of FIR or the
      expression of GFP following administration of the FIR- or GFP-SeV/DeltaF vector,
      respectively, were dependent on the multiplicity of infection or titer.
      Furthermore, the SeV/DeltaF vector itself had no cytotoxic effects. Therefore,
      the SeV/DeltaF vector may be safe and useful for the treatment of HNSCC, allowing
      for high-titer SeV/DeltaF vector administration for anticancer gene therapy. In
      addition, SeV/DeltaF vector-mediated FIR gene therapy demonstrated effective
      tumor suppression in HNSCC, suggesting that this therapy may have the potential
      for clinical use as a novel strategy for HNSCC treatment. 

PMID- 25588747
TI  - Spontaneous fractures in custom-made porous hydroxyapatite cranioplasty implants:
      is fragility the only culprit?
AB  - BACKGROUND: Although the porous hydroxyapatite (PHA) used in custom-made
      cranioplasty implants is a material appreciated for its biomimetic properties,
      before osteointegration it is initially very fragile. Nevertheless, we wondered
      whether this primary fragility is entirely due to brittleness or whether the
      surgeon's actions may influence the behavior of the material. METHODS: To study
      the influence of the surgeon's behavior, we made a virtual model of a custom-made
      PHA cranioplasty implant and submitted it to three implant procedural variables
      using finite element methods. In the first test, a scenario in which the
      surgeon's design, validation, and positioning techniques are impeccable, the
      edges of the implant adhered well to the craniectomy margins. In the second test,
      a discrepancy between a portion of the perimeter of the craniectomy and the
      profile of the prosthesis was modeled, and in the third test, several gaps were
      simulated between the implant and the craniectomy margins. RESULTS: Our
      mathematical model showed that when local and general discontinuities were
      included in the test scenarios, there was an increase in the load coming to bear
      on the cranioplasty implant, which amounted to 80 and 50 %, respectively.
      CONCLUSIONS: The fragility of custom-made PHA cranioplasty implants increases if
      the surgeon fails to achieve a precise design and validation, and/or an accurate
      surgical procedure. Nevertheless, careful attention during these phases helps to
      maintain the strength of the implant, given the more favorable mechanical
      conditions, without interfering with its biomimetic capacity.

PMID- 25588745
TI  - Functional characterization and developmental expression profiling of gibberellin
      signalling components in Vitis vinifera.
AB  - Gibberellins (GAs) regulate numerous developmental processes in grapevine (Vitis
      vinifera) such as rachis elongation, fruit set, and fruitlet abscission. The
      ability of GA to promote berry enlargement has led to its indispensable use in
      the sternospermocarpic ('seedless') table grape industry worldwide. However,
      apart from VvGAI1 (VvDELLA1), which regulates internode elongation and
      fruitfulness, but not berry size of seeded cultivars, little was known about GA
      signalling in grapevine. We have identified and characterized two additional
      DELLAs (VvDELLA2 and VvDELLA3), two GA receptors (VvGID1a and VvGID1b), and two
      GA-specific F-box proteins (VvSLY1a and VvSLY1b), in cv. Thompson seedless. With
      the exception of VvDELLA3-VvGID1b, all VvDELLAs interacted with the VvGID1s in a
      GA-dependent manner in yeast two-hybrid assays. Additionally, expression of these
      grape genes in corresponding Arabidopsis mutants confirmed their functions in
      planta. Spatiotemporal analysis of VvDELLAs showed that both VvDELLA1 and
      VvDELLA2 are abundant in most tissues, except in developing fruit where VvDELLA2
      is uniquely expressed at high levels, suggesting a key role in fruit development.
      Our results further suggest that differential organ responses to exogenous GA
      depend on the levels of VvDELLA proteins and endogenous bioactive GAs.
      Understanding this interaction will allow better manipulation of GA signalling in
      grapevine. 

PMID- 25588748
TI  - Peroneal intraneural ganglion cysts at the fibular neck: the layered "U" surgical
      approach to the articular branch and superior tibiofibular joint.
AB  - BACKGROUND: Intraneural ganglia most commonly occur within the peroneal nerve
      near the fibular neck. Disconnection of the articular branch is required in their
      treatment. Surgical intervention can be challenging because of unfamiliarity with
      the region or scarring from previous surgery. METHOD: We present the layered "U"
      technique for peroneal intraneural ganglia with clinical examples. Dissection is
      carried down in parallel to the U-shaped course of the articular branch to
      provide optimal visualization and avoid injury to major branches of the nerve.
      CONCLUSION: This pathoanatomic approach provides direct and safe exposure of the
      articular branch of the common peroneal nerve.

PMID- 25588746
TI  - The role of minimally invasive surgery in pediatric solid tumors.
AB  - During recent years, minimally invasive surgery (MIS) has become the standard
      approach for various operations in infants and children. MIS in pediatric
      thoracic and abdominal tumors is a controversial approach in the surgical
      management of childhood cancer. Meanwhile, more and more oncological biopsies and
      resections are being performed laparoscopically or thoracoscopically. Despite its
      increasing role in pediatric tumor surgery, the different national and
      international multicenter trial groups have not yet implemented MIS within
      guidelines and recommendations in most of the current treatment protocols. An
      increasing number of retrospective reports describes a potential role of MIS in
      the management of different pediatric oncological entities. Over the time, there
      has been a diverse development of this approach with regard to the different
      neoplasms. Nevertheless, there is a lack of prospective randomized trails
      assessing MIS. This still represents a requirement for evidence-based medicine
      and judging the advantages and disadvantages of this approach. The purpose of
      this state-of-the-art article is to review the current literature to describe the
      application of MIS in pediatric solid tumors. 

PMID- 25588749
TI  - Complications of cranioplasty using a bone flap sterilised by autoclaving
      following decompressive craniectomy.
AB  - BACKGROUND: Increasing use of decompressive craniectomies has led to a
      corresponding number of cranioplasties performed to replace the subsequent bone
      defect created. We aimed to evaluate the morbidity associated with cranioplasty
      using an autologous bone flap sterilised in an autoclave. METHODS: We
      retrospectively analysed data from 149 patients who underwent cranioplasty
      following decompressive craniectomy during the time period January 1998 to
      December 2012. Autologous bone flaps were sterilised in an autoclave and stored
      in a refrigerator at a temperature of 8 degrees above zero until cranioplasty was
      performed. Complications were registered and patient data were analysed in order
      to identify risk factors for surgical site infection and bone flap resorption
      after cranioplasty. Only the patients with a follow-up period of >24 months were
      included in the analysis of bone flap resorption (110 patients). RESULTS:
      Surgical side infection occurred in only five patients (3.3%), whereas bone flap
      resorption developed in 22 patients (20%). The multivariate analysis of the
      presented data identified the operating time of >120 min (p = 0.0277; OR, 16.877;
      95% CI, 1.364-208.906) and the presence of diabetes mellitus (p = 0.0016; OR,
      54.261; 95% CI, 4.529-650.083) as independent risk factors of development of
      infection and the presence of ventriculo-peritoneal (VP) shunt (p < 0.0001; OR,
      35.564; 95% CI, 9.962-126.960) as independent risk factor of development of the
      bone flap resorption. CONCLUSIONS: Reimplantation of the autoclaved autologous
      bone flap following decompressive craniectomy is a simple and cheep alternative
      to other techniques and is available to any institution that provides autoclaving
      sterilisation services. This method is associated with a low rate of surgical
      site infection, but with a significant rate of the bone flap resorption.

PMID- 25588750
TI  - Authors' reply to letter to the editor regarding "coincident pituitary adenoma
      and sellar meningioma".

PMID- 25588751
TI  - Spinal cord injury induced neuropathic pain: Molecular targets and therapeutic
      approaches.
AB  - Neuropathic pain, especially that resulting from spinal cord injury, is a
      tremendous clinical challenge. A myriad of biological changes have been
      implicated in producing these pain states including cellular interactions,
      extracellular proteins, ion channel expression, and epigenetic influences.
      Physiological consequences of these changes are varied and include functional
      deficits and pain responses. Developing therapies that effectively address the
      cause of these symptoms require a deeper knowledge of alterations in the
      molecular pathways. Matrix metalloproteinases and tissue inhibitors of
      metalloproteinases are two promising therapeutic targets. Matrix
      metalloproteinases interact with and influence many of the studied pain pathways.
      Gene expression of ion channels and inflammatory mediators clearly contributes to
      neuropathic pain. Localized and time dependent targeting of these proteins could
      alleviate and even prevent neuropathic pain from developing. Current therapeutic
      options for neuropathic pain are limited primarily to analgesics targeting the
      opioid pathway. Therapies directed at molecular targets are highly desirable and
      in early stages of development. These include transplantation of exogenously
      engineered cell populations and targeted gene manipulation. This review describes
      specific molecular targets amenable to therapeutic intervention using currently
      available delivery systems. 

PMID- 25588752
TI  - Predicting the survival probability of gastric cancer patients developing
      metastatic epidural spinal cord compression (MESCC).
AB  - To create a tool for estimating the survival of gastric cancer patients
      developing MESCC, clinical factors were evaluated in 29 patients. Factors were
      age, gender, performance status, affected vertebrae, ambulatory status, further
      bone metastases, visceral metastases, time from gastric cancer diagnosis until
      MESCC and rapidity of developing weakness of legs. On multivariate analyses,
      visceral metastases (risk ratio: 6.80; p = 0.003) and rapidity of weakening of
      legs (risk ratio: 2.73; p = 0.023) had a significant effect on survival and were
      included in the tool. Scoring points for each of the two factors were either 0 or
      1, depending on the 6-month survival rates. According to the sum of the points,
      three groups were built: 0 points (n = 12), 1 point (n = 10) and 2 points (n =
      7). Six-month survival rates were 0, 20 and 100 % (p < 0.001). This tool for
      patients with MESCC from gastric cancer estimates survival probabilities, which
      is important for tailoring treatment to patients' needs.

PMID- 25588754
TI  - The vulnerability of rules in complex work environments: dynamism and uncertainty
      pose problems for cognition.
AB  - Many complex work environments rely heavily on cognitive operators using rules.
      Operators sometimes fail to implement rules, with catastrophic human, social and
      economic costs. Rule-based error is widely reported, yet the mechanisms of rule
      vulnerability have received less attention. This paper examines rule
      vulnerability in the complex setting of airline transport operations. We examined
      'the stable approach criteria rule', which acts as a system defence during the
      approach to land. The study experimentally tested whether system state complexity
      influenced rule failure. The results showed increased uncertainty and dynamism
      led to increased likelihood of rule failure. There was also an interaction
      effect, indicating complexity from different sources can combine to further
      constrain rule-based response. We discuss the results in relation to recent
      aircraft accidents and suggest that 'rule-based error' could be progressed to
      embrace rule vulnerability, fragility and failure. This better reflects the
      influence that system behaviour and cognitive variety have on rule-based
      response. Practitioner Summary: In this study, we examined mechanisms of rule
      vulnerability in the complex setting of airline transport operations. The results
      suggest work scenarios featuring high uncertainty and dynamism constrain rule
      based response, leading to rules becoming vulnerable, fragile or failing
      completely. This has significant implications for rule-intensive, safety critical
      work environments. 

PMID- 25588753
TI  - Translational horizons in the tumor microenvironment: harnessing breakthroughs
      and targeting cures.
AB  - Chemotherapy and targeted therapy have opened new avenues in clinical oncology.
      However, there is a lack of response in a substantial percentage of cancer
      patients and diseases frequently relapse in those who even initially respond.
      Resistance is, at present, the major barrier to conquering cancer, the most
      lethal age-related pathology. Identification of mechanisms underlying resistance
      and development of effective strategies to circumvent treatment pitfalls thereby
      improving clinical outcomes remain overarching tasks for scientists and
      clinicians. Growing bodies of data indicate that stromal cells within the
      genetically stable but metabolically dynamic tumor microenvironment confer
      acquired resistance against anticancer therapies. Further, treatment itself
      activates the microenvironment by damaging a large population of benign cells,
      which can drastically exacerbate disease conditions in a cell nonautonomous
      manner, and such off-target effects should be well taken into account when
      establishing future therapeutic rationale. In this review, we highlight relevant
      biological mechanisms through which the tumor microenvironment drives development
      of resistance. We discuss some unsolved issues related to the preclinical and
      clinical trial paradigms that need to be carefully devised, and provide
      implications for personalized medicine. In the long run, an insightful and
      accurate understanding of the intricate signaling networks of the tumor
      microenvironment in pathological settings will guide the design of new clinical
      interventions particularly combinatorial therapies, and it might help overcome,
      or at least prevent, the onset of acquired resistance. 

PMID- 25588755
TI  - Oxidative stress: a concept in redox biology and medicine.
AB  - "Oxidative stress" as a concept in redox biology and medicine has been formulated
      in 1985; at the beginning of 2015, approx. 138,000 PubMed entries show for this
      term. This concept has its merits and its pitfalls. Among the merits is the
      notion, elicited by the combined two terms of (i) aerobic metabolism as a steady
      state redox balance and (ii) the associated potential strains in the balance as
      denoted by the term, stress, evoking biological stress responses. Current
      research on molecular redox switches governing oxidative stress responses is in
      full bloom. The fundamental importance of linking redox shifts to
      phosphorylation/dephosphorylation signaling is being more fully appreciated,
      thanks to major advances in methodology. Among the pitfalls is the fact that the
      underlying molecular details are to be worked out in each particular case, which
      is bvious for a global concept, but which is sometimes overlooked. This can lead
      to indiscriminate use of the term, oxidative stress, without clear relation to
      redox chemistry. The major role in antioxidant defense is fulfilled by
      antioxidant enzymes, not by small-molecule antioxidant compounds. The field of
      oxidative stress research embraces chemistry, biochemistry, cell biology,
      physiology and pathophysiology, all the way to medicine and health and disease
      research. 

PMID- 25588756
TI  - Understanding the basics of posterior tibial tendon dysfunction and the
      associated flatfoot: conservative and surgical thoughts.

PMID- 25588758
TI  - How much is too much breast screening?

PMID- 25588757
TI  - Pulmonary vein isolation for atrial fibrillation in the postpneumonectomy
      population: a feasibility, safety, and outcomes study.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) of the remnant pulmonary vein (PV)
      stumps in pneumonectomy patients has not been well characterized. METHODS: This
      is a multicenter observational study of patients with a remnant PV stump after
      pneumonectomy. Consecutive patients with a history of pneumonectomy and who had
      undergone RF ablation for drug refractory AF were identified from the AF database
      at the participating institutions. RESULTS: There were 15 patients in whom
      pneumonectomy was performed, for resection of tumors in 10, infection in 4, and
      bullae in 1 patient and who underwent RF ablation for AF. The mean age was 63 +/-
      7 years. The stumps were from the right lower PV in 5, left upper PV in 5, left
      lower PV in 3, and right upper PV in 2 patients. All the PV stumps were
      electrically active with PV potentials and 9 (60%) of them had triggered
      activity. PVI was performed in 14 and focal isolation in 1 patient. At 1-year
      follow-up, 80% were free of AF, off of antiarrhythmic medications. CONCLUSION: PV
      stumps in AF patients with previous pneumonectomy are electrically active and are
      frequently the sites of active firing. Isolation of these PV stumps can be
      accomplished safely and effectively using catheter ablation with no practical
      concern for PV stenosis or compromising PV stump integrity.

PMID- 25588759
TI  - Concluding remarks: summary of some of our recent studies in the field of
      conjugating plasmonic gold nanoparticles to single cancer cells and their
      molecular and cellular dynamics.
AB  - This Faraday meeting was indeed very educational and important. We should all
      thank the organizing committee, and especially our Chair, Professor Nguyen TK
      Thanh, for a job well done. The Faraday Discussion format is certainly very
      creative and effective. Getting each presenter of one of the excellent posters to
      summarize the topic of their poster in five minutes was very important in
      encouraging the delegates to spend their time in the poster sessions with the
      speakers working on research that overlapped with his or her own. 

PMID- 25588762
TI  - Recirculation during veno-venous extra-corporeal membrane oxygenation--a
      simulation study.
AB  - PURPOSE: Veno-venous ECMO is indicated in reversible life-threatening respiratory
      failure without life-threatening circulatory failure. Recirculation of oxygenated
      blood in the ECMO circuit decreases efficiency of patient oxygen delivery but is
      difficult to measure. We seek to identify and quantify some of the factors
      responsible for recirculation in a simulation model and compare with clinical
      data. METHODS: A closed-loop real-time simulation model of the cardiovascular
      system has been developed. ECMO is simulated with a fixed flow pump 0 to 5 l/min
      with various cannulation sites - 1) right atrium to inferior vena cava, 2)
      inferior vena cava to right atrium, and 3) superior+inferior vena cava to right
      atrium. Simulations are compared to data from a retrospective cohort of 11
      consecutive adult veno-venous ECMO patients in our department. RESULTS:
      Recirculation increases with increasing ECMO-flow, decreases with increasing
      cardiac output, and is highly dependent on choice of cannulation sites. A more
      peripheral drainage site decreases recirculation substantially. CONCLUSIONS:
      Simulations suggest that recirculation is a significant clinical problem in veno
      venous ECMO in agreement with clinical data. Due to the difficulties in measuring
      recirculation and interpretation of the venous oxygen saturation in the ECMO
      drainage blood, flow settings and cannula positioning should rather be optimized
      with help of arterial oxygenation parameters. Simulation may be useful in
      quantification and understanding of recirculation in VV-ECMO.

PMID- 25588761
TI  - Current roles of endoscopy in the management of intraductal papillary mucinous
      neoplasm of the pancreas.
AB  - Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized
      by intraductal papillary proliferation of mucin-producing epithelial cells that
      exhibit various degrees of dysplasia. IPMN is classified into four histological
      subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) according to its
      histomorphological and immunohistochemical characteristics. Endoscopic retrograde
      cholangiopancreatography plays a crucial role in the evaluation of these features
      of IPMN. Endoscopic ultrasonography (EUS) has proven to be more sensitive than
      computed tomography or magnetic resonance imaging for early detection of
      malignancy. The present review addresses the current roles of endoscopy and
      related techniques in the management of IPMN. The particular focus is on
      diagnosing IPMN and malignancy within IPMN, detecting pancreatic cancer
      concomitant with IPMN, differentiating the epithelial subtypes of IPMN,
      determining the optimal strategy for the management of branch duct IPMN, and
      discussing innovative endoscopic technology related to IPMN. The disadvantages of
      endoscopic examinations of IPMN and different attitudes toward EUS-guided fine
      needle aspiration for IPMN between Japan (negative) and other countries (active)
      are also discussed. 

PMID- 25588763
TI  - Pre-clinical evaluation of an adult extracorporeal carbon dioxide removal system
      with active mixing for pediatric respiratory support.
AB  - The objective of this work was to conduct pre-clinical feasibility studies to
      determine if a highly efficient, active-mixing, adult extracorporeal carbon
      dioxide removal (ECCO2R) system can safely be translated to the pediatric
      population. The Hemolung Respiratory Assist System (RAS) was tested in vitro and
      in vivo to evaluate its performance for pediatric veno-venous applications. The
      Hemolung RAS operates at blood flows of 350-550 ml/min and utilizes an integrated
      pump-gas exchange cartridge with a membrane surface area of 0.59 m2 as the only
      component of the extracorporeal circuit. Both acute and seven-day chronic in vivo
      tests were conducted in healthy juvenile sheep using a veno-venous cannulation
      strategy adapted to the in vivo model. The Hemolung RAS was found to have gas
      exchange and pumping capabilities relevant to patients weighing 3-25 kg. Seven
      day animal studies in juvenile sheep demonstrated that veno-venous extracorporeal
      support could be used safely and effectively with no significant adverse
      reactions related to device operation.

PMID- 25588764
TI  - On the roughness measurement on knee prostheses.
AB  - The majority of total knee replacements currently implanted present an
      articulation composed of two metal parts, femoral and tibial components, between
      which there is a polyethylene insert serving as a bearing surface. The finishing
      surface of the metal components is a very important factor in minimizing the
      polyethylene wear rate and, later, the gradual production of metal and plastic
      debris. Considering the role of surface roughness on volumetric wear rates, the
      purpose of this study is to develop a protocol for the roughness characterization
      of total knee prosthesis (TKP) metal components, taking into consideration a
      limited number of points on each surface. Six mobile TKP of different sizes
      (three size 2 and three size 6) were tested on a knee joint simulator to compare
      the wear behavior of each group. After 2 million cycles the weight loss by the
      polyethylene inserts was measured with gravimetric method and the surface
      roughness of the metallic components was assessed in terms of average surface
      roughness, Ra, skewness, Rsk, and total roughness, Rt. Roughness measurement
      involved 29 points on each femoral condyle and 26 points on each metal tibial
      plate. The data collected has shown an increased roughness upon wear testing for
      both the investigated TKP sizes. No statistical differences were observed between
      the two groups for both the parameters Ra, Rsk, and Rt. The surface of all
      metallic components became more negatively skewed, indicating diminishing peaks.
      The various parameters were correlated to the volumetric loss using a linear
      regression analysis. 

PMID- 25588765
TI  - Low-flow veno-venous extracorporeal CO2 removal: first clinical experience in
      lung transplant recipients.
AB  - BACKGROUND: Low-flow extracorporeal CO2 removal devices are easy to setup and
      manage and may provide valuable ventilation support. METHODS: We employed a new
      device (ProLUNG) recently introduced into the clinical arsenal that exploits a
      simple hemoperfusion technique sustained by blood flows lower than 500 ml/min to
      remove CO2 from the venous blood. It was used as an adjunctive support to
      mechanical ventilation during and after four lung transplantations in our center.
      RESULTS: Two patients with cystic fibrosis, one with pulmonary fibrosis, and one
      with emphysema were included. They underwent lung transplantation and presented
      hypercapnia and respiratory acidosis before, during, or after the surgical
      procedure. After 1 h of treatment with the ProLUNG circuit, all patients showed
      reduced CO2 levels and increased pH; these variables remained stable until the
      end of treatment. CONCLUSIONS: Our data suggest that this new device is effective
      in removing CO2 and stabilizing the pH.

PMID- 25588766
TI  - Feasibility of a priori numerical assessment of plaque scaffolding after carotid
      artery stenting in clinical routine: proof of concept.
AB  - PURPOSE: Carotid artery stenting (CAS) is an alternative procedure for the
      treatment of severely stenosed carotid artery lesions in high-risk patients.
      Appropriate patient selection and stent design are paramount to achieve a low
      stroke and death rate in these complex high-risk procedures. This study
      introduces and evaluates a novel virtual, patient-specific, pre-operative
      environment to quantify scaffolding parameters based on routine imaging
      techniques. METHODS: Two patients who underwent CAS with two different sizes of
      the Acculink stent (Abbott Vascular, Santa Clara, CA, USA) were studied. Pre
      operative data were used to build the numerical models for the virtual procedure.
      Numerical results were validated with post-operative angiography. Using novel
      virtual geometrical tools, incomplete stent apposition, free cell area and
      largest fitting sphere in the stent cell were evaluated in situ as quantitative
      measures of successful stent placement and to assess potential risk factors for
      CAS complications. RESULTS: A quantitative validation of the numerical outcome
      with post-operative images noted differences in lumen diameter of 5.31 +/- 8.05%
      and 4.12 +/- 9.84%, demonstrating the reliability of the proposed methodology.
      The quantitative measurements of the scaffolding parameters on the virtually
      deployed stent geometry highlight the variability of the device behavior in
      relation to the target lesion. The free cell area depends on the target diameter
      and oversizing, while the largest fitting spheres and apposition values are
      influenced by the local concavity and convexity of the vessel. CONCLUSIONS: The
      proposed virtual environment may be an additional tool for endovascular
      specialists especially in complex anatomical cases where stent design and
      positioning may have a higher impact on procedural success and outcome.

PMID- 25588767
TI  - Preliminary evidence of the effects of high-frequency repetitive transcranial
      magnetic stimulation (rTMS) on swallowing functions in post-stroke individuals
      with chronic dysphagia.
AB  - BACKGROUND: There is growing evidence of potential benefits of repetitive
      transcranial magnetic stimulation (rTMS) in the rehabilitation of dysphagia.
      However, the site and frequency of stimulation for optimal effects are not clear.
      AIMS: The aim of this pilot study is to investigate the short-term effects of
      high-frequency 5 Hz rTMS applied to the tongue region of the motor cortex on
      swallowing functions and the quality of life of post-stroke individuals with
      dysphagia. METHODS & PROCEDURES: Two male and two female participants were
      assigned randomly to active and sham groups. The participants in the active group
      received 10 sessions of active rTMS for 2 weeks, whereas the sham participants
      received 10 sessions of sham rTMS for 2 weeks. Each participant received a total
      of 3000 pulses of 5 Hz active or sham rTMS per day for 10 days. Outcome measures
      were taken at baseline, 1 week and 1 month post-rTMS. OUTCOMES & RESULTS:
      Participants who received active rTMS had improved swallowing functions and
      swallowing-related quality of life at 1 week and 1 month post-stimulation.
      CONCLUSIONS & IMPLICATIONS: The study showed that excitatory rTMS applied over
      the tongue motor cortex is a feasible approach in individuals with chronic post
      stroke dysphagia. Further investigation with larger sample population is
      warranted to support the benefit of this stimulation protocol.

PMID- 25588769
TI  - NHS England pulls funding from 25 cancer treatments.

PMID- 25588768
TI  - The combined effects of alcohol consumption and body mass index on hepatic
      steatosis in a general population sample of European men and women.
AB  - BACKGROUND: Research on the association between alcohol consumption and hepatic
      steatosis revealed conflictive results. AIM: To investigate the associations
      between average daily alcohol consumption and binge drinking with hepatic
      steatosis, and to analyse combined effects of average daily alcohol consumption
      and binge drinking with body mass index (BMI) on hepatic steatosis. METHODS: Data
      from the population-based Study of Health in Pomerania (SHIP) conducted in north
      east Germany comprising 4009 adults were used. Alcohol consumption was assessed
      by self-report. Serum carbohydrate-deficient transferrin (CDT) was analysed as
      biomarker for alcohol consumption. Hepatic steatosis was diagnosed by
      ultrasonography. RESULTS: Analyses revealed a dose-response relationship between
      average daily alcohol consumption and hepatic steatosis in men starting with a
      consumption of 20 g of alcohol per day [adjusted odds ratio (OR) compared to
      abstainers 1.53; 95% confidence interval (CI) 1.15-2.05]. Using CDT as
      alternative exposure variable confirmed these results. Binge drinking was
      associated with hepatic steatosis in men (adjusted OR of binge drinkers compared
      to nonbinge drinkers 1.36, 95% CI 1.06-1.74). The likelihood of having hepatic
      steatosis increased in men and women with increasing levels of average daily
      alcohol consumption in combination with overweight or obesity. Similarly, binge
      drinking in combination with overweight or obesity enhanced the likelihood of
      having hepatic steatosis. CONCLUSIONS: Overweight or obesity substantially
      enhanced the effect of high levels of average daily alcohol consumption and binge
      drinking on hepatic steatosis in the present study population. This finding
      underlines the necessity to screen for multiple risk factors in the prevention of
      hepatic steatosis.

PMID- 25588770
TI  - Anterior chamber depth measurement using ultrasound to assess elevated
      intraocular pressure.

PMID- 25588771
TI  - Circulating microRNA predicts insensitivity to glucocorticoid therapy in Graves'
      ophthalmopathy.
AB  - Glucocorticoid (GC) insensitivity occurs commonly in Graves' ophthalmopathy (GO),
      and GC therapy is associated with major adverse effects. A reliable and easily
      accessible biomarker is required to predict the outcome of GC therapy. This study
      aimed to evaluate the performance of circulating microRNA (miRNA) to predict GC
      insensitivity in GO patients. A total of 35 consecutive patients were included in
      this study. A cumulative dose of 4.5 g of methylprednisolone (MP) was
      administered intravenously for 12 weeks. Pretreatment serum miRNAs from the best-
      (N = 5) and worst- (N = 4) responding patients were profiled using miScript PCR
      arrays and validated by quantitative PCR in all patients. We calculated the
      predictive value of pretreatment assays of serum miRNAs with regard to GC
      insensitivity. We further investigated the roles of target miRNAs in modulating
      NF-kappaB activity and restoring transrepression of an NF-kappaB reporter by
      dexamethasone. Nine miRNAs displayed significant differences between responsive
      and resistant patients by miScript PCR arrays. Validation of the top two miRNAs
      in all 35 patients confirmed a significantly lower serum level of miR-224-5p (p =
      0.0048) in resistant patients. A multivariate logistic regression model
      identified a composite biomarker combining baseline serum miR-224-5p and TRAb was
      independently associated with GC response (OR: 2.565, 95 % CI 1.011-6.505, p =
      0.047). Receiver operating characteristic (ROC) curves analysis revealed the
      composite marker combining miR-224-5p and TRAb led to a 91.67 % positive
      prediction value (PPV) and a 69.56 % negative prediction value (NPV) with regard
      to GC resistance. Overexpression of miR-224-5p restored transrepression of the NF
      kappaB reporter by dexamethasone under induced resistance, which may be via
      targeting GSK-3beta to increase GR protein level. Our study demonstrated baseline
      serum miR-224-5p was associated with GC sensitivity in GO and in vitro
      overexpression of miR-224-5p restored GC sensitivity in a resistant cell model. A
      parameter combined serum miR-224-5p and TRAb could effectively predict GC
      sensitivity in GO patients.

PMID- 25588773
TI  - Systematic evaluation of bundled SPC water for biomolecular simulations.
AB  - In bundled SPC water models, the relative motion of groups of four water
      molecules is restrained by distance-dependent potentials. Bundled SPC models have
      been used in hybrid all-atom/coarse-grained (AA/CG) multiscale simulations, since
      they enable to couple atomistic SPC water with supra-molecular CG water models
      that effectively represent more than a single water molecule. In the present
      work, we systematically validated and critically tested bundled SPC water models
      as solvent for biomolecular simulations. To that aim, we investigated both
      thermodynamic and structural properties of various biomolecular systems through
      molecular dynamics (MD) simulations. Potentials of mean force of dimerization of
      pairs of amino acid side chains as well as hydration free energies of single side
      chains obtained with bundled SPC and standard (unrestrained) SPC water agree
      closely with each other and with experimental data. Decomposition of the
      hydration free energies into enthalpic and entropic contributions reveals that in
      bundled SPC, this favorable agreement of the free energies is due to a larger
      degree of error compensation between hydration enthalpy and entropy. The
      Ramachandran maps of Ala3, Ala5, and Ala7 peptides are similar in bundled and
      unrestrained SPC, whereas for the (GS)2 peptide, bundled water leads to a slight
      overpopulation of extended conformations. Analysis of the end-to-end distance
      autocorrelation times of the Ala5 and (GS)2 peptides shows that sampling in more
      viscous bundled SPC water is about two times slower. Pronounced differences
      between the water models were found for the structure of a coiled-coil dimer,
      which is instable in bundled SPC but not in standard SPC. In addition, the
      hydration of the active site of the serine protease alpha-chymotrypsin depends on
      the water model. Bundled SPC leads to an increased hydration of the active site
      region, more hydrogen bonds between water and catalytic triad residues, and a
      significantly slower exchange of water molecules between the active site and the
      bulk. Our results form a basis for assessing the accuracy that can be expected
      from bundled SPC water models. At the same time, this study also highlights the
      importance of evaluating beforehand the effects of water bundling on the
      biomolecular system of interest for a particular multiscale simulation
      application. 

PMID- 25588772
TI  - The fat body mass increase after adjuvant androgen deprivation therapy is
      predictive of prostate cancer outcome.
AB  - Androgen deprivation therapy (ADT) leads to important changes in body
      composition. No data are currently available about the relationship between these
      treatment-related changes and patient outcome. Using dual-energy X-ray
      absorptiometry, bone mineral density (BMD), fat body mass (FBM), and lean body
      mass (LBM) were determined at baseline, and after 1 and 2 years in 53 non
      metastatic prostate cancer (PC) patients with high-risk disease treated with
      adjuvant ADT. Changes in these parameters were correlated with patient outcome in
      terms of adverse skeletal events, disease recurrence, and overall survival. ADT
      led to a significant decrease in BMD (p < 0.03) and LBM (p < 0.03), and an
      increase in FBM, (p < 0.0001). Changes in BMD failed to show any relationship
      with time to skeletal-related events (SRE), disease recurrence, and death. FBM
      increase was a significant predictor of higher risk of SRE [hazard ratio (HR)
      3.024, 95 % CI 1.004-10.353, p < 0.02], higher risk of death (HR 2.373, 95 % CI
      1.012-5.567, p = 0.04), and a non-significant higher risk of disease recurrence
      (HR 2.219, 95 % CI 0.956-5.150, p = 0.13). LBM decrease did not correlate with
      either time to SRE or survival, while a non-significant association with disease
      recurrence (HR 1.550, 95 % CI 0.670-3.605, p = 0.06) was observed. The early
      increase in FBM may provide predictive information of poor outcome in PC patients
      given ADT. These data suggest that the adoption of early preventive measures
      aiming to reduce fat increase can potentially reduce the morbidity and mortality
      risk.

PMID- 25588774
TI  - Homolytic H2 cleavage by a mercury-bridged Ni(I) pincer complex [{(PNP)Ni}2{MU
      Hg}].
AB  - Reduction of the pincer nickel(ii) complex [(PNP)NiBr] with sodium amalgam
      (Na/Hg) forms the mercury-bridged dimer [{(PNP)Ni}2{MU-Hg}], which homolytically
      cleaves dihydrogen to form [(PNP)NiH]. Reversible CO2 insertion into the Ni-H
      bond is observed for [(PNP)NiH], forming the monodentate kappa(1)O-formate
      complex [(PNP)NiOC(O)H]. 

PMID- 25588775
TI  - Perioperative catabolism.
AB  - PURPOSE: This article reviews the pathophysiology, clinical relevance, and
      therapy of the catabolic response to surgical stress. PRINCIPLE FINDINGS: The key
      clinical features of perioperative catabolism are hyperglycemia and loss of body
      protein, both metabolic consequences of impaired insulin function. Muscle
      weakness and (even moderate) increases in perioperative blood glucose are
      associated with morbidity after major surgery. Although the optimal glucose
      concentration for improving clinical outcomes is unknown, most medical
      associations recommend treatment of random blood glucose > 10 mmol.L(-1).
      Neuraxial anesthesia blunts the neuroendocrine stress response and enhances the
      anabolic effects of nutrition. There is evidence to suggest that the avoidance of
      preoperative fasting prevents insulin resistance and accelerates recovery after
      major abdominal surgery. CONCLUSIONS: Current anticatabolic therapeutic
      strategies include glycemic control and perioperative nutrition in combination
      with optimal pain control and the avoidance of preoperative starvation. All these
      elements are part of Enhanced Recovery After Surgery (ERAS) programs.

PMID- 25588778
TI  - Spectroscopic and theoretical studies of acid-base behaviors of N-confused
      porphyrins: effects of meso-aryl substituents.
AB  - The acid-base properties of a series of meso-aryl-substituted N-confused
      porphyrins (NCPs) were examined in aqueous sodium dodecyl sulfate (SDS) micellar
      solutions by both spectrophotometric methods and theoretical calculations.
      Reflecting the unsymmetrical structure of NCP having an outward-pointing pyrrolic
      nitrogen atom, the first and second protonations were distinguishable in the
      absorption and (1)H NMR spectra, unlike for porphyrins, and the pK3 and pK4
      values were determined discretely. The individual basicities of the NCPs were
      directly related to the inductive effect of para substituents on the meso-phenyl
      groups: A linear relationship between the pK3 (pK4) and Hammett sigmapara
      parameters was revealed. In the case of deprotonation, the structure of
      monoanionic NCP species was similarly characterized by the absorption and (1)H
      NMR spectra. For the second deprotonation, the pK1 value was determined to be
      11.39 for the NCP derivative with pentafluorophenyl groups. DFT calculations
      support the changes in electronic structures and aromaticity of the cationic and
      anionic species. It is demonstrated that NCPs are easily protonated and
      deprotonated compared to the corresponding regular congeners. 

PMID- 25588776
TI  - Serum-free isolation and culture system to enhance the proliferation and bone
      regeneration of adipose tissue-derived mesenchymal stem cells.
AB  - Cell therapy using human mesenchymal stem cells (MSCs) is an attractive approach
      for many refractory diseases. Adipose tissue-derived mesenchymal stem cells (AT
      MSCs) are considered as a favorable tool due to its abundance in the body, easy
      proliferation, and high cytokine production potency. In order to avoid the risks
      associated with the use of fetal bovine serum (FBS) in culture that includes
      batch variations and contamination with pathogens, development of serum-free
      culture system has been initiated. We have formulated a completely serum-free
      culture medium (SFM) that could be used not only for the expansion of AT-MSCs but
      also for initial isolation. We demonstrate that the AT-MSCs isolated and cultured
      in serum-free medium (AT-MSCs/SFM) possess high proliferation capacity and
      differentiation potency to osteoblast, adipocyte, and chondrocyte lineages in
      vitro. In in vivo bone fraction model analysis, AT-MSCs/SFM showed higher bone
      repair potency and quality of the regenerated bone than the cells cultured in
      serum-containing medium (AT-MSCs/SCM). This was attributed to the (i) presence of
      translated cells in the bone, as evidenced by in vivo imaging of the illuminated
      translated cells and (ii) high level of expression and induction capacity of AT
      MSCs/SFM for cytokine BMP2, CCL2, and CCL5. Taken together, we report a new serum
      free culture system for AT-MSCs that is suitable for cell therapy. 

PMID- 25588777
TI  - Development of a sensitive in vitro assay to quantify the biological activity of
      pro-inflammatory phorbol esters in Jatropha oil.
AB  - New health safety concerns may arise from the increasing production and use of
      Jatropha oil, a biodiesel feedstock that also contains toxic, pro-inflammatory,
      and co-carcinogenic phorbol esters. Based on the exceptional sensitivity of Madin
      Darby canine kidney (MDCK) cells to the model phorbol ester 12-O
      tetradecanoylphorbol-13-acetate (TPA), a robust bioassay was developed to
      quantify the biological activity of Jatropha phorbol esters directly in oil,
      without sample extraction. We first verified that the characteristic response of
      MDCK cells to TPA was also observed following direct exposure to phorbol esters
      in Jatropha oil. We further confirmed that similarly to TPA, Jatropha oil's
      phorbol esters can activate protein kinase C (PKC). We then assessed the
      transcriptional response of MDCK cells to Jatropha oil exposure by measuring the
      expression of cyclooxygenase-2 (COX-2), a gene involved in inflammatory processes
      which is strongly upregulated following PKC activation. Based on the
      parameterization of a TPA dose-response curve, the transcriptional response of
      MDCK cells to Jatropha oil exposure was expressed in term of TPA toxic equivalent
      (TEQ), a convenient metric to report the inflammatory potential of complex
      mixtures. The sensitive bioassay described in this manuscript may prove useful
      for risk assessment, as it provides a quantitative method and a convenient metric
      to report the inflammatory potential of phorbol esters in Jatropha oil. This
      bioassay may also be adapted for the detection of bioactive phorbol esters in
      other matrices. 

PMID- 25588779
TI  - Lipidomic profiling of sinus mucosa from patients with chronic rhinosinusitis.
AB  - Sinusitis is a cause of significant morbidity, substantial healthcare costs, and
      negative effects on quality of life. The primary objective of this study is to
      characterize the previously unknown lipid profile of sinonasal mucosa from
      patients with chronic rhinosinusitis (CRS) and from controls. Sinus mucosa
      samples were analyzed from 9 CRS patients with concomitant nasal polyps, 11 CRS
      patients without polyps, and 12 controls. Ten lone polyp samples were also
      analyzed. Samples were subjected to a modified Bligh/Dyer lipid extraction, then
      high performance thin layer chromatography (HPTLC), combined gas
      chromatography/electron impact-mass spectrometry (GC/EI-MS), and flow
      injection/electrospray ionization-tandem mass spectrometry (FI/ESI-MS/MS). Data
      was analyzed for identification and profiling of major components. HPTLC revealed
      an array of species reflecting the lipid complexity of the samples. GC/EI-MS
      revealed cholesterol and several fatty acids. FI/ESI-MSMS revealed numerous lipid
      species, namely a host of phosphatidylcholines, phosphatidylethanolamines,
      ceramides and cholesteryl esters, but no detectable amounts of
      phosphatidyinositols or sulfated lipids. These results are a first step to
      uncover unique molecular biomarkers in CRS. 

PMID- 25588780
TI  - Patterns of relapse in extrapulmonary small cell carcinoma: retrospective
      analysis of outcomes from two cancer centres.
AB  - OBJECTIVES: We conducted a retrospective review of patients with extrapulmonary
      small cell carcinomas (EPSCCs) to explore the distribution, treatments, patterns
      of relapse and outcomes by primary site. SETTING: We have reviewed the outcomes
      of one of the largest data sets of consecutive patients with EPSCC identified
      from two major cancer centres. PARTICIPANTS: Consecutive patients with a
      histopathological diagnosis of EPSCC from the two institutions were
      retrospectively identified. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes were
      evaluated including stage at presentation, treatments given, sites of relapse,
      time to distant relapse, progression-free survival and overall survival (OS).
      RESULTS: From a total 159 patients, 114 received first-line chemotherapy, 80.5%
      being platinum-based. Response rate was 48%. Commonest primary sites were
      genitourinary and gynaecological. 44% of patients presented with metastatic
      disease. 55.9% relapsed with liver the commonest site, whereas only 2.5%
      developed brain metastases. Median OS was 13.4 months for all patients, 7.6
      months and 19.5 months for those with metastatic and non-metastatic disease,
      respectively. Gynaecological and head and neck patients had significantly better
      OS compared to gastrointestinal patients. CONCLUSIONS: EPSCCs demonstrate high
      response rates to chemotherapy and high rates of distant metastases. Primary
      sites may influence prognosis, and survival is optimal with a radical strategy.
      Brain metastases are rare and we therefore do not recommend prophylactic cranial
      irradiation.

PMID- 25588781
TI  - Epidemiology of psoriasis and palmoplantar pustulosis: a nationwide study using
      the Japanese national claims database.
AB  - OBJECTIVE: The primary objective was to estimate the national prevalence of
      psoriasis and palmoplantar pustulosis (PPP) in Japan. Secondary objectives were
      to determine (1) whether psoriasis and PPP disease activity varies by season, and
      (2) whether disease severity is associated with concurrent diabetes mellitus,
      hyperlipidaemia and hypertension. SETTINGS: Patients with a psoriasis or PPP
      diagnosis code between April 2010 and March 2011 were identified using a Japanese
      national database. PARTICIPANTS: 565 903 patients with psoriasis or PPP were
      identified. No patient was excluded. PRIMARY AND SECONDARY OUTCOME MEASURES:
      National prevalence was calculated using census data. We estimated the difference
      in the proportion of patients who used healthcare services, as a proxy for
      disease activity, between the hot and cold seasons and the difference in the
      standardised prevalence of comorbidities between severe and mild disease. The
      measures were estimated separately for the two broad disease categories of
      psoriasis and PPP but not in all patients as planned because the two disease
      categories had major differences. RESULTS: The national prevalence of psoriasis
      and PPP was 0.34% (95% CI 0.34% to 0.34%) and 0.12% (0.12% to 0.12%),
      respectively. The difference in the proportion of patients who used healthcare
      services in the hot compared to the cold season was -0.3% (-0.5% to -0.1%) for
      psoriasis and 10.0% (9.8% to 10.3%) for PPP. The difference in the standardised
      prevalence between severe and mild psoriasis was 3.1% (2.7% to 3.4%), 3.2% (2.8%
      to 3.6%) and 5.1% (4.7% to 5.6%) for concurrent diabetes mellitus,
      hyperlipidaemia and hypertension, respectively. No significant difference in the
      prevalence of comorbidity was observed for PPP. CONCLUSIONS: The national
      prevalence, seasonal variation in disease activity and prevalence of
      comorbidities in Japanese patients with psoriasis and PPP estimated in this
      descriptive study may be used as basic information for future studies.

PMID- 25588782
TI  - Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double
      blind, randomised, placebo-controlled study.
AB  - OBJECTIVE: To estimate the efficacy of a probiotic yogurt compared to a
      pasteurised yogurt for the prevention of antibiotic-associated diarrhoea in
      children. DESIGN AND SETTING: This was a multisite, randomised, double-blind,
      placebo-controlled clinical trial conducted between September 2009 and 2012. The
      study was conducted through general practices and pharmacies in Launceston,
      Tasmania, Australia. PARTICIPANTS AND INTERVENTIONS: Children (aged 1-12 years)
      prescribed antibiotics, were randomised to receive 200 g/day of either yogurt
      (probiotic) containing Lactobacillus rhamnosus GG (LGG), Bifidobacterium lactis
      (Bb-12) and Lactobacillus acidophilus (La-5) or a pasteurised yogurt (placebo)
      for the same duration as their antibiotic treatment. OUTCOMES: Stool frequency
      and consistency were recorded for the duration of treatment plus 1 week. Primary
      outcome was stool frequency and consistency, classified at different levels of
      diarrhoea severity. Due to the small number of cases of diarrhoea, comparisons
      between groups were made using Fisher's exact analysis. RESULTS: 72 children
      commenced and 70 children (36 placebo and 34 probiotic) completed the trial.
      There were no incidents of severe diarrhoea (stool consistency >=6, >=3
      stools/day for >=2 consecutive days) in the probiotic group and six in the
      placebo group (Fisher's exact p=0.025). There was also only one episode of minor
      diarrhoea (stool consistency >=5, >=2 stools/day for >=2 days in the probiotic
      group compared to 21 in the placebo group (Fisher's exact p<0.001). The probiotic
      group reported fewer adverse events (1 had abdominal pain, 1 vomited and 1 had
      headache) than the placebo group (6 had abdominal pain, 4 had loss of appetite
      and 1 had nausea). CONCLUSIONS: A yogurt combination of LGG, La-5 and Bb-12 is an
      effective method for reducing the incidence of antibiotic-associated diarrhoea in
      children. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials
      Registry ACTRN12609000281291.

PMID- 25588783
TI  - The African, Caribbean and European (ACE) Pathways to Care study: a qualitative
      exploration of similarities and differences between African-origin, Caribbean
      origin and European-origin groups in pathways to care for psychosis.
AB  - OBJECTIVES: This paper reports on a qualitative exploration of the reasons for
      differences in pathways to care and duration of untreated psychosis (DUP) in the
      African, Caribbean and European (ACE) Pathways to Care study from the perspective
      of respondents to the study and their families. SETTING: Ontario, Canada.
      PARTICIPANTS: Thirty-four participants in total. Twenty-five young people who had
      experienced a first episode of psychosis and nine family members. Participants
      were part of the ACE Pathways to Care study. DESIGN: We implemented six focus
      groups. Furthermore, we implemented four in-depth interviews with two African
      origin young women, one Caribbean-origin woman, and one European-origin woman
      with lived experience of psychosis. RESULTS: Factors that influenced help-seeking
      delays across the three groups were: personal awareness of symptoms, family
      members' knowledge of psychotic symptoms and knowledge of mental health services.
      Youth and their family members described how stigma played a key role in pathways
      to care by stopping them from asking for help. The way in which stigma operated
      on the three groups' members, from feeling ashamed to feeling guilty for their
      mental illnesses, helped to explain differences in DUP between the groups. Guilt
      feelings emerged as a prominent theme among members from the African and
      Caribbean groups and it was not discussed in the European focus group. Delay in
      entering into first-episode psychosis programmes was also influenced by the
      stigma perceived by young people in healthcare settings. This had an impact on
      the therapeutic relationships, disclosure of symptoms and overall trust in the
      healthcare system. CONCLUSIONS: The findings of this paper suggest that stigma,
      especially internalised stigma, may operate in different ways in European-origin,
      African-origin and Caribbean-origin groups. These findings could inform the
      development of more equitable services for people in early stages of psychosis.

PMID- 25588784
TI  - Low-dose dexamethasone as a treatment for women with heavy menstrual bleeding:
      protocol for response-adaptive randomised placebo-controlled dose-finding
      parallel group trial (DexFEM).
AB  - INTRODUCTION: Heavy menstrual bleeding (HMB) diminishes individual quality-of
      life and poses substantial societal burden. In HMB endometrium, inactivation of
      cortisol (by enzyme 11beta hydroxysteroid dehydrogenase type 2 (11betaHSD2)), may
      cause local endometrial glucocorticoid deficiency and hence increased
      angiogenesis and impaired vasoconstriction. We propose that 'rescue' of luteal
      phase endometrial glucocorticoid deficiency could reduce menstrual bleeding.
      METHODS AND ANALYSIS: DexFEM is a double-blind response-adaptive parallel-group
      placebo-controlled trial in women with HMB (108 to be randomised), with active
      treatment the potent oral synthetic glucocorticoid dexamethasone, which is
      relatively resistant to 11betaHSD2 inactivation. Participants will be aged over
      18 years, with mean measured menstrual blood loss (MBL) for two screening cycles
      >=50 mL. The primary outcome is reduction in MBL from screening. Secondary end
      points are questionnaire assessments of treatment effect and acceptability.
      Treatment will be for 5 days in the mid-luteal phases of three treatment
      menstrual cycles. Six doses of low-dose dexamethasone (ranging from 0.2 to 0.9 mg
      twice daily) will be compared with placebo, to ascertain optimal dose, and
      whether this has advantage over placebo. Statistical efficiency is maximised by
      allowing randomisation probabilities to 'adapt' at five points during enrolment
      phase, based on the response data available so far, to favour doses expected to
      provide greatest additional information on the dose-response. Bayesian Normal
      Dynamic Linear Modelling, with baseline MBL included as covariate, will determine
      optimal dose (re reduction in MBL). Secondary end points will be analysed using
      generalised dynamic linear models. For each dose for all end points, a 95%
      credible interval will be calculated for effect versus placebo. ETHICS AND
      DISSEMINATION: Dexamethasone is widely used and hence well-characterised safety
      wise. Ethical approval has been obtained from Scotland A Research Ethics
      Committee (12/SS/0147). Trial findings will be disseminated via open-access peer
      reviewed publications, conferences, clinical networks, public lectures, and our
      websites. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01769820; EudractCT
      2012-003405-98.

PMID- 25588786
TI  - Elevated matrix metalloproteinase-7 expression promotes metastasis in human lung
      carcinoma.
AB  - BACKGROUND: Matrix metalloproteinase 7 (MMP-7) promotes tumor invasion and
      metastasis in several cancers. However, its role in lung cancer progression is
      understudied. In this study, we investigated the correlation between MMP-7
      expression and lung cancer pathology. METHODS: We searched the databases PubMed,
      Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, China BioMedicine (CBM)
      and China National Knowledge Infrastructure (CNKI) for scientific literature
      relevant to MMP-7 and lung cancer. Carefully selected studies were pooled and ORs
      with 95% CI were calculated. Subgroup analyses and publication bias were analyzed
      to understand the retrieved data in greater detail. Version 12.0 STATA software
      was used for statistical analysis. RESULTS: We retrieved a total of 121 studies
      through database searches. Finally, 14 cohort studies satisfied our
      inclusion/exclusion criteria, and these 14 studies, published between 2004 and
      2012, were selected for meta-analysis to understand the influence of MMP-7
      expression in lung cancer progression. Our results showed consistent differences
      in MMP-7 expression when comparisons were made between TNM I-II versus III-IV (OR
      = 1.82, 95% CI: 1.19 to 2.78, P = 0.006); histologic grade 1 to 2 versus 3 to 4
      (OR = 1.67, 95% CI: 1.14 to 2.42, P = 0.008); and lymph node-negative versus
      lymph node-positive samples (OR = 2.81, 95% CI: 1.73 to 4.58, P <0.001), with
      significantly higher MMP-7 expression levels found in the more advanced stages.
      Subgroup analysis showed that age was not the factor influencing the associations
      between histologic grade, LN metastasis and MMP-7 expression in lung cancer
      patients, as both under 60 and over 60 age groups showed strong correlations (all
      P <0.05). However, when TNM staging was analyzed for its association with MMP-7
      expression, only patients under age 60 showed a statistically significant
      correlation. CONCLUSIONS: Our meta-analysis results revealed that MMP-7
      overexpression is associated with advanced TNM and histological grades, and is
      linked to aggressive LN metastasis in lung cancer patients; thus MMP-7 is a
      useful biomarker to assess the disease status in lung cancers.

PMID- 25588785
TI  - Efficacy of metformin in pregnant obese women: a randomised controlled trial.
AB  - INTRODUCTION: Increasing evidence suggests obesity has its origins prior to
      birth. There is clear correlation between maternal obesity, high birthweight and
      offspring risk of obesity in later life. It is also clear that women who are
      obese during pregnancy are at greater risk of adverse outcomes, including
      gestational diabetes and stillbirth. The mechanism(s) by which obesity causes
      these problems is unknown, although hyperglycaemia and insulin resistance are
      strongly implicated. We present a protocol for a study to test the hypothesis
      that metformin will improve insulin sensitivity in obese pregnant women, thereby
      reducing the incidence of high birthweight babies and other pregnancy
      complications. METHODS AND ANALYSIS: The Efficacy of Metformin in Pregnant Obese
      Women, a Randomised controlled (EMPOWaR) trial is a double-masked randomised
      placebo-controlled trial to determine whether metformin given to obese (body mass
      index >30 kg/m(2)) pregnant women from 16 weeks' gestation until delivery reduces
      the incidence of high birthweight babies. A secondary aim is to test the
      mechanism(s) of any effect. Obese women with a singleton pregnancy and normal
      glucose tolerance will be recruited prior to 16 weeks' gestation and prescribed
      study medication, metformin or placebo, to be taken until delivery. Further study
      visits will occur at 28 and 36 weeks' gestation for glucose tolerance testing and
      to record anthropometric measurements. Birth weight and other measurements will
      be recorded at time of delivery. Anthropometry of mother and baby will be
      performed at 3 months postdelivery. As of January 2014, 449 women had been
      randomised across the UK. ETHICS AND DISSEMINATION: The study will be conducted
      in accordance with the principles of Good Clinical Practice. A favourable ethical
      opinion was obtained from Scotland A Research Ethics Committee, reference number
      10/MRE00/12. Results will be disseminated at conferences and published in peer
      reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN51279843.

PMID- 25588787
TI  - Chromatin looping and eRNA transcription precede the transcriptional activation
      of gene in the beta-globin locus.
AB  - Enhancers are closely positioned with actively transcribed target genes by
      chromatin looping. Non-coding RNAs are often transcribed on active enhancers,
      referred to as eRNAs (enhancer RNAs). To explore the kinetics of enhancer
      promoter looping and eRNA transcription during transcriptional activation, we
      induced the beta-globin locus by chemical treatment and analysed cross-linking
      frequency between the beta-globin gene and locus control region (LCR) and the
      amount of eRNAs transcribed on the LCR in a time course manner. The cross-linking
      frequency was increased after chemical induction but before the transcriptional
      activation of gene in the beta-globin locus. Transcription of eRNAs was increased
      in concomitant with the increase in cross-linking frequency. These results show
      that chromatin looping and eRNA transcription precedes the transcriptional
      activation of gene. Concomitant occurrence of the two events suggests functional
      relationship between them.

PMID- 25588788
TI  - Association between neighborhood walkability and GPS-measured walking, bicycling
      and vehicle time in adolescents.
AB  - OBJECTIVES: To investigate relations of walking, bicycling and vehicle time to
      neighborhood walkability and total physical activity in youth. METHODS:
      Participants (N=690) were from 380 census block groups of high/low walkability
      and income in two US regions. Home neighborhood residential density, intersection
      density, retail density, entertainment density and walkability were derived using
      GIS. Minutes/day of walking, bicycling and vehicle time were derived from
      processing algorithms applied to GPS. Accelerometers estimated total daily
      moderate-to-vigorous physical activity (MVPA). Models were adjusted for nesting
      of days (N=2987) within participants within block groups. RESULTS: Walking
      occurred on 33%, active travel on 43%, and vehicle time on 91% of the days
      observed. Intersection density and neighborhood walkability were positively
      related to walking and bicycling and negatively related to vehicle time.
      Residential density was positively related to walking. CONCLUSIONS: Increasing
      walking in youth could be effective in increasing total physical activity. Built
      environment findings suggest potential for increasing walking in youth through
      improving neighborhood walkability.

PMID- 25588790
TI  - Immunogenic peptide discovery in cancer genomes.
AB  - As immunotherapies to treat malignancy continue to diversify along with the tumor
      types amenable to treatment, it will become very important to predict which
      treatment is most likely to benefit a given patient. Tumor neoantigens, novel
      peptides resulting from somatic tumor mutations and recognized by the immune
      system as foreign, are likely to contribute significantly to the efficacy of
      immunotherapy. Multiple in silico methods have been developed to predict whether
      peptides, including tumor neoantigens, will be presented by the major
      histocompatibility complex (MHC) Class I or Class II, and interact with the T
      cell receptor (TCR). The methods for neoantigen prediction will be reviewed here,
      along with the most important examples of their use in the field of oncology.

PMID- 25588791
TI  - Non-operative advances: what has happened in the last 50 years in paediatric
      surgery?
AB  - Paediatric surgeons remain paediatric clinicians who have the unique skill set to
      treat children with surgical problems that may require operative intervention.
      Many of the advances in paediatric surgical care have occurred outside the
      operating theatre and have involved significant input from medical, nursing and
      allied health colleagues. The establishment of neonatal intensive care units,
      especially those focusing on the care of surgical infants, has greatly enhanced
      the survival rates and long-term outcomes of those infants with major congenital
      anomalies requiring surgical repair. Educational initiatives such as the advanced
      trauma life support and emergency management of severe burns courses have
      facilitated improved understanding and clinical care. Paediatric surgeons have
      led with the non-operative management of solid organ injury following blunt
      abdominal trauma. Nano-crystalline burn wound dressings have enabled a reduced
      frequency of painful dressing changes in addition to effective antimicrobial
      efficacy and enhanced burn wound healing. Burns care has evolved so that many
      children may now be treated almost exclusively in an ambulatory care setting or
      as day case-only patients, with novel technologies allowing accurate prediction
      of burn would outcome and planning of elective operative intervention to achieve
      burn wound closure. 

PMID- 25588789
TI  - The long-term dynamics of Campylobacter colonizing a free-range broiler breeder
      flock: an observational study.
AB  - A free-range broiler breeder flock was studied in order to determine the natural
      patterns of Campylobacter colonization over a period of 63 weeks. Campylobacter
      sequence types (STs) were not mutually exclusive and on average colonized only
      17.7% of the birds tested at any time. Campylobacter STs typically reached a peak
      in prevalence upon initial detection in the flock before tailing off, although
      the ST and antigenic flaA short variable region in combination were stable over a
      number of months. There was evidence that, with a couple of exceptions, the
      ecology of C. jejuni and C. coli differed, with the latter forming a more stable
      population. Despite being free range, no newly colonizing STs were detected over
      a 6-week period in autumn and a 10-week period in winter, towards the end of the
      study. There was limited evidence that those STs identified among broiler chicken
      flocks on the same farm site were likely to colonize the breeder flock earlier
      (R(2) 0.16, P 0.01). These results suggest that there is natural control of
      Campylobacter dynamics within a flock which could potentially be exploited in
      designing new intervention strategies, and that the two different species should
      perhaps be considered separately. 

PMID- 25588792
TI  - Quantitative motor unit action potential analysis of supraspinatus,
      infraspinatus, deltoideus and biceps femoris muscles in adult Royal Dutch sport
      horses.
AB  - REASONS FOR PERFORMING STUDY: Reference values for quantitative electromyography
      (QEMG) in shoulder and hindlimb muscles of horses are limited. OBJECTIVES: To
      determine normative data on QEMG analysis of supraspinatus (SS), infraspinatus
      (IS), deltoideus (DT) and biceps femoris (BF) muscles. STUDY DESIGN: Experimental
      observational study and retrospective case series. METHODS: Seven adult healthy
      Royal Dutch sport horses underwent quantitative motor unit action potential
      analysis of each muscle using commercial electromyography equipment. Measurements
      were made according to published methods. One-way ANOVA was used to compare
      quantitative motor unit action potential variables between muscles, with post hoc
      testing according to Bonferroni, with significance set at P<0.05. The QEMG and
      clinical information from horses with lower motor neuron disorders (n = 7) or
      myopathy (n = 4) were summarised retrospectively. RESULTS: The 95% confidence
      intervals of duration, amplitude, phases, turns, area and size index of
      quantitative motor unit action potential were 8.7-10.4 ms, 651-867 MUV, 3.2-3.7,
      3.7-4.7, 1054-1457 MUV.ms and 1.1-1.5 for SS, 9.6-11.0 ms, 779-1082 MUV, 3.3-3.7,
      3.8-4.7, 1349-2204 MUV.ms and 1.4-1.9 for IS, 6.0-9.1 ms, 370-691 MUV, 2.9-3.7,
      2.8-4.5, 380-1374 MUV.ms and 0.3-1.3 for DT and 5.7-7.8 ms, 265-385 MUV, 2.7-3.2,
      2.6-3.1, 296-484 MUV.ms and 0.2-0.5 for BF, respectively. Mean duration,
      amplitude, number of phases and turns, area and size index were significantly
      (P<0.01) higher in SS and IS than in DT and BF muscles. In addition, 4 of 7
      normal horses had >15% polyphasic motor unit action potentials in SS and IS
      muscles. CONCLUSIONS: Differences between muscles should be taken into account
      when performing QEMG in order to be able to distinguish normal horses from horses
      with suspected neurogenic or myogenic disorders. These normal data provide the
      basis for objective QEMG assessment of shoulder and hindlimb muscles.
      Quantitative electromyography appears to be helpful in diagnosing neuropathies
      and discriminating these from myopathies.

PMID- 25588794
TI  - Stress exposure and the risk for the onset of alcohol use disorders and nicotine
      dependence in deployed military personnel: the role of prior internalizing
      disorders.
AB  - OBJECTIVE: This prospective study aimed to investigate whether prior
      internalizing disorders (PIDs) moderate the relationship between stress exposure
      (SE) and the onset of alcohol use disorders (AUDs) and nicotine dependence (ND)
      in deployed military personnel. METHODS: 358 male soldiers were examined directly
      before and 12months after return from deployment using standardized interviews.
      Combat experiences, concerns about family disruptions, and difficult living and
      working environment were assessed as different aspects of SE. PID diagnoses (mood
      disorders (PMDs), anxiety disorders (PADs)) and substance use disorders were
      defined according to the DSM-IV-TR. RESULTS: PMDs were related to a stronger
      association between concerns about family disruptions and the risk of AUD onset
      (OR=7.7, 95% CI 1.8-32.8, p=0.006). The number of PID diagnoses (OR per
      diagnosis: 1.7, 95% CI 1.0-2.8, p=0.036) and PADs (OR: 2.6, 95% CI 1.1-6.3,
      p=0.038) were further related to a stronger association between difficult living
      and working environment and the risk of AUD onset. With regard to ND, PMDs were
      related to a weaker association between difficult living and working environment
      and the risk of ND onset (OR=0.4, 95% CI 0.2-0.8, p=0.013). CONCLUSIONS: PIDs
      might be related to an increased risk for the onset of AUDs but not ND following
      SE. This effect is probably restricted to specific constellations of PADs, PMDs,
      comorbid PIDs and specific aspects of SE. These critical constellations of PIDs
      and SE might be a promising target for future research and could contribute to
      the development of preventive measures to reduce the risk of AUDs following SE.

PMID- 25588793
TI  - Associations between childhood trauma and non-fatal overdose among people who
      inject drugs.
AB  - INTRODUCTION: Although people who inject drugs (IDU) remain at a high risk of
      accidental overdose, interventions that address overdose remain limited.
      Accordingly there is a continuing need to identify psychological and social
      factors that shape overdose risk. Despite being reported frequently among IDU,
      childhood trauma has received little attention as a potential risk factor for
      overdose. This study aims to evaluate relationships between non-fatal overdose
      and five forms of childhood maltreatment among a cohort of IDU in Vancouver,
      Canada. METHODS: Data was obtained from two prospective cohorts of IDU between
      December 2005 and May 2013. Multivariate generalized estimating equations (GEEs)
      were used to explore relationships between five forms of childhood trauma and non
      fatal overdose, adjusting for potential confounders. RESULTS: During the study
      period, 1697 IDU, including 552 (32.5%) women, were followed up. At baseline,
      1136 (67.0%) participants reported at least one form of childhood trauma, while 4
      9% reported a non-fatal overdose at each semi-annual follow-up. In multivariate
      analyses, physical [adjusted odds ratio (AOR): 1.36, 95% confidence interval
      (CI): 1.08-1.71], sexual (AOR: 1.48, CI: 1.17-1.87), and emotional abuse (AOR:
      1.54, CI: 1.22-1.93) and physical neglect (AOR: 1.28, CI: 1.01-1.62) were
      independently associated with non-fatal overdose (all p<0.05). CONCLUSIONS:
      Childhood trauma was common among participants, and reporting an experience of
      trauma was positively associated with non-fatal overdose. These findings
      highlight the need to provide intensive overdose prevention to trauma survivors
      and to incorporate screening for childhood trauma into health and social programs
      tailored to IDU.

PMID- 25588795
TI  - Arterial-left ventricular-left atrial coupling late after repair of aortic
      coarctation and interruption.
AB  - AIMS: This study aimed to explore the arterial-left ventricular (LV)-left atrial
      (LA) interaction in adolescents and young adults late after intervention for
      coarctation of the aorta (CoA) and interrupted aortic arch (IAA). METHODS AND
      RESULTS: Thirty-one (16 males) patients aged 23.4 +/- 6.3, at 20.6 +/- 5.2 years
      after intervention, and 31 controls were studied. Carotid arterial stiffness and
      intima-media thickness (IMT) and brachial-ankle pulse wave velocity were
      determined by radiofrequency-based echocardiography and oscillometry,
      respectively. Tissue Doppler and speckle tracking echocardiography (STE) were
      performed to assess, respectively, LV myocardial tissue velocities and linear and
      torsional deformation. Left atrial positive, negative, and total strain and
      strain rate at ventricular systole (aSRs), early diastole (aSRed), and atrial
      contraction (aSRac) were also determined using STE. Patients had significantly
      greater arterial stiffness and IMT than controls (all P < 0.05). Mitral annular
      systolic and diastolic velocities, LV longitudinal and radial strain and early
      diastolic strain rates, peak torsion and untwisting velocity, and LA peak
      positive and total strain, aSRs, aSRed, and aSRac were significantly lower in
      patients than in controls (all P < 0.05). Arterial stiffness correlated inversely
      with LV longitudinal strain and systolic and early diastolic strain rate (all P <
      0.05), while LA total strain and aSRed were associated positively with LV
      diastolic annular velocity, longitudinal SRe, and peak untwisting velocity (all P
      < 0.05). Multiple linear regression further revealed arterial stiffness as an
      independent determinant of LA total strain (beta = -1.3, P = 0.034). CONCLUSION:
      Our findings suggest impairment of arterial function and LV and LA mechanics in
      patients after CoA and IAA repair and implicate an abnormal arterial-LV-LA
      interaction.

PMID- 25588796
TI  - Utility of cardiac FDG-PET imaging coupled to magnetic resonance for the
      management of an acute myocarditis with non-informative endomyocardial biopsy.

PMID- 25588797
TI  - Association between pulmonary vein orientation and atrial fibrillation-free
      survival in patients undergoing endoscopic laser balloon ablation.
AB  - AIMS: Obtaining optimal pulmonary vein (PV) occlusion with the endoscopic laser
      balloon ablation system (EAS) can be difficult, hypothetically influenced by PV
      geometry. The aim of this study was to determine the impact of PV orientation on
      atrial fibrillation (AF)-free survival after PV isolation (PVI) using the EAS.
      METHODS AND RESULTS: Forty-three patients undergoing a single EAS PVI were
      included. Left atrial electrocardiogram -triggered computed tomography was
      performed in all patients prior to PVI. Of all four PVs, the orientation at the
      insertion in the left atrium was measured in both the transverse and frontal
      plane and assigned to one of the four orientation groups: ventral-caudal, dorsal
      caudal, ventral-cranial, and dorsal-cranial. Mean age was 56 years; 86% had
      paroxysmal AF. Overall, AF-free survival after a median follow-up of 18.2 months
      was 51.2%. AF-free survival varied between 21 and 88% depending on left upper PV
      orientation (P = 0.045). Furthermore, AF-free survival varied between 21 and 86%
      depending on left lower PV orientation (P = 0.010) and AF-free survival varied
      between 29 and 88% depending on right lower PV orientation (P = 0.053). No
      association was found between right upper PV orientation and AF-free survival
      after EAS PVI (P = 0.794). In multivariate analysis, only left lower PV
      orientation was associated with AF-free survival [hazards ratio (HR) 10.4, P =
      0.019]. CONCLUSION: PV orientation is associated with AF-free survival after EAS
      PVI. PV orientation assessment may be useful for selecting the most suitable
      patients for EAS PVI.

PMID- 25588798
TI  - Video-assisted transmitral resection of primary cardiac lipoma originated from
      the left ventricular apex.

PMID- 25588799
TI  - Evaluation of ischaemia in patients with atrial fibrillation: impact of stress
      protocol on myocardial perfusion imaging accuracy.
AB  - BACKGROUND: To evaluate the accuracy of myocardial perfusion imaging (MPI) on a
      novel cadmium-zinc-thelluride camera in detecting significant coronary artery
      disease (CAD) in patients with atrial fibrillation (AF). METHODS AND RESULTS:
      Seventy-four subjects with AF submitted to stress-rest MPI and coronary
      angiography were consecutively enrolled. One hundred and forty-eight patients in
      sinus rhythm, matched for age, sex, and type of stress-test protocol and with
      known coronary anatomy served as controls. The summed difference score, as
      measure of reversible myocardial ischaemia, was calculated. A coronary stenosis
      >=70% was considered significant. The prevalence of significant CAD did not
      differ between AF patients and controls. At receiving operating characteristic
      analysis MPI showed relevant accuracy in unmasking the presence of significant
      CAD both in AF and in control patients (areas under the curve 0.71 vs. 0.80, P
      for difference: 0.212). However, after stratifying patients according to the
      stress protocol, a significant interaction between the presence of AF and MPI
      diagnostic power was evident. While in the case of a vasodilator stress-test MPI
      diagnostic accuracy remained high in both groups of patients (P for difference:
      0.664), in those submitted to an exercise stress-test the diagnostic power of MPI
      was significantly lower in the presence of AF (P for difference: 0.039), because
      of a lower specificity. Interestingly, at multivariate analysis, a lower exercise
      duration (P = 0.017) was the major predictor of reduced MPI specificity.
      CONCLUSION: The presence of AF impairs MPI accuracy on the detection significant
      CAD. This effect was only apparent in the case of an exercise stress-test, while
      disappeared in patients submitted to vasodilator stress.

PMID- 25588800
TI  - (Tissue PET) Vascular metabolic imaging and peripheral plasma biomarkers in the
      evolution of chronic aortic dissections.
AB  - AIMS: Despite adequate medical management, dissection of the descending aorta
      (type B) may develop complications, including aneurysmal progression and
      eventually rupture. Partial false lumen thrombosis has been identified as a
      marker of adverse evolution in chronic dissection. The aim of this study was to
      test the ability of complementary information, provided by (18)F
      fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography
      (PET/CT) and peripheral biomarkers, to add pathophysiological significance and a
      prognostic value to morphological data. METHODS AND RESULTS: We explored serial
      aortic (18)F-FDG uptake by PET/CT imaging and plasma biomarkers in a series of 23
      patients with type B dissection to predict complications from initial data and to
      investigate potential associations with aneurysmal expansion during follow-up.
      Complications occurred in 17 patients. Acute initial characteristics associated
      with complications were male gender (P = 0.021), arterial hypertension (P =
      0.040), aortic dissection diameter (P = 0.0086), partial thrombosis of the false
      channel (P = 0.0046), and enhanced focal (18)F-FDG uptake (P = 0.045). During
      follow-up (mean 16.7 +/- 8.0 months), aneurysmal expansion was associated with
      false lumen morphology (P< 0.0001), quantitative (18)F-FDG uptake, (P = 0.0029),
      elevated plasma concentrations of biomarkers of platelets (P-selectin, P =
      0.0009) and thrombin activation (TAT complexes, P = 0.0075), and fibrinolysis
      (PAP complexes, P < 0.0001; D-dimers, P = 0.0006). Plasma markers of coagulation
      and fibrinolysis were related to false channel morphology, suggesting that
      thrombus biological dynamics may drive progressive expansion of type B
      dissections. CONCLUSION: Enhanced FDG uptake may be considered as a complementary
      imaging marker associated with secondary complications in type B dissections.
      During follow-up, aneurysmal progression is related to PET/CT and biomarkers of
      thrombus renewal and lysis.

PMID- 25588801
TI  - Prognostic value of Doppler echocardiographic-derived coronary flow velocity
      reserve of left anterior descending artery in octogenarians with stress
      echocardiography negative for wall motion criteria.
AB  - AIMS: Doppler-derived coronary flow velocity reserve (CFVR) of left anterior
      descending (LAD) artery is an effective tool to predict overall mortality. The
      aim was to investigate the capability of CFVR to predict outcome in an unselected
      cohort of patients older than 80 years having stress echo negative by wall motion
      criteria. METHODS AND RESULTS: The study group refers to 369 patients aged > 80
      years (156 men; mean age 83 +/- 2 years) who had undergone dipyridamole stress
      echocardiography with CFVR assessment of LAD artery of known (n = 144) or
      suspected (n = 225) coronary artery disease. Stress echocardiography was negative
      for wall motion criteria in all cases. Mean CFVR was 2.07 +/- 0.53. During a
      median follow-up of 21 months, there were 62 major adverse cardiac events (MACEs;
      45 deaths and 17 non-fatal myocardial infarctions). With a receiver operating
      characteristic analysis, a CFVR of <= 1.93 was the best cut-off for predicting
      mortality and MACE. At individual patient analysis, 152 (41%) subjects had a CFVR
      of < 1.93. Annual mortality was 9.8% in patients with CFVR <1.93 and 3.7% in
      those with CFVR > 1.93 (P = 0.001); an annual MACE rate was 14.8% in the former
      and 4.5% in the latter (P < 0.0001). Of 15 clinical and echocardiographic
      parameters analysed, CFVR <= 1.93 [hazard ratio (HR) = 2.17, 95% CI 1.14-4.10]
      and resting wall motion abnormality (RWMA; HR = 2.60; 95% CI 1.35-5.00) were
      multivariable indicators of mortality. Moreover, CFVR <= 1.93 (HR = 2.69, 95% CI
      1.56-4.67), and RWMA (HR = 2.38; 95% CI 1.31-4.33) were also strong independent
      predictors of MACEs. At incremental analysis, CFR <= 1.93 added prognostic
      information over clinical evaluation and RWMA when both mortality and MACE were
      taken as clinical end points. CONCLUSIONS: A reduced CFVR of LAD artery is a
      strong and independent indicator of both mortality and MACE, adding prognostic
      information over clinical evaluation and RWMA. Conversely, a preserved CFVR
      predicts a favourable outcome particularly in subjects with no RWMA.

PMID- 25588802
TI  - Identification and quantification of macrophage presence in coronary
      atherosclerotic plaques by optical coherence tomography.
AB  - AIMS: Vulnerable plaques are characterized by a high macrophage content. We
      investigated the optical coherence tomography (OCT) capability of identifying
      coronary plaque macrophage presence using tissue property indexes. METHODS AND
      RESULTS: Fifteen epicardial coronary arteries were imaged by OCT and subsequently
      analysed by histology. Correlating OCT-histological sections were identified and
      regions of interest (ROIs) were selected on both atherosclerotic plaques and
      normal appearing vessel tracts. OCT-derived tissue property indexes named
      normalized standard deviation (NSD), signal attenuation, and granulometry index
      were applied on ROIs to identify inflamed ROIs defined as a macrophage percentage
      >10 by histology. Forty-three paired samples (OCT frame and histology section)
      were considered suitable as ROIs for analysis. Eleven out of 43 ROIs were
      considered inflamed and the remaining 32 ROIs were non-inflamed on the basis of
      histological count of macrophage percentage. All OCT-derived tissue property
      indexes were positively correlated with macrophage percentage (P = 0.0001 for
      all). Receiver operating characteristic curve analysis showed that NSD,
      granulometry index, and signal attenuation had a significant area under the curve
      (area = 0.906, 0.804, and 0.793, respectively). A two-step algorithm requiring to
      first apply NSD with a cut-off value of 0.0570 followed by granulometry index was
      able to identify an inflamed ROI with a sensitivity of 100% and a specificity of
      96.8%. CONCLUSION: OCT was able to identify and quantify macrophage presence in
      coronary artery specimens using tissue property indexes. NSD and granulometry
      index showed the highest accuracy in identifying a significant plaque
      inflammation, especially if used together in a two-step algorithm.

PMID- 25588803
TI  - Management of gallbladder dyskinesia: patient outcomes following positive
      99mtechnetium (Tc)-labelled hepatic iminodiacetic acid (HIDA) scintigraphy with
      cholecystokinin (CCK) provocation and laparoscopic cholecystectomy.
AB  - AIMS: To evaluate clinical outcomes in patients with typical biliary pain, normal
      ultrasonic findings, and a positive (99m)technetium (Tc)-labelled hepatic
      iminodiacetic acid analogue (HIDA) scintigraphy with cholecystokinin (CCK)
      provocation indicating gallbladder dyskinesia, as per Rome III criteria,
      undergoing laparoscopic cholecystectomy (LC). METHODS AND MATERIALS: Consecutive
      patients undergoing LC for gallbladder dyskinesia were identified
      retrospectively. They were followed up by telephone interview and review of the
      electronic case records to assess symptom resolution. RESULTS: One hundred
      consecutive patients (median age 44; 80% female) with abnormal gallbladder
      ejection fraction (GB-EF <35%) were followed up for a median of 12 months (range
      2-80 months). Following LC, 84% reported symptomatic improvement and 52% had no
      residual pain. Twelve percent had persisting preoperative-type pain of either
      unchanged or worsening severity. Neither pathological features of chronic
      cholecystitis (87% of 92 incidences when histology available) nor reproduction of
      pain on CCK injection were significantly predictive of symptom outcome or pain
      relief post-LC. CONCLUSION: In one of the largest outcome series of gallbladder
      dyskinesia patients in the UK with a positive provocation HIDA scintigraphy
      examination and LC, the present study shows that the test is a useful functional
      diagnostic tool in the management of patients with typical biliary pain and
      normal ultrasound, with favourable outcomes following surgery.

PMID- 25588804
TI  - Nurse-administered intravitreal injections: a systematic review.

PMID- 25588805
TI  - DFT study of the molybdenum-catalyzed deoxydehydration of vicinal diols.
AB  - The mechanism of the molybdenum-catalyzed deoxydehydration (DODH) of vicinal
      diols has been investigated using density functional theory. The proposed
      catalytic cycle involves condensation of the diol with an Mo(VI) oxo complex,
      oxidative cleavage of the diol resulting in an Mo(IV) complex, and extrusion of
      the alkene. We have compared the proposed pathway with several alternatives, and
      the results have been corroborated by comparison with the molybdenum-catalyzed
      sulfoxide reduction recently published by Sanz et al. and with experimental
      observations for the DODH itself. Improved understanding of the mechanism should
      expedite future optimization of molybdenum-catalyzed biomass transformations. 

PMID- 25588806
TI  - Arabidopsis PED2 positively modulates plant drought stress resistance.
AB  - Abscisic acid (ABA) is an important phytohormone that functions in seed
      germination, plant development, and multiple stress responses. Arabidopsis
      Peroxisome defective 2 (AtPED2) (also known as AtPEXOXIN14, AtPEX14), is involved
      in the intracellular transport of thiolase from the cytosol to glyoxysomes, and
      perosisomal matrix protein import in plants. In this study, we assigned a new
      role for AtPED2 in drought stress resistance. The transcript level of AtPED2 was
      downregulated by ABA and abiotic stress treatments. AtPED2 knockout mutants were
      insensitive to ABA-mediated seed germination, primary root elongation, and
      stomatal response, while AtPED2 over-expressing plants were sensitive to ABA in
      comparison to wide type (WT). AtPED2 also positively regulated drought stress
      resistance, as evidenced by the changes of water loss rate, electrolyte leakage,
      and survival rate. Notably, AtPED2 positively modulated expression of several
      stress-responsive genes (RAB18, RD22, RD29A, and RD29B), positively affected
      underlying antioxidant enzyme activities and negatively regulated reactive oxygen
      species (ROS) level under drought stress conditions. Moreover, multiple carbon
      metabolites including amino acids, organic acids, sugars, sugar alcohols, and
      aromatic amines were also positively regulated by AtPED2. Taken together, these
      results indicated a positive role for AtPED2 in drought resistance, through
      modulation of stress-responsive genes expression, ROS metabolism, and metabolic
      homeostasis, at least partially.

PMID- 25588807
TI  - Vietnam's forest transition in retrospect: demonstrating weaknesses in business
      as-usual scenarios for REDD.
AB  - One of the prerequisites of the REDD+ mechanism is to effectively predict
      business-as-usual (BAU) scenarios for change in forest cover. This would enable
      estimation of how much carbon emission a project could potentially prevent and
      thus how much carbon credit should be rewarded. However, different factors like
      forest degradation and the lack of linearity in forest cover transitions
      challenge the accuracy of such scenarios. Here we predict and validate such BAU
      scenarios retrospectively based on forest cover changes at village and district
      level in North Central Vietnam. With the government's efforts to increase the
      forest cover, land use policies led to gradual abandonment of shifting
      cultivation since the 1990s. We analyzed Landsat images from 1973, 1989, 1998,
      2000, and 2011 and found that the policies in the areas studied did lead to
      increased forest cover after a long period of decline, but that this increase
      could mainly be attributed to an increase in open forest and shrub areas. We
      compared Landsat classifications with participatory maps of land cover/use in
      1998 and 2012 that indicated more forest degradation than was captured by the
      Landsat analysis. The BAU scenarios were heavily dependent on which years were
      chosen for the reference period. This suggests that hypothetical REDD+ activities
      in the past, when based on the remote sensing data available at that time, would
      have been unable to correctly estimate changes in carbon stocks and thus produce
      relevant BAU scenarios. 

PMID- 25588808
TI  - Modeling future land use scenarios in South Korea: applying the IPCC special
      report on emissions scenarios and the SLEUTH model on a local scale.
AB  - This study developed three scenarios of future land use/land cover on a local
      level for the Kyung-An River Basin and its vicinity in South Korea at a 30-m
      resolution based on the two scenario families of the Intergovernmental Panel on
      Climate Change (IPCC) Special Report Emissions Scenarios (SRES): A2 and B1, as
      well as a business-as-usual scenario. The IPCC SRES A2 and B1 were used to define
      future local development patterns and associated land use change. We quantified
      the population-driven demand for urban land use for each qualitative storyline
      and allocated the urban demand in geographic space using the SLEUTH model. The
      model results demonstrate the possible land use/land cover change scenarios for
      the years from 2000 to 2070 by examining the broad narrative of each SRES within
      the context of a local setting, such as the Kyoungan River Basin, constructing
      narratives of local development shifts and modeling a set of 'best guess'
      approximations of the future land use conditions in the study area. This study
      found substantial differences in demands and patterns of land use changes among
      the scenarios, indicating compact development patterns under the SRES B1 compared
      to the rapid and dispersed development under the SRES A2. 

PMID- 25588810
TI  - Polyamino acid display on cell surfaces enhances salt and alcohol tolerance of
      Escherichia coli.
AB  - Microbes employ cell membranes for reducing exogenous stresses. Polyamino acid
      display on microbial cell surfaces and their effects on microbial chemical stress
      tolerance were examined. Growth analysis revealed that displays of polyarginine,
      polyaspartate and polytryptophan substantially enhanced tolerance of Escherichia
      coli to NaCl. A titration assay indicated that polyarginine and polyaspartate
      altered cell surface charges, implying tolerance enhancement via ion atmosphere
      and/or ionic bond network formations for electrostatic ion repulsion. The
      enhancement by polytryptophan may have arisen from surface hydrophobicity
      increase for hydrophobic ion exclusion, because of a strong correlation between
      hydrophobic characters of amino acids and their effects on tolerance enhancement.
      The display also enhanced tolerance to other salts and/or alcohols in E. coli and
      to NaCl in Saccharomyces cerevisiae. Thus polyamino acid display has the
      potential as an approach for conferring chemical stress tolerance on various
      microbes. 

PMID- 25588809
TI  - Clinicopathological significance of nuclear factor (erythroid-2)-related factor 2
      (Nrf2) expression in gastric cancer.
AB  - BACKGROUND: The transcription factor nuclear factor (erythroid-2)-related factor
      2 (Nrf2) was originally identified as a critical regulator of intracellular anti
      oxidants and of phase II detoxification enzymes through its transcriptional up
      regulation of many anti-oxidant response element (ARE)-containing genes. Nrf2
      protects not only normal cells but also cancer cells from cellular stress, and
      enhances cancer cell survival. Some studies have shown that Nrf2 expression in
      cancer patients has clinical significance. However, there has been no
      comprehensive analysis of the nuclear expression level of Nrf2 in
      gastrointestinal cancer cells. In this study we aimed to immunohistochemically
      evaluate the expression of Nrf2, and to assess its clinical significance in
      gastric cancer. METHODS: A total of 175 gastric cancer patients who received R0
      gastrectomy with standard lymph node dissection were enrolled. We
      immunohistochemically evaluated Nrf2 expression in the paraffin-embedded
      surgically resected specimens of these 175 patients. Group differences were
      analyzed using the chi (2) test, Fisher's exact test, and the Mann-Whitney U
      test. Associations between Nrf2 expression and clinicopathological features,
      including clinical outcome, were assessed using univariate and multivariate
      analyses, and Kaplan-Meier curves with the log-rank test, respectively. RESULTS:
      Nrf2 immunoreactivity was predominantly identified in the nucleus of gastric
      cancer cells. Nrf2 positivity was closely associated with tumor size, tumor
      depth, lymph node metastases, lymphovascular invasion, histology and stage (p <
      0.05 for all). A log-rank test indicated that the overall survival of the Nrf2
      positive group was significantly poorer than that of the Nrf2-negative group (p <
      0.01). And, positive Nrf2 expression was significantly associated with resistance
      to 5FU-based adjuvant chemotherapy (p = 0.024). CONCLUSIONS: Nrf2 expression was
      positively associated with aggressive tumor behavior in gastric cancer. This
      result suggests that Nrf2 expression in gastric cancer is a potential indicator
      of worse prognosis.

PMID- 25588811
TI  - Enhanced charge separation in ternary P3HT/PCBM/CuInS2 nanocrystals hybrid solar
      cells.
AB  - Geminate recombination of bound polaron pairs at the donor/acceptor interface is
      one of the major loss mechanisms in organic bulk heterojunction solar cells. One
      way to overcome Coulomb attraction between opposite charge carriers and to
      achieve their full dissociation is the introduction of high dielectric
      permittivity materials such as nanoparticles of narrow band gap semiconductors.
      We selected CuInS2 nanocrystals of 7.4 nm size, which present intermediate energy
      levels with respect to poly(3-hexylthiophene) (P3HT) and Phenyl-C61-butyric acid
      methyl ester (PCBM). Efficient charge transfer from P3HT to nanocrystals takes
      place as evidenced by light-induced electron spin resonance. Charge transfer
      between nanocrystals and PCBM only occurs after replacing bulky dodecanethiol
      (DDT) surface ligands with shorter 1,2-ethylhexanethiol (EHT) ligands. Solar
      cells containing in the active layer a ternary blend of P3HT:PCBM:CuInS2-EHT
      nanocrystals in 1:1:0.5 mass ratio show strongly improved short circuit current
      density and a higher fill factor with respect to the P3HT:PCBM reference device.
      Complementary measurements of the absorption properties, external quantum
      efficiency and charge carrier mobility indicate that enhanced charge separation
      in the ternary blend is at the origin of the observed behavior. The same trend is
      observed for blends using the glassy polymer poly(triarylamine) (PTAA).

PMID- 25588812
TI  - Glial beta-oxidation regulates Drosophila energy metabolism.
AB  - The brain's impotence to utilize long-chain fatty acids as fuel, one of the
      dogmas in neuroscience, is surprising, since the nervous system is the tissue
      most energy consuming and most vulnerable to a lack of energy. Challenging this
      view, we here show in vivo that loss of the Drosophila carnitine
      palmitoyltransferase 2 (CPT2), an enzyme required for mitochondrial beta
      oxidation of long-chain fatty acids as substrates for energy production, results
      in the accumulation of triacylglyceride-filled lipid droplets in adult Drosophila
      brain but not in obesity. CPT2 rescue in glial cells alone is sufficient to
      restore triacylglyceride homeostasis, and we suggest that this is mediated by the
      release of ketone bodies from the rescued glial cells. These results demonstrate
      that the adult brain is able to catabolize fatty acids for cellular energy
      production. 

PMID- 25588813
TI  - Evaluating the association between CACNA1C rs1006737 and schizophrenia risk: A
      meta-analysis.
AB  - INTRODUCTION: Genetic analyses including genome-wide association studies have
      reported an intronic single nucleotide polymorphism (SNP) rs1006737 in CACNA1C
      gene (encoded calcium channel, voltage-dependent, L type, alpha 1C subunit) as a
      risk factor for schizophrenia in European populations. The replications in other
      ethnic populations such as East Asians have also been conducted, but the results
      were inconsistent, either likely due to the limited sample size of single study
      or genetic heterogeneity between continental populations on this locus. METHODS:
      We performed a comprehensive meta-analysis of all available samples from existing
      studies of East Asian populations, including a total of 9,432 cases and 10,661
      controls, to further confirm whether CACNA1C rs1006737 is an authentic risk SNP
      for schizophrenia in East Asian populations. RESULTS: Our results revealed a
      significant association between rs1006737 and schizophrenia (allelic model, P =
      4.39 * 10(-6) , pooled odds ratio [OR] = 1.20), and the results were much
      strengthened when the European and East Asian samples were combined together (P =
      2.40 * 10(-17) , pooled OR = 1.12). There is no significant heterogeneity or
      publication bias between individual studies, and removal of any single study
      still remained significant associations between rs1006737 and schizophrenia.
      DISCUSSION: Our results further confirmed that rs1006737 should be categorized as
      an authentic risk SNP for schizophrenia in the general populations.

PMID- 25588814
TI  - Longitudinal associations between cyber-bullying perpetration and victimization
      and problem behavior and mental health problems in young Australians.
AB  - OBJECTIVES: To investigate associations between Grade 9 and 10 cyber-bullying
      perpetration and victimization and Grade 11 problem behavior and mental health
      problems after controlling for risk factors for these outcomes in the analyses.
      METHODS: The sample comprised 927 students from Victoria, Australia who completed
      a modified version of the self-report Communities That Care Youth Survey in
      Grades 9-11 to report on risk factors, traditional and cyber-bullying
      perpetration and victimization, problem behavior, and mental health. Complete
      data on over 650 participants were analyzed. RESULTS: Five per cent of Grade 9
      and 10 students reported cyber-bullying perpetration only, 6-8% reported
      victimization only, and 8-9% both cyber-bullied others and were cyber-bullied.
      Results showed that cyber-bullying others in Grade 10 was associated with theft
      in Grade 11, cyber-victimization in Grade 10 was linked with Grade 11 depressive
      symptoms, and Grade 10 cyber-bullying perpetration and victimization combined
      predicted Grade 11 school suspension and binge drinking. CONCLUSIONS: Prevention
      approaches that target traditional and cyber-bullying, and established risk
      factors are necessary. Such multi-faceted programs may also reduce problem
      behavior and mental health problems.

PMID- 25588816
TI  - Image Integration of Coronary Cine-Angiography with 3D Electroanatomic Mapping
      Using CartoUnivu for Left Coronary Cusp Ventricular Tachycardia.

PMID- 25588815
TI  - Stillbirth in an Anglophone minority of Canada.
AB  - OBJECTIVES: We assessed trends in stillbirth over time for Francophones and
      Anglophones of Quebec, a large Canadian province with publically funded health
      care and an English-speaking minority. METHODS: We calculated stillbirth rates
      for Francophones and Anglophones, and estimated hazard ratios (HR) by decade from
      1981 to 2010, adjusting for maternal characteristics. We analyzed temporal trends
      by gestational interval and cause of fetal death. RESULTS: Stillbirth rates
      decreased in Quebec during the three decades, due to improved rates in
      Francophones. Rates decreased for Anglophones in 1991-2000, but increased in 2001
      2010 at term, during the second trimester, and for most causes of fetal death. In
      the 2000s, the hazard of stillbirth for Anglophones was nearly the same as the
      hazard for Francophones in the 1980s (HR 0.93, 95 % confidence interval 0.82,
      1.05). CONCLUSIONS: Stillbirth rates declined in both Francophones and
      Anglophones before the turn of the century, but increased thereafter for
      Anglophones, suggesting that linguistic inequalities in stillbirth may be
      emerging in Quebec. Linguistic status may be a useful marker for surveillance of
      inequalities in stillbirth.

PMID- 25588817
TI  - Human 3-hydroxyanthranilate 3,4-dioxygenase () dynamics and reaction, a
      multilevel computational study.
AB  - 3-Hydroxyanthranilate 3,4-dioxygenase () is a non-heme iron dependent enzyme. It
      catalyses the cleavage of the benzene ring of 3-hydroxyanthranilic acid (3-Ohaa),
      an intermediate in the kynurenine pathway, and therefore represents a potential
      target in treating numerous disorders related to the concentration of quinolinic
      acid (QUIN), the kynurenine pathway product, in tissues. The stability and
      behaviour of the enzyme in nearly physiological conditions, studied by the
      empirical molecular modelling methods enabled us to determine the influence of
      several, for the enzyme activity relevant, point mutations (Arg43Ala, Arg95Ala
      and Glu105Ala) on the protein structure, particularly on the active site
      architecture and the metal ion environment, as well as on the substrate, 3-Ohaa,
      binding. Besides, the water population of the active site, and the protein
      flexibility as well as the amino acid residues interaction networks relevant for
      the enzyme activity were determined for the 3-Ohaa complexes with the native and
      mutated enzyme variants. Finally, using the hybrid quantum-mechanics/molecular
      mechanics (QM/MM) calculations the catalysed 3-Ohaa oxidation into 2-amino-3
      carboxymuconic acid semialdehyde was elucidated. 

PMID- 25588818
TI  - Open your eyes for prediction errors.
AB  - Previous studies have demonstrated that autonomic arousal is increased following
      correct task performance on a difficult, relative to an easy, task. Here, we
      hypothesized that this arousal response reflects the (relative) surprise of
      correct performance following a difficult versus an easy task. Following this
      line of reasoning, we would expect to find a reversed pattern following erroneous
      responses, because errors are less expected during an easy than during a
      difficult task. To test this, participants performed a flanker task while pupil
      size was measured online. As predicted, the results demonstrated that pupil size
      was larger following difficult (incongruent) correct trials than following easy
      (congruent) correct trials, but smaller following difficult than following easy
      incorrect trials. Moreover, participants with larger congruency effects, and
      hence a larger difference in outcome expectancies between the two trial types,
      showed larger differences in pupil size after both correct and incorrect
      responses, further corroborating the idea that pupil size increased as a measure
      of performance prediction errors. 

PMID- 25588819
TI  - Validity of the Acti4 method for detection of physical activity types in free
      living settings: comparison with video analysis.
AB  - This study examined the ability of the Acti4 software for identifying physical
      activity types from accelerometers during free-living with different levels of
      movement complexity compared with video observations. Nineteen aircraft cabin
      cleaners with ActiGraph GT3X+ accelerometer at the thigh and hip performed one
      semi-standardised and two non-standardised sessions (outside and inside aircraft)
      with different levels of movement complexity during working hours. The
      sensitivity for identifying different activity types was 75.4-99.4% for the semi
      standardised session, 54.6-98.5% outside the aircraft and 49.9-90.2% inside the
      aircraft. The specificity was above 90% for all activities, except 'moving'
      inside the aircraft. These findings indicate that Acti4 provides good estimates
      of time spent in different activity types during semi-standardised conditions,
      and for sitting, standing and walking during non-standardised conditions with
      normal level of movement complexity. The Acti4 software may be a useful tool for
      researchers and practitioners in the field of ergonomics, occupational and public
      health. Practitioner Summary: Being inexpensive, small, water-resistant and
      without wires, the ActiGraph GT3X+ by applying the Acti4 software may be a useful
      tool for long-term field measurements of physical activity types for researchers
      and practitioners in the field of ergonomics, occupational and public health. 

PMID- 25588821
TI  - Characterization of monoclonal antibodies against duck Tembusu virus E protein:
      an antigen-capture ELISA for the detection of Tembusu virus infection.
AB  - The E protein of flaviviruses is the primary antigen that induces protective
      immunity, but a monoclonal antibody (mAb) against the E protein of duck Tembusu
      virus (DTMUV) has never been characterized. Six hybridoma cell lines secreting
      DTMUV anti-E mAbs were prepared and designated 2A5, 1F3, 1G2, 1B11, 3B6, and 4F9,
      respectively. An immunofluorescence assay indicated that the mAbs could
      specifically bind to duck embryo fibroblast (DEF) cells infected with DTMUV and
      that the E protein was distributed in the cytoplasm of the infected cells.
      Immunoglobulin isotyping differentiated the mAbs as IgG1 (1G2, 1B11, 4F9, 1F3,
      and 2A5) and IgG2b (3B6). The mAbs were used to identify three epitopes, A (2A5,
      1F3, and 1G2), B (1B11 and 4F9), and C (3B6) on the E protein on the basis of a
      competitive binding assay. By using mAbs 1F3 and 3B6, we developed an antigen
      capture enzyme-linked immunosorbent assay (AC-ELISA) to detect E antigen from
      clinical samples. The AC-ELISA did not react with other known pathogens,
      indicating that the mAbs are specific for DTMUV. Compared to RT-PCR, the
      specificity and sensitivity of the AC-ELISA was 94.1 % and 98.0 %, respectively.
      This AC-ELISA thus represents a sensitive and rapid method for detecting DTMUV
      infection in birds.

PMID- 25588820
TI  - Enrichment of human hematopoietic stem/progenitor cells facilitates transduction
      for stem cell gene therapy.
AB  - Autologous hematopoietic stem cell (HSC) gene therapy for sickle cell disease has
      the potential to treat this illness without the major immunological complications
      associated with allogeneic transplantation. However, transduction efficiency by
      beta-globin lentiviral vectors using CD34-enriched cell populations is suboptimal
      and large vector production batches may be needed for clinical trials.
      Transducing a cell population more enriched for HSC could greatly reduce vector
      needs and, potentially, increase transduction efficiency. CD34(+) /CD38(-) cells,
      comprising ~1%-3% of all CD34(+) cells, were isolated from healthy cord blood
      CD34(+) cells by fluorescence-activated cell sorting and transduced with a
      lentiviral vector expressing an antisickling form of beta-globin (CCL-beta(AS3) 
      FB). Isolated CD34(+) /CD38(-) cells were able to generate progeny over an
      extended period of long-term culture (LTC) compared to the CD34(+) cells and
      required up to 40-fold less vector for transduction compared to bulk CD34(+)
      preparations containing an equivalent number of CD34(+) /CD38(-) cells.
      Transduction of isolated CD34(+) /CD38(-) cells was comparable to CD34(+) cells
      measured by quantitative PCR at day 14 with reduced vector needs, and average
      vector copy/cell remained higher over time for LTC initiated from CD34(+) /38(-)
      cells. Following in vitro erythroid differentiation, HBBAS3 mRNA expression was
      similar in cultures derived from CD34(+) /CD38(-) cells or unfractionated CD34(+)
      cells. In vivo studies showed equivalent engraftment of transduced CD34(+) /CD38(
      ) cells when transplanted in competition with 100-fold more CD34(+) /CD38(+)
      cells. This work provides initial evidence for the beneficial effects from
      isolating human CD34(+) /CD38(-) cells to use significantly less vector and
      potentially improve transduction for HSC gene therapy.

PMID- 25588822
TI  - To Forgive and Discredit: Bipolar Identities and Medicated Selves Among Female
      Youth in Residential Treatment.
AB  - Based on 11 months of ethnographic fieldwork at a residential treatment center in
      the United States, this article explores the varied meanings that female youth
      attribute to behavior and the strategic (mis)use of knowledge about psychiatric
      diagnosis and medication at a time when the scope of behaviors pathologized in
      young people continues to expand. Drawing upon psychological and critically
      applied medical anthropology, as well as contributions from philosophy on how
      classifications of people come into being and circulate, attention is paid to the
      multiple contradictions at work in diagnosing young people with mental disorders.
      A detailed examination of an exchange that occurred during one particular group
      therapy session is presented to demonstrate how psychiatric selves emerge in this
      environment when conventional labeling practices no longer suffice as an
      explanation of behavior. This turn to psychiatry reveals both the salience of and
      confusion around mental health treatment and diagnosis among adolescents, opens
      up the distinctions young people make between "real selves" and "medicated
      selves," and invokes the possibility of psychiatric disorder as a means to both
      forgive and discredit.

PMID- 25588823
TI  - Sports-related eye injuries: the current picture.
AB  - PURPOSE: This study aims to represent the epidemiologies, findings, treatments,
      use of resources, outcomes and protective-eyewear-use recommendations in sports
      related eye injuries by sport type. METHODS: The study population is comprised of
      all new eye injury patients in 1 year in Helsinki University Eye Hospital. Data
      were collected from patient questionnaires and hospital records. The follow-up
      period was 3 months. RESULTS: 149/1151 (12.9%) of eye injuries were sports
      related. Thirty two percent were related to floorball (type of hockey played on a
      mat with a stick and a ball); football, tennis and ice hockey were the next most
      common eye-injury-causing sports. Relatively, the most dangerous sports were rink
      bandy, (bandy played on ice hockey rink with a stick and a ball) (0.50 injuries
      in 12 months/1000 participants, CI 0.10-1.46), floorball (0.47, CI 0.34-0.62) and
      tennis (0.47, CI 0.26-0.77). Contusion was the primary diagnosis in 77% of cases;
      41% of contusion patients had severe, mainly retinal findings. The number of
      outpatient visits was 459; inpatient days 25 and major surgeries 31. One hundred
      and eight patients were estimated to need life-long follow-up. Seventeen patients
      had a permanent functional impairment, 4 in ice hockey, 3 in floorball, 2 each in
      tennis and badminton. CONCLUSION: Compared to a previous study, ice hockey eye
      injuries are increasing and relatively severe, and a third of these injuries
      occurred despite visor use. Floorball eye injury incidence has significantly
      declined, mainly due to recently enforced mandatory protective eyewear for
      younger age groups. Based on these findings, we recommend, in floorball, that
      protective eyewear should be mandatory in all age groups. Universally in ice
      hockey, the proper use of a visor should be emphasised.

PMID- 25588824
TI  - Unlocking the sost gene.

PMID- 25588825
TI  - An orthodontic bracket embedded in the medial pterygoid surface: a case report.
AB  - There is a potential risk that orthodontic brackets can become dislodged into the
      aerodigestive tract. This case illustrates the management of an orthodontic
      bracket, which became embedded in the deep tissues of the oropharynx. We aim to
      highlight the potential risk misplaced dental instruments and materials pose,
      including that they may become embedded in the soft tissues of the throat and
      suggest that that this possibility should be considered when they cannot be
      localized. 

PMID- 25588826
TI  - Applicability of the Tanaka-Johnston and Moyers mixed dentition analyses in
      Northeast Han Chinese.
AB  - OBJECTIVES: To assess applicability of the Tanaka-Johnston and Moyers prediction
      methods in a Han ethnic group from Northeast China and to develop prediction
      equations for this same population. DESIGN: Cross-sectional study. SETTING:
      Department of Orthodontics, School of Stomatology, Jiamusi University,
      Heilongjiang, China. PARTICIPANTS: A total of 130 subjects (65 male and 65
      female) aged 16-21 years from a Han ethnic group of Northeast China were
      recruited from dental students and patients seeking orthodontic treatment.
      Ethnicity was verified by questionnaire. MATERIAL AND METHODS: Mesio-distal tooth
      width was measured using Digital Vernier calipers. Predicted values were obtained
      from the Tanaka-Johnston and Moyers methods in both arches were compared with the
      actual measured widths. Based on regression analysis, prediction equations were
      developed. RESULTS: Tanaka-Johnston equations were not precise, except for the
      upper arch in males. However, the Moyers 85th percentile in the upper arch and
      75th percentile in the lower arch predicted the sum precisely in males. For
      females, the Moyers 75th percentile predicted the sum precisely for the upper
      arch, but none of the Moyers percentiles predicted in the lower arch.
      CONCLUSIONS: Both the Tanaka-Johnston and Moyers method may not be applied
      universally without question. Hence, it may be safer to develop regression
      equations for specific populations. Validating studies must be conducted to
      confirm the precision of these newly developed regression equations.

PMID- 25588827
TI  - Actual versus theoretical torsional play in conventional and self-ligating
      bracket systems.
AB  - OBJECTIVE: The aim of this study was to assess the amount of torsional play in 32
      commercially available self-ligating and conventional 0.018-inch and 0.022-inch
      bracket systems in relation to 0.017*0.022-inch and 0.019*0.025-inch stainless
      steel wires, respectively, and compare the results with the theoretical amount of
      play for the given bracket/wire combinations. METHODS: Torque moments were
      measured in a mechanical force testing system by twisting straight pieces of
      stainless steel wire seated in the bracket slot in increments of 0.5 degrees 
      until a full torsional expression was registered. Five upper central incisor
      brackets from each of the 32 different bracket systems were selected for the
      study. RESULTS: The result from the laboratory testing clearly showed that
      wire/slot play was larger than anticipated from the nominal values, especially
      regarding the 0.022-inch brackets and particularly in relation to the passive
      self-ligating brackets. The play ranged from 19.8 to 36.1 degrees  of play for
      the most imprecise bracket system. CONCLUSIONS: The result does not favour the
      use of self-ligating brackets when focussing on torque control. The actual play
      is larger due to oversized slots and the inability of self-ligation brackets to
      press the archwire into the bottom of the slot. In conventional brackets, the
      initial torque moment is generated by the steel ligatures pressing the arch wire
      against the bottom of the slot. The oversize of the slot is thus less critical in
      relation to the conventional than in relation to the passive self-ligation
      bracket.

PMID- 25588828
TI  - How patient and carer expectations of orthodontic treatment vary with ethnicity.
AB  - OBJECTIVE: To investigate if the orthodontic treatment expectations of Black
      British children and their primary carers vary compared with White British
      children and their primary carers. SETTING: A hospital orthodontic department
      (Queen Mary's Hospital, Sidcup, London, UK). PARTICIPANTS: Patients and their
      accompanying primary carers who had not received fixed orthodontic appliance
      treatment and were aged between 12 and 14 years old. METHOD: Informed consent was
      obtained from 100 patients and their primary carers, who completed a
      psychometrically validated questionnaire, to measure their expectations before a
      new patient orthodontic consultation. This cohort consisted of 50 Black British
      patients and their primary carers and 50 White British patients and their primary
      carers. RESULTS: Mean responses from patients and their primary carers for each
      ethnic group were compared using the independent groups t-test. Significant
      statistical differences were found between the two ethnic groups. The greatest
      statistical differences occurred between Black British patients and their primary
      carer and Black British primary carers and White British primary carers. Patients
      tended to have similar orthodontic expectations. There were no statistical
      significant differences in expectations between White British children and their
      primary carers. CONCLUSION: Differences in expectations of orthodontic treatment
      were more common between Black British and White British primary carers, than
      their children. White British primary carers had higher expectations at their
      child's initial appointment and expected dental extractions to be part of the
      orthodontic treatment plan. These differences have some implications for the
      provision of orthodontic care. A clinicians understanding of patients and their
      primary carer's expectations at the start of treatment can help in the quality
      and delivery of orthodontic care provided.

PMID- 25588830
TI  - SEPT12 orchestrates the formation of mammalian sperm annulus by organizing core
      octameric complexes with other SEPT proteins.
AB  - Male infertility has become a worldwide health problem, but the etiologies of
      most cases are still unknown. SEPT12, a GTP-binding protein, is involved in male
      fertility. Two SEPT12 mutations (SEPT12(T89M) and SEPT12(D197N)) have been
      identified in infertile men who have a defective sperm annulus with a bent tail.
      The function of SEPT12 in the sperm annulus is still unclear. Here, we found that
      SEPT12 formed a filamentous structure with SEPT7, SEPT 6, SEPT2 and SEPT4 at the
      sperm annulus. The SEPT12-based septin core complex was assembled as octameric
      filaments comprising the SEPT proteins 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7-12. In
      addition, the GTP-binding domain of SEPT12 was crucial for its interaction with
      SEPT7, and the N- and C-termini of SEPT12 were required for the interaction of
      SEPT12 with itself to polymerize octamers into filaments. Mutant mice carrying
      the SEPT12(D197N) mutation, which disrupts SEPT12 filament formation, showed a
      disorganized sperm annulus, bent tail, reduced motility and loss of the SEPT ring
      structure at the sperm annulus. These phenotypes were also observed in an
      infertile man carrying SEPT12(D197N). Taken together, our results demonstrate the
      molecular architecture of SEPT12 filaments at the sperm annulus, their mechanical
      support of sperm motility, and their correlation with male infertility. 

PMID- 25588829
TI  - Acetylation of the RhoA GEF Net1A controls its subcellular localization and
      activity.
AB  - Net1 isoform A (Net1A) is a RhoA GEF that is required for cell motility and
      invasion in multiple cancers. Nuclear localization of Net1A negatively regulates
      its activity, and we have recently shown that Rac1 stimulates Net1A
      relocalization to the plasma membrane to promote RhoA activation and cytoskeletal
      reorganization. However, mechanisms controlling the subcellular localization of
      Net1A are not well understood. Here, we show that Net1A contains two nuclear
      localization signal (NLS) sequences within its N-terminus and that residues
      surrounding the second NLS sequence are acetylated. Treatment of cells with
      deacetylase inhibitors or expression of active Rac1 promotes Net1A acetylation.
      Deacetylase inhibition is sufficient for Net1A relocalization outside the
      nucleus, and replacement of the N-terminal acetylation sites with arginine
      residues prevents cytoplasmic accumulation of Net1A caused by deacetylase
      inhibition or EGF stimulation. By contrast, replacement of these sites with
      glutamine residues is sufficient for Net1A relocalization, RhoA activation and
      downstream signaling. Moreover, the N-terminal acetylation sites are required for
      rescue of F-actin accumulation and focal adhesion maturation in Net1 knockout
      MEFs. These data indicate that Net1A acetylation regulates its subcellular
      localization to impact on RhoA activity and actin cytoskeletal organization. 

PMID- 25588832
TI  - Dimerization drives EGFR endocytosis through two sets of compatible endocytic
      codes.
AB  - We have shown previously that epidermal growth factor (EGF) receptor (EGFR)
      endocytosis is controlled by EGFR dimerization. However, it is not clear how the
      dimerization drives receptor internalization. We propose that EGFR endocytosis is
      driven by dimerization, bringing two sets of endocytic codes, one contained in
      each receptor monomer, in close proximity. Here, we tested this hypothesis by
      generating specific homo- or hetero-dimers of various receptors and their
      mutants. We show that ErbB2 and ErbB3 homodimers are endocytosis deficient owing
      to the lack of endocytic codes. Interestingly, EGFR-ErbB2 or EGFR-ErbB3
      heterodimers are also endocytosis deficient. Moreover, the heterodimer of EGFR
      and the endocytosis-deficient mutant EGFRDelta1005-1017 is also impaired in
      endocytosis. These results indicate that two sets of endocytic codes are required
      for receptor endocytosis. We found that an EGFR-PDGFRbeta heterodimer is
      endocytosis deficient, although both EGFR and PDGFRbeta homodimers are
      endocytosis-competent, indicating that two compatible sets of endocytic codes are
      required. Finally, we found that to mediate the endocytosis of the receptor
      dimer, the two sets of compatible endocytic codes, one contained in each receptor
      molecule, have to be spatially coordinated. 

PMID- 25588833
TI  - Cavin3 interacts with cavin1 and caveolin1 to increase surface dynamics of
      caveolae.
AB  - Caveolae are invaginations of the cell surface thought to regulate membrane
      tension, signalling, adhesion and lipid homeostasis owing to their dynamic
      behaviour ranging from stable surface association to dynamic rounds of fission
      and fusion with the plasma membrane. The caveolae coat is generated by
      oligomerisation of the membrane protein caveolin and the family of cavin
      proteins. Here, we show that cavin3 (also known as PRKCDBP) is targeted to
      caveolae by cavin1 (also known as PTRF) where it interacts with the scaffolding
      domain of caveolin1 and promote caveolae dynamics. We found that the N-terminal
      region of cavin3 binds a trimer of the cavin1 N-terminus in competition with a
      homologous cavin2 (also known as SDPR) region, showing that the cavins form
      distinct subcomplexes through their N-terminal regions. Our data shows that
      cavin3 is enriched at deeply invaginated caveolae and that loss of cavin3 in
      cells results in an increase of stable caveolae and a decrease of caveolae that
      are only present at the membrane for a short time. We propose that cavin3 is
      recruited to the caveolae coat by cavin1 to interact with caveolin1 and regulate
      the duration time of caveolae at the plasma membrane. 

PMID- 25588834
TI  - Brca2-Pds5 complexes mobilize persistent meiotic recombination sites to the
      nuclear envelope.
AB  - Homologous recombination is required for reciprocal exchange between homologous
      chromosome arms during meiosis. Only select meiotic recombination events become
      chromosomal crossovers; the majority of recombination outcomes are noncrossovers.
      Growing evidence suggests that crossovers are repaired after noncrossovers. Here,
      I report that persisting recombination sites are mobilized to the nuclear
      envelope of Drosophila pro-oocytes during mid-pachytene. Their number correlates
      with the average crossover rate per meiosis. Proteomic and interaction studies
      reveal that the recombination mediator Brca2 associates with lamin and the
      cohesion factor Pds5 to secure persistent recombination sites at the nuclear
      envelope. In Rad51(-/-) females, all persistent DNA breaks are directed to the
      nuclear envelope. By contrast, a reduction of Pds5 or Brca2 levels abolishes the
      movement and has a negative impact on crossover rates. The data suggest that
      persistent meiotic DNA double-strand breaks might correspond to crossovers, which
      are mobilized to the nuclear envelope for their repair. The identification of
      Brca2-Pds5 complexes as key mediators of this process provides a first
      mechanistic explanation for the contribution of lamins and cohesins to meiotic
      recombination.

PMID- 25588831
TI  - The heterotrimeric kinesin-2 complex interacts with and regulates GLI protein
      function.
AB  - GLI transport to the primary cilium and nucleus is required for proper Hedgehog
      (HH) signaling; however, the mechanisms that mediate these trafficking events are
      poorly understood. Kinesin-2 motor proteins regulate ciliary transport of cargo,
      yet their role in GLI protein function remains unexplored. To examine a role for
      the heterotrimeric KIF3A-KIF3B-KAP3 kinesin-2 motor complex in regulating GLI
      activity, we performed a series of structure-function analyses using biochemical,
      cell signaling and in vivo approaches that define novel specific interactions
      between GLI proteins and two components of this complex, KAP3 and KIF3A. We find
      that all three mammalian GLI proteins interact with KAP3 and we map specific
      interaction sites in both proteins. Furthermore, we find that GLI proteins
      interact selectively with KIF3A, but not KIF3B, and that GLI interacts
      synergistically with KAP3 and KIF3A. Using a combination of cell signaling assays
      and chicken in ovo electroporation, we demonstrate that KAP3 interactions
      restrict GLI activator function but not GLI repressor function. These data
      suggest that GLI interactions with KIF3A-KIF3B-KAP3 complexes are essential for
      proper GLI transcriptional activity. 

PMID- 25588835
TI  - Cell competition in mouse NIH3T3 embryonic fibroblasts is controlled by the
      activity of Tead family proteins and Myc.
AB  - Cell competition is a short-range communication originally observed in
      Drosophila. Relatively little is known about cell competition in mammals or in
      non-epithelial cells. Hippo signaling and its downstream transcription factors of
      the Tead family, control cell proliferation and apoptosis. Here, we established
      an in vitro model system that shows cell competition in mouse NIH3T3 embryo
      fibroblast cells. Co-culture of Tead-activity-manipulated cells with normal (wild
      type) cells caused cell competition. Cells with reduced Tead activity became
      losers, whereas cells with increased Tead activity became super-competitors. Tead
      directly regulated Myc RNA expression, and cells with increased Myc expression
      also became super-competitors. At low cell density, cell proliferation required
      both Tead activity and Myc. At high cell density, however, reduction of either
      Tead activity or Myc was compensated for by an increase in the other, and this
      increase was sufficient to confer 'winner' activity. Collectively, NIH3T3 cells
      have cell competition mechanisms similar to those regulated by Yki and Myc in
      Drosophila. Establishment of this in vitro model system should be useful for
      analyses of the mechanisms of cell competition in mammals and in fibroblasts. 

PMID- 25588837
TI  - Loss of LKB1 leads to impaired epithelial integrity and cell extrusion in the
      early mouse embryo.
AB  - LKB1/PAR-4 is essential for the earliest polarization steps in Caenorhabditis
      elegans embryos and Drosophila oocytes. Although LKB1 (also known as STK11) is
      sufficient to initiate polarity in a single mammalian intestinal epithelial cell,
      its necessity in the formation and maintenance of mammalian epithelia remains
      unclear. To address this, we completely remove LKB1 from mouse embryos by
      generating maternal-zygotic Lkb1 mutants and find that it is dispensable for
      polarity and epithelia formation in the early embryo. Instead, loss of Lkb1 leads
      to the extrusion of cells from blastocyst epithelia that remain alive and can
      continue to divide. Chimeric analysis shows that Lkb1 is cell-autonomously
      required to prevent these extrusions. Furthermore, heterozygous loss of Cdh1
      exacerbates the number of extrusions per blastocyst, suggesting that LKB1 has a
      role in regulating adherens junctions in order to prevent extrusion in epithelia.

PMID- 25588836
TI  - Specific interaction of KIF11 with ZBP1 regulates the transport of beta-actin
      mRNA and cell motility.
AB  - ZBP1-modulated localization of beta-actin mRNA enables a cell to establish
      polarity and structural asymmetry. Although the mechanism of beta-actin mRNA
      localization has been well established, the underlying mechanism of how a
      specific molecular motor contributes to the transport of the ZBP1 (also known as
      IGF2BP1) complex in non-neuronal cells remains elusive. In this study, we report
      the isolation and identification of KIF11, a microtubule motor, which physically
      interacts with ZBP1 and is a component of beta-actin messenger ribonucleoprotein
      particles (mRNPs). We show that KIF11 colocalizes with the beta-actin mRNA, and
      the ability of KIF11 to transport beta-actin mRNA is dependent on ZBP1. We
      characterize the corresponding regions of ZBP1 and KIF11 that mediate the
      interaction of the two proteins in vitro and in vivo. Disruption of the in vivo
      interaction of KIF11 with ZBP1 delocalizes beta-actin mRNA and affects cell
      migration. Our study reveals a molecular mechanism by which a particular
      microtubule motor mediates the transport of an mRNP through direct interaction
      with an mRNA-binding protein. 

PMID- 25588838
TI  - PDK1 regulates focal adhesion disassembly by modulating endocytosis of
      alphavbeta3 integrin.
AB  - Non-amoeboid cell migration is characterised by dynamic competition among
      multiple protrusions to establish new adhesion sites at the cell's leading edge.
      However, the mechanisms that regulate the decision to disassemble or to grow
      nascent adhesions are not fully understood. Here we show that, in endothelial
      cells, 3-phosphoinositide-dependent protein kinase 1 (PDK1) promotes focal
      adhesion (FA) turnover by controlling endocytosis of integrin alphavbeta3 in a
      PI3K-dependent manner. We demonstrate that PDK1 binds and phosphorylates integrin
      alphavbeta3. Downregulation of PDK1 increases FA size and slows down their
      disassembly. This process requires both PDK1 kinase activity and PI3K activation
      but does not involve Akt. Moreover, PDK1 silencing stabilises FA in membrane
      protrusions decreasing migration of endothelial cells on vitronectin. These
      results indicate that modulation of integrin endocytosis by PDK1 hampers
      endothelial cell adhesion and migration on extracellular matrix, thus unveiling a
      novel role for this kinase. 

PMID- 25588840
TI  - TOM1 is a PI5P effector involved in the regulation of endosomal maturation.
AB  - Phosphoinositides represent a major class of lipids specifically involved in the
      organization of signaling cascades, maintenance of the identity of organelles and
      regulation of multiple intracellular trafficking steps. We previously reported
      that phosphatidylinositol 5-monophosphate (PI5P), produced by the Shigella
      flexneri phosphatase IpgD, is implicated in the endosomal sorting of the
      epidermal growth factor receptor (EGFR). Here, we show that the adaptor protein
      TOM1 is a new direct binding partner of PI5P. We identify the domain of TOM1
      involved in this interaction and characterize the binding motif. Finally, we
      demonstrate that the recruitment of TOM1 by PI5P on signaling endosomes is
      responsible for the delay in EGFR degradation and fluid-phase bulk endocytosis.
      Taken together, our data strongly suggest that PI5P enrichment in signaling
      endosomes prevents endosomal maturation through the recruitment of TOM1, and
      point to a new function of PI5P in regulating discrete maturation steps in the
      endosomal system. 

PMID- 25588839
TI  - IQGAP1 controls tight junction formation through differential regulation of
      claudin recruitment.
AB  - IQGAP1 is a scaffolding protein previously implicated in adherens junction
      formation. However, its role in the establishment or maintenance of tight
      junctions (TJs) has not been explored. We hypothesized that IQGAP1 could regulate
      TJ formation by modulating the expression and/or localization of junctional
      proteins, and we systematically tested this hypothesis in the model Madin-Darby
      canine kidney (MDCK) cell line. We find that IQGAP1 silencing enhances a
      transient increase in transepithelial electrical resistance (TER) observed during
      the early stages of TJ formation (Cereijido et al., 1978). Quantitative
      microscopy and biochemical experiments suggest that this effect of IQGAP1 on TJ
      assembly is accounted for by reduced expression and TJ recruitment of claudin 2,
      and increased TJ recruitment of claudin 4. Furthermore, we show that IQGAP1 also
      regulates TJ formation through its interactor CDC42, because IQGAP1 knockdown
      increases the activity of the CDC42 effector JNK and dominant-negative CDC42
      prevents the increase in TER caused by IQGAP1 silencing. Hence, we provide
      evidence that IQGAP1 modulates TJ formation by a twofold mechanism: (1)
      controlling the expression and recruitment of claudin 2 and recruitment of
      claudin 4 to the TJ, and (2) transient inhibition of the CDC42-JNK pathway. 

PMID- 25588842
TI  - TRPP2-dependent Ca2+ signaling in dorso-lateral mesoderm is required for kidney
      field establishment in Xenopus.
AB  - In Xenopus laevis embryos, kidney field specification is dependent on retinoic
      acid (RA) and coincides with a dramatic increase of Ca(2+) transients, but the
      role of Ca(2+) signaling in the kidney field is unknown. Here, we identify TRPP2,
      a member of the transient receptor potential (TRP) superfamily of channel
      proteins encoded by the pkd2 gene, as a central component of Ca(2+) signaling in
      the kidney field. TRPP2 is strongly expressed at the plasma membrane where it
      might regulate extracellular Ca(2+) entry. Knockdown of pkd2 in the kidney field
      results in the downregulation of pax8, but not of other kidney field genes (lhx1,
      osr1 and osr2). We further show that inhibition of Ca(2+) signaling with an
      inducible Ca(2+) chelator also causes downregulation of pax8, and that pkd2
      knockdown results in a severe inhibition of Ca(2+) transients in kidney field
      explants. Finally, we show that disruption of RA results both in an inhibition of
      intracellular Ca(2+) signaling and of TRPP2 incorporation into the plasma
      membrane of kidney field cells. We propose that TRPP2-dependent Ca(2+) signaling
      is a key component of pax8 regulation in the kidney field downstream of RA
      mediated non-transcriptional control of TRPP2. 

PMID- 25588841
TI  - ESCRT-0 marks an APPL1-independent transit route for EGFR between the cell
      surface and the EEA1-positive early endosome.
AB  - Endosomal sorting complexes required for transport (ESCRT)-0 sorts ubiquitylated
      EGFR within the early endosome so that the receptor can be incorporated into
      intralumenal vesicles. An important question is whether ESCRT-0 acts solely upon
      EGFR that has already entered the vacuolar early endosome (characterised by the
      presence of EEA1) or engages EGFR within earlier compartments. Here, we employ a
      suite of software to determine the localisation of ESCRT-0 at subpixel resolution
      and to perform particle-based colocalisation analysis with other endocytic
      markers. We demonstrate that although some of the ESCRT-0 subunit Hrs (also known
      as HGS) colocalises with the vacuolar early endosome marker EEA1, most localises
      to a population of peripheral EEA1-negative endosomes that act as intermediates
      in transporting EGFR from the cell surface to more central early endosomes. The
      peripheral Hrs-labelled endosomes are distinct from APPL1-containing endosomes,
      but co-label with the novel endocytic adaptor SNX15. In contrast to ESCRT-0,
      ESCRT-I is recruited to EGF-containing endosomes at later times as they move to
      more a central position, whereas ESCRT-III is also recruited more gradually. RNA
      silencing experiments show that both ESCRT-0 and ESCRT-I are important for the
      transit of EGF to EEA1 endosomes.

PMID- 25588845
TI  - Pistagremic acid, a novel beta-secretase enzyme (BACE1) inhibitor from Pistacia
      integerrima Stewart.
AB  - A new triterpenic compound named pistagremic acid (PA) was once again isolated
      from Pistaciaintegerrima. The beta-secretase inhibition study was carried out.
      Compound PA was found significantly active against beta-secretase enzyme (BACE1)
      with IC50 value of 350 +/- 2 nM in comparison to the standard inhibitors [Asn670,
      Sta671, Val672]-amyloid-beta/A4 precursor protein 770 fragment 662-675 (IC50 =
      290.71 +/- 1 nM). The selectivity of this compound was also evaluated against the
      acetylcholinesterase and butyrylcholinesterase enzymes. Interestingly compound PA
      was found to be inactive against them and showed selectivity towards beta
      secretase enzyme (BACE1).

PMID- 25588843
TI  - S1PR1 Tyr143 phosphorylation downregulates endothelial cell surface S1PR1
      expression and responsiveness.
AB  - Activation of sphingosine-1-phosphate receptor 1 (S1PR1) plays a key role in
      repairing endothelial barrier function. We addressed the role of phosphorylation
      of the three intracellular tyrosine residues of S1PR1 in endothelial cells in
      regulating the receptor responsiveness and endothelial barrier function regulated
      by sphingosine 1-phosphate (S1P)-mediated activation of S1PR1. We demonstrated
      that phosphorylation of only Y143 site was required for S1PR1 internalization in
      response to S1P. Maximal S1PR1 internalization was seen in 20 min but S1PR1
      returned to the cell surface within 1 h accompanied by Y143-dephosphorylation.
      Cell surface S1PR1 loss paralleled defective endothelial barrier enhancement
      induced by S1P. Expression of phospho-defective (Y143F) or phospho-mimicking
      (Y143D) mutants, respectively, failed to internalize or showed unusually high
      receptor internalization, consistent with the requirement of Y143 in regulating
      cell surface S1PR1 expression. Phosphorylation of the five S1PR1 C-terminal
      serine residues did not affect the role of Y143 phosphorylation in signaling
      S1PR1 internalization. Thus, rapid reduction of endothelial cell surface
      expression of S1PR1 subsequent to Y143 phosphorylation is a crucial mechanism of
      modulating S1PR1 signaling, and hence the endothelial barrier repair function of
      S1P. 

PMID- 25588844
TI  - Front-signal-dependent accumulation of the RHOA inhibitor FAM65B at leading edges
      polarizes neutrophils.
AB  - A hallmark of neutrophil polarization is the back localization of active RHOA and
      phosphorylated myosin light chain (pMLC, also known as MYL2). However, the
      mechanism for the polarization is not entirely clear. Here, we show that FAM65B,
      a newly identified RHOA inhibitor, is important for the polarization. When FAM65B
      is phosphorylated, it binds to 14-3-3 family proteins and becomes more stable. In
      neutrophils, chemoattractants stimulate FAM65B phosphorylation largely depending
      on the signals from the front of the cells that include those mediated by
      phospholipase Cbeta (PLCbeta) and phosphoinositide 3-kinase gamma (PI3Kgamma),
      leading to FAM65B accumulation at the leading edge. Concordantly, FAM65B
      deficiency in neutrophils resulted in an increase in RHOA activity and
      localization of pMLC to the front of cells, as well as defects in chemotaxis
      directionality and adhesion to endothelial cells under flow. These data together
      elucidate a mechanism for RHOA and pMLC polarization in stimulated neutrophils
      through direct inhibition of RHOA by FAM65B at the leading edge. 

PMID- 25588846
TI  - Giant resonance tuning of micro and nanomechanical oscillators.
AB  - We present a method to tune the resonance frequency and the Q-factor of micro and
      nano-metric mechanical oscillators. A counteracting loop drives a capacitive
      force applied to the oscillator. The proportional and differential gains are used
      to shift the resonance frequency up to 75% and to tune the Q-factor of the
      oscillator, by changing its effective stiffness and damping ratio. The oscillator
      position is monitored in a large bandwidth with a fiber-optic based
      interferometer. We applied this simple operational scheme with different
      oscillators for modifying easily their dynamical properties. Compared to
      alternative methods requiring external fields, our method can either increase or
      decrease the resonance frequency in a frequency range much more extended. This
      opens up a wide range of applications, from force sensors with extremely low
      elastic constants but high quality factor to tunable energy harvesters or to high
      frequency tuning of radio frequency filters. The control scheme can work in
      different media, and is then suitable to be applied to biological sensors and
      actuators. 

PMID- 25588847
TI  - Intramedullary nailing versus proximal plating in the management of closed extra
      articular proximal tibial fracture: a randomized controlled trial.
AB  - BACKGROUND: Extra-articular proximal tibial fractures account for 5-11 % of all
      tibial shaft fractures. In recent years, closed reduction and minimally invasive
      plating and multidirectional locked intramedullary nailing have both become
      widely used treatment modalities for proximal and distal tibial metaphyseal
      fractures. This study was performed to compare plating and nailing options in
      proximal tibia extra-articular fractures. MATERIALS AND METHODS: This randomized
      prospective clinical study was conducted on 58 skeletally mature patients with a
      closed extra-articular fracture of the proximal tibia treated with minimally
      invasive proximal tibial plating (PTP) or intramedullary nailing (IMN) by trained
      surgeons at a tertiary trauma center. RESULTS: Postoperative hospital stay (p =
      0.035), time to full weight-bearing, and union time (p = 0.004) were
      significantly less in the IMN group than in the PTP group, but there was no clear
      advantage of either technique in terms of operative time (p = 0.082), infection
      rate (p = 0.738), range of motion of the knee (p = 0.462), or degrees of malunion
      and nonunion. CONCLUSION: Both implants have shown promising results in extra
      articular proximal tibial fractures, and provide rigid fixation that prevents
      secondary fracture collapse. LEVEL OF EVIDENCE: Level 2, randomized controlled
      trial.

PMID- 25588848
TI  - Coloduodenal fistula due to signet-ring cells adenocarcinoma.

PMID- 25588849
TI  - Other nanoparticles: general discussion.

PMID- 25588851
TI  - Antiasthmatic Effects of Eugenol in a Mouse Model of Allergic Asthma by
      Regulation of Vitamin D3 Upregulated Protein 1/NF-kappaB Pathway.
AB  - The aim of the study was to investigate the antiasthmatic effects of eugenol
      (EUG) and the possible mechanisms. Asthma model was established by ovalbumin
      induction. A total of 50 mice were randomly assigned to five experimental groups:
      control, OVA, OVA + dexamethasone (2 mg/kg), OVA + EUG (10 mg/kg), and OVA + EUG
      (20 mg/kg). Airway resistance (Raw) were measured, histological studies were
      evaluated by the hematoxylin and eosin (HE) staining, interleukin-4 (IL-4) and
      interleukin-5 (IL-5) were evaluated by enzyme-linked immunosorbent assay (ELISA),
      Vitamin D3 upregulated protein 1 (VDUP1), IkappaBalpha, P-IkappaBalpha, NF
      kappaBP65, and p-NF-kappaBP65 were measured by Western blotting. Our study
      demonstrated that EUG inhibited OVA-induced increases in Raw and eosinophil
      count; IL-4 and IL-5 were recovered. Histological studies demonstrated that EUG
      substantially inhibited OVA-induced eosinophilia in the lung tissue. Western
      blotting studies demonstrated that EUG substantially inhibited P-IkappaBalpha, NF
      kappaBP65, and p-NF-kappaBP65 protein levels and increased VDUP1 and IkappaBalpha
      protein levels. These findings suggest that EUG may effectively ameliorate the
      progression of asthma and could be used as a therapy for patients with allergic
      asthma. 

PMID- 25588852
TI  - Biocontrol of Salmonella Enteritidis in spiked chicken cuts by lytic
      bacteriophages PhiSP-1 and PhiSP-3.
AB  - The ability of host specific bacteriophages PhiSP-1 and PhiSP-3 to lyse
      Salmonella in artificially contaminated cuts of pressure cooked chicken meat was
      evaluated at different temperatures -4  degrees C, room temperature (28 +/- 0.5 
      degrees C) and 37  degrees C applying low and high multiplicity of infection
      (MOI). Bacteriophages were able to significantly reduce the bacterial counts at
      all the temperatures studied. At 4  degrees C, individual application of Phi SP-1
      and Phi SP-3 resulted in significant drop in bacterial counts (log10 2.46 and 2.1
      CFU/ml, respectively) at high MOI and (log10 0.98 and 0.52 CFU/ml, respectively)
      at low MOI, when compared to the untreated control on day 3. Similarly at room
      temperature the drop was log10 3.99 and 3.46 CFU/ml at high MOI and log10 2.51
      and 2.3 CFU/ml at low MOI. At 37  degrees C the drop was log10 1.98 and 2.38 at
      high MOI and at low MOI it was log10 1.52 and 1.98 CFU/ml. Increased efficiency
      was observed when phages where applied as cocktail at high MOI as the bacterial
      counts at the end of day 3 dropped by log10 3.52 CFU/ml at 37  degrees C and to
      beyond detectable level at 4  degrees C and room temperature. The average
      reduction of bacterial load in the same group was -4  degrees C (79%), room
      temperature (92%) and 37  degrees C (78%).

PMID- 25588850
TI  - Effect of dipeptidyl peptidase-4 inhibition on circadian blood pressure during
      the development of salt-dependent hypertension in rats.
AB  - A growing body of evidence has indicated that dipeptidyl peptidase-4 (DPP-4)
      inhibitors have antihypertensive effects. Here, we aim to examine the effect of
      vildagliptin, a DPP-4-specific inhibitor, on blood pressure and its circadian
      dipping pattern during the development of salt-dependent hypertension in Dahl
      salt-sensitive (DSS) rats. DSS rats were treated with a high-salt diet (8% NaCl)
      plus vehicle or vildagliptin (3 or 10 mg kg(-1) twice daily by oral gavage) for 7
      days. Blood pressure was measured by the telemetry system. High-salt diet for 7
      days significantly increased the mean arterial pressure (MAP), systolic blood
      pressure (SBP) and were also associated with an extreme dipping pattern of blood
      pressure in DSS rats. Treatment with vildagliptin dose-dependently decreased
      plasma DPP-4 activity, increased plasma glucagon-like peptide 1 (GLP-1) levels
      and attenuated the development of salt-induced hypertension. Furthermore,
      vildagliptin significantly increased urine sodium excretion and normalized the
      dipping pattern of blood pressure. In contrast, intracerebroventricular infusion
      of vildagliptin (50, 500 or 2500 MUg) did not alter MAP and heart rate in DSS
      rats. These data suggest that salt-dependent hypertension initially develops with
      an extreme blood pressure dipping pattern. The DPP-4 inhibitor, vildagliptin, may
      elicit beneficial antihypertensive effects, including the improvement of abnormal
      circadian blood pressure pattern, by enhancing urinary sodium excretion.

PMID- 25588853
TI  - Short-term diabetes- and diuresis-induced alterations of the bladder are mostly
      reversible in rats.
AB  - OBJECTIVES: To determine whether diabetes mellitus- and diuresis-induced
      alterations in the bladder can be reversed in rats. METHODS: Male Sprague-Dawley
      rats were randomly distributed into eight groups (n = 16 per group): 3 weeks and
      11 weeks age-matched controls, 3 weeks and 11 weeks after streptozotocin-induced
      diabetes mellitus, 3 weeks after diabetes mellitus induction then treated with
      insulin for 8 weeks, 3 weeks and 11 weeks after 5% sucrose-induced diuresis, and
      3 weeks after 5% sucrose-induced diuresis followed by removal of 5% sucrose for 8
      weeks. Bodyweight, blood glucose and glycated hemoglobin A1c were monitored. At
      the designated time-points, 24-h urinary habits were examined, and cystometry was
      carried out in half of the animals. The bladders from the remaining animals were
      harvested for histological examination, and quantification of smooth muscle,
      urothelium and collagen components. RESULTS: Insulin treatment reversed
      hyperglycemia and polyuria in diabetic animals successfully, which was shown by
      normalization of blood glucose, glycated hemoglobin A1c and 24-h urinary habits.
      Subsequently, bodyweight, bladder weight and percentage change of bladder
      components (smooth muscle, collagen, urothelium) in total bladder cross-sectional
      area were reversed to almost normal levels, and the bladder dysfunction was
      mostly reversed by 8 weeks of glycemic control, seen in the cystometry study.
      Similar alterations and reversed effects were seen in diuretic rats without and
      with 5% sucrose removal, respectively. CONCLUSIONS: Short-term (3-week induction)
      diabetes- and polyuria-induced functional and morphological alterations of the
      bladder can mostly be reversed in rats.

PMID- 25588854
TI  - Prognostic value of Bcl-2 expression in squamous cell carcinoma of the larynx: a
      systematic review.
AB  - The aim of this systematic review was to determine the prognostic value of Bcl-2
      immunostaining in patients affected by laryngeal squamous cell carcinoma. An
      appropriate search was conducted on PubMed to retrieve articles dealing with this
      topic. A double cross-check was performed on citations and full-text articles by
      2 investigators independently to review all manuscripts and perform a
      comprehensive quality assessment. Of 115 abstracts identified, 15 articles were
      included. These studies reported on 1,150 patients with histologically confirmed
      diagnosis of laryngeal squamous cell carcinoma. Only a few studies showed a
      statistical correlation between Bcl-2 immunohistochemical expression and at least
      1 of the clinical and histopathological parameters considered by the authors.
      Moreover, these findings were also discordant between them. Overall the studies
      analyzed suggested that Bcl-2 expression was statistically connected with N stage
      (2/14), grading (2/14), disease-free survival (3/14) and overall survival (5/14).
      Interestingly, all of the 3 studies investigating the relation between Bcl-2 and
      radioresistance showed significant results in terms of recurrence-free survival
      and overall survival. Our review strongly suggests that the immunohistochemical
      staining of Bcl-2 does not correlate with tumoral aggressiveness and prognosis of
      patients affected by laryngeal squamous cell carcinoma and treated with primary
      surgery. However, an interesting connection of this protein could be demonstrated
      with tumoral radioresistance. Further, high-quality prospective studies should be
      carried out to confirm this hypothesis.

PMID- 25588855
TI  - Clinical significance of subtype classification in metastatic lymph nodes of
      breast cancer patients undergoing neoadjuvant chemotherapy.
AB  - BACKGROUND: Neoadjuvant chemotherapy has been increasingly utilized in the
      treatment of breast cancer patients. However, there are no established surrogate
      markers predicting the response to subsequent adjuvant therapy and clinical
      outcome of patients. In particular, whether primary or lymph nodes metastasis
      should be evaluated for these analyses has remained unknown. Therefore, in this
      study, we first evaluated the differences in biomarkers between primary and
      metastatic cancer tissues in the patients undergoing neoadjuvant chemotherapy. We
      then correlated the findings with the clinical outcomes of these patients.
      METHODS: We examined 49 patients receiving neoadjuvant chemotherapy and
      subsequent surgery with lymph node metastasis. Estrogen receptor (ER),
      progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and
      Ki-67 were all immunohistochemically evaluated in core needle biopsy samples from
      primary and metastatic tumors following chemotherapy. RESULTS: No statistically
      significant differences in these markers were detected between the primary tumor
      and metastatic lymph nodes following therapy, but the Ki-67 labeling index was
      significantly higher in metastatic lymph nodes than in primary tumor (p = 0.017).
      The patients associated with luminal A type carcinoma in their lymph nodes
      following chemotherapy demonstrated significantly better clinical outcomes
      (disease-free survival: p = 0.0045, overall survival: p = 0.0006) than those who
      were not. CONCLUSION: These data indicate that subtype classification following
      chemotherapy, in the metastatic lymph nodes rather than primary tumor could
      predict long-term outcomes of patients undergoing neoadjuvant chemotherapy.

PMID- 25588856
TI  - MGMT promoter methylation and glioblastoma: a comparison of analytical methods
      and of tumor specimens.
AB  - It is already well known that hypermethylation of the O6-methylguanine DNA
      methyltransferase (MGMT) gene promoter is a predictive biomarker of response to
      temozolomide treatment and of favorable outcomes in terms of overall survival
      (OS) and progression-free survival (PFS) in glioblastoma (GBM) patients.
      Nevertheless, MGMT methylation status has not currently been introduced into
      routine clinical practice, as the choice of the ideal technique and tissue sample
      specimen is still controversial. The aim of this study was to compare 2
      analytical methods, methylation-specific polymerase chain reaction (MSP) and
      pyrosequencing (PSQ), and their use on 2 different tissue type samples, snap
      frozen and formalin-fixed paraffin-embedded (FFPE), obtained from a single-center
      and uniformly treated cohort of 46 GBM patients. We obtained methylation data
      from all frozen tissues, while no results were obtained for 5 FFPE samples. The
      highest concordance for methylation was found on frozen tissues (88.5%, 23/26
      samples), using PSQ (76.7%, 23/30 samples). Moreover, we confirmed that OS and
      PFS for patients carrying methylation of the MGMT promoter were longer than for
      patients with an unmethylated promoter. In conclusion, we considered MSP a
      limited technique for FFPE tissues due to the high risk of false-positive
      results; in contrast, our data indicated PSQ as the most powerful method to
      stratify methylated/unmethylated patients as it allows reaching quantitative
      results with high sensitivity and specificity. Furthermore, frozen tumor tissues
      were shown to be the best specimens for MGMT methylation analysis, due to the low
      DNA degradation and homogeneity in methylation throughout the tumor.

PMID- 25588857
TI  - Androgen receptor and enzymes in lymph node metastasis and cancer reoccurrence in
      triple-negative breast cancer.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by the absence
      of estrogen receptor, progesterone receptor and HER2. TNBCs are a diverse
      subgroup, but one promising marker and therapeutic target of this breast cancer
      is the androgen receptor (AR). Previously we demonstrated that AR and cognate
      intracrine pathways are associated with decreased proliferation in invasive
      ductal carcinoma with their decrease also detected between organ-confined and
      invasive diseases. Therefore, in this study, we examined the status of AR and
      androgen-producing enzymes during the process of metastasis to lymph nodes and
      cancer recurrence. MATERIALS AND METHODS: We studied 2 series of patients with
      TNBC, one from Kumamoto University Hospital composed of 16 matched cases of
      primary and locally or distal recurrences and the other from Tohoku University
      Hospital examining 46 lymph node metastasis from 23 patients. In addition to
      studying concordance in AR expression, we also examined the interactions between
      AR and Ki-67 labeling index and AR and site of distal metastasis. RESULTS: In
      both series, AR status was concordant between primary and recurrent/metastatic
      disease, but coordinated expression of AR and androgenic enzymes was lost during
      the process. The inverse association between AR and Ki-67, previously reported in
      invasive ductal carcinoma (IDC), was markedly potentiated in both lymph node and
      recurrent cancers. In addition, AR expression appeared to have little effect on
      visceral metastasis but was associated directly with bone metastasis and
      inversely with brain metastasis. CONCLUSIONS: The results of our present study
      demonstrated that AR remained in the majority of metastatic samples from AR
      positive primary TNBCs and that AR manipulation could be exploited in the
      metastatic settings of TNBC.

PMID- 25588858
TI  - The relation between CA 19-9 level and early-phase insulin secretion in
      normoglycemic and prediabetic subjects.
AB  - BACKGROUND: Carbohydrate antigen (CA) 19-9 is used as a clinical tumor marker of
      pancreatic cancer; recent studies report that CA 19-9 is also associated with
      changes in blood glucose levels. The aim of the present study was to investigate
      the relationship between serum CA 19-9 levels and early-phase insulin secretion
      in nondiabetic individuals. METHODS: We enrolled 269 normoglycemic participants
      and 172 prediabetic participants who had undergone the 75-g oral glucose
      tolerance test during their annual health examination. Insulin secretion was
      estimated using the disposition index (DI) [(Deltainsulin(0-30
      min)/Deltaglucose(0-30 min) * (1/HOMA-IR)], which is an adjusted measure of
      relationship between beta-cell sensitivity and insulin sensitivity. RESULTS:
      Serum CA 19-9 level was significantly higher in the prediabetic participants than
      in the normoglycemic participants. Simple linear regression analysis showed a
      negative correlation between CA 19-9 levels and DI for all participants and
      prediabetic participants (r = -0.126, p = 0.009, and r = -0.189, p = 0.002,
      respectively). However, in the normoglycemic participants, CA 19-9 levels did not
      correlate with DI. For all participants, and prediabetic subjects, multivariate
      linear regression analysis revealed that serum CA 19-9 levels were one of the
      independent predictors of DI (adjusted beta = -0.098, p = 0.025, and adjusted
      beta = -0.177, p = 0.004, respectively). CONCLUSIONS: Serum CA 19-9 levels
      significantly correlate with early-phase insulin secretion in the prediabetic
      individuals. Our results indicate that CA 19-9 may be involved in the endocrine
      function of pancreas.

PMID- 25588859
TI  - Lung adenocarcinoma with concurrent KRAS mutation and ALK rearrangement
      responding to crizotinib: case report.
AB  - Chromosomal translocation resulting in the fusion between the echinoderm
      microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma
      kinase (ALK) gene was recently identified as a novel genetic alteration in a
      subset of non-small cell lung cancer (NSCLC). EML4-ALK translocations are rare
      events associated with specific clinicopathological features, such as never or
      light smoking history, young age and adenocarcinoma with signet ring or acinar
      histology. Reports suggest ALK gene arrangements are mutually exclusive with EGFR
      and KRAS mutations. To the best of to our knowledge, this is the first case
      report of a patient with concurrent KRAS mutation and ALK translocation. This
      patient had an excellent response to crizotinib, suggesting that the ALK
      translocation was the oncogenic driver.

PMID- 25588860
TI  - Measurement of a urinary marker (8-hydroxydeoxy-guanosine, 8-OHdG) of DNA
      oxidative stress in epidemiological surveys: a pilot study.
AB  - BACKGROUND: 8-Hydroxydeoxyguanosine (8-OHdG) is a commonly used marker of DNA
      oxidative stress in epidemiological studies. The aim of this study was to
      establish whether the urinary concentration of 8-OHdG varies during the first
      part of the day, when clinical tests are usually performed, and whether it can
      therefore be measured without bias in spot urine samples. MATERIAL AND METHODS:
      Spot urine samples were collected using a convenience sample. A linear mixed
      effects model for repeated measurements was used to analyze 8-OHdG levels.
      RESULTS: A significant increasing trend in time in the 8-OHdG concentration was
      found among smokers, but not in the case of nonsmokers. CONCLUSIONS: In
      epidemiological studies on oxidative stress, all participants should collect
      their early morning urine specimens - before their first cigarette if they are
      smokers - to gather information on individual background oxidation levels.

PMID- 25588861
TI  - Change of hemopexin level is associated with the severity of sepsis in
      endotoxemic rat model and the outcome of septic patients.
AB  - PURPOSE: The purpose of the study is to uncover the role of hemopexin (HPX) as
      anti-inflammatory mediator in animals and humans. MATERIALS AND METHODS: We
      injected rats with 5 and 10 mg/kg of lipopolysaccharide to induce low- and high
      grade endotoxemia (LGE and HGE), respectively, and we measured serum levels of
      tumor necrosis factor alpha, interleukin 6, and HPX at 0, 1, 3, and 6 hours after
      the injection. In a clinical study, we measured the initial serum HPX
      concentrations of septic shock patients. We evaluated the correlation between HPX
      levels and sepsis severity in rats and the predictive value of the HPX level for
      28-day mortality of patients. RESULTS: In rats, serum interleukin 6 and tumor
      necrosis factor alpha concentrations were lower in LGE than in HGE, whereas the
      HPX level in HGE at 6 hours was significantly lower than in LGE (0.88,
      interquartile range [0.79-1.00] vs 1.33, interquartile range [1.29-1.49] mg/mL,
      P= .002). In patients, the initial serum HPX level in nonsurvivors was
      significantly lower than in survivors (0.75 vs 1.02 mg/mL, P< .001). Multivariate
      logistic regression analysis revealed that HPX exhibited independent prognostic
      value for 28-day mortality, and its levels were closely related to Acute
      Physiology and Chronic Health Evaluation II scores. CONCLUSIONS: Low serum HPX
      levels are related to sepsis severity and could indicate poor prognosis for
      septic shock patients.

PMID- 25588862
TI  - Chronic liver disease and 90-day mortality in 21,359 patients following peptic
      ulcer bleeding--a Nationwide Cohort Study.
AB  - BACKGROUND: Bleeding is a serious and frequent complication of peptic ulcer
      disease. Hepatic dysfunction can cause coagulopathy and increases the risk of
      peptic ulcer bleeding. However, whether chronic liver disease increases mortality
      after peptic ulcer bleeding remains unclear. AIM: To examine the prognostic
      impact of chronic liver disease on mortality after peptic ulcer bleeding.
      METHODS: We used population-based medical registries to conduct a cohort study of
      all Danish residents hospitalised with incident peptic ulcer bleeding from 2004
      through 2011. We identified patients diagnosed with liver cirrhosis or non
      cirrhotic chronic liver disease before their admission for peptic ulcer bleeding.
      We then computed 90-day mortality after peptic ulcer bleeding based on the Kaplan
      Meier method (1 - survival function) and used a Cox regression model to estimate
      mortality rate ratios (MRRs), controlling for potential confounders. RESULTS: We
      identified 21,359 patients hospitalised with peptic ulcer bleeding. Among these,
      653 (3.1%) had a previous diagnosis of liver cirrhosis and 474 (2.2%) had a
      history of non-cirrhotic chronic liver disease. Patients with liver cirrhosis and
      non-cirrhotic chronic liver disease had a cumulative 90-day mortality of 25.3%
      and 20.7%, respectively, compared to 18.3% among patients without chronic liver
      disease. Liver cirrhosis was associated with an adjusted 90-day MRR of 2.38 (95%
      CI: 2.02-2.80), compared to 1.49 (95% CI: 1.22-1.83) among patients with non
      cirrhotic chronic liver disease. CONCLUSION: Patients with chronic liver disease,
      particularly liver cirrhosis, are at increased risk of death within 90 days after
      hospitalisation for peptic ulcer bleeding compared to patients without chronic
      liver disease.

PMID- 25588863
TI  - Confinement of massless Dirac fermions in the graphene matrix induced by the B/N
      heteroatoms.
AB  - In this work, the systems are constructed with the defect lines of B-B or N-N
      dimers embedded in a graphene matrix using density functional theory. It is found
      that the Dirac-cone dispersions appear at the Fermi level in the bands introduced
      by the B or N heteroatom, linear B-B or N-N dimers, demonstrating that the
      carrier mobility is ~10(6) m s(-1) which is comparable with that of the pristine
      graphene. Most importantly, such dimer lines act as the quasi-1-D conducting
      nanowires whose charge carriers are confined around the linear defects in these
      dimers while the charge carriers in pristine graphene are dispersed two
      dimensionally. Such systems suggest that heteroatoms in graphene can indeed
      contribute to the Dirac cone. In addition, the type of carriers (p-type or n
      type) can be manipulated using the B or N heteroatoms, respectively. This will
      greatly enrich the electronic properties of Dirac semimetals. 

PMID- 25588864
TI  - Autophagy inhibition by caffeine increases toxicity of methamphetamine in SH-SY5Y
      neuroblastoma cell line.
AB  - Methamphetamine (METH) is a highly addictive CNS stimulant that its long-term use
      is associated with the loss of neurons in substantia nigra and development of
      Parkinson's disease later in life. Common form of METH is Ya-Ba tablet, in which,
      large portion of caffeine is added to the mass to enhance the stimulatory effect.
      Previous study demonstrated that caffeine potentiates the toxic effect of METH in
      association with the production of reactive oxygen species and the induction of
      apoptosis. Since METH causes induction of autophagy, the question was raised
      whether this pathway participates in the potentiating effect of caffeine on METH
      neurotoxicity. We used SH-SY5Y, a neuroblastoma cell line, as an in vitro model
      to study the effect of METH and caffeine. Co-treatment of non-toxic
      concentrations of METH, at 0.5 mM, and caffeine, at 1 mM, caused reduction of the
      cell viability. Reduction of the cell viability was associated with attenuation
      of autophagy, demonstrated by reduction of LC3-II levels and the number of
      autophagosome puncta, together with increase of caspase-3 activation. Similar
      effect was produced by treatment with autophagy inhibitors, 3-MA and wortmanin.
      Our results suggested that caffeine potentiates METH toxicity through inhibition
      of autophagy and that autophagy serves as a protective mechanism. In conclusion,
      we proposed the augmented hazard associated with caffeine and METH combination in
      Ya-Ba abusers.

PMID- 25588865
TI  - Toxic effects of bortezomib on primary sensory neurons and Schwann cells of adult
      mice.
AB  - The proteasome inhibitor bortezomib is nowadays first line treatment for multiple
      myeloma. One of the most significant adverse events is peripheral neuropathy,
      mainly involving sensory nerve fibers that can lead to withdrawal of treatment.
      Here we develop an in vitro model to compare the effects of bortezomib on primary
      sensory neurons and Schwann cells of adult mice. We observed that sensory neurons
      were more susceptible to bortezomib, and their viability was reduced at a
      concentration of 6 nM, that only affected Schwann cell proliferation but not
      survival. At concentration higher than 8 nM Schwann cell viability was also
      compromised. Already at low concentrations, surviving neurons presented
      alterations in neurite outgrowth. Neurites were shorter and had dystrophic
      appearance, with alterations in neurofilament staining. However, neurites were
      able to regrow after removing bortezomib from the medium, thus indicating
      reversibility of the neurotoxicity. We confirmed in vivo that bortezomib produced
      alterations in neurofilaments at early stages of the treatment. After an
      accumulated dose of 2 mg/kg bortezomib, dorsal root ganglia neurons of treated
      animals showed accumulation of neurofilament in the soma. To evaluate if this
      accumulation was related with alterations in axonal transport, we tested the
      ability of sensory neurons to retrogradely transport a retrotracer applied at the
      distal nerve. Treated animals showed a lower amount of retrotracer in the soma 24
      h after its application to the tibial nerve, therefore suggesting that axonal
      transport was affected by bortezomib.

PMID- 25588866
TI  - Mesenchymal stem cells inhibit Th17 cells differentiation via IFN-gamma-mediated
      SOCS3 activation.
AB  - Mesenchymal stem cells (MSCs) are immunoregulatory, and the administration of
      them has been shown to ameliorate inflammation caused by Th17 cells. However, the
      mechanisms that contribute to MSC regulation on Th17 cell development are
      unclear. Here, we found that MSCs could inhibit Th17 cell differentiation through
      the activation of suppressors of cytokine signaling 3 (SOCS3) when coculture of
      MSCs and CD4(+)CD25(low)CD44(low)CD62L(high) T cells. Further analysis
      demonstrated that the inhibitory action was mediated via interferon gamma (IFN
      gamma), which activated signal transducer and activator of transcription-1
      (STAT1) to enhance the expression of SOCS3, leading to STAT3 inhibition.
      Moreover, stable and reciprocal changes in H3K4me3 and H3K27me3 at the promoters
      of STAT1, STAT3 and RORgammat determined the fate of Th17 cells. These results
      demonstrate that MSCs may inhibit Th17 differentiation via IFN-gamma that
      activates SOCS3 leading to immunomodulatory effects, suggesting a possible
      mechanism by which MSCs could act as a cellular approach to attenuate the
      clinical and pathological manifestations of some autoimmune diseases. 

PMID- 25588867
TI  - c-kit plays a critical role in induction of intravenous tolerance in experimental
      autoimmune encephalomyelitis.
AB  - c-kit (CD117) is a tyrosine kinase receptor found in various types of immune
      cells. It has been shown that c-kit plays a role in the pathogenesis of multiple
      sclerosis, an inflammatory demyelinating disorder of the CNS. Recent data have
      suggested an immunoregulatory effect of c-kit. We therefore examined the role of
      c-kit in autoantigen-induced i.v. tolerance in experimental autoimmune
      encephalomyelitis (EAE), an animal model of MS. Our results show that induction
      of intravenous tolerance against EAE in B6 mice is characterized by increased
      numbers of CD117(+) cells and altered mast cell-associated molecules in the
      periphery and in the CNS. W(-sh) (c-kit-deficient) mice were resistant to i.v
      autoantigen-induced tolerance, with increased proinflammatory cytokine production
      in the periphery. I.v. autoantigen in WT mice suppressed the production of
      proinflammatory cytokines IFN-gamma and IL-6 and up-regulated the expression of
      FoxP3, a transcription factor of Tregs; however, in W(-sh) mice, IFN-gamma and IL
      6 were increased with a failure of FoxP3 induction upon i.v. autoantigen
      injection and is thus a mechanism for resistance to i.v. tolerance induction in
      these mice. We conclude that c-kit signaling has a regulatory role in i.v.
      tolerance and could be a target for potential immunotherapy in autoimmune
      disorders. 

PMID- 25588871
TI  - Ethical issues in isolating people treated for Ebola.

PMID- 25588870
TI  - Evidence for shared deficits in identifying emotions from faces and from voices
      in autism spectrum disorders and specific language impairment.
AB  - BACKGROUND: While autism spectrum disorder (ASD) and specific language impairment
      (SLI) have traditionally been conceptualized as distinct disorders, recent
      findings indicate that the boundaries between these two conditions are not clear
      cut. While considerable research has investigated overlap in the linguistic
      characteristics of ASD and SLI, relatively less research has explored possible
      overlap in the socio-cognitive domain, particularly in terms of the emotion
      recognition abilities of these two groups of children. AIMS: To investigate
      facial and vocal emotion recognition in children with ASD, children with SLI and
      typically developing (TD) children. To do so, the ASD group was subdivided into
      those with 'normal' (ALN) and those with 'impaired' (ALI) language to explore the
      extent to which language ability influenced performance on the emotion
      recognition task. METHODS & PROCEDURES: Twenty-nine children with ASD (17 ALN and
      12 ALI), 18 children with SLI and 66 TD children completed visual and auditory
      versions of an emotion recognition task. For the visual version of the task, the
      participants saw photographs of people expressing one of six emotions (happy,
      sad, scared, angry, surprised, disgusted) on the whole face. For the auditory
      modality, the participants heard a neutral sentence that conveyed one of the six
      emotional expressions in the tone of the voice. In both conditions, the children
      were required to indicate how the person they could see/hear was feeling by
      selecting a cartoon face that was presented on the computer screen. OUTCOMES &
      RESULTS: The results showed that all clinical groups were less accurate than the
      TD children when identifying emotions on the face and in the voice. While the ALN
      children were less accurate than the TD children only when identifying
      expressions that require inferring another's mental state (surprise, disgust)
      emotional expressions, the ALI and the SLI children were less accurate than the
      TD children when identifying the basic (happy, sad, scared, angry) as well as the
      inferred emotions. CONCLUSIONS & IMPLICATIONS: The results indicate that children
      with ALI and children with SLI share emotion recognition deficits, which are
      likely to be driven by the poor language abilities of these two groups.

PMID- 25588868
TI  - SEW2871 protects from experimental colitis through reduced epithelial cell
      apoptosis and improved barrier function in interleukin-10 gene-deficient mice.
AB  - Loss of intestinal epithelial barrier function including typical tight junction
      changes and epithelial cell apoptosis plays an important role in Crohn's disease.
      SEW2871, a selective sphingosine-1-phosphate type-1 receptor agonist, has been
      proven to be efficient in protecting against colitis in IL-10(-/-) mice in our
      previous study. Here we performed additional studies to investigate whether
      treatment with SEW2871 was associated with an improved epithelial barrier
      function in IL-10(-/-) mice. SEW2871 was administered by gavage at a dose of 20
      mg/kg/day for 2 weeks to IL-10(-/-) mice. Severity of colitis, CD4+ T cells in
      colon lamina propria and proinflammatory cytokine productions were evaluated.
      Furthermore, intestinal permeability, tight junction (occludin and ZO-1)
      expressions and distributions, as well as epithelial cell apoptosis, were also
      assessed. SEW2871 treatment attenuated established colitis associated with
      decreased CD4+ T cells in colon lamina propria and reduced TNF-alpha and IFN
      gamma levels. Moreover, enhanced barrier function, which resulted from
      ameliorated tight junction (occludin and ZO-1) expressions and suppressed
      epithelial cell apoptosis, was found to contribute to the therapeutic effects.
      SEW2871 treatment protects from colitis in IL-10(-/-) mice through reduced
      epithelial cell apoptosis and improved barrier function. Thus, targeting
      sphingosine-1-phosphate may represent a new therapeutic approach in Crohn's
      disease.

PMID- 25588872
TI  - Many older people may be overtreated for diabetes, US study finds.

PMID- 25588873
TI  - Model for a patient-centered comparative effectiveness research center.
AB  - This special report describes the systematic approach the University of
      Pittsburgh and the University of Pittsburgh Medical Center (UPMC) undertook in
      creating an infrastructure for comparative effectiveness and patient-centered
      outcomes research resources. We specifically highlight the administrative
      structure, communication and training opportunities, stakeholder engagement
      resources, and support services offered.

PMID- 25588874
TI  - Inhibitory role of REV-ERBalpha in the expression of bone morphogenetic protein
      gene family in rat uterus endometrium stromal cells.
AB  - Uterus circadian rhythms have been implicated in the gestation processes of
      mammals through entraining of the clock proteins to numerous downstream genes.
      Bone morphogenetic proteins (BMPs), having clock-controlled regulatory sites in
      their gene promoters, are expressed in the uterus during decidualization, but the
      regulation of the Bmp gene expression is poorly understood. The present study was
      designed to dissect the physiological roles of the uterus oscillators in the Bmp
      expression using the uterus endometrial stromal cells (UESCs) isolated from Per2
      dLuc transgenic rats on day 4.5 of gestation. The in vitro decidualization of
      UESCs was induced by medroxyprogesterone acetate and 2-O-dibutyryl cAMP. A
      significant decline of Per2-dLuc bioluminescence activity was induced in decidual
      cells, and concomitantly, the expression of canonical clock genes was
      downregulated. Conversely, the expression of the core Bmp genes Bmp2, Bmp4, Bmp6,
      and Bmp7 was upregulated. In UESCs transfected with Bmal1-specific siRNA, in
      which Rev-erbalpha expression was downregulated, Bmp genes, such as Bmp2, Bmp4,
      and Bmp6 were upregulated. However, Bmp1, Bmp7, and Bmp8a were not significantly
      affected by Bmal1 silencing. The expression of all Bmp genes was enhanced after
      treatment with the REV-ERBalpha antagonist (SR8278), although their rhythmic
      profiles were differed from each other. The binding of REV-ERBalpha to the
      proximal regions of the Bmp2 and Bmp4 promoters was revealed by chromatin
      immunoprecipitation-PCR analysis. Collectively, these results indicate that the
      Bmp genes are upregulated by the attenuation of the cellular circadian clock; in
      particular, its core component REV-ERBalpha functions as a transcriptional
      silencer in the Bmp gene family.

PMID- 25588876
TI  - Functional analysis of matriptase-2 mutations and domains: insights into the
      molecular basis of iron-refractory iron deficiency anemia.
AB  - Mutations in the TMPRSS6 gene are associated with severe iron-refractory iron
      deficiency anemia resulting from an overexpression of hepcidin, the key regulator
      of iron homeostasis. The matriptase (MT)-2 protein (encoded by the TMPRSS6 gene)
      regulates hepcidin expression by cleaving hemojuvelin [HJV/hemochromatosis type 2
      (HFE2)], a bone morphogenetic protein (BMP) coreceptor in the hepcidin regulatory
      pathway. We investigated the functional consequences of five clinically
      associated TMPRSS6 variants and the role of MT-2 protein domains by generating
      epitope-tagged mutant and domain-swapped MT-2-MT-1 (encoded by the ST14 gene)
      chimeric constructs and expressing them in HepG2/C3A cells. We developed a novel
      cell culture immunofluorescence assay to assess the effect of MT-2 on cell
      surface HJV expression levels, compatible with HJV cleavage. The TMPRSS6 variants
      Y141C, I212T, G442R, and C510S were retained intracellularly and were unable to
      inhibit BMP6 induction of hepcidin. The R271Q variant, although it has been
      associated with iron-refractory iron deficiency anemia, appears to remain
      functional. Analysis of the chimeric constructs showed that replacement of sperm
      protein, enterokinase, and agrin (SEA), low-density-lipoprotein receptor class A
      (LDLRA), and protease (PROT) domains from MT-2 with those from MT-1 resulted in
      limited cell surface localization, while the complement C1r/C1s, Uegf, Bmp1 (CUB)
      domain chimera retained localization at the cell surface. The SEA domain chimera
      was able to reduce cell surface HJV expression, while the CUB, LDLRA, and PROT
      domain chimeras were not. These studies suggest that the SEA and LDLRA domains of
      MT-2 are important for trafficking to the cell surface and that the CUB, LDLRA,
      and PROT domains are required for cleavage of HJV.

PMID- 25588877
TI  - Lipolytic inhibitor G0/G1 switch gene 2 inhibits reactive oxygen species
      production and apoptosis in endothelial cells.
AB  - G0/G1 switch gene 2 (G0S2), a novel target gene of peroxisome proliferator
      activated receptor, is highly expressed in fat tissues. G0S2 acts as proapoptotic
      factor toward human cancer cells. Endothelial cell (EC) apoptosis may be an
      initiating event in the development of atherosclerosis. However, the expression
      and function of G0S2 in vascular ECs remain unknown. Here, we reported for the
      first time that G0S2 is expressed in arterial ECs. Ectopic expression of G0S2
      increased neutral lipid accumulation in cultured ECs. However, G0S2 prevented ECs
      from serum-free starvation stress- and hydrogen peroxide (H2O2)-induced
      apoptosis. G0S2 blocked the H2O2-induced dissipation of mitochondrial membrane
      potential. G0S2 decreased the release of cytochrome c from mitochondria into the
      cytosol, followed by activation of caspase-9 and caspase-3. The anti-apoptotic
      effect of G0S2 was Bcl-2 and adipose triglyceride lipase independent. In
      contrast, gene silence of G0S2 increased serum-free starvation stress-induced EC
      apoptosis and decreased the formation of capillary-like structures. We further
      found that G0S2 couples with the F0F1-ATP synthase in ECs. Levels of ATP were
      elevated, whereas reactive oxygen species levels were reduced in G0S2-expressing
      ECs. G0S2 can inhibit endothelial denudation secondary to H2O2-induced injury to
      ECs in vivo. These results indicate that G0S2 acts as a prosurvival molecule in
      ECs. Taken together, our results indicate that G0S2 has a protective function in
      ECs and may be a potential target for the treatment of cardiovascular diseases
      associated with reactive oxygen species-induced EC injury, such as
      atherosclerosis and restenosis. 

PMID- 25588875
TI  - P2X7 receptor inhibition protects against ischemic acute kidney injury in mice.
AB  - Activation of the purinergic P2X7 receptor (P2X7R) has been associated with the
      development of experimental nephritis and diabetic and hypertensive nephropathy.
      However, its role in acute kidney injury (AKI) remains unknown. In this study, we
      examined the effects of P2X7R inhibition in a murine model of ischemia
      reperfusion (I/R)-induced AKI using A438079, a selective inhibitor of P2X7R. At
      24 h after I/R, mice developed renal dysfunction and renal tubular damage, which
      was accompanied by elevated expression of P2X7R. Early administration of A438079
      immediately or 6 h after the onset of reperfusion protected against renal
      dysfunction and attenuated kidney damage whereas delayed administration of
      A438079 at 24 h after restoration of perfusion had no protective effects. The
      protective actions of A438079 were associated with inhibition of renal tubule
      injury and cell death and suppression of renal expression of monocyte chemotactic
      protein-1 and regulated upon expression normal T cell expressed and secreted
      (RANTES). Moreover, I/R injury led to an increase in phosphorylation (activation)
      of extracellular signal-regulated kinases 1/2 in the kidney; treatment with
      A438079 diminished this response. Collectively, these results indicate that early
      P2X7R inhibition is effective against renal tubule injury and proinflammatory
      response after I/R injury and suggest that targeting P2X7R may be a promising
      therapeutic strategy for treatment of AKI. 

PMID- 25588878
TI  - Increasing the number of patients receiving information about transition to end
      of-life care: the effect of a half-day physician and nurse training.
AB  - INTRODUCTION: Honest prognostication and information for patients are important
      parts of end-of-life care. This study examined whether an educational
      intervention could increase the proportion of patients who received information
      about the transition to end-of-life (ITEOL care). METHOD: Two municipalities (in
      charge of nursing homes) and two hospitals were randomised to receive an
      interactive half-day course about ITEOL for physicians and nurses. The proportion
      of patients who received ITEOL was measured with data from the Swedish Register
      of Palliative Care (SRPC). Patients were only included if they died an expected
      death and maintained their ability to express their will until days or hours
      before their death. Four hospitals and four municipalities were assigned
      controls, matched by hospital size, population and proportion of patients
      receiving ITEOL at baseline. RESULTS: The proportion of patients in the
      intervention group who received ITEOL increased from 35.1% (during a 6-month
      period before the intervention) to 42% (during a 6-month period after the
      intervention). The proportion in the control group increased from 30.4% to 33.7%.
      The effect of the intervention was significant (p=0.005) in a multivariable model
      adjusted for time, age, gender and cause of death. CONCLUSION: More patients at
      end-of-life received ITEOL after an educative half-day intervention directed to
      physicians and nurses.

PMID- 25588879
TI  - Reversible catalytic dehydrogenation of alcohols for energy storage.
AB  - Reversibility of a dehydrogenation/hydrogenation catalytic reaction has been an
      elusive target for homogeneous catalysis. In this report, reversible acceptorless
      dehydrogenation of secondary alcohols and diols on iron pincer complexes and
      reversible oxidative dehydrogenation of primary alcohols/reduction of aldehydes
      with separate transfer of protons and electrons on iridium complexes are shown.
      This reactivity suggests a strategy for the development of reversible fuel cell
      electrocatalysts for partial oxidation (dehydrogenation) of hydroxyl-containing
      fuels. 

PMID- 25588880
TI  - Correction for Lewis et al., Angelman syndrome imprinting center encodes a
      transcriptional promoter.

PMID- 25588881
TI  - Hierarchical assembly of a dual-responsive macroscopic insulated molecular wire
      bundle in a gradient system.
AB  - Here, we report the hierarchical self-assembly of a cationic gemini amphiphile,
      Azo 1, in a composition gradient solution generated using solvent evaporation. As
      the gradient solution is formed, Azo 1 forms nanorods in the lower region of the
      solution. Depending on solvent composition, these nanorods can further develop
      into nanofibres, which can then intertwine to form double helices and other types
      of nanohelices in the upper region of the solution. Finally, a macroscopic wire
      bundle is formed via the fusion of nanohelices; this ribbon-like bundle exhibits
      elasticity and linear ohmic resistance properties. More intriguingly, this bundle
      exhibits photoresponsive properties that affect its deformation and conductivity,
      as well as a rapid electroresponse that affects its conductivity, indicating that
      it is feasible to control the charge pathway. 

PMID- 25588882
TI  - Factor structure and temporal stability of the Vancouver Obsessional Compulsive
      Inventory-Mental Contamination Scale (VOCI-MC) and psychometric properties of its
      Italian version.
AB  - OBJECTIVE: The Vancouver Obsessional Compulsive Inventory-Mental Contamination
      Scale (VOCI-MC) is a self-report instrument that assesses symptoms of mental
      contamination. The aim of this study was to investigate the psychometric
      properties of the Italian version of the VOCI-MC in non-clinical and clinical
      samples. METHOD: Factor structure, internal consistency, temporal stability,
      construct and criterion validity were investigated in 541 participants from the
      general population, 120 participants diagnosed with OCD and 31 participants
      diagnosed with other anxiety disorders (OAD). For some of these analyses, our OCD
      sample was subdivided into those with contamination-related symptoms and concerns
      (n=39) and those whose OCD excluded concerns related to contamination fear
      (n=81). Exploratory and confirmatory factor analyses supported the expected one
      factor structure of the VOCI-MC both in non-clinical and OCD sample. RESULTS:
      VOCI-MC scores showed good internal consistency, temporal stability, construct
      validity and criterion validity. In particular, the VOCI-MC successfully
      discriminated between those with OCD who reported contamination-related concerns
      and all other groups of participants. CONCLUSION: These findings suggest that the
      Italian version of the VOCI-MC retains the adequate psychometric properties of
      the original, provide preliminary evidence of its one-factor structure and
      temporal stability, and suggest that it can be confidently used as an assessment
      tool of mental contamination symptoms in both clinical and research settings.

PMID- 25588883
TI  - Seaweed cultivation: potential and challenges of crop domestication at an
      unprecedented pace.

PMID- 25588884
TI  - Temperament and Parenting Styles in Early Childhood Differentially Influence
      Neural Response to Peer Evaluation in Adolescence.
AB  - Behavioral inhibition (BI) is a temperament characterized by social reticence and
      withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety
      disorder. Developmental outcomes associated with this temperament can be
      influenced by children's caregiving context. The convergence of a child's
      temperamental disposition and rearing environment is ultimately expressed at both
      the behavioral and neural levels in emotional and cognitive response patterns to
      social challenges. The present study used functional neuroimaging to assess the
      moderating effects of different parenting styles on neural response to peer
      rejection in two groups of adolescents characterized by their early childhood
      temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21
      without BI). The moderating effects of authoritarian and authoritative parenting
      styles were examined in three brain regions linked with social anxiety:
      ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth
      characterized with BI in childhood, but not in those without BI, diminished
      responses to peer rejection in vlPFC were associated with higher levels of
      authoritarian parenting. In contrast, all youth showed decreased caudate response
      to peer rejection at higher levels of authoritative parenting. These findings
      indicate that BI in early life relates to greater neurobiological sensitivity to
      variance in parenting styles, particularly harsh parenting, in late adolescence.
      These results are discussed in relation to biopsychosocial models of development.

PMID- 25588886
TI  - Bringing down the host: enteropathogenic and enterohaemorrhagic Escherichia coli
      effector-mediated subversion of host innate immune pathways.
AB  - Enteric bacterial pathogens commonly use a type III secretion system (T3SS) to
      successfully infect intestinal epithelial cells and survive and proliferate in
      the host. Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC; EHEC)
      colonize the human intestinal mucosa, form characteristic histological lesions on
      the infected epithelium and require the T3SS for full virulence. T3SS effectors
      injected into host cells subvert cellular pathways to execute a variety of
      functions within infected host cells. The EPEC and EHEC effectors that subvert
      innate immune pathways--specifically those involved in phagocytosis, host cell
      survival, apoptotic cell death and inflammatory signalling--are all required to
      cause disease. These processes are reviewed within, with a focus on recent work
      that has provided insights into the functions and host cell targets of these
      effectors.

PMID- 25588885
TI  - Thromboresistant/anti-biofilm catheters via electrochemically modulated nitric
      oxide release.
AB  - Inexpensive nitric oxide (NO) release strategies to prevent thrombosis and
      bacterial infections are desirable for implantable medical devices. Herein, we
      demonstrate the utility of electrochemically modulated NO release from a catheter
      model using an inner copper wire working electrode and an inorganic nitrite salt
      solution reservoir. These catheters generate NO surface fluxes of >1.0 * 10(
      10)mol min(-1) cm(-2) for more than 60 h. Catheters with an NO flux of 1.1 * 10(
      10)mol min(-1) cm(-2) are shown to significantly reduce surface thrombus
      formation when implanted in rabbit veins for 7h. Further, the ability of these
      catheters to exhibit anti-biofilm properties against bacterial species commonly
      causing bloodstream and urinary catheter infections is examined. Catheters
      releasing NO continuously during the 2d growth of Staphylococcus aureus exhibit a
      6 log-unit reduction in viable surface bacteria. We also demonstrate that
      catheters generating NO for only 3h at a flux of 1.0 * 10(-10)mol min(-1) cm(-2)
      lower the live bacterial counts of both 2d and 4d pre-formed Escherichia coli
      biofilms by >99.9%. Overall, the new electrochemical NO-release devices could
      provide a cost-effective strategy to greatly enhance the biocompatibility and
      antimicrobial properties of intravascular and urinary catheters, as well as other
      implantable medical devices.

PMID- 25588887
TI  - Transforming health professions' education through in-country collaboration:
      examining the consortia among African medical schools catalyzed by the Medical
      Education Partnership Initiative.
AB  - BACKGROUND: African medical schools have historically turned to northern partners
      for technical assistance and resources to strengthen their education and research
      programmes. In 2010, this paradigm shifted when the United States Government
      brought forward unprecedented resources to support African medical schools. The
      grant, entitled the Medical Education Partnership Initiative (MEPI) triggered a
      number of south-south collaborations between medical schools in Africa. This
      paper examines the goals of these partnerships and their impact on medical
      education and health workforce planning. METHODS: Semi-structured interviews were
      conducted with the Principal Investigators of the first four MEPI programmes that
      formed an in-country consortium. These interviews were recorded, transcribed and
      coded to identify common themes. RESULTS: All of the consortia have prioritized
      efforts to increase the quality of medical education, support new schools in
      country and strengthen relations with government. These in-country partnerships
      have enabled schools to pool and mobilize limited resources creatively and
      generate locally-relevant curricula based on best-practices. The established
      schools are helping new schools by training faculty and using grant funds to
      purchase learning materials for their students. The consortia have strengthened
      the dialogue between academia and policy-makers enabling evidence-based health
      workforce planning. All of the partnerships are expected to last well beyond the
      MEPI grant as a result of local ownership and institutionalization of
      collaborative activities. CONCLUSIONS: The consortia described in this paper
      demonstrate a paradigm shift in the relationship between medical schools in four
      African countries. While schools in Africa have historically worked in silos,
      competing for limited resources, MEPI funding that was leveraged to form in
      country partnerships has created a culture of collaboration, overriding the
      history of competition. The positive impact on the quality and efficiency of
      health workforce training suggests that future funding for global health
      education should prioritize such south-south collaborations.

PMID- 25588888
TI  - Breastfeeding.

PMID- 25588890
TI  - Interest of high-definition optical coherent tomography (HD-OCT) for non-invasive
      imaging of dermatofibroma: a pilot study.

PMID- 25588889
TI  - Distribution of yeast isolates from invasive infections and their in vitro
      susceptibility to antifungal agents: evidence from 299 cases in a 3-year (2010 to
      2012) surveillance study.
AB  - Invasive yeast infections cause significant morbidity and mortality. Surveillance
      for the infection is necessary to detect trends in species distribution and
      antifungal resistance. We performed this retrospective study of yeast infection
      at Jinling Hospital, Nanjing in China, from year of 2010 to 2012. A total of 341
      yeast isolates were obtained from patients with invasive infections in the
      period. Among these isolates, Candida spp. comprised of the highest percentage of
      yeast strains (91.8 %), followed by Cryptococcus neoformans (5.9 %) and other non
      Candida yeast strains (2.3 %). Bloodstream isolates made up 41.3 % of yeast
      strains and the isolates from CVC made up 17.3 %. Among Candida spp., C. albicans
      was the most common species identified from non-blood clinical specimens (42.9
      %), but appeared in only 20.8 % of blood isolates (P < 0.001). C. tropicalis was
      the most prevalent Candida species in the blood samples (28.5 %). Candida spp.
      was mainly isolated from specimens of the ICU patients, while C. neoformans was
      mainly isolated from specimens in medical wards. Resistance to FLC occurred in
      3.7 % of C. albicans, 9.9 % of C. tropicalis, 74.0 % of C. glabrata, and 4.4 % of
      C. parapsilosis. Most (>92 %) isolates of C. albicans, C. tropicalis, C.
      parapsilosis, and C. neoformans strains were susceptible to VRC; However, 26.7 %
      of isolates of C. glabrata were VRC resistant.

PMID- 25588891
TI  - Discovery of Novel 2-(piperidin-4-yl)-1H-benzo[d]imidazole Derivatives as
      Potential Anti-Inflammatory Agents.
AB  - A novel 2-(piperidin-4-yl)-1H-benzo[d]imidazole derivative 5 with good anti
      inflammatory activity was identified from our in-house library. Based on hit
      compound 5, two series of 2-(piperidin-4-yl)-1H-benzo[d]imidazole derivative 6a-g
      and 7a-h were designed and synthesized as novel anti-inflammatory agents. Most of
      synthesized compounds exhibited good inhibitory activity on NO and TNF-alpha
      production in LPS-stimulated RAW 264.7 macrophages, in which the compound 6e
      showed most potent inhibitory activity on NO (IC50  = 0.86 MUm) and TNF-alpha
      (IC50  = 1.87 MUm) production. Further evaluation revealed that compound 6e
      displayed more potent in vivo anti-inflammatory activity than ibuprofen did on
      xylene-induced ear oedema in mice. Additionally, Western blot analysis revealed
      that compound 6e could restore phosphorylation level of IkappaBalpha and protein
      expression of p65 NF-kappaB in LPS-stimulated RAW 264.7 macrophages. 

PMID- 25588893
TI  - Measurement of human rotation behavior for psychological and neuropsychological
      investigations.
AB  - The investigation of rotation behavior in human beings enjoys a longstanding and
      enduring interest in laterality research. While in animal studies the issue of
      accurately measuring the number of rotations has been solved and is widely
      applied in practice, it is still challenging to assess the rotation behavior of
      humans in daily life. We propose a robust method to assess human rotation
      behavior based on recordings from a miniature inertial measurement unit that can
      be worn unobtrusively on a belt. We investigate the effect of different
      combinations of low-cost sensors-including accelerometers, gyroscopes, and
      magnetometers-on rotation measurement accuracy, propose a simple calibration
      procedure, and validate the method on data from a predefined path through and
      around buildings. Results suggest that a rotation estimation based on the fusion
      of accelerometer, gyroscope, and magnetometer measurements outperforms methods
      based solely on earth magnetic field measurements, as proposed in previous
      studies, by a drop in error rate of up to 32 %. We further show that magnetometer
      signals do not significantly contribute to measurement accuracy in short-term
      measurements, and could thus be omitted for improved robustness in environments
      with magnetic field disturbances. Results also suggest that our simple
      calibration procedure can compete with more complex approaches and reduce the
      error rate of the proposed algorithm by up to 38 %. 

PMID- 25588892
TI  - Nencki Affective Word List (NAWL): the cultural adaptation of the Berlin
      Affective Word List-Reloaded (BAWL-R) for Polish.
AB  - In the present article, we introduce the Nencki Affective Word List (NAWL),
      created in order to provide researchers with a database of 2,902 Polish words,
      including nouns, verbs, and adjectives, with ratings of emotional valence,
      arousal, and imageability. Measures of several objective psycholinguistic
      features of the words (frequency, grammatical class, and number of letters) are
      also controlled. The database is a Polish adaptation of the Berlin Affective Word
      List-Reloaded (BAWL-R; Vo et al., Behavior Research Methods 41:534-538, 2009),
      commonly used to investigate the affective properties of German words. Affective
      normative ratings were collected from 266 Polish participants (136 women and 130
      men). The emotional ratings and psycholinguistic indexes provided by NAWL can be
      used by researchers to better control the verbal materials they apply and to
      adjust them to specific experimental questions or issues of interest. The NAWL is
      freely accessible to the scientific community for noncommercial use as
      supplementary material to this article. 

PMID- 25588896
TI  - Is exaggeration in academic press releases related to investigators' conflicts of
      interests?

PMID- 25588894
TI  - The electromyographic threshold in boys and men.
AB  - BACKGROUND: Children have been shown to have higher lactate (LaTh) and
      ventilatory (VeTh) thresholds than adults, which might be explained by lower
      levels of type-II motor-unit (MU) recruitment. However, the electromyographic
      threshold (EMGTh), regarded as indicating the onset of accelerated type-II MU
      recruitment, has been investigated only in adults. PURPOSE: To compare the
      relative exercise intensity at which the EMGTh occurs in boys versus men.
      METHODS: Participants were 21 men (23.4 +/- 4.1 years) and 23 boys (11.1 +/- 1.1
      years), with similar habitual physical activity and peak oxygen consumption
      (VO2pk) (49.7 +/- 5.5 vs. 50.1 +/- 7.4 ml kg(-1) min(-1), respectively). Ramped
      cycle ergometry was conducted to volitional exhaustion with surface EMG recorded
      from the right and left vastus lateralis muscles throughout the test (~10 min).
      The composite right-left EMG root mean square (EMGRMS) was then calculated per
      pedal revolution. The EMGTh was then determined as the exercise intensity at the
      point of least residual sum of squares for any two regression line divisions of
      the EMGRMS plot. RESULTS: EMGTh was detected in 20/21 of the men (95.2 %) and
      only in 18/23 of the boys (78.3 %). The boys' EMGTh was significantly higher than
      the men's (86.4 +/- 9.6 vs. 79.7 +/- 10.0 % of peak power output at exhaustion; p
      < 0.05). The pattern was similar when EMGTh was expressed as percentage of VO2pk.
      CONCLUSIONS: The boys' higher EMGTh suggests delayed and hence lesser utilization
      of type-II MUs in progressive exercise, compared with men. The boys-men EMGTh
      differences were of similar magnitude as those shown for LaTh and VeTh, further
      suggesting a common underlying factor.

PMID- 25588897
TI  - Macular pigment optical density in a healthy Chinese population.
AB  - PURPOSE: To measure the macular pigment optical density (MPOD) values in a
      healthy Chinese population using the one-wavelength reflectometry method and to
      investigate the relationships of MPOD with age, sex, body mass index (BMI),
      smoking and lens opacities. METHODS: A total of 441 healthy participants, aged 3
      81 years old (242 male and 199 female subjects), were enrolled in this study.
      Demographic and lifestyle data were recorded based on physical examinations and
      questionnaires. Lens opacities were measured according to the Lens Opacities
      Classification System III (LOCS III). MPOD values were measured at 7 degrees  of
      eccentricity, using the one-wavelength reflectometry method (Visucam 200; Carl
      Zeiss Meditec). MPOD values were reported in parameters including 'max' and
      'mean' optical density (OD). The original MPOD values without automated
      correction were used for analysis. RESULTS: The average values were 0.303 +/-
      0.097 d.u. (initials of density units) for the max OD and 0.109 +/- 0.031 d.u.
      for the mean OD. A significant inverse relationship was found between age and
      MPOD (for max OD, beta = -0.716, p < 0.001; for mean OD, beta = -0.669, p <
      0.001). Participants with no lens opacities had higher MPOD values than those
      with moderate lens opacities (p < 0.001). The MPOD values were not associated
      with sex, BMI or smoking status. CONCLUSION: MPOD within 7 degrees  of
      eccentricity, as measured by one-wavelength reflectometry, was found to decrease
      with increasing age in a healthy Chinese population, and lens opacities had an
      impact on these measurements. These results provide a reference value for future
      studies in the Chinese population.

PMID- 25588899
TI  - A survey of anthropometry of rural agricultural workers in Enugu State, south
      eastern Nigeria.
AB  - In developed countries, large amount of anthropometric data are available for
      reference purposes; however, anthropometric data of Nigerian populace are
      lacking. As a result, most agricultural machines and equipment used are designed
      using anthropometric data from other populations of the world. A total of 377
      rural agricultural workers within the age limit of 18-45 years, who are involved
      in different agricultural activities, were selected from six rural agriculture
      based communities in Enugu state. Thirty-six anthropometric body dimensions were
      measured including age and body weight. A comparison between the male and female
      data indicated that data obtained from male agricultural workers were higher than
      that obtained from their female counterparts in all body dimensions except chest
      (bust) depth, abdominal breadth and hip breadth (sitting). In terms of design
      parameters, it was observed that the data from Nigerian agricultural workers were
      different from that obtained from agricultural workers in north-eastern India.
      Practitioner Summary. Anthropometric data of Nigeria populace are lacking. As a
      result, most agricultural machines and equipment used are designed using
      anthropometric data from other populations of the world. It was observed that the
      data from Nigerian agricultural workers were different from that obtained from
      agricultural workers in north-eastern India. 

PMID- 25588900
TI  - John Appleby: hoping for the "Appleby paradox".

PMID- 25588898
TI  - Identification of molecular signature of head and neck cancer stem-like cells.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer
      in the world. HNSCC remains difficult to treat, and despite advances in
      treatment, overall survival rate has modestly improved over the past several
      years. Poor survival rate is attributed to high frequency of local recurrence and
      distant metastasis. Cancer stem-like cells (CSCs) have been implicated in tumor
      recurrence and confer resistance to anti-cancer therapy treatment. In this study,
      we have characterized genes that are modulated in HNSCC-CSCs and can be targeted
      in future as potential therapeutics. CSCs were isolated from HNSCC cells
      (oralspheres) and examined for tumorigenicity in immunodeficient mice. We
      observed aggressive tumor growth with oralspheres as compared to parental cells.
      The CSC-derived tumors were grossly extremely vascularized and expressed VEGFR1.
      We next analyzed the molecular determinant of oralspheres. In addition to CD133
      and Nanog, we observed significant higher expression of Notch1 protein in the
      oralspheres. There was differential expression of angiogenesis and invasive
      marker genes such as angiopoietin1, integrin beta3, MMP9 and THBS1.
      Interestingly, c-Fos was upregulated in oralspheres as compared to parental
      cells. Our observations suggest that understanding the molecular determinant of
      oralspheres will help in developing future therapeutic modalities against
      treatment resistant HNSCC. 

PMID- 25588901
TI  - Feasibility, efficacy, and safety of radiofrequency ablation of atrial
      fibrillation guided by monitoring of the initial impedance decrease as a
      surrogate of catheter contact.
AB  - BACKGROUND: The initial impedance decrease during radiofrequency (RF) ablation is
      an indirect marker of catheter contact and lesion formation. We aimed to assess
      feasibility, efficacy, and safety of an ablation approach guided by initial
      impedance decrease. METHODS: A total of 25 patients with paroxysmal AF had point
      by-point, wide antral pulmonary vein (PV) isolation. RF applications were aborted
      if a decrease of at least 5 Omega did not occur in the first 10 seconds;
      otherwise, ablation was continued for at least 20 seconds. Power was 30 Watts and
      reduced to 15-25 Watts on the posterior wall. RESULTS: A total of 28% of RF
      applications were terminated because of inadequate impedance decrease. The
      remaining lesions showed a median decrease of 7.6 Omega (IQR 5.0-10.7) at 10
      seconds and median duration of RF lesions was 38 seconds. Note that, 100 PVs were
      isolated with 49 rings. PVI occurred before anatomic completion of the ablation
      ring of adequate lesions in 39/49 (80%) and concurrent with ring completion in
      7/49 (14%). Additional lesions were required in 3/49 (6%) rings. After PVI,
      additional lesions were required to eliminate dormant conduction in 2/47 (4%) and
      pace-capture on the ablation line in 24/49 vein pairs (49%). During short-term
      follow-up, 3 nonfatal esophageal injuries and 2 late pericardial effusions
      occurred. During a mean follow-up of 431 +/- 87 days, 21/25 patients (84%)
      remained free of recurrent symptomatic atrial arrhythmias. CONCLUSIONS: PVI
      guided by initial impedance decrease is feasible and results in PVI concurrent
      with or before completion of the ablation ring in 94% of patients. Single
      procedure efficacy after one year of follow-up was 84%. Near-term complications
      suggest that deeper lesions are created, indicating that further reduction of RF
      power and duration is warranted.

PMID- 25588902
TI  - Induction of clinical and colonoscopic remission of mild-to-moderate ulcerative
      colitis with budesonide MMX 9 mg: pooled analysis of two phase 3 studies.
AB  - BACKGROUND: Conventional oral corticosteroids are effective at reducing
      inflammation associated with ulcerative colitis (UC); however, systemic adverse
      effects limit their use. Budesonide MMX is an extended-release, second-generation
      corticosteroid that targets delivery of budesonide to the entire colon. AIM: To
      analyse efficacy and safety outcomes from two phase 3 studies of budesonide MMX
      in patients with mild-to-moderate active UC. METHODS: Patients were assigned to
      budesonide MMX 9 mg, budesonide MMX 6 mg, or placebo once daily in two
      randomised, double-blind, placebo-controlled, 8-week studies (CORE I and II).
      Pooled data were analysed for pre-defined primary (combined clinical and
      colonoscopic remission), secondary and exploratory endpoints. Primary endpoint
      data were analysed to evaluate the potential influence of demographical and
      baseline disease characteristics on remission. RESULTS: Modified intent-to-treat
      population (histological evidence of baseline inflammation) had 232, 230 and 210
      patients in budesonide MMX 9 mg, budesonide MMX 6 mg and placebo groups
      respectively. Combined clinical and colonoscopic remission rates were
      significantly greater than placebo (6.2%) for the budesonide MMX 9 mg group
      (17.7%; P = 0.0002), but not the budesonide MMX 6 mg group (10.9%). The primary
      endpoint of remission with budesonide MMX 9 mg was significantly greater than
      placebo in most subgroups analysed. Symptom resolution and colonoscopic
      improvement rates were significantly greater with budesonide MMX 9 mg vs.
      placebo. Budesonide MMX was safe and well tolerated. CONCLUSION: This pooled
      analysis showed that budesonide MMX 9 mg is efficacious, safe and well tolerated
      for inducing remission of mild-to-moderate UC.

PMID- 25588903
TI  - Welfare measurements of finishing pigs on the day of slaughter: a review.
AB  - Animal welfare on the day of slaughter is of increasing concern to the
      authorities and consumers alike, creating a need not only to optimize the welfare
      of the animals but also to document the level of welfare. The day of slaughter is
      composed of a variety of stages, initiated when the pigs leave the home pen and
      including pick-up facilities, transport, lairage, stunning and sticking. At each
      of these stages, the animals are exposed to different stressors that, both
      individually and in interaction with one another, can compromise welfare. As part
      of the initial work aiming to document the welfare of finishing pigs on the day
      of slaughter, this paper provides an overview of the individual stages including
      a discussion of potential stressors and potential welfare measurements. These
      measurements are discussed with regard to their relevance and suitability for
      documentation of animal welfare on the day of slaughter for development of on
      site tools for continuous automatic monitoring of animal welfare. 

PMID- 25588904
TI  - Tracheobronchial fistula during the perioperative period of esophagectomy for
      esophageal cancer.
AB  - BACKGROUND: Tracheobronchial (TB) injury and fistula formation during the
      perioperative period of esophagectomy is a rare but life-threatening
      complication. METHODS: We examined the development of intraoperative TB injury
      and postoperative TB fistulas in consecutive 763 patients with esophageal cancer
      who underwent esophagectomy, including 494 patients who underwent transthoracic
      subtotal esophagectomy. RESULTS: TB injury and fistulas developed in two (0.4 %)
      and four patients (0.8 %), respectively, who received transthoracic
      esophagectomy. TB injury developed during the dissection of a tumor invading a
      major airway. Direct suturing of the laceration and covering it using a muscle
      flap was effective for one patient, while additional repair with a major pectoral
      muscle flap was needed in another patient. Postoperative TB fistulas developed
      due to peri-tracheal infection in two patients, and conservative treatment with
      drainage was performed. In another two patients, gastro-tracheal fistulas
      developed due to mechanical compression of staplers on the gastric tube, which
      was elevated via the posterior mediastinal route. The direct repair of the
      gastric tube and covering it with a major pectoral muscle flap resulted in the
      resolution of these fistulas. CONCLUSION: Careful dissection with direct vision
      of the esophagus, as well as oversewing of the staplers on the gastric tube, is
      mandatory for preventing TB injury and fistula formation. Appropriate drainage is
      effective in cases with peri-tracheal abscesses. If the TB fistula fails to heal
      within a 4- to 6-week period, conservative management should be abandoned. Direct
      surgical intervention with coverage by a muscle flap is important for TB
      fistulas.

PMID- 25588905
TI  - Conformational features and binding affinities to Cripto, ALK7 and ALK4 of Nodal
      synthetic fragments.
AB  - Nodal, a member of the TGF-beta superfamily, is a potent embryonic morphogen also
      implicated in tumor progression. As for other TGF-betas, it triggers the
      signaling functions through the interaction with the extracellular domains of
      type I and type II serine/threonine kinase receptors and with the co-receptor
      Cripto. Recently, we reported the molecular models of Nodal in complex with its
      type I receptors (ALK4 and ALK7) as well as with Cripto, as obtained by homology
      modeling and docking simulations. From such models, potential binding epitopes
      have been identified. To validate such hypotheses, a series of mutated Nodal
      fragments have been synthesized. These peptide analogs encompass residues 44-67
      of the Nodal protein, corresponding to the pre-helix loop and the H3 helix, and
      reproduce the wild-type sequence or bear some modifications to evaluate the hot
      spot role of modified residues in the receptor binding. Here, we show the
      structural characterization in solution by CD and NMR of the Nodal peptides and
      the measurement of binding affinity toward Cripto by surface plasmon resonance.
      Data collected by both conformational analyses and binding measurements suggest a
      role for Y58 of Nodal in the recognition with Cripto and confirm that previously
      reported for E49 and E50. Surface plasmon resonance binding assays with
      recombinant proteins show that Nodal interacts in vitro also with ALK7 and ALK4
      and preliminary data, generated using the Nodal synthetic fragments, suggest that
      Y58 of Nodal may also be involved in the recognition with these protein partners.

PMID- 25588906
TI  - Reproducibility of pharmacological ASL using sequences from different vendors:
      implications for multicenter drug studies.
AB  - OBJECT: The current study assesses the multicenter feasibility of pharmacological
      arterial spin labeling (ASL) by comparing a caffeine-induced relative cerebral
      blood flow decrease (%CBF?) measured with two pseudo-continuous ASL sequences as
      provided by two major vendors. MATERIALS AND METHODS: Twenty-two healthy
      volunteers were scanned twice with both a 3D spiral (GE) and a 2D EPI (Philips)
      sequence. The inter-session reproducibility was evaluated by comparisons of the
      mean and within-subject coefficient of variability (wsCV) of the %CBF?, both for
      the total cerebral gray matter and on a voxel level. RESULTS: The %CBF? was
      larger when measured with the 3D spiral sequence (23.9 +/- 5.9 %) than when
      measured with the 2D EPI sequence (19.2 +/- 5.6 %) on a total gray matter level
      (p = 0.02), and on a voxel level in the posterior watershed area (p < 0.001).
      There was no difference between the gray matter wsCV of the 3D spiral (57.3 %)
      and 2D EPI sequence (66.7 %, p = 0.3), whereas on a voxel level, the wsCV was
      visibly different between the sequences. CONCLUSION: The observed differences
      between ASL sequences of both vendors can be explained by differences in the
      employed readout modules. These differences may seriously hamper multicenter
      pharmacological ASL, which strongly encourages standardization of ASL
      implementations.

PMID- 25588909
TI  - Unravelling the quenching mechanisms of a luminescent Ru(II) probe for Cu(II).
AB  - We have investigated the photophysical and photochemical features of a
      luminescent heteroleptic Ru(II)-polypyridyl probe and of its corresponding Ru(II)
      Cu(II) dinuclear complex formed upon the analyte binding through extensive
      density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. The
      molecular probe contains the tailored imidazo[4,5-f]-1,10-phenanthroline (IIP)
      ligand for simultaneously binding the Ru(II) core and the target metal ion in
      aqueous solution. We have rationalized the static photoluminescence quenching
      observed upon the Cu(II) coordination, on the grounds of distinct excited state
      deactivation mechanisms which are absent in the free Ru(II) complex probe.
      Additionally, the emission quenching found upon increasing the solution pH has
      also been investigated. When coordinated IIP deprotonates, the nature of the
      lowest excited state of its complex changes from (3)MLCT to (3)LLCT/(3)IL. The
      strong base-induced emission quenching can be understood in terms of both the
      energy-gap law, since the (3)LLCT/(3)IL states lie at a significantly lower
      energy than the (3)MLCT state increasing the contribution of non-radiative
      mechanisms, and the expected slower radiative rates from such (3)LLCT/(3)IL
      states. After Cu(II) binding, the lowest triplet excited state is similar to the
      analyte-free probe in both energy and electronic nature. However, Cu-centered non
      radiative excited states, populated after photoinduced electron transfer and
      intersystem crossing processes, are responsible for the population drainage of
      the emissive state.

PMID- 25588908
TI  - Laparoscopic reconstruction of an iatrogenic perforation of the neovagina and
      urinary bladder by a neovaginal dilator in a patient with Mayer-Rokitansky-Kuster
      Hauser syndrome.
AB  - INTRODUCTION AND HYPOTHESIS: Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is a
      rare genital aplasia syndrome. Patients with MRKH regularly dilate their
      neovagina with vaginal dilatators. METHODS: A 23-year-old MRKH syndrome patient
      came to our department complaining of a lost vaginal dilator, which she had
      inserted 2 days previously. She had no bleeding or abdominal pain, but did have
      occasional urine loss. She had a history of abdominal exploration for an acute
      abdomen and the creation of a neovagina at the age of 16. An abdominal CT scan
      located the dislocated dilator intravesically. After diagnostic laparoscopy, the
      dilator was removed through the vesico-neovaginal perforation. The vagina was
      closed and covered by a pedicled peritoneal flap, followed by closure of the
      urinary bladder. An omental J-flap was then fixed between the vagina and bladder.
      RESULTS: The operative time was 185 min, with no significant blood loss, injuries
      or need for conversion/revision. The indwelling catheter was removed 7 days later
      after cystography, followed by normal micturition and an adequate bladder
      capacity. Vaginal dilation and sexual activity was resumed 1 month
      postoperatively. Follow-up was uneventful. CONCLUSIONS: Laparoscopic vaginal
      dilator removal with immediate repair of the perforation of the neovagina and the
      urinary bladder directly after an acute trauma in a patient with MRKH syndrome
      may be a management option. It is a feasible, safe and viable operation in the
      hands of experienced laparoscopists.

PMID- 25588907
TI  - Evaluating the effects of increasing physical activity to optimize rehabilitation
      outcomes in hospitalized older adults (MOVE Trial): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Older adults who have received inpatient rehabilitation often have
      significant mobility disability at discharge. Physical activity levels in
      rehabilitation are also low. It is hypothesized that providing increased physical
      activity to older people receiving hospital-based rehabilitation will lead to
      better mobility outcomes at discharge. METHODS/DESIGN: A single blind, parallel
      group, multisite randomized controlled trial with blinded assessment of outcome
      and intention-to-treat analysis. The cost effectiveness of the intervention will
      also be examined. Older people (age >60 years) undergoing inpatient
      rehabilitation to improve mobility will be recruited from geriatric
      rehabilitation units at two Australian hospitals. A computer-generated blocked
      stratified randomization sequence will be used to assign 198 participants in a
      1:1 ratio to either an 'enhanced physical activity' (intervention) group or a
      'usual care plus' (control) group for the duration of their inpatient stay.
      Participants will receive usual care and either spend time each week performing
      additional physical activities such as standing or walking (intervention group)
      or performing an equal amount of social activities that have minimal impact on
      mobility such as card and board games (control group). Self-selected gait speed
      will be measured using a 6-meter walk test at discharge (primary outcome) and 6
      months follow-up (secondary outcome). The study is powered to detect a 0.1 m/sec
      increase in self-selected gait speed in the intervention group at discharge.
      Additional measures of mobility (Timed Up and Go, De Morton Mobility Index),
      function (Functional Independence Measure) and quality of life will be obtained
      as secondary outcomes at discharge and tertiary outcomes at 6 months follow-up.
      The trial commenced recruitment on 28 January 2014. DISCUSSION: This study will
      evaluate the efficacy and cost effectiveness of increasing physical activity in
      older people during inpatient rehabilitation. These results will assist in the
      development of evidenced-based rehabilitation programs for this population. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000884707
      (Date of registration 08 August 2013); ClinicalTrials.gov Identifier NCT01910740
      (Date of registration 22 July 2013).

PMID- 25588910
TI  - Synthesis and Photophysical Properties of Two Diazaporphyrin-Porphyrin Hetero
      Dimers in Polar and Nonpolar Solutions.
AB  - Two diazaporphyrin (DAP)-porphyrin hetero dimers, in beta-meso and beta-beta
      configurations, were prepared to study their photoinduced intramolecular electron
      transfer properties. The two meso nitrogen atoms in the porphyrin ring of DAP
      change its redox potential, making DAP more easily reduced, compared to its
      porphyrin counterpart. A charge-transfer from porphyrin to DAP in both hetero
      dimers was verified by versatile optical spectroscopic methods. The steady-state
      fluorescence spectra indicated an efficient intramolecular exciplex formation for
      both dimers. For the beta-meso dimer, ultrafast time-resolved spectroscopic
      methods revealed the subpicosecond formation of two types of primary short-living
      (1-18 ps) intramolecular exciplexes, which relaxed in toluene to form a long
      living final exciplex (1.4 ns) followed by a longer-living charge transfer
      complex (>5 ns). However, in benzonitrile, the lifetime of the final exciplex was
      longer (660 ps) as was that of the charge transfer complex (180 ps). The beta
      beta analogue formed similar short-living exciplexes in both solvents, but the
      final exciplex and the charge transfer state had significantly shorter lifetimes.
      The electrochemical redox potential measurements and density functional theory
      calculations supported the proposed mechanism. 

PMID- 25588911
TI  - Provider advice on exercise and diet among adults with comorbid serious
      psychological distress and diabetes or diabetes risk factors.
AB  - PURPOSE: To examine the lifetime prevalence and correlates of provider advice to
      increase exercise and reduce dietary fat intake among adults with comorbid
      serious psychological distress (SPD) and diabetes or diabetes risk factors.
      METHODS: Study sample (n = 5942) was selected from the Medical Expenditure Panel
      Survey Household Component (MEPS-HC) series of 2007-2011. SPD was defined as a
      score of >=13 on the Kessler Psychological Distress Scale (K6). Multivariate
      logistic regression was used to examine correlates of lifetime provider advice.
      RESULTS: Less than half of adults with SPD had been advised to increase exercise
      (49.4%) or reduce dietary fat intake (45.6%). The prevalence of receiving
      provider advice increased in a linear fashion as the number of diabetes risk
      factors increased and was the highest among those with diabetes. Provision of
      provider advice was strongly associated with clinical factors rather than
      individuals' sociodemographic characteristics and current health behaviors.
      CONCLUSIONS: Health care providers are missing opportunities to provide exercise
      and low-fat dietary advice to patients with SPD before they manifest clinical
      risk factors associated with diabetes. It is important that providers counsel
      them as early as possible about exercise and nutritional changes that reduce the
      risks associated with diabetes.

PMID- 25588913
TI  - Population-based healthcare: the experience of a regional health system.

PMID- 25588914
TI  - Clinician scientists in public sector hospitals--why and how?

PMID- 25588915
TI  - Oncologic outcomes of neoadjuvant chemoradiation for locally advanced rectal
      cancer: a single-institution experience.
AB  - INTRODUCTION: This study reports the outcomes of patients with locally advanced
      rectal cancer treated with neoadjuvant chemoradiation followed by surgery in a
      local population of Singapore. MATERIALS AND METHODS: The records of 85 patients
      who underwent neoadjuvant chemoradiation for locally advanced rectal cancer
      followed by surgery at the Tan Tock Seng Hospital (TTSH) between November 2002
      and January 2012 were reviewed. The treatment protocol comprised radiotherapy to
      a total dose of 50.4 Gy concurrent with 5-fluorouracil-based chemotherapy.
      Patients underwent total mesorectal excision surgery following the completion of
      neoadjuvant chemoradiation. Local control, disease-free survival and overall
      survival were analysed using Kaplan-Meier methods. RESULTS: Median age of the
      patients was 61 years. All of them completed radiotherapy. One patient did not
      complete neoadjuvant chemotherapy. The median time to surgery was 52 days. Fifty
      five percent (47 of 85) of patients achieved pathological downstaging and 13% (11
      of 85) of patients had a pathologic complete response to preoperative treatment.
      The neoadjuvant chemoradiation was well tolerated. Four percent of patients had
      grade 3 diarrhoea and 4% of them had grade 3 dermatitis. There were no grade 4
      toxicities. With a median follow-up of 41 months, the 5-year actuarial local
      recurrence, disease-free survival and overall survival rates were 7%, 71.9%, and
      83.2% respectively. Univariate analysis showed that patients with positive
      surgical margins had significantly worse disease-free survival and overall
      survival (P=0.012 and P<0.001 respectively) and a trend towards a higher rate of
      local recurrence (P=0.08). CONCLUSION: Our study provides evidence that
      neoadjuvant chemoradiation is an effective treatment for locally advanced rectal
      cancer. Our outcomes are comparable with internationally published data and
      demonstrate the reproducibility of the neoadjuvant approach in an Asian
      population.

PMID- 25588912
TI  - Skilled forelimb movements and internal copy motor circuits.
AB  - Mammalian skilled forelimb movements are remarkable in their precision, a feature
      that emerges from the continuous adjustment of motor output. Here we discuss
      recent progress in bridging the gap between theory and neural implementation in
      understanding the basis of forelimb motor refinement. One influential theory is
      that feedback from internal copy motor pathways enables fast prediction, through
      a forward model of the limb, an idea supported by behavioral studies that have
      explored how forelimb movements are corrected online and can adapt to changing
      conditions. In parallel, neural substrates of forelimb internal copy pathways are
      coming into clearer focus, in part through the use of genetically tractable
      animal models to isolate spinal and cerebellar circuits and explore their
      contributions to movement. 

PMID- 25588916
TI  - Association of Socioeconomic Status (SES) and Social Support with Depressive
      Symptoms among the Elderly in Singapore.
AB  - INTRODUCTION: Depression in the elderly is a major public health issue.
      Socioeconomic status (SES) and social support are strong risk factors for
      depression. This study aimed to investigate the influence of SES and social
      support in elderly depression, and the modifying effect of social support on the
      relationship between SES and depression. MATERIALS AND METHODS: A community-based
      survey was conducted on residents>=60 years old. Depressive symptoms were
      determined with scores>=5 using the 15-item Geriatric Depression Scale (GDS).
      Multivariable logistic regression was performed to determine the odds ratio (OR)
      of depressive symptoms with respect to SES and social support, and interaction
      terms between the two variables. RESULTS: Of 2447 responses analysed, 188 (7.8%)
      respondents had depressive symptoms. Living in 2-room housing, living alone/with
      a domestic helper, infrequent leisure time with children/grandchildren or being
      childless, and feeling socially isolated were independently associated with
      depressive symptoms. Relative to residents living with spouse and children in 4
      /5-room housing, the highest ORs for depressive symptoms were those living with
      spouse and children in 2-room (OR: 3.06, P<0.05), followed by living with
      children only in 3-room (OR: 2.98, P<0.05), and living alone/with a domestic
      helper in 4-/5-room (OR: 2.73, P<0.05). Living with spouse only appears to buffer
      against depressive symptoms across socioeconomic classes, although the effect was
      not statistically significant. CONCLUSION: Low social support and low SES
      significantly increased the odds of depressive symptoms. The moderating effect of
      social support on depression was however not consistent across SES groups.
      Specific interventions need to target different SES groups to better help older
      adults at risk of developing depression.

PMID- 25588917
TI  - Overcoming Barriers to Mammography Screening: A Quasi-randomised Pragmatic Trial
      in a Community-based Primary Care Setting.
AB  - INTRODUCTION: Breast cancer is the leading cancer among women in Singapore. Five
      years after a population-wide breast cancer screening programme was introduced,
      screening rates remained relatively low at 41%. Studies have shown decreased
      screening propensity among medically underserved women typically of minority or
      socioeconomically disadvantaged status. We conducted a quasi-randomised pragmatic
      trial aimed at encouraging mammography screening among underscreened or
      unscreened women in a publicly funded primary care facility in Singapore.
      MATERIALS AND METHODS: The study was conducted from May to August 2010.
      Components of intervention included (1) tailored education, (2) doctor's
      reminder, and (3) cost reduction. Researchers administered a structured
      questionnaire to eligible female polyclinic attendees and patient companions aged
      40 to 69 years. Individual knowledge, attitudes, beliefs, and barriers towards
      mammography screening were identified and educational messages tailored. Doctor's
      reminder and cost reduction were implemented additively. RESULTS: Overall, out of
      448 participants, 87 (19.4%, 95% confidence interval (CI), 15.8% to 23.1%)
      completed mammography screening across 3 arms of study. Participants who received
      a cost reduction were more likely to attend screening compared to participants in
      other intervention arms (adjusted odds ratio (OR) 2.4, 95% CI, 1.2 to 4.5, P =
      0.009). Cost of screening, ethnicity, prior screening history, and attitudes
      towards mammography screening were identified as significant factors predicting
      mammogram attendance. CONCLUSION: Including a cost reduction component was the
      most effective intervention that increased mammography screening rates. Women's
      underlying beliefs, attitudes, and other predisposing factors should also be
      considered for integration into existing breast cancer screening programmes.

PMID- 25588918
TI  - Physiologically-guided Balanced Resuscitation: An Evidence-based Approach for
      Acute Fluid Management in Paediatric Major Trauma.
AB  - Trauma is a major cause of death, and haemorrhage represents an important target
      for improving outcomes after severe injury. Volume replacement with crystalloids
      in resuscitation might become harmful in large amounts because of coagulopathy. A
      fine balance must be achieved between haemodynamic and haemostatic resuscitation.
      Permissive hypotension refers to permitting some degree of hypotension in such
      adult patients in an attempt to attain this fine balance. For patients who
      require a significant volume of blood product resuscitation, the term 'massive
      transfusion protocol' (MTP) is used. There is very little data on transfusion
      protocols for paediatric trauma patients, and children respond to hypovolemic
      shock in a different physiological manner compared to adults. Hence, concepts
      such as permissive hypotension may not be appropriate when treating children
      involved in major trauma. We recently embarked on a plan to streamline the
      management of blood transfusion in massive bleeding during paediatric trauma, to
      reduce the logistical problems associated with the transport of blood products
      from the blood bank to the patient. From this, we evolved a MTP for paediatric
      major trauma. Nonetheless, further studies will be needed to see if there is
      indeed improved outcome after MTP in paediatric major trauma as current evidence
      is extrapolated from adult studies. 

PMID- 25588919
TI  - Probing the brain white matter in psychotic disorders using neuroimaging.

PMID- 25588921
TI  - The mechanism of a ligand-promoted C(sp3)-H activation and arylation reaction via
      palladium catalysis: theoretical demonstration of a Pd(II)/Pd(IV) redox manifold.
AB  - Density functional theory (DFT) computations (BP86 and M06-L) have been utilized
      to elucidate the detailed mechanism of a palladium-catalyzed reaction involving
      pyridine-type nitrogen-donor ligands that significantly expands the scope of
      C(sp(3))-H activation and arylation. The reaction begins with precatalyst
      initiation, followed by substrate binding to the Pd(II) center through an amidate
      auxiliary, which directs the ensuing bicarbonate-assisted C(sp(3))-H bond
      activation producing five-membered-ring cyclopalladate(II) intermediates. These
      Pd(II) complexes further undergo oxidative addition with iodobenzene to form
      Pd(IV) complexes, which proceed by reductive C-C elimination/coupling to give
      final products of arylation. The base-assisted C(sp(3))-H bond cleavage is found
      to be the rate-determining step, which involves hydrogen bond interactions. The
      mechanism unravels the intimate involvement of the added 2-picoline ligand in
      every phase of the reaction, explains the isolation of the cyclopalladate
      intermediates, agrees with the observed kinetic hydrogen isotope effect, and
      demonstrates the Pd(II)/Pd(IV) redox manifold. 

PMID- 25588920
TI  - A questionnaire survey of pediatric inflammatory bowel disease in India.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is not uncommon in children and is
      an important cause of morbidity. Since information on IBD in Indian children is
      sparse, the study aimed at highlighting the salient features in them. MATERIALS
      AND METHODS: A questionnaire survey was done among 221 children and adolescents
      with IBD [ulcerative colitis (UC) 93 (42.1 %); Crohn's disease (CD) 122 (55.2 %);
      unclassified (IBD-U) 6 (2.7 %)] across seven centers in India. The cut-off age
      was 18 years and below. RESULTS: The mean age of presentation for UC and CD was
      10.2 +/- 4.4 and 11.0 +/- 4.5 years, respectively, with no gender difference.
      Diarrhea (69.9 %, p = 0.001) and blood in the stools (90.3 %, p = 0.0001) were
      common in UC, whereas abdominal pain (73.8 %, p = 0.01), fever (39.3 %, p =
      0.0001), anemia (64.7 %, p = 0.001), and growth failure (76.2 %, p = 0.0001) were
      common in CD. Extraintestinal manifestations (EIM) were a feature in 23.6 % and
      36.1 % of UC and CD, respectively. Pancolitis (E3) was predominant in UC (70.9 %)
      and 88 % required steroids. Ileocolonic CD (L3) was common in 72.9 %; 76.2 %
      required azathioprine for maintenance. Of the children with UC, 11.8 % had
      complications like massive hemorrhage and toxic megacolon, while 27 % of CD had
      fistulae, perianal abscess, stricture, and perforation. Biologicals were used in
      0.8 % of severe UC and in 12.2 % of CD. In UC, 4.3 % required surgical
      intervention. CONCLUSION: Pediatric inflammatory bowel disease (P-IBD) in India
      shares similarities with adult-onset IBD. Distinctive features were growth
      failure and more severe forms of the disease necessitating immunomodulators.

PMID- 25588922
TI  - An evaporation-induced tri-consistent assembly route towards nitrogen-doped
      carbon microfibers with ordered mesopores for high performance supercapacitors.
AB  - Nitrogen-doped mesoporous carbon microfibers (NMCMFs) were prepared via an
      evaporation-induced tri-consistent assembly of a triblock copolymer, resols and
      prehydrolyzed tetraethoxy silane on natural silk followed by pyrolysis. The
      resultant NMCMFs inherit the advantages of both order mesoporous carbons (OMCs)
      and carbon microfibers (CMFs), such as uniform meso-channels, high surface area,
      high nitrogen content, excellent electronic conductivity as well as good
      flexibility. Owing to the well-designed nanostructure and the synergistic effects
      of the strongly coupled components, the binder-free electrodes based on NMCMFs
      exhibit enhanced capacity (189 F g(-1) at 5 mV s(-1)), excellent rate capability
      (107 F g(-1) at 100 mV s(-1)) and durability (maintained over 96% of the initial
      capacitance after 10,000 cycles) in electric double-layer capacitors,
      outperforming those of OMCs and CMFs derived from pristine silk.

PMID- 25588923
TI  - Two-photon imaging with longer wavelength excitation in intact Arabidopsis
      tissues.
AB  - In vivo imaging of living organisms is an important tool to investigate
      biological phenomena. Two-photon excitation microscopy (2PEM) is a laser-scanning
      microscopy that provides noninvasive, deep imaging in living organisms based on
      the principle of multiphoton excitation. However, application of 2PEM to plant
      tissues has not been fully developed, as plant-specific autofluorescence,
      optically dense tissues, and multiple light-scattering structures diminish the
      clarity of imaging. In this study, the advantages of 2PEM were identified for
      deep imaging of living and intact Arabidopsis thaliana tissues. When compared to
      single-photon imaging, near-infrared 2PEM, especially at 1000 nm, reduced
      chloroplast autofluorescence; autofluorescence also decreased in leaves, roots,
      pistils, and pollen grains. For clear and deep imaging, longer excitation
      wavelengths using the orange fluorescent proteins (FPs) TagRFP and tdTomato gave
      better results than with other colors. 2PEM at 980 nm also provided multicolor
      imaging by simultaneous excitation, and the combination of suitable FPs and
      excitation wavelengths allowed deep imaging of intact cells in root tips and
      pistils. Our results demonstrated the importance of choosing both suitable FPs
      and excitation wavelengths for clear two-photon imaging. Further advances in in
      vivo analysis using 2PEM will facilitate more extensive studies in the plant
      biological sciences.

PMID- 25588924
TI  - RBMS3 is a tumor suppressor gene that acts as a favorable prognostic marker in
      lung squamous cell carcinoma.
AB  - Recent research indicates that RBMS3 may act as a tumor suppressor gene (TSG) in
      nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). It
      has been reported that RBMS3 directly binds to the promoter region of c-Myc in
      ESCC and that beta-catenin from both whole cell extracts and nuclear
      fractionation was significantly downregulated in RBMS3-transfected NPC cells
      compared to control cells. The aim of this study was to evaluate the clinical
      significance of the RBMS3 gene expression in relation to the expression of Wnt
      pathway components in patients with lung squamous cell carcinoma (LSCC). RBMS3, c
      Myc and cytoplasmic beta-catenin were detected in 39.76, 56.63 and 89.16 % of 83
      LSCC samples by immunohistochemistry, respectively, in 83 primary LSCC samples.
      Semiquantitative reverse transcriptase-polymerase chain reaction and Western
      blotting demonstrated decreased RBMS3 mRNA and expression in 33.33 % (10/30) and
      36.67 % (11/30) tumor tissues, respectively. Statistical correlation analysis
      showed RBMS3 to be negatively correlated with c-Myc (r = -0.384, p < 0.001) and
      not correlated with cytoplasmic beta-catenin in the LSCC samples. Multivariate
      Cox proportional hazards model analysis showed that the combined marker RBMS3/c
      Myc was an independent prognostic indicator of overall survival (p = 0.001; HR
      3.470; IC 95 %, 1.652-7.290), and c-Myc was a prognostic indicator of disease
      free survival (p < 0.001; HR 3.182; IC 95 %, 1.961-8.920). RBMS3 is a novel TSG
      in LSCC, and its downregulation facilitates development and progression of LSCC.
      Therefore, it is suggested that Rbms3 as a tumor marker may play an important
      role in diagnosis of LSCC. 

PMID- 25588925
TI  - Outcomes of peripheral blood stem cell transplantation patients from HLA
      mismatched unrelated donor with antithymocyte globulin (ATG)-Thymoglobulin versus
      ATG-Fresenius: a single-center study.
AB  - Although antithymocyte globulin (ATG) had been widely used in hematopoietic stem
      cell transplantation from unrelated donor due to its ability to prevent acute and
      chronic graft-versus-host disease (GVHD), the comparative efficacy and safety of
      ATG-Thymoglobulin (ATG-T) and ATG-Fresenius (ATG-F) in patients undergoing HLA
      mismatched allogeneic peripheral blood stem cell transplantation from unrelated
      donors (UR-PBSCT) has not been evaluated. Retrospective analysis of patients who
      underwent HLA-mismatched UR-PBSCT between January 2003 and December 2013 and
      received pre-transplant ATG-T at a total dose of 10 mg/kg or ATG-F at a total
      dose of 20 mg/kg was performed. Patients who received ATG-T (n = 23) or ATG-F (n
      = 28) had similar baseline demographic, disease, and transplant characteristics.
      There were no significant between-groups differences in the probability of acute
      GVHD (P = 0.721) and chronic GVHD (P = 0.439). ATG-F was associated with
      nonsignificant trends toward higher disease-free survival at 3-year follow-up
      compared with ATG-T (45.7 +/- 11.1 vs 61.3 +/- 9.7 %, respectively, P = 0.07). A
      significantly greater proportion of ATG-T patients experienced high fever than
      ATG-F patients (P < 0.01) during ATG infusion. There was no difference in the
      rate of infection between the two treatment groups. There were less adverse
      effects comparing ATG-F with ATG-T. ATG-T at a total dose of 10 mg/kg and ATG-F
      at a total dose of 20 mg/kg had a similar clinical outcome in the setting of HLA
      mismatched UR-PBSCT. 

PMID- 25588926
TI  - Survivorship in untreated breast cancer patients.
AB  - In any disease, the knowledge of the natural history of untreated cases provides
      a real background against which the real advantages of a new treatment itself are
      judged. Fortunately, in the present days, there are scant data on outcomes in
      patients with untreated breast cancer. In an attempt to provide this background
      against which the virtues of current curative and palliative treatments can be
      more accurately assessed, we have reviewed the literature regarding published
      untreated breast cancer series. Taking into consideration all the difficulties of
      analyzing reports written on the last half of the nineteenth century or on the
      first half of the twentieth century, in most reports, patients survived almost 3
      4 years without any type of treatment. Worth mentioning, approximately 5-10 % of
      untreated patients lived longer than 10 years. Thus, the spectrum of clinical
      aggressiveness of untreated breast cancer varies between virulence and chronic
      disease. These facts should be taken into account when considering the value of
      current treatments for early-stage disease. 

PMID- 25588928
TI  - Attentional focus during exposure in spider phobia: the role of schematic versus
      non-schematic imagery.
AB  - Research has provided controversial results regarding the role of distraction
      (vs. attentional focus) during exposure therapy. In the present study, we
      manipulated the nature of the concepts activated during exposure. Sixty-six
      spider phobics were exposed to pictures of spiders and asked, or not, to form
      mental images of concepts that were either related or unrelated to spiders. At
      pre-exposure, mid-exposure, post-exposure, and follow-up, subjective distress,
      heart rate variability, and skin conductance responses were measured and the Fear
      of Spiders Questionnaire and a Behavioural Avoidance Test were performed. Results
      showed that the activation of concepts unrelated to spiders led to return of
      distress at follow-up. Moreover, the activation of concepts related to spiders
      decreased emotional and avoidance responses between sessions. This pattern of
      results suggests that the nature of the activated concepts does not influence
      subjective distress during exposure, but plays an important role in the
      maintenance of distress reduction between sessions. 

PMID- 25588927
TI  - A systematic review and meta-analysis of the association between OGG1 Ser326Cys
      polymorphism and cancers.
AB  - The oxyguanine glycosylase 1 (OGG1) gene has an important role in DNA repair, and
      the polymorphism of the gene may alter cancer susceptibility. This study aims to
      examine the association between the OGG1 Ser326Cys polymorphism and cancer risk
      based on meta-analysis. Relevant studies were identified through a search of
      PubMed and Weipu databases, and a total of 109 studies including 111 comparisons
      containing 34,041 cases and 42,730 controls were enrolled. Overall, significant
      association was observed between OGG1 Ser326Cys polymorphism and cancer risk in
      all genetic models except for heterozygote model (Cys/Cys + Cys/Ser vs Ser/Ser:
      OR 1.071, 95 % CI 1.019-1.125; Cys/Cys vs Cys/Ser + Ser/Ser: OR 1.159, 95 % CI
      1.076-1.248; Cys/Cys vs Ser/Ser: OR 1.202, 95 % CI 1.105-1.308). In stratified
      analysis by cancer type, significantly increased cancer risk was observed in
      digestive system cancer, head and neck cancer and lung cancer. For gynecologic
      cancer, significantly increased cancer risk was also observed in homozygote model
      (OR 1.974, 95 % CI 1.254-3.107). In addition, in stratified analysis by
      ethnicities, increased cancer risk was found in Asians (Cys/Cys vs Cys/Ser +
      Ser/Ser: OR 1.195, 95 % CI 1.088-1.313; Cys/Cys + Cys/Ser vs Ser/Ser: OR 1.115,
      95 % CI 1.045-1.190; Cys/Cys vs Ser/Ser: OR 1.273, 95 % CI 1.149-1.410). The OGG1
      Ser326Cys polymorphism may be a risk factor for cancers of lung, digestive system
      and head and neck. 

PMID- 25588929
TI  - Molecular characteristics of endometrial cancer coexisting with peritoneal
      malignant mesothelioma in Li-Fraumeni-like syndrome.
AB  - BACKGROUND: Endometrial cancer that occurs concurrently with peritoneal malignant
      mesothelioma (PMM) is difficult to diagnose preoperatively. CASE PRESENTATION: A
      postmenopausal woman had endometrial cancer extending to the cervix, vagina and
      pelvic lymph nodes, and PMM in bilateral ovaries, cul-de-sac, and multiple
      peritoneal sites. Adjuvant therapies included chemotherapy and radiotherapy.
      Targeted, massively parallel DNA sequencing and molecular inversion probe
      microarray analysis revealed a germline TP53 mutation compatible with Li-Fraumeni
      like syndrome, somatic mutations of PIK3CA in the endometrial cancer, and a
      somatic mutation of GNA11 and JAK3 in the PMM. Large-scale genomic amplifications
      and some deletions were found in the endometrial cancer. The patient has been
      stable for 24 months after therapy. One of her four children was also found to
      carry the germline TP53 mutation. CONCLUSIONS: Molecular characterization of the
      coexistent tumors not only helps us make the definite diagnosis, but also
      provides information to select targeted therapies if needed in the future.
      Identification of germline TP53 mutation further urged us to monitor future
      development of malignancies in this patient and encourage cancer screening in her
      family.

PMID- 25588930
TI  - Sustained-release methylphenidate in methamphetamine dependence treatment: a
      double-blind and placebo-controlled trial.
AB  - BACKGROUND: The objective of this randomized, double-blind, placebo-controlled
      study was to evaluate the efficacy of sustained-release methylphenidate (MPH-SR)
      in treatment of methamphetamine dependence. METHODS: Fifty-six individuals who
      met DSM-IV-TR criteria for methamphetamine dependence participated in this 10
      week trial. The participants were randomly allocated into two groups and received
      18 to 54 mg/day sustained-released methylphenidate or placebo for 10 weeks.
      Craving was evaluated by a visual analogue craving scale every week. Urinary
      screening test for methamphetamine was carried out each week. The Beck Depression
      Inventory-II (BDI-II) was used to monitor participant depressive symptoms at
      baseline and bi-weekly during the treatment period. RESULTS: At the end of the
      trial, the MPH-SR group was less methamphetamine positive compared to the placebo
      group and the difference was significant (p = 0.03). By the end of the study, MPH
      SR group showed significantly less craving scores compared to the placebo group
      [MD (95% CI) = -10.28(0.88-19.18), t(54) = 2.19, p = 0.03]. There was greater
      improvement in the depressive symptoms scores in the intervention group compared
      to the placebo group [MD (95% CI) =2.03(0.31-3.75), t (54) =2.37, p = 0.02].
      CONCLUSION: Sustained-released methylphenidate was safe and well tolerated among
      active methamphetamine users and significantly reduced methamphetamine use,
      craving and depressive symptoms. TRIAL REGISTRATION: IRCT201202281556N38.

PMID- 25588931
TI  - Subthalamic deep brain stimulation differently alters striatal dopaminergic
      receptor levels in rats.
AB  - High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is recognized
      as an effective treatment for the motor symptoms of Parkinson's disease (PD), but
      its mechanisms, particularly as concern dopaminergic transmission, remain
      unclear. The aim of this study was to evaluate changes in the expression of
      dopaminergic receptors (D1, D2, and D3 receptors) after prolonged (4 h)
      unilateral STN-HFS in anesthetized intact rats and rats with total dopaminergic
      denervation. We used [(3)H]SCH 23390, [(125)I]iodosulpride, and [(125)I]OH-PIPAT
      to assess the densities of D1R, D2R, and D3R, respectively, within different
      areas of the striatum-a major input structure of the basal ganglia-including the
      nucleus accumbens. We found that STN-HFS increased D1 R levels in almost all of
      the striatal areas examined, in both intact and denervated rats. By contrast, STN
      HFS led to a large decrease in D2 R and D3R levels, limited to the nucleus
      accumbens and independent of the dopaminergic state of the animals. These data
      suggest that the influence of STN-HFS on striatal D1 R expression may contribute
      to its therapeutic effects on motor symptoms, whereas its impact on D2R/D3 R
      levels in the nucleus accumbens may account for the neuropsychiatric side effects
      often observed in stimulated PD patients, such as postoperative apathy.

PMID- 25588932
TI  - HealthMpowerment.org: Building Community Through a Mobile-Optimized, Online
      Health Promotion Intervention.
AB  - BACKGROUND: Both young Black men who have sex with men as well as young Black
      transgender women (YBMSM/TW) continue to experience a significant increase in HIV
      incidence. HealthMpowerment.org (HMP) is a mobile phone-optimized, online
      intervention for both YBMSM/TW to build community and facilitate supportive
      relationships. METHODS: To assess the feasibility, acceptability, and preliminary
      outcomes, a 1-month pilot trial of HMP among 15 YBMSM/TW was conducted. RESULTS:
      Retention was 100%. Mean age was 26 years, 60% were HIV-infected, 87% earned
      <$21,000, and 67% were uninsured. Despite the small sample size and limited
      intervention length, statistically significant improvements were seen in social
      support (p = .012), social isolation (p = .050), and depressive symptoms (p =
      .045). CONCLUSION: The HMP pilot trial demonstrated feasibility and
      acceptability. Given the burden of the epidemic among YBMSM/TW, there is an
      imperative to develop, test, and scale up culturally appropriate interventions to
      both prevent HIV acquisition and limit onward transmission.

PMID- 25588933
TI  - Perceptions that influence the maintenance of scientific integrity in community
      based participatory research.
AB  - Scientific integrity is necessary for strong science; yet many variables can
      influence scientific integrity. In traditional research, some common threats are
      the pressure to publish, competition for funds, and career advancement. Community
      based participatory research (CBPR) provides a different context for scientific
      integrity with additional and unique concerns. Understanding the perceptions that
      promote or discourage scientific integrity in CBPR as identified by professional
      and community investigators is essential to promoting the value of CBPR. This
      analysis explores the perceptions that facilitate scientific integrity in CBPR as
      well as the barriers among a sample of 74 professional and community CBPR
      investigators from 25 CBPR projects in nine states in the southeastern United
      States in 2012. There were variations in perceptions associated with team member
      identity as professional or community investigators. Perceptions identified to
      promote and discourage scientific integrity in CBPR by professional and community
      investigators were external pressures, community participation, funding, quality
      control and supervision, communication, training, and character and trust. Some
      perceptions such as communication and training promoted scientific integrity
      whereas other perceptions, such as a lack of funds and lack of trust could
      discourage scientific integrity. These results demonstrate that one of the most
      important perceptions in maintaining scientific integrity in CBPR is active
      community participation, which enables a co-responsibility by scientists and
      community members to provide oversight for scientific integrity. Credible CBPR
      science is crucial to empower the vulnerable communities to be heard by those in
      positions of power and policy making. 

PMID- 25588935
TI  - Impact of Fruit Smoothies on Adolescent Fruit Consumption at School.
AB  - We examine the impact of serving fruit smoothies during school breakfast on fruit
      consumption among middle school and high school students. We draw on
      observational plate-waste data over a 10-week period during which fruit smoothies
      were introduced for breakfast at two Utah schools. Our total sample includes
      2,760 student-day observations. We find that the fraction of students eating a
      full serving of whole fruit increased from 4.3% to 45.1%. As such, school
      districts should consider offering fruit smoothies as part of a set of
      interventions designed to increase fruit consumption at school. 

PMID- 25588934
TI  - The U.S. National Tips From Former Smokers Antismoking Campaign: Promoting
      Awareness of Smoking-Related Risks, Cessation Resources, and Cessation Behaviors.
AB  - OBJECTIVE: Evaluate the second flight of the U.S. Tips From Former Smokers (Tips)
      campaign. METHOD: Data were analyzed from an online consumer panel of U.S. adult
      smokers before (n = 1,404) and after (n = 1,401) the 2013 Tips campaign launch.
      Generalized estimating equation models assessed whether the Tips advertisement
      recall was associated with knowledge about smoking-related risks in the Tips
      advertisements, awareness and use of a toll-free quitline and cessation websites,
      and quit attempts. RESULTS: Seventy-one percent of participants at Wave 2
      reported that they recalled seeing at least one Tips advertisement. Smokers who
      recalled seeing a Tips advertisement were more likely to (a) show increases over
      baseline in knowledge of health risks such as amputation: 65% versus 34%, p <
      .001; blindness: 27% versus 12%, p < .001; and (b) to be aware of a quitline (41%
      vs. 30%, p < .001) and cessation website (28% vs. 20%, p < .001). Recall of Tips
      advertisements was also associated with greater likelihood of reporting having
      visited cessation websites (odds ratio [OR] = 1.62, 95% confidence interval [CI]
      = 1.27-2.06), having called a quitline (OR = 2.28, 95% CI = 1.61-3.24), and
      having made a quit attempt (OR = 1.18, 95% CI = 1.00-1.39), although these
      results were only statistically significant in the unadjusted models.
      CONCLUSIONS: The 2013 Tips campaign was successful in increasing knowledge of
      health risks and awareness of tobacco cessation resources.

PMID- 25588936
TI  - Early Success Is Vital in Minimal Worksite Wellness Interventions at Small
      Worksites.
AB  - INTERVENTION: In an effort to increase physical activity, 15 workplaces
      participated in a minimal-contact 10,000-steps-a-day program sponsored by the
      Sedgwick County Health Department in 2007 and 2008. Pedometers were provided to
      measure participants' weekly steps for the 10-week intervention. METHOD:
      Participants were defined as those who completed the preregistration survey and
      logged at least 1 week of results. Registrants were defined as those who
      completed a registration survey but did not log any weekly results. The primary
      dependent variable was whether or not participants achieved weekly success, as
      measured by achieving at least 70,000 steps in a week. A secondary dependent
      variable was participants' number of steps each week during the weeks they logged
      results. Repeated measures logistic regression analysis was conducted to identify
      factors associated with weekly success. RESULTS: Of the 2,515 registrants, 1,292
      (51%) were participants. The average number of weeks of participation for this 10
      week intervention was 5.6 weeks (SD = 3.4). Those from small employers (n < 750)
      were more likely (OR = 2.0) than those from large organizations (n > 750) to
      become participants. Participants who achieved at least 70,000 steps in the first
      week of the intervention were 7.3 times more likely than participants who walked
      less than 70,000 steps in the first week to achieve 70,000 steps each week for
      all 10 weeks. CONCLUSIONS: Results from implementing a minimal-contact 10,000
      step intervention can be maximized by targeting small worksites and supporting
      employees to achieve 70,000 steps in their first week.

PMID- 25588937
TI  - Physical and Social-Motivational Contextual Correlates of Youth Physical Activity
      in Underresourced Afterschool Programs.
AB  - Afterschool programs (ASPs) have become increasingly recognized as a key context
      to support youth daily physical activity (PA) accrual. The purpose of the present
      study was to assess the physical and social-motivational climate characteristics
      of ASPs associated with youth PA, and variations in contextual correlates of PA
      by youth sex. Systematic observations of 7 ASPs serving underserved youth
      (minority, low income) was conducted using the System for Observing Play and
      Leisure Activity in Youth and a social-motivational climate observation tool
      founded on self-determination theory. For five program days at each site, teams
      of two coders conducted continuous observations of youth PA (sedentary, moderate,
      vigorous), five physical features (e.g., equipment availability), eight staff
      interactions (e.g., encourage PA), and seven motivational climate components
      (e.g., inclusive). Aligned with previous research, regressions controlling for
      variations by site indicated that organized PA, provision of portable equipment,
      and staff PA participation and supervision are key correlates of youth PA.
      Moreover, as the first study to systematically observe motivational-context
      characteristics of ASPs, we identified several key modifiable motivational
      features that are necessary to address in order to increase youth engagement in
      PA during the out-of-school hours. Among motivational features assessed,
      "relatedness" components (positive peer relations, inclusive/cooperative
      activities) were primary correlates of girls' PA. In contrast, all three
      motivational features specified by self-determination theory (support for
      autonomy, mastery/competence, and inclusion/relatedness) were correlated with
      boys' PA. Findings are discussed in terms of policy and practice for
      understanding strengths and needs of ASPs to effectively engage youth in PA. 

PMID- 25588939
TI  - An iron-catalyzed cascade approach to benzo[b]carbazole synthesis followed by 1,4
      sulfonyl migration.
AB  - A simple and straightforward approach was developed to construct 5H
      benzo[b]carbazole derivatives by iron catalysis in a cascade sequence. The
      notable features of this work include an atom-economical cascade sequence,
      unprecedented 1,4-sulfonyl migration, tolerance of a variety of functional
      groups, good yields, and an economical catalytic system. 

PMID- 25588938
TI  - Intermediate Catheters Reduce the Length of Mechanical Thrombectomy Procedures in
      Acute Basilar Artery Occlusions.
AB  - BACKGROUND AND PURPOSE: In the past years, technical developments have raised
      recanalization rates of endovascular treatments of intracerebral artery
      occlusions in acute ischemic stroke. By using stent retrievers, several
      prospective trials have reported recanalization rates up to 79 % as well as good
      neurological outcome in up to 58 % of the cases. The degree of the recanalization
      and the length of the procedure are factors known to influence the clinical
      outcome of patients treated endovascularly. Yet, still little is known about
      factors influencing the angiographic results of thrombectomy procedures. The
      purpose of this study was to investigate whether the use of intermediate
      catheters affects the angiographic results of thrombectomy procedures in basilar
      artery occlusions. MATERIALS AND METHODS: A total of 47 consecutive patients with
      acute basilar artery occlusions who underwent endovascular treatment with stent
      retrievers in our department were retrospectively identified. We analyzed the
      angiographic data regarding the use of intermediate catheters, the lengths of the
      procedures, the number of passes of the stent retrievers, the angiographic
      results, and the site of access to the basilar artery. RESULTS: Recanalization
      with modified thrombolysis in cerebral infarction (mTICI) >= 2b was achieved in
      74.5 %. Intermediate catheters were used in 13 cases. The mean length of the
      procedures was significantly shorter when intermediate catheters were used (44.8
      +/- 27.6 vs. 70.7 +/- 41.4 min, P = .043). There were no significant differences
      in the number of passes or in the final mTICI scores. CONCLUSIONS: The use of
      intermediate catheters significantly reduces the length of mechanical
      thrombectomy procedures in acute basilar artery occlusions.

PMID- 25588941
TI  - Effect of alternate-day fasting therapy combined with Linggui Zhugan Decoction ()
      on hepatic oxidative stress in hyperlipidemic rat.
AB  - OBJECTIVE: To observe the effect of alternate-day fasting (ADF) therapy combined
      with Linggui Zhugan Decoction (, LZD) on hepatic oxidative stress and blood
      lipids in hyperlipidemic rats. METHODS: Fifty-two Wistar rats were randomly
      assigned to two groups: the high-fat-diet (HF) group and the normal-diet (ND)
      group. Hyperlipidemia was induced by feeding rats with high-cholesterol-diet for
      5 weeks. Then the HF group was randomized to the model-control (MC) group, the
      alternate-day-fasting (ADF) group, and the ADF combined with LZD (AL) group. The
      ND group was regarded as the negative control (NC) group. The AL and ADF groups
      were put on fast for 24 h on alternate days for 4 weeks. The AL group was
      administrated with LZD on the fast days. Body weight and food intake were
      measured once a week. After 4-week ADF, blood sample was collected for
      determination of plasma total cholesterol (TC), triglyceride (TG), low-density
      lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C).
      Liver oxidative stress parameters including total superoxide dismutase (T-SOD)
      activity, malondialdehyde (MDA) level and glutathione (GSH) content were also
      tested. RESULTS: Body weight in the HF group decreased significantly (P<0.01).
      TC, TG, HDL-C, and LDL-C concentrations in the HF group were higher than those in
      the NC group (P<0.01), respectively. T-SOD in the HF group was clearly lower than
      that in the NC group (P<0.05). After 4-week intervention, body weight, TC and TG
      concentrations in the ADF and AL groups declined significantly, respectively,
      compared to MC group (P<0.05). GSH in the ADF and AL groups were much higher than
      those in the MC group (P<0.01). MDA level was also greatly higher in the ADF
      group as compared with the NC group (P<0.05). CONCLUSION: ADF therapy combined
      with LZD may be used as an effective combination approach for treatment of
      hyperlipidemia and oxidative stress damage.

PMID- 25588940
TI  - Protective effect of propyl gallate against oxidized low-density lipoprotein
      induced injury of endothelial cells.
AB  - OBJECTIVE: To evaluate the protective effect of propyl gallate (PG), an alkyl
      ester of gallic acid which is an active ingredient of Radix Paeoniae, against
      oxidized low-density lipoprotein (ox-LDL)-induced apoptosis and death in
      endothelial cells (ECs) and to find out its preliminary mechanism. METHODS: The
      cultured endothelial cells were divided into normal, model (ox-LDL), control
      (fetal bovine serum), PG high dose (20 MUg/mL), PG middle dose (10 MUg/mL), and
      PG low dose (5 MUg/mL) groups, each derived from three different pools of
      umbilical cords. The model of injured human umbilical vein endothelial cells
      (HUVECs) was induced by ox-LDL. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H
      tetrazolium bromide (MTT) assay, Hoechst 33258 staining, flow cytometry and
      measurement of nitrogen monoxidum (NO) release were used to evaluate the
      protective effect of PG against ox-LDL-induced apoptosis and death in HUVECs. To
      find out the mechanism of this protective effect, the expression of endothelial
      nitric oxide synthase (eNOS) mRNA, eNOS protein expression, immunofluorescence of
      intracellular reactive oxygen species (ROS) and activities of malondialdehyde
      (MDA), superoxidedismutase (SOD) and glutathione peroxidase (GPx) were observed.
      RESULTS: PG significantly reduced ox-LDL-induced apoptosis and cell death. The
      percentage of cells death and apoptosis was significantly higher in the ox-LDL
      group than that in the control group (P<0.05). Compared with the control group,
      the cells death and apoptosis of PG group was no different (P>0.05). As compared
      with the ox-LDL group, results of the PG high dose group showed that cell
      viability was significantly increased (P<0.05), the level of NO release,
      expression of eNOS mRNA, densitometric value of eNOS protein expression, as well
      as the activities of SOD and GPx were all significantly higher (all P<0.05).
      CONCLUSION: PG could potentially serve as a novel endothelial protective agent
      against ox-LDL-induced injury of endothelial cell.

PMID- 25588942
TI  - Cytotoxicity of syringin and 4-methoxycinnamyl alcohol isolated from Foeniculum
      vulgare on selected human cell lines.
AB  - This study was carried out to determine the cytotoxic effect of seven plant
      extracts and the isolated compounds - syringin and 4-methoxycinnamyl alcohol - on
      cancerous and non-cancerous cells. The ethanol extract of Foeniculum vulgare was
      found to exhibit the most significant toxicity with an IC50 value of 19.97 MUg/mL
      on HeLa cells. Bioassay-guided fractionation led to the isolation of two
      compounds, syringin (1) and 4-methoxycinnamyl alcohol (2). Both compounds showed
      toxicity against MCF-7, HeLa and DU145 cancer cell line. The results showed that
      compound 2 showed high toxicity against all the cancer cell lines with IC50
      values of 14.24, 7.82 and 22.10 MUg/mL, respectively. 4-Methoxycinnamyl alcohol
      also showed no apoptotic effect in cell cycle analysis after 48 h at a
      concentration of 10 MUg/mL. However, DNA fragmentation study revealed that
      necrosis took place at a concentration of 10 MUg/mL after 48 h exposure.

PMID- 25588943
TI  - Canine atopic dermatitis diagnostic criteria: evaluation of four sets of
      published criteria among veterinary students.
AB  - Canine atopic dermatitis (cAD) is a major teaching point as its diagnosis and
      treatment are difficult. During 11 weeks, 140 dogs and students (third, fourth,
      and fifth years) were recruited and paired. One of the four lists of diagnostic
      criteria was randomly attributed to each student. Concordance results, calculated
      with Cohen's kappa, ranged from slight (kappa=0.07) to moderate (kappa=0.53).
      Favrot's diagnostic criteria received the best results. It has been observed that
      results are improved with clinical experience. We observed that students often
      forgot that Favrot's criteria apply only to pruritic dogs and that the
      fulfillment of the criteria allows only a suspicion, not a diagnosis, of cAD.
      Primary pruritus and corticosteroid-responsive pruritus were often misunderstood.

PMID- 25588944
TI  - A Tetrahymena Hsp90 co-chaperone promotes siRNA loading by ATP-dependent and ATP
      independent mechanisms.
AB  - The loading of small interfering RNAs (siRNAs) and microRNAs into Argonaute
      proteins is enhanced by Hsp90 and ATP in diverse eukaryotes. However, whether
      this loading also occurs independently of Hsp90 and ATP remains unclear. We show
      that the Tetrahymena Hsp90 co-chaperone Coi12p promotes siRNA loading into the
      Argonaute protein Twi1p in both ATP-dependent and ATP-independent manners in
      vitro. The ATP-dependent activity requires Hsp90 and the tetratricopeptide repeat
      (TPR) domain of Coi12p, whereas these factors are dispensable for the ATP
      independent activity. Both activities facilitate siRNA loading by counteracting
      the Twi1p-binding protein Giw1p, which is important to specifically sort the 26-
      to 32-nt siRNAs to Twi1p. Although Coi12p lacking its TPR domain does not bind to
      Hsp90, it can partially restore the siRNA loading and DNA elimination defects of
      COI12 knockout cells, suggesting that Hsp90- and ATP-independent loading of siRNA
      occurs in vivo and plays a physiological role in Tetrahymena. 

PMID- 25588946
TI  - Isolation and characterization of an antimicrobial lipopeptide produced by
      Paenibacillus ehimensis MA2012.
AB  - In this study, a novel lipopeptide antibiotic was isolated from the culture
      supernatant of Paenibacillus ehimensis strain MA2012. After analyses by mass
      spectrometry (MS), nuclear magnetic resonance (NMR), and high resolution mass
      spectrometry (HR-MS/MS) the compound was identified to be polypeptin C consisting
      of 3-hydroxy-4-methyl-hexanoic acid moiety and nine amino acids as peptide body.
      It has the same molecular mass (1115 Da) with that of polypeptin A and B but the
      amino acid positions differ. A relatively low concentration (125 ppm) of
      polypeptin C lowered the surface tension of water from 72.2 to 36.4 mN/m. It
      showed antimicrobial activity against several plant pathogenic bacteria and
      fungi. When the polypeptin C was applied to the ripe pepper fruits previously
      inoculated with conidia of Colletotrichum gloeosporioides, the hyphal growth on
      the fruit was significantly suppressed. Moreover, the hyphal morphology of C.
      gloeosporioides was greatly affected by the purified compound. All these data
      suggest the great potential of P. ehimensis MA2012 to control plant fungal and
      bacterial diseases.

PMID- 25588947
TI  - A murine model of lung ischemia and reperfusion injury: tricks of the trade.
AB  - BACKGROUND: Pulmonary ischemia-reperfusion injury (IRI) causes postoperative
      morbidity in patients undergoing lung transplantation, isolated lung perfusion,
      and cardiopulmonary bypass and may lead to potentially lethal pathologies such as
      respiratory shock. In-depth study of this pathology requires a reliable animal
      model. Mice are a popular species to develop experimental models because of their
      logistic advantages and the availability of knock outs. However, their small size
      warrants microsurgical techniques and a skilled surgeon. MATERIALS AND METHODS:
      We developed a murine model of pulmonary anoxic IRI through hilar clamping using
      adult female Swiss mice. After left thoracotomy, we expose the pulmonary hilum
      keeping the ribs and the muscles of back and forepaw intact. A microvascular
      clamp is placed over the entire hilum, occluding bronchus, pulmonary artery, and
      vein. RESULTS: Our model proved to be simple, reliable, and reproducible, showing
      minimal preoperative and postoperative mortality. Histopathologic analysis
      indicated all characteristic features of pulmonary IRI, such as an early
      recruitment of lymphocytes followed by neutrophil influx. CONCLUSIONS: This
      article presents a murine surgery model for pulmonary IRI based on a muscle
      sparing thoracotomy. The minimal approach limits manipulation of lung tissue,
      minimizing mortality and non-IRI-induced injury.

PMID- 25588945
TI  - LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal
      sorting, and degradation.
AB  - Lysosomal degradation is essential for the termination of EGF-stimulated EGF
      receptor (EGFR) signaling. This requires EGFR sorting to the intraluminal
      vesicles (ILVs) of multi-vesicular endosomes (MVEs). Cytosolic proteins including
      the ESCRT machineries are key regulators of EGFR intraluminal sorting, but roles
      for endosomal transmembrane proteins in receptor sorting are poorly defined.
      Here, we show that LAPTM4B, an endosomal transmembrane oncoprotein, inhibits EGF
      induced EGFR intraluminal sorting and lysosomal degradation, leading to enhanced
      and prolonged EGFR signaling. LAPTM4B blocks EGFR sorting by promoting
      ubiquitination of Hrs (an ESCRT-0 subunit), which inhibits the Hrs association
      with ubiquitinated EGFR. This is counteracted by the endosomal PIP kinase,
      PIPKIgammai5, which directly binds LAPTM4B and neutralizes the inhibitory
      function of LAPTM4B in EGFR sorting by generating PtdIns(4,5)P2 and recruiting
      SNX5. PtdIns(4,5)P2 and SNX5 function together to protect Hrs from
      ubiquitination, thereby promoting EGFR intraluminal sorting. These results reveal
      an essential layer of EGFR trafficking regulated by LAPTM4B, PtdIns(4,5)P2
      signaling, and the ESCRT complex and define a mechanism by which the oncoprotein
      LAPTM4B can transform cells and promote tumor progression. 

PMID- 25588948
TI  - Celecoxib inhibits early cutaneous wound healing.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) is an inducible enzyme that is rapidly
      upregulated in response to injury, resulting in the production of prostaglandin
      E2 (PGE2), a primary mediator of inflammation and wound healing. The selective
      COX-2 inhibitor, celecoxib, is was used to treat pain and inflammation. When used
      to treat injuries, we postulated that loss of PGE2 activity by COX-2 inhibition
      would have detrimental effects on wound healing. Our objective was to study the
      effect of selective COX-2 inhibition with celecoxib on cutaneous wound healing.
      MATERIALS AND METHODS: C57BL/6J mice with uniform full-thickness wounds (1 cm(2))
      to their dorsum were fed diet with or without celecoxib (1500 ppm). Wound closure
      analysis measured wound contraction, reepithelialization, and open wound as a
      percentage of the initial wound area, and was quantified by planimetry. Wounds
      were excised en bloc at day 7 to examine cellular proliferation, angiogenesis,
      cytokine production, and extracellular matrix (ECM) formation. RESULTS: Celecoxib
      induced reduction in wound PGE2 levels was documented by enzyme-linked
      immunosorbent assay on day 7 after wounding. Wound contraction and
      reepithelialization were significantly reduced by celecoxib treatment, resulting
      in a 20% greater open wound area at day 7 (P < 0.05). In response to celecoxib
      treatment, immunohistochemistry analysis showed epithelial cell proliferation,
      angiogenesis, and ECM components including collagen and myofibroblasts were
      significantly decreased. CONCLUSIONS: Wound healing is significantly delayed by
      celecoxib treatment. These data indicate that COX-2 and its downstream product
      PGE2 modulate the activity of multiple essential functions of the inflammatory
      stroma, including epithelial proliferation, angiogenesis, and ECM production. As
      a result, reepithelialization and wound closure are delayed by celecoxib
      treatment. These findings have potential clinical implications in postoperative
      wound management.

PMID- 25588949
TI  - Hydrogen-rich saline attenuates ischemia-reperfusion injury in skeletal muscle.
AB  - BACKGROUND: To investigate the potential beneficial effect of hydrogen-rich
      saline (HRS) in ischemia-reperfusion (IR) injury of skeletal muscle. METHODS:
      Three experimental groups were established in male Sprague-Dawley rats: (1) sham
      group, (2) IR with normal saline group, (3) and IR with HRS group. A rat model of
      skeletal muscle IR injury was induced by 3-h tourniquet occlusion on its left
      hind limb and 4-h reperfusion. Normal saline and HRS (1.0 mL/100 g) were
      administered intraperitoneally at 10 min before reperfusion, respectively. Muscle
      and serum samples were analyzed for detecting the levels of myeloperoxidase
      (MPO), superoxide dismutase (SOD), malondialdehyde (MDA), and hydroxyl radical
      (*OH). Muscle samples were assessed by wet/dry rate, hematoxylin and eosin
      histologic assessment, Bcl2, Bax, cytochrome C, LC3B, terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling, and electron microscopy.
      RESULTS: The wet/dry ratio increased significantly in the IR group (P < 0.01
      compared with that in the sham group) and decreased significantly in IR with HRS
      groups (4.12 +/- 0.14 versus 4.12 +/- 0.14, P < 0.01 compared with that in the IR
      group). Muscle tissues and serum of the IR group had significantly increased
      levels of MPO, MDA, *OH content, and decreased SOD activities compared with the
      sham group (P < 0.01). The activity of SOD in the IR with HRS group was greatly
      elevated compared with that in the IR group (295.028 +/- 9.288 versus 249.190 +/-
      5.450 in muscle tissues; 91.627 +/- 2.604 versus 73.4045 +/- 6.487 in serum; P <
      0.01), whereas the levels of MPO, MDA, and *OH content were clearly reduced (MPO:
      0.5649 +/- 0.0724 versus 1.0984 +/- 0.0824 in muscle tissues; 0.7257 +/- 0.1232
      versus 1.3147 +/- 0.0531 in serum. MDA: 4.457 +/- 0.650 versus 7.107 +/- 0.597 in
      muscle tissues; 2.531 +/- 0.434 versus 4.626 +/- 0.237 in serum. *OH: 16.451 +/-
      0.806 versus 19.871 +/- 0.594 in muscle tissues; 500.212 +/- 7.387 versus 621.352
      +/- 7.591 in serum, P < 0.01). The integrated optical density of positive
      amethyst staining increased significantly in the IR group (P < 0.01 compared with
      that in the sham group) and decreased significantly in IR with HRS group (928.79
      +/- 234.537 versus 3005.972 +/- 83.567, P < 0.01 compared with that in the IR
      group). Muscle tissues of the IR group had significantly increased levels of Bax,
      cytochrome C, LC3B content, and decreased Bcl2 activities compared with those in
      the sham group (P < 0.01). The activity of Bcl2 in the IR with HRS group was
      greatly elevated compared with that in the IR group (0.2635 +/- 0.0704 versus
      0.1242 +/- 0.0662; P < 0.01), whereas the levels of Bax, cytochrome C, and LC3B
      content were clearly reduced (Bax: 0.3103 +/- 0.0506 versus 0.5122 +/- 0.0148;
      cytochrome C: 0.4194 +/- 0.1116 versus 0.8127 +/- 0.0166; LC3B: 0.5884 +/- 0.0604
      versus 1.3758 +/- 0.0319; respectively, P < 0.01). CONCLUSIONS: HRS seems to be
      effective in attenuating IR injury in skeletal muscle via its antioxidant, anti
      apoptosis, and anti-autophagy effect.

PMID- 25588951
TI  - Sexual health is another commissioning crisis.

PMID- 25588950
TI  - Increasing diversity of the biomedical workforce through community engagement:
      The University of Utah Native American Summer Research Internship.

PMID- 25588952
TI  - Magnetic nanoparticles: general discussion.

PMID- 25588953
TI  - Rhodium nanoparticle-mesoporous silicon nanowire nanohybrids for hydrogen
      peroxide detection with high selectivity.
AB  - Developing nanostructured electrocatalysts, with low overpotential, high
      selectivity and activity has fundamental and technical importance in many fields.
      We report here rhodium nanoparticle and mesoporous silicon nanowire (RhNP@mSiNW)
      hybrids for hydrogen peroxide (H2O2) detection with high electrocatalytic
      activity and selectivity. By employing electrodes that loaded with RhNP@mSiNW
      nanohybrids, interference caused from both many electroactive substances and
      dissolved oxygen were eliminated by electrochemical assaying at an optimal
      potential of +75 mV. Furthermore, the electrodes exhibited a high detection
      sensitivity of 0.53 MUA/mM and fast response (< 5 s). This high-performance
      nanohybrid electrocatalyst has great potential for future practical application
      in various oxidase-base biosensors.

PMID- 25588954
TI  - Effective half-lives of 137Cs in giant butterbur and field horsetail, and the
      distribution differences of potassium and 137Cs in aboveground tissue parts.
AB  - Concentrations of (137)Cs and (40)K in different tissues of edible wild
      herbaceous plants, that is, leaf blade and petiole for giant butterbur (Petasites
      japonicas (Siebold et Zucc.) Maxim.), and leaf, stem and strobilus for fertile
      shoot of field horsetail (Equisetum arvense L.) were measured in 2012-2014 to
      clarify the effect in Japan from the Fukushima Daiichi Nuclear Power Plant
      accident. The concentrations of (137)Cs decreased with time with effective half
      lives of ca. 450 d and 360 d for giant butterbur and field horsetail,
      respectively. The ANOVA test revealed that (40)K and (137)Cs distributions in
      leaf blade and petiole for giant butterbur and leaf and stem for field horsetail
      were different. Therefore, other plants, leaf and stem for Japanese knotweed
      (Fallopia japonica (Houtt.) Ronse Decr.) and Canada goldenrod (Solidago
      canadensis L.), and leaf blade and petiole for gingko (Ginkgo biloba L.) and
      Someiyoshino cherry (Cerasus * yedoensis (Matsum.) A.V.Vassil. 'Somei-yoshino')
      were collected from the same sampling field and their (137)Cs and (40)K
      concentrations were compared to those in the giant butterbur and field horsetail
      parts. For (137)Cs, concentrations in leaf blade and leaf parts were 1.1-6.0
      times higher than those in petiole and stem parts for all six plants. On the
      other hand, (40)K concentrations in leaf blade and leaf parts were 0.40-0.97 of
      those observed in petiole and stem parts. Discrimination ratios of (40)K/(137)Cs
      of leaf blade to petiole or leaf to stem were then calculated and they ranged
      from 0.09 to 0.57. These results suggested that Cs and K did not behave similarly
      in these plants. Thus, to understand the radiocesium fate in plants, K
      measurement results should not be used as an analog for Cs behavior although Cs
      is known to have a similar chemical reactivity to that of K.

PMID- 25588955
TI  - The role of endoplasmic reticulum-related BiP/GRP78 in interferon gamma-induced
      persistent Chlamydia pneumoniae infection.
AB  - Direct interaction of Chlamydiae with the endoplasmic reticulum (ER) is essential
      in intracellular productive infection. However, little is known about the
      interplay between Chlamydiae and the ER under cellular stress conditions that are
      observed in interferon gamma (IFN-gamma) induced chlamydial persistent infection.
      ER stress responses are centrally regulated by the unfolded protein response
      (UPR) under the control of the ER chaperone BiP/GRP78 to maintain cellular
      homeostasis. In this study, we could show that the ER directly contacted with
      productive and IFN-gamma-induced persistent inclusions of Chlamydia pneumoniae
      (Cpn). BiP/GRP78 induction was observed in the early phase but not in the late
      phase of IFN-gamma-induced persistent infection. Enhanced BiP/GRP78 expression in
      the early phase of IFN-gamma-induced persistent Cpn infection was accompanied by
      phosphorylation of the eukaryotic initiation factor-2alpha (eIF2alpha) and down
      regulation of the vesicle-associated membrane protein-associated protein B. Loss
      of BiP/GRP78 function resulted in enhanced phosphorylation of eIF2alpha and
      increased host cell apoptosis. In contrast, enhanced BiP/GRP78 expression in IFN
      gamma-induced persistent Cpn infection attenuated phosphorylation of eIF2alpha
      upon an exogenous ER stress inducer. In conclusion, ER-related BiP/GRP78 plays a
      key role to restore cells from stress conditions that are observed in the early
      phase of IFN-gamma-induced persistent infection. 

PMID- 25588956
TI  - Erratum to: The lipidome of the photosynthetic bacterium Rhodobacter sphaeroides
      R26 is affected by cobalt and chromate ions stress.

PMID- 25588958
TI  - Rapid, sensitive, and reusable detection of glucose by a robust radiofrequency
      integrated passive device biosensor chip.
AB  - Tremendous demands for sensitive and reliable label-free biosensors have
      stimulated intensive research into developing miniaturized radiofrequency
      resonators for a wide range of biomedical applications. Here, we report the
      development of a robust, reusable radiofrequency resonator based integrated
      passive device biosensor chip fabricated on a gallium arsenide substrate for the
      detection of glucose in water-glucose solutions and sera. As a result of the
      highly concentrated electromagnetic energy between the two divisions of an
      intertwined spiral inductor coupled with an interdigital capacitor, the proposed
      glucose biosensor chip exhibits linear detection ranges with high sensitivity at
      center frequency. This biosensor, which has a sensitivity of up to 199 MHz/mgmL(
      1) and a short response time of less than 2 sec, exhibited an ultralow detection
      limit of 0.033 MUM and a reproducibility of 0.61% relative standard deviation. In
      addition, the quantities derived from the measured S-parameters, such as the
      propagation constant (gamma), impedance (Z), resistance (R), inductance (L),
      conductance (G) and capacitance (C), enabled the effective multi-dimensional
      detection of glucose.

PMID- 25588957
TI  - The Photosystem II D1-K238E mutation enhances electrical current production using
      cyanobacterial thylakoid membranes in a bio-photoelectrochemical cell.
AB  - The conversion of solar energy (SEC) to storable chemical energy by
      photosynthesis has been performed by photosynthetic organisms, including oxygenic
      cyanobacteria for over 3 billion years. We have previously shown that crude
      thylakoid membranes from the cyanobacterium Synechocytis sp. PCC 6803 can reduce
      the electron transfer (ET) protein cytochrome c even in the presence of the PSII
      inhibitor DCMU. Mutation of lysine 238 of the Photosystem II D1 protein to
      glutamic acid increased the cytochrome reduction rates, indicating the possible
      position of this unknown ET pathway. In this contribution, we show that D1-K238E
      is rather unique, as other mutations to K238, or to other residues in the same
      vicinity, are not as successful in cytochrome c reduction. This observation
      indicates the sensitivity of ET reactions to minor changes. As the next step in
      obtaining useful SEC from biological material, we describe the use of crude
      Synechocystis membranes in a bio-photovoltaic cell containing an N-acetyl
      cysteine-modified gold electrode. We show the production of significant current
      for prolonged time durations, in the presence of DCMU. Surprisingly, the presence
      of cytochrome c was not found to be necessary for ET to the bio-voltaic cell. 

PMID- 25588959
TI  - Prospective evaluation of early postoperative male and female sexual function
      after radical prostatectomy with erectile nerves preservation.
AB  - Prostate cancer screening has led to the diagnosis of localized prostate cancer
      in increasingly young and sexually active men. Accordingly, the impact of cancer
      treatment on sexual function is gaining more attention. To prospectively evaluate
      the impact of radical prostatectomy (RP) on male, female and conjugal sexual
      function. Patients were prospectively assessed by an urologist and a sexologist
      before and 6 months after robot-assisted laparoscopic RP (RALP). RALP was
      performed with uni- or bilateral neurovascular bundle preservation by a single
      surgeon. Postoperatively, all patients were prescribed tadalafil 20 mg, 3 times a
      week during 6 months. Male and female sexual functions were evaluated by using
      the International Index of Erectile Function (IIEF-5), the Female Sexual Function
      Index (FSFI) and the Lock-Wallace Marital Adjustment Test (MAT). Continuous
      variables were analyzed with rank-sum and t-tests, as needed, and categorical
      variables with chi-squared tests. All tests were two-sided, with a P-value ? 0.05
      considered significant. Twenty-one couples were included. Mean patient male and
      female age was 62.4 and 60.7 years, respectively. Bilateral nerve sparing was
      performed in 12/21 (57%) patients. Median preoperative IIEF-5 was 20/25,
      corresponding to mild erectile dysfunction (ED). Median preoperative FSFI and MAT
      were both within normal range (28/36 and 114/158, respectively). Six months
      following surgery, both IIEF-5 (11/25) and FSFI (25/36) had significantly dropped
      (P=0.007 and 0.003, respectively). Postoperative decreases in IIEF-5 and FSFI
      scores were associated within couples. MAT scores (115/158), however, remained
      unaffected by RALP, showing an unmodified relationship satisfaction
      postoperatively. Finally, bilateral nerve sparing surgery preserved not only male
      but also female sexual function. This study shows that the expected short-term
      post-RALP ED is associated with a worsening of female sexual function, whereas
      nerve sparing surgery has a protective effect on both the patient's and his
      partner's sexual function with a significant effect of bilateral over unilateral
      neurovascular bundle preservation. Furthermore, we found that conjugal complicity
      remains stable throughout the first semestrial postoperative period despite the
      decrease in sexual function.

PMID- 25588960
TI  - Molecular recognition in protein modification with rhodium metallopeptides.
AB  - Chemical manipulation of natural, unengineered proteins is a daunting challenge
      which tests the limits of reaction design. By combining transition-metal or other
      catalysts with molecular recognition ideas, it is possible to achieve site
      selective protein reactivity without the need for engineered recognition
      sequences or reactive sites. Some recent examples in this area have used
      ruthenium photocatalysis, pyridine organocatalysis, and rhodium(II)
      metallocarbene catalysis, indicating that the fundamental ideas provide
      opportunities for using diverse reactivity on complex protein substrates and in
      complex cell-like environments. 

PMID- 25588961
TI  - Bio-inspired mechanistic insights into CO2 reduction.
AB  - The global energy and environmental concerns related to the excess CO2
      concentration in the atmosphere have intensified the research and development
      regarding CO2 utilization. Due to the high stability and inertness of CO2, CO2
      functionalization under mild conditions has been proven to be extremely
      challenging. Nature has, however, evolved efficient pathways to achieve this
      difficult transformation. Herein, we compare the mechanisms of CO2 two-electron
      reduction followed by synthetic catalysts and those by carbon monoxide
      dehydrogenase and formate dehydrogenase in order to provide more mechanistic
      insights into future catalyst design. 

PMID- 25588962
TI  - Pre- to postsleep change in psychophysiological reactivity to emotional films:
      Late-night REM sleep is associated with attenuated emotional processing.
AB  - Rapid eye movement (REM) sleep has been postulated to facilitate emotional
      processing of negative stimuli. However, empirical evidence is mixed and
      primarily based on self-report data and picture-viewing studies. This study used
      a full-length aversive film to elicit intense emotion on one evening, and an
      emotionally neutral control film on another evening while psychophysiological and
      experiential responses were measured. Subsequent sleep was monitored
      polysomnographically, and specific film scenes were presented again on the next
      morning. Correlation analyses revealed that participants with longer late-night
      REM sleep after the aversive film showed higher increase of electrodermal
      reactivity and less reduction of facial corrugator muscle reactivity to negative
      film scenes on the next morning. This indicates that REM sleep may be associated
      with attenuated emotional processing of prolonged and intense emotional stimuli
      from pre- to postsleep. 

PMID- 25588964
TI  - Criminalization of pregnant women with substance use disorders.

PMID- 25588963
TI  - Efficacy and safety of late-start Corifollitropin-alfa administration for
      controlled ovarian hyperstimulation in IVF: a cohort, case-control study.
AB  - OBJECTIVE: To investigate efficacy and safety of a controlled ovarian stimulation
      (COS) protocol in which a single dose of Corifollitropin-alfa (CFalpha) was
      administered on day 4 of a GnRH-antagonist cycle. DESIGN: Cohort case-control
      study. SETTING: University Hospital. PATIENTS: One hundred twenty-two normally
      cycling women expected to be normal responders to COS. INTERVENTIONS: In 61
      patients, CFalpha (100-150 MUg) was injected subcutaneously on day 4 of a
      spontaneous menstrual cycle; a GnRH-antagonist was added from day 8 (fixed
      protocol; 0.25 mg/day). If needed to complete follicular maturation, recombinant
      FSH (rFSH) daily injections (150/200 IU/day) were given from day 11. A control
      group of 61 matched women was stimulated with daily subcutaneous injections of
      rFSH (100-150 U/day) from day 4 of the cycle, and received GnRH-antagonist (0.25
      mg/day) from day 8. IVF or ICSI was performed according to the sperm
      characteristics, and 1-2 embryos were transferred in utero under US guidance on
      day 2. MAIN OUTCOME MEASURES: Number of retrieved cumulus-oocyte complexes
      (COCs), clinical pregnancy rate (PR), implantation rate (IR), ongoing PR at 10
      weeks, number of injections/cycle, ovarian hyperstimulation syndrome (OHSS) rate.
      RESULTS: No cycle was cancelled and the mean number of retrieved COCs was
      comparable in patients and controls. About 60% of CF-alfa treated women had no
      need of daily rFSH addition, and the mean number of injections/cycle was
      significantly lower in the CF-alfa group than in controls (p < 0.05). The ongoing
      PR/transfer was 36.8% in CF-alfa group and 37.5% in controls. No patient
      developed severe OHSS, and the incidence of moderate OHSS was similar in cases
      and controls. CONCLUSIONS: CFalpha may be started on day 4 of the cycle obtaining
      results comparable to those of a COS using day 4-start daily rFSH, with
      significantly less injections and a similar risk of OHSS.

PMID- 25588965
TI  - Matrix metalloproteinases (MMP-1, MMP-2, MMP-3 and MMP-9, and TIMP-1, TIMP-2 and
      TIMP-3) and markers for vascularization in functioning and non-functioning bleb
      capsules of glaucoma drainage implants.
AB  - PURPOSE: To investigate and compare functioning versus non-functioning glaucoma
      drainage implant (GDI) capsules for selective markers of extracellular matrix
      degradation and vascularity. METHODS: In three samples of both functioning and
      non-functioning blebs, immunohistochemistry was used to determine the expression
      of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, TIMP-3 and CD31. A non-functioning
      bleb was defined as IOP >21 mmHg or <20% reduction in IOP from baseline with
      maximal tolerated medication. The samples were classified into five grades based
      on immunostaining: no staining, no significant staining, mild, moderate or marked
      staining. RESULTS: Expression of MMP-1, MMP-2 and MMP-3 was mostly low in both
      functioning and non-functioning blebs. However, immunostaining of MMP-9 was
      marked in samples taken from functioning GDIs and correlated with the presence of
      vascular profiles in the luminal bleb. CD31 immunoreactivity was more intense in
      the outer layers of the bleb than in the inner layers. In non-functioning blebs,
      immunoreactivity for TIMP-3 was significant through the whole bleb wall, but only
      mild in the inner zone of functioning blebs. TIMP-1 and TIMP-2 were barely
      detectable. CONCLUSION: Staining of TIMP-3 was seen to be lower in the vicinity
      of the small blood vessels. In avascular bleb wall, increased expression of TIMP
      3 suggests its potential role in the inhibition of angiogenesis as reported
      previously in vivo. The abundance of MMP-9 in bleb capsule wall of relatively old
      patients might lead to weakened bleb capsule wall architecture and increasing
      filtration of aqueous humour through the capsule, which are reflected in a lower
      IOP.

PMID- 25588966
TI  - Effect of the number of presentations on listener transcriptions and reliability
      in the assessment of speech intelligibility in children.
AB  - BACKGROUND: The assessment of intelligibility is an essential part of
      establishing the severity of a speech disorder. The intelligibility of a speaker
      is affected by a number of different variables relating, inter alia, to the
      speech material, the listener and the listener task. AIMS: To explore the impact
      of the number of presentations of the utterances on assessments of
      intelligibility based on orthographic transcription of spontaneous speech,
      specifically the impact on intelligibility scores, reliability and intra-listener
      variability. METHODS & PROCEDURES: Speech from 12 children (aged 4:6-8:3 years;
      mean = 5:10 years) with percentage consonants correct (PCC) scores ranging from
      49 to 81 was listened to by 18 students on the speech-language pathology (SLP)
      programme and by two recent graduates from that programme. Three conditions were
      examined during the transcription phase: (1) listening to each utterance once;
      (2) listening to each utterance a second time; and (3) listening to all
      utterances from a given child a third time after having heard all of its
      utterances twice. OUTCOMES & RESULTS: Statistically significant differences
      between intelligibility scores were found across the three conditions, i.e. the
      intelligibility score increased with the number of presentations while inter
      judge reliability was unchanged. The results differed markedly across listeners,
      but each individual listener's results were very consistent across conditions.
      CONCLUSIONS & IMPLICATIONS: Information about the number of times an utterance is
      presented to the listener is important and should therefore always be included in
      reports of research involving intelligibility assessment. There is a need for
      further research and discussion on listener abilities and strategies.

PMID- 25588967
TI  - Novel Potent and Selective Acetylcholinesterase Inhibitors as Potential Drugs for
      the Treatment of Alzheimer's Disease: Synthesis, Pharmacological Evaluation, and
      Molecular Modeling of Amino-Alkyl-Substituted Fluoro-Chalcones Derivatives.
AB  - A new series of-fluoro chalcones-substituted amino-alkyl derivatives (3a~3l) were
      designed, synthesized, characterized and evaluated for the inhibitory activity
      against acetylcholinesterase and butyrylcholinesterase. The results showed that
      the alteration of fluorine atom position and amino-alkyl groups markedly
      influenced the activity and the selectivity of chalcone derivates in inhibiting
      acetylcholinesterase and butyrylcholinesterase. Among them, compound 3l possesses
      the most potent inhibitory against acetylcholinesterase (IC50  = 0.21 +/- 0.03
      MUmol/L), and the highest selectivity for acetylcholinesterase over
      butyrylcholinesterase (IC50 (BuChE)/IC50 (AChE) = 65.0). Molecular modeling and
      enzyme kinetic study on compound 3l supported its dual acetylcholinesterase
      inhibitory profile, simultaneously binding at the catalytic active and peripheral
      anionic site of the enzyme. 

PMID- 25588969
TI  - PCR assay for pathogen detection in ventriculostomy-related meningitis in
      neurosurgery patients: unanswered questions?

PMID- 25588968
TI  - Antibiotic consumption after implementation of a procalcitonin-guided
      antimicrobial stewardship programme in surgical patients admitted to an intensive
      care unit: a retrospective before-and-after analysis.
AB  - PURPOSE: To analyse antibiotic use density (AD)--World Health Organization
      defined daily doses/1,000 patient-days--before and after implementation of a
      local antimicrobial stewardship programme (ASP) in conjunction with a
      procalcitonin (PCT)-guided protocol in a surgical intensive care unit (ICU).
      METHODS: In this retrospective observational study, data on 2,422 ICU patients
      between 2010 and 2012 were analysed. In 2011, an ASP in conjunction with a PCT
      protocol had been introduced into clinical practice. In a multivariate analysis,
      hospital mortality, length of stay (LOS) in hospital and ICU LOS were adjusted
      for effects from effective cost weight, gender, and age. AD and changes in the
      use of antibiotic classes were analysed. RESULTS: AD decreased from 1,005.0 in
      2010 to 791.9 in 2012 which is a total reduction of 21.2%. Consumption of
      aminoglycosides, cephalosporins and quinolones showed a marked reduction, whereas
      the use of penicillins did not change significantly. The multivariate models
      revealed no relevant changes in mortality rate, ICU LOS and hospital LOS.
      CONCLUSIONS: Implementation of an ASP in conjunction with a PCT protocol in 2011
      was associated with a marked decrease in total AD and led to a significant change
      in the spectrum of antibiotics. Clinical outcomes appeared to remain unchanged
      over the study period.

PMID- 25588972
TI  - Successful management of refractory angiolymphoid hyperplasia with eosinophilia
      with thalidomide.

PMID- 25588971
TI  - Effects of total fibre or resistant starch-rich diets within lifestyle
      intervention in obese prediabetic adults.
AB  - PURPOSE: Starting from the evidence-based health benefits that resistant starch
      (RS) shows when added to the diet, our aim in this study was to evaluate the
      effects of increased fibre intake with two different levels of RS coming from
      regular daily consumed foods on normalization of glycaemia within lifestyle
      intervention in the population with risk factors for developing diabetes.
      METHODS: Study included 47 overweight and obese men and women with disordered
      glucoregulation and dyslipidaemia, aged between 45-74, divided into RS and Fibre
      group. Participants were subjected to the lifestyle and dietary intervention with
      low-fat and high-fibre (>25 g/day) diet for 12 months and were offered two
      different dietary advices aimed at increasing total fibre intake in Fibre group
      and at increasing RS intake in RS group. RESULTS: The intake of macronutrients
      and total fibre was similar between groups at the end of the study, but achieved
      RS intake was two times higher in the RS group. Decrease in total cholesterol and
      non-HDL-cholesterol was more pronounced in RS group in comparison with Fibre
      group (p = 0.010, p = 0.031, respectively), whereas in Fibre group, a more
      pronounced effect on glucoregulation was observed: significant fall in glycaemia
      after 2-h oral glucose tolerance test (7.93 vs 6.96 mmol/L, p = 0.034).
      CONCLUSION: At the end of the study, RS-rich diet failed to affect glycaemic
      control in prediabetic obese individuals in contrast to the regular fibre-rich
      diet, which indicated that fibre profile could be an important determinant of the
      effect of dietary intervention.

PMID- 25588973
TI  - Health workers' experiences, barriers, preferences and motivating factors in
      using mHealth forms in Ethiopia.
AB  - BACKGROUND: Mobile health (mHealth) applications, such as innovative electronic
      forms on smartphones, could potentially improve the performance of health care
      workers and health systems in developing countries. However, contextual evidence
      on health workers' barriers and motivating factors that may influence large-scale
      implementation of such interfaces for health care delivery is scarce. METHODS: A
      pretested semistructured questionnaire was used to assess health workers'
      experiences, barriers, preferences, and motivating factors in using mobile health
      forms on smartphones in the context of maternal health care in Ethiopia. Twenty
      five health extension workers (HEWs) and midwives, working in 13 primary health
      care facilities in Tigray region, Ethiopia, participated in this study. RESULTS:
      Over a 6-month period, a total of 2,893 electronic health records of 1,122 women
      were submitted to a central computer through the Internet. Sixteen (69.6%)
      workers believed the forms were good reminders on what to do and what questions
      needed to be asked. Twelve (52.2%) workers said electronic forms were
      comprehensive and 9 (39.1%) workers saw electronic forms as learning tools. All
      workers preferred unrestricted use of the smartphones and believed it helped them
      adapt to the smartphones and electronic forms for work purposes. With regards to
      language preference, 18 (78.3%) preferred using the local language (Tigrinya)
      version of the forms to English. Indentified barriers for not using electronic
      forms consistently include challenges related to electronic forms (for example,
      problem with username and password setting as reported by 5 (21.7%), smartphones
      (for example, smartphone froze or locked up as reported by 9 (39.1%) and health
      system (for example, frequent movement of health workers as reported by 19
      (82.6%)). CONCLUSIONS: Both HEWs and midwives found the electronic forms on
      smartphones useful for their day-to-day maternal health care services delivery.
      However, sustainable use and implementation of such work tools at scale would be
      daunting without providing technical support to health workers, securing mobile
      network airtime and improving key functions of the larger health system.

PMID- 25588974
TI  - Optic Neuritis and the Visual Pathway: Evaluation of Neuromyelitis Optica
      Spectrum by Resting-State fMRI and Diffusion Tensor MRI.
AB  - BACKGROUND AND PURPOSE: Optic neuritis (ON) is an acute episode of inflammation
      in the visual pathway (VP). It may occur as part of a demyelinating disease,
      which can affect white matter (WM) throughout the VP. Compensatory cortical
      adaptations may occur following WM damage to maintain visual integrity. Our aim
      was to investigate whether resting-state functional MRI (rsfMRI) can detect
      cortical adaptations following ON attacks and to correlate rsfMRI with diffusion
      tensor imaging (DTI) of WM within the VP. MATERIALS AND METHODS: Neuromyelitis
      optica spectrum patients were compared to healthy controls at least 6 months
      after ON onset. DTI and rsfMRI were performed and post-processed using FSL tools
      (TBSS for DTI and MELODIC for fMRI). RESULTS: Ptients had higher synchronization
      values than controls in the visual network (3.48 vs. 2.12, P < .05). A weak trend
      of correlation was revealed between fMRI and structural analysis by DTI using
      fractional anisotropy (right side: R = -.36, P < .08; left side: R = .075, P <
      .73). CONCLUSIONS: The rsfMRI detected cortical reorganization following ON
      attack, but WM was considerably preserved in the posterior VP.

PMID- 25588976
TI  - Doctors are sceptical about Indian Medical Association's new code of conduct for
      hospitals.

PMID- 25588977
TI  - ERRATUM: A reduction in reactive oxygen species contributes to dihydromyricetin
      induced apoptosis in human hepatocellular carcinoma cells.

PMID- 25588978
TI  - Lead and cadmium in raw buffalo, cow and ewe milk from west Azerbaijan, Iran.
AB  - In this study, 300 raw buffalo, cow and ewe milk samples from five townships in
      west Azerbaijan, Iran, were analysed. Lead and cadmium were determined using
      atomic absorption spectrophotometry. Mean concentration of lead and cadmium in
      buffalo milk samples was 0.018 +/- 0.001 and 0.003 +/- 0.001 mg/kg, respectively.
      Mean concentration of lead and cadmium in cow milk samples was 0.007 +/- 0.001
      and 0.001 +/- 0.001 mg/kg, respectively, and in ewe milk, these mean values were
      0.010 +/- 0.001 and 0.002 +/- 0.001 mg/kg, respectively. Statistical analyses
      showed that lead and cadmium concentrations in buffalo milk were significantly
      higher than those in cow and ewe milk. Moreover, the concentration of these heavy
      metals in ewe milk was significantly higher than that in cow milk. It was also
      found that concentration of these selected toxic metals in milk increased with
      increasing age of the animals.

PMID- 25588975
TI  - Regulation of vascular tone and arterial blood pressure: role of chloride
      transport in vascular smooth muscle.
AB  - Recent studies suggest that primary changes in vascular resistance can cause
      sustained changes in arterial blood pressure. In this review, we summarize
      current knowledge about Cl(-) homeostasis in vascular smooth muscle cells. Within
      vascular smooth muscle cells, Cl(-) is accumulated above the electrochemical
      equilibrium, causing Cl(-) efflux, membrane depolarization, and increased
      contractile force when Cl(-) channels are opened. At least two different
      transport mechanisms contribute to raise [Cl(-)] i in vascular smooth muscle
      cells, anion exchange, and cation-chloride cotransport. Recent work suggests that
      TMEM16A-associated Ca(2+)-activated Cl(-) currents mediate Cl(-) efflux in
      vascular smooth muscle cells leading to vasoconstriction. Additional proteins
      associated with Cl(-) flux in vascular smooth muscle are bestrophins, which
      modulate vasomotion, the volume-activated LRRC8, and the cystic fibrosis
      transmembrane conductance regulator (CFTR). Cl(-) transporters and Cl(-) channels
      in vascular smooth muscle cells (VSMCs) significantly contribute to the
      physiological regulation of vascular tone and arterial blood pressure. 

PMID- 25588979
TI  - Dynamics of Radical Ion Pairs following Photoinduced Electron Transfer in
      Solvents with Low and Intermediate Polarities.
AB  - Fluorescence quenching of p-xylene, naphthalene, or pyrene by fumaronitrile in
      apolar solvents and in solvents of intermediate polarities leads to weakly
      fluorescent radical ion pairs. This emission is assigned to ion pairs in close
      contact on the basis of their solvent polarity dependence, kinetics, and
      thermodynamics. The temperature-dependence of the intensity and fluorescence
      emission maxima of ion pairs in methyl acetate reveals that they have decay
      channels competitive with their thermal equilibration. The results presented in
      this work are consistent with the direct formation of contact ion pairs in weakly
      polar solvents and in solvents of intermediate polarities as the result of
      bimolecular photoinduced electron transfer reactions between aromatic
      hydrocarbons and nitriles. The implications of these findings in free-energy
      relationships of electron transfer reactions are discussed. 

PMID- 25588980
TI  - Inhibition of MiR-199a-5p reduced cell proliferation in autosomal dominant
      polycystic kidney disease through targeting CDKN1C.
AB  - BACKGROUND: With a prevalence of about 1:500 to 1:1,000, autosomal dominant
      polycystic kidney disease (ADPKD) often causes renal failure, with many serious
      complications. However, there is no Food and Drug Administration (FDA) approved
      therapy available. MATERIAL/METHODS: MiR-199a-5p level in ADPKD patient samples,
      rat model, and cell lines were determined with Realtime PCR assay. After miR-199a
      5p inhibitor was transfected, we detected the cell proliferation and apoptosis
      using an MTT assay and an Annexin V-FITC staining kit, respectively. Finally,
      TargetScan version 5.1 was used to predict the miRNA target and the target gene
      of miR-199a-5p was proved by a Luciferase assay. RESULTS: We identified a
      dramatically up-regulated microRNA, miR-199a-5p, in ADPKD tissues and cell lines.
      Our data show that inhibition of miR-199a-5p suppressed cyst cells proliferation
      and induced cell apoptosis. We found that miR-199a-5p might exert this effect
      through targeting CDKN1C/p57. CONCLUSIONS: Up-regulation of miR-199a-5p in ADPKD
      tissues might promote cell proliferation through suppressing CDKN1C, suggesting
      miR-199a-5p as a novel target for ADPKD treatment.

PMID- 25588981
TI  - Radiologic assessment of glenohumeral relationship: reliability and
      reproducibility of lateral humeral offset.
AB  - BACKGROUND: It has been shown that anatomical reconstruction is an important step
      in achieving good function after shoulder arthroplasty. It is essential to
      reconstruct the distance between the coracoid process and greater tubercle as
      this relates to the moment arm of the deltoid and rotator cuff muscles. This
      study evaluated the reliability of measurement of the lateral humeral offset
      (LHO) on plain radiographs and on computed tomography (CT). METHODS: Four
      independent observers performed measurements of LHO on radiographs and CT from 26
      patients awaiting shoulder reconstruction. The interobserver reliability and
      intraobserver reproducibility were assessed. RESULTS: Interobserver reliability
      and intraobserver reproducibility of LHO in axial CT scans were excellent. Plain
      radiography showed fair to excellent interobserver reliability and variable
      intraobserver reproducibility. CONCLUSION: CT is a reliable tool to measure LHO
      supporting its use in preoperative planning. When AP radiography is used for
      preoperative planning the examiner should be aware of its limitations and
      standardisation protocols should be considered.

PMID- 25588982
TI  - Molecular characterization of a defensin gene from a hard tick, Dermacentor
      silvarum.
AB  - BACKGROUND: Ticks are distributed worldwide and considered as vectors of many
      human diseases. Tick defensins, a family of antimicrobial peptides, form the
      first line of defense against pathogens. FINDINGS: A defensin-like gene, named Ds
      defensin, was identified from a cDNA library of the hard tick Dermacentor
      silvarum collected from northeast China. The full-length cDNA of Ds-defensin was
      225 bp, encoding a 74 amino acid peptide. The nucleotide sequence of Ds-defensin
      shared 98.2% similarity to putative defensin from Dermacentor marginatus. RT-PCR
      results suggested that Ds-defensin was extensively expressed in tick salivary
      gland and midgut, with a higher expression level in midgut. Ds-defensin showed
      broad antimicrobial activity against various Gram-positive and Gram-negative
      bacteria, as well as the fungus Candida albicans. CONCLUSIONS: We characterized a
      functional defensin from D. silvarum of China. Ds-defensin showed bactericidal
      activity against various Gram-positive and Gram-negative bacteria. Ds-defensin
      can be expected to be introduced to the medical field as a new molecule with
      antibacterial activity.

PMID- 25588983
TI  - External validation of the HIT Expert Probability (HEP) score.
AB  - The diagnosis of heparin-induced thrombocytopenia (HIT) can be challenging. The
      HIT Expert Probability (HEP) Score has recently been proposed to aid in the
      diagnosis of HIT. We sought to externally and prospectively validate the HEP
      score. We prospectively assessed pre-test probability of HIT for 51 consecutive
      patients referred to our Consultative Service for evaluation of possible HIT
      between August 1, 2012 and February 1, 2013. Two Vascular Medicine fellows
      independently applied the 4T and HEP scores for each patient. Two independent HIT
      expert adjudicators rendered a diagnosis of HIT likely or unlikely. The median
      (interquartile range) of 4T and HEP scores were 4.5 (3.0, 6.0) and 5 (3.0, 8.5),
      respectively. There were no significant differences between area under receiver
      operating characteristic curves of 4T and HEP scores against the gold standard,
      confirmed HIT [defined as positive serotonin release assay and positive anti
      PF4/heparin ELISA] (0.74 vs 0.73, p = 0.97). HEP score >= 2 was 100 % sensitive
      and 16 % specific for determining the presence of confirmed HIT while a 4T score
      > 3 was 93 % sensitive and 35 % specific. In conclusion, the HEP and 4T scores
      are excellent screening pre-test probability models for HIT, however, in this
      prospective validation study, test characteristics for the diagnosis of HIT based
      on confirmatory laboratory testing and expert opinion are similar. Given the
      complexity of the HEP scoring model compared to that of the 4T score, further
      validation of the HEP score is warranted prior to widespread clinical acceptance.

PMID- 25588984
TI  - Expression of basolateral organic anion and cation transporters in experimental
      cadmium nephrotoxicity in rat kidney.
AB  - Cadmium (Cd)-intoxicated experimental animals exhibit impaired renal secretion of
      organic anions (OA) and cations (OC), indicating their transporters (Oats and
      Octs) in the proximal tubule (PT) basolateral membrane as possible targets of Cd.
      To correlate transport data from the literature with the expression of relevant
      transporters, we performed immunochemical and RT-PCR studies of renal Oats and
      Octs in the subchronic (treatment with CdCl2; 2 mg Cd/kg b.m./day, for 2 weeks)
      and acute (treatment with Cd-metallothionein (CdMT); 0.4 mg Cd/kg b.m., 6 or 12 h
      before killing) models of Cd nephrotoxicity. In the subchronic model, PT
      exhibited a minor loss of basolateral invaginations and overall unchanged
      expression of Na(+)/K(+)-ATPase and GAPDH proteins and mRNAs, while the
      expression of Oat and Oct proteins and their mRNAs was strongly downregulated. In
      the acute model, a time-related redistribution of basolateral transporters to the
      intracellular vesicular compartment was a major finding. However, 6 h following
      CdMT treatment, the total abundance of Oat and Oct proteins in the renal tissue
      remained unchanged, the expression of mRNAs decreased only for Oats, while a
      limited Oat1 and Na(+)/K(+)-ATPase immunoreactivity in the PT apical membrane
      indicated loss of cell polarity. As tested in rats treated with colchicine, the
      observed loss/redistribution of basolateral transporters in both models may be
      independent on microtubules. Therefore, the diminished renal secretion of OA and
      OC via PT in Cd nephrotoxicity may result from (a) limited loss of secretory
      surface (basolateral invaginations), (b) selective loss of Oats and Octs, and

PMID- 25588986
TI  - A bright future for Hormones and Cancer: farewell comments of Dr. Carol A. Lange,
      recent past Editor-in-Chief.

PMID- 25588985
TI  - Perfluorononanoic acid in combination with 14 chemicals exerts low-dose mixture
      effects in rats.
AB  - Humans are simultaneously exposed to several chemicals that act jointly to induce
      mixture effects. At doses close to or higher than no-observed adverse effect
      levels, chemicals usually act additively in experimental studies. However, we are
      lacking knowledge on the importance of exposure to complex real-world mixtures at
      more relevant human exposure levels. We hypothesised that adverse mixture effects
      occur at doses approaching high-end human exposure levels. A mixture (Mix) of 14
      chemicals at a combined dose of 2.5 mg/kg bw/day was tested in combination with
      perfluorononanoic acid (PFNA) at doses of 0.0125 (Low PFNA), 0.25 (Mid PFNA) and
      5 (High PFNA) mg/kg bw/day by oral administration for 14 days in juvenile male
      rats. Indication of a toxicokinetic interaction was found, as simultaneous
      exposure to PFNA and the Mix caused a 2.8-fold increase in plasma PFNA
      concentrations at Low PFNA. An increase in testosterone and dihydrotestosterone
      plasma concentrations was observed for Low PFNA + Mix. This effect was considered
      non-monotonic, as higher doses did not cause this effect. Reduced LH plasma
      concentrations together with increased androgen concentrations indicate a
      disturbed pituitary-testis axis caused by the 15-chemical mixture. Low PFNA by
      itself increased the corticosterone plasma concentration, an effect which was
      normalised after simultaneous exposure to Mix. This combined with affected ACTH
      plasma concentrations and down-regulation of 11beta HSD mRNA in livers indicates
      a disturbed pituitary-adrenal axis. In conclusion, our data suggest that mixtures
      of environmental chemicals at doses approaching high-end human exposure levels
      can cause a hormonal imbalance and disturb steroid hormones and their regulation.
      These effects may be non-monotonic and were observed at low doses. Whether this
      reflects a more general phenomenon that should be taken into consideration when
      predicting human mixture effects or represents a rarer phenomenon remains to be
      shown.

PMID- 25588987
TI  - Influence of the beta-sheet content on the mechanical properties of aggregates
      during amyloid fibrillization.
AB  - Amyloid fibrils associated with neurodegenerative diseases, such as Parkinson's
      and Alzheimer's, consist of insoluble aggregates of alpha-synuclein and Abeta-42
      proteins with a high beta-sheet content. The aggregation of both proteins occurs
      by misfolding of the monomers and proceeds through the formation of intermediate
      oligomeric and protofibrillar species to give the final fibrillar cross-beta
      sheet structure. The morphological and mechanical properties of oligomers,
      protofibrils, and fibrils formed during the fibrillization process were
      investigated by thioflavin T fluorescence and circular dichroism in combination
      with AFM peak force quantitative nanomechanical technique. The results reveal an
      increase in the Young's modulus during the transformation from oligomers to
      mature fibrils, thus inferring that the difference in their mechanical properties
      is due to an internal structural change from a random coil to a structure with
      increased beta-sheet content. 

PMID- 25588988
TI  - Breadfruit (Artocarpus altilis): a source of high-quality protein for food
      security and novel food products.
AB  - Protein deficiency has been observed as a leading cause of malnutrition and child
      death in the tropics. The current study evaluated the protein quality of 49
      important breadfruit cultivars (41 Artocarpus altilis and 8 hybrids of A. altilis
      * A. mariannensis). While significant differences were found between cultivars,
      all varieties contained a full spectrum of the essential amino acids and are
      especially rich in phenylalanine, leucine, isoleucine, and valine. The cultivar
      Ma'afala contained significantly higher total essential amino acid content than
      other varieties and higher-quality protein than staples such as corn, wheat,
      rice, soybean, potato, and pea. 

PMID- 25588989
TI  - Use of medication algorithms in first episode psychosis: a naturalistic
      observational study.
AB  - AIMS: Medical algorithms are evidence-based guidelines which help physicians to
      make their decisions regarding treatment. Non-adherence to medical algorithms is
      a matter of concern. The aims of this study were to investigate physicians'
      adherence to an algorithm for antipsychotics, patients' adherence to the
      physicians' recommendations and whether these factors influence one year outcome.
      METHOD: An extensive file audit survey was conducted among 55 consecutively first
      admitted inpatients and outpatients from three units of a university hospital;
      looking at the prescription of antipsychotics to patients (15-65 years)
      experiencing first episode psychosis (F19.5, F20.0-F29.0 according to ICD-10).
      Inclusion period was 2 years. Data on clinical condition and use of drugs were
      collected from the electronic patient administrative record system and from each
      patient's medical record for 12 months. RESULTS: Only 62% of the physicians
      adhered to the medical algorithm, although all first choices of drugs were made
      according to international standards. Fifty-six percent of patients used their
      medicine more than 75% of the time, 22% had between 26% and 74% adherence and 22%
      adhered less than 25%. Patient adherence was significantly associated with good
      outcome. Older patients and inpatients had more favourable outcomes than younger
      patients and outpatients. Physicians at inpatient wards initiated pharmacological
      treatment significantly earlier than physicians in outpatient departments. The
      most common first antipsychotic drug to prescribe was olanzapine followed by
      risperidone. CONCLUSION: Initial medical intervention followed international
      standards, but the physicians failed to adhere to algorithms in their follow-up
      of medication regimes. Adherence was associated with outcome.

PMID- 25588991
TI  - The ligand field of the azido ligand: insights into bonding parameters and
      magnetic anisotropy in a Co(II)-azido complex.
AB  - The azido ligand is one of the most investigated ligands in magnetochemistry.
      Despite its importance, not much is known about the ligand field of the azido
      ligand and its influence on magnetic anisotropy. Here we present the electronic
      structure of a novel five-coordinate Co(II)-azido complex (1), which has been
      characterized experimentally (magnetically and by electronic d-d absorption
      spectroscopy) and theoretically (by means of multireference electronic structure
      methods). Static and dynamic magnetic data on 1 have been collected, and the
      latter demonstrate slow relaxation of the magnetization in an applied external
      magnetic field of H = 3000 Oe. The zero-field splitting parameters deduced from
      static susceptibility and magnetizations (D = -10.7 cm(-1), E/D = 0.22) are in
      excellent agreement with the value of D inferred from an Arrhenius plot of the
      magnetic relaxation time versus the temperature. Application of the so-called N
      electron valence second-order perturbation theory (NEVPT2) resulted in excellent
      agreement between experimental and computed energies of low-lying d-d
      transitions. Calculations were performed on 1 and a related four-coordinate
      Co(II)-azido complex lacking a fifth axial ligand (2). On the basis of these
      results and contrary to previous suggestions, the N3(-) ligand is shown to behave
      as a strong sigma and pi donor. Magnetostructural correlations show a strong
      increase in the negative D with increasing Lewis basicity (shortening of the Co-N
      bond distances) of the axial ligand on the N3(-) site. The effect on the change
      in sign of D in going from four-coordinate Co(II) (positive D) to five-coordinate
      Co(II) (negative D) is discussed in the light of the bonding scheme derived from
      ligand field analysis of the ab initio results. 

PMID- 25588997
TI  - Theranostic mercury: (197(m))Hg with high specific activity for imaging and
      therapy.
AB  - The no carrier added (NCA) radionuclide (197(m))Hg is accessible through proton
      induced nuclear reactions on gold. The decay properties of both simultaneous
      produced nuclear isomers (197m)Hg and (197)Hg like convenient half life, low
      energy gamma radiations for imaging, Auger and conversion electrons for therapy
      are combined with unique chemical and physical properties of mercury and its
      compounds. Gold as a monoisotopic element has a natural abundance of 100% (197)Au
      superseding expensive enrichment for the target material. Additionally, the high
      thermal conductivity of gold enables high beam current irradiations. For
      separation of target material a liquid-liquid extraction method was applied. 

PMID- 25588998
TI  - Relationships between dipole moments of diatomic molecules.
AB  - The dipole moment is one of the most important physical properties of a molecule.
      We present a combination rule for the dipole moments of related diatomic
      molecules. For molecules AB, AX, BY, and XY from two different element groups in
      the periodic table, if their elements make a small parallelogram, reliable
      predictions can be obtained. Our approach is particularly useful for systems with
      heavy atoms. For a large set of molecules tested, the average difference of the
      prediction from experimental data is less than 0.2 debye (D). The dipole moments
      for heavy molecules such as GaCl, InBr, SrCl, and SrS, for which no experimental
      data are available at present, are predicted to be 3.17, 3.76, 3.85 and 11.54 D,
      respectively. 

PMID- 25588992
TI  - Increased locomotor and thermogenic activity in mice with targeted ablation of
      the GHRH gene.
AB  - OBJECTIVE: Growth hormone (GH) deficiency (GHD) leads to growth failure and
      changes in body composition, including increased fat accumulation and reduced
      lean body mass in both humans and rodents. The aim of this study was to examine
      the factors that contribute to energy imbalance in the GH releasing hormone knock
      out (GHRHKO) mice, a well established model of GHD. DESIGN: We evaluated food
      intake (of standard laboratory chow), total body weight (TBW), locomotor
      activity, body temperature and interscapular brown adipose tissue (BAT) weight in
      8 adult male mice homozygous for the GHRHKO allele (-/-) and 8 heterozygous (+/-)
      animals as controls. The gene expression of uncoupling protein-1 (UCP-1) in BAT
      and the levels of norepinephrine (NE), dopamine (DA), and serotonin (5
      hydroxytryptamine, 5-HT) in the ventral striatum were measured by real-time
      reverse transcription polymerase chain reaction (RT-PCR) and high performance
      liquid chromatography (HPLC) analysis, respectively. RESULTS: Throughout 2 months
      of observation -/- mice consumed approximately 40% more food (normalized to TBW;
      P<0.001), and showed increased locomotor activity in 24h time compared to
      controls (P<0.05). Moreover, -/- animals showed increased body temperature
      (P<0.001), BAT weight (P<0.001), and UCP-1 gene expression (P<0.001), while NE
      levels in the striatum area were lower (P<0.05) than controls. CONCLUSIONS: The
      present study demonstrates that the increased food intake observed in GHRH
      ablated animals is associated with increased locomotor and thermogenic activity.

PMID- 25588999
TI  - Promoting Ecohealth through Geography and Governmental Partnerships.

PMID- 25588990
TI  - Disruption of SUMO-targeted ubiquitin ligases Slx5-Slx8/RNF4 alters RecQ-like
      helicase Sgs1/BLM localization in yeast and human cells.
AB  - RecQ-like helicases are a highly conserved protein family that functions during
      DNA repair and, when mutated in humans, is associated with cancer and/or
      premature aging syndromes. The budding yeast RecQ-like helicase Sgs1 has
      important functions in double-strand break (DSB) repair of exogenously induced
      breaks, as well as those that arise endogenously, for example during DNA
      replication. To further investigate Sgs1's regulation, we analyzed the
      subcellular localization of a fluorescent fusion of Sgs1 upon DNA damage.
      Consistent with a role in DSB repair, Sgs1 recruitment into nuclear foci in
      asynchronous cultures increases after ionizing radiation (IR) and after exposure
      to the alkylating agent methyl methanesulfonate (MMS). Yet, despite the
      importance of Sgs1 in replicative damage repair and in contrast to its elevated
      protein levels during S-phase, we find that the number of Sgs1 foci decreases
      upon nucleotide pool depletion by hydroxyurea (HU) treatment and that this
      negative regulation depends on the intra S-phase checkpoint kinase Mec1.
      Importantly, we identify the SUMO-targeted ubiquitin ligase (STUbL) complex Slx5
      Slx8 as a negative regulator of Sgs1 foci, both spontaneously and upon
      replicative damage. Slx5-Slx8 regulation of Sgs1 foci is likely conserved in
      eukaryotes, since expression of the mammalian Slx5-Slx8 functional homologue,
      RNF4, restores Sgs1 focus number in slx8 cells and furthermore, knockdown of RNF4
      leads to more BLM foci in U-2 OS cells. Our results point to a model where RecQ
      like helicase subcellular localization is regulated by STUbLs in response to DNA
      damage, presumably to prevent illegitimate recombination events. 

PMID- 25589000
TI  - Age at Vaccination May Influence Response to Sylvatic Plague Vaccine (SPV) in
      Gunnison's Prairie Dogs (Cynomys gunnisoni).
AB  - Gunnison's prairie dogs (Cynomys gunnisoni) have been considered at greater risk
      from Yersinia pestis (plague) infection in the montane portion of their range
      compared to populations at lower elevations, possibly due to factors related to
      flea transmission of the bacteria or greater host susceptibility. To test the
      latter hypothesis and determine whether vaccination against plague with an oral
      sylvatic plague vaccine (SPV) improved survival, we captured prairie dogs from a
      C. g. gunnisoni or "montane" population and a C. g. zuniensis or "prairie"
      population for vaccine efficacy and challenge studies. No differences (P = 0.63)
      were found in plague susceptibility in non-vaccinated animals between these two
      populations; however, vaccinates from the prairie population survived plague
      challenge at significantly higher rates (P < 0.01) than those from the montane
      population. Upon further analysis, we determined that response to immunization
      was most likely associated with differences in age, as the prairie group was much
      younger on average than the montane group. Vaccinates that were juveniles or
      young adults survived plague challenge at a much higher rate than adults (P <
      0.01 and P = 0.02, respectively), but no difference (P = 0.83) was detected in
      survival rates between control animals of different ages. These results suggest
      that host susceptibility is probably not related to the assumed greater risk from
      plague in the C. g. gunnisoni or "montane" populations of Gunnison's prairie
      dogs, and that SPV could be a useful plague management tool for this species,
      particularly if targeted at younger cohorts. 

PMID- 25589002
TI  - Second Morning ACR Could Be the Alternative to First Morning ACR to Assess
      Albuminuria in Elderly Population.
AB  - BACKGROUND: Albumin/creatinine ratio (ACR) from a first morning urine is
      recommended as a early indicator for diabetic nephropathy. However, it is not
      always feasible to collect the first morning urine for outpatients. We aimed to
      explore whether ACR from a second morning urine had a good consistency with that
      from a first morning urine to predict albuminuria in Chinese elderly citizens.
      METHOD: One hundred and ninety-one elderly citizens (?60 years old) from
      Junliangcheng community, Dongli district, Tianjin, China were included. A first
      and second morning urine was collected from each participants, successfully and
      detected the urinary albumin and creatinine of each urine sample. Albumin to
      creatinine ratio from a first morning urine (ACR1) was compared with that from a
      second morning urine (ACR2), and the ability of ACR1 and ACR2 to predict
      albuminuria was assessed. RESULT: ACR1 and ACR2 were highly correlated (r =
      0.901), especially in male and hypertension group (r = 0.938 and 0.904). The
      slope and intercept were 0.93 and 0.11 after log-transformed. And there was no
      statistical difference between values of ACR1 and ACR2 (P = 0.271). Overall,
      26.2% participants were detected with albuminuria when judged by ACR1 and 28.3%
      by ACR2. A good concordance of ACR category (normal or albuminuria) was found
      between ACR1 and ACR2 (Kappa value = 0.815 in overall; in male and hypertension
      group were 0.900 and 0.850). CONCLUSION: A second morning urine ACR could be the
      alternative to a first morning urine ACR for albuminuria detection in elderly
      population.

PMID- 25589001
TI  - Body weight and risk of atrial fibrillation in 7,169 patients with newly
      diagnosed type 2 diabetes; an observational study.
AB  - BACKGROUND: Obesity, type 2 diabetes and atrial fibrillation (AF) are closely
      associated, but the underlying mechanisms are not fully understood. We aimed to
      explore associations between body mass index (BMI) or weight change with risk of
      AF in patients with type 2 diabetes. METHODS: A total of 7,169 participations
      with newly diagnosed type 2 diabetes were stratified according to baseline BMI,
      and after a second BMI measurement within 18 months, further grouped according to
      relative weight change as "weight gain" (>1 BMI unit), "stable weight" (+/- 1 BMI
      unit) and "weight loss" (<1 BMI unit). The mean follow-up period was 4.6 years,
      and the risk of AF was estimated using adjusted Cox regression models. RESULTS:
      Average age at diabetes diagnosis was 60 years and the patients were slightly
      obese (mean BMI 30.2 kg/m(2)). During follow-up, 287 patients developed incident
      AF, and those with overweight or obesity at baseline had 1.9-fold and 2.9-fold
      higher risk of AF, respectively, than those with normal BMI. The 14% of the
      patients with subsequent weight gain had 1.5-fold risk of AF compared with those
      with stable weight or weight loss. CONCLUSIONS: In patients with newly diagnosed
      type 2 diabetes, baseline overweight and obesity, as well as modest weight
      increase during the first 18 months after diagnosis, were associated with a
      substantially increased risk of incident AF. Patients with type 2 diabetes may
      benefit from efforts to prevent weight gain in order to reduce the risk of
      incident AF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01121315.

PMID- 25589003
TI  - Sporadic hemangioblastomas are characterized by cryptic VHL inactivation.
AB  - Hemangioblastomas consist of 10-20% neoplastic "stromal" cells within a vascular
      tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial
      cases of central nervous system hemangioblastoma uniformly result from mutations
      in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been
      previously observed in only a minority of sporadic hemangioblastomas, suggesting
      an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32
      sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n =
      22), followed by analysis of clonality, copy number alteration, and somatic
      mutation. We identified somatic mutation, loss of heterozygosity and/or deletion
      of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were
      ultimately detected in 78% (25/32) of cases. No other gene was significantly
      mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL
      alterations within the neoplastic fraction of these tumors at higher frequencies
      than previously reported. Our findings support the central role of VHL
      inactivation in the molecular pathogenesis of both familial and sporadic
      hemangioblastomas.

PMID- 25589004
TI  - Clinicopathological and Prognostic Significance of CD133 in Glioma Patients: A
      Meta-Analysis.
AB  - In recent years, CD133 has been identified as a cancer stem cell (CSC) marker in
      gliomas. Nevertheless, the clinical and prognostic value of CD133 in glioma
      patients remains controversial. Therefore, we conducted a systematic meta
      analysis to evaluate the correlation of CD133 with World Health Organization
      (WHO) grade, age, gender, overall survival (OS), and progression-free survival
      (PFS) in glioma patients. Eligible studies on this subject were included, and
      then pooled odd ratios (ORs) and hazard ratios (HRs) with 95 % confidence
      intervals (95 % CIs) were estimated. Publication bias was assessed by the funnel
      plots, and heterogeneity and sensitivity were analyzed as well. In the present
      study, 21 articles with the total number of 1535 patients were included. High
      expression of CD133 in glioma patients was associated with high WHO grade (III +
      IV) (n = 11, OR 5.10, 95 % CI 2.99-8.69; p = 0.000), rather than age (n = 4, OR
      2.54, 95 % CI 0.68-9.52; p = 0.167) and gender (n = 4, OR 0.71, 95 % CI 0.21
      2.45; p = 0.587). In addition, survival analysis demonstrated a significant
      association between CD133 high expression and poor 2-year OS (n = 11, HR 2.18, 95
      % CI 1.29-3.7; p = 0.004), 5-year OS (n = 4, HR 10.39, 95 % CI 2.59-41.63; p =
      0.001), as well as PFS (n = 10, HR 2.34, 95 % CI 1.62-3.37; p = 0.000). Taken
      together, this study suggests that CD133 expression correlates to higher grade of
      gliomas and worse prognosis in glioma patients. Thus, CD133 could be recommended
      as a useful pathological and prognostic biomarker in clinical practice.

PMID- 25589006
TI  - [The hospital emergency plan].
AB  - STRUCTURE: The hospital emergency plan consists of a basic plan and an appendix.
      The basic plan deals with the general aspects of emergency operation and the
      special aspects of external and internal emergencies. The appendix contains
      special instructions, e.g., emergency action orders, staff alert lists, material
      lists, and situation plans. CONTENT AND IMPLEMENTATION: External emergencies
      (e.g., mass casualty incidents) and internal emergencies (e.g., fire and other
      environmental threats) should be regarded. Once a defined experienced physician
      decides to activate the emergency plan, the hospital changes from routine to
      emergency service. Due to its security significance, the emergency plan should be
      regarded as confidential. MANDATORY REQUIREMENTS: A two-tier chain of command is
      implemented: the hospital staff deals with administrational and organizational
      aspects, whereas the subsequent medical staff is in charge of immediate patient
      care. Repeated updating and exercises are necessary. Furthermore, a basic
      logistic autonomy of the hospital is essential.

PMID- 25589007
TI  - Practical synthesis of anti-beta-hydroxy-alpha-amino acids by Pd(II) -catalyzed
      sequential C(sp(3) )-H functionalization.
AB  - An improved and practical procedure for the stereoselective synthesis of anti
      beta-hydroxy-alpha-amino acids (anti-betahAAs), by palladium-catalyzed sequential
      C(sp(3) )-H functionalization directed by 8-aminoquinoline auxiliary, is
      described. followed by a previously established monoarylation and/or alkylation
      of the beta-methyl C(sp(3) )-H of alanine derivative, beta-acetoxylation of both
      alkylic and benzylic methylene C(sp(3) )-H bonds affords various anti-beta
      hydroxy-alpha-amino acid derivatives. As an example, the synthesis of beta
      mercapto-alpha-amino acids, which are highly important to the extension of native
      chemical ligation chemistry beyond cysteine, is described. The synthetic
      potential of this protocol is further demonstrated by the synthesis of diverse
      beta-branched alpha-amino acids. The observed diastereoselectivities are strongly
      influenced by electronic effects of aromatic AAs and steric effects of the linear
      side-chain AAs, which could be explained by the competition of intramolecular C
      OAc bond reductive elimination from Pd(IV) intermediates vs. intermolecular
      attack by an external nucleophile (AcO(-) ) in an SN 2-type process.

PMID- 25589005
TI  - Prevention of Photocarcinogenesis by Agonists of 5-HT1A and Antagonists of 5-HT2A
      Receptors.
AB  - Exposure to UV radiation is the principal cause of nonmelanoma skin cancer, a
      process in which serotonin (5-HT) is intimately involved. This review focuses on
      the potential of serotonin receptors, namely 5-HT1/2A, as therapeutic targets for
      prevention of photocarcinogenesis. UV-induced immunosuppression is triggered by a
      cascade of events initiated when cis-urocanic acid, a UV photoreceptor present in
      the skin, binds to the serotonin receptor. Serotonin receptor antagonists will
      therefore attempt to block this association, and in turn, prevent skin cancer
      induction. In addition, 5-HT2A receptor antagonists are also capable of
      regulating DNA repair, including the acceleration of nucleotide excision repair.
      At the same time, UV-induced formation of reactive oxygen species is also reduced
      by these agents. Since the involvement of serotonin in photocarcinogenesis
      process is somewhat underexplored as a pertinent therapeutic effect, this review
      intends to reveal the use of serotonergic drugs as an important strategy to
      prevent and/or inhibit photocarcinogenesis. Considering the emergency of
      developing novel therapeutic strategies for skin cancer management, the use of
      these agents, whose benefits have partially been studied, may be crucial
      especially if topically applied. Topical nanoformulations containing serotonin
      receptor agonists and/or antagonists also represent a pioneer concept in this
      area. Graphical Abstract ?. 

PMID- 25589008
TI  - Fungistatic activity of Zanthoxylum rhoifolium Lam. bark extracts against fungal
      plant pathogens and investigation on mechanism of action in Botrytis cinerea.
AB  - Plant-derived compounds are emerging as an alternative choice to synthetic
      fungicides. Chloroform-methanol extract, obtained from the bark of Zanthoxylum
      rhoifolium, a member of Rutaceae, showed a fungistatic effect on Botrytis
      cinerea, Sclerotinia sclerotiorum, Alternaria alternata, Colletotrichum
      gloeosporioides and Clonostachys rosea, when added to the growth medium at
      different concentrations. A fraction obtained by gel separation and containing
      the alkaloid O-Methylcapaurine showed significant fungistatic effect against B.
      cinerea and S. sclerotiorum, two of the most destructive phytopathogenic fungi.
      The underlying mechanism of such an inhibition was further investigated in B.
      cinerea, a fungus highly prone to develop fungicide resistance, by analysing the
      expression levels of a set of genes (BcatrB, P450, CYP51 and TOR). O
      Methylcapaurine inhibited the expression of all the analysed genes. In
      particular, the expression of BcatrB gene, encoding a membrane drug transporter
      involved in the resistance to a wide range of xenobiotic compounds, was strongly
      inhibited (91%). 

PMID- 25589009
TI  - An observational study of social and emotional support in smoking cessation
      Twitter accounts: content analysis of tweets.
AB  - BACKGROUND: Smoking continues to be the number one preventable cause of premature
      death in the United States. While evidence for the effectiveness of smoking
      cessation interventions has increased rapidly, questions remain on how to
      effectively disseminate these findings. Twitter, the second largest online social
      network, provides a natural way of disseminating information. Health
      communicators can use Twitter to inform smokers, provide social support, and
      attract them to other interventions. A key challenge for health researchers is
      how to frame their communications to maximize the engagement of smokers.
      OBJECTIVE: Our aim was to examine current Twitter activity for smoking cessation.
      METHODS: Active smoking cessation related Twitter accounts (N=18) were
      identified. Their 50 most recent tweets were content coded using a schema adapted
      from the Roter Interaction Analysis System (RIAS), a theory-based, validated
      coding method. Using negative binomial regression, the association of number of
      followers and frequency of individual tweet content at baseline was assessed. The
      difference in followership at 6 months (compared to baseline) to the frequency of
      tweet content was compared using linear regression. Both analyses were adjusted
      by account type (organizational or not organizational). RESULTS: The 18 accounts
      had 60,609 followers at baseline and 68,167 at 6 months. A total of 24% of tweets
      were socioemotional support (mean 11.8, SD 9.8), 14% (mean 7, SD 8.4) were
      encouraging/engagement, and 62% (mean 31.2, SD 15.2) were informational. At
      baseline, higher frequency of socioemotional support and encouraging/engaging
      tweets was significantly associated with higher number of followers
      (socioemotional: incident rate ratio [IRR] 1.09, 95% CI 1.02-1.20;
      encouraging/engaging: IRR 1.06, 95% CI 1.00-1.12). Conversely, higher frequency
      of informational tweets was significantly associated with lower number of
      followers (IRR 0.95, 95% CI 0.92-0.98). At 6 months, for every increase by 1 in
      socioemotional tweets, the change in followership significantly increased by
      43.94 (P=.027); the association was slightly attenuated after adjusting by
      account type and was not significant (P=.064). CONCLUSIONS: Smoking cessation
      activity does exist on Twitter. Preliminary findings suggest that certain content
      strategies can be used to encourage followership, and this needs to be further
      investigated.

PMID- 25589010
TI  - Temperate bacteriophages collected by outer membrane vesicles in Komagataeibacter
      intermedius.
AB  - The acetic acid bacteria have mainly relevance for bacterial cellulose production
      and fermented bio-products manufacture. The purpose of this study was to identify
      temperate bacteriophages in a cellulose-producing bacterial strain
      Komagataeibacter intermedius IMBG180. Prophages from K. intermedius IMBG180 were
      induced with mitomycin C and nalidixic acid. Transmission electron microscopy
      analysis exhibited tailed bacteriophages belonging to Myoviridae. A PCR assay
      targeting the capsid gene of the myoviruses proved phylogenetic position of
      induced phages. Nalidixic acid was poor inducer of prophages, however, it induced
      the OMV-like particles release. Size of OMVs depended on an antibiotic applied
      for phage induction and varied in the range of 30-80 and 120-200 nm. Inside some
      of them, tails of phages have been visible. Under conditions, inducing prophages,
      OMVs acted as the collectors of formed phage particles, using outer membrane
      receptors for phage detection (in this case, outer membrane siderophore
      receptor), and fulfilled therefore "a cleaning," as well as defensive functions,
      preventing bacteriophage spread outside population. This is the first description
      of myoviruses affiliated to K. intermedius, as well as outer membrane vesicles
      interaction with phages within this host. 

PMID- 25589011
TI  - How much is too much? Threshold dose distributions for 5 food allergens.
AB  - BACKGROUND: Precautionary labeling is used to warn consumers of the presence of
      unintended allergens, but the lack of agreed allergen thresholds can result in
      confusion and risk taking by patients with food allergy. The lack of data on
      threshold doses below which subjects are unlikely to react is preventing the
      development of evidence-based allergen management strategies that are understood
      by clinician and patient alike. OBJECTIVE: We sought to define threshold dose
      distributions for 5 major allergenic foods in the European population. METHODS:
      Patients with food allergy were drawn from the EuroPrevall birth cohort,
      community surveys, and outpatient clinic studies and invited to undergo a food
      challenge. Low-dose, double-blind, placebo-controlled food challenges were
      undertaken with commercially available food ingredients (peanut, hazelnut,
      celery, fish, and shrimp) blinded into common matrices. Dose distributions were
      modeled by using interval-censoring survival analysis with 3 parametric
      approaches. RESULTS: Of the 5 foods used for challenge, 4 produced similar dose
      distributions, with estimated doses eliciting reactions in 10% of the allergic
      population (ED10), ranging from 1.6 to 10.1 mg of protein for hazelnut, peanut,
      and celery with overlapping 95% CIs. ED10 values for fish were somewhat higher
      (27.3 mg of protein), although the CIs were wide and overlapping between fish and
      plant foods. Shrimp provided radically different dose distributions, with an ED10
      value of 2.5 g of protein. CONCLUSION: This evidence base will contribute to the
      development of reference doses and action levels for allergens in foods below
      which only the most sensitive subjects might react.

PMID- 25589012
TI  - Synthesis and characterization of the anticancer and metal binding properties of
      novel pyrimidinylhydrazone derivatives.
AB  - Three novel pyrimidinylhydrazones substituted at either the aromatic moiety or at
      the imine carbon atom were synthesized and characterized by standard analytical
      methods. All compounds were found to be toxic in the micro- to submicromolar
      range against a diverse panel of cancer cell lines including multidrug resistant
      (MDR) derivatives expressing P-glycoprotein (Pgp). UV-visible spectrophotometry
      experiments demonstrated that the most active compound (3) forms highly stable
      complexes with iron(III) and copper(II) in a wide pH range with a stronger
      preference towards iron(III). The redox activity of the iron and copper complexes
      of ligand 3 was investigated using cyclic voltammetry and was tested with
      cellular reductants. The impact of reactive oxygen species (ROS) on the mechanism
      of toxicity was assessed using the ROS-sensitive cell permeable dye 2',7'
      dichlorofluorescin diacetate (DCFDA). Our results demonstrate that the studied
      pyrimidinylhydrazones form redox-active iron and copper complexes that are
      capable of producing intracellular ROS, which might lead to cellular damage and
      cell death in cancer cells regardless of their resistance status. 

PMID- 25589013
TI  - Regulation of nonclassical renin-angiotensin system receptor gene expression in
      the adrenal medulla by acute and repeated immobilization stress.
AB  - The involvement of the nonclassical renin-angiotensin system (RAS) in the
      adrenomedullary response to stress is unclear. Therefore, we examined basal and
      immobilization stress (IMO)-triggered changes in gene expression of the classical
      and nonclassical RAS receptors in the rat adrenal medulla, specifically the
      angiotensin II type 2 (AT2) and type 4 (AT4) receptors, (pro)renin receptor
      [(P)RR], and Mas receptor (MasR). All RAS receptors were identified, with AT2
      receptor mRNA levels being the most abundant, followed by the (P)RR, AT1A
      receptor, AT4 receptor, and MasR. Following a single IMO, AT2 and AT4 receptor
      mRNA levels decreased by 90 and 50%, respectively. Their mRNA levels were also
      transiently decreased by repeated IMO. MasR mRNA levels displayed a 75% transient
      decrease as well. Conversely, (P)RR mRNA levels were increased by 50% following
      single or repeated IMO. Because of its abundance, the function of the (P)RR was
      explored in PC-12 cells. Prorenin activation of the (P)RR increased
      phosphorylation of extracellular signal-regulated kinase 1/2 and tyrosine
      hydroxylase at Ser(31), likely increasing its enzymatic activity and
      catecholamine biosynthesis. Together, the broad and dynamic changes in gene
      expression of the nonclassical RAS receptors implicate their role in the
      intricate response of the adrenomedullary catecholaminergic system to stress.

PMID- 25589014
TI  - A cholinergic contribution to the circulatory responses evoked at the onset of
      handgrip exercise in humans.
AB  - A cholinergic (muscarinic) contribution to the initial circulatory response to
      exercise in humans remains controversial. Herein, we posit that this may be due
      to exercise mode with a cholinergic contribution being important during isometric
      handgrip exercise, where the hyperemic response of the muscle is relatively small
      compared with the onset of leg cycling, where a marked increase in muscle blood
      flow rapidly occurs as a consequence of multiple redundant mechanisms. We
      recorded blood pressure (BP; brachial artery), stroke volume (pulse contour
      analysis), cardiac output, and systemic vascular resistance (SVR) in young
      healthy males, while performing either 20 s of isometric handgrip contraction at
      40% maximum voluntary contraction (protocol 1; n = 9) or 20 s of low-intensity
      leg cycling exercise (protocol 2; n = 8, 42 +/- 8 W). Exercise trials were
      conducted under control (no drug) conditions and following cholinergic blockade
      (glycopyrrolate). Under control conditions, isometric handgrip elicited an
      initial increase in BP (+5 +/- 2 mmHg at 3 s and +3 +/- 1 mmHg at 10 s, P <
      0.05), while SVR dropped after 3 s (-27 +/- 6% at 20 s; P < 0.05). Cholinergic
      blockade abolished the isometric handgrip-induced fall in SVR and, thereby,
      augmented the pressor response (+13 +/- 3 mmHg at 10 s; P < 0.05 vs. control). In
      contrast, cholinergic blockade had a nonsignificant effect on changes in BP and
      SVR at the onset of leg cycling exercise. These findings suggest that a
      cholinergic mechanism is important for the BP and SVR responses at the onset of
      isometric handgrip exercise in humans.

PMID- 25589015
TI  - Using ecology to inform physiology studies: implications of high population
      density in the laboratory.
AB  - Conspecific density is widely recognized as an important ecological factor across
      the animal kingdom; however, the physiological impacts are less thoroughly
      described. In fact, population density is rarely mentioned as a factor in
      physiological studies on captive animals and, when it is infrequently addressed,
      the animals used are reared and housed at densities far above those in nature,
      making the translation of results from the laboratory to natural systems
      difficult. We survey the literature to highlight this important ecophysiological
      gap and bring attention to the possibility that conspecific density prior to
      experimentation may be a critical factor influencing results. Across three taxa:
      mammals, birds, and fish, we present evidence from ecology that density
      influences glucocorticoid levels, immune function, and body condition with the
      intention of stimulating discussion and increasing consideration of population
      density in physiology studies. We conclude with several directives to improve the
      applicability of insights gained in the laboratory to organisms in the natural
      environment.

PMID- 25589016
TI  - Hemorrhagic hypotension-induced hypersensitivity of vagal pulmonary C-fibers to
      chemical stimulation and lung inflation in anesthetized rats.
AB  - This study was carried out to investigate whether hemorrhagic hypotension (HH)
      altered the sensitivity of vagal pulmonary C-fibers. The fiber activity (FA) of
      single vagal pulmonary C-fiber was continuously recorded in anesthetized rats
      before, during, and after HH was induced by bleeding from the femoral arterial
      catheter into a blood reservoir and lowering the mean systemic arterial pressure
      (MSAP) to ~40 mmHg for 20 min. Our results showed the following. First, after
      MSAP reached a steady state of HH, the peak FA response to intravenous injection
      of capsaicin was elevated by approximately fivefold. The enhanced C-fiber
      sensitivity continued to increase during HH and sustained even after MSAP
      returned to baseline during the recovery, but slowly returned to control ~20 min
      later. Second, responses of FA to intravenous injections of other chemical
      stimulants of pulmonary C-fibers (phenylbiguanide, lactic acid, and adenosine)
      and a constant-pressure lung hyperinflation were all significantly potentiated by
      HH. Third, infusion of sodium bicarbonate alleviated the systemic acidosis during
      HH, and it also attenuated, but did not completely prevent, the HH-induced C
      fiber hypersensitivity. In conclusion, the pulmonary C-fiber sensitivity was
      elevated during HH, probably caused by the endogenous release of chemical
      substances (e.g., lactic acid) that were produced by tissue ischemia during HH.
      This enhanced C-fiber sensitivity may heighten the pulmonary protective reflexes
      mediated through these afferents (e.g., cough, J reflex) during hemorrhage when
      the body is more susceptible to other hazardous insults and pathophysiological
      stresses.

PMID- 25589017
TI  - Incidence of Gallstone Formation and Cholecystectomy 10 Years After Bariatric
      Surgery.
AB  - PURPOSE: Rapid weight loss is a risk factor for gallstone formation, and
      postoperative treatment options for gallstone formation are still part of
      scientific discussion. No prospective studies monitored the incidence for
      gallstone formation and subsequent cholecystectomy after bariatric surgery longer
      than 5 years. The aim of the study was to determine the incidence of gallstone
      formation and cholecystectomy in bariatric patients over 10 years. MATERIALS AND
      METHODS: One hundred nine patients were observed over 10 years after laparoscopic
      gastric banding or gastric bypass/gastric sleeve. The incidence of gallstone
      formation and cholecystectomy was correlated to longitudinal changes in
      anthropometric parameters. RESULTS: In total, 91 female and 18 male patients were
      examined. Nineteen patients had postoperative gallstone formation, and 12 female
      patients required cholecystectomy. The number needed to harm for gallstone
      formation was 7.1 and 2.3 cases in the banding group and gastric bypass/gastric
      sleeve group, respectively. The number needed to harm for cholecystectomy was
      11.6 and 2.5 cases in the banding group and the gastric bypass/gastric sleeve
      group, respectively. Weight loss was higher in patients requiring subsequent
      cholecystectomy. Mean follow-up to cholecystectomy was 21.5 months with the
      latest operation after 51 months. CONCLUSION: Female gender and rapid weight loss
      were major risk factors for postoperative cholelithiasis. Ultrasound examinations
      within 2 to 5 years are recommended in every patient, independent of bariatric
      procedure. Pharmacologic treatment should be considered in high risk patients
      within 2 to 5 years to prevent postoperative cholelithiasis. This helps to
      optimize patient care and lowers postoperative morbidity.

PMID- 25589018
TI  - Mood disorders are highly prevalent but underdiagnosed among patients seeking
      bariatric surgery.

PMID- 25589019
TI  - Outcome of leaks after sleeve gastrectomy based on a new algorithm adressing leak
      size and gastric stenosis.
AB  - BACKGROUND: Leaks after laparoscopic sleeve gastrectomy (LSG) are estimated to be
      the most serious complication of this procedure due to difficult healing process
      using non-standardized endoscopic approaches. Initially, endoscopic management
      recommended the use of stents. METHODS: A total of 19 patients received
      endoscopic treatment after LSG to manage leaks. The leak was classified depending
      on the primary orifice's size (more or less than 10 mm) or on the presence of
      gastric stenosis. The primary aim was to develop a therapeutic algorithm in order
      to reduce the number of endoscopic procedures. RESULTS: The average number of
      endoscopic procedures was 2.8 (range 2-5) in group A (leak size <10 mm) and 4
      (range 3-7) in group B (leak size >10 mm). Two out of 13 patients had stent
      migration (15.4 %) and required an additional procedure, one in group A and
      another in group B. The average duration to achieve complete healing was 3.4
      months (range 2-14 months), 2.8 months for group A and 3.9 months for group B.
      CONCLUSIONS: Limited data can be found in the literature on leaks after LSG. A
      new algorithm based on leak size permits standardization of endoscopic management
      and reduces procedures after LSG.

PMID- 25589020
TI  - Clinical effectiveness of exenatide in diabetic patients waiting for bariatric
      surgery.
AB  - BACKGROUND: Bariatric surgery constitutes the most effective treatment for
      severely obese type 2 diabetic patients. Exenatide is a glucagon-like peptide 1
      receptor agonist that can improve glycemic control and cause weight loss in
      patients with type 2 diabetes. Clinical experience with exenatide in obese
      patients with type 2 diabetes waiting for bariatric surgery has not been
      reported. The aim of the study was to evaluate, in clinical practice, weight and
      metabolic effects of exenatide (after 3 and 6 months) in patients with type 2
      diabetes and obesity waiting for bariatric surgery. METHODS: A total of 100
      diabetic adult subjects with a BMI >= 35 kg/m(2) were included. Primary endpoints
      were changes in weight and HbA1c after 6 months of treatment. Secondary endpoints
      were changes from baseline of a variety of clinical measures (triglycerides
      levels, blood pressure, and waist circumference). Data were analyzed at 3 and 6
      months of follow-up. RESULTS: Treatment for 6 months with exenatide decreased
      significantly body weight (-12.5 kg) and waist circumference (-13 cm). Twenty
      percent of patients reduced their BMI under 35 kg/m(2) and significantly improved
      their metabolic profile (HbA1c <7 %). Significant and maintained decreases in
      HbA1c of 1 % were observed in the 3 and 6 months cohorts. Triglycerides levels
      and blood pressure also decreased from baseline to the end of the study.
      Treatment was discontinued in 19 % of patients mainly due to drug inefficacy (6
      %) or adverse events (4 %). CONCLUSIONS: Exenatide twice daily (BID) leads to
      early, robust, and significant weight loss in a subset of patients with diabetes
      and severe obesity before bariatric surgery. Clinical trials are needed to
      confirm the benefits of GLP-1 agonists in type 2 diabetic obese patients or high
      risk super-obese patients waiting for bariatric surgery.

PMID- 25589021
TI  - External focus and autonomy support: two important factors in motor learning have
      additive benefits.
AB  - We examined whether the combination of two factors that have consistently been
      found to enhance motor learning - an external focus (EF) of attention and
      autonomy support (AS) - would produce additive benefits. Participants practiced
      throwing with their non-dominant arm. In a 2*2 design, they were or were not
      asked to focus externally (i.e., on the target), and were or were not given a
      choice (autonomy support). The latter involved choosing 2 5-trials blocks during
      practice on which they used their dominant arm. All four groups - EF/AS, EF, AS,
      and C (control) - completed a practice phase consisting of 60 trials. The
      distance to the target (bull's eye) was 7.5m. One day later, participants
      performed retention (same target distance) and transfer tests (8.5m). Both
      external focus instructions and autonomy support enhanced retention and transfer
      performance. Importantly, the combination of these factors resulted in additive
      learning advantages. The EF/AS group showed the greatest throwing accuracy, and
      the EF and AS groups outperformed the C group. In addition, self-efficacy
      measured after practice and before retention and transfer was increased by both
      factors. Thus, promoting an external focus of attention and supporting learners'
      need for autonomy seem to independently influence learning.

PMID- 25589023
TI  - Optical nanoparticles: general discussion.

PMID- 25589022
TI  - Upgrading Preschool Environment in a Swedish Municipality: Evaluation of an
      Implementation Process.
AB  - Redesigning outdoor preschool environment may favorably affect multiple factors
      relevant to health and reach many children. Cross-sectional studies in various
      landscapes at different latitudes have explored the characteristics of preschool
      outdoor environment considering the play potential triggering combined physical
      activity and sun-protective behavior due to space, vegetation, and topography.
      Criteria were pinpointed to upgrade preschool outdoor environment for multiple
      health outcomes to be applied in local government in charge of public preschools.
      Purposeful land use policies and administrative management of outdoor land use
      may serve to monitor the quality of preschool outdoor environments (upgrading and
      planning). This study evaluates the process of implementing routines for
      upgrading outdoor preschool environments in a medium-sized municipality, Sweden,
      2008-2011, using qualitative and quantitative analysis. Recorded written material
      (logs and protocols) related to the project was processed using thematic
      analysis. Quantitative data (m(2) flat/multileveled, overgrown/naked surface, and
      fraction of free visible sky) were analyzed to assess the impact of
      implementation (surface, topography, greenery integrated in play). The preschool
      outdoor environments were upgraded accordingly. The quality of implementation was
      assessed using the theory of policy streams approach. Though long-term impact
      remains to be confirmed the process seems to have changed work routines in the
      interior management for purposeful upgrading of preschool outdoor environments.
      The aptitude and applicability of inexpensive methods for assessing, selecting,
      and upgrading preschool land at various latitudes, climates, and outdoor play
      policies (including gender aspects and staff policies) should be further
      discussed, as well as the compilation of data for monitoring and evaluation. 

PMID- 25589024
TI  - Semi-automatic organelle detection on transmission electron microscopic images.
AB  - Recent advances in the acquisition of large-scale datasets of transmission
      electron microscope images have allowed researchers to determine the number and
      the distribution of subcellular ultrastructures at both the cellular level and
      the tissue level. For this purpose, it would be very useful to have a computer
      assisted system to detect the structures of interest, such as organelles. Using
      our original image recognition framework CARTA (Clustering-Aided Rapid Training
      Agent), combined with procedures to highlight and enlarge regions of interest on
      the image, we have developed a successful method for the semi-automatic detection
      of plant organelles including mitochondria, amyloplasts, chloroplasts,
      etioplasts, and Golgi stacks in transmission electron microscope images. Our
      proposed semi-automatic detection system will be helpful for labelling organelles
      in the interpretation and/or quantitative analysis of large-scale electron
      microscope imaging data. 

PMID- 25589025
TI  - [Surgery for male urinary incontinence: where are we now and what is in the
      pipeline?].
AB  - Male stress urinary incontinence, which has radical prostatectomy as the main
      aetiology, affects about 39% of the adult male population and is one of the
      complications of radical prostatectomy with the greatest impact on the quality of
      life of patients. There are a wide range of treatments for stress urinary
      incontinence available to the urologist, ranging from conservative treatments to
      surgical treatments, from minimally invasive procedures to the implant of
      artificial sphincter prosthesis. The aim of this work is to define the state-of
      the-art of surgical treatments for male stress urinary incontinence, analyzing
      the most recent studies in the literature and evaluating the available scientific
      evidence. 

PMID- 25589026
TI  - Robotic-assisted partial nephrectomy: experience on 60 cases.
AB  - INTRODUCTION: Laparoscopic partial nephrectomy is still one of the more
      challenging procedures in urology. Minimizing warm ischemia time (WIT) and
      bleeding requires efficient intracorporeal suturing. In addition, achieving
      negative surgical margins requires complete excision of the tumor. Robotic
      assisted partial nephrectomy (RALPN) adds the advantages offered by the "Da Vinci
      system" to laparoscopy, such as the 3-D vision, and the better degree of freedom
      of surgical instruments. OBJECTIVE: The objective of this study is to report our
      experience with RALPN. METHODS: From August 2009 to October 2012, 60 patients
      underwent RALPN for kidney cancer. The average age of the patients (35 female, 25
      male) was 63 (range 48-80) years. Average BMI was 25 (range 21.8-29.7) kg/m2.
      Average tumor size was 3.2 cm (range 2-6.7 cm). All the procedures were performed
      by a transperitoneal approach. Ilar clamping was used in all cases: in 47
      patients by one intracorporeal tourniquet for the artery and one for the vein; in
      three cases, ilar clamping was "en block" by Satinsky. RESULTS: Mean operative
      time was 167.2 min (140-250) with a WIT of 23.8 min (15-28). The mean estimated
      blood loss was 260 mL (50-300). In one case, nephrectomy was necessary because
      the tumor involved the renal pedicle. One patient had pulmonary embolism and one
      urinary leakage conservatively managed.Pathologic examination revealed clear cell
      renal cell carcinoma in 58 patients, oncocytoma in one patient, and
      angiomyolipoma in one patient. All resection margins were free from tumor.
      CONCLUSIONS: Partial nephrectomy, facilitated by robotic technology, is more and
      more frequently performed as a safe and effective minimally invasive procedure.

PMID- 25589027
TI  - Endourethral migration of a Hem-o-Lok Clip after robot-assisted laparoscopic
      radical prostatectomy.
AB  - Hem-o-Lok clips (Weck Surgical Instruments, Teleflex Medical, Durham, North
      Carolina, USA) are widely used in robot-assisted laparoscopic radical
      prostatectomy because of their easy application and secure clamping. To date,
      there have been some reports of their migration into the urinary tract, causing
      urethral erosion, bladder neck contractures orcalculus formation. We report a
      case of endourethral migration of a hem-o-lok after robot-assisted laparoscopic
      prostatectomy. The hem-o-lok was almost completely endoluminal and attached to
      one end at the vesico-urethral anastomosis. The hem-o-lok was easily removed
      cystoscopically by using an endoscopic forceps. 

PMID- 25589028
TI  - [Female incontinence surgery: state of the art].
AB  - Female urinary incontinence represents a medical and social problem with huge
      impact regarding both patient's quality of life and social costs. The diagnosis
      is important for therapeutic choice and should consider some factors: the degree
      of urethral mobility, urodynamics parameters, patient's will and expectations,
      information about surgical complications and risks. Nowadays suburethral sling
      evolution and bulking therapy for selected cases consent to perform miniinvasive
      surgery; the most relevant problem concerns the management of postoperative
      complications: in this sense autologous slings are used after urethrolisis. In
      most difficult cases, it is possible to consider artificial sphincter as the best
      option. 

PMID- 25589029
TI  - Urinary incontinence and neuropathy after radical prostatectomy: diagnosis and
      treatment.
AB  - INTRODUCTION AND OBJECTIVE: The urinary incontinence after radical prostatectomy
      is secondary to neuropathy with various degrees from neurapraxia to neurotmesis.
      We propose to apply therapeutic and rehabilitative models appropriate to the
      diagnosis and to evaluate the results. MATERIALS AND METHODS: We examined 79
      homogeneous patients with urinary incontinence after radical prostatectomy. After
      having defined the diagnosis by a urodynamic examination, the study of pudendal
      nerve somatosensory-evoked potentials (SEPs) and perineal electromyography (EMG),
      patients were divided into four groups (A; B; C; D) and submitted to different
      clinical drug protocols and rehabilitation. After 3 months, patients were
      reevaluated. RESULTS: Twenty-eight patients with idiopathic overactive bladder
      (Group A) have been treated with anticholinergics: two unchanged (7%); 14
      improved (50%); and 12 recovered (43%). Sixteen patients with overactive bladder
      and sphincter incompetence (Group B) have practiced physiokinesis therapy (FKT)
      of pelvic floor and anticholinergic therapy: one unchanged (6%); eight improved
      (50%); and seven recovered (44%). Fourteen patients with perineal incompetence to
      continence (Group C) have been treated with FES, FKT of pelvic floor, and
      Biofeedback: three patients were unchanged (21%); five improved (36%); and six
      recovered (43%). Twenty-one patients with sphincter denervation (Group D)
      performed FES, FKT of pelvic floor, and Biofeedback: 16 unchanged (76%); five
      improved (24%); and zero recovered (0%). Of these 16 patients, six non-responders
      have placed a transobturator tape (TOT) sling and four an artificial sphincter.
      CONCLUSIONS: A therapy adherent to the diagnosis increases success rate.

PMID- 25589030
TI  - Association of Concurrent fNIRS and EEG Signatures in Response to Auditory and
      Visual Stimuli.
AB  - Functional near-infrared spectroscopy (fNIRS) has been proven reliable for
      investigation of low-level visual processing in both infants and adults. Similar
      investigation of fundamental auditory processes with fNIRS, however, remains only
      partially complete. Here we employed a systematic three-level validation approach
      to investigate whether fNIRS could capture fundamental aspects of bottom-up
      acoustic processing. We performed a simultaneous fNIRS-EEG experiment with visual
      and auditory stimulation in 24 participants, which allowed the relationship
      between changes in neural activity and hemoglobin concentrations to be studied.
      In the first level, the fNIRS results showed a clear distinction between visual
      and auditory sensory modalities. Specifically, the results demonstrated area
      specificity, that is, maximal fNIRS responses in visual and auditory areas for
      the visual and auditory stimuli respectively, and stimulus selectivity, whereby
      the visual and auditory areas responded mainly toward their respective stimuli.
      In the second level, a stimulus-dependent modulation of the fNIRS signal was
      observed in the visual area, as well as a loudness modulation in the auditory
      area. Finally in the last level, we observed significant correlations between
      simultaneously-recorded visual evoked potentials and deoxygenated hemoglobin
      (DeoxyHb) concentration, and between late auditory evoked potentials and
      oxygenated hemoglobin (OxyHb) concentration. In sum, these results suggest good
      sensitivity of fNIRS to low-level sensory processing in both the visual and the
      auditory domain, and provide further evidence of the neurovascular coupling
      between hemoglobin concentration changes and non-invasive brain electrical
      activity. 

PMID- 25589031
TI  - The effect of unemployment on self-reported health and mental health in Greece
      from 2008 to 2013: a longitudinal study before and during the financial crisis.
AB  - The current study uses six annual waves of the Longitudinal Labor Market Study
      (LLMS) covering the 2008-2013 period to obtain longitudinal estimations
      suggesting statistically significant negative effects from unemployment on self
      reported health and mental health in Greece. The specifications suggest that
      unemployment results in lower health and the deterioration of mental health
      during the 2008-2009 period compared with the 2010-2013 period, i.e., a period in
      which the country's unemployment doubled as a consequence of the financial
      crisis. Unemployment seems to be more detrimental to health/mental health in
      periods of high unemployment, suggesting that the unemployment crisis in Greece
      is more devastating as it concerns more people. Importantly, in all
      specifications, comparable qualitative patterns are found by controlling for
      unemployment due to firm closure, which allows us to minimize potential bias due
      to unemployment-health related reverse causality. Moreover, in all cases, women
      are more negatively affected by unemployment in relation to their health and
      mental health statuses than are men. Greece has been more deeply affected by the
      financial crisis than any other EU country, and this study contributes by
      offering estimates for before and during the financial crisis and considering
      causality issues. Because health and mental health indicators increase more
      rapidly in a context of higher surrounding unemployment, policy action must place
      greater emphasis on unemployment reduction and supporting women's employment. 

PMID- 25589032
TI  - Attitudes towards legalising physician provided euthanasia in Britain: the role
      of religion over time.
AB  - Hastening the death of another whether through assisted suicide or euthanasia is
      the subject of intense debate in the UK and elsewhere. In this paper we use a
      nationally representative survey of public attitudes - the British Social
      Attitudes survey - to examine changes in attitudes to the legalisation of
      physician provided euthanasia (PPE) over almost 30 years (1983-2012) and the role
      of religious beliefs and religiosity in attitudes over time. Compatible questions
      about attitudes to euthanasia were available in the six years of 1983, 1984,
      1989, 1994, 2005, and 2012. We study the trends in the support for legalisation
      through these time points and the relationship between attitudes, religious
      denomination and religiosity, controlling for a series of covariates. In total,
      8099 individuals provided answers to the question about PPE in the six years of
      the study. The support for legalisation rose from around 76.95% in 1983 to 83.86%
      in 2012. This coincided with an increase in secularisation exhibited in the
      survey: the percentage of people with no religious affiliation increasing from
      31% to 45.4% and those who do not attend a religious institution (e.g. church)
      increasing from 55.7% to 65.03%. The multivariate analysis demonstrates that
      religious affiliation and religiosity as measured by religious institution
      attendance frequency are the main contributors to attitudes towards euthanasia,
      and that the main increase in support happened among the group with least
      religious affiliation. Other socio-demographic characteristics do not seem to
      alter these attitudes systematically across the years. Our study demonstrates an
      increase in the support of euthanasia legalisation in Britain in the last 30
      years coincided with increased secularisation. It does not follow, however, that
      trends in public support are immutable nor that a change in the law would improve
      on the current pragmatic approach toward hastening death by a physician adopted
      in England and Wales in terms of the balance between compassion and safeguards
      against abuse offered. 

PMID- 25589033
TI  - Examining individual and school characteristics associated with child obesity
      using a multilevel growth model.
AB  - The childhood obesity epidemic continues to be a serious concern in the U.S.,
      disproportionately affecting low socioeconomic and minority groups. Because many
      interventions are based in schools, both individual and school factors
      contributing to obesity were examined in this study. Employing data from the
      Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999 (ECLS-K), a
      three level hierarchical linear model was used to estimate children's body mass
      index (BMI) growth trajectories within their school contexts. Results indicated
      an inverse relationship between BMI and socioeconomic status (SES), except for
      black males. Additionally, results showed that low school SES and rural locality
      of the school were school-level risk factors of obesity. Lastly, a major portion
      of the between-schools variance was explained by aggregated student
      characteristics, indicating that students were more likely to attend schools with
      peers of similar BMI who had similar SES and race/ethnicity, supporting a school
      level compositional effect associated with obesity. 

PMID- 25589034
TI  - Ethnic discrimination predicts poor self-rated health and cortisol in pregnancy:
      insights from New Zealand.
AB  - Despite growing research emphasis on understanding the health effects of ethnic
      discrimination, little work has focused on how such exposures may influence a
      woman's biology and health during pregnancy. Understanding such effects is
      important given evidence that maternal stress experience in pregnancy can have
      long term effects on offspring health. Here we present data evaluating the
      relationship between perceived discrimination, self-rated health, and the stress
      hormone cortisol measured in late pregnancy among a diverse sample of women
      living in Auckland, New Zealand (N = 55). We also evaluated possible
      intergenerational impacts of maternal discrimination on stress reactivity in a
      subset of offspring (N = 19). Pregnant women were recruited from two antenatal
      care clinics in Auckland. Women were met in their homes between 34 and 36 weeks
      gestation, during which time a prenatal stress questionnaire was administered and
      saliva samples (morning and evening from two days) were obtained. Offspring
      cortisol reactivity was assessed at the standard six week postnatal vaccination
      visit. We found that 34% of women reported having experienced ethnic
      discrimination, with minority and immigrant women being more likely to report
      being angry or upset in response to discrimination experience compared with NZ
      born women of European descent. Women reporting discrimination experience had
      worse self-rated health, higher evening cortisol and gave birth to infants with
      higher cortisol reactivity, all independent of ethnicity and material
      deprivation. These findings suggest that discrimination experience can have
      biological impacts in pregnancy and across generations, potentially contributing
      to the ethnic gradient in health.

PMID- 25589035
TI  - Psychiatrists' Perceptions of Role-Playing Games.
AB  - The literature has seen a surge in research on the mental health impacts of
      technologies such as Facebook, video games, and massively-multiplayer online role
      playing games such as World of Warcraft, but little is known regarding the mental
      health impact of non-video role-playing games, such as Dungeons & Dragons. The
      present study examines how psychiatrists' perceive role-playing games and whether
      they play them. Psychiatrists at a tertiary care centre in Canada completed a
      questionnaire assessing history of playing role-playing games and whether they
      associate them with psychopathology. Forty-eight psychiatrists responded. Twenty
      three percent have played a role-playing game over their lifetimes. Twenty-two
      percent believed there was an association between psychopathology and role
      playing games. A majority of psychiatrists who responded do not associate role
      playing games with psychopathology. Implications for clinical practice and future
      research are discussed. 

PMID- 25589036
TI  - Confinement without boundaries: anisotropic diffusion on the surface of a
      cylinder.
AB  - Densely packed systems of thermal particles in curved geometries are frequently
      encountered in biological and microfluidic systems. In 2D systems, at
      sufficiently high surface coverage, diffusive motion is widely known to be
      strongly affected by physical confinement, e.g., by the walls. In this work, we
      explore the effects of confinement by shape, not rigid boundaries, on the
      diffusion of discs by confining them to the surface of a cylinder. We find that
      both the magnitude and the directionality of lateral diffusion is strongly
      influenced by the radius of the cylinder. An anisotropy between diffusion in the
      longitudinal and circumferential direction of the cylinder develops. We
      demonstrate that the origin of this effect lies in the fact that screw-like
      packings of mono- and oligodisperse discs on the surface of a cylinder induce
      preferential collective motions in the circumferential direction, but also show
      that even in polydisperse systems lacking such order an intrinsic finite size
      confinement effect increases diffusivity in the circumferential direction. 

PMID- 25589037
TI  - Deaths after Fluad flu vaccine and the epidemic of panic in Italy.

PMID- 25589038
TI  - Ultrafast room-temperature crystallization of TiO2 nanotubes exploiting water
      vapor treatment.
AB  - In this manuscript a near-room temperature crystallization process of anodic
      nanotubes from amorphous TiO2 to anatase phase with a fast 30 minutes treatment
      is reported for the first time. This method involves the exposure of as-grown
      TiO2 nanotubes to water vapor flow in ambient atmosphere. The water vapor
      crystallized samples are deeply investigated in order to gain a whole
      understanding of their structural, physical and chemical properties. The
      photocatalytic activity of the converted material is tested by dye degradation
      experiment and the obtained performance confirms the highly promising properties
      of this low-temperature processed material. 

PMID- 25589039
TI  - How should the legal framework for the protection of human genomic data be
      formulated?-Implications from the revision processes of the Act on the Protection
      of Personal Information (PPI Act).

PMID- 25589041
TI  - Agnathia-otocephaly complex and asymmetric velopharyngeal insufficiency due to an
      in-frame duplication in OTX2.
AB  - Agnathia-otocephaly complex is a malformation characterized by absent/hypoplastic
      mandible and abnormally positioned ears. Mutations in two genes, PRRX1 and OTX2,
      have been described in a small number of families with this disorder. We
      performed clinical and genetic testing in an additional family. The proband is a
      healthy female with a complicated pregnancy history that includes two offspring
      diagnosed with agnathia-otocephaly during prenatal ultrasound scans. Exome
      sequencing was performed in fetal DNA from one of these two offspring revealing a
      heterozygous duplication in OTX2: c.271_273dupCAG, p.(Gln91dup). This change
      leads to the insertion of a glutamine within the OTX2 homeodomain region, and is
      predicted to alter this signaling molecule's ability to interact with DNA. The
      same variant was also identified in the proband's clinically unaffected 38-year
      old husband and their 9-year-old daughter, who presented with a small mandible,
      normal ears and velopharyngeal insufficiency due to a short hemi-palate. This
      unusual presentation of OTX2-related disease suggests that OTX2 might have a role
      in palatal hypoplasia cases. A previously unreported OTX2 variant associated with
      extreme intrafamilial variability is described and the utility of exome
      sequencing as a tool to confirm the diagnosis of agnathia-otocephaly and to
      inform the reproductive decisions of affected families is highlighted. 

PMID- 25589042
TI  - A reply to a commentary on identification of the rare compound heterozygous
      variants in the NEB gene in a Korean family with intellectual disability,
      epilepsy and early-childhood-onset generalized muscle weakness.

PMID- 25589040
TI  - Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal
      dominant nonsyndromic hearing loss DFNA4B in a Chinese family.
AB  - Autosomal dominant nonsyndromic hearing loss (ADNSHL/DFNA) is a highly
      genetically heterogeneous disorder. Hitherto only about 30 ADNSHL-causing genes
      have been identified and many unknown genes remain to be discovered. In this
      research, genome-wide linkage analysis mapped the disease locus to a 4.3 Mb
      region on chromosome 19q13 in SY-026, a five-generation nonconsanguineous Chinese
      family affected by late-onset and progressive ADNSHL. This linkage region showed
      partial overlap with the previously reported DFNA4. Simultaneously, probands were
      analyzed using exome capture followed by next-generation sequencing.
      Encouragingly, a heterozygous missense mutation, c.505G>A (p.G169R) in exon 3 of
      the CEACAM16 gene (carcinoembryonic antigen-related cell adhesion molecule 16),
      was identified via this combined strategy. Sanger sequencing verified that the
      mutation co-segregated with hearing loss in the family and that it was not
      present in 200 unrelated control subjects with matched ancestry. This is the
      second report in the literature of a family with ADNSHL caused by CEACAM16
      mutation. Immunofluorescence staining and western blots also prove CEACAM16 to be
      a secreted protein. Furthermore, our studies in transfected HEK293T cells show
      that the secretion efficacy of the mutant CEACAM16 is much lower than that of the
      wild type, suggesting a deleterious effect of the sequence variant. 

PMID- 25589043
TI  - A commentary on identification of the rare compound heterozygous variants in the
      NEB gene in a Korean family with intellectual disability, epilepsy and early
      childhood-onset generalized muscle weakness.

PMID- 25589044
TI  - Oxidative stress protection by polyphosphate--new roles for an old player.
AB  - Inorganic polyphosphate is a universally conserved biopolymer whose association
      with oxidative stress resistance has been documented in many species, but whose
      mode of action has been poorly understood. Here we review the recent discovery
      that polyphosphate functions as a protein-protective chaperone, examine the
      mechanisms by which polyphosphate-metal ion interactions reduce oxidative stress,
      and summarize polyphosphate's roles in regulating general stress response
      pathways. Given the simple chemical structure and ancient pedigree of
      polyphosphate, these diverse mechanisms are likely to be broadly relevant in many
      organisms, from bacteria to mammalian cells.

PMID- 25589046
TI  - Contact allergy to acrylates and methacrylates in consumers and nail artists -
      data of the Information Network of Departments of Dermatology, 2004-2013.
AB  - BACKGROUND: Allergic contact dermatitis caused by (meth)acrylates used in
      artificial nails is a relevant problem in both nail artists and consumers.
      OBJECTIVE: To analyse the frequency of this problem in the contact allergy
      surveillance network Information Network of Departments of Dermatology in 2004
      2013, and address possible time trends and patterns of co-sensitization. METHODS:
      A retrospective analysis of patch test results with (meth)acrylates, along with
      clinical and demographic data, was performed. These were used to subdivide
      patients according to (i) a potentially exposed occupation and (ii) nail
      cosmetics as the suspected cause of contact dermatitis. RESULTS: Among the 114
      440 patients patch tested, 72 244 were female and were considered further. Eighty
      seven patients both worked as nail artists/cosmetologists and suspected nail
      cosmetics as the cause of dermatitis. Among these, 47.1% reacted to at least one
      (meth)acrylate, most often to 2-hydroxyethyl methacrylate (n = 27), 2
      hydroxypropyl methacrylate, and hydroxyethyl acrylate (n = 26 each), with marked
      coupled reactivity. In other subgroups of interest, frequencies of sensitization
      to (meth)acrylates were less elevated but higher than in all remaining female
      patients (n = 69 419). CONCLUSIONS: The results indicate a not entirely common,
      but potentially serious, problem, especially concerning occupationally exposed,
      and sensitized, nail artists. Adequate protective measures should be taught as
      part of the vocational training.

PMID- 25589047
TI  - Role of the registered nurse in the care of the pregnant woman receiving
      analgesia and anesthesia by catheter techniques.

PMID- 25589045
TI  - Temporal and evolutionary dynamics of two-component signaling pathways.
AB  - Bacteria sense and respond to numerous environmental signals through two
      component signaling pathways. Typically, a given stimulus will activate a sensor
      histidine kinase to autophosphorylate and then phosphotransfer to a cognate
      response regulator, which can mount an appropriate response. Although these
      signaling pathways often appear to be simple switches, they can also orchestrate
      surprisingly sophisticated and complex responses. These temporal dynamics arise
      from several key regulatory features, including the bifunctionality of histidine
      kinases as well as positive and negative feedback loops. Two-component signaling
      pathways are also dynamic on evolutionary time-scales, expanding dramatically in
      many species through gene duplication and divergence. Here, we review recent work
      probing the temporal and evolutionary dynamics of two-component signaling
      systems.

PMID- 25589049
TI  - Lyme disease update for the general dermatologist.
AB  - Lyme disease is an Ixodes tick-borne illness that may arise from different
      species of the Borrelia spirochete and may be propagated in various hosts. Humans
      are considered dead-end hosts in this propagation cycle but may have a range of
      Lyme disease characteristics as a result of borrelial infection. Lyme disease has
      varied cutaneous manifestations, and the approach to diagnosis and treatment is
      based on the patient, the region, and suspected coinfection with another tick
      borne illness. An understanding of the distribution of the Ixodes tick, its
      vectors, and the most likely dermatologic presentation based on these factors
      allows the dermatologist to make appropriate testing and treatment
      recommendations. Our aim is to simplify this approach for the treating
      practitioner. 

PMID- 25589048
TI  - Synthesis and Biological Evaluation of Strictosamide Derivatives with Improved
      Antiviral and Antiproliferative Activities.
AB  - A series of novel derivatives of strictosamide were synthesized and biologically
      evaluated. Most of the new compounds exhibited improved activities than the
      parent compound strictosamide. Among them, compounds Ib and If possessed
      antiviral activities against influenza A virus (A/Jinan/15/90) with IC50 values
      of 4.12 and 12.35 MUg/mL, respectively. Compound Ie possessed antiviral activity
      against respiratory syncytial virus (RSV) with an IC50 value of 9.58 MUg/mL. Both
      compounds IIc and IId had moderate antiproliferative effects against five human
      cancer cell lines. The preliminary structure-activity relationships were also
      concluded. This study provides a promising new template with potential antiviral
      activity. 

PMID- 25589050
TI  - Clinicopathological and diagnostic characterization of confluent and reticulate
      papillomatosis of Gougerot and Carteaud: a retrospective study in a South-East
      Asian population.
AB  - BACKGROUND: Confluent and reticulate papillomatosis of Gougerot and Carteaud
      (CRP) is a rare dermatological condition, which has not been reported widely in
      Asian populations. AIM: To characterize the clinicopathological and diagnostic
      features of CRP in a South-East Asian population. METHODS: The medical records of
      29 patients accorded the diagnosis of CRP at the National Skin Centre, Singapore,
      from 1990 to 2011, were analyzed. RESULTS: The male to female ratio was 2.6:1.
      Eight patients were Indians. The mean age at the onset of skin eruptions was 29.1
      years (range 16-55 years), while the mean duration was 19.9 months (range 0.5-120
      months). CRP itself was the most common preliminary diagnosis. Fungal smears were
      negative in all 22 instances. All 29 patients had received a trial of antifungal
      therapy before being seen at our center. Antifungal therapy was repeated in three
      subjects, and the response was uniformly poor. Conversely, the treatment response
      with tetracyclines was excellent, yielding more than a 50% response in all 14
      patients. Four patients suffered recurrence of CRP. According to the diagnostic
      criteria set forth by Davis et al., 25/29 patients (86.2%) and 19/29 patients
      (65.6%) fulfilled at least three and four criteria, respectively. CONCLUSION: A
      predilection for male gender and Indian ethnicity were noted in our study. The
      diagnosis of CRP was often made clinically, and investigations were mainly
      ancillary. The treatment response was poor with antifungal agents but excellent
      with tetracyclines. The diagnostic criteria proposed by Davis et al. were found
      to be useful in our cohort of patients.

PMID- 25589051
TI  - Enhancing patient satisfaction in dermatology.
AB  - Patient satisfaction is an important component of dermatological care that
      reflects patients' perspectives on the care they receive. While physicians'
      expertise and judgment should always remain the foundation of providing
      appropriate and effective care, the patient experience can also be influenced by
      interpersonal relationships, expectations, and a sense of agency in the treatment
      patients receive. Dermatology providers can use practical techniques such as
      sitting rather than standing, reframing the concept of cure, and engaging
      patients in treatment decisions to improve the patient-provider experience and
      thereby optimize patient satisfaction. 

PMID- 25589052
TI  - Airborne hazards exposure and respiratory health of Iraq and Afghanistan
      veterans.
AB  - More than 2.6 million military personnel have been deployed to recent conflicts
      in Iraq and Afghanistan and were likely exposed to a variety of airborne hazards
      during deployment. Despite several epidemiologic reports of increased respiratory
      symptoms, whether or not these respiratory illnesses lead to reductions in lung
      function and/or specific pulmonary disease is unclear. We reviewed data published
      from 2001 to 2014 pertaining to respiratory health in military personnel deployed
      to Iraq and Afghanistan and found 19 unique studies. Study designs were primarily
      retrospective and observational in nature with patient symptom reporting and
      medical encounter data as primary outcome measures. Two case series reported on
      rare respiratory diseases, and one performed a standardized evaluation of new
      onset respiratory symptoms. Respiratory outcomes in relation to proximity to a
      specific air pollution source (i.e., smoke from burning trash and sulfur mine
      fire) were described in 2 separate studies. Only 2 longitudinal investigations
      were identified comparing pre- and postdeployment measurement of exercise
      capacity. In summary, published data based on case reports and retrospective
      cohort studies suggest a higher prevalence of respiratory symptoms and
      respiratory illness consistent with airway obstruction. However, the association
      between chronic lung disease and airborne hazards exposure requires further
      longitudinal research studies with objective pulmonary assessments. 

PMID- 25589053
TI  - Alcohol use and substance use disorders in Gulf War, Afghanistan, and Iraq War
      veterans compared with nondeployed military personnel.
AB  - Although recent veterans have been found to be at increased risk of psychiatric
      disorders, limited research has focused on alcohol or substance use disorders.
      This systematic review and meta-analysis examined whether alcohol or substance
      use disorders were more common in Gulf War, Afghanistan, and Iraq War veterans
      compared with military comparison groups nondeployed to the corresponding
      conflict, including never deployed personnel. Literature was searched (1990-2014)
      in multiple electronic databases. Studies were assessed for eligibility and
      quality, including risk of bias. Eighteen studies (1997-2014) met inclusion
      criteria. Pooled analysis based on a random-effects model yielded a summary odds
      ratio of 1.33 (95% confidence interval (CI): 1.22, 1.46) for alcohol (7 studies)
      and 2.13 (95% CI: 0.96, 4.72) for substance use (3 studies) disorders among Gulf
      War veterans, as well as 1.36 (95% CI: 1.11, 1.66) for alcohol (7 studies) and
      1.14 (95% CI: 1.04, 1.25) for substance use (4 studies) disorders among
      Iraq/Afghanistan veterans; meta-regressions found no statistically significant
      association between theater of war and alcohol use or substance use disorders.
      Our findings indicate that Gulf and Iraq/Afghanistan war veterans are at higher
      alcohol use disorder risk than nondeployed veterans, but further studies with
      increased power are needed to assess substance use disorder risk in Gulf War
      veteran populations. 

PMID- 25589054
TI  - Heart rate reduction and longevity in mice.
AB  - Heart rate correlates inversely with life span across all species, including
      humans. In patients with cardiovascular disease, higher heart rate is associated
      with increased mortality, and such patients benefit from pharmacological heart
      rate reduction. However, cause-and-effect relationships between heart rate and
      longevity, notably in healthy individuals, are not established. We therefore
      prospectively studied the effects of a life-long pharmacological heart rate
      reduction on longevity in mice. We hypothesized, that the total number of cardiac
      cycles is constant, and that a 15% heart rate reduction might translate into a
      15% increase in life span. C57BL6/J mice received either placebo or ivabradine at
      a dose of 50 mg/kg/day in drinking water from 12 weeks to death. Heart rate and
      body weight were monitored. Autopsy was performed on all non-autolytic cadavers,
      and parenchymal organs were evaluated macroscopically. Ivabradine reduced heart
      rate by 14% (median, interquartile range 12-15%) throughout life, and median life
      span was increased by 6.2% (p = 0.01). Body weight and macroscopic findings were
      not different between placebo and ivabradine. Life span was not increased to the
      same extent as heart rate was reduced, but nevertheless significantly prolonged
      by 6.2%.

PMID- 25589055
TI  - Reduction of no-reflow and reperfusion injury with the synthetic 17beta
      aminoestrogen compound Prolame is associated with PI3K/Akt/eNOS signaling
      cascade.
AB  - A high proportion of primary percutaneous coronary interventions performed in the
      setting of acute myocardial infarction, concur with inadequate myocardial
      perfusion at the microvascular level. This phenomenon, known as "no-reflow"
      contributes to reperfusion injury, poor prognosis and to unfavorable clinical
      outcome. In this study, we evaluated the hypothesis that the synthetic 17beta
      aminoestrogen Prolame, may confer cardioprotection and prevent against no-reflow.
      In an open-chest model of 30-min ischemia and 90-min reperfusion, male Wistar
      rats were randomly assigned to different groups: Control, Prolame, Prolame
      followed by the nitric oxide synthase inhibitor (L-NAME), and 17beta-estradiol.
      Areas of risk, infarct size and no-reflow were determined by planimetry with
      triphenyltetrazolium chloride and thioflavin-S stains. Structural damage of the
      vasculature was measured as capillary compression in clarified tissue after intra
      atrial injection of Microfil. Hemodynamic function was obtained at the end of
      stabilization, ischemia and reperfusion; nitric oxide (NO.) content was
      determined indirectly using the Griess reaction. Activation of the eNOS signaling
      cascade was determined by western blot. Prolame reduced the infarcted area,
      decreased the zones of no-reflow and capillary compression by activating the
      PI3K/Akt/eNOS signaling pathway in correlation with NO. increase. Prolame also
      activated endothelial cells augmenting NO. production, which was inhibited by
      ICI182780 (a selective estrogen receptor down-regulator), supporting the notion
      that the cardioprotective effect of Prolame involves the preservation of
      endothelium through the activation of estrogen receptor downstream signaling. Our
      results provide evidence that Prolame has potential therapeutic application in
      patients with AMI, as it prevents from both vascular and cardiac tissue damage. 

PMID- 25589056
TI  - An update on photodynamic therapies in the treatment of onychomycosis.
AB  - Onychomycosis is a common fungal infection of the nails that is increasing in
      prevalence in the old, diabetics and immunocompromised. Onychomycosis presents a
      therapeutic challenge that can lead to significant reductions in quality of life
      leading to both physical and psychological consequences. Current treatment
      modalities are difficult to implement due to the poor penetration of topical
      treatments to the nail bed, the slow growing nature of nails and the need for
      prolonged use of topical and/or oral medications. Standard of care medications
      have cure rates of 63-76% that leads to a high propensity of treatment failures
      and recurrences. Photodynamic therapy (PDT) offers an alternative treatment for
      onychomycosis. Methylene blue dye, methyl-aminolevulinate (MAL) and
      aminolevulinic acid (ALA) have been used as photosensitizers with approximately
      630 nm light. These modalities are combined with pre-treatment of urea and/or
      microabrasion for better penetration. PDT treatments are well tolerated with only
      mild transient pain, burning and erythema. In addition, significant cure rates
      for patients who have contraindications to oral medications or failed standard
      medications can be obtained. With further enhancements in photosensitizer
      permeability, decreased pre-treatment and photosensitizer incubation times, PDT
      can be a more efficient and cost-effective in office based treatment for
      onychomycosis. However, more large-scale randomized control clinical trials are
      needed to access the efficacy of PDT treatments. 

PMID- 25589057
TI  - Feasibility of establishing a biosafety level 3 tuberculosis culture laboratory
      of acceptable quality standards in a resource-limited setting: an experience from
      Uganda.
AB  - BACKGROUND: Despite the recent innovations in tuberculosis (TB) and multi-drug
      resistant TB (MDR-TB) diagnosis, culture remains vital for difficult-to-diagnose
      patients, baseline and end-point determination for novel vaccines and drug
      trials. Herein, we share our experience of establishing a BSL-3 culture facility
      in Uganda as well as 3-years performance indicators and post-TB vaccine trials
      (pioneer) and funding experience of sustaining such a facility. METHODS: Between
      September 2008 and April 2009, the laboratory was set-up with financial support
      from external partners. After an initial procedure validation phase in parallel
      with the National TB Reference Laboratory (NTRL) and legal approvals, the
      laboratory registered for external quality assessment (EQA) from the NTRL, WHO,
      National Health Laboratories Services (NHLS), and the College of American
      Pathologists (CAP). The laboratory also instituted a functional quality
      management system (QMS). Pioneer funding ended in 2012 and the laboratory
      remained in self-sustainability mode. RESULTS: The laboratory achieved
      internationally acceptable standards in both structural and biosafety
      requirements. Of the 14 patient samples analyzed in the procedural validation
      phase, agreement for all tests with NTRL was 90% (P <0.01). It started full
      operations in October 2009 performing smear microscopy, culture, identification,
      and drug susceptibility testing (DST). The annual culture workload was 7,636,
      10,242, and 2,712 inoculations for the years 2010, 2011, and 2012, respectively.
      Other performance indicators of TB culture laboratories were also monitored.
      Scores from EQA panels included smear microscopy >80% in all years from NTRL,
      CAP, and NHLS, and culture was 100% for CAP panels and above regional average
      scores for all years with NHLS. Quarterly DST scores from WHO-EQA ranged from 78%
      to 100% in 2010, 80% to 100% in 2011, and 90 to 100% in 2012. CONCLUSIONS: From
      our experience, it is feasible to set-up a BSL-3 TB culture laboratory with
      acceptable quality performance standards in resource-limited countries. With the
      demonstrated quality of work, the laboratory attracted more research groups and
      post-pioneer funding, which helped to ensure sustainability. The high skilled
      experts in this research laboratory also continue to provide an excellent
      resource for the needed national discussion of the laboratory and quality
      management systems.

PMID- 25589060
TI  - Abscisic acid and the key enzymes and genes in sucrose-to-starch conversion in
      rice spikelets in response to soil drying during grain filling.
AB  - MAIN CONCLUSION: Abscisic acid mediates the effect of post-anthesis soil drying
      on grain filling through regulating the activities of key enzymes and expressions
      of genes involved in sucrose-to-starch conversion in rice spikelets. This study
      investigated if abscisic acid (ABA) would mediate the effect of post-anthesis
      soil drying on grain filling through regulating the key enzymes in sucrose-to
      starch conversion in rice (Oryza sativa L.) spikelets. Two rice cultivars were
      field-grown. Three treatments, well-watered (WW), moderate soil drying (MD), and
      severe soil drying (SD), were imposed from 6 days after full heading until
      maturity. When compared with those under the WW, grain filling rate, grain
      weight, and sink activity, in terms of the activities and gene expression levels
      of sucrose synthase, ADP glucose pyrophosphorylase, starch synthase, and starch
      branching enzyme, in inferior spikelets were substantially increased under the
      MD, whereas they were markedly decreased in both superior and inferior spikelets
      under the SD. The two cultivars showed the same tendencies. Both MD and SD
      increased ABA content and expression levels of its biosynthesis genes in
      spikelets, with more increase under the SD than the MD. ABA content was
      significantly correlated with grain filling rate and sink activities under both
      WW and MD, while the correlations were not significant under the SD. Application
      of a low concentration ABA to WW plants imitated the results under the MD, and
      applying with a high concentration ABA showed the effect of the SD. The results
      suggest that ABA plays a vital role in grain filling through regulating sink
      activity and functions in a dose-dependent manner. An elevated ABA level under
      the MD enhances, whereas a too high level of ABA under the SD decreases, sink
      activity.

PMID- 25589061
TI  - Within-visit blood pressure variability is associated with prediabetes and
      diabetes.
AB  - We investigated the associations between within-visit blood pressure variability
      (BPV) and risk factors for cardiovascular disease (CVD). The study subjects
      included 17,795 people aged 40-74 years who underwent health check-ups in Aichi
      Prefecture, Japan, and completed two blood pressure measurements. Subjects were
      categorized into three groups according to the difference of systolic blood
      pressure (DeltaSBP), namely, low-BPV (<= 10 mmHg), moderate-BPV (11-20 mmHg), and
      high-BPV (> 20 mmHg). Subjects were also divided into three categories as those
      without prediabetes (glycosylated hemoglobin A1c [HbA1c] < 5.7%), prediabetes
      (HbA1c 5.7-6.4%) and diabetes (HbA1c >= 6.5% or under treatment for diabetes).
      The proportion of prediabetes and diabetes were significantly higher in subjects
      with high-BPV than in those with low-BPV after adjusting for age, sex, and mean
      SBP (odds ratio [95% confidence interval] was 1.16 [1.01-1.33] for prediabetes
      and 1.33 [1.06-1.66] for diabetes). Other CVD risk factors were not associated
      with high-BPV after the adjustment. In conclusion, increased within-visit BPV was
      significantly associated with the prevalence of prediabetes and diabetes,
      independent of mean SBP, in a large general population. Therefore, assessing BPV
      in a single visit may help to identify subjects at increased risk of impaired
      glycemic control.

PMID- 25589062
TI  - Influence of food condiments on the formation of carcinogenic heterocyclic amines
      in cooked chicken and determination by LC-MS/MS.
AB  - Heterocyclic amines (HCAs) are known to be suspected human carcinogens produced
      by high-temperature cooking of protein-rich foods such as meat and fish. In the
      present study, the influence of numerous food condiments on the formation of HCAs
      in cooked chicken was investigated. Chicken samples were subjected to pan-frying
      under controlled temperature. The levels of HCAs DMIP, MeIQx, 4,8-DiMeIQx, PhIP,
      harman and norharman were found to be between 0.93 and 27.52 ng g(-1), whereas
      IQ, MeIQ, AalphaC, MeAalphaC, Trp-P-1 and Trp-P-2 were found either below the
      limit of quantification or not detected in the control sample. Nevertheless, for
      samples cooked using food condiments, the amounts of HCAs (DMIP, MeIQx, 4,8
      DiMeIQx and PhIP) were between 0.14 and 19.57 ng g(-1); harman and norharman were
      detected at higher concentrations up to 17.77 ng g(-1) while IQ and MeIQ were at
      levels below the limit of quantification; and AalphaC, MeAalphaC, Trp-P-1 and Trp
      P-2 were not detected in any of the samples. The outcomes revealed that the
      formation of HCAs (except harman and norharman) diminished after the addition of
      food condiments. Edible oil contributed to the highest levels of HCA formation,
      followed by garlic, paprika, pepper and tomato.

PMID- 25589063
TI  - Personalized- and one- medicine: bioinformatics foundation in health and its
      economic feasibility.
AB  - Personalized medicine's foundation rests on the use of molecular technologies,
      which are being used to identify genetic mutations, polymorphisms, and variants
      that can be associated with an individual's genetic make up, revealing risk
      factors and predictive data. Needless to say this same analysis can be performed
      on various types of cancers, including samples stored for many years under the
      right conditions. For the most part, these technologies employ microarray and RNA
      Seq methodologies, which examine large numbers of gene expressions at a time,
      providing clustering and patterns of this expression. The methodologies and their
      evaluative outcomes further demonstrate that more than a single gene is involved
      with various phenomena. However, given the mass of data emerging from this
      analysis, and commonalities they reveal between various phenomena/disorders,
      achieving 100% certainty may not be that easy. Another outcome from this massive
      store of molecular data is the concept of one medicine. This field has been
      developed by researchers in a variety of disciplines (e.g., medical and
      veterinary science) that advocate for greater integration of animal and human
      health. One medicine takes advantage of the fact that molecular commonalities in
      major biochemical pathways occur because of evolutionary conservation, which is
      dependent on stereospecificity. In this regard, the foci of personalized medicine
      and one medicine are quite broad and require trained professionals, as well as a
      lowering of cost in order to be better integrated into mainstream medical
      practice.

PMID- 25589065
TI  - Sharing clinical trial data should become the "expected norm," US panel says.

PMID- 25589064
TI  - Tick-borne haemoparasites in African buffalo (Syncerus caffer) from two wildlife
      areas in Northern Botswana.
AB  - BACKGROUND: The African buffalo (Syncerus caffer) is a host for many pathogens
      known to cause economically important diseases and is often considered an
      important reservoir for livestock diseases. Theileriosis, heartwater, babesiosis
      and anaplasmosis are considered the most important tick-borne diseases of
      livestock in sub-Saharan Africa, resulting in extensive economic losses to
      livestock farmers in endemic areas. Information on the distribution of tick-borne
      diseases and ticks is scarce in Northern Botswana. Nevertheless, this data is
      necessary for targeting surveillance and control measures in livestock production
      at national level. METHODS: In order to address this gap, we analyzed 120 blood
      samples from buffalo herds for the presence of common tick-borne haemoparasites
      causing disease in livestock, collected in two of the main wildlife areas of
      Northern Botswana: the Chobe National Park (CNP, n=64) and the Okavango Delta
      (OD, n=56). RESULTS: Analysis of the reverse line blot (RLB) hybridization assay
      results revealed the presence of Theileria, Babesia, Anaplasma and Ehrlichia
      species, either as single or mixed infections. Among the Theileria spp. present,
      T. parva (60%) and T. mutans (37%) were the most prevalent. Other species of
      interest were Anaplasma marginale subsp. centrale (30%), A. marginale (20%),
      Babesia occultans (23%) and Ehrlichia ruminantium (6%). The indirect fluorescent
      antibody test (IFAT) indicated 74% of samples to be positive for the presence of
      T. parva antibodies. Quantitative real-time PCR (qPCR) detected the highest level
      of animals infected with T. parva (81% of the samples). The level of agreement
      between the tests for detection of T. parva positive animals was higher between
      qPCR and IFAT (kappa=0.56), than between qPCR and RLB (kappa=0.26) or the latter
      and IFAT (kappa=0.15). CONCLUSIONS: This is the first report of tick-borne
      haemoparasites in African buffalo from northern Botswana, where animals from the
      CNP showed higher levels of infection than those from OD. Considering the absence
      of fences separating wildlife and livestock in the CNP and the higher levels of
      some parasite species in buffalo from that area, surveillance of tick-borne
      diseases in livestock at the interface in the CNP should be prioritized.

PMID- 25589066
TI  - High-mobility group box 1: a novel target for treatment of Pseudomonas aeruginosa
      keratitis.
AB  - High-mobility group box 1 (HMGB1), a prototypic alarmin, mediates the systemic
      inflammatory response syndrome. Treatment with vasoactive intestinal peptide, an
      anti-inflammatory neuropeptide, downregulates proinflammatory cytokines and
      promotes healing in a susceptible (cornea perforates) model of Pseudomonas
      aeruginosa keratitis, and also significantly downregulates HMGB1 expression.
      Therefore, we examined targeting HMGB1 for the treatment of P. aeruginosa
      keratitis to avoid delivery and other issues associated with vasoactive
      intestinal peptide. For this, HMGB1 was silenced using small interfering RNA,
      whereas controls were treated with a nonspecific scrambled sequence small
      interfering RNA. Less disease was seen postinfection in siHMGB1 compared with
      control mice and was documented by clinical score and photographs with a slit
      lamp. Real-time RT-PCR and ELISA confirmed HMGB1 knockdown. RT-PCR analysis also
      revealed reduced mRNA levels of IL-1beta, MIP-2, TNF-alpha, TLR4, and receptor
      for advanced glycation end products, whereas mRNA levels of anti-inflammatory
      TLRs single Ig IL-1-related receptor and ST2 were increased significantly. HMGB1
      knockdown also decreased IL-1beta and MIP-2 proteins, reducing polymorphonuclear
      cell number in the infected cornea. mRNA and protein levels of CXCL12 and CXCR4,
      as well as mononuclear cells, were reduced significantly after HMGB1 knockdown.
      Ab neutralization of HMGB1, infection with a clinical isolate, and recombinant
      HMGB1 treatment of resistant mice supported the silencing studies. These data
      provide evidence that silencing HMGB1 promotes better resolution of P. aeruginosa
      keratitis by decreasing levels of proinflammatory mediators (decreasing
      polymorphonuclear cell infiltration), increasing anti-inflammatory TLRs, reducing
      CXCL12 (preventing HMGB1/CXCL12 heterodimer formation), and signaling through
      CXCR4, reducing monocyte/macrophage infiltration. 

PMID- 25589067
TI  - A novel regulatory macrophage induced by a helminth molecule instructs IL-10 in
      CD4+ T cells and protects against mucosal inflammation.
AB  - Immunomodulation is a common feature of chronic helminth infections and mainly
      attributed to the secretion of bioactive molecules, which target and modify host
      immune cells. In this study, we show that the helminth immunomodulator
      AvCystatin, a cysteine protease inhibitor, induces a novel regulatory macrophage
      (Mreg; AvCystatin-Mreg), which is sufficient to mitigate major parameters of
      allergic airway inflammation and colitis in mice. A single adoptive transfer of
      AvCystatin-Mreg before allergen challenge suppressed allergen-specific IgE
      levels, the influx of eosinophils into the airways, local and systemic Th2
      cytokine levels, and mucus production in lung bronchioles of mice, whereas
      increasing local and systemic IL-10 production by CD4(+) T cells. Moreover, a
      single administration of AvCystatin-Mreg during experimentally induced colitis
      strikingly reduced intestinal pathology. Phenotyping of AvCystatin-Mreg revealed
      increased expression of a distinct group of genes including LIGHT, sphingosine
      kinase 1, CCL1, arginase-1, and costimulatory molecules, CD16/32, ICAM-1, as well
      as PD-L1 and PD-L2. In cocultures with dendritic cells and CD4(+) T cells,
      AvCystatin-Mreg strongly induced the production of IL-10 in a cell-contact
      independent manner. Collectively, our data identify a specific suppressive
      macrophage population induced by a single parasite immunomodulator, which
      protects against mucosal inflammation. 

PMID- 25589069
TI  - Vaccine adjuvant MF59 promotes retention of unprocessed antigen in lymph node
      macrophage compartments and follicular dendritic cells.
AB  - Ag retention within lymph nodes (LNs) upon vaccination is critical for the
      development of adaptive immune responses, because it facilitates the encounter of
      the Ag with cognate lymphocytes. During a secondary exposure of the immune system
      to an Ag, immune complexes (ICs) that contain the unprocessed Ag are captured by
      subcapsular sinus macrophages and are transferred onto follicular dendritic
      cells, where they persist for weeks, facilitating Ag presentation to cognate
      memory B cells. The impact of adjuvants on Ag retention within the draining LNs
      is unknown. In this article, we provide the first evidence, to our knowledge,
      that the oil-in-water emulsion adjuvant MF59 localizes in subcapsular sinus and
      medullary macrophage compartments of mouse draining LNs, where it persists for at
      least 2 wk. In addition, we demonstrate that MF59 promotes accumulation of the
      unprocessed Ag within these LN compartments and facilitates the consequent
      deposition of the IC-trapped Ag onto activated follicular dendritic cells. These
      findings correlate with the ability of MF59 to boost germinal center generation
      and Ag-specific Ab titers. Our data suggest that the adjuvant effect of MF59 is,
      at least in part, due to an enhancement of IC-bound Ag retention within the LN
      and offer insights to improve the efficacy of new vaccine adjuvants. 

PMID- 25589070
TI  - 5-lipoxygenase is a direct target of miR-19a-3p and miR-125b-5p.
AB  - 5-Lipoxygenase (5-LO) is the key enzyme in leukotriene biosynthesis. Leukotrienes
      are mediators of the innate immune system and inflammatory processes, and they
      might also be involved in cancer development. MicroRNAs (miRNAs) are important
      translational regulators and have been shown to be involved in development,
      differentiation, and cancer. Unraveling the miRNA network is important for
      understanding the cellular regulation processes. We identified two new miRNAs,
      miR-19a-3p and miR-125b-5p, regulating 5-LO and confirmed direct interaction by
      reporter gene assays. Furthermore, we investigated the regulation of 5-LO by
      these two miRNAs in several cell types. Inhibition of both miRNAs by antagomirs
      during differentiation of the myeloid cell line Mono Mac 6 led to a significant
      increase in 5-LO protein expression. Stimulation of human T lymphocytes with PHA
      resulted in a strong downregulation of 5-LO mRNA expression and in the induction
      of miR-19a-3p. The inhibition of miR-19a-3p with an antagomir led to a
      significant increase in 5-LO mRNA expression in T lymphocytes. Taken together,
      our data reveal that miR-19a-3p and miR-125b-5p target 5-LO in a cell type- and
      stimulus-specific manner. 

PMID- 25589068
TI  - Cytotoxic mediators in paradoxical HIV-tuberculosis immune reconstitution
      inflammatory syndrome.
AB  - Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS)
      frequently complicates combined antiretroviral therapy and antituberculosis
      therapy in HIV-1-coinfected tuberculosis patients. The immunopathological
      mechanisms underlying TB-IRIS are incompletely defined, and improved
      understanding is required to derive new treatments and to reduce associated
      morbidity and mortality. We performed longitudinal and cross-sectional analyses
      of human PBMCs from paradoxical TB-IRIS patients and non-IRIS controls (HIV-TB
      coinfected patients commencing antiretroviral therapy who did not develop TB
      IRIS). Freshly isolated PBMC stimulated with heat-killed Mycobacterium
      tuberculosis H37Rv (hkH37Rv) were used for IFN-gamma ELISPOT and RNA extraction.
      Stored RNA was used for microarray and RT-PCR, whereas corresponding stored
      culture supernatants were used for ELISA. Stored PBMC were used for perforin and
      granzyme B ELISPOT and flow cytometry. There were significantly increased IFN
      gamma responses to hkH37Rv in TB-IRIS, compared with non-IRIS PBMC (p = 0.035).
      Microarray analysis of hkH37Rv-stimulated PBMC indicated that perforin 1 was the
      most significantly upregulated gene, with granzyme B among the top five (log2
      fold difference 3.587 and 2.828, respectively), in TB-IRIS. Downstream
      experiments using RT-PCR, ELISA, and ELISPOT confirmed the increased expression
      and secretion of perforin and granzyme B. Moreover, granzyme B secretion reduced
      in PBMC from TB-IRIS patients during corticosteroid treatment. Invariant NKT cell
      (CD3(+)Valpha24(+)) proportions were higher in TB-IRIS patients (p = 0.004) and
      were a source of perforin. Our data implicate the granule exocytosis pathway in
      TB-IRIS pathophysiology. Further understanding of the immunopathogenesis of this
      condition will facilitate development of specific diagnostic and improved
      therapeutic options. 

PMID- 25589071
TI  - The unappreciated intracellular lifestyle of Blastomyces dermatitidis.
AB  - Blastomyces dermatitidis, a dimorphic fungus and the causative agent of
      blastomycosis, is widely considered an extracellular pathogen, with little
      evidence for a facultative intracellular lifestyle. We infected mice with spores,
      that is, the infectious particle, via the pulmonary route and studied
      intracellular residence, transition to pathogenic yeast, and replication inside
      lung cells. Nearly 80% of spores were inside cells at 24 h postinfection with
      10(4) spores. Most spores were located inside of alveolar macrophages, with
      smaller numbers in neutrophils and dendritic cells. Real-time imaging showed
      rapid uptake of spores into alveolar macrophages, conversion to yeast, and
      intracellular multiplication during in vitro coculture. The finding of multiple
      yeast in a macrophage was chiefly due to intracellular replication rather than
      multiple phagocytic events or fusion of macrophages. Depletion of alveolar
      macrophages curtailed infection in mice infected with spores and led to a 26-fold
      reduction in lung CFU by 6 d postinfection versus nondepleted mice. Phase
      transition of the spores to yeast was delayed in these depleted mice over a time
      frame that correlated with reduced lung CFU. Spores cultured in vitro converted
      to yeast faster in the presence of macrophages than in medium alone. Thus,
      although advanced B. dermatitidis infection may exhibit extracellular residence
      in tissue, early lung infection with infectious spores reveals its unappreciated
      facultative intracellular lifestyle. 

PMID- 25589073
TI  - Selective blockade of CD28-mediated T cell costimulation protects rhesus monkeys
      against acute fatal experimental autoimmune encephalomyelitis.
AB  - Costimulatory and coinhibitory receptor-ligand pairs on T cells and APC control
      the immune response. We have investigated whether selective blockade of CD28
      CD80/86 costimulatory interactions, which preserves the coinhibitory CTLA4
      CD80/86 interactions and the function of regulatory T (Treg) cells, abrogates the
      induction of experimental autoimmune encephalomyelitis (EAE) in rhesus monkeys.
      EAE was induced by intracutaneous immunization with recombinant human myelin
      oligodendrocyte glycoprotein (rhMOG) in CFA on day 0. FR104 is a monovalent,
      PEGylated-humanized Fab' Ab fragment against human CD28, cross-reactive with
      rhesus monkey CD28. FR104 or placebo was administered on days 0, 7, 14, and 21.
      FR104 levels remained high until the end of the study (day 42). Placebo-treated
      animals all developed clinical EAE between days 12 and 27. FR104-treated animals
      did not develop clinical EAE and were sacrificed at the end of the study
      resulting in a significantly prolonged survival. FR104 treatment diminished T and
      B cell responses against rhMOG, significantly reduced CNS inflammation and
      prevented demyelination. The inflammatory profile in the cerebrospinal fluid and
      brain material was also strongly reduced. Recrudescence of latent virus was
      investigated in blood, spleen, and brain. No differences between groups were
      observed for the beta-herpesvirus CMV and the polyomaviruses SV40 and SA12. Cross
      sectional measurement of lymphocryptovirus, the rhesus monkey EBV, demonstrated
      elevated levels in the blood of FR104-treated animals. Blocking rhesus monkey
      CD28 with FR104 mitigated autoreactive T and B cell activation and prevented CNS
      pathology in the rhMOG/CFA EAE model in rhesus monkeys. 

PMID- 25589074
TI  - Monitoring and cell-specific deletion of C5aR1 using a novel floxed GFP-C5aR1
      reporter knock-in mouse.
AB  - Many of the biological properties of C5a are mediated through activation of its
      receptor (C5aR1), the expression of which has been demonstrated convincingly on
      myeloid cells, such as neutrophils, monocytes, and macrophages. In contrast,
      conflicting results exist regarding C5aR1 expression in dendritic cells (DCs) and
      lymphoid lineage cells. In this article, we report the generation of a floxed GFP
      C5aR1 reporter knock-in mouse. Using this mouse strain, we confirmed strong C5aR1
      expression in neutrophils from bone marrow, blood, lung, and spleen, as well as
      in peritoneal macrophages. Further, we show C5aR1 expression in lung eosinophils,
      lung- and lamina propria-resident and alveolar macrophages, bone marrow-derived
      DCs, and lung-resident CD11b(+) and monocyte-derived DCs, whereas intestinal and
      pulmonary CD103(+) DCs stained negative. Also, some splenic NKT cells expressed
      GFP, whereas naive NK cells and B2 cells lacked GFP expression. Finally, we did
      not observe any C5aR1 expression in naive or activated CD4(+) Th cells in vitro
      or in vivo. Mating the floxed GFP-C5aR1 mouse strain with LysMCre mice, we were
      able to specifically delete C5aR1 in neutrophils and macrophages, whereas C5aR1
      expression was retained in DCs. In summary, our findings suggest that C5aR1
      expression in mice is largely restricted to cells of the myeloid lineage. The
      novel floxed C5aR1 reporter knock-in mouse will prove useful to track C5aR1
      expression in experimental models of acute and chronic inflammation and to
      conditionally delete C5aR1 in immune cells. 

PMID- 25589072
TI  - TLR signaling modulates side effects of anticancer therapy in the small
      intestine.
AB  - Intestinal mucositis represents the most common complication of intensive
      chemotherapy, which has a severe adverse impact on quality of life of cancer
      patients. However, the precise pathophysiology remains to be clarified, and there
      is so far no successful therapeutic intervention. In this study, we investigated
      the role of innate immunity through TLR signaling in modulating genotoxic
      chemotherapy-induced small intestinal injury in vitro and in vivo. Genetic
      deletion of TLR2, but not MD-2, in mice resulted in severe chemotherapy-induced
      intestinal mucositis in the proximal jejunum with villous atrophy, accumulation
      of damaged DNA, CD11b(+)-myeloid cell infiltration, and significant gene
      alterations in xenobiotic metabolism, including a decrease in ABCB1/multidrug
      resistance (MDR)1 p-glycoprotein (p-gp) expression. Functionally, stimulation of
      TLR2 induced synthesis and drug efflux activity of ABCB1/MDR1 p-gp in murine and
      human CD11b(+)-myeloid cells, thus inhibiting chemotherapy-mediated cytotoxicity.
      Conversely, TLR2 activation failed to protect small intestinal tissues
      genetically deficient in MDR1A against DNA-damaging drug-induced apoptosis. Gut
      microbiota depletion by antibiotics led to increased susceptibility to
      chemotherapy-induced mucosal injury in wild-type mice, which was suppressed by
      administration of a TLR2 ligand, preserving ABCB1/MDR1 p-gp expression. Findings
      were confirmed in a preclinical model of human chemotherapy-induced intestinal
      mucositis using duodenal biopsies by demonstrating that TLR2 activation limited
      the toxic-inflammatory reaction and maintained assembly of the drug transporter p
      gp. In conclusion, this study identifies a novel molecular link between innate
      immunity and xenobiotic metabolism. TLR2 acts as a central regulator of
      xenobiotic defense via the multidrug transporter ABCB1/MDR1 p-gp. Targeting TLR2
      may represent a novel therapeutic approach in chemotherapy-induced intestinal
      mucositis. 

PMID- 25589075
TI  - Cutting edge: stage-specific requirement of IL-18 for antiviral NK cell
      expansion.
AB  - Although NK cells are considered part of the innate immune system, recent studies
      have demonstrated the ability of Ag-experienced NK cells to become long-lived and
      contribute to potent recall responses similar to T and B cells. The precise
      signals that promote the generation of a long-lived NK cell response are largely
      undefined. In this article, we demonstrate that NK cells require IL-18 signaling
      to generate a robust primary response during mouse CMV (MCMV) infection but do
      not require this signal for memory cell maintenance or recall responses. IL-12
      signaling and STAT4 in activated NK cells increased the expression of the adaptor
      protein MyD88, which mediates signaling downstream of the IL-18 and IL-1
      receptors. During MCMV infection, NK cells required MyD88, but not IL-1R, for
      optimal expansion. Thus, an IL-18-MyD88 signaling axis facilitates the prolific
      expansion of NK cells in response to primary viral infection, but not recall
      responses. 

PMID- 25589077
TI  - Zoonotic bacterial pathogens and mixed crop-livestock farming.
AB  - Use of mixed crop-livestock farms (MCLFs) is one of the oldest and most
      traditional farming methods practiced all over the world, and MCLFs are still one
      of the major systems of food production, particularly for organic foods. On these
      typically small farms, livestock are reared primarily on grass and naturally
      grown crops, while composted animal wastes are used to fertilize the soil for
      growing crops. Specific to organic MCLFs, biosecurity challenges arise from the
      fact that animals are reared outdoors, which increases potential for contact with
      disease vectors including wild birds, rodents, and insects. Organic regulations
      do not allow the use of chemicals and antibiotics; therefore, alternative methods
      for control of disease and zoonotic pathogens must be used. Due to the
      biosecurity challenges and the complexity of the MCLF environment, methods for
      control of zoonotic pathogens need to be carefully considered in order to be
      effective and to abide by organic regulations if required. The objectives of this
      study are to define the complex routes of transmission, as well as the prevalence
      of potential zoonotic and possible interruption strategies of these pathogens
      among the food animals and crops produced on MCLFs.

PMID- 25589078
TI  - Functional properties of bicarbonates and lactic acid on chicken breast retail
      display properties and cooked meat quality.
AB  - Whole chicken breast was injected with potassium bicarbonate (PB), sodium
      bicarbonate (SB), and potassium lactate (K-lactate) and salt, alone or in
      combination at different concentration levels. The objectives were to 1)
      investigate the effects of different concentration of PB, SB, and PL on
      instrumental color, water-holding capacity (WHC), objective tenderness,
      expressible moisture, and moisture content and 2) evaluate whether sodium
      containing ingredients can be replaced with potassium as a potential strategy to
      reduce total sodium content in the finished product. Results showed that chicken
      breast tissue marinated with SB and PB had greater moisture retention, display
      characteristics, and cooked product qualities than chicken breast tissue injected
      with water and the nonmarinated control. The L* values (lightness) did not change
      over the period of retail display and were not different compared to the control
      (P>0.05). The chicken breast enhanced with SB, PB, and K-lactate retained better
      retail display color than the controls (marinated with water and nonmarinated).
      Increasing the potassium bicarbonate concentration from 0.5 to 1.5% significantly
      improved the water-holding capacity (82.17 to 92.61%; P<0.05) and led to better
      cook yield (83.84 to 91.96%). Shear force values were lower at the 0.5% level for
      both SB and PB compared to the control. PB performed better on retail display and
      cooked meat quality than SB. This study suggests that chicken breast tissue can
      be marinated with KB as a healthier alternative to phosphate or SB.

PMID- 25589079
TI  - Genetic analysis of leg problems and growth in a random mating broiler
      population.
AB  - Improvement in growth has been widely reported as the cause of increased
      incidence of leg problems in broiler chickens. We report herein the genetic
      relationship between growth and leg problems in a random mating broiler control
      population. The traits studied were valgus (VL), varus (VR), and tibial
      dyschondroplasia (TD), which were expressed on a binary scale of 0 (normal) and 1
      (abnormal); growth rates from 0 to 4 wk (BWG 0-4) and from 0 to 6 wk of age (BWG
      0-6); and residual feed intake from 5 to 6 wk of age (RFI 5-6). A threshold
      linear mixed model was employed for the joint analysis of the categorical and
      linear traits. Incidences of VL, VR, and TD were 26, 4, and 2%, respectively.
      Heritability of leg problems ranged from 0.11 to 0.13. Phenotypic correlations
      alluded to an unfavorable relationship between growth and leg problems; however,
      the genetic relationship between growth and leg problems was extremely weak,
      ranging from 0.01 to 0.08. There is, therefore, a basis for genetic improvement
      in leg problems. However, improved management practices would also be important
      to reduce incidence of leg problems in broiler chickens. 

PMID- 25589076
TI  - Macronutrient deprivation modulates antigen trafficking and immune recognition
      through HSC70 accessibility.
AB  - B lymphocytes exploit macroautophagy to capture cytoplasmic and nuclear proteins
      within autophagosomes. Fusion of autophagosomes with lysosomes and endosomes
      facilitates content proteolysis, with the resulting peptides selectively binding
      MHC class II (MHC II) molecules, which are displayed for recognition by T
      lymphocytes. Nutrient deprivation or stress amplified this pathway, favoring
      increased MHC II presentation of cytoplasmic Ags targeted to autophagosomes. By
      contrast, this stress diminished MHC II presentation of membrane Ags including
      the BCR and cytoplasmic proteins that use the chaperone-mediated autophagy
      pathway. Whereas intracellular protease activity increased with nutrient stress,
      endocytic trafficking and proteolytic turnover of the BCR was impaired. Addition
      of macronutrients such as high molecular mass proteins restored endocytosis and
      Ag presentation, evidence of tightly regulated membrane trafficking dependent on
      macronutrient status. Altering cellular levels of the cytosolic chaperone HSC70
      was sufficient to overcome the inhibitory effects of nutritional stress on BCR
      trafficking and Ag presentation. Together, these results reveal a key role for
      macronutrient sensing in regulating immune recognition and the importance of
      HSC70 in modulating membrane trafficking pathways during cellular stress. 

PMID- 25589080
TI  - Photostimulation of Japanese quail.
AB  - To adapt commercial poultry production to a new scenario of energy savings and to
      develop specific practices for quail production aimed at reducing costs while
      maintaining or improving productivity, four experiments were conducted. In the
      first experiment, birds were allocated to four treatments (photoperiod duration):
      T1: 14 L:10 D; T2: 15 L:9 D; T3: 16 L:8 D; and T4: 17 L:7 D. In the second
      experiment, birds were subjected to four levels of brightness: T1: 5 lux; T2: 10
      lux; T3:15 lux; and T4: 22 lux (control). In the third experiment, four types of
      lamps were evaluated: T1: compact fluorescent lamp (color temperature: 6,500 K);
      T2: compact fluorescent lamp (color temperature: 2,700 K); T3: incandescent lamp;
      and T4: yellow LED. In the last experiment, four lighting programs were compared:
      T1: continuous program (control), in which there was a single photoperiod of 15
      h; the other treatments consisted of intermittent lighting programs, as follows:
      T2: 1 h of light provided 1 h after dusk; T3: 1 h of light provided 2 h before
      dawn; T4: half an hour of light provided 1 h after dusk and half an hour of light
      provided 1.5 h before dawn. In each experiment, 1,296 Japanese quail were
      evaluated for four 28-d cycles, totaling 112 experimental days. A completely
      randomized experimental design of 4 treatments with 12 replicates of 27 birds
      each was applied in all trials. Performance and egg quality were evaluated in
      each experiment. Higher egg production and adequate egg quality, as well as
      energy savings, can be obtained with Japanese quail using compact fluorescent
      lamps or LEDs and a photoperiod of 15 h/d supplied using an intermittent lighting
      program, with 1 h of artificial light 2 h before dawn at a brightness of 5 lux.

PMID- 25589081
TI  - Development of intestinal mucin 2, IgA, and polymeric Ig receptor expressions in
      broiler chickens and Pekin ducks.
AB  - Intestinal mucin 2 (MUC2), a major gel-forming mucin, represents a primary
      barrier component of mucus layers and a target site for secretory IgA. Polymeric
      Ig receptor (pIgR) expressed on the basolateral surface of epithelium is used to
      transport polymeric IgA from the lamina propria into luminal mucins to establish
      the first lines of intestinal defense. To determine the spatio-temporal
      expression of MUC2, IgA, and pIgR in broiler chickens and Pekin ducks, intestinal
      tissues (n=6/age) were dissected from late embryonic days up to 21 d posthatch.
      In the intestinal tissues, MUC2 was expressed with a rapid increase at hatching,
      followed by steady expression through 21 d posthatch both in chickens and ducks.
      IgA expression was low during the first week following hatching for both species.
      From the second week posthatch, IgA was rapidly expressed in the chickens,
      arriving at steady expression in the third week after hatching. However, in
      ducks, IgA expression during the 2 to 3 wk posthatch period was relatively slow.
      The expression of pIgR was greatly increased after hatching for both species, but
      its expression in ducks was relatively delayed. In addition, intestinal pIgR
      expression was highly correlated with MUC2 and IgA expressions in chickens but
      just moderately correlated in ducks. The relatively slow and late expression of
      IgA and pIgR as well as their moderate correlation may or may not account for the
      susceptibility of ducklings to mucosal pathogens at a young age.

PMID- 25589082
TI  - Genetic parameters for body weight in meat quail.
AB  - The aim of this study was to estimate genetic parameters for BW in meat quail at
      different ages. A total of 24,382 weight records from 3,652 quail, born between
      2009 and 2011, were evaluated. Weekly BW was measured from hatch until 42 d of
      age. The genetic parameters were estimated by the restricted maximum likelihood
      method using a multivariate animal model. Heritability of BW ranged from 0.03 to
      0.23. Genetic correlations were mainly high and positive. Selection for BW at 28
      d of age yielded good indirect genetic progress in BW at 42 d of age. 

PMID- 25589083
TI  - Cloacal and surface temperatures of tom turkeys exposed to different rearing
      temperature regimes during the first 12 weeks of growth.
AB  - Years of genetic selection have caused an increase in growth rate and market body
      mass in agricultural poultry species compared to earlier genetic strains,
      potentially altering their physiological requirements. The objective of this
      study was to expose Hybrid Converter tom turkeys on a weekly basis to the
      recommended rearing temperature regime (TCON: control) or 4 degrees C below the
      recommended standard (TTRT: treatment) to determine their thermal responses. Once
      per week for 12 weeks, 12 turkeys were individually exposed to either TCON or
      TTRT for a 2-h period. Surface temperatures of the breast (TBREAST), wing
      (TWING), drumstick (TDRUM), head (THEAD), and shank (TSHANK) were measured at 20
      min intervals using an infrared camera, while a thermal data logger measured the
      skin surface temperature under the wing (TLOGGER) at 30-s intervals. The cloacal
      temperature (TCORE) was measured using a medical thermometer at the start and end
      of the exposure period. Regardless of exposure temperature, the TBREAST (TCON:
      P<0.001 and TTRT: P<0.001), TWING (TCON: P<0.001 and TTRT: P<0.001), and TDRUM
      (TCON: P<0.001 and TTRT: P<0.001) decreased from weeks 4 to 6 and remained
      constant from weeks 1 to 3 and 8 to 12. THEAD was elevated in week 2 (TCON:
      P<0.001) or week 3 (TTRT: P<0.001), TSHANK increased slightly during week 3 for
      both TCON (P<0.001) and TTRT (P<0.001), and TLOGGER (TCON: P<0.001 and TTRT:
      P=0.001) and TCORE (TCON: P<0.001 and TTRT: P<0.001) were lower during the first
      week. Thereafter, THEAD, TSHANK, TLOGGER, and TCORE remained constant. Exposure
      to TTRT resulted in lower TBREAST, TWING, and TDRUM compared to TCON. Generally,
      THEAD, TSHANK, TLOGGER, and TCORE were not affected by the different exposure
      temperatures. The data demonstrated that the degree of thermal response expressed
      is dependent on the location of measurement, age, and exposure temperature.

PMID- 25589084
TI  - Four Measures of Change in Physiologic State During the Feeding Period of Very
      Premature Infants.
AB  - Precise assessment of infants' ability to regulate feeding challenges requires
      modeling of physiologic values across intervals of the feeding period without
      smoothing too much of the data stream. Using a subset of data from a study of
      physiologic stability and feeding performance in very preterm (<=30 weeks'
      gestational age) infants fed in two different feeding positions, this exploratory
      study compared mean heart rate (HR) and its coefficient of variation sampled
      during the feeding period using four methods: (1) dividing the feeding period
      into three equal intervals; (2) extracting 2-min intervals from the initial,
      middle, and final third of the feeding period; (3) using successive 2-min
      intervals during the first 6 min of feeding; and (4) using successive 2-min
      intervals during the entire feeding period. Power analysis simulation was
      conducted with varying numbers of subjects to determine the method that requires
      the least number of subjects to detect a position effect for change in HR across
      time with 80% power. Different patterns of HR change across the feeding period
      were observed across the methods, which suggest potential advantages and
      disadvantages of each method. Among the four methods, using the first 6 min of
      the feeding period required the fewest subjects to detect significant differences
      in changes in HR across time between the feeding positions. 

PMID- 25589085
TI  - The Efficacy of a Family-Based Intervention Program on Childhood Obesity: A Quasi
      Experimental Design.
AB  - The purpose of this quasi-experimental study was to assess the efficacy of a
      family-based (FB) weight-loss and behavior-modification intervention among
      overweight/obese children (age 9-11 years) and their parents in Taiwan. The
      intervention group (52 child-parent dyads) participated in an FB program for 7
      weeks. The control group (55 child-parent dyads) received an educational pamphlet
      about obesity prevention. The children's body mass index (BMI) z-scores were the
      primary outcome variable. The parents' BMI, high-calorie (HC) food-intake
      behaviors, screen-related behaviors, and restrictions on children's consumption
      of HC foods and screen-related behaviors and the availability of HC foods at home
      were the secondary outcome variables. Outcome variables were measured at baseline
      (T0), at the end of the intervention (T1), and 4 weeks after the end of the
      intervention (T2). A linear mixed model was used to assess the efficacy of the FB
      program. Results indicated that the children's BMI z-scores decreased
      significantly more from T0 to T2 in the experimental group than in the control
      group. The decreases in parents' HC food-intake behaviors and availability of HC
      foods at home and the increase in parental restrictions on children's consumption
      of HC foods were significantly greater in the experimental than in the control
      group from T0 to T1 and T0 to T2. The FB program was effective in modifying
      parental behaviors and the weight of overweight/obese children in a Taiwanese
      population. 

PMID- 25589087
TI  - Tackling fears about exercise is important for ME treatment, analysis indicates.

PMID- 25589086
TI  - Illness perception in Polish patients with chronic diseases: Psychometric
      properties of the Brief Illness Perception Questionnaire.
AB  - The study evaluates the psychometric properties of a Polish translation of the
      Brief Illness Perception Questionnaire. A total of 276 patients with chronic
      conditions (58.7% women) completed the Brief Illness Perception Questionnaire and
      the Hospital Anxiety and Depression Scale. The internal consistency of the Polish
      Brief Illness Perception Questionnaire measured with Cronbach's alpha was
      satisfactory (alpha = 0.74). Structural validity was demonstrated by significant
      inter-correlations between the Brief Illness Perception Questionnaire components.
      Discriminant validity was supported by the fact that the Brief Illness Perception
      Questionnaire enables patients with various conditions to be differentiated.
      Significant correlations were found between Brief Illness Perception
      Questionnaire and depression and anxiety levels. The Polish Brief Illness
      Perception Questionnaire thus evaluated is a reliable and valid tool.

PMID- 25589088
TI  - Under-representation of women on governing bodies: women general practitioners on
      Clinical Commissioning Groups in England.
AB  - Recently formed Clinical Commissioning Groups in the English National Health
      Service have important responsibility for commissioning local health and care
      services. Women are under-represented on the governing bodies of these
      significant primary care based organizations despite the fact that they
      constitute almost half of the general practitioner workforce in England. This
      essay examines some of the reasons for this under-representation including the
      predominance of women in the salaried and part-time sector of general practice
      and gendered management styles within the National Health Service. It is argued
      that the under-representation of women on Clinical Commissioning Group governing
      bodies matters in terms of social justice, representation of the broader
      community and role models. 

PMID- 25589090
TI  - Dermatology has been decimated by political meddling.

PMID- 25589089
TI  - Prevalence of major depressive disorder among spouses of men who use alcohol in a
      rural community in Central Sri Lanka.
AB  - AIMS: To estimate the prevalence of major depressive disorder (MDD) among spouses
      of men who use alcohol in two rural areas in Sri Lanka, and to examine whether
      the severity of alcohol-related problems (ARPs) in men and presence of alcohol
      related domestic violence are associated with MDD among these women. METHOD: In a
      cross-sectional study, ARPs among men were assessed using Alcohol Use Disorders
      Identification Test (AUDIT) questionnaire filled in by men, and domestic violence
      and husbands' drinking pattern data obtained from the women. MDD among the women
      was ascertained using the Structured Clinical Interview for DSM-IV Disorders for
      major depression. Using logistic regression we examined whether age, past history
      of depression, different indices of ARPs and domestic violence were associated
      with current MDD among the women. RESULTS: Point prevalence of MDD in the sample
      was 33.3% (95% CI: 25.93, 40.73%). Once adjusted for other factors, morning
      drinking of the spouse (odds ratio = 4.11, 95% CI: 1.25, 13.47; P = 0.019) and
      increasing age (odds ratio = 1.05, 95% CI: 1.01, 1.09; P = 0.003) significantly
      increased the odds of MDD. Being subjected to domestic violence/arguments also
      had a trend to be associated with MDD among women, but was not significant (odds
      ratio = 2.29, 95% CI: 0.95, 5.48; P = 0.062). CONCLUSION: The prevalence of MDD
      among spouses of men who use alcohol is markedly higher than that has been
      observed among Sri Lankan women in previous studies. The prevalence of MDD in
      women seems to increase when their husbands are morning drinkers, and with
      increasing age.

PMID- 25589091
TI  - The prevention and management of rabies.

PMID- 25589092
TI  - Narratives of HIV: measuring understanding of HIV and the law in HIV-positive
      patients.
AB  - OBJECTIVE: This study aimed to identify the understanding of people living with
      HIV and AIDS (PLWHA) regarding the application of the law around transmission of
      HIV in England and Wales. DESIGN: A questionnaire was designed to prompt
      participants attending a large HIV department to discuss their understanding of
      the law with reference to HIV transmission. The design focused on qualitative
      analysis as there were insufficient data available to inform a metric reflecting
      quantitative data on PLWHA's understanding of the legal implications of
      transmission. METHODS: The data were collected from PLWHA attending their HIV
      outpatient appointment to ensure relevance of population to the analysis. The
      answers were analysed using grounded theory and thematic analysis to identify key
      themes and theories for further testing. RESULTS: Analysis demonstrated that
      understanding of legal obligations and outcomes of prosecutions was poor and
      patchy, with behavioural restrictions often overstated. There was a strong theme
      of ownership of responsibility amongst PLWHA, and of reference to principles of
      morality beyond legal restrictions. CONCLUSIONS: PLWHA remain at risk of
      prosecution through poor understanding of the law. Clinical services and advocacy
      agencies should strive to increase understanding in order to enable PLWHA to
      comprehend the law and negotiate it successfully. This information should be
      shared as a process, not an isolated event.

PMID- 25589093
TI  - Clinical Characteristics and Outcome of Cardiovascular Implantable Electronic
      Device Infections in Turkey.
AB  - Infection is one of the most devastating outcomes of cardiovascular implantable
      electronic device (CIED) implantation and is related to significant morbidity and
      mortality. In our country, there is no evaluation about CIED infection.
      Therefore, our aim was to investigate clinical characteristics and outcome of
      patients who had infection related to CIED implantation or replacement. The study
      included 144 consecutive patients with CIED infection treated at 11 major
      hospitals in Turkey from 2005 to 2014 retrospectively. We analyzed the medical
      files of all patients hospitalized with the diagnosis of CIED infection.
      Inclusion criteria were definite infection related to CIED implantation,
      replacement, or revision. Generator pocket infection, with or without bacteremia,
      was the most common clinical presentation, followed by CIED-related endocarditis.
      Coagulase-negative staphylococci and Staphylococcus aureus were the leading
      causative agents of CIED infection. Multivariate analysis showed that infective
      endocarditis and ejection fraction were the strongest predictors of in-hospital
      mortality. 

PMID- 25589096
TI  - GPs are advised to cut back on extra work to defend core services.

PMID- 25589095
TI  - Oral toxicity of 3-nitro-1,2,4-triazol-5-one in rats.
AB  - 3-Nitro-1,2,4-triazol-5-one (NTO), an insensitive explosive, was evaluated to
      assess potential environmental and human health effects. A 14-day oral toxicity
      study in Sprague-Dawley rats was conducted with NTO in polyethylene glycol -200
      by gavage at doses of 0, 250, 500, 1000, 1500, or 2000 mg/kg-d. Body mass and
      food consumption decreased in males (2000 mg/kg-d), and testes mass was reduced
      at doses of 500 mg/kg-d and greater. Based on the findings in the 14-day study, a
      90-day study was conducted at doses of 0, 30, 100, 315, or 1000 mg/kg-d NTO.
      There was no effect on food consumption, body mass, or neurobehavioral
      parameters. Males in the 315 and 1000 mg/kg-d groups had reduced testes mass with
      associated tubular degeneration and atrophy. The testicular effects were the most
      sensitive adverse effect and were used to derive a benchmark dose (BMD) of 70
      mg/kg-d with a 10% effect level (BMDL10) of 40 mg/kg-d. 

PMID- 25589094
TI  - Advancing the science of measurement of diagnostic errors in healthcare: the
      Safer Dx framework.
AB  - Diagnostic errors are major contributors to harmful patient outcomes, yet they
      remain a relatively understudied and unmeasured area of patient safety. Although
      they are estimated to affect about 12 million Americans each year in ambulatory
      care settings alone, both the conceptual and pragmatic scientific foundation for
      their measurement is under-developed. Health care organizations do not have the
      tools and strategies to measure diagnostic safety and most have not integrated
      diagnostic error into their existing patient safety programs. Further progress
      toward reducing diagnostic errors will hinge on our ability to overcome
      measurement-related challenges. In order to lay a robust groundwork for
      measurement and monitoring techniques to ensure diagnostic safety, we recently
      developed a multifaceted framework to advance the science of measuring diagnostic
      errors (The Safer Dx framework). In this paper, we describe how the framework
      serves as a conceptual foundation for system-wide safety measurement, monitoring
      and improvement of diagnostic error. The framework accounts for the complex
      adaptive sociotechnical system in which diagnosis takes place (the structure),
      the distributed process dimensions in which diagnoses evolve beyond the doctor's
      visit (the process) and the outcomes of a correct and timely "safe diagnosis" as
      well as patient and health care outcomes (the outcomes). We posit that the Safer
      Dx framework can be used by a variety of stakeholders including researchers,
      clinicians, health care organizations and policymakers, to stimulate both
      retrospective and more proactive measurement of diagnostic errors. The feedback
      and learning that would result will help develop subsequent interventions that
      lead to safer diagnosis, improved value of health care delivery and improved
      patient outcomes. 

PMID- 25589098
TI  - Between the paper mills and the World Wide Web.

PMID- 25589097
TI  - The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen-Activated
      Protein Kinase Inhibitors.
AB  - The identification, synthesis, biological activity, and binding mode prediction
      of a series of pyrazolobenzothiazines as novel p38alpha MAPK inhibitors are
      reported. Some of these compounds showed interesting activity in both p38alpha
      MAPK and TNF-alpha release assays. Derivative 6 emerged as the most interesting
      compound with IC50 (p38alpha) = 0.457 MUm, IC50 (TNF-alpha) = 0.5 MUm and a
      promising kinase selectivity profile. The obtained results strongly indicate the
      pyrazolobenzothiazine core as a new p38alpha inhibitor chemotype worthy of future
      chemical optimization efforts directed toward identifying a new generation of
      anti-inflammatory agents. 

PMID- 25589099
TI  - [Seclusion--punishment or support?].

PMID- 25589100
TI  - [Paternalism on the rise?].

PMID- 25589101
TI  - [Re: Detection of cerebrospinal fluid leakage with tinted chlorhexidine].

PMID- 25589102
TI  - [Re: Detection of cerebrospinal fluid leakage with tinted chlorhexidine].

PMID- 25589103
TI  - [L.B. Karlsen and colleagues reply].

PMID- 25589104
TI  - [Re: The working environment continues to cause illness].

PMID- 25589105
TI  - [T.O.B. Aasen & J. Kongerud reply].

PMID- 25589106
TI  - [Re: The working environment continues to cause illness].

PMID- 25589110
TI  - [Re: Medication Reconciliation--important measure for better treatment].

PMID- 25589111
TI  - [S. Madsen and colleagues reply].

PMID- 25589112
TI  - [Re: Listening to patient preferences].

PMID- 25589113
TI  - [B. Gjelsvik replies].

PMID- 25589116
TI  - [Re: An integrated understanding of subjective disorders in clinical practice].

PMID- 25589117
TI  - [A. Tveramo and colleagues reply].

PMID- 25589118
TI  - [Re: Implementation of guidelines for PSA testing in general practice].

PMID- 25589120
TI  - "Ten commandments" for psychopharmacology.

PMID- 25589121
TI  - [Best treatment in nursing homes].

PMID- 25589122
TI  - [Guidelines or personal experience?].

PMID- 25589125
TI  - Compulsory hospitalisation in mental health care in Ostfold in 2000 and 2010.
AB  - BACKGROUND: For many years, it has been an objective of national public health
      policy in Norway to reduce the number of compulsory hospitalisations under the
      Norwegian Mental Health Care Act. Uncertain data quality and inadequate reporting
      have made it difficult to obtain reliable measurements of hospitalisation trends.
      We have examined changes in psychiatric emergency admissions and compulsory
      hospitalisations under the Mental Health Care Act between 2000 and 2010 in the
      county of Ostfold. MATERIAL AND METHOD: The material on which the study is based
      was gathered during two three-month periods - from 1 September to 30 November in
      the years 2000 and 2010 respectively. We compared emergency admissions in
      accordance with the national care quality indicator for compulsory
      hospitalisation in mental health care and examined whether there were changes in
      the diagnostic composition. RESULTS: The number of emergency admissions per 1,000
      population in Ostfold increased from a rate of 7.05 in 2000 to 8.86 in 2010 (p <
      0.001). There was no significant change in the rate of compulsory hospitalisation
      during this period, being 2.48 and 2.24 per 1,000 population, respectively. There
      was a sharp increase in the number of admissions for mental disorders related to
      alcohol and illicit drug abuse. INTERPRETATION: The study material showed that
      there was a significant increase in psychiatric emergency admissions between 2000
      and 2010. The rate of compulsory hospitalisation, measured among the population
      over the age of 18, remained unchanged during the period. The Norwegian Board of
      Health Supervision's care quality indicator for compulsory hospitalisation in
      mental health care can contribute to providing information and a basis of
      comparison for the use of compulsory hospitalisation, provided that the data
      submitted is quality assured. The highest increase was seen in the group of
      emergency admissions for mental disorders related to alcohol and illicit drug
      abuse as the principal diagnosis.

PMID- 25589126
TI  - [Seclusion in emergency psychiatry].
AB  - BACKGROUND: In Norway, seclusion (also called "shielding" or "open-area
      seclusion") is often used as an intervention in inpatient psychiatric wards as a
      continuation of milieu therapy, but the method remains controversial in health
      policy. A psychiatrist or occasionally a psychologist is responsible for making a
      decision on seclusion pursuant to Section 4-3 of the Mental Health Care Act.
      Because of the uncertainty regarding the content and academic legitimacy of this
      model, we have undertaken a review of available literature on the justification,
      practical application and effect of the Norwegian tradition of seclusion.
      MATERIAL AND METHOD: The article is based on systematic searches in national and
      international databases for the years 1930-2013. RESULTS: The seclusion method is
      closely associated with the development of psychiatric institutions, especially
      the establishment of emergency units and milieu therapy. The concept of seclusion
      covers a variety of approaches, and its knowledge base is generally poor.
      Clinical treatment studies are largely of older origin and most likely not
      descriptive of current practices. The absence of efficacy studies means that as
      of today, we have little knowledge on the benefits of using seclusion as
      treatment. INTERPRETATION: We detected a major discrepancy between the clinical
      ubiquity of the seclusion method and its knowledge basis. There is a clear need
      for more research on various types of seclusion to be able to assess the effects
      of seclusion in current practice.

PMID- 25589127
TI  - [Aortic aneurysm in a young woman].

PMID- 25589128
TI  - [How to prevent recurrent urinary tract infections after menopause?].

PMID- 25589129
TI  - [Asylum seekers on hunger strike--how far does the patient's right to refuse
      treatment go?].

PMID- 25589134
TI  - [Pregnant no asset].

PMID- 25589141
TI  - Photoluminescence-tunable carbon nanodots: surface-state energy-gap tuning.
AB  - The photoluminescence of carbon nanodots (C-dots) can be tuned by changing their
      surface chemistry or size because the photoluminescence is a function of the
      surface-state electronic transitions. Increasing the degree of surface oxidation
      leads to a narrowing of the energy gap of the surface; meanwhile, larger C-dots
      with an extensive pi-electron system, which can couple with surface electronic
      states, can also lead to a narrowing of the energy gap of the surface states. 

PMID- 25589142
TI  - We are all accountable for our professional actions.

PMID- 25589143
TI  - Antidepressant-like effects induced by NMDA receptor blockade and NO synthesis
      inhibition in the ventral medial prefrontal cortex of rats exposed to the forced
      swim test.
AB  - RATIONALE: Systemic treatment with NMDA receptor (NMDAR) antagonists, inhibitors
      of neuronal nitric oxide synthase (nNOS) or of soluble guanylyl cyclase (sGC),
      induce antidepressant-like effects in rats. Increased levels of glutamate and
      nitric oxide (NO) in the medial prefrontal cortex (MPFC) of stressed animals have
      been described in the literature. However, the role of the NMDAR-nNOS-sGC pathway
      of the MPFC in the mediation of forced swim-induced behaviors remains unclear.
      OBJECTIVE: The aim of this work was to test the hypothesis that the inhibition of
      the NMDAR-nNOS-sGC pathway in the ventral MPFC (infralimbic (IL) or prelimbic
      (PL)) would elicit antidepressant-like effects in the forced swim test (FST).
      METHODS: Rats implanted with cannulae aimed at the PL or the IL were exposed to
      the FST and injected with LY235959 (NMDAR antagonist), NPA (nNOS inhibitor), ODQ
      (sGC inhibitor), or carboxy-PTIO (NO scavenger). Additional groups received the
      AMPA antagonist, NBQX, before the effective doses of LY235959 or NPA. RESULTS:
      LY235959 administration into PL or IL before the FS pretest produced no effects.
      Administration of LY235959 (3 and 10 nmol/0.2 MUL) after pretest was effective
      only when administered into the PL. However, the administration of NPA (0.01
      nmol/0.2 MUL), c-PTIO (1.0 nmol/0.2 MUL), and ODQ (1.0 nmol/0.2 MUL) into the PL
      or IL before the FST produced antidepressant-like effects. NBQX blocked the
      antidepressant-like effect of LY235959 but not of NPA. CONCLUSION: Blocking NMDAR
      or NO signaling in the vMPFC, either in the IL or the PL, induces antidepressant
      like effects in the rat FST. These effects seemingly occur through independent
      mechanisms, since NBQX blocked the former effect but not the latter.

PMID- 25589146
TI  - Neuroleptic malignant syndrome and the catatonic dilemma.

PMID- 25589144
TI  - Age-dependent changes in cocaine sensitivity across early ontogeny in male and
      female rats: possible role of dorsal striatal D2(High) receptors.
AB  - RATIONALE: Responsiveness to acute psychostimulant administration varies across
      ontogeny. OBJECTIVE: The purpose of the present study was to determine if age
      dependent changes in D2(High) receptors may be responsible for the ontogeny of
      cocaine sensitivity in preweanling, adolescent, and adult rats. METHODS: [(3)H]
      Domperidone/dopamine competition assays were used to determine ontogenetic
      changes in the proportion of D2(High) receptors in male and female preweanling
      [postnatal day (PD) 5, 10, 15, and 20], adolescent (PD 40), and adult (PD 80)
      rats. In the behavioral experiment, responsiveness to cocaine (2.5, 5, 10, or 20
      mg/kg) was assessed on PD 20, PD 40, and PD 80 for 60 min. Male and female rats
      were habituated to the apparatus on the 2 days prior to testing. Distance
      traveled data were presented both untransformed and as percent of saline
      controls. RESULTS: Male and female preweanling rats (PD 5-PD 20) had a
      significantly greater percentage of dorsal striatal D2(High) receptors than
      adolescent or adult rats. Likewise, preweanling rats (PD 20) were more sensitive
      to the behavioral effects of cocaine than the two older age groups. Adolescent
      and adult rats responded in a generally similar manner; however, analysis of the
      untransformed locomotor activity data suggested that adolescent rats were
      hyporesponsive to 2.5 and 20 mg/kg cocaine when compared to adults. CONCLUSIONS:
      Data from the present study are consistent with the hypothesis that ontogenetic
      changes in D2(High) receptors are responsible for age-dependent differences in
      psychostimulant sensitivity.

PMID- 25589145
TI  - Nucleus accumbens AMPA receptor involvement in cocaine-conditioned place
      preference under different dietary conditions in rats.
AB  - RATIONALE: When ad libitum-fed (AL) rats undergo cocaine place preference
      conditioning (CPP) but are switched to food restriction (FR) for testing, CPP is
      enhanced and preference scores correlate with phosphorylation of alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 at Ser845 in
      nucleus accumbens (NAc) core. OBJECTIVES: The present study tested whether a
      similar association exists in AL rats and whether an inhibitor of Ca(2+)
      permeable AMPARs blocks CPP expression in either diet group. MATERIALS AND
      METHODS: In experiments 1-3, AL rats were conditioned with cocaine (12.0 mg/kg,
      i.p.). Three weeks later, CPP was tested daily and brains were harvested after
      the fifth test. Western analyses were used to probe for levels of AMPA receptors
      in NAc. In experiment 4, AL rats were conditioned, half were switched to FR for
      testing, and half in each diet group received NAc core microinjection of 1
      naphthylacetyl spermine (NASPM (NASPM) (25.0 MUg) prior to each test. RESULTS: In
      experiment 1, CPP expression in AL rats was associated with elevated pSer845
      GluA1, GluA1, and GluA2 in NAc. In experiment 2, the correlation between pSer845
      GluA1 and CPP was localized to NAc core. In experiment 3, pSer845-GluA1 following
      a CPP test was higher in NAc synaptic membranes of FR relative to AL rats. In
      experiment 4, NASPM blocked CPP expression in both diet groups. CONCLUSIONS:
      Results support a scheme in which pSer845-GluA1 in NAc core underlies expression
      of cocaine CPP and does so by stabilizing or trafficking Ca(2+)-permeable AMPARs
      to the synaptic membrane. The more robust CPP of FR rats may result from
      upregulation of stimulus-induced pSer845-GluA1.

PMID- 25589147
TI  - Incidence and identification of inadvertent lumbar vein catheterisation in the
      NICU.

PMID- 25589148
TI  - Tadehaginoside modulates lipogenesis and glucose consumption in HepG2 cells.
AB  - Tadehaginoside (TS) is a phenylpropanoid glycoside found in Tadehagi triquetrum,
      a medicinal plant with multiple biological activities. This study investigated
      the effect of TS on lipogenesis and glucose consumption in HepG2 cells. Treatment
      with TS inhibited lipid accumulation in a dose-dependent manner. This inhibition
      was closely associated with the downregulation of lipogenic genes such as SREBP
      1a, SREBP-2 and their downstream targets (FAS, ACC, HMGR) and the upregulation of
      lipolytic gene PPARalpha as revealed by real-time quantitative PCR. Further
      investigation showed that TS significantly stimulated glucose consumption by
      HepG2 cells and glucose uptake by C2C12 myotubes, which could be partially
      explained by the upregulation of PPARgamma. Collectively, these results clearly
      indicate that TS is an effective regulator of lipogenesis and glucose
      consumption, which could be useful in treatment of obesity and diabetes. 

PMID- 25589149
TI  - The role of the body in end-stage kidney disease in young adults: Gender, peer
      and intimate relationships.
AB  - OBJECTIVES: To understand how the physical body, and changes in the physical
      body, influence peer and intimate relationships and parenting in young adults on
      renal replacement therapies (RRT). METHODS: Qualitative interview data from 40
      young adults aged 16-30 years with end-stage kidney disease (ESKD), first
      diagnosed aged 0-19 years, were analysed using modified grounded theory.
      FINDINGS: Alternating modalities of RRT had a 'yo-yo' effect on the bodies of
      interviewees, repeatedly reconstructing them as either 'transplanted' bodies,
      often initially obese, or as 'dialysis' bodies', often underweight. Invisible
      somatic changes had a major impact on gendered social identity, making intimate
      social relationships and parenthood problematic. Prepubertal onset interviewees
      were generally less successful in forming partnerships than those with
      postpubertal onset; and interviewees on dialysis were likely to postpone
      partnering until they were transplanted. Social networks were essential for
      finding a partner, but male interviewees had fewer networks than females.
      Parenthood was particularly challenging for female interviewees. CONCLUSIONS: In
      ESKD, life-saving RRT brings major changes to the body. These adversely affect
      social relationships and family formation during the crucial period of early
      adulthood. Effects vary according to age of onset, RRT modality, and gender, with
      those who were ill before puberty and those on dialysis worst affected.

PMID- 25589150
TI  - State level variations in nephrology workforce and timing and incidence of
      dialysis in the United States among children and adults: a retrospective cohort
      study.
AB  - BACKGROUND: Multiple factors influence timing of dialysis initiation. The impact
      of supply of nephrology workforce on timing and incidence of dialysis initiation
      is not well known. METHODS: We determined the number of pediatric and adult
      nephrologists in each state using data from the American Medical Association and
      American Boards of Internal Medicine and Pediatrics. We ascertained state
      population data from the 2010 US Census. United States Renal Data System (USRDS)
      data were used to determine estimated glomerular filtration rate (eGFR) at
      dialysis initiation and dialysis incidence for adults (>=18 years) in 2008 and
      children (<18 years) in 2007-2009 by state. RESULTS: Across all states, there
      were a median of 3.0 (IQR 2.3 to 3.4) adult nephrologists per 100,000 adults and
      0.5 (IQR 0.2 to 0.9) pediatric nephrologists per 100,000 children. The median
      eGFR at start of dialysis was 9.8 mL/min/1.73 m2 (IQR 7.1-13.1) in adults and 8.5
      mL/min/1.73 m2 (IQR 6.2-11.4) in children. Neither the number of adult (Spearman
      r of 0.02 [95% CI -0.26-0.30], p = 0.88) nor pediatric (Spearman r of -0.13 [95% 
      0.39-0.15], p = 0.38) nephrologists per state population was associated with mean
      eGFR across states. The number of nephrologists per state population was
      associated with incident dialysis cases per state population in adults (Spearman
      r of 0.50 [95% CI 0.26-0.68], p = 0.0002), but not in children (Spearman r of 
      0.06 [95% CI -0.33-0.22], p = 0.67). In linear regression models, the association
      between nephrologists per state population and incident dialysis cases per state
      population remained statistically significant (p = 0.006) after adjustment for
      provider characteristics. CONCLUSIONS: Nephrology workforce supply is aligned
      with demand but does not appear to be associated with timing of dialysis
      initiation.

PMID- 25589151
TI  - Prospective trial of breast MRI versus 2D and 3D ultrasound for evaluation of
      response to neoadjuvant chemotherapy.
AB  - BACKGROUND: Preoperative imaging to assess response to neoadjuvant chemotherapy
      in breast cancer is routine but no single imaging modality is standard of
      practice. Our hypothesis is that ultrasound (US) is comparable to magnetic
      resonance imaging (MRI) in the prediction of residual disease. METHODS: A single
      institution, Institutional Review Board-approved prospective trial of primary
      invasive ductal breast cancer patients receiving neoadjuvant chemotherapy
      enrolled women from 2008 to 2012. Two-dimensional (2D) and three-dimensional (3D)
      US, as well as MRI images of pre- and post-neoadjuvant tumors were obtained. Skin
      involvement or inadequate images were excluded. Residual tumor on imaging was
      compared with surgical pathology. Differences of tumor volume on imaging and
      pathology were compared using the non-parametric Wilcoxon signed-rank test. US to
      MRI agreement was determined by the kappa coefficient. Tumor volumes in estrogen
      receptor (ER), progesterone receptor (PR), and Her2neu subgroups were compared
      using the Kruskal-Wallis test. ER/PR staining <5 % was considered negative;
      Her2neu status was determined by in situ hybridization. RESULTS: Forty-two
      patients were enrolled in the study; 39 had evaluable post-treatment data. Four
      patients were Her2neu positive, and 17 (46 %) patients had triple-negative
      tumors. Among 11 (28 %) patients with pathologic complete response (pCR), US
      correctly predicted pCR in six (54.5 %) patients compared with eight (72.7 %)
      patients when MRI was used. This is a substantial agreement between US and MRI in
      predicting pCR (kappa = 0.62). There was no difference between 2D and 3D US
      modalities. For the 39 patients, US and MRI had no significant difference in
      volume estimation of pathology, even stratified by receptor status. CONCLUSION:
      The estimation of residual breast tumor volume by US and MRI achieves similar
      results, including prediction of pCR.

PMID- 25589152
TI  - Incorporation of radiotherapy in the multidisciplinary treatment of isolated
      retroperitoneal lymph node recurrence from colorectal cancer.
AB  - PURPOSE: This article was designed to study the clinical outcomes and prognostic
      factors following radiotherapy (RT) in the multidisciplinary management of
      isolated retroperitoneal lymph node (RPLN) recurrence of colorectal cancer.
      METHODS: We identified 52 patients treated consecutively with tumor-directed RT
      for isolated RPLN recurrence. Twenty-five patients received upfront RT (Group 1).
      Twenty-seven patients received RT after systemic therapy. The deferred RT was
      administered either to locally controlled tumors (Group 2, n = 17) or to locally
      progressive tumors in RPLNs (Group 3, n = 10). RESULTS: The median overall
      survival and progression-free survival were 41 and 13 months, respectively, with
      a median follow-up time of 34 months. Survival was not significantly different
      among three groups. Local recurrence (32/52) was predominant and occurred earlier
      than distant metastasis (31/52). Two-thirds of the local recurrences (21/32)
      involved outfield recurrence, which was mostly in the cranial direction (15/21)
      from the upper margin of the RT volume. Repeated RT successfully salvaged a
      substantial number of patients. A shorter disease-free interval, low-dose
      radiation, and a tumor location above the renal vein were independent risk
      factors for local recurrence (all P < 0.05). A large gross tumor volume was an
      independent risk factor for distant metastasis (P = 0.037). No acute or late RT
      related toxicity >= grade 3 occurred. CONCLUSIONS: Our analysis suggests that
      both upfront RT and deferred RT incorporated into multidisciplinary management
      are potentially effective treatment strategies. We found that gross tumor volume,
      tumor location, and disease-free interval are important prognostic factors and
      should be taken into consideration to decide the timing of RT.

PMID- 25589153
TI  - High levels of anomalous self-experience are associated with longer duration of
      untreated psychosis.
AB  - AIM: To investigate the relationship between anomalous self-experiences and
      duration of untreated psychosis in a sample of patients with first-episode
      schizophrenia spectrum disorders. METHODS: Anomalous self-experiences were
      assessed by means of the Examination of Anomalous Self-Experience manual in 55
      patients referred to their first adequate treatment for schizophrenia. Diagnoses,
      symptom severity, functioning and childhood trauma were assessed using the
      Structured Clinical Interview for the Positive and Negative Syndrome Scale,
      Premorbid Adjustment Scale, Social Functioning Scale and Childhood Trauma
      Questionnaire. Substance misuse was measured with the Drug Use Disorder
      Identification Test, and alcohol use was measured with the Alcohol Use Disorder
      Identification Test. Duration of untreated psychosis was measured in accordance
      with a standardized procedure. RESULTS: High levels of anomalous self-experiences
      are significantly associated with longer duration of untreated psychosis, an
      association which held after correcting for other variables associated with long
      duration of untreated psychosis. CONCLUSIONS: The field of early detection in
      psychosis is in need of additional clinical perspectives to make further
      progress. Improved understanding and assessment of anomalous self-experiences may
      help clinicians to detect these important phenomena and provide earlier help, and
      thus reduce treatment delay.

PMID- 25589154
TI  - Surgery under general anaesthesia in severe hidradenitis suppurativa: a study of
      363 primary operations in 113 patients.
AB  - BACKGROUND: Treatment of hidradenitis suppurativa (HS) is a difficult
      undertaking, especially as there is no consensus on what surgical technique is
      preferred. At our centre severe HS (Hurley II/III) is operated under general
      anaesthesia, mostly with the STEEP procedure. OBJECTIVES: To investigate
      characteristics, surgical outcomes and patient satisfaction of HS patients who
      underwent deroofing or STEEP under general anaesthesia. METHODS: A clinical
      records-based retrospective analysis was conducted of all patients who had
      surgery under general anaesthesia between 1999 and 2013. Patient satisfaction was
      retrospectively investigated with questionnaires. RESULTS: A total of 482
      operations (363 primary operations and 119 re-operations) were performed during
      the study period. The proportion of women in the included population was 68%. The
      median diagnostic delay (patient's and doctor's delay) was 6.5 years. Relapses
      occurred after 29.2% of primary operations. Women had higher relapse rates than
      men [odds ratio 2.85 (1.07;7.61)]. Hypergranulation of the wound was the most
      common complication and occurred in 7% of all operations. The median score
      patients attributed to the medical effect of surgery was eight of 10 (zero
      corresponding to very dissatisfied and 10 to very satisfied). CONCLUSION: The
      diagnostic delay in HS is long due to a lack of knowledge in both patients and
      health care professionals, indicating that there is a need for education.
      Deroofing and the STEEP are effective surgical procedures in severe cases of HS
      and lead to a relatively high patient satisfaction. The postoperative relapse
      risk is higher in women. Prospective studies are required for the development of
      clear guidelines on the appropriate choice of surgery.

PMID- 25589156
TI  - A molecular view of the role of chirality in charge-driven polypeptide
      complexation.
AB  - Polyelectrolyte molecules of opposite charge are known to form stable complexes
      in solution. Depending on the system conditions, such complexes can be solid or
      liquid. The latter are known as complex coacervates, and they appear as a second
      liquid phase in equilibrium with a polymer-dilute aqueous phase. This work
      considers the complexation between poly(glutamic acid) and poly(lysine), which is
      of particular interest because it enables examination of the role of chirality in
      ionic complexation, without changes to the overall chemical composition.
      Systematic atomic-level simulations are carried out for chains of poly(glutamic
      acid) and poly(lysine) with varying combinations of chirality along the backbone.
      Achiral chains form unstructured complexes. In contrast, homochiral chains lead
      to formation of stable beta-sheets between molecules of opposite charge, and
      experiments indicate that beta-sheet formation is correlated with the formation
      of solid precipitates. Changes in chirality along the peptide backbone are found
      to cause "kinks" in the beta-sheets. These are energetically unfavorable and
      result in irregular structures that are more difficult to pack together. Taken
      together, these results provide new insights that may be of use for the
      development of simple yet strong bioinspired materials consisting of beta-rich
      domains and amorphous regions. 

PMID- 25589155
TI  - Sertraline and breastfeeding: review and meta-analysis.
AB  - We examined the risk-benefit profile of sertraline treatment during
      breastfeeding, summarized the available literature on sertraline use, presented
      previously unpublished data, and performed a correlation-based meta-analysis of
      sertraline serum levels in mother-infant pairs. We conducted a search of PubMed
      and the National Library of Medicine LactMed database. We performed a meta
      analysis to examine correlations between maternal and infant serum sertraline
      levels in the existing literature and in previously unpublished data. Of 167
      available infant sertraline levels, 146 (87.4 %) were below the limit of
      detection, and the meta-analysis found no significant relationship between
      maternal and infant sertraline concentrations. Of 150 infant desmethylsertraline
      levels, 105 (70.0 %) were below the limit of detection. The correlation analysis
      revealed a significant relationship between maternal and infant
      desmethylsertraline concentrations, but this metabolite has only a fraction of
      the activity of sertraline. A significant relationship was also found for the sum
      of sertraline and desmethylsertraline, which stems primarily from the
      contribution of desmethylsertraline. Sertraline is a first-line drug for
      breastfeeding women due to documented low levels of exposure in breastfeeding
      infants and very few adverse events described in case reports. Based on the
      current literature, neither routine serum sampling nor genotyping is warranted
      for breastfeeding mothers taking sertraline and/or their infants. Routine
      pediatric care is appropriate monitoring for breastfed infants of women who take
      sertraline monotherapy. 

PMID- 25589157
TI  - Nano/micro hybrid scaffold of PCL or P3HB nanofibers combined with silk fibroin
      for tendon and ligament tissue engineering.
AB  - A novel biodegradable nano/micro hybrid structure was obtained by electrospinning
      P3HB or PCL nanofibers onto a twisted silk fibroin (SF) structure, with the aim
      of fabricating a suitable scaffold for tendon and ligament tissue engineering.
      The electrospinning (ES) processing parameters for P3HB and PCL were optimized on
      2D samples, and applied to produce two different nano/micro hybrid constructs
      (SF/ES-PCL and SF/ES-P3HB).Morphological, chemico-physical and mechanical
      properties of the novel hybrid scaffolds were evaluated by SEM, ATR FT-IR, DSC,
      tensile and thermodynamic mechanical tests. The results demonstrated that the
      nanofibers were tightly wrapped around the silk filaments, and the crystallinity
      of the SF twisted yarns was not influenced by the presence of the electrospun
      polymers. The slightly higher mechanical properties of the hybrid constructs
      confirmed an increase of internal forces due to the interaction between nano and
      micro components. Cell culture tests with L929 fibroblasts, in the presence of
      the sample eluates or in direct contact with the hybrid structures, showed no
      cytotoxic effects and a good level of cytocompatibility of the nano/micro hybrid
      structures in term of cell viability, particularly at day 1. Cell viability onto
      the nano/micro hybrid structures decreased from the first to the third day of
      culture when compared with the control culture plastic, but appeared to be higher
      when compared with the uncoated SF yarns. Although additional in vitro and in
      vivo tests are needed, the original fabrication method here described appears
      promising for scaffolds suitable for tendon and ligament tissue engineering. 

PMID- 25589158
TI  - Microleakage of bacteria in different implant-abutment assemblies: an in vitro
      study.
AB  - PURPOSE: The aim of the present in vitro study was to evaluate the leakage
      observed for 2 different microbial species at the level of the implant-abutment
      (I-A) interface, and the marginal fit and size of microgap at the I-A interface
      in 2 different implant connections. METHODS: Ten specimens of each group were
      tested. The inner parts of 5 implants per group were inoculated with 0.1 MUL of a
      viable Enterococcus faecalis suspension and 5 implants per group with
      Aggregatibacter actinomycetemcomitans. All of the vials containing the control
      specimens were incubated at 37 degrees C under aerobic condition for E. faecalis
      and 37 degrees C in presence of 5% CO2 for A. actinomycetemcomitans. They were
      maintained for 14 days, and the possible penetration of bacterial suspension into
      the surrounding solution was determined by the observation of turbidity of the
      broth. The I-A interface was evaluated for size of microgap and measured under
      SEM. Five implants of each group were evaluated. The marginal fit between implant
      and abutment was measured at 8 random locations in each assembly, under different
      magnifications at the interface. RESULTS: No leakages through the I-A interface
      were demonstrated for either type of connection evaluated. The microgap values of
      all I-A interfaces ranged from 0.008 to 2.009 MUm; the differences between the 2
      systems were statistically significant. CONCLUSIONS: The present study
      demonstrated that a good marginal fit of implant components seemed to be able to
      prevent bacterial leakage.

PMID- 25589159
TI  - Local blood flow patterns in stented coronary bifurcations: an experimental and
      numerical study.
AB  - PURPOSE: Despite the atheroprone environment of blood flow in coronary
      bifurcations, limited quantitative information is available on the hemodynamics
      occurring in these geometries, both before and after their treatment with
      endovascular stents. Previous studies have focused on computational fluid
      dynamics (CFD) analyses and have bypassed the challenges associated with
      experimentally representing the flow environment, providing no means for
      validation. This study analyzed steady flow conditions in 3 bifurcation angles
      and 4 different single- and double-stenting procedures, which are used clinically
      in coronary bifurcations. METHODS: The numerical aspect of this study utilized
      geometries derived from CAD models (nonstented cases) and finite element
      simulations (stented cases). Digital particle image velocimetry (DPIV) testing
      was conducted within compliant bifurcating models for which an uncertainty
      analysis was performed at each measurement location for CFD validation purposes.
      Results were analyzed in terms of velocity magnitude contour maps and axial
      velocity profiles at several locations in the bifurcated vessels. RESULTS AND
      CONCLUSIONS: Qualitatively, the 2 approaches showed agreement in the bulk flow
      patterns. However, the velocity computed with CFD was outside the DPIV
      uncertainty estimates, which can be attributed to the intrinsic difference and
      modeling assumptions of the 2 approaches. The findings reveal that wider
      bifurcation angles and double-stenting procedures are both characterized by
      increased areas of low flow and recirculation. Additionally, inferior performance
      in terms of viscous and wall shear stresses was observed in double-stented cases.

PMID- 25589160
TI  - The efficacy of custom-made porous hydroxyapatite prostheses for cranioplasty:
      evaluation of postmarketing data on 2697 patients.
AB  - PURPOSE: Cranioplasty is a surgical intervention aimed at reestablishing the
      integrity of skull defects. Autologous bone is still considered the treatment of
      choice for cranioplasty. The aims of this study were to characterize and evaluate
      the efficacy of porous hydroxyapatite (HA) to fill skull defects based on its
      biomimetic characteristics. METHODS: The authors analyzed the postmarketing data
      of all patients treated with custom-made porous HA prostheses (CustomBone
      Service). Characterization data in terms of physicochemical analysis and
      mechanical performance of the porous HA prostheses were also reported. RESULTS:
      The low incidence of adverse events (5.72%) due to the use of HA porous custom
      made prostheses for cranioplasty is related to the biomimetic performance of the
      prostheses. The composition and morphology of the porosity enable it to be a
      useful biomimetic prosthesis for the reconstruction of large and complex skull
      defects, also able to promote osteointegration. CONCLUSIONS: These collected and
      analyzed data demonstrate that porous HA is a suitable material to produce custom
      made prostheses to repair craniolacunia. It is a biomimetic implant well
      tolerated in both adult and pediatric patients and has been shown to be an
      effective and good alternative for cranial reconstruction.

PMID- 25589161
TI  - Synthetic, potentiometric and spectroscopic studies of chelation between Fe(III)
      and 2,5-DHBA supports salicylate-mode of siderophore binding interactions.
AB  - Catecholate type enterobactin, a prototype siderophore, comprises 2,3
      dihydroxybenzoic acid (2,3-DHBA) cyclically linked to serine in E. coli. The
      existence of iron-chelating ligands in humans is a recent discovery, however, the
      basic chemical interactions between 2,5-dihydroxybenzoic acid and Fe(III) ion
      remain poorly understood. Achieving an accurate description of the fundamental
      Fe(III) binding properties of 2,5-DHBA is essential for understanding its role in
      iron transport mechanisms. Here, we show that 2,5-DHBA binds iron in a salicylate
      mode via a two-step kinetic mechanism by UV spectroscopy. Complexation between
      Fe(III) salt and 2,5-DHBA initially occurs at 1:1 ratio (of ligand to metal) and
      binding resulting in higher-order complexes continues at higher concentrations.
      Through potentiometric measurements we quantify the distribution of Fe(III)-2,5
      DHBA complexes with 1:1, 1:2 and 1:3 stoichiometry. The formation of 1:3
      complexes is further supported through high-resolution mass spectrometry.
      Further, using kinetic and equilibrium UV spectroscopy, we report Fe(III)-2,5
      DHBA complex formation at a pH range of 2.5-9.0 at 298.15K in water. Maximum
      complexation occurred at a pH range of 4.5-6.5 consistent with deprotonation of
      the carboxylic acid proton. Equilibrium measurements and stopped-flow kinetics
      show that complexation rate constants were independent of concentrations of 2,5
      DHBA. Together the data supports a model in which the rate-determining step
      involves rearrangement of ligands on an initial complex formed by reversible
      binding between the carboxylate group of 2,5-DHBA and Fe(III). 

PMID- 25589162
TI  - Dietary protein influences the life-history characteristics across generations in
      the African striped mouse Rhabdomys.
AB  - The level of dietary protein determines the onset of reproduction, affects
      offspring growth and maturation, and hence influences life-history traits and
      fitness. However, to date, the long-term life-history consequences of protein
      deficiency are not well understood. We studied the transgenerational effects of
      different levels of dietary protein on the life-history and level of maternal
      behavior of the striped mouse Rhabdomys dilectus chakae in captivity. Breeding
      pairs were assigned to three treatments based on the percentage of dietary
      protein: baseline (BP; 19%); high protein (HP; 24%); and low protein (LP; 10%).
      Reproductive output and offspring ontogeny was diminished in the LP treatment
      compared to the other treatments. Transgenerational effects were studied by
      breeding F2 females raised on the LP or HP diets on the same (HP-HP, LP-LP) or
      altered diets (HP-LP, LP-HP). The LP-LP treatment had no reproductive success,
      while reproductive capacity in the remaining treatments was determined mainly by
      the diet of mothers at breeding. Pups from protein-restricted females (LP, HP-LP)
      showed post-weaning compensatory growth. Timing of sexual maturity was age
      dependent in female and mass-dependent in male offspring. Females fed low protein
      diets during breeding (LP, HP-LP) displayed lower levels of maternal behavior
      than females from the other treatments. This study demonstrates that the level of
      dietary protein influences the life-history of R. d. chakae in predictable ways.
      The taxon responds to changes in dietary protein at breeding, largely regardless
      of its nutrition during rearing. Such phenotypic flexibility in life-history
      parameters allows Rhabdomys to adaptively respond to unpredictable environmental
      changes.

PMID- 25589164
TI  - Novel oral anticoagulants and valvular atrial fibrillation: are they always
      contraindicated?
AB  - Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia, and is
      associated with an increased risk of death, stroke, and other thromboembolic
      events. Valvular heart disease (VHD) frequently coexists with AF, mostly in
      elderly patients. After the introduction of novel oral anticoagulants (NOACs)
      approved for the prevention of stroke in non-valvular atrial fibrillation (NVAF)
      on the basis of recent trials, the importance of a universal definition of NVAF
      was raised in clinical practice. In the most recent guidelines, the term valvular
      AF is used to imply that AF is related to rheumatic valvular disease
      (predominantly mitral stenosis), or prosthetic heart valves. In all the trials
      comparing NOACs and warfarin, a significant percentage of patients presented any
      type of VHD, excluding rheumatic mitral stenosis and mechanical heart valve. The
      subgroups analysis performed, so far showed no significant differences in terms
      of efficacy in the VHD subgroup compared to the general AF population. A
      restrictive definition of valvular AF (i.e., rheumatic mitral stenosis and
      mechanical heart valve) seems to be the most appropriate to contraindicate
      treatment with NOACs for AF thromboprophylaxis. In the remaining AF patients with
      significant valvular disease who per se would not require oral anticoagulation,
      NOACs should be allowed. 

PMID- 25589165
TI  - Aortic dissection and stroke in a 37-year-old woman: discovering an emerging
      heritable connective tissue disorder.

PMID- 25589166
TI  - Do clinicians decide relying primarily on Bayesian principles or on Gestalt
      perception? Authors' reply.

PMID- 25589163
TI  - Transcript profiling of different types of multiple sclerosis lesions yields FGF1
      as a promoter of remyelination.
AB  - Chronic demyelination is a pathological hallmark of multiple sclerosis (MS). Only
      a minority of MS lesions remyelinates completely. Enhancing remyelination is,
      therefore, a major aim of future MS therapies. Here we took a novel approach to
      identify factors that may inhibit or support endogenous remyelination in MS. We
      dissected remyelinated, demyelinated active, and demyelinated inactive white
      matter MS lesions, and compared transcript levels of myelination and inflammation
      related genes using quantitative PCR on customized TaqMan Low Density Arrays. In
      remyelinated lesions, fibroblast growth factor (FGF) 1 was the most abundant of
      all analyzed myelination-regulating factors, showed a trend towards higher
      expression as compared to demyelinated lesions and was significantly higher than
      in control white matter. Two MS tissue blocks comprised lesions with adjacent de-
      and remyelinated areas and FGF1 expression was higher in the remyelinated rim
      compared to the demyelinated lesion core. In functional experiments, FGF1
      accelerated developmental myelination in dissociated mixed cultures and promoted
      remyelination in slice cultures, whereas it decelerated differentiation of
      purified primary oligodendrocytes, suggesting that promotion of remyelination by
      FGF1 is based on an indirect mechanism. The analysis of human astrocyte responses
      to FGF1 by genome wide expression profiling showed that FGF1 induced the
      expression of the chemokine CXCL8 and leukemia inhibitory factor, two factors
      implicated in recruitment of oligodendrocytes and promotion of remyelination.
      Together, this study presents a transcript profiling of remyelinated MS lesions
      and identified FGF1 as a promoter of remyelination. Modulation of FGF family
      members might improve myelin repair in MS. 

PMID- 25589167
TI  - Development of a walleye cell line and use to study the effects of temperature on
      infection by viral haemorrhagic septicaemia virus group IVb.
AB  - A cell line, WE-cfin11f, with a fibroblast-like morphology was developed from a
      walleye caudal fin and used to study the intersection of thermobiology of
      walleye, Sander vitreus (Mitchill), with the thermal requirements for replication
      of viral haemorrhagic septicaemia virus (VHSV) IVb. WE-cfin11f proliferated from
      10 to 32  degrees C and endured as a monolayer for at least a week at 1-34 
      degrees C. WE-cfin11f adopted an epithelial shape and did not proliferate at 4 
      degrees C. Adding VHSV IVb to cultures at 4 and 14  degrees C but not 26  degrees
      C led to cytopathic effects (CPE) and virus production. At 4  degrees C, virus
      production developed more slowly, but Western blotting showed more N protein
      accumulation. Infecting monolayer cultures at 4  degrees C for 7 days and then
      shifting them to 26  degrees C resulted in the monolayers being broken in small
      areas by CPE, but with time at 26  degrees C, the monolayers were restored. These
      results suggest that at 26  degrees C, the VHSV IVb life cycle stages responsible
      for CPE can be completed, but the production of virus and the initiation of
      infections cannot be accomplished. 

PMID- 25589169
TI  - C-C coupling of ketones with methanol catalyzed by a N-heterocyclic carbene
      phosphine iridium complex.
AB  - An N-heterocyclic carbene-phosphine iridium complex system was found to be a very
      efficient catalyst for the methylation of ketone via a hydrogen transfer
      reaction. Mild conditions together with low catalyst loading (1 mol %) were used
      for a tandem process which involves the dehydrogenation of methanol, C=C bond
      formation with a ketone, and hydrogenation of the new generated double bond by
      iridium hydride to give the alkylated product. Using this iridium catalyst
      system, a number of branched ketones were synthesized with good to excellent
      conversions and yields.

PMID- 25589168
TI  - New mass-spectrometry-compatible degradable surfactant for tissue proteomics.
AB  - Tissue proteomics is increasingly recognized for its role in biomarker discovery
      and disease mechanism investigation. However, protein solubility remains a
      significant challenge in mass spectrometry (MS)-based tissue proteomics.
      Conventional surfactants such as sodium dodecyl sulfate (SDS), the preferred
      surfactant for protein solubilization, are not compatible with MS. Herein, we
      have screened a library of surfactant-like compounds and discovered an MS
      compatible degradable surfactant (MaSDeS) for tissue proteomics that solubilizes
      all categories of proteins with performance comparable to SDS. The use of MaSDeS
      in the tissue extraction significantly improves the total number of protein
      identifications from commonly used tissues, including tissue from the heart,
      liver, and lung. Notably, MaSDeS significantly enriches membrane proteins, which
      are often under-represented in proteomics studies. The acid degradable nature of
      MaSDeS makes it amenable for high-throughput MS-based proteomics. In addition,
      the thermostability of MaSDeS allows for its use in experiments requiring high
      temperature to facilitate protein extraction and solubilization. Furthermore, we
      have shown that MaSDeS outperforms the other MS-compatible surfactants in terms
      of overall protein solubility and the total number of identified proteins in
      tissue proteomics. Thus, the use of MaSDeS will greatly advance tissue proteomics
      and realize its potential in basic biomedical and clinical research. MaSDeS could
      be utilized in a variety of proteomics studies as well as general biochemical and
      biological experiments that employ surfactants for protein solubilization. 

PMID- 25589170
TI  - Work extraction from heat-powered quantized optomechanical setups.
AB  - We analyze work extraction from an autonomous (self-contained) heat-powered
      optomechanical setup. The initial state of the quantized mechanical oscillator
      plays a key role. As the initial mean amplitude of the oscillator decreases, the
      resulting efficiency increases. In contrast to laser-powered self-induced
      oscillations, work extraction from a broadband heat bath does not require
      coherence or phase-locking: an initial phase-averaged coherent state of the
      oscillator still yields work, as opposed to an initial Fock-state. 

PMID- 25589171
TI  - Application of the combination index integrated with confidence intervals to
      study the toxicological interactions of antibiotics and pesticides in Vibrio
      qinghaiensis sp.-Q67.
AB  - It is necessary to explore the effect of confidence intervals on the combination
      index (CI) so that rationally evaluate the toxicological interaction (synergism
      or antagonism) which is dependent on the concentration ratio, the mixture
      concentration and the exposure time. To effectively detect the toxicological
      interaction taking place in mixtures, we combined the CI with the observation
      based confidence intervals (OCI) which can characterize the uncertainty in
      toxicity test and in data fitting. In time scale, the short-term (15min) and long
      term (12h) toxicities of three chemicals (imidacloprid (IMI), pirimicarb (PIR)
      and streptomycin sulfate (STR)) and their binary mixtures on Vibrio qinghaiensis
      sp.-Q67 were determined by the microplate toxicity analysis (MTA). The mixtures
      of IMI, PIR and STR have additive actions all but four IMI-PIR rays (R2-R5) at
      the effect levels above about 30-40% whose long-term toxicological interaction
      are synergism. 

PMID- 25589172
TI  - Effect of COX-2 inhibitors and other non-steroidal inflammatory drugs on breast
      cancer risk: a meta-analysis.
AB  - Evidence on non-steroidal anti-inflammatory drugs (NSAID) use and breast cancer
      risk shows a slightly protective effect of these drugs, but previous studies lack
      randomized clinical trial results and present high heterogeneity in exposure
      measurement. This systematic review and meta-analysis widens the knowledge about
      NSAID use and breast cancer risk, updating the information from the last meta
      analysis, focusing on evidence on specific effects of COX-2 inhibitors and
      differential expression patterns of hormonal receptors. A PubMed-database search
      was conducted to include all entries published with the keywords "BREAST CANCER
      NSAID ANTI-INFLAMMATORY" until 10/24/2013 providing original results from cohort
      studies, case-control studies, or randomized clinical trials with at least one
      reported relative risk (RR) or odds ratio (OR) on the association between any
      NSAID use and incidence of invasive breast cancer. This resulted in 49
      publications, from which the information was retrieved about type of study,
      exposure characteristics, breast cancer characteristics, and breast cancer-NSAID
      association. Meta-analyses were performed separately for case-control and cohort
      studies and for different hormone-receptor status. NSAID use reduced invasive
      breast cancer risk by about 20 %. A similar effect was found for aspirin,
      acetaminophen, COX-2 inhibitors and, to a lesser extent, ibuprofen. The effect of
      aspirin was similar in preventing hormone-receptor-positive breast cancer. This
      meta-analysis suggests a slightly protective effect of NSAIDs-especially aspirin
      and COX-2 inhibitors- against breast cancer, which seems to be restricted to
      ER/PR+tumors.

PMID- 25589175
TI  - Erratum: CT signs, patterns and differential diagnosis of solitary fibrous tumors
      of the pleura: Erratum.
AB  - [This corrects the article on p. 21 in vol. 2, PMID: 22263012.]. 

PMID- 25589173
TI  - Engineering synthetic antibody binders for allosteric inhibition of prolactin
      receptor signaling.
AB  - BACKGROUND: Many receptors function by binding to multiple ligands, each
      eliciting a distinct biological output. The extracellular domain of the human
      prolactin receptor (hPRL-R) uses an identical epitope to bind to both prolactin
      (hPRL) and growth hormone (hGH), yet little is known about how each hormone
      binding event triggers the appropriate response. FINDINGS: Here, we utilized a
      phage display library to generate synthetic antibodies (sABs) that preferentially
      modulate hPRL-R function in a hormone-dependent fashion. We determined the
      crystal structure of a sAB-hPRL-R complex, which revealed a novel allosteric
      mechanism of antagonism, whereby the sAB traps the receptor in a conformation
      more suitable for hGH binding than hPRL. This was validated by examining the
      effect of the sABs on hormone internalization via the hPRL-R and its downstream
      signaling pathway. CONCLUSIONS: The findings suggest that subtle structural
      changes in the extracellular domain of hPRL-R induced by each hormone determine
      the biological output triggered by hormone binding. We conclude that sABs
      generated by phage display selection can detect these subtle structural
      differences, and therefore can be used to dissect the structural basis of
      receptor-ligand specificity.

PMID- 25589174
TI  - Synanthropic rodents and their ectoparasites as carriers of a novel haemoplasma
      and vector-borne, zoonotic pathogens indoors.
AB  - BACKGROUND: Despite their close association with human dwellings, the role of
      synanthropic rodents in the epidemiology of vector-borne infections is seldom
      studied. The aim of the present study was to compensate for this lack of
      information, by the molecular investigation of vector-borne bacteria in
      peridomestic rodents and their ectoparasites. FINDINGS: Fifty-two rodents (mainly
      house mice and brown rats) were caught alive in buildings and checked for blood
      sucking ectoparasites; followed by molecular analysis of these, together with
      spleen samples, for the presence of vector-borne agents. Haemoplasma infection
      was significantly more prevalent among brown rats, than among house mice. A novel
      haemoplasma genotype (with only 92-93% similarity to Candidatus Mycoplasma
      turicensis and M. coccoides in its 16S rRNA gene) was detected in a harvest mouse
      and a brown rat. Sporadic occurrence of Rickettsia helvetica, Anaplasma
      phagocytophilum, Borrelia burgdorferi s.l. and Bartonella sp. was also noted in
      rodents and/or their ectoparasites. CONCLUSIONS: These results indicate that
      synanthropic rodents, although with low prevalence, may carry zoonotic and vector
      borne pathogens indoors.

PMID- 25589176
TI  - [Results of surgical treatment of patients with internal carotid artery kinking
      depending on methods of its reconstruction].
AB  - It was analyzed the results of surgical treatment of 60 patients with internal
      carotid artery kinking operated in the department of vascular surgery of acad.
      B.V. Petrovsky Russian Scientific Center of Surgery of RAN. Indications for
      surgery included symptoms of cerebrovascular insufficiency (CVI) and
      instrumentally confirmed hemodynamically significant kinking of ICA. Criteria for
      surgical treatment were linear flow velocity gradient more than 2 and turbulent
      blood flow in the kinking segment diagnosed by ultrasonic scanning. All patients
      were divided into 2 groups depending on methods of surgery. The first group
      included 36 (60%) patients who underwent resection of ICA with orifice bringing
      down. The second group included 8 (13%) patients after ICA replacement and 16
      (27%) cases with eversion endarterectomy, resection of ICA and orifice bringing
      down. The analysis of immediate surgery results did not reveal significant
      differences in dynamics of CVI and velocity parameters in reconstructed ICA
      (p>0.05). The index "stroke+mortality from stroke" was higher in the second group
      (p<0.05). Thrombosis of ICA reconstruction area has been developing more frequent
      (p<0.05) after ICA replacement (8%) in comparison with resection of ICA with
      orifice bringing down (0) and eversion endarterectomy, resection of ICA and
      orifice bringing down (0). Our data show that resection of ICA with orifice
      bringing down is preferable for surgical treatment of ICA kinking. ICA
      replacement is associated with significantly more frequent complications.
      Eversion endarterectomy with resection of ICA is optimal in case of combination
      of kinking with stenosis of ICA. 

PMID- 25589177
TI  - [Permanent vascular accesses in patients with chronic renal failure undergoing
      hemodialysis].
AB  - The article presents an experience of arteriovenous fistulas forming and using in
      78 patients with end-stage chronic renal failure undergoing hemodialysis. New
      methods for permanent vascular accesses forming were suggested. These techniques
      increased the operation period of arteriovenous fistulas. 

PMID- 25589178
TI  - [Opportunities for volatile fatty acids using in early diagnostics of infected
      pancreonecrosis].
AB  - It was analyzed the treatment results of 108 patients with pancreonecrosis (PN).
      Gas-liquid chromatography with definition of blood concentration of volatile
      fatty acids (VFA) was used additionally for timely diagnostics of infected
      pancreonecrosis. Volatile fatty acids are toxic metabolites of microorganisms.
      Statistically significant threshold values of VFA were revealed. These values
      allow to diagnose timely early phase of PN infection and the nature of the
      microflora. It was defined changes of VFA depending on the severity of infectious
      process in pancreas and retroperitoneal fiber. 

PMID- 25589179
TI  - [Experience of surgical treatment of abdominal and intraabdominal desmoid
      fibromas].
AB  - It is presented the treatment results of abdominal and intraabdominal desmoid
      fibromas. Group of abdominal localization included 19 patients. 15 of them had
      primary tumors, 4 - recurrent tumors after surgical treatment. Radical (R0)
      operations were performed in all cases. Tumor removal was associated with plastic
      of abdominal wall by synthetic implant in 17 patients. Wide excision of
      surrounding tissues and musculo-aponeurotic layer of anterior abdominal wall
      allows to achieve long-term disease-free period. There weren't recurrent symptoms
      in terms from 4 to 60 months of observation. The second group included 28
      patients with intraabdominal desmoid fibromas. Operations were performed in 11
      (35.2%) patients including 3 cases of reoperations. There were 14 operations.
      Radical (R0) volume was applied in 11 (78.6%) operations, cytoreductive (R2)
      volume - in 1 (7%) operation. Explorative laparotomy was used in 3 (21.4%) cases
      because of involvement of mesenteric vessels. Combined treatment was performed in
      4 (14.3%) patients. 14 (50%) patients received conservative therapy because of
      unresectable tumor including chemo-, hormone- and radiotherapy. Operated patients
      were under observation in terms from 11 to 156 months, median was 63.2 months.
      Recurrence developed in 4 of 10 (40%) patients after R0-surgery. Cytoreductive
      (R1/R2) volume is admitted for intraabdominal desmoid fibromas. But even in case
      of unresectable process and explorative intervention stabilization and regression
      of tumor is possible by means of chemo-, hormone- and radiotherapy in different
      combination. It allows to preserve a good life quality. 

PMID- 25589180
TI  - [Early complications after surgery for middle- and lower-ampullar cancer: total
      mesorectumectomy or "blind" preparation of rectum?].
AB  - It was performed a comparative analysis of parameters of early postoperative
      period in 318 patients with middle- and lower-ampullar cancer of rectum who
      underwent total mesorectumectomy and "blind" preparation of rectum. All patients
      were divided into 2 groups. The main group included 202 patients after total
      mesorectumectomy. The control group included 116 patients after "blind"
      preparation of rectum. Statistically significant differences in frequency of
      laparotomy wounds suppuration, urinary tract dysfunction and postoperative
      mortality were revealed. These complications were diagnosed more frequent in case
      of "blind" preparation of rectum. In the main group laparotomy wounds suppuration
      depended on sex (p<0.001, r=0.65), in the control group - on surgeon's experience
      (p=0.006, r=0.58), localization of tumor (p<0.001, r= -0.87) and type of surgery
      (p<0.001, r= -0.76). Urinary tract dysfunction after total mesorectumectomy
      depended on patient's sex (p<0.001, r=-0.77), after "blind" preparation of rectum
      - sex (p=0.002, r= -0.39) and performing of preoperative radiation therapy
      (p<0.001, r=0.46). In the main group none of the analyzed variables effected on
      the postoperative mortality. In the control group age (p=0.006, r=0.48),
      intraoperative blood loss (p=0.002, r=0.55), anastomosis failure (p=0.01,
      r=0.61), postoperative bleeding (p<0.001, r=0.88), early adhesive intestinal
      obstruction (p=0.006, r=0.77) effected on the mortality. It is considered that
      total mesorectumectomy in comparison with "blind" preparation of rectum decreases
      frequency of postoperative complications and mortality. 

PMID- 25589181
TI  - [The criteria for choose of treatment method of children with spleen injuries].
AB  - It was performed cohort prospective study of treatment results of 69 children
      with through-capsule spleen injuries for the period from 2002 to 2013. Patients
      were divided into 2 groups. The first group included 63 patients after non
      surgical treatment. The second group included 6 children who underwent surgery.
      In the first group 95.3% of patients had stable hemodynamics at admission. In the
      second group only 2 patients had the signs of deferred bleeding. Continuing
      abdominal bleeding was the indication for surgery in 4 patients although stable
      hemodynamics. Hemoperitoneum in case of spleen injury is not significant
      prognostic factor defining the tactics of treatment. The physiological response
      on bleeding but not the amount of blood in abdominal cavity determines tactics of
      treatment. Hemodynamic status is single statistically significant criterion for
      choose of surgical treatment of children with spleen injuries. Unstable
      hemodynamics increases the risk of surgical treatment in 20 times (p<0.007). 

PMID- 25589182
TI  - [Comparative results of surgical treatment of patients with morbid obesity].
AB  - It was performed a comparative analysis of treatment of 62 patients who were
      operated for morbid obesity. Patients were divided into 3 groups depending on
      kind of surgery: jejunal-iliac intestinal bypass, restrictive operations and
      combined operations. The complications in early postoperative period were
      diagnosed in 16.6% of patients after jejunal-iliac intestinal bypass and in 10%
      of patients after combined operations. Regardless of the kind of surgery there
      was rapid reduction of the body mass in the first year of observation with
      gradual increase of weight by an average of 5% in the subsequent period. The
      highest rate of weight loss by the second year was revealed after combined
      operations (up to 73.4%). Thus it was 1.1 times more than after jejunal-iliac
      intestinal bypass and 1.3 times more than after restrictive operations. 

PMID- 25589183
TI  - [Effect of hepatic functional activity of the liver and endogenous intoxication
      in patients with ovarian cancer].
AB  - The analysis of the clinical observations and the results of the study 70
      patients with ovarian cancer stage III-IV, aged 30 to 70 years. After various
      programs chemotherapy underwent surgical treatment stage under general
      anesthesia. Investigated hematological indices of intoxication, protein-synthetic
      liver function, transaminase, C-reactive protein, hemostasis in the perioperative
      period. Analysis of the results revealed that the original premorbid background
      characterized by severe hepatic dysfunction, endogenous intoxication, activation
      of the systemic inflammatory response. The introduction of the treatment of
      patients with ovarian cancer Remaxol promotes more pronounced and rapid reduction
      in the degree of metabolic disorders, endogenous intoxication and systemic
      inflammatory response, compared with ademethionine. 

PMID- 25589184
TI  - [Aspects of the practical application of direct oral anticoagulants in
      traumatological and orthopedic hospital].

PMID- 25589185
TI  - [Current concept of peptic ulcer disease: an endoscopist's view].

PMID- 25589186
TI  - [Thoracoscopic lobectomy for giant pulmonary arterio-venous aneuryzm].

PMID- 25589187
TI  - [Laparoscopic combined resection of sigmoid colon, panhysterectomy with removal
      through vagina stump].

PMID- 25589188
TI  - [Perfused bone autograft from medial epicondyle of femur in treatment of false
      joint of navicular bone].

PMID- 25589189
TI  - [Surgical treatment of patient with echinococcus cyst of left ventricle apex].

PMID- 25589190
TI  - LUX-Lung: determining the best EGFR inhibitor in NSCLC?

PMID- 25589192
TI  - Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for
      patients with rectal cancer: a systematic review and meta-analysis of individual
      patient data.
AB  - BACKGROUND: The role of adjuvant chemotherapy for patients with rectal cancer
      after preoperative (chemo)radiotherapy and surgery is uncertain. We did a meta
      analysis of individual patient data to compare adjuvant chemotherapy with
      observation for patients with rectal cancer. METHODS: We searched PubMed,
      Medline, Embase, Web of Science, the Cochrane Library, CENTRAL, and conference
      abstracts to identify European randomised, controlled, phase 3 trials comparing
      observation with adjuvant chemotherapy after preoperative (chemo)radiotherapy and
      surgery for patients with non-metastatic rectal cancer. The primary endpoint of
      interest was overall survival. FINDINGS: We analysed data from four eligible
      trials, including data from 1196 patients with (y)pTNM stage II or III disease,
      who had an R0 resection, had a low anterior resection or an abdominoperineal
      resection, and had a tumour located within 15 cm of the anal verge. We found no
      significant differences in overall survival between patients who received
      adjuvant chemotherapy and those who underwent observation (hazard ratio [HR]
      0.97, 95% CI 0.81-1.17; p=0.775); there were no significant differences in
      overall survival in subgroup analyses. Overall, adjuvant chemotherapy did not
      significantly improve disease-free survival (HR 0.91, 95% CI 0.77-1.07; p=0.230)
      or distant recurrences (0.94, 0.78-1.14; p=0.523) compared with observation.
      However, in subgroup analyses, patients with a tumour 10-15 cm from the anal
      verge had improved disease-free survival (0.59, 0.40-0.85; p=0.005,
      p(interaction)=0.107) and fewer distant recurrences (0.61, 0.40-0.94; p=0.025,
      p(interaction)=0.126) when treated with adjuvant chemotherapy compared with
      patients undergoing observation. INTERPRETATION: Overall, adjuvant fluorouracil
      based chemotherapy did not improve overall survival, disease-free survival, or
      distant recurrences. However, adjuvant chemotherapy might benefit patients with a
      tumour 10-15 cm from the anal verge in terms of disease-free survival and distant
      recurrence. Further studies of preoperative and postoperative treatment for this
      subgroup of patients are warranted. FUNDING: None.

PMID- 25589191
TI  - Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung
      adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data
      from two randomised, phase 3 trials.
AB  - BACKGROUND: We aimed to assess the effect of afatinib on overall survival of
      patients with EGFR mutation-positive lung adenocarcinoma through an analysis of
      data from two open-label, randomised, phase 3 trials. METHODS: Previously
      untreated patients with EGFR mutation-positive stage IIIB or IV lung
      adenocarcinoma were enrolled in LUX-Lung 3 (n=345) and LUX-Lung 6 (n=364). These
      patients were randomly assigned in a 2:1 ratio to receive afatinib or
      chemotherapy (pemetrexed-cisplatin [LUX-Lung 3] or gemcitabine-cisplatin [LUX
      Lung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or
      other) and ethnic origin (LUX-Lung 3 only). We planned analyses of mature overall
      survival data in the intention-to-treat population after 209 (LUX-Lung 3) and 237
      (LUX-Lung 6) deaths. These ongoing studies are registered with
      ClinicalTrials.gov, numbers NCT00949650 and NCT01121393. FINDINGS: Median follow
      up in LUX-Lung 3 was 41 months (IQR 35-44); 213 (62%) of 345 patients had died.
      Median follow-up in LUX-Lung 6 was 33 months (IQR 31-37); 246 (68%) of 364
      patients had died. In LUX-Lung 3, median overall survival was 28.2 months (95% CI
      24.6-33.6) in the afatinib group and 28.2 months (20.7-33.2) in the pemetrexed
      cisplatin group (HR 0.88, 95% CI 0.66-1.17, p=0.39). In LUX-Lung 6, median
      overall survival was 23.1 months (95% CI 20.4-27.3) in the afatinib group and
      23.5 months (18.0-25.6) in the gemcitabine-cisplatin group (HR 0.93, 95% CI 0.72
      1.22, p=0.61). However, in preplanned analyses, overall survival was
      significantly longer for patients with del19-positive tumours in the afatinib
      group than in the chemotherapy group in both trials: in LUX-Lung 3, median
      overall survival was 33.3 months (95% CI 26.8-41.5) in the afatinib group versus
      21.1 months (16.3-30.7) in the chemotherapy group (HR 0.54, 95% CI 0.36-0.79,
      p=0.0015); in LUX-Lung 6, it was 31.4 months (95% CI 24.2-35.3) versus 18.4
      months (14.6-25.6), respectively (HR 0.64, 95% CI 0.44-0.94, p=0.023). By
      contrast, there were no significant differences by treatment group for patients
      with EGFR Leu858Arg-positive tumours in either trial: in LUX-Lung 3, median
      overall survival was 27.6 months (19.8-41.7) in the afatinib group versus 40.3
      months (24.3-not estimable) in the chemotherapy group (HR 1.30, 95% CI 0.80-2.11,
      p=0.29); in LUX-Lung 6, it was 19.6 months (95% CI 17.0-22.1) versus 24.3 months
      (19.0-27.0), respectively (HR 1.22, 95% CI 0.81-1.83, p=0.34). In both trials,
      the most common afatinib-related grade 3-4 adverse events were rash or acne (37
      [16%] of 229 patients in LUX-Lung 3 and 35 [15%] of 239 patients in LUX-Lung 6),
      diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUX-Lung 3 only), and
      stomatitis or mucositis (13 [5%] in LUX-Lung 6 only). In LUX-Lung 3, neutropenia
      (20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were
      the most common chemotherapy-related grade 3-4 adverse events, while in LUX-Lung
      6, the most common chemotherapy-related grade 3-4 adverse events were neutropenia
      (30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]).
      INTERPRETATION: Although afatinib did not improve overall survival in the whole
      population of either trial, overall survival was improved with the drug for
      patients with del19 EGFR mutations. The absence of an effect in patients with
      Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be
      distinct from Leu858Arg-positive disease and that these subgroups should be
      analysed separately in future trials. FUNDING: Boehringer Ingelheim.

PMID- 25589193
TI  - Hemophagocytic lymphohistiocytosis syndrome in dengue hemorrhagic Fever: authors'
      reply.

PMID- 25589194
TI  - Hemophagocytic lymphohistiocytosis syndrome in dengue hemorrhagic Fever:
      correspondence.

PMID- 25589195
TI  - Outcome of Rhino-Sinus Mucormycosis in Children with Type 1 Diabetes.

PMID- 25589196
TI  - On Some Practical Considerations Regarding Community-Based Participatory Research
      for Addressing Cancer Health Disparities.
AB  - There is a consensus about the benefits of community-based participatory research
      and the important role it can play in reducing cancer health disparities.
      Although every community-based participatory research project is unique in many
      ways, several fundamental issues deserve consideration. We discuss issues
      concerning community representation, possible tensions within community-based
      participatory research (CBPR) projects, and staffing CBPR projects. Flexibility,
      open-mindedness, transparency, and above all, caring, are characteristics that
      best ensure successful and rewarding outcomes. 

PMID- 25589197
TI  - Heart Rate Turbulence and T-Wave Alternans in Patients with Coronary Artery
      Disease: The Influence of Diabetes.
AB  - BACKGROUND: Patients with diabetes mellitus (DM) have a higher risk of sudden
      cardiac death. Factors associated with the risk profiles of coronary artery
      disease (CAD) patients with DM are not well established. Heart rate turbulence
      (HRT) and T-wave alternans (TWA) are often used to predict arrhythmia events.
      METHODS AND RESULTS: HRT and TWA were measured in two independent groups: the
      ARTEMIS cohort study and the REFINE-ICD randomized trial. ARTEMIS assesses risk 3
      12 months after coronary angiography in patients with CAD. The initial 1001
      patients in ARTEMIS, 526 with and 475 without DM, are included in this analysis.
      REFINE-ICD compares usual care versus usual care plus ICD therapy in patients
      with left ventricular (LV) ejection fraction (EF) values of 36-50% assessed 2-15
      months after myocardial infarction. The initial 275 patients screened in REFINE
      ICD are included in this analysis. Abnormal HRT plus TWA was more common in
      patients with versus without DM in ARTEMIS (125/526, 24% vs 63/475, 13%; P <
      0.001) and REFINE-ICD (43/55, 78% vs 55/220, 25%; P < 0.001), respectively.
      Abnormal HRT plus TWA was also more common in patients with LVEF values < 50%
      (28%) vs >= 50% (18%; P < 0.001) in ARTEMIS and LVEF values below the population
      median of 42% (60/138, 43%) versus above the median (38/137, 28%; P < 0.01) in
      REFINE-ICD. CONCLUSIONS: Abnormal HRT plus TWA is more common in CAD patients
      with DM compared with the patients without DM and is related to the severity of
      LV dysfunction. CLINICAL TRIAL REGISTRATION INFORMATION:
      http://www.clinicaltrials.gov, NCT01426685; http://www.clinicaltrials.gov,
      NCT00673842.

PMID- 25589199
TI  - Effective combination of LED-based visible light, photosensitizer and
      photocatalyst to combat Gram (-) bacteria.
AB  - The aim of this study was to investigate antimicrobial efficiency of combined
      treatments of visible light (405nm), chlorophyllin (Chl) and ZnO nanoparticles
      (NPs). Results obtained indicate that incubation of the Gram (-) Escherichia coli
      with Chl (1.5*10(-5)M) for 60min as well as illumination alone (405nm;
      380kJ/m(2)) has no impact on the viability of E. coli. Just photosensitization
      (60min incubation with 1.5*10(-5)M Chl and following illumination, 405nm;
      380kJ/m(2)) slightly reduces their population (~1.5 log). ZnO NPs (5*10(-4)M) in
      the dark have negligible effect on E. coli viability. However, photocatalytic
      treatment (10min incubation with ZnO NPs (5*10(-4)M) and following illumination
      with light (lambda=405nm; 380kJ/m(2)) resulted in significant reduction of viable
      cell population (4.6 log). Scanning electron microscopy (SEM) images indicate
      that cell surface-adhered NPs as well as chlorophyllin after illumination trigger
      cell shrinkage and eventually death. Simultaneous (at the same time) incubation
      30min. with Chl and ZnO NPs and following illumination (380kJ/m(2)) was less
      effective than every treatment separately. Interaction of bacteria with
      photosensitizer and photocatalyst in the sequence (photosensitizer->photocatalyst
      >light) reduced the viability of bacteria by 3 log. But applying interaction of
      bacteria with photosensitizer and photocatalyst in opposite order (photocatalyst
      >photosensitizer->light) looks more promising as this reduced the Gram (-) E.
      coli microbial population by 4.5 log using 5 times lower photocatalyst
      concentration in comparison with efficiency of photoactivated ZnO NPs (4.6 log).
      In this case ZnO NPs interact electrostatically with negatively-charged cell
      surface and afterwards bind negatively charged Chl, thus act as mediators between
      negatively-charged cell surface and negatively-charged photosensitizer.

PMID- 25589200
TI  - Erratum to: Vedolizumab: A Review of Its Use in Adult Patients with Moderately to
      Severely Active Ulcerative Colitis or Crohn's Disease.

PMID- 25589198
TI  - Monitoring aspirin therapy in children after interventional cardiac
      catheterization: laboratory measures, dose response, and clinical outcomes.
AB  - Very few studies have investigated dose response of aspirin and agreement of
      different platelet function assays in children. One hundred five children were
      studied at baseline and after interventional cardiac catheterization during
      aspirin treatment and, in cases of aspirin resistance (AR), after dose increase.
      Results from arachidonate-induced aggregation (AA) were compared with aggregation
      induced by ADP, PFA-100 closure times (CTs), urinary 11-dehydro-thromboxane B2
      (urinary 11-dhTxB2) levels, and Impact-R % surface coverage. Aspirin at 2-5
      mg/kg/day inhibited platelet function in a large majority. While 19 % showed
      bruising and mild epistaxis, no thrombotic complications were recorded. AR was
      detected by AA in seven children (6.7 %). After dose increase, the majority
      showed inhibition by aspirin. Infants had higher urinary 11-dhTxB2 baseline
      levels; this assay showed some correlation with AA. Both assays manifested high
      sensitivity and specificity for aspirin while inferior results were found for the
      other assays. With the PFA-100, 15.2 % of patients were found to have AR, but
      this corresponded to AR by AA in only one of seven children. CONCLUSION: While
      there was poor agreement among assays, AA and urinary 11-dhTxB2 show good
      specificity for the monitoring of aspirin therapy in children. Aspirin at 2-5
      mg/kg inhibits platelet function; AR in children is rare and can be overcome by
      dose increase.

PMID- 25589201
TI  - Apatite-forming PEEK with TiO2 surface layer coating.
AB  - Polyetheretherketone (PEEK) is widely used in orthopedic implants, such as spinal
      fusion devices, because of its moderate elastic modulus, as well as relatively
      high mechanical strength. However, it does not bond to living bone, and hence it
      needs autograft to be fixed to the bone. In this study, we attempted to add bone
      bonding properties to PEEK by coating with TiO2 synthesized by the sol-gel
      process. When a TiO2 sol solution consisting of titanium isopropoxide, water,
      ethanol, and nitric acid was deposited on a PEEK substrate without any
      pretreatment, the formed TiO2 gel layer was easily peeled off after subsequent
      treatments. However, when the same solution was deposited on PEEK that was
      preliminarily subjected to UV or O2 plasma treatment, the deposited TiO2 gel
      layer strongly adhered to the substrate even after subsequent treatments. The
      strong adhesion was attributed to the interaction among the C-O, C=O, and O-C=O
      groups on the PEEK owing to the UV or O2 plasma treatment and the Ti-O bond of
      the TiO2 gel. Apatite did not form on the as-formed TiO2 gel layer in a simulated
      body fluid (SBF) even within 3 days; however, apatite formed after soaking in 0.1
      M HCl solution at 80  degrees C for 24 h. This apatite formation was attributed
      to positive surface charge of the TiO2 gel layer induced by the acid treatment.
      The PEEK with the TiO2 gel layer coating formed by the proposed process is
      expected to bond to living bone, because a positively charged titanium oxide
      which facilitates the formation of apatite in SBF within a short period is known
      to bond to living bone.

PMID- 25589202
TI  - Elasticity and structure of the compounds in the wollastonite (CaSiO3)-Na 2SiO 3
      system: from amorphous to crystalline state.
AB  - The elastic properties and structure of four potential bioactive compounds in the
      CaSiO3-Na2SiO3 system were characterized by Raman and Brillouin spectroscopy at
      ambient conditions. The increase of Na2O content in the Na2O-CaO-SiO2 glass with
      the same silica content and hence polymerization was found to lower the elastic
      moduli with accompanied decrease of Q(0) and Q(2) species, increase of Q(1)
      species and negligible change of Q(3) species, corresponding to a lower and
      higher equilibrium constant for the disproportional reactions [Formula: see text]
      and [Formula: see text] (without balance), respectively. The composition
      dependent variation in the shear modulus (G) of the Na2O-CaO-SiO2 glass can be
      attributed to the concentration change of Q(2) and probably Q(4) species; while
      bulk modulus (K) ascribed to the cohesion factor. The elastic moduli of the
      corresponding crystalline phases in this system also lower with the increase of
      Na2O content following two general criteria as a function of Na2O/CaO molar
      ratio: (1) K decreases faster than G for both the amorphous and crystalline
      phases and (2) both K and G decreases faster for the crystals than the glasses. 

PMID- 25589203
TI  - Experimental self-etching HEMA-free adhesive systems: cytotoxicity and degree of
      conversion.
AB  - The aim of this study was to evaluate the effect of replacing 2-hydroxyethyl
      methacrylate (HEMA) by methacrylate surfactant monomers on the cytotoxicity and
      degree of conversion of two-step self-etching dentin adhesive systems. Five HEMA
      free adhesive systems were tested: Bis-EMA 10, Bis-EMA 30, PEG400, PEG400UDMA,
      PEG1000, and a HEMA group was used as positive control. The cytotoxicity of the
      experimental primers, with different monomer concentrations (2 or 20 wt%), and
      bond resins, containing 25 wt% surfactant, was assessed using murine fibroblast
      cell line 3T3 and the tetrazolium assay (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT)). The degree of conversion of the bond resins
      was analyzed using Fourier transform infrared spectroscopy. The data were
      submitted to statistical analysis using level of significance set at P < 0.05.
      The PEG 1000 group obtained higher cell viability in comparison with HEMA in the
      2 % primer. The cell survival rate using 20 % primer showed that PEG1000 and BIS
      EMA 10 were less cytotoxic than HEMA. With regard to the eluate from bond resin,
      the data showed that the groups BIS-EMA 10, BIS-EMA 30 and PEG400UDMA were less
      cytotoxic than HEMA. No statistically significant difference was found among
      degrees of conversion of the experimental groups and HEMA. PEG 1000, BIS-EMA 10
      and 30 monomers showed the biological potential for use in new adhesive system
      formulations since they showed lower cytotoxicity and similar degree of
      conversion when compared with the HEMA-containing group. 

PMID- 25589204
TI  - New TiAg composite coating for bone prosthesis engineering shows promising
      microvascular compatibility in the murine dorsal skinfold chamber model.
AB  - The incorporation of antimicrobial substances like silver into implant surface
      coatings is one promising concept against primary infections of endoprosthesis,
      especially for immunocompromised patients as well as against reinfection after
      revision operations. However, besides good antimicrobial and mechanical
      properties it is equally important that the implant material does not disturb the
      local microvascular perfusion of muscle tissue to enable microbial host defense
      and tissue repair processes. In this study the biocompatibility of a newly
      developed TiAg-composite coating applied on conventional titanium via physical
      vapor deposition was analysed. To evaluate the local microvascular and
      inflammatory response of striated muscle tissue upon implantation of TiAg-coated
      plates the murine dorsal skinfold chamber model was used. We repetitively
      examined local capillary and venular perfusion, endothelial integrity as well as
      leucocyte activation by intravital fluorescence microscopy at 1 h, 24 h as well
      as 3 and 7 days after implantation. TiAg-implants were well tolerated by the
      vascular system as indicated by intact functional capillary density and
      endothelial integrity compared to pure titanium plates and controls without a
      metal implant. Furthermore, quantification of rolling and adherent leucocytes did
      not reveal signs of inflammation upon TiAg-implantation.

PMID- 25589205
TI  - Anticancer activity of fungal L-asparaginase conjugated with zinc oxide
      nanoparticles.
AB  - Demand for developing novel delivery system for cancer treatment has increased
      due to the side effects present in intravenous injection of L-asparaginase.
      Nanoparticles are used for delivering the drugs to its destination in cancer
      cure. Nanobiocomposite of zinc oxide nanoparticles conjugated with L-asparaginase
      was produced by Aspergillus terreus and was confirmed using maximum UV-Vis
      absorption at 340 nm in the present work. The presence of functional groups like
      OH, C-H, -C=N and C=O on the surface of nanobiocomposite was found from Fourier
      transform infrared spectrum analysis. Size of the produced nanocomposite was
      found in the range of 28-63 nm using scanning electron microscope. The
      crystalline nature of the synthesized nanobiocomposites was confirmed by X-ray
      diffraction analysis. The presence of zinc oxide on synthesized nanobiocomposite
      was confirmed by energy dispersive spectrum analysis. The anti-cancerous nature
      of the synthesized zinc oxide conjugated L-asparaginase nanobiocomposite on MCF-7
      cell line was studied using MTT assay. The viability of the MCF-7 cells was
      decreased to 35.02 % when it was treated with L-asparaginase conjugated zinc
      oxide nanobiocomposite. Hence it is proved that the synthesized nanobiocomposites
      of zinc oxide conjugated L-asparaginase has good anti-cancerous activity.

PMID- 25589206
TI  - Structure and properties of porous films based on aliphatic copolyamide developed
      for cellular technologies.
AB  - The effect of concentration and viscosity of the copolyamide (copolymer of
      epsilon-caprolactam and hexamethylendiaminadipate) solutions in aqueous/alcoholic
      solvents on its phase state was studied. The films obtained by the coagulation
      method were characterized by monodisperse pore distribution with an average pore
      size of 1.3 MUm. The films processed by electrospinning from copolyamide
      solutions were characterized by a bimodal distribution of macropores with one
      peak of pore radius at 2.0 MUm and second peak of pore radius at 20 MUm. The
      adhesion and proliferation of mesenchymal adhesion stem cells (ASCs) stem cells
      to copolyamide matrix were studied. With the help of scanning electron microscopy
      it was shown that both tapes porous films were characterized by good adhesion of
      mesenchymal ASCs stem cells. It was shown that the porous structure, transport
      and mechanical properties of these copolyamide films allow their use as two
      dimensional matrices for cellular technology.

PMID- 25589207
TI  - Effects of cathode design parameters on in vitro antimicrobial efficacy of
      electrically-activated silver-based iontophoretic system.
AB  - Post-operative infection is a major risk associated with implantable devices.
      Prior studies have demonstrated the effectiveness of ionic silver as an
      alternative to antibiotic-based infection prophylaxis and treatment. The focus of
      this study is on an electrically activated implant system engineered for active
      release of antimicrobial silver ions. The objective was to evaluate the effects
      of the cathode design, especially the cathode material, on the in vitro
      antimicrobial efficacy of the system. A modified Kirby-Bauer diffusion technique
      was used for the antimicrobial efficacy evaluations (24 h testing interval). In
      phase-1 of the study, a three-way ANOVA (n = 6, alpha = 0.05) was performed to
      determine the effects of cathode material (silver, titanium, and stainless
      steel), cathode surface area and electrode separation distance on the efficacy of
      the system against Staphylococcus aureus. The results show that within the design
      space tested, none of these parameters had a statistically significant effect on
      the antimicrobiality of the system (P > 0.15). Subsequently, one-way ANOVA (n =
      6, alpha = 0.05) was conducted in phase-2 to validate the inference regarding the
      non-significance of the cathode material to the system efficacy using a broader
      spectrum of pathogens (methicillin-resistant S. aureus, Escherichia coli,
      Streptococcus agalactiae and Aspergillus flavus) responsible for osteomyelitis.
      The results confirmed the lack of statistical difference between efficacies of
      the three cathode material configurations against all pathogens tested (P >
      0.58). Overall, the results demonstrate the ability to alter the cathode material
      and related design parameters in order to minimize the silver usage in the system
      without adversely affecting its antimicrobial efficacy.

PMID- 25589210
TI  - Electrochemical preparation of nanostructured lanthanum using lanthanum chloride
      as a precursor in 1-butyl-3-methylimidazolium dicyanamide ionic liquid.
AB  - Nanostructured lanthanum was electrochemically prepared on a platinum (Pt)
      substrate in the room temperature ionic liquid 1-butyl-3-methylimidazolium
      dicyanamide (BMI-DCA) containing anhydrous LaCl3 at 333 K. The electrochemical
      reduction behavior of La(iii) was investigated using cyclic voltammetry and
      chronoamperometry techniques. Cyclic voltammogram revealed that the reduction of
      La(iii) in BMI-DCA involved an irreversible process controlled by diffusion.
      Chronoamperometric transient analysis confirmed the diffusion controlled
      electrodeposition process with the diffusion coefficient of La(iii) species in
      the range of 10(-10) cm(2) s(-1). The strong complexing capability of DCA(-)
      anions facilitated the displacement of chloride ligands and induced the
      solubility of LaCl3. The subsequent coordination of La(iii) and DCA(-) anions
      forming [La(DCA)4](-) complex anions was monitored by designing amperometric
      titration experiments. Potentiostatically deposited La-deposits with different
      nanostructures were characterized by SEM, XRD and XPS analyses. The
      electrodeposition potential was found to play an important role in controlling
      the nucleation and growth kinetics of the nanocrystal during the
      electrodeposition process. Depending on the deposition potential, metallic
      lanthanum with either nanoparticles or nanoporous structures was obtained. 

PMID- 25589208
TI  - In vitro assessment of the soft tissue/implant interface using porcine gingival
      explants.
AB  - The biologic seal of peri-implant soft tissue is crucial for long-term prognosis
      of oral implants. This in vitro study describes a novel tissue culture model
      using porcine gingival explants to evaluate the soft tissue/implant interface.
      Two different types of substrates were investigated: (a) plain polymer: BisGMA
      TEGDMA (50-50 %) and (b) unidirectional fiber-reinforced composite (FRC). Porcine
      gingival explants were obtained from a local slaughterhouse. The experimental
      implants (n = 4) were inserted into the middle of freshly excised porcine
      gingival explants and cultured at the air/liquid interface up to 14 days. Porcine
      gingival explants with no implants served as baseline controls. The specimens
      were fixed and processed for the preparation of undecalcified samples.
      Histological analysis of the soft tissue/implant interface was carried out using
      a light-microscope. Microscopic evaluation suggests that the gingival explants
      established epithelial and connective tissue attachment to both implant types
      over the incubation period. FRC surfaces seemed to have a favorable tissue
      response with a sign of an outward epithelial migration. However, tissue
      degeneration was observed at the end of the experiment. In conclusion, this in
      vitro model maintains mucosal viability and ability to histologically evaluate
      soft tissue attachment to biomaterials rendering it a time efficient and cost
      effective model that may reduce the need for animal experiments.

PMID- 25589209
TI  - In situ synthesis of hydroxyapatite nanocomposites using iron oxide nanofluids at
      ambient conditions.
AB  - This paper describes a simple method for the room temperature synthesis of
      magnetite/hydroxyapatite composite nanocomposites using ferrofluids. The in situ
      synthesis of magnetic-hydroxyapatite results in a homogenous distribution of the
      two phases as seen both in transmission electron micrographs and assembled to a
      micron range in the confocal micrographs. The selected area diffraction pattern
      analysis shows the presence of both phases of iron oxide and hydroxyapatite. To
      the dialyzed ferrofluid, the constituents of hydroxyapatite synthesis was added,
      the presence of the superparamagnetic iron oxide particles imparts directionality
      to the hydroxyapatite crystal growth. Electron probe microanalysis confirms the
      co-existence of both iron and calcium atoms. Vibrating Sample magnetometer data
      shows magnetization three times more than the parent ferrofluid, the local
      concentration of iron oxide nanoparticles affects the strength of dipolar
      interparticle interactions changing the energy barrier for determining the
      collective magnetic behavior of the sample. The limitations inherent to the use
      of external magnetic fields which can be circumvented by the introduction of
      internal magnets located in the proximity of the target by a minimal surgery or
      by using a superparamagnetic scaffold under the influence of externally applied
      magnetic field inspires us to increase the magnetization of our samples. The
      composite in addition shows anti-bacterial properties against the two gram (-ve)
      bacteria tested. This work is significant as magnetite-hydroxyapatite composites
      are attracting a lot of attention as adsorbents, catalysts, hyperthermia agents
      and even as regenerative medicine. 

PMID- 25589211
TI  - Calcium intake and hypertension among obese adults in United States: associations
      and implications explored.
AB  - The relationship between calcium intake and hypertension is receiving increased
      research attention. The prevalence of hypertension is high among the obese
      populations. Calcium is a mineral that influences blood pressure. The aim of the
      study was to examine the association between calcium intake and hypertension in a
      large nationally representative sample of obese American adults. A total of
      14,408 obese adults aged 20 years or older were obtained from the 1999-2010
      National Health and Nutrition Examination Survey. Analysis of variance and linear
      regression models were used to examine relationships between calcium intake and
      systolic blood pressure (SBP) as well as diastolic blood pressure (DBP). Multiple
      logistic regression models were used to examine the association between calcium
      intake and hypertension after adjusting for potential confounders and
      interactions, including: age, race, education level, alcohol use, smoking,
      diabetes status, sodium intake and potassium intake. Calcium intake was
      significantly lower for the hypertensive group compared with the normotensive
      group (P<0.0001), especially among those obese female young adults aged 20-44
      years and among non-diabetic obese adults. Based on ordinary linear regression
      analysis, a significant inverse relationship was detected, SBP and DBP decreased
      if calcium intake increased (SBP: regression coefficient estimate=-0.015,
      P<0.0001; DBP: regression coefficient estimate=-0.028, P<0.0001). Multiple
      logistic regression showed that calcium intake was negatively associated with the
      probability of hypertension (odds ratio (OR)=0.81, 95% confidence interval (CI):
      0.74-0.87, P<0.0001). In stratified analysis, calcium intake in youngest adults
      (age 20-44 years) had the lowest likelihood of hypertension (OR=0.77, 95% CI:
      0.64-0.93, P<0.0001), the inverse relationship between calcium intake and
      probability of hypertension was stronger among females (OR: 0.68, 95% CI: 0.55
      0.84, P<0.0001), when compared with the whole sample including all of 14,408
      obese adults. The protective effect of calcium intake and hypertension was found
      significantly in obese non-diabetic adults (OR: OR=0.77, 95% CI: 0.67-0.89,
      P<0.0001) not in obese diabetic adults. SBP, DBP and calcium intake were log
      transformed for both ordinary linear regression analysis and logistic regression
      analysis. Our study findings underscore the need to explore the physiological
      mechanism between calcium intake and hypertension. In this study, increased
      calcium intake was associated with the lowest risk of hypertension. Future
      studies utilizing longitudinal research designs are needed to quantify
      therapeutic levels of calcium for control of hypertension among obese adults.
      Increasing calcium intake among American adults may offer promise as a cost
      effective strategy to improve hypertension among obese adults; however, further
      scientific exploration is warranted.

PMID- 25589212
TI  - Hypertension prevalence, awareness, treatment and control among Han and four
      ethnic minorities (Uygur, Hui, Mongolian and Dai) in China.
AB  - In the previous study, hypertension prevalence, awareness, treatment and control
      for Han and others four ethnic minorities (Uygur, Hui, Mongolian and Dai) has not
      been clearly documented in China. Therefore we used the baseline data of
      Prospective Urban and Rural Epidemiology (PURE) for further detailed study.
      Adjusted rate were estimated and compared through logistic regression after
      adjustment of age, sex, location and education. Among the total of 7137
      participants (Han: 1626, ethnic minorities: 5511), hypertension prevalence,
      awareness, treatment and control were 2922(40.9%), 1199(41.0%), 873(29.9%) and
      147(5.0%), respectively. The most commonly used antihypertensive drugs are
      traditional compound drugs (6.2%) and calcium channel blockers (5.2%).
      Hypertension prevalence in ethnic minorities was significantly higher than in Han
      (42.4% vs 34.4%, P<0.0001), while control rate (1.6% vs 9.8%, P=0.0198) and
      treated control rate (8.0% vs 25.0%, P=0.0200) were lower. Compared with Han
      counterparts, Dai had a higher prevalence (50.8% vs 29.9%, P<0.0001). Uygur had a
      lower treatment rate (33.2% vs 20.6%, P=0.0110). Mongolian had a lower control
      (5.1% vs 16.1%, P=0.0046) and treated control rate (14.1% vs 50.3%, P=0.0013). In
      conclusions, our study showed ethnic minorities had higher hypertension
      prevalence, especially for Dai and lower control and treated control rate for
      Mongolian. Hence, we need more attention with respect to hypertension in ethnic
      minorities. 

PMID- 25589213
TI  - Weight reduction and aortic stiffness in obese children and adolescents: a 1-year
      follow-up study.
AB  - Little is known about the effect of weight reduction on aortic stiffness and
      especially so in the young. The present study investigates whether weight
      reduction influences aortic stiffness in obese children and adolescents. Carotid
      femoral pulse wave velocity (cfPWV) and augmentation index at heart rate 75
      (AIx@HR75) were measured in 72 obese patients aged 10-18 years at baseline and
      after 1-year of lifestyle intervention (follow-up). We found that although the
      degree of obesity decreased (Deltabody mass index z-score: -0.24+/-0.45,
      P<0.0001), cfPWV was higher at follow-up (DeltacfPWV: 0.27+/-0.47 m s(-1),
      P<0.0001), which was explained by the increase in age (beta=0.12 ms(-1)  per
      year, 95% confidence interval (CI) 0.07-0.17, P<0.0001) and partly by changes in
      mean arterial pressure and heart rate. Changes in cfPWV were not related to
      changes in obesity measures. No significant change was found in AIx@HR75
      (DeltaAIx@HR75: 2.10+/-9.73%, P=0.072), but changes in AIx@HR75 were related to
      changes in abdominal fat (Deltawaist/height ratio: beta=50.3, 95% CI 6.7-94.0,
      P=0.02) and changes in total body fat percent by dual energy X-ray absorptiometry
      scan (Deltatotal body fat (%): beta=0.7, 95% CI 0.1-1.3, P=0.02) when adjusted
      for gender and relevant baseline confounders. In conclusion, no clear effect of
      weight reduction was found on aortic stiffness, although changes in AIx@HR75 were
      associated with changes in both abdominal fat and total body fat percent. The
      higher cfPWV at follow-up was related to the older age. 

PMID- 25589214
TI  - Resistant hypertension: do all definitions describe the same patients?
AB  - Resistant hypertension (RH) is defined as blood pressure (BP) that remains ?140
      and/or 90 mm Hg despite therapy with ?3 full-dose antihypertensive drugs
      (classical definition=CD). A definition proposed subsequently (new definition=ND)
      includes patients requiring ?4 drugs irrespective of BP values. We aimed to
      evaluate whether both definitions characterize the same kind of patients.One
      hundred and twenty-four consecutively attended patients with RH were classified
      into two groups according to their BP control: 66 patients had non-controlled BP
      (all those who met the CD criteria plus a few patients who met the ND criteria);
      58 patients had controlled BP (all with RH according to the ND). Clinical,
      laboratory and office BP data were recorded. RH patients with non-controlled BP
      were more frequently diabetic (72% vs 49%), and had higher plasmatic glucose (149
      vs 130 mg dl(-1)), cholesterol (179 vs 164 mg dl(-1)), low-density lipoprotein
      (LDL)-cholesterol (107 vs 95 mg dl(-1)) and triglyceride (169 vs 137 mg dl(-1))
      levels; P<0.05 for all comparisons. In multivariate logistic regression analysis,
      the variables that independently associated with non-controlled BP were diabetes
      (P=0.001) and higher LDL-cholesterol (P=0.007).We conclude that, although both
      cohorts of patients are phenotypically quite similar, uncontrolled RH patients
      have higher prevalence of diabetes mellitus and higher LDL-cholesterol levels
      than controlled RH patients. 

PMID- 25589215
TI  - Production benefits from pre- and post-lambing anthelmintic treatment of ewes on
      commercial farms in the southern North Island of New Zealand.
AB  - AIMS: To measure the magnitude and variability in production responses to
      anthelmintic treatments administered to adult ewes around lambing. METHODS: Ewes
      carrying twin lambs, from sheep and beef farms (eight in Year 1 and six in Year
      2) in the Wairarapa region of New Zealand, were enrolled in 14 trials (part of an
      experiment carried out on one farm in one year). Experiment 1 compared ewes
      treated 2-4 weeks pre-lambing with a controlled release capsule (CRC) containing
      abamectin, albendazole, Se and Co, to ewes injected pre-lambing with a long
      acting Se plus vitamin B12 product, and to untreated ewes. Experiment 2 included
      these treatments, plus a CRC administered at pregnancy scanning. Experiment 3
      included the same treatments as Experiment 1, plus administration of a CRC
      containing albendazole, Se and Co, injectable moxidectin or oral derquantel plus
      abamectin, all administered pre-lambing, or oral derquantel plus abamectin
      administered 4-6 weeks after lambing. Variables compared were ewe liveweight at
      weaning and pre-mating, lamb liveweight at weaning, total weight of lamb weaned
      per ewe and ewe dag score at weaning. RESULTS: Ewes treated with a CRC pre
      lambing were heavier than untreated ewes (mean 3.2 kg) at weaning in 12/14
      trials, and pre-mating (mean 2.8 kg) in 9/14 trials (p<0.001). Compared with
      mineral-treated ewes the mean difference was 2.8 kg pre-lambing (9/14 trials) and
      1.7 kg pre-weaning (6/14 trials). Lambs reared by treated ewes were heavier (mean
      1.55 kg) at weaning in 6/14 trials (p<0.001), but there was no effect of CRC
      treatment on total weight of lambs weaned per ewe (p=0.507). Variation in weight
      of lamb weaned per ewe was largely explained by differences in lamb survival from
      birth to weaning (p<0.001), with no effect of CRC treatment (p>0.65). Treatment
      of ewes with a CRC at pregnancy scanning was neither better nor worse than a pre
      lambing treatment (p=0.065). There was no difference in the response from
      treatment with either of the two CRC or moxidectin. Treatment with short-acting
      oral anthelmintics resulted in no consistent benefit. CONCLUSIONS: Anthelmintic
      treatments administered to ewes around lambing resulted in variable responses
      between farms and years, which in some trials were negative for some variables,
      and some of the variability was due to the mineral component of the CRC. The
      widespread perception amongst farmers and veterinarians that anthelmintic
      treatment of ewes around lambing will always result in positive benefits is not
      supported.

PMID- 25589216
TI  - ASTRAL-R score predicts non-recanalisation after intravenous thrombolysis in
      acute ischaemic stroke.
AB  - Intravenous thrombolysis (IVT) as treatment in acute ischaemic strokes may be
      insufficient to achieve recanalisation in certain patients. Predicting
      probability of non-recanalisation after IVT may have the potential to influence
      patient selection to more aggressive management strategies. We aimed at deriving
      and internally validating a predictive score for post-thrombolytic non
      recanalisation, using clinical and radiological variables. In thrombolysis
      registries from four Swiss academic stroke centres (Lausanne, Bern, Basel and
      Geneva), patients were selected with large arterial occlusion on acute imaging
      and with repeated arterial assessment at 24 hours. Based on a logistic regression
      analysis, an integer-based score for each covariate of the fitted multivariate
      model was generated. Performance of integer-based predictive model was assessed
      by bootstrapping available data and cross validation (delete-d method). In 599
      thrombolysed strokes, five variables were identified as independent predictors of
      absence of recanalisation: Acute glucose > 7 mmol/l (A), significant extracranial
      vessel STenosis (ST), decreased Range of visual fields (R), large Arterial
      occlusion (A) and decreased Level of consciousness (L). All variables were
      weighted 1, except for (L) which obtained 2 points based on beta-coefficients on
      the logistic scale. ASTRAL-R scores 0, 3 and 6 corresponded to non-recanalisation
      probabilities of 18, 44 and 74 % respectively. Predictive ability showed AUC of
      0.66 (95 %CI, 0.61-0.70) when using bootstrap and 0.66 (0.63-0.68) when using
      delete-d cross validation. In conclusion, the 5-item ASTRAL-R score moderately
      predicts non-recanalisation at 24 hours in thrombolysed ischaemic strokes. If its
      performance can be confirmed by external validation and its clinical usefulness
      can be proven, the score may influence patient selection for more aggressive
      revascularisation strategies in routine clinical practice.

PMID- 25589217
TI  - Virulence-targeted Antibacterials: Concept, Promise, and Susceptibility to
      Resistance Mechanisms.
AB  - In view of the relentless increase in antibiotic resistance in human pathogens,
      efforts are needed to safeguard our future therapeutic options against infectious
      diseases. In addition to regulatory changes in our antibiotic use, this will have
      to include the development of new therapeutic compounds. One area that has
      received growing attention in recent years is the possibility to treat or prevent
      infections by targeting the virulence mechanisms that render bacteria pathogenic.
      Antivirulence targets include bacterial adherence, secretion of toxic effector
      molecules, bacterial persistence through biofilm formation, quorum sensing and
      immune evasion. Effective small-molecule compounds have already been identified
      that suppress such processes. In this review, we discuss the susceptibility of
      such compounds to the development of resistance, by comparison with known
      resistance mechanisms observed for classical bacteriostatic or bacteriolytic
      antibiotics, and by review of available experimental case studies. Unfortunately,
      appearance of resistance mechanisms has already been demonstrated for some,
      showing that the quest of new, lasting drugs remains complicated. 

PMID- 25589218
TI  - The modified quasi-quantum treatment of rotationally inelastic NO(X)-He
      scattering.
AB  - A modified quasi-quantum treatment (MQQT) of molecular scattering has been
      developed to account for the softness of the repulsive part of the anisotropic
      atom-molecule PES. A contour of the PES is chosen such that the barrier height is
      just large enough to reflect the incoming kinetic energy, directed anti-parallel
      to the hard shell normal at the site of impact. The resulting rotationally
      inelastic quantum state resolved DCSs and ICSs of He + NO(X) at Ecol = 508 cm(-1)
      are compared to those obtained from regular QQT and from quantum mechanically
      exact calculations performed on the full highest quality ab initio Vsum PES. The
      MQQT parity changing DCSs for Deltaj <= 4 exhibit much better agreement with the
      QM DCSs than is obtained using regular QQT, particularly in the forward scattered
      direction. The improvements upon the remaining MQQT DCSs with respect to the
      regular QQT were minor, due to the near incompressible hard shell character of
      the n ? 1 or 3 anisotropic Legendre polynomial terms of the PES. 

PMID- 25589219
TI  - Intermolecular enantioselective dearomatization reaction of beta-naphthol using
      meso-aziridine: a bifunctional in situ generated magnesium catalyst.
AB  - A direct, facile, and highly diastereo- and enantioselective dearomatization
      reaction of beta-naphthol derivatives with aziridines has been developed for the
      first time. A newly designed Box-OH ligand was employed for an in situ generated
      magnesium catalyst and proved to be efficient. The corresponding dearomatization
      product was transformed into a polycyclic scaffold and polyhydroxylated compound.
      (1) H NMR studies revealed the activation mode of the dearomatization process of
      beta-naphthols, and a clear positive nonlinear effect was observed in the
      reaction, and provides insight into the coordination environment around the
      Mg(II) center and the possible active species. 

PMID- 25589221
TI  - Erratum to: does saturable formation of gemcitabine triphosphate occur in
      patients?

PMID- 25589220
TI  - Effect of axitinib on the QT interval in healthy volunteers.
AB  - PURPOSE: Axitinib is a potent and selective inhibitor of vascular endothelial
      growth factor receptors 1-3, approved for second-line treatment of advanced renal
      cell carcinoma (RCC). Preclinical studies did not indicate potential for axitinib
      induced delayed cardiac repolarization. METHODS: The effect of axitinib on
      corrected QT (QTc) prolongation was evaluated with one-stage concentration-QTc
      response modeling using data from a definitive randomized crossover QT phase I
      study in healthy volunteers administered one single 5-mg axitinib dose alone or
      in the presence of steady-state ketoconazole (400 mg once daily). RESULTS:
      Axitinib and ketoconazole had opposite effects on heart rate: Axitinib lowered
      it, ketoconazole raised it. The final analysis showed a flat relationship between
      QTc and axitinib concentration (slope -0.0314 ms.mL/ng) for axitinib alone. Mean
      highest placebo-matched change from baseline in QTc was -3.0 [90 % confidence
      interval (CI) -5.4, -0.6] ms. At supratherapeutic axitinib exposures achieved
      with potent cytochrome P450 3A4/5 inhibition by ketoconazole, the model predicted
      mean QTc change of 6.5 (90 % CI 4.4-8.5) ms. The slope population mean estimate
      was -0.331 (95 % CI -0.860, 0.198) ms.mL/ug for ketoconazole alone and 0.0725
      (0.0445-0.1005) ms.mL/ng for axitinib in the presence of ketoconazole. The
      results were then compared with those obtained based on more widely used
      Fridericia's, Bazett's, and study-specific correction methods. CONCLUSIONS: Since
      axitinib plasma concentrations observed in this study exceeded the range of
      concentrations observed in patients with RCC at the highest approved clinical
      dose (10 mg twice daily), axitinib was not associated with clinically significant
      QTc prolongation in target populations.

PMID- 25589222
TI  - Therapeutic use of CCR5 antagonists is supported by strong expression of CCR5 on
      CD8(+) T cells in progressive multifocal leukoencephalopathy-associated immune
      reconstitution inflammatory syndrome.

PMID- 25589223
TI  - Danon disease: a phenotypic expression of LAMP-2 deficiency.
AB  - Danon disease is an X-linked disorder clinically characterized by the triad of
      hypertrophic cardiomyopathy, myopathy, and intellectual disability.
      Cardiomyopathy is a severe and life-threatening problem, for which cardiac
      transplantation is the only therapeutic option. The most striking finding in
      muscle biopsy samples is small basophilic granules scattered in myofibers, which
      are in fact small autophagic vacuoles surrounded by membranes with sarcolemmal
      features characterized by the recruitment of sarcolemmal proteins and
      acetylcholine esterase and by the presence of basal lamina on its luminal side.
      The mechanism underlying the formation of these autophagic vacuoles with unique
      sarcolemmal features (AVSF) still remains a mystery and its origin is unknown. In
      heart, cardiomyocytes show dramatically increased vacuolation and degenerative
      features, including myofibrillar disruption and lipofuscin accumulation. In
      brain, pale granular neurons and neurons with lipofuscin-like granules may be
      seen. Danon disease is caused by loss-of-function mutations in the LAMP2 gene,
      which encodes lysosome-associated membrane protein 2 (LAMP-2), a single-spanned
      transmembrane protein localized in the limiting membranes of lysosomes and late
      endosomes. Most mutations lead to splicing defects or protein truncation,
      resulting in a loss of transmembrane and/or cytoplasmic domains, leading to LAMP
      2 protein deficiency. LAMP-2 is required for the maturation of autophagosomes by
      fusion with lysosomes; therefore, LAMP-2 deficiency leads to a failure in
      macroautophagy. There are three LAMP-2 isoforms, LAMP-2A, -2B, and -2C. Clinical
      features of Danon disease are thought to be mediated by loss of the LAMP-2B
      isoform which is the major isoform expressed in muscle. It is also known that
      LAMP-2 plays a role in chaperone-mediated autophagy and RNA- and DNA-targeting
      autophagy. However, the precise pathophysiological mechanism through which LAMP-2
      deficiency causes Danon disease is still not fully understood and its elucidation
      would promote the development of new therapies. 

PMID- 25589225
TI  - Evaluating genetic diversity and constructing core collections of Chinese
      Lentinula edodes cultivars using ISSR and SRAP markers.
AB  - Genetic diversity among 89 Chinese Lentinula edodes cultivars was analyzed by
      inter-simple sequence repeat (ISSR) and sequence-related amplified polymorphism
      (SRAP) markers. A 123 out of 126 ISSR loci (97.62%) and 108 out of 129 SRAP loci
      (83.73%) were polymorphic between two or more strains. A dendrogram constructed
      by cluster analysis based on the ISSR and SRAP markers separated the L. edodes
      strains into two major groups, of which group B was further divided into five
      subgroups. Clustering results also showed a positive correlation with the main
      agronomic traits of the strains, and that strains with similar traits clustered
      together into the same groups or subgroups in most cases. The average coefficient
      of pairwise genetic similarity was 0.820 (range: 0.576-0.988). Compared to the
      wild strains, Chinese L. edodes cultivars indicated a lower level of genetic
      diversity. Two preliminary core collections of L. edodes, Core1 and Core2, were
      established based on the ISSR and SRAP data, respectively. Core1 was constructed
      by the advanced M (maximization) strategy using the PowerCore version 1.0
      software and contained 21 strains, whereas Core2 was created by the allele
      preferred sampling strategy using the cluster method and contained 18 strains.
      Both core collections were highly representative of the genetic diversity of the
      original germplasm, as confirmed by the values of Na (observed number of
      alleles), Ne (effective number of alleles), H (Nei's gene diversity) and I
      (Shannon's information index), as well as results of principal coordinate
      analysis. The loci retention ratio of Core1 (99.61%) was higher than that of
      Core2 (97.65%). Moreover, Core1 contained strains with more types of agronomic
      traits than those in Core2. This study builds the basis for further effective
      protection, management and use of L. edodes germplasm resource. 

PMID- 25589224
TI  - Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and
      intensity modulated radiotherapy (78/82 Gy) for prostate cancer.
AB  - PURPOSE: The purpose of this work was to compare toxicity and cancer control
      between patients with prostate cancer treated using three-dimensional conformal
      radiotherapy (3D-CRT) and those treated using intensity-modulated radiation
      therapy (IMRT). METHODS AND MATERIALS: A total of 553 patients with prostate
      cancer were treated with 3D-CRT 70-74 Gy (3D-CRT 70, 3D-CRT 74) or IMRT 78-82 Gy
      (IMRT 78, IMRT/SIB 82). Late toxicity was scored according to FC-RTOG/LENT
      criteria. Biochemical failure was defined using the Phoenix and ASTRO
      definitions. RESULTS: The 5-year risk of grade 2-4 genitourinary toxicity was
      26.3 % (3D-CRT 70), 27.2 % (3D-CRT 74), 17.3 % (IMRT 78), and 25.1 % (IMRT/SIB
      82) without statistical differences. The 5-year risk of grade 2-4
      gastrointestinal toxicity was 19.4 % (3D-CRT 70), 42.1 % (3D-CRT 74), 20.5 %
      (IMRT 78), and 26.6 % (IMRT/SIB 82). The differences between 3D-CRT 74 and 3D-CRT
      70 and between 3D-CRT 74 and IMRT 78 were statistically significant (log rank p =
      0.03). The 5-year Phoenix PSA relapse-free survival (PSA-RFS) in low-risk,
      intermediate-risk, and high-risk patients treated using 3D-CRT were 89.4, 65.5,
      and 57.8 %, respectively. Patients treated with IMRT achieved the following
      results: 90.9, 89.4, and 83.9 %. Clinical relapse-free survival (C-RFS) in
      patients treated using 3D-CRT vs. IMRT for the aforementioned groups were 94.7
      vs. 100 %, 86.8 vs. 98.6 %, and 84.4 vs. 94.5 %. Disease-free survival (DFS) for
      patients treated using 3D-CRT were 83.1, 70.9, and 71.5 %. The IMRT group reached
      95.8, 89.1, and 87.6 %. The PSA-RFS for intermediate- and high-risk patients were
      statistically significant, while C-RFS and DFS were marginally better.
      CONCLUSION: Dose escalation with IMRT was associated with improved cancer control
      in intermediate- and high-risk patients in comparison with 3D-CRT, without
      compromising toxicity.

PMID- 25589226
TI  - Leptin resistance in diet-induced obesity: the role of hypothalamic inflammation.
AB  - The consumption of Western diets, high in sugar and saturated fat, is a crucial
      contributor to the alarming incidence of obesity and its associated morbidities.
      These diets have been reported to induce an inflammatory response in the
      hypothalamus, which promotes the development of central leptin resistance and
      obesity. This inflammatory signalling involves dynamic changes in the expression
      and activity of several mediators of the innate immune system, including toll
      like receptor 4, IkappaB kinase-beta/nuclear factor-kappaB, c-Jun N-terminal
      kinase, suppressor of cytokine signalling 3 and pro-inflammatory cytokines, as
      well as the induction of endoplasmic reticulum stress and autophagy defect.
      Although the exact cellular mechanisms remain incompletely understood, recent
      evidence suggests that the inflammatory response is at least mediated by
      interactions between neurons and non-neuronal cells such as microglia and
      astrocytes. Current evidence of the contribution of each inflammatory mediator to
      leptin resistance and diet-induced obesity (DIO), including their reciprocal
      interactions and cell-type-specific effects, is reviewed and integrated in a
      conceptual model. Based upon this model and pharmacological intervention studies,
      several inflammatory mediators are proposed to be promising therapeutic targets
      for the treatment of DIO. 

PMID- 25589227
TI  - Updates on quick identification of acetic acid bacteria with a focus on the 16S
      23S rRNA gene internal transcribed spacer and the analysis of cell proteins by
      MALDI-TOF mass spectrometry.
AB  - Acetic acid bacteria have attracted much attention over the past few years, due
      mainly to their metabolic traits that are of interest to the biotechnology
      industry. In addition, it turns out that their ecological habitats are almost
      unlimited since they have been found as symbionts in different insects and also
      as emerging opportunistic human pathogens. Very surprising is the finding that
      they colonize niches considered anaerobic, disproving the generalized statement
      that they are strict aerobes. Since they have taken on different biological roles
      in our environment, more and more people are charged with the task of identifying
      them. However, this turns out to be not always easy, especially if we are using
      phenotypic approaches for identification. A substantial step forward in making
      the identification of acetic acid bacteria easier was made possible using
      molecular biological methods, which have been extensively tested since 2000.
      However, some molecular methods require expensive machines and experienced staff,
      and moreover the level of their discrimination varies. All these factors must be
      considered when selecting the most appropriate approach for identifying acetic
      acid bacteria. With this objective in mind, this review article discusses the
      benefits and drawbacks of molecular biological methods for identification of
      acetic acid bacteria, with a focus on the 16S-23S rRNA gene ITS regions and the
      recently described alternative method for identification of acetic acid bacteria,
      MALDI-TOF MS. 

PMID- 25589228
TI  - Early embryonic and endometrial regulation of tumor necrosis factor and tumor
      necrosis factor receptor 2 in the cattle uterus.
AB  - Tumor necrosis factor (TNF) alpha likely mediates embryomaternal communication in
      mammals. In bovine, we have previously found that the uterine fluid of heifers
      that carried early embryos shows downregulation in the TNF and nuclear factor
      kappaB system. In this work, we assessed the expression of TNF and its receptor
      TNFR2 in the bovine endometrium and embryos during blastocyst development.
      Moreover, to explore the endometrial immune response to early embryos, we
      analyzed the number of CD45 leukocytes in the bovine endometrium. Day 8
      endometrium and blastocyst recovered from animals after transfer of Day 5 embryos
      showed TNF and TNFR2 mRNA transcription and protein colocalization. The presence
      of embryos increased endometrial TNF and TNFR2 protein, whereas endometrial
      leukocytes decreased. Blastocysts exposed to the uterine tract had undetectable
      levels of TNF and lower levels of TNFR2 mRNA. These results suggest that the
      endometrium might lower the TNF concentration in the blastocyst by (1) regulating
      TNF secretion into the uterine fluid and (2) inducing decreased TNF and TNFR2
      mRNA transcription in the embryo. Thus, TNF and TNFR2 might participate in early
      embryomaternal communication. 

PMID- 25589229
TI  - Functional characterization of aquaporins and aquaglyceroporins of the yellow
      fever mosquito, Aedes aegypti.
AB  - After taking vertebrate blood, female mosquitoes quickly shed excess water and
      ions while retaining and concentrating the mostly proteinaceous nutrients.
      Aquaporins (AQPs) are an evolutionary conserved family of membrane transporter
      proteins that regulate the flow of water and in some cases glycerol and other
      small molecules across cellular membranes. In a previous study, we found six
      putative AQP genes in the genome of the yellow fever mosquito, Ae. aegypti, and
      demonstrated the involvement of three of them in the blood meal-induced diuresis.
      Here we characterized AQP expression in different tissues before and after a
      blood meal, explored the substrate specificity of AQPs expressed in the
      Malpighian tubules and performed RNAi-mediated knockdown and tested for changes
      in mosquito desiccation resistance. We found that AQPs are generally down
      regulated 24 hrs after a blood meal. Ae. aegypti AQP 1 strictly transports water,
      AQP 2 and 5 demonstrate limited solute transport, but primarily function as water
      transporters. AQP 4 is an aquaglyceroporin with multiple substrates. Knockdown of
      AQPs expressed in the MTs increased survival of Ae. aegypti under dry conditions.
      We conclude that Malpighian tubules of adult female yellow fever mosquitoes
      utilize three distinct AQPs and one aquaglyceroporin in their osmoregulatory
      functions. 

PMID- 25589230
TI  - Using magnetic levitation for non-destructive quality control of plastic parts.
AB  - Magnetic levitation (MagLev) enables rapid and non-destructive quality control of
      plastic parts. The feasibility of MagLev as a method to: i) rapidly assess
      injection-molded plastic parts for defects during process optimization, ii)
      monitor the degradation of plastics after exposure to harsh environmental
      conditions, and iii) detect counterfeit polymers by density is demonstrated. 

PMID- 25589231
TI  - Training clinicians in how to use patient-reported outcome measures in routine
      clinical practice.
AB  - INTRODUCTION: Patient-reported outcome measures (PROs) were originally developed
      for comparing groups of people in clinical trials and population studies, and the
      results were used to support treatment recommendations or inform health policy,
      but there was not direct benefit for the participants providing PROs data.
      However, as the experience in using those measures increased, it became obvious
      the clinical value in using individual patient PROs profiles in daily practice to
      identify/monitor symptoms, evaluate treatment outcomes and support shared
      decision-making. A key issue limiting successful implementation is clinicians'
      lack of knowledge on how to effectively utilize PROs data in their clinical
      encounters. METHODS: Using a change management theoretical framework, this paper
      describes the development and implementation of three programs for training
      clinicians to effectively use PRO data in routine practice. The training programs
      are in three diverse clinical areas (adult oncology, lung transplant and
      paediatrics), in three countries with different healthcare systems, thus
      providing a rare opportunity to pull out common approaches whilst recognizing
      specific settings. For each program, we describe the clinical and organizational
      setting, the program planning and development, the content of the training
      session with supporting material, subsequent monitoring of PROs use and evidence
      of adoption. The common successful components and practical steps are identified,
      leading to discussion and future recommendations. RESULTS: The results of the
      three training programs are described as the implementation. In the oncology
      program, PRO data have been developed and are currently evaluated; in the lung
      transplant program, PRO data are used in daily practice and the integration with
      electronic patient records is under development; and in the paediatric program,
      PRO data are fully implemented with around 7,600 consultations since the start of
      the implementation. CONCLUSION: Adult learning programs teaching clinicians how
      to use and act on PROs in clinical practice are a key steps in supporting patient
      engagement and participation in shared decision-making. Researchers and
      clinicians from different clinical areas should collaborate to share ideas,
      develop guidelines and promote good practice in patient-centred care.

PMID- 25589232
TI  - The use of cognitive interviews to revise the Quality of Trauma Care Patient
      Reported Experience Measure (QTAC-PREM).
AB  - PURPOSE: The "Quality of Trauma Care Patient-Reported Experience Measure" is the
      first measure of patient experiences with overall injury care. The objective of
      this study was to use cognitive interviews to inform revision of the measure into
      a parsimonious set of items that function as intended, in preparation for
      multicenter testing. METHODS: Concurrent and retrospective cognitive interviews
      with injured patients (n = 17) and family members (n = 13) using semi-structured
      interview guides. Responses were analyzed using thematic analysis. RESULTS: Six
      broad themes were identified and guided revisions: (1) participants did not have
      the information to answer items (n = 9); (2) items were ambiguous or were
      inconsistently interpreted (n = 13); (3) items did not measure the intended
      constructs (n = 6); (4) items included assumptions about healthcare processes (n
      = 4); (5) items measured non-priority aspects of injury care (n = 8); and (6)
      items were redundant (n = 5). Two issues resulted in key conceptual and content
      changes: participants' difficulty to evaluate pre-hospital, emergency department,
      and intensive care unit services due to recall issues and the challenge to
      evaluate the effectiveness and equity of care. In total, 39 items were deleted,
      28 new items developed, and the final instrument included 63 items. CONCLUSIONS:
      Our results informed changes to item content, format, and response options. This
      study highlights key issues to consider when incorporating patient/family
      perspectives into quality measurement, most notably, that few participants can
      assess the quality of care in the pre-hospital and emergency department phases of
      care and that novel methods are needed to evaluate the effectiveness and equity
      of care.

PMID- 25589233
TI  - Veteran, primary care provider, and specialist satisfaction with electronic
      consultation.
AB  - BACKGROUND: Access to specialty care is challenging for veterans in rural
      locations. To address this challenge, in December 2009, the Veterans Affairs (VA)
      Pittsburgh Healthcare System (VAPHS) implemented an electronic consultation (e
      consult) program to provide primary care providers (PCPs) and patients with
      enhanced specialty care access. OBJECTIVE: The aim of this quality improvement
      (QI) project evaluation was to: (1) assess satisfaction with the e-consult
      process, and (2) identify perceived facilitators and barriers to using the e
      consult program. METHODS: We conducted semistructured telephone interviews with
      veteran patients (N=15), Community Based Outpatient Clinic (CBOC) PCPs (N=15),
      and VA Pittsburgh specialty physicians (N=4) who used the e-consult program
      between December 2009 to August 2010. Participants answered questions regarding
      satisfaction in eight domains and identified factors contributing to their
      responses. RESULTS: Most participants were white (patients=87%; PCPs=80%;
      specialists=75%) and male (patients=93%; PCPs=67%; specialists=75%). On average,
      patients had one e-consult (SD 0), PCPs initiated 6 e-consults (SD 6), and VAPHS
      specialists performed 17 e-consults (SD 11). Patients, PCPs, and specialty
      physicians were satisfied with e-consults median (range) of 5.0 (4-5) on 1-5
      Likert-scale, 4.0 (3-5), and 3.5 (3-5) respectively. The most common reason why
      patients and specialists reported increased overall satisfaction with e-consults
      was improved communication, whereas improved timeliness of care was the most
      common reason for PCPs. Communication was the most reported perceived barrier and
      facilitator to e-consult use. CONCLUSIONS: Veterans and VA health care providers
      were satisfied with the e-consult process. Our findings suggest that while the
      reasons for satisfaction with e-consult differ somewhat for patients and
      physicians, e-consult may be a useful tool to improve VA health care system
      access for rural patients.

PMID- 25589236
TI  - Simultaneous ultrasound-assisted water extraction and beta-cyclodextrin
      encapsulation of polyphenols from Mangifera indica stem bark in counteracting
      TNFalpha-induced endothelial dysfunction.
AB  - This study proposes an alternative technique to prevent heat degradation induced
      by classic procedures of bioactive compound extraction, comparing classical
      maceration/decoction in hot water of polyphenols from Mango (Mangifera indica L.)
      (MI) with ultrasound-assisted extraction (UAE) in a water solution of beta
      cyclodextrin (beta-CD) at room temperature and testing their biological activity
      on TNFalpha-induced endothelial dysfunction. Both extracts counteracted TNFalpha
      effects on EAhy926 cells, down-modulating interleukin-6, interleukin-8,
      cyclooxygenase-2 and intracellular adhesion molecule-1, while increasing
      endothelial nitric oxide synthase levels. beta-CD extract showed higher efficacy
      in improving endothelial function. These effects were abolished after pre
      treatment with the oestrogen receptor inhibitor ICI1182,780. Moreover, the beta
      CD extract induced Akt activation and completely abolished the TNFalpha-induced
      p38MAPK phosphorylation. UAE and beta-CD encapsulation provide an efficient
      extraction protocol that increases polyphenol bioavailability. Polyphenols from
      MI play a protective role on endothelial cells and may be further considered as
      oestrogen-like molecules with vascular protective properties. 

PMID- 25589237
TI  - Long-term effects of continuous theta-burst stimulation in visuospatial neglect.
AB  - OBJECTIVE: To investigate whether the efficacy of continuous theta-burst
      stimulation (cTBS) for improving visuospatial neglect can be enhanced by
      providing more days of stimulation and more stimulation trains per day. METHODS:
      In a prospective study, right-handed patients with right hemisphere stroke and
      visuospatial neglect were randomized to cTBS or sham cTBS treatment for 2 weeks
      and were followed up for 4 weeks. The cTBS group received active cTBS over the
      posterior parietal cortex of the unaffected hemisphere, combined with
      conventional rehabilitation therapy. Changes in scores for two paper-pencil tests
      for visuospatial neglect (star cancellation and line bisection) were evaluated.
      RESULTS: In each group, 10 patients completed follow up. Compared with the sham
      group, star cancellation test scores in the cTBS group were improved by 37.03% at
      the end of treatment and by 47.21% after 4 weeks' follow up, and the line
      bisection score improved by 21.37% at the end of treatment and by 35.99% after 4
      weeks' follow up. CONCLUSIONS: These results suggest that the efficacy of cTBS in
      visuospatial neglect can be enhanced and prolonged by increasing the days of
      stimulation and the number of stimulation trains per day over the left posterior
      parietal cortex.

PMID- 25589239
TI  - Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) promotes EIAV
      replication and infectivity.
AB  - Adenosine deaminases that act on RNA (ADARs) have been reported to be functional
      on various viruses. ADAR1 may exhibit antiviral or proviral activity depending on
      the type of virus. Human immunodeficiency virus (HIV)-1 is the most well-studied
      lentivirus with respect to its interaction with ADAR1, and variable results have
      been reported. In this study, we demonstrated that equine ADAR1 (eADAR1) was a
      positive regulator of equine infectious anemia virus (EIAV), another lentivirus
      of the Retroviridae family. First, eADAR1 significantly promoted EIAV
      replication, and the enhancement of viral protein expression was associated with
      the long terminal repeat (LTR) and Rev response element (RRE) regions. Second,
      the RNA binding domain 1 of eADAR1 was essential only for enhancing LTR-mediated
      gene expression. Third, in contrast with APOBEC proteins, which have been shown
      to reduce lentiviral infectivity, eADAR1 increased the EIAV infectivity. This
      study indicated that eADAR1 was proviral rather than antiviral for EIAV. 

PMID- 25589240
TI  - Pathogenic prion protein fragment (PrP106-126) promotes human immunodeficiency
      virus type-1 infection in peripheral blood monocyte-derived macrophages.
AB  - Transfusion of blood and blood products contaminated with the pathogenic form of
      prion protein Prp(sc), thought to be the causative agent of variant a Creutzfeldt
      Jakob disease (vCJD), may result in serious consequences in recipients with a
      compromised immune system, for example, as seen in HIV-1 infection. In the
      present study, we demonstrate that treatment of peripheral blood monocyte-derived
      macrophages (MDM) with PrP106-126, a synthetic domain of PrP(sc) that has
      intrinsic functional activities related to the full-length protein, markedly
      increased their susceptibility to HIV-1 infection, induced cytokine secretion,
      and enhanced their migratory behavior in response to N-formyl-l-methionyl-l
      leucyl-l-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence
      of PrP106-126 showed large cell clusters indicative of cellular activation.
      Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin
      dependent kinase inhibitor olomoucine attenuated PrP106-126-induced altered MDM
      functions. These findings delineate a previously undefined functional role of
      PrP106-126-mediated host cell response in promoting HIV-1 pathogenesis. 

PMID- 25589238
TI  - An expanded taxonomy of hepatitis C virus genotype 6: Characterization of 22 new
      full-length viral genomes.
AB  - We characterized the full-length genomes of 22 hepatitis C virus genotype 6 (HCV
      6) isolates: 10 from Vietnam (classified into subtypes 6e, 6h, 6p, 6r, 6s, and
      6u), one from China (confirmed as a new subtype 6xd), and 11 from the Lao PDR
      (representing a new subtype 6xe plus eight novel variants). With these 22 new
      genomes, HCV-6 now has a diverse and extended taxonomic structure, comprised of
      28 assigned subtypes (denoted 6a-6xe) and 27 unassigned lineages, all of which
      have been represented by full-length genomes. Our phylogenetic analyses also
      included many partially-sequenced novel variants of HCV-6 from Lao PDR. This
      revealed that Lao HCV isolates are genetically very diverse and are
      phylogenetically distributed in multiple lineages within genotype 6. Our results
      suggest that HCV-6 has been maintained in Laos, a landlocked country, since the
      common ancestor of genotype 6 and indicates historical dispersal of HCV-6 across
      Southeast Asia. 

PMID- 25589241
TI  - Polyomavirus T antigens activate an antiviral state.
AB  - Ectopic expression of Simian Virus 40 (SV40) large T antigen (LT) in mouse
      embryonic fibroblasts (MEFs) increased levels of mRNAs encoding interferon
      stimulated genes (ISGs). The mechanism by which T antigen increases levels of
      ISGs in MEFs remains unclear. We present evidence that expression of T antigen
      from SV40, Human Polyomaviruses BK (BKV) or JC (JCV) upregulate production of
      ISGs in MEFs, and subsequently result in an antiviral state, as determined by
      inhibition of VSV or EMCV growth. The first 136 amino acids of LT are sufficient
      for these activities. Furthermore, increased ISG expression and induction of the
      antiviral state requires STAT1. Finally, the RB binding motif of LT is necessary
      for activation of STAT1. We conclude that the induction of the STAT1 mediated
      innate immune response in MEFs is a common feature shared by SV40, BKV and JCV. 

PMID- 25589242
TI  - Systematic assessment of the correlations of household income with infectious,
      biochemical, physiological, and environmental factors in the United States, 1999
      2006.
AB  - A fuller understanding of the social epidemiology of disease requires an extended
      description of the relationships between social factors and health indicators in
      a systematic manner. In the present study, we investigated the correlations
      between income and 330 indicators of physiological, biochemical, and
      environmental health in participants in the US National Health and Nutrition
      Examination Survey (NHANES) (1999-2006). We combined data from 3 survey waves (n
      = 249-23,649 for various indicators) to search for linear and nonlinear
      (quadratic) correlates of income, and we validated significant (P < 0.00015)
      correlations in an independent testing data set (n = 255-7,855). We validated 66
      out of 330 factors, including infectious (e.g., hepatitis A), biochemical (e.g.,
      carotenoids, high-density lipoprotein cholesterol), physiological (e.g., upper
      leg length), and environmental (e.g., lead, cotinine) measures. We found only a
      modest amount of association modification by age, race/ethnicity, and gender, and
      there was no association modification for blacks. The present study is
      descriptive, not causal. We have shown in our systematic investigation the
      crucial place income has in relation to health risk factors. Future research can
      use these correlations to better inform theory and studies of pathways to
      disease, as well as utilize these findings to understand when confounding by
      income is most likely to introduce bias. 

PMID- 25589243
TI  - A cautionary note about estimating effects of secondary exposures in cohort
      studies.
AB  - Cohort studies are often enriched for a primary exposure of interest to improve
      cost-effectiveness, which presents analytical challenges not commonly discussed
      in epidemiology. In this paper, we use causal diagrams to represent exposure
      enriched cohort studies, illustrate a scenario wherein the risk ratio for the
      effect of a secondary exposure on an outcome is biased, and propose an analytical
      method for correcting for such bias. In our motivating example, maternal smoking
      (Z) is a cause of fetal growth restriction (X), which subsequently affects
      preterm birth (Y) (i.e., Z -> X -> Y); strong positive associations exist between
      both Z, X and X, Y; and enrichment for X increases its prevalence from 10% to
      50%. In the X-enriched cohort, unadjusted and X-adjusted analyses lead to bias in
      the risk ratio for the total effect of Z on Y. After application of inverse
      probability weights, the bias is corrected, with a small loss of efficiency in
      comparison with a same-sized study without X-enrichment. With increasing interest
      in conducting secondary analyses to reduce research costs, caution should be
      employed when analyzing studies that have already been enriched, intentionally or
      unintentionally, for a primary exposure of interest. Causal diagrams can help
      identify scenarios in which secondary analyses may be biased. Inverse probability
      weights can be used to remove the bias. 

PMID- 25589244
TI  - LIMS2 mutations are associated with a novel muscular dystrophy, severe
      cardiomyopathy and triangular tongues.
AB  - Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of genetic
      disorders leading to progressive muscle degeneration and often associated with
      cardiac complications. We present two adult siblings with childhood-onset of
      weakness progressing to a severe quadriparesis with the additional features of
      triangular tongues and biventricular cardiac dysfunction. Whole exome sequencing
      identified compound heterozygous missense mutations that are predicted to be
      pathogenic in LIMS2. Biopsy of skeletal muscle demonstrated disrupted
      immunostaining of LIMS2. This is the first report of mutations in LIMS2 and
      resulting disruption of the integrin linked kinase (ILK)-LIMS-parvin complex
      associated with LGMD. 

PMID- 25589245
TI  - Recurrent white thrombi formation in hemodialysis tubing: a case report.
AB  - BACKGROUND: While the appearance of red clots in the dialyzer is a common
      phenomenon in every hemodialysis unit, the occurrence of white thrombi in the
      tubing is relatively rare. CASE PRESENTATION: We describe an adolescent male with
      recurrent white thrombi formation in the hemodialysis tubing. This patient had
      chronic renal failure from focal segmental glomerulosclerosis, but was no longer
      nephrotic at the time of the thrombi formation. He had a history of recurrent
      thrombosis of his vascular access. However, no pro-thrombotic risk factors could
      be identified. White particulate matter, measuring 1 to 3mm in size, and adherent
      to the arterial and venous blood tubing lines was found during the rinse back of
      a hemodialysis session. This was associated with a 60% decrease in his platelet
      count. Light microscopic examination of the deposits revealed the presence of
      platelet aggregates. He subsequently developed thrombosis of his arteriovenous
      graft six hours later. The white thrombi recurred at the next dialysis session,
      as well as six months later. These episodes occurred regardless of the type of
      dialysis machine or tubing, and appeared to resolve with an increase in heparin
      dose. CONCLUSION: Recurrent white thrombi formation can occur in the hemodialysis
      tubing of a patient with no identifiable pro-thrombotic factors. The white
      thrombi may be a harbinger of arteriovenous graft thrombosis and may be prevented
      by an increase in heparin dose.

PMID- 25589246
TI  - Patients are being discharged to die in care homes, conference hears.

PMID- 25589247
TI  - Relationship between nucleosome positioning and progesterone-induced alternative
      splicing in breast cancer cells.
AB  - Splicing of mRNA precursors can occur cotranscriptionally and it has been
      proposed that chromatin structure influences splice site recognition and
      regulation. Here we have systematically explored potential links between
      nucleosome positioning and alternative splicing regulation upon progesterone
      stimulation of breast cancer cells. We confirm preferential nucleosome
      positioning in exons and report four distinct profiles of nucleosome density
      around alternatively spliced exons, with RNA polymerase II accumulation closely
      following nucleosome positioning. Hormone stimulation induces switches between
      profile classes, correlating with a subset of alternative splicing changes.
      Hormone-induced exon inclusion often correlates with higher nucleosome occupancy
      at the exon or the preceding intronic region and with higher RNA polymerase II
      accumulation. In contrast, exons skipped upon hormone stimulation display low
      nucleosome densities even before hormone treatment, suggesting that chromatin
      structure primes alternative splicing regulation. Skipped exons frequently harbor
      binding sites for hnRNP AB, a hormone-induced splicing regulator whose knock down
      prevents some hormone-induced skipping events. Collectively, our results argue
      that a variety of chromatin architecture mechanisms can influence alternative
      splicing decisions.

PMID- 25589248
TI  - Unexpected selection to retain high GC content and splicing enhancers within
      exons of multiexonic lncRNA loci.
AB  - If sequencing was possible only for genomes, and not for RNAs or proteins, then
      functional protein-coding exons would be recognizable by their unusual patterns
      of nucleotide composition, specifically a high GC content across the body of
      exons, and an unusual nucleotide content near their edges. RNAs and proteins can,
      of course, be sequenced but the extent of functionality of intergenic long
      noncoding RNAs (lncRNAs) remains under question owing to their low nucleotide
      conservation. Inspired by the nucleotide composition patterns of protein-coding
      exons, we sought evidence for functionality across lncRNA loci from diverse
      species. We found that such patterns across multiexonic lncRNA loci mirror those
      of proteincoding genes, although to a lesser degree: Specifically, compared with
      introns, lncRNA exons are GC rich. Additionally we report evidence for the action
      of purifying selection to preserve exonic splicing enhancers within human
      multiexonic lncRNAs and nucleotide composition in fruit fly lncRNAs. Our findings
      provide evidence for selection for more efficient rates of transcription and
      splicing within lncRNA loci. Despite only a minor proportion of their RNA bases
      being constrained, multiexonic intergenic lncRNAs appear to require accurate
      splicing of their exons to transact their function.

PMID- 25589249
TI  - Is drug-eluting bead transcatheter arterial chemoembolization (TACE) associated
      with better tumor response than conventional TACE in meta-analysis?

PMID- 25589251
TI  - Role of disorder in finite-amplitude shear of a 2D jammed material.
AB  - A material's response to small but finite deformations can reveal the roots of
      its response to much larger deformations. Here, we identify commonalities in the
      responses of 2D soft jammed solids with different amounts of disorder. We
      cyclically shear the materials while tracking their constituent particles, in
      experiments that feature a stable population of repeated structural relaxations.
      Using bidisperse particle sizes creates a more amorphous material, while
      monodisperse sizes yield a more polycrystalline one. We find that the materials'
      responses are very similar, both at the macroscopic, mechanical level and in the
      microscopic motions of individual particles. However, both locally and in bulk,
      crystalline arrangements of particles are stiffer (greater elastic modulus) and
      less likely to rearrange. Our work supports the idea of a common description for
      the responses of a wide array of materials. 

PMID- 25589252
TI  - An UPLC-MS/MS method for the analysis of glimepiride and fluoxetine in human
      plasma.
AB  - A sensitive and rapid ultra performance liquid chromatography tandem mass
      spectrometry (UPLC-MS/MS) method was developed to determine glimepiride (GPD) and
      fluoxetine (FLU) in human plasma using diazepam as the internal standard (IS)
      simultaneously. The presented method used an Acquity UPLC BEH C18 column for
      chromatographic separation with tandem mass spectrometric detection on a
      QTrap5500 mass spectrometer operated in positive ESI mode. The mobile phase is a
      mixture of acetonitrile and 1% formic acid in water with gradient elution at a
      flow rate of 0.40mL/min. The GPD, FLU and IS were eluted at 1.46, 1.27 and
      1.39min, respectively. The MRM transitions of m/z 491.3->126.3 and m/z 310.5
      >148.1 were used to quantify for GPD and FLU, respectively. The linearity of this
      method was found to be within the concentration range of 2.5-300ng/mL and 0.1
      20ng/mL for GPD and FLU in human plasma, respectively. The intra- and inter-day
      precision (RSD%) were less than 10.3% and accuracy (RE%) was within +/-7.3%. The
      matrix effect were 95.3-100.7% for GPD and FLU. GPD and FLU were sufficiently
      stable under all relevant analytical conditions. The method was also successfully
      applied to the clinical samples after a single oral dose of 2mg GLP and 40mg FLU
      in patients. 

PMID- 25589253
TI  - Dynamic pH junction-sweeping technique for on-line concentration of acidic amino
      acids in human serum by capillary electrophoresis with indirect UV detection.
AB  - Glutamic acid (Glu) and aspartic acid (Asp), as two important neurotransmitters,
      have been the focus of increasingly intense research over the past several years.
      Glu and Asp are present in biological fluids such as serum at trace levels, but
      complex components in biological matrices make it difficult to determine them in
      biological samples. In this paper, a sensitive and simple method coupled with
      indirect UV detection, using benzoic acid (BA) as the UV-absorbing probe, was
      developed and validated for the quantitative determination of Glu and Asp in
      human serum and Compound Amino Acid Injection-18 AA. The method combines a
      dynamic pH junction with a sweeping technique using beta-cyclodextrin (beta-CD)
      as the complexing agent for sweeping. Employing this proposed method, low
      detection limits of 0.061MUg/mL for Glu and 0.032MUg/mL for Asp were obtained.
      The sensitivity was improved 30- and 55-fold for Glu and Asp compared to
      conventional CE method. Standard curves were linear (r>0.999) over the
      concentration range of 0.1-8.0MUg/mL. To further improve the resolution of Asp
      from interfering substances in human serum, 6% (v/v) methanol was added to the
      sample matrix, and resulted in the detection limits of 0.125MUg/mL for Glu and
      0.057MUg/mL for Asp. With a simple precipitation of protein, the method has been
      successfully applied to the analysis of human serum, and the recoveries (82% for
      Glu and 87% for Asp) were achieved with relative standard deviations of 1.9% and
      2.0%, respectively. 

PMID- 25589254
TI  - Development and validation of a high-performance liquid chromatography
      fluorescence detection method for the accurate quantification of colistin in
      human plasma.
AB  - Recently, colistin has become one of the most important drugs for treating
      infections caused by multidrug-resistant Gram-negative bacteria. Therapeutic drug
      monitoring is recommended to ensure the safety and efficacy of colistin and to
      improve clinical outcomes. This study developed an accurate and sensitive high
      performance liquid chromatography-fluorescence detection (HPLC-FLD) method for
      the quantification of colistin in human plasma. The sample preparation included
      protein precipitation using trichloroacetic acid (TCA) and methanol, followed by
      in-solid phase extraction (In-SPE) derivatization with 9-fluorenylmethyl
      chloroformate (FMOC-Cl). A Poroshell 120 EC-C18 2.1*100mm (2.7MUm) column was
      used in the HPLC method with a mobile phase composed of acetonitrile (ACN),
      tetrahydrofuran (THF), and deionized (DI) water (82%, 2%, 16% (v/v),
      respectively). Polymyxin B1 was used as the internal standard. The total analysis
      time was 22min under optimal separation conditions. The HPLC-FLD method was
      validated over a therapeutic range of 0.3-6.0MUgmL(-1). The intra-day and inter
      day precisions for colistin A and colistin B were below 9.9% and 4.5% relative
      standard deviations, respectively. The accuracy test results were between 100.2
      and 118.4%. The extraction recoveries were between 81.6 and 94.1%. The method was
      linear over the test range, with a 0.9991 coefficient of determination. The limit
      of detection was 0.1MUgmL(-1). The validated HPLC-FLD method was successfully
      applied to quantify the colistin concentrations in 2 patient samples for
      therapeutic drug monitoring. 

PMID- 25589255
TI  - [PMIM]Br@TiO2 nanocomposite reinforced hollow fiber solid/liquid phase
      microextraction: an effective extraction technique for measurement of
      benzodiazepines in hair, urine and wastewater samples combined with high
      performance liquid chromatography.
AB  - A new design of hollow fiber solid-liquid phase microextraction (HF-SLPME) was
      developed for the determination of benzodiazepines (BZPs) in hair, urine and
      wastewater. The membrane extraction with 1-pentyl-3-methylimidazolium bromide
      coated titanium dioxide ([PMIM]Br@TiO2) sorbent used in this research is a two
      phase supported membrane extraction consisting of an aqueous (donor phase), and n
      octanol/nano [PMIM]Br@TiO2 (acceptor phase) system operated in direct immersion
      sampling mode. The 1-pentyl-3-methylimidazolium bromide (ionic liquid) coated
      nano TiO2 dispersed in the organic solvent (n-octanol) is held into a porous
      membrane supported by capillary forces and sonification. It is in contact with
      the feed phase, which is the aqueous sample. The experimental setup is very
      simple and highly affordable. The hollow fiber is disposable, so single use of
      the fiber reduces the risk of cross-contamination and carry-over problems. The
      proposed method allows the very effective and enriched recuperation of BZPs into
      one single extract. In order to obtain high extraction efficiency of the analytes
      using this novel sorbent, the main parameters were optimized. Under the optimized
      extraction conditions, the method showed good linearity (0.05-6000ngmL(-1)), low
      limits of detection (0.08-0.5ngmL(-1)) and good enrichment (533-1190). 

PMID- 25589256
TI  - Capillary electrophoresis-mass spectrometry determination of morphine and its
      isobaric glucuronide metabolites.
AB  - The determination of morphine and its isobaric metabolites morphine-3-beta-d
      glucuronide (M3G) and morphine-6-beta-d-glucuronide (M6G) is useful for
      therapeutic drug monitoring and forensic identification of drug use. In
      particular, capillary electrophoresis with mass spectrometry (CE-MS) represents
      an attractive tool for opioid analysis. Whereas volatile background electrolytes
      in CE often improve electrospray ionization for coupled MS detection, such
      electrolytes may reduce CE separation efficiency and resolution. To better
      understand the effects of background electrolyte (BGE) composition on separation
      efficiency and detection sensitivity, this work compares and contrasts method
      development for both volatile (ammonium formate and acetate) and nonvolatile
      (ammonium phosphate and borate) buffers. Peak efficiencies and migration times
      for morphine and morphine metabolites were optimal with a 25mM ammonium borate
      buffer (pH=9.5) although greater sensitivities were achieved in the ammonium
      formate buffer. Optimized CE methods allowed for the resolution of the isobaric
      morphine metabolites prior to high mass accuracy, electrospray ionization
      quadrupole time-of-flight (ESI-QTOF) MS detection applicable to the analysis of
      urine samples in under seven minutes. Urine sample preparation required only a 10
      fold dilution with BGE prior to analysis. Limits of detection (LOD) in normal
      human urine were found to be 1.0MUg/mL for morphine and 2.5MUg/mL for each of M3G
      and M6G by CE-ESI-QTOF-MS. These LODs were comparable to those for CE-UV analysis
      of opioid standards in buffer, whereas CE-ESI-QTOF-MS analysis of opioid
      standards in buffer yielded LODs an order of magnitude lower. Patient urine
      samples (N=12) were analyzed by this new CE-ESI-QTOF-MS method and no significant
      difference in total morphine content relative to prior liquid chromatography-mass
      spectrometry (LC-MS) results was found as per a paired-t test at the 99%
      confidence level. Whereas the LC-MS method applied to these samples determined
      only total morphine content, this new CE-ESI-QTOF-MS method allowed for species
      differentiation in addition to total morphine determination. By this method, it
      was found that M3G and M6G metabolites were present in a 5:1 concentration ratio,
      on average, in patient samples. Therefore, the CE-ESI-QTOF-MS method not only
      allows for total morphine concentration determination comparable to established
      LC-MS methods, but also allows for differentiation between morphine and its trace
      glucuronides, yielding additional biochemical information about drug metabolism. 

PMID- 25589257
TI  - An UPLC-MS/MS method for quantitative profiling of bile acids in sea lamprey
      plasma and tissues.
AB  - Bile acids (BAs) have recently gained more attention because of their diverse
      roles from digestion to signaling. Simultaneous analyses of various BAs in
      biological samples are challenging due to their structural similarity, relatively
      low concentrations, and the presence of isomeric forms. In this study, we report
      a simple and sensitive UPLC-MS/MS method for simultaneous quantifications of 13
      BAs including four unique sea lamprey BAs in sea lamprey plasma, liver,
      intestine, and gills. A straightforward protein precipitation (PPT) method was
      used to extract BAs from the biological samples. Separation of all target
      analytes was achieved on a reverse-phase UPLC column in 15min, and detection was
      carried out on MS/MS with ESI in the negative ionization mode. This method was
      validated regarding its linearity, limits of detection (LOD), recovery, matrix
      effect, reproducibility, accuracy and precision. Significant improvements
      compared to previous LC-MS/MS methods were observed as a result of the
      application of UPLC and extensive optimization of experimental conditions. The
      method showed excellent linearity with high regression coefficients (>0.99) over
      a range of 0.5-1000ng/mL and LODs ranged from 0.009 to 0.11ng/mL. The
      applications of the developed method demonstrated that it simultaneously
      determined all target BAs in different biological sample matrices with excellent
      sensitivity, selectivity and reproducibility. 

PMID- 25589258
TI  - Evaluation of a rapid method for the therapeutic drug monitoring of aliskiren,
      enalapril and its active metabolite in plasma and urine by UHPLC-MS/MS.
AB  - Given the increasing popularity of aliskiren, particularly in combination with
      angiotensin converting enzyme inhibitor (e.g. enalapril), it is important to
      determine whether its use in combination with these agents is associated with
      potentially life threatening safety events. Analytical methods for the
      simultaneous determination of both drugs in plasma and urine utilized in clinical
      studies on efficacy and safety have not been fully described in the literature.
      In this work, a new, fast and reliable method using a digitally controlled
      microextraction by packed sorbent (eVol((r))-MEPS) followed by ultra-high
      performance liquid chromatography (UHPLC) coupled with tandem mass spectrometry
      (MS/MS) was developed and validated to quantify an aliskiren, enalapril and its
      active metabolite in both human plasma and urine. Chromatographic separation was
      accomplished on a Poroshell 120 EC-C18 column with a gradient elution system
      consisting of 0.1% formic acid in water and acetonitrile (1.5min of total
      analysis). Detection was performed by multiple reaction monitoring (MRM) mode
      using electrospray ionization in the positive ion mode. This assay method has
      been fully validated in terms of selectivity, linearity, accuracy, precision,
      stability, recovery and matrix effect. The developed method can be applied to the
      routine determination of selected compounds in human plasma and urine and can be
      useful to elucidate the mechanisms of the potential risks triggered by the
      combination of aliskiren and enalapril as well as its active metabolite
      enalaprilat. 

PMID- 25589259
TI  - NHS can perform well against the private sector without compromising its core
      values.

PMID- 25589262
TI  - Peripheral and central effects of circulating catecholamines.
AB  - Physical challenges, emotional arousal, increased physical activity, or changes
      in the environment can evoke stress, requiring altered activity of visceral
      organs, glands, and smooth muscles. These alterations are necessary for the
      organism to function appropriately under these abnormal conditions and to restore
      homeostasis. These changes in activity comprise the "fight-or-flight" response
      and must occur rapidly or the organism may not survive. The rapid responses are
      mediated primarily via the catecholamines, epinephrine, and norepinephrine,
      secreted from the adrenal medulla. The catecholamine neurohormones interact with
      adrenergic receptors present on cell membranes of all visceral organs and smooth
      muscles, leading to activation of signaling pathways and consequent alterations
      in organ function and smooth muscle tone. During the "fight-or-flight response,"
      the rise in circulating epinephrine and norepinephrine from the adrenal medulla
      and norepinephrine secreted from sympathetic nerve terminals cause increased
      blood pressure and cardiac output, relaxation of bronchial, intestinal and many
      other smooth muscles, mydriasis, and metabolic changes that increase levels of
      blood glucose and free fatty acids. Circulating catecholamines can also alter
      memory via effects on afferent sensory nerves impacting central nervous system
      function. While these rapid responses may be necessary for survival, sustained
      elevation of circulating catecholamines for prolonged periods of time can also
      produce pathological conditions, such as cardiac hypertrophy and heart failure,
      hypertension, and posttraumatic stress disorder. In this review, we discuss the
      present knowledge of the effects of circulating catecholamines on peripheral
      organs and tissues, as well as on memory in the brain.

PMID- 25589261
TI  - Simple phenotypic sweeps hide complex genetic changes in populations.
AB  - Changes in allele frequencies and the fixation of beneficial mutations are
      central to evolution. The precise relationship between mutational and phenotypic
      sweeps is poorly described however, especially when multiple alleles are
      involved. Here, we investigate these relationships in a bacterial population over
      60 days in a glucose-limited chemostat in a large population. High coverage
      metagenomic analysis revealed a disconnection between smooth phenotypic sweeps
      and the complexity of genetic changes in the population. Phenotypic adaptation
      was due to convergent evolution and involved soft sweeps by 7-26 highly
      represented alleles of several genes in different combinations. Allele
      combinations spread from undetectably low baselines, indicating that minor
      subpopulations provide the basis of most innovations. A hard sweep was also
      observed, involving a single combination of rpoS, mglD, malE, sdhC, and malT
      mutations sweeping to greater than 95% of the population. Other mutant genes
      persisted but at lower abundance, including hfq, consistent with its demonstrated
      frequency-dependent fitness under glucose limitation. Other persistent, newly
      identified low-frequency mutations were in the aceF, galF, ribD and asm genes, in
      noncoding regulatory regions, three large indels and a tandem duplication; these
      were less affected by fluctuations involving more dominant mutations indicating
      separate evolutionary paths. Our results indicate a dynamic subpopulation
      structure with a minimum of 42 detectable mutations maintained over 60 days. We
      also conclude that the massive population-level mutation supply in combination
      with clonal interference leads to the soft sweeps observed, but not to the
      exclusion of an occasional hard sweep.

PMID- 25589265
TI  - Human locomotion and heat loss: an evolutionary perspective.
AB  - Humans are unique in many respects including being furless, striding bipeds that
      excel at walking and running long distances in hot conditions. This review
      summarizes what we do and do not know about the evolution of these
      characteristics, and how they are related. Although many details remain poorly
      known, the first hominins (species more closely related to humans than to
      chimpanzees) apparently diverged from the chimpanzee lineage because of selection
      for bipedal walking, probably because it improved their ability to forage
      efficiently. However, because bipedal hominins are necessarily slow runners,
      early hominins in open habitats likely benefited from improved abilities to dump
      heat in order to forage safely during times of peak heat when predators were
      unable to hunt them. Endurance running capabilities evolved later, probably as
      adaptations for scavenging and then hunting. If so, then there would have been
      strong selection for heat-loss mechanisms, especially sweating, to persistence
      hunt, in which hunters combine endurance running and tracking to drive their prey
      into hyperthermia. As modern humans dispersed into a wide range of habitats over
      the last few hundred thousand years, recent selection has helped populations cope
      better with a broader range of locomotor and thermoregulatory challenges, but all
      humans remain essentially adapted for long distance locomotion rather than speed,
      and to dump rather than retain heat.

PMID- 25589250
TI  - Nitrite reduction by molybdoenzymes: a new class of nitric oxide-forming nitrite
      reductases.
AB  - Nitric oxide (NO) is a signalling molecule involved in several physiological
      processes, in both prokaryotes and eukaryotes, and nitrite is being recognised as
      an NO source particularly relevant to cell signalling and survival under
      challenging conditions. The "non-respiratory" nitrite reduction to NO is carried
      out by "non-dedicated" nitrite reductases, making use of metalloproteins present
      in cells to carry out other functions, such as several molybdoenzymes (a new
      class of nitric oxide-forming nitrite reductases). This minireview will highlight
      the physiological relevance of molybdenum-dependent nitrite-derived NO formation
      in mammalian, plant and bacterial signalling (and other) pathways. The mammalian
      xanthine oxidase/xanthine dehydrogenase, aldehyde oxidase, mitochondrial
      amidoxime-reducing component, plant nitrate reductase and bacterial aldehyde
      oxidoreductase and nitrate reductases will be considered. The nitrite reductase
      activity of each molybdoenzyme will be described and the review will be oriented
      to discuss the feasibility of the reactions from a (bio)chemical point of view.
      In addition, the molecular mechanism proposed for the molybdenum-dependent
      nitrite reduction will be discussed in detail. 

PMID- 25589263
TI  - Human cardiovascular responses to passive heat stress.
AB  - Heat stress increases human morbidity and mortality compared to normothermic
      conditions. Many occupations, disease states, as well as stages of life are
      especially vulnerable to the stress imposed on the cardiovascular system during
      exposure to hot ambient conditions. This review focuses on the cardiovascular
      responses to heat stress that are necessary for heat dissipation. To accomplish
      this regulatory feat requires complex autonomic nervous system control of the
      heart and various vascular beds. For example, during heat stress cardiac output
      increases up to twofold, by increases in heart rate and an active maintenance of
      stroke volume via increases in inotropy in the presence of decreases in cardiac
      preload. Baroreflexes retain the ability to regulate blood pressure in many, but
      not all, heat stress conditions. Central hypovolemia is another cardiovascular
      challenge brought about by heat stress, which if added to a subsequent central
      volumetric stress, such as hemorrhage, can be problematic and potentially
      dangerous, as syncope and cardiovascular collapse may ensue. These combined
      stresses can compromise blood flow and oxygenation to important tissues such as
      the brain. It is notable that this compromised condition can occur at cardiac
      outputs that are adequate during normothermic conditions but are inadequate in
      heat because of the increased systemic vascular conductance associated with
      cutaneous vasodilation. Understanding the mechanisms within this complex
      regulatory system will allow for the development of treatment recommendations and
      countermeasures to reduce risks during the ever-increasing frequency of severe
      heat events that are predicted to occur.

PMID- 25589267
TI  - Autonomic regulation of hepatic glucose production.
AB  - Glucose produced by the liver is a major energy source for the brain. Considering
      its critical dependence on glucose, it seems only natural that the brain is
      capable of monitoring and controlling glucose homeostasis. In addition to
      neuroendocrine pathways, the brain uses the autonomic nervous system to
      communicate with peripheral organs. Within the brain, the hypothalamus is the key
      region to integrate signals on energy status, including signals from lipid,
      glucose, and hormone sensing cells, with afferent neural signals from the
      internal and external milieu. In turn, the hypothalamus regulates metabolism in
      peripheral organs, including the liver, not only via the anterior pituitary gland
      but also via multiple neuropeptidergic pathways in the hypothalamus that have
      been identified as regulators of hepatic glucose metabolism. These pathways
      comprise preautonomic neurons projecting to nuclei in the brain stem and spinal
      cord, which relay signals from the hypothalamus to the liver via the autonomic
      nervous system. The neuroendocrine and neuronal outputs of the hypothalamus are
      not separate entities. They appear to act as a single integrated regulatory
      system, far more subtle, and complex than when each is viewed in isolation.
      Consequently, hypothalamic regulation should be viewed as a summation of both
      neuroendocrine and neural influences. As a result, our endocrine-based
      understanding of diseases such as diabetes and obesity should be expanded by
      integration of neural inputs into our concept of the pathophysiological process.

PMID- 25589268
TI  - Trans-system mechanisms against ischemic myocardial injury.
AB  - A mammalian organism possesses a hierarchy of naturally evolved protective
      mechanisms against ischemic myocardial injury at the molecular, cellular, and
      organ levels. These mechanisms comprise regional protective processes, including
      upregulation and secretion of paracrine cell-survival factors, inflammation,
      angiogenesis, fibrosis, and resident stem cell-based cardiomyocyte regeneration.
      There are also interactive protective processes between the injured heart,
      circulation, and selected remote organs, defined as trans-system protective
      mechanisms, including upregulation and secretion of endocrine cell-survival
      factors from the liver and adipose tissue as well as mobilization of bone marrow,
      splenic, and hepatic cells to the injury site to mediate myocardial protection
      and repair. The injured heart and activated remote organs exploit molecular and
      cellular processes, including signal transduction, gene expression, cell
      proliferation, differentiation, migration, mobilization, and/or extracellular
      matrix production, to establish protective mechanisms. Both regional and trans
      system cardioprotective mechanisms are mediated by paracrine and endocrine
      messengers and act in coordination and synergy to maximize the protective effect,
      minimize myocardial infarction, and improve myocardial function, ensuring the
      survival and timely repair of the injured heart. The concept of the trans-system
      protective mechanisms may be generalized to other organ systems-injury in one
      organ may initiate regional as well as trans-system protective responses, thereby
      minimizing injury and ensuring the survival of the entire organism. Selected
      trans-system processes may serve as core protective mechanisms that can be
      exploited by selected organs in injury. These naturally evolved protective
      mechanisms are the foundation for developing protective strategies for myocardial
      infarction and injury-induced disorders in other organ systems.

PMID- 25589270
TI  - Hypothalamus as an endocrine organ.
AB  - The endocrine hypothalamus constitutes those cells which project to the median
      eminence and secrete neurohormones into the hypophysial portal blood to act on
      cells of the anterior pituitary gland. The entire endocrine system is controlled
      by these peptides. In turn, the hypothalamic neuroendocrine cells are regulated
      by feedback signals from the endocrine glands and other circulating factors. The
      neuroendocrine cells are found in specific regions of the hypothalamus and are
      regulated by afferents from higher brain centers. Integrated function is clearly
      complex and the networks between and amongst the neuroendocrine cells allows fine
      control to achieve homeostasis. The entry of hormones and other factors into the
      brain, either via the cerebrospinal fluid or through fenestrated capillaries (in
      the basal hypothalamus) is important because it influences the extent to which
      feedback regulation may be imposed. Recent evidence of the passage of factors
      from the pars tuberalis and the median eminence casts a new layer in our
      understanding of neuroendocrine regulation. The function of neuroendocrine cells
      and the means by which pulsatile secretion is achieved is best understood for the
      close relationship between gonadotropin releasing hormone and luteinizing
      hormone, which is reviewed in detail. The secretion of other neurohormones is
      less rigid, so the relationship between hypothalamic secretion and the relevant
      pituitary hormones is more complex.

PMID- 25589271
TI  - Neuroendocrine regulation of lactation and milk production.
AB  - Prolactin (PRL) released from lactotrophs of the anterior pituitary gland in
      response to the suckling by the offspring is the major hormonal signal
      responsible for stimulation of milk synthesis in the mammary glands. PRL
      secretion is under chronic inhibition exerted by dopamine (DA), which is released
      from neurons of the arcuate nucleus of the hypothalamus into the hypophyseal
      portal vasculature. Suckling by the young activates ascending systems that
      decrease the release of DA from this system, resulting in enhanced responsiveness
      to one or more PRL-releasing hormones, such as thyrotropin-releasing hormone. The
      neuropeptide oxytocin (OT), synthesized in magnocellular neurons of the
      hypothalamic supraoptic, paraventricular, and several accessory nuclei, is
      responsible for contracting the myoepithelial cells of the mammary gland to
      produce milk ejection. Electrophysiological recordings demonstrate that shortly
      before each milk ejection, the entire neurosecretory OT population fires a
      synchronized burst of action potentials (the milk ejection burst), resulting in
      release of OT from nerve terminals in the neurohypophysis. Both of these
      neuroendocrine systems undergo alterations in late gestation that prepare them
      for the secretory demands of lactation, and that reduce their responsiveness to
      stimuli other than suckling, especially physical stressors. The demands of milk
      synthesis and release produce a condition of negative energy balance in the
      suckled mother, and, in laboratory rodents, are accompanied by a dramatic
      hyperphagia. The reduction in secretion of the adipocyte hormone, leptin, a
      hallmark of negative energy balance, may be an important endocrine signal to
      hypothalamic systems that integrate lactation-associated food intake with
      neuroendocrine systems.

PMID- 25589266
TI  - Sympathoneural and adrenomedullary responses to mental stress.
AB  - This concept-based review provides historical perspectives and updates about
      sympathetic noradrenergic and sympathetic adrenergic responses to mental stress.
      The topic of this review has incited perennial debate, because of disagreements
      over definitions, controversial inferences, and limited availability of relevant
      measurement tools. The discussion begins appropriately with Cannon's
      "homeostasis" and his pioneering work in the area. This is followed by mental
      stress as a scientific idea and the relatively new notions of allostasis and
      allostatic load. Experimental models of mental stress in rodents and humans are
      discussed, with particular attention to ethical constraints in humans. Sections
      follow on sympathoneural responses to mental stress, reactivity of catecholamine
      systems, clinical pathophysiologic states, and the cardiovascular reactivity
      hypothesis. Future advancement of the field will require integrative approaches
      and coordinated efforts between physiologists and psychologists on this
      interdisciplinary topic.

PMID- 25589272
TI  - Adrenocortical growth and cancer.
AB  - The adrenal gland consists of two distinct parts, the cortex and the medulla.
      Molecular mechanisms controlling differentiation and growth of the adrenal gland
      have been studied in detail using mouse models. Knowledge also came from
      investigations of genetic disorders altering adrenal development and/or function.
      During embryonic development, the adrenal cortex acquires a structural and
      functional zonation in which the adrenal cortex is divided into three different
      steroidogenic zones. Significant progress has been made in understanding adrenal
      zonation. Recent lineage tracing experiments have accumulated evidence for a
      centripetal differentiation of adrenocortical cells from the subcapsular area to
      the inner part of the adrenal cortex. Understanding of the mechanism of
      adrenocortical cancer (ACC) development was stimulated by knowledge of adrenal
      gland development. ACC is a rare cancer with a very poor overall prognosis.
      Abnormal activation of the Wnt/beta-catenin as well as the IGF2 signaling plays
      an important role in ACC development. Studies examining rare genetic syndromes
      responsible for familial ACT have played an important role in identifying genetic
      alterations in these tumors (like TP53 or CTNNB1 mutations as well as IGF2
      overexpression). Recently, genomic analyses of ACT have shown gene expression
      profiles associated with malignancy as well as chromosomal and methylation
      alterations in ACT and exome sequencing allowed to describe the mutational
      landscape of these tumors. This progress leads to a new classification of these
      tumors, opening new perspectives for the diagnosis and prognostication of ACT.
      This review summarizes current knowledge of adrenocortical development, growth,
      and tumorigenesis.

PMID- 25589269
TI  - Neural control of the circulation: how sex and age differences interact in
      humans.
AB  - The autonomic nervous system is a key regulator of the cardiovascular system. In
      this review, we focus on how sex and aging influence autonomic regulation of
      blood pressure in humans in an effort to understand general issues related to the
      cardiovascular system as a whole. Younger women generally have lower blood
      pressure and sympathetic activity than younger men. However, both sexes show
      marked interindividual variability across age groups with significant overlap
      seen. Additionally, while men across the lifespan show a clear relationship
      between markers of whole body sympathetic activity and vascular resistance, such
      a relationship is not seen in young women. In this context, the ability of the
      sympathetic nerves to evoke vasoconstriction is lower in young women likely as a
      result of concurrent beta2-mediated vasodilation that offsets alpha-adrenergic
      vasoconstriction. These differences reflect both central sympatho-inhibitory
      effects of estrogen and also its influence on peripheral vasodilation at the
      level of the vascular smooth muscle and endothelium. By contrast postmenopausal
      women show a clear relationship between markers of whole body sympathetic traffic
      and vascular resistance, and sympathetic activity rises progressively in both
      sexes with aging. These major findings in humans are discussed in the context of
      differences in population-based trends in blood pressure and orthostatic
      intolerance. The many areas where there is little sex-specific data on how the
      autonomic nervous system participates in the regulation of the human
      cardiovascular system are highlighted.

PMID- 25589274
TI  - Developmental conditioning of the vasculature.
AB  - There is increasing evidence from epidemiological and experimental animal studies
      that the early life environment, of which nutrition is a key component, acts
      through developmental adaptive responses to set the capacity of cardiovascular
      and metabolic pathways to respond to physiological and pathophysiological
      challenges in later life. One finding that is consistent to both population
      studies and animal models is the propensity for such effects to induce
      endothelial dysfunction throughout the vascular tree, including the
      microvasculature. Obesity, type 2 diabetes and hypertension are associated with
      changes in microvascular function affecting multiple tissues and organs. These
      changes may be detected early, often before the onset of macrovascular disease
      and the development of end organ damage. Suboptimal maternal nutrition and fetal
      growth result in reduced microvascular perfusion and functional dilator capacity
      in the offspring, which together with microvascular rarefaction and remodeling
      serve to limit capillary recruitment, reduce exchange capacity and increase
      diffusion distances of metabolic substrates; they also increase local and overall
      peripheral resistance. This article explores how a developmentally conditioned
      disadvantageous microvascular phenotype may represent an important and additional
      risk factor for increased susceptibility to the development of cardio-metabolic
      disease in adult life and considers the cell signaling pathways associated with
      microvascular dysfunction that may be "primed" by the maternal environment. As
      the microvasculature has been shown to be a potential target for early
      therapeutic and lifestyle intervention, this article also considers evidence for
      the efficacy of such strategies in humans and in animal models of the
      developmental origins of health and disease.

PMID- 25589276
TI  - [Reference standards in diagnostic research: problems and solutions].
AB  - The accuracy of diagnostic tests is of utmost importance as biased test results
      may lead to wrong decisions in clinical practice. In diagnostic accuracy research
      the results of a diagnostic test, model or strategy are compared to those of the
      reference standard, i.e. the best available method to determine whether a certain
      condition or disease is present or absent. Problems with the reference standard
      lead to biased test results. The umbrella term for this is 'verification bias'.
      Verification bias arises if the reference standard cannot be applied to all
      patients, if investigators use different reference standards or simply because
      there is no reference standard. Correction of these problems is often possible,
      and, if it is applied in a transparent and reproducible fashion it will deliver
      useful diagnostic information. Clinicians who use a diagnostic test should take
      possible verification bias into account.

PMID- 25589277
TI  - [Post-injection syndrome after depot injection of olanzapine].
AB  - BACKGROUND: Olanzapine pamoate injection is an anti-psychotic depot to be
      administered intramuscularly once every 2-4 weeks. A post-injection syndrome may
      occur shortly after administration, resulting in an acute intoxication with
      olanzapine. CASE DESCRIPTION: A 42-year-old patient with a schizophrenic disorder
      lost consciousness 30 min after administration of olanzapine pamoate. He was
      admitted to a nearby hospital with tachycardia, hypotension, pin-point pupils and
      respiratory distress leading to reduced oxygen saturation. He was ventilated
      during one night and recovered within 2 days. CONCLUSION: A post-injection
      syndrome may develop after administration of olanzapine pamoate when the entire
      dose olanzapine is released at once from the muscle. Therefore, the patient
      should be observed for at least 3 hours after every injection. The risk of a post
      injection syndrome and the necessary observation period should to be taken into
      account when deciding to start treatment with olanzapine pamoate depot.

PMID- 25589264
TI  - Distal convoluted tubule.
AB  - The distal convoluted tubule (DCT) is a short nephron segment, interposed between
      the macula densa and collecting duct. Even though it is short, it plays a key
      role in regulating extracellular fluid volume and electrolyte homeostasis. DCT
      cells are rich in mitochondria, and possess the highest density of Na+/K+-ATPase
      along the nephron, where it is expressed on the highly amplified basolateral
      membranes. DCT cells are largely water impermeable, and reabsorb sodium and
      chloride across the apical membrane via electroneurtral pathways. Prominent among
      this is the thiazide-sensitive sodium chloride cotransporter, target of widely
      used diuretic drugs. These cells also play a key role in magnesium reabsorption,
      which occurs predominantly, via a transient receptor potential channel (TRPM6).
      Human genetic diseases in which DCT function is perturbed have provided critical
      insights into the physiological role of the DCT, and how transport is regulated.
      These include Familial Hyperkalemic Hypertension, the salt-wasting diseases
      Gitelman syndrome and EAST syndrome, and hereditary hypomagnesemias. The DCT is
      also established as an important target for the hormones angiotensin II and
      aldosterone; it also appears to respond to sympathetic-nerve stimulation and
      changes in plasma potassium. Here, we discuss what is currently known about DCT
      physiology. Early studies that determined transport rates of ions by the DCT are
      described, as are the channels and transporters expressed along the DCT with the
      advent of molecular cloning. Regulation of expression and activity of these
      channels and transporters is also described; particular emphasis is placed on the
      contribution of genetic forms of DCT dysregulation to our understanding.

PMID- 25589278
TI  - [Loin pain haematuria syndrome].
AB  - BACKGROUND: Loin pain haematuria syndrome is characterised by episodes of loin
      pain and microscopic or macroscopic haematuria, without a urological origin. CASE
      DESCRIPTION: We describe a 39-year-old woman who was referred to us because of
      microscopic haematuria and proteinuria without an apparent cause, which had been
      present for 20 years. For 9 months she had also had continuous loin pain,
      aggravated by exertion. Additional examination showed erythrocytes in the renal
      tubules and a thin glomerular basement membrane. We made the diagnosis of "loin
      pain haematuria syndrome based on thin basement membrane nephropathy".
      CONCLUSION: Loin pain haematuria syndrome is a potentially debilitating disorder
      that is often poorly recognized due to the unfamiliarity of physicians with this
      condition. Treatment of patients with loin pain haematuria syndrome consists of
      patient education, treatment with ACE inhibitors, pain medication and cognitive
      behavioural therapy. Renal artery denervation can be considered in cases of
      persistent, disabling pain.

PMID- 25589280
TI  - [Targeted public funding for health research in the Netherlands].
AB  - The Dutch government funds health research in several ways. One component of
      public funding consists of funding programmes issued by the Netherlands
      Organisation for Health Research and Development (ZonMw). The majority of ZonMw's
      programmes provide funding for research in specific health research areas. Such
      targeted funding plays an important role in addressing knowledge gaps and in
      generating products for which there is a need. Good governance of the allocation
      of targeted funding for health research requires three elements: a research
      agenda, an overview of the health research currently being conducted, and a
      transparent decision-making process regarding the distribution of funds. In this
      article, we describe how public funding for health research is organized in the
      Netherlands and how the allocation of targeted funds is governed. By describing
      the questions that the current model of governance raises, we take a first step
      towards a debate about the governance of targeted public funding for health
      research in the Netherlands. 

PMID- 25589279
TI  - [Acute hamstring injuries in athletes].
AB  - Acute hamstring injuries are the most common injuries in participants in popular
      sports such as football and track and field athletics. The diagnosis is made if
      there is a history of acute-onset pain in the posterior thigh, and presence of
      the triad of pain on contraction, stretching and palpation. Additional
      investigations and possible referral for surgical intervention are indicated if
      there is a suspicion of a complete hamstring rupture or avulsion fracture, both
      of which are rare. The basis of treatment of patients with acute hamstring
      injuries without complete rupture is a progressive physiotherapeutic exercise
      programme. Currently there is insufficient scientific evidence to support other
      treatment methods. The mean recovery time for athletes with acute hamstring
      injuries is 3-6 weeks. The individual recovery time is however hard to predict.
      It is difficult to define exactly when the sport can be resumed, particularly
      because of the high risk of recurrent hamstring injury. The most valuable
      indications for the risk of recurrent hamstring injury are: a history of previous
      injuries of the athlete; monitoring hamstring tenderness; flexibility; and
      strength of the hamstring after resuming sporting activities.

PMID- 25589281
TI  - [Chronic dizziness in older people: apply a multifactorial approach].
AB  - It has been suggested that chronic dizziness in older people may constitute a
      multifactorial geriatric syndrome. Considering dizziness to be a geriatric
      syndrome with multiple contributory factors may provide additional leads for
      treatment. A structured history, followed by physical examination and additional
      tests if necessary, can yield clues to factors that may contribute to dizziness.
      To illustrate such a multifactorial approach, we present two patients with
      chronic dizziness. In both cases, the general practitioner considered
      multifactorial dizziness with several treatable contributory factors. By treating
      these contributory factors, the frequency of dizziness and dizziness-related
      impairment decreased temporarily in one patient and permanently in the other. 

PMID- 25589282
TI  - [A woman with gingival hyperplasia].
AB  - A woman visited her dentist with complaints of swollen gums. If there was a
      serious infection of multiple teeth, the surgeon had to do a total extraction of
      the upper jaw. The clinical picture was suspicious for a lymphoma, a fibromatosis
      or a gingivitis. The biopsy showed a chronical infection. In this case the
      gingival overgrowth and the subsequent infection of the teeth were caused by
      nifedipine. Gingival enlargement can be a consequence of the administration of
      calcium channel blockers and can occur if these are administered during a few
      months or years. The incidence is 0,01-0,1% and the prevalence is 20%. Drug
      substitution should be considered a valid treatment option and can be successful
      within a few weeks.

PMID- 25589283
TI  - [Optimizing hypertension drug treatment: can the patients do it better
      themselves?].
AB  - A recent study trial shows that in high-risk patients with hypertension, blood
      pressure measurements and initiation of changes in blood pressure lowering drugs
      by the patient him- or herself reduces the systolic blood pressure by on average
      of 9 mmHg compared with usual care. Even though additional trials confirming
      these findings are useful, self-management of high-risk patients with
      hypertension could be considered in daily practice. 

PMID- 25589284
TI  - [Cognitive behavioural therapy for breast cancer: cost-effectiveness
      demonstrated].
AB  - Behavioural medicine research provides evidence for the positive effects of
      cognitive behavioural approaches to psychosocial problems in patients with cancer
      and other chronic somatic illnesses. In an extension of this research line, Mewes
      et al. now provide evidence for the cost-effectiveness of cognitive behavioural
      therapy and physical exercise for alleviating treatment-induced menopausal
      symptoms in breast cancer patients [J Cancer Surviv, Sep 2 2014]. These important
      findings are discussed and put into the context of future research and clinical
      practice regarding quality of life, quality-adjusted life years and patient
      reported outcomes. The benefits for the women concerned appear to be
      considerable. 

PMID- 25589285
TI  - [The complexity of medical care of frail older patients].
AB  - Medicine for frail elderly patients is complex because of the omnipresent
      multimorbidity, multicausality, the high risk of adverse effects, lack of an
      evidence base for guideline-based treatment options, and the predominance of
      quality of life-related outcomes, rather than mortality and morbidity. This
      complexity puts off most medical students, while there is a requirement for
      physicians who like and are well trained to work with frail older persons.
      Luckily, there are signs of increasing interest, for example in the excellent
      introduction to geriatric medicine written by author/surgeon Atul Gawande in his
      last book "Being mortal" (2014). With this commentary, this journal is starting a
      series presenting new research findings, insights and case studies on frail older
      patients in order to spread the expanding knowledge base of geriatrics, and
      suggest tools for working effectively with this fast-growing, complex but
      rewarding patient group. 

PMID- 25589286
TI  - Local and systemic metal ion release occurs intraoperatively during correction
      and instrumented spinal fusion for scoliosis.
AB  - STUDY DESIGN: Prospective pilot study. OBJECTIVES: The aim of this study was to
      measure titanium, niobium and aluminium levels in various intraoperative and
      postoperative samples to determine patterns of metal ion release that occur
      within the first month following instrumented spinal fusion. Raised serum metal
      ion levels are reported following instrumented spinal fusion in adolescent
      idiopathic scoliosis. The exact topological origin and chronology of metal ion
      release remains conjectural. Recent literature suggests an immediate rise in
      serum metal levels within the first postoperative week. METHODS: Titanium,
      niobium and aluminium levels were measured before, during and after surgery in
      serum and local intraoperative fluid samples obtained from two pediatric patients
      undergoing posterior correction and instrumentation for scoliosis. RESULTS:
      Measurable metal ion levels were detected in all local samples obtained from
      wound irrigation fluid, cell saver blood, and fluid that immersed metal universal
      reduction screw tabs. Postoperative serum metal ion levels were elevated compared
      to baseline preoperative levels. In general, metal ion levels were considerably
      higher in the intraoperative fluid samples compared to those observed in the
      serum levels. CONCLUSION: Our findings of contextually high metal ion
      concentrations in intraoperative and early postoperative samples provide further
      empirical support of a 'putting-in' phenomenon of metal ion release following
      instrumented spinal fusion. This challenges existing beliefs that metal ion
      release occurs during an intermediate 'wearing-in' phase. We recommend thorough
      irrigation of the operative site prior to wound closure to dilute and remove
      intraoperative metal ion debris. Possibilities of filtering trace metal ions from
      cell saver content may be considered.

PMID- 25589287
TI  - Splenic lipidosis in intensively cultured perch, Perca fluviatilis L.
AB  - Macroscopically visible lipid deposition varying in size from pinpoint to 8-mm
      diameter was found in spleens of a population of intensively farmed perch, Perca
      fluviatilis L. over a 24-month rearing period. Large agglomerates of adipocytes
      distinguishable from surrounding normal tissue occurred in all individuals with
      spleen lipidosis. Several affected fish presented total dystrophy of large
      clusters of hepatocytes. Prevalence of lipidosis was 5.0% at 12 months and 16.6%
      at 24 months. There was no significant difference between fatty acid profiles of
      liver or perivisceral fat of perch with and without lipidosis except for
      linoleic, myristic, gamma-linoleic, cis-eicosatrienic, palmitooleic acid. Body
      weight and hepatosomatic, perivisceral fat and splenosomatic indices were not
      associated with lipidosis. There was no significant effect of lipidosis on
      mortality or growth.

PMID- 25589288
TI  - Cardioprotective properties of citicoline against hyperthyroidism-induced
      reperfusion damage in rat hearts.
AB  - Hyperthyroidism represents an increased risk factor for cardiovascular morbidity,
      especially when the heart is subjected to an ischemia/reperfusion process. The
      aim of this study was to explore the possible protective effect of the nucleotide
      citicoline on the susceptibility of hyperthyroid rat hearts to undergo
      reperfusion-induced damage, which is associated with mitochondrial dysfunction.
      Hence, we analyzed the protective effect of citicoline on the electrical behavior
      and on the mitochondrial function in rat hearts. Hyperthyroidism was established
      after a daily i.p. injection of triiodothyronine (at 2 mg/kg of body weight)
      during 5 days. Thereafter, citicoline was administered i.p. (at 125 mg/kg of body
      weight) for 5 days. In hyperthyroid rat hearts, citicoline protected against
      reperfusion-induced ventricular arrhythmias. Moreover, citicoline maintained the
      accumulation of mitochondrial Ca(2+), allowing mitochondria to reach a high
      transmembrane electric gradient that protected against the release of cytochrome
      c. It also preserved the activity of the enzyme aconitase that inhibited the
      release of cytokines. The protection also included the inhibition of oxidative
      stress-induced mDNA disruption. We conclude that citicoline protects against the
      reperfusion damage that is found in the hyperthyroid myocardium. This effect
      might be due to its inhibitory action on the permeability transition in
      mitochondria. 

PMID- 25589289
TI  - Robustness screen in enantioselective catalysis enabled generation of
      enantioenriched heterocyclic scaffolds in one pot.
AB  - Enantioselective catalysis has emerged as a powerful synthetic paradigm and has
      accelerated the development of new methods to make diverse chiral molecules.
      Generally, these reactions are very sensitive to the steric and electronic
      environment present in the catalyst as well as the substrates. With this
      scenario, the presence of an additional component in the reaction mixture is
      expected to add complexity in achieving the enantioselective variants. Herein, we
      report that various enantioenriched molecules could be obtained from multiple
      starting materials in one pot. The reaction of aminoaromatics A with alkynols B1,
      B2, B3...?Bn with a Au(I)/chiral Bronsted acid catalyst afforded AB1*, AB2*,
      AB3*...ABn*; while, the reaction of alkynols B with aminoaromatics A1, A2,
      A3...An under the same reaction conditions gave A1B*, A2B*, A3B*...AnB*.

PMID- 25589275
TI  - Autonomic control of the eye.
AB  - The autonomic nervous system influences numerous ocular functions. It does this
      by way of parasympathetic innervation from postganglionic fibers that originate
      from neurons in the ciliary and pterygopalatine ganglia, and by way of
      sympathetic innervation from postganglionic fibers that originate from neurons in
      the superior cervical ganglion. Ciliary ganglion neurons project to the ciliary
      body and the sphincter pupillae muscle of the iris to control ocular
      accommodation and pupil constriction, respectively. Superior cervical ganglion
      neurons project to the dilator pupillae muscle of the iris to control pupil
      dilation. Ocular blood flow is controlled both via direct autonomic influences on
      the vasculature of the optic nerve, choroid, ciliary body, and iris, as well as
      via indirect influences on retinal blood flow. In mammals, this vasculature is
      innervated by vasodilatory fibers from the pterygopalatine ganglion, and by
      vasoconstrictive fibers from the superior cervical ganglion. Intraocular pressure
      is regulated primarily through the balance of aqueous humor formation and
      outflow. Autonomic regulation of ciliary body blood vessels and the ciliary
      epithelium is an important determinant of aqueous humor formation; autonomic
      regulation of the trabecular meshwork and episcleral blood vessels is an
      important determinant of aqueous humor outflow. These tissues are all innervated
      by fibers from the pterygopalatine and superior cervical ganglia. In addition to
      these classical autonomic pathways, trigeminal sensory fibers exert local,
      intrinsic influences on many of these regions of the eye, as well as on some
      neurons within the ciliary and pterygopalatine ganglia.

PMID- 25589291
TI  - Time dilates more with apparent than with physical speed.
AB  - The perceived duration of a moving stimulus correlates positively with its speed.
      It is not known whether such duration dilation depends on the physical or
      apparent speed. Here we show the latter to be true. The perceived duration of a
      shortly presented (500, 900, 1300 ms) Gabor patch whose carrier moved at 1
      degrees /s in a direction opposite to a background of random black dots rigidly
      moving at 3 degrees /s appeared to last 20% longer and to drift 240% faster than
      the same Gabor carrier moving in the same direction as the random-dot background.
      Assessment of the perceived speed of each of the two configurations relative to a
      moving Gabor patch in the absence of the moving background allowed the comparison
      of the observed duration dilation with that obtained as a function of the
      corresponding physical speeds, which should have yielded a dilation of only 7%,
      i.e., three times less. In line with the proposal that perceived duration
      correlates with the strength of the neural response evoked by the stimuli to be
      timed, the present data can be accounted for by the increased responsiveness of
      antagonistic center-surround motion-receptive fields when stimulated with center
      surround antagonist motions. 

PMID- 25589290
TI  - Broadband optical absorption by tunable Mie resonances in silicon nanocone
      arrays.
AB  - Nanostructure arrays such as nanowire, nanopillar, and nanocone arrays have been
      proposed to be promising antireflection structures for photovoltaic applications
      due to their great light trapping ability. In this paper, the optical properties
      of Si nanopillar and nanocone arrays in visible and infrared region were studied
      by both theoretical calculations and experiments. The results show that the Mie
      resonance can be continuously tuned across a wide range of wavelength by varying
      the diameter of the nanopillars. However, Si nanopillar array with uniform
      diameter exhibits only discrete resonance mode, thus can't achieve a high
      broadband absorption. On the other hand, the Mie resonance wavelength in a Si
      nanocone array can vary continuously as the diameters of the cross sections
      increase from the apex to the base. Therefore Si nanocone arrays can strongly
      interact with the incident light in the broadband spectrum and the absorbance by
      Si nanocone arrays is higher than 95% over the wavelength from 300 to 2000 nm. In
      addition to the Mie resonance, the broadband optical absorption of Si nanocone
      arrays is also affected by Wood-Rayleigh anomaly effect and metal impurities
      introduced in the fabrication process.

PMID- 25589292
TI  - How the visual aspects can be crucial in reading acquisition? The intriguing case
      of crowding and developmental dyslexia.
AB  - Developmental dyslexia (DD) is the most common neurodevelopmental disorder (about
      10% of children across cultures) characterized by severe difficulties in learning
      to read. According to the dominant view, DD is considered a phonological
      processing impairment that might be linked to a cross-modal, letter-to-speech
      sound integration deficit. However, new theories-supported by consistent data
      suggest that mild deficits in low-level visual and auditory processing can lead
      to DD. This evidence supports the probabilistic and multifactorial approach for
      DD. Among others, an interesting visual deficit that is often associated with DD
      is excessive visual crowding. Crowding is defined as difficulty in the ability to
      recognize objects when surrounded by similar items. Crowding, typically observed
      in peripheral vision, could be modulated by attentional processes. The direct
      consequence of stronger crowding on reading is the inability to recognize letters
      when they are surrounded by other letters. This problem directly translates to
      reading at a slower speed and being more prone to making errors while reading.
      Our aim is to review the literature supporting the important role of crowding in
      DD. Moreover, we are interested in proposing new possible studies in order to
      clarify whether the observed excessive crowding could be a cause rather than an
      effect of DD. Finally, we also suggest possible remediation and even prevention
      programs that could be based on reducing the crowding in children with or at risk
      for DD without involving any phonological or orthographic training. 

PMID- 25589293
TI  - James Jurin (1684-1750): a pioneer of crowding research?
AB  - James Jurin wrote an extended essay on distinct and indistinct vision in 1738. In
      it, he distinguished between "perfect," "distinct," and "indistinct vision" as
      perceptual categories, and his meticulous descriptions and analyses of perceptual
      phenomena contained observations that are akin to crowding. Remaining with the
      concepts of his day, however, he failed to recognize crowding as separate from
      spatial resolution. We present quotations from Jurin's essay and place them in
      the context of the contemporary concerns with visual resolution and crowding. 

PMID- 25589295
TI  - Reward modulates perception in binocular rivalry.
AB  - Our perception does not provide us with an exact imprint of the outside world,
      but is continuously adapted to our internal expectations, task sets, and
      behavioral goals. Although effects of reward-or value in general-on perception
      therefore seem likely, how valuation modulates perception and how such modulation
      relates to attention is largely unknown. We probed effects of reward on
      perception by using a binocular-rivalry paradigm. Distinct gratings drifting in
      opposite directions were presented to each observer's eyes. To objectify their
      subjective perceptual experience, the optokinetic nystagmus was used as measure
      of current perceptual dominance. In a first experiment, one of the percepts was
      either rewarded or attended. We found that reward and attention similarly biased
      perception. In a second experiment, observers performed an attentionally
      demanding task either on the rewarded stimulus, the other stimulus, or both. We
      found that-on top of an attentional effect on perception-at each level of
      attentional load, reward still modulated perception by increasing the dominance
      of the rewarded percept. Similarly, penalizing one percept increased dominance of
      the other at each level of attentional load. In turn, rewarding-and similarly
      nonpunishing-a percept yielded performance benefits that are typically associated
      with selective attention. In conclusion, our data show that value modulates
      perception in a similar way as the volitional deployment of attention, even
      though the relative effect of value is largely unaffected by an attention task. 

PMID- 25589294
TI  - Learning to integrate contradictory multisensory self-motion cue pairings.
AB  - Humans integrate multisensory information to reduce perceptual uncertainty when
      perceiving the world and self. Integration fails, however, if a common causality
      is not attributed to the sensory signals, as would occur in conditions of
      spatiotemporal discrepancies. In the case of passive self-motion, visual and
      vestibular cues are integrated according to statistical optimality, yet the
      extent of cue conflicts that do not compromise this optimality is currently
      underexplored. Here, we investigate whether human subjects can learn to integrate
      two arbitrary, but co-occurring, visual and vestibular cues of self-motion.
      Participants made size comparisons between two successive whole-body rotations
      using only visual, only vestibular, and both modalities together. The vestibular
      stimulus provided a yaw self-rotation cue, the visual a roll (Experiment 1) or
      pitch (Experiment 2) rotation cue. Experimentally measured thresholds in the
      bimodal condition were compared with theoretical predictions derived from the
      single-cue thresholds. Our results show that human subjects combine and optimally
      integrate vestibular and visual information, each signaling self-motion around a
      different rotation axis (yaw vs. roll and yaw vs. pitch). This finding suggests
      that the experience of two temporally co-occurring but spatially unrelated self
      motion cues leads to inferring a common cause for these two initially unrelated
      sources of information about self-motion. We discuss our results in terms of
      specific task demands, cross-modal adaptation, and spatial compatibility. The
      importance of these results for the understanding of bodily illusions is also
      discussed. 

PMID- 25589296
TI  - Area summation of first- and second-order modulations of luminance.
AB  - To extend our understanding of the early visual hierarchy, we investigated the
      long-range integration of first- and second-order signals in spatial vision. In
      our first experiment we performed a conventional area summation experiment where
      we varied the diameter of (a) luminance-modulated (LM) noise and (b) contrast
      modulated (CM) noise. Results from the LM condition replicated previous findings
      with sine-wave gratings in the absence of noise, consistent with long-range
      integration of signal contrast over space. For CM, the summation function was
      much shallower than for LM suggesting, at first glance, that the signal
      integration process was spatially less extensive than for LM. However, an
      alternative possibility was that the high spatial frequency noise carrier for the
      CM signal was attenuated by peripheral retina (or cortex), thereby impeding our
      ability to observe area summation of CM in the conventional way. To test this, we
      developed the "Swiss cheese" stimulus of Meese and Summers (2007) in which signal
      area can be varied without changing the stimulus diameter, providing some
      protection against inhomogeneity of the retinal field. Using this technique and a
      two-component subthreshold summation paradigm we found that (a) CM is spatially
      integrated over at least five stimulus cycles (possibly more), (b) spatial
      integration follows square-law signal transduction for both LM and CM and (c) the
      summing device integrates over spatially-interdigitated LM and CM signals when
      they are co-oriented, but not when cross-oriented. The spatial pooling mechanism
      that we have identified would be a good candidate component for a module involved
      in representing visual textures, including their spatial extent. 

PMID- 25589297
TI  - Contextual processing of brightness and color in Mongolian gerbils.
AB  - Brightness and color cues are essential for visually guided behavior. However,
      for rodents, little is known about how well they do use these cues. We used a
      virtual reality setup that offers a controlled environment for sensory testing to
      quantitatively investigate visually guided behavior for achromatic and chromatic
      stimuli in Mongolian gerbils (Meriones unguiculatus). In two-alternative forced
      choice tasks, animals had to select target stimuli based on relative intensity or
      color with respect to a contextual reference. Behavioral performance was
      characterized using psychometric analysis and probabilistic choice modeling. The
      analyses revealed that the gerbils learned to make decisions that required
      judging stimuli in relation to their visual context. Stimuli were successfully
      recognized down to Weber contrasts as low as 0.1. These results suggest that
      Mongolian gerbils have the perceptual capacity for brightness and color
      constancy. 

PMID- 25589298
TI  - Spatial statistics and attentional dynamics in scene viewing.
AB  - In humans and in foveated animals visual acuity is highly concentrated at the
      center of gaze, so that choosing where to look next is an important example of
      online, rapid decision-making. Computational neuroscientists have developed
      biologically-inspired models of visual attention, termed saliency maps, which
      successfully predict where people fixate on average. Using point process theory
      for spatial statistics, we show that scanpaths contain, however, important
      statistical structure, such as spatial clustering on top of distributions of gaze
      positions. Here, we develop a dynamical model of saccadic selection that
      accurately predicts the distribution of gaze positions as well as spatial
      clustering along individual scanpaths. Our model relies on activation dynamics
      via spatially-limited (foveated) access to saliency information, and, second, a
      leaky memory process controlling the re-inspection of target regions. This
      theoretical framework models a form of context-dependent decision-making, linking
      neural dynamics of attention to behavioral gaze data. 

PMID- 25589299
TI  - Context affects lightness at the level of surfaces.
AB  - Visual perception of object attributes such as surface lightness is crucial for
      successful interaction with the environment. How the visual system assigns
      lightness to image regions is not yet understood. It has been shown that the
      context in which a surface is embedded influences its perceived lightness, but
      whether that influence involves predominantly low-, mid-, or high-level visual
      mechanisms has not been resolved. To answer this question, we measured whether
      perceptual attributes of target image regions affected their perceived lightness
      when they were placed in different contexts. We varied the sharpness of the edge
      while keeping total target flux fixed. Targets with a sharp edge were consistent
      with the perceptual interpretation of a surface, and in that case, observers
      perceived significant brightening or darkening of the target. Targets with
      blurred edges rather appeared to be spotlights instead of surfaces; for targets
      with blurred edges, there was much less of a contextual effect on target
      lightness. The results indicate that the effect of context on the lightness of an
      image region is not fixed but is strongly affected by image manipulations that
      modify the perceptual attributes of the target, implying that a mid-level scene
      interpretation affects lightness perception. 

PMID- 25589300
TI  - The geometric structure of color.
AB  - Color is commonly described in terms of the three perceptual attributes-hue,
      saturation, and brightness-of which only hue has a qualitative nature, saturation
      and brightness being of a quantitative nature. A possible reason for such a
      phenomenological structure of the color manifold, and its geometric
      representation, are discussed. 

PMID- 25589301
TI  - The effect of motion on crowding: zooming text.
AB  - Crowding is the major sensory factor responsible for the slow reading speeds
      exhibited in peripheral vision. Past attempts to improve peripheral reading via
      crowding reduction have generally focused on applying spatial changes to the
      stimulus and have been largely ineffective. Recent evidence indicates that
      dynamic approaches have good potential for reducing crowding in peripheral
      reading. We tested this hypothesis by introducing "zooming" motion (smooth letter
      resizing across the presentation duration) to trigram stimuli (groups of three
      randomly selected letters) presented at 10 degrees  in the lower visual field and
      evaluating recognition of the middle letter. Crowding was alleviated in the
      presence of this motion, both when dynamic cues were introduced to all letters in
      the trigram simultaneously and when they were applied to individual letters
      alone. The magnitude and direction of crowding reduction depended on the
      amplitude and direction of motion. These results suggest that dynamic
      presentation may be a useful tool for improving peripheral reading through
      reducing letter crowding. Zooming motion, in particular, has the additional
      advantage of conserving text layout, making it a good candidate for such an
      application. 

PMID- 25589273
TI  - Neural control of the lower urinary tract.
AB  - This article summarizes anatomical, neurophysiological, pharmacological, and
      brain imaging studies in humans and animals that have provided insights into the
      neural circuitry and neurotransmitter mechanisms controlling the lower urinary
      tract. The functions of the lower urinary tract to store and periodically
      eliminate urine are regulated by a complex neural control system in the brain,
      spinal cord, and peripheral autonomic ganglia that coordinates the activity of
      smooth and striated muscles of the bladder and urethral outlet. The neural
      control of micturition is organized as a hierarchical system in which spinal
      storage mechanisms are in turn regulated by circuitry in the rostral brain stem
      that initiates reflex voiding. Input from the forebrain triggers voluntary
      voiding by modulating the brain stem circuitry. Many neural circuits controlling
      the lower urinary tract exhibit switch-like patterns of activity that turn on and
      off in an all-or-none manner. The major component of the micturition switching
      circuit is a spinobulbospinal parasympathetic reflex pathway that has essential
      connections in the periaqueductal gray and pontine micturition center. A computer
      model of this circuit that mimics the switching functions of the bladder and
      urethra at the onset of micturition is described. Micturition occurs
      involuntarily in infants and young children until the age of 3 to 5 years, after
      which it is regulated voluntarily. Diseases or injuries of the nervous system in
      adults can cause the re-emergence of involuntary micturition, leading to urinary
      incontinence. Neuroplasticity underlying these developmental and pathological
      changes in voiding function is discussed.

PMID- 25589302
TI  - Adrenal Insufficiency as a Result of Ritonavir and Exogenous Steroid Exposure:
      Report of 6 Cases and Recommendation for Management.
AB  - Numerous cases of Cushing syndrome have been reported as a result of the
      interaction between ritonavir (RTV) and exogenous steroid medications. Another
      complication that frequently occurs is secondary adrenal insufficiency, which can
      be profound and has not been well described. Here, we report 6 cases of adrenal
      suppression caused by RTV and exogenous steroids, all of which required
      corticosteroid replacement therapy and 2 of which were severe enough to require
      hospitalization. These cases add to the body of literature on the dangerous
      interaction between RTV and corticosteroids and highlight the risk of secondary
      adrenal suppression. We also review the literature on this complication and make
      a recommendation for managing and monitoring such cases. 

PMID- 25589303
TI  - Perception of HIV Testing and Counseling among Integrated Counseling and Testing
      Center Clients of Tertiary Level Hospitals.
AB  - BACKGROUND: The purpose of establishing integrated counseling and testing center
      (ICTC) is to detect HIV at the earliest time, providing information on modes of
      transmission and prevention of HIV by promoting behavioral change and reducing
      vulnerability, and informing individuals on HIV prevention, care, and treatment
      services. OBJECTIVE: To know the awareness of the clients about ICTC before
      pretest counseling. METHODS: This facility-based cross-sectional study was
      conducted among 105 pretest counseling clients who visited ICTC for the first
      time in 3 ICTCs of tertiary care hospitals attached to a medical college in
      Mangalore. RESULT: Majority of the clients were pregnant women (n = 57, 54.30%),
      and most of the clients were referred by the treating doctor (n = 91, 86.7%).
      Most of the clients, being unaware of ICTC, are not aware of its functions and
      activities. CONCLUSION: Although ICTCs have been functional for nearly a decade,
      the awareness of ICTC and its functions among the people is poor.

PMID- 25589304
TI  - Factors Associated with Late Engagement to HIV Care in Western Kenya: A Cross
      Sectional Study.
AB  - BACKGROUND: Late presentation of patients contributes significantly to the high
      mortality reported in HIV -care and treatment programs in sub-Saharan Africa.
      METHODS: A cross-sectional study was conducted to assess factors associated with
      late engagement to HIV care at the Academic Model Providing Access to Healthcare
      in western Kenya. Late engagement was defined as baseline CD4 <=100 cells/mm3.
      RESULTS: Of the 10 533 participants included in the analysis, 67% were female and
      mean age was 36.7 years. Overall, 23% of the participants presented late. Factors
      associated with late engagement included male gender (adjusted odds ratio [AOR]:
      1.54, 95% confidence interval [CI]: 1.35-1.75), older age (AOR: 1.62, 95% CI:
      1.02-2.56), and longer travel time to clinic (AOR: 1.18, 95% CI: 1.04-1.34).
      CONCLUSION: Nearly one-quarter of HIV-infected patients in our setting present
      with advanced immune suppression at initial encounter. Being male, older age, and
      living further away from clinic are associated with late engagement to care.

PMID- 25589305
TI  - His-bundle bigeminy evidenced by short his-ventricular interval.

PMID- 25589307
TI  - A new FRET ratiometric fluorescent chemosensor for Hg2+ and its application in
      living EC 109 cells.
AB  - On the basis of fluorescent resonance energy transfer, a new fluorophore dyad (L)
      bearing rhodamine B and naphthalimide was developed as fluorescent ratiometric
      chemosensor for Hg(2+) in aqueous solution. L exhibited high selectivity and
      excellent sensitivity towards Hg(2+) with a broad pH span (1.0-8.0) and the
      detection limit of L was 2.11*10(-8) M. Sensor L for the detection of Hg(2+) was
      rapid and the recognizing event could complete in 2.5 min. A significant change
      in the color could be used for naked-eye detection. The selective fluorescence
      response of L to Hg(2+) is due to the Hg(2+)-promoted ring opening of spirolactam
      of rhodamine moiety, leading to a cyclization reaction of thiourea moiety. In
      addition, fluorescence imaging experiments of Hg(2+) in living EC 109 cells
      demonstrated its value of practical applications in biological systems.

PMID- 25589306
TI  - Effect of ischemic postconditioning on myocardial salvage in patients undergoing
      primary percutaneous coronary intervention for ST-segment elevation myocardial
      infarction: cardiac magnetic resonance substudy of the POST randomized trial.
AB  - In the effects of postconditioning on myocardial reperfusion in patients with ST
      segment elevation myocardial infarction (POST) trial, ischemic postconditioning
      did not improve myocardial reperfusion in 700 patients with STEMI undergoing
      primary PCI. However, the impact of postconditioning on myocardial salvage and
      infarct size still needs to be addressed. The aim of this study was to
      investigate the effect of ischemic postconditioning on myocardial salvage using
      cardiac magnetic resonance (CMR) in patients with STEMI undergoing primary PCI.
      For the CMR substudy, a total of 111 patients was analyzed, 56 in the
      postconditioning group and 55 undergoing conventional primary PCI in the control
      group. Postconditioning was performed immediately after restoration of coronary
      flow by four cycles of 1-min balloon occlusion separated by 1 min of deflation.
      The primary end point was myocardial salvage measured by CMR 3 days after the
      index event. The myocardial salvage index was not improved by ischemic
      postconditioning compared with conventional PCI (46.3 +/- 18.5 vs. 45.7 +/-
      20.5%, p = 0.86). The infarct size was not significantly different between the
      two groups (18.8 +/- 10.3 vs. 20.2 +/- 11.0%, p = 0.52). Moreover, there was no
      significant difference in the rates of microvascular obstruction or hemorrhagic
      infarction between the groups. CMR study demonstrated that ischemic
      postconditioning during primary PCI in STEMI patients did not improve myocardial
      salvage or reduce infarct size. These findings further support the results of the
      POST trial which showed no benefit of ischemic postconditioning as an adjunctive
      treatment of primary PCI.

PMID- 25589308
TI  - Clinical validation of free breathing respiratory triggered retrospectively
      cardiac gated cine balanced steady-state free precession cardiovascular magnetic
      resonance in sedated children.
AB  - BACKGROUND: Cine balanced steady-state free precession (SSFP), the preferred
      sequence for ventricular function, demands uninterrupted radio frequency (RF)
      excitation to maintain the steady-state during suspended respiration. This is
      difficult to accomplish in sedated children. In this work, we validate a
      respiratory triggered (RT) SSFP sequence that drives the magnetization to steady
      state before commencing retrospectively cardiac gated cine acquisition in a
      sedated pediatric population. METHODS: This prospective study was performed on 20
      sedated children with congenital heart disease (8.6 +/- 4 yrs). Identical imaging
      parameters were used for multiple number of signal averages (MN) and RT cine SSFP
      sequences covering both the ventricles in short-axis (SA) orientation. Image
      quality assessment and quantitative volumetric analysis was performed on the
      datasets by two blinded observers. One-sided Wilcoxon signed rank test and Box
      plot analysis were performed to compare the clinical scores. Bland-Altman (BA)
      analysis was performed on LV and RV volumes. RESULTS: Scan duration for SA stack
      using RT-SSFP (3.9 +/- 0.8 min) was slightly shorter than MN-SSFP (4.6 +/- 0.9
      min) acquisitions. The endocardial edge definition was significantly better for
      RT than MN, blood to myocardial contrast was better for RT than MN without
      reaching statistical significance, and inter slice alignment was comparable. BA
      analysis indicates that the variability of volumetric indices between RT and MN
      is comparable to inter and intra-observer variability reported in the literature.
      CONCLUSIONS: The free breathing RT-SSFP sequence allows diagnostic images in
      sedated children with significantly better edge definition when compared to MN
      SSFP, without any penalty for total scan time.

PMID- 25589309
TI  - Pediatric Patient and Hospital Characteristics Associated With Treatment of
      Peritonsillar Abscess and Peritonsillar Cellulitis.
AB  - OBJECTIVE: To identify patient and hospital characteristics associated with the
      choice of treatment for pediatric patients who present in the acute setting with
      peritonsillar abscess/cellulitis (PTA/PTC). STUDY DESIGN: A retrospective cohort
      study was performed using Healthcare Cost and Utilization Project emergency
      department, ambulatory, and inpatient state databases for the years 2010 and
      2011. Children aged 0 to 17 years were identified using International
      Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
      diagnosis code for PTA/PTC. The main outcome of interest was treatment received,
      which included medical therapy alone, incision and drainage (IND) or
      tonsillectomy. Multiple logistic regression analyses were conducted to model non
      clinical factors associated with treatment received after adjusting for age,
      hospital state, race, primary expected payer, existing chronic condition(s), and
      type of hospital. RESULTS: We identified 2994 patients who presented with
      PTA/PTC. The most common treatment choice was medical therapy alone (30.8%),
      followed by IND (30.5%) and tonsillectomy (9.4%). There were significant
      associations between treatment choice and race, primary payer status, and type of
      hospital (P < .05). We found that Hispanic patients, those with Medicaid as their
      primary expected payer, and those treated at a designated children's hospital
      were 3 nonclinical factors independently associated with an increase in
      likelihood of receiving tonsillectomy as treatment. CONCLUSION: There are
      important nonclinical factors associated with treatment of children who present
      in the acute setting with PTA/PTC. Additional research is recommended to
      understand these observed differences in care and how they may affect health
      outcomes.

PMID- 25589310
TI  - Phentermine plus topiramate for weight reduction: more tolerable and effective?

PMID- 25589311
TI  - [Simulation technologies in anesthesiology, resuscitation and intensive care:
      state of the problem].
AB  - The foundation of simulation technologies application in educational process is
      presented in the article. It is described difficulties during anesthesiologists
      resuscitators training and education of physicians of not intensive care
      specialty in intensive care methods. It was emphasized that new innovative
      educational stage is formed at present time. It is simulation stage between
      preclinical and clinical stages. Theoretical foundation and practical evidence of
      efficiency of simulation training are expressed in detail. 

PMID- 25589312
TI  - [The results of carotid endarterectomy in patients with carotid arteries stenosis
      and chronic ischemic optical neuropathy].
AB  - It was estimated an efficiency of surgical and conservative treatment of patients
      with atherosclerotic carotid arteries stenosis and chronic ischemic optical
      neuropathy. The first group included 30 patients after carotid endarterectomy.
      The second group included 20 patients who underwent conservative treatment. The
      methods of investigation included determination of visual acuity,
      autorefractometry, direct and inverse ophthalmoscopy under mydriasis, computer
      static perimetry, assessment of functional status of optic nerve by using of
      threshold of electric sensitivity and lability, ultrasonic scanning of eyes
      arteries and carotid arteries. Follow-up terms were baseline, in one month and in
      one year after surgery or conservative treatment. Improvement of visual acuity on
      0.1 and more in 1st/2nd groups was 9/2 (p=0.1629), in one year - 12/1 (p=0.0075).
      Improvement of field of vision: in 1 month in 1st/2nd groups it was 12/3
      (p=0.0692), in 1 year - 17/1 (p=0.0002). The dynamics of neurological status:
      there was equal ratio of asymptomatic/symptomatic patients at baseline in
      subgroups. In the 1st group it was 19/11 vs. 16/4 in the 2nd group (p=0.3451). In
      1 year after two kinds of treatment significant changes were revealed. There was
      26/4 in the 1st group vs. 13/7 in the 2nd group (p=0.0902) with improvement only
      after carotid endarterectomy - 19/11 at baseline vs. 26/4 in 1 year (p=0.0716).
      Insignificant deterioration was diagnosed after conservative treatment - 16/4 vs.
      13/7 (p=0.4801). 

PMID- 25589313
TI  - [Caprini score as individual risk assessment model of postoperative venous
      thromboembolism in patients with high surgical risk].
AB  - The aim of this study was to estimate the role of Caprini model in forecasting of
      postoperative venous thromboembolism (VTE) in patients with high surgical risk
      and to determine patients with extremely high risk of venous thrombosis by using
      of this scale. It was performed prospective multicenter observational study
      involving 140 high risk patients who underwent large abdominal (48%) or
      neurosurgical (52%) intervention. All patients were assessed with the Caprini
      model and had a mean score of 9.5+/-2.7 (range: 5-15). Complex postoperative
      prevention of venous thromboembolic complications included elastic compression of
      low extremities and standard prophylactic doses of direct anticoagulants. Duplex
      ultrasonic scanning was performed during the first 12 hours after surgery and
      then every 3-5 days until discharge to assess the lower limbs venous system. If
      venous thrombosis was observed pulmonary embolism has been excluded by using of
      echocardiography, planar perfusion scintigraphy of the lungs, SPECT-imaging with
      computed tomography. Venous thrombosis was diagnosed in 39 (28%) patients. The
      incidence of VTE was 1.9% in the lowest tertile of the Caprini score (5-8); it
      was 26.1% in the middle tertile (score 9-11) and 65% in the upper tertile (score
      12-15) (p<0.001). The area under ROC curve was 0.874 (95% CI 0.81 to 0.94) and
      Caprini score 11 was a cut-off point that provided the highest sensitivity and
      specificity. 2 (2.6%) of 77 patients with score less than 11 had venous
      thrombosis. In contrast, 37 (58.7%) of 63 patients with Caprini score 11 and more
      had venous thrombosis (p<0.001). There is significant correlation between Caprini
      scores and frequency of postoperative venous thromboembolism in patients with
      high surgical risk. Score 11 and more can identify patients with extremely high
      risk. These patients need for more effective prevention. 

PMID- 25589314
TI  - [Experience of two-staged liver resection (ALPPS)].
AB  - The aim was to estimate single center results of ALPPS. It was performed 5 ALPPS
      procedures in our center during the period from February 2013 to March 2014.
      There were 1 female and 4 males in the age of 58-64 years. The indications for
      surgery were colorectal cancer metastases in 4 cases, bladder cancer metastases
      in 1 observation. The operations included 3 right-sided hemihepatectomies, 2
      extended right-sided hemihepatectomies. In 3 cases operations were accompanied by
      additional atypical resection of residuary liver lobe. In 2 observations
      unsuccessful embolization of the portal vein was done. The waiting time between
      procedures consisted 18 days in the first case and 6 days in other cases. Final
      hepatectomy was performed in all observations. Hypertrophy of left liver lobe was
      more than 50% in all cases. Postoperative complications happened in 3 out of 5
      cases. One patient died because of progressive thrombosis of inferior vena cava
      and developed multiorgan failure. There were 1 complication of level 2 and 1
      complication of level 4a according to Dindo-Clavien classification. One patient
      had biliary fistula after final hepatectomy. It wasn't observed cases of severe
      liver failure. ALPPS is appropriate method for fast residuary liver lobe
      hypertrophy. It allows to perform R0-resection of liver but ALPPS has high
      postoperative complication rate. 

PMID- 25589315
TI  - [Esophageal stenting complications].
AB  - The aim of the study was to analyze esophageal stenting complications in case of
      cancer and benign diseases. It was investigated complications in 8 patients in
      terms from 7 days to 1 year after intervention. In 4 patients esophageal stenting
      was performed for constrictive esophageal cancer and compression with pulmonary
      cancer metastases into mediastinal lymphatic nodes. 2 patients had esophageal
      stenting for post-tracheostomy tracheo-esophageal fistula, 1 patient - for
      spontaneous esophageal rupture, 1 patient - for post-burn scar narrowing of
      esophagus and output part of the stomach. Severe patients' condition with tumor
      was determined by intensive esophageal bleeding in 2 cases, bilateral abscessed
      aspiration pneumonia, tumor bleeding, blood aspiration (1 case), posterior
      mediastinitis (1 case). Severe patients' condition with benign disease was
      associated with decompensated esophageal narrowing about proximal part of stent
      (1 case), increase of tracheo-esophageal fistula size complicated by aspiration
      pneumonia (1 case), stent migration into stomach with recurrence of esophago
      mediastino-pleural fistula and pleural empyema (1 case), decompensated narrowing
      of esophagus and output part of the stomach (1 case). Patients with cancer died.
      And patients with benign diseases underwent multi-stage surgical treatment and
      recovered. Stenting is palliative method for patients with esophageal cancer.
      Patients after stenting should be under outpatient observation for early
      diagnosis of possible complications. Esophageal stenting in patients with benign
      diseases should be performed only by life-saving indications, in case of
      inability of other treatment and for the minimum necessary period. 

PMID- 25589316
TI  - [Rationale of application of the drug Cytoflavin in complex treatment of patients
      with diabetic foot syndrome with mediacalcification arteries].
AB  - The study involved 60 patients with diabetic foot syndrome (DFS) with severe
      subcompensated diabetes type II. All patients were available mediacalcification
      foot and lower leg arteries of different severity. Depending on the treatment,
      all patients were divided into 2 groups by stratified randomization. The first
      group received basic therapy that is indicated for DFS which included
      antibiotics, vessels extending drugs neuroprotective and detoxification
      facilities. The second group of patients in addition to basic therapy received
      the drug cytoflavin 10 ml 0.9% NaCl 200 ml for 10 days, followed by transfer to
      the tablet form cytoflavin 2 tablets 2 times a day orally for 1 month. We noted a
      positive trend treat patients in addition to standard therapy received the drug
      cytoflavin, resulting in a marked neuroprotective, antihypoxant and antioxidant
      effects of the drug. Thus, the use of complex surgical treatment of patients with
      mixed form DFS cytoflavin reduces the severity of distal polyneuropathy, improves
      tissue oxygenation and restores the activity of antioxidant enzymes system,
      manifested a marked neuroprotective, anti-hypoxic and antioxidant effects of
      drugs and indications to justify its use in this condition. 

PMID- 25589317
TI  - [Blood loss during total knee-joint replacement: a combination of anticoagulant
      and hemostatic techniques].

PMID- 25589318
TI  - [Minimally-invasive treatment of upper urinary tract strictures].

PMID- 25589319
TI  - [Removal of the posterior mediastinum chordoma with resection of aortic arch and
      descending aorta, thoracic esophagus and the upper lobe of the left lung under
      left atrial-aortic bypass].

PMID- 25589320
TI  - [Postoperative small intestine intussusception in adults].

PMID- 25589321
TI  - [Pancreatogenic ascites in chronic pancreatitis].

PMID- 25589322
TI  - [Duodenal bleeding from heterotopic salivary gland].

PMID- 25589323
TI  - [Intramuscular myxoma of iliopsoas muscle].

PMID- 25589324
TI  - [Surgical treatment of patient with paraprosthetic infection complicated by
      prosthetic-enteric bedsores and multiple abscesses of the right kidney after
      aorto-femoral reconstruction and renal artery replacement].

PMID- 25589325
TI  - [Traumatic rupture of giant multinodular goiter with mixed etiology].

PMID- 25589327
TI  - Evidence to implementation continuum for universal health coverage.

PMID- 25589326
TI  - Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole,
      albendazole plus oxantel pamoate, and mebendazole alone against Trichuris
      trichiura and concomitant soil-transmitted helminth infections: a four-arm,
      randomised controlled trial.
AB  - BACKGROUND: Existing anthelmintic drugs (eg, albendazole and mebendazole) have
      low efficacy against the intestinal nematode species Trichuris trichiura and the
      drug pipeline is exhausted. We aimed to investigate the strategy of combination
      chemotherapy with existing drugs to establish whether their efficacy could be
      enhanced and broadened. METHODS: In this randomised controlled trial, we compared
      three drug combinations and one standard drug alone in children aged 6-14 years
      in two schools on Pemba Island, Tanzania infected with T trichiura and
      concomitant intestinal nematodes. We assigned children, via a randomisation list
      with block sizes of either four or eight, to orally receive albendazole (400 mg)
      plus ivermectin (200 MUg/kg); albendazole (400 mg) plus mebendazole (500 mg);
      albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or mebendazole (500 mg)
      alone. The primary endpoints were the proportion of children cured of T trichiura
      infection and the reduction of T trichiura eggs in stool based on geometric
      means, both analysed by available case. This study is registered with ISRCTN,
      number ISRCTN80245406. FINDINGS: We randomly assigned 440 eligible children
      infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four
      treatment groups (110 children per group). Data for 431 children were included in
      the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of
      108 children cured [68.5%, 95% CI 59.6-77.4]; egg reduction 99.2%, 98.7-99.6) and
      albendazole plus ivermectin (30 of 109 cured [27.5%, 19.0-36.0]; egg reduction
      94.5%, 91.7-96.3) were significantly more effective against T trichiura than
      mebendazole alone (nine of 107 cured [8.4%, 3.1-13.8]; egg reduction 58.5%, 45.2
      70.9). Albendazole plus mebendazole had similar low efficacy (nine of 107 cured
      [8.4%, 3.1-13.8; egg reduction 51.6%, 35.0-65.3) to mebendazole alone. About a
      fifth of the children reported adverse events, which were mainly mild. Abdominal
      cramps and headache were the most common adverse events after treatment;
      abdominal cramps were reported by 13 (12.0%) children for albendazole plus
      ivermectin, 10 (9.3%) for albendazole plus mebendazole, 20 (18.2%) for
      albendazole plus oxantel pamoate, and 16 (14.5%) for mebendazole; headaches were
      reported by 5 (4.6%) children for albendazole plus ivermectin, 6 (5.6%) for
      albendazole plus mebendazole, 12 (10.9%) for albendazole plus oxantel pamoate,
      and 7 (6.4%) for mebendazole. INTERPRETATION: Our head-to-head comparison of
      three combination chemotherapies showed the highest efficacy for albendazole plus
      oxantel pamoate for the treatment of infection with T trichiura. Further studies
      should investigate the combination of albendazole plus oxantel pamoate so that it
      can be considered for soil-transmitted helminthiasis control programmes. FUNDING:
      Medicor Foundation and Swiss National Science Foundation.

PMID- 25589328
TI  - Going forward through the world: thinking theoretically about first person
      perspective digital ethnography.
AB  - Engaging first person perspective recording as a type of digital ethnography
      invites the question of how we might understand the status of the knowledge it
      produces. To examine this question I will focus on how first person perspective
      camera recordings might be engaged and made analytically meaningful in
      disciplines where naturalistic and observational visual recording is uncommon and
      where the idea of producing naturalistic or optimally objective visual recordings
      of people's lives is problematized. In doing so I explore the wider possibilities
      of these technologies for ethnographic research both beyond their existing uses
      and for interdisciplinary research where the images they produce might be
      analysed from more than one perspective. 

PMID- 25589329
TI  - Corrigenda: Two new species of Mediomastus (Annelida, Capitellidae) from Tokyo
      Bay, Japan. ZooKeys 422: 115-126.
AB  - [This corrects the article DOI: 10.3897/zookeys.422.7501.]. 

PMID- 25589331
TI  - Association of tumour necrosis factor-alpha polymorphism in patients with end
      stage renal disease.
AB  - AIM: Cytokines play a critical role in the pathophysiology of end stage renal
      disease (ESRD). Tumour necrosis factor-a (TNF-alpha) is an important cytokine
      involved in initiation and progression of renal diseases. The present study
      evaluated the association of specific alleles/genotype of TNF-alpha with chronic
      renal failure (CRF) and ESRD. METHODS: A total of 30 CRF patients who were not on
      renal replacement therapy, 85 ESRD patients and 120 healthy controls were
      included in the study. The ESRD patients belonged to two subgroups: patients on
      peritoneal dialysis (PD) without peritonitis (n = 50) and with peritonitis (n =
      35). TNF-alpha genotype (-308 G > A) was determined by polymerase chain reaction
      restriction fragment length polymorphism. Level of TNF-alpha was detected in the
      sera of patients and healthy controls by enzyme linked immunosorbent assay
      (ELISA), and also in the dialysate of patients on PD. RESULTS: The genotypic
      distributions of TNF-alpha (-308 G > A) were significantly different between
      patients and controls. Homozygous A/A genotype had significant association with
      CRF and ESRD (P < 0.001, odds ratio [OR] = 25.02). Frequency of homozygous A/A
      genotype was significantly higher in all subgroups of patients than controls (CRF
      40% vs control 2.5%, P = 0.001; PD 54% vs control 2.5%, P < 0.001 and PD with
      peritonitis 62.8% vs control 2.5%, P < 0.001). Patients with homozygous A/A
      genotype had significantly elevated levels of TNF-alpha in the sera of patients
      and in the dialysate of PD patients. CONCLUSIONS: Individuals with homozygous TNF
      alpha (-308 G > A) polymorphisms has significant association with CRF and ESRD,
      and thus may be a predictor for development of the disease. Elevated TNF-alpha
      may be a contributory factor.

PMID- 25589330
TI  - E-health physical activity interventions and moderate-to-vigorous intensity
      physical activity levels among working-age women: a systematic review protocol.
AB  - BACKGROUND: The rapid pace of modern life requires working-age women to juggle
      occupational, family, and social demands. Despite the large numbers of working
      age women in developed countries and the proven benefits of regular moderate-to
      vigorous intensity aerobic physical activity (MVPA) in chronic disease
      prevention, few women meet current physical activity (PA) recommendations of 150
      min of MVPA per week. It is important that appropriate and effective behavioral
      interventions targeting PA are identified and developed to improve the MVPA
      levels of working-age women. As women worldwide embrace modern technologies, e
      health innovations may provide opportune and convenient methods of implementing
      programs and strategies to target PA in an effort to improve MVPA levels and
      cardiometabolic health. Previous reviews on this topic have been limited; none
      have focused on working-age women from developed countries who exhibit
      inappropriately low PA levels. It remains unknown as to which e-health
      interventions are most effective at increasing MVPA levels in this population.
      The purpose of this systematic review is to examine the effectiveness of e-health
      interventions in raising MVPA levels among working-age women in developed
      countries and to examine the effectiveness of these interventions in improving
      the health of women. METHODS: Eight electronic databases will be searched to
      identify all prospective cohort and experimental studies examining the impact of
      e-health interventions for increasing MVPA levels among working-age women (mean
      age 18-65 years) in developed countries. Gray literature including theses,
      dissertations, and government reports will also be examined. Study quality will
      be assessed using a modified Downs and Black checklist, and risk of bias will be
      assessed within and across all included studies using the Cochrane's risk of bias
      tool and Grades of Recommendation, Assessment, Development and Evaluation
      approach. A quantitative synthesis in the form of meta-analyses for measures of
      MVPA and health outcomes will be conducted where possible. DISCUSSION: This
      review will determine the effectiveness of e-health interventions in raising MVPA
      levels in working-age women in developed countries. It will form a contemporary,
      rigorously developed, and reliable research base for policy makers and
      stakeholders; and inform and influence the development and implementation of
      effective e-health interventions designed to increase MVPA levels and improve
      health outcomes in this population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42014009534.

PMID- 25589332
TI  - Controlled release from drug microparticles via solventless dry-polymer coating.
AB  - A novel solvent-less dry-polymer coating process employing high-intensity
      vibrations avoiding the use of liquid plasticizers, solvents, binders, and heat
      treatments is utilized for the purpose of controlled release. The main hypothesis
      is that such process having highly controllable processing intensity and time may
      be effective for coating particularly fine particles, 100 MUm and smaller via
      exploiting particle interactions between polymers and substrates in the dry
      state, while avoiding breakage yet achieving conformal coating. The method
      utilizes vibratory mixing to first layer micronized polymer onto active
      pharmaceutical ingredient (API) particles by virtue of van der Waals forces and
      to subsequently mechanically deform the polymer into a continuous film. As a
      practical example, ascorbic acid and ibuprofen microparticles, 50-500 MUm, are
      coated with the polymers polyethylene wax or carnauba wax, a generally recognized
      as safe material, resulting in controlled release on the order of seconds to
      hours. As a novelty, models are utilized to describe the coating layer thickness
      and the controlled-release behavior of the API, which occurs because of a
      diffusion-based mechanism. Such modeling would allow the design and control of
      the coating process with application for the controlled release of
      microparticles, particularly those less than 100 MUm, which are difficult to coat
      by conventional solvent coating methods.

PMID- 25589333
TI  - Risk of Bacterial Vaginosis Among Women With Herpes Simplex Virus Type 2
      Infection: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Bacterial vaginosis (BV) is a perturbation of vaginal flora
      characterized by reduced levels of lactobacilli and concomitant overgrowth of
      anaerobic bacterial species. BV is highly prevalent and associated with multiple
      adverse outcomes, including enhanced human immunodeficiency virus transmission.
      Because recent reports reveal that herpes simplex virus type 2 (HSV-2) infection
      may increase BV risk, we initiated a systematic review and meta-analysis of the
      link between HSV-2 infection and BV. METHODS: We searched the MEDLINE, EMBASE,
      and CENTRAL databases to identify articles posted before 1 December 2014. Two
      screeners independently reviewed the titles and abstracts of all identified
      articles, reviewed the full text of articles deemed potentially eligible, and
      extracted data from 14 cross-sectional and 3 prospective studies. Using random
      effects models, we computed separate pooled estimates for cross-sectional and
      prospective studies. RESULTS: The pooled odds ratio for cross-sectional studies
      was 1.60 (95% confidence interval, 1.32-1.94). Stronger support for the causal
      effect of HSV-2 infection on BV risk was revealed by the summary relative risk
      for the prospective studies, which was 1.55 (95% confidence interval, 1.30-1.84),
      with minimal heterogeneity (I(2) = 0). CONCLUSIONS: These analyses imply that HSV
      2 infection is an important BV risk factor. Pharmacologic HSV-2 suppression may
      reduce BV incidence and BV-associated adverse events.

PMID- 25589334
TI  - Effect of Immunosuppression on T-Helper 2 and B-Cell Responses to Influenza
      Vaccination.
AB  - BACKGROUND: Influenza vaccine immunogenicity is suboptimal in immunocompromised
      patients. However, there are limited data on the interplay of T- and B- cell
      responses to vaccination with simultaneous immunosuppression. METHODS: We
      collected peripheral blood mononuclear cells from transplant recipients before
      and 1 month after seasonal influenza vaccination. Before and after vaccination,
      H1N1-specific T- and B-cell activation were quantified with flow cytometry. We
      also developed a mathematical model using T- and B-cell markers and mycophenolate
      mofetil (MMF) dosage. RESULTS: In the 47 patients analyzed, seroconversion to
      H1N1 antigen was demonstrated in 34%. H1N1-specific interleukin 4 (IL-4)
      producing CD4(+) T-cell frequencies increased significantly after vaccination in
      53% of patients. Prevaccine expression of H1N1-induced HLA-DR and CD86 on B cells
      was high in patients who seroconverted. Seroconversion against H1N1 was strongly
      associated with HLA-DR expression on B cells, which was dependent on the increase
      between prevaccine and postvaccine H1N1-specific IL-4(+)CD4(+) T cells (R(2) =
      0.35). High doses of MMF (>= 2 g/d) led to lower seroconversion rates, smaller
      increase in H1N1-specific IL-4(+)CD4(+) T cells, and reduced HLA-DR expression on
      B cells. The mathematical model incorporating a MMF-inhibited positive feedback
      loop between H1N1-specific IL-4(+)CD4(+) T cells and HLA-DR expression on B cells
      captured seroconversion with high specificity. CONCLUSIONS: Seroconversion is
      associated with influenza-specific T-helper 2 and B-cell activation and seems to
      be modulated by MMF.

PMID- 25589335
TI  - Expanded cytotoxic T-cell lymphocytes target the latent HIV reservoir.
AB  - Enhanced human immunodeficiency virus (HIV)-specific immunity may be required for
      HIV eradication. Administration of autologous, ex vivo expanded, virus-specific,
      cytotoxic T-lymphocytes derived from HIV-infected patients on suppressive
      antiretroviral therapy (HXTCs) are a powerful tool for proof-of-concept studies.
      Broadly specific, polyclonal HXTCs resulting from ex vivo expansion demonstrated
      improved control of autologous reservoir virus compared to bulk CD8(+) T cells in
      viral inhibition assays. Furthermore, patient-derived HXTCs were able to clear
      latently infected autologous resting CD4(+) T cells following exposure to the
      latency-reversing agent, vorinostat. HXTCs will be ideal reagents to administer
      with precise control in future in vivo studies in combination with latency
      reversing agents. 

PMID- 25589336
TI  - Listeria arpJ gene modifies T helper type 2 subset differentiation.
AB  - BACKGROUND: Although the T-cell subset differentiation pathway has been
      characterized extensively from the view of host gene regulation, the effects of
      genes of the pathogen on T-cell subset differentiation during infection have yet
      to be elucidated. Especially, the bacterial genes that are responsible for this
      shift have not yet been determined. METHODS: Utilizing a single-gene-mutation
      Listeria panel, we investigated genes involved in the host-pathogen interaction
      that are required for the initiation of T-cell subset differentiation in the
      early phase of pathogen infection. RESULTS: We demonstrate that the induction of
      T helper types 1 and 2 (Th1 and Th2) subsets are separate phenomena and are
      mediated by distinct Listeria genes. We identified several candidate Listeria
      genes that appear to be involved in the host-Listeria interaction. Among them,
      arpJ is the strongest candidate gene for inhibiting Th2 subset induction.
      Furthermore, the analysis utilizing arpJ-deficient Listeria monocytogenes (Lm)
      revealed that the tumor necrosis factor (TNF) superfamily (Tnfsf) 9-TNF receptor
      superfamily (Tnfrsf) 9 interaction inhibits the Th2 response during Lm infection.
      CONCLUSIONS: arpJ is the candidate gene for inhibiting Th2 T-cell subset
      induction. The arpJ gene product influences the expression of Tnfsf/Tnfrsf on
      antigen-presenting cells and inhibits the Th2 T-cell subset differentiation
      during Listeria infection.

PMID- 25589337
TI  - Matrix Metalloproteinase-13 as a Target for Suppressing Corneal Ulceration Caused
      by Pseudomonas aeruginosa Infection.
AB  - PURPOSE: Pseudomonas aeruginosa keratitis is characterized by severe corneal
      ulceration. This study investigated whether matrix metalloproteinase-13 (MMP13)
      is involved in P. aeruginosa-induced corneal ulceration and whether it therefore
      can be targeted for preventing P. aeruginosa keratitis. METHODS: MMP13 expression
      in P. aeruginosa-infected C57BL/6 mouse corneas was assessed by quantitative
      polymerase chain reaction and immunohistochemistry analyses. An MMP13-inhibitor
      (MMP13i) was either injected subconjunctivally prior to or coapplied topically
      with gatifloxacin 16 hours after infection. Disease severity was assessed by
      corneal imaging, clinical scoring, bacterial burden, neutrophil infiltration, and
      CXCL2 expression. Corneal damage and infiltration were also determined by
      immunohistochemistry analysis and whole-mount confocal microscopy. RESULTS: P.
      aeruginosa infection induced an increased expression of MMP13 in mouse corneas
      from 6 to 24 hours after infection in a Toll-liked receptor 5-dependent manner.
      Subconjunctival injection of MMP13i prior to P. aeruginosa inoculation
      significantly decreased keratitis severity, as evidenced by preserved epithelium
      integrity and intact basement membrane, leading to reduced bacterial
      dissemination to the stroma. Furthermore, topical coapplication of MMP13i with
      gatifloxacin greatly improved disease outcomes, including accelerated opacity
      dissolution; decreased inflammation, cellular infiltration, and collagen
      disorganization; and basement membrane preservation. CONCLUSIONS: Elevated MMP13
      activity may contribute to P. aeruginosa keratitis through basement membrane
      degradation, and its inhibition could potentially be used as an adjunctive
      therapy to treat microbial keratitis and other mucosal infections.

PMID- 25589340
TI  - Effects of light quality and nutrient availability on accumulation of mycosporine
      like amino acids in Gymnodinium catenatum (Dinophycea).
AB  - A Portuguese Gymnodinium catenatum Graham strain was studied for its ultraviolet
      (UV) photoprotective pigments. This strain presented high absorption in the UVA
      region, in particular in the near UVA region around 370nm, followed by the far
      UVA region around 340nm. Absorption in the near-UVA increased when grown under
      fluorescent when compared to halogen light. This was even more relevant when
      grown under nutrient-limiting conditions, which even surpassed absorption in the
      blue region, closely resembling absorption in natural plankton assemblages
      reported in the literature. HPLC analysis for mycosporine-like amino acids
      (MAAs), revealed several UV photoprotective pigments common in other marine
      microalgae from the northwest Atlantic. Amongst the compounds absorbing in the
      far-UVA region, three were identified by spectra and retention time
      characteristics: shinorine, porphyra-334, and mycosporine-glycine. In the near
      UVA region, the unknown M-370 was usually the most abundant, followed by
      palythene. The proportional and absolute cellular concentrations of MAAs
      absorbing in the near-UVA region increased with fluorescent light when compared
      to halogen light. Additional experiments with light filtration suggest the set of
      MAAs absorbing in the near-UVA region seem to be regulated separately from the
      other set of MAAs absorbing in the far-UVA region, and those from the near-UVA
      region might be stimulated not only by UV but by blue light also. Nutrient
      availability affected profile: a shift towards MAAs with low nitrogen:carbon
      ratio (e.g.: mycosporine-glycine) was observed. As G. catenatum requires
      extensive UV-photoprotection over the entire UVA range, nitrogen availability
      might strongly restrict blooming, as MAAs are nitrogen-based. This UV sensitivity
      might help explaining its pronounced autumnal seasonality, tied to a reduced
      solar exposure. 

PMID- 25589339
TI  - Efficacy of ezetimibe is not related to NPC1L1 gene polymorphisms in a pilot
      study of Chilean hypercholesterolemic subjects.
AB  - BACKGROUND AND OBJECTIVE: Niemann-Pick C1 Like 1 (NPC1L1) is a multi
      transmembrane transport protein highly expressed in the small intestine. It
      mediates sterol transfer throughout the brush border membrane of enterocytes,
      becoming essential for intestinal cholesterol absorption and ensuing whole-body
      cholesterol homeostasis. This protein is targeted by ezetimibe, a potent
      cholesterol absorption inhibitor. Single nucleotide polymorphisms (SNPs) in
      NPC1L1 have been associated to variation in both plasma low-density lipoprotein
      (LDL) cholesterol levels and lipid-lowering medication with ezetimibe. However,
      there are no data evaluating the impact of NPC1L1 variants on Chilean subjects
      medicated with ezetimibe monotherapy. Therefore, we assessed the contribution of
      two unexplored NPC1L1 variants on plasma lipids and response to ezetimibe in
      Chilean hypercholesterolemic individuals. METHODS: Using PCR-restriction fragment
      length polymorphism (RFLP), we analyzed the SNP distribution of two common
      variants; -133A>G (rs17655652) and 1679C>G (rs2072183), and their relation with
      plasma lipids and lipid-lowering response to ezetimibe in 60 hypercholesterolemic
      Chilean subjects. RESULTS: Genotype distribution for the rs17655652 variant was
      AA 57 %, 40 % AG and 3 % GG, whereas for the rs2072183 SNP was 57 % CC, 35 % CG
      and 8 % GG. Minor allele frequencies (MAFs) were 0.23 and 0.26, respectively. No
      association was observed between NPC1L1 SNPs and baseline cholesterol. After
      therapy, none of the polymorphisms affected ezetimibe response in the studied
      cohort (P > 0.05). CONCLUSION: Data obtained indicates that polymorphisms
      rs17655652 and rs2072183 were not related to cholesterol variability. Also, lipid
      lowering response to ezetimibe is not impacted by the NPC1L1 polymorphisms
      studied in Chilean hypercholesterolemic subjects.

PMID- 25589341
TI  - Photochemical properties of gemifloxacin: a laser flash photolysis study.
AB  - The photochemical properties of gemifloxacin (GEFX), a fluoroquinolone
      antibacterial drug that exhibits phototoxicity toward biological substrates, were
      studied in aqueous solutions by laser flash photolysis (LFP) and pulse
      radiolysis. GEFX triplet state ((3)GEFX(*)) absorption spectra showed maximum
      absorption at 510nm. (3)GEFX(*) was quenched by naproxen (NAP) via energy
      transfer with a rate constant of 1.2*10(8)dm(3)mol(-1)s(-1). The energy of
      (3)GEFX(*) was 266kJmol(-1) and the transient absorption spectra showed direct
      evidence of electron transfer from 2'-deoxyguanosine-5'-monophosphate, N,N,N',N'
      tetramethyl-p-phenylenediamine, and tryptophan to (3)GEFX(*) with bimolecular
      reaction rate constants of 4.1*10(6), 2.0*10(7), and 2.2*10(7)dm(3)mol(-1)s(-1),
      respectively. The rate constants for reactions of GEFX with OH, eaq(-) were found
      to be 1.5*10(10) and 1.4*10(10)dm(3)mol(-1)s(-1), respectively. The mechanisms
      and products of the photosensitive damage of lysozyme were related to the GEFX
      concentration, irradiation time, and ambient conditions. 

PMID- 25589342
TI  - IgA deficiency and risk of cancer: a population-based matched cohort study.
AB  - PURPOSE: To investigate the risk of cancer in individuals with IgA deficiency
      compared with the general population. METHODS: Prospective nationwide population
      based cohort study. We identified 2320 individuals with IgA deficiency (IgA
      levels < 0.07 g/L) diagnosed between 1980 and 2010 in six Swedish university
      hospitals. Individuals with IgA deficiency were then matched on age, sex, place
      of residence, and year of diagnosis with up to 10 general population controls (n
      = 23,130). Through linkage with the Swedish Cancer Register we calculated
      conditional hazard ratios (HRs) for cancer diagnosed after IgA deficiency
      diagnosis in patients without a previous cancer diagnosis. RESULTS: During follow
      up, 125 individuals with IgA deficiency (61/10,000 person-years) and 984 controls
      (47/10,000 person-years) developed cancer (HR 1.31; 95%CI = 1.09-1.58). In cause
      specific analyses, we found an increased risk of any gastrointestinal cancer (HR
      = 1.64; 95%CI = 1.07-2.50), but not for lymphoproliferative malignancy (HR 1.68;
      95%CI = 0.89-3.19). Relative risk estimates for overall cancer were very high in
      the first year of follow-up (overall: HR = 2.80; 95%CI = 1.74-4.49), but failed
      to reach statistical significance thereafter. IgA deficiency diagnosed in
      childhood (n = 487) was not associated with overall cancer (HR = 3.26; 0.88
      12.03). CONCLUSIONS: Individuals with IgA deficiency are at a moderately
      increased risk of cancer, with excess risks of gastrointestinal cancer. This
      excess risk is highest just after diagnosis suggesting a degree of surveillance
      bias. Children with IgA deficiency were at no increased risk of cancer but the
      statistical power was limited in subanalyses.

PMID- 25589343
TI  - Determination of partial molar volumes from free energy perturbation theory.
AB  - Partial molar volume is an important thermodynamic property that gives insights
      into molecular size and intermolecular interactions in solution. Theoretical
      frameworks for determining the partial molar volume (V degrees ) of a solvated
      molecule generally apply Scaled Particle Theory or Kirkwood-Buff theory. With the
      current abilities to perform long molecular dynamics and Monte Carlo simulations,
      more direct methods are gaining popularity, such as computing V degrees  directly
      as the difference in computed volume from two simulations, one with a solute
      present and another without. Thermodynamically, V degrees  can also be determined
      as the pressure derivative of the free energy of solvation in the limit of
      infinite dilution. Both approaches are considered herein with the use of free
      energy perturbation (FEP) calculations to compute the necessary free energies of
      solvation at elevated pressures. Absolute and relative partial molar volumes are
      computed for benzene and benzene derivatives using the OPLS-AA force field. The
      mean unsigned error for all molecules is 2.8 cm(3) mol(-1). The present
      methodology should find use in many contexts such as the development and testing
      of force fields for use in computer simulations of organic and biomolecular
      systems, as a complement to related experimental studies, and to develop a deeper
      understanding of solute-solvent interactions. 

PMID- 25589344
TI  - Regulation of monocyte/macrophage polarisation by extracellular RNA.
AB  - Monocytes/macrophages respond to external stimuli with rapid changes in the
      expression of numerous inflammation-related genes to undergo polarisation towards
      the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype. We have previously
      shown that, independently of Toll-like receptor activation, extracellular RNA
      (eRNA) could exert pro-thrombotic and pro-inflammatory properties in the
      cardiovascular system to provoke cytokine mobilisation. Here, mouse bone marrow
      derived-macrophages (BMDM) differentiated with mouse macrophage-colony
      stimulating factor (M-CSF) were found to be skewed towards the M1 phenotype when
      exposed to eRNA. This resulted in up-regulated expression of inflammatory markers
      such as Tnf-alpha and Il-6, together with Il-12 and iNOS, whereas anti
      inflammatory genes such as chitinase-like proteins (Ym1/2) and macrophage mannose
      receptor-2 (Cd206) were significantly down-regulated. Human peripheral blood
      monocytes were treated with eRNA and analysed by micro-array analysis of the
      whole human genome, revealing an up-regulation of 79 genes by at least four-fold;
      27 of which are related to signal transduction and 15 genes associated with
      inflammatory response. In accordance with the proposed actions of eRNA as a pro
      inflammatory "alarm signal", these data shed light on the role of eRNA in the
      context of chronic inflammatory diseases such as atherosclerosis.

PMID- 25589345
TI  - Lysophosphatidic acid receptor LPAR6 supports the tumorigenicity of
      hepatocellular carcinoma.
AB  - The aberrant processes driving hepatocellular carcinoma (HCC) are not fully
      understood. Lysophosphatidic acid receptors (LPAR) are commonly overexpressed in
      HCC, but their contributions to malignant development are not well established.
      In this report, we show that aberrant expression of LPAR6 sustains tumorigenesis
      and growth of HCC. Overexpression of LPAR6 in HCC specimens associated with poor
      survival in a cohort of 128 patients with HCC. We took a genetic approach to
      elucidate how LPAR6 sustains the HCC tumorigenic process, including through an
      expression profiling analysis to identify genes under the control of LPAR6. RNAi
      mediated attenuation of LPAR6 impaired HCC tumorigenicity in tumor xenograft
      assays. Expression profiling and mechanistic analyses identified Pim-3 as a
      pathophysiologically relevant LPAR6 target gene. In nonmalignant cells where
      LPAR6 overexpression was sufficient to drive malignant character, Pim-3 was
      upregulated at the level of transcription initiation through a STAT3-dependent
      mechanism. A further analysis of HCC clinical specimens validated the connection
      between overexpression of LPAR6 and Pim-3, high proliferation rates, and poorer
      survival outcomes. Together, our findings establish LPAR6 as an important
      theranostic target in HCC tumorigenesis.

PMID- 25589348
TI  - Th9 cells: a novel CD4 T-cell subset in the immune war against cancer.
AB  - CD4 T cells are key components of the immune system that shape the anticancer
      immune response in animal models and in humans. The biology of CD4 T cells is
      complex because naive T cells can differentiate into various subpopulations with
      various functions. Recently, a new population called Th9 cells was described.
      These cells are characterized by their ability to produce IL9 and IL21. They were
      first described in the context of parasite infections and allergic processes.
      However, some reports described their presence in the tumor bed in mice and
      humans. Their high secretion of IL9 and IL21 in the tumor bed contributes to
      their anticancer functions. Indeed, these cytokines trigger the activation of
      dendritic cells, mast cells, natural killer cells, and CD8 T cells to mount an
      antitumor immune response, thus explaining the remarkable ability of Th9 cells to
      control tumor growth. This review summarizes the latest advances in the Th9 field
      in cancer and focuses on their potential role as new tool for cell therapy.

PMID- 25589346
TI  - Bruton tyrosine kinase is a therapeutic target in stem-like cells from multiple
      myeloma.
AB  - Ibrutinib (Imbruvica), a small-drug inhibitor of Bruton tyrosine kinase (BTK), is
      currently undergoing clinical testing in patients with multiple myeloma, yet
      important questions on the role of BTK in myeloma biology and treatment are
      outstanding. Using flow-sorted side population cells from human myeloma cell
      lines and multiple myeloma primary samples as surrogate for the elusive multiple
      myeloma stem cell, we found that elevated expression of BTK in myeloma cells
      leads to AKT/WNT/beta-catenin-dependent upregulation of key stemness genes (OCT4,
      SOX2, NANOG, and MYC) and enhanced self-renewal. Enforced transgenic expression
      of BTK in myeloma cells increased features of cancer stemness, including
      clonogenicity and resistance to widely used myeloma drugs, whereas inducible
      knockdown of BTK abolished them. Furthermore, overexpression of BTK in myeloma
      cells promoted tumor growth in laboratory mice and rendered side population
      derived tumors that contained high levels of BTK more sensitive to the selective,
      second-generation BTK inhibitor, CGI1746, than side population-derived tumors
      that harbored low levels of BTK. Taken together, these findings implicate BTK as
      a positive regulator of myeloma stemness and provide additional support for the
      clinical testing of BTK-targeted therapies in patients with myeloma.

PMID- 25589349
TI  - Novel insights into head and neck cancer using next-generation "omic"
      technologies.
AB  - Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous disease
      that develops via one of the two primary carcinogenic routes: chemical
      carcinogenesis through exposure to tobacco and alcohol or virally induced
      tumorigenesis. Human papillomavirus (HPV)-positive (HPV(+)) and HPV-negative
      (HPV(-)) HNSCCs represent distinct clinical entities, with the latter associated
      with significantly inferior outcome. The biologic basis of these different
      outcomes is an area of intense investigation; their therapeutic regimens are
      currently also being reevaluated, which would be significantly facilitated by
      reliable biomarkers for stratification. With the advent of the omics era and
      accelerated development of targeted therapies, there are unprecedented
      opportunities to address the challenges in the management of HNSCC. As summarized
      herein, side-by-side molecular characterization of HPV(+) versus HPV(-) HNSCC has
      revealed distinct molecular landscapes, novel prognostic signatures, and
      potentially targetable biologic pathways. In particular, we focus on the evidence
      acquired from genome-wide omics pertinent to our understanding of the clinical
      behavior of HNSCC and on insights into personalized treatment opportunities.
      Integrating, mining, and validating these data toward clinically meaningful
      outcomes for patients with HNSCC in conjunction with systematic verification of
      the functional relevance of these findings are critical steps toward the design
      of personalized therapies.

PMID- 25589351
TI  - Molecular dynamics of different polymer blends containing poly(2,6-dimethyl-1,4
      phenylene ether).
AB  - Detailed atomistic molecular dynamics simulations were performed to investigate
      the behavior of two different binary blends, a miscible system poly(2,6-dimethyl
      1,4-phenylene ether)-polystyrene (PPE-PS) and an immiscible system poly(2,6
      dimethyl-1,4-phenylene ether)-poly(methyl methacrylate) (PPE-PMMA). We compared
      these two blends to study how PPE behaves when blended with different polymers.
      In both cases, the structure and phase behavior of polymer melts were studied by
      means of radial distribution functions (RDFs). Radii of gyration illustrate the
      static properties. Packing features of the benzene rings were observed in PPE and
      PS, both PS and PPE were well dispersed over the whole time scale of simulation.
      Furthermore, there was a tendency for aggregation of PMMA chains in PPE-PMMA
      systems. The mean squared displacements of monomers and whole chains describe the
      mobility of polymers in various systems. 

PMID- 25589352
TI  - Controlled release of encapsulated bioactive volatiles by rupture of the capsule
      wall through the light-induced generation of a gas.
AB  - The encapsulation of photolabile 2-oxoacetates in core-shell microcapsules allows
      the light-induced, controlled release of bioactive compounds. On irradiation with
      UVA light these compounds degrade to generate an overpressure of gas inside the
      capsules, which expands or breaks the capsule wall. Headspace measurements
      confirmed the light-induced formation of CO and CO2 and the successful release of
      the bioactive compound, while optical microscopy demonstrated the formation of
      gas bubbles, the cleavage of the capsule wall, and the leakage of the oil phase
      out of the capsule. The efficiency of the delivery system depends on the
      structure of the 2-oxoacetate, the quantity used with respect to the thickness of
      the capsule wall, and the intensity of the irradiating UVA light. 

PMID- 25589350
TI  - Single-strand DNA-binding protein SSB1 facilitates TERT recruitment to telomeres
      and maintains telomere G-overhangs.
AB  - Proliferating mammalian stem and cancer cells express telomerase [telomerase
      reverse transcriptase (TERT)] in an effort to extend chromosomal G-overhangs and
      maintain telomere ends. Telomerase-expressing cells also have higher levels of
      the single-stranded DNA-binding protein SSB1, which has a critical role in DNA
      double-strand break (DSB) repair. Here, we report that SSB1 binds specifically to
      G-strand telomeric DNA in vitro and associates with telomeres in vivo. SSB1
      interacts with the TERT catalytic subunit and regulates its interaction with
      telomeres. Deletion of SSB1 reduces TERT interaction with telomeres and leads to
      G-overhang loss. Although SSB1 is recruited to DSB sites, we found no
      corresponding change in TERT levels at these sites, implying that SSB1-TERT
      interaction relies upon a specific chromatin structure or context. Our findings
      offer an explanation for how telomerase is recruited to telomeres to facilitate G
      strand DNA extension, a critical step in maintaining telomere ends and cell
      viability in all cancer cells. Cancer Res; 75(5); 858-69. (c)2015 AACR. 

PMID- 25589353
TI  - [Histological spectrum of malignant melanoma].
AB  - The diagnosis of melanocytic tumors is one of the most problematic areas in
      dermatology and diagnostic pathology. Melanoma is a malignant melanocytic tumor
      and the risk for metastasis and associated mortality is mainly dependent on tumor
      thickness and depth of invasion. Early recognition and correct diagnosis is
      therefore important for successful and effective treatment. The correct diagnosis
      of melanoma is, however, challenging due to the wide morphological spectrum.
      Historically, the disease was subdivided into superficial spreading, nodular,
      lentigo maligna and acral lentiginous melanoma but many more subtypes have
      subsequently been added. Some of these melanoma variants also show differences
      relating to the genetic background, clinical presentation, prognosis and
      treatment and may be associated with a specific differential diagnosis. In this
      article four of these melanoma variants, desmoplastic melanoma, nevoid melanoma,
      malignant blue nevus and pigment synthesizing melanoma will be discussed in more
      detail. 

PMID- 25589354
TI  - [Cutaneous angiosarcoma: new aspects].
AB  - Cutaneous angiosarcoma is an aggressive endothelial cell neoplasm with a high
      associated mortality. Reliable and confident diagnosis is necessary but
      frequently challenging due to the wide morphological spectrum and broad
      differential diagnosis of the disease. Furthermore, the final diagnosis often
      relies on immunohistochemical evidence of endothelial cell differentiation which
      is further complicated by the lack of sensitivity and specificity of conventional
      endothelial cell markers. The following article outlines the clinical and
      histological spectrum of cutaneous angiosarcoma with emphasis on novel findings
      relating to immunohistochemistry and molecular genetics in the context of the
      relevant differential diagnosis. 

PMID- 25589355
TI  - [Cutaneous lymphomas: new entities and rare variants].
AB  - Primary cutaneous lymphomas are the second most common group of extranodal non
      Hodgkin lymphomas. Recently several new variants and entities have been described
      but have not yet become part of the World Health Organization (WHO)
      classification. These forms include the granulomatous form of mycosis fungoides,
      which is associated with a poorer prognosis, as well as indolent CD8+
      lymphoproliferations on the head and at acral localizations. Within the group of
      cutaneous CD30+ lymphoproliferative disorders, new histological types of
      lymphomatoid papulosis have been identified, such as type D (CD8+ epidermotropic)
      and type E (angioinvasive) which simulate aggressive lymphomas. Cutaneous
      peripheral T-cell lymphomas are a prognostically heterogeneous group of cutaneous
      lymphomas. The cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma
      and cutaneous gamma/delta T-cell lymphoma are very aggressive neoplasms, whereas
      cutaneous CD4+ small to medium-sized T-cell lymphoma in its solitary or localized
      form represents an indolent lymphoproliferation: the terminology, histogenesis
      and differentiation from nodular T-cell pseudolymphoma are still a matter of
      debate. Among B-cell lymphomas, disorders associated with Epstein-Barr virus
      (EBV) are discussed focusing on EBV diffuse large B-cell lymphoma of the elderly
      and EBV-associated mucocutaneous ulcer. This review describes the clinical,
      histological and immunophenotypic features of new and rare entities and variants
      of cutaneous lymphomas and highlights the impact of the clinicopathological
      correlation in the diagnostic process. 

PMID- 25589357
TI  - [Health-related quality of life: a pivotal endpoint in benefit assessment of
      medical procedures].
AB  - BACKGROUND: According to German law, health-related quality of life is a relevant
      criterion in the early assessment of the benefits of drug treatment. In spite of
      its regulatory importance, the role of quality of life assessment in quantifying
      the additional benefits of novel vs standard treatments is not yet clear.
      OBJECTIVES: The paper is aimed at analyzing the theoretical foundation, the
      methodological foundation, and the empirical evaluation of the criterion "quality
      of life" in recent benefit dossiers, as published by the Federal Joint Committee
      (G-BA) and the German Institute for Quality and Efficiency in Health Care
      (IQWiG). MATERIALS AND METHODS: Benefit dossiers assessed by the end of 2013 were
      quantitatively analyzed regarding the choice, frequency of use, and consequences
      of quality of life assessment. RESULTS: In 59 of the 66 dossiers quality of life
      assessment was performed, frequently using the EQ-5D (n = 16 procedures) and the
      SF-36 (n = 8 procedures). Of the 107 evaluations of the subpopulation within
      these 59 dossiers, in only 2 cases was an additional benefit due to the quality
      of life declared by the IQWiG and G-BA. CONCLUSIONS: In spite of the acceptance
      of quality of life measures and their inclusion in the dossiers, they have rarely
      been the basis for the declaration of additional benefits. This reluctance does
      not stem from the availability of instruments, but results from problems in their
      selection, the design and conduct of the study, data interpretation, together
      with shortcomings regarding the statistical and clinical significance of quality
      of life data.

PMID- 25589356
TI  - [Fibrohistiocytic tumors of the skin: a heterogeneous group of superficially
      located mesenchymal neoplasms].
AB  - So-called fibrohistiocytic tumors of the skin comprise a heterogeneous spectrum
      of superficially located neoplasms that often show fibroblastic and/or
      myofibroblastic differentiation. In this review clinicopathologically important
      variants of dermatofibroma and dermatofibrosarcoma protuberans and their
      differential diagnoses are discussed in detail. In addition, the
      clinicopathological features of atypical fibroxanthoma, angiomatoid fibrous
      histiocytoma, plexiform fibrohistiocytic tumors and pleomorphic dermal sarcoma
      are presented. Entities that have to be considered in the differential diagnosis
      are also mentioned. 

PMID- 25589358
TI  - Elemental biochemical analysis of the polysaccharides in the extracellular matrix
      of the yeast Saccharomyces cerevisiae.
AB  - In yeast multicellular aggregates, such as biofilms and colonies, cells are
      supported by a yeast extracellular matrix (yECM) of glycosidic nature, the
      composition of which is mostly unknown. Saccharomyces cerevisiae ECM was
      produced, extracted and partitioned. An analytical-grade pure glycoside fraction
      was obtained, fractionated by anionic exchange liquid chromatography and analyzed
      by gas chromatography-mass spectrometry and polyacrylamide gel electrophoresis.
      Two different molecular weight polysaccharides were found, composed of glucose,
      mannose and small relative amounts of galactose. One of the polysaccharides had a
      low molecular weight, compatible with the association with glycoproteins
      abundantly occurring in yECM. In addition, these polysaccharide species were
      separated by diaminopropane agarose gel electrophoresis and induced metachromatic
      shift, suggesting chemical substitution, which was corroborated by
      anticoagulation activity. This was shown to be associated with the double
      deletion of the yeast homologues of the mammalian Hedgehog modulators Hhatl and
      Hhat, respectively yeast Gup1 and Gup2. These results pioneer the study of the
      molecular biology of the ECM supporting S. cerevisiae multicellular aggregates
      such as biofilms. 

PMID- 25589359
TI  - Longitudinal impact of sleep on overweight and obesity in children and
      adolescents: a systematic review and bias-adjusted meta-analysis.
AB  - Short sleep duration is considered a potential risk for overweight/obesity in
      childhood and adolescence. However, most of the evidence on this topic is
      obtained from cross-sectional studies; therefore, the nature and extent of the
      longitudinal associations are unclear. This study explores the prospective
      association between short sleep and overweight/obesity in young subjects. The
      MEDLINE, EMBASE, Pubmed, and CINAHL databases were searched for English-language
      articles, published until May 2014, reporting longitudinal association between
      sleep and body mass index (BMI) in children and adolescents. Recommendations of
      the Sleep Health Foundation were used to standardize reference sleep duration.
      Sleep category, with sleep duration less than the reference sleep, was considered
      as the short sleep category. Meta-analysis was conducted to explore the
      association between short sleep and overweight/obesity. A review of 22
      longitudinal studies, with subjects from diverse backgrounds, suggested an
      inverse association between sleep duration and BMI. Meta-analysis of 11
      longitudinal studies, comprising 24,821 participants, revealed that subjects
      sleeping for short duration had twice the risk of being overweight/obese,
      compared with subjects sleeping for long duration (odds ratio 2.15; 95%
      confidence interval: 1.64-2.81). This study provides evidence that short sleep
      duration in young subjects is significantly associated with future
      overweight/obesity. 

PMID- 25589360
TI  - The Elsevier Trophoblast Research Award Lecture: Importance of metzincin
      proteases in trophoblast biology and placental development: a focus on ADAM12.
AB  - Placental development is a highly regulated process requiring signals from both
      fetal and maternal uterine compartments. Within this complex system,
      trophoblasts, placental cells of epithelial lineage, form the maternal-fetal
      interface controlling nutrient, gas and waste exchange. The commitment of
      progenitor villous cytotrophoblasts to differentiate into diverse trophoblast
      subsets is a fundamental process in placental development. Differentiation of
      trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential
      for uterine arterial remodeling and placental function. Inadequate placentation,
      characterized by defects in trophoblast differentiation, may underlie the
      earliest cellular events driving pregnancy disorders such as preeclampsia and
      fetal growth restriction. Molecularly, invasive trophoblasts acquire
      characteristics defined by profound alterations in cell-cell and cell-matrix
      adhesion, cytoskeletal reorganization and production of proteolytic factors. To
      date, most studies have investigated the importance of the matrix
      metalloproteinases (MMPs) and their ability to efficiently remodel components of
      the extracellular matrix (ECM). However, it is now becoming clear that besides
      MMPs, other related proteases regulate trophoblast invasion via mechanisms other
      than ECM turnover. In this review, we will summarize the current knowledge on the
      regulation of trophoblast invasion by members of the metzincin family of
      metalloproteinases. Specifically, we will discuss the emerging roles that A
      Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a
      particular focus on the ADAM subtype, ADAM12. 

PMID- 25589363
TI  - Enhancing and suppressing effects of an inner droplet on deformation of a double
      emulsion droplet under shear.
AB  - We combine experimental investigation with numerical simulation to explore
      fundamental hydrodynamic effects of an inner droplet on deformation of a double
      emulsion droplet under shear. The transient deformation oscillation is found to
      be intensified by the inner droplet. Especially, we demonstrate that the double
      emulsion droplet can exhibit both larger and smaller steady deformation than the
      single-phase droplet, which arises from the competition between the coexisting
      enhancing and suppressing effects by the inner droplet on the deformation. We
      further provide a regime diagram to quantitatively recognize the respective
      dominant regime of these two effects, depending on the capillary number and
      radius ratio of the inner droplet to the outer one. 

PMID- 25589362
TI  - In vitro characterization of the digestive stress response and immunomodulatory
      properties of microorganisms isolated from smear-ripened cheese.
AB  - Thirty-six microorganisms (twenty-one bacteria, twelve yeasts and three fungi)
      were isolated from surface-ripened cheeses and subjected to in vitro digestive
      stress. The approach mimicked gastric and/or duodenal digestion. Lactobacillus
      rhamnosus GG, Escherichia coli Nissle 1917 and Saccharomyces boulardii were used
      as reference strains. We studied the microorganisms grown separately in culture
      medium and then included (or not) in a rennet gel. The microorganisms'
      immunomodulatory abilities were also assessed by profiling cytokine induction in
      human peripheral blood mononuclear cells (PBMCs). The loss of viability was less
      than 1 log CFU/mL for yeasts under all conditions. In contrast, Gram-negative
      bacteria survived gastric and/or duodenal stress well but most of the Gram
      positive bacteria were more sensitive (especially to gastric stress). Inclusion
      of sensitive Gram-positive bacteria in rennet gel dramatically improved gastric
      survival, when compared with a non-included cultured (with a 4 log CFU/mL change
      in survival). However, the rennet gel did not protect the bacteria against
      duodenal stress. The PBMC cytokine assay tests showed that the response to yeasts
      was usually anti-inflammatory, whereas the response to bacteria varied from one
      strain to another.

PMID- 25589365
TI  - Direct bandgap transition in many-layer MoS2 by plasma-induced layer decoupling.
AB  - We report a robust method for engineering the optoelectronic properties of many
      layer MoS2 using low-energy oxygen plasma treatment. Gas phase treatment of MoS2
      with oxygen radicals generated in an upstream N2 -O2 plasma is shown to enhance
      the photoluminescence (PL) of many-layer, mechanically exfoliated MoS2 flakes by
      up to 20 times, without reducing the layer thickness of the material. A blueshift
      in the PL spectra and narrowing of linewidth are consistent with a transition of
      MoS2 from indirect to direct bandgap material. Atomic force microscopy and Raman
      spectra reveal that the flake thickness actually increases as a result of the
      plasma treatment, indicating an increase in the interlayer separation in MoS2 .
      Ab initio calculations reveal that the increased interlayer separation is
      sufficient to decouple the electronic states in individual layers, leading to a
      transition from an indirect to direct gap semiconductor. With optimized plasma
      treatment parameters, we observed enhanced PL signals for 32 out of 35 many-layer
      MoS2 flakes (2-15 layers) tested, indicating that this method is robust and
      scalable. Monolayer MoS2 , while direct bandgap, has a small optical density,
      which limits its potential use in practical devices. The results presented here
      provide a material with the direct bandgap of monolayer MoS2 , without reducing
      sample thickness, and hence optical density. 

PMID- 25589361
TI  - Reduced expression of the epidermal growth factor signaling system in
      preeclampsia.
AB  - INTRODUCTION: The epidermal growth factor (EGF) signaling system regulates
      trophoblast differentiation, and its disruption could contribute to perinatal
      disease. We hypothesized that this pathway is altered in preeclampsia, a disorder
      associated with trophoblast apoptosis and failure to invade and remodel the
      uterine spiral arteries. METHODS: Six EGF family peptides and a truncated EGF
      receptor splice variant (p110/EGFR) were examined using immunohistochemistry in
      the trophoblast of placentas (N = 76) from women with preeclampsia, and compared
      to placentas from women of similar gestational age (GA) with preterm labor (PTL)
      or small for gestational age (SGA) fetuses, as well as normal term placentas.
      EGF, transforming growth factor-alpha (TGFA), and heparin-binding EGF-like growth
      factor (HBEGF) were evaluated using ELISA in maternal plasma from another 20
      pregnancies with or without preeclampsia. Cell death was evaluated in the HTR
      8/SVneo human cytotrophoblast cell line using TUNEL to evaluate the protective
      effects of EGF peptides. RESULTS: Trophoblast HBEGF, TGFA, and EGF were
      significantly reduced in preeclampsia compared to PTL and SGA, while p110/EGFR
      accumulated significantly on the surface of the chorionic villi (p < 0.05).
      Plasma EGF levels were significantly decreased in preeclamptic patients, compared
      to non-preeclamptic patients (p < 0.05). HBEGF, EGF, TGFA, epiregulin, and
      betacellulin each blocked cytotrophoblast cell death in vitro (p < 0.05).
      DISCUSSION: Three members of the EGF family are dysregulated in placentas with
      preeclampsia, whereas p110/EGFR, a potential EGF receptor antagonist, is
      overexpressed. These findings are consistent with the concept that disruption of
      the EGF signaling system contributes to aberrant trophoblast development
      associated with preeclampsia.

PMID- 25589364
TI  - Reduced cerebrospinal fluid ethanolamine concentration in major depressive
      disorder.
AB  - Amino acids play key roles in the function of the central nervous system, and
      their alterations are implicated in psychiatric disorders. In the search for a
      biomarker for major depressive disorder (MDD), we used high-performance liquid
      chromatography to measure amino acids and related molecules in the cerebrospinal
      fluid (CSF) of 52 patients with MDD (42 depressed and 10 remitted; DSM-IV) and 54
      matched controls. Significant differences were found in four amino acid
      concentrations between the depressed patients and controls. After Bonferroni
      correction, only ethanolamine (EA) levels remained significantly reduced in
      depressed patients (nominal P = 0.0000011). A substantial proportion of the
      depressed patients (40.5%) showed abnormally low CSF EA levels (<12.1 MUM) (P =
      0.000033; OR = 11.6, 95% CI: 3.1-43.2). When patients with low EA and those with
      high EA levels were compared, the former had higher scores for overall depression
      severity (P = 0.0033) and 'Somatic Anxiety' symptoms (P = 0.00026). In
      unmedicated subjects, CSF EA levels showed a significant positive correlation
      with levels of homovanillic acid (P = 0.0030) and 5-hydroxyindoleacetic acid (P =
      0.019). To our knowledge, this is the first study showing that patients with MDD
      have significantly lower CSF EA concentrations compared with control subjects.
      CSF EA could be a state-dependent biomarker for a subtype of MDD.

PMID- 25589366
TI  - Thrombophilic state in young patients with acute myocardial infarction.
AB  - The prevalence of thrombophilia and dyslipidemia among young survivors of acute
      coronary syndrome has not been clearly defined. The purpose of the current study
      was to investigate the prevalence of multiple markers of thrombophilia and
      dyslipidemia in a cohort of consecutive young survivors of acute coronary
      syndrome. The study cohort included 156 consecutive young patients (men <45 and
      women <50 years), admitted to the intensive cardiac care unit with newly
      diagnosed acute coronary syndrome. Analysis included baseline, clinical and
      epidemiological characteristics, angiographic coronary anatomy, echocardiographic
      evaluation, extensive lipid and thrombophilia laboratory profiles, and in
      hospital and 1-year clinical outcomes for all patients. Acute myocardial
      infarction was diagnosed in 142 (92 %) patients, of whom 108 (72 %) had ST
      segment elevation. Eighteen (12 %) patients had no traditional risk factors. Low
      levels of high-density lipoprotein (<40 mg/dL) were found in 101 (65 %) patients,
      and 49 (34 %) patients had elevated levels of lipoprotein(a) (Lp(a)) (>30 mg/dL).
      Eighteen (12 %) patients were diagnosed with antiphospholipid antibody syndrome
      (APS), and 73 (47 %) had at least one laboratory finding consistent with
      thrombophilia. Patients with APS had significantly higher levels of Lp(a) (46 +/-
      32 vs. 29 +/- 31 mg/dL, p = 0.005). APS is a common prothrombotic state found in
      young survivors of acute coronary syndrome. Lp(a) levels are elevated among APS
      patients who present with premature acute coronary syndrome.

PMID- 25589367
TI  - Application of mobile technology for improving expanded program on immunization
      among highland minority and stateless populations in northern Thailand border.
AB  - BACKGROUND: Studies of undervaccinated children of minority/stateless populations
      have highlighted significant barriers at individual, community, and state levels.
      These include geography-related difficulties, poverty, and social norms/beliefs.
      OBJECTIVE: The objective of this study was to assess project outcomes regarding
      immunization coverage, as well as maternal attitudes and practices toward
      immunization. METHODS: The "StatelessVac" project was conducted in Thailand
      Myanmar-Laos border areas using cell phone-based mechanisms to increase
      immunization coverage by incorporating phone-to-phone information sharing for
      both identification and prevention. With limitation of the study among vulnerable
      populations in low-resource settings, the pre/post assessments without comparison
      group were conducted. Immunization coverage was collected from routine monthly
      reports while behavior-change outcomes were from repeat surveys. RESULTS: This
      study revealed potential benefits of the initiative for case identification;
      immunization coverage showed an improved trend. Prevention strategies were
      successfully integrated into the routine health care workflows of immunization
      activities at point-of-care. A behavior-change-communication package contributes
      significantly in raising both concern and awareness in relation to child care.
      CONCLUSIONS: The mobile technology has proven to be an effective mechanism in
      improving a children's immunization program among these hard-to-reach
      populations. Part of the intervention has now been revised for use at health
      centers across the country.

PMID- 25589368
TI  - EPA's proposed Worker Protection Standard and the burdens of the past.
AB  - BACKGROUND: An Environmental Protection Agency (EPA) recommendation for extensive
      changes to the Agency's 40-year-old Worker Protection Standard is currently
      stalled in the "proposed rule" stage. The proposal, which was available for
      public comment until 18 August, would improve safety, training, and hazard
      communication policies for agricultural pesticides. Exposure to hazards,
      including high heat, heavy machinery, stoop labor, and pesticides, makes
      occupational illness uncommonly common among the USA's estimated 2.5 million farm
      workers. OBJECTIVES: To consider the proposed revisions' likelihood of addressing
      historical gaps in farmworker protection. METHODS: The proposal was compared to
      the existing Worker Protection Standard, and key aspects were analyzed in
      relation to existing science on farm labor hazards, as well as historic
      occupational health, labor and immigration policy. RESULTS: US law historically
      has left farm workers largely unprotected. These exclusions and delays have been
      tolerated in part thanks to the myth of the independent family farmer, but more
      significant is the stingy nativism that presumes to benefit from immigrant labor
      without assuming any responsibility to protect the humans who provide it. In the
      first half of the 1970s, workers lobbied for robust protections, but rule making
      was impeded by lack of data and by the disproportionate influence of agricultural
      employers who sought minimal regulation. In 1974, the EPA passed the first Worker
      Protection Standard for farm workers. Key aspects of the proposed revision
      include stronger protections against drift and re-entry exposures, better
      information provision and training, and increased protections for workers under
      16 years. CONCLUSIONS: The proposed changes represent an improvement over
      existing legislation, but do not go far enough. The revision should be
      strengthened along lines suggested by farm workers themselves, and other labor
      laws must also be amended to give the men, women, and children who work in the
      fields of this country full rights and protections.

PMID- 25589369
TI  - Quantifying the costs and benefits of occupational health and safety
      interventions at a Bangladesh shipbuilding company.
AB  - BACKGROUND: This study is the first cost-benefit analysis (CBA) of occupational
      health and safety (OHS) in a low-income country. It focuses on one of the largest
      shipbuilding companies in Bangladesh, where globally recognised Occupational
      Health and Safety Advisory Services (OHSAS) 18001 certification was achieved in
      2012. OBJECTIVES: The study examines the relative costs of implementing OHS
      measures against qualitative and quantifiable benefits of implementation in order
      to determine whether OHSAS measures are economically advantageous. METHODS:
      Quantifying past costs and benefits and discounting future ones, this study looks
      at the returns of OHS measures at Western Marine Shipbuilding Company Ltd.
      RESULTS: Costs included investments in workplace and environmental safety, a new
      clinic that also serves the community, and personal protective equipment (PPE)
      and training. The results are impressive: previously high injury statistics
      dropped to close to zero. CONCLUSIONS: OHS measures decrease injuries, increase
      efficiency, and bring income security to workers' families. Certification has
      proven a competitive edge for the shipyard, resulting in access to greater
      markets. Intangible benefits such as trust, motivation and security are deemed
      crucial in the CBA, and this study finds the high investments made are difficult
      to offset with quantifiable benefits alone.

PMID- 25589371
TI  - Maternal Functioning Differences Based on ADHD Subtype.
AB  - OBJECTIVE: Maternal functioning differences in parenting stress, parental
      efficacy, and parenting behaviors were examined for mothers of children with
      ADHD. METHOD: Participants included 29 mothers of children with ADHD,
      Predominantly Inattentive Type (ADHD-I) and 38 mothers of children with ADHD,
      Predominantly Hyperactive-Impulsive or Combined Type (ADHD-HI/C). RESULTS:
      Findings suggest that mothers of children with ADHD-HI/C reported significantly
      greater parenting stress and engaged in more negative parenting behaviors than
      mothers of children with ADHD-I. CONCLUSION: This study suggests that tailoring
      behavioral parent training based on ADHD subtype may be particularly helpful for
      parents of children with ADHD-HI/C.

PMID- 25589370
TI  - Isoprenoid geranylgeraniol: the influence on cell characteristics of endothelial
      progenitor cells after bisphosphonate therapy in vitro.
AB  - OBJECTIVES: Geranylgeraniol (GGOH) has been reported as a potential treatment
      option for bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ). The aim
      of this study was to analyze the effects of GGOH on endothelial progenitor cells
      (EPC) after bisphosphonate treatment in vitro. MATERIALS AND METHODS: EPC were
      incubated with different nitrogen (N-BPs: ibandronate, pamidronate, zoledronate)
      and a non-nitrogen-containing bisphosphonates (NN-BP: clodronate) with and
      without GGOH. Cell viability was measured by MTT and PrestoBlue assay. Migration
      ability was analyzed with a Boyden and Scratch assay. Apoptosis rates were
      determined by colony-forming, Tunel and ToxiLight assays. RESULTS: Negative
      effects of N-BPs on EPC were shown in all tests without GGOH. The substitution of
      GGOH demonstrated significantly increased cell viability (MTT: p each N-BP
      <=0.004; PrestoBlue: p each N-BP <0.001) and migration ability (Boyden: p each N
      BP <0.001; Scratch: p each N-BP <0.001). Concerning the apoptosis rates,
      increased EPC colony densities (p each N-BP <=0.009), decreased numbers of
      apoptotic cells in the Tunel assay (p each N-BP <0.001), and a decreased
      adenylate kinase release in the ToxiLight assay (p each N-BP <=0.03) were
      observed. For the clodronate-treated cells, no significant differences could be
      detected with or without GGOH in any assay (p each N-BP/NN-BP >0.05).
      CONCLUSIONS: GGOH cell treatment reversed the negative effects of bisphosphonates
      on EPC. CLINICAL RELEVANCE: These findings support the hypothesis that systemic
      or local GGOH treatment might lead to new therapeutic strategies for BP-ONJ.

PMID- 25589372
TI  - Evaluation of Cartilage Repair by Mesenchymal Stem Cells Seeded on a PEOT/PBT
      Scaffold in an Osteochondral Defect.
AB  - The main objective of this study was to evaluate the effectiveness of a
      mesenchymal stem cell (MSC)-seeded polyethylene-oxide-terephthalate/polybutylene
      terephthalate (PEOT/PBT) scaffold for cartilage tissue repair in an osteochondral
      defect using a rabbit model. Material characterisation using scanning electron
      microscopy indicated that the scaffold had a 3D architecture characteristic of
      the additive manufacturing fabrication method, with a strut diameter of 296 +/-
      52 MUm and a pore size of 512 +/- 22 MUm * 476 +/- 25 MUm * 180 +/- 30 MUm. In
      vitro optimisation revealed that the scaffold did not generate an adverse cell
      response, optimal cell loading conditions were achieved using 50 MUg/ml
      fibronectin and a cell seeding density of 25 * 10(6) cells/ml and
      glycosaminoglycan (GAG) accumulation after 28 days culture in the presence of
      TGFbeta3 indicated positive chondrogenesis. Cell-seeded scaffolds were implanted
      in osteochondral defects for 12 weeks, with cell-free scaffolds and empty defects
      employed as controls. On examination of toluidine blue staining for
      chondrogenesis and GAG accumulation, both the empty defect and the cell-seeded
      scaffold appeared to promote repair. However, the empty defect and the cell-free
      scaffold stained positive for collagen type I or fibrocartilage, while the cell
      seeded scaffold stained positive for collagen type II indicative of hyaline
      cartilage and was statistically better than the cell-free scaffold in the blinded
      histological evaluation. In summary, MSCs in combination with a 3D PEOT/PBT
      scaffold created a reparative environment for cartilage repair. 

PMID- 25589373
TI  - The Changes of Trunk Motion Rhythm and Spinal Loading During Trunk Flexion and
      Extension Motions Caused by Lumbar Muscle Fatigue.
AB  - Previous studies indicated that lumbar extensor muscle fatigue could potentially
      affect lumbar-pelvic rhythm and influence spinal loading during trunk motions. In
      this study, the effects of lumbar extensor muscle fatigue on the normalized
      lumbar-pelvic rotation rhythm and the associated L5/S1 joint loading during
      weight lifting and lowering tasks were investigated. Thirteen volunteers
      performed lifting and lowering of a 20-lbs box both before and after lumbar
      extensor muscle fatigue, which was generated through a static weight holding
      task. The normalized lumbar-pelvic motion ratio (L/P ratio) and the external
      moment on the L5/S1 joint were calculated and compared. Results showed that
      subjects demonstrated significantly larger normalized L/P ratios during both
      weight lifting and lowering tasks with the influence of fatigue. In addition,
      although the spinal loadings remain unchanged at the beginning and ending of both
      lifting and lowering motions, significantly larger L5/S1 joint moments were
      observed during both motions after fatigue. Such changes indicate potentially
      elevated risk of back injury. In a clinical setting, the current results
      demonstrated that lumbar muscle fatigue could cause transient changes in lumbar
      pelvic motion rhythm. Therefore, lumbar muscle fatigue must be avoided when using
      lumbar-pelvic motion rhythms for patient diagnosis or rehabilitation assessment. 

PMID- 25589374
TI  - An In Vitro Evaluation of Emboli Trajectories Within a Three-Dimensional Physical
      Model of the Circle of Willis Under Cerebral Blood Flow Conditions.
AB  - In vitro simulations of the trajectory and lodgement locations of emboli within
      the circle of Willis (CoW) are crucial in understanding the associated
      hemodynamic effects in stroke patients. A clot was fabricated from the hemolymph
      of a crustacean species. Clots were injected into the internal carotid artery via
      a cerebral flow facility housing a manufactured CoW human model. The trajectory
      of the clot was tracked and its hemodynamic effects monitored. The clots traveled
      with an average velocity of 88 mm/s along the ipsilateral side with momentary
      pauses along high curvature regions before finally lodging within the distal
      branches of the ipsilateral middle cerebral artery (MCA). These clots either
      elongated along the branching vessels or compressed against a bifurcation point.
      A blocked M1-segment of the MCA reduced the efferent blood pressure and flow
      rates by (15-77%) and (20-100%) respectively with a re-distribution of the flow
      towards the other efferent vessels. Mimicking blood clots with crustacean
      hemolymph provides a much lower biohazard risk than using human or mammalian
      blood clots and a superior alternative to synthetic materials. The geometry of
      the distal MCA vasculature will determine the end morphology of the lodged clot.
      Clotting severely reduces the distal flow rates and pressures. 

PMID- 25589375
TI  - Tap density equations of granular powders based on the rate process theory and
      the free volume concept.
AB  - The tap density of a granular powder is often linked to the flowability via the
      Carr index that measures how tight a powder can be packed, under an assumption
      that more easily packed powders usually flow poorly. Understanding how particles
      are packed is important for revealing why a powder flows better than others.
      There are two types of empirical equations that were proposed to fit the
      experimental data of packing fractions vs. numbers of taps in the literature: the
      inverse logarithmic and the stretched exponential. Using the rate process theory
      and the free volume concept under the assumption that particles will obey similar
      thermodynamic laws during the tapping process if the "granular temperature" is
      defined in a different way, we obtain the tap density equations, and they are
      reducible to the two empirical equations currently widely used in literature. Our
      equations could potentially fit experimental data better with an additional
      adjustable parameter. The tapping amplitude and frequency, the weight of the
      granular materials, and the environmental temperature are grouped into this
      parameter that weighs the pace of the packing process. The current results, in
      conjunction with our previous findings, may imply that both "dry" (granular) and
      "wet" (colloidal and polymeric) particle systems are governed by the same
      physical mechanisms in term of the role of the free volume and how particles
      behave (a rate controlled process). 

PMID- 25589376
TI  - Risk aversion, time preference and health production: theory and empirical
      evidence from Cambodia.
AB  - This paper quantifies the relationship between risk aversion and discount rates
      on the one hand and height and weight on the other. It studies this link in the
      context of poor households in Cambodia. Evidence is based on an original dataset
      that contains both experimental measures of risk taking and impatience along with
      anthropometric measurements of children and adults. The aim of the paper is to
      (i) explore the importance of risk and time preferences in explaining
      undernutrition and (ii) compare the evidence stemming from poor households to
      strikingly similar findings from industrialized countries. It uses an inter
      generational approach to explain observed correlations in adults and children
      that is inspired by the height premium on labor markets. Parents can invest in
      the health capital of their child to increase future earnings and their
      consumption when old: better nutrition during infancy translates into better
      human capital and better wages, and ultimately better financial means to take
      care of elderly parents. However this investment is subject to considerable
      uncertainty, since parents neither perfectly foresee economic conditions when the
      child starts earning nor fully observe the ability to transform nutritional
      investments into long-term health capital. As a result, risk taking households
      have taller and heavier children. Conversely, impatience does not affect child
      health. In the case of adults, only weight and the body mass index (BMI), but not
      height, are positively and moderately correlated with risk taking and impatience.

PMID- 25589377
TI  - Many cancer deaths could be eliminated by greater awareness and access to latest
      treatments, report says.

PMID- 25589378
TI  - Major depressive episodes over the course of 7 years and hippocampal subfield
      volumes at 7 tesla MRI: the PREDICT-MR study.
AB  - INTRODUCTION: Smaller hippocampal volumes have been associated with major
      depressive disorder (MDD). The hippocampus consists of several subfields that may
      be differentially related to MDD. We investigated the association of occurrence
      of major depressive episodes (MDEs), assessed five times over seven years, with
      hippocampal subfield and entorhinal cortex volumes at 7 tesla MRI. METHODS: In
      this prospective study of randomly selected general practice attendees, MDEs
      according to DSM-IV-R criteria were assessed at baseline and after 6, 12, 39 and
      84 months follow-up. At the last follow-up, a T2 (0.7 mm(3)) 7 tesla MRI scan was
      obtained in 47 participants (60+/-10 years). The subiculum, cornu ammonis (CA) 1
      to 3, dentate gyrus&CA4 and entorhinal cortex volumes were manually segmented
      according a published protocol. RESULTS: Of the 47 participants, 13 had one MDE
      and 5 had multiple MDEs. ANCOVAs, adjusted for age, sex, education and
      intracranial volume, revealed no significant differences in hippocampal subfield
      or entorhinal cortex volumes between participants with and without an MDE in the
      preceding 84 months. Multiple episodes were associated with smaller subiculum
      volumes (B=-0.03 mL/episode; 95% CI -0.06; -0.003), but not with the other
      hippocampal subfield volumes, entorhinal cortex, or total hippocampal volume.
      LIMITATIONS: A limitation of this study is the small sample size which makes
      replication necessary. CONCLUSIONS: In this exploratory study, we found that an
      increasing number of major depressive episodes was associated with smaller
      subiculum volumes in middle-aged and older persons, but not with smaller volumes
      in other hippocampal subfields or the entorhinal cortex.

PMID- 25589379
TI  - New BPD predicts lung function at school age: Follow-up study and meta-analysis.
AB  - New treatment practices have improved survival of preterm infants and decreased
      airway pathology in bronchopulmonary dysplasia (BPD). Our aim was to investigate
      whether preterm birth, BPD, and the severity of BPD predict lung function in
      school children that are born in surfactant era. We studied pulmonary function of
      88 school-aged children born very preterm (gestational age <32 weeks) and paired
      them with 88 age- and sex-matched controls born at term. Spirometry and diffusion
      capacity were recorded. We also performed a meta-analysis covering the era of
      antenatal corticosteroid and surfactant treatment. BPD was defined as oxygen
      dependence for >= 28 days and it was severity-graded by oxygen requirement at 36
      weeks postmenstrual age (mild, none; moderate, FiO2 = 0.22-0.29; severe, FiO2 >=
      0.30). Preterm children had lower forced expiratory volume in 1 sec (FEV1 ) 86.4
      +/- 11.8 versus 94.9 +/- 10.1 (mean % predicted +/- SD; P < 0.001), and lower
      diffusion capacity (DLCO) 87.6 +/- 13.9 versus 93.7 +/- 12.0 (P = 0.005) compared
      with term controls. BPD group differed in both FEV1 (P = 0.037) and DLCO (P =
      0.018) from those without BPD. For meta-analysis, search identified 210 articles.
      Together with present results, six articles met the inclusion criteria. FEV1 of
      no BPD, all BPD, and moderate to severe BPD groups differed from that in term
      controls by -7.4, -10.5, and -17.8%, respectively. According to meta-analysis and
      follow-up study, the adverse effects of prematurity on pulmonary function are
      still detectable in school-age. BPD was associated with reductions in both
      diffusion capacity and spirometry. New interventions are required to document a
      further decrease in the life-long consequences of prematurity.

PMID- 25589382
TI  - Fullerene-ionic-liquid conjugates: a new class of hybrid materials with
      unprecedented properties.
AB  - A modular approach has been followed for the synthesis of a series of fullerene
      ionic-liquid (IL) hybrids in which the number of IL moieties (two or twelve),
      anion, and cation have been varied. The combination of C60 and IL give rise to
      new unique properties in the conjugates such as solubility in water, which was
      higher than 800 mg mL(-1) in several cases. In addition, one of the C60 -IL
      hybrids has been employed for the immobilization of palladium nanoparticles
      through ion exchange followed by reduction with sodium borohydride. Surprisingly,
      during the reduction several carbon nanostructures were formed that comprised
      nano-onions and nanocages with few-layer graphene sidewalls, which have been
      characterized by means of thermogravimetric analysis (TGA), X-ray photoelectron
      spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy/energy
      dispersive X-ray analysis (SEM-EDAX), and high-resolution transmission electron
      microscopy (HRTEM). Finally, the material thus obtained was successfully applied
      as catalyst in Suzuki and Mizoroki-Heck reactions in a concentration of just 0.2
      mol %. In the former process it was recyclable for five runs with no loss in
      activity.

PMID- 25589381
TI  - Supplanting ecosystem services provided by scavengers raises greenhouse gas
      emissions.
AB  - Global warming due to human-induced increments in atmospheric concentrations of
      greenhouse gases (GHG) is one of the most debated topics among environmentalists
      and politicians worldwide. In this paper we assess a novel source of GHG
      emissions emerged following a controversial policy decision. After the outbreak
      of bovine spongiform encephalopathy in Europe, the sanitary regulation required
      that livestock carcasses were collected from farms and transformed or destroyed
      in authorised plants, contradicting not only the obligations of member states to
      conserve scavenger species but also generating unprecedented GHG emission.
      However, how much of this emission could be prevented in the return to
      traditional and natural scenario in which scavengers freely remove livestock
      carcasses is largely unknown. Here we show that, in Spain (home of 95% of
      European vultures), supplanting the natural removal of dead extensive livestock
      by scavengers with carcass collection and transport to intermediate and
      processing plants meant the emission of 77,344 metric tons of CO2 eq. to the
      atmosphere per year, in addition to annual payments of ca. $50 million to
      insurance companies. Thus, replacing the ecosystem services provided by
      scavengers has not only conservation costs, but also important and unnecessary
      environmental and economic costs. 

PMID- 25589380
TI  - Novel interventions to prevent HIV and HCV among persons who inject drugs.
AB  - Persons who inject drugs (PWID) are at high risk for infection with and poor
      outcomes from HIV and hepatitis C virus (HCV). Well-established interventions for
      HIV/HCV prevention among PWID include syringe access, opioid agonist maintenance
      treatment, and supervised injection facilities, yet these interventions remain
      unavailable or inadequately resourced in much of the world. We review recent
      literature on biomedical and behavioral interventions to reduce the burden of
      HIV/HCV among PWID, with an emphasis on randomized controlled trials and quasi
      experimental studies. Since 2013, there have been significant advancements in
      utilizing antiviral therapy and behavioral interventions for prevention among
      PWID, including approaches that address the unique needs of couples and sex
      workers. In addition, there have been significant developments in
      pharmacotherapies for substance use and the implementation of naloxone for opioid
      overdose prevention. Notwithstanding multiple ongoing structural challenges in
      delivering HIV/HCV prevention interventions to PWID, these emerging and
      rigorously evaluated interventions expand possibilities for prevention among
      PWID. 

PMID- 25589384
TI  - Immunotherapy of melanoma: present options and future promises.
AB  - Metastatic melanoma is notorious for its immune evasion and resistance to
      conventional chemotherapy. The recent success of ipilimumab, a human monoclonal
      antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), in
      increasing the median survival time and stabilizing the disease progression
      renewed, hopes in treatment for melanoma. Currently, ipilimumab and high-dose
      interleukin-2 (IL-2; Aldesleukin) are approved as monotherapies for the treatment
      of patients with unresectable advanced melanoma, and pegylated interferon-alpha2b
      (p-IFN-alpha2b) is approved as an adjuvant for the treatment of patients with
      surgically resected high-risk melanoma. The present review describes the
      currently approved immune-modulators and the promising immune-based interventions
      that are currently in clinical trials. We present the four commonly used
      strategies to boost immune responses against the tumors; monoclonal antibodies,
      cytokines, cancer vaccines, and adoptive T cell transfer. The corresponding lists
      of ongoing clinical trials include details of the trial phase, target patients,
      intervention details, status of the study, and expected date of completion.
      Further, our review discusses the challenges faced by immunotherapy and the
      various strategies adopted to overcome them. 

PMID- 25589383
TI  - Determination of N-acetylglucosamine in cosmetic formulations and skin test
      samples by hydrophilic interaction liquid chromatography and UV detection.
AB  - N-Acetylglucosamine is an ingredient in pharmaceuticals, nutritional supplements
      and in cosmetics. N-Acetylglucosamine in cosmetics is expected to improve skin
      hydration, reparation, and to contribute as anti-wrinkle agent. This study
      reports on the validation and application of an HPLC method based on HILIC and UV
      detection for determining N-acetylglucosamine in cosmetics and in samples
      obtained after testing the skin exposed to cosmetics formulations. The
      chromatographic column used is a ZIC((r))-pHILIC (150 mm * 4.6 mm, 5 MUm particle
      size) on which a mobile phase containing acetonitrile-aqueous KH2PO4 (70:30, v/v)
      15 mM was applied in isocratic elution mode injecting 20 MUl of sample at 0.5
      ml/min constant flow-rate and 10+/-1 degrees C column temperature. Under these
      conditions the total run time was 10 min and N-acetylglucosamine eluted baseline
      separated from all other compounds in the samples. Calibration in the range from
      40 to 80 MUg/ml allowed to assess the method linearity (R(2)>0.999) in a
      concentration range corresponding to about 50% to 120% of the expected levels of
      N-acetylglucosamine in the formulations. Precision expressed by RSD% was always
      better than 2% in intra-day and inter-day assays of authentic samples. Accuracy
      was in all cases within 95-105% of the expected concentration value in
      formulations containing N-acetylglucosamine. The sensitivity of the method was at
      the level of 10 MUg/ml as limit of detection, and at 40 MUg/ml as limit of
      quantitation. The application of the method to formulations containing solid
      lipid nanoparticles documents its usefulness in cosmetic quality control. The
      results witness that the method is also suitable for the determination of N
      acetylglucosamine in samples obtained from skin test strips.

PMID- 25589385
TI  - Quantitative MRI T2 relaxation time evaluation of knee cartilage: comparison of
      meniscus-intact and -injured knees after anterior cruciate ligament
      reconstruction.
AB  - BACKGROUND: Associated meniscal injury is well recognized at anterior cruciate
      ligament (ACL) reconstruction, and it is a known risk factor for osteoarthritis.
      PURPOSE: To evaluate and characterize the postoperative appearance of articular
      cartilage after different meniscal treatment in ACL-reconstructed knees using T2
      relaxation time evaluation on MRI. STUDY DESIGN: Cohort study; Level of evidence,
      3. METHODS: A total of 62 consecutive patients who under ACL reconstruction were
      recruited in this study, including 23 patients undergoing partial meniscectomy
      (MS group), 21 patients undergoing meniscal repair (MR group), and 18 patients
      with intact menisci (MI group) at time of surgery. Clinical evaluation, including
      subjective functional scores and physical examination, was performed on the same
      day as the MRI examination and at follow-up times ranging from 2 to 4.2 years.
      The MRI multiecho sagittal images were segmented to determine the T2 relaxation
      time value of each meniscus and articular cartilage plate. Differences in each
      measurement were compared among groups. RESULTS: No patient had joint-line
      tenderness or reported pain or clicking on McMurray test or instability. There
      were also no statistically significant differences in functional scores or medial
      or lateral meniscus T2 values among the 3 groups (P > .05 for both). There was a
      significantly higher articular cartilage T2 value in the medial femorotibial
      articular cartilage for the MS group (P < .01) and the MR group (P < .05)
      compared with that of the MI group, while there was no significant difference in
      articular cartilage T2 value between the MS and MR groups (P > .05) in each
      articular cartilage plate. The medial tibial articular cartilage T2 value had a
      significant positive correlation with medial meniscus T2 value (r = 0.287; P =
      .024) CONCLUSION: This study demonstrates that knees with meniscectomy or
      meniscal repair had articular cartilage degeneration at 2 to 4 years
      postoperatively, with higher articular cartilage T2 relaxation time values
      compared with the knees with an intact meniscus.

PMID- 25589386
TI  - Effect of lateral meniscal root tear on the stability of the anterior cruciate
      ligament-deficient knee.
AB  - BACKGROUND: Meniscal root tears are an increasingly recognized subset of meniscal
      injury. The menisci are critical secondary stabilizers of the anterior cruciate
      ligament (ACL). The kinematic effect of lateral meniscus posterior root tear in
      the setting of ACL injury is not known. PURPOSE/HYPOTHESIS: The purpose of this
      study was to determine the effect of tear of the lateral meniscal root on
      stability of the ACL-deficient knee. The hypothesis was that disruption of the
      lateral meniscal root will further destabilize the ACL-deficient knee during a
      simulated pivot shift. STUDY DESIGN: Controlled laboratory study. METHODS: Pivot
      shift testing of 8 fresh-frozen cadaveric knees was performed after attachment of
      photoreflective flags and preparation of CT scans. Each knee was mounted in a
      custom activity simulator and dynamically loaded from 15 degrees  to 90 degrees 
      of flexion with all the permutations of the following: iliotibial band force (50,
      75, 100, 125, 150, and 175 N), internal rotation moments (1, 2, and 3 N.m), and
      valgus moments (5 and 7 N.m). In addition, anterior stability tests were
      performed by applying a 90-N anterior force to the tibia at flexion angles of 15
      degrees , 30 degrees , 45 degrees , 60 degrees , and 90 degrees . During each
      test, the anterior tibial translation and rotation of the tibia were measured
      with a high-resolution multiple infrared camera motion analysis system for the
      following 3 conditions: ACL-intact (ACL-I), ACL-deficient (ACL-D), and ACL
      deficient/lateral meniscal posterior root avulsion (ACL-D/LMR-A). RESULTS: A
      pivot-shift phenomenon was observed in the ACL-D and ACL-D/LMR-A conditions. The
      mean tibial translation of the lateral tibial condyle during the pivot-shift
      maneuver was 2.62 +/- 0.53 mm for the ACL-I knees, 6.01 +/- 0.51 mm for the ACL-D
      knees (P value vs. intact: .0005), and 8.13 +/- 0.75 mm for the ACL-D/LMR-A knees
      (P value vs intact: <.0001). During the pivot-shift maneuver, translation was
      significantly increased in the ACL-D/LMR-A condition compared with the ACL-D
      condition (P = .0146). Compared with the intact group, anterior tibial
      translation during the Lachman maneuver also increased at 30 degrees  and 90
      degrees  of flexion in the ACL-D group (P < .0001) and the ACL-D/LM group (P <
      .0001). No statistically significant difference was found between the ACL-D and
      ACL-D/LMR-A groups during the Lachman maneuver at 30 degrees  and 90 degrees  (P
      = .16 and .72, respectively). CONCLUSION: A tear of the lateral meniscal
      posterior root further reduces the stability of the ACL-deficient knee during
      rotational loading. CLINICAL RELEVANCE: This study shows that lateral meniscal
      root injury further destabilizes the ACL-deficient knee and thus advances the
      concept that the lateral meniscus is a secondary stabilizer of the knee under
      pivot-shift loading. In the absence of stronger evidence, the study data suggest
      a rationale for surgical repair of lateral meniscal root tears encountered in the
      setting of ACL tears.

PMID- 25589387
TI  - Conformational preferences of 3,4-dihydroxyphenylacetic acid (DOPAC).
AB  - The conformational space of 3,4-dihydroxyphenylacetic acid (DOPAC), an important
      dopamine metabolite, has been investigated by quantum chemical methods (B3LYP and
      MP2, with the 6-311++G(d,p) basis set) and matrix-isolation infrared
      spectroscopy. Detailed analysis of the calculated potential energy surfaces of
      the molecule led to identification of thirteen unique conformers, all of them
      showing the acetic acid side chain out of the aromatic ring plane by 60-95
      degrees . According to the calculated Gibbs energies, the five lowest energy
      conformers make up 99.7% of the conformational mixture at 298.15K, exhibiting
      individual populations falling between 16% and 24%. The main conformational
      trends of this molecule were interpreted on the grounds of a thorough analysis of
      the structural parameters and by the application of the Natural Bond Orbital
      theory. The role of the intramolecular interactions on the relative stability and
      structure of the conformers was also investigated. The infrared spectrum of DOPAC
      was registered after isolation of its monomers in argon and xenon matrices. Only
      one of DOPAC forms populated in the gas phase could be trapped in both matrix
      gases. This result is in agreement with the predicted low energy barriers for
      conformational isomerization and is also supported by annealing experiments. The
      spectra of matrix-isolated model compounds, phenylacetic acid and catechol, were
      studied under the same experimental conditions. These data were used as
      references and assisted in the interpretation of the results obtained for DOPAC. 

PMID- 25589388
TI  - Spectroscopic studies and quantum chemical investigations of (3,4
      dimethoxybenzylidene) propanedinitrile.
AB  - The Fourier Transform Infrared (FTIR), Ultra-Violet Visible (UV-Vis) spectroscopy
      and Thermogravimetric (TG) analysis of (3,4-dimethoxybenzylidene)
      propanedinitrile have been carried out and investigated using quantum chemical
      calculations. The molecular geometry, harmonic vibrational frequencies, Mulliken
      charges, natural atomic charges and thermodynamic properties in the ground state
      have been investigated by using Hartree Fock Theory (HF) and Density Functional
      Theory (DFT) using B3LYP functional with 6-311G(d,p) basis set. Both HF and DFT
      methods yield good agreement with the experimental data. Vibrational modes are
      assigned with the help of Vibrational Energy Distribution Analysis (VEDA)
      program. UV-Visible spectrum was recorded in the spectral range of 190-800nm and
      the results are compared with the calculated values using TD-DFT approach.
      Stability of the molecule arising from hyperconjugative interactions, charge
      delocalization have been analyzed using natural bond orbital (NBO) analysis. The
      results obtained from the studies of Highest Occupied Molecular Orbital (HOMO)
      and Lowest Unoccupied Molecular Orbital (LUMO) are used to calculate molecular
      parameters like ionization potential, electron affinity, global hardness,
      electron chemical potential and global electrophilicity. 

PMID- 25589389
TI  - Reactivity and molecular modeling of new solvatochromic mixed-ligand copper(II)
      chelates of 2-acetylbutyrolactone and dinitrogen bases.
AB  - A new series of solvatochromic mononuclear mixed ligand chelates with the general
      formula: Cu(AcBL)(L)X; where AcBL=2-acetylbutyrolactonate, L=N,N,N',N'
      tetramethylethylenediamine (Me4en), N,N,N',N'-tetramethylpropylene diamine
      (Me4pn), 1,10-phenanthroline (Phen) or 2,2'-bipyridyl (Bipy) and X=ClO4-, NO3- or
      Br- have been synthesized and characterized by the analytical and spectral
      methods, as well as magnetic and molar conductance measurements. The d-d
      absorption bands of Me4en-chelates as Nujol mulls or weak donor solvents
      solutions revealed square-planar, distorted octahedral and/or distorted trigonal
      bipyramid geometries for the perchlorate, nitrate and bromide chelates,
      respectively. However, an octahedral structure is identified for chelates in
      strong donor solvents. Perchlorate chelates show a remarkable color change from
      violet to green as the Lewis basicity of the donor solvent increases, whereas
      bromide chelates are mainly affected by the Lewis acidity of solvent. Specific
      and non-specific interactions of solvent molecules with the chelates were
      investigated on the basis of unified solvation model. Structural parameters of
      the free ligands and their Cu(II)-chelates have been calculated on the basis of
      semiempirical PM3 level and correlated with the experimental data.

PMID- 25589390
TI  - Quantum chemical calculation (electronic and topologic) and experimental (FT-IR,
      FT-Raman and UV) analysis of isonicotinic acid N-oxide.
AB  - In this work, the molecular conformation, vibrational and electronic analysis of
      isonicotinic acid N-oxide (iso-NANO) were presented in the ground state using
      experimental techniques (FT-IR, FT-Raman and UV) and density functional theory
      (DFT) employing B3LYP exchange correlation with the 6-311++G(d,p) basis set. The
      geometry optimization and energies associated possible two conformers (Rot-I and
      Rot-II) were computed. The 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. The obtained structures were analyzed with the Atoms in Molecules
      (AIMs) methodology. The computational results diagnose the most stable conformer
      of iso-NANO as the Rot-I form. Total density of state (TDOS) and partial density
      of state (PDOS) and also overlap population density of state (OPDOS) diagrams
      analysis for the most stable conformer (Rot-I) were calculated using the same
      method. Thermodynamic properties (heat capacity, entropy and enthalpy) of the
      title compound at different temperatures were calculated. As a result, the
      optimized geometry and calculated spectroscopic data show a good agreement with
      the experimental results. 

PMID- 25589391
TI  - Infra-red spectroscopic characteristics of naphthalocyanine in
      bis(naphthalocyaninato) rare earth complexes peripherally substituted with
      thiophenyl derivatives.
AB  - The infra-red (IR) spectroscopic data for a series of eleven rare earth double
      deckers MIII[Nc(SPh)8]2 (M=Y, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho and Er) have
      been collected and systematically investigated. For MIII[Nc(SPh)8]2, typical IR
      marker bands for the naphthalocyanine anion radical [Nc(SPh)8].- were observed at
      1317-1325 cm(-1) as the most intense absorption bands, which can be attributed to
      the pyrrole stretching. As for Ce[Nc(SPh)8]2, the typical IR marker band was also
      observed at 1317 cm(-1), which shows that the cerium complex exists as the form
      of CeIII[Nc(SPh)8]2-[Nc(SPh)8].-. In addition, both the Q-bands of electronic
      absorption spectra and the typical IR absorption bands of naphthalocyanine
      radical anion [Nc(SPh)8].- move to the high energy as the decrease of rare earth
      metal ionic radius. These facts suggest that the pi-pi electron interaction in
      these double-deckers becomes stronger along with the lanthanide contraction.

PMID- 25589392
TI  - Temperature-related degradation and colour changes of historic paintings
      containing vivianite.
AB  - Temperature-related degradation of pure synthetic as well as partly oxidised
      natural vivianite has been studied by high-temperature X-ray diffraction (HT-XRD)
      covering the whole extent of the temperature-related stability of its structure.
      While temperatures around 70 degrees C are already damaging to vivianite,
      exposition to 160 degrees C results in complete amorphisation of both the
      vivianite and its oxidation products. As indicated by Mossbauer spectroscopy,
      temperature-induced oxidation of vivianite starts at 90 degrees C. To study the
      occurring structural as well as accompanying colour changes in more detail, model
      vivianite paint layer samples with different historic binders were prepared and
      subjected to increased temperatures. Exposition to 80 degrees C caused pronounced
      colour changes of all the samples: ground natural blue vivianite became grey--a
      colour change which has been described in actual works of art. Regarding the
      binders, the oil seemed to facilitate the transfer of heat to vivianite's grains.
      To simulate conditions of conservation treatment under which the painting is
      exposed to increased temperatures, oil-on-canvas mock-ups with vivianite were
      prepared and relined in a traditional way using iron. The treatment affected
      preferentially larger grains of vivianite; the micro-samples documented their
      change to grey, and their Raman spectra showed the change from vivianite to
      metavivianite.

PMID- 25589393
TI  - Polymer complexes. LX. Supramolecular coordination and structures of N(4
      (acrylamido)-2-hydroxybenzoic acid) polymer complexes.
AB  - A number of novel polymer complexes of various anions of copper(II), cobalt(II),
      nickel(II) and uranyl(II) with N(4-(acrylamido)-2-hydroxy benzoic acid) (ABH)
      have been synthesized and characterized by elemental analysis, IR, 1H NMR,
      magnetic susceptibility measurements, electronic spin resonance, vibrational
      spectra and thermal analysis. The molecular structures of the ligand are
      optimized theoretically and the quantum chemical parameters are calculated.
      Tentative structures for the polymeric metal complexes due to their potential
      application are also suggested. The IR data exhibit the coordination of
      ONO2/OAc/SO4 with the metal ions in the polymeric metal complex. Vibrational
      spectra indicate coordination of carboxylate oxygen and phenolic OH of the ligand
      giving a MO4 square planar chromophore. Ligand field ESR spectra support square
      planar geometry around Cu(II). The thermal decomposition of the polymer complexes
      were discussed in relation to structure, and the thermodynamic parameters of the
      decomposition stages were evaluated applying Coast-Redfern and Horowitz-Metzger
      methods.

PMID- 25589394
TI  - Application of spectroscopic methods for identification (FT-IR, Raman
      spectroscopy) and determination (UV, EPR) of quercetin-3-O-rutinoside.
      Experimental and DFT based approach.
AB  - Vibrational (FT-IR, Raman) and electronic (UV, EPR) spectral measurements were
      performed for an analysis of rutin (quercetin-3-O-rutinoside) obtained from
      Rutaofficinalis. The identification of rutin was done with the use of FT-IR and
      Raman spectra. Those experimental spectra were determined with the support of
      theoretical calculations based on a DFT method with the B3LYP hybrid functional
      and 6-31G(d,p) basis set. The application of UV and EPR spectra was found to be a
      suitable analytical approach to the evaluation of changes in rutin exposed to
      certain physicochemical factors. Differences in absorbance observed in direct UV
      spectra were used to monitor changes in the concentration of rutin in degraded
      samples. Spectra of electron paramagnetic resonance allowed studying the process
      of free-radical quenching in rutin following its exposure to light. The molecular
      electrostatic potential (MEP) and frontier molecular orbitals (LUMO-HOMO) were
      also determined in order to predict structural changes and reactive sites in
      rutin. 

PMID- 25589395
TI  - beta-Hydroxy-alpha-naphthaldehyde [2-(quinolin-8'-yloxy) acetyl] hydrazone as an
      efficient fluorescent chemosensor for Mg2+.
AB  - An efficient fluorescent sensor based on beta-hydroxy-alpha-naphthaldehyde [2
      (quinolin-8'-yloxy) acetyl] hydrazone (HL) for Mg2+ has been designed and
      synthesized. The receptor showed "off-on" fluorescent responses toward Mg2+ in
      acetonitrile. The reasons for this phenomenon is that the addition of Mg2+ to the
      solution of HL induce the formation of a 1:1 ligand-metal complex which inhibit
      excited-state intramolecular proton transfer (ESIPT).

PMID- 25589396
TI  - Investigation on growth, structure and characterization of succinate salt of 8
      hydroxyquinoline: an organic NLO crystal.
AB  - 8-Hydroxyquinolinium succinate (8-HQSU) has been synthesized and single crystals
      were grown from ethanol solvent by employing the technique of slow evaporation at
      room temperature. The structure of the grown crystal has been elucidated by
      single crystal X-ray diffraction analysis. It reveals that 8-HQSU crystallizes in
      monoclinic system with non-centro symmetric space group P2(1). FTIR, 1H and 13C
      NMR spectral investigations have been carried out to identify the vibrational
      modes of various functional groups and placement of proton and carbon in the 8
      HQSU compound, respectively. UV-vis-NIR transmission spectrum shows the cutoff
      wavelength around 357 nm. In addition, a photoluminescence spectral analysis was
      carried out for 8-HQSU crystals. The thermal properties of crystals were
      evaluated from TGA and DTA techniques and the crystal was found to be stable up
      to 145 degrees C. The dielectric studies show that the dielectric constant and
      dielectric loss decrease exponentially with frequency at different temperatures.
      Photoconductivity studies were carried out on the grown crystals it reveals the
      positive photo conducting nature. Powder second harmonic generation property of
      the crystal was confirmed by Kurtz and Perry powder SHG technique and it is found
      to be 1.3 times greater than that of KDP.

PMID- 25589398
TI  - Recurrent pregnancy loss and obesity.
AB  - Recurrent pregnancy loss (RPL) was defined as two or more miscarriages.
      Antiphospholipid syndrome, uterine anomalies, and parental chromosomal
      abnormalities, particularly translocation and abnormal embryonic karyotype, are
      identifiable causes of RPL. Obesity may increase the risk of sporadic miscarriage
      in pregnancies conceived spontaneously. Obesity with body mass index (BMI)>30
      kg/m2 is an independent risk factor for further miscarriage with odds ratio 1.7
      3.5 in patients with early RPL. Obesity is associated with euploid miscarriage.
      Unexplained RPL with euploid embryo might be a common disease caused by both
      polymorphisms of multiple susceptibility genes and lifestyle factors such as
      women's age, obesity, and smoking. Patients with a history of RPL were found to
      have a higher risk of cardiovascular disease, celiac disease, gastric ulcer,
      gastritis, and atopic dermatitis. No study has examined the effect of weight loss
      on the prevention of further miscarriage in patients with RPL.

PMID- 25589397
TI  - Mutations in Bruton's tyrosine kinase impair IgA responses.
AB  - X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by
      mutations in Bruton's tyrosine kinase (BTK), and is characterized by markedly
      decreased numbers of blood B cells and an absence of all immunoglobulin isotypes.
      We performed whole exome sequencing in a male pediatric patient with
      dysgammaglobulinemia with IgA deficiency. Genetic analysis revealed a BTK
      missense mutation (Thr316Ala). To investigate whether a BTK mutation underlay
      this antibody deficiency with marked decrease of IgA in this patient, we
      performed functional analyses of B cells and phagocytes, and molecular analyses
      of somatic hypermutation and class switch recombination. The BTK missense
      mutation resulted in B cells with reduced BTK and high IgM expression. Equal
      proportions of CD19(low) and CD19(normal) fractions were observed, and both
      included naive and memory B cells. Calcium influx and phospholipase Cgamma2
      phosphorylation upon IgM stimulation were marginally impaired in CD19(low), but
      not in CD19(+) B cells. Similar to XLA patients, IgA transcripts showed low SHM
      levels, whereas IgG transcripts were hardly affected. Our analyses suggest that
      the BTK mutation likely underlies the disease in this case, and that hypomorphic
      BTK mutations can result in normal circulating B cell numbers, but specifically
      impair IgA responses. 

PMID- 25589399
TI  - Reviews: Rapid! Rapid! Rapid! ...and systematic.

PMID- 25589401
TI  - Erratum: Disease burden of pneumonia in Korean adults aged over 50 years
      stratified by age and underlying diseases.
AB  - [This corrects the article on p. 764 in vol. 29, PMID: 25378975.]. 

PMID- 25589403
TI  - Increasing Epilepsy Awareness in Schools: A Seizure Smart Schools Project.
AB  - A high prevalence of epilepsy diagnoses and seizure events among students was
      identified at a large Midwestern school district. In partnership with the
      Epilepsy Foundation of Minnesota (EFMN), a quality improvement project was
      conducted to provide education and resources to staff caring for school children
      with seizures. School nurses (N = 26) were trained as seizure management
      educators and instructed staff in 21 schools on seizure awareness and response.
      School nurses utilized new seizure management resources, a procedural guideline,
      and care plan updates. The majority of school nurses rated the resources and
      training interventions as "very helpful." School nurse confidence in managing
      students with seizures increased, seizure action plan use increased, and 88% of
      children's records with new seizure diagnoses had completed documentation. School
      nurses played vital roles in increasing seizure awareness as educators and care
      managers. EFMN is using this project as an exemplar for expanding its Seizure
      Smart Schools program. 

PMID- 25589402
TI  - Effect of silicone on the collagen fibrillogenesis and stability.
AB  - Collagen, the most abundant protein in mammals, is able to form fibrils, which
      have central role in tissue repair, fibrosis, and tumor invasion. As a component
      of skin, tendons, and cartilages, this protein contacts with any implanted
      materials. An inherent problem associated with implanted prostheses is their
      propensity to be coated with host proteins shortly after implantation. Also,
      silicone implants undergoing relatively long periods of contact with blood can
      lead to formation of thrombi and emboli. In this paper, we demonstrate the
      existence of interactions between siloxanes and collagen. Low-molecular-weight
      cyclic siloxane (hexamethylcyclotrisiloxane-D3) and polydimethylsiloxanes (PDMS)
      forming linear chains, ranging in viscosity from 20 to 12,000 cSt, were analyzed.
      We show that D3 as well as short-chain PDMS interact with collagen, resulting in
      a decrease in fibrillogenesis. However, loss of collagen native structure does
      not occur because of these interactions. Rather, collagen seems to be sequestered
      in its native form in an interlayer formed by collagen-siloxane complexes. On the
      other hand, silicone molecules with longer chains (i.e., PDMS with viscosity of
      1000 and 12,000 cSt, the highest viscosity analyzed here) demonstrate little
      interaction with this protein and do not seem to affect collagen activity.

PMID- 25589405
TI  - In reply to "impact of the psychiatry clerkship on medical student attitudes
      towards psychiatry and to psychiatry as a career".

PMID- 25589404
TI  - Remobilizing deleted piggyBac vector post-integration for transgene stability in
      silkworm.
AB  - Deletion of transposable elements post-genomic integration holds great promise
      for stability of the transgene in the host genome and has an essential role for
      the practical application of transgenic animals. In this study, a modified
      piggyBac vector that mediated deletion of the transposon sequence post
      integration for transgene stability in the economically important silkworm Bombyx
      mori was constructed. The piggyBac vector architecture contains inversed terminal
      repeat sequences L1, L2 and R1, which can form L1/R1 and L2/R1 types of
      transposition cassettes. hsp70-PIG as the piggyBac transposase expression
      cassette for initial transposition, further remobilization and transgene
      stabilization test was transiently expressed in a helper vector or integrated
      into the modified vector to produce a transgenic silkworm. Shortening L2
      increased the transformation frequency of L1/R1 into the silkworm genome compared
      to L2/R1. After the integration of L1/R1 into the genome, the remobilization of
      L2/R1 impaired the transposon structure and the resulting transgene linked with
      an impaired transposon was stable in the genome even in the presence of
      exogenously introduced transposase, whereas those flanked by the intact
      transposon were highly mobile in the genome. Our results demonstrated the
      feasibility of post-integration deletion of transposable elements to guarantee
      true transgene stabilization in silkworm. We suggest that the modified vector
      will be a useful resource for studies of transgenic silkworms and other piggyBac
      transformed organisms. 

PMID- 25589406
TI  - "I started to feel like a 'real doctor'": medical students' reflections on their
      psychiatry clerkship.
AB  - OBJECTIVE: Medical students' reflective journals can be a rich source for
      understanding what students learn and think about during clinical rotations and
      can offer educators and mentors insight into students' professional identity
      formation. The aim of this paper is to ascertain, from reflective accounts,
      students' development and reactions to psychiatry following their psychiatry
      clerkship. METHOD: The patterns, recurrent categories, and themes in 100
      psychiatry clerks' reflective journals were analyzed using grounded theory.
      Constant comparative method was employed to identify and quantify emergent themes
      and uncover relationships between these themes. RESULTS: The most common
      "unprompted" themes that students reported were the recognition of the complexity
      of the illness condition and the fact that the psychiatric patient does not exist
      in a vacuum (52 %); an acknowledgement of one's respect for the struggle of
      patients with mental illness (49 %); an expressed or demonstrated empathy for
      patients (48 %); and a reduced skepticism of the biological basis of mental
      illness and efficacy of treatments (46 %). CONCLUSION: Reflective exercises-along
      with quality mentorship-can be used to understand students' experience with
      clinical encounters, facilitate change, refine assumptions among students, and
      promote critical self-assessment and personal growth.

PMID- 25589407
TI  - Labour Market Status and Well-Being in the Context of Return to Work After
      Vocational Rehabilitation in Germany.
AB  - INTRODUCTION: Although there is much empirical evidence for a given relationship
      between health and labour market status (LMS), the following study focuses on a
      group for which little is known in the German context: people with disabilities
      in vocational rehabilitation for the purpose of re-integration into the labour
      market. In this specific context, the article analyses how a change in LMS
      affects physical, mental and general health. METHODS: Using a panel survey, 857
      people with disabilities in vocational rehabilitation and their subjective health
      condition were observed between 2008 and 2010. To reduce bias due to unobserved
      heterogeneity, fixed-effects panel regression is applied. RESULTS: Results show
      that a move from non-employment to employment positively affects-particularly
      general-subjective health. In addition to LMS, the level of occupational
      limitation due to disability appears to be of particular relevance in estimating
      health. Interacting both the level of occupational limitation and LMS reveals
      that non-employed people reporting serious occupational limitation due to their
      disability have the worst subjective health across all aspects. However, people
      in employment experiencing similarly serious limitations due to their disability
      do not differ much from this group. These may be regarded as having taken up
      disability-inappropriate employment. CONCLUSION: The results suggest that re
      integration into employment particularly improves several health aspects if
      rehabilitants are integrated in an occupational environment where disability does
      not present an occupational limitation. Thus, placement in disability-appropriate
      employment needs to be particularly encouraged.

PMID- 25589409
TI  - Novel ALD-assisted growth of ZnO nanorods on graphene and its Cu2ZnSn(S(x)Se(1
      x))4 solar cell application.
AB  - The hydrothermal growth of ZnO nanorods on graphene draws a specific interest for
      the advantages of low-temperature processability over a large area and low cost,
      but challenges still remain in directly growing uniform ZnO seed layers on
      pristine graphene without impairing its beneficial properties. In this work, the
      direct growth of ZnO seed layers on graphene via H2O-based atomic layer
      deposition (ALD) has been investigated. It is found that uniform ZnO thin films
      can be deposited on graphene via ALD using a combination of single-layer
      graphene/Cu stacks as substrates and a facile pre-H2O treatment process. After
      growing ZnO nanorods on graphene, its photovoltaic application in a Cu2ZnSn(SxSe1
      x)4 (CZTSSe) solar cell is demonstrated. The performance of graphene-based cells
      approaches that of ITO-based cells with similar architectures, highlighting that
      graphene is a potential replacement for ITO in optoelectronic devices. The method
      reported herein for fabricating ZnO nanorods on graphene using ALD-ZnO as seed
      layers preserves its properties, and is thus applicable to a wide variety of
      graphene-based nanoelectronic devices. 

PMID- 25589410
TI  - The impact of social deprivation on coronary revascularisation treatment outcomes
      within the National Health Service in England and Wales.
AB  - BACKGROUND: There is strong evidence to suggest that social deprivation is linked
      to health inequalities. In the UK, concerns have been raised regarding
      disparities in the outcomes of acute cardiac services within the National Health
      Service (NHS). This study explored whether differences exist in (a) elective
      hospital presentation time (b) indicators of severity and disease burden and (c)
      treatment outcomes (hospital stay and mortality) on the basis of the index of
      multiple deprivation (IMD) status. DESIGN: This study was a retrospective
      analysis of data from NHS databases for 13,758 patients that had undergone
      cardiac revascularisation interventions at the Liverpool Heart and Chest Hospital
      between April 2007-March 2012. METHODS: The data was analysed by descriptive,
      univariate and multivariate statistics to explore the association between the IMD
      quintiles (Q1-Q5) and revascularisation type, elective presentation time,
      hospital length of stay and mortality. RESULTS AND CONCLUSIONS: Univariate
      analysis indicated that there were significant differences between patients from
      the most deprived areas (Q5) compared with patients from the least deprived areas
      (Q1), these included admission volumes, time before presentation to hospital and
      proportion of non-elective cases. After risk-adjustments, percutaneous coronary
      intervention patients from Q5 compared with Q1 had significantly greater length
      of hospital stay and risk of in-hospital major acute cardiovascular events. After
      multivariate adjustment for baseline risk factors, patients from Q5 were
      associated with significantly worse five-year survival as compared with Q1
      (hazard ratio (HR) 1.52, 95% confidence interval (CI): 1.36-1.71; p < 0.001). In
      conclusion, there is evidence to suggest that inequalities in cardiac
      revascularisation choices and outcomes in the UK may be associated with social
      deprivation.

PMID- 25589408
TI  - Methodological advances: the unsung heroes of the GPCR structural revolution.
AB  - G protein-coupled receptors (GPCRs) are intricately involved in a diverse array
      of physiological processes and pathophysiological conditions. They constitute the
      largest class of drug target in the human genome, which highlights the importance
      of understanding the molecular basis of their activation, downstream signalling
      and regulation. In the past few years, considerable progress has been made in our
      ability to visualize GPCRs and their signalling complexes at the structural
      level. This is due to a series of methodological developments, improvements in
      technology and the use of highly innovative approaches, such as protein
      engineering, new detergents, lipidic cubic phase-based crystallization and
      microfocus synchrotron beamlines. These advances suggest that an unprecedented
      amount of structural information will become available in the field of GPCR
      biology in the coming years. 

PMID- 25589411
TI  - Cofactor-independent antiphospholipid antibodies activate the NLRP3-inflammasome
      via endosomal NADPH-oxidase: implications for the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is an autoimmune disease characterised by
      thromboembolic events and/or pregnancy morbidity in the presence of
      antiphospholipid antibodies (aPL). Here we show that three cofactor independent
      human monoclonal aPL can induce transcription of NLRP3 and caspase-1 resulting in
      inflammasome activation specific for NLRP3. This depends fully on activation of
      endosomal NADPH-oxidase-2 (NOX2) by aPL. Activation of NOX2 and subsequent
      inflammasome activation by aPL are independent from TLR2 or TLR4. While endosomal
      superoxide production induces caspase-1 and NLRP3 transcription, it does not
      affect prae-IL-1beta transcription. Therefore, release of IL-1beta occurs only
      after activation of additional pathways like TLR7/8 or TLR2. All effects exerted
      by the monoclonal aPL can be reproduced with IgG fractions of APS patients
      proving that the monoclonal aPL are representative for the APS. IgG fractions of
      healthy controls or patients suffering from systemic lupus erythematosus have no
      effect. In a mouse model of the APS we can show inflammasome activation in vivo.
      Furthermore, mononuclear cells isolated from patients with the APS show an
      increased expression of caspase-1 and NLRP3 which is accompanied by a three-fold
      increased serum concentration of IL-1beta suggesting chronic inflammasome
      activation in APS patients. In summary, we provide further evidence that
      endosomal NOX2 can be activated by cofactor independent aPL. This leads to
      induction of the NLRP3 inflammasome. Our data indicate that cofactor independent
      aPL might contribute significantly to the pathogenesis of the APS.

PMID- 25589414
TI  - Transient anions of cis- and trans-cyclooctene studied by electron-impact
      spectroscopy.
AB  - The effect which deformation of the double bond in trans-cyclooctene (TCO),
      compared to cis-cyclooctene (CCO), has on its negative ion - and indirectly on
      the pi* virtual orbital - was studied by electron-impact spectroscopy.
      Differential elastic and vibrational excitation cross sections were measured at a
      scattering angle of theta = 135 degrees . The vertical attachment energy (VAE)
      derived from the vibrational excitation spectra is 1.87 eV in TCO, only 0.09 eV
      lower than in the unstrained CCO, 1.96 eV. The substantial deformation of the
      C[double bond, length as m-dash]C bond in TCO thus stabilizes its transient
      negative ion by a surprisingly small amount and this effect is ascribed in part
      to the Pauli (steric) destabilization of the TCO pi* orbital by the alkyl chain
      facing the pi* lobes. An interesting effect is observed in the elastic cross
      section which is about 45% larger for TCO at low energies (~0.4 eV), despite the
      similar geometrical size of the two molecules. Ramsauer-Townsend minima are
      observed in the elastic cross section at 0.13 and 0.12 eV for CCO and TCO,
      respectively. Implications of the findings on enhancement of the dienophile
      capacity of TCO are discussed. 

PMID- 25589412
TI  - Control of ethanol sensitivity of the glycine receptor alpha3 subunit by
      transmembrane 2, the intracellular splice cassette and C-terminal domains.
AB  - Previous studies have shown that the effect of ethanol onglycine receptors
      (GlyRs) containing the a1 subunit is affected by interaction with heterotrimeric
      G proteins (Gbetagamma). GlyRs containing the alpha3 subunit are involved in
      inflammatory pain sensitization and rhythmic breathing and have received much
      recent attention. For example, it is unknown whether ethanol affects the function
      of this important GlyR subtype. Electrophysiologic experiments showed that GlyR
      alpha3 subunits were not potentiated by pharmacologic concentrations of ethanol
      or by Gbetagamma. Thus, we studied GlyR alpha1-alpha3 chimeras and mutants to
      determine the molecular properties that confer ethanol insensitivity. Mutation of
      corresponding glycine 254 in transmembrane domain 2 (TM2) found in a1 in the
      alpha3(A254G) -alpha1 chimera induced a glycine-evoked current that displayed
      potentiation during application of ethanol (46 +/- 5%, 100 mM) and Gbetagamma
      activation (80 +/- 17%). Interestingly,insertion of the intracellular alpha3L
      splice cassette into GlyR alpha1 abolished the enhancement of the glycine
      activated current by ethanol (5 +/- 6%) and activation by Gbetagamma (21 6 7%).
      In corporation of the GlyR alpha1 C terminus into the ethanol-resistant
      alpha3S(A254G) mutant produced a construct that displayed potentiation of the
      glycine-activated current with 100 mM ethanol (40 +/- 6%)together with a current
      enhancement after G protein activation (68 +/- 25%). Taken together, these data
      demonstrate that GlyRalpha3 subunits are not modulated by ethanol. Residue A254
      in TM2, the alpha3L splice cassette, and the C-terminal domain of alpha3GlyRs are
      determinants for low ethanol sensitivity and form the molecular basis of subtype
      selective modulation of GlyRs by alcohol.

PMID- 25589415
TI  - Retinal vessel extraction using Lattice Neural Networks with Dendritic
      Processing.
AB  - Retinal images can be used to detect and follow up several important chronic
      diseases. The classification of retinal images requires an experienced
      ophthalmologist. This has been a bottleneck to implement routine screenings
      performed by general physicians. It has been proposed to create automated systems
      that can perform such task with little intervention from humans, with partial
      success. In this work, we report advances in such endeavor, by using a Lattice
      Neural Network with Dendritic Processing (LNNDP). We report results using several
      metrics, and compare against well known methods such as Support Vector Machines
      (SVM) and Multilayer Perceptrons (MLP). Our proposal shows better performance
      than other approaches reported in the literature. An additional advantage is that
      unlike those other tools, LNNDP requires no parameters, and it automatically
      constructs its structure to solve a particular problem. The proposed methodology
      requires four steps: (1) Pre-processing, (2) Feature computation, (3)
      Classification and (4) Post-processing. The Hotelling T(2) control chart was used
      to reduce the dimensionality of the feature vector, from 7 that were used before
      to 5 in this work. The experiments were run on images of DRIVE and STARE
      databases. The results show that on average, F1-Score is better in LNNDP,
      compared with SVM and MLP implementations. Same improvement is observed for MCC
      and the accuracy. 

PMID- 25589416
TI  - Tetracyclopenta[def,jkl,pqr,vwx]tetraphenylene: a potential tetraradicaloid
      hydrocarbon.
AB  - A tetramesityl derivative of hitherto unknown
      tetracyclopenta[def,jkl,pqr,vwx]tetraphenylene (TCPTP), which is a potential
      tetraradicaloid hydrocarbon, was synthesized. Theoretical calculations based on
      spin-flip time-dependent density functional theory predict that the closed-shell
      D2h form of TCPTP is more stable than the open-shell D4h form with its slightly
      tetraradical character. The tetramesityl derivative (Mes)4 -TCPTP exhibits
      remarkable antiaromaticity as a result of the peripheral 20-pi-electron circuit,
      which causes an absorption maximum at a long wavelength and a small HOMO-LUMO
      gap. In solution, (Mes)4 -TCPTP most likely adopts rapidly equilibrating D2h
      structures that interconvert via the D4h transition state. X-ray crystallographic
      analysis showed (Mes)4 -TCPTP as an approximate D2h structure. 

PMID- 25589413
TI  - The evolving role of nonsteroidal anti-inflammatory drugs in colon cancer
      prevention: a cause for optimism.
AB  - Colorectal cancer (CRC) is a serious yet preventable disease. The low acceptance
      and cost of colonoscopy as a screening method or CRC make chemoprevention an
      important option. Nonsteroidal anti-inflammatory drugs (NSAIDs), not currently
      recommended for CRC prevention, have the potential to evolve into the agents of
      choice for this indication. Here, we discuss the promise and challenge of NSAIDs
      for this chemopreventive application.Multiple epidemiologic studies, randomized
      clinical trials (RCTs) of sporadic colorectal polyp recurrence, RCTs in patients
      with hereditary colorectal cancer syndromes, and pooled analyses of
      cardiovascular-prevention RCTs linked to cancer outcomes have firmly established
      the ability of conventional NSAIDs to prevent CRC. NSAIDs, however, are seriously
      limited by their toxicity,which can become cumulative with their long-term
      administration for chemoprevention, whereas drug interactions in vulnerable
      elderly patients compound their safety. Newer, chemically modified NSAIDs offer
      the hope of enhanced efficacy and safety.Recent work also indicates that
      targeting earlier stages of colorectal carcinogenesis, such as the lower
      complexity aberrant crypt foci, is a promising approach that may only require
      relatively short use of chemopreventive agents. Drug combination approaches
      exemplified by sulindac plus difluoromethylornithine appear very efficacious.
      Identification of those at risk or most likely to benefit from a given
      intervention using predictive biomarkers may usher in personalized
      chemoprevention. Agents that offer simultaneous chemoprevention of diseases in
      addition to CRC, e.g., cardiovascular and/or neurodegenerative diseases,may have
      a much greater potential for a broad clinical application.

PMID- 25589418
TI  - Geographic variations in epidemiology of two autoimmune bullous diseases:
      pemphigus and bullous pemphigoid.
AB  - Autoimmune bullous diseases are rare, organ-specific, a group of blistering
      disease of skin and mucous membranes. Recent studies suggest that the frequency
      of the autoimmune bullous diseases has been increasing. Pemphigus vulgaris and
      bullous pemphigoid are the most frequently reported autoimmune bullous diseases.
      High incidence of autoimmune bullous diseases in some ethnic groups such as
      pemphigus in Ashkenazi Jewish, or in some regions such as pemphigus foliaceus in
      Brazil has been shown to be related to genetic and environmental factors,
      respectively. Pemphigus has been reported more frequently in the female gender.
      Although it is most frequently diagnosed between the ages 50 and 60 in European
      countries, in the remaining countries in the world, it is seen between the ages
      of 30 and 50. Bullous pemphigoid is generally seen above 70 years of age.
      Although overall incidence is slightly higher in females, after the age of 80
      years it is more frequent in males. Both pemphigus vulgaris and bullous
      pemphigoid has a chronic course with recurrences. Mortality risk of the patients
      with bullous pemphigoid was found at least 2 times higher and the mortality risk
      of the patients with pemphigus was found approximately 3 times higher than that
      of the general population. In this review, the results obtained from the
      epidemiological studies were analyzed according to geographic regions, and
      especially epidemiologic features of two prevalent autoimmune bullous diseases,
      pemphigus and bullous pemphigoid have been discussed.

PMID- 25589417
TI  - Molecular diversity of LysM carbohydrate-binding motifs in fungi.
AB  - LysM motifs are carbohydrate-binding modules found in prokaryotes and eukaryotes.
      They bind to N-acetylglucosamine-containing carbohydrates, such as chitin, chitio
      oligosaccharides and peptidoglycan. In this review, we summarize the features of
      the protein architecture of LysM-containing proteins in fungi and discuss their
      so far known biochemical properties, transcriptional profiles and biological
      functions. Further, based on data from evolutionary analyses and consensus
      pattern profiling of fungal LysM motifs, we show that they can be classified into
      a fungal-specific group and a fungal/bacterial group. This facilitates the
      classification and selection of further LysM proteins for detailed analyses and
      will contribute to widening our understanding of the functional spectrum of this
      protein family in fungi. Fungal LysM motifs are predominantly found in subgroup C
      chitinases and in LysM effector proteins, which are secreted proteins with LysM
      motifs but no catalytic domains. In enzymes, LysM motifs mediate the attachment
      to insoluble carbon sources. In plants, receptors containing LysM motifs are
      responsible for the perception of chitin-oligosaccharides and are involved in
      beneficial symbiotic interactions between plants and bacteria or fungi, as well
      as plant defence responses. In plant pathogenic fungi, LysM effector proteins
      have already been shown to have important functions in the dampening of host
      defence responses as well as protective functions of fungal hyphae against
      chitinases. However, the large number and diversity of proteins with LysM motifs
      that are being unravelled in fungal genome sequencing projects suggest that the
      functional repertoire of LysM effector proteins in fungi is only partially
      discovered so far. 

PMID- 25589419
TI  - The activation of cultured keratinocytes by cholesterol depletion during
      reconstruction of a human epidermis is reminiscent of monolayer cultures.
AB  - Transient cholesterol depletion from plasma membranes of human keratinocytes has
      been shown to reversibly activate signalling pathways in monolayer cultures.
      Consecutive changes in gene expression have been characterized in such conditions
      and were interestingly found to be similar to transcriptional changes observed in
      keratinocytes of atopic dermatitis (AD) patients. As an inflammatory skin
      disease, AD notably results in altered histology of the epidermis associated with
      a defective epidermal barrier. To further investigate whether the activation of
      keratinocytes obtained by cholesterol depletion could be responsible for some
      epidermal alterations reported in AD, this study was undertaken to analyse
      cholesterol depletion in stratified cultures of keratinocytes, i.e. a
      reconstructed human epidermis (RHE). RHE contains heterogeneous populations of
      keratinocytes, either proliferating or progressively differentiating and
      stratifying towards the creation of a cornified barrier. Cholesterol depletion
      induced in this model was found reversible and resulted in activation of
      signalling pathways similar to those previously identified in monolayers. In
      addition, selected changes in the expression of several genes suggested that
      keratinocytes in RHE respond to cholesterol depletion as monolayers. However,
      preserved histology and barrier function indicate that some additional
      activation, likely from the immune system, is required to obtain epidermal
      alterations such as the ones found in AD.

PMID- 25589420
TI  - [Cerebral MR imaging of malignant melanoma].
AB  - CLINICAL/METHODICAL ISSUE: Melanoma is the third leading cancer entity to
      metastasize to the central nervous system (CNS) after lung and breast cancer.
      This is often an early event in the disease course and limits survival.
      Metastasis in the CNS is the cause of death in 10-40 % of melanoma patients and
      the incidence of brain metastasis is even higher (50-75 %). Cerebral metastases
      are commonly found in the subcortical white matter. The signal characteristics
      can vary substantially and may change over time due to hemorrhages or the
      accumulation of melanin and paramagnetic ions. It is not yet clear whether novel
      targeted therapies (e.g. immunotherapy and kinase inhibitors) alter imaging
      characteristics. Also immune-related side effects, such as hypophysitis (in
      approximately 5 % of patients receiving ipilimumab therapy) or granulomatous
      disease (neurosarcoid) can occur. STANDARD RADIOLOGICAL METHODS: Melanoma
      metastases are usually hyperdense in computed tomography (CT). In magnetic
      resonance imaging (MRI) T2-weighted (T2-w) fluid-attentuated inversion recovery
      (FLAIR) and T1-w sequences (with and without i.v. contrast) should be obtained.
      Coronal and axial imaging planes should be scanned to cross-correlate findings.
      METHODICAL INNOVATIONS: Susceptibility-weighted imaging is a new sensitive method
      to detect melanoma metastases. Approximately 66 % of melanoma metastases show
      intratumoral susceptibility signals (ITSS). This sets them apart from other
      metastases (e.g. lung and breast cancer show less ITSSs, specificity
      approximately 81-96 %). Diffusion imaging plays no major role in melanoma brain
      imaging. PERFORMANCE: Susceptibility-weighted imaging increases the sensitivity
      to detect metastases but lacks specificity. Differentiating metastases,
      microbleeding or calcification can be impossible. It is controversial how to
      interpret susceptibility signals without correlative signs on other sequences
      (differential diagnosis: metastasis, microbleeding and calcification). PRACTICAL
      RECOMMENDATIONS: CNS metastases are common in melanoma. MRI screening starting in
      stage IIc should be considered even in asymptomatic patients. Stage IV requires
      quarterly MRI examinations. Melanotic and amelanotic metastases show different
      MRI characteristics. The differentiation between metastasis and microbleeding can
      be impossible and might require a follow-up scan. Susceptibility-weighted imaging
      increases the sensitivity of metastases detection but lacks specificity. It can
      help to differentiate between different metastatic entities.

PMID- 25589421
TI  - [Whole-body staging of malignant melanoma: advantages, limitations and current
      importance of PET-CT, whole-body MRI and PET-MRI].
AB  - Cross-sectional imaging methods are currently the standard methods for staging of
      advanced melanoma. The former time-consuming and expensive multimodality approach
      is increasingly being replaced by novel whole-body (WB) staging methods, such as
      18F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F
      FDG-PET-CT) and whole-body magnetic resonance imaging (WBMRI) because they offer
      a complete head-to-toe coverage of the patient in a single examination with an
      accurate and sensitive detection of tumor spread. Several studies in patients
      with advanced melanoma revealed that PET-CT is more sensitive and specific than
      conventional modalities, such as CT alone resulting in a change of management in
      up to 30 % of cases. Due to the limited sensitivity of PET for lesions smaller
      than 1 cm, PET-CT is not useful for the initial work-up of patients with stage I
      and II melanoma but has proven to be superior for detection of distant
      metastases, which is essential prior to surgical metastasectomy. If PET-CT is not
      available WB-CT or WB-MRI can alternatively be used and WB-MRI including
      diffusion-weighted imaging (DWI) has become a real alternative for staging of
      melanoma patients. So far, however, only few reports suffering from small numbers
      of cases and heterogeneous design have compared the diagnostic performance of WB
      MRI and PET-CT. The preliminary results indicate a high overall diagnostic
      accuracy of both methods; however, these methods differ in organ-based detection
      rates: PET-CT was more accurate in N-staging and detection of lung and soft
      tissue metastases whereas WB-MRI was superior in detecting liver, bone and brain
      metastases. The value of PET-MRI for staging of advanced melanoma is the subject
      of ongoing clinical studies.

PMID- 25589423
TI  - Continuous-flow sorting of stem cells and differentiation products based on
      dielectrophoresis.
AB  - This paper presents a continuous-flow microfluidic device for sorting stem cells
      and their differentiation progenies. The principle of the device is based on the
      accumulation of multiple dielectrophoresis (DEP) forces to deflect cells
      laterally in conjunction with the alternating on/off electric field to manipulate
      the cell trajectories. The microfluidic device containing a large array of
      oblique interdigitated electrodes was fabricated using a combination of standard
      and soft lithography techniques to generate a PDMS-gold electrode construct.
      Experimental testing with human mesenchymal stem cells (hMSC) and their
      differentiation progenies (osteoblasts) was carried out at different flow rates,
      and clear separation of the two populations was achieved. Most of the osteoblasts
      experiencing stronger DEP forces were deflected laterally and continuously,
      following zig-zag trajectories, and moved towards the desired collection outlet,
      whereas most of the hMSCs remained on the original trajectory due to weaker DEP
      forces. The experimental measurements were characterized and evaluated
      quantitatively, and consistent performance was demonstrated. Collection
      efficiency up to 92% and 67% for hMSCs and osteoblasts, respectively, along with
      purity up to 84% and 87% was obtained. The experimental results established the
      feasibility of our microfluidic DEP sorting device for continuous, label-free
      sorting of stem cells and their differentiation progenies. 

PMID- 25589422
TI  - Mass spectrometry-based plant metabolomics: Metabolite responses to abiotic
      stress.
AB  - Metabolomics is one omics approach that can be used to acquire comprehensive
      information on the composition of a metabolite pool to provide a functional
      screen of the cellular state. Studies of the plant metabolome include analysis of
      a wide range of chemical species with diverse physical properties, from ionic
      inorganic compounds to biochemically derived hydrophilic carbohydrates, organic
      and amino acids, and a range of hydrophobic lipid-related compounds. This
      complexitiy brings huge challenges to the analytical technologies employed in
      current plant metabolomics programs, and powerful analytical tools are required
      for the separation and characterization of this extremely high compound diversity
      present in biological sample matrices. The use of mass spectrometry (MS)-based
      analytical platforms to profile stress-responsive metabolites that allow some
      plants to adapt to adverse environmental conditions is fundamental in current
      plant biotechnology research programs for the understanding and development of
      stress-tolerant plants. In this review, we describe recent applications of
      metabolomics and emphasize its increasing application to study plant responses to
      environmental (stress-) factors, including drought, salt, low oxygen caused by
      waterlogging or flooding of the soil, temperature, light and oxidative stress (or
      a combination of them). Advances in understanding the global changes occurring in
      plant metabolism under specific abiotic stress conditions are fundamental to
      enhance plant fitness and increase stress tolerance. (c) 2015 Wiley Periodicals,
      Inc. Mass Spec Rev 35:620-649, 2016.

PMID- 25589424
TI  - Tension-free vaginal tape-obturator and tension-free vaginal tape-Secur for the
      treatment of stress urinary incontinence: a 5-year follow-up randomized study.
AB  - OBJECTIVE: Single-incision slings were developed to overcome the complications
      related to retropubic and trans-obturator tapes. TVT-Secur was the first of this
      kind of devices to be marketed and yielded contrasting results. Aim of this non
      inferiority study is to report the 5-year follow-up of a randomized, single
      blind, controlled trial comparing TVT-O to TVT-Secur. STUDY DESIGN: Randomized,
      single blind, controlled study conducted in two tertiary urogynecological
      centers. 154 patients were allocated to either TVT-O or TVT-Secur and were
      contacted 5 years after the procedure to undergo urogynecological examination
      (POP-Q staging, challenge stress test and post-void residual urine evaluation),
      to complete I-QOL and PGI-I questionnaires, and to score their satisfaction on a
      5-point Likert scale. Patients who were not objectively evaluated were
      interviewed over the telephone. Primary outcome was subjective success defined as
      being "very much improved" or "much improved" on the PGI-I. RESULTS: 120 patients
      were evaluated only subjectively (TVT-O: 62; TVT-Secur: 58) and 84 objectively
      and subjectively (TVT-O: 46; TVT-Secur: 38). Subjective success (79% vs. 63.8%)
      and objective cure rates (82.6% vs. 68.4%) 5 years after the procedure were lower
      for TVT-Secur, but not significantly. Recurrent UTIs were reported by 17.8% of
      women (TVT-O 9, TVT-Secur 6) and two de novo urgency cases (one per group) were
      observed. Re-operation rate for stress urinary incontinence (SUI) was 20%.
      CONCLUSIONS: TVT-Secur did not show an inferior subjective success rate in
      comparison with TVT-O five year after the original procedure, even though
      displaying a clear trend toward a lower efficacy. Considering that the long-term
      safety profile is similar between the two procedures, there are no advantages in
      using TVT-Secur.

PMID- 25589425
TI  - A secreted protein (Canopy 2, CNPY2) enhances angiogenesis and promotes smooth
      muscle cell migration and proliferation.
AB  - AIMS: Ischaemic heart disease is a leading cause of mortality. After ischaemic
      injury, tissue hypoxia induces the activity of angiogenic factors that promote
      revascularization. Increased understanding of hypoxia-responsive genes and their
      role in angiogenesis will lead to new therapies for ischaemic injury. We
      delineated the function of Canopy 2 (CNPY2), a newly discovered, hypoxia
      regulated gene. METHODS AND RESULTS: We found CNPY2 in a screen for genes induced
      by low oxygen in human smooth muscle cells (SMCs). CNPY2 protein co-localized
      with the endoplasmic reticulum and the Golgi. Treatment with Brefeldin A, which
      destroys Golgi stacks, resulted in CNPY2 accumulation in the endoplasmic
      reticulum. Secreted CNPY2 was detected in the blood of healthy mice and humans,
      and the medium of cultured SMCs. SMCs under hypoxia or treated with a prolyl-4
      hydroxylase inhibitor stabilized HIF-1alpha protein and up-regulated CNPY2, while
      CNPY2 induction was lost after HIF-1alpha silencing. Chromatin
      immunoprecipitation demonstrated that HIF-1alpha binds to a hypoxia response
      element (HRE-1157) upstream of the human CNPY2 promoter, which was verified by a
      luciferase reporter driven by HRE-1157-containing constructs. CNPY2 stimulation
      activated Cdc42, PAK1, and FAK in SMCs, resulting in enhanced proliferation and
      migration in vitro, and dramatic aortic ring sprouting ex vivo. CNPY2
      significantly increased revascularization of the mouse retina after reperfusion
      injury. CONCLUSIONS: CNPY2 is a HIF-1alpha-regulated, secreted angiogenic growth
      factor that promotes SMC migration, proliferation, and tissue revascularization.
      This new target may have a broader profile than currently available proteins.

PMID- 25589428
TI  - Piezo-phototronic UV/visible photosensing with optical-fiber-nanowire hybridized
      structures.
AB  - An optical-fiber-nanowire hybridized UV-visible photodetector (PD) is reported.
      The PD is designed to allow direct integration in optical communication systems
      without requiring the use of couplers via fiber-welding technology. The PD works
      in two modes: axial and off-axial illumination mode. By using the piezo
      phototronic effect, the performance of the PD is enhanced/optimized by up to 718%
      in sensitivity and 2067% in photoresponsivity. 

PMID- 25589427
TI  - Evaluation of the effects of chromium supplementation on growth and nitrogen
      balance of camel calves under summer conditions.
AB  - One of the most important problems in the production of camels in arid and semi
      arid zones is the reduced feed intake and consequent low growth rate during
      summer. Under these stressful environmental conditions, chromium (Cr)
      supplementation to the diet of growing camel calves may be beneficial. Therefore,
      the objective of this study was to evaluate the effects of feeding a diet
      supplemented with different levels of Cr on growth performance of camel calves
      reared in a hot arid environment. A total of 15 male camel calves (4-5-month-old,
      123 +/- 7 kg body weight) were used in this study. The animals were divided into
      three equal groups (A, B, C), 5 animals each, and housed individually under
      shelter. Camel calves were fed ad libitum on either total mixed ration (TMR)
      without Cr supplementation (group A), TMR supplemented with 0.5 mg Cr/kg DM
      (group B), or TMR supplemented with 1.0 mg Cr/kg DM (group C). Supplementation of
      0.5 mg Cr/kg DM to the diet of camel calves did not alter feed intake, however,
      increased not significantly (P = 0.086) average daily gain (ADG) and N retention.
      Plasma cortisol level was reduced by 10%, and feed utilization efficiency was
      improved by 12% in 0.5 mg Cr/kg DM-supplemented group compared to the control.
      Thus, 0.5 mg Cr/kg DM dietary supplementation to camel calves reared under hot
      summer condition increased weight gain by 17% and reduced feeding cost of
      producing a unit of weight by 11%.

PMID- 25589426
TI  - The CarO rhodopsin of the fungus Fusarium fujikuroi is a light-driven proton pump
      that retards spore germination.
AB  - Rhodopsins are membrane-embedded photoreceptors found in all major taxonomic
      kingdoms using retinal as their chromophore. They play well-known functions in
      different biological systems, but their roles in fungi remain unknown. The
      filamentous fungus Fusarium fujikuroi contains two putative rhodopsins, CarO and
      OpsA. The gene carO is light-regulated, and the predicted polypeptide contains
      all conserved residues required for proton pumping. We aimed to elucidate the
      expression and cellular location of the fungal rhodopsin CarO, its presumed
      proton-pumping activity and the possible effect of such function on F. fujikuroi
      growth. In electrophysiology experiments we confirmed that CarO is a green-light
      driven proton pump. Visualization of fluorescent CarO-YFP expressed in F.
      fujikuroi under control of its native promoter revealed higher accumulation in
      spores (conidia) produced by light-exposed mycelia. Germination analyses of
      conidia from carO(-) mutant and carO(+) control strains showed a faster
      development of light-exposed carO(-) germlings. In conclusion, CarO is an active
      proton pump, abundant in light-formed conidia, whose activity slows down early
      hyphal development under light. Interestingly, CarO-related rhodopsins are
      typically found in plant-associated fungi, where green light dominates the
      phyllosphere. Our data provide the first reliable clue on a possible biological
      role of a fungal rhodopsin. 

PMID- 25589433
TI  - Pre-filled syringes: a review of the history, manufacturing and challenges.
AB  - Pre-filled syringes are convenient devices for the delivery of parenteral
      medications. They are small which makes them easy to carry and are dependable for
      delivering a precise dose of medication. These and many other reasons are leading
      to their growth in the pharmaceutical market. There are a number of review
      articles that describe the advantages and disadvantages of pre-filled syringes.
      However, there are few journal articles that present information on their
      manufacturing and challenges. The intent of this review article is to provide
      information on the history of the pre-filled syringe, methods of their
      manufacture, methods of filling syringes as a drug product and to examine the
      types of syringes available. This type of knowledge can familiarize the
      formulation scientist with the choices available and their possible challenges.

PMID- 25589434
TI  - Potential for use of industrial waste materials as filter media for removal of
      Al, Mo, As, V and Ga from alkaline drainage in constructed wetlands--adsorption
      studies.
AB  - The potential to remove Al, Mo, V, As and Ga from alkaline (pH 8.0-8.6) drainage
      originating from seawater neutralized bauxite processing residue storage areas
      using constructed wetland technology was studied in a laboratory study. Bauxite
      processing residue sand, bauxite, alum water treatment sludge and blast furnace
      slag were investigated as potential active filter materials. Al was shown to
      precipitate as Al(OH)3 in the pH range 7.0-8.0 in aqueous solution and 6.0-8.5 in
      the presence of silica sand particles that provided a surface for nucleation. For
      V As Mo and Ga, adsorption to the surfaces of the adsorbents decreased greatly at
      elevated pH values (>pH 6-9). Water treatment sludge and bauxite had a greater
      ability to adsorb V, As and Mo at high pH (As and V at pH 7-9 and Mo at pH 5-7)
      than processing sand and slag. Adsorption isotherm data for As and V onto all
      four adsorbent than processing sand and slag. Adsorption isotherm data for As and
      V onto all four adsorbent materials fitted equally well to the Langmuir and
      Freundlich equations but for Ga, and to a lesser extent Mo, the Freundlich
      equation gave higher R(2) values. For all four ions, the maximum adsorption
      capacity (Langmuir value qmax) was greatest for water treatment sludge. Bauxite
      adsorbed more Mo, Ga and V than residue sand or slag. The pseudo-second order
      equation gave a better fit to the experimental kinetic data than the pseudo-first
      order model suggesting that chemisorption rather than diffusion/exchange was the
      rate limiting step to adsorption. It was concluded that water treatment sludge
      and bauxite were the most effective adsorbents and that for effective removal of
      the target ions the pH of the drainage water needs to be decreased to 6.0-7.0. 

PMID- 25589435
TI  - Modeling the anaerobic digestion of cane-molasses vinasse: extension of the
      Anaerobic Digestion Model No. 1 (ADM1) with sulfate reduction for a very high
      strength and sulfate rich wastewater.
AB  - This research presents the modeling of the anaerobic digestion of cane-molasses
      vinasse, hereby extending the Anaerobic Digestion Model No. 1 with sulfate
      reduction for a very high strength and sulfate rich wastewater. Based on a
      sensitivity analysis, four parameters of the original ADM1 and all sulfate
      reduction parameters were calibrated. Although some deviations were observed
      between model predictions and experimental values, it was shown that sulfates,
      total aqueous sulfide, free sulfides, methane, carbon dioxide and sulfide in the
      gas phase, gas flow, propionic and acetic acids, chemical oxygen demand (COD),
      and pH were accurately predicted during model validation. The model showed high
      (+/-10%) to medium (10%-30%) accuracy predictions with a mean absolute relative
      error ranging from 1% to 26%, and was able to predict failure of methanogenesis
      and sulfidogenesis when the sulfate loading rate increased. Therefore, the
      kinetic parameters and the model structure proposed in this work can be
      considered as valid for the sulfate reduction process in the anaerobic digestion
      of cane-molasses vinasse when sulfate and organic loading rates range from 0.36
      to 1.57 kg [Formula: see text]  m(-3) d(-1) and from 7.66 to 12 kg COD m(-3) d(
      1), respectively. 

PMID- 25589437
TI  - The multidisciplinary depression guideline for children and adolescents: an
      implementation study.
AB  - It is important that depressed patients receive adequate and safe care as
      described in clinical guidelines. The aim of this study was to evaluate the
      implementation of the Dutch depression guideline for children and adolescents,
      and to identify factors that were associated with the uptake of the guideline
      recommendations. The study took place in specialised child and adolescent mental
      healthcare. An implementation project was initiated to enhance the implementation
      of the guideline. An evaluation study was performed alongside the implementation
      project, using structured registration forms and interviews with healthcare
      professionals. Six multidisciplinary teams participated in the implementation
      study. The records of 655 patients were analysed. After 1 year, 72% of all
      eligible patients had been screened for depression and 38% were diagnosed with
      the use of a diagnostic instrument. The severity of the depression was assessed
      in 77% of the patients during the diagnostic process, and 41% of the patients
      received the recommended intervention based on the depression severity. Of the
      patients that received antidepressants, 25% received weekly checks for suicidal
      thoughts in the first 6 weeks. Monitoring of the patients' response was recorded
      in 32% of the patients. A wide range of factors were perceived to influence the
      uptake of guideline recommendations, e.g. the availability of capable
      professionals, available time, electronic tools and reminders, and the
      professionals' skills and attitudes. With the involvement of the teams,
      recommendations were provided for nationwide implementation of the guideline. In
      conclusion, a systematic implementation programme using stepped care principles
      for the allocation of depression interventions seems successful, but there
      remains room for further improvement.

PMID- 25589439
TI  - Using interactive theater to create socioculturally relevant community-based
      intimate partner violence prevention.
AB  - This article describes the use of interactive theater, audience response
      assessment, and peer educators to create community-generated approaches for
      bystander interventions (i.e., actions taken by people who become aware of
      controlling, abusive and violent behavior of others) to prevent intimate partner
      violence (IPV) and to foster change in community norms. We include a case example
      of an ongoing university-community partnership, which mobilizes community members
      to develop and implement socioculturally relevant IPV prevention programs in
      multiple Asian communities. We used interactive theater at a community event--a
      walk to raise awareness about IPV in South Asian communities--and examined how
      the enacted bystander interventions reflect specific community contexts. We
      detail the challenges and limitations we have encountered in our attempts to
      implement this approach in collaboration with our community partners.

PMID- 25589436
TI  - Gender effects on brain changes in early-onset psychosis.
AB  - Progressive loss of cortical gray matter (GM) and increase of cerebrospinal fluid
      (CSF) have been reported in early-onset psychosis (EOP). EOP typically begins
      during adolescence, a time when developmental brain trajectories differ by
      gender. This study aimed to determine gender differences in progression of brain
      changes in this population. A sample of 61 (21 females) adolescents with a first
      psychotic episode and a matched sample of 70 (23 females) controls underwent both
      baseline and 2-year follow-up anatomical brain imaging assessments. Regional GM
      and CSF volumes were obtained using automated methods based on the Talairach's
      proportional grid system. At baseline, only male patients showed a clear pattern
      of alterations in the frontal lobe relative to controls (smaller GM and larger
      CSF volumes). However, parallel longitudinal changes for male and female patients
      relative to controls were observed, resulting in a common pattern of brain
      changes across both genders: rate of left frontal lobe GM volume loss was larger
      in male (-3.8%) and female patients (-4.2%) than in controls (-0.7% males; -0.4%
      females). The reverse was found for the CSF volume in the left frontal lobe.
      While the GM and CSF volumes of females with EOP appear to be within the normal
      range at initial illness onset, our results point to a similar trajectory of
      increased/accelerated brain changes in both male and female patients with EOP.
      The pattern of progression of brain changes in psychosis appears to be
      independent of gender or structural alterations on appearance of psychotic
      symptoms.

PMID- 25589438
TI  - Online sexual behaviours among Swedish youth: associations to background factors,
      behaviours and abuse.
AB  - Sexual activity online may result in positive experiences for young people, or
      lead them to engage in risky behaviours possibly resulting in sexual assault or
      abuse. The aim of our study was to investigate associations between online sexual
      behaviours among Swedish youth and background factors as well as aspects of well
      being. The behaviours investigated were: having sex online with a contact met
      online, having sex with an online contact offline, posting sexual pictures
      online, and selling sex online. We used data from a representative sample of
      3,432 Swedish youth who were asked about their lifetime experiences as well as
      their experiences within the previous year. We hypothesized that more advanced
      online sexual behaviours were associated with more problematic background
      factors, worse psychosocial well-being and riskier behaviours in general.
      Bivariate relationships were evaluated followed by a multiple logistic regression
      model. Our data suggested that most Swedish youth do not perform any of the
      assessed online sexual behaviours. Young people who reported online sexual
      behaviour showed a more problematic background, rated their health as poorer, had
      a more sexualized life and had experienced more sexual or physical abuse.
      Professionals who work with young people need to help them better evaluate
      potential risks online and offer support when needed. Youths who sell sex online
      are especially at risk and need extra attention, as they might be in greater need
      of protection and therapeutic support. 

PMID- 25589441
TI  - Self-organized assemblies of colloidal particles obtained from an aligned
      chromonic liquid crystal dispersion.
AB  - The behavior of mono-disperse colloidal particles in a chromonic liquid crystal
      was investigated. Poly(methyl methacrylate) spherical particles with three
      different functionalizations, with and without surface charges, were utilized in
      the nematic and columnar phases of disodium cromoglycate solutions. The nematic
      phase was completely aligned parallel to the glass substrates by a simple rubbing
      technique, and the columnar phase showed regions of similar alignment. The
      behavior of the colloidal particles in the chromonic liquid crystal depended
      critically on the functionality, with bromine functionalized particles not
      dispersing at all, and cationic trimethylammonium and epoxy functionalized
      particles dispersing well in the isotropic phase of the liquid crystal. At the
      transition to the nematic and especially the columnar phase, the colloidal
      particles were expelled into the remaining isotropic phase. Since the columnar
      phase grew in parallel ribbons, the colloidal particles ended up in chain-like
      assemblies. Such behavior opens the possibility of producing patterned assemblies
      of colloidal particles by taking advantage of the self-organized structure of
      chromonic liquid crystals. 

PMID- 25589443
TI  - Editor's spotlight/take 5: Natural polyphenols enhance stability of crosslinked
      UHMWPE for joint implants.

PMID- 25589442
TI  - Interactive effects of neurocognitive impairment and substance use on
      antiretroviral non-adherence in HIV disease.
AB  - While numerous studies have established the adverse independent effects of
      clinical conditions including neurocognitive dysfunction, psychiatric illness,
      and substance abuse/dependence on medication adherence among HIV-infected adults,
      fewer have studied their interactive effects. The current study examined this
      issue among 204 HIV-infected participants based upon current neurocognitive
      functioning and DSM-IV-diagnosed psychiatric illness and current substance abuse
      or dependence. Results confirmed that participants with any of these risk factors
      demonstrated poorer adherence than individuals with no risk factors. A
      neurocognitive status * substance abuse/dependence interaction was also
      identified such that participants with impaired neurocognition and a co-occurring
      substance abuse/dependence diagnosis demonstrated the poorest adherence. Results
      confirm the deleterious impact of these risk factors in isolation and also
      identify a specific interactive effect for individuals with comorbid
      neurocognitive impairment and a substance abuse/dependence disorder. Findings
      highlight the need for interventions that simultaneously address these problems. 

PMID- 25589440
TI  - The Release 6 reference sequence of the Drosophila melanogaster genome.
AB  - Drosophila melanogaster plays an important role in molecular, genetic, and
      genomic studies of heredity, development, metabolism, behavior, and human
      disease. The initial reference genome sequence reported more than a decade ago
      had a profound impact on progress in Drosophila research, and improving the
      accuracy and completeness of this sequence continues to be important to further
      progress. We previously described improvement of the 117-Mb sequence in the
      euchromatic portion of the genome and 21 Mb in the heterochromatic portion, using
      a whole-genome shotgun assembly, BAC physical mapping, and clone-based finishing.
      Here, we report an improved reference sequence of the single-copy and middle
      repetitive regions of the genome, produced using cytogenetic mapping to mitotic
      and polytene chromosomes, clone-based finishing and BAC fingerprint verification,
      ordering of scaffolds by alignment to cDNA sequences, incorporation of other map
      and sequence data, and validation by whole-genome optical restriction mapping.
      These data substantially improve the accuracy and completeness of the reference
      sequence and the order and orientation of sequence scaffolds into chromosome arm
      assemblies. Representation of the Y chromosome and other heterochromatic regions
      is particularly improved. The new 143.9-Mb reference sequence, designated Release
      6, effectively exhausts clone-based technologies for mapping and sequencing.
      Highly repeat-rich regions, including large satellite blocks and functional
      elements such as the ribosomal RNA genes and the centromeres, are largely
      inaccessible to current sequencing and assembly methods and remain poorly
      represented. Further significant improvements will require sequencing
      technologies that do not depend on molecular cloning and that produce very long
      reads. 

PMID- 25589445
TI  - On patient safety: surgical complications do not always produce poor outcomes
      (just bad feelings).

PMID- 25589444
TI  - The 50 Most-cited Articles in Orthopaedic Surgery From Mainland China.
AB  - BACKGROUND: Citation analysis has been widely used to evaluate the impact of
      articles in medical and surgical specialties. Although China is the most populous
      country in the world, and although more than 50,000 orthopaedic surgeons practice
      there, to our knowledge no formal citation analysis of Chinese orthopaedic
      articles has been performed. QUESTIONS/PURPOSES: We identified the 50 most-cited
      orthopaedic articles from mainland China and evaluated these articles in terms of
      their language of publication, source journals, and topics. METHODS: Science
      Citation Index Expanded was searched in July 31, 2014 for citations of articles
      published in 70 selected journals since the inception of the database. The 50
      most-cited orthopaedic articles originating in mainland China were identified.
      Basic information, including title, authors, year of publication, article type,
      journal in which the work was published, city, institution, number of citations,
      decade published, and topic or subspecialty of the research were recorded.
      RESULTS: The number of citations for the top 50 papers ranged from 181 to 31
      (mean, 52). These articles were published between 1981 and 2010. The decade of
      2000 to 2009 was the most prolific, with 36 of the top 50 articles published
      during this time. All articles were written in English and they were published in
      a total of 16 journals. The journal Spine published the largest number of
      articles (12), followed by Clinical Orthopaedics and Related Research ((r))
      (seven). The journal Lancet had the highest impact factor (39.207 for 2013) among
      any of the journals that published articles we identified. The top 50 articles
      originated mainly from Beijing (16) and Shanghai (12), with basic research being
      the focus of the majority (27 of 50; 54%); the remaining were clinical studies.
      Bone was the most-investigated topic in basic research; the spine was the most
      common topic among the identified clinical studies. CONCLUSIONS: The 50 most
      cited articles that we identified should be considered influential, although a
      large gap remains between mainland China and the global orthopaedic community in
      terms of citations per article. Nevertheless, insofar as the most-recent decade
      of our survey generated the most articles in this top-50 list, we would
      characterize mainland China's effect on musculoskeletal research as increasing,
      and as funding increases to programs in mainland China, we anticipate this trend
      will continue in the future.

PMID- 25589446
TI  - LcBiP, a endoplasmic reticulum chaperone binding protein gene from Lycium
      chinense, confers cadmium tolerance in transgenic tobacco.
AB  - Cadmium (Cd) accumulation is very toxic to plants. The presence of Cd may lead to
      excessive production of reactive oxygen species (ROS), and then cause inhibition
      of plant growth. The endoplasmic reticulum chaperone binding protein (BiP) is an
      important functional protein, which has been shown to function as a sensor of
      alterations in the ER environment. BiP overexpression in plants was shown to
      increase drought tolerance through inhibition of ROS accumulation. Due to the
      above relationships, it is likely that there may be a link between Cd stress
      tolerance, ROS accumulation and the BiP transcript expression in plants. In this
      study, a BiP gene, LcBiP, from L. chinense was isolated and characterized.
      Overexpression of LcBiP in tobacco conferred Cd tolerance. Under Cd stress
      conditions, the transgenic tobacco lines exhibited better chlorophyll retention,
      less accumulation of ROS, longer root length, more glutathione (GSH) content, and
      less antioxidant enzyme activity than the wild type. These data demonstrated that
      LcBiP act as a positive regulator in Cd stress tolerance. It is hypothesized that
      the improved Cd tolerance of the transgenic tobacco plants may be due to the
      enhanced ROS scavenging capacity. The enhancement of GSH content might contribute
      to this ROS scavenging capacity in the transgenic plants. However, the underlying
      mechanism for BiP-mediated increase in Cd stress tolerance need to be further
      clarified.

PMID- 25589448
TI  - Convenient and highly efficient routes to 2 H-chromene and 4-chromanone
      derivatives: iodine-promoted and p-toluenesulfonic acid catalyzed cascade
      cyclizations of propynols.
AB  - A convenient strategy is presented for the easy preparation of a series of 2 H
      chromenes under mild conditions through iodocyclization of readily accessible
      propynols. In addition, various 4-chromanones can be synthesized through a p
      toluenesulfonic acid catalyzed cascade cyclization with high efficiency (yields
      up to 99 %). Our developed reaction systems are proven to have good functional
      group applicability and can be scaled up to gram quantities in satisfactory
      yields. These systems also provide a new synthetic strategy for two types of
      important flavonoid skeleton without using costly and toxic metal catalysts.
      Additionally, the resulting halides could be further exploited in subsequent
      palladium-catalyzed coupling reactions, so these compounds could act as potential
      intermediates for the construction of some valuable drug molecules. 

PMID- 25589449
TI  - Meniscal allograft sterilisation: effect on biomechanical and histological
      properties.
AB  - Sterilisation of allografts are a crucial step in ensuring safety and viability.
      Current sterilisation standards such as 25 kGy gamma irradiation (gamma) can have
      adverse effects on the ultrastructure and biomechanical properties of allograft
      tissue. Supercritical CO2 (SCCO2) technology, represents an improved
      sterilisation process that potentially preserves tissue properties. This study
      aimed to test the effect of SCCO2 sterilisation on the biomechanical and
      histological properties of the meniscus and compare this to the current standard
      of gamma. Thirty-two 18-month old ovine menisci were randomly assigned into three
      groups for sterilisation (SCCO2, gamma and control). After treatment,
      biomechanical indentation testing (stiffness and stress relaxation) or
      histological analysis [percentage of void, cells and extracellular matrix (ECM)
      per slide] was undertaken. Both SCCO2 and gamma groups displayed an increase in
      stiffness and stress relaxation as compared to control, however, this difference
      was lesser in samples treated with SCCO2. No significant histological
      quantitative differences were detected between SCCO2 and control specimens. Gamma
      treated samples demonstrated a significant increase in void and decrease in ECM.
      Interestingly, both treatment groups demonstrated a decreasing mean void and
      increasing ECM percentage when analysed from outer to inner zones. No significant
      differences were detected in all-endpoints when analysed by section. SCCO2
      sterilisation represents a potential feasible alternative to existing
      sterilization techniques such as gamma.

PMID- 25589447
TI  - Attention modulates cortical processing of pitch feedback errors in voice
      control.
AB  - Considerable evidence has shown that unexpected alterations in auditory feedback
      elicit fast compensatory adjustments in vocal production. Although generally
      thought to be involuntary in nature, whether these adjustments can be influenced
      by attention remains unknown. The present event-related potential (ERP) study
      aimed to examine whether neurobehavioral processing of auditory-vocal integration
      can be affected by attention. While sustaining a vowel phonation and hearing
      pitch-shifted feedback, participants were required to either ignore the pitch
      perturbations, or attend to them with low (counting the number of perturbations)
      or high attentional load (counting the type of perturbations). Behavioral results
      revealed no systematic change of vocal response to pitch perturbations
      irrespective of whether they were attended or not. At the level of cortex, there
      was an enhancement of P2 response to attended pitch perturbations in the low-load
      condition as compared to when they were ignored. In the high-load condition,
      however, P2 response did not differ from that in the ignored condition. These
      findings provide the first neurophysiological evidence that auditory-motor
      integration in voice control can be modulated as a function of attention at the
      level of cortex. Furthermore, this modulatory effect does not lead to a general
      enhancement but is subject to attentional load. 

PMID- 25589450
TI  - Potential of 5-azacytidine induction decidual stromal cells from maternal human
      term placenta towards cardiomyocyte-like cells in serum-free medium.
AB  - Decidual stromal cells (DSCs) from maternal term placenta represent a potential
      source of cells for the treatment of cardiovascular and graft-versus-host
      diseases. However, it is not clear whether DSCs could be induced towards
      cardiomyocyte-like differentiation. We chose the placentas which should bred male
      new-baby. We isolated DSCs from placenta by tissue adherence. The morphology,
      immunophenotype, and multi-lineage potential were analyzed. Karyotype analysis (G
      band) was performed to determine the source and karyotype stability of DSCs. DSCs
      were induced by 5-azacytidine. Expression of Myf5, alpha-cardiac actin, Cardiac
      troponin T (cTnT) and GAPDH was assessed by PCR, and cTnT expression was also
      analyzed by immunofluorescence. Karyotype analyses indicated that cells were
      derived from the maternal matrix. After induction with 5-azacytidine, DSCs
      expressed the cardiac-specific markers Myf5, myogenin and cTnT, indicating
      differentiation towards cardiomyocyte-like cells. 

PMID- 25589451
TI  - The relationship between maternal postpartum psychological state and breast milk
      secretory immunoglobulin A level.
AB  - BACKGROUND: Maternal psychological state may influence the passive transfer of
      immune factors (e.g., immunoglobulin) via the mother's breast milk. OBJECTIVE:
      The aim of this study was to determine whether a correlation exists between
      mothers' postpartum psychological state and their breast milk secretory
      immunoglobulin A (SIgA) levels. STUDY DESIGN: Eighty-one mothers who delivered at
      an urban general hospital were included in our analysis. Two weeks after
      delivery, we measured their breast milk SIgA levels and simultaneously documented
      their psychological state using the Profile of Mood States (POMS), General Health
      Questionnaire (GHQ), and State-Trait Anxiety Inventory (STAI) scales. RESULTS:
      Breast milk SIgA levels were negatively correlated with negative POMS states
      (tension-anxiety, depression-dejection, anger-hostility, fatigue, and confusion).
      A negative correlation was also observed between SIgA levels and GHQ mental
      health (r = -.625, P = .000), and a similar negative correlation was observed
      with STAI trait and state anxieties. However, no correlation existed between
      breast milk SIgA levels and the positive POMS state (vigor). CONCLUSIONS: These
      results indicate that the maternal psychological state may affect the immune
      properties of breast milk.

PMID- 25589452
TI  - Parental involvement in youth anxiety treatment: conceptual bases, controversies,
      and recommendations for intervention.
AB  - Parents are often perceived as a contributing or maintaining source of youth
      anxiety disorders, making them natural targets for either intervention or
      involvement in treatment protocols. Efforts to increase the efficacy and
      durability of standard treatments by incorporating parents have been successful,
      yet they often do not outperform child-focused treatment. Breinholst et al.
      (2012) review and discuss several overlooked parental research variables
      (anxiety, overcontrol, beliefs and assumptions, global family dysfunction) found
      to promote and maintain child anxiety. However, it remains unclear how these
      proposed variables interfere with active therapeutic ingredients (e.g., exposure)
      or how the identified problems might be addressed. We propose that insufficient
      attention to exposure-based treatment and family behavioral responses explain the
      comparatively low added value for parental involvement in child anxiety treatment
      and outline directions for research to address them. With meaningful attention
      being given to exposure and its accompanying variables in the treatment of
      childhood anxiety, we believe that treatment outcomes and intervention
      acceptability can be improved. 

PMID- 25589453
TI  - Effectiveness of cognitive-behavioral group therapy for patients with
      hypochondriasis (health anxiety).
AB  - Cognitive behavioral therapy (CBT) has been shown to be highly effective in the
      treatment of health anxiety. However, little is known about the effectiveness of
      group CBT in the treatment of health anxiety. The current study is the largest
      study that has investigated the effectiveness of combined individual and group
      CBT for patients with the diagnosis of hypochondriasis (N=80). Therapy outcomes
      were evaluated by several questionnaires. Patients showed a large improvement on
      these primary outcome measures both post-treatment (Cohen's d=0.82-1.08) and at a
      12-month follow-up (Cohen's d=1.09-1.41). Measures of general psychopathology and
      somatic symptoms showed significant improvements, with small to medium effect
      sizes. Patients with more elevated hypochondriacal characteristics at therapy
      intake showed a larger therapy improvement, accounting for 7-8% of the variance
      in therapy outcome. CBT group therapy has therefore been shown to be an
      appropriate and cost-effective treatment for health anxiety. 

PMID- 25589455
TI  - A case of pancreaticobiliary fistula associated with an   intraductal papillary
      mucinous neoplasm of the pancreas.

PMID- 25589454
TI  - Feasibility of pre-operative chemoradiotherapy with gemcitabine to treat
      pancreatic cancer in patients with impaired renal function.
AB  - OBJECTIVE: Although pre-operative chemoradiotherapy appears to be a promising
      treatment for patients with pancreatic ductal adenocarcinoma, there have been no
      reports of the feasibility of pre-operative chemoradiotherapy in pancreatic
      ductal adenocarcinoma patients with renal impairment. The aim of this study was
      to evaluate retrospectively the feasibility of pre-operative chemoradiotherapy in
      pancreatic ductal adenocarcinoma patients with renal impairment. METHODS: Twelve
      patients with resectable pancreatic ductal adenocarcinoma and a creatinine
      clearance of <60 ml/min were enrolled in this study. Gemcitabine-based pre
      operative chemoradiotherapy was performed, followed by surgery. The feasibility
      of the treatment was evaluated in terms of clinical outcome and adverse events in
      the patients. RESULTS: All 12 patients completed gemcitabine-based pre-operative
      chemoradiotherapy without worsening of renal function. Restaging after the
      therapy revealed radiologically unresectable disease in two patients. Among the
      remaining 10 patients who underwent laparotomy, curative resection was performed
      in eight patients. After curative resection, five patients out of the eight
      completed post-operative adjuvant therapy. The 1- and 3-year survival rates after
      the start of chemoradiotherapy in the 12 patients were 80.8 and 36.9%,
      respectively. CONCLUSIONS: Our findings suggest that gemcitabine-based pre
      operative chemoradiotherapy may be a safe and effective treatment for pancreatic
      ductal adenocarcinoma in patients with renal impairment.

PMID- 25589456
TI  - Methodological issues in observational studies and non-randomized controlled
      trials in oncology in the era of big data.
AB  - Non-randomized controlled trials, cohort studies and database studies are
      appealing study designs when there are urgent needs for safety data, outcomes of
      interest are rare, generalizability is a matter of concern, or randomization is
      not feasible. This paper reviews four typical case studies from methodological
      viewpoints and clarifies how to minimize bias in observational studies in
      oncology. In summary, researchers planning observational studies should be
      cautious of selection of appropriate databases, validity of algorithms for
      identifying outcomes, comparison with incident users or self-control, rigorous
      collection of information on potential confounders and reporting details of
      subject selection. Further, a careful study protocol and statistical analysis
      plan are also necessary. 

PMID- 25589457
TI  - Inhalation devices and patient interface: human factors.
AB  - The development of any inhalation product that does not consider the patient
      needs will fail. The needs of the patients must be identified and aligned with
      engineering options and physical laws to achieve a robust and intuitive-to-use
      inhaler. A close interaction between development disciplines and real-use
      evaluations in clinical studies or in human factor studies is suggested. The same
      holds true when a marketed product needs to be changed. Caution is warranted if
      an inhaler change leads to a change in the way the patient handles the device.
      Finally, the article points out potential problems if many inhaler designs are
      available. Do they confuse the patients? Can patients recall the correct handling
      of each inhaler they use? How large is the risk that different inhaler designs
      pose to the public health? The presentations were given at the Orlando Inhalation
      Conference: Approaches in International Regulation co-organised by the University
      of Florida and the International Pharmaceutical Aerosol Consortium on Regulation
      & Science (IPAC-RS) in March 2014. 

PMID- 25589458
TI  - Is there an ideal outcome scoring system for facial reanimation surgery? A review
      of current methods and suggestions for future publications.
AB  - Facial reanimation is the surgical process of attempting to restore dynamic,
      spontaneous symmetry to the paralysed face. We undertook to review the most
      frequently used scoring systems and discuss a universal set of assessments which
      every facial palsy surgeon can use to standardize the outcome of surgical
      intervention and allow a comparison to be drawn when comparing different
      operative techniques. A literature review was performed using PubMed and Cochrane
      databases to identify scoring systems for facial palsy, facial nerve regeneration
      and facial reanimation. The scoring systems were broken down into the following
      broad categories: observational, mathematical and computer-graphical
      measurements. More than 20 scoring systems were identified and included in the
      study. The scoring systems were analysed and assessed for reproducibility and
      inter-observer reliability. The current trend in the literature is to use the
      House-Brackmann Score due to its historical longevity, brevity and ease of
      understanding. However, this was never designed to assess outcomes of facial
      reanimation and there are clear limitations. Other more appropriate methods such
      as 3-D facial analysis are prohibitively expensive to widely implement. The quest
      continues to develop an ideal system. From this review it is clear that a quick,
      simple to use system should be used which incorporates the patient's own views.
      Therefore a combination of pre- and post-operative photographs of the patient
      should be assessed by an independent panel as well as the patient. We propose a
      universal set of photographs that can be used to standardize the outcome of
      surgical intervention when publishing results in the literature. This will allow
      a comparison to be drawn when comparing different operative techniques and help
      surgeons work collectively towards the same goal while improving patient
      outcomes. 

PMID- 25589459
TI  - A systematic review of post-surgical pyoderma gangrenosum: identification of risk
      factors and proposed management strategy.
AB  - BACKGROUND: Post-surgical pyoderma gangrenosum (PSPG) presents as a rapidly
      expanding cutaneous ulcer at a site of surgery with potentially devastating
      consequences. We systematically reviewed the English and foreign language
      literature to identify risk factors for PSPG and propose a management strategy.
      METHODS: A systematic review was completed in PubMed, Medline, Embase, and
      Cochrane Database for all published reports of PSPG from January 1946 to June
      2013. We manually examined bibliographies for relevant references and used Google
      Translate for articles in foreign languages, including Italian, Japanese, German,
      Dutch, Turkish, Spanish, Chinese, Dutch, Russian, Portuguese, and Czech. RESULTS:
      We identified 220 cases of PSPG (mean age 52.8 years, range 5-85 years). Thirty
      seven patients (16.8%) had a history of pyoderma gangrenosum, nineteen (8.6%) had
      a hematologic disorder such as leukemia or lymphoma, thirteen (5.9%) had
      inflammatory bowel disease, and eight (3.6%) had rheumatoid arthritis. PSPG
      occurred most commonly after breast (25%), cardiothoracic (14%), abdominal (14%),
      and obstetric (13%) surgeries. The most common breast procedures were bilateral
      reduction mammoplasty (45%), breast reconstruction (25%), and lumpectomy or
      mastectomy (11%). Signs of wound complication occurred on average 7.0 days after
      surgery. Nineteen patients (8.6%) at risk for PSPG received perioperative
      corticosteroids during skin grafting or later surgeries with a favorable outcome.
      CONCLUSIONS: Patients with a history of pyoderma gangrenosum, rheumatoid
      arthritis, inflammatory bowel disease, or hematologic malignancy who are
      undergoing breast, cardiothoracic, or abdominal surgeries should be carefully
      observed for post-operative ulceration at incision sites. Debridement should not
      be performed before dermatologic consultation to assess for PSPG. Patients at
      risk of PSPG undergoing breast surgery may benefit from perioperative prednisone
      to prevent PSPG which can lead to destructive wound enlargement and significant
      scarring.

PMID- 25589460
TI  - A simple technique for orientation of neck dissection specimens.

PMID- 25589461
TI  - RBPJ inhibition impairs the growth of lung cancer.
AB  - The exact effects of the modulation of Notch signaling pathway on cell growth
      have been shown to depend on tumor cell type. Recombination signal-binding
      protein Jkappa (RBPJ) is a key transcription factor downstream of receptor
      activation in Notch signaling pathway. Here, we evaluated the effects of RBPJ
      inhibition on the growth of lung cancer cells. We found that a short hairpin
      interfering RNA (shRNA) for RBPJ efficiently inhibited RBPJ expression in lung
      cancer cells, resulting in a significant decrease in the cell growth. Further
      analyses showed that RBPJ inhibition altered the levels of its downstream
      targets, including p21, p27, CDK2, Hes1, Bcl-2, and SKP2, to prevent the cells
      from growing. Our data thus suggest that shRNA intervention of RBPJ expression
      could be a promising therapeutic approach for treating human lung cancer. 

PMID- 25589462
TI  - Indole-3-carbinol suppresses NF-kappaB activity and stimulates the p53 pathway in
      pre-B acute lymphoblastic leukemia cells.
AB  - B cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common type
      of cancer in children. Dramatic improvements in primary therapy for childhood ALL
      have led to an overall cure rate of 80 %, providing opportunities for innovative
      combined-modality strategies that would increase cure rates while reducing the
      toxic side effects of current intensive regimens. In this study, we report that
      indole-3-carbinol (I3C), a natural phytochemical found in cruciferous vegetables,
      had anti-leukemic properties in BCP-ALL NALM-6 cells. I3C induced cell growth
      inhibition by G1 cell cycle arrest and triggered apoptosis in a dose- and time
      dependent manner. p53, p21, and Bax proteins showed increased expression after
      I3C treatment. Real-time PCR analysis of pro-apoptotic p53 target genes revealed
      up-regulation of PUMA, NOXA, and Apaf-1. I3C also suppressed constitutive nuclear
      factor-kappaB (NF-kappaB) activation and inhibited the protein expression of NF
      kappa B-regulated antiapoptotic (IAP1, Bcl-xL, Bcl-2, XIAP) and proliferative (c
      Myc) gene products. Coadministration of I3C with the topoisomerase II inhibitor,
      doxorubicin, potentiates cytotoxic effects compared with either agent alone.
      Apoptosis induction by the drug combination was associated with enhanced caspase
      9 activation and PARP cleavage. Furthermore, I3C abolished doxorubicin-induced NF
      kappaB activity as evidenced by decreased nuclear accumulation of p65, inhibition
      of IkappaBalpha phosphorylation and its degradation, and decreased NF-kappaB DNA
      binding activity. Western blot analysis revealed that doxorubicin-induced Bcl-2
      protein expression was inhibited by I3C. Overall, our results indicated that
      using nontoxic agents, such as I3C, in combination with anthracyclines might
      provide a new insight into the development of novel combination therapies in
      childhood BCP-ALL.

PMID- 25589465
TI  - Ordered mesoporous silica films with pores oriented perpendicular to a titanium
      nitride substrate.
AB  - The production of thin mesoporous silica films with small (~2-3 nm) pores
      oriented perpendicular to a titanium nitride growth surface is demonstrated using
      two methods. These are the growth from a Stober silica solution with surfactant
      ordering at the surface of the electrode, and electrochemically assisted growth
      from an acidic sol achieved by polarisation of the electrode surface. The
      thickness, pore order and pore size that can be achieved with these two methods
      is contrasted. A number of methods to vary the pore size by using different
      surfactants and swelling agents are explored. The advantage of applying these
      growth methods on titanium nitride surfaces is that it provides access to a wider
      electrochemical window for nanowire growth and sensor applications with non
      aqueous electrolytes whilst retaining good film growth and adhesion properties. 

PMID- 25589463
TI  - SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through
      targeting lipid metabolism.
AB  - Sterol regulatory element-binding protein 1 (SREBP1) is a known transcription
      factor of lipogenic genes, which plays important roles in regulating de novo
      lipogenesis. Accumulating evidences indicate SREBP1 is involved in tumorigenesis,
      yet its role in pancreatic cancer remains unclear. Here, we explored the
      expression characteristic and function of SREBP1 in pancreatic cancer. Analysis
      of 60 patients with pancreatic ducat cancer showed that SREBP1 level was
      significantly higher in pancreatic cancer than that in adjacent normal tissues.
      High expression of SREBP1 predicted poor prognosis in patients with pancreatic
      cancer. Multivariate analysis revealed that SREBP1 was an independent factor
      affecting overall survival. SREBP1 silencing resulted in proliferation inhibition
      and induction of apoptosis in pancreatic cancer cells. Mechanistically, lipogenic
      genes (acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), and stearoyl-CoA
      desaturase-1 (SCD1)) and de novo lipogenesis were promoted by SREBP1. Inhibition
      of lipogenic genes through specific inhibitors ablated SREBP1-mediated growth
      regulation. Furthermore, depletion of SREBP1 could suppress lipid metabolism and
      tumor growth in vivo. Our results indicate that SREBP1 had important role in
      tumor progression and appears to be a novel prognostic marker for pancreatic
      cancer.

PMID- 25589464
TI  - Stable knockdown of LRG1 by RNA interference inhibits growth and promotes
      apoptosis of glioblastoma cells in vitro and in vivo.
AB  - Leucine-rich alpha2 glycoprotein 1 (LRG1) has been shown to be aberrantly
      expressed in multiple human malignancies. However, the biological functions of
      LRG1 in human glioblastoma remain unknown. Here, we report for the first time the
      role of LRG1 in glioblastoma development based on the preliminary in vitro and in
      vivo data. We first confirmed the expression of LRG1 in human glioblastoma cell
      lines. Next, to investigate the role of LRG1 in the tumorigenesis and development
      of glioblastoma, a short hairpin RNA (shRNA) construct targeting LRG1 mRNA was
      transfected into U251 glioblastoma cells to generate a cell line with stably
      silenced LRG1 expression. The results showed that silencing of LRG1 significantly
      inhibited cell proliferation, induced cell cycle arrest at G0/G1 phase, and
      enhanced apoptosis in U251 cells in vitro. Consistently, LRG1 silencing resulted
      in the downregulation of key cell cycle factors including cyclin D1, B, and E and
      apoptotic gene Bcl-2 while elevated the levels of pro-apoptotic Bax and cleaved
      caspase-3, as determined by Western blot analysis. We further demonstrate that
      the silencing of LRG1 expression effectively reduced the tumorigenicity of U251
      cells, delayed tumor formation, and promoted apoptosis in a xenograft tumor model
      in vivo. In conclusion, silencing the expression of LRG1 suppresses the growth of
      glioblastoma U251 cells in vitro and in vivo, suggesting that LRG1 may play a
      critical role in glioblastoma development, and it may have potential clinical
      implications in glioblastoma therapy.

PMID- 25589467
TI  - Hole delocalization over adenine tracts in single stranded DNA oligonucleotides.
AB  - Adiabatic ionization energies of single stranded DNA oligonucleotides containing
      adenine tracts of different sizes have been computed at the DFT level and
      compared with the oxidation potentials determined by differential pulse
      voltammetry. Geometry optimizations have been performed at the full quantum
      mechanical level, including the sugar phosphate backbone and solvent effects. The
      observed progressive lowering of the ionization energy upon increasing the number
      of consecutive adenines is well predicted, the computed ionization potential
      shifts being in very good agreement with the experimental outcomes, both by using
      pure and hybrid functionals. The spin density of the oligonucleotide radical
      cations is distributed almost over the whole adenine tract, forming delocalized
      polarons. 

PMID- 25589466
TI  - Factor VIII organisation on nanodiscs with different lipid composition.
AB  - Nanodiscs (ND) are lipid bilayer membrane patches held by amphiphilic scaffolding
      proteins (MSP) of ~10 nm in diameter. Nanodiscs have been developed as lipid
      nanoplatforms for structural and functional studies of membrane and membrane
      associated proteins. Their size and monodispersity have rendered them unique for
      electron microscopy (EM) and single particle analysis studies of proteins and
      complexes either spanning or associated to the ND membrane. Binding of blood
      coagulation factors and complexes, such as the Factor VIII (FVIII) and the Factor
      VIIIa - Factor IXa (intrinsic tenase) complex to the negatively charged activated
      platelet membrane is required for normal haemostasis. In this study we present
      our work on optimising ND, specifically designed to bind FVIII at close to
      physiological conditions. The binding of FVIII to the negatively charged ND rich
      in phosphatidylserine (PS) was followed by electron microscopy at three different
      PS compositions and two different membrane scaffolding protein (MSP1D1) to lipid
      ratios. Our results show that the ND with highest PS content (80 %) and lowest
      MSP1D1 to lipid ratio (1:47) are the most suitable for structure determination of
      the membrane-bound FVIII by single particle EM. Our preliminary FVIII 3D
      reconstruction as bound to PS containing ND demonstrates the suitability of the
      optimised ND for structural studies by EM. Further assembly of the activated
      FVIII form (FVIIIa) and the whole FVIIIa-FIXa complex on ND, followed by EM and
      single particle reconstruction will help to identify the protein-protein and
      protein-membrane interfaces critical for the intrinsic tenase complex assembly
      and function.

PMID- 25589468
TI  - Tunable photoluminescence across the entire visible spectrum from carbon dots
      excited by white light.
AB  - Although reports have shown shifts in carbon dot emission wavelengths resulting
      from varying the excitation wavelength, this excitation-dependent emission does
      not constitute true tuning, as the shifted peaks have much weaker intensity than
      their dominant emission, and this is often undesired in real world applications.
      We report for the first time the synthesis and photoluminescence properties of
      carbon dots whose peak fluorescence emission wavelengths are tunable across the
      entire visible spectrum by simple adjustment of the reagents and synthesis
      conditions, and these carbon dots are excited by white light. Detailed material
      characterization has revealed that this tunable emission results from changes in
      the carbon dots' chemical composition, dictated by dehydrogenation reactions
      occurring during carbonization. These significantly alter the nucleation and
      growth process, resulting in dots with either more oxygen-containing or nitrogen
      containing groups that ultimately determine their photoluminescence properties,
      which is in stark contrast to previous observations of carbon dot excitation
      dependent fluorescence. This new ability to synthesize broadband excitable carbon
      dots with tunable peak emissions opens up many new possibilities, particularly in
      multimodal sensing, in which multiple analytes and processes could be monitored
      simultaneously by associating a particular carbon dot emission wavelength to a
      specific chemical process without the need for tuning the excitation source. 

PMID- 25589469
TI  - Effect of real-time teledermatology on diagnosis, treatment and clinical
      improvement.
AB  - We assessed the effect of real-time teledermatology consultations on diagnosis
      and disease management, patients' quality of life and time- and cost-savings. All
      consecutive patients with skin diseases attending teledermatology clinics at two
      rural hospitals in Jordan were included in the study. Patients were interviewed
      at their initial visit and again after eight weeks. Various questionnaires and
      forms, including quality of life questionnaires, were used to collect the data.
      Ninety teledermatology consultations were performed for 88 patients between
      September 2013 and January 2014. A diagnosis was established as part of the
      teledermatology consultation in 43% of patients and changed from that of the
      referring provider in 19% of patients. The treatment plan was established for 67%
      of patients and changed for 9% patients. The mean SF-8 score increased
      significantly (P < 0.005). The mean DLQI score decreased significantly (P <
      0.005) indicating that there had been an improvement in the patients' quality of
      life since baseline. Most patients perceived that the visit to the
      teledermatology clinic required less travel time (96%), shorter waiting time
      (83%) and less cost (96%) than a visit to the specialist clinic at the main
      hospital. The patients' mean satisfaction score was 90.5 (SD 8.5), indicating a
      high level of satisfaction. Teledermatology resulted in changes in the patients'
      diagnosis and treatment plan, and was associated with improved health state and
      quality of life. 

PMID- 25589470
TI  - Spatially resolved chemical reaction monitoring using magnetic resonance imaging.
AB  - Over the previous three decades, the use of MRI for studying dynamic physical and
      chemical processes of materials systems has grown significantly. This mini-review
      provides a brief introduction to relevant principles of MRI, including methods of
      spatial localization, factors contributing to image contrast, and chemical shift
      imaging. A few historical examples of (1) H MRI for reaction monitoring will be
      presented, followed by a review of recent research including (1) H MRI studies of
      gelation and biofilms, (1) H, (7) Li, and (11) B MRI studies of electrochemical
      systems, in vivo glucose metabolism monitored with (19) F MRI, and in situ
      temperature monitoring with (27) Al MRI. Copyright (c) 2015 John Wiley & Sons,
      Ltd. 

PMID- 25589471
TI  - Fracture fabrication of a multi-scale channel device that efficiently captures
      and linearizes DNA from dilute solutions.
AB  - This paper describes a simple technique for patterning channels on elastomeric
      substrates, at two distinct scales of depth, through the use of controlled
      fracture. Control of channel depth is achieved by the careful use of different
      layers of PDMS, where the thickness and material properties of each layer, as
      well as the position of the layers relative to one another, dictate the depth of
      the channels formed. The system created in this work consists of a single 'deep'
      channel, whose width can be adjusted between the micron- and the nano-scale by
      the controlled application or removal of a uniaxial strain, and an array of
      'shallow' nano-scale channels oriented perpendicular to the 'deep' channel. The
      utility of this system is demonstrated through the successful capture and
      linearization of DNA from a dilute solution by executing a two-step 'concentrate
      then-linearize' procedure. When the 'deep' channel is in its open state and a
      voltage is applied across the channel network, an overlapping electric double
      layer forms within the 'shallow' channel array. This overlapping electric double
      layer was used to prevent passage of DNA into the 'shallow' channels when the DNA
      molecules migrate into the junctional region by electrophoresis. Release of the
      applied strain then allows the 'deep' channel to return to its closed state,
      reducing the cross-sectional area of this channel from the micro- to the nano
      scale. The resulting hydrodynamic flow and nano-confinement effects then combine
      to efficiently uncoil and trap the DNA in its linearized form. By adopting this
      strategy, we were able to overcome the entropic barriers associated with
      capturing and linearizing DNA derived from a dilute solution. 

PMID- 25589472
TI  - Nanostructured Zr-Pd metallic glass thin film for biochemical applications.
AB  - Zr-Pd metallic glassy thin films with a hierarchical nano-scale structure,
      produced by magnetron sputtering of the Zr and Pd powder mixture, demonstrate a
      unique combination of physical and biochemical properties. Thermal stability of
      the nano-structured glassy samples, their resistance to oxidation in dry air and
      phase transformation behavior are discussed in the present work. These binary
      alloy samples also show exceptionally high corrosion resistance and spontaneous
      passivation in a simulated body fluid. Experiments on the catalytic activity and
      biocompatibility of this nanostructured metallic glass indicate that this is a
      very suitable material for biochemical applications. Compared to the
      multicomponent alloys studied earlier this binary alloy has much simpler chemical
      composition, which makes preparation of the sample with defined stoichiometry
      easier, especially when the elements have different sputtering rates. 

PMID- 25589473
TI  - An alkene-promoted borane-catalyzed highly stereoselective hydrogenation of
      alkynes to give Z- and E-alkenes.
AB  - The stereoselective hydrogenation of alkynes to alkenes is an extremely useful
      transformation in synthetic chemistry. Despite numerous reports for the synthesis
      of Z-alkenes, the hydrogenation of alkynes to give E-alkenes is still not well
      resolved. In particular, selective preparation of both Z- and E-alkenes by the
      same catalytic hydrogenation system using molecular H2 has rarely been reported.
      In this paper, a novel strategy of using simple alkenes as promoters for the
      HB(C6 F5 )2 -catalyzed metal-free hydrogenation of alkynes was adopted.
      Significantly, both Z- and E-alkenes can be furnished by hydrogenation with
      molecular H2 in high yields with excellent stereoselectivities. Further
      experimental and theoretical mechanistic studies suggest that interactions
      between H and F atoms of the alkene promoter, borane intermediate, and H2 play an
      essential role in promoting the hydrogenolysis reaction. 

PMID- 25589474
TI  - qPMS9: an efficient algorithm for quorum Planted Motif Search.
AB  - Discovering patterns in biological sequences is a crucial problem. For example,
      the identification of patterns in DNA sequences has resulted in the determination
      of open reading frames, identification of gene promoter elements, intron/exon
      splicing sites, and SH RNAs, location of RNA degradation signals, identification
      of alternative splicing sites, etc. In protein sequences, patterns have led to
      domain identification, location of protease cleavage sites, identification of
      signal peptides, protein interactions, determination of protein degradation
      elements, identification of protein trafficking elements, discovery of short
      functional motifs, etc. In this paper we focus on the identification of an
      important class of patterns, namely, motifs. We study the (l, d) motif search
      problem or Planted Motif Search (PMS). PMS receives as input n strings and two
      integers l and d. It returns all sequences M of length l that occur in each input
      string, where each occurrence differs from M in at most d positions. Another
      formulation is quorum PMS (qPMS), where the motif appears in at least q% of the
      strings. We introduce qPMS9, a parallel exact qPMS algorithm that offers
      significant runtime improvements on DNA and protein datasets. qPMS9 solves the
      challenging DNA (l, d)-instances (28, 12) and (30, 13). The source code is
      available at https://code.google.com/p/qpms9/. 

PMID- 25589475
TI  - The potential drug-drug interactions of ginkgolide B mediated by renal
      transporters.
AB  - Ginkgolide B (GB) is a selective and strong antagonist of platelet-activating
      factor with great benefits in CNS diseases treatment. The renal excretion
      constitutes the predominant secretory pathway of GB. Here, we investigated the
      potential role of renal drug transporters in GB urinary excretion. The
      intravenous administration of GB was conducted at 10 min post-administration of
      probenecid (potential inhibitor of organic anion transporters/organic anion
      transporting polypeptides) or bromosulfophthalein (traditional inhibitor of multi
      drug resistance proteins) in rats. Pretreated with probenecid, the systemic
      exposure of GB was significantly elevated from 8.319 +/- 1.646 to 14.75 +/- 1.328
      ug . mL(-1) ?h but with reduced total clearance from 1.17 +/- 0.331 to 0.596 +/-
      0.0573 L . h(-1) ?kg(-1) accompanying no changes in plasma elimination half-lives
      compared with control group. With no pronounced effect on metabolic elimination,
      the decreased total clearance was closely pertained to the reduced renal
      excretion, indicating the potential effect of organic anion transporters and/or
      organic anion transporting polypeptides in renal secretory of GB from blood to
      urine. However, the possible effect of bromosulfophthalein was restricted within
      a minor extent, suggesting the mild role of multi-drug resistance protein in GB
      renal excretion.

PMID- 25589476
TI  - Impact of the number of Robertsonian chromosomes on germ cell death in wild male
      house mice.
AB  - Previous studies in the house mouse have shown that the presence of Robertsonian
      (Rb) metacentric chromosomes in heterozygous condition affects the process of
      spermatogenesis. This detrimental effect mainly depends on the number of
      metacentrics involved and the complexity of the resulting meiotic figures. In
      this study, we aimed at elucidating the relationship between the chromosomal
      composition and spermatogenesis impairment in mice present in an area of
      chromosomal polymorphism (the so-called Barcelona system BRbS) in which Rb mice
      are surrounded by all acrocentric animals, no established metacentric races are
      present and the level of structural heterozygosity is relatively low. Using the
      terminal deoxinucleotidyl transferase-mediated dUTP nick end labelling (TUNEL)
      assay, we report higher frequency of apoptotic spermatogenetic cells in mice
      carrying six pairs of metacentrics at the homozygous state than in those carrying
      two or three fusions at the heterozygous state. Specifically, we detected a
      higher frequency of TUNEL-positive (T+) tubules and of T+ cells per tubule cross
      section and also a lower spermatid/spermatocyte ratio. These results indicate
      that the number of metacentrics at the homozygous state is more influential in
      determining apoptotic germ cell death than that of moderate chromosome
      heterozygosity. The percentage of germ cell death lower than 50 % found in our
      samples and the geographic distribution of the set of metacentrics within the
      BRbS indicate that although the spermatogenic alterations detected in this area
      could act as a partial barrier to gene flow, they are not sufficient to prevent
      Rb chromosomes from spreading in nature. 

PMID- 25589477
TI  - Relationship between motor skills, participation in leisure activities and
      quality of life of children with Developmental Coordination Disorder: temporal
      aspects.
AB  - The study examined the relationship between motor skills, participation in
      leisure activities and quality of life (QOL), within a temporal context (school
      year vs. summer vacation and school days vs. weekends). Parents of 22 children
      with Developmental Coordination Disorder (DCD) and of 55 typically developing
      children, aged 6-11, filled out two questionnaires relating to their children's
      participation in leisure activities (vigorous, moderate and sedentary) and QOL.
      The Movement Assessment Battery for Children-2 (MABC-2) was administered to their
      children. Results showed that among the children with DCD, balance scores
      positively correlated with participation in sedentary activities, and in both
      groups both balance and aiming and catching were related to the physical and
      school aspects of QOL. Furthermore, participation in vigorous activities in the
      summer was positively correlated with social and school QOL. In contrast, among
      typically developing children, participation in vigorous activities during the
      school year was negatively correlated with school QOL. Finally, in both groups,
      participation in sedentary activities during school days was negatively
      correlated with school QOL. These results suggest that the parents' perceptions
      of their children's QOL may be related to the level of activeness of the leisure
      activities but also to temporal aspects. Therefore, it is important that
      therapists and educators consider the temporal aspects, when consulting with
      parents and their children regarding participation in leisure activities. 

PMID- 25589478
TI  - Reading comprehension in adolescents with ADHD: exploring the poor comprehender
      profile and individual differences in vocabulary and executive functions.
AB  - The overall objective of this study was to investigate reading comprehension in
      youth with and without a prior diagnosis of attention-deficit hyperactivity
      disorder (ADHD). The first goal was to determine whether youth with and without
      ADHD matched in word reading ability exhibited differences in reading
      comprehension proficiency. The next goal was to determine whether good and poor
      comprehenders within the ADHD subgroup differed from each other on language and
      academic achievement measures. The third objective was to examine whether word
      recognition or oral vocabulary knowledge mediated the effect of ADHD symptoms on
      reading comprehension performance. Youth with ADHD scored significantly lower
      than the comparison youth on a standardized measure of reading comprehension.
      Relative to good comprehenders with ADHD, poor comprehenders with ADHD exhibited
      weaknesses in expressive vocabulary, mathematical reasoning, written expression,
      and exhibited more executive function (EF) difficulties as reported by the
      teacher. Expressive vocabulary and word reading, but not teacher EF ratings,
      accounted for unique variance in reading comprehension performance and mediated
      the relationship between ADHD symptoms and reading comprehension. Implications
      for further research and educational practice are discussed. 

PMID- 25589479
TI  - Autofluorescence of Skin Advanced Glycation End Products: Marker of Metabolic
      Memory in Elderly Population.
AB  - BACKGROUND: Advanced glycation end products are involved in the vascular
      complications of diabetes, in chronic kidney disease, and in the aging process.
      Their accumulation in the elderly people, as reflected by skin autofluorescence
      (sAF), may be a marker of metabolic memory. We aimed to examine the association
      of sAF with glycemic and renal status 10 years earlier in older persons. METHODS:
      In retrospective cohort study, 328 elderly community dwellers aged of 75 years
      and over had sAF measurement 10 years after their inclusion in the Three-City
      cohort. Fasting plasma glucose and serum creatinine were measured at baseline and
      at 10-year follow-up. In 125 participants, HbA1c was available at these two
      times. Associations between sAF and the glycemic and renal status 10 years before
      were analyzed by multivariate linear regression adjusted for age, sex,
      hypertension, body mass index, hypertriglyceridemia, and smoking. RESULTS:
      Participants were 82.4 (standard deviation = 4.1) years on average, and their
      mean sAF was 2.8 (standard deviation = 0.7) arbitrary units (AU). After
      adjustment, sAF was higher in participants with long-standing diabetes (+0.38 AU,
      p = .01) or chronic kidney disease (+0.29 AU, p = .02) compared with healthy
      participants. sAF was related to fasting plasma glucose (+1 mmol/L associated
      with +0.08 AU, p = .01) and HbA1c (+1% associated with +0.15 AU, p = .03) 10
      years earlier, but not to the current fasting plasma glucose (p = .82) and HbA1c
      (p = .32). sAF was also related to the distal and current estimated glomerular
      filtration rates (p = .002 and .004, respectively). CONCLUSIONS: sAF reflects
      glycemic and renal status 10 years before, supporting its value as a marker of
      metabolic memory in the elderly people.

PMID- 25589480
TI  - Predicting speed at traffic lights--the problem with static assessments of
      frailty.

PMID- 25589481
TI  - Guideline treatment results in regression of atherosclerosis in type 2 diabetes
      mellitus.
AB  - BACKGROUND: Efficacy of guideline cardiovascular disease prevention regimens may
      differ between patients with or without type II diabetes mellitus. We therefore
      compared change in carotid artery wall dimensions in type II diabetes mellitus
      and non-type II diabetes mellitus patients with a history of a major
      cardiovascular disease event, using magnetic resonance imaging. METHODS: Thirty
      type II diabetes mellitus patients and 29 age- and sex-matched non-diabetes
      mellitus patients with a history of stroke or myocardial infarction and a carotid
      artery stenosis (15%-70%) were included. In all patients, treatment was according
      to cardiovascular risk management guidelines. At baseline and follow-up, carotid
      artery vessel wall dimensions were measured using 1.5 T magnetic resonance
      imaging. RESULTS: After 2 years of follow-up, total wall volume of the carotid
      artery in type II diabetes mellitus patients decreased by 9.6% (p = 0.016). In
      contrast, stabilization rather than regression of carotid artery wall dimensions
      was observed in non-diabetes mellitus patients over a 2-year period. Body mass
      index was identified as a predictor of total wall volume decrease. CONCLUSIONS:
      Guideline treatment arrests atherogenesis in non-diabetes mellitus patients and
      even decreases vessel wall dimensions in type II diabetes mellitus patients.
      Baseline body mass index predicts cardiovascular disease prevention efficacy
      expressed as decrease in total wall volume. These data emphasize the importance
      of optimal cardiovascular-prevention, particularly in diabetes patients with a
      high body mass index.

PMID- 25589483
TI  - Terrestrial basking sea turtles are responding to spatio-temporal sea surface
      temperature patterns.
AB  - Naturalists as early as Darwin observed terrestrial basking in green turtles
      (Chelonia mydas), but the distribution and environmental influences of this
      behaviour are poorly understood. Here, we examined 6 years of daily basking
      surveys in Hawaii and compared them with the phenology of local sea surface
      temperatures (SST). Data and models indicated basking peaks when SST is coolest,
      and we found this timeline consistent with bone stress markings. Next, we
      assessed the decadal SST profiles for the 11 global green turtle populations.
      Basking generally occurs when winter SST falls below 23 degrees C. From 1990 to
      2014, the SST for these populations warmed an average 0.04 degrees C yr(-1)
      (range 0.01-0.09 degrees C yr(-1)); roughly three times the observed global
      average over this period. Owing to projected future warming at basking sites, we
      estimated terrestrial basking in green turtles may cease globally by 2100. To
      predict and manage for future climate change, we encourage a more detailed
      understanding for how climate influences organismal biology. 

PMID- 25589484
TI  - A new mid-Silurian aquatic scorpion-one step closer to land?
AB  - One of the oldest known fossil scorpions, a new species from the mid-Silurian
      Eramosa Formation (430 myr) of Ontario, Canada, exhibits several surprising
      features. The depositional environment and associated biota indicate a marine
      habitat; however, the leg morphology of this scorpion, which has a short tarsus
      in common with all Recent scorpions, suggests that a key adaptation for
      terrestrial locomotion, the ability to support its weight on a subterminal
      'foot', appeared remarkably early in the scorpion fossil record. Specimens are
      preserved intact and undisturbed in a splayed posture typical of moults rather
      than carcasses. We postulate that these animals were aquatic, but occasionally
      ventured into extremely shallow water, or onto a transient subaerially exposed
      surface while moulting, before returning to deeper water. Shed exuviae were
      preserved in situ by rapid overgrowth of bacterial biofilm. 

PMID- 25589482
TI  - SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of
      ongoing outcome trials.
AB  - Given the multi-faceted pathogenesis of atherosclerosis in type 2 diabetes
      mellitus (T2DM), it is likely that interventions to mitigate this risk must
      address cardiovascular (CV) risk factors beyond glucose itself. Sodium glucose
      cotransporter-2 (SGLT-2) inhibitors are newer antihyperglycaemic agents with
      apparent multiple effects. Inherent in their mode of action to decrease glucose
      reabsorption by the kidneys by increasing urinary glucose excretion, these agents
      improve glycaemic control independent of insulin secretion with a low risk of
      hypoglycaemia. In this review, we outline those CV risk factors that this class
      appears to influence and provide the design features and trial characteristics of
      six ongoing outcome trials involving more than 41,000 individuals with T2DM.
      Those risk factors beyond glucose that can potentially be modulated positively
      with SGLT-2 inhibitors include blood pressure, weight, visceral adiposity,
      hyperinsulinaemia, arterial stiffness, albuminuria, circulating uric acid levels
      and oxidative stress. On the other hand, small increases in low-density
      lipoprotein (LDL)-cholesterol levels have also been observed for the class, which
      theoretically might offset some of these benefits. The potential translational
      impact of these effects is being tested with outcome trials, also reviewed in
      this article, powered to assess both macrovascular as well as certain
      microvascular outcomes in T2DM. These are expected to begin to report in late
      2015. 

PMID- 25589485
TI  - Ancestor-descendant relationships in evolution: origin of the extant pygmy right
      whale, Caperea marginata.
AB  - Ancestor-descendant relationships (ADRs), involving descent with modification,
      are the fundamental concept in evolution, but are usually difficult to recognize.
      We examined the cladistic relationship between the only reported fossil pygmy
      right whale, ?Miocaperea pulchra, and its sole living relative, the enigmatic
      pygmy right whale Caperea marginata, the latter represented by both adult and
      juvenile specimens. ?Miocaperea is phylogenetically bracketed between juvenile
      and adult Caperea marginata in morphologically based analyses, thus suggesting a
      possible ADR-the first so far identified within baleen whales (Cetacea:
      Mysticeti). The ?Miocaperea-Caperea lineage may show long-term morphological
      stasis and, in turn, punctuated equilibrium. 

PMID- 25589486
TI  - New partial skeletons of Palaeocene Nyctitheriidae and evaluation of proposed
      euarchontan affinities.
AB  - Small-bodied, insectivorous Nyctitheriidae are known in the Palaeogene fossil
      record almost exclusively from teeth and fragmentary jaws and have been referred
      to Eulipotyphla (shrews, moles and hedgehogs) based on dental similarities. By
      contrast, isolated postcrania attributed to the group suggest arboreality and a
      relationship to Euarchonta (primates, treeshrews and colugos). Cretaceous
      Palaeocene adapisoriculid insectivores have also been proposed as early
      euarchontans based on postcranial similarities. We describe the first known
      dentally associated nyctitheriid auditory regions and postcrania, and use them to
      test the proposed relationship to Euarchonta with cladistic analyses of 415
      dental, cranial and postcranial characteristics scored for 92 fossil and extant
      mammalian taxa. Although nyctitheriid postcrania share similarities with
      euarchontans likely related to arboreality, results of cladistic analyses suggest
      that nyctitheriids are closely related to Eulipotyphla. Adapisoriculidae is found
      to be outside of crown Placentalia. These results suggest that similarities in
      postcranial morphology among nyctitheriids, adapisoriculids and euarchontans
      represent separate instances of convergence or primitive retention of climbing
      capabilities. 

PMID- 25589487
TI  - Evidence for the buffer effect operating in multiple species at a national scale.
AB  - A long-standing aim of ecologists is to understand the processes involved in
      regulating populations. One such mechanism is the buffer effect, where lower
      quality habitats are increasingly used as a species reaches higher population
      densities, with a resultant average reduction in fecundity and survival limiting
      population growth. Although the buffer effect has been demonstrated in
      populations of a number of species, a test of its importance in influencing
      population growth rates of multiple species across large spatial scales is
      lacking. Here, we use habitat-specific population trends for 85 bird species from
      long-term national monitoring data (the UK Breeding Bird Survey) to examine its
      generality. We find that both patterns of population change and changes in
      habitat preference are consistent with the predictions of the buffer effect,
      providing support for its widespread operation. 

PMID- 25589488
TI  - The contribution of post-copulatory mechanisms to incipient ecological speciation
      in sticklebacks.
AB  - Ecology can play a major role in species diversification. As individuals are
      adapting to contrasting habitats, reproductive barriers may evolve at multiple
      levels. While pre-mating barriers have been extensively studied, the evolution of
      post-mating reproductive isolation during early stages of ecological speciation
      remains poorly understood. In diverging three-spined stickleback ecotypes from
      two lakes and two rivers, we observed differences in sperm traits between lake
      and river males. Interestingly, these differences did not translate into ecotype
      specific gamete precedence for sympatric males in competitive in vitro
      fertilization experiments, potentially owing to antagonistic compensatory
      effects. However, we observed indirect evidence for impeded development of inter
      ecotype zygotes, possibly suggesting an early stage of genetic incompatibility
      between ecotypes. Our results show that pre-zygotic post-copulatory mechanisms
      play a minor role during this first stage of ecotype divergence, but suggest that
      genetic incompatibilities may arise at early stages of ecological speciation. 

PMID- 25589489
TI  - The cost of migration: spoonbills suffer higher mortality during trans-Saharan
      spring migrations only.
AB  - Explanations for the wide variety of seasonal migration patterns of animals all
      carry the assumption that migration is costly and that this cost increases with
      migration distance. Although in some studies, the relationships between migration
      distance and breeding success or annual survival are established, none has
      investigated whether mortality during the actual migration increases with
      migration distance. Here, we compared seasonal survival between Eurasian
      spoonbills (Platalea leucorodia leucorodia) that breed in The Netherlands and
      migrate different distances (ca 1000, 2000 and 4500 km) to winter in France,
      Iberia and Mauritania, respectively. On the basis of resightings of individually
      marked birds throughout the year between 2005 and 2012, we show that summer,
      autumn and winter survival were very high and independent of migration distance,
      whereas mortality during spring migration was much higher (18%) for the birds
      that wintered in Mauritania, compared with those flying only as far as France
      (5%) or Iberia (6%). As such, this study is the first to show empirical evidence
      for increased mortality during some long migrations, likely driven by the
      presence of a physical barrier (the Sahara desert) in combination with suboptimal
      fuelling and unfavourable weather conditions en route. 

PMID- 25589490
TI  - Leaf P increase outpaces leaf N in an Inner Mongolia grassland over 27 years.
AB  - The dynamics of leaf nitrogen (N) and phosphorus (P) have been intensively
      explored in short-term experiments, but rarely at longer timescales. Here, we
      investigated leaf N : P stoichiometry over a 27-year interval in an Inner
      Mongolia grassland by comparing leaf N : P concentration of 2006 with that of
      1979. Across 80 species, both leaf N and P increased, but the increase in leaf N
      lagged behind that of leaf P, leading to a significant decrease in the N : P
      ratio. These changes in leaf N : P stoichiometry varied among functional groups.
      For leaf N, grasses increased, woody species tended to increase, whereas forbs
      showed no change. Unlike leaf N, leaf P of grasses and forbs increased, whereas
      woody species showed no change. Such changes may reflect N deposition and P
      release induced by soil acidification over the past decades. The interannual
      effect of precipitation may somewhat have reduced the soil available N, leading
      to the more modest increase of leaf N than of leaf P. Thus, leaf N : P
      stoichiometry significantly responded to long-term environmental changes in this
      temperate steppe, but different functional groups responded differently. Our
      results indicate that conclusions of plant stoichiometry under short-term N
      fertilization should be treated with caution when extrapolating to longer
      timescales. 

PMID- 25589492
TI  - Synergistic Blockade of EGFR and HER2 by New-Generation EGFR Tyrosine Kinase
      Inhibitor Enhances Radiation Effect in Bladder Cancer Cells.
AB  - Blockade of EGFR has been proved useful in enhancing the effect of radiotherapy,
      but the advantages of new-generation EGFR tyrosine kinase inhibitors (TKI) in
      radiosensitization are not well known. We used two human bladder cancer cells
      with wild-type EGFR to study the synergism between irradiation and afatinib (an
      EGFR/HER2 dual kinase inhibitor) or erlotinib (an EGFR kinase inhibitor). Here,
      we showed that afatinib has better radiosensitizing effect than erlotinib in
      increasing cancer cell killing, the percentage of apoptotic cells, and DNA
      damage. Afatinib is also superior to erlotinib in combining radiation to decrease
      tumor size, inhibit glucose metabolism, and enhance apoptotic proteins in vivo.
      Finally, erlotinib suppressed cell growth and induced more DNA damage in bladder
      cancer cells transfected with HER2 shRNA, but not in control vector-treated
      cells. In conclusion, concomitant blockade of radiation-activated EGFR and HER2
      signaling by a new-generation EGFR TKI better inhibits the growth of bladder
      cancer cells both in vitro and in vivo. The absence of radiosensitization by EGFR
      inhibition alone and the greater radiosensitizing effect of EGFR inhibitor in
      HER2 knocked down cells suggest the synergism between HER2 and EGFR in
      determining radiosensitivity. The regained radiosensitizing activity of erlotinib
      implies that with proper HER2 inhibition, EGFR tyrosine kinase is still a
      potential target to enhance radiotherapy effect in these seemingly unresponsive
      bladder cancer cells.

PMID- 25589493
TI  - The Preclinical Profile of the Duocarmycin-Based HER2-Targeting ADC SYD985
      Predicts for Clinical Benefit in Low HER2-Expressing Breast Cancers.
AB  - SYD985 is a HER2-targeting antibody-drug conjugate (ADC) based on trastuzumab and
      vc-seco-DUBA, a cleavable linker-duocarmycin payload. To evaluate the therapeutic
      potential of this new ADC, mechanistic in vitro studies and in vivo patient
      derived xenograft (PDX) studies were conducted to compare SYD985 head-to-head
      with T-DM1 (Kadcyla), another trastuzumab-based ADC. SYD985 and T-DM1 had similar
      binding affinities to HER2 and showed similar internalization. In vitro
      cytotoxicity assays showed similar potencies and efficacies in HER2 3+ cell
      lines, but in cell lines with low HER2 expression, SYD985 was 3- to 50-fold more
      potent than T-DM1. In contrast with T-DM1, SYD985 efficiently induced bystander
      killing in vitro in HER2-negative (HER2 0) cells mixed with HER2 3+, 2+, or 1+
      cell lines. At pH conditions relevant for tumors, cathepsin-B cleavage studies
      showed efficient release of the active toxin by SYD985 but not by T-DM1. These in
      vitro data suggest that SYD985 might be a more potent ADC in HER2-expressing
      tumors in vivo, especially in low HER2-expressing and/or in heterogeneous tumors.
      In line with this, in vivo antitumor studies in breast cancer PDX models showed
      that SYD985 is very active in HER2 3+, 2+, and 1+ models, whereas T-DM1 only
      showed significant antitumor activity in HER2 3+ breast cancer PDX models. These
      properties of SYD985 may enable expansion of the target population to patients
      who have low HER2-expressing breast cancer, a patient population with still unmet
      high medical need.

PMID- 25589494
TI  - CD30 is a potential therapeutic target in malignant mesothelioma.
AB  - CD30 is a cytokine receptor belonging to the TNF superfamily (TNFRSF8) that acts
      as a regulator of apoptosis. The presence of CD30 antigen is important in the
      diagnosis of Hodgkin disease and anaplastic large cell lymphoma. There have been
      sporadic reports of CD30 expression in nonlymphoid tumors, including malignant
      mesothelioma. Given the remarkable success of brentuximab vedotin, an antibody
      drug conjugate directed against CD30 antigen, in lymphoid malignancies, we
      undertook a study to examine the incidence of CD30 in mesothelioma and to
      investigate the ability to target CD30 antigen in mesothelioma. Mesothelioma
      tumor specimens (N = 83) were examined for CD30 expression by IHC. Positive CD30
      expression was noted in 13 mesothelioma specimens, primarily those of epithelial
      histology. There was no significant correlation of CD30 positivity with tumor
      grade, stage, or survival. Examination of four mesothelioma cell lines (H28,
      H2052, H2452, and 211H) for CD30 expression by both FACS analysis and confocal
      microscopy showed that CD30 antigen localized to the cell membrane. Brentuximab
      vedotin treatment of cultured mesothelioma cells produced a dose-dependent
      decrease in cell growth and viability at clinically relevant concentrations. Our
      studies validate the presence of CD30 antigen in a subgroup of epithelial-type
      mesothelioma tumors and indicate that selected mesothelioma patients may derive
      benefit from brentuximab vedotin treatment.

PMID- 25589491
TI  - The circadian clock in skin: implications for adult stem cells, tissue
      regeneration, cancer, aging, and immunity.
AB  - Historically, work on peripheral circadian clocks has been focused on organs and
      tissues that have prominent metabolic functions, such as the liver, fat, and
      muscle. In recent years, skin has emerged as a model for studying circadian clock
      regulation of cell proliferation, stem cell functions, tissue regeneration,
      aging, and carcinogenesis. Morphologically, skin is complex, containing multiple
      cell types and structures, and there is evidence for a functional circadian clock
      in most, if not all, of its cell types. Despite the complexity, skin stem cell
      populations are well defined, experimentally tractable, and exhibit prominent
      daily cell proliferation cycles. Hair follicle stem cells also participate in
      recurrent, long-lasting cycles of regeneration: the hair growth cycles. Among
      other advantages of skin is a broad repertoire of available genetic tools
      enabling the creation of cell type-specific circadian mutants. Also, due to the
      accessibility of skin, in vivo imaging techniques can be readily applied to study
      the circadian clock and its outputs in real time, even at the single-cell level.
      Skin provides the first line of defense against many environmental and stress
      factors that exhibit dramatic diurnal variations such as solar ultraviolet (UV)
      radiation and temperature. Studies have already linked the circadian clock to the
      control of UVB-induced DNA damage and skin cancers. Due to the important role
      that skin plays in the defense against microorganisms, it also represents a
      promising model system to further explore the role of the clock in the regulation
      of the body's immune functions. To that end, recent studies have already linked
      the circadian clock to psoriasis, one of the most common immune-mediated skin
      disorders. Skin also provides opportunities to interrogate the clock regulation
      of tissue metabolism in the context of stem cells and regeneration. Furthermore,
      many animal species feature prominent seasonal hair molt cycles, offering an
      attractive model for investigating the role of the clock in seasonal organismal
      behaviors. 

PMID- 25589495
TI  - Syngeneic Murine Ovarian Cancer Model Reveals That Ascites Enriches for Ovarian
      Cancer Stem-Like Cells Expressing Membrane GRP78.
AB  - Patients with ovarian cancer are generally diagnosed at FIGO (International
      Federation of Gynecology and Obstetrics) stage III/IV, when ascites is common.
      The volume of ascites correlates positively with the extent of metastasis and
      negatively with prognosis. Membrane GRP78, a stress-inducible endoplasmic
      reticulum chaperone that is also expressed on the plasma membrane ((mem)GRP78) of
      aggressive cancer cells, plays a crucial role in the embryonic stem cell
      maintenance. We studied the effects of ascites on ovarian cancer stem-like cells
      using a syngeneic mouse model. Our study demonstrates that ascites-derived tumor
      cells from mice injected intraperitoneally with murine ovarian cancer cells (ID8)
      express increased (mem)GRP78 levels compared with ID8 cells from normal culture.
      We hypothesized that these ascites-associated (mem)GRP78(+) cells are cancer stem
      like cells (CSC). Supporting this hypothesis, we show that (mem)GRP78(+) cells
      isolated from murine ascites exhibit increased sphere forming and tumor
      initiating abilities compared with (mem)GRP78(-) cells. When the tumor
      microenvironment is recapitulated by adding ascites fluid to cell culture, ID8
      cells express more (mem)GRP78 and increased self-renewing ability compared with
      those cultured in medium alone. Moreover, compared with their counterparts
      cultured in normal medium, ID8 cells cultured in ascites, or isolated from
      ascites, show increased stem cell marker expression. Antibodies directed against
      the carboxy-terminal domain of GRP78: (i) reduce self-renewing ability of murine
      and human ovarian cancer cells preincubated with ascites and (ii) suppress a
      GSK3alpha-AKT/SNAI1 signaling axis in these cells. Based on these data, we
      suggest that (mem)GRP78 is a logical therapeutic target for late-stage ovarian
      cancer.

PMID- 25589496
TI  - Mechanism of Oncogenic Signal Activation by the Novel Fusion Kinase FGFR3
      BAIAP2L1.
AB  - Recent cancer genome profiling studies have identified many novel genetic
      alterations, including rearrangements of genes encoding FGFR family members.
      However, most fusion genes are not functionally characterized, and their
      potentials in targeted therapy are unclear. We investigated a recently discovered
      gene fusion between FGFR3 and BAI1-associated protein 2-like 1 (BAIAP2L1). We
      identified 4 patients with bladder cancer and 2 patients with lung cancer
      harboring the FGFR3-BAIAP2L1 fusion through PCR and FISH assay screens. To
      investigate the oncogenic potential of the fusion gene, we established an FGFR3
      BAIAP2L1 transfectant with Rat-2 fibroblast cells (Rat-2_F3-B). The FGFR3
      BAIAP2L1 fusion had transforming activity in Rat2 cells, and Rat-2_F3-B cells
      were highly tumorigenic in mice. Rat-2_F3-B cells showed in vitro and in vivo
      sensitivity in the selective FGFR inhibitor CH5183284/Debio 1347, indicating that
      FGFR3 kinase activity is critical for tumorigenesis. Gene signature analysis
      revealed that FGFR3-BAIAP2L1 activates growth signals, such as the MAPK pathway,
      and inhibits tumor-suppressive signals, such as the p53, RB1, and CDKN2A
      pathways. We also established Rat-2_F3-B-DeltaBAR cells expressing an FGFR3
      BAIAP2L1 variant lacking the Bin-Amphiphysin-Rvs (BAR) dimerization domain of
      BAIAP2L1, which exhibited decreased tumorigenic activity, FGFR3 phosphorylation,
      and F3-B-DeltaBAR dimerization, compared with Rat-2_F3-B cells. Collectively,
      these data suggest that constitutive dimerization through the BAR domain promotes
      constitutive FGFR3 kinase activation and is essential for its potent oncogenic
      activity.

PMID- 25589498
TI  - Synthesis of lysozyme-metallacarborane conjugates and the effect of boron cluster
      modification on protein structure and function.
AB  - Two complementary methods, "in solution" and "in solid state", for the synthesis
      of lysozyme modified with metallacarborane (cobalt bis(dicarbollide), Co(C2 B9
      H11 )2 (2-) ) were developed. As metallacarborane donors, oxonium adducts of
      cobalt bis(dicarbollide) and 1,4-dioxane or tetrahydropyran were used. The
      physicochemical and biochemical properties of the obtained lysozyme
      metallacarborane conjugates were studied for changes in secondary and tertiary
      structure, aggregation behavior, and biological activity. Only minor changes in
      primary, secondary, and tertiary protein structure were observed, caused by the
      single substitution of metallacarborane on lysozyme. However, the modification
      produced significant changes in lysozyme enzymatic activity and a tendency toward
      time- and temperature-dependent aggregation. 

PMID- 25589497
TI  - A Combinatory Strategy for Detection of Live CTCs Using Microfiltration and a New
      Telomerase-Selective Adenovirus.
AB  - Circulating tumor cells (CTC) have become an important biomarker for early cancer
      diagnosis, prognosis, and treatment monitoring. Recently, a replication-competent
      recombinant adenovirus driven by a human telomerase gene (hTERT) promoter was
      shown to detect live CTCs in blood samples of patients with cancer. Here, we
      report a new class of adenoviruses containing regulatory elements that repress
      the hTERT gene in normal cells. Compared with the virus with only the hTERT core
      promoter, the new viruses showed better selectivity for replication in cancer
      cells than in normal cells. In particular, Ad5GTSe, containing three extra copies
      of a repressor element, displayed a superior tropism for cancer cells among
      leukocytes and was thus selected for CTC detection in blood samples. To further
      improve the efficiency and specificity of CTC identification, we tested a
      combinatory strategy of microfiltration enrichment using flexible micro spring
      arrays and Ad5GTSe imaging. Our experiments showed that this method efficiently
      detected both cancer cells spiked into healthy blood and potential CTCs in blood
      samples of patients with breast and pancreatic cancer, demonstrating its
      potential as a highly sensitive and reliable system for detection and capture of
      CTCs of different tumor types.

PMID- 25589499
TI  - Two decades of the oncologist.

PMID- 25589500
TI  - Adjuvant therapy-related shortening of survival (ATRESS): an underrated
      phenomenon.

PMID- 25589501
TI  - In reply.

PMID- 25589502
TI  - Doubling sensitivity in solids NMR: a simple and economical procedure for
      compressing samples.

PMID- 25589504
TI  - Application of an ultraminiature thermal neutron monitor for irradiation field
      study of accelerator-based neutron capture therapy.
AB  - Phantom experiments to evaluate thermal neutron flux distribution were performed
      using the Scintillator with Optical Fiber (SOF) detector, which was developed as
      a thermal neutron monitor during boron neutron capture therapy (BNCT)
      irradiation. Compared with the gold wire activation method and Monte Carlo N
      particle (MCNP) calculations, it was confirmed that the SOF detector is capable
      of measuring thermal neutron flux as low as 10(5) n/cm(2)/s with sufficient
      accuracy. The SOF detector will be useful for phantom experiments with BNCT
      neutron fields from low-current accelerator-based neutron sources. 

PMID- 25589503
TI  - Difference in distant failure site between locally advanced squamous cell
      carcinoma and adenocarcinoma of the uterine cervix after C-ion RT.
AB  - We investigated the first site of distant failure after carbon ion radiotherapy
      (C-ion RT) for locally advanced cervical cancer in three clinical trials. A total
      of 91 cases were enrolled in the three trials (Protocol 9702, 9704 and 9902).
      Histologically, 36 cases had squamous cell carcinoma (SqCC) and 55 cases had
      adenocarcinoma (AC), including 13 with adenosquamous cell carcinoma. The number
      of cases with Stage IIB, IIIB and IVA disease was 21, 59 and 11, respectively. Of
      the 91 cases, 42 had positive pelvic lymph nodes (PLNs). The median tumor size
      was 6.0 cm (range, 3.0-12.0 cm). The median follow-up duration for all cases was
      40 months (range, 7-181 months). A total of 40 cases developed distant failure as
      the first site of failure: 13 of 36 (36.1%) SqCC cases had distant failure, with
      9 of them with para-aortic lymph node (PALN) failure; 27 of 55 (44.0%) AC cases
      had distant failure, and 23 of them had distant failure excluding PALN
      metastasis. Distant failure rates of SqCC cases who had positive and negative
      PLNs before C-ion RT were 61.1% and 11.1%, respectively (P = 0.0045). Those of AC
      cases were 54.2% and 45.2%, respectively (P = 0.507). In conclusion, there were
      high rates of distant failure after C-ion RT in AC cases regardless of PLN
      status, and there were high rates of distant failure after C-ion RT, especially
      PALN failure, in SqCC cases with positive PLNs.

PMID- 25589506
TI  - Structural investigation of the high spin->low spin relaxation dynamics of the
      porous coordination network [Fe(pz)Pt(CN)4]?2.6 H2O.
AB  - The Hoffman-type coordination compound [Fe(pz)Pt(CN)4]?2.6 H2O (pz = pyrazine)
      shows a cooperative thermal spin transition at around 270 K. Synchrotron powder X
      Ray diffraction studies reveal that a quantitative photoinduced conversion from
      the low-spin (LS) state into the high-spin (HS) state, based on the light-induced
      excited spin-state trapping effect, can be achieved at 10 K in a microcrystalline
      powder. Time-resolved measurements evidence that the HS->LS relaxation proceeds
      by a two-step mechanism: a random HS->LS conversion at the beginning of the
      relaxation is followed by a nucleation and growth process, which proceeds until a
      quantitative HS->LS transformation has been reached.

PMID- 25589505
TI  - Assessment of transposed ovarian movement: how much of a safety margin should be
      added during pelvic radiotherapy?
AB  - The purpose of this study was to analyze transposed ovarian movement. Data from
      27 patients who underwent ovarian transposition after surgical treatment for
      uterine cancer were retrospectively analyzed. Computed tomography (CT) images
      including transposed ovaries were superimposed on other CT images acquired at
      different times, and were matched on bony structures. Differences in ovarian
      position between the CT images were measured. The planning organ at risk volume
      (PRV) margins were calculated from the formula of the 90% reference intervals
      (RIs) and the 95% RI, which were defined as mean +/- 1.65 standard deviation (SD)
      and mean +/- 1.96 SD, respectively. The 90% RI in the cranial, caudal, anterior,
      posterior, left and right directions were 1.5, 1.5, 1.4, 1.0, 1.7 and 0.9 cm,
      respectively. The 95% RI in the corresponding directions were 1.5, 2.0, 1.7, 1.2,
      1.9 and 1.2 cm, respectively. These data suggest that bilateral ovaries need a
      PRV margin of ~2 cm in all directions. The present study suggests that a
      transposed ovary needs the same PRV margin as a normal ovary (~2 cm). Even after
      transposition, ovaries should be kept away from the radiation field to take into
      consideration the degree of ovarian movement. 

PMID- 25589507
TI  - The tissue distribution of lipoprotein lipase determines where chylomicrons bind.
AB  - To determine the role of LPL for binding of lipoproteins to the vascular
      endothelium, and for the distribution of lipids from lipoproteins, four lines of
      induced mutant mice were used. Rat chylomicrons labeled in vivo with [(14)C]oleic
      acid (primarily in TGs, providing a tracer for lipolysis) and [(3)H]retinol
      (primarily in ester form, providing a tracer for the core lipids) were injected.
      TG label was cleared more rapidly than core label. There were no differences
      between the mouse lines in the rate at which core label was cleared. Two minutes
      after injection, about 5% of the core label, and hence chylomicron particles,
      were in the heart of WT mice. In mice that expressed LPL only in skeletal muscle,
      and had much reduced levels of LPL in the heart, binding of chylomicrons was
      reduced to 1%, whereas in mice that expressed LPL only in the heart, the binding
      was increased to over 10%. The same patterns of distribution were evident at 20
      min when most of the label had been cleared. Thus, the amount of LPL expressed in
      muscle and heart governed both the binding of chylomicron particles and the
      assimilation of chylomicron lipids in the tissue. 

PMID- 25589508
TI  - A robust all-atom model for LCAT generated by homology modeling.
AB  - LCAT is activated by apoA-I to form cholesteryl ester. We combined two
      structures, phospholipase A2 (PLA2) that hydrolyzes the ester bond at the sn-2
      position of oxidized (short) acyl chains of phospholipid, and bacteriophage
      tubulin PhuZ, as C- and N-terminal templates, respectively, to create a novel
      homology model for human LCAT. The juxtaposition of multiple structural motifs
      matching experimental data is compelling evidence for the general correctness of
      many features of the model: i) The N-terminal 10 residues of the model, required
      for LCAT activity, extend the hydrophobic binding trough for the sn-2 chain 15-20
      A relative to PLA2. ii) The topography of the trough places the ester bond of the
      sn-2 chain less than 5 A from the hydroxyl of the catalytic nucleophile, S181.
      iii) A beta-hairpin resembling a lipase lid separates S181 from solvent. iv) S181
      interacts with three functionally critical residues: E149, that regulates sn-2
      chain specificity, and K128 and R147, whose mutations cause LCAT deficiency.
      Because the model provides a novel explanation for the complicated thermodynamic
      problem of the transfer of hydrophobic substrates from HDL to the catalytic triad
      of LCAT, it is an important step toward understanding the antiatherogenic role of
      HDL in reverse cholesterol transport. 

PMID- 25589510
TI  - Abnormal differentiation of dental pulp cells in cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is a skeletal dysplasia caused by heterozygous
      mutations of RUNX2, a gene that is essential for the mineralization of bone and
      tooth. We isolated primary dental pulp cells from a 10-y-old patient and tested
      their proliferative capacity, alkaline phosphatase activity, and ability to form
      mineralized nodules, in comparison with those from 7 healthy children. All these
      measures were reduced in primary dental pulp cells from the CCD patient. The
      expression of the osteoblast/odontoblast-associated genes RUNX2, ALP, OCN, and
      DSPP was also found to be significantly decreased in the primary dental pulp
      cells of the CCD patient. The osteoclast-related markers TRAP, CTSK, CTR, and
      MMP9 were decreased in primary dental pulp cells cocultured with human peripheral
      blood mononuclear cells. Moreover, the expression of RANKL and the ratio of
      RANKL/OPG were both reduced in the cells from the CCD patient, indicating that
      the RUNX2 mutation interfered with the bone-remodeling pathway and decreased the
      capacity of primary dental pulp cells to support osteoclast differentiation.
      These effects may be partly responsible for the defects in tooth development and
      the retention of primary teeth that is typical of CCD. 

PMID- 25589512
TI  - PPARgamma/mTOR signalling: striking the right balance in cartilage homeostasis.

PMID- 25589511
TI  - Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a
      multicentre, randomised, double-blind, non-inferiority trial versus celecoxib.
AB  - OBJECTIVES: To compare the efficacy and safety of chondroitin sulfate plus
      glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee
      osteoarthritis and severe pain. METHODS: Double-blind Multicentre Osteoarthritis
      interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and
      Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with
      Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-to-severe pain
      (Western Ontario and McMaster osteoarthritis index (WOMAC) score >=301; 0-500
      scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times
      a day or 200 mg celecoxib every day for 6 months. The primary outcome was the
      mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes
      included WOMAC function and stiffness, visual analogue scale for pain, presence
      of joint swelling/effusion, rescue medication consumption, Outcome Measures in
      Rheumatology Clinical Trials and Osteoarthritis Research Society International
      (OMERACT-OARSI) criteria and EuroQoL-5D. RESULTS: The adjusted mean change (95%
      CI) in WOMAC pain was -185.7 (-200.3 to -171.1) (50.1% decrease) with CS+GH and 
      186.8 (-201.7 to -171.9) (50.2% decrease) with celecoxib, meeting the non
      inferiority margin of -40: -1.11 (-22.0 to 19.8; p=0.92). All sensitivity
      analyses were consistent with that result. At 6 months, 79.7% of patients in the
      combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI
      criteria. Both groups elicited a reduction >50% in the presence of joint
      swelling; a similar reduction was seen for effusion. No differences were observed
      for the other secondary outcomes. Adverse events were low and similarly
      distributed between groups. CONCLUSIONS: CS+GH has comparable efficacy to
      celecoxib in reducing pain, stiffness, functional limitation and joint
      swelling/effusion after 6 months in patients with painful knee osteoarthritis,
      with a good safety profile. TRIAL REGISTRATION NUMBER: NCT01425853.

PMID- 25589514
TI  - Lymphocytic focus score as a prognostic tool.

PMID- 25589513
TI  - Suppression of monosodium urate crystal-induced cytokine production by butyrate
      is mediated by the inhibition of class I histone deacetylases.
AB  - OBJECTIVES: Acute gouty arthritis is caused by endogenously formed monosodium
      urate (MSU) crystals, which are potent activators of the NLRP3 inflammasome.
      However, to induce the release of active interleukin (IL)-1beta, an additional
      stimulus is needed. Saturated long-chain free fatty acids (FFAs) can provide such
      a signal and stimulate transcription of pro-IL-1beta. In contrast, the short
      chain fatty acid butyrate possesses anti-inflammatory effects. One of the
      mechanisms involved is inhibition of histone deacetylases (HDACs). Here, we
      explored the effects of butyrate on MSU+FFA-induced cytokine production and its
      inhibition of specific HDACs. METHODS: Freshly isolated peripheral blood
      mononuclear cells (PBMCs) from healthy donors were stimulated with MSU and
      palmitic acid (C16.0) in the presence or absence of butyrate or a synthetic HDAC
      inhibitor. Cytokine responses were measured with ELISA and quantitative PCR. HDAC
      activity was measured with fluorimetric assays. RESULTS: Butyrate decreased
      C16.0+MSU-induced production of IL-1beta, IL-6, IL-8 and IL-1beta mRNA in PBMCs
      from healthy donors. Similar results were obtained in PBMCs isolated from
      patients with gout. Butyrate specifically inhibited class I HDACs. The HDAC
      inhibitor, panobinostat and the potent HDAC inhibitor, ITF-B, also decreased ex
      vivo C16.0+MSU-induced IL-1beta production. CONCLUSIONS: In agreement with the
      reported low inhibitory potency of butyrate, a high concentration was needed for
      cytokine suppression, whereas synthetic HDAC inhibitors showed potent anti
      inflammatory effects at nanomolar concentrations. These novel HDAC inhibitors
      could be effective in the treatment of acute gout. Moreover, the use of specific
      HDAC inhibitors could even improve the efficacy and reduce any potential adverse
      effects.

PMID- 25589515
TI  - Activating transcription factor 3 regulates canonical TGFbeta signalling in
      systemic sclerosis.
AB  - BACKGROUND: Activating transcription factor 3 (ATF3), a member of the ATF/cAMP
      responsive element binding (CREB) family of transcription factors, regulates
      cellular response to stress including oxidative stress. The aim of this study was
      to analyse the role of ATF3 in fibroblast activation in systemic sclerosis (SSc).
      METHODS: ATF3 was analysed by reverse transcription quantitative PCR, western
      blot and immunohistochemistry. ATF3 knockout fibroblasts and mice were used to
      study the functional role of ATF3. Knockdown experiments, reporter assays and
      coimmunoprecipitation were performed to study the effects of ATF3 on Smad and
      activation protein 1 (AP-1) signalling. The role of c-Jun was analysed by
      costaining, specific inactivation and coimmunoprecipitation. RESULTS:
      Transforming growth factor-beta (TGFbeta) upregulates the expression of ATF3 in
      SSc fibroblasts. ATF3-deficient fibroblasts were less sensitive to TGFbeta,
      whereas ectopic expression of ATF3 enhanced the profibrotic effects of TGFbeta.
      Mechanistically, ATF3 interacts with Smad3 directly on stimulation with TGFbeta
      and regulates Smad activity in a c-Jun-dependent manner. Knockout of ATF3
      protected mice from bleomycin-induced fibrosis and fibrosis induced by
      overexpression of a constitutively active TGFbeta receptor I. Reporter assays and
      analyses of the expression of Smad target genes demonstrated that binding of ATF3
      regulates the transcriptional activity of Smad3. CONCLUSIONS: We demonstrate for
      the first time a key role for ATF3 in fibrosis. Knockout of the ATF3 gene reduced
      the stimulatory effect of TGFbeta on fibroblasts by interfering with canonical
      Smad signalling and protected the mice from experimental fibrosis in two
      different models. ATF3 might thus be a candidate for molecular targeted therapies
      for SSc.

PMID- 25589518
TI  - Electronic cigarettes: reasons to be cautious.

PMID- 25589516
TI  - Immune cells and preterm labour: do invariant NKT cells hold the key?

PMID- 25589519
TI  - Functional brain imaging in respiratory medicine.
AB  - Discordance of clinical symptoms with markers of disease severity remains a
      conundrum in a variety of respiratory conditions. The breathlessness of chronic
      lung disease correlates poorly with spirometry, yet is a better predictor of
      mortality. In chronic cough, symptoms are often evident without clear physical
      cause. In asthma, the terms 'over perceivers' and 'under perceivers' are common
      parlance. In all these examples, aberrant brain mechanisms may explain the
      mismatch between symptoms and pathology. Functional MRI is a non-invasive method
      of measuring brain function. It has recently become significantly advanced enough
      to be useful in clinical research and to address these potential mechanisms. This
      article explains how FMRI works, current understanding from FMRI in
      breathlessness, cough and asthma and suggests possibilities for future research. 

PMID- 25589517
TI  - Activation of decidual invariant natural killer T cells promotes
      lipopolysaccharide-induced preterm birth.
AB  - Invariant natural killer T (iNKT) cells are crucial for host defense against a
      variety of microbial pathogens, but the underlying mechanisms of iNKT cells
      activation by microbes are not fully explained. In this study, we investigated
      the molecular mechanisms of iNKT cell activation in lipopolysaccharide (LPS)
      stimulated preterm birth using an adoptive transfer system and diverse
      neutralizing antibodies (Abs) and inhibitors. We found that adoptive transfer of
      decidual iNKT cells to LPS-stimulated iNKT cell deficient Jalpha18(-/-) mice that
      lack invariant Valpha14Jalpha281T cell receptor (TCR) expression significantly
      decreased the time to delivery and increased the percentage of decidual iNKT
      cells. Neutralizing Abs against Toll-like receptor 4 (TLR-4), CD1d, interleukin
      (IL)-12 and IL-18, and inhibitors blocking the activation of nuclear factor
      kappaB (NF-kappaB), mitogen-activated protein kinase (MAPK) p38 and extracellular
      signal-regulated kinase (ERK) significantly reduced in vivo percentages of
      decidual iNKT cells, their intracellular interferon (IFN)-gamma production and
      surface CD69 expression. In vitro, in the presence of the same Abs and inhibitors
      used as in vivo, decidual iNKT cells co-cultured with LPS-pulsed dendritic cells
      (DCs) showed significantly decreased extracellular and intracellular IFN-gamma
      secretion and surface CD69 expression. Our data demonstrate that the activation
      of decidual iNKT cells plays an important role in inflammation-induced preterm
      birth. Activation of decidual iNKT cells also requires TLR4-mediated NF-kappaB,
      MAPK p38 and ERK pathways, the proinflammatory cytokines IL-12 and IL-18, and
      endogenous glycolipid antigens presented by CD1d. 

PMID- 25589520
TI  - An alternative framework to investigating and understanding intraindividual
      processes in substance abuse recovery: an idiographic approach and demonstration.
AB  - BACKGROUND: Sustained recovery from substance abuse is a dynamic intraindividual
      level process. OBJECTIVES: We argue that research on recovery process will
      benefit from a theoretical approach that captures both the dynamic and the
      idiographic nature of substance abuse recovery. In addition to setting out why we
      believe that research on recovery can benefit from such an approach, we provide a
      demonstration of idiographic within-individual analyses of between- and within
      day associations among negative affect, substance use craving, and positive
      social experiences. DESIGN AND SUBJECTS: The data used were drawn from 39
      abstinent young adults in 12-step recovery from substance abuse (mean age = 22.9,
      females = 12). Participants provided an average of 26.7 days of daily diary data
      by end-of-day collections. Unified first-order structural equation models were
      fit individually to predict daily levels of craving and negative affect from the
      previous day's same two variables as well as from both the previous day's and the
      same day's positive social experiences. RESULTS: Model estimates demonstrated
      substantial interindividual heterogeneity in their day-to-day associations in
      both direction and magnitude, highlighting the importance of applying idiographic
      approach to understanding recovery. Cluster analyses were subsequently applied to
      individual model estimates to identify homogeneous subgroups that demonstrated
      similar day-to-day association patterns, revealing two distinct subgroups that
      appeared to manage daily abstinence through different mechanisms. CONCLUSIONS:
      The idiographic approach presented provides the potential value of framing
      recovery as an idiosyncratic dynamic process and provides targets for tailored
      and adaptive treatment and recovery supporting intervention in future design and
      evaluation.

PMID- 25589521
TI  - Extrafloral-nectar-based partner manipulation in plant-ant relationships.
AB  - Plant-ant interactions are generally considered as mutualisms, with both parties
      gaining benefits from the association. It has recently emerged that some of these
      mutualistic associations have, however, evolved towards other forms of
      relationships and, in particular, that plants may manipulate their partner ants
      to make reciprocation more beneficial, thereby stabilizing the mutualism.
      Focusing on plants bearing extrafloral nectaries, we review recent studies and
      address three key questions: (i) how can plants attract potential partners and
      maintain their services; (ii) are there compounds in extrafloral nectar that
      could mediate partner manipulation; and (iii) are ants susceptible to such
      compounds? After reviewing the current knowledge on plant-ant associations, we
      propose a possible scenario where plant-derived chemicals, such as secondary
      metabolites, known to have an impact on animal brain, could have evolved in
      plants to attract and manipulate ant behaviour. This new viewpoint would place
      plant-animal interaction in a different ecological context, opening new
      ecological and neurobiological perspectives of drug seeking and use. 

PMID- 25589523
TI  - Understanding Patients' Preferences for Referrals to Specialists for an
      Asymptomatic Condition.
AB  - BACKGROUND: A specialty referral is a common but complex decision that often
      requires a primary care provider to balance his or her own interests with those
      of the patient. OBJECTIVE: To examine the factors that influence a patient's
      choice of a specialist for consultation for an asymptomatic condition and better
      understand the tradeoffs that patients are and are not willing to make in this
      decision. DESIGN: Stratified cross-sectional convenience sample of subjects
      selected to parallel US population demographics. PARTICIPANTS: Members of an
      Internet survey panel who reported seeing a physician in the past year whose
      responses met objective quality metrics for attention. MAIN MEASURES: Respondents
      completed an adaptive conjoint analysis survey comparing specialists regarding
      eight attributes. The reliability of assessments and the predictive validity of
      models were measured using holdout samples. The relative importance (RI) of
      different attributes was computed using paired t tests. The implications of
      utility values were studied using market simulation methods. KEY RESULTS: Five
      hundred and thirty subjects completed the survey and had responses that met
      quality criteria. The reliability of responses was high (86% agreement), and
      models were predictive of patients' preferences (82.6% agreement with holdout
      choices). The most important attribute for patients was out-of-pocket cost (RI of
      19.5%, P < 0.0001 v. other factors). Among the nonfinancial factors,
      "collaboration and communication" with the primary care provider was the most
      important attribute (RI of 13.1% P < 0.001). Third in importance was whether the
      specialist practiced shared decision making (RI of 12.2% P < 0.001 v. other
      factors except delay in consultation). Cost did not dominate decision making. In
      market simulations, patients frequently preferred more expensive providers. For
      example, most patients (76.3%) were willing to pay more ($80) to see a specialist
      who both collaborated well with their primary care provider and practiced shared
      decision making. Most patients prefer to wait for a doctor who practices shared
      decision making: Only one-third (32.3%) of patients preferred a paternalistic
      doctor who was available in 2 weeks over a doctor who practiced decision making
      but was available in 4 weeks. CONCLUSIONS: In the setting of a referral for an
      asymptomatic but serious condition, out-of-pocket costs are important to
      patients; however, they also value specialists who collaborate and communicate
      well with their primary care providers and who practice shared decision making.
      Patients have wide variability in preferences for specialists, and referral
      decisions should be individualized.

PMID- 25589524
TI  - Graphical representation of life paths to better convey results of decision
      models to patients.
AB  - The inclusion of patients' perspectives in clinical practice has become an
      important matter for health professionals, in view of the increasing attention to
      patient-centered care. In this regard, this report illustrates a method for
      developing a visual aid that supports the physician in the process of informing
      patients about a critical decisional problem. In particular, we focused on
      interpretation of the results of decision trees embedding Markov models
      implemented with the commercial tool TreeAge Pro. Starting from patient-level
      simulations and exploiting some advanced functionalities of TreeAge Pro, we
      combined results to produce a novel graphical output that represents the
      distributions of outcomes over the lifetime for the different decision options,
      thus becoming a more informative decision support in a context of shared decision
      making. The training example used to illustrate the method is a decision tree for
      thromboembolism risk prevention in patients with nonvalvular atrial fibrillation.

PMID- 25589525
TI  - Value of Genetic Testing for Hereditary Colorectal Cancer in a Probability-Based
      US Online Sample.
AB  - BACKGROUND: . While choices about genetic testing are increasingly common for
      patients and families, and public opinion surveys suggest public interest in
      genomics, it is not known how adults from the general population value genetic
      testing for heritable conditions. We sought to understand in a US sample the
      relative value of the characteristics of genetic tests to identify risk of
      hereditary colorectal cancer, among the first genomic applications with evidence
      to support its translation to clinical settings. METHODS: . A Web-enabled choice
      format conjoint survey was conducted with adults age 50 years and older from a
      probability-based US panel. Participants were asked to make a series of choices
      between 2 hypothetical blood tests that differed in risk of false-negative test,
      privacy, and cost. Random parameters logit models were used to estimate
      preferences, the dollar value of genetic information, and intent to have genetic
      testing. RESULTS: . A total of 355 individuals completed choice-format questions.
      Cost and privacy were more highly valued than reducing the chance of a false
      negative result. Most (97% [95% confidence interval (CI)], 95%-99%) would have
      genetic testing to reduce the risk of dying of colorectal cancer in the best
      scenario (no false negatives, results disclosed to primary care physician). Only
      41% (95% CI, 25%-57%) would have genetic testing in the worst case (20% false
      negatives, results disclosed to insurance company). CONCLUSIONS: . Given the
      characteristics and levels included in the choice, if false-negative test results
      are unlikely and results are shared with a primary care physician, the majority
      would have genetic testing. As genomic services become widely available, primary
      care professionals will need to be increasingly knowledgeable about genetic
      testing decisions.

PMID- 25589526
TI  - Oral squamous cell carcinoma in a patient treated with long-term pegylated
      liposomal doxorubicin for recurrent ovarian cancer.
AB  - We present a case of a woman who developed an oral squamous cell carcinoma (SCC)
      after being treated for a recurrent ovarian carcinoma with subtotal gastric
      resection and adjuvant pegylated liposomal doxorubicin (PLD). She received six
      cycles of PLD induction and maintenance therapy, which was continued for 5 years.
      She was free from disease at the following visits but 3 years later she developed
      SCC of her left inferior edentulous gums. The patient was negative for human
      papillomavirus and had never smoked in her life or had a history of alcohol use
      or any other environmental risk factors. PLD is known to accumulate in eccrine
      glands of the hands and the feet and in the oral mucosa, therefore causing skin
      toxicity and mucositis. It is conceivable that this specific biodistribution to
      the oral mucosa may be responsible for the onset of SCC.

PMID- 25589528
TI  - Rabies encephalitis in a child: a failure of rabies post exposure prophylaxis?
AB  - Rabies remains a serious public health problem in many developing countries. The
      diagnosis is easy when a non-immunised patient presents with hydrophobia and
      hypersalivation after a bite by a known rabid animal but more difficult when a
      patient presents atypical symptoms after having received rabies postexposure
      prophylaxis. Rabies postexposure prophylaxis failure is rare. We report a case of
      a 6-year-old boy who presented febrile seizure with agitation and cerebellar
      signs, without hydrophobia or hypersalivation, 17 days after a dog bite. Despite
      four doses of rabies vaccine and immunoglobulin, he died. Diagnostic confirmation
      of rabies encephalitis was made in post mortem on brain biopsies by fluorescent
      antibody technique.

PMID- 25589527
TI  - Airway compromise due to adenoid cystic carcinoma obstructing the distal trachea:
      a review of current management and clinical trials.
AB  - An 84-year-old man presented with a 2-month history of intermittent stridor and
      worsening difficulty in breathing. Chest X-ray and flexible nasendoscopy were
      unremarkable but following further deterioration a CT scan revealed an
      obstructing lesion in the distal trachea. Bronchoscopy revealed an infiltrative
      tumour arising 3 cm above the carina causing 90% obstruction. The mass was
      biopsied and surgically debrided to leave a patent airway. Histological analysis
      revealed a diagnosis of adenoid cystic carcinoma. Transthoracic surgical
      resection was unsuccessful and the patient continues to be effectively managed
      with periodic bronchoscopic debulking and radiotherapy. This case highlights the
      diagnostic and therapeutic dilemmas posed by distal tracheal lesions and the need
      for specialist input for effective management.

PMID- 25589529
TI  - An unusual parotid mass.
AB  - A 70-year-old Caucasian man with multiple comorbidities presented with a painless
      lump over the right parotid gland which was gradually increasing in size over the
      preceding 12 months. There were no systemic symptoms or facial weakness. Imaging
      indicated a benign tumour of the right parotid. Superficial parotidectomy was
      performed and the histology revealed a sialolipoma.

PMID- 25589530
TI  - Langerhans cell histiocytosis (LCH) of the mandible in an adult: a rare case.

PMID- 25589531
TI  - Enterobiasis: threadworm infection presenting as acute appendicitis in a 13-year
      old girl.

PMID- 25589532
TI  - Relationship between expression and methylation of obesity-related genes in
      children.
AB  - Epigenetic control of gene expression in children remains poorly understood, but
      new technologies can help elucidate the relationship between expression and DNA
      methylation. Here, we utilized the nCounter Analysis System to characterise the
      expression of 60 genes in 69 9-year-old children from a cohort with a high
      prevalence of obesity. nCounter expression levels ranged broadly (from 3 to over
      10000 messenger RNA counts) and were divided into four categories: high (>2000
      counts), moderate (200-1000 counts), low (100-200 counts) and marginal (<100
      counts). For a subset of five genes (ADIPOR1, PPARG1, GSTM1, PON1 and ACACA) from
      different expression level categories, we validated nCounter data using reverse
      transcription-polymerase chain reaction (RT-PCR), and expanded RT-PCR analysis of
      ADIPOR1 to include 180 children. Expression data from the two methodologies were
      correlated for all five genes included in the validation experiment, with
      estimates ranging from r s = 0.26 (P = 0.02) to r s = 0.88 (P < 5*10(-6)).
      ADIPOR1 and PPARG1 nCounter expression levels were negatively correlated (r = 
      0.60, P < 5*10(-5)), and this relationship was stronger in overweight children (r
      = -0.73, P < 5*10(-5)) than in normal weight children (r = -0.42, P = 0.016).
      Using methylation data from the Infinium HumanMethylation450 BeadChip (n = 180),
      we found eight CpG sites in ADIPOR1 and PPARG where methylation level was
      associated with expression by RT-PCR (P < 0.05). Hypomethylation of PPARG gene
      body site cg10499651 was associated with increased expression as measured by both
      RT-PCR and nCounter (P < 0.05). We found no statistically significant
      relationships between either expression or methylation of ADIPOR1 and PPARG and
      body mass index or waist circumference. In addition to demonstrating the validity
      of expression data derived from nCounter, our results illustrate the use of new
      technologies in assessing epigenetic effects on expression in children. 

PMID- 25589534
TI  - Abnormal stress-related measures of arterial stiffness in middle-aged and elderly
      men and women with impaired fasting glucose at risk for a first episode of
      symptomatic heart failure.
AB  - BACKGROUND: Abnormal resting arterial stiffness is present in middle-aged and
      elderly persons with abnormalities of fasting glucose (diabetes or impaired
      fasting glucose) and is associated with exercise intolerance. We sought to
      determine whether these same persons exhibited stress-related abnormalities of
      arterial stiffness. METHODS AND RESULTS: We analyzed dobutamine magnetic
      resonance stress imaging results from 373 consecutively recruited persons aged 55
      to 85 years with normal fasting glucose, impaired fasting glucose, or diabetes
      who were at risk for but without symptomatic heart failure. Personnel blinded to
      participant identifiers measured arterial stiffness (brachial pulse pressure/left
      ventricular stroke volume indexed to body surface area, the aortic elastance
      index [brachial end-systolic pressure/left ventricular stroke volume indexed to
      body surface area], and thoracic aortic distensibility) at 80% of the maximum
      predicted heart rate response for age. Participants averaged 69+/-8 years of age;
      79% were white, 92% were hypertensive, and 66% were women. After accounting for
      hypertension, sex, coronary artery disease, smoking, medications,
      hypercholesterolemia, and visceral fat, we observed an effect of glycemic status
      for stress measures of arterial stiffness in those with diabetes and impaired
      fasting glucose relative to those with normal fasting glucose (P=0.002, P=0.02,
      and P=0.003, respectively). CONCLUSION: Middle- and older-aged individuals with
      diabetes or impaired fasting glucose have higher stress measures of arterial
      stiffness than those with normal fasting glucose. These data emphasize the need
      for future studies with larger sample sizes to determine whether stress-related
      elevations in arterial stiffness are related to exercise intolerance and future
      episodes of heart failure experienced by those with abnormalities of fasting
      glucose. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/. Unique
      identifier: NCT00542503.

PMID- 25589537
TI  - Supratentorial ependymoma presenting as a cortical cyst with a mural nodule in an
      adult.
AB  - Supratentorial ependymoma is a rare tumour in the adult central nervous system.
      We present an unusual case of supratentorial ependymoma in a young adult that
      presented as a pure cortical cyst with a mural nodule and discuss the
      differential diagnosis of such lesions in the brain. 

PMID- 25589535
TI  - Resting heart rate and risk of incident heart failure: three prospective cohort
      studies and a systematic meta-analysis.
AB  - BACKGROUND: The relationship between resting heart rate (RHR) and incident heart
      failure (HF) has been questioned. METHODS AND RESULTS: RHR was assessed at
      baseline in 7073 participants in 3 prospective cohorts (Cardiovascular Health
      Study, Health ABC study and Kuopio Ischemic Heart Disease Study) that recorded
      1189 incident HF outcomes during 92 702 person-years of follow-up. Mean age of
      participants was 67 (9.9) years and mean RHR was 64.6 (11.1) bpm. Baseline RHR
      correlated (P<0.001) positively with body mass index (r=0.10), fasting glucose
      (r=0.18), and C-reactive protein (r=0.20); and inversely with serum creatinine
      (r=-0.05) and albumin (r=-0.05). Baseline RHR was non-linearly associated with HF
      risk. The age and sex-adjusted hazard ratio for HF comparing the top (>72 bpm)
      versus the bottom (<57 bpm) quartile of baseline RHR was 1.48 (95% confidence
      interval [CI] 1.26 to 1.74) and was modestly attenuated (1.30, 95% CI 1.10 to
      1.53) with further adjustment for body mass index, history of diabetes,
      hypertension, smoking status, serum creatinine, and left ventricular hypertrophy.
      These findings remained consistent in analyses accounting for incident coronary
      heart disease, excluding individuals with prior cardiovascular events, or those
      taking beta-blockers; and in subgroups defined by several individual participant
      characteristics. In a pooled random effects meta-analysis of 7 population-based
      studies (43 051 participants and 3476 HF events), the overall hazard ratio
      comparing top versus bottom fourth of RHR was 1.40 (95% CI: 1.19 to 1.64).
      CONCLUSIONS: There is a non-linear association between RHR and incident HF.
      Further research is needed to understand the physiologic foundations of this
      association.

PMID- 25589536
TI  - Comparison of heritability of Cystatin C- and creatinine-based estimates of
      kidney function and their relation to heritability of cardiovascular disease.
AB  - BACKGROUND: Decreased renal function is an established risk factor for
      cardiovascular disease (CVD). Causal mechanisms between estimates of renal
      function and CVD are intricate and investigation of the relative importance of
      genetic and environmental factors for the variability of these phenotypes could
      provide new knowledge. METHODS AND RESULTS: Cystatin C and creatinine levels in
      12 313 twins were analyzed. Uni- and bivariate heritability for these traits and
      CVD was estimated through structured equation modelling and genome-wide complex
      trait analysis (GCTA) in order to independently confirm additive genetic effects.
      Twin model-estimated heritability of Cystatin C was 0.55 (95% confidence interval
      [CI], 0.49 to 0.60) in men, 0.63 (0.59 to 0.66) in women, and 0.60 (0.56 to 0.63)
      in both sexes combined. For creatinine, heritability estimates were in the same
      range. Heritability of CVD was 0.39 (0.02 to 0.67) in men and 0.20 (0.00 to 0.61)
      in women. The phenotypic correlation between Cystatin C and CVD correlation was
      0.16 (0.12 to 0.20) in men and 0.17 (0.13 to 0.21) in women, whereas the genetic
      correlation in males was 0.41 (0.21 to 0.62) while it was non-significant in
      females. Trough GCTA, the heritability of Cystatin C and creatinine in both sexes
      combined was estimated to 0.40 (SE 0.07, P=8E(-9)) and 0.19 (SE 0.07, P=0.003),
      respectively. CONCLUSIONS: Twin model-based heritability of Cystatin C was higher
      compared to previous studies. Co-variation between Cystatin C and CVD in males
      was partly explained by additive genetic components, indicating that Cystatin C
      and CVD share genetic influences. The GCTA provided independent evidence for
      significant contribution of additive genetics to trait variance of Cystatin C.

PMID- 25589538
TI  - An 18-year-old woman with a 34-cm metaplastic breast carcinoma.
AB  - Metaplastic breast carcinomas (MBCs) are rare malignancies usually with poor
      prognosis. We report a case of an 18-year-old African female patient who
      presented with a 34-cm tumor on the right breast. Biopsy showed an extensively
      necrotic MBC negative for estrogen receptor, progesterone receptor and human
      epidermal growth factor receptor 2 (triple negative). A modified right radical
      mastectomy was performed, followed by adjuvant chemotherapy. Histology confirmed
      a widely necrotic undifferentiated malignant tumor, with strong and diffuse
      expression of vimentin and B-cell lymphoma 2, focal high-molecular-weight
      keratins and focal CD34 expression; Ki67 was >90%. There was no skin, deep margin
      or lymph node involvement. Six months after surgery, the patient showed a 9 * 7
      cm nodule adjacent to the suture and adherent to the anterior chest wall. The
      tumor was considered unresectable and the patient evolved with rapid systemic
      deterioration. The patient had a progression-free survival of 6 months and
      overall survival of 9 months. 

PMID- 25589539
TI  - A simple case of gallstone ileus?
AB  - A 68-year-old gentleman presented with abdominal distension and faeculent
      vomiting. He had a background of cerebral palsy with learning difficulties making
      history taking problematic. A CT scan suggested small bowel obstruction secondary
      to gallstone ileus. The most likely differential diagnosis was an inguinal hernia
      which was noted adjacent to the transition point. Laparotomy revealed grossly
      dilated small bowel with a 3-cm intraluminal gallstone. The gallstone was freely
      mobile within the lumen on the ileum and thus could not be causing obstruction. A
      caecal mass was also found, which was determined to be the cause of the
      obstruction. Limited ileocaecectomy was performed, which revealed a Duke's A
      adenocarcinoma. Gallstone ileus and caecal tumour can commonly be confused prior
      to surgery. There are however no previous reports of concurrent gallstone ileus
      and caecal tumour. Communication issues with the patient are likely to have
      contributed to the difficulty in diagnosis. 

PMID- 25589540
TI  - Perforation of the splenic flexure of the colon by an ingested wooden toothpick.
AB  - We present the case of a 23-year-old man who consulted in the emergency
      department 6 days after ingesting a wooden toothpick with features of a localized
      peritonitis in the left upper quadrant of the abdomen. Surgical exploration
      revealed a perforation of the splenic flexure of the colon by the toothpick
      during its migration. This rare case is analysed in the light of the current
      literature. There is need for a greater awareness about the dangers of a
      swallowed toothpick. It is advisable to always trace the toothpick until it is
      found or expelled. 

PMID- 25589541
TI  - Effect of Delay to Definitive Surgical Fixation on Wound Complications in the
      Treatment of Closed, Intra-articular Calcaneus Fractures.
AB  - BACKGROUND: There are conflicting data regarding the benefits of delaying
      operative fixation of calcaneus fractures to decrease wound complication rates.
      The purpose of this study was to examine the effect of delaying fixation on wound
      complication rates as well as to identify other risk factors. METHODS: A
      retrospective review at 4 institutions, including 24 surgeons, identified 405
      closed, operatively treated, intra-articular calcaneus fractures. We compared
      fractures with and without wound complications with regards to patient
      demographics, medical risk factors, fracture severity, time to fixation,
      operative approach, primary subtalar arthrodesis, and surgeon experience.
      RESULTS: Wound complications were observed in 21% (87/405) of fractures, of which
      33% (29/87) required operative intervention. Male sex (P = .032), smoking (P =
      .028), and the extensile lateral approach (P < .001) were associated with higher
      complication rates. Fractures treated with an extensile lateral approach had an
      overall wound complication rate of 32.1%, while those treated with a sinus tarsi
      or percutaneous approach had an overall wound complication rate of 8.3% (odds
      ratio [OR], 5.3; 95% confidence interval [CI], 2.9-9.5; P < .001). Among patients
      treated with an extensile lateral approach, delayed operative fixation did not
      decrease wound complication rates despite comparable fracture severity across
      time points. In contrast, among fractures treated with less invasive approaches,
      delayed fixation beyond 2 weeks resulted in a significantly increased wound
      complication rate of 15.2% as compared to a wound complication rate of only 2.1%
      among fractures treated within a week of injury (OR, 3.2; 95% CI, 1.3-9.5; P =
      .01). This was observed despite similar fracture severity across time points.
      Primary subtalar arthrodesis did not impact complication rates. A higher wound
      complication rate among senior surgeons was likely secondary to their
      predilection for the extensile lateral approach. CONCLUSION: Delaying definitive
      fixation of closed, intra-articular calcaneus fractures did not decrease wound
      complication rates when using the extensile lateral approach, and we found an
      increased wound complication rate when using less invasive approaches. LEVEL OF
      EVIDENCE: Level III, observational study.

PMID- 25589542
TI  - Correlation of postoperative midfoot position with outcome following
      reconstruction of the stage II adult acquired flatfoot deformity.
AB  - BACKGROUND: No studies investigating the effect of the midfoot (talonavicular
      joint) position on clinical outcomes following flatfoot reconstruction have been
      performed. The purpose of our study was to determine whether a postoperative
      abducted or adducted forefoot alignment, as determined from anteroposterior (AP)
      radiographs, was associated with a difference in outcomes using the Foot and
      Ankle Outcome Score (FAOS). METHODS: Midfoot abduction was defined on
      postoperative AP radiographs, evaluated at a mean of 1.9 years in 55 patients
      from the authors' institution who underwent flatfoot reconstruction for a stage
      II adult acquired flatfoot deformity (AAFD), as a lateral incongruency angle
      greater than 5 degrees, a talonavicular uncoverage angle greater than 8 degrees,
      and a talo-first metatarsal angle greater than 8 degrees based on previously
      reported measurements. Patients with 2 or more measurements in the abduction
      category were classified as the abduction group (n = 30); those with 1 or fewer
      measurements in the abduction category were placed in the adduction group (n =
      25). The preoperative and postoperative FAOS values with a mean follow-up of 3.1
      years were compared using Wilcoxon rank-sum tests. RESULTS: Patients corrected to
      a position of adduction showed significantly lower improvement in the FAOS daily
      activities (P = .012) and quality of life subscales (P = .046). The mean
      improvement in subscale scores for the adducted group was lower for pain (P =
      .052) and sports activities (P = .085) but did not reach statistical
      significance. No significant difference in the FAOS symptoms subscale (P = .372)
      between groups was found. CONCLUSION: Correction of the talonavicular joint to a
      position of adduction following a stage II AAFD was associated with decreased
      patient outcomes in daily activities and quality of life compared with an
      abducted position. These results suggest that overcorrection to a position of
      midfoot adduction leads to a lesser amount of individual patient improvement in
      reconstruction of a stage II AAFD.

PMID- 25589543
TI  - DNA lesion identity drives choice of damage tolerance  pathway in murine cell
      chromosomes.
AB  - DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology
      dependent repair (HDR) functions to bypass DNA lesions encountered during
      replication, and is critical for maintaining genome stability. Here, we present
      piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA
      containing a known lesion, measures the division of labor between the two DDT
      pathways. We show that in the absence of DNA damage response, tolerance of the
      most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse
      embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is
      bypassed primarily by HDR, providing the first evidence for this mechanism being
      the main tolerance pathway for a biologically important lesion in a mammalian
      genome. We also show that, far from being a last-resort strategy as it is
      sometimes portrayed, TLS operates alongside nucleotide excision repair, handling
      40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic
      stem cells, exhibiting the same pattern-mutagenic TLS included-despite the risk
      of propagating mutations along all cell lineages. The new method highlights the
      importance of HDR, and provides an effective tool for studying DDT in mammalian
      cells.

PMID- 25589544
TI  - Opposing roles of H3- and H4-acetylation in the  regulation of nucleosome
      structure--a FRET study.
AB  - Using FRET in bulk and on single molecules, we assessed the structural role of
      histone acetylation in nucleosomes reconstituted on the 170 bp long Widom 601
      sequence. We followed salt-induced nucleosome disassembly, using donor-acceptor
      pairs on the ends or in the internal part of the nucleosomal DNA, and on H2B
      histone for measuring H2A/H2B dimer exchange. This allowed us to distinguish the
      influence of acetylation on salt-induced DNA unwrapping at the entry-exit site
      from its effect on nucleosome core dissociation. The effect of lysine acetylation
      is not simply cumulative, but showed distinct histone-specificity. Both H3- and
      H4-acetylation enhance DNA unwrapping above physiological ionic strength;
      however, while H3-acetylation renders the nucleosome core more sensitive to salt
      induced dissociation and to dimer exchange, H4-acetylation counteracts these
      effects. Thus, our data suggest, that H3- and H4-acetylation have partially
      opposing roles in regulating nucleosome architecture and that distinct aspects of
      nucleosome dynamics might be independently controlled by individual histones.

PMID- 25589545
TI  - Amplification of small molecule-inducible gene  expression via tuning of
      intracellular receptor  densities.
AB  - Ligand-responsive transcription factors in prokaryotes found simple small
      molecule-inducible gene expression systems. These have been extensively used for
      regulated protein production and associated biosynthesis of fine chemicals.
      However, the promoter and protein engineering approaches traditionally used often
      pose significant restrictions to predictably and rapidly tune the expression
      profiles of inducible expression systems. Here, we present a new unified and
      rational tuning method to amplify the sensitivity and dynamic ranges of versatile
      small molecule-inducible expression systems. We employ a systematic variation of
      the concentration of intracellular receptors for transcriptional control. We show
      that a low density of the repressor receptor (e.g. TetR and ArsR) in the cell can
      significantly increase the sensitivity and dynamic range, whereas a high
      activator receptor (e.g. LuxR) density achieves the same outcome. The
      intracellular concentration of receptors can be tuned in both discrete and
      continuous modes by adjusting the strength of their cognate driving promoters. We
      exemplified this approach in several synthetic receptor-mediated sensing
      circuits, including a tunable cell-based arsenic sensor. The approach offers a
      new paradigm to predictably tune and amplify ligand-responsive gene expression
      with potential applications in synthetic biology and industrial biotechnology.

PMID- 25589546
TI  - Interaction between the RNA-dependent ATPase and  poly(A) polymerase subunits of
      the TRAMP complex  is mediated by short peptides and important for  snoRNA
      processing.
AB  - The RNA exosome is one of the main 3' to 5' exoribonucleases in eukaryotic cells.
      Although it is responsible for degradation or processing of a wide variety of
      substrate RNAs, it is very specific and distinguishes between substrate and non
      substrate RNAs as well as between substrates that need to be 3' processed and
      those that need to be completely degraded. This specificity does not appear to be
      determined by the exosome itself but rather by about a dozen other proteins. Four
      of these exosome cofactors have enzymatic activity, namely, the nuclear RNA
      dependent ATPase Mtr4, its cytoplasmic paralog Ski2 and the nuclear non-canonical
      poly(A) polymerases, Trf4 and Trf5. Mtr4 and either Trf4 or Trf5 assemble into a
      TRAMP complex. However, how these enzymes assemble into a TRAMP complex and the
      functional consequences of TRAMP complex assembly remain unknown. Here, we
      identify an important interaction site between Mtr4 and Trf5, and show that
      disrupting the Mtr4/Trf interaction disrupts specific TRAMP and exosome
      functions, including snoRNA processing.

PMID- 25589548
TI  - Advanced digital subtraction angiography and MR fusion imaging protocol applied
      to accurate placement of flow diverter device.
AB  - In recent years there has been a progressive increase in interventional
      neuroradiology procedures, partially due to improvements in devices, but also to
      the simultaneous development of technologies and radiological images. Cone beam
      CT (Dyna-CT; Siemens) is a method recently used to obtain pseudo CT images from
      digital subtraction angiography (DSA) with a flat panel detector. Using dedicated
      software, it is then possible to merge Dyna-CT images with images from a
      different source. We report here the usefulness of advanced DSA techniques (Syngo
      Dyna CT, three-dimensional DSA iPilot) for the treatment of an intracranial
      aneurysm with a flow diverter device. Merging MR and Dyna-CT images at the end of
      the procedure proved to be a simple and rapid additional method of verifying the
      success of the intervention. 

PMID- 25589547
TI  - Sequences spanning the leader-repeat junction  mediate CRISPR adaptation to phage
      in  Streptococcus thermophilus.
AB  - CRISPR-Cas systems are RNA-based immune systems that protect prokaryotes from
      invaders such as phages and plasmids. In adaptation, the initial phase of the
      immune response, short foreign DNA fragments are captured and integrated into
      host CRISPR loci to provide heritable defense against encountered foreign nucleic
      acids. Each CRISPR contains a ~100-500 bp leader element that typically includes
      a transcription promoter, followed by an array of captured ~35 bp sequences
      (spacers) sandwiched between copies of an identical ~35 bp direct repeat
      sequence. New spacers are added immediately downstream of the leader. Here, we
      have analyzed adaptation to phage infection in Streptococcus thermophilus at the
      CRISPR1 locus to identify cis-acting elements essential for the process. We show
      that the leader and a single repeat of the CRISPR locus are sufficient for
      adaptation in this system. Moreover, we identified a leader sequence element
      capable of stimulating adaptation at a dormant repeat. We found that sequences
      within 10 bp of the site of integration, in both the leader and repeat of the
      CRISPR, are required for the process. Our results indicate that information at
      the CRISPR leader-repeat junction is critical for adaptation in this Type II-A
      system and likely other CRISPR-Cas systems.

PMID- 25589550
TI  - Genetic, biochemical, and serological characterization of a new pneumococcal
      serotype, 6H, and generation of a pneumococcal strain producing three different
      capsular repeat units.
AB  - Streptococcus pneumoniae clinical isolates were recently described that produced
      capsular polysaccharide with properties of both serotypes 6A and 6B. Their hybrid
      serological property correlated with mutations affecting the glycosyltransferase
      WciP, which links rhamnose to ribitol by an alpha(1-3) linkage for serotypes 6A
      and 6C and an alpha(1-4) linkage for serotypes 6B and 6D. The isolates had
      mutations in the triad residues of WciP that have been correlated with enzyme
      specificity. The canonical triad residues of WciP are Ala192-Ser195-Arg254 for
      serotypes 6A and 6C and Ser192-Asn195-Gly254 for serotypes 6B and 6D. To prove
      that the mutations in the triad residues are responsible for the hybrid serotype,
      we introduced the previously described Ala192-Cys195-Arg254 triad into a 6A
      strain and found that the change made WciP bispecific, resulting in 6A and 6B
      repeat unit expression, although 6B repeat unit production was favored over
      production of 6A repeat units. Likewise, this triad permitted a 6C strain to
      express 6C and 6D repeat units. With reported bispecificity in WciN, which adds
      either glucose or galactose as the second sugar in the serogroup 6 repeat unit,
      the possibility exists for a strain to simultaneously produce all four serogroup
      6 repeat units; however, when genes encoding both bispecific enzymes were
      introduced into a 6A strain, only 6A, 6B, and 6D repeat units were detected
      serologically. Nonetheless, this may be the first example of a bacterial
      polysaccharide with three different repeat units. This strategy of expressing
      multiple repeat units in a single polymer is a novel approach to broadening
      vaccine coverage by eliminating the need for multiple polysaccharide sources to
      cover multiple serogroup members. 

PMID- 25589549
TI  - Quest for correlates of protection against tuberculosis.
AB  - A major impediment to tuberculosis (TB) vaccine development is the lack of
      reliable correlates of immune protection or biomarkers that would predict vaccine
      efficacy. Gamma interferon (IFN-gamma) produced by CD4(+) T cells and, recently,
      multifunctional CD4(+) T cells secreting IFN-gamma, tumor necrosis factor (TNF),
      and interleukin-2 (IL-2) have been used in vaccine studies as a measurable immune
      parameter, reflecting activity of a vaccine and potentially predicting
      protection. However, accumulating experimental evidence suggests that host
      resistance against Mycobacterium tuberculosis infection is independent of IFN
      gamma and TNF secretion from CD4(+) T cells. Furthermore, the booster vaccine
      MVA85A, despite generating a high level of multifunctional CD4(+) T cell response
      in the host, failed to confer enhanced protection in vaccinated subjects. These
      findings suggest the need for identifying reliable correlates of protection to
      determine the efficacy of TB vaccine candidates. This article focuses on
      alternative pathways that mediate M. tuberculosis control and their potential for
      serving as markers of protection. The review also discusses the significance of
      investigating the natural human immune response to M. tuberculosis to identify
      the correlates of protection in vaccination. 

PMID- 25589551
TI  - Mapping antigenic motifs in the trypomastigote small surface antigen from
      Trypanosoma cruzi.
AB  - The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from
      Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino
      acid polymorphisms in parasite isolates. TSSA expression is restricted to the
      surface of infective cell-derived trypomastigotes, where it functions as an
      adhesin and engages surface receptors on the host cell as a prerequisite for
      parasite internalization. Previous results have established TSSA-CL, the isoform
      encoded by the CL Brener clone, as an appealing candidate for use in serology
      based diagnostics for Chagas disease. Here, we used a combination of peptide- and
      recombinant protein-based tools to map the antigenic structure of TSSA-CL at
      maximal resolution. Our results indicate the presence of different partially
      overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which
      contains most of the polymorphisms found in parasite isolates. Based on these
      results, we assessed the serodiagnostic performance of a 21-amino-acid-long
      peptide that spans TSSA-CL major antigenic determinants, which was similar to the
      performance of the previously validated glutathione S-transferase (GST)-TSSA-CL
      fusion molecule. Furthermore, the tools developed for the antigenic
      characterization of the TSSA antigen were also used to explore other potential
      diagnostic applications of the anti-TSSA humoral response in Chagasic patients.
      Overall, our present results provide additional insights into the antigenic
      structure of TSSA-CL and support this molecule as an excellent target for
      molecular intervention in Chagas disease. 

PMID- 25589552
TI  - Long-term immunogenicity of an inactivated split-virion 2009 pandemic influenza A
      H1N1 virus vaccine with or without aluminum adjuvant in mice.
AB  - In 2009, a global epidemic of influenza A(H1N1) virus caused the death of tens of
      thousands of people. Vaccination is the most effective means of controlling an
      epidemic of influenza and reducing the mortality rate. In this study, the long
      term immunogenicity of influenza A/California/7/2009 (H1N1) split vaccine was
      observed as long as 15 months (450 days) after immunization in a mouse model.
      Female BALB/c mice were immunized intraperitoneally with different doses of
      aluminum-adjuvanted vaccine. The mice were challenged with a lethal dose (10* 50%
      lethal dose [LD(50)]) of homologous virus 450 days after immunization. The
      results showed that the supplemented aluminum adjuvant not only effectively
      enhanced the protective effect of the vaccine but also reduced the immunizing
      dose of the vaccine. In addition, the aluminum adjuvant enhanced the IgG antibody
      level of mice immunized with the H1N1 split vaccine. The IgG level was correlated
      to the survival rate of the mice. Aluminum-adjuvanted inactivated split-virion
      2009 pandemic influenza A H1N1 vaccine has good immunogenicity and provided long
      term protection against lethal influenza virus challenge in mice.

PMID- 25589553
TI  - Antibody-mediated complement C3b/iC3b binding to group B Streptococcus in paired
      mother and baby serum samples in a refugee population on the Thailand-Myanmar
      border.
AB  - Streptococcus agalactiae (group B streptococcus [GBS]) is the leading cause of
      neonatal sepsis and meningitis. In this study, we determined antibody-mediated
      deposition of complement C3b/iC3b onto the bacterial cell surface of GBS
      serotypes Ia, Ib, II, III, and V. This was determined for 520 mother and
      umbilical cord serum sample pairs obtained at the time of birth from a population
      on the Thailand-Myanmar border. Antibody-mediated deposition of complement
      C3b/iC3b was detected to at least one serotype in 91% of mothers, despite a known
      carriage rate in this population of only 12%. Antibody-mediated C3b/iC3b
      deposition corresponded to known carriage rates, with the highest levels of
      complement deposition observed onto the most prevalent serotype (serotype II)
      followed by serotypes Ia, III, V, and Ib. Finally, neonates born to mothers
      carrying serotype II GBS at the time of birth showed higher antibody-mediated
      C3b/iC3b deposition against serotype II GBS than neonates born to mothers with no
      serotype II carriage. Assessment of antibody-mediated C3b/iC3b deposition against
      GBS may provide insights into the seroepidemiology of anti-GBS antibodies in
      mothers and infants in different populations. 

PMID- 25589554
TI  - Next-generation sequencing reveals a controlled immune response to Zaire Ebola
      virus challenge in cynomolgus macaques immunized with vesicular stomatitis virus
      expressing Zaire Ebola virus glycoprotein (VSVDeltaG/EBOVgp).
AB  - Vesicular stomatitis virus expressing Zaire Ebola virus (EBOV) glycoprotein
      (VSVDeltaG/EBOVgp) could be used as a vaccine to meet the 2014 Ebola virus
      outbreak. To characterize the host response to this vaccine, we used mRNA
      sequencing to analyze peripheral blood mononuclear cells (PBMCs) from cynomolgus
      macaques after VSVDeltaG/EBOVgp immunization and subsequent EBOV challenge. We
      found a controlled transcriptional response that transitioned to immune
      regulation as the EBOV was cleared. This observation supports the safety of the
      vaccine. 

PMID- 25589555
TI  - Evaluation of a multiplex bead immunoassay for determination of immune status to
      varicella-zoster virus in medical center students and employees.
AB  - This study evaluated an enzyme immunoassay, a multiplex bead immunoassay (MBIA),
      and the anticomplement immunofluorescence (ACIF) test for detecting varicella
      zoster virus IgG antibodies in sera from medical center students and employees.
      The agreement between methods was >=95%. The MBIA was less sensitive than was the
      ACIF test, with a negative predictive value of 66.7%. 

PMID- 25589556
TI  - HDL particle size is a critical determinant of ABCA1-mediated macrophage cellular
      cholesterol export.
AB  - RATIONALE: High-density lipoprotein (HDL) is a heterogeneous population of
      particles. Differences in the capacities of HDL subfractions to remove cellular
      cholesterol may explain variable correlations between HDL-cholesterol and
      cardiovascular risk and inform future targets for HDL-related therapies. The ATP
      binding cassette transporter A1 (ABCA1) facilitates cholesterol efflux to lipid
      free apolipoprotein A-I, but the majority of apolipoprotein A-I in the
      circulation is transported in a lipidated state and ABCA1-dependent efflux to
      individual HDL subfractions has not been systematically studied. OBJECTIVE: Our
      aims were to determine which HDL particle subfractions are most efficient in
      mediating cellular cholesterol efflux from foam cell macrophages and to identify
      the cellular cholesterol transporters involved in this process. METHODS AND
      RESULTS: We used reconstituted HDL particles of defined size and composition,
      isolated subfractions of human plasma HDL, cell lines stably expressing ABCA1 or
      ABCG1, and both mouse and human macrophages in which ABCA1 or ABCG1 expression
      was deleted. We show that ABCA1 is the major mediator of macrophage cholesterol
      efflux to HDL, demonstrating most marked efficiency with small, dense HDL
      subfractions (HDL3b and HDL3c). ABCG1 has a lesser role in cholesterol efflux and
      a negligible role in efflux to HDL3b and HDL3c subfractions. CONCLUSIONS: Small,
      dense HDL subfractions are the most efficient mediators of cholesterol efflux,
      and ABCA1 mediates cholesterol efflux to small dense HDL and to lipid-free
      apolipoprotein A-I. HDL-directed therapies should target increasing the
      concentrations or the cholesterol efflux capacity of small, dense HDL species in
      vivo.

PMID- 25589558
TI  - Parsing the role of NADPH oxidase enzymes and reactive oxygen species in heart
      failure.

PMID- 25589559
TI  - Normal saline flushes performed once daily maintain peripheral intravenous
      catheter patency: a randomised controlled trial.
AB  - OBJECTIVE: Recent evidence supports the use of normal saline flushes in place of
      heparin to maintain the patency of peripheral intravenous locks (IVLs); however,
      there are no data regarding the recommended flush frequency. STUDY DESIGN: This
      was an open, non-inferiority, randomised controlled trial. Children with IVLs,
      aged 1-17 years, were randomly assigned to receive saline flushing every 12 h
      (group A) or every 24 h (group B). The main outcome was the maintenance of
      catheter patency. RESULTS: Four hundred patients were randomised; 198 subjects
      were analysed in the 12 h group and 199 in the 24 h group (three patients were
      lost at follow-up). Occlusion occurred in 15 children (7.6%) in group A versus 9
      (4.5%) in group B (p=0.21). The difference in catheter patency was +3.1% in
      favour of the 24 h group (95% CI -1.6% to 7.7%), showing the non-inferiority of
      the 24 h procedure (the non-inferiority margin was set at -4%). Catheter-related
      complications were not different between the two groups (12.1% in group A vs 9.5%
      in group B; p=0.42). CONCLUSIONS: A flushing procedure with one flush per day
      allows maintenance of catheter patency without an increase in catheter-related
      complications. We propose a simplification of the flushing procedure with only
      one flush per day, thereby reducing costs (materials use and nursing time),
      labour and unnecessary manipulation of the catheters which can cause distress in
      younger children and their parents. TRIAL REGISTRATION NUMBER: The study is
      registered in the international database ClinicalTrial.gov under registration
      number NCT02221024.

PMID- 25589557
TI  - NADPH oxidase 4 induces cardiac fibrosis and hypertrophy through activating
      Akt/mTOR and NFkappaB signaling pathways.
AB  - BACKGROUND: NADPH oxidase 4 (Nox4) has been implicated in cardiac remodeling, but
      its precise role in cardiac injury remains controversial. Furthermore, little is
      known about the downstream effector signaling pathways activated by Nox4-derived
      reactive oxygen species in the myocardium. We investigated the role of Nox4 and
      Nox4-associated signaling pathways in the development of cardiac remodeling.
      METHODS AND RESULTS: Cardiac-specific human Nox4 transgenic mice (c-hNox4Tg) were
      generated. Four groups of mice were studied: (1) control mice, littermates that
      are negative for hNox4 transgene but Cre positive; (2) c-hNox4 Tg mice; (3)
      angiotensin II (AngII)-infused control mice; and (4) c-hNox4Tg mice infused with
      AngII. The c-hNox4Tg mice exhibited an ~10-fold increase in Nox4 protein
      expression and an 8-fold increase in the production of reactive oxygen species,
      and manifested cardiac interstitial fibrosis. AngII infusion to control mice
      increased cardiac Nox4 expression and induced fibrosis and hypertrophy. The Tg
      mice receiving AngII exhibited more advanced cardiac remodeling and robust
      elevation in Nox4 expression, indicating that AngII worsens cardiac injury, at
      least in part by enhancing Nox4 expression. Moreover, hNox4 transgene and AngII
      infusion induced the expression of cardiac fetal genes and activated the Akt-mTOR
      and NFkappaB signaling pathways. Treatment of AngII-infused c-hNox4Tg mice with
      GKT137831, a Nox4/Nox1 inhibitor, abolished the increase in oxidative stress,
      suppressed the Akt-mTOR and NFkappaB signaling pathways, and attenuated cardiac
      remodeling. CONCLUSIONS: Upregulation of Nox4 in the myocardium causes cardiac
      remodeling through activating Akt-mTOR and NFkappaB signaling pathways.
      Inhibition of Nox4 has therapeutic potential to treat cardiac remodeling.

PMID- 25589560
TI  - Behaviour and development in 24-month-old moderately preterm toddlers.
AB  - OBJECTIVE: Moderately preterm children (gestational age 32-36+6 weeks) are at
      risk of cognitive and behaviour problems at school age. The aim of this study was
      to investigate if these problems are already present at the age of 2 years. STUDY
      DESIGN: Developmental outcome was assessed at 24-months (corrected age) with the
      Bayley-III-NL in 116 moderately preterm (M=34.66 +/- 1.35 weeks gestation) and 99
      term born children (M=39.45 +/- 0.98 weeks gestation). Behaviour problems were
      assessed with the Child Behaviour Checklist. RESULTS: With age corrected for
      prematurity, moderately preterm children scored below term peers on Receptive
      Communication skills (11.05 +/- 2.58 vs 12.02 +/- 2.74, p=0.02). Without
      correcting age for prematurity, moderately preterm children scored below term
      born peers on Cognition (8.97 +/- 2.11 vs 10.68 +/- 2.35, p<0.001), Fine Motor
      (10.33 +/- 2.15 vs 11.96 +/- 2.15, p<0.001), Gross Motor (8.47 +/- 2.55 vs 9.39+/
      2.80, p=0.05), Receptive Communication (10.09 +/- 2.48 vs 12.02 +/- 2.74,
      p<0.001) and Expressive Communication (10.33 +/- 2.43 vs 11.49 +/- 2.51, p=0.005)
      skills. Compared with term peers, more moderately preterm children showed a
      (mild) delay (ie, scaled score <7) in gross motor skills with age uncorrected for
      prematurity (20.7% vs 11.2%, p=0.04). Moderately preterm children had more
      internalising behaviour problems than term children (44.76 +/- 8.94 vs 41.54 +/-
      8.56, p=0.03). No group differences were found in percentages of (sub)clinical
      scores. CONCLUSIONS: At the age of 2 years, uncorrected for prematurity,
      differences in cognition, communication, and motor development were present in
      moderately preterm children compared with term born peers. After correcting age
      for prematurity, a difference was only found for receptive communication skills.
      In addition, moderately preterm children show more internalising behaviour
      problems.

PMID- 25589561
TI  - Patterns of bruising in preschool children--a longitudinal study.
AB  - INTRODUCTION: This study aims to identify the prevalence and pattern of bruises
      in preschool children over time, and explore influential variables METHODS:
      Prospective longitudinal study of children (<6 years) where bruises were recorded
      on a body chart, weekly for up to 12 weeks. The number and location of bruises
      were analysed according to development. Longitudinal analysis was performed using
      multilevel modelling. RESULTS: 3523 bruises recorded from 2570 data collections
      from 328 children (mean age 19 months); 6.7% of 1010 collections from premobile
      children had at least one bruise (2.2% of babies who could not roll over and 9.8%
      in those who could), compared with 45.6% of 478 early mobile and 78.8% of 1082
      walking child collections. The most common site affected in all groups was below
      the knees, followed by 'facial T' and head in premobile and early mobile. The
      ears, neck, buttocks, genitalia and hands were rarely bruised (<1% of all
      collections). None of gender, season or the level of social deprivation
      significantly influenced bruising patterns, although having a sibling increased
      the mean number of bruises. There was considerable variation in the number of
      bruises recorded between different children which increased with developmental
      stage and was greater than the variation between numbers of bruises in
      collections from the same child over time. CONCLUSIONS: These data should help
      clinicians understand the patterns of 'everyday bruising' and recognise children
      who have an unusual numbers or distribution of bruises who may need assessment
      for physical abuse or bleeding disorders.

PMID- 25589562
TI  - Child mortality in the developed world: the UK and the rest.

PMID- 25589565
TI  - In vivo recording of aerodynamic force with an aerodynamic force platform: from
      drones to birds.
AB  - Flapping wings enable flying animals and biomimetic robots to generate elevated
      aerodynamic forces. Measurements that demonstrate this capability are based on
      experiments with tethered robots and animals, and indirect force calculations
      based on measured kinematics or airflow during free flight. Remarkably, there
      exists no method to measure these forces directly during free flight. Such in
      vivo recordings in freely behaving animals are essential to better understand the
      precise aerodynamic function of their flapping wings, in particular during the
      downstroke versus upstroke. Here, we demonstrate a new aerodynamic force platform
      (AFP) for non-intrusive aerodynamic force measurement in freely flying animals
      and robots. The platform encloses the animal or object that generates fluid force
      with a physical control surface, which mechanically integrates the net
      aerodynamic force that is transferred to the earth. Using a straightforward
      analytical solution of the Navier-Stokes equation, we verified that the method is
      accurate. We subsequently validated the method with a quadcopter that is
      suspended in the AFP and generates unsteady thrust profiles. These independent
      measurements confirm that the AFP is indeed accurate. We demonstrate the
      effectiveness of the AFP by studying aerodynamic weight support of a freely
      flying bird in vivo. These measurements confirm earlier findings based on
      kinematics and flow measurements, which suggest that the avian downstroke, not
      the upstroke, is primarily responsible for body weight support during take-off
      and landing. 

PMID- 25589566
TI  - Constructor theory of life.
AB  - Neo-Darwinian evolutionary theory explains how the appearance of purposive design
      in the adaptations of living organisms can have come about without their
      intentionally being designed. The explanation relies crucially on the possibility
      of certain physical processes: mainly, gene replication and natural selection. In
      this paper, I show that for those processes to be possible without the design of
      biological adaptations being encoded in the laws of physics, those laws must have
      certain other properties. The theory of what these properties are is not part of
      evolution theory proper, yet without it the neo-Darwinian theory does not fully
      achieve its purpose of explaining the appearance of design. To this end, I apply
      constructor theory's new mode of explanation to express exactly within physics
      the appearance of design, no-design laws, and the logic of self-reproduction and
      natural selection. I conclude that self-reproduction, replication and natural
      selection are possible under no-design laws, the only non-trivial condition being
      that they allow digital information to be physically instantiated. This has an
      exact characterization in the constructor theory of information. I also show that
      under no-design laws an accurate replicator requires the existence of a 'vehicle'
      constituting, together with the replicator, a self-reproducer. 

PMID- 25589564
TI  - Many hepatitis C reinfections that spontaneously clear may be undetected: Markov
      chain Monte Carlo analysis of observational study data.
AB  - Hepatitis C virus (HCV) reinfection rates are probably underestimated due to
      reinfection episodes occurring between study visits. A Markov model of HCV
      reinfection and spontaneous clearance was fitted to empirical data. Bayesian post
      estimation was used to project reinfection rates, reinfection spontaneous
      clearance probability and duration of reinfection. Uniform prior probability
      distributions were assumed for reinfection rate (more than 0), spontaneous
      clearance probability (0-1) and duration (0.25-6.00 months). Model estimates were
      104 per 100 person-years (95% CrI: 21-344), 0.84 (95% CrI: 0.59-0.98) and 1.3
      months (95% CrI: 0.3-4.1) for reinfection rate, spontaneous clearance probability
      and duration, respectively. Simulation studies were used to assess model
      validity, demonstrating that the Bayesian model estimates provided useful
      information about the possible sources and magnitude of bias in epidemiological
      estimates of reinfection rates, probability of reinfection clearance and duration
      or reinfection. The quality of the Bayesian estimates improved for larger samples
      and shorter test intervals. Uncertainty in model estimates notwithstanding,
      findings suggest that HCV reinfections frequently and quickly result in
      spontaneous clearance, with many reinfection events going unobserved. 

PMID- 25589563
TI  - Investigating cell mechanics with atomic force microscopy.
AB  - Transmission of mechanical force is crucial for normal cell development and
      functioning. However, the process of mechanotransduction cannot be studied in
      isolation from cell mechanics. Thus, in order to understand how cells 'feel', we
      must first understand how they deform and recover from physical perturbations.
      Owing to its versatility, atomic force microscopy (AFM) has become a popular tool
      to study intrinsic cellular mechanical properties. Used to directly manipulate
      and examine whole and subcellular reactions, AFM allows for top-down and
      reconstitutive approaches to mechanical characterization. These studies show that
      the responses of cells and their components are complex, and largely depend on
      the magnitude and time scale of loading. In this review, we generally describe
      the mechanotransductive process through discussion of well-known mechanosensors.
      We then focus on discussion of recent examples where AFM is used to specifically
      probe the elastic and inelastic responses of single cells undergoing deformation.
      We present a brief overview of classical and current models often used to
      characterize observed cellular phenomena in response to force. Both simple
      mechanistic models and complex nonlinear models have been used to describe the
      observed cellular behaviours, however a unifying description of cell mechanics
      has not yet been resolved. 

PMID- 25589567
TI  - Demographic buffering: titrating the effects of birth rate and imperfect immunity
      on epidemic dynamics.
AB  - Host demography can alter the dynamics of infectious disease. In the case of
      perfectly immunizing infections, observations of strong sensitivity to
      demographic variation have been mechanistically explained through analysis of the
      susceptible-infected-recovered (SIR) model that assumes lifelong immunity
      following recovery from infection. When imperfect immunity is incorporated into
      this framework via the susceptible-infected-recovered-susceptible (SIRS) model,
      with individuals regaining full susceptibility following recovery, we show that
      rapid loss of immunity is predicted to buffer populations against the effects of
      demographic change. However, this buffering is contrary to the dependence on
      demography recently observed for partially immunizing infections such as
      rotavirus and respiratory syncytial virus. We show that this discrepancy arises
      from a key simplification embedded in the SIR(S) framework, namely that the
      potential for differential immune responses to repeat exposures is ignored. We
      explore the minimum additional immunological information that must be included to
      reflect the range of observed dependencies on demography. We show that including
      partial protection and lower transmission following primary infection is
      sufficient to capture more realistic reduced levels of buffering, in addition to
      changes in epidemic timing, across a range of partially and fully immunizing
      infections. Furthermore, our results identify key variables in this relationship,
      including R0. 

PMID- 25589568
TI  - Creating the brain and interacting with the brain: an integrated approach to
      understanding the brain.
AB  - In the past two decades, brain science and robotics have made gigantic advances
      in their own fields, and their interactions have generated several
      interdisciplinary research fields. First, in the 'understanding the brain by
      creating the brain' approach, computational neuroscience models have been applied
      to many robotics problems. Second, such brain-motivated fields as cognitive
      robotics and developmental robotics have emerged as interdisciplinary areas among
      robotics, neuroscience and cognitive science with special emphasis on humanoid
      robots. Third, in brain-machine interface research, a brain and a robot are
      mutually connected within a closed loop. In this paper, we review the theoretical
      backgrounds of these three interdisciplinary fields and their recent progress.
      Then, we introduce recent efforts to reintegrate these research fields into a
      coherent perspective and propose a new direction that integrates brain science
      and robotics where the decoding of information from the brain, robot control
      based on the decoded information and multimodal feedback to the brain from the
      robot are carried out in real time and in a closed loop. 

PMID- 25589569
TI  - Stick-slip friction of gecko-mimetic flaps on smooth and rough surfaces.
AB  - The discovery and understanding of gecko 'frictional-adhesion' adhering and
      climbing mechanism has allowed researchers to mimic and create gecko-inspired
      adhesives. A few experimental and theoretical approaches have been taken to
      understand the effect of surface roughness on synthetic adhesive performance, and
      the implications of stick-slip friction during shearing. This work extends
      previous studies by using a modified surface forces apparatus to quantitatively
      measure and model frictional forces between arrays of polydimethylsiloxane gecko
      footpad-mimetic tilted microflaps against smooth and rough glass surfaces.
      Constant attachments and detachments occur between the surfaces during shearing,
      as described by an avalanche model. These detachments ultimately result in
      failure of the adhesion interface and have been characterized in this study.
      Stick-slip friction disappears with increasing velocity when the flaps are
      sheared against a smooth silica surface; however, stick-slip was always present
      at all velocities and loads tested when shearing the flaps against rough glass
      surfaces. These results demonstrate the significance of pre-load, shearing
      velocity, shearing distances, commensurability and shearing direction of gecko
      mimetic adhesives and provide us a simple model for analysing and/or designing
      such systems. 

PMID- 25589570
TI  - Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase
      and RhoA kinase sensors.
AB  - The study of mesenchymal stem cell (MSC) migration under flow conditions with
      investigation of the underlying molecular mechanism could lead to a better
      understanding and outcome in stem-cell-based cell therapy and regenerative
      medicine. We used peer-reviewed open source software to develop methods for
      efficiently and accurately tracking, measuring and processing cell migration as
      well as morphology. Using these tools, we investigated MSC migration under flow
      induced shear and tested the molecular mechanism with stable knockdown of focal
      adhesion kinase (FAK) and RhoA kinase (ROCK). Under steady flow, MSCs migrated
      following the flow direction in a shear stress magnitude-dependent manner, as
      assessed by root mean square displacement and mean square displacement, motility
      coefficient and confinement ratio. Silencing FAK in MSCs suppressed morphology
      adaptation capability and reduced cellular motility for both static and flow
      conditions. Interestingly, ROCK silencing significantly increased migration
      tendency especially under flow. Blocking ROCK, which is known to reduce
      cytoskeletal tension, may lower the resistance to skeletal remodelling during the
      flow-induced migration. Our data thus propose a potentially differential role of
      focal adhesion and cytoskeletal tension signalling elements in MSC migration
      under flow shear. 

PMID- 25589571
TI  - C60 fullerene promotes lung monolayer collapse.
AB  - Airborne nanometre-sized pollutants are responsible for various respiratory
      diseases. Such pollutants can reach the gas-exchange surface in the alveoli,
      which is lined with a monolayer of lung surfactant. The relationship between
      physiological effects of pollutants and molecular-level interactions is largely
      unknown. Here, we determine the effects of carbon nanoparticles on the properties
      of a model of lung monolayer using molecular simulations. We simulate phase
      separated lipid monolayers in the presence of a model pollutant nanoparticle, C60
      fullerene. In the absence of nanoparticles, the monolayers collapse only at very
      low surface tensions (around 0 mN m(-1)). In the presence of nanoparticles,
      instead, monolayer collapse is observed at significantly higher surface tensions
      (up to ca 10 mN m(-1)). Collapse at higher tensions is related to lower
      mechanical rigidity of the monolayer. It is possible that similar mechanisms
      operate on lung surfactant in vivo, which suggests that health effects of
      airborne carbon nanoparticles may be mediated by alterations of the mechanical
      properties of lung surfactant.

PMID- 25589572
TI  - Automated segmentation of the lamina cribrosa using Frangi's filter: a novel
      approach for rapid identification of tissue volume fraction and beam orientation
      in a trabeculated structure in the eye.
AB  - The lamina cribrosa (LC) is a tissue in the posterior eye with a complex
      trabecular microstructure. This tissue is of great research interest, as it is
      likely the initial site of retinal ganglion cell axonal damage in glaucoma.
      Unfortunately, the LC is difficult to access experimentally, and thus imaging
      techniques in tandem with image processing have emerged as powerful tools to
      study the microstructure and biomechanics of this tissue. Here, we present a
      staining approach to enhance the contrast of the microstructure in micro-computed
      tomography (micro-CT) imaging as well as a comparison between tissues imaged with
      micro-CT and second harmonic generation (SHG) microscopy. We then apply a
      modified version of Frangi's vesselness filter to automatically segment the
      connective tissue beams of the LC and determine the orientation of each beam.
      This approach successfully segmented the beams of a porcine optic nerve head from
      micro-CT in three dimensions and SHG microscopy in two dimensions. As an
      application of this filter, we present finite-element modelling of the posterior
      eye that suggests that connective tissue volume fraction is the major driving
      factor of LC biomechanics. We conclude that segmentation with Frangi's filter is
      a powerful tool for future image-driven studies of LC biomechanics. 

PMID- 25589573
TI  - Lateral assembly of N-cadherin drives tissue integrity by stabilizing adherens
      junctions.
AB  - Cadherin interactions ensure the correct registry and anchorage of cells during
      tissue formation. Along the plasma membrane, cadherins form inter-junctional
      lattices via cis- and trans-dimerization. While structural studies have provided
      models for cadherin interactions, the molecular nature of cadherin binding in
      vivo remains unexplored. We undertook a multi-disciplinary approach combining
      live cell imaging of three-dimensional cell assemblies (spheroids) with a
      computational model to study the dynamics of N-cadherin interactions. Using a
      loss-of-function strategy, we demonstrate that each N-cadherin interface plays a
      distinct role in spheroid formation. We found that cis-dimerization is not a
      prerequisite for trans-interactions, but rather modulates trans-interfaces to
      ensure tissue stability. Using a model of N-cadherin junction dynamics, we show
      that the absence of cis-interactions results in low junction stability and loss
      of tissue integrity. By quantifying the binding and unbinding dynamics of the N
      cadherin binding interfaces, we determined that mutating either interface results
      in a 10-fold increase in the dissociation constant. These findings provide new
      quantitative information on the steps driving cadherin intercellular adhesion and
      demonstrate the role of cis-interactions in junction stability. 

PMID- 25589574
TI  - Using argument notation to engineer biological simulations with increased
      confidence.
AB  - The application of computational and mathematical modelling to explore the
      mechanics of biological systems is becoming prevalent. To significantly impact
      biological research, notably in developing novel therapeutics, it is critical
      that the model adequately represents the captured system. Confidence in adopting
      in silico approaches can be improved by applying a structured argumentation
      approach, alongside model development and results analysis. We propose an
      approach based on argumentation from safety-critical systems engineering, where a
      system is subjected to a stringent analysis of compliance against identified
      criteria. We show its use in examining the biological information upon which a
      model is based, identifying model strengths, highlighting areas requiring
      additional biological experimentation and providing documentation to support
      model publication. We demonstrate our use of structured argumentation in the
      development of a model of lymphoid tissue formation, specifically Peyer's
      Patches. The argumentation structure is captured using Artoo
      (www.york.ac.uk/ycil/software/artoo), our Web-based tool for constructing fitness
      for-purpose arguments, using a notation based on the safety-critical goal
      structuring notation. We show how argumentation helps in making the design and
      structured analysis of a model transparent, capturing the reasoning behind the
      inclusion or exclusion of each biological feature and recording assumptions, as
      well as pointing to evidence supporting model-derived conclusions. 

PMID- 25589575
TI  - Modelling the propagation of social response during a disease outbreak.
AB  - Epidemic trajectories and associated social responses vary widely between
      populations, with severe reactions sometimes observed. When confronted with fatal
      or novel pathogens, people exhibit a variety of behaviours from anxiety to
      hoarding of medical supplies, overwhelming medical infrastructure and rioting. We
      developed a coupled network approach to understanding and predicting social
      response. We couple the disease spread and panic spread processes and model them
      through local interactions between agents. The social contagion process depends
      on the prevalence of the disease, its perceived risk and a global media signal.
      We verify the model by analysing the spread of disease and social response during
      the 2009 H1N1 outbreak in Mexico City and 2003 severe acute respiratory syndrome
      and 2009 H1N1 outbreaks in Hong Kong, accurately predicting population-level
      behaviour. This kind of empirically validated model is critical to exploring
      strategies for public health intervention, increasing our ability to anticipate
      the response to infectious disease outbreaks. 

PMID- 25589576
TI  - A steering mechanism for phototaxis in Chlamydomonas.
AB  - Chlamydomonas shows both positive and negative phototaxis. It has a single
      eyespot near its equator, and as the cell rotates during the forward motion, the
      light signal received by the eyespot varies. We use a simple mechanical model of
      Chlamydomonas that couples the flagellar beat pattern to the light intensity at
      the eyespot to demonstrate a mechanism for phototactic steering that is
      consistent with observations. The direction of phototaxis is controlled by a
      parameter in our model, and the steering mechanism is robust to noise. Our model
      shows switching between directed phototaxis when the light is on and run-and
      tumble behaviour in the dark. 

PMID- 25589577
TI  - Bacterial genospecies that are not ecologically coherent: population genomics of
      Rhizobium leguminosarum.
AB  - Biological species may remain distinct because of genetic isolation or ecological
      adaptation, but these two aspects do not always coincide. To establish the nature
      of the species boundary within a local bacterial population, we characterized a
      sympatric population of the bacterium Rhizobium leguminosarum by genomic
      sequencing of 72 isolates. Although all strains have 16S rRNA typical of R.
      leguminosarum, they fall into five genospecies by the criterion of average
      nucleotide identity (ANI). Many genes, on plasmids as well as the chromosome,
      support this division: recombination of core genes has been largely within
      genospecies. Nevertheless, variation in ecological properties, including
      symbiotic host range and carbon-source utilization, cuts across these
      genospecies, so that none of these phenotypes is diagnostic of genospecies. This
      phenotypic variation is conferred by mobile genes. The genospecies meet the Mayr
      criteria for biological species in respect of their core genes, but do not
      correspond to coherent ecological groups, so periodic selection may not be
      effective in purging variation within them. The population structure is
      incompatible with traditional 'polyphasic taxonomy' that requires bacterial
      species to have both phylogenetic coherence and distinctive phenotypes. More
      generally, genomics has revealed that many bacterial species share adaptive
      modules by horizontal gene transfer, and we envisage a more consistent taxonomic
      framework that explicitly recognizes this. Significant phenotypes should be
      recognized as 'biovars' within species that are defined by core gene phylogeny. 

PMID- 25589578
TI  - Drosophila gene tao-1 encodes proteins with and without a Ste20 kinase domain
      that affect cytoskeletal architecture and cell migration differently.
AB  - Tao-1, the single representative of the Sterile 20 kinase subfamily in
      Drosophila, is best known for destabilizing microtubules at the actin-rich
      cortex, regulating the cytoskeletal architecture of cells. More recently, Tao-1
      was shown to act in the Salvador-Warts-Hippo pathway by phosphorylating Hippo,
      regulating cell growth as well as cell polarity. Here, we show that tao-1 encodes
      two proteins, one with the Sterile 20 kinase domain (Tao-L) and one without it
      (Tao-S), and that they act in an antagonistic manner. Tao-L expression causes
      lamellipodia-like cell protrusions, whereas Tao-S expression results in filopodia
      like structures that make cells stick to the surface they attach to. Ectopic Tao
      1 expression in the anterior region of Drosophila embryos results in pole cell
      formation as normally observed at the posterior end. Tao-S expression causes
      primordial germ cells (PGCs) to adhere to the inner wall of the gut primordia and
      prevents proper transepithelial migration to the gonads. Conversely, RNAi
      knockdowns of Tao-1 cause disordered migration of PGCs out of the gut epithelium,
      their dispersal within the embryo and cell death. The results reveal a novel
      function of Tao-1 in cell migration, which is based on antagonistic activities of
      two proteins encoded by a single gene. 

PMID- 25589579
TI  - MHJ_0461 is a multifunctional leucine aminopeptidase on the surface of Mycoplasma
      hyopneumoniae.
AB  - Aminopeptidases are part of the arsenal of virulence factors produced by
      bacterial pathogens that inactivate host immune peptides. Mycoplasma
      hyopneumoniae is a genome-reduced pathogen of swine that lacks the genetic
      repertoire to synthesize amino acids and relies on the host for availability of
      amino acids for growth. M. hyopneumoniae recruits plasmin(ogen) onto its cell
      surface via the P97 and P102 adhesins and the glutamyl aminopeptidase MHJ_0125.
      Plasmin plays an important role in regulating the inflammatory response in the
      lungs of pigs infected with M. hyopneumoniae. We show that recombinant MHJ_0461
      (rMHJ_0461) functions as a leucine aminopeptidase (LAP) with broad substrate
      specificity for leucine, alanine, phenylalanine, methionine and arginine and that
      MHJ_0461 resides on the surface of M. hyopneumoniae. rMHJ_0461 also binds
      heparin, plasminogen and foreign DNA. Plasminogen bound to rMHJ_0461 was readily
      converted to plasmin in the presence of tPA. Computational modelling identified
      putative DNA and heparin-binding motifs on solvent-exposed sites around a large
      pore on the LAP hexamer. We conclude that MHJ_0461 is a LAP that moonlights as a
      multifunctional adhesin on the cell surface of M. hyopneumoniae. 

PMID- 25589580
TI  - Spatial and Temporal Control Contribute to Step Length Asymmetry During Split
      Belt Adaptation and Hemiparetic Gait.
AB  - BACKGROUND: Step length asymmetry (SLA) is a common hallmark of gait poststroke.
      Though conventionally viewed as a spatial deficit, SLA can result from
      differences in where the feet are placed relative to the body (step position
      strategy), the timing between foot strikes (step time strategy), or the velocity
      of the body relative to the feet (step velocity strategy). OBJECTIVE: The goal of
      this study was to characterize the relative contributions of each of these
      strategies to SLA. METHODS: We developed an analytical model that parses SLA into
      independent step position, step time, and step velocity contributions. This model
      was validated by reproducing SLA values for 25 healthy participants when their
      natural symmetric gait was perturbed on a split-belt treadmill moving at either a
      2:1 or 3:1 belt-speed ratio. We then applied the validated model to quantify step
      position, step time, and step velocity contributions to SLA in 15 stroke
      survivors while walking at their self-selected speed. RESULTS: SLA was predicted
      precisely by summing the derived contributions, regardless of the belt-speed
      ratio. Although the contributions to SLA varied considerably across our sample of
      stroke survivors, the step position contribution tended to oppose the other 2
      possibly as an attempt to minimize overall SLA. CONCLUSIONS: Our results suggest
      that changes in where the feet are placed or changes in interlimb timing could be
      used as compensatory strategies to reduce overall SLA in stroke survivors. These
      results may allow clinicians and researchers to identify patient-specific gait
      abnormalities and personalize their therapeutic approaches accordingly.

PMID- 25589586
TI  - Navigational path integration by cortical neurons: origins in higher-order
      direction selectivity.
AB  - Navigation relies on the neural processing of sensory cues about observer self
      movement and spatial location. Neurons in macaque dorsal medial superior temporal
      cortex (MSTd) respond to visual and vestibular self-movement cues, potentially
      contributing to navigation and orientation. We moved monkeys on circular paths
      around a room while recording the activity of MSTd neurons. MSTd neurons show a
      variety of sensitivities to the monkey's heading direction, circular path through
      the room, and place in the room. Changing visual cues alters the relative
      prevalence of those response properties. Disrupting the continuity of self
      movement paths through the environment disrupts path selectivity in a manner
      linked to the time course of single neuron responses. We hypothesize that sensory
      cues interact with the spatial and temporal integrative properties of MSTd
      neurons to derive path selectivity for navigational path integration supporting
      spatial orientation. 

PMID- 25589585
TI  - The effect of age on postural and cognitive task performance while using
      vibrotactile feedback.
AB  - Vibrotactile feedback (VTF) has been shown to improve balance performance in
      healthy people and people with vestibular disorders in a single-task experimental
      condition. It is unclear how age-related changes in balance affect the ability to
      use VTF and if there are different attentional requirements for old and young
      adults when using VTF. Twenty younger and 20 older subjects participated in this
      two-visit study to examine the effect of age, VTF, sensory condition, cognitive
      task, duration of time, and visit on postural and cognitive performance. Postural
      performance outcome measures included root mean square of center of pressure
      (COP) and trunk tilt, and cognitive performance was assessed using the reaction
      time (RT) from an auditory choice RT task. The results showed that compared with
      younger adults, older adults had an increase in COP in fixed platform conditions
      when using VTF, although they were able to reduce COP during sway-referenced
      platform conditions. Older adults also did not benefit fully from using VTF in
      their first session. The RTs for the secondary cognitive tasks increased
      significantly while using the VTF in both younger and older adults. Older adults
      had a larger increase compared with younger adults, suggesting that greater
      attentional demands were required in older adults when using VTF information.
      Future training protocols for VTF should take into consideration the effect of
      aging. 

PMID- 25589587
TI  - Nasotemporal ERP differences: evidence for increased inhibition of temporal
      distractors.
AB  - Previous research has demonstrated behavioral advantages for stimuli in the
      temporal relative to the nasal visual hemifield. To investigate whether this
      nasotemporal asymmetry reflects a genuinely attentional bias, we recorded event
      related potentials in a task where participants identified a color-defined target
      digit in one visual hemifield that was accompanied by an irrelevant distractor in
      the opposite hemifield (experiment 1). To dissociate the processing of stimuli in
      nasal and temporal visual hemifields, an eye-patching procedure was used. Targets
      triggered N2pc components that marked their attentional selection. Unexpectedly,
      these N2pc components were larger and emerged earlier for nasal relative to
      temporal targets. Experiment 2 provided evidence that this nasotemporal asymmetry
      for the N2pc is linked to an increased attentional inhibition of temporal
      distractors. Relative to nasal distractors, temporal distractors elicited an
      increased inhibition-related contralateral positivity, resulting in more
      pronounced differences between contralateral and ipsilateral event-related
      potentials on trials with temporal distractors and nasal targets. These results
      provide novel evidence for a genuinely attentional contribution to nasotemporal
      asymmetries and suggest that such asymmetries are associated with top-down
      controlled distractor inhibition.

PMID- 25589589
TI  - Comparative diffusion tractography of corticostriatal motor pathways reveals
      differences between humans and macaques.
AB  - The primate corticobasal ganglia circuits are understood to be segregated into
      parallel anatomically and functionally distinct loops. Anatomical and
      physiological studies in macaque monkeys are summarized as showing that an
      oculomotor loop begins with projections from the frontal eye fields (FEF) to the
      caudate nucleus, and a motor loop begins with projections from the primary motor
      cortex (M1) to the putamen. However, recent functional and structural
      neuroimaging studies of the human corticostriatal system report evidence
      inconsistent with this organization. To obtain conclusive evidence, we directly
      compared the pattern of connectivity between cortical motor areas and the
      striatum in humans and macaques in vivo using probabilistic diffusion
      tractography. In macaques we found that FEF is connected with the head of the
      caudate and anterior putamen, and M1 is connected with more posterior sections of
      the caudate and putamen, corroborating neuroanatomical tract tracing findings.
      However, in humans FEF and M1 are connected to largely overlapping portions of
      posterior putamen and only a small portion of the caudate. These results
      demonstrate that the corticobasal connectivity for the oculomotor and primary
      motor loop is not entirely segregated for primates at a macroscopic level and
      that the description of the anatomical connectivity of corticostriatal motor
      systems in humans does not parallel that of macaques, perhaps because of an
      expansion of prefrontal projections to striatum in humans. 

PMID- 25589588
TI  - Electrogenic properties of the Na+/K+ ATPase control transitions between normal
      and pathological brain states.
AB  - Ionic concentrations fluctuate significantly during epileptic seizures. In this
      study, using a combination of in vitro electrophysiology, computer modeling, and
      dynamical systems analysis, we demonstrate that changes in the potassium and
      sodium intra- and extracellular ion concentrations ([K(+)] and [Na(+)],
      respectively) during seizure affect the neuron dynamics by modulating the outward
      Na(+)/K(+) pump current. First, we show that an increase of the outward
      Na(+)/K(+) pump current mediates termination of seizures when there is a
      progressive increase in the intracellular [Na(+)]. Second, we show that the
      Na(+)/K(+) pump current is crucial in maintaining the stability of the
      physiological network state; a reduction of this current leads to the onset of
      seizures via a positive-feedback loop. We then present a novel dynamical
      mechanism for bursting in neurons with a reduced Na(+)/K(+) pump. Overall, our
      study demonstrates the profound role of the current mediated by Na(+)/K(+) ATPase
      on the stability of neuronal dynamics that was previously unknown. 

PMID- 25589591
TI  - Consequences of biomechanically constrained tasks in the design and
      interpretation of synergy analyses.
AB  - Matrix factorization algorithms are commonly used to analyze muscle activity and
      provide insight into neuromuscular control. These algorithms identify low
      dimensional subspaces, commonly referred to as synergies, which can describe
      variation in muscle activity during a task. Synergies are often interpreted as
      reflecting underlying neural control; however, it is unclear how these analyses
      are influenced by biomechanical and task constraints, which can also lead to low
      dimensional patterns of muscle activation. The aim of this study was to evaluate
      whether commonly used algorithms and experimental methods can accurately identify
      synergy-based control strategies. This was accomplished by evaluating synergies
      from five common matrix factorization algorithms using muscle activations
      calculated from 1) a biomechanically constrained task using a musculoskeletal
      model and 2) without task constraints using random synergy activations. Algorithm
      performance was assessed by calculating the similarity between estimated
      synergies and those imposed during the simulations; similarities ranged from 0
      (random chance) to 1 (perfect similarity). Although some of the algorithms could
      accurately estimate specified synergies without biomechanical or task constraints
      (similarity >0.7), with these constraints the similarity of estimated synergies
      decreased significantly (0.3-0.4). The ability of these algorithms to accurately
      identify synergies was negatively impacted by correlation of synergy activations,
      which are increased when substantial biomechanical or task constraints are
      present. Increased variability in synergy activations, which can be captured
      using robust experimental paradigms that include natural variability in motor
      activation patterns, improved identification accuracy but did not completely
      overcome effects of biomechanical and task constraints. These results demonstrate
      that a biomechanically constrained task can reduce the accuracy of estimated
      synergies and highlight the importance of using experimental protocols with
      physiological variability to improve synergy analyses. 

PMID- 25589590
TI  - Acetylcholine excites neocortical pyramidal neurons via nicotinic receptors.
AB  - The neuromodulator acetylcholine (ACh) shapes neocortical function during sensory
      perception, motor control, arousal, attention, learning, and memory. Here we
      investigate the mechanisms by which ACh affects neocortical pyramidal neurons in
      adult mice. Stimulation of cholinergic axons activated muscarinic and nicotinic
      ACh receptors on pyramidal neurons in all cortical layers and in multiple
      cortical areas. Nicotinic receptor activation evoked short-latency, depolarizing
      postsynaptic potentials (PSPs) in many pyramidal neurons. Nicotinic receptor
      mediated PSPs promoted spiking of pyramidal neurons. The duration of the increase
      in spiking was membrane potential dependent, with nicotinic receptor activation
      triggering persistent spiking lasting many seconds in neurons close to threshold.
      Persistent spiking was blocked by intracellular BAPTA, indicating that nicotinic
      ACh receptor activation evoked persistent spiking via a long-lasting calcium
      activated depolarizing current. We compared nicotinic PSPs in primary motor
      cortex (M1), prefrontal cortex (PFC), and visual cortex. The laminar pattern of
      nicotinic excitation was not uniform but was broadly similar across areas, with
      stronger modulation in deep than superficial layers. Superimposed on this broad
      pattern were local differences, with nicotinic PSPs being particularly large and
      common in layer 5 of M1 but not layer 5 of PFC or primary visual cortex (V1).
      Hence, in addition to modulating the excitability of pyramidal neurons in all
      layers via muscarinic receptors, synaptically released ACh preferentially
      increases the activity of deep-layer neocortical pyramidal neurons via nicotinic
      receptors, thereby adding laminar selectivity to the widespread enhancement of
      excitability mediated by muscarinic ACh receptors. 

PMID- 25589592
TI  - The lateral septum as a regulator of hippocampal theta oscillations and defensive
      behavior in rats.
AB  - Hippocampal theta oscillations are linked to various processes, including
      locomotion, learning and memory, and defense and affect. The lateral septum (LS)
      has been implicated in the generation of the hippocampal theta rhythm, but its
      precise role in this process is not well understood. Here, we investigated the
      effects of direct pharmacological inhibition or disinhibition of the dorsal LS
      (dLS) on the frequency of hippocampal theta activity elicited by stimulation of
      the reticular formation in urethane-anesthetized rats. We found that bilateral
      infusions of the GABAA receptor agonist muscimol into the dLS significantly
      increased theta frequency. Strikingly, intra-dLS infusions of the GABAA receptor
      antagonist GABAzine largely abolished reticularly elicited theta activity. We
      also locally injected these same compounds into the medial septum (MS) to test
      for neuroanatomical specificity. In contrast to the effects seen in the dLS,
      intra-MS infusions of muscimol had no effect on theta frequency, whereas intra-MS
      infusions of GABAzine increased theta frequency. Given the hypothesized role of
      hippocampal theta in behavioral defense, we also examined the effects of intra
      dLS application of muscimol in two models of anxiety, the elevated plus maze and
      the novelty-induced suppression of feeding paradigm; both tests revealed clear,
      anxiolytic-like effects following muscimol infusions. The fact that dLS-muscimol
      increased theta frequency while also reducing anxiety-like behaviors challenges
      the influential theta suppression model of anxiolysis, which predicts a slowing
      of theta with anxiolytic compounds. More importantly, the experiments reveal a
      novel role of the LS, especially its dorsal aspects, as an important gating
      mechanism for the expression of theta oscillations in the rodent hippocampus.

PMID- 25589594
TI  - The human motor system alters its reaching movement plan for task-irrelevant,
      positional forces.
AB  - The minimum intervention principle and the uncontrolled manifold hypothesis state
      that our nervous system only responds to force perturbations and sensorimotor
      noise if they affect task success. This idea has been tested in muscle and joint
      coordinate frames and more recently using workspace redundancy (e.g., reaching to
      large targets). However, reaching studies typically involve spatial and or
      temporal constraints. Constrained reaches represent a small proportion of
      movements we perform daily and may limit the emergence of natural behavior. Using
      more relaxed constraints, we conducted two reaching experiments to test the
      hypothesis that humans respond to task-relevant forces and ignore task-irrelevant
      forces. We found that participants responded to both task-relevant and 
      irrelevant forces. Interestingly, participants experiencing a task-irrelevant
      force, which simply pushed them into a different area of a large target and had
      no bearing on task success, changed their movement trajectory prior to being
      perturbed. These movement trajectory changes did not counteract the task
      irrelevant perturbations, as shown in previous research, but rather were made
      into new areas of the workspace. A possible explanation for this behavior change
      is that participants were engaging in active exploration. Our data have
      implications for current models and theories on the control of biological motion.

PMID- 25589595
TI  - Coding of relative size in monkey inferotemporal cortex.
AB  - We seldom mistake a closer object as being larger, even though its retinal image
      is bigger. One underlying mechanism could be to calculate the size of the retinal
      image relative to that of another nearby object. Here we set out to investigate
      whether single neurons in the monkey inferotemporal cortex (IT) are sensitive to
      the relative size of parts in a display. Each neuron was tested on shapes
      containing two parts that could be conjoined or spatially separated. Each shape
      was presented in four versions created by combining the two parts at each of two
      possible sizes. In this design, neurons sensitive to the absolute size of parts
      would show the greatest response modulation when both parts are scaled up,
      whereas neurons encoding relative size would show similar responses. Our main
      findings are that 1) IT neurons responded similarly to all four versions of a
      shape, but tuning tended to be more consistent between versions with
      proportionately scaled parts; 2) in a subpopulation of cells, we observed
      interactions that resulted in similar responses to proportionately scaled parts;
      3) these interactions developed together with sensitivity to absolute size for
      objects with conjoined parts but developed slightly later for objects with
      spatially separate parts. Taken together, our results demonstrate for the first
      time that there is a subpopulation of neurons in IT that encodes the relative
      size of parts in a display, forming a potential neural substrate for size
      constancy. 

PMID- 25589596
TI  - Explaining attention-related changes in behavior and electroencephalography data
      through computational modeling.
AB  - In a recent article, Itthipuripat and colleagues combined psychophysics,
      neurophysiology, and mathematical modeling to investigate the neural mechanism
      underlying behavioral benefits of spatial attention (Itthipuripat S, Ester EF,
      Deering S, Serences JT. J Neurosci 34: 13384-13398, 2014). They found that
      attention-related effects on behavior as well as neural signals could be better
      explained by a response gain model than by a noise reduction model or an
      efficient read-out model. In this Neuro Forum we discuss these results and raise
      several interesting questions and potential interpretations. 

PMID- 25589597
TI  - Compression regimes after endovenous ablation for superficial venous
      insufficiency--A survey of members of the Vascular Society of Great Britain and
      Ireland.
AB  - INTRODUCTION: The optimal compression regime following ultrasound guided foam
      sclerotherapy (UGFS), radiofrequency ablation (RFA) and endovenous laser ablation
      (EVLA) for varicose veins is not known. The aim of this study was to document
      current practice. METHODS: Postal questionnaire sent to 348 consultant members of
      the Vascular Society of Great Britain and Ireland. RESULTS: Valid replies were
      received from 41% (n = 141) surgeons representing at least 68 (61%) vascular
      units. UGFS was used by 74% surgeons, RFA by 70% and EVLA by 32%, but fewer
      patients received UGFS (median 30) annually, than endothermal treatment (median
      50)--P = 0.019. All surgeons prescribed compression: following UGFS for median
      seven days (range two days to three months) and after endothermal ablation for 10
      days (range two days to six weeks)--P = 0.298. Seven different combinations of
      bandages, pads and compression stockings were reported following UGFS and four
      after endothermal ablation. Some surgeons advised changing from bandages to
      stockings from five days (range 1-14) after UGFS. Following endothermal ablation,
      71% used bandages only, followed by compression stockings after two days (range 1
      14). The majority of surgeons (87%) also treated varicose tributaries: 65% used
      phlebectomy, the majority (65%) synchronously with endothermal ablation.
      Concordance of compression regimes between surgeons within vascular units was
      uncommon. Only seven units using UGFS and six units using endothermal ablation
      had consistent compression regimes. CONCLUSION: Compression regimes after
      treatments for varicose veins vary significantly: more evidence is needed to
      guide practice.

PMID- 25589593
TI  - Magnetic resonance imaging demonstrates compartmental muscle mechanisms of human
      vertical fusional vergence.
AB  - Vertical fusional vergence (VFV) normally compensates for slight vertical
      heterophorias. We employed magnetic resonance imaging to clarify extraocular
      muscle contributions to VFV induced by monocular two-prism diopter (1.15 degrees
      ) base-up prism in 14 normal adults. Fusion during prism viewing requires
      monocular infraduction. Scans were repeated without prism, and with prism shifted
      contralaterally. Contractility indicated by morphometric indexes was separately
      analyzed in medial and lateral vertical rectus and superior oblique (SO) putative
      compartments, and superior and inferior horizontal rectus extraocular muscle
      putative compartments, but in the whole inferior oblique (IO). Images confirmed
      appropriate VFV that was implemented by the inferior rectus (IR) medial
      compartment contracting ipsilateral and relaxing contralateral to prism. There
      was no significant contractility in the IR lateral compartment. The superior but
      not inferior lateral rectus (LR) compartment contracted significantly in the
      prism viewing eye, but not contralateral to prism. The IO contracted ipsilateral
      but not contralateral to the prism. In the infraducting eye, the SO medial
      compartment relaxed significantly, while the lateral compartment was unchanged;
      contralateral to prism, the SO lateral compartment contracted, while the medial
      compartment was unchanged. There was no contractility in the superior or medial
      rectus muscles in either eye. There was no globe retraction. We conclude that the
      vertical component of VFV is primarily implemented by IR medial compartment
      contraction. Since appropriate vertical rotation is not directly implemented, or
      is opposed, by associated differential LR and SO compartmental activity, and IO
      contraction, these actions probably implement a torsional component of VFV.

PMID- 25589598
TI  - Gendered Facial Cues Influence Race Categorizations.
AB  - Race and gender categories, although long presumed to be perceived independently,
      are inextricably tethered in social perception due in part to natural confounding
      of phenotypic cues. We predicted that target gender would affect race
      categorizations. Consistent with this hypothesis, feminine faces compelled White
      categorizations, and masculine faces compelled Asian or Black categorizations of
      racially ambiguous targets (Study 1), monoracial targets (Study 2), and real
      facial photographs (Study 3). The efficiency of judgments varied concomitantly.
      White categorizations were rendered more rapidly for feminine, relative to
      masculine faces, but the opposite was true for Asian and Black categorizations
      (Studies 1-3). Moreover, the effect of gender on categorization efficiency was
      compelled by racial phenotypicality for Black targets (Study 3). Finally, when
      targets' race prototypicality was held constant, gender still influenced race
      categorizations (Study 4). These findings indicate that race categorizations are
      biased by presumably unrelated gender cues.

PMID- 25589599
TI  - Constructing rich false memories of committing crime.
AB  - Memory researchers long have speculated that certain tactics may lead people to
      recall crimes that never occurred, and thus could potentially lead to false
      confessions. This is the first study to provide evidence suggesting that full
      episodic false memories of committing crime can be generated in a controlled
      experimental setting. With suggestive memory-retrieval techniques, participants
      were induced to generate criminal and noncriminal emotional false memories, and
      we compared these false memories with true memories of emotional events. After
      three interviews, 70% of participants were classified as having false memories of
      committing a crime (theft, assault, or assault with a weapon) that led to police
      contact in early adolescence and volunteered a detailed false account. These
      reported false memories of crime were similar to false memories of noncriminal
      events and to true memory accounts, having the same kinds of complex descriptive
      and multisensory components. It appears that in the context of a highly
      suggestive interview, people can quite readily generate rich false memories of
      committing crime.

PMID- 25589600
TI  - Loss of migratory behaviour increases infection risk for a butterfly host.
AB  - Long-distance animal migrations have important consequences for infectious
      disease dynamics. In some cases, migration lowers pathogen transmission by
      removing infected individuals during strenuous journeys and allowing animals to
      periodically escape contaminated habitats. Human activities are now causing some
      migratory animals to travel shorter distances or form sedentary (non-migratory)
      populations. We focused on North American monarch butterflies and a specialist
      protozoan parasite to investigate how the loss of migratory behaviours affects
      pathogen spread and evolution. Each autumn, monarchs migrate from breeding
      grounds in the eastern US and Canada to wintering sites in central Mexico.
      However, some monarchs have become non-migratory and breed year-round on exotic
      milkweed in the southern US. We used field sampling, citizen science data and
      experimental inoculations to quantify infection prevalence and parasite virulence
      among migratory and sedentary populations. Infection prevalence was markedly
      higher among sedentary monarchs compared with migratory monarchs, indicating that
      diminished migration increases infection risk. Virulence differed among parasite
      strains but was similar between migratory and sedentary populations, potentially
      owing to high gene flow or insufficient time for evolutionary divergence. More
      broadly, our findings suggest that human activities that alter animal migrations
      can influence pathogen dynamics, with implications for wildlife conservation and
      future disease risks. 

PMID- 25589601
TI  - The oldest parareptile and the early diversification of reptiles.
AB  - Amniotes, tetrapods that evolved the cleidoic egg and thus independence from
      aquatic larval stages, appeared ca 314 Ma during the Coal Age. The rapid
      diversification of amniotes and other tetrapods over the course of the Late
      Carboniferous period was recently attributed to the fragmentation of coal-swamp
      rainforests ca 307 Ma. However, the amniote fossil record during the
      Carboniferous is relatively sparse, with ca 33% of the diversity represented by
      single specimens for each species. We describe here a new species of reptilian
      amniote that was collected from uppermost Carboniferous rocks of Prince Edward
      Island, Canada. Erpetonyx arsenaultorum gen. et sp. nov. is a new parareptile
      distinguished by 29 presacral vertebrae and autapomorphies of the carpus.
      Phylogenetic analyses of parareptiles reveal E. arsenaultorum as the closest
      relative of bolosaurids. Stratigraphic calibration of our results indicates that
      parareptiles began their evolutionary radiation before the close of the
      Carboniferous Period, and that the diversity of end-Carboniferous reptiles is 80%
      greater than suggested by previous work. Latest Carboniferous reptiles were still
      half as diverse as synapsid amniotes, a disparity that may be attributable to
      preservational biases, to collecting biases, to the origin of herbivory in
      tetrapods or any combination of these factors. 

PMID- 25589602
TI  - Space race functional responses.
AB  - We derive functional responses under the assumption that predators and prey are
      engaged in a space race in which prey avoid patches with many predators and
      predators avoid patches with few or no prey. The resulting functional response
      models have a simple structure and include functions describing how the
      emigration of prey and predators depend on interspecific densities. As such, they
      provide a link between dispersal behaviours and community dynamics. The derived
      functional response is general but is here modelled in accordance with
      empirically documented emigration responses. We find that the prey emigration
      response to predators has stabilizing effects similar to that of the DeAngelis
      Beddington functional response, and that the predator emigration response to prey
      has destabilizing effects similar to that of the Holling type II response. A
      stability criterion describing the net effect of the two emigration responses on
      a Lotka-Volterra predator-prey system is presented. The winner of the space race
      (i.e. whether predators or prey are favoured) is determined by the relationship
      between the slopes of the species' emigration responses. It is predicted that
      predators win the space race in poor habitats, where predator and prey densities
      are low, and that prey are more successful in richer habitats. 

PMID- 25589603
TI  - Ecology of information: social transmission dynamics within groups of non-social
      insects.
AB  - While many studies focus on how animals use public information, the dynamics of
      information spread and maintenance within groups, i.e. the 'ecology of
      information', have received little attention. Here we use fruitflies trained to
      lay eggs on specific substrates to implement information into groups containing
      both trained and untrained individuals. We quantify inter-individual interactions
      and then measure the spread of oviposition preference with behavioural tests.
      Untrained individuals increase their interactive approaches in the presence of
      trained individuals, and the oviposition preference transmission is directly
      proportional to how much trained and untrained individuals interact.
      Unexpectedly, the preference of trained individuals to their trained oviposition
      substrate decreases after interactions with untrained individuals, leading to an
      overall informational loss. This shows that social learning alone is not enough
      to support informational stability. 

PMID- 25589604
TI  - How to catch more prey with less effective traps: explaining the evolution of
      temporarily inactive traps in carnivorous pitcher plants.
AB  - Carnivorous Nepenthes pitcher plants capture arthropods with specialized slippery
      surfaces. The key trapping surface, the pitcher rim (peristome), is highly
      slippery when wetted by rain, nectar or condensation, but not when dry. As
      natural selection should favour adaptations that maximize prey intake, the
      evolution of temporarily inactive traps seems paradoxical. Here, we show that
      intermittent trap deactivation promotes 'batch captures' of ants. Prey surveys
      revealed that N. rafflesiana pitchers sporadically capture large numbers of ants
      from the same species. Continuous experimental wetting of the peristome increased
      the number of non-recruiting prey, but decreased the number of captured ants and
      shifted their trapping mode from batch to individual capture events. Ant
      recruitment was also lower to continuously wetted pitchers. Our experimental data
      fit a simple model that predicts that intermittent, wetness-based trap activation
      should allow safe access for 'scout' ants under dry conditions, thereby promoting
      recruitment and ultimately higher prey numbers. The peristome trapping mechanism
      may therefore represent an adaptation for capturing ants. The relatively rare
      batch capture events may particularly benefit larger plants with many pitchers.
      This explains why young plants of many Nepenthes species additionally employ
      wetness-independent, waxy trapping surfaces. 

PMID- 25589605
TI  - Why inclusive fitness can make it adaptive to produce less fit extra-pair
      offspring.
AB  - Social monogamy predominates in avian breeding systems, but most socially
      monogamous species engage in promiscuous extra-pair copulations (EPCs). The
      reasons behind this remain debated, and recent empirical work has uncovered
      patterns that do not seem to fit existing hypotheses. In particular, some results
      seem to contradict the inbreeding avoidance hypothesis: females can prefer extra
      pair partners that are more closely related to them than their social partners,
      and extra-pair young can have lower fitness than within-pair young. Motivated by
      these studies, we show that such results can become explicable when an asymmetry
      in inbreeding tolerance between monogamy and polygamy is extended to species that
      combine both strategies within a single reproductive season. Under fairly general
      conditions, it can be adaptive for a female to choose an unrelated social
      partner, but inbreed with an extra-pair partner. Inbreeding depression is
      compensated for by inclusive fitness benefits, which are only fully realized in
      EPCs. We also show that if a female has already formed a suboptimal social bond,
      there are scenarios where it is beneficial to engage in EPCs with less related
      males, and others where EPCs with more related males increase her inclusive
      fitness. This has implications for detecting general relatedness or fitness
      trends when averaged over several species. 

PMID- 25589606
TI  - Chimpanzees trust conspecifics to engage in low-cost reciprocity.
AB  - Many of humans' most important social interactions rely on trust, including most
      notably among strangers. But little is known about the evolutionary roots of
      human trust. We presented chimpanzees (Pan troglodytes) with a modified version
      of the human trust game--trust in reciprocity--in which subjects could opt either
      to obtain a small but safe reward on their own or else to send a larger reward to
      a partner and trust her to reciprocate a part of the reward that she could not
      access herself. In a series of three studies, we found strong evidence that in
      interacting with a conspecific, chimpanzees show spontaneous trust in a novel
      context; flexibly adjust their level of trust to the trustworthiness of their
      partner and develop patterns of trusting reciprocity over time. At least in some
      contexts then, trust in reciprocity is not unique to humans, but rather has its
      evolutionary roots in the social interactions of humans' closest primate
      relatives.

PMID- 25589607
TI  - Symbiodinium identity alters the temperature-dependent settlement behaviour of
      Acropora millepora coral larvae before the onset of symbiosis.
AB  - The global distribution of marine species, many of which disperse during the
      larval stages, is influenced by ocean temperature regimes. Here, we test how
      temperature and the coral symbionts (Symbiodinium) affect survival, symbiont
      uptake, settlement success and habitat choice of Acropora millepora larvae.
      Experiments were conducted at Heron Island (Australia), where larvae were exposed
      to 22.5, 24.5, 26.5 and 28.5 degrees C. Within each temperature treatment, larvae
      were offered symbionts with distinct characteristics: (i) homologous Symbiodinium
      type C3, (ii) regionally homologous thermo-tolerant type D1, and (iii)
      heterologous thermo-tolerant type C15, as well as controls of (iv) un-filtered
      and (v) filtered seawater. Results show that lower instead of higher temperatures
      adversely affected recruitment by reducing larval survival and settlement. Low
      temperatures also reduced recruit habitat choice and initial symbiont densities,
      both of which impact on post-settlement survival. At lower temperatures, larvae
      increasingly settle away from preferred vertical surfaces and not on crustose
      coralline algae (CCA). Surprisingly, substrate preference to CCA was modified by
      the presence of specific symbiont genotypes that were present ex-hospite (outside
      the coral larvae). When different symbionts were mixed, the outcomes were non
      additive, indicating that symbiont interactions modify the response. We propose
      that the observed influence of ex-hospite symbionts on settlement behaviour may
      have evolved through ecological facilitation and the study highlights the
      importance of biological processes during coral settlement. 

PMID- 25589608
TI  - A phylogenetic backbone for Bivalvia: an RNA-seq approach.
AB  - Bivalves are an ancient and ubiquitous group of aquatic invertebrates with an
      estimated 10 000-20 000 living species. They are economically significant as a
      human food source, and ecologically important given their biomass and effects on
      communities. Their phylogenetic relationships have been studied for decades, and
      their unparalleled fossil record extends from the Cambrian to the Recent.
      Nevertheless, a robustly supported phylogeny of the deepest nodes, needed to
      fully exploit the bivalves as a model for testing macroevolutionary theories, is
      lacking. Here, we present the first phylogenomic approach for this important
      group of molluscs, including novel transcriptomic data for 31 bivalves obtained
      through an RNA-seq approach, and analyse these data with published genomes and
      transcriptomes of other bivalves plus outgroups. Our results provide a well
      resolved, robust phylogenetic backbone for Bivalvia with all major lineages
      delineated, addressing long-standing questions about the monophyly of
      Protobranchia and Heterodonta, and resolving the position of particular groups
      such as Palaeoheterodonta, Archiheterodonta and Anomalodesmata. This now fully
      resolved backbone demonstrates that genomic approaches using hundreds of genes
      are feasible for resolving phylogenetic questions in bivalves and other animals. 

PMID- 25589609
TI  - Payoff-based learning explains the decline in cooperation in public goods games.
AB  - Economic games such as the public goods game are increasingly being used to
      measure social behaviours in humans and non-human primates. The results of such
      games have been used to argue that people are pro-social, and that humans are
      uniquely altruistic, willingly sacrificing their own welfare in order to benefit
      others. However, an alternative explanation for the empirical observations is
      that individuals are mistaken, but learn, during the game, how to improve their
      personal payoff. We test between these competing hypotheses, by comparing the
      explanatory power of different behavioural rules, in public goods games, where
      individuals are given different amounts of information. We find: (i) that
      individual behaviour is best explained by a learning rule that is trying to
      maximize personal income; (ii) that conditional cooperation disappears when the
      consequences of cooperation are made clearer; and (iii) that social preferences,
      if they exist, are more anti-social than pro-social. 

PMID- 25589611
TI  - Gut Feeling in AKI: The Long Arm of Short-Chain Fatty Acids.

PMID- 25589610
TI  - Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides.
AB  - Progressive CKD is generally detected at a late stage by a sustained decline in
      eGFR and/or the presence of significant albuminuria. With the aim of early and
      improved risk stratification of patients with CKD, we studied urinary peptides in
      a large cross-sectional multicenter cohort of 1990 individuals, including 522
      with follow-up data, using proteome analysis. We validated that a previously
      established multipeptide urinary biomarker classifier performed significantly
      better in detecting and predicting progression of CKD than the current clinical
      standard, urinary albumin. The classifier was also more sensitive for identifying
      patients with rapidly progressing CKD. Compared with the combination of baseline
      eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the
      multipeptide biomarker classifier significantly improved CKD risk prediction
      (AUC=0.831) as assessed by the net reclassification index (0.303+/--0.065;
      P<0.001) and integrated discrimination improvement (0.058+/-0.014; P<0.001).
      Correlation of individual urinary peptides with CKD stage and progression showed
      that the peptides that associated with CKD, irrespective of CKD stage or CKD
      progression, were either fragments of the major circulating proteins, suggesting
      failure of the glomerular filtration barrier sieving properties, or different
      collagen fragments, suggesting accumulation of intrarenal extracellular matrix.
      Furthermore, protein fragments associated with progression of CKD originated
      mostly from proteins related to inflammation and tissue repair. Results of this
      study suggest that urinary proteome analysis might significantly improve the
      current state of the art of CKD detection and outcome prediction and that
      identification of the urinary peptides allows insight into various ongoing
      pathophysiologic processes in CKD.

PMID- 25589613
TI  - Can the Urinary Peptidome Outperform Creatinine and Albumin to Predict Renal
      Function Decline?

PMID- 25589612
TI  - Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion.
AB  - Short-chain fatty acids (SCFAs) are fermentation end products produced by the
      intestinal microbiota and have anti-inflammatory and histone deacetylase
      inhibiting properties. Recently, a dual relationship between the intestine and
      kidneys has been unraveled. Therefore, we evaluated the role of SCFA in an AKI
      model in which the inflammatory process has a detrimental role. We observed that
      therapy with the three main SCFAs (acetate, propionate, and butyrate) improved
      renal dysfunction caused by injury. This protection was associated with low
      levels of local and systemic inflammation, oxidative cellular stress, cell
      infiltration/activation, and apoptosis. However, it was also associated with an
      increase in autophagy. Moreover, SCFAs inhibited histone deacetylase activity and
      modulated the expression levels of enzymes involved in chromatin modification. In
      vitro analyses showed that SCFAs modulated the inflammatory process, decreasing
      the maturation of dendritic cells and inhibiting the capacity of these cells to
      induce CD4(+) and CD8(+) T cell proliferation. Furthermore, SCFAs ameliorated the
      effects of hypoxia in kidney epithelial cells by improving mitochondrial
      biogenesis. Notably, mice treated with acetate-producing bacteria also had better
      outcomes after AKI. Thus, we demonstrate that SCFAs improve organ function and
      viability after an injury through modulation of the inflammatory process, most
      likely via epigenetic modification.

PMID- 25589615
TI  - Potential role of pNF-H, a biomarker of axonal damage in the central nervous
      system, as a predictive marker of chemotherapy-induced cognitive impairment.
AB  - PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a clinically
      significant problem. Previous studies using magnetic resonance imaging indicated
      structural changes in the cerebral white matter of patients with CICI.
      Phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in
      axons, was recently reported to be elevated in the serum of patients with some
      central nervous system disorders. We performed a cross-sectional analysis of
      neuropsychological test results and serum pNF-H levels in patients undergoing
      adjuvant chemotherapy for breast cancer. Our hypothesis was that CICI is
      accompanied by axonal damage that can be detected by elevated serum pNF-H levels.
      EXPERIMENTAL DESIGN: Seventy-six patients with early breast cancer in various
      phases of treatment (naive to chemotherapy; after one, three, or seven cycles of
      chemotherapy; or with a history of chemotherapy) were assessed by self
      administered neuropsychological tests and a single pNF-H measurement. The chi(2)
      and Mann-Whitney tests were used for statistical analysis. RESULTS: Increased pNF
      H levels were observed in 28.8% of the patients who underwent chemotherapy, but
      in none of the chemotherapy-naive patients or patients with a history of
      chemotherapy. The pNF-H-positive rate increased significantly in proportion to
      the number of chemotherapy cycles (one cycle, 5.0%; three cycles, 31.6%; seven
      cycles, 55.0%; P < 0.05). No significant differences in neuropsychological test
      results were observed among the groups. CONCLUSIONS: The serum pNF-H level in
      patients undergoing chemotherapy for breast cancer increased in a cumulative dose
      dependent manner, suggesting its potential application as a biomarker of neural
      damage after chemotherapy.

PMID- 25589616
TI  - Interleukin-6 as a therapeutic target.
AB  - Human IL6 is a cytokine produced by many cell types that has pleiotropic effects.
      In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase
      proteins, and anemia and has antiangiogenic effects. Blocking IL6 has
      demonstrated therapeutic efficacy with drug registration in Castleman disease and
      inflammatory diseases (rheumatoid arthritis) without major toxicity.
      Interestingly, the inhibition of C-reactive protein (CRP) production is a
      trustworthy surrogate marker of anti-IL6 therapy efficacy. Clinically registered
      IL6 inhibitors include siltuximab, an anti-IL6 mAb, and tocilizumab, an anti-IL6R
      mAb. In various cancers, in particular plasma cell cancers, large randomized
      trials showed no efficacy of IL6 inhibitors, despite a full inhibition of CRP
      production in treated patients in vivo, the numerous data showing an involvement
      of IL6 in these diseases, and initial short-term treatments demonstrating a
      dramatic inhibition of cancer cell proliferation in vivo. A likely explanation is
      the plasticity of cancer cells, with the presence of various subclones, making
      the outgrowth of cancer subclones possible using growth factors other than IL6.
      In addition, current therapeutic strategies used in these cancers already target
      IL6 activity. Thus, anti-IL6 therapeutics are able to neutralize IL6 production
      in vivo and are safe and useful in inflammatory diseases and Castleman disease.

PMID- 25589614
TI  - Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal
      Cancer.
AB  - PURPOSE: VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach
      for patients with metastatic renal cell carcinoma (RCC). However, resistance to
      treatment is inevitable. Identification of novel targets could lead to better
      treatment for patients with TKI-naive or -resistant RCC. EXPERIMENTAL DESIGN: In
      this study, we performed transcriptome analysis of VEGFR TKI-resistant tumors in
      a murine model and discovered that the SPHK-S1P pathway is upregulated at the
      time of resistance. We tested sphingosine-1-phosphate (S1P) pathway inhibition
      using an anti-S1P mAb (sphingomab), in two mouse xenograft models of RCC, and
      assessed tumor SPHK expression and S1P plasma levels in patients with metastatic
      RCC. RESULTS: Resistant tumors expressed several hypoxia-regulated genes. The
      SPHK1 pathway was among the most highly upregulated pathways that accompanied
      resistance to VEGFR TKI therapy. SPHK1 was expressed in human RCC, and the
      product of SPHK1 activity, S1P, was elevated in patients with metastatic RCC,
      suggesting that human RCC behavior could, in part, be due to overproduction of
      S1P. Sphingomab neutralization of extracellular S1P slowed tumor growth in both
      mouse models. Mice bearing tumors that had developed resistance to sunitinib
      treatment also exhibited tumor growth suppression with sphingomab. Sphingomab
      treatment led to a reduction in tumor blood flow as measured by MRI. CONCLUSIONS:
      Our findings suggest that S1P inhibition may be a novel therapeutic strategy in
      patients with treatment-naive RCC and also in the setting of resistance to VEGFR
      TKI therapy.

PMID- 25589617
TI  - A comparative study of molecular characteristics of diffuse large B-cell lymphoma
      from patients with and without human immunodeficiency virus infection.
AB  - PURPOSE: HIV-related diffuse large B-cell lymphoma (DLBCL) may be biologically
      different from DLBCL in the general population. We compared, by HIV status, the
      expression and prognostic significance of selected oncogenic markers in DLBCL
      diagnosed at Kaiser Permanente in California, between 1996 and 2007. EXPERIMENTAL
      DESIGN: Eighty HIV-infected DLBCL patients were 1:1 matched to 80 HIV-uninfected
      DLBCL patients by age, gender, and race. Twenty-three markers in the following
      categories were examined using IHC: (i) cell-cycle regulators, (ii) B-cell
      activators, (iii) antiapoptotic proteins, and (iv) others, such as IgM. Tumor
      marker expression was compared across HIV infection status by Fisher exact test.
      For markers differentially expressed in HIV-related DLBCL, logistic regression
      was used to evaluate the association between tumor marker expression and 2-year
      overall mortality, adjusting for International Prognostic Index, cell-of-origin
      phenotype, and DLBCL morphologic variants. RESULTS: Expression of cMYC (%
      positive in HIV-related and -unrelated DLBCL: 64% vs. 32%), BCL6 (45% vs. 10%),
      PKC-beta2 (61% vs. 4%), MUM1 (59% vs. 14%), and CD44 (87% vs. 56%) was
      significantly elevated in HIV-related DLBCLs, whereas expression of p27 (39% vs.
      75%) was significantly reduced. Of these, cMYC expression was independently
      associated with increased 2-year mortality in HIV-infected patients [relative
      risk = 3.09 (0.90-10.55)] in multivariable logistic regression. CONCLUSIONS:
      These results suggest that HIV-related DLBCL pathogenesis more frequently
      involves cMYC and BCL6 among other factors. In particular, cMYC-mediated
      pathogenesis may partly explain the more aggressive clinical course of DLBCL in
      HIV-infected patients.

PMID- 25589618
TI  - Genomic analysis of metastatic cutaneous squamous cell carcinoma.
AB  - PURPOSE: A rare 5% of cutaneous squamous cell carcinomas (cSCC) metastasize, lack
      FDA-approved therapies, and carry a poor prognosis. Our aim was to identify
      recurrent genomic alterations in this little-studied population of metastatic
      cSCCs. EXPERIMENTAL DESIGN: We performed targeted sequencing of 504 cancer
      associated genes on lymph node metastases in 29 patients with cSCC and identified
      mutations and somatic copy-number alterations associated with metastatic cSCC. We
      determined significantly mutated, deleted, and amplified genes and associated
      genomic alterations with clinical variables. RESULTS: The cSCC genome is
      heterogeneous with widely varying numbers of genomic alterations and does not
      appear to be associated with human papillomavirus. We found previously identified
      recurrently altered genes (TP53, CDKN2A, NOTCH1/2) but also a wide spectrum of
      oncogenic mutations affecting RAS/RTK/PI3K, squamous differentiation, cell cycle,
      and chromatin remodeling pathway genes. Specific mutations in known oncogenic
      drivers and pathways were correlated with inferior patient outcomes. Our results
      suggest potential therapeutic targets in metastatic cSCC, including PIK3CA,
      FGFR3, BRAF, and EGFR, similar to those reported in SCCs of the lung and head and
      neck, suggesting that clinical trials could be developed to accrue patients with
      SCCs from multiple sites of origin. CONCLUSIONS: We have genomically
      characterized a rare cohort of 29 metastatic cSCCs and identified a diverse array
      of oncogenic alterations that can guide future studies of this disease.

PMID- 25589619
TI  - The BRAF and MEK Inhibitors Dabrafenib and Trametinib: Effects on Immune Function
      and in Combination with Immunomodulatory Antibodies Targeting PD-1, PD-L1, and
      CTLA-4.
AB  - PURPOSE: To assess the immunologic effects of dabrafenib and trametinib in vitro
      and to test whether trametinib potentiates or antagonizes the activity of
      immunomodulatory antibodies in vivo. EXPERIMENTAL DESIGN: Immune effects of
      dabrafenib and trametinib were evaluated in human CD4(+) and CD8(+) T cells from
      healthy volunteers, a panel of human tumor cell lines, and in vivo using a CT26
      mouse model. RESULTS: Dabrafenib enhanced pERK expression levels and did not
      suppress human CD4(+) or CD8(+) T-cell function. Trametinib reduced pERK levels,
      and resulted in partial/transient inhibition of T-cell proliferation/expression
      of a cytokine and immunomodulatory gene subset, which is context dependent.
      Trametinib effects were partially offset by adding dabrafenib. Dabrafenib and
      trametinib in BRAF V600E/K, and trametinib in BRAF wild-type tumor cells induced
      apoptosis markers, upregulated HLA molecule expression, and downregulated certain
      immunosuppressive factors such as PD-L1, IL1, IL8, NT5E, and VEGFA. PD-L1
      expression in tumor cells was upregulated after acquiring resistance to BRAF
      inhibition in vitro. Combinations of trametinib with immunomodulators targeting
      PD-1, PD-L1, or CTLA-4 in a CT26 model were more efficacious than any single
      agent. The combination of trametinib with anti-PD-1 increased tumor-infiltrating
      CD8(+) T cells in CT26 tumors. Concurrent or phased sequential treatment, defined
      as trametinib lead-in followed by trametinib plus anti-PD-1 antibody,
      demonstrated superior efficacy compared with anti-PD-1 antibody followed by anti
      PD-1 plus trametinib. CONCLUSION: These findings support the potential for
      synergy between targeted therapies dabrafenib and trametinib and immunomodulatory
      antibodies. Clinical exploration of such combination regimens is under way.

PMID- 25589620
TI  - Pharmacogenetic Analysis of INT 0144 Trial: Association of Polymorphisms with
      Survival and Toxicity in Rectal Cancer Patients Treated with 5-FU and Radiation.
AB  - PURPOSE: We tested whether 18 polymorphisms in 16 genes (GSTP1, COX2, IL10, EGFR,
      EGF, FGFR4, CCDN1, VEGFR2, VEGF, CXCR2, IL8, MMP3, ICAM1, ERCC1, RAD51, and
      XRCC3) would predict disease-free survival (DFS), overall survival (OS), and
      toxicity in the INT0144 trial, which was designed to investigate different
      postoperative regimens of 5-fluorouracil (5-FU)-based chemoradiation (CRT) in
      locally advanced rectal cancers: Arm 1 consisted of bolus 5-FU followed by 5-FU
      protracted venous infusion (PVI) with radiotherapy; arm 2 was induction and
      concomitant PVI 5-FU with radiotherapy and arm 3 was induction and concomitant
      bolus 5-FU with radiotherapy. EXPERIMENTAL DESIGN: DNA from 746 stage II/III
      rectal patients enrolled in the Southwest Oncology Group (SWOG) S9304 phase III
      trial was analyzed. Genomic DNA was extracted from formalin-fixed, paraffin
      embedded (FFPE) tumor tissue. The polymorphisms were analyzed using direct DNA
      sequencing or polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP). RESULTS: GSTP1-Ile105Val (rs1695) was significantly associated with
      DFS and OS and its effect did not vary by treatment arm. The five-year DFS and OS
      were 53% and 58%, respectively, for G/G, 66% and 72% for G/A, and 57% and 66% for
      A/A patients. In arm 2, IL8-251A/A genotype (rs4073) was associated with a lower
      risk of toxicities (P = 0.04). The VEGFR2 H472Q Q/Q genotype (rs1870377) was
      associated with a higher risk of grade 3-5 proximal upper gastrointestinal tract
      (PUGIT) mucositis (P = 0.04) in arm 2. However, in arm 1, this genotype was
      associated with a lower risk of PUGIT mucositis (P = 0.004). CONCLUSION: rs1695
      may be prognostic in patients with rectal cancer treated with adjuvant CRT.
      rs4073 and rs1870377 may exhibit different associations with toxicity, according
      to the 5-FU schedule.

PMID- 25589621
TI  - Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic
      colorectal cancer patients.
AB  - PURPOSE: BRAF-mutant metastatic colorectal cancer (mCRC) forms an aggressive
      subset of colorectal cancer with minimal response to selective RAF inhibitors.
      Preclinical data show that reactivation of EGFR signaling occurs in colorectal
      tumor cells treated with RAF inhibitors and that the addition of an EGFR
      inhibitor enhances antitumor activity. These data suggest that combined therapy
      with RAF and EGFR inhibitors could be an effective strategy for treating BRAF
      V600E mCRC. EXPERIMENTAL DESIGN: We undertook a pilot trial to assess the
      response rate and safety of the BRAF inhibitor vemurafenib combined with anti
      EGFR antibody panitumumab in patients with BRAF-mutant mCRC. Patients received
      standard approved doses of panitumumab and vemurafenib. RESULTS: Fifteen patients
      were treated. Performance status was Eastern Cooperative Oncology Group (ECOG) 0
      in 4 patients (27%) and ECOG 1 in 11 patients (73%). All patients had progressed
      through at least one standard treatment regimen, and 8 (53%) had received
      previous fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy. Treatment
      was well tolerated, with less cutaneous toxicity than would be expected with
      either agent, and no cases of keratoacanthomas/squamous cell carcinomas. Tumor
      regressions were seen in 10 of 12 evaluable patients with partial responses in 2
      patients (100% and 64% regression lasting 40 and 24 weeks, respectively), and
      stable disease lasting over 6 months in 2 patients. CONCLUSIONS: Combined RAF and
      EGFR inhibition is well tolerated, with less cutaneous toxicity than would be
      expected with either agent, and results in modest clinical activity in this
      highly aggressive and chemoresistant subset of CRC.

PMID- 25589622
TI  - Gain of HIF-1alpha under normoxia in cancer mediates immune adaptation through
      the AKT/ERK and VEGFA axes.
AB  - PURPOSE: Adaptation to host immune surveillance is now recognized as a hallmark
      of cancer onset and progression, and represents an early, indispensable event in
      cancer evolution. This process of evolution is first instigated by an immune
      selection pressure imposed by natural host surveillance mechanisms and may then
      be propagated by vaccination or other types of immunotherapy. EXPERIMENTAL
      DESIGN: We developed a system to simulate cancer evolution in a live host and to
      dissect the mechanisms responsible for adaptation to immune selection. Here, we
      show that the oxygen-sensitive alpha subunit of hypoxia-inducible factor 1 (HIF
      1alpha) plays a central role in cancer immune adaptation under conditions of
      normal oxygen tension. RESULTS: We found that tumor cells gain HIF-1alpha in the
      course of immune selection under normoxia and that HIF-1alpha renders tumor cells
      resistant to lysis by tumor-specific cytotoxic T lymphocytes (CTL) in culture and
      in mice. The effects of HIF-1alpha on immune adaptation were mediated through
      VEGFA-dependent activation of the AKT and ERK signaling pathways, which induced
      an antiapoptotic gene expression network in tumor cells. CONCLUSIONS: Our study
      therefore establishes a link between immune selection, overexpression of HIF
      1alpha, and cancer immune adaptation under normoxia, providing new opportunities
      for molecular intervention in patients with cancer.

PMID- 25589623
TI  - KEAP1 Genetic Polymorphisms Associate with Breast Cancer Risk and Survival
      Outcomes.
AB  - PURPOSE: Defective oxidative stress response may increase cancer susceptibility.
      In tumors, these rescue mechanisms may cause chemo- and radioresistance impacting
      patient outcome. We previously showed that genetic variation in the nuclear
      factor erythroid 2-related factor 2 (NFE2L2) is associated with breast cancer
      risk and prognosis. Here we further studied this pathway by investigating Kelch
      like ECH-associated protein 1 (KEAP1). EXPERIMENTAL DESIGN: Five tagging SNPs in
      the KEAP1 gene were genotyped in 996 breast cancer cases and 880 controls from
      two Finnish case-control sets. KEAP1 protein expression was studied in 373
      invasive breast cancer tumors. RESULTS: rs34197572 genotype TT was associated
      with increased risk of breast cancer in the KBCP samples [P = 1.8*10(-4); OR,
      7.314; confidence interval (CI), 2.185-24.478]. rs11085735 allele A was
      associated with lower KEAP1 protein expression (P = 0.040; OR,= 3.545) and high
      nuclear NRF2 expression (P = 0.009; OR, 2.445) and worse survival in all invasive
      cases (P = 0.023; HR, 1.634). When including treatment data, rs11085735 was
      associated with recurrence-free survival (RFS; P = 0.020; HR, 1.545) and breast
      cancer-specific survival (P = 0.016; HR, 1.683) and rs34197572 with overall
      survival (P = 0.045; HR, 1.304). rs11085735 associated with RFS also among
      tamoxifen-treated cases (P = 0.003; HR, 3.517). Among radiotherapy-treated cases,
      overall survival was associated with rs34197572 (P = 0.018; HR, 1.486) and
      rs8113472 (P = 0.025; HR, 1.455). RFS was associated with rs9676881 (P = 0.024;
      HR, 1.452) and rs1048290 (P = 0.020; HR, 1.468) among all invasive cases and
      among estrogen receptor (ER)-positive tamoxifen-treated cases (P = 0.018; HR,
      2.407 and P = 0.015; HR, 2.476, respectively). CONCLUSIONS: The present findings
      suggest that the investigated SNPs have effects related to oxidative stress
      induced by cancer treatment, supporting involvement of the NRF2/KEAP1 pathway in
      breast cancer susceptibility and patient outcome.

PMID- 25589625
TI  - Antibody-mediated delivery of anti-KRAS-siRNA in vivo overcomes therapy
      resistance in colon cancer.
AB  - PURPOSE: KRAS mutations are frequent driver mutations in multiple cancers. KRAS
      mutations also induce anti-EGFR antibody resistance in adenocarcinoma such as
      colon cancer. The aim of this study was to overcome anti-EGFR antibody resistance
      by coupling the antibody to KRAS-specific siRNA. EXPERIMENTAL DESIGN: The anti
      EGFR antibody was chemically coupled to siRNA. The resulting complex was tested
      for antibody binding efficiency, serum stability and ability to deliver siRNA to
      EGFR-expressing cells. Western blotting, viability, apoptosis, and colony
      formation assays were performed for efficacy evaluation in vitro. Furthermore,
      therapeutic activity of the antibody-KRAS-siRNA complexes was examined in in vivo
      xenograft mouse tumor models. RESULTS: Antibody-siRNA complexes were targeted and
      internalized via the EGFR receptor. Upon internalization, target gene expression
      was strongly and specifically repressed, followed by a reduced proliferation and
      viability, and induced apoptosis of the cells in vitro. Clonogenic growth of
      mutant KRAS-bearing cells was suppressed by KRAS-siRNA-anti-EGFR antibody
      complexes. In xenograft mouse models, anti-EGFR antibody-KRAS-siRNA complexes
      significantly slowed tumor growth in anti-EGFR-resistant cells. CONCLUSIONS: The
      coupling of siRNA against KRAS to anti-EGFR antibodies provides a novel therapy
      approach for KRAS-mutated EGFR-positive cancer cells in vitro and in vivo. These
      findings provide an innovative approach for cancer-specific siRNA application and
      for enhanced therapeutic potential of monoclonal antibody therapy and
      personalized treatment of cancer entities.

PMID- 25589624
TI  - Randomized Trial of Oral Cyclophosphamide and Veliparib in High-Grade Serous
      Ovarian, Primary Peritoneal, or Fallopian Tube Cancers, or BRCA-Mutant Ovarian
      Cancer.
AB  - PURPOSE: Veliparib, a PARP inhibitor, demonstrated clinical activity in
      combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors
      in a phase I trial. To define the relative contribution of PARP inhibition to the
      observed clinical activity, we conducted a randomized phase II trial to determine
      the response rate of veliparib in combination with cyclophosphamide compared with
      cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or
      in patients with pretreated primary peritoneal, fallopian tube, or high-grade
      serous ovarian cancers (HGSOC). EXPERIMENTAL DESIGN: Adult patients were
      randomized to receive cyclophosphamide alone (50 mg orally once daily) or with
      veliparib (60 mg orally once daily) in 21-day cycles. Crossover to the
      combination was allowed at disease progression. RESULTS: Seventy-five patients
      were enrolled and 72 were evaluable for response; 38 received cyclophosphamide
      alone and 37 the combination as their initial treatment regimen. Treatment was
      well tolerated. One complete response was observed in each arm, with three
      partial responses (PR) in the combination arm and six PRs in the cyclophosphamide
      alone arm. Genetic sequence and expression analyses were performed for 211 genes
      involved in DNA repair; none of the detected genetic alterations were
      significantly associated with treatment benefit. CONCLUSION: This is the first
      trial that evaluated single-agent, low-dose cyclophosphamide in HGSOC,
      peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well
      tolerated and clinical activity was observed; the addition of veliparib at 60 mg
      daily did not improve either the response rate or the median progression-free
      survival.

PMID- 25589626
TI  - Clinical and biological effects of an agonist anti-CD40 antibody: a Cancer
      Research UK phase I study.
AB  - PURPOSE: This phase I study aimed to establish the biologic effects and MTD of
      the agonistic IgG1 chimeric anti-CD40 antibody ChiLob7/4 in patients (pts) with a
      range of CD40-expressing solid tumors and diffuse large B-cell lymphoma,
      resistant to conventional therapy. Potential mechanisms of action for agonistic
      anti-CD40 include direct cytotoxic effects on tumor cells and conditioning of
      antigen-presenting cells. EXPERIMENTAL DESIGN: ChiLob7/4 was given by IV infusion
      weekly for 4 doses at a range from 0.5 to 240 mg/dose. Validated ELISAs were used
      to quantify ChiLob7/4 in serum and test for anti-chimeric MAb (HACA) responses.
      Pharmacodynamic assessments included quantitation of T-cell, natural killer-cell,
      and B-cell numbers and activation in blood by flow cytometry and a panel of
      cytokines in plasma by Luminex technology. Planned dose escalation was in cohorts
      of 3 patients until MTD or biologic effect, defined as reduction of peripheral
      blood CD19(+) B cells to 10% or less of baseline. RESULTS: Twenty-nine courses of
      treatment were given to 28 subjects. The MTD was 200 mg * 4, with dose-limiting
      toxicity of liver transaminase elevations at 240 mg. At 200 mg (range between 2.1
      mg/kg and 3.3 mg/kg based on patient body weight), the trough level pretreatment
      was above 25 MUg/mL. Grade 1-2 infusion reactions were seen above the dose of 16
      mg, but could be prevented with single-dose corticosteroid premedication. HACA
      responses were seen after doses between 1.6 mg and 50 mg, but not above this.
      There were dose-dependent falls in blood B-cell numbers accompanied by reduced
      expression of CD21, and transient reductions in NK cell numbers with increased
      CD54 expression from 50 mg upward. MIP-1beta and IL12 plasma concentrations rose
      after doses above 16 mg. Fifteen of 29 treatments were accompanied by disease
      stabilization for a median 6 months, the longest for 37 months. CONCLUSIONS:
      ChiLob7/4 can activate B and NK cells at doses that can be administered safely,
      and should be tested in combination with other antibodies and chemotherapy
      agents.

PMID- 25589627
TI  - Identification of Biological Relevant Minor Histocompatibility Antigens within
      the B-lymphocyte-Derived HLA-Ligandome Using a Reverse Immunology Approach.
AB  - PURPOSE: T-cell recognition of minor histocompatibility antigens (MiHA) not only
      plays an important role in the beneficial graft-versus-leukemia (GVL) effect of
      allogeneic stem cell transplantation (allo-SCT) but also mediates serious GVH
      complications associated with allo-SCT. Using a reverse immunology approach, we
      aim to develop a method enabling the identification of T-cell responses directed
      against predefined antigens, with the goal to select those MiHAs that can be used
      clinically in combination with allo-SCT. EXPERIMENTAL DESIGN: In this study, we
      used a recently developed MiHA selection algorithm to select candidate MiHAs
      within the HLA-presented ligandome of transformed B cells. From the HLA-presented
      ligandome that predominantly consisted of monomorphic peptides, 25 polymorphic
      peptides with a clinically relevant allele frequency were selected. By high
      throughput screening, the availability of high-avidity T cells specific for these
      MiHA candidates in different healthy donors was analyzed. RESULTS: With the use
      of MHC multimer enrichment, analyses of expanded T cells by combinatorial coding
      MHC multimer flow cytometry, and subsequent single-cell cloning, positive T-cell
      clones directed to two new MiHA: LB-CLYBL-1Y and LB-TEP1-1S could be
      demonstrated, indicating the immunogenicity of these two MiHAs. CONCLUSIONS: The
      biologic relevance of MiHA LB-CLYBL-1Y was demonstrated by the detection of LB
      CLYBL-1Y-specific T cells in a patient suffering from acute myeloid leukemia
      (AML) that experienced an anti-leukemic response after treatment with allo-SCT.

PMID- 25589629
TI  - Tackling the achilles' heel of genetic testing.
AB  - Assigning pathogenicity to rare genetic variants is at its hardest with the
      enormous titin gene, but comprehensive genomic analysis makes the task more
      tractable (Roberts et al., this issue). 

PMID- 25589628
TI  - Cross-species antibody microarray interrogation identifies a 3-protein panel of
      plasma biomarkers for early diagnosis of pancreas cancer.
AB  - PURPOSE: Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of
      cancer-related death in the United States, and its incidence is on the rise.
      Advanced disease is nearly uniformly lethal, emphasizing the need to identify PDA
      at its earliest stages. To discover early biomarkers of PDA, we evaluated the
      circulating proteome in murine preinvasive and invasive plasma samples and human
      prediagnostic and diagnostic samples. EXPERIMENTAL DESIGN: Using a customized
      antibody microarray platform containing >4,000 features, we interrogated plasma
      samples spanning preinvasive and invasive disease from a highly faithful mouse
      model of PDA. In parallel, we mined prediagnostic plasma from women in the
      Women's Health Initiative (WHI) who would later succumb to PDA together with
      matched, cancer-free control samples. Samples collected after an establishing
      diagnosis of PDA were also interrogated to further validate markers. RESULTS: We
      identified ERBB2 and TNC in our cross-species analyses, and multiple antibodies
      identified ESR1 in prediagnostic plasma from people that succumb to PDA. This 3
      marker panel had an AUC of 0.86 (95% confidence interval [CI], 0.76-0.96) for the
      diagnostic cohort that increased to 0.97 (95% CI, 0.92-1.0) with CA19-9 included.
      The 3-marker panel also had an AUC of 0.68 (95% CI, 0.58-0.77) for the
      prediagnostic cohort. CONCLUSIONS: We identified potential disease detection
      markers in plasma up to 4 years before death from PDA with superior performance
      to CA19-9. These markers might be especially useful in high-risk cohorts to
      diagnose early, resectable disease, particularly in patients that do not produce
      CA19-9.

PMID- 25589631
TI  - The long-acting integrase inhibitor GSK744 protects macaques from repeated
      intravaginal SHIV challenge.
AB  - Daily preexposure prophylaxis (PrEP) with Truvada is a proven HIV prevention
      strategy; however, its effectiveness is limited by low adherence. Antiretroviral
      drug formulations that require infrequent dosing may increase adherence and thus
      PrEP effectiveness. We investigated whether monthly injections of a long-acting
      formulation of the HIV integrase inhibitor GSK1265744 (GSK744 LA) prevented
      simian/human immunodeficiency virus (SHIV) infection by vaginal challenge in
      macaques. Female pigtail macaques (n = 12) were exposed to intravaginal
      inoculations of SHIV twice a week for up to 11 weeks. Half of the animals
      received a GSK744 LA injection every 4 weeks, and half received placebo. GSK744
      LA, at plasma concentrations achievable with quarterly injections in humans,
      protected all six macaques from infection. Placebo controls were all infected
      after a median of 4 (range, 2 to 20) vaginal challenges with SHIV. Efficacy was
      related to high and sustained vaginal and plasma drug concentrations that
      remained above the protein-adjusted 90% inhibitory concentration during the
      dosing cycles. These data support advancement of GSK744 LA as a potential PrEP
      candidate for women. 

PMID- 25589630
TI  - A long-acting integrase inhibitor protects female macaques from repeated high
      dose intravaginal SHIV challenge.
AB  - Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV
      (simian immunodeficiency virus) integrase and was shown to be an effective
      preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human
      immunodeficiency virus) rhesus macaque challenge model. We examined the
      pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose
      intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera
      (depot medroxyprogesterone acetate), which promotes viral transmission vaginally.
      When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50
      mg/kg) monthly, systemic and tissue drug concentrations were lower than
      previously observed in male rhesus macaques. GSK744 concentrations were fivefold
      lower on average in cervical tissues than in rectal tissues. Eight female rhesus
      macaques were treated with GSK744 LA at week 0, and four female rhesus macaques
      served as controls. All animals received a high-dose challenge of SHIV162P3 at
      week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas
      viremia was detected 1 to 2 weeks after SHIV challenge in all control animals.
      The GSK744 LA-treated rhesus macaques were given a second administration of drug
      at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected
      six of eight female rhesus macaques against three high-dose SHIV challenges,
      whereas all control animals became infected after the first challenge (P =
      0.0003, log-rank test). These results support further clinical development of
      GSK744 LA for PrEP. 

PMID- 25589633
TI  - Atypical risk factor profile and excellent long-term outcomes of young patients
      treated with primary percutaneous coronary intervention for ST-elevation
      myocardial infarction.
AB  - INTRODUCTION: Several studies have examined the relationship between age and
      clinical outcomes in patients with ST-elevation myocardial infarction (STEMI)
      treated by primary percutaneous coronary intervention (PPCI). The majority of
      studies have concentrated on describing elderly patients and there has been less
      focus on the profile and outcome of young patients suffering from STEMI. The aim
      of this study was to describe the clinical profile and outcomes of young patients
      compared with an older cohort and to establish what risk factors were associated
      with young patients having PPCI for STEMI. METHODS: This was an observational
      cohort study of 3618 patients with STEMI treated by PPCI at a regional heart
      attack centre in London between January 2004 and September 2012. Clinical
      characteristics and outcomes in (young) patients aged <= 45 years were compared
      with those in (older) patients aged >45 years. The primary and main secondary
      outcomes were all-cause mortality and major adverse cardiovascular event rates,
      respectively, at a median follow-up of 3.0 (interquartile range 1.2-4.6) years.
      RESULTS: Of the 3618 patients, 367 (10.1%) were aged <= 45 years and 3251 (89.9%)
      were aged >45 years. The proportion of patients aged <= 45 years increased from
      8.5% to 11.5% (p=0.04) during the study period. Compared with older patients,
      those aged <= 45 years were more likely to be male, smokers, of South Asian
      ethnicity and to have a family history of premature coronary artery disease.
      Young patients were less likely to have a history of hypertension,
      hypercholesterolaemia, diabetes mellitus, previous myocardial infarction,
      myocardial revascularisation, or to have left ventricular systolic impairment or
      renal impairment. Over the follow-up period, mortality (2.7% vs. 7.6%; p<0.0001)
      and major adverse cardiovascular event rates (7.0% vs. 13.5%; p<0.0001) were
      significantly lower in patients aged <= 45 years compared with older patients.
      After adjustment for potential confounding factors, young age remained a
      predictor of reduced all cause mortality when compared with older patients
      (hazard ratio 0.12 (95% confidence interval 0.04-0.38)), including after
      incorporation of a propensity score (hazard ratio: 0.14 (95% confidence interval
      0.04-0.36)). CONCLUSIONS: In this cohort of patients with STEMI treated by PPCI
      there was an increasing incidence of young patients aged <= 45 years throughout
      the study period. These patients were more often male, smokers and of South Asian
      ethnicity. Outcomes in younger patients was good. Focusing preventative
      strategies on smokers and high risk ethnic groups may help reduce the incidence
      of premature coronary artery disease.

PMID- 25589634
TI  - A simple risk chart for initial risk assessment of 30-day mortality in patients
      with cardiogenic shock from ST-elevation myocardial infarction.
AB  - AIMS: Early risk stratification is important in patients with cardiogenic shock
      from ST-elevation myocardial infarction (STEMI). We aimed to develop a simple
      risk chart that includes clinical parameters that are readily available at time
      of hospital admission to assess risk of 30-day mortality. METHODS AND RESULTS: A
      series of 544 STEMI patients admitted to undergo primary percutaneous coronary
      intervention and presenting with cardiogenic shock were included between 2000 and
      2012. Overall 30-day mortality was 38.4% and did not change over the years (p
      trend=0.64). Baseline variables that were available at time of hospital admission
      were entered into a logistic regression model in a forward stepwise manner. Only
      age (odds ratio (OR) per year 1.05, 95% confidence interval (CI) 1.04-1.07,
      p<0.001), initial serum lactate level (OR per mmol/l 1.17, 95% CI 1.11-1.24,
      p<0.001) and initial creatinine level above the upper limit of normal (OR 2.89,
      95% CI 1.90-4.37, p<0.001) remained independent predictors, and were subsequently
      used to develop a risk chart that stratifies risk of 30-day mortality into
      categories ranging from 0-20% to 80-100%. The calibration plot showed a close
      relationship between expected and observed mortality. The risk chart had a higher
      discriminative accuracy than the GRACE score (c-index 0.75 vs. 0.66, p=0.009).
      Adding variables that were obtained from coronary angiography and during clinical
      course did not significantly improve discriminative accuracy of risk chart (c
      index 0.77, p=0.48). CONCLUSION: Mortality of patients with cardiogenic shock
      from STEMI undergoing primary percutaneous coronary intervention can be well
      predicted already at time of hospital admission by a risk chart that uses only
      three variables, namely, age, initial serum lactate and creatinine level.

PMID- 25589635
TI  - Antigenic relationships among porcine epidemic diarrhea virus and transmissible
      gastroenteritis virus strains.
AB  - Porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus
      (TGEV) are economically important swine enteropathogenic coronaviruses. These two
      viruses belong to two distinct species of the Alphacoronavirus genus within
      Coronaviridae and induce similar clinical signs and pathological lesions in
      newborn piglets, but they are presumed to be antigenically distinct. In the
      present study, two-way antigenic cross-reactivity examinations between the
      prototype PEDV CV777 strain, three distinct U.S. PEDV strains (the original
      highly virulent PC22A, S indel Iowa106, and S 197del PC177), and two
      representative U.S. TGEV strains (Miller and Purdue) were conducted by cell
      culture immunofluorescent (CCIF) and viral neutralization (VN) assays. None of
      the pig TGEV antisera neutralized PEDV and vice versa. One-way cross-reactions
      were observed by CCIF between TGEV Miller hyperimmune pig antisera and all PEDV
      strains. Enzyme-linked immunosorbent assays, immunoblotting using monoclonal
      antibodies and Escherichia coli-expressed recombinant PEDV and TGEV nucleocapsid
      (N) proteins, and sequence analysis suggested at least one epitope on the N
      terminal region of PEDV/TGEV N protein that contributed to this cross-reactivity.
      Biologically, PEDV strain CV777 induced greater cell fusion in Vero cells than
      did U.S. PEDV strains. Consistent with the reported genetic differences, the
      results of CCIF and VN assays also revealed higher antigenic variation between
      PEDV CV777 and U.S. strains. IMPORTANCE: Evidence of antigenic cross-reactivity
      between porcine enteric coronaviruses, PEDV and TGEV, in CCIF assays supports the
      idea that these two species are evolutionarily related, but they are distinct
      species defined by VN assays. Identification of PEDV- or TGEV-specific antigenic
      regions allows the development of more specific immunoassays for each virus.
      Antigenic and biologic variations between the prototype and current PEDV strains
      could explain, at least partially, the recurrence of PEDV epidemics. Information
      on the conserved antigenicity among PEDV strains is important for the development
      of PEDV vaccines to protect swine from current highly virulent PEDV infections.

PMID- 25589636
TI  - Mapping the Interactions between the NS4B and NS3 proteins of dengue virus.
AB  - Flavivirus RNA synthesis is mediated by a multiprotein complex associated with
      the endoplasmic reticulum membrane, named the replication complex (RC). Within
      the flavivirus RC, NS4B, an integral membrane protein with a role in virulence
      and regulation of the innate immune response, binds to the NS3 protease-helicase.
      NS4B modulates the RNA helicase activity of NS3, but the molecular details of
      their interaction remain elusive. Here, we used dengue virus (DENV) to map the
      determinants for the NS3-NS4B interaction. Coimmunoprecipitation and an in situ
      proximity ligation assay confirmed that NS3 colocalizes with NS4B in both DENV
      infected cells and cells coexpressing both proteins. Surface plasmon resonance
      demonstrated that subdomains 2 and 3 of the NS3 helicase region and the
      cytoplasmic loop of NS4B are required for binding. Using nuclear magnetic
      resonance (NMR), we found that the isolated cytoplasmic loop of NS4B is flexible,
      with a tendency to form a three-turn alpha-helix and two short beta-strands. Upon
      binding to the NS3 helicase, 12 amino acids within the cytoplasmic loop of NS4B
      exhibited line broadening, suggesting a participation in the interaction.
      Sequence alignment showed that 4 of these 12 residues are strictly conserved
      across different flaviviruses. Mutagenesis analysis showed that three (Q134,
      G140, and N144) of the four evolutionarily conserved NS4B residues are essential
      for DENV replication. The mapping of the NS3/NS4B-interacting regions described
      here can assist the design of inhibitors that disrupt their interface for
      antiviral therapy. IMPORTANCE: NS3 and NS4B are essential components of the
      flavivirus RC. Using DENV as a model, we mapped the interaction between the viral
      NS3 and NS4B proteins. The subdomains 2 and 3 of NS3 helicase as well as the
      cytoplasmic loop of NS4B are critical for the interaction. Functional analysis
      delineated residues within the NS4B cytoplasmic loop that are crucial for DENV
      replication. Our findings reveal molecular details of how flavivirus NS3 protein
      cooperates with NS4B within the RC. In addition, this study has established the
      rationale and assays to search for inhibitors disrupting the NS3-NS4B interaction
      for antiviral drug discovery.

PMID- 25589632
TI  - Integrated allelic, transcriptional, and phenomic dissection of the cardiac
      effects of titin truncations in health and disease.
AB  - The recent discovery of heterozygous human mutations that truncate full-length
      titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as
      a common cause of end-stage dilated cardiomyopathy (DCM) promises new prospects
      for improving heart failure management. However, realization of this opportunity
      has been hindered by the burden of TTN-truncating variants (TTNtv) in the general
      population and uncertainty about their consequences in health or disease. To
      elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac
      phenotyping in 5267 individuals across the spectrum of cardiac physiology and
      integrated these data with RNA and protein analyses of human heart tissues. We
      report diversity of TTN isoform expression in the heart, define the relative
      inclusion of TTN exons in different isoforms (using the TTN transcript
      annotations available at http://cardiodb.org/titin), and demonstrate that these
      data, coupled with the position of the TTNtv, provide a robust strategy to
      discriminate pathogenic from benign TTNtv. We show that TTNtv is the most common
      genetic cause of DCM in ambulant patients in the community, identify clinically
      important manifestations of TTNtv-positive DCM, and define the penetrance and
      outcomes of TTNtv in the general population. By integrating genetic,
      transcriptome, and protein analyses, we provide evidence for a length-dependent
      mechanism of disease. These data inform diagnostic criteria and management
      strategies for TTNtv-positive DCM patients and for TTNtv that are identified as
      incidental findings. 

PMID- 25589638
TI  - On the stability of parainfluenza virus 5 F proteins.
AB  - The crystal structure of the F protein (prefusion form) of the paramyxovirus
      parainfluenza virus 5 (PIV5) WR isolate was determined. We investigated the basis
      by which point mutations affect fusion in PIV5 isolates W3A and WR, which differ
      by two residues in the F ectodomain. The P22 stabilizing site acts through a
      local conformational change and a hydrophobic pocket interaction, whereas the
      S443 destabilizing site appears sensitive to both conformational effects and
      amino acid charge/polarity changes. 

PMID- 25589637
TI  - A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene.
AB  - Recombinant trimeric mimics of the human immunodeficiency virus type 1 (HIV-1)
      envelope glycoprotein (Env) spike should expose as many epitopes as possible for
      broadly neutralizing antibodies (bNAbs) but few, if any, for nonneutralizing
      antibodies (non-NAbs). Soluble, cleaved SOSIP.664 gp140 trimers based on the
      subtype A strain BG505 approach this ideal and are therefore plausible vaccine
      candidates. Here, we report on the production and in vitro properties of a new
      SOSIP.664 trimer derived from a subtype B env gene, B41, including how to make
      this protein in low-serum media without proteolytic damage (clipping) to the V3
      region. We also show that nonclipped trimers can be purified successfully via a
      positive-selection affinity column using the bNAb PGT145, which recognizes a
      quaternary structure-dependent epitope at the trimer apex. Negative-stain
      electron microscopy imaging shows that the purified, nonclipped, native-like B41
      SOSIP.664 trimers contain two subpopulations, which we propose represent an
      equilibrium between the fully closed and a more open conformation. The latter is
      different from the fully open, CD4 receptor-bound conformation and may represent
      an intermediate state of the trimer. This new subtype B trimer adds to the
      repertoire of native-like Env proteins that are suitable for immunogenicity and
      structural studies. IMPORTANCE: The cleaved, trimeric envelope protein complex is
      the only neutralizing antibody target on the HIV-1 surface. Many vaccine
      strategies are based on inducing neutralizing antibodies. For HIV-1, one approach
      involves using recombinant, soluble protein mimics of the native trimer. At
      present, the only reliable way to make native-like, soluble trimers in practical
      amounts is via the introduction of specific sequence changes that confer
      stability on the cleaved form of Env. The resulting proteins are known as
      SOSIP.664 gp140 trimers, and the current paradigm is based on the BG505 subtype A
      env gene. Here, we describe the production and characterization of a SOSIP.664
      protein derived from a subtype B gene (B41), together with a simple, one-step
      method to purify native-like trimers by affinity chromatography with a trimer
      specific bNAb, PGT145. The resulting trimers will be useful for structural and
      immunogenicity experiments aimed at devising ways to make an effective HIV-1
      vaccine.

PMID- 25589639
TI  - High preexisting serological antibody levels correlate with diversification of
      the influenza vaccine response.
AB  - Reactivation of memory B cells allows for a rapid and robust immune response upon
      challenge with the same antigen. Variant influenza virus strains generated
      through antigenic shift or drift are encountered multiple times over the lifetime
      of an individual. One might predict, then, that upon vaccination with the
      trivalent influenza vaccine across multiple years, the antibody response would
      become more and more dominant toward strains consistently present in the vaccine
      at the expense of more divergent strains. However, when we analyzed the vaccine
      induced plasmablast, memory, and serological responses to the trivalent influenza
      vaccine between 2006 and 2013, we found that the B cell response was most robust
      against more divergent strains. Overall, the antibody response was highest when
      one or more strains contained in the vaccine varied from year to year. This
      suggests that in the broader immunological context of viral antigen exposure, the
      B cell response to variant influenza virus strains is not dictated by the
      composition of the memory B cell precursor pool. The outcome is instead a
      diversified B cell response. IMPORTANCE: Vaccine strategies are being designed to
      boost broadly reactive B cells present in the memory repertoire to provide
      universal protection to the influenza virus. It is important to understand how
      past exposure to influenza virus strains affects the response to subsequent
      immunizations. The viral epitopes targeted by B cells responding to the vaccine
      may be a direct reflection of the B cell memory specificities abundant in the
      preexisting immune repertoire, or other factors may influence the vaccine
      response. Here, we demonstrate that high preexisting serological antibody levels
      to a given influenza virus strain correlate with low production of antibody
      secreting cells and memory B cells recognizing that strain upon revaccination. In
      contrast, introduction of antigenically novel strains generates a robust B cell
      response. Thus, both the preexisting memory B cell repertoire and serological
      antibody levels must be taken into consideration in predicting the quality of the
      B cell response to new prime-boost vaccine strategies.

PMID- 25589640
TI  - Absence of the uracil DNA glycosylase of murine gammaherpesvirus 68 impairs
      replication and delays the establishment of latency in vivo.
AB  - Uracil DNA glycosylases (UNG) are highly conserved proteins that preserve DNA
      fidelity by catalyzing the removal of mutagenic uracils. All herpesviruses encode
      a viral UNG (vUNG), and yet the role of the vUNG in a pathogenic course of
      gammaherpesvirus infection is not known. First, we demonstrated that the vUNG of
      murine gammaherpesvirus 68 (MHV68) retains the enzymatic function of host UNG in
      an in vitro class switch recombination assay. Next, we generated a recombinant
      MHV68 with a stop codon in ORF46/UNG (DeltaUNG) that led to loss of UNG activity
      in infected cells and a replication defect in primary fibroblasts. Acute
      replication of MHV68DeltaUNG in the lungs of infected mice was reduced 100-fold
      and was accompanied by a substantial delay in the establishment of splenic
      latency. Latency was largely, yet not fully, restored by an increase in virus
      inoculum or by altering the route of infection. MHV68 reactivation from latent
      splenocytes was not altered in the absence of the vUNG. A survey of host UNG
      activity in cells and tissues targeted by MHV68 indicated that the lung tissue
      has a lower level of enzymatic UNG activity than the spleen. Taken together,
      these results indicate that the vUNG plays a critical role in the replication of
      MHV68 in tissues with limited host UNG activity and this vUNG-dependent
      expansion, in turn, influences the kinetics of latency establishment in distal
      reservoirs. IMPORTANCE: Herpesviruses establish chronic lifelong infections using
      a strategy of replicative expansion, dissemination to latent reservoirs, and
      subsequent reactivation for transmission and spread. We examined the role of the
      viral uracil DNA glycosylase, a protein conserved among all herpesviruses, in
      replication and latency of murine gammaherpesvirus 68. We report that the viral
      UNG of this murine pathogen retains catalytic activity and influences replication
      in culture. The viral UNG was impaired for productive replication in the lung.
      This defect in expansion at the initial site of acute replication was associated
      with a substantial delay of latency establishment in the spleen. The levels of
      host UNG were substantially lower in the lung compared to the spleen, suggesting
      that herpesviruses encode a viral UNG to compensate for reduced host enzyme
      levels in some cell types and tissues. These data suggest that intervention at
      the site of initial replicative expansion can delay the establishment of latency,
      a hallmark of chronic herpesvirus infection.

PMID- 25589641
TI  - Constitutive but not inducible attenuation of transforming growth factor beta
      signaling increases natural killer cell responses without directly affecting
      dendritic cells early after persistent viral infection.
AB  - Rapid innate responses to viral encounters are crucial to shaping the outcome of
      infection, from viral clearance to persistence. Transforming growth factor beta
      (TGF-beta) is a potent immune suppressor that is upregulated early upon viral
      infection and maintained during chronic infections in both mice and humans.
      However, the role of TGF-beta signaling in regulating individual cell types in
      vivo is still unclear. Using infections with two different persistent viruses,
      murine cytomegalovirus (MCMV) and lymphocytic choriomeningitis virus (LCMV;
      Cl13), in their natural rodent host, we observed that TGF-beta signaling on
      dendritic cells (DCs) did not dampen DC maturation or cytokine production in the
      early stages of chronic infection with either virus in vivo. In contrast, TGF
      beta signaling prior to (but not during) chronic viral infection directly
      restricted the natural killer (NK) cell number and effector function. This
      restriction likely compromised both the early control of and host survival upon
      MCMV infection but not the long-term control of LCMV infection. These data
      highlight the context and timing of TGF-beta signaling on different innate cells
      that contribute to the early host response, which ultimately influences the
      outcome of chronic viral infection in vivo. IMPORTANCE: In vivo host responses to
      pathogens are complex processes involving the cooperation of many different
      immune cells migrating to specific tissues over time, but these events cannot be
      replicated in vitro. Viruses causing chronic infections are able to subvert this
      immune response and represent a human health burden. Here we used two well
      characterized viruses that are able to persist in their natural mouse host to
      dissect the role of the suppressive molecule TGF-beta in dampening host responses
      to infection in vivo. This report presents information that allows an increased
      understanding of long-studied TGF-beta signaling by examining its direct effect
      on different immune cells that are activated very early after in vivo viral
      infection and may aid with the development of new antiviral therapeutic
      strategies.

PMID- 25589642
TI  - Overlapping local and long-range RNA-RNA interactions modulate dengue virus
      genome cyclization and replication.
AB  - The dengue virus genome is a dynamic molecule that adopts different conformations
      in the infected cell. Here, using RNA folding predictions, chemical probing
      analysis, RNA binding assays, and functional studies, we identified new cis
      acting elements present in the capsid coding sequence that facilitate cyclization
      of the viral RNA by hybridization with a sequence involved in a local dumbbell
      structure at the viral 3' untranslated region (UTR). The identified interaction
      differentially enhances viral replication in mosquito and mammalian cells. 

PMID- 25589643
TI  - The aberrant gene-end transcription signal of the matrix M gene of human
      parainfluenza virus type 3 downregulates fusion F protein expression and the F
      specific antibody response in vivo.
AB  - Human parainfluenza virus type 3 (HPIV3), a paramyxovirus, is a major viral cause
      of severe lower respiratory tract disease in infants and children. The gene-end
      (GE) transcription signal of the HPIV3 matrix (M) protein gene is identical to
      those of the nucleoprotein and phosphoprotein genes except that it contains an
      apparent 8-nucleotide insert. This was associated with an increased synthesis of
      a readthrough transcript of the M gene and the downstream fusion (F) protein
      gene. We hypothesized that this insert may function to downregulate the
      expression of F protein by interfering with termination/reinitiation at the M-F
      gene junction, thus promoting the production of M-F readthrough mRNA at the
      expense of monocistronic F mRNA. To test this hypothesis, two similar recombinant
      HPIV3 viruses from which this insert in the M-GE signal was removed were
      generated. The M-GE mutants exhibited a reduction in M-F readthrough mRNA and an
      increase in monocistronic F mRNA. This resulted in a substantial increase in F
      protein synthesis in infected cells as well as enhanced incorporation of F
      protein into virions. The efficiency of mutant virus replication was similar to
      that of wild-type (wt) HPIV3 both in vitro and in vivo. However, the F-protein
      specific serum antibody response in hamsters was increased for the mutants
      compared to wt HPIV3. This study identifies a previously undescribed viral
      mechanism for attenuating the host adaptive immune response. Repairing the M-GE
      signal should provide a means to increase the antibody response to a live
      attenuated HPIV3 vaccine without affecting viral replication and attenuation.
      IMPORTANCE: The HPIV3 M-GE signal was previously shown to contain an apparent 8
      nucleotide insert that was associated with increased synthesis of a readthrough
      mRNA of the M gene and the downstream F gene. However, whether this had any
      significant effect on the synthesis of monocistronic F mRNA or F protein, virus
      replication, virion morphogenesis, and immunogenicity was unknown. Here, we show
      that the removal of this insert shifts F gene transcription from readthrough M-F
      mRNA to monocistronic F mRNA. This resulted in a substantial increase in the
      amount of F protein expressed in the cell and packaged in the virus particle.
      This did not affect virus replication but increased the F-specific antibody
      response in hamsters. Thus, in wild-type HPIV3, the aberrant M-GE signal operates
      a previously undescribed mechanism that reduces the expression of a major
      neutralization and protective antigen, resulting in reduced immunogenicity. This
      has implications for the design of live attenuated HPIV3 vaccines; specifically,
      the antibody response against F can be elevated by "repairing" the M-GE signal to
      achieve higher-level F antigen expression, with no effect on attenuation.

PMID- 25589644
TI  - Hepatitis C virus-mediated enhancement of microRNA miR-373 impairs the JAK/STAT
      signaling pathway.
AB  - Hepatitis C virus (HCV) is a serious global health problem and establishes
      chronic infection in a significant number of infected humans worldwide.
      Interferon (IFN) and IFN-stimulated genes (ISGs) are amplified during HCV
      infection but fail to eliminate virus from the liver in a large number of
      infected patients, and the mechanism is not fully understood. MicroRNAs (miRNAs)
      have been implicated in the control of many biological processes, including IFN
      signaling. To gain more insights into the role of cellular miRNAs in possible
      countermeasures of HCV for suppression of the host antiviral response, a miRNA
      array was performed by using primary human hepatocytes infected with in vitro
      cell culture-grown HCV. A group of miRNAs were modulated in HCV-infected primary
      human hepatocytes. We focused on miR-373, as this miRNA was significantly
      upregulated in HCV-infected primary human hepatocytes. Here, we analyzed the
      function of miR-373 in the context of HCV infection. HCV infection upregulates
      miR-373 expression in hepatocytes and HCV-infected liver biopsy specimens.
      Furthermore, we discovered that miR-373 directly targets Janus kinase 1 (JAK1)
      and IFN-regulating factor 9 (IRF9), important factors in the IFN signaling
      pathway. The upregulation of miR-373 by HCV also inhibited STAT1 phosphorylation,
      which is involved in ISG factor 3 (ISGF3) complex formation and ISG expression.
      The knockdown of miR-373 in hepatocytes enhanced JAK1 and IRF9 expression and
      reduced HCV RNA replication. Taken together, our results demonstrated that miR
      373 is upregulated during HCV infection and negatively regulated the type I IFN
      signaling pathway by suppressing JAK1 and IRF9. Our results offer a potential
      therapeutic approach for antiviral intervention. IMPORTANCE: Chronic HCV
      infection is one of the major causes of end-stage liver disease worldwide.
      Although the recent introduction of direct-acting antiviral (DAA) therapy is
      extremely encouraging, some infected individuals do not respond to this therapy.
      Furthermore, these drugs target HCV nonstructural proteins, and with selective
      pressure, the virus may develop a resistant strain. Therefore, understanding the
      impairment of IFN signals will help in designing additional therapeutic
      modalities. In this study, we provide evidence of HCV-mediated upregulation of
      miR-373 and show that miR-373 impairs IFN signaling by targeting JAK1/IRF9
      molecules. The knockdown of miR-373 inhibited HCV replication by upregulating
      interferon-stimulating gene expression. Together, these results provided new
      mechanistic insights into the role of miR-373 in HCV infection and suggest a new
      potential target against HCV infection.

PMID- 25589645
TI  - Long-term control of simian immunodeficiency virus (SIV) in cynomolgus macaques
      not associated with efficient SIV-specific CD8+ T-cell responses.
AB  - The spontaneous control of human and simian immunodeficiency viruses (HIV/SIV) is
      typically associated with specific major histocompatibility complex (MHC) class I
      alleles and efficient CD8(+) T-cell responses, but many controllers maintain
      viral control despite a nonprotective MHC background and weak CD8(+) T-cell
      responses. Therefore, the contribution of this response to maintaining long-term
      viral control remains unclear. To address this question, we transiently depleted
      CD8(+) T cells from five SIV-infected cynomolgus macaques with long-term viral
      control and weak CD8(+) T-cell responses. Among them, only one carried the
      protective MHC allele H6. After depletion, four of five controllers experienced a
      transient rebound of viremia. The return to undetectable viremia was accompanied
      by only modest expansion of SIV-specific CD8(+) T cells that lacked efficient SIV
      suppression capacity ex vivo. In contrast, the depletion was associated with
      homeostatic activation/expansion of CD4(+) T cells that correlated with viral
      rebound. In one macaque, viremia remained undetectable despite efficient CD8(+)
      cell depletion and inducible SIV replication from its CD4(+) T cells in vitro.
      Altogether, our results suggest that CD8(+) T cells are not unique contributors
      to the long-term maintenance of low viremia in this SIV controller model and that
      other mechanisms, such as weak viral reservoirs or control of activation, may be
      important players in control. IMPORTANCE: Spontaneous control of HIV-1 to
      undetectable levels is associated with efficient anti-HIV CD8(+) T-cell
      responses. However, in some cases, this response fades over time, although viral
      control is maintained, and many HIV controllers (weak responders) have very low
      frequencies of HIV-specific CD8(+) T cells. In these cases, the importance of CD8
      T cells in the maintenance of HIV-1 control is questionable. We developed a
      nonhuman primate model of durable SIV control with an immune profile resembling
      that of weak responders. Transient depletion of CD8(+) cells induced a rise in
      the viral load. However, viremia was correlated with CD4(+) T-cell activation
      subsequent to CD8(+) cell depletion. Regain of viral control to predepletion
      levels was not associated with restoration of the anti-SIV capacities of CD8(+) T
      cells. Our results suggest that CD8(+) T cells may not be involved in maintenance
      of viral control in weak responders and highlight the fact that additional
      mechanisms should not be underestimated.

PMID- 25589646
TI  - Sp1 sites in the noncoding control region of BK polyomavirus are key regulators
      of bidirectional viral early and late gene expression.
AB  - In kidney transplant patients with BK polyomavirus (BKPyV) nephropathy, viral
      variants arise bearing rearranged noncoding control regions (rr-NCCRs) that
      increase viral early gene expression, replicative fitness, and cytopathology. rr
      NCCRs result from various deletions and duplications of archetype NCCR (ww-NCCR)
      sequences, which alter transcription factor binding sites (TFBS). However, the
      role of specific TFBS is unclear. We inactivated 28 TFBS in the archetype NCCR by
      selective point mutations and examined viral gene expression in bidirectional
      reporter constructs. Compared to the archetype, group 1 mutations increased viral
      early gene expression similar to rr-NCCR and resulted from inactivating one Sp1
      or one Ets1 TFBS near the late transcription start site (TSS). Group 2 mutations
      conferred intermediate early gene activation and affected NF1, YY1, and p53 sites
      between early and late TSS. Group 3 mutations decreased early and late gene
      expression and included two other Sp1 sites near the early TSS. Recombinant
      viruses bearing group 1 NCCRs showed increased replication in human renal
      epithelial cells similar to clinical rr-NCCR variants. Group 2 and 3 viruses
      showed intermediate or no replication, respectively. A literature search revealed
      unnoticed group 1 mutations in BKPyV nephropathy, hemorrhagic cystitis, and
      disseminated disease. IMPORTANCE: The NCCRs of polyomaviruses mediate silent
      persistence of the viral genome as well as the appropriately timed (re)activation
      of the viral life cycle. This study indicates that the basal BKPyV NCCR is
      critically controlled by a hierarchy of single TFBS in the archetype NCCR that
      direct, modulate, and execute the bidirectional early and late viral gene
      expression. The results provide new insights into how BKPyV NCCR functions as a
      viral sensor of host cell signals and shed new light on how transcription factors
      like Sp1 control bidirectional viral gene expression and contribute to
      replication and pathology.

PMID- 25589647
TI  - Requirement for Fc effector mechanisms in the APOBEC3/Rfv3-dependent neutralizing
      antibody response.
AB  - Antiretroviral neutralizing antibody (NAb) responses are often evaluated in the
      absence of Fc-dependent immune effectors. In murine Friend retrovirus infection,
      Apobec3/Rfv3 promotes a potent polyclonal NAb response. Here, we show that the
      Apobec3/Rfv3-dependent NAb response correlated with virus-specific IgG2 titers
      and that the in vivo neutralization potency of Apobec3/Rfv3-resistant antisera
      was dependent on activating Fcgamma receptors but not complement. The data
      strengthen retroviral vaccine strategies aimed at eliciting NAbs that activate
      specific Fcgamma receptors. 

PMID- 25589648
TI  - Postchallenge administration of brincidofovir protects healthy and immune
      deficient mice reconstituted with limited numbers of T cells from lethal
      challenge with IHD-J-Luc vaccinia virus.
AB  - Protection from lethality by postchallenge administration of brincidofovir (BCV,
      CMX001) was studied in normal and immune-deficient (nude, nu/nu) BALB/c mice
      infected with vaccinia virus (VACV). Whole-body bioluminescence imaging was used
      to record total fluxes in the nasal cavity, lungs, spleen, and liver and to
      enumerate pox lesions on tails of mice infected via the intranasal route with
      10(5) PFU of recombinant IHD-J-Luc VACV expressing luciferase. Areas under the
      flux curve (AUCs) were calculated for individual mice to assess viral loads. A
      three-dose regimen of 20 mg/kg BCV administered every 48 h starting either on day
      1 or day 2 postchallenge protected 100% of mice. Initiating BCV treatment earlier
      was more efficient in reducing viral loads and in providing protection from pox
      lesion development. All BCV-treated mice that survived challenge were also
      protected from rechallenge with IHD-J-Luc or WRvFire VACV without additional
      treatment. In immune-deficient mice, BCV protected animals from lethality and
      reduced viral loads while animals were on the drug. Viral recrudescence occurred
      within 4 to 9 days, and mice succumbed ~10 to 20 days after treatment
      termination. Nude mice reconstituted with 10(5) T cells prior to challenge with
      10(4) PFU of IHD-J-Luc and treated with BCV postchallenge survived the infection,
      cleared the virus from all organs, and survived rechallenge with 10(5) PFU of IHD
      J-Luc VACV without additional BCV treatment. Together, these data suggest that
      BCV protects immunocompetent and partially T cell-reconstituted immune-deficient
      mice from lethality, reduces viral dissemination in organs, prevents pox lesion
      development, and permits generation of VACV-specific memory. IMPORTANCE: Mass
      vaccination is the primary element of the public health response to a smallpox
      outbreak. In addition to vaccination, however, antiviral drugs are required for
      individuals with uncertain exposure status to smallpox or for whom vaccination is
      contraindicated. Whole-body bioluminescence imaging was used to study the effect
      of brincidofovir (BCV) in normal and immune-deficient (nu/nu) mice infected with
      vaccinia virus, a model of smallpox. Postchallenge administration of 20 mg/kg BCV
      rescued normal and immune-deficient mice partially reconstituted with T cells
      from lethality and significantly reduced viral loads in organs. All BCV-treated
      mice that survived infection were protected from rechallenge without additional
      treatment. In immune-deficient mice, BCV extended survival. The data show that
      BCV controls viral replication at the site of challenge and reduces viral
      dissemination to internal organs, thus providing a shield for the developing
      adaptive immunity that clears the host of virus and builds virus-specific
      immunological memory.

PMID- 25589649
TI  - Relationships among dissemination of primary parainfluenza virus infection in the
      respiratory tract, mucosal and peripheral immune responses, and protection from
      reinfection: a noninvasive bioluminescence-imaging study.
AB  - Respiratory paramyxoviruses such as respiratory syncytial virus (RSV) and human
      parainfluenza virus type 1 (HPIV1) to HPIV4 infect virtually all children by the
      age of 2 to 5 years, leading to partial but incomplete protection from
      reinfection. Here, we used luciferase-expressing reporter Sendai viruses (the
      murine counterpart of HPIV1) to noninvasively measure primary infection, immune
      responses, and protection from reinfection by either a lethal challenge or
      natural transmission in living mice. Both nonattenuated and attenuated reporter
      Sendai viruses were used, and three inoculation strategies were employed:
      intramuscular (i.m.), intranasal (i.n.) at a low dose and low volume, and i.n. at
      a high dose and high volume. High-dose, high-volume i.n. inoculation resulted in
      the highest levels of antibody responses and protection from reinfection. Low
      dose, low-volume i.n. inoculation afforded complete protection from contact
      transmission and protection from morbidity, mortality, and viral growth during
      lethal challenge. i.m. inoculation was inferior to i.n. inoculation at inducing
      antibody responses and protection from challenge. For individual mice and across
      groups, the levels of serum binding and neutralizing antibody responses
      correlated with primary infection and protection from reinfection in the lungs.
      Contact transmission, the predominant mode of parainfluenza virus transmission,
      was modeled accurately by direct i.n. inoculation of Sendai virus at a low dose
      and low volume and was completely preventable by i.n. vaccination of an
      attenuated virus at a low dose and low volume. The data highlight differences in
      infection and protection from challenge in the upper versus lower respiratory
      tract and bear upon live attenuated vaccine development. IMPORTANCE: There are
      currently no licensed vaccines against HPIVs and human RSV (HRSV), important
      respiratory pathogens of infants and children. Natural infection leads to partial
      but incomplete protective immunity, resulting in subsequent reinfections even in
      the absence of antigenic drift. Here, we used noninvasive bioluminescence imaging
      in a mouse model to dissect relationships among (i) the mode of inoculation, (ii)
      the dynamics of primary infection, (iii) consequent immune responses, and (iv)
      protection from high-dose, high-volume lethal challenge and contact transmission,
      which we find here to be similar to that of a mild low-dose, low-volume upper
      respiratory tract (URT)-biased infection. Our studies demonstrate the superiority
      of i.n. versus i.m. vaccination in protection against both lethal challenge and
      contact transmission. In addition to providing correlates of protection that will
      assist respiratory virus vaccine development, these studies extend the
      development of an increasingly used technique for the study of viral infection
      and immunity, noninvasive bioluminescence imaging.

PMID- 25589651
TI  - Immune screening identifies novel T cell targets encoded by antisense reading
      frames of HIV-1.
AB  - Cytotoxic-T lymphocyte (CTL) responses to epitopes in alternative HIV reading
      frames have been reported. However, the extent of CTL responses to putative
      proteins encoded in antisense reading frames is unknown. Using sequence
      alignments and computational approaches, we here predict five potential antisense
      HIV proteins and characterize common CTL responses against them. Results suggest
      that antisense-derived sequences are commonly transcribed and translated and
      could encode functional proteins that contain important targets of anti-HIV
      cellular immunity. 

PMID- 25589650
TI  - Effective lethal mutagenesis of influenza virus by three nucleoside analogs.
AB  - Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high
      mutation rate and low mutational tolerance of many RNA viruses. This approach
      uses mutagenic drugs to increase viral mutation rates and burden viral
      populations with mutations that reduce the number of infectious progeny. We
      investigated the effectiveness of lethal mutagenesis as a strategy against
      influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5
      fluorouracil. All three drugs were active against a panel of seasonal H3N2 and
      laboratory-adapted H1N1 strains. We found that each drug increased the frequency
      of mutations in influenza virus populations and decreased the virus' specific
      infectivity, indicating a mutagenic mode of action. We were able to drive viral
      populations to extinction by passaging influenza virus in the presence of each
      drug, indicating that complete lethal mutagenesis of influenza virus populations
      can be achieved when a sufficient mutational burden is applied. Population-wide
      resistance to these mutagenic agents did not arise after serial passage of
      influenza virus populations in sublethal concentrations of drug. Sequencing of
      these drug-passaged viral populations revealed genome-wide accumulation of
      mutations at low frequency. The replicative capacity of drug-passaged populations
      was reduced at higher multiplicities of infection, suggesting the presence of
      defective interfering particles and a possible barrier to the evolution of
      resistance. Together, our data suggest that lethal mutagenesis may be a
      particularly effective therapeutic approach with a high genetic barrier to
      resistance for influenza virus. IMPORTANCE: Influenza virus is an RNA virus that
      causes significant morbidity and mortality during annual epidemics. Novel
      therapies for RNA viruses are needed due to the ease with which these viruses
      evolve resistance to existing therapeutics. Lethal mutagenesis is a broad
      spectrum strategy that exploits the high mutation rate and the low mutational
      tolerance of most RNA viruses. It is thought to possess a higher barrier to
      resistance than conventional antiviral strategies. We investigated the
      effectiveness of lethal mutagenesis against influenza virus using three different
      drugs. We showed that influenza virus was sensitive to lethal mutagenesis by
      demonstrating that all three drugs induced mutations and led to an increase in
      the generation of defective viral particles. We also found that it may be
      difficult for resistance to these drugs to arise at a population-wide level. Our
      data suggest that lethal mutagenesis may be an attractive anti-influenza strategy
      that warrants further investigation.

PMID- 25589652
TI  - Development of live-attenuated arenavirus vaccines based on codon deoptimization.
AB  - Arenaviruses have a significant impact on public health and pose a credible
      biodefense threat, but the development of safe and effective arenavirus vaccines
      has remained elusive, and currently, no Food and Drug Administration (FDA)
      licensed arenavirus vaccines are available. Here, we explored the use of a codon
      deoptimization (CD)-based approach as a novel strategy to develop live-attenuated
      arenavirus vaccines. We recoded the nucleoprotein (NP) of the prototypic
      arenavirus lymphocytic choriomeningitis virus (LCMV) with the least frequently
      used codons in mammalian cells, which caused lower LCMV NP expression levels in
      transfected cells that correlated with decreased NP activity in cell-based
      functional assays. We used reverse-genetics approaches to rescue a battery of
      recombinant LCMVs (rLCMVs) encoding CD NPs (rLCMV/NP(CD)) that showed attenuated
      growth kinetics in vitro. Moreover, experiments using the well-characterized
      mouse model of LCMV infection revealed that rLCMV/NP(CD1) and rLCMV/NP(CD2) were
      highly attenuated in vivo but, upon a single immunization, conferred complete
      protection against a subsequent lethal challenge with wild-type (WT) recombinant
      LCMV (rLCMV/WT). Both rLCMV/NP(CD1) and rLCMV/NP(CD2) were genetically and
      phenotypically stable during serial passages in FDA vaccine-approved Vero cells.
      These results provide proof of concept of the safety, efficacy, and stability of
      a CD-based approach for developing live-attenuated vaccine candidates against
      human-pathogenic arenaviruses. IMPORTANCE: Several arenaviruses cause severe
      hemorrhagic fever in humans and pose a credible bioterrorism threat. Currently,
      no FDA-licensed vaccines are available to combat arenavirus infections, while
      antiarenaviral therapy is limited to the off-label use of ribavirin, which is
      only partially effective and is associated with side effects. Here, we describe
      the generation of recombinant versions of the prototypic arenavirus LCMV encoding
      codon-deoptimized viral nucleoproteins (rLCMV/NP(CD)). We identified
      rLCMV/NP(CD1) and rLCMV/NP(CD2) to be highly attenuated in vivo but able to
      confer protection against a subsequent lethal challenge with wild-type LCMV.
      These viruses displayed an attenuated phenotype during serial amplification
      passages in cultured cells. Our findings support the use of this approach for the
      development of safe, stable, and protective live-attenuated arenavirus vaccines.

PMID- 25589654
TI  - Demographics of natural oral infection of mosquitos by Venezuelan equine
      encephalitis virus.
AB  - The within-host diversity of virus populations can be drastically limited during
      between-host transmission, with primary infection of hosts representing a major
      constraint to diversity maintenance. However, there is an extreme paucity of
      quantitative data on the demographic changes experienced by virus populations
      during primary infection. Here, the multiplicity of cellular infection (MOI) and
      population bottlenecks were quantified during primary mosquito infection by
      Venezuelan equine encephalitis virus, an arbovirus causing neurological disease
      in humans and equids. 

PMID- 25589653
TI  - Viral semaphorin inhibits dendritic cell phagocytosis and migration but is not
      essential for gammaherpesvirus-induced lymphoproliferation in malignant catarrhal
      fever.
AB  - Viral semaphorins are semaphorin 7A (sema7A) mimics found in pox- and
      herpesviruses. Among herpesviruses, semaphorins are encoded by gammaherpesviruses
      of the Macavirus genus only. Alcelaphine herpesvirus 1 (AlHV-1) is a macavirus
      that persistently infects wildebeest asymptomatically but induces malignant
      catarrhal fever (MCF) when transmitted to several species of susceptible
      ruminants and the rabbit model. MCF is caused by the activation/proliferation of
      latently infected T lymphocytes. Viral semaphorins have been suggested to mediate
      immune evasion mechanisms and/or directly alter host T cell function. We studied
      AlHV-sema, the viral semaphorin encoded by the A3 gene of AlHV-1. Phylogenetic
      analyses revealed independent acquisition of pox- and herpesvirus semaphorins,
      suggesting that these proteins might have distinct functions. AlHV-sema showed a
      predicted three-dimensional structure very similar to sema7A and conserved key
      residues in sema7A-plexinC1 interaction. Expression analyses revealed that AlHV
      sema is a secreted 93-kDa glycoprotein expressed during the early phase of virus
      replication. Purified AlHV-sema was able to bind to fibroblasts and dendritic
      cells and induce F-actin condensation and cell retraction through a plexinC1 and
      Rho/cofilin-dependent mechanism. Cytoskeleton rearrangement was further
      associated with inhibition of phagocytosis by dendritic cells and migration to
      the draining lymph node. Next, we generated recombinant viruses and demonstrated
      that the lack of A3 did not significantly affect virus growth in vitro and did
      not impair MCF induction and associated lymphoproliferative lesions. In
      conclusion, AlHV-sema has immune evasion functions through mechanisms similar to
      poxvirus semaphorin but is not directly involved in host T cell activation during
      MCF. IMPORTANCE: Whereas most poxviruses encode viral semaphorins, semaphorin
      like genes have only been identified in few gammaherpesviruses belonging to the
      Macavirus genus. Alcelaphine herpesvirus 1 (AlHV-1) is a macavirus carried
      asymptomatically by wildebeest but induces a latency-associated
      lymphoproliferative disease of T lymphocytes in various ruminant species, namely,
      malignant catarrhal fever (MCF). Viral semaphorins have been hypothesized to have
      immune evasion functions and/or be involved in activating latently infected T
      cells. We present evidence that the viral semaphorin AlHV-sema inhibits dendritic
      cell phagocytosis and migration to the draining lymph node, both being
      indispensable mechanisms for protective antiviral responses. Next, we engineered
      recombinant viruses unable to express AlHV-sema and demonstrated that this
      protein is dispensable for the induction of MCF. In conclusion, this study
      suggests that herpesvirus and poxvirus semaphorins have independently evolved
      similar functions to thwart the immune system of the host while AlHV-sema is not
      directly involved in MCF-associated T-cell activation.

PMID- 25589655
TI  - Broadly neutralizing anti-influenza virus antibodies: enhancement of neutralizing
      potency in polyclonal mixtures and IgA backbones.
AB  - Current influenza virus vaccines rely upon the accurate prediction of circulating
      virus strains months in advance of the actual influenza season in order to allow
      time for vaccine manufacture. Unfortunately, mismatches occur frequently, and
      even when perfect matches are achieved, suboptimal vaccine efficacy leaves
      several high-risk populations vulnerable to infection. However, the recent
      discovery of broadly neutralizing antibodies that target the hemagglutinin (HA)
      stalk domain has renewed hope that the development of "universal" influenza virus
      vaccines may be within reach. Here, we examine the functions of influenza A virus
      hemagglutinin stalk-binding antibodies in an endogenous setting, i.e., as
      polyclonal preparations isolated from human sera. Relative to monoclonal
      antibodies that bind to the HA head domain, the neutralization potency of
      monoclonal stalk-binding antibodies was vastly inferior in vitro but was enhanced
      by several orders of magnitude in the polyclonal context. Furthermore, we
      demonstrated a surprising enhancement in IgA-mediated HA stalk neutralization
      relative to that achieved by antibodies of IgG isotypes. Mechanistically, this
      could be explained in two ways. Identical variable regions consistently
      neutralized virus more potently when in an IgA backbone compared to an IgG
      backbone. In addition, HA-specific memory B cells isolated from human peripheral
      blood were more likely to be stalk specific when secreting antibodies of IgA
      isotypes compared to those secreting IgG. Taken together, our data provide strong
      evidence that HA stalk-binding antibodies perform optimally when in a polyclonal
      context and that the targeted elicitation of HA stalk-specific IgA should be an
      important consideration during "universal" influenza virus vaccine design.
      IMPORTANCE: Influenza viruses remain one of the most worrisome global public
      health threats due to their capacity to cause pandemics. While seasonal vaccines
      fail to protect against the emergence of pandemic strains, a new class of broadly
      neutralizing antibodies has been recently discovered and may be the key to
      developing a "universal" influenza virus vaccine. While much has been learned
      about the biology of these antibodies, most studies have focused only on
      monoclonal antibodies of IgG subtypes. However, the study of monoclonal
      antibodies often fails to capture the complexity of antibody functions that occur
      during natural polyclonal responses. Here, we provide the first detailed analyses
      of the biological activity of these antibodies in polyclonal contexts, comparing
      both IgG and IgA isotypes isolated from human donors. The striking differences
      observed in the functional properties of broadly neutralizing antibodies in
      polyclonal contexts will be essential for guiding design of "universal" influenza
      virus vaccines and therapeutics.

PMID- 25589656
TI  - The nsp1, nsp13, and M proteins contribute to the hepatotropism of murine
      coronavirus JHM.WU.
AB  - Mouse hepatitis virus (MHV) isolates JHM.WU and JHM.SD promote severe central
      nervous system disease. However, while JHM.WU replicates robustly and induces
      hepatitis, JHM.SD fails to replicate or induce pathology in the liver. These two
      JHM variants encode homologous proteins with few polymorphisms, and little is
      known about which viral proteins(s) is responsible for the liver tropism of
      JHM.WU. We constructed reverse genetic systems for JHM.SD and JHM.WU and,
      utilizing these full-length cDNA clones, constructed chimeric viruses and mapped
      the virulence factors involved in liver tropism. Exchanging the spike proteins of
      the two viruses neither increased replication of JHM.SD in the liver nor
      attenuated JHM.WU. By further mapping, we found that polymorphisms in JHM.WU
      structural protein M and nonstructural replicase proteins nsp1 and nsp13 are
      essential for liver pathogenesis. M protein and nsp13, the helicase, of JHM.WU
      are required for efficient replication in vitro and in the liver in vivo. The
      JHM.SD nsp1 protein contains a K194R substitution of Lys194, a residue conserved
      among all other MHV strains. The K194R polymorphism has no effect on in vitro
      replication but influences hepatotropism, and introduction of R194K into JHM.SD
      promotes replication in the liver. Conversely, a K194R substitution in nsp1 of
      JHM.WU or A59, another hepatotropic strain, significantly attenuates replication
      of each strain in the liver and increases IFN-beta expression in macrophages in
      culture. Our data indicate that both structural and nonstructural proteins
      contribute to MHV liver pathogenesis and support previous reports that nsp1 is a
      Betacoronavirus virulence factor. IMPORTANCE: The Betacoronavirus genus includes
      human pathogens, some of which cause severe respiratory disease. The spread of
      severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East
      respiratory syndrome coronavirus (MERS-CoV) into human populations demonstrates
      the zoonotic potential of emerging coronaviruses, and there are currently no
      vaccines or effective antivirals for human coronaviruses. Thus, it is important
      to understand the virus-host interaction that regulates coronavirus pathogenesis.
      Murine coronavirus infection of mice provides a useful model for the study of
      coronavirus-host interactions, including the determinants of tropism and
      virulence. We found that very small changes in coronavirus proteins can
      profoundly affect tropism and virulence. Furthermore, the hepatotropism of MHV
      JHM depends not on the spike protein and viral entry but rather on a combination
      of the structural protein M and nonstructural replicase-associated proteins nsp1
      and nsp13, which are conserved among betacoronaviruses. Understanding virulence
      determinants will aid in the design of vaccines and antiviral strategies.

PMID- 25589657
TI  - A host susceptibility gene, DR1, facilitates influenza A virus replication by
      suppressing host innate immunity and enhancing viral RNA replication.
AB  - Influenza A virus (IAV) depends on cellular factors to complete its replication
      cycle; thus, investigation of the factors utilized by IAV may facilitate
      antiviral drug development. To this end, a cellular transcriptional repressor,
      DR1, was identified from a genome-wide RNA interference (RNAi) screen. Knockdown
      (KD) of DR1 resulted in reductions of viral RNA and protein production,
      demonstrating that DR1 acts as a positive host factor in IAV replication. Genome
      wide transcriptomic analysis showed that there was a strong induction of
      interferon-stimulated gene (ISG) expression after prolonged DR1 KD. We found that
      beta interferon (IFN-beta) was induced by DR1 KD, thereby activating the JAK-STAT
      pathway to turn on ISG expression, which led to a strong inhibition of IAV
      replication. This result suggests that DR1 in normal cells suppresses IFN
      induction, probably to prevent undesired cytokine production, but that this
      suppression may create a milieu that favors IAV replication once cells are
      infected. Furthermore, biochemical assays of viral RNA replication showed that
      DR1 KD suppressed viral RNA replication. We also showed that DR1 associated with
      all three subunits of the viral RNA-dependent RNA polymerase (RdRp) complex,
      indicating that DR1 may interact with individual components of the viral RdRp
      complex to enhance viral RNA replication. Thus, DR1 may be considered a novel
      host susceptibility gene for IAV replication via a dual mechanism, not only
      suppressing the host defense to indirectly favor IAV replication but also
      directly facilitating viral RNA replication. IMPORTANCE: Investigations of virus
      host interactions involved in influenza A virus (IAV) replication are important
      for understanding viral pathogenesis and host defenses, which may manipulate
      influenza virus infection or prevent the emergence of drug resistance caused by a
      high error rate during viral RNA replication. For this purpose, a cellular
      transcriptional repressor, DR1, was identified from a genome-wide RNAi screen as
      a positive regulator in IAV replication. In the current studies, we showed that
      DR1 suppressed the gene expression of a large set of host innate immunity genes,
      which indirectly facilitated IAV replication in the event of IAV infection.
      Besides this scenario, DR1 also directly enhanced the viral RdRp activity, likely
      through associating with individual components of the viral RdRp complex. Thus,
      DR1 represents a novel host susceptibility gene for IAV replication via multiple
      functions, not only suppressing the host defense but also enhancing viral RNA
      replication. DR1 may be a potential target for drug development against influenza
      virus infection.

PMID- 25589658
TI  - Mining the human complexome database identifies RBM14 as an XPO1-associated
      protein involved in HIV-1 Rev function.
AB  - By recruiting the host protein XPO1 (CRM1), the HIV-1 Rev protein mediates the
      nuclear export of incompletely spliced viral transcripts. We mined data from the
      recently described human nuclear complexome to identify a host protein, RBM14,
      which associates with XPO1 and Rev and is involved in Rev function. Using a Rev
      dependent p24 reporter plasmid, we found that RBM14 depletion decreased Rev
      activity and Rev-mediated enhancement of the cytoplasmic levels of unspliced
      viral transcripts. RBM14 depletion also reduced p24 expression during viral
      infection, indicating that RBM14 is limiting for Rev function. RBM14 has
      previously been shown to localize to nuclear paraspeckles, a structure implicated
      in retaining unspliced HIV-1 transcripts for either Rev-mediated nuclear export
      or degradation. We found that depletion of NEAT1 RNA, a long noncoding RNA
      required for paraspeckle integrity, abolished the ability of overexpressed RBM14
      to enhance Rev function, indicating the dependence of RBM14 function on
      paraspeckle integrity. Our study extends the known host cell interactome of Rev
      and XPO1 and further substantiates a critical role for paraspeckles in the
      mechanism of action of Rev. Our study also validates the nuclear complexome as a
      database from which viral cofactors can be mined. IMPORTANCE: This study mined a
      database of nuclear protein complexes to identify a cellular protein named RBM14
      that is associated with XPO1 (CRM1), a nuclear protein that binds to the HIV-1
      Rev protein and mediates nuclear export of incompletely spliced viral RNAs.
      Functional assays demonstrated that RBM14, a protein found in paraspeckle
      structures in the nucleus, is involved in HIV-1 Rev function. This study
      validates the nuclear complexome database as a reference that can be mined to
      identify viral cofactors.

PMID- 25589659
TI  - Structural basis for host membrane remodeling induced by protein 2B of hepatitis
      A virus.
AB  - The complexity of viral RNA synthesis and the numerous participating factors
      require a mechanism to topologically coordinate and concentrate these multiple
      viral and cellular components, ensuring a concerted function. Similarly to all
      other positive-strand RNA viruses, picornaviruses induce rearrangements of host
      intracellular membranes to create structures that act as functional scaffolds for
      genome replication. The membrane-targeting proteins 2B and 2C, their precursor
      2BC, and protein 3A appear to be primarily involved in membrane remodeling.
      Little is known about the structure of these proteins and the mechanisms by which
      they induce massive membrane remodeling. Here we report the crystal structure of
      the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two
      domains: a C-terminal helical bundle preceded by an N-terminally curved five
      stranded antiparallel beta-sheet that displays striking structural similarity to
      the beta-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal
      arrangement of the protein molecules in the crystal provides a model for 2B
      induced host membrane remodeling during HAV infection. IMPORTANCE: No structural
      information is currently available for the 2B protein of any picornavirus despite
      it being involved in a critical process in viral factory formation: the
      rearrangement of host intracellular membranes. Here we present the structure of
      the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement,
      both in crystals and in solution under physiological conditions, can help to
      understand its function and sheds some light on the membrane rearrangement
      process, a putative target of future antiviral drugs. Moreover, this first
      structure of a picornaviral 2B protein also unveils a closer evolutionary
      relationship between the hepatovirus and enterovirus genera within the
      Picornaviridae family.

PMID- 25589660
TI  - Generation of a transgenic mouse model of Middle East respiratory syndrome
      coronavirus infection and disease.
AB  - The emergence of Middle East respiratory syndrome-coronavirus (MERS-CoV) in the
      Middle East since 2012 has caused more than 900 human infections with ~40%
      mortality to date. Animal models are needed for studying pathogenesis and for
      development of preventive and therapeutic agents against MERS-CoV infection.
      Nonhuman primates (rhesus macaques and marmosets) are expensive models of limited
      availability. Although a mouse lung infection model has been described using
      adenovirus vectors expressing human CD26/dipeptidyl peptidase 4 (DPP4), it is
      believed that a transgenic mouse model is needed for MERS-CoV research. We have
      developed this transgenic mouse model as indicated in this study. We show that
      transgenic mice globally expressing hCD26/DPP4 were fully permissive to MERS-CoV
      infection, resulting in relentless weight loss and death within days
      postinfection. High infectious virus titers were recovered primarily from the
      lungs and brains of mice at 2 and 4 days postinfection, respectively, whereas
      viral RNAs were also detected in the heart, spleen, and intestine, indicating a
      disseminating viral infection. Infected Tg(+) mice developed a progressive
      pneumonia, characterized by extensive inflammatory infiltration. In contrast, an
      inconsistent mild perivascular cuffing was the only pathological change
      associated with the infected brains. Moreover, infected Tg(+) mice were able to
      activate genes encoding for many antiviral and inflammatory mediators within the
      lungs and brains, coinciding with the high levels of viral replication. This new
      and unique transgenic mouse model will be useful for furthering knowledge of MERS
      pathogenesis and for the development of vaccine and treatments against MERS-CoV
      infection. IMPORTANCE: Small and economical animal models are required for the
      controlled and extensive studies needed for elucidating pathogenesis and
      development of vaccines and antivirals against MERS. Mice are the most desirable
      small-animal species for this purpose because of availability and the existence
      of a thorough knowledge base, particularly of genetics and immunology. The
      standard small animals, mice, hamsters, and ferrets, all lack the functional MERS
      CoV receptor and are not susceptible to infection. So, initial studies were done
      with nonhuman primates, expensive models of limited availability. A mouse lung
      infection model was described where a mouse adenovirus was used to transfect lung
      cells for receptor expression. Nevertheless, all generally agree that a
      transgenic mouse model expressing the DPP4 receptor is needed for MERS-CoV
      research. We have developed this transgenic mouse model as indicated in this
      study. This new and unique transgenic mouse model will be useful for furthering
      MERS research.

PMID- 25589662
TI  - Emergence and evolution of H10 subtype influenza viruses in poultry in China.
AB  - The cases of human infections with H10N8 viruses identified in late 2013 and
      early 2014 in Jiangxi, China, have raised concerns over the origin, prevalence,
      and development of these viruses in this region. Our long-term influenza
      surveillance of poultry and migratory birds in southern China in the past 12
      years showed that H10 influenza viruses have been introduced from migratory to
      domestic ducks over several winter seasons at sentinel duck farms at Poyang Lake,
      where domestic ducks share their water body with overwintering migratory birds.
      H10 viruses were never detected in terrestrial poultry in our survey areas until
      August 2013, when they were identified at live-poultry markets in Jiangxi. Since
      then, we have isolated 124 H10N8 or H10N6 viruses from chickens at local markets,
      revealing an ongoing outbreak. Phylogenetic analysis of H10 and related viruses
      showed that the chicken H10N8 viruses were generated through multiple
      reassortments between H10 and N8 viruses from domestic ducks and the enzootic
      chicken H9N2 viruses. These chicken reassortant viruses were highly similar to
      the human isolate, indicating that market chickens were the source of human
      infection. Recently, the H10 viruses further reassorted, apparently with H5N6
      viruses, and generated an H10N6 variant. The emergence and prevalence of H10
      viruses in chickens and the occurrence of human infections provide direct
      evidence of the threat from the current influenza ecosystem in China. IMPORTANCE:
      After the outbreak of avian-origin H7N9 influenza viruses in China, fatal human
      infections with a novel H10N8 virus were reported. Utilizing data from 12 years
      of influenza surveillance in southern China, we showed that H10 viruses were
      regularly introduced by migratory ducks to domestic ducks on Poyang Lake, a major
      aggregative site of migratory birds in Asia. The H10 viruses were maintained and
      amplified in domestic ducks and then transmitted to chickens and reassorted with
      enzootic H9N2 viruses, leading to an outbreak and human infections at live
      poultry markets. The emergence of the H10N8 virus, following a pathway similar to
      that of the recent H7N9 virus, highlights the role of domestic ducks and the
      current influenza ecosystem in China that facilitates influenza viruses moving
      from their reservoir hosts through the live-poultry system to cause severe
      consequences for public health.

PMID- 25589661
TI  - Early function of the Abutilon mosaic virus AC2 gene as a replication brake.
AB  - The C2/AC2 genes of monopartite/bipartite geminiviruses of the genera Begomovirus
      and Curtovirus encode important pathogenicity factors with multiple functions
      described so far. A novel function of Abutilon mosaic virus (AbMV) AC2 as a
      replication brake is described, utilizing transgenic plants with dimeric inserts
      of DNA B or with a reporter construct to express green fluorescent protein (GFP).
      Their replicational release upon AbMV superinfection or the individual and
      combined expression of epitope-tagged AbMV AC1, AC2, and AC3 was studied. In
      addition, the effects were compared in the presence and in the absence of an
      unrelated tombusvirus suppressor of silencing (P19). The results show that AC2
      suppresses replication reproducibly in all assays and that AC3 counteracts this
      effect. Examination of the topoisomer distribution of supercoiled DNA, which
      indicates changes in the viral minichromosome structure, did not support any
      influence of AC2 on transcriptional gene silencing and DNA methylation. The
      geminiviral AC2 protein has been detected here for the first time in plants. The
      experiments revealed an extremely low level of AC2, which was slightly increased
      if constructs with an intron and a hemagglutinin (HA) tag in addition to P19
      expression were used. AbMV AC2 properties are discussed with reference to those
      of other geminiviruses with respect to charge, modification, and size in order to
      delimit possible reasons for the different behaviors. IMPORTANCE: The (A)C2 genes
      encode a key pathogenicity factor of begomoviruses and curtoviruses in the plant
      virus family Geminiviridae. This factor has been implicated in the resistance
      breaking observed in agricultural cotton production. AC2 is a multifunctional
      protein involved in transcriptional control, gene silencing, and regulation of
      basal biosynthesis. Here, a new function of Abutilon mosaic virus AC2 in
      replication control is added as a feature of this protein in viral
      multiplication, providing a novel finding on geminiviral molecular biology.

PMID- 25589663
TI  - Conserved molecular signatures in gp120 are associated with the genetic
      bottleneck during simian immunodeficiency virus (SIV), SIV-human immunodeficiency
      virus (SHIV), and HIV type 1 (HIV-1) transmission.
AB  - Human immunodeficiency virus (HIV) transmission typically results from infection
      by a single transmitted/founder (T/F) variant. Are T/F variants chosen uniformly
      at random from the donor pool, or are they selected based on advantageous traits
      facilitating transmission? Finding evidence for selection during transmission is
      of particular interest, because it would indicate that phenotypic and/or genetic
      properties of the viruses might be harnessed as potential vaccine targets or
      immunotherapies. Here, we systematically evaluated the differences between the
      Env proteins of simian immunodeficiency virus/simian HIV (SIV/SHIV) stock and T/F
      variants in search of "signature" sites of transmission. We also surveyed residue
      preferences in HIV at the SIV/SHIV signature sites. Four sites of gp120 showed
      significant selection, and an additional two sites showed a similar trend.
      Therefore, the six sites clearly differentiate T/F viruses from the majority of
      circulating variants in the stocks. The selection of SIV/SHIV could be inferred
      reasonably across both vaccinated and unvaccinated subjects, with infections
      resulting from vaginal, rectal, and intravenous routes of transmission and
      regardless of viral dosage. The evidence for selection in SIV and SHIV T/F
      variants is strong and plentiful, and in HIV the evidence is suggestive though
      commensurate with the availability of suitable data for analysis. Two of the
      signature residues are completely conserved across the SIV, SHIV, and HIV
      variants we examined. Five of the signature residues map to the C1 region of
      gp120 and one to the signal peptide. Our data raise the possibility that C1,
      while governing the association between gp120 and gp41, modulates transmission
      efficiency, replicative fitness, and/or host cell tropism at the level of virus
      cell attachment and entry. IMPORTANCE: The present study finds significant
      evidence of selection on gp120 molecules of SIV/SHIV T/F viruses. The data
      provide ancillary evidence suggesting the same sites are under selection in HIV.
      Our findings suggest that the signature residues are involved in increasing the
      transmissibility of infecting viruses; therefore, they are potential targets for
      developing a vaccine or other protective measures. A recent study identified the
      same T/F signature motif but interpreted it as an effect of neutralization
      resistance. Here, we show that the T/F motif has broader functional significance
      beyond neutralization sensitivity, because it is present in nonimmune subjects.
      Also, a vaccine regimen popular in animal trials might have increased the
      transmission of variants with otherwise low transmission fitness. Our
      observations might explain why many animal vaccine trials have not faithfully
      predicted outcomes in human vaccine trials and suggest that current practices in
      vaccine design need to be reexamined accordingly.

PMID- 25589665
TI  - Resection of gliomas around language areas:  can fMRI contribute?

PMID- 25589664
TI  - New insights into the evolutionary rate of hepatitis B virus at different
      biological scales.
AB  - The evolutionary rates of hepatitis B virus (HBV) estimated using contemporary
      sequences are 10(2) to 10(4) times higher than those derived from archaeological
      and genetic evidence. This discrepancy makes the origin of HBV and the time scale
      of its spread, both of which are critical for studying the burden of HBV
      pathogenicity, largely unresolved. To evaluate whether the dual demands (i.e.,
      adaptation within hosts and colonization between hosts) of the viral life cycle
      affect this conundrum, the HBV quasispecies dynamics within and among hosts from
      a family consisting of a grandmother, her 5 children, and her 2 granddaughters,
      all of whom presumably acquired chronic HBV through mother-to-infant
      transmission, were examined by PCR cloning and next-generation sequencing
      methods. We found that the evolutionary rate of HBV between hosts was
      considerably lower than that within hosts. Moreover, the between-host
      substitution rates of HBV decreased as transmission numbers between individuals
      increased. Both observations were due primarily to changes at nonsynonymous
      rather than synonymous sites. There were significantly more multiple
      substitutions than expected for random mutation processes, and 97% of
      substitutions were changed from common to rare amino acid residues in the
      database. Continual switching between colonization and adaptation resulted in a
      rapid accumulation of mutations at a limited number of positions, which quickly
      became saturated, whereas substitutions at the remaining regions occurred at a
      much lower rate. Our study may help to explain the time-dependent HBV
      substitution rates reported in the literature and provide new insights into the
      origin of the virus. IMPORTANCE: It is known that the estimated hepatitis B virus
      (HBV) substitution rate is time dependent, but the reason behind this observation
      is still elusive. We hypothesize that owing to the small genome size of HBV,
      transmission between hosts and adaptation within hosts must exhibit high levels
      of fitness trade-offs for the virus. By studying the HBV quasispecies dynamics
      for a chain of sequentially infected transmissions within a family, we found the
      HBV substitution rate between patients to be negatively correlated with the
      number of transmissions. Continual switching between hosts resulted in a rapid
      accumulation of mutations at a limited number of genomic sites, which quickly
      became saturated in the short term. Nevertheless, substitutions at the remaining
      regions occurred at a much lower rate. Therefore, the HBV substitution rate
      decreased as the divergence time increased.

PMID- 25589667
TI  - Three-tesla functional MR language mapping: comparison with direct cortical
      stimulation in gliomas.
AB  - OBJECTIVE: To evaluate the accuracy of functional MRI (fMRI) at 3T, as currently
      used in the preoperative mapping of language areas, compared with direct cortical
      stimulation (DCS) during awake surgery, in patients with supratentorial gliomas;
      and to identify clinical, histopathologic,and radiologic factors associated with
      fMRI/DCS discrepancies. METHODS: Language mapping with fMRI and DCS of 40
      consecutive patients with gliomas(24 low-grade, 16 high-grade) in functional
      areas were retrospectively analyzed. Three block designed tasks were performed
      during fMRI (letter word generation, category word generation,semantic
      association). During awake surgery, eloquent areas were mapped using DCS, blinded
      to fMRI. A site-by-site comparison of the 2 techniques was performed using a
      cortical grid. fMRI sensitivity and specificity were calculated using DCS as the
      reference. Associations of clinical,histopathologic, and radiologic features
      (including relative cerebral blood volume [rCBV] measured with dynamic
      susceptibility contrast MRI) with fMRI false-positive and false-negative
      occurrence were assessed using hierarchical logistic regressions. RESULTS: Of
      2,114 stimulated cortical sites, 103 were positive for language during DCS.
      Sensitivity and specificity of language fMRI combining the 3 tasks reached 37.1%
      (95% confidence interval [CI] 20.7-57.2) and 83.4% (95% CI 77.1-88.3),
      respectively. Astrocytoma subtype(odds ratio [OR] 2.50 [1.32-4.76]; p 5 0.007),
      tumor rCBV ,1.5 (OR 2.17 [1.08-4.35]; p 50.03), higher cortical rCBV (OR 2.22
      [1.15-4.17]; p 5 0.02), and distance to tumor .1 cm (OR2.46 [1.82-3.32]; p #
      0.001) were independently associated with fMRI false-positive occurrence.
      CONCLUSIONS: There are pitfalls in preoperative fMRI as currently used in
      preoperative language mapping in glioma patients, made more complicated when high
      grade and hyperperfused tumors are evaluated.

PMID- 25589666
TI  - Colonic mucosal a-synuclein lacks  specificity as a biomarker for Parkinson 
      disease.
AB  - OBJECTIVE: To determine the utility of detecting a-synuclein (aSyn) in colonic
      mucosal biopsy tissue as a potential diagnostic biomarker for Parkinson disease
      (PD). METHODS: We used the paraffin-embedded tissue (PET) blot, which degrades
      physiologic nonaggregated aSyn using proteinase K and enhances antigen retrieval
      allowing sensitive and selective detection of remaining protein aggregates, to
      detect aSyn in colonic mucosal biopsies from 15 patients with early PD (,3
      years), 7 patients with later PD (.5 years), and 11 individuals without PD. aSyn
      and serine 129-phosphorylated aSyn (Ser129p-aSyn) were assessed by PET blot and
      conventional immunohistochemistry. RESULTS: PET blot-resistant aggregated aSyn
      and Ser129p-aSyn was present in 12 of 15 individuals with early PD, 7 of 7
      individuals with later PD, and 11 of 11 control subjects. The number of biopsies
      positive by PET blot relative to conventional immunohistochemistry was
      significantly lower in both PD groups compared with the control group for both
      aSyn and Ser129p-aSyn,whereas routine immunohistochemistry was positive more
      often in PD, but was positive in as many as 9 of 11 control individuals.
      CONCLUSION: Strong evidence of the presence of aggregated hyperphosphorylated
      aSyn in individuals with and without PD, using such a sensitive and specific
      method as the PET blot, suggests that colonic deposition of aSyn is not a useful
      diagnostic test for PD. The utility of detecting aSynin the colon as a biomarker
      in combination with other assessments remains to be determined.

PMID- 25589668
TI  - On the origin of painful somatosensory  seizures.
AB  - OBJECTIVE: To explore whether painful somatosensory seizures (PSS) are generated
      in the primary somatosensory cortex (SI area) or in the operculo-insular cortex.
      METHODS: We analyzed ictal recordings and data from stimulation using
      intracerebral electrodes exploring the operculo-insular cortex (including
      secondary somatosensory [SII] region), SI area,and other areas of the pain matrix
      (cingulate gyrus and supplementary motor area) in a case series study of 5
      patients with PSS. RESULTS: Clinical features of PSS were different from those of
      seizures arising from the SI area: (1)pain intensity was higher; (2) pain
      spreading was not from one somatotopic territory to adjacentones; and (3) the
      spatial extent of pain was large, fitting better with the size of somatosensory
      receptive fields of the insula and SII region than of the SI area. The insula and
      SII region were systematically involved at the onset of seizures, rapidly
      followed by the opercular portion of SI area.The upper part of SI cortex was
      involved at a lesser degree, with some delay, and pain duration did not correlate
      in time with that of the discharge in SI. Ictal pain was consistently reproduced
      by stimulation of the insula or SII region but never by stimulating the SI area.
      CONCLUSIONS: These data strongly suggest that PSS originate in the operculo
      insular cortex and not in the SI area and corroborate the concept that this
      region is involved in the sensory discriminative processing of pain inputs. Pain
      at the onset of PSS has a high value for localizing the epileptogenic area.

PMID- 25589669
TI  - Gamma oscillations precede interictal epileptiform spikes in the seizure onset
      zone.
AB  - OBJECTIVE: To investigate the generation, spectral characteristics, and potential
      clinical significance of brain activity preceding interictal epileptiform spike
      discharges (IEDs) recorded with intracranial EEG. METHODS: Seventeen adult
      patients with drug-resistant temporal lobe epilepsy were implanted with
      intracranial electrodes as part of their evaluation for epilepsy surgery. IEDs
      detected on clinical macro- and research microelectrodes were analyzed using time
      frequency spectral analysis. RESULTS: Gamma frequency oscillations (30-100 Hz)
      often preceded IEDs in spatially confined brain areas. The gamma-IEDs were
      consistently observed 35 to 190 milliseconds before the epileptiform spike
      waveforms on individual macro- and microelectrodes. The gamma oscillations
      associated with IEDs had longer duration (p < 0.001) and slightly higher
      frequency (p = 0.045) when recorded on microelectrodes compared with clinical
      macroelectrodes. Although gamma-IEDs comprised only a subset of IEDs, they were
      strongly associated with electrodes in the seizure onset zone (SOZ) compared with
      the surrounding brain regions (p = 0.004), in sharp contrast to IEDs without
      preceding gamma oscillations that were often also detected outside of the SOZ.
      Similar to prior studies, isolated pathologic high-frequency oscillations in the
      gamma (30-100 Hz) and higher (100-600 Hz) frequency range, not associated with an
      IED, were also found to be associated with SOZ. CONCLUSIONS: The occurrence of
      locally generated gamma oscillations preceding IEDs suggests a mechanistic role
      for gamma in pathologic network activity generating IEDs. The results show a
      strong association between SOZ and gamma-IEDs. The potential clinical application
      of gamma-IEDs for mapping pathologic brain regions is intriguing, but will
      require future prospective studies.

PMID- 25589670
TI  - Lambert-Eaton syndrome IgG inhibits transmitter release via P/Q Ca2+ channels.
AB  - OBJECTIVE: To determine whether immunoglobulin G (IgG) from patients with Lambert
      Eaton myasthenic syndrome (LEMS) decreases action potential-evoked synaptic
      vesicle exocytosis,and whether the effect is mediated by P/Q-type voltage-gated
      calcium channels (VGCCs). METHODS: IgG was obtained from 4 patients with LEMS (3
      males, 1 female), including 2 patients with lung malignancy. Antibodies against
      P/Q-type VGCCs were detected in all 4 patients, and against N-type VGCCs in 2. We
      incubated neuronal cultures with LEMS IgG and determined the size of the total
      recycling pool of synaptic vesicles and the rate of action potential-evoked
      exocytosis using fluorescence imaging of the amphiphilic dye SynaptoRed C1.
      Pooled IgG from healthy volunteers was used as a control. We repeated the
      experiments on synapses lacking P/Q-type calcium channels from a Cacna1a knockout
      mouse to determine whether these channels account for the pathogenic effect of
      LEMS IgG. RESULTS: LEMS IgG had no effect on the total recycling pool size but
      significantly reduced the rate of action potential-evoked synaptic exocytosis in
      wild-type neurons when compared with neurons treated with control IgG. In
      contrast, LEMS IgG had no effect on the rate of synaptic vesicle exocytosis in
      neurons lacking P/Q-type channels. CONCLUSIONS: These data provide direct
      evidence that LEMS IgG inhibits neurotransmitter release by acting on P/Q-type
      VGCCs.

PMID- 25589671
TI  - "Noncognitive" symptoms of early Alzheimer disease: a longitudinal analysis.
AB  - OBJECTIVES: To observe the natural time course of noncognitive symptoms before
      the onset of symptomatic Alzheimer disease dementia. METHODS: Using the National
      Alzheimer's Coordinating Center Uniform Data Set from September 2005 to March
      2013, data from cognitively normal individuals who were aged 50 years or older at
      first visit and had subsequent follow-up were analyzed. Survival analyses were
      used to examine the development of particular symptoms relative to each other on
      the Neuropsychiatric Inventory Questionnaire (NPI-Q), Functional Activities
      Questionnaire, and Geriatric Depression Scale, and to compare the development of
      individual symptoms for persons who did and did not receive a Clinical Dementia
      Rating (CDR) .0 (indicating abnormal cognition) during the follow-up period.
      RESULTS: The order of symptom occurrence on the NPI-Q was similar for
      participants who remained at CDR 0 and for those who received a CDR .0 over the
      follow-up period, although the time to most NPI-Q symptoms was faster for
      participants who received a CDR.0 (p, 0.001).With the exception of memory,
      Geriatric Depression Scale symptoms reported by both CDR groups were similar.
      CONCLUSIONS: We found a significantly earlier presence of positive symptoms on
      the NPI-Q in cognitively normal patients who subsequently developed CDR .0. Among
      participants with no depression symptoms at baseline, results suggest that
      depressive symptoms may increase with aging regardless of incipient dementia.
      Such findings begin to delineate the noncognitive course of Alzheimer disease
      dementia in the preclinical stages. Future research must further elucidate the
      correlation between noncognitive changes and distinct dementia subtypes.

PMID- 25589672
TI  - Mouse models for assessing the cross-protective efficacy of oral non-typhoidal
      Salmonella vaccine candidates harbouring in-frame deletions of the ATP-dependent
      protease lon and other genes.
AB  - In BALB/c mouse models of Salmonella enterica serovar Typhimurium infection, a
      single oral immunization with a mutant strain with an insertion of the
      chloramphenicol resistance gene into the ATP-dependent protease clpP or lon gene
      decreased the number of salmonellae in each tissue sample 5 days after oral
      challenge with virulent S. Typhimurium at weeks 26 and 54 post-immunization.
      These data suggested that an oral immunization with the ClpP- or Lon-disrupted S.
      Typhimurium strain could provide long-term protection against oral challenge with
      virulent S. Typhimurium. Accordingly, recombinant oral non-typhoidal Salmonella
      (NTS) vaccines were constructed by incorporating mutants of both S. Typhimurium
      and S. enterica serovar Enteritidis harbouring stable in-frame markerless
      deletions of the clpP-lon-sulA (suppressor of lon), lon-sulA or lon-msbB
      (acyltransferase) genes. Amongst these orally administered vaccine candidates,
      those with the lon-sulA gene deletion mutants of S. Typhimurium and S.
      Enteritidis protected BALB/c and C57BL/6J mice against oral challenge with both
      virulent S. Typhimurium and virulent S. Enteritidis. Therefore, the in-frame
      markerless lon-sulA gene deletion mutant of S. Typhimurium or S. Enteritidis
      could be a promising cross-protective NTS live vaccine candidate for practical
      use in humans. 

PMID- 25589673
TI  - CLASP2-dependent microtubule capture at the neuromuscular junction membrane
      requires LL5beta and actin for focal delivery of acetylcholine receptor vesicles.
AB  - A hallmark of the neuromuscular junction (NMJ) is the high density of
      acetylcholine receptors (AChRs) in the postsynaptic muscle membrane. The
      postsynaptic apparatus of the NMJ is organized by agrin secreted from motor
      neurons. The mechanisms that underlie the focal delivery of AChRs to the adult
      NMJ are not yet understood in detail. We previously showed that microtubule (MT)
      capture by the plus end-tracking protein CLASP2 regulates AChR density at agrin
      induced AChR clusters in cultured myotubes via PI3 kinase acting through
      GSK3beta. Here we show that knockdown of the CLASP2-interaction partner LL5beta
      by RNAi and forced expression of a CLASP2 fragment blocking the CLASP2/LL5beta
      interaction inhibit microtubule capture. The same treatments impair focal vesicle
      delivery to the clusters. Consistent with these findings, knockdown of LL5beta at
      the NMJ in vivo reduces the density and insertion of AChRs into the postsynaptic
      membrane. MT capture and focal vesicle delivery to agrin-induced AChR clusters
      are also inhibited by microtubule- and actin-depolymerizing drugs, invoking both
      cytoskeletal systems in MT capture and in the fusion of AChR vesicles with the
      cluster membrane. Combined our data identify a transport system, organized by
      agrin through PI3 kinase, GSK3beta, CLASP2, and LL5beta, for precise delivery of
      AChR vesicles from the subsynaptic nuclei to the overlying synaptic membrane. 

PMID- 25589674
TI  - PDGF-stimulated dispersal of cell clusters and disruption of fibronectin matrix
      on three-dimensional collagen matrices requires matrix metalloproteinase-2.
AB  - Formation of cell clusters is a common morphogenic cell behavior observed during
      tissue and organ development and homeostasis, as well as during pathological
      disorders. Dynamic regulation of cell clustering depends on the balance between
      contraction of cells into clusters and migration of cells as dispersed
      individuals. Previously we reported that under procontractile culture conditions,
      fibronectin fibrillar matrix assembly by human fibroblasts functioned as a
      nucleation center for cell clustering on three-dimensional collagen matrices.
      Here we report that switching preformed cell clusters from procontractile to
      promigratory culture conditions results in cell dispersal out of clusters and
      disruption of FN matrix. Experiments using small interfering RNA silencing and
      pharmacological inhibition demonstrated that matrix metalloproteinase activity
      involving MMP-2 was necessary for fibronectin matrix disruption and dispersal of
      cell clusters. 

PMID- 25589675
TI  - Involvement of general control nonderepressible kinase 2 in cancer cell apoptosis
      by posttranslational mechanisms.
AB  - General control nonderepressible kinase 2 (GCN2) is a promising target for cancer
      therapy. However, the role of GCN2 in cancer cell survival or death is elusive;
      further, small molecules targeting GCN2 signaling are not available. By using a
      GCN2 level-based drug screening assay, we found that GCN2 protein level
      critically determined the sensitivity of the cancer cells toward Na(+),K(+)
      ATPase ligand-induced apoptosis both in vitro and in vivo, and this effect was
      largely dependent on C/EBP homologous protein (CHOP) induction. Further analysis
      revealed that GCN2 is a short-lived protein. In A549 lung carcinoma cells,
      cellular beta-arrestin1/2 associated with GCN2 and maintained the GCN2 protein
      level at a low level by recruiting the E3 ligase NEDD4L and facilitating
      consequent proteasomal degradation. However, Na(+),K(+)-ATPase ligand treatment
      triggered the phosphorylation of GCN2 at threonine 899, which increased the GCN2
      protein level by disrupting the formation of GCN2-beta-arrestin-NEDD4L ternary
      complex. The enhanced GCN2 level, in turn, aggravated Na(+),K(+)-ATPase ligand
      induced cancer cell apoptosis. Our findings reveal that GCN2 can exert its
      proapoptotic function in cancer cell death by posttranslational mechanisms.
      Moreover, Na(+),K(+)-ATPase ligands emerge as the first identified small-molecule
      drugs that can trigger cancer cell death by modulating GCN2 signaling. 

PMID- 25589676
TI  - Reactions to FDA-Proposed Graphic Warning Labels Affixed to U.S. Smokers'
      Cigarette Packs.
AB  - INTRODUCTION: Graphic warning labels have been shown to be more effective than
      text-only labels in increasing attention and perceived health risks, but most
      U.S. studies have involved single exposures in laboratory or Internet settings.
      METHODS: We recruited a convenience sample (N = 202) of U.S. adult smokers from
      population subgroups with higher rates of smoking and smoking-related deaths who
      had participated in a larger survey about graphic warning labels. Participants
      were randomized to get 1 of 9 graphic + text labels or a text-only label.
      Research staff affixed a warning label sticker to participants' cigarette pack(s)
      at enrollment. Color graphic labels covered slightly more than the lower half of
      packs. Black and white labels of current U.S. text-only warnings covered the
      existing side warning to prompt attention to the label (i.e., attention control).
      Participants received extra stickers of the same label for subsequent packs, and
      completed 3 telephone interviews in 1 week. RESULTS: Participants reported low
      avoidance (<34%) and consistent use of the stickers (91%). Smokers consistently
      paid more attention to graphic than text-only labels. Only 5 of the 9 graphic
      warning labels were significantly associated with greater thoughts of health
      risks. Thinking about quitting and stopping smoking did not differ by label.
      Qualitative data illustrated differences in the "stickiness," self-referencing,
      and counterarguments of graphic warning labels. CONCLUSIONS: U.S. smokers'
      reactions to graphic warning labels on their own packs were similar to other,
      more controlled studies. Qualitative findings underscore the need for warning
      labels that encourage self-referential processing without increasing defensive
      reactions.

PMID- 25589677
TI  - The Nicotine Metabolite Ratio in Pregnancy Measured by trans-3'-Hydroxycotinine
      to Cotinine Ratio: Characteristics and Relationship With Smoking Cessation.
AB  - INTRODUCTION: Nicotine replacement therapy (NRT) helps nonpregnant smokers quit,
      but there is no evidence that standard dose NRT is effective in pregnancy. As
      nicotine metabolism increases in pregnancy, this could reduce NRT efficacy. Using
      the ratio of trans-3'-hydroxycotinine to cotinine, the nicotine metabolite ratio
      (NMR), we investigated relationships between the rate of nicotine metabolism,
      maternal characteristics and smoking cessation in pregnant women recruited to a
      randomized controlled trial of NRT. METHODS: Data from 1,050 pregnant smokers in
      the Smoking, Nicotine and Pregnancy trial who were of 12-24 weeks gestation had
      exhaled carbon monoxide readings of >=8 ppm at recruitment and who were
      randomized to NRT or placebo patches were used. Linear and logistic regression
      investigated associations between maternal characteristics and NMR and also
      between NMR and subsequent validated cessation from smoking. RESULTS: Six hundred
      and sixty-two women (63%) provided blood samples for NMR estimation. Higher NMR
      was associated with increased cigarette consumption prior to pregnancy. At 1
      month (odds ratio [OR] = 0.87; 95% CI = 0.76-0.99; p = .043) and delivery (OR =
      0.79; 95% CI = 0.66-0.95; p = .010), there was a significant negative association
      between a 0.1 unit increase in NMR and odds of achieving cessation after
      adjusting for possible confounders. There was no evidence for an interaction
      between a 0.1 unit increase in NMR and treatment assignment on the odds of
      cessation at 1 month post-quit date (p = .556). CONCLUSION: Pregnant women who
      metabolize nicotine more rapidly are less likely to achieve cessation when they
      try to quit smoking. There is no evidence that NRT is more effective in women who
      metabolize nicotine more slowly.

PMID- 25589678
TI  - Use of E-Cigarettes Among Current Smokers: Associations Among Reasons for Use,
      Quit Intentions, and Current Tobacco Use.
AB  - INTRODUCTION: Research has documented growing availability and use of e
      cigarettes in the United States over the last decade. METHODS: We conducted a
      national panel survey of current adult cigarette smokers to assess attitudes,
      beliefs, and behaviors relating to e-cigarette use in the United States (N =
      2,254). RESULTS: Among current cigarette smokers, 20.4% reported current use of e
      cigarettes on some days and 3.7% reported daily use. Reported reasons for e
      cigarette use included: quit smoking (58.4%), reduce smoking (57.9%), and reduce
      health risks (51.9%). No significant differences in sociodemographic
      characteristics between e-cigarette users and nonusers were observed. Prior quit
      attempts were reported more frequently among e-cigarette users (82.8%) than
      nonusers (74.0%). Intention to quit was reported more frequently among e
      cigarette users (64.7%) than nonusers (46.8%). Smokers intending to quit were
      more likely to be e-cigarette users than those not intending to quit (odds ratio
      [OR] = 1.90, CI =1.36-2.65). Those who used e-cigarettes to try to quit smoking
      (OR = 2.25, CI = 1.25-4.05), reduce stress (OR = 3.66, CI = 1.11-12.09), or
      because they cost less (OR = 3.42, CI = 1.64-7.13) were more likely to report
      decreases in cigarette smoking than those who did not indicate these reasons.
      Smokers who reported using e-cigarettes to quit smoking (OR = 16.25, CI = 8.32
      31.74) or reduce stress (OR = 4.30, CI = 1.32-14.09) were significantly more
      likely to report an intention to quit than those who did not indicate those
      reasons for using e-cigarettes. CONCLUSIONS: Nearly a quarter of smokers in our
      study reported e-cigarettes use, primarily motivated by intentions to quit or
      reduce smoking. These findings identify a clinical and public health opportunity
      to re-engage smokers in cessation efforts.

PMID- 25589679
TI  - Smoking Among Sexual Minorities: Are There Racial Differences?
AB  - INTRODUCTION: Smoking prevalence is higher among sexual minorities compared to
      their heterosexual peers. However, very little is known about potential racial
      differences in smoking among sexual minority populations. We examined differences
      by race in smoking status among a robust sample of sexual minorities. METHODS: We
      used data from the 2010 Social Justice Sexuality project, a large national
      convenience sample of sexual minority adults that oversampled individuals from
      racial minority groups. Log-Poisson multivariable regression models were employed
      to determine the risk of current smoking among sexual minority individuals by
      race after controlling for socio-demographic characteristics. RESULTS: Among
      smokers, 22.35% identified as White, 26.98% identified as Black, 19.38%
      identified as Latino/Hispanic, 5.58% identified as Asian American, and 25.67%
      were other/multiracial. In fully adjusted gender stratified models, Black men
      (adjusted risk ratio [aRR] = 0.61, 95% confidence interval [CI] = 0.50, 0.75) and
      Asian American men (aRR = 0.61, 95% CI = 0.50, 0.75) were at lower risk of
      smoking compared to White men. Black women were the only to remain statistically
      significant for decreased risk of smoking in fully adjusted gender stratified
      models (aRR = 0.78, 95 % CI = 0.65, 0.95). CONCLUSIONS: Among sexual minorities,
      Black and Asian American individuals consistently were at decreased risk of
      current smoking compared to their White peers. Future research should seek to
      understand the mechanisms that contribute to decreased smoking status among
      racial sexual minorities.

PMID- 25589681
TI  - Correction.

PMID- 25589682
TI  - Correction.

PMID- 25589680
TI  - Does Extended Pre Quit Bupropion Aid in Extinguishing Smoking Behavior?
AB  - INTRODUCTION: Understanding the mechanisms by which bupropion promotes smoking
      cessation may lead to more effective treatment. To the extent that reduced
      smoking reinforcement is one such mechanism, a longer duration of pre quit
      bupropion treatment should promote extinction of smoking behavior. We evaluated
      whether 4 weeks of pre quit bupropion (extended run-in) results in greater pre
      quit reductions in smoking rate and cotinine and, secondarily, greater short-term
      abstinence, than standard 1 week of pre quit bupropion (standard run-in).
      METHODS: Adult smokers (n = 95; 48 females) were randomized to a standard run-in
      group (n = 48; 3-week placebo, then 1-week bupropion pre quit) or an extended run
      in group (4-week pre quit bupropion; n = 47). Both groups received group
      behavioral counseling and 7 weeks of post quit bupropion. Smoking rate (and
      craving, withdrawal, and subjective effects) was collected daily during the pre
      quit period; biochemical data (cotinine and carbon monoxide) were collected at
      study visits. RESULTS: During the pre quit period, the extended run-in group
      exhibited a greater decrease in smoking rate, compared to the standard run-in
      group, interaction p = .03. Cigarette craving and salivary cotinine followed a
      similar pattern, though the latter was evident only among women. Biochemically
      verified 4-week continuous abstinence rates were higher in the extended run-in
      group (53%) than the standard run-in group (31%), p = .033. CONCLUSIONS: The
      extended use of bupropion prior to a quit attempt reduces smoking behavior during
      the pre quit period and improved short-term abstinence rates. The data are
      consistent with an extinction-of-reinforcement model and support further
      investigation of extended run-in bupropion therapy for smoking cessation.

PMID- 25589684
TI  - Correction.

PMID- 25589683
TI  - Correction.

PMID- 25589685
TI  - Correction.

PMID- 25589686
TI  - Correction.

PMID- 25589687
TI  - Correction.

PMID- 25589689
TI  - Correction.

PMID- 25589688
TI  - Author's response: What characteristics of primary care and patients are
      associated with early death in patients with lung cancer in the UK?

PMID- 25589690
TI  - Correction.

PMID- 25589691
TI  - Correction.

PMID- 25589693
TI  - Recanalization of popliteal and infrapopliteal chronic total occlusions using
      Viance and CrossBoss crossing catheters: a multicenter experience from the XLPAD
      Registry.
AB  - BACKGROUND: Chronic total occlusions (CTOs) are reported in up to 40% of patients
      with symptomatic peripheral arterial disease. The Viance Crossing catheter
      (Covidien) and the CrossBoss catheter (Boston Scientific) are novel devices that
      facilitate either true lumen or subintimal navigation across CTOs. The purpose of
      this study was to examine the acute procedural success of these devices for
      popliteal and below-the-knee (BTK) CTOs. METHODS: Clinical and procedural outcome
      data between Sept 2010 and October 2013 were analyzed from the ongoing
      multicenter XLPAD registry. Technical success was defined as true lumen passage
      of the catheter, while procedural success was defined as successful vessel
      revascularization inclusive of subintimal passage and reentry. RESULTS: Twenty
      nine patients underwent 31 procedures, in which 37 lesions were treated with the
      Viance and CrossBoss catheters. Mean age of the group was 69.1 +/- 10.7 years and
      26 patients were male (90%). All patients (100%) had hypertension, 62% were
      diabetic, and 48% were active smokers. Critical limb ischemia was the indication
      for the procedure in 58% of cases; mean Rutherford class was 4.2 +/- 1.2 for the
      entire cohort. Target CTOs included 14 anterior tibial, 9 posterior tibial, 5
      peroneal, 1 tibio-peroneal trunk, and 8 popliteal artery lesions. Mean lesion
      length was 81 +/- 64 mm; 15 lesions (41%) were severely calcified. True lumen
      passage was obtained in 24 lesions (65% technical success). Subintimal entry was
      achieved in 5 lesions (14%). Procedural success was achieved in 26 lesions (70%).
      Procedural failure was related to longer lesion length (P<.001), and mean length
      of failed lesions was 136 +/- 65 mm. CONCLUSION: Viance and CrossBoss catheters
      were associated with an overall 70% procedural success with predominantly true
      lumen crossing in a BTK-CTO cohort. CTO length remains an important determinant
      of device success.

PMID- 25589694
TI  - Angiographic profile and endovascular interventions in Takayasu's arteritis.
AB  - BACKGROUND: Takayasu's arteritis (TA) is a rare inflammatory, granulomatous
      vasculitis primarily involving the aorta and its major branches. Clinical and
      angiographic manifestations of the disease differ in various parts of the world.
      OBJECTIVES: To analyze the clinical features, angiographic profile, and
      endovascular interventions in TA patients (pts). METHODS: From January 2009 to
      March 2013, a total of 62 consecutive pts who were diagnosed with Takayasu's
      arteritis at our institute based on American College of Rheumatology Criteria
      were included in the study. Thirty-four pts underwent conventional angiography,
      while 28 were evaluated using computed tomographic angiography. Endovascular
      interventions were attempted for 24 lesions in 23 pts who were symptomatic and
      had significant stenotic lesions. RESULTS: The mean age of presentation was 28.4
      +/- 9.7 years, with 69.4% female. Limb claudication (52%) was the most common
      presenting symptom, followed by vertigo (35%) and constitutional symptoms. The
      most common angiography class was type V (37.1%), followed by type I (32.2%),
      type IV (17.7%), type IIa (8.1%), type III (3.2%), and type IIb (1.6%). The most
      common artery involved was the subclavian (64.5%), with the left subclavian more
      commonly involved than the right, followed by the abdominal aorta (51.6%) and
      renal artery (32.2%). Stenotic lesions were present in 59 pts (95%), while
      aneurysmal involvement was seen in 17 (27.4%), with isolated aneurysmal
      involvement in 3 of these. CONCLUSIONS: Our cohort of TA pts had more severe and
      widespread involvement. Despite a more advanced presentation, percutaneous
      balloon angioplasty with stent implantation is feasible, with good immediate
      results but slightly higher complication rates.

PMID- 25589695
TI  - Stent and Non-Stent Based Outcomes of Infrainguinal Peripheral Artery
      Interventions From the Multicenter XLPAD Registry.
AB  - BACKGROUND: There are limited data regarding contemporary use of stent and non
      stent based treatment strategies of infrainguinal peripheral artery disease
      (PAD). METHODS: We analyzed data from the ongoing multicenter XLPAD registry
      between July 2005 and October 2013 to report on the use of non-stent (atherectomy
      +/- balloon angioplasty) and stent-based treatment of superficial femoral artery
      (SFA), popliteal, and below-the-knee (BTK) vessels in contemporary clinical
      practice. RESULTS: A total of 584 interventions (SFA, 82.5%; popliteal, 7.2%;
      BTK, 9.9%) were performed in 372 patients (mean age, 63.2 years; diabetes
      mellitus, 57.7%; Rutherford category 1-3, 73.5%; Rutherford category 4-6, 20.1%).
      Stents were deployed in 389 lesions (66.6%; SFA, 90.5%; popliteal, 5.1%; BTK,
      4.1%) and non-stent strategy (atherectomy, 49%) in 195 lesions (33.4%; SFA,
      66.7%; popliteal, 11.3%; BTK, 21.5%). In the stent and non-stent groups, mean
      lesion lengths were 133.9 mm and 86.0 mm (P<.001), chronic total occlusions
      (CTOs) constituted 63.0% and 49.7% (P<.01), and restenotic lesions were 12.6% and
      32.3% (P<.001), respectively. At a mean follow-up of 260 +/- 130 days, in the
      stent and non-stent treated patients, all-cause mortality was 4.3% and 3.5%
      (P=.65), clinically indicated repeat revascularization was 17.5% and 14.9%
      (P=.42), and amputation was 4.6% and 9.2% (P<.01), respectively. SFA lesion
      location, long lesion length, and CTO were associated with the use of stents.
      Advanced Rutherford class was associated with a non-stent treatment strategy.
      CONCLUSION: The majority of endovascular peripheral arterial interventions are
      performed in the SFA; most include a CTO and in patients with diabetes mellitus.
      Operators use stents to primarily treat complex SFA lesions with overall similar
      outcomes, except for fewer amputations compared to a non-stent strategy.

PMID- 25589696
TI  - Automated carbon dioxide digital angiography for lower-limb arterial disease
      evaluation: safety assessment and comparison with standard iodinated contrast
      media angiography.
AB  - INTRODUCTION: Carbon dioxide (CO2) has been validated as a contrast agent in a
      large series of studies. A particular advantages of CO2 over iodinated contrast
      medium (ICM) is the absence of nephrotoxicity and allergic reactions. One of the
      limitations of CO2 angiography is the difficulty of CO2 manual injection due to
      its compressibility. The manual gas injection does not permit optimal control of
      the gas output. Development of an automated CO2 injector has overcome these
      problems. AIM: This study compares the feasibility, safety, and diagnostic
      accuracy of automated CO2 digital subtraction angiography (DSA) in comparison
      with ICM-DSA in the evaluation of critical limb ischemic (CLI) patients. METHODS:
      We performed DSA with both CO2 and ICM on 40 consecutive CLI patients and
      directly compared the two techniques. Sixteen females and 24 males participated
      in the study (mean age, 71.7 years). We assessed the diagnostic accuracy of CO2
      in identifying arterial stenosis in the lower limb, with ICM-DSA used as the gold
      standard. RESULTS: The overall diagnostic accuracy of CO2-DSA was 96.9%
      (sensitivity, 99.0%; specificity, 96.1%; positive predictive value, 91.1%;
      negative predictive value, 99.6%). Tolerable minor symptoms occurred in 3
      patients. No allergic reactions or significant decline in renal function were
      observed in patients receiving the CO2 injection. CONCLUSION: Carbon dioxide DSA
      is a valuable and safe alternative to traditional ICM-DSA for evaluating CLI
      patients. This modality should be considered as the standard choice for CLI
      patients undergoing angiographic evaluation who are known to have renal
      insufficiency or contrast allergy.

PMID- 25589698
TI  - The power of the story in an era of big data and huge databases.

PMID- 25589697
TI  - The utility of extension catheters in transradial percutaneous coronary
      intervention.
AB  - OBJECTIVES: To evaluate the use of extension catheters in transradial
      intervention of complex coronary lesions. BACKGROUND: Complex percutaneous
      coronary intervention (PCI) via transradial approach remains a challenge for many
      interventionalists, primarily due to the difficulty in obtaining adequate guide
      catheter support. METHODS: A retrospective case series identified 54 patients who
      presented for PCI of complex coronary lesions. A lesion was defined as complex if
      it contained severe calcification, proximal tortuosity, chronic total occlusion,
      or was located distal to a previously implanted stent. After identifying the
      complex lesions, a conversion to femoral approach was considered, but an attempt
      via the transradial approach with the use of an extension catheter was chosen as
      the initial strategy. Specific cases highlighting this approach are illustrated
      in detail. RESULTS: The average age of the patients was 72 years old, with male
      predominance (55%). The success rate of completing the transradial intervention
      with the help of an extension catheter was 96%. Stent delivery failed due to
      severe tortuosity and calcification in only 2 cases. The coronary artery involved
      was either the left anterior descending (n = 25), the left circumflex (n = 10),
      the right coronary artery (n = 14), or a saphenous vein graft (n = 5). There were
      no coronary dissections evident from use of the extension catheter. CONCLUSION:
      In the treatment of complex coronary lesions via the transradial approach, the
      use of an extension catheter may assist in improving successful intervention and
      decrease the frequency of crossover to a femoral approach.

PMID- 25589699
TI  - Transradial versus transfemoral intervention for the treatment of left main
      coronary bifurcations: results from the COBIS (COronary BIfurcation Stenting) II
      Registry.
AB  - OBJECTIVES: We compared clinical outcomes of transradial (TR) and transfemoral
      (TF) percutaneous coronary interventions (PCI) in patients with left main
      coronary artery (LMCA) bifurcation lesions. BACKGROUND: The use of TR approach is
      growing as an alternative to the routine use of the TF approach. However, there
      are limited data comparing the outcomes of these two approaches for the treatment
      of LMCA bifurcation lesions. METHODS: Between January 2003 and December 2009, a
      total of 853 patients undergoing PCI using drug-eluting stent (DES) implantation
      for LMCA bifurcation lesions were enrolled from 18 centers in Korea. We
      classified patients into the TR group (n = 212) and TF group (n = 641) according
      to the vascular approach. The primary outcome was major adverse cardiac event
      (MACE) rate, including composite of cardiac death, myocardial infarction (MI),
      and target lesion revascularization (TLR) in all patients and in 483 propensity
      score matched patients. RESULTS: There were no significant differences between TR
      and TF approaches for procedural success in the main vessel (98.6% vs. 99.7%;
      P=.07) and side branches (90.6% vs. 94.4%; P=.05). Thrombolysis in Myocardial
      Infarction major or minor bleeding occurred less frequently in the TR group than
      in the TF group (2.4% vs. 9.4%; P=.01). Over a median follow-up of 35 months,
      MACE rate did not significantly differ between TR and TF groups (9.9% vs. 14.5%;
      adjusted hazard ratio, 0.80; 95% confidence interval, 0.49-1.29; P=.36). These
      results were consistent after propensity-score matched analysis. CONCLUSIONS: TR
      PCI is a safe and effective vascular approach, even in patients with LMCA
      bifurcation lesions undergoing PCI with DES implantation.

PMID- 25589700
TI  - New-onset atrial fibrillation after surgical aortic valve replacement and
      transcatheter aortic valve implantation: a concise review.
AB  - Surgical aortic valve replacement (SAVR) and, more recently, transcatheter aortic
      valve implantation (TAVI) have been shown to be the only treatments that can
      improve the natural cause of severe aortic valve stenosis. However, after SAVR
      and TAVI, the incidence of new-onset atrial fibrillation (NOAF) is 31%-64% and 4%
      32%, respectively. NOAF is independently associated with adverse events such as
      stroke, death, and increased length of hospital stay. Increasing the knowledge of
      predisposing factors, optimal postprocedural monitoring, and prophylactic
      antiarrhythmic and antithrombotic therapy may reduce the risk of complications
      secondary to NOAF. 

PMID- 25589701
TI  - A short review of catheter-based superficial venous disease management: new
      directions, new paradigms.

PMID- 25589702
TI  - Lesion flow coefficient: a combined anatomical and functional parameter for
      detection of coronary artery disease--a clinical study.
AB  - Invasive diagnosis of coronary artery disease utilizes either anatomical or
      functional measurements. In this study, we tested a futuristic parameter, lesion
      flow coefficient (LFC, defined as the ratio of percent coronary area stenosis
      (%AS) to the square root of the ratio of the pressure drop across the stenosis to
      the dynamic pressure in the throat region), that combines both the anatomical
      (%AS) and functional measurements (pressure and flow) for application in a
      clinical setting. In 51 vessels, simultaneous pressure and flow readings were
      obtained using a 0.014" Combowire (Volcano Corporation). Anatomical details were
      assessed using quantitative coronary angiography (QCA). Fractional flow reserve
      (FFR), coronary flow reserve (CFR), hyperemic stenosis resistance index (HSR),
      and hyperemic microvascular index (HMR) were obtained at baseline and adenosine
      induced hyperemia. QCA data were corrected for the presence of guidewire and then
      the LFC values were calculated. LFC was correlated with FFR, CFR, HSR, and HMR,
      individually and in combination with %AS, under both baseline and hyperemic
      conditions. Further, in 5 vessels, LFC group mean values were compared between
      pre-PCI and post-PCI groups. P<.05 was considered statistically significant. LFC
      measured at hyperemia correlated significantly when the pressure-based FFR, flow
      based CFR, and anatomically measured %AS were combined (r = 0.64; P<.05).
      Similarly, LFC correlated significantly when HSR, HMR, and %AS were combined (r =
      0.72; P<.05). LFC was able to significantly distinguish between pre-PCI and post
      PCI groups (0.42 +/- 0.05 and 0.05 +/- 0.004, respectively; P<.05). Similar
      results were obtained for the LFC at baseline conditions. LFC, a futuristic
      parameter that combines both the anatomical and functional endpoints, has
      potential for application in a clinical setting for stenosis evaluation, under
      both hyperemic and baseline conditions. 

PMID- 25589703
TI  - Percutaneous closure of atrial septal defect in adults: very long-term clinical
      outcome and effects on aortic and mitral valve function.
AB  - AIM: To investigate the very long-term clinical outcomes of atrial septal defect
      (ASD) percutaneous closure in adult patients and to evaluate the 12-month effects
      of the device on aortic and mitral valve function. METHODS: Over a 12-year
      period, a total of 110 consecutive patients underwent percutaneous ASD closure. A
      yearly clinical follow-up was conducted and any adverse event was recorded. In a
      55-patient echocardiographic subgroup, the baseline and 12-month aortic and
      mitral regurgitation rate was recorded. RESULTS: Mean age was 50.9 +/- 17 years
      and 75% of patients were female. Mean ASD echocardiographic dimension was 17.6 +/
      6.2 mm (range, 5-36 mm). Procedural success rate was 97%. After a mean follow-up
      of 61.8 +/- 34.9 months (range, 6-167 months), all-cause death occurred in 2
      patients (1.8%) and the composite primary outcome of major adverse cardiovascular
      event (MACE) occurred in 5 patients (4.5%): 2 non-device related cardiac deaths
      occurred and 3 surgeries were required. The Kaplan-Meier analysis showed an event
      free survival at 140 months of 90%. In the 12-month echocardiographic substudy,
      no case of significant (moderate or severe) new-onset aortic regurgitation was
      detected, while 1 case (1.8%) of worsening mild-to-moderate aortic regurgitation
      was described (P=.90). No case of significant new-onset or worsening mitral
      regurgitation was noted. No patient needed aortic or mitral surgical repair at
      very long-term follow-up. CONCLUSIONS: Transcatheter ASD closure is a safe
      procedure with satisfactory very long-term clinical outcomes. The ASD device does
      not significantly affect aortic and mitral valve function.

PMID- 25589704
TI  - Subintimal TRAnscatheter Withdrawal (STRAW) of hematomas compressing the distal
      true lumen: a novel technique to facilitate distal reentry during recanalization
      of chronic total occlusion (CTO).
AB  - The development of a large hematoma impairing visualization of the distal true
      lumen is a recognized complication of antegrade recanalization of chronic total
      occlusions, often forcing the operator to abort the procedure or switch to a
      retrograde approach. We describe a novel technique utilizing an over-the-wire
      balloon inflated in the proximal occluded vessel to block inflow and allow
      aspiration of the blood from the subintimal space. This decompressed the true
      lumen, restored distal visualization, and allowed successful reentry using a
      dedicated technology. Utilization of this novel technique may rescue antegrade
      recanalization attempts complicated by large subintimal hematomas. 

PMID- 25589705
TI  - A case of an occlusive right coronary artery dissection after stent implantation:
      dilemmas and challenges.
AB  - A 53-year-old man with stable angina had a staged percutaneous coronary
      intervention to a critical focal stenosis of the mid-segment of the right
      coronary artery (RCA). Two hours after successful RCA stent implantation, the
      patient re-presented with inferior ST elevation secondary to acute dissection
      originating at the distal edge of the stent, causing subtotal occlusion of the
      distal RCA. The patient had TIMI-2 flow in the posterolateral branch and
      occlusion of the posterior descending artery. This case describes the procedural
      challenges the operators were faced with and successful use of the "rescue STAR"
      technique as a last resort. 

PMID- 25589706
TI  - Real-time three-dimensional intracardiac echocardiography: an early single-center
      experience.
AB  - As interventional procedures in structural heart diseases are coming of age,
      there is a significant lag in the periinterventional imaging development for
      these procedures to become safe, expedient, accurate, and well tolerated by this
      patient population. Currently, transesophageal echocardiography (TEE), including
      real-time three-dimensional (RT-3D), has been used for monitoring and guidance
      for these procedures. Accurate identification of the pathology, its anatomy, and
      its relationship with the adjoining structures along with spatial resolution is
      of paramount importance for wire and catheter placement, device deployment,
      evaluation of the results, and any potential complications. Two-dimensional
      intracardiac echocardiography (ICE) has been used extensively for a variety of
      interventional procedures that undergo conscious sedation of monitored
      anesthesia. RT-3D ICE has recently become available; we describe our initial
      experience with this new imaging technology. 

PMID- 25589708
TI  - [ApoE-containing HDL and the development of atherosclerosis].
AB  - The current state of knowledge about the role of high density lipoproteins (HDL)
      indicates that their anti-atherogenic function is mainly related to the
      effectiveness of their actions (mostly to the participation in reverse
      cholesterol transport from tissues to liver) rather than the concentration of HDL
      itself. HDLs are highly heterogeneous in their structure, lipid and protein
      composition and metabolic pathways and individual HDL subpopulations differ in
      their biological activity and effectiveness of anti-atherogenic actions.
      Apolipoproteins play a key role in HDL metabolism, therefore their presence in
      lipoproteins is one of the main criterion for HDL classification. According to
      this criterion HDLs containing apolipoprotein E, called HDL-apoE, are
      distinguished. Although the anti-atherogenic role of apo E has been demonstrated
      in many scientific reports, understanding of the mechanisms of formation,
      transformation and the role of HDL-apoE is still the aim of intense research. The
      results of epidemiological studies are inconclusive; some of them have
      demonstrated that high HDL- -apoE concentration has been associated with lower
      risk of developing coronary heart disease (CHD), while other studies have shown
      that high levels of HDL-apoE has been an independent risk factor for
      cardiovascular events and positively correlated with other risk factors for CHD. 

PMID- 25589709
TI  - [Antimicrobial peptides in asthma pathogenesis].
AB  - Antimicrobial peptides exhibit activity against bacteria, viruses, fungi, and
      parasites. They have been described not only as endogenous antibiotics but also
      as immune modulators with an impact on innate and adaptive immune functions.
      Asthma is one of the most common diseases, characterized by chronic airway
      inflammation, bronchial hyperreactivity and asthma attacks. Airway inflammation
      in asthma is characterized by allergic phenotypes, such as dense infiltration of
      eosinophils, mast cells, Th 2 lymphocytes and monocytes. Viral infections are
      often the cause of asthma exacerbation. This review highlights recent
      observations on the role of antimicrobial peptides in asthma pathogenesis. 

PMID- 25589710
TI  - [Amylin under examination. Fibrillogenic polypeptide of pancreatic amyloid].
AB  - In patients or animals affected by 2 type diabetes mellitus (diabetes mellitus
      type 2, DM2, non-insulin-dependent diabetes mellitus, NIDDM) or pancreatic tumor
      disease e.g., insulinoma, some pathological deposits, called amyloid, are
      observed among cells of islets of Langerhans. Among other constituents,
      pancreatic deposits consist of an insoluble, fibrillar form of peptide
      neurohormone termed amylin, produced by pancreatic beta cells. It is thought that
      formation of fibrillar deposits of misfolded and aggregated peptide is highly
      toxic to beta cells and leads to cell dysfunction, cell loss, pancreas
      destruction and progress of the disease. This relatively small, 37-amino acid
      peptide constitutes a serious scientific, research and to some extent a medical
      problem. This article presents amylin as a fibrillating molecule which
      participates in formation of amyloid deposits in human and animal pancreas,
      Langerhans islets as a microenvironment of pancreatic amyloid formation,
      occurrence of amylin and amyloid in animals and humans, and physico-chemical
      requirements to meet to name amylin deposit as amyloid. 

PMID- 25589707
TI  - Work and home stress: associations with anxiety and depression symptoms.
AB  - BACKGROUND: In the evolving work environment of global competition, the
      associations between work and home stress and psychological well-being are not
      well understood. AIMS: To examine the impact of psychosocial stress at work and
      at home on anxiety and depression. METHODS: In medically healthy employed men and
      women (aged 30-60), serial regression analyses were used to determine the
      independent association of psychosocial stress at work and at home with
      depression symptoms, measured using the Beck Depression Inventory-II (BDI-II),
      and anxiety symptoms, measured using the Spielberger Trait Anxiety Inventory
      (STAI). Psychosocial stress at work was measured using the Job Content
      Questionnaire to assess job psychological demands, job control, job social
      support and job insecurity. Psychosocial stress at home was assessed by 12
      questions including stress at home, personal problems, family demands and
      feelings about home life. RESULTS: Serial regression analyses in 129 subjects
      revealed that job insecurity and home stress were most strongly associated with
      depression and anxiety symptoms. Job insecurity accounted for 9% of the variation
      both in BDI-II scores and in STAI scores. Home stress accounted for 13 and 17% of
      the variation in BDI-II scores and STAI scores, respectively. In addition, job
      social support was significantly and independently associated with STAI scores
      but not BDI-II scores. CONCLUSIONS: Work and home stress were associated with
      anxiety and depression symptoms in both men and women. Both work and home stress
      should be considered in studies evaluating anxiety and depression in working
      populations.

PMID- 25589711
TI  - [The use of various diet supplements in metabolic syndrome].
AB  - Civilization development is associated with immense progress in science and
      significant improvement of human living conditions but simultaneously it
      contributes to many health problems including metabolic syndrome. Metabolic
      syndrome is a set of mutually associated factors including insulin resistance,
      hyperinsulinemia, obesity, lipids disorders and hypertension, which is the main
      cause of development of coronary heart disease and type 2 diabetes. The first
      line of defense against metabolic syndrome is a change of life style including
      body mass reduction, application of a low-calorie diet and performance of
      physical activity. In spite of the simplicity of therapy, long-term success of
      the above treatment among patients is observed seldom because it is very
      difficult to obey rigorous rules. Nowadays, it is considered that diet
      supplements including antioxidants, polyunsaturated fatty acids and mineral
      elements are helpful in metabolic syndrome treatment due to their antioxidant and
      anti-inflammatory properties. It is considered that a health balanced diet
      enriched with various diet supplements may be the best strategy in metabolic
      syndrome treatment. 

PMID- 25589712
TI  - [18 kDa translocator protein--implications in cell's functions].
AB  - The mitochondrial 18kDa Translocation Protein (TSPO) was first identified in 1977
      by its capability to bind benzodiazepines in peripheral tissues. It is more
      commonly known after its previous name - peripheral benzodiazepine receptor (PBR)
      as opposed to the central benzodiazepine receptor (CBR), from which it differs by
      location, structure and function. It is ubiquitous with highest expression in
      steroid-producing tissues, like adrenal cortex, ovaries, testicles, and placenta.
      The role of TSPO is crucial for living; its inactivation results in early
      embryonic-lethal phenotype in mice. TSPO has been implicated in various functions
      of cell, including steroidogenesis, cellular respiration, reactive oxygen species
      production, heme biosynthesis, immunomodulation, apoptosis, and cellular
      proliferation. TSPO has been shown to interact with other cellular proteins: 32
      kDa voltage-dependent anion channel (VDAC), 30 kDa adenine nucleotide translocase
      (ANT), cyclophilin D, hexokinase, creatinine kinase, diazepam binding inhibitor
      (DBI), phosphate carrier and Bcl-2 family. They are - involved in the formation
      and regulation of mitochondrial permeability transition pore (mPTP) at the
      junction of the inner and outer mitochondrial membranes. While the function and
      characteristics of the mPTP are known, its well defined, but its structure
      remains speculative. Changes in TSPO expression are associated with multiple
      disorders, including cancer, ischaemia-reperfusion injury, neurological diseases
      and psychiatric disorders, atheromatosis, and others. - TSPO is able to bind
      cholesterol, porphyrins and other ligands with different affinity. The current
      knowledge of TSPO implicates its potential use as a diagnostic marker and
      therapeutic target in different diseases and their therapies. 

PMID- 25589713
TI  - [Health--promoting effect of quercetin in human diet].
AB  - Quercetin is a plant flavonoid phytochemical exhibiting a broad spectrum of
      properties i.a. antioxidant, anti-inflammatory and immunomodulatory. However, the
      effect of quercetin is not clear. This compound at low concentrations can
      stimulate proliferation of human cells, so it can be a potential drug in the
      treatment of neurodegenerative diseases and in high concentrations, it induces
      apoptosis thereby eliminating the infected or abnormal cells and can serve as a
      potential anticancer drug with wide clinical application. Action of quercetin can
      be explained by its interference with cellular enzymes, receptors, transporters
      and signalling system. Due to its widespread occurrence in the plant world, it is
      an integral component of the human diet. The dietary quercetin occurs most often
      in the form of beta-glycosides connected mostly with rutinose, rhamnose and
      glucose. Depending on the nutritional habits, the daily intake of flavonoids,
      including quercetin, ranges from 3 to 70 mg. Epidemiological studies confirm an
      inverse correlation between the consumption of flavonoids and the incidence of
      lifestyle diseases and tumor formation. Published data indicate that consumption
      of foods rich in flavonoids reduces the risk of coronary heart disease. Thus,
      flavonoids - including quercetin - seem to be an interesting pro-health agent. 

PMID- 25589714
TI  - Amyloid-beta Modulates Both AbetaPP and Tau Phosphorylation.
AB  - Two histopathological hallmarks of Alzheimer's disease (AD), the tau rich
      neurofibrillary tangles and the senile plaques, predominating in amyloid-beta
      (Abeta), have fueled research in distinct directions. Evidence suggests that
      Abeta triggers imbalanced activities of protein phosphatases and kinases thus
      affecting the phosphorylation state of tau in AD. The amyloid-beta protein
      precursor (AbetaPP) itself appears to be hyperphosphorylated at different
      residues in AD brains, including at Thr668.The results reported in this
      manuscript show, for the first time, that Abeta(42) can impact upon the AbetaPP
      phosphorylation state at the Thr668 residue. This novel finding supports a
      putative model, whereby Abeta can modulate the phosphorylation state of AbetaPP
      regulating its processing and consequently its own production. Furthermore, the
      data presented shows that in primary cortical neurons, GSK3beta and Cdk5 are
      involved in AbetaPP phosphorylation at this residue and that PP1 and PP2B
      participate in AbetaPP dephosphorylation. Consistent with other reports, Abeta
      was reports, capable of increasing tau phosphorylation at the Ser396 and Ser262
      residues. This peptide is therefore a strong candidate for promoting the cross
      talk between signaling pathways, which simultaneously result in AbetaPP and tau
      hyperphosphorylation. In closing, the Abeta effect on protein kinases and protein
      phosphatases may constitute an alternative mechanism by which the peptide is able
      to modulate the phosphorylation state of both AbetaPP and tau in AD.

PMID- 25589715
TI  - Left temporal lobe epilepsy revealing left posterior cortical atrophy due to
      Alzheimer's disease.
AB  - Seizures can be an early symptom of Alzheimer's disease (AD) and can precede
      cognitive decline. Early epilepsy in AD can mimic transient epileptic amnesic
      syndrome (TEAS) or epileptic amnesic syndrome. We report the case of a patient
      who started a cerebrospinal fluid (CSF)-proven AD with partial seizures and TEAS
      that secondarily became a cortical posterior atrophy syndrome. CSF biomarkers
      showed a high amyloid production, amyloidopathy, and high level of total tau and
      p-Tau. This observation adds data to the complex AD-early epilepsy interactions
      and illustrates that atypical AD can cause a TEAS. Possible red flags for an
      underlying neurodegenerative process in TEAS are discussed. 

PMID- 25589716
TI  - Influence of oxidative stress biomarkers on cognitive decline.
AB  - BACKGROUND: Abnormal oxidative stress is an established feature of Alzheimer's
      disease (AD). Markers of lipoperoxidation and deficits in serum antioxidants
      could have a predictive value for identifying subjects at risk of dementia and to
      predict cognitive decline. OBJECTIVE: Search for relationships between the levels
      of some oxidative stress biomarkers and cognitive function decline that would
      help predict this decline. METHODS: The study solicited and included 97 patients
      aged 63 to 93 years with various suspected neurodegenerative diseases (35 with
      AD). They were followed up at six-month intervals over two years (2010-2012). The
      study: i) assessed the blood levels of glutathione peroxidase, glutathione, and
      malondialdehyde; ii) performed the Mini-Mental Status Examination (MMSE), the
      Clock Drawing test, the free/cued recall task with 16-item lists, the cue
      percentage; and the Trail Making Test; and iii) acquired brain magnetic resonance
      imaging or tomodensitometry. The primary outcome measure was the MMSE score.
      RESULTS: The MMSE score was correlated with the score of each neuropsychological
      test, the age at baseline, and the glutathione level. On average, the decline in
      the MMSE score was 1.63 points per six months. A 100 International Unit increase
      in glutathione peroxidase was associated with an average loss of 1.19 MMSE points
      per six months (p = 0.002). A 100 MUmol/L increase in glutathione was associated
      with an average loss of 1.80 MMSE points per six months (p = 0.014). CONCLUSION:
      Oxidative stress biomarkers, especially glutathione peroxidase and glutathione,
      may predict the course of cognitive decline in patients with AD or other
      neurodegenerative disorders.

PMID- 25589717
TI  - Plasma Complement factor H in Alzheimer's Disease.
AB  - Biomarkers for Alzheimer's disease (AD) should meet several criteria, including
      simplicity of testing. Inappropriate activation of the complement cascade has
      been implicated in the pathogenesis of AD. Complement factor H (CFH) is a
      regulator of the cascade, but studies on plasma CFH levels in AD have provided
      mixed results. This study compared plasma CFH levels in 317 AD cases with 254
      controls using an immunodiffusion assay. The sample had an 80% power to detect a
      difference of 23 mg/L between cases and controls, but no difference was evident.
      Plasma CFH may not be a suitable biomarker for AD. 

PMID- 25589718
TI  - Inhibition of Protein Phosphatase-2A (PP2A) by I1PP2A Leads to
      Hyperphosphorylation of Tau, Neurodegeneration, and Cognitive Impairment in Rats.
AB  - Protein phosphatase-2A (PP2A) deficiency is a cause of the abnormal
      hyperphosphorylation of tau, which composes neurofibrillary tangles (NFTs) in
      Alzheimer's disease (AD) brain. We previously reported that both mRNA and protein
      expression of inhibitor I of PP2A (I(1)(PP2A)) are elevated in AD brain and that
      this inhibitor induces a dose-dependent inhibition of PP2A activity and tau
      hyperphosphorylation in NIH3T3 cells. However, whether I(1)(PP2A) can induce AD
      neurofibrillary degeneration and cognitive impairment was not known. In the
      present study, we infected the brains of rat pups within 24 hours of birth with
      adeno-associated virus serotype 1 (AAV1) carrying I(1)(PP2A). In the adult AAV1
      I(1)(PP2A) rats, we found a decrease in PP2A activity and abnormal
      hyperphosphorylation of tau in the brain. Immunohistochemistry showed a
      significant reduction of MAP2 and synapsin 1 in AAV1- I(1)(PP2A) animals,
      suggesting that I(1)(PP2A) can induce a loss of dendritic and synaptic plasticity
      markers. Behavioral tests revealed that infection with AAV1- I(1)(PP2A) induced
      deficits in exploratory activity, spatial reference memory, and memory
      consolidation in adult rats. These studies suggest that I(1)(PP2A) can inhibit
      PP2A activity, and in turn induce AD neurofibrillary degeneration and cognitive
      deficits in rats.

PMID- 25589719
TI  - A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition
      and Mood in Alzheimer's Disease.
AB  - BACKGROUND: Increasing evidence points toward the efficacy of nutritional
      modifications in delaying cognitive decline and mood/behavioral difficulties in
      Alzheimer's disease (AD). Nutritional supplementation with individual agents has
      shown varied results suggesting the need for combinatorial intervention.
      OBJECTIVE: We set out to determine whether nutritional intervention could
      positively impact cognitive performance and behavioral difficulties for
      individuals diagnosed with AD. METHODS: A double-blind, multi-site, phase II
      study (ClinicalTrials.gov NCT01320527; Alzheimer's Association Trialmatch) was
      conducted in which 106 individuals with AD were randomized to a nutraceutical
      formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl
      cysteine, acetyl-L-carnitine) or placebo for 3 or 6 months, followed by an open
      label extension where participants received NF for 6 additional months. RESULTS:
      The NF cohort improved versus the placebo cohort within 3 months (Clox-1 p =
      0.0083, 95%CI [0.4481, 2.9343]; Dementia Rating Scale p = 0.0266, 95%CI [0.1722,
      2.7171]). Caregivers reported non-significant improvements in Neuropsychiatric
      Inventory. Both cohorts improved or maintained baseline performance during open
      label extensions. Activities of Daily Living did not change for either cohort.
      CONCLUSIONS: These findings extend phase I studies where NF maintained or
      improved cognitive performance and mood/behavior.

PMID- 25589720
TI  - Neuroprotective effects of hydrated fullerene C60: cortical and hippocampal EEG
      interplay in an amyloid-infused rat model of Alzheimer's disease.
AB  - We studied the effects of fullerene C60 nanoparticles, namely hydrated fullerene
      C60 (C60HyFn), on interrelations between EEG frequency spectra from the frontal
      cortex and the dorsal hippocampus (CA1) on an amyloid-beta (Abeta) rat model of
      Alzheimer's disease (AD). Infusion of Abeta1-42 protein (1.5 MUl) into the CA1
      region two weeks before EEG testing diminished hippocampal theta (3.8-8.4 Hz)
      predominance and eliminated cortical beta (12.9-26.2 Hz) predominance observed in
      baseline EEG of rats infused with saline (control) or with C60HyFn alone. In
      contrast, these Abeta1-42 effects were abolished in rats pretreated with C60HyFn,
      30 min apart. Dopaminergic mediation in AD has been shown to be involved in
      neuronal plasticity and Abeta transformation in different ways. To clarify its
      role in the cortex-hippocampus interplay in the Abeta model of AD, we used
      peripheral injection of a dopamine agonist, apomorphine (APO), at a low dose (0.1
      mg/kg). In rats infused with C60HyFn or Abeta1-42 alone, APO attenuated the
      cortical beta predominance, with immediate and delayed phases evident in the
      Abeta1-42-rats. Pretreatment with C60HyFn diminished the APO effect in the Abeta1
      42-treated rats. Thus, we show that intrahippocampal injection of Abeta1-42
      dramatically disrupts cortical versus hippocampal EEG interrelations and that
      pretreatment with the fullerene eliminates this abnormality. We suggest that some
      effects of C60HyFn may be mediated through presynaptic dopamine receptors and
      that water-soluble C60 fullerenes have a neuroprotective potential. 

PMID- 25589722
TI  - Localization and Trafficking of Amyloid-beta Protein Precursor and Secretases:
      Impact on Alzheimer's Disease.
AB  - Alzheimer's disease (AD) affects almost 35 million people worldwide. One of the
      neuropathological features of AD is the presence of extracellular amyloid
      plaques, which are mainly composed of amyloid-beta (Abeta) peptides. These
      peptides derive from the amyloidogenic proteolytic processing of the amyloid-beta
      protein precursor (AbetaPP), through the sequential action of beta- and gamma
      secretases. However, AbetaPP can also be cleaved by a non-amyloidogenic pathway,
      involving an alpha-secretase, and in this case the Abeta formation is precluded.
      The production of Abeta and of other AbetaPP catabolites depends on the spatial
      and temporal co-localization of AbetaPP with alpha- or beta-secretases and gamma
      secretase, which traffic through the secretory pathway in a highly regulated
      manner. Disturbances on AbetaPP and secretases intracellular trafficking and,
      consequently, in their localization may affect dynamic interactions between these
      proteins with consequences in the AD pathogenesis. In this article, we critically
      review the recent knowledge about the trafficking and co-localization of AbetaPP
      and related secretases in the brain under physiological and AD conditions. A
      particular focus is given to data concerning the distribution of AbetaPP and
      secretases in different types of synapses relatively to other neuronal or glial
      localizations. Furthermore, we discuss some possible signals that govern the
      dynamic encounter of AbetaPP with each group of secretases, such as AbetaPP
      mutations, estrogen deprivation, chronic stress, metabolic impairment, and
      alterations in sleep pattern-associated with aging. The knowledge of key signals
      that are responsible for the shifting of AbetaPP processing away from alpha
      secretases and toward the beta-secretases might be useful to develop AD
      therapeutic strategies. 

PMID- 25589721
TI  - Calcium signaling, excitability, and synaptic plasticity defects in a mouse model
      of Alzheimer's disease.
AB  - Alzheimer's disease (AD) and aging result in impaired ability to store memories,
      but the cellular mechanisms responsible for these defects are poorly understood.
      Presenilin 1 (PS1) mutations are responsible for many early-onset familial AD
      (FAD) cases. The phenomenon of hippocampal long-term potentiation (LTP) is widely
      used in studies of memory formation and storage. Recent data revealed long-term
      LTP maintenance (L-LTP) is impaired in PS1-M146V knock-in (KI) FAD mice. To
      understand the basis for this phenomenon, in the present study we analyzed
      structural synaptic plasticity in hippocampal cultures from wild type (WT) and KI
      mice. We discovered that exposure to picrotoxin induces formation of mushroom
      spines in both WT and KI cultures, but the maintenance of mushroom spines is
      impaired in KI neurons. This maintenance defect can be explained by an abnormal
      firing pattern during the consolidation phase of structural plasticity in KI
      neurons. Reduced frequency of neuronal firing in KI neurons is caused by enhanced
      calcium-induced calcium release (CICR), enhanced activity of calcium-activated
      potassium channels, and increased afterhyperpolarization. As a result,
      "consolidation" pattern of neuronal activity converted to "depotentiation"
      pattern of neuronal activity in KI neurons. Consistent with this model, we
      demonstrated that pharmacological inhibitors of CICR (dantrolene), of calcium
      activated potassium channels (apamin), and of calcium-dependent phosphatase
      calcineurin (FK506) are able to rescue structural plasticity defects in KI
      neurons. Furthermore, we demonstrate that incubation with dantrolene or apamin
      also rescued L-LTP defects in KI hippocampal slices, suggesting a role for a
      similar mechanism. This proposed mechanism may be responsible for memory defects
      in AD but also for age-related memory decline. 

PMID- 25589724
TI  - Clinical and Neuropsychological  Comparisons of Early-Onset Versus  Late-Onset
      Frontotemporal Dementia:  A CREDOS-FTD Study.
AB  - BACKGROUND: Cognitive performance changes with chronological aging. Previous
      studies investigating clinical heterogeneity in frontotemporal dementia (FTD)
      according to the age of symptom onset did not consider the effect of
      chronological aging on cognition. OBJECTIVE: We compared cognitive and behavioral
      symptoms in patients with early-onset (EO) and late-onset (LO) FTD with
      consideration of chronological aging effect. METHODS: A total of 166 FTD patients
      were enrolled consecutively from multi-center memory clinics using a nationwide
      FTD register. To control for the effects of chronological aging on
      neuropsychological scores, seven hundred and two subjects with normal cognition
      were also enrolled and regression models were set up. Neuropsychological scores
      that were detrended with the regression models and the behavioral symptoms of the
      EO-FTD and LO-FTD groups were compared. Subgroup analyses were performed for
      three main subtypes of FTD, behavioral variant frontotemporal dementia (bvFTD),
      semantic dementia (SD), and progressive non-fluent aphasia (PNFA). RESULTS: Among
      166 FTD patients, there were 76 bvFTD, 57 SD, and 33 PNFA patients who met new
      diagnostic criteria for bvFTD or primary progressive aphasia, respectively. LO
      FTD (48.2%) was more common than previously thought and the proportions of EO and
      LO groups differed across FTD subtypes. EO-FTD patients had lower memory and
      frontal/executive scores and more prominent frontal/behavioral symptoms than LO
      FTD patients. CONCLUSION: Our study suggested that FTD could be heterogeneous
      with respect the age of symptom onset. After controlling for the effects of
      chronological aging, EO-FTD patients exhibited more profound memory and
      frontal/executive dysfunction and more behavioral symptoms than LO-FTD patients.

PMID- 25589723
TI  - Prediction of Outcomes in Mild Cognitive  Impairment by Using 18F-FDG-PET:  A
      Multicenter Study.
AB  - BACKGROUND: 18F-FDG-PET is defined as a biomarker of neuronal injury according to
      the revised National Institute on Aging-Alzheimer's Association criteria.
      OBJECTIVE: The objective of this multicenter prospective cohort study was to
      examine the value of 18F-FDG-PET in predicting the development of Alzheimer's
      disease (AD) in patients with mild cognitive impairment (MCI). METHODS: In total,
      114 patients with MCI at 9 participating institutions underwent clinical and
      neuropsychological examinations, MRI, and 18F-FDG-PET at baseline. The cases were
      visually classified into predefined dementia patterns by three experts.
      Anautomated analysis for 18F-FDG-PET was also performed to calculate the PET
      score. Subjects were followed periodically for 3 years, and progression to
      dementia was evaluated. RESULTS: In 47% of the patients with MCI, progression of
      symptoms justified the clinical diagnosis of "probable AD". The PET visual
      interpretation predicted conversion to AD during 3-year follow-up with an overall
      diagnostic accuracy of 68%. Overall diagnostic accuracy of the PET score was
      better than that of PET visual interpretation at all follow-up intervals, and the
      optimized PET score threshold revealed the best performance at the 2-year follow
      up interval with an overall diagnostic accuracy of 83%,a sensitivity of 70%, and
      a specificity of 90%. Multivariate logistic regression analysis identified the
      PET score as the most significant predictive factor distinguishing AD converters
      from non-converters. CONCLUSION: The PET score is the most statistically
      significant predictive factor for conversion from MCI to AD, and the diagnostic
      performance of the PET score is more promising for rapid converters over 2 years.

PMID- 25589725
TI  - Impairment of age estimation from faces in Alzheimer's disease.
AB  - A prerequisite for any function in social cognition is the perception and
      processing of social cues. Age estimation is a skill that is used in everyday
      life and is fundamental in social interactions. This study evaluated whether
      facial age estimation is impaired in patients with mild to moderate Alzheimer's
      disease (AD). The current age of faces is known to have an impact on age
      estimation, and therefore stimuli belonging to different age groups (young,
      middle-aged, and older adults' faces) were used. As expected, an impairment of
      age estimation from faces was observed in mild to moderate AD patients. However,
      the profile of impairment depended on the age of faces and stage of the disease.
      Mild AD patients presented difficulties mainly in assessing the age of middle
      aged adults. In moderate disease stage, these difficulties also affected the age
      estimation of young adult faces. Interestingly, AD patients remained relatively
      good at estimating the age of older adults' faces, compared to healthy controls. 

PMID- 25589726
TI  - Structural and regulatory elements of the interaction between amyloid-beta
      protein precursor and Homer3.
AB  - Amyloid-beta protein precursor (AbetaPP) metabolism and the accumulation of its
      derivative amyloid-beta (Abeta) peptide in senile plaques have been considered
      key players in the development of Alzheimer's disease (AD). However, the
      mechanisms underlying the generation and the deposition of Abeta are not clear
      but emphasis has been given in the role of AbetaPP protein interactions that
      regulate its processing and offer a means to manipulate Abeta production. We have
      previously shown that AbetaPP interacts with members of the Homer protein family,
      which leads to inhibition of Abeta generation. Herein, we studied the structural
      parameters of AbetaPP/Homer3 interaction by analyzing the sequences and domains
      that play a role in the formation of the complex. We found that the cytoplasmic
      tail of AbetaPP is necessary for the interaction. Regarding Homer3, we report
      that both the EVH1 protein interacting domain and the polymerization coiled coil
      domain are essential for the complex assembly. Importantly, phosphorylation of
      Homers at certain serine residues seems to enhance the interaction with AbetaPP,
      possibly underlying our recent work suggesting that calcium signaling also
      regulates the interaction. Our results show that the regulation of AbetaPP/Homer3
      interaction might be critical in the context of Alzheimer's disease pathology as
      a novel target for regulating AbetaPP function and metabolism. 

PMID- 25589727
TI  - Different Patterns of Theory of Mind Impairment in Mild Cognitive Impairment.
AB  - Theory of Mind refers to the ability to infer other's mental states, their
      beliefs, intentions, or knowledge. To date, only two studies have reported the
      presence of Theory of Mind impairment in mild cognitive impairment (MCI). In the
      present study,we evaluated 20 MCI patients and compared them with 25 healthy
      control participants using two Theory of Mind tasks. The first task was a false
      belief paradigm as frequently used in the literature, and the second one was a
      referential communication task,assessing Theory of Mind in a real situation of
      interaction and which had never been used before in this population. The results
      showed that MCI patients presented difficulties inferring another person's
      beliefs about reality and attributing knowledge to them in a situation of real
      life interaction. Two different patterns of Theory of Mind emerged among the
      patients. In comparison with the control group, some MCI patients demonstrated
      impairment only in the interaction task and presented isolated episodicmemory
      impairment, while others were impaired in both Theory of Mind tasks and presented
      cognitive impairment impacting both episodic memory and executive functioning.
      Theory of Mind is thus altered in the very early stages of cognitive impairment
      even in real social interaction, which could impact precociously relationships in
      daily life.

PMID- 25589728
TI  - Predictive factors of clinical response to cholinesterase inhibitors in mild and
      moderate Alzheimer's disease and mixed dementia: a one-year naturalistic study.
AB  - BACKGROUND: Naturalistic studies evaluate individuals in their usual way of
      living, presenting more "real-life" data regarding patients and their diseases.
      OBJECTIVE: To investigate demographic, clinical, and genetic factors that could
      be predictive of good response to cholinesterase inhibitors (ChEI) treatment in
      Alzheimer's disease (AD) and AD + cerebrovascular disease (CVD). PATIENTS AND
      METHODS: A total of 129 patients were diagnosed with AD or AD + CVD and with mild
      to-moderate dementia. After a 12-month treatment, 97 patients completed the
      study. They were evaluated at baseline and after three, six, and 12 months of
      ChEI (donepezil or rivastigmine or galantamine) use. APOE genotype and CYP2D6
      polymorphisms were determined for all of the participants. In each visit, we used
      cognitive, functional, mood, and behavior scales. We classified patients
      according to their scores in the Mini-Mental State Examination (MMSE). Good
      responders were defined as those scoring >=2 in the MMSE at 12 months. RESULTS:
      The rate of good clinical response was 27.8%. In a longitudinal analysis, the
      patients with mild AD and also good responders at three months were considered to
      be good responders at 12 months. There was no correlation between ChEI dose, APOE
      and CYP2D6 polymorphisms, and the pattern of clinical response. CONCLUSION: A
      higher rate of good response was observed in this study compared to that in
      previous investigations. The pharmacogenetic aspects do not seem to have an
      influence in the response.

PMID- 25589730
TI  - Mechanisms of molecular mimicry involving the microbiota in neurodegeneration.
AB  - The concept of molecular mimicry was established to explain commonalities of
      structure which developed in response to evolutionary pressures. Most examples of
      molecular mimicry in medicine have involved homologies of primary protein
      structure which cause disease. Molecular mimicry can be expanded beyond amino
      acid sequence to include microRNA and proteomic effects which are either
      pathogenic or salutogenic (beneficial) in regard to Parkinson's disease,
      Alzheimer's disease, and related disorders. Viruses of animal or plant origin may
      mimic nucleotide sequences of microRNAs and influence protein expression. Both
      Parkinson's and Alzheimer's diseases involve the formation of transmissible self
      propagating prion-like proteins. However, the initiating factors responsible for
      creation of these misfolded nucleating factors are unknown. Amyloid patterns of
      protein folding are highly conserved through evolution and are widely distributed
      in the world. Similarities of tertiary protein structure may be involved in the
      creation of these prion-like agents through molecular mimicry. Cross-seeding of
      amyloid misfolding, altered proteostasis, and oxidative stress may be induced by
      amyloid proteins residing in bacteria in our microbiota in the gut and in the
      diet. Pathways of molecular mimicry induced processes induced by bacterial
      amyloid in neurodegeneration may involve TLR 2/1, CD14, and NFkappaB, among
      others. Furthermore, priming of the innate immune system by the microbiota may
      enhance the inflammatory response to cerebral amyloids (such as amyloid-beta and
      alpha-synuclein). This paper describes the specific molecular pathways of these
      cross-seeding and neuroinflammatory processes. Evolutionary conservation of
      proteins provides the opportunity for conserved sequences and structures to
      influence neurological disease through molecular mimicry. 

PMID- 25589731
TI  - Serum miR-206 and miR-132 as Potential Circulating Biomarkers for Mild Cognitive
      Impairment.
AB  - MicroRNAs (miRNAs), a class of small, non-coding RNA molecules with gene
      regulatory functions, have emerged to play a critical role in the pathogenesis of
      a variety of diseases. Recently, circulating miRNAs have been reported as
      potential biomarkers for various pathologic conditions. The present study was
      performed to investigate the potential role of circulating miRNAs as diagnostic
      biomarkers for mild cognitive impairment (MCI). We collected 66 patients with MCI
      and 76 normal controls from our previous cross-sectional cohort study. Seven
      miRNAs (miR-206, miR-132, miR-193b, miR-130b, miR-20a, miR-296, and miR-329)
      related to Alzheimer's disease (AD) were detected in serum using a quantitative
      real-time PCR (qRT-PCR) method. Each miRNA's diagnostic performance was evaluated
      by receiver operating characteristic curves and the areas under curves (AUC)
      analysis. The levels of miR-206 and miR-132 in MCI patients' serum were
      significantly elevated compared to normal controls. Combining detection of miR
      206 and miR-132 achieved the highest AUC of 0.981, followed by test of miR-206
      (AUC = 0.880) and miR-132 (AUC = 0.912) separately. Importantly, miR-206 and miR
      132 were respectively correlated with the Montreal Cognitive Assessment score in
      MCI patients. These results preliminarily indicated that circulating miR-206 and
      miR-132 as novel miRNAs upregulated in MCI patient were potential biomarkers for
      diagnosis of MCI. 

PMID- 25589729
TI  - Partial Loss of the Glutamate Transporter GLT-1 Alters Brain Akt and Insulin
      Signaling in a Mouse Model of Alzheimer's Disease.
AB  - The glutamate transporter GLT-1 (also called EAAT2 in humans) plays a critical
      role in regulating extracellular glutamate levels in the central nervous system
      (CNS). In Alzheimer's disease (AD), EAAT2 loss is associated with neuropathology
      and cognitive impairment. In keeping with this, we have reported that partial GLT
      1 loss (GLT-1+/-) causes early-occurring cognitive deficits in mice harboring
      familial AD AbetaPPswe/PS1DeltaE9 mutations. GLT-1 plays important roles in
      several molecular pathways that regulate brain metabolism, including Akt and
      insulin signaling in astrocytes. Significantly, AD pathogenesis also involves
      chronic Akt activation and reduced insulin signaling in the CNS. In this report
      we tested the hypothesis that GLT-1 heterozygosity (which reduces GLT-1 to levels
      that are comparable to losses in AD patients) in AbetaPPswe/PS1DeltaE9 mice would
      induce sustained activation of Akt and disturb components of the CNS insulin
      signaling cascade. We found that partial GLT-1 loss chronically increased Akt
      activation (reflected by increased phosphorylation at serine 473), impaired
      insulin signaling (reflected by decreased IRbeta phosphorylation of tyrosines
      1150/1151 and increased IRS-1 phosphorylation at serines 632/635 - denoted as
      636/639 in humans), and reduced insulin degrading enzyme (IDE) activity in brains
      of mice expressing familial AbetaPPswe/PS1DeltaE9 AD mutations. GLT-1 loss also
      caused an apparent compensatory increase in IDE activity in the liver, an organ
      that has been shown to regulate peripheral amyloid-beta levels and expresses GLT
      1. Taken together, these findings demonstrate that partial GLT-1 loss can cause
      insulin/Akt signaling abnormalities that are in keeping with those observed in
      AD. 

PMID- 25589732
TI  - Luteolin Reduces BACE1 Expression through NF-kappaB and through Estrogen Receptor
      Mediated Pathways in HEK293 and SH-SY5Y Cells.
AB  - Beta-secretase (BACE1) controls an essential step for the generation of amyloid-
      peptide (Abeta). As Abeta forms the principle pathologies in Alzheimer's disease,
      lowering A production by inhibiting BACE1 is a plausible therapeutic approach. In
      the present study, we identified a natural polyphenol, luteolin, as a potent
      inhibitor of BACE1 transcription inhuman embryonic kidney 293 (HEK293) and human
      neuroblastoma (SH-SY5Y) cell lines. Luteolin is capable of suppressing the
      activation of BACE1 promoter by NF-kappaB signaling. We further characterized
      that luteolin interferes with NF-kappaB signaling by with both directly and
      indirectly disrupting p65 complex formation. In addition, we discovered that
      estrogen receptor mediates luteolin's effect in inhibiting NF-kappaB signaling
      inhibiting and BACE1 transcription. Interestingly, the beneficial effects of
      luteolin may be attributed to selective activation profiles of luteolin to
      different estrogen receptor subtypes. Our study reports luteolin as a potent
      BACE1-inhibiting compound, providing useful information in understanding estrogen
      receptor- and NF-kappaB-mediated signaling and in regulating BACE1 expression.

PMID- 25589735
TI  - Salipiger nanhaiensis sp. nov., a bacterium isolated from deep sea water.
AB  - A Gram-stain-negative, facultatively anaerobic, chemoheterotrophic, moderately
      halophilic, exopolysaccharide (EPS)-producing, cream, non-motile and rod-shaped
      bacterium, designated strain ZH114(T), was isolated from deep water of the South
      China Sea, and was subjected to a polyphasic taxonomic study. Phylogenetic
      analysis, based on 16S rRNA gene sequences, indicated that this strain belongs to
      the genus Salipiger with the highest sequence similarity to Salipiger mucescens
      LMG 22090(T) (96.83%), followed by Pseudodonghicola xiamenensis LMG 24574(T)
      (96.12%). Growth occurred at 4-37  degrees C (optimum 32  degrees C), pH 6.0-10.0
      (optimum pH 9.0-10.0) and in the presence of 0-19% NaCl (w/v) (optimum 6%, w/v).
      It did not produce poly-beta-hydroxyalkanoate granules or bacteriochlorophyll a.
      Acid was produced from glycerol, erythrose, ribose, D-xylose, galactose, glucose,
      fructose, mannitol, cellobiose, maltose, lactose, melibiose, turanose, D-lyxose,
      D-tagatose, D-fucose, D-arabitol and L-arabitol after inoculating for 24 h and
      weakly positive results were also detected after 48 h in API 50CH strips with D
      arabinose, L-arabinose, L-xylose, adonitol, mannose, aesculin, salicin, sucrose,
      mycose and L-fucose. The predominant fatty acids were C(18 : 1)omega7c and/or
      C(18 : 1)omega6c, C(16 : 0), C(18 : 0) and 11-methyl C(18 : 1)omega7c. The major
      polar lipids of ZH114(T) were phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine and two unidentified lipids. The major respiratory
      quinone was ubiquinone Q-10. The genomic DNA G+C content of strain ZH114(T) was
      63.8 mol%. Based on this phenotypic, chemotaxonomic and phylogenetic analysis,
      strain ZH114(T) should be classified as a representative of a novel species of
      the genus Salipiger , for which the name Salipiger nanhaiensis sp. nov. is
      proposed. The type strain is ZH114(T) ( = JCM 19383(T) = KCTC 32468(T)).

PMID- 25589734
TI  - Sinomonas susongensis sp. nov., isolated from the surface of weathered biotite.
AB  - A novel actinomycete, designated strain A31(T), was isolated from the surface of
      weathered biotite in Susong, Anhui Province, China. The organism grew optimally
      at 30  degrees C, at pH 8.0 and with 1% (w/v) NaCl. Strain A31(T) had A3alpha as
      the cell-wall peptidoglycan type and galactose, mannose and rhamnose as whole
      cell sugars. Anteiso-C(15 : 0) and anteiso-C(17 : 0) were the major cellular
      fatty acids and MK-9(H2) was the predominant respiratory quinone. In addition,
      the total polar lipids were diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylinositol, phosphatidylmonomethylethanolamine and four glycolipids.
      The genomic DNA G+C content of strain A31(T) was 70.8 mol%. Phylogenetic analysis
      based on 16S rRNA gene sequences showed that strain A31(T) was related most
      closely to Sinomonas albida LC13(T) (98.3% similarity), Sinomonas atrocyanea DSM
      20127(T) (98.2%), Sinomonas soli CW 59(T) (98.1%), Sinomonas flava CW 108(T)
      (97.8%), 'Sinomonas mesophila' MPKL 26 (97.3%), Sinomonas echigonensis LC10(T)
      (97.1%) and ' Sinomonas notoginsengisoli ' SYP-B575 (96.7%). DNA-DNA
      hybridization studies with the new isolate showed relatedness values of 16.0
      56.6% with its six closest neighbours. Based on phenotypic, chemotaxonomic and
      phylogenetic analysis, strain A31(T) represents a novel species of the genus
      Sinomonas , for which the name Sinomonas susongensis sp. nov. is proposed. The
      type strain is A31(T) ( = DSM 28245(T) = CCTCC AB 2014068(T)).

PMID- 25589736
TI  - Response to Tindall (2014) on the legitimacy of the names Solimonadaceae Losey et
      al. 2013, Xanthomonadaceae Saddler and Bradbury 2005 and Xanthomonadales Saddler
      and Bradbury 2005.

PMID- 25589737
TI  - Jiella aquimaris gen. nov., sp. nov., isolated from offshore surface seawater.
AB  - A Gram-stain-negative, strictly aerobic and rod-shaped motile bacterium with
      peritrichous flagella, designated strain LZB041(T), was isolated from offshore
      surface seawater of the East China Sea. Phylogenetic analysis based on 16S rRNA
      gene sequences indicated that strain LZB041(T) formed a lineage within the family
      ' Aurantimonadaceae' that was distinct from the most closely related genera
      Aurantimonas (96.0-96.4% 16S rRNA gene sequence similarity) and Aureimonas (94.5
      96.0%). Optimal growth occurred in the presence of 1-7% (w/v) NaCl, at pH 7.0-8.0
      and at 28-37  degrees C. Ubiquinone-10 was the predominant respiratory quinone.
      The major fatty acids (>10% of total fatty acids) were C(18 : 1)omega7c and/or
      C(18 : 1)omega6c (summed feature 8) and cyclo-C(19 : 0)omega8c. The major polar
      lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylmonomethylethanolamine, one unknown
      aminolipid, one unknown phospholipid and one unknown polar lipid. The DNA G+C
      content of strain LZB041(T) was 71.3 mol%. On the basis of polyphasic analysis,
      strain LZB041(T) is considered to represent a novel species of a new genus in the
      class Alphaproteobacteria , for which the name Jiella aquimaris gen. nov., sp.
      nov. is proposed. The type strain of the type species is LZB041(T) ( = JCM
      30119(T) = MCCC 1K00255(T)).

PMID- 25589739
TI  - Guidance of movements by prior experience: a Bayesian account of reach
      performance.

PMID- 25589738
TI  - A new method for estimating species age supports the coexistence of malaria
      parasites and their Mammalian hosts.
AB  - Species in the genus Plasmodium cause malaria in humans and infect a variety of
      mammals and other vertebrates. Currently, estimated ages for several mammalian
      Plasmodium parasites differ by as much as one order of magnitude, an inaccuracy
      that frustrates reliable estimation of evolutionary rates of disease-related
      traits. We developed a novel statistical approach to dating the relative age of
      evolutionary lineages, based on Total Least Squares regression. We validated this
      lineage dating approach by applying it to the genus Drosophila. Using data from
      the Drosophila 12 Genomes project, our approach accurately reconstructs the age
      of well-established Drosophila clades, including the speciation event that led to
      the subgenera Drosophila and Sophophora, and age of the melanogaster species
      subgroup. We applied this approach to hundreds of loci from seven mammalian
      Plasmodium species. We demonstrate the existence of a molecular clock specific to
      individual Plasmodium proteins, and estimate the relative age of mammalian
      infecting Plasmodium. These analyses indicate that: 1) the split between the
      human parasite Plasmodium vivax and P. knowlesi, from Old World monkeys, occurred
      6.1 times earlier than that between P. falciparum and P. reichenowi, parasites of
      humans and chimpanzees, respectively; and 2) mammalian Plasmodium parasites
      originated 22 times earlier than the split between P. falciparum and P.
      reichenowi. Calibrating the absolute divergence times for Plasmodium with
      eukaryotic substitution rates, we show that the split between P. falciparum and
      P. reichenowi occurred 3.0-5.5 Ma, and that mammalian Plasmodium parasites
      originated over 64 Ma. Our results indicate that mammalian-infecting Plasmodium
      evolved contemporaneously with their hosts, with little evidence for parasite
      host-switching on an evolutionary scale, and provide a solid timeframe within
      which to place the evolution of new Plasmodium species. 

PMID- 25589740
TI  - The palmitoyl acyltransferase DHHC2 regulates recycling endosome exocytosis and
      synaptic potentiation through palmitoylation of AKAP79/150.
AB  - Phosphorylation and dephosphorylation of AMPA-type ionotropic glutamate receptors
      (AMPARs) by kinases and phosphatases and interactions with scaffold proteins play
      essential roles in regulating channel biophysical properties and trafficking
      events that control synaptic strength during NMDA receptor-dependent synaptic
      plasticity, such as LTP and LTD. We previously demonstrated that palmitoylation
      of the AMPAR-linked scaffold protein A-kinase anchoring protein (AKAP) 79/150 is
      required for its targeting to recycling endosomes in dendrites, where it
      regulates exocytosis from these compartments that is required for LTP-stimulated
      enlargement of postsynaptic dendritic spines, delivery of AMPARs to the plasma
      membrane, and maintenance of synaptic potentiation. Here, we report that the
      recycling endosome-resident palmitoyl acyltransferase DHHC2 interacts with and
      palmitoylates AKAP79/150 to regulate these plasticity signaling mechanisms. In
      particular, RNAi-mediated knockdown of DHHC2 expression in rat hippocampal
      neurons disrupted stimulation of exocytosis from recycling endosomes, enlargement
      of dendritic spines, AKAP recruitment to spines, and potentiation of AMPAR
      mediated synaptic currents that occur during LTP. Importantly, expression of a
      palmitoylation-independent lipidated AKAP mutant in DHHC2-deficient neurons
      largely restored normal plasticity regulation. Thus, we conclude that DHHC2
      AKAP79/150 signaling is an essential regulator of dendritic recycling endosome
      exocytosis that controls both structural and functional plasticity at excitatory
      synapses. 

PMID- 25589741
TI  - Neuropathic pain is constitutively suppressed in early life by anti-inflammatory
      neuroimmune regulation.
AB  - Peripheral nerve injury can trigger neuropathic pain in adults but not in
      infants; indeed, for unknown reasons, neuropathic pain is rare before
      adolescence. We show here that the absence of neuropathic pain response in infant
      male rats and mice following nerve injury is due to an active, constitutive
      immune suppression of dorsal horn pain activity. In contrast to adult nerve
      injury, which triggers a proinflammatory immune response in the spinal dorsal
      horn, infant nerve injury triggers an anti-inflammatory immune response,
      characterized by significant increases in IL-4 and IL-10. This immediate anti
      inflammatory response can also be evoked by direct C-fiber nerve stimulation in
      infant, but not adult, mice. Blockade of the anti-inflammatory activity with
      intrathecal anti-IL10 unmasks neuropathic pain behavior in infant nerve injured
      mice, showing that pain hypersensitivity in young mice is actively suppressed by
      a dominant anti-inflammatory neuroimmune response. As infant nerve injured mice
      reach adolescence (postnatal day 25-30), the dorsal horn immune profile switches
      from an anti-inflammatory to a proinflammatory response characterized by
      significant increases in TNF and BDNF, and this is accompanied by a late onset
      neuropathic pain behavior and increased dorsal horn cell sensitivity to cutaneous
      mechanical and cold stimuli. These findings show that neuropathic pain following
      early life nerve injury is not absent but suppressed by neuroimmune activity and
      that "latent" pain can still emerge at adolescence, when the neuroimmune profile
      changes. The data may explain why neuropathic pain is rare in young children and
      also why it can emerge, for no observable reason, in adolescent patients. 

PMID- 25589742
TI  - Necessary, yet dissociable contributions of the insular and ventromedial
      prefrontal cortices to norm adaptation: computational and lesion evidence in
      humans.
AB  - Social norms and their enforcement are fundamental to human societies. The
      ability to detect deviations from norms and to adapt to norms in a changing
      environment is therefore important to individuals' normal social functioning.
      Previous neuroimaging studies have highlighted the involvement of the insular and
      ventromedial prefrontal (vmPFC) cortices in representing norms. However, the
      necessity and dissociability of their involvement remain unclear. Using model
      based computational modeling and neuropsychological lesion approaches, we
      examined the contributions of the insula and vmPFC to norm adaptation in seven
      human patients with focal insula lesions and six patients with focal vmPFC
      lesions, in comparison with forty neurologically intact controls and six brain
      damaged controls. There were three computational signals of interest as
      participants played a fairness game (ultimatum game): sensitivity to the fairness
      of offers, sensitivity to deviations from expected norms, and the speed at which
      people adapt to norms. Significant group differences were assessed using
      bootstrapping methods. Patients with insula lesions displayed abnormally low
      adaptation speed to norms, yet detected norm violations with greater sensitivity
      than controls. Patients with vmPFC lesions did not have such abnormalities, but
      displayed reduced sensitivity to fairness and were more likely to accept the most
      unfair offers. These findings provide compelling computational and lesion
      evidence supporting the necessary, yet dissociable roles of the insula and vmPFC
      in norm adaptation in humans: the insula is critical for learning to adapt when
      reality deviates from norm expectations, and that the vmPFC is important for
      valuation of fairness during social exchange. 

PMID- 25589743
TI  - Leptin receptor signaling in the hypothalamus regulates hepatic autonomic nerve
      activity via phosphatidylinositol 3-kinase and AMP-activated protein kinase.
AB  - Leptin action in the brain has emerged as an important regulator of liver
      function independently from its effects on food intake and body weight. The
      autonomic nervous system plays a key role in the regulation of physiological
      processes by leptin. Here, we used direct recording of nerve activity from
      sympathetic or vagal nerves subserving the liver to investigate how brain action
      of leptin controls hepatic autonomic nerve activity. Intracerebroventricular
      (ICV) administration of leptin activated hepatic sympathetic traffic in rats and
      mice in dose- and receptor-dependent manners. The hepatic sympatho-excitatory
      effects of leptin were also observed when leptin was microinjected directly into
      the arcuate nucleus (ARC), but not into the ventromedial hypothalamus (VMH).
      Moreover, using pharmacological and genetic approaches, we show that leptin
      induced increase in hepatic sympathetic outflow depends on PI3K but not AMP
      activated protein kinase (AMPK), STAT3, or ERK1/2. Interestingly, ICV leptin also
      increased hepatic vagal nerve activity in rats. We show that this response is
      reproduced by intra-ARC, but not intra-VMH, leptin administration and requires
      PI3K and AMPK. We conclude that central leptin signaling conveys the information
      to the liver through the sympathetic and parasympathetic branches of the
      autonomic nervous system. Our data also provide important insight into the
      molecular events underlying leptin's control of hepatic autonomic nerve activity
      by implicating PI3K and AMPK pathways. 

PMID- 25589744
TI  - fMRI and EEG predictors of dynamic decision parameters during human reinforcement
      learning.
AB  - What are the neural dynamics of choice processes during reinforcement learning?
      Two largely separate literatures have examined dynamics of reinforcement learning
      (RL) as a function of experience but assuming a static choice process, or
      conversely, the dynamics of choice processes in decision making but based on
      static decision values. Here we show that human choice processes during RL are
      well described by a drift diffusion model (DDM) of decision making in which the
      learned trial-by-trial reward values are sequentially sampled, with a choice made
      when the value signal crosses a decision threshold. Moreover, simultaneous fMRI
      and EEG recordings revealed that this decision threshold is not fixed across
      trials but varies as a function of activity in the subthalamic nucleus (STN) and
      is further modulated by trial-by-trial measures of decision conflict and activity
      in the dorsomedial frontal cortex (pre-SMA BOLD and mediofrontal theta in EEG).
      These findings provide converging multimodal evidence for a model in which
      decision threshold in reward-based tasks is adjusted as a function of
      communication from pre-SMA to STN when choices differ subtly in reward values,
      allowing more time to choose the statistically more rewarding option. 

PMID- 25589745
TI  - Accounting for the delay in the transition from acute to chronic pain: axonal and
      nuclear mechanisms.
AB  - Acute insults produce hyperalgesic priming, a neuroplastic change in nociceptors
      that markedly prolongs inflammatory mediator-induced hyperalgesia. After an acute
      initiating insult, there is a 72 h delay to the onset of priming, for which the
      underlying mechanism is unknown. We hypothesized that the delay is due to the
      time required for a signal to travel from the peripheral terminal to the cell
      body followed by a return signal to the peripheral terminal. We report that when
      an inducer of hyperalgesic priming (monocyte chemotactic protein 1) is
      administered at the spinal cord of Sprague Dawley rats, priming is detected at
      the peripheral terminal with a delay significantly shorter than when applied
      peripherally. Spinally induced priming is detected not only when prostaglandin E2
      (PGE2) is presented to the peripheral nociceptor terminals, but also when it is
      presented intrathecally to the central terminals in the spinal cord. Furthermore,
      when an inducer of priming is administered in the paw, priming can be detected in
      spinal cord (as prolonged hyperalgesia induced by intrathecal PGE2), but only
      when the mechanical stimulus is presented to the paw on the side where the
      priming inducer was administered. Both spinally and peripherally induced priming
      is prevented by intrathecal oligodeoxynucleotide antisense to the nuclear
      transcription factor CREB mRNA. Finally, the inhibitor of protein translation
      reversed hyperalgesic priming only when injected at the site where PGE2 was
      administered, suggesting that the signal transmitted from the cell body to the
      peripheral terminal is not a newly translated protein, but possibly a newly
      expressed mRNA. 

PMID- 25589746
TI  - Hemisphere-dependent attentional modulation of human parietal visual field
      representations.
AB  - Posterior parietal cortex contains several areas defined by topographically
      organized maps of the contralateral visual field. However, recent studies suggest
      that ipsilateral stimuli can elicit larger responses in the right than left
      hemisphere within these areas, depending on task demands. Here we determined the
      effects of spatial attention on the set of visual field locations (the population
      receptive field [pRF]) that evoked a response for each voxel in human topographic
      parietal cortex. A two-dimensional Gaussian was used to model the pRF in each
      voxel, and we measured the effects of attention on not only the center (preferred
      visual field location) but also the size (visual field extent) of the pRF. In
      both hemispheres, larger pRFs were associated with attending to the mapping
      stimulus compared with attending to a central fixation point. In the left
      hemisphere, attending to the stimulus also resulted in more peripheral preferred
      locations of contralateral representations, compared with attending fixation.
      These effects of attention on both pRF size and preferred location preserved
      contralateral representations in the left hemisphere. In contrast, attentional
      modulation of pRF size but not preferred location significantly increased
      representation of the ipsilateral (right) visual hemifield in right parietal
      cortex. Thus, attention effects in topographic parietal cortex exhibit
      hemispheric asymmetries similar to those seen in hemispatial neglect. Our
      findings suggest potential mechanisms underlying the behavioral deficits
      associated with this disorder. 

PMID- 25589747
TI  - Biomarkers of traumatic injury are transported from brain to blood via the
      glymphatic system.
AB  - The nonspecific and variable presentation of traumatic brain injury (TBI) has
      motivated an intense search for blood-based biomarkers that can objectively
      predict the severity of injury. However, it is not known how cytosolic proteins
      released from traumatized brain tissue reach the peripheral blood. Here we show
      in a murine TBI model that CSF movement through the recently characterized
      glymphatic pathway transports biomarkers to blood via the cervical lymphatics.
      Clinically relevant manipulation of glymphatic activity, including sleep
      deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in
      serum S100beta, GFAP, and neuron specific enolase. We conclude that routine TBI
      patient management may limit the clinical utility of blood-based biomarkers
      because their brain-to-blood transport depends on glymphatic activity. 

PMID- 25589749
TI  - Integration of Purkinje cell inhibition by cerebellar nucleo-olivary neurons.
AB  - Neurons in the cerebellar cortex, cerebellar nuclei, and inferior olive (IO) form
      a trisynaptic loop critical for motor learning. IO neurons excite Purkinje cells
      via climbing fibers and depress their parallel fiber inputs. Purkinje cells
      inhibit diverse cells in the cerebellar nuclei, including small GABAergic nucleo
      olivary neurons that project to the IO. To investigate how these neurons
      integrate synaptic signals from Purkinje cells, we retrogradely labeled nucleo
      olivary cells in the contralateral interpositus and lateral nuclei with cholera
      toxin subunit B-Alexa Fluor 488 and recorded their electrophysiological
      properties in cerebellar slices from weanling mice. Nucleo-olivary cells fired
      action potentials over a relatively narrow dynamic range (maximal rate, ~ 70
      spikes/s), unlike large cells that project to premotor areas (maximal rate, ~ 400
      spikes/s). GABA(A) receptor-mediated IPSCs evoked by electrical or optogenetic
      stimulation of Purkinje cells were more than 10-fold slower in nucleo-olivary
      cells (decay time, ~ 25 ms) than in large cells (~ 2 ms), and repetitive
      stimulation at 20-150 Hz evoked greatly summating IPSCs. Nucleo-olivary firing
      rates varied inversely with IPSP frequency, and the timing of Purkinje IPSPs and
      nucleo-olivary spikes was uncorrelated. These attributes contrast with large
      cells, whose brief IPSCs and rapid firing rates can permit well timed
      postinhibitory spiking. Thus, the intrinsic and synaptic properties of these two
      projection neurons from the cerebellar nuclei tailor them for differential
      integration and transmission of their Purkinje cell input.

PMID- 25589750
TI  - Appraisal of brain connectivity in radiologically isolated syndrome by modeling
      imaging measures.
AB  - We hypothesized that appraisal of brain connectivity may shed light on the
      substrate of the radiologically isolated syndrome (RIS), a term applied to
      asymptomatic subjects with brain MRI abnormalities highly suggestive of multiple
      sclerosis. We thus used a multimodal MRI approach on the human brain by modeling
      measures of microstructural integrity of white matter (WM) tracts with those of
      functional connectivity (FC) at the level of resting state networks in RIS
      subjects, demographically matched normal controls (NC), and relapsing-remitting
      (RR) MS patients, also matched with RIS for brain macrostructural damage (i.e.,
      lesions and atrophy). Compared with NC, in both RIS subjects and MS patients
      altered integrity of WM tracts was present. However, RIS subjects showed, at a
      less conservative threshold, lower diffusivities than RRMS patients in distinct
      cerebral associative, commissural, projection, and cerebellar WM tracts,
      suggesting a relatively better anatomical connectivity. FC was similar in NC and
      RIS subjects, even in the presence of important risk factors for MS (spinal cord
      lesions, oligoclonal bands, and dissemination in time on MRI) and increased in
      RRMS patients in two clinically relevant networks subserving "processing"
      (sensorimotor) and "control" (working memory) functions. In RIS, the lack of
      functional reorganization in key brain networks may represent a model of
      "functional reserve," which may become upregulated, with an adaptive or
      maladaptive role, only at a later stage in case of occurrence of clinical
      deficit. 

PMID- 25589748
TI  - Hypoxia silences retrotrapezoid nucleus respiratory chemoreceptors via alkalosis.
AB  - In conscious mammals, hypoxia or hypercapnia stimulates breathing while
      theoretically exerting opposite effects on central respiratory chemoreceptors
      (CRCs). We tested this theory by examining how hypoxia and hypercapnia change the
      activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex
      integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly
      silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby
      C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory
      consequences of Arch activation (10 s) in conscious rats during normoxia,
      hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non
      REM sleep and quiet wake. Compared with normoxia, the breathing frequency
      reduction (Deltaf(R)) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2,
      and absent in 12% FiO2. Tidal volume changes (DeltaV(T)) followed the same trend.
      The effect of hypoxia on Deltaf(R) was not arousal-dependent but was reversed by
      reacidifying the blood (acetazolamide; 3% FiCO2). Deltaf(R) was highly correlated
      with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition
      occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1
      neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic
      breathing about equally during both sleep and wake. RTN neurons are the first
      putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals.
      RTN neurons are silent above pHa 7.5 and increasingly active below this value.
      During hyperoxia, RTN activation maintains breathing despite the inactivity of
      the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation
      increases breathing frequency via pathways that bypass RTN.

PMID- 25589752
TI  - Agonist-dependent modulation of cell surface expression of the cold receptor
      TRPM8.
AB  - The spatial and temporal distribution of receptors constitutes an important
      mechanism for controlling the magnitude of cellular responses. Several members of
      the transient receptor potential (TRP) ion channel family can regulate their
      function by modulating their expression at the plasma membrane (PM) through rapid
      vesicular translocation and fusion. The mechanisms underlying this regulation are
      not completely understood, and the contribution of vesicular trafficking to
      physiological function is unknown. TRPM8 receptors are expressed in mammalian
      peripheral sensory neurons and are essential for the detection of cold
      temperatures. Previously, we showed that TRPM8-containing vesicles are segregated
      into three main pools, immobile at the PM, simple diffusive and corralled
      hopping. Here, we show that channel expression at the PM is modulated by TRPM8
      agonists in F11 and HEK293T cells. Our results support a model in which the
      activation of TRPM8 channels, located at the PM, induces a short-lived
      recruitment of a TRPM8-containing vesicular pool to the cell surface causing a
      transitory increase in the number of functional channels, affecting intrinsic
      properties of cold receptor responses. We further demonstrate the requirement of
      intact vesicular trafficking to support sustained cold responses in the skin of
      mice. 

PMID- 25589751
TI  - Vertebrate epidermal cells are broad-specificity phagocytes that clear sensory
      axon debris.
AB  - Cellular debris created by developmental processes or injury must be cleared by
      phagocytic cells to maintain and repair tissues. Cutaneous injuries damage not
      only epidermal cells but also the axonal endings of somatosensory (touch-sensing)
      neurons, which must be repaired to restore the sensory function of the skin.
      Phagocytosis of neuronal debris is usually performed by macrophages or other
      blood-derived professional phagocytes, but we have found that epidermal cells
      phagocytose somatosensory axon debris in zebrafish. Live imaging revealed that
      epidermal cells rapidly internalize debris into dynamic phosphatidylinositol 3
      monophosphate-positive phagosomes that mature into phagolysosomes using a pathway
      similar to that of professional phagocytes. Epidermal cells phagocytosed not only
      somatosensory axon debris but also debris created by injury to other peripheral
      axons that were mislocalized to the skin, neighboring skin cells, and
      macrophages. Together, these results identify vertebrate epidermal cells as broad
      specificity phagocytes that likely contribute to neural repair and wound healing.

PMID- 25589755
TI  - Rcan1 deficiency impairs neuronal migration and causes periventricular
      heterotopia.
AB  - Periventricular heterotopia (PH) is a cortical malformation characterized by
      aggregation of neurons lining the lateral ventricles due to abnormal neuronal
      migration. The molecular mechanism underlying the pathogenesis of PH is unclear.
      Here we show that Regulators of calcineurin 1 (Rcan1), a Down syndrome-related
      gene, plays an important role in radial migration of rat cortical neurons.
      Downregulation of Rcan1 by expressing shRNA impaired neural progenitor
      proliferation and led to defects in radial migration and PH. Two isoforms of
      Rcan1 (Rcan1-1 and Rcan1-4) are expressed in the rat brain. Migration defects due
      to downregulation of Rcan1 could be prevented by shRNA-resistant expression of
      Rcan1-1 but not Rcan1-4. Furthermore, we found that Rcan1 knockdown significantly
      decreased the expression level of Flna, an F-actin cross-linking protein
      essential for cytoskeleton rearrangement and cell migration, mutation of which
      causes the most common form of bilateral PH in humans. Finally, overexpression of
      FLNA in Rcan1 knockdown neurons prevented migration abnormalities. Together,
      these findings demonstrate that Rcan1 acts upstream from Flna in regulating
      radial migration and suggest that impairment of Rcan1-Flna pathway may underlie
      PH pathogenesis. 

PMID- 25589753
TI  - DAMP signaling is a key pathway inducing immune modulation after brain injury.
AB  - Acute brain lesions induce profound alterations of the peripheral immune response
      comprising the opposing phenomena of early immune activation and subsequent
      immunosuppression. The mechanisms underlying this brain-immune signaling are
      largely unknown. We used animal models for experimental brain ischemia as a
      paradigm of acute brain lesions and additionally investigated a large cohort of
      stroke patients. We analyzed release of HMGB1 isoforms by mass spectrometry and
      investigated its inflammatory potency and signaling pathways by immunological in
      vivo and in vitro techniques. Features of the complex behavioral sickness
      behavior syndrome were characterized by homecage behavior analysis. HMGB1
      downstream signaling, particularly with RAGE, was studied in various transgenic
      animal models and by pharmacological blockade. Our results indicate that the
      cytokine-inducing, fully reduced isoform of HMGB1 was released from the ischemic
      brain in the hyperacute phase of stroke in mice and patients. Cytokines secreted
      in the periphery in response to brain injury induced sickness behavior, which
      could be abrogated by inhibition of the HMGB1-RAGE pathway or direct cytokine
      neutralization. Subsequently, HMGB1-release induced bone marrow egress and
      splenic proliferation of bone marrow-derived suppressor cells, inhibiting the
      adaptive immune responses in vivo and vitro. Furthermore, HMGB1-RAGE signaling
      resulted in functional exhaustion of mature monocytes and lymphopenia, the
      hallmarks of immune suppression after extensive ischemia. This study introduces
      the HMGB1-RAGE-mediated pathway as a key mechanism explaining the complex
      postischemic brain-immune interactions. 

PMID- 25589754
TI  - Topologically dissociable patterns of development of the human cerebral cortex.
AB  - Over 90 years ago, anatomists noted the cortex is thinner in sulci than gyri,
      suggesting that development may occur on a fine scale driven by local topology.
      However, studies of brain development in youth have focused on describing how
      cortical thickness varies over large-scale functional and anatomic regions. How
      the relationship between thickness and local sulcal topology arises in
      development is still not well understood. Here, we investigated the spatial
      relationships between cortical thickness, folding, and underlying white matter
      organization to elucidate the influence of local topology on human brain
      development. Our approach included using both T1-weighted imaging and diffusion
      tensor imaging (DTI) in a cross-sectional sample of 932 youths ages 8-21 studied
      as part of the Philadelphia Neurodevelopmental Cohort. Principal components
      analysis revealed separable development-related processes of regionally specific
      nonlinear cortical thickening (from ages 8-14) and widespread linear cortical
      thinning that have dissociable relationships with cortical topology. Whereas
      cortical thinning was most prominent in the depths of the sulci, early cortical
      thickening was present on the gyri. Furthermore, decline in mean diffusivity
      calculated from DTI in underlying white matter was correlated with cortical
      thinning, suggesting that cortical thinning is spatially associated with white
      matter development. Spatial permutation tests were used to assess the
      significance of these relationships. Together, these data demonstrate that
      cortical remodeling during youth occurs on a local topological scale and is
      associated with changes in white matter beneath the cortical surface. 

PMID- 25589757
TI  - Distributed neural representations of phonological features during speech
      perception.
AB  - A fundamental goal of the human auditory system is to map complex acoustic
      signals onto stable internal representations of the basic sound patterns of
      speech. Phonemes and the distinctive features that they comprise constitute the
      basic building blocks from which higher-level linguistic representations, such as
      words and sentences, are formed. Although the neural structures underlying
      phonemic representations have been well studied, there is considerable debate
      regarding frontal-motor cortical contributions to speech as well as the extent of
      lateralization of phonological representations within auditory cortex. Here we
      used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis
      to investigate the distributed patterns of activation that are associated with
      the categorical and perceptual similarity structure of 16 consonant exemplars in
      the English language used in Miller and Nicely's (1955) classic study of acoustic
      confusability. Participants performed an incidental task while listening to
      phonemes in the MRI scanner. Neural activity in bilateral anterior superior
      temporal gyrus and supratemporal plane was correlated with the first two
      components derived from a multidimensional scaling analysis of a behaviorally
      derived confusability matrix. We further showed that neural representations
      corresponding to the categorical features of voicing, manner of articulation, and
      place of articulation were widely distributed throughout bilateral primary,
      secondary, and association areas of the superior temporal cortex, but not motor
      cortex. Although classification of phonological features was generally bilateral,
      we found that multivariate pattern information was moderately stronger in the
      left compared with the right hemisphere for place but not for voicing or manner
      of articulation. 

PMID- 25589758
TI  - Motor cortex layer V pyramidal neurons exhibit dendritic regression, spine loss,
      and increased synaptic excitation in the presymptomatic hSOD1(G93A) mouse model
      of amyotrophic lateral sclerosis.
AB  - Motor cortex layer V pyramidal neurons (LVPNs) regulate voluntary control of
      motor output and selectively degenerate (along with lower motor neurons) in
      amyotrophic lateral sclerosis. Using dye-filling and whole-cell patch clamping in
      brain slices, together with high-resolution spinning disk confocal z-stack
      mosaics, we characterized the earliest presymptomatic cortical LVPN morphologic
      and electrophysiological perturbations in hSOD1(G93A) (SOD1) mice to date. Apical
      dendritic regression occurred from postnatal day (P) 28, dendritic spine loss
      from P21, and increased EPSC frequency from P21 in SOD1 LVPNs. These findings
      demonstrate extensive early changes in motor cortex of the SOD1 mouse model,
      which thus recapitulates clinically relevant cortical pathophysiology more
      faithfully than previously thought.

PMID- 25589756
TI  - Different patterns of electrical activity lead to long-term potentiation by
      activating different intracellular pathways.
AB  - Deciphering and storing information coded in different firing patterns are
      important properties of neuronal networks, as they allow organisms to respond and
      adapt to external and internal events. Here we report that hippocampal CA1
      pyramidal neurons respond to brief bursts of high-frequency stimulation (HFS) and
      theta burst stimulation (TBS) with long-lasting enhanced responses (long-term
      potentiation [LTP]), albeit by engaging different signaling pathways. TBS induces
      LTP through calpain-1-mediated suprachiasmatic nucleus circadian oscillatory
      protein degradation, ERK activation, and actin polymerization, whereas HFS
      requires adenosine A2 receptors, PKA, and actin polymerization. TBS- but not HFS
      induced LTP is impaired in calpain-1 knock-out mice. However, TBS-induced LTP and
      learning impairment in knock-out mice are restored by activating the HFS pathway.
      Thus, different patterns of rhythmic activities trigger potentiation by
      activating different pathways, and cross talks between these can be used to
      restore LTP and learning when elements of the pathways are impaired. 

PMID- 25589760
TI  - Task-induced modulation of intrinsic functional connectivity networks in the
      behaving rat.
AB  - While resting-state functional magnetic resonance imaging can probe intrinsic
      network connectivity in both human and rodent brain, behavioral modulation of
      these connectivity patterns has not yet been demonstrated in the rodent due to
      the requirements of immobilization or anesthesia for MRI scanning. To enable the
      effects of behavioral tasks on functional connectivity to be measured in freely
      moving, awake rats, implanted carbon paste electrodes (CPEs) were used to monitor
      low-frequency fluctuations of tissue oxygenation. Rats were implanted with CPEs
      in two nodes of the default mode network (DMN) and two nodes in a lateral
      cortical network, revealing amperometric oxygen correlation patterns consistent
      with imaging studies. Using a block design study where rats alternated between
      sustained periods of instrumental response and unscheduled spontaneous behavior,
      task-induced decreases in functional connectivity were observed between the DMN
      node pair, but not in the distinct lateral cortical network, demonstrating
      network-specific modulation of functional connectivity. 

PMID- 25589759
TI  - Primary afferent and spinal cord expression of gastrin-releasing peptide:
      message, protein, and antibody concerns.
AB  - There is continuing controversy relating to the primary afferent neurotransmitter
      that conveys itch signals to the spinal cord. Here, we investigated the DRG and
      spinal cord expression of the putative primary afferent-derived "itch"
      neurotransmitter, gastrin-releasing peptide (GRP). Using ISH, qPCR, and
      immunohistochemistry, we conclude that GRP is expressed abundantly in spinal
      cord, but not in DRG neurons. Titration of the most commonly used GRP antiserum
      in tissues from wild-type and GRP mutant mice indicates that the antiserum is
      only selective for GRP at high dilutions. Paralleling these observations, we
      found that a GRPeGFP transgenic reporter mouse has abundant expression in
      superficial dorsal horn neurons, but not in the DRG. In contrast to previous
      studies, neither dorsal rhizotomy nor an intrathecal injection of capsaicin,
      which completely eliminated spinal cord TRPV1-immunoreactive terminals, altered
      dorsal horn GRP immunoreactivity. Unexpectedly, however, peripheral nerve injury
      induced significant GRP expression in a heterogeneous population of DRG neurons.
      Finally, dual labeling and retrograde tracing studies showed that GRP-expressing
      neurons of the superficial dorsal horn are predominantly interneurons, that a
      small number coexpress protein kinase C gamma (PKCgamma), but that none coexpress
      the GRP receptor (GRPR). Our studies support the view that pruritogens engage
      spinal cord "itch" circuits via excitatory superficial dorsal horn interneurons
      that express GRP and that likely target GRPR-expressing interneurons. The fact
      that peripheral nerve injury induced de novo GRP expression in DRG neurons points
      to a novel contribution of this peptide to pruritoceptive processing in
      neuropathic itch conditions. 

PMID- 25589762
TI  - Inflammasome-induced IL-1beta secretion in microglia is characterized by delayed
      kinetics and is only partially dependent on inflammatory caspases.
AB  - Inflammasomes are multiprotein complexes that link pathogen recognition and
      cellular stress to the processing of the proinflammatory cytokine interleukin
      1beta (IL-1beta). Whereas inflammasome-mediated activation is heavily studied in
      hematopoietic macrophages and dendritic cells, much less is known about
      microglia, resident tissue macrophages of the brain that originate from a
      distinct progenitor. To directly compare inflammasome-mediated activation in
      different types of macrophages, we isolated primary microglia and hematopoietic
      macrophages from adult, healthy rhesus macaques. We analyzed the expression
      profile of NOD (nucleotide-binding oligomerization domain)-like receptors,
      adaptor proteins, and caspases and characterized inflammasome activation and
      regulation in detail. We here demonstrate that primary microglia can respond to
      the same innate stimuli as hematopoietic macrophages. However, microglial
      responses are more persistent due to lack of negative regulation on pro-IL-1beta
      expression. In addition, we show that while caspase 1, 4, and 5 activation is
      pivotal for inflammasome-induced IL-1beta secretion by hematopoietic macrophages,
      microglial secretion of IL-1beta is only partially dependent on these
      inflammatory caspases. These results identify key cell type-specific differences
      that may aid the development of strategies to modulate innate immune responses in
      the brain. 

PMID- 25589763
TI  - Early and persistent abnormal decoding by glial cells at the neuromuscular
      junction in an ALS model.
AB  - Amyotrophic lateral sclerosis (ALS) is a late-onset neuromuscular disease
      characterized by progressive loss of motor neurons (MNs) preceded by
      neuromuscular junction (NMJ) denervation. Despite the importance of NMJ
      denervation in ALS, the mechanisms involved remain unexplored and ill defined.
      The contribution of glial cells in the disease has been highlighted, including
      axonal Schwann cell activation that precedes the decline of motor function and
      the onset of hindlimb paralysis. Because NMJ denervation occurs early in the
      process and that perisynaptic Schwann cells (PSCs), glial cells at the NMJ,
      regulate morphological stability, integrity, and repair of the NMJ, one could
      predict that PSC functions would be altered even before denervation, contributing
      to NMJ malfunctions. We tested this possibility using a slowly progressive model
      of ALS (SOD1(G37R) mice). We observed a normal NMJ organization at a
      presymptomatic stage of ALS (120 d), but PSC detection of endogenous synaptic
      activity revealed by intracellular Ca(2+) changes was enhanced compared with
      their wild-type littermates. This inappropriate PSC decoding ability was
      associated with an increased level of neurotransmitter release and dependent on
      intrinsic glial properties related to enhanced muscarinic receptor activation.
      The alteration of PSC muscarinic receptor functions also persists during the
      preonset stage of the disease and became dependent on MN vulnerability with age.
      Together, these results suggest that PSC properties are altered in the disease
      process in a manner that would be detrimental for NMJ repair. The impairments of
      PSC functions may contribute to NMJ dysfunction and ALS pathogenesis. 

PMID- 25589761
TI  - 5alpha-Reduced neurosteroids sex-dependently reverse central prenatal programming
      of neuroendocrine stress responses in rats.
AB  - Maternal social stress during late pregnancy programs hypothalamo-pituitary
      adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally
      stressed (PNS) offspring display exaggerated HPA axis responses to a physical
      stressor (systemic interleukin-1beta; IL-1beta) in adulthood, compared with
      controls. IL-1beta acts via a noradrenergic relay from the nucleus tractus
      solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular
      nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone
      and 3beta-androstanediol (3beta-diol; 5alpha-reduced metabolites of progesterone
      and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to
      seek reversal of the "programmed" hyper-responsive HPA phenotype.
      Allopregnanolone attenuated ACTH responses to IL-1beta (500 ng/kg, i.v.) in PNS
      females, but not in PNS males. However, 3beta-diol normalized HPA axis responses
      to IL-1beta in PNS males. Impaired testosterone and progesterone metabolism or
      increased secretion in PNS rats was indicated by greater plasma testosterone and
      progesterone concentrations in male and female PNS rats, respectively. Deficits
      in central neurosteroid production were indicated by reduced 5alpha-reductase
      mRNA levels in both male and female PNS offspring in the NTS, and in the PVN in
      males. In PNS females, adenovirus-mediated gene transfer was used to upregulate
      expression of 5alpha-reductase and 3alpha-hydroxysteroid dehydrogenase mRNAs in
      the NTS, and this normalized hyperactive HPA axis responses to IL-1beta. Thus,
      downregulation of neurosteroid production in the brain may underlie HPA axis
      hyper-responsiveness in prenatally programmed offspring, and administration of
      5alpha-reduced steroids acutely to PNS rats overrides programming of hyperactive
      HPA axis responses to immune challenge in a sex-dependent manner. 

PMID- 25589766
TI  - The causal role of the occipital face area (OFA) and lateral occipital (LO)
      cortex in symmetry perception.
AB  - Symmetry is an important cue in face and object perception. Here we used fMRI
      guided transcranial magnetic stimulation (TMS) to shed light on the role of the
      occipital face area (OFA), a key region in face processing, and the lateral
      occipital (LO) cortex, a key area in object processing, in symmetry detection. In
      the first experiment, we applied TMS over the rightOFA, its left homolog
      (leftOFA), rightLO, and vertex (baseline) while participants were discriminating
      between symmetric and asymmetric dot patterns. Stimulation of rightOFA and
      rightLO impaired performance, causally implicating these two regions in detection
      of symmetry in low-level dot configurations. TMS over rightLO but not rightOFA
      also significantly impaired detection of nonsymmetric shapes defined by collinear
      Gabor patches, demonstrating that rightOFA responds to symmetry but not to all
      cues mediating figure-ground segregation. The second experiment showed a causal
      role for rightOFA but not rightLO in facial symmetry detection. Overall, our
      results demonstrate that both the rightOFA and rightLO are sensitive to symmetry
      in dot patterns, whereas only rightOFA is causally involved in facial symmetry
      detection. 

PMID- 25589764
TI  - Homeostatic dysregulation in membrane properties of masticatory motoneurons
      compared with oculomotor neurons in a mouse model for amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motoneuron
      disease with presently no cure. Motoneuron (MN) hyperexcitability is commonly
      observed in ALS and is suggested to be a precursor for excitotoxic cell death.
      However, it is unknown whether hyperexcitability also occurs in MNs that are
      resistant to degeneration. Second, it is unclear whether all the MNs within
      homogeneous motor pools would present similar susceptibility to excitability
      changes since high-threshold MNs innervating fast fatigable muscle fibers
      selectively degenerate compared with low-threshold MNs innervating fatigue
      resistant slow muscle fibers. Therefore, we concurrently examined the
      excitability of ALS-vulnerable trigeminal motoneurons (TMNs) controlling jaw
      musculature and ALS-resistant oculomotor neurons (OMNs) controlling eye
      musculature in a well studied SOD1(G93A) ALS mouse model using in vitro patch
      clamp electrophysiology at presymptomatic ages P8-P12. Our results show that
      hyperexcitability is not a global change among all the MNs, although mutant SOD1
      is ubiquitously expressed. Instead, complex changes occur in ALS-vulnerable TMNs
      based on motor unit type and discharge characteristics. Firing threshold
      decreases among high-threshold TMNs and increases in a subpopulation of low
      threshold TMNs. The latter group was identified based on their linear frequency
      current responses to triangular ramp current injections. Such complex changes in
      MN recruitment were absent in ALS-resistant OMNs. We simulated the observed
      complex changes in TMN excitability using a computer-based jaw closer motor pool
      model. Model results suggest that hypoexcitability may indeed represent emerging
      disease symptomology that causes resistance in muscle force initiation.
      Identifying the cellular and molecular properties of these hypoexcitable cells
      may guide effective therapeutic strategies in ALS.

PMID- 25589765
TI  - Dynamics of EEG rhythms support distinct visual selection mechanisms in parietal
      cortex: a simultaneous transcranial magnetic stimulation and EEG study.
AB  - Using repetitive transcranial magnetic stimulation (rTMS), we have recently shown
      a functional anatomical distinction in human parietal cortex between regions
      involved in maintaining attention to a location [ventral intraparietal sulcus
      (vIPS)] and a region involved in shifting attention between locations [medial
      superior parietal lobule (mSPL)]. In particular, while rTMS interference over
      vIPS impaired target discrimination at contralateral attended locations,
      interference over mSPL affected performance following shifts of attention
      regardless of the visual field (Capotosto et al., 2013). Here, using rTMS
      interference in conjunction with EEG recordings of brain rhythms during the
      presentation of cues that indicate to either shift or maintain spatial attention,
      we tested whether this functional anatomical segregation involves different
      mechanisms of rhythm synchronization. The transient inactivation of vIPS reduced
      the amplitude of the expected parieto-occipital low-alpha (8-10 Hz)
      desynchronization contralateral to the cued location. Conversely, the transient
      inactivation of mSPL, compared with vIPS, reduced the high-alpha (10-12 Hz)
      desynchronization induced by shifting attention into both visual fields.
      Furthermore, rTMS induced a frequency-specific delay of task-related modulation
      of brain rhythms. Specifically, rTMS over vIPS or mSPL during maintenance (stay
      cues) or shifting (shift cues) of spatial attention, respectively, caused a delay
      of alpha parieto-occipital desynchronization. Moreover, rTMS over vIPS during
      stay cues caused a delay of delta (2-4 Hz) frontocentral synchronization. These
      findings further support the anatomo-functional subdivision of the dorsal
      attention network in subsystems devoted to shifting or maintaining covert
      visuospatial attention and indicate that these mechanisms operate in different
      frequency channels linking frontal to parieto-occipital visual regions. 

PMID- 25589767
TI  - Cholinergic basal forebrain structure influences the reconfiguration of white
      matter connections to support residual memory in mild cognitive impairment.
AB  - The fornix and hippocampus are critical to recollection in the healthy human
      brain. Fornix degeneration is a feature of aging and Alzheimer's disease. In the
      presence of fornix damage in mild cognitive impairment (MCI), a recognized
      prodrome of Alzheimer's disease, recall shows greater dependence on other tracts,
      notably the parahippocampal cingulum (PHC). The current aims were to determine
      whether this shift is adaptive and to probe its relationship to cholinergic
      signaling, which is also compromised in Alzheimer's disease. Twenty-five human
      participants with MCI and 20 matched healthy volunteers underwent diffusion MRI,
      behavioral assessment, and volumetric measurement of the basal forebrain. In a
      regression model for recall, there was a significant group * fornix interaction,
      indicating that the association between recall and fornix structure was weaker in
      patients. The opposite trend was present for the left PHC. To further investigate
      this pattern, two regression models were generated to account for recall
      performance: one based on fornix microstructure and the other on both fornix and
      left PHC. The realignment to PHC was positively correlated with free recall but
      not non-memory measures, implying a reconfiguration that is beneficial to
      residual memory. There was a positive relationship between realignment to PHC and
      basal forebrain gray matter volume despite this region demonstrating atrophy at a
      group level, i.e., the cognitive realignment to left PHC was most apparent when
      cholinergic areas were relatively spared. Therefore, cholinergic systems appear
      to enable adaptation to injury even as they degenerate, which has implications
      for functional restoration. 

PMID- 25589768
TI  - CCR2 antagonism alters brain macrophage polarization and ameliorates cognitive
      dysfunction induced by traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a major risk factor for the development of
      multiple neurodegenerative diseases. With respect to the increasing prevalence of
      TBI, new therapeutic strategies are urgently needed that will prevent secondary
      damage to primarily unaffected tissue. Consistently, neuroinflammation has been
      implicated as a key mediator of secondary damage following the initial mechanical
      insult. Following injury, there is uncertainty regarding the role that
      accumulating CCR2(+) macrophages play in the injury-induced neuroinflammatory
      sequelae and cognitive dysfunction. Using CX3CR1(GFP/+)CCR2(RFP/+) reporter mice,
      we show that TBI initiated a temporally restricted accumulation of peripherally
      derived CCR2(+) macrophages, which were concentrated in the hippocampal
      formation, a region necessary for learning and memory. Multivariate analysis
      delineated CCR2(+) macrophages' neuroinflammatory response while identifying a
      novel therapeutic treatment window. As a proof of concept, targeting CCR2(+)
      macrophages with CCX872, a novel Phase I CCR2 selective antagonist, significantly
      reduced TBI-induced inflammatory macrophage accumulation. Concomitantly, there
      was a significant reduction in multiple proinflammatory and neurotoxic mediators
      with this treatment paradigm. Importantly, CCR2 antagonism resulted in a sparing
      of TBI-induced hippocampal-dependent cognitive dysfunction and reduced
      proinflammatory activation profile 1 month after injury. Thus, therapeutically
      targeting the CCR2(+) subset of monocytes/macrophages may provide a new avenue of
      clinical intervention following TBI. 

PMID- 25589769
TI  - Cholinergic control of gamma power in the midbrain spatial attention network.
AB  - The modulation of gamma power (25-90 Hz) is associated with attention and has
      been observed across species and brain areas. However, mechanisms that control
      these modulations are poorly understood. The midbrain spatial attention network
      in birds generates high-amplitude gamma oscillations in the local field potential
      that are thought to represent the highest priority location for attention. Here
      we explore, in midbrain slices from chickens, mechanisms that regulate the power
      of these oscillations, using high-resolution techniques including intracellular
      recordings from neurons targeted by calcium imaging. The results identify a
      specific subtype of neuron, expressing non-alpha7 nicotinic acetylcholine
      receptors, that directly drives inhibition in the gamma-generating circuit and
      switches the network into a primed state capable of producing high-amplitude
      oscillations. The special properties of this mechanism enable rapid, persistent
      changes in gamma power. The brain may employ this mechanism wherever rapid
      modulations of gamma power are critical to information processing. 

PMID- 25589771
TI  - The prefrontal cortex achieves inhibitory control by facilitating subcortical
      motor pathway connectivity.
AB  - Communication between the prefrontal cortex and subcortical nuclei underpins the
      control and inhibition of behavior. However, the interactions in such pathways
      remain controversial. Using a stop-signal response inhibition task and functional
      imaging with analysis of effective connectivity, we show that the lateral
      prefrontal cortex influences the strength of communication between regions in the
      frontostriatal motor system. We compared 20 generative models that represented
      alternative interactions between the inferior frontal gyrus, presupplementary
      motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during
      response inhibition. Bayesian model selection revealed that during successful
      response inhibition, the inferior frontal gyrus modulates an excitatory influence
      of the preSMA on the STN, thereby amplifying the downstream polysynaptic
      inhibition from the STN to the motor cortex. Critically, the strength of the
      interaction between preSMA and STN, and the degree of modulation by the inferior
      frontal gyrus, predicted individual differences in participants' stopping
      performance (stop-signal reaction time). We then used diffusion-weighted imaging
      with tractography to assess white matter structure in the pathways connecting
      these three regions. The mean diffusivity in tracts between preSMA and the STN,
      and between the inferior frontal gyrus and STN, also predicted individual
      differences in stopping efficiency. Finally, we found that white matter structure
      in the tract between preSMA and STN correlated with effective connectivity of the
      same pathway, providing important cross-modal validation of the effective
      connectivity measures. Together, the results demonstrate the network dynamics and
      modulatory role of the prefrontal cortex that underpin individual differences in
      inhibitory control. 

PMID- 25589770
TI  - PAR1-activated astrocytes in the nucleus of the solitary tract stimulate adjacent
      neurons via NMDA receptors.
AB  - Severe autonomic dysfunction, including the loss of control of the
      cardiovascular, respiratory, and gastrointestinal systems, is a common
      comorbidity of stroke and other bleeding head injuries. Previous studies suggest
      that this collapse of autonomic control may be caused by thrombin acting on
      astrocytic protease-activated receptors (PAR1) in the hindbrain. Using calcium
      imaging and electrophysiological techniques, we evaluated the mechanisms by which
      astrocytic PAR1s modulate the activity of presynaptic vagal afferent terminals
      and postsynaptic neurons in the rat nucleus of the solitary tract (NST). Our
      calcium-imaging data show that astrocytic and neuronal calcium levels increase
      after brain slices are treated with the PAR1 agonist SFLLRN-NH2. This increase in
      activity is blocked by pretreating the slices with the glial metabolic blocker
      fluorocitrate. In addition, PAR1-activated astrocytes communicate directly with
      NST neurons by releasing glutamate. Calcium responses to SFLLRN-NH2 in the
      astrocytes and neurons significantly increase after bath application of the
      excitatory amino acid transporter blocker DL-threo-beta-benzyloxyaspartic acid
      (TBOA) and significantly decrease after bath application of the NMDA receptor
      antagonist DL-2-amino-5-phosphonopentanoic acid (DL-AP5). Furthermore, astrocytic
      glutamate activates neuronal GluN2B-containing NMDA receptors. Voltage-clamp
      recordings of miniature EPSCs (mEPSCs) from NST neurons show that astrocytes
      control presynaptic vagal afferent excitability directly under resting and
      activated conditions. Fluorocitrate significantly decreases mEPSC frequency and
      SFLLRN-NH2 significantly increases mEPSC frequency. These data show that
      astrocytes act within a tripartite synapse in the NST, controlling the
      excitability of both postsynaptic NST neurons and presynaptic vagal afferent
      terminals.

PMID- 25589772
TI  - Distinguishing the central drive to tremor in Parkinson's disease and essential
      tremor.
AB  - Parkinson's disease (PD) and essential tremor (ET) are the two most common
      movement disorders. Both have been associated with similar patterns of network
      activation leading to the suggestion that they may result from similar network
      dysfunction, specifically involving the cerebellum. Here, we demonstrate that
      parkinsonian tremors and ETs result from distinct patterns of interactions
      between neural oscillators. These patterns are reflected in the tremors' derived
      frequency tolerance, a novel measure readily attainable from bedside
      accelerometry. Frequency tolerance characterizes the temporal evolution of tremor
      by quantifying the range of frequencies over which the tremor may be considered
      stable. We found that patients with PD (N = 24) and ET (N = 21) were separable
      based on their frequency tolerance, with PD associated with a broad range of
      stable frequencies whereas ET displayed characteristics consistent with a more
      finely tuned oscillatory drive. Furthermore, tremor was selectively entrained by
      transcranial alternating current stimulation applied over cerebellum. Narrow
      frequency tolerances predicted stronger entrainment of tremor by stimulation,
      providing good evidence that the cerebellum plays an important role in pacing
      those tremors. The different patterns of frequency tolerance could be captured
      with a simple model based on a broadly coupled set of neural oscillators for PD,
      but a more finely tuned set of oscillators in ET. Together, these results reveal
      a potential organizational principle of the human motor system, whose disruption
      in PD and ET dictates how patients respond to empirical, and potentially
      therapeutic, interventions that interact with their underlying pathophysiology. 

PMID- 25589774
TI  - Long-delayed expression of the immediate early gene Arc/Arg3.1 refines neuronal
      circuits to perpetuate fear memory.
AB  - Fear memories typically persist for long time periods, and persistent fear
      memories contribute to post-traumatic stress disorder. However, little is known
      about the cellular and synaptic mechanisms that perpetuate long-term memories.
      Here, we find that mouse hippocampal CA1 neurons exhibit biphasic Arc (also known
      as Arg3.1) elevations after fear experience and that the late Arc expression
      regulates the perpetuation of fear memoires. An early Arc increase returned to
      the baseline after 6 h, followed by a second Arc increase after 12 h in the same
      neuronal subpopulation; these elevations occurred via distinct mechanisms.
      Antisense-induced blockade of late Arc expression disrupted memory persistence
      but not formation. Moreover, prolonged fear memories were associated with the
      delayed, specific elimination of dendritic spines and the reactivation of
      neuronal ensembles formed during fear experience, both of which required late Arc
      expression. We propose that late Arc expression refines functional circuits in a
      delayed fashion to prolong fear memory. 

PMID- 25589773
TI  - SIRT1 deficiency in microglia contributes to cognitive decline in aging and
      neurodegeneration via epigenetic regulation of IL-1beta.
AB  - Aging is the predominant risk factor for neurodegenerative diseases. One key
      phenotype as the brain ages is an aberrant innate immune response characterized
      by proinflammation. However, the molecular mechanisms underlying aging-associated
      proinflammation are poorly defined. Whether chronic inflammation plays a causal
      role in cognitive decline in aging and neurodegeneration has not been
      established. Here we report a mechanistic link between chronic inflammation and
      aging microglia and a causal role of aging microglia in neurodegenerative
      cognitive deficits. We showed that SIRT1 is reduced with the aging of microglia
      and that microglial SIRT1 deficiency has a causative role in aging- or tau
      mediated memory deficits via IL-1beta upregulation in mice. Interestingly, the
      selective activation of IL-1beta transcription by SIRT1 deficiency is likely
      mediated through hypomethylating the specific CpG sites on IL-1beta proximal
      promoter. In humans, hypomethylation of IL-1beta is strongly associated with
      chronological age and with elevated IL-1beta transcription. Our findings reveal a
      novel epigenetic mechanism in aging microglia that contributes to cognitive
      deficits in aging and neurodegenerative diseases. 

PMID- 25589776
TI  - Structure-function relationships between aldolase C/zebrin II expression and
      complex spike synchrony in the cerebellum.
AB  - Simple and regular anatomical structure is a hallmark of the cerebellar cortex.
      Parasagittally arrayed alternate expression of aldolase C/zebrin II in Purkinje
      cells (PCs) has been extensively studied, but surprisingly little is known about
      its functional significance. Here we found a precise structure-function
      relationship between aldolase C expression and synchrony of PC complex spike
      activities that reflect climbing fiber inputs to PCs. We performed two-photon
      calcium imaging in transgenic mice in which aldolase C compartments can be
      visualized in vivo, and identified highly synchronous complex spike activities
      among aldolase C-positive or aldolase C-negative PCs, but not across these
      populations. The boundary of aldolase C compartments corresponded to that of
      complex spike synchrony at single-cell resolution. Sensory stimulation evoked
      aldolase C compartment-specific complex spike responses and synchrony. This
      result further revealed the structure-function segregation. In awake animals,
      complex spike synchrony both within and between PC populations across the
      aldolase C boundary were enhanced in response to sensory stimuli, in a way that
      two functionally distinct PC ensembles are coactivated. These results suggest
      that PC populations characterized by aldolase C expression precisely represent
      distinct functional units of the cerebellar cortex, and these functional units
      can cooperate to process sensory information in awake animals. 

PMID- 25589775
TI  - Actions of bupivacaine, a widely used local anesthetic, on NMDA receptor
      responses.
AB  - NMDA receptors mediate excitatory neurotransmission in brain and spinal cord and
      play a pivotal role in the neurological disease state of chronic pain, which is
      caused by central sensitization. Bupivacaine is the indicated local anesthetic in
      caudal, epidural, and spinal anesthesia and is widely used clinically to manage
      acute and chronic pain. In addition to blocking Na(+) channels, bupivacaine
      affects the activity of many other channels, including NMDA receptors.
      Importantly, bupivacaine inhibits NMDA receptor-mediated synaptic transmission in
      the dorsal horn of the spinal cord, an area critically involved in central
      sensitization. We used recombinant NMDA receptors expressed in HEK293 cells and
      found that increasing concentrations of bupivacaine decreased channel open
      probability in GluN2 subunit- and pH-independent manner by increasing the mean
      duration of closures and decreasing the mean duration of openings. Using kinetic
      modeling of one-channel currents, we attributed the observed current decrease to
      two main mechanisms: a voltage-dependent "foot-in-the-door" pore block and an
      allosteric gating effect. Further, the inhibition was state-independent because
      it occurred to the same degree whether the drug was applied before or after
      glutamate stimulation and was mediated by extracellular and intracellular
      inhibitory sites, via hydrophilic and hydrophobic pathways. These results predict
      that clinical doses of bupivacaine would decrease the peak and accelerate the
      decay of synaptic NMDA receptor currents during normal synaptic transmission.
      These quantitative predictions inform possible applications of bupivacaine as
      preventative and therapeutic approaches in chronic pain. 

PMID- 25589778
TI  - Prescription opioids. III. Disposition of oxycodone in oral fluid and blood
      following controlled single-dose administration.
AB  - Oxycodone (OC) is recommended to be included as an analyte tested in the proposed
      Substance Abuse and Mental Health Services Administration (SAMHSA's) Mandatory
      Guidelines for Federal Workplace Drug Testing Programs using Oral Fluid (OF)
      Specimens. This study demonstrates the time course of OC and metabolites,
      noroxycodone (NOC), oxymorphone (OM) and noroxymorphone (NOM), in near
      simultaneous paired OF and whole blood (BL) specimens by liquid chromatography
      tandem mass spectrometry (LC-MS-MS) (limit of detection = 1 ng/mL OF, 5 ng/mL
      BL). A single dose of OC 20 mg controlled-release was administered to 12 healthy
      subjects followed by specimen collections for 52 h. Analyte prevalence was as
      follows: OF, OC > NOC > OM; and BL, OC > NOC > NOM. OC and NOC were frequently
      detected within 15-30 min in OF and 30 min to 2 h in BL. NOM and OM appeared
      between 1.5-5 h post-dose. The mean OF-to-BL (OF:BL) ratios and correlations were
      5.4 for OC (r = 0.719) and 1.0 for NOC (r = 0.651). The period of detection for
      OF exceeded BL by ~2-fold at similar cutoff concentrations. At a 1 ng/mL cutoff
      for OF, the mean detection time was 34 h for OC and NOC. These data provide new
      information that should facilitate interpretation of OC test results. 

PMID- 25589777
TI  - Impact of basal forebrain cholinergic inputs on basolateral amygdala neurons.
AB  - In addition to innervating the cerebral cortex, basal forebrain cholinergic (BFc)
      neurons send a dense projection to the basolateral nucleus of the amygdala (BLA).
      In this study, we investigated the effect of near physiological acetylcholine
      release on BLA neurons using optogenetic tools and in vitro patch-clamp
      recordings. Adult transgenic mice expressing cre-recombinase under the choline
      acetyltransferase promoter were used to selectively transduce BFc neurons with
      channelrhodopsin-2 and a reporter through the injection of an adeno-associated
      virus. Light-induced stimulation of BFc axons produced different effects
      depending on the BLA cell type. In late-firing interneurons, BFc inputs elicited
      fast nicotinic EPSPs. In contrast, no response could be detected in fast-spiking
      interneurons. In principal BLA neurons, two different effects were elicited
      depending on their activity level. When principal BLA neurons were quiescent or
      made to fire at low rates by depolarizing current injection, light-induced
      activation of BFc axons elicited muscarinic IPSPs. In contrast, with stronger
      depolarizing currents, eliciting firing above ~ 6-8 Hz, these muscarinic IPSPs
      lost their efficacy because stimulation of BFc inputs prolonged current-evoked
      afterdepolarizations. All the effects observed in principal neurons were
      dependent on muscarinic receptors type 1, engaging different intracellular
      mechanisms in a state-dependent manner. Overall, our results suggest that
      acetylcholine enhances the signal-to-noise ratio in principal BLA neurons.
      Moreover, the cholinergic engagement of afterdepolarizations may contribute to
      the formation of stimulus associations during fear-conditioning tasks where the
      timing of conditioned and unconditioned stimuli is not optimal for the induction
      of synaptic plasticity.

PMID- 25589780
TI  - Wernicke-Korsakoff syndrome not related to alcohol use: a systematic review.
AB  - OBJECTIVE: Although Wernicke-Korsakoff syndrome (WKS) is a common condition,
      diagnosis remains difficult. WKS not associated with alcohol is rare and thought
      to present differently to alcohol-related WKS. We conducted a systematic review
      of WKS not related to alcohol to enhance understanding of WKS not related to
      alcohol and WKS in general. METHODS: A systematic review was conducted of case
      reports, published in English, of Wernicke's encephalopathy and WKS in patients
      without a history of alcohol-use disorder. Main data sources: MEDLINE, Index
      Medicus. Eligible cases totaled 623. Publication dates ranged from 1867 to 2014.
      Comparisons of clinical presentation were made with published data on samples
      comprising, almost exclusively, alcohol-related WKS. RESULTS: A wide array of
      illnesses precipitated WKS. When diagnosis of WKS was performed postmortem, non
      alcohol-related cases presented a similar number of signs of the classic triad as
      alcohol-related cases (p=0.662, Cohen's w=0.12) but more signs when diagnosed
      antemortem (p<0.001, Cohen's w=0.46). The most common sign was altered mental
      state. Korsakoff syndrome or ongoing memory impairment was reported in 25% of non
      alcohol-related WKS, although cognitive status was not explicitly reported in
      many cases. When duration of memory impairment was reported, 56% had clinically
      obvious memory impairment lasting beyond the period of acute presentation. Non
      alcohol-related WKS was more often associated with female gender, younger age,
      shorter duration of precipitating illness and better survival rate compared to
      alcohol-related WKS. CONCLUSIONS: Thiamine deficiency in the absence of an
      alcohol-use disorder can cause the full clinical spectrum of WKS, including
      chronic cognitive impairment and Korsakoff syndrome.

PMID- 25589779
TI  - A panel of nine cerebrospinal fluid biomarkers may identify patients with
      atypical parkinsonian syndromes.
AB  - BACKGROUND: Patients presenting with parkinsonian syndromes share many clinical
      features, which can make diagnosis difficult. This is important as atypical
      parkinsonian syndromes (APSs) such as progressive supranuclear palsy (PSP),
      multiple system atrophy (MSA) and corticobasal syndrome (CBS) carry a poor
      prognosis, compared with patients with Parkinson's disease (PD). In addition,
      there is overlap between APS and dementia diseases, such as Alzheimer's disease
      (AD) and frontotemporal dementia (FTD). OBJECTIVE: To use a panel of
      cerebrospinal fluid (CSF) biomarkers to differentiate patients with APS from PD
      and dementia. METHODS: A prospective cohort of 160 patients and 30 control
      participants were recruited from a single specialist centre. Patients were
      clinically diagnosed according to current consensus criteria. CSF samples were
      obtained from patients with clinical diagnoses of PD (n=31), PSP (n=33), CBS
      (n=14), MSA (n=31), AD (n=26) and FTD (n=16). Healthy, elderly participants
      (n=30) were included as controls. Total tau (t-tau), phosphorylated tau (p-tau),
      beta-amyloid 1-42 (Abeta42), neurofilament light chain (NFL), alpha-synuclein
      (alpha-syn), amyloid precursor protein soluble metabolites alpha and beta
      (soluble amyloid precursor protein (sAPP)alpha, sAPPbeta) and two
      neuroinflammatory markers (monocyte chemoattractant protein-1 and YKL-40) were
      measured in CSF. A reverse stepwise regression analysis and the false discovery
      rate procedure were used. RESULTS: CSF NFL (p<0.001), sAPPalpha (p<0.001) and a
      syn (p=0.003) independently predicted diagnosis of PD versus APS. Together, these
      nine biomarkers could differentiate patients with PD from APS with an area under
      the curve of 0.95 and subtypes of APS from one another. There was good
      discriminatory power between parkinsonian groups, dementia disorders and healthy
      controls. CONCLUSIONS: A panel of nine CSF biomarkers was able to differentiate
      APS from patients with PD and dementia. This may have important clinical utility
      in improving diagnostic accuracy, allowing better prognostication and earlier
      access to potential disease-modifying therapies.

PMID- 25589781
TI  - Intracranial venous collaterals in cerebral venous thrombosis: clinical and
      imaging impact.
AB  - BACKGROUND AND PURPOSE: Few studies have examined collateral formation in
      patients with cerebral venous thrombosis (CVT). The aim of this study was to
      analyse the impact of baseline intracranial venous collaterals on the clinical
      outcome and imaging features of patients with acute CVT. MATERIAL AND METHODS:
      MRIs from consecutive patients with acute CVT were retrospectively analysed. The
      category system described by Qureshi was used to assess the pattern of venous
      collaterals. Clinical and imaging features and outcomes were analysed using
      bivariate and multivariate models to assess the association of collateral
      patterns with the type of parenchymal lesions and clinical outcome (modified
      Rankin Scale) at 30 and 90 days. RESULTS: One hundred patients were included (77
      women; median age 32 years; and median of 18 months of follow-up). Venous
      collaterals were present in 88% of the patients; type I collaterals in 3
      patients, type II collaterals in 27 patients, and type III collaterals in 58
      patients. Twelve patients did not exhibit any collaterals. Cohen's kappa
      coefficient between evaluators was 0.86. In the bivariate analysis, type III
      collaterals were associated with isolated intracranial hypertension and complete
      recovery, whereas type I collaterals were associated with encephalopathy.
      However, in the multivariate regression analysis, the collateral pattern was not
      associated with clinical presentation, type of brain lesion or outcome.
      CONCLUSIONS: Intracranial venous collaterals are frequently found in patients
      with CVT during the acute phase. However, they do not have an independent effect
      on the type of brain damage, clinical manifestations or prognosis.

PMID- 25589783
TI  - The oncogenic microRNA-21 inhibits the tumor suppressive activity of FBXO11 to
      promote tumorigenesis.
AB  - The microRNA miR-21 is overexpressed in most human cancers and accumulating
      evidence indicates that it functions as an oncogene. Since miRNAs suppress the
      expression of their target genes, we hypothesized that some miR-21 targets may
      act as tumor suppressors, and thus their expression would be anticipated to be
      reduced by the high miR-21 levels observed in various human cancers. By
      microarray analysis and quantitative PCR we identified and validated FBXO11 (a
      member of the F-box subfamily lacking a distinct unifying domain) as a miR-21
      target gene. FBXO11 is a component of the SKP1-CUL1-F-box ubiquitin ligase
      complex that targets proteins for ubiquitination and proteosomal degradation. By
      loss of function and gain of function studies, we show that FBXO11 acts as a
      tumor suppressor, promotes apoptosis and mediates the degradation of the
      oncogenic protein BCL6. The critical role that FBXO11 plays in miR-21-mediated
      tumorigenesis was demonstrated by a rescue experiment, in which silencing FBXO11
      in miR-21KD cancer cells restored their high tumorigenicity. Expression of miR-21
      and FBXO11 are inversely correlated in tumor tissue, and their expression
      correlates with patient survival and tumor grade. High FBXO11 expression
      correlates with better patient survival and lower tumor grade consistent with its
      tumor suppressor activity. In contrast high miR-21 expression, which correlates
      with poor patient survival and higher tumor grade, is consistent with its
      oncogenic activity. Our results identify FBXO11 as a novel miR-21 target gene,
      and demonstrate that the oncogenic miRNA miR-21 decreases the expression of
      FBXO11, which normally acts as a tumor suppressor, and thereby promotes
      tumorigenesis. 

PMID- 25589784
TI  - Anoctamin-6 controls bone mineralization by activating the calcium transporter
      NCX1.
AB  - Anoctamin-6 (Ano6, TMEM16F) belongs to a family of putative Ca(2+)-activated Cl(
      ) channels and operates as membrane phospholipid scramblase. Deletion of Ano6
      leads to reduced skeleton size, skeletal deformities, and mineralization defects
      in mice. However, it remains entirely unclear how a lack of Ano6 leads to a delay
      in bone mineralization by osteoblasts. The Na(+)/Ca(2+) exchanger NCX1 was found
      to interact with Ano6 in a two-hybrid split-ubiquitin screen. Using human
      osteoblasts and osteoblasts from Ano6(-/-) and WT mice, we demonstrate that NCX1
      requires Ano6 to efficiently translocate Ca(2+) out of osteoblasts into the
      calcifying bone matrix. Ca(2+)-activated anion currents are missing in primary
      osteoblasts isolated from Ano6 null mice. Our findings demonstrate the importance
      of NCX1 for bone mineralization and explain why deletion of an ion channel leads
      to the observed mineralization defect: Ano6 Cl(-) currents are probably required
      to operate as a Cl(-) bypass channel, thereby compensating net Na(+) charge
      movement by NCX1. 

PMID- 25589785
TI  - Distinct requirements for HIV-cell fusion and HIV-mediated cell-cell fusion.
AB  - Whether HIV-1 enters cells by fusing with the plasma membrane or with endosomes
      is a subject of active debate. The ability of HIV-1 to mediate fusion between
      adjacent cells, a process referred to as "fusion-from-without" (FFWO), shows that
      this virus can fuse with the plasma membrane. To compare FFWO occurring at the
      cell surface with HIV-cell fusion through a conventional entry route, we designed
      an experimental approach that enabled the measurements of both processes in the
      same sample. The following key differences were observed. First, a very small
      fraction of viruses fusing with target cells participated in FFWO. Second,
      whereas HIV-1 fusion with adherent cells was insensitive to actin inhibitors,
      post-CD4/coreceptor binding steps during FFWO were abrogated. A partial
      dependence of HIV-cell fusion on actin remodeling was observed in CD4(+) T cells,
      but this effect appeared to be due to the actin dependence of virus uptake.
      Third, deletion of the cytoplasmic tail of HIV-1 gp41 dramatically enhanced the
      ability of the virus to promote FFWO, while having a modest effect on virus-cell
      fusion. Distinct efficiencies and actin dependences of FFWO versus HIV-cell
      fusion are consistent with the notion that, except for a minor fraction of
      particles that mediate fusion between the plasma membranes of adjacent cells, HIV
      1 enters through an endocytic pathway. We surmise, however, that cell-cell
      contacts enabling HIV-1 fusion with the plasma membrane could be favored at the
      sites of high density of target cells, such as lymph nodes. 

PMID- 25589786
TI  - A parallel quadruplex DNA is bound tightly but unfolded slowly by pif1 helicase.
AB  - DNA sequences that can form intramolecular quadruplex structures are found in
      promoters of proto-oncogenes. Many of these sequences readily fold into parallel
      quadruplexes. Here we characterize the ability of yeast Pif1 to bind and unfold a
      parallel quadruplex DNA substrate. We found that Pif1 binds more tightly to the
      parallel quadruplex DNA than single-stranded DNA or tailed duplexes. However,
      Pif1 unwinding of duplexes occurs at a much faster rate than unfolding of a
      parallel intramolecular quadruplex. Pif1 readily unfolds a parallel quadruplex
      DNA substrate in a multiturnover reaction and also generates some product under
      single cycle conditions. The rate of ATP hydrolysis by Pif1 is reduced when bound
      to a parallel quadruplex compared with single-stranded DNA. ATP hydrolysis occurs
      at a faster rate than quadruplex unfolding, indicating that some ATP hydrolysis
      events are non-productive during unfolding of intramolecular parallel quadruplex
      DNA. However, product eventually accumulates at a slow rate. 

PMID- 25589787
TI  - beta-Spectrin regulates the hippo signaling pathway and modulates the basal actin
      network.
AB  - Emerging evidence suggests functional regulation of the Hippo pathway by the
      actin cytoskeleton, although the detailed molecular mechanism remains incomplete.
      In a genetic screen, we identified a requirement for beta-Spectrin in the
      posterior follicle cells for the oocyte repolarization process during Drosophila
      mid-oogenesis. beta-spectrin mutations lead to loss of Hippo signaling activity
      in the follicle cells. A similar reduction of Hippo signaling activity was
      observed after beta-Spectrin knockdown in mammalian cells. We further
      demonstrated that beta-spectrin mutations disrupt the basal actin network in
      follicle cells. The abnormal stress fiber-like actin structure on the basal side
      of follicle cells provides a likely link between the beta-spectrin mutations and
      the loss of the Hippo signaling activity phenotype. 

PMID- 25589788
TI  - Heparan sulfate proteoglycans mediate factor XIIa binding to the cell surface.
AB  - Hageman factor (FXIIa) initiates the intrinsic coagulation pathway and triggers
      the kallikrein-kinin and the complement systems. In addition, it functions as a
      growth factor by expressing promitogenic activities toward several cell types.
      FXIIa binds to the cell surface via a number of structurally unrelated surface
      receptors; however, the underlying mechanisms are not yet fully understood. Here,
      we demonstrate that FXIIa utilizes cell membrane-bound glycosaminoglycans to
      interact with the cell surface of human lung fibroblasts (HLF). The combination
      of enzymatic, inhibitory, and overexpression approaches identified a heparan
      sulfate (HS) component of proteoglycans as an important determinant of the FXIIa
      binding capacity of HLF. Moreover, cell-free assays and competition experiments
      revealed preferential binding of FXIIa to HS and heparin over dextran sulfate,
      dermatan sulfate, and chondroitin sulfate A and C. Finally, we demonstrate that
      fibroblasts isolated from the lungs of the patients suffering from idiopathic
      pulmonary fibrosis (IPF) exhibit enhanced FXIIa binding capacity. Increased
      sulfation of HS resulting from elevated HS 6-O-sulfotransferase-1 expression in
      IPF HLF accounted, in part, for this phenomenon. Application of RNA interference
      technology and inhibitors of intracellular sulfation revealed the cooperative
      action of cell surface-associated HS and urokinase-type plasminogen activator
      receptor in the accumulation of FXIIa on the cell surface of IPF HLF. Moreover,
      FXIIa stimulated IPF HLF migration, which was abrogated by pretreatment of cells
      with heparinase I. Collectively, our study uncovers a novel role of HS-type
      glycosaminoglycans in a local accumulation of FXIIa on the cell membrane. The
      enhanced association of FXIIa with IPF HLF suggests its contribution to
      fibrogenesis. 

PMID- 25589790
TI  - Deciphering the combinatorial DNA-binding code of the CCAAT-binding complex and
      the iron-regulatory basic region leucine zipper (bZIP) transcription factor HapX.
AB  - The heterotrimeric CCAAT-binding complex (CBC) is evolutionarily conserved in
      eukaryotic organisms, including fungi, plants, and mammals. The CBC consists of
      three subunits, which are named in the filamentous fungus Aspergillus nidulans
      HapB, HapC, and HapE. HapX, a fourth CBC subunit, was identified exclusively in
      fungi, except for Saccharomyces cerevisiae and the closely related
      Saccharomycotina species. The CBC-HapX complex acts as the master regulator of
      iron homeostasis. HapX belongs to the class of basic region leucine zipper
      transcription factors. We demonstrated that the CBC and HapX bind cooperatively
      to bipartite DNA motifs with a general HapX/CBC/DNA 2:1:1 stoichiometry in a
      class of genes that are repressed by HapX-CBC in A. nidulans during iron
      limitation. This combinatorial binding mode requires protein-protein interaction
      between the N-terminal domain of HapE and the N-terminal CBC binding domain of
      HapX as well as sequence-specific DNA binding of both the CBC and HapX. Initial
      binding of the CBC to CCAAT boxes is mandatory for DNA recognition of HapX. HapX
      specifically targets the minimal motif 5'-GAT-3', which is located at a distance
      of 11-12 bp downstream of the respective CCAAT box. Single nucleotide
      substitutions at the 5'- and 3'-end of the GAT motif as well as different spacing
      between the CBC and HapX DNA-binding sites revealed a remarkable promiscuous DNA
      recognition mode of HapX. This flexible DNA-binding code may have evolved as a
      mechanism for fine-tuning the transcriptional activity of CBC-HapX at distinct
      target promoters. 

PMID- 25589789
TI  - Non-thermal plasma activates human keratinocytes by stimulation of antioxidant
      and phase II pathways.
AB  - Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity
      to control redox-based processes, e.g. wound healing, cancer, and inflammatory
      diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen
      species, it allows stimulation or inhibition of cellular processes in biological
      systems. Our data show that both gene and protein expression is highly affected
      by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase
      II enzyme pathway components were found to act as key controllers orchestrating
      the cellular response in keratinocytes. Additionally, glutathione metabolism,
      which is a marker for NRF2-related signaling events, was affected. Among the most
      robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone
      oxidoreductase 1, and growth factors were found. The roles of NRF2 targets,
      investigated by siRNA silencing, revealed that NRF2 acts as an important switch
      for sensing oxidative stress events. Moreover, the influence of non-thermal
      plasma on the NRF2 pathway prepares cells against exogenic noxae and increases
      their resilience against oxidative species. Via paracrine mechanisms, distant
      cells benefit from cell-cell communication. The finding that non-thermal plasma
      triggers hormesis-like processes in keratinocytes facilitates the understanding
      of plasma-tissue interaction and its clinical application. 

PMID- 25589791
TI  - Traditional serrated adenomas (TSAs) admixed with other serrated (so-called
      precursor) polyps and conventional adenomas: a frequent occurrence.
AB  - BACKGROUND: Traditional serrated adenoma (TSA) is a very characteristic type of
      serrated polyp that has a predilection for the left colon. Recent molecular
      advances have shown two molecular phenotypes of TSA: one associated with BRAF
      mutations and the other with KRAS mutations. The former is associated with
      hyperplastic polyps (HPs) and sessile serrated adenomas (SSAs), while the latter
      is associated with more conventional adenomatous dysplasia. AIMS: The association
      of TSAs with so-called precursor lesions (HPs and SSAs) is not well recognised
      and the purpose of this study was to explore the coexistent presence of HPs, SSAs
      and adenomatous polyps within a large cohort of TSAs. METHODS: In total 149 TSAs
      were examined for the presence of HP, SSA and adenomatous polyps. RESULTS: Seen
      in 83 men and 65 women ranging in age from 32 to 89 years and 127 were left sided
      with 22 in the right colon. Seventy-eight of the 149 TSAs showed evidence of
      another polyp (52.34%): 32 were low-grade tubular/tubulovillous adenomas
      (TAs/TVAs; 41%), 28 were HPs (36%) and 18 were SSAs (23%). Eleven of the 22 right
      sided TSAs were associated with a precursor lesion (1 HP and 7 SSA). In addition,
      five TSAs showed more than one polyp type: TSA with TA/TVA and HP (3); TSA with
      TA/TVA and SSA (2). The TAs/TVAs were adjacent to the TSA but occurred as a
      separate discrete polyp, while HPs and SSAs were intermingled with the TSA and
      present at the base and surface of the lesion. CONCLUSIONS: More than 50% of TSAs
      are associated with a precursor lesion or adjacent TA/TVA. Their recognition is
      important as this may have surveillance and management ramifications.

PMID- 25589792
TI  - Utility of bone marrow examination for workup of fever of unknown origin in
      patients with HIV/AIDS.
AB  - AIMS: The utility of bone marrow aspiration and biopsy (BMAB) as a diagnostic
      tool in patients with HIV/AIDS and fever of unknown origin (FUO) is a subject of
      debate. Because highly active antiretroviral therapy has reduced incidence of
      opportunistic infections, it is important to reassess the efficacy of BMAB for
      this diagnostic purpose. To our knowledge, no such studies have been performed in
      Harris County which has the highest incidence of HIV in the state of Texas.
      METHODS: We reviewed all BMABs from patients with HIV/AIDS and FUO or persistent
      cytopenia(s) from 2007 to 2011. RESULTS: Of 57 evaluable patients, BMAB was
      positive in 24 samples by acid fast bacilli (AFB) or Gomori methenamine silver
      (GMS) stains (17.5%), presence of granuloma and/or lymphohistiocytic aggregates
      (31.6%), culture (21.0%) or a combination. Cultures demonstrated Mycobacterium
      avium/intracellulare (4), M tuberculosis (2), M gordonae (1), Histoplasma
      capsulatum (3) and Cryptococcus neoformans (2). There were three cases in which a
      pathogen was grown in culture but that had a negative of 'direct examination' on
      tissue sections (negative AFB and GMS special stains, no morphological evidence
      of granuloma/lymphohistiocytic infiltrates). CONCLUSIONS: This study supports the
      use of diagnostic BMAB as a rapid decision-making tool in patients with HIV and
      FUO in the proper clinical setting. BMAB demonstrated infection-related evidence
      prior to positive bone marrow culture in 75% of cases. Special stains and blood
      cultures had similar diagnostic yield, but BMAB offers faster results. Thus, this
      procedure assists in clinical decision making and the refinement of treatment in
      a more timely manner.

PMID- 25589793
TI  - A dynamic model of the hypoxia-inducible factor 1a (HIF-1a) network.

PMID- 25589794
TI  - Assessing Trends in Women's Violence via Data Triangulation: Arrests,
      Convictions, Incarcerations, & Victim Reports.
AB  - Constructionist theories suggest the national rise in female violence arrests may
      be policy-generated because arrest statistics are produced by violent behavior
      and changing official responses (e.g., net-widening enforcement policies).
      Normative theories attribute the rise to female behavior changes (e.g., in
      response to increased freedoms or hardships). We examine whether any narrowing of
      the arrest gender gap is borne out across offense types of varying measurement
      reliability, in victimization data, and across two post-arrest criminal justice
      stages. Advanced time-series analyses over 1980-2003 support the constructionist
      position - first, all sources show little or no increase in women's rates for the
      more reliably measured offenses of homicide and robbery, and for rape; second,
      the assault gender gap narrows for arrests, but holds stable in victimization
      data; third, the assault gender gap narrows moderately for convictions, but is
      stable for imprisonment, indicating spill-over effects of more expansive arrest
      policies. Several factors have produced greater female representation in
      "criminal assault" arrests including (i) proactive policing targeting and
      formally responding to minor violence and in private contexts, (ii)
      interventionist developmental epistemologies that blur distinctions among
      violence types and circumstances, (iii) the rise of social movements recognizing
      "hidden" victims, (iv) law and order political messages stressing greater
      accountability, and (v) the somewhat greater decline in male compared to female
      violence in the late 1990s. The problem of women's violence is largely a social
      construction. Rather than women becoming more violent, changes in the management
      of violence increasingly mask differences in the violence levels of women and
      men.

PMID- 25589795
TI  - Residential Segregation in Metropolitan Established Immigrant Gateways and New
      Destinations, 1990-2000.
AB  - In the 1990s, many immigrants bypassed established gateways like Los Angeles, New
      York, Chicago, and Miami to create new immigrant destinations across the U.S. In
      this paper, we examine how segregation and spatial assimilation might differ
      between established gateways and new destinations among the 150 largest
      metropolitan areas. Using data from the 1990 and 2000 censuses, we calculate
      levels of dissimilarity for Hispanics and Asians by nativity for these two
      gateway types. Our findings show that segregation levels are consistently lower
      in new destinations. However, Hispanics in new destinations experienced
      significant increases segregation during the 1990s, suggesting a convergence in
      residential patterns by destination type. Nevertheless, in both destinations the
      native-born are less segregated than the foreign born-consistent with immigrant
      spatial incorporation. Finally, socioeconomic indicators are generally consistent
      with predictions of spatial assimilation.

PMID- 25589796
TI  - Household context, generational status, and English proficiency among the
      children of African immigrants in the US.
AB  - This study examines how household and parental-level determinants affect English
      proficiency among the children of African immigrants in the US. Within immigrant
      families, the study finds that children's level of proficiency has a stronger
      positive association with the proficiency of their mothers than with that of
      their fathers. Children's level of English proficiency significantly increases as
      the number other English-proficient children within their household increases.
      These impacts are stronger on the proficiency levels of first compared to second
      generation children. Levels of proficiency are, however, lowest among children in
      families from Portuguese speaking countries followed by their counterparts in
      families from countries where indigenous languages and Arabic are dominant.
      Although proficiency levels generally improve with increasing generational
      status, these improvements are smallest for children in families from Portuguese
      speaking countries. Except for children in families from English speaking
      countries, the largest improvements to proficiency with increasing generational
      status was observed among children in families from indigenous language
      backgrounds.

PMID- 25589797
TI  - Interaction of Comparative Cancer Risk and Cancer Efficacy Perceptions on Cancer
      Related Information Seeking and Scanning Behaviors.
AB  - This study examined the interaction between perceived cancer risk and self
      efficacy related to cancer screening on cancer-related information seeking and
      scanning behaviors (SSB) among the general population. Individuals completed a
      cross-sectional survey, were classified into 1 of 4 clusters based on their
      relative risk and self-efficacy belief scores (i.e., high relative risk and high
      self-efficacy, high relative risk and low self-efficacy, low relative risk and
      high self-efficacy, and low relative risk and low self-efficacy), and asked about
      their information SSB related to the colonoscopy, prostate-specific antigen test,
      or mammogram. A national probability sample of 2,489 adults aged 40 to 70 took
      part in this study. Individuals who perceived themselves to be at high relative
      risk for cancer and had high self-efficacy beliefs in performing cancer-screening
      behaviors generally reported the highest amounts of SSB for cancer-screening
      information, compared to the others.

PMID- 25589798
TI  - Use of 99m-technetium-glucoheptonate as a tracer for brain tumor imaging: An
      overview of its strengths and pitfalls.
AB  - Brain tumors represent a vexing clinical problem in oncology due to their
      increasing incidence, difficulties in treatment and high rates of recurrence. It
      is especially challenging to evaluate the posttreatment disease status because
      differentiation of recurrence from treatment-induced changes (radiation necrosis)
      is not possible with the use of magnetic resonance imaging, the most commonly
      used imaging method in this setting. Various functional imaging methods,
      including positron emission tomography and single photon emission computed
      tomography (SPECT) have been employed in this context. SPECT with 99m-technetium
      (99mTc)-glucoheptonate (GHA) has shown promising results for differentiation of
      recurrent brain tumor from radiation necrosis. In this review, we have discussed
      in details the basics of 99mTc-GHA SPECT imaging in brain tumor along with the
      available literature in this regard. 

PMID- 25589799
TI  - Validation of virtual spectrometer created in RADlab1.03.
AB  - Spectrometer is used to perform various in vitro tests. The ability to
      successfully perform these tests depends on technologist's skill. Therefore,
      proper training of technologists is mandatory in gamma spectrometry. During the
      training, they need to have sufficient practice to gain sound theoretical and
      practical knowledge. High cost of spectrometer and risk of their damage during
      independent practice may hamper the process of proper training. Hence, there is a
      need of cheaper and more feasible option. Virtual spectrometer created in
      RADlab1.03 can address this issue. The immediate objective of this paper is to
      validate this virtual spectrometer so as to be used as an educational and
      research tool for trainees. Virtual spectrometer was calibrated using Cs-137
      standard source and Cs-137 spectrum was recorded by positioning 28106 Bq Cs-137
      source at 2.35 cm above top surface of the well, 1 cm above from the bottom of
      the well and at the bottom of the well. Ba-133 and Co-60 spectrum were also
      recorded. The experiments were repeated with real spectrometer for exactly the
      same conditions as applied to the virtual spectrometer. The paired t-test was
      applied to find the difference in mean photopeak at 5% level of significance. The
      sample data provided satisfactory evidence that mean photopeak obtained with real
      as well as virtual spectrometer were same at P value of 4.641 * 10(-4),1.57 * 10(
      12),1.40 * 10(-24), 1.26 * 10(-16), and 8.7 * 10(-9) for Cs-137 (photopeak: 664
      keV, Co-60 (photopeak: 1181 keV), Co-60 (photopeak: Co-1348 keV), Ba-133
      (photopeak: 304 keV) and Ba-133 (photopeak: 364 keV) respectively. 

PMID- 25589800
TI  - Does the intensity of diffuse thyroid gland uptake on F-18 fluorodeoxyglucose
      positron emission tomography/computed tomography scan predict the severity of
      hypothyroidism? Correlation between maximal standardized uptake value and serum
      thyroid stimulating hormone levels.
AB  - CONTEXT: F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed
      tomography (PET/CT) scan and hypothyroidism. AIMS: The aim was to determine
      whether the intensity of diffuse thyroid gland uptake on F-18 FDG PET/CT scans
      predicts the severity of hypothyroidism. MATERIALS AND METHODS: A retrospective
      analysis of 3868 patients who underwent F-18 FDG PET/CT scans, between October
      2012 and June 2013 in our institution for various oncological indications was
      done. Out of them, 106 (2.7%) patients (79 females, 27 males) presented with
      bilateral diffuse thyroid gland uptake as an incidental finding. These patients
      were investigated retrospectively and various parameters such as age, sex,
      primary cancer site, maximal standardized uptake value (SUVmax), results of
      thyroid function tests (TFTs) and fine-needle aspiration cytology results were
      noted. The SUVmax values were correlated with serum thyroid stimulating hormone
      (S. TSH) levels using Pearson's correlation analysis. STATISTICAL ANALYSIS USED:
      Pearson's correlation analysis. RESULTS: Clinical information and TFT (serum FT3,
      FT4 and TSH levels) results were available for 31 of the 106 patients (27
      females, 4 males; mean age 51.5 years). Twenty-six out of 31 patients (84%) were
      having abnormal TFTs with abnormal TSH levels in 24/31 patients (mean S. TSH:
      22.35 MUIU/ml, median: 7.37 MUIU/ml, range: 0.074-211 MUIU/ml). Among 7 patients
      with normal TSH levels, 2 patients demonstrated low FT3 and FT4 levels. No
      significant correlation was found between maximum standardized uptake value and
      TSH levels (r = 0.115, P > 0.05). CONCLUSIONS: Incidentally detected diffuse
      thyroid gland uptake on F-18 FDG PET/CT scan was usually associated with
      hypothyroidism probably caused by autoimmune thyroiditis. Patients should be
      investigated promptly irrespective of the intensity of FDG uptake with TFTs to
      initiate replacement therapy and a USG examination to look for any suspicious
      nodules.

PMID- 25589801
TI  - Role of FDG PET/CT in assessing response to targeted therapy in metastatic lung
      cancers: Morphological versus metabolic criteria.
AB  - INTRODUCTION: Targeted therapeutic agents are indicated in metastatic lung
      cancers. These being receptor specific therapies, manifestation of response can
      be best assessed by estimating the metabolic activity of tumor, rather than the
      size. This retrospective analysis studied metabolic and morphological response on
      Positron Emission Tomography (PET) and Computed Tomography (CT), respectively to
      these agents. MATERIALS AND METHODS: Thirty-one patients (23 males, 8 females
      with an age range of 42-77 years) with Epidermal Growth Factor Receptor (EGFR)
      positive metastatic lung cancer on Gefitinib, who underwent PET/CT, at baseline
      and at 4-6 weeks, were assessed by Response Evaluation Criteria In Solid Tumors
      [RECIST] 1.1 and European Organization for Research and Treatment of Cancer
      (EORTC) criteria. RESULTS: Concordance between RECIST 1.1 and EORTC was seen in
      26 (83.7%) patients. Discordance was seen in 5 (16.3%) patients. In patients with
      discordance, the results were confirmed by follow-up imaging. Metabolic EORTC
      criteria changed the disease status from stable disease to partial response (3
      out of 5) and progressive disease (2 out of 5) in these five patients.
      CONCLUSIONS: Metabolic criteria using PET/CT could accurately predict response as
      well as disease progression early in the course of targeted therapy, compared to
      morphologic criteria. In addition, early metabolic response assessment can
      predict refractoriness of therapy.

PMID- 25589802
TI  - Technetium-99m dimercaptosuccinic acid scan in evaluation of renal cortical
      scarring: Is it mandatory to do single photon emission computerized tomography?
AB  - OBJECTIVES: Renal cortical scintigraphy with technetium-99m (Tc-99m)
      dimercaptosuccinic acid (DMSA) is the method of choice to detect acute
      pyelonephritis and cortical scarring. Different acquisition methods have been
      used: Planar parallel-hole or pinhole collimation and single photon emission
      tomography (SPECT). This study compared planar parallel-hole cortical
      scintigraphy and dual-head SPECT for detection of cortical defects. PATIENTS AND
      METHODS: We retrospectively reviewed 190 consecutive patients with 380 kidneys
      and 200 DMSA scans referred to rule out renal cortical scarring. The diagnoses
      were 52 vesicoureteric reflux, 61 recurrent urinary tract infection, 39
      hydronephrosis, 20 renal impairment, and 18 hypertension. All patients were
      imaged 3 h after injection of Tc-99m DMSA with SPECT and planar imaging
      (posterior, anterior, left, and right posterior oblique views). For each patient,
      planar and SPECT images were evaluated at different sittings, in random order.
      Each kidney was divided into three cortical segments (upper, middle and lower)
      and was scored as normal or reduced uptake. The linear correlation coefficient
      for the number of abnormal segments detected between planner and SPECT techniques
      was calculated. RESULTS: From 200 DMSA scans, 100 scans were positive for scar in
      SPECT images, from which only 95 scans were positive for scar in planner imaging.
      Out of the five mismatched scans, three scans were for patients with renal
      impairment and high background activity and two scans were for very small scars.
      No significant difference was seen in the average number of abnormal segments
      detected by planar versus SPECT imaging (P = 0.31). The average correlation
      coefficient between was high (r = 0.91 - 0.92). CONCLUSIONS: Tc-99m DMSA renal
      cortical scanning using SPECT offers no statistically significant diagnostic
      advantage over multiple views planar imaging for detection of cortical defect.

PMID- 25589804
TI  - Primary breast osteosarcoma: A diagnostic challenge.
AB  - Extraskeletal osteosarcomas account for < 1% of the soft tissue sarcomas and are
      known to more often localize in soft tissues of the lower extremities. Primary
      osteosarcomas of the breast are extremely rare. A majority of the reported cases
      were in fact initially erroneously diagnosed and treated as primary breast
      carcinomas. We recently got to treat an interesting case of a primary breast
      osteosarcoma and discuss its evaluation and management with added emphasis on the
      incremental role of technetium 99-methylene diphosphonate (Tc-99m) bone
      scintigraphy in its clinical diagnosis. Tc-99m uptake can occasionally be seen in
      the delayed bone scintigraphy images of extra skeletal malignancies, but the
      uptakes are considered to be typically less intense than the uptakes noted in
      primary skeletal malignancies. Extraskeletal osteosarcomas are however the
      exceptions to this rule, the intense uptake in bone scintigraphy further aided in
      an accurate preoperative diagnosis and management of our patient. 

PMID- 25589803
TI  - Potential role of (18)F-2-fluoro-2-deoxy-glucose positron emission
      tomography/computed tomography imaging in patients presenting with generalized
      lymphadenopathy.
AB  - Generalized lymphadenopathy is a common and often vexing clinical problem caused
      by various inflammatory, infective and malignant diseases. We aimed to review
      briefly and highlight the potential role of (18)F-2-fluoro-2-deoxy-glucose ((18)F
      FDG) positron emission tomography/computed tomography (PET/CT) in such patients.
      (18)F-FDG PET/CT can play an important role in the management of generalized
      lymphadenopathy. It can help in making an etiological diagnosis; can detect
      extranodal sites of involvement and employed for monitoring response to therapy. 

PMID- 25589805
TI  - Solitary hypervascular liver metastasis from neuroendocrine tumor mimicking
      hepatocellular cancer: All that glitters is not gold.
AB  - Neuroendocrine tumor metastases to the liver can mimic primary hepatocellular
      carcinoma (HCC) on imaging, cytology, and core biopsy. We present a case study
      along with the literature review of a patient who presented as a solitary liver
      mass mimicking HCC and subsequently underwent a partial hepatectomy. The
      histopathology and immunohistochemisrty of the resected specimen revealed
      metastatic neuroendocrine carcinoma. Positron emission tomography (PET) scan with
      (68)Ga-DOTA-NaI-octreotide ((68)Ga-DOTANOC) localized the primary tumor in the
      ileum. A curative follow-up surgery for resection of the small bowel containing
      the primary tumor was carried out. This case illustrates the shortcomings of
      routine imaging methods, utility of immunocytochemistry and the importance of
      (68)Ga-DOTANOC PET in determining the metastatic spread as well as the origin of
      neuroendocrine tumors (NETs). This case report attempts to highlight the current
      imaging paradigms and management strategy of midgut and other NET's at the point
      of detection, staging and follow-up. 

PMID- 25589806
TI  - Use of yttrium-90 hydroxyapatite radiosynovectomy as a primary modality of
      treatment in diffuse pigmented villonodular synovitis of the knee joint: A first
      case report.
AB  - Pigmented villonodular synovitis (PVNS) is a rare, relatively benign, intra
      articular lesion characterized by a slowly progressive proliferation of synovial
      tissue. Knee is the most frequently involved joint. Localized and diffuse forms
      of synovial involvement were reported. In extensive diffuse cases, total
      synovectomy is needed, almost impossible to achieve. Hence, other treatment
      modalities such as intra-articular injection of yttrium-90 have been tried and
      shown to be effective in reducing the rate of local recurrence with "acceptable"
      joint damage. Radiosynovectomy is based on the irradiation of the joint synovium
      by the intra-articular administration of various beta-emitting
      radiopharmaceuticals. We describe the first case report of use of yttrium-90
      hydroxyapatite particulates in a 33-year-old male who presented with diffuse PVNS
      of knee joint as a primary modality of treatment. 

PMID- 25589807
TI  - (18)F-fluoro-deoxyglucose positron emission tomography-computed tomography in
      initial assessment and diagnosis of right atrial angiosarcoma with widespread
      visceral metastases: A rare case report and review of the literature.
AB  - Cardiac angiosarcoma is the most common primary cardiac sarcoma in adults.
      Primary cardiac tumors are rare and have nonspecific clinical presentation, thus
      making its diagnosis challenging. Clinically, patients present with advanced
      disease demonstrating metastatic disease at initial presentation itself. It
      commonly metastasizes to lung, liver, brain, and bone; however metastases to
      lymph nodes, adrenal glands, spleen and skin has also been seen. We describe a
      case of right atrial angiosarcoma with extensive visceral metastases involving
      brain, lungs, liver, pancreas, kidney, and lymph nodes, demonstrated on contrast
      enhanced (18)F-fluoro-deoxyglucose positron emission tomography-computed
      tomography (FDG PET-CT). To the best of our knowledge metastases to pancreas and
      kidney have not been reported so far in the literature. With our report, we
      emphasize on the initial use of FDG PET-CT in workup of cardiac angiosarcoma for
      accurate staging and prognostication of this disease. 

PMID- 25589808
TI  - Osteopetrosis: radiological & radionuclide imaging.
AB  - Osteopetrosis is a rare inherited bone disease where bones harden and become
      abnormally dense. While the diagnosis is clinical, it also greatly relies on
      appearance of the skeleton radiographically. X-ray, radionuclide bone
      scintigraphy and magnetic resonance imaging have been reported to identify
      characteristics of osteopetrosis. We present an interesting case of a 59-year-old
      man with a history of bilateral hip fractures. He underwent (99m)Tc-methylene
      diphosphonate whole body scan supplemented with single-photon emission computed
      tomography/computed tomography of spine, which showed increased uptake in the
      humeri, tibiae and femora, which were in keeping with osteopetrosis. 

PMID- 25589809
TI  - Synchronous thoracic and abdominal enteric duplication cysts: Accurate detection
      with (99m)Tc-pertechnetate scintigraphy.
AB  - Enteric duplication cysts (EDCs) are uncommon congenital anomalies, which can
      occur anywhere along the gastrointestinal tract and vary greatly in presentation,
      size, location and symptoms. Ectopic gastric mucosa is reported to be found in 20
      30% of these duplications. (99m)Tc-pertechnetate scintigraphy is a useful
      modality for preoperative localization of the ectopic functioning gastric mucosa
      in the EDCs. We report a case where (99m)Tc-pertechnetate scintigraphy was useful
      in detecting synchronous thoracic and abdominal duplication cysts with
      functioning gastric mucosa thus having an impact on the patient management. 

PMID- 25589810
TI  - Fluoro deoxyglucose positron emission tomography-computerized tomography in
      primary staging and response assessment of a rare case of primary pleural
      synovial sarcoma.
AB  - Primary pleural sarcomas constitute <1% of all primary lung cancers. Synovial
      sarcomas of the pleura are extremely rare. They may be mistaken for malignant
      mesothelioma or other spindle cell tumors, but the confirmation is by histology
      and immunohistochemistry. Synovial sarcomas are aggressive with a high incidence
      of recurrence. In this case report, we present the 18-fluoride-fluoro
      deoxyglucose (FDG) positron emission tomography-computerized tomography (PET-CT)
      findings of patient with primary pleural synovial cell sarcoma. The pretreatment
      and postchemotherapy FDG PET-CT scans are presented. The role of FDG PET-CT in
      initial staging and response assessment in this interesting case of pleural
      synovial sarcoma is presented. 

PMID- 25589811
TI  - Rare solitary focal tuberculous involvement of liver masquerading as hepatic
      metastasis on FDG PET/CT in a case of fibular round cell tumor.
AB  - Finding of focal 18F-fluoro-deoxyglucose (FDG) uptake in liver on FDG positron
      emission tomography/computed tomography (FDG PET/CT) in a known case of
      malignancy is often considered to be metastases. We report a similar finding on
      FDG PET/CT in a case of Ewing's sarcoma of thigh, which turned out to be of
      tuberculous etiology, an unusual cause of false positive FDG uptake in the liver.

PMID- 25589812
TI  - (18)F-fluorodeoxyglucose-positron-emission tomography/computed tomography staging
      of mucinous tubular and spindle cell carcinoma of the kidney.
AB  - Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an
      extremely rare carcinoma of the kidney, which develops by malignant
      differentiation of the collecting ducts or the loop of Henle. The tumor can occur
      at all ages, with 4 times higher prevalence in females than in males. A 62-year
      old female patient presented with an asymptomatic mass lesion in the left kidney.
      The ultrasound revealed a hyperechogenic mass lesion measuring 4 cm in diameter
      and centrally located in the left kidney. Computed tomography (CT) revealed an
      isodense mass lesion measuring 4 cm in diameter and posterolaterally located in
      the left kidney. Magnetic resonance imaging revealed a renal mass of 4 cm in
      diameter with hypervascular contrast uptake. For primary staging, (18)F
      fluorodeoxyglucose-positron-emission tomography ((18)FDG-PET)/CT revealed left
      renal cell carcinoma (RCC) with a maximum standard uptake value of 6.7. The
      patient underwent transperitoneal radical nephrectomy. The immunohistochemical
      examination revealed MTSCC-K. (18)FDG-PET/CT provides 81-89% sensitivity and 83
      100% specificity in primary staging of the renal cancers, in diagnosing
      metastatic RCC, and monitoring the response to therapy. Its use in the staging of
      MTSCC of the kidney has not been previously described in the literature. This
      case highlights the usefulness of (18)FDG-PET/CT in the staging of this rare
      tumor. 

PMID- 25589813
TI  - Contrast-enhanced (18)F-fluorodeoxyglucose positron emission tomography/computed
      tomography in immunoglobulin G4-related retroperitoneal fibrosis.
AB  - Immunoglobulin G4 (IgG4)-related disease encompasses a wide variety of immune
      disorders previously thought be distinct. IgG4-related retroperitoneal fibrosis
      is one such entity. Metabolic imaging with (18)F-fluorodeoxyglucose ((18)F-FDG)
      positron emission tomography/computed tomography (PET/CT) can be useful in the
      management of IgG4-related retroperitoneal fibrosis. We here discuss the case of
      63-year-old male with IgG4-related retroperitoneal fibrosis and the role, (18)F
      FDG PET/CT played in his management. 

PMID- 25589814
TI  - Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography
      in evaluation of residual intramuscular myxoma.
AB  - Intramuscular myxoma (IM) is a rare benign neoplasm. In a patient diagnosed with
      IM of left thigh, we report the utility of a postoperative fluorine-18
      fluorodeoxyglucose positron emission tomography-computed tomography scan in
      assessing the efficacy of surgical excision. 

PMID- 25589782
TI  - Higher mortality in patients with right hemispheric intracerebral haemorrhage:
      INTERACT1 and 2.
AB  - BACKGROUND AND PURPOSE: Controversy exists over the prognostic significance of
      the affected hemisphere in stroke. We aimed to determine the relationship between
      laterality of acute intracerebral haemorrhage (ICH) and poor clinical outcomes.
      METHODS: A subsidiary analysis of the INTERACT Pilot and INTERACT2 studies-
      randomised controlled trials of patients with spontaneous acute ICH with elevated
      systolic blood pressure (BP), randomly assigned to intensive (target systolic BP
      <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Outcomes were the
      combined and separate end points of death and major disability (modified Rankin
      scale (mRS) scores of 3-6, 6 and 3-5, respectively) at 90 days. RESULTS: A total
      of 2708 patients had supratentorial/hemispheric ICH and information on mRS at 90
      days. Patients with right hemispheric ICH (1327, 49%) had a higher risk of death
      at 90 days compared to those with left hemispheric ICH after adjustment for
      potential confounding variables (OR, 1.77 (95% CI 1.33 to 2.37)). There were no
      differences between patients with right and left hemispheric ICH regarding the
      combined end point of death or major disability or major disability in the
      multivariable-adjusted models (1.07 (0.89 to 1.29) and 0.85 (0.72 to 1.01),
      respectively). CONCLUSIONS: Right hemispheric lesion was associated with
      increased risk of death in patients with acute ICH. The laterality of the ICH
      does not appear to affect the level of disability in survivors. TRIAL
      REGISTRATION NUMBER: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00226096 and NCT00716079.

PMID- 25589815
TI  - "Pseudo-thyroid lobe": A diagnostic conundrum caused by ossified anterior
      longitudinal ligament on bone scan.
AB  - Radionuclide bone imaging is one of the most commonly performed nuclear medicine
      procedure around the world and characterized by its high sensitivity and
      relatively low specificity. False positive findings on a bone scan are very
      common; however, dense uptake over unilateral ossified anterior longitudinal
      ligament appearing as single thyroid lobe on a bone scan has not been described
      in the literature. 

PMID- 25589816
TI  - An uncommon case showing three different pathologies on (99m)technetium-methylene
      diphosphonate bone scintigraphy.
AB  - (99m)Technetium-methylene diphosphonate bone scintigraphy (BS) has an important
      role in evaluating skeletal pathology, especially its extent. Incidental extra
      osseous uptake may sometimes be seen in soft-tissue pathologies. We present a 64
      year-old female with skull base osteomyelitis referred for BS which revealed
      involvement of the skull base on the left side, uptake was also noted in
      bilateral lungs secondary to hypercalcemia of renal failure and in the D12-L1
      vertebrae as the patient had a history of Pott's spine. This is perhaps a unique
      case showing three findings each of a different etiology in the same scan. 

PMID- 25589817
TI  - Mesenteric metastases of purely myxoid liposarcoma: An unusual behavior of
      primary tumor depicted on fludeoxyglucose positron emission
      tomography/computerized tomography.
AB  - A 48-year-old male patient with purely myxoid liposarcoma was referred to
      fludeoxyglucose positron emission tomography/computerized tomography (FDG PET/CT)
      for restaging. FDG PET/CT images showed a hypodense well-defined intermuscular
      mass with mild FDG uptake in the right gluteal region. In addition, multiple mild
      hypermetabolic masses that had similar characteristics with the aforementioned
      lesion were also revealed in the mesenteric region of abdomen and pelvis. 

PMID- 25589818
TI  - Gliomatosis cerebri mimicking encephalitis evaluated using fluorine-18
      fluorodeoxyglucose: Positron emission tomography/computed tomography.
AB  - Gliomatosis cerebri (GC) is a rare condition in which an infiltrative glial
      neoplasm spreads through the brain with preservation of the underlying structure.
      F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (FDG
      PET/CT) has an important role in demonstrating the appropriate metabolism and
      differentiating pathologies mimicking GC on CT and magnetic resonance imaging. We
      describe imaging findings of FDG PET/CT in GC in a 9-year-old male child
      mimicking encephalitis. 

PMID- 25589821
TI  - (175)Yb-TTHMP for bone pain palliation.

PMID- 25589820
TI  - (18)F-FDG PET/CT imaging in a seldom case of primary malignant melanoma of
      duodenum.

PMID- 25589822
TI  - Varying Coefficient Models for Sparse Noise-contaminated Longitudinal Data.
AB  - In this paper we propose a varying coefficient model for highly sparse
      longitudinal data that allows for error-prone time-dependent variables and time
      invariant covariates. We develop a new estimation procedure, based on covariance
      representation techniques, that enables effective borrowing of information across
      all subjects in sparse and irregular longitudinal data observed with measurement
      error, a challenge in which there is no adequate solution currently. More
      specifically, sparsity is addressed via a functional analysis approach that
      considers the observed longitudinal data as noise contaminated realizations of a
      random process that produces smooth trajectories. This approach allows for
      estimation based on pooled data, borrowing strength from all subjects, in
      targeting the mean functions and auto- and cross-covariances to overcome sparse
      noisy designs. The resulting estimators are shown to be uniformly consistent.
      Consistent prediction for the response trajectories are also obtained via
      conditional expectation under Gaussian assumptions. Asymptotic distribution of
      the predicted response trajectories are derived, allowing for construction of
      asymptotic pointwise confidence bands. Efficacy of the proposed method is
      investigated in simulation studies and compared to the commonly used local
      polynomial smoothing method. The proposed method is illustrated with a sparse
      longitudinal data set, examining the age-varying relationship between calcium
      absorption and dietary calcium. Prediction of individual calcium absorption
      curves as a function of age are also examined.

PMID- 25589823
TI  - The Educational Attainment Process Among Adolescents with Disabilities And
      Children of Parents with Disabilities.
AB  - This article uses data from the National Longitudinal Survey of Youth 1997
      (NLSY97) to examine the relationship between disability, parental and youth
      university expectations in 1997, and youth high school completion and university
      enrolment by 2003. Results indicate that educational attainment is not equal for
      young adults with and without disabilities in the United States. Parents-but not
      adolescents-are likely to reduce their educational expectations when adolescents
      have a mild or serious disability, net of school performance. These parental-but
      not adolescent-expectations are significantly associated with high school
      completion. Finally, even after controlling for educational expectations and
      school performance, youth with serious disabilities are much less likely to
      graduate from high school than youth without disabilities. Despite the
      considerable strides made in the implementation of the Individuals with
      Disabilities Education Act, students with disabilities are not achieving
      educational parity in graded schooling.

PMID- 25589819
TI  - Forced diuresis (18)F-fluorodeoxyglucose positron emission tomography/contrast
      enhanced in detection of carcinoma of urinary bladder diverticulum.
AB  - Urinary bladder diverticular carcinomas are uncommon with a lesser incidence of
      0.8-10% and its diagnosis still remains a challenge. Cystoscopy is the most
      reliable method, but evaluating diverticulum with narrow orifices is difficult.
      Before the initiation of appropriate treatment, proper detection of bladder
      diverticular carcinoma and its locoregional and distant sites of involvement is
      necessary. Here, we present a case of 48-year-old male with urinary bladder
      diverticular carcinoma detected by forced diuretic (18)F-fluorodeoxyglucose
      positron emission tomography/computerized tomography ((18)F-FDG PET/CT). This
      case also highlights the significance of forced diuretic (18)F-FDG PET/CT in the
      detection, staging, and response evaluation of bladder diverticular carcinoma. 

PMID- 25589824
TI  - Interaction of methotrexate, an anticancer agent, with copper(II) ions:
      coordination pattern, DNA-cleaving properties and cytotoxic studies.
AB  - The acid-base properties and the Cu(II) binding processes of methotrexate (MTX)
      were characterized by selected spectroscopic techniques and potentiometric
      measurements. The pH titration data showed that MTX behaves as a triprotic
      ligand. The deprotonation constants were determined for alpha-COOH and gamma-COOH
      groups and (N1)H+ from the pteridine ring. Taking all the obtained results into
      consideration, a coordination pattern was proposed. The DNA-cleaving activity and
      reactive oxygen species (ROS) generation were investigated for both MTX and the
      Cu(II)-MTX system. The complex displayed a promising nuclease activity toward
      plasmid DNA in the presence of hydrogen peroxide. Interestingly, the induction of
      ROS, such as hydroxyl radicals, superoxide anions or singlet oxygen, was excluded
      and a different mechanism of DNA degradation was proposed. As MTX is now commonly
      used in anticancer therapy i.e. against lung cancer, basic cell-based studies
      were carried out to establish if its Cu(II) complex exhibits higher cytotoxic
      properties than the ligand alone. Activities of both compounds were also tested
      against colon carcinoma. Moreover, the determined values of IC50 were confronted
      with the cytotoxic activity of cisplatin.

PMID- 25589825
TI  - QSPR analysis of some agonists and antagonists of alpha-adrenergic receptors.
AB  - Thirty-three compounds belonging to the sympatholytics and sympathomimetics were
      analyzed during the study. The biological activity data for the parameters of
      binding affinity to the alpha1- and alpha2-adrenergic receptors together with
      parameters of the logarithm of the partition coefficient n-octanol/water (log P)
      were performed using a semi-empirical calculations methods for isolated molecules
      (in vacuo) and for the molecules placed in an aqueous environment. Additionally,
      the chromatographic retention data were used as extra dependent variables of the
      structural parameters for a part of the considered compounds. Finally, all those
      groups of parameters were analyzed using MLR, PCA, and FA methods for the
      classification of studied compounds according to their chemical structures and
      pharmacological activity to the adrenoceptors.

PMID- 25589826
TI  - Changes in Drinking Patterns Across the Transition to College Among First-Year
      College Males.
AB  - Few studies examine changes in drinking behavior during the transition from high
      school to college. Using a sample of 239 first-year males, we hypothesized that
      participants would increase drinking from pre-college to the first month of
      college. Results reveal a general trend toward increased drinking upon entering
      college. Caucasians increased drinking more than non-Caucasians. Social
      expectancies of alcohol moderated increases in drinking behavior. These findings
      indicate that differential changes in drinking behavior occur among incoming
      college males. Interventions with college students need to address both
      preventing heavy consumption and alcohol-related problems in pre-college light
      drinkers and in reducing these behaviors among pre-college heavy drinkers.

PMID- 25589827
TI  - Methods for the morphological and functional evaluation of microvascular damage
      in systemic sclerosis.
AB  - Systemic sclerosis is a connective tissue disease characterized by alterations in
      microvascular structure and function. In these patients, numerous studies have
      demonstrated a relationship between capillary morphology and peripheral blood
      perfusion. Nailfold videocapillaroscopy reveals the peripheral microvascular
      morphology and thus allows classification and scoring of capillary abnormalities
      with respect to different microangiopathy patterns (early, active, and late).
      Laser Doppler flowmetry and laser speckle contrast analysis can be used to
      estimate cutaneous blood flow through microvessels and to assess and quantify
      blood perfusion at peripheral sites. These two methods are also used to identify
      changes in digital blood perfusion after the infusion of vasodilators. 

PMID- 25589829
TI  - Major changes and improvements of dialysis therapy in Korea: review of end-stage
      renal disease registry.
AB  - The Korean Society of Nephrology (KSN) launched a nationwide end-stage renal
      disease (ESRD) patient registry in 1985 called the Insan Prof. Byung-Suk Min
      Memorial ESRD Patient Registry. KSN members voluntarily participate in this
      registry, which has been collecting data through the Internet since 2000. The KSN
      ESRD patient registry data were reviewed to elucidate the major changes and
      improvements in dialysis therapy in Korea. The data review revealed: a rapid
      increase in the number of patients with ESRD; an increase in the number of
      patients with diabetic nephropathy; a decrease in the proportion of patients
      undergoing peritoneal dialysis; an increase in the role of private dialysis
      clinics; an increase in the number of elderly patients undergoing dialysis and
      the number of patients undergoing long-term dialysis; a decrease in mean blood
      pressure and an increase in pulse pressure; improvement in anemia treatment;
      improvement in dialysis adequacy; and improvement in the survival of patients
      undergoing dialysis. In conclusion, improvements have been made in blood pressure
      control, anemia treatment, and dialysis adequacy despite increases in the number
      of elderly patients, diabetic patients, and patients on long-term dialysis during
      the last two decades in Korea. 

PMID- 25589831
TI  - Can improvements in our physiological understanding yield information on the
      utility of endothelial progenitor cell capture stents?

PMID- 25589828
TI  - Avoiding or coping with severe hypoglycemia in patients with type 2 diabetes.
AB  - Hypoglycemia is a major barrier to achieving the glycemic goal in patients with
      type 2 diabetes. In particular, severe hypoglycemia, which is defined as an event
      that requires the assistance of another person to actively administer
      carbohydrates, glucagon, or take other corrective actions, is a serious clinical
      concern in patients with diabetes. If severe hypoglycemia is not managed
      promptly, it can be life threatening. Hypoglycemia-associated autonomic failure
      (HAAF) is the main pathogenic mechanism behind severe hypoglycemia. Defective
      glucose counter-regulation (altered insulin secretion, glucagon secretion, and an
      attenuated increase in epinephrine during hypoglycemia) and a lack of awareness
      regarding hypoglycemia (attenuated sympathoadrenal activity) are common
      components of HAAF in patients with diabetes. There is considerable evidence that
      hypoglycemia is an independent risk factor for cardiovascular disease. In
      addition, hypoglycemia has a significant influence on the quality of life of
      patients with diabetes. To prevent hypoglycemic events, the setting of glycemic
      goals should be individualized, particularly in elderly individuals or patients
      with complicated or advanced type 2 diabetes. Patients at high-risk for the
      future development of severe hypoglycemia should be selected carefully, and
      intensive education with reinforcement should be implemented. 

PMID- 25589830
TI  - Is tenofovir disoproxil fumarate an all-powerful weapon in the treatment of
      chronic hepatitis B?

PMID- 25589832
TI  - Association of metabolic syndrome with coronary artery calcification.

PMID- 25589833
TI  - Long-term efficacy of tenofovir disoproxil fumarate therapy after multiple
      nucleos(t)ide analogue failure in chronic hepatitis B patients.
AB  - BACKGROUND/AIMS: The efficacy of tenofovir disoproxil fumarate (TDF) for the
      treatment of chronic hepatitis B (CHB) patients following prior treatment failure
      with multiple nucleos(t)ide analogues (NAs) is not well defined, especially in
      Asian populations. In this study we investigated the efficacy and safety of TDF
      rescue therapy in CHB patients after multiple NA treatment failure. METHODS: The
      study retrospectively analyzed 52 CHB patients who experienced failure with two
      or more NAs and who were switched to regimens containing TDF. The efficacy and
      safety assessments included hepatitis B virus (HBV) DNA undetectability,
      hepatitis B envelop antigen (HBeAg) seroclearance, alanine transaminase (ALT)
      normalization and changes in serum creatinine and phosphorus levels. RESULTS: The
      mean HBV DNA level at baseline was 5.4 +/- 1.76 log10 IU/mL. At a median duration
      of 34.5 months of TDF treatment, the cumulative probabilities of achieving
      complete virological response (CVR) were 25.0%, 51.8%, 74.2%, and 96.7% at 6, 12,
      24, and 48 months, respectively. HBeAg seroclearance occurred in seven of 48
      patients (14.6%). ALT levels were normalized in 27 of 31 patients (87.1%) with
      elevated ALT at baseline. Lower levels of HBV DNA at baseline were significantly
      associated with increased CVR rates (p < 0.001). However, CVR rates did not
      differ between TDF monotherapy or combination therapy with other NAs, and were
      not affected by mutations associated with resistance to NAs. No significant
      adverse events were observed. CONCLUSIONS: TDF is an efficient and safe rescue
      therapy for CHB patients after treatment failure with multiple NAs.

PMID- 25589834
TI  - Impact of an endothelial progenitor cell capturing stent on coronary
      microvascular function: comparison with drug-eluting stents.
AB  - BACKGROUND/AIMS: Although drug-eluting stents (DESs) effectively reduce
      restenosis following percutaneous coronary intervention (PCI), they also delay re
      endothelialization and impair microvascular function, resulting in adverse
      clinical outcomes. Endothelial progenitor cell (EPC) capturing stents, by
      providing a functional endothelial layer on the stent, have beneficial effects on
      microvascular function. However, data on coronary microvascular function in
      patients with EPC stents versus DESs are lacking. METHODS: Seventy-four patients
      who previously underwent PCI were enrolled in this study. Microvascular function
      was evaluated 6 months after PCI based on the index of microvascular resistance
      (IMR) and the coronary flow reserve (CFR). IMR was calculated as the ratio of the
      mean distal coronary pressure at maximal hyperemia to the inverse of the
      hyperemic mean transit time (hTmn). The CFR was calculated by dividing the hTmn
      by the baseline mean transit time. RESULTS: Twenty-one patients (age, 67.2 +/-
      9.6 years; male:female, 15:6) with an EPC stent and 53 patients (age, 61.5 +/-
      14.7 years; male:female, 40:13) with second-generation DESs were included in the
      study. There were no significant differences in the baseline clinical and
      angiographic characteristics of the two groups. Angiography performed 6 months
      postoperatively did not show significant differences in their CFR values.
      However, patients with the EPC stent had a significantly lower IMR than patients
      with second-generation DESs (median, 25.5 [interquartile range, 12.85 to 28.18]
      vs. 29.0 [interquartile range, 15.42 to 39.23]; p = 0.043). CONCLUSIONS:
      Microvascular dysfunction was significantly improved after 6 months in patients
      with EPC stents compared to those with DESs. The complete re-endothelialization
      achieved with the EPC stent may provide clinical benefits over DESs, especially
      in patients with microvascular dysfunction.

PMID- 25589835
TI  - Clinical impact of routine follow-up coronary angiography after second- or third
      generation drug-eluting stent insertion in clinically stable patients.
AB  - BACKGROUND/AIMS: In the bare-metal stent era, routine follow-up coronary
      angiography (RFU CAG) was used to ensure stent patency. With the advent of drug
      eluting stents (DESs) with better safety and efficacy profiles, RFU CAG has been
      performed less often. There are few data on the clinical impact of RFU CAG after
      second- or third-generation DES implantation in clinically stable patients with
      coronary artery disease; the aim of this study was to examine this issue.
      METHODS: We analyzed clinical outcomes retrospectively of 259 patients who were
      event-free at 12-month after stent implantation and did not undergo RFU CAG
      (clinical follow-up group) and 364 patients who were event-free prior to RFU CAG
      (angiographic follow-up group). Baseline characteristics were compared between
      the groups. RESULTS: The Kaplan-Meier estimated total survival and major adverse
      cardiac event (MACE)-free survival did not differ between the groups (p = 0.100
      and p = 0.461, respectively). The cumulative MACE rate was also not different
      between the groups (hazard ratio, 0.85; 95% confidence interval, 0.35 to 2.02).
      In the angiographic follow-up group, 8.8% revascularization was seen at RFU CAG.
      CONCLUSIONS: RFU CAG did not affect long-term clinical outcome after second- or
      third-generation DES implantation in clinically stable patients.

PMID- 25589836
TI  - Pleural fluid characteristics of pleuropulmonary paragonimiasis masquerading as
      pleural tuberculosis.
AB  - BACKGROUND/AIMS: Pleuropulmonary paragonimiasis produces no specific symptoms or
      radiologic findings, allowing for the possibility of misdiagnosis. We evaluated
      the specific clinical and pleural fluid features of pleuropulmonary
      paragonimiasis masquerading as pleural tuberculosis. METHODS: We retrospectively
      analyzed the clinical and radiologic characteristics of 20 patients diagnosed
      with pleuropulmonary paragonimiasis between 2001 and 2011. RESULTS: In total, 17
      patients presented with respiratory symptoms, including dyspnea (30%), hemoptysis
      (20%), cough (20%), and pleuritic chest pain (15%). Chest radiographs revealed
      intrapulmonary parenchymal lesions, including air-space consolidation (30%),
      nodular opacities (20%), cystic lesions (15%), ground-glass opacities (10%), and
      pneumothorax (5%). A pleural fluid examination revealed eosinophilia, low glucose
      levels, and high lactate dehydrogenase (LDH) levels in 87%, 76%, and 88% of the
      patients, respectively. These traits helped to distinguish pleuropulmonary
      paragonimiasis from other pleural diseases such as parapneumonic effusion,
      malignancy, and pleural tuberculosis. CONCLUSIONS: Pleuropulmonary paragonimiasis
      is often initially misdiagnosed as other pleural diseases. Therefore, it is
      important to establish the correct diagnosis. In patients with unexplained
      pleural effusion living in paragonimiasis-endemic areas, pleural fluid obtained
      by thoracentesis should be examined to distinguish pleuropulmonary
      paragonimiasis. When marked eosinophilia, high LDH levels, and low glucose levels
      are identified in pleural fluid, physicians could consider a diagnosis of
      pleuropulmonary paragonimiasis.

PMID- 25589837
TI  - Proteomic differences with and without ozone-exposure in a smoking-induced
      emphysema lung model.
AB  - BACKGROUND/AIMS: Acute exacerbations in chronic obstructive pulmonary disease may
      be related to air pollution, of which ozone is an important constituent. In this
      study, we investigated the protein profiles associated with ozone-induced
      exacerbations in a smoking-induced emphysema model. METHODS: Mice were divided
      into the following groups: group I, no smoking and no ozone (NS + NO); group II,
      no smoking and ozone (NS + O); group III, smoking and no ozone (S + NO); and
      group IV, smoking and ozone (S + O). Bronchoalveolar lavage, the mean linear
      intercept (MLI) on hematoxylin and eosin staining, nano-liquid chromatography
      tandem mass spectrometry (LC-MS/MS), and Western blotting analyses were
      performed. RESULTS: The MLIs of groups III (S + NO) and IV (S + O) (45 +/- 2 and
      44 +/- 3 um, respectively) were significantly higher than those of groups I (NS +
      NO) and II (NS + O) (26 +/- 2 and 23 +/- 2 um, respectively; p < 0.05). Fourteen
      spots that showed significantly different intensities on image analyses of two
      dimensional (2D) protein electrophoresis in group I (NS + NO) were identified by
      LC-MS/MS. The levels of six proteins were higher in group IV (S + O). The levels
      of vimentin, lactate dehydrogenase A, and triose phosphate isomerase were
      decreased by both smoking and ozone treatment in Western blotting and proteomic
      analyses. In contrast, TBC1 domain family 5 (TBC1D5) and lamin A were increased
      by both smoking and ozone treatment. CONCLUSIONS: TBC1D5 could be a biomarker of
      ozone-induced lung injury in emphysema.

PMID- 25589838
TI  - Metabolic syndrome criteria as predictors of subclinical atherosclerosis based on
      the coronary calcium score.
AB  - BACKGROUND/AIMS: The aim was to determine which of three sets of metabolic
      syndrome (MetS) criteria (International Diabetes Federation [IDF], National
      Cholesterol Education Program Adult Treatment Panel III [ATP III], and European
      Group for the Study of Insulin Resistance [EGIR]) best predicts the coronary
      artery calcification (CAC) score in a cross-sectional study. This has not been
      evaluated in previous studies. METHODS: A total of 24,060 subjects were screened
      for CAC by multi-detector computed tomography. The presence of CAC was defined as
      a CAC score > 0. The odds ratio for the presence of CAC was analyzed for three
      different sets of MetS criteria and according to number of MetS components.
      RESULTS: CAC was observed in 12.6% (3,037) of the subjects. Patients with MetS,
      as defined by the IDF, ATP III, and EGIR criteria, had a CAC rate of 23.0%,
      25.1%, and 29.5%, respectively (p < 0.001). Comparisons of C statistics for
      multivariate regression models revealed no significant difference among the three
      sets of criteria. After adjustment for risk factors, the ATP III criteria
      produced a slightly higher odds ratio for CAC compared with the other criteria,
      but this difference was not significant. The risk factor-adjusted odds ratio for
      the presence of CAC increased from 1 to 1.679 as the number of MetS components
      defined by ATP III increased from 0 to >= 3 (p for trend < 0.001). CONCLUSIONS:
      The presence of MetS was associated with the presence of CAC. There was no
      significant difference among the three sets of MetS criteria in terms of the
      ability to predict CAC. An increase in the number of MetS components was
      associated with an increased odds of CAC.

PMID- 25589839
TI  - The association between an abnormal post-voiding urine volume and a lower
      estimated glomerular filtration rate in patients with type 2 diabetes with no
      voiding symptoms.
AB  - BACKGROUND/AIMS: Diabetic cystopathy is a frequent complication of diabetes
      mellitus. This study assessed the association between the post-voiding residual
      (PVR) urine volume and diabetic nephropathy in type 2 diabetics with no voiding
      symptoms. METHODS: This study investigated 42 patients with type 2 diabetes who
      were followed regularly at our outpatient clinic between July 1, 2008 and June
      30, 2009. No patient had voiding problems or International Prostate Symptom
      Scores (IPSSs) >= 12. An urologist performed the urological evaluations and the
      PVR was measured using a bladder scan. A PVR > 50 mL on two consecutive voids was
      considered abnormal, which was the primary study outcome. RESULTS: The mean
      patient age was 60 +/- 10 years; the IPSS score was 3.7 +/- 3.3; and the diabetes
      duration was 11.9 +/- 7.8 years. Seven of the 42 patients (16.7%) had a PVR > 50
      mL. The presence of overt proteinuria or microalbuminuria was associated with an
      increased risk of a PVR > 50 mL (p < 0.01). Patients with a PVR > 50 mL had a
      significantly lower estimated glomerular filtration rate (eGFR) compared with
      those with a PVR <= 50 mL (59.2 +/- 27.1 mL/min/1.73 m(2) vs. 28.7 +/- 23.3
      mL/min/1.73 m(2); p < 0.001). Multivariate logistic analysis revealed that a
      lower eGFR (odds ratio, 0.94; 95% confidence interval, 0.88 to 0.99; p = 0.04)
      was a significant risk factor for a PVR > 50 mL. CONCLUSIONS: Patients with
      diabetic nephropathy had a significantly higher PVR and a lower eGFR was
      associated with an abnormal PVR.

PMID- 25589840
TI  - The efficacy of low-dose transdermal fentanyl in opioid-naive cancer patients
      with moderate-to-severe pain.
AB  - BACKGROUND/AIMS: Little is known about the efficacy of low-dose transdermal
      fentanyl (TDF) patches in opioid-naive patients with moderate-to-severe cancer
      pain. METHODS: This study had an open-label, prospective design, and was
      conducted between April 2007 and February 2009 in seven tertiary cancer
      hospitals; 98 patients were enrolled. TDF was started using a low-dose
      formulation (12.5 ug/hr), and the dose was adjusted according to the clinical
      situation of individual patients. Pain intensity, the TDF doses used, and adverse
      events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to
      treat and per-protocol principles. RESULTS: Of the 98 patients enrolled, 64 (65%)
      completed the study. The median pain intensity decreased from 6.0 to 3.0 (p <
      0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was
      consistent across groups separated according to gender (p < 0.001), age (p <
      0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain
      intensity (p < 0.001). The decrease in pain intensity was significantly greater
      in the severe group compared with the moderate group (mean +/- SD, 5.10 +/- 2.48
      vs. 2.48 +/- 1.56; p < 0.001). TDF dose (27.8 ug/hr vs. 24.8 ug/hr, p = 0.423)
      and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain
      control were not different between the two pain-intensity groups. Patients had
      AEs of only mild or moderate intensity; among these, nausea (38%) was the most
      common, followed by vomiting (22%) and somnolence (22%). CONCLUSIONS: Low-dose
      TDF was an effective treatment for patients with cancer pain of moderate-to
      severe intensity. Further randomized trials assessing the efficacy of TDF for
      severe pain and/or optimal starting doses are warranted.

PMID- 25589841
TI  - Utilization of the respiratory virus multiplex reverse transcription-polymerase
      chain reaction test for adult patients at a Korean tertiary care center.
AB  - BACKGROUND/AIMS: Respiratory viruses (RVs) are considered to be important
      respiratory pathogens in adult patients, and the multiplex reverse transcription
      polymerase chain reaction (RT-PCR) test is used frequently in adult patients with
      respiratory infections. However, clinical data regarding utilization of the
      multiplex RT-PCR test for RVs are lacking. METHODS: We investigated the
      utilization of the multiplex RT-PCR test for RVs at Chung-Ang University Hospital
      in Seoul, Korea, between January 2012 and April 2013. RESULTS: During the study
      period, the multiplex RT-PCR test was performed for 291 adult patients. The test
      frequency was 4.9% of rapid influenza antigen detection tests and 0.8% of
      respiratory bacterial culture studies. A turnaround time of < 48 hours was
      observed in 25.9% of positive tests. Most of the tests were performed for
      admitted patients (97.9%) with a community-acquired infection (84.2%) during the
      flu season (82.5%). RVs were detected in 81 of 291 cases (27.8%). The RV
      positivity rates for community- and hospital-acquired infections did not differ
      (28.6% vs. 23.9%, p = 0.52). Of 166 patients with pneumonia, 44 (26.5%) had a
      viral infection. Among the patients with RV-associated pneumonia, an RV other
      than influenza was detected in 20 patients (45.4%). CONCLUSIONS: The multiplex RT
      PCR test for RVs was infrequently performed at a tertiary care center, and the
      test results were often reported late. The test was most often performed for
      admitted adult patients with community-acquired infections during the flu season.
      The utilization of multiplex RT-PCR testing for RVs in current clinical practice
      should be improved.

PMID- 25589843
TI  - Cholangiocarcinoma with a paraneoplastic leukemoid reaction mimicking a pyogenic
      liver abscess.

PMID- 25589842
TI  - Mortality in patients with rheumatoid arthritis-associated interstitial lung
      disease treated with an anti-tumor necrosis factor agent.
AB  - BACKGROUND/AIMS: To evaluate the impact on mortality of anti-tumor necrosis
      factor (anti-TNF) treatment of rheumatoid arthritis-associated interstitial lung
      disease (RA-ILD). METHODS: We retrospectively reviewed the medical records of 100
      RA-ILD patients who visited our tertiary care medical center between 2004 and
      2011, identified those treated with an anti-TNF agent, divided patients into non
      survivor and survivor groups and evaluated their clinical characteristics and
      causes of death. RESULTS: A total of 24 RA-ILD patients received anti-TNF
      therapy, of whom six died (25%). Mean age at initiation of anti-TNF therapy was
      significantly higher in the nonsurvivor versus survivor group (76 years [range,
      66 to 85] vs. 64 years [range, 50 to 81], respectively; p = 0.043). The mean
      duration of anti-TNF treatment in the non-survivor group was shorter (7 months
      [range, 2 to 14] vs. 23 months [range, 2 to 58], respectively; p = 0.030). The
      duration of anti-TNF therapy in all nonsurviving patients was < 12 months.
      Pulmonary function test results at ILD diagnosis, and cumulative doses of disease
      modifying drugs and steroids, did not differ between groups. Five of the six
      deaths (83%) were related to lung disease, including two diffuse alveolar
      hemorrhages, two cases of acute exacerbation of ILD, and one of pneumonia. The
      sixth patient died of septic shock following septic arthritis of the knee.
      CONCLUSIONS: Lung complications can occur within months of initial anti-TNF
      treatment in older RA-ILD patients; therefore, anti-TNF therapy should be used
      with caution in these patients.

PMID- 25589844
TI  - A functioning adrenal adenoma and pheochromocytoma in the same adrenal gland: two
      discrete adrenal incidentalomas.

PMID- 25589845
TI  - An insulinoma with an aberrant feeder from the splenic artery detected by super
      selective arterial calcium stimulation with venous sampling.

PMID- 25589846
TI  - Extranodal natural killer/T-cell lymphoma of the tenosynovium of the hand.

PMID- 25589847
TI  - Occurrence of colonic liposarcoma after retroperitoneal liposarcoma.

PMID- 25589848
TI  - Dual ectopic thyroid presenting with an anterior neck mass.

PMID- 25589850
TI  - A new genus of soft coral (Cnidaria, Octocorallia) from the Republic of Congo
      (Pointe-Noire Region).
AB  - A new genus of soft coral from the Republic of Congo is described, Complexum gen.
      n. Nine West African octocoral species previously described in the genus
      Alcyonium by Tixier-Durivault (1955) are referred to this new genus, and a new
      species is described and figured, Complexumpusillum sp. n. The new species is
      characterized by having encrusting growth form and abundant spiny clubs in the
      surface of the polyparium. It colonizes shallow calcareous rocky banks (5 to 20 m
      depth) existing in coastal water of the region of Pointe-Noire. Based on
      molecular phylogeny this new genus is well separated from Alcyonium species. 

PMID- 25589851
TI  - A new genus and species of Thyasiridae (Mollusca, Bivalvia) from deep-water,
      Beaufort Sea, northern Alaska.
AB  - Bivalve mollusk shells were collected in 2350 m depth in the Beaufort Sea, Arctic
      Ocean off northern Alaska. Initial identification suggested the specimens were a
      member of the bivalve family Thyasiridae, but no known eastern Pacific or Arctic
      living or fossil thyasirid resembled these deep-water specimens. Comparisons were
      made with the type of the genera Maorithyas Fleming, 1950, Spinaxinus Oliver &
      Holmes, 2006, Axinus Sowerby, 1821, and Parathyasira Iredale, 1930. We determined
      the Beaufort Sea species represents a new genus, herein described as
      Wallerconcha. These specimens also represent a new species, herein named
      Wallerconchasarae. These new taxa are compared with known modern and fossil
      genera and species of thyasirds. 

PMID- 25589852
TI  - Four new species of the genus Saigona Matsumura (Hemiptera, Fulgoromorpha,
      Dictyopharidae) from China.
AB  - Four new species of the genus Saigona Matsumura, 1910, Saigonaanisomorpha Zheng,
      Yang & Chen, sp. n., Saigonadaozhenensis Zheng, Yang & Chen, sp. n.,
      Saigonadicondylica Zheng, Yang & Chen, sp. n. and Saigonatenuisa Zheng, Yang &
      Chen, sp. n., from China, are described and illustrated. A key to the species of
      Saigona is provided. 

PMID- 25589849
TI  - Rhupus syndrome.

PMID- 25589853
TI  - A new replacement name for Tropidocephalaspeciosa Ding, 2006 (Hemiptera,
      Fulgoromorpha, Delphacidae).
AB  - A new replacement name is proposed for the species Tropidocephalaspeciosa Ding,
      2006 (Hemiptera: Fulgoromorpha: Delphacidae: Tropidocephalini), preoccupied by
      Tropidocephalaspeciosa (Bierman, 1908): Tropidocephaladingi Sun, Yang & Chen,
      nom. n. = Tropidocephalaspeciosa Ding, 2006. The photographs and illustrations of
      this species are also provided. 

PMID- 25589854
TI  - Revision of the planthopper genus Nycheuma Fennah (Hemiptera, Fulgoromorpha,
      Delphacidae).
AB  - Chinese species in the genus Nycheuma Fennah, 1964a (Hemiptera: Fulgoromorpha:
      Delphacidae: Delphacinae: Delphacini) are revised to include three species:
      Nycheumacognatum (Muir, 1917), Nycheumadimorpha (Matsumura, 1910) and
      Nycheumanilotica Linnavuori, 1973. Nycheumacoctum Yang, 1989 is placed in
      synonymy with Nycheumanilotica Linnavuori, 1973. Nycheumadimorpha (Matsumura,
      1910) is newly recorded from China. The generic characteristics are redefined.
      The main morphological characters, male genitalia of 3 species are described or
      redescribed and illustrated. A key to Chinese species in the genus is provided. 

PMID- 25589856
TI  - Eucharitidae (Hymenoptera, Chalcidoidea), a family new to the fauna of Saudi
      Arabia, with the description of the previously unknown male of Eucharis
      (Psilogastrellus) affinis Boucek.
AB  - The family Eucharitidae (Hymenoptera: Chalcidoidea) is recorded for the first
      time for the fauna of Saudi Arabia based on Hydrorhoacaffra (Westwood) and
      Eucharis (Psilogastrellus) affinis Boucek. The record of Hydrorhoacaffra suggests
      that Al-Baha and Asir provinces should be considered as part of the Afrotropical
      rather than the Palaearctic region. The previously unknown male of
      Eucharisaffinis Boucek is described and figured. Macrophotographs of the species
      are provided. 

PMID- 25589857
TI  - Circanota: a new genus of Sparganothini from the Neotropics, and its two new
      species (Lepidoptera, Tortricidae).
AB  - Circanota, new genus, and its two new species, Circanotaundulata sp. n. (type
      species), from Costa Rica and Panama, and Circanotasimplex sp. n., from Panama
      and Ecuador, are described and illustrated. Although superficially similar to
      some species of Platynota Clemens, 1860, Circanota appears to be more closely
      related to members of a putative clade within Sparganothini defined by a slender
      crescent-shaped signum in the corpus bursae of the female genitalia. The most
      conspicuous autapomorphy for Circanota is the strongly undulate costa of the male
      and female forewing. Barcode sequence data (i.e., cytochrome oxidase I) from
      Circanotaundulata (n = 12) form a tight cluster with exceedingly limited genetic
      divergence (less than 0.1%); specimens of Circanotasimplex have not been
      sequenced. In neighbor-joining trees based on COI, Circanota is portrayed nearest
      Sparganothoides, which is consistent with morphological evidence. 

PMID- 25589855
TI  - Species delimitation using morphology, morphometrics, and molecules: definition
      of the Ophionscutellaris Thomson species group, with descriptions of six new
      species (Hymenoptera, Ichneumonidae).
AB  - The diverse genus Ophion is almost entirely undescribed in the Nearctic region.
      In this paper we define the Ophionscutellaris species group. This species group
      is well-supported by analysis of DNA (ITS2, COI, and 28S D2-D3) and morphology.
      It includes the Palearctic species Ophionscutellaris and the Nearctic species
      Ophionidoneus. An integrative analysis of DNA, geometric wing morphometrics,
      classical morphometrics and qualitative morphology indicates that this species
      group contains a minimum of seven species in North America, although the full
      diversity of the group has likely not been sampled. Ophionclave Schwarzfeld, sp.
      n., Ophionaureus Schwarzfeld, sp. n., Ophionbrevipunctatus Schwarzfeld, sp. n.,
      Ophiondombroskii Schwarzfeld, sp. n., Ophionkeala Schwarzfeld, sp. n. and
      Ophionimportunus Schwarzfeld, sp. n. are described, and a key to the known
      Nearctic species of the Ophionscutellaris group is provided. 

PMID- 25589858
TI  - Salmokottelati, a new species of trout from Alakir Stream, draining to the
      Mediterranean in southern Anatolia, Turkey (Teleostei, Salmonidae).
AB  - Salmokottelati sp. n., is described from Alakir Stream (Mediterranean basin) in
      Turkey. It is distinguished from other Anatolian Salmo species by a combination
      of the following characters (none unique to the species): general body colour
      greenish to silvery in life; 7-9 parr marks along lateral line; four dark bands
      on flank absent in both sexes; black ocellated spots few, present only on upper
      part of flank in individuals smaller than 160 mm SL but in larger both males and
      females black spots numerous and located on back and middle and upper part of
      flank; red spots few to numerous, scattered on median, and half of lower and
      upper part of flank; head long (length 29-33% SL in males, 26-32 in females);
      mouth large (length of mouth gape 13-19% SL in males, 12-15 in females); maxilla
      long (length 10-13% SL in males, 8-12 in females); 105-113 lateral line scales;
      24-29 scale rows between lateral line and dorsal-fin origin, 17-19 scale rows
      between lateral line and anal-fin origin; 13-15 scales between lateral line and
      adipose-fin insertion. 

PMID- 25589859
TI  - Three new species of mygalomorph and filistatid spiders from Iran (Araneae,
      Cyrtaucheniidae, Nemesiidae and Filistatidae).
AB  - Three new spider species are described from Iran: Anemesiakoponeni sp. n. (?,
      Cyrtaucheniidae); Raveniolamazandaranica sp. n. (?, Nemesiidae) and
      Sahastatasinuspersica sp. n. (?, Filistatidae). Cyrtaucheniidae and Sahastata
      Benoit, 1968 are reported from Iran for the fisrt time. 

PMID- 25589860
TI  - A new Eastern Asian Hycleus and key to the Chinese species of the phaleratus
      group (Coleoptera, Meloidae, Mylabrini).
AB  - A new species of Hycleus belonging to the phaleratus group, and close to
      Hycleusphaleratus, is described. The new species, Hycleusmarcipoli, is
      distributed in China (Gansu and Taiwan), Laos, and northern Thailand. A key to
      the Chinese species of this group is presented. 

PMID- 25589861
TI  - Contribution to the knowledge of the Carabus (Archiplectes) satyrus Kurnakov,
      1962, species complex in Abkhazia (Coleoptera, Carabidae, Carabini).
AB  - This study is based on a comparative analysis of extensive material of Carabus
      (Archiplectes) satyrus Kurnakov, 1962, its various forms and related taxa
      recently collected by the authors and some other collectors in Abkhazia. The
      status or specific affiliations of several subspecies are changed and a
      subspecies is described. Carabus (Archiplectes) besleticus Kurnakov, 1972, stat.
      n. is treated as a separate species housing six hitherto established subspecies
      in addition to the nominal type: Carabus (Archiplectes) besleticusmtsaranus
      Kurnakov, 1972, Carabus (Archiplectes) besleticusduripshensis Kurnakov, 1972,
      Carabus (Archiplectes) besleticusnapraensis Belousov & Zamotajlov, 1993, Carabus
      (Archiplectes) besleticusdsychvensis Kurnakov, 1972, Carabus (Archiplectes)
      besleticusadzinbai Retezar, 2013, and Carabus (Archiplectes)
      besleticusresheviensissubsp. n.Carabus (Archiplectes) satyrus is treated as
      monotypical while the specific status of Carabus (Archiplectes) pseudopshuensis
      Zamotajlov, 1991, earlier proposed by Fominykh and Zamotajlov (2012), is
      confirmed based on the morphological and morphometric data. 

PMID- 25589862
TI  - Revision of Chaetocnemasemicoerulea species-group (Coleoptera, Chrysomelidae,
      Galerucinae, Alticini) in China, with descriptions of three new species.
AB  - Chinese species of Chaetocnemasemicoerulea group are revised and three new
      species described as new: Chaetocnemasalixis sp. n., Chaetocnemayulongensis sp.
      n. and Chaetocnemadeqinensis sp. n.. A key to all five species of this group
      occurring in China and the illustrations of habitus and genitalia are provided. A
      map of species distribution is given. 

PMID- 25589863
TI  - Bembidion (?Nipponobembidion) ruruy sp. n., a new brachypterous ground beetle
      (Coleoptera, Carabidae) from Kunashir Island, Kuriles, Russia.
AB  - A new species, Bembidion (?Nipponobembidion) ruruysp. n., is described from the
      foot of Ruruy Volcano, Kunashir Island, Kuril Archipelago, Russia. It is only the
      second consubgener, being characterized by the reduced wings, the rounded elytral
      shoulders, and the backward position of the posterior supra-orbital pore. In this
      connection, the subgenus Nipponobembidion Habu & Baba, 1968 is rediagnosed and
      both of its species are keyed. It might have originated from Plataphodes
      Ganglbauer, 1891, possibly in relation to volcanic activities in the region. 

PMID- 25589864
TI  - When DNA barcoding and morphology mesh: Ceratopogonidae diversity in Finnmark,
      Norway.
AB  - DNA barcoding in Ceratopogonidae has been restricted to interpreting the
      medically and veterinary important members of Culicoides Latreille. Here the
      technique is utilised, together with morphological study, to interpret all
      members of the family in a select area. Limited sampling from the county of
      Finnmark in northernmost Norway indicated the presence of 54 species, including
      14 likely new to science, 16 new to Norway, and one new to Europe. No species
      were previously recorded from this county. Only 93 species were known for all of
      Norway before this survey, indicating how poorly studied the group is. We
      evaluate and discuss morphological characters commonly used in identification of
      biting midges and relate species diagnoses to released DNA barcode data from 223
      specimens forming 58 barcode clusters in our dataset. DNA barcodes and morphology
      were congruent for all species, except in three morphological species where
      highly divergent barcode clusters indicate the possible presence of cryptic
      species. 

PMID- 25589865
TI  - The LifeWatch approach to the exploration of distributed species information.
AB  - This paper introduces a new method of automatically extracting, integrating and
      presenting information regarding species from the most relevant online taxonomic
      resources. First, the information is extracted and joined using data wrappers and
      integration solutions. Then, an analytical tool is used to provide a visual
      representation of the data. The information is then integrated into a user
      friendly content management system. The proposal has been implemented using data
      from the Global Biodiversity Information Facility (GBIF), the Catalogue of Life
      (CoL), the World Register of Marine Species (WoRMS), the Integrated Taxonomic
      Information System (ITIS) and the Global Names Index (GNI). The approach improves
      data quality, avoiding taxonomic and nomenclature errors whilst increasing the
      availability and accessibility of the information. 

PMID- 25589866
TI  - Focus stacking: Comparing commercial top-end set-ups with a semi-automatic low
      budget approach. A possible solution for mass digitization of type specimens.
AB  - In this manuscript we present a focus stacking system, composed of commercial
      photographic equipment. The system is inexpensive compared to high-end commercial
      focus stacking solutions. We tested this system and compared the results with
      several different software packages (CombineZP, Auto-Montage, Helicon Focus and
      Zerene Stacker). We tested our final stacked picture with a picture obtained from
      two high-end focus stacking solutions: a Leica MZ16A with DFC500 and a Leica
      Z6APO with DFC290. Zerene Stacker and Helicon Focus both provided satisfactory
      results. However, Zerene Stacker gives the user more possibilities in terms of
      control of the software, batch processing and retouching. The outcome of the test
      on high-end solutions demonstrates that our approach performs better in several
      ways. The resolution of the tested extended focus pictures is much higher than
      those from the Leica systems. The flash lighting inside the Ikea closet creates
      an evenly illuminated picture, without struggling with filters, diffusers, etc.
      The largest benefit is the price of the set-up which is approximately ? 3,000,
      which is 8 and 10 times less than the LeicaZ6APO and LeicaMZ16A set-up
      respectively. Overall, this enables institutions to purchase multiple solutions
      or to start digitising the type collection on a large scale even with a small
      budget. 

PMID- 25589867
TI  - Three species of Hitobia Kamura, 1992 (Araneae, Gnaphosidae) from south-west
      China.
AB  - Two new species and one new record of the Hitobia are described from Gaoligong
      Mountains, Yunnan Province, China: Hitobiatengchong sp. n. (male),
      Hitobiahirtella sp. n. (male) and Hitobiamakotoi Kamura, 2011. Distributional
      data and illustrations of body and copulatory organs are provided. The
      differences between the new species and their related species are discussed. 

PMID- 25589868
TI  - A new species of tiger beetle from southeastern Arizona and Mexico (Coleoptera,
      Carabidae, Cicindelini).
AB  - A new tiger beetle species, Cicindelidiamelissa Duran & Roman, sp. n., of the
      tribe Cicindelini, is described from high elevation montane forests of
      southeastern Arizona and Mexico. It appears to be most closely related to
      Cicindelidianebuligera (Bates) but is distinguished on the basis of multiple
      morphological characters and geographic range. The new species is also
      superficially similar to the widespread Cicindelidiasedecimpunctata (Klug), but
      distinguished on the basis of multiple morphological characters and habitat.
      Habitus, male and female reproductive structures, and known distribution map are
      presented. 

PMID- 25589869
TI  - Two new species of Myrmedonota Cameron (Staphylinidae, Aleocharinae) from Mexico.
AB  - Two new species of Myrmedonota are described from Mexico. Illustrations and a
      distribution map are provided, as are keys to identify Myrmedonota known from the
      Nearctic and Neotropics. Specimens were collected by means of mercury vapor light
      traps or flight interception traps. 

PMID- 25589870
TI  - A new species and synonymy of the Neotropical Eucelatoria Townsend and
      redescription of Myiodoriops Townsend.
AB  - The New World tropics represents the most diverse region for tachinid parasitoids
      (Diptera: Tachinidae), but it also contains the most narrowly defined, and
      possibly the most confusing, tachinid genera of any biogeographic region. This
      over-splitting of genera and taxonomic confusion has limited progress toward our
      understanding the family in this region and much work is needed to revise,
      redefine, and make sense of the profusion of finely split taxa. In a recent
      analysis of the Neotropical genus Erythromelana Townsend, two species previously
      assigned to this genus, Euptilodegeeriaobumbrata (Wulp) and Myiodoriopsmarginalis
      Townsend were reinstated as monotypic genera. In the present study, we
      demonstrate that Euptilodegeeriaobumbrata (Wulp), previously assigned to three
      different genera, represents in fact a species of the large New World genus
      Eucelatoria Townsend, in which females possess a sharp piercer for oviposition.
      We also show that the species Eucelatoriacarinata (Townsend) belongs to the same
      species group as Eucelatoriaobumbrata, which we here define and characterize as
      the Eucelatoriaobumbrata species group. Additionally, we describe
      Eucelatoriaflava sp. n. as a new species within the Eucelatoriaobumbrata species
      group. Finally, we redescribe the genus Myiodoriops Townsend and the single
      species Myiodoriopsmarginalis Townsend. 

PMID- 25589871
TI  - Taxonomic study of the genus Halolaguna Gozmany (Lepidoptera, Lecithoceridae)
      from China, with descriptions of two new species.
AB  - The genus Halolaguna Gozmany, 1978 is studied in China. Two new species,
      Halolagunaflabellata sp. n. from Guangxi and Halolagunadiscoidea sp. n. from
      Chongqing, Guangxi and Sichuan are described. The female of
      Halolagunaguizhouensis Wu, 2012 is reported for the first time. Photographs of
      adults and genitalia are provided. A checklist of all known Halolaguna species is
      included, along with a key to the Chinese species. 

PMID- 25589872
TI  - The origin and early evolution of metatherian mammals: the Cretaceous record.
AB  - Metatherians, which comprise marsupials and their closest fossil relatives, were
      one of the most dominant clades of mammals during the Cretaceous and are the most
      diverse clade of living mammals after Placentalia. Our understanding of this
      group has increased greatly over the past 20 years, with the discovery of new
      specimens and the application of new analytical tools. Here we provide a review
      of the phylogenetic relationships of metatherians with respect to other mammals,
      discuss the taxonomic definition and diagnosis of Metatheria, outline the
      Cretaceous history of major metatherian clades, describe the paleobiology,
      biogeography, and macroevolution of Cretaceous metatherians, and provide a
      physical and climatic background of Cretaceous metatherian faunas. Metatherians
      are a clade of boreosphendian mammals that must have originated by the Late
      Jurassic, but the first unequivocal metatherian fossil is from the Early
      Cretaceous of Asia. Metatherians have the distinctive tightly interlocking
      occlusal molar pattern of tribosphenic mammals, but differ from Eutheria in their
      dental formula and tooth replacement pattern, which may be related to the
      metatherian reproductive process which includes an extended period of lactation
      followed by birth of extremely altricial young. Metatherians were widespread over
      Laurasia during the Cretaceous, with members present in Asia, Europe, and North
      America by the early Late Cretaceous. In particular, they were taxonomically and
      morphologically diverse and relatively abundant in the Late Cretaceous of western
      North America, where they have been used to examine patterns of biogeography,
      macroevolution, diversification, and extinction through the Late Cretaceous and
      across the Cretaceous-Paleogene (K-Pg) boundary. Metatherian diversification
      patterns suggest that they were not strongly affected by a Cretaceous Terrestrial
      Revolution, but they clearly underwent a severe extinction across the K-Pg
      boundary. 

PMID- 25589873
TI  - Distribution and habitat of the Laotian Rock Rat Laonastesaenigmamus Jenkins,
      Kilpatrick, Robinson & Timmins, 2005 (Rodentia: Diatomyidae) in Vietnam.
AB  - The Laotian Rock Rat Laonastesaenigmamus Jenkins, Kilpatrick, Robinson & Timmins,
      2005 was originally discovered in Lao People's Democratic Republic in 2005. This
      species has been recognized as the sole surviving member of the otherwise extinct
      rodent family Diatomyidae. Laonastesaenigmamus was initially reported only in
      limestone forests of Khammouane Province, Central Lao. A second population was
      recently discovered in Phong Nha Ke Bang National Park (PNKB NP), Quang Binh
      Province, Central Vietnam in 2011. The confirmed distribution range of
      L.aenigmamus in Vietnam is very small, approximately 150 km(2), covering low
      karst mountains in five communes of Minh Hoa District, Quang Binh Province, at
      elevations between 250 and 400 m asl. The Laotian Rock Rat inhabits the lower
      part of steep karst towers with many rock boulders and crevices under tall
      limestone evergreen forest. They use small rock crevices for their dens. The
      natural habitat of this species in PNKB NP has been affected by selected timber
      harvesting, however, a complex 3-4 layer forest structure is retained. The
      Laotian Rock Rat is omnivorous, feeding on parts (leaves, buds, fruits and roots)
      of 18 plant species and also some insects (cicada, mantis, grasshopper). The
      population of this species in PNKB NP is seriously threatened with extinction due
      to its very restricted distribution, high hunting pressure, and habitat
      disturbance. Laonastesaenigmamus is listed in the IUCN Red List as endangered and
      in the Wildlife and Aquatic Red List of Lao, however, this species has not been
      listed in the Red Data Book or any conservation legislative documents of Vietnam.

PMID- 25589874
TI  - New synonym of Tipula (Vestiplex) wahlgrenana Alexander, 1968 (Diptera:
      Tipulidae).
AB  - Based on examination of type specimens a crane fly species Tipula (Vestiplex)
      hugueniniana Alexander, 1971 is proposed as junior synonym of Tipula (V.)
      wahlgrenana Alexander, 1968. The new synonymy is based on similarity of male
      genitalia. 

PMID- 25589875
TI  - An occurence records database of French Guiana harvestmen (Arachnida, Opiliones).
AB  - This dataset provides information on specimens of harvestmen (Arthropoda,
      Arachnida, Opiliones) collected in French Guiana. Field collections have been
      initiated in 2012 within the framework of the CEnter for the Study of
      Biodiversity in Amazonia (CEBA: www.labex-ceba.fr/en/). This dataset is a work in
      progress.  Occurrences are recorded in an online database stored at the EDB
      laboratory after each collecting trip and the dataset is updated on a monthly
      basis. Voucher specimens and associated DNA are also stored at the EDB laboratory
      until deposition in natural history Museums. The latest version of the dataset is
      publicly and freely accessible through our Integrated Publication Toolkit at
      http://130.120.204.55:8080/ipt/resource.do?r=harvestmen_of_french_guiana or
      through the Global Biodiversity Information Facility data portal at
      http://www.gbif.org/dataset/3c9e2297-bf20-4827-928e-7c7eefd9432c. 

PMID- 25589876
TI  - On the female of Gyponareversa DeLong & Martinson, 1972, with emphasis on genital
      structures (Insecta: Hemiptera: Cicadellidae).
AB  - Gyponareversa DeLong & Martinson, 1972 has its ovipositor described and
      illustrated based on the examination of specimens from its type locality. This is
      the first species of Gypona Germar, 1821 to have the female genitalia detailed
      description published. 

PMID- 25589877
TI  - Vignayadavii (Leguminosae: Papilionoideae), a new species from Western Ghats,
      India.
AB  - A new species of Vigna Savi, subgenus Ceratotropis (Piper) Verdc., Vignayadavii
      S.P. Gaikwad, R.D. Gore, S.D. Randive & K.U. Garad, sp. nov. is described and
      illustrated here. It is morphologically close to Vignadalzelliana (Kuntze) Verdc.
      but differs in its underground obligate cleistogamous flowers on positively
      geotropic branches, hairy calyx, small corolla, linear style beak and dimorphic
      seeds with shiny seed coat. 

PMID- 25589879
TI  - Isolation of acanthamoeba genotype t4 from a non-contact lens wearer from the
      Philippines.
AB  - We report the case of a 76-year old Filipino male who presented with pain,
      redness, and blurring of vision of the right eye. Corneal scraping was done and
      sent to the St. Luke's Research and Biotechnology Group for detection and
      identification of the infectious agent. Morphological detection was performed by
      allowing the organism from the scraping to grow in 1.5% non-nutrient agar plate
      with heat-killed E. coli. Trophozoites with acanthopodia and double-walled cysts
      characteristic of Acanthamoeba were observed within the first and second week of
      observations, respectively. Molecular identification of the amoebae at the genus
      level based on the presence of Acanthamoeba-specific amplimer S1, ASA.S1
      confirmed the morphological identification. Genotyping through sequence revealed
      that the organism belonged to T4, which is the genotype commonly present in the
      eye of keratitis patients. 

PMID- 25589878
TI  - The association of cytokines with severe dengue in children.
AB  - BACKGROUND: Dengue virus infection is a major public health problem. A hypothesis
      put forward for severe dengue is the cytokine storm, a sudden increase in
      cytokines that induces vascular permeability. Previous studies and our recent
      meta-analysis showed that IL-6, IL-8, IFNgamma, TNFalpha, VEGF-A and VCAM-1 are
      associated with dengue shock syndrome. Therefore, in this study we aim to
      validate the association of these cytokines with severe dengue. METHODS &
      FINDINGS: In a hospital based-case control study in Vietnam, children with dengue
      fever, other febrile illness and healthy controls were recruited. Dengue virus
      infection was confirmed by several diagnostic tests. Multiplex immunoassay using
      Luminex technology was used to measure cytokines simultaneously. A positive
      association with dengue shock syndrome was found for VCAM-1, whereas a negative
      association was found for IFNgamma. Furthermore, multivariate logistic analysis
      also showed that VCAM-1 and IFNgamma were independently correlated with dengue
      shock syndrome. CONCLUSION: IFNgamma and VCAM-1 were associated with dengue shock
      syndrome, although their role in the severe dengue pathogenesis remains unclear.
      Additional studies are required to shed further light on the function of these
      cytokines in severe dengue.

PMID- 25589880
TI  - Sand fly fauna (Diptera, pcychodidae, phlebotominae) in different leishmaniasis
      endemic areas of ecuador, surveyed using a newly named mini-shannon trap.
AB  - To study the sand fly fauna, surveys were performed at four different
      leishmaniasis-endemic sites in Ecuador from February 2013 to April 2014. A
      modified and simplified version of the conventional Shannon trap was named "mini
      Shannon trap" and put to multiple uses at the different study sites in limited,
      forested and narrow spaces. The mini-Shannon, CDC light trap and protected human
      landing method were employed for sand fly collection. The species identification
      of sand flies was performed mainly based on the morphology of spermathecae and
      cibarium, after dissection of fresh samples. In this study, therefore, only
      female samples were used for analysis. A total of 1,480 female sand flies
      belonging to 25 Lutzomyia species were collected. The number of female sand flies
      collected was 417 (28.2%) using the mini-Shannon trap, 259 (17.5%) using the CDC
      light trap and 804 (54.3%) by human landing. The total number of sand flies per
      trap collected by the different methods was markedly affected by the study site,
      probably because of the various composition of species at each locality.
      Furthermore, as an additional study, the attraction of sand flies to mini-Shannon
      traps powered with LED white-light and LED black-light was investigated
      preliminarily, together with the CDC light trap and human landing. As a result, a
      total of 426 sand flies of nine Lutzomyia species, including seven man-biting and
      two non-biting species, were collected during three capture trials in May and
      June 2014 in an area endemic for leishmaniasis (La Ventura). The black-light
      proved relatively superior to the white-light with regard to capture numbers, but
      no significant statistical difference was observed between the two traps. 

PMID- 25589881
TI  - BSL-3 Laboratory User Training Program at NUITM-KEMRI.
AB  - Pathogens handled in a Biosafety Level 3 (BSL-3) containment laboratory pose
      significant risks to laboratory staff and the environment. It is therefore
      necessary to develop competency and proficiency among laboratory workers and to
      promote appropriate behavior and practices that enhance safety through biosafety
      training. Following the installation of our BSL-3 laboratory at the Center for
      Microbiology Research-Kenya Medical Research Institute in 2006, a biosafety
      training program was developed to provide training on BSL-3 safety practices and
      procedures. The training program was developed based on World Health Organization
      specifications, with adjustments to fit our research activities and biosafety
      needs. The program is composed of three phases, namely initial assessment, a
      training phase including theory and a practicum, and a final assessment. This
      article reports the content of our training program. 

PMID- 25589883
TI  - Epidermodysplasia Verruciformis-like Skin Eruption in an HIV-positive Patient.
AB  - Epidermodysplasia Verruciformis-like skin eruption is a rare syndrome that
      usually occurs in patients with immunodeficiency, predisposing them to infections
      with human papilloma beta virus (HPV). We report here an HIV patient presenting
      with this syndrome. 

PMID- 25589882
TI  - Human Cystic Echinococcosis in the Nalut District of Western Libya: A Clinico
      epidemiological Study.
AB  - Human cystic echinococcosis (CE) is an endemic disease in the Mediterranean area
      that has not yet been fully documented in western Libya. The present study
      describes the clinico-epidemiologic profile of CE in western Libya's Nalut
      district. From April 2008 to July 2011, 36 cases of CE were confirmed following
      surgical removal of cysts. The cysts were most frequently found in the liver
      (61.1%), followed by the lungs (19.4%), kidneys (11.1%), peritoneal cavity
      (11.1%), and spleen (5.6%). Among the 36 patients, 6 possessed plural cysts and 3
      had cysts in 2 organs. Blood samples from this group were examined for the
      presence of serum anti-hydatid IgG antibodies, which revealed positivity in 25
      patients (69.4%). An additional 300 blood samples were collected randomly from
      the inpatient and outpatient clinics at Nalut Hospital. Twenty-seven samples (9%)
      were found to be positive for the anti-hydatid IgG antibody among which the
      prevalence of infection tended to be higher in men (12%) than in women (6%). This
      study demonstrates that CE is a major parasitic infectious disease of public
      health significance in Libya, notably in the western part of the country, and
      that disease awareness needs to be raised nationwide. 

PMID- 25589884
TI  - Ovipositional Behavior of Anopheles gambiae Mosquitoes.
AB  - Mosquito eggs laid within two hours are necessary for transgenic (injection)
      studies, because mosquito eggs become hard after that period. Thus, in order to
      have eggs available within this two-hour window, it is important to understand
      the ovipositional behavior of Anopheles gambiae s.s.. In the present study, the
      ovipositional behavior of An. gambiae s.s. (Kisumu) was investigated in several
      different conditions: age of mosquitoes, time post blood meal to access
      oviposition substrate, and light conditions. Two groups of mosquitoes, 3-5 days
      old and 9-11 days old were blood-fed. For those mosquito groups, an oviposition
      dish was set either at 48 hours or 72 hours after the blood meal either in a
      light condition or in an artificial dark condition. The number of laid eggs was
      compared among the different conditions. The 3-5 day-old mosquitoes apparently
      produced a higher number of eggs than 9-11 day-old mosquitoes, while there was no
      significant difference between the two groups. The number of laid eggs per one
      surviving blood-fed mosquito in the dark condition was significantly higher than
      that in the light condition (p = 0.03). Providing an oviposition dish at 72 hours
      after blood meal resulted in a significantly higher number of laid eggs per one
      surviving blood-fed mosquito than at 48 hours after blood meal (p = 0.03). In
      conclusion, the optimal condition to have readily available egg supply for
      transgenic analysis was as follows: 3-5 day-old mosquitoes with an oviposition
      dish placed at 72 hours after the blood meal in a dark environment. 

PMID- 25589885
TI  - Syndecan-1 expression is associated with tumor size and EGFR expression in
      colorectal carcinoma: a clinicopathological study of 230 cases.
AB  - BACKGROUND: Syndecan-1 (SDC1) is reported to modulate several key processes of
      tumorigenesis and has variable expression in many cancers. To date, the cause of
      altered expression has not been elucidated. In this study, we compared SDC1
      expression with various clinicopathological parameters and molecular markers to
      evaluate its clinical significance in colorectal carcinoma. METHODS: We screened
      for SDC1 expression using immunohistochemistry in 230 surgical specimens of
      primary colorectal carcinoma from patients consecutively treated between 2008 and
      2011 at Seoul St. Mary's Hospital, The Catholic University of Korea. The
      relationship between SDC1 expression and various clinicopathological parameters
      and molecular markers was analyzed. RESULTS: The tumors were principally located
      in the left colon (71.3%) and rectum (33.5%). There were 216 (93.9%)
      adenocarcinomas, 10 (4.3%) mucinous adenocarcinomas, and 4 other tumors. Most of
      the carcinomas were pT3 (68.3%) and pT4 (22.2%). There was regional lymph node
      metastasis in 140 patients. SDC1 expression was identified in the cancer cells of
      212 (96.8%) colon cancer cases. Of the SDC1-positive cases, 131 showed
      predominantly membranous immunopositivity, and 81 showed a predominantly
      cytoplasmic staining pattern. Mixed membranous and cytoplasmic staining was
      observed in 154 cases. In 93 cases, stromal SDC1 reactivity was noted. Epithelial
      SDC1 immunopositivity was significantly associated with tumor size (p=0.016) and
      epidermal growth factor receptor expression (p=0.006). However, it was not
      significantly correlated with lymph node metastasis, distant metastasis,
      lymphatic or vascular invasion, or KRAS mutation. In addition, stromal SDC1
      immunopositivity was significantly associated with the male sex (p=0.018).
      CONCLUSIONS: The expression profile of SDC1 may be of clinical value in
      colorectal cancer and may help in identifying aggressive forms of colorectal
      carcinoma. Further studies are needed in order to better understand the role of
      SDC1 in the progression and invasiveness of colorectal carcinoma.

PMID- 25589887
TI  - Effect of the hand antiseptic agents benzalkonium chloride, povidone-iodine,
      ethanol, and chlorhexidine gluconate on atopic dermatitis in NC/Nga mice.
AB  - Antiseptic agents can cause skin irritation and lead to severe problems,
      especially for individuals with atopic diatheses. We investigated the effect of 4
      different antiseptic agents using an atopic dermatitis (AD) model mouse. NC/Nga
      mice were subcutaneously injected with mite allergen (Dp) to induce AD-like skin
      lesions (ADSLs), and an application of 0.2% (w/v) benzalkonium chloride (BZK),
      10% (w/v) povidone-iodine (PVP-I), 80% (v/v) ethanol (Et-OH), or 0.5% (v/v)
      chlorhexidine gluconate (CHG) was applied to the ear envelope. BZK induced a
      significant increase in the severity of the clinical score, infiltration of
      inflammatory cells, local expression of inflammatory cytokines in subcutaneous
      tissue, and total serum immunoglobulin (Ig) E. PVP-I increased the clinical
      score, number of mast cells, and production of inflammatory cytokines, and total
      serum IgE. Et-OH increased the clinical score and number of inflammatory cells,
      but showed no effect on serum IgE levels. No differences in any parameters were
      observed between CHG and the vehicle. Collectively, the results suggest the
      severity of the ADSL was related in part to the strength of the immunoreaction.
      These findings suggest that CHG could offer the lowest risk of inducing ADSL in
      individuals with atopic dermatitis and that medical staff and food handlers with
      AD could benefit from its use. 

PMID- 25589888
TI  - Single nucleotide polymorphism in Ag85 genes of Mycobacterium tuberculosis
      complex: analysis of 178 clinical isolates from China and 13 BCG strains.
AB  - Host immune pressure and associated immune evasion of pathogenic bacteria are key
      features of host-pathogen co-evolution. Human T-cell epitopes of Mycobacterium
      tuberculosis (M. tuberculosis) were evolutionarily hyperconserved and thus it was
      deduced that M. tuberculosis lacks antigenic variation and immune evasion.
      However, in our previous studies, proteins MPT64, PstS1, Rv0309 and Rv2945c all
      harbored higher numbers of amino acid substitutions in their T cell epitopes,
      which suggests their roles in ongoing immune evasion. Here, we used the same set
      of 180 clinical M. tuberculosis complex (MTBC) isolates from China, amplified the
      genes encoding Ag85 complex, and compared the sequences. The results showed that
      Ag85 were hyperconserved in T/B cell epitopes and the genes were more likely to
      be under purifying selection. The divergence of host immune selection on
      different proteins may result from different function of the proteins. In
      addition, A312G of Ag85A and T418C of Ag85B may represent special mutations in
      BCG strains, which may be used to differentiate M.bovis and BCG strains from MTB
      strains. Also, C714A in Ag85B seems to be a valuable phylogenetic marker for
      Beijing strains. 

PMID- 25589890
TI  - Malignant lymphomas in the head and neck region--a retrospective, single-center
      study over 41 years.
AB  - OBJECTIVES: Non-Hodgkin lymphomas are malignant neoplastic proliferations of the
      immune system that can manifest as nodal or extranodal lymphomas. The aim of this
      study was to retrospectively investigate the site of occurrence of lymphomas in
      the head and neck area and to analyze the typical symptoms of patients who
      presented at an oral and maxillofacial surgical department. MATERIAL AND METHODS:
      All patient files from 1971 until 2012 from an Oral and Maxillofacial Surgery of
      a University were analyzed for the diagnosis non-Hodgkin lymphoma. Epidemiologic
      data and data regarding the localization of the malignant lymphoma were
      evaluated. RESULTS: 62 patients, 34 women and 28 men with a non-Hodgkin lymphoma
      in the head and neck area were treated in the 41 years analyzed. In 87% of the
      cases the lymphoma belonged to B-cell and in 12% to the T-cell lineage. The
      average age at the time of diagnosis was 67 years for women (n=34) and 56 years
      for men. With 22 patients each, the non-Hodgkin lymphoma was localized in either
      the soft tissues or osseous structures. In the remaining 18 cases, multiple
      structures were affected. In 33 patients no accompanying nodal manifestation was
      noticed. In 33 cases the lymphoma was located in the oral cavity. The most common
      symptoms were swelling (97%), pain (40%) and the existence of an ulcer (11%).
      CONCLUSION: In the present study more than 50% of the lymphomas were located in
      the oral cavity. Due to the unspecific symptoms, a histopathological verification
      of the diagnosis is crucial.

PMID- 25589891
TI  - Utility of kynurenic acid for non-invasive detection of metastatic spread to
      lymph nodes in non-small cell lung cancer.
AB  - BACKGROUND: Kynurenic acid (KYNA) is a side-stream product of the kynurenine
      metabolic pathway that plays a controversial role in malignancies either enabling
      escape of malignant cells from immune surveillance or exerting antiproliferative
      effect on cancer cells, and is associated with differences in invasiveness
      related to metastatic spread to lymph nodes in lung cancer. Nodal involvement is
      a significant negative prognostic factor usually considered a contraindication
      for primary surgical resection. OBJECTIVE: To assess potential value of
      circulating KYNA for non-invasive identification of patients with metastatic
      lymph nodes (N+) in non-small cell lung cancer (NSCLC). METHODS: KYNA level in
      venous blood serum was determined with use of high performance liquid
      chromatography (HPLC) in 312 subjects including 230 patients with NSCLC and 32
      healthy controls. RESULTS: Circulating KYNA level in NSCLC patients was higher
      than in controls (93.6+/-61.9 pmol/ml vs. 31.4+/-16.6 pmol/ml; p=2.2*10(-15)) and
      positively correlated with N (R=0.326; p=2*(10-6)) but not with T or M stage
      (p>0.05). In N+ patients it was higher than in N0 patients (137.7+/-51.8 pmol/ml
      vs. 71.9+/-41.7 pmol/ml; p=4.8*10(-16)). KYNA effectively discriminated N+ from
      N0 patients at a cut-off value 82.3 pmol/ml with sensitivity 94.7% (95%CI 87.1
      98.5%), specificity 80.5% (95%CI 73.4-86.5%), negative predictive value
      NPV=96.8%, PPV=70.5% and area under the ROC curve AUC=0.900 (95%CI 0.854-0.935;
      p=0.0001). DISCUSSION AND CONCLUSION: Circulating KYNA level measurement offers
      reliable non-invasive discrimination between N0 and N+ patients in NSCLC. Robust
      discriminatory characteristics of KYNA assay predestines it for clinical use as
      an adjunct facilitating selection of candidates for primary surgical resection.

PMID- 25589886
TI  - Liver function parameters in hip fracture patients: relations to age, adipokines,
      comorbidities and outcomes.
AB  - AIM: To asses liver markers in older patients with hip fracture (HF) in relation
      to age, comorbidities, metabolic characteristics and short-term outcomes.
      METHODS: In 294 patients with HF (mean age 82.0+/-7.9 years, 72.1% women) serum
      alanine aminotransferase (ALT), gammaglutamyltransferase (GGT), alkaline
      phosphatase (ALP), albumin, bilirubin, 25(OH)vitaminD, PTH, calcium, phosphate,
      magnesium, adiponectin, leptin, resistin, thyroid function and cardiac troponin I
      were measured. RESULTS: Elevated ALT, GGT, ALP or bilirubin levels on admission
      were observed in 1.7%-9.9% of patients. With age GGT, ALT and leptin decrease,
      while PTH and adiponectin concentrations increase. Higher GGT (>30 U/L, median
      level) was associated with coronary artery disease (CAD), diabetes mellitus (DM),
      and alcohol overuse; lower ALT (<=20 U/L, median level) with dementia; total
      bilirubin>20 MUmol/L with CAD and alcohol overuse; and albumin>33 g/L with CAD.
      Multivariate adjusted regression analyses revealed ALT, ALP, adiponectin, alcohol
      overuse and DM as independent and significant determinants of GGT (as continuous
      or categorical variable); GGT for each other liver marker; and PTH for
      adiponectin. The risk of prolonged hospital stay (>20 days) was about two times
      higher in patients with GGT>30 U/L or adiponectin>17.14 ng/L (median level) and
      4.7 times higher if both conditions coexisted. The risk of in-hospital death was
      3 times higher if albumin was <33 g/L. CONCLUSIONS: In older HF patients liver
      markers even within the normal range are associated with age-related disorders
      and outcomes. Adiponectin (but not 25(OH)vitaminD, PTH, leptin or resistin) is an
      independent contributor to higher GGT. Serum GGT and albumin predict prolonged
      hospital stay and in-hospital death, respectively. A unifying hypothesis of the
      findings presented.

PMID- 25589889
TI  - Antipsychotics-associated serious adverse events in children: an analysis of the
      FAERS database.
AB  - OBJECTIVE: The reports submitted to the US Food and Drug Administration (FDA)
      Adverse Event Reporting System (FAERS) from 1997 to 2011 were reviewed to assess
      serious adverse events induced by the administration of antipsychotics to
      children. METHODS: Following pre-processing of FAERS data by elimination of
      duplicated records as well as adjustments to standardize drug names, reports
      involving haloperidol, olanzapine, quetiapine, clozapine, ziprasidone,
      risperidone, and aripiprazole were analyzed in children (age 0-12). Signals in
      the data that signified a drug-associated adverse event were detected via
      quantitative data mining algorithms. The algorithms applied to this study include
      the empirical Bayes geometric mean, the reporting odds ratio, the proportional
      reporting ratio, and the information component of a Bayesian confidence
      propagation neural network. Neuroleptic malignant syndrome (NMS), QT
      prolongation, leukopenia, and suicide attempt were focused on as serious adverse
      events. RESULTS: In regard to NMS, the signal scores for haloperidol and
      aripiprazole were greater than for other antipsychotics. Significant signals of
      the QT prolongation adverse event were detected only for ziprasidone and
      risperidone. With respect to leukopenia, the association with clozapine was
      noteworthy. In the case of suicide attempt, signals for haloperidol, olanzapine,
      quetiapine, risperidone, and aripiprazole were detected. CONCLUSIONS: It was
      suggested that there is a level of diversity in the strength of the association
      between various first- and second-generation antipsychotics with associated
      serious adverse events, which possibly lead to fatal outcomes. We recommend that
      research be continued in order to gather a large variety and quantity of related
      information, and that both available and newly reported data be placed in the
      context of multiple medical viewpoints in order to lead to improved levels of
      care.

PMID- 25589892
TI  - New adipose tissue formation by human adipose-derived stem cells with hyaluronic
      acid gel in immunodeficient mice.
AB  - BACKGROUND: Currently available injectable fillers have demonstrated limited
      durability. This report proposes the in vitro culture of human adipose-derived
      stem cells (hASCs) on hyaluronic acid (HA) gel for in vivo growth of de novo
      adipose tissue. METHODS: For in vitro studies, hASCs were isolated from human
      adipose tissue and were confirmed by multi-lineage differentiation and flow
      cytometry. hASCs were cultured on HA gel. The effectiveness of cell attachment
      and proliferation on HA gel was surveyed by inverted light microscopy. For in
      vivo studies, HA gel containing hASCs, hASCs without HA gel, HA gel alone were
      allocated and subcutaneously injected into the subcutaneous pocket in the back of
      nude mice (n=6) in each group. At eight weeks post-injection, the implants were
      harvested for histological examination by hematoxylin and eosin (H&E) stain, Oil
      Red O stain and immunohistochemical staining. The human-specific Alu gene was
      examined. RESULTS: hASCs were well attachment and proliferation on the HA gel. In
      vivo grafts showed well-organized new adipose tissue on the HA gel by histologic
      examination and Oil-Red O stain. Analysis of neo-adipose tissues by PCR revealed
      the presence of the Alu gene. This study demonstrated not only the successful
      culture of hASCs on HA gel, but also their full proliferation and differentiation
      into adipose tissue. CONCLUSIONS: The efficacy of injected filler could be
      permanent since the reduction of the volume of the HA gel after bioabsorption
      could be replaced by new adipose tissue generated by hASCs. This is a promising
      approach for developing long lasting soft tissue filler.

PMID- 25589893
TI  - Identification of novel compounds against an R294K substitution of influenza A
      (H7N9) virus using ensemble based drug virtual screening.
AB  - Influenza virus H7N9 foremost emerged in China in 2013 and killed hundreds of
      people in Asia since they possessed all mutations that enable them to resist to
      all existing influenza drugs, resulting in high mortality to human. In the effort
      to identify novel inhibitors combat resistant strains of influenza virus H7N9; we
      performed virtual screening targeting the Neuraminidase (NA) protein against
      natural compounds of traditional Chinese medicine database (TCM) and ZINC natural
      products. Compounds expressed high binding affinity to the target protein was
      then evaluated for molecular properties to determine drug-like molecules. 4
      compounds showed their binding energy less than -11 Kcal/mol were selected for
      molecular dynamics (MD) simulation to capture intermolecular interactions of
      ligand-protein complexes. The molecular mechanics/Poisson-Boltzmann surface area
      (MM/PBSA) method was utilized to estimate binding free energy of the complex. In
      term of stability, NA-7181 (IUPAC namely {9-Hydroxy-10-[3-(trifluoromrthyl)
      cyclohexyl]-4.8-diazatricyclo [6.4.0.02,6]dodec-4-yl}(perhydro-1H-inden-5
      yl)formaldehyde) achieved stable conformation after 20 ns and 27 ns for ligand
      and protein root mean square deviation, respectively. In term of binding free
      energy, 7181 gave the negative value of -30.031 (KJ/mol) indicating the compound
      obtained a favourable state in the active site of the protein.

PMID- 25589894
TI  - High producing tumor necrosis factor alpha gene alleles in protection against
      severe manifestations of dengue.
AB  - Dengue virus (DENV) infection usually presents with mild self-limiting dengue
      fever (DF). Few however, would present with the more severe form of the disease,
      dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). In the present
      study, the association between IL-12B, IL-10 and TNF-alpha gene polymorphisms and
      dengue severity was investigated. METHODS: A case-control study was performed on
      a total of 120 unrelated controls, 86 DF patients and 196 DHF/DSS patients. The
      polymorphisms in IL-12B, IL-10 and TNF-alpha genes were genotyped using PCR-RFLP
      and PCR-sequencing methods. RESULTS: A protective association of TNF-alpha -308A
      allele and -308GA genotype against DHF/DSS was observed, while TNF-alpha -238A
      allele and -238GA genotype were associated with DHF/DSS. A combination of TNF
      alpha -308GA+AA genotype and IL-10 non-GCC haplotypes, IL-12B pro homozygotes
      (pro1/pro1, pro2/pro2) and IL-12B 3'UTR AC were significantly correlated with
      protective effects against DHF/DSS. An association between the cytokine gene
      polymorphisms and protection against the clinical features of severe dengue
      including thrombocytopenia and increased liver enzymes was observed in this
      study. CONCLUSION: The overall findings of the study support the correlation of
      high-producer TNF-alpha genotypes combined with low-producer IL-10 haplotypes and
      IL-12B genotypes in reduced risk of DHF/DSS.

PMID- 25589896
TI  - Predictors of spiritual care provision for patients with dementia at the end of
      life as perceived by physicians: a prospective study.
AB  - BACKGROUND: Spiritual caregiving is part of palliative care and may contribute to
      well being at the end of life. However, it is a neglected area in the care and
      treatment of patients with dementia. We aimed to examine predictors of the
      provision of spiritual end-of-life care in dementia as perceived by physicians
      coordinating the care. METHODS: We used data of the Dutch End of Life in Dementia
      study (DEOLD; 2007-2011), in which data were collected prospectively in 28 Dutch
      long-term care facilities. We enrolled newly admitted residents with dementia who
      died during the course of data collection, their families, and physicians. The
      outcome of Generalized Estimating Equations (GEE) regression analyses was whether
      spiritual care was provided shortly before death as perceived by the on-staff
      elderly care physician who was responsible for end-of-life care (last sacraments
      or rites or other spiritual care provided by a spiritual counselor or staff).
      Potential predictors were indicators of high-quality, person-centered, and
      palliative care, demographics, and some other factors supported by the
      literature. Resident-level potential predictors such as satisfaction with the
      physician's communication were measured 8 weeks after admission (baseline, by
      families and physicians), physician-level factors such as the physician's
      religious background midway through the study, and facility-level factors such as
      a palliative care unit applied throughout data collection. RESULTS: According to
      the physicians, spiritual end-of-life care was provided shortly before death to
      20.8% (43/207) of the residents. Independent predictors of spiritual end-of-life
      care were: families' satisfaction with physicians' communication at baseline (OR
      1.6, CI 1.0; 2.5 per point on 0-3 scale), and faith or spirituality very
      important to resident whether (OR 19, CI 5.6; 63) or not (OR 15, CI 5.1; 47) of
      importance to the physician. Further, female family caregiving was an independent
      predictor (OR 2.7, CI 1.1; 6.6). CONCLUSIONS: Palliative care indicators were not
      predictive of spiritual end-of-life care; palliative care in dementia may need
      better defining and implementation in practice. Physician-family communication
      upon admission may be important to optimize spiritual caregiving at the end of
      life.

PMID- 25589897
TI  - Gastric cancer review.
AB  - Gastric cancer is an aggressive disease that continues to have a daunting impact
      on global health. Despite an overall decline in incidence over the last several
      decades, gastric cancer remains the fourth most common type of cancer and is the
      second leading cause of cancer-related death worldwide. This review aims to
      discuss the global distribution of the disease and the trend of decreasing
      incidence of disease, delineate the different pathologic subtypes and their
      immunohistochemical (IHC) staining patterns and molecular signatures and
      mutations, explore the role of the pathogen H. pylori in tumorgenesis, discuss
      the increasing incidence of the disease in the young, western populations and
      define the role of biologic agents in the treatment of the disease. 

PMID- 25589895
TI  - Nanoparticle-based targeted therapeutics in head-and-neck cancer.
AB  - Head-and-neck cancer is a major form of the disease worldwide. Treatment consists
      of surgery, radiation therapy and chemotherapy, but these have not resulted in
      improved survival rates over the past few decades. Versatile nanoparticles, with
      selective tumor targeting, are considered to have the potential to improve these
      poor outcomes. Application of nanoparticle-based targeted therapeutics has
      extended into many areas, including gene silencing, chemotherapeutic drug
      delivery, radiosensitization, photothermal therapy, and has shown much promise.
      In this review, we discuss recent advances in the field of nanoparticle-mediated
      targeted therapeutics for head-and-neck cancer, with an emphasis on the
      description of targeting points, including future perspectives. 

PMID- 25589898
TI  - 28 days of creatine nitrate supplementation is apparently safe in healthy
      individuals.
AB  - BACKGROUND: Creatine monohydrate has become a very popular nutritional supplement
      for its ergogenic effects. The safety of creatine monohydrate has previously been
      confirmed. However with each novel form of creatine that emerges, its safety must
      be verified. Therefore, the purpose of this study was to examine the safety of a
      novel form of creatine, creatine nitrate (CN), over a 28 day period. METHODS: 58
      young males and females (Pooled: 24.3 +/- 3.9 years, 144.9 +/- 8.0 cm, 74.2 +/-
      13.0 kg) participated in this study across two laboratories. Subjects were
      equally and randomly assigned to consume either 1 g (n = 18) or 2 g (n = 20) of
      CN or remained unsupplemented (n = 20). Blood draws for full safety panels were
      conducted by a trained phlebotomist prior to and at the conclusion of the
      supplementation period. RESULTS: Pooled data from both laboratories revealed
      significant group x time interactions for absolute lymphocytes and absolute
      monocytes (p < 0.05). Analysis of the 1 g treatment revealed lab x time
      differences for red blood cell distribution width, platelets, absolute monocytes,
      creatinine, blood urea nitrogen (BUN):creatinine, sodium, protein, and alanine
      aminotransferase (ALT) (p < 0.05). Analysis of the 2 g treatment revealed lab x
      time differences for BUN:creatinine and ALT (p < 0.05). BUN and BUN:creatinine
      increased beyond the clinical reference range for the 2 g treatment of Lab 2, but
      BUN did not reach statistical significance. CONCLUSION: Overall, CN appears to be
      safe in both 1 g and 2 g servings daily for up to a 28 day period. While those
      with previously elevated BUN levels may see additional increases resulting in
      post-supplementation values slightly beyond normal physiological range, these
      results have minor clinical significance and are not cause for concern.
      Otherwise, all hematological safety markers remained within normal range,
      suggesting that CN supplementation has no adverse effects in daily doses up to 2
      g over 28 days and may be an alternative to creatine monohydrate supplementation.

PMID- 25589899
TI  - Antisense Modulation of RNA Processing as a Therapeutic Approach in Cancer
      Therapy.
AB  - Next-generation antisense technologies are re-emerging as viable and powerful
      approaches to the treatment of several genetic diseases. Similar strategies are
      also being applied to cancer therapy. Re-programming of the expression of
      endogenous oncogenic products to replace them with functional antagonists, by
      interfering with alternative splicing or polyadenylation, provides a promising
      novel approach to address acquired drug resistance and previously undruggable
      targets.

PMID- 25589900
TI  - Alcohol-related hospitalizations of adult motorcycle riders.
AB  - OBJECTIVE: To provide an overview of the demographic characteristics of adult
      motorcycle riders with alcohol-related hospitalizations. METHODS: Data obtained
      from the Trauma Registry System were retrospectively reviewed for trauma
      admissions at a level I trauma center between January 1, 2009 and December 31,
      2013. Out of 16,548 registered patients, detailed information was retrieved
      regarding 1,430 (8.64%) adult motorcycle riders who underwent a blood alcohol
      concentration (BAC) test. A BAC level of 50 mg/dL was defined as the cut-off
      value for alcohol intoxication. RESULTS: In this study, alcohol consumption was
      more frequently noted among male motorcycle riders, those aged 30-49 years, those
      who had arrived at the hospital in the evening or during the night, and those who
      did not wear a helmet. Alcohol consumption was associated with a lower percentage
      of sustained severe injury (injury severity score >=25) and lower frequencies of
      specific body injuries, including cerebral contusion (0.6; 95% confidence
      interval [CI] = 0.42-0.80), lung contusion (0.5; 95% CI = 0.24-0.90), lumbar
      vertebral fracture (0.1; 95% CI = 0.01-0.80), humeral fracture (0.5; 95% CI =
      0.27-0.90), and radial fracture (0.6; 95% CI = 0.40-0.89). In addition, alcohol
      intoxicated motorcycle riders who wore helmets had significantly lower
      frequencies of cranial fracture (0.4; 95% CI = 0.29-0.67), epidural hematoma
      (0.5; 95% CI = 0.29-0.79), subdural hematoma (0.4; 95% CI = 0.28-0.64),
      subarachnoid hemorrhage (0.5; 95% CI = 0.32-0.72), and cerebral contusion (0.4;
      95% CI = 0.25-0.78). CONCLUSIONS: Motorcycle riders who consumed alcohol
      presented different characteristics and bodily injury patterns relative to sober
      patients, suggesting the importance of helmet use to decrease head injuries in
      alcohol-intoxicated riders.

PMID- 25589901
TI  - The first case of human autochtonous subconjunctival dirofilariosis in Poland and
      MALT lymphoma as possible consequence of this parasitosis.
AB  - The first case of human dirofilarosis in Poland was recorded in 2007. Until that
      time our country was free of Dirofilaria repens. Recent studies show that 21,4-
      60% of dogs in Warsaw region harbour microfilariae, therefore it is becoming a
      growing problem in Central Europe. In April 2013 a subconjunctival D. repens was
      removed from the eye of 61-year-old woman. It was the twenty first case of this
      disease in Poland, the third case of eye dirofilaria and the fourth autochtonous
      case. The patient had never been abroad, so it was the first case of autochtonous
      human ocular dirofilariosis in Poland. Nine months after the D. repens had been
      removed, a MALT lymphoma was discovered. In the article we discuss whether a MALT
      lymphoma of the lacrimal gland of the eye, previously affected by the parasite,
      may be the consequence of the invasion. 

PMID- 25589902
TI  - Transcript changes in Vibrio cholerae in response to salt stress.
AB  - Vibrio cholerae, which is a serious human intestinal pathogen, often resides and
      thrives in estuaries but requires major self-regulation to overcome intestinal
      hyperosmotic stress or high salt stress in water and food. In the present study,
      we selected multiple O1 and O139 group V. cholerae strains that were isolated
      from different regions and during different years to study their salt tolerance.
      Based on the mechanisms that other bacteria use to respond to high salt stress,
      we selected salt stress-response related genes to study the mechanisms which V.
      cholerae responds to high salt stress. V. cholerae strains showed salt-resistance
      characteristics that varied in salt concentrations from 4% to 6%. However, group
      O1 and group O139 showed no significant difference in the degree of salt
      tolerance. The primary responses of bacteria to salt stress, including Na(+)
      exclusion, K(+) uptake and glutamate biosynthesis, were observed in V. cholerae
      strains. In addition, some sigma factors were up-regulated in V. cholerae
      strains, suggesting that V. cholerae may recruit common sigma factors to achieve
      an active salt stress response. However, some changes in gene transcript levels
      in response to salt stress in V. cholerae were strain-specific. In particular,
      hierarchical clustering of differentially expressed genes indicated that
      transcript levels of these genes were correlated with the degree of salt
      tolerance. Therefore, elevated transcript levels of some genes, including sigma
      factors and genes involved in peptidoglycan biosynthesis, may be due to the salt
      tolerance of strains. In addition, high salt-tolerant strains may recruit common
      as well as additional sigma factors to activate the salt stress response. 

PMID- 25589903
TI  - How could health information exchange better meet the needs of care
      practitioners?
AB  - BACKGROUND: Health information exchange (HIE) has the potential to improve the
      quality of healthcare by enabling providers with better access to patient
      information from multiple sources at the point of care. However, HIE efforts have
      historically been difficult to establish in the US and the failure rates of
      organizations created to foster HIE have been high. OBJECTIVES: We sought to
      better understand how RHIO-based HIE systems were used in practice and the
      challenges care practitioners face using them. The objective of our study were to
      so investigate how HIE can better meet the needs of care practitioners. METHODS:
      We performed a multiple-case study using qualitative methods in three communities
      in New York State. We conducted interviews onsite and by telephone with HIE users
      and non-users and observed the workflows of healthcare professionals at multiple
      healthcare organizations participating in a local HIE effort in New York State.
      RESULTS: The empirical data analysis suggests that challenges still remain in
      increasing provider usage, optimizing HIE implementations and connecting HIE
      systems across geographic regions. Important determinants of system usage and
      perceived value includes users experienced level of available information and the
      fit of use for physician workflows. CONCLUSIONS: Challenges still remain in
      increasing provider adoption, optimizing HIE implementations, and demonstrating
      value. The inability to find information reduced usage of HIE. Healthcare
      organizations, HIE facilitating organizations, and states can help support HIE
      adoption by ensuring patient information is accessible to providers through
      increasing patient consents, fostering broader participation, and by ensuring
      systems are usable.

PMID- 25589904
TI  - The implementation of an integrated information system for substance use
      screening in general medical settings.
AB  - The Massachusetts Screening, Brief Intervention and Referral to Treatment
      (MASBIRT) Program, a substance use screening program in general medical settings,
      created a web-based, point-of-care (POC), application--the MASBIRT Portal (the
      "Portal") to meet program goals. OBJECTIVES: We report on development and
      implementation of the Portal. METHODS: Five year program process outcomes
      recorded by an independent evaluator and an anonymous survey of Health Educator's
      (HEs) adoption, perceptions and Portal use with a modified version of the
      Technology Readiness Index are described. [8] Specific management team members,
      selected based on their roles in program leadership, development and
      implementation of the Portal and supervision of HEs, participated in semi
      structured, qualitative interviews. RESULTS: At the conclusion of the program 73%
      (24/33) of the HEs completed a survey on their experience using the Portal. HEs
      reported that the Portal made recording screening information easy (96%);
      improved planning their workday (83%); facilitated POC data collection (84%);
      decreased time dedicated to data entry (100%); and improved job satisfaction
      (59%). The top two barriers to use were "no or limited wireless connectivity"
      (46%) and "the tablet was too heavy/bulky to carry" (29%). Qualitative management
      team interviews identified strategies for successful HIT implementation:
      importance of engaging HEs in outlining specifications and workflow needs,
      collaborative testing prior to implementation and clear agreement on data
      collection purpose, quality requirements and staff roles. DISCUSSION: Overall,
      HEs perceived the Portal favorably with regard to time saving ability and
      improved workflow. Lessons learned included identifying core requirements early
      during system development and need for managers to institute and enforce
      consistent behavioral work norms. CONCLUSION: Barriers and HEs' views of
      technology impacted the utilization of the MASBIRT Portal. Further research is
      needed to determine best approaches for HIT system implementation in general
      medical settings.

PMID- 25589905
TI  - A survey of nursing home physicians to determine laboratory monitoring adverse
      drug event alert preferences.
AB  - OBJECTIVE: We conducted a survey of nursing home physicians to learn about (1)
      the laboratory value thresholds that clinical event monitors should use to
      generate alerts about potential adverse drug events (ADEs); (2) the specific
      information to be included in the alerts; and (3) the communication modality that
      should be used for communicating them. METHODS: Nursing home physician attendees
      of the 2010 Conference of AMDA: The Society for Post-Acute and Long-Term Care
      Medicine. RESULTS: A total of 800 surveys were distributed; 565 completed surveys
      were returned and seven surveys were excluded due to inability to verify that the
      respondents were physicians (a 70% net valid response rate). Alerting threshold
      preferences were identified for eight laboratory tests. For example, the majority
      of respondents selected thresholds of >=5.5 mEq/L for hyperkalemia (63%) and
      <=3.5 without symptoms for hypokalemia (54%). The majority of surveyed physicians
      thought alerts should include the complete active medication list, current vital
      signs, previous value of the triggering lab, medication change in the past 30
      days, and medication allergies. Most surveyed physicians felt the best way to
      communicate an ADE alert was by direct phone/voice communication (64%), followed
      by email to a mobile device (59%). CONCLUSIONS: This survey of nursing home
      physicians suggests that the majority prefer alerting thresholds that would
      generally lead to fewer alerts than if widely accepted standardized laboratory
      ranges were used. It also suggests a subset of information items to include in
      alerts, and the physicians' preferred communication modalities. This information
      might improve the acceptance of clinical event monitoring systems to detect ADEs
      in the nursing home setting.

PMID- 25589906
TI  - From bed to bench: bridging from informatics practice to theory: an exploratory
      analysis.
AB  - BACKGROUND: In 2009, Applied Clinical Informatics (ACI)--focused on applications
      in clinical informatics--was launched as a companion journal to Methods of
      Information in Medicine (MIM). Both journals are official journals of the
      International Medical Informatics Association. OBJECTIVES: To explore which
      congruencies and interdependencies exist in publications from theory to practice
      and from practice to theory and to determine existing gaps. Major topics
      discussed in ACI and MIM were analyzed. We explored if the intention of
      publishing companion journals to provide an information bridge from informatics
      theory to informatics practice and vice versa could be supported by this model.
      In this manuscript we will report on congruencies and interdependences from
      practice to theory and on major topics in MIM. METHODS: Retrospective, prolective
      observational study on recent publications of ACI and MIM. All publications of
      the years 2012 and 2013 were indexed and analyzed. RESULTS: Hundred and ninety
      six publications were analyzed (ACI 87, MIM 109). In MIM publications, modelling
      aspects as well as methodological and evaluation approaches for the analysis of
      data, information, and knowledge in biomedicine and health care were frequently
      raised - and often discussed from an interdisciplinary point of view. Important
      themes were ambient-assisted living, anatomic spatial relations, biomedical
      informatics as scientific discipline, boosting, coding, computerized physician
      order entry, data analysis, grid and cloud computing, health care systems and
      services, health-enabling technologies, health information search, health
      information systems, imaging, knowledge-based decision support, patient records,
      signal analysis, and web science. Congruencies between journals could be found in
      themes, but with a different focus on content. Interdependencies from practice to
      theory, found in these publications, were only limited. CONCLUSIONS: Bridging
      from informatics theory to practice and vice versa remains a major component of
      successful research and practice as well as a major challenge.

PMID- 25589907
TI  - The process of installing REDCap, a web based database supporting biomedical
      research: the first year.
AB  - BACKGROUND: Clinical and research data are essential for patient care, research
      and healthcare system planning. REDCapTM is a web-based tool for research data
      curatorship developed at Vanderbilt University in Nashville, USA. The Faculty of
      Health Sciences at the University of the Witwatersrand, Johannesburg South Africa
      identified the need for a cost effective data management instrument. REDCap was
      installed as per the user agreement with Vanderbilt University in August 2012.
      OBJECTIVES: In order to assist other institutions that may lack the in-house
      Information Technology capacity, this paper describes the installation and
      support of REDCap and incorporates an analysis of user uptake over the first year
      of use. METHODS: We reviewed the staffing requirements, costs of installation,
      process of installation and necessary infrastructure and end-user requests
      following the introduction of REDCap at Wits. The University Legal Office and
      Human Research Ethics Committee were consulted regarding the REDCap end-user
      agreement. Bi-monthly user meetings resulted in a training workshop in August
      2013. We compared our REDCap software user numbers and records before and after
      the first training workshop. RESULTS: Human resources were recruited from
      existing staff. Installation costs were limited to servers and security
      certificates. The total costs to provide a functional REDCap platform was less
      than $9000. Eighty-one (81) users were registered in the first year. After the
      first training workshop the user numbers increased by 59 in one month and the
      total number of active users to 140 by the end of August 2013. Custom software
      applications for REDCap were created by collaboration between clinicians and
      software developers. CONCLUSION: REDCap was installed and maintained at limited
      cost. A small number of people with defined skills can support multiple REDCap
      users in two to four hours a week. End user training increased in the number of
      users, number of projects created and the number of projects moved to production.

PMID- 25589908
TI  - Increasing patient engagement: patients' responses to viewing problem lists
      online.
AB  - OBJECTIVE: To characterize the opinions, emotions, and actions taken by patients
      who viewed their electronic problem list via an online personal health record
      (PHR). MATERIALS AND METHODS: An online survey of patients who viewed their
      problem lists, as maintained by their healthcare provider, in a web-based PHR
      linked to an electronic health record for the first time. RESULTS: A total 3,649
      patients completed the survey, yielding a response rate of 42.1%. Patient
      attitudes towards the problem list function were positive overall, with 90.4%
      rating it at least somewhat useful and 86.7% reporting they would probably or
      definitely use it again. Nearly half (45.6%) of patients identified at least one
      major or minor problem missing from their list. After viewing the list, 56.1% of
      patients reported taking at least one action in response, with 32.4% of patients
      reporting that they researched a condition on the Internet, 18.3% reported that
      they contacted their healthcare provider and 16.7% reported changing or planning
      to change a health behavior (patients could report multiple actions). 64.7% of
      patients reported feeling at least somewhat happy while viewing their problem
      list, though others reported feeling sad (30.4%), worried (35.7%) or scared
      (23.8%) (patients could report multiple emotions). A smaller number of patients
      reported feeling angry (16.6%) or ashamed (14.3%). Patients who experienced an
      emotional response were more likely to take action. CONCLUSION: Overall, patients
      found the ability to view their problem lists very useful and took action in
      response to the information. However, some had negative emotions. More research
      is needed into optimal strategies for supporting patients receiving this
      information.

PMID- 25589910
TI  - User-centered design and usability testing of an innovative health-related
      quality of life module.
AB  - OBJECTIVES: Various computerized health risk appraisals (HRAs) are available, but
      few of them assess health-related quality of life (HRQoL) in a goal-directed
      framework. This study describes the user-centered development and usability
      testing of an innovative HRQoL module that extends a validated HRA tool in
      primary care settings. METHODS: Systematic user-centered design, usability
      testing, and qualitative methods were used to develop the HRQoL module in primary
      care practices. Twenty two patients and 5 clinicians participated in two rounds
      of interactive technology think-out-loud sessions (TOLs) and semi-structured
      interviews (SSIs) to iteratively develop a four-step, computerized process that
      collects information on patient goals for meaningful life activities and current
      level of disability and presents a personalized and prioritized list of
      preventive recommendations linked to online resources. RESULTS: Analysis of TOLs
      and SSIs generated 5 categories and 11 sub-categories related to facilitators and
      barriers to usability and human-technology interaction. The categories included:
      Understanding the Purpose, Usability, Perceived Value, Literacy, and Participant
      Motivation. Some categories were inter-connected. The technology was continually
      and iteratively improved between sessions until saturation of positive feedback
      was achieved in 4 categories (addressing motivation will require more research).
      Usability of all screen units of the module was improved substantially. Clinician
      feedback emphasized the importance of the module's ability to translate the
      patient-centered HRQoL Report into actionable items for clinicians to facilitate
      shared decision-making. Complete integration of the HRQoL module into the
      existing HRA will require further development and testing. CONCLUSIONS:
      Systematic application of user-centered design and human factors principles in
      technology development and testing may significantly improve the usability and
      clinical value of health information systems. This more sophisticated approach
      helped us translate complex clinical concepts, goal-setting steps, and decision
      support processes into an accepted and value-added technology.

PMID- 25589909
TI  - Identifying consumer's needs of health information technology through an
      innovative participatory design approach among English- and Spanish-speaking
      urban older adults.
AB  - OBJECTIVES: We describe an innovative community-centered participatory design
      approach, Consumer-centered Participatory Design (C2PD), and the results of
      applying C2PD to design and develop a web-based fall prevention system. METHODS:
      We conducted focus groups and design sessions with English- and Spanish-speaking
      community-dwelling older adults. Focus group data were summarized and used to
      inform the context of the design sessions. Descriptive content analysis methods
      were used to develop categorical descriptions of design session informant's needs
      related to information technology. RESULTS: The C2PD approach enabled the
      assessment and identification of informant's needs of health information
      technology (HIT) that informed the development of a falls prevention system. We
      learned that our informants needed a system that provides variation in
      functions/content; differentiates between actionable/non-actionable
      information/structures; and contains sensory cues that support wide-ranging and
      complex tasks in a varied, simple, and clear interface to facilitate self
      management. CONCLUSIONS: The C2PD approach provides community-based
      organizations, academic researchers, and commercial entities with a systematic
      theoretically informed approach to develop HIT innovations. Our community
      centered participatory design approach focuses on consumer's technology needs
      while taking into account core public health functions.

PMID- 25589911
TI  - Design challenges for electronic medication administration record systems in
      residential aged care facilities: a formative evaluation.
AB  - INTRODUCTION: Electronic medication administration record (eMAR) systems are
      promoted as a potential intervention to enhance medication safety in residential
      aged care facilities (RACFs). The purpose of this study was to conduct an in
      practice evaluation of an eMAR being piloted in one Australian RACF before its
      roll out, and to provide recommendations for system improvements. METHODS: A
      multidisciplinary team conducted direct observations of workflow (n=34 hours) in
      the RACF site and the community pharmacy. Semi-structured interviews (n=5) with
      RACF staff and the community pharmacist were conducted to investigate their views
      of the eMAR system. Data were analysed using a grounded theory approach to
      identify challenges associated with the design of the eMAR system. RESULTS: The
      current eMAR system does not offer an end-to-end solution for medication
      management. Many steps, including prescribing by doctors and communication with
      the community pharmacist, are still performed manually using paper charts and fax
      machines. Five major challenges associated with the design of eMAR system were
      identified: limited interactivity; inadequate flexibility; problems related to
      information layout and semantics; the lack of relevant decision support; and
      system maintenance issues. We suggest recommendations to improve the design of
      the eMAR system and to optimize existing workflows. DISCUSSION: Immediate value
      can be achieved by improving the system interactivity, reducing inconsistencies
      in data entry design and offering dedicated organisational support to minimise
      connectivity issues. Longer-term benefits can be achieved by adding decision
      support features and establishing system interoperability requirements with
      stakeholder groups (e.g. community pharmacies) prior to system roll out. In
      practice evaluations of technologies like eMAR system have great value in
      identifying design weaknesses which inhibit optimal system use.

PMID- 25589912
TI  - Assessment of readiness for clinical decision support to aid laboratory
      monitoring of immunosuppressive care at U.S. liver transplant centers.
AB  - BACKGROUND: Following liver transplantation, patients require lifelong
      immunosuppressive care and monitoring. Computerized clinical decision support
      (CDS) has been shown to improve post-transplant immunosuppressive care processes
      and outcomes. The readiness of transplant information systems to implement
      computerized CDS to support post-transplant care is unknown. OBJECTIVES: a)
      Describe the current clinical information system functionality and manual and
      automated processes for laboratory monitoring of immunosuppressive care, b)
      describe the use of guidelines that may be used to produce computable logic and
      the use of computerized alerts to support guideline adherence, and c) explore
      barriers to implementation of CDS in U.S. liver transplant centers. METHODS: We
      developed a web-based survey using cognitive interviewing techniques. We surveyed
      119 U.S. transplant programs that performed at least five liver transplantations
      per year during 2010-2012. Responses were summarized using descriptive analyses;
      barriers were identified using qualitative methods. RESULTS: Respondents from 80
      programs (67% response rate) completed the survey. While 98% of programs reported
      having an electronic health record (EHR), all programs used paper-based manual
      processes to receive or track immunosuppressive laboratory results. Most programs
      (85%) reported that 30% or more of their patients used external laboratories for
      routine testing. Few programs (19%) received most external laboratory results as
      discrete data via electronic interfaces while most (80%) manually entered
      laboratory results into the EHR; less than half (42%) could integrate internal
      and external laboratory results. Nearly all programs had guidelines regarding pre
      specified target ranges (92%) or testing schedules (97%) for managing
      immunosuppressive care. Few programs used computerized alerting to notify
      transplant coordinators of out-of-range (27%) or overdue laboratory results
      (20%). CONCLUSIONS: Use of EHRs is common, yet all liver transplant programs were
      largely dependent on manual paper-based processes to monitor immunosuppression
      for post-liver transplant patients. Similar immunosuppression guidelines provide
      opportunities for sharing CDS once integrated laboratory data are available.

PMID- 25589913
TI  - Case report: patient portal versus telephone recruitment for a surgical research
      study.
AB  - BACKGROUND: Patient portal adoption has rapidly increased over the last decade.
      Most patient portal research has been done in primary care or medical
      specialties, and few studies have examined their use in surgical patients or for
      recruiting research subjects. No known studies have compared portal messaging
      with other approaches of recruitment. OBJECTIVES: This case report describes our
      experience with patient portal versus telephone recruitment for a study involving
      long-term follow up of surgical patients. METHODS: Participants were recruited
      for a study of recurrence after ventral hernia repair through telephone calls and
      patient portal messaging based on registration status with the portal. Potential
      subjects who did not have a portal account or whose portal messages were returned
      after 5 days were called. The proportion of participants enrolled with each
      method was determined and demographics of eligible patients, portal users, and
      participants were compared. RESULTS: 1359 patients were eligible for the hernia
      study, and enrollment was 35% (n=465). Most participants were recruited by
      telephone (84%, n=391); 16% (n=74) were recruited through portal messaging. Forty
      four percent of eligible participants had a registered portal account, and 14% of
      users responded to the recruitment message. Portal users were younger than non
      users (55 vs. 58 years, p<0.001); participants recruited through the portal
      versus telephone were also younger (54 vs. 59 years, p=0.001). Differences in the
      sex and racial distributions between users and non-users and between portal and
      telephone recruits were not significant. CONCLUSIONS: Portal versus telephone
      recruitment for a surgical research study demonstrated modest portal recruitment
      rates and similar demographics between recruitment methods. Published studies of
      portal-only recruitment in primary care or medical-specialty patient populations
      have demonstrated higher enrollment rates, but this case study demonstrates that
      portal recruitment for research studies in the surgical population is feasible,
      and it offers convenience to patients and researchers.

PMID- 25589915
TI  - Class II but Not Second Class-Prospects for the Development of Class II PI3K
      Inhibitors.
AB  - The Class II PI3 kinases are emerging from the shadows of their Class I cousins.
      The data emerging from PIK3C2 genetic modification studies and from siRNA
      knockdown suggest important roles in physiology and pathology. With some well
      studied Class I isoform inhibitors showing strong Class II activity and a wealth
      of crystallographic information available, the structural similarity of these
      isoforms to Class I provides both the opportunity and the challenge in design of
      selective pharmacological inhibitors. 

PMID- 25589916
TI  - Combination of novel imidazopyridazine mps-1 kinase inhibitors and bcl-2 family
      protein inhibitors.

PMID- 25589914
TI  - User centered clinical decision support tools: adoption across clinician training
      level.
AB  - BACKGROUND: Dissemination and adoption of clinical decision support (CDS) tools
      is a major initiative of the Affordable Care Act's Meaningful Use program.
      Adoption of CDS tools is multipronged with personal, organizational, and clinical
      settings factoring into the successful utilization rates. Specifically, the
      diffusion of innovation theory implies that 'early adopters' are more inclined to
      use CDS tools and younger physicians tend to be ranked in this category.
      OBJECTIVE: This study examined the differences in adoption of CDS tools across
      providers' training level. PARTICIPANTS: From November 2010 to 2011, 168
      residents and attendings from an academic medical institution were enrolled into
      a randomized controlled trial. INTERVENTION: The intervention arm had access to
      the CDS tool through the electronic health record (EHR) system during strep and
      pneumonia patient visits. MAIN MEASURES: The EHR system recorded details on how
      intervention arm interacted with the CDS tool including acceptance of the initial
      CDS alert, completion of risk-score calculators and the signing of medication
      order sets. Using the EHR data, the study performed bivariate tests and general
      estimating equation (GEE) modeling to examine the differences in adoption of the
      CDS tool across residents and attendings. KEY RESULTS: The completion rates of
      the CDS calculator and medication order sets were higher amongst first year
      residents compared to all other training levels. Attendings were the less likely
      to accept the initial step of the CDS tool (29.3%) or complete the medication
      order sets (22.4%) that guided their prescription decisions, resulting in
      attendings ordering more antibiotics (37.1%) during an CDS encounter compared to
      residents. CONCLUSION: There is variation in adoption of CDS tools across
      training levels. Attendings tended to accept the tool less but ordered more
      medications. CDS tools should be tailored to clinicians' training levels.

PMID- 25589917
TI  - Pyrrolopyrimidine Analogues as MKNK Inhibitors.

PMID- 25589918
TI  - Dual leucine zipper kinase inhibitors: potential treatments for neurodegenerative
      diseases.

PMID- 25589919
TI  - RET Kinase Inhibitors May Treat Cancer and Gastrointestinal Disorders.

PMID- 25589920
TI  - Quinalozinones as Inhibitors of Class I PI3K Kinases.

PMID- 25589921
TI  - P21-Activated Kinase 4 (PAK4) Inhibitors as Potential Cancer Therapy.

PMID- 25589922
TI  - Novel azaindazole sulfonamides inhibitors of serum and glucocorticoid regulated
      kinase.

PMID- 25589923
TI  - Pyrrolopyridines-quinazolines Inhibitors of PKR-Like ER Kinase.

PMID- 25589924
TI  - Novel Disubstituted Pyrimidines as Inhibitors of Bruton's Tyrosine Kinase.

PMID- 25589927
TI  - Structure-Based Drug Design of Novel Potent and Selective Tetrahydropyrazolo[1,5
      a]pyrazines as ATR Inhibitors.
AB  - A saturation strategy focused on improving the selectivity and physicochemical
      properties of ATR inhibitor HTS hit 1 led to a novel series of highly potent and
      selective tetrahydropyrazolo[1,5-a]pyrazines. Use of PI3Kalpha mutants as ATR
      crystal structure surrogates was instrumental in providing cocrystal structures
      to guide the medicinal chemistry designs. Detailed DMPK studies involving cyanide
      and GSH as trapping agents during microsomal incubations, in addition to
      deuterium-labeled compounds as mechanistic probes uncovered the molecular basis
      for the observed CYP3A4 TDI in the series. 

PMID- 25589925
TI  - Fragment-based discovery of type I inhibitors of maternal embryonic leucine
      zipper kinase.
AB  - Fragment-based drug design was successfully applied to maternal embryonic leucine
      zipper kinase (MELK). A low affinity (160 MUM) fragment hit was identified, which
      bound to the hinge region with an atypical binding mode, and this was optimized
      using structure-based design into a low-nanomolar and cell-penetrant inhibitor,
      with a good selectivity profile, suitable for use as a chemical probe for
      elucidation of MELK biology. 

PMID- 25589926
TI  - Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic
      Leucine Zipper Kinase.
AB  - A novel Type II kinase inhibitor chemotype has been identified for maternal
      embryonic leucine zipper kinase (MELK) using structure-based ligand design. The
      strategy involved structural characterization of an induced DFG-out pocket by
      protein-ligand X-ray crystallography and incorporation of a slender linkage
      capable of bypassing a large gate-keeper residue, thus enabling design of
      molecules accessing both hinge and induced pocket regions. Optimization of an
      initial hit led to the identification of a low-nanomolar, cell-penetrant Type II
      inhibitor suitable for use as a chemical probe for MELK. 

PMID- 25589928
TI  - Structure-Based Drug Design of Novel, Potent, and Selective Azabenzimidazoles
      (ABI) as ATR Inhibitors.
AB  - Compound 13 was discovered through morphing of the ATR biochemical HTS hit 1. The
      ABI series was potent and selective for ATR. Incorporation of a 6-azaindole
      afforded a marked increase in cellular potency but was associated with poor PK
      and hERG ion channel inhibition. DMPK experiments established that CYP P450 and
      AO metabolism in conjunction with Pgp and BCRP efflux were major causative
      mechanisms for the observed PK. The series also harbored the CYP3A4 TDI liability
      driven by the presence of both a morpholine and an indole moiety. Incorporation
      of an adjacent fluorine or nitrogen into the 6-azaindole addressed many of the
      various medicinal chemistry issues encountered. 

PMID- 25589929
TI  - Quantification of a Pharmacodynamic ERK End Point in Melanoma Cell Lysates:
      Toward Personalized Precision Medicine.
AB  - Protein kinases are mutated or otherwise rendered constitutively active in
      numerous cancers where they are attractive therapeutic targets with well over a
      dozen kinase inhibitors now being used in therapy. While fluorescent sensors have
      capacity to measure changes in kinase activity, surprisingly they have not been
      utilized for biomarker studies. A first-generation peptide sensor for ERK based
      on the Sox fluorophore is described. This sensor called ERK-sensor-D1 possesses
      high activity toward ERK and more than 10-fold discrimination over other MAPKs.
      The sensor can rapidly quantify ERK activity in cell lysates and monitor ERK
      pathway engagement by BRAF and MEK inhibitors in cultured melanoma cell lines.
      The dynamic range of the sensor assay allows ERK activities that have potential
      for profound clinical consequences to be rapidly distinguished. 

PMID- 25589930
TI  - Discovery of a Type III Inhibitor of LIM Kinase 2 That Binds in a DFG-Out
      Conformation.
AB  - The first allosteric, type III inhibitor of LIM-kinase 2 (LIMK2) is reported. A
      series of molecules that feature both an N-phenylsulfonamide and tertiary amide
      were not only very potent at LIMK2 but also were extremely selective against a
      panel of other kinases. Enzymatic kinetic studies showed these molecules to be
      noncompetitive with ATP, suggesting allosteric inhibition. X-ray crystallography
      confirmed that these sulfonamides are a rare example of a type III kinase
      inhibitor that binds away from the highly conserved hinge region and instead
      resides in the hydrophobic pocket formed in the DFG-out conformation of the
      kinase, thus accounting for the high level of selectivity observed. 

PMID- 25589931
TI  - Pyrimidine-based tricyclic molecules as potent and orally efficacious inhibitors
      of wee1 kinase.
AB  - Aided by molecular modeling, compounds with a pyrimidine-based tricyclic scaffold
      were designed and confirmed to inhibit Wee1 kinase. Structure-activity studies
      identified key pharmacophores at the aminoaryl and halo-benzene regions
      responsible for binding affinity with sub-nM K i values. The potent inhibitors
      demonstrated sub-MUM activities in both functional and mechanism-based cellular
      assays and also possessed desirable pharmacokinetic profiles. The lead molecule,
      31, showed oral efficacy in potentiating the antiproliferative activity of
      irinotecan, a cytotoxic agent, in a NCI-H1299 mouse xenograft model. 

PMID- 25589932
TI  - Synthesis and Biological Evaluation of Pyrazolo[1,5-a]pyrimidine Compounds as
      Potent and Selective Pim-1 Inhibitors.
AB  - Pim-1 has emerged as an attractive target for developing therapeutic agents for
      treating disorders involving abnormal cell growth, especially cancers. Herein we
      present lead optimization, chemical synthesis and biological evaluation of
      pyrazolo[1,5-a]pyrimidine compounds as potent and selective inhibitors of Pim-1
      starting from a hit from virtual screening. These pyrazolo[1,5-a]pyrimidine
      compounds strongly inhibited Pim-1 and Flt-3 kinases. Selected compounds
      suppressed both the phosphorylation of BAD protein in a cell-based assay and 2
      dimensional colony formation in a clonogenic cell survival assay at submicromolar
      potency, suggesting that cellular activity was mediated through inhibition of Pim
      1. Moreover, these Pim-1 inhibitors did not show significant hERG inhibition at
      30 MUM concentration. The lead compound proved to be highly selective against a
      panel of 119 oncogenic kinases, indicating it had an improved safety profile
      compared with the first generation Pim-1 inhibitor SGI-1776. 

PMID- 25589933
TI  - Unfolded Protein Response in Cancer: IRE1alpha Inhibition by Selective Kinase
      Ligands Does Not Impair Tumor Cell Viability.
AB  - The kinase/endonuclease inositol requiring enzyme 1 (IRE1alpha), one of the
      sensors of unfolded protein accumulation in the endoplasmic reticulum that
      triggers the unfolded protein response (UPR), has been investigated as an
      anticancer target. We identified potent allosteric inhibitors of IRE1alpha
      endonuclease activity that bound to the kinase site on the enzyme. Structure
      activity relationship (SAR) studies led to 16 and 18, which were selective in
      kinase screens and were potent against recombinant IRE1alpha endonuclease as well
      as cellular IRE1alpha. The first X-ray crystal structure of a kinase inhibitor
      (16) bound to hIRE1alpha was obtained. Screening of native tumor cell lines
      (>300) against selective IRE1alpha inhibitors failed to demonstrate any effect on
      cellular viability. These results suggest that IRE1alpha activity is not
      essential for viability in most tumor cell lines, in vitro, and that interfering
      with the survival functions of the UPR may not be an effective strategy to block
      tumorigenesis. 

PMID- 25589934
TI  - Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly
      Active and Selective SGK1 Inhibitors.
AB  - From a virtual screening starting point, inhibitors of the serum and
      glucocorticoid regulated kinase 1 were developed through a combination of
      classical medicinal chemistry and library approaches. This resulted in highly
      active small molecules with nanomolar activity and a good overall in vitro and
      ADME profile. Furthermore, the compounds exhibited unusually high kinase and off
      target selectivity due to their rigid structure. 

PMID- 25589935
TI  - Structural Analysis of the Binding of Type I, I1/2, and II Inhibitors to Eph
      Tyrosine Kinases.
AB  - We have solved the crystal structures of the EphA3 tyrosine kinase in complex
      with nine small-molecule inhibitors, which represent five different chemotypes
      and three main binding modes, i.e., types I and I1/2 (DFG in) and type II (DFG
      out). The three structures with type I1/2 inhibitors show that the higher
      affinity with respect to type I is due to an additional polar group (hydroxyl or
      pyrazole ring of indazole) which is fully buried and is involved in the same
      hydrogen bonds as the (urea or amide) linker of the type II inhibitors. Overall,
      the type I and type II binding modes belong to the lock-and-key and induced fit
      mechanism, respectively. In the type II binding, the scaffold in contact with the
      hinge region influences the position of the Phe765 side chain of the DFG motif
      and the orientation of the Gly-rich loop. The binding mode of Birb796 in the
      EphA3 kinase does not involve any hydrogen bond with the hinge region, which is
      different from the Birb796/p38 MAP kinase complex. Our structural analysis
      emphasizes the importance of accounting for structural plasticity of the ATP
      binding site in the design of type II inhibitors of tyrosine kinases. 

PMID- 25589936
TI  - Discovery and Development of LX7101, a Dual LIM-Kinase and ROCK Inhibitor for the
      Treatment of Glaucoma.
AB  - The structure of LX7101, a dual LIM-kinase and ROCK inhibitor for the treatment
      of ocular hypertension and associated glaucoma, is disclosed. Previously reported
      LIM kinase inhibitors suffered from poor aqueous stability due to solvolysis of
      the central urea. Replacement of the urea with a hindered amide resulted in
      aqueous stable compounds, and addition of solubilizing groups resulted in a set
      of compounds with good properties for topical dosing in the eye and good efficacy
      in a mouse model of ocular hypertension. LX7101 was selected as a clinical
      candidate from this group based on superior efficacy in lowering intraocular
      pressure and a good safety profile. LX7101 completed IND enabling studies and was
      tested in a Phase 1 clinical trial in glaucoma patients, where it showed efficacy
      in lowering intraocular pressure. 

PMID- 25589937
TI  - Distinct binding mode of multikinase inhibitor lenvatinib revealed by biochemical
      characterization.
AB  - Lenvatinib is an oral multikinase inhibitor that selectively inhibits vascular
      endothelial growth factor (VEGF) receptors 1 to 3 and other proangiogenic and
      oncogenic pathway-related receptor tyrosine kinases. To elucidate the origin of
      the potency of lenvatinib in VEGF receptor 2 (VEGFR2) inhibition, we conducted a
      kinetic interaction analysis of lenvatinib with VEGFR2 and X-ray analysis of the
      crystal structure of VEGFR2-lenvatinib complexes. Kinetic analysis revealed that
      lenvatinib had a rapid association rate constant and a relatively slow
      dissociation rate constant in complex with VEGFR2. Co-crystal structure analysis
      demonstrated that lenvatinib binds at its ATP mimetic quinoline moiety to the ATP
      binding site and to the neighboring region via a cyclopropane ring, adopting an
      Asp-Phe-Gly (DFG)-"in" conformation. These results suggest that lenvatinib is
      very distinct in its binding mode of interaction compared to the several approved
      VEGFR2 kinase inhibitors. 

PMID- 25589939
TI  - New Frontiers in Kinases: Second Generation Inhibitors-Going beyond Cancer.

PMID- 25589938
TI  - Synthesis and Structure-Activity Relationship Study of 5a-Carbasugar Analogues of
      SL0101.
AB  - The Ser/Thr protein kinase, RSK, is associated with oncogenesis, and therefore,
      there are ongoing efforts to develop RSK inhibitors that are suitable for use in
      vivo. SL0101 is a natural product that demonstrates selectivity for RSK
      inhibition. However, SL0101 has a short biological half-life in vivo. To address
      this issue we designed a set of eight cyclitol analogues, which should be
      resistant to acid catalyzed anomeric bond hydrolysis. The analogues were
      synthesized and evaluated for their ability to selectively inhibit RSK in vitro
      and in cell-based assays. All the analogues were prepared using a stereodivergent
      palladium-catalyzed glycosylation/cyclitolization for installing the aglycon. The
      l-cyclitol analogues were found to inhibit RSK2 in in vitro kinase activity with
      a similar efficacy to that of SL0101, however, the analogues were not specific
      for RSK in cell-based assays. In contrast, the d-isomers showed no RSK inhibitory
      activity in in vitro kinase assay. 

PMID- 25589940
TI  - Complex regional pain syndrome: time to study the supraspinal role?

PMID- 25589941
TI  - Etifoxine for pain patients with anxiety.
AB  - Etifoxine (etafenoxine, Stresam(r)) is a non-benzodiazepine anxiolytic with an
      anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is
      currently being studied for its ability to promote peripheral nerve healing and
      to treat chemotherapy-induced pain. In addition to being mediated by GABAAalpha2
      receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects
      directly by binding to beta2 or beta3 subunits of the GABAA receptor complex. It
      also modulates GABAA receptors indirectly via stimulation of neurosteroid
      production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the
      outer mitochondrial membrane in the central and peripheral nervous systems,
      previously known as the peripheral benzodiazepine receptor (PBR). Therefore, the
      effects of etifoxine are not completely reversed by the benzodiazepine antagonist
      flumazenil. Etifoxine is used for various emotional and bodily reactions followed
      by anxiety. It is contraindicated in situations such as shock, severely impaired
      liver or kidney function, and severe respiratory failure. The average dosage is
      150 mg per day for no more than 12 weeks. The most common adverse effect is
      drowsiness at the initial stage. It does not usually cause any withdrawal
      syndromes. In conclusion, etifoxine shows less adverse effects of anterograde
      amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes
      than those of benzodiazepines. It potentiates GABAA receptor-function by a direct
      allosteric effect and by an indirect mechanism involving the activation of TSPO.
      It seems promising that non-benzodiazepine anxiolytics including etifoxine will
      replenish shortcomings of benzodiazepines and selective serotonin reuptake
      inhibitors according to animated studies related to TSPO. 

PMID- 25589942
TI  - Comparison of the efficacy of caudal, interlaminar, and transforaminal epidural
      injections in managing lumbar disc herniation: is one method superior to the
      other?
AB  - BACKGROUND: Epidural injections are performed utilizing 3 approaches in the
      lumbar spine: caudal, interlaminar, and transforaminal. The literature on the
      efficacy of epidural injections has been sporadic. There are few high-quality
      randomized trials performed under fluoroscopy in managing disc herniation that
      have a long-term follow-up and appropriate outcome parameters. There is also a
      lack of literature comparing the efficacy of these 3 approaches. METHODS: This
      manuscript analyzes data from 3 randomized controlled trials that assessed a
      total of 360 patients with lumbar disc herniation. There were 120 patients per
      trial either receiving local anesthetic alone (60 patients) or local anesthetic
      with steroids (60 patients). RESULTS: Analysis showed similar efficacy for
      caudal, interlaminar, and transforaminal approaches in managing chronic pain and
      disability from disc herniation. The analysis of caudal epidural injections
      showed the potential superiority of steroids compared with local anesthetic alone
      a 2-year follow-up, based on the average relief per procedure. In the
      interlaminar group, results were somewhat superior for pain relief in the steroid
      group at 6 months and functional status at 12 months. Interlaminar epidurals
      provided improvement in a significantly higher proportion of patients. The
      proportion of patients nonresponsive to initial injections was also lower in the
      group for local anesthetic with steroid in the interlaminar trial. CONCLUSIONS:
      The results of this assessment show significant improvement in patients suffering
      from chronic lumbar disc herniation with 3 lumbar epidural approaches with local
      anesthetic alone, or using steroids with long-term follow-up of up to 2 years, in
      a contemporary interventional pain management setting.

PMID- 25589943
TI  - Comparative Study of the Effects of the Retrocrural Celiac Plexus Block Versus
      Splanchnic Nerve Block, C-arm Guided, for Upper Gastrointestinal Tract Tumors on
      Pain Relief and the Quality of Life at a Six-month Follow Up.
AB  - BACKGROUND: The celiac plexus and splanchnic nerves are targets for neurolytic
      blocks for pain relief from pain caused by upper gastrointestinal tumors.
      Therefore, we investigated the analgesic effect of a celiac plexus block versus a
      splanchnic nerve block and the effects of these blocks on the quality of life six
      months post-intervention for patients with upper GIT tumors. METHODS: Seventy
      nine patients with inoperable upper GIT tumors and with severe uncontrolled
      visceral pain were randomized into two groups. These were Group I, for whom a
      celiac plexus block was used with a bilateral needle retrocrural technique, and
      Group II, for whom a splanchnic nerve block with a bilateral needle technique was
      used. The visual analogue scale for pain (0 to 100), the quality of life via the
      QLQ-C30 questionnaire, and survival rates were assessed. RESULTS: Pain scores
      were comparable in both groups in the first week after the block. Significantly
      more patients retained good analgesia with tramadol in the splanchnic group from
      16 weeks onwards (P = 0.005, 0.001, 0.005, 0.001, 0.01). Social and cognitive
      scales improved significantly from the second week onwards in the splanchnic
      group. Survival of both groups was comparable. CONCLUSIONS: The results of this
      study demonstrate that the efficacy of the splanchnic nerve block technique
      appears to be clinically comparable to a celiac block. All statistically
      significant differences are of little clinical value.

PMID- 25589944
TI  - A Pilot Study of the Correlation between the Numeric Rating Scale used to
      Evaluate "Geop" and Questionnaires on Pain Perception.
AB  - BACKGROUND: The word "geop" is a unique Korean term commonly used to describe
      fright, fear and anxiety, and similar concepts. The purpose of this pilot study
      is to examine the correlation between the Numeric Rating Scale (NRS) score of
      geop and three different questionnaires on pain perception. METHODS: Patients
      aged 20 to 70 years who visited our outpatient pain clinics were evaluated. They
      were requested to rate the NRS score (range: 0-100) if they felt geop. Next, they
      completed questionnaires on pain perception, in this case the Korean version of
      the Pain Sensitivity Questionnaire (PSQ), the Pain Catastrophizing Scale (PCS),
      and the Pain Anxiety Symptoms Scale (PASS). The correlations among each variable
      were evaluated by statistical analyses. RESULTS: There was no statistically
      significant correlation between the NRS score of geop and the PSQ score (r =
      0.075, P = 0.5605). The NRS score of geop showed a significant correlation with
      the PCS total score (r = 0.346, P = 0.0063). Among the sub-scales, Rumination (r
      = 0.338, P = 0.0077) and Magnification (r = 0.343, P = 0.0069) were correlated
      with the NRS score of geop. In addition, the NRS score of geop showed a
      significant correlation with the PASS total score (r = 0.475, P = 0.0001). The
      cognitive (r = 0.473, P = 0.0002) and fear factors (r = 0.349, P = 0.0063) also
      showed significant correlations with the NRS score of geop. CONCLUSIONS: This
      study marks the first attempt to introduce the concept of "geop." The NRS score
      of geop showed a moderate positive correlation with the total PCS and PASS score.
      However, further investigations are required before the "geop" concept can be
      used practically in clinical fields.

PMID- 25589945
TI  - Comparison of ramosetron plus dexamethasone with ramosetron alone on
      postoperative nausea, vomiting, shivering and pain after thyroid surgery.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV), postanesthetic shivering
      and pain are common postoperative patient complaints that can result in adverse
      physical and psychological outcomes. Some antiemetics are reported to be
      effective in the management of postoperative pain and shivering, as well as PONV.
      We evaluated the efficacy of dexamethasone added to ramosetron on PONV, shivering
      and pain after thyroid surgery. METHODS: One hundred and eight patients scheduled
      for thyroid surgery were randomly allocated to three different groups: the
      control group (group C, n = 36), the ramosetron group (group R, n = 36), or the
      ramosetron plus dexamethasone group (group RD, n = 36). The patients were treated
      intravenously with 1 and 2 ml of 0.9% NaCl (group C); or 2 ml of 0.15 mg/ml
      ramosetron plus 1 ml of 0.9% NaCl (group R); or 2 ml of 0.15 mg/ml ramosetron
      plus 1 ml of 5 mg/ml dexamethasone (group RD) immediately after anesthesia.
      RESULTS: Incidence of nausea and the need for rescue antiemetics, verbal rating
      scale (VRS) 1 hour pain value, ketorolac consumption, and incidence of shivering
      were significantly lower in group R and group RD, than in group C (P < 0.05).
      Moreover, these parameters were significantly lower in group RD than in group R
      (P < 0.05). CONCLUSIONS: Combination of ramosetron and dexamethasone
      significantly reduced not only the incidence of nausea and need for rescue
      antiemetics, but also the VRS 1 hour pain value, ketorolac consumption, and the
      incidence of shivering compared to ramosetron alone in patients undergoing
      thyroid surgery.

PMID- 25589946
TI  - A comparison of three methods for postoperative pain control in patients
      undergoing arthroscopic shoulder surgery.
AB  - BACKGROUND: Arthroscopic shoulder operations (ASS) are often associated with
      severe postoperative pain. Nerve blocks have been studied for pain in shoulder
      surgeries. Interscalene brachial plexus blocks (ISB) and an intra-articular
      injection (IA) have been reported in many studies. The aim of the present study
      is to evaluate the effect of ISB, a continuous cervical epidural block (CCE) and
      IA as a means of postoperative pain control and to study the influence of these
      procedures on postoperative analgesic consumption and after ASS. METHODS: Fifty
      seven patients who underwent ASS under general anesthesia were randomly assigned
      to one of three groups: the ISB group (n = 19), the CCE group (n = 19), and the
      IA group (n = 19). Patients in each group were evaluated on a postoperative
      numerical rating scale (NRS), their rescue opioid dosage (ROD), and side effects.
      RESULTS: Postoperative NRSs were found to be higher in the IA group than in the
      ISB and CCE groups both at rest and on movement. The ROD were 1.6 +/- 2.3, 3.0 +/
      4.9 and 7.1 +/- 7.9 mg morphine equivalent dose in groups CCE, ISB, and IA
      groups (P = 0.001), respectively, and statistically significant differences were
      noted between the CCE and IA groups (P = 0.01) but not in between the ISB and CCE
      groups. CONCLUSIONS: This prospective, randomized study demonstrated that ISB is
      as effective analgesic technique as a CCE for postoperative pain control in
      patients undergoing ASS.

PMID- 25589947
TI  - Successful Treatment of Rectus Femoris Calcification with Ultrasound-guided
      Injection: A Case Report.
AB  - Painful periarticular calcification most commonly occurs within the rotator cuff
      of the shoulder and rarely around the elbow, hip, foot, and neck. As acute
      inflammatory reaction develops, severe pain, exquisite tenderness, local
      swelling, and limitation of motion with pain occur. In case of calcific
      tendinitis of the shoulder, it can be easily diagnosed according to the symptoms
      and with x-ray. However, in lesions of the hip, as it is a rare location and
      usually involves pain in the posterolateral aspect of the thigh, which can
      simulate radicular pain from a lumbar intervertebral disc, it could be difficult
      to diagnose. Hence, physicians usually focus on lumbar lesions; therefore,
      misdiagnosis is common and leads to a delayed management. Here, we report the
      case of a 30-year-old female patient with calcific tendinitis of the rectus
      femoris that was successfully managed with ultrasound-guided steroid injection.
      This study offers knowledge about the rectus femoris calcification. 

PMID- 25589948
TI  - Spinal cord stimulation for intractable visceral pain due to sphincter of oddi
      dysfunction.
AB  - Sphincter of Oddi dysfunction (SOD) is a syndrome of chronic biliary pain or
      recurrent pancreatitis due to the functional obstruction of the
      pancreaticobiliary flow. We report a case of spinal cord stimulation (SCS) for
      chronic abdominal pain due to SOD. The patient had a history of cholecystectomy
      and had suffered from chronic right upper quadrant abdominal pain. The patient
      had been diagnosed as having SOD. The patient was treated with opioid analgesics
      and nerve blocks, including a splanchnic nerve block. However, two years later,
      the pain became intractable. We implanted percutaneous SCS at the T5-7 level for
      this patient. Visual analog scale (VAS) scores for pain and the amount of opioid
      intake decreased. The patient was tracked for more than six months without
      significant complications. From our clinical case, SCS is an effective and
      alternative treatment option for SOD. Further studies and long-term follow-up are
      necessary to understand the effectiveness and the limitations of SCS on SOD. 

PMID- 25589949
TI  - The effect of stellate ganglion block on intractable lymphedema after breast
      cancer surgery.
AB  - Lymphedema of the upper limb after breast cancer surgery is a disease that
      carries a life-long risk and is difficult to cure once it occurs despite the
      various treatments which have been developed. Two patients were referred from
      general surgery department for intractable lymphedema. They were treated with
      stellate ganglion blocks (SGBs), and the circumferences of the mid-point of their
      each upper and lower arms were measured on every visit to the pain clinic. A
      decrease of the circumference in each patient was observed starting after the
      second injection. A series of blocks were established to maintain a prolonged
      effect. Both patients were satisfied with less swelling and pain. This case
      demonstrates the benefits of an SGB for intractable upper limb lymphedema. 

PMID- 25589950
TI  - Which methods of epidural steroid injections is more effective in reducing the
      radicular pain; transforaminal or interlaminar?

PMID- 25589951
TI  - Chronic kidney disease in the elderly: evaluation and management.
AB  - Chronic kidney disease (CKD) is a very common clinical problem in elderly
      patients and is associated with increased morbidity and mortality. As life
      expectancy continues to improve worldwide, there is a rising prevalence of
      comorbidities and risk factors such as hypertension and diabetes predisposing to
      a high burden of CKD in this population. The body of knowledge on the approach to
      elderly patient with CKD is still evolving. Thus, this review seeks to explore
      the epidemiology and to discuss current understanding of challenges in the
      diagnosis and management of elderly patients CKD.

PMID- 25589954
TI  - The next challenge for VATS lobectomy surgeons.

PMID- 25589953
TI  - MMP9-sensitive polymers mediate environmentally-responsive bivalirudin release
      and thrombin inhibition.
AB  - MMP9-responsive bivalirudin-HPMA copolymers were synthesized for direct, local
      administration in rat spinal cord contusion injury models. Polymer-conjugated
      bivalirudin peptides maintained activity while demonstrating enzyme-mediated
      release upon MMP9 exposure and prolonged release from hyaluronic
      acid/methylcellulose (HAMC) hydrogels compared to free bivalirudin peptide.
      Localized administration of bivalirudin copolymers in vivo at the site of rat
      spinal cord injury decreased cellular proliferation and astrogliosis, suggesting
      the bivalirudin copolymer and HAMC hydrogel system are a promising therapeutic
      intervention for reducing immediate inflammatory responses and long term
      scarring. 

PMID- 25589952
TI  - Situs inversus and ciliary abnormalities: 20 years later, what is the connection?
AB  - Heterotaxy (also known as situs ambiguous) and situs inversus totalis describe
      disorders of laterality in which internal organs do not display their typical
      pattern of asymmetry. First described around 1600 by Girolamo Fabrizio, numerous
      case reports about laterality disorders in humans were published without any idea
      about the underlying cause. Then, in 1976, immotile cilia were described as the
      cause of a human syndrome that was previously clinically described, both in 1904
      by AK Siewert and in 1933 by Manes Kartagener, as an association of situs
      inversus with chronic sinusitis and bronchiectasis, now commonly known as
      Kartagener's syndrome. Despite intense research, the underlying defect of
      laterality disorders remained unclear. Nearly 20 years later in 1995, Bjorn
      Afzelius discussed five hypotheses to explain the connection between ciliary
      defects and loss of laterality control in a paper published in the International
      Journal of Developmental Biology asking: 'Situs inversus and ciliary
      abnormalities: What is the connection?'. Here, nearly 20 research years later, we
      revisit some of the key findings that led to the current knowledge about the
      connection between situs inversus and ciliary abnormalities. 

PMID- 25589955
TI  - Spontaneous esophageal rupture as the underlying cause of pneumothorax: early
      recognition is crucial.
AB  - Boerhaave's syndrome (BS), also known as "spontaneous rupture of the esophagus",
      constitutes an emergency that requires early diagnosis if death or serious
      morbidity are to be prevented. First described in 1724, BS is thought to be more
      common than once thought. Its true incidence remains unknown. Mortality ranges
      between 20-40% with timely treatment but this rises to virtually 100% if
      treatment is delayed by more than 48 hours. This is unfortunately a common
      occurrence due to delayed diagnosis. The commonest precipitating factor is
      vomiting but BS can be truly "spontaneous". The classical clinical presentation
      described consists of vomiting, chest pain, and subcutaneous emphysema. However,
      and contrary to popular belief, this triad is actually uncommon accounting for
      the frequently delayed diagnosis. A less recognised presenting feature of BS is
      with pneumothorax due to associated rupture of the parietal pleura. Pneumothorax
      has been shown to be present in more than 20% of cases of BS-sometimes with a
      coexistent pleural effusion (hydropneumothorax). This article aims to raise
      awareness about pneumothorax as the sole initial presenting feature of BS and
      alert clinicians to consider BS in the differential diagnosis of any patient with
      respiratory symptoms and a recent history of vomiting. 

PMID- 25589956
TI  - Big data and clinical research: perspective from a clinician.

PMID- 25589957
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration: a maturing
      technique.

PMID- 25589958
TI  - The lung cancer epidemic in Spanish women: an analysis of mortality rates over a
      37-year period.
AB  - BACKGROUND: Lung cancer continues to be the leading cause of cancer-related
      mortality in the European Union (EU) and deaths from lung cancer have been
      projected to escalate to epidemic proportions amongst females over the next
      years. We examined lung cancer mortality rates in men and women from Andalusia
      (Spain) over a 37-year period [1975-2012]. METHODS: Longitudinal epidemiological
      study analyzing lung cancer mortality trends in males and females. Data on lung
      cancer mortality in Andalusia for the period 1975-2012 were obtained from the
      official cause-of-death publications of the Institute of Statistics of Andalusia.
      For each sex, age-standardized (European standard population) mortality rates
      (ASR) from lung cancer were calculated for all ages and truncated at 30-64, 65
      74, and >75 years using the direct method. Standardized rate trends by age and
      sex were estimated by joinpoint regression analysis. RESULTS: In men, the ASR
      steadily increased through the period 1993-1995, reaching a peak of 145.72
      deaths/100,000 people. Subsequently, lung cancer deaths decreased to a rate of
      125.47 in the 2011-2012 period. A moderate increase was seen in women until the
      late 1990s and early 2000s. Thereafter, a very notable rise was observed in
      females for all age groups, the only exception being older subjects. The sex
      differences decreased from 8.6:1 in the 1975-1977 period to 6.8:1 in the 2011
      2012 period. CONCLUSIONS: Lung cancer mortality rates decreased significantly in
      Andalusian men from 1975 to 2012. More importantly, we demonstrate for the first
      time the beginning of the lung cancer epidemics in Andalusian women as previously
      predicted for this area.

PMID- 25589959
TI  - Treatment of giant emphysamous bulla with endobronchial valves in patients with
      chronic obstructive pulmonary disease: a case series.
AB  - BACKGROUND: Giant emphysamtous bulla (GEB) can negatively affect the pulmonary
      functions of chronic obstructive pulmonary diseases (COPD) patients, including
      decreased forced expiratory volume in 1 s (FEV1) and increased functional
      residual capacity (FRC). The aim of this study was to evaluate the efficacy of
      endobronchial valve (EBV) to treat bullae and to find efficacy predictors of
      successful treatment. METHODS: Five COPD patients with giant bulla were treated
      using EBVs. Before the EBV deployment, collateral ventilation (CV) between the
      targeted and adjacent lobes was evaluated with Chartis system. RESULTS: In the
      two patients with negative CV, the mean value of FEV1 increased from 27.1+/-11.4%
      of predicted value before EBV treatment to 32.8+/-12.0% (P>0.05) at 1 month after
      EBV treatment, than to 31.7+/-24.5% (P>0.05) at 6 months after EBV treatment.
      Only one patient, whose bulla occupied the whole right middle lung, displayed
      sustained improvement of FEV1 at 6 months after EBV treatment. In the three
      patients with positive CV, the mean value of FEV1 decreased from 28.8+/-19.0% of
      predicted value before EBV treatment to 24.8+/-12.6% (P>0.05) at 1 month after
      EBV treatment, than to 22.1+/-10.8% (P>0.05) at 6 months after EBV treatment.
      CONCLUSIONS: EBV is an effective measure to treat highly selected COPD patients
      with giant bulla. Although, EBV treatment can achieve transient improvement of
      lung function at patients with CV negative bulla, long-term benefit was merely
      observed at the patient with a bulla at right middle lobe (RML).

PMID- 25589960
TI  - Effect of a neutrophil elastase inhibitor on ventilator-induced lung injury in
      rats.
AB  - OBJECTIVE: We hypothesized that pretreatment with sivelestat therapy could
      attenuate ventilator-induced lung injury (VILI) and lung inflammation in a rat
      model. METHODS: The neutrophil elastase inhibitor was administered
      intraperitoneally 30 min before and at the initiation of ventilation. The rats
      were categorized as (I) sham group; (II) VILI group; (III) sivelestat group; (IV)
      early sivelestat group. Wet-to-dry weight ratio, bronchoalveolar lavage fluid
      (BALF) neutrophil and protein, tissue malondialdehyde (MDA) and histologic VILI
      scores were investigated. RESULTS: The ratio of wet-to-dry weight, BALF
      neutrophil and protein, tissue MDA and VILI scores were significantly increased
      in the VILI group compared to the sham group [3.85+/-0.32 vs. 9.05+/-1.02,
      P<0.001; (0.89+/-0.93)*10(4) vs. (7.67+/-1.41)*10(4) cells/mL, P<0.001; 2.34+/
      0.47 vs. 23.01+/-3.96 mg/mL, P<0.001; 14.43+/-1.01 vs. 36.56+/-5.45 nmol/mg
      protein, P<0.001; 3.78+/-0.67 vs. 7.00+/-1.41, P<0.001]. This increase was
      attenuated in the early sivelestat group compared with the sivelestat group [wet
      to-dry ratio: 6.76+/-2.01 vs. 7.39+/-0.32, P=0.032; BALF neutrophil: (5.56+/
      1.13)*10(4) vs. (3.89+/-1.05)*10(4) cells/mL, P=0.021; BALF protein: 15.57+/-2.32
      vs. 18.38+/-2.00 mg/mL, P=0.024; tissue MDA: 29.16+/-3.01 vs. 26.31+/-2.58,
      P=0.049; VILI scores: 6.33+/-1.41 vs. 5.00+/-0.50, P=0.024]. CONCLUSIONS:
      Pretreatment with a neutrophil elastase inhibitor attenuates VILI in a rat model.

PMID- 25589961
TI  - Cost and effectiveness of video-assisted thoracoscopic surgery for clinical stage
      I non-small cell lung cancer: a population-based analysis.
AB  - BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is a minimally invasive
      alternative to conventional surgery (CS). We aimed to estimate the short-term
      cost-effectiveness of VATS vs. CS for clinical stage I non-small cell lung cancer
      (NSCLC-c-stage-I) patients from the payer's perspective (National Health
      Insurance). METHODS: We identified NSCLC-c-stage-I patients diagnosed and
      received surgery within 2007-2009 through a comprehensive population-based
      database containing cancer and death registries, and reimbursement data. The
      duration of interest was 1 year. We included potential confounding covariables
      through literature searching and our own experience, and used a propensity score
      to construct a 1:1 population for adjustment. RESULTS: Our study population
      constituted 966 patients. The mean hospital stay [days, standard deviation (SD)]
      were 14.4 [7] and 16.1 (7.7) for VATS and CS respectively (P=0.002). The mean
      cost (2013 USD) and survival (year) was $22,316 vs. $21,976 and 0.98 vs. 0.974
      for VATS vs. CS. The probability for VATS to be cost-effective (i.e., positive
      net benefit) was 0.49 & 0.56 at willingness-to-pay (WTP) 50,000 & 100,000
      USD/life-year, respectively. CONCLUSIONS: We provide the first empirical evidence
      that when compared to CS, VATS was potentially cost-effective in the short term
      (1 year) within the common WTP levels in Taiwan.

PMID- 25589962
TI  - Predictive risk factors for lymph node metastasis in patients with small size non
      small cell lung cancer.
AB  - BACKGROUND: Accurate clinical staging of non-small cell lung cancer (NSCLC) is
      essential for developing an optimal treatment strategy. This study aimed to
      determine the predictive risk factors for lymph node metastasis, including both
      N1 and N2 metastases, in clinical T1aN0 NSCLC patients. METHODS: We
      retrospectively evaluated clinical T1aN0M0 NSCLC patients who showed no
      radiologic evidence of lymph node metastasis, and who had undergone surgical
      pulmonary resection with systematic mediastinal node dissection or sampling at
      the First Affiliated Hospital of Zhejiang University between January 2011 and
      June 2013. Univariate and multivariate logistic regression analyses were
      performed to identify predictive factors for node metastasis. RESULTS:
      Pathologically positive lymph nodes were found in 16.2% (51/315) of the patients.
      Positive N1 nodes were found in 12.4% (39/315) of the patients, and positive N2
      nodes were identified in 13.0% (41/315) of the patients. Some 9.2% (29/315) of
      the patients had both positive N1 and N2 nodes, and 3.8% (12/315) of the patients
      had nodal skip metastasis. Variables of preoperative radiographic tumor size, non
      upper lobe located tumors, high carcinoembryonic antigen (CEA) levels and
      micropapillary predominant adenocarcinoma (AC) were identified as predictors for
      positive N1 or N2 node multivariate analysis. CONCLUSIONS: Pathologically
      positive lymph nodes were common in small size NSCLC patients with clinical
      negative lymph nodes. Therefore, preoperative staging should be performed more
      thoroughly to increase accuracy, especially for patients who have the larger
      size, non-upper lobe located, high CEA level or micropapillary predominant ACs.

PMID- 25589963
TI  - The protective effects of glutamine in a rat model of ventilator-induced lung
      injury.
AB  - BACKGROUND: The mortality rate of patients with acute respiratory distress
      syndrome (ARDS) is still high despite the use of protective ventilatory
      strategies. We sought to examine the pharmacological effects of glutamine (GLN)
      in a two-hit model of endotoxin-induced inflammation followed by ventilator
      induced lung injury (VILI). We hypothesized that the administration of GLN
      ameliorates the VILI. METHODS: Sprague-Dawley rats were anesthetized and given
      lipopolysaccharide (LPS) intratracheally as a first hit to induce lung
      inflammation, followed 24 h later by a second hit of mechanical ventilation (MV)
      with either low tidal volume (6 mL/kg) with 5 cmH2O of positive end-expiratory
      pressure (PEEP) or high tidal volume (22 mL/kg) with zero PEEP for 4 h. GLN or
      lactated Ringer's solution as the placebo was administered intravenously 15 min
      prior to MV. RESULTS: In the LPS-challenged rats ventilated with high tidal
      volume, the treatment with GLN improved lung injury indices, lung mechanics and
      cytokine responses compared with the placebo group. CONCLUSIONS: The
      administration of GLN given immediately prior to MV may be beneficial in the
      context of reducing VILI.

PMID- 25589964
TI  - Lung cancer staging: the value of PET depends on the clinical setting.
AB  - BACKGROUND: Although positron emission tomography (PET) imaging is widely
      recommended in the evaluation of patients with lung cancer, randomized controlled
      trials (RCTs) assessing this have demonstrated inconsistent results. We asked
      whether differences in the clinical context and endpoints could explain these
      discrepancies. METHODS: We used realist synthesis methods to analyze how
      contextual differences among RCTs affected the results. We focused on RCTs to
      minimize confounding yet permit evaluation of differences by comparing across
      studies. RESULTS: This analysis suggests that the impact of PET depends on the
      clinical setting. PET is of greatest benefit in identifying M1 disease in
      patients with a high chance of such involvement and when little traditional
      imaging [e.g., abdominal/pelvis computed tomography (CT) and bone scan] is used.
      Identification of N2,3 involvement by PET prior to resection is seen primarily
      when there is at least a moderate probability of such and the rate of invasive
      staging is high. The rate of N2 disease not identified preoperatively appears to
      increase if PET is used to avoid invasive mediastinal staging in clinical
      settings in which the risk of N2,3 involvement is moderately high. There is both
      a potential benefit in avoiding stage-inappropriate resection as well as a risk
      of missed (stage-appropriate) resection if PET findings are not evaluated
      carefully. CONCLUSIONS: A blanket recommendation for PET may be too simplistic
      without considering nuances of the clinical setting.

PMID- 25589965
TI  - Five-year epidemiological survey of valvular heart disease: changes in morbidity,
      etiological spectrum and management in a cardiovascular center of Southern China.
AB  - OBJECTIVE: The objective of the present study is to analyze the epidemiological
      profile of patients with abnormal valvular structure and function and highlight
      the etiological spectrum and management of valvular heart disease (VHD) in a
      single cardiovascular center of Southern China in five years. METHODS: The
      retrospective study included 19,428 consecutive patients (9,441 men and 9,987
      women with a mean age of 52.03+/-20.50 years) with abnormal valvular structure
      and function who were screened by transthoracic echocardiography (TTE) or
      transesophageal echocardiography (TEE) at the in-patient department of Guangdong
      General Hospital from January 2009 to December 2013. Data on baseline
      characteristics, potential etiology, treatment strategies and discharge outcomes
      were collected from electronic medical records. RESULTS: There were 13,549
      (69.7%) patients with relatively definite etiology for VHD. VHD was rheumatic in
      7,197 (37.0%) patients, congenital in 2,697 (13.9%), degenerative in 2,241
      (11.5%), ischemic in 2,460 (12.7%). The prevalence decreased significantly in
      rheumatic VHD from 2009 to 2013 (from 42.8% to 32.8%, P<0.001), but increased
      markedly in congenital VHD (from 9.0% to 12.3%, P<0.001), ischemic VHD (from 9.2%
      to 11.3%, P=0.003) and degenerative VHD (from 8.8% to 14.5%, P<0.001). Meantime,
      the prevalence of ischemic VHD increased after the age of 45, similar to that of
      degenerative VHD. From 2009 to 2013, the proportion of patients with VHD
      undergoing open cardiac valvular surgery decreased (from 49.5% to 44.3%, P<0.001)
      and that of patients treated with general medication increased (from 49.2% to
      54.1%, P<0.001). However, there was markedly increment in video-assisted
      thoracoscopic surgery (VATS) from 2009 to 2013 (from 0.3% to 4.4%, P<0.001).
      Increasing tendencies were showed in aortic mechanical valve replacement (from
      32.1% to 34.5%, P=0.001) and double mechanical valve replacement (from 20.9% to
      22.3%, P=0.035), especially in mitral valvuloplasty (from 8.5% to 15.7%,
      P<0.001). However, the proportion of patients undergoing bioprosthetic valve
      replacement decreased from 2009 to 2013 (from 26.3% to 15.5%, P<0.001).
      CONCLUSIONS: Despite a significant shift from rheumatic towards degenerative
      etiology from 2009 to 2013, rheumatic VHD remains the leading etiology in
      Southern China, with a significant increase in the prevalence of ischemic,
      congenital and degenerative VHD. General medication and cardiac valvular surgery
      remain the main treatment options. The proportion of VATS increased markedly from
      2009 to 2013, and mechanical valve replacement and mitral valvuloplasty showed an
      increasing tendency.

PMID- 25589966
TI  - Rapid pleurodesis is an outpatient alternative in patients with malignant pleural
      effusions: a prospective randomized controlled trial.
AB  - BACKGROUND: Chemical pleurodesis can be palliative for recurrent, symptomatic
      pleural effusions in patients who are not candidate for a thoracic surgical
      procedure. We hypothesized that effective pleurodesis could be accomplished with
      a rapid method of pleurodesis as effective as the standard method. METHODS: A
      prospective randomized 'non-inferiority' trial was conducted in 96 patients with
      malignant pleural effusion (MPE) who are not potentially curable and/or not
      amenable to any other surgical intervention. They were randomly allocated to
      group 1 (rapid pleurodesis) and to group 2 (standard protocol). In group 1,
      following complete fluid evacuation, talc slurry was instilled into the pleural
      space. This was accomplished within 2 h of thoracic catheter insertion, unless
      the drained fluid was more than 1,500 mL. After clamping the tube for 30 min, the
      pleural space was drained for 1 h, after which the thoracic catheter was removed.
      In group 2, talc-slurry was administered when the daily drainage was lower than
      300 mL/day. RESULTS: No-complication developed due to talc-slurry in two groups.
      Complete or partial response was achieved in 35 (87.5%) and 33 (84.6%) patients
      in group 1 and group 2 respectively (P=0.670). The mean drainage time was 40.7
      and 165.2 h in group 1 and group 2 respectively (P<0.001). CONCLUSIONS: Rapid
      pleurodesis with talc slurry is safe and effective and it can be performed in an
      outpatient basis.

PMID- 25589967
TI  - Overnight fluid shifts in subjects with and without obstructive sleep apnea.
AB  - OBJECTIVE: To investigate the characteristics of baseline body fluid content and
      overnight fluid shifts between non-obstructive sleep apnea (non-OSA) and
      obstructive sleep apnea (OSA) subjects. METHODS: A case-controlled study was
      performed between February 2013 and January 2014, with 36 (18 OSA and 18 non-OSA)
      outpatients enrolled in this study. Polysomnographic parameters and results of
      body fluid were compared between the two groups. RESULTS: There were no
      differences in age, weight, and body mass index (BMI) between groups. Compared
      with the non-OSA group, OSA group had significantly higher neck circumference
      (NC) and fluid volume shift in the legs. OSA patients had higher left and right
      leg fluid indices than non-OSA subjects. There were significant correlations
      between apnoea-hypopnoea index and baseline fluid indices in both legs as well as
      the reduction in overnight change in both legs fluid volume. The increase in NC
      was also significantly correlated with the reduction in overnight change in both
      legs fluid volume, but not with the change in head and neck fluid volume. There
      were significant correlations between change in NC and increased fluid shifts in
      head and neck volume. CONCLUSIONS: OSA patients had a higher baseline fluid
      content in both legs as compared with non-OSA subjects, which may be the basic
      factor with regards to fluid shifts in OSA patients. The increase in head and
      neck fluid shift volume did not directly correlate with the severity of OSA.

PMID- 25589968
TI  - The changes of vaccinia related kinase 1 in grafted heart after rat heart
      transplantation.
AB  - OBJECTIVE: To assess the expression and significance of vaccinia-related kinase 1
      (VRK1) after rat heart transplantation. MATERIALS AND METHODS: Lewis and Wistar
      rats weighing 250 to 300 g were used as donors and recipients. Allografts were
      from Wistar transplanted into Lewis, and isografts were transplanted from Lewis
      into Lewis. Grafts were harvested at 1, 3, 5, and 7 days after transplantation.
      We performed Western Blot of heart tissues after cardiac transplantation. To
      analyze VRK1 express between the isografts and allografts for immunohistochemical
      staining. At 5th day after heart transplantation use related cytokines VRK1 for
      immunohistochemical. We used double immunofluorescent staining on transverse
      cryosections of graft tissues by co-labeling with different markers, including
      those for VRK1, activate caspase-3, alpha-actinin, VCAM-1, CD4. RESULTS: Compared
      with rare expression in syngeneic Lewis rat hearts, VRK1 protein level in
      allogeneic hearts were detected at various survival times after heterotopic heart
      transplantation, which observably expressed on day 5 postoperative. In addition,
      we examined the expression of activate caspase-3 in allogeneic hearts, which has
      a similar expression with VRK1. Immunohistochemical and immunofluorescent method
      displayed that VRK1 was widely expressed in cytoplasm of cardiac tissue and
      activate caspase-3 was also expressed in cardiomyocytes. However, the VRK1 wasn't
      express in inflammation. CONCLUSIONS: The VRK1 expression has increased after
      heart transplantation in allograft and isograft, and VRK1 may play a significant
      role in myocardial apoptosis after heterotopic heart transplantation in rats.

PMID- 25589969
TI  - Uniportal video assisted thoracoscopic lobectomy: primary experience from an
      Eastern center.
AB  - BACKGROUND: Uniportal video-assisted thoracoscopic surgery (VATS) lobectomy is an
      emerging technique for the surgical resection of non-small cell lung cancer
      (NSCLC). Besides its wide debates on safety and efficacy throughout the world,
      there were few report on uniportal VATS from the Eastern countries. In this
      article, we summarized our primary experience on uniportal VATS lobectomy in an
      Eastern center. METHODS: From October 2013 till February 2014, 54 consecutive
      uniportal VATS lobectomy were performed in the Department of Thoracic Surgery,
      Zhongshan Hospital of Fudan University. Patients' clinical features and operative
      details were recorded. Post-operatively, the morbidity and mortality were
      recorded to analyze the safety and efficacy of uniportal VATS lobectomy for
      NSCLCs. RESULTS: Among the 54 planned uniportal VATS lobectomy, there was one
      conversion to mini-thoracotomy due to lymph node sticking. Extra ports were
      required in two patients. The uniportal VATS lobectomy was achieved in 51 out of
      54 patients (94.4%). The average operation duration was 122.2+/-37.5 min (90-160
      min). The average volume of estimated blood loss during the operation was 88.8+/
      47.1 mL (50-200 mL). The mean chest tube duration and hospital stay were 3.2+/
      1.9 days and 4.6+/-2.0 days, respectively. There was no postoperative mortality
      in this study. Two patients suffered from prolonged air leakage (5 and 7 days),
      and one atrial fibrillation was observed in this cohort. CONCLUSIONS: Based on
      our primary experience, uniportal VATS lobectomy is a safe and effective
      procedure for the surgical resection of NSCLCs. The surgical refinements and
      instrumental improvements would facilitate the technique. Further studies based
      on larger population are required to determine its benefits towards patients with
      NSCLCs.

PMID- 25589970
TI  - Differences in the clinical and radiological characteristics of lung-involved
      toxocariasis between toxocariasis with eosinophilia and those without
      eosinophilia.
AB  - BACKGROUND: Previously, most studies did not discuss about the characteristics of
      lung-involved toxocariasis without eosinophilia. However, the patients are not
      always accompanied by eosinophilia, so it is necessary to learn about the
      clinical and radiologic features that may predict pulmonary toxocariasis without
      eosinophilia. In addition, we also want to check the differences in
      characteristics between the two groups based on the presence of eosinophilia.
      METHODS: We investigated patients from October 2009 to February 2014 with
      antibody against Toxocara positive using enzyme-linked immunosorbent assay
      (ELISA), abnormal chest X-ray, and computed tomography (CT) findings. This
      retrospective study included patients diagnosed as toxocariasis with pulmonary
      involvement, using the results of laboratory findings, symptoms, and CT at the
      time of diagnosis. RESULTS: Out of 88 patients, 78% were male and 22% were
      female; and the mean age was 51 years. The mean eosinophil fraction in peripheral
      blood was 11.8%. The most common chest CT findings of patients with eosinophilia
      were nodules plus ground glass opacity (GGO) pattern, and nodules were found in
      patients with no eosinophilia. Pure GGO was the most common predominant subtype
      in GGO lesions of patients with eosinophilia. In terms of anatomical
      distribution, random distribution was seen more in patients with eosinophilia
      than those without eosinophilia, with statistically significance (P=0.042). In
      patients who underwent additional CT scans, 44% of those with eosinophilia had
      migrating lesions and had significant differences from patients without
      eosinophilia (P=0.008). CONCLUSIONS: There were no significant differences in
      lesion characteristics with the exception of random anatomic distribution between
      patients with and without eosinophilia. However, there was a significant
      difference between the fixation and migration of the lesion in patients with and
      without eosinophilia.

PMID- 25589971
TI  - Antihypertensive therapy with nicardipine for patients with aortic disease is
      associated with more esmolol usage than urapidil.
AB  - BACKGROUND: Acute aortic disease is a common but challenging entity in clinical
      practice. Titration the blood pressure and heart rate to a target level is of
      paramount importance in the acute phase regardless of whether the patient will
      undergo a surgery or not eventually. In addition to the initially intravenous
      beta-blockers, parenteral infusion of nicardipine and urapidil are the most
      common used antihypertensive therapy currently in mainland China. However, few
      empirical data was available with respect to the different effect on patients'
      outcome of the two antihypertensive strategies. Specifically given the
      deleterious reflex tachycardia of vasodilators which may increase force of
      ventricular contraction and potentially worsen aortic disease. Therefore, this
      study was aimed to evaluate the difference of the abovementioned two
      antihypertensive strategies on the outcome of patients with aortic disease.
      METHODS: All patients with new diagnosed aortic diseases presented to our
      hospitals from January 1, 2013 to June 30, 2014 were retrospectively reviewed.
      The antihypertensive strategies and their association with patients' outcomes
      were evaluated with logistics regression. RESULTS: A total of 120 patients with
      new diagnosed aortic disease were included in the study. Of them, 47 patients
      received urapidil while 73 patients received nicardipine antihypertensive
      therapy. Patients with nicardipine were more quickly to reach the target blood
      pressure level than those treated with urapidil (median, 18 vs. 35 min, P=0.024).
      After adjustment for patient demographics, co-morbidity, involved extend of
      aorta, interventional strategies, antihypertensive therapy with nicardipine (with
      urapidil as reference) for patients with aortic disease was significantly
      associated with high esmolol cost [odds ratio (OR): 6.2, 95% confidence interval
      (CI), 1.8-21.6, P=0.004] and longer ICU length of stay (LOS) (OR: 3.9, 95% CI,
      1.5-10.3, P=0.006). However, there was no significant correlation between
      nicardipine use and ICU mortality (OR: 0.3; 95% CI, 0.1-1.4, P=0.123).
      CONCLUSIONS: Although nicardipine achieved the target blood pressure level more
      quickly than urapidil for patients with aortic disease, it was associated with
      more esmolol use and longer ICU LOS.

PMID- 25589972
TI  - In vitro study of coronary flow occlusion in transcatheter aortic valve
      implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been developed
      recently for patients with high morbidities and who are believed to be not
      tolerate standard surgical aortic valve replacement. Nevertheless, the TAVI is
      associated with complications such as potential obstruction of coronary ostia,
      mitral valve insufficiency, and stent migration although it seems promising.
      Impairment of the coronary blood flow after TAVI is catastrophic and it was
      believed to be associated with the close position of the coronary orifice and the
      aortic leaflets and valve stent. However, few data was available as to the
      anatomic relationship between valve stent and aortic root anatomic structures
      including the coronary arterial ostia, aortic leaflets. METHODS: The aortic roots
      were observed in 40 hearts specimens. The width of aortic leaflet, height of
      aortic sinus annulus to the sinutubular junction (STJ), distance between aortic
      sinus annulus to its corresponding coronary ostia, and coronary arterial ostia to
      its corresponding STJ level were measured. Moreover, the relationships of valve
      stent, aortic leaflets and coronary ostia before/post stent implantation and
      after the open of aorta were evaluated respectively. RESULTS: Approximate three
      quarters of the coronary ostia were located below the STJ level. The mean
      distances from left, right and posterior aortic sinus annulus to the related STJ
      level was comparable, which was 18.5+/-2.7, 18.9+/-2.6, 18.7+/-2.6 mm,
      respectively. Meanwhile, the height of left and right aortic sinus annulus to its
      corresponding coronary ostia was 16.6+/-2.8 and 17.2+/-3.1 mm for left and right
      side respectively. CONCLUSIONS: Most of the coronary ostia were located below the
      STJ level and could be covered by the leaflets. This highlights the need of
      modified stents to prevent occlusion of coronary flow after TAVI.

PMID- 25589973
TI  - Adrenergic regulation of the rapid component of delayed rectifier K+ currents in
      guinea pig cardiomyocytes.
AB  - BACKGROUND: Guinea pig ventricular cardiomyocytes display the rapid component of
      the delayed rectifier potassium current (Ikr) that contributes to ventricular
      repolarization and promotes stress-induced arrhythmias. Adrenergic stimulation
      favors ventricular arrhythmogenesis but its effects on Ikr are poorly understood.
      METHODS: Adrenergic modulation of Ikr was studied in isolated guinea pig
      ventricular cardiomyocytes using whole-cell patch clamping. RESULTS: We found
      that the Ikr amplitude was reduced to 0.66+/-0.02 and 0.62+/-0.03 in response to
      0.1 uM phenylephrine (PE), an alpha1AR agonist, and 10 uM isoproterenol (ISO), a
      betaAR agonist, respectively. The effect of PE can be blocked by the selective
      alpha1A-adrenoceptor antagonist 5-methylurapidil, but not by the alpha1B
      adrenoceptor antagonist chloroethylclonidine or alpha1D-adrenoceptor antagonist
      BMY7378. Additionally, the effect of ISO can be blocked by the beta1-selective AR
      antagonist CGP-20712A, but not by the beta2-selective AR antagonist ICI-118551.
      Although PE and ISO was continuously added to cells, ISO did not decrease the
      current to a greater extent when cells were first given PE. In addition, PE's
      effect on Ikr was suppressed by beta1AR stimulation. CONCLUSIONS: Ikr can by
      regulated by both the alpha1 and beta ARs system, and that in addition to direct
      regulation by each receptor system, crosstalk may exist between the two systems.

PMID- 25589975
TI  - Sodium tanshinone IIA silate as an add-on therapy in patients with unstable
      angina pectoris.
AB  - OBJECTIVE: To investigate whether sodium tanshinone IIA silate (STS) as an add-on
      therapy to conventional treatment may provide additional benefits for patients
      with unstable angina pectoris (UAP) and is associated with changes in profiles of
      serum inflammatory factors. METHODS: Eighty patients diagnosed with UAP were
      randomly divided into two groups for the 2-week treatment. The control group
      received conventional therapy, while the treatment group was given intravenous
      STS (0.06 mg in 250 mL, once daily) as an add-on therapy to the conventional
      medications. The therapeutic efficacy and changes in serum levels of several
      inflammatory cytokines, including monocyte chemotactic protein 1 (MCP-1), tumor
      necrosis factor alpha (TNF-alpha), peroxisome proliferator-activated receptor
      (PPAR-gamma), and high-sensitivity C-reactive protein (hs-CRP) from baseline were
      determined and compared between the two group. RESULTS: The clinical symptoms of
      all patients in both groups were improved after treatment. The overall rate of
      effectiveness was 97.5% in the treatment group vs. 80.0% in the control group.
      Serum levels of MCP-1, TNF-alpha, and hs-CRP levels were significantly reduced in
      both groups (P<0.01), whereas the reduction was greater in patients receiving
      additional STS (P<0.05). PPAR-gamma was significantly elevated in both groups
      (P<0.01). CONCLUSIONS: STS in combination with conventional treatment may be
      associated with better outcomes in patients with UAP.

PMID- 25589974
TI  - Epidemiological and viral genome characteristics of the first human H7N9
      influenza infection in Guangdong Province, China.
AB  - BACKGROUND: The first H7N9 human case in south of China was confirmed in
      Guangdong Province on August 2013, outside of the typical influenza season. For
      investigating the H7N9 virus source and transmission in the local community, we
      analyze the epidemiology and genome features of the virus isolated from the first
      human infection detected in Guangdong Province. METHODS: The data including
      medical records, exposure history and time line of events for the H7N9 patient
      and close contacts was collected. Variation and genetic signatures of H7N9 virus
      in Guangdong was analyzed using ClustalW algorithm and comparison with mutations
      associated with changes in biological characteristics of the virus. RESULTS: The
      female patient had a history of poultry exposure, and she was transferred from a
      local primary hospital to an intensive care unit (ICU) upon deterioration. No
      additional cases were reported. Similar to previous infections with avian
      influenza A (H7N9) virus, the patient presented with both upper and lower
      respiratory tract symptoms. Respiratory failure progressed quickly, and the
      patient recovered 4 weeks after the onset of symptoms. Genome analysis of the
      virus indicated that the predicted antigen city and internal genes of the virus
      are similar to previously reported H7N9 viruses. The isolated virus is
      susceptible to neuraminidase (NA) inhibitors but resistant to adamantine.
      Although this virus contains some unique mutations that were only detected in
      avian or environment-origin avian influenza A (H7N9) viruses, it is still quite
      similar to other human H7N9 isolates. CONCLUSIONS: The epidemiological features
      and genome of the first H7N9 virus in Guangdong Province are similar to other
      human H7N9 infections. This virus may have existed in the environment and live
      poultry locally; therefore, it is important to be alert of the risk of H7N9 re
      emergence in China, including emergence outside the typical influenza season.

PMID- 25589976
TI  - Lung protective effects of budesonide nebulization during perioperative period of
      thoracolumbar fusion.
AB  - OBJECTIVE: To determine the pulmonary protective effect of budesonide
      nebulization in patients undergoing spinal fusion for thoracolumbar degenerative
      disorders. METHODS: Forty patients who underwent spinal fusion at our hospital
      from January 2013 to December 2013 for the treatment of thoracolumbar
      degenerative disorders were randomly allocated into a budesonide intervention
      group (budesonide group) and a control group. The control group received routine
      supportive therapy including rehydration, analgesia, and neurotrophic drug
      treatment; in addition to these, the budesonide group was administered with
      budesonide nebulization (1-mg budesonide/2-mL saline, twice daily) from 1 day
      preoperatively through 3 days postoperatively. Respiratory symptoms, arterial
      blood gas, and pulmonary complication before and after the operations were
      observed and compared between the two groups. RESULTS: The patients ranged in age
      from 46 to 81 years old (mean, 62.4+/-9.4 years), and comprised 20 men and 20
      women. There were no significant differences in postoperative body temperature,
      heart rate, and respiratory rate between the groups (P>0.05). The change in
      arterial partial pressure of oxygen (PaO2) from baseline was significantly lower
      in the budesonide group than in the control group (at 2.4+/-12.4 vs. 16.0+/-11.3
      mmHg) (P=0.002), so was the findings for oxygen saturation (SpO2) (0.2%+/-2.3%
      vs. 2.6%+/-3.3%), respectively (P=0.047). The incidence of postoperative
      pulmonary symptoms and complications, such as coughing, shortness of breath, and
      dyspnea, was 0% in the budesonide group and 15% in the control group; overall,
      the budesonide group performed better than control group in all pulmonary
      parameters. None of the patients in the budesonide group experienced severe
      events associated with glucocorticoid therapy. CONCLUSIONS: Perioperative
      budesonide nebulization may reduce the postoperative pulmonary complications in
      middle-aged and elderly patients undergoing thoracolumbar fusion to treat
      thoracolumbar degeneration, with favorable efficacy and safety.

PMID- 25589977
TI  - Chemotherapy with paclitaxel plus carboplatin for relapsed advanced thymic
      carcinoma.
AB  - OBJECTIVE: For rarity of thymic carcinoma, no definitive chemotherapeutic regimen
      has been established in second- or further-line settings. The aim of this study
      was to evaluate the feasibility and safety of paclitaxel plus carboplatin in
      advanced thymic carcinoma as second- or further-line treatment in our institute.
      METHODS: We evaluated the efficacy and toxicity of paclitaxel plus carboplatin as
      salvage therapy in 12 patients with previously treated advanced thymic carcinoma
      from 2005 to 2012 in Zhejiang Cancer Hospital. Survival analysis was evaluated by
      Kaplan-Meier method. RESULTS: Twelve patients were included in current study.
      Four patients achieved stable disease (SD), and three achieved partial response
      (PR), representing a response rate of 25.0% and disease control rate (DCR) of
      58.3%. Median progression-free survival (PFS) and overall survival (OS) were 3.5
      and 24.0 months, respectively. The toxicities associated with the paclitaxel plus
      carboplatin was generally acceptable. CONCLUSIONS: Paclitaxel plus carboplatin
      appears to have some activity against thymic carcinoma as second-line or later
      chemotherapy in advanced thymic carcinoma.

PMID- 25589978
TI  - Video-assisted thoracoscopic left upper lobe sleeve lobectomy combined with
      pulmonary arterioplasty via two-port approach.
AB  - Here we report a case of left upper lobe sleeve lobectomy with pulmonary
      arterioplasty via video-assisted thoracoscopy surgery (VATS) two-port approach. A
      squamous cell carcinoma with stage T3N1M0 was identified on pathological
      examination. The bronchial anastomosis was performed using running suture with a
      3-0 prolene. Two bulldog clamps were used to gain adequate vascular control.
      Partial pulmonary artery resection was achieved tangentially with a stapler. The
      postoperative course was uneventful. 

PMID- 25589979
TI  - Total thoracoscopic combined lingulectomy and pericardial cystectomy.
AB  - Thoracoscopic anatomic segmentectomy is usually more complex than lobectomy. This
      video shows a 58-year-old female who suffered from limited bronchiectasis of the
      lingular segment of the left upper lung and a pericardial cyst on the same side.
      Both of these benign thoracic diseases can cause pleural adhesions. Repeated
      chronic inflammation contributes to hypervascularity and lymph node enlargement,
      making surgery more difficult. We used single-direction thoracoscopic
      segmentectomy via a three-port approach and successfully removed the lingula and
      pericardial cyst. 

PMID- 25589980
TI  - Video-assisted thoracoscopic surgery right upper posterior segmentectomywith
      systemic mediastinal lymph node dissection.
AB  - Video-assisted thoracoscopic surgery (VATS) segmentectomy is a promising
      treatment option for rigorously selected patients with earlystage non-small cell
      lung cancer. In the presented video, a 66-year-old male with a 1.6 cm suspicious
      nodule located at the posterior segment of the right upper lobe was treated with
      anatomic segmentectomy and systemic mediastinal lymph node (LN) dissection
      successfully. 

PMID- 25589981
TI  - Video-assisted thoracoscopic left upper lobe apical trisegmentectomy with the
      Harmonic scalpel.
AB  - Segmental resection is a useful procedure to preserve respiratory function. A 56
      year-old woman presented with a finding of a left upper lobe lesion on CT
      scanning. She was performed video-assisted thoracoscopic left upper lobe apical
      trisegmentectomy with the Harmonic scalpel. Video-assisted thoracoscopy surgery
      (VATS) segmentectomy is associated with safe and feasible procedure. With the
      Harmonic scalpel dissection, blood loss is minimal and this speeds patient
      recovery. 

PMID- 25589982
TI  - Left lower sleeve lobectomy and systematic lymph node dissection by complete
      video-assisted thoracic surgery.
AB  - Sleeve lobectomy for selected cases of central lung cancer has better functional
      outcomes comparing to pneumonectomy. With improved technology and increased
      experiences in complete video-assisted thoracic surgery (VATS) lobectomy,
      complete VATS sleeve lobectomy has been applied in major medical centers
      recently. A 64-year-old male patient with left lower central lung cancer
      underwent thoracoscopic sleeve lobectomy and systemic mediastinal lymph node
      dissection. The major incision, of four incisions in total, was a 4 cm mini
      incision in the 4th intercostal space of anterior axillary line. The patient had
      recovered uneventfully after the surgery. 

PMID- 25589983
TI  - Video-assisted thoracic surgery right sleeve lobectomy.
AB  - A 50-year-old active male with a smoking history of 30 years (20 cigarettes per
      day) was admitted to hospital because of more than one month's cough without
      sputum. No comorbidity was present. The preoperative examination showed: blood
      test normal, ECG normal, cardio-pulmonary function normal, chest computed
      tomography (CT) display right upper lobe (RUL) mass of 5 cm diameter.
      Bronchoscopy examination and biopsy indicated large cell neuroendocrine carcinoma
      (LCNEC) in the take-off of RUL bronchus. No metastatic focus was found after
      emission computed tomography (ECT) scan of whole body bone, abdominal US scanning
      and brain MR. After initial evaluation, the clinical stage before operation was
      cT2bN0M0 (IIA stage). A selective video-assisted thoracic surgery (VATS)
      operation was arranged after 9 days of smoking cessation. Lateral position, one
      10 mm trocar for camera in the 7th intercostals space in the mid-auxiliary line,
      4 cm trocar for operation in the 4th intercostal space in the anterior axillary
      line, 15 mm trocar for auxiliary operation in the 8th intercostal space in the
      scapula line, the patient received VATS RUL lobectomy, plus systemic mediastinal
      lymph nodes dissection. The procedure of 200 minutes operation was smooth with
      blood loss of about 150 mL. Chest tube was removed 6 days after operation, and
      the patient discharged 11 days after the operation; The post-operation
      pathological examination showed RUL LCNEC, and the pathological stage was
      pT2bN0M0R0 (IIA stage). The patient has received four cycles of EP adjuvant
      chemotherapy per 21 days and is still alive without disease recurrence and
      metastasis after re-examination. 

PMID- 25589984
TI  - Uniportal video-assisted thoracoscopic left basilar segmentectomy.
AB  - Uniportal video-assisted thoracoscopic surgery (VATS) has recently been
      introduced as an acceptable alternative to the traditional three-port VATS.
      Uniportal VATS lobectomy and segmentectomy actually gained increasing popularity.
      Until now there have been few reports about uniportal VATS basilar segmentectomy;
      we herein reported our experience with a patient who suffered from recurrent
      hemoptysis with 1-cm nodule in the basilar segment of the left lower lobe. A left
      basilar segmentectomy was performed through a single port. Operating time was 90
      minutes, and postoperative course was uneventful. Pathology revealed
      cryptococcosis. Follow-up at 6 months after surgery demonstrated a normal chest
      computed tomographic (CT) scan and complete recovery without complications. 

PMID- 25589985
TI  - Video-assisted thoracic surgery left S1+2+3 segmentectomy for lung cancer.
AB  - A 49-year-old female presented with a solitary pulmonary nodule on the chest
      screening computed tomography (CT) scan. The nodule was 1.3 cm in diameter and
      located in the apical segment of left upper lobe. The lesion was considered to be
      cT1aN0M0 non-small cell lung cancer (NSCLC) and a 3-port video-assisted thoracic
      surgery (VATS) wedge resection was performed. Intraoperative frozen sections
      revealed a lung adenocarcinoma. Therefore, sequential S1+2+3 segmentectomy of the
      left upper lobe was performed, also systematic lymph node dissection was carried
      out. The final pathological stage was pT1aN0M0 (Ia). 

PMID- 25589986
TI  - Uniportal video-assisted thoracoscopic surgery right upper lobectomy with
      systematic lymphadenectomy in a semiprone position.
AB  - A 53-year-old male smoker was referred to our hospital with an enlarged lesion in
      the right upper lung. Computed tomography (CT) showed a 1.5 cm solid lesion with
      pleural indentation in the right upper lobe adjacent to the oblique fissure. The
      preoperative clinical diagnosis was stage I primary lung cancer. Uniportal video
      assisted thoracoscopic surgery (VATS) right upper lobectomy in a semiprone
      position was performed in this case. Frozen section examination confirmed the
      diagnosis of lung adenocarcinoma, and systematic lymphadenectomy was then
      performed. A chest tube was placed at the posterior part of the incision through
      the dorsal thoracic cavity to the apex. The postoperative pathologic diagnosis
      was T2aN0M0 adenocarcinoma. 

PMID- 25589987
TI  - Unidirectionally progressive resection of left upper pulmonary lobe under video
      assisted thoracoscopy.
AB  - The case is a nodule in the upper left lobe, and intraoperative frozen section
      pathological diagnosis on the removed nodule confirmed well differentiated
      mucinous adenocarcinoma. Unidirectionally progressive resection of the left upper
      pulmonary lobe under video-assisted thoracoscopy is selected as the surgical
      method. Right below the operation hole, surgeons gradually advanced in one
      direction, and dissociated and divided in such order: the upper left pulmonary
      vein, the upper left lobe bronchus, the upper left pulmonary arterial branches
      and the fissures. Endoscopic linear cutters and hem-o-lok clip applicator were
      used to deal with the blood vessels, bronchus, and under-differentiated fissures.
      At last, the removed upper left lobe was put into a size eight sterile glove and
      taken out through the main operation hole. General anesthesia with double-lumen
      endotracheal intubation is used. The patient took a 90 degree decubitus on his
      contralateral side. The surgeons were on the ventral side of the patient, and
      operated with endoscope apparatus under the monitor. 

PMID- 25589988
TI  - Video-assisted thoracic surgery left upper lobectomy with systematic
      lymphadenectomy.
AB  - A 43-year-old man was referred to our hospital after chest computed tomography
      revealed a 2.5-cm mixed ground-glass opacity peripherally in the left upper lobe
      of the lung. No metastasis or contraindication for surgery was found. Video
      assisted thoracic surgery (VATS) left upper lobectomy was performed, and analysis
      of the intraoperative frozen section confirmed the diagnosis of adenocarcinoma.
      Subsequently, systematic lymphadenectomy was performed. By using this method,
      suction and harmonic scalpel were the only two major instruments needed
      throughout the operation. The use of suction ensures a clear view, and the
      harmonic scalpel functions as a combined dissector, grasper, and cutter, which
      helps avoid changing instruments during the surgery and saves time. Moreover, the
      use of this technique for three-port VATS lobectomy facilitates the conversion
      into single-port VATS if needed. 

PMID- 25589989
TI  - Autogenous rib graft for reconstruction of sternal defects.
AB  - Those who have undergone sternum resection need graft to stabilize the sternum
      with steel wire, titanium mesh or polypropylene mesh. The current study reports a
      case of using autogenous rib graft to reconstruct the sternum after resection. A
      53-year-old man, whose chest computed tomography (CT) identified expansive
      lesions and the presence of osteocytes lesions in the sternum, with no apparent
      involvement of the mediastina structures, come to our medical center due to pain
      and a lump of the anterior chest wall. The patient underwent tumor radical
      resection and sternal reconstruction with autogenous rib graft, and the
      histopathological examination of the surgical specimen determined the diagnosis
      of osteosarcoma. The patient has recovered well after the surgery. 

PMID- 25589990
TI  - VATS right upper lobectomy.
AB  - A 56-year-old male patient was admitted due to one small pulmonary nodule in the
      apicoposterior segment of the right upper lobe, which was found on his health
      screening one month ago. Preoperative examinations showed no distant metastasis,
      and his heart and lung functions could tolerate the lobectomy. Chest computed
      tomography (CT) showed one small pulmonary nodules on the apicoposterior segment
      of the right upper lobe, which was considered to be malignant lesions. No
      remarkably swollen lymph node was visible in the mediastinum. Therefore, VATS
      right upper lobectomy was performed and intraoperative frozen section confirmed
      the diagnosis of adenocarcinoma. 

PMID- 25589991
TI  - Thoracoscopic left upper lobectomy with systematic lymph nodes dissection under
      left pulmonary artery clamping.
AB  - Video-assisted thoracoscopic surgery (VATS) has become a routine procedure for
      stage I and II lung cancers. However, in the presence of multiple metastasized
      lymph nodes invading the pulmonary artery or its major branches, the pulmonary
      artery have to be resected partially or sleeve resected, which could be extremely
      risky under thoracoscopic conditions. In order to reduce the risk of bleeding, an
      experienced thoracic surgeon would occlude the inflow and outflow of the
      pulmonary artery before anatomically dissecting the area of the pulmonary artery
      with tumor invasion. Different centers may use different clamping techniques and
      devices. Here, we report our technique of totally thoracoscopic left upper
      lobectomy with systematic lymph nodes dissection under pulmonary artery clamping
      for a 49-year-old woman with left upper lobe carcinoma. The video demonstrates
      our thinking and surgical process. 

PMID- 25589992
TI  - Thoracoscopic resection of functional posterior mediastinal paraganglioma: a case
      report.
AB  - A 48-year-old man with posterior mediastinal mass was diagnosed as functional
      mediastinal paraganglioma during surgical exploration via open thoracotomy in
      another hospital. The operation was terminated because of severe hypertension
      when touching the tumor. He was transferred to our center later. After systemic
      evaluation, the patient was medicated with oral alpha- and beta-blockades, as
      well as intravenous fluid resuscitation for two weeks. His blood pressure became
      stable and a second operation was planned. The tumor was removed completely via
      the thoracoscopic approach, and was finally confirmed as functional paraganglioma
      by immunohistochemistry. The patient recovered uneventfully after surgery, with
      no recurrence during one year follow-up visit. 

PMID- 25589993
TI  - Optimization of lymph node dissection with VATS right upper lobectomy.
AB  - Video-assisted thoracoscopic lobectomy (VATSL) has developed rapidly. As per the
      requirements of tumor staging and oncotherapy, the technique of VATS mediastinal
      lymph node dissection plays an important role. With our experience, lymph node
      dissection can be performed very well on the condition that surgical process and
      skills be optimized. 

PMID- 25589995
TI  - Basic statistics (the fundamental concepts).
AB  - An appreciation and understanding of statistics is import to all practising
      clinicians, not simply researchers. This is because mathematics is the
      fundamental basis to which we base clinical decisions, usually with reference to
      the benefit in relation to risk. Unless a clinician has a basic understanding of
      statistics, he or she will never be in a position to question healthcare
      management decisions that have been handed down from generation to generation,
      will not be able to conduct research effectively nor evaluate the validity of
      published evidence (usually making an assumption that most published work is
      either all good or all bad). This article provides a brief introduction to basic
      statistical methods and illustrates its use in common clinical scenarios. In
      addition, pitfalls of incorrect usage have been highlighted. However, it is not
      meant to be a substitute for formal training or consultation with a qualified and
      experienced medical statistician prior to starting any research project. 

PMID- 25589994
TI  - Nonintubated anesthesia for thoracic surgery.
AB  - Nonintubated thoracic surgery has been used in procedures including pleura, lungs
      and mediastinum. Appropriate anesthesia techniques with or without sedation allow
      thoracic surgery patients to avoid the potential risks of intubated general
      anesthesia, particularly for the high-risk patients. However, nonintubated
      anesthesia for thoracic surgery has some benefits as well as problems. In this
      review, the background, indication, perioperative anesthetic consideration and
      management, and advantages and disadvantages are discussed and summarized. 

PMID- 25589996
TI  - A synopsis of resampling techniques.
AB  - Bootstrap is a computer intensive technique of resampling with replacement, which
      can be applied in many statistical analytical tests. The article describes the
      most frequent situations where bootstrap resampling can be applied in thoracic
      surgical research: variable selection for multivariable regression analysis,
      internal validation of regression equations, model validation. Practical examples
      for programming bootstrap in commercially available statistical software are
      finally reported. 

PMID- 25589997
TI  - Professor I-wen Wang: better life supported through mechanical circulatory
      devices-a dream within reach.

PMID- 25589998
TI  - Professor Mario Cazzola: prospect of the COPD medicine.

PMID- 25589999
TI  - Buyer beware: understanding the assumptions behind health economic assessments in
      personalized cancer care.

PMID- 25590000
TI  - Pyrexia in patients with uncontrolled systemic hypertension: could they have an
      aortic dissection?
AB  - Aortic dissection can present in a variety of ways and one of the most documented
      risk factors includes systemic hypertension. Occasionally aortic dissection can
      be diagnosed late due to an insidious presentation. Fever has been described in
      people with aortic dissection but rarely as the main presenting feature. We
      present the cases of two patients with type B aortic dissections who shared three
      pertinent features which could have alerted the clinicians of the potential
      diagnosis; systemic hypertension, small left sided pleural effusion and a fever
      of unknown origin. 

PMID- 25590001
TI  - Primary synovial sarcoma of the lung: can haemothorax be the first manifestation?
AB  - Primary pulmonary synovial sarcomas represent a rare clinical entity and account
      for approximately 0.5% of lung malignancies. We report the case of a 30-year-old
      male who presented clinically with haemothorax. Imaging revealed a complex
      collection obscuring a multi-lobulated mass in the right lower lobe of the lung.
      He underwent a right thoracotomy for evacuation of collection and surgical
      resection of his pulmonary mass. Histological analysis confirmed a grade 3
      monophasic fibrous synovial sarcoma of the lung with infiltration to adjacent
      pleura, causing his initial haemothorax. Postoperative period was uneventful and
      patient was referred to the oncology team for further management. Primary
      pulmonary synovial sarcoma, though rare, should remain an important differential
      when considering lung malignancies, as complete surgical resection is the
      mainstay of treatment. 

PMID- 25590002
TI  - Palliative stent graft placement combined with subsequent open surgery for
      retrograde ascending dissection intra-thoracic endovascular aortic repair.
AB  - Thoracic endovascular aortic repair (TEVAR) is an effective strategy for type B
      dissection. Retrograde ascending dissection (RAD) intra-TEVAR is a rare
      complication on clinic. In this case, a 48-year-old Chinese man with Stanford
      type B aortic dissection suffered acute RAD during the TEVAR. And palliative
      stent grafts placement was performed in a local hospital, which earned the time
      for transfer and subsequent total arch replacement surgery in Zhongshan Hospital
      Fudan University. This report suggests that the palliative strategy may be an
      option for RAD in some specific situation. 

PMID- 25590003
TI  - Induced airway obstruction under extracorporeal membrane oxygenation during
      treatment of life-threatening massive hemoptysis due to severe blunt chest
      trauma.
AB  - Simultaneous improvement in respiratory maintenance and bleeding control
      increases survival of patients with life-threatening hemoptysis. Endobronchial
      blockade is an effective method and is preferred for emergency hemostasis.
      However, when the volume of hemoptysis is high, emergency hemostasis and airway
      maintenance are impossible due to flooding of blood into the airway. We used
      extracorporeal membrane oxygenation (ECMO) to overcome these limitations in a
      patient with massive hemoptysis due to severe blunt trauma and succeeded in
      saving the life by inducing a near-total airway obstruction. 

PMID- 25590004
TI  - Unexpectedly long intravenous and intracardiac extension of a small-sized
      pulmonary pleomorphic carcinoma.
AB  - Pleomorphic carcinoma of the lung is one of the uncommon histological types of
      lung cancers, which shows an aggressive behavior. Intravenous extension (not
      metastasis or direct invasion) of the tumor into the heart is a rare complication
      of lung cancers. We present a case of a 64-year-old man, who was admitted to
      hospital due to severe dyspnea. Chest CT scan revealed a 2-cm nodule in the upper
      lobe of the right lung. Echocardiography demonstrated a giant mass in the left
      atrium. Because of a considerable distance between the lung nodule and heart, the
      relation of these two lesions was unclear. He died four days after the admission.
      At autopsy, the lung nodule was pleomorphic carcinoma composed of spindle and
      giant cells, which invaded the pulmonary vein and extended intravenously to the
      left atrium. The intravenous component of the tumor measured approximately ten cm
      in length. At the tip of the extension, an 8 cm * 5 cm * 3 cm mass was formed in
      the left atrium, which obstructed the mitral valve. This case highlights a
      possibility that even a small-sized, peripherally located pleomorphic carcinoma
      of the lung could extend for an unexpectedly long distance to the heart, causing
      cardiac complications. 

PMID- 25590005
TI  - Beware of arteria lusoria during lymph node dissection of the right paratracheal
      fossa for lung cancer surgery.
AB  - An asymptomatic elderly woman presented with a solitary right upper lobe mass
      revealed to be non-small cell lung cancer following routine surveillance post
      mastectomy. Upon review of CT with contrast in preparation for rigid bronchoscopy
      and right upper lobectomy, we noticed that the patient had a rare case of arteria
      lusoria. This is the presence of an aberrant right subclavian artery extending
      from the left side of the aortic arch, crossing posteriorly across the midline to
      supply the upper limb. We suggest that with a documented 100% diagnostic
      sensitivity on 64 multislice computed tomography, the presence of arteria lusoria
      within the posterior paratracheal fossa may cause life-threatening complications
      in the unaware during systematic lymph node dissection for non-small cell lung
      cancer (NSCLC). 

PMID- 25590006
TI  - Fatal interstitial lung disease associated with icotinib.
AB  - The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and
      erlotinib is drug-associated interstitial lung disease (ILD), which has been
      often described. However, it has been less well described for icotinib, a similar
      orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old
      female patient with stage IV lung adenocarcinoma who developed fatal ILD is
      reported here. She denied chemotherapy, and received palliative treatment with
      icotinib (125 mg po, three times daily) on March 1, 2013. One month after
      treatment initiation, the patient complained of continuous dry cough and rapid
      progressive dyspnea. Forty one days after icotinib treatment, icotinib associated
      ILD was suspected when the patient became increasingly dyspnoeic despite of
      treatment of pericardial effusion, left pleural effusion and lower respiratory
      tract infection, and X-ray computed tomography (CT) of chest revealed multiple
      effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib
      was discontinued and intravenous corticosteroid was started (methylprednisolone
      40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after
      icotinib treatment, the patient died of hypoxic respiratory failure. ILD should
      be considered as a rare, but often fatal side effect associated with icotinib
      treatment. 

PMID- 25590007
TI  - Primary malignant pericardial mesothelioma-a rare cause of superior vena cava
      thrombosis and constrictive pericarditis.
AB  - Primary malignant pericardial mesothelioma (PMPM) is an extremely rare, highly
      lethal and often misdiagnosed tumor. We report a 60-year-old woman complaining of
      dry cough, shortness of breath and exertional dyspnea due to a large pericardial
      effusion. The pericardial fluid volume declined after pericardiocentesis;
      analysis of the fluid revealed malignant cells and was negative for tuberculosis.
      Subsequently, the patient developed a compression of the superior vena cava and
      pericardial constriction. The patient's symptoms marginally improved after
      partial pericardiectomy, and a diagnosis of pericardial mesothelioma was made on
      pathology. However, her symptoms continued to aggravate, and she died 8 months
      after presentation. Pericardial mesothelioma should be discovered earlier to
      treat patients who develop repeatedly pericardial effusion after
      pericardiocentesis and pericardial tamponade or those develop constrictive
      pericarditis. 

PMID- 25590008
TI  - IgG4-related lung disease with atypical CT imaging: a case report.
AB  - IgG4-related lung disease is a rare disease, diagnosed when typical pathologic
      features are seen in the context of increased serum levels of IgG4 and the
      elevated tissue's IgG4-positive plasma cells. Here we reported the case of a 24
      year-old woman with IgG4-related lung disease. This patient presented with fever,
      cough and shortness of breath. Thoracic computed tomography (CT) images
      demonstrated multiple nodules or masses with high density in both lungs, and
      thickened interlobular septa. The 'halo sign' was observed around the high
      density lesions of the upper lobes. This range of CT images' characteristics is
      atypical, which differs from previous reports of this condition. 

PMID- 25590009
TI  - Rare and persistent Rhodococcus equi infection in a diffuse large B cell lymphoma
      patient: case report and review of the literature.
AB  - Rhodococcus equi (R. equi) is an uncommon gram positive organism. It is a rare
      but recognized pathogen in humans and has emerged as an important cause of
      morbidity and mortality among immunocompromised patients. Generally, R. equi
      infection needs combined treatment with effective antibiotics, and often requires
      the immune adjuvant therapy. Here we reported a 49-year-old man presented dyspnea
      with fever, skin ulcer for 5 months, and the final diagnosis was diffuse large B
      cell lymphoma with R. equi septicemia and pneumonia, the treatment was failure,
      the blood culture was always positive during the course of disease, though he was
      given combined treatment with effective antibiotics, perhaps the immune
      reconstitution or immune supportive treatment was more important. 

PMID- 25590011
TI  - The pure distal left main bronchial sleeve resection with total lung parenchymal
      preservation: report of two cases and literature review.
AB  - Pure bronchial sleeve resection and reconstruction is a type of rare thoracic
      surgery, especially for the second carina reconstruction on the left side, needs
      more exquisite surgical techniques, and patient selection to such surgery often
      requires rigorous screening. We present two cases of left main bronchial adenoid
      cystic carcinoma with the second carina reconstruction. The purpose of this paper
      is to recommend a useful supplement to conventional surgery for some very
      selected patients. 

PMID- 25590010
TI  - Good neurological recovery after rescue thrombolysis of presumed pulmonary
      embolism despite prior 100 minutes CPR.
AB  - We reported the case of a 70-year-old man who was admitted to neurologic wards
      for recurrent syncope for 3 years. Unfortunately, just 2 hours after his
      admission, he suddenly collapsed and failed to return of spontaneous circulation
      (ROSC) after a 100-minute standard cardiopulmonary resuscitation (CPR).
      Fortunately, he was timely suspected to have pulmonary embolism (PE) based on his
      sedentary lifestyle, elevated D-dimer and markedly enlarged right ventricle
      chamber on bedside echocardiography. After a rescue thrombolytic alteplase
      therapy, he was successfully resuscitated and good neurological recovery was
      achieved. 

PMID- 25590012
TI  - Pleural fluid is surrogate for time.

PMID- 25590013
TI  - 3-1-5 implementation for 2015.

PMID- 25590014
TI  - Panhellenic Congress News: innovation in the academic world.

PMID- 25590015
TI  - Keep calm in an emergency: an unexpected case with poisoning.

PMID- 25590016
TI  - Oxygen.

PMID- 25590017
TI  - Clinical Research Environment in India: Challenges and Proposed Solutions.
AB  - India has compelling need and keen aspirations for indigenous clinical research.
      Notwithstanding this need and previously reported growth the expected expansion
      of Indian clinical research has not materialized. We reviewed the scientific
      literature, lay press reports, and ClinicalTrials.gov data for information and
      commentary on projections, progress, and impediments associated with clinical
      trials in India. We also propose targeted solutions to identified challenges. The
      Indian clinical trial sector grew by (+) 20.3% CAGR (compound annual growth rate)
      between 2005 and 2010 and contracted by (-) 14.6% CAGR between 2010 and 2013.
      Phase-1 trials grew by (+) 43.5% CAGR from 2005-2013, phase-2 trials grew by (+)
      19.8% CAGR from 2005-2009 and contracted by (-) 12.6% CAGR from 2009-2013, and
      phase-3 trials grew by (+) 13.0% CAGR from 2005-2010 and contracted by (-) 28.8%
      CAGR from 2010-2013. This was associated with a slowing of the regulatory
      approval process, increased media coverage and activist engagement, and
      accelerated development of regulatory guidelines and recuperative initiatives. We
      propose the following as potential targets for restorative interventions:
      Regulatory overhaul (leadership and enforcement of regulations, resolution of
      ambiguity in regulations, staffing, training, guidelines, and ethical principles
      [e.g., compensation]).Education and training of research professionals,
      clinicians, and regulators.Public awareness and empowerment. After a peak in 2009
      2010, the clinical research sector in India appears to be experiencing a
      contraction. There are indications of challenges in regulatory enforcement of
      guidelines; training of clinical research professionals; and awareness,
      participation, partnership, and the general image amongst the non-professional
      media and public. Preventative and corrective principles and interventions are
      outlined with the goal of realizing the clinical research potential in India.

PMID- 25590018
TI  - Histoplasmosis Masquerading as a Rheumatoid Nodule in an Immunocompromised Host:
      A Case Report.

PMID- 25590019
TI  - Interprofessional and Interdisciplinary Approach from Undergraduate Health and
      Pre-Medical Students in Children's Health Educational Initiative.
AB  - The importance of interprofessional training in healthcare to improve quality of
      care and health outcomes has been increasingly recognized. This pilot study used
      an interprofessional and interdisciplinary team of undergraduate health and pre
      health students to establish a unique community partnership with a local
      elementary school in developing and implementing a nutrition/exercise educational
      intervention. Our results suggest that children as young as 8 years old are
      capable of learning new information related to the benefits of particular food
      groups, are capable of retaining this knowledge for 6 months, and that an
      intervention program as short as one hour every few months stand to make
      significant impact on children's knowledge about proper nutrition and healthy
      lifestyles. Our results suggest the potential benefits of further expanding the
      short-term intervention into a longer-term community-based curriculum targeting a
      younger age group previously or currently practiced.. Furthermore, this pilot
      study suggests that undergraduate health and pre-health students can form an
      interprofessional and collaborative team to take an active role in the
      dissemination of nutrition knowledge in the community.

PMID- 25590021
TI  - Comparing the Relationship Between Stature and Later Life Health in Six Low and
      Middle Income Countries.
AB  - This paper examines the relationship between stature and later life health in 6
      emerging economies, each of which are expected to experience significant
      increases in the mean age of their populations over the coming decades. Using
      data from the WHO Study on Global Ageing and Adult Health (SAGE) and pilot data
      from the Longitudinal Ageing Study in India (LASI), I show that various measures
      of health are associated with height, a commonly used proxy for childhood
      environment. In the pooled sample, an additional 10cm increase in height is
      associated with between a 2 and 3 percentage point increase in the probability of
      being in very good or good self-reported health, a 3 percentage point increase in
      the probability of reporting no difficulties with activities of daily living or
      instrumental activities of daily living, and between a fifth and a quarter of a
      standard deviation increase in grip strength and lung function. Adopting a
      methodology previously used in the research on inequality, I also summarise the
      height-grip strength gradient for each country using the concentration index, and
      provide a decomposition analysis.

PMID- 25590023
TI  - Comparison between antibiotic therapy of Brucellosis with and without vitamin A.
AB  - BACKGROUND: Brucellosis is one of the endemic diseases in our country and it can
      be in the types of acute, sub-acute or chronic. It estimates that about 20% of
      Brucellosis may change from acute to chronic. Because cell mediated immunity
      (CMI) is the main defense of body against Brucella species, it seems that some
      degree of Immunologic disorders existed in the patients with chronic form of
      diseases and some supplements such as Vitamin A (Vit A) as an immunomodulator can
      stimulate CMI and may decrease the rate of chronicity. MATERIALS AND METHODS: In
      a single-blind randomized clinical trial 120 patients with the clinical and
      serological diagnosed Brucellosis were randomized. A total of 60 patients
      received streptomycin and Doxycycline as standard therapy for 6 weeks and others
      in addition to this Regimen received Vit A for about 4 weeks. RESULTS: In the
      case group, only 1 case (1.6%) relapsed and in the control group 8 (13.5%) with
      significant difference (P < 0.005) between two groups. Morbidity of disease was
      different between two groups. CONCLUSION: Vit A therapy in the patients with
      Brucellosis with may reduce the disease morbidity and rate of chronicity.

PMID- 25590024
TI  - The Serum and salivary level of malondialdehyde, vitamins A, E, and C in patient
      with recurrent aphthous stomatitis.
AB  - BACKGROUND: Oral recurrent aphthous stomatitis (RAS) is a chronic inflammatory
      disease affected oral mucosa which has afflicted about 20% of the society.
      Etiology of this disease is unknown. Three main factors influencing aphthous
      stomatitis are genetic, hematologic, and immunologic factors. Another proposed
      factor that may be considered in etiology of aphthous ulcer is oxidant, anti
      oxidant imbalance in the body. The purpose of this study was the evaluation of
      lipid peroxide enzyme as an important oxidant agent and anti-oxidant vitamins in
      the saliva and serum of the patients suffering from RAS and compare it to healthy
      people. MATERIALS AND METHODS: In this cross-sectional, descriptive - analytical
      study, 25 patients suffering from RAS were compared to 24 healthy individuals.
      Applying enzyme-linked immunosorbent assay method, the amount of malondialdehyde
      (MDA) as well as Vitamins A, E, and C were measured in the saliva and serum of
      two groups. The results were analyzed by Statistical Package for the Social
      Sciences (SPSS) software version (11.5), t-test and chi(2). RESULTS: No
      significant difference was detected between salivary and serum levels of
      antioxidant vitamins (A, E, and C) and MDA in both experimental groups (P >
      0.05). CONCLUSION: According to the results of this study, RAS is not associated
      with oxidant-antioxidant imbalance in the body. However, it seems quite necessary
      to carry out more studies in this area.

PMID- 25590020
TI  - Overview and Historical Perspectives.
AB  - In this overview, we describe the history of Shiga toxin (Stx)-producing
      Escherichia coli (STEC) in two phases. In phase one, between 1977 and 2011, we
      learned that E. coli could produce Shiga toxin and cause both hemorrhagic colitis
      and the hemolytic-uremic syndrome in humans and that the prototype STEC-E. coli
      O157:H7-adheres to and effaces intestinal epithelial cells by a mechanism similar
      to that of enteropathogenic E. coli. We also recognized that the genes for Stx
      are typically encoded on a lysogenic phage; that STEC O157:H7 harbors a large
      pathogenicity island that encodes the elements needed for the characteristic
      attaching and effacing lesion; and that the most severe cases of human disease
      are linked to production of Stx type 2a, not Stx type 1a. Phase two began with a
      large food-borne outbreak of hemorrhagic colitis and hemolytic-uremic syndrome in
      Germany in 2011. That outbreak was caused by a novel strain consisting of
      enteroaggregative E. coli O104:H4 transduced by a Stx2a-converting phage. From
      this outbreak we learned that any E. coli strain that can adhere tightly to the
      human bowel (either by a biofilm-like mechanism as in E. coli O104:H4 or by an
      attaching and effacing mechanism as in E. coli O157:H7) can cause severe
      diarrheal and systemic illness when it acquires the capacity to produce Stx2a.
      This overview provides the basis for the review of current information regarding
      these fascinating and complex pathogens. 

PMID- 25590025
TI  - Immunocontraceptives: How far from reality?
AB  - Despite high expectations of safer, effective, economical, longer acting
      contraceptives, to date, there are no licensed contraceptive vaccines available
      in the market. Nevertheless, a role for vaccines undoubtedly exists as an aid to
      birth spacing and as a nonsurgical means of generating sterility. The research
      concerned in the area so far has been successful on the feline population, with
      room still for exhaustive studies on humans. The future of contraceptive vaccines
      holds great promise in terms of comfort, price, efficacy, rare complications, and
      possibly nonselective action on animal populations as well as on humans. This
      brief review deals with the basic aspects of immunocontraceptives along with the
      efforts done so far. There is a need for further research in aspects involving
      the rate of evolution of contraception resistance based on genetics, resistance
      phenotypes, or cross generation effects. Gonadotropin-releasing hormone and
      luteinizing-hormone have not been investigated in humans, as both reported
      impotency in animals; the follicle-stimulating hormone has been shown to cause
      oligospermia; zona pellucida has also not been studied in humans as it causes
      irreversible oophoritis, while the sperm has the potential for success in humans
      based on the data from immunoreproductive studies. Even as the position of the
      human chorionic gonadotropin vaccine looks hopeful, research on other possible
      targets continue with an eventual aim of discovering a vaccine that is more
      immunogenically effective. 

PMID- 25590022
TI  - Ocular drug delivery systems: An overview.
AB  - The major challenge faced by today's pharmacologist and formulation scientist is
      ocular drug delivery. Topical eye drop is the most convenient and patient
      compliant route of drug administration, especially for the treatment of anterior
      segment diseases. Delivery of drugs to the targeted ocular tissues is restricted
      by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug
      levels are not maintained for longer duration in target tissues. In the past two
      decades, ocular drug delivery research acceleratedly advanced towards developing
      a novel, safe and patient compliant formulation and drug delivery
      devices/techniques, which may surpass these barriers and maintain drug levels in
      tissues. Anterior segment drug delivery advances are witnessed by modulation of
      conventional topical solutions with permeation and viscosity enhancers. Also, it
      includes development of conventional topical formulations such as suspensions,
      emulsions and ointments. Various nanoformulations have also been introduced for
      anterior segment ocular drug delivery. On the other hand, for posterior ocular
      delivery, research has been immensely focused towards development of drug
      releasing devices and nanoformulations for treating chronic vitreoretinal
      diseases. These novel devices and/or formulations may help to surpass ocular
      barriers and associated side effects with conventional topical drops. Also, these
      novel devices and/or formulations are easy to formulate, no/negligibly
      irritating, possess high precorneal residence time, sustain the drug release, and
      enhance ocular bioavailability of therapeutics. An update of current research
      advancement in ocular drug delivery necessitates and helps drug delivery
      scientists to modulate their think process and develop novel and safe drug
      delivery strategies. Current review intends to summarize the existing
      conventional formulations for ocular delivery and their advancements followed by
      current nanotechnology based formulation developments. Also, recent developments
      with other ocular drug delivery strategies employing in situ gels, implants,
      contact lens and microneedles have been discussed.

PMID- 25590027
TI  - The frequency of agitation due to inappropriate use of naltrexone in addicts.
AB  - BACKGROUND: There is a high tendency among specialists to treat the addicts with
      naltrexone; withdrawal symptoms are frequent after taking naltrexone along with
      opioids. This study investigated the frequency of agitation due to inappropriate
      use of naltrexone in addicts. MATERIALS AND METHODS: This was a cross-sectional
      study, conducted in Noor and Aliasghar hospitals in Isfahan city. The study
      population included the addicts who were agitated as a result of naltrexone
      abuse. Scores of patients with agitation were measured with Richmond Agitation
      Sedation Scale (RASS). Patient outcomes including recovery without complications,
      recovery with complications (rhabdomyolysis), and mortality were recorded.
      RESULTS: All the patients with agitation caused by naltrexone abuse during 1 year
      were 40 people, of whom nine were excluded due to their comorbid diseases
      (diabetes or cardiovascular disease). Among the remaining 31 patients, 30 were
      male. The patients' mean age was 29.93 (5.24) years. The most common symptoms
      observed besides agitation was midriasis (41.9%), and vomiting (41.9%), A 38.8%
      of the patients scored 3 or 4, and, 61.2% scored 1 or 2 for agitation. The mean
      time for patients' restlessness scores to reach zero was 9.30 (3.71) h (min: 3 h,
      max: 18 h). All the patients in both groups were discharged with recovery without
      complication. CONCLUSION: Considering the high prevalence of agitation in the
      poisoning emergency department due to inappropriate use of naltrexone, more
      accurate planning for administration of naltrexone in addicts seems necessary.

PMID- 25590028
TI  - Preoperative evaluation of pelvic kidney renal cell carcinoma with 64-slice CT
      and 3D-CT angiography.
AB  - We report a case of a 55-year-old woman, who presented with a vague pelvic pain
      and was found to have an ectopic pelvic kidney involved by a mass. Preoperative
      assessment was done by multi-slice CT and 3D-CT angiography. According to our
      knowledge only eight cases of pelvic kidney tumor have been reported in the
      literature and our case is the first report of using multi-slice CT and 3D-CT
      angiography in the preoperative evaluation of these cases. 

PMID- 25590026
TI  - A comparison between standard triple therapy and sequential therapy on
      eradication of Helicobacter pylori in uremic patients: A randomized clinical
      trial.
AB  - BACKGROUND: The prevalence of peptic ulcer disease in hemodialysis dependent
      patients is higher than the general population. These patients are also more
      prone to upper gastrointestinal bleeding. The aim of this study was to compare
      the effects of a standard triple therapy with a sequential therapy on
      Helicobacter pylori eradication in azotemic and hemodialysis patients. MATERIALS
      AND METHODS: Forty nine hemodialysis and azotemic patients, naive to H. pylori
      treatment, were randomized into two groups to receive either standard triple
      therapy (pantoprazole 40 mg, amoxicillin 500 mg and clarithromycin 250 mg twice a
      day for 14 days) or a sequential therapy (pantoprazole 40 mg for 10 days,
      amoxicillin 500 mg twice a day for the first 5 days and clarithromycin 250 mg +
      tinidazole 500 mg twice a day just during the second 5 days). H. pylori
      eradication was evaluated by fecal H. pylori antigen assessment 8 weeks after the
      treatment. RESULTS: Of 49 patients, 45 patients (21 in triple therapy group and
      24 in the sequential group) completed the study. Based on intention to treat
      analysis, H. pylori eradication rates were 66.7% (95% confidence interval [CI]:
      47.8-85.5%) in standard triple therapy group and 84% (95% CI: 69.6-98.3%) in
      sequential therapy group (P = 0.34). Per-protocol (PP) eradication rates were
      (95% CI: 76.2%. 6-89.3%) 54 and 87.5% (95% CI: 68.8-95.5%), respectively (P =
      0.32). CONCLUSION: According to Maastricht III consensus report, the results of
      our study showed that sequential therapy might be a better choice compared with
      the standard triple therapy in azotemic and hemodialysis patients Iran. We
      propose to assess the effects of shorter-duration sequential therapy (less than
      10 days) for H. pylori eradication.

PMID- 25590029
TI  - Kefir protective effects against nicotine cessation-induced anxiety and cognition
      impairments in rats.
AB  - BACKGROUND: Nicotine as one of the potent psychostimulant drugs is characterized
      by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine
      intake, a number of symptoms such as anxiety, depression and cognition impairment
      develop. Kefir as a food supplement is rich in tryptophan. In this study, we have
      evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression
      and cognition impairment. MATERIALS AND METHODS: Forty adult male rats were
      divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17
      days and then the negative control groups got 5 mg/kg/day of normal saline. The
      positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The
      group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5
      mg/kg/day for 7 days. On the 25(th) day, Elevated Plus Maze (EPM), Open Field
      Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and
      depression. In addition, Moris Water Maze was applied to evaluate learning and
      memory in the animals between the 20(th) and 25(th) days. RESULTS: The results
      showed that administration of CMK, SMK and Sertraline had higher anti-depression
      and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in
      rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment
      results in the nicotine withdrawal period (P < 0.05). CONCLUSION: This study
      revealed that Kefir had a potential effect on the treatment of nicotine cessation
      induced depression, anxiety and cognition impairment in the animal model. Kefir
      may be useful for adjunct therapy for nicotine abandonment treatment protocols.

PMID- 25590030
TI  - Placement of long-term hemodialysis catheter (permcath) in patients with end
      stage renal disease through external jugular vein.
AB  - BACKGROUND: The number of patients with End-Stage Renal Disease (ESRD) has
      progressively increased in the population. Kidney transplantation is the specific
      treatment for such patients; however a majority of patients will require
      hemodialysis before kidney transplantation. The present study aims to investigate
      using the external jugular vein (EJV) for Permcath placement in these patients.
      MATERIALS AND METHODS: This descriptive and analytical study was conducted in
      Alzahra Medical Center, Isfahan, in 2012. Catheters were inserted by cutting down
      the right EJV. The patency rate and potential complications were studied. The
      obtained data was analyzed using SPSS 21.0. RESULTS: Out of 45 live patients,
      within three months of surgery, 40 patients (81.6%) had no complications and
      dialysis continued through Permcath. Permcath Thrombosis occurred in two patients
      (4.4%). Catheter infection led to the removal of it in one patient (2.2%) 1.5
      months after surgery. And accidental catheter removal occurred in one patient.
      CONCLUSION: Placement of the permcath in the external jugular vein can be a safe,
      uncomplicated, and reliable method for patients requiring hemodialysis, and can
      be a life-saving alternative in patients without accessible internal jugular
      vein.

PMID- 25590031
TI  - Comparing the treatment results of proximal humerus fracture based on surgical or
      nonsurgical methods.
AB  - BACKGROUND: A common type of Humerus fractures is about proximal. This study
      aimed to compare the results of surgical and non-surgical methods in treatment
      the Fracture of Proximal Humerus for decisions based on high-performance and less
      side effect. MATERIALS AND METHODS: This prospective clinical trial study was
      done on 114 patients 30-80 years old with proximal humerus fracture referred to
      the Isfahan hospital universities (Ayatollah Kashani and Al Zahra hospitals) in
      2007-2012. They were divided into two groups of 57 and treated surgically or non
      surgically. The self provided questionnaires were used to assess the consequences
      of the side effects. The patients returned for trial check up during 6 weeks, 3
      months, 6 months and one year after intervention. RESULT: In two parts fracture
      with displacement, nonsurgical treatment had lead to more complications rather
      than surgical treatment. In three-parts fracture non-union was seen in
      nonsurgical method in 6 weeks and in surgical method in 3, 6 months and one year
      after treatment, malunion was seen more in nonsurgical method rather than
      surgical method. In four-part fracture none-union results was seen more in
      nonsurgical method in 6 weeks, 3 months and one year and in surgical method in 6
      months after treatment, mal union was seen more in nonsurgical method rather than
      surgical method. CONCLUSION: The surgery in three and four parts fractures had
      fewer complications in the patients under 50 but not in the elders.

PMID- 25590032
TI  - Perspective on the hospital incidence rate of deep venous coagulopathy: Clinical
      and biochemical diagnostic markers.
AB  - BACKGROUND: Identifying factors contributing to the increased risk of deep venous
      thrombosis (DVT) in each population is vital, because of its life-threatening
      outcome. The current study aims to find the diagnostic performance of some
      laboratory coagulation markers for predicting DVT in an Iranian population
      complaining of DVT in the lower limbs. PATIENTS AND METHODS: For this study, 66
      consecutive patients with documented DVT, admitted to the Al-Zahra Hospital in
      Isfahan for the first time, were considered as the case group and 33 patients
      without DVT documentations were included as the control group. DVT was considered
      when there was visualization of thrombus or non-compressibility of the vein,
      confirmed by bilateral lower extremity compression Doppler ultrasonographic
      examination. Homocysteine, antiphospholipid, and anticardiolipin antibodies were
      measured in both groups by using sensitive ELISA kits. Protein C was measured via
      a functional clotting method, and prothrombin was measured by a kinetic,
      enzymatic assay. RESULTS: Multivariable analysis showed that the serum
      homocysteine levels was potentially associated with the presence of DVT after
      adjusting for age and gender (OR: 1.038, 95% CI: 1.007-1.070, P = 0.017).
      Comparison of the C statistic showed a partially good discrimination of
      homocysteine for DVT, with the area under the receiver operating characteristic
      (ROC) curve being 0.614 and with the optimal cut-off value of 16.5 micromol/L
      (MUmol/L) for men and 14.5 MUmol/L for women. CONCLUSION: Hyperhomocysteinemia
      could be considered as an independent risk factor for DVT, with an actual
      acceptable prognostic value, in the Iran population.

PMID- 25590033
TI  - Case report on the administration of an eighty milligram diazepam injection
      without respiratory depression.
AB  - Nowadays one of the most challenging problems in Medicine is addiction -
      addiction to sedative drugs such as benzodiazepines. In this article, we are
      going to describe a case of diazepam addiction that has tolerated a high dose of
      intravenous diazepam. 

PMID- 25590034
TI  - Comparison of Bristow procedure and Bankart arthroscopic method as the treatment
      of recurrent shoulder instability.
AB  - BACKGROUND: Anterior shoulder dislocation is the most common major joint
      dislocation. In patients with recurrent shoulder dislocation, surgical
      intervention is necessary. In this study, two methods of treatment, Bankart
      arthroscopic method and open Bristow procedure, were compared. MATERIALS AND
      METHODS: This clinical trial survey had been done in the orthopedic department of
      Alzahra and Kashani hospitals of Isfahan during 2008-2011. Patients with
      recurrent anterior shoulder dislocation who were candidates for surgical
      treatment were randomly divided into two groups, one treated by Bankart
      arthroscopic technique and the other treated by Bristow method. All the patients
      were assessed after the surgery using the criteria of ROWE, CONSTANT, UCLA, and
      ASES. Data were analyzed by SPSS software. RESULTS: Six patients (16.22%) had
      inappropriate condition with ROWE score (score less than 75); of them, one had
      been treated with Bristow and five with Bankart (5.26 vs. 27.78). Nine patients
      (24.32%) had appropriate condition, which included six from Bristow group and
      three treated by Bankart technique (31.58 vs. 16.67). Finally, 22 patients
      (59.46%) showed great improvement with this score, which included 12 from Bristow
      and 10 from Bankart groups (63.16 vs. 55.56). According to Fisher's exact test,
      there were no significant differences between the two groups (P = 0.15).
      CONCLUSION: The two mentioned techniques did not differ significantly, although
      some parameters such as level of performance, pain intensity, use of analgesics,
      and range of internal rotation showed more improvement in Bristow procedure.
      Therefore, if there is no contraindication for Bristow procedure, it is preferred
      to use this method.

PMID- 25590035
TI  - Comparison of the effects of two different formulas of fluids in craniotomy
      patients.
AB  - BACKGROUND: Intraoperative fluid management of the patients who had undergone
      neurosurgery presents special challenges for the anesthesiologist. In this study,
      we aimed to compare the effects of two fluid combinations (half-normal +
      bicarbonate with saline + Ringer's lactate) on brain relaxation, and acid, base,
      and hemodynamic balance in patients undergoing elective craniotomy surgery.
      MATERIALS AND METHODS: This randomized double-blind controlled clinical trial
      study was done on 50 patients, of age 20-60 years, undergoing craniotomy in
      Alzahra Hospital in 2012. They were divided in two groups of 25 patients each. In
      the control group, after the patients received hypertonic saline, normal saline
      serum and Ringer's lactate was administered, and in the half-normal study group,
      80 ml of sodium bicarbonate for every liter of it was added. Arterial blood gas
      (ABG) was taken before the last suture. Brain relaxation before dura opening was
      registered. RESULTS: There was no significant difference in heart rate changes (P
      = 0.054). No significant difference was observed in the mean arterial pressure
      between the two groups (P = 0.99). Changes in pH, HCO3, and BE were not
      significantly different (P = 0.99) between the two groups. Urine output in half
      normal saline group was significantly higher than in normal saline group. The
      mean bleeding volume was higher in normal saline group, but was not significantly
      different (P = 0.54). The mean volume of injected blood was higher in half-normal
      group with a significant difference (P = 0.54). The injected blood volume mean in
      half-normal group was higher with no significant difference (P = 0.55). The mean
      of brain relaxation was not different (P = 0.5). CONCLUSION: These two fluids did
      not show any significant differences in the studied variables in this research.

PMID- 25590036
TI  - From Measurement to Analysis Reporting: Grand Challenges in Nutritional
      Methodology.

PMID- 25590038
TI  - Biogenic amine metabolism in juvenile neurocardiogenic syncope with dysautonomia.
AB  - OBJECTIVE: Biogenic amine brain levels and their cerebral metabolism are
      frequently studied by quantitation of biogenic amine metabolites in cerebrospinal
      fluid (CSF) compared to age-matched controls. There is a paucity of studies in
      adolescents and young adults investigating the potential role of disordered
      cerebral biogenic amine metabolism in young patients who have dysautonomia based
      on abnormal head-up tilt table (HUTT). METHODS: In a cohort of juvenile patients
      with neurocardiogenic syncope and dysautonomia documented by abnormal HUTT,
      biogenic amine metabolites of dopamine and serotonin were quantitated in 18
      patients (15 females). HUTT testing is an effective clinical method to evaluate
      posturally induced physiological events in patients suspected of neurocardiogenic
      syncope with dysautonomia. RESULTS: Levels of the dopamine metabolite
      (homovanillic acid: HVA) and/or the serotonin metabolite (5-hydroxyindoleacetic
      acid: 5HIAA) were significantly reduced in 13 patients compared to age-matched
      controls. INTERPRETATION: Peripheral biogenic amines and their metabolites have
      been extensively studied in adults with dysautonomia due to various
      neurodegenerative disorders (Parkinson disease, multiple system atrophy, primary
      autonomic failure). Our findings indicate that more than two-thirds of this
      cohort of young patients with dysautonomia of variable severity have a defect in
      cerebral biogenic amines, particularly in dopamine and serotonin metabolism.

PMID- 25590037
TI  - Identification of Srp9 as a febrile seizure susceptibility gene.
AB  - OBJECTIVE: Febrile seizures (FS) are the most common seizure type in young
      children. Complex FS are a risk factor for mesial temporal lobe epilepsy (mTLE).
      To identify new FS susceptibility genes we used a forward genetic strategy in
      mice and subsequently analyzed candidate genes in humans. METHODS: We mapped a
      quantitative trait locus (QTL1) for hyperthermia-induced FS on mouse chromosome
      1, containing the signal recognition particle 9 (Srp9) gene. Effects of
      differential Srp9 expression were assessed in vivo and in vitro. Hippocampal SRP9
      expression and genetic association were analyzed in FS and mTLE patients.
      RESULTS: Srp9 was differentially expressed between parental strains C57BL/6J and
      A/J. Chromosome substitution strain 1 (CSS1) mice exhibited lower FS
      susceptibility and Srp9 expression than C57BL/6J mice. In vivo knockdown of brain
      Srp9 reduced FS susceptibility. Mice with reduced Srp9 expression and FS
      susceptibility, exhibited reduced hippocampal AMPA and NMDA currents.
      Downregulation of neuronal Srp9 reduced surface expression of AMPA receptor
      subunit GluA1. mTLE patients with antecedent FS had higher SRP9 expression than
      patients without. SRP9 promoter SNP rs12403575(G/A) was genetically associated
      with FS and mTLE. INTERPRETATION: Our findings identify SRP9 as a novel FS
      susceptibility gene and indicate that SRP9 conveys its effects through
      endoplasmic reticulum (ER)-dependent synthesis and trafficking of membrane
      proteins, such as glutamate receptors. Discovery of this new FS gene and
      mechanism may provide new leads for early diagnosis and treatment of children
      with complex FS at risk for mTLE.

PMID- 25590040
TI  - Contribution of non-reference alleles in mtDNA of Alzheimer's disease patients.
AB  - Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be
      responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here
      we examined the signal intensity of the four alleles of each mtDNA nucleotide
      position (np) in whole blood of AD patients and age-matched controls using
      MitoChip v2.0 array. Our analysis identified 270 significantly different nps
      which, with one exception, showed an increased contribution of non-reference
      alleles in AD patients. Principal component analysis (PCA) and cluster analysis
      showed that five of these nps could discriminate AD from control subjects with
      80% of cases correctly classified. Our data support the hypothesis of mtDNA
      alterations as an important factor in the etiology of AD. 

PMID- 25590039
TI  - Heterogeneity of oligodendrocyte progenitor cells in adult human brain.
AB  - OBJECTIVE: Remyelination in multiple sclerosis has been attributed to the
      presence of oligodendrocyte progenitor cells (OPCs) in brain parenchyma. However,
      the precise identity of these progenitors is poorly defined. Here, we
      characterized populations of OPCs in the adult human brain and examined their
      myelination capacity and profile of miRNAs. Comparisons were made with fetal OPCs
      and mature oligodendrocytes. METHODS: We isolated human adult and fetal (early-to
      mid second trimester) OPCs from surgically resected brain tissues using O4-, A2B5
      , and MOG-directed fluorescence activated cell sorting and transplanted them into
      dysmyelinated shiverer slices to examine their myelination capacity. We used qRT
      PCR to analyze expression of selective miRNAs implicated in OPC biology. RESULTS:
      Three subsets of putative OPCs were identified in adult brains: (1) A2B5(+), (2)
      O4(low), and (3) A2B5(+)O4(high)MOG(+) progenitors. In comparison, fetal brains
      contained (1) A2B5(+), (2) O4(+), and (3) A2B5(+)O4(+) progenitors, but no MOG(+)
      cells. We demonstrate that like fetal OPCs, adult OPCs have the capacity to
      ensheathe cerebellar axons. However, adult OPCs exhibit low to undetectable
      expression of miRNAs that were highly expressed in O4-expressing fetal OPCs.
      Adult OPCs also express different miRNAs compared to mature oligodendrocytes.
      INTERPRETATION: We conclude that phenotypically distinct subsets of OPCs are
      present in adult human brain and these OPCs show differential miRNA expression
      compared to fetal OPCs and mature oligodendrocytes. These suggest that
      remyelination in adult brain may involve multiple populations of progenitors
      within the brain and that OPC differentiation in adulthood may be differentially
      regulated compared to development.

PMID- 25590042
TI  - Discharge responses of the optic tract to flash stimuli in Parkinson's disease.
AB  - Dopamine has a significant role in retinal processing, and it has been
      demonstrated that retinal dopamine content is decreased in parkinsonian patients.
      We measured the latency of the evoked discharges in the optic tract (OT) to flash
      stimuli during stereotactic pallidal neurosurgery in 25 patients with Parkinson's
      disease (PD) (13 women and 12 men, age 38-78 years, unified Parkinson's disease
      rating scale (UPDRS) Motor Score in the Off state 11-54, Hoehn and Yahr stage in
      the Off state 1.5-5) and investigated the effects of age at surgery, disease
      duration, levodopa dose, and severity of parkinsonian symptoms on the latency. OT
      discharges were evoked by monocular flash stimuli delivered from a flashlight
      with a krypton bulb with a tungsten filament. The luminance at the eye measured
      ~4 * 10(4) cd/m(2). The light wavelength of the stimulus was composed of a wide
      spectrum with its peak at around 800 nm or longer. The latency of OT discharges
      ranged 49-79 msec, and there was a significant positive correlation between the
      latencies of evoked activities in the OT to a flashlight and age (r = 0.59, P <
      0.001, by Pearson correlation), but no correlation between the latency and the
      severity of parkinsonian symptoms and between the latency and duration of
      illness. These results indicate that the delay in visual processing and
      conduction at the level of the retina and the OT are substantially derived from
      age-related degenerative changes in the retina and visual pathway which are
      apparently unrelated to the striatal dopamine deficiency in PD. 

PMID- 25590041
TI  - Subtle retinal pathology in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by neuro-ophthalmological
      abnormalities beyond disturbed oculomotor control such as decreased visual acuity
      and disturbed visual evoked potentials. Here we report retinal alterations in a
      cohort of 24 patients with clinically definite (n = 20) or probable (n = 4) ALS
      as compared to matched controls. High-resolution spectral domain optical
      coherence tomography with retinal segmentation revealed a subtle reduction in the
      macular thickness and the retinal nerve fiber layer (RNFL) as well as a marked
      thinning of the inner nuclear layer (INL). Our data indicate an unprecedented
      retinal damage pattern and suggest neurodegeneration beyond the motor system in
      this disease. 

PMID- 25590043
TI  - Spinal cord atrophy in early Huntington's disease.
AB  - Despite evidence for spinal cord involvement, it remains unclear whether spinal
      cord atrophy exists in early Huntington's disease. We studied magnetic resonance
      images, covering both brain and upper cervical cord, in two cohorts of
      Huntington's patients and in one cohort of Alzheimer's patients. All cohorts
      included healthy controls comparable with regard to age and gender. We found
      significant spinal cord atrophy in both cohorts of Huntington's patients but not
      in the cohort of Alzheimer's patients. Furthermore, spinal cord atrophy
      correlated with motor symptoms indicating that spinal cord atrophy occurs in the
      clinical stages and does not result from abnormal development. 

PMID- 25590046
TI  - Head accelerometry may be useful as a test of psychogenic head tremor.

PMID- 25590045
TI  - Beta-2-Adrenergic Receptor Methylation Influences Asthma Phenotype in The School
      Inner City Asthma Study.
AB  - Asthma is the most common chronic illness of childhood and inner city residents
      suffer a disproportionately high rate of asthma diagnosis and asthma morbidity.
      The School Inner City Asthma Study investigates the school classroom based
      environmental exposures that may lead to asthma morbidity in inner city school
      children with asthma. Within this cohort, we investigated the role of methylation
      at the promoter region of the beta-2-adrenergic receptor in relation to asthma
      morbidity. We found that high levels of methylation in the region studied was
      significantly associated with decreased report of dyspnea and trended towards
      significance for lower levels of asthma symptoms and airway obstruction. This
      Research Highlight discusses the findings of the recent study and the
      investigators' active research endeavors.

PMID- 25590047
TI  - Biodemographic Analyses of Longitudinal Data on Aging, Health, and Longevity:
      Recent Advances and Future Perspectives.
AB  - Biodemography became one of the most innovative and fastest growing areas in
      demography. This progress is fueled by the growing variability and amount of
      relevant data available for analyses as well as by methodological developments
      allowing for addressing new research questions using new approaches that can
      better utilize the potential of these data. In this review paper, we summarize
      recent methodological advances in biodemography and their diverse practical
      applications. Three major topics are covered: (1) computational approaches to
      reconstruction of age patterns of incidence of geriatric diseases and other
      characteristics such as recovery rates at the population level using Medicare
      claims data; (2) methodological advances in genetic and genomic biodemography and
      applications to research on genetic determinants of longevity and health; and (3)
      biodemographic models for joint analyses of time-to-event data and longitudinal
      measurements of biomarkers collected in longitudinal studies on aging. We discuss
      how such data and methodology can be used in a comprehensive prediction model for
      joint analyses of incomplete datasets that take into account the wide spectrum of
      factors affecting health and mortality transitions including genetic factors and
      hidden mechanisms of aging-related changes in physiological variables in their
      dynamic connection with health and survival.

PMID- 25590048
TI  - Astrocyte mediated MMP-9 activation in the synapse dysfunction: An implication in
      Alzheimer disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that occurs
      due to spasms of the neurons, resulting in loss of memory and behavioral changes.
      In particular, synaptic loss has been described as an early event in the
      pathogenesis of AD. The increasing evidences have suggested the role of many
      matrix metalloproteinase (MMPs) in central nervous system (CNS) pathology. Many
      studies showed that MMPs enzymes are important for the pathophysiological process
      during Alzheimer's disease (AD). It is usually believed that the synaptic
      dysfunction and synapse loss contribute to the cognitive deficits of patients
      with AD. Cerebrovascular events such as blood-brain barrier (BBB) disruption lead
      to neuronal damage as well as neuroinflammation. BBB dysfunctions are observed at
      an early post injury time point, and are associated with activation of proteases,
      such as MMPs especially MMP-9 which is actively engage in a neuronal injury in
      the most of the neurodegenerative disorders. BBB opening is accompanied by
      astrocytic activation, BBB injury and dysregulation of cerebral blood flow.
      Activated MMPs disrupt neurovascular unit (NVU) which may starve the neurons and
      affect the synapse function by altering synaptic plasticity and ultimately lead
      to cognitive decline. However, how MMPs implicated in synaptic dysfunction what
      are the mechanism associated with this disparity needs to discuss for better
      understanding the role of MMP-9 in pathogenesis of AD. In this review, we focused
      on the role of astrocytes and MMP-9 in synaptic dysfunction. We also, underlined
      possible pharmacological strategies for drug development that might offer more
      insight into the pathogenesis of cerebrovascular disease such as stroke and
      Vascular dementia.

PMID- 25590049
TI  - Pre-Clinical Models of Acquired Neonatal Seizures: Differential Effects of Injury
      on Function of Chloride Co-Transporters.
AB  - Hypoxic-ischemic encephalopathy [HIE] represents the most common acquired
      pathology associated with neonatal seizures. HIE-associated neonatal seizures are
      often difficult to control, due to their refractoriness to traditional anti
      seizure agents. Developmentally regulated chloride gradients during early
      development make the neonatal brain more seizure-susceptible by depolarizing
      GABAAR-mediated currents, and therefore hindering inhibition by conventional anti
      seizure drugs such as phenobarbital [PB] and benzodiazepines. Pharmaco-modulation
      of chloride co-transporters has become a current field of research in treating
      refractory neonatal seizures, and the basis of two clinical trials [NCT01434225;
      NCT00380531]. However, the recent termination of NEMO study [NCT01434225] on
      bumetanide, an NKCC1 antagonist, suggests that clinical utilization of bumetanide
      as an adjunct to treat neonatal seizures with PB may not be a viable option.
      Hence, re-evaluation of bumetanide as an adjunct through pre-clinical studies is
      warranted. Additionally, the model-specific variability in the efficacy of
      bumetanide in the pre-clinical models of neonatal seizures highlights the
      differential consequences of insults used to induce seizures in each pre-clinical
      model as worth exploration. Injury itself can significantly alter the function of
      chloride co-transporters, and therefore the efficacy of anti-seizure agents that
      follow.

PMID- 25590051
TI  - Degradation of two fluoroquinolone antibiotics photoinduced by Fe(III)-microalgae
      suspension in an aqueous solution.
AB  - The widespread presence of fluoroquinolone antibiotics (FQs) in natural
      ecosystems is a health hazard for humans and other living organisms. In this
      work, the photochemical degradation process of two antibiotics in the presence of
      Fe(III) and marine microalgae has been studied. Two fluoroquinolone (FQ)
      antibiotics, enrofloxacin (ENR) and ciprofloxacin hydrochloride (CIP), and two
      marine microalgae, Platymonas subcordiformis and Isochrysis galbana, were
      investigated under irradiation with a high-pressure mercury lamp (HPML) in a
      laboratory-scale experiment. The effects of the initial concentration of
      antibiotics on the degradation of these two FQs in Fe(III)-algae suspensions were
      also investigated. On the basis of the information in this study, compared to
      other systems, the efficiency of photo-degradation of the two FQs is better at
      lower FQ concentrations in the Fe(III)-algae system. Moreover, the low initial
      concentration of antibiotics benefits the photochemical process of antibiotics.
      This work demonstrated that the Fe(III)-algae system is an interesting and
      valuable research area and could be considered as a promising photochemical
      system for seawater remediation.

PMID- 25590053
TI  - Proceedings of the 11th Annual MCBIOS Conference, March 6-8, 2014, Stillwater,
      Oklahoma.

PMID- 25590050
TI  - Replication of SCN5A Associations with Electrocardio-graphic Traits in African
      Americans from Clinical and Epidemiologic Studies.
AB  - The NAv1.5 sodium channel alpha subunit is the predominant alpha-subunit
      expressed in the heart and is associated with cardiac arrhythmias. We tested five
      previously identified SCN5A variants (rs7374138, rs7637849, rs7637849, rs7629265,
      and rs11129796) for an association with PR interval and QRS duration in two
      unique study populations: the Third National Health and Nutrition Examination
      Survey (NHANES III, n= 552) accessed by the Epidemiologic Architecture for Genes
      Linked to Environment (EAGLE) and a combined dataset (n= 455) from two biobanks
      linked to electronic medical records from Vanderbilt University (BioVU) and
      Northwestern University (NUgene) as part of the electronic Medical Records &
      Genomics (eMERGE) network. A meta-analysis including all three study populations
      (n~4,000) suggests that eight SCN5A associations were significant for both QRS
      duration and PR interval (p<5.0E-3) with little evidence for heterogeneity across
      the study populations. These results suggest that published SCN5A associations
      replicate across different study designs in a meta-analysis and represent an
      important first step in utility of multiple study designs for genetic studies and
      the identification/characterization of genetic variants associated with ECG
      traits in African-descent populations.

PMID- 25590054
TI  - Proceedings of the the 5th Symposium on Antimicrobial Resistance in Animals and
      the Environment (ARAE 2013), June 30-July 3, 2013, Ghent, Belgium.

PMID- 25590052
TI  - Proceedings of the 13th European Conference on Computational Biology (ECCB'14),
      September 7-10, 2014, Strasbourg, France.

PMID- 25590056
TI  - European Society of Cardiology European  Affairs: bringing science to policy
      makers.

PMID- 25590055
TI  - Efficacy and safety of human placental extract for alcoholic and nonalcoholic
      steatohepatitis: an open-label, randomized, comparative study.
AB  - Human placental extract (HPE) is a traditional medicine that has been used for
      the symptomatic treatment of liver disease without any verifying clinical
      evidence. This study aimed to evaluate the efficacy and safety of HPE in patients
      with alcoholic or nonalcoholic steatohepatitis (ASH or NASH). We designed this
      clinical trial as a multicenter, open-label, randomized, comparative
      noninferiority study to improve the reliability of analyses. The enrollment
      criteria were limited to ASH or NASH patients with serum alanine aminotransferase
      (ALT) 1.5-fold higher than the normal level. Patients in the control group were
      treated with a commercially available mixture of liver extract and flavin adenine
      dinucleotide (LE-FAD). Intention-to-treat (ITT) analysis was applied to 194
      patients, and per-protocol (PP) analysis was available for 154 patients. The rate
      of primary goal achievement of treatment efficacy was arbitrarily defined as 20%
      or greater improvement in ALT level compared with the pretreatment level and did
      not differ significantly between the HPE and control groups [62.9% (44/70) vs.
      48.8% (41/84); p=0.0772]. ITT and modified ITT analysis showed results similar to
      those of PP analysis. Adverse drug reactions (ADRs) of minimal to moderate degree
      occurred in 3.1% of patients. The ADR and treatment compliance rates were similar
      in both groups. In conclusion, the clinical value of HPE in the treatment of ASH
      and NASH is equivalent to that of LE-FAD.

PMID- 25590057
TI  - Taskforce QRS.

PMID- 25590059
TI  - The pinch patch technique.

PMID- 25590058
TI  - Influence of serum albumin levels during opioid rotation from morphine or
      oxycodone to fentanyl for cancer pain.
AB  - Morphine, oxycodone, and fentanyl are commonly used to control cancer pain.
      Because these drugs have differences in receptor affinity or pharmacokinetic
      parameters, changing the opioid formulation may result in an unexpected outcome,
      depending on the patient's condition. This study investigated whether low serum
      protein levels influence the effectiveness of opioid rotation by determining the
      impact of serum albumin levels on the analgesic effect before and after opioid
      rotation from morphine or oxycodone to fentanyl in cancer patients. The patients
      were classified into 3 groups according to their serum albumin levels before
      opioid rotation: group 1, <2.5 g/dL; group 2, from 2.5 g/dL to <3.0 g/dL; and
      group 3, >=3.0 g/dL. There was no significant change in the percentage of
      patients with good pain control after rotation in group 1 or group 2; however,
      the percentage of patients with good pain control increased significantly in
      group 3. When the percentage of patients whose numerical rating scale scores
      increased, were unchanged, or decreased after rotation were compared, a
      significant difference in the percentage of those showing improvement was noted
      among the 3 groups and between groups 1 and 3. These findings suggest that
      monitoring serum albumin levels during fentanyl therapy is useful for pain
      management, and that the effectiveness of opioid rotation to fentanyl in patients
      with serum albumin levels of <2.5 g/dL should be carefully evaluated after
      rotation.

PMID- 25590060
TI  - Novel use of the retinoscope in visualization of the anterior segment.

PMID- 25590061
TI  - In Memoriam: Hans von Leden.

PMID- 25590062
TI  - Proceedings of The 8th World Congress on Vaccines, Immunisation and
      Immunotherapy, June 5-7, 2012, Barcelona, Spain.

PMID- 25590065
TI  - Rating the planet's oceans.

PMID- 25590063
TI  - Proceedings of the Fifth International Brain-Computer Interface Meeting, June 3
      7, 2013, Pacific Grove, CA.

PMID- 25590066
TI  - Using bacteria to reduce impact of diazepam in UK rivers.

PMID- 25590067
TI  - Nanoparticles accumulate quickly in wetland sediment.

PMID- 25590068
TI  - Pollution linked to lethal sea turtle tumours.

PMID- 25590069
TI  - Coral's best defender against an army of sea stars.

PMID- 25590070
TI  - Proceedings and abstracts of the 29th International Workshop on Surfactant
      Replacement, May 30-31, 2014, Valencia, Spain.

PMID- 25590071
TI  - Whaling commission shifts toward conservation agenda.

PMID- 25590072
TI  - Recreational activity a major pollutant on Canadian Pacific  coast.

PMID- 25590073
TI  - Changing Antarctic waters could trigger steep rise in sea levels.

PMID- 25590074
TI  - Big changes in the Sargasso Sea.

PMID- 25590075
TI  - Microplastic pollution discovered in St. Lawrence River  sediments.

PMID- 25590077
TI  - Changes in coastal upwelling linked to temporary declines in  marine ecosystem.

PMID- 25590076
TI  - Tropical fish a threat to Mediterranean Sea ecosystems.

PMID- 25590079
TI  - Proceedings of the 6th ANIRCEF National Congress - Headache and Social Context,
      29-31 May, 2014, Asti, Italy.

PMID- 25590081
TI  - Oncology scan--primary central nervous system lymphoma.

PMID- 25590083
TI  - The challenges faced by the Korean Society for Radiation Oncology in the national
      healthcare system in Korea.

PMID- 25590084
TI  - Puerarin enhances bone mass by promoting osteoblastogenesis and slightly lowering
      bone marrow adiposity in ovariectomized rats.
AB  - We investigated the effect of puerarin on bone mass and marrow adiposity in
      ovariectomy (OVX)- induced osteoporosis. The rats were divided into four groups:
      control; OVX; OVX+estradiol (OVX-E); and OVX+puerarin treatment (OVX-GE). In
      vivo, bone mineral density (BMD) and histomorphometry were measured under
      microCT. The mechanical properties of tibia were obtained in 3-point bending
      test. Plasma osteocalcin and adiponectin were determined using enzyme-linked
      immunosorbent assay (ELISA). Alkaline phosphatase (ALP) were measured using
      biochemical methods. In vitro, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) and Oil Red O staining were used to compare
      osteoblast proliferation and adipocyte differentiation, respectively. Osteocalcin
      and adiponectin in culture supernatants were determined using ELISA. The results
      showed that puerarin significantly enhanced bone volume density and trabecular
      number compared with OVX and OVX-E groups (p<0.05, p<0.05, respectively).
      Puerarin increased energy to ultimate load, plasma osteocalcin and ALP (p<0.01).
      However, BMD in OVX-GE group was less than that in control (p<0.01) and OVX-E
      groups (p<0.05). The culture supernatants from OVX-GE group showed increased
      osteocalcin compared with those from OVX (p<0.01) and OVX-E groups (p<0.05).
      Puerarin lowered adiponectin in culture supernatant compared with supernatant
      from OVX group and inhibited the increase in adipocytes caused by OVX (p<0.01).
      However, the amount of lipids did not differ between OVX-GE and OVX groups. These
      findings suggest that puerarin likely enhances bone formation by stimulating the
      proliferation and differentiation of osteoblasts while slightly inhibiting the
      adipotic differentiation.

PMID- 25590086
TI  - Role of simplex lattice statistical design in the formulation and optimization of
      microemulsions for transdermal delivery.
AB  - Microemulsions (ME) have gained attention as an alternative pharmaceutical
      formulation for transdermal delivery systems. However, the complicated
      relationships between various ME compositions (causal factors) and their
      characteristics (response variable) have not been fully comprehended. To overcome
      this problem, the design and development of ME for transdermal delivery was
      performed in our study using Design Expert((r)) Software. The model formulations
      of ME were prepared according to the ME region obtained from pseudo-ternary phase
      diagrams using the simplex lattice design as an optimization technique. In this
      study, ketoprofen-loaded ME composed of oleic acid, Cremophor((r)) RH40, ethanol
      and water were prepared, and their characteristics (e.g., size, charge,
      conductivity, pH, viscosity, drug content, loading capacity and skin permeation
      flux) were evaluated. The ME having an appropriate skin permeation flux was used
      as the basis for optimization. The skin permeation flux of the experimental ME
      was very close to the flux predicted by Design Expert((r)) Software and was
      significantly greater than that for the commercial product. Possible mechanisms
      for the enhancement of the skin permeation of the ME were also investigated using
      Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD). This
      finding provided an understanding of the relationship between the causal factors
      and response variables, as shown in the response surfaces. Moreover, these
      results indicated that the simple lattice design was beneficial for the
      pharmaceutical development of ME for transdermal delivery.

PMID- 25590089
TI  - Nephrotoxicity induced by piperacillin-tazobactam in late elderly Japanese
      patients with nursing and healthcare associated pneumonia.
AB  - This study aimed to clarify the efficacy, safety, and pharmacokinetics of
      piperacillin-tazobactam (PIPC- TAZ) in late elderly Japanese patients. This is
      the first antimicrobial pilot study in late elderly patients with nursing and
      healthcare associated pneumonia. After PIPC-TAZ administration, PIPC
      concentrations in plasma were measured chromatographically and the
      pharmacokinetic parameters were estimated. Efficacy, safety, and bacteriological
      evaluations were also carried out. The mean age was 85.0 years old and most of
      the patients were late elderly. Chest X-rays, body temperature, white blood cell
      count, and C reactive protein all improved significantly, and a high efficacy
      ratio of 90.9% was observed. Serious nephrotoxicity was observed in 4 cases
      (18.2%) after administration of PIPC-TAZ. Creatinine clearance (meanS.D.)
      measured before PIPC-TAZ therapy was significantly lower in the nephrotoxicity
      group (32.54.4 mL/min) than in the non-nephrotoxicity group (46.116.7 mL/min),
      although the ages were not different between the 2 groups. In the pharmacokinetic
      parameters for PIPC, total clearance was slightly lower in the nephrotoxicity
      group than in the non-nephrotoxicity group. However, no significant difference
      was observed in plasma PIPC levels between the 2 groups. In patients with renal
      impairment, especially with a creatinine clearance of <40 mL/ min, renal
      impairment was found to be an influencing factor for severe nephrotoxicity
      following PIPC-TAZ administration. In conclusion, the results suggest that
      physicians should pay close attention in order to avoid possible toxicity, and
      that deliberate administration planning and careful follow-up are required in
      late elderly patients with comprised organ dysfunction.

PMID- 25590090
TI  - Renin inhibition improves ovariectomy-induced osteoporosis of lumbar vertebra in
      mice.
AB  - The skeletal renin-angiotensin system (RAS) is involved in the progression of
      osteoporosis and the active peptide within the RAS, angiotensin II (ANG II), has
      deleterious effects on bones. This study was performed to investigate whether
      suppression of the rate-limiting step of the RAS cascade by the renin inhibitor
      aliskiren has a benefit on trabecular bone in osteoporotic mice. A postmenopausal
      osteoporosis model was induced by bilateral ovariectomy. The ovariectomized (OVX)
      mice were treated with a low (5 mg/kg) or high (25 mg/kg) dose of aliskiren for 6
      weeks. Micro-computed tomography was performed to detect trabecular bone
      parameters of lumbar vertebra and to obtain 3-dimensional (3D) images. Treatment
      with aliskiren markedly increased bone volume over total volume (p<0.05),
      trabecular bone number (p<0.05), connectivity density (p<0.05), and bone mineral
      density (p<0.05) and reduced trabecular bone separation (p<0.05) compared to
      vehicle-treated OVX mice. Similarly, the 3D images were consistent with the
      quantitative data that showed aliskiren could markedly reverse the ovariectomy
      induced pathological changes of trabecular bone. Thus, this study indicated that
      the treatment of estrogen-deficient mice with aliskiren could markedly increase
      bone mass and improve trabecular bone structure, suggesting its potential
      application in treating postmenopausal osteoporosis.

PMID- 25590091
TI  - [Does prolonged ceftaroline therapy frequently cause neutropenia?].

PMID- 25590092
TI  - Preface. Insoluble proteins.

PMID- 25590102
TI  - Proceedings of the 7th Copenhagen Workshop on Endocrine Disrupters, 28-31 May,
      2013,Copenhagen, Denmark.

PMID- 25590096
TI  - State trends in the cost of employer health insurance coverage, 2003-2013.
AB  - From 2010 to 2013--the years following the implementation of the Affordable Care
      Act--there has been a marked slowdown in premium growth in 31 states and the
      District of Columbia. Yet, the costs employees and their families pay out-of
      pocket for deductibles and their share of premiums continued to rise, consuming a
      greater share of incomes across the country. In all but a handful of states,
      average deductibles more than doubled over the past decade for employees working
      in large and small firms. Workers are paying more but getting less protective
      benefits. Costs are particularly high, compared with median income, in Southern
      and South Central states, where incomes are below the national average. Based on
      recent forecasts that predict an uptick in private insurance growth rates
      starting in 2015, securing slow cost growth for workers, families, and employers
      will likely require action to address rising costs of medical care services.

PMID- 25590103
TI  - Homage to Professor Jean-Michel Thomine.

PMID- 25590104
TI  - Jean-Michel Thomine has left us.

PMID- 25590128
TI  - Perfluoroalkyl acids and their precursors in Swedish food: The relative
      importance of direct and indirect dietary exposure.
AB  - We analyzed food market basket samples obtained in Sweden from 1999, 2005, and
      2010 for perfluoroalkyl acids (PFAAs) and a range of precursor compounds.
      Perfluorooctane sulfonic acid (PFOS) precursors were detected in all food year
      pools with the highest concentrations in 1999. Six polyfluoroalkyl phosphate
      diesters (diPAPs, 4:2/6:2, 6:2/6:2, 6:2/8:2, 8:2/8:2, 6:2/10:2, and 10:2/10:2)
      were detected in the year pools with the highest ?diPAP concentrations in 1999
      and 2005. All precursors were predominantly found in meat, fish, and/or eggs
      based on analysis of individual food groups from 1999. Based on year pools, PFOS
      precursors contributed between 4 and 1% as an indirect source to total dietary
      PFOS intakes between 1999 and 2010. Perfluorohexanoic acid (PFHxA) exposure
      originated entirely from diPAPs, whereas for perfluorooctanoic acid (PFOA) and
      perfluorodecanoic acid (PFDA), diPAPs contributed between 1 and 19% to total
      exposure. The lowest precursor contributions were generally seen in food samples
      from 2010. 

PMID- 25590129
TI  - Chemical composition of vegetation along urbanisation gradients in two European
      cities.
AB  - Accumulation of particulate matter (PM) and metals on leaves of three deciduous
      woody species was studied along urbanisation gradients in Stavanger and Warsaw.
      Differences between rural and urban sites explained most of the observed
      variation in leaf chemistry, followed by differences between regions. Highest
      leaf accumulation of elements was found in Warsaw, but also composition of
      elements differed between the cities. Overall, species showed similar patterns of
      element accumulation, but differed in accumulation of specific elements. These
      differences could in part be explained by differences in epicuticular waxes and
      PM accumulation. Expected source of elements and their chemical characteristics
      did not explain the observed accumulation patterns. A better differentiation
      between elements taken up from soil and air would be required for his. Species
      specific accumulation of elements has to be taken into consideration using leaf
      samples for biomonitoring. 

PMID- 25590130
TI  - Human exposure to mercury in a compact fluorescent lamp manufacturing area: By
      food (rice and fish) consumption and occupational exposure.
AB  - To investigate human Hg exposure by food consumption and occupation exposure in a
      compact fluorescent lamp (CFL) manufacturing area, human hair and rice samples
      were collected from Gaohong town, Zhejiang Province, China. The mean values of
      total mercury (THg) and methylmercury (MeHg) concentrations in local cultivated
      rice samples were significantly higher than in commercial rice samples which
      indicated that CFL manufacturing activities resulted in Hg accumulation in local
      rice samples. For all of the study participants, significantly higher THg
      concentrations in human hair were observed in CFL workers compared with other
      residents. In comparison, MeHg concentrations in human hair of residents whose
      diet consisted of local cultivated rice were significantly higher than those who
      consumed commercial rice. These results demonstrated that CFL manufacturing
      activities resulted in THg accumulation in the hair of CFL workers. However, MeHg
      in hair were mainly affected by the sources of rice of the residents.

PMID- 25590131
TI  - Promiscuous RNA binding ensures effective encapsidation of APOBEC3 proteins by
      HIV-1.
AB  - The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3)
      proteins are cell-encoded cytidine deaminases, some of which, such as APOBEC3G
      (A3G) and APOBEC3F (A3F), act as potent human immunodeficiency virus type-1 (HIV
      1) restriction factors. These proteins require packaging into HIV-1 particles to
      exert their antiviral activities, but the molecular mechanism by which this
      occurs is incompletely understood. The nucleocapsid (NC) region of HIV-1 Gag is
      required for efficient incorporation of A3G and A3F, and the interaction between
      A3G and NC has previously been shown to be RNA-dependent. Here, we address this
      issue in detail by first determining which RNAs are able to bind to A3G and A3F
      in HV-1 infected cells, as well as in cell-free virions, using the unbiased
      individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP)
      method. We show that A3G and A3F bind many different types of RNA, including HIV
      1 RNA, cellular mRNAs and small non-coding RNAs such as the Y or 7SL RNAs.
      Interestingly, A3G/F incorporation is unaffected when the levels of packaged HIV
      1 genomic RNA (gRNA) and 7SL RNA are reduced, implying that these RNAs are not
      essential for efficient A3G/F packaging. Confirming earlier work, HIV-1 particles
      formed with Gag lacking the NC domain (Gag DeltaNC) fail to encapsidate A3G/F.
      Here, we exploit this system by demonstrating that the addition of an assortment
      of heterologous RNA-binding proteins and domains to Gag DeltaNC efficiently
      restored A3G/F packaging, indicating that A3G and A3F have the ability to engage
      multiple RNAs to ensure viral encapsidation. We propose that the rather
      indiscriminate RNA binding characteristics of A3G and A3F promote functionality
      by enabling recruitment into a wide range of retroviral particles whose packaged
      RNA genomes comprise divergent sequences. 

PMID- 25590133
TI  - Overexpression of tau downregulated the mRNA levels of Kv channels and improved
      proliferation in N2A cells.
AB  - Microtubule binding protein tau has a crucial function in promoting the assembly
      and stabilization of microtubule. Besides tuning the action potentials, voltage
      gated K+ channels (Kv) are important for cell proliferation and appear to play a
      role in the development of cancer. However, little is known about the possible
      interaction of tau with Kv channels in various tissues. In the present study, tau
      plasmids were transiently transfected into mouse neuroblastoma N2A cells to
      explore the possible linkages between tau and Kv channels. This treatment led to
      a downregulation of mRNA levels of several Kv channels, including Kv2.1, Kv3.1,
      Kv4.1, Kv9.2, and KCNH4, but no significant alteration was observed for Kv5.1 and
      KCNQ4. Furthermore, the macroscopic currents through Kv channels were reduced by
      36.5% at +60 mV in tau-transfected N2A cells. The proliferation rates of N2A
      cells were also improved by the induction of tau expression and the incubation of
      TEA (tetraethylammonium) for 48 h by 120.9% and 149.3%, respectively. Following
      the cotransfection with tau in HEK293 cells, the mRNA levels and corresponding
      currents of Kv2.1 were significantly declined compared with single Kv2.1
      transfection. Our data indicated that overexpression of tau declined the mRNA
      levels of Kv channels and related currents. The effects of tau overexpression on
      Kv channels provided an alternative explanation for low sensitivity to anti
      cancer chemicals in some specific cancer tissues.

PMID- 25590132
TI  - Considerations on the current universal vaccination policy against hepatitis A in
      Greece after recent outbreaks.
AB  - Greece is the only European Union member state that in 2008 included hepatitis A
      (HAV) vaccine in the routine national childhood immunization program (NCIP).
      Given that the resources allocated to public health have dramatically decreased
      since 2008 and that Greece is a low endemicity country for the disease, the
      benefit from universal vaccination has been questioned. The aim of this paper is
      to summarize the available epidemiological data of the disease for 1982-2013, and
      discuss the effects of universal vaccination on disease morbidity. Descriptive
      analysis, ARIMA modeling and time series intervention analysis were conducted
      using surveillance data of acute HAV. A decreasing trend of HAV notification rate
      over the years was identified (p<0.001). However, universal vaccination (~ 80%
      vaccine coverage of children) had no significant effect on the annual number of
      reported cases (p = 0.261) and has resulted to a progressive increase of the
      average age of infection in the general population. The mean age of cases before
      the inclusion of the vaccine to NCIP (24.1 years, SD = 1.5) was significantly
      lower than the mean age of cases after 2008 (31.7 years, SD = 2.1) (p<0.001). In
      the last decade, one third of all reported cases were Roma (a population
      accounting for 1.5% of the country's total population) and in 2013 three
      outbreaks with 16, 9 and 25 Roma cases respectively, were recorded, indicating
      the decreased effectiveness of the current immunization strategy in this group.
      Data suggest that universal vaccination may need to be re-considered. Probably a
      more cost effective approach would be to implement a program that will include:
      a) vaccination of high risk groups, b) universal vaccination of Roma children and
      improving conditions at Roma camps, c) education of the population and travel
      advice, and d) enhancement of the control measures to increase safety of
      shellfish and other foods. 

PMID- 25590135
TI  - Evaluation of the effect of c.2946+1G>T mutation on splicing in the SCN1A gene.
AB  - Mutations in the SCN1A gene have commonly been associated with a wide range of
      mild to severe epileptic syndromes. They generate a wide spectrum of phenotypes
      ranging from the relatively mild generalized epilepsy with febrile seizures plus
      (GEFS+) to other severe epileptic encephalopathies, including myoclonic epilepsy
      in infancy (SMEI), cryptogenic focal epilepsy (CFE), cryptogenic generalized
      epilepsy (CGE) and a distinctive subgroup termed as severe infantile multifocal
      epilepsy (SIMFE). The present study was undertaken to investigate the potential
      effects of a transition in the first nucleotide at the donor splice site of
      intron 15 of the SCN1A gene leading to CGES. Functional analyses using site
      directed mutagenesis by PCR and subsequent ex-vivo splicing assays, revealed that
      the c.2946+1G>T mutation lead to a total skipping of exon 15. The exclusion of
      this exon did not alter the reading frame but induced the deletion of the amino
      acids (853 Leu -971 Val) which are a major part in the fourth, fifth and sixth
      transmembrane segments of the SCN1A protein. The theoretical implications of the
      splice site mutations predicted with the bioinformatic tool human splice finder
      were investigated and compared with the results obtained by the cellular assay. 

PMID- 25590134
TI  - Dynamic ocular surface and lacrimal gland changes induced in experimental murine
      dry eye.
AB  - Dry eye disease can be a consequence of lacrimal gland insufficiency in Sjogren's
      Syndrome or increased tear film evaporation despite normal lacrimal gland
      function. To determine if there is a correlation between severity effects in
      these models and underlying pathophysiological responses, we compared the time
      dependent changes in each of these parameters that occur during a 6 week period.
      Dry eye was induced in 6-week-old female C57BL/6 mice by exposing them to an
      Intelligently Controlled Environmental System (ICES). Sixty mice were housed in
      ICES for 1, 2, 4 and 6 weeks respectively. Twelve were raised in normal
      environment and received subcutaneous injections of scopolamine hydrobromide
      (SCOP) 3 times daily for 5 days. Another sixty mice were housed in a normal
      environment and received no treatment. Corneal fluorescein staining along with
      corneal MMP-9 and caspase-3 level measurements were performed in parallel with
      the TUNEL assay. Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-alpha, IFN-gamma
      and TGF-beta2 levels were estimated by real-time PCR measurements of conjunctival
      and lacrimal gland samples (LGs). Immunohistochemistry of excised LGs along with
      flow cytometry in cervical lymph nodes evaluated immune cell infiltration. Light
      and transmission electron microscopy studies evaluated LGs cytoarchitectural
      changes. ICES induced corneal epithelial destruction and apoptosis peaked at 2
      weeks and kept stable in the following 4 weeks. In the ICES group, lacrimal gland
      proinflammatory cytokine level increases were much lower than those in the SCOP
      group. In accord with the lower proinflammatory cytokine levels, in the ICES
      group, lacrimal gland cytosolic vesicular density and size exceeded that in the
      SCOP group. ICES and SCOP induced murine dry eye effects became progressively
      more severe over a two week period. Subsequently, the disease process stabilized
      for the next four weeks. ICES induced local effects in the ocular surface, but
      failed to elicit lacrimal gland inflammation and cytoarchitectural changes, which
      accounts for less dry eye severity in the ICES model than that in the SCOP model.

PMID- 25590137
TI  - Rewriting the mechanism of JAK2 activation.

PMID- 25590136
TI  - The Use of a Circular Side Stapling Technique in Laparoscopic Low Anterior
      Resection for Rectal Cancer: Experience of 30 Serial Cases.
AB  - The double-stapling technique using a circular stapler (CS) to create an end-to
      end anastomosis is currently used widely in laparoscopic-assisted rectal surgery.
      However, a high rate of anastomotic failure has been reported. We report new side
      to-side anastomosis creation using a CS, the so-called circular side stapling
      technique (CST). After excising the rectum at the oral and anal sides of the
      tumor with a linear stapler, a side-to-side colorectal anastomosis was made on
      the anterior wall of the rectosigmoid colon and the anterior or posterior wall of
      the rectum with a CS. Between 2012 and 2013, we recorded 30 serial cases of
      rectal-sigmoid or rectal cancer that were treated with laparoscopic-assisted
      surgeries using this method. In the 30 cases, the mean age was 68 +/- 12 years,
      operating time was 288 +/- 80 minutes, and blood loss was 66 +/- 67 mL. None of
      the patients suffered from anastomosis leakage or postoperative anastomotic
      bleeding, and none complained of their stool habits. Three months after the last
      surgery in this cohort, no anastomosis strictures were reported. Based on these
      results, we propose an alternative method of side-to-side anastomosis for low
      anterior resection by using a CS to prevent staple overlap. Our experience
      indicates that the CST is easy and safe. Therefore, this method is a useful
      alternative to the current method used in laparoscopic surgery. 

PMID- 25590138
TI  - Synthesis and properties of SmO0.5F0.5BiS2 and enhancement in Tc in La1
      ySmyO0.5F0.5BiS2.
AB  - The crystal structure and properties of a new member of the oxybismuth sulfide
      family SmO(0.5)F(0.5)BiS(2) are reported here. The compounds SmO(1-x)F(x)BiS(2)
      (x = 0.0 and 0.5) are isostructural with LaOBiS(2) and crystallize in the
      CeOBiS(2)-type structure (P4/nmm). Sm substitution in LaO(0.5)F(0.5)BiS(2) (La1
      ySmyO(0.5)F(0.5)BiS(2)) leads to a gradual decrease in the a-lattice constant;
      however, the c-lattice constant does not show such a gradual trend. Enhancement
      in T(c) is achieved upon partial substitution of La by the smaller Sm ion. A
      maximum T(c) ~ 4.6 K was observed for composition with y = 0.8. Disobeying this
      trend, Tc disappears unexpectedly in the composition SmO(0.5)F(0.5)BiS(2) (y =
      1.0). Both the undoped and F-doped (x = 0.0 and 0.5) compounds are paramagnetic,
      exhibiting semiconducting behavior down to 2 K.

PMID- 25590139
TI  - The association between breast tissue optical content and mammographic density in
      pre- and post-menopausal women.
AB  - Mammographic density (MD), associated with higher water and lower fat content in
      the breast, is strongly related to breast cancer risk. Optical attenuation
      spectroscopy (OS) is a non-imaging method of evaluating breast tissue composition
      by red and near-infrared light transmitted through the breast that, unlike
      mammography, does not involve radiation. OS provides information on wavelength
      dependent light scattering of tissue and on absorption by water, lipid, oxy-,
      deoxy-hemoglobin. We propose that OS could be an alternative marker of breast
      cancer risk and that OS breast tissue measures will be associated with MD. In the
      present analysis, we developed an algorithm to estimate breast tissue composition
      and light scattering parameters using a spectrally constrained global fitting
      procedure employing a diffuse light transport model. OS measurements were
      obtained from 202 pre- and post-menopausal women with normal mammograms. Percent
      density (PD) and dense area (DA) were measured using Cumulus. The association
      between OS tissue composition and PD and DA was analyzed using linear regression
      adjusted for body mass index. Among pre-menopausal women, lipid content was
      significantly inversely associated with square root transformed PD (beta = -0.05,
      p = 0.0002) and DA (beta = -0.05, p = 0.019); water content was significantly
      positively associated with PD (beta = 0.06, p = 0.008). Tissue oxygen saturation
      was marginally inversely associated with PD (beta = -0.03, p = 0.057) but
      significantly inversely associated with DA (beta = -0.10, p = 0.002). Among post
      menopausal women lipid and water content were significantly associated
      (negatively and positively, respectively) with PD (beta lipid = -0.08, beta water
      = 0.14, both p<0.0001) and DA (beta lipid = -0.10, p<0.0001; beta water = 0.11, p
      = 0.001). The association between OS breast content and PD and DA is consistent
      with more proliferation in dense tissue of younger women, greater lipid content
      in low density tissue and higher water content in high density tissue. OS may be
      useful for assessing physiologic tissue differences related to breast cancer
      risk, particularly when mammography is not feasible or easily accessible.

PMID- 25590140
TI  - alpha-Actinin-3: why gene loss is an evolutionary gain.

PMID- 25590143
TI  - Triggers and signaling cross-talk controlling cell death commitment.

PMID- 25590144
TI  - Flexible graphene based microwave attenuators.
AB  - We demonstrate flexible 3 dB and 6 dB microwave attenuators using multilayer
      graphene grown by the chemical vapor deposition method. On the basis of the
      characterized results of multilayer graphene and graphene-Au ohmic contacts, the
      graphene attenuators are designed and measured. The flexible graphene-based
      attenuators have 3 dB and 6 dB attenuation with a return loss of less than -15 dB
      at higher than 5 GHz. The devices have shown durability in a bending cycling test
      of 100 times. The circuit model of the attenuator based on the characterized
      results matches the experimental results well. 

PMID- 25590142
TI  - Associations between schistosomiasis and the use of human waste as an
      agricultural fertilizer in China.
AB  - BACKGROUND: Human waste is used as an agricultural fertilizer in China and
      elsewhere. Because the eggs of many helminth species can survive in environmental
      media, reuse of untreated or partially treated human waste, commonly called night
      soil, may promote transmission of human helminthiases. METHODOLOGY/PRINCIPAL
      FINDINGS: We conducted an open cohort study in 36 villages to evaluate the
      association between night soil use and schistosomiasis in a region of China where
      schistosomiasis has reemerged and persisted despite control activities. We tested
      2,005 residents for Schistosoma japonicum infection in 2007 and 1,365 residents
      in 2010 and interviewed heads of household about agricultural practices each
      study year. We used an intervention attributable ratio framework to estimate the
      association between night soil use and S. japonicum infection. Night soil use was
      reported by half of households (56% in 2007 and 46% in 2010). Village night soil
      use was strongly associated with human S. japonicum infection in 2007. We
      estimate cessation of night soil use would lead to a 49% reduction in infection
      prevalence in 2007 (95% CI: 12%, 71%). However, no association between night soil
      and schistosomiasis was observed in 2010. These inconsistent findings may be due
      to unmeasured confounding or temporal shifts in the importance of different
      sources of S. japonicum eggs on the margins of disease elimination.
      CONCLUSIONS/SIGNIFICANCE: The use of untreated or partially treated human waste
      as an agricultural fertilizer may be a barrier to permanent reductions in human
      helminthiases. This practice warrants further attention by the public health
      community.

PMID- 25590141
TI  - Inference of quantitative models of bacterial promoters from time-series reporter
      gene data.
AB  - The inference of regulatory interactions and quantitative models of gene
      regulation from time-series transcriptomics data has been extensively studied and
      applied to a range of problems in drug discovery, cancer research, and
      biotechnology. The application of existing methods is commonly based on implicit
      assumptions on the biological processes under study. First, the measurements of
      mRNA abundance obtained in transcriptomics experiments are taken to be
      representative of protein concentrations. Second, the observed changes in gene
      expression are assumed to be solely due to transcription factors and other
      specific regulators, while changes in the activity of the gene expression
      machinery and other global physiological effects are neglected. While convenient
      in practice, these assumptions are often not valid and bias the reverse
      engineering process. Here we systematically investigate, using a combination of
      models and experiments, the importance of this bias and possible corrections. We
      measure in real time and in vivo the activity of genes involved in the FliA-FlgM
      module of the E. coli motility network. From these data, we estimate protein
      concentrations and global physiological effects by means of kinetic models of
      gene expression. Our results indicate that correcting for the bias of commonly
      made assumptions improves the quality of the models inferred from the data.
      Moreover, we show by simulation that these improvements are expected to be even
      stronger for systems in which protein concentrations have longer half-lives and
      the activity of the gene expression machinery varies more strongly across
      conditions than in the FliA-FlgM module. The approach proposed in this study is
      broadly applicable when using time-series transcriptome data to learn about the
      structure and dynamics of regulatory networks. In the case of the FliA-FlgM
      module, our results demonstrate the importance of global physiological effects
      and the active regulation of FliA and FlgM half-lives for the dynamics of FliA
      dependent promoters. 

PMID- 25590145
TI  - Detection of pathogenic Escherichia coli in samples collected at an abattoir in
      Zaria, Nigeria and at different points in the surrounding environment.
AB  - Pathogenic Escherichia coli can be released with the wastes coming from
      slaughterhouses into the environment, where they can persist. We investigated the
      presence of diarrheagenic E. coli in specimens taken at an abattoir located in
      the Zaria region, Nigeria, in samples of water from the river Koreye, where the
      effluent from the abattoir spills in, and vegetable specimens taken at a nearby
      farm. All the isolated E. coli were assayed for the production of Shiga toxins
      (Stx) by using the Ridascreen verotoxin Immunoassay and by PCR amplification of
      genes associated with the diarrheagenic E. coli. Three strains from the rectal
      content of two slaughtered animals and a cabbage were positive for the presence
      of the Stx-coding genes. Additionally we have isolated one Enteroaggregative E.
      coli (EAggEC) from the abattoir effluent and two Subtilase-producing E. coli from
      the slaughterhouse's effluent and a sample of carrots. Our results provide
      evidence that pathogenic E. coli can contaminate the environment as a result of
      the discharge into the environment of untreated abattoir effluent, representing a
      reservoir for STEC and other diarrheagenic E. coli favouring their spread to
      crops. 

PMID- 25590146
TI  - Reducing environmental tobacco smoke exposure of preschool children: a randomized
      controlled trial of class-based health education and smoking cessation counseling
      for caregivers.
AB  - OBJECTIVES: To assess counseling to caregivers and classroom health education
      interventions to reduce environmental tobacco smoke exposure of children aged 5-6
      years in China. METHODS: In a randomized controlled trial in two preschools in
      Changsha, China, 65 children aged 5-6 years old and their smoker caregivers (65)
      were randomly assigned to intervention (n = 33) and control (no intervention)
      groups (n = 32). In the intervention group, caregivers received self-help
      materials and smoking cessation counseling from a trained counselor, while their
      children were given classroom-based participatory health education. Children's
      urinary cotinine level and the point prevalence of caregiver quitting were
      measured at baseline and after 6 months. RESULTS: At the 6-month follow-up,
      children's urinary cotinine was significantly lower (Z = -3.136; p = 0.002) and
      caregivers' 7-day quit rate was significantly higher (34.4% versus 0%) (p <
      0.001; adjusted OR = 1.13; 95% CI: 1.02-1.26) in the intervention than control
      group. CONCLUSIONS: Helping caregivers quitting smoke combined with classroom
      based health education was effective in reducing children's environmental tobacco
      smoke exposure. Larger-scale trials are warranted.

PMID- 25590147
TI  - Substance use, mental disorders and physical health of Caribbeans at-home
      compared to those residing in the United States.
AB  - This study compares the health conditions of domestic Caribbeans with those
      living in the United States to explore how national context and migration
      experiences might influence substance use (i.e., alcohol or drug) and other
      mental and physical health conditions. The study is based upon probability
      samples of non-institutionalized Caribbeans living in the United States (1621),
      Jamaica (1216) and Guyana (2068) 18 years of age and over. Employing descriptive
      statistics and multivariate analytic procedures, the results revealed that
      substance use and other physical health conditions and major depressive disorder
      and mania vary by national context, with higher rates among Caribbeans living in
      the United States. Context and generation status influenced health outcomes.
      Among first generation black Caribbeans, residing in the United States for a
      longer length of time is linked to poorer health outcomes. There were different
      socio-demographic correlates of health among at-home and abroad Caribbeans. The
      results of this study support the need for additional research to explain how
      national context, migratory experiences and generation status contribute to
      understanding substance use and mental disorders and physical health outcomes
      among Caribbean first generation and descendants within the United States,
      compared to those remaining in the Caribbean region. 

PMID- 25590148
TI  - The effect of PM10 on allergy symptoms in allergic rhinitis patients during
      spring season.
AB  - BACKGROUND: Asian sand dust (ASD) that originates in the Mongolian Desert in the
      spring induces serious respiratory health problems throughout East Asia (China,
      Korea, Japan). PM10 (particulate matter with an aerodynamic diameter <10 MUm) is
      a major air pollutant component in ASD. We studied the effects of PM10 on allergy
      symptoms in patients with allergic rhinitis during the spring season, when ASD
      frequently develops. METHODS: We investigated the changes in allergic symptoms in
      108 allergic patients and 47 healthy subjects by comparing their 120-day symptom
      scores from February to May 2012. At the same time, the contributions of pollen
      count and PM10 concentration were also assessed. We also compared symptom scores
      before and 2 days after the daily PM10 concentration was >100 MUg/m3. RESULTS:
      The PM10 concentration during the 120 days was <150 MUg/m3. No significant
      correlations were observed between changes in the PM10 concentration and allergic
      symptom scores (p > 0.05). However, allergic symptoms were significantly
      correlated with outdoor activity time (p < 0.001). CONCLUSIONS: These results
      demonstrate that a PM10 concentration <150 MUg/m3 did not influence allergy
      symptoms in patients with allergic rhinitis during the 2012 ASD season.

PMID- 25590150
TI  - Metabolic dysregulation. Driving the obese asthma phenotype in adolescents?

PMID- 25590149
TI  - Integrative proteomics and targeted transcriptomics analyses in cardiac
      endothelial cells unravel mechanisms of long-term radiation-induced vascular
      dysfunction.
AB  - Epidemiological data from radiotherapy patients show the damaging effect of
      ionizing radiation on heart and vasculature. The endothelium is the main target
      of radiation damage and contributes essentially to the development of cardiac
      injury. However, the molecular mechanisms behind the radiation-induced
      endothelial dysfunction are not fully understood. In the present study, 10-week
      old C57Bl/6 mice received local X-ray heart doses of 8 or 16 Gy and were
      sacrificed after 16 weeks; the controls were sham-irradiated. The cardiac
      microvascular endothelial cells were isolated from the heart tissue using
      streptavidin-CD31-coated microbeads. The cells were lysed and proteins were
      labeled with duplex isotope-coded protein label methodology for quantification.
      All samples were analyzed by LC-ESI-MS/MS and Proteome Discoverer software. The
      proteomics data were further studied by bioinformatics tools and validated by
      targeted transcriptomics, immunoblotting, immunohistochemistry, and serum
      profiling. Radiation-induced endothelial dysfunction was characterized by
      impaired energy metabolism and perturbation of the insulin/IGF-PI3K-Akt signaling
      pathway. The data also strongly suggested premature endothelial senescence,
      increased oxidative stress, decreased NO availability, and enhanced inflammation
      as main causes of radiation-induced long-term vascular dysfunction. Detailed data
      on molecular mechanisms of radiation-induced vascular injury as compiled here are
      essential in developing radiotherapy strategies that minimize cardiovascular
      complications. 

PMID- 25590151
TI  - Clearing the air. Smoking and incident asthma in adults.

PMID- 25590152
TI  - Lung-protective ventilation in acute respiratory distress syndrome. How soon is
      now?

PMID- 25590153
TI  - Toward improved diagnosis of early asthma.

PMID- 25590154
TI  - Novel approaches are needed to develop tomorrow's antibacterial therapies.
AB  - Society faces a crisis of rising antibiotic resistance even as the pipeline of
      new antibiotics has been drying up. Antibiotics are a public trust; every
      individual's use of antibiotics affects their efficacy for everyone else. As
      such, responses to the antibiotic crisis must take a societal perspective. The
      market failure of antibiotics is due to a combination of scientific challenges to
      discovering and developing new antibiotics, unfavorable economics, and a hostile
      regulatory environment. Scientific solutions include changing the way we screen
      for new antibiotics. More transformationally, developing new treatments that seek
      to disarm pathogens without killing them, or that modulate the host inflammatory
      response to infection, will reduce selective pressure and hence minimize
      resistance emergence. Economic transformation will require new business models to
      support antibiotic development. Finally, regulatory reform is needed so that
      clinical development programs are feasible, rigorous, and clinically relevant.
      Pulmonary and critical care specialists can have tremendous impact on the
      continued availability of effective antibiotics. Encouraging use of molecular
      diagnostic tests to allow pathogen-targeted, narrow-spectrum antibiotic therapy,
      using short rather than unnecessarily long course therapy, reducing inappropriate
      antibiotic use for probable viral infections, and reducing infection rates will
      help preserve the antibiotics we have for future generations. 

PMID- 25590155
TI  - An official American Thoracic Society policy statement: managing conscientious
      objections in intensive care medicine.
AB  - RATIONALE: Intensive care unit (ICU) clinicians sometimes have a conscientious
      objection (CO) to providing or disclosing information about a legal,
      professionally accepted, and otherwise available medical service. There is little
      guidance about how to manage COs in ICUs. OBJECTIVES: To provide clinicians,
      hospital administrators, and policymakers with recommendations for managing COs
      in the critical care setting. METHODS: This policy statement was developed by a
      multidisciplinary expert committee using an iterative process with a diverse
      working group representing adult medicine, pediatrics, nursing, patient advocacy,
      bioethics, philosophy, and law. MAIN RESULTS: The policy recommendations are
      based on the dual goals of protecting patients' access to medical services and
      protecting the moral integrity of clinicians. Conceptually, accommodating COs
      should be considered a "shield" to protect individual clinicians' moral integrity
      rather than as a "sword" to impose clinicians' judgments on patients. The
      committee recommends that: (1) COs in ICUs be managed through institutional
      mechanisms, (2) institutions accommodate COs, provided doing so will not impede a
      patient's or surrogate's timely access to medical services or information or
      create excessive hardships for other clinicians or the institution, (3) a
      clinician's CO to providing potentially inappropriate or futile medical services
      should not be considered sufficient justification to forgo the treatment against
      the objections of the patient or surrogate, and (4) institutions promote open
      moral dialogue and foster a culture that respects diverse values in the critical
      care setting. CONCLUSIONS: This American Thoracic Society statement provides
      guidance for clinicians, hospital administrators, and policymakers to address
      clinicians' COs in the critical care setting.

PMID- 25590156
TI  - Severe adult respiratory distress syndrome from Goodpasture syndrome. Survival
      using extracorporeal membrane oxygenation.

PMID- 25590157
TI  - A solemn declaration from the World Alliance against Antibiotic Resistance.

PMID- 25590158
TI  - Development of a hypercoagulable status in patients undergoing off-pump lung
      transplantation despite prolonged conventional coagulation tests.

PMID- 25590160
TI  - IL-33-dependent Th2 response after rhinovirus infection in asthma: more
      information needed.

PMID- 25590159
TI  - Measurement of serum calprotectin in stable patients predicts exacerbation and
      lung function decline in cystic fibrosis.

PMID- 25590161
TI  - IL-33-dependent type 2 inflammation in asthma exacerbations.

PMID- 25590162
TI  - Reply: IL-33-dependent type 2 inflammation in asthma exacerbations.

PMID- 25590163
TI  - American Thoracic Society patient information series. Other therapies for sleep
      apnea.
AB  - Treatment is needed for obstructive sleep apnea (OSA) because untreated OSA can
      result in serious health problems. Continuous positive airway pressure (CPAP)
      therapy is the most common treatment used for obstructive sleep apnea (OSA). (see
      ATS Patient Series http://patients.thoracic.org/wp-content/uploads/
      2014/03/obstructive-sleep-apnea.pdf) For those who cannot use CPAP or want to try
      another option, there are other therapies that can work for people with OSA.

PMID- 25590168
TI  - Correction to "assessing the dual activity of a chalcone-phthalocyanine
      conjugate: design, synthesis, and antivascular and photodynamic properties".

PMID- 25590169
TI  - Innovative use of membrane contactor as condenser for heat recovery in carbon
      capture.
AB  - The gas-liquid membrane contactor generally used as a nonselective gas absorption
      enhancement device is innovatively proposed as a condenser for heat recovery in
      liquid-absorbent-based carbon capture. The membrane condenser is used as a heat
      exchanger to recover the latent heat of the exiting vapor from the desorber, and
      it can help achieve significant energy savings when proper membranes with high
      heat-transfer coefficients are used. Theoretical thermodynamic analysis of mass
      and heat transfer in the membrane condensation system shows that heat recovery
      increases dramatically as inlet gas temperature rises and outlet gas temperature
      falls. The optimal split mass flow rate is determined by the inlet gas
      temperature and the overall heat-transfer coefficient in the condensation system.
      The required membrane area is also strongly dependent on the overall heat
      transfer coefficient, particularly at higher inlet gas temperatures. Mass
      transfer across the membrane has an insignificant effect on heat transfer and
      heat recovery, suggesting that membrane wetting may not be an issue when a
      membrane condenser is used for heat recovery. Our analysis provides important
      insights into the energy recovery performance of the membrane condensation system
      as well as selection of operational parameters, such as split mass flow rate and
      membrane area, thickness, and thermal conductivity. 

PMID- 25590170
TI  - Elaboration, validation and standardization of the five to fifteen (FTF)
      questionnaire in a Danish population sample.
AB  - The five to fifteen (FTF) is a parent questionnaire developed to assess ADHD, its
      common comorbid conditions and associated problems in children and adolescents.
      The present study examined (1) the psychometric properties of scores on the new
      teacher version of the FTF, (2) competing models of the FTF subdomain structure
      and (3) the psychometric properties and utility of scores on the newly developed
      FTF impact questions. Parents (n=4258) and teachers (n=1298) of Danish children
      and adolescents (ages 5 to 17 years), selected using simple random sampling,
      completed the FTF. In the largest study of the FTF to date, parent and teacher
      scores had acceptable psychometric properties. The FTF subdomains were organized
      into six domains labelled cognitive skills, motor/perception,
      emotion/socialization/behaviour, attention, literacy skills and activity control
      and analysis of these domains may provide additional information when applying
      the FTF in the future. The impact questions yielded information above and beyond
      that provided by symptom count alone and appeared to increase the ability of the
      FTF to identify at risk children and adolescents. 

PMID- 25590164
TI  - mTOR coordinates protein synthesis, mitochondrial activity and proliferation.
AB  - Protein synthesis is one of the most energy consuming processes in the cell. The
      mammalian/mechanistic target of rapamycin (mTOR) is a serine/threonine kinase
      that integrates a multitude of extracellular signals and intracellular cues to
      drive growth and proliferation. mTOR activity is altered in numerous pathological
      conditions, including metabolic syndrome and cancer. In addition to its well
      established role in regulating mRNA translation, emerging studies indicate that
      mTOR modulates mitochondrial functions. In mammals, mTOR coordinates energy
      consumption by the mRNA translation machinery and mitochondrial energy production
      by stimulating synthesis of nucleus-encoded mitochondria-related proteins
      including TFAM, mitochondrial ribosomal proteins and components of complexes I
      and V. In this review, we highlight findings that link mTOR, mRNA translation and
      mitochondrial functions. 

PMID- 25590171
TI  - Oculomotor performance in children with high-functioning Autism Spectrum
      Disorders.
AB  - Sensorimotor issues are of increasing focus in the assessment and treatment of
      Autism Spectrum Disorders (ASD). The oculomotor system is a sensorimotor network
      that can provide insights into functional neurobiology and has well-established
      methodologies for investigation. In this study, we assessed oculomotor
      performance among children with high functioning ASD and typically developing
      children, ages 6-12 years. Children with ASD exhibited greater horizontal saccade
      latency and greater phase lag during vertical smooth pursuit. Saccades and smooth
      pursuit are mediated by spatially distant brain regions and the long-fiber tracts
      connecting them, many of which are implicated in ASD. Training paradigms for
      oculomotor deficits have shown positive outcomes in other clinical populations,
      and deficits described here may provide useful targets for interventions. 

PMID- 25590172
TI  - Postural control during standing reach in children with Down syndrome.
AB  - The purpose of the present study was to investigate the dynamic postural control
      of children with Down syndrome (DS). Specifically, we compared postural control
      and goal-directed reaching performance between children with DS and typically
      developing children during standing reach. Standing reach performance was
      analyzed in three main phases using the kinematic and kinetic data collected from
      a force plate and a motion capture system. Fourteen children with DS, age and
      gender matched with fourteen typically developing children, were recruited for
      this study. The results showed that the demand of the standing reach task
      affected both dynamic postural control and reaching performance in children with
      DS, especially in the condition of beyond arm's length reaching. More postural
      adjustment strategies were recruited when reaching distance was beyond arm's
      length. Children with DS tended to use inefficient and conservative strategies
      for postural stability and reaching. That is, children with DS perform standing
      reach with increased reaction and execution time and decreased amplitudes of
      center of pressure displacements. Standing reach resembled functional balance
      that is required in daily activities. It is suggested to be considered as a part
      of strength and balance training program with graded task difficulty. 

PMID- 25590173
TI  - Variations in cognitive demand affect heart rate in typically developing children
      and children at risk for developmental coordination disorder.
AB  - BACKGROUND: Developmental coordination disorder (DCD) is a diagnosis for children
      who present with movement difficulties, but are of normal intelligence without
      neurological deficits. Previous studies have demonstrated that children with DCD
      exhibit perceptual deficits and lower cognition performance. To date, their
      autonomic nervous system (ANS) responses during tasks requiring cognitive and
      perceptual effort have not been compared to typically developing children (TDC).
      OBJECTIVE: The present study investigated heart rate variability (HRV) as a
      marker for ANS response differences between DCD and TDC, and the impact of
      different levels of task difficulty. METHODS: Participants were 60 individuals (9
      10 years); 30 children at risk for DCD, and 30 TDC. Each participant performed
      two tasks each of which demanded enhanced cognitive effort: a visual signal
      detection task and a digit memory task-each task had two levels of difficulty,
      low (LD) and high (HD). Heart rate responses were continuously recorded during
      performance of each task. Frequency domain analysis and heart rate sample entropy
      (SampEn) were computed to determine ANS responses in each of the tasks. RESULTS:
      HRV differences were detected between the two levels of task difficulty, LD and
      HD, for the visual signal detection task, but not for the digit memory task. HRV
      differences between LD and HD conditions were greater for TDC children than DCD
      when engaged in visual signal detection task, compare to the memory task.
      INTERPRETATION: The results suggest that children at risk for DCD may show
      decreased HRV as a marker for altered ANS responses and potential deficits in the
      linkage between their perceptions and actions.

PMID- 25590174
TI  - Initial evaluation of a new plastic pancreatic duct stent for endoscopic
      ultrasonography-guided placement.
AB  - There are currently no plastic pancreatic duct stents that have been designed for
      endoscopic ultrasonography (EUS)-guided placement. This study prospectively
      evaluated the feasibility and efficacy of a new, single-pigtail, plastic stent.
      Eight patients with main pancreatic duct stricture or stenotic
      pancreatojejunostomy underwent EUS-guided placement of the pancreatic duct stent.
      The stent was placed successfully in all cases (8/8). Treatment success was
      achieved in all cases (8/8). A mild adverse event associated with the procedure
      was observed in one patient but there were no other adverse events during a mean
      follow-up of 7.4 months. This new pancreatic duct stent appears to be feasible
      and effective for EUS-guided stenting. 

PMID- 25590175
TI  - A two-step multidisciplinary approach to treat recurrent esophageal strictures in
      children with epidermolysis bullosa dystrophica.
AB  - In children with severe generalized recessive dystrophic epidermolysis bullosa
      (RDEB), esophageal scarring leads to esophageal strictures with dysphagia,
      followed by malnutrition and delayed development. We describe a two-step
      multidisciplinary therapeutic approach to overcome malnutrition and growth
      retardation. In Step 1, under general anesthesia, orthograde balloon dilation of
      the esophagus is followed by gastrostomy creation using a direct puncture
      technique. In Step 2, further esophageal strictures are treated by retrograde
      dilation via the established gastrostomy; this step requires only a short
      sedation period. A total of 12 patients (median age 7.8 years, range 6 weeks to
      17 years) underwent successful orthograde balloon dilation of esophageal
      strictures combined with direct puncture gastrostomy. After 12 and 24 months in
      11 children, a substantial improvement of growth and nutrition was achieved (body
      mass index [BMI] standard deviation score [SDS] + 0.59 and + 0.61, respectively).
      In one child, gastrostomy was removed because of skin ulcerations after 10 days.
      Recurrent esophageal strictures were treated successfully in five children. The
      combined approach of balloon dilation and gastrostomy is technically safe in
      children with RDEB, and helps to promote catch-up growth and body weight. In
      addition, recurrent esophageal strictures can be treated successfully without
      general anesthesia in a retrograde manner via the established gastrostomy. 

PMID- 25590176
TI  - EUS-guided sutured gastropexy for transgastric ERCP (ESTER) in patients with Roux
      en-Y gastric bypass: a novel, single-session, minimally invasive approach.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP)
      in patients with Roux-en-Y gastric bypass (RYGB) is a challenging procedure.
      Available techniques are hampered by limited success, need for a separate delayed
      session for ERCP, potential complications,and/or invasiveness. This paper reports
      on a novel technique that involves endoscopic ultrasound(EUS)-guided access into
      the remnant stomach and sutured gastropexy for transgastric ERCP in a single
      combined session. PATIENTS AND METHODS: A total of 10 patients with RYGB
      underwent transgastric ERCP using the novel technique. EUS was used to puncture
      the excluded stomach through the gastric pouch or jejunum,the stomach was
      insufflated, and a direct percutaneous gastrostomy puncture followed by sutured
      gastropexy was performed. ERCP was performed by passing a duodenoscope through
      the gastrostomy. RESULTS: Technical success of EUS-assisted sutured gastropexy
      was achieved in nine patients (90 %),with immediate, same-session ERCP in all
      nine.There were no adverse events. CONCLUSIONS: EUS-assisted, fluoroscopically
      guided sutured gastropexy is a safe and effective method to obtain access into
      the excluded gastric remnant for same-session transgastric ERCP inpatients with
      Roux-en-Y gastric bypass anatomy.

PMID- 25590177
TI  - Magnetic-controlled capsule endoscopy vs. gastroscopy for gastric diseases: a two
      center self-controlled comparative trial.
AB  - BACKGROUND AND STUDY AIMS: We developed a novel magnetic-controlled capsule
      endoscopy (MCE) system for use in the human stomach. The aim of the current study
      was to compare the diagnostic accuracy of MCE with that of standard gastroscopy
      for gastric diseases. PATIENTS AND METHODS: A total of 68 patients were enrolled
      in this self-controlled trial. Patients were evaluated by both MCE and
      gastroscopy. Gastroscopy was performed 4 - 24 hours after completion of the MCE
      examination. RESULTS: The positive percent agreement between MCE and gastroscopy
      was 96.0 %, and the negative percent agreement was 77.8 %. The overall agreement
      was 91.2 % with a kappa value of 0.765 (P < 0.001). A total of 68 pathological
      findings were detected, of which 53 were identified by both methods. The MCE and
      standard gastroscopy missed seven and eight findings, respectively. CONCLUSIONS:
      MCE showed a diagnostic accuracy similar to that of standard gastroscopy. These
      results suggest that MCE is a promising alternative to gastroscopy for
      noninvasive screening of gastric diseases.Clinical trial registration number:
      NCT01903629.

PMID- 25590178
TI  - Prophylactic somatostatin can reduce incidence of post-ERCP pancreatitis:
      multicenter randomized controlled trial.
AB  - BACKGROUND AND STUDY AIM: Post-endoscopic retrograde cholangiopancreatography
      (ERCP) pancreatitis (PEP) remains the most common complication of ERCP.
      Somatostatin may inhibit pancreatic secretion and has been tested for PEP
      prophylaxis. However, the results of previous studies are inconsistent. The aim
      of the current study was to investigate whether somatostatin can reduce the
      incidence of PEP. PATIENTS AND METHODS: The study was a multicenter, open-label,
      randomized controlled trial. A total of 908 patients with normal amylase levels
      who were undergoing ERCP were randomized to receive somatostatin 250 MUg bolus
      injection before ERCP and 250 MUg/hour intravenous infusion for 11 hours after
      ERCP (somatostatin group) or no somatostatin treatments (control group). The
      incidences of PEP and hyperamylasemia were compared in the two groups. RESULTS:
      The full analysis set included 900 patients (445 in the somatostatin group, 455
      in the control group). PEP developed in 34 patients (7.5 %) in the control group
      (95 % confidence interval [CI] 5.4 % - 10.3 %) and in 18 patients (4.0 %) in the
      somatostatin group (95 %CI 2.6 % - 6.3 %; P = 0.03). Hyperamylasemia occurred in
      46 patients (10.1 %) in the control group (95 %CI 7.7 % - 13.2 %) and in 27
      patients (6.1 %) in the somatostatin group (95 %CI 4.2 % - 8.7 %; P = 0.03). No
      perforation or death occurred during the study. CONCLUSIONS: This study showed
      that somatostatin was effective and safe for the prevention of PEP and
      hyperamylasemia in ERCP patients.(ClinicalTrials.gov number, NCT01431781).

PMID- 25590179
TI  - Self-expandable metallic stents vs. plastic stents for endoscopic biliary
      drainage in hepatocellular carcinoma.
AB  - BACKGROUND AND STUDY AIMS: The patency of self-expandable metallic stents (SEMS)
      is known to be better than plastic stents in the palliation of malignant biliary
      obstruction. However, data are scarce for obstructive jaundice caused by
      hepatocellular carcinoma (HCC). This study aimed to compare SEMSs and plastic
      stents for the palliation of obstructive jaundice in unresectable HCC. PATIENTS
      AND METHODS: A total of 96 patients who underwent endoscopic retrograde biliary
      drainage with SEMSs or plastic stents were included in this retrospective
      analysis. The rate of successful biliary drainage, adverse events, stent patency
      duration, and patient survival were compared between the SEMS (n = 36) and
      plastic stent (n = 60) groups. RESULTS: The rate of successful biliary drainage
      was similar between the SEMS and plastic stent groups (25/36 [69.4 %] vs. 39/60
      [65.0 %]; P = 0.655). Adverse events occurred in 6 patients (16.7 %) in the SEMS
      group and 13 patients (21.7 %) in the plastic stent group (P = 0.552). The median
      patency duration was also similar between the two groups (60 vs. 68 days; P =
      0.396). The median patient survival was longer in the plastic stent group than in
      the SEMS group (123 vs. 48 days; P = 0.005). CONCLUSIONS: SEMSs were not superior
      to plastic stents for the palliation of malignant biliary obstruction in HCC with
      regard to successful drainage, stent patency, and adverse events. Patient
      survival was better in the plastic stent group. Given the lower cost, plastic
      stents could be a favorable option for malignant biliary obstruction caused by
      HCC.

PMID- 25590180
TI  - Prospective evaluation of ERCP performance: results of a nationwide quality
      registry.
AB  - BACKGROUND AND STUDY AIMS: Despite significant interest from health care
      authorities, patient organizations, and insurance companies, data on procedural
      outcome and quality of endoscopic retrograde cholangiopancreatography (ERCP) in
      general and academic practice are sparse. The aims of this study were to assess
      procedural outcome of ERCP within a large prospective registry in The
      Netherlands, and to evaluate associations between endoscopist-related factors and
      procedural outcome. METHODS: All endoscopists performing ERCP in The Netherlands
      were invited to register their ERCPs over a 1-year period using the Rotterdam
      Assessment Form for ERCP (RAF-E). The primary outcome measure was procedural
      success. A priori difficulty level of the procedure was classified according to
      Schutz. Baseline characteristics of the endoscopist (e. g. previous experience)
      were recorded at study entry. Regression analysis was performed to identify
      predictors of procedural outcome. RESULTS: A total of 8575 ERCPs were registered
      by 171 endoscopists from 61 centers, constituting about 50 % of all ERCPs
      performed nationally during the study period. Overall procedural success was 85.8
      %. Intact papillary anatomy was present in 5106 patients (59.5 %): procedural
      success in this subgroup of patients was 83.4 % vs. 89.4 % after sphincterotomy
      (P < 0.001). Multivariate logistic regression identified "degree of difficulty,"
      "intact papillary anatomy," and "previous ERCP failure" to be independently
      associated with procedural failure. "Yearly volume of ERCPs" and "trainee
      involvement" were independently associated with success. CONCLUSIONS: The
      nationwide prospective RAF-E registry proved to be a valuable tool to gain
      insight into procedural outcome of ERCPs.

PMID- 25590181
TI  - Long-term mortality and recurrence after colorectal cancer surgery with
      preoperative stenting: a Danish nationwide cohort study.
AB  - BACKGROUND AND STUDY AIMS: Self-expanding metal stents (SEMS) used as a bridge to
      surgery for obstructive colorectal cancer (CRC) have fallen under suspicion for
      inducing tumor dissemination, and thereby increasing recurrence risk and long
      term mortality. The aim of this study was to compare overall mortality and CRC
      recurrence in patients receiving preoperative SEMS vs. patients undergoing urgent
      resection. PATIENTS AND METHODS: This was a Danish, nationwide, population-based
      cohort study (2005 - 2010). For patients with CRC who survived the first 30 days
      after resection, the long-term survival in terms of mortality rate ratios was
      assessed using Cox regression with adjustment for important covariates. For
      patients with Dukes' A - C disease only, recurrence risk was similarly assessed
      using incidence rate ratios. RESULTS: The 5-year survival was 49 % among 581
      patients with preoperative SEMS and 40 % among 3333 patients undergoing urgent
      resection, corresponding to an adjusted mortality rate ratio of 0.98 (95 %
      confidence interval [CI] 0.90 to 1.07). For patients with Dukes' stage A - C
      disease, the 5-year recurrence risk was 39 % among 286 patients after
      preoperative SEMS and 30 % among 1627 patients after urgent resection,
      corresponding to an adjusted incidence rate ratio of 1.12 (95 %CI 0.99 to 1.28).
      CONCLUSIONS: Long-term mortality associated with the use of SEMS as a bridge to
      surgery was comparable to that of urgent resection. SEMS use may be associated
      with an increased CRC recurrence risk.

PMID- 25590183
TI  - Effects of a hemostatic powder hemospray on coagulation and clot formation.
AB  - BACKGROUND AND STUDY AIMS: Hemospray (Cook Medical Inc., Winston-Salem, North
      Carolina, USA) is a novel, hemostatic, powder spray that has been developed for
      gastrointestinal use. The powder is thought to achieve hemostasis by
      concentrating clotting factors and forming a mechanical plug on the injured blood
      vessel. However, no detailed studies on the hemostatic mode of action have been
      performed. The aim of this study was to examine the effects of Hemospray on
      coagulation and clot formation both in vitro and in vivo. MATERIALS AND METHODS:
      Recalcification time, thromboelastometry using EXTEM and INTEM assays, and plasma
      coagulation tests (activated partial thromboplastin time and prothrombin time)
      were carried out on blood samples mixed with Hemospray, and compared with talcum
      powder (negative control) and kaolin (positive control) at 1 mg/mL and 10 mg/mL.
      Scanning electron microscopy (SEM) and light microscopy were performed on in
      vitro thrombi and on gastric thrombi from an animal model of gastrointestinal
      hemorrhage treated with Hemospray. RESULTS: The median recalcification time of
      whole blood was 187.5 seconds. The addition of 1 mg/mL and 10 mg/mL Hemospray
      significantly shortened this time (median 60 and 45 seconds, respectively; P <
      0.05). The median clotting time of whole blood, measured using the INTEM assay,
      was 160 seconds (interquartile range [IQR] 159 - 176.5) and this was also
      significantly reduced by the addition of Hemospray (91 seconds [IQR 84 - 102]; P
      = 0.005). The plasma prothrombin time of 11.6 seconds was significantly reduced
      by Hemospray (9.5 seconds; P = 0.011). SEM of in vivo clots demonstrated that
      Hemospray rapidly interacted with whole blood, forming one confluent mass over
      the bleeding site. In sufficient amounts, Hemospray was able to deform and pack
      erythrocytes. CONCLUSIONS: Hemospray covered the bleeding site and enhanced clot
      formation in vivo, and shortened coagulation time in vitro. Elaboration of these
      unique properties in clinical practice will help to optimize future endoscopic
      hemostasis with Hemospray.

PMID- 25590182
TI  - Randomized multicenter study of multiple plastic stents vs. covered self
      expandable metallic stent in the treatment of biliary stricture in chronic
      pancreatitis.
AB  - BACKGROUND AND STUDY AIMS: The use of covered self-expandable metallic stents
      (cSEMS) in benign biliary indications is evolving. The aim of the study was to
      assess the safety and feasibility of cSEMS compared with multiple plastic stents
      in the treatment of benign biliary stricture (BBS) caused by chronic
      pancreatitis. PATIENTS AND METHODS: This was a prospective, multicenter,
      randomized study of 60 patients with BBS caused by chronic pancreatitis. All
      patients received an initial plastic stent before randomization. At
      randomization, the stent was replaced either with a single cSEMS or three plastic
      stents. After 3 months, the position of the cSEMS was checked or another three
      plastic stents were added. At 6 months after randomization, all stents were
      removed. Clinical follow-up including abdominal ultrasound and laboratory tests
      were performed at 6 months and 2 years after stent removal. RESULTS: Two patients
      dropped out of the cSEMS group before stent removal. In April 2014, the median
      follow-up was 40 months (range 1 - 66 months). The 2-year, stricture-free success
      rate was 90 % (95 % confidence interval [CI] 72 % - 97 %) in the plastic stent
      group and 92 % (95 %CI 70 % - 98 %) in the cSEMS group (P = 0.405). There was one
      late recurrence in the plastic stent group 50 months after stent removal. Stent
      migration occurred three times (10 %) in the plastic stent group and twice in the
      cSEMS group (7 %; P = 1.000). CONCLUSION: A 6-month treatment with either six 10
      Fr plastic stents or with one 10-mm cSEMS produced good long-term relief of
      biliary stricture caused by chronic pancreatitis.Study registered at
      ClinicalTrials.gov (NCT01085747).

PMID- 25590184
TI  - Thienopyridine derivatives as risk factors for bleeding following high risk
      endoscopic treatments: Safe Treatment on Antiplatelets (STRAP) study.
AB  - BACKGROUND AND STUDY AIMS: The optimal method of perioperative management of
      antiplatelet agents during endoscopic procedures that carry a high risk of
      bleeding is still controversial. The aim of this study was to evaluate the safety
      of continuing aspirin treatment during these procedures in an Asian population.
      PATIENTS AND METHODS: A multicenter, prospective, observational cohort study was
      conducted at six high volume endoscopy centers in Japan. The study included
      patients at high risk of thromboembolism who were regularly taking antiplatelet
      agents (e. g. thienopyridine derivatives and aspirin). Enrolled patients
      continued their aspirin therapy, and underwent endoscopic procedures that had a
      high risk of bleeding for treatment of lesions in the upper and lower
      gastrointestinal tracts. The primary end point was the rate of major bleeding
      complications after endoscopic procedures. RESULTS: The study was terminated in
      accordance with predetermined safety criteria because 7 of 28 consecutive
      patients experienced major bleeding complications (25.0 %; 95 % confidence
      interval 10.7 % - 44.9 %). All major bleeding complications occurred following
      endoscopic submucosal dissection (ESD; 6 stomach, 1 colon). Univariate analysis
      showed that postoperative administration of thienopyridine derivatives was the
      only significant factor associated with postoperative bleeding (P = 0.01).
      Subanalysis of gastric ESD (23 lesions in 19 patients) confirmed that the
      administration of thienopyridine derivatives (P = 0.01) and that of multiple
      agents (P = 0.02) were the significant factors. All bleeding complications
      (postoperative day 11.2 +/- 3.5) occurred after resuming thienopyridine
      derivative therapy postoperatively (postoperative day 2.3 +/- 2.4). CONCLUSION:
      In Asian patients taking thienopyridine derivatives with aspirin, cautious
      postoperative care is necessary for those undergoing endoscopic procedures that
      are associated with a high risk of bleeding, especially gastric ESD. Continuation
      of aspirin alone during these endoscopic procedures may be acceptable. STUDY
      REGISTRATION: UMIN000009176.

PMID- 25590185
TI  - Determining the adenoma detection rate and adenomas per colonoscopy by
      photography alone: proof-of-concept study.
AB  - BACKGROUND AND STUDY AIMS: The adenoma detection rate (ADR) and adenomas detected
      per colonoscopy (APC) are measures of the quality of mucosal inspection during
      colonoscopy. In a resect and discard policy, pathologic assessment for
      calculation of ADR and APC would not be available. The aim of this study was to
      determine whether ADR and APC calculation based on photography alone is adequate
      compared with the pathology-based gold standard. PATIENTS AND METHODS: A
      prospective, observational, proof-of-concept study was performed in an academic
      endoscopy unit. High definition photographs of consecutive polyps were taken, and
      pathology was estimated by the colonoscopist. Among 121 consecutive patients aged
      >= 50 years who underwent colonoscopy, 268 polyps were removed from 97 patients.
      Photographs of consecutive polyps were reviewed by a second endoscopist. RESULTS:
      The resect and discard policy applied to lesions that were <= 5 mm in size. When
      only photographs of lesions that were ultimately proven to be adenomas were
      included, the reviewer assessed ADR and APC to be lower than that determined by
      pathology (absolute reductions of 6.6 % and 0.17, and relative reductions of 12.6
      % and 13.1 % in ADR and APC, respectively). When all photographs were included
      for calculation of ADR and APC, the reviewer determined the ADR to be 3.3 % lower
      (absolute reduction) and the APC to be the same as the rates determined by
      pathology. CONCLUSIONS: In a simulated resect and discard strategy, a high-level
      detector can document adequate ADR and APC by photography alone.

PMID- 25590186
TI  - Early use of double-guidewire technique to facilitate selective bile duct
      cannulation: the multicenter randomized controlled EDUCATION trial.
AB  - BACKGROUND AND STUDY AIMS: There are no guidelines for the timing of conversion
      from a single-guidewire to a double-guidewire technique to facilitate selective
      bile duct cannulation and reduce post-endoscopic retrograde
      cholangiopancreatography pancreatitis (PEP), when using wire-guided cannulation.
      We investigated whether early conversion to the double-guidewire method, at first
      unintentional insertion of a guidewire into the pancreatic duct, facilitated
      selective bile duct cannulation and reduced PEP compared with repeated single
      guidewire attempts. PATIENTS AND METHODS: A multicenter prospective randomized
      controlled trial included 274 patients with a naive papilla, undergoing
      endoscopic retrograde cholangiography (ERC) using wire-guided cannulation in whom
      there was unintentional insertion of the guidewire into the pancreatic duct. With
      the guidewire still in the duct, patients were randomly assigned to undergo the
      double-guidewire technique or repeated single-wire cannulation. Main outcomes
      were success rates for selective bile duct cannulation and PEP frequency.
      RESULTS: Success rates for selective bile duct cannulation within 10 attempts and
      10 minutes were 75 % and 70 %, respectively, for the early double-guidewire (EDG)
      and repeated single-guidewire (RSG) cannulation groups (relative rate 1.07, 95 %
      confidence interval [95 %CI] 0.93 - 1.24, P = 0.42). Corresponding final
      selective bile duct cannulation rates were 98 % and 97 % (relative rate 1.01, 95
      %CI 0.97 - 1.05, P = 1.00). PEP rates were 20 % and 17 %, respectively, for the
      EDG and RSG cannulation groups (relative risk 1.17, 95 %CI 0.71 - 1.94, P =
      0.53). Double-guidewire cannulation was more effective in patients with malignant
      biliary stricture (relative rate 1.36, 95 %CI 1.05 - 1.77, P = 0.02).
      CONCLUSIONS: During therapeutic ERC using wire-guided cannulation, converting to
      a double-guidewire technique neither facilitated selective bile duct cannulation
      nor decreased PEP incidence compared with repeated use of a single-wire
      technique.

PMID- 25590187
TI  - Utility of intrapapillary capillary loops seen on magnifying narrow-band imaging
      in estimating invasive depth of esophageal squamous cell carcinoma.
AB  - BACKGROUND AND STUDY AIMS: Intrapapillary capillary loops (IPCLs) have been used
      to estimate histopathological atypia and the invasion depth of squamous cell
      carcinoma (SCC). The aim of this study was to evaluate the clinical significance
      of IPCLs. PATIENTS AND METHODS: A total of 358 consecutive patients with
      esophageal neoplasia on magnifying narrow-band imaging (M-NBI) were studied. The
      lesions were categorized according to the IPCL classification of Inoue et al. and
      were subsequently resected. Resected specimens were histopathologically analyzed
      to determine the invasion depth. The inter- and intraobserver agreements in the
      interpretation of IPCL images were also investigated. RESULTS: A total of 446
      lesions were diagnosed on M-NBI as IPCL type V lesions, which were further
      classified as 185 IPCL type V1, 109 type V2, 104 type V3, and 48 type Vn.
      Sensitivity and specificity of IPCL type V1-2 for invasion confined to the
      epithelium or lamina propria mucosa (m1-2) were 89.5 % (95 % confidence interval
      [CI] 85.4 % - 92.7 %) and 79.6 % (95 %CI 72.3 % - 85.7 %), respectively.
      Sensitivity and specificity of IPCL type V3 for invasion confined to the
      muscularis mucosa or slight submucosal invasion (m3-sm1) were 58.7 % and 83.8 %,
      respectively. Sensitivity and specificity of IPCL type Vn for deeper invasion
      (sm2-3) were 55.8 % and 98.6 %, respectively. Interobserver agreement was
      substantial (kappa = 0.609, 0.641, and 0.705), as was intraobserver agreement
      (kappa = 0.705 and kappa = 0.819). CONCLUSION: Changes in the morphology of IPCLs
      on M-NBI correlated with the depth of SCC invasion, and results were reproducible
      and reliable among observers. Identification of IPCL type V1-2 proved useful for
      the intraprocedural identification of m1-2 lesions, which are considered an
      absolute indication for endoscopic resection.

PMID- 25590188
TI  - Wing-shaped plastic stents vs. self-expandable metal stents for palliative
      drainage of malignant distal biliary obstruction: a randomized multicenter study.
AB  - BACKGROUND AND STUDY AIMS: Previous studies have shown superior patency rates for
      self-expandable metal stents (SEMS) compared with plastic stents in patients with
      malignant biliary obstruction. The aim of this study was to compare stent
      patency, patient survival, and complication rates between a newly designed, wing
      shaped, plastic stent and SEMSs in patients with unresectable, malignant, distal,
      biliary obstruction. PATIENTS AND METHODS: A randomized, multicenter trial was
      conducted at four tertiary care centers in Germany. A total of 37 patients
      underwent randomization between March 2010 and January 2013. Patients underwent
      endoscopic retrograde cholangiography with insertion of either a wing-shaped,
      plastic stent without lumen or an SEMS.  RESULTS: Stent failure occurred in 10/16
      patients (62.5 %) in the winged-stent group vs. 4/18 patients (22.2 %) in the
      SEMS group (P = 0.034). The median time to stent failure was 51 days (range 2 -
      92 days) for the winged stent and 80 days (range 28 - 266 days) for the SEMS (P =
      0.002). Early stent failure (< 8 weeks after placement) occurred in 8 patients
      (50 %) vs. 2 patients (11.1 %), respectively (P = 0.022). After obtaining the
      results from this interim analysis, the study was discontinued because of safety
      concerns. CONCLUSIONS: The frequency of stent failure was significantly higher in
      the winged-stent group compared with the SEMS group. A high incidence of early
      stent failure within 8 weeks was observed in the winged-stent group. Thus, the
      winged, plastic stent without central lumen may not be appropriate for mid or
      long term drainage of malignant biliary obstruction. Study registration
      ClinicalTrials.gov (NCT01063634).

PMID- 25590189
TI  - Evaluation of cellular proliferative activity in patients with oral lichen planus
      and hepatitis C through AgNOR method.
AB  - The objective of this study was to evaluate the cellular proliferative potential
      of oral lichen planus (OLP) lesions from patients without hepatitis C virus (HCV)
      by means of AgNOR method, as well as the cellular proliferative potential of the
      normal oral mucosa from patients with HCV, treated or untreated by interferon and
      ribavirin. A cross-sectional study was developed to investigate four groups: 10
      HCV+ patients without clinical signs of OLP who had never been treated for HCV
      infection - Group 1; 10 HCV+ patients that were under interferon and ribavirin
      treatment - Group 2; 15 patients with reticular OLP lesions histopathologically
      confirmed, without HCV - Group 3; and 15 blood donors without HCV infection and
      no clinical signs of OLP GROUP 4 Control Group. The cytological material of all
      groups was collected by the liquid-based cytology technique. Then, the sedimented
      material from each patient was filled with the Nucleolar Organizer Regions
      impregnation by silver method (AgNOR). The count of NORs was performed on 100
      epithelial cell nuclei per patient using the Image Tool(tm) software. The Tukey
      HSD test was used to compare the median value of NORs among the groups and showed
      that the oral mucosa of HCV+ patients previously treated with anti-HCV drugs
      (GROUP 2), presented a higher average number of NORs in relation to others
      (p<0.05). The anti-HCV treatment may be related to increased cell proliferation
      of oral mucosa, indicating a possible relationship between OLP and HCV+ patients
      treated with interferon and ribavirin. 

PMID- 25590190
TI  - Correlation between radiographic area and immunolocation of MMP-2 and MMP-9 in
      unilocular radiographic lesions.
AB  - Unilocular bone cysts are the most common entities affecting the maxillofacial
      region. The mechanism of proliferation and expansion remains unclear.
      Metalloproteinases (MMPs) are associated to diverse pathological conditions. The
      aim of the present study was to correlate the radiographic aspect (area) and the
      presence of MMP-2 and MMP-9 in dentigerous cysts, radicular cysts and
      keratocystic odontogenic tumors. The radiographic area of each lesion was
      calculated using the mathematical formula of the ellipse area. All specimens were
      subjected to immunohistochemical analysis for these enzymes. The average
      radiographic area was 284.17 mm2, 235.81 mm2 and 381.81 mm2, respectively.
      Statistical analyses revealed no association between the immunoreactivity of MMPs
      and radiographic area of the lesions in all pathologies studied, except for MMP-2
      and radicular cysts, for which smaller lesions had increased immunostaining for
      this enzyme. The results demonstrate that quantities of MMP-2 and MMP-9 are
      especially involved with dentigerous and radicular cysts in expansion, whereas
      these enzymes seem to be related to the biological behavior of keratocystic
      odontogenic tumors, indicating invasion and cell proliferation. Moreover, there
      is an inverse association between MMP-2 and MMP-9 in keratocystic odontogenic
      tumors (p=0.03; rs=-0.660), indicating activity in different regions. 

PMID- 25590192
TI  - Effect of trimetaphosphate and fluoride association on hydroxyapatite dissolution
      and precipitation in vitro.
AB  - The present study analyzed the action of sodium trimetaphosphate (TMP) and/or
      fluoride on hydroxyapatite. Hydroxyapatite powder was suspended in different
      solutions: deionized water, 500 ug F/mL, 1,100 ug F/mL, 1%TMP, 3%TMP, 500 ug F/mL
      plus 1%TMP and 500 ug F/mL plus 3%TMP. The pH value of the solutions was reduced
      to 4.0 and after 30 min, raised to 7.0 (three times). After pH-cycling, the
      samples were analyzed by X-ray diffraction and infrared spectroscopy. The
      concentrations of calcium fluoride, fluoride, calcium and phosphorus were also
      determined. Adding 1% or 3% TMP to the solution containing 500 ug F/mL produced a
      higher quantity of calcium fluoride compared to samples prepared in a 1,100 ug
      F/mL solution. Regarding the calcium concentration, samples prepared in solutions
      of 1,100 ug F/mL and 500 ug F/mL plus TMP were statistically similar and showed
      higher values. Using solutions of 1,100 ug F/mL and 500 ug F/mL plus TMP resulted
      in a calcium/phosphorus ratio close to that of hydroxyapatite. It is concluded
      that the association of TMP and fluoride favored the precipitation of a more
      stable hydroxyapatite. 

PMID- 25590193
TI  - Recolonization of mutans Streptococci after application of chlorhexidine gel.
AB  - Streptococcus mutans is specifically suppressed by intensive treatment with
      chlorhexidine gel, but the time for recolonization and the effect on other oral
      bacteria are not totally clear. In this study, recolonization of mutans
      streptococci was evaluated in nine healthy adult volunteers, who were highly
      colonized with this microorganism. Stimulated saliva was collected before
      (baseline) and at 1, 7, 14, 21 and 28 days after application of 1% chlorhexidine
      gel on volunteers' teeth for two consecutive days. On each day, the gel was
      applied using disposable trays for 3 x 5 min with intervals of 5 min between each
      application. Saliva was plated on blood agar to determine total microorganisms
      (TM); on mitis salivarius agar to determine total streptococci (TS) and on mitis
      salivarius agar plus bacitracin to determine mutans streptococci (MS).
      Chlorhexidine was capable of reducing the counts of MS and the proportion of MS
      with regard to total microorganisms (%MS/TM) (p<0.05), but these values did not
      differ statistically from baseline (p>0.05) after 14 days for MS and 21 days for
      %MS/TM. The counts of TM and TS and the proportion of MS to total streptococci
      did not differ statistically from baseline (p>0.05) after chlorhexidine
      treatment. The results suggest that the effect of chlorhexidine gel treatment on
      suppression of mutans streptococci is limited to less than a month in highly
      colonized individuals. 

PMID- 25590191
TI  - Dentin bond strength of a fluoride-releasing adhesive system submitted to pH
      cycling.
AB  - To evaluate the microtensile bond strength (uTBS) of a fluoride-containing
      adhesive system submitted to a pH-cycling and storage time regimen for primary
      outcomes. As secondary outcomes the fluoride released amount was evaluated.
      Twelve dentin surfaces from sound third molar were divided into 2 groups
      according to adhesive systems: Clearfil SE Protect (PB) and Clearfil SE Bond
      (SE). Sticks obtained (1.0 mm2) from teeth were randomly divided into 3 subgroups
      according to storage regimen model: immediate (24h); 5-month deionized water (W);
      and pH-cycling model (C). All sticks were tested for uTBS in a universal testing
      machine. Fluoride concentration was obtained from 1-4 days and 30-day in W and 1
      4 days in demineralization (DE)/remineralization (RE) solutions from C, using a
      fluoride-specific electrode. uTBS and fluoride released data were, respectively,
      submitted to ANOVA in a split plot design and Tukey, and Friedman' tests
      (a=0.05). There was no significant interaction between adhesive system and
      storage regimen for uTBS. W showed the lowest uTBS values. There was no
      significant difference between 24 h and C models for uTBS. There was no
      significant difference between adhesive systems. Failure mode was predominantly
      cohesive within composite for the 24 h and W, for the C group it was mixed for SE
      and cohesive within composite for PB adhesive system. Fluoride concentrations in
      the DE/RE solutions were less than 0.03125 ppm and not detected in W. In
      conclusion, the fluoride-containing adhesive system performed similarly to the
      regular one. Hydrolytic degradation is the main problem with both adhesive
      systems, regardless of fluoride contents. 

PMID- 25590194
TI  - Root canal penetration of a sodium hypochlorite mixture using sonic or ultrasonic
      activation.
AB  - The purpose of this ex vivo study was to determine, in "open" and "closed"
      systems, whether the design has an influence on the penetration length of sodium
      hypochlorite mixed with a radiopaque contrast medium, measured in millimeters,
      when delivered using positive pressure (PP) and using sonic (SI) or passive
      ultrasonic (PUI) activation. Sixty single-rooted teeth were divided into two
      groups: open and closed systems (n=30). Root canal shaping was performed to a
      working length of 17 mm. The samples were divided into three sub-groups (n=10)
      according to irrigant delivery and activation: PP, and SI or PUI activation. By
      using radiographs, penetration length was measured, and vapor lock was assessed.
      For the closed group, the penetration distance means were: PP 15.715 (+/-0.898)
      mm, SI 16.299 (+/-0.738) mm and PUI 16.813 (+/-0.465) mm, with vapor lock
      occurring in 53.3% of the specimens. In the open group, penetration to 17 mm
      occurred in 97.6% of the samples, and no vapor lock occurred. Irrigant
      penetration and distribution evaluation using open and closed systems provide
      significantly different results. For closed systems, PUI is the most effective in
      delivering the irrigant to working length, followed by SI. 

PMID- 25590195
TI  - Monitoring nonsurgical and surgical root canal treatment of teeth with primary
      and secondary infections.
AB  - The aim of this study was to monitor nonsurgical and surgical root canal
      treatment (RCT) of teeth with primary and secondary infections and apical
      periodontitis (AP). This prospective clinical study comprised the treatment of 80
      patients with primary and persistent secondary infections and AP. Of this initial
      sample, forty patients did not return. Periapical index using cone beam computed
      tomography scans (CBCTPAI) was used to aid diagnosis, planning and to determine
      the better therapeutic strategy. Twenty patients (26 teeth) diagnosed with
      primary infection and AP received conventional RCT and were followed up for 10 to
      36 months. Twenty patients (31 teeth) diagnosed with persistent secondary
      infection were submitted to periapical surgical and followed up for 6 to 30
      months. The results showed RCT successful in 19/26 cases with complete AP healing
      (5/26 with partial repair) in 10-36 months of follow up. For the surgically
      managed cases, effectiveness of surgical therapy was detected in 10/31 cases with
      complete healing (10/31 cases with partial repair) within 6-30 months follow up.
      The return of patients for clinical and radiographic follow-up, and obedience to
      the proposed time period was very short from ideal. The levels of success in both
      therapeutic protocols were high. RCT failures were detected even with rigorous
      standard clinical protocols. 

PMID- 25590196
TI  - Manual and rotary instrumentation ability to reduce Enterococcus faecalis
      associated with photodynamic therapy in deciduous molars.
AB  - This aim of this study was to assess the ability of manual or rotary
      instrumentation associated with photodynamic therapy (PDT) to reduce Enterococcus
      faecalis using three combinations of light/photosensitizers: toluidine blue
      O/laser, fuchsin/halogen light and fuchsin/LED. Twenty deciduous molars were
      selected and contaminated with Enterococcus faecalis (McFarland 0.5 scale).
      Working length determination was performed by visual method. The teeth were
      randomly divided into two groups: G1 (n=10): manual instrumentation (Kerr-type
      files) and G2 (n=10): rotary instrumentation (ProTaper system). The bacteria were
      collected three times using sterile paper cones compatible with the anatomic
      diameter of the root canal for 30 s before and after instrumentation and after
      PDT. The samples were diluted in peptone water, seeded on blood agar plates and
      incubated in an oven at 37  degrees C for colony-forming units counting. The
      decrease of E. faecalis counts after instrumentation and after PDT was compared
      using the Wilcoxon test, t-test and Kruskal Wallis test. A significant reduction
      of E. faecalis occurred after manual and rotary instrumentation and after PDT
      using the three combinations of light/photosensitizer (p<0.05). It may be
      concluded that both rotary and manual instrumentation reduced E. faecalis.
      Fuchsin with halogen light or LED irradiation and toluidine blue O with laser
      irradiation can be used to reduce E. faecalis in root canals of primary molars.
      PDT can be used as an adjuvant to conventional endodontic treatment. 

PMID- 25590197
TI  - Analysis of endodontist posture utilizing cinemetry, surface electromyography and
      ergonomic checklists.
AB  - The postural risk factors for dentists include the ease of vision in the
      workplace, cold, vibration and mechanical pressure in tissues, incorrect posture,
      functional fixity, cognitive requirements and work-related organizational and
      psychosocial factors. The objective was to analyze the posture of endodontists at
      the workplace. Eighteen right-handed endodontists aged 25 to 60 years (34+/-3)
      participated in the study. Electromyography, kinemetry, ergonomic scales (RULA
      and Couto's checklist) and biophotogrammetry were used to analyze the posture of
      endodontists during root canal treatment of the maxillary right first and second
      molars using rotary and manual instrumentation. The variations observed in the
      electromyographic activities during the performance of rotary and manual
      techniques suggest that the fibers of the longissimus region, anterior and medium
      deltoid, medium trapezium, biceps, triceps brachii, brachioradialis and short
      thumb abductor muscles underwent adaptations to provide more accurate functional
      movements. Computerized kinemetry and biophotogrammetry showed that, as far as
      posture is concerned, rotary technique was more demanding than the manual
      technique. In conclusion, the group of endodontists evaluated in this study
      exhibited posture disorders regardless of whether the rotary or manual technique
      was used. 

PMID- 25590198
TI  - Impact of intracoronal dentin treatment prior to bleaching on bond strength of
      restorative materials.
AB  - Surface treatment of dentin before the bleaching procedure may affect its
      permeability and influence the bond strength of restorative materials. This study
      evaluated the influence of surface treatment before the bleaching on shear bond
      strength (SBT) of restorative materials to intracoronal dentin. Dentin slabs were
      subjected to surface treatment: no bleaching (control - CON), no surface
      treatment + bleaching (HP), 37% phosphoric acid + bleaching (PA) and Er:YAG laser
      + bleaching (L). After the bleaching procedure, specimens (n=10) were restored
      with: microhybrid composite resin (MH), flowable composite resin (F), and resin
      modified glass-ionomer cement (RMGIC). The shear test was carried out. ANOVA and
      Tukey's test (alpha=0.05) showed significant difference for surface treatment and
      restorative materials (p<0.05). CON presented higher STB and was statistically
      different from HP (p<0.05). PA and L showed intermediate values and were
      statistically similar to CON and HP (p>0.05). STB for MH and F were higher than
      RMGIC (p<0.05), and did not differ from each other (p>0.05). The surface
      treatments with phosphoric acid and Er:YAG laser before the bleaching procedure
      provided shear bond strength at the same level of unbleached dentin and the
      composite resins presented superior bond strength to the intracoronal dentin. 

PMID- 25590199
TI  - A comparison of the bleaching effectiveness of chlorine dioxide and hydrogen
      peroxide on dental composite.
AB  - This study was carried out to verify if composites could be bleached using
      chlorine dioxide as compared with hydrogen peroxide. 3M ESPE Filtek Z350
      Universal Restorative discs were prepared (n=40), with dimensions 5 mm diameter x
      2 mm thickness. The discs were divided into 4 groups of 10 discs each. Color
      assessment was performed by CIEDE2000. The discs were stained with coffee, tea,
      wine and distilled water (control) solutions for 14 days, 5 hours daily. Color
      assessment was repeated on stained discs and followed by bleaching of 5 discs
      from each group using chlorine dioxide and hydrogen peroxide in-office systems.
      Finally, a last color assessment was performed and compared statistically. DE2000
      after bleaching was very close to baseline for both the bleaching agents,
      although chlorine dioxide showed better results than hydrogen peroxide. After
      staining, there was a clinically significant discoloration (?E2000>=3.43) for the
      tea, coffee and wine groups, and discoloration (?E2000) was seen more in the wine
      group as compared to tea and coffee. Overall, the control group (distilled water)
      had the least color change in the three intervals. After bleaching, the color in
      all specimens returned close to the baseline. The color differences between
      bleaching and baseline were less than 3.43 for all groups. The obtained results
      show that chlorine dioxide is slightly superior to hydrogen peroxide in the
      bleaching of composites, while maintaining the shade of the composite close to
      the baseline. 

PMID- 25590200
TI  - Physicochemical properties of a methacrylate-based dental adhesive incorporated
      with epigallocatechin-3-gallate.
AB  - This study aimed to evaluate the influence of epigallocatechin-3-gallate (EGCG)
      incorporation on the physicochemical properties of a methacrylate-based dental
      adhesive. EGCG was added to Adper Easy One (3M-ESPE) except in control group, to
      obtain concentrations of 0.01% w/w and 0.1% w/w of EGCG-doped adhesives. For
      water sorption (WS) and solubility (SL) surveys, resin discs were assayed
      following ISO recommendations (n=10). The degree of conversion (DC) was analyzed
      by FTIR whereas flexural strength (FS) was tested by three-point bending with bar
      specimens (n=10). Data were subjected to one-way ANOVA and Tukey's test (p<0.05).
      No significant difference in the DC, WS and FS were found between the different
      concentrations of EGCG (p>0.05). Adhesives containing 0.1% or 0.01% of EGCC
      demonstrated similar values of SL (p>0.05) and higher than those found for
      adhesive without EGCC (p<0.05). In conclusion, the addition of EGCC to adhesive
      reduced the solubility without affecting the other evaluated properties. 

PMID- 25590201
TI  - Degradation of resin composites in a simulated deep cavity.
AB  - The aim of this study was to analyze the sorption and solubility of a nanofilled
      (Filtek Z350) and a midifilled (Filtek P60) resin composite in oral environment
      like substances, in a simulated deep cavity. A cylindrical cavity prepared in a
      bovine incisor root was incrementally filled with resin composites. The obtained
      resin composite cylinders were cut perpendicularly to the axis to obtain 1-mm
      thick discs that were divided into fifteen groups (n=5) according to depth (1, 2,
      3, 4 and 5 mm) and immersion media (distilled water - DW, artificial saliva - AS
      and lactic acid - LA). The sorption and solubility were calculated based on ISO
      4049:2000. Additionally, the degree of conversion (DC%) was calculated by FT-IR
      spectroscopy. Data were analyzed using multifactor analysis of variance (MANOVA)
      followed by Tukey's HSD post-hoc test and linear regression analysis (a=0.05).
      The DC% was higher for the midifilled resin composite and was negatively
      influenced by cavity depth (p<0.05). The nanofilled resin composite presented
      higher sorption and solubility than did the midifilled (p<0.05). The immersion
      media influenced the sorption and the solubility as follows: LA>AS>DW, (p<0.05).
      Both phenomena were influenced by cavity depth, with the sorption and solubility
      increasing from 1 to 5 mm (p<0.05). The degradation of resin composite
      restorations may be greater in the deepest regions of class II restorations when
      the composite is exposed to organic acids present in the oral biofilm (lactic
      acid). 

PMID- 25590202
TI  - Effect of 4-(N,N-dimethylamino)phenethyl alcohol on degree of conversion and
      cytotoxicity of photo-polymerized CQ-based resin composites.
AB  - The aim of this study was to evaluate the degree of conversion (DC) and the
      cytotoxicity of photo-cured experimental resin composites containing 4-(N,N
      dimethylamino)phenethyl alcohol (DMPOH) combined to the camphorquinone (CQ)
      compared with ethylamine benzoate (EDAB). The resin composites were mechanically
      blended using 35 wt% of an organic matrix and 65 wt% of filler loading. To this
      matrix was added 0.2 wt% of CQ and 0.2 wt% of one of the reducing agents tested.
      5x1 mm samples (n=5) were previously submitted to DC measurement and then pre
      immersed in complete culture medium without 10% (v/v) bovine serum for 1 h or 24
      h at 37  degrees C in a humidifier incubator with 5% CO2 and 95% humidity to
      evaluate the cytotoxic effects of experimental resin composites using the MTT
      assay on immortalized human keratinocytes cells. As a result of absence of normal
      distribution, the statistical analysis was performed using the nonparametric
      Kruskal-Wallis to evaluate the cytotoxicity and one-way analysis of variance to
      evaluate the DC. For multiple comparisons, cytotoxicity statistical analyses were
      submitted to Student-Newman-Keuls and DC analysis to Tukey's HSD post-hoc test
      (?=0.05). No significant differences were found between the DC of DMPOH (49.9%)
      and EDAB (50.7%). 1 h outcomes showed no significant difference of the cell
      viability between EDAB (99.26%), DMPOH (94.85%) and the control group (100%).
      After 24 h no significant difference were found between EDAB (48.44%) and DMPOH
      (38.06%), but significant difference was found compared with the control group
      (p>0.05). DMPOH presented similar DC and cytotoxicity compared with EDAB when
      associated with CQ. 

PMID- 25590203
TI  - Does maintaining a bottle of adhesive without the lid significantly reduce the
      solvent content?
AB  - This study aimed to evaluate the effect of maintaining a bottle of adhesive
      without its lid on the solvent loss of the etch-and-rinse adhesive systems. Three
      2-step etch-and-rinse adhesives with different solvents (acetone, ethanol or
      butanol) were used in this study. Drops of each adhesive were placed on an
      analytical balance and the adhesive mass was recorded until equilibrium was
      achieved (no significant mass alteration within time). The solvent content of
      each adhesive and evaporation rate of solvents were measured (n=3). Two bottles
      of each adhesive were weighted. The bottles were maintained without their lids
      for 8 h in a stove at 37 oC, after which the mass loss was measured. Based on
      mass alteration of drops, acetone-based adhesive showed the highest solvent
      content (46.5%, CI 95%: 35.8-54.7) and evaporation rate (1.11 %/s, CI95%: 0.63
      1.60), whereas ethanol-based adhesive had the lowest values (10.1%, CI95%: 4.3
      16.0; 0.03 %/s CI95%: 0.01-0.05). However, none of the adhesives bottles
      exhibited significant mass loss after sitting for 8 h without their lids (% from
      initial content; acetone - 96.5, CI 95%: 91.8-101.5; ethanol - 99.4, CI 95%: 98.4
      100.4; and butanol - 99.3, CI 95%: 98.1-100.5). In conclusion, maintaining the
      adhesive bottle without lid did not induce significant solvent loss, irrespective
      the concentration and evaporation rate of solvent. 

PMID- 25590204
TI  - Toothache, associated factors, and its impact on Oral Health-Related Quality of
      Life (OHRQoL) in preschool children.
AB  - The aim of this study was to assess the prevalence of toothache, associated
      factors and impact of this condition on the Child Oral Health Related Quality of
      Life (COHRQoL) in preschoolers. The study was carried out in Santa Maria, Brazil,
      during the National Children's Vaccination Day, and 534 children aged 0 to 5
      years were included. Clinical variables included dental caries and dental trauma.
      A questionnaire was responded by the parents and provided information about
      several socioeconomic indicators, dental service use and toothache. Toothache was
      collected by the question: "Has your child ever had a toothache - Yes or no?".
      Data on COHRQoL were assessed using the Brazilian version of the Early Childhood
      Oral Health Impact Scale (ECOHIS). Multivariable Logistic regression models were
      performed to assess the association between the predictor variables and outcomes.
      The prevalence of toothache was 10.11% (95% CI: 7.55% - 12.68%). Older children
      had a higher chance of presenting dental pain (OR 2.72; 95% CI: 1.01 - 7.56), as
      well as children with caries experience (OR 3.43; 95% CI: 1.81 - 6.52). Moreover,
      children who had not visited the dental service in the last 6 months were less
      likely to present toothache (OR 0.51; 95% CI: 0.28 - 0.95). The presence of
      dental pain negatively affects the COHRQoL; those with toothache presented a
      higher chance of having higher impact on the total scores of ECOHIS (OR 4.18; 95%
      CI: 1.76 - 9.95) than those without toothache. Similar observation was found for
      the child section of the questionnaire (OR 5.54; 95% CI: 2.15 - 14.24). Toothache
      negatively affects COHRQoL and is associated with caries experience, age and use
      of dental service. 

PMID- 25590205
TI  - Effect of the parafunctional occlusal loading and crown height on stress
      distribution.
AB  - The aim of this study was to assess, by the three-dimensional finite element
      method, the influence of crown-to-implant ratio and parafunctional occlusal
      loading on stress distribution in single external hexagon implant-supported
      prosthesis. Computer-aided design software was used to confection three models.
      Each model was composed of a block bone and an external hexagon implant (5x10.0
      mm) with screw-retained implant prostheses, varying the height crown: 10, 12.5
      and 15 mm. Finite element analysis software was used to generate the finite
      element mesh and to establish the loading and boundary conditions. Normal (200 N
      axial and 100 N oblique load) and parafunctional forces (1,000 N axial and 500 N
      oblique load) were applied. The results were visualized by von Mises and maximum
      principal stress. In comparison with the normal occlusal force, the
      parafunctional occlusal force induced an increase in stress concentration and
      magnitude on implant (platform and first threads) and screw (neck). The cortical
      bone showed the highest tensile stress under parafunctional force (oblique load).
      The stress concentration increased as the crown height increased. It was
      concluded that: increasing the C/I increased stress concentration in both implant
      components and cortical bone; parafunctional loading increased between 4-5 times
      the value of stresses in bone tissue compared with functional loading; the type
      of loading variation factor is more influential than the crown-to-implant factor.

PMID- 25590206
TI  - Pattern of maxillofacial fractures in severe multiple trauma patients: a 7-year
      prospective study.
AB  - The incidence of facial trauma is high. This study has the primary objective of
      documenting and cataloging maxillofacial fractures in polytrauma patients. From a
      total of 1229 multiple trauma cases treated at the Emergency Room of the Santo
      Antonio Hospital - Oporto Hospital Center, Portugal, between August 2001 and
      December 2007, 251 patients had facial wounds and 209 had maxillofacial
      fractures. Aged ranged form 13 to 86 years. The applied selective method was
      based on the presence of facial wound with Abbreviated Injury Scale >=1. Men had
      a higher incidence of maxillofacial fractures among multiple trauma patients
      (86.6%) and road traffic accidents were the primary cause of injuries (69.38%).
      Nasoorbitoethmoid complex was the most affected region (67.46%) followed by the
      maxilla (57.42%). The pattern and presentation of maxillofacial fractures had
      been studied in many parts of the world with varying results. Severe multiple
      trauma patients had different patterns of maxillofacial injuries. The number of
      maxillofacial trauma is on the rise worldwide as well as the incidence of
      associated sequelae. Maxillofacial fractures on multiple trauma patients were
      more frequent among males and in road traffic crashes. Knowing such data is
      elementary. The society should have a key role in the awareness of individuals
      and in prevention of road traffic accidents. 

PMID- 25590207
TI  - Technique of framework cemented on prepared abutments to obtain passive fit at
      fixed complete denture: a 2-year follow-up report.
AB  - The passive fit of implant-supported dentures is fundamental to the
      rehabilitation success due the absence of the periodontal ligament in
      osseointegrated implants. Many techniques to obtain passive fit have been
      reported in the literature, some inaccessible for the clinicians and dental
      laboratories. This case report presents a technique to fabricate fixed complete
      dentures aiming at obtain passive fit with reduced time and cost, but without
      demerit for the aesthetics, function and longevity. A 40-year-old woman was
      referred for treatment presenting some teeth in the maxilla and an edentulous
      mandible, reporting eating problems related to instability and little retention
      of the mandibular complete denture. Treatment based on the reverse planning was
      performed to guide the rehabilitation with a complete mandibular fixed complete
      denture and maxillary occlusal plane adjustment. The framework of the fixed
      complete denture was manufactured luting a cast metal bar above the prepared
      titanium cylinder abutments using resin cement. The aim of this technique was to
      obtain a fixed complete denture with passive fit presenting positive esthetic and
      functional outcomes after 2 years of follow-up. 

PMID- 25590208
TI  - Obturation over an S1 ProTaper instrument fragment in a mandibular molar with
      three years of follow-up.
AB  - This case report describes root canal filling performed over a large S1 ProTaper
      file fragment in a second mandibular molar with irreversible pulpitis. An S1
      ProTaper file was fractured during the instrumentation of the mesiobuccal canal.
      Approximately 10 mm of file fragment remained in the apical and middle thirds of
      the canal. The obturation was performed over this fragment using
      thermomechanically compacted gutta-percha and sealer. Radiographic findings and
      the absence of clinical signs and symptoms at 3-year follow up indicated
      successful treatment. Cone-beam computed tomography images revealed absence of
      periapical lesion and details of intracanal file fragment related to root
      fillings and apex morphology. In this case, the presence of a large intracanal
      fractured instrument did not have a negative impact on the endodontic prognosis
      during the follow up evaluation period. 

PMID- 25590209
TI  - Effects of Aerosolized Adenosine 5'-Triphosphate in Smokers and Patients With
      COPD.
AB  - BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) stimulates vagal C and
      Adelta fibers in the lung, resulting in pronounced bronchoconstriction and cough
      mediated by P2X2/3 receptors located on vagal sensory nerve terminals. We
      investigated the effects of nebulized ATP on cough and symptoms in control
      subjects, healthy smokers, and patients with COPD and compared these responses to
      the effects of inhaled adenosine, the metabolite of ATP. METHODS: We studied the
      effects of inhaled ATP and adenosine monophosphate (AMP) on airway caliber,
      perception of dyspnea assessed by the Borg score, cough sensitivity, and ATP in
      exhaled breath condensate in healthy nonsmokers (n = 10), healthy smokers (n =
      14), and patients with COPD (n = 7). RESULTS: In comparison with healthy
      subjects, ATP induced more dyspnea, cough, and throat irritation in smokers and
      patients with COPD, and the effects of ATP were more pronounced than those of
      AMP. The concentration of ATP in the exhaled breath condensate of patients with
      COPD was elevated compared with that of healthy subjects. CONCLUSIONS: Smokers
      and patients with COPD manifest hypersensitivity to extracellular ATP, which may
      play a mechanistic role in COPD.

PMID- 25590210
TI  - Two-step cyanomethylation protocol: convenient access to functionalized aryl- and
      heteroarylacetonitriles.
AB  - A two-step protocol has been developed for the introduction of cyanomethylene
      groups to metalated aromatics through the intermediacy of substituted isoxazoles.
      A palladium-mediated cross-coupling reaction was used to introduce the isoxazole
      unit, followed by release of the cyanomethylene function under thermal or
      microwave-assisted conditions. The intermediate isoxazoles were shown to be
      amenable to further functionalization prior to deprotection of the sensitive
      cyanomethylene motif, allowing access to a wide range of aryl- and heteroaryl
      substituted acetonitrile building blocks. 

PMID- 25590211
TI  - Metformin reverts the secretion of CXCL8 induced by TNF-alpha in primary cultures
      of human thyroid cells: an additional indirect anti-tumor effect of the drug.
AB  - CONTEXT: Metformin displays both direct and indirect anti-tumor effects. CXCL8 is
      a crucial downstream mediator of Nuclear-Factor-kappaB signaling related to the
      growth and progression of thyroid cancers. Targeting CXCL8 results in prolonged
      survival and reduced metastatic spread in in-vivo animal models of thyroid
      tumors. OBJECTIVE: This study aimed to evaluate whether metformin inhibits the
      secretion of CXCL8 induced by Tumor-Necrosis-Factor-alpha (TNF-alpha) in primary
      cultures of normal and tumor human thyroid cells as well as in thyroid cancer
      cell lines. METHODS: Normal human thyrocytes, papillary thyroid cancer cells, and
      thyroid cancer cell lines (TPC-1 and BCPAP) were stimulated with TNF-alpha (10
      ng/mL) alone or in combination with metformin (0.01, 0.1, 1, 2.5, 5, and 10mM).
      CXCL8 levels were measured in the cell supernatants after 24 hours. RESULTS:
      Metformin significantly and dose-dependently inhibited the TNF-alpha-induced
      CXCL8 secretion in both normal thyrocytes (ANOVA: F = 42.04; P < .0001) and
      papillary thyroid cancer cells (ANOVA: F = 21.691; P < .0001) but not in TPC-1
      and BCPAP cell lines. CONCLUSION: Metformin inhibits the TNF-alpha-induced CXCL8
      secretion in primary cultures of normal thyroid cells and differentiated thyroid
      cancer cells at least of the most frequent poorly aggressive phenotype. The
      recruitment of neutrophils within the thyroid gland is a crucial metastasis
      promoting factor, and it depends on the amount of CXCL8 produced by both tumor
      cells and by the more abundant normal thyroid cells exposed to TNF-alpha. Thus,
      the here-reported inhibiting effect of metformin on TNF-alpha-induced CXCL8
      secretion could be considered as a further indirect anticancer property of the
      drug.

PMID- 25590212
TI  - Pharmacological management of obesity: an endocrine Society clinical practice
      guideline.
AB  - OBJECTIVE: To formulate clinical practice guidelines for the pharmacological
      management of obesity. PARTICIPANTS: An Endocrine Society-appointed Task Force of
      experts, a methodologist, and a medical writer. This guideline was co-sponsored
      by the European Society of Endocrinology and The Obesity Society. EVIDENCE: This
      evidence-based guideline was developed using the Grading of Recommendations,
      Assessment, Development, and Evaluation (GRADE) system to describe the strength
      of recommendations and the quality of evidence. CONSENSUS PROCESS: One group
      meeting, several conference calls, and e-mail communications enabled consensus.
      Committees and members of the Endocrine Society, the European Society of
      Endocrinology, and The Obesity Society reviewed and commented on preliminary
      drafts of these guidelines. Two systematic reviews were conducted to summarize
      some of the supporting evidence. CONCLUSIONS: Weight loss is a pathway to health
      improvement for patients with obesity-associated risk factors and comorbidities.
      Medications approved for chronic weight management can be useful adjuncts to
      lifestyle change for patients who have been unsuccessful with diet and exercise
      alone. Many medications commonly prescribed for diabetes, depression, and other
      chronic diseases have weight effects, either to promote weight gain or produce
      weight loss. Knowledgeable prescribing of medications, choosing whenever possible
      those with favorable weight profiles, can aid in the prevention and management of
      obesity and thus improve health.

PMID- 25590214
TI  - Arterial norepinephrine concentration is inversely and independently associated
      with insulin clearance in obese individuals with metabolic syndrome.
AB  - CONTEXT: Impaired insulin clearance contributes to the hyperinsulinemia of
      obesity, yet relatively little is known concerning the pathophysiological
      determinants of insulin clearance in obese populations. OBJECTIVE: To examine the
      cross-sectional relationship between insulin clearance and resting sympathetic
      nervous system activity in a cohort of obese subjects with metabolic syndrome.
      PARTICIPANTS AND METHODS: Unmedicated, nonsmoking subjects (31 male, 27 female;
      aged 56 +/- 1 year; body mass index 33.7 +/- 0.6 kg/m(2)) underwent euglycemic
      hyperinsulinemic clamp to determine insulin sensitivity (M) and insulin
      clearance, assessment of norepinephrine kinetics, peripheral arterial tonometry,
      Doppler echocardiography, and oral glucose tolerance test. RESULTS: Univariate
      correlation analyses showed inverse associations between insulin clearance and
      arterial norepinephrine concentration (r = -0.44, P = .0006), calculated
      norepinephrine spillover rate (r = -0.33, P = .01), augmentation index (AI, r = 
      0.37, P = .005), and positive associations with M (r = 0.30, P = .02), Matsuda
      insulin sensitivity index (r = 0.27, P = .04), and cardiac output (r = 0.27, P =
      .04). Insulin clearance and sensitivity did not differ between genders, however
      females had higher AI compared to males (35 +/- 3% versus 14 +/- 2%, P < .001).
      In age and gender adjusted stepwise regression analyses, arterial norepinephrine
      concentration alone explained 19% of the variance in insulin clearance. When all
      significant variables were entered into the regression model, arterial
      norepinephrine, AI, gender, and M were independent predictors of insulin
      clearance, together explaining 41% of the variance. CONCLUSIONS: Arterial
      norepinephrine concentration is inversely and independently associated with whole
      body insulin clearance rate in obese individuals with metabolic syndrome.
      Prospective studies are needed to determine the direction of causality and the
      chronology of interactions between insulin clearance and sympathetic neural
      activity.

PMID- 25590213
TI  - Clinical review: Drugs commonly associated with weight change: a systematic
      review and meta-analysis.
AB  - CONTEXT: Various drugs affect body weight as a side effect. OBJECTIVE: We
      conducted this systematic review and meta-analysis to summarize the evidence
      about commonly prescribed drugs and their association with weight change. DATA
      SOURCES: MEDLINE, DARE, and the Cochrane Database of Systematic Reviews were
      searched to identify published systematic reviews as a source for trials. STUDY
      SELECTION: We included randomized trials that compared an a priori selected list
      of drugs to placebo and measured weight change. DATA EXTRACTION: We extracted
      data in duplicate and assessed the methodological quality using the Cochrane risk
      of bias tool. RESULTS: We included 257 randomized trials (54 different drugs; 84
      696 patients enrolled). Weight gain was associated with the use of amitriptyline
      (1.8 kg), mirtazapine (1.5 kg), olanzapine (2.4 kg), quetiapine (1.1 kg),
      risperidone (0.8 kg), gabapentin (2.2 kg), tolbutamide (2.8 kg), pioglitazone
      (2.6 kg), glimepiride (2.1 kg), gliclazide (1.8 kg), glyburide (2.6 kg),
      glipizide (2.2 kg), sitagliptin (0.55 kg), and nateglinide (0.3 kg). Weight loss
      was associated with the use of metformin (1.1 kg), acarbose (0.4 kg), miglitol
      (0.7 kg), pramlintide (2.3 kg), liraglutide (1.7 kg), exenatide (1.2 kg),
      zonisamide (7.7 kg), topiramate (3.8 kg), bupropion (1.3 kg), and fluoxetine (1.3
      kg). For many other remaining drugs (including antihypertensives and
      antihistamines), the weight change was either statistically nonsignificant or
      supported by very low-quality evidence. CONCLUSIONS: Several drugs are associated
      with weight change of varying magnitude. Data are provided to guide the choice of
      drug when several options exist and institute preemptive weight loss strategies
      when obesogenic drugs are prescribed.

PMID- 25590216
TI  - Percutaneous autologous pancreatic islet cell transplantation for traumatic
      pancreatic injury.
AB  - CONTEXT: Traumatic pancreatic injury with pancreatic duct disruption is
      surgically managed with at least a partial pancreatectomy, often leading to poor
      blood glucose control and the subsequent development of diabetes mellitus.
      Autologous beta-islet cell transplantation may therefore help to preserve
      pancreatic endocrine function. CASE DESCRIPTION: We describe 3 patients with
      pancreatic duct disruption from traumatic pancreatic injury who were treated with
      a partial pancreatectomy followed by autologous beta-islet cell transplantation
      via a percutaneous transhepatic approach. Immediately after trauma, 2 of the 3
      patients had difficulty with glucose control that resolved after autologous beta
      islet cell transplantation. At follow-up, all patients remained normoglycemic.
      CONCLUSION: In patients requiring partial pancreatectomy after pancreatic trauma,
      percutaneous transhepatic autologous beta-islet cell transplantation should be
      considered to minimize the risk of development of diabetes mellitus.

PMID- 25590215
TI  - Prophylactic central compartment lymph node dissection in papillary thyroid
      carcinoma: clinical implications derived from the first prospective randomized
      controlled single institution study.
AB  - BACKGROUND: The benefits of prophylactic central compartment lymph node
      dissection (pCCND) in papillary thyroid cancer (PTC) are still under
      investigation. This treatment seems to reduce PTC recurrence/mortality rates but
      has a higher risk of surgical complications. The lack of prospective randomized
      trials does not allow definitive recommendations. The aim of this prospective
      randomized controlled study was to evaluate the clinical advantages and
      disadvantages of pCCND. PATIENTS: A total of 181 patients with PTC without
      evidence of preoperative/intraoperative lymph node metastases (cN0) were randomly
      assigned to either Group A (n = 88) and treated with total thyroidectomy (TTx) or
      Group B (n = 93) and treated with TTx + pCCND. RESULTS: After 5 years of
      followup, no difference was observed in the outcome of the two groups. However, a
      higher percentage of Group A were treated with a higher number of (131)I courses
      (P = .002), whereas a higher prevalence of permanent hypoparathyroidism was
      observed in Group B (P = .02). No preoperative predictors of central compartment
      lymph node metastases (N1a) were identified. Only three patients were upstaged,
      and the therapeutic strategy changed in only one case. CONCLUSIONS: cN0 patients
      with PTC treated either with TTx or TTx + pCCND showed a similar outcome. One
      advantage of TTx + pCCND was a reduced necessity to repeat (131)I treatments, but
      the disadvantage was a higher prevalence of permanent hypoparathyroidism. Almost
      50% of patients with PTC had micrometastatic lymph nodes in the central
      compartment, but none of the presurgical features analyzed, including BRAF
      mutation, was able to predict their presence; moreover, to be aware of their
      presence does not seem to have any effect on the outcome.

PMID- 25590217
TI  - In postmenopausal female subjects with type 2 diabetes mellitus, vertebral
      fractures are independently associated with cortisol secretion and sensitivity.
AB  - CONTEXT: In type 2 diabetes (T2D), the vertebral fracture (VFx) prevalence and
      cortisol secretion are increased. OBJECTIVE: The objective of this study was to
      evaluate the role of glucocorticoid secretion and sensitivity in T2D-related
      osteoporosis. DESIGN AND SETTING: This was a case-control study in an outpatient
      setting. PATIENTS: The patients were ninety-nine well-compensated T2D
      postmenopausal women (age, 65.7 +/- 7.3 y) and 107 controls (age, 64.5 +/- 8.2
      y). MAIN OUTCOME MEASURES: We assessed osteocalcin, C-terminal telopeptide of
      type I collagen, ACTH, cortisol after the dexamethasone suppression test (F
      1mgDST), BclI and N363S single-nucleotide polymorphisms (SNPs) of glucocorticoid
      receptor, lumbar spine and femoral neck bone mineral density by dual x-ray
      absorptiometry, and VFx by radiography. RESULTS: Compared with controls, T2D
      subjects had increased VFx prevalence (20 vs 34.3%, respectively; P = .031), bone
      mineral density (Z-scores, lumbar spine, 0.16 +/- 1.28 vs 0.78 +/- 1.43, P =
      .001; femoral neck, -0.03 +/- 0.87 vs 0.32 +/- 0.98, P = .008, respectively), and
      F-1mgDST (1.06 +/- 0.42 vs 1.21 +/- 0.44 MUg/dL, 29.2 +/- 1.2 vs 33.3 +/- 1.2
      nmol/L, respectively; P = .01), and decreased osteocalcin (10.6 +/- 6.4 vs 4.9 +/
      3.2 ng/mL, 10.6 +/- 6.4 vs 4.9 +/- 3.2 MUg/L, respectively; P < .0001) and C
      terminal telopeptide of type I collagen (0.28 +/- 0.12 vs 0.14 +/- 0.08 ng/mL,
      0.28 +/- 0.12 vs 0.14 +/- 0.08 mcg/L, respectively; P < .0001). Fractured
      controls or T2D patients had increased sensitizing N363S SNP prevalence (20 and
      17.6%, respectively) compared to non-fractured subjects (3.4 and 3.1%,
      respectively; P = .02 for both comparisons), and similar BclI SNP prevalence. The
      VFx presence was associated with the sensitizing variant of N363S SNPs in
      controls (odds ratio [OR] = 10.6; 95% confidence interval [CI], 1.8-63.3; P =
      .01) and in T2D patients (OR = 12.5; 95% CI, 1.8-88.7; P = .01), and with the F
      1mgDST levels (OR = 2.1; 95% CI, 1.1-4.1; P = .03) only in T2D patients.
      CONCLUSIONS: In postmenopausal T2D women, VFx are associated with cortisol
      secretion and the sensitizing variant of N363S SNPs.

PMID- 25590218
TI  - The smallest of the small: short-term outcomes of profoundly growth restricted
      and profoundly low birth weight preterm infants.
AB  - OBJECTIVE: Survival of preterm and very low birth weight (VLBW) infants has
      steadily improved. However, the rates of mortality and morbidity among the very
      smallest infants are poorly characterized. STUDY DESIGN: Data from the California
      Perinatal Quality Care Collaborative for the years 2005 to 2012 were used to
      compare the mortality and morbidity of profoundly low birth weight (ProLBW, birth
      weight 300 to 500 g) and profoundly small for gestational age (ProSGA, <1st
      centile for weight-for-age) infants with very low birth weight (VLBW, birth
      weight 500 to 1500 g) and appropriate for gestational age (AGA, 5th to 95th
      centile for weight-for-age) infants, respectively. RESULT: Data were available
      for 44 561 neonates of birth weight <1500 g. Of these, 1824 were ProLBW and 648
      were ProSGA. ProLBW and ProSGA differed in their antenatal risk factors from the
      comparison groups and were less likely to receive antenatal steroids or to be
      delivered by cesarean section. Only 14% of ProSGA and 21% of ProLBW infants
      survived to hospital discharge, compared with >80% of AGA and VLBW infants. The
      largest increase in mortality in ProSGA and ProLBW infants occurred prior to 12 h
      of age, and most mortality happened in this time period. Survival of the ProLBW
      and ProSGA infants was positively associated with higher gestational age, receipt
      of antenatal steroids, cesarean section delivery and singleton birth. CONCLUSION:
      Survival of ProLBW and ProSGA infants is uncommon, and survival without
      substantial morbidity is rare. Survival is positively associated with receipt of
      antenatal steroids and cesarean delivery.

PMID- 25590219
TI  - Prone positioning decreases cardiac output and increases systemic vascular
      resistance in neonates.
AB  - OBJECTIVE: To evaluate the cardiovascular response to short-term prone
      positioning in neonates. STUDY DESIGN: In this prospective study, we continuously
      monitored heart rate (HR), stroke volume (SV) and cardiac output (CO) by
      electrical velocimetry in hemodynamically stable neonates in each of the
      following positions for 10 min: supine, prone and back-to-supine position. Skin
      blood flow (SBF) was also continuously assessed on the forehead or foot using
      Laser Doppler technology. Systemic vascular resistance (SVR) index was calculated
      as mean blood pressure (BP)/CO. Data were analyzed using repeated measures
      analysis of variance. RESULTS: Thirty neonates (gestational age: 35+/-4 weeks;
      postmenstrual age: 36+/-3 weeks) were enrolled. HR did not change in response to
      positioning. However, in prone position, SV, CO and SBF decreased and SVR index
      increased from 1.5+/-0.3 to 1.3+/-0.3 ml kg(-1) (mean +/-s.d., P<0.01), 206+/-44
      to 180+/-41 ml kg(-1) min(-1) (P<0.01), 0.54+/-0.30 to 0.44+/-0.29 perfusion
      units (P<0.01) and 0.25+/-0.06 to 0.30+/-0.07 mm Hg ml(-1) kg(-1) min(-1)
      (P<0.01), respectively. After placing the infants back-to-supine position, SV,
      CO, SBF and SVR index returned to baseline. The above pattern of cardiovascular
      changes was consistent in vast majority of the studied neonates. CONCLUSIONS:
      Short-term prone positioning is associated with decreased SV, CO and SBF and
      increased calculated SVR index.

PMID- 25590220
TI  - Nutritional outcomes with implementation of probiotics in preterm infants.
AB  - OBJECTIVE: To assess nutritional outcomes in preterm infants after the
      implementation of probiotics. STUDY DESIGN: Retrospective chart review of infants
      with birth weight?1250 grams and/or?28 weeks of gestational age admitted to the
      KCH-Neonatal Intensive Care Unit was done. Data were collected over two periods,
      period 1 (before probiotics) and period 2 (after probiotics) and included
      demographic data, daily weight gain, feeding strategies (type, amount, caloric
      content and frequency of feeds) and comorbidities affecting feedings (Patent
      ductus arteriosus, Sepsis). Primary outcomes-extra uterine growth restriction
      (EUGR) status and incidence of necrotizing enterocolitis (NEC) as well as
      secondary outcomes-time to reach full feeds, feeding intolerance episodes and
      weight gain were compared between the two groups. RESULTS: A total of 113 infants
      (period 1) were compared with 108 infants (period 2). The odds of EUGR was
      significantly lower with probiotics (odds ratio: 0.3, 95% confidence interval
      0.138 to 0.611). Time to reach full feeds was significantly reduced and weight
      gain was significantly better in period 2. Significant reduction was also noted
      in number of total parental nutrition days, central line days, nil per os days
      and number of feeding intolerance episodes in period 2. There was no significant
      difference in the incidence of NEC. CONCLUSION: Probiotics improve feeding
      tolerance leading to better overall growth and decreases the incidence of EUGR in
      preterm infants.

PMID- 25590222
TI  - Correction to "What a Difference a Decade Has Not Made: The Murky Electronic
      Structure of Iron Monocyanide (FeCN) and Iron Monoisocyanide (FeNC)".

PMID- 25590221
TI  - Relationship of maternal creatinine to first neonatal creatinine in infants <30
      weeks gestation.
AB  - OBJECTIVE: To examine the relationship between maternal and neonatal creatinine
      (Cr) in preterm infants in the context of antenatal and intrapartum maternal and
      neonatal factors. STUDY DESIGN: In this 51/2-year, single-center, retrospective
      study, paired maternal and neonatal Cr were compared by t-test. Linear regression
      for correlated outcomes employing generalized estimating equations was used to
      examine neonatal Cr as a function of antenatal maternal Cr and potential
      confounders. RESULT: A total of 157 neonates of 124 mothers met study criteria.
      Neonatal Cr values in the first 24 h of life were significantly higher than
      antenatal maternal values. Linear regression modeling showed that maternal Cr,
      neonatal lactate, hypoxic-ischemic villous changes on placental pathology and
      multiple gestation were each significant determinants of the first neonatal Cr.
      CONCLUSION: No neonatal Cr was less than its paired maternal value. Maternal Cr,
      neonatal lactate, hypoxic-ischemic villous changes in the placenta and multiple
      gestation were each significantly associated with neonatal Cr.

PMID- 25590225
TI  - Contrasting performance of donor-acceptor copolymer pairs in ternary blend solar
      cells and two-acceptor copolymers in binary blend solar cells.
AB  - Here two contrasting approaches to polymer-fullerene solar cells are compared. In
      the first approach, two distinct semi-random donor-acceptor copolymers are
      blended with phenyl-C61-butyric acid methyl ester (PC61BM) to form ternary blend
      solar cells. The two poly(3-hexylthiophene)-based polymers contain either the
      acceptor thienopyrroledione (TPD) or diketopyrrolopyrrole (DPP). In the second
      approach, semi-random donor-acceptor copolymers containing both TPD and DPP
      acceptors in the same polymer backbone, termed two-acceptor polymers, are blended
      with PC61BM to give binary blend solar cells. The two approaches result in bulk
      heterojunction solar cells that have the same molecular active-layer components
      but differ in the manner in which these molecular components are mixed, either by
      physical mixing (ternary blend) or chemical "mixing" in the two-acceptor (binary
      blend) case. Optical properties and photon-to-electron conversion efficiencies of
      the binary and ternary blends were found to have similar features and were
      described as a linear combination of the individual components. At the same time,
      significant differences were observed in the open-circuit voltage (Voc) behaviors
      of binary and ternary blend solar cells. While in case of two-acceptor polymers,
      the Voc was found to be in the range of 0.495-0.552 V, ternary blend solar cells
      showed behavior inherent to organic alloy formation, displaying an intermediate,
      composition-dependent and tunable Voc in the range from 0.582 to 0.684 V,
      significantly exceeding the values achieved in the two-acceptor containing binary
      blend solar cells. Despite the differences between the physical and chemical
      mixing approaches, both pathways provided solar cells with similar power
      conversion efficiencies, highlighting the advantages of both pathways toward
      highly efficient organic solar cells. 

PMID- 25590223
TI  - Phaeohyphomycosis caused by Exophiala spinifera: an increasing disease in young
      females in mainland China? Two case reports and review of five cases reported
      from mainland China.
AB  - No more than 30 cases of phaeohyphomycosis caused by Exophiala spinifera have
      been reported up to now in English and Chinese literature over the past half
      century. Here, we reported two cases of phaeohyphomycosis caused by E. spinifera
      and reviewed all the five cases reported from mainland China. These two involved
      were both young female, one patient experiencing recurrence during pregnancy and
      the other developing multiple-site infections without apparent immunodeficiency.
      The aetiological agents were both identified as E. spinifera by molecular
      analysis. Oral itraconazole was proved effective enough for the first patient,
      while the combination of itraconazole and terbinafine was needed for the second
      patient. It seems that infections due to E. spiniferais increasing in China
      mainland nowadays, usually involving young female.

PMID- 25590224
TI  - Let there be light: regulation of gene expression in plants.
AB  - Gene expression regulation relies on a variety of molecular mechanisms affecting
      different steps of a messenger RNA (mRNA) life: transcription, processing,
      splicing, alternative splicing, transport, translation, storage and decay. Light
      induces massive reprogramming of gene expression in plants. Differences in
      alternative splicing patterns in response to environmental stimuli suggest that
      alternative splicing plays an important role in plant adaptation to changing life
      conditions. In a recent publication, our laboratories showed that light regulates
      alternative splicing of a subset of Arabidopsis genes encoding proteins involved
      in RNA processing by chloroplast retrograde signals. The light effect on
      alternative splicing is also observed in roots when the communication with the
      photosynthetic tissues is not interrupted, suggesting that a signaling molecule
      travels through the plant. These results point at alternative splicing regulation
      by retrograde signals as an important mechanism for plant adaptation to their
      environment. 

PMID- 25590226
TI  - Subcloning plus insertion (SPI)--a novel recombineering method for the rapid
      construction of gene targeting vectors.
AB  - Gene targeting refers to the precise modification of a genetic locus using
      homologous recombination. The generation of novel cell lines and transgenic mouse
      models using this method necessitates the construction of a 'targeting' vector,
      which contains homologous DNA sequences to the target gene, and has for many
      years been a limiting step in the process. Vector construction can be performed
      in vivo in Escherichia coli cells using homologous recombination mediated by
      phage recombinases using a technique termed recombineering. Recombineering is the
      preferred technique to subclone the long homology sequences (>4 kb) and various
      targeting elements including selection markers that are required to mediate
      efficient allelic exchange between a targeting vector and its cognate genomic
      locus. Typical recombineering protocols follow an iterative scheme of step-wise
      integration of the targeting elements and require intermediate purification and
      transformation steps. Here, we present a novel recombineering methodology of
      vector assembly using a multiplex approach. Plasmid gap repair is performed by
      the simultaneous capture of genomic sequence from mouse Bacterial Artificial
      Chromosome libraries and the insertion of dual bacterial and mammalian selection
      markers. This subcloning plus insertion method is highly efficient and yields a
      majority of correct recombinants. We present data for the construction of
      different types of conditional gene knockout, or knock-in, vectors and BAC
      reporter vectors that have been constructed using this method. SPI vector
      construction greatly extends the repertoire of the recombineering toolbox and
      provides a simple, rapid and cost-effective method of constructing these highly
      complex vectors.

PMID- 25590227
TI  - From a cracking facade to a total escape: maladaptive perfectionism and suicide.
AB  - This study explored the final stages of the suicide process among six men
      characterized as maladaptive perfectionists. These men, aged 22 to 58, had no
      history of suicide attempts or mental health treatment. In-depth interviews with
      5 to 9 informants for each person were analyzed by using interpretative
      phenomenological analysis. Three themes emerged from the analysis: (a) a cracking
      facade; (b) a total loss of coping ability; and (c) a total escape. Suicide was
      related to a shameful defeat that was not reversible, and a loss of the ability
      to handle such feelings of defeat and shame. 

PMID- 25590228
TI  - Trichosporon asahii infection presenting as chronic meningo-ventriculitis and
      intra ventricular fungal ball: a case report and literature review.
AB  - Central nervous system trichosporonosis is a rare clinical entity and so far only
      six cases including three each of brain abscess and meningitis has been on
      record. We report a rare case of chronic meningo-ventriculitis and
      intraventricular fungal ball due to Trichosporon asahii in an 18-year-old
      immunocompetent male from Burundi, east Africa. Neuroendoscopy showed multiple
      nodules and a fungal ball within the ventricle, which on culture grew T. asahii.
      He was initially empirically treated with liposomal amphotericin B. However, the
      antifungal susceptibility testing of T. asahii isolate revealed high minimum
      inhibitory concentration for amphotericin B (2 MUg ml-1), flucytosine (16 MUg ml
      1) and caspofungin (2 MUg ml-1) but exhibited potent activity for voriconazole,
      posaconazole, itraconazole and fluconazole. The patient rapidly succumbed to
      cardiac arrest before antifungal therapy could be changed. Although disseminated
      trichosporonosis has been increasingly reported the diagnosis represents a
      challenge especially in rare clinical settings such as intraventricular fungal
      ball in the present case, which has not been described previously.

PMID- 25590229
TI  - Radiation-induced second primary cancer risks from modern external beam
      radiotherapy for early prostate cancer: impact of stereotactic ablative
      radiotherapy (SABR), volumetric modulated arc therapy (VMAT) and flattening
      filter free (FFF) radiotherapy.
AB  - Risks of radiation-induced second primary cancer following prostate radiotherapy
      using 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy
      (IMRT), volumetric modulated arc therapy (VMAT), flattening filter free (FFF) and
      stereotactic ablative radiotherapy (SABR) were evaluated. Prostate plans were
      created using 10 MV 3D-CRT (78 Gy in 39 fractions) and 6 MV 5-field IMRT (78 Gy
      in 39 fractions), VMAT (78 Gy in 39 fractions, with standard flattened and energy
      matched FFF beams) and SABR (42.7 Gy in 7 fractions with standard flattened and
      energy-matched FFF beams). Dose-volume histograms from pelvic planning CT scans
      of three prostate patients, each planned using all 6 techniques, were used to
      calculate organ equivalent doses (OED) and excess absolute risks (EAR) of second
      rectal and bladder cancers, and pelvic bone and soft tissue sarcomas, using
      mechanistic, bell-shaped and plateau models. For organs distant to the treatment
      field, chamber measurements recorded in an anthropomorphic phantom were used to
      calculate OEDs and EARs using a linear model. Ratios of OED give relative
      radiation-induced second cancer risks. SABR resulted in lower second cancer risks
      at all sites relative to 3D-CRT. FFF resulted in lower second cancer risks in out
      of-field tissues relative to equivalent flattened techniques, with increasing
      impact in organs at greater distances from the field. For example, FFF reduced
      second cancer risk by up to 20% in the stomach and up to 56% in the brain,
      relative to the equivalent flattened technique. Relative to 10 MV 3D-CRT, 6 MV
      IMRT or VMAT with flattening filter increased second cancer risks in several out
      of-field organs, by up to 26% and 55%, respectively. For all techniques, EARs
      were consistently low. The observed large relative differences between
      techniques, in absolute terms, were very low, highlighting the importance of
      considering absolute risks alongside the corresponding relative risks, since when
      absolute risks are very low, large relative risks become less meaningful. A
      calculated relative radiation-induced second cancer risk benefit from SABR and
      FFF techniques was theoretically predicted, although absolute radiation-induced
      second cancer risks were low for all techniques, and absolute differences between
      techniques were small.

PMID- 25590230
TI  - Activation of cellular apoptosis in the caecal epithelium is associated with
      increased oxidative reactions in lactating goats after feeding a high-concentrate
      diet.
AB  - NEW FINDINGS: What is the central question of this study? What are the
      ultrastructural changes of the caecal mucosa and the status of epithelial
      cellular apoptosis and oxidative reactions in lactating goats after prolonged
      feeding with a high-concentrate diet? What is the main finding and its
      importance? High-concentrate diet results in ultrastructural damage to the
      caprine caecal epithelium. Increased oxidative and decreased antioxidative
      reactions are involved in the process of activating epithelial apoptosis in the
      caecal epithelium of goats fed a high-concentrate diet. Our results provide new
      insight into the relationship between abnormal fermentation in the hindgut and
      damage to the intestinal mucosal barrier. The effect of feeding a high
      concentrate diet (HC) to lactating ruminants on their hindgut epithelial
      structure remains unknown. In this study, 12 lactating goats were randomly
      assigned to either HC (65% of dry matter as concentrate; n = 6) or a low
      concentrate diet (LC; 35% of dry matter as concentrate; n = 6). After 10 weeks,
      the epithelial ultrastructure and cell apoptotic status in the caecal mucosa were
      determined by transmission electron microscopy and TUNEL, respectively. The
      results showed that the level of free lipopolysaccharide (P < 0.05), total
      volatile fatty acid concentrations (P < 0.1) and starch content (P < 0.05) in the
      caecal digesta were significantly increased in HC- compared with LC-fed goats.
      The HC-fed goats exhibited obvious epithelial cellular damage, with widened tight
      junction spaces, nuclear breakdown and mitochondrial swelling. Compared with
      their LC-fed counterparts, HC-fed goats showed greater apoptosis in the caecal
      epithelium, as evidenced by more TUNEL-positive apoptotic cells. Western blot
      analysis showed that there was no significant difference in activated caspase-3,
      Bax protein expression in caecal epithelial mucosa between HC- and LC-fed goats
      (P > 0.05). However, the level of malondialdehyde content in the caecal
      epithelium from HC-fed goats was markedly higher than that in LC-fed goats (P <
      0.05), whereas the level of glutathione peroxidase and the superoxide dismutase
      activity were significantly decreased. Gene expressions of cytokines, including
      interleukin-1beta, interleukin-6, interleukin-10, tumour necrosis factor-alpha
      and interferon-gamma, as well as myeloperoxidase activity in the caecal mucosa
      did not show any significant difference between HC- and LC-fed goats. These
      results indicate that feeding a high-concentrate diet to lactating goats for a
      prolonged period results in abnormal fermentation and structural disruption in
      the hindgut, which is accompanied by greater cellular apoptosis and an enhanced
      oxidative stress response.

PMID- 25590231
TI  - The neuromuscular junction: measuring synapse size, fragmentation and changes in
      synaptic protein density using confocal fluorescence microscopy.
AB  - The neuromuscular junction (NMJ) is the large, cholinergic relay synapse through
      which mammalian motor neurons control voluntary muscle contraction. Structural
      changes at the NMJ can result in neurotransmission failure, resulting in
      weakness, atrophy and even death of the muscle fiber. Many studies have
      investigated how genetic modifications or disease can alter the structure of the
      mouse NMJ. Unfortunately, it can be difficult to directly compare findings from
      these studies because they often employed different parameters and analytical
      methods. Three protocols are described here. The first uses maximum intensity
      projection confocal images to measure the area of acetylcholine receptor (AChR)
      rich postsynaptic membrane domains at the endplate and the area of synaptic
      vesicle staining in the overlying presynaptic nerve terminal. The second protocol
      compares the relative intensities of immunostaining for synaptic proteins in the
      postsynaptic membrane. The third protocol uses Fluorescence Resonance Energy
      Transfer (FRET) to detect changes in the packing of postsynaptic AChRs at the
      endplate. The protocols have been developed and refined over a series of studies.
      Factors that influence the quality and consistency of results are discussed and
      normative data are provided for NMJs in healthy young adult mice. 

PMID- 25590235
TI  - Profiling the preterm or VLBW born adolescent; implications of the Dutch POPS
      cohort follow-up studies.
AB  - In 1983, data of a unique nationwide cohort of 1338 very preterm (<32 weeks of
      gestation) or VLBW (birth weight<1500g) infants in the Netherlands was collected
      and followed at several ages until they reached the age of 19 years. At 19 years
      of age a more extensive follow-up study was done, including questionnaires, tests
      on a computer and a full physical exam. These studies provide insight into how
      Dutch adolescents at 19 years of age, who were born very preterm or with a very
      low birth weight (VLBW), reach adulthood. At 19 years, 705 POPS participants
      participated (74% of 959 still alive). Outcome measures at 19 years included:
      physical outcomes (e.g. blood pressure), cognition, behavior, quality of life,
      and impact of handicaps. The POPS participants showed more impairments on most
      outcome measures at various ages, compared to norm data. Major handicaps remained
      stable as the children grew older, but minor handicaps and disabilities
      increased. At 19 years of age, only half (47.1%) of the survivors had no
      disabilities and no minor or major handicaps. Especially those born small for
      gestational age (SGA) seem most vulnerable. These long-term results help to
      support preterm and SGA born children and adolescents in reaching independent
      adulthood, and stress the need for long term follow-up studies and to promote
      prevention of disabilities and of preterm birth itself.

PMID- 25590236
TI  - Precious life-blood of a master-spirit.
AB  - Recent books on microscopy and related topics, including bad writing, are
      examined. 

PMID- 25590237
TI  - Representation of Disease: What's in a Name?

PMID- 25590233
TI  - New strategy for in vitro activation of primordial follicles with mTOR and PI3K
      stimulators.
AB  - It had been known for decades that primordial follicles in mammalian ovaries are
      assembled with definite numbers and represent the ovarian reserve throughout the
      reproductive life. Intra-oocyte PI3K/mTOR pathways have been indicated to play a
      central role on the activation of primordial follicles. Genetic modified mouse
      models with chronic activation of PI3K/mTOR signals in primordial oocytes showed
      premature activation of all primordial follicles and eventually their exhaustion.
      On the other hand, this may suggest that, unlike chronic activation of PI3K/mTOR,
      its acute activation in infertility would activate primordial follicles,
      permitting fertility during the treatment. Previously, PI3K stimulators were
      reported as a temporary measure to accelerate primordial follicle activation and
      follicular development in both mouse and human, and were applied in the treatment
      of infertility in premature ovarian failure (POF) patients. To address whether
      mTOR stimulators could play similar role in the process, we transiently treated
      neonatal and aged mouse ovaries with mTOR stimulators-phosphatidic acid (PA) and
      propranolol. Our results demonstrated the stimulators increased activation of
      primordial follicles and the production of progeny. Human ovarian cortex cubes
      were also treated with mTOR or/and PI3K stimulators in vitro. When they were used
      separately, both of them showed similar promotive effects on primordial
      follicles. Surprisingly, after joint-treatment with the 2 kinds of stimulators
      together, synergistic effects on follicular development were observed. Based on
      increased efficiency of follicular activation in humans, here we propose in vitro
      transient treatment with mTOR and PI3K stimulators as an optimized protocol for
      the application in different clinical conditions with limited follicle reserve. 

PMID- 25590232
TI  - NK cell-based immunotherapies in Pediatric Oncology.
AB  - The past decade has seen several anticancer immunotherapeutic strategies
      transition from "promising preclinical models" to treatments with proven clinical
      activity or benefit. In 2013, the journal Science selected the field of Cancer
      Immunotherapy as the overall number-1 breakthrough for the year in all of
      scientific research. In the setting of cancer immunotherapy for adult
      malignancies, many of these immunotherapy strategies have relied on the cancer
      patient's endogenous antitumor T-cell response. Although much promising research
      in pediatric oncology is similarly focused on T-cell reactivity, several
      pediatric malignancies themselves, or the chemo-radiotherapy used to achieve
      initial responses, can be associated with profound immune suppression,
      particularly of the T-cell system. A separate component of the immune system,
      also able to mediate antitumor effects and less suppressed by conventional cancer
      treatment, is the NK-cell system. In recent years, several distinct
      immunotherapeutic approaches that rely on the activity of NK cells have moved
      from preclinical development into clinical testing, and some have shown clear
      antitumor benefit. This review provides an overview of NK cell-based
      immunotherapy efforts that are directed toward childhood malignancies, with an
      emphasis on protocols that are already in clinical testing. 

PMID- 25590238
TI  - Polyacrylamide gels for invadopodia and traction force assays on cancer cells.
AB  - Rigid tumor tissues have been strongly implicated in regulating cancer cell
      migration and invasion. Invasive migration through cross-linked tissues is
      facilitated by actin-rich protrusions called invadopodia that proteolytically
      degrade the extracellular matrix (ECM). Invadopodia activity has been shown to be
      dependent on ECM rigidity and cancer cell contractile forces suggesting that
      rigidity signals can regulate these subcellular structures through actomyosin
      contractility. Invasive and contractile properties of cancer cells can be
      correlated in vitro using invadopodia and traction force assays based on
      polyacrylamide gels (PAAs) of different rigidities. Invasive and contractile
      properties of cancer cells can be correlated in vitro using invadopodia and
      traction force assays based on polyacrylamide gels (PAAs) of different
      rigidities. While some variations between the two assays exist, the protocol
      presented here provides a method for creating PAAs that can be used in both
      assays and are easily adaptable to the user's specific biological and technical
      needs. 

PMID- 25590239
TI  - Photochemical nitrogen conversion to ammonia in ambient conditions with FeMoS
      chalcogels.
AB  - In nature, nitrogen fixation is one of the most important life processes and
      occurs primarily in microbial organisms containing enzymes called nitrogenases.
      These complex proteins contain two distinct subunits with different active sites,
      with the primary N2 binding site being a FeMoS core cluster that can be reduced
      by other nearby iron-sulfur clusters. Although nitrogen reduction to ammonia in
      biology does not require the absorption of light, there is considerable interest
      in developing catalyst materials that could drive the formation of ammonia from
      nitrogen photochemically. Here, we report that chalcogels containing FeMoS
      inorganic clusters are capable of photochemically reducing N2 to NH3 under white
      light irradiation, in aqueous media, under ambient pressure and room temperature.
      The chalcogels are composed of [Mo2Fe6S8(SPh)3](3+) and [Sn2S6](4-) clusters in
      solution and have strong optical absorption, high surface area, and good aqueous
      stability. Our results demonstrate that light-driven nitrogen conversion to
      ammonia by MoFe sulfides is a viable process with implications in solar energy
      utilization and our understanding of primordial processes on earth. 

PMID- 25590241
TI  - Rapid discrimination and feature extraction of three Chamaecyparis species by
      static-HS/GC-MS.
AB  - This study aimed to develop a rapid and accurate analytical method for
      discriminating three Chamaecyparis species (C. formosensis, C. obtusa, and C.
      obtusa var. formosana) that could not be easily distinguished by volatile
      compounds. A total of 23 leaf samples from three species were analyzed by static
      headspace (static-HS) coupled with gas chromatography-mass spectrometry (GC-MS).
      The static-HS procedure, whose experimental parameters were properly optimized,
      yielded a high Pearson correlation-based similarity between essential oil and VOC
      composition (r = 0.555-0.999). Thirty-six major constituents were identified;
      along with the results of cluster analysis (CA), a large variation in contents
      among the three different species was observed. Principal component analysis
      (PCA) methods illustrated graphically the relationships between characteristic
      components and tree species. It was clearly demonstrated that the static-HS-based
      procedure enhanced greatly the speed of precise analysis of chemical fingerprint
      in small sample amounts, thus providing a fast and reliable tool for the
      prediction of constituent characteristics in essential oil, and also offering
      good opportunities for studying the role of these feature compounds in
      chemotaxonomy or ecophysiology. 

PMID- 25590240
TI  - PCDH10, a novel p53 transcriptional target in regulating cell migration.
AB  - Cell cycle arrest, senescence and apoptosis are commonly regarded as the major
      tumor suppression mechanisms of p53. However, accumulating evidence indicates
      that loss of these canonical functions is not sufficient for tumor formation,
      highlighting the complexity of p53-mediated tumor suppression. PCDH10 belongs to
      a proto cadherin protein family and is a potential tumor suppressor protein as
      the dysregulation of PCDH10 gene frequently existed in multiple human tumors.
      Here, we found that PCDH10 is a transcriptional target of p53 and that the levels
      of PCDH10 expression can be induced by wild type p53 but not mutant p53 in a
      number of human cancer cell lines. Moreover, we identified a p53 consensus
      binding site located in the PCDH10 promoter region that is responsive to p53
      regulation. Although upregulation of PCDH10 has no obvious effect on growth
      arrest or apoptosis in human cells, PCDH10 exhibits inhibitory roles in cancer
      cell motility and cell migration. These results suggest an important role of p53
      in regulating tumor cell migration through activating PCDH10 expression and
      support the notion that non-canonical activities of p53 may contribute to its
      tumor suppressor function in vivo.

PMID- 25590242
TI  - Maternal adiponectin controls milk composition to prevent neonatal inflammation.
AB  - Adiponectin is an important adipokine. Increasing evidence suggests that altered
      adiponectin levels are linked with metabolic and inflammatory disorders. Here we
      report an important yet previously unrecognized function of adiponectin in
      lactation by which maternal adiponectin determines the inflammatory status in the
      nursing neonates. Surprisingly, both maternal adiponectin overexpression in the
      transgenic mice and maternal adiponectin deletion in the knockout mice lead to
      systemic inflammation in the pups, manifested as transient hair loss. However,
      distinct mechanisms are involved. Adiponectin deficiency triggers leukocyte
      infiltration and production of inflammatory cytokines in the lactating mammary
      gland. In contrast, adiponectin overabundance increases lipid accumulation in the
      lactating mammary gland, resulting in excessive long-chain saturated fatty acids
      in milk. Interestingly, in both cases, the inflammation and alopecia in the pups
      can be rescued by Toll-like receptor (TLR)-2/4 deletion because TLR2/4 double
      knockout pups are resistant. Mechanistically, long-chain saturated fatty acid
      activation of inflammatory genes is TLR2/4 dependent and can be potentiated by
      proinflammatory cytokines, indicating that the inflammatory stimuli in both
      scenarios functionally converge by activating the TLR2/4 signaling. Therefore,
      our findings reveal adiponectin as a dosage-dependent regulator of lactation
      homeostasis and milk quality that critically controls inflammation in the nursing
      neonates. Furthermore, these results suggest that inflammatory infantile
      disorders may result from maternal adiponectin dysregulation that can be treated
      by TLR2/4 inhibition. 

PMID- 25590243
TI  - Metformin regulates ovarian angiogenesis and follicular development in a female
      polycystic ovary syndrome rat model.
AB  - Polycystic ovary syndrome (PCOS) is a frequent pathology that affects more than
      5% of women of reproductive age. Among other heterogeneous symptoms, PCOS is
      characterized by abnormalities in angiogenesis. Metformin has been introduced in
      the treatment of PCOS to manage insulin resistance and hyperglycemia. Besides its
      metabolic effects, metformin has been shown to improve ovulation, pregnancy and
      live birth rates in PCOS patients. In the present study, we used a
      dehydroepiandrosterone-induced PCOS rat model to analyze the effect of metformin
      administration on ovarian angiogenesis. We found that metformin was able to
      restore the increased levels of vascular endothelial growth factor, angiopoietin
      (ANGPT)1, and ANGPT1/ANGPT2 ratio and the decreased levels of platelet-derived
      growth factor B and platelet-derived growth factor D observed in the
      dehydroepiandrosterone-treated rats. These effects could take place, at least in
      part, through a decrease in the levels of serum insulin. We also found an
      improvement in follicular development, with a lower percentage of small follicles
      and cysts and a higher percentage of antral follicles and corpora lutea after
      metformin administration. The improvement in ovarian angiogenesis is likely to
      restore the accumulation of small follicles observed in PCOS rats and to reduce
      cyst formation, thus improving follicular development and the percentage of
      corpora lutea. These results open new insights into the study of metformin action
      not only in glucose metabolism but also in ovarian dysfunction in PCOS women. 

PMID- 25590245
TI  - Kisspeptin: beyond the brain.
AB  - The hypothalamic-based kisspeptin-signaling system is a major positive regulator
      of the neuroendocrine-reproductive axis in mammals. During the last decade, major
      advances have been made in understanding how this signaling system is regulated
      and how it can be manipulated clinically to achieve beneficial outcomes in
      treating sex steroid-dependent disorders. Interestingly, kisspeptin was not first
      identified as a regulator of fertility. Instead, approximately 7 years earlier
      KISS1 was reported to be expressed in nonmetastatic melanoma cells and was
      subsequently demonstrated to act as a powerful suppressor of the metastatic
      potential of malignant melanoma cells. Since this discovery, numerous studies
      have demonstrated the expression of the kisspeptin-signaling system at several
      peripheral sites implicating it in biological processes such as the regulation of
      ovarian function, embryo implantation, placentation, angiogenesis, insulin
      secretion, and kidney development. Although much work remains to be done to
      assess how important kisspeptin signaling is in regulating some of these
      processes, for other processes recent studies have made tremendous strides toward
      such an assessment. Using mice lacking either Kiss1 or Kiss1r alleles,
      researchers have provided compelling evidence for kisspeptin playing a major role
      in regulating breast cancer metastasis, oocyte survival, follicular maturation,
      ovulation, and embryo implantation. This review critically discusses the findings
      from these as well as other studies which suggest roles for kisspeptin in
      regulating important physiological processes beyond the brain. It also discusses
      the challenges that lie ahead in determining whether findings made with animal
      models are relevant in humans. 

PMID- 25590246
TI  - A classification system for fat necrosis in autologous breast reconstruction.

PMID- 25590247
TI  - Desferrioxamine: a practical method for improving neovascularization of
      prefabricated flaps.
AB  - BACKGROUND: Prefabricated flaps are an ideal alternative to repair massive and
      complex tissue defects. Nevertheless, the risk of necrosis due to unpredictable
      blood supplies is a major obstacle to the application of prefabricated flaps. The
      survival of a prefabricated flap depends on the neovascularization between the
      vascular carrier and the donor tissue. Here, we proposed that the iron chelator,
      desferrioxamine (DFX), owned therapeutic effects that promoted the
      neovascularization of prefabricated flaps. METHODS: An abdominal prefabricated
      flap model was created in rats via a 2-stage operation. The rats were allocated
      into 4 groups as follows: 2 groups of rats received DFX treatments during the
      first or the second stage of the operation, respectively; 1 group of rats
      received a delay procedure 1 week before the second operation; and the final
      group was used as a blank control. Flap survival rates and capillary densities
      were evaluated between groups. The influence of DFX on the dermal fibroblasts was
      also studied in vitro. RESULTS: Desferrioxamine treatment during the first stage
      of the operation greatly increased flap survival rate compared to the blank
      control. The results were similar to those produced by the delay treatment. The
      vessel count results were consistent with the flap survival rate findings. In
      vitro, DFX treatment up-regulated the expression levels of several angiogenic
      factors in the dermal fibroblasts. Nevertheless, DFX treatment during the second
      stage of the operation was therapeutically detrimental. CONCLUSIONS: The
      application of DFX around the time of vascular carrier implantation greatly
      promoted neovascularization of prefabricated flaps, but was therapeutically
      detrimental after the flaps had been elevated.

PMID- 25590244
TI  - Reduced melanocortin production causes sexual dysfunction in male mice with POMC
      neuronal insulin and leptin insensitivity.
AB  - Proopiomelanocortin (POMC)-derived peptides like alpha-melanocyte-stimulating
      hormone (MSH) substantially improve hepatic insulin sensitivity and regulate
      energy expenditure. Melanocortinergic agents are also powerful inducers of sexual
      arousal that are being investigated for a possible therapeutic role in erectile
      dysfunction. It is currently unclear whether reduced melanocortin (MC) activity
      may contribute to the sexual dysfunction accompanying obesity and type 2
      diabetes. Male rodents with leptin and insulin resistance targeted to POMC
      neurons (leptin receptor [LepR]/insulin receptor [IR]POMC mice) exhibit obesity,
      hyperinsulinemia, hyperglycemia, and systemic insulin resistance. In this study,
      we demonstrate that LepR/IRPOMC males are also subfertile due to dramatic
      alterations in sexual behavior. Remarkably, these reproductive changes are
      accompanied by decreased alpha-MSH production not present when a single receptor
      type is deleted. Unexpectedly, behavioral sensitivity to alpha-MSH and MC
      receptor expression are also reduced in LepR/IRPOMC males, a potential adaptation
      of the MC system to altered alpha-MSH production. Together, these results suggest
      that concurrent insulin and leptin resistance in POMC neurons in individuals with
      obesity or type 2 diabetes can reduce endogenous alpha-MSH levels and impair
      sexual function.

PMID- 25590248
TI  - Cost-benefit analysis of outcomes from the use of fibrin sealant for fixation of
      skin grafts in small-size burns compared to staples as historical controls: a
      retrospective review.
AB  - INTRODUCTION: Historically, split-thickness skin grafts have been fixed onto the
      recipient site by suture and/or staples. Fibrin sealants have become available
      for the fixation in the past 10 years. Fibrin sealants have been shown to be at
      least as effective as staples, and recent reports show them to cause less pain.
      However, the product is much more expensive than traditional suture and/or staple
      fixation. The cost-benefit ratio of sealant has not yet been proven. METHODS: A
      review of charts for 202 consecutive patients was undertaken for patients with
      burns that were less than 10% total body surface area (TBSA) that underwent
      excision and grafting using fibrin sealant at the regional burn center. A
      historical control comprising 48 consecutive patients with burns that were less
      than 10% TBSA that underwent excision and grafting using staples as the only
      means of fixation was used for comparison. Demographics (such as age, weight, and
      sex), personal history of tobacco use, previous diagnosis of diabetes, type and
      depth of burn, TBSA, area of grafting, graft and donor locations, mesh type, rate
      of hematomas, rate of graft loss, rate of complete closure at 1 month, and time
      to discharge after surgery were recorded for each patient in both cohorts. The
      data were compared and statistical analysis performed for graft loss
      complications and number of days until the patient could be discharged home with
      outpatient wound care. RESULTS: Use of fibrin sealants has resulted in
      statistically significant lower rates of loss of graft at our institution.
      Additionally, a decrease in the number of days until discharge to outpatient
      wound care of nearly 2 days produced a lower cost of care in patients with less
      than 10% TBSA undergoing excision and grafting. CONCLUSIONS: The use of fibrin
      sealants allows for fewer graft loss complications and earlier discharge in
      patients who have burns that are less than 10% TBSA. This decrease in hospital
      days results in savings, although this difference is not statistically
      significant.

PMID- 25590249
TI  - Local administration of beta-blockers for infantile hemangiomas: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Infantile hemangiomas (IHs) are a common pediatric lesion. Orally
      administered beta-blockers have been reported as effective in treating these
      lesions. However, oral administration is also associated with systemic adverse
      effects. Treatment with locally administered beta-blockers may provide acceptable
      efficacy with lower incidence of adverse effects. This may offer a better first
      line treatment. METHODS: PubMed was searched through March 2014 for studies
      reporting patient-level response of 5 or more patients treated with intralesional
      propranolol, topical timolol, or topical propranolol for cutaneous IHs. Rates of
      response to treatment, defined as clinically significant regression, were
      combined using random-effects meta-analysis. RESULTS: Ninety-four articles were
      identified. Seventeen articles met the study criteria. These studies primarily
      focused on superficial IHs. Response rates for topical propranolol and topical
      timolol were not significantly different, 76% [95% confidence interval (CI), 62%
      86%] and 83% (95% CI, 65%-93%), respectively (P=0.45). Prospectively conducted
      studies reported lower response rates compared to retrospective studies for both
      topical propranolol (P=0.06) and topical timolol (P<0.01). When only
      prospectively conducted studies were included, response rates for topical
      propranolol and topical timolol were not significantly different, 72% (95% CI,
      57%-83%) and 72% (95% CI, 53%-86%), respectively (P=0.98). Significant adverse
      effects were rare. Only 1 case of sleep disturbance was reported across 554
      patients from all studies. CONCLUSIONS: Topically administered beta-blockers are
      an effective treatment for superficial IHs that pose few adverse effects and
      should be considered for primary treatment.

PMID- 25590250
TI  - Outcomes of immediate tissue expander breast reconstruction followed by
      reconstruction of choice in the setting of postmastectomy radiation therapy.

PMID- 25590251
TI  - The use of patient registries in breast surgery: a comparison of the tracking
      operations and outcomes for plastic surgeons and national surgical quality
      improvement program data sets.
AB  - BACKGROUND: The National Surgical Quality Improvement Program (NSQIP) and the
      Tracking Operations and Outcomes for Plastic Surgeons (TOPS) registries gather
      outcomes for plastic surgery procedures. The NSQIP collects hospital data using
      trained nurses, and the TOPS relies on self-reported data. We endeavored to
      compare the TOPS and NSQIP data sets with respect to cohort characteristics and
      outcomes to better understand the strengths and weakness of each registry as
      afforded by their distinct data collection methods. STUDY DESIGN: The 2008 to
      2011 TOPS and NSQIP databases were queried for breast reductions and breast
      reconstructions. Propensity score matching identified similar cohorts from the
      TOPS and NSQIP databases. Shared 30-day surgical and medical complications rates
      were compared across matched cohorts. RESULTS: The TOPS captured a significantly
      greater number of wound dehiscence occurrences (4.77%-5.47% vs 0.69%-1.17%, all
      P<0.001), as well as more reconstructive failures after prosthetic reconstruction
      (2.82% vs 0.26%, P<0.001). Medical complications were greater in NSQIP (P<0.05).
      Other complication rates did not differ across any procedure (all P>0.05).
      CONCLUSIONS: The TOPS and NSQIP capture significantly different patient
      populations, with TOPS' self-reported data allowing for the inclusion of private
      practices. This self-reporting limits TOPS' ability to identify medical
      complications; surgical complications and readmissions, however, were not
      underreported. Many surgical complications are captured by TOPS at a higher rate
      due to its broader definitions, and others are not captured by NSQIP at all. The
      TOPS and NSQIP provide complementary information with different strengths and
      weakness that together can guide evidence-based decision making in plastic
      surgery.

PMID- 25590252
TI  - The impact of conflict of interest in abdominal wall reconstruction with
      acellular dermal matrix.
AB  - INTRODUCTION: Conflict of interest (COI) and disclosure of financial
      relationships have received increased attention recently owing in part to the
      passage of the Physician Payments Sunshine Act, which requires manufacturers of
      drugs, medical devices, and biological to record payments to physicians and
      health care systems. The impact of financial relationships with industry
      sponsorship and COI reporting on surgical outcomes of abdominal wall
      reconstruction with acellular dermal matrices (ADMs) has not been previously
      explored. METHODS: A systematic review of the literature for studies that
      evaluated surgical outcomes in abdominal wall reconstruction using ADM was
      conducted. The level of evidence of these studies was evaluated; and data
      concerning the type of industry, government, or national society sponsorship,
      primary outcome, complications, and statistical results were collected. The
      overall favorability of the study with respect to ADM use was systematically
      assessed. Comparisons between type of sponsorship and significant results were
      analyzed using the Pearson chi2 test. RESULTS: A total of 204 studies were
      identified, of which 124 fulfilled our inclusion criteria. Sixty-four (52%)
      studies had a disclosure statement present. Conflict of interest was reported in
      39 (61%) of these studies. Taken collectively, studies that report no COI are
      more likely to be unfunded (P<0.001). Studies with a reported COI are more likely
      to report a favorable outcome with respect to infection (P<0.01), wound
      complications (P<0.01), and overall morbidity (P<0.07) and mortality (P<0.05).
      CONCLUSIONS: Industry sponsorship and COI are common in abdominal wall
      reconstruction studies with ADM. Studies authored by groups disclosing an
      industry conflict that report clinical outcomes are significantly associated with
      reporting lower postoperative complications, and consequently describing positive
      research findings.

PMID- 25590253
TI  - Outcomes of immediate tissue expander breast reconstruction followed by
      reconstruction of choice in the setting of postmastectomy radiation therapy:
      reply.

PMID- 25590254
TI  - Local anesthetic use in tumescent liposuction: an American Society of Plastic
      Surgeons survey.
AB  - BACKGROUND: Current guidelines favor the use of lidocaine in liposuction wetting
      solutions. The use of bupivacaine as an alternative remains controversial despite
      reports of its use with safe and favorable outcomes suggesting faster
      postoperative recovery time secondary to improved pain control. The goals of this
      study were to determine the prevalence of bupivacaine use, examine liposuction
      practices of bupivacaine users, and elucidate opinions regarding bupivacaine use.
      METHODS: An online survey was distributed to 2500 randomly selected members of
      the American Society of Plastic Surgeons. Data were collected and analyzed with
      special attention toward the practice and opinions of bupivacaine use. RESULTS:
      The response rate of the survey met the average American Society of Plastic
      Surgeons online survey response rate at 12.8% (n=320). Respondents (7.2%; n=22)
      reported using bupivacaine in their wetting solutions (bupivacaine group) and
      provided a dosage range of 62.5 to 150 mg. Respondents (83.5%; n=254) reported
      using either lidocaine or prilocaine (no-bupivacaine group). There were no
      reports of bupivacaine toxicity in 2011. The demographic profile and liposuction
      practices of both groups were comparable. Although 36% of the no-bupivacaine
      group did not know or had no opinion on when it is appropriate to use bupivacaine
      in liposuction wetting solutions, 85% of this group has used bupivacaine for
      other clinical purposes. CONCLUSIONS: A review of 320 plastic surgeons'
      experiences revealed that 7% of respondents are using bupivacaine in their
      tumescent solutions with no reported cases of toxicity. Bupivacaine users
      differed dramatically only in their opinion regarding the safety of bupivacaine
      in tumescent liposuction. The recent studies suggesting better postoperative pain
      control with bupivacaine along with the proportion of respondents reporting
      bupivacaine use call for distinct guidelines on bupivacaine use in liposuction.
      Further studies, including a rigorous clinical trial documenting the safety and
      efficacy of bupivacaine when compared with lidocaine, would be warranted.

PMID- 25590255
TI  - Blepharoptosis correction with buried suture method.
AB  - BACKGROUND: Many surgical techniques have been developed to correct
      blepharoptosis, including the anterior levator resection or advancement,
      tarsoaponeurectomy, and Fasanella-Servat Mullerectomy. However, to minimize
      surgical scarring and reduce the postoperative recovery time, the procedure has
      been developed from a complete incision to a partial incision, which is appealing
      to patients. To aid the procedural development, this study describes a surgical
      technique in which the correction of blepharoptosis and a double eyelid fold
      operation are performed using a buried suture technique during the same
      operation. METHODS: A retrospective review was conducted using the medical
      records and preoperative and postoperative photography of 121 patients who
      underwent simultaneous correction of blepharoptosis and had a double eyelid fold
      created between October 2010 and July 2011. All of the patients had mild (1-2 mm)
      or moderate (3-4 mm) bilateral blepharoptosis and excellent or good levator
      function (>8 mm). RESULTS: The average preoperative marginal reflex distance
      (MRD1) measured 1.174 (0.3) mm. No intraoperative complications occurred. The
      average postoperative MRD1 measured 3.968 (0.2) mm. There was statistical
      significance improvement between preoperative MRD1 and postoperative MRD1
      (P<0.05). No symptomatic dry eye and exposure keratopathy were noted.
      CONCLUSIONS: Blepharoptosis correction using the buried suture technique is an
      effective technique for young patients experiencing mild to moderate
      blepharoptosis who want to have the double eyelid fold operation using the buried
      suture technique.

PMID- 25590256
TI  - Coffee, tea, and chocolate after microsurgery: why not?

PMID- 25590258
TI  - Real-time pathogen monitoring during enrichment: a novel nanotechnology-based
      approach to food safety testing.
AB  - We describe a new approach for the real-time detection and identification of
      pathogens in food and environmental samples undergoing culture. Surface Enhanced
      Raman Scattering (SERS) nanoparticles are combined with a novel homogeneous
      immunoassay to allow sensitive detection of pathogens in complex samples such as
      stomached food without the need for wash steps or extensive sample preparation.
      SERS-labeled immunoassay reagents are present in the cultural enrichment vessel,
      and the signal is monitored real-time through the wall of the vessel while
      culture is ongoing. This continuous monitoring of pathogen load throughout the
      enrichment process enables rapid, hands-free detection of food pathogens.
      Furthermore, the integration of the food pathogen immunoassay directly into the
      enrichment vessel enables fully biocontained food safety testing, thereby
      significantly reducing the risk of contaminating the surrounding environment with
      enriched pathogens. Here, we present experimental results showing the detection
      of E. coli, Salmonella, or Listeria in several matrices (raw ground beef, raw
      ground poultry, chocolate milk, tuna salad, spinach, brie cheese, hot dogs, deli
      turkey, orange juice, cola, and swabs and sponges used to sample a stainless
      steel surface) using the SERS system and demonstrate the accuracy of the approach
      compared to plating results. 

PMID- 25590257
TI  - Surface chemistry of photoluminescent F8BT conjugated polymer nanoparticles
      determines protein corona formation and internalization by phagocytic cells.
AB  - Conjugated polymer nanoparticles are being developed for a variety of diagnostic
      and theranostic applications. The conjugated polymer, F8BT, a polyfluorene
      derivative, was used as a model system to examine the biological behavior of
      conjugated polymer nanoparticle formulations stabilized with ionic (sodium
      dodecyl sulfate; F8BT-SDS; ~207 nm; -31 mV) and nonionic (pegylated 12
      hydroxystearate; F8BT-PEG; ~175 nm; -5 mV) surfactants, and compared with
      polystyrene nanoparticles of a similar size (PS200; ~217 nm; -40 mV). F8BT
      nanoparticles were as hydrophobic as PS200 (hydrophobic interaction
      chromatography index value: 0.96) and showed evidence of protein corona formation
      after incubation with serum-containing medium; however, unlike polystyrene, F8BT
      nanoparticles did not enrich specific proteins onto the nanoparticle surface.
      J774A.1 macrophage cells internalized approximately ~20% and ~60% of the F8BT-SDS
      and PS200 delivered dose (calculated by the ISDD model) in serum-supplemented and
      serum-free conditions, respectively, while cell association of F8BT-PEG was
      minimal (<5% of the delivered dose). F8BT-PEG, however, was more cytotoxic (IC50
      4.5 MUg cm(-2)) than F8BT-SDS or PS200. The study results highlight that F8BT
      surface chemistry influences the composition of the protein corona, while the
      properties of the conjugated polymer nanoparticle surfactant stabilizer used
      determine particle internalization and biocompatibility profile. 

PMID- 25590259
TI  - Survival and growth of Salmonella Typhimurium, Escherichia coli O157:H7 and
      Staphylococcus aureus in eggplant dip during storage.
AB  - Eggplant dip is an internationally popular appetizer, prepared in some instances
      under uncertain hygienic conditions with inconsistent refrigeration. This study
      examined the effects of citric acid on the survival of pathogenic microorganisms
      (Salmonella Typhimurium, Escherichia coli O157:H7 and Staphylococcus aureus) and
      naturally present organisms (lactic acid bacteria, LAB, aerobic bacteria, APC and
      yeast and mold, YM) in eggplant dip during storage. Eggplant dip with 0, 0.2,
      0.4, 0.6 or 0.8% citric acid was inoculated with S. Typhimurium, E. coli O157:H7
      or S. aureus and stored at 4, 10 and 21  degrees C for <=15 d. Throughout the
      study, the survival of the inoculated microorganisms was monitored, and LAB, APC,
      YM numbers and pH were determined. There was no significant (p>0.05) effect of
      citric acid on inoculated S. Typhimurium and E. coli O157:H7. Salmonella and E.
      coli O157:H7 survived >7d with little reduction in viability. Reduction of S.
      aureus viability increased with citric acid concentration and reached>3.0 log10
      CFU/g by 15 d at 4  degrees C. Citric acid had no effect (p>0.05) on the
      background YM during storage at 4, 10 and 21  degrees C or LAB stored at 4 and 10
      degrees C, while at 21  degrees C, 0.6 and 0.8% citric acid significantly
      reduced LAB. Citric acid had no effect (p>0.05) on the APC in samples stored at 4
      degrees C but it had significant effects on samples stored at 10 and 21  degrees
      C. Work reported showed that the use of citric acid at 0.4-0.8% can inhibit the
      growth of S. aureus in eggplant dip, but adequate refrigeration is essential to
      minimize risk from this and other pathogens in this product.

PMID- 25590260
TI  - Norovirus cross-contamination during preparation of fresh produce.
AB  - Infection with human norovirus (HuNoV) is considered a common cause of foodborne
      illness worldwide. Foodborne HuNoV outbreaks may result from consumption of food
      contaminated by an infected food handler in the foodservice environment, in which
      bare-hand contact, lack of hand washing, and inadequate cleaning and disinfection
      are common contributing factors. The goal of this study was to examine cross
      contamination of a HuNoV surrogate, murine norovirus (MNV-1), during common
      procedures used in preparing fresh produce in a food service setting, including
      turning water spigots, handling and chopping Romaine lettuce, and washing hands.
      MNV-1 transfer % was log-transformed to achieve a normal distribution of the data
      and enable appropriate statistical analyses to be performed. MNV-1 transfer
      coefficients varied by surface type, and a greater affinity for human hands and
      chopped lettuce was observed. For example, greater transfer was observed from a
      contaminated stainless steel spigot to a clean hand (24% or 1.4-log transfer %)
      compared to transfer from hand to spigot (0.6% or -0.2-log transfer %). During
      the chopping of Romaine lettuce, MNV-1 was transferred from either a contaminated
      cutting board (25% or 1.4-log transfer %) or knife (~100% or 2.0-log transfer %)
      to lettuce at a significantly greater rate (p>0.05) than from contaminated
      lettuce to the board (2.1% or 0.3-log transfer %) and knife (1.2% or 0.06-log
      transfer %). No significant difference (p>0.05) in MNV-1 transfer coefficients
      was observed between bare hands and Romaine lettuce during handling. For
      handwashing trials, only one hand was inoculated with MNV-1 prior to washing. The
      handwashing methods included rubbing hands under tap water for at least 5s
      (average 2.8-log reduction) or washing hands for at least 20s with liquid soap
      (average 2.9-log reduction) or foaming soap (average 3.0-log reduction), but no
      statistical difference between these reductions was achieved (p>0.05). Despite
      the reductions of MNV-1 observed, residual virions were detected on both hands
      after washing in every replicate trial. This observation reveals that virions are
      transferred from one hand to the other during washing with and without soap. Each
      transfer scenario was repeated at least 9 times, and the data gathered indicate
      that MNV-1 transfers readily between common surfaces during food preparation.
      These data are important for the development of quantitative risk analyses, and
      will assist in the development of appropriate intervention strategies for enteric
      viruses in food preparation. 

PMID- 25590261
TI  - Electron beam inactivation of Tulane virus on fresh produce, and mechanism of
      inactivation of human norovirus surrogates by electron beam irradiation.
AB  - Ionizing radiation, whether by electron beams or gamma rays, is a non-thermal
      processing technique used to improve the microbial safety and shelf-life of many
      different food products. This technology is highly effective against bacterial
      pathogens, but data on its effect against foodborne viruses is limited. A
      mechanism of viral inactivation has been proposed with gamma irradiation, but no
      published study discloses a mechanism for electron beam (e-beam). This study had
      three distinct goals: 1) evaluate the sensitivity of a human norovirus surrogate,
      Tulane virus (TV), to e-beam irradiation in foods, 2) compare the difference in
      sensitivity of TV and murine norovirus (MNV-1) to e-beam irradiation, and 3)
      determine the mechanism of inactivation of these two viruses by e-beam
      irradiation. TV was reduced from 7 log10 units to undetectable levels at target
      doses of 16 kGy or higher in two food matrices (strawberries and lettuce). MNV-1
      was more resistant to e-beam treatment than TV. At target doses of 4 kGy, e-beam
      provided a 1.6 and 1.2 log reduction of MNV-1 in phosphate buffered saline (PBS)
      and Dulbecco's Modified Eagle Medium (DMEM), compared to a 1.5 and 1.8 log
      reduction of TV in PBS and Opti-MEM, respectively. Transmission electron
      microscopy revealed that increased e-beam doses negatively affected the structure
      of both viruses. Analysis of viral proteins by SDS-PAGE found that irradiation
      also degraded viral proteins. Using RT-PCR, irradiation was shown to degrade
      viral genomic RNA. This suggests that the mechanism of inactivation of e-beam was
      likely the same as gamma irradiation as the damage to viral constituents led to
      inactivation.

PMID- 25590262
TI  - CUET-ting edge research.

PMID- 25590263
TI  - Selective growth of ZnO nanorods on hydrophobic Si nanorod arrays.
AB  - In this paper we describe the selective growth of ZnO nanorods (NRs) on top of
      hydrophobic Si NR arrays. The periodic Si NR arrays, prepared through electroless
      chemical etching and HF treatment, functioned as hydrophobic substrates. Droplets
      containing ZnO seeds could be positioned on the Si NR arrays, causing the ZnO
      seeds to deposit selectively upon them, with n-ZnO NR/p-Si NR array
      heterojunctions ultimately forming after hydrothermal growth of ZnO NRs. Because
      of compensation for the difference in refractive index between air and the Si
      substrate, the n-ZnO NR/p-Si NR arrays exhibited excellent absorption ability in
      the visible range. Devices based on these n-ZnO NR/p-Si NR array heterojunctions
      displayed not only rectifying behavior but also photovoltaic effects when
      illuminated with UV light. The low temperature and low cost of this fabrication
      process suggest that the selective growth of n-ZnO NRs on p-Si NR arrays might
      allow such structures to have diverse applications in optoelectronics. 

PMID- 25590264
TI  - Simultaneous recovery of organic and inorganic content of paper deinking residue
      through low-temperature microwave-assisted pyrolysis.
AB  - Significant amounts of paper deinking residue (DIR) has been and is still being
      generated from paper deinking processes, representing both an economic and
      environmental burden for recycled paper mills. Our research on low-temperature
      (<200  degrees C) microwave-assisted (MW-assisted) pyrolysis of DIR allows for
      simultaneously efficient fast separation and recovery of the organic and
      inorganic content of DIR at relatively low temperature and within 15 min. Our
      study is the first highly detailed account of the use low-temperature MW-assisted
      pyrolysis to effect this change. The obtained liquid and solid products were
      characterized by a variety of analytical techniques (e.g., attenuated total
      reflection infrared, gas chromatography-mass spectrometry, liquid-state nuclear
      magnetic resonance (NMR), X-ray diffraction, solid-state cross-polarization/magic
      angle spinning (13)C NMR, and Bloch-decay (13)C NMR). The results reveal that the
      process efficiently separates the inorganic minerals as microwave residue (mainly
      calcite and kaolinite) from organic matter, and hence the microwave residue could
      be reused to produce new paper/cardboard products. The organic fraction bio-oil
      generated is energy-densified and rich in carbohydrates and is a potential source
      for valuable aromatic compounds.

PMID- 25590265
TI  - The Trajectory of Long-Term Psychosocial Development 16 Years following Childhood
      Traumatic Brain Injury.
AB  - Childhood traumatic brain injury (CTBI) is one of the most common causes of
      impairment in children and adolescents, with psychosocial difficulties found to
      be the most persisting. Given that the transition into adolescence and adulthood
      can be a stressful period, it is likely that young people who have sustained a
      CTBI will be more vulnerable to developing psychosocial problems. To date, most
      research has focused on psychosocial development up to five years following a
      CTBI and it is unclear how survivors develop in the long-term as young adults.
      The aim of this research was to track the long-term psychosocial outcomes of
      children with CTBI and compare them with healthy controls over a period of 16
      years. Seventy-five participants with a CTBI and 29 control participants were
      followed up at five time-points over a period of 16 years. To measure
      psychosocial functioning (social skills, internalizing, and externalizing
      symptoms), questionnaires were completed by the primary caregiver acutely (pre
      injury baseline), then six months, five years, 10 years, and 16 years post
      injury. No significant group differences were found regarding the developmental
      trajectory of social skills, or internalizing and externalizing symptoms between
      the CTBI and control groups. The severe CTBI group demonstrated a trend of lower
      social skills, while the mild CTBI group showed a trend of higher internalizing
      and externalizing skills at six months, five years, and ten years post-CTBI
      event, compared with other groups. The mild CTBI group scored in the borderline
      range for externalizing symptoms six months post-CTBI; however, all other mean
      scores were within the normal range. Over a period of 16 years, young adults with
      CTBI showed similar developmental trajectories regarding psychosocial outcomes,
      compared with healthy controls. This study confirmed previous literature that
      CTBI is associated with increased levels of psychosocial problems. 

PMID- 25590266
TI  - CD11c+CD123Low dendritic cell subset and the triad TNF-alpha/IL-17A/IFN-gamma
      integrate mucosal and peripheral cellular responses in HIV patients with high
      grade anal intraepithelial neoplasia: a systems biology approach.
AB  - BACKGROUND: The incidence of anal cancer has increased over the past 25 years,
      and HIV/HPV coinfection is the most important risk factor for anal squamous cell
      carcinoma. In this study, we demonstrated that the evaluation of systemic and
      compartmentalized anal mucosa immune response is relevant to differentiating
      HIV(+) patients at risk of anal intraepithelial neoplasia (AIN). METHODS: A
      systems biology approach was used to integrate different immunological parameters
      from anal mucosal tissue and peripheral blood assessed by phenotypic and
      intracytoplasmic analysis of lymphocytes and dendritic cell subsets. RESULTS: Our
      data demonstrated that anal mucosal mononuclear cells from AIN(+)HIV(+) patients
      showed a robust capacity in producing proinflammatory/regulatory cytokines,
      mainly mTNF-alpha > IL-4 > IL-10 > IL-6 = IL-17A. Mucosal TNF-alpha/IFN-gamma/IL
      17A are selective high-grade squamous intraepithelial lesion (HSIL)-related
      biomarkers. Higher levels of circulating CD11cCD123cells and CD1a cells along
      with elevated levels of IFN-gammaCD4 T cells are major features associated with
      HSIL in AIN(+)HIV(+) patients. Regardless of the presence of AIN, HIV(+) patients
      presented a complex biomarker network, rich in negative connections. Among those
      patients, however, HSIL+ patients displayed stronger positive links between
      peripheral blood and anal mucosa environments, exemplified by the subnet of IL
      17A/TNF-alpha/CD4IFN-gamma/CD11cCD123 cells. CONCLUSIONS: The significant
      association between HSIL and the levels of TNF-alpha/IL-17A/IFN-gamma along with
      the different subsets of DCs present in the anal mucosa milieu should be studied
      in more detail as a way to identify and categorize HIV(+) patients vis a vis the
      high risk of anal cancer outcome.

PMID- 25590267
TI  - HIV through the looking glass: insights derived from Hepatitis B.
AB  - BACKGROUND: Although higher levels of hepatitis B virus (HBV) replication in HIV
      HBV co-infection may relate to liver disease progression, this has not been
      completely elucidated. We used expression of hepatitis B core antigen (HBcAg) in
      liver biopsies from HIV-HBV co-infected and HBV mono-infected patients as a
      marker for HBV replication, and related these findings to clinical and
      histological parameters. METHODS: Data from 244 HBV patients were compared with
      34 HIV-HBV patients. Liver biopsies were scored for inflammation, fibrosis,
      HBcAg, and hepatitis B surface antigen. Univariate and multivariate analyses were
      performed. RESULTS: HBcAg, but not hepatitis B surface antigen, staining was
      stronger in HIV co-infected than in HBV mono-infected. Co-infected and HBV mono
      infected had similar alanine aminotransferase, inflammatory and fibrosis scores,
      and hepatitis B e antigen status. HBcAg staining correlated with HIV after
      correcting for HBV DNA and hepatitis B e antigen. CD4 counts and HIV RNA level
      did not correlate with intensity of HBcAg staining. HBV DNA levels were higher in
      HIV co-infected and correlated with HBcAg staining. CONCLUSIONS: By looking at
      HBcAg as a reflection of HBV replication in HIV-HBV co-infected with controlled
      HIV, our findings suggest that these patients may have subtle immune function
      defects, which could lead to adverse liver disease outcomes.

PMID- 25590268
TI  - Diagnostic utility of quantitative plasma cytomegalovirus DNA PCR for
      cytomegalovirus end-organ diseases in patients with HIV-1 infection.
AB  - OBJECTIVE: To investigate the diagnostic value of quantitative plasma
      cytomegalovirus (CMV)-DNA polymerase chain reaction (PCR) for CMV end-organ
      diseases (CMV-EOD) in patients with HIV-1 infection. DESIGN: Single-center cross
      sectional study. METHODS: The study subjects were HIV-1-infected patients with
      CD4 <=200 per microliter, who had undergone ophthalmologic examination with
      plasma CMV-DNA PCR measured within 7 days. CMV retinitis and other CMV-EOD were
      diagnosed according to the ACTG criteria. PCR value was converted into the WHO
      international standard. RESULTS: CMV retinitis and all CMV-EOD were diagnosed in
      23 (5%) and 37 (8%) of the 461 study patients, respectively. CMV-DNA was
      undetectable (<185 IU/mL) in 2 patients with CMV retinitis and 1 with
      encephalitis. The area under the receiver operating characteristic curve of CMV
      DNA for CMV retinitis and all CMV-EOD were 0.80 [95% confidence interval (CI):
      0.71 to 0.89] and 0.82 (0.75 to 0.89), respectively. The sensitivity,
      specificity, positive predictive value, and negative predictive value for each
      cutoff value of CMV-DNA were as follows: for CMV retinitis, >=10,086 IU/mL:
      26.1%, 94.1%, 18.8%, 96%; >=2946 IU/mL; 56.5%, 86.8%, 18.3%, 97.4%; >=959 IU/mL;
      60.9%, 78.1%, 12.7%, 97.4%; detectable CMV-DNA (>=185 IU/mL): 91.3%, 48.2%, 8.5%,
      99.1%; for all CMV-EOD: >=10,086 IU/mL: 32.4%, 95.3%, 37.5%, 94.2%; >=2946 IU/mL;
      54.1%, 88%, 28.2%, 95.6%; >=959 IU/mL; 62.2%, 79.5%, 20.9%, 96%; detectable CMV
      DNA; 91.9%, 49.5%, 13.7%, 98.6%. CONCLUSIONS: Plasma CMV-DNA PCR has a high
      diagnostic value for both CMV retinitis and all CMV-EOD in patients with advanced
      HIV-1 infection. A cutoff value of CMV-DNA >=10,086 IU/mL and >=2946 IU/mL yields
      high specificity, whereas undetectable CMV-DNA load (<185 IU/mL) likely rules out
      CMV-EOD.

PMID- 25590269
TI  - Stimulant use patterns and HIV transmission risk among HIV-serodiscordant male
      couples.
AB  - BACKGROUND: Substance use is strongly linked to HIV risk, and members of couples
      can have a powerful influence on each other's health behaviors. We examined
      whether couple-level patterns of stimulant use were differentially associated
      with engaging in condomless anal intercourse with primary partners and outside
      partners. METHODS: Members of HIV serodiscordant male couples (N = 117 couples,
      232 men) completed surveys, and HIV-positive men had blood drawn for viral load.
      RESULTS: Results revealed that stimulant use by only one partner in the couple
      was associated with a decrease in the odds of engaging in condomless anal sex
      with one's primary partner (AOR = 0.09, 95% CI: 0.01, 0.89). When both partners
      reported stimulant use, the HIV-negative partner had an increase in the odds of
      condomless sex with outside partners (AOR = 6.68, 95% CI: 1.09, 8.01).
      CONCLUSIONS: Understanding the role of couples' stimulant use patterns in HIV
      transmission risk is an important area for future research and intervention.

PMID- 25590270
TI  - Rates and correlates of antiretroviral therapy use and virologic suppression
      among perinatally and behaviorally HIV-infected youth linked to care in the
      United States.
AB  - OBJECTIVE: To measure rates of antiretroviral therapy (ART) use and virologic
      suppression among perinatally HIV-infected youth (PIY) and behaviorally HIV
      infected youth (BIY) linked to care in the United States and examine the effects
      of demographic, biomedical, and psychosocial factors on those rates. METHODS:
      Between 2009 and 2012, 649 PIY and 1547 BIY in 20 Adolescent Medicine Trials
      Network for HIV/AIDS Interventions sites completed cross-sectional surveys
      through audio computer-assisted self-interviews. Viral load data were collected
      from chart abstraction or blood draw. RESULTS: Overall 82.4% of PIY and 49.1% of
      BIY reported current ART use. Only 37.0% of PIY and 27.1% of BIY were
      virologically suppressed. Virologic suppression rates did not vary as a function
      of time since HIV diagnosis in either group. Consistent HIV care and no current
      substance abuse were significant correlates of ART use among PIY. These variables
      and non-African American race were some factors associated with virologic
      suppression for PIY [odds ratios (ORs) P < 0.05]. Among BIY, older age,
      heterosexuals, employment, and education were significantly related to ART use
      (ORs: P < 0.05); suppression was related to ART use >=6 months, >=90% ART
      adherence, and consistent HIV care (ORs: P < 0.05). Nearly 75% (n = 498) of
      nonsuppressed youth reported unprotected sex in the past 3 months. CONCLUSIONS:
      There are continued challenges with successfully treating youth even once
      diagnosed and linked to HIV care. Strategies targeting barriers to ART access,
      use, and virologic suppression are needed to optimize the impact of the
      "Treatment as Prevention" paradigm among PIY and BIY.

PMID- 25590271
TI  - Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS
      in Asia: results from the TREAT Asia HIV observational database.
AB  - BACKGROUND: Roughly 4% of the 1.25 million patients on antiretroviral therapy
      (ART) in Asia are using second-line therapy. To maximize patient benefit and
      regional resources, it is important to optimize the timing of second-line ART
      initiation and use the most effective compounds available. METHODS: HIV-positive
      patients enrolled in the TREAT Asia HIV Observational Database who had used
      second-line ART for >=6 months were included. ART use and rates and predictors of
      second-line treatment failure were evaluated. RESULTS: There were 302 eligible
      patients. Most were male (76.5%) and exposed to HIV via heterosexual contact
      (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell
      count was 146 cells per cubic millimeter, and median HIV viral load was 16,224
      copies per milliliter. Patients started second-line ART before 2007 (n = 105),
      2007-2010 (n = 147) and after 2010 (n = 50). Ritonavir-boosted lopinavir and
      atazanavir accounted for the majority of protease inhibitor use after 2006.
      Median follow-up time on second-line therapy was 2.3 years. The rates of
      treatment failure and mortality per 100 patient/years were 8.8 (95% confidence
      interval: 7.1 to 10.9) and 1.1 (95% confidence interval: 0.6 to 1.9),
      respectively. Older age, high baseline viral load, and use of a protease
      inhibitor other than lopinavir or atazanavir were associated with a significantly
      shorter time to second-line failure. CONCLUSIONS: Increased access to viral load
      monitoring to facilitate early detection of first-line ART failure and subsequent
      treatment switch is important for maximizing the durability of second-line
      therapy in Asia. Although second-line ART is highly effective in the region, the
      reported rate of failure emphasizes the need for third-line ART in a small
      portion of patients.

PMID- 25590272
TI  - Pregnancy and contraceptive use among women participating in the FEM-PrEP trial.
AB  - BACKGROUND: Pregnancy among study participants remains a challenge for trials of
      new HIV prevention agents despite promotion and provision of contraception. We
      evaluated contraceptive use, pregnancy incidence, and study drug adherence by
      contraceptive method among women enrolled in the FEM-PrEP trial of once-daily
      oral tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) for HIV
      prevention. METHODS: We required women to be using effective non-barrier
      contraception at enrollment. At each monthly follow-up visit, women were
      counseled on contraceptive use and tested for pregnancy. TDF-FTC adherence was
      determined by measuring plasma drug concentrations at 4-week intervals. We used
      Cox proportional hazards models to assess factors associated with incident
      pregnancy and multivariate logistic regression to examine the relationship
      between contraceptive method used at enrollment and TDF-FTC adherence. RESULTS:
      More than half of women were not using effective contraception before enrollment.
      Ninety-eight percent of these women adopted either injectable (55%) or oral (43%)
      contraceptives. The overall pregnancy rate was 9.6 per 100 woman-years. Among
      injectable users and new users of combined oral contraceptives (COCs), the rates
      were 1.6 and 35.1, respectively. New users of injectables had significantly
      greater odds of adhering to TDF-FTC than new COC users [odds ratio (95%
      confidence interval): 4.4 (1.7 to 11.6), P = 0.002], existing COC users [3.1 (1.3
      to 7.3), P = 0.01], and existing injectable users [2.4 (1.1 to 5.6), P = 0.04].
      CONCLUSIONS: Women using COCs during FEM-PrEP, particularly new adopters, were
      more likely to become pregnant and less likely to adhere to study product than
      injectable users. HIV prevention trials should consider requiring long-acting
      methods, including injectables, for study participation.

PMID- 25590273
TI  - Viremia copy-years as a predictive marker of all-cause mortality in HIV-1
      infected patients initiating a protease inhibitor-containing antiretroviral
      treatment.
AB  - BACKGROUND: Viremia copy-years (VCY) has been reported as a short-term predictor
      of mortality. We evaluated the association of this parameter with 10-year outcome
      within the APROCO-COPILOTE cohort. METHODS: Prospective data from 1281 HIV-1
      infected patients who started a first protease inhibitor-containing regimen in
      1997-1999 were analyzed. Patients with baseline plasma viral load (pVL) > 500
      copies per milliliter and at least 2 pVL measures from the eighth month of follow
      up were selected. VCY was calculated individually over the follow-up as the area
      under the pVL curve. Multivariate Cox models analyzed the relation between all
      cause mortality and the following variables: age, sex, geographical origin,
      transmission group, HIV infection duration, ART-naive, pVL at baseline, time
      dependent CD4 count, and VCY. RESULTS: Nine hundred seventy-nine patients were
      followed up for a median of 10 years (interquartile range: 5-11.5). At baseline,
      median (interquartile range) values for duration of HIV infection, pVL, and CD4
      cell count were 43 (4-95) months, 4.6 (3.9-5.2) log10 copies per milliliter, and
      278 (125-416) cells per cubic millimeter, respectively. At censoring date, 77
      patients (8%) had died. VCY >1.4 log10 copies * yrs/mL was an independent
      predictor of death (hazard ratio: 2.0; 95% confidence interval: 1.2 to 3.5),
      which was no longer the case after adjustment for the latest pVL value [risk
      ratio (RR): 1.2 for 1 additional log10 copies per milliliter; 95% confidence
      interval: 1.1 to 1.4]. CONCLUSIONS: VCY was associated with mortality in HIV
      infected patients under combined antiretroviral therapy but did not overweigh the
      predictive value of the latest pVL. VCY might be more useful as a marker of
      persistent viral replication than for routine clinical care.

PMID- 25590274
TI  - Dynamics of HIV DNA and residual viremia in patients treated with a raltegravir
      containing regimen.

PMID- 25590275
TI  - A run-in period is needed in randomized controlled trials of directly observed
      antiretroviral therapy for HIV infection.

PMID- 25590276
TI  - Nephroprotective role of resveratrol and ursolic Acid in aristolochic Acid
      intoxicated zebrafish.
AB  - The nephrotoxicity of aristolochic acid (AA) is well known, but information
      regarding the attenuation of AA-induced toxicity is limited. The aim of the
      present study was to study the nephroprotective effects of resveratrol (Resv) and
      ursolic acid (UA) in a zebrafish model. We used two transgenic lines,
      Tg(wt1b:EGFP) and Tg(gata1:DsRed), to evaluate the nephroprotective effects of
      Resv and UA by recording subtle changes in the kidney and red blood cell
      circulation. Our results demonstrated that both Resv and UA treatment can
      attenuate AA-induced kidney malformations and improve blood circulation.
      Glomerular filtration rate assays revealed that both Resv and UA treatment can
      restore renal function (100% for Mock; 56.1% +/- 17.3% for AA-treated; 80.2% +/-
      11.3% for Resv+AA; and 83.1% +/- 8.1% for UA+AA, n = 15). Furthermore, real-time
      RT-PCR experiments showed that pre-treatment with either Resv or UA suppresses
      expression of pro-inflammatory genes. In conclusion, our findings reveal that AA
      induced nephrotoxicities can be attenuated by pre-treatment with either Resv or
      UA. Therefore, we believe that zebrafish represent an efficient model for
      screening AA-protective natural compounds. 

PMID- 25590277
TI  - The cytolytic activity of vaginolysin strictly depends on cholesterol and is
      potentiated by human CD59.
AB  - Gardnerella vaginalis produces cytolysin vaginolysin (VLY), which has been
      suggested to be a contributor to bacterial vaginosis pathogenesis. VLY along with
      intermedilysin (ILY) from Streptococcus intermedius have been attributed to a
      group of cholesterol-dependent cytolysins (CDCs) whose pore-forming activity
      depends on human CD59 (hCD59). Here, we show that different types of cells
      lacking hCD59 are susceptible to VLY-mediated lysis, albeit to different extents.
      We analyze the effects of both hCD59 and cholesterol on VLY cytolytic activity.
      We show that VLY binds to cholesterol-rich membranes of non-human cells, while
      VLY with an impaired cholesterol recognition site retains binding to the hCD59
      containing cells. We further demonstrate that cholesterol binding by VLY is
      sufficient to trigger the formation of oligomeric complexes on cholesterol rich
      liposomes lacking hCD59. Thus, VLY may induce cell lysis following two
      alternative pathways. One requires only cholesterol and does not depend on hCD59.
      The second pathway involves hCD59 contribution similarly to ILY. Apparently,
      under physiological conditions VLY acts in the most effective way by accepting
      the assistance of hCD59. 

PMID- 25590279
TI  - Minimally invasive management of urological fistulas.
AB  - PURPOSE OF REVIEW: Urological fistulas are an underestimated problem worldwide
      and have devastating consequences for patients. Many urological fistulas result
      from surgical complications and/or inadequate perinatal obstetric healthcare.
      Surgical correction is the standard treatment. This article reviews minimally
      invasive surgical approaches to manage urological fistulas with a particular
      emphasis on the robotic techniques of fistula correction. RECENT FINDINGS: In
      recent years, many surgeons have explored a minimally invasive approach for the
      management of urological fistulas. Several studies have demonstrated the
      feasibility of laparoscopic surgery and the reproducibility of reconstructive
      surgery techniques. Introduction of the robotic platform has provided significant
      advantages given the improved dexterity and exceptional vision that it confers.
      SUMMARY: Fistulas are a concern worldwide. Laparoscopic surgery correction has
      been developed through the efforts of several authors, and difficulties such as
      the increased learning curve have been overcome with innovations, including the
      robotic platform. Although minimally invasive surgery offers numerous advantages,
      the most successful approach remains the one with the surgeon is most familiar.

PMID- 25590278
TI  - Increased circulating levels of vitamin D binding protein in MS patients.
AB  - Vitamin D (vitD) low status is currently considered a main environmental factor
      in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites
      are highly hydrophobic and circulate mostly bound to the vitamin D binding
      protein (DBP) and with lower affinity to albumin, while less than 1% are in a
      free form. The aim of this study was to investigate whether the circulating
      levels of either of the two vitD plasma carriers and/or their relationship are
      altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24
      healthy controls. MS patients were found to have higher DBP levels than healthy
      subjects. Concomitant interferon beta therapy did not influence DBP
      concentration, and the difference with the control group was significant in both
      females and males. No significant correlation between DBP and albumin levels was
      observed either in healthy controls or in patients. These observations suggest
      the involvement of DBP in the patho-physiology of MS. 

PMID- 25590280
TI  - Anatomic partial nephrectomy: technique evolution.
AB  - PURPOSE OF REVIEW: Partial nephrectomy provides equivalent long-term oncologic
      and superior functional outcomes as radical nephrectomy for T1a renal masses.
      Herein, we review the various vascular clamping techniques employed during
      minimally invasive partial nephrectomy, describe the evolution of our partial
      nephrectomy technique and provide an update on contemporary thinking about the
      impact of ischemia on renal function. RECENT FINDINGS: Recently, partial
      nephrectomy surgical technique has shifted away from main artery clamping and
      towards minimizing/eliminating global renal ischemia during partial nephrectomy.
      Supported by high-fidelity three-dimensional imaging, novel anatomic-based
      partial nephrectomy techniques have recently been developed, wherein partial
      nephrectomy can now be performed with segmental, minimal or zero global ischemia
      to the renal remnant. Sequential innovations have included early unclamping,
      segmental clamping, super-selective clamping and now culminating in anatomic zero
      ischemia surgery. By eliminating 'under-the-gun' time pressure of ischemia for
      the surgeon, these techniques allow an unhurried, tightly contoured tumour
      excision with point-specific sutured haemostasis. Recent data indicate that zero
      ischemia partial nephrectomy may provide better functional outcomes by
      minimizing/eliminating global ischemia and preserving greater vascularized kidney
      volume. SUMMARY: Contemporary partial nephrectomy includes a spectrum of surgical
      techniques ranging from conventional-clamped to novel zero-ischemia approaches.
      Technique selection should be tailored to each individual case on the basis of
      tumour characteristics, surgical feasibility, surgeon experience, patient
      demographics and baseline renal function.

PMID- 25590281
TI  - Enhanced functionality and stabilization of a cold active laccase using
      nanotechnology based activation-immobilization.
AB  - A simple nanotechnology based immobilization technique for imparting
      psychrostability and enhanced activity to a psychrophilic laccase has been
      described here. Laccase from a psychrophile was supplemented with Copper oxide
      nanoparticles (NP) corresponding to copper (NP-laccase), the cationic activator
      of this enzyme and entrapped in single walled nanotube (SWNT). The activity and
      stability of laccase was enhanced both at temperatures as low as 4 degrees C and
      as high as 80 degrees C in presence of NP and SWNT. The enzyme could be released
      and re-trapped (in SWNT) multiple times while retaining significant activity.
      Laccase, immobilized in SWNT, retained its activity after repeated freezing and
      thawing. This unique capability of SWNT to activate and stabilize cold active
      enzymes at temperatures much lower or higher than their optimal range may be
      utilized for processes that require bio-conversion at low temperatures while
      allowing for shifts to higher temperature if so required. 

PMID- 25590282
TI  - Focus formation: a cell-based assay to determine the oncogenic potential of a
      gene.
AB  - Malignant transformation of cells is typically associated with increased
      proliferation, loss of contact inhibition, acquisition of anchorage-independent
      growth potential, and the ability to form tumors in experimental animals(1). In
      NIH 3T3 cells, the Ras signal transduction pathway is known to trigger many of
      these events, what is known as Ras transformation. The introduction of an
      overexpressed gene in NIH 3T3 cells may promote morphological transformation and
      loss of contact inhibition, which can help determine the oncogenic potential of
      that gene of interest. An assay that provides a straightforward method to assess
      one aspect of the transforming potential of an oncogene is the Focus Formation
      Assay (FFA)(2). When NIH 3T3 cells divide normally in culture, they do so until
      they reach a confluent monolayer. However, in the presence of an overexpressed
      oncogene, these cells can begin to grow in dense, multilayered foci(1) that can
      be visualized and quantified by crystal violet or Hema 3 staining. In this
      article we describe the FFA protocol with retroviral transduction of the gene of
      interest into NIH 3T3 cells, and how to quantify the number of foci through
      staining. Retroviral transduction offers a more efficient method of gene delivery
      than transfection, and the use of an ecotropic murine retrovirus provides a
      biosafety control when working with potential human oncogenes. 

PMID- 25590283
TI  - Flexible ferroelectric polymer devices based on inkjet-printed electrodes from
      nanosilver ink.
AB  - High-quality silver (Ag) patterns were inkjet-printed with nanosilver ink on a
      flexible polyethylene terephthalate (PET) substrate. All-solution-processed
      flexible ferroelectric polymer devices that use inkjet-printed Ag to create their
      bottom and top electrodes were demonstrated. The active layer, a poly (vinylidene
      fluoride-trifluoroethylene) (PVDF-TrFE) thin film, was spin-coated from solution.
      The devices have a remanent polarization of 8.03 MUC cm(-2) and a coercive field
      of 68.5 MV m(-1), which is comparable to the device with evaporated-Ti electrodes
      on a silicon substrate. Based on the results presented in this paper, mass
      production of flexible ferroelectric devices is predictable. 

PMID- 25590285
TI  - Long-ranged and soft interactions between charged colloidal particles induced by
      multivalent coions.
AB  - Forces between charged particles in aqueous solutions containing multivalent
      coions and monovalent counterions are studied by the colloidal probe technique.
      Here, the multivalent ions have the same charge as the particles, which must be
      contrasted to the frequently studied case where multivalent ions have the
      opposite sign as the substrate. In the present case, the forces remain repulsive
      and are dominated by the interactions of the double layers. The valence of the
      multivalent coion is found to have a profound influence on the shape of the force
      curve. While for monovalent coions the force profile is exponential down to
      separations of a few nanometers, the interaction is much softer and longer-ranged
      in the presence of multivalent coions. The force profiles in the presence of
      multivalent coions and in the mixtures of monovalent and multivalent coions can
      be accurately described by Poisson-Boltzmann theory. These results are accurate
      for different surfaces and even in the case of highly charged particles. This
      behavior can be explained by the fact that the force profile follows the near
      field limit to much larger distances for multivalent coions than for monovalent
      ones. This limit corresponds to the conditions with no salt, where the coions are
      expelled between the two surfaces. 

PMID- 25590284
TI  - A novel vertebral stabilization method for producing contusive spinal cord
      injury.
AB  - Clinically-relevant animal cervical spinal cord injury (SCI) models are essential
      for developing and testing potential therapies; however, producing reliable
      cervical SCI is difficult due to lack of satisfactory methods of vertebral
      stabilization. The conventional method to stabilize the spine is to suspend the
      rostral and caudal cervical spine via clamps attached to cervical spinous
      processes.  However, this method of stabilization fails to prevent tissue
      yielding during the contusion as the cervical spinal processes are too short to
      be effectively secured by the clamps (Figure 1).  Here we introduce a new method
      to completely stabilize the cervical vertebra at the same level of the impact
      injury.  This method effectively minimizes movement of the spinal column at the
      site of impact, which greatly improves the production of consistent SCIs.  We
      provide visual description of the equipment (Figure 2-4), methods, and a step-by
      step protocol for the stabilization of the cervical 5 vertebra (C5) of adult
      rats, to perform laminectomy (Figure 5) and produce a contusive SCI thereafter. 
      Although we only demonstrate a cervical hemi-contusion using the NYU/MASCIS
      impactor device, this vertebral stabilization technique can be applied to other
      regions of the spinal cord, or be adapted to other SCI devices.  Improving spinal
      cord exposure and fixation through vertebral stabilization may be valuable for
      producing consistent and reliable injuries to the spinal cord.  This vertebral
      stabilization method can also be used for stereotactic injections of cells and
      tracers, and for imaging using two-photon microscopy in various neurobiological
      studies. 

PMID- 25590286
TI  - Applicability of an anti-trichophyton monoclonal antibody for the
      immunohistochemical diagnosis of human fungal skin infections (dermatophytosis)
      in tissue sections.

PMID- 25590287
TI  - Metastatic atypical fibroxanthoma: a series of 11 cases including with minimal
      and no subcutaneous involvement.
AB  - Atypical fibroxanthoma (AFX) is a dermal mesenchymal neoplasm arising in sun
      damaged skin, primarily of the head and neck region of older men. Conservative
      excision cures most. However, varying degrees of subcutaneous involvement can
      lead to a more aggressive course and rare metastases. Thus, AFX involving the
      subcutis are termed pleomorphic dermal sarcomas or other monikers by some to
      recognize the more threatening natural history. We reviewed cases of "metastatic
      AFX" from our institution and from the files of a consultative dermatopathology
      practice. Nine of 152 patients with AFX were identified at a single institution
      (2000-2011). Two additional patients were identified from the files of a
      consultative practice. Clinical, radiological, and pathological features were
      reviewed and cases with histologically verified metastases identified. Median age
      was 67 (range, 45-91) years, all male, and involving the head and neck region.
      Two cases had no documented involvement of the subcutis, and 2 cases had only
      superficial subcutis involvement. Median time to metastases was 13 (range, 8-49)
      months. Three patients developed solitary regional lymph node metastases while 8
      had widespread metastases. Five patients developed local recurrence within 8
      months, and all 5 developed widespread metastasis. With median follow-up of 26
      (range, 10-145) months, 6 died of disease (median, 19 months; range, 10-35
      months), 4 were alive and well, and 1 was alive with disease. AFX has very rare
      metastatic potential, even those without or with minimal subcutis involvement,
      and can lead to mortality. Most metastasis and local recurrence occurred within 1
      year of presentation. Solitary regional metastases were associated with better
      outcomes than those with multiple distant metastases. Patients with repeated
      local recurrences portended more aggressive disease including development of
      distant metastases. 

PMID- 25590288
TI  - Primary cutaneous marginal IgG4 lymphoma and Rosai-Dorfman's disease coexisting
      in several lesions of the same patient.
AB  - We report the unique association of primary cutaneous marginal zone B-cell
      lymphoma and Rosai-Dorfman disease (RDD)-type histiocytic infiltrates involving
      the same lesions. The patient was an 82-year-old woman with 3 long-standing, well
      circumscribed firm erythematous to brownish plaques on her left arm, right
      scapular area, and lumbosacral area. Histopathologic examination disclosed a
      dermal and subcutaneous nodular lymphoplasmacytic infiltrate with evidence of
      germinal center colonization and light-chain restriction and sheets of S-100 CD68
      positive histiocytes with ample pale cytoplasm and occasional emperipolesis of
      lymphocytes. The neoplastic plasma cells expressed immunoglobulin (Ig) G4. A
      review of 14 examples of cutaneous RDD showed a substantial number of IgG4
      positive cells in only 3 of them, and a review of 8 primary cutaneous marginal
      zone B-cell lymphomas disclosed only 2 with significant IgG4 expression. The
      coexistence of lymphomas and RDD has been rarely reported in the literature but
      only seldom involving the same lymph node and-to the best of our knowledge-never
      in the skin. 

PMID- 25590289
TI  - Ketoconazole-induced Sweet syndrome: a new association.
AB  - Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis that can be
      associated with malignancy and medications. A 60-year-old man presented with
      erythematous, edematous, and ulcerated plaques in the extensor surface of the
      upper extremities, after a ketoconazole course due to pityrosporum folliculitis.
      Skin biopsy showed a dense dermal neutrophilic infiltrate, associated with marked
      papillary dermal edema. Blood count showed leukocytosis and neutrophilia. Skin
      lesions resolved spontaneously with discoloration after 2 weeks of
      discontinuation of ketoconazole. Although most cases of drug-induced SS are
      associated with granulocyte colony-stimulating factor, other medications need to
      be considered. This is the first reported case of ketoconazole-induced SS despite
      its widespread use.

PMID- 25590291
TI  - Sleep: soothing and restorative.

PMID- 25590290
TI  - Homocysteine-lowering interventions for preventing cardiovascular events.
AB  - BACKGROUND: Cardiovascular disease, which includes coronary artery disease,
      stroke and congestive heart failure, is a leading cause of death worldwide.
      Homocysteine is an amino acid with biological functions in methionine metabolism.
      A postulated risk factor is an elevated circulating total homocysteine level,
      which is associated with cardiovascular events. The impact of homocysteine
      lowering interventions, given to patients in the form of vitamins B6, B9 or B12
      supplements, on cardiovascular events. This is an update of a review previously
      published in 2009 and 2013. OBJECTIVES: To determine whether homocysteine
      lowering interventions, provided in patients with and without pre-existing
      cardiovascular disease are effective in preventing cardiovascular events, as well
      as all-cause mortality and evaluate their safety. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 1), MEDLINE
      (1950 to January week 5 2014), EMBASE (1980 to 2014 week 6) and LILACS (1986 to
      February 2014). We also searched Web of Science (1970 to 7 February 2014). We
      handsearched the reference lists of included papers. We also contacted
      researchers in the field. There was no language restriction in the search.
      SELECTION CRITERIA: We included randomised controlled trials assessing the
      effects of homocysteine-lowering interventions for preventing cardiovascular
      events with a follow-up period of one year or longer. We considered myocardial
      infarction and stroke as the primary outcomes. We excluded studies in patients
      with end-stage renal disease. DATA COLLECTION AND ANALYSIS: We performed study
      selection, 'Risk of bias' assessment and data extraction in duplicate. We
      estimated risk ratios (RR) for dichotomous outcomes. We measured statistical
      heterogeneity using the I(2) statistic. We used a random-effects model. MAIN
      RESULTS: In this second updated Cochrane Review, we identified no new randomised
      controlled trials. Therefore, this new version includes 12 randomised controlled
      trials involving 47,429 participants. In general terms, 75% (9/12) trials had a
      low risk of bias. Homocysteine-lowering interventions compared with placebo did
      not significantly affect non-fatal or fatal myocardial infarction (1743/23,590
      (7.38%) versus 1247/20,190 (6.17%); RR 1.02, 95% confidence interval (CI) 0.95 to
      1.10, I(2) = 0%, high quality evidence), stroke (968/22,348 (4.33%) versus
      974/18,957 (5.13%); RR 0.91, 95% CI 0.82 to 1.0, I(2) = 11%, high quality
      evidence) or death from any cause (2784/22,648 (12.29%) versus 2502/19,250
      (10.64%); RR 1.01, 95% CI 0.96 to 1.07, I(2) = 6%, high quality evidence).
      Homocysteine-lowering interventions compared with placebo did not significantly
      affect serious adverse events (cancer) (1558/18,130 (8.59%) versus 1334/14,739
      (9.05%); RR 1.06, 95% CI 0.98 to 1.13; I(2) = 0%, high quality evidence).
      AUTHORS' CONCLUSIONS: This second update of this Cochrane Review found no
      evidence to suggest that homocysteine-lowering interventions in the form of
      supplements of vitamins B6, B9 or B12 given alone or in combination should be
      used for preventing cardiovascular events. Furthermore, there is no evidence to
      suggest that homocysteine-lowering interventions are associated with an increased
      risk of cancer.

PMID- 25590292
TI  - The effects of simultaneous exercise and psychotherapy on depressive symptoms in
      inpatient, psychiatric older adults.
AB  - CONTEXT: Depression is the leading cause of early death, affecting 15% of
      Americans older than 65 y and costing $43 billion each year. The current mental
      health service system for seniors, particularly for the population hospitalized
      in acute inpatient psychiatric units, is fragmented because of poor funding and a
      shift to a transitory health care paradigm, leading to inadequate treatment
      modalities, questionable quality of care, and lack of research demonstrating the
      superiority of a particular treatment. These issues are likely to lead to a
      public health crisis in the coming years. OBJECTIVE: To investigate the
      effectiveness of combining exercise and psychotherapy in improving acute
      depressive symptoms among older adults who were receiving treatment in an
      inpatient psychiatric unit. DESIGN: Based on rolling admissions, inpatients were
      randomly assigned to 1 of 3 treatment groups. The study was blinded and
      controlled. SETTING: This study took place in inpatient psychiatric units at the
      Loma Linda University's Behavioral Medicine Center (LLUBMC) in Redlands,
      California. PARTICIPANTS: Participants were 78 inpatients, aged 50-89 y.
      INTERVENTION: Participants in the simultaneous exercise and psychotherapy (STEP)
      group (n = 26) took part in exercise and received psychotherapy for 30 min per
      session, whereas those in the TALK group (n = 26) received individual
      psychotherapy for 30 min per session. Participants in the control group (n = 26)
      served as a comparison group, receiving standard therapy. OUTCOME MEASURES: The
      effects of the interventions were determined by assessing differences from
      baseline to postintervention in the symptomatology of all 3 groups. The research
      team also administered the Behavioral and Symptom Identification Scale (BASIS-32)
      and the Geriatric Depression Scale (GDS) pre- and postintervention. RESULTS: At
      posttest, the STEP group (M = 4.24, SE = 0.62) had a better response than the
      TALK group (M = 11.34, SE = 0.62, P < .001), which in turn showed greater
      improvement than the control group (M = 14.84, SE = 0.62, P < .001). Overall,
      these results indicate that patients' posttreatment depression scores were
      significantly lower in those receiving the STEP treatment compared with those
      receiving individual psychotherapy only or standard care. CONCLUSION: A short
      term exercise program consisting of 30 min of walking in conjunction with
      individual psychotherapy was an effective intervention for depression among older
      adults in inpatient psychiatric units.

PMID- 25590293
TI  - Toward an operational model of decision making, emotional regulation, and mental
      health impact.
AB  - Current brain research increasingly reveals the underlying mechanisms and
      processes of human behavior, cognition, and emotion. In addition to being of
      interest to a wide range of scientists, educators, and professionals, as well as
      laypeople, brain-based models are of particular value in a clinical setting.
      Psychiatrists, psychologists, counselors, and other mental health professionals
      are in need of operational models that integrate recent findings in the physical,
      cognitive, and emotional domains, and offer a common language for
      interdisciplinary understanding and communication. Based on individual traits,
      predispositions, and responses to stimuli, we can begin to identify emotional and
      behavioral pathways and mental processing patterns. The purpose of this article
      is to present a brain-path activation model to understand individual differences
      in decision making and psychopathology. The first section discusses the role of
      frontal lobe electroencephalography (EEG) asymmetry, summarizes state- and trait
      based models of decision making, and provides a more complex analysis that
      supplements the traditional simple left-right brain model. Key components of the
      new model are the introduction of right hemisphere parallel and left hemisphere
      serial scanning in rendering decisions, and the proposition of pathways that
      incorporate both past experiences as well as future implications into the
      decision process. Main attributes of each decision-making mechanism are provided.
      The second section applies the model within the realm of clinical mental health
      as a tool to understand specific human behavior and pathology. Applications
      include general and chronic anxiety, depression, paranoia, risk taking, and the
      pathways employed when well-functioning operational integration is observed.
      Finally, specific applications such as meditation and mindfulness are offered to
      facilitate positive functioning. 

PMID- 25590297
TI  - The potential of minor ginsenosides isolated from the leaves of Panax ginseng as
      inhibitors of melanogenesis.
AB  - Three minor ginsenosides, namely, ginsenoside Rh6 (1), vina-ginsenoside R4 (2)
      and vina-ginsenoside R13 (3), were isolated from the leaves of hydroponic Panax
      ginseng. The chemical structures were determined based on spectroscopic methods,
      including fast atom bombardment mass spectroscopy (FAB-MS), 1D-nuclear magnetic
      resonance (NMR), 2D-NMR, and, infrared (IR) spectroscopy. The melanogenic
      inhibitory activity of compounds 1, 2 and 3 was 23.9%, 27.8% and 35.2%,
      respectively, at a concentration of 80 uM. Likewise, the three compounds showed
      inhibitory activity on body pigmentation on a zebrafish model, which is commonly
      used as a model for biomedical or cosmetic research. These results from in vitro
      and in vivo systems suggest that the three aforementioned compounds isolated from
      Panax ginseng may have potential as new skin whitening compounds. 

PMID- 25590299
TI  - Synthesis and degradation of Schiff bases containing heterocyclic pharmacophore.
AB  - This paper reports on the synthesis and characterization of two Schiff bases
      bearing 1,2,4-triazolic moieties, namely 4H-4-(2-hydroxy-benzylidene-amino)-5
      benzyl-3-mercapto-1,2,4-triazole and 4H-4-(4-nitro-benzylidene-amino)-5-benzyl-3
      mercapto-1,2,4-triazole using thin layer chromatography, melting interval,
      elemental analysis, spectroscopy and thermal stability studies. 

PMID- 25590300
TI  - The cluster [Re6Se8I6]3- induces low hemolysis of human erythrocytes in vitro:
      protective effect of albumin.
AB  - The cluster Re6Se8I63- has been shown to induce preferential cell death of a
      hepatic carcinoma cell line, thus becoming a promising anti-cancer drug. Whether
      this cluster induces acute hemolysis or if it interacts with albumin remains
      unclear. The effect of acute exposure of human red blood cells to different
      concentrations of the cluster with and without albumin is described. Red blood
      cells from healthy donors were isolated, diluted at 1% hematocrit and exposed to
      the cluster (25-150 uM) at 37  degrees C, under agitation. Hemolysis and
      morphology were analyzed at 1 and 24 h. The potential protection of 0.1% albumin
      was also evaluated. Exposition to therapeutic doses of the cluster did not induce
      acute hemolysis. Similar results were observed following 24 h of exposition, and
      albumin slightly reduced hemolysis levels. Furthermore, the cluster induced
      alteration in the morphology of red blood cells, and this was prevented by
      albumin. Together, these results indicate that the cluster Re6Se8I63- is not a
      hemolytic component and induces moderate morphological alterations of red blood
      cells at high doses, which are prevented by co-incubation with albumin. In
      conclusion, the cluster Re6Se8I63- could be intravenously administered in animals
      at therapeutic doses for in vivo studies. 

PMID- 25590298
TI  - Mechanisms and applications of interleukins in cancer immunotherapy.
AB  - Over the past years, advances in cancer immunotherapy have resulted in innovative
      and novel approaches in molecular cancer diagnostics and cancer therapeutic
      procedures. However, due to tumor heterogeneity and inter-tumoral discrepancy in
      tumor immunity, the clinical benefits are quite restricted. The goal of this
      review is to evaluate the major cytokines-interleukins involved in cancer
      immunotherapy and project their basic biochemical and clinical applications.
      Emphasis will be given to new cytokines in pre-clinical development, and
      potential directions for future investigation using cytokines. Furthermore,
      current interleukin-based approaches and clinical trial data from combination
      cancer immunotherapies will also be discussed. It appears that continuously
      increasing comprehension of cytokine-induced effects, cancer stemness,
      immunoediting, immune-surveillance as well as understanding of molecular
      interactions emerging in the tumor microenvironment and involving microRNAs,
      autophagy, epithelial-mesenchymal transition (EMT), inflammation, and DNA
      methylation processes may hold much promise in improving anti-tumor immunity. To
      this end, the emerging in-depth knowledge supports further studies on optimal
      synergistic combinations and additional adjuvant therapies to realize the full
      potential of cytokines as immunotherapeutic agents. 

PMID- 25590301
TI  - Apigenin-7-glycoside prevents LPS-induced acute lung injury via downregulation of
      oxidative enzyme expression and protein activation through inhibition of MAPK
      phosphorylation.
AB  - Apigenin-7-glycoside (AP7Glu) with multiple biological activities is a flavonoid
      that is currently prescribed to treat inflammatory diseases such as upper
      respiratory infections. Recently, several studies have shown that its anti
      inflammatory activities have been strongly linked to the inhibition of secretion
      of pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOs) and
      cyclooxygenase-2 (COX-2) induced through phosphorylation nuclear factor-kappaB
      (NF-kappaB) and mitogen-activated protein kinases (MAPK) pathways. Additionally,
      inflammation, which can decrease the activities of antioxidative enzymes (AOEs)
      is also observed in these studies. At the same time, flavonoids are reported to
      promote the activities of heme oxygenase-1 (HO-1) decreased by LPS. The purpose
      of this study was to assess these theories in a series of experiments on the
      suppressive effects of AP7Glu based on LPS-induced nitric oxide production in
      RAW264.7 macrophages in vitro and acute lung injury in mice in vivo. After six
      hours of lipopolysaccharide (LPS) stimulation, pulmonary pathological,
      myeloperoxidase (MPO) activity, total polymorphonuclear leukocytes (PMN) cells,
      cytokines in bronchoalveolar lavage fluid (BALF) and AOEs, are all affected and
      changed. Meanwhile, our data revealed that AP7Glu not only did significantly
      inhibit the LPS-enhanced inflammatory activity in lung, but also exhibited anti
      inflammatory effect through the MAPK and inhibitor NF-kappaB (IkappaB) pathways. 

PMID- 25590302
TI  - Novel transcription factor variants through RNA-sequencing: the importance of
      being "alternative".
AB  - Alternative splicing is a pervasive mechanism of RNA maturation in higher
      eukaryotes, which increases proteomic diversity and biological complexity. It has
      a key regulatory role in several physiological and pathological states. The
      diffusion of Next Generation Sequencing, particularly of RNA-Sequencing, has
      exponentially empowered the identification of novel transcripts revealing that
      more than 95% of human genes undergo alternative splicing. The highest rate of
      alternative splicing occurs in transcription factors encoding genes, mostly in
      Kruppel-associated box domains of zinc finger proteins. Since these molecules are
      responsible for gene expression, alternative splicing is a crucial mechanism to
      "regulate the regulators". Indeed, different transcription factors isoforms may
      have different or even opposite functions. In this work, through a targeted re
      analysis of our previously published RNA-Sequencing datasets, we identified nine
      novel transcripts in seven transcription factors genes. In silico analysis,
      combined with RT-PCR, cloning and Sanger sequencing, allowed us to experimentally
      validate these new variants. Through computational approaches we also predicted
      their novel structural and functional properties. Our findings indicate that
      alternative splicing is a major determinant of transcription factor diversity,
      confirming that accurate analysis of RNA-Sequencing data can reliably lead to the
      identification of novel transcripts, with potentially new functions. 

PMID- 25590304
TI  - Serum level of interleukin-21 is elevated in chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease of the
      sinuses and mucosa with unclear pathogenesis. Interleukin (IL)-21 is mainly
      expressed in activated cluster of differentiation (CD)4(+) T cells and has potent
      regulatory effects on the immune system. OBJECTIVE: This study is to determine
      whether IL-21 in the blood is correlated with CRS. METHODS: The blood samples
      from CRS patients and normal controls were analyzed in correlation with clinical
      features. The eosinophil percentage was counted, and serum levels of total
      immunoglobulin E (IgE) and IL-21 were analyzed by enzyme-linked immunosorbent
      assay (ELISA). In addition, IL-21 and interferon (IFN)-gamma secreted from
      stimulated peripheral blood mononuclear cells (PBMCs) were measured by ELISA, and
      their mRNA expression levels were analyzed by real-time quantitative polymerase
      chain reaction (RT-qPCR). Disease severity was scored based on computed
      tomography (CT) scan, nasal endoscopy, and global osteitis scoring scale (GOSS).
      RESULTS: A total of 55 CRS and 37 healthy subjects were recruited. The average
      levels of serum total IgE were 20 kU/L in normal group, 290 kU/L in CRS with
      nasal polys (CRSwNP), and 187 kU/L in CRS without nasal polys (CRSsNP). IL-21
      levels were 28 pg/mL in normal group, 54 pg/mL in CRSwNP, and 71 pg/mL in CRSsNP.
      Both IgE and IL-21 were significantly elevated in both CRS patient subgroups.
      However, no significant difference was found between these two patient subgroups.
      The serum IL-21 levels correlated well with the disease severity in the patients.
      In addition, the secreted IL-21 was enhanced significantly in the patient's PBMCs
      stimulated by phytohemagglutin (PHA). CONCLUSION: IL-21 could be a target for
      diagnosis and treatment of CRS.

PMID- 25590305
TI  - Editorial: Advances in the diagnosis and treatment of patients with chronic
      rhinosinusitis and allergy.

PMID- 25590303
TI  - Mechanisms and implications of dual-acting methotrexate in folate-targeted
      nanotherapeutic delivery.
AB  - The rational design of a nanoplatform in drug delivery plays a crucial role in
      determining its targeting specificity and efficacy in vivo. A conventional
      approach relies on the surface conjugation of a nanometer-sized particle with two
      functionally distinct types of molecules, one as a targeting ligand, and the
      other as a therapeutic agent to be delivered to the diseased cell. However, an
      alternative simplified approach can be used, in which a single type of molecule
      displaying dual function as both a targeting ligand and therapeutic agent is
      conjugated to the nanoparticle. In this review, we evaluate the validity of this
      new strategy by using methotrexate, which displays multifunctional mechanisms of
      action. Methotrexate binds to the folate receptor, a surface biomarker frequently
      overexpressed in tumor cells, and also inhibits dihydrofolate reductase, an
      enzyme critical for cell survival and division. Thus we describe a series of
      fifth generation poly(amido amine) dendrimers conjugated with methotrexate, and
      discuss several lines of evidence supporting the efficacy of this new platform
      strategy based on surface plasmon resonance spectroscopy, enzyme activity assays,
      and cell-based studies with folate receptor (+) KB cancer cells. 

PMID- 25590306
TI  - Intranasal steroids and the myth of mucosal atrophy: a systematic review of
      original histological assessments.
AB  - BACKGROUND: Intranasal corticosteroids (INCSs) are well established in the
      treatment of allergic rhinitis, chronic rhinosinusitis, and nasal polyposis.
      Although reversible atrophy of keratinized skin is seen with corticosteroids, the
      respiratory mucosa is histologically very different and but concerns remain among
      patients and some health-care professionals over local side effects on nasal
      respiratory mucosa. A systematic review and meta-analysis were performed of the
      available evidence for nasal mucosal atrophy as an adverse effect of INCSs in
      patients with sinonasal disease. METHODS: A systematic search of Embase (1974-)
      and Medline (1946-) databases to September 27, 2013 was performed. Inclusion
      criteria selected any study where the histopathology of nasal mucosa was assessed
      in patients with sinonasal disease using intranasally administered
      corticosteroids with or without a control group. RESULTS: Twenty-three hundred
      sixty-four publications were retrieved with a subsequent full text review of 149
      publications for 34 articles that met the selection criteria. These articles
      included 11 randomized controlled trials, 5 cohorts, and 20 case series. Duration
      of treatment varied from 5 days to 5.5 years. "Mucosal atrophy" as an outcome was
      reported in 17 studies. The definition of "mucosal atrophy" was highly variable
      with a definition given in only 10 studies. One hundred thirty-six patients were
      represented in controlled studies of atrophy with only one study reporting the
      event in both groups with an odds ratio of "mucosal atrophy" at 0.51 (95% CI,
      0.09-3.11; p = 0.47). CONCLUSION: The concept of nasal mucosal atrophy is poorly
      defined and there is no histological evidence for deleterious effects from INCS
      use on human nasal mucosa.

PMID- 25590307
TI  - Septic cavernous sinus thrombosis secondary to acute bacterial sinusitis: a
      retrospective study of seven cases.
AB  - BACKGROUND: Septic cavernous sinus thrombosis (SCST) is a rare but severe
      complication of acute bacterial sinusitis. Evaluations of advances in imaging
      techniques as well as in medical and surgical treatment are hampered by the lack
      of recent studies. OBJECTIVE: We aim to report our experience in the management
      of SCST in patients with acute bacterial sphenoid sinusitis over the past 10
      years and to discuss the initial work-up and treatment strategies. METHODS: We
      performed a retrospective study of patients admitted for SCST related to acute
      sinusitis at a tertiary care center between 2003 and 2013. Clinical charts were
      reviewed for demographics, clinical presentations, imaging and microbiologic
      findings, medical and surgical treatments, and outcomes. RESULTS: Seven patients
      were treated for SCST. Sphenoid sinus was involved in all cases. The most
      frequent presenting signs included headache (100%), cranial nerve impairment
      (86%), fever (71%), and orbital symptoms (71%). Diagnosis was confirmed by a
      cerebral contrast-enhanced CT scan in all cases. Four patients (57%) had an
      additional intracranial complication. The average time between clinical onset and
      diagnosis was 13.7 days. All patients were treated by high-dose i.v. antibiotics,
      anticoagulation therapy, and surgical endoscopic drainage of the infected
      sinuses. This treatment strategy resulted in a mortality rate of 0%, but four out
      of the seven patients developed transient or permanent neurologic deficits,
      including one with permanent unilateral visual loss. CONCLUSION: The combination
      of high-dose i.v. antibiotics, anticoagulation therapy, and endoscopic drainage
      of the infected paranasal sinus is an effective strategy for the treatment of
      SCST, but long-term sequelae remain frequent.

PMID- 25590308
TI  - Squeeze bottle versus saline spray after endoscopic sinus surgery for chronic
      rhinosinusitis: a pilot multicentre trial.
AB  - BACKGROUND: There is a need for controlled trials to guide the perioperative
      management of patients undergoing endoscopic sinus surgery (ESS). The authors
      performed a pilot multicenter trial to compare two types of saline delivery
      devices in this population. METHODS: Patients were randomized to high volume
      saline irrigation with a squeeze bottle and low volume saline spray after ESS in
      patients with chronic rhinosinusitis (CRS). Surgeons were blinded to treatment,
      and one-month postoperative scores for sinonasal outcomes [Sinonasal Outcome Test
      22 (SNOT-22)] scale, nasal and sinus symptom score (NSS), and perioperative sinus
      endoscopy (POSE) scale were compared with preoperative scores. RESULTS: Nine
      centers provided data for 86 patients. All three outcomes measures improved
      significantly for both groups. Saline spray: SNOT-22 48.8 versus. 23.7, treatment
      effect 25.1 (95% confidence interval [CI], 17.9-32.2), POSE 21.1 versus. 8.4,
      treatment effect 12.7 (95% CI, 9.2-16.1), and NSS 8.2 versus 5.0, treatment
      effect 3.1 (95% CI, 1.4-4.9) pre- and postoperatively, respectively (all p <
      0.0001). Squeeze bottle: SNOT-22 49.5 versus 23.6, treatment effect 25.9 (95% CI,
      20.3-31.6), POSE 18.6 versus 9.2, treatment effect 9.3, (95% CI 6.7-12.0), and
      NSS 9.0 versus 5.7, treatment effect 3.3 (95% CI, 2.3-4.3) pre- and
      postoperatively, respectively (all p < 0.0001). Analysis of variance did not
      identify a difference between the two treatment groups. Subgroup analysis based
      on preoperative disease severity did not change the nonassociation of saline
      bottle with outcome measures. Post hoc sample size calculation determined that
      176 patients is required to detect an 8.9-point difference in SNOT-22 scores.
      CONCLUSION: In this pilot multicenter trial examining patients with chronic
      rhinosinusitis undergoing ESS, both squeeze bottle and saline spray showed
      significant improvement in SNOT-22, POSE, and NSS scores at one-month
      postoperatively. Because the study was nonpowered, we cannot rule out a potential
      difference between the two treatment groups.

PMID- 25590309
TI  - Expression and regulation of interleukin-9 in chronic rhinosinusitis.
AB  - BACKGROUND: The pathogenesis of human chronic rhinosinusitis (CRS) remains
      controversial. Recent evidence has suggested that interleukin (IL)-9 is vital in
      eliciting inflammatory response, stimulating cell proliferation and preventing
      apoptosis, through binding to the IL-9 receptor (IL-9R). However, little is known
      about the roles of both molecules in the etiology of CRS. Therefore, this study
      aimed to assess IL-9 and IL-9R expression and determine their roles in the
      pathophysiology of CRS. METHODS: Immunohistochemistry was used to assess IL-9 and
      IL-9R immunolabeling. In addition, Western blotting and real-time polymerase
      chain reaction (PCR) were used for IL-9 and IL-9R protein and mRNA level
      quantitation, respectively, in CRS and control subjects. Furthermore, the effects
      of various stimulators at different concentrations and time on IL-9 were
      evaluated using nasal explant cultures. RESULTS: IL-9 and IL-9R were
      overexpressed in CRS, especially in CRS with nasal polyps. Interestingly, IL-9
      expression was closely related to that of IL-9R. In addition, IL-9 mRNA levels
      were increased by treatment with IL-4, IL-17A, IL-1beta, and the IL-4 and
      transforming growth factor (TGF) beta1 combination, but suppressed by interferon
      gamma and IL-27. CONCLUSION: IL-9 and IL-9R were overexpressed in CRS at both
      protein and mRNA levels. In addition, IL-4, IL-17A, IL-1beta, and the IL-4 and
      TGF-beta1 combination contributed to increased IL-9 levels. Our findings indicate
      that IL-9 may play a proinflammatory role after IL-9R binding to induce mucosal
      epithelial cell growth, gland epithelial cell proliferation, and inflammatory
      cell infiltration in CRS. Future studies are required to further define the role
      of IL-9 in CRS etiology.

PMID- 25590310
TI  - The seasonality of respiratory viruses in patients with chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is a common illness, yet little is known
      about its pathogenesis, including the role played by respiratory viruses.
      METHODS: A transversal prospective study was conducted to analyze the seasonality
      of CRS using real-time polymerase chain reaction to detect respiratory virus
      genomes in secretions and tissue samples from patients with CRS with and without
      nasal polyps. RESULTS: The frequency of viral detection was 41% (31/75). The
      respiratory virus most frequently detected was human rhinovirus, found in 18
      patients (24%), followed by human metapneumovirus, human enterovirus, human
      respiratory sincicial virus, human adenovirus, human bocavirus, human
      coronavirus, and human influenza virus, detected in 12 (16%), five (6.6%), four
      (5.3%), four (5.3%), two (2.6%), two (2.6%), and one (1.3%) patient(s),
      respectively. Although none of the patients presented symptoms when the samples
      were collected, there was a peak in detection of the most prevalent virus in the
      autumn and winter seasons of both years, similar to the pattern that occurs in
      acute conditions. CONCLUSIONS: The pattern of respiratory virus seasonality found
      in nasal mucosa, polyps, and paranasal sinus samples in patients with CRS
      reinforces the possibility of asymptomatic respiratory viral infections.

PMID- 25590311
TI  - Staphylococcus aureus biofilms induce apoptosis and expression of interferon
      gamma, interleukin-10, and interleukin-17A on human sinonasal explants.
AB  - BACKGROUND: Staphylococcus aureus is one of the most common bacteria associated
      with chronic rhinosinusitis (CRS). Although S. aureus biofilms have been
      correlated with disease severity in CRS, little is known about the initial immune
      response that biofilms induce in the sinonasal mucosa. OBJECTIVE: The aim of this
      study was to evaluate the innate immune response (in terms of cytokines) of
      nondiseased human sinonasal tissue to S. aureus biofilms. METHODS: Full-thickness
      sinonasal explant cultures (n = 7 donors) were challenged with established S.
      aureus biofilms for 24 hours. The expression profiles of 17 cytokines were
      measured using multiplex analysis, real-time quantitative reverse transcription
      polymerase chain reaction, and immunohistochemistry. Differences in expression
      were evaluated using Student's t-test. RESULTS: Interleukin (IL)-1beta, IL-10,
      TNF, IL-17A, and interferon (IFN)-gamma were up-regulated at the RNA and protein
      levels in biofilm-treated tissues compared with controls. Elevation of caspase-3
      in biofilm-treated samples indicates S. aureus biofilms induce apoptosis on the
      sinonasal mucosa. CONCLUSION: S. aureus biofilms induced apoptosis and a
      predominant proinflammatory immune response on normal sinonasal mucosal explants.
      This immune response appeared to be triggered by intrinsic bacterial elements but
      also by components of the biofilm matrix. Live biofilms were present on the
      mucosa at the end of the challenge, suggesting an inability of the induced immune
      response to eliminate the S. aureus biofilms.

PMID- 25590312
TI  - Prevalence of nasal polyps and its risk factors: Korean National Health and
      Nutrition Examination Survey 2009-2011.
AB  - BACKGROUND: Although nasal polyps (NPs) are thought to be a common
      otorhinolaryngologic disease, there have been few population-based epidemiologic
      studies on the prevalence of NPs. The aim of this study is to evaluate the
      prevalence of NPs and the risk factors in the general Korean population. METHODS:
      The data were obtained from the Korea National Health and Nutrition Examination
      Survey (KNHANES) (2009-2011), which was a cross-sectional survey of
      noninstitutionalized populations all around the country (n = 28,009). Among them,
      19,152 participants (age more than or equal to 20 years) completed medical
      interviews, physical examinations and endoscopic examination. Analyses were
      performed using a complex sample design to identify the prevalence and its risk
      factors. RESULTS: The weighted prevalence of NPs was 2.5%. The increased
      prevalence was associated with increasing age. In the multivariate analyses, male
      sex [adjusted odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.25-2.26],
      low education level (adjusted OR = 1.57, CI = 1.16-2.13), obesity (adjusted OR =
      1.49, CI = 1.19-1.87), asthma (adjusted OR = 1.80, CI = 1.24-2.62), and thyroid
      cancer (adjusted OR = 2.98, CI = 1.26-7.09) were associated with NPs. Among those
      with NPs, the proportion of symptomatic NPs was 34.4% and asthma was the only
      significant associated risk factor. CONCLUSION: The prevalence of NPs in the
      Korean general population was not low despite advances in medical and surgical
      treatment and two thirds of the subjects with NPs were asymptomatic. Further
      investigation is needed to exhibit the causal relationship between the associated
      risk factors identified and NPs.

PMID- 25590313
TI  - Initial investigation of small colony variants of Staphylococcus aureus in
      chronic rhinosinusitis.
AB  - BACKGROUND: Small colony variants (SCVs) are a metabolically inactive form of
      bacteria that can be difficult to eradicate. To examine whether SCVs contribute
      to Staphylococcus aureus persistence in chronic rhinosinusitis (CRS), we compared
      the prevalence of S. aureus SCVs in CRS patients and healthy controls. METHODS:
      Endoscopically guided middle meatus samples were collected from 23 CRS patients
      and 12 controls. Samples were cultured and screened for the presence of
      phenotypically small colonies. Candidate SCV isolates were classified by 16S rRNA
      gene sequencing. To further characterize the capacity of S. aureus isolates to
      form SCVs when stressed, colonies underwent a gentamicin exposure assay. RESULTS:
      Among CRS patient samples, 15 were culture positive for S. aureus (65.2%), and of
      those, two grew putative SCVs on selective media (8.7%). However, neither was
      genetically confirmed to be S. aureus upon sequencing. In healthy controls, eight
      specimens were culture positive for S. aureus (66.7%), and of these, two grew
      putative S. aureus SCVs on selective media (16.7%); but again, neither was
      confirmed to be S. aureus by 16S analysis. None of the four patients colonized
      with SCVs had evidence of sinonasal disease at a mean follow-up of eight months.
      S. aureus isolates from CRS patients and controls were equally likely to form
      SCVs with gentamicin exposure. CONCLUSION: S. aureus SCVs were not associated
      with CRS in the current study. Their role in refractory CRS remains theoretical,
      and further research is warranted to determine whether S. aureus SCVs may reside
      in the intracellular compartment.

PMID- 25590314
TI  - Therapeutic effects of intranasal cyclosporine for eosinophilic rhinosinusitis
      with nasal polyps in a mouse model.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a
      principally type 2 T helper cell (Th2)-mediated inflammatory disease. Systemic
      corticosteroids currently represent the most effective treatment for CRSwNP, but
      their long-term use is constrained due to their detrimental side effects. Long
      term use of topical steroids is safe, but their efficacy is often limited.
      Topical cyclosporine has proven to be safe and effective for Th2-mediated
      diseases such as allergic conjunctivitis. OBJECTIVE: It was hypothesized that
      topical cyclosporine would be an effective novel drug for the treatment of
      CRSwNP; its therapeutic efficacy was assessed using a previously established
      mouse model. METHODS: After induction of eosinophilic CRSwNP in four-week-old
      BALB/c mice according to previous protocols, the therapeutic effects of
      intranasal cyclosporine were evaluated and compared with those of triamcinolone
      acetonide (TAC). Histopathologic changes were evaluated using hematoxylin and
      eosin for polyp formation and Sirius red staining for eosinophilic infiltration.
      The production of cytokines in sinonasal tissues, including tumor necrosis factor
      (TNF), interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-5, IL-13, and IL-17A,
      was measured using a cytometric bead array. RESULTS: The number of polyp-like
      lesions was reduced significantly only by systemic TAC, but the degree of
      eosinophilic infiltration was decreased significantly by topical cyclosporine,
      the potency of which was similar to that of topical or systemic TAC. Except for
      IFN-gamma, the majority of measured cytokines were reduced significantly by
      topical cyclosporine, although their effects on IL-2 and IL-13 were less potent
      than those of systemic TAC. CONCLUSION: Topical cyclosporine might be an
      effective drug for the management of CRSwNP.

PMID- 25590315
TI  - A novel method for comparison of tissue fibrosis after inferior turbinate
      surgery: ultrasound elastography.
AB  - BACKGROUND: Ultrasound (US) elastography has been widely used for thyroid, liver,
      and lymph nodes as a research tool in the current medical practice. It has been
      described in the inferior turbinates and validated as a reliable, reproducible,
      noninvasive, and objective method that can detect the fibrosis-related tissue
      strain. There is no previous study that investigated the amount of fibrosis
      induced by radiofrequency and bipolar electrocautery in the inferior turbinates
      in a noninvasive and objective manner. The aim of this study was to assess the
      amount of inferior turbinate soft tissue fibrosis that was induced by
      radiofrequency ablation (RFA) and submucosal bipolar diathermy (SBD) by US
      elastography. METHODS: Thirty-eight inferior turbinates of 19 patients were
      included. RFA was applied to 18 inferior turbinates (group 1) and SBD was applied
      to 20 inferior turbinates (group 2). US elastography and visual analog scale
      (VAS) assessments were performed on all patients preoperatively and 6 months
      postoperatively. RESULTS: Preoperative mean US elastography scores in groups 1
      and 2 were 2.55 +/- 0.78 m/s and 2.56 +/- 0.49 m/s, respectively (p < 0.05).
      Postoperative mean US elastography scores in groups 1 and 2 were 2.91 +/- 1.03
      m/s and 3.41 +/- 0.86 m/s, respectively (p < 0.05). Preoperative mean VAS scores
      in groups 1 and 2 were 2.78 +/- 0.94 and 2.50 +/- 1.15, respectively.
      Postoperative mean VAS scores in groups 1 and 2 were 6.61 +/- 1.61 and 6.10 +/-
      1.4, respectively (p < 0.05). Correlation of US elastography and VAS scores was
      insignificant (p > 0.05). CONCLUSION: Both RFA and SBD of the inferior turbinates
      were effective in inducing scar tissue and, eventually, fibrosis in the soft
      tissue of inferior turbinates. Cauterization has been found to cause
      significantly higher amounts of fibrosis than radiofrequency; however, it did not
      reflect the comparable clinical outcome. This is the first study that objectively
      and noninvasively evaluates the targeted tissue fibrosis of the inferior
      turbinate surgeries by the novel inferior turbinate US elastography.

PMID- 25590317
TI  - Management of sinonasal mucosal melanomas and comparison of classification
      staging systems.
AB  - OBJECTIVE: The aim of this study was to describe treatment results in patients
      with sinonasal mucosal melanomas (SMMs) and to compare three different
      classification staging systems. MATERIALS AND METHODS: From 1988 to 2013, we
      performed a retrospective study of 20 patients with primary sinonasal melanomas.
      The median age at diagnosis was 71 years. There were 10 males and 10 females.
      RESULTS: Nine SMMs (45%) were originated in the ethmoidal sinus complex, four
      (20%) in the inferior turbinate, three (15%) in the nasal septum, two (10%) in
      the maxillary sinus, and two (10%) in the nasal vestibule. Local recurrence was
      diagnosed in eight patients (40%), and six out of 20 patients (30%) developed
      distant metastasis during the course of their disease. The adjusted survival
      rates at three and five years were 47% and 34%, respectively. The adjusted three
      year survival rate according to the sinonasal staging system 7th edition for SMM
      (TNM-SMM) was 60% in T3 stage, 50% in T4a stage, and 34% in T4b stage (p = 0.05).
      According to Thompson's staging system, survival was 33% for group one, 58% for
      group two, and 0% for group three (p = 0.006). With the sinonasal staging system
      7th edition for carcinoma (TNM-CAR) survival was 33% in T1, 100% in T2 and T3, 0%
      in T4a, and 34% in T4b (p = 0.006). CONCLUSIONS: Our experience confirms the
      distribution of patients according to survival rates was better with the TNM-SMM
      than with Thompson's or the TNM-CAR systems.

PMID- 25590318
TI  - State of the Art: Medical treatment of aspirin exacerbated respiratory disease
      (AERD).
AB  - Aspirin exacerbated respiratory disease (AERD) is characterized as adult onset
      asthma, nasal polyps, chronic rhinosinusitis, and hypersensitivity to a
      cyclooxygenase-1 (COX-1) inhibitor, viz aspirin or nonsteroidal antiinflammatory
      drugs (NSAIDs). The method for diagnosing AERD is with aspirin challenge, and
      treatment includes aspirin desensitization followed by continued daily aspirin.
      Although oral challenge has been the mainstay in the United States, lysyl-aspirin
      has been validated as a diagnostic tool for aspirin-sensitive asthma and will be
      discussed further in this article. The challenges with aspirin therapy
      surrounding endoscopy and perioperative aspirin therapy will be discussed.
      Additionally, daily aspirin therapy is not for everyone. Aspirin is relatively
      contraindicated in those with a history of gastrointestinal bleed and an absolute
      contraindication in pregnancy. Aspirin desensitization and subsequent treatment
      has been shown to be highly effective for AERD. 

PMID- 25590319
TI  - Dementia is associated with chronic rhinosinusitis: a population-based case
      controlled study.
AB  - BACKGROUND: Cardiovascular diseases are reported to be associated with both
      chronic rhinosinusitis (CRS) and dementia. Nevertheless, whether dementia is
      associated with CRS is still unknown. In the present study, we explored the
      association between dementia with prior CRS using a population-based data set.
      METHODS: This study used the Taiwan Longitudinal Health Insurance Database 2000
      as the source of data for a case-control study. We included 8768 subjects with
      dementia as cases and 8768 age- and sex-matched subjects as controls. We
      identified cases who had received a diagnosis of CRS before having received a
      diagnosis of dementia. Conditional logistic regression analyses were performed to
      examine the association of dementia with previously diagnosed CRS. RESULTS:
      Results showed that of all sampled subjects, 875 (5.0%) had been previously
      diagnosed with CRS. A chi-squared test showed that there was a significant
      difference in the prevalences of prior CRS between cases and controls (6.0%
      versus 4.0%; p < 0.001). The adjusted odds ratio (OR) of prior CRS for subjects
      with dementia was 1.44 (95% CI, 1.25~1.66) compared with controls. Furthermore,
      compared with controls, the OR of prior CRS was similar for subjects with
      dementia for both sexes (the OR for male subjects was 1.48 and OR for female
      subjects was 1.41). CONCLUSION: We concluded that subjects with dementia had a
      higher odds of having had prior CRS than controls. This study implies a potential
      association between CRS and dementia.

PMID- 25590316
TI  - Factors driving the aspirin exacerbated respiratory disease phenotype.
AB  - BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is explained in part
      by overexpression of 5-lipoxygenase and leukotriene C4 synthase (LTC4S),
      resulting in constitutive overproduction of cysteinyl leukotrienes (CysLTs) and
      driving the surge in CysLT production that occurs with aspirin ingestion.
      Similarly, AERD is characterized by the overexpression of CysLT receptors.
      Increased levels of both interleukin (IL)-4 and interferon (IFN)-gamma are
      present in the tissue of AERD subjects. Previous studies demonstrated that IL-4
      is primarily responsible for the up-regulation of LTC4S by mast cells. METHODS:
      Literature review. RESULTS: Our previous studies demonstrated that IFN-gamma, but
      not IL-4, drives this process in eosinophils. These published studies also extend
      to both IL-4 and IFN-gamma the ability to up-regulate CysLT receptors.
      Prostaglandin E2 (PGE2) acts to prevent CysLT secretion by inhibiting mast cell
      and eosinophil activation. PGE2 concentrations are reduced in AERD, and our
      published studies confirm that this reflects diminished expression of
      cyclooxygenase (COX)-2. A process again that is driven by IL-4. Thus, IL-4 and
      IFN-gamma together play an important pathogenic role in generating the phenotype
      of AERD. Finally, induction of LTC4S and CysLT1 receptors by IL-4 reflects in
      part the IL-4-mediated activation of signal transducer and activator of
      transcription 6 (STAT6). Our previous studies demonstrated that aspirin blocks
      trafficking of STAT6 into the nucleus and thereby prevents IL-4-mediated
      induction of these transcripts, thereby suggesting a modality by which aspirin
      desensitization could provide therapeutic benefit for AERD patients. CONCLUSION:
      This review will examine the evidence supporting this model.

PMID- 25590320
TI  - Prognostic factors for survival in patients with acute invasive fungal
      rhinosinusitis.
AB  - BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is an aggressive
      opportunistic infection with a high mortality rate. There are few reports that
      demonstrate an improvement in the overall prognosis. Furthermore, definite
      prognostic factors related to patient survival remain unclear. OBJECTIVE: The
      objective of this study was to evaluate the various clinical factors related to
      survival of patients with AIFR. METHODS: This is a retrospective case series with
      patients treated for AIFR between 1997 and 2013. A total of 45 patients with AIFR
      were enrolled for analysis. We evaluated demographics, clinical characteristics,
      and disease course. RESULTS: Mean age of patients was 59.6 years. AIFR developed
      most commonly in patients with immunocompromised host, such as diabetes (n = 23)
      or hematologic malignancy (n = 17). There were two main genera of fungus,
      Aspergillus (n = 30) and Mucor (n = 14). Headache, cranial neuropathy, visual
      loss, and orbital pain were the most common presenting symptoms. Overall survival
      was 53%. Underlying hematologic malignancy and diabetes were significantly
      associated with overall survival, and accompanying severe neutropenia and
      elevated C-reactive protein (CRP) were also related to poor prognosis. Initial
      presentation with facial swelling, involvement of nasal septum, or shorter
      symptom duration was also associated with survival reduction. Multivariate
      analysis revealed that CRP more than 5.50 mg/dL (Hazard ratio [HR], 9.04; p =
      .003) was an independent prognostic factor in patients with AIFR. CONCLUSIONS:
      Overall survival rate remained approximately 50% in patients with AIFR. The
      prognosis of AIFR is significantly influenced by underlying diseases,
      accompanying neutropenia, CRP levels, symptom duration, involvement of septum,
      and the presence of facial swelling. Elevation of CRP, in particular, was an
      independent predictor of poor outcomes and should be monitored appropriately.

PMID- 25590321
TI  - Does atopy influence the effectiveness of treatment of adenoid hypertrophy with
      mometasone furoate?
AB  - BACKGROUND: The effect of topical mometasone for adenoid hypertrophy treatment is
      well established. Nevertheless, the influence of atopy on this treatment remains
      ill defined. OBJECTIVE: This study aims to compare the effects of topical
      mometasone furoate treatment on the adenoid tissue between atopic and nonatopic
      children. METHODS: Fifty-one children with obstructive respiratory complaints
      underwent a semistructured clinical questionnaire on nasal symptoms, prick test,
      and nasoendoscopy. Nasoendoscopic images were digitalized, and both adenoid and
      nasopharyngeal areas were measured in pixels; the relative adenoid/nasopharyngeal
      area was calculated. Patients were initially treated for 40 days with nasal
      saline solution. In a subsequent 40-day period, topical mometasone furoate (total
      dose, 100 MUg/day) was used. RESULTS: Topical mometasone significantly improved
      nasal obstruction, snoring, and apnea and also significantly reduced the adenoid
      tissue area related to the nasopharynx (p < 0.0001). Treatment with this
      glucocorticoid was not influenced by atopy, neither for symptoms nor for adenoid
      area. CONCLUSION: Topical mometasone furoate significantly reduced the adenoid
      tissue area and led to a supplementary improvement of nasal symptoms. This
      improvement was similar for atopic and nonatopic patients.

PMID- 25590322
TI  - Acupuncture for the treatment of allergic rhinitis: a systematic review and meta
      analysis.
AB  - BACKGROUND: Because acupuncture may modulate the immune system, it has been
      proposed as a useful treatment for patients with allergic rhinitis (AR). Here, we
      assessed the evidence for the clinical efficacy of acupuncture for the management
      of AR patients by performing a systematic review and meta-analysis of the
      published literatures. METHODS: By searching PubMed, EMBASE, the Cochrane
      clinical trials database, and the China National Knowledge Infrastructure from
      1980 through July 11, 2013, we collected and analyzed the randomized controlled
      trials (RCTs) of acupuncture for the treatment of AR patients to assess its
      efficacy and safety. RESULTS: Thirteen full papers that met our inclusion
      criteria were included, and a total of 2365 participants, including 1126 as
      treatment group and 1239 as control group, were enrolled. Compared with control
      group, acupuncture treatment group exerted a significant reduction in nasal
      symptom scores (weighted mean difference [WMD]: -4.42, 95% confidence interval
      [CI]: -8.42 to -0.43, p = 0.03), medication scores (WMD: 1.39, 95% CI: -2.18 to 
      0.61, p = .0005), and serum IgE (WMD: -75.00, 95% CI: -91.17 to -58.83, p <
      0.00001). Data relating to Rhinitis Quality of Life Questionnaire (RQLQ) and 36
      Item Short-Form (SF-36) component score in included studies were analyzed, which
      ultimately point to the efficacy of acupuncture treatment in improving quality of
      life in AR patients. No fatal events were reported in any of the included
      studies, and no serious systemic reaction, which needed treatment in the
      hospital, was related to the acupuncture treatment. CONCLUSION: Our meta-analysis
      suggests that that acupuncture could be a safe and valid treatment option for AR
      patients.

PMID- 25590323
TI  - Endoscopic dacryocystorhinostomy with silicone, polypropylene, and T-tube stents;
      randomized controlled trial of efficacy and safety.
AB  - OBJECTIVE: To compare the efficacy and safety of endoscopic dacryocystorhinostomy
      (En-DCR) with different stent materials for lacrimal sac intubation in primary
      nasolacrimal ductal obstructions. STUDY DESIGN: Randomized controlled study with
      three parallel groups. Level of evidence is 1b. METHODS: A total of 91 patients
      (five bilateral) with primary nasolacrimal duct obstruction (NLDO) at a tertiary
      referral center scheduled for En-DCR were to allocated into three stent groups
      with a sealed envelope and were randomized into three treatments: silicone,
      Prolene (polypropylene), and otologic T-tube. Ophthalmology and otolaryngology
      clinics evaluated the patients preoperatively and postoperatively with
      endoscopes, lacrimal system syringing, and dacryocystography. The success of the
      stents was evaluated 12 months after surgery with symptom relief and ostial
      patency. Complications were also noted. RESULTS: The overall success rate of the
      En-DCR in the stent groups was 78.1% (75/96); specifically, 87.5% (28/32) with
      silicone, 84.4% (27/32) with Prolene, and 62.5% (20/32) with T-tube. The efficacy
      of the procedures with the T-tube was significantly lower than that of the
      Prolene and silicone (p = .031, chi(2) test). There were no significant
      differences between the silicone and Prolene (p = .718, chi(2) test). Prolene was
      found to be related with orbital complications. Spontaneous loss is a particular
      complication of otologic T-tube and highly portends to failure. CONCLUSIONS: The
      results of our study suggest that efficacy, defined as anatomic and functional
      success, is equally high for silicone and Prolene stents and lower for otologic T
      tube in En-DCR.

PMID- 25590324
TI  - Do sinus computed tomography findings predict olfactory dysfunction and its
      postoperative recovery in chronic rhinosinusitis patients?
AB  - BACKGROUND: Olfactory dysfunction secondary to chronic rhinosinusitis (CRS) is a
      mixed disorder of conductive and sensorineural olfactory impairment. Although
      endoscopic sinus surgery has some beneficial effects on olfaction, the outcomes
      are challenging to predict. The aim of this study was to assess the olfactory
      outcomes after surgery, to investigate the correlation between the severity of
      regional computed tomography (CT) findings and olfactory performance, and to
      identify the predictors of postoperative outcomes based on unilateral olfactory
      threshold analysis. METHODS: This study included 167 CRS nostrils of 97 patients
      with/without polyps (68/99 nostrils) undergoing sinus surgery between January
      2007 and December 2011. Olfactory function was evaluated using the butanol
      threshold test (BTT) before and 6 months after surgery. Clinical and nasal
      factors from sinus CT scan (sinuses, ostiomeatal complex, olfactory cleft [OC],
      nasal polyps, and unilateral Lund-Mackay CT score) were analyzed to correlate
      them with pre- and postoperative olfactory performances. RESULTS: Eighty-two
      percent of the CRS nostrils had anosmia or hyposmia. After surgery, 42% of them
      showed an improvement in BTT score. Despite improvement, most of the subjects
      remained with residual hyposmia. The BTT scores deteriorated after surgery in 23%
      of the total subjects. The disease severity of the OC, posterior ethmoid, and
      frontal sinus were the significant risk factors for CRS-related anosmia. The
      strongest risk factor for anosmia was totally obstructed OC (odds ratio [OR],
      16.56; 95% CI, 4.31-63.71; p = 0.000). The nostrils with anosmia or partly
      opacified anterior ethmoid benefited from surgery with respect to olfaction.
      CONCLUSION: Our results can give support to the combined use of the butanol
      threshold and sinonasal CT findings in the evaluation of olfaction in CRS
      patients and help us counsel the patients about the likelihood of postoperative
      olfactory recovery.

PMID- 25590325
TI  - Spontaneous CSF rhinorrhea: prevalence of multiple simultaneous skull base
      defects.
AB  - BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leaks are caused by
      intracranial hypertension. Given this underlying etiology, patients may be at
      risk for developing multiple skull base defects. OBJECTIVE: The purpose of our
      study is to present the prevalence of multiple simultaneous skull base defects in
      patients with spontaneous CSF rhinorrhea. METHODS: We performed a retrospective
      chart review in a tertiary care practice of 44 consecutive patients with
      spontaneous CSF rhinorrhea who underwent endoscopic repair by the senior author
      (R.R.C.) to determine the prevalence of having multiple simultaneous skull base
      defects identified at the time of surgery. We defined this as two or more bony
      defects identified endoscopically with intact intervening bone with or without
      soft tissue prolapse into the nasal cavity or paranasal sinus cavity. RESULTS:
      Eight of 44 patients (18.2%) were found to have multiple simultaneous skull base
      defects. The average body mass index (BMI) of the study population was 34.5
      (range, 22.7-59). CONCLUSION: A significant number of patients with spontaneous
      CSF rhinorrhea may have more than one skull base defect present at the time of
      presentation. The clinical significance of this finding in surgical and medical
      decision making is not clear at this time.

PMID- 25590326
TI  - American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF)
      will publish its latest "Clinical practice guideline: allergic rhinitis (AR) in
      February, 2015".

PMID- 25590328
TI  - Bis(thienothiophenyl) diketopyrrolopyrrole-based conjugated polymers with various
      branched alkyl side chains and their applications in thin-film transistors and
      polymer solar cells.
AB  - New thienothiophene-flanked diketopyrrolopyrrole and thiophene-containing pi
      extended conjugated polymers with various branched alkyl side-chains were
      successfully synthesized. 2-Octyldodecyl, 2-decyltetradecyl, 2
      tetradecylhexadecyl, 2-hexadecyloctadecyl, and 2-octadecyldocosyl groups were
      selected as the side-chain moieties and were anchored to the N-positions of the
      thienothiophene-flanked diketopyrrolopyrrole unit. All five polymers were found
      to be soluble owing to the bulkiness of the side chains. The thin-film transistor
      based on the 2-tetradecylhexadecyl-substituted polymer showed the highest hole
      mobility of 1.92 cm2 V(-1) s(-1) due to it having the smallest pi-pi stacking
      distance between the polymer chains, which was determined by grazing incidence X
      ray diffraction. Bulk heterojunction polymer solar cells incorporating [6,6]
      phenyl-C71-butyric acid methyl ester as the n-type molecule and the additive 1,8
      diiodooctane (1 vol %) were also constructed from the synthesized polymers
      without thermal annealing; the device containing the 2-octyldodecyl-substituted
      polymer exhibited the highest power conversion efficiency of 5.8%. Although all
      the polymers showed similar physical properties, their device performance was
      clearly influenced by the sizes of the branched alkyl side-chain groups.

PMID- 25590329
TI  - Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in
      insect muscle.
AB  - This paper proposes a remarkably facile staining protocol to visually investigate
      dynamic physiological events in insect tissues. We attempted to monitor Ca2+
      dynamics during contraction of electrically stimulated living muscle. Advances in
      circuit miniaturization and insect neuromuscular physiology have enabled the
      hybridization of living insects and man-made electronic components, such as
      microcomputers, the result of which has been often referred as a Living Machine,
      Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use,
      electrical stimulation parameters need to be optimized to induce desired muscle
      response (motor action) and minimize the damage in the muscle due to the
      electrical stimuli. Staining tissues and organs as well as measuring the dynamics
      of chemicals of interest in muscle should be conducted to quantitatively and
      systematically evaluate the effect of various stimulation parameters on the
      muscle response. However, existing staining processes require invasive surgery
      and/or arduous procedures using genetically encoded sensors. In this study, we
      developed a non-invasive and remarkably facile method for staining, in which
      chemical indicators can be orally administered (oral dosing). A chemical Ca2+
      indicator was orally introduced into an insect of interest via food containing
      the chemical indicator and the indicator diffused from the insect digestion
      system to the target muscle tissue. We found that there was a positive
      relationship between the fluorescence intensity of the indicator and the
      frequency of electrical stimulation which indicates the orally dosed indicator
      successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing
      method has a potential to globally stain tissues including neurons, and
      investigating various physiological events in insects. 

PMID- 25590330
TI  - The formation of multi-synaptic connections by the interaction of synaptic and
      structural plasticity and their functional consequences.
AB  - Cortical connectivity emerges from the permanent interaction between neuronal
      activity and synaptic as well as structural plasticity. An important
      experimentally observed feature of this connectivity is the distribution of the
      number of synapses from one neuron to another, which has been measured in several
      cortical layers. All of these distributions are bimodal with one peak at zero and
      a second one at a small number (3-8) of synapses. In this study, using a
      probabilistic model of structural plasticity, which depends on the synaptic
      weights, we explore how these distributions can emerge and which functional
      consequences they have. We find that bimodal distributions arise generically from
      the interaction of structural plasticity with synaptic plasticity rules that
      fulfill the following biological realistic constraints: First, the synaptic
      weights have to grow with the postsynaptic activity. Second, this growth curve
      and/or the input-output relation of the postsynaptic neuron have to change sub
      linearly (negative curvature). As most neurons show such input-output-relations,
      these constraints can be fulfilled by many biological reasonable systems. Given
      such a system, we show that the different activities, which can explain the layer
      specific distributions, correspond to experimentally observed activities.
      Considering these activities as working point of the system and varying the pre-
      or postsynaptic stimulation reveals a hysteresis in the number of synapses. As a
      consequence of this, the connectivity between two neurons can be controlled by
      activity but is also safeguarded against overly fast changes. These results
      indicate that the complex dynamics between activity and plasticity will, already
      between a pair of neurons, induce a variety of possible stable synaptic
      distributions, which could support memory mechanisms. 

PMID- 25590331
TI  - Uptake and population-level impact of expedited partner therapy (EPT) on
      Chlamydia trachomatis and Neisseria gonorrhoeae: the Washington State community
      level randomized trial of EPT.
AB  - BACKGROUND: Expedited partner therapy (EPT), the practice of treating the sex
      partners of persons with sexually transmitted infections without their medical
      evaluation, increases partner treatment and decreases gonorrhea and chlamydia
      reinfection rates. We conducted a stepped-wedge, community-level randomized trial
      to determine whether a public health intervention promoting EPT could increase
      its use and decrease chlamydia test positivity and gonorrhea incidence in women.
      METHODS AND FINDINGS: The trial randomly assigned local health jurisdictions
      (LHJs) in Washington State, US, into four study waves. Waves instituted the
      intervention in randomly assigned order at intervals of 6-8 mo. Of the state's 25
      LHJs, 24 were eligible and 23 participated. Heterosexual individuals with
      gonorrhea or chlamydial infection were eligible for the intervention. The study
      made free patient-delivered partner therapy (PDPT) available to clinicians, and
      provided public health partner services based on clinician referral. The main
      study outcomes were chlamydia test positivity among women ages 14-25 y in 219
      sentinel clinics, and incidence of reported gonorrhea in women, both measured at
      the community level. Receipt of PDPT from clinicians was evaluated among randomly
      selected patients. 23 and 22 LHJs provided data on gonorrhea and chlamydia
      outcomes, respectively. The intervention increased the percentage of persons
      receiving PDPT from clinicians (from 18% to 34%, p < 0.001) and the percentage
      receiving partner services (from 25% to 45%, p < 0.001). Chlamydia test
      positivity and gonorrhea incidence in women decreased over the study period, from
      8.2% to 6.5% and from 59.6 to 26.4 per 100,000, respectively. After adjusting for
      temporal trends, the intervention was associated with an approximately 10%
      reduction in both chlamydia positivity and gonorrhea incidence, though the
      confidence bounds on these outcomes both crossed one (chlamydia positivity
      prevalence ratio = 0.89, 95% CI 0.77-1.04, p = 0.15; gonorrhea incidence rate
      ratio = 0.91, 95% CI .71-1.16, p = 0.45). Study findings were potentially limited
      by inadequate statistical power, by the institution of some aspects of the study
      intervention outside of the research randomization sequence, and by the fact that
      LHJs did not constitute truly isolated sexual networks. CONCLUSIONS: A public
      health intervention promoting the use of free PDPT substantially increased its
      use and may have resulted in decreased chlamydial and gonococcal infections at
      the population level. TRIAL REGISTRATION: ClinicalTrials.gov NCT01665690.

PMID- 25590332
TI  - Antiarrhythmic agents and the risk of malignant neoplasm of liver and
      intrahepatic bile ducts.
AB  - BACKGROUND: The objective of this study was to determine the association between
      the use of antiarrhythmic agents and the risk of malignant neoplasm of liver and
      intrahepatic bile ducts (MNLIHD). METHODS: We used the research database of the
      Taiwan National Health Insurance Program to conduct a population-based, case
      control study. We identified 9944 patients with antiarrhythmic history who were
      first diagnosed as having MNLIHD between 2005 and 2010. We identified an
      additional 19,497 patients with antiarrhythmic history in the same period who did
      not develop MNLIHD and were frequency-matched using age, sex, and index year to
      form a control group. Five commercially available antiarrhythmic agents,
      amiodarone, mexiletine, propafenone, quinidine, and procainamide, were analyzed.
      RESULTS: The adjusted odds ratio (OR) of MNLIHD was 1.60 (95% confidence interval
      [CI], 1.45-1.77) for amiodarone users versus nonamiodarone users. In subgroup
      analysis, amiodarone use was significantly associated with an increased risk of
      MNLIHD with an adjusted OR of 18.0 (95% CI, 15.7-20.5) for patients with
      comorbidities compared to an OR of 2.43 (95% CI, 1.92-3.06) for those without
      comorbidities. After adjustment for age, sex, statins, anti-diabetes medications,
      non-steroidal antiinflammatory drugs, propafenone use, quinidine use, and
      comorbidities, the ORs were 1.49, 1.66, and 1.79 for MNLIHD associated with
      annual mean defined daily doses of <= 30, 31-145, and >145, respectively.
      CONCLUSIONS: The results of the present study indicated that amiodarone might be
      associated with the development of MNLIHD in a dose-dependent manner,
      particularly among patients with comorbidities.

PMID- 25590334
TI  - Real-time continuous glucose monitoring reduces the duration of hypoglycemia
      episodes: a randomized trial in very low birth weight neonates.
AB  - OBJECTIVES: Hypoglycemia is frequent in very low birth weight (VLBW) neonates and
      compromises their neurological outcome. The aim of this study was to compare real
      time continuous glucose monitoring system (RT-CGMS) to standard methods by
      intermittent capillary blood glucose testing in detecting and managing
      hypoglycemia. STUDY DESIGN: Forty-eight VLBW neonates were enrolled in this
      prospective study. During their 3 first days of life, their glucose level was
      monitored either by RT-CGMS (CGM-group), or by intermittent capillary glucose
      testing (IGM-group) associated with a blind-CGMS to detect retrospectively missed
      hypoglycemia. Outcomes were the number and duration of hypoglycemic (<= 50 mg/dl)
      episodes per patient detected by CGMS. RESULTS: Forty-three monitorings were
      analyzed (IGM n = 21, CGM n = 22), with a median recording time of 72 hours. In
      the IGM group, blind-CGMS revealed a significantly higher number of hypoglycemia
      episodes than capillary blood glucose testing (1.2 +/- 0.4 vs 0.4 +/- 0.2
      episode/patient, p<0.01). In the CGM-group, the use of RT-CGMS made it possible
      (i) to detect the same number of hypoglycemia episodes as blind-CGMS (1.2 +/- 0.4
      episode/patient), (ii) to adapt the glucose supply in neonates with hypoglycemia
      (increased supply during days 1 and 2), and (iii) to significantly reduce the
      duration of hypoglycemia episodes per patient (CGM 44[10-140] min versus IGM
      95[15-520] min, p<0.05). Furthermore, it reduced the number of blood samples (CGM
      16.9 +/- 1.0 vs IGM 21.9 +/- 1.0 blood sample/patient, p<0.001). CONCLUSION: RT
      CGMS played a beneficial role in managing hypoglycemia in VLBW neonates by
      adjusting the carbohydrate supply to the individual needs and by reducing the
      duration of hypoglycemia episodes. The clinical significance of the biological
      differences observed in our study need to be explored.

PMID- 25590333
TI  - Transcriptome analysis and systemic RNAi response in the African sweetpotato
      weevil (Cylas puncticollis, Coleoptera, Brentidae).
AB  - The African sweetpotato weevil (SPW) Cylas puncticollis Boheman is one of the
      most important constraints of sweetpotato production in Sub-Saharan Africa and
      yet is largely an uncharacterized insect pest. Here, we report on the
      transcriptome analysis of SPW generated using an Illumina platform. More than 213
      million sequencing reads were obtained and assembled into 89,599 contigs. This
      assembly was followed by a gene ontology annotation. Subsequently, a
      transcriptome search showed that the necessary RNAi components relevant to the
      three major RNAi pathways, were found to be expressed in SPW. To address the
      functionality of the RNAi mechanism in this species, dsRNA was injected into
      second instar larvae targeting laccase2, a gene which encodes an enzyme involved
      in the sclerotization of insect exoskeleton. The body of treated insects showed
      inhibition of sclerotization, leading eventually to death. Quantitative Real Time
      PCR (qPCR) confirmed this phenotype to be the result of gene silencing. Together,
      our results provide valuable sequence data on this important insect pest and
      demonstrate that a functional RNAi pathway with a strong and systemic effect is
      present in SPW and can further be explored as a new strategy for controlling this
      important pest. 

PMID- 25590335
TI  - Green fluorescent protein-based expression screening of membrane proteins in
      Escherichia coli.
AB  - The production of recombinant membrane proteins for structural and functional
      studies remains technically challenging due to low levels of expression and the
      inherent instability of many membrane proteins once solubilized in detergents. A
      protocol is described that combines ligation independent cloning of membrane
      proteins as GFP fusions with expression in Escherichia coli detected by GFP
      fluorescence. This enables the construction and expression screening of multiple
      membrane protein/variants to identify candidates suitable for further investment
      of time and effort. The GFP reporter is used in a primary screen of expression by
      visualizing GFP fluorescence following SDS polyacrylamide gel electrophoresis
      (SDS-PAGE). Membrane proteins that show both a high expression level with minimum
      degradation as indicated by the absence of free GFP, are selected for a secondary
      screen. These constructs are scaled and a total membrane fraction prepared and
      solubilized in four different detergents. Following ultracentrifugation to remove
      detergent-insoluble material, lysates are analyzed by fluorescence detection size
      exclusion chromatography (FSEC). Monitoring the size exclusion profile by GFP
      fluorescence provides information about the mono-dispersity and integrity of the
      membrane proteins in different detergents. Protein: detergent combinations that
      elute with a symmetrical peak with little or no free GFP and minimum aggregation
      are candidates for subsequent purification. Using the above methodology, the
      heterologous expression in E. coli of SED (shape, elongation, division, and
      sporulation) proteins from 47 different species of bacteria was analyzed. These
      proteins typically have ten transmembrane domains and are essential for cell
      division. The results show that the production of the SEDs orthologues in E. coli
      was highly variable with respect to the expression levels and integrity of the
      GFP fusion proteins. The experiment identified a subset for further
      investigation. 

PMID- 25590336
TI  - Log in and breathe out: internet-based recovery training for sleepless employees
      with work-related strain - results of a randomized controlled trial.
AB  - OBJECTIVES: The primary purpose of this randomized controlled trial (RCT) was to
      evaluate the efficacy of a guided internet-based recovery training for employees
      who suffer from both work-related strain and sleep problems (GET.ON Recovery).
      The recovery training consisted of six lessons, employing well-established
      methods from cognitive behavioral therapy for insomnia (CBT-I) such as sleep
      restriction, stimulus control, and hygiene interventions as well as techniques
      targeted at reducing rumination and promoting recreational activities. METHODS:
      In a two-arm RCT (N=128), the effects of GET.ON Recovery were compared to a
      waitlist-control condition (WLC) on the basis of intention-to-treat analyses.
      German teachers with clinical insomnia complaints (Insomnia Severity Index >=15)
      and work-related rumination (Irritation Scale, cognitive irritation subscale
      >=15) were included. The primary outcome measure was insomnia severity. RESULTS:
      Analyses of covariance (ANCOVA) revealed that, compared to the WLC, insomnia
      severity of the intervention group decreased significantly stronger (F=74.11,
      P<0.001) with a d=1.45 [95% confidence interval (95% CI) 1.06-1.84] The number
      needed to treat (NNT) was <2 for reliable change and NNT <4 for reduction in
      expert-rated diagnosis of primary insomnia. CONCLUSION: The training
      significantly reduces sleep problems and fosters mental detachment from work and
      recreational behavior among adult stressed employees at post-test and 6-months
      follow up. Given the low threshold access this training could reach out to a
      large group of stressed employees when results are replicated in other studies.

PMID- 25590337
TI  - Effect of antenatal parasitic infections on anti-vaccine IgG levels in children:
      a prospective birth cohort study in Kenya.
AB  - BACKGROUND: Parasitic infections are prevalent among pregnant women in sub
      Saharan Africa. We investigated whether prenatal exposure to malaria and/or
      helminths affects the pattern of infant immune responses to standard vaccinations
      against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and
      tetanus toxoid (TT). METHODS AND FINDINGS: 450 Kenyan women were tested for
      malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths
      during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their
      newborns were followed biannually to age 36 months and tested for absolute levels
      of IgG against Hib, DT, Hep B, and TT at each time point. Newborns' cord blood
      (CB) lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma
      haematobium worm antigen (SWAP), and filaria antigen (BMA) were also assessed.
      Three immunophenotype categories were compared: i) tolerant (those having
      Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective
      Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA); ii)
      sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB
      recall response to respective parasite antigen); or iii) unexposed (no evidence
      of maternal infection or CB recall response). Overall, 78.9% of mothers were
      infected with LF (44.7%), schistosomiasis (32.4%), malaria (27.6%) or hookworm
      (33.8%). Antenatal maternal malaria, LF, and hookworm were independently
      associated with significantly lower Hib-specific IgG. Presence of multiple
      maternal infections was associated with lower infant IgG levels against Hib and
      DT antigens post-vaccination. Post-vaccination IgG levels were also significantly
      associated with immunophenotype: malaria-tolerized infants had reduced response
      to DT, whereas filaria-tolerized infants showed reduced response to Hib.
      CONCLUSIONS: There is an impaired ability to develop IgG antibody responses to
      key protective antigens of Hib and diphtheria in infants of mothers infected with
      malaria and/or helminths during pregnancy. These findings highlight the
      importance of control and prevention of parasitic infections among pregnant
      women.

PMID- 25590340
TI  - The myth of the angry atheist.
AB  - Atheists are often portrayed in the media and elsewhere as angry individuals.
      Although atheists disagree with the pillar of many religions, namely the
      existence of a God, it may not necessarily be the case that they are angry
      individuals. The prevalence and accuracy of angry-atheist perceptions were
      examined in 7 studies with 1,677 participants from multiple institutions and
      locations in the United States. Studies 1-3 revealed that people believe atheists
      are angrier than believers, people in general, and other minority groups, both
      explicitly and implicitly. Studies 4-7 then examined the accuracy of these
      beliefs. Belief in God, state anger, and trait anger were assessed in multiple
      ways and contexts. None of these studies supported the idea that atheists are
      particularly angry individuals. Rather, these results support the idea that
      people believe atheists are angry individuals, but they do not appear to be
      angrier than other individuals in reality.

PMID- 25590341
TI  - Potential job facilitation benefits of "water cooler" conversations: the
      importance of social interactions in the workplace.
AB  - This study looked at the extent to which personality and cultural factors
      predicted participants' perceptions of the importance private interactions played
      in the workplace. The 134 participants read a vignette (where a new employee
      socially interacted at low or high levels with co-workers) and completed the Big
      Five Inventory, Social Axioms Survey, and questions concerning expected workplace
      experiences. Results indicated employees who engaged in high levels of private
      interaction with co-workers were expected to be better liked, to receive better
      performance evaluations, were more likely to receive co-worker assistance, and
      were thought to be more likely chosen for future projects. However, the
      personality and social axiom variables studied did not significantly interact
      with social interaction to influence expectations of workplace outcomes.

PMID- 25590338
TI  - Receptor tyrosine kinase ERBB4 mediates acquired resistance to ERBB2 inhibitors
      in breast cancer cells.
AB  - Approximately 25% of breast cancers overexpress and depend on the receptor
      tyrosine kinase ERBB2, one of 4 ERBB family members. Targeted therapies directed
      against ERBB2 have been developed and used clinically, but many patients continue
      to develop resistance to such therapies. Although much effort has been focused on
      elucidating the mechanisms of acquired resistance to ERBB2-targeted therapies,
      the involvement of ERBB4 remains elusive and controversial. We demonstrate that
      genetic ablation of ERBB4, but not ERBB1-3, led to apoptosis in lapatinib
      resistant cells, suggesting that the efficacy of pan-ERBB inhibitors was, at
      least in part, mediated by the inhibition of ERBB4. Moreover, ERBB4 was
      upregulated at the protein level in ERBB2+ breast cancer cell lines selected for
      acquired lapatinib resistance in vitro and in MMTV-Neu mice following prolonged
      lapatinib treatment. Knockdown of ERBB4 caused a decrease in AKT phosphorylation
      in resistant cells but not in sensitive cells, suggesting that ERBB4 activated
      the PI3K/AKT pathway in lapatinib-resistant cells. Importantly, ERBB4 knockdown
      triggered apoptosis not only in lapatinib-resistant cells but also in trastuzumab
      resistant cells. Our results suggest that although ERBB4 is dispensable for naive
      ERBB2+ breast cancer cells, it may play a key role in the survival of ERBB2+
      cancer cells after they develop resistance to ERBB2 inhibitors, lapatinib and
      trastuzumab. 

PMID- 25590342
TI  - Engaged, committed and helpful employees: the role of psychological empowerment.
AB  - Although previous research has been focused on the relationship among
      personality, empowerment, and outcomes, little is known about the incremental
      effect of empowerment on positive work outcomes. This article aims at exploring
      the relation between personality factors (i.e., extraversion and
      conscientiousness) and positive work outcomes (i.e., work engagement, affective
      organizational commitment, and organizational citizenship behavior), and at
      determining the incremental effect of psychological empowerment on these
      outcomes. A convenience sample from three organizations has been used for data
      collection (N = 258; 52% women, mean age 38.55 years, SD = 10.21). Hierarchical
      multiple regressions indicate that personality and psychological empowerment
      explain a significant amount of the variance in the positive organizational
      outcomes, and that psychological empowerment has a significant incremental value
      over demographics and personality for the studied outcomes.

PMID- 25590343
TI  - Professional self-efficacy as a predictor of burnout and engagement: the role of
      challenge and hindrance demands.
AB  - The objective of the current study is to analyze the role of professional self
      efficacy as a predictor of psychosocial well-being (i.e., burnout and engagement)
      following the Social Cognitive Theory of Albert Bandura (1997). Structural
      Equation Modeling was performed in a sample of secondary school teachers (n =
      460) and users of Information and Communication Technology (n = 596). Results
      show empirical support for the predicting role that professional self-efficacy
      plays in the perception of challenge (i.e., mental overload) and hindrance
      demands (i.e., role conflict, lack of control, and lack of social support), which
      are in turn related to burnout (i.e., erosion process) and engagement (i.e.,
      motivational process). Specifically, employees with more professional self
      efficacy will perceive more challenge demands and fewer hindrance demands, and
      this will in turn relate to more engagement and less burnout. A multi-group
      analysis showed that the research model was invariant across both samples.
      Theoretical and practical implications are discussed.

PMID- 25590344
TI  - Assessment of anger terms in Hebrew: a gender comparison.
AB  - ABSTRACT Appraisal of anger terms is based on past experience recollections,
      social norms, and gender roles. The objectives of this study were to find
      combinations of emotional components presented by a new composite variable that
      will exhibit differences between genders and differentiate between anger terms in
      Hebrew. The sample was comprised of forty students, Hebrew native speakers who
      participated in a web based study. Participants were asked to rate eight anger
      terms in Hebrew on a number of features that comprised five emotional components:
      subjective feelings states body reactions, expressions, action tendencies, and
      cognitive evaluations. A two-factor between-subjects multivariate analysis of
      variance (MANOVA) was conducted. A simplified multivariate composite, defined as
      subjective experience minus regulation, explained 10% of the gender difference.
      Another simplified composite, which combines the additive effect of the
      subjective experience and the actions that accompany this emotional state,
      explained 14% of difference between the anger terms. The findings are discussed
      with respect to appraisal theory and social constructivist conceptualization. 

PMID- 25590339
TI  - RNA-guided isomerization of uridine to pseudouridine--pseudouridylation.
AB  - Box H/ACA ribonucleoproteins (RNPs), each consisting of one unique guide RNA and
      4 common core proteins, constitute a family of complex enzymes that catalyze, in
      an RNA-guided manner, the isomerization of uridines to pseudouridines (Psis) in
      RNAs, a reaction known as pseudouridylation. Over the years, box H/ACA RNPs have
      been extensively studied revealing many important aspects of these RNA modifying
      machines. In this review, we focus on the composition, structure, and biogenesis
      of H/ACA RNPs. We explain the mechanism of how this enzyme family recognizes and
      specifies its target uridine in a substrate RNA. We discuss the substrates of box
      H/ACA RNPs, focusing on rRNA (rRNA) and spliceosomal small nuclear RNA (snRNA).
      We describe the modification product Psi and its contribution to RNA function.
      Finally, we consider possible mechanisms of the bone marrow failure syndrome
      dyskeratosis congenita and of prostate and other cancers linked to mutations in
      H/ACA RNPs. 

PMID- 25590346
TI  - Developmental pathways to attention-deficit/hyperactivity disorder and disruptive
      behavior disorders: Investigating the impact of the stress response on executive
      functioning.
AB  - A current theory suggests multiple pathways to the onset of attention
      deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder
      or conduct disorder, proposing that heterogeneous factors lead to various
      patterns of behavior, cognitive impairments, and even physiological signs which
      are categorized as ADHD and comorbid disorders. This review focused on one
      proposed pathway to the onset of ADHD and ODD/CD in order to examine how low
      physiological arousal, as indicated by atypical hypothalamic-pituitary-adrenal
      axis and sympathetic adrenomedullary functioning, might be associated with
      cognitive impairment. First, the cognitive deficits associated with ADHD and
      disruptive behavior disorders were reviewed. In order to understand the atypical
      response, studies of the typical stress response and its relationship to
      cognition, particularly executive functioning, were then examined. Finally, this
      review summarized findings of an atypical stress response among children with
      ADHD and ODD/CD. Review of the literature led to the conclusion that the
      theorized pathway may be improved by taking into account the effects of stress on
      executive functioning given that an atypical stress response would likely be
      associated with impairment in this area. Future research directions needed to
      advance our understanding of the relationship between low arousal, ADHD, and
      ODD/CD were highlighted. 

PMID- 25590345
TI  - The use of the puzzle box as a means of assessing the efficacy of environmental
      enrichment.
AB  - Environmental enrichment can dramatically influence the development and function
      of neural circuits. Further, enrichment has been shown to successfully delay the
      onset of symptoms in models of Huntington's disease (1-4), suggesting
      environmental factors can evoke a neuroprotective effect against the progressive,
      cellular level damage observed in neurodegenerative disorders. The ways in which
      an animal can be environmentally enriched, however, can vary considerably.
      Further, there is no straightforward manner in which the effects of environmental
      enrichment can be assessed: most methods require either fairly complicated
      behavioral paradigms and/or postmortem anatomical/physiological analyses. This
      protocol describes the use of a simple and inexpensive behavioral assay, the
      Puzzle Box (5-7) as a robust means of determining the efficacy of increased
      social, sensory and motor stimulation on mice compared to cohorts raised in
      standard laboratory conditions. This simple problem solving task takes advantage
      of a rodent's innate desire to avoid open enclosures by seeking shelter.
      Cognitive ability is assessed by adding increasingly complex impediments to the
      shelter's entrance. The time a given subject takes to successfully remove the
      obstructions and enter the shelter serves as the primary metric for task
      performance. This method could provide a reliable means of rapidly assessing the
      efficacy of different enrichment protocols on cognitive function, thus paving the
      way for systematically determining the role specific environmental factors play
      in delaying the onset of neurodevelopmental and neurodegenerative disease. 

PMID- 25590347
TI  - Quantitative residue-specific protein backbone torsion angle dynamics from
      concerted measurement of 3J couplings.
AB  - Three-bond (3)J(C'C') and (3)J(HNHalpha) couplings in peptides and proteins are
      functions of the intervening backbone torsion angle phi. In well-ordered regions,
      (3)J(HNHalpha) is tightly correlated with (3)J(C'C'), but the presence of large
      phi angle fluctuations differentially affects the two types of couplings.
      Assuming the phi angles follow a Gaussian distribution, the width of this
      distribution can be extracted from (3)J(C'C') and (3)J(HNHalpha), as demonstrated
      for the folded proteins ubiquitin and GB3. In intrinsically disordered proteins,
      slow transverse relaxation permits measurement of (3)J(C'C') and (3)J(HNH)
      couplings at very high precision, and impact of factors other than the
      intervening torsion angle on (3)J will be minimal, making these couplings
      exceptionally valuable structural reporters. Analysis of alpha-synuclein yields
      rather homogeneous widths of 69 +/- 6 degrees  for the phi angle distributions
      and (3)J(C'C') values that agree well with those of a recent maximum entropy
      analysis of chemical shifts, J couplings, and (1)H-(1)H NOEs. Data are consistent
      with a modest (<=30%) population of the polyproline II region.

PMID- 25590349
TI  - T538 phosphorylation, Pin-ing p63-Itch stability.

PMID- 25590348
TI  - Centrosomal nucleolin is required for microtubule network organization.
AB  - Nucleolin is a pleiotropic protein involved in a variety of cellular processes.
      Although multipolar spindle formation has been observed after nucleolin
      depletion, the roles of nucleolin in centrosome regulation and functions have not
      been addressed. Here we report using immunofluorescence and biochemically
      purified centrosomes that nucleolin co-localized only with one of the centrioles
      during interphase which was further identified as the mature centriole. Upon
      nucleolin depletion, cells exhibited an amplification of immature centriole
      markers surrounded by irregular pericentrin staining; these structures were
      exempt from maturation markers and unable to nucleate microtubules. Furthermore,
      the microtubule network was disorganized in these cells, exhibiting frequent non
      centrosomal microtubules. At the mature centriole a reduced kinetics in the
      centrosomal microtubule nucleation phase was observed in live silenced cells, as
      well as a perturbation of microtubule anchoring. Immunoprecipitation experiments
      showed that nucleolin belongs to protein complexes containing 2 key centrosomal
      proteins, gamma-tubulin and ninein, involved in microtubule nucleation and
      anchoring steps. Altogether, our study uncovered a new role for nucleolin in
      restricting microtubule nucleation and anchoring at centrosomes in interphase
      cells. 

PMID- 25590351
TI  - Cancer research in Brazil - stuck in second gear?
AB  - This article describes the main issues regarding clinical cancer research in
      Brazil, including both the opportunities and the hurdles. Scientists and
      clinicians in this field had the opportunity to talk to regulatory agencies and
      to the Health Ministry representative at a meeting held in the State of Rio de
      Janeiro, Brazil, in April 2014. Our conclusions are that we do indeed have
      opportunities; however, we need to move forward regarding partnerships between
      academia and industry, increase the availability of funding, and provide easier
      navigation through the regulatory processes. 

PMID- 25590350
TI  - Bilateral repetitive transcranial magnetic stimulation for treatment-resistant
      depression: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - There has been concern regarding the use of controversial paradigms for
      repetitive transcranial magnetic stimulation (rTMS) to manage treatment-resistant
      depression (TRD). This meta-analysis assessed the efficacy of bilateral rTMS
      compared with unilateral and sham rTMS in patients with TRD. PubMed, Embase,
      CENTRAL, PsycINFO, Web of Science, EAGLE and NTIS databases were searched to
      identify relevant studies, and randomized controlled trials (RCTs) on bilateral
      rTMS for TRD patients were included. The response was defined as the primary
      outcome, and remission was the secondary outcome. Ten RCTs that included 634
      patients met the eligibility criteria. The risk ratio (RRs) of both the primary
      and secondary outcomes of bilateral rTMS showed non-significant increases
      compared to unilateral rTMS (RR=1.01, P=0.93; odds ratio [OR]=0.77, P=0.22).
      Notably, the RR of the primary bilateral rTMS outcome was significantly increased
      compared to that for sham rTMS (RR=3.43, P=0.0004). The results of our analysis
      demonstrated that bilateral rTMS was significantly more effective than sham rTMS
      but not unilateral rTMS in patients with TRD. Thus, bilateral rTMS may not be a
      useful paradigm for patients with TRD.

PMID- 25590354
TI  - Fluence inhomogeneities due to a ripple filter induced Moire effect.
AB  - At particle therapy facilities with pencil beam scanning, the implementation of a
      ripple filter (RiFi) broadens the Bragg peak, so fewer energy steps from the
      accelerator are required for a homogeneous dose coverage of the planning target
      volume (PTV). However, sharply focusing the scanned pencil beams at the RiFi
      plane by ion optical settings can lead to a Moire effect, causing fluence
      inhomogeneities at the isocenter. This has been experimentally proven at the
      Heidelberg Ionenstrahl-Therapiezentrum (HIT), Universitatsklinikum Heidelberg,
      Germany. 150 MeV u(-1) carbon-12 ions are used for irradiation with a 3 mm thick
      RiFi. The beam is focused in front of and as close to the RiFi plane as possible.
      The pencil beam width is estimated to be 0.78 mm at a 93 mm distance from the
      RiFi. Radiographic films are used to obtain the fluence profile 30 mm in front of
      the isocenter, 930 mm from the RiFi. The Monte Carlo (MC) code SHIELD-HIT12A is
      used to determine the RiFi-induced inhomogeneities in the fluence distribution at
      the isocenter for a similar setup, pencil beam widths at the RiFi plane ranging
      from sigmachi(RiFi to 1.2 mm and for scanning step sizes ranging from 1.5 to 3.7
      mm. The beam application and monitoring system (BAMS) used at HIT is modelled and
      simulated. When the width of the pencil beams at the RiFi plane is much smaller
      than the scanning step size, the resulting inhomogeneous fluence distribution at
      the RiFi plane interfers with the inhomogeneous RiFi mass distribution and
      fluence inhomogeneity can be observed at the isocenter as large as an 8%
      deviation from the mean fluence. The inverse of the fluence ripple period at the
      isocenter is found to be the difference between the inverse of the RiFi period
      and the inverse of the scanning step size. We have been able to use MC
      simulations to reproduce the spacing of the ripple stripes seen in films
      irradiated at HIT. Our findings clearly indicate that pencil beams sharply
      focused near the RiFi plane result in fluence inhomogeneity at the isocenter. In
      the normal clinical application, such a setting should generally be avoided.

PMID- 25590352
TI  - Epilepsy-induced electrocardiographic alterations following cardiac ischemia and
      reperfusion in rats.
AB  - The present study evaluated electrocardiographic alterations in rats with
      epilepsy submitted to an acute myocardial infarction (AMI) model induced by
      cardiac ischemia and reperfusion. Rats were randomly divided into two groups:
      control (n=12) and epilepsy (n=14). It was found that rats with epilepsy
      presented a significant reduction in atrioventricular block incidence following
      the ischemia and reperfusion procedure. In addition, significant alterations were
      observed in electrocardiogram intervals during the stabilization, ischemia, and
      reperfusion periods of rats with epilepsy compared to control rats. It was noted
      that rats with epilepsy presented a significant increase in the QRS interval
      during the stabilization period in relation to control rats (P<0.01). During the
      ischemia period, there was an increase in the QRS interval (P<0.05) and a
      reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy
      compared to control rats. During the reperfusion period, a significant reduction
      in the QT interval (P<0.01) was verified in the epilepsy group in relation to the
      control group. Our results indicate that rats submitted to an epilepsy model
      induced by pilocarpine presented electrical conductivity alterations of cardiac
      tissue, mainly during an AMI episode. 

PMID- 25590353
TI  - PPARgamma induces growth inhibition and apoptosis through upregulation of insulin
      like growth factor-binding protein-3 in gastric cancer cells.
AB  - Peroxisome proliferator activator receptor-gamma (PPARgamma) is a ligand
      activated transcriptional factor involved in the carcinogenesis of various
      cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor
      suppressor gene that has anti-apoptotic activity. The purpose of this study was
      to investigate the anticancer mechanism of PPARgamma with respect to IGFBP-3.
      PPARgamma was overexpressed in SNU-668 gastric cancer cells using an adenovirus
      gene transfer system. The cells in which PPARgamma was overexpressed exhibited
      growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3
      expression. We investigated the underlying molecular mechanisms of PPARgamma in
      SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase
      activity was increased up to 15-fold in PPARgamma transfected cells, suggesting
      that PPARgamma may directly interact with IGFBP-3 promoter to induce its
      expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase
      activity was markedly reduced in cells without putative p53-binding sites (
      Delta1755, -Delta1795). This suggests that the critical PPARgamma-response region
      is located within the p53-binding region of the IGFBP-3 promoter. We further
      demonstrated an increase in PPARgamma-induced luciferase activity even in cells
      treated with siRNA to silence p53 expression. Taken together, these data suggest
      that PPARgamma exhibits its anticancer effect by increasing IGFBP-3 expression,
      and that IGFBP-3 is a significant tumor suppressor.

PMID- 25590356
TI  - Effects of H 2SO4 and O 2 on Hg0 uptake capacity and reversibility of sulfur
      impregnated activated carbon under dynamic conditions.
AB  - Powder activated carbon (AC) injection is widely considered as the most viable
      technology for removing gaseous elemental mercury (Hg(0)) in flue gases of coal
      fired power plants. However, sulfuric acid (H2SO4) can form on the external and
      internal surfaces of AC particles due to the presence of sulfur oxides, nitrogen
      oxides, oxygen, and moisture in flue gases. This work focuses on the effects of
      H2SO4 and O2 on the Hg(0) uptake capacity and reversibility of sulfur impregnated
      activated carbon (SIAC) under dynamic conditions. Experiments were conducted with
      25 MUg-Hg(0)/m(3) of nitrogen or air, using a semicontinuous flow fixed-bed
      reactor kept at 120 or 180  degrees C. H2SO4 had a profound hindering effect on
      Hg(0) uptake due to pore blockage. O2 significantly enhanced Hg(0) uptake and its
      reversibility, via the oxidation of Hg(0) which facilitated chemisorption and the
      subsequent physisorption onto chemically adsorbed Hg. Absorption of Hg in H2SO4
      was unlikely a significant contributor, when Hg(0) concentrations were at levels
      of typical power plants (tens of ppb). The reversibility of and relative
      contributions of physisorption and chemisorption to Hg(0) uptake would change
      with Hg(0) concentrations in flue gases. These findings could be significant in
      developing a complete solution for Hg capture where the handling of spent sorbent
      materials and the possible secondary pollution need to be considered.

PMID- 25590358
TI  - A Medical Food Formulation of Griffonia simplicifolia/Magnesium for Childhood
      Periodic Syndrome Therapy: An Open-Label Study on Motion Sickness.
AB  - Motion sickness (MS) is a disabling condition dominated by disagreement between
      visually perceived movement and the vestibular system's sense of movement, with
      symptoms like dizziness, fatigue, and nausea, and other autonomic disabling
      symptoms. Preparations of Griffonia simplicifolia, containing high concentrations
      of 5-HTP, might be effective for serotonin-related disorders, including MS.
      Therefore, the aim of the present study is to assess the efficacy and safety of
      the G. simplicifolia/magnesium complex in a pediatric population with MS. The
      Griffonia/magnesium complex (50 and 200 mg, respectively) was orally administered
      as a prophylactic therapy for MS twice a day for 3 months to group A, and no
      therapy for MS was administered to group B. The MS clinical signs were recorded
      by parents or, where possible, directly from children by a specific module, which
      included validated questions for the diagnoses that were administered to all
      subjects and parents of both groups. Two study groups were matched for age
      (P=.224), sex (P=.801), and z-score body-mass index (P=.173). At T0, all
      recruited subjects in both groups complained about MS. After 3 months (T1), group
      A showed an MS prevalence of 36%, significantly lower than MS prevalence in group
      B (73%) (P<.001). The findings of the present study suggest the role of the
      Griffonia/magnesium complex as a potential treatment with middle-term efficacy
      even for MS. 

PMID- 25590359
TI  - Epigenetic changes and functional study of HOXA11 in human gastric cancer.
AB  - AIM: To examine epigenetic changes and the function of HOXA11 in human gastric
      cancer (GC). MATERIALS & METHODS: Seven GC cell lines, five cases of normal
      gastric mucosa and 112 cases primary GC samples were used in this study. RESULTS:
      Expression of HOXA11 and lack of promoter region methylation were found in NCI
      N87, MKN45, BGC823 and HGC27 cells. Loss of expression and complete methylation
      were found in AGS gastric cancer cells. Reduced expression and partial
      methylation were found in MGC803 and SGC7901 cells. Restoration of HOXA11
      expression was induced by 5-aza-2'-deoxycytidine. HOXA11 was methylated in 81.25%
      (91/112) of primary GCs. The presence of methylation was associated with male
      gender, tumor size, tumor differentiation and lymph node metastasis (all p <
      0.05). Restoration of HOXA11 expression reduced cell proliferation, invasion,
      migration and induced apoptosis and G2/M phase arrest. HOXA11 was found to
      inhibit Wnt signaling by upregulating NKD1 expression. CONCLUSION: Epigenetic
      silencing of HOXA11 promotes GC proliferation, migration and invasion through
      activation of Wnt signaling.

PMID- 25590357
TI  - Perfluoroalkylfullerenes.

PMID- 25590361
TI  - Pathway toward large two-dimensional hexagonally patterned colloidal nanosheets
      in solution.
AB  - We report the solution self-assembly of an ABC block terpolymer consisting of a
      polystyrene-block-poly(ethylene oxide) (PS-b-PEO) diblock copolymer tail tethered
      to a fluorinated polyhedral oligomeric silsesquioxane (FPOSS) cage in 1,4
      dioxane/water. With increasing water content, abundant unconventional
      morphologies, including circular cylinders, two-dimensional hexagonally patterned
      colloidal nanosheets, and laterally patterned vesicles, are sequentially
      observed. The formation of toroids is dominated by two competing free energies:
      the end-cap energy of cylinders and the bending energy to form the circular
      structures. Incorporating the superhydrophobic FPOSS cages enhances the end-cap
      energy and promotes toroid formation. Lateral aggregation and fusion of the
      cylinders results in primitive nanosheets that are stabilized by the thicker rims
      to partially release the rim-cap energy. Rearrangement of the parallel-aligned
      FPOSS cylindrical cores generates hexagonally patterned nanosheets. Further
      increasing the water content induces the formation of vesicles with nanopatterned
      walls. 

PMID- 25590360
TI  - Stemistry: the control of stem cells in situ using chemistry.
AB  - A new paradigm for drug research has emerged, namely the deliberate search for
      molecules able to selectively affect the proliferation, differentiation, and
      migration of adult stem cells within the tissues in which they exist. Recently,
      there has been significant interest in medicinal chemistry toward the discovery
      and design of low molecular weight molecules that affect stem cells and thus have
      novel therapeutic activity. We believe that a successful agent from such a
      discover program would have profound effects on the treatment of many long-term
      degenerative disorders. Among these conditions are examples such as
      cardiovascular decay, neurological disorders including Alzheimer's disease, and
      macular degeneration, all of which have significant unmet medical needs. This
      perspective will review evidence from the literature that indicates that
      discovery of such agents is achievable and represents a worthwhile pursuit for
      the skills of the medicinal chemist. 

PMID- 25590362
TI  - Association of decreased rate of influenza vaccination with increased subjective
      olfactory dysfunction.
AB  - IMPORTANCE: Seasonal influenza causes significant morbidity and mortality, with
      cardiovascular and respiratory complications the most common among susceptible
      individuals. Upper respiratory tract infections (URIs) are known to precede
      olfactory dysfunction in some patients. To our knowledge, there has been no study
      assessing the possible relationship between influenza vaccination status and
      olfactory dysfunction. OBJECTIVE: To compare vaccination status of a group of
      patients with subjective olfactory dysfunction with that of a group of controls.
      DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review and
      telephone survey in a matched case-control study. Forty-two patients were
      identified via diagnosis codes who presented to a tertiary care academic
      rhinologic center with subjective smell dysfunction over the course of 1 year.
      Only post-URI and idiopathic etiologies were included. Forty-two age-, sex-, and
      race/ethnicity-matched control patients were also selected. MAIN OUTCOMES AND
      MEASURES: Demographic data, influenza vaccination status, and smoking status were
      reviewed. chi2 Testing was used. RESULTS: We were able to obtain vaccination data
      for 36 of 42 patients in the olfactory dysfunction group and 38 of 42 in the
      control group. Seven of the 36 (19%) in the olfactory dysfunction group had
      received the vaccine in the year prior to presentation compared with 16 of 38
      (42%) in the control group (P = .04). CONCLUSIONS AND RELEVANCE: Influenza
      vaccination seems to be associated with a decreased rate of subjective olfactory
      dysfunction. This is a preliminary finding, and further studies would be needed
      to elucidate the exact role of influenza and influenza vaccination in patients
      with olfactory loss.

PMID- 25590363
TI  - Hemodynamic Monitoring During Heated Intraoperative Intraperitoneal Chemotherapy
      Using the FloTrac/Vigileo System.
AB  - Cytoreductive surgery with HIPEC has provided a chance for long-term survival in
      selected patients. However, perioperative management remains a challenge for the
      anesthesiology team. The aim of this study was to evaluate the changes in
      hemodynamic parameters during hyperthermic intraperitoneal chemotherapy (HIPEC)
      using the FloTrac/Vigileo system. Forty-one consecutive patients undergoing
      cytoreductive surgery and HIPEC were enrolled. Heart rate (HR), esophageal
      temperature, and cardiac output (CO) steadily increased until the end of HIPEC.
      In the first half of HIPEC, systolic blood pressure (SBP) and central venous
      pressure (CVP) increased whereas systemic vascular resistance (SVR) decreased;
      SVR stabilized in the second half. Diastolic blood pressure (DBP), mean arterial
      pressure (MAP), and stroke volume (SV) showed no significant variation. Male
      gender was related to increased CVP, CO, and SV, and decreased SVR; age >55 years
      was related to increased SBP, and peritoneal cancer index (PCI) was correlated
      with HR, DBP, and SV. PCI >14 was associated with increased HR and decreased DBP
      and MAP. American Society of Anesthesiologists score >1 was related to decreased
      CO and SV. Patients undergoing HIPEC develop a hyperdynamic circulatory state
      because of the increased temperature, characterized by a steady decrease in SVR
      and continuous increase in HR and CO. FloTrac/Vigileo system may provide an easy
      to-handle, noninvasive monitoring tool. 

PMID- 25590364
TI  - Eriocitrin and Apigenin as New Carbonic Anhydrase VA Inhibitors from a Virtual
      Screening of Calabrian Natural Products.
AB  - In this work, we performed a structure-based virtual screening against five
      carbonic anhydrase isoforms using, as a ligand library, natural components of
      Citrus bergamia (Bergamot) and Allium cepa var. Tropea (red onion) sources, which
      are some typical Calabrian products. The most relevant Bergamot and red onion
      components, identified as potentially new hits by means of the computational
      work, were submitted to in vitro tests in order to confirm the ability to exert
      the predicted biological activity. Apigenin and eriocitrin were identified as new
      potent inhibitors of human carbonic anhydrase VA isozyme. 

PMID- 25590365
TI  - Identification of angiotensin-converting enzyme inhibitory proteins from mycelium
      of Pleurotus pulmonarius (oyster mushroom).
AB  - Pleurotus pulmonarius (grey oyster mushroom) has been acknowledged as a
      recuperative agent for many diseases in addition to its recognition as a
      nutritious provision. We performed a study on P. pulmonarius mycelium for an
      antihypertensive effect via the angiotensin-converting enzyme inhibitory
      activity. The preliminary assay on the mycelial water extract demonstrated that
      the angiotensin-converting enzyme inhibitory activity had an IC50 value of 720
      ug/mL. Further protein purifications via ammonium sulphate precipitation and RP
      HPLC resulted in 60* stronger angiotensin-converting enzyme inhibitory activity
      than that of the mycelial water extract (IC50 = 12 ug/mL). Protein identification
      and characterisation by MALDI-TOF/TOF, later corroborated by LC-MS/MS, indicated
      three proteins that are responsible for the blood pressure lowering effects via
      different mechanisms: serine proteinase inhibitor-like protein, nitrite reductase
      like protein, and DEAD/DEAH box RNA helicase-like protein. 

PMID- 25590366
TI  - Polysaccharides of Dendrobium officinale induce aquaporin 5 translocation by
      activating M3 muscarinic receptors.
AB  - Dendrobium officinale is an herbal medicine that has been clinically used to
      promote body fluid production. Previous works demonstrated that D. officinale
      polysaccharides could ameliorate symptoms of salivary secretion of patients with
      Sjogren's syndrome and in a respective mice model. In the present study, we
      investigated the underlying mechanism by which D. officinale polysaccharides
      activate M3 muscarinic receptors and induce extracellular calcium influx, leading
      to the translocation of aquaporin 5, a water channel protein, to the apical
      membrane of human submandibular gland epithelial cells. Enzymatic treatment of D.
      officinale polysaccharides suggested that they are hydrolyzed but do not permeate
      cell membranes. This finding supports the pharmacological activity of D.
      officinale polysaccharides to promote salivary secretion. 

PMID- 25590367
TI  - Essential oil of Syzygium aromaticum reverses the deficits of stress-induced
      behaviors and hippocampal p-ERK/p-CREB/brain-derived neurotrophic factor
      expression.
AB  - Syzygium aromaticum has been widely used in traditional medicine. Our study
      investigated the safety and antidepressant-like effects of the essential oil of
      S. aromaticum after acute or long-term treatment. Using GC-MS, a total of eight
      volatile constituents were identified in the essential oil of S. aromaticum. The
      single LD50 was approximately 4500 mg/kg based on a 24-h acute oral toxicity
      study. In a long-term repeated toxicity study of this essential oil (100, 200,
      and 400 mg/kg, p. o.), only 400 mg/kg induced a significant decrease in body
      weight. In addition, no significant changes in relative organ weights and
      histopathological analysis were observed in all doses of essential oil-treated
      mice compared with the control group. Furthermore, acute S. aromaticum essential
      oil administration by gavage exerted antidepressant-like effects in the forced
      swimming test (200 mg/kg, p < 0.05) and tail suspension test (100 and 200 mg/kg,
      p < 0.05). Long-term S. aromaticum essential oil treatment via gavage
      significantly increased sucrose preference (50 mg/kg, p < 0.05; 100 and 200
      mg/kg, p < 0.01) as well as elevated the protein levels of hippocampal p-ERK, p
      CREB, and brain-derived neurotrophic factor in mice exposed to chronic
      unpredictable mild stress. These results confirmed the safety of the essential
      oil of S. aromaticum and suggested that its potent antidepressant-like property
      might be attributed to the improvement in the hippocampal pERK1/2-pCREB-BDNF
      pathway in rats exposed to chronic unpredictable mild stress. 

PMID- 25590368
TI  - Aceroside VIII is a new natural selective HDAC6 inhibitor that synergistically
      enhances the anticancer activity of HDAC inhibitor in HT29 cells.
AB  - The identification of new isoform-specific histone deacetylase inhibitors is
      important for revealing the biological functions of individual histone
      deacetylase and for determining their potential use as therapeutic agents. Among
      the 11 zinc-dependent histone deacetylases that have been identified in humans,
      histone deacetylase 6 is a structurally and functionally unique enzyme. Here, we
      tested the inhibitory activity of diarylheptanoids isolated from Betula
      platyphylla against histone deacetylase 6. Aceroside VIII selectively inhibited
      histone deacetylase 6 catalytic activity and the combined treatment of aceroside
      VIII or (-)-centrolobol with A452, another selective histone deacetylase 6
      inhibitor, led to a synergistic increase in levels of acetylated alpha-tubulin.
      Aceroside VIII, paltyphyllone, and (-)-centrolobol synergistically enhanced the
      induction of apoptosis and growth inhibition by A452. Consistent with these
      results, A452 in combination with aceroside VIII, paltyphyllone, or (-)
      centrolobol was more potent than either drug alone for the induction of
      apoptosis. Together, these findings indicate that aceroside VIII is a specific
      histone deacetylase 6 inhibitor and points to a mechanism by which natural
      histone deacetylase 6-selective inhibitors may enhance the efficacy of other
      histone deacetylase 6 inhibitors in colon cancer cells. 

PMID- 25590369
TI  - Blockade of emodin on amyloid-beta 25-35-induced neurotoxicity in AbetaPP/PS1
      mice and PC12 cells through activation of the class III phosphatidylinositol 3
      kinase/Beclin-1/B-cell lymphoma 2 pathway.
AB  - Autophagy plays an important role in the pathogenesis of Alzheimer's disease. In
      the present study, the blockade mechanism of emodin on amyloid-beta 25-35-induced
      neurotoxicity was explored. Cell viability of PC12 cells was evaluated by the MTT
      assay and neuro damage by the lactate dehydrogenase leakage assay. Gene silencing
      by small interfering RNA, cDNA constructs and transfection, as well as Western
      blot were performed to assess protein expression levels. AbetaPP/PS1 mice were
      administered orally with emodin (50 mg/kg/day), and LC3-II positive cells in
      their brain cortex sections were detected by immunohistochemical staining. Emodin
      could significantly inhibit the LC3-I/LC3-II conversion ratio and cell viability
      while decreasing the lactate dehydrogenase level in AbetaPP/PS1 mice and PC12
      cells. LC3II positive cells in the cortex were decreased significantly by the
      treatment with both emodin and 3-methyladenine. Furthermore, emodin and 3
      methyladenine could increase B-cell lymphoma 2 while decreasing Beclin-1 and
      hVps34 expressions, which were induced by amyloid-beta 25-35. Small interfering
      gene silencing Beclin-1 and B-cell lymphoma 2 confirmed this signaling pathway.
      We also found that the phosphatidylinositol 3-kinase inhibitor LY294002 could
      block LC3-I/LC3-II conversion and increase B-cell lymphoma 2 while decreasing
      hVps34 and Beclin-1 expressions. The results suggest that the blockade of emodin
      on amyloid-beta 25-35-induced autophagy may occur via the activation of the class
      III phosphatidylinositol 3-kinase/Beclin-1/B-cell lymphoma 2 pathway. Our results
      provide confirmatory evidence for the application of emodin in the prevention and
      treatment of Alzheimer's disease. 

PMID- 25590370
TI  - Antispasmodic effects of myrrh due to calcium antagonistic effects in inflamed
      rat small intestinal preparations.
AB  - Myrrh is the oleo-gum resin of mainly Commiphora molmol and as a powdered
      substance, one compound in the traditional medicinal product Myrrhinil-Intest(r),
      which has been used for the treatment of unspecific, inflammatory intestinal
      disorders. The aim of the present study was to evaluate the antispasmodic effect
      of myrrh under healthy and inflamed conditions, and to evaluate a calcium
      antagonistic effect as a possible mode of action. Therefore, an ethanolic myrrh
      extract was tested for its effects on muscle tone and acetylcholine-induced
      contractions in untreated and inflamed rat ileum/jejunum preparations.
      Inflammation was experimentally induced by 2,4,6-trinitrobenzene sulfonic acid
      (10 mM, 30 min). Additionally, the effect of the calcium channel agonist Bay
      K8644 in the presence of varying myrrh extract concentrations was examined. Myrrh
      extract (0.99 mg/mL) suppressed the acetylcholine-induced contraction down to
      25.8 % in untreated and 15.2 % in inflamed preparations. Myrrh extract (0.15;
      0.25 and 0.35 mg/mL) induced a concentration-dependent rightward shift of the Bay
      K8644 concentration-response curve in untreated and inflamed preparations with a
      significant EC50 shift. Schild analysis resulted in a pA2 value of 0.93 for
      untreated preparations. Increasing myrrh extract concentrations induced a
      concentration-dependent decrease of the agonistic maximum effect in untreated and
      inflamed preparations down to 15.8 % and 25.8 %, respectively, for the highest
      concentration leading to a pD2 value of 0.58. Myrrh extract reduced intestinal
      muscle tone and acetylcholine-induced contraction of untreated and inflamed
      ileum/jejunum preparations based on dual calcium antagonism characterized by a
      right shift of the agonistic dose-response curve and a depression of the maximum
      effect. The resulting reduction of intestinal motility and spasmolytic effects
      provide a rationale for the symptom treatment of intestinal disorders such as
      irritable bowel syndrome. 

PMID- 25590371
TI  - Antiviral butyrolactones from the endophytic fungus Aspergillus versicolor.
AB  - Versicolactones A-D (1-4), four new butyrolactones, along with four known
      butyrolactones (5-8) were isolated from the fermentation products of the
      endophytic fungus Aspergillus versicolor. The structures of compounds 1-4,
      including absolute configuration, were elucidated by interpretation of the NMR
      and CD data. Compound 2 was further confirmed by single-crystal X-ray diffraction
      analysis. In particular, compound 1 is the first naturally occurring
      butyrolactone possessing an unusual 2-oxopropyl group. More importantly,
      compounds 1 and 8 displayed significant antitobacco mosaic virus activities with
      inhibition rates of 46.4 % and 35.4 %, even more potent than the positive control
      ningnanmycin (30.8 %). Compound 1 also showed moderate cytotoxicity against A549
      and MCF7 cells with IC50 values of 3.2 and 2.5 uM, respectively. 

PMID- 25590372
TI  - Symphonia globulifera, a widespread source of complex metabolites with potent
      biological activities.
AB  - Symphonia globulifera has been widely used in traditional medicine and has
      therefore been subjected to several phytochemical studies in the American and
      African continents. Interestingly, some disparities have been observed concerning
      its metabolic profile. Several phytochemical studies of S. globulifera have led
      to the identification of more than 40 compounds, including several polycyclic
      polyprenylated acylphloroglucinols. Biological evaluations have pointed out the
      promising biological activities of these secondary metabolites, mostly as
      antiparasitic or antimicrobial, confirming the traditional use of this plant. The
      purpose of this review is to describe the natural occurrence, botanical aspects,
      ethnomedicinal use, structure, and biogenesis, as well as biological activities
      of compounds isolated from this species according to their provenance. 

PMID- 25590374
TI  - Hupehenols A-E, selective 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1) inhibitors from Viburnum hupehense.
AB  - Five selective 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
      competitive inhibitors, hupehenols A-E (1-5), were isolated from Viburnum
      hupehense. The structure elucidation indicated that compounds 1-5 are new
      20,21,22,23,24,25,26,27-octanordammarane triterpenoids. Their structures were
      established on the basis of NMR spectroscopic and mass spectrometric analysis.
      Hupehenols A-E (1-5) showed inhibition against human 11beta-HSD1, with hupehenols
      B (2) and E (5) having IC50 values of 15.3 and 34.0 nM, respectively. Moreover,
      hupehenols C (3) and D (4) are highly selective inhibitors of human 11beta-HSD1
      when compared to murine 11beta-HSD1. 

PMID- 25590373
TI  - Activation of autophagy via Ca(2+)-dependent AMPK/mTOR pathway in rat notochordal
      cells is a cellular adaptation under hyperosmotic stress.
AB  - Nucleus pulposus (NP) cells experience hyperosmotic stress in spinal discs;
      however, how these cells can survive in the hostile microenvironment remains
      unclear. Autophagy has been suggested to maintain cellular homeostasis under
      different stresses by degrading the cytoplasmic proteins and organelles. Here, we
      explored whether autophagy is a cellular adaptation in rat notochordal cells
      under hyperosmotic stress. Hyperosmotic stress was found to activate autophagy in
      a dose- and time-dependent manner. SQSTM1/P62 expression was decreased as the
      autophagy level increased. Transient Ca(2+) influx from intracellular stores and
      extracellular space was stimulated by hyperosmotic stress. Activation of AMPK and
      inhibition of p70S6K were observed under hyperosmotic conditions. However,
      intercellular Ca(2+) chelation inhibited the increase of LC3-II and partly
      reversed the decrease of p70S6K. Hyperosmotic stress decreased cell viability and
      promoted apoptosis. Inhibition of autophagy led to SQSTM1/P62 accumulation,
      reduced cell viability, and accelerated apoptosis in notochordal cells under this
      condition. These evidences suggest that autophagy induction via the Ca(2+)
      dependent AMPK/mTOR pathway might occur as an adaptation mechanism for
      notochordal cells under hyperosmotic stress. Thus, activating autophagy might be
      a promising approach to improve viability of notochordal cells in intervertebral
      discs. 

PMID- 25590375
TI  - Genetically encoding lysine modifications on histone H4.
AB  - Post-translational modifications of proteins are important modulators of protein
      function. In order to identify the specific consequences of individual
      modifications, general methods are required for homogeneous production of
      modified proteins. The direct installation of modified amino acids by genetic
      code expansion facilitates the production of such proteins independent of the
      knowledge and availability of the enzymes naturally responsible for the
      modification. The production of recombinant histone H4 with genetically encoded
      modifications has proven notoriously difficult in the past. Here, we present a
      general strategy to produce histone H4 with acetylation, propionylation,
      butyrylation, and crotonylation on lysine residues. We produce homogeneous
      histone H4 containing up to four simultaneous acetylations to analyze the impact
      of the modifications on chromatin array compaction. Furthermore, we explore the
      ability of antibodies to discriminate between alternative lysine acylations by
      incorporating these modifications in recombinant histone H4. 

PMID- 25590376
TI  - Perspectives on oral pulmonary hypertension therapies recently approved by the
      U.S. Food and Drug Administration.
AB  - In the past 18 months, the U.S. Food and Drug Administration approved macitentan,
      riociguat, and treprostinil as oral agents for the treatment of pulmonary
      arterial hypertension (PAH); riociguat also became the first agent approved for
      the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). These new
      agents are welcome additional therapeutic options for PAH and CTEPH. However,
      their use can be complicated by potential drug interactions, adverse effects,
      dosing complexity, and cost. Macitentan, the newest endothelin receptor
      antagonist, showed significant benefits in a long-term event-driven trial of
      morbidity and mortality. Dosed once daily and with minimal liver toxicity, it has
      potential drug interactions with potent CYP 3A4 inhibitors and inducers, and can
      decrease hemoglobin levels. Riociguat is approved for PAH and clinically
      inoperable CTEPH to improve exercise capacity and functional status. Riociguat
      requires dose titration beginning with 1 mg up to 2.5 mg three times a day, as
      tolerated, and should be used with caution in patients with underlying risk
      factors for systemic hypotension. Oral treprostinil, approved to improve exercise
      capacity in PAH, is associated with gastrointestinal side effects and headaches
      that are often dose limiting. Doses can begin with 0.125 mg or 0.25 mg twice a
      day with gradual increases on up to a weekly basis, as tolerated. Thrice daily
      dosing and administration with a meal can improve tolerance. These newer agents
      represent advances, but their specific roles in relation to pre-existing
      therapies are undergoing further evaluation. Therefore, close collaboration with
      clinicians at centers with therapeutic expertise is highly recommended to
      optimize patient outcomes. 

PMID- 25590377
TI  - Unraveling the role of hydrogen peroxide in alpha-synuclein aggregation using an
      ultrasensitive nanoplasmonic probe.
AB  - Aggregation of alpha-Synuclein (alpha-Syn) in Lewy bodies is largely responsible
      for the demise and death of dopamine neurons. Oxidative stress associated with
      the aggregation-induced oxidative damage is considered as a possible origin of
      the toxicity. However, the cellular mechanism of H2O2 in the aggregation of alpha
      Syn remains a debate, i.e., whether the aggregation is caused by endogenously
      secreted or exogenous H2O2 from upstream. Here, we report on the development of
      an ultrasensitive plasmonic assay with a designed nanoplasmonic probe to unravel
      the role of H2O2 in the aggregation of alpha-Syn. The nanoplasmonic probe is
      composed of a Au nanoparticle with surface-attached double-stranded DNA and
      horseradish peroxidase (HRP). In the presence of H2O2, HRP initiates the
      polymerization of aniline, which in turn results in the in situ formation of a
      layer of conducting polymer on the nanoplasmonic probe. By monitoring the
      associated plasmonic response, we can sensitively detect H2O2 with a remarkably
      low detection limit of 8 nM. With this ultrasensitive plasmonic assay, we find
      that exogenous H2O2 plays a dominant role for the aggregation of alpha-Syn in
      vitro, whereas the contribution from endogenously secreted H2O2 is negligible. 

PMID- 25590378
TI  - The functional implications of common genetic variation in CYP3A5 and ABCB1 in
      human proximal tubule cells.
AB  - BACKGROUND: Calcineurin inhibitors (CNIs) are the primary immunosuppressive drugs
      used in solid organ transplantation but are associated with the development of
      histological lesions leading to kidney failure. CNIs are metabolized by CYP3A and
      excreted by not only P-glycoprotein (P-gp) (ABCB1) in the gut and liver, but also
      by proximal tubule cells (PTCs) in the kidney. Multiple studies have demonstrated
      the importance of genetic variation in CYP3A5 and ABCB1 for CNI disposition and
      nephrotoxicity. The present study was designed to study the functional
      implication of variation in these two genes in human PTCs. METHODS: A technique
      was developed to culture cells from renal tissue obtained from renal graft
      recipients by routine kidney biopsy. Primary cells were immortalized, subcloned,
      and then characterized for specific PTC markers (AQP1, CD13, brush border
      morphology) and donor CYP3A5(rs776746)/ABCB1(rs1045642) genotype. We then
      selected specific sets of confirmed conditionally immortalized PTCs (ciPTC)
      according to different combinations of the aforementioned genetic variants.
      Quantitative real-time polymerase chain reaction, Western blot, and
      immunohistochemistry were performed for studying CYP3A5 and ABCB1 expression.
      CYP3A5 activity was assessed by differential midazolam (MDZ) hydroxylation and P
      gp (ABCB1 product) activity by a calcein efflux assay. Differential drug
      metabolism between cell lines was assessed by tacrolimus disappearance over 24 h.
      RESULTS: Cell lines were generated from 27 out of 38 tissue samples. On the basis
      of genotype and PTC biomarkers, 11 subclones were selected. In vitro PTC
      morphology with brush border microvilli was confirmed. CYP3A5*1 carriers had
      increased 1-OH/4-OH MDZ formation versus homozygous *3 carriers (mean: 2.36 (95%
      CI:1.11-3.40) vs 0.88 (95% CI:0.48-1.27); p < 0.05). P-gp activity was confirmed
      by calcein accumulation (mean 38.6%; 95% CI:32.8-44.4%), which was higher in cell
      lines with the ABCB1 3435TT than the 3435CC/CT genotype (46.2% vs 35.5%; 95%
      CI:28.7-42.2%). Tacrolimus disappearance was about two-fold higher in cell lines
      with the combined CYP3A5*1/ABCB1 3435TT genotype versus other genotype
      combinations. CONCLUSION: Biopsy-derived and immortalized human PTC cell lines
      demonstrate functional expression of genes involved in CNI metabolism.
      Differences in functional expression were detected according to common genetic
      variants in CYP3A5 and ABCB1. The studied genetic variants had a significant
      impact on in vitro tacrolimus metabolism. In particular, ciPTC with the combined
      CYP3A5*1/ABCB1 3435TT genotype demonstrated higher tacrolimus disappearance
      versus ciPTCs with a different pharmacogenetic profile. This in vitro model
      stresses the importance of the incorporation of pharmacogenetic variation in
      studies involved in (renal) drug disposition.

PMID- 25590379
TI  - Genotoxic and biochemical changes in Baccharis trimera induced by coal
      contamination.
AB  - The processing and combustion of coal in thermal power plants release
      anthropogenic chemicals into the environment. Baccharis trimera is a common plant
      used in folk medicine that grows readily in soils degraded by coal mining
      activities. This shrub bioaccumulates metals released into the environment, and
      thus its consumption may be harmful to health. The purpose of this study was to
      investigate the phytochemical profile, antioxidant capacity (DPPH), genotoxic
      (comet assay) and mutagenic potential (CBMN-cyt) in V79 cells of B. trimera
      aqueous extracts in the coal-mining region of Candiota (Bt-AEC), and in Bage, a
      city that does not experience the effects of exposure to coal (Bt-AEB, a
      reference site). In the comet assay, only Bt-AEC was genotoxic at the highest
      doses (0.8mg/mL and 1.6mg/mL), compared to the control. For extracts from both
      areas, mutagenic effects were observed at higher concentrations compared to the
      control. The cell damage parameters were significantly high in both extracts;
      however, more striking values were observed for Bt-AEC, up to the dose of
      0.8mg/mL. In chemical analysis, no variation was observed in the contents of
      flavonoids and phenolic compounds, neither the antioxidant activity, which may
      suggest that DNA damage observed in V79 cells was induced by the presence of coal
      contaminants absorbed by the plant.

PMID- 25590380
TI  - Stereological and flow cytometry characterization of leukocyte subpopulations in
      models of transient or permanent cerebral ischemia.
AB  - Microglia activation, as well as extravasation of haematogenous macrophages and
      neutrophils, is believed to play a pivotal role in brain injury after stroke.
      These myeloid cell subpopulations can display different phenotypes and functions
      and need to be distinguished and characterized to study their regulation and
      contribution to tissue damage. This protocol provides two different methodologies
      for brain immune cell characterization: a precise stereological approach and a
      flow cytometric analysis. The stereological approach is based on the optical
      fractionator method, which calculates the total number of cells in an area of
      interest (infarcted brain) estimated by a systematic random sampling. The second
      characterization approach provides a simple way to isolate brain leukocyte
      suspensions and to characterize them by flow cytometry, allowing for the
      characterization of microglia, infiltrated monocytes and neutrophils of the
      ischemic tissue. In addition, it also details a cerebral ischemia model in mice
      that exclusively affects brain cortex, generating highly reproducible infarcts
      with a low rate of mortality, and the procedure for histological brain processing
      to characterize infarct volume by the Cavalieri method. 

PMID- 25590382
TI  - NMR crystallography for structural characterization of oxovanadium(V) complexes:
      deriving coordination geometry and detecting weakly coordinated ligands at atomic
      resolution in the solid state.
AB  - NMR crystallography is an emerging method for atomic-resolution structural
      analysis of ubiquitous vanadium(V) sites in inorganic and bioinorganic complexes
      as well as vanadium-containing proteins. NMR crystallography allows for
      characterization of vanadium(V) containing solids, based on the simultaneous
      measurement of (51)V-(15)N internuclear distances and anisotropic spin
      interactions, described by (13)C, (15)N, and (51)V chemical shift anisotropy and
      (51)V electric field gradient tensors. We show that the experimental (51)V,
      (13)C, and (15)N NMR parameters are essential for inferring correct coordination
      numbers and deriving correct geometries in density functional theory (DFT)
      calculations, particularly in the absence of single-crystal X-ray structures. We
      first validate this approach on a structurally known vanadium(V) complex, ((15)N
      salicylideneglycinate)-(benzhydroxamate)oxovanadium(V), VO(15)NGlySalbz. We then
      apply this approach to derive the three-dimensional structure of (methoxo)((15)N
      salicylidene-glycinato)oxovanadium(V) with solvated methanol,
      [VO((15)NGlySal)(OCH3)].(CH3OH). This is a representative complex with
      potentially variable coordination geometry depending on the solvation level of
      the solid. The solid material containing molecules of CH3OH, formally expressed
      as [VO((15)NGlySal)(OCH3)].(CH3OH), is found to have one molecule of CH3OH weakly
      coordinated to the vanadium. The material is therefore best described as
      [VO((15)NGlySal)(OCH3)(CH3OH)] as deduced by the combination of multinuclear
      solid-state NMR experiments and DFT calculations. The approach reported here can
      be used for structural analysis of systems that are not amenable to single
      crystal X-ray diffraction characterization and which can contain weakly
      associated solvents. 

PMID- 25590381
TI  - Synthesis, molecular docking and anti-inflammatory screening of novel quinoline
      incorporated pyrazole derivatives using the Pfitzinger reaction II.
AB  - In continuation of our study of novel quinolines with anti-inflammatory activity
      using the Pfitzinger reaction, several new quinoline derivatives were synthesized
      and tested for their anti-inflammatory and ulcerogenic effect. A docking study on
      the COX-2 binding pocket was carried out for the target compounds to rationalize
      the possible selectivity of them against COX-2 enzyme. The most active compounds
      (5a, 8a and 11a) were found to be superior to celecoxib. Compound 11a
      demonstrated the highest anti-inflammatory activity as well as the best binding
      profiles into the COX-2 binding site. Moreover, compounds 9c, 9e, 10a and 11a
      were devoid of ulcerogenic activity. 

PMID- 25590384
TI  - Radiographic findings after treatment with balloon brachytherapy accelerated
      partial breast irradiation.
AB  - The use of accelerated partial breast irradiation (APBI) following breast
      conserving surgery is rapidly gaining popularity as an alternative to whole
      breast irradiation (WBI) in selected patients with early-stage breast cancer.
      Although data on the long-term effectiveness and safety of APBI accelerated
      partial breast irradiation are still being gathered, the shorter treatment course
      and narrowed radiation target of APBI accelerated partial breast irradiation
      provide an attractive alternative for carefully selected patients. These patients
      include those with relatively small tumors (<=3 cm), negative or close margins,
      and negative sentinel lymph nodes. Possible long-term complications include
      telangiectasia and the development of a palpable mass at the lumpectomy site.
      Mammographic findings in patients who have undergone APBI accelerated partial
      breast irradiation are distinct from those in patients who have undergone
      conventional WBI whole-breast irradiation . The most common post-APBI accelerated
      partial breast irradiation radiographic findings include formation of seromas at
      the lumpectomy site, focal parenchymal changes such as increased trabeculation
      and parenchymal distortion, fat necrosis, and skin changes such as thickening or
      retraction. Given the continued evolution of breast cancer treatment, it is
      important that radiologists have a comprehensive understanding of APBI
      accelerated partial breast irradiation in terms of rationale, patient selection
      criteria, common postprocedural radiographic findings (and how they differ from
      post-WBI whole-breast irradiation findings), and advantages and potential
      complications.

PMID- 25590385
TI  - The right atrium: gateway to the heart--anatomic and pathologic imaging findings.
AB  - Knowledge of right atrial anatomic and pathologic imaging findings and associated
      clinical symptoms is important to avoid false-positive diagnoses and missed
      findings. Complete evaluation of the heart often requires a multimodality
      approach that includes radiography, echocardiography, computed tomography (CT),
      magnetic resonance (MR) imaging, and invasive angiography. In general, CT
      provides the highest spatial resolution of these modalities at the cost of
      radiation exposure to the patient. Echocardiography and MR imaging offer
      complementary and detailed information for functional evaluation without added
      radiation exposure. The advantages and disadvantages of each modality for the
      evaluation of right atrial anatomic structure, size, and pathologic findings are
      discussed. Cardiac MR imaging is the reference standard for evaluation of right
      atrial size and volume but often is too time consuming and resource intensive to
      perform in routine clinical practice. Therefore, established reference ranges for
      two-dimensional transthoracic echocardiography are often used. Right atrial
      pathologic findings can be broadly categorized into (a) congenital anomalies (cor
      triatriatum dexter, Ebstein anomaly, and aneurysm), (b) disorders of volume
      (tricuspid regurgitation, pathologic mimics such as a pseudoaneurysm, and atrial
      septal defect), (c) disorders of pressure (tricuspid stenosis, restrictive
      cardiomyopathy, and constrictive pericarditis), and (d) masses (pseudomasses,
      thrombus, lipomatous hypertrophy of the interatrial septum, lipoma, myxoma,
      sarcoma, and metastatic disease). Familiarity with each pathologic entity and its
      treatment options is essential to ensure that appropriate imaging modalities are
      selected. Online supplemental material is available for this article.

PMID- 25590386
TI  - Bronchial arteries: anatomy, function, hypertrophy, and anomalies.
AB  - The two main sources of blood supply to the lungs and their supporting structures
      are the pulmonary and bronchial arteries. The bronchial arteries account for 1%
      of the cardiac output but can be recruited to provide additional systemic
      circulation to the lungs in various acquired and congenital thoracic disorders.
      An understanding of bronchial artery anatomy and function is important in the
      identification of bronchial artery dilatation and anomalies and the formulation
      of an appropriate differential diagnosis. Visualization of dilated bronchial
      arteries at imaging should alert the radiologist to obstructive disorders that
      affect the pulmonary circulation and prompt the exclusion of diseases that
      produce or are associated with pulmonary artery obstruction, including chronic
      infectious and/or inflammatory processes, chronic thromboembolic disease, and
      congenital anomalies of the thorax (eg, proximal interruption of the pulmonary
      artery). Conotruncal abnormalities, such as pulmonary atresia with ventricular
      septal defect, are associated with systemic pulmonary supply provided by aortic
      branches known as major aortopulmonary collaterals, which originate in the region
      of the bronchial arteries. Bronchial artery malformation is a rare left-to-right
      or left-to-left shunt characterized by an anomalous connection between a
      bronchial artery and a pulmonary artery or a pulmonary vein, respectively.
      Bronchial artery interventions can be used successfully in the treatment of
      hemoptysis, with a low risk of adverse events. Multidetector computed tomography
      helps provide a vascular road map for the interventional radiologist before
      bronchial artery embolization.

PMID- 25590387
TI  - US of gastrointestinal tract disease.
AB  - The potential use of ultrasonography (US) in evaluating gut disease has been
      underappreciated in most diagnostic imaging departments in North America. The
      impression that US has a questionable role in bowel assessment is related to the
      operator-dependent nature of the modality, the technical challenges of performing
      bowel US examinations, and the lack of familiarity of radiologists and
      technologists with the US appearances of normal and abnormal bowel. However, with
      development of technical experience by the sonographer and integration of a
      clinical focus at patient evaluation, US can become a powerful tool for bowel
      assessment. Unlike computed tomography and magnetic resonance imaging, it
      provides a widely available, noninvasive, inexpensive method for evaluating the
      gut without the use of ionizing radiation. These factors are of particular
      importance in young patients and those who require recurrent follow-up imaging.
      Because US is performed with real-time imaging, the modality also allows the
      sonographer to view and assess the motility properties of the bowel, a feature
      that has not been previously used to its full potential. Color Doppler US can
      yield useful information about mural vascularity in bowel disease when used in
      conjunction with gray-scale findings and clinical symptoms. Radiologists should
      be familiar with the static and dynamic US appearances of the normal and abnormal
      bowel, recognize features of various pathologic conditions, and understand
      potential errors at imaging interpretation. Online supplemental material is
      available for this article.

PMID- 25590388
TI  - Invited commentary on "US of gastrointestinal tract disease".

PMID- 25590389
TI  - Hematologic malignancies of the liver: spectrum of disease.
AB  - The incidence of hematologic malignancies and their extranodal manifestations is
      continuously increasing. Previously unsuspected hepatic involvement in
      hematologic malignancies such as Hodgkin disease and non-Hodgkin lymphoma,
      posttransplant lymphoproliferative disorder, myeloid sarcoma (chloroma), multiple
      myeloma, Castleman disease, and lymphohistiocytosis may be seen by radiologists.
      Although the imaging features of more common hepatic diseases such as
      hepatocellular carcinoma, metastases, and infection may overlap with those of
      hepatic hematologic malignancies, combining the imaging features with clinical
      manifestations and laboratory findings can facilitate correct diagnosis. Clinical
      features that suggest a hematologic neoplasm as the cause of liver lesions
      include a young patient (<40 years of age), no known history of cancer, abnormal
      bone marrow biopsy results, fever of unknown origin, and night sweats. Imaging
      features that suggest hematologic malignancy include hepatosplenomegaly or
      splenic lesions, vascular encasement by a tumor without occlusion or thrombosis,
      an infiltrating mass at the hepatic hilum with no biliary obstruction, and
      widespread adenopathy above and below the diaphragm. Familiarity with the imaging
      features of hepatic hematologic malignancies permits correct provisional
      diagnosis and may influence therapeutic management. For example, when biopsy is
      performed, core biopsy may be needed in addition to fine-needle aspiration so
      that the tissue architecture of the neoplasm can be discerned. The predominant
      treatment of hematologic malignancies is chemotherapy or radiation therapy rather
      than surgery. Online supplemental material is available for this article.

PMID- 25590390
TI  - Nonvascular post-liver transplantation complications: from US screening to cross
      sectional and interventional imaging.
AB  - Orthotopic liver transplantation is becoming an increasingly routine procedure
      for a variety of benign and malignant diseases of the liver and biliary system.
      Continued improvements in surgical techniques and post-transplantation
      immunosuppression regimens have resulted in better graft and patient survival. A
      number of potentially treatable nonvascular complications of liver
      transplantation are visible at imaging, and accurate diagnosis of these
      complications allows patients to benefit from potential treatment options.
      Biliary complications include stricture (anastomotic and nonanastomotic), leak,
      biloma formation, and development of intraductal stones. Pathologic conditions,
      including hepatitis C infection, hepatocellular carcinoma, hepatic steatosis, and
      primary sclerosing cholangitis, may recur after liver transplantation. Transplant
      patients are at increased risk for developing de novo malignancy, including post
      transplantation lymphoproliferative disorder, which results from
      immunosuppression. Patients are also at increased risk for systemic infection
      from immunosuppression, and patients with hepatic artery and biliary
      complications are at increased risk for liver abscess. Transplant recipients are
      typically followed with serial liver function testing; abnormal serum liver
      function test results may be the first indication that there is a problem with
      the transplanted liver. Ultrasonography is typically the first imaging test
      performed to try to identify the cause of abnormal liver function test results.
      Computed tomography, magnetic resonance imaging, angiography, and/or
      cholangiography may be necessary for further evaluation. Accurately diagnosing
      nonvascular complications of liver transplantation that are visible at imaging is
      critically important for patients to benefit from appropriate treatment.

PMID- 25590391
TI  - Dysphagia revisited: common and unusual causes.
AB  - Dysphagia is a common clinical problem whose prevalence is increasing with the
      aging population in the United States. The term dysphagia is commonly used to
      describe subjective awareness of swallowing difficulty during the passage of a
      bolus from the mouth to the stomach or the perception of obstruction during
      swallowing. Dysphagia may be further classified as oropharyngeal or substernal,
      depending on the location of this sensation. It can be due to benign or malignant
      structural lesions, esophageal motility abnormalities, oropharyngeal dysfunction
      (including aspiration), neuromuscular disorders, or postsurgical changes and is
      also associated with gastroesophageal reflux disease. Pathologic conditions of
      the oral cavity, pharynx, esophagus, and proximal stomach can manifest with
      dysphagia. Imaging remains the preferred method for evaluating patients with
      dysphagia, and dysphagia is an increasingly encountered indication for radiologic
      evaluation. Fluoroscopic studies, including the modified barium swallow and
      esophagography in particular, are often used in the assessment of patients with
      dysphagia, and the techniques used for these studies should be tailored to the
      patient's needs. Fluoroscopic studies can be used to evaluate the esophagus for
      structural abnormalities (eg, webs, diverticula, strictures, masses) and to
      assess function (eg, the swallowing mechanism and esophageal motility). Knowledge
      of the imaging spectrum of disease entities that may cause dysphagia and thorough
      radiologic assessment with a tailored approach may help avoid misdiagnosis.

PMID- 25590392
TI  - Appendicitis: atypical and challenging CT appearances.

PMID- 25590393
TI  - CT and MR imaging for evaluation of cystic renal lesions and diseases.
AB  - Cystic renal lesions are commonly encountered in abdominal imaging. Although most
      cystic renal lesions are benign simple cysts, complex renal cysts, infectious
      cystic renal disease, and multifocal cystic renal disease are also common
      phenomena. The Bosniak classification system provides a useful means of
      categorizing cystic renal lesions but places less emphasis on their underlying
      pathophysiology. Cystic renal diseases can be categorized as focal, multifocal,
      or infectious lesions. Diseases that manifest with focal lesions, such as cystic
      renal cell carcinoma, mixed epithelial and stromal tumor, and cystic nephroma,
      are often difficult to differentiate but have differing implications for follow
      up after resection. Multifocal cystic renal lesions can be categorized as
      acquired or heritable. Acquired entities, such as glomerulocystic kidney disease,
      lithium-induced nephrotoxicity, acquired cystic kidney disease, multicystic
      dysplastic kidney, and localized cystic renal disease, often have distinct
      imaging and clinical features that allow definitive diagnosis. Heritable
      diseases, such as autosomal dominant polycystic kidney disease, von Hippel-Lindau
      disease, and tuberous sclerosis, are usually easily identified and have various
      implications for patient management. Infectious diseases have varied imaging
      appearances, and the possibility of infection must not be overlooked when
      assessing a cystic renal lesion. A thorough understanding of the spectrum of
      cystic renal disease will allow the radiologist to make a more specific diagnosis
      and provide the clinician with optimal recommendations for further diagnostic
      testing and follow-up imaging.

PMID- 25590395
TI  - Extrapulmonary small cell carcinoma: imaging features with radiologic-pathologic
      correlation.
AB  - Extrapulmonary small cell carcinoma (EPSCC) refers to small cell carcinoma
      arising outside of the lungs. EPSCC extrapulmonary small cell carcinoma is a rare
      aggressive neoplasm, representing a minority of all small cell carcinomas.
      Despite its uncommon occurrence, EPSCC extrapulmonary small cell carcinoma has
      been described in nearly every organ, most commonly in the gastrointestinal and
      genitourinary systems. As such, it is important for radiologists to be aware of
      the entity. Although imaging is neither sensitive nor specific for EPSCC
      extrapulmonary small cell carcinoma , it plays an important role by helping
      exclude metastases from a primary pulmonary tumor, establish tumor staging, and
      assess response to therapy. EPSCC extrapulmonary small cell carcinoma is
      diagnosed by demonstrating pathologic features of small cell carcinoma in an
      extrapulmonary site. There are two ways to stage EPSCC extrapulmonary small cell
      carcinoma . One method uses the Veterans Administration Lung Study Group system
      developed for small cell lung cancer that allocates patients into limited or
      extensive disease categories. The second approach is the American Joint Committee
      on Cancer tumor-node-metastasis system applied to other tumor subtypes arising
      from the same organ. Because of its rare and varied manifestations, the most
      effective treatment for EPSCC extrapulmonary small cell carcinoma has not been
      established. Current management recommendations are derived from retrospective
      studies and single-institution experiences or are extrapolated from small cell
      lung cancer data. Regardless of therapy, overall survival rates are poor, with 5
      year survival rates around 13%. To help radiologists increase their familiarity
      with EPSCC extrapulmonary small cell carcinoma , this article provides (a) a
      background for EPSCC extrapulmonary small cell carcinoma based on the literature
      and (b) a pictorial review of EPSCC extrapulmonary small cell carcinoma in
      multiple organs, with radiologic-pathologic correlation.

PMID- 25590396
TI  - Dynamic high-resolution US of ankle and midfoot ligaments: normal anatomic
      structure and imaging technique.
AB  - The ankle is the most frequently injured major joint in the body, and ankle
      sprains are frequently encountered in individuals playing football, basketball,
      and other team sports, in addition to occurring in the general population.
      Imaging plays a crucial role in the evaluation of ankle ligaments. Magnetic
      resonance imaging has been proven to provide excellent evaluation of ligaments
      around the ankle, with the ability to show associated intraarticular
      abnormalities, joint effusion, and bone marrow edema. Ultrasonography (US)
      performed with high-resolution broadband linear-array probes has become
      increasingly important in the assessment of ligaments around the ankle because it
      is low cost, fast, readily available, and free of ionizing radiation. US can
      provide a detailed depiction of normal anatomic structures and is effective for
      evaluating ligament integrity. In addition, US allows the performance of dynamic
      maneuvers, which may contribute to increased visibility of normal ligaments and
      improved detection of tears. In this article, the authors describe the US
      techniques for evaluation of the ankle and midfoot ligaments and include a brief
      review of the literature related to their basic anatomic structures and US of
      these structures. Short video clips showing dynamic maneuvers and dynamic real
      time US of ankle and midfoot structures and their principal pathologic patterns
      are included as supplemental material. Use of a standardized imaging technique
      may help reduce the intrinsic operator dependence of US. Online supplemental
      material is available for this article.

PMID- 25590397
TI  - High-resolution US and MR imaging of peroneal tendon injuries.
AB  - Injuries of the peroneal tendon complex are common and should be considered in
      every patient who presents with chronic lateral ankle pain. These injuries occur
      as a result of trauma (including ankle sprains), in tendons with preexisting
      tendonopathy, and with repetitive microtrauma due to instability. The peroneus
      brevis and peroneus longus tendons are rarely torn simultaneously. Several
      anatomic variants, including a flat or convex fibular retromalleolar groove,
      hypertrophy of the peroneal tubercle at the lateral aspect of the calcaneus, an
      accessory peroneus quartus muscle, a low-lying peroneus brevis muscle belly, and
      an os peroneum, may predispose to peroneal tendon injuries. High-resolution 1.5-T
      and 3-T magnetic resonance (MR) imaging with use of dedicated extremity coils and
      high-resolution ultrasonography (US) with high-frequency linear transducers and
      dynamic imaging are proved to adequately depict the peroneal tendons for
      evaluation and can aid the orthopedic surgeon in injury management. An
      understanding of current treatment approaches for partial- and full-thickness
      peroneal tendon tears, subluxation and dislocation of these tendons with superior
      peroneal retinaculum (SPR) injuries, intrasheath subluxations, and peroneal
      tendonopathy and tenosynovitis can help physicians achieve a favorable outcome.
      Patients with low functional demands do well with conservative treatment, while
      those with high functional demands may benefit from surgery if nonsurgical
      treatment is unsuccessful. Radiologists should recognize the normal anatomy and
      specific pathologic conditions of the peroneal tendons at US and MR imaging and
      understand the various treatment options for peroneal tendon and SPR superior
      peroneal retinaculum injuries. Online supplemental material is available for this
      article.

PMID- 25590394
TI  - Ontology-based image navigation: exploring 3.0-T MR neurography of the brachial
      plexus using AIM and RadLex.
AB  - Disorders of the peripheral nervous system have traditionally been evaluated
      using clinical history, physical examination, and electrodiagnostic testing. In
      selected cases, imaging modalities such as magnetic resonance (MR) neurography
      may help further localize or characterize abnormalities associated with
      peripheral neuropathies, and the clinical importance of such techniques is
      increasing. However, MR image interpretation with respect to peripheral nerve
      anatomy and disease often presents a diagnostic challenge because the relevant
      knowledge base remains relatively specialized. Using the radiology knowledge
      resource RadLex(r), a series of RadLex queries, the Annotation and Image Markup
      standard for image annotation, and a Web services-based software architecture,
      the authors developed an application that allows ontology-assisted image
      navigation. The application provides an image browsing interface, allowing users
      to visually inspect the imaging appearance of anatomic structures. By interacting
      directly with the images, users can access additional structure-related
      information that is derived from RadLex (eg, muscle innervation, muscle
      attachment sites). These data also serve as conceptual links to navigate from one
      portion of the imaging atlas to another. With 3.0-T MR neurography of the
      brachial plexus as the initial area of interest, the resulting application
      provides support to radiologists in the image interpretation process by allowing
      efficient exploration of the MR imaging appearance of relevant nerve segments,
      muscles, bone structures, vascular landmarks, anatomic spaces, and entrapment
      sites, and the investigation of neuromuscular relationships.

PMID- 25590398
TI  - Congenital abnormalities of the posterior fossa.
AB  - The frequency and importance of the evaluation of the posterior fossa have
      increased significantly over the past 20 years owing to advances in neuroimaging.
      Nowadays, conventional and advanced neuroimaging techniques allow detailed
      evaluation of the complex anatomic structures within the posterior fossa. A wide
      spectrum of congenital abnormalities has been demonstrated, including
      malformations (anomalies due to an alteration of the primary developmental
      program caused by a genetic defect) and disruptions (anomalies due to the
      breakdown of a structure that had a normal developmental potential). Familiarity
      with the spectrum of congenital posterior fossa anomalies and their well-defined
      diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and
      correct genetic counseling. The authors discuss the spectrum of posterior fossa
      malformations and disruptions, with emphasis on neuroimaging findings (including
      diagnostic criteria), neurologic presentation, systemic involvement, prognosis,
      and risk of recurrence.

PMID- 25590399
TI  - Postoperative imaging of the orbital contents.
AB  - Ophthalmologists perform a wide array of interventions on the orbital contents.
      The surgical treatment of glaucoma, cataracts, retinal detachment, and ocular
      trauma or malignancy results in alteration of the standard anatomy, which is
      often readily evident at radiologic examinations. The ability to accurately
      recognize the various imaging manifestations after orbital surgery is critical
      for radiologists to avoid misdiagnosis. Of particular importance is familiarity
      with the numerous types of implanted devices, such as glaucoma drainage devices,
      orbital implants, and eyelid weights. Although knowledge of patients' surgical
      history is helpful, this information is often not available at the time of
      interpretation. Fortunately, there are characteristic posttreatment findings that
      enable diagnosis. The imaging features of the most commonly performed
      ophthalmologic procedures are highlighted, with emphasis on computed tomography
      and magnetic resonance (MR) imaging, because they are currently the primary
      modalities involved in evaluating the orbits. Glaucoma drainage devices and
      orbital implants after enucleation are two of the more pertinent implanted
      devices because their composition has substantially evolved over the past 2
      decades, which affects their imaging appearance. Some devices, such as the
      Baerveldt Glaucoma Implant and platinum-weighted eyelid implants, may distort
      radiologic images. The MR imaging safety profiles of numerous implanted devices
      are also reported.

PMID- 25590401
TI  - Strategic planning and radiology practice management in the new health care
      environment.
AB  - Current comprehensive health care reform in the United States demands that policy
      makers, insurers, providers, and patients work in reshaping the health care
      system to deliver care that is both more affordable and of higher quality. A
      tectonic shift is under way that runs contrary to the traditional goal of
      radiology groups to perform and interpret large numbers of imaging examinations.
      In fact, radiology service requisitions now must be evaluated for their
      appropriateness, possibly resulting in a reduction in the number of imaging
      studies performed. To be successful, radiology groups will have to restructure
      their business practices and strategies to align with the emerging health care
      paradigm. This article outlines a four-stage strategic framework that has aided
      corporations in achieving their goals and that can be readily adapted and applied
      by radiologists. The four stages are (a) definition and articulation of a
      purpose, (b) clear definition of strategic goals, (c) prioritization of specific
      strategic enablers, and (d) implementation of processes for tracking progress and
      enabling continuous adaptation. The authors provide practical guidance for
      applying specific tools such as analyses of strengths, weaknesses, opportunities,
      and threats (so-called SWOT analyses), prioritization matrices, and balanced
      scorecards to accomplish each stage. By adopting and applying these tools within
      the strategic framework outlined, radiology groups can position themselves to
      succeed in the evolving health care environment.

PMID- 25590400
TI  - Rabies encephalitis.

PMID- 25590402
TI  - Abdominal aortic aneurysms revisited: MDCT with multiplanar reconstructions for
      identifying indicators of instability in the pre- and postoperative patient.
AB  - Rupture of an abdominal aortic aneurysm is commonly a fatal event. Multidetector
      computed tomographic (CT) signs of frank aortic rupture are usually readily
      apparent and widely understood. However, diagnosing an impending aortic rupture
      on the basis of imaging findings can prove more difficult. CT is the primary
      modality used for serial imaging in patients with aortic aneurysm and may show
      findings indicative of aortic instability. Therefore, it is critical that
      radiologists be familiar with the CT findings of aortic instability to avert the
      potential complications of hemorrhage, end organ or limb ischemia, and death.
      Various preoperative CT indicators have been previously described in both
      research investigations and review articles. A large baseline aneurysm size and a
      rapid increase in size over time are associated with a higher risk for rupture.
      The importance of obtaining accurate measurements with multiplanar
      reconstructions and the role of new semiautomated tools for obtaining accurate,
      reproducible measurements are discussed. Additional CT findings that reflect
      aortic aneurysm instability include luminal expansion with lysis of thrombus,
      intramural hemorrhage (ie, the crescent sign), periaortic hemorrhage, a
      penetrating atherosclerotic ulcer, and contained rupture (ie, the draped aorta
      sign). After open or endovascular aneurysm repair, CT is routinely used to
      monitor for graft complications. In this setting, radiologists should understand
      that the presence of an endoluminal stent or surgical graft does not preclude
      aortic rupture. Online supplemental material is available for this article.

PMID- 25590403
TI  - Pleomorphic liposarcoma of the inferior vena cava.

PMID- 25590404
TI  - Holoprosencephaly: a survey of the entity, with embryology and fetal imaging.
AB  - Structural malformations of the brain are an important cause of childhood
      mortality and morbidity, with the latter having long-term financial and
      psychosocial implications for the affected child and family. Holoprosencephaly
      (HPE) is a severe brain malformation characterized by abnormal cleavage of the
      prosencephalon in the 5th gestational week. Aprosencephaly and atelencephaly
      occur earlier because of failure in the formation of the prosencephalon and
      telencephalon, respectively. The HPE holoprosencephaly spectrum classically
      includes alobar, semilobar, and lobar forms, although there are no clear-cut
      defining features. The middle interhemispheric variant (MIH), also known as
      syntelencephaly, is classified as a variant of HPE holoprosencephaly with midline
      interhemispheric fusion. Other conditions sometimes included in the spectrum of
      HPE holoprosencephaly include septo-optic dysplasia (SOD); "minimal" HPE
      holoprosencephaly , which is associated with subtle craniofacial malformations
      and mild developmental delay; and microform HPE holoprosencephaly , which by
      definition excludes brain involvement. The focus of this article will be on the
      spectrum of findings visible in fetal manifestation of the HPE holoprosencephaly
      spectrum. Brain embryology; the imaging characteristics, epidemiology, and
      embryology of HPE; and the more common associated anomalies, particularly those
      of the face ("the face predicts the brain") are reviewed. Recognition of these
      anomalies is important for accurate parental counseling, since the prognosis is
      poor but not invariably lethal; children with the milder forms may live well into
      their teens with severe developmental delays, endocrine dysfunction, and
      disrupted homeostasis. Available data on outcome in surviving children are
      summarized. Illustrative fetal ultrasonographic and magnetic resonance images are
      presented with clinical, autopsy, and postnatal imaging correlation.

PMID- 25590405
TI  - Give and take in the radiology workplace.

PMID- 25590407
TI  - Carney complex: one more entity with skin and bone manifestations.

PMID- 25590408
TI  - Dorsal thoracic arachnoid web: another intradural entity with ventral cord
      displacement.

PMID- 25590409
TI  - Preprocedural CT Evaluation of Transcatheter Aortic Valve Replacement: What the
      Radiologist Needs to Know-Erratum.

PMID- 25590410
TI  - Techniques for creating video content for radiology education-erratum.

PMID- 25590411
TI  - Designer germanium quantum dot phototransistor for near infrared optical
      detection and amplification.
AB  - We demonstrated a unique CMOS approach for the production of a high-performance
      germanium (Ge) quantum dot (QD) metal-oxide-semiconductor phototransistor. In the
      darkness, low off-state leakage (Ioff ~ 0.27 pA MUm(-2)), a high on-off current
      ratio (Ion/Ioff ~ 10(6)), and good switching behaviors (subthreshold swing of 175
      mV/dec) were measured on our Ge-QD phototransistor at 300 K, indicating good
      hetero-interfacial quality of the Ge-on-Si. Illumination makes a significant
      enhancement in the drain current of Ge QD phototransistors when biased at both
      the on- and off-states, which is a great benefit from Ge QD-mediated
      photoconductive and photovoltaic effects. The measured photocurrent-to-dark
      current ratio (Iphoto/Idark) and the photoresponsivities from the Ge QD
      phototransistor are as high as 4.1 * 10(6) and 1.7 A W(-1), respectively, under
      an incident power of 0.9 mW at 850 nm illumination. A superior external quantum
      efficiency of 240% and a very fast temporal response time of 1.4 ns suggest that
      our Ge QD MOS phototransistor offers great promise as optical switches and
      transducers for Si-based optical interconnects.

PMID- 25590412
TI  - An ex vivo model to study hormone action in the human breast.
AB  - The study of hormone action in the human breast has been hampered by lack of
      adequate model systems. Upon in vitro culture, primary mammary epithelial cells
      tend to lose hormone receptor expression. Widely used hormone receptor positive
      breast cancer cell lines are of limited relevance to the in vivo situation. Here,
      we describe an ex vivo model to study hormone action in the human breast. Fresh
      human breast tissue specimens from surgical discard material such as reduction
      mammoplasties or mammectomies are mechanically and enzymatically digested to
      obtain tissue fragments containing ducts and lobules and multiple stromal cell
      types. These tissue microstructures kept in basal medium without growth factors
      preserve their intercellular contacts, the tissue architecture, and remain
      hormone responsive for several days. They are readily processed for RNA and
      protein extraction, histological analysis or stored in freezing medium.
      Fluorescence activated cell sorting (FACS) can be used to enrich for specific
      cell populations. This protocol provides a straightforward, standard approach for
      translational studies with highly complex, varied human specimens. 

PMID- 25590414
TI  - Conductance switching and organization of two structurally related molecular
      wires on gold.
AB  - The self-assembly and electron transfer properties of adsorbed organic molecules
      are of interest for the construction of miniaturized molecular circuitries. We
      have investigated with scanning probe microscopy the self-organization of two
      structurally related molecular wires embedded within a supportive alkanethiol
      matrix. Our results evidence heterogeneous adsorption patterns of the molecular
      wires on gold with either incommensurate unit cells driven into assembly by
      lateral interactions or a dynamic, commensurate distribution on gold, along with
      formation of distinct 2D phases. We also observed diffusion-based conductance
      switching for one of the molecular wires, due to its propensity toward weaker
      lateral interactions and Au-S adatom formation. We have further demonstrated
      through the use of scanning tunneling spectroscopy differential current-voltage
      response for each molecular wire, despite their close structural similarity. Such
      molecular wires embedded in alkanethiol matrix and exhibiting conductance
      switching phenomena have the potential to be used for the functionalization of
      electrodes in bioelectronic devices. 

PMID- 25590413
TI  - Wnt pathway activation and ABCB1 expression account for attenuation of proteasome
      inhibitor-mediated apoptosis in multidrug-resistant cancer cells.
AB  - Multiple drug resistance (MDR) is a major obstacle to attenuating the
      effectiveness of chemotherapy to many human malignancies. Proteasome inhibition
      induces apoptosis in a variety of cancer cells and is recognized as a novel
      anticancer therapy approach. Despite its success, some multiple myeloma patients
      are resistant or become refractory to ongoing treatment by bortezomib suggesting
      that chemoresistant cancer cells may have developed a novel mechanism directed
      against the proteasome inhibitor. The present study aimed to investigate
      potential mechanism(s) of attenuation in a MDR cell line, MES-SA/Dx5. We found
      that compared to the parental human uterus sarcoma cell line MES-SA cells, MES
      SA/Dx5 cells highly expressed the ABCB1 was more resistant to MG132 and
      bortezomib, escaping the proteasome inhibitor-induced apoptosis pathway. The
      resistance was reversed by co-treatment of MG132 and the ABCB1 inhibitor
      verapamil. The data indicated that ABCB1 might play a role in the efflux of MG132
      from the MES-SA/Dx5 cells to reduce MG132-induced apoptosis. Furthermore, the
      canonical Wnt pathway was found activated only in the MES-SA/Dx5 cells through
      active beta-catenin and related transactivation activities. Western blot analysis
      demonstrated that Wnt-targeting genes, including c-Myc and cyclin D1, were
      upregulated and were relevant in inhibiting the expression of p21 in MES-SA/Dx5
      cells. On the other hand, MES-SA cells expressed high levels of p21 and
      downregulated cyclin D1 and caused cell cycle arrest. Together, our study
      demonstrated the existence and participation of ABCB1 and the Wnt pathway in an
      MDR cell line that attenuated proteasome inhibitor-induced apoptosis.

PMID- 25590415
TI  - Cannabinoid receptors in mantle cell lymphoma.

PMID- 25590416
TI  - Phenotyping mouse pulmonary function in vivo with the lung diffusing capacity.
AB  - The mouse is now the primary animal used to model a variety of lung diseases. To
      study the mechanisms that underlie such pathologies, phenotypic methods are
      needed that can quantify the pathologic changes. Furthermore, to provide
      translational relevance to the mouse models, such measurements should be tests
      that can easily be done in both humans and mice. Unfortunately, in the present
      literature few phenotypic measurements of lung function have direct application
      to humans. One exception is the diffusing capacity for carbon monoxide, which is
      a measurement that is routinely done in humans. In the present report, we
      describe a means to quickly and simply measure this diffusing capacity in mice.
      The procedure involves brief lung inflation with tracer gases in an anesthetized
      mouse, followed by a 1 min gas analysis time. We have tested the ability of this
      method to detect several lung pathologies, including emphysema, fibrosis, acute
      lung injury, and influenza and fungal lung infections, as well as monitoring lung
      maturation in young pups. Results show significant decreases in all the lung
      pathologies, as well as an increase in the diffusing capacity with lung
      maturation. This measurement of lung diffusing capacity thus provides a pulmonary
      function test that has broad application with its ability to detect phenotypic
      structural changes with most of the existing pathologic lung models. 

PMID- 25590417
TI  - An accurate and portable eye movement detector for studying sleep in small
      animals.
AB  - Although eye movements are a highly valuable variable in attempts to precisely
      identify different periods of the sleep-wake cycle, their indirect measurement by
      electrooculography is not good enough. The present article describes an accurate
      and portable scleral search coil that allows the detection of tonic and phasic
      characteristics of eye movements in free-moving animals. Six adult Wistar rats
      were prepared for chronic recording of electroencephalography, electromyography
      and eye movements using the scleral search coil technique. We developed a
      miniature magnetic field generator made with two coils, consisting of 35 turns
      and 15 mm diameter of insulated 0.2 mm cooper wire, mounted in a frame of carbon
      fibre. This portable scleral search coil was fixed on the head of the animal,
      with each magnetic coil parallel to the eye coil and at 5 mm from each eye. Eye
      movements detected by the portable scleral search coil were compared with those
      measured by a commercial scleral search coil requiring immobilizing the head of
      the animal. No qualitative differences were found between the two scleral search
      coil systems in their capabilities to detect eye movements. This innovative
      portable scleral search coil system is an essential tool to detect slow changes
      in eye position and miniature rapid eye movements during sleep. The portable
      scleral search coil is much more suitable for detecting eye movements than any
      previously available system because of its precision and simplicity, and because
      it does not require immobilization of the animal's head. 

PMID- 25590419
TI  - Catalytic kinetics of single gold nanoparticles observed via optical microwell
      arrays.
AB  - Catalytic activities and kinetics are measured at the single-particle level for
      gold nanoparticles catalyzing a fluorogenic oxidation reaction. This measurement
      is accomplished by confining the reactions in optically addressable microwell
      arrays. Citrate-capped gold nanoparticles are isolated in sealed ~70 fL
      microwells along with a substrate, and the accumulation of a fluorescent product
      over time is observed. Thousands of reactions are measured in parallel. Catalytic
      activities are calculated for each nanoparticle and the activity distribution is
      analyzed. 

PMID- 25590418
TI  - In vitro aggregation assays using hyperphosphorylated tau protein.
AB  - Alzheimer's disease is one of a large group of neurodegenerative disorders known
      as tauopathies that are manifested by the neuronal deposits of
      hyperphosphorylated tau protein in the form of neurofibrillary tangles (NFTs).
      The density of NFT correlates well with cognitive impairment and other
      neurodegenerative symptoms, thus prompting the endeavor of developing tau
      aggregation-based therapeutics. Thus far, however, tau aggregation assays use
      recombinant or synthetic tau that is devoid of the pathology-related
      phosphorylation marks. Here we describe two assays using recombinant,
      hyperphosphorylated tau as the subject. These assays can be scaled up for high
      throughput screens for compounds that can modulate the kinetics or stability of
      hyperphosphorylated tau aggregates. Novel therapeutics for Alzheimer's disease
      and other tauopathies can potentially be discovered using hyperphosphorylated tau
      isoforms. 

PMID- 25590420
TI  - Cadmium toxicity to Microcystis aeruginosa PCC 7806 and its microcystin-lacking
      mutant.
AB  - The adverse effects of microcystin (MC) produced by cyanobacteria have drawn
      considerable attention from the public. Yet it remains unclear whether MC confers
      any benefits to the cyanobacteria themselves. One suggested function of MC is
      complexation, which may influence the bioaccumulation and toxicity of trace
      metals. To test this hypothesis, we examined Cd toxicity to wild-type Microcystis
      aeruginosa PCC 7806 (WT) and its MC-lacking mutant (MT) under nutrient-enriched
      (+NP), phosphorus-limited (-P), and nitrogen-limited (-N) conditions. The
      accumulation of Cd and the biochemical parameters associated with its
      detoxification [total phosphorus (TP), inorganic polyphosphate (Poly-P), and
      glutathione (GSH) in the cells as well as intra- and extra-cellular
      carbohydrates] were quantified. Although the -P cyanobacteria accumulated less Cd
      than their +NP and -N counterparts, the different nutrient-conditioned
      cyanobacteria were similarly inhibited by similar free ion concentration of Cd in
      the medium ([Cd2+]F). Such good toxicity predictability of [Cd2+]F was ascribed
      to the synchronous decrease in the intracellular concentrations of Cd and TP.
      Nevertheless, Cd toxicity was still determined by the intracellular Cd to
      phosphorus ratio (Cd/P), in accordance with what has been reported in the
      literature. On the other hand, the concentrations of TP, Poly-P, and
      carbohydrates went up, but GSH concentration dropped down with the enhancement of
      [Cd2+]F, indicating their association with Cd detoxification. Although the
      inactivation of MC peptide synthetase gene had some nutrient and Cd concentration
      dependent effects on the parameters above, both cyanobacterial strains showed the
      same Cd accumulation ability and displayed similar Cd sensitivity. These results
      suggest that MC cannot affect metal toxicity either by regulating metal
      accumulation or by altering the detoxification ability of the cyanobacteria.
      Other possible functions of MC need to be further investigated. 

PMID- 25590421
TI  - Biohydrogen production from food waste hydrolysate using continuous mixed
      immobilized sludge reactors.
AB  - A continuous mixed immobilized sludge reactor (CMISR) using activated carbon as
      support carrier for dark fermentative hydrogen production from enzymatic
      hydrolyzed food waste was developed. The effects of immobilized sludge packing
      ratio (10-20%, v/v) and substrate loading rate (OLR) (8-40kg/m(3)/d) on
      biohydrogen production were examined, respectively. The hydrogen production rates
      (HPRs) with packing ratio of 15% were significantly higher than the results
      obtained from packing ratio of 10% and 20%. The best HPR of 353.9ml/h/L was
      obtained at the condition of packing ratio=15% and OLR=40kg/m(3)/d. The Minitab
      was used to elicit the effects of OLR and packing ratio on HPR (Y) which could be
      expressed as Y=5.31 OLR+296 packing ratio+40.3 (p=0.003). However, the highest
      hydrogen yield (85.6ml/g food waste) was happened at OLR of 16kg/m(3)/d because
      of H2 partial pressure and oxidization/reduction of NADH. 

PMID- 25590422
TI  - Sufficient utilization of natural fluctuating light intensity is an effective
      approach of promoting lipid productivity in oleaginous microalgal cultivation
      outdoors.
AB  - The effects of fluctuating intensity of solar radiation on biomass and lipid in
      oleaginous microalgae are important. However, this topic has not been the subject
      of studies for a long time. In this study, four oleaginous microalgae from semi
      arid areas were screened and cultivated outdoors under different fluctuating
      intensities. Results showed that the highest lipid productivities and neutral
      lipid (NL) contents occurred under high fluctuating intensity (HFI), in which 13
      20% of the increased NL came from glycolipid transformation without phospholipid
      conversion. Chlorella sp. L1 and Monoraphidium dybowskii Y2 obtained from
      biological soil crusts in desert had the largest biomass (137.13, 106.61mgL(-1)d(
      1)) and lipid yields (35.06, 32.45mgL(-1)d(-1)) under HFI. The highest areal
      lipid productivities of 9.06 and 8.95gm(-2)d(-1) and better biodiesel quality
      were observed under HFI. Accordingly, sufficiently adopting fluctuating light
      intensity outdoors to culture microalgae was an economic and effective approach. 

PMID- 25590423
TI  - A kinetic study on microwave-assisted conversion of cellulose and lignocellulosic
      waste into hydroxymethylfurfural/furfural.
AB  - Native cellulose, lignocellulosic materials from Brazil (carnauba palm leaves and
      macauba pulp and shell) and pine nut shell from Spain have been studied as
      substrates for the production of HMF and furfural in a conventional microwave
      oven. In order to promote the dissolution of native cellulose, several ionic
      liquids, catalysts, organic solvents and water doses have been assessed. The most
      suitable mixture (5mL of choline chloride/oxalic acid, 2mL of sulfolane, 2mL of
      water, 0.02g of TiO2 and 0.1g of substrate) has been chosen to conduct kinetic
      studies at different reaction times (5-60min) and various temperatures (120-200
      degrees C) and to evaluate the best conditions for HMF+furfural production
      according to Seaman's model. The best production yields of HMF+furfural have been
      attained for native cellulose, with a yield of 53.24% when an ultrasonic
      pretreatment was used prior to a microwave treatment with stirring. 

PMID- 25590424
TI  - Improving performance of microbial fuel cell while controlling methanogenesis by
      Chaetoceros pretreatment of anodic inoculum.
AB  - Loss of substrate due to methanogenesis reduces Coulombic efficiency (CE) of the
      microbial fuel cell (MFC) significantly. Hexadecatrienoic acid present in the
      marine algae Chaetoceros inhibits the growth of methanogenic archaea. Influence
      of Chaetoceros pre-treated mixed anaerobic sludge on the electrogenic activity of
      MFC was evaluated. A MFC inoculated with Chaetoceros pre-treated mixed anaerobic
      sludge demonstrated maximum CE of 45.18%, with volumetric power density of
      21.43W/m(3) and current density of 93A/m(3). Cyclic voltammetry indicated higher
      electron discharge on the anode surface due to suppression of methanogenesis.
      Tafel analysis also showed a higher exchange current density and a lower Tafel
      slope and charge transfer resistance, indicating advantage of this pre-treatment
      method in reducing the cell internal losses. A 60% reduction in specific
      methanogenic activity was observed in anaerobic sludge pre-treated with
      Chaetoceros; emphasizing significance of this pretreatment for suppressing
      methanogenesis and its utility for enhancing electricity generation in MFC. 

PMID- 25590425
TI  - Scaling-up of membraneless microbial electrolysis cells (MECs) for domestic
      wastewater treatment: Bottlenecks and limitations.
AB  - Microbial electrolysis cells (MECs) have the potential to become a sustainable
      domestic wastewater (dWW) treatment system. However, new scale-up experiences are
      required to gain knowledge of critical issues in MEC designs. In this study we
      assess the ability of two twin membraneless MEC units (that are part of a modular
      pilot-scale MEC) to treat dWW. Batch tests yielded COD removal efficiencies as
      high as 92%, with most of the hydrogen (>80% of the total production) being
      produced during the first 48h. During the continuous tests, MECs performance
      deteriorated significantly (energy consumption was relatively high and COD
      removal efficiencies fell below 10% in many cases), which was attributed to an
      inadequate configuration of the anodic chamber, insufficient mixing inside this
      chamber, inefficient hydrogen management on the cathode side and finally to dWW
      in itself. Some alternatives to the current design are suggested. 

PMID- 25590426
TI  - Production of fermentable sugars from sugarcane bagasse by enzymatic hydrolysis
      after autohydrolysis and mechanical refining.
AB  - The autohydrolysis process has been considered a simple, low-cost and
      environmental friendly technology for generation of sugars from biomass. In order
      to improve accessibility of enzymes during enzymatic hydrolysis as well as to
      allow the recovery of hemicellulose in the filtrate, the sugarcane bagasse was
      pretreated using autohydrolysis followed by a mechanical refining process. The
      autohydrolysis was carried out in three different conditions. Autohydrolysis at
      190 degrees C for 10min provided the highest overall sugar (19.2/100g raw
      bagasse) in prehydrolyzate. The enzymatic hydrolysis step was performed for all
      the post-treated solids with and without refining at enzyme loadings of 5 and
      10FPU/g for 96h. A total of 84.4% of sugar can be recovered from sugarcane
      bagasse at 180 degrees C for 20min with 5 FPU/g enzyme charge. The economic
      analysis for the proposed method showed that the bioethanol production can have a
      financial return larger than 12%. 

PMID- 25590427
TI  - Synaptic plasticity enables adaptive self-tuning critical networks.
AB  - During rest, the mammalian cortex displays spontaneous neural activity. Spiking
      of single neurons during rest has been described as irregular and asynchronous.
      In contrast, recent in vivo and in vitro population measures of spontaneous
      activity, using the LFP, EEG, MEG or fMRI suggest that the default state of the
      cortex is critical, manifested by spontaneous, scale-invariant, cascades of
      activity known as neuronal avalanches. Criticality keeps a network poised for
      optimal information processing, but this view seems to be difficult to reconcile
      with apparently irregular single neuron spiking. Here, we simulate a 10,000
      neuron, deterministic, plastic network of spiking neurons. We show that a
      combination of short- and long-term synaptic plasticity enables these networks to
      exhibit criticality in the face of intrinsic, i.e. self-sustained, asynchronous
      spiking. Brief external perturbations lead to adaptive, long-term modification of
      intrinsic network connectivity through long-term excitatory plasticity, whereas
      long-term inhibitory plasticity enables rapid self-tuning of the network back to
      a critical state. The critical state is characterized by a branching parameter
      oscillating around unity, a critical exponent close to -3/2 and a long tail
      distribution of a self-similarity parameter between 0.5 and 1. 

PMID- 25590428
TI  - Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the
      dynamics of epigenetic modifications from stem cells to differentiated cells.
AB  - The intestinal epithelium is a particularly attractive biological adult model to
      study epigenetic mechanisms driving adult stem cell renewal and cell
      differentiation. Since epigenetic modifications are dynamic, we have developed an
      original ex vivo approach to study the expression and epigenetic profiles of key
      genes associated with either intestinal cell pluripotency or differentiation by
      isolating cryosections of the intestinal crypt-villus axis. Gene expression, DNA
      methylation and histone modifications were studied by qRT-PCR, methylation
      specific PCR and micro-chromatin immunoprecipitation, respectively. Using this
      approach, it was possible to identify segment-specific methylation and chromatin
      profiles. We show that (i) expression of intestinal stem cell markers (Lgr5,
      Ascl2) exclusively in the crypt is associated with active histone marks, (ii)
      promoters of all pluripotency genes studied and transcription factors involved in
      intestinal cell fate (Cdx2) harbour a bivalent chromatin pattern in the crypts
      and (iii) expression of differentiation markers (Muc2, Sox9) along the crypt
      villus axis is associated with DNA methylation. Hence, using an original model of
      cryosectioning along the crypt-villus axis that allows in situ detection of
      dynamic epigenetic modifications, we demonstrate that regulation of pluripotency
      and differentiation markers in healthy intestinal mucosa involves different and
      specific epigenetic mechanisms. 

PMID- 25590429
TI  - Preparation and friction force microscopy measurements of immiscible, opposing
      polymer brushes.
AB  - Solvated polymer brushes are well known to lubricate high-pressure contacts,
      because they can sustain a positive normal load while maintaining low friction at
      the interface. Nevertheless, these systems can be sensitive to wear due to
      interdigitation of the opposing brushes. In a recent publication, we have shown
      via molecular dynamics simulations and atomic force microscopy experiments, that
      using an immiscible polymer brush system terminating the substrate and the slider
      surfaces, respectively, can eliminate such interdigitation. As a consequence,
      wear in the contacts is reduced. Moreover, the friction force is two orders of
      magnitude lower compared to traditional miscible polymer brush systems. This
      newly proposed system therefore holds great potential for application in
      industry. Here, the methodology to construct an immiscible polymer brush system
      of two different brushes each solvated by their own preferred solvent is
      presented. The procedure how to graft poly(N-isopropylacrylamide) (PNIPAM) from a
      flat surface and poly(methyl methacrylate) (PMMA) from an atomic force microscopy
      (AFM) colloidal probe is described. PNIPAM is solvated in water and PMMA in
      acetophenone. Via friction force AFM measurements, it is shown that the friction
      for this system is indeed reduced by two orders of magnitude compared to the
      miscible system of PMMA on PMMA solvated in acetophenone. 

PMID- 25590431
TI  - Poly(vinyl alcohol)/gelatin Hydrogels Cultured with HepG2 Cells as a 3D Model of
      Hepatocellular Carcinoma: A Morphological Study.
AB  - It has been demonstrated that three-dimensional (3D) cell culture models
      represent fundamental tools for the comprehension of cellular phenomena both for
      normal and cancerous tissues. Indeed, the microenvironment affects the cellular
      behavior as well as the response to drugs. In this study, we performed a
      morphological analysis on a hepatocarcinoma cell line, HepG2, grown for 24 days
      inside a bioartificial hydrogel composed of poly(vinyl alcohol) (PVA) and gelatin
      (G) to model a hepatocellular carcinoma (HCC) in 3D. Morphological features of
      PVA/G hydrogels were investigated, resulting to mimic the trabecular structure of
      liver parenchyma. A histologic analysis comparing the 3D models with HepG2 cell
      monolayers and tumor specimens was performed. In the 3D setting, HepG2 cells were
      viable and formed large cellular aggregates showing different morphotypes with
      zonal distribution. Furthermore, beta-actin and alpha5beta1 integrin revealed a
      morphotype-related expression; in particular, the frontline cells were
      characterized by a strong immunopositivity on a side border of their membrane,
      thus suggesting the formation of lamellipodia-like structures apt for migration.
      Based on these results, we propose PVA/G hydrogels as valuable substrates to
      develop a long term 3D HCC model that can be used to investigate important
      aspects of tumor biology related to migration phenomena. 

PMID- 25590433
TI  - Green approach for photocatalytic Cu(II)-EDTA degradation over TiO2: toward
      environmental sustainability.
AB  - A green approach was successfully developed to reap three environmental benefits
      simultaneously: (1) clean water production, (2) hydrogen (H2) generation, and (3)
      well-dispersed in situ Cu(2+) recovery for direct TiO2-CuO composite reclamation,
      by exploiting the synergistic integration of photocatalytic reaction of Cu-EDTA
      and one-dimensional (1D) ultralong and ultrathin TiO2 nanofibers. In this light
      initiated system, Cu-EDTA was oxidized by TiO2 thus releasing Cu(2+) which was
      reduced and recovered through uniform adsorption onto the long and porous TiO2
      surface. A win-win platform was thus attained, on which Cu was recovered while
      providing active sites for H2 generation via photoreduction of H2O and enhancing
      photo-oxidation of remaining intermediate oxidation byproducts. Experimental
      results showed a H2 generation rate of 251 MUmol/h concomitantly with TOC
      reduction. The used TiO2 nanofibers deposited with Cu were reclaimed directly as
      the TiO2-CuO composite after a facile heat treatment without additional chemicals
      and subsequently reusable for photocatalytic treatment of other wastewater
      (glycerol) to cogenerate H2 and clean water under both UV-visible and visible
      light. This study expounds a significant advancement through an ingenious
      integration which enhances the environmental sustainability of Cu-EDTA treatment
      via TiO2 photocatalysis. It also represents a promising and adoptable approach to
      synthesize other functional composite nanomaterials in a green manner thus
      broadening its environmental application spectrum, as it promotes industrial
      environmental management via waste segregation and motivates research to recover
      more resources from wastewater. 

PMID- 25590430
TI  - Bacterial flagella: twist and stick, or dodge across the kingdoms.
AB  - The flagellum organelle is an intricate multiprotein assembly best known for its
      rotational propulsion of bacteria. However, recent studies have expanded our
      knowledge of other functions in pathogenic contexts, particularly adherence and
      immune modulation, e.g., for Salmonella enterica, Campylobacter jejuni,
      Pseudomonas aeruginosa, and Escherichia coli. Flagella-mediated adherence is
      important in host colonisation for several plant and animal pathogens, but the
      specific interactions that promote flagella binding to such diverse host tissues
      has remained elusive. Recent work has shown that the organelles act like probes
      that find favourable surface topologies to initiate binding. An emerging theme is
      that more general properties, such as ionic charge of repetitive binding epitopes
      and rotational force, allow interactions with plasma membrane components. At the
      same time, flagellin monomers are important inducers of plant and animal innate
      immunity: variation in their recognition impacts the course and outcome of
      infections in hosts from both kingdoms. Bacteria have evolved different
      strategies to evade or even promote this specific recognition, with some
      important differences shown for phytopathogens. These studies have provided a
      wider appreciation of the functions of bacterial flagella in the context of both
      plant and animal reservoirs. 

PMID- 25590432
TI  - The human otubain2-ubiquitin structure provides insights into the cleavage
      specificity of poly-ubiquitin-linkages.
AB  - Ovarian tumor domain containing proteases cleave ubiquitin (Ub) and ubiquitin
      like polypeptides from proteins. Here we report the crystal structure of human
      otubain 2 (OTUB2) in complex with a ubiquitin-based covalent inhibitor, Ub-Br2.
      The ubiquitin binding mode is oriented differently to how viral otubains (vOTUs)
      bind ubiquitin/ISG15, and more similar to yeast and mammalian OTUs. In contrast
      to OTUB1 which has exclusive specificity towards Lys48 poly-ubiquitin chains,
      OTUB2 cleaves different poly-Ub linked chains. N-terminal tail swapping
      experiments between OTUB1 and OTUB2 revealed how the N-terminal structural motifs
      in OTUB1 contribute to modulating enzyme activity and Ub-chain selectivity, a
      trait not observed in OTUB2, supporting the notion that OTUB2 may affect a
      different spectrum of substrates in Ub-dependent pathways. 

PMID- 25590434
TI  - Superhydrophobic cuprous oxide nanostructures on phosphor-copper meshes and their
      oil-water separation and oil spill cleanup.
AB  - A simple aqueous solution-immersion process was established to fabricate highly
      dense ordered Cu2O nanorods on commercial phosphor-copper mesh, with which the
      preparation was accomplished in distilled water. The present method, with the
      advantages of simple operation, low cost, short reaction time, and environmental
      friendliness, can be well adopted to fabricate desired Cu2O nanostructures on the
      phosphor-copper mesh under mild conditions. After surface modification with 1
      dodecanethiol, the Cu2O nanostructure obtained on the phosphor-copper mesh
      exhibits excellent superhydrophobicity and superoleophilicity. Besides, a "mini
      boat" made from the as-prepared superhydrophobic phosphor-copper mesh can float
      freely on water surface and in situ collect oil from water surface. This
      demonstrates that the present approach, being facile, inexpensive, and
      environmentally friendly, could find promising application in oil-water
      separation and off shore oil spill cleanup. 

PMID- 25590436
TI  - Comparison of nephrotoxicity associated to different lipid formulations of
      amphotericin B: a real-life study.
AB  - Amphotericin B (AmB) use is limited by the occurrence of kidney toxicity. Here,
      we evaluated the incidence and impact of nephrotoxicity in a large series of
      patients receiving therapy with amphotericin B deoxycholate (d-AmB), liposomal
      AmB (L-AmB), or AmB lipid complex (ABLC), in a clinical practice scenario. In a
      retrospective cohort study, patients treated with different AmB formulations
      between 2003 and 2012 were evaluated. Medical records and laboratory data were
      reviewed. Nephrotoxicity was determined according to modified RIFLE criteria.
      Predictors of nephrotoxicity and mortality were determined and treatment groups
      were compared. About 431 patients were studied (d-AmB, n = 236; L-AmB, n = 105;
      ABLC, n = 90). Frequency of severe nephrotoxicity (RIFLE 'Failure') was 11.5%,
      2.4% and 7.2% for d-AmB, L-AmB and ABLC, respectively (P = 0.046). Use of L-AmB
      was found to be an independent protective factor (OR: 0.18; 95% CI: 0.03-0.64; P
      = 0.006) for severe nephrotoxicity, considering d-AmB as a reference. L-AmB was
      also a protective factor for mortality (OR: 0.56; 95% CI: 0.32-0.99; P = 0.046).
      In addition, in-hospital overall mortality was associated with cancer, previous
      dialysis, evolution to dialysis, and stay in the intensive care unit. Patients
      treated with ABLC showed similar frequency of severe kidney toxicity than those
      treated with d-AmB. L-AmB was associated with better outcomes than other
      formulations, including severe nephrotoxicity and overall mortality. 

PMID- 25590438
TI  - Anomalous rapid defect annihilation in self-assembled nanopatterns by defect
      melting.
AB  - Molecular self-assembly commonly suffers from dense structural defect formation.
      Spontaneous defect annihilation in block copolymer (BCP) self-assembly is
      particularly retarded due to significant energy barrier for polymer chain
      diffusion and structural reorganization. Here we present localized defect melting
      induced by blending short neutral random copolymer chain as an unusual method to
      promote the defect annihilation in BCP self-assembled nanopatterns. Chemically
      neutral short random copolymer chains blended with BCPs are specifically
      localized and induce local disordered states at structural defect sites in the
      self-assembled nanopatterns. Such localized "defect melting" relieves the energy
      penalty for polymer diffusion and morphology reorganization such that spontaneous
      defect annihilation by mutual coupling is anomalously accelerated upon thermal
      annealing. Interestingly, neutral random copolymer chain blending also causes
      morphology-healing self-assembly behavior that can generate large-area highly
      ordered 10 nm scale nanopattern even upon poorly defined defective prepatterns.
      Underlying mechanisms of the unusual experimental findings are thoroughly
      investigated by three-dimensional self-consistent field theory calculation. 

PMID- 25590435
TI  - Bartonella spp. bacteremia in blood donors from Campinas, Brazil.
AB  - Bartonella species are blood-borne, re-emerging organisms, capable of causing
      prolonged infection with diverse disease manifestations, from asymptomatic
      bacteremia to chronic debilitating disease and death. This pathogen can survive
      for over a month in stored blood. However, its prevalence among blood donors is
      unknown, and screening of blood supplies for this pathogen is not routinely
      performed. We investigated Bartonella spp. prevalence in 500 blood donors from
      Campinas, Brazil, based on a cross-sectional design. Blood samples were
      inoculated into an enrichment liquid growth medium and sub-inoculated onto blood
      agar. Liquid culture samples and Gram-negative isolates were tested using a genus
      specific ITS PCR with amplicons sequenced for species identification. Bartonella
      henselae and Bartonella quintana antibodies were assayed by indirect
      immunofluorescence. B. henselae was isolated from six donors (1.2%). Sixteen
      donors (3.2%) were Bartonella-PCR positive after culture in liquid or on solid
      media, with 15 donors infected with B. henselae and one donor infected with
      Bartonella clarridgeiae. Antibodies against B. henselae or B. quintana were found
      in 16% and 32% of 500 blood donors, respectively. Serology was not associated
      with infection, with only three of 16 Bartonella-infected subjects seropositive
      for B. henselae or B. quintana. Bartonella DNA was present in the bloodstream of
      approximately one out of 30 donors from a major blood bank in South America.
      Negative serology does not rule out Bartonella spp. infection in healthy
      subjects. Using a combination of liquid and solid cultures, PCR, and DNA
      sequencing, this study documents for the first time that Bartonella spp.
      bacteremia occurs in asymptomatic blood donors. Our findings support further
      evaluation of Bartonella spp. transmission which can occur through blood
      transfusions. 

PMID- 25590437
TI  - S-phase-dependent p50/NF-kB1 phosphorylation in response to ATR and replication
      stress acts to maintain genomic stability.
AB  - The apical damage kinase, ATR, is activated by replication stress (RS) both in
      response to DNA damage and during normal S-phase. Loss of function studies
      indicates that ATR acts to stabilize replication forks, block cell cycle
      progression and promote replication restart. Although checkpoint failure and
      replication fork collapse can result in cell death, no direct cytotoxic pathway
      downstream of ATR has previously been described. Here, we show that ATR directly
      reduces survival by inducing phosphorylation of the p50 (NF-kappaB1, p105)
      subunit of NF-kB and moreover, that this response is necessary for genome
      maintenance independent of checkpoint activity. Cell free and in vivo studies
      demonstrate that RS induces phosphorylation of p50 in an ATR-dependent but DNA
      damage-independent manner that acts to modulate NF-kB activity without affecting
      p50/p65 nuclear translocation. This response, evident in human and murine cells,
      occurs not only in response to exogenous RS but also during the unperturbed S
      phase. Functionally, the p50 response results in inhibition of anti-apoptotic
      gene expression that acts to sensitize cells to DNA strand breaks independent of
      damage repair. Ultimately, loss of this pathway causes genomic instability due to
      the accumulation of chromosomal breaks. Together, the data indicate that during S
      phase ATR acts via p50 to ensure that cells with elevated levels of replication
      associated DNA damage are eliminated. 

PMID- 25590439
TI  - PCTAIRE1/PCTK1/CDK16: a new oncotarget?

PMID- 25590440
TI  - Tutorial for writing systematic reviews for the Brazilian Journal of Physical
      Therapy (BJPT).
AB  - Systematic reviews aim to summarize all evidence using very rigorous methods in
      order to address a specific research question with less bias as possible.
      Systematic reviews are widely used in the field of physical therapy, however not
      all reviews have good quality. This tutorial aims to guide authors of the
      Brazilian Journal of Physical Therapy on how systematic reviews should be
      conducted and reported in order to be accepted for publication. It is expected
      that this tutorial will help authors of systematic reviews as well as journal
      editors and reviewers on how to conduct, report, critically appraise and
      interpret this type of study design.

PMID- 25590441
TI  - Static body postural misalignment in individuals with temporomandibular
      disorders: a systematic review.
AB  - BACKGROUND: The association between body postural changes and temporomandibular
      disorders (TMD) has been widely discussed in the literature, however, there is
      little evidence to support this association. OBJECTIVES: The aim of the present
      study was to conduct a systematic review to assess the evidence concerning the
      association between static body postural misalignment and TMD. METHOD: A search
      was conducted in the PubMed/Medline, Embase, Lilacs, Scielo, Cochrane, and Scopus
      databases including studies published in English between 1950 and March 2012.
      Cross-sectional, cohort, case control, and survey studies that assessed body
      posture in TMD patients were selected. Two reviewers performed each step
      independently. A methodological checklist was used to evaluate the quality of the
      selected articles. RESULTS: Twenty studies were analyzed for their methodological
      quality. Only one study was classified as a moderate quality study and two were
      classified as strong quality studies. Among all studies considered, only 12
      included craniocervical postural assessment, 2 included assessment of
      craniocervical and shoulder postures,, and 6 included global assessment of body
      posture. CONCLUSION: There is strong evidence of craniocervical postural changes
      in myogenous TMD, moderate evidence of cervical postural misalignment in
      arthrogenous TMD, and no evidence of absence of craniocervical postural
      misalignment in mixed TMD patients or of global body postural misalignment in
      patients with TMD. It is important to note the poor methodological quality of the
      studies, particularly those regarding global body postural misalignment in TMD
      patients.

PMID- 25590442
TI  - Walking training associated with virtual reality-based training increases walking
      speed of individuals with chronic stroke: systematic review with meta-analysis.
AB  - OBJECTIVE: To systematically review the available evidence on the efficacy of
      walking training associated with virtual reality-based training in patients with
      stroke. The specific questions were: Is walking training associated with virtual
      reality-based training effective in increasing walking speed after stroke? Is
      this type of intervention more effective in increasing walking speed, than non
      virtual reality-based walking interventions? METHOD: A systematic review with
      meta-analysis of randomized clinical trials was conducted. Participants were
      adults with chronic stroke and the experimental intervention was walking training
      associated with virtual reality-based training to increase walking speed. The
      outcome data regarding walking speed were extracted from the eligible trials and
      were combined using a meta-analysis approach. RESULTS: Seven trials representing
      eight comparisons were included in this systematic review. Overall, the virtual
      reality-based training increased walking speed by 0.17 m/s (IC 95% 0.08 to 0.26),
      compared with placebo/nothing or non-walking interventions. In addition, the
      virtual reality-based training increased walking speed by 0.15 m/s (IC 95% 0.05
      to 0.24), compared with non-virtual reality walking interventions. CONCLUSIONS:
      This review provided evidence that walking training associated with virtual
      reality-based training was effective in increasing walking speed after stroke,
      and resulted in better results than non-virtual reality interventions.

PMID- 25590443
TI  - Relationship between the climbing up and climbing down stairs domain scores on
      the FES-DMD, the score on the Vignos Scale, age and timed performance of
      functional activities in boys with Duchenne muscular dystrophy.
AB  - BACKGROUND: Knowing the potential for and limitations of information generated
      using different evaluation instruments favors the development of more accurate
      functional diagnoses and therapeutic decision-making. OBJECTIVE: To investigate
      the relationship between the number of compensatory movements when climbing up
      and going down stairs, age, functional classification and time taken to perform a
      tested activity (TA) of going up and down stairs in boys with Duchenne muscular
      dystrophy (DMD). METHOD: A bank of movies featuring 30 boys with DMD performing
      functional activities was evaluated. Compensatory movements were assessed using
      the climbing up and going down stairs domain of the Functional Evaluation Scale
      for Duchenne Muscular Dystrophy (FES-DMD); age in years; functional
      classification using the Vignos Scale (VS), and TA using a timer. Statistical
      analyses were performed using the Spearman correlation test. RESULTS: There is a
      moderate relationship between the climbing up stairs domain of the FES-DMD and
      age (r=0.53, p=0.004) and strong relationships with VS (r=0.72, p=0.001) and TA
      for this task (r=0.83, p<0.001). There were weak relationships between the going
      down stairs domain of the FES-DMD-going down stairs with age (r=0.40, p=0.032),
      VS (r=0.65, p=0.002) and TA for this task (r=0.40, p=0.034). CONCLUSION: These
      findings indicate that the evaluation of compensatory movements used when
      climbing up stairs can provide more relevant information about the evolution of
      the disease, although the activity of going down stairs should be investigated,
      with the aim of enriching guidance and strengthening accident prevention. Data
      from the FES-DMD, age, VS and TA can be used in a complementary way to formulate
      functional diagnoses. Longitudinal studies and with broader age groups may
      supplement this information.

PMID- 25590444
TI  - Muscular performance characterization in athletes: a new perspective on
      isokinetic variables.
AB  - BACKGROUND: Isokinetic dynamometry allows the measurement of several variables
      related to muscular performance, many of which are seldom used, while others are
      redundantly applied to the characterization of muscle function. OBJECTIVES: The
      present study aimed to establish the particular features of muscle function that
      are captured by the variables currently included in isokinetic assessment and to
      determine which variables best represent these features in order to achieve a
      more objective interpretation of muscular performance. METHOD: This study
      included 235 male athletes. They performed isokinetic tests of concentric knee
      flexion and extension of the dominant leg at a velocity of 60o/s. An exploratory
      factor analysis was performed. RESULTS: The findings demonstrated that isokinetic
      variables can characterize more than muscle torque production and pointed to the
      presence of 5 factors that enabled the characterization of muscular performance
      according to 5 different domains or constructs. CONCLUSIONS: The constructs can
      be described by torque generation capacity; variation of the torque generation
      capacity along repetitions; movement deceleration capacity;
      mechanical/physiological factors of torque generation; and acceleration capacity
      (torque development). Fewer than eight out of sixteen variables are enough to
      characterize these five constructs. Our results suggest that these variables and
      these 5 domains may lead to a more systematic and optimized interpretation of
      isokinetic assessments.

PMID- 25590445
TI  - Characteristics and associated factors with sports injuries among children and
      adolescents.
AB  - BACKGROUND: The participation of children and adolescents in sports is becoming
      increasingly common, and this increased involvement raises concerns about the
      occurrence of sports injuries. OBJECTIVES: To characterize the sports injuries
      and verify the associated factors with injuries in children and adolescents.
      METHOD: Retrospective, epidemiological study. One thousand three hundred and
      eleven children and adolescents up to 18 years of age enrolled in a sports
      initiation school in the city of Presidente Prudente, State of Sao Paulo, Brazil.
      A reported condition inquiry in interview form was used to obtain personal data
      and information on training and sports injuries in the last 12 months. Injury was
      considered any physical complaint resulting from training and/or competition that
      limited the participation of the individual for at least one day, regardless of
      the need for medical care. RESULTS: The injury rate per 1000 hours of exposure
      was 1.20 among the children and 1.30 among the adolescents. Age, anthropometric
      data, and training characteristics only differed with regard to the presence or
      absence of injuries among the adolescents. The most commonly reported
      characteristics involving injuries in both the children and adolescents were the
      lower limbs, training, non-contact mechanism, mild injury, asymptomatic return to
      activities, and absence of recurrence. CONCLUSIONS: The injury rate per 1000
      hours of exposure was similar among children and adolescents. Nevertheless, some
      peculiarities among adolescents were observed with greater values for weight,
      height, duration of training, and weekly hours of practice.

PMID- 25590446
TI  - Can the adapted arcometer be used to assess the vertebral column in children?
AB  - BACKGROUND: The adapted arcometer has been validated for use in adults. However,
      its suitability for use in children can be questioned given the structural
      differences present in these populations. OBJECTIVE: To verify the concurrent
      validity, repeatability, and intra- and inter-reproducibility of the adapted
      arcometer for the measurement of the angles of thoracic kyphosis and lumbar
      lordosis in children. METHOD: Forty children were evaluated using both sagittal
      radiography of the spine and the adapted arcometer. The evaluations using the
      arcometer were carried out by two trained evaluators on two different days. In
      the statistical treatment, the intraclass correlation coefficient (ICC),
      Pearson's product moment correlation, Spearman's rho, the paired t test, and
      Wilcoxon's test were used (alpha=.05). RESULTS: A moderate and significant
      correlation was found between the x-ray and the adapted arcometer regarding
      thoracic kyphosis, but no correlation was found regarding lumbar lordosis.
      Repeatability and intra-evaluator reproducibility of the thoracic kyphosis and
      lumbar lordosis were confirmed, which was not the case of inter-evaluator
      reproducibility. CONCLUSION: The adapted arcometer can be used to accompany
      postural alterations in children made by the same evaluator, while its use for
      diagnostic purposes and continued evaluation by different evaluators cannot be
      recommended. Further studies with the aim of adapting this instrument for use in
      children are recommended.

PMID- 25590447
TI  - Breathing exercises: influence on breathing patterns and thoracoabdominal motion
      in healthy subjects.
AB  - BACKGROUND: The mechanisms underlying breathing exercises have not been fully
      elucidated. OBJECTIVES: To evaluate the impact of four on breathing exercises
      (diaphragmatic breathing, inspiratory sighs, sustained maximal inspiration and
      intercostal exercise) the on breathing pattern and thoracoabdominal motion in
      healthy subjects. METHOD: Fifteen subjects of both sexes, aged 23 +/- 1.5 years
      old and with normal pulmonary function tests, participated in the study. The
      subjects were evaluated using the optoelectronic plethysmography system in a
      supine position with a trunk inclination of 45 degrees  during quiet breathing
      and the breathing exercises. The order of the breathing exercises was randomized.
      Statistical analysis was performed by the Friedman test and an ANOVA for repeated
      measures with one factor (breathing exercises), followed by preplanned contrasts
      and Bonferroni correction. A p<0.005 value was considered significant. RESULTS:
      All breathing exercises significantly increased the tidal volume of the chest
      wall (V(cw)) and reduced the respiratory rate (RR) in comparison to quiet
      breathing. The diaphragmatic breathing exercise was responsible for the lowest
      V(cw), the lowest contribution of the rib cage, and the highest contribution of
      the abdomen. The sustained maximal inspiration exercise promoted greater
      reduction in RR compared to the diaphragmatic and intercostal exercises.
      Inspiratory sighs and intercostal exercises were responsible for the highest
      values of minute ventilation. Thoracoabdominal asynchrony variables increased
      significantly during diaphragmatic breathing. CONCLUSIONS: The results showed
      that the breathing exercises investigated in this study produced modifications in
      the breathing pattern (e.g., increase in tidal volume and decrease in RR) as well
      as in thoracoabdominal motion (e.g., increase in abdominal contribution during
      diaphragmatic breathing), among others.

PMID- 25590448
TI  - Application of positive airway pressure in restoring pulmonary function and
      thoracic mobility in the postoperative period of bariatric surgery: a randomized
      clinical trial.
AB  - OBJECTIVE: To evaluate whether the application of bilevel positive airway
      pressure in the postoperative period of bariatric surgery might be more effective
      in restoring lung volume and capacity and thoracic mobility than the separate
      application of expiratory and inspiratory positive pressure. METHOD: Sixty
      morbidly obese adult subjects who were hospitalized for bariatric surgery and met
      the predefined inclusion criteria were evaluated. The pulmonary function and
      thoracic mobility were preoperatively assessed by spirometry and cirtometry and
      reevaluated on the 1st postoperative day. After preoperative evaluation, the
      subjects were randomized and allocated into groups: EPAP Group (n=20), IPPB Group
      (n=20) and BIPAP Group (n=20), then received the corresponding intervention:
      positive expiratory pressure (EPAP), inspiratory positive pressure breathing
      (IPPB) or bilevel inspiratory positive airway pressure (BIPAP), in 6 sets of 15
      breaths or 30 minutes twice a day in the immediate postoperative period and on
      the 1st postoperative day, in addition to conventional physical therapy. RESULTS:
      There was a significant postoperative reduction in spirometric variables
      (p<0.05), regardless of the technique used, with no significant difference among
      the techniques (p>0.05). Thoracic mobility was preserved only in group BIPAP
      (p>0.05), but no significant difference was found in the comparison among groups
      (p>0.05). CONCLUSION: The application of positive pressure does not seem to be
      effective in restoring lung function after bariatric surgery, but the use of
      bilevel positive pressure can preserve thoracic mobility, although this technique
      was not superior to the other techniques.

PMID- 25590449
TI  - Functional priorities reported by parents of children with cerebral palsy:
      contribution to the pediatric rehabilitation process.
AB  - BACKGROUND: Collaborative actions between family and therapist are essential to
      the rehabilitation process, and they can be a catalyst mechanism to the positive
      outcomes in children with cerebral palsy (CP). OBJECTIVES: To describe functional
      priorities established by caregivers of CP children by level of severity and age,
      and to assess changes on performance and satisfaction on functional priorities
      reported by caregivers, in 6-month interval. METHOD: 75 CP children, weekly
      assisted at Associacao Mineira de Reabilitacao, on physical and occupational
      therapy services. The following information was collected: gross motor function
      (Gross Motor Function Classification System-GMFCS) and functional priorities
      established by caregivers (Canadian Occupational Performance Measure-COPM). Data
      were collected in two moments, with a 6-month interval. RESULTS: The main
      functional demands presented by caregivers were related to self-care activities
      (48.2%). Parents of children with severe motor impairment (GMFCS V) pointed
      higher number of demands related to play (p=0.0036), compared to the other
      severity levels. Parents of younger children reported higher number of demands in
      mobility (p=0.025) and play (p=0.007), compared to other age groups. After 6
      months, there were significant increase on COPM performance (p=0.0001) and
      satisfaction scores (p=0.0001). CONCLUSIONS: Parents of CP children identified
      functional priorities in similar performance domains, by level of severity and
      age. Orienting the pediatric rehabilitation process to promote changes in
      functional priorities indentified by caregivers can contribute to the
      reinforcement of the parent-therapist collaboration.

PMID- 25590453
TI  - Happy birthday, Rolf Mulhaupt!

PMID- 25590450
TI  - Ground reaction forces during level ground walking with body weight unloading.
AB  - BACKGROUND: Partial body weight support (BWS) systems have been broadly used with
      treadmills as a strategy for gait training of individuals with gait impairments.
      Considering that we usually walk on level ground and that BWS is achieved by
      altering the load on the plantar surface of the foot, it would be important to
      investigate some ground reaction force (GRF) parameters in healthy individuals
      walking on level ground with BWS to better implement rehabilitation protocols for
      individuals with gait impairments. OBJECTIVE: To describe the effects of body
      weight unloading on GRF parameters as healthy young adults walked with BWS on
      level ground. METHOD: Eighteen healthy young adults (27 +/- 4 years old) walked
      on a walkway, with two force plates embedded in the middle of it, wearing a
      harness connected to a BWS system, with 0%, 15%, and 30% BWS. Vertical and
      horizontal peaks and vertical valley of GRF, weight acceptance and push-off
      rates, and impulse were calculated and compared across the three experimental
      conditions. RESULTS: Overall, participants walked more slowly with the BWS system
      on level ground compared to their normal walking speed. As body weight unloading
      increased, the magnitude of the GRF forces decreased. Conversely, weight
      acceptance rate was similar among conditions. CONCLUSIONS: Different amounts of
      body weight unloading promote different outputs of GRF parameters, even with the
      same mean walk speed. The only parameter that was similar among the three
      experimental conditions was the weight acceptance rate.

PMID- 25590458
TI  - Screening for cognitive impairment after stroke: A systematic review of
      psychometric properties and clinical utility.
AB  - OBJECTIVE: To systematically review the psychometric properties and clinical
      utility of cognitive screening tools post-stroke. DATA SOURCES: EMBASE, CINAHL,
      MEDLINE, PsychInfo. STUDY SELECTION: Studies testing the accuracy of screening
      tools for cognitive impairment after stroke. DATA EXTRACTION: Data regarding the
      participants, selection criteria, criterion/reference measure, cut-off score,
      sensitivity, specificity and positive and negative predicted values for the
      selected tools were extracted. Tools with sensitivity >= 80% and specificity >=
      60% were selected. Clinical utility was assessed using a previously validated
      tool and those scoring <6 were excluded. DATA SYNTHESIS: Twenty-one papers
      regarding 12 screening tools were selected. Only the Montreal Cognitive
      Assessment (MoCA) and Mini Mental State Examination (MMSE) met all psychometric
      and clinical utility criteria for any levels of cognitive impairment. However,
      the MMSE is most accurate to screen for dementia (cut-off score 23/24) and should
      only be used for this purpose. In addition, the following can be used to detect:
      * Any impairment: Addenbrooke's Cognitive Examination-Revised (ACE-R), Barrow
      Neurological Institute Screen for Higher Cerebral Functions (BNIS) and Cognistat.
      * Multiple-domain impairments: ACE-R, Telephone-MoCA or modified Telephone
      Interview for Cognitive Status (TICS). * Dementia: TICS; Cambridge Cognitive
      Examination; Rotterdam-Cambridge Cognitive Examination; Informant Questionnaire
      for Cognitive Decline in the Elderly (IQCODE) and short-IQCODE. The IQCODE and
      short-IQCODE are useful when the patient is unable to respond and an informant's
      view is required. CONCLUSION: The MoCA is the most valid and clinically feasible
      screening tool to identify stroke survivors with a wide range of cognitive
      impairments who warrant further assessment.

PMID- 25590459
TI  - A dual-responsive supra-amphiphilic polypseudorotaxane constructed from a water
      soluble pillar[7]arene and an azobenzene-containing random copolymer.
AB  - Macromolecular supra-amphiphiles refer to a kind of macromolecular amphiphiles
      whose hydrophlic and hydrophobic parts are connected by noncovalent forces. They
      have applications in various fields, such as drug delivery, sensor systems, and
      biomedical materials. Here we report a novel molecular recognition motif between
      a new thermoresponsive water-soluble pillar[7]arene (WP7) and an azobenzene
      derivative. Furthermore, we utilized this recognition motif to construct the
      first pillararene-based supra-amphiphilic polypseudorotaxane which can self
      assemble to form vesicles in water. Due to the dual-responsiveness of the
      molecular recognition motif (the thermoresponsiveness of WP7 and
      photoresponsiveness of azobenzene), the reversible transformations between solid
      nanospheres based on the self-assembly of the polymer backbone and vesicles based
      on the self-assembly of the supra-amphiphilic polypseudorotaxane were achieved by
      adjusting the solution temperature or UV-visible light irradiation. These dual
      responsive aggregation behaviors were further used in the controlled release of
      water-soluble dye calcein molecules. 

PMID- 25590460
TI  - Bilateral conjunctivitis in a returned traveller.

PMID- 25590461
TI  - "A Shrinking Kind of Life": Gay Men's Experience of Aging With HIV.
AB  - More people are living with HIV into midlife and older age. Although increased
      longevity brings new hope, it also raises unanticipated challenges--especially
      for gay men who never thought they would live into middle and older age. Middle
      aged and older people are more likely to face multiple comorbidities, yet many
      lack the necessary supports to help them adapt to the challenges of aging with
      HIV. This article presents the findings of a qualitative study developed to
      explore gay men's experience of aging with HIV. Multiple in-depth exploratory
      interviews were conducted with 15 gay-identified men living with HIV/AIDS over an
      18-month period. A systematic strategy data analysis consistent with grounded
      theory revealed a pattern of subtle adjustments to living with HIV that resulted
      in diminishing circles of social support and social involvement. This dynamic is
      referred to as "a shrinking kind of life," an in-vivo code built from the
      participant's own words. Four themes from the research (physical challenges, a
      magnitude of loss, internal changes, & stigma) are discussed. Conclusions include
      recommendations for future research and implications for practice in the field.
      Practitioners knowledgeable of the factors that impact their social involvement
      can empower gay men through individual and group interventions to confront a
      shrinking kind of life and define for themselves what it means to optimally age
      with HIV.

PMID- 25590462
TI  - Symptoms, quality of life and level of functioning of traumatized refugees at
      psychiatric trauma clinic in Copenhagen.
AB  - OBJECTIVE: To characterize physical and mental health in trauma exposed refugees
      by describing a population of patients with regard to background, mental health
      history and current health problems; and to identify pre- and post-migratory
      predictors of mental health. METHOD: All patients receiving treatment at the
      Psychiatric Trauma Clinic for Refugees in Copenhagen from April 2008 to February
      2010 completed self-rating inventories on symptoms of PTSD, depression and
      anxiety as well as level of functioning and quality of life before treatment.
      Then, associations of pre and post migratory factors with mental health were
      explored using linear and logistic regression and Pearson's correlation
      coefficients. RESULTS: Among the patients, the prevalence of depression, somatic
      disease, pain, psychotic symptoms co-existing with PTSD and very low level of
      functioning was high. Persecution, being an ex-combatant and living currently in
      social isolation were significantly associated with PTSD arousal symptoms and
      self-reported pain. CONCLUSIONS: New treatment modalities should seek to address
      all of the symptoms and challenges of the patients including psychotic and
      somatic symptoms and social isolation, and studies of treatment effect should
      clarify all co-morbidities so that comparable populations can be included in
      treatment evaluation studies.

PMID- 25590463
TI  - Psychotherapy with traumatised refugees--the design of a randomised clinical
      trial.
AB  - There is little evidence as to which kind of psychotherapy is the most effective
      in the treatment of traumatised refugees. At the Competence Center for
      Transcultural Psychiatry, a series of clinical trials have been conducted since
      2008. The first results are pending publication. The aim of this paper is to
      discuss some of the challenges in adapting Cognitive Behavioural Therapy (CBT) to
      the treatment of traumatised refugees, as well as describe a randomised clinical
      trial designed to test two such adaptations. In the described trial one group
      receives CBT with a focus on cognitive restructuring while the other group
      receives CBT focusing on Stress Management. A main goal of this setup is to test
      whether some, perhaps even most, of the traumatised refugees referred to
      treatment, may benefit from a more direct focus on current stress, and its
      alleviation through simple, repetitive exercises, compared to a focus on
      analysing and changing thought patterns. 

PMID- 25590464
TI  - Activity of daily living performance amongst Danish asylum seekers: a cross
      sectional study.
AB  - OBJECTIVE: The aim of this study was to evaluate the extent of Activities of
      Daily Living (ADL) ability impairment in newly arrived Danish asylum seekers. It
      was hypothesized that exposure to trauma and torture would negatively influence
      ADL performance and that measures of ADL ability would be lower in individuals
      exposed to torture as compared to the non-tortured. SUBJECTS: Forty-three newly
      arrived asylum seekers aged 20-50 years, from Iran, Afghanistan and Syria, were
      consecutively included in the study. METHOD: ADL ability was assessed with the
      observation-based test Assessment of Motor and Process Skills (AMPS). Interviews
      were based on questionnaires about torture exposure, WHO-5 Wellbeing Index, Major
      Depression Inventory and Pain Detect Questionnaire. All participants were
      interviewed and tested using a linguistic interpreter. RESULTS: Thirty three
      (77%) participants reported exposure to torture. The tortured did not differ
      significantly from the nontortured on measures of ADL ability (two-sample t
      tests: Motor, p= 0.36; Process, p= 0.82). ADL performance impairment was observed
      in the overall study sample. Twelve had motor and 15 process ability measures
      below age norms and 2 below both AMPS motor and process cut-offs for effortless
      and efficient ADL performance. There were statistically significant - weak to
      moderate - correlations between self-reported psychological distress, VAS average
      pain, pain distribution and the AMPS measures. CONCLUSION: The study results
      supported significant ADL ability impairment in tortured as well as non-tortured
      newly arrived asylum seekers. Implementation of performance-based evaluation of
      ADL ability as part of the initial medical screening of this particular
      population should be considered.

PMID- 25590465
TI  - Hospitalizations for patients aged 85 and over in the United States, 2000-2010.
AB  - KEY FINDINGS: Data from the National Hospital Discharge Survey. In 2010, adults
      aged 85 and over accounted for only 2% of the U.S. population but 9% of hospital
      discharges. From 2000 through 2010, the rate of hospitalizations for adults aged
      85 and over declined from 605 to 553 hospitalizations per 1,000 population, a 9%
      decrease. The rate of fractures and other injuries was higher for adults aged 85
      and over (51 per 1,000 population) than for adults aged 65-74 (9 per 1,000
      population) and 75-84 (23 per 1,000 population). Adults aged 85 and over were
      less likely than those aged 65-74 and 75-84 to be discharged home and more likely
      to die in the hospital. From 2000 through 2010, the number of adults aged 85 and
      over in the United States rose 31%, from 4.2 million to 5.5 million, and in 2010,
      this age group represented almost 14% of the population aged 65 and over (1). It
      is estimated that by 2050, more than 21% of adults over age 65 will be aged 85
      and over (2). Given this increase, adults aged 85 and over are likely to account
      for an increasing share of hospital utilization and costs in the coming years
      (3). This report describes hospitalizations for adults aged 85 and over with
      comparisons to adults aged 65-74 and 75-84.

PMID- 25590466
TI  - The diagnostic value of clinical symptoms in women and men presenting with chest
      pain at the emergency department, a prospective cohort study.
AB  - BACKGROUND: Previous studies suggested that diagnosing coronary artery disease
      (CAD) is more difficult in women than in men. Studies investigating the
      predictive value of clinical signs and symptoms and compare its combined
      diagnostic value between women and men are lacking. METHODOLOGY: Data from a
      large multicenter prospective study was used. Patients admitted to the emergency
      department (ED) with chest pain but without ST-elevation were eligible. The
      endpoint was proven CAD, defined as a significant stenosis at angiography or the
      diagnosis of a non-ST-elevation myocardial infarction or cardiovascular death
      within six weeks after presentation at the ED. Twelve clinical symptoms and seven
      cardiovascular risk factors were collected. Potential predictors of CAD with a p
      value <0.15 in the univariable analysis were included in a multivariable model.
      The diagnostic value of clinical symptoms and cardiovascular risk factors was
      quantified in women and men separately and areas under the curve (AUC) were
      compared between sexes. RESULTS: A total of 2433 patients were included. We
      excluded 102 patients (4%) with either an incomplete follow up or ST-elevation.
      Of the remaining 2331 patients 43% (1003) were women. CAD was present in 111
      (11%) women and 278 (21%) men. In women 11 out of 12 and in men 10 out of 12
      clinical symptoms were univariably associated with CAD. The AUC of symptoms alone
      was 0.74 (95%CI: 0.69-0.79) in women and 0.71 (95%CI: 0.68-0.75) in men and
      increased to respectively 0.79 (95%CI: 0.74-0.83) in women versus 0.75 (95%CI:
      0.72-0.78) in men after adding cardiovascular risk factors. The AUCs of women and
      men were not significantly different (p-value symptoms alone: 0.45, after adding
      cardiovascular risk factors: 0.11). CONCLUSION: The diagnostic value of clinical
      symptoms and cardiovascular risk factors for the diagnosis of CAD in chest pain
      patients presenting on the ED was high in women and men. No significant
      differences were found between sexes.

PMID- 25590468
TI  - Impact of xylomethazoline on eustachian tube function in healthy participants.
AB  - INTRODUCTION: The use of decongestants is common in otitis media eustachian tube
      (ET) dysfunction. However, the underlying mechanism and the type of action on the
      complex middle ear pressure equalization system are poorly understood. Here, by
      use of the pressure chamber, we investigated the impact of intranasal
      decongestive therapy (xylomethazoline) on ET function. MATERIALS AND METHODS:
      Thirty healthy participants (60 ears) were exposed to a predetermined profile of
      phases of compression and decompression in a hypobaric and hyperbaric pressure
      chamber. ET opening pressure, ET opening duration, ET opening frequency, and ET
      closing pressure were determined before and after intranasal application of
      xylomethazoline. RESULTS: A significantly higher number of ET openings (ET
      opening frequency) in passive equalization condition could be measured after
      application of decongestants than before. No significant difference could be
      found in the values of ET opening pressure, ET opening duration, and ET closing
      pressure parameters before in comparison with the values after application of
      xylomethazoline. CONCLUSION: We conclude that xylomethazoline might only have a
      minor effect during active and passive middle ear pressure equalization. Larger
      cohorts and targeted application of decongestants should be tested to confirm
      these preliminary data and to find new evidence on the effects of decongestants.

PMID- 25590469
TI  - A 3-mm margin completely removes dermatofibromas: a study of 151 cases.

PMID- 25590470
TI  - Reconstruction of a large defect of the glabella and forehead.

PMID- 25590467
TI  - The coagulopathy of acute sepsis.
AB  - PURPOSE OF REVIEW: Sepsis, defined by the presence of infection and host
      inflammation, is a lethal clinical syndrome with an increasing mortality rate
      worldwide. In severe disease, the coagulation system becomes diffusely activated,
      with consumption of multiple clotting factors resulting in disseminated
      intravascular coagulation (DIC). When present, DIC portends a higher mortality
      rate. Understanding the mechanisms that tie inflammation and diffuse thrombosis
      will allow therapeutic interventions to be developed. The coagulopathy of acute
      sepsis is a dynamic process that is time and disease burden specific. Whole-blood
      testing of coagulation may provide more clinically useful information than the
      classical tests. Natural anticoagulants that regulate thrombosis are
      downregulated in sepsis. Patients may benefit from the modulation of the
      coagulation system when systemic inflammation and hypercoagulopathy exist. Proper
      timing of anticoagulant therapy may ultimately lead to decreased incidence of
      multisystem organ dysfunction. RECENT FINDINGS: The pathogenesis of coagulopathy
      in sepsis is driven by an upregulation of procoagulant mechanisms and
      simultaneous downregulation of natural anticoagulants. Inflammation caused by the
      invading organism is a natural host defense that cannot be eliminated during
      treatment. Successful strategies to prevent multisystem organ dysfunction center
      on stratifying patients at high risk for DIC and restoring the balance of
      inflammation and coagulation. SUMMARY: The prevention of DIC in septic patients
      is a key therapeutic target in preventing death from multisystem organ failure.
      Stratifying patients for therapy using thromboelastometry, specific markers for
      DIC, and composite scoring systems is an area of growing research.

PMID- 25590471
TI  - Analysis of incidence of bulla formation after tattoo treatment using the
      combination of the picosecond Alexandrite laser and fractionated CO2 ablation.
AB  - BACKGROUND: The picosecond Alexandrite laser has shown increased efficacy in
      tattoo removal in comparison to Q-switched lasers. However, bulla formation is a
      well-known and expected side effect of this novel treatment and causes patient
      discomfort. OBJECTIVE: To analyze the incidence of bulla formation after tattoo
      treatment using the combination of the picosecond Alexandrite laser and
      fractionated CO2 ablation. MATERIALS AND METHODS: This is a retrospective chart
      review to determine the incidence of bulla formation after laser tattoo removal
      in 95 patients who were treated with either with the picosecond Alexandrite laser
      alone or in combination with fractional CO2 ablation. RESULTS: Twenty-six
      patients (32%) treated with the picosecond laser alone experienced blistering,
      whereas none of the patients treated with the combination of the picosecond laser
      and fractionated CO2 ablation experienced blistering. The difference in incidence
      of bulla formation between the 2 groups was found to be statistically significant
      (p < .05). CONCLUSION: This study shows a significant decrease in bulla formation
      associated with tattoo treatment when fractionated CO2 ablation is added to the
      picosecond Alexandrite laser, which is consistent with observations from a
      previous case series. This is important because decreasing extensive blistering
      likely results in increased patient satisfaction and willingness to return for
      future treatments.

PMID- 25590473
TI  - Five-year outcomes of wide excision and Mohs micrographic surgery for primary
      lentigo maligna in an academic practice cohort.
AB  - BACKGROUND: Wide local excision with 5-mm margins is the standard of care for
      lentigo maligna (LM). Mohs micrographic surgery (MMS) is used increasingly to
      treat this tumor. OBJECTIVE: To study the authors' experience with these 2
      approaches. MATERIALS AND METHODS: Primary LM cases treated at the authors'
      institution from January 1, 1995, through December 31, 2005, were studied
      retrospectively. Main outcome measures were recurrence and outcomes after
      treatment for recurrence. RESULTS: In total, 423 LM lesions were treated in 407
      patients: 269 (64%) with wide excision and 154 (36%) with MMS. In the MMS group
      (primarily larger head and neck lesions with indistinct clinical margins),
      recurrence rates were 3 of 154 (1.9%). In the wide excision group (primarily
      smaller, nonhead and neck, or more distinct lesions), recurrence rates were 16 of
      269 (5.9%). Each of the 16 recurrences was biopsy proven and treated surgically:
      6 by standard excision and 10 by MMS. CONCLUSION: This follow-up study of LM
      surgical treatments shows excellent outcomes for wide excision and MMS. Because
      this is a nonrandomized retrospective study, no direct comparisons between the 2
      treatments can be made. When recurrences occurred, repeat surgery, either
      standard excision or MMS, was usually sufficient to provide definitive cure.

PMID- 25590472
TI  - Improved upper blepharoplasty outcome using an internal intradermal suture
      technique: a prospective randomized study.
AB  - OBJECTIVE: To assess whether a suture technique in upper blepharoplasty may be
      the cause of differences in the occurrence of suture abscess formation and focal
      inflammation. MATERIALS AND METHODS: A Level I, randomized controlled trial. The
      upper blepharoplasty wound was closed with a running intradermal suture. External
      intradermal suturing implied that this suture was started by initially passing it
      through the intact skin adjacent to the wound. In contrast, internal intradermal
      suturing meant the intradermal suture was not started in the adjacent skin but
      simply within the wound itself. One week and 6 weeks after surgery, the presence
      of suture abscesses and focal inflammation was assessed at the entrance and exit
      of the sutures. RESULTS: After 1 week, 12 abscesses (40.0%) were found at the
      medial side of the externally sutured upper eyelids and 4 abscesses (13.3%) in
      the internally sutured upper eyelids (p = .02). The presence of erythema and
      edema after 1 week was also significantly lower in internally sutured upper
      eyelids (p = .02). CONCLUSION: In this series, the method of starting the suture
      (internal vs external) at the medial side of an upper blepharoplasty wound was
      associated with a statistically significant reduction in the incidence of medial
      wound inflammation and suture abscess formation at a 1-week follow-up.

PMID- 25590474
TI  - The effects of IL-2 and Treg cells on dendritic cell homeostasis are mediated
      indirectly via activation of conventional T cells.
AB  - DC homeostasis is influenced by multiple factors, including the availability of
      GM-CSF and Flt3L, both of which exert positive effects on DC differentiation and
      survival. IL-2 and Treg cells have recently been proposed as negative regulators
      of DC numbers. It remains unclear whether their effects in immunosufficient mice
      are direct, or are mediated via activation of conventional T cells in response to
      deficiencies of IL-2 and/or Treg cells. Using a number of in vivo models, we have
      assessed the role of IL-2 and Treg-cell number on conventional splenic and LN
      DCs. We have found no evidence for a direct role of IL-2 or Treg cells in
      negatively regulating DC number. Our data indicate that the expansion of DCs in
      the absence of either IL-2 or Treg cells is an indirect effect secondary to the
      activation and proliferation of conventional T cells. 

PMID- 25590475
TI  - Slide over chest x-ray.

PMID- 25590476
TI  - To sleep or not to sleep: that is the question.

PMID- 25590477
TI  - The effect of general anesthesia versus intravenous sedation on diagnostic yield
      and success in electromagnetic navigation bronchoscopy.
AB  - BACKGROUND: Navigational bronchoscopy is utilized to guide biopsies of peripheral
      lung nodules and place fiducial markers for treatment of limited stage lung
      cancer with stereotactic body radiotherapy. The type of sedation used for this
      procedure remains controversial. We performed a retrospective chart review to
      evaluate the differences of diagnostic yield and overall success of the procedure
      based on anesthesia type. METHODS: Electromagnetic navigational bronchoscopy was
      performed using the superDimension software system. Once the targeted lesion was
      within reach, multiple tissue samples were obtained. Statistical analysis was
      used to correlate the yield with the type of sedation among other factors. A
      successful procedure was defined if a diagnosis was made or a fiducial marker was
      adequately placed. RESULTS: Navigational bronchoscopy was performed on a total of
      120 targeted lesions. The overall complication rate of the procedure was 4.1%.
      The diagnostic yield and success of the procedure was 74% and 87%, respectively.
      Duration of the procedure was the only significant difference between the general
      anesthesia and IV sedation groups (mean, 58 vs. 43 min, P=0.0005). A larger tumor
      size was associated with a higher diagnostic yield (P=0.032). All other variables
      in terms of effect on diagnostic yield and an unsuccessful procedure did not meet
      statistical significance. CONCLUSIONS: Navigational bronchoscopy is a safe and
      effective pulmonary diagnostic tool with relatively low complication rate. The
      diagnostic yield and overall success of the procedure does not seem to be
      affected by the type of sedation used.

PMID- 25590478
TI  - Role of ultrasonography in the diagnosis and management of pneumothorax following
      transbronchial lung biopsy.
AB  - BACKGROUND: Pneumothorax (PTX) following flexible bronchoscopy (FB) and
      transbronchial lung biopsy (TBLB) occurs in 1% to 6% of cases. Chest radiography
      (CXR) is therefore routinely requested to detect PTX following TBLB. The
      objective of this study was to prospectively evaluate the accuracy of ultrasound
      (US) in the detection of post-TBLB PTX. METHODS: Consecutive patients undergoing
      elective FB at a tertiary care hospital were included in the study. A real-time
      US was used to rule out PTX immediately after FB. PTX was defined by the absence
      of lung sliding and the presence of "lung point" and "stratosphere" sign. In
      cases of PTX, US was repeated at 2-hour intervals, and the resolution or
      progression of PTX was assessed based on dynamic shifts of the "lung points."
      RESULTS: A total of 379 FB procedures and 113 TBLB were performed during the
      study period. PTX occurred in 8 (2.1%) patients. US detected all cases of PTX,
      whereas CXR missed 1 PTX. The sensitivity, specificity, and overall accuracy for
      US were 100% as compared with sensitivity of 87.5% and accuracy of 99.6% for the
      CXR group. Shift of the "lung point" below the mid-thoracic line implied the
      progression of PTX and hence favored intervention (performed in 3 cases), whereas
      conservative management was done in cases where "lung point" shifted above mid
      thoracic line. CONCLUSIONS: This study demonstrates a good sensitivity of US in
      detecting PTX following TBBL. Bedside US may become the method of choice for
      diagnosing, monitoring, and managing PTX after TBLB.

PMID- 25590479
TI  - Assessment of the new thin convex probe endobronchial ultrasound bronchoscope and
      the dedicated aspiration needle: a preliminary study in the porcine lung.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) allows for accurate minimally invasive mediastinal lymph node staging
      of lung cancer. The current convex probe EBUS (CP-EBUS) has limitations in the
      access to certain N1 lymph nodes (lobar and segmental) because of its size. The
      aim of this study was to assess the new thin CP-EBUS (TCP-EBUS) and an aspiration
      needle for sampling of N1 lymph nodes in a porcine model. METHODS: The prototype
      TCP-EBUS (BF-Y0046, Olympus Medical Systems Corp.) with a thinner tip (5.9 mm)
      and larger bending angle (170 degrees upward) was used. Accessibility,
      operability, and TBNA capability of the TCP-EBUS were assessed and compared with
      the current CP-EBUS using porcine lungs. The endoscopic visibility range and the
      maximum reach were evaluated at the left upper lobe bronchus, tracheobronchus,
      and right lower lobe bronchus. The prototype aspiration needle (Olympus Medical
      Systems Corp.) was used for EBUS-TBNA. RESULTS: In all of the evaluated bronchi
      (n=9), the TCP-EBUS had a greater reach (14.7 mm in the endoscopic visibility
      range, 16.0 mm in the maximum reach) than the current CP-EBUS. The TCP-EBUS was
      able to visualize 1 to 3 distal bifurcations farther compared with the current CP
      EBUS. Adequate lymph node sampling from lobar and segmental lymph nodes was
      possible using the aspiration needle. CONCLUSIONS: The TCP-EBUS has improved
      accessibility to peripheral bronchi with excellent operability and is capable of
      sampling lobar and segmental lymph nodes using the dedicated aspiration needle.

PMID- 25590480
TI  - Use of endobronchial ultrasound to evaluate nonthrombotic endovascular lesions in
      pulmonary arteries: a systematic review.
AB  - BACKGROUND: The finding of a filling defect in a pulmonary artery (PA) sometimes
      raises the possibility of cancer. Endobronchial ultrasound (EBUS)-guided
      transbronchial needle aspiration (TBNA) may confirm the underlying nature of the
      endovascular lesion. However, little is known about the use of this procedure for
      this purpose. METHODS: We searched PubMed and abstracts of major international
      conferences. RESULTS: There was a total of 12 cases: 8 female, 3 male, and 1
      unknown. The median (range) age was 60 (51 to 79) years. EBUS was performed to
      evaluate mass-like lesion involving the PA (n=5), persistent or progressive
      filling defects in the PA despite anticoagulation (n=3), filling defect in the PA
      with multiple areas of consolidation, air-fluid levels in the lung (n=1), and
      hilar density (n=1). Moreover, an endovascular lesion was incidentally noted in
      the PA during EBUS for evaluating lymph nodes (n=2). EBUS-TBNA was diagnostic in
      9 of the 10 cases in which it was performed. The final diagnoses were: sarcoma
      (n=6), lung cancer (n=2), thyroid cancer (n=1), renal cell cancer (n=1), melanoma
      (n=1), and pulmonary embolism (n=1). The cancer was a recurrence in 6 of the 7
      cases with a known history of cancer. CONCLUSIONS: EBUS should be considered as a
      possible method for evaluating endovascular lesions when PA sarcoma or tumor
      macroembolism is suspected.

PMID- 25590481
TI  - Confocal laser endomicroscopy for diagnosis and monitoring of pulmonary alveolar
      proteinosis.
AB  - BACKGROUND: The diagnosis of pulmonary alveolar proteinosis (PAP) is based on
      computed tomography, histology, and antibodies to granulocyte-macrophage colony
      stimulating factor. The role of a novel technique for imaging cells and elastin
      during endoscopy, probe-based confocal laser endomicroscopy (pCLE), has not yet
      been investigated in PAP patients. The aim of the present study was to estimate
      the value of pCLE in the PAP diagnosis and treatment in comparison with the
      findings of high-resolution computed tomography (HRCT) before and after whole
      lung lavage. METHODS: In vivo pCLE was performed during bronchoscopy in 6 male
      patients with PAP before and after whole-lung lavage. In certain lung segments,
      pCLE was followed by HRCT. RESULTS: During the in vivo pCLE, we found
      characteristic signs of PAP: a fluorescent floating amorphous substance in the
      alveoli lumen sticking to conglomerates along with alveolar macrophages. These
      features were present to a lesser extent after a whole-lung lavage. pCLE revealed
      specific PAP features not only in segments with crazy-paving and ground-glass
      opacity, but also in segments without HRCT findings. CONCLUSIONS: The alveolar
      imaging in PAP patients is able to reveal characteristic changes, both in the
      presence and in the absence of HRCT findings. Therefore, pCLE may be a helpful
      tool for the diagnosis and whole-lung lavage therapy. Our data prove that
      accumulation of lipoproteinaceous substances within the alveoli at PAP is a
      diffuse but not a patchy process.

PMID- 25590482
TI  - Critical airway obstruction: challenges in airway management and ventilation
      during therapeutic bronchoscopy.
AB  - BACKGROUND: Endobronchial interventions are used to alleviate symptoms of airway
      stenosis. The ventilatory management may be challenging during these procedures,
      and may influence the choice of airway device. We report our experiences from 902
      procedures. METHODS: Patients undergoing interventional bronchoscopy procedures
      were consecutively registered from 1999 to 2012. Critical airway obstruction
      (CAO) was defined as stridor, tracheal diameter <5 mm, stenosis of both the main
      bronchi, or clots/tumor fragments occluding the trachea or both main bronchi.
      Choice of airway, ventilation strategy, and survival are reported. Results are
      presented as median (interquartile range), and P<=0.05 was considered
      significant. RESULTS: A total of 561 patients underwent 902 interventional
      bronchoscopy procedures (mechanical debulking, laser resection, balloon
      dilatation, and stent placement). The procedures were performed using flexible
      bronchoscope through an endotracheal tube (68.2%) or laryngeal mask airway
      (10.4%), or by rigid bronchoscopy (9.3%). All patients were primarily ventilated
      by volume-controlled ventilation. CAO was classified in 60 procedures, with more
      frequent use of laryngeal mask airway (21.7%), and change of airway device in
      20/60 procedures. The survival for patients with malignant disease with or
      without CAO was 100 and 182 days, respectively, with 90 days survival probability
      of 0.65 and 0.51 (P=0.14). CONCLUSIONS: Bronchoscopic treatment in patients with
      CAO may require a change of ventilatory and airway strategy during the procedure.
      Despite various challenges in the management of patients with CAO, the short-term
      survival in these patients is comparable to that in patients without CAO.

PMID- 25590483
TI  - Effectiveness of thoracoscopic talc pleurodesis in the management of complicated
      spontaneous pneumothorax.
AB  - BACKGROUND: Complicated (recurring or persistent) spontaneous pneumothorax
      requires intervention either by surgical or nonsurgical pleurodesis or other
      interventions. As for high-risk patients, aggressive interventions may be
      associated with morbidity, the safety and effectiveness of less aggressive
      alternative interventions like thoracoscopic talc pleurodesis (TTP) should be
      evaluated. METHODS: Data were extracted on patients who had undergone TTP for
      complicated spontaneous pneumothorax at Interventional Clinic, University
      Hospital, Brussels, Belgium. The complications, length of hospital stay, and
      success rate over a 24-month period were studied. RESULTS: A total of 41 TTP
      procedures were performed for 25 (61%) cases of primary spontaneous pneumothorax
      and for 16 (39%) cases of secondary spontaneous pneumothorax. Twenty-four cases
      were first episodes, whereas it was a recurrence in 17. Of 4 patients with
      blebs/bullae, 2 had recurrence after TTP.No patient had acute respiratory
      distress syndrome or any other serious complication after TTP. Recurrence rates
      after TTP in primary and secondary spontaneous pneumothorax were 9.5% and 25% at
      24 months, respectively. The mean length of hospital stay after TTP was 3+/-3.2
      days. CONCLUSIONS: TTP is a safe and effective intervention in complicated
      spontaneous pneumothorax.

PMID- 25590484
TI  - Tracheal fibroepithelial polyp.

PMID- 25590485
TI  - Thoracic metastasis from renal cell carcinoma: bronchoscopic and EBUS images.

PMID- 25590486
TI  - Inflammatory myofibroblastic tumor of the trachea in the pediatric age group:
      case report and systematic review of the literature.
AB  - Inflammatory myofibroblastic tumors are uncommon tumors, which present as
      solitary masses in the pulmonary parenchyma. Tracheal involvement by these tumors
      is extremely rare and can be misdiagnosed as asthma. The closest histologic
      differential diagnoses are IgG4-related sclerosing pseudotumors, which are
      differentiated by IgG4 positivity. Fifty percent of inflammatory myofibroblastic
      tumors are positive for anaplastic lymphoma kinase gene rearrangements. The
      treatment modality of choice is surgical resection with therapeutic bronchoscopy
      reserved for patients presenting with acute airway obstruction or in those
      unwilling for surgery. New and upcoming treatments include anaplastic lymphoma
      kinase inhibitors like crizotinib. 

PMID- 25590487
TI  - Endobronchial glomus tumor.
AB  - We report a case of a 52-year-old patient who had undergone a bladder resection
      and an ileal conduit for a transitional cell carcinoma. He then presented with a
      short history of hemoptysis 3 months later. Rigid bronchoscopy was performed
      revealing an endobronchial lesion, which was removed via laser and debulking
      method without complications. Histopathologic examination confirmed it to be a
      benign endobronchial glomus tumor. On the basis of our literature search, this is
      the 34th reported case of glomus tumor arising from the respiratory tract,
      seventh reported case of an endobronchial glomus tumor treated bronchoscopically,
      and the first possibly coincidental finding in relation to a patient with primary
      transitional bladder cell carcinoma. 

PMID- 25590488
TI  - Tension bulla: a cause of reversible pulmonary hypertension.
AB  - A tension pneumothorax represents a medical emergency warranting urgent diagnosis
      and treatment. A rapidly expanding bulla may resemble the same clinical
      presentation but requires an entirely different treatment. A 53-year-old woman
      presented with increasing shortness of breath and her physical examination and
      chest x-ray were interpreted as showing a tension pneumothorax. A chest tube was
      placed which did not resolve the process. Placement of a second chest tube was
      likewise unsuccessful. A chest CT was then performed and was interpreted as
      showing an unresolved tension pneumothorax, despite seemingly adequate placement
      of the 2 chest tubes. Further review of the CT showed the border of a giant bulla
      and a tentative diagnosis was made of a rapidly expanding bulla with tension
      physiology. Echocardiogram revealed significant pulmonary hypertension. The bulla
      was surgically excised, the patient had marked improvement in her clinical
      symptoms and signs, and echocardiographic follow-up showed complete resolution of
      the pulmonary hypertension. 

PMID- 25590489
TI  - Incidental tracheal diverticulum discovered 30 years after tracheo-esophageal
      fistula repair.
AB  - Tracheo-esophageal fistula is a well-described congenital abnormality treated
      surgically upon diagnosis. Although respiratory-related and reflux-related
      complications are frequent, recurrent fistula and diverticulum can occur. This
      case report describes the rare occurrence of a gross type B fistula repaired at
      birth, which was then asymptomatic for nearly 30 years until presentation with
      chest pain. Upon workup, the patient was found to have an isolated tracheal
      diverticulum without recurrent fistula. We highlight the need for a focused
      workup despite the length of time since fistula repair and the varied treatment
      modalities described in the literature. 

PMID- 25590490
TI  - Cryotechnology in diagnosing and treating lung diseases.
AB  - Cryotechnology has been used in treating lung cancer for many years, now it is
      emerging to have a new indication in diagnosing lung diseases. Cryoprobe
      transbronchial lung biopsy has been introduced into clinical practice as a new
      technique, providing a larger biopsy specimen, potentially improving the
      diagnostic yield of transbronchial biopsies in parenchymal lung diseases.
      Although recent small pilot studies suggest that cryotransbronchial lung biopsies
      are comparable to conventional transbronchial biopsies in terms of diagnostic
      yield and safety profile in lung transplant patients, cryoprobe transbronchial
      lung biopsy is still being evaluated and its role in clinical practice is not
      well defined. Cryotherapy has been proven as a safe and effective method to
      debulk endobronchial lesions, providing palliation for advanced central
      obstructive tumors. Its use and efficacy is also studied in direct cryosurgery
      and percutaneous application in lung cancer. Cryoprobes can also be used to
      extract foreign bodies from the airways by causing cryoadhesion. We aim to
      summarize the therapeutic and diagnostic application of cryotechnology in
      pulmonary diseases. 

PMID- 25590491
TI  - Malignant tracheal-mediastinal-parenchymal-pleural fistula after chemoradiation
      plus bevacizumab: management with a Y-silicone stent inside a metallic covered
      stent.
AB  - Tracheal or bronchial-mediastinal fistulas are a rare entity associated to high
      mortality. We report a case of a 58-year-old man with an unresectable non-small
      cell carcinoma of the lung, treated with chemoradiation followed by bevacizumab.
      Approximately, 6 weeks after starting bevacizumab he developed a severe cough
      with copious secretions He could not lie supine due to the feeling of drowning.
      Investigations revealed a large tracheo-mediastinal-parenchymal-pleural fistula.
      Palliative management was offered with interventional bronchoscopic techniques.
      He was found to have a large central airway defect that obliterated almost 40% of
      the trachea. Under general anesthesia and positive pressure ventilation, a unique
      approach was used to rebuild an eroded tracheal and right main stem bronchial
      wall. A self-expanding metallic stent (SEMS) was placed to provide a scaffold of
      support, whereas a Dumon Y-stent was placed inside the SEMS. This combination
      allowed for a patent, stable airway; recreating the normal anatomy in a minimally
      invasive manner walling off the fistula. The patient was discharged 2 days after
      the bronchoscopic intervention, with significant palliation of his
      symptomatology. Eighteen months later, the upper lobe cavity persists with a
      stable airway and stents perfectly positioned with clinically insignificant
      evidence of stent related granulation in the upper trachea. 

PMID- 25590492
TI  - Tracheal leiomyoma resected with endobronchial electrocautery snare.
AB  - Tracheobronchial leiomyoma is a rare benign tumor, which comprises about 2% of
      benign tumors of the lower respiratory tract. Bronchoscopic intervention is a
      minimally invasive treatment, but incomplete resection or recurrence has been
      reported. We report a case of a 76-year-old woman with a tracheal tumor of 14 mm
      in diameter incidentally detected on chest computed tomography. Bronchoscopic
      examination revealed a smooth polypoid tumor which pedunculated from the left
      side of the cartilaginous tracheal wall. An endobronchial electrocautery snare
      with flexible bronchoscope was successfully used under general anesthesia and
      with intubation. The resected specimen was pathologically consistent with
      leiomyoma. Bronchoscopic intervention can yield successful treatment of
      pedunculated tracheobronchial leiomyomas, although surgical resection should also
      be considered in cases of broad-based or iceberg-type leiomyomas because of the
      risk of incomplete resection or recurrence. 

PMID- 25590493
TI  - The value of endobronchial ultrasound transbronchial needle aspiration in normal
      positron emission tomography in lung cancer.

PMID- 25590494
TI  - Difficult Removal of Montgomery T-tube.

PMID- 25590495
TI  - Anti-tumor activity of miR-17 in melanoma.

PMID- 25590496
TI  - Nonnatural deaths among users of illicit drugs: pathological findings and illicit
      drug abuse stigmata.
AB  - The aim of the study was to provide information on illicit drug abuse stigmata
      and general pathological findings among an adult narcotic drug-using population
      aged 20 to 59 years whose death was nonnatural. A total of 1603 medicolegal
      autopsy reports from 2000 to 2009 concerning cases positive for morphine, heroin,
      amphetamines, ecstasy, cannabis, LSD (lysergic acid diethylamide), PCP
      (phencyclidine), and high levels of GHB (gamma-hydroxybutyric acid) in addition
      to methadone and buprenorphine were investigated. Reported findings of hepatitis,
      portal lymphadenopathy, recent injection marks, drug user's equipment, and
      numbers of significant pathological conditions were registered and analyzed
      according to cases positive for opiates, opioids (OPs), and central nervous
      system (CNS)-stimulating illicit drugs, respectively. Of the selected cases, 1305
      were positive for one or more opiate or OP. Cases positive for OPs had
      significantly more findings of noninfectious pathological conditions. Hepatitis,
      portal lymphadenopathy, recent injections marks findings of drug user's equipment
      were all findings found more frequently among the opiate OP-positive individuals.
      Portal lymphadenopathy was significantly more often found in cases with hepatitis
      than in cases with other or no infection. In the population positive for CNS
      stimulants, hepatitis recent injection marks were more frequent findings than in
      the CNS stimulant-negative group, irrespective of whether they were opiate OP
      positive or negative.

PMID- 25590498
TI  - Reply to Letter: "Poorer Survival for Stage IIa Patients After Minimally Invasive
      Esophagectomy".

PMID- 25590497
TI  - Ninety-day Postoperative Mortality Is a Legitimate Measure of
      Hepatopancreatobiliary Surgical Quality.
AB  - OBJECTIVE: To investigate the legitimacy of 90-day mortality as a measure of
      hepatopancreatobiliary quality. BACKGROUND: The 90-day mortality rate has been
      increasingly but not universally reported after hepatopancreatobiliary surgery.
      The legitimacy of this definition as a measure of surgical quality has not been
      evaluated. METHODS: We retrospectively reviewed the causes of all deaths that
      occurred within 365 postoperative days in patients undergoing hepatectomy (n =
      2811) and/or pancreatectomy (n = 1092) from January 1997 to December 2012. The
      rates of surgery-related, disease-related, and overall mortality within 30 days,
      within 30 days or during the index hospitalization, within 90 days, and within
      180 days after surgery were calculated. RESULTS: Seventy-nine (3%) surgery
      related deaths and 92 (3%) disease-related deaths occurred within 365 days after
      hepatectomy. Twenty (2%) surgery-related deaths and 112 (10%) disease-related
      deaths occurred within 365 days after pancreatectomy. The overall mortality rates
      at 99 and 118 days optimally reflected surgery-related mortality after
      hepatobiliary and pancreatic operations, respectively. The 90-day overall
      mortality rate was a less sensitive but equivalently specific measure of surgery
      related death. CONCLUSIONS AND RELEVANCE: The 99- and 118-day definitions of
      postoperative mortality optimally reflected surgery-related mortality after
      hepatobiliary and pancreatic operations, respectively. However, among commonly
      reported metrics, the 90-day overall mortality rate represents a legitimate
      measure of surgical quality.

PMID- 25590499
TI  - Trans-venous occlusion of incompetent pelvic veins for chronic pelvic pain in
      women: a systematic review.
AB  - Chronic pelvic pain (CPP) affects 24% of women worldwide; the cause cannot be
      identified in 40% despite invasive investigations. Dilated, refluxing pelvic
      veins may be a cause of CPP and treatment by trans-venous occlusion is
      increasingly performed when gynecological causes are excluded, but is it
      effective? A systematic review of the literature published between 1966 and July
      2014 was conducted. Two authors independently reviewed potential studies
      according to a set of eligibility criteria, with a third assessor available as an
      arbiter. Thirteen studies including 866 women undergoing trans-venous occlusion
      of pelvic veins for CPP were identified (Level of evidence: one study grade 2b,
      12 studies grade four). Statistical significant improvements in pelvic pain were
      reported in nine of the 13 studies. Technical success was reported in 865 of 866
      (99.8%) with low complication rates: coil migration in 14 women (1.6%), abdominal
      pain in ten women (1.2%) and vein perforation in five (0.6%). In a study on
      varicose veins of the legs, recurrence was seen in 13% of 179 women 5-years
      following coil embolization. Subjective improvements in pain were seen in all 13
      studies after treatment by trans-venous occlusion. All 13 studies were of poor
      methodological quality. Complication rates were low and no fatalities occurred.
      Well-designed studies are essential to determine whether pelvic vein incompetence
      (PVI) is associated with CPP, and to explore whether trans-venous occlusion of
      PVI improves quality of life for these women. 

PMID- 25590500
TI  - Achieving an early pregnancy following allogeneic uterine transplantation in a
      rabbit model.
AB  - OBJECTIVE: Uterine transplantation (UTx) has been proposed as a treatment option
      for women diagnosed with absolute uterine factor infertility (AUFI). The goal of
      UTx remains achieving pregnancy and live birth of a healthy neonate following
      allogeneic UTx. Our aim was to assess whether fertility was possible following
      allogeneic uterine transplantation (UTx), when the recipient had demonstrated
      long-term survival and had been administered immunosuppression. STUDY DESIGN:
      Nine allogeneic UTx in New Zealand White rabbits were performed using a pre
      determined protocol. Tacrolimus was the immunosuppressant selected. Embryos were
      transferred into both cornua of the sole living recipient via a mini-midline
      laparotomy. The pregnancy was monitored with regular reproductive profiles and
      serial trans-abdominal ultrasound to measure conceptus growth (gestation sac and
      crown rump length (CRL)). RESULTS: In the sole surviving doe a gestation sac was
      visualised on ultrasound from Day 9 (D9) after embryo transfer. Gestation sac
      diameter and CRL increased from D9 to D16 but by D18 the gestation sac had
      reduced in size. The fetus was no longer visible, suggesting fetal resorption had
      occurred. Subsequent scans on D22 and D25 did not demonstrate a gestation sac.
      Scheduled necropsy on D27 and histopathology confirmed evidence of a gravid
      uterus and presence of a gestational sac. A single episode of acute rejection
      occurred on D13. CONCLUSION: Pregnancy was achieved after rabbit allogeneic UTx
      but serial ultrasound suggested that fetal demise occurred prior to scheduled
      necropsy. The study represents only the third example of conception and pregnancy
      following an animal allogeneic UTx.

PMID- 25590501
TI  - Effect of maternal death reviews and training on maternal mortality among
      cesarean delivery: post-hoc analysis of a cluster-randomized controlled trial.
AB  - OBJECTIVES: To explore the differential effect of a multifaceted intervention on
      hospital-based maternal mortality between patients with cesarean and vaginal
      delivery in low-resource settings. STUDY DESIGN: We reanalyzed the data from a
      major cluster-randomized controlled trial, QUARITE (Quality of care, Risk
      management and technology in obstetrics). These subgroup analyses were not pre
      specified and were treated as exploratory. The intervention consisted of an
      initial interactive workshop and quarterly educational clinically oriented and
      evidence-based outreach visits focused on maternal death reviews (MDR) and best
      practices implementation. The trial originally recruited 191,167 patients who
      delivered in each of the 46 participating hospitals in Mali and Senegal, between
      2007 and 2011. The primary endpoint was hospital-based maternal mortality.
      Subgroup-specific Odds Ratios (ORs) of maternal mortality were computed and
      tested for differential intervention effect using generalized linear mixed model
      between two subgroups (cesarean: 40,975; and vaginal delivery: 150,192). RESULTS:
      The test for homogeneity of intervention effects on hospital-based maternal
      mortality among the two delivery mode subgroups was statistically significant (p
      value: 0.0201). Compared to the control, the adjusted OR of maternal mortality
      was 0.71 (95% CI: 0.58-0.82, p=0.0034) among women with cesarean delivery. The
      intervention had no significant effect among women with vaginal delivery
      (adjusted OR 0.87, 95% CI 0.69-1.11, p=0.6213). This differential effect was
      particularly marked for district hospitals. CONCLUSION: Maternal deaths reviews
      and on-site training on emergency obstetric care may be more effective in
      reducing maternal mortality among high-risk women who need a cesarean section
      than among low-risk women with vaginal delivery.

PMID- 25590502
TI  - Distribution of sagittal occlusal relationships in different stages of dentition.
AB  - The aim of this study was to assess the distribution of sagittal occlusal
      relationships in different dentition periods in a Turkish sample group. In total,
      1,110 patients (561 females, 549 males) aged 4.6-23 years were randomly chosen
      after intraoral clinical examination. The subjects were classified according to
      their sagittal occlusal relationships and four dentition stages -deciduous, early
      mixed, late mixed, and permanent dentition. The statistical significance of the
      occurrence of malocclusion types in dentition stages was evaluated by Chi-square
      and Fischer's exact tests. Class I malocclusion was observed at the highest rate
      in all dentition stages. Class III malocclusion was observed at the highest rate
      in the permanent dentition, whereas Class II malocclusion was observed at the
      highest rate in the late mixed dentition. The rates of Class I, II, and III
      malocclusions were similar in males and females. Our study reveals that the
      prevalence of malocclusion and need for orthodontic treatment has increased in
      the population towards the permanent dentition. 

PMID- 25590503
TI  - Dental fluorosis and its influence on children's life.
AB  - This study verified the prevalence of dental fluorosis in 12-year-old children
      and its association with different fluoride levels in the public water supply,
      and evaluated the level of perception of dental fluorosis by the studied
      children. To assess fluorosis prevalence, clinical examinations were performed
      and a structured instrument was used to evaluate the self-perception of
      fluorosis. The water supply source in the children's area of residence since
      birth was used as the study criterion. In total, 496 children were included in
      the study. Fluorosis was diagnosed in 292 (58.9%) children; from these, 220
      (44.4%) children were diagnosed with very mild fluorosis, 59 (11.9%) with mild
      fluorosis, 12 (2.4%) with moderate fluorosis, and 1 (0.2%) child with severe
      fluorosis. A significant association (p = 0.0004) was observed between the
      presence of fluorosis and areas with excessive fluoride in the water supply.
      Among the 292 children that showed fluorosis, 40% perceived the presence of spots
      in their teeth. The prevalence of fluorosis was slightly high, and the mildest
      levels were the most frequently observed. Although most of the children showed
      fluorosis to various degrees, the majority did not perceive these spots,
      suggesting that this alteration did not affect their quality of life. 

PMID- 25590504
TI  - Dental age estimation in a Brazilian adult population using Cameriere's method.
AB  - The objectives of this study were to develop a specific formula to estimate age
      in a Brazilian adult population and to compare the original formula from
      Cameriere to this Brazilian formula. The sample comprised 1,772 periapical
      radiographs from 443 subjects (219 men, 224 women) that were organized into 12
      groups according to sex (men or women) and age (20-29, 30-39, 40-49, 50-59, 60
      69, and 70 years and older). The films were analyzed using the criteria described
      by Cameriere et al. (2004) and Adobe Photoshop(r). We obtained a mean error of
      8.56 (SD = 5.80) years for tooth 13, 7.99 (SD = 5.78) years for tooth 23, 8.38
      (SD = 6.26) years for tooth 33, and 8.20 (SD = 6.54) years for tooth 43. When
      teeth were combined in the analysis, we observed lower mean errors. The Brazilian
      formula developed from this sample group was more accurate than Cameriere's
      formula. However, other factors must be considered to improve age estimates in
      adults.

PMID- 25590505
TI  - Chronicity factors of temporomandibular disorders: a critical review of the
      literature.
AB  - Facial pain often persists long after any identifiable organic pathology has
      healed. Moreover, in a subgroup of patients with temporomandibular disorder
      (TMD), no treatment is effective. Knowledge of factors associated with persistent
      pain in TMD could help identify personalized treatment approaches. Therefore, we
      conducted a critical review of the literature for the period from January 2000 to
      December 2013 to identify factors related to TMD development and persistence. The
      literature findings showed that chronic TMD is marked by psychological distress
      (somatization and depression, affective distress, fear of pain, fear of movement,
      and catastrophizing) and characteristics of pain amplification (hyperalgesia and
      allodynia). Furthermore, these factors seem to interact in TMD development. In
      addition, our review demonstrates that upregulation of the serotonergic pathway,
      sleep problems, and gene polymorphisms influence the chronicity of TMD. We
      conclude that psychological distress and pain amplification contribute to chronic
      TMD development, and that interactions among these factors complicate pain
      management. These findings emphasize the importance of multidisciplinary
      assistance in TMD treatment. 

PMID- 25590506
TI  - CBCT-based evaluation of integrity of cortical sinus close to periapical lesions.
AB  - The purpose of the present study was to test the applicability of cone beam
      computed tomography (CBCT) to evaluate the integrity of the cortical sinus close
      to periapical lesions. Two observers analyzed samples of 64 alveoli of first
      molar roots in macerated swine maxillas prepared with perchloric acid to simulate
      periapical lesions. The specimens were evaluated using CBCT (55-mm high and 100
      mm diameter cylinder at 0.2-mm voxel resolution) for the presence of oroantral
      communication (OAC) caused by the simulated lesions. Sensitivity, specificity,
      and accuracy were calculated. Fair values were obtained for accuracy (66%-78%)
      and good values for specificity (70%-98%), whereas the values for sensibility
      showed relevant variation (41%-78%). For this reason, the interobserver agreement
      score was weak. CBCT proved capable of evaluating the integrity of the cortical
      sinus (absence of oroantral communication) when it lies close to an apical
      periodontitis lesion. However, the low interobserver agreement reflects the
      difficulty in performing diagnoses when OAC is adjacent to a periapical lesion,
      using the acquisition protocol adopted in this research. This could be attributed
      to the high level of image noise.

PMID- 25590507
TI  - Genotoxic potential of 10% and 16% carbamide peroxide in dental bleaching.
AB  - Dental bleaching has become one of the most frequently requested esthetic
      treatments in dental offices. Despite the high clinical success observed with
      this procedure, some adverse effects have been reported, including a potential
      for developing premalignant lesions, root resorption and tooth sensitivity,
      especially when misused. The aim of this study was to evaluate the genotoxic
      response using a micronucleus (MN) assay, after the application of two
      concentrations of carbamide peroxide. Thirty-seven patients were divided into two
      groups and randomly received either a 10% carbamide peroxide (CP) (19) or a 16%
      carbamide peroxide (18) concentration for 21 days in individual dental trays.
      Gingival margin cells were collected immediately before the first use (baseline),
      and then 15 and 45 days after baseline. The cells were placed on a histological
      slide, stained by the Feulgen technique, and evaluated by an experienced blinded
      examiner. One thousand cells per slide were counted, and the MN rate was
      determined. The two groups were analyzed by the Wilcoxon rank-sum test and the
      Kruskal-Wallis equality-of-populations rank test. A slight increase in MN was
      observed for both groups, in comparison with the baseline, at 15 days. However,
      no difference was observed between the two groups (10% and 16%), at either 15 or
      45 days (p = 0.90). When bleaching is not prolonged or not performed very
      frequently, bleaching agents containing carbamide peroxide alone will not cause
      mutagenic stress on gingival epithelial cells. 

PMID- 25590508
TI  - Comparison surface characteristics and chemical composition of conventional
      metallic and nickel-free brackets.
AB  - This study aims at comparing conventional and nickel-free metal bracket surface
      characteristics with elemental composition by scanning electron microscopy (SEM),
      using energy dispersive spectroscopy (EDS). The sample consisted of 40 lower
      incisor brackets divided into four groups: ABZ = conventional brackets, Kirium
      Abzil 3M(r) (n = 10); RL = conventional brackets, Roth Light Morelli(r) (n = 10);
      NF = nickel-free brackets, Nickel-Free Morelli(r) (n = 10); and RM = nickel-free
      brackets, Roth Max Morelli(r) (n = 10). Qualitative evaluation of the bracket
      surface was performed using SEM, whereby surface features were described and
      compared. The elemental composition was analyzed by EDS. According to surface
      analysis, groups ABZ and RL showed a homogeneous surface, with better finishing,
      whereas the surfaces in groups NF and RM were rougher. The chemical components
      with the highest percentage were Fe, Cr and C. Groups NF and MR showed no nickel
      in their composition. In conclusion, the bracket surface of the ABZ and RL groups
      was more homogeneous, with grooves and pores, whereas the surfaces in groups NF
      and RM showed numerous flaws, cracks, pores and grooves. The chemical composition
      analysis confirmed that the nickel-free brackets had no Ni in their composition,
      as confirmed by the manufacturer's specifications, and were therefore safe to use
      in patients with a medical history of allergy to this metal.

PMID- 25590509
TI  - Presumptive intramuscular hemangioma of the masseter muscle.
AB  - BACKGROUND: Hemangioma is a benign vascular proliferation. Intramuscular
      hemangiomas are rare, accounting for less than 1% of all hemangiomas, and occur
      normally in the trunk and extremities. Approximately 10-20% of intramuscular
      hemangiomas are found in the head and neck region, most often in the masseter
      muscles. The typical clinical characteristic is a painful soft tissue mass
      without cutaneous changes. Currently, MRI is the standard imaging technique for
      diagnosing soft-tissue hemangioma. The optimal management is the surgical
      resection. CASE REPORT: We report a case of 34-year-old male patient consulted
      for a swelling of 1 year evolution, around the parotid region. On physical
      examination, a soft, well-contoured lesion of about 2 cm on its long axis was
      found. MRI showed a space-occupying lesion in the left masseter muscle, with
      intermediate signal intensity on T1-weighted images and hyperignal intensity on
      T2-weighted images, containing nodular hypointense foci corresponding to
      calcification. The presumptive diagnosis of an intramasseteric hemangioma with
      phlebolith was made based on these findings. The patient was informed about her
      condition, and treatment options were discussed; however, the patient elected to
      forgo treatment at that time. CONCLUSIONS: The possibility of an IMH should be
      included in the differential diagnosis of any intra-masseteric lesion. The
      appropriate radiologic examinations especially MRI can enhance accurate
      preoperative diagnosis; the treatment of choice should be individualized in view
      of the clinical status of the patient.

PMID- 25590510
TI  - Changes in physicochemical and transport properties of a reverse osmosis membrane
      exposed to chloraminated seawater.
AB  - This study contributed to improving our understanding of how disinfectants,
      applied to control biofouling of reverse osmosis (RO) membranes, result in
      membrane performance degradation. We investigated changes in physicochemical
      properties and permeation performance of a RO membrane with fully aromatic
      polyamide (PA) active layer. Membrane samples were exposed to varying
      concentrations of monochloramine, bromide, and iodide in both synthetic and
      natural seawater. Elemental analysis of the membrane active layer by Rutherford
      backscattering spectrometry (RBS) revealed the incorporation of bromine and
      iodine into the polyamide. The kinetics of polyamide bromination were first order
      with respect to the concentration of the secondary oxidizing agent Br2 for the
      conditions investigated. Halogenated membranes were characterized after treatment
      with a reducing agent and heavy ion probes to reveal the occurrence of
      irreversible ring halogenation and an increase in carboxylic groups, the latter
      produced as a result of amide bond cleavage. Finally, permeation experiments
      revealed increases in both water permeability and salt passage as a result of
      oxidative damage. 

PMID- 25590511
TI  - Completeness and accuracy of the wisconsin immunization registry: an evaluation
      coinciding with the beginning of meaningful use.
AB  - CONTEXT: Vaccination coverage rates can be improved through the application of
      complete and accurate immunization information systems (IISs). OBJECTIVE:
      Evaluate the completeness and accuracy of Wisconsin's IIS, the Wisconsin
      Immunization Registry (WIR). DESIGN: Cross-sectional evaluation, comparing
      vaccination medical records (MRs) from provider clinics with WIR records.
      PARTICIPANTS: Medical records of patients born during 2009 were randomly selected
      from 251 Wisconsin clinics associated with the Vaccines for Children Program.
      MAIN OUTCOME MEASURES: Completeness: percentage of patients with client records
      in the WIR, percentage of patients up-to-date (%UTD) with the 4:3:1:3:3:1:4
      vaccination series, and percentage of patients' MR vaccinations matched by
      administration date (+/-10 days) and type to vaccinations documented in the WIR.
      Accuracy: percentages of matched vaccinations with the same administration date,
      same trade name (TN), and same lot number. RESULTS: Of the 1863 selected patient
      MRs, 98% (n = 1833) had WIR client records and 97% of their 30 899 vaccinations
      were documented in the WIR. The %UTD was 49.3% using the MR only, 76.5% using the
      WIR only, and 75.2% as estimated by the National Immunization Survey. Among
      matched vaccinations, 99% had the same administration date, 96% had the same TN,
      and 95% had the same lot number. Compared with patients from clinics that entered
      data into the WIR using data exchange from electronic health records, patients
      from clinics that entered data using the Web-based user interface were less
      likely to have client records in the WIR (odds ratio: 0.3; 95% confidence
      interval: 0.1-0.9) and less likely to have accurate TNs (odds ratio: 0.3; 95%
      confidence interval: 0.1-0.5). CONCLUSIONS: The WIR was complete and accurate
      among this sample of children born during 2009 and provided a vaccination
      coverage assessment similar to the National Immunization Survey. Our results
      provide support for the expectation that meaningful use and other initiatives
      that increase data exchange from electronic health records to IISs will improve
      IIS data quality.

PMID- 25590512
TI  - Humic acid and glucan: protection against liver injury induced by carbon
      tetrachloride.
AB  - Humic acids (HAs) have a rather pleiotropic presence, however, their biological
      effects are still unclear. In this study, we focused on possible hepatoprotective
      effects of either HA alone or in combination with beta-glucan. Using a model of
      experimental hepatotoxicity caused by carbon tetrachloride (CCL4), we showed that
      both HA and the glucan-HA combination offered significant protection against
      hepatotoxicity, with the combination offering superior effects. Our biochemical
      observations were confirmed by histological evaluation. Based on the experimental
      data, we conclude that whereas HA has significant effects, the synergy with
      glucan offers superior effects. 

PMID- 25590513
TI  - Generation of Reactive Oxygen Species Mediated by  1-Hydroxyphenazine, a
      Virulence Factor of Pseudomonas aeruginosa.
AB  - 1-Hydroxyphenazine (1-HP) is a virulence factor produced by Pseudomonas
      aeruginosa. In this study,supercoiled plasmid DNA was employed as an analytical
      tool for the detection of ROS generation mediated by 1-HP. These assays provided
      evidence that 1-HP, in conjunction with NADPH alone or NADPH and the enzyme
      NADPH:cytochrome P450 reductase, mediated the production of superoxide radical
      under physiological conditions. Experiments with murine macrophage RAW264.7 cells
      and profluorescent ROS probes dichlorodihydrofluorescein or dihydroethidine
      provided preliminary evidence that 1-HP mediates the generation of intracellular
      oxidants. Generation of reactive oxygen species may contribute to the virulence
      properties of 1-HP in P. aeruginosa infections.

PMID- 25590514
TI  - State laws, syringe exchange, and HIV among persons who inject drugs in the
      United States: History and effectiveness.
AB  - In 1981, when acquired immune deficiency syndrome (AIDS) was first observed among
      persons who inject drugs, almost all US states had laws criminalizing the
      possession and distribution of needles and syringes for injecting illicit drugs.
      We reviewed changes to these laws to permit 'syringe exchanges' and the provision
      of public funding for such programs. Most of the changes in law occurred during
      the 1990s, 5-10 years later than in many other countries. Public funding of
      syringe exchanges is associated with lower rates of human immunodeficiency virus
      (HIV) infection, greater numbers of syringes distributed (a possible causal
      mechanism), and greater numbers of health and social services provided.
      Experience in the United states may prove useful in other countries: state,
      provincial, and local governments may need to move ahead of central governments
      in addressing HIV infection among persons who inject drugs. 

PMID- 25590516
TI  - Targeting cell death pathways with small molecules: playing with life and death
      at the cellular level to treat diseases.

PMID- 25590515
TI  - Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as
      potential therapeutic agents for the treatment of Huntington's disease.
AB  - We report on the development of a series of pyrimidine carboxylic acids that are
      potent and selective inhibitors of kynurenine monooxygenase and competitive for
      kynurenine. We describe the SAR for this novel series and report on their
      inhibition of KMO activity in biochemical and cellular assays and their
      selectivity against other kynurenine pathway enzymes. We describe the
      optimization process that led to the identification of a program lead compound
      with a suitable ADME/PK profile for therapeutic development. We demonstrate that
      systemic inhibition of KMO in vivo with this lead compound provides
      pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in
      the periphery and in the central nervous system. 

PMID- 25590517
TI  - Laryngeal electromyography-guided hyaluronic acid vocal fold injection for
      unilateral vocal fold paralysis: a prospective long-term follow-up outcome
      report.
AB  - IMPORTANCE: Unilateral vocal fold paralysis (UVFP) is a common voice disorder
      that may cause glottal closure insufficiency with hoarseness of voice. Laryngeal
      electromyography (LEMG)-guided hyaluronic acid vocal fold (VF) injection has been
      proposed as a treatment option to improve glottal closure with a satisfactory
      short-term effect. To our knowledge, this study reports the first long-term
      follow-up result of this treatment modality. OBJECTIVE: To present the long-term
      treatment results of LEMG-guided hyaluronic acid VF injection for UVFP. DESIGN,
      SETTING, AND PARTICIPANTS: Prospective study of the treatment results of 74
      patients who received LEMG-guided hyaluronic acid VF injection for UVFP at a
      tertiary referral medical center from March 2010 to February 2013. INTERVENTIONS:
      In the office-based procedure, 1.0 mL of hyaluronic acid was injected via a 26
      gauge monopolar injectable needle electrode into paralyzed thyroarytenoid muscles
      by LEMG guidance. MAIN OUTCOMES AND MEASURES: Various glottal closure evaluations
      such as normalized glottal gap area, maximal phonation time, phonation quotient,
      mean airflow rate, perceptual GRBAS (grade, roughness, breathiness, asthenia,
      strain) scale, and Voice Handicap Index were compared before and after injection
      using the nonparametric Wilcoxon signed rank test within 1 month, at 6 months,
      and at the last follow-up examination. RESULTS: Sixty patients had been followed
      up for at least 6 months. Forty-four patients received only 1 injection, and 16
      patients received repeated injections (2 injections for 13 patients and 3 for 3
      patients). All the glottal closure parameters improved significantly (P < .001)
      within 1 month, at 6 months, and at the last follow-up examination, with a mean
      (SD) of 17.4 (8.9) months. At the last follow-up examination, the mean (SD)
      normalized glottal gap area was significantly reduced from 7.9 (5.7) to 0.6
      (1.6). Mean (SD) maximal phonation time was significantly prolonged from 4.6
      (3.8) seconds to 12.1 (7.4) seconds. Mean (SD) phonation quotient was
      significantly reduced from 647 (508) mL/s to 277 (212) mL/s. Mean (SD) airflow
      rate was significantly reduced from 445 (338) mL/s to 175 (145) mL/s. When all
      the GRBAS scale parameters improved, the mean (SD) Voice Handicap Index score was
      significantly reduced from 76 (22) to 38 (30) (all P < .001). CONCLUSIONS AND
      RELEVANCE: Of the 74 patients in this study, 44 (60%) who received a single
      injection and 16 (22%) who received repeated injections did not require another
      treatment after long-term follow-up. Laryngeal electromyography-guided hyaluronic
      acid VF injection is an option for treating UVFP with satisfactory results.

PMID- 25590518
TI  - Nonfunctional Pancreatic Neuroendocrine Tumors: Advances in Diagnosis,
      Management, and Controversies.
AB  - In this article, we aimed to review the literature on the clinics and management
      of nonfunctional pancreatic neuroendocrine tumors (NPNET). Pancreatic
      neuroendocrine tumors (PNET) are rare tumors with a <1/100,000 incidence and
      constitute approximately 2 to 10% of all pancreatic tumors. Nonfunctional PNETs
      are difficult to detect at early stages since they have no symptoms. Except those
      detected accidentally during different diagnoses, the majority of PNETs are
      detected in the advanced stages, with symptoms related to tumor size or liver
      metastasis. We reviewed the studies published in the English medical literature
      through PubMed and summarized the clinical features and current approaches to the
      treatment and follow-up of the NPNET. The common imaging techniques used for the
      detection of tumor localization, size, locoregional, and metastatic involvement
      are contrasted computed tomography, magnetic resonance imaging, endoscopic
      ultrasonography, and somatostatin receptor scintigraphy. Surgical resection is
      the only curative treatment. However, in advanced locoregional disease and liver
      metastasis, interventive ablative therapies such as palliative reductive surgery,
      selective hepatic arterial embolization, radiofrequency ablation; and systemic
      therapies, such as peptide receptor radionuclide therapy, chemotherapy,
      somatostatin analogous therapy, interferon, VEGF inhibitor, and mTOR inhibitor
      may be used as symptom relieving or may improve progression-free survival and
      total survival. Current knowledge on NPNET shows that the treatment should be
      personalized considering the prognostic features and life expectancy of the
      patient. 

PMID- 25590519
TI  - Differences in the location of guest molecules within zeolite pores as revealed
      by multilaser excitation confocal fluorescence microscopy: which molecule is
      where?
AB  - A detailed and systematic polarized confocal fluorescence microscopy
      investigation is presented on three batches of large coffin-shaped ZSM-5 crystals
      (i.e., parent, steamed at 500  degrees C, and steamed at 700  degrees C). In
      total, six laser lines of different wavelength in the visible region are employed
      on two crystal positions and three orientations with respect to the polarization
      plane of the excitation laser light. A fluorescent probe molecule is generated
      inside the zeolite pores, originating from the acid-catalyzed oligomerization of
      4-fluorostyrene. A thorough analysis of the polarization plane of emitting
      fluorescent light reveals insight into the orientation of the fluorescent probe
      molecule restricted by the highly ordered zeolite channel framework, thereby
      visualizing pore accessibility and clearly distinguishing the occupation of
      straight and sinusoidal channels by the probe molecule. Spectral features are,
      furthermore, observed to tell apart molecules situated in one or the other pore.
      Special focus was given on the rim and tip regions of the zeolite ZSM-5 crystals.
      On the basis of the confocal approach of the investigation, the aforementioned
      features are evaluated in three dimensions, while the degradation of the zeolite
      framework upon postsynthesis steam treatment could be visualized by occupation of
      the sinusoidal pores. 

PMID- 25590521
TI  - Hemostasis and thrombosis in major liver resection.
AB  - The liver plays an important role in the balance between hemostasis and
      thrombosis. Hepatic resection, particularly when performed in the presence of
      underlying parenchymal liver disease, can cause perturbation of this balance.
      This review summarizes the changes that occur in normal hemostasis and thrombosis
      before, during, and after nontransplant hepatic resection and, wherever possible,
      provides strategies for the perioperative management of bleeding and thrombosis. 

PMID- 25590520
TI  - Evolutionarily conserved pressure for the existence of distinct G2/M cell cycle
      arrest and A3H inactivation functions in HIV-1 Vif.
AB  - HIV-1 Vif assembles the Cul5-EloB/C E3 ubiquitin ligase to induce proteasomal
      degradation of the cellular antiviral APOBEC3 proteins. Detailed structural
      studies have confirmed critical functional domains in Vif that we have previously
      identified as important for the interaction of EloB/C, Cul5, and CBFbeta.
      However, the mechanism by which Vif recognizes substrates remains poorly
      understood. Specific regions of Vif have been identified as being responsible for
      binding and depleting APOBEC3G and APOBEC3F. Interestingly, we have now
      identified distinct yet overlapping domains that are required for HIV-1 Vif
      mediated G2/M-phase cell cycle arrest and APOBEC3H degradation, but not for the
      inactivation of APOBEC3G or APOBEC3F. Surprisingly, Vif molecules from primary
      HIV-1 variants that caused G2/M arrest were unable to inactivate APOBEC3H; on the
      other hand, HIV-1 Vif variants that could inactivate APOBEC3H were unable to
      induce G2/M arrest. All of these Vif variants still maintained the ability to
      inactivate APOBEC3G/F. Thus, primary HIV-1 variants have evolved to possess
      distinct functional activities that allow them to suppress APOBEC3H or cause G2
      cell cycle arrest, using mutually exclusive interface domains. APOBEC3H depletion
      and G2 arrest are apparently evolutionary selected features that cannot co-exist
      on a single Vif molecule. The existence and persistence of both types of HIV-1
      Vif variant suggests the importance of APOBEC3H suppression and cell cycle
      regulation for HIV-1's survival in vivo.

PMID- 25590522
TI  - Fibrinogen level deteriorates before other routine coagulation parameters and
      massive transfusion in the early phase of severe trauma: a retrospective
      observational study.
AB  - In trauma, hemostatic functions should be maintained appropriately to prevent
      massive bleeding. This study elucidated the time-dependent changes in platelet
      count and coagulation variables, and the effects of disseminated intravascular
      coagulation (DIC) on these changes during the early phase of trauma. Trauma
      patients with an injury severity score >=16 were enrolled. The critical levels of
      platelet count and coagulation variables were defined according to recent trauma
      guidelines. Massive transfusion was defined as >10 units red cell concentrate.
      The time from arrival at the emergency department to reaching the critical levels
      and meeting the criteria for massive transfusion were evaluated. Eighty trauma
      patients were enrolled; 35 were diagnosed with DIC on arrival. Among all
      patients, fibrinogen levels reached the critical level earliest among routine
      coagulation parameters; other routine coagulation parameters deteriorated after
      the patients met the criteria for massive transfusion. Routine coagulation
      parameters reached their critical levels earlier in DIC patients than patients
      without DIC. Massive transfusion was performed more frequently in DIC patients,
      who met the criteria earlier. During the early phase of trauma, fibrinogen levels
      deteriorate earlier than other routine coagulation parameters, especially in DIC
      patients. 

PMID- 25590524
TI  - Coagulation in patients with severe sepsis.
AB  - In the majority of patients with severe sepsis, systemic activation of
      coagulation is present. Increasing evidence points to an extensive cross-talk
      between coagulation and inflammation that may play an important role in the
      pathogenesis of sepsis. Inflammation not only leads to activation of coagulation,
      but coagulation also considerably affects inflammatory activity. Molecular
      pathways that contribute to inflammation-induced activation of coagulation have
      been precisely identified. Proinflammatory cytokines and other mediators are
      capable of activating the coagulation system and downregulating important
      physiological anticoagulant pathways. Activation of the coagulation system and
      ensuing thrombin generation is dependent on expression of tissue factor on
      activated mononuclear cells and endothelial cells, and is insufficiently
      counteracted by TFPI. Simultaneously, endothelial-bound anticoagulant mechanism,
      in particular the protein C system, is shutoff by proinflammatory cytokines. In
      addition, fibrin removal is severely inhibited, because of inactivation of the
      fibrinolytic system, caused by an upregulation of its main inhibitor, plasminogen
      activator inhibitor type 1 (PAI-1). Increased fibrin formation and impaired
      removal lead to (micro)vascular thrombosis, which may result in tissue ischemia
      and subsequent organ damage. The cornerstone of the management of coagulation in
      sepsis is the specific and vigorous treatment of the underlying disorder.
      Strategies aimed at the inhibition of coagulation activation may theoretically be
      justified and have been found beneficial in experimental and initial clinical
      studies. Heparin may be an effective anticoagulant approach and alternative
      strategies comprise restoration of physiological anticoagulant pathways. 

PMID- 25590525
TI  - Hypercoagulability and venous thromboembolism in burn patients.
AB  - To our knowledge, this is the first comprehensive review on the subject of venous
      thromboembolism (VTE) and hypercoagulability in burn patients. Specific changes
      in coagulability are reviewed using data from thromboelastography and other
      techniques. Disseminated intravascular coagulation in burn patients is discussed.
      The incidence and risk factors associated with VTE in burn patients are then
      examined, followed by the use of low-molecular-weight heparin thromboprophylaxis
      and monitoring techniques using antifactor Xa levels. The need for large,
      prospective trials in burn patients is highlighted, especially in the areas of
      VTE incidence and safe, effective thromboprophylaxis. 

PMID- 25590526
TI  - Hemostasis and thrombosis in continuous renal replacement treatment.
AB  - During continuous renal replacement therapy, the delicate equilibrium of
      hemostasis is disturbed. Owing to a complex interaction of critical illness,
      uremia, use of an extracorporeal circuit and anticoagulation, patients exhibit
      both hypercoagulability and an increased risk of bleeding. Contact of blood with
      foreign material initiates coagulation by triggering the contact activation
      coagulation pathway, the tissue factor-factor VIIa pathway and activation of
      platelets and monocytes, which adhere to the membrane. The interaction with
      critical illness induced alterations further enhances coagulation and
      inflammation. Classical markers of coagulation, prothrombin and activated
      thromboplastin time, and platelet count do not detect the procoagulant state.
      Critically ill patients also have in increased risk of bleeding and
      anticoagulation used for circuit clotting enhances this risk. Heparin is most
      commonly used. Heparin increases the risk of bleeding. Its efficacy and safety
      are further compromised by antithrombin deficiency, heparin binding to acute
      phase proteins and apoptotic and necrotic cells, and by its unpredictable effects
      on inflammation. Its interference with anticoagulation is therefore unreliable
      during critical illness. Citrate provides regional anticoagulation and increases
      biocompatibility. It is better tolerated than heparin and confers less bleeding,
      less transfusion, and longer circuit life. 

PMID- 25590523
TI  - Profound endothelial damage predicts impending organ failure and death in sepsis.
AB  - Endothelial damage contributes to organ failure and mortality in sepsis, but the
      extent of the contribution remains poorly quantified. Here, we examine the
      association between biomarkers of superficial and profound endothelial damage
      (syndecan-1 and soluble thrombomodulin [sTM], respectively), organ failure, and
      death in sepsis. The data from a clinical trial, including critically ill
      patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were
      studied. Syndecan-1 and sTM levels at the time of study enrollment were
      determined. The predictive ability of biomarker levels on death and organ
      failures during follow-up were assessed in Cox models adjusted for potential
      confounders including key organ dysfunction measures assessed at enrollment. Of
      the 1,103 included patients, 418 died. sTM levels at the time of enrollment
      independently predicted risk of death in adjusted models (hazard ratio [HR]
      [highest quartile > 14 ng/mL vs. lowest quartile < 7 ng/mL] 2.2 [95% confidence
      interval [CI]: 1.2-4.0], p = 0.02, respectively). Conversely, syndecan-1 levels
      failed to predict death (adjusted HR [> 240 vs. < 70 ng/mL] 1.0 [95% CI: 0.6
      1.5], p = 0.67). sTM but not syndecan-1 levels at enrollment predicted risk of
      multiple organ failure during follow-up (HR [> 14 ng/mL vs. < 7 ng/mL] 3.5 [95%
      CI: 1.5-8.3], p = 0.005 and 2.0 [95% CI: 0.8-5.0], p = 0.1321, respectively).
      Profound damage to the endothelium independently predicts risk of multiple organ
      failure and death in septic patients. Our findings also suggest that the
      detrimental effect of profound endothelial damage on risk of death operates via
      mechanisms other than causing organ failures per se. Therefore, damage to the
      endothelium appears centrally involved in the pathogenesis of death in sepsis and
      could be a target for intervention. 

PMID- 25590527
TI  - Hemostatic and thrombotic issues in cardiac surgery.
AB  - Cardiac surgery with cardiopulmonary bypass determines a serious imbalance of the
      hemostatic system. The clinical pattern is multifactorial, involving patient
      related, drug-related, and surgery-related factors. As a result, the patient is
      prone to both hemorrhagic and thrombotic complications. To address the clinical
      management of a bleeding patient after cardiac surgery, avoiding empirical
      administration of drugs and blood derivates, it is mandatory to correctly
      identify the factor(s) responsible for bleeding. Bleeding after cardiac
      operations can be ascribed to seven basic mechanisms: residual heparin effect;
      reduced thrombin generation; fibrinogen deficiency; thrombocytopenia; platelet
      dysfunction; hyperfibrinolysis; and surgical sources. These factors may interact
      together, creating a complex coagulopathy. Point-of-care coagulation tests are
      useful to orienteer the clinician in this complex scenario. Viscoelastic
      coagulation tests find their greater usefulness in the diagnosis of the bleeding
      mechanism(s), whereas platelet function tests appear more useful for the
      preoperative assessment of patients under the effects of antiplatelet agents.
      Thromboembolic complications are the other side of the coin, and their prevention
      is still a matter of debate. Consumption of natural anticoagulants and
      endothelial disturbance are important mechanisms underlying this condition.
      Strategies to limit antithrombin (AT) consumption or to correct low postoperative
      levels of AT are still a matter of discussion. 

PMID- 25590528
TI  - Heparin-induced thrombocytopenia in critically ill patients.
AB  - Many critically ill patients receive heparin, either before intensive care unit
      (ICU) admission (e.g., postcardiac surgery), for prophylaxis/treatment of
      thrombosis, for hemodialysis/filtration, or even incidentally (e.g., flushing of
      intravascular catheters), and are therefore at risk for developing immune heparin
      induced thrombocytopenia (HIT), a prothrombotic drug reaction caused by platelet
      activating antiplatelet factor 4 (PF4)/heparin antibodies. However, HIT explains
      at most 1 in 100 thrombocytopenic ICU patients (HIT frequency 0.3-0.5% vs. 30-50%
      background frequency of ICU-associated thrombocytopenia), and most patients who
      form anti-PF4/heparin antibodies do not develop HIT; hence, HIT overdiagnosis
      often occurs. This review discusses HIT-related issues relevant to ICU patients,
      including how to (1) distinguish HIT both clinically and serologically from non
      HIT-related thrombocytopenia; (2) recognize HIT-mimicking disorders, such as the
      acute disseminated intravascular coagulation (DIC)/liver necrosis-limb necrosis
      syndrome; (3) prevent HIT in the ICU through use of low-molecular-weight heparin;
      and (4) treat HIT, including awareness of "PTT confounding" when anticoagulating
      patients with DIC. 

PMID- 25590529
TI  - Diterpene alkaloids with an aza-ent-kaurane skeleton from Isodon rubescens.
AB  - Two compounds belonging to a new group of diterpene alkaloids, kaurines A and B
      (1 and 2), and an alkaloid bearing a succinimide moiety (3) were obtained from
      Isodon rubescens. Their structures and absolute configurations were determined by
      spectroscopy and quantum-chemical computational (13)C NMR and ECD data analysis.
      These alkaloids differ from known diterpene alkaloids and diterpenoids and are
      presumably biosynthesized from ent-kaurane diterpenoids. 

PMID- 25590530
TI  - Composition and structural transitions of polyelectrolyte-surfactant complexes in
      the presence of fatty acid studied by NMR and cryo-SEM.
AB  - Insoluble complexes formed when a cationic polyelectrolyte is neutralized by the
      oppositely charged surfactant sodium dodecylethersulfate (SDES) in the presence
      and absence of lauric acid (LA) have been examined directly using NMR
      spectroscopy and cryo-SEM. Below the SDES critical micelle concentration (CMC')
      the insoluble complex contains about 10 times more water than just above CMC'.
      This is related to a structural transition of the complex, where water is
      contained mainly in larger compartments below CMC' and then mainly in narrower
      compartments above CMC'. The structure of the complex's solid matrix was
      monitored by recording two-dimensional T2-diffusion correlation spectra of the
      water proton resonance, which reveal the presence of several different water
      environments which correspond to different complex structures. Structural
      features in the micrometer range were confirmed using cryo-SEM. When LA is
      present, the larger water compartments seen below CMC' are to some extent present
      in the entire SDES concentration range, which is not the case in the absence of
      LA. Furthermore, the inclusion of LA into the SDES aggregates above CMC' leads to
      a lamellar sheetlike organization of the polyelectrolyte-stabilized surfactant
      phase. In the absence of LA, a stringy network of fibers is seen in cryo-SEM
      images, indicating a spherical or rodlike SDES phase. Consequently, the complex
      without LA holds about 1.7-1.9 times more water than the complex with LA above
      the SDES CMC'. T1 relaxation, (13)C chemical shifts, and (1)H resonance line
      widths of SDES in the system support the above observations. The combination of
      MAS NMR, T2-diffusion correlation, and cryo-SEM proved to be an effective method
      for studying structural transitions in the surfactant-polyelectrolyte(-LA)
      insoluble complexes. 

PMID- 25590531
TI  - Spectroscopy and viability of Bacillus subtilis spores after ultraviolet
      irradiation: implications for the detection of potential bacterial life on
      Europa.
AB  - One of the most habitable environments in the Solar System outside of Earth may
      exist underneath the ice on Europa. In the near future, our best chance to look
      for chemical signatures of a habitable environment (or life itself) will likely
      be at the inhospitable icy surface. Therefore, it is important to understand the
      ability of organic signatures of life and life itself to persist under simulated
      europan surface conditions. Toward that end, this work examined the UV photolysis
      of Bacillus subtilis spores and their chemical marker dipicolinic acid (DPA) at
      temperatures and pressures relevant to Europa. In addition, inactivation curves
      for the spores at 100 K, 100 K covered in one micron of ice, and 298 K were
      measured to determine the probability for spore survival at the surface. Fourier
      transform infrared spectra of irradiated DPA showed a loss of carboxyl groups to
      CO2 as expected but unexpectedly showed significant opening of the heterocyclic
      ring, even for wavelengths>200 nm. Both DPA and B. subtilis spores showed
      identical unknown spectral bands of photoproducts after irradiation, further
      highlighting the importance of DPA in the photochemistry of spores. Spore
      survival was enhanced at 100 K by ~5* relative to 298 K, but 99.9% of spores were
      still inactivated after the equivalent of ~25 h of exposure on the europan
      surface.

PMID- 25590532
TI  - Habitable evaporated cores: transforming mini-Neptunes into super-Earths in the
      habitable zones of M dwarfs.
AB  - We show that photoevaporation of small gaseous exoplanets ("mini-Neptunes") in
      the habitable zones of M dwarfs can remove several Earth masses of hydrogen and
      helium from these planets and transform them into potentially habitable worlds.
      We couple X-ray/extreme ultraviolet (XUV)-driven escape, thermal evolution, tidal
      evolution, and orbital migration to explore the types of systems that may harbor
      such "habitable evaporated cores" (HECs). We find that HECs are most likely to
      form from planets with ~1 M? solid cores with up to about 50% H/He by mass,
      though whether or not a given mini-Neptune forms a HEC is highly dependent on the
      early XUV evolution of the host star. As terrestrial planet formation around M
      dwarfs by accumulation of local material is likely to form planets that are small
      and dry, evaporation of small migrating mini-Neptunes could be one of the
      dominant formation mechanisms for volatile-rich Earths around these stars.

PMID- 25590534
TI  - Nonfaradaic nanoporous electrochemistry for conductometry at high electrolyte
      concentration.
AB  - Nanoporous electrified surfaces create a unique nonfaradaic electrochemical
      behavior that is sensitively influenced by pore size, morphology, ionic strength,
      and electric field modulation. Here, we report the contributions of ion
      concentration and applied ac frequency to the electrode impedance through an
      electrical double layer overlap and ion transport along the nanopores. Nanoporous
      Pt with uniform pore size and geometry (L2-ePt) responded more sensitively to
      conductivity changes in aqueous solutions than Pt black with poor uniformity
      despite similar real surface areas and enabled the previously difficult
      quantitative conductometry measurements at high electrolyte concentrations. The
      nanopores of L2-ePt were more effective in reducing the electrode impedance and
      exhibited superior linear responses to not only flat Pt but also Pt black,
      leading to successful conductometric detection in ion chromatography without ion
      suppressors and at high ionic strengths. 

PMID- 25590533
TI  - Identification of a fragment-like small molecule ligand for the methyl-lysine
      binding protein, 53BP1.
AB  - Improving our understanding of the role of chromatin regulators in the
      initiation, development, and suppression of cancer and other devastating diseases
      is critical, as they are integral players in regulating DNA integrity and gene
      expression. Developing small molecule inhibitors for this target class with
      cellular activity is a crucial step toward elucidating their specific functions.
      We specifically targeted the DNA damage response protein, 53BP1, which uses its
      tandem tudor domain to recognize histone H4 dimethylated on lysine 20 (H4K20me2),
      a modification related to double-strand DNA breaks. Through a cross-screening
      approach, we identified UNC2170 (1) as a micromolar ligand of 53BP1, which
      demonstrates at least 17-fold selectivity for 53BP1 as compared to other methyl
      lysine (Kme) binding proteins tested. Structural studies revealed that the tert
      butyl amine of UNC2170 anchors the compound in the methyl-lysine (Kme) binding
      pocket of 53BP1, making it competitive with endogenous Kme substrates. X-ray
      crystallography also demonstrated that UNC2170 binds at the interface of two
      tudor domains of a 53BP1 dimer. Importantly, this compound functions as a 53BP1
      antagonist in cellular lysates and shows cellular activity by suppressing class
      switch recombination, a process which requires a functional 53BP1 tudor domain.
      These results demonstrate that UNC2170 is a functionally active, fragment-like
      ligand for 53BP1. 

PMID- 25590536
TI  - Physiological recordings and RNA sequencing of the gustatory appendages of the
      yellow-fever mosquito Aedes aegypti.
AB  - Electrophysiological recording of action potentials from sensory neurons of
      mosquitoes provides investigators a glimpse into the chemical perception of these
      disease vectors. We have recently identified a bitter sensing neuron in the
      labellum of female Aedes aegypti that responds to DEET and other repellents, as
      well as bitter quinine, through direct electrophysiological investigation. These
      gustatory receptor neuron responses prompted our sequencing of total mRNA from
      both male and female labella and tarsi samples to elucidate the putative
      chemoreception genes expressed in these contact chemoreception tissues. Samples
      of tarsi were divided into pro-, meso- and metathoracic subtypes for both sexes.
      We then validated our dataset by conducting qRT-PCR on the same tissue samples
      and used statistical methods to compare results between the two methods. Studies
      addressing molecular function may now target specific genes to determine those
      involved in repellent perception by mosquitoes. These receptor pathways may be
      used to screen novel repellents towards disruption of host-seeking behavior to
      curb the spread of harmful viruses. 

PMID- 25590535
TI  - Structural characterization and in vivo evaluation of beta-Hairpin
      peptidomimetics as specific CXCR4 imaging agents.
AB  - The CXCR4 chemokine receptor is integral to several biological functions and
      plays a pivotal role in the pathophysiology of many diseases. As such, CXCR4 is
      an enticing target for the development of imaging and therapeutic agents. Here we
      report the evaluation of the POL3026 peptidomimetic template for the development
      of imaging agents that target CXCR4. Structural and conformational analyses of
      POL3026 and two of its conjugates, DOTA (POL-D) and PEG12-DOTA (POL-PD), by
      circular dichroism, two-dimensional NMR spectroscopy and molecular dynamics
      calculations are reported. In silico observations were experimentally verified
      with in vitro affinity assays and rationalized using crystal structure-based
      molecular modeling studies. [(111)In]-labeled DOTA conjugates were assessed in
      vivo for target specificity in CXCR4 expressing subcutaneous U87 tumors (U87-stb
      CXCR4) through single photon emission computed tomography (SPECT/CT) imaging and
      biodistribution studies. In silico and in vitro studies show that POL3026 and its
      conjugates demonstrate similar interactions with different micelles that mimic
      cellular membrane and that the epsilon-NH2 of lysine(7) is critical to maintain
      high affinity to CXCR4. Modification of this group with DOTA or PEG12-DOTA led to
      the decrease of IC50 value from 0.087 nM for POL3026 to 0.47 nM and 1.42 nM for
      POL-D and POL-PD, respectively. In spite of the decreased affinity toward CXCR4,
      [(111)In]POL-D and [(111)In]POL-PD demonstrated high and significant uptake in
      U87-stb-CXCR4 tumors compared to the control U87 tumors at 90 min and 24 h post
      injection. Uptake in U87-stb-CXCR4 tumors could be blocked by unlabeled POL3026,
      indicating specificity of the agents in vivo. These results suggest POL3026 as a
      promising template to develop new imaging agents that target CXCR4. 

PMID- 25590537
TI  - Advancing the climate data driven crop-modeling studies in the dry areas of
      Northern Syria and Lebanon: an important first step for assessing impact of
      future climate.
AB  - Inter-annual and seasonal variability in climatic parameters, most importantly
      rainfall, have potential to cause climate-induced risk in long-term crop
      production. Short-term field studies do not capture the full nature of such risk
      and the extent to which modifications to crop, soil and water management
      recommendations may be made to mitigate the extent of such risk. Crop modeling
      studies driven by long-term daily weather data can predict the impact of climate
      induced risk on crop growth and yield however, the availability of long-term
      daily weather data can present serious constraints to the use of crop models. To
      tackle this constraint, two weather generators namely, LARS-WG and MarkSim, were
      evaluated in order to assess their capabilities of reproducing frequency
      distributions, means, variances, dry spell and wet chains of observed daily
      precipitation, maximum and minimum temperature, and solar radiation for the eight
      locations across cropping areas of Northern Syria and Lebanon. Further, the
      application of generated long-term daily weather data, with both weather
      generators, in simulating barley growth and yield was also evaluated. We found
      that overall LARS-WG performed better than MarkSim in generating daily weather
      parameters and in 50 years continuous simulation of barley growth and yield. Our
      findings suggest that LARS-WG does not necessarily require long-term e.g., >30
      years observed weather data for calibration as generated results proved to be
      satisfactory with >10 years of observed data except in area with higher altitude.
      Evaluating these weather generators and the ability of generated weather data to
      perform long-term simulation of crop growth and yield is an important first step
      to assess the impact of future climate on yields, and to identify promising
      technologies to make agricultural systems more resilient in the given region.

PMID- 25590538
TI  - Experimental warming differentially affects microbial structure and activity in
      two contrasted moisture sites in a Sphagnum-dominated peatland.
AB  - Several studies on the impact of climate warming have indicated that peat
      decomposition/mineralization will be enhanced. Most of these studies deal with
      the impact of experimental warming during summer when prevalent abiotic
      conditions are favorable to decomposition. Here, we investigated the effect of
      experimental air warming by open-top chambers (OTCs) on water-extractable organic
      matter (WEOM), microbial biomasses and enzymatic activities in two contrasted
      moisture sites named Bog and Fen sites, the latter considered as the wetter ones.
      While no or few changes in peat temperature and water content appeared under the
      overall effect of OTCs, we observed that air warming smoothed water content
      differences and led to a decrease in mean peat temperature at the warmed Bog
      sites. This thermal discrepancy between the two sites led to contrasting changes
      in microbial structure and activities: a rise in hydrolytic activity at the
      warmed Bog sites and a relative enhancement of bacterial biomass at the warmed
      Fen sites. These features were not associated with any change in WEOM properties
      namely carbon and sugar contents and aromaticity, suggesting that air warming did
      not trigger any shift in OM decomposition. Using various tools, we show that the
      use of single indicators of OM decomposition can lead to fallacious conclusions.
      Lastly, these patterns may change seasonally as a consequence of complex
      interactions between groundwater level and air warming, suggesting the need to
      improve our knowledge using a high time-resolution approach. 

PMID- 25590539
TI  - Pooled versus separate tree-ring deltaD measurements, and implications for
      reconstruction of the Arctic Oscillation in northwestern China.
AB  - Stable hydrogen isotope ratios (deltaD) in tree rings are an attractive but still
      rarely explored terrestrial archive of past climatic information. Because the
      preparation of the cellulose nitrate for deltaD measurements requires more wood
      and a longer preparation time than preparation techniques for other isotopes in
      cellulose (delta18O or delta13C), it is challenging to obtain high-resolution
      records, especially for slow-growing trees at high elevations and in boreal
      regions. Here, we tested whether annually pooled samples of Qinghai spruce (Picea
      crassifolia Kom.) trees from northwestern China provided results similar to those
      derived as the mean of individual measurements of the same trees and whether the
      resulting chronologies recorded useful climate information. Inter-tree
      variability of deltaD was higher than that of measured ring width for the same
      trees. We found higher and significant coherence between pooled and mean isotope
      chronologies than that among the individual series. It showed a logarithmic
      relationship between ring mass and deltaD; however, accounting for the influence
      of ring mass on deltaD values only slightly improved the strength of climatic
      signals in the pooled records. Tree-ring deltaD was significantly positively
      correlated with the mean, maximum, and minimum temperatures during the previous
      winter and with maximum temperature during the current August, and significantly
      negatively correlated with precipitation in the previous November to January and
      the current July. The winter climate signal seems to dominate tree-ring deltaD
      through the influence of large-scale atmospheric circulation patterns, i.e. the
      Arctic Oscillation. These results will facilitate reconstruction of winter
      atmospheric circulation patterns over northwestern China based on a regional tree
      ring deltaD networks.

PMID- 25590540
TI  - A system-of-systems approach as a broad and integrated paradigm for sustainable
      engineered nanomaterials.
AB  - There is an urgent need for a trans-disciplinary approach for the collective
      evaluation of engineered nanomaterial (ENM) benefits and risks. Currently,
      research studies are mostly focused on examining effects at individual endpoints
      with emphasis on ENM risk effects. Less research work is pursuing the integration
      needed to advance the science of sustainable ENMs. Therefore, the primary
      objective of this article is to discuss the system-of-systems (SoS) approach as a
      broad and integrated paradigm to examine ENM benefits and risks to society,
      environment, and economy (SEE) within a sustainability context. The aims are
      focused on: (a) current approaches in the scientific literature and the need for
      a broad and integrated approach, (b) documentation of ENM SoS in terms of
      architecture and governing rules and practices within sustainability context, and
      (c) implementation plan for the road ahead. In essence, the SoS architecture is a
      communication vehicle offering the opportunity to track benefits and risks in an
      integrated fashion so as to understand the implications and make decisions about
      advancing the science of sustainable ENMs. In support of the SoS architecture, we
      propose using an analytic-based decision support system consisting of a knowledge
      base and analytic engine along the benefit and risk informatics routes in the SEE
      system to build sound decisions on what constitutes sustainable and unsustainable
      ENMs in spite of the existing uncertainties and knowledge gaps. The work
      presented herein is neither a systematic review nor a critical appraisal of the
      scientific literature. Rather, it is a position paper that largely expresses the
      views of the authors based on their expert opinion drawn from industrial and
      academic experience. 

PMID- 25590541
TI  - [In Process Citation].

PMID- 25590542
TI  - [Craving as a core symptom in substance use disorders: epidemiology,
      neurobiological substrates and clinical relevance].
AB  - OBJECTIVE: Observed by physicians and often reported by patients, craving is a
      core symptom of addiction, although not well defined nor understood completely.
      In the last several years, functional imaging as well as the measurement of
      different biological substrates of addiction have greatly evolved, allowing for a
      better understanding of the underlying neurobiological pathways of craving.
      Furthermore, with the development of the DSM-V and its inclusion as a diagnostic
      criterion for substance use disorders, craving has gained a whole new level of
      interest. Hence, the general objective of this article is to examine findings of
      studies that have led to a better understanding of craving and its implications.
      First, we address the definition of craving and its epidemiology in individuals
      with substance use disorders. We then summarize the results of the research
      conducted on the neurobiological substrates of craving. Finally, we present the
      role of craving in the cycle of addiction and its potential as a therapeutic
      target for pharmacological and non-pharmacological interventions. METHODS:
      Narrative review of the literature. RESULTS: The definition of craving has
      greatly evolved throughout the years, and it is commonly described as an abnormal
      desire or need to take a drug. While its conscious aspect is well known, whereas
      it is expressed subjectively, it is growingly also defined as an unconscious
      phenomenon illustrated by a physiologic activation that is not perfectly
      correlated with subjective measures. Available data on craving have also
      demonstrated the presence of this symptom in all three phases of the addiction
      cycle, including early and prolonged abstinence, long after the acute physical
      withdrawal syndrome. Three factors have been identified as potent craving
      inducers: the drug itself, drug related cues and stress. PET scan studies and
      fMRI studies confirmed the implication of dopaminergic pathways in craving, and
      have more recently shed light on the contribution of other neurotransmission
      systems, such as GABA, norepinephrine as well as the endocannabinoid and opioid
      systems, but their roles are not yet fully understood. Furthermore, craving
      related activations of specific areas of the brain involved in learned habits and
      behavior as well as memory have been demonstrated by various studies; in
      contrast, regions associated with regulation and control of emotion have been
      demonstrated to be hypoactive during craving episodes. Finally, several studies
      have demonstrated that craving is a valid predictive indicator of relapse, making
      it an interesting target for pharmacological and non-pharmacological treatment.
      Several anti-craving medications have been shown to decrease craving, including
      varenicline for tobacco and naltrexone for alcohol dependence. Studies examining
      the efficacy of other anti-craving medications for other substances are growing
      in numbers. CONCLUSIONS: Available data on craving support its role as a core
      symptom of addiction and allow for a better understanding of the underlying
      neurobiological substrates. Studies tend to show that it is a valid indicator of
      relapse during early and prolonged abstinence. Further research is needed to
      truly understand the complexity of the neurobiological substrates involved in
      craving as well as to develop new anti-craving interventions to facilitate long
      term abstinence in individuals with substance use disorders.

PMID- 25590543
TI  - [The Nature and Issues of Drug Addiction Treatment under Constraint].
AB  - OBJECTIVES: This article is exploring different forms of constraint that are
      exerted in the field of drug addiction treatment. The objective of this article
      is to establish benchmarks and to stimulate reflection about the ethical and
      clinical implications of those constraints in the field of drug addiction
      treatment. METHODS: This article is presenting a critical review of different
      forms of constraint that can be exerted in Canada in regard to the treatment of
      drug addiction. In the first section of the article, a definition of therapeutic
      intervention is proposed, that includes the dimension of power, which justifies
      the importance of considering the coercive aspects of treatment. The second
      section, which represents the core section of the paper, is devoted to the
      presentation of different levels of constraint that can be distinguished in
      regard to drug addicts who are under treatment. RESULTS: Three levels of
      constraint are exposed: judicial constraint, institutional constraint and
      relational constraint. The coercive aspect of treatment can then be recognized as
      a combination of all tree levels of constraint. Judicial constraint refers to any
      form of constraint in which the court or the judge is imposing or recommending
      treatment. This particular level of constraint can take different forms, such as
      therapeutic remands, conditions of a probation order, conditions of a conditional
      sentence of imprisonment, and coercive treatment such as the ones provided
      through drug courts. Institutional constraint refers to any form of constraint
      exerted within any institutional setting, such as correctional facilities and
      programs offered in community. Correctional facilities being limited by their own
      specific mission, it might have a major impact on the way the objectives of
      treatment are defined. Those limitations can then be considered as a form of
      constraint, in which drug users don't have much space to express their personal
      needs. Finally, relational constraint refers to any form of constraint in which
      the drug addict might be coerced to treatment under the pressure of people from
      the immediate environment, such as members of family, friends or employers. Even
      if this form of constraint is not as obvious as the ones exerted by court and
      correctional facilities, it has to be considered by practitioners who are
      evaluating the motivation of drug addicts under treatment. CONCLUSION:
      Considering the diversity of constraints that are exerted on drug addicts who are
      under treatment, it appears that we should be always aware of the ethical and
      clinical challenges facing practitioners every day. The recognition of those
      constraints can also help to understand how important it is to consider the
      institutional and social context in which treatment is being provided.

PMID- 25590544
TI  - [Are there any sex/gender differences in drug use and drug addiction?].
AB  - Drug use and drug addiction have been traditionally considered to be a male
      problem, however the gender gap has been decreasing over the past few decades.
      Thus, while the prevalence of alcohol, cannabis and nicotine dependence is still
      overall greater among men than among women, sex/gender differences in the abuse
      of stimulants and opiates seem to have disappeared. Moreover, women appear to be
      more prone to develop drug dependence, suffer more severe physical and
      psychological consequences of drug abuse, and have more difficulties quitting the
      habit. Numerous psychological, socio-cultural and biological factors have been
      implicated in these changing statistics. For example, while a large proportion of
      men initiate drug use to induce feelings of elation, energy or focus, women
      frequently start taking drugs to alleviate pre-existing mental health problems,
      including high levels of stress, feelings of alienation, depression, anxiety, or
      post-traumatic stress disorder. This maladaptive self-medication strategy often
      results in a faster transition to a habitual drug use and eventually a more
      severe dependence. In addition, the socio-cultural norms (particularly in the
      Western society) have changed dramatically over the past few decades. Thus, while
      there is still a more severe stigma and prejudice against women who use drugs
      (especially if they are pregnant of have children), overall there is much greater
      acceptance of women's drug use than it was several decades ago. Moreover, women
      have much greater access to various drugs of abuse than they used to have.
      Finally, over the past couple of decades new research started emerging pointing
      to some neurobiological factors that could also contribute to sex differences in
      drug addiction. Thus, there is now evidence that dopamine system, which for
      decades has been strongly implicated in drug reinforcement, is sexually
      dimorphic. The number of dopaminergic neurons, the density of the dopaminergic
      terminals, as well as responsiveness of the dopaminergic system to drugs of
      abuse, has been shown to differ between males and females and it has been shown
      to be modulated by sex steroid hormones, especially estrogen. For example, female
      rats exhibit greater motivation to self-administer cocaine than male rats and
      their motivation is the highest during elevated levels of estrogen. All these
      psychological, socio-cultural and biological factors that contribute to
      sex/gender difference in drug use and drug dependence, should be considered while
      evaluating and treating individuals with drug addiction problem. 

PMID- 25590545
TI  - [Psychosis and addiction: The evidence cemetery].
AB  - Objectives The comorbidity between psychosis and substance use has attracted wide
      attention over the years, and a vast literature is now available for meta
      analytic treatment. In the field, a majority of authors assume that cannabis
      smoking is a risk factor for psychosis, that substance abuse is highly prevalent
      in schizophrenia, that substance abuse worsens the prognosis of schizophrenia,
      and that integrated treatments have greater efficacy than treatment-as-usual for
      this complex population. The objective of the current article is to review the
      meta-analyses that have been published in the comorbidity field in order to
      determine if the above-mentioned assumptions are substantiated by evidence or
      not. Methods A search of the literature was performed using PubMed, PsycINFO and
      EMBASE. The literature search retrieved a total of 25 systematic quantitative
      reviews, addressing the following issues: etiology, age at onset, prevalence
      rates, cognition, treatment, as well as psychiatric, neurologic and functional
      outcomes. Results Evidence shows that the prevalence of tobacco smoking, cannabis
      smoking and alcohol use is elevated in psychosis. However, this prevalence is
      likely to be over-estimated since studies have been performed in clinical
      settings rather than the general population. Reliable evidence also suggests that
      cannabis smoking is a risk factor for psychosis outcomes. However, the
      association is rather small and it remains difficult to draw an unequivocal
      public health message from this literature. In the same vein, evidence suggests
      that cannabis smoking is associated with an earlier age at onset of psychosis.
      However, this observation is derived from cross-sectional studies, not
      longitudinal ones; thus, no undisputable claims on causality can be made from
      them. On clinical grounds, some evidence also suggests that substance use is
      associated with self-harm, increased positive and depressive symptoms in
      psychosis patients, but this evidence is derived from cross-sectional studies,
      not longitudinal ones. Cocaine may exacerbate antipsychotic-induced
      extrapyramidal symptoms in schizophrenia, but this observation is based on a
      small number of studies. In the case of violence, the aggregation of studies
      involving very large samples of patients has shown a strong association with
      substance abuse in psychosis patients. However, this association is based on
      statistics that are not adjusted for potential confounds, and the role of cluster
      B personality disorders in the substance abuse-violence association has yet to be
      determined from an evidence-based perspective. The effects of psychoactive
      substances on cognition in psychosis patients are inconsistent and contradictory.
      In terms of treatment, evidence shows that bupropion and varenicline increase
      tobacco smoking cessation rates in psychosis. However, this observation is based
      on a small number of studies. Finally, there is no evidence that integrated
      psychosocial interventions are superior to treatment as usual in this population.
      This lack of efficacy may due to a real lack of efficacy or to methodological
      problems making the comparison of intervention studies difficult. Discussion The
      evidence supporting the main assumptions of the comorbidity field is not as
      strong as it may seem. Moreover, important gaps in our understanding of the
      psychosis-addiction comorbidity remain. Due to lack of interest or lack of data,
      no meta-analysis has been performed, in the dual-diagnosis population, on
      injectable antipsychotics, subjective reasons for use, treatment compliance,
      medical comorbidities, the social context of use, the neurobiological links
      between substance use and psychosis, as well as the comparative efficacy of
      nicotine replacement therapy. 

PMID- 25590546
TI  - [Exploration of potential mechanisms underlying substance use disorders in
      individuals with personality disorders].
AB  - Background Cluster-B personality disorders (DSM-V), particularly borderline and
      antisocial personality disorders, are associated with high rates of substance use
      disorder. However, the mechanisms underlying this relationship have yet to be
      fully understood. Craving has recently been identified as an important component
      of substance use disorder. The purpose of this article is therefore to review the
      current literature and explore whether craving could be implicated as an
      underlying mechanism of comorbid substance use disorder in antisocial and
      borderline personality disorders.Method Critical review of the literature.Results
      Emerging evidence indicates that there is in fact an association between craving
      and personality disorders. Patients afflicted with the latter, incidentally,
      respond differently to anti-craving medication when compared to normal subjects.
      While a limited number of studies have directly assessed craving in patients with
      personality disorders, a growing number have looked at the association between
      craving and specific personality traits. The correlation between impulsivity,
      negative affect and craving seems like a plausible explanation for the high
      prevalence and severity of substance use disorder in subjects with antisocial or
      borderline personality disorders.Conclusion These findings suggest that specific
      personality traits are related to craving and could represent promising targets
      for the prevention, assessment and management of comorbid substance use
      disorders. 

PMID- 25590547
TI  - [Opioid use disorder in patients with chronic non-cancer pain].
AB  - Epidemiology Canada now has the second highest number of opioid prescriptions per
      capita in the world. The rate of prescriptions has increased over the last
      decade, most notably in adults over 55 years of age. A recognition of the
      importance of treating pain has influenced this increase, but higher rates of
      opioid prescribing have produced undesirable outcomes including the misuse of
      medication as well as an increased number of deaths and emergency department
      visits attributable to opioids. Diverse psychiatric disorders, such as major
      depression, now also occur in 40% of those with an opioid use disorder (OUD).
      Neuroscience We now understand that addictive behaviors are caused by both
      environmental and genetic factors. Although OUD has historically been perceived
      as a weakness of character, it is now clear that it is a chronic disease, which
      results from a complex interaction between a substance, such as opioid,
      environmental factors, and an individual's genotype. Unfortunately, this evidence
      has yet to be successfully translated into clinical practice and most physicians
      are unable to diagnose and manage OUD patients appropriately.Clinical guidelines
      Many clinical guidelines for the management of chronic, non-cancer pain are
      available. All guidelines identify the need to assess the patient appropriately
      and screen for factors associated with misuse before prescribing opioids.
      Guidelines generally acknowledge that patients should not be denied appropriate
      pain management, but that some patients will require close supervision and
      frequent follow-up to prevent the misuse of prescription opioids. 

PMID- 25590548
TI  - [Methamphetamine - just another stimulant or a more complex problem?].
AB  - Methamphetamine (MA) has recently become very popular in the media, due in part
      to its increasing popularity as well as its psychotropic effects and the negative
      consequences of its use. Is it a stimulant like any other, or does
      methamphetamine use lead to specific difficulties in its users? The aim of this
      article is to provide a brief review of the literature by explaining some of the
      reasons for its popularity in Canada as well as the physical, dental,
      psychiatric, cognitive and legal problems associated with its use. MA's
      popularity: Regarding its popularity, MA has benefitted from multiple factors,
      namely its low cost for users and manufacturers, its quick and intense
      psychotropic effects (increased energy, sexual arousal, rapid thinking,
      sleeplessness, lack of appetite), its easy access, as well as its various methods
      of ingestion (nasal, oral, injection). MA abuse also results in a multitude of
      negative effects, both physical and mental. MA's physical effects: In terms of
      negative physical effects, cardiac problems, skin infections, sexually
      transmitted (and injection-related) diseases as well as meth mouth are described.
      MA's mental effects: In terms of mental consequences, two recently published
      Canadian studies revealing high rates of depression symptoms and of sustained
      psychotic symptoms in a subgroup of MA users are presented. Studies reporting
      various cognitive deficits in MA user are also reviewed, including reports of
      high prevalence of childhood attention deficit and hyperactivity disorder
      diagnoses among adult MA users. Furthermore, MA abusers are documented as having
      been highly exposed to trauma in their lives, with many presenting with post
      traumatic stress disorder criteria. This manuscript also explores the reasons
      behind the forensic profiles of individuals using MA, particularly the increased
      tendency toward violent acts, the high incarceration rates of the homeless users
      and the high percentage of individuals diagnosed with antisocial personality
      disorder reported in studies. In terms of user profiles, various methods of
      ingestion, frequency of use as well as combination with other drugs are
      described, with a special focus on the frequent polysubstance abuse found in MA
      users and the reality of bingers. TREATMENT: This manuscript describes specific
      treatments designed for stimulant users such as MA abusers, namely the MATRIX
      program, as well as modifications piloted for those with comorbid depression.
      Pharmacological treatments, as well as antioxidant supplements, are also
      discussed although they have not yielded positive results with humans to date.
      Overall, our goal in this manuscript is to highlight the complexity of the
      difficulties faced by MA users as well as the limited ability of currently
      available treatments to address the multiple needs associated with this
      complexity.

PMID- 25590549
TI  - [Internet addiction: a descriptive clinical study of people asking for help in
      rehabilitation treatment center in Quebec: exploratory study].
AB  - To date, there is no consensus on the diagnostic criteria for Internet addiction
      (Hinic, 2011; Tonioni & coll., 2012; Weinstein & Lejoyeux, 2010). Nonetheless,
      some people consider themselves cyberdependent and request treatment services in
      the addiction rehabilitation centers (ARC) of the province of Quebec. These
      admissions have led the Health and Social Services Agency of Montreal to ask for
      the realization of a descriptive study on Internet addiction. OBJECTIVES: 1)
      Describe the socio-demographical characteristics of cyberdependent individuals
      receiving treatment in the ARC; 2) Document their associated problems, such as
      problems related to alcohol and drug abuse, gambling, self-esteem, and symptoms
      of depression and anxiety. METHODOLOGY: The study was conducted in eight ARC's of
      the province of Quebec. A convenience sample of 57 people was recruited over a
      period of 24 months, from 2010 to 2012. To participate in this study, individuals
      had to be 18 years or older, identify themselves as cyberdependent, and request
      help for an Internet addiction problem in a public ARC. The Internet Addiction
      Test (Young, 1998), in its validated French version (Khazaal & coll., 2008), was
      used to assess the severity of Internet use habits. The associated problems were
      assessed using the following questionnaires: the Beck Anxiety Inventory (Beck,
      Epstein, Brown & Steer, 1988); the Beck Depression Inventory, in its validated
      French version (Bourque & Beaudette, 1982); the DEBA-Alcool/Drogues/Jeu
      (Depistage-evaluation du besoin d'aide), an instrument used to screen and assess
      the need for help in problems related to alcohol, drugs, and gambling (Tremblay &
      Blanchette-Martin, 2009), and the Rosenberg's Self-Esteem Scale (Rosenberg,
      1965). RESULTS: Fifty-seven people agreed to participate in the study. A large
      majority of these cyberdependent individuals were male (88%), the mean age was 30
      years old, had low incomes and were living with their parents. They consulted
      following the pressure of their entourage and reported many consequences due to
      their Internet addiction problem.They spent, on average, 65.8 hours per week on
      the Internet and reported having several problematic applications. Amongst these
      problematic applications, the most frequently reported were the role playing game
      (MMORPG) (57.8%), the streaming on entertainment sites (35.1%), and the chat
      rooms (29.8%). Regarding the self-esteem scale, 66.6% of participants presented a
      very low or low self-esteem, while 21.1% presented an above average self-esteem.
      According to Beck Depression and Anxiety Inventories, 3.5% (n=2) of the sample
      reached the clinical threshold for depression, while 7.5% (n=4) reached it for
      anxiety. Almost half (45.6%) of the participants were taking psychotropic
      medication for a mental health problem, and 33.3% had a chronic physical health
      problem. CONCLUSION: This study highlights the characteristics of a still unknown
      group in the population, that of cyberdependent people. Individuals having an
      Internet addiction problem live significant consequences due to the loss of
      control on their Internet use. In addition, when they are admitted into
      treatment, even if the subjective psychological distress is not always high,
      participants present a complex clinical profile, where comorbidity is the rule
      rather than the exception. We believe that the current data show enough
      similarities with other addictive disorders, to allow clinicians to work taking
      into consideration their experience with other addictive behaviours.

PMID- 25590550
TI  - [Noise Effects on Mental Health: a review of literature].
AB  - Any human activity generates noise. It is considered as a risk factor for
      people's health. The present review of literature has assessed the impact of
      noise on mental health; it is summarized into four points: objective, methods,
      results and conclusion. OBJECTIVE: The main objective of this study is to expose
      the actual knowledge state of noise effects on mental health after overview and
      critical analysis of literature to identify the acquired and shortcomings, to
      reflect on research direction in terms of noise pollution in the future. METHODS:
      The literature review was conducted based on: research of keys words in articles
      published, research of the number of quotations of articles in Journal Citation
      Reports (JCR), published in web of science, research of impact factor of
      journals. One hundred articles were selected, after analyzing contents, items
      were classified into: fundamental studies (25%), experimental studies (50%), and
      epidemiological studies (25%). RESULTS: The fundamental studies have verified the
      hypothesis according to which noise generates stress. Researchers have dosed
      hormones of stress in plasma, urine and saliva in individuals exposed to noise of
      different decibels. The results found were unanimous: The rates of stress
      hormones found, were significantly high in three liquids. This means that noise
      causes stress. For experimental studies, researchers have experienced the role of
      noise on memory, attention and performance. Human subjects were exposed to
      different decibels to assess level of disruption to their memory, attention, and
      performance. The results revealed that noise disturbs memory, distracts attention
      and decreases performance. Experimental studies are the most abundant and
      constitute 50% of the current literature review.The epidemiological studies have
      evaluated the intellectual performance of students in schools located in noisy
      environments and residents in areas surrounding airports, railways and highways.
      RESULTS have revealed that students in schools located in noisy environments have
      presented cognitive impairment. CONCLUSION: This review of literature on noise
      effects on mental health lead to the following conclusion. It seems to exist a
      consensus in fundamental and experimental studies on the detrimental effect of
      noise but results from epidemiological are not convincing and require further
      studies.

PMID- 25590551
TI  - [Neurocognitive insight in schizophrenia: a meta-analysis].
AB  - Background Schizophrenia is well-known to be associated with a lack of insight
      into symptoms. Comparatively, little is known on insight into neurocognitive
      deficits in schizophrenia, despite the fact that these dysfunctions are
      undoubtedly core features of the disorder. Recently, growing interest has been
      paid to subjective cognition, and thus far, results have been heterogeneous. The
      objectives of current meta-analysis were to determine the magnitude of subjective
      complaints in schizophrenia; to examine the association between subjective
      cognitive complaints and objective cognition, as well psychiatric symptoms and
      insight into illness. The meta-analysis also sought to determine if results are
      influenced by the choice of the scale used to measure subjective cognition.
      Methods A search was performed with PubMed, PsycInfo and EMBASE, using the
      following key words: schizophrenia OR psychosis AND cognition OR memory OR
      attention OR "executive functions" AND insight OR "subjective cognition" OR
      awareness. Studies involving patients with schizophrenia-spectrum disorders and
      measuring subjective cognition with a validated self-report scale were included.
      Studies using scales measuring insight into thinking processes (e.g. Beck
      Cognitive Insight Scale) were excluded. Statistical analyses were performed with
      the Comprehensive Meta-Analysis-2 software. Cognitive scores were grouped into 6
      cognitive domains (as recommended by the MATRICS group): attention, problems
      solving, speed of processing, verbal memory, visual memory and working memory.
      The difference in cognitive complaints between schizophrenia patients and healthy
      controls was examined using Cohen's d. The associations between subjective
      cognition and objective cognition, psychiatric symptoms and insight into illness
      were examined using Pearson's correlation coefficients. Results Twenty-two
      studies were retrieved, including a total of 1609 patients and 294 controls.
      Patients reported increased subjective cognitive complaints, compared to controls
      (moderate effect size). A weak association was observed between subjective and
      objective (global) cognition. The association was larger in studies using the
      Subjective Scale To Investigate Cognition in Schizophrenia (SSTICS), compared to
      studies using other scales. The largest association was observed between
      subjective complaints and problem solving. The association between subjective
      complaints and depressive symptoms was in the same range as the association
      between subjective complaints (measured with the SSTICS) and objective cognition.
      No association was found between subjective complaints and positive / negative
      symptoms. Finally, a weak association was found between subjective complaints and
      insight into illness. Discussion Taken together, these results suggest that
      schizophrenia patients report significant subjective cognitive complaints.
      However, patients have a poor understanding of these deficits, since subjective
      complaints are as strongly associated with depressive symptoms as they are
      associated with objective cognitive deficits. Schizophrenia patients may be more
      aware of their problem solving deficits. However, this observation is based on a
      limited number of studies and will need to be replicated in future studies. Our
      results also show that insight into neurocognitive deficits is largely
      independent from insight into illness. Finally, the results of the current meta
      analysis may have methodological implications, since they suggest that the SSTICS
      produces stronger associations between subjective and objective cognition than
      other scales. In the future, greater attention will need to be paid to the
      domains of subjective complaints, as well as to subjective cognitive complaints
      in other psychiatric disorders. 

PMID- 25590552
TI  - [Early intervention in psychosis: concepts, current knowledge and future
      directions].
AB  - OBJECTIVES: This paper seeks to provide an overview of the motives, rationale,
      theoretical underpinnings and foundational literature of the early intervention
      movement for psychoses. It also seeks to review the current status of the field,
      highlight its significant developments and identify its emergent trends. METHODS:
      This paper begins by contextualizing the burden of psychosis. It then traces the
      origins of the early intervention movement and surveys the seminal literature
      that established and shapes the field. It describes the movement's characteristic
      elements, types, approaches, strengths, criticisms and trajectories in select
      Western nations. It closes with a presentation of how the early intervention
      movement is informing broader endeavours to transform youth mental health.
      RESULTS: We find that the early intervention movement is predicated on the
      critical period hypothesis that emphasizes the significance of the early stages
      of the illness; and on findings that the duration of untreated psychosis
      influences prognoses. Early intervention redresses this situation by facilitating
      access to specialized, phase-specific treatment. Access is enhanced through open
      referral, fast response times, and public and practitioner education. Ideally,
      the intervention, provided for the first two years after detection, features
      intensive case management; low-dose antipsychotic medication; an emphasis on
      social functioning; family intervention; early attention to comorbid concerns;
      and due regard for the needs and priorities of youth and their families. Evidence
      suggests that specialized early intervention yields better outcomes than routine
      care. The cost-effectiveness of such services has not yet been definitely
      investigated. Criticisms of early intervention pertain to the quality of evidence
      for, the manner of implementation of, the allocation of resources to early
      intervention and its utility for persons at high risk for developing psychosis.
      We also identify advocacy within the field for extending early intervention to
      the first five years of the course of psychosis. CONCLUSION: We conclude that the
      status of the early intervention movement (in terms of availability and policy)
      in Western public healthcare systems can be resolved into a spectrum. The United
      Kingdom is shown to be the leader while Canada appears at the middle of the
      spectrum (with the United States bringing up the rear). In the Quebec context,
      the picture is found to be mixed and recommendations for further research and
      investment are made. Finally, an examination is undertaken of how the early
      intervention for psychosis movement has provided the impetus for and dovetails
      into the larger effort to transform youth mental healthcare in general, a
      development that is in its nascent stages in Canada.

PMID- 25590553
TI  - [Transference in the treatment of dissociative identity disorder: A review of
      literature and a case example].
AB  - A literature review about transference in the treatment of dissociative identity
      disorder (DID) is presented. Common transference reactions resulting from serious
      traumas are explored, considering that those kind of trauma are higly present in
      the pathways of DID patients. Post traumatic transference aspects specific to DID
      are also presented. In addition, common transference patterns and dissociative
      aspects of transference in the treatment of DID are explained. Transference is
      also discussed in relationship to the possible impact of disorganized attachment,
      which is a main component in the development of DID. The clinical implications of
      this proposition will be discussed and supported by a case example. 

PMID- 25590554
TI  - [First stage in identifying traumatic profil inpatients hospitalised in
      psychiatry in Martinique].
AB  - The population hospitalised in psychiatry seems more exposed to traumatic events
      than the French general population, with particularly more sexual aggressions.
      The aim of this study is to describe the population hospitalised in psychiatry
      and more precisely the traumatic history of these patients, their comorbidities
      (mental diseases and addictions), and socio economical level. This descriptive,
      cross sectional and retrospective study took place in the Crisis Center in the
      University Hospital in Martinique (French West Indies), from February to July
      2013. A socio-demographic information, the Mini International Neuropsychiatric
      Interview 5.0, the Trauma History Questionnaire and the Impact Events Scale
      Revised were realised with 49 of the 143 patients admitted during this period
      (34.3%). In this population, we found a mean of 6.5 (standart-deviation=4.2)
      different types of traumatic event, with 38.8% patients reporting a natural
      disaster, and 38.8% declaring at least one sexual aggression. In the 25 patients
      suffering from post-traumatic stress disorder, 66.7% underwent a sexual
      aggression, significatively during childhood (before 10 years old, P=0.01), and
      during adolescence (between 10 to 18 years old, P=0.01). These results underline
      the importance of a systematic screening of the traumatic profile: the
      characteristics of the traumatic events and its clinical impact. 

PMID- 25590555
TI  - Uniformly embedded silver nanomesh as highly bendable transparent conducting
      electrode.
AB  - Ag-nanomesh-based highly bendable conducting electrodes are developed using a
      combination of metal nanotransfer printing and embossing for the 6-inch wafer
      scale. Two Ag nanomeshes, including pitch sizes of 7.5 and 10 MUm, are used to
      obtain highly transparent (approximately 85% transmittance at a wavelength of 550
      nm) and electrically conducting properties (below 10 Omega sq(-1)). The Ag
      nanomeshes are also distinguished according to the fabrication process, which is
      called transferred or embedded Ag nanomesh on polyethylene terephthalate (PET)
      substrate, in order to compare their stability against bending stress. Then the
      enhancement of bending stability when the Ag nanomesh is embedded in the PET
      substrate is confirmed. 

PMID- 25590557
TI  - Analyzing the effects of stromal cells on the recruitment of leukocytes from
      flow.
AB  - Stromal cells regulate the recruitment of circulating leukocytes during
      inflammation through cross-talk with neighboring endothelial cells. Here we
      describe two in vitro "vascular" models for studying the recruitment of
      circulating neutrophils from flow by inflamed endothelial cells. A major
      advantage of these models is the ability to analyze each step in the leukocyte
      adhesion cascade in order, as would occur in vivo. We also describe how both
      models can be adapted to study the role of stromal cells, in this case
      mesenchymal stem cells (MSC), in regulating leukocyte recruitment. Primary
      endothelial cells were cultured alone or together with human MSC in direct
      contact on Ibidi microslides or on opposite sides of a Transwell filter for 24
      hr. Cultures were stimulated with tumor necrosis factor alpha (TNFalpha) for 4 hr
      and incorporated into a flow-based adhesion assay. A bolus of neutrophils was
      perfused over the endothelium for 4 min. The capture of flowing neutrophils and
      their interactions with the endothelium was visualized by phase-contrast
      microscopy. In both models, cytokine-stimulation increased endothelial
      recruitment of flowing neutrophils in a dose-dependent manner. Analysis of the
      behavior of recruited neutrophils showed a dose-dependent decrease in rolling and
      a dose-dependent increase in transmigration through the endothelium. In co
      culture, MSC suppressed neutrophil adhesion to TNFalpha-stimulated endothelium.
      Our flow based-adhesion models mimic the initial phases of leukocyte recruitment
      from the circulation. In addition to leukocytes, they can be used to examine the
      recruitment of other cell types, such as therapeutically administered MSC or
      circulating tumor cells. Our multi-layered co-culture models have shown that MSC
      communicate with endothelium to modify their response to pro-inflammatory
      cytokines, altering the recruitment of neutrophils. Further research using such
      models is required to fully understand how stromal cells from different tissues
      and conditions (inflammatory disorders or cancer) influence the recruitment of
      leukocytes during inflammation. 

PMID- 25590558
TI  - Meiotic crossover patterns: obligatory crossover, interference and homeostasis in
      a single process.
AB  - During meiosis, crossover recombination is tightly regulated. A spatial
      patterning phenomenon known as interference ensures that crossovers are well
      spaced along the chromosomes. Additionally, every pair of homologs acquires at
      least one crossover. A third feature, crossover homeostasis, buffers the system
      such that the number of crossovers remains steady despite decreases or increases
      in the number of earlier recombinational interactions. Here we summarize recent
      work from our laboratory supporting the idea that all 3 of these aspects are
      intrinsic consequences of a single basic process and suggesting that the
      underlying logic of this process corresponds to that embodied in a particular
      (beam-film) model. 

PMID- 25590560
TI  - Elucidating the fundamental mechanisms of cell death triggered by photothermal
      therapy.
AB  - Photothermal therapy (PTT) utilizes nanoparticles embedded within tumors as
      exogenous energy absorbers to convert laser light energy into heat to ablate
      cancer cells. While PTT is a promising alternative to conventional cancer
      therapy, under certain irradiation conditions, it can produce cellular necrosis,
      and this necrosis may lead to pro-inflammatory responses that are detrimental to
      treatment success. Recent studies have shown that PTT can be modulated to induce
      apoptosis rather than necrosis, which is appealing since apoptosis discourages an
      inflammatory response. In this issue of ACS Nano, del Pino, Pardo, de la Fuente,
      and colleagues reveal the intracellular signaling cascades involved in the
      apoptotic response to PTT using cells harboring photothermal transducing
      nanoprisms. In this Perspective, we present an overview of nanoparticle-mediated
      PTT and discuss photothermally induced apoptosis as a potential therapeutic
      pathway. 

PMID- 25590559
TI  - Functional relationship among PLK2, PLK4 and ROCK2 to induce centrosome
      amplification.
AB  - The presence of more than 2 centrosomes (centrosome amplification) leads to
      defective mitosis and chromosome segregation errors, is frequently found in a
      variety of cancer types, and believed to be the major cause of chromosome
      instability. One mechanism for generation of amplified centrosomes is over
      duplication of centrosomes in a single cell cycle, which is expected to occur
      when cells are temporarily arrested. There are a growing number of kinases that
      are critical for induction and promotion of centrosome amplification in the cell
      cycle-arrested cells, including Rho-associated kinase (ROCK2), Polo-like kinase 2
      (PLK2) and PLK4. Here, we tested whether these kinases induce centrosome
      amplification in a linear pathway or parallel pathways. We first confirmed that
      ROCK2, PLK2 and PLK4 are all essential for centrosomes to re-duplicate in the
      cells arrested by exposure to DNA synthesis inhibitor. Using the centrosome
      amplification rescue assay, we found that PLK2 indirectly activates ROCK2 via
      phosphorylating nucleophosmin (NPM), and PLK4 functions downstream of ROCK2 to
      drive centrosome amplification in the arrested cells. 

PMID- 25590561
TI  - Assessment of viability of human fat injection into nude mice with micro-computed
      tomography.
AB  - Lipotransfer is a vital tool in the surgeon's armamentarium for the treatment of
      soft tissue deficits of throughout the body. Fat is the ideal soft tissue filler
      as it is readily available, easily obtained, inexpensive, and inherently
      biocompatible.(1) However, despite its burgeoning popularity, fat grafting is
      hampered by unpredictable results and variable graft survival, with published
      retention rates ranging anywhere from 10-80%. (1-3) To facilitate investigations
      on fat grafting, we have therefore developed an animal model that allows for real
      time analysis of injected fat volume retention. Briefly, a small cut is made in
      the scalp of a CD-1 nude mouse and 200-400 ul of processed lipoaspirate is placed
      over the skull. The scalp is chosen as the recipient site because of its absence
      of native subcutaneous fat, and because of the excellent background contrast
      provided by the calvarium, which aids in the analysis process. Micro-computed
      tomography (micro-CT) is used to scan the graft at baseline and every two weeks
      thereafter. The CT images are reconstructed, and an imaging software is used to
      quantify graft volumes. Traditionally, techniques to assess fat graft volume have
      necessitated euthanizing the study animal to provide just a single assessment of
      graft weight and volume by physical measurement ex vivo. Biochemical and
      histological comparisons have likewise required the study animal to be
      euthanized. This described imaging technique offers the advantage of visualizing
      and objectively quantifying volume at multiple time points after initial grafting
      without having to sacrifice the study animal. The technique is limited by the
      size of the graft able to be injected as larger grafts risk skin and fat
      necrosis. This method has utility for all studies evaluating fat graft viability
      and volume retention. It is particularly well-suited to providing a visual
      representation of fat grafts and following changes in volume over time. 

PMID- 25590562
TI  - The clinical value of whole blood point-of-care biomarkers in large animal
      emergency and critical care medicine.
AB  - OBJECTIVE: To summarize the current medical literature and provide a clinical
      perspective of whole blood point-of-care (POC) biomarkers in large animal
      emergency and critical care practice. DATA SOURCES: Original studies, reviews,
      and textbook chapters in the human and veterinary medical fields. SUMMARY: POC
      biomarkers are tests used to monitor normal or disease processes at or near the
      patient. In both human and veterinary medicine these tools are playing an
      increasingly important role in the management of critical diseases. The most
      important whole blood POC biomarkers available for veterinary practitioners
      include l-lactate, cardiac troponin I, serum amyloid A, triglyceride, creatinine,
      and glucose, although many other tests are available or on the horizon.
      CONCLUSION: Whole blood POC biomarkers enable clinicians to provide improved
      management of critical diseases in large animals. These tools are especially
      useful for establishing a diagnosis, guiding therapy, and estimating disease risk
      and prognosis.

PMID- 25590563
TI  - Neural network for constrained nonsmooth optimization using Tikhonov
      regularization.
AB  - This paper presents a one-layer neural network to solve nonsmooth convex
      optimization problems based on the Tikhonov regularization method. Firstly, it is
      shown that the optimal solution of the original problem can be approximated by
      the optimal solution of a strongly convex optimization problems. Then, it is
      proved that for any initial point, the state of the proposed neural network
      enters the equality feasible region in finite time, and is globally convergent to
      the unique optimal solution of the related strongly convex optimization problems.
      Compared with the existing neural networks, the proposed neural network has lower
      model complexity and does not need penalty parameters. In the end, some numerical
      examples and application are given to illustrate the effectiveness and
      improvement of the proposed neural network. 

PMID- 25590565
TI  - Black titanium dioxide (TiO2) nanomaterials.
AB  - In the past few decades, there has been a wide research interest in titanium
      dioxide (TiO2) nanomaterials due to their applications in photocatalytic hydrogen
      generation and environmental pollution removal. Improving the optical absorption
      properties of TiO2 nanomaterials has been successfully demonstrated to enhance
      their photocatalytic activities, especially in the report of black TiO2
      nanoparticles. The recent progress in the investigation of black TiO2
      nanomaterials has been reviewed here, and special emphasis has been given on
      their fabrication methods along with their various chemical/physical properties
      and applications. 

PMID- 25590564
TI  - Chemotherapy-induced vascular toxicity--real-time in vivo imaging of vessel
      impairment.
AB  - Certain classes of chemotherapies may exert acute vascular changes that may
      progress into long-term conditions that may predispose the patient to an
      increased risk of vascular morbidity. Yet, albeit the mounting clinical evidence,
      there is a paucity of clear studies of vascular toxicity and therefore the
      etiology of a heterogeneous group of vascular/cardiovascular disorders remains to
      be elucidated. Moreover, the mechanism that may underlie vascular toxicity can
      completely differ from the principles of chemotherapy-induced cardiotoxicity,
      which is related to direct myocyte injury. We have established a real-time, in
      vivo molecular imaging platform to evaluate the potential acute vascular toxicity
      of anti-cancer therapies. We have set up a platform of in vivo, high-resolution
      molecular imaging in mice, suitable for visualizing vasculature within confined
      organs and reference blood vessels within the same individuals whereas each
      individual serve as its own control. Blood vessel walls were impaired after
      doxorubicin administration, representing a unique mechanism of vascular toxicity
      that may be the early event in end-organ injury. Herein, the method of fibered
      confocal fluorescent microscopy (FCFM) based imaging is described, which provides
      an innovative mode to understand physiological phenomena at the cellular and sub
      cellular levels in animal subjects. 

PMID- 25590566
TI  - Effect of focused ion beam deposition induced contamination on the transport
      properties of nano devices.
AB  - Focused ion beam (FIB) deposition produces unwanted particle contamination beyond
      the deposition point. This is due to the FIB having a Gaussian distribution. This
      work investigates the spatial extent of this contamination and its influence on
      the electrical properties of nano-electronic devices. A correlation study is
      performed on carbon-nanotube (CNT) devices manufactured using FIB deposition. The
      devices are observed using transmission electron microscopy (TEM) and these
      images are correlated with device electrical characteristics. To discover how far
      Pt-nanoparticle contamination occurs along a CNT after FIB electrical contact
      deposition careful TEM inspections are performed. The results show FIB deposition
      efficiently improves electrical contact; however, the practice is accompanied by
      serious particle contamination near deposition points. These contaminants include
      metal particles and amorphous elements originating from precursor gases and
      residual water molecules in the vacuum chamber. Pt-contamination extends for
      approximately 2 MUm from the point of FIB contact deposition. These contaminants
      cause current fluctuations and alter the transport characteristics of devices. It
      is recommended that nano-device fabrication occurs at a distance greater than 2
      MUm from the FIB deposition of an electrical contact. 

PMID- 25590567
TI  - Dry grinding effect on pyrophyllite-quartz natural mixture and its influence on
      the structural alternation of pyrophyllite.
AB  - Infrared spectroscopy (IR), scanning electron microscopy (SEM), X-ray diffraction
      (XRD), and high-resolution transmission electron microscopy (HRTEM) with energy
      dispersive X-ray analysis (EDS) were used to investigate the evolution of
      mechanical destruction of the pyrophyllite structure and final ground products
      upon grinding with a laboratory planetary ball mill. The raw ore used in this
      present work was mainly composed of pyrophyllite and quartz. This pyrophyllite
      was more resistant toward mechanical destruction, and the crystalline order of
      pyrophyllite was not completely destroyed until grinding for 240 min with a 20:1
      of weight ratio of the balls to powder. The existing crystalline phase in the
      final ground product was found to be quartz, which served as the associated phase
      in the original pyrophyllite mineral. The rate of destruction of pyrophyllite
      structure depended on the types of chemical bonds. Additionally, increasing the
      intensity of grinding resulted in acceleration of the mechanically induced
      amorphization of the pyrophyllite structure, whereas the associated quartz grains
      contributed to the deceleration of the amorphization of pyrophyllite.

PMID- 25590568
TI  - Silicone oil emulsification at the fovea as a reversible cause of vision loss.

PMID- 25590569
TI  - Whole mount labeling of cilia in the main olfactory system of mice.
AB  - The mouse olfactory system comprises 6-10 million olfactory sensory neurons in
      the epithelium lining the nasal cavity. Olfactory neurons extend a single
      dendrite to the surface of the epithelium, ending in a structure called dendritic
      knob. Cilia emanate from this knob into the mucus covering the epithelial
      surface. The proteins of the olfactory signal transduction cascade are mainly
      localized in the ciliary membrane, being in direct contact with volatile
      substances in the environment. For a detailed understanding of olfactory signal
      transduction, one important aspect is the exact morphological analysis of
      signaling protein distribution. Using light microscopical approaches in
      conventional cryosections, protein localization in olfactory cilia is difficult
      to determine due to the density of ciliary structures. To overcome this problem,
      we optimized an approach for whole mount labeling of cilia, leading to improved
      visualization of their morphology and the distribution of signaling proteins. We
      demonstrate the power of this approach by comparing whole mount and conventional
      cryosection labeling of Kirrel2. This axon-guidance adhesion molecule is known to
      localize in a subset of sensory neurons and their axons in an activity-dependent
      manner. Whole mount cilia labeling revealed an additional and novel picture of
      the localization of this protein. 

PMID- 25590571
TI  - Message from the Editor-in-Chief.
AB  - One year after I assumed the position of Editor in Chief of Life, it is my great
      pleasure to write this editorial highlighting our achievements during this
      period, which were so many! As I wrote in the first editorial, my commitment was
      to make the journal a success, with the launch of exciting special issues,
      publication of high quality papers as well as inclusion of the journal in major
      indexing and abstracting services [1]. Basically, throughout 2014, all these
      commitments have been accomplished. Several eminent team leaders have joined our
      editorial board [2], timely special issues have been launched [3], and the
      journal already was indexed in PubMed [4]; now, it is just a matter of time to be
      indexed in Web of Science. The feedback from the scientific community already has
      been quite positive. With timely special issues lined up for 2015, the journal is
      developing quite fast.[...]. 

PMID- 25590572
TI  - Octahedral metal clusters as building blocks of trimetallic superexpanded
      Prussian blue analogues.
AB  - The self-assembly of octahedral metal clusters (diamagnetic
      [Nb(6)Cl(12)(CN)(6)](4-) or paramagnetic [Ta(6)Cl(12)(CN)(6)](3-)),
      [Mn(salen)](+) [salen = N,N'-ethylenebis(salicylidene)iminate] and mononuclear
      {M'(CN)(x)} polycyanometallates ([Fe(CN)(6)](4-), [Cr(CN)(6)](3-),
      [Fe(CN)(5)(NO)](2-), or [Ni(CN)(4)](2-)) building blocks results in the formation
      of a series of six cluster-containing 3D heterotrimetallic frameworks:
      [H(3)O](2)[Nb(6)Cl(12)(CN)(6)[Mn(salen)](6)Fe(CN)(6)].3H(2)O (1),
      [H(3)O][Nb(6)Cl(12)(CN)(6)[Mn(salen)](6)Cr(CN)(6)].4H(2)O (2),
      [Nb(6)Cl(12)(CN)(6)[Mn(salen)](6)Fe(CN)(5)(NO)].5H(2)O (3),
      [Nb(6)Cl(12)(CN)6[Mn(salen)](6)Ni(CN)4].7H(2)O (4),
      [H(3)O][Ta(6)Cl(12)(CN)(6)[Mn(salen)](6)Fe(CN)6].4H(2)O (5), and
      [Ta(6)Cl(12)(CN)(6)[Mn(salen)](6)Cr(CN)(6)].7H(2)O (6). Single-crystal X-ray
      diffraction analyses show that compounds 1, 2, 5, and 6 have distorted face
      centered-cubic frameworks that can be considered as superexpanded Prussian blue
      analogues built of two different hexacyanometallate nodes and expanded by
      insertion of the [Mn(salen)](+) complex, while 4 features a quasi-superexpanded
      Prussian blue framework because the structure is based on the hexacyano metal
      cluster and disordered tetracyano [Ni(CN)(4)](2-) nodes. The powder X-ray
      diffraction of 3 indicates that it possesses a quasi-superexpanded Prussian blue
      framework based on the hexacyano cluster and disordered pentacyano
      [Fe(CN)(5)(NO)](2-) nodes. Compound 6 is the first compound containing three 3d
      3d'-M6 cluster (4d) spin centers. Magnetic measurements reveal that the overall
      magnetic nature can be systematically controlled by the choice of the octahedral
      metal cluster and polycyanometallate nodes. H(2)/N(2) adsorption and thermal
      stability of the compounds were investigated.

PMID- 25590570
TI  - Emergent chemical behavior in variable-volume protocells.
AB  - Artificial protocellular compartments and lipid vesicles have been used as model
      systems to understand the origins and requirements for early cells, as well as to
      design encapsulated reactors for biotechnology. One prominent feature of vesicles
      is the semi-permeable nature of their membranes, able to support passive
      diffusion of individual solute species into/out of the compartment, in addition
      to an osmotic water flow in the opposite direction to the net solute
      concentration gradient. Crucially, this water flow affects the internal aqueous
      volume of the vesicle in response to osmotic imbalances, in particular those
      created by ongoing reactions within the system. In this theoretical study, we pay
      attention to this often overlooked aspect and show, via the use of a simple semi
      spatial vesicle reactor model, that a changing solvent volume introduces
      interesting non-linearities into an encapsulated chemistry. Focusing on
      bistability, we demonstrate how a changing volume compartment can degenerate
      existing bistable reactions, but also promote emergent bistability from very
      simple reactions, which are not bistable in bulk conditions. One particularly
      remarkable effect is that two or more chemically-independent reactions, with
      mutually exclusive reaction kinetics, are able to couple their dynamics through
      the variation of solvent volume inside the vesicle. Our results suggest that
      other chemical innovations should be expected when more realistic and active
      properties of protocellular compartments are taken into account. 

PMID- 25590573
TI  - Comparative study of vapor- and solution-crystallized perovskite for planar
      heterojunction solar cells.
AB  - Organometal halide perovskite (CH3NH3PbI3) could be crystallized by exposing PbI2
      to either CH3NH3I solution or CH3NH3I vapor. Though high performance was achieved
      in both approaches, it was still not clear which approach would be more desirable
      for device performance in principle. Herein, we addressed this issue by
      investigating the influence of crystallization condition on perovskite
      morphology, and subsequently on device performances. We found that vapor
      crystallized perovskite devices demonstrated smoother surface morphology, better
      light absorption, lower charge recombination, and thus much higher conversion
      efficiency than solution-crystallized devices, which would give some useful
      enlightenment to develop high-performance planar perovskite solar cells. 

PMID- 25590575
TI  - Noncovalent magnetic control and reversible recovery of graphene oxide using iron
      oxide and magnetic surfactants.
AB  - The unique charging properties of graphene oxide (GO) are exploited in the
      preparation of a range of noncovalent magnetic GO materials, using
      microparticles, nanoparticles, and magnetic surfactants. Adsorption and
      desorption are controlled by modification of pH within a narrow window of <2 pH
      units. The benefit conferred by using charge-based adsorption is that the process
      is reversible, and the GO can be captured and separated from the magnetic
      nanomaterial, such that both components can be recycled. Iron oxide (Fe2O3)
      microparticles form a loosely flocculated gel network with GO, which is
      demonstrated to undergo magnetic compressional dewatering in the presence of an
      external magnetic field. For composites formed from GO and Fe2O3 nanoparticles,
      it is found that low Fe2O3:GO mass ratios (<5:1) favor flocculation of GO,
      whereas higher ratios (>5:1) cause overcharging of the surfaces resulting in
      restabilization. The effectiveness of the GO adsorption and magnetic capture
      process is demonstrated by separating traditionally difficult-to-recover gold
      nanoparticles (d ~ 10 nm) from water. The fully recyclable nature of the assembly
      and capture process, combined with the vast adsorption capacity of GO, presents
      obvious and appealing advantages for applications in decontamination and water
      treatment. 

PMID- 25590574
TI  - Learning faces: similar comparator faces do not improve performance.
AB  - Recent evidence indicates that comparison of two similar faces can aid subsequent
      discrimination between them. However, the fact that discrimination between two
      faces is facilitated by comparing them directly does not demonstrate that
      comparison produces a general improvement in the processing of faces. It remains
      an open question whether the opportunity to compare a "target" face to similar
      faces can facilitate the discrimination of the exposed target face from other
      nonexposed faces. In Experiment 1, selection of a target face from an array of
      novel foils was not facilitated by intermixed exposure to the target and
      comparators of the same sex. Experiment 2 also found no advantage for similar
      comparators (morphed towards the target) over unmorphed same sex comparators, or
      over repeated target exposure alone. But all repeated exposure conditions
      produced better performance than a single brief presentation of the target.
      Experiment 3 again demonstrated that repeated exposure produced equivalent
      learning in same sex and different sex comparator conditions, and also showed
      that increasing the number of same sex or different sex comparators failed to
      improve identification. In all three experiments, exposure to a target alongside
      similar comparators failed to support selection of the target from novel test
      stimuli to a greater degree than exposure alongside dissimilar comparators or
      repeated target exposure alone. The current results suggest that the facilitatory
      effects of comparison during exposure may be limited to improving discrimination
      between exposed stimuli, and thus our results do not support the idea that
      providing the opportunity for comparison is a practical means for improving face
      identification. 

PMID- 25590576
TI  - System model network for adipose tissue signatures related to weight changes in
      response to calorie restriction and subsequent weight maintenance.
AB  - Nutrigenomics investigates relationships between nutrients and all genome-encoded
      molecular entities. This holistic approach requires systems biology to scrutinize
      the effects of diet on tissue biology. To decipher the adipose tissue (AT)
      response to diet induced weight changes we focused on key molecular (lipids and
      transcripts) AT species during a longitudinal dietary intervention. To obtain a
      systems model, a network approach was used to combine all sets of variables (bio
      clinical, fatty acids and mRNA levels) and get an overview of their interactions.
      AT fatty acids and mRNA levels were quantified in 135 obese women at baseline,
      after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight
      maintenance diet (WMD). After LCD, individuals were stratified a posteriori
      according to weight change during WMD. A 3 steps approach was used to infer a
      global model involving the 3 sets of variables. It consisted in inferring intra
      omic networks with sparse partial correlations and inter-omic networks with
      regularized canonical correlation analysis and finally combining the obtained
      omic-specific network in a single global model. The resulting networks were
      analyzed using node clustering, systematic important node extraction and cluster
      comparisons. Overall, AT showed both constant and phase-specific biological
      signatures in response to dietary intervention. AT from women regaining weight
      displayed growth factors, angiogenesis and proliferation signaling signatures,
      suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong
      positive relationship between AT myristoleic acid (a fatty acid with low AT
      level) content and de novo lipogenesis mRNAs was found. This relationship was
      also observed, after WMD, in the group of women that continued to lose weight.
      This original system biology approach provides novel insight in the AT response
      to weight control by highlighting the central role of myristoleic acid that may
      account for the beneficial effects of weight loss. 

PMID- 25590577
TI  - Efficacy of oleylphosphocholine (OlPC) in vitro and in a mouse model of invasive
      aspergillosis.
AB  - Invasive aspergillosis (IA) has become increasingly common and is characterised
      by high morbidity and mortality. Upcoming resistance threatens treatment with
      azoles and highlights the continuous need for novel therapeutics. This laboratory
      study investigated the in vitro and in vivo potential of the alkylphospholipid
      oleylphosphocholine (OlPC) against Aspergillus. In vitro activities of OlPC,
      miltefosine, posaconazole and voriconazole were determined for Aspergillus
      fumigatus, A. niger, A. terreus and A. flavus. In vivo efficacy of OlPC was
      evaluated in a systemic A. fumigatus mouse model, adopting a short-term and long
      term oral or intraperitoneal dosing regimen. OlPC showed good in vitro activity
      against A. fumigatus (IC50 = 1.04 MUmol l(-1)). Intraperitoneal administration of
      50 mg kg(-1) day(-1) OlPC significantly reduced the fungal organ burdens at 4
      days post-infection (dpi). Although 5- and 10-day OlPC treatment improved
      survival, organ burdens were not affected at 10 and 15 dpi. While this study
      showed excellent in vitro activity of OlPC against Aspergillus spp., its
      therapeutic efficacy in an acute mouse model for IA was less convincing. Given
      the limited therapeutic options in the current antifungal market for invasive
      infections, OlPC activity should be assessed in a less stringent in vivo model,
      potentially in combination treatment with other already marketed antifungal
      drugs.

PMID- 25590578
TI  - Vanadium-catalyzed regioselective oxidative coupling of 2-hydroxycarbazoles.
AB  - The first regioselective oxidative coupling of 2-hydroxycarbazoles is described.
      With a vanadium catalyst and oxygen as the terminal oxidant, dimers with an ortho
      ortho' coupling pattern were obtained with high selectivity. Further oxidation
      led to ortho'-ortho' coupling to generate a tetramer, which provided insight that
      the atropisomerization barriers of the unsymmetrical biaryl bonds are much lower
      than expected. 

PMID- 25590579
TI  - eIF2 kinases mediate beta-lapachone toxicity in yeast and human cancer cells.
AB  - beta-Lapachone (beta-lap) is a novel anticancer agent that selectively induces
      cell death in human cancer cells, by activation of the NQO1 NAD(P)H dehydrogenase
      and radical oxygen species (ROS) generation. We characterized the gene expression
      profile of budding yeast cells treated with beta-lap using cDNA microarrays.
      Genes involved in tolerance to oxidative stress were differentially expressed in
      beta-lap treated cells. beta-lap treatment generated reactive oxygen species
      (ROS), which were efficiently blocked by dicoumarol, an inhibitor of NADH
      dehydrogenases. A yeast mutant in the mitochondrial NADH dehydrogenase Nde2p was
      found to be resistant to beta-lap treatment, despite inducing ROS production in a
      WT manner. Most interestingly, DNA damage responses triggered by beta-lap were
      abolished in the nde2Delta mutant. Amino acid biosynthesis genes were also
      induced in beta-lap treated cells, suggesting that beta-lap exposure somehow
      triggered the General Control of Nutrients (GCN) pathway. Accordingly, beta-lap
      treatment increased phosphorylation of eIF2alpha subunit in a manner dependent on
      the Gcn2p kinase. eIF2alpha phosphorylation required Gcn1p, Gcn20p and Nde2p.
      Gcn2p was also required for cell survival upon exposure to beta-lap and to elicit
      checkpoint responses. Remarkably, beta-lap treatment increased phosphorylation of
      eIF2alpha in breast tumor cells, in a manner dependent on the Nde2p ortholog AIF,
      and the eIF2 kinase PERK. These findings uncover a new target pathway of beta-lap
      in yeast and human cells and highlight a previously unknown functional connection
      between Nde2p, Gcn2p and DNA damage responses.

PMID- 25590580
TI  - Frequent amplification of PTP1B is associated with poor survival of gastric
      cancer patients.
AB  - The protein tyrosine phosphatase 1B (PTP1B), a non-transmembrane protein tyrosine
      phosphatase, has been implicated in gastric pathogenesis. Several lines of recent
      evidences have shown that PTP1B is highly amplified in breast and prostate
      cancers. The aim of this study was to investigate PTP1B amplification in gastric
      cancer and its association with poor prognosis of gastric cancer patients, and
      further determine the role of PTP1B in gastric tumorigenesis. Our data
      demonstrated that PTP1B was significantly up-regulated in gastric cancer tissues
      as compared with matched normal gastric tissues by using quantitative RT-PCR (qRT
      PCR) assay. In addition, copy number analysis showed that PTP1B was amplified in
      68/131 (51.9%) gastric cancer cases, whereas no amplification was found in the
      control subjects. Notably, PTP1B amplification was positively associated with its
      protein expression, and was significantly related to poor survival of gastric
      cancer patients. Knocking down PTP1B expression in gastric cancer cells
      significantly inhibited cell proliferation, colony formation, migration and
      invasion, and induced cell cycle arrested and apoptosis. Mechanically, PTP1B
      promotes gastric cancer cell proliferation, survival and invasiveness through
      modulating Src-related signaling pathways, such as Src/Ras/MAPK and
      Src/phosphatidylinositol-3-kinase (PI3K)/Akt pathways. Collectively, our data
      demonstrated frequent overexpression and amplification PTP1B in gastric cancer,
      and further determined the oncogenic role of PTP1B in gastric carcinogenesis.
      Importantly, PTP1B amplification predicts poor survival of gastric cancer
      patients. 

PMID- 25590582
TI  - Capillary blood flow imaging within human finger cuticle using optical
      microangiography.
AB  - We report non-invasive 3D imaging of capillary blood flow within human finger
      cuticle by the use of Doppler optical microangiography (DOMAG) and ultra-high
      sensitive optical microangiography (UHS-OMAG) techniques. Wide velocity range
      DOMAG method is applied to provide red blood cell (RBC) axial velocity mapping in
      capillary loops with ranges of +/-0.9 mm/s and +/-0.3 mm/s. Additionally, UHS
      OMAG technique is engineered to acquire high resolution image of capillary
      morphology. The presented results are promising to facilitate clinical trials of
      treatment and diagnosis of various diseases such as diabetes, Raynaud's
      phenomenon, and connective tissue diseases by quantifying cutaneous blood flow
      changes within human finger cuticle.

PMID- 25590581
TI  - GITR intrinsically sustains early type 1 and late follicular helper CD4 T cell
      accumulation to control a chronic viral infection.
AB  - CD4 T cells are critical for control of persistent infections; however, the key
      signals that regulate CD4 T help during chronic infection remain incompletely
      defined. While several studies have addressed the role of inhibitory receptors
      and soluble factors such as PD-1 and IL-10, significantly less work has addressed
      the role of T cell co-stimulatory molecules during chronic viral infection. Here
      we show that during a persistent infection with lymphocytic choriomeningitis
      virus (LCMV) clone 13, mice lacking the glucocorticoid-induced tumor necrosis
      factor receptor related protein (GITR) exhibit defective CD8 T cell accumulation,
      increased T cell exhaustion and impaired viral control. Differences in CD8 T
      cells and viral control between GITR+/+ and GITR-/- mice were lost when CD4 T
      cells were depleted. Moreover, mixed bone marrow chimeric mice, as well as
      transfer of LCMV epitope-specific CD4 or CD8 T cells, demonstrated that these
      effects of GITR are largely CD4 T cell-intrinsic. GITR is dispensable for initial
      CD4 T cell proliferation and differentiation, but supports the post-priming
      accumulation of IFNgamma+IL-2+ Th1 cells, facilitating CD8 T cell expansion and
      early viral control. GITR-dependent phosphorylation of the p65 subunit of NF
      kappaB as well as phosphorylation of the downstream mTORC1 target, S6 ribosomal
      protein, were detected at day three post-infection (p.i.), and defects in CD4 T
      cell accumulation in GITR-deficient T cells were apparent starting at day five
      p.i. Consistently, we pinpoint IL-2-dependent CD4 T cell help for CD8 T cells to
      between days four and eight p.i. GITR also increases the ratio of T follicular
      helper to T follicular regulatory cells and thereby enhances LCMV-specific IgG
      production. Together, these findings identify a CD4 T cell-intrinsic role for
      GITR in sustaining early CD8 and late humoral responses to collectively promote
      control of chronic LCMV clone 13 infection. 

PMID- 25590584
TI  - Catalysts for RNA and DNA modification.
AB  - To study DNAs and RNAs it is often necessary to chemically modify them. Nature's
      strategy for nucleic acid modification is to use selective catalysts, and
      chemists have begun to emulate this conceptual approach. In this review we
      present a summary of catalytic approaches toward the construction of modified
      RNAs and DNAs and outline our opinions on where new research is needed. 

PMID- 25590585
TI  - Dual role of Rh(III) catalyst enables regioselective halogenation of (electron
      rich) heterocycles.
AB  - The Rh(III)-catalyzed selective bromination and iodination of electron-rich
      heterocycles is reported. Kinetic investigations show that Rh plays a dual role
      in the bromination, catalyzing the directed halogenation and preventing the
      inherent halogenation of these substrates. As a result, this method gives highly
      selective access to valuable halogenated heterocycles with regiochemistry
      complementary to those obtained using uncatalyzed approaches, which rely on the
      inherent reactivity of these classes of substrates. Furans, thiophenes,
      benzothiophenes, pyrazoles, quinolones, and chromones can be applied. 

PMID- 25590583
TI  - Breast cancer genes PSMC3IP and EPSTI1 play a role in apoptosis regulation.
AB  - A key element to delineate the biology of individual tumors is the regulation of
      apoptosis. In this work, we functionally characterize two breast cancer
      associated genes, the proteasome 26S subunit ATPase 3 interacting protein
      (PSMC3IP) and the epithelial-stromal interaction 1 (EPSTI1), to explore their
      potential apoptotic role in breast cancer. We first explore the existence of
      direct physical interactions with annotated BC-apoptotic genes. Based on the
      generated interaction network, we examine several apoptotic markers to determine
      the effect of PSMC3IP and EPSTI1 gene expression modulation in two different
      human breast cancer cell lines to suggest potential molecular mechanisms to
      unveil their role in the disease. Our results show that PSMC3IP and EPSTI1 are
      able to modulate the extrinsic apoptotic pathway in estrogen receptor positive
      and triple negative breast cancer cell lines, highlighting them as potential
      therapeutic targets. 

PMID- 25590586
TI  - A clinical and molecular analysis of branchio-oculo-facial syndrome patients in
      Russia revealed new mutations in TFAP2A.
AB  - Branchio-oculo-facial syndrome (BOFS, OMIM# 113620) is a rare autosomal dominant
      disorder characterised by branchial cleft sinus defects, ocular anomalies and
      facial dysmorphisms, including lip or palate cleft or pseudocleft, and is
      associated with mutations in the TFAP2A gene. Here, we performed clinical
      analysis and mutation diagnostics in seven BOFS patients in Russia. The
      phenotypic presentation of BOFS observed in three patients showed high
      heterogeneity, including variation in its main clinical manifestations (linear
      loci of cervical cutaneous aplasia, ocular anomalies and orofacial cleft). In
      certain other cases, isolated ocular anomalies, or an orofacial cleft with
      accessory BOFS symptoms, were observed. In five BOFS patients, conductive hearing
      loss was diagnosed. Direct sequencing of the coding region of the TFAP2A gene
      revealed missense mutations in four BOFS patients. One patient was observed to
      have a previously described mutation (p.Arg251Gly), while three patients from two
      families were found to have novel mutations: p.Arg213Ser and p.Val210Asp. These
      novel mutations were not present in healthy members of the same family and
      therefore should be classified as de novo. 

PMID- 25590588
TI  - Presence, species distribution, and density of Malassezia yeast in patients with
      seborrhoeic dermatitis - a community-based case-control study and review of
      literature.
AB  - Malassezia yeast belongs to the normal cutaneous flora and under certain
      conditions it causes seborrhoeic dermatitis (SD). There is no culture-based study
      about the presence and density of the Malassezia in SD patients in Serbia. Aim
      was to show the presence, species distribution and density of Malassezia in
      patients with SD on lesional skin (LS) and non-lesional skin (NLS) and healthy
      controls (HC) and to compare data between Serbia and other countries. The study
      included 70 HC and 60 patients with SD in the study group (SG). Isolation,
      identification and examination of density of Malassezia colony-forming units from
      LS and NLS were performed. Malassezia was found more frequently in the SG than in
      HC, 90% and 60%, respectively (P < 0.01). The most frequent isolates in SG on LS
      were M. slooffiae (26%), followed by M. globosa (17%) and M. sympodialis (17%).
      The yeast density was much higher on LS of SG than on NLS of SG or in the HC
      group (P < 0.05). Higher density of Malassezia was shown on LS of SG than on NLS
      of SG and HC. M. slooffiae is the most prevalent species in SD patients in
      Serbia. This study demonstrated a positive relationship between severity of SD
      and presence of Malassezia spp. 

PMID- 25590587
TI  - Characterization of Plasmodium ovale curtisi and P. ovale wallikeri in Western
      Kenya utilizing a novel species-specific real-time PCR assay.
AB  - BACKGROUND: Plasmodium ovale is comprised of two genetically distinct subspecies,
      P. ovale curtisi and P. ovale wallikeri. Although P. ovale subspecies are similar
      based on morphology and geographical distribution, allelic differences indicate
      that P. ovale curtisi and P. ovale wallikeri are genetically divergent.
      Additionally, potential clinical and latency duration differences between P.
      ovale curtisi and P. ovale wallikeri demonstrate the need for investigation into
      the contribution of this neglected malaria parasite to the global malaria burden.
      METHODS: In order to detect all P. ovale subspecies simultaneously, we developed
      an inclusive P. ovale-specific real-time PCR assay based on conserved regions
      between P. ovale curtisi and P. ovale wallikeri in the reticulocyte binding
      protein 2 (rbp2) gene. Additionally, we characterized the P. ovale subspecies
      prevalence from 22 asymptomatic malaria infections using multilocus genotyping to
      discriminate P. ovale curtisi and P. ovale wallikeri. RESULTS: Our P. ovale rbp2
      qPCR assay validation experiments demonstrated a linear dynamic range from 6.25
      rbp2 plasmid copies/microliter to 100,000 rbp2 plasmid copies/microliter and a
      limit of detection of 1.5 rbp2 plasmid copies/microliter. Specificity experiments
      showed the ability of the rbp2 qPCR assay to detect low-levels of P. ovale in the
      presence of additional malaria parasite species, including P. falciparum, P.
      vivax, and P. malariae. We identified P. ovale curtisi and P. ovale wallikeri in
      Western Kenya by DNA sequencing of the tryptophan-rich antigen gene, the small
      subunit ribosomal RNA gene, and the rbp2 gene. CONCLUSIONS: Our novel P. ovale
      rbp2 qPCR assay detects P. ovale curtisi and P. ovale wallikeri simultaneously
      and can be utilized to characterize the prevalence, distribution, and burden of
      P. ovale in malaria endemic regions. Using multilocus genotyping, we also
      provided the first description of the prevalence of P. ovale curtisi and P. ovale
      wallikeri in Western Kenya, a region holoendemic for malaria transmission.

PMID- 25590589
TI  - Incubation temperature influences trade-off between structural size and energy
      reserves in mallard hatchlings.
AB  - The reproductive success of precocial birds depends on investments in clutch
      formation and incubation. Egg quality strongly affects the phenotypic traits
      correlated with survival of the hatchling, but parental ability to maintain
      incubation temperature can also influence hatchling outcomes. The effect of
      incubation temperature on hatchling phenotype has been widely studied in reptiles
      but not in birds. The aim of this study was to explore the effects of egg mass
      and incubation temperature on the incubation period, hatchability, and hatchling
      phenotype of the mallard (Anas platyrhynchos). Mallard eggs were incubated under
      six constant incubation temperatures (ranging from 35.0 degrees  to 39.0 degrees
      C). Hatchlings were weighed, and their structural size was measured. Some
      hatchlings were used for an examination of residual yolk sac mass and basic
      chemical composition of the yolk-free body. All investigated phenotypic traits
      except for chemical composition were positively correlated with egg mass.
      Incubation temperature did not affect hatchling body mass, but increased
      temperatures led to a decreased yolk-free body mass and structural size of
      hatchlings and to increased yolk sac mass. Our results suggest that there is a
      trade-off between the yolk-free body size and energetic reserves in the form of
      the yolk sac and that this trade-off is modulated by incubation temperature.

PMID- 25590590
TI  - Epaulet size and current condition in red-winged blackbirds: examining a
      semistatic signal, testosterone, immune function, and parasites.
AB  - Some sexually selected signals are thought to convey information about the
      current condition and genetic/epigenetic quality of the individual signaling,
      including the ability to resist parasites. However, it is unclear whether
      semistatic sexual signals that develop periodically and remain stable over
      protracted periods, such as avian breeding plumage, can relate to measures of
      current condition and health. We examined a semistatic signal (wing epaulet size)
      in male red-winged blackbirds (Agelaius phoeniceus) during the breeding season
      and looked for relationships between this trait and circulating testosterone (T),
      hematocrit, bacteria-killing ability (BKA) of the blood, and the infection
      status, richness, and abundance of four functional categories of parasite. We
      found that epaulet size was positively related to circulating levels of T and
      ectoparasite infections. We found no relationships between T and parasite
      infections. In adult males there was a negative relationship between T and BKA,
      whereas in yearling males there was no relationship. We found no evidence for a
      general reduction in immunocompetence in males with larger epaulets but rather an
      increase in susceptibility to specific types of parasites. Our results suggest
      that semistatic signals can be linked to measures of current condition, and we
      postulate that these relationships are modulated via activity levels related to
      breeding-season activities.

PMID- 25590591
TI  - Effect of nutritional status on the osmoregulation of green sturgeon (Acipenser
      medirostris).
AB  - Anthropogenic climate change is linked to food web and salinity fluctuations in
      estuarine environments. Both decreased nutritional status and environmental
      salinity influence the physiological tolerance and health of fish populations;
      however, limited information on the interaction of these two factors and their
      physiological consequences is available. The green sturgeon (Acipenser
      medirostris) is a species of special concern in California, and the southern
      distinct population segment is listed as threatened. To test the hypothesis that
      poor nutrition negatively affects osmoregulation, juvenile green sturgeon (222 d
      posthatch) were randomly assigned to four feed restriction groups (12.5%, 25%,
      50%, and 100% of the optimal feeding rate for 4 wk). Fish were then acutely
      exposed to 0-, 8-, 16-, or 32-ppt salinities and sampled at three time points
      (12, 72, or 120 h). Feed restriction significantly (P < 0.05) decreased specific
      growth rate, feed efficiency, condition factor, whole-body lipids, and protein
      content as well as plasma glucose, triglycerides, and proteins. Furthermore, feed
      restriction, salinity concentration, and salinity exposure time had significant
      effects on hematological indexes (hematocrit, hemoglobin), plasma values
      (osmolality, Na(+), K(+), Cl(-), glucose, lactate, cortisol), enzymatic activity
      (gill and pyloric ceca Na(+)/K(+) ATPase), and morphology of gill mitochondria
      rich cells. The largest disturbances were observed at the highest salinity
      treatments across all feeding regimes. In addition, the interaction between feed
      restriction and acute salinity exposure at the highest salinity treatment
      resulted in high mortality rates during the first 72 h of salinity exposure.
      Evaluating the interactions of these environmental stressors and their
      implications on green sturgeon physiological tolerance will inform restoration
      and management efforts in rapidly changing estuarine environments.

PMID- 25590592
TI  - Metabolomic differentiation of nutritional stress in an aquatic invertebrate.
AB  - Poor diet quality frequently constrains the growth and reproduction of primary
      consumers, altering their population dynamics, interactions in food webs, and
      contributions to ecosystem services such as nutrient cycling. The identification
      and measurement of an animal's nutritional state are thus central to studying the
      connections between diet and animal ecology. Here we show how the nutritional
      state of a freshwater invertebrate, Daphnia magna, can be determined by analyzing
      its endogenous metabolites using hydrogen nuclear magnetic resonance-based
      metabolomics. With a multivariate analysis, we observed the differentiation of
      the metabolite composition of animals grown under control conditions (good food
      and no environmental stress), raised on different diets (low quantity, nitrogen
      limited, and phosphorus limited), and exposed to two common environmental
      stressors (bacterial infection and salt stress). We identified 18 metabolites
      that were significantly different between control animals and at least one
      limiting food type or environmental stressor. The unique metabolite responses of
      animals caused by inadequate nutrition and environmental stress are reflective of
      dramatic and distinctive effects that each stressor has on animal metabolism. Our
      results suggest that dietary-specific induced changes in metabolite composition
      of animal consumers hold considerable promise as indicators of nutritional stress
      and will be invaluable to future studies of animal nutrition.

PMID- 25590593
TI  - Effects of starvation and molting on the metabolic rate of the bed bug (Cimex
      lectularius L.).
AB  - The bed bug (Cimex lectularius L.) is a common hematophagous pest in the urban
      environment and is capable of surviving extended periods of starvation. However,
      the relationship between starvation and metabolism in bed bugs is not well
      understood. To better understand this relationship, we measured the metabolism of
      all life stages for >900 h after feeding (starvation) using closed-system
      respirometry. Measurements were made around molting for the immature life stages,
      which occurs only after a blood meal. In addition, both mated and unmated adults
      were measured. Starvation and molting had significant effects on the metabolism
      of the bed bug. Mass-specific metabolic rate (V(O2); mL g(-1) h(-1)) declined in
      a curvilinear fashion with the period of starvation for adults and with the
      postmolting period for immature bed bugs (used to standardize all immature life
      stages). A standard curve was developed to depict the generalized pattern of
      metabolic decline observed in all life stages that molted. Individual metabolic
      comparisons among life stages that molted revealed some differences in metabolic
      rate between unmated males and females. In addition, the mass scaling coefficient
      was found to decline with starvation time (postmolting time) for all life stages
      that molted. In most life stages, the ratio of V(CO2) to V(O2) (respiratory
      exchange ratio) declined over time, indicating a change in metabolic substrate
      with starvation. Finally, daily percent loss in body mass declined in a pattern
      similar to that of V(O2). The observed patterns in metabolic decline are
      evaluated in relation to the life history of bed bugs. In addition, the
      evolutionary development of these patterns is discussed. The metabolic pattern
      after feeding was also found to share several similarities with that of other
      ectothermic species.

PMID- 25590594
TI  - Natural variation in resistance to desiccation and heat shock protein expression
      in the land snail Theba pisana along a climatic gradient.
AB  - Land snails frequently encounter desiccating conditions, and their survival
      depends on a suite of morphological, physiological, and molecular adaptations to
      the specific microhabitat. Strategies of survival can be determined by
      integrating information from various levels of biological organization. In this
      study, we used a combination of physiological parameters related to water economy
      and molecular factors (stress protein expression) to investigate the strategies
      of survival adopted by seven populations of the Mediterranean-type land snail
      Theba pisana from different habitats. We analyzed water compartmentalization
      during aestivation and used experimental desiccation to compare desiccation
      resistance. We also measured the endogenous levels of heat shock proteins (HSPs)
      Hsp72, Hsp74, and Hsp90 under nonstress conditions and analyzed the HSP response
      to desiccation in two populations that differed mostly in their resistance to
      desiccation. We revealed significant intraspecific differences in resistance to
      desiccation that seem to be determined by the speed of recruitment of the water
      preserving mechanisms. The ability to cope with desiccating conditions was
      correlated with habitat temperature but not with the rainfall gradient, implying
      that in the coastal region, temperature is likely to have a major impact on
      desiccation resistance rather than precipitation. Also, higher desiccation
      resistance was correlated with higher constitutive levels of Hsp74 in the foot
      tissue. HSPs were upregulated during desiccation, but the response was delayed
      and was milder in the most resistant population compared to the most susceptible
      one. Our study suggests that T. pisana populations from warmer habitats were more
      resistant to desiccation and developed distinct strategies of HSP expression for
      survival, namely, the maintenance of high constitutive levels of Hsp70 together
      with a delayed and limited response to stress.

PMID- 25590595
TI  - Thermogenic capacity at subzero temperatures: how low can a hibernator go?
AB  - Abstract Hibernation in mammals is a physiological and behavioral adaptation to
      survive intervals of low resource availability through profound decreases in
      metabolic rate (MR), core body temperature (Tb), and activity. Most small
      mammalian hibernators thermoconform, with Tb approximating ambient temperature
      (Ta); arctic species are an exception, since they must actively defend what can
      be large thermal gradients between Tb and Ta. Here we compare the thermogenic
      capacity of the arctic ground squirrel (Urocitellus parryii) to that of the
      golden-mantled ground squirrel (Callospermophilus lateralis), a temperate-zone
      montane hibernator. We allowed animals to reenter torpor at sequentially lower
      Ta's and found that arctic ground squirrels maintained steady state torpor at
      Ta's as low as -26 degrees C, through a 36-fold increase in torpid MR (TMR),
      compared to their minimum TMR, exhibited at a Ta of 0 degrees C. Golden-mantled
      ground squirrels are able to maintain steady state torpor at Ta's at least as low
      as -8 degrees C, through a 13.5-fold increase in MR, compared to their minimum
      TMR at a Ta of 2 degrees C. In a second experiment, torpid animals were exposed
      to continuously decreasing Ta's (0.25 degrees C/30 min); individuals of both
      species increased their metabolism while remaining torpid at low Ta's (as low as 
      30 degrees C for arctic ground squirrels and -10 degrees C for golden-mantled
      ground squirrels). Although the capacity to hibernate at subfreezing Ta's is not
      unique to arctic ground squirrels, their large body size, greater torpid
      metabolic scope, and previously ascribed capacity to supercool allow them to
      occupy much colder hibernacula for prolonged seasons of hibernation. 

PMID- 25590596
TI  - Microsatellite alterations are also present in the less aggressive types of adult
      T-cell leukemia-lymphoma.
AB  - BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasia
      etiologically linked to HTLV-1. Manifestations of ATL are diverse and different
      clinical types with different tissue involvement and aggressiveness have been
      described. The mechanisms that lead to the development of ATL clinical types have
      not yet been clarified. Considering that in ATL patients HTLV-1 infection
      generally occurs in childhood, a multistep carcinogenesis model has been
      proposed. Microsatellite alterations are important genetic events in cancer
      development and these alterations have been reported in the aggressive types of
      ATL. Little is known about oncogenesis of the less aggressive types.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the role of the
      microsatellite alterations in the pathogenesis mediated by HTLV-1 in the
      different types of ATL. We examined the presence of microsatellite instability
      (MSI) and loss of heterozigosity (LOH) in matched pair samples (tumoral and
      normal) of 24 patients with less aggressive types (smoldering and chronic) and in
      aggressive types (acute and lymphoma) of ATL. Four microsatellite markers
      D10S190, D10S191, D1391 and DCC were analyzed. MSI was found in four patients,
      three smoldering and one chronic, and LOH in four patients, three smoldering and
      one acute. None of the smoldering patients with microsatellite alterations
      progressed to aggressive ATL. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is
      the first report describing the presence of MSI and LOH in the less aggressive
      types of ATL. These results indicate that microsatellite alterations may
      participate in the development of the less aggressive types of ATL.

PMID- 25590597
TI  - Thyroid-stimulating hormone inhibits adipose triglyceride lipase in 3T3-L1
      adipocytes through the PKA pathway.
AB  - Thyroid-stimulating hormone (TSH) has been shown to play an important role in the
      regulation of triglyceride (TG) metabolism in adipose tissue. Adipose
      triglyceride lipase (ATGL) is a rate-limiting enzyme controlling the hydrolysis
      of TG. Thus far, it is unclear whether TSH has a direct effect on the expression
      of ATGL. Because TSH function is mediated through the TSH receptor (TSHR), TSHR
      knockout mice (Tshr-/- mice) (supplemented with thyroxine) were used in this
      study to determine the effects of TSHR deletion on ATGL expression. These effects
      were verified in 3T3-L1 adipocytes and potential underlying mechanisms were
      explored. In the Tshr-/- mice, ATGL expression in epididymal adipose tissue was
      significantly increased compared with that in Tshr+/+ mice. ATGL expression was
      observed to increase with the differentiation process of 3T3-L1 preadipocytes. In
      mature 3T3-L1 adipocytes, TSH significantly suppressed ATGL expression at both
      the protein and mRNA levels in a dose-dependent manner. Forskolin, which is an
      activator of adenylate cyclase, suppressed the expression of ATGL in 3T3-L1
      adipocytes. The inhibitory effects of TSH on ATGL expression were abolished by
      H89, which is a protein kinase A (PKA) inhibitor. These results indicate that TSH
      has an inhibitory effect on ATGL expression in mature adipocytes. The associated
      mechanism is related to PKA activation.

PMID- 25590598
TI  - Effect of cause-of-death training on agreement between hospital discharge
      diagnoses and cause of death reported, inpatient hospital deaths, New York City,
      2008-2010.
AB  - INTRODUCTION: Accurate cause-of-death reporting is required for mortality data to
      validly inform public health programming and evaluation. Research demonstrates
      overreporting of heart disease on New York City death certificates. We describe
      changes in reported causes of death following a New York City health department
      training conducted in 2009 to improve accuracy of cause-of-death reporting at 8
      hospitals. The objective of our study was to assess the degree to which death
      certificates citing heart disease as cause of death agreed with hospital
      discharge data and the degree to which training improved accuracy of reporting.
      METHODS: We analyzed 74,373 death certificates for 2008 through 2010 that were
      linked with hospital discharge records for New York City inpatient deaths and
      calculated the proportion of discordant deaths, that is, death certificates
      reporting an underlying cause of heart disease with no corresponding discharge
      record diagnosis. We also summarized top principal diagnoses among discordant
      reports and calculated the proportion of inpatient deaths reporting sepsis, a
      condition underreported in New York City, to assess whether documentation
      practices changed in response to clarifications made during the intervention.
      RESULTS: Citywide discordance between death certificates and discharge data
      decreased from 14.9% in 2008 to 9.6% in 2010 (P < .001), driven by a decrease in
      discordance at intervention hospitals (20.2% in 2008 to 8.9% in 2010; P < .001).
      At intervention hospitals, reporting of sepsis increased from 3.7% of inpatient
      deaths in 2008 to 20.6% in 2010 (P < .001). CONCLUSION: Overreporting of heart
      disease as cause of death declined at intervention hospitals, driving a citywide
      decline, and sepsis reporting practices changed in accordance with health
      department training. Researchers should consider the effect of overreporting and
      data-quality changes when analyzing New York City heart disease mortality trends.
      Other vital records jurisdictions should employ similar interventions to improve
      cause-of-death reporting and use linked discharge data to monitor data quality.

PMID- 25590599
TI  - Administrative data linkage to evaluate a quality improvement program in acute
      stroke care, Georgia, 2006-2009.
AB  - INTRODUCTION: Tracking the vital status of stroke patients through death data is
      one approach to assessing the impact of quality improvement in stroke care. We
      assessed the feasibility of linking Georgia hospital discharge data with
      mortality data to evaluate the effect of participation in the Georgia Coverdell
      Acute Stroke Registry on survival rates among acute ischemic stroke patients.
      METHODS: Multistage probabilistic matching, using a fine-grained record
      integration and linkage software program and combinations of key variables, was
      used to link Georgia hospital discharge data for 2005 through 2009 with mortality
      data for 2006 through 2010. Data from patients admitted with principal diagnoses
      of acute ischemic stroke were analyzed by using the extended Cox proportional
      hazard model. The survival times of patients cared for by hospitals participating
      in the stroke registry and of those treated at nonparticipating hospitals were
      compared. RESULTS: Average age of the 50,579 patients analyzed was 69 years, and
      56% of patients were treated in Georgia Coverdell Acute Stroke Registry
      hospitals. Thirty-day and 365-day mortality after first admission for stroke were
      8.1% and 18.5%, respectively. Patients treated at nonparticipating facilities had
      a hazard ratio for death of 1.14 (95% confidence interval, 1.03-1.26; P = .01)
      after the first week of admission compared with patients cared for by hospitals
      participating in the registry. CONCLUSION: Hospital discharge data can be linked
      with death data to assess the impact of clinical-level or community-level chronic
      disease control initiatives. Hospitals need to undertake quality improvement
      activities for a better patient outcome.

PMID- 25590600
TI  - Behavioral economics: "nudging" underserved populations to be screened for
      cancer.
AB  - Persistent disparities in cancer screening by race/ethnicity and socioeconomic
      status require innovative prevention tools and techniques. Behavioral economics
      provides tools to potentially reduce disparities by informing strategies and
      systems to increase prevention of breast, cervical, and colorectal cancers. With
      an emphasis on the predictable, but sometimes flawed, mental shortcuts
      (heuristics) people use to make decisions, behavioral economics offers insights
      that practitioners can use to enhance evidence-based cancer screening
      interventions that rely on judgments about the probability of developing and
      detecting cancer, decisions about competing screening options, and the optimal
      presentation of complex choices (choice architecture). In the area of judgment,
      we describe ways practitioners can use the availability and representativeness of
      heuristics and the tendency toward unrealistic optimism to increase perceptions
      of risk and highlight benefits of screening. We describe how several behavioral
      economic principles involved in decision-making can influence screening
      attitudes, including how framing and context effects can be manipulated to
      highlight personally salient features of cancer screening tests. Finally, we
      offer suggestions about ways practitioners can apply principles related to choice
      architecture to health care systems in which cancer screening takes place. These
      recommendations include the use of incentives to increase screening, introduction
      of default options, appropriate feedback throughout the decision-making and
      behavior completion process, and clear presentation of complex choices,
      particularly in the context of colorectal cancer screening. We conclude by noting
      gaps in knowledge and propose future research questions to guide this promising
      area of research and practice. 

PMID- 25590602
TI  - Identification and validation of long noncoding RNA biomarkers in human non-small
      cell lung carcinomas.
AB  - INTRODUCTION: Dysregulation of long noncoding RNAs (lncRNAs) has been regarded as
      a primary feature of several human cancers. However, the genome-wide expression
      and functional significance of lncRNAs in non-small-cell lung carcinomas (NSCLC)
      remains unclear. The aim of this study was to identify novel lncRNAs that may
      play an important role in contributing to NSCLC pathogenesis. METHODS: We
      performed an integrative analysis of two NSCLC microarray datasets comprising 165
      and 90 patients, respectively. The candidate lncRNAs were identified using the
      GSE19188 dataset, and then confirmed in the GSE18842 dataset. In addition, an
      independent cohort of 73 clinical samples was analyzed to validate the selected
      lncRNAs by quantitative real-time polymerase chain reaction analysis. RESULTS:
      With microarray gene expression analysis, we identified and validated a list of
      64 lncRNAs significantly dysregulated in NSCLC tumors compared with normal lung
      tissues; and a panel of 181 lncRNAs that were specific to histological subtypes
      of NSCLC (adenocarcinoma, large-cell carcinoma, and squamous cell carcinoma). The
      quantitative real-time polymerase chain reaction analysis of six selected lncRNAs
      in clinical samples further confirmed the results of microarray analysis.
      CONCLUSIONS: We have identified and validated multiple novel lncRNAs associated
      with tumorigenesis and histological differentiation in human NSCLC. These lncRNAs
      could be further exploited for the development of useful biomarkers in diagnosis,
      prognosis, and treatment of NSCLC.

PMID- 25590601
TI  - Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose.
AB  - The Target Of Rapamycin (TOR) is an evolutionarily conserved protein kinase that
      forms 2 distinct protein complexes referred to as TOR complex 1 (TORC1) and 2
      (TORC2). Recent extensive studies have demonstrated that TORC1 is under the
      control of the small GTPases Rheb and Rag that funnel multiple input signals
      including those derived from nutritional sources; however, information is scarce
      as to the regulation of TORC2. A previous study using the model system provided
      by the fission yeast Schizosaccharomyces pombe identified Ryh1, a Rab-family
      GTPase, as an activator of TORC2. Here, we show that the nucleotide-binding state
      of Ryh1 is regulated in response to glucose, mediating this major nutrient signal
      to TORC2. In glucose-rich growth media, the GTP-bound form of Ryh1 induces TORC2
      dependent phosphorylation of Gad8, a downstream target of TORC2 in fission yeast.
      Upon glucose deprivation, Ryh1 becomes inactive, which turns off the TORC2-Gad8
      pathway. During glucose starvation, however, Gad8 phosphorylation by TORC2
      gradually recovers independently of Ryh1, implying an additional TORC2 activator
      that is regulated negatively by glucose. The paired positive and negative
      regulatory mechanisms may allow fine-tuning of the TORC2-Gad8 pathway, which is
      essential for growth under glucose-limited environment.

PMID- 25590603
TI  - Conditional survival of malignant thymoma using national population-based
      surveillance, epidemiology, and end results (SEER) registry (1973-2011).
AB  - INTRODUCTION: Thymoma is a rare and unique tumor with a long natural history that
      makes it difficult to study. Consequently, there is a dearth of prospective
      diagnostic or therapeutic clinical trials. To our knowledge, there has not been
      an analysis of conditional survival of thymoma in the literature. The specific
      aim of this study was to study the 5-year conditional survivals of a large
      population of thymoma patients. METHODS: Cases of thymoma were extracted from the
      Surveillance, Epidemiology, and End Results registry (1973-2011) and categorized
      into Masaoka-Koga stage groupings. The primary outcomes compared overall survival
      (OS), cause specific survival (CSS), and 5-year conditional OS and CSS, by stage.
      OS and CSS were calculated using the Kaplan-Meier method with the log-rank test
      for significance using SAS v9.3. Conditional survival was the probability of
      surviving an additional 5 years at any point in follow-up, and used analysis of
      variance to test significance. RESULTS: A total of 2182 patients met inclusion
      criteria and were categorized as Masaoka-Koga stage groupings of I and IIA
      ("localized," 24%), IIB ("regional," 16%), III and IV ("distant," 50%), and
      unknown (10%). Median age was 56 (18-91), and 53% were male. Earlier stages had
      better OS (p < 0.0001) and CSS (p < 0.0001). Twenty-year OS for local, regional,
      and distant stages were 42%, 30%, and 18%, respectively. Conditional survivals
      remained largely unchanged throughout follow-up. CONCLUSIONS: Conditional
      survival provides more relevant survival estimates for patients during follow-up.
      Further studies should investigate the possibility that thymoma should be
      considered a chronic disease.

PMID- 25590605
TI  - Relationship between tumor size and survival in non-small-cell lung cancer
      (NSCLC): an analysis of the surveillance, epidemiology, and end results (SEER)
      registry.
AB  - INTRODUCTION: Tumor size is a known prognostic factor for early stage non-small
      cell lung cancer (NSCLC), but its significance in node-positive and locally
      invasive NSCLC has not been extensively characterized. We queried the
      Surveillance, Epidemiology, and End Results database to evaluate the prognostic
      value of tumor size for early stage and node-positive and locally invasive NSCLC.
      METHODS: Patients in Surveillance, Epidemiology, and End Results registry with
      NSCLC diagnosed between 1998 and 2003 were analyzed. Tumor size was analyzed as a
      continuous variable. Other demographic variables included age, gender, race,
      histology, primary tumor extension, node status, and primary treatment modality
      (surgery vs. radiation). The Kaplan-Meier method was used to estimate overall
      survival (OS). Cox proportional hazard model was used to evaluate whether tumor
      size was an independent prognostic factor. RESULTS: In all, 52,287 eligible
      patients were subgrouped based on tumor extension and node status. Tumor size had
      a significant effect on OS in all subgroups defined by tumor extension or node
      status. In addition, tumor size also had statistically significant effect on OS
      in 15 of 16 subgroups defined by tumor extension and nodal status after
      adjustment for other clinical variables. Our model incorporating tumor size had
      significantly better predictive accuracy than our alternative model without tumor
      size. CONCLUSIONS: Tumor size is an independent prognostic factor, for early
      stage and node-positive and locally invasive disease. Prediction tools, such as
      nomograms, incorporating more detailed information not captured in detail by the
      routine tumor, node, metastasis classification, may improve prediction accuracy
      of OS in NSCLC.

PMID- 25590606
TI  - Cost-effectiveness of multiplexed predictive biomarker screening in non-small
      cell lung cancer.
AB  - INTRODUCTION: Population-wide screening for epidermal growth factor receptor
      (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements to
      inform cancer therapy in non-small-cell lung cancer (NSCLC) is recommended by
      guidelines. We estimated cost-effectiveness of multiplexed predictive biomarker
      screening in metastatic NSCLC from a societal perspective in the United States.
      METHODS: We constructed a microsimulation model to compare the life expectancy
      and costs of multiplexed testing and molecularly guided therapy versus treatment
      with cisplatin-pemetrexed (CisPem). All testing interventions included a two-step
      algorithm of concurrent EGFR mutation and ALK overexpression testing with
      immunohistochemistry followed by ALK rearrangement confirmation with a
      fluorescence in situ hybridization assay for immunohistochemistry-positive
      results. Three strategies were included: "Test-treat" approach, where molecularly
      guided therapy was initiated after obtainment of test results; "Empiric switch
      therapy," with concurrent initiation of CisPem and testing and immediate switch
      to test-result conditional treatment after one cycle of CisPem; and "Empiric
      therapy" approach in which CisPem was continued for four cycles before start of a
      tyrosine kinase inhibitor. RESULTS: The incremental cost-effectiveness ratio for
      "Test-treat" compared with treatment with CisPem was $136,000 per quality
      adjusted life year gained. Both empiric treatment approaches had less favorable
      incremental cost-effectiveness ratios. "Test-treat" and "Empiric switch therapy"
      yielded higher expected outcomes in terms of quality-adjusted life years and life
      years than "Empiric therapy." These results were robust across plausible ranges
      of model inputs. CONCLUSION: From a societal perspective, our cost-effectiveness
      results support the value of multiplexed genetic screening and molecularly guided
      therapy in metastatic NSCLC.

PMID- 25590604
TI  - Validation of a multiprotein plasma classifier to identify benign lung nodules.
AB  - INTRODUCTION: Indeterminate pulmonary nodules (IPNs) lack clinical or
      radiographic features of benign etiologies and often undergo invasive procedures
      unnecessarily, suggesting potential roles for diagnostic adjuncts using molecular
      biomarkers. The primary objective was to validate a multivariate classifier that
      identifies likely benign lung nodules by assaying plasma protein expression
      levels, yielding a range of probability estimates based on high negative
      predictive values (NPVs) for patients with 8 to 30 mm IPNs. METHODS: A
      retrospective, multicenter, case-control study was performed using multiple
      reaction monitoring mass spectrometry, a classifier comprising five diagnostic
      and six normalization proteins, and blinded analysis of an independent validation
      set of plasma samples. RESULTS: The classifier achieved validation on 141 lung
      nodule-associated plasma samples based on predefined statistical goals to
      optimize sensitivity. Using a population based nonsmall-cell lung cancer
      prevalence estimate of 23% for 8 to 30 mm IPNs, the classifier identified likely
      benign lung nodules with 90% negative predictive value and 26% positive
      predictive value, as shown in our prior work, at 92% sensitivity and 20%
      specificity, with the lower bound of the classifier's performance at 70%
      sensitivity and 48% specificity. Classifier scores for the overall cohort were
      statistically independent of patient age, tobacco use, nodule size, and chronic
      obstructive pulmonary disease diagnosis. The classifier also demonstrated
      incremental diagnostic performance in combination with a four-parameter clinical
      model. CONCLUSIONS: This proteomic classifier provides a range of probability
      estimates for the likelihood of a benign etiology that may serve as a
      noninvasive, diagnostic adjunct for clinical assessments of patients with IPNs.

PMID- 25590608
TI  - Enhanced reductive dechlorination of tetrachloroethene by nano-sized mackinawite
      with cyanocobalamin in a highly alkaline condition.
AB  - In this study, we characterize the reductive dechlorination of tetrachloroethene
      (PCE) by nano-sized mackinawite (nFeS) with cobalamin (Cbl(III)) at a high pH and
      investigate the effects of environmental factors, including the concentrations of
      the target contaminant, reductant, and catalyst and suspension ions on the
      dechlorination kinetics of PCE. Ninety five percent of the PCE was degraded by
      nFeS with Cbl(III) in 15 h. Cyclic voltammetry conducted with regard to the
      reductive dechlorination showed a higher redox potential of mackinawite under a
      high-pH condition (-1.01 V), suggesting that the oxidation state of the central
      cobalt ion in the cobalamin could be reduced to Cbl(I). The change of cobalamin
      species on the nFeS surface was verified under different pH conditions by UV-vis
      spectroscopy. The rate constant of PCE dechlorination increased from 0.1582 to
      0.4284 h(-1) due to the increase in the nFeS content (2.085-20.85 g/L). As the
      concentration of Cbl(III) increased from 0 to 0.5 mM, the dechlorination kinetics
      of PCE was accelerated (0-1.4091 h(-1)) but reached a state of equilibrium from
      0.5 to 1 mM. The increase in the initial PCE concentration (0.035-1.0 mM) slowed
      down the dechlorination kinetics (0.2036-0.0962 h(-1)). The dechlorination
      kinetics was enhanced by 1.5-11 times when 10 mM of ions (Na(+), K(+), Mg(2+),
      Ca(2+), CO3(2-), SO4(2-), and NO3(-)) were added, while an addition of HCO3
      decelerated it by 10 times. This study can provide background knowledge
      pertaining to the PCE dechlorination by a natural reductant under a high-pH
      condition and the effect of environmental factors on the dechlorination kinetics
      for the development of novel remediation technologies.

PMID- 25590609
TI  - The complexity of biosorption treatments for oxyanions in a multi-element mine
      effluent.
AB  - Selenium (Se) is a contaminant in effluents from coal mines and coal-fired power
      stations, where it is encountered as the oxyanion selenate (SeO4(2-), hereafter
      Se(VI)). Se(VI) can be removed from solution with Fe-treated biosorbents, but the
      efficacy of these treatments in effluents with multiple contaminants is unclear.
      This study investigates the interactions between Se(VI) and the oxyanions SO4(2-)
      and NO3(-). We produce a sustainable biosorbent, Gracilaria Modified Biochar
      (GMB), by treating a waste product generated after the commercial extraction of
      agar from cultivated seaweeds with ferric chloride (FeCl3) and converting it to
      biochar through pyrolysis. We then test interactions between Se(VI) and competing
      oxyanions in mock solutions and a real-world mine effluent with high
      concentrations of SO4(2-) and NO3(-). GMB immediately removed 98% of the Se(VI)
      from the mock solution, but only 3% from the mine effluent with the same initial
      Se(VI) concentration. Notably, 83-89% of the Se(VI) was removed by GMB when
      concentrations of Se(VI) and SO4(2-) were less than or equimolar in mock
      solutions. Higher concentrations of SO4(2-) reduced the uptake of Se(VI). There
      was no interference from NO3(-) on the biosorption of Se(VI). GMB is a successful
      biosorbent for Se(VI), however, high concentrations of SO4(2-) will compromise
      the biosorption of Se(VI).

PMID- 25590611
TI  - Modular continuing professional development for emergency physicians - the MNSHA
      masterclass programme.
AB  - INTRODUCTION: Emergency physician (EP) training in the Netherlands is currently a
      3-year competency-based programme. Upon its completion, many Dutch EPs feel that
      they lack some of the skills and the knowledge necessary to be fully prepared for
      the challenges of emergency medicine. We perceived a need for new methods to
      deliver continuing professional development (CPD). METHODS: A needs analysis
      survey was conducted to ascertain whether our perceived need for a new CPD
      programme was genuine. A new course was developed, incorporating innovative
      learning methods. The results of the needs analysis were incorporated into the
      programme. Another survey was held among participants of the first two editions
      of the programme. RESULTS, DISCUSSION AND CONCLUSION: Modular CPD for Emergency
      Physicians (Dutch: MNSHA) is a modular programme that aims to deliver CPD to
      Dutch EPs. It combines innovative educational methods, such as asynchronous
      learning in a flipped classroom, with web-based mentoring. The aim is for
      participants to develop effective, individualized and sustainable methods to gain
      and maintain knowledge and skills as a part of their ongoing professional
      education. The participant survey showed encouraging results, strongly suggesting
      an improvement in confidence. A more robust study would be required to better
      assess the outcomes of our programme.

PMID- 25590610
TI  - MicroRNA targets: potential candidates for indirect regulation by drugs.
AB  - BACKGROUND: Gene expression is regulated by trans-acting transcription factors
      and microRNAs (miRNAs) through interactions with their respective cis-regulatory
      elements. The effects that drugs induce result from complex interactions in
      pathways downstream from their primary targets. These interactions, from gene
      regulatory apparatus and from drug-induced pathways, form a complex, multilayered
      network. METHODS: Knowing that drugs can perturb miRNA expression profiles, a
      genomewide analysis of drug-induced intronic miRNA perturbations has been
      presented here. RESULTS: By comparative analysis of control and drugged data sets
      from 27 independent gene expression experiments, it was feasible to detect the
      effect of drugs on miRNA target genes. Signatures of 21 of 28 miRNAs, predicted
      to be influenced by drug action, were detected. CONCLUSION: This study
      demonstrates that the action of drugs on mRNA expression can be mediated through
      the combinatorial effects of miRNAs. In addition, transcription factors, through
      miRNAs within the introns of their target genes, can exert an indirect effect on
      the expression of distal mRNAs.

PMID- 25590607
TI  - Discovery of CLC transport proteins: cloning, structure, function and
      pathophysiology.
AB  - After providing a personal description of the convoluted path leading 25 years
      ago to the molecular identification of the Torpedo Cl(-) channel ClC-0 and the
      discovery of the CLC gene family, I succinctly describe the general structural
      and functional features of these ion transporters before giving a short overview
      of mammalian CLCs. These can be categorized into plasma membrane Cl(-) channels
      and vesicular Cl(-) /H(+) -exchangers. They are involved in the regulation of
      membrane excitability, transepithelial transport, extracellular ion homeostasis,
      endocytosis and lysosomal function. Diseases caused by CLC dysfunction include
      myotonia, neurodegeneration, deafness, blindness, leukodystrophy, male
      infertility, renal salt loss, kidney stones and osteopetrosis, revealing a
      surprisingly broad spectrum of biological roles for chloride transport that was
      unsuspected when I set out to clone the first voltage-gated chloride channel. 

PMID- 25590612
TI  - The interaction between seasonality and pulsed interventions against malaria in
      their effects on the reproduction number.
AB  - The basic reproduction number (R0) is an important quantity summarising the
      dynamics of an infectious disease, as it quantifies how much effort is needed to
      control transmission. The relative change in R0 due to an intervention is
      referred to as the effect size. However malaria and other diseases are often
      highly seasonal and some interventions have time-varying effects, meaning that
      simple reproduction number formulae cannot be used. Methods have recently been
      developed for calculating R0 for diseases with seasonally varying transmission. I
      extend those methods to calculate the effect size of repeated rounds of mass drug
      administration, indoor residual spraying and other interventions against
      Plasmodium falciparum malaria in seasonal settings in Africa. I show that if an
      intervention reduces transmission from one host to another by a constant factor,
      then its effect size is the same in a seasonal as in a non-seasonal setting. The
      optimal time of year for drug administration is in the low season, whereas the
      best time for indoor residual spraying or a vaccine which reduces infection rates
      is just before the high season. In general, the impact of time-varying
      interventions increases with increasing seasonality, if carried out at the
      optimal time of year. The effect of combinations of interventions that act at
      different stages of the transmission cycle is roughly the product of the separate
      effects. However for individual time-varying interventions, it is necessary to
      use methods such as those developed here rather than inserting the average
      efficacy into a simple formula. 

PMID- 25590613
TI  - Macrophage activation in acute exacerbation of idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a
      common cause of disease acceleration in IPF and has a major impact on mortality.
      The role of macrophage activation in AE of IPF has never been addressed before.
      METHODS: We evaluated BAL cell cytokine profiles and BAL differential cell counts
      in 71 IPF patients w/wo AE and in 20 healthy volunteers. Twelve patients suffered
      from AE at initial diagnosis while sixteen patients developed AE in the 24 months
      of follow-up. The levels of IL-1ra, CCL2, CCL17, CCL18, CCL22, TNF-alpha, IL
      1beta, CXCL1 and IL-8 spontaneously produced by BAL-cells were analysed by ELISA.
      RESULTS: In patients with AE, the percentage of BAL neutrophils was significantly
      increased compared to stable patients. We found an increase in the production
      rate of the pro-inflammatory cytokines CXCL1 and IL-8 combined with an increase
      in all tested M2 cytokines by BAL-cells. An increase in CCL18 levels and
      neutrophil counts during AE was observed in BAL cells from patients from whom
      serial lavages were obtained. Furthermore, high baseline levels of CCL18
      production by BAL cells were significantly predictive for the development of
      future AE. CONCLUSIONS: BAL cell cytokine production levels at acute exacerbation
      show up-regulation of pro-inflammatory as well as anti-inflammatory/ M2
      cytokines. Our data suggest that AE in IPF is not an incidental event but rather
      driven by cellular mechanisms including M2 macrophage activation.

PMID- 25590616
TI  - Glutamine and antioxidants: status of their use in critical illness.
AB  - PURPOSE OF REVIEW: Many studies in critically ill patients have addressed enteral
      or parenteral supplementation of glutamine and antioxidants to counteract assumed
      deficiencies and induce immune-modulating effects to reduce infections and
      improve outcome. Older studies showed marked reductions in mortality, infectious
      morbidity and length of stay. Recent studies no longer show beneficial effects
      and in contrast even demonstrated increased mortality. This opiniating review
      focuses on the latest information and the consequences for the use of glutamine
      and antioxidants in critically ill patients. RECENT FINDINGS: Positive effects in
      systematic reviews and meta-analyses are based on results from older, smaller and
      mainly single-centre studies. New information has challenged the conditional
      deficiency hypothesis concerning glutamine in critically ill patients. The recent
      REDOXS and MetaPlus trials studying the effects of glutamine, selenium and other
      antioxidants have shown no benefits and increased mortality. SUMMARY: Given that
      the first dictum in medicine is to do no harm, we cannot be confident that immune
      modulating nutrient supplementation with glutamine and antioxidants is effective
      and well tolerated for critically ill patients. Until more data are available, it
      is probably better not to routinely administer glutamine and antioxidants in
      nonphysiological doses to mechanically ventilated critically ill patients.

PMID- 25590614
TI  - The Epstein-Barr virus encoded BART miRNAs potentiate tumor growth in vivo.
AB  - The human herpes virus Epstein-Barr virus (EBV) latently infects and drives the
      proliferation of B lymphocytes in vitro and is associated with several forms of
      lymphoma and carcinoma in vivo. The virus encodes ~30 miRNAs in the BART region,
      the function of most of which remains elusive. Here we have used a new mouse
      xenograft model of EBV driven carcinomagenesis to demonstrate that the BART
      miRNAs potentiate tumor growth and development in vivo. No effect was seen on
      invasion or metastasis, and the growth promoting activity was not seen in vitro.
      In vivo tumor growth was not associated with the expression of specific BART
      miRNAs but with up regulation of all the BART miRNAs, consistent with previous
      observations that all the BART miRNAs are highly expressed in all of the EBV
      associated cancers. Based on these observations, we suggest that deregulated
      expression of the BART miRNAs potentiates tumor growth and represents a general
      mechanism behind EBV associated oncogenesis. 

PMID- 25590615
TI  - Small indels induced by CRISPR/Cas9 in the 5' region of microRNA lead to its
      depletion and Drosha processing retardance.
AB  - MicroRNA knockout by genome editing technologies is promising. In order to extend
      the application of the technology and to investigate the function of a specific
      miRNA, we used CRISPR/Cas9 to deplete human miR-93 from a cluster by targeting
      its 5' region in HeLa cells. Various small indels were induced in the targeted
      region containing the Drosha processing site and seed sequences. Interestingly,
      we found that even a single nucleotide deletion led to complete knockout of the
      target miRNA with high specificity. Functional knockout was confirmed by
      phenotype analysis. Furthermore, de novo microRNAs were not found by RNA-seq.
      Nevertheless, expression of the pri-microRNAs was increased. When combined with
      structural analysis, the data indicated that biogenesis was impaired. Altogether,
      we showed that small indels in the 5' region of a microRNA result in sequence
      depletion as well as Drosha processing retard. 

PMID- 25590617
TI  - Hydrolysis of ketene catalyzed by formic acid: modification of reaction
      mechanism, energetics, and kinetics with organic acid catalysis.
AB  - The hydrolysis of ketene (H2C?C?O) to form acetic acid involving two water
      molecules and also separately in the presence of one to two water molecules and
      formic acid (FA) was investigated. Our results show that, while the currently
      accepted indirect mechanism, involving addition of water across the carbonyl C?O
      bond of ketene to form an ene-diol followed by tautomerization of the ene-diol to
      form acetic acid, is the preferred pathway when water alone is present, with
      formic acid as catalyst, addition of water across the ketene C?C double bond to
      directly produce acetic acid becomes the kinetically favored pathway for
      temperatures below 400 K. We find not only that the overall barrier for ketene
      hydrolysis involving one water molecule and formic acid (H2C2O + H2O + FA) is
      significantly lower than that involving two water molecules (H2C2O + 2H2O) but
      also that FA is able to reduce the barrier height for the direct path, involving
      addition of water across the C?C double bond, so that it is essentially identical
      with (6.4 kcal/mol) that for the indirect ene-diol formation path involving
      addition of water across the C?O bond. For the case of ketene hydrolysis
      involving two water molecules and formic acid (H2C2O + 2H2O + FA), the barrier
      for the direct addition of water across the C?C double bond is reduced even
      further and is 2.5 kcal/mol lower relative to the ene-diol path involving
      addition of water across the C?O bond. In fact, the hydrolysis barrier for the
      H2C2O + 2H2O + FA reaction through the direct path is sufficiently low (2.5
      kcal/mol) for it to be an energetically accessible pathway for acetic acid
      formation under atmospheric conditions. Given the structural similarity between
      acetic and formic acid, our results also have potential implications for aqueous
      phase chemistry. Thus, in an aqueous environment, even in the absence of formic
      acid, though the initial mechanism for ketene hydrolysis is expected to involve
      addition of water across the carbonyl bond as is currently accepted, the
      production and accumulation of acetic acid will likely alter the preferred
      pathway to one involving addition of water across the ketene C?C double bond as
      the reaction proceeds. 

PMID- 25590619
TI  - BMI as a mediator of the relationship between muscular fitness and
      cardiometabolic risk in children: a mediation analysis.
AB  - OBJECTIVE: Muscular fitness levels have been associated with cardiometabolic risk
      in children, although whether body weight acts as a confounder or as an
      intermediate variable in this relationship remains controversial. The aim of this
      study was to examine whether the association between muscular fitness and
      cardiometabolic risk factors is mediated by body mass index (BMI). DESIGN AND
      METHODS: Cross-sectional study using a sample of 1158 schoolchildren aged 8-11
      years from the province of Cuenca, Spain. We measured anthropometrics and
      biochemical variables and we calculated a muscular fitness index as the sum of z
      scores of handgrip dynamometry/weight and standing long jump, and we estimated a
      previously validated cardiometabolic risk index (CMRI). Linear regression models
      were fitted for mediation analysis to assess whether the association between
      muscular fitness and cardiometabolic risk was mediated by BMI. RESULTS: Children
      with normal weight (NW) had a better cardiometabolic risk profile than their
      overweight (OW) or obese (OB) peers after controlling for muscular fitness.
      Marginal estimated mean +/- SE values for NW, OW and OB categories of CMRI were 
      0.75 +/- 0.06 < 0.84 +/- 0.10 < 2.18 +/- 0.16 in boys and -0.73 +/- 0.06 < 0.96
      +/- 0.10 < 2.71 +/- 0.17 in girls, both p < 0.001. Children with higher levels of
      muscular fitness had a better cardiometabolic risk profile (CMRI marginal
      estimated mean +/- SE 1.04 +/- 0.13 > 0.05 +/- 0.09 >-1.16 +/- 0.13 for lower,
      middle and upper quartiles of muscular fitness in boys and 1.01 +/- 0.16 > 0.10
      +/- 0.09 > -1.02 +/- 0.15 in girls, both p < 0.001), but differences disappeared
      when controlling for BMI. BMI acted as a full mediator between muscular fitness
      and most cardiometabolic risk factors (Sobel test z = -11.44 for boys; z = -11.83
      for girls; p < 0.001 in CMRI mediation model) and as a partial mediator in the
      case of waist circumference (Sobel test z=-14.86 for boys; z=-14.51 for girls;
      p<0.001). CONCLUSIONS: BMI mediates the association between muscular fitness and
      cardiometabolic risk in schoolchildren. Overall, good muscular fitness is
      associated with lower cardiometabolic risk, but particularly when accompanied by
      normal weight.

PMID- 25590620
TI  - Acoustic and temporal partitioning of cicada assemblages in city and mountain
      environments.
AB  - Comparing adaptations to noisy city environments with those to natural mountain
      environments on the community level can provide significant insights that allow
      an understanding of the impact of anthropogenic noise on invertebrates that
      employ loud calling songs for mate attraction, especially when each species has
      its distinct song, as in the case of cicadas. In this study, we investigated the
      partitioning strategy of cicada assemblages in city and mountain environments by
      comparing the acoustic features and calling activity patterns of each species,
      recorded using automated digital recording systems. Our comparison of activity
      patterns of seasonal and diel calling revealed that there was no significant
      temporal partitioning of cicada assemblages in either environment. In addition,
      there was no correlation between the acoustic distance based on spectral features
      and temporal segregation. Heterospecific spectral overlap was low in both city
      and mountain environments, although city and mountain cicada assemblages were
      subject to significantly different levels of anthropogenic or interspecific
      noise. Furthermore, for the common species found in both environments, the
      calling activity patterns at both seasonal and diel time scales were
      significantly consistent across sites and across environments. We suggest that
      the temporal calling activity is constrained by endogenous factors for each
      species and is less flexible in response to external factors, such as
      anthropogenic noise. As a result, cicada assemblages in city environments with
      low species diversity do not demonstrate a more significant temporal partitioning
      than those in mountain environments with high species diversity. 

PMID- 25590621
TI  - DNA is an antimicrobial component of neutrophil extracellular traps.
AB  - Neutrophil extracellular traps (NETs) comprise an ejected lattice of chromatin
      enmeshed with granular and nuclear proteins that are capable of capturing and
      killing microbial invaders. Although widely employed to combat infection, the
      antimicrobial mechanism of NETs remains enigmatic. Efforts to elucidate the
      bactericidal component of NETs have focused on the role of NET-bound proteins
      including histones, calprotectin and cathepsin G protease; however, exogenous and
      microbial derived deoxyribonuclease (DNase) remains the most potent inhibitor of
      NET function. DNA possesses a rapid bactericidal activity due to its ability to
      sequester surface bound cations, disrupt membrane integrity and lyse bacterial
      cells. Here we demonstrate that direct contact and the phosphodiester backbone
      are required for the cation chelating, antimicrobial property of DNA. By treating
      NETs with excess cations or phosphatase enzyme, the antimicrobial activity of
      NETs is neutralized, but NET structure, including the localization and function
      of NET-bound proteins, is maintained. Using intravital microscopy, we visualized
      NET-like structures in the skin of a mouse during infection with Pseudomonas
      aeruginosa. Relative to other bacteria, P. aeruginosa is a weak inducer of
      NETosis and is more resistant to NETs. During NET exposure, we demonstrate that
      P. aeruginosa responds by inducing the expression of surface modifications to
      defend against DNA-induced membrane destabilization and NET-mediated killing.
      Further, we show induction of this bacterial response to NETs is largely due to
      the bacterial detection of DNA. Therefore, we conclude that the DNA backbone
      contributes both to the antibacterial nature of NETs and as a signal perceived by
      microbes to elicit host-resistance strategies. 

PMID- 25590618
TI  - Deep sequencing of the murine olfactory receptor neuron transcriptome.
AB  - The ability of animals to sense and differentiate among thousands of odorants
      relies on a large set of olfactory receptors (OR) and a multitude of accessory
      proteins within the olfactory epithelium (OE). ORs and related signaling
      mechanisms have been the subject of intensive studies over the past years, but
      our knowledge regarding olfactory processing remains limited. The recent
      development of next generation sequencing (NGS) techniques encouraged us to
      assess the transcriptome of the murine OE. We analyzed RNA from OEs of female and
      male adult mice and from fluorescence-activated cell sorting (FACS)-sorted
      olfactory receptor neurons (ORNs) obtained from transgenic OMP-GFP mice. The
      Illumina RNA-Seq protocol was utilized to generate up to 86 million reads per
      transcriptome. In OE samples, nearly all OR and trace amine-associated receptor
      (TAAR) genes involved in the perception of volatile amines were detectably
      expressed. Other genes known to participate in olfactory signaling pathways were
      among the 200 genes with the highest expression levels in the OE. To identify OE
      specific genes, we compared olfactory neuron expression profiles with RNA-Seq
      transcriptome data from different murine tissues. By analyzing different
      transcript classes, we detected the expression of non-olfactory GPCRs in ORNs and
      established an expression ranking for GPCRs detected in the OE. We also
      identified other previously undescribed membrane proteins as potential new
      players in olfaction. The quantitative and comprehensive transcriptome data
      provide a virtually complete catalogue of genes expressed in the OE and present a
      useful tool to uncover candidate genes involved in, for example, olfactory
      signaling, OR trafficking and recycling, and proliferation. 

PMID- 25590622
TI  - Interaction between Helicobacter pylori and latent toxoplasmosis and demographic
      variables on cognitive function in young to middle-aged adults.
AB  - Helicobacter pylori and latent toxoplasmosis are widespread diseases that have
      been associated with cognitive deficits and Alzheimer's disease. We sought to
      determine whether interactions between Helicobacter pylori and latent
      toxoplasmosis, age, race-ethnicity, educational attainment, economic status, and
      general health predict cognitive function in young and middle-aged adults. To do
      so, we used multivariable regression and multivariate models to analyze data
      obtained from the United States' National Health and Nutrition Examination Survey
      from the Centers for Disease Control and Prevention, which can be weighted to
      represent the US population. In this sample, we found that 31.6 percent of women
      and 36.2 percent of men of the overall sample had IgG Antibodies against
      Helicobacter pylori, although the seroprevalence of Helicobacter pylori varied
      with sociodemographic variables. There were no main effects for Helicobacter
      pylori or latent toxoplasmosis for any of the cognitive measures in models
      adjusting for age, sex, race-ethnicity, educational attainment, economic
      standing, and self-rated health predicting cognitive function. However,
      interactions between Helicobacter pylori and race-ethnicity, educational
      attainment, latent toxoplasmosis in the fully adjusted models predicted cognitive
      function. People seropositive for both Helicobacter pylori and latent
      toxoplasmosis - both of which appear to be common in the general population -
      appear to be more susceptible to cognitive deficits than are people seropositive
      for either Helicobacter pylori and or latent toxoplasmosis alone, suggesting a
      synergistic effect between these two infectious diseases on cognition in young to
      middle-aged adults. 

PMID- 25590623
TI  - Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin
      and cisplatin-based treatment of testicular cancer patients and relate to
      endothelial damage.
AB  - INTRODUCTION: Chemotherapy-related endothelial damage contributes to the early
      development of cardiovascular morbidity in testicular cancer patients. We aimed
      to identify relevant mechanisms of and search for candidate biomarkers for this
      endothelial damage. METHODS: Human micro-vascular endothelial cells (HMEC-1) were
      exposed to bleomycin or cisplatin with untreated samples as control. 18k cDNA
      microarrays were used. Gene expression differences were analysed at single gene
      level and in gene sets clustered in biological pathways and validated by qRT-PCR.
      Protein levels of a candidate biomarker were measured in testicular cancer
      patient plasma before, during and after bleomycin-etoposide-cisplatin
      chemotherapy, and related to endothelial damage biomarkers (von Willebrand Factor
      (vWF), high-sensitivity C-Reactive Protein (hsCRP)). RESULTS: Microarray data
      identified several genes with highly differential expression; e.g. Growth
      Differentiation Factor 15 (GDF-15), Activating Transcription Factor 3 (ATF3) and
      Amphiregulin (AREG). Pathway analysis revealed strong associations with 'p53' and
      'Diabetes Mellitus' gene sets. Based on known function, we measured GDF-15
      protein levels in 41 testicular patients during clinical follow-up. Pre
      chemotherapy GDF-15 levels equalled controls. Throughout chemotherapy GDF-15, vWF
      and hsCRP levels increased, and were correlated at different time-points.
      CONCLUSION: An unbiased approach in a preclinical model revealed genes related to
      chemotherapy-induced endothelial damage, like GDF-15. The increases in plasma GDF
      15 levels in testicular cancer patients during chemotherapy and its association
      with vWF and hsCRP suggest that GDF-15 is a potentially useful biomarker related
      to endothelial damage.

PMID- 25590624
TI  - Metabolism of androstenone, 17beta-estradiol and dihydrotestosterone in primary
      cultured pig hepatocytes and the role of 3beta-hydroxysteroid dehydrogenase in
      this process.
AB  - Steroids metabolism plays an important role in mammals and contributes to quality
      of pig meat. The main objective of this study was to identify metabolites of
      androstenone, 17beta-estradiol and dihydrotestosterone using primary cultured pig
      hepatocytes as a model system. The role of 3beta-hydroxysteroid dehydrogenase
      (3betaHSD) in regulation of steroid metabolism was also validated using
      trilostane, a specific 3betaHSD inhibitor. Steroid glucuronide conjugated
      metabolites were detected by liquid chromatography time of flight mass
      spectrometry (LC-TOF-MS). 3betaHSD enzyme was essential for metabolism of
      androstenone to 5alpha-androst-16-en-3beta-ol, which then formed androstenone
      glucuronide conjugate. Metabolism of 17beta-estradiol was accompanied by
      formation of glucuronide-conjugated estrone and glucuronide-conjugated estradiol.
      The ratio of the two metabolites was around 5:1. 3betaHSD enzyme was not involved
      in 17beta-estradiol metabolism. 5alpha-Dihydrotestosterone-17beta-glucuronide was
      identified as a dihydrotestosterone metabolite, and this metabolism was related
      to 3betaHSD enzyme activity as demonstrated by inhibition study.

PMID- 25590625
TI  - Emission of titanium dioxide nanoparticles from building materials to the
      environment by wear and weather.
AB  - In the present work, we investigate the effect of weathering duration on a
      commercial photocatalytic nanocoating on the basis of its nanoparticle emission
      tendency into two media, air and water. It is found that increased weathering
      duration results in stepwise structural deterioration of the nanocoating, which
      in turn decreases the nanocoating life, changes the nanocoating removal
      mechanism, and increases the particle emission concentration. Emission of free
      TiO2 nanoparticles is found to be weathering duration dependent. Three quantities
      are introduced: emission transition pace (ETP), stable emission level (SEL), and
      stable emission duration (SED). By linear extrapolation of these quantities from
      short weathering durations, complete failure of the nanocoatings can be predicted
      and, moreover, the potential increase of nanoparticles release into the air. 

PMID- 25590626
TI  - Male mosquitoes as vehicles for insecticide.
AB  - BACKGROUND: The auto-dissemination approach has been shown effective at treating
      cryptic refugia that remain unaffected by existing mosquito control methods. This
      approach relies on adult mosquito behavior to spread larvicide to breeding sites
      at levels that are lethal to immature mosquitoes. Prior studies demonstrate that
      'dissemination stations,' deployed in mosquito-infested areas, can contaminate
      adult mosquitoes, which subsequently deliver the larvicide to breeding sites. In
      some situations, however, preventative measures are needed, e.g., to mitigate
      seasonal population increases. Here we examine a novel approach that combines
      elements of autocidal and auto-dissemination strategies by releasing artificially
      reared, male mosquitoes that are contaminated with an insecticide. METHODOLOGY:
      Laboratory and field experiments examine for model-predicted impacts of
      pyriproxyfen (PPF) directly applied to adult male Aedes albopictus, including (1)
      the ability of PPF-treated males to cross-contaminate females and to (2) deliver
      PPF to breeding sites. PRINCIPAL FINDINGS: Similar survivorship was observed in
      comparisons of PPF-treated and untreated males. Males contaminated both female
      adults and oviposition containers in field cage tests, at levels that eliminated
      immature survivorship. Field trials demonstrate an ability of PPF-treated males
      to transmit lethal doses to introduced oviposition containers, both in the
      presence and absence of indigenous females. A decline in the Ae. albopictus
      population was observed following the introduction of PPF-treated males, which
      was not observed in two untreated field sites. CONCLUSIONS/SIGNIFICANCE: The
      results demonstrate that, in cage and open field trials, adult male Ae.
      albopictus can tolerate PPF and contaminate, either directly or indirectly, adult
      females and immature breeding sites. The results support additional development
      of the proposed approach, in which male mosquitoes act as vehicles for
      insecticide delivery, including exploration of the approach with additional
      medically important mosquito species. The novelty and importance of this approach
      is an ability to safely achieve auto-dissemination at levels of intensity that
      may not be possible with an auto-dissemination approach that is based on
      indigenous females. Specifically, artificially-reared males can be released and
      sustained at any density required, so that the potential for impact is limited
      only by the practical logistics of mosquito rearing and release, rather than
      natural population densities and the self-limiting impact of an intervention upon
      them.

PMID- 25590627
TI  - Baseline and strategic effects behind mindful emotion regulation: behavioral and
      physiological investigation.
AB  - One of the consequences of extensive mindfulness practice is a reduction of
      anxiety and depression, but also a capacity to regulate negative emotions. In
      this study, we explored four key questions concerning mindfulness training: (1)
      What are the processes by which mindfulness regulates our emotions? (2) Can
      mindfulness be applied to social emotions? (3) Does mindfulness training affect
      emotionally driven behavior towards others? (4) Does mindfulness alter
      physiological reactivity? To address these questions, we tested, in two
      experiments, the ability of mindfulness meditators to regulate interpersonal
      emotions (Experiment 1) and interactive behaviors (Experiment 2) as compared to
      naive controls. To better understand the mechanisms by which mindfulness
      regulates emotions, we asked participants to apply two strategies: a cognitive
      strategy (mentalizing, a form of reappraisal focused on the intentions of others)
      and an experiential strategy derived from mindfulness principles (mindful
      detachment). Both groups were able to regulate interpersonal emotions by means of
      cognitive (mentalizing) and experiential (mindful detachment) strategies. In
      Experiment 1, a simple effect of meditation, independent from the implementation
      of the strategies, resulted in reduced emotional and physiological reactivity, as
      well as in increased pleasantness for meditators when compared to controls,
      providing evidence of baseline regulation. In Experiment 2, one visible effect of
      the strategy was that meditators outperformed controls in the experiential
      (mindful detachment) but not in the cognitive (mentalize) strategy, showing
      stronger modulation of their interactive behavior (less punishments) and
      providing evidence of a strategic behavioral regulation. Based on these results,
      we suggest that mindfulness can influence interpersonal emotional reactions
      through an experiential mechanism, both at a baseline level and a strategic
      level, thereby altering the subjective and physiological perception of emotions,
      but also biasing interactive social behavior. 

PMID- 25590628
TI  - Reprogramming of Yersinia from virulent to persistent mode revealed by complex in
      vivo RNA-seq analysis.
AB  - We recently found that Yersinia pseudotuberculosis can be used as a model of
      persistent bacterial infections. We performed in vivo RNA-seq of bacteria in
      small cecal tissue biopsies at early and persistent stages of infection to
      determine strategies associated with persistence. Comprehensive analysis of mixed
      RNA populations from infected tissues revealed that Y. pseudotuberculosis
      undergoes transcriptional reprogramming with drastic down-regulation of T3SS
      virulence genes during persistence when the pathogen resides within the cecum. At
      the persistent stage, the expression pattern in many respects resembles the
      pattern seen in vitro at 26oC, with for example, up-regulation of flagellar genes
      and invA. These findings are expected to have impact on future rationales to
      identify suitable bacterial targets for new antibiotics. Other genes that are up
      regulated during persistence are genes involved in anaerobiosis, chemotaxis, and
      protection against oxidative and acidic stress, which indicates the influence of
      different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades
      influence the pattern of bacterial gene expression during persistence.
      Furthermore, arcA, fnr, frdA, and wrbA play critical roles in persistence. Our
      findings suggest a model for the life cycle of this enteropathogen with
      reprogramming from a virulent to an adapted phenotype capable of persisting and
      spreading by fecal shedding. 

PMID- 25590629
TI  - A hormone-responsive C1-domain-containing protein At5g17960 mediates stress
      response in Arabidopsis thaliana.
AB  - Phytohormones play a critical role in mediating plant stress response. They
      employ a variety of proteins for coordinating such processes. In Arabidopsis
      thaliana, some members of a Cys-rich protein family known as C1-clan proteins
      were involved in stress response, but the actual function of the protein family
      is largely unknown. We studied At5g17960, a C1-clan protein member that possesses
      three unique C1 signature domains viz. C1_2, C1_3 and ZZ/PHD type. Additionally,
      we identified 72 other proteins in A. thaliana that contain all three unique
      signature domains. Subsequently, the 73 proteins were phylogenetically classified
      into IX subgroups. Promoter motif analysis of the 73 genes identified the
      presence of hormone-responsive and stress-responsive putative cis-regulatory
      elements. Furthermore, we observed that transcript levels of At5g17960 were
      induced in response to different hormones and stress treatments. At1g35610 and
      At3g13760, two other members of subgroup IV, also showed upregulation upon GA3,
      biotic and abiotic stress treatments. Moreover, seedlings of independent
      transgenic A. thaliana lines ectopically expressing or suppressing At5g17960 also
      showed differential regulation of several abiotic stress-responsive marker genes.
      Thus, our data suggest that C1-domain-containing proteins have a role to play in
      plant hormone-mediated stress responses, thereby assigning a putative function
      for the C1-clan protein family.

PMID- 25590630
TI  - Positive effect of human milk feeding during NICU hospitalization on 24 month
      neurodevelopment of very low birth weight infants: an Italian cohort study.
AB  - The aim of this study was to determine the effect of human milk feeding during
      NICU hospitalization on neurodevelopment at 24 months of corrected age in very
      low birth weight infants. A cohort of 316 very low birth weight newborns (weight
      <= 1500 g) was prospectively enrolled in a follow-up program on admission to the
      Neonatal Intensive Care Unit of S. Orsola Hospital, Bologna, Italy, from January
      2005 to June 2011. Neurodevelopment was evaluated at 24 months corrected age
      using the Griffiths Mental Development Scale. The effect of human milk nutrition
      on neurodevelopment was first investigated using a multiple linear regression
      model, to adjust for the effects of gestational age, small for gestational age,
      complications at birth and during hospitalization, growth restriction at
      discharge and socio-economic status. Path analysis was then used to refine the
      multiple regression model, taking into account the relationships among predictors
      and their temporal sequence. Human milk feeding during NICU hospitalization and
      higher socio-economic status were associated with better neurodevelopment at 24
      months in both models. In the path analysis model intraventricular hemorrhage
      periventricular leukomalacia and growth restriction at discharge proved to be
      directly and independently associated with poorer neurodevelopment. Gestational
      age and growth restriction at birth had indirect significant effects on
      neurodevelopment, which were mediated by complications that occurred at birth and
      during hospitalization, growth restriction at discharge and type of feeding. In
      conclusion, our findings suggest that mother's human milk feeding during
      hospitalization can be encouraged because it may improve neurodevelopment at 24
      months corrected age. 

PMID- 25590631
TI  - Long-term exposure to traffic emissions and fine particulate matter and lung
      function decline in the Framingham heart study.
AB  - RATIONALE: Few studies have examined associations between long-term exposure to
      fine particulate matter (PM2.5) and lung function decline in adults. OBJECTIVES:
      To determine if exposure to traffic and PM2.5 is associated with longitudinal
      changes in lung function in a population-based cohort in the Northeastern United
      States, where pollution levels are relatively low. METHODS: FEV1 and FVC were
      measured up to two times between 1995 and 2011 among 6,339 participants of the
      Framingham Offspring or Third Generation studies. We tested associations between
      residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by
      a land-use model using satellite measurements of aerosol optical thickness) and
      lung function. We examined differences in average lung function using mixed
      effects models and differences in lung function decline using linear regression
      models. Current smokers were excluded. Models were adjusted for age, sex, height,
      weight, pack-years, socioeconomic status indicators, cohort, time, season, and
      weather. MEASUREMENTS AND MAIN RESULTS: Living less than 100 m from a major
      roadway was associated with a 23.2 ml (95% confidence interval [CI], -44.4 to 
      1.9) lower FEV1 and a 5.0 ml/yr (95% CI, -9.0 to -0.9) faster decline in FEV1
      compared with more than 400 m. Each 2 MUg/m(3) increase in average of PM2.5 was
      associated with a 13.5 ml (95% CI, -26.6 to -0.3) lower FEV1 and a 2.1 ml/yr (95%
      CI, -4.1 to -0.2) faster decline in FEV1. There were similar associations with
      FVC. Associations with FEV1/FVC ratio were weak or absent. CONCLUSIONS: Long-term
      exposure to traffic and PM2.5, at relatively low levels, was associated with
      lower FEV1 and FVC and an accelerated rate of lung function decline.

PMID- 25590634
TI  - Effect of running speed and leg prostheses on mediolateral foot placement and its
      variability.
AB  - This study examined the effects of speed and leg prostheses on mediolateral (ML)
      foot placement and its variability in sprinters with and without transtibial
      amputations. We hypothesized that ML foot placement variability would: 1.
      increase with running speed up to maximum speed and 2. be symmetrical between the
      legs of non-amputee sprinters but asymmetrically greater for the affected leg of
      sprinters with a unilateral transtibial amputation. We measured the midline of
      the body (kinematic data) and center of pressure (kinetic data) in the ML
      direction while 12 non-amputee sprinters and 7 Paralympic sprinters with
      transtibial amputations (6 unilateral, 1 bilateral) ran across a range of speeds
      up to maximum speed on a high-speed force measuring treadmill. We quantified ML
      foot placement relative to the body's midline and its variability. We interpret
      our results with respect to a hypothesized relation between ML foot placement
      variability and lateral balance. We infer that greater ML foot placement
      variability indicates greater challenges with maintaining lateral balance. In non
      amputee sprinters, ML foot placement variability for each leg increased
      substantially and symmetrically across speed. In sprinters with a unilateral
      amputation, ML foot placement variability for the affected and unaffected leg
      also increased substantially, but was asymmetric across speeds. In general, ML
      foot placement variability for sprinters with a unilateral amputation was within
      the range observed in non-amputee sprinters. For the sprinter with bilateral
      amputations, both affected legs exhibited the greatest increase in ML foot
      placement variability with speed. Overall, we find that maintaining lateral
      balance becomes increasingly challenging at faster speeds up to maximum speed but
      was equally challenging for sprinters with and without a unilateral transtibial
      amputation. Finally, when compared to all other sprinters in our subject pool,
      maintaining lateral balance appears to be the most challenging for the Paralympic
      sprinter with bilateral transtibial amputations. 

PMID- 25590632
TI  - Emerging role of RNA*DNA hybrids in C9orf72-linked neurodegeneration.
AB  - RNA plays an active role in structural polymorphism of the genome through the
      formation of stable RNA*DNA hybrids (R-loops). R-loops can modulate normal
      physiological processes and are also associated with pathological conditions,
      such as those related to nucleotide repeat expansions. A guanine-rich
      hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72)
      has been linked to a spectrum of neurological conditions including amyotrophic
      lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we discuss the
      possible roles, both locally and genome-wide, of R-loops that may arise from the
      C9orf72 hexanucleotide repeat. R-loops have the potential to influence the
      pathological processes identified in many repeat expansion diseases, such as
      repeat instability, transcriptional dysregulation, epigenetic modification, and
      antisense-mediated gene regulation. We propose that, given the wide-ranging
      consequences of R-loops in the cell, these structures could underlie multiple
      pathological processes in C9orf72-linked neurodegeneration. 

PMID- 25590633
TI  - Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA
      damage-response pathway in SCA3.
AB  - Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD),
      is an untreatable autosomal dominant neurodegenerative disease, and the most
      common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of
      a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region
      of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding
      expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo,
      and is deposited as aggregates in the SCA3 brain. A large body of literature
      suggests that the loss of function of the native ATNX3-interacting proteins that
      are deposited in the polyQ aggregates contributes to cellular toxicity, systemic
      neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a
      significant understanding of the disease etiology of SCA3, the molecular
      mechanism by which the polyQ expansions in the mutant ATXN3 induce
      neurodegeneration in SCA3 has remained elusive. In the present study, we show
      that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'
      phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting
      in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks,
      and subsequent chronic activation of the DNA damage-response ataxia
      telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent
      accumulation of DNA damage/strand breaks and chronic activation of the
      serine/threonine kinase ATM and the downstream p53 and protein kinase C-delta pro
      apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in
      SCA3. Either PNKP overexpression or pharmacological inhibition of ATM
      dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism
      by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling
      pathways provides a molecular basis for neurodegeneration due to PNKP
      inactivation in SCA3, and for the first time offers a possible approach to
      treatment. 

PMID- 25590635
TI  - Sequence analysis of the capsid gene during a genotype II.4 dominated norovirus
      season in one university hospital: identification of possible transmission
      routes.
AB  - Norovirus (NoV) is a leading cause of gastroenteritis and genotype II.4 (GII.4)
      is responsible for the majority of nosocomial NoV infections. Our objective was
      to examine whether sequencing of the capsid gene might be a useful tool for the
      hospital outbreak investigation to define possible transmission routes. All NoV
      positive samples submitted from one university hospital during the 2007/8 season
      were selected. Genotyping of selected samples by partial polymerase gene
      sequencing had shown that the majority belonged to the GII.4 variant Den Haag
      2006b and had identical polymerase sequences. Sequences of the capsid gene (1412
      nucleotides) were obtained from the first available sample from 55 patients. From
      six immunocompromised patients with persistent infections a second sample was
      also included. As a control for a point-source outbreak, five samples from a
      foodborne outbreak caused by the same GII.4 variant were analyzed. Forty-seven of
      the inpatients (85%) were infected with the GII.4 variant Den Haag 2006b.
      Phylogenetic analysis of the Den Haag 2006b sequences identified four distinct
      outbreaks in different departments and a fifth outbreak with possible inter
      department spread. In addition, a more heterogeneous cluster with evidence of
      repeated introductions from the community, but also possible inter-department
      spread was observed. In all six patients with paired sequences, evidence for in
      vivo evolution of the virus was found. Capsid gene sequencing showed substantial
      sequence variation among NoV GII.4 variant Den Haag 2006b strains from one single
      institution during a nine months' period. This method proved useful to understand
      the local epidemiology and, when used promptly, has the potential to make
      infection control measures more targeted. 

PMID- 25590636
TI  - Altered Ca2+ kinetics associated with alpha-actinin-3 deficiency may explain
      positive selection for ACTN3 null allele in human evolution.
AB  - Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein alpha
      actinin-3 due to homozygosity for a common null polymorphism (R577X) in the ACTN3
      gene. alpha-Actinin-3 deficiency is detrimental to sprint performance in elite
      athletes and beneficial to endurance activities. In the human genome, it is very
      difficult to find single-gene loss-of-function variants that bear signatures of
      positive selection, yet intriguingly, the ACTN3 null variant has undergone strong
      positive selection during recent evolution, appearing to provide a survival
      advantage where food resources are scarce and climate is cold. We have previously
      demonstrated that alpha-actinin-3 deficiency in the Actn3 KO mouse results in a
      shift in fast-twitch fibres towards oxidative metabolism, which would be more
      "energy efficient" in famine, and beneficial to endurance performance. Prolonged
      exposure to cold can also induce changes in skeletal muscle similar to those
      observed with endurance training, and changes in Ca2+ handling by the
      sarcoplasmic reticulum (SR) are a key factor underlying these adaptations. On
      this basis, we explored the effects of alpha-actinin-3 deficiency on Ca2+
      kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice,
      using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO
      mice showed: (i) an increased rate of decay of the twitch transient; (ii) a
      fourfold increase in the rate of SR Ca2+ leak; (iii) a threefold increase in the
      rate of SR Ca2+ pumping; and (iv) enhanced maintenance of tetanic Ca2+ during
      fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin
      and sarcalumenin, showed markedly increased expression in muscles of KO mice.
      Together, these changes in Ca2+ handling in the absence of alpha-actinin-3 are
      consistent with cold acclimatisation and thermogenesis, and offer an additional
      explanation for the positive selection of the ACTN3 577X null allele in
      populations living in cold environments during recent evolution. 

PMID- 25590638
TI  - Household costs of leprosy reactions (ENL) in rural India.
AB  - BACKGROUND: Erythema nodosum leprosum (ENL) is a common immune-mediated
      complication of lepromatous (LL) and borderline lepromatous (BL) leprosy. Most
      patients experience chronic or multiple acute ENL over many years during an
      economically active period of their lives. Understanding the economic burden of
      ENL is essential to provide effective patient support, yet this area has not been
      investigated. METHODS: Ninety-one patients with LL or BL leprosy attending a
      leprosy hospital in Purulia district of West Bengal, India, were interviewed
      using a structured questionnaire. Cases (n = 53) were identified as those who had
      one or more episodes of ENL within the last 3 years. Controls (n = 38) had LL or
      BL leprosy but no history of ENL. Data were collected on household income, direct
      and indirect costs, and coping strategies. FINDINGS: The total household cost was
      Rs 1543 per month or 27.9% (IQR 13.2-52.6) of monthly household income for cases,
      and Rs 237 per month or 4.9% (IQR 1.7-13.4) of monthly household income for
      controls. Indirect costs accounted for 65% of total household costs for cases.
      Direct costs accounted for the remaining 35% of household costs, and resulted
      almost entirely from treatment-seeking in the private sector. Total household
      costs exceeded 40% of household income for 37.7% of cases (n = 20) and 2.6% of
      controls (n = 1) [1 USD = 59 INR]. INTERPRETATION: Households affected by ENL
      face significant economic burden and are at risk of being pushed further into
      poverty. Health policy should acknowledge the importance of private sector
      provision and the significant contribution to total household costs of lost
      productivity (indirect cost). Further work is needed to explore this area and
      identify solutions.

PMID- 25590639
TI  - Combination therapy in the extended cardiovascular continuum: a focus on
      perindopril and amlodipine.
AB  - The progression of cardiovascular disease could be regarded as following
      atherosclerosis-related and age-related pathways. The starting points for these
      pathways are different--risk factors or aortic ageing--but they conclude in the
      same way: end-stage heart disease. Together these interlinked pathways form the
      extended cardiovascular continuum. Renin-angiotensin-aldosterone system (RAAS)
      inhibitors have been shown to interrupt or slow the progression of cardiovascular
      disease along one pathway, the cardiovascular atherosclerotic continuum.
      Cardiovascular protection with RAAS inhibitors varies; different RAAS inhibitors
      offer different levels of protection. Similarly, calcium channel blockers (CCBs)
      also have clearly shown protective effect of cardiovascular system, especially as
      it regards cerebrovascular disease risk. The AngloScandinavian Cardiac Outcomes
      Trial (ASCOT) showed that a combination of the angiotensin-converting enzyme
      (ACE) inhibitor perindopril and CCB amlodipine offered better cardiovascular
      protection in at-risk hypertensive patients than beta-blocker and thiazide. By
      attenuating the deleterious effects of cardiovascular disease at multiple stages
      of the extended cardiovascular continuum on top of lowering blood pressure (BP),
      perindopril and amlodipine could interrupt and slow the progression of
      cardiovascular disease. These antihypertensive agents have complementary vascular
      effects that enhance cardiovascular protection and reduce side-effects. Evidence
      from ASCOT shows that antihypertensive and vascular effects of amlodipine with
      and without perindopril have translated into real-life clinical benefits. A
      strategy using ACE inhibitors and CCBs, such as perindopril and amlodipine, to
      target multiple stages in both pathways of cardiovascular disease could
      effectively reduce cardiovascular risk and lower BP.

PMID- 25590640
TI  - Choroidal hyperreflective foci in Stargardt disease shown by spectral-domain
      optical coherence tomography imaging: correlation with disease severity.
AB  - IMPORTANCE: The presence of choroidal hyperreflective foci in Stargardt disease
      is, to our knowledge, a potentially new finding. Evaluation of these foci may aid
      in better understanding of the disease process. OBJECTIVES: To report the
      presence of choroidal hyperreflective foci in spectral-domain optical coherence
      tomography (SD-OCT) images from eyes with Stargardt disease and investigate the
      relationship between the number of hyperreflective foci and disease severity.
      DESIGN, SETTING, AND PARTICIPANTS: Twenty-six eyes of 13 patients with a clinical
      diagnosis of Stargardt disease were evaluated in a retrospective case series.
      Patient data were collected between January 1, 2009, and August 31, 2014. MAIN
      OUTCOMES AND MEASURES: The number of choroidal hyperreflective foci in Stargardt
      disease as well as correlation with visual acuity, central macular thickness
      (CMT), and disease duration were the main outcomes. A total of 707 macular SD-OCT
      scans of 13 patients with Stargardt disease were reviewed and evaluated for the
      presence and number of retinal/choroidal hyperreflective foci, central macular
      thickness, visual acuity, and disease duration. Enhanced depth imaging with OCT
      (EDI-OCT) scans available for 2 patients were compared with SD-OCT scans. A
      PubMed/Google search was performed to identify SD-OCT images in Stargardt
      disease; these findings were reviewed for the presence of choroidal
      hyperreflective foci. RESULTS: The mean (SD) numbers of hyperreflective foci in
      each retinal/choroidal layer in decreasing frequency were as follows: Bruch
      membrane/retinal pigment epithelial (RPE) complex, 78.22 (24.39);
      choriocapillaris, 25.77 (17.57); Sattler layer, 18.59 (12.89); outer retina,
      16.64 (6.96); inner retina, 0.95 (1.58); and Haller layer, 0.73 (0.87). The
      number of hyperreflective foci in the Bruch membrane/RPE complex increased
      exponentially with decreasing CMT (R2 = 0.99; P = .008). The number of
      hyperreflective foci in the Bruch membrane/RPE complex, choriocapillaris, and
      Sattler layer increased proportionally with decreasing visual acuity (R2 = 0.97,
      R2 = 0.95, and R2 = 0.99, respectively; and P = .007, P = .006, and P = .008,
      respectively). Direct correlation existed between the number of hyperreflective
      foci in the choriocapillaris and the Sattler layer and disease duration (R2 =
      0.98 and R2 = 0.99, respectively; and P = .006 and P =.009, respectively). In the
      10 studies on Stargardt disease, choroidal hyperreflective foci were present in
      51 of 54 SD-OCT images (94%). CONCLUSIONS AND RELEVANCE: Based on the findings of
      the present study, choroidal hyperreflective foci in Stargardt disease, prominent
      at the Bruch membrane/RPE complex, choriocapillaris, and Sattler layer, correlate
      with disease severity in terms of retinal atrophy, decline in vision, and disease
      duration. Further studies are necessary to assess whether these findings are
      unique to Stargardt disease.

PMID- 25590641
TI  - Antidiabetic and Renal Protective Properties of Berrycactus Fruit (Myrtillocactus
      geometrizans).
AB  - Native plants are exceedingly valuable because they are sources of natural
      products with applications for the treatment of various diseases. Berrycactus
      fruit (Myrtillocactus geometrizans) has been consumed in Mexico since ancient
      times due to its sweetness. The hypoglycemic and antioxidant effects of this
      fruit were evaluated in streptozotocin-induced diabetic rats by replacing the
      drinking water with berrycactus juice (2 or 4 g/kg). After 4 weeks of treatment,
      the diabetic animals showed an improvement in their conditions, as reflected by
      diminished circulating glucose levels (up to 50%), diminished triglycerides (up
      to 67%), and diminished total cholesterol (up to 35%) compared with diabetic
      nontreated controls, and these effects were dose dependent. The dose of 4 g/kg
      produced the best results. The administration of the juice improved renal
      function and helped to restore normal levels of glutathione and glutathione S
      transferase in the kidney. The expressions of two transcription factors that are
      relevant to normal functioning of the kidney changed due to the administration of
      the juice; compared to the diabetic nontreated controls, the level of nuclear
      factor kappa of B-cells diminished, and the total level of peroxisome
      proliferator-activated receptor gamma increased. The results of this study
      highlight the importance of the compounds that are present in berrycactus fruit
      as adjuvants in the treatment of diabetes and its renal complications.

PMID- 25590643
TI  - Fe(II)(pap-5NO2)2 and Fe(II)(qsal-5NO2)2 Schiff-base spin-crossover complexes: a
      rare example with photomagnetism and room-temperature bistability.
AB  - We focus here on the properties of Fe complexes formed with Schiff bases involved
      in the chemistry of Fe(III) spin-transition archetypes. The neutral Fe(pap-5NO2)2
      (1) and Fe(qsal-5NO2)2.Solv (2 and 2.Solv) compounds (Solv = 2H2O) derive from
      the reaction of Fe(II) salts with the condensation products of pyridine-2
      carbaldehyde with 2-hydroxy-5-nitroaniline (Hpap-5NO2) or 5-nitrosalicylaldehyde
      with quinolin-8-amine (Hqsal-5NO2), respectively. While the Fe(qsal-5NO2)2.Solv
      solid is essentially low spin (S = 0) and requires temperatures above 300 K to
      undergo a S = 0 <-> S = 2 spin-state switching, the Fe(pap-5NO2)2 one presents a
      strongly cooperative first-order transition (T? = 291 K, T? = 308 K) centered at
      room temperature associated with a photomagnetic effect at 10 K (TLIESST = 58 K).
      The investigation of these magnetic behaviors was conducted with single-crystal X
      ray diffraction (1, 100 and 320 K; 2, 100 K), Mossbauer, IR, UV-vis (1 and
      2.Solv), and differential scanning calorimetry (1) measurements. The Mossbauer
      analysis supports a description of these compounds as Fe(II) Schiff-base
      complexes and the occurrence of a metal-centered spin crossover process. In
      comparison with Fe(III) analogues, it appears that an expanded coordination
      sphere stabilizes the valence 2+ state of the Fe ion in both complexes. Strong
      hydrogen-bonding interactions that implicate the phenolato group bound to Fe(II)
      promote the required extra-stabilization of the S = 2 state and thus determines
      the spin transition of 1 centered at room temperature. In the lattice, the
      hydrogen-bonded sites form infinite chains interconnected via a three-dimensional
      network of intermolecular van der Waals contacts and pi-pi interactions.
      Therefore, the spin transition of 1 involves the synergetic influence of
      electrostatic and elastic interactions, which cause the enhancement of
      cooperativity and result in the bistability at room temperature. 

PMID- 25590642
TI  - Rapid Pore Cranial Drilling With External Ventricular Drainage for Treatment of
      Intraventricular Hemorrhage: A 36-Year Case Series.
AB  - This study aimed to describe the technique details of rapid pore cranial drilling
      with external ventricular drainage and document its clinical outcomes by
      highlighting the advantages over the traditional and modified cranial drilling
      technique. Intraventricular hemorrhage is one of the most severe subtypes of
      hemorrhagic stroke with high mortality. The amount of blood in the ventricles is
      associated with severity of outcomes, and fast removal of the blood clot is the
      key to a good prognosis. Between 1977 and 2013, 3773 patients admitted for
      intraventricular hemorrhage underwent rapid pore cranial drilling drainage. The
      therapeutic effects and clinical outcomes were retrospectively analyzed. Of these
      patients, 1049 (27.8%) experienced complete remission, 1788 (47.4%) had improved
      condition, and 936 (24.8%) died. A total of 3229 (85.6%) patients gained
      immediate remission. One typical case was illustrated to demonstrate the efficacy
      of the rapid pore drilling technique. Rapid pore cranial drilling drainage in
      patients with intraventricular hemorrhage is fast, effective, and provides
      immediate relief in patients with severe conditions. It could be a better
      alternative to the conventional drilling approach for treatment of
      intraventricular hemorrhage. A randomized controlled trial for direct comparison
      between the rapid pore cranial drilling drainage and conventional drilling
      technique is in urgent need. 

PMID- 25590645
TI  - Do patients' illness beliefs predict depression measures at six months in primary
      care; a longitudinal study.
AB  - BACKGROUND: Depressive disorders are prevalent and costly but there is a lack of
      evidence on how best to select treatments for mild to moderate depression in
      primary care. Illness beliefs have been shown to affect the outcome from physical
      illness, but there is limited information on the beliefs of patients who are
      depressed. AIMS: To measure patients' beliefs about depression at baseline and
      determine whether these relate to depression severity at six months. METHODS:
      Primary care patients with a recently diagnosed episode of depression completed
      the Beliefs about Depression Questionnaire and depression severity scores at
      baseline. The primary outcome was the change in depression severity score on the
      Hospital Anxiety and Depression Scale after six months. RESULTS: 227/292 (78%)
      participants completed follow-up questionnaires. Initial severity of depression
      at baseline, and particular beliefs about the causes, consequences and timeline
      of depression predicted poorer outcomes, whereas a belief in using exercise or
      keeping busy to treat depression predicted improved outcomes. Prescription of
      antidepressants did not appear to mediate these relationships. LIMITATIONS: This
      was an initial study using a new validated questionnaire and it cannot be
      predicted whether these results are representative or would be reproduced in
      other populations. Although participants were primary care patients whose GP
      (General Practitioner) had coded as having a new incident episode of depression
      in the preceding six months, 43% of participants stated they had been depressed
      for more than a year. Sufficient participants were recruited to ensure the study
      was adequately powered but participation rate was 30%, raising the possibility of
      response bias. CONCLUSIONS AND CLINICAL RELEVANCE: Illness beliefs may help to
      predict outcomes in depression and therefore assessing and addressing patients'
      beliefs about their depression may enhance treatment.

PMID- 25590644
TI  - DExD-box RNA-helicases in Listeria monocytogenes are important for growth,
      ribosomal maturation, rRNA processing and virulence factor expression.
AB  - RNA-helicases are proteins required for the unwinding of occluding secondary RNA
      structures, especially at low temperatures. In this work, we have deleted all 4
      DExD-box RNA helicases in various combinations in the Gram-positive pathogen
      Listeria monocytogenes. Our results show that 3 out of 4 RNA-helicases were
      important for growth at low temperatures, whereas the effect was less prominent
      at 37 degrees C. Over-expression of one RNA-helicase, Lmo1450, was able to
      overcome the reduced growth of the quadruple mutant strain at temperatures above
      26 degrees C, but not at lower temperatures. The maturation of ribosomes was
      affected in different degrees in the various strains at 20 degrees C, whereas the
      effect was marginal at 37 degrees C. This was accompanied by an increased level
      of immature 23S rRNA precursors in some of the RNA-helicase mutants at low
      temperatures. Although the expression of the PrfA regulated virulence factors
      ActA and LLO decreased in the quadruple mutant strain, this strain showed a
      slightly increased infection ability. Interestingly, even though the level of the
      virulence factor LLO was decreased in the quadruple mutant strain as compared
      with the wild-type strain, the hly-transcript (encoding LLO) was increased.
      Hence, our results could suggest a role for the RNA-helicases during translation.
      In this work, we show that DExD-box RNA-helicases are involved in bacterial
      virulence gene-expression and infection of eukaryotic cells. 

PMID- 25590647
TI  - Post trauma abdominal cocoon.
AB  - Abdominal cocoon or sclerosing peritonitis refers to a rare cause of intestinal
      obstruction due to formation of a membrane encasing the bowel. We report a case
      of abdominal cocoon post blunt trauma abdomen. The patient presented with a
      history of subacute intestinal obstruction and a mobile abdomen lump. Abdominal
      cocoon was diagnosed on computed tomography. He underwent adhesiolysis with
      excision of membrane. 

PMID- 25590646
TI  - Th17 down-regulation is involved in reduced progression of schistosomiasis
      fibrosis in ICOSL KO mice.
AB  - BACKGROUND: Granulomatous and fibrosing inflammation in response to parasite eggs
      is the main pathology that occurs during infection with Schistosoma spp. CD4+ T
      cells play critical roles in both host immune responses against parasitic
      infection and immunopathology in schistosomiasis,and coordinate many types of
      immune cells that contribute to fibrosis. ICOSL plays an important role in
      controlling specific aspects of T cell activation, differentiation, and function.
      Previous work has suggested that ICOS is essential for Th17 cell development.
      However, the immunopathogenesis of this pathway in schistosomiasis fibrosisis
      still unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using models of schistosomiasis in
      ICOSL KO and the C57BL/6 WT mice, we studied the role of the ICOSL/ICOS
      interaction in the mediation of the Th17 response in host granulomatous
      inflammation, particularly in liver fibrosis during S. japonicum infection, and
      investigated the immune responses and pathology of ICOSL KO mice in these models.
      The results showed that ICOSL KO mice exhibited improved survival, reduced liver
      granulomatous inflammation around parasite eggs, markedly inhibited hepatic
      fibrosis development, lower levels of Th17-related cytokines (IL-17/IL-21), Th2
      related cytokines (IL-4/IL-6/IL-10), a pro-fibrotic cytokine (IL-13), and TGF
      beta1, but higher level of Th1-related cytokine (IFN-gamma) compared to wild-type
      (WT) mice. The reduced progression of fibrogenesis was correlated with the down
      regulation of Th17 and Th2 and the elimination of ICOSL/ICOS interactions.
      CONCLUSIONS/SIGNIFICANCE: Our findings suggest that IL-17-producing cells
      contribute to the hepatic granulomatous inflammation and subsequent fibrosis.
      Importantly, there was a clearly positive correlation between the presence of IL
      17-producing cells and ICOS expression in ICOSL KO mice, and additional results
      indicated that Th17 was involved in the pathological tissue remodeling in liver
      fibrosis induced by schistosomiasis.

PMID- 25590648
TI  - Colovaginal anastomosis: A totally unacceptable surgical error.
AB  - INTRODUCTION: The low anterior rectal resection and double stapling technique are
      well-established surgical procedures with well-known pitfalls, potential
      complications, and preventive measures. Colovaginal anastomosis is a surgical
      error which should not occur. PRESENTATION OF CASE: A 39-year old woman underwent
      low anterior resection with double stapling technique, for rectal carcinoma in
      the City Hospital. On the fifth postoperative day she noticed passage of gas and
      two days later passage of feces from vagina. The surgeons who performed the
      operation explained to her that it is a normal condition for such modern
      procedure that is supervised by international educator engaged by the Government.
      The patient lived with this condition, passage of gas and feces from the vagina
      and nothing from anus for three months when her oncologist referred her for a
      second opinion at the University Clinic for Digestive Surgery. The digital
      examinations revealed a blind rectal stump, and feces in vagina; thus having the
      patient's history in mind, we assumed that the patient had a colovaginal
      anastomosis. Our assumption was confirmed by two succeeding radiological
      examinations. Initially, water soluble contrast enema was performed to assess the
      colon, when a clear-cut blind rectal stump was detected. Afterwards, the
      vaginography revealed a copious flow of contrast material from the vagina toward
      the sigmoid colon. After a few days, a restorative surgery was done. DISCUSSION:
      Most of the early postoperative complications are a result of surgical errors.
      CONCLUSION: We believe that there is no excuse for such a surgical error and
      postoperative follow-up.

PMID- 25590649
TI  - ZO-oming on growth control by junctional proteins.

PMID- 25590652
TI  - Cell proliferation-inducing protein 52/mitofilin is a surface antigen on
      undifferentiated human dental pulp stem cells.
AB  - Dental pulp is a soft tissue located inside the hard part of a tooth and it
      contains a stem cell population that can regenerate damaged dentin and/or pulp
      itself. Human dental pulp stem cells (hDPSCs) are multipotent adult stem cells
      that have the potential to be differentiated into a variety of cell types.
      Although cells cultured primarily from pulp tissue show heterogeneous phenotypes
      and variable efficiency in their dentinogenic differentiation, proper selection
      markers, which are specific to hDPSCs, are essential for the osteo/dentinogenic
      study of human dental pulp cells. We had previously screened a set of
      undifferentiation-specific cell surface antibodies of hDPSCs through decoy
      immunization. In this study, we show that one of these surface monoclonal
      antibodies, 3C4, is bound to intact pulp cells in a highly undifferentiation
      specific manner. The surface antigen protein bound specifically to 3C4 antibody
      was identified through direct immunoprecipitation and liquid chromatography
      tandem mass spectrometry as the cell proliferation-inducing protein 52/Mitofilin,
      which is a protein of the inner mitochondrial membrane and is a possible
      antagonist to maintaining mitochondrial activation during differentiation. The
      expression of mitofilin/3C4 antigen dramatically decreased during
      differentiation, and the depletion of mitofilin/3C4 antigen induced the
      expression of osteogenic/dentinogenic markers earlier than during normal
      differentiation. The 3C4-positive cells isolated by a magnetic-activated cell
      sorting system were differentiated with a higher efficiency than 3C4-negative
      cells. These results indicate that finding mitochondria-related stem cell markers
      is valuable to be able to identify and isolate primitive stem cells. 

PMID- 25590650
TI  - Reliable cell cycle commitment in budding yeast is ensured by signal integration.
AB  - Cell fate decisions are critical for life, yet little is known about how their
      reliability is achieved when signals are noisy and fluctuating with time. In this
      study, we show that in budding yeast, the decision of cell cycle commitment
      (Start) is determined by the time integration of its triggering signal Cln3. We
      further identify the Start repressor, Whi5, as the integrator. The instantaneous
      kinase activity of Cln3-Cdk1 is recorded over time on the phosphorylated Whi5,
      and the decision is made only when phosphorylated Whi5 reaches a threshold. Cells
      adjust the threshold by modulating Whi5 concentration in different nutrient
      conditions to coordinate growth and division. Our work shows that the strategy of
      signal integration, which was previously found in decision-making behaviors of
      animals, is adopted at the cellular level to reduce noise and minimize
      uncertainty. 

PMID- 25590651
TI  - The topography of frequency and time representation in primate auditory cortices.
AB  - Natural sounds can be characterised by their spectral content and temporal
      modulation, but how the brain is organized to analyse these two critical sound
      dimensions remains uncertain. Using functional magnetic resonance imaging, we
      demonstrate a topographical representation of amplitude modulation rate in the
      auditory cortex of awake macaques. The representation of this temporal dimension
      is organized in approximately concentric bands of equal rates across the superior
      temporal plane in both hemispheres, progressing from high rates in the posterior
      core to low rates in the anterior core and lateral belt cortex. In A1 the
      resulting gradient of modulation rate runs approximately perpendicular to the
      axis of the tonotopic gradient, suggesting an orthogonal organisation of spectral
      and temporal sound dimensions. In auditory belt areas this relationship is more
      complex. The data suggest a continuous representation of modulation rate across
      several physiological areas, in contradistinction to a separate representation of
      frequency within each area. 

PMID- 25590653
TI  - Investigators of studies of n = 1: pioneers or kamikazes?

PMID- 25590654
TI  - Catalytic metal ions and enzymatic processing of DNA and RNA.
AB  - CONSPECTUS: Two-metal-ion-dependent nucleases cleave the phosphodiester bonds of
      nucleic acids via the two-metal-ion (2M) mechanism. Several high-resolution X-ray
      structures portraying the two-metal-aided catalytic site, together with
      mutagenesis and kinetics studies, have demonstrated a functional role of the ions
      for catalysis in numerous metallonucleases. Overall, the experimental data
      confirm the general mechanistic hypothesis for 2M-aided phosphoryl transfer
      originally reported by Steitz and Steitz ( Proc. Natl. Acad. Sci. U.S.A. 1993 ,
      90 ( 14 ), 6498 - 6502 ). This seminal paper proposed that one metal ion favors
      the formation of the nucleophile, while the nearby second metal ion facilitates
      leaving group departure during RNA hydrolysis. Both metals were suggested to
      stabilize the enzymatic transition state. Nevertheless, static X-ray structures
      alone cannot exhaustively unravel how the two ions execute their functional role
      along the enzymatic reaction during processing of DNA or RNA strands when moving
      from reactants to products, passing through metastable intermediates and high
      energy transition states. In this Account, we discuss the role of multiscale
      molecular simulations in further disclosing mechanistic insights of 2M-aided
      catalysis for two prototypical enzymatic targets for drug discovery, namely,
      ribonuclease H (RNase H) and type II topoisomerase (topoII). In both examples,
      first-principles molecular simulations, integrated with structural data,
      emphasize a cooperative motion of the bimetal motif during catalysis. The
      coordinated motion of both ions is crucial for maintaining a flexible metal
      centered structural architecture exquisitely tailored to accommodate the DNA or
      RNA sugar-phosphate backbone during phosphodiester bond cleavage. Furthermore,
      our analysis of RNase H and the N-terminal domain (PAN) of influenza polymerase
      shows that classical molecular dynamics simulations coupled with enhanced
      sampling techniques have contributed to describe the modulatory effect of metal
      ion concentration and metal uptake on the 2M mechanism and efficiency. These
      aspects all point to the emerging and intriguing role of additional adjacent ions
      potentially involved in the modulation of phosphoryl transfer reactions and
      enzymatic turnover in 2M-catalysis, as recently observed experimentally in
      polymerase eta and homing endonuclease I-DmoI. These computational results,
      integrated with experimental findings, describe and reinforce the nascent concept
      of a functional and cooperative dynamics of the catalytic metal ions during the
      2M-dependent enzymatic processing of DNA and RNA. Encouraged by the insights
      provided by computational approaches, we foresee further experiments that will
      feature the functional and joint dynamics of the catalytic metal ions for nucleic
      acid processing. This could impact the de novo design of artificial
      metallonucleases and the rational design of potent metal-chelating inhibitors of
      pharmaceutically relevant enzymes.

PMID- 25590655
TI  - Proof of concept study for designed multiple ligands targeting the dopamine D2,
      serotonin 5-HT2A, and muscarinic M1 acetylcholine receptors.
AB  - Herein we describe the hybridization of a benzoxazinone M1 scaffold with D2
      privileged structures derived from putative and clinically relevant
      antipsychotics to develop designed multiple ligands. The M1 mAChR is an
      attractive target for the cognitive deficits in key CNS disorders. Moreover,
      activity at D2 and 5-HT2A receptors has proven useful for antipsychotic efficacy.
      We identified 9 which retained functional activity at the target M1 mAChR and D2R
      and demonstrated high affinity for the 5-HT2AR. 

PMID- 25590656
TI  - Application of fluorescent nanoparticles to study remodeling of the endo
      lysosomal system by intracellular bacteria.
AB  - Fluorescent nanoparticles (NPs) with desirable chemical, optical and mechanical
      properties are promising tools to label intracellular organelles. Here, we
      introduce a method using gold-BSA-rhodamine NPs to label the endo-lysosomal
      system of eukaryotic cells and monitor manipulations of host cellular pathways by
      the intracellular pathogen Salmonella enterica. The NPs were readily internalized
      by HeLa cells and localized in late endosomes/lysosomes. Salmonella infection
      induced rearrangement of the vesicles and accumulation of NPs in Salmonella
      induced membrane structures. We deployed the Imaris software package for
      quantitative analyses of confocal microscopy images. The number of objects and
      their size distribution in non-infected cells were distinct from the ones in
      Salmonella-infected cells, indicating extremely remodeling of the endo-lysosomal
      system by WT Salmonella. 

PMID- 25590658
TI  - A scalp lesion with intracranial extension. Atretic cephalocele.

PMID- 25590657
TI  - Epigenome-wide analysis of piRNAs in gene-specific DNA methylation.
AB  - PIWI-interacting RNAs (piRNAs) have long been associated with the silencing of
      transposable elements (TEs). However, over 20,000 unique species of piRNAs mapped
      to the human genome are more than the relatively few presumably required to
      regulate the known human transposon classes. Here, we present the results of the
      first genome-wide effort to study the effects of piRNAs on gene specific DNA
      methylation. We found that exon-derived piRNAs consist almost universally of
      species with 10 or fewer genomic copies, whereas piRNAs existing in high copies
      originate predominately from intronic and intergenic regions. Genome-wide
      methylation profiling following transfection of human somatic cells with piRNA
      mimics revealed methylation changes at numerous genic loci in single copy piRNA
      transfected cells. Moreover, genomic regions directly adjacent to differentially
      methylated CpG sites were enriched for sequence matches to the transfected
      piRNAs. These findings suggest that a subset of single copy piRNAs may be able to
      induce DNA methylation at non-TE genic loci, a process that may be mediated in
      part by direct binding to either genomic DNA or nascent mRNA near target CpG
      sites. 

PMID- 25590659
TI  - When is feeding via a percutaneous endoscopic gastrostomy indicated?
AB  - PURPOSE OF REVIEW: This review addresses current controversies regarding
      appropriate indications for percutaneous endoscopic gastrostomy (PEG) insertion.
      We address specific indications, namely, dementia, stroke, aspiration, motor
      neurone disease/amyotrophic lateral sclerosis, and head and neck cancer. We
      recommend practical strategies for improving patient selection. RECENT FINDINGS:
      There is now a general consensus in the United States that PEG feeding does not
      benefit patients with advanced dementia. 'Early' PEG insertion following stroke
      is similarly of no benefit. It is currently unclear whether patients with
      amyotrophic lateral sclerosis and head and neck tumors should have PEG or
      radiologically inserted gastrostomy. SUMMARY: Decisions relating to PEG insertion
      remain difficult. The gastroenterologist, working as a member of a
      multidisciplinary nutrition team, needs to take a lead role in this regard,
      rather than functioning as a technician.

PMID- 25590661
TI  - TCTEX1D2, a potential link to skeletal ciliopathies.

PMID- 25590660
TI  - Empirical caspofungin therapy in clinical practice for suspected invasive fungal
      disease in adults with acute lymphoblastic leukaemia.
AB  - Patients with acute lymphoblastic leukaemia (ALL) after cytotoxic chemotherapy or
      haematopoietic stem cell transplantation (HSCT) are at risk for life-threatening
      invasive fungal disease (IFD). The aim was to evaluate the characteristics,
      antifungal therapy and outcome of adult patients with ALL after chemotherapy or
      HSCT receiving caspofungin empirically in a clinical setting. Retrospective chart
      reviews were conducted at nine large tertiary care centres in Germany. Adult
      patients with ALL treated empirically with caspofungin according to the product
      label between 2006 and 2012 were eligible. Data were extracted as case reports.
      In total, 25 patients (12 males, 13 females; median age 37 years; 19 with B-ALL,
      6 with T-ALL) with 28 treatment episodes because of suspected IFD (18 episodes
      after chemotherapy, 10 episodes after allogeneic HSCT) were included in the
      analysis. Empirical caspofungin therapy (median duration: 19 days, range 1-105
      days) was given as first-line monotherapy in 20 (71.4%), second-line monotherapy
      in five (17.9%) and combination therapy in three (10.7%) episodes respectively.
      Therapy rated successful according to the physician's overall assessment
      (inflammatory parameters, clinical symptoms): 20 (95%) of 21 evaluable episodes
      with therapy duration of at least 8 days. Empirical caspofungin appears to be an
      effective therapeutic option in critically ill adult ALL patients with suspected
      IFD in clinical practice. 

PMID- 25590662
TI  - Disease outcomes for skull base and spinal chordomas: a single center experience.
AB  - OBJECTIVE: Chordomas carry significant morbidity due to their growth patterns and
      surgical constraints in resection. En bloc resection, when feasible, is the ideal
      treatment goal, but is associated with significant morbidity. We sought to
      elucidate the relationship between extent of surgery, location and radiotherapy
      in relation to overall disease and progression free survival (PFS). METHODS: We
      reviewed case records for all patients with a primary histopathological diagnosis
      of clival and spinal chordomas that was presented to our institution between 1978
      and 2010. RESULTS: A total of 49 patients (location: n=30, skull base/clival;
      n=12 vertebral column; n=7 sacrum) were identified with mean follow-up period of
      6.3 years (range 0.25 months-33 years). Improved 5 year and 10 year survival
      rates were noted following gross total resection (n=8, 5 year and 10 year
      survival=88%) as compared to patients that underwent subtotal resection (n=41,
      55% and 31%, respectively), (p-value>0.05, GTR versus STR). Adjuvant high-dose
      stereotactic fractionated radiotherapy (HS-FSRT) significantly improved 5 year
      PFS in craniocervical chordoma patients (70%, n=13) as compared to standard dose
      radiation therapy (20%, n=16; p-value=0.03). Overall 10 year survival for
      craniocervical patients undergoing HD-FSRT (40%) was however not significantly
      different in comparison with conventional radiotherapy (45%). Sacral chordomas
      had the worst prognosis with 3 year survival of 28.6%. CONCLUSIONS: GTR offers
      the best prognosis for improved long-term survival. Adjuvant HD FSRT for cranio
      cervical/clival chordomas significantly improves disease free survival though the
      long-term benefits on survival have yet to be established. Sacral chordomas are
      associated with a worse prognosis and poor long-term survival.

PMID- 25590663
TI  - Brain metabolism assessed via proton magnetic resonance spectroscopy in patients
      with amnestic or vascular mild cognitive impairment.
AB  - BACKGROUND AND OBJECTIVES: To address the possible role of brain regional
      metabolic differences between different types of mild cognitive impairment (MCI).
      PATIENTS AND METHODS: Brain regional metabolites in patients with amnestic mild
      cognitive impairment (A-MCI) and vascular mild cognitive impairment (V-MCI) were
      measured via proton magnetic resonance spectroscopy (1H MRS) technique. Twenty
      eight patients with A-MCI, 24 patients with V-MCI and 34 normal controls (NC)
      were tested by a battery of neuropsychological screens. All the subjects
      underwent the single voxel 1H MRS with the regions of interest (ROIs) located in
      the left frontal lobe, left basal ganglia and left hippocampus. RESULTS: The A
      MCI showed lower NAA/Cr ratio in the left hippocampus. There was a significant
      correlation between recent memory score and the NAA/Cr ratio. In V-MCI, NAA/Cr
      ratio in the left frontal lobe was positively correlated with the cognitive score
      evaluated with Cambridge Cognitive Examination-Chinese version (CAMCOG-C) and its
      subscores of orientation, praxi, language and language comprehension.
      CONCLUSIONS: This study indicated that there are differences in metabolism
      related to brain regions between A-MCI and V-MCI, thus it may be concluded that
      1H MRS may be a useful tool to differentiate A-MCI and V-MCI.

PMID- 25590664
TI  - Ommaya reservoir with ventricular catheter placement for chemotherapy with
      frameless and pinless electromagnetic surgical neuronavigation.
AB  - BACKGROUND: Accuracy in Ommaya reservoir catheter placement is critical to
      chemotherapy infusion. Most frameless image guidance is light emitting diode
      (LED) based, requiring a direct line of communication between instrument and
      tracker, limiting freedom of instrument movement within the surgical field.
      Electromagnetic neuronavigation may overcome this challenge. OBJECTIVE: To
      compare Ommaya reservoir ventricular catheter placement using electromagnetic
      neuronavigation to LED-based optical navigation, with emphasis on placement
      accuracy, operative time and complication rate. METHODS: Twenty-eight patients
      who underwent placement of Ommaya reservoirs at our institution between 2010 and
      2014 with either electromagnetic (12 patients) or optical neuronavigation (16
      patients) were retrospectively reviewed. RESULTS: Half of the patients were male.
      Their mean age was 56 years (range 28-87 years). Accuracy and precision in
      catheter tip placement at the target site (foramen of Monro) were both higher
      (p=0.038 and p=0.043, respectively) with electromagnetic neuronavigation.
      Unintended placement of the distal catheter contralateral to the target site
      occurred more frequently with optical navigation, as did superior or inferior
      positioning by more than 5 mm. Mean operative times were shorter (p=0.027) with
      electromagnetic neuronavigation (43.2 min) than with optical navigation (51.0
      min). There were three complications (10.7%)--one case each of cytotoxic edema,
      post-operative wound infection, and urinary tract infection. The rate of
      complication did not differ between groups. CONCLUSION: In contrast with optical
      neuronavigation, frameless and pinless electromagnetic image guidance allows the
      ability to track instrument depth in real-time. It may increase ventricular
      catheter placement accuracy and precision, and decrease operative times.

PMID- 25590665
TI  - Changing the needle for lumbar punctures: results from a prospective study.
AB  - OBJECTIVE: Post-dural puncture headache (PDPH) is a common complication of
      diagnostic lumbar punctures. Both a non-cutting needle design and the use of
      smaller size needles have been shown to greatly reduce the risk of PDPH.
      Nevertheless, larger cutting needles are still widely used. This study describes
      the process of changing the needle in an outpatient clinic of a Danish neurology
      department. METHODS: Prospective interventional trial. Phase 1: 22G cutting
      needle. Phase 2: 25G non-cutting needle. Practical usability of each needle was
      recorded during the procedure, while the rate of PDPH and the occurrence of
      socioeconomic complications were acquired from a standardized questionnaire.
      RESULTS: 651 patients scheduled for diagnostic lumbar punctures were screened for
      participation and 501 patients were included. The response rate was 80% in both
      phases. In phase 2, significant reductions were observed in occurrence of PDPH
      (21 vs. 50, p=0.001), number of days spent away from work (55 vs. 175, p<0.001),
      hospitalizations (2 vs. 17, p<0.001), and number of bloodpatch treatments (2 vs.
      10, p=0.019). Furthermore, during the procedure, both the need for multiple
      attempts (30% vs. 44%, p=0.001), and the failure-rate of the first operator (17%
      vs. 29%, p=0.005) were reduced. CONCLUSIONS: Our study showed that smaller, non
      cutting needles reduce the incidence of PDPH and are easily implemented in an
      outpatient clinic. Changing the needle resulted in fewer socioeconomic
      complications and fewer overall costs, while also reducing procedural difficulty.

PMID- 25590666
TI  - Are we able to predict survival in ER-positive HER2-negative breast cancer? A
      comparison of web-based models.
AB  - BACKGROUND: Several prognostic models have been proposed and demonstrated to be
      predictive of survival outcomes in breast cancer. In the present article, we
      assessed whether three of these models are comparable at an individual level.
      METHODS: We used a large data set (n=965) of women with hormone receptor-positive
      and HER2-negative early breast cancer from the public data set of the METABRIC
      (Molecular Taxonomy of Breast Cancer International Consortium) study. We compared
      the overall performance of three validated web-based models: Adjuvant!,
      CancerMath.net and PREDICT, and we assessed concordance of these models in 10
      year survival prediction. RESULTS: Discrimination performances of the three
      calculators to predict 10-year survival were similar for the Adjuvant! Model,
      0.74 (95% CI 0.71-0.77) for the Cancermath.net model and 0.72 (95% CI 0.69-0.75)
      for the PREDICT model). Calibration performances, assessed graphically, were
      satisfactory. Predictions were concordant and stable in the subgroup, with a
      predicted survival higher than 90% with a median score dispersion at 0.08 (range
      0.06-0.10). Dispersion, however, reached 30% for the subgroups with a predicted
      survival between 10 and 50%. CONCLUSION: This study revealed that the three web
      based predictors equally perform well at the population level, but exhibit a high
      degree of discordance in the intermediate and poor prognosis groups.

PMID- 25590669
TI  - An investigation into motorcycle crashes in work zones.
AB  - OBJECTIVE: There were 454 motorcycle crashes in work zones within the state of
      Ohio between January 2006 and July 2012. Pavement degradation derived from work
      zones tend to have a hazardous effect on motorcycles and their safe passage. The
      objective of this study is to research the work zones where motorcycle crashes
      have taken place in order to determine any contributing factors. METHODS: This
      study incorporates the collection of motorcycle crash data, including
      construction documents associated with the work zones in which the crashes
      occurred. Crash documents from the Ohio Department of Public safety and the Ohio
      Department of Transportation are used to identify the initial factors to be
      studied. RESULTS: Construction documents associated with 183 of the crashes are
      able to be retrieved. From these documents, the frequency of associated crashes
      and rates of fatalities per work type are able to be determined. CONCLUSIONS: It
      is found that work types that take place on lower functional class roadways, such
      as sewer repair, are found to have higher fatality rates. In contrast, those work
      zones on higher functional class roadways often incorporate speed calming
      measures and have a clear division between the traveled way and the actual
      construction work.

PMID- 25590667
TI  - Television watching and risk of colorectal adenoma.
AB  - BACKGROUND: Prolonged TV watching, a major sedentary behaviour, is associated
      with increased risk of obesity and diabetes and may involve in colorectal
      carcinogenesis. METHODS: We conducted a cross-sectional analysis among 31 065 men
      with ?1 endoscopy in the Health Professionals Follow-up Study (1988-2008) to
      evaluate sitting while watching TV and its joint influence with leisure-time
      physical activity on risk of colorectal adenoma. Logistic regression was used to
      calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:
      Prolonged sitting while watching TV was significantly associated with increased
      risk of colorectal adenoma (n=4280), and adjusting for physical activity or a
      potential mediator body mass index did not change the estimates. The ORs (95%
      CIs) across categories of TV watching (0-6, 7-13, 14-20, and 21+ h per week) were
      1.00 (referent), 1.09 (1.01-1.17), 1.16 (1.06-1.27), and 1.10 (0.97-1.25) (OR per
      14-h per week increment=1.11; 95% CI: 1.04-1.18; Ptrend=0.001). Compared with the
      least sedentary (0-6 h per week of TV) and most physically active (highest
      quintile) men, the most sedentary (14+ h per week) and least active (lowest
      quintile) men had a significant increased risk of adenoma (OR=1.25; 95% CI: 1.05
      1.49), particularly for high-risk adenoma. CONCLUSIONS: Prolonged TV viewing is
      associated with modest increased risk of colorectal adenoma independent of
      leisure-time physical activity and minimally mediated by obesity.

PMID- 25590668
TI  - Racial/Ethnic variation in all-cause mortality among United States medicaid
      recipients with systemic lupus erythematosus: a Hispanic and asian paradox.
AB  - OBJECTIVE: The incidence of systemic lupus erythematosus (SLE) is
      disproportionately high in nonwhite patients compared with white patients.
      However, variation in mortality according to race/ethnicity has not been well
      studied. The aim of this study was to examine all-cause mortality according to
      race/ethnicity among SLE patients enrolled in Medicaid. METHODS: We used Medicaid
      Analytic eXtract data, with billing claims from 47 US states and Washington, DC,
      to identify individuals ages 18-65 years who were enrolled in Medicaid for >=3
      months in 2000-2006. Individuals were classified as having SLE if they had >=3
      visits >=30 days apart with an International Classification of Diseases, Ninth
      Revision (ICD-9) code for SLE (710.0). Among the individuals with SLE, those with
      lupus nephritis (LN) were identified by the presence of >=2 ICD-9 claims for
      glomerulonephritis, proteinuria, or renal failure. We calculated mortality rates
      per 1,000 person-years, with 95% confidence intervals (95% CIs), according to
      race/ethnicity. Multivariable Cox proportional hazards regression models were
      used to estimate mortality risks, adjusting for age, sex, demographics, and
      comorbidities. RESULTS: Among 42,221 prevalent cases of SLE, 8,191 prevalent
      cases of LN were identified. Blacks represented 40.1%, whites 38.4%, and
      Hispanics 15.3%. Overall SLE mortality rates per 1,000 person-years were highest
      among Native American (27.52), white (20.17), and black (24.13) patients and were
      lower among Hispanic (7.12) or Asian (5.18) patients. After multivariable
      adjustment, Hispanic and Asian patients had lower mortality risks (hazard ratio
      [HR] 0.48 [95% CI 0.40-0.59] and 0.59 [95% CI 0.40-0.86], respectively) compared
      with whites. Conversely, the risk of death was significantly higher among Native
      American (HR 1.40 [95% CI 1.04-1.90]) and black (HR 1.21 [95% CI 1.10-1.33])
      patients compared with white patients. Among patients with LN, mortality risks
      were lower in Hispanic and Asian patients compared with white patients.
      CONCLUSION: After accounting for demographic and clinical factors, mortality
      among Asian and Hispanic Medicaid patients with SLE was lower than that among
      black, white, or Native American patients.

PMID- 25590670
TI  - Simultaneous orthogonal dual-click approach to tough, in-situ-forming hydrogels
      for cell encapsulation.
AB  - The use of tough hydrogels as biomaterials is limited as a consequence of time
      consuming fabrication techniques, toxic starting materials, and large strain
      hysteresis under deformation. Herein, we report the simultaneous application of
      nucleophilic thiol-yne and inverse electron-demand Diels-Alder additions to
      independently create two interpenetrating networks in a simple one-step
      procedure. The resultant hydrogels display compressive stresses of 14-15 MPa at
      98% compression without fracture or hysteresis upon repeated load. The hydrogel
      networks can be spatially and temporally postfunctionalized via radical
      thiylation and/or inverse electron-demand Diels-Alder addition to residual
      functional groups within the network. Furthermore, gelation occurs rapidly under
      physiological conditions, enabling encapsulation of human cells. 

PMID- 25590671
TI  - Role of vibrational dynamics in electronic relaxation of Cr(acac)3.
AB  - Ultrafast energy relaxation of Cr(acac)3 dissolved in tetrachloroethylene (TCE)
      is studied by time-resolved infrared (TRIR) spectroscopy by using electronic and
      vibrational excitation. After electronic excitation at 400 or 345 nm, the ground
      state recovers in two time scales: 15 ps (major pathway) and 800 ps (minor
      pathway), corresponding to fast electronic transition to the ground state and
      intermediate trapping on the long-lived (2)E state followed by intersystem
      crossing (ISC) to the ground state. The quantum yield for the fast recovery of
      the ground state depends on the excitation wavelength, being higher for 345 nm.
      Vibrational cooling (VC) occurs on the electronic excited states with a time
      constant of ~7 ps and on the ground electronic state with a time constant of ~12
      ps. A kinetic model that explains the observed dynamics is presented. The key
      point of the model is that the ground-state recovery occurs via thermally
      activated back-intersystem-crossing (b-ISC) to the quartet manifold presumably
      via multiple curve crossings that are sampled while the system is vibrationally
      hot. This underlines the importance of vibrational cooling as a determining
      factor for the electronic relaxation chain. Vibrational excitation of the nuC?C
      and nuCO vibrations also revealed a subpicosecond (300-700 fs) intramolecular
      vibrational redistribution (IVR) process from the localized vibrational states to
      the bath of vibrational excitations. 

PMID- 25590672
TI  - Total synthesis of the cyclic depsipeptide YM-280193, a platelet aggregation
      inhibitor.
AB  - The first total synthesis of YM-280193, a cyclic depsipeptide that inhibits the
      ADP-induced aggregation of human platelets, is described. The monomer and
      dipeptide fragments were prepared using conventional chemistry and subsequently
      assembled by Fmoc-solid-phase peptide synthesis (Fmoc-SPPS). A late-stage novel
      bis-alkylation-elimination of cysteine on-resin was employed to introduce the
      unnatural N-methyldehydroalanine moiety. The final step involved execution of a
      key macrolactamization reaction between the hindered unnatural N,O
      dimethylthreonine and beta-hydroxyleucine residues. 

PMID- 25590673
TI  - Detoxification of chlorella supplement on heterocyclic amines in Korean young
      adults.
AB  - Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) have been
      established as carcinogenic chemicals in Western diet. This study was performed
      to estimate HCA exposure levels in Korean daily life and to assess the ability of
      Chlorella vulgaris to detoxify carcinogenic HCAs in a randomized, double blind,
      placebo-controlled crossover study with chlorella supplement (N=6, all females,
      age: 27.17+/-7.73yr) for 2 weeks. We analyzed HCAs in hydrolyzed urine specimens
      using LC/TOF-MS. As results, urinary levels of MeIQx, PhIP, and IQx-8-COOH were
      323.36+/-220.11ng/L, 351.59+/-254.93ng/L, and 130.85+/-83.22ng/L, respectively.
      Effects of chlorella to reduce urinary MeIQx were marginally significant (before,
      430+/-226.86pg/mL vs. after, 174.45+/-101.65pg/mL: 0.05<p<0.1). However, urinary
      levels of PhIP or IQx-8-COOH, a major metabolite of MeIQx, were not changed by
      chlorella supplementation. In conclusion, our study demonstrates that current
      daily levels of HCA exposure in Korean young adults are not lower than those in
      the Western world. In addition, the effects of chlorella's to detoxify HCAs
      likely occur by interfering e with absorption or metabolism. 

PMID- 25590674
TI  - Implementation and evaluation of data analysis strategies for time-resolved
      optical spectroscopy.
AB  - Time-resolved optical spectroscopy plays a key role in illuminating the
      mechanisms of many fundamental processes in physics, chemistry, and biology.
      However, to extract the essential information from the highly complex time
      resolved data, advanced data analysis techniques are required. Here we present
      the implementation strategies and the evaluation of the familiar global lifetime
      and target analysis as well as the not so widely adopted lifetime distribution
      analysis (LDA). Furthermore, we demonstrate the implementation of analysis
      strategies dealing with a number of artifacts inherently present in data from
      ultrafast optical experiments. The focus of the work is placed on LDA as it
      allows invaluable exploration depth of the kinetic information contained in the
      experimental data. We establish a clear regularization procedure for the use of
      LDA in ultrafast optical spectroscopy and evaluate the performance of a number of
      factors that play a role in the reliable reconstruction of lifetime
      distributions. Our results show that the optimal regularization factor can be
      determined well with the L-curve and the generalized cross-validation techniques.
      Moreover, the performance evaluations indicate that the most efficient
      regularization norm is the identity matrix. The analytical procedures described
      in this work can be readily implemented and used for the analysis of any time
      resolved data. 

PMID- 25590675
TI  - An index for measuring overuse of health care resources with Medicare claims.
AB  - BACKGROUND: Overuse can be defined as use of a service when the risk of harm
      exceeds its likely benefit. Yet, there has been little work with composite
      measures of overuse. OBJECTIVE: Our goal was to create a composite measure of
      overuse with claims data. DESIGN: Observational study using 5% of Medicare claims
      from 2008. SETTING: All inpatient and outpatient settings of care, excluding
      nursing homes. PARTICIPANTS: Older Americans receiving health care services in
      hospitals or outpatient settings. MEASURES: We applied algorithms to identify
      specific cases of overuse across 20 previously identified procedures and used
      multilevel modeling techniques to examine variation in overuse across all
      procedures. Included in the model were patient-level factors and both procedure
      and regional fixed effects for the 306 hospital referral regions (HRR). These
      estimated regional fixed effects, representing the systematic, region variation
      in overuse across all measures, was then normalized compared with the overall
      average to generate a Z score for each HRR. The resulting "Overuse Index" was
      then compared with total costs, 30-day postdischarge mortality, and total
      mortality at the HRR level, graphically, and associations were tested using
      Spearman rho. RESULTS: The Overuse Index varied markedly across regions, but 23
      were higher than the average (P<0.05). The Index was positively associated with
      total costs (rho=0.28, P<0.0001). It was positively correlated with 30-day
      postdischarge mortality (rho=0.18 P<=0.005), and neither positively or negatively
      correlated with total mortality. CONCLUSIONS: This study confirms previous
      research hypothesizing that systematic regional variation in overuse exists and
      is measurable. Addition research is needed to validate index and to test its
      predictive and concurrent validity in panel data.

PMID- 25590677
TI  - Controversies in the management of feline urethral obstruction.
AB  - OBJECTIVE: To discuss areas of differing opinion in the management of feline
      urethral obstruction and present current evidence to either support or refute
      common practices. ETIOLOGY: Urethral obstruction may occur as a result from a
      functional obstruction (idiopathic obstruction) or a physical obstruction, such
      as mucous plugs or calculi within the urethra. Potential risk factors for
      obstruction in cats include predominantly indoor status, decreased water intake,
      and increased body weight. DIAGNOSIS: The diagnosis is most commonly made based
      on history and initial physical exam-straining to urinate, vocalizing, signs of
      systemic illness, moderate to large firm bladder on abdominal palpation. THERAPY:
      Treatment is based on available evidence. The type of IV isotonic crystalloid
      used does not seem to matter and rate should be determined by need for fluid
      resuscitation, and replacement of deficit and ongoing losses. Though
      controversial, cystocentesis appears to be safe and may offer some benefits in
      initial management. There is evidence to suggest a smaller urethral catheter (3.5
      Fr) may be associated with decreased risk of reobstruction. Routine use of
      antimicrobial agents in hospital is not recommended; they should be dispensed
      based on culture performed at the time of catheter removal. Though commonly used,
      evidence in support of antispasmodics is limited and further prospective
      investigation is needed. PROGNOSIS: Feline urethral obstruction is associated
      with 90-95% survival, with reported recurrence rates of 15-40%. Potential factors
      affecting recurrence include size or duration of indwelling urinary catheter, use
      of antispasmodic agents, patient age, and indoor-outdoor lifestyle; however,
      different studies offer conflicting results. Increased water intake and
      environmental modification do seem to decrease risk of recurrence.

PMID- 25590676
TI  - Quantifying the economic value and quality of life impact of earlier influenza
      vaccination.
AB  - BACKGROUND: Influenza vaccination is administered throughout the influenza
      disease season, even as late as March. Given such timing, what is the value of
      vaccinating the population earlier than currently being practiced? METHODS: We
      used real data on when individuals were vaccinated in Allegheny County,
      Pennsylvania, and the following 2 models to determine the value of vaccinating
      individuals earlier (by the end of September, October, and November): Framework
      for Reconstructing Epidemiological Dynamics (FRED), an agent-based model (ABM),
      and FluEcon, our influenza economic model that translates cases from the ABM to
      outcomes and costs [health care and lost productivity costs and quality-adjusted
      life-years (QALYs)]. We varied the reproductive number (R0) from 1.2 to 1.6.
      RESULTS: Applying the current timing of vaccinations averted 223,761 influenza
      cases, $16.3 million in direct health care costs, $50.0 million in productivity
      losses, and 804 in QALYs, compared with no vaccination (February peak, R0 1.2).
      When the population does not have preexisting immunity and the influenza season
      peaks in February (R0 1.2-1.6), moving individuals who currently received the
      vaccine after September to the end of September could avert an additional 9634
      17,794 influenza cases, $0.6-$1.4 million in direct costs, $2.1-$4.0 million in
      productivity losses, and 35-64 QALYs. Moving the vaccination of just children to
      September (R0 1.2-1.6) averted 11,366-1660 influenza cases, $0.6-$0.03 million in
      direct costs, $2.3-$0.2 million in productivity losses, and 42-8 QALYs. Moving
      the season peak to December increased these benefits, whereas increasing
      preexisting immunity reduced these benefits. CONCLUSION: Even though many people
      are vaccinated well after September/October, they likely are still vaccinated
      early enough to provide substantial cost-savings.

PMID- 25590678
TI  - Updated estimates of neural tube defects prevented by mandatory folic Acid
      fortification - United States, 1995-2011.
AB  - In 1992, the U.S. Public Health Service recommended that all women capable of
      becoming pregnant consume 400 ug of folic acid daily to prevent neural tube
      defects (NTDs). NTDs are major birth defects of the brain and spine that occur
      early in pregnancy as a result of improper closure of the embryonic neural tube,
      which can lead to death or varying degrees of disability. The two most common
      NTDs are anencephaly and spina bifida. Beginning in 1998, the United States
      mandated fortification of enriched cereal grain products with 140 ug of folic
      acid per 100 g. Immediately after mandatory fortification, the birth prevalence
      of NTD cases declined. Fortification was estimated to avert approximately 1,000
      NTD-affected pregnancies annually. To provide updated estimates of the birth
      prevalence of NTDs in the period after introduction of mandatory folic acid
      fortification (i.e., the post-fortification period), data from 19 population
      based birth defects surveillance programs in the United States, covering the
      years 1999-2011, were examined. After the initial decrease, NTD birth prevalence
      during the post-fortification period has remained relatively stable. The number
      of births occurring annually without NTDs that would otherwise have been affected
      is approximately 1,326 (95% confidence interval = 1,122-1,531). Mandatory folic
      acid fortification remains an effective public health intervention. There remain
      opportunities for prevention among women with lower folic acid intakes,
      especially among Hispanic women, to further reduce the prevalence of NTDs in the
      United States.

PMID- 25590679
TI  - Supplement use and other characteristics among pregnant women with a previous
      pregnancy affected by a neural tube defect - United States, 1997-2009.
AB  - Neural tube defects (NTDs) include anomalies of the brain (anencephaly and
      encephalocele) and spine (spina bifida). Even with ongoing mandatory folic acid
      fortification of enriched cereal grain products, the U.S. Preventive Services
      Task Force recommends that women of childbearing potential consume a daily
      supplement containing 400 ug-800 ug of folic acid. Women with a prior NTD
      affected pregnancy have an increased risk for having another NTD-affected
      pregnancy, and if they are planning another pregnancy, the recommendation is that
      they consume high-dosage folic acid supplements (4.0 mg/day) beginning >=4 weeks
      before conception and continuing through the first 12 weeks of pregnancy. To
      learn whether folic acid supplementation (from multivitamins or single-
      ingredient supplements) was commonly used during pregnancy by women with a
      previous NTD-affected pregnancy, supplement use was assessed among a convenience
      sample of women with a previous NTD-affected pregnancy who participated in the
      National Birth Defects Prevention Study (NBDPS), a case-control study of major
      birth defects in the United States. Characteristics of women who previously had
      an NTD-affected pregnancy and whose index pregnancy (pregnancy included in NBDPS)
      was either affected by an NTD (N = 17) (i.e., recurrence-cases) or resulted in a
      live-born infant without a major birth defect (N = 10) (i.e., recurrence
      controls) were assessed. Taking a supplement that included folic acid was more
      common among recurrence-control mothers (80%) than recurrence-case mothers (35%).
      The recommendation that women should take folic acid supplements just before and
      during early pregnancy is not being followed by many women and offers an
      opportunity for NTD prevention, especially among women who are at a higher risk
      because they have had a previous pregnancy affected by an NTD. 

PMID- 25590680
TI  - Early estimates of seasonal influenza vaccine effectiveness - United States,
      January 2015.
AB  - In the United States, annual vaccination against seasonal influenza is
      recommended for all persons aged >=6 months. Each season since 2004-05, CDC has
      estimated the effectiveness of seasonal influenza vaccine in preventing medically
      attended acute respiratory illness (ARI) associated with laboratory-confirmed
      influenza. This season, early estimates of influenza vaccine effectiveness are
      possible because of widespread, early circulation of influenza viruses. By
      January 3, 2015, 46 states were experiencing widespread flu activity, with
      predominance of influenza A (H3N2) viruses. This report presents an initial
      estimate of seasonal influenza vaccine effectiveness at preventing laboratory
      confirmed influenza virus infection associated with medically attended ARI based
      on data from 2,321 children and adults enrolled in the U.S. Influenza Vaccine
      Effectiveness Network (Flu VE) during November 10, 2014-January 2, 2015. During
      this period, overall vaccine effectiveness (VE) (adjusted for study site, age,
      sex, race/ethnicity, self-rated health, and days from illness onset to
      enrollment) against laboratory-confirmed influenza associated with medically
      attended ARI was 23% (95% confidence interval [CI] = 8%-36%). Most influenza
      infections were due to A (H3N2) viruses. This interim VE estimate is relatively
      low compared with previous seasons when circulating viruses and vaccine viruses
      were well-matched and likely reflects the fact that more than two-thirds of
      circulating A (H3N2) viruses are antigenically and genetically different
      (drifted) from the A (H3N2) vaccine component of 2014-15 Northern Hemisphere
      seasonal influenza vaccines. These early, low VE estimates underscore the need
      for ongoing influenza prevention and treatment measures. CDC continues to
      recommend influenza vaccination because the vaccine can still prevent some
      infections with the currently circulating A (H3N2) viruses as well as other
      viruses that might circulate later in the season, including influenza B viruses.
      Even when VE is reduced, vaccination still prevents some illness and serious
      influenza-related complications, including thousands of hospitalizations and
      deaths. Persons aged >=6 months who have not yet been vaccinated this season
      should be vaccinated, including persons who might already have been ill with
      influenza this season.

PMID- 25590681
TI  - Incidence of notifiable diseases among American Indians/Alaska Natives - United
      States, 2007-2011.
AB  - American Indian/Alaska Native (AI/AN) populations experience substantial
      disparities in the incidence of multiple diseases compared with other
      racial/ethnic groups in the United States. A major goal of Healthy People 2020 is
      to eliminate health disparities, monitor disease trends, and identify population
      groups and diseases for targeted interventions. High rates of certain infectious
      diseases continue to be a major problem facing AI/AN populations. During 1990
      2011, incidence rates for some infectious diseases declined among AI/AN
      populations, but disparities remain and AI/AN populations are still
      disproportionately affected. To describe disparities in selected notifiable
      diseases among AI/ANs, CDC analyzed data from the National Notifiable Diseases
      Surveillance System (NNDSS) for 2007-2011, the most recent 5 years for which data
      are available. The results of this analysis of 26 infectious diseases indicate
      that incidence rates of 14 diseases were higher for AI/ANs than for whites.
      Interventions are needed to address and reduce disparities in chlamydia,
      gonorrhea, West Nile virus, spotted fever rickettsiosis, and other infections
      among AI/ANs. 

PMID- 25590682
TI  - Improving burial practices and cemetery management during an Ebola virus disease
      epidemic - Sierra Leone, 2014.
AB  - As of January 3, 2015, Ebola virus disease (Ebola) has killed more than 2,500
      persons in Sierra Leone since the epidemic began there in May 2014. Ebola virus
      is transmitted principally by direct physical contact with an infected person or
      their body fluids during the later stages of illness or after death. Contact with
      the bodies and fluids of persons who have died of Ebola is especially common in
      West Africa, where family and community members often touch and wash the body of
      the deceased in preparation for funerals. These cultural practices have been a
      route of Ebola transmission. In September 2014, CDC, in collaboration with the
      Sierra Leone Ministry of Health and Sanitation (MOH), assessed burial practices,
      cemetery management, and adherence to practices recommended to reduce the risk
      for Ebola virus transmission. The assessment was conducted by directly observing
      burials and cemetery operations in three high-incidence districts. In addition, a
      community assessment was conducted to assess the acceptability to the population
      of safe, nontraditional burial practices and cemetery management intended to
      reduce the risk for Ebola virus transmission. This report summarizes the results
      of these assessments, which found that 1) there were not enough burial teams to
      manage the number of reported deaths, 2) Ebola surveillance, swab collection, and
      burial team responses to a dead body alert were not coordinated, 3) systematic
      procedures for testing and reporting of Ebola laboratory results for dead bodies
      were lacking, 4) cemetery space and management were inadequate, and 5) safe
      burial practices, as initially implemented, were not well accepted by
      communities. These findings were used to inform the development of a national
      standard operating procedure (SOP) for safe, dignified medical burials, released
      on October 1. A second, national-level, assessment was conducted during October
      10-15 to assess burial team practices and training and resource needs for SOP
      implementation across all 14 districts in Sierra Leone. The national-level
      assessment confirmed that burial practices, challenges, and needs at the national
      level were similar to those found during the assessment conducted in the three
      districts. Recommendations based on the assessments included 1) district-level
      trainings on the components of the SOP and 2) rapid deployment across the 14
      districts of additional trained burial teams supplied with adequate personal
      protective equipment (PPE), other equipment (e.g., chlorine, chlorine sprayers,
      body bags, and shovels), and vehicles. Although these assessments were conducted
      very early on in the response, during October-December national implementation of
      the SOP and recommendations might have made dignified burial safer and increased
      community support for these practices; an evaluation of this observation is
      planned.

PMID- 25590683
TI  - Use of a nationwide call center for Ebola response and monitoring during a 3-day
      house-to-house campaign - Sierra Leone, September 2014.
AB  - During May 23, 2014-January 10, 2015, Sierra Leone reported 7,777 confirmed cases
      of Ebola virus disease (Ebola). In response to the epidemic, on August 5, Sierra
      Leone's Emergency Operations Center established a toll-free, nationwide Ebola
      call center. The purpose of the call center is to encourage public reporting of
      possible Ebola cases and deaths to public health officials and to provide health
      education about Ebola to callers. This information also functions as an "alert"
      system for public health officials and supports surveillance efforts for the
      response. National call center dispatchers call district-level response teams
      composed of surveillance officers and burial teams to inform them of reported
      deaths and possible Ebola cases. Members of these response teams investigate
      cases and conduct follow-up actions such as transporting ill persons to Ebola
      treatment units or providing safe, dignified medical burials as resources permit.
      The call center continues to operate. This report describes calls received during
      a 3-day national campaign and reports the results of an assessment of the call
      center operation during the campaign. 

PMID- 25590684
TI  - Notes from the field: outbreak of diarrheal illness caused by Shigella flexneri -
      American Samoa, May-June 2014.
AB  - On May 9, 2014, a physician at hospital A in American Samoa noticed an abnormally
      high number of children presenting to the emergency department with bloody
      diarrhea. Based on preliminary testing of stool specimens, Entamoeba histolytica
      infection was suspected as a possible cause. Shigella was also suspected in a
      subset of samples. On May 22, the American Samoa Department of Health requested
      assistance from CDC with the outbreak investigation. The goals of the
      investigation were to establish the presence of an outbreak, characterize its
      epidemiology and etiology, and recommend control measures. The CDC field team
      reviewed the emergency department log book for cases of diarrheal illness during
      April 15-June 13, 2014. During this period, 280 cases of diarrheal illness were
      recorded, with a peak occurring on May 10. Twice as many cases occurred during
      this period in 2014 compared with the same period in 2011, the most recent year
      for which comparable surveillance data were available. Cases were widely
      distributed across the island. The highest number of cases occurred in children
      aged 0-9 years. Across age groups, cases were similarly distributed among males
      and females. These patterns are not consistent with the epidemiology of disease
      caused by E. histolytica, which tends to cause more cases in males of all ages. 

PMID- 25590685
TI  - Ethylene and pollination decrease transcript abundance of an ethylene receptor
      gene in Dendrobium petals.
AB  - We studied the expression of a gene encoding an ethylene receptor, called
      Ethylene Response Sensor 1 (Den-ERS1), in the petals of Dendrobium orchid
      flowers. Transcripts accumulated during the young floral bud stage and declined
      by the time the flowers had been open for several days. Pollination or exposure
      to exogenous ethylene resulted in earlier flower senescence, an increase in
      ethylene production and a lower Den-ERS1 transcript abundance. Treatment with 1
      methylcyclopropene (1-MCP), an inhibitor of the ethylene receptor, decreased
      ethylene production and resulted in high transcript abundance. The literature
      indicates two kinds of ethylene receptor genes with regard to the effects of
      ethylene. One group shows ethylene-induced down-regulated transcription, while
      the other has ethylene-induced up-regulation. The present gene is an example of
      the first group. The 5' flanking region showed binding sites for Myb and myb
      like, homeodomain, MADS domain, NAC, TCP, bHLH and EIN3-like transcription
      factors. The binding site for the EIN3-like factor might explain the ethylene
      effect on transcription. A few other transcription factors (RAV1 and NAC) seem
      also related to ethylene effects. 

PMID- 25590686
TI  - Tubulin marker line of grapevine suspension cells as a tool to follow early
      stress responses.
AB  - Plant microtubules (MTs), in addition to their role in cell division and cell
      expansion, respond to various stress signals. To understand the biological
      function of this early response requires non-destructive strategies for
      visualization in cellular models that are highly responsive to stress signals. We
      have therefore generated a transgenic tubulin marker line for a cell line from
      the grapevine Vitis rupestris that readily responds to stress factors of defense
      related and abiotic stresses based on a fusion of the green fluorescent protein
      with Arabidopsis beta-tubulin 6. By a combination of spinning-disk confocal
      microscopy with quantitative image analysis, we could detect early and specific
      responses of MTs to defense-related and abiotic stress factors in vivo. We
      observed that Harpin Z (HrpZ), a bacterial elicitor that can trigger programmed
      cell death, rapidly eliminated radial MTs, followed by a slower depletion of the
      cortical array. Jasmonic acid (JA), in contrast, induced bundling of cortical
      MTs. Auxin reduced the thickness of cortical MTs. This effect followed a
      characteristic bell-shaped dose-dependency and could revert JA-induced bundling.
      Impeded cell expansion as a consequence of stress treatment or superoptimal auxin
      was linked with the appearance of intranuclear tubulin speckles. The early and
      stimulus-specific responses of MTs are discussed with respect to a function in
      processing or decoding of stress signals. 

PMID- 25590688
TI  - Assessing leukocyte-endothelial interactions under flow conditions in an ex vivo
      autoperfused microflow chamber assay.
AB  - Leukocyte-endothelial interactions are early and critical events in acute and
      chronic inflammation and can, when dysregulated, mediate tissue injury leading to
      permanent pathological damage. Existing conventional assays allow the analysis of
      leukocyte adhesion molecules only after the extraction of leukocytes from the
      blood. This requires the blood to undergo several steps before peripheral blood
      leukocytes (PBLs) can be ready for analysis, which in turn can stimulate PBLs
      influencing the research findings. The autoperfused micro flow chamber assay,
      however, allows scientists to study early leukocytes functional dysregulation
      using the systemic flow of a live mouse while having the freedom of manipulating
      a coated chamber. Through a disease model, the functional expression of leukocyte
      adhesion molecules can be assessed and quantified in a micro-glass chamber coated
      with immobilized endothelial adhesion molecules ex vivo. In this model, the blood
      flows between the right common carotid artery and left external jugular vein of a
      live mouse under anesthesia, allowing the interaction of native PBLs in the
      chamber. Real-time experimental analysis is achieved with the assistance of an
      intravital microscope as well as a Harvard Apparatus pressure device. The
      application of a flow regulator at the input point of the glass chamber allows
      comparable physiological flow conditions amongst the experiments. Leukocyte
      rolling velocity is the main outcome and is measured using the National
      Institutes of Health open-access software ImageJ. In summary, the autoperfused
      micro flow chamber assay provides an optimal physiological environment to study
      leukocytes endothelial interaction and allows researchers to draw accurate
      conclusions when studying inflammation. 

PMID- 25590689
TI  - Polyelectrolyte complexes of a cationic all conjugated fluorene-thiophene diblock
      copolymer with aqueous DNA.
AB  - We report on the structural and colorimetric effects of interaction of aqueous
      ~0.06-1% poly[9,9-bis(2-ethylhexyl)fluorene]-b-poly[3-(6
      trimethylammoniumhexyl)thiophene] bromide (PF2/6-P3TMAHT) with double-stranded
      DNA to form PF2/6-P3TMAHT(DNA)x where x is the molar ratio of DNA base pairs to
      P3TMAHT repeat units; x = 0.5 equals the nominal charge neutralization. PF2/6
      P3TMAHT forms 20-40 nm sized particles with PF2/6 core and hydrated P3TMAHT
      exterior. The polymer particles form loose one-dimensional chains giving
      micrometer long branched chains (0.19 <= x <= 0.76) and subsequently randomly
      shaped aggregates (x = 1.89) upon DNA addition. Compaction of the P3TMAHT block
      and the 20-30 nm sized core is observed for x = 0.38-0.76 and attributed to the
      DNA merged within P3TMAHT domain with this structure disassembling with DNA
      excess. Structural transformations are followed by chromic changes seen as color
      changes from deep red (x < 0.076) to yellow (x = 0.19), nearly colorless (x =
      0.38-0.76), and back to orange (x = 1.89). Both absorption and photoluminescence
      spectra display the distinct fluorene and thiophene bands and subsequent blue and
      red shifts when passing x = 0.5. Thiophene photoluminescence (PL) is
      significantly quenched by DNA with increasing x, and the changing P3TMAHT/PF2/6
      band ratio allows quantitative DNA detection. Sixteen-fold dilution does not
      change aggregate structure, but PL is blue-shifted, indicating weakened
      intermolecular interactions. 

PMID- 25590687
TI  - Neuronal cell cycle: the neuron itself and its circumstances.
AB  - Neurons are usually regarded as postmitotic cells that undergo apoptosis in
      response to cell cycle reactivation. Nevertheless, recent evidence indicates the
      existence of a defined developmental program that induces DNA replication in
      specific populations of neurons, which remain in a tetraploid state for the rest
      of their adult life. Similarly, de novo neuronal tetraploidization has also been
      described in the adult brain as an early hallmark of neurodegeneration. The aim
      of this review is to integrate these recent developments in the context of cell
      cycle regulation and apoptotic cell death in neurons. We conclude that a variety
      of mechanisms exists in neuronal cells for G1/S and G2/M checkpoint regulation.
      These mechanisms, which are connected with the apoptotic machinery, can be
      modulated by environmental signals and the neuronal phenotype itself, thus
      resulting in a variety of outcomes ranging from cell death at the G1/S checkpoint
      to full proliferation of differentiated neurons. 

PMID- 25590690
TI  - PPM1D regulates p21 expression via dephoshporylation at serine 123.
AB  - The cyclin-dependent kinase inhibitor p21 plays a critical role in regulating
      cell cycle and cell proliferation. We previously cloned the dog p21 gene and
      found that unlike human p21, dog p21 is expressed as 2 isoforms due to the
      proline-directed phosphorylation at serine 123 (S123). Here, we identified that
      PPM1D, also called Wip1 and a Mg(2+)-dependent phosphatase, dephosphorylates dog
      p21 protein at serine 123. Specifically, we showed that the level of S123
      phosphorylated dog p21 is increased by a PPM1D inhibitor in a dose-dependent
      manner. We also showed that over-expression of PPM1D decreases, whereas knockdown
      of PPM1D increases, the level of S123-phosphorylated dog p21 regardless of p53.
      Additionally, in vitro phosphatase assay was performed and showed that
      phosphorylated S123 in dog p21 is dephosphorylated by recombinant rPPM1D, which
      contains the catalytic domain of human PPM1D (residue 1-420), but not by the
      phosphatase dead rPPM1D (D314A). Furthermore, dephosphorylation of S123 by rPPM1D
      can be abrogated by PPM1D inhibitor or by withdrawal of Mg(2+). Finally, we
      showed that upon PPM1D inhibition, the level of S123-phosphorylated dog p21 was
      increased, concomitantly with decreased expression of cyclin A, cyclin B, Rb, and
      PCNA. Together, our results indicate that PPM1D functions as a phosphatase of dog
      p21 at serine 123 and plays a role in cell cycle control via p21. 

PMID- 25590692
TI  - Laser direct synthesis of silicon nanowire field effect transistors.
AB  - We demonstrate a single-step, laser-based technique to fabricate silicon nanowire
      field effect transistors. Boron-doped silicon nanowires are synthesized using a
      laser-direct-write chemical vapor deposition process, which can produce nanowires
      as small as 60 nm, far below the diffraction limit of the laser wavelength of 395
      nm. In addition, the method has the advantages of in situ doping, catalyst-free
      growth, and precise control of nanowire position, orientation, and length.
      Silicon nanowires are directly fabricated on an insulating surface and ready for
      subsequent device fabrication without the need for transfer and alignment, thus
      greatly simplifying device fabrication processes. Schottky barrier nanowire field
      effect transistors with a back-gate configuration are fabricated from the laser
      direct-written Si nanowires and electrically characterized. 

PMID- 25590691
TI  - Saponins, especially platyconic acid A, from Platycodon grandiflorum reduce
      airway inflammation in ovalbumin-induced mice and PMA-exposed A549 cells.
AB  - We investigated the inhibitory effects of Platycodon grandiflorum root-derived
      saponins (Changkil saponins: CKS) on ovalbumin-induced airway inflammation in
      mice. CKS suppressed leukocytes number, IgE, Th1/Th2 cytokines, and MCP-1
      chemokine secretion in bronchoalveolar lavage fluid. Also, ovalbumin-increased
      MUC5AC, MMP-2/9, and TIMP-1/-2 mRNA expression, NF-kappaB activation, leukocytes
      recruitment, and mucus secretion were inhibited by CKS treatment. Moreover, the
      active component of CKS, platyconic acid A (PA), suppressed PMA-induced MUC5AC
      mRNA expression (from 2.1 +/- 0.2 to 1.1 +/- 0.1) by inhibiting NF-kappaB
      activation (from 2.3 +/- 0.2 to 1.2 +/- 0.1) via Akt (from 3.7 +/- 0.3 to 2.1 +/-
      0.2) (p < 0.01) in A549 cells. Therefore, we demonstrate that CKS or PA
      suppressed the development of respiratory inflammation, hyperresponsiveness, and
      remodeling by reducing allergic responses, and they may be potential herbal drugs
      for allergen-induced respiratory disease prevention.

PMID- 25590693
TI  - Transformation of the excited state and photovoltaic efficiency of CH3NH3PbI3
      perovskite upon controlled exposure to humidified air.
AB  - Humidity has been an important factor, in both negative and positive ways, in the
      development of perovskite solar cells and will prove critical in the push to
      commercialize this exciting new photovoltaic technology. The interaction between
      CH(3)NH(3)PbI(3) and H(2)O vapor is investigated by characterizing the ground
      state and excited-state optical absorption properties and probing morphology and
      crystal structure. These undertakings reveal that H(2)O exposure does not simply
      cause CH(3)NH(3)PbI(3) to revert to PbI(2). It is shown that, in the dark, H(2)O
      is able to complex with the perovskite, forming a hydrate product similar to
      (CH(3)NH(3))(4)PbI(6).2H(2)O. This causes a decrease in absorption across the
      visible region of the spectrum and a distinct change in the crystal structure of
      the material. Femtosecond transient absorption spectroscopic measurements show
      the effect that humidity has on the ultrafast excited state dynamics of
      CH(3)NH(3)PbI(3). More importantly, the deleterious effects of humidity on
      complete solar cells, specifically on photovoltaic efficiency and stability, are
      explored in the light of these spectroscopic understandings.

PMID- 25590695
TI  - PTSD-related paradoxical insomnia: an actigraphic study among veterans with
      chronic PTSD.
AB  - BACKGROUND: Sleep disturbance is a common self-reported complaint by PTSD
      patients. However, there are controversies in documenting objective indices of
      disrupted sleep in these patients. The aim of the present study was to assess
      sleep disturbances in veterans with chronic PTSD, using both subjective and
      objective assessments. METHODS: Thirty two PTSD patients with complaints of
      insomnia were evaluated using the Clinician Administrated PTSD Scale version 1
      (CAPS) and completed the Pittsburg Sleep Quality Index (PSQI) for subjective
      evaluation of their sleep. For objective evaluation, participants underwent two
      consecutive overnight actigraphic assessments. Total Sleep Time (TST), Sleep
      Latency (SL), Sleep Efficiency (SE) and Number of Awakening (NWAK) were measured
      in all participants. RESULTS: Participants underestimated TST (p less than
      0.0001), SE (p less than 0.0001) as well as NASO (0.03) in the questionnaire
      compared to the actigraphic assessment and overestimated SL (p less than 0.0001).
      CONCLUSIONS: Objective sleep parameters do not adversely affect veterans with
      chronic PTSD. Self-reported sleep disturbance in these patients is not reliable
      and objective sleep assessments are necessary.

PMID- 25590696
TI  - Bio-inspired multiproperty materials: strong, self-healing, and transparent
      artificial wood nanostructures.
AB  - Nanocomposite films possessing multiple interesting properties (mechanical
      strength, optical transparency, self-healing, and partial biodegradability) are
      discussed. We used Layer-by-Layer assembly to prepare micron thick wood-inspired
      films from anionic nanofibrillated cellulose and cationic poly(vinyl amine). The
      film growth was carried out at different pH values to obtain films of different
      chemical composition, whereby, and as expected, higher pH values led to a higher
      polycation content and also to 6 times higher film growth increments (from 9 to
      55 nm per layer pair). In the pH range from 8 to 11, micron thick and optically
      transparent LbL films are obtained by automated dipping when dried regularly in a
      stream of air. Films with a size of 10 cm(2) or more can be peeled from flat
      surfaces; they show tensile strengths up to about 250 MPa and Young's moduli up
      to about 18 GPa as controlled by the polycation/polyanion ratio of the film.
      Experiments at different humidities revealed the plasticizing effect of water in
      the films and allowed reversible switching of their mechanical properties.
      Whereas dry films are strong and brittle (Young's modulus: 16 GPa, strain at
      break: 1.7%), wet films are soft and ductile (Young's modulus: 0.1 GPa, strain at
      break: 49%). Wet film surfaces even amalgamate upon contact to yield mechanically
      stable junctions. We attribute the switchability of the mechanical properties and
      the propensity for self-repair to changes in the polycation mobility that are
      brought about by the plastifying effect of water. 

PMID- 25590698
TI  - New information on molecular features of the dengue virus type 3, panorama of the
      amphibian research in Brazil, and a new extinct Cretaceous angiosperm.

PMID- 25590697
TI  - Graphene oxide as efficient high-concentration formaldehyde scavenger and
      reutilization in supercapacitor.
AB  - Graphene oxide (GO) was investigated as a low-cost and high-efficient scavenger
      for high-concentration formaldehyde in alkali media. It showed very high removal
      capacity, 411 mg of formaldehyde per milligram of GO, and strong resistant to
      temperature changes. Additionally, the used GO can be easily renewed by a simple
      electrochemical method. By analyzing the componential and electrochemical
      characterizations of GO before and after use, the results showed that the
      degradation mechanism of formaldehyde is a collaborative process of chemical
      oxidation and physical adsorption, and the former dominates the degradation
      process. With the aid of oxygen-containing groups in GO, most formaldehyde can be
      easily oxidized by GO in alkaline media (this is equivalent to GO was reduced by
      formaldehyde). On the other hand, the used GO (reduced GO, noted as rGO) exhibits
      more ideal electronic double-layer capacitor (EDLC) feature than GO, along with
      higher rate capacitance (up to 136 F g(-1) at 50 A g(-1)). In short, GO is not
      only an efficient formaldehyde scavenger, but the used GO (rGO) can serve as
      promising electrical energy storage material. This study provides new insights
      for us to reutilize the discarded adsorbents generated from the environmental
      protection.

PMID- 25590699
TI  - Evaluation of the use of Leptodactylus ocellatus (Anura: Leptodactylidae) frog
      tissues as bioindicator of metal contamination in Contas River, Northeastern
      Brazil.
AB  - This paper presents a study on the viability of the use of tissues of the
      Leptodactylus ocellatus species (Anura Leptodactylidae) as a bioindicator of
      metal pollution. The study is based on the determination and correlation of the
      concentrations of manganese, chromium, zinc, nickel, copper and iron in sediments
      and tissues (skin, muscles and viscera) of the frog Leptodactylus ocellatus
      collected in the middle region of the Contas River in Bahia, Brazil. The highest
      levels of the metals studied were found in the viscera of this animal. In this
      tissue, a higher correlation of the concentration of these metals with those
      found in sediments was also observed. The concentrations of elements found in the
      skin and muscles of these amphibians have revealed no correlation with the
      sediment where they were collected. According to the results obtained, the
      viscera of the L. ocellatus species presents itself as a good bioindicator of
      contamination by the metals studied. 

PMID- 25590700
TI  - Complete assignments of NMR data and assessment of trypanocidal activity of new
      eremantholide C derivatives.
AB  - Chemical transformations of eremantholide C (1), a sesquiterpene lactone that was
      isolated from Lychnophora trichocarpha Spreng. led to five new derivatives: 1',2'
      epoxyeremantholide C (2), 5-n-propylamine-4,5-dihydro-1',2'-epoxyeremantholide C
      (3), 5-n-propylammonium-4,5-dihydro-1',2'-epoxyeremantholide C chloride (4), 5-n
      propylammonium-4,5-dihydroeremantolide C chloride (5) and 16-O-ethyleremantholide
      C (6). The structures of all these derivatives were assigned on the basis of IR,
      MS, 1H and 13C NMR data by 1D and 2D techniques. Eremantholide C and the
      derivatives 2, 4 and 5 were evaluated against trypomastigotes Y and CL strains of
      Trypanosoma cruzi. Eremantholide C completely inhibited the growth of both the
      parasites strains while all derivatives were partially active against the CL
      strain and inactive against the Y strain.

PMID- 25590702
TI  - Coastline changes and sedimentation related with the opening of an artificial
      channel: the Valo Grande Delta, SE Brazil.
AB  - The role played by human activity in coastline changes indicates a general
      tendency of retreating coasts, especially deltaic environments, as a result of
      the recent trend of sea level rise as well as the blockage of the transfer of
      sediments towards the coast, especially due to the construction of dams. This is
      particularly important in deltaic environments which have been suffering a
      dramatic loss of area in the last decades. In contrast, in this paper, we report
      the origin and evolution of an anthropogenic delta, the Valo Grande delta, on the
      south-eastern Brazilian coast, whose origin is related to the opening of an
      artificial channel and the diversion of the main flow of the Ribeira de Iguape
      River. The methodology included the analysis of coastline changes, bathymetry and
      coring, which were used to determine the sedimentation rates and grain-size
      changes over time. The results allowed us to recognize the different facies of
      the anthropogenic delta and establish its lateral and vertical depositional
      trends. Despite not being very frequent, anthropogenic deltas represent a
      favorable environment for the record of natural and anthropogenic changes in
      historical times and, thus, deserve more attention from researchers of different
      subjects. 

PMID- 25590701
TI  - The sea-level highstand correlated to marine isotope stage (MIS) 7 in the coastal
      plain of the state of Rio Grande do Sul, Brazil.
AB  - The coastal plain of the state of Rio Grande do Sul, in southern Brazil, includes
      four barrier-lagoon depositional systems formed by successive Quaternary sea
      level highstands that were correlated to marine isotope stages (MIS) 11, 9, 5 and
      1, despite the scarcity of absolute ages. This study describes a sea-level
      highstand older than MIS 5, based on the stratigraphy, ages and fossils of the
      shallow marine facies found in coastal barrier (Barrier II). This facies outcrops
      along the banks of Chui Creek, it is composed of fine, well-sorted quartz sand
      and contains ichnofossils Ophiomorpha nodosa and Rosselia sp., and molluscan
      shells. The sedimentary record indicates coastal aggradation followed by sea
      level fall and progradation of the coastline. Thermoluminescence (TL) and
      electron spin resonance (ESR) ages from sediments and fossil shells point to an
      age of ~220 ka for the end of this marine transgression, thus correlating it to
      MIS 7 (substage 7e). Altimetric data point to a maximum amplitude of about 10
      meters above present-day mean sea-level, but tectonic processes may be involved.
      Paleoceanographic conditions at the time of the highstand and correlations with
      other deposits in the Brazilian coasts are also discussed.

PMID- 25590703
TI  - An experimental study of the partitioning of trace elements between rutile and
      silicate melt as a function of oxygen fugacity.
AB  - Subduction zone or arc magmas are known to display a characteristic depletion of
      High Field Strength Elements (HFSE) relative to other similarly incompatible
      elements, which can be attributed to the presence of the accessory mineral rutile
      (TiO2) in the residual slab. Here we show that the partitioning behavior of
      vanadium between rutile and silicate melt varies from incompatible (~0.1) to
      compatible (~18) as a function of oxygen fugacity. We also confirm that the HFSE
      are compatible in rutile, with D(Ta)> D(Nb)>> (D(Hf)>/~ D(Zr), but that the level
      of compatibility is strongly dependent on melt composition, with partition
      coefficients increasing about one order of magnitude with increasing melt
      polymerization (or decreasing basicity). Our partitioning results also indicate
      that residual rutile may fractionate U from Th due to the contrasting (over 2
      orders of magnitude) partitioning between these two elements. We confirm that, in
      addition to the HFSE, Cr, Cu, Zn and W are compatible in rutile at all oxygen
      fugacity conditions. 

PMID- 25590704
TI  - Seismogenic faulting in the Meruoca granite, NE Brazil, consistent with a local
      weak fracture zone.
AB  - A sequence of earthquakes occurred in 2008 in the Meruoca granitic pluton,
      located in the northwestern part of the Borborema Province, NE Brazil. A
      seismological study defined the seismic activity occurring along the seismically
      defined Riacho Fundo fault, a 081 degrees  striking, 8 km deep structure. The
      objective of this study was to analyze the correlation between this seismic
      activity and geological structures in the Meruoca granite. We carried out
      geological mapping in the epicentral area, analyzed the mineralogy of fault
      rocks, and compared the seismically-defined Riacho Fundo fault with geological
      data. We concluded that the seismically-defined fault coincides with ~E-W
      striking faults observed at outcrop scale and a swarm of Mesozoic basalt dikes.
      We propose that seismicity reactivated brittle structures in the Meruoca granite.
      Our study highlights the importance of geological mapping and mineralogical
      analysis in order to establish the relationships between geological structures
      and seismicity at a given area.

PMID- 25590705
TI  - Late Pleistocene carnivores (Carnivora: Mammalia) from a cave sedimentary deposit
      in northern Brazil.
AB  - The Brazilian Quaternary terrestrial Carnivora are represented by the following
      families: Canidae, Felidae, Ursidae, Procyonidae Mephitidae and Mustelidae. Their
      recent evolutionary history in South America is associated with the uplift of the
      Panamanian Isthmus, and which enabled the Great American Biotic Interchange
      (GABI). Here we present new fossil records of Carnivora found in a cave in Aurora
      do Tocantins, Tocantins, northern Brazil. A stratigraphical controlled collection
      in the sedimentary deposit of the studied cave revealed a fossiliferous level
      where the following Carnivora taxa were present: Panthera onca, Leopardus sp.,
      Galictis cuja, Procyon cancrivorus, Nasua nasua and Arctotherium wingei. Dating
      by Electron Spinning Resonance indicates that this assemblage was deposited
      during the Last Glacial Maximum (LGM), at least, 22.000 YBP. The weasel, G. cuja,
      is currently reported much further south than the record presented here. This may
      suggest that the environment around the cave was relatively drier during the LGM,
      with more open vegetation, and more moderate temperatures than the current
      Brazilian Cerrado.

PMID- 25590706
TI  - A new angiosperm from the Crato Formation (Araripe Basin, Brazil) and comments on
      the Early Cretaceous monocotyledons.
AB  - The Crato Formation paleoflora is one of the few equatorial floras of the Early
      Cretaceous. It is diverse, with many angiosperms, especially representatives of
      the clades magnoliids, monocotyledons and eudicots, which confirms the assumption
      that angiosperm diversity during the last part of the Early Cretaceous was
      reasonably high. The morphology of a new fossil monocot is studied and compared
      to all other Smilacaceae genus, especially in the venation. Cratosmilax jacksoni
      gen. et sp. nov. can be related to the Smilacaceae family, becoming the oldest
      record of the family so far. Cratosmilax jacksoni is a single mesophilic leaf
      with entire margins, ovate shape, with acute apex and base, four venation orders
      and main acrodromous veins. It is the first terrestrial monocot described for the
      Crato Formation, monocots were previously described for the same formation, and
      are considered aquatics. Cratosmilax jacksoni is the first fossil record of
      Smilacaceae in Brazil, and the oldest record of this family. 

PMID- 25590707
TI  - A new prozostrodontian cynodont (Therapsida) from the Late Triassic Riograndia
      Assemblage Zone (Santa Maria Supersequence) of Southern Brazil.
AB  - We report here on a new prozostrodontian cynodont, Botucaraitherium belarminoi
      gen. et sp. nov., from the Late Triassic Riograndia Assemblage Zone (AZ) of the
      Candelaria Sequence (Santa Maria Supersequence), collected in the Botucarai Hill
      Site, Candelaria Municipality, state of Rio Grande do Sul, Brazil. The new taxon
      is based on a single specimen (holotype MMACR-PV-003-T) which includes the left
      lower jaw, without postdentary bones, bearing the root of the last incisor,
      canine and four postcanines plus one partial crown inside the dentary, not
      erupted, and two maxillary fragments, one with a broken canine and another with
      one postcanine. The features of the lower jaw and lower/upper postcanines
      resemble those of the prozostrodontians Prozostrodon brasiliensis from the older
      Hyperodapedon AZ and Brasilodon quadrangularis and Brasilitherium riograndensis
      from the same Riograndia AZ. The inclusion of Botucaraitherium within a broad
      phylogenetic analysis, positioned it as a more derived taxon than tritylodontids,
      being the sister-taxon of Brasilodon, Brasilitherium plus Mammaliaformes.
      Although the new taxon is based on few cranial elements, it represents a
      additional faunal component of the Triassic Riograndia AZ of southern Brazil, in
      which small-sized derived non-mammaliaform cynodonts, closely related to the
      origin of mammaliaforms, were ecologically well succeed and taxonomically
      diverse.

PMID- 25590708
TI  - Reproductive phenology and sharing of floral resource among hummingbirds
      (Trochilidae) in inflorescences of Dahlstedtia pinnata (Benth.) Malme. (Fabaceae)
      in the Atlantic forest.
AB  - The purpose of this study was to investigate the reproductive phenology and
      sharing of floral resource (nectar) of Dahlstedtia pinnata (Benth.) Malme.
      (Fabaceae), endemic of Atlantic forest, among hummingbirds. For the phenology, we
      looked at the presence of reproductive structures in the plants, and for floral
      resource sharing, the frequency of potential pollinators and foraging behaviors
      were examined. This study was conducted in Pedra Branca State Park, in state of
      Rio de Janeiro, in a dense ombrophilous forest, between August 2010 and August
      2011. Flowering occurred between December 2010 and March 2011, and fruiting
      between April and June 2011. Hummingbirds' foraging schedules differed
      significantly, with legitimate visits to the flowers occurring in the morning and
      illegitimate visits occurring during late morning and the afternoon. Five species
      visited flowers, three of which were legitimate visitors: Phaethornis ruber, P.
      pretrei, and Ramphodon naevius. Amazilia fimbriata and Thalurania glaucopis
      females only visited illegitimately. Phaethornis ruber robbed nectar (78% of
      illegitimate visits, n=337). Ramphodon naevius, with a territorial foraging
      behavior and a body size bigger than that of other observed hummingbird species,
      dominated the floral visits, which suggests that D. pinnata is an important
      nourishing resource for this endemic bird of the Atlantic forest, currently
      globally categorized as Near Threatened. 

PMID- 25590709
TI  - Gene homozygosis and mitotic recombination induced by camptothecin and irinotecan
      in Aspergillus nidulans diploid cells.
AB  - Mitotic recombination is a process involved in carcinogenesis which can lead to
      genetic loss through the loss of heterozygosity. The recombinogenic potentials of
      two anticancer drugs topoisomerase I inhibitors, camptothecin (CPT) and
      irinotecan (CPT-11), were evaluated in the present study. The homozygotization
      assay, which assess the induction of mitotic recombination and gene homozygosis,
      as well as the heterozygous A757//UT448 diploid strain of Aspergillus nidulans
      were employed. The three non-cytotoxic concentrations of CPT (3.5 ng mL-1, 10.5
      ng mL-1 and 17.4 ng mL-1) were found to induce both mitotic recombination and
      gene homozygosis. CPT treatment produced three diploids homozygous, for
      nutritional and conidia color genes, and Homozygotization Indices (HI)
      significantly different from negative control. On the other hand, only the
      highest CPT-11 concentration tested (18 ug mL-1), corresponding to the maximal
      single chemotherapeutic dose, produced HI values higher than 2.0 and
      significantly different from negative control HI values. The recombinogenic
      effects of both topoisomerase I blockers were associated with the recombinational
      repair of DNA strand breaks induced by CPT and CPT-11. The anticancer drugs CPT
      and CPT-11 may be characterized as secondary malignancies promoters in cancer
      patients after chemotherapy treatment. 

PMID- 25590710
TI  - Richness and abundance of the cardini group of Drosophila (Diptera,
      Drosophilidae) in the Caatinga and Atlantic Forest biomes in northeastern Brazil.
AB  - Brazil has a high diversity of flies of the genus Drosophila, and part of this
      richness is represented by the cardini group. We analyzed the fluctuations in the
      richness and abundance of this group, in environments that had never previously
      been studied in the northeastern region of Brazil. Among the 28,204 drosophilids
      sampled, 1,294 belonged to the cardini group and were represented by D.
      polymorpha, D. cardini, D. neocardini and D. cardinoides. Occurrences of D.
      neocardini and D. cardinoides were registered for the first time in the Caatinga.
      In this biome, D. cardini stood out as having the highest abundance, and D.
      polymorpha was not observed. In the coastal Atlantic Forest, D. cardini was not
      registered, but D. polymorpha was found in all the localities investigated.
      Mangrove swamps were the environment with the lowest abundance and richness of
      the cardini group. The High-altitude Forest presented the highest richness of
      this group. We suggest that the high abundance of D. polymorpha in the High
      altitude Forest and in the coastal Atlantic Forest may be a reflection of the
      historical relationship between these two environments. 

PMID- 25590711
TI  - Copepod distribution and production in a Mid-Atlantic Ridge archipelago.
AB  - The Saint Peter and Saint Paul Archipelago (SPSPA) are located close to the
      Equator in the Atlantic Ocean. The aim of this study was to assess the spatial
      variations in the copepod community abundance, and the biomass and production
      patterns of the three most abundant calanoid species in the SPSPA. Plankton
      samples were collected with a 300 um mesh size net along four transects (north,
      east, south and west of the SPSPA), with four stations plotted in each transect.
      All transects exhibited a tendency toward a decrease in copepod density with
      increasing distance from the SPSPA, statistically proved in the North. Density
      varied from 3.33 to 182.18 ind.m-3, and differences were also found between the
      first perimeter (first circular distance band) and the others. The total biomass
      varied from 15.25 to 524.50 10-3 mg C m-3 and production from 1.19 to 22.04 10-3
      mg C m-3d-1. The biomass and production of Undinula vulgaris (Dana, 1849),
      Acrocalanus longicornis Giesbrecht, 1888 and Calocalanus pavo (Dana, 1849) showed
      differences between some transects. A trend of declining biodiversity and
      production with increasing distance from archipelago was observed, suggesting
      that even small features like the SPSPA can affect the copepod community in
      tropical oligotrophic oceanic areas. 

PMID- 25590712
TI  - Effect of land use on mayfly assemblages structure in Neotropical headwater
      streams.
AB  - The aim of this study was to test the effect of agricultural and forestry land
      use on the structure of mayfly assemblages in low-order streams. Twenty-nine
      headwater streams were investigated in the state of Sao Paulo. We analyzed 15
      streams in pristine areas (mixed tropical rainforest, semideciduous forest and
      dense tropical rainforest), and 14 streams covered with sugarcane, eucalyptus and
      pasture. Mayfly richness obtained by rarefaction curves was higher in pristine
      areas (21 genera), especially in mixed and semideciduous forest when compared to
      land use (9 genera), where values were particularly low in sugarcane plantation
      (3 genera). The non-metric multidimensional scaling (NMDS) ordination showed
      clear difference in mayfly assemblages between land uses and pristine areas,
      supported by analysis of similarity (R=0.67, p=0.001). In partial redundancy
      analysis (pRDA), the environmental descriptors that best explained differences in
      assemblage structure were Riparian, Channel and Environmental Inventory (RCE)
      index score, percentage of fine sediment stream substrate, water pH and land
      elevation. Our results show that agricultural and forestry land use has a strong
      negative effect on the structure of mayfly assemblages. These results also
      support the use of mayflies as environmental indicators, as some genera were
      sensitive to changes in land use, while others responded to naturally occurring
      changes in the study area.

PMID- 25590713
TI  - A two-plasmid strategy for engineering a dengue virus type 3 infectious clone
      from primary Brazilian isolate.
AB  - Dengue infections represent one of the most prevalent arthropod-borne diseases
      worldwide, causing a wide spectrum of clinical outcomes. Engineered infectious
      clone is an important tool to study Dengue virus (DENV) biology. Functional full
      length cDNA clones have been constructed for many positive-strand RNA viruses and
      have provided valuable tools for studying the molecular mechanisms involved in
      viral genome replication, virion assembly, virus pathogenesis and vaccine
      development. We report herein the successful development of an infectious clone
      from a primary Brazilian isolate of dengue virus 3 (DENV3) of the genotype III.
      Using a two-plasmid strategy, DENV3 genome was divided in two parts and cloned
      separately into a yeast-bacteria shuttle vector. All plasmids were assembled in
      yeast by homologous recombination technique and a full-length template for
      transcription was obtained by in vitro ligation of the two parts of the genome.
      Transcript-derived DENV3 is infectious upon transfection into BHK-21 cells and in
      vitro characterization confirmed its identity. Growth kinetics of transcript
      derived DENV3 was indistinguishable from wild type DENV3. This system is a
      powerful tool that will help shed light on molecular features of DENV biology, as
      the relationship of specific mutations and DENV pathogenesis. 

PMID- 25590714
TI  - Pequi leaves incorporated into the soil reduce the initial growth of cultivated,
      invasive and native species.
AB  - Studies have identified the phytotoxicity of many native species of the Cerrado;
      however, most of them were conducted either in inert substrates, or using
      exaggerate proportions of plant material. We investigated the phytotoxicity of
      pequi leaves added to substrate soil in quantities compatible with the litter
      produced by this species. Pequi leaves were triturated and added to red latosol
      in concentrations of 0.75%, 1.5% and 3%; the control was constituted of leafless
      soil. These mixtures were added to pots and irrigated daily to keep them moist.
      Germinated seeds of the cultivated sorghum and sesame, of the invasive brachiaria
      and of the native purple ipe, were disposed in the pots to grow for five to seven
      days at 30 degrees C within a photoperiod of 12 h. Seedlings of all the species
      presented a reduction in their initial growth in a dose-dependent way. In
      general, the root growth was more affected by the treatments than the shoot
      growth; moreover, signs of necrosis were observed in the roots of the sorghum,
      sesame and brachiaria. The phytotoxic effects generated by relatively small
      quantities of leaves, in a reasonable range of species within a soil substrate,
      suggest potential allelopathy of pequi leaves under natural conditions.

PMID- 25590715
TI  - The population structure of two sympatric hermit-crab species on a subtidal rocky
      shore of an island in southeastern Brazil.
AB  - The main goal of this investigation was to characterize the population structure
      and shell occupancy of two sympatric hermit-crab species, Pagurus brevidactylus
      and Paguristes tortugae. The study was undertaken at Couves Island on the
      southeastern coast of Brazil, from March 2010 through February 2011, on subtidal
      rocky bottoms. Specimens were collected by SCUBA diving sessions. A total of 195
      individuals of P. brevidactylus and 132 of P. tortugae were examined. Both
      populations showed unimodal size-frequency distributions, which were non-normal
      for P. brevidactylus and normal for P. tortugae. The median size of P.
      brevidactylus was significantly smaller than P. tortugae; in both species, males
      were significantly larger than females. For both, juveniles and ovigerous females
      were recorded in all size classes and in almost the entire sampling period. No
      significant departures from the 1:1 sex ratio were detected, although some size
      classes were skewed. Overlaps in shell occupation were recorded. Pagurus
      brevidactylus and P. tortugae showed similar population features; they reached
      sexual maturity at small sizes, and the nearly year-round presence of young and
      ovigerous females suggests continuous reproduction. These inter-specific
      interactions involving resource partitioning suggest a regulatory process that is
      probably part of the equilibrium strategy of these populations.

PMID- 25590716
TI  - Composition of functional ecological guilds of the fish fauna of the internal
      sector of the Amazon Estuary, Para, Brazil.
AB  - The present study describes the spatial and temporal structure of the estuarine
      fish community in the internal sector of the Amazon Estuary. Samples were
      obtained in the main channels and tidal creeks of Guajara and Marajo Bays and
      Guama River. A total of 41,516 fish specimens were collected, representing 136
      taxa, 38 families and 12 orders. In the dry season, the mean salinity of the main
      channel increased along a limnic-marine gradient, between the Guama River and the
      Marajo Bay. Species richness was lowest in the mouth of the Guama River and in
      the right margin of the Guajara Bay. Fish species composition and environmental
      guilds differed markedly among areas: Migrants and Freshwater Stragglers were
      dominant in the Guama River and the Guajara Bay, while Estuarine, Marine
      Stragglers and Migrants predominated in the Marajo Bay. However, the trophic
      guilds were still relatively well balanced, in functional terms. Piscivores and
      Zoobenthivores were the dominant feeding functional groups in all the studied
      areas. In this study, the assessment of the community and the use of the guild
      approach were efficient to describe the structure and functioning of the
      assemblages of estuarine fish also helping to assess the anthropogenic pressures
      in the area.

PMID- 25590717
TI  - Preferential accumulation of sex and Bs chromosomes in biarmed karyotypes by
      meiotic drive and rates of chromosomal changes in fishes.
AB  - Mechanisms of accumulation based on typical centromeric drive or of chromosomes
      carrying pericentric inversions are adjusted to the general karyotype
      differentiation in the principal Actinopterygii orders. Here, we show that
      meiotic drive in fish is also supported by preferential establishment of sex
      chromosome systems and B chromosomes in orders with predominantly bi-brachial
      chromosomes. The mosaic of trends acting at an infra-familiar level in fish could
      be explained as the interaction of the directional process of meiotic drive as
      background, modulated on a smaller scale by adaptive factors or specific
      karyotypic properties of each group, as proposed for the orthoselection model. 

PMID- 25590718
TI  - Antibiotic resistance and enterotoxin genes in Staphylococcus sp. isolates from
      polluted water in Southern Brazil.
AB  - The aim of this study was to evaluate the species distribution, antibiotic
      resistance profile and presence of enterotoxin (SE) genes in staphylococci
      isolated from the Diluvio stream in South Brazil. Eighty-eight staphylococci were
      identified, 93.18% were identified as coagulase-negative (CNS) and 6.82%
      coagulase-positive (CPS). Fourteen Staphylococcus species were detected and the
      most frequently were Staphylococcus cohnii (30.48%) and S. haemolyticus (21.95%).
      Resistance to erythromycin was verified in 37.50% of the strains, followed by
      27.27% to penicillin, 12.50% to clindamycin, 6.81% to trimethoprim
      sulfamethoxazole, 5.68% to chloramphenicol and 2.27% to norfloxacin. None of the
      investigated strains showed gentamicin and ciprofloxacin resistance. The strains
      were tested for the presence of sea, seb, sec, sed and see genes by PCR and only
      CNS strains (43.18%) showed positive results to one or more SE genes. The
      scientific importance of our results is due to the lack of data about these
      topics in polluted waters in Brazil. In conclusion, polluted waters from the
      Diluvio stream may constitute a reservoir for disseminating antibiotic-resistance
      and enterotoxin into the community. In addition, the detection of staphylococci
      in the polluted waters of the Diluvio stream indicated a situation of
      environmental contamination and poor sanitation conditions. 

PMID- 25590719
TI  - Attenuation of oxidative stress, inflammation and apoptosis by ethanolic and
      aqueous extracts of Crocus sativus L. stigma after chronic constriction injury of
      rats.
AB  - In our previous study, the ethanolic and aqueous extracts of Crocus sativus
      elicited antinociceptive effects in the chronic constriction injury (CCI) model
      of neuropathic pain. In this study, we explored anti-inflammatory, anti-oxidant
      and anti-apoptotic effects of such extracts in CCI animals. A total of 72 animals
      were divided as vehicle-treated CCI rats, sham group, CCI animals treated with
      the effective dose of aqueous and ethanolic extracts (200 mg/kg, i.p.). The
      lumbar spinal cord levels of proinflammatory cytokines including tumor necrosis
      factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin 6 (IL-6),
      were evaluated at days 3 and 7 after CCI (n=3, for each group). The apoptotic
      protein changes were evaluated at days 3 and 7 by western blotting. Oxidative
      stress markers including malondialdehyde (MDA) and glutathione reduced (GSH),
      were measured on day 7 after CCI. Inflammatory cytokines levels increased in CCI
      animals on days 3 and 7, which were suppressed by both extracts. The ratio of
      Bax/ Bcl2 was elevated on day 3 but not on day 7, in CCI animals as compared to
      sham operated animals and decreased following treatment with both extracts at
      this time. Both extracts attenuated MDA and increased GSH levels in CCI animals.
      It may be concluded that saffron alleviates neuropathic pain, at least in part,
      through attenuation of proinflammatory cytokines, antioxidant activity and
      apoptotic pathways. 

PMID- 25590720
TI  - Food restriction beginning at lactation interferes with the cellular dynamics of
      the mucosa and colonic myenteric innervation in adult rats.
AB  - The effects of food restriction (FR) on the morphoquantitative aspects of the
      wall and myenteric neurons of the proximal colon in adult rats were analysed. FR
      was imposed by duplication of the experimental brood size in relation to the
      control brood during lactation. The FR group received a 50% reduction of food
      from weaning until 90 days of age. Samples of the colon underwent histological
      processing to morphometrically analyze the crypts, muscularis mucosae, tunica
      mucosa, and muscularis externa. We determined the number of goblet cells and
      serotoninergic enteroendocrine cells, and morphoquantitatively studied the
      myenteric neuronal population. FR caused hypertrophy in the tunica mucosa,
      increase in crypt depth and in the muscular layer of the mucosa, a decrease in
      the thickness of the tunica muscularis and in the number of goblet cells and an
      increase in serotoninergic cells. A higher neuronal density in the ganglia and a
      reduction of the cell profile area were observed in the FR group. FR imposed
      since lactation led to hypertrophy of the tunica mucosa, a reduction of neutral
      mucin production, atrophy of the tunica muscularis, and an increase in the
      survival neuronal in adult rats, attributable to an increase in the number of
      serotoninergic enteroendocrine cells in mucosa. 

PMID- 25590721
TI  - Karyotype characterization and nuclear DNA content measurement in Bromeliaceae:
      state of the art and future perspectives.
AB  - In Bromeliaceae, cytogenetic and flow cytometry analyses have been performed to
      clarify systematic and evolutionary aspects. Karyotyping approaches have shown
      the relatively high chromosome number, similar morphology and small size of the
      chromosomes. These facts have prevented a correct chromosome counting and
      characterization. Authors have established a basic chromosome number of x = 25
      for Bromeliaceae. Recently, one karyomorphological analysis revealed that x = 25
      is no longer the basic chromosome number, whose genome may have a polyploid
      origin. Besides cytogenetic characterization, the 2C DNA content of bromeliads
      has been measured. Nuclear DNA content has varied from 2C = 0.60 to 2C = 3.34
      picograms. Thus, in relation to most angiosperms, the 2C DNA content of
      Bromeliaceae species as well as their chromosome size can be considered
      relatively small. In spite of some advances, cytogenetic and flow cytometry data
      are extremely scarce in this group. In this context, this review reports the
      state of the art in karyotype characterization and nuclear DNA content
      measurement in Bromeliaceae, emphasizing the main problems and suggesting
      prospective solutions and ideas for future research. 

PMID- 25590722
TI  - Seasonal changes of water quality in a tropical shallow and eutrophic reservoir
      in the metropolitan region of Recife (Pernambuco-Brazil).
AB  - This study investigated the water quality in an urban eutrophic reservoir in
      Northeastern Brazil, considering the influence of seasonality. Monthly, samples
      were collected in the sub-surface reservoir. The following abiotic variables were
      analyzed: temperature, pH, dissolved oxygen, apparent color, turbidity,
      conductivity, fluoride, total nitrogen, chlorides, total dissolved solids, total
      hardness, iron, copper, manganese, aluminum, chlorophyll-a and phaeophytin. Total
      and thermotolerant coliforms were analyzed according to APHA (2012).
      Cyanobacteria density was quantified through its biomass. The data were analyzed
      using one- way ANOVA and Pearson correlation test. Higher values mean
      phytoplankton biomass (26.3mm3.L-1) occurred in the dry season, especially
      Planktothrix agardhii and Geiterinema amphibium, which occurred in 100% of
      samples. High trophic state index was detected throughout the year. Seasonality
      exerted some influence on both biotic and abiotc variables, leading to changes in
      water quality of the reservoir. 

PMID- 25590723
TI  - Diversity patterns, research trends and mismatches of the investigative efforts
      to amphibian conservation in Brazil.
AB  - The number of papers on biology of amphibians has increased in the recent years.
      A detailed overview of the publications on amphibians can be very useful in
      assessing the status of our knowledge about this taxonomic group. Due to the
      large number of articles published, we aimed to assess the scientific
      contribution of herpetological researches carried out between the years 2001 and
      2010 on Brazilian amphibians, considering the diversity patterns, the threats and
      the research topics that have been published most often. We applied scientometric
      attention indexes in the reviewed studies from seven scientific databases. To
      examine the relationship between the numbers of species recorded locally and
      regionally at different spatial scales, we used an additive partitioning of
      diversity in three hierarchical levels (i.e., states, geographic regions and
      biomes). We evaluated 892 articles and 914 species, which showed that 65 % of the
      total diversity of Brazilian amphibian species was represented by the beta
      diversity among the biomes. We identified many differences in the allocation of
      research efforts for taxonomic groups, threats categories, geographic regions,
      and research topics, highlighting the main research trends conducted and the
      priority themes for investigation of further papers on Brazilian amphibians. 

PMID- 25590724
TI  - Chaco ansilta new species from Mendoza province, Western Argentina (Araneae:
      Nemesiidae).
AB  - A new species of Chaco Tullgren, 1905 is described and illustrated from the
      Andean foothills of Mendoza province, western Argentina. This is the tenth
      species of the genus and the first record of Chaco in Mendoza. An updated key is
      presented for all Chaco species. The cladistic analysis based on a previously
      published morphological character matrix resulted in the consensus tree: (C.
      obscura, C. tucumana, C. castanea, (C. socos + C. tigre) (C. tecka (C. sanjuanina
      (C. Patagonia + C. ansilta sp. nov.)))).

PMID- 25590725
TI  - Effects of atmospheric pollutants on somatic and germ cells of Tradescantia
      pallida (Rose) D.R. Hunt cv. purpurea.
AB  - Anatomical alterations in leaves and DNA damage in cells caused by the
      accumulation of atmospheric pollutants can be measured by epidermal leaf analyses
      and Tradescantia micronuclei assay with early pollen tetrad cells. The present
      study examined the feasibility of using somatic and germ cells of Tradescantia
      pallida for biomonitoring purposes in the city of Dourados, state of Mato Grosso
      do Sul (MS), Brazil. Stomatal, micronucleus and epidermal leaf analyses were
      performed, using standard methodologies, on plants growing at three locations
      during six different time periods. Tradescantia micronuclei data were analyzed
      using SAS 9.2 software package and stomatal data were analyzed using SANEST
      software. Analyses of stomatal characteristics and micronuclei examination in T.
      pallida were found to be an efficient tool for monitoring atmospheric pollution.
      The micronucleus assay suggested that the number of micronuclei in early pollen
      tetrad cells was related to the intensity of vehicular traffic. Increased number
      of epidermal cells and stomata and increased stomatal density observed at
      locations with greater vehicular traffic are likely physiological responses of
      those plants to the increased gas exchange in highly polluted environments. 

PMID- 25590726
TI  - Biflorin: an o-naphthoquinone of clinical significance.
AB  - Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells
      showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an
      isolated compound taken from the roots of the plant Capraria biflora L.
      (Schrophulariaceae), indigenous of the West Indies and South America, which is
      located in temperate or tropical areas. This compound has shown to be strongly
      active against grampositive and alcohol-acid-resistant bacteria. It has been
      efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8
      and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important
      cytotoxic effects. In this article, information related to the first structural
      characterization studies are presented, as well as the latest reports concerning
      the biological activity of this molecule. 

PMID- 25590727
TI  - Soluble fractalkine in the plasma of fibromyalgia patients.
AB  - Fibromyalgia is a form of non-articular rheumatism in which inflammatory
      cytokines seem to be involved. However, there is still no analytical specific
      diagnostic criterion for this disease. The aim was to examine a possible role of
      fractalkine as a biomarker in fibromyalgia. Plasma levels of soluble fractalkine
      were compared between women diagnosed with fibromyalgia (n=17) and healthy women
      (n=10) as controls. Fractalkine released by monocytes was also evaluated.
      Fibromyalgia patients showed lower plasma fractalkine than healthy women. Since
      most inflammatory pathologies show elevated plasma levels of soluble fractalkine,
      the results may contribute towards a differential diagnosis for fibromyalgia. 

PMID- 25590728
TI  - In vivo and in vitro effects of fructose on rat brain acetylcholinesterase
      activity: an ontogenetic study.
AB  - Increased fructose concentrations are the biochemical hallmark of fructosemia, a
      group of inherited disorders on the metabolic pathway of this sugar. The main
      clinical findings observed in patients affected by fructosemia include
      neurological abnormalities with developmental delay, whose pathophysiology is
      still undefined. In the present work we investigated the in vitro and in vivo
      effects of fructose on acetylcholinesterase (AchE) activity in brain structures
      of developing rats. For the in vitro experiments, fructose was added at
      increasing concentrations to the incubation medium. It was observed that fructose
      provoked an inhibition of acetylcholinesterase activity in cerebral cortex of 30
      day-old-rats, even at low concentrations (0.1 mM). For the in vivo experiments,
      rats were killed 1 h after a single fructose administration (5 umol/g). Control
      group received the same volume of saline solution. We found that AchE activity
      was increased in cerebral cortex of 30- and 60-day-old rats receiving fructose
      administration. Finally, we observed that AchE activity was unaffected by acute
      fructose administration in cerebral cortex, striatum or hippocampus of 15- and 90
      day-old rats. The present data suggest that a disruption in cholinergic
      homeostasis may be involved in the pathophysiology of brain damage observed in
      young patients affected by fructosemia. 

PMID- 25590729
TI  - Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced
      PC12 cells.
AB  - Protein tau plays a pivotal role in the pathophysiology of Alzheimer's disease,
      where its hyperphos-phorylation promotes aggregation and microtubule
      destabilization. Tau undergoes alternative splicing which generates six isoforms
      in the human brain, due to inclusion/exclusion of exons 2, 3 and 10.
      Dysregulation of the splicing process of tau exon 10 is sufficient to cause
      tauopathy and has shown to be influenced by beta-amyloid peptides, but splicing
      of other exons is less studied. We studied the effects of beta-amyloid(42) in the
      alternative splicing of tau exons 2/3 and 6, using untreated and Nerve Growth
      Factor-induced PC12 cells. Beta-amyloid exposure caused formed cell processes to
      retract in differentiated cells and altered the expression of exons 2/3 in both
      undifferentiated and differentiated cells. Expression of exon 6 was repressed in
      undifferentiated cells only. Our results suggest that beta-amyloid interferes
      with the splicing process of exons 2/3, favoring their exclusion and thus the
      expression of immature tau isoforms that are less efficient in stabilizing
      microtubules and may also be more prone to hyperphosphorylation. The molecular
      mechanism for this amyloid-tau interaction remains to be determined, but may have
      potential implications for the understanding of the underlying neuropathological
      processes in Alzheimer's disease. 

PMID- 25590730
TI  - Modulation of diabetes and dyslipidemia in diabetic insulin-resistant rats by
      mangiferin: role of adiponectin and TNF-alpha.
AB  - Mangiferin, present in Mangifera indica bark, was reported to produce
      hypoglycemic and antidiabetic activity in an animal model of genetic type 2
      diabetes and in streptozotocin diabetic rats. Its effect on diabetic insulin
      resistant animals has not been investigated. The current work aimed to explore
      the effect of mangiferin on diabetic insulin-resistant rat model. Diabetes was
      induced by high-fat/high fructose diet for eight weeks followed by a
      subdiabetogenic dose of streptozotocin (HFD-Fr-STZ). Rats were treated with
      mangiferin (20 mg/kg i.p.) for 28 days starting one week after STZ and its
      effects were compared to the standard insulin sensitizer, rosiglitazone. HFD-Fr
      STZ, induced obesity, hyperglycemia and insulin resistance accompanied by
      depletion in liver glycogen and dyslipidemia. Moreover, there was an elevation in
      serum TNF-alpha and a reduction in adiponectin. Mangiferin ameliorated the
      consequences of HFD-Fr-STZ and its actions were comparable to the effects of the
      standard insulin sensitizer, rosiglitazone. The results obtained in this study
      provide evidence that mangiferin is a possible beneficial natural compound for
      type 2 diabetes and metabolic disorders associated with the metabolic syndrome.
      This effect is mediated through improving insulin sensitivity, modulating lipid
      profile and reverting adipokine levels to normal. 

PMID- 25590731
TI  - Differential effect of solution conditions on the conformation of the
      actinoporins Sticholysin II and Equinatoxin II.
AB  - Actinoporins are a family of pore-forming proteins with hemolytic activity. The
      structural basis for such activity appears to depend on their correct folding.
      Such folding encompasses a phosphocholine binding site, a tryptophan-rich region
      and the activity-related N-terminus segment. Additionally, different solution
      conditions are known to be able to influence the pore formation by actinoporins,
      as for Sticholysin II (StnII) and Equinatoxin II (EqtxII). In this context, the
      current work intends to characterize the influence of distinct solution
      conditions in the conformational behavior of these proteins through molecular
      dynamics (MD) simulations. The obtained data offer structural insights into
      actinoporins dynamics in solution, characterizing its conformational behavior at
      the atomic level, in accordance with previous experimental data on StnII and
      EqtxII hemolytic activities. 

PMID- 25590732
TI  - Endothelial, renal and hepatic variables in Wistar rats treated with Vancomycin.
AB  - Vancomycin (VCM) is indicated in combat against Gram-positive infections, but it
      is not considered a first-choice drug because of its adverse effects. It is
      believed that oxidative stress is the primary mechanism of endothelial injury and
      the consequent VCM toxicity, which varies from phlebitis to nephrotoxicity.
      Moreover, dose recommendations, dilution, rates and types of infusion are still
      controversial. The aim of this study was to determine the effect of different VCM
      dilutions in endothelial, liver and kidney injuries by biochemical parameters and
      histopathological analysis. Wistar rats were randomly divided into six groups and
      subjected to femoral vein cannulation for drug administration. Control groups
      received 0.9 ml of saline and the others received VCM (10mg/Kg/day) at dilutions
      of 5.0 and 10.0 mg/mL for 3 and 7 days. Homocysteine, hs-CRP, AST, ALT, GGT,
      urea, creatinine, lycopene, alpha-tocopherol, beta-carotene and retinol were
      analyzed. Kidney, liver and cannulated femoral vein fragments were collected.This
      study showed alterations in ALT which featured hepatotoxicity. However, drug
      dilutions were not able to show changes in other biochemical parameters. In
      contrast, kidney and endothelium pathological changes were observed. More studies
      are needed to characterize VCM induced kidney and endothelium toxicity and
      biochemical markers able to show such morphological modifications. 

PMID- 25590733
TI  - Sublethal effect of concentrations of Metarhizium anisopliae (Metsch.) Sorok on
      the larval stage and immunologic characteristics of Diatraea flavipennella (BOX)
      (Lepidoptera: Crambidae).
AB  - This work aimed to evaluate the effects of Metarhizium anisopliae on Diatraea
      flavipennella and investigate their immune response. Was observed the effect of
      M. anisopliae against larvae of D. flavipennella sprayed at concentrations of
      103, 104, 105 conidia / mL, in which showed differences relative the larval
      period, extending up to 72.0 days in treatment and 25.0 days in the control. The
      results for hemocytes revealed that the most frequent cells when sprayed at the
      concentrations of 103, 105, 107 conidia / mL were the prohemocytes,
      spherulocytes, plasmatocytes and granulocytes in relation to adipohemocytes and
      oenocytoids. The level of nitric oxide was different between the control and the
      concentration 107 spores / mL (24), while the activity of phenoloxidase was
      similar among treatments in 24 and higher concentration 107 spores / mL (60h). In
      biochemical profile of hemocytes was a change in carbohydrates, lipids and
      proteins in response to the fungus. The results indicate that the fungus M.
      anisopliae can be used in the Integrated Management of D. flavipennella by
      presenting pathogenicity and interfere with their development even when exposed
      to small concentrations. 

PMID- 25590734
TI  - Analysis of morpho-agronomic and climatic variables in successive agricultural
      years provides novel information regarding the phenological cycle of Jatropha in
      conditions of the Brazilian cerrado.
AB  - Phenological studies can provide information that enables the understanding of
      the dynamics of plants and how these dynamics are related to the biotic and
      abiotic environment. In order to study the phenological phases of Jatropha during
      two agricultural years, agronomic and climatic variables, such as temperature and
      rainfall, were evaluated. Data for each variable in each year and each genotype
      were subjected to analysis of variance (ANOVA) and the differences were tested at
      5% probability by F test. In addition, the correlation of growth behavior and
      reproductive development of two Jatropha accessions (CNPAE-102 and CNPAE-169) as
      a function of time elapsed after the start of the phenological cycle with
      climatic variables were analyzed through Pearson's correlation. It was found
      that: (i) the resuming of plant growth by producing new branches and flowers of
      both genotypes coincides with the start of the rainy season, (ii) the flowering
      may be related to the increase in temperature and rainfall; (iii) the number of
      inflorescences per plant and number of female flowers determine the number of
      green fruits, (iv) the environmental changes are responsible for the delimitation
      of phenophases; and finally that (v) the responses to phenological changes are
      genotype-dependent. 

PMID- 25590735
TI  - Spatial variability of soil potassium in sugarcane areas subjected to the
      application of vinasse.
AB  - When deposited on land the vinasse can promote improvement in fertility, however,
      often fertilizer application occurs in areas considered homogeneous, without
      taking into account the variability of the soil. The objective of this study was
      to evaluate the effect of vinasse application on potassium content in two classes
      of soils cultivated with sugarcane, and characterize the spatial variability of
      soil using geostatistical techniques. In the 2010 and 2011 crop year, soil
      samples were collected from an experimental grid at 0-0.2 and 0.2-0.4 m depth in
      three soils cultivated with sugarcane, totaling 90 samplings in each grid, for
      the determination of pH, calcium (Ca), magnesium (Mg), potassium (K), phosphorus
      (P), aluminum (Al) and potential acidity (H + Al). The data have been submitted
      to analysis of descriptive statistics and the K attribute was subjected to
      geostatistical analysis. The coefficient of variation indicated medium and high
      variability of K for the three soils. The results showed that the spatial
      dependence of K increased in depth to FRce and decreased to PHlv, indicating that
      the attribute could have followed the pattern of distribution of clay in depth.
      The investigation of the spatial variability of K on the surface and subsurface
      soils provided the definition of management zones with different levels of
      fertility, which can be organized into sub-areas for a more efficient management
      of the resources and the environment. 

PMID- 25590736
TI  - Cotesia flavipes (CAM) (Hymenoptera: Braconidae) supresses immune responses in
      Diatraea flavipennella (BOX) (Lepidoptera: Crambidae).
AB  - The present research aimed to elucidate which aspects of immune responses in
      Diatraea flavipennella are suppressed by the parasitoid Cotesia flavipes, thus,
      ensuring parasitism success. We investigated the presence of apoptosis in fat
      body cells through the TUNEL technique. According to the results, reduced levels
      of nitric oxide and phenoloxidase activity were observed in larvae parasitized
      for three days, and reduced total number of hemocytes, after three and seven
      days. An increase in plasmatocytes and decrease in spherulocytes numbers were
      observed in the differential count on the third day of parasitism. The number of
      melanized microspheres in parasitized larvae was low and indicated less intense
      melanization. The ultrastructural analysis confirmed the immunosuppressive effect
      of C. flavipes on the encapsulation response of D. flavipennella because only the
      formation of hemocytes capsules, adhered to the microspheres' surface, was
      evidenced in non-parasitized caterpillars. The effect of parasitism was also
      recorded on the third day with the presence of hemocytes and apoptosis in fat
      body cells, including aspects of degeneration in the latter. We concluded that C.
      flavipes suppresses cellular and humoral immunological responses in D.
      flavipennella and drastically affects the host's fat tissue.

PMID- 25590737
TI  - Mapping of sites in forest stands.
AB  - Generally, the forest companies use the total one year planting area as a minimum
      stratum of the total population and, consequently, the forest inventory
      processing has been conducted by applying the stratified random sampling to it.
      This study was carried out in the National Forest of Tres Barras, Brazil, and it
      aimed to classify and map the sites of Pinus elliottii stands. A systematic
      sampling was structured into clusters and applied independently by compartments.
      The clusters, in maltese cross, were composed of four sampling subunits, using
      Prodan sampling method with a fixed number of six trees. By analysis of the
      methodology it was possible to confirm the hypothesis: a) the selective thinning
      cause expressive increase of volumetric variability within compartments; b) the
      variation of sites within the compartments causes volumetric expansion of
      variance and this grows proportionally to the quality of the sites; c) the
      stratification in sites results in minimum variance within them; d) the
      stratification in sites resulted in until to 91% reduction of variances within
      them.

PMID- 25590738
TI  - Photosynthetic metabolism and quality of Eugenia pyriformis Cambess. seedlings on
      substrate function and water levels.
AB  - The aim of this research was to evaluate the quality and photosynthetic
      metabolism of "uvaia" seedlings (Eugenia pyriformis Cambess.) on different
      substrates and water regimes. The seeds were sown in tubes of 50 x 190 mm in the
      following substrates: Sand (S), Latosol + Sand (L + S) (1:1), Latosol + Sand +
      Semi Decomposed Poultry Litter (L + S1 + PL) ( 1:1:0.5), Latosol + Sand + Semi
      Decomposed Poultry Litter (L + S2 + PL) (1:2:0.5), Latosol + Bioplant(r) (L + B)
      (1:1), and the water levels assessed were 50, 75 and 100% of water retention
      capacity. At 60, 90, 120 and 150 days the seedlings were evaluated according to
      their chlorophyll index, leaf area (cm2) and Dickson Quality Index (DQI) and at
      150 days their internal concentration of carbon (mol m-2 s-1), stomatal
      conductance (mol m-2 s-1), transpiration rate (mmol m-2 s-1), photosynthesis
      (umol m-2 s-1) and efficiency of water use (umol de CO2 / mmol de H2O). Until
      their 150th days, the seedlings had higher quality and photosynthetic metabolism
      when cultured with substrates containing latosol + sand + poultry litter on the
      two variations assessed and water retention capacity of 50%.

PMID- 25590740
TI  - Ultra-low temperature conservation of Brazilian pine embryogenic cultures.
AB  - This study aimed to establish a cryopreservation protocol for embryogenic
      cultures of A. angustifolia, enabling the ex situ conservation of the species.
      Embryogenic cultures were established from immature seeds and treated with
      variations of the cryoprotectant solutions SuDG, SoD and PVS2 prior to immersion
      in liquid nitrogen. Cell viability was evaluated after 30, 60 and 90 days of re
      growth. The highest re-growth without morphological alterations and with normal
      biochemical composition was obtained with the PVS2 solution with 40 min immersion
      in ethanol (-20  degrees C). This procedure opens new horizons for the ex situ
      conservation of the species genetic.

PMID- 25590739
TI  - Frequency and foraging behavior of Apis mellifera in two melon hybrids in
      Juazeiro, state of Bahia, Brazil.
AB  - The study was carried out to verify if there are differences in foraging
      frequency and behavior of Apis mellifera in two melon hybrids (10:00 - 'Yellow
      melon' and Sancho -'Piel de Sapo') in the municipality of Juazeiro, state of
      Bahia, Brazil. The frequency, behavior of visitors and the floral resource
      foraged were registered from 5:00 am to 6:00 pm. There was a significant
      difference in the frequency of visits when comparing hydrids (F = 103.74, p
      <0.0001), floral type (F = 47.25, p <0.0001) and resource foraged (F = 239.14, p
      <0.0001). The flowers of Sancho were more attractive to A. mellifera when
      compared with hybrid 10:00, which may be correlated to the morphology and floral
      resources available. This could be solved with scaled planting, avoiding the
      overlapping of flowering of both types.

PMID- 25590741
TI  - Elaboration of garlic and salt spice with reduced sodium intake.
AB  - Garlic and salt spice is widely used in Brazilian cookery, but it has a high
      sodium content; as high sodium intake has been strongly correlated to the
      incidence of chronic diseases. This study aimed to develop a garlic and salt
      spice with reduced sodium intake. Sensory evaluation was conducted by applying
      the spices to cooked rice. First, the optimal concentration of spice added during
      rice preparation was determined. Subsequently, seasonings (3:1) were prepared
      containing 0%, 50% and 25% less NaCl using a mixture of salts consisting of KCl
      and monosodium glutamate; a seasoning with a 0% NaCl reduction was established as
      a control. Three formulations of rice with different spices were assessed
      according to sensory testing acceptance, time-intensity and temporal domain of
      sensations. The proportions of salts used in the garlic and salt spice did not
      generate a strange or bad taste in the products; instead, the mixtures were less
      salty. However, the seasonings with lower sodium levels (F2 and F3) were better
      accepted in comparison to the traditional seasoning (F1). Therefore, a mixture of
      NaCl, KCl and monosodium glutamate is a viable alternative to develop a garlic
      and salt spice with reduced sodium intake. 

PMID- 25590742
TI  - Effect of storage in overcoming seed dormancy of Annona coriacea Mart. seeds.
AB  - The aim of this study was to evaluate the effect of pre-treatments on overcoming
      dormancy of A. coriacea seeds. Seeds were processed and stored in polyethylene
      bags at temperatures of at -18 degrees C (42% RH), 5 degrees C (34% RH), 15
      degrees C (60% RH) and 25 degrees C (34% RH), during 0, 30, 60, 90, 120 and 150
      days. After storage, seeds were immersed in 350 mg.L-1 gibberellic acid for 144
      hours. Sowing was carried out in plastic bags containing Red Latosol +
      Bioplant(r). Moisture content, emergence percentage, emergence speed index,
      length and dry mass of seedlings, were evaluated. The experimental design was
      completely randomized in a factorial with four replications of 50 seeds each. The
      seed storage at 5 degrees C and subsequent immersion in gibberellic acid was
      efficient to reach high percentage, emergence speed and plant growth. A. coriacea
      seeds showed non-deep simple morphophysiological dormancy wherein the
      physiological component can be overcome after the seeds are storage at 5 degrees
      C for a maximum period of 53 days and subsequent immersed in exogenous GA (350
      mg.L-1 for 144 hours).

PMID- 25590743
TI  - Pollination of rapeseed (Brassica napus) by Africanized honeybees (Hymenoptera:
      Apidae) on two sowing dates.
AB  - In this study, performed in the western part of the state of Parana, Brazil, two
      self-fertile hybrid commercial rapeseed genotypes were evaluated for yield
      components and physiological quality using three pollination tests and spanning
      two sowing dates. The treatments consisted of combinations of two rapeseed
      genotypes (Hyola 61 and Hyola 433), three pollination tests (uncovered area,
      covered area without insects and covered area containing a single colony of
      Africanized Apis mellifera honeybees) and two sowing dates (May 25th, 2011 and
      June 25th, 2011). The presence of Africanized honeybees during flowering time
      increased the productivity of the rapeseed. Losses in the productivity of the
      hybrids caused by weather conditions unfavorable for rapeseed development were
      mitigated through cross-pollination performed by the Africanized honeybees.
      Weather conditions may limit the foraging activity of Africanized honeybees,
      causing decreased cross-pollination by potential pollinators, especially the
      Africanized A. mellifera honeybee. The rapeseed hybrids respond differently
      depending on the sowing date, and the short-cycle Hyola 433 hybrid is the most
      suitable hybrid for sowing under less favorable weather conditions.

PMID- 25590745
TI  - Behavior and performance of sows fed different levels of fiber and reared in
      individual cages or collective pens.
AB  - Sixteen pregnant sows were used. The experimental design was completely
      randomized with a 2x2 factorial scheme consisting of two housing systems
      (individual cages and collective pens) and two diets (low [2.67%] and high
      [13.14%] level of crude fiber). Physiological, behavioral, environmental, and
      hormonal parameters were studied. In addition, the following productive and
      reproductive parameters were evaluated: weight gain, feed intake, feed conversion
      of the sow and piglets, number of piglets born dead and alive, number and weight
      at weaning, and backfat thickness of sows. Pregnant sows reared in collective
      pens and fed a high-fiber diet exhibited better physiological responses,
      indicating greater comfort and better animal welfare. The environmental variables
      were close to the comfort zone of the animals. In addition to providing a more
      comfortable environment, housing pigs in collective pens reduced stereotypy,
      permitting the sows to express a more natural behavior. The high-fiber diet did
      not interfere with female productive performance. Tifton hay can therefore be
      indicated as an alternative for the formulation of sow diets to improve animal
      welfare.

PMID- 25590746
TI  - Feasible domain of Walker's unsteady wall-layer model for the velocity profile in
      turbulent flows.
AB  - The present work studies, in detail, the unsteady wall-layer model of Walker et
      al. (1989, AIAA J., 27, 140 - 149) for the velocity profile in turbulent flows.
      Two new terms are included in the transcendental nonlinear system of equations
      that is used to determine the three main model parameters. The mathematical and
      physical feasible domains of the model are determined as a function of the non
      dimensional pressure gradient parameter (p+). An explicit parameterization is
      presented for the average period between bursts (T+B), the origin of time (t+0 )
      and the integration constant of the time dependent equation (A0) in terms of p+.
      In the present procedure, all working systems of differential equations are
      transformed, resulting in a very fast computational procedure that can be used to
      develop real-time flow simulators.

PMID- 25590744
TI  - Stenospermy and seed development in the "Brazilian seedless" variety of sugar
      apple (Annona squamosa).
AB  - Stenospermy was identified in naturally occurring sugar-apple (Annona squamosa)
      mutants with great potential for use in genetic improvement programs. However, to
      date, there have been no detailed studies of the development of aspermic fruit in
      this species. The aim of the present study was to characterize the anatomy of
      developing fruit in the 'Brazilian Seedless' mutant. Flower buds in pre-anthesis
      and developing fruits were subjected to common plant anatomy techniques. The
      abnormal ovules are unitegmic and orthotropic and have a long funiculus. There is
      evidence of fertilization, including the presence of embryos in early development
      and the proliferation of starch grains in the embryo sac. However, the embryos
      and embryo sac degenerate, although this does not affect pericarp development.
      Ovule abortion does not occur. The perisperm, which is formed from the peripheral
      layers of the nucellus, fills the cavity left by the embryo sac. The mature fruit
      contains numerous small sterile seeds with abundant perisperm and unlignified
      integument that is restricted to the micropylar region. The majority of perisperm
      cells are living and appear to be metabolically active in the periphery.
      Therefore, stenospermy leads to the formation of sterile seeds in A. squamosa,
      and the perisperm possibly play an important role in fruit development. 

PMID- 25590748
TI  - The environmental risk as a culture in the Sinos Valley, Brazil.
AB  - The proposal of analysis of the social-environmental perception will be developed
      from the discourse as a constitutive element of reality. The discourse practices
      and their concretion will be the source of meaning and social-cultural value.
      Thus, the chosen research method was the qualitative and quantitative case study.
      In the first part of the text we will recapture a theoretical input by Mary
      Douglas on risk and culture, as well as on the acceptance of the risks in
      society. In the second part, we cover a few data of the case of the risks
      resulting from the tanning industry and on how the society of the "Vale do Rio
      dos Sinos" relates to these risks. In this article we conclude that risk
      perception of the population is directly related with past experiences, thus,
      assigning a meaning to all new events. This meaning is the result of a
      sociocultural construction. It is worth noting that behind this history, there
      are basic issues related to population survival, i.e., both the industrialists
      and workers establish partnerships when the society creates a movement against
      the leather industry.

PMID- 25590750
TI  - Nuclear G protein signaling: new tricks for old dogs.
AB  - According to the standard model of G protein-coupled receptor (GPCR) signaling,
      GPCRs are localized to the cell membrane where they respond to extracellular
      signals. Stimulation of GPCRs leads to the activation of heterotrimeric G
      proteins and their intracellular signaling pathways. However, this model fails to
      accommodate GPCRs, G proteins, and their downstream effectors that are found on
      the nuclear membrane or in the nucleus. Evidence from isolated nuclei indicates
      the presence of GPCRs on the nuclear membrane that can activate similar G protein
      dependent signaling pathways in the nucleus as at the cell surface. These
      pathways also include activation of cyclic adenosine monophosphate, calcium and
      nitric oxide synthase signaling in cardiomyocytes. In addition, a number of
      distinct heterotrimeric and monomeric G proteins have been found in the nucleus
      of various cell types. This review will focus on understanding the function of
      nuclear G proteins with a focus on cardiac signaling where applicable.

PMID- 25590749
TI  - A nonpeptide angiotensin II type 2 receptor agonist prevents renal inflammation
      in early diabetes.
AB  - We hypothesized that direct AT2R stimulation improves albuminuria in diabetes by
      preventing renal inflammation and improving oxidative stress. Normoglycemic
      controls (NCs) and streptozotocin-induced diabetes Sprague-Dawley rats (DM) were
      treated for 4 weeks with vehicle (V) or the AT2R agonist Compound 21 (C21). At
      the end of study, we evaluated blood pressure, urinary albumin to creatinine
      ratio (UACR), renal interstitial fluid (RIF) levels of tumor necrosis factor
      alpha (TNF-alpha), interleukin 6 (IL-6), nitric oxide (NO), cGMP, and 8
      isoprostane, and renal expression of TNF-alpha, IL-6, and AT2R. There were no
      significant differences in blood pressure between different treatments. DM rats
      demonstrated increased UACR, RIF TNF-alpha, IL-6 and 8-isoprostane, and messenger
      RNA (mRNA) for TNF-alpha and IL-6. DM rats also had reduced RIF NO and cGMP. C21
      treatment of DM rats limited the increase in UACR, normalized RIF TNF-alpha, IL-6
      and 8-isoprostane, and in mRNA for TNF-alpha and IL-6, and increased RIF NO and
      cGMP. In NC rats, C21 treatment did not change these parameters. AT2R mRNA and
      protein expressions increased in DM rats compared with NC but were not influenced
      by C21 treatment. We conclude that direct AT2R stimulation in diabetic rats
      improves diabetic albuminuria through the prevention of renal inflammation and
      improved production of NO and cGMP. 

PMID- 25590751
TI  - Influence of silicon dioxide capping layers on pore characteristics in
      nanocrystalline silicon membranes.
AB  - Porous nanocrystalline silicon (pnc-Si) membranes are a new class of membrane
      material with promising applications in biological separations. Pores are formed
      in a silicon film sandwiched between nm thick silicon dioxide layers during rapid
      thermal annealing. Controlling pore size is critical in the size-dependent
      separation applications. In this work, we systematically studied the influence of
      the silicon dioxide capping layers on pnc-Si membranes. Even a single nm thick
      top oxide layer is enough to switch from agglomeration to pore formation after
      annealing. Both the pore size and porosity increase with the thickness of the top
      oxide, but quickly reach a plateau after 10 nm of oxide. The bottom oxide layer
      acts as a barrier layer to prevent the a-Si film from undergoing homo-epitaxial
      growth during annealing. Both the pore size and porosity decrease as the
      thickness of the bottom oxide layer increases to 100 nm. The decrease of the pore
      size and porosity is correlated with the increased roughness of the bottom oxide
      layer, which hinders nanocrystal nucleation and nanopore formation. 

PMID- 25590752
TI  - What's one phosphate between friends (and foe)?
AB  - Body surfaces are colonized by resident microbes that are remarkably resilient to
      recurrent immune responses. In the latest issue of Science, Cullen et al. (2015)
      report that, contrary to prevailing assumptions, bacteria of the colonizing
      microbiota are resistant to antimicrobial peptides, and identify a common
      mechanism of resistance.

PMID- 25590753
TI  - Murine gut microbiota-diet trumps genes.
AB  - Both environmental factors and host genetics shape the composition of gut
      microbiota in mammals, but what matters more is insufficiently understood. In
      this issue of Cell Host & Microbe, Carmody et al. (2015) show that diet can
      overrule genotype-related differences in gut microbiota composition in different
      mouse populations.

PMID- 25590754
TI  - Interferons coordinate a multifaceted defense.
AB  - While interferons help kill virally infected cells, they can also promote
      systemic immune responses in distant tissues. In this issue of Cell Host &
      Microbe, Sun et al. (2015) demonstrate that type I interferon induces intestinal
      epithelial proliferation. This may help maintain a healthy gut and promote
      recovery from viral gastroenteritis.

PMID- 25590755
TI  - HIV-1/HIV-2 versus SAMHD1 restriction: a tale of two viruses.
AB  - The deoxynucleoside triphosphate triphosphohydrolase SAMHD1 is a myeloid cell
      specific retroviral restriction factor that can be inactivated by viral protein
      Vpx from HIV-2 and certain SIV. In this issue of Cell Host & Microbe, Kyei et al.
      (2015) report that cyclin L2 enhances HIV-1 infection in macrophages by
      regulating SAMHD1.

PMID- 25590756
TI  - PfEMP1's magical embrace of EPCR.
AB  - Since discovering PfEMP1 virulence proteins in Plasmodium falciparum,
      malariologists have struggled to reconcile their limitless sequence diversity
      with their binding to relatively few host receptors. In this issue of Cell Host &
      Microbe, Lau et al. (2015) explore how diverse PfEMP1s embrace EPCR, promoting
      parasite survival and killing African children.

PMID- 25590757
TI  - Heterogeneous host-pathogen encounters: act locally, think globally.
AB  - Recent studies are revealing astonishing heterogeneity in host-pathogen
      interactions occurring simultaneously within the same host tissue. As highlighted
      in this review, growing knowledge of the in vivo complexity is altering our
      understanding of infection biology. In particular, pathogen subsets reside in
      diverse tissue microenvironments and detect and respond to local conditions. The
      individual pathogen-host encounters have disparate outcomes, depending on
      differential molecular interactions. As a result, disease progression can result
      from failure to control individual infection foci, despite successful eradication
      of others, and antibiotic therapy can be delayed by distinct pre-existing
      pathogen subsets. Together, these data are unraveling rich biology with
      implications for infectious disease progression and control.

PMID- 25590759
TI  - The integrase cofactor LEDGF/p75 associates with Iws1 and Spt6 for
      postintegration silencing of HIV-1 gene expression in latently infected cells.
AB  - The persistence of a latent reservoir containing transcriptionally silent, but
      replication-competent, integrated provirus is a serious challenge to HIV
      eradication. HIV integration is under the control of LEDGF/p75, the cellular
      cofactor of viral integrase. Investigating possible postintegration roles for
      LEDGF/p75, we find that LEDGF/p75 represses HIV expression in latently infected
      cells. LEDGF/p75 associated with two proteins involved in the control of gene
      expression and chromatin structure, Spt6 and Iws1, to form a stable complex. Iws1
      plays a role in the establishment of latent infection, whereas Spt6 functions to
      recruit Iws1 and LEDGF/p75 to the silenced provirus and maintains histone
      occupancy at the HIV promoter. In latently infected cells, depletion of the
      complex results in reactivation of HIV expression Altogether, our results
      indicate that a complex containing LEDGF/p75, Iws1, and Spt6 participates in
      regulating postintegration steps of HIV latency. 

PMID- 25590758
TI  - Hepcidin-induced hypoferremia is a critical host defense mechanism against the
      siderophilic bacterium Vibrio vulnificus.
AB  - Hereditary hemochromatosis, an iron overload disease caused by a deficiency in
      the iron-regulatory hormone hepcidin, is associated with lethal infections by
      siderophilic bacteria. To elucidate the mechanisms of this susceptibility, we
      infected wild-type and hepcidin-deficient mice with the siderophilic bacterium
      Vibrio vulnificus and found that hepcidin deficiency results in increased
      bacteremia and decreased survival of infected mice, which can be partially
      ameliorated by dietary iron depletion. Additionally, timely administration of
      hepcidin agonists to hepcidin-deficient mice induces hypoferremia that decreases
      bacterial loads and rescues these mice from death, regardless of initial iron
      levels. Studies of Vibrio vulnificus growth ex vivo show that high iron sera from
      hepcidin-deficient mice support extraordinarily rapid bacterial growth and that
      this is inhibited in hypoferremic sera. Our findings demonstrate that hepcidin
      mediated hypoferremia is a host defense mechanism against siderophilic pathogens
      and suggest that hepcidin agonists may improve infection outcomes in patients
      with hereditary hemochromatosis or thalassemia.

PMID- 25590761
TI  - Clinical efficacy of formula-based bifrontal versus right unilateral
      electroconvulsive therapy (ECT) in the treatment of major depression among
      elderly patients: a pragmatic, randomized, assessor-blinded, controlled trial.
AB  - BACKGROUND: No prior study has compared the efficacy of bifrontal (BF) vs right
      unilateral (RUL) electroconvulsive therapy (ECT) by including the subgroup that
      is most likely to receive it: only elderly patients with major depression (MD).
      METHODS: This single-site, randomized, assessor-blinded, controlled trial was
      conducted from 2009 to 2013. Seventy-three elderly patients with MD, unipolar and
      bipolar, were treated with a course of formula-based BF ECT or RUL ECT. The 17
      item Hamilton Rating Scale for Depression (HRSD17) was used to measure efficacy.
      Safety was assessed with the Mini Mental State Examination (MMSE). RESULTS: Both
      electrode placements resulted in highly significant downward trends in symptom
      severity (all p<0.001), with a non-significant difference between methods
      (p=0.703). At the end of the ECT course, response rates for the BF and RUL group
      were 63.9% and 67.6%, respectively. Short-term remission, defined as an HRSD17
      score<=7, was achieved in 14 (38.9%) patients in the BF group and 19 (51.4%)
      patients in the RUL group. Global cognitive function, as measured by the MMSE,
      did not deteriorate in the two treatment groups. LIMITATIONS: The small number of
      subjects may have led to reduced power to detect real differences. The MMSE is
      not sufficient to ascertain the negative effect of ECT on cognition. CONCLUSIONS:
      This study indicates that formula-based BF and RUL ECT are equally efficacious,
      and that remission rates of formula-based dosing are lower than those previously
      reported for titrated dosing, in a clinical sample of elderly patients with MD.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01559324.

PMID- 25590762
TI  - Prevalence and incidence of perinatal depression and depressive symptoms among
      Mexican women.
AB  - BACKGROUND: The aim of this study was to assess point and period prevalence and
      incidence of perinatal depression in Mexican women. METHODS: The Structured
      Clinical Interview for DSM-IV and the Patient Health Questionnaire (PHQ-9) were
      administered at three points in time to 210 women: during the third trimester of
      pregnancy, at six weeks and at six months after delivery. RESULTS: Prevalence of
      prenatal depression was 9.0%, and 13.8% at six weeks and 13.3% at six months
      postpartum. Incidence of postpartum depression (PPD) was 10.0% at six weeks and
      8.2% at six months. Prevalence of prenatal depressive symptoms was 16.6%; and
      17.1% at six weeks and 20.0% at six months postpartum. Incidence of postpartum
      depressive symptoms (PPDS) was 11.4% at six weeks and 9.0% at six months. At six
      months postpartum, women with depression were younger (OR=2.45, p=0.02), had
      fewer years' schooling (OR=5.61, p=0.00), were unpartnered (OR=3.03, p=0.01),
      unemployed (OR=3.48, p=0.00) and poorer (OR=4.00, p=0.00) than women without
      depression. LIMITATIONS: 25% of the initial sample was not retained to complete
      the three assessments. Non completers were younger, less educated and reported
      more depressive symptoms. This may have resulted in an underestimation of
      prevalence. CONCLUSIONS: This is the first longitudinal study in Latin America to
      assess perinatal depression at three different points in times, reporting point
      and period prevalence and incidence of clinical depression and depressive
      symptoms. Most LA countries have yet to recognize the importance of providing
      mental health care for expectant and postpartum mothers to reduce disability in
      mothers and infants.

PMID- 25590760
TI  - A PfRH5-based vaccine is efficacious against heterologous strain blood-stage
      Plasmodium falciparum infection in aotus monkeys.
AB  - Antigenic diversity has posed a critical barrier to vaccine development against
      the pathogenic blood-stage infection of the human malaria parasite Plasmodium
      falciparum. To date, only strain-specific protection has been reported by trials
      of such vaccines in nonhuman primates. We recently showed that P. falciparum
      reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for
      erythrocyte invasion, is highly susceptible to vaccine-inducible strain
      transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based
      vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based
      vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P.
      falciparum challenge and show that such protection can be achieved by a human
      compatible vaccine formulation. Protection was associated with anti-PfRH5
      antibody concentration and in vitro parasite-neutralizing activity, supporting
      the use of this in vitro assay to predict the in vivo efficacy of future vaccine
      candidates. These data suggest that PfRH5-based vaccines have potential to
      achieve strain-transcending efficacy in humans.

PMID- 25590763
TI  - Autonomic arousal in childhood anxiety disorders: associations with state anxiety
      and social anxiety disorder.
AB  - BACKGROUND: Psychophysiological theories suggest that individuals with anxiety
      disorders may evidence inflexibility in their autonomic activity at rest and when
      responding to stressors. In addition, theories of social anxiety disorder, in
      particular, highlight the importance of physical symptoms. Research on autonomic
      activity in childhood (social) anxiety disorders, however, is scarce and has
      produced inconsistent findings, possibly because of methodological limitations.
      METHOD: The present study aimed to account for limitations of previous studies
      and measured respiratory sinus arrhythmia (RSA) and heart rate (HR) using
      Actiheart heart rate monitors and software (Version 4) during rest and in
      response to a social and a non-social stressor in 60 anxious (30 socially anxious
      and 30 'other' anxious), and 30 nonanxious sex-and age-matched 7-12 year olds. In
      addition, the effect of state anxiety during the tasks was explored. RESULTS: No
      group differences at rest or in response to stress were found. Importantly,
      however, with increases in state anxiety, all children, regardless of their
      anxiety diagnoses showed less autonomic responding (i.e., less change in HR and
      RSA from baseline in response to task) and took longer to recover once the
      stressor had passed. LIMITATIONS: This study focused primarily on parasympathetic
      arousal and lacked measures of sympathetic arousal. CONCLUSION: The findings
      suggest that childhood anxiety disorders may not be characterized by inflexible
      autonomic responding, and that previous findings to the contrary may have been
      the result of differences in subjective anxiety between anxious and nonanxious
      groups during the tasks, rather than a function of chronic autonomic
      dysregulation.

PMID- 25590764
TI  - Magnitude and risk factors for postpartum symptoms: a literature review.
AB  - BACKGROUND: The prevalence of postpartum depression worldwide varies from 0.5% to
      60.8% in the first 12 months postpartum using self-reported questionnaire. This
      review aims to update the current magnitude of postpartum depression based on
      self-reported questionnaire and clinical interview and explore its associated
      factors in developed and developing countries. METHODS: A literature search
      conducted between 2005 and 2014 identified 203 studies, of which 191 used self
      reported questionnaire in 42 countries and 21 used structured clinical interview
      in 15 countries. Nine studies used a combination of self-reported questionnaire
      and clinical interview. RESULT: The prevalence of postpartum depression varies
      from 1.9% to 82.1% in developing countries and from 5.2% to 74.0% in developed
      countries using self-reported questionnaire. Structured clinical interview shows
      a much lower prevalence range from 0.1% in Finland to 26.3% in India. Antenatal
      depression and anxiety, previous psychiatric illness, poor marital relationship,
      stressful life events, negative attitude towards pregnancy, and lack of social
      support are significant contributors to postpartum depression. LIMITATION: All
      studies are included irrespective of the methodological quality, such as small
      sample size and their inclusion could affect the generalizability of the results.
      CONCLUSION: The current prevalence of postpartum depression is much higher than
      that previously reported, and similar risk factors are documented. A culturally
      sensitive cut-off score with adequate psychometric properties of the screening
      instruments should be available. In future studies, examining the physical,
      biological, and cultural factors in qualitative studies and in those with
      adequate methodological qualities is recommended.

PMID- 25590765
TI  - Newer Therapies for Management of Stable Ischemic Heart Disease With Focus on
      Refractory Angina.
AB  - Ischemic heart disease remains a major public health problem nationally and
      internationally. Stable ischemic heart disease (SIHD) is one of the clinical
      manifestations of ischemic heart disease and is generally characterized by
      episodes of reversible myocardial demand/supply mismatch, related to ischemia or
      hypoxia, which are usually inducible by exercise, emotion, or other stress and
      reproducible-but which may also be occurring spontaneously. Improvements in the
      treatment of acute coronary syndromes along with increasing prevalence of
      cardiovascular risk factors, including diabetes and obesity, have led to
      increasing population of patients with SIHD. A significant number of these
      continue to have severe angina despite medical management and revascularization
      procedures performed and may progress to refractory angina. This article reviews
      the newer therapies in the treatment of SIHD with special focus in treating
      patients with refractory angina.

PMID- 25590767
TI  - Isolation of carboxylic acid-protected Au25 clusters using a borohydride
      purification strategy.
AB  - We report the synthesis of 11-mercaptoundecanoic acid (11-MUA) and 16
      mercaptohexadecanoic acid (16-MHA) protected Au25 clusters with moderate yields
      (~15%) using a NaBH4 purification strategy. UV-vis spectroscopy, transmission
      electron microscopy (TEM), and matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry were employed to study the entire process of the
      isolation of 11-MUA-protected Au25 clusters from a polydisperse Au cluster
      solution. UV-vis and TEM data clearly show the formation of a polydisperse
      mixture, which upon the addition of NaBH4 leads to the growth and precipitation
      of non-Au25 clusters, leaving the Au25 clusters behind. MALDI MS shows the
      molecular ion peak for the 11-MUA-protected Au25 cluster. 11-MUA-protected Au25
      clusters in THF were purified by slowly increasing the pH of the solution, which
      leads to the complete deprotonation of carboxyl groups on the surface and
      eventually precipitation of Au25 clusters. Further protonation of these clusters
      by acetic acid leads to their solubilization in THF. These results show that,
      owing to the inherent stability of Au25 clusters, a NaBH4 purification strategy
      can be used to isolate Au25 clusters with surface carboxylic acid functionalities
      from a polydisperse Au cluster solution. 

PMID- 25590766
TI  - Establishment of developmental charts for the larvae of the blow fly Calliphora
      vicina using quantile regression.
AB  - Developmental data of necrophagous blow fly species can be used to estimate a
      minimum postmortem interval (PMImin) in death investigations by estimating the
      age of larvae sampled from the cadaver. The most important parameter used in this
      age estimation is the increase in larval length during growth. Larval length can
      be compared to species-specific reference data to get an age estimate for the
      larval specimen. The exploration of this type of data and the use of an
      appropriate statistical method are the major challenges in evaluating forensic
      entomological data sets. In Europe, Calliphora vicina is one of the most dominant
      species with forensic entomological relevance. Despite its frequency and
      importance, there are currently no published developmental studies for German
      populations of this blow fly that can be referenced for larval age estimations.
      This is regrettable because the geographical origin of different populations may
      lead to phenotypic plasticity in the same species and population-specific growth
      patterns that differ from published data sets. To address this shortcoming, the
      objective of the present research was to generate growth data for C. vicina which
      can be used for age estimation in German casework. We present, for the first
      time, local developmental data for the larval stages of German C. vicina, reared
      at three constant temperatures (15, 20 and 25 degrees C) and compare the results
      with published studies on C. vicina development from elsewhere. To analyse the
      development we chose a quantile mixed effects model because of its robustness and
      insensitivity towards outliers. Quantile regression was developed as an extension
      of the linear model to estimate rates of change in all parts of the distribution
      of a response variable and to discover more useful predictive relationships
      between variables. By applying a linear quantile mixed effect model, we estimated
      the 0.1 and 0.9 quantile functions of the larval age for each temperature.
      Graphically, these quantile functions act like reference bands and therefore,
      plots for larval stages 1-3 can be used to estimate the age of a larva.
      Nevertheless, the post-feeding stage still remains difficult to describe with
      linear models and need to be further investigated. A comparison of the results
      from this present study with the currently applied methods for age estimation of
      C. vicina still demonstrates the importance of collecting growth rates for local
      blow fly populations and of standardising experimental designs and statistical
      analyses. 

PMID- 25590768
TI  - Marteilia sp. and other parasites and pathological conditions in Solen marginatus
      populations along the Galician coast (NW Spain).
AB  - This paper reports the results of the survey developed after the first detection
      of protozoan Marteilia sp. infection of the grooved razor shell Solen marginatus
      (Pulteney, 1799) from Galicia (NW Spain) in 2006. Furthermore, we analysed other
      parasites and pathological conditions found in grooved razor shell populations
      throughout this survey, such as metacercariae of trematodes, prokaryotic
      infections and disseminated neoplasms, some of which could cause moderate or
      severe damage to the host depending on the intensity of infection. A total of 17
      natural beds distributed along the Galician coast were analysed, and Marteilia
      sp. was detected in 6 of them with low prevalence, moderate intensity and no
      negative effects over the populations. 

PMID- 25590769
TI  - Differential expression of serine protease inhibitors 1 and 2 in Crassostrea
      corteziensis and C. virginica infected with Perkinsus marinus.
AB  - Proliferation of Perkinsus marinus (Dermo) in vitro is inhibited by the action of
      2 serine protease inhibitors belonging to the I-84 family. We compared the levels
      of expression of serine protease inhibitors 1 and 2 (SPI-1 and SPI-2) in 2 oyster
      species (Crassostrea virginica and C. corteziensis) inoculated with the parasite
      P. marinus. C. virginica is well known to be susceptible to this parasite,
      whereas C. corteziensis is apparently more tolerant. Oysters were inoculated with
      trophozoites (1 * 106 trophozoites oyster-1) of P. marinus while control oysters
      were injected with saline solution. Oysters were maintained in a closed water
      system for 2 wk. The oysters were then sacrificed and parasite burden,
      histological damage, and gene expression were evaluated. The results showed that
      the challenged oysters presented a significant increase in parasite burden, which
      generated histological damage in digestive gland and gills. Quantitative PCR
      detected significant differences in SPI-1 and SPI-2 expression levels in the 2
      oyster species, with C. corteziensis showing higher expression levels than C.
      virginica as a response to P. marinus inoculation. Our results provide valuable
      information for the understanding of the defense response in C. corteziensis and
      a possible explanation for its tolerance to the parasite. 

PMID- 25590770
TI  - Recruitment of the parasitic pea crab Nepinnotheres novaezelandiae into green
      lipped mussels Perna canaliculus.
AB  - Pea crab species are globally ubiquitous parasites of marine bivalves including
      several major aquaculture species. However, little is known about the
      environmental factors that affect their recruitment into aquacultured mussels.
      The effect of depth and distance from shore on the recruitment of the parasitic
      pea crab Nepinnotheres novaezelandiae into New Zealand green-lipped mussels Perna
      canaliculus was examined with a field experiment. The incidence of pea crab
      infection of mussels over 295 d was nearly double when deployed at 5-10 m depth
      (1.97%) compared to 20-30 m depth (0.96%), although it was not significantly
      different due to the overall low period prevalence in the experimental
      population. The sex ratio of crabs recovered was significantly skewed towards
      females with a ratio of 1:14 (chi = 11.3, p < 0.001). Infection with pea crabs
      was found to significantly reduce final mussel shell height on average by 28%
      (21.0 mm) over 295 d (Mann-Whitney U = 6.0, p < 0.0001). This study confirms that
      parasitism of green-lipped mussels by pea crabs has a significant impact on the
      growth of the mussels and suggests that the incidence of pea crabs will be higher
      in shallower water and when mussels are in closer proximity to the shore. With no
      control methods available for preventing pea crab infection, these results
      suggest that moving mussel farms offshore has the potential to reduce the
      incidence of pea crabs in mussels and warrants larger-scale assessment.

PMID- 25590771
TI  - Disease, parasite, and commensal prevalences for blue crab Callinectes sapidus at
      shedding facilities in Louisiana, USA.
AB  - Blue crab diseases, parasites, and commensals are not well studied in the Gulf of
      Mexico, and their prevalence rates have only been sporadically determined.
      Commercial soft shell shedding facilities in Louisiana experience high mortality
      rates of pre-molt crabs, and some of these deaths may be attributable to diseases
      or parasites. During the active shedding season in 2013, we determined the
      prevalence of shell disease, Vibrio spp., Lagenophrys callinectes, and
      Hematodinium perezi at 4 commercial shedding facilities along the Louisiana
      coast. We also detected Ameson michaelis and reo-like virus infections. Shell
      disease was moderately prevalent at rates above 50% and varied by shedding
      facility, collection month, and crab size. Vibrio spp. bacteria were prevalent in
      the hemolymph of 37% of the pre-molt crabs. Lagenophrys callinectes was highly
      prevalent in the pre-molt crabs, but because it is a commensal species, it may
      not cause high mortality rates. Hematodinium perezi was absent in all pre-molt
      crabs. 

PMID- 25590772
TI  - Eroded swimmeret syndrome in female crayfish Pacifastacus leniusculus associated
      with Aphanomyces astaci and Fusarium spp. infections.
AB  - We describe a novel syndrome in crayfish, eroded swimmeret syndrome (ESS),
      affecting wild female signal crayfish Pacifastacus leniusculus. ESS causes
      partial or total swimmeret erosion. We observed ESS only in female signal
      crayfish larger than 40 mm carapace length, i.e. sexually mature and probably
      having carried eggs at least once. The eroded swimmerets were melanised,
      indicating a crayfish immune system response. We isolated Fusarium tricinctum
      species complex (SC), F. sambucinum SC, Saprolegnia parasitica and S. australis
      from the melanised tissue of the eroded swimmerets. ESS includes chronic
      Aphanomyces astaci infection and a secondary infection by Fusarium sp. In Sweden,
      we found female signal crayfish with ESS in 6 out of 11 populations with a
      prevalence below 1% in lakes with commercially productive signal crayfish
      populations and higher than 29% in lakes with documented signal crayfish
      population crashes. In Finland, the ESS prevalence was from 3.4 to 6.2% in a
      commercially productive population. None of the sampled male signal crayfish
      showed signs of ESS. A caging experiment indicated that females with at least 1
      lost swimmeret carried on average 25% fewer fertilized eggs compared to females
      with intact swimmerets. ESS could significantly reduce individual female
      fecundity and thus could also affect fecundity at the population level. The
      decline in reproductive success due to ESS could be among the factors
      contributing to fluctuations in wild signal crayfish populations. 

PMID- 25590773
TI  - Batrachochytrium dendrobatidis in natural and farmed Louisiana crayfish
      populations: prevalence and implications.
AB  - The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) has been linked
      to global declines and extinctions of amphibians, making it one of the most
      devastating wildlife pathogens known. Understanding the factors that affect
      disease dynamics in this system is critical for mitigating infection and
      protecting threatened species. Crayfish are hosts of this pathogen and can
      transmit Bd to amphibians. Because they co-occur with susceptible amphibian
      communities, crayfish may be important alternative hosts for Bd. Understanding
      the prevalence and seasonal dynamics of crayfish infections is of agricultural
      and ecological interest in areas where crayfish are farmed and traded for human
      consumption. We conducted a survey of Bd in farmed and natural crayfish
      (Procambarus spp.) populations in Louisiana, USA. We found that Bd prevalence and
      infection intensity was low in both farmed and native populations and that
      prevalence varied seasonally in wild Louisiana crayfish. This seasonal pattern
      mirrors that seen in local amphibians. As crayfish are an important globally
      traded freshwater taxon, even with low prevalence, they could be an important
      vector in the spread of Bd. 

PMID- 25590774
TI  - Batrachochytrium dendrobatidis exposure effects on foraging efficiencies and body
      size in anuran tadpoles.
AB  - Chytridiomycosis, the amphibian disease caused by the pathogenic fungus
      Batrachochytrium dendrobatidis (Bd), is fatal to adults of many species. Bd is
      largely sublethal to amphibian larvae; however, it is known to reduce larval
      (i.e. tadpole) growth rates, with possible long-term effects on population
      dynamics and fitness. We conducted an experiment to test how Bd altered southern
      leopard frog Lithobates sphenocephalus tadpole mouthpart damage, percentage of
      food ingested, and subsequent body size. We examined our results using path
      analyses. We hypothesized that Bd would increase mouthpart damage, causing less
      food to be ingested, and ultimately reduce body size. In our model, both Bd
      exposure and increased mouthpart damage significantly reduced food ingested and
      subsequent body size. However, our study provides evidence against the long
      standing hypothesis of mouthpart damage as a pathway for Bd-induced reductions in
      larval group. Here we provide evidence for reduced foraging efficiency
      (percentage of food ingested) as a mechanism for Bd-induced reductions in body
      size. This work highlights the importance of studying the sublethal effects of Bd
      on larval amphibians. 

PMID- 25590775
TI  - Itraconazole treatment reduces Batrachochytrium dendrobatidis prevalence and
      increases overwinter field survival in juvenile Cascades frogs.
AB  - The global spread of the fungal pathogen Batrachochytrium dendrobatidis (Bd) has
      led to widespread extirpation of amphibian populations. During an intervention
      aimed at stabilizing at-risk populations, we treated wild-caught Cascades frogs
      Rana cascadae with the antifungal drug itraconazole. In fall 2012, we collected
      60 recently metamorphosed R. cascadae from 1 of the 11 remnant populations in the
      Cascades Mountains (CA, USA). Of these, 30 randomly selected frogs were treated
      with itraconazole and the other 30 frogs served as experimental controls; all
      were released at the capture site. Bd prevalence was low at the time of treatment
      and did not differ between treated frogs and controls immediately following
      treatment. Following release, Bd prevalence gradually increased in controls but
      not in treated frogs, with noticeable (but still non-significant) differences 3
      wk after treatment (27% [4/15] vs. 0% [0/13]) and strong differences 5 wk after
      treatment (67% [8/12] vs. 13% [1/8]). We did not detect any differences in Bd
      prevalence and load between experimental controls and untreated wild frogs during
      this time period. In spring 2013, we recaptured 7 treated frogs but none of the
      experimental control frogs, suggesting that over-winter survival was higher for
      treated frogs. The itraconazole treatment did appear to reduce growth rates:
      treated frogs weighed 22% less than control frogs 3 wk after treatment (0.7 vs.
      0.9 g) and were 9% shorter than control frogs 5 wk after treatment (18.4 vs. 20.2
      mm). However, for critically small populations, increased survival of the most at
      risk life stage could prevent or delay extinction. Our results show that
      itraconazole treatment can be effective against Bd infection in wild amphibians,
      and therefore the beneficial effects on survivorship may outweigh the detrimental
      effects on growth. 

PMID- 25590776
TI  - Asian strain of Batrachochytrium dendrobatidis is widespread in the Western
      Ghats, India.
AB  - We investigated the distribution of Batrachochytrium dendrobatidis (Bd) fungal
      infections in amphibians of the Western Ghats mountain range in India, based on
      data from 497 samples. Eight individuals were positive, with genomic equivalents
      ranging from 2 to 785 zoospores. A single widespread Bd strain identical to the
      haplotype endemic to Asia was isolated. Our findings suggest that
      chytridiomycosis is widespread among the endemic and threatened amphibians of the
      entire stretch of the Western Ghats. An ecological niche-based prediction model
      based on all Bd-positive reports from the Western Ghats to date suggested a
      higher probability of infection in the central Western Ghats of Karnataka and
      northern Kerala states, which host a rich diversity of endemic and threatened
      amphibians. 

PMID- 25590777
TI  - Anisakis spp. induced granulomatous dermatitis in a harbour porpoise Phocoena
      phocoena and a bottlenose dolphin Tursiops truncatus.
AB  - Cetaceans are well known definitive hosts of parasitic nematodes of the genus
      Anisakis (Nematoda: Anisakidae). Anisakid nematodes are also a health hazard for
      humans, potentially causing gastrointestinal infections or allergic reactions
      following the consumption of infected fish. In marine mammals, the nematodes
      develop from third-stage larvae to adults in the stomachs. In the first (or fore
      ) stomach, these parasites are typically associated with mucosal ulceration;
      parasites have not been identified in other organs. Two small cetaceans, a
      bottlenose dolphin Tursiops truncatus and a harbour porpoise Phocoena phocoena,
      presented marked gastric A. simplex infection, as well as chronic granulomatous
      and ulcerative dermatitis with intralesional nematodes, bordered by epithelial
      hyperplasia. Nematodes in the skin of the bottlenose dolphin were morphologically
      similar to Anisakis spp. Morphology of the parasitic remnants in the skin lesion
      of the harbour porpoise was indistinct, but molecular identification confirmed
      the presence of A. simplex. This is the first report of Anisakis spp. infection
      in the skin of marine mammals. 

PMID- 25590782
TI  - Properties of bacterial laccases and their application in bioremediation of
      industrial wastes.
AB  - The bioremediation process of industrial waste can be made more efficient using
      ligninolytic laccase enzymes, which are obtained from fungi, bacteria, higher
      plants, insects, and also in lichen. Laccase are catalyzed in the mono-electronic
      oxidation of a substrate from the expenditure of molecular oxygen. This enzyme
      belongs to the multicopper oxidases and participates in the cross linking of
      monomers, involved in the degradation of wide range industrial pollutants. In
      recent years, these enzymes have gained application in pulp and paper, textile
      and food industries. There are numerous reviews on laccases; however, a lot of
      information is still unknown due to their broad range of functions and
      applications. In this review, the bacterial laccases are focused for the
      bioremediation of various industrial pollutants. A brief description on
      structural molecular and physicochemical properties has been made. Moreover, the
      mechanism by which the reaction is catalyzed, the physical basis of
      thermostability and enantioselectivity, which requires more attention from
      researchers, and applications of laccase in various fields of biotechnology are
      pointed out. 

PMID- 25590783
TI  - An update on the management of Budd-Chiari syndrome: the issues of timing and
      choice of treatment.
AB  - Because of the rarity of Budd-Chiari syndrome (BCS), the flow chart of management
      comes from expert opinion and is not evidence based. To report an update on the
      management of BCS. I performed a review on published papers on BCS in an attempt
      to speculate in particular on the timing and the choice of treatment. Some
      authors suggest that the management of BCS should follow a step-wise strategy.
      Anticoagulation and medical therapy should be the first-line treatment.
      Revascularization or transjugular intrahepatic portosystemic shunt should be
      performed in case of no response to medical therapy. Orthotopic liver transplant
      should be used as a rescue therapy. The biggest criticism of this flow chart is
      that it is based on the assumption that patients with BCS should receive further
      treatment only when hemodynamic effects on portal hypertension become clinically
      evident, thus paying little attention to the chronic ischemic liver damage
      effects on hepatic function and to the possibility of preventing liver failure by
      relieving impaired hepatic veins outflow. Recently, I presented a proposal of a
      new algorithm for the management of BCS, in which medical therapy alone is
      suggested only for patients without any sign of portal hypertension, irrespective
      of whether early interventional treatment is suggested when either any symptoms
      or signs of portal hypertension appear, with the aim of preventing hepatic
      fibrosis development, disease progression, and finally improving outcome. Given
      that the benefit of treatments for BCS is not under debate, guidelines for the
      management of BCS should be re-evaluated and updated, with particular attention
      to both the timing and the choice of treatment. 

PMID- 25590779
TI  - Active contractility at E-cadherin junctions and its implications for cell
      extrusion in cancer.
AB  - Cellular contractility regulates tissue cohesion and morphogenesis. In epithelia,
      E-cadherin adhesion couples the contractile cortices of neighboring cells
      together to produce tension at junctions that can be transmitted across the
      epithelium in a planar fashion. We have recently demonstrated that contractility
      is also patterned in the apical-lateral axis within epithelial junctions. Our
      findings highlight the role that cytoskeletal regulation plays in controlling the
      levels of intra-junctional tension. Of note, dysregulation of this apicolateral
      pattern of tension can drive oncogenic cell extrusion. In this article, we
      provide a detailed description of the actomyosin cytoskeleton organization during
      oncogenic extrusion and discuss the implications of cell extrusion in cancer. 

PMID- 25590784
TI  - Prasugrel and ticagrelor compared to clopidogrel in non-ST-segment elevation
      acute coronary syndromes undergoing percutaneous coronary interventions:
      Certainties and uncertainties.

PMID- 25590785
TI  - Plasmapheresis in cast nephropathy: yes or no?
AB  - PURPOSE OF REVIEW: Renal failure is a frequent complication of multiple myeloma
      and portends a poor prognosis. Plasmapheresis has been suggested as an adjunct to
      chemotherapy to halt or reverse renal injury associated with multiple myeloma.
      The purpose of this article is to review the rationale for using plasmapheresis
      for this indication and then provide a discussion of the evidence regarding its
      use. RECENT FINDINGS: The outcome of patients with multiple myeloma has improved
      considerably in recent years, mostly owing to the introduction of new highly
      effective chemotherapeutic agents. However, patients with renal failure who do
      not recover independent renal function continue to have very poor prognosis.
      Recent evidence now indicates that an early and sustained reduction in
      circulating free light chains (FLCs) is associated with improved renal recovery
      in patients with myeloma kidney. Extracorporeal removal of FLCs with
      plasmapheresis, or other techniques, can achieve rapid and sustained reduction in
      serum FLC concentration in patients with acute myeloma kidney. Unfortunately,
      there is currently no convincing evidence in the literature that the addition of
      mechanical removal of FLC to standard chemotherapy translates into clinical
      benefits for patients. SUMMARY: Plasmapheresis is theoretically attractive as a
      means of rapidly lowering serum FLC burden in the hope of reducing nephrotoxicity
      in patients with multiple myeloma. However, the role of plasmapheresis in
      improving renal prognosis and patient survival remains to be demonstrated.

PMID- 25590786
TI  - Regulating Greatwall for mitosis.

PMID- 25590787
TI  - Tuning Salmonella for cancer therapy.

PMID- 25590788
TI  - Mitochondrial and metabolic remodeling during reprogramming and differentiation
      of the reprogrammed cells.
AB  - Reprogramming is one of the most essential areas of research in stem cell
      biology. Despite this importance, the mechanism and correlates of reprogramming
      remain largely unknown. In this study, we investigated the cytoplasmic remodeling
      and changes in metabolism that occur during reprogramming and differentiation of
      pluripotent stem cells. Specifically, we examined the cellular organelles of
      three pluripotent stem cells, embryonic stem cells (ESCs), induced pluripotent
      stem cells (iPSCs), and epiblast stem cells (EpiSCs), by electron microscopy. We
      found that the cellular organelles of primed pluripotent EpiSCs were more similar
      to those of naive pluripotent ESCs and iPSCs than somatic cells. EpiSCs, as well
      as ESCs and iPSCs, contain large nuclei, poorly developed endoplasmic reticula,
      and underdeveloped cristae; however, their mitochondria were still mature
      relative to the mitochondria of ESCs and iPSCs. Next, we differentiated these
      pluripotent stem cells into neural stem cells (NSCs) in vitro and compared the
      morphology of organelles. We found that the morphology of organelles of NSCs
      differentiated from ESCs, iPSCs, and EpiSCs was indistinguishable from brain
      derived NSCs. Finally, we examined the changes in energy metabolism that
      accompanied mitochondrial remodeling during reprogramming and differentiation. We
      found that the glycolytic activity of ESCs and iPSCs was greater compared with
      EpiSCs, and that the glycolytic activity of EpiSCs was greater compared with NSCs
      differentiated from ESCs, iPSCs, and EpiSCs. These results suggest that a change
      in the cellular state is accompanied by dynamic changes in the morphology of
      cytoplasmic organelles and corresponding changes in energy metabolism. 

PMID- 25590789
TI  - 5-HT6 Receptor: A New Player Controlling the Development of Neural Circuits.
AB  - 5-HT6 receptor (5-HT6R) is a G protein-coupled receptor that has recently emerged
      as a new regulator of neural development. In addition to the canonical Gs
      adenylyl cyclase pathway, recent proteomics approaches reveal that 5-HT6R is able
      to engage key developmental signaling pathways controlling neuronal circuit
      formation, neuronal connectivity, and psychiatric-relevant behaviors. For
      example, at early stages of neuronal development, expression of 5-HT6R
      constitutively regulates the activity of the cyclin-dependent kinase (Cdk)5 and,
      through this mechanism, controls cellular processes involved in circuit
      formation, including neuronal migration and neurite outgrowth. In addition to the
      Cdk5 pathway, 5-HT6R modulates a variety of key developmental targets such as
      Fyn, Jab1, and mammalian target of rapamycin (mTOR). Engagement of developmental
      pathways through 5-HT6R pharmacological manipulation has led to interesting new
      therapeutic perspectives in the field of psychiatric-related disorders. Indeed, 5
      HT6R blockade can rescue a pathological overactivation of the mTOR pathway
      induced by early life insults in rodents and normalizes the associated social and
      episodic memory deficits. Here, we review recent evidence supporting the notion
      that 5-HT6R is at the interface of key developmental signaling pathways and a
      novel actor in the orchestration of neural circuit formation. 

PMID- 25590790
TI  - The reliability of the current perception threshold in volunteers and its
      applicability in a clinical setting.
AB  - BACKGROUND: Even though current perception threshold (CPT) has been used for
      evaluating the effectiveness of sensory block in patients before surgery, its
      reliability under controlled conditions has not been investigated. Two
      independent investigations were performed. The primary objective of the first
      study was to determine the test-retest reliability of CPT measures after repeated
      stimulations in a group of healthy volunteers. The primary objective of the
      second study was to evaluate the clinical applicability of this technique to
      assess the sensory onset of a femoral nerve block in patients undergoing knee
      surgery. METHODS: Thirty healthy subjects participated in 2 identical sessions,
      separated by at least 24 hours, in which CPTs were measured after 5 consecutive
      stimulations over the anteromedial aspect of the thigh. Similar measures were
      obtained in 15 orthopedic patients receiving a femoral nerve block with 20 mL of
      ropivacaine 0.5%. Test-retest reliability was assessed using intraclass
      correlation (ICC) and standard error of measurement (expressed as coefficient of
      variation [CV(SEM)]), whereas Student t test (P < 0.05) compared the increase in
      CPTs over baseline. RESULTS: Within-day ICC values ranged (% confidence interval
      [CI]) from 0.66 to 0.95 with a CV(SEM) of approximately 39% (% CI: 17%-58%).
      Between-day ICC values, ranging from 0.57 to 0.94 (CV(SEM): approximately 45%, %
      CI: 13%-71%), indicated that day-to-day CPT measurements are also variable. The
      current intensity needed for sensory perception in orthopedic patients
      significantly increased, varying from a mean CPT value of 82.5 +/- 66.5 MUA (SD)
      at time zero to an average of 481 +/- 338 MUA, 22 +/- 8 minutes after the
      administration of the local anesthetic. CONCLUSIONS: CPT proved to be a reliable
      assessment tool for within-day sensory perception in healthy volunteers. Our
      study also suggests that CPT can be applied to characterize, in a quantitative
      manner, the sensory onset of a peripheral nerve block in a clinical setting,
      thereby supporting its use in future studies comparing different regional
      anesthetic modalities or approaches.

PMID- 25590791
TI  - The Impact of Incident Postoperative Delirium on Survival of Elderly Patients
      After Surgery for Hip Fracture Repair.
AB  - BACKGROUND: The impact of delirium on survival of elderly patients remains
      undetermined with conflicting results from clinical studies and meta-analysis. In
      this study, we assessed the relationship between long-term mortality and incident
      postoperative delirium in elderly patients undergoing hip fracture repair.
      METHODS: Patients >=65 years old who were not delirious before undergoing hip
      fracture repair were included in a database maintained prospectively from March
      1999 to July 2009. All participating patients underwent delirium assessment on
      the second postoperative day by using the confusion assessment method. Survival
      of the participants was determined as of October 2012. RESULTS: In 459 patients,
      the mean (SD) period of evaluation from surgery until death or study closure was
      4.1 (3.5) years with patients followed for as long as 13.6 years. Preoperative
      cognitive impairment was present in 120 patients (26.1%), and delirium on the
      second postoperative day was observed in 151 (32.9%) of these patients. Although
      univariate analysis demonstrated a strong association between incident
      postoperative delirium and survival, this relationship did not persist in a
      multivariate model. Survival was a function of age at the time of surgery (P <
      0.001), illness severity as determined by the ASA physical status score (P <
      0.001), and duration of admission to the intensive care unit after surgery (P <
      0.001). Incorporation of incident postoperative delirium did not meaningfully (P
      = 0.22) enhance the final survival model. In such a model, the hazard ratio (95%
      confidence interval) for incident postoperative delirium was 1.25 (0.92-1.48).
      CONCLUSIONS: Incident postoperative delirium was not significantly associated
      with decreased survival in elderly patients undergoing hip fracture repair.

PMID- 25590792
TI  - Yogurt Containing the Probacteria Lactobacillus acidophilus Combined with Natural
      Antioxidants Mitigates Doxorubicin-Induced Cardiomyopathy in Rats.
AB  - Probiotics and antioxidants have a definite improving effect in cardiovascular
      diseases. This study aims at mitigating doxorubicin toxicity on cardiac function
      through consuming a functional food. Five groups of adult male Sprague-Dawley
      rats were used along 22 weeks. Group I received 30 g/kg/day food enriched with
      yogurt, green tea extract, and carrots (80, 0.84, and 100 g/kg diet,
      respectively) from the first week, group II received carvedilol 30 mg/kg/day
      orally from week 17, group III received both carvedilol and tested food, and
      groups IV and V were +ve and -ve control groups, respectively. In week 17,
      cardiomyopathy was induced by i.p. injection of 2.5 mg/kg doxorubicin every 48 h
      for 2 weeks. Histopathological and electrophysiological examinations and
      biochemical analysis were done. Lipid peroxidation, antioxidant effect, heart
      failure compensatory mediators, and proinflammatory cytokines were assessed.
      Tested food normalized time between the start of Q wave and the end of T wave on
      electrocardiogram (QT interval) and heart rate compared to the doxorubicin group
      (P<.05). It also improved hypertrophy indicated by a significant (P<.05) decrease
      in heart/body weight ratio, angiotensin-II (Ang-II), and atrial natriuretic
      peptide (ANP) serum levels. Histopathological examination of cardiac sections
      from the tested food group revealed less marked vacuolization and low
      perivascular fibrosis percentage (0.7803 +/- 0.04). A significant (P<.001)
      decrease in serum creatine kinase-membrane bound, lactate dehydrogenase,
      triglycerides, cholesterol, low-density lipoprotein cholesterol, and tissue
      malondialdehyde (MDA) levels was observed in addition to an increase in serum
      Na(+)/K(+) ATP1A1 and cardiac reduced glutathione (GSH) levels. Tested food also
      lowered the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) serum levels significantly (P<.01). Probiotic food
      containing Lactobacillus acidophilus, green tea, and carrots can improve membrane
      integrity and cardiac contractility in doxorubicin-induced cardiomyopathy by
      decreasing TNF-alpha, IL-6, MDA, increasing GSH, and modulating compensatory
      mediators such as Ang-II and ANP.

PMID- 25590793
TI  - Looking into Candida albicans infection, host response, and antifungal
      strategies.
AB  - Candida albicans, a commonly encountered fungal pathogen, causes diseases varying
      from superficial mucosal complaints to life-threatening systemic disorders. Among
      the virulence traits of C. albicans, yeast-to-hypha transition is most widely
      acknowledged. Host innate immunity to C. albicans critically requires pattern
      recognition receptors (PRRs), and defence against C. albicans infection is
      provided by an exquisite interplay between the innate and adaptive arms of the
      host immune system. 

PMID- 25590794
TI  - Antimicrobial and bacteria-releasing multifunctional surfaces: oligo (p-phenylene
      ethynylene)/poly (N-isopropylacrylamide) films deposited by RIR-MAPLE.
AB  - Antimicrobial oligo (p-phenylene-ethynylene) (OPE) films have previously been
      demonstrated to show effective ultraviolet A (UVA) light-induced biocidal
      activity; however, a serious problem arises from the accumulation of dead
      bacteria and debris on the films that limits their effectiveness and application.
      In this work, we address this challenge by incorporating thermally-responsive
      poly (N-isopropylacrylamide) (PNIPAAm), which provides on-demand bacteria
      releasing functionality. Multifunctional surfaces comprising blended films of OPE
      and PNIPAAm were deposited on substrates by resonant infrared, matrix-assisted
      pulsed laser evaporation (RIR-MAPLE) using a sequential co-deposition mode. In
      this way, RIR-MAPLE enabled the deposition of multifunctional films with surface
      properties and film functionality that can be tailored, precisely and
      systematically, by controlling the chemical composition of the deposited film.
      The surface properties of these films were characterized by UV-visible (UV-vis)
      absorbance spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force
      microscopy (AFM), and water contact angle measurements. The interactions between
      bacteria and the deposited films were tested using two model bacteria:
      Escherichia coli K12 (Gram-negative) and Staphylococcus epidermidis (Gram
      positive). The antimicrobial and bacteria-release properties of the blended films
      were controlled by varying the OPE/PNIPAAm ratio in the RIR-MAPLE emulsion
      target, providing an easy way to optimize the multifunctional surface. The
      OPE/PNIPAAm blended films with optimized composition killed a majority of
      attached E. coli bacteria at 37  degrees C and under UVA exposure, and the dead
      bacteria were then removed from the films simply by rinsing with water at 25 
      degrees C.

PMID- 25590796
TI  - Structures of [CoO(CO2)n]- and [NiO(CO2)n]- clusters studied by infrared
      spectroscopy.
AB  - We present infrared spectra of [CoO(CO2)n](-) and [NiO(CO2)n](-) clusters and
      interpret them in the framework of computational results employing density
      functional theory. We find that both [CoO(CO2)n](-) and [NiO(CO2)n](-) clusters
      are generally composed of the same core isomers. The dominant isomers consist of
      an eta(2) CO2 ligand and a CO3 moiety that can be bound to the metal atom with
      monodentate (eta(1)) or bidentate (eta(2)) connectivity. Minor structural isomers
      observed are composed of a C2O4 moiety with a lone oxygen atom or a CO3 unit. 

PMID- 25590795
TI  - Genetic and environmental factors in conjunctival UV autofluorescence.
AB  - IMPORTANCE: Conjunctival UV autofluorescence (CUVAF) photography was developed to
      detect and characterize preclinical sunlight-induced ocular damage. Ocular sun
      exposure has been related to cases of pterygia and was recently negatively
      correlated with myopia. Hence, CUVAF has excellent potential as an objective
      biomarker of sun exposure. However, much variation in CUVAF has been observed,
      and the relative contributions of genes and environment to this variation have
      not yet been identified. OBJECTIVE: To investigate sources of variation in CUVAF
      in relation to its potential clinical relevance. DESIGN, SETTING, AND
      PARTICIPANTS: We performed a cross-sectional analysis of 3 population-based
      cohort studies in the general community, including the Twins Eye Study in
      Tasmania, the Brisbane Adolescent Twin Study, and the Western Australian
      Pregnancy Cohort (Raine) Study. The twin studies were conducted between 2001 and
      2009, and the 20-year follow-up of the Raine Study was completed between March
      2010 and February 2012. We included genotypic and phenotypic data from 295
      Australian families in the Tasmanian and Brisbane twin studies and from 661
      participants in the 20-year follow-up of the Raine Study. We compared CUVAF
      levels in the 3 cohorts and performed a classic twin study to partition variation
      in CUVAF. We also conducted a genome-wide association analysis to identify
      specific genetic variants associated with CUVAF. MAIN OUTCOMES AND MEASURES: The
      total area of CUVAF, heritability of CUVAF, and single-nucleotide polymorphisms
      (SNPs) associated with CUVAF from the genome-wide association study. RESULTS:
      Within twin cohorts, individuals living closer to the equator (latitude, 27.47
      degrees  S) had higher levels of CUVAF compared with individuals from southern
      regions (latitude, 42.88 degrees  S) (median [interquartile range], 45.4 [26.8
      68.5] vs 28.7 [15.0-42.3] mm2; P < .001). The variation in CUVAF explained by the
      additive genetic component was 0.37 (95% CI, 0.22-0.56), whereas the variation
      due to the common environment was 0.50 (95% CI; 0.29-0.71). The SNP rs1060043,
      located approximately 800 base pairs away from the SLC1A5 gene, a member of the
      solute carrier family 1, had a genome-wide significant association with a P value
      of 3.2 * 10-8. Gene-based analysis did not improve our power to detect
      association with other genes. CONCLUSIONS AND RELEVANCE: Our findings confirm
      that, although a large environmental component to CUVAF (equivalent of sun
      exposure) exists, genes also play a significant role. We identified a SNP
      (rs1060043) as being significantly associated with CUVAF; replication of this
      finding in future studies is warranted.

PMID- 25590797
TI  - A rapidly enlarging maxillary lesion. Left maxillary giant cell reparative
      granuloma (GCRG).

PMID- 25590799
TI  - Germ cell-specific Atg7 knockout results in primary ovarian insufficiency in
      female mice.
AB  - Primary ovarian insufficiency (POI) is a common cause of infertility in around 1
      2% of women aged <40 years. However, the mechanisms that cause POI are still
      poorly understood. Here we showed that germ cell-specific knockout of an
      essential autophagy induction gene Atg7 led to subfertility in female mice. The
      subfertility of Atg7 deletion females was caused by severe ovarian follicle loss,
      which is very similar to human POI patients. Further investigation revealed that
      germ cell-specific Atg7 knockout resulted in germ cell over-loss at the neonatal
      transition period. In addition, our in vitro studies also demonstrated that
      autophagy could protect oocytes from over-loss by apoptosis in neonatal ovaries
      under the starvation condition. Taken together, our results uncover a new role
      for autophagy in the regulation of ovarian primordial follicle reservation and
      hint that autophagy-related genes might be potential pathogenic genes to POI of
      women. 

PMID- 25590798
TI  - Interplay between ROS and autophagy in cancer cells, from tumor initiation to
      cancer therapy.
AB  - Cancer formation is a complex and highly regulated multi-step process which is
      highly dependent of its environment, from the tissue to the patient. This
      complexity implies the development of specific treatments adapted to each type of
      tumor. The initial step of cancer formation requires the transformation of a
      healthy cell to a cancer cell, a process regulated by multiple intracellular and
      extracellular stimuli. The further steps, from the anarchic proliferation of
      cancer cells to form a primary tumor to the migration of cancer cells to distant
      organs to form metastasis, are also highly dependent of the tumor environment but
      of intracellular molecules and pathways as well. In this review, we will focus on
      the regulatory role of reactive oxygen species (ROS) and autophagy levels during
      the course of cancer development, from cellular transformation to the formation
      of metastasis. These data will allow us to discuss the potential of this molecule
      or pathway as putative future therapeutic targets. 

PMID- 25590800
TI  - Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer
      cell killing activity as single agents and in combination with ABT-263
      (navitoclax).
AB  - The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a
      known resistance factor for small-molecule BCL-2 family inhibitors such as ABT
      263 (navitoclax), making it an attractive therapeutic target. However, directly
      inhibiting this target requires the disruption of high-affinity protein-protein
      interactions, and therefore designing small molecules potent enough to inhibit
      MCL-1 in cells has proven extremely challenging. Here, we describe a series of
      indole-2-carboxylic acids, exemplified by the compound A-1210477, that bind to
      MCL-1 selectively and with sufficient affinity to disrupt MCL-1-BIM complexes in
      living cells. A-1210477 induces the hallmarks of intrinsic apoptosis and
      demonstrates single agent killing of multiple myeloma and non-small cell lung
      cancer cell lines demonstrated to be MCL-1 dependent by BH3 profiling or siRNA
      rescue experiments. As predicted, A-1210477 synergizes with the BCL-2/BCL-XL
      inhibitor navitoclax to kill a variety of cancer cell lines. This work represents
      the first description of small-molecule MCL-1 inhibitors with sufficient potency
      to induce clear on-target cellular activity. It also demonstrates the utility of
      these molecules as chemical tools for dissecting the basic biology of MCL-1 and
      the promise of small-molecule MCL-1 inhibitors as potential therapeutics for the
      treatment of cancer. 

PMID- 25590801
TI  - Phosphorylation of the translation initiation factor eIF2alpha at serine 51
      determines the cell fate decisions of Akt in response to oxidative stress.
AB  - Phosphorylation of the alpha subunit of the translation initiation factor eIF2 at
      serine 51 (eIF2alphaP) is a master regulator of cell adaptation to various forms
      of stress with implications in antitumor treatments with chemotherapeutic drugs.
      Herein, we demonstrate that genetic loss of the eIF2alpha kinases PERK and GCN2
      or impaired eIF2alphaP by genetic means renders immortalized mouse fibroblasts as
      well as human tumor cells increasingly susceptible to death by oxidative stress.
      We also show that eIF2alphaP facilitates Akt activation in cells subjected to
      oxidative insults. However, whereas Akt activation has a pro-survival role in
      eIF2alphaP-proficient cells, the lesser amount of activated Akt in eIF2alphaP
      deficient cells promotes death. At the molecular level, we demonstrate that
      eIF2alphaP acts through an ATF4-independent mechanism to control Akt activity via
      the regulation of mTORC1. Specifically, eIF2alphaP downregulates mTORC1 activity,
      which in turn relieves the feedback inhibition of PI3K resulting in the
      upregulation of the mTORC2-Akt arm. Inhibition of mTORC1 by rapamycin restores
      Akt activity in eIF2alphaP-deficient cells but renders them highly susceptible to
      Akt-mediated death by oxidative stress. Our data demonstrate that eIF2alphaP acts
      as a molecular switch that dictates either cell survival or death by activated
      Akt in response to oxidative stress. Hence, we propose that inactivation of
      eIF2alphaP may be a suitable approach to unleash the killing power of Akt in
      tumor cells treated with pro-oxidant drugs. 

PMID- 25590802
TI  - Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling.
AB  - Pancreatic ductal adenocarcinoma (PDA) is a critical health issue in the field of
      cancer, with few therapeutic options. Evidence supports an implication of the
      intratumoral microenvironment (stroma) on PDA progression. However, its
      contribution to the role of neuroplastic changes within the pathophysiology and
      clinical course of PDA, through tumor recurrence and neuropathic pain, remains
      unknown, neglecting a putative, therapeutic window. Here, we report that the
      intratumoral microenvironment is a mediator of PDA-associated neural remodeling
      (PANR), and we highlight factors such as 'SLIT2' (an axon guidance molecule),
      which is expressed by cancer-associated fibroblasts (CAFs), that impact on
      neuroplastic changes in human PDA. We showed that 'CAF-secreted SLIT2' increases
      neurite outgrowth from dorsal root ganglia neurons as well as from Schwann cell
      migration/proliferation by modulating N-cadherin/beta-catenin signaling.
      Importantly, SLIT2/ROBO signaling inhibition disrupts this stromal/neural
      connection. Finally, we revealed that SLIT2 expression and CAFs are correlated
      with neural remodeling within human and mouse PDA. All together, our data
      demonstrate the implication of CAFs, through the secretion of axon guidance
      molecule, in PANR. Furthermore, it provides rationale to investigate the
      disruption of the stromal/neural compartment connection with SLIT2/ROBO
      inhibitors for the treatment of pancreatic cancer recurrence and pain. 

PMID- 25590803
TI  - MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be
      overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies.
AB  - Overexpression of anti-apoptotic BCL-2 family members is a hallmark of many
      lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and non
      Hodgkin lymphoma (NHL) that can be targeted with small molecule inhibitors. ABT
      199 is a rationally designed BCL-2 homology (BH)-3 mimetic that specifically
      binds to BCL-2, but not to MCL-1 and BCL-xL. Although the thrombocytopenia that
      occurs with navitoclax treatment has not been a problem with ABT-199, clinical
      trials in CLL could benefit by lowering the ABT-199 concentration through
      targeting other survival pathways. In this study, we investigated the mechanisms
      of resistance that develops to ABT-199 therapy by generating ABT-199-resistant
      (ABT199-R) cell lines via chronic exposure of NHL cell lines to ABT-199. Acquired
      resistance resulted in substantial AKT activation and upregulation of MCL-1 and
      BCL-xL levels that sequestered BIM. ABT199-R cells exhibited increased MCL-1
      stability and failed to activate BAX in response to ABT-199. The ABT-199 acquired
      and inherent resistant cells were sensitized to treatment with ABT-199 by
      inhibitors of the PI3K, AKT, and mTOR pathways, NVP-BEZ235 and GS-1101. NVP
      BEZ235, a dual inhibitor of p-AKT and mTOR, reduced MCL-1 levels causing BIM
      release from MCL-1 and BCL-xL, thus leading to cell death by BAX activation. The
      PI3Kdelta inhibitor GS-1101 (idelalisib) downregulated MCL-1 and sensitized
      ABT199-R cells through AKT-mediated BAX activation. A genetic approach, through
      siRNA-mediated down-regulation of AKT, MCL-1, and BCL-xL, significantly decreased
      cell survival, demonstrating the importance of these cell survival factors for
      ABT-199 resistance. Our findings suggest a novel mechanism that modulates the
      expression and activity of pro-survival proteins to confer treatment resistance
      that could be exploited by a rational combination therapeutic regimen that could
      be effective for treating lymphoid malignancies. 

PMID- 25590804
TI  - PKR downregulation prevents neurodegeneration and beta-amyloid production in a
      thiamine-deficient model.
AB  - Brain thiamine homeostasis has an important role in energy metabolism and
      displays reduced activity in Alzheimer's disease (AD). Thiamine deficiency (TD)
      induces regionally specific neuronal death in the animal and human brains
      associated with a mild chronic impairment of oxidative metabolism. These features
      make the TD model amenable to investigate the cellular mechanisms of
      neurodegeneration. Once activated by various cellular stresses, including
      oxidative stress, PKR acts as a pro-apoptotic kinase and negatively controls the
      protein translation leading to an increase of BACE1 translation. In this study,
      we used a mouse TD model to assess the involvement of PKR in neuronal death and
      the molecular mechanisms of AD. Our results showed that the TD model activates
      the PKR-eIF2alpha pathway, increases the BACE1 expression levels of Abeta in
      specific thalamus nuclei and induces motor deficits and neurodegeneration. These
      effects are reversed by PKR downregulation (using a specific inhibitor or in PKR
      knockout mice). 

PMID- 25590805
TI  - Targeting heat-shock protein 90 with ganetespib for molecularly targeted therapy
      of gastric cancer.
AB  - Gastric cancer (GC) remains the fifth most common cancer worldwide. Heat-shock
      protein 90 (HSP90) has become an attractive therapeutic target in treating
      cancers, because of its abnormally high expression in cancers. Several successful
      cases of HSP90 inhibitors capable of inhibiting GC inspired us to try ganetespib,
      a clinically promising and actively investigated second-generation HSP90
      inhibitor in GC treatment. In our study, we show that ganetespib markedly reduced
      the growth of MGC-803 and also significantly inhibited the growth of SGC-7901 and
      MKN-28 in a dose-dependent manner. It induced G2/M cell-cycle arrest and
      apoptosis in all three cell lines, together with the related markers affected
      significantly. Mechanistically, ganetespib caused pronounced decrease of
      expression of classic HSP90 client proteins. Specifically, it greatly affected
      epidermal growth factor receptor (EGFR) signaling cascades by markedly decreasing
      the levels of total EGFR and EGFR on cell membranes. EGFR knockdown also induced
      cell-cycle arrest and apoptosis accompanied with a decrease of several EGFR
      downstream proteins. These results strongly support that EGFR signaling greatly
      contributes to the ganetespib inhibitory effects. Besides, we found that the
      responses of GC cell lines to ganetespib correlated well with their EGFR
      expression levels: MGC-803, as well as AGS and BGC-803, with higher EGFR
      expression responded to ganetespib better, whereas SGC-7901 and MKN-28 with lower
      EGFR levels were much less sensitive to ganetespib. Although SGC-7901 and MKN-28
      were not very sensitive to ganetespib, ganetespib worked synergistically with
      radiation and cisplatin in killing them. Importantly, ganetespib significantly
      inhibited the growth of xenograft tumors in vivo as a single agent or in
      combination with cisplatin. Results of hematoxylin/eosin staining, TUNEL
      (terminal deoxynucleotidyl transferase dUTP nick-end labeling) assays, and
      immunohistochemistry staining of phosphorylated cyclin-dependent kinase 1
      (pCDK1), EGFR and Ki-67 revealed significant differences in ganetespib-treated
      tumors. Collectively, our data suggest that ganetespib, as a new potent treatment
      option, can be used for the molecularly targeted therapy of GC patients according
      to their expression profiles of EGFR. 

PMID- 25590806
TI  - Dose-dependent effects of selenite (Se(4+)) on arsenite (As(3+))-induced
      apoptosis and differentiation in acute promyelocytic leukemia cells.
AB  - To enhance the therapeutic effects and decrease the adverse effects of arsenic on
      the treatment of acute promyelocytic leukemia, we investigated the co-effects of
      selenite (Se(4+)) and arsenite (As(3+)) on the apoptosis and differentiation of
      NB4 cells and primary APL cells. A 1.0-MUM concentration of Se(4+) prevented the
      cells from undergoing As(3+)-induced apoptosis by inhibiting As(3+) uptake,
      eliminating As(3+)-generated reactive oxygen species, and repressing the
      mitochondria-mediated intrinsic apoptosis pathway. However, 4.0 MUM Se(4+)
      exerted synergistic effects with As(3+) on cell apoptosis by promoting As(3+)
      uptake, downregulating nuclear factor-kB, and activating caspase-3. In addition
      to apoptosis, 1.0 and 3.2 MUM Se(4+) showed contrasting effects on As(3+)-induced
      differentiation in NB4 cells and primary APL cells. The 3.2 MUM Se(4+) enhanced
      As(3+)-induced differentiation by promoting the degradation of promyelocytic
      leukemia protein-retinoic acid receptor-alpha (PML-RARalpha) oncoprotein, but 1.0
      MUM Se(4+) did not have this effect. Based on mechanistic studies, Se(4+), which
      is similar to As(3+), might bind directly to Zn(2+)-binding sites of the PML RING
      domain, thus controlling the fate of PML-RARalpha oncoprotein. 

PMID- 25590807
TI  - Macrophage peroxisome proliferator-activated receptor gamma deficiency delays
      skin wound healing through impairing apoptotic cell clearance in mice.
AB  - Skin wound macrophages are key regulators of skin repair and their dysfunction
      causes chronic, non-healing skin wounds. Peroxisome proliferator-activated
      receptor gamma (PPARgamma) regulates pleiotropic functions of macrophages, but
      its contribution in skin wound healing is poorly defined. We observed that
      macrophage PPARgamma expression was upregulated during skin wound healing.
      Furthermore, macrophage PPARgamma deficiency (PPARgamma-knock out (KO)) mice
      exhibited impaired skin wound healing with reduced collagen deposition,
      angiogenesis and granulation formation. The tumor necrosis factor alpha (TNF
      alpha) expression in wounds of PPARgamma-KO mice was significantly increased and
      local restoration of TNF-alpha reversed the healing deficit in PPARgamma-KO mice.
      Wound macrophages produced higher levels of TNF-alpha in PPARgamma-KO mice
      compared with control. In vitro, the higher production of TNF-alpha by PPARgamma
      KO macrophages was associated with impaired apoptotic cell clearance.
      Correspondingly, increased apoptotic cell accumulation was found in skin wound of
      PPARgamma-KO mice. Mechanically, peritoneal and skin wound macrophages expressed
      lower levels of various phagocytosis-related molecules. In addition, PPARgamma
      agonist accelerated wound healing and reduced local TNF-alpha expression and
      wound apoptotic cells accumulation in wild type but not PPARgamma-KO mice.
      Therefore, PPARgamma has a pivotal role in controlling wound macrophage clearance
      of apoptotic cells to ensure efficient skin wound healing, suggesting a potential
      new therapeutic target for skin wound healing. 

PMID- 25590808
TI  - Glutathione transferases P1/P2 regulate the timing of signaling pathway
      activations and cell cycle progression during mouse liver regeneration.
AB  - Glutathione transferases (GST) are phase II enzymes catalyzing the detoxification
      of endogenous noxious compounds and xenobiotics. They also regulate
      phosphorylation activities of MAPKinases in a catalytic-independent manner.
      Previous studies have demonstrated the regulation of JNK-dependent pathway by
      GSTP1/2. Considering the crucial role of JNK in the early steps of the hepatocyte
      cell cycle, we sought to determine whether GSTP1/2 were essential for hepatocyte
      proliferation following partial hepatectomy (PH). Using a conventional double
      knockout mouse model for the Gstp1 and Gstp2 genes, we found that the lack of
      GSTP1/P2 reduced the rate of DNA replication and mitotic index during the first
      wave of hepatocyte proliferation. The lowered proliferation was associated with
      the decrease in TNFalpha and IL-6 plasma concentrations, reduced hepatic HGF
      expression and delayed and/or altered activation of STAT3, JNK and ERK1/2
      signaling pathways. In addition, the expression and/or activation of cell cycle
      regulators such as Cyclin D1, CDK4, E2F1 and MCM7 was postponed demonstrating
      that the absence of GSTP1/2 delayed the entry into and progression through the G1
      phase of the cell cycle and impaired the synchrony of proliferation in
      hepatocytes following PH. Furthermore, while JNK and its downstream targets c-Jun
      and ATF2 were activated during the early steps of the liver regeneration in wild
      type animals, the constitutively active JNK found in the quiescent liver of
      Gstp1/2 knockout mice underwent a decrease in its activity after PH. Transient
      induction of antioxidant enzymes and nitric oxide synthase were also delayed or
      repressed during the regenerative response. Altogether our results demonstrate
      that GSTP1/2 are a critical regulators of hepatocyte proliferation in the initial
      phases of liver regeneration. 

PMID- 25590809
TI  - NAMPT inhibition sensitizes pancreatic adenocarcinoma cells to tumor-selective,
      PAR-independent metabolic catastrophe and cell death induced by beta-lapachone.
AB  - Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors (e.g., FK866) target
      the most active pathway of NAD(+) synthesis in tumor cells, but lack tumor
      selectivity for use as a single agent. Reducing NAD(+) pools by inhibiting NAMPT
      primed pancreatic ductal adenocarcinoma (PDA) cells for poly(ADP ribose)
      polymerase (PARP1)-dependent cell death induced by the targeted cancer
      therapeutic, beta-lapachone (beta-lap, ARQ761), independent of poly(ADP ribose)
      (PAR) accumulation. beta-Lap is bioactivated by NADPH:quinone oxidoreductase 1
      (NQO1) in a futile redox cycle that consumes oxygen and generates high levels of
      reactive oxygen species (ROS) that cause extensive DNA damage and rapid PARP1
      mediated NAD(+) consumption. Synergy with FK866+beta-lap was tumor-selective,
      only occurring in NQO1-overexpressing cancer cells, which is noted in a majority
      (~85%) of PDA cases. This treatment strategy simultaneously decreases NAD(+)
      synthesis while increasing NAD(+) consumption, reducing required doses and
      treatment times for both drugs and increasing potency. These complementary
      mechanisms caused profound NAD(P)(+) depletion and inhibited glycolysis, driving
      down adenosine triphosphate levels and preventing recovery normally observed with
      either agent alone. Cancer cells died through an ROS-induced, MU-calpain-mediated
      programmed cell death process that kills independent of caspase activation and is
      not driven by PAR accumulation, which we call NAD(+)-Keresis. Non-overlapping
      specificities of FK866 for PDA tumors that rely heavily on NAMPT-catalyzed NAD(+)
      synthesis and beta-lap for cancer cells with elevated NQO1 levels affords high
      tumor-selectivity. The concept of reducing NAD(+) pools in cancer cells to
      sensitize them to ROS-mediated cell death by beta-lap is a novel strategy with
      potential application for pancreatic and other types of NQO1+ solid tumors. 

PMID- 25590810
TI  - The role of hypoxia-inducible factor-2 in digestive system cancers.
AB  - Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia
      inducible factors (HIFs), HIF-1alpha and HIF-2alpha, primarily mediate the
      transcriptional response to hypoxia. Despite the high homology between HIF-1alpha
      and HIF-2alpha, emerging evidence suggests differences between both molecules in
      terms of transcriptional targets as well as impact on multiple physiological
      pathways and tumorigenesis. To date, much progress has been made toward
      understanding the roles of HIF-2alpha in digestive system cancers. Indeed, HIF
      2alpha has been shown to regulate multiple aspects of digestive system cancers,
      including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis
      and resistance to chemotherapy. These findings make HIF-2alpha a critical
      regulator of this malignant phenotype. Here we summarize the function of HIF-2
      during cancer development as well as its contribution to tumorigenesis in
      digestive system malignancies. 

PMID- 25590811
TI  - Reactive oxygen species-mediated therapeutic response and resistance in
      glioblastoma.
AB  - Glioblastoma (GBM) resistance to therapy is the most common cause of tumor
      recurrence, which is ultimately fatal in 90% of the patients 5 years after
      initial diagnosis. A sub-population of tumor cells with stem-like properties,
      glioma stem cells (GSCs), is specifically endowed to resist or adapt to the
      standard therapies, leading to therapeutic resistance. Several anticancer agents,
      collectively termed redox therapeutics, act by increasing intracellular levels of
      reactive oxygen species (ROS). In this study, we investigated mechanisms
      underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non
      psychoactive cannabinoid and redox modulator. Using primary GSCs, we showed that
      CBD induced a robust increase in ROS, which led to the inhibition of cell
      survival, phosphorylated (p)-AKT, self-renewal and a significant increase in the
      survival of GSC-bearing mice. Inhibition of self-renewal was mediated by the
      activation of the p-p38 pathway and downregulation of key stem cell regulators
      Sox2, Id1 and p-STAT3. Following CBD treatment, a subset of GSC successfully
      adapted, leading to tumor regrowth. Microarray, Taqman and functional assays
      revealed that therapeutic resistance was mediated by enhanced expression of the
      antioxidant response system Xc catalytic subunit xCT (SLC7A11 (solute carrier
      family 7 (anionic amino-acid transporter light chain), member 11)) and ROS
      dependent upregulation of mesenchymal (MES) markers with concomitant
      downregulation of proneural (PN) markers, also known as PN-MES transition. This
      'reprogramming' of GSCs occurred in culture and in vivo and was partially due to
      activation of the NFE2L2 (NRF2 (nuclear factor, erythroid 2-like))
      transcriptional network. Using genetic knockdown and pharmacological inhibitors
      of SLC7A11, we demonstrated that combining CBD treatment with the inhibition of
      system Xc resulted in synergistic ROS increase leading to robust antitumor
      effects, that is, decreased GSC survival, self-renewal, and invasion. Our
      investigation provides novel mechanistic insights into the antitumor activity of
      redox therapeutics and suggests that combinatorial approaches using small
      molecule modulators of ROS offer therapeutic benefits in GBM. 

PMID- 25590815
TI  - Two high-pressure phases of SiS2 as missing links between the extremes of only
      edge-sharing and only corner-sharing tetrahedra.
AB  - The ambient pressure phase of silicon disulfide (NP-SiS2), published in 1935, is
      orthorhombic and contains chains of distorted, edge-sharing SiS4 tetrahedra. The
      first high pressure phase, HP3-SiS2, published in 1965 and quenchable to ambient
      conditions, is tetragonal and contains distorted corner-sharing SiS4 tetrahedra.
      Here, we report on the crystal structures of two monoclinic phases, HP1-SiS2 and
      HP2-SiS2, which can be considered as missing links between the orthorhombic and
      the tetragonal phase. Both monoclinic phases contain edge- as well as corner
      sharing SiS4 tetrahedra. With increasing pressure, the volume contraction (
      DeltaV/V) and the density, compared to the orthorhombic NP-phase, increase from
      only edge-sharing tetrahedra to only corner-sharing tetrahedra. The lattice and
      the positional parameters of NP-SiS2, HP1-SiS2, HP2-SiS2, and HP3-SiS2 were
      derived in good agreement with the experimental data from group-subgroup
      relationships with the CaF2 structure as aristotype. In addition, the Raman
      spectra of SiS2 show that the most intense bands of the new phases HP1-SiS2 and
      HP2-SiS2 (408 and 404 cm(-1), respectively) lie between those of NP-SiS2 (434 cm(
      1)) and HP3-SiS2 (324 cm(-1)). Density functional theory (DFT) calculations
      confirm these observations. 

PMID- 25590813
TI  - Structure-activity relationship for the oxadiazole class of antibiotics.
AB  - The structure-activity relationship (SAR) for the newly discovered oxadiazole
      class of antibiotics is described with evaluation of 120 derivatives of the lead
      structure. This class of antibiotics was discovered by in silico docking and
      scoring against the crystal structure of a penicillin-binding protein. They
      impair cell-wall biosynthesis and exhibit activities against the Gram-positive
      bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA)
      and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3
      (4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was
      efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a
      high volume of distribution, and low clearance. This antibiotic is bactericidal
      and is orally bioavailable in mice. This class of antibiotics holds great promise
      in recourse against infections by MRSA. 

PMID- 25590814
TI  - CaMKKbeta-AMPKalpha2 signaling contributes to mitotic Golgi fragmentation and the
      G2/M transition in mammalian cells.
AB  - Before a cell enters mitosis, the Golgi apparatus undergoes extensive
      fragmentation. This is required for the correct partitioning of the Golgi
      apparatus into daughter cells, and inhibition of this process leads to cell cycle
      arrest in G2 phase. AMP-activated protein kinase (AMPK) plays critical roles in
      regulating growth and reprogramming metabolism. Recent studies have suggested
      that AMPK promotes mitotic progression and Golgi disassembly, and that this seems
      independent of the cellular energy status. However, the molecular mechanism
      underlying these events is not well understood. Here, we show that both treatment
      with compound C and depletion of AMPKalpha2 (but not AMPKalpha1) delays the G2/M
      transition in synchronized HeLa cells, as evidenced by flow cytometry and mitotic
      index analysis. Furthermore, knockdown of AMPKalpha2 specifically delays further
      fragmentation of isolated Golgi stacks. Interestingly, pAMPKalpha(Thr172) signals
      transiently appear in the perinuclear region of late G2/early prophase cells,
      partially co-localizing with the Golgi matrix protein, GM-130. These Golgi
      pAMPKalpha(Thr172) signals were also specifically abolished by AMPKalpha2
      knockdown, indicating specific spatio-temporal activation of AMPKalpha2 at Golgi
      complex during late G2/early prophases. We also found that the specific CaMKKbeta
      inhibitor, STO-609, reduces the pAMPKalpha (Thr172) signals in the perinuclear
      region of G2 phase cells and delays mitotic Golgi fragmentation. Taken together,
      these data suggest that AMPKalpha2 is the major catalytic subunit of AMPKalpha
      which regulates Golgi fragmentation and G2/M transition, and that the CaMKKbeta
      activates AMPKalpha2 during late G2 phase. 

PMID- 25590812
TI  - Blue journal conference. Aging and susceptibility to lung disease.
AB  - The aging of the population in the United States and throughout the developed
      world has increased morbidity and mortality attributable to lung disease, while
      the morbidity and mortality from other prevalent diseases has declined or
      remained stable. Recognizing the importance of aging in the development of lung
      disease, the American Thoracic Society (ATS) highlighted this topic as a core
      theme for the 2014 annual meeting. The relationship between aging and lung
      disease was discussed in several oral symposiums and poster sessions at the
      annual ATS meeting. In this article, we used the input gathered at the conference
      to develop a broad framework and perspective to stimulate basic, clinical, and
      translational research to understand how the aging process contributes to the
      onset and/or progression of lung diseases. A consistent theme that emerged from
      the conference was the need to apply novel, systems-based approaches to integrate
      a growing body of genomic, epigenomic, transcriptomic, and proteomic data and
      elucidate the relationship between biologic hallmarks of aging, altered lung
      function, and increased susceptibility to lung diseases in the older population.
      The challenge remains to causally link the molecular and cellular changes of
      aging with age-related changes in lung physiology and disease susceptibility. The
      purpose of this review is to stimulate further research to identify new
      strategies to prevent or treat age-related lung disease. 

PMID- 25590816
TI  - Highly sensitive and selective H2 sensing by ZnO nanofibers and the underlying
      sensing mechanism.
AB  - We report, and propose a mechanism for, the exceptional hydrogen gas (H2) sensing
      ability of ZnO nanofibers. In comparison to SnO2 nanofibers, ZnO nanofibers show
      outstanding H2 gas response and unmistakable H2 selectivity. Different from the
      reducing gas effect observed in SnO2 nanofibers, a semiconductor-to-metal
      transition that occurs in the presence of H2 gas molecules is responsible for the
      exceptional response and selectivity of ZnO nanofibers to H2. Notably, the
      presence of nanograins within nanofibers further intensifies the resistance
      modulation observed due to this transition. 

PMID- 25590817
TI  - Effect of dissolved humic acid on the Pb bioavailability in soil solution and its
      consequence on ecological risk.
AB  - Current risk characterization in ecological risk assessment does not consider
      bioavailability of heavy metals, which highly depends on physicochemical
      properties of environmental media. This study was set to investigate the effect
      of humic acid (HA), used as a surrogate of organic matter, on Pb toxicity and the
      subsequent effect on risk characterization in ecological risk assessment. Pb
      toxicity was assessed using Microtox((r)) in the presence and absence of two
      different forms of HA, particulate HA (pHA) and dissolved HA (dHA). With
      increasing contact time, the EC10 values increased (i.e., the toxic effects
      decreased) and the dissolved Pb concentrations of the filtrates decreased. The
      high correlation (R = 0.88, p < 0.001) between toxic effects determined using
      both the mixture and its filtrate as exposure media leads us to conclude that the
      Pb toxicity highly depends on the soluble fraction. Also, reduced Pb toxicity
      with increasing dHA concentrations, probably due to formation of Pb-dHA
      complexes, indicated that Pb toxicity largely comes from free Pb ions. Overall,
      this study shows the effect of HA on metal toxicity alleviation, and emphasizes
      the need for incorporating the bioavailable heavy metal concentrations in
      environmental media as a point of exposure in ecological risk assessment.

PMID- 25590818
TI  - Preparation of clinker from paper pulp industry wastes.
AB  - The production of paper pulp by the Kraft method generates considerable amounts
      of wastes. Namely, lime mud generated in the recovery circuit of chemical
      reagents, biological sludge from the wastewater treatment of wood digestion
      process and fly ash collected in the fluidized bed combustor used to generate
      electricity from biomass burning. The final destination of such wastes is an
      important concern, since environmental regulations are becoming stricter
      regarding their landfill. Driven by this fact, industries are looking for more
      sustainable solutions, such as the recycling in distinct products. This work
      tested these wastes as secondary raw materials to produce clinker/cement that was
      then experienced in mortar formulations. The first step involved the residues
      detailed characterization and a generated amounts survey. Then, specific but
      simple steps were suggested, aiming to facilitate transport and manipulation.
      Distinct blends were prepared and fired in order to get belitic and Portland
      clinkers. The Portland clinkers were processed at lower temperatures than the
      normally used in the industry due to the presence of mineralizing impurities in
      some wastes. Belite-based cements were used to produce mortars that developed
      satisfactory mechanical strength and did not reveal signs of deterioration or
      durability weaknesses. 

PMID- 25590819
TI  - Mature landfill leachate treatment by coagulation/flocculation combined with
      Fenton and solar photo-Fenton processes.
AB  - This work reports the treatment of a mature landfill leachate through the
      application of chemical-based treatment processes in order to achieve the
      discharge legal limits into natural water courses. Firstly, the effect of
      coagulation/flocculation with different chemicals was studied, evaluating the
      role of different initial pH and chemicals concentration. Afterwards, the
      efficiency of two different advanced oxidation processes for leachate remediation
      was assessed. Fenton and solar photo-Fenton processes were applied alone and in
      combination with a coagulation/flocculation pre-treatment. This physicochemical
      conditioning step, with 2 g L(-1) of FeCl3 . 6H2O at pH 5, allowed removing 63%
      of COD, 80% of turbidity and 74% of total polyphenols. Combining the
      coagulation/flocculation pre-treatment with Fenton reagent, it was possible to
      reach 89% of COD removal in 96 h. Moreover, coagulation/flocculation combined
      with solar photo-Fenton revealed higher DOC (75%) reductions than single solar
      photo-Fenton (54%). In the combined treatment (coagulation/flocculation and solar
      photo-Fenton), it was reached a DOC reduction of 50% after the chemical
      oxidation, with 110 kJ L(-1) of accumulated UV energy and a H2O2 consumption of
      116 mM. Toxicity and biodegradability assays were performed to evaluate possible
      variations along the oxidation processes. After the combined treatment, the
      leachate under study presented non-toxicity but biodegradability increased.

PMID- 25590820
TI  - Enhanced tolerance and remediation to mixed contaminates of PCBs and 2,4-DCP by
      transgenic alfalfa plants expressing the 2,3-dihydroxybiphenyl-1,2-dioxygenase.
AB  - Polychlorinated biphenyls (PCBs) and 2,4-dichlorophenol (2,4-DCP) generally led
      to mixed contamination of soils as a result of commercial and agricultural
      activities. Their accumulation in the environment poses great risks to human and
      animal health. Therefore, the effective strategies for disposal of these
      pollutants are urgently needed. In this study, genetic engineering to enhance
      PCBs/2,4-DCP phytoremediation is a focus. We cloned the 2,3-dihydroxybiphenyl-1,2
      dioxygenase (BphC.B) from a soil metagenomic library, which is the key enzyme of
      aerobic catabolism of a variety of aromatic compounds, and then it was expressed
      in alfalfa driven by CaMV 35S promoter using Agrobacterium-mediated
      transformation. Transgenic line BB11 was selected out through PCR, Western blot
      analysis and enzyme activity assays. Its disposal and tolerance to both PCBs and
      2,4-DCP were examined. The tolerance capability of transgenic line BB11 towards
      complex contaminants of PCBs/2,4-DCP significantly increased compared with non
      transgenic plants. Strong dissipation of PCBs and high removal efficiency of 2,4
      DCP were exhibited in a short time. It was confirmed expressing BphC.B would be a
      feasible strategy to help achieving phytoremediation in mixed contaminated soils
      with PCBs and 2,4-DCP. 

PMID- 25590821
TI  - Mechanism for enhanced degradation of clofibric acid in aqueous by catalytic
      ozonation over MnOx/SBA-15.
AB  - Comparative experiments were conducted to investigate the catalytic ability of
      MnO(x)/SBA-15 for the ozonation of clofibric acid (CA) and its reaction
      mechanism. Compared with ozonation alone, the degradation of CA was barely
      enhanced, while the removal of TOC was significantly improved by catalytic
      ozonation (O3/MnO(x)/SBA-15). Adsorption of CA and its intermediates by
      MnO(x)/SBA-15 was proved unimportant in O3/MnO(x)/SBA-15 due to the insignificant
      adsorption of CA and little TOC variation after ceasing ozone in stopped-flow
      experiment. The more remarkably inhibition effect of sodium bisulfite (NaHSO3) on
      the removal of TOC in catalytic ozonation than in ozonation alone elucidated that
      MnO(x)/SBA-15 facilitated the generation of hydroxyl radicals (OH), which was
      further verified by electron spin-resonance spectroscopy (ESR). Highly dispersed
      MnO(x) on SBA-15 were believed to be the main active component in MnO(x)/SBA-15.
      Some intermediates were indentified and different degradation routes of CA were
      proposed in both ozonation alone and catalytic ozonation. The amounts of small
      molecular carboxylic acids (i.e., formic acid (FA), acetic acid (AA) and oxalic
      acid (OA)) generated in catalytic ozonation were lower than in ozonation alone,
      resulting from the generation of more OH.

PMID- 25590822
TI  - Biodegradation of bisphenol A with diverse microorganisms from river sediment.
AB  - The wide distribution of bisphenol A (BPA) in the environment is problematic
      because of its endocrine-disrupting characteristics and toxicity. Developing cost
      effective remediation methods for wide implementation is crucial. Therefore, this
      study investigated the BPA biodegradation ability of various microorganisms from
      river sediment. An acclimated microcosm completely degraded 10 mg L(-1) BPA
      within 28 h and transformed the contaminant into several metabolic intermediates.
      During the degradation process, the microbial compositions fluctuated and the
      final, predominant microorganisms were Pseudomonas knackmussii and Methylomonas
      clara. From the original river sediment, we isolated four distinct strains, which
      deplete the BPA over 7-9 days. They were all genetically similar to P.
      knackmussii. The degradation ability of mixed strains was higher than that of
      single strain but was far less than that of the microbial consortium. The novel
      BPA degradation ability of P. knackmussii and its role in the decomposing
      microcosm were first demonstrated. Our results revealed that microbial diversity
      plays a crucial role in pollutant decomposition.

PMID- 25590823
TI  - Reductive dissolution of ferrihydrite with the release of As(V) in the presence
      of dissolved S(-II).
AB  - In this study, reductive dissolution of As(V)-ferrihydrite and the mobilization
      of As(V) in the presence of S(-II) were investigated under anoxic conditions.
      Mobilization of As(V) strongly depended on the S(-II):Fe ratio and the amount of
      As(V) loading on ferrihydrite. High S(-II):Fe ratio caused a more complete
      dissolution of ferrihydrite and a large fraction of As(V) could be released into
      solution. The percentages of the released As(V) were 2.5% and 7.5% at S(-II):Fe
      ratios of 0.240 and 24.0, respectively, at pH 6.1, while the released As(V) were
      5.5%, 16.3% at pH 8.0 under similar conditions. As(V) loading showed a negative
      effect on the release of arsenate, with smaller fraction of arsenate released
      into solution when more As (V) adsorbed on ferrihydrite. After 43 h, 14.1%, 5.5%,
      1.6% and 0.7% of As(V) were released as for 10, 20, 50 and 100 mg L(-1) of As(V)
      loading, respectively, at pH 8.0. During the dissolution, secondary minerals such
      as goethite, magnetite and FeS were detected and played different roles in the
      mobilization of As(V). The released As(V) was mainly repartitioned on the
      residual ferrihydrite, the newly-formed goethite and magnetite but not FeS.

PMID- 25590824
TI  - Interactions between nano-TiO2 and the oral cavity: impact of nanomaterial
      surface hydrophilicity/hydrophobicity.
AB  - Titanium dioxide (TiO2) nanoparticles are available in a variety of oral
      applications, such as food additives and cosmetic products. Thus, questions about
      their potential impact on the oro-gastrointestinal route rise. The oral cavity
      represents the first portal of entry and is known to rapidly interact with
      nanoparticles. Surface charge and size contribute actively to the particle-cell
      interactions, but the influence of surface hydrophilicity/hydrophobicity has
      never been shown before. This study addresses the biological impact of
      hydrophilic (NM 103, rutile, 20 nm) and hydrophobic (NM 104, rutile, 20 nm) TiO2
      particles within the buccal mucosa. Particle characterization was addressed with
      dynamic light scattering and laser diffraction. Despite a high agglomeration
      tendency, 10% of the particles/agglomerates were present in the nanosized range
      and penetrated into the mucosa, independent of the surface properties. However,
      significant differences were observed in intracellular particle localization. NM
      104 particles were found freely distributed in the cytoplasm, whereas their
      hydrophobic counterparts were engulfed in vesicular structures. Although cell
      viability/membrane integrity was not affected negatively, screening assays
      demonstrated that NM 104 particles showed a higher potential to decrease the
      physiological mitochondrial membrane potential than NM 103, resulting in a
      pronounced generation of reactive oxygen species.

PMID- 25590825
TI  - Anaerobic biodegradation of nonylphenol in river sediment under nitrate- or
      sulfate-reducing conditions and associated bacterial community.
AB  - Nonylphenol (NP) is a commonly detected pollutant in aquatic ecosystem and can be
      harmful to aquatic organisms. Anaerobic degradation is of great importance for
      the clean-up of NP in sediment. However, information on anaerobic NP
      biodegradation in the environment is still very limited. The present study
      investigated the shift in bacterial community structure associated with NP
      degradation in river sediment microcosms under nitrate- or sulfate-reducing
      conditions. Nearly 80% of NP (100 mg kg(-1)) could be removed under these two
      anaerobic conditions after 90 or 110 days' incubation. Illumina MiSeq sequencing
      analysis indicated that Proteobacteria, Firmicutes, Bacteroidetes and Chloroflexi
      became the dominant phylum groups with NP biodegradation. The proportion of
      Gammaproteobacteria, Deltaproteobacteria and Choloroflexi showed a marked
      increase in nitrate-reducing microcosm, while Gammaproteobacteria and Firmicutes
      in sulfate-reducing microcosm. Moreover, sediment bacterial diversity changed
      with NP biodegradation, which was dependent on type of electron acceptor.

PMID- 25590826
TI  - Facile functionalized of SBA-15 via a biomimetic coating and its application in
      efficient removal of uranium ions from aqueous solution.
AB  - A novel dopamine-functionalized mesoporous silica (DMS), synthesized by grafting
      dopamine onto a mesoporous molecular sieve (SBA-15), was developed as a sorbent
      to extract U(VI) from aqueous solution. The method used to modify SBA-15 was
      simple, facile and cost-effective. The DMS was characterized by SEM, TEM, XRD and
      BET, showing that the material had an ordered mesoporous structure and a large
      surface area. The effect of contact time, pH, ionic strength, temperature, and
      solid-liquid ratio on the sorption process was investigated. It was demonstrated
      that the adsorption of U(VI) by DMS was fast and that it can be described by the
      pseudo-second order-equation where the equilibrium time was 20 min. Additionally,
      the adsorption isotherm data were fitted well by the Langmuir model with the
      maximum adsorption capacity of DMS of 196 mg/g at pH 6.0. Furthermore, the
      influence of the K(+) and Na(+) concentrations and solid-to-liquid ratio on the
      sorption was very weak, and the values of the thermodynamic parameters revealed
      that the sorption process was exothermic and spontaneous. All the results
      suggested that the DMS could be used as an excellent adsorbent to remove U(VI)
      from aqueous solution.

PMID- 25590827
TI  - Dispersive liquid-liquid microextraction based on the solidification of floating
      organic drop followed by ICP-MS for the simultaneous determination of heavy
      metals in wastewaters.
AB  - In the present work, a dispersive liquid-liquid microextraction based on the
      solidification of floating organic drop (DLLME-SFO) combined with inductively
      coupled plasma mass spectrometry (ICP-MS) was developed for the determination of
      Pb, Co, Cu, Ni, Zn. The influences of analytical parameters, including pH,
      extraction solvent volume, disperser solvent volume, concentration of chelating
      agent on the quantitative recoveries of Pb, Co, Cu, Ni, Zn were investigated. The
      effect of the interfering ions on the analytes recovery was also investigated.
      Under the optimized conditions, the limits of detection were 0.97-2.18 ng L(-1).
      The relative standard deviations (RSDs) were 2.62-4.51% (n=7, C=20 ng L(-1)). The
      proposed method was successfully applied for the analysis of ultra trace metals
      in wastewater samples.

PMID- 25590828
TI  - 3-Phenylpyridinium hydrogen squarate: experimental and computational study of a
      nonlinear optical material.
AB  - The detailed investigation of an organic nonlinear optical (NLO) squarate salt of
      3-phenylpyridinium hydrogen squarate (1), C11H10N+.C4HO4(-), was reported in this
      study. The XRD data indicates that the crystal structure of the title compound is
      in the triclinic P-1 space group. In the asymmetric unit, the 3-phenylpyridine
      molecule is protonated by one hydrogen atom donation of squaric acid molecule,
      forming the salt (1). The X-ray analysis shows that the crystal packing has
      hydrogen bonding ring pattern of D2(2)(10) (alpha-dimer) through NH...O
      interactions. The structural and vibrational properties of the compound were also
      studied by computational methods of ab initio at DFT/B3LYP/6-31++G(d,p) (2) and
      HF/6-31++G(d,p) (3) levels of theory. The calculation results on the basis of two
      models for both the optimized molecular structure and vibrational properties for
      the 1 are presented and compared with the experimental results. Non-linear
      optical properties (NLO) of the title compound together with the molecular
      electrostatic potential (MEP), electronic absorption spectrum, frontier molecular
      orbitals (FMOs) and conformational flexibility were also studied at the 2 level
      and the results were reported. In order to evaluate the suitability for NLO
      applications thermal analysis (TG, DTA and DTG) data of 1 were also obtained.

PMID- 25590829
TI  - A highly sensitive and selective fluorescent chemosensor for detection of Zn2+
      based on a Schiff base.
AB  - A Schiff-base fluorescent probe - 2-((E)-(quinolin-8-ylimino)methyl)quinolin-8-ol
      (H7L) was synthesized and evaluated as a chemoselective Zn2+ sensor. Upon
      treatment with Zn2+, the complexation of H7L with Zn2+ resulted in a red shift
      with a pronounced enhancement in the fluorescence emission intensity in ethanol
      solution. Moreover, other common alkali, alkaline earth and transition metal ions
      failed to induce response or minimal spectral changes. Notably, this chemosensor
      could distinguish clearly Zn2+ from Cd2+. Fluorescence studies on H7L and H7L
      Zn2+ complex reveal that the quantum yield strongly increases upon coordination.
      The stoichiometric ratio and association constant were evaluated using Benesi
      Hildebrand relation giving 1:1 stoichiometry. This further corroborated 1:1
      complex formation based on Job's plot analyses. This chemosensor exhibits a very
      good fluorescence sensing ability to Zn2+ over a wide range of pH.

PMID- 25590830
TI  - Cytotoxic activity of rearranged drimane meroterpenoids against colon cancer
      cells via down-regulation of beta-catenin expression.
AB  - Colorectal cancer has emerged as a major cause of death in Western countries.
      Down-regulation of beta-catenin expression has been considered a promising
      approach for cytotoxic drug formulation. Eight 4,9-friedodrimane-type
      sesquiterpenoids (1-8) were acquired using the oxidative potential of Verongula
      rigida on bioactive metabolites from two Smenospongia sponges. Compounds 3 and 4
      contain a 2,2-dimethylbenzo[d]oxazol-6(2H)-one moiety as their substituted
      heterocyclic residues, which is unprecedented in such types of meroterpenoids.
      Gauge-invariant atomic orbital NMR chemical shift calculations were employed to
      investigate stereochemical details with support of the application of advanced
      statistics such as CP3 and DP4. Compounds 2 and 8 and the mixture of 3 and 4
      suppressed beta-catenin response transcription (CRT) via degrading beta-catenin
      and exhibited cytotoxic activity on colon cancer cells, implying that their anti
      CRT potential is, at least in part, one of their underlying antineoplastic
      mechanisms. 

PMID- 25590831
TI  - The Effect of the Use of Synthetic Mesh Soaked in Antibiotic Solution on the Rate
      of Graft Infection in Ventral Hernias: A Prospective Randomized Study.
AB  - Wound infections and seroma formations are important problems in ventral hernia
      repair operations using synthetic mesh grafts. The aim of this study was to
      investigate the effect of the use of synthetic mesh soaked in vancomycin solution
      on the rate of graft infection. The total number of subjects was 52. The subjects
      were randomized into 2 groups using a software program. Group 1 (n = 26) was the
      control group. In group 2 (n = 26), synthetic mesh was soaked in a Vancomycin
      solution before it was implanted. The patients were compared with respect to
      demographic characteristics and preoperative, intraoperative, and postoperative
      variables. There were no significant differences between the groups with respect
      to the available variables. Seroma development was significantly more common in
      group 2 (P < 0.041). Three patients (5.7%) developed superficial wound infection,
      and 9 (17%) developed surgical site infection 2-type wound-site infection. No
      significant difference was found between the groups in terms of infection. The
      use of synthetic mesh soaked in vancomycin solution had no beneficial effects on
      the rate of wound-site infection. Future randomized, controlled, large-scale
      studies using the same mesh and suture types, and meshes soaked in larger
      spectrum antibiotics are needed. 

PMID- 25590832
TI  - Onychomycosis in Israel: epidemiological aspects.
AB  - Onychomycosis is a fungal infection treated orally for prolonged periods of
      treatment, caused primarily by Dermatophytes, Candida species and non
      dermatophyte moulds (NDMs). The prevalence of specific aetiology may differ in
      dependence of environmental, geographic and demographic factors, and may affect
      management of the infection. The objective of this survey was to analyse
      epidemiologic parameters of onychomycosis in Israel. Data of a cohort of 27,093
      patients were collected from six centres during a 2- and 10-year period. The
      diagnosis was based on microscopy of KOH/calcofluor mounts of nail scrapings and
      culture isolation. A positive result indicates isolation of a fungus in culture.
      Data were analysed for each centre and expressed as range for the whole cohort,
      using the spss v18 software. Analysis included three epidemiologic parameters:
      fungal aetiology in toe- and fingernails; association with gender; association
      with age group. Dermatophytes were the major causative agents and Trichophyton
      rubrum the most frequent isolate. Candida species were more frequent in women
      fingernails; frequency increased with age and C. parapsilosis the most frequent
      species. NDMs were isolated at low rate and Aspergillus terreus was the most
      frequent isolate. This is a first large cohort of onychomycosis patients from
      Israel analysed by defined epidemiological parameters.

PMID- 25590833
TI  - Associations of blood pressure with common factors among left-behind farmers in
      rural China: a cross-sectional study using quantile regression analysis.
AB  - The whole range of blood pressure (BP) has important implications. Yet, published
      studies focus primarily on hypertension and hypotension, the two extremes of BP
      continuum. This study aims at exploring quantile-specific associations of BP with
      common factors. The study used cross-sectional survey, collected information
      about gender, age, education, body mass index (BMI), alcohol intake, diet risk
      behavior, life event index, physical activity, fasting capillary glucose (FCG),
      and systolic/diastolic blood pressure (SBP/DBP) and pulse pressure (PP) from
      farmers living in 18 villages from rural Anhui, China, and performed descriptive
      and multivariate and quantile regression (QR) analysis of associations of SBP,
      DBP, or PP with the 9 factors surveyed. A total of 4040 (86.3%) eligible farmers
      completed the survey. Average hypertension prevalence rate and SBP, DBP, and PP
      values estimated 43.20 +/- 0.50% and 141.37 +/- 21.98, 87.76 +/- 12.23, and 53.63
      +/- 15.72 mm Hg, respectively. Multivariate regression analysis revealed that all
      the 9 factors were significantly (P < 0.05) associated with one or more of SBP,
      DBP, and PP. QR coefficients of SBP, DBP, or PP with different factors
      demonstrated divergent patterns and age, BMI, FCG, and life event index showed
      substantial trends along the quantile axis. Hypertension prevalence rate was high
      among the farmers. QR modeling provided more detailed view on associations of
      SBP, DBP, or PP with different factors and uncovered apparent quantile-related
      patterns for part of the factors. Both the population group studied and the
      trends in QR coefficients identified merit specific attention.

PMID- 25590834
TI  - Low systolic blood pressure and mortality from all-cause and vascular diseases
      among the rural elderly in Korea; Kangwha cohort study.
AB  - The association between low systolic blood pressure (SBP) and vascular diseases
      is unclear. The aim of this study was to prospectively examine the association
      between SBP, especially low SBP, and mortality from all causes and vascular
      diseases among the elderly in Korea. Six thousand two hundred ninety four
      residents in a rural community were followed-up for deaths from 1985 to 2008. The
      adjusted hazard ratios (aHR) and 95% confidence intervals were calculated by Cox
      proportional hazard model. A stratified analysis was conducted by age at
      enrollment. Among the elderly aged 65 and above, the lowest SBP (<100 mm Hg)
      group had an elevated aHR for mortality from vascular diseases (aHR = 2.1, 95% CI
      = 1.2-3.9) including stroke (aHR = 2.4, 95% CI = 0.9-6.3) and ischemic heart
      diseases (aHR = 5.1, 95% CI = 1.0-26.0) compared to those with SBP of 100-119 mm
      Hg, while higher SBP was associated with higher mortality. This J-curve
      association was generally maintained when analysis was restricted to those with
      fair or good self-rated health, or those with no known vascular diseases. In
      people below 65, increasing SBP nearly monotonically increased the mortality from
      all-cause and vascular diseases. Our results suggest that elderly persons with
      low SBP should be treated with caution, since low SBP may increase vascular
      mortality.

PMID- 25590835
TI  - Erlotinib plus capecitabine as first-line treatment for older Chinese patients
      with advanced adenocarcinoma of the lung (C-TONG0807): an open-label, single arm,
      multicenter phase II study.
AB  - Preclinical studies have shown synergism between epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitors and antifolates in solid tumors. This study is
      to investigate the efficacy and tolerability of erlotinib plus capecitabine as
      first-line treatment in older Chinese patients (>= 65 years) with lung
      adenocarcinoma. This is an open-label, single arm, multicenter phase II clinical
      trial. Sixty- two patients with previously untreated stage IIIB/IV adenocarcinoma
      and age 65 years or above were enrolled at four tertiary teaching hospitals and 2
      provincial hospitals in China; 58 patients fulfilled the study requirements.
      Erlotinib (150 mg/day) and capecitabine (1000 mg/m2 twice daily on days 1-14)
      were administered during every 21-day cycle. The primary endpoint was the non
      progression rate at 12 weeks. EGFR and K-ras mutation rates were determined using
      PCR. Tumor expression of different biomarkers was assessed using
      immunohistochemistry. In a cohort of 58 patients, 34 patients had no disease
      progression at 12 weeks following treatment. The objective response rate was
      29.3%, and the disease control rate was 75.9%. The objective response rate was
      significantly higher in patients with EGFR mutations than in those with wild-type
      EGFR. Patients with thymidine phosphorylase-negative tumors had significantly
      longer overall survival after one year than patients with thymidine phosphorylase
      positive tumors. Forty-four patients had at least one primary adverse events
      (AEs), including skin rash (n = 30), grade 3 AEs (n = 17), and grade 4 AEs (n =
      7). This is the first phase II clinical trial to assess erlotinib plus
      capecitabine combination therapy as first-line treatment in older patients with
      lung adenocarcinoma. Erlotinib/capecitabine chemotherapy was significantly better
      in patients with EGFR mutations and in those with thymidine phosphorylase
      negative tumors. The use of fluorouracil derivatives for the treatment of lung
      adenocarcinoma warrants further study.

PMID- 25590836
TI  - Potentially modifiable risk factors for acute kidney injury after surgery on the
      thoracic aorta: a propensity score matched case-control study.
AB  - Perioperative risk factors were identified for acute kidney injury (AKI) defined
      by the RIFLE criteria (RIFLE = risk, injury, failure, loss, end stage) after
      surgery on the thoracic aorta with cardiopulmonary bypass (CPB) in this case
      control study. A retrospective review was completed for 702 patients who
      underwent surgery on the thoracic aorta with CPB. A total of 183 patients with
      AKI were matched 1:1 with patients without AKI by a propensity score. Matched
      variables included age, gender, body-mass index, preoperative creatinine levels,
      estimated glomerular filtration rate, a history of hypertension, diabetes
      mellitus, cerebrovascular accident, smoking history, or chronic obstructive
      pulmonary disease to exclude the influence of patient demographics, preoperative
      medical status, and baseline renal function. Multivariate logistic regression
      analysis was used to evaluate for independent risk factors in the matched sample
      of 366 patients. The incidence of AKI was 28.6% and 5.9% of patients from the
      entire sample required renal replacement therapy. AKI was associated with a
      prolonged postoperative hospital stay and a higher one-month and one-year
      mortality both in the entire and matched sample set. Independent risk factors for
      AKI were a left ventricular ejection fraction <55%, preoperative hemoglobin level
      <10 g/dL, albumin <4.0 g/dL, diagnosis of dissection, operation time >7 hours,
      deep hypothermic circulatory arrest (DHCA) time >30 min, pRBC transfusion >1000
      mL, and FFP transfusion >500 mL. Although the incidence of poor glucose control
      (blood glucose >180 mg/dL) was higher in patients with AKI in matched sample, it
      was not an independent risk factor.AKI was still associated with a poor clinical
      outcome in the matched sample. Potentially modifiable risk factors included
      preoperative anemia and hypoalbuminemia. Efforts to minimize operation time and
      DHCA time along with transfusion amount may protect patients undergoing aortic
      surgery against AKI.

PMID- 25590838
TI  - A metabolic phenotype based on mitochondrial ribosomal protein expression as a
      predictor of lymph node metastasis in papillary thyroid carcinoma.
AB  - Metabolic reprogramming has been regarded as an essential component of malignant
      transformation. However, the clinical significance of metabolic heterogeneity
      remains poorly characterized. The aim of this study was to characterize metabolic
      heterogeneity in thyroid cancers via the analysis of the expression of
      mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative
      phosphorylation (OxPhos), and investigate potential prognostic correlations. Gene
      set enrichment analysis (GSEA) verified by reverse transcription polymerase chain
      reaction and gene network analysis was performed using public repository data.
      Cross-sectional observational study was conducted to classify papillary thyroid
      cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to
      investigate the clinicopathological features. GSEA clearly showed that the
      expression of OxPhos and MRP gene sets was significantly lower in primary thyroid
      cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid
      tumors (16.3%) in the public repository did not show a reduction in OxPhos mRNA
      expression. Remarkably, strong positive correlations between MRPL44 expression
      and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide
      dehydrogenase (ubiquinone) 1 alpha subcomplex, 5; succinate dehydrogenase
      complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+
      transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5
      (MRPS5) (P < 0.0001) were clearly denoted, suggesting that MRPL44 is a
      representative marker of OxPhos and MRP expressions. In laboratory experiments,
      metabolic heterogeneity in oxygen consumption, extracellular acidification rates
      (ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP,
      TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to
      OxPhos amount defined by expression of MRPL44 mRNA was significantly related to
      lymph node metastasis (LNM) (P < 0.001). Furthermore, multivariate analysis
      clearly indicated that expression of MRPL44 is associated with an increased risk
      of lateral neck LNM (odds ratio 9.267, 95% confidence interval 1.852-46.371, P =
      0.007). MRPL44 expression may be a representative marker of metabolic phenotype
      according to OxPhos amount and a useful predictor of LNM.

PMID- 25590837
TI  - Etiology and antimicrobial susceptibility of middle ear fluid pathogens in Costa
      Rican children with otitis media before and after the introduction of the 7
      valent pneumococcal conjugate vaccine in the National Immunization Program: acute
      otitis media microbiology in Costa Rican children.
AB  - Acute otitis media (AOM) microbiology was evaluated in children after 7-valent
      pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector,
      2004; National Immunization Program, 2009). This was a combined prospective and
      retrospective study conducted in a routine clinical setting in San Jose, Costa
      Rica. In the prospective part of the study, which was conducted post-PCV7
      introduction (2010-2012), standard bacteriological procedures were used to
      evaluate the etiology and serotype distribution of middle ear fluid samples
      collected by tympanocentesis or otorrhea from children aged 3-59 months diagnosed
      with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture
      positive samples. Retrospective data recorded between 1999 and 2004 were used for
      comparison of bacterial etiology and serotype distribution before and after PCV7
      introduction. Statistical significance was evaluated in bivariate analyses at the
      P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction,
      Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in
      87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H.
      influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%)
      frequently observed in vaccinated (>= 2 PCV7 doses or >= 1 PCV7 dose at >1 year
      of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were
      1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and
      trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non
      susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7
      introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S.
      pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype
      proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value =
      0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%),
      6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and
      35B (8.0%) post-PCV7 introduction. Following PCV7 introduction, a change in the
      distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes
      included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines
      impact should be further evaluated following broader vaccination coverage.

PMID- 25590839
TI  - TLR4 rs1927911, but not TLR2 rs5743708, is associated with atherosclerotic
      cerebral infarction in the Southern Han population: a case-control study.
AB  - The objective of this study was to explore the association of toll-like receptor
      (TLR) 4 rs1927911 and TLR2 rs5743708 with atherosclerotic cerebral infarction
      (ACI) and their effects on blood pressure, fasting blood glucose, and blood
      lipids in the Han population of Hunan Province. TLR4 rs1927911 and TLR2 rs5743708
      were detected by polymerase chain reaction and restriction fragment length
      polymorphism in 170 patients with ACI and 149 healthy controls. Our results
      indicated that the genotype and allele frequencies of TLR4 rs1927911 were
      significantly different between ACI patients and controls, whereas those of TLR2
      rs5743708 were not significantly different between the 2 groups. For TLR4
      rs1927911, blood pressure, fasting blood sugar, and serum lipid levels were not
      significantly different among different genotypes in the ACI and control groups.
      The rs1927911 polymorphism of the TLR4 gene may be a risk factor for ACI in the
      Southern Han population of Hunan Province; however, it may not be associated with
      blood pressure, fasting blood sugar, or blood lipids.

PMID- 25590840
TI  - Training in early gastric cancer diagnosis improves the detection rate of early
      gastric cancer: an observational study in China.
AB  - Few studies have analyzed the training of endoscopists in the diagnosis of early
      gastric cancer (EGC). This study assessed whether specific training of
      endoscopists improves the detection rate of EGC. The rates of detection of EGC by
      endoscopists at the Digestive Endoscopy Center of the Affiliated Nanfang Hospital
      of China Southern Medical University between January 2013 and May 2014 were
      retrospectively analyzed. Because some endoscopists received training in the
      diagnosis of EGC, beginning in September 2013, the study was divided into 3 time
      periods: January to September 2013 (period 1), September 2013 to January 2014
      (period 2), and January to May 2014 (period 3). The rates of EGC detection during
      these 3 periods were analyzed. From January 2013 to May 2014, a total of 25,314
      gastroscopy examinations were performed at our center, with 48 of these
      examinations (0.2%) detecting EGCs, accounting for 12.1% (48/396) of the total
      number of gastric cancers detected. The EGC detection rates by trained
      endoscopists during periods 1, 2, and 3 were 0.3%, 0.6%, and 1.5%, respectively,
      accounting for 22.0%, 39.0%, and 60.0%, respectively, of the gastric cancers
      detected during these time periods. In comparison, the EGC detection rates by
      untrained endoscopists during periods 1, 2, and 3 were 0.05%, 0.08%, and 0.10%,
      respectively, accounting for 3.1%, 6.0%, and 5.7%, respectively, of the gastric
      cancers detected during these times. After training, the detection rate by some
      trained endoscopists markedly increased from 0.2% during period 1 to 2.3% during
      period 3. Further, the use of magnifying endoscopy with narrow-band imaging (M
      NBI) (odds ratio = 3.1, 95% confidence interval 2.4-4.1, P < 0.001) contributed
      to the diagnosis of EGC. In conclusion, specific training could improve the
      endoscopic detection rate of EGC. M-NBI contributed to the diagnosis of EGC.

PMID- 25590841
TI  - Serum IgG subclasses in autoimmune diseases.
AB  - To characterize serum IgG subclass levels in several autoimmune diseases,
      including primary Sjogren syndrome (pSS), systemic sclerosis (SSc), systemic
      lupus erythematosus (SLE), and primary biliary cirrhosis (PBC). We aimed to
      analyze serum IgG subclass distribution and to test whether serum IgG4 levels are
      elevated in these diseases. Serum IgG subclass levels from 102 pSS, 102 SSc, 100
      SLE, and 59 PBC patients, as well as 40 healthy controls (HCs), were measured
      using the immunonephelometric assay. The distribution of IgG subclasses among
      these autoimmune diseases was analyzed. In this cross-sectional study, serum IgG1
      (IgG1/IgG) and/or IgG3 (IgG3/IgG) were significantly increased, compared with
      those in HCs. Only 6.34% of patients had levels of serum IgG4 >135 mg/dL. There
      were no significant differences in the frequency of elevated serum IgG4 levels
      between patients and HC. In pSS, serum IgG1 levels were much higher than those in
      other disease groups, whereas serum IgG2 and IgG3 levels were most prominently
      increased in PBC. A strikingly different serum IgG subclass distribution was
      detected in patients with autoimmune diseases compared with HCs. Serum IgG
      subclass levels also showed distinct characteristics among different autoimmune
      diseases. Serum IgG4 levels in these patients were lower or not much higher than
      those in HCs, which differed from IgG4-related diseases.

PMID- 25590842
TI  - Surgical resection improves the outcome of the patients with neuroendocrine tumor
      liver metastases: large data from Asia.
AB  - How to properly manage neuroendocrine liver metastasis (NELM) remains debatable,
      and only limited clinical data have been published from Asian population. The
      objective of this study is to identify possible prognostic factors affecting
      overall survival time and to provide a guideline for future clinical practice. A
      retrospective study was performed on 1286 patients who had neuroendocrine tumors
      in our specialized center, and data from 130 patients who had NELM were
      summarized. Demographic and clinicopathologic data, tumor grade, treatment
      method, and prognosis were statistically analyzed. Most of the NELMs originated
      from pancreas (65.4%). Important prognostic factors that included tumor location
      and size were identified with multivariate analysis. Patients with either primary
      tumor resection or liver metastasis resection showed a 5-year survival of 35.7%
      or 33.3%, respectively, whereas resection of both resulted in a 50% 5-year
      survival. More importantly, resection was performed on 7 patients with grade 3
      (G3) tumors, and resulted in 1-year, 3-year, and 5-year survival of 100%, 42.8%,
      and 28.6%, respectively, whereas the other 9 G3 patients without resection died
      within 3 years. P = 0.49 comparing the resected group with nonresected group in
      G3 patients. Besides, the overall 5-year survival rates for resected and
      nonresected patients were 40.5% and 5.4%, respectively. Multiple prognostic
      factors influenced the overall outcome of NELM including patient age, tumor
      location, and size, etc. Aggressive surgical approaches could be considered for
      maximum survival time disregarding the pathological grade of the tumor. Study
      with larger sample size should be considered to reevaluate the recommendation of
      the WHO guidelines for G3 neuroendocrine tumors.

PMID- 25590843
TI  - The role of the harm avoidance personality in depression and anxiety during the
      medical internship.
AB  - To determine whether physicians with harm avoidance (HA) personality traits were
      more prone to developing increased anxiety and depression during the medical
      internship. A prospective longitudinal study of 74 medical interns was carried
      out using repeated measures of symptoms of anxiety and depression with the Beck
      Anxiety and Depression Inventories (BAI and BDI) before, at the 3rd, 6th, and
      12th months during the internship, and 2 weeks after the internship was
      completed. Baseline personality was assessed by the Tridimensional Personality
      Questionnaire with 3 dimensions: novelty-seeking, HA, and reward dependence (RD).
      Levels of both depression and anxiety increased (6.4 and 3.4 on scores for BDI
      and BAI, respectively) during the internship and returned to baseline 2 weeks
      after it ended. HA scores were significantly correlated with depression and
      anxiety (0.3 scores on both the BDI and the BAI) and the scores for RD were
      significantly correlated with anxiety but not with depression. The interaction of
      HA and point in internship showed no significant differences. Internship plays a
      major role in the increase in depression and anxiety. A HA personality was also
      associated with the development of both depression and anxiety.

PMID- 25590844
TI  - Cross-sectional study of the retinal nerve fiber layer thickness at 7 years after
      an acute episode of unilateral primary acute angle closure.
AB  - The purpose of this article is to investigate the long-term retinal nerve fiber
      layer (RNFL) status and determinants of RNFL thinning after an episode of
      unilateral primary acute angle closure (AAC). This cross-sectional study analyzed
      the medical records of consecutive patients with a single episode of unilateral
      AAC from 1999 to 2009 in Hong Kong. The peripapillary RNFL thickness was
      correlated with age, gender, presenting intraocular pressure (IOP), time to laser
      iridotomy, time to cataract extraction, follow-up duration, as well as the last
      IOP, vertical cup-to-disc ratio (CDR), and vision. The fellow uninvolved eye was
      used as a proxy comparison of RNFL loss in the attack eye. In 40 eligible
      patients, the mean age was 68.3 +/- 8.7 years with a male-to-female ratio of 1:7.
      The mean presenting IOP was 49.2 +/- 14.0 mm Hg and the time from presentation to
      laser iridotomy was 6.7 +/- 6.9 days. Forty percent of subjects received a
      cataract extraction at 3.2 +/- 2.9 years after the attack. The last IOP, CDR, and
      LogMAR vision were 16.0 +/- 3.8 mm Hg, 0.6 +/- 0.2, and 0.6 +/- 0.6 LogMAR units,
      respectively, at 7.9 +/- 2.4 years. The RNFL thickness in the attack eye (69.2 +/
      19.1 MUm) was 25.2 +/- 17.9% thinner than the fellow eye (93.0 +/- 17.8 MUm) at
      7.5 +/- 2.9 years post-AAC. Using univariate analysis, the last vertical CDR
      (odds ratio [OR] = 17.2, P = 0.049) and LogMAR visual acuity (VA) (OR = 6.6, P =
      0.03) were the only significant predictors for RNFL thinning whereas none of the
      other covariates showed significant associations (P > 0.1). At 7.5 years
      following unilateral AAC, the RNFL thickness was 25% thinner than the fellow eye.
      CDR enlargement and poor VA were the only significant predictors for RNFL loss.

PMID- 25590845
TI  - Cinacalcet in pediatric and adolescent chronic kidney disease: a single-center
      experience.
AB  - Cinacalcet, a calcimimetic drug, has been shown to be efficacious in adult
      chronic kidney disease (CKD) patients; however, it was not fully studied in
      pediatric CKD patients. We aimed at assessing the effect of cinacalcet on intact
      parathyroid hormone (iPTH) secretion in children with CKD-4/5 with iPTH
      consistently >= 300 pg/mL refractory to conventional treatment. This is a
      prospective cohort analysis of 28 children with uncontrolled hyper-parathyroidism
      secondary to stage 4 and 5 CKD admitted to a tertiary center during the period
      from April 2012 to April 2014. Twenty-eight patients with CKD-4/5 were assessed
      prospectively regarding bone biochemistry, renal ultrasonography, serum iPTH
      level, and medications. Patients were classified into 3 groups: group 1, 6
      patients with CKD-4 on supplemental and supportive therapy; group 2, 6 patients
      with CKD-5 on hemodialysis and; group 3, 16 patients with CKD-5 on automated
      peritoneal dialysis. Patients were between the ages of 9 months and 18 years on
      commencing cinacalcet at doses of 0.5 to 1.5 mg/kg. All patients showed at least
      a 60% reduction in iPTH (60%-97%). Highly significant reduction in iPTH and serum
      alkaline phosphatase levels was detected post-cinacalcet. The serum calcium (Ca),
      phosphate (P), and Ca * P product were unaffected. Treatment was well tolerated
      with no hypophosphatemia, hypocalcemia, or other adverse effects almost in all
      patients. Cinacalcet use was proven safe for all pediatric and adolescent
      patients with CKD-4/5 during the study period, and at the same time most of the
      patients reached the suggested iPTH target values.

PMID- 25590846
TI  - Establishment and validation of ALPH-Q score to predict mortality risk in
      patients with acute-on-chronic hepatitis B liver failure: a prospective cohort
      study.
AB  - Currently, there are no robust models for predicting the outcome of acute-on
      chronic hepatitis B liver failure (ACHBLF). We aimed to establish and validate a
      new prognostic scoring system, named ALPH-Q, that integrates electrocardiography
      parameters that may be used to predict short-term mortality of patients with
      ACHBLF. Two hundred fourteen patients were included in this study. The APLH-Q
      score was constructed by Cox proportional hazard regression analysis and was
      validated in an independent patient cohort. The area under the receiver-operating
      characteristic curve was used to compare the performance of different models,
      including APLH-Q, Child-Pugh score (CPS), model of end-stage liver disease
      (MELD), and a previously reported logistic regression model (LRM). The APLH-Q
      score was constructed with 5 independent risk factors, including age (HR = 1.034,
      95% CI: 1.007-1.061), liver cirrhosis (HR = 2.753, 95% CI: 1.366-5.548),
      prothrombin time (HR = 1.031, 95% CI: 1.002-1.062), hepatic encephalopathy (HR =
      2.703, 95% CI: 1.630-4.480), and QTc (HR = 1.008, 95% CI: 1.001-1.016). The
      performance of the ALPH-Q score was significantly better than that of MELD and
      CPS in both the training (0.896 vs 0.712, 0.896 vs 0.738, respectively, both P <
      0.05) and validation cohorts (0.837 vs 0.689, 0.837 vs 0.585, respectively, both
      P < 0.05). Compared with LRM, APLH-Q also showed a better performance (0.896 vs
      0.825, 0.837 vs 0.818, respectively).We have developed a novel APLH-Q score with
      greater performance than CPS, MELD, and LRM for predicting short-term mortality
      of patients with ACHBLF.

PMID- 25590847
TI  - Ectopic variceal bleeding from colonic stoma: two case reports.
AB  - Parastomal variceal bleeding is a rare complication of portal hypertension, which
      often occurs in a recurrent manner and might be life-threatening in extreme
      situations. Treatment options vary, and no standard therapy has been established.
      Herein, we report 2 such cases. The first patient suffered from parastomal
      variceal bleeding after Hartmann procedure for rectal cancer. Stomal revision was
      performed, but bleeding recurred 1 month later. The second patient developed the
      disease after Miles procedure for rectal cancer. Embolization via the
      percutaneous transhepatic approach was performed using the Onyx liquid embolic
      system (LES) (Micro Therapeutics Inc, dba ev3 Neurovascular) in combination with
      coils, and satisfactory results were obtained after a 4-month follow-up. Our
      cases illustrate that surgical revision should be used with caution as a
      temporary solution due to the high risk of rebleeding, whereas transhepatic
      embolization via the Onyx LES and coils could be considered a safe and effective
      choice for skillful managers.

PMID- 25590848
TI  - Pediatric fractures through the eyes of parents: an observational study.
AB  - The present study is an observational cross-sectional study. The main purpose of
      this research was to analyze the perception and behaviors of parents in a series
      of pediatric upper extremity fracture cases. Hundred and seventeen patients
      younger than 12 years who were conservatively treated for the upper extremity
      fracture were included in our study. Parents of the patients were requested to
      answer a family-centered questionnaire related to their child's fracture and its
      treatment. When the parents were asked whether they believe casting would be
      sufficient or not as the treatment of their child's fracture, 84.6% answered
      'yes', 13.7% answered 'I am not sure,' and 1.7% answered 'no.' Sixty-four of the
      parents were not worried about any residual defect in joint or extremity
      functions related to fracture, whereas 21 were worried and 32 were not sure on
      this. The rate of searching further information about the child's fracture was
      34.2% and the mostly used source was the Internet. Twenty-eight of the 117
      respondents (23.9%) emphasized that they would reduce the time their child spend
      outside the home at least for a while after the removal of cast. When
      conservatively treating a child's fracture, physicians dealing with traumatology
      should always consider the parents' perception and behaviors as critically
      important.

PMID- 25590849
TI  - Dissociative symptoms and mother's marital status in young adult population.
AB  - Current findings suggest that mother's marital status indicating father's absence
      or conflicting relationship to father may be specifically related to dissociation
      and other stress-related symptoms. We have assessed relationships of mother's
      marital status, dissociative symptoms, and other psychopathological
      manifestations in a sample of 19 years' old young adults (N = 364) participating
      in European longitudinal study (European Longitudinal Study of Parenthood and
      Childhood). The results show clinically significant manifestations of
      dissociative symptoms in young adult men whose mothers were fatherless and in
      women whose mothers were re-married. Other psychopathological symptoms did not
      reach clinically significant manifestations. The results suggest that significant
      factor related to high level of dissociative symptoms in men growing in
      fatherless families might be linked with disturbed and conflicting attachment to
      a father's figure and pathological dependent attachment to mother. In women
      dissociative symptoms likely are linked to conflicting relationship between
      mother and daughter associated with stepfather' presence in the family.

PMID- 25590850
TI  - Vascular dysregulation in normal-tension glaucoma is not affected by structure
      and function of the microcirculation or macrocirculation at rest: a case-control
      study.
AB  - In normal-tension glaucoma (NTG), optic nerve damage occurs despite a normal
      intraocular pressure. Studies implicating systemic blood pressure or, more
      recently, arterial stiffness in the pathophysiology of NTG have produced
      conflicting results. Our aim was to investigate whether NTG is associated with
      alterations in the macrocirculation or microcirculation, cardiac function, and
      peripheral and central hemodynamics. Thirty patients with NTG (mean age 65 years,
      range 46-79) and 33 healthy subjects (mean age 67 years, range 42-79) matched for
      age and sex were included in the study. Exclusion criteria (for both cases and
      controls) were history of cardiovascular disease, diabetes mellitus, severe
      hypertension, and hypercholesterolemia. Aortic stiffness was measured using
      carotid-femoral pulse wave velocity (PWV), central hemodynamics using carotid
      artery applanation tonometry, and diameter, stiffness, and intima-media thickness
      (IMT) of the carotid and femoral artery using echo-tracking. Total peripheral
      resistance index (TPRI) was derived from mean arterial pressure and cardiac
      index, measured using ultrasound. There were no statistically significant
      differences in arterial structure nor function between NTG patients and age and
      sex-matched controls. NTG versus controls, respectively: brachial blood pressure
      126 +/- 15/77 +/- 8 versus 127 +/- 16/76 +/- 7 mm Hg, P = 0.81; carotid-femoral
      PWV 9.8 +/- 2.1 versus 10.1 +/- 1.9 m/s, P = 0.60; TPRI 1833 +/- 609 versus 1779
      +/- 602 dyne.s/cm5/m2, P = 0.79; and carotid IMT 0.65 +/- 0.14 versus 0.68 +/-
      0.13 mm, P = 0.39. This study could not show an association of NTG with altered
      IMT, arterial stiffness, total peripheral resistance, cardiac output, and
      peripheral or central hemodynamics at rest. Although the majority of these NTG
      patients do exhibit symptoms of vascular dysregulation, in the present study this
      was not translated into alterations in the microcirculation or macrocirculation
      at rest.

PMID- 25590851
TI  - Impaired systolic blood pressure recovery and heart rate recovery after graded
      exercise in patients with metabolic syndrome.
AB  - The aim of this study was to evaluate and compare systolic blood pressure
      recovery and heart rate recovery (HRR) values obtained at various time intervals
      after maximal graded exercise treadmill testing between patients with metabolic
      syndrome (MS) and the controls without MS. To our knowledge, this is the first
      study indicating systolic blood pressure recovery (SBPR) impairment and its
      relations to HRR and other variables in this group of patients. The study
      population included 110 patients with MS (67 men, 43 women; mean age: 46 +/- 9
      years) and 110 control subjects who did not meet the criteria for MS (58 men, 52
      women; mean age: 44 +/- 10 years). All patients were selected from nonobese,
      apparently healthy sedentary individuals who had the ability to perform maximum
      exercise testing. SBPR was assessed by calculating the ratio of systolic blood
      pressure (SBP) obtained in the third minute of the recovery period to either the
      peak-exercise SBP or the SBP in the first minute of the recovery period after
      graded exercise testing. HRR values were calculated by subtracting the HR at the
      first, second, third, fourth, and fifth minutes of the recovery period from the
      HR reached at peak exercise. There was no significant difference found between
      the 2 groups with respect to age and sex distribution. As expected, patients with
      MS had higher waist circumference, fasting plasma glucose and serum triglyceride,
      and lower high-density lipoprotein cholesterol compared with control subjects.
      All HRR values calculated in the first, second, third, fourth, and fifth minutes
      were significantly detected lower in the MS group compared with the control group
      (HRR 1st: 32 +/- 10 vs 36 +/- 11; P = 0.009; HRR 2nd: 47 +/- 10 vs 51 +/- 11; P =
      0.02; HRR 3rd: 53 +/- 11 vs 58 +/- 12; P = 0.001; HRR 4th: 57 +/- 11 vs 64 +/-
      12; P < 0.001; HRR 5th: 60 +/- 16 vs 69 +/- 15; P < 0.001). In addition,
      calculated mean values for SBPR1 and SBPR2 were >1 in patients with MS (1.01 +/-
      0.2 vs 0.91 +/- 0.1 and 1.01 +/- 0.1 vs 0.94 +/- 0.1) and these were
      statistically significant compared with the control group (P < 0.001 and P =
      0.002, respectively). The existence of MS was found to be the only parameter that
      was independently and positively related to SBPR values in the study population.
      Our findings suggest that only the existence of MS itself, not the presence of
      any MS components, is independently associated with SBPRs. We are of the opinion
      that significantly impaired SBPR values, in addition to the decreased HRR values
      observed in this group of patients, such as those with MS, may especially help
      identify patients with potentially increased cardiovascular risk despite normal
      exercise stress testing findings.

PMID- 25590852
TI  - Age-adjusted Charlson comorbidity index scores as predictor of survival in
      colorectal cancer patients who underwent surgical resection and chemoradiation.
AB  - We studied the effect of Age-Adjusted Comorbidity Index Score in colorectal
      cancer patients who underwent similarly aggressive treatment. Using the National
      Health Insurance Research Database of Taiwan, we identified 5643 patients with
      colorectal cancer who underwent surgical resection and chemoradiation from 2007
      through 2011. We estimated survival according to Age-Adjusted Comorbidity Index
      Scores and 5-year survival using Cox proportional hazard regression analysis,
      adjusting for sex, oxaliplatin-based chemotherapy, socioeconomic status,
      geographic region, and hospital characteristics. In the cohort were 3230 patients
      with colonic cancer and 2413 patients with rectal cancer, who had undergone
      combined surgical resection and either neoadjuvant or adjuvant chemoradiation.
      After adjusting for patient characteristics (sex, oxaliplatin-based chemotherapy,
      socioeconomic status, geographic region, and hospital-characteristics), colonic
      cancer patients with age-adjusted Charlson (AAC) >= 6 had a 106% greater risk of
      death within 5 years (adjusted HR = 2.06; 95% CI, 1.66-2.56). In rectal cancer
      patients, patients with an AAC score of 4-5 had a 28% greater risk of death
      within 5 years (adjusted HR = 1.28; 95% CI, 1.02-1.61), and those with AAC >= 6
      had a 47% greater risk (adjusted HR = 1.47; 95% CI, 1.15-1.90). Age and burden of
      comorbidities influence survival of patients with colonic or rectal cancer. Age
      Adjusted Comorbidity Score remains an independent prognostic factor even after
      adjusting for the aggressiveness of treatment.

PMID- 25590854
TI  - Use of MALDI-TOF mass spectrometry and a custom database to characterize bacteria
      indigenous to a unique cave environment (Kartchner Caverns, AZ, USA).
AB  - MALDI-TOF mass spectrometry has been shown to be a rapid and reliable tool for
      identification of bacteria at the genus and species, and in some cases, strain
      levels. Commercially available and open source software tools have been developed
      to facilitate identification; however, no universal/standardized data analysis
      pipeline has been described in the literature. Here, we provide a comprehensive
      and detailed demonstration of bacterial identification procedures using a MALDI
      TOF mass spectrometer. Mass spectra were collected from 15 diverse bacteria
      isolated from Kartchner Caverns, AZ, USA, and identified by 16S rDNA sequencing.
      Databases were constructed in BioNumerics 7.1. Follow-up analyses of mass spectra
      were performed, including cluster analyses, peak matching, and statistical
      analyses. Identification was performed using blind-coded samples randomly
      selected from these 15 bacteria. Two identification methods are presented:
      similarity coefficient-based and biomarker-based methods. Results show that both
      identification methods can identify the bacteria to the species level. 

PMID- 25590855
TI  - Evaluation of 28 cases of mucormycosis.
AB  - Mucormycosis is a rare but invasive fungal disease with high mortality. The
      present study aimed to retrospectively investigate the demographic
      characteristics, as well as the clinical, radiological and laboratory features
      and the results of treatment, in the patients followed in our hospital because of
      mucormycosis. The present study retrospectively evaluated 28 cases, which were
      followed in our hospital because of mucormycosis between January 2002 and July
      2013. The clinical form was rhinocerebral in 27 cases (rhinoorbital in 12, nasal
      in 8 and rhinoorbitocerebral in 7) and disseminated in one case. With regard to
      predisposing factors, diabetes mellitus (n = 20), haematological malignancy (n =
      6) and chronic renal insufficiency (n = 5) were the leading concomitant diseases.
      Seventeen (61%) of 28 cases showed atypical clinical picture. With regard to the
      therapeutic outcomes; it was found that 14 (50%) cases died and six cases
      recovered with sequel. Today, when particularly the prevalence of
      immunosuppressive diseases and conditions are gradually increasing, the incidence
      of mucormycosis is also increased. Considering that the majority of our cases had
      atypical clinical involvement and complications, being familiar with the
      characteristics of this disease could be life-saving together with early
      diagnosis and treatment. 

PMID- 25590856
TI  - EVOLUTION OF CONTROLLING DIABETIC RETINOPATHY: Changing Trends in the Management
      of Diabetic Macular Edema at a Single Institution Over the Past Decade.
AB  - PURPOSE: To report the evolution of treatment in managing diabetic macular edema
      (DME) in a "real world" clinical setting. METHODS: Retrospective observational
      case series of 1,862 patients treated for DME over the last decade. Change in
      selection of treatment modalities used for controlling DME, visual acuity, and
      degree of DME on optical coherence tomography were recorded. RESULTS: Over the
      past decade, there was a linear decrease in laser use, with exponential growth in
      the utilization of intravitreal injections. An increase in the frequency of
      clinic visits from 3 +/- 2 visits per year to 9 +/- 2 visits per year with
      significant visual and anatomical improvements was noted: mean improvement in
      visual acuity increased from 0.01 +/- 0.1 logMAR units (which is equivalent to
      less than 1 Snellen line) to 0.3 +/- 0.2 logMAR units (which is equivalent to 2
      Snellen lines) (P < 0.05), mean decrease in retinal thickness changed from 58 +/-
      59 MUm to 162 +/- 91 MUm (P < 0.05). CONCLUSION: An evolution in treatment
      strategy for controlling DME over the last decade was reflected by the
      replacement of focal laser therapy with intravitreal injections. This has
      produced significant improvements in visual and anatomical outcomes but has
      increased the frequency of office visits.

PMID- 25590857
TI  - Changes of choroidal neovascularization in indocyanine green angiography after
      intravitreal ranibizumab injection.
AB  - PURPOSE: To investigate vascular structural changes of choroidal
      neovascularization (CNV) followed by intravitreal ranibizumab injections using
      indocyanine green angiography. METHODS: A total of 31 patients with exudative age
      related macular degeneration and CNV whose structures were identifiable in
      indocyanine green angiography were included. Ranibizumab was injected into the
      vitreous cavity once a month for 3 months and then as needed for the next 3
      months prospectively. Indocyanine green angiography was performed at baseline, 3,
      and 6 months. Early to midphase images of the indocyanine green angiography in
      the details of vascular structure of the CNV were discerned the best were used in
      the image analysis. Vascular structures of CNV were described as arteriovenular
      and capillary components, and structural changes were assessed. RESULTS:
      Arteriovenular components were observed in 29 eyes (94%). Regression of the
      capillary components was observed in most cases. Although regression of
      arteriovenular component was noted in 14 eyes (48%), complete resolution was not
      observed. The eyes were categorized into 3 groups according to CNV structural
      changes: the regressed (Group R, 10 eyes, 31%), the matured (Group M, 7 eyes,
      23%), and the growing (Group G, 14 eyes, 45%). In Group R, there was no regrowth
      of CNV found at 6 months. In Group M, distinct vascular structures were observed
      at 3 months and persisted without apparent changes at 6 months. In Group G,
      growth or reperfusion of capillary components from the persisting arteriovenular
      components was noted at 6 months. CONCLUSION: Both capillary and arteriovenular
      components were regressed during monthly ranibizumab injections. However, CNV
      regrowth was observed in a group of patients during the as-needed treatment
      phase.

PMID- 25590858
TI  - Asymmetric alpha-benzoyloxylation of beta-ketocarbonyls by a chiral primary amine
      catalyst.
AB  - The direct asymmetric alpha-benzoyloxylation of beta-ketocarbonyls catalyzed by a
      chiral primary amine is described herein. This protocol demonstrates excellent
      enantioselectivity for a broad range of substrates, which allows convenient
      access to highly enantioenriched alpha-hydroxy-beta-ketocarbonyls. 

PMID- 25590859
TI  - High throughput characterization of adult stem cells engineered for delivery of
      therapeutic factors for neuroprotective strategies.
AB  - Mesenchymal stem cells (MSCs) derived from bone marrow are a powerful cellular
      resource and have been used in numerous studies as potential candidates to
      develop strategies for treating a variety of diseases. The purpose of this study
      was to develop and characterize MSCs as cellular vehicles engineered for delivery
      of therapeutic factors as part of a neuroprotective strategy for rescuing the
      damaged or diseased nervous system. In this study we used mouse MSCs that were
      genetically modified using lentiviral vectors, which encoded brain-derived
      neurotrophic factor (BDNF) or glial cell-derived neurotrophic factor (GDNF),
      together with green fluorescent protein (GFP). Before proceeding with in vivo
      transplant studies it was important to characterize the engineered cells to
      determine whether or not the genetic modification altered aspects of normal cell
      behavior. Different culture substrates were examined for their ability to support
      cell adhesion, proliferation, survival, and cell migration of the four
      subpopulations of engineered MSCs. High content screening (HCS) was conducted and
      image analysis performed. Substrates examined included: poly-L-lysine,
      fibronectin, collagen type I, laminin, entactin-collagen IV-laminin (ECL). Ki67
      immunolabeling was used to investigate cell proliferation and Propidium Iodide
      staining was used to investigate cell viability. Time-lapse imaging was conducted
      using a transmitted light/environmental chamber system on the high content
      screening system. Our results demonstrated that the different subpopulations of
      the genetically modified MSCs displayed similar behaviors that were in general
      comparable to that of the original, non-modified MSCs. The influence of different
      culture substrates on cell growth and cell migration was not dramatically
      different between groups comparing the different MSC subtypes, as well as culture
      substrates. This study provides an experimental strategy to rapidly characterize
      engineered stem cells and their behaviors before their application in long-term
      in vivo transplant studies for nervous system rescue and repair. 

PMID- 25590860
TI  - Molecular details of INH-C10 binding to wt KatG and Its S315T mutant.
AB  - Isoniazid (INH) is still one of the two most effective antitubercular drugs and
      is included in all recommended multitherapeutic regimens. Because of the
      increasing resistance of Mycobacterium tuberculosis to INH, mainly associated
      with mutations in the katG gene, new INH-based compounds have been proposed to
      circumvent this problem. In this work, we present a detailed comparative study of
      the molecular determinants of the interactions between wt KatG or its S315T
      mutant form and either INH or INH-C10, a new acylated INH derivative. MD
      simulations were used to explore the conformational space of both proteins, and
      results indicate that the S315T mutation did not have a significant impact on the
      average size of the access tunnel in the vicinity of these residues. Our
      simulations also indicate that the steric hindrance role assigned to Asp137 is
      transient and that electrostatic changes can be important in understanding the
      enzyme activity data of mutations in KatG. Additionally, molecular docking
      studies were used to determine the preferred modes of binding of the two
      substrates. Upon mutation, the apparently less favored docking solution for
      reaction became the most abundant, suggesting that S315T mutation favors less
      optimal binding modes. Moreover, the aliphatic tail in INH-C10 seems to bring the
      hydrazine group closer to the heme, thus favoring the apparent most reactive
      binding mode, regardless of the enzyme form. The ITC data is in agreement with
      our interpretation of the C10 alkyl chain role and helped to rationalize the
      significantly lower experimental MIC value observed for INH-C10. This compound
      seems to be able to counterbalance most of the conformational restrictions
      introduced by the mutation, which are thought to be responsible for the decrease
      in INH activity in the mutated strain. Therefore, INH-C10 appears to be a very
      promising lead compound for drug development. 

PMID- 25590861
TI  - Admixed origin of the Kayah (Red Karen) in Northern Thailand revealed by
      biparental and paternal markers.
AB  - This study analyzes the autosomal short tandem repeats (STRs) variation and the
      presence of Y chromosomal haplogroups from 44 individuals of the Kayah or Red
      Karen (KA) in Northern Thailand. The results based on autosomal STRs indicated
      that the KA exhibited closer genetic relatedness to populations from adjacent
      regions in Southeast Asia (SEA) than populations from Northeast Asia (NEA) and
      Tibet. Moreover, an admixed origin of the KA forming three population groups was
      observed: NEA, Southern China, and Northern Thailand. The NEA populations made a
      minor genetic contribution to the KA, while the rest came from populations
      speaking Sino-Tibetan (ST) languages from Southern China and Tai-Kadai (TK)
      speaking groups from Northern Thailand. The presence of six paternal haplogroups,
      composed of dual haplogroups prevalent in NEA (NO, N, and D1) and SEA (O2 and O3)
      as well as the intermediate genetic position of the KA between the SEA and NEA
      also indicated an admixed origin of male KA lineages. Our genetic results thus
      agree with findings in linguistics that Karenic languages are ST languages that
      became heavily influenced by TK during their southward spread. A result of the
      Mongol invasions during the 13th century A.D. is one possible explanation for
      genetic contribution of NEA to the KA.

PMID- 25590862
TI  - Novel amide and sulphonamide derivatives of 6-(piperazin-1-yl)phenanthridine as
      potent Mycobacterium tuberculosis H37Rv inhibitors.
AB  - A series of thirty three novel 6-(piperazin-1-yl)phenanthridine amide and
      sulphonamide analogues were synthesized, characterized and screened for their in
      vitro antimycobacterial activity against Mycobacterium tuberculosis (MTB) H37Rv
      strain. These compounds exhibited minimum inhibitory concentration (MIC) between
      1.56 and >=50 MUg/mL. Out of these derivatives, few compounds 6l, 6r, 7b, 7f, 7g
      and 7k exhibited moderate activity (MIC = 6.25 MUg/mL) and compounds 6b, 6e, 6k,
      6n, 7h, 7i and 7n displayed good activity (MIC = 3.13 MUg/mL), whereas compounds
      6m, 6s and 7d exhibited excellent anti-tubercular activity (MIC = 1.56 MUg/mL).
      In addition, MTT assay was accomplished on the active analogues of the series
      against mouse macrophage (RAW 264.7) cells to evaluate the toxicity profile of
      the newly synthesized compounds and selectivity index of the compounds was
      determined. Additionally, compounds 6b and 7d were docked to the ATPase domain of
      M. tuberculosis GyrB protein to know the interaction profile and structures of
      compounds 6b and 7d were further substantiated through single crystal XRD.

PMID- 25590863
TI  - Synthesis and bioevaluation of pyrazole-benzimidazolone hybrids as novel human 4
      Hydroxyphenylpyruvate dioxygenase inhibitors.
AB  - 4-Hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine
      catabolism, is an important target for treating type I tyrosinemia. Inhibition of
      HPPD can effectively alleviate the symptoms of type I tyrosinemia. However, only
      one commercial HPPD inhibitor, 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane
      1,3-dione (NTBC), has been available for clinical use so far. In the present
      study, a series of novel pyrazole-benzimidazolone hybrids were designed,
      synthesized and evaluated as potent human HPPD inhibitors. Most of the new
      compounds displayed significant inhibitory activity against the recombinant human
      HPPD. Moreover, compound 9l was identified as the most potent candidate with IC50
      value of 0.021 MUM against recombinant human HPPD, about 3-fold more potent than
      NTBC. Thus the pyrazole-benzimidazolone hybrid has great potential to be further
      developed for the treatment of type I tyrosinemia. 

PMID- 25590864
TI  - Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated
      chalcone natural products and their analogs.
AB  - Four natural chalcones bearing prenyl or geranyl groups, i.e., bavachalcone (1a),
      xanthoangelol (1b), isobavachalcone (1c), and isoxanthoangelol (1d) were
      synthesized by using a regio-selective iodination and the Suzuki coupling
      reaction as key steps. The first total synthesis of isoxanthoangelol (1d) was
      achieved in 36% overall yield. A series of diprenylated and digeranylated
      chalcone analogs were also synthesized by alkylation, regio-selective iodination,
      aldol condensation, Suzuki coupling and [1,3]-sigmatropic rearrangement. The
      structures of the 11 new derivatives were confirmed by (1)H NMR, (13)C NMR and
      HRMS. The anticancer activity of these new chalcone derivatives against human
      tumor cell line K562 were evaluated by MTT assay in vitro. SAR studies suggested
      that the 5'-prenylation/geranylation of the chalcones significantly enhance their
      cytotoxic activity. Among them, Bavachalcone (1a) displayed the most potent
      cytotoxic activity against K562 with IC50 value of 2.7 MUM. The morphology
      changes and annexin-V/PI staining studies suggested that those chalcone
      derivatives inhibited the proliferation of K562 cells by inducing apoptosis. 

PMID- 25590865
TI  - Trichinellosis surveillance--United States, 2008-2012.
AB  - PROBLEM/CONDITION: Trichinellosis is a parasitic disease caused by nematodes in
      the genus Trichinella, which are among the most widespread zoonotic pathogens
      globally. Infection occurs following consumption of raw or undercooked meat
      infected with Trichinella larvae. Clinical manifestations of the disease range
      from asymptomatic infection to fatal disease; the common signs and symptoms
      include eosinophilia, fever, periorbital edema, and myalgia. Trichinellosis
      surveillance has documented a steady decline in the reported incidence of the
      disease in the United States. In recent years, proportionally fewer cases have
      been associated with consumption of commercial pork products, and more are
      associated with meat from wild game such as bear. PERIOD COVERED: 2008-2012.
      DESCRIPTION OF SYSTEM: Trichinellosis has been a nationally notifiable disease in
      the United States since 1966 and is reportable in 48 states, New York City, and
      the District of Columbia. The purpose of national surveillance is to estimate
      incidence of infection, detect outbreaks, and guide prevention efforts. Cases are
      defined by clinical characteristics and the results of laboratory testing for
      evidence of Trichinella infection. Food exposure histories are obtained at the
      local level either at the point of care or through health department interview.
      States notify CDC of cases electronically through the National Notifiable Disease
      Surveillance System (available at http://wwwn.cdc.gov/nndss). In addition, states
      are asked to submit a standardized supplementary case report form that captures
      the clinical and epidemiologic information needed to meet the surveillance case
      definition. Reported cases are summarized weekly and annually in MMWR. RESULTS:
      During 2008-2012, a total of 90 cases of trichinellosis were reported to CDC from
      24 states and the District of Columbia. Six (7%) cases were excluded from
      analysis because a supplementary case report form was not submitted or the case
      did not meet the case definition. A total of 84 confirmed trichinellosis cases,
      including five outbreaks that comprised 40 cases, were analyzed and included in
      this report. During 2008-2012, the mean annual incidence of trichinellosis in the
      United States was 0.1 cases per 1 million population, with a median of 15 cases
      per year. Pork products were associated with 22 (26%) cases, including 10 (45%)
      that were linked with commercial pork products, six (27%) that were linked with
      wild boar, and one (5%) that was linked with home-raised swine; five (23%) were
      unspecified. Meats other than pork were associated with 45 (54%) cases, including
      41 (91%) that were linked with bear meat, two (4%) that were linked with deer
      meat, and two (4%) that were linked with ground beef. The source for 17 (20%)
      cases was unknown. Of the 51 patients for whom information was reported on the
      manner in which the meat product was cooked, 24 (47%) reported eating raw or
      undercooked meat. INTERPRETATION: The risk for Trichinella infection associated
      with commercial pork has decreased substantially in the United States since the
      1940s, when data collection on trichinellosis cases first began. However, the
      continued identification of cases related to both pork and nonpork sources
      indicates that public education about trichinellosis and the dangers of consuming
      raw or undercooked meat still is needed. PUBLIC HEALTH ACTIONS: Changes in
      domestic pork production and public health education regarding the safe
      preparation of pork have contributed to the reduction in the incidence of
      trichinellosis in the United States; however, consumption of wild game meat such
      as bear continues to be an important source of infection. Hunters and consumers
      of wild game meat should be educated about the risk associated with consumption
      of raw or undercooked meat.

PMID- 25590866
TI  - Cordycepin induces cell cycle arrest and apoptosis by inducing DNA damage and up
      regulation of p53 in Leukemia cells.
AB  - Cordycepin, an adenosine analog derived from Cordyceps militaris has been shown
      to exert anti-tumor activity in many ways. However, the mechanisms by which
      cordycepin contributes to the anti-tumor still obscure. Here our present work
      showed that cordycepin inhibits cell growth in NB-4 and U937 cells by inducing
      apoptosis. Further study showed that cordycepin increases the expression of p53
      which promotes the release of cytochrome c from mitochondria to the cytosol. The
      released cytochrome c can then activate caspase-9 and trigger intrinsic
      apoptosis. Cordycepin also blocks MAPK pathway by inhibiting the phosphorylation
      of ERK1/2, and thus sensitizes the apoptosis. In addition, our results showed
      that cordycepin inhibits the expression of cyclin A2, cyclin E, and CDK2, which
      leads to the accumulation of cells in S-phase. Moreover, our study showed that
      cordycepin induces DNA damage and causes degradation of Cdc25A, suggesting that
      cordycepin-induced S-phase arrest involves activation of Chk2-Cdc25A pathway. In
      conclusion, cordycepin-induced DNA damage initiates cell cycle arrest and
      apoptosis which leads to the growth inhibition of NB-4 and U937 cells. 

PMID- 25590867
TI  - A whole cell bioreporter approach to assess transport and bioavailability of
      organic contaminants in water unsaturated systems.
AB  - Bioavailability of contaminants is a prerequisite for their effective
      biodegradation in soil. The average bulk concentration of a contaminant, however,
      is not an appropriate measure for its availability; bioavailability rather
      depends on the dynamic interplay of potential mass transfer (flux) of a compound
      to a microbial cell and the capacity of the latter to degrade the compound. In
      water-unsaturated parts of the soil, mycelia have been shown to overcome
      bioavailability limitations by actively transporting and mobilizing organic
      compounds over the range of centimeters. Whereas the extent of mycelia-based
      transport can be quantified easily by chemical means, verification of the
      contaminant-bioavailability to bacterial cells requires a biological method.
      Addressing this constraint, we chose the PAH fluorene (FLU) as a model compound
      and developed a water unsaturated model microcosm linking a spatially separated
      FLU point source and the FLU degrading bioreporter bacterium Burkholderia
      sartisoli RP037-mChe by a mycelial network of Pythium ultimum. Since the
      bioreporter expresses eGFP in response of the PAH flux to the cell, bacterial FLU
      exposure and degradation could be monitored directly in the microcosms via
      confocal laser scanning microscopy (CLSM). CLSM and image analyses revealed a
      significant increase of the eGFP expression in the presence of P. ultimum
      compared to controls without mycelia or FLU thus indicating FLU bioavailability
      to bacteria after mycelia-mediated transport. CLSM results were supported by
      chemical analyses in identical microcosms. The developed microcosm proved
      suitable to investigate contaminant bioavailability and to concomitantly
      visualize the involved bacteria-mycelial interactions. 

PMID- 25590868
TI  - Complete thymectomy in adult rats with non-invasive endotracheal intubation.
AB  - Thymectomy in neonatal rodents is an established and reliable procedure for
      immunological studies. However, in adult rats, complications of hemorrhage and
      pneumothorax from pleural disruption can result in a significant mortality rate.
      This protocol is a simple method of rat thymectomy that utilizes a mini
      sternotomy and endotracheal intubation. Intubation is accomplished with a non
      invasive and easily reproducible method and allows for positive pressure
      ventilation to prevent pneumothorax and a controlled airway that allows
      sufficient time for careful thymus dissection to minimize pleural disruption. A
      1.5 cm sternal incision decreases contact with mediastinal vessels and pleura,
      while still providing full visualization of the thymus. Following exposure of the
      mediastinum, the thymus is removed by blunt dissection under magnification. The
      pleural space is then sealed by suture closure of the pre-tracheal muscles
      followed by the application of surgical glue. The thorax is then closed by suture
      closure of the sternum, followed by suture closure of the skin. All thymectomies
      were complete as evidenced by immunohistochemical (IHC) staining of mediastinal
      tissue, and absence of naive T-cells by flow cytometry, and the procedure had a
      96% survival rate. This method is suitable when complete thymectomy with minimal
      complications is desired for further immunological studies in athymic adult rats.

PMID- 25590869
TI  - Disentangling volumetric and hydrational properties of proteins.
AB  - We used molecular dynamics simulations of a typical monomeric protein, SNase, in
      combination with Voronoi-Delaunay tessellation to study and analyze the
      temperature dependence of the apparent volume, Vapp, of the solute. We show that
      the void volume, VB, created in the boundary region between solute and solvent,
      determines the temperature dependence of Vapp to a major extent. The less
      pronounced but still significant temperature dependence of the molecular volume
      of the solute, VM, is essentially the result of the expansivity of its internal
      voids, as the van der Waals contribution to VM is practically independent of
      temperature. Results for polypeptides of different chemical nature feature a
      similar temperature behavior, suggesting that the boundary/hydration contribution
      seems to be a universal part of the temperature dependence of Vapp. The results
      presented here shine new light on the discussion surrounding the physical basis
      for understanding and decomposing the volumetric properties of proteins and
      biomolecules in general. 

PMID- 25590870
TI  - Exosomal lipids impact on tumoral cell behavior.

PMID- 25590871
TI  - Isolation, characterization, and evaluation of bacterial root and nodule
      endophytes from chickpea cultivated in Northern India.
AB  - Endophytic bacteria from roots (12 isolates) and nodules (76 isolates) of
      chickpea legume grown under CCS Haryana Agricultural University farm were
      isolated. Among the endophytic bacteria, 50% from roots and 93.4% from nodules
      were Gram positive spore formers. Large number of endophytes from roots and
      nodules solubilized phosphate and produced ammonia. Isolate CRE3, and CNE215,
      were most efficient P solubilizers and. CRE12 and CNE76 being most efficient
      ammonia producer. Interestingly, few endophytic bacteria produced organic acid.
      Further selected 62 isolates were used to determine molecular diversity by RFLP
      of PCR amplified 16S rDNA. Endophytes from roots formed five separate clusters
      and nodule endophytes formed 13 clusters. Isolate CNE215 from nodules and CRE1
      from roots possessed multiple beneficial traits and belonged two different
      clusters. These two isolates were identified after amplification and sequencing
      of 16S rRNA gene. Isolate CNE215 showed more than 98% similarity with partial
      sequence of 16S rRNA gene of Bacillus subtilis, whereas CRE1 showed more than 98%
      similarity with Bacillus licheniformis. Efficacy of these two strains was
      evaluated under field conditions and an increase up to 22.5% in grain yield over
      uninoculated control was observed with B. subtilis strain CNE215, whereas all the
      recommended biofertilizers were able to record an increase upto 14.4%. 

PMID- 25590872
TI  - Calcium carbonate precipitation by strain Bacillus licheniformis AK01, newly
      isolated from loamy soil: a promising alternative for sealing cement-based
      materials.
AB  - The relevant experiments were designed to determine the ability of indigenous
      bacterial strains isolated from limestone caves, mineral springs, and loamy soils
      to induce calcium carbonate precipitation. Among all isolates examined in this
      study, an efficient carbonate-precipitating soil bacterium was selected from
      among the isolates and identified by 16S rRNA gene sequences as Bacillus
      licheniformis AK01. The ureolytic isolate was able to grow well on alkaline
      carbonate-precipitation medium and precipitate calcium carbonate more than 1 g L(
      1). Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD)
      analyses, and scanning electron microscopy (SEM)/energy-dispersive X-ray
      spectroscopy (EDX) examinations were performed in order to confirm the presence
      of calcium carbonate in the precipitate and to determine which polymorphs were
      present. The selected isolate was determined to be an appropriate candidate for
      application in a surface treatment of cement-based material to improve the
      properties of the mortar. Biodeposition of a layer of calcite on the surface of
      cement specimens resulted in filling in pore spaces. This could be an alternative
      method to improve the durability of the mortar. The kind of bacterial culture and
      medium composition had a profound impact on the resultant CaCO(3) crystal
      morphology.

PMID- 25590874
TI  - The role of nursing in health care.

PMID- 25590873
TI  - Diversity of ionizing radiation-resistant bacteria obtained from the Taklimakan
      Desert.
AB  - So far, little is known about the diversity of the radiation-resistant microbes
      of the hyperarid Taklimakan Desert. In this study, ionizing radiation (IR)
      resistant bacteria from two sites in Xinjiang were investigated. After exposing
      the arid (water content of 0.8 +/- 0.3%) and non-arid (water content of 21.3 +/-
      0.9%) sediment samples to IR of 3000 Gy using a (60)Co source, a total of 52
      gamma-radiation-resistant bacteria were isolated from the desert sample. The 16S
      rRNA genes of all isolates were sequenced. The phylogenetic tree places these
      isolates into five groups: Cytophaga-Flavobacterium-Bacteroides, Proteobacteria,
      Deinococcus-Thermus, Firmicutes, and Actinobacteria. Interestingly, this is the
      first report of radiation-resistant bacteria belonging to the genera Knoellia,
      Lysobacter, Nocardioides, Paracoccus, Pontibacter, Rufibacter and Microvirga. The
      16s rRNA genes of four isolates showed low sequence similarities to those of the
      published species. Phenotypic analysis showed that all bacteria in this study are
      able to produce catalase, suggesting that these bacteria possess reactive oxygen
      species (ROS)-scavenging enzymes. These radiation-resistant bacteria also
      displayed diverse metabolic properties. Moreover, their radiation resistances
      were found to differ. The diversity of the radiation-resistant bacteria in the
      desert provides further ecological support for the hypothesis that the ionizing
      radiation resistance phenotype is a consequence of the evolution of ROS
      scavenging systems that protect cells against oxidative damage caused by
      desiccation.

PMID- 25590875
TI  - [Nursing care as an ethical problem: concepts and principles applied to the act
      of caring].
AB  - In this paper the authors study the nature of the act of care, emphasize the
      importance of ethics in the professions related to the health of people and
      develop, in the light of the central tradition of Western moral philosophy, a set
      of principles that should guide nursing activity. 

PMID- 25590876
TI  - Interdisciplinarity and nursing research: opportunities and challenges.
AB  - Interdisciplinary collaboration is widely recognized and considered essential for
      optimizing the development of knowledge and practice. However,
      interdisciplinarity is commonly accepted as an unquestioned good; rarely examined
      as both a source of benefit as well as difficulty for nursing and other
      disciplines. The aim of this article is to critically examine the opportunities
      and challenges that interdisciplinarity can provide for research in nursing and
      other disciplines. Based on a North American perspective, I describe the
      emergence of uni-disciplinary nursing research and the knowledge exchanges that
      occurred between nursing and other disciplines. I discuss the rise of
      interdisciplinary research, outline several examples of nursing participation in
      interdisciplinarity, and highlight the prominent benefits and difficulties
      associated with interdisciplinary research. I argue that authentic collaboration
      is required to conduct meaningful interdisciplinary research and describe how
      this can be promoted. 

PMID- 25590877
TI  - [Sexual behaviors and practices of men who have sex with men].
AB  - The objective was to identify behaviors and sexual practices of men who have
      sexual relations with other men in the context of vulnerability to HIV/AIDS. This
      was a cross-sectional, exploratory and descriptive study. It was carried out in a
      gay sociability place in Fortaleza, Ceara, Brazil, between November 2010 and
      March 2011, through interviews with 189 men who have sex with men. The ethical
      aspects were respected. We found a sample consisting mostly by young, single, and
      highly educated men. The sexual history demonstrated the early onset of sexual
      activity, with a high prevalence of sexual intercourse with a partner of the
      opposite sex. There was also a high prevalence of HIV testing. Sexual practices
      revealed high prevalence of performing oral and anal sex, as well as high levels
      of protection in anal sex, despite the low protection in oral sex. A greater
      incorporation of prevention practices was found compared to the national scene in
      the beginning of the disease outbreak. 

PMID- 25590878
TI  - [Decision making satisfaction in health scale: instrument adapted and validated
      to Portuguese].
AB  - Decision making is an area of health research that has gained importance both for
      the partnership models of care that give prominence to the patient and family,
      either by growing concern about quality and customer satisfaction with the care
      provided. So we decided to make the cultural adaptation and to evaluate the
      psychometric properties of the Portuguese version "The Satisfaction with Decision
      Scale" de Holmes-Rovner (1996), which aims to assess satisfaction with the
      decisions taken in health. The sample consisted of 521 nursing students the
      School of Nursing of Porto. The results of reliability tests show good internal
      consistency for the total items (Alpha Cronbach = 0.88). The psychometric study
      allows us to state that the Portuguese version of "The Satisfaction with Decision
      Scale", we call "Escala da Satisfacao com a Decisao em Saude", is an instrument
      comparable with the original in terms of validity and reliability. 

PMID- 25590879
TI  - [Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in a hospital in
      Distrito Federal].
AB  - This study aimed to analyze demographic and clinical aspects of patients
      diagnosed with Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis
      (TEN), as well as identifying the actions of health professionals for the
      management of Adverse Drug Reactions (ADR) in a public hospital in Distrito
      Federal, Brazil. A descriptive and retrospective research was held, with
      quantitative approach. Data collected from all the records of 22 patients
      admitted with diagnosed with SJS and TEN, from January 2005 to September 2012.
      Data were analyzed using descriptive statistics. Of these cases, 9 were diagnosed
      with NET and 7, with SJS; there were more females (14); aged from 21 to 40 years
      (10); 21 were cured; the drugs more used were the antiepileptic ones (10).
      Fragility in clinical registers and in the actions to monitor the cases of ADR in
      this health service was observed. 

PMID- 25590880
TI  - [Elderly residents in homes for the aged: adjustment in the light of Callista
      Roy].
AB  - This study aimed to evaluate the adaptation of elderly individuals voluntarily
      reside in Institution for the Aged (LTCF) in the city of Fortaleza-CE, based on
      the theoretical model of Roy. Descriptive study, in a IPLI involving thirteen
      elderly residents. Data collect was through interviews in the months of October
      and December 2011 and organized by thematic content analysis. The following
      themes has emerged: I Physical subdivided into body sensation and body image;
      Staff and I, subdivided into self-consistency and auto ideal be moral-ethical
      spiritual. Thus, the option to live in ILPI not effectively changed the lives of
      elderly people. They managed to adapt to the local and coexist well with internal
      and external stimuli. 

PMID- 25590881
TI  - [Level of dependency and quality of life of elderly].
AB  - The quality of life (QoL) in older adults is largely determined by their
      functional status and health conditions. With the purpose of investigate the QoL
      and the factors affecting it, and identify the degree of dependency of the
      elderly was carried out an observational cross-sectional exploratory and
      descriptive, involving 93 elderly. In collecting data we used the Barthel Index
      and MOS SF-36. In the identification of levels of dependency results indicate us
      that 40.0% are independent and 18.0% are dependents, minimum being 12.0% total
      dependent. The results show us that, 88.0% of the subjects reported a score below
      50.0% on average reported a QoL of 39 +/- 10.0%. Checking that are a positive
      correlation between the degree of dependence and the index of QoL, especially in
      the physical component. It is therefore important to promote healthy aging in an
      attempt to favor the preservation of autonomy and functional capacity of the
      elderly.

PMID- 25590882
TI  - [The elderly care practices of indigenous-performance of health].
AB  - This research aims to understand the care practices of health professionals who
      assist the elderly Kaingang. It is a qualitative study, supported in ethnography,
      conducted by ten professionals working in primary health care in the indigenous
      land of Faxinal, Parana, Brazil. The data was collected from November 2010 to
      February 2012 by participant observation and interviews, and analyzed based on
      the Transcultural Care Theory. Was identified the preoccupation of the carers
      practices with the medication and immunization, as well as traditional medical
      care. To achieve these, care professionals had strategies that implemented
      maintenance of older people in care. We conclude that cultural values and
      integrate scientific need assistance to improve the health of elderly indigenous.

PMID- 25590883
TI  - [Nonverbal communication between nurses and the elderly based on the proxemics].
AB  - The aim is to analyze the nonverbal communication between nurses and the elderly
      in the nursing consultation based on the theory by Hall. The research concerns a
      descriptive exploratory study and it has a quantitative approach. It took place
      through filmings of the nursing consultations which happened in Health Basic
      Units in Joao Pessoa, Paraiba, Brazil, observed every minute, a total of 1.575
      nonverbal interactions. The analysis has showed the predominance of the female
      nurses (90.63%) and the elderly (65.63) and a regular classification for most of
      the factors as a prevalence of a sitting set (80.09), opposite chairs (64.46%),
      personal distance (91.40%), calm facial expression (59.78%), touch was used for a
      technical procedure (53.33%), visual interaction for the manipulation of the
      objects (57.69) and no alteration in the voice volume (48.79%). These results
      reflect the necessity of the nurses to domain consciously their corporal and
      facial manifestations in order to improve the interaction with the elderly. 

PMID- 25590884
TI  - [Blood transfusion receivers' perception of the transfusion process].
AB  - Qualitative research, descriptive exploratory, aimed to know the perception of
      blood transfusion recipients as to the process. The research was carried out at a
      blood bank in a city in southern Brazil, and the data were analyzed using the
      Collective Subject Discourse. Were interviewed using a semistructured instrument,
      eleven patients, men and women between 30 and 95 years, post-surgical recovery of
      cardiac surgery, underwent blood transfusion. Four central ideas emerged: loss
      and blood replacement; Preservation of life; Recognition of the transfusion
      process; and transfusion safety. The perception about the change that post
      transfusion begin to live from the transfusion process raises a reframing of life
      itself. This study showed that transfused patients perceive the transfusion
      process as a means of survival, and even having knowledge about the process and
      their meanings, there is the permanence of fears and anxieties that can be
      minimized by the multidisciplinary team. 

PMID- 25590885
TI  - [Identity of the resilient man in the context of ill with prostate cancer: a
      cultural perspective].
AB  - The study aimed to understand the context of resilient man when ill with prostate
      cancer. This is an ethnographic case study conducted with two prostate cancer
      survival men with a high degree of resilience. The data was collected on their
      places, in 2012 April and May, using semi-structured in-depth interviews,
      participant observation and ecomap. For the data analysis, it was built two units
      of meaning: "Identity of the resilient man: contextualizing the informants" and
      "The resilient man finding himself ill". It was noticed that the identity of
      being a resilient man, to these informants, was marked by historical and cultural
      difference which permeated their actions in the process of being ill with
      prostate cancer. It is important that nurses pay attention to the cultural
      aspects of human health, so that they can feel part of the healing process,
      becoming an active subject facing their own health. 

PMID- 25590886
TI  - [Perception of nurses on the use of computer at the work].
AB  - The objective of this study was to apprehend the perception nurses have on the
      use of computer in the hospital environment. Took part in the study 14 nurses of
      a public hospital. Collection of data took place through recorded interview and
      Field Diary. Data was analyzed according to Content Analysis technique. Six
      thematic categories emerged from the interviews such as the one that approached
      the positive aspects: speed, legibility and accuracy of the information;
      patients' safety and; improvements in the quality of care. Among the negative
      aspects copy and paste the Medical Prescriptions and Nursing; lack of computers
      and the nurse distancing to the patient were highlighted. In spite of the
      fragilities, they were all in favor of the use of computer technology at the work
      and they pointed it as indispensable resource to the quality of care. 

PMID- 25590887
TI  - [Parents' needs and concerns at different stages of the life cycle].
AB  - OBJECTIVE: this study aimed to identify priority needs and concerns expressed by
      fathers in the performance of their role in three stages of the life cycle:
      adolescence, productive age, and mature age. METHODOLOGY: this is an exploratory
      study with a qualitative approach, conducted with fourteen fathers residing in a
      municipality in the extreme south of Brazil. The data were collected between May
      and August 2011 by means of the in-depth interview. Through the technique of
      written discourse analysis and the array built upon Bronfenbrenner's
      bioecological theory, we obtained three categories: fathers' needs/concerns,
      generated in their relationship with the world of work; needs/concerns that
      emerged from the relationship of care with the children; and fathers' concerns
      about the future of the children. CONCLUSIONS: we identified that the concern
      with the future of the children was pointed out by fathers of all age groups
      investigated.

PMID- 25590888
TI  - [Eating habits in the first year of life: social representations of young
      mothers].
AB  - This is qualitative research that investigates the social representations of
      adolescent mothers on child eating habits in the first year of life. Its subjects
      were 10 adolescent mothers, whose children were aged seven to twelve months. Data
      were collected through semi-structured interview, besides the use of visual
      material. The analysis followed the technique of content analysis, relying on the
      framework of Social Representations Theory. That analysis revealed four themes:
      the conflict of breastfeeding versus consecration of porridge; establishing
      complementary feeding of the child; crystallized speech: "yogurt is better than a
      little steak"; the (un)definition of maternal eating habits: implications for
      infant feeding. The representations that drive maternal practices in selecting,
      preparing and offering food follow a particular logic, where adolescents
      reinterpret technical speeches in terms of their culture. 

PMID- 25590889
TI  - [Cross-Mapping: diagnostic labels formulated according to the ICNP(r) versus
      diagnosis of NANDA International].
AB  - This descriptive study aimed at elaborating nursing diagnostic labels according
      to ICNP(r); conducting a cross-mapping between the diagnostic formulations and
      the diagnostic labels of NANDA-I; identifying the diagnostic labels thus obtained
      that were also listed in the NANDA-I; and mapping them according to Basic Human
      Needs. The workshop technique was applied to 32 intensive care nurses, the cross
      mapping and validation based on agreement with experts. The workshop produced
      1665 diagnostic labels which were further refined into 120 labels. They were then
      submitted to a cross-mapping process with both NANDA-I diagnostic labels and the
      Basic Human Needs. The mapping results underwent content validation by two expert
      nurses leading to concordance rates of 92% and 100%. It was found that 63 labels
      were listed in NANDA-I and 47 were not. 

PMID- 25590890
TI  - [Self-care in family caregiver of dependent adults or elderly persons after
      hospital discharge].
AB  - This article presents an understanding concerning self-care in family caregivers
      according to Dorothea Orem's theory. Resulting from a qualitative research based
      on Grounded Theory, this work uses the techniques of home visiting, field notes
      and semistructured interviews with 11 caregivers after the hospitalization of a
      family member in a teaching Hospital located in Minas Gerais. Four categories
      were found and among them a central category is highlighted from which some
      facilities, difficulties and strategies for selfcare in caregiver were analyzed.
      Considering the difficulties, insufficient time for healthcare was noticed
      whereas the support from other family members appeared as a facility. The main
      strategies were: faith as a support; shift work in healthcare and community
      resources. This study demonstrated that hospital discharge guidelines and nursing
      follow-up after discharge were responsible for positive contributions to self
      care in caregivers helping them to overcome their difficulties and enhancing
      their potentialities. 

PMID- 25590891
TI  - [Adenosine triphosphate bioluminescence to evaluate the effectiveness of surface
      cleaning: an integrative review].
AB  - OBJECTIVE: To identify indications and controversies in the literature of the use
      of ATP bioluminescence to evaluate the effectiveness of surface cleaning in
      healthcare facilities. METHOD: Integrative literature review between 2000 and
      2012 in the following databases: MEDLINE, LILACS, Science Direct, SCOPUS and Isi
      Web of Knowledge. RESULTS: were selected for this review 15 articles. The ATP
      bioluminescence was considered an important educational resource and
      complementary method to visual inspection and microbiological evaluation of the
      effectiveness of cleaning. The impossibility to indicate surface contamination by
      microorganisms, interference by chemicals and the difficulty of interpreting the
      results constitute the main controversies in the use of ATP in health services.
      CONCLUSION: Although this is an important resource in the evaluation of surface
      cleaning, more studies are necessary for effective incorporation of the method in
      health services.

PMID- 25590892
TI  - [A creative and sensitive way to research].
AB  - This experience report describes the application of Creative Sensitive Method in
      a qualitative exploratory-descriptive research. Its theoretical foundation and
      the way this method was applied objectively presented through the following
      stages: introduction, production, presentation, discussion and evaluation.
      Finally, one can argue that the method, among others pathways, is a good
      alternative methodology for generating data in collective spaces for application
      in qualitative research related to nursing or others health contexts. 

PMID- 25590893
TI  - [History of the child's health: conquers, policies and perspectives].
AB  - The aim of this study was describing and reflecting about the aspects related to
      the social history and public policies for the children's health assistance in
      Brazil. A brief historical contextualization was realized concerning changes on
      the way the society views the child in Brazil and around the world, also
      perspectives considering public policies for the children's health in the
      national context were presented. It was possible to identify that the historical
      evolution of the child participation in the society is linked to the changes in
      the assistance public policies, which were demonstrated in the child death
      decrease and associated to challenges, like the morbimortality reduction caused
      by perinatal injuries and avoidable causes. The advances and conquers in the
      child's health are evolved in a paradigmatic change movement into a model of a
      net formation and a comprehensiveness care. This context requires the human
      resources preparation for such area, based on the health promotion and
      prevention, as well as a better quality of life of the population. 

PMID- 25590894
TI  - [The prenatal care program in Primary Care in Portugal - a reflection].
AB  - The quality improvement of care provided to the pregnant women and newborn is one
      of the priority areas for intervention of the National Health Plan. While
      acknowledging that the measures introduced in recent years have contributed to
      lower the values of maternal and perinatal mortality, it should also be mentioned
      that unplanned pregnancies continue to occur, and that they often result in a
      delayed or absent prenatal surveillance. In this paper, we seek to reflect on the
      prenatal surveillance program under Primary Health Care relating to quality of
      health care provided in the context of reproductive health. We concluded that
      prenatal surveillance includes a set of specific care services targeted at a
      vulnerable group, constituting an important and susceptible area of evaluation in
      primary care. 

PMID- 25590896
TI  - One-step electroplating porous graphene oxide electrodes of supercapacitors for
      ultrahigh capacitance and energy density.
AB  - An electroplating method was used for the first time to synthesize 3D porous
      graphene oxide (PGO) architectures, exhibiting ultrahigh capacitance and energy
      density as electrodes of supercapacitors. Scanning electron microscopy
      illustrated the porous structures which promoted the stability and alleviated the
      stacking of the graphene oxide layers. As investigated in a three-electrode
      supercapacitor cell, PGO electrodes exhibited the maximum capacitance and energy
      of 973 F . g(-1) and 98.4 Wh . Kg(-1), which are better than current reports and
      comparable to batteries. At 4 A . g(-1) for high-power applications, PGO
      electrodes reached a capacitance, energy, and power density of 493 F . g(-1),
      49.9 Wh . Kg(-1), and 1700 W . Kg(-1), and they retained ~97.83% of capacitance
      after 10 000 charge/discharge processes. Furthermore, when the PGO was bent
      exaggeratedly, it still displayed identical properties, which is of important
      significance for supporting wearable devices. 

PMID- 25590895
TI  - Effects of Aspergillus species inoculation and their enzymatic activities on the
      formation of volatile components in fermented soybean paste (doenjang).
AB  - The volatile components of rice-koji doenjang produced in association with
      various Aspergillus species (A. oryzae, A. sojae, and A. kawachii) during 8 weeks
      of fermentation were compared using gas chromatography-mass spectrometry analysis
      and multivariate statistical analysis. In addition, the activities of diverse
      enzymes (alpha-amylase, protease, lipase, and esterase) were determined to
      investigate their effects on the formation of volatile compounds. Regardless of
      the fungi types, carbonyls including 4-methylheptan-2-one, heptan-2-one, (E)-hept
      2-enal, and hexanal were found to contribute mainly to early phase fermentation,
      whereas the contents of ethyl esters of long-chained fatty acids were
      considerably enhanced in the latter stage of fermentation. With the exception of
      alpha-amylase, the activities of the studied enzymes generally increased as
      fermentation proceeded, and there were significant differences in enzymes
      activities between the species of fungi. The lipase activity was strongly
      correlated with the formation of long-chain fatty acid esters, which could be
      related to the distinctive organoleptic properties of rice-koji doenjang.

PMID- 25590897
TI  - Disorder-to-order transition of MAGI-1 PDZ1 C-terminal extension upon peptide
      binding: thermodynamic and dynamic insights.
AB  - PDZ domains are highly abundant protein-protein interaction modules commonly
      found in multidomain scaffold proteins. The PDZ1 domain of MAGI-1, a protein
      present at cellular tight junctions that contains six PDZ domains, is targeted by
      the E6 oncoprotein of the high-risk human papilloma virus. Thermodynamic and
      dynamic studies using complementary isothermal titration calorimetry and nuclear
      magnetic resonance (NMR) (15)N heteronuclear relaxation measurements were
      conducted at different temperatures to decipher the molecular mechanism of this
      interaction. Binding of E6 peptides to the MAGI-1 PDZ1 domain is accompanied by
      an unusually large and negative change in heat capacity (DeltaC(p)) that is
      attributed to a disorder-to-order transition of the C-terminal extension of the
      PDZ1 domain upon E6 binding. Analysis of temperature-dependent thermodynamic
      parameters and (15)N NMR relaxation data of a PDZ1 mutant in which this disorder
      to-order transition was abolished allows the unusual thermodynamic signature of
      E6 binding to be correlated to local folding of the PDZ1 C-terminal extension.
      Comparison of the exchange contributions observed for wild-type and mutant
      proteins explains how variation in the solvent-exposed area may compensate for
      the loss of conformational entropy and further designates a distinct set of a few
      residues that mediate this local folding phenomena.

PMID- 25590898
TI  - Healable luminescent self-assembly supramolecular metallogels possessing
      lanthanide (Eu/Tb) dependent rheological and morphological properties.
AB  - Herein we present the use of lanthanide directed self-assembly formation (Ln(III)
      = Eu(III), Tb(III)) in the generation of luminescent supramolecular polymers,
      that when swelled with methanol give rise to self-healing supramolecular gels.
      These were analyzed by using luminescent and (1)H NMR titrations studies,
      allowing for the identification of the various species involved in the subsequent
      Ln(III)-gel formation. These highly luminescent gels could be mixed to give a
      variety of luminescent colors depending on their Eu(III):Tb(III) stoichiometric
      ratios. Imaging and rheological studies showed that these gels prepared using
      only Eu(III) or only Tb(III) have different morphological and rheological
      properties, that are also different from those determined upon forming gels by
      mixing of Eu(III) and Tb(III) gels. Hence, our results demonstrate for the first
      time the crucial role the lanthanide ions play in the supramolecular
      polymerization process, which is in principle a host-guest interaction, and
      consequently in the self-healing properties of the corresponding gels, which are
      dictated by the same host-guest interactions. 

PMID- 25590899
TI  - Embedding cognizance in intellectual development.
AB  - This study examined whether cognizance of cognitive processes (i.e., awareness of
      the perceptual and inferential origins of knowledge) mediates between basic
      processing efficiency functions (i.e., processing speed, attention control, and
      working memory) and fluid cognition (e.g., performance on Raven-like matrices)
      during development. For this aim, children from 4 to 8 years of age were examined
      by various measures addressed to each of these processes. All processes developed
      systematically throughout this age period. Structural equation modeling showed
      that awareness does have this mediating role, that this mediation is phase
      specific based on perceptual awareness and theory of mind during the 5- and 6
      year phase and on inferential awareness during the 7- and 8-year phase, and that
      it builds up within each developmental cycle. Attention control emerges from,
      rather than directs, working memory and largely remains beyond awareness through
      the age span studied. Implications for theory of intellectual development are
      discussed.

PMID- 25590901
TI  - Editorial.

PMID- 25590900
TI  - Infant auditory short-term memory for non-linguistic sounds.
AB  - This research explores auditory short-term memory (STM) capacity for non
      linguistic sounds in 10-month-old infants. Infants were presented with auditory
      streams composed of repeating sequences of either 2 or 4 unique instruments
      (e.g., flute, piano, cello; 350 or 700 ms in duration) followed by a 500-ms
      retention interval. These instrument sequences either stayed the same for every
      repetition (Constant) or changed by 1 instrument per sequence (Varying). Using
      the head-turn preference procedure, infant listening durations were recorded for
      each stream type (2- or 4-instrument sequences composed of 350- or 700-ms notes).
      Preference for the Varying stream was taken as evidence of auditory STM because
      detection of the novel instrument required memory for all of the instruments in a
      given sequence. Results demonstrate that infants listened longer to Varying
      streams for 2-instrument sequences, but not 4-instrument sequences, composed of
      350-ms notes (Experiment 1), although this effect did not hold when note
      durations were increased to 700 ms (Experiment 2). Experiment 3 replicates and
      extends results from Experiments 1 and 2 and provides support for a duration
      account of capacity limits in infant auditory STM.

PMID- 25590902
TI  - Cross-cultural adaptation of Preschool Language Assessment Instrument: Second
      Edition.
AB  - PURPOSE: In Brazil, formal tools for the evaluation of spoken language are
      scarce. Therefore, this study aimed to translate and adapt to Brazilian
      Portuguese the Preschool Language Assessment Instrument: Second Edition (PLAI-2).
      METHODS: The process of translation and adaptation of this instrument was
      conducted in two stages - Stage 1: (1a) translation of the original version to
      Brazilian Portuguese, (1b) comparison of the translated versions and synthesis
      into a single Portuguese version, (1c) back-translation, (1d) revision of the
      translated version; and Step 2: (2a) application of the Portuguese version in a
      pilot project with 30 subjects, and (2b) statistical comparison of three age
      groups. RESULTS: In the Brazilian version, all items of the original version were
      kept. However, it was necessary to modify the application order of one item, and
      the change of one picture was suggested in another. The results obtained after
      application indicated that the Brazilian version of the PLAI-2 allows us to
      distinguish the performance of participants belonging to different age groups,
      and that the raw score tends to increase with age. CONCLUSION: Semantic and
      syntactic adjustments were required and made to ensure that PLAI-2 would be used
      with the same methodological rigor of the original instrument. The adaptation
      process observed the theoretical, semantic, and cultural equivalences.

PMID- 25590903
TI  - Phonological and semantic verbal fluency: a comparative study in hearing-impaired
      and normal-hearing people.
AB  - PURPOSE: To compare the performance of hearing-impaired and normal-hearing people
      on phonologic and semantic verbal fluency tests. METHODS: A cross-sectional study
      was conducted with 48 hearing-impaired adults and 42 individuals (control group)
      with no hearing or language complaints. Sociodemographic data were collected, as
      well as the characteristics of hearing loss and of the electronic auditory device
      (hearing aids or cochlear implant), when relevant. Verbal fluency was tested in
      two different tasks: by semantic category (animals) and by phonology (letter F).
      RESULTS: Educational level has influenced the results of fluency tests in both
      groups, with more evidence in the hearing-impaired subjects (p<0.001). Hearing
      impaired subjects showed worse performance in verbal fluency tests when compared
      to normal-hearing people in groups with up to 10 years of schooling. In the
      comparison of performance in the two tests, both groups showed better results in
      the semantic fluency task. CONCLUSION: The hearing-impaired subjects with low
      educational level evoked fewer words in semantic and phonologic verbal fluency
      tests in comparison to normal-hearing subjects. Educational level is a relevant
      issue to the study of verbal fluency in deaf and hearing-impaired people.

PMID- 25590904
TI  - School-age children with specific language impairment produce more speech
      disfluencies than their peers.
AB  - PURPOSE: To compare the occurrence of speech disfluencies during narrative
      production in children with specific language impairment (SLI) and their age
      matched peers. METHODS: The study included 60 children aged between 7 and 10
      years, 40 with typical language development and 20 with SLI. For data collection,
      a series of 15 stories was used, each one represented by pictures composed of
      four scenes. Narratives were transcripted and the speech disfluencies presented
      on them were classified as stuttering-like disfluencies (part-word repetition,
      single-syllable word repetition, and dysrhythmic phonation - prolongations,
      blocks and broken words) or other disfluencies (interjection, revision/abandoned
      utterances, and multisyllable/phrase repetition). The disfluency categories were
      compared in each group and its occurrence was also compared between groups.
      RESULTS: The occurrence of stuttering-like and other disfluencies did not differ
      among children with typical language development, whereas children with SLI
      produced other disfluencies. Between-group comparison showed that children with
      SLI produced more disfluencies of both types than their age-matched peers.
      CONCLUSION: Children with SLI showed more speech disfluencies during narrative
      production than their age-matched peers, and the most common disfluencies used by
      them were not typical of people who stutter (interjection, revision/abandoned
      utterances, and multisyllable/phrase repetition).

PMID- 25590905
TI  - Fluency profile: comparison between Brazilian and European Portuguese speakers.
AB  - The purpose of the study was to compare the speech fluency of Brazilian
      Portuguese speakers with that of European Portuguese speakers. The study
      participants were 76 individuals of any ethnicity or skin color aged 18-29 years.
      Of the participants, 38 lived in Brazil and 38 in Portugal. Speech samples from
      all participants were obtained and analyzed according to the variables of
      typology and frequency of speech disruptions and speech rate. Descriptive and
      inferential statistical analyses were performed to assess the association between
      the fluency profile and linguistic variant variables. We found that the speech
      rate of European Portuguese speakers was higher than the speech rate of Brazilian
      Portuguese speakers in words per minute (p=0.004). The qualitative distribution
      of the typology of common dysfluencies (p<0.001) also discriminated between the
      linguistic variants. While a speech fluency profile of European Portuguese
      speakers is not available, speech therapists in Portugal can use the same speech
      fluency assessment as has been used in Brazil to establish a diagnosis of
      stuttering, especially in regard to typical and stuttering dysfluencies, with
      care taken when evaluating the speech rate.

PMID- 25590906
TI  - Correlation between sleep and quality of life in cerebral palsy.
AB  - PURPOSE: To investigate and correlate the sleep pattern and quality of life in
      individuals with cerebral palsy (CP) compared to healthy controls. METHODS:
      Seventy-eight subjects (aged 4-18 years, both genders) comprised two groups: CP,
      composed of 43 individuals with CP, and control, composed of 35 individuals
      without neurodevelopmental disorders. General Sleep Habits Questionnaire, Sleep
      Disturbance Scale for Children, sleep diary, Child Health Questionnaire, and
      Children's Quality of Life Scale were used. RESULTS: This study identified that
      60.5% individuals with CP had sleep disorders. The respiratory disorders (25.6%)
      and the sleep hyperhidrosis (34.9%) were the most common disturbances in the
      group with CP. Moreover, 23.2% individuals of the group with CP reported awaking
      in the middle of the night and 37.2% of them snore, both percentages were higher
      than those in the control group. The sleep diary showed that individuals in the
      group with CP spend more time to initiate sleep (around 21 minutes). The group
      with CP also showed deficits in all parameters analyzed by the Child Health
      Questionnaire, except in family activity and the sleep-wake pattern, and quality
      of life showed negative correlation in several respects. CONCLUSION: The altered
      pattern of sleep in individuals with CP directly affects their physical and
      emotional well-being.

PMID- 25590907
TI  - Verification of the therapeutic process in cleft patients.
AB  - PURPOSE: This study was conducted to verify the origin of a longer or even failed
      therapeutic process in patients with cleft lip and palate as to its difficulty.
      METHODS: Eighteen children undergoing therapeutic process were observed for at
      least 6 months and divided into two groups: presenting isolated cleft lip and
      palate (group I) and having been diagnosed by a Speech-Language Pathologist with
      reading and writing disorders, with manifestation of phonological awareness
      deficit (group II). Two tests were applied for the evaluation of speech and
      language: ABFW Language Test for Young Children (phonology) and Phonological
      Awareness: Instrument of Sequential Assessment (CONFIAS). RESULTS: Group I
      presented higher percentages in ABFW test than group II, except in the
      "simplification of consonant cluster" and "plosive devoicing" variables. It was
      also observed that, in the process of omission, group I hardly omits the vibrant
      consonant, as observed in group II. At the syllable level of CONFIAS, the
      percentages observed in group I tended to be higher than in group II, with the
      exception of the following tasks: "medial syllable," "production of rhyme," and
      "exclusion." At the phoneme level, the percentages observed in group II tended to
      be higher than in group I, with the exception of the following tasks: "starts
      with given sound," "exclusion," "synthesis," and "segmentation." No significant
      difference was observed between percentage distributions in groups I and II
      (p>0.118). CONCLUSIONS: The differences found between groups I and II, although
      not statistically significant, may suggest that the presence of malformation
      hinders speech and language acquisition and development and prolongs the
      therapeutic process if directive interventions are not carried out, including
      phonological awareness therapy.

PMID- 25590908
TI  - Myofunctional orofacial examination: comparative analysis in young adults with
      and without complaints.
AB  - PURPOSE: To verify myofunctional orofacial characteristics in young adults and to
      compare data on individuals with and without myofunctional complaints, aiming to
      identify the main myofunctional problems and differentiating them from
      characteristics that are common for this population, as well as to list items for
      myofunctional evaluation in this population. METHODS: Cross-sectional study with
      85 adult participants, aged between 19 and 39 years, selected through consecutive
      sampling at the Department of Speech, Language and Hearing Sciences of
      Universidade Veiga de Almeida. The participants were divided into two groups: G1
      (comprising 50 individuals referred for orofacial myofunctional disorders) and G2
      (comprising 35 volunteers without complaints). Descriptive evaluation of
      craniofacial structures of hard and soft tissues, kinesiology and mandible range
      of motion and functional patterns of breathing, chewing, and swallowing was
      applied. Three expert Speech-Language pathologists assessed all participants.
      Statistical analysis was done using chi2-test, Student's t-test, or Mann-Whitney
      test. The reliability level was 99%. RESULTS: A predominance of Angle Class I
      pattern of occlusions for G2 (p<0.0001) was found. G1 showed (p<0.0001) mandible
      movements with deviations and joint noises, amplitude reduction in lateral and
      protrusive movements, unilateral chewing, nonexpected muscle contraction,
      temporomandibular joint noises, swallowing with excessive contraction of the
      orbicularis oris muscle, loud noise, and residues (p=0.006). CONCLUSION: The main
      myofunctional orofacial alterations in young adults with complaints refer to
      changes of the mandibular movements and patterns of chewing or of swallowing,
      reflecting the main items of the clinical evaluation. Many items of assessment
      and characterization do not differ between the groups, and these should be
      analyzed regarding their relevance.

PMID- 25590909
TI  - Correlation between the reason for referral, clinical, and objective assessment
      of the risk for dysphagia.
AB  - PURPOSE: To correlate the reason for referral to speech therapy service at a
      university hospital with the results of clinical and objective assessment of risk
      for dysphagia. METHODS: This is a cross-sectional, observational, retrospective
      analytical and quantitative study. The data were gathered from the database, and
      the information used was the reason for referral to speech therapy service,
      results of clinical assessment of the risk for dysphagia, and also from
      swallowing videofluoroscopy. RESULTS: There was a mean difference between the
      variables of the reason for the referral, results of the clinical and objective
      swallowing assessments, and scale of penetration/aspiration, although the values
      were not statistically significant. Statistically significant correlation was
      observed between clinical and objective assessments and the penetration scale,
      with the largest occurring between the results of objective assessment and
      penetration scale. CONCLUSION: There was a correlation between clinical and
      objective assessments of swallowing and mean difference between the variables of
      the reason for the referral with their respective assessment. This shows the
      importance of the association between the data of patient's history and results
      of clinical evaluation and complementary tests, such as videofluoroscopy, for
      correct identification of the swallowing disorders, being important to combine
      the use of severity scales of penetration/aspiration for diagnosis.

PMID- 25590910
TI  - Evaluation of the location of capsules swallowed with food during the pharyngeal
      phase triggering in asymptomatic adults.
AB  - OBJECTIVE: To assess the location of hard gelatin capsules in the pharyngeal
      phase triggering among asymptomatic adults. INTRODUCTION: The location of the
      bolus during the pharyngeal phase triggering provides information about the
      sensorimotor model of the beginning of deglutition onset. PURPOSE: To evaluate
      the location of hard gelatin capsules in the pharyngeal phase triggering among
      asymptomatic adults. METHODS: A videofluoroscopy swallowing study was carried out
      in 60 subjects (14 male and 46 female participants) aged between 27 and 55 years,
      who were evaluated with hard gelatin capsules #00 and #3 containing barium
      sulfate, swallowed with liquid food and pudding, in free volume. The first
      laryngeal elevation movement was the criterion to locate the pharyngeal phase
      triggering. Statistical analysis was based on the McNemar test. RESULTS: Capsule
      #3 presented higher percentage of location in the tongue dorsum compared to
      capsule #00, and capsule #00 presented higher percentage of location in the
      tongue base and vallecula compared to capsule #3. There was a difference between
      different capsules swallowed with liquid (p=0.016) and pudding (p=0.037).
      CONCLUSION: The capsule size influenced the location of the pharyngeal phase
      triggering. Smaller capsules started pharyngeal phase in the most anterior region
      (tongue dorsum) compared to larger capsules.

PMID- 25590911
TI  - Remote programming of cochlear implants.
AB  - PURPOSE: To verify the effectiveness of remote programming of cochlear implants
      by stimulation levels and results in the perception of speech and free-field
      audiometry tests. METHODS: Twelve patients from both genders, aged between 18 and
      59 years, users of internal cochlear implant and speech processor of the same
      model for at least 12 months, were selected. Both the remote programming (RP) and
      the live programming (LP) were performed on the same day, measuring the minimum
      (T) and maximum (C) stimulation levels of five electrodes with the interpolation
      of the remaining ones. Speech perception tests were applied using 65 dBSPL
      (recorded open context sentences and monosyllables). The patients were submitted
      to free-field audiometry at 250-8,000 Hz frequencies. The results for the RP and
      LP were compared. RESULTS: Differences in mean of the T levels for three
      electrodes and the C levels for one electrode were found. No difference between
      the results was obtained in the speech perception tests and audiometric
      thresholds in the RP and LP. CONCLUSION: The RP is a simple and effective
      procedure for programming cochlear implant devices and, although there were
      differences in the stimulation levels of some electrodes, it did not interfere in
      the speech perception outcomes.

PMID- 25590912
TI  - Parental perspectives of children using cochlear implant.
AB  - PURPOSE: To evaluate the parents' perspective with regard to evolution of their
      child with cochlear implant (CI). METHODS: This was a cross-sectional prospective
      study conducted at the Centro de Pesquisas Audiologicas of Hospital de
      Reabilitacao de Anomalias Craniofaciais of Universidade de Sao Paulo. The
      selection of the sample was performed from the spontaneous demand, among the
      months from July to December 2011. The final sample comprised 50 parents or
      guardians of children using CI, with minimum 1 year and maximum of 3 years of
      device use. The translated and adapted to Brazilian Portuguese version of the
      questionnaire "Perspectives of parents of children with cochlear implants" was
      applied. This instrument consists of 74 questions and allows quantification of
      the parents' perspective on subscales that illustrate the situation of the child
      and family. Each question has five options scored from one to five responses. The
      Spearman test for comparison of results between the subscales was applied.
      RESULTS: The social relationships, self-sufficiency, and communication subscales
      showed the highest mean score, whereas the worst score was for child support
      subscale, reflecting the independence and autonomy of the patients. The
      correlation between the child subscales was realized, and the results showed
      themselves significant and positive for communication subscale of communication
      with all others subscales. The family subscales also had a positive correlation
      with the communication, education, and self-sufficiency. CONCLUSION: These
      results demonstrate that parents have good expectations regarding communication,
      independence, and social participation of children after CI surgery, and this
      questionnaire is a useful tool for use in clinical practice.

PMID- 25590913
TI  - Auditory temporal abilities in children with history of recurrent otitis media in
      the first years of life and persistent in preschool and school ages.
AB  - PURPOSE: To study the temporal auditory ordering and resolution abilities in
      children with and without a history of early OME and ROME, as well as to study
      the responses according to age. METHODS: A total of 59 children were evaluated,
      and all of them presented pure tone thresholds within the normal range at the
      time of the conduction of the hearing tests. The children were divided into two
      groups according to the occurrence of episodes of recurrent otitis media. Then,
      each group was divided into two subgroups according to age: 7- and 8-year olds,
      and 9- and 10-year olds. All children were assessed with standard tests of
      temporal frequency (ordination) and gaps-in-noise (resolution). RESULTS: For the
      temporal abilities studied, children with a history of otitis media presented
      significantly lower results compared to the control group. In the frequency
      pattern test, the correct answers increased with age in both groups. In the
      identification of silence intervals, the control group showed no change in
      threshold regarding to age, but this change was present in the group with a
      history of otitis media. CONCLUSION: Episodes of otitis media with effusion in
      the first year of life, recurrent and persistent in preschool and school ages,
      negatively influence the temporal ordering and resolution abilities.

PMID- 25590914
TI  - Cognitive Vocal Program applied to individuals with signals presbylarynx:
      preliminary results.
AB  - PURPOSE: To propose and verify the feasibility of a vocal program intervention in
      patients with presbylarynx signs with or without vocal complaints. METHOD: Among
      20 elder participants of the current research, 3 female patients with median age
      of 67 years were chosen for the pilot study. Laryngological examination, vocal
      recording with CAPE-V (Consensus Auditory-Perceptual Evaluation of Voice)
      protocol, and Screening Protocol of Risk of Dysphonia (SPRD) were conducted
      before and after the program intervention. They joined the Cognitive Vocal
      Program for presbyphonia based on the genetic epistemology by Jean Piaget
      associated with vocal techniques based on scientific literature. This program is
      structured with six sessions and each one of them is focused in different aspects
      of vocal production. RESULTS: After the program intervention, some aspects such
      as loudness, coordination between breathing and speaking, accuracy in
      articulatory movements, jitter, and harmonics-to-noise ratio improved with
      parameters within the expected range for the age group. Three female participants
      were observed for better vocal quality, higher fundamental frequency, and better
      maximum phonation time. In two cases, tension related to loudness elevation and
      better scores on SPRD was observed. Using by high-speed laryngeal image, we also
      observed reduction of presbylarynx signs, and remarkable improvement in glottis
      closure competence and mucosal wave movement of the patients with and without
      vocal complaints. CONCLUSION: The preliminary results suggest encouraging
      prospects for the proposal with improvement in the aspects analyzed. This program
      was well designed and did not require any further adjustments.

PMID- 25590915
TI  - Phonological processing deficits as a universal model for dyslexia: evidence from
      different orthographies.
AB  - PURPOSE: To verify the universal nature of the phonological processing deficit
      hypothesis for dyslexia, since the most influential studies on the topic were
      conducted in children or adults speakers of English. RESEARCH STRATEGY: A
      systematic review was designed, conducted and analyzed using PubMed, Science
      Direct, and SciELO databases. SELECTION CRITERIA: The literature search was
      conducted using the terms "phonological processing" AND "dyslexia" in
      publications of the last ten years (2004-2014). DATA ANALYSIS: Following
      screening of (a) titles and abstracts and (b) full papers, 187 articles were
      identified as meeting the pre-established inclusion criteria. RESULTS: The
      phonological processing deficit hypothesis was explored in studies involving
      several languages. More importantly, we identify studies in all types of writing
      systems such as ideographic, syllabic and logographic, as well as alphabetic
      orthography, with different levels of orthography-phonology consistency.
      CONCLUSION: The phonological processing hypothesis was considered as a valid
      explanation to dyslexia, in a wide variety of spoken languages and writing
      systems.

PMID- 25590916
TI  - Ultrasound applicability in Speech Language Pathology and Audiology.
AB  - PURPOSE: To present recent studies that used the ultrasound in the fields of
      Speech Language Pathology and Audiology, which evidence possibilities of the
      applicability of this technique in different subareas. RESEARCH STRATEGY: A
      bibliographic research was carried out in the PubMed database, using the keywords
      "ultrasonic," "speech," "phonetics," "Speech, Language and Hearing Sciences,"
      "voice," "deglutition," and "myofunctional therapy," comprising some areas of
      Speech Language Pathology and Audiology Sciences. The keywords "ultrasound,"
      "ultrasonography," "swallow," "orofacial myofunctional therapy," and "orofacial
      myology" were also used in the search. SELECTION CRITERIA: Studies in humans from
      the past 5 years were selected. In the preselection, duplicated studies, articles
      not fully available, and those that did not present direct relation between
      ultrasound and Speech Language Pathology and Audiology Sciences were discarded.
      DATA ANALYSIS: The data were analyzed descriptively and classified subareas of
      Speech Language Pathology and Audiology Sciences. The following items were
      considered: purposes, participants, procedures, and results. RESULTS: We selected
      12 articles for ultrasound versus speech/phonetics subarea, 5 for ultrasound
      versus voice, 1 for ultrasound versus muscles of mastication, and 10 for
      ultrasound versus swallow. Studies relating "ultrasound" and "Speech Language
      Pathology and Audiology Sciences" in the past 5 years were not found. CONCLUSION:
      Different studies on the use of ultrasound in Speech Language Pathology and
      Audiology Sciences were found. Each of them, according to its purpose, confirms
      new possibilities of the use of this instrument in the several subareas, aiming
      at a more accurate diagnosis and new evaluative and therapeutic possibilities.

PMID- 25590917
TI  - Vocal self-assessment: relation with the type of instrument, gender, age, and
      profession in individuals without vocal complaints.
AB  - OBJECTIVE: To obtain the vocal self-assessment rates of individuals without vocal
      complaints and relate them to gender, occupation, and age range. METHODS: This is
      an observational, analytical, and cross-sectional study. In this study, 601
      individuals without vocal complaints, 241 men and 360 women, aged between 18 and
      59 years (mean of 30.1 years) were included. The individuals were divided into
      following age groups: 18-29 years (n=353; 58.7%), 30-44 years (n=159; 26.5%), and
      45-59 years (n=89; 14.8%); 136 individuals (22.6%) were voice professionals and
      465 (77.4%) were nonprofessionals. The individuals answered a questionnaire with
      identification data and the protocols Voice-Related Quality of Life (V-RQOL),
      Voice Handicap Index (VHI), and Voice Activity and Participation Profile (VAPP).
      The data were statistically analyzed. RESULTS: Mean scores obtained in the V
      RQOL, VHI, and VAPP were 95.5, 5.37, and 3.06, respectively. If we transfer these
      values to the base 100, differences were found in the scores of the VHI and VAPP.
      Women presented significantly lower scores in the V-RQOL and VHI. Moreover, there
      were no differences in the mean scores obtained by the different age groups.
      Regarding professional vocal use, there were differences in the VHI and VAPP, and
      the "nonprofessionals" presented lower VHI than professionals. CONCLUSION: The
      type of the instrument, gender, and profession variables can influence the vocal
      self-assessment results.

PMID- 25590918
TI  - Cross-cultural adaptation of the Brazilian version of the protocol Evaluation of
      the Ability to Sing Easily.
AB  - PURPOSE: To present the cross-cultural equivalence of the Brazilian version of
      the Evaluation of the Ability to Sing Easily (EASE) protocol, through its
      cultural and linguistic adaptation. METHODS: After the EASE was translated to
      Brazilian Portuguese, the back-translation into English was done. The items of
      the translated version were compared with the original instrument and the
      discrepancies were modified by consensus of a committee composed of five speech
      language pathologists. The Evaluation of the Ability to Sing Easily for Brazil
      (EASE-BR) has 22 questions with four alternatives: "no," "mildly," "moderately,"
      and "extremely." The score is obtained by the simple sum of all answers. The
      three positive items (6, 12, and 21) require reverse score. For cultural
      equivalence, the EASE-BR was applied with 41 Brazilian singers, with an extra
      item in the answer key - "not applicable." The aim of this extra key was to
      identify issues that might not have been understood or were not appropriate for
      the target population and the Brazilian culture. RESULTS: Of the 32 singers, 5
      who were initially evaluated had difficulties to answer 3 of the 22 questions.
      Therefore, the adaptation of those sentences was necessary. Afterward, the
      modified EASE-BR was applied to nine singers, and no more cultural and/or
      conceptual barriers were found. CONCLUSION: Cultural equivalence was observed
      between EASE and its translated version to the Brazilian Portuguese, the EASE-BR.
      Validation of the EASE for Brazilian Portuguese is in progress.

PMID- 25590919
TI  - Surface layering properties of Intralipid phantoms.
AB  - Intralipid has become an extensively studied and widely used reference and
      calibration phantom for diffuse optical imaging technologies. In this study we
      call attention to the layering properties of Intralipid emulsions, which are
      commonly assumed to have homogeneous optical properties. By measurement of
      spatial frequency domain reflectance in combination with an analytical solution
      of the radiative transfer equation for two-layered media, we make quantitative
      investigations on the formation of a surface layer on different dilutions of
      Intralipid. Our findings are verified by an independent spatially resolved
      reflectance setup giving evidence of a time dependent, thin and highly scattering
      surface layer on top of Intralipid-water emulsions. This layer should be
      considered when using Intralipid as an optical calibration or reference phantom.

PMID- 25590920
TI  - More screen operation than calling: the results of observing cyclists' behaviour
      while using mobile phones.
AB  - Operating a mobile telephone while riding a bicycle is fairly common practice in
      the Netherlands, yet it is unknown if this use is stable or increasing. As such,
      whether the prevalence of mobile phone use while cycling has changed over the
      past five years was studied via on-road observation. In addition the impact of
      mobile phone use on lateral position, i.e. distance from the front wheel to the
      curb, was also examined to see if it compared to the results seen in previous
      experimental studies. Bicyclists were observed at six different locations and
      their behaviour was scored. It was found that compared to five years ago the use
      of mobile phones while cycling has changed, not in frequency, but in how cyclists
      were operating their phones. As found in 2008, three percent of the bicyclists
      were observed to be operating a phone, but a shift from calling (0.7% of cyclists
      observed) to operating (typing, texting, 2.3% of cyclists) was found. In 2008
      nearly the complete opposite usage was observed: 2.2% of the cyclists were
      calling and 0.6% was texting. Another finding was that effects on lateral
      position were similar to those seen in experimental studies in that cyclists
      using a phone maintained a cycling position which was further away from the curb.
      It was also found that when at an intersection, cyclist's operating their phone
      made less head movements to the right than cyclists who were just cycling. This
      shift from calling to screen operation, when combined with the finding related to
      reduced head movements at intersections, is worrying and potentially dangerous. 

PMID- 25590921
TI  - Young driver licensing: examination of population-level rates using New Jersey's
      state licensing database.
AB  - Recent surveys have provided insight on the primary reasons why US teens delay
      licensure but are limited in their ability to estimate licensing rates and
      trends. State administrative licensing data are the ideal source to provide this
      information but have not yet been analyzed for this purpose. Our objective was to
      analyze New Jersey's (NJ) licensing database to: (1) describe population-based
      rates of licensure among 17- to 20-year-olds, overall and by gender and zip code
      level indicators of household income, population density, and race/ethnicity; and
      (2) examine recent trends in licensure. We obtained records on all licensed NJ
      drivers through June 2012 from the NJ Motor Vehicle Commission's licensing
      database and determined each young driver's age at the time of intermediate and
      full licensure. Data from the US Census and American Community Survey were used
      to estimate a fixed cohort of NJ residents who turned 17 years old in 2006-2007
      (n=255,833). Licensing data were used to estimate the number of these drivers who
      obtained an intermediate license by each month of age (numerators) and, among
      those who obtained an intermediate license, time to graduation to full licensure.
      Overall, 40% of NJ residents-and half of those who ultimately obtained a license
      by age 21-were licensed within a month of NJ's minimum licensing age of 17, 64%
      by their 18th birthday, and 81% by their 21st birthday. Starkly different
      patterns of licensure were observed by socioeconomic indicators; for example, 65%
      of 17-year-olds residing in the highest-income zip codes were licensed in the
      first month of eligibility compared with 13% of residents living in the lowest
      income zip codes. The younger an individual obtained their intermediate license,
      the earlier they graduated to a full license. Finally, the rate and timing of
      licensure in NJ has been relatively stable from 2006 to 2012, with at most a 1-3%
      point decline in rates. These findings support the growing body of literature
      suggesting that teens delay licensure primarily for economic reasons and that a
      substantial proportion of potentially high-risk teens may be obtaining licenses
      outside the auspices of a graduated driver licensing system. Finally, our finding
      of a relatively stable trend in licensure in recent years is in contrast to
      national-level reports of a substantial decline in licensure rates. 

PMID- 25590922
TI  - Atrial septal defect in adults: does repair always mean cure?

PMID- 25590923
TI  - Effectiveness of biomarkers in cardiology.

PMID- 25590925
TI  - Value of the Qrs-T angle in predicting the induction of ventricular
      tachyarrhythmias in patients with Chagas disease.
AB  - BACKGROUND: The QRS-T angle correlates with prognosis in patients with heart
      failure and coronary artery disease, reflected by an increase in mortality
      proportional to an increase in the difference between the axes of the QRS complex
      and T wave in the frontal plane. The value of this correlation in patients with
      Chagas heart disease is currently unknown. OBJECTIVE: Determine the correlation
      of the QRS-T angle and the risk of induction of ventricular tachycardia /
      ventricular fibrillation (VT / VF) during electrophysiological study (EPS) in
      patients with Chagas disease. METHODS: Case-control study at a tertiary center.
      Patients without induction of VT / VF on EPS were used as controls. The QRS-T
      angle was categorized as normal (0-105o), borderline (105-135o) or abnormal (135
      180o). Differences between groups for continuous variables were analyzed with the
      t test or Mann-Whitney test, and for categorical variables with Fisher's exact
      test. P values < 0.05 were considered significant. RESULTS: Of 116 patients
      undergoing EPS, 37.9% were excluded due to incomplete information / inactive
      records or due to the impossibility to correctly calculate the QRS-T angle
      (presence of left bundle branch block and atrial fibrillation). Of 72 patients
      included in the study, 31 induced VT / VF on EPS. Of these, the QRS-T angle was
      normal in 41.9%, borderline in 12.9% and abnormal in 45.2%. Among patients
      without induction of VT / VF on EPS, the QRS-T angle was normal in 63.4%,
      borderline in 14.6% and abnormal in 17.1% (p = 0.04). When compared with patients
      with normal QRS-T angle, those with abnormal angle had a fourfold higher risk of
      inducing ventricular tachycardia / ventricular fibrillation on EPS [odds ratio
      (OR) 4; confidence interval (CI) 1.298-12.325; p = 0.028]. After adjustment for
      other variables such as age, ejection fraction (EF) and QRS size, there was a
      trend for the abnormal QRS-T angle to identify patients with increased risk of
      inducing VT / VF during EPS (OR 3.95; CI 0.99-15.82; p = 0.052). The EF also
      emerged as a predictor of induction of VT / VF: for each point increase in EF,
      there was a 4% reduction in the rate of sustained ventricular arrhythmia on EPS.
      CONCLUSIONS: Changes in the QRS-T angle and decreases in EF were associated with
      an increased risk of induction of VT / VF on EPS.

PMID- 25590924
TI  - Biomarkers in cardiology--part 1--in heart failure and specific cardiomyopathies.
AB  - Cardiovascular diseases are the leading causes of mortality and morbidity in
      Brazil. The primary and secondary preventions of those diseases are a priority
      for the health system and require multiple approaches to increase their
      effectiveness. Biomarkers are tools used to more accurately identify high-risk
      individuals, to speed the diagnosis, and to aid in treatment and prognosis
      determination. This review aims to highlight the importance of biomarkers in
      clinical cardiology practice, and to raise relevant points of their use and the
      promises for the coming years. This document was divided into two parts, and this
      first one discusses the use of biomarkers in specific cardiomyopathies and heart
      failure. 

PMID- 25590926
TI  - Late outcome of a randomized study on oral magnesium for premature complexes.
AB  - BACKGROUND: Ventricular and supraventricular premature complexes (PC) are
      frequent and usually symptomatic. According to a previous study, magnesium
      pidolate (MgP) administration to symptomatic patients can improve the PC density
      and symptoms. OBJECTIVE: To assess the late follow-up of that clinical
      intervention in patients treated with MgP or placebo. METHODS: In the first phase
      of the study, 90 symptomatic and consecutive patients with PC were randomized
      (double-blind) to receive either MgP or placebo for 30 days. Monthly follow-up
      visits were conducted for 15 months to assess symptoms and control electrolytes.
      24-hour Holter was performed twice, regardless of symptoms, or whenever symptoms
      were present. In the second phase of the study, relapsing patients, who had
      received MgP or placebo (crossing-over) in the first phase, were treated with MgP
      according to the same protocol. RESULTS: Of the 45 patients initially treated
      with MgP, 17 (37.8%) relapsed during the 15-month follow-up, and the relapse time
      varied. Relapsing patients treated again had a statistically significant
      reduction in the PC density of 138.25/hour (p < 0.001). The crossing-over
      patients reduced it by 247/hour (p < 0.001). Patients who did not relapse, had a
      low PC frequency (3 PC/hour). Retreated patients had a 76.5% improvement in
      symptom, and crossing-over patients, 71.4%. CONCLUSION: Some patients on MgP had
      relapse of symptoms and PC, indicating that MgP is neither a definitive nor a
      curative treatment for late follow-up. However, improvement in the PC frequency
      and symptoms was observed in the second phase of treatment, similar to the
      response in the first phase of treatment.

PMID- 25590927
TI  - Prevalence of dyslipidemia according to the nutritional status in a
      representative sample of Sao Paulo.
AB  - BACKGROUND: Overweight is one of the major public health problems in Brazil; it
      is associated with dyslipidemia, which is an important risk factor for
      cardiovascular diseases. OBJECTIVE: To evaluate the lipid profile of residents of
      the municipality of Sao Paulo, state of Sao Paulo, according to the nutritional
      status. METHODS: Data from the population-based cross-sectional study ISA-Capital
      2008 on a sample of residents of Sao Paulo were used. Participants were
      categorized into groups according to body mass index and age range. The levels of
      total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and non-HDL
      cholesterol were measured. The association between lipid profile, nutricional
      status, and waist circumference was investigated. The data were processed using
      the survey mode of the Stata 11.0 software. RESULTS: The prevalence of any type
      of dyslipidemia in the population was 59.74%, with low HDL-cholesterol
      dyslipidemia being the most common type. Not overweight individuals had higher
      mean levels of HDL-cholesterol and lower levels of LDL-cholesterol, total
      cholesterol, triglycerides, and non-HDL cholesterol when compared with the
      overweight group. The rate of inadequacy of these variables was higher in the
      overweight individuals, regardless of the age group, to the exception of LDL
      cholesterol in the adults and elderly. A higher prevalence of isolated
      hypertriglyceridemia was observed in individuals with higher waist circumference
      among the adults and the total population. CONCLUSION: The results indicate an
      association between dyslipidemia and overweight in the population of the city of
      Sao Paulo. The most prevalent dyslipidemia in this population was low HDL
      cholesterol.

PMID- 25590928
TI  - Impact of atrial fibrillation ablation on left ventricular filling pressure and
      left atrial remodeling.
AB  - BACKGROUND: Left ventricular (LV) diastolic dysfunction is associated with new
      onset atrial fibrillation (AF), and the estimation of elevated LV filling
      pressures by E/e' ratio is related to worse outcomes in patients with AF.
      However, it is unknown if restoring sinus rhythm reverses this process.
      OBJECTIVE: To evaluate the impact of AF ablation on estimated LV filling
      pressure. METHODS: A total of 141 patients underwent radiofrequency (RF) ablation
      to treat drug-refractory AF. Transthoracic echocardiography was performed 30 days
      before and 12 months after ablation. LV functional parameters, left atrial volume
      index (LAVind), and transmitral pulsed and mitral annulus tissue Doppler (e' and
      E/e') were assessed. Paroxysmal AF was present in 18 patients, persistent AF was
      present in 102 patients, and long-standing persistent AF in 21 patients. Follow
      up included electrocardiographic examination and 24-h Holter monitoring at 3, 6,
      and 12 months after ablation. RESULTS: One hundred seventeen patients (82.9%)
      were free of AF during the follow-up (average, 18 +/- 5 months). LAVind reduced
      in the successful group (30.2 mL/m(2) +/- 10.6 mL/m(2) to 22.6 mL/m(2) +/- 1.1
      mL/m(2), p < 0.001) compared to the non-successful group (37.7 mL/m(2) +/- 14.3
      mL/m(2) to 37.5 mL/m(2) +/- 14.5 mL/m(2), p = ns). Improvement of LV filling
      pressure assessed by a reduction in the E/e' ratio was observed only after
      successful ablation (11.5 +/- 4.5 vs. 7.1 +/- 3.7, p < 0.001) but not in patients
      with recurrent AF (12.7 +/- 4.4 vs. 12 +/- 3.3, p = ns). The success rate was
      lower in the long-standing persistent AF patient group (57% vs. 87%, p = 0.001).
      CONCLUSION: Successful AF ablation is associated with LA reverse remodeling and
      an improvement in LV filling pressure.

PMID- 25590929
TI  - Comparison of cardiovascular risk factors in different areas of health care over
      a 20-year period.
AB  - BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death
      worldwide. Knowledge about cardiovascular risk factors (CVRFs) in young adults
      and their modification over time are measures that change the risks and prevent
      CVDs. OBJECTIVES: To determine the presence of CVRFs and their changes in
      different health care professionals over a period of 20 years. METHODS: All
      students of medicine, nursing, nutrition, odontology, and pharmacy departments of
      Federal University of Goias who agreed to participate in this study were
      evaluated when they started their degree courses and 20 years afterward.
      Questionnaires on CVRFs [systemic arterial hypertension (SAH), diabetes mellitus,
      dyslipidemia, and family history of early CVD, smoking, alcohol consumption, and
      sedentarism] were administered. Cholesterol levels, blood sugar levels, blood
      pressure, weight, height, and body mass index were determined. The Kolmogorov
      Smirnov test was used to evaluate distribution, the chi-square test was used to
      compare different courses and sexes, and the McNemar test was used for comparing
      CVRFs. The significance level was set at a p value of < 0.05. RESULTS: The first
      stage of the study included 281 individuals (91% of all the students), of which
      62.9% were women; the mean age was 19.7 years. In the second stage, 215 subjects
      were reassessed (76% of the initial sample), of which 59.07% were women; the mean
      age was 39.8 years. The sample mostly consisted of medical students (with a
      predominance of men), followed by nursing, nutrition, and pharmacy students, with
      a predominance of women (p < 0.05). Excessive weight gain, SAH, and dyslipidemia
      were observed among physicians and dentists (p < 0.05). Excessive weight gain and
      SAH and a reduction in sedentarism (p < 0.05) were observed among pharmacists.
      Among nurses there was an increase in excessive weight and alcohol consumption (p
      < 0.05). Finally, nutritionists showed an increase in dyslipidemia (p < 0.05).
      CONCLUSION: In general, there was an unfavorable progression of CVRFs in the
      population under study, despite it having adequate specialized knowledge about
      these risk factors.

PMID- 25590930
TI  - Improving post-discharge medication adherence in patients with CVD: a pilot
      randomized trial.
AB  - BACKGROUND: Effective interventions to improve medication adherence are usually
      complex and expensive. OBJECTIVE: To assess the impact of a low-cost intervention
      designed to improve medication adherence and clinical outcomes in post-discharge
      patients with CVD. METHOD: A pilot RCT was conducted at a teaching hospital.
      Intervention was based on the four-item Morisky Medication Adherence Scale (MMAS
      4). The primary outcome measure was medication adherence assessed using the eight
      item MMAS at baseline, at 1 month post hospital discharge and re-assessed 1 year
      after hospital discharge. Other outcomes included readmission and mortality
      rates. RESULTS: 61 patients were randomized to intervention (n = 30) and control
      (n = 31) groups. The mean age of the patients was 61 years (SD 12.73), 52.5% were
      males, and 57.4% were married or living with a partner. Mean number of prescribed
      medications per patient was 4.5 (SD 3.3). Medication adherence was correlated to
      intervention (p = 0.04) and after 1 month, 48.4% of patients in the control group
      and 83.3% in the intervention group were considered adherent. However, this
      difference decreased after 1 year, when adherence was 34.8% and 60.9%,
      respectively. Readmission and mortality rates were related to low adherence in
      both groups. CONCLUSION: The intervention based on a validated patient self
      report instrument for assessing adherence is a potentially effective method to
      improve adherent behavior and can be successfully used as a tool to guide
      adherence counseling in the clinical visit. However, a larger study is required
      to assess the real impact of intervention on these outcomes.

PMID- 25590931
TI  - Association between angiotensin-converting enzyme inhibitors and troponin in
      acute coronary syndrome.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of mortality in the
      western world and its treatment should be optimized to decrease severe adverse
      events. OBJECTIVE: To determine the effect of previous use of angiotensin
      converting enzyme inhibitors on cardiac troponin I measurement in patients with
      acute coronary syndrome without ST-segment elevation and evaluate clinical
      outcomes at 180 days. METHODS: Prospective, observational study, carried out in a
      tertiary center, in patients with acute coronary syndrome without ST-segment
      elevation. Clinical, electrocardiographic and laboratory variables were analyzed,
      with emphasis on previous use of angiotensin-converting enzyme inhibitors and
      cardiac troponin I. The Pearson chi-square tests (Pereira) or Fisher's exact test
      (Armitage) were used, as well as the non-parametric Mann-Whitney's test.
      Variables with significance levels of <10% were submitted to multiple logistic
      regression model. RESULTS: A total of 457 patients with a mean age of 62.1 years,
      of whom 63.7% were males, were included. Risk factors such as hypertension
      (85.3%) and dyslipidemia (75.9%) were the most prevalent, with 35% of diabetics.
      In the evaluation of events at 180 days, there were 28 deaths (6.2%). The
      statistical analysis showed that the variables that interfered with troponin
      elevation (> 0.5 ng / mL) were high blood glucose at admission (p = 0.0034) and
      ST-segment depression >= 0.5 mm in one or more leads (p = 0.0016). The use of
      angiotensin-converting inhibitors prior to hospitalization was associated with
      troponin <= 0.5 ng / mL (p = 0.0482). The C-statistics for this model was 0.77.
      CONCLUSION: This study showed a correlation between prior use of angiotensin
      converting enzyme inhibitors and reduction in the myocardial necrosis marker
      troponin I in patients admitted for acute coronary syndrome without ST-segment
      elevation. However, there are no data available yet to state that this reduction
      could lead to fewer severe clinical events such as death and re-infarction at 180
      days.

PMID- 25590932
TI  - Autologous transplantation of bone marrow adult stem cells for the treatment of
      idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Morbimortality in patients with dilated idiopathic cardiomyopathy is
      high, even under optimal medical treatment. Autologous infusion of bone marrow
      adult stem cells has shown promising preliminary results in these patients.
      OBJECTIVE: Determine the effectiveness of autologous transplantation of bone
      marrow adult stem cells on systolic and diastolic left ventricular function, and
      on the degree of mitral regurgitation in patients with dilated idiopathic
      cardiomyopathy in functional classes NYHA II and III. METHODS: We administered
      4,54 x 10(8) +/- 0,89 x 10(8) bone marrow adult stem cells into the coronary
      arteries of 24 patients with dilated idiopathic cardiomyopathy in functional
      classes NYHA II and III. Changes in functional class, systolic and diastolic left
      ventricular function and degree of mitral regurgitation were assessed after 3
      months, 6 months and 1 year. RESULTS: During follow-up, six patients (25%)
      improved functional class and eight (33.3%) kept stable. Left ventricular
      ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p =
      0.024; 0.017 and 0.018), respectively. There were no significant changes neither
      in diastolic left ventricular function nor in mitral regurgitation degree. A
      combined cardiac resynchronization and implantable cardioversion defibrillation
      was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and
      four patients died due to terminal cardiac failure. Average survival of these
      eight patients was 2.6 years. CONCLUSION: Intracoronary infusion of bone marrow
      adult stem cells was associated with an improvement or stabilization of
      functional class and an improvement in left ventricular ejection fraction,
      suggesting the efficacy of this intervention. There were no significant changes
      neither in left ventricular diastolic function nor in the degree of mitral
      regurgitation.

PMID- 25590936
TI  - Case 6/2014--A case of a 61-year-old woman with diastolic heart failure.

PMID- 25590933
TI  - Focused cardiac ultrasound using a pocket-size device in the emergency room.
AB  - BACKGROUND: Cardiovascular urgencies are frequent reasons for seeking medical
      care. Prompt and accurate medical diagnosis is critical to reduce the morbidity
      and mortality of these conditions. OBJECTIVE: To evaluate the use of a pocket
      size echocardiography in addition to clinical history and physical exam in a
      tertiary medical emergency care. METHODS: One hundred adult patients without
      known cardiac or lung diseases who sought emergency care with cardiac complaints
      were included. Patients with ischemic changes in the electrocardiography or fever
      were excluded. A focused echocardiography with GE Vscan equipment was performed
      after the initial evaluation in the emergency room. Cardiac chambers dimensions,
      left and right ventricular systolic function, intracardiac flows with color,
      pericardium, and aorta were evaluated. RESULTS: The mean age was 61 +/- 17 years
      old. The patient complaint was chest pain in 51 patients, dyspnea in 32 patients,
      arrhythmia to evaluate the left ventricular function in ten patients,
      hypotension/dizziness in five patients and edema in one patient. In 28 patients,
      the focused echocardiography allowed to confirm the initial diagnosis: 19
      patients with heart failure, five with acute coronary syndrome, two with
      pulmonary embolism and two patients with cardiac tamponade. In 17 patients, the
      echocardiography changed the diagnosis: ten with suspicious of heart failure, two
      with pulmonary embolism suspicious, two with hypotension without cause, one
      suspicious of acute coronary syndrome, one of cardiac tamponade and one of aortic
      dissection. CONCLUSION: The focused echocardiography with pocket-size equipment
      in the emergency care may allow a prompt diagnosis and, consequently, an earlier
      initiation of the therapy.

PMID- 25590934
TI  - Development of anatomophysiologic knowledge regarding the cardiovascular system:
      from Egyptians to Harvey.
AB  - Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS)
      has progressed since the fourth millennium BC. In Egypt (3500 BC), it was
      believed that a set of channels are interconnected to the heart, transporting
      air, urine, air, blood, and the soul. One thousand years later, the heart was
      established as the center of the CVS by the Hippocratic Corpus in the medical
      school of Kos, and some of the CVS anatomical characteristics were defined. The
      CVS was known to transport blood via the right ventricle through veins and the
      pneuma via the left ventricle through arteries. Two hundred years later, in
      Alexandria, following the development of human anatomical dissection, Herophilus
      discovered that arteries were 6 times thicker than veins, and Erasistratus
      described the semilunar valves, emphasizing that arteries were filled with blood
      when ventricles were empty. Further, 200 years later, Galen demonstrated that
      arteries contained blood and not air. With the decline of the Roman Empire, Greco
      Roman medical knowledge about the CVS was preserved in Persia, and later in Islam
      where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of
      dissection of the human body in Europe in the 14th century was associated with
      the revival of the knowledge pertaining to the CVS. The main findings were the
      description of pulmonary circulation by Servetus, the anatomical discoveries of
      Vesalius, the demonstration of pulmonary circulation by Colombo, and the
      discovery of valves in veins by Fabricius. Following these developments, Harvey
      described blood circulation. 

PMID- 25590937
TI  - Severe coronary vasospasm complicated with ventricular tachycardia.

PMID- 25590938
TI  - Cardiac tamponade caused by compression of right cardiac chamber: a hidden enemy.

PMID- 25590939
TI  - Effectiveness of a fotonovela for reducing depression and stress in Latino
      dementia family caregivers.
AB  - The clinical need to address stress and depression in Latino dementia caregivers
      (CGs) combined with low health literacy and less accurate knowledge of dementia
      motivated the development of a pictorial tool [called a fotonovela (FN)] to teach
      (a) coping skills for caregiver (CG) stress; (b) self-assessment of depression;
      and (c) encourage improved utilization of available resources. To test the
      effectiveness of the FN, 110 of 147 Latino CGs, who were randomly assigned to the
      Fotonovela Condition (FNC) or the Usual Information Condition (UIC), were
      included in the final analyses. Self-report measures were given at baseline and
      post intervention. Results showed that FNC CGs demonstrated significantly greater
      reductions in level of depressive symptoms than UIC CGs. A significant decrease
      in level of stress due to memory and behavioral problems exhibited by their loved
      ones was similar in both groups. The FNC CGs reported that the FN was more
      helpful and that they referred to it more often than the UIC CGs did with regard
      to the informational materials they were provided about dementia. In conclusion,
      a culturally tailored FN can be an effective tool for Latino CGs given their high
      unmet needs for assistance and various barriers in accessing resources. 

PMID- 25590940
TI  - Deficits in Everyday Function Differ in AD and FTD.
AB  - Alzheimer disease (AD) and frontotemporal dementia (FTD) are 2 neurodegenerative
      diseases with differing cognitive and neuropathologic profiles. Although both
      diseases ultimately result in functional disability, differences in the profiles
      of everyday functioning between the 2 groups have not been well characterized.
      The present study examines potential differences in the types of everyday
      functional limitations present in these 2 dementias. The present study compared
      individuals with AD (N=240) or FTD (N=13). The Everyday Cognition (ECog) scale
      was used to measure distinct domains of everyday cognition: everyday memory,
      everyday language, everyday visuospatial ability, and a variety of everyday
      executive abilities. A total ECog score was used to represent global disability
      level. The groups showed equivalent levels of global disability. However, AD
      group exhibited worse Everyday Memory and Everyday Visuospatial abilities than
      the FTD group. Contrary to expectation, FTD was not more impaired in everyday
      executive abilities. Results remained similar when accounting for severity of
      cognitive impairment or disease duration. Findings suggest that a somewhat
      different pattern of everyday functional difficulties can be seen across dementia
      types. 

PMID- 25590941
TI  - Study on the pharmacokinetics profiles of polyphyllin I and its bioavailability
      enhancement through co-administration with P-glycoprotein inhibitors by LC-MS/MS
      method.
AB  - Polyphyllin I (PPI), one of the steroidal saponins in Paris polyphylla, is a
      promising natural anticancer candidate. Although the anticancer activity of PPI
      has been well demonstrated, information regarding the pharmacokinetics and
      bioavailability is limited. In this study, a series of reliable and rapid liquid
      chromatography-tandem mass spectrometry methods were developed and successfully
      applied to determinate PPI in rat plasma, cell incubation media and cell
      homogenate. Then the pharmacokinetics of PPI in rats was studied and the result
      revealed that PPI was slowly eliminated with low oral bioavailability (about
      0.62%) at a dose of 50 mg/kg, and when co-administrated with verapamil (VPL) and
      cyclosporine A (CYA), the oral bioavailability of PPI could increase from 0.62%
      to 3.52% and 3.79% respectively. In addition, in vitro studies showed that with
      the presence of VPL and CYA in Caco-2 cells, the efflux ratio of PPI decreased
      from 12.5 to 2.96 and 2.22, and the intracellular concentrations increased 5.8-
      and 5.0-fold respectively. These results demonstrated that PPI, with poor oral
      bioavailability, is greatly impeded by P-gp efflux, and inhibition of P-gp can
      enhance its bioavailability.

PMID- 25590942
TI  - Multi-responses extraction optimization combined with high-performance liquid
      chromatography-diode array detection-electrospray ionization-tandem mass
      spectrometry and chemometrics techniques for the fingerprint analysis of Aloe
      barbadensis Miller.
AB  - A quality control strategy using high-performance liquid chromatography-diode
      array detector-electrospray ionization-tandem mass spectrometry (HPLC-DAD-ESI
      MS/MS) coupled with chemometrics analysis was proposed for Aloe barbadensis
      Miller. Firstly, the extraction conditions including methanol concentration,
      extraction time and solvent-to-material ratio were optimized by multi-responses
      optimization based on response surface methodology (RSM). The optimum conditions
      were achieved by Derringer's desirability function and experimental validation
      implied that the established model exhibited favorable prediction ability. Then,
      HPLC fingerprint consisting of 27 common peaks was developed among 15 batches of
      A. barbadensis samples. 25 common peaks were identified using HPLC-DAD-ESI-MS/MS
      method by their spectral characteristics or comparison with the authentic
      standards. Chemometrics techniques including similarity analysis (SA), principal
      components analysis (PCA) and hierarchical clustering analysis (HCA) were
      implemented to classify A. barbadensis samples. The results demonstrated that all
      A. barbadensis samples shared similar chromatographic patterns as well as
      differences. These achievements provided an effective, reliable and comprehensive
      quality control method for A. barbadensis. 

PMID- 25590943
TI  - Profiling and multivariate statistical analysis of Panax ginseng based on ultra
      high-performance liquid chromatography coupled with quadrupole-time-of-flight
      mass spectrometry.
AB  - An ultra-high-performance liquid chromatography coupled with quadrupole-time-of
      flight mass spectrometry (UHPLC-Q-TOF-MS) method was developed for the detection
      and structural analysis of ginsenosides in white ginseng and related processed
      products (red ginseng). Original neutral, malonyl, and chemically transformed
      ginsenosides were identified in white and red ginseng samples. The aglycone types
      of ginsenosides were determined by MS/MS as PPD (m/z 459), PPT (m/z 475), C-24, 
      25 hydrated-PPD or PPT (m/z 477 or m/z 493), and Delta20(21)-or Delta20(22)
      dehydrated-PPD or PPT (m/z 441 or m/z 457). Following the structural
      determination, the UHPLC-Q-TOF-MS-based chemical profiling coupled with
      multivariate statistical analysis method was applied for global analysis of white
      and processed ginseng samples. The chemical markers present between the processed
      products red ginseng and white ginseng could be assigned. Process-mediated
      chemical changes were recognized as the hydrolysis of ginsenosides with large
      molecular weight, chemical transformations of ginsenosides, changes in malonyl
      ginsenosides, and generation of 20-(R)-ginsenoside enantiomers. The relative
      contents of compounds classified as PPD, PPT, malonyl, and transformed
      ginsenosides were calculated based on peak areas in ginseng before and after
      processing. This study provides possibility to monitor multiple components for
      the quality control and global evaluation of ginseng products during processing. 

PMID- 25590944
TI  - The effect of excipients on the stability and phase transition rate of xylazine
      hydrochloride and zopiclone.
AB  - The compatibility of thermodynamically unstable polymorph of two active
      pharmaceutical compounds (xylazine hydrochloride form X and zopiclone form C)
      with different excipients was investigated. The effects of the excipient and its
      amount in the sample on the thermal properties and possible chemical interactions
      were studied. The most commonly used excipients in the pharmaceutical industry -
      calcium carbonate, lactose hydrate, cellulose, magnesium stearate hydrate and
      calcium stearate hydrate were selected for this study. The dependence of the
      phase transition rate from an unstable to a more stable polymorph on the
      excipients and their amounts in the initial sample was analysed at 80 degrees C,
      and the corresponding phase transition rate constants were calculated. 

PMID- 25590945
TI  - Prediction of hydrolysis pathways and kinetics for antibiotics under
      environmental pH conditions: a quantum chemical study on cephradine.
AB  - Understanding hydrolysis pathways and kinetics of many antibiotics that have
      multiple hydrolyzable functional groups is important for their fate assessment.
      However, experimental determination of hydrolysis encounters difficulties due to
      time and cost restraint. We employed the density functional theory and transition
      state theory to predict the hydrolysis pathways and kinetics of cephradine, a
      model of cephalosporin with two hydrolyzable groups, two ionization states, two
      isomers and two nucleophilic attack directions. Results showed that the
      hydrolysis of cephradine at pH = 8.0 proceeds via opening of the beta-lactam ring
      followed by intramolecular amidation. The predicted rate constants at different
      pH conditions are of the same order of magnitude as the experimental values, and
      the predicted products are confirmed by experiment. This study identified a
      catalytic role of the carboxyl group in the hydrolysis, and implies that the
      carboxyl group also plays a catalytic role in the hydrolysis of other
      cephalosporin and penicillin antibiotics. This is a first attempt to quantum
      chemically predict hydrolysis of an antibiotic with complex pathways, and
      indicates that to predict hydrolysis products under the environmental pH
      conditions, the variation of the rate constants for different pathways with pH
      should be evaluated. 

PMID- 25590946
TI  - Probability in reasoning: a developmental test on conditionals.
AB  - Probabilistic theories have been claimed to constitute a new paradigm for the
      psychology of reasoning. A key assumption of these theories is captured by what
      they call the Equation, the hypothesis that the meaning of the conditional is
      probabilistic in nature and that the probability of If p then q is the
      conditional probability, in such a way that P(if p then q)=P(q|p). Using the
      probabilistic truth-table task in which participants are required to evaluate the
      probability of If p then q sentences, the present study explored the
      pervasiveness of the Equation through ages (from early adolescence to adulthood),
      types of conditionals (basic, causal, and inducements) and contents. The results
      reveal that the Equation is a late developmental achievement only endorsed by a
      narrow majority of educated adults for certain types of conditionals depending on
      the content they involve. Age-related changes in evaluating the probability of
      all the conditionals studied closely mirror the development of truth-value
      judgements observed in previous studies with traditional truth-table tasks. We
      argue that our modified mental model theory can account for this development, and
      hence for the findings related with the probability task, which do not
      consequently support the probabilistic approach of human reasoning over
      alternative theories. 

PMID- 25590947
TI  - Income deprivation and mental well-being: the role of non-cognitive skills.
AB  - We show that the positive relation between income deprivation and mental health
      is affected by an individual's non-cognitive skills. Income deprivation is
      operationalized as the Yitzhaki index, i.e., as a function of the sum of income
      differences between an individual and others in her reference group who are more
      affluent. Non-cognitive skills are extracted from a Locus of Control
      questionnaire and the Big Five Inventory, a self-report measurement of an
      individual in regard to five aspects of personality: conscientiousness,
      neuroticism, extraversion, agreeableness and open-mindedness. The results, based
      on the 2002-2010 waves of the German Socio-Economic Panel dataset (SOEP), show
      that deprivation is negative and significantly related with mental health.
      However, neurotic individuals are more deprivation-sensitive than are others.
      Compared to the mean effect, a one standard deviation rise in neuroticism is
      associated with a deprivation effect that is 36.6% and 51.9% larger among men and
      women, respectively. Although to a lesser extent, extraverted men and
      conscientious women are also found to be more deprivation-sensitive than are
      others, the corresponding figures being 31.1% and 45.9%, respectively. These
      findings suggest that personality differences should be taken into account in the
      design of policies, practices and initiatives aimed at alleviating the well-being
      costs of income deprivation. 

PMID- 25590948
TI  - OCT1 in hepatic steatosis and thiamine disposition.

PMID- 25590949
TI  - Modulation of charge transport across double-stranded DNA by the site-specific
      incorporation of copper bis-phenanthroline complexes.
AB  - The site-specific incorporation of transition-metal complexes within DNA
      duplexes, followed by their immobilization on a gold surface, was studied by
      electrochemistry to characterize their ability to mediate charge. Cyclic
      voltammetry, square-wave voltammetry, and control experiments were carried out on
      fully matched and mismatched DNA strands that are mono- or bis-labeled with
      transition-metal complexes. These experiments are all consistent with the ability
      of the metal centers to act as a redox probe that is well coupled to the DNA pi
      stack, allowing DNA-mediated charge transport. 

PMID- 25590950
TI  - The Glycemic Index of Rice and Rice Products: A Review, and Table of GI Values.
AB  - Rice is the principle staple and energy source for nearly half the world's
      population and therefore has significant nutrition and health implications. Rice
      is generally considered a high glycemic index (GI) food, however, this depends on
      varietal, compositional, processing, and accompaniment factors. Being a major
      contributor to the glycemic load in rice eating populations, there is increasing
      concern that the rising prevalence of insulin resistance is as a result of the
      consumption of large amounts of rice. Devising ways and means of reducing the
      glycemic impact of rice is therefore imperative. This review gathers studies
      examining the GI of rice and rice products and provides a critical overview of
      the current state of the art. A table collating published GI values for rice and
      rice products is also included. 

PMID- 25590952
TI  - Vitamin D deficiency predisposes to adherent-invasive Escherichia coli-induced
      barrier dysfunction and experimental colonic injury.
AB  - BACKGROUND: Adherent-invasive Escherichia coli (AIEC) colonization has been
      strongly implicated in the pathogenesis of Crohn's disease. Environmental
      triggers such as vitamin D deficiency have emerged as key factors in the
      pathogenesis of inflammatory bowel diseases. The aim of this study was to
      investigate the effects of 1,25(OH)2D3 on AIEC infection-induced changes in vivo
      and in vitro. METHODS: Barrier function was assessed in polarized epithelial Caco
      2-bbe cells grown in medium with or without vitamin D and challenged with AIEC
      strain LF82. Weaned C57BL/6 mice were fed either a vitamin D-sufficient or 
      deficient diet for 5 weeks and then infected with AIEC, in the absence and
      presence of low-dose dextran sodium sulphate. Disease severity was assessed by
      histological analysis and in vivo intestinal permeability assay. Presence of
      invasive bacteria was assessed by transmission electron microscopy. RESULTS: Caco
      2-bbe cells incubated with 1,25(OH)2D3 were protected against AIEC-induced
      disruption of transepithelial electrical resistance and tight-junction protein
      redistribution. Vitamin D-deficient C57BL/6 mice given a course of 2% dextran
      sodium sulphate exhibited pronounced epithelial barrier dysfunction, were more
      susceptible to AIEC colonization, and showed exacerbated colonic injury.
      Transmission electron microscopy of colonic tissue from infected mice
      demonstrated invasion of AIEC and fecal microbiome analysis revealed shifts in
      microbial communities. CONCLUSIONS: These data show that vitamin D is able to
      mitigate the deleterious effects of AIEC on the intestinal mucosa, by maintaining
      intestinal epithelial barrier homeostasis and preserving tight-junction
      architecture. This study highlights the association between vitamin D status,
      dysbiosis, and Crohn's disease.

PMID- 25590954
TI  - Size-based microfluidic multimodal microparticle sorter.
AB  - Microfluidic sorting of synthetic and biological microparticles has attracted
      much interest in recent years. Inertial microfluidics uses hydrodynamic forces to
      manipulate migration of such microparticles in microfluidic channels to achieve
      passive sorting based on size with high throughput. However, most inertial
      microfluidic devices are only capable of bimodal separation with a single cutoff
      diameter and a well-defined size difference. These limitations inhibit efficient
      separation of real-world samples that often include heterogeneous mixtures of
      multiple microparticle components. Our design overcomes these challenges to
      achieve continuous multimodal sorting of microparticles with high resolution and
      high tunability of separation cutoff diameters. We demonstrate separations with
      flexible modulation of the separation bandwidth and the passband location. Our
      approach offers a number of benefits, including straightforward system design,
      easily and precisely tuned cutoff diameters, high separation resolution, and high
      throughput. Ultimately, the unique multimodal separation functionality
      significantly broadens applications of inertial microfluidics in sorting of
      complex microparticle samples. 

PMID- 25590955
TI  - Chronic obstructive pulmonary disease in nonsmokers by occupation and exposure: a
      brief review.
AB  - PURPOSE OF REVIEW: This review gives an overview on recent reports of various
      occupations associated with chronic obstructive pulmonary disease (COPD) and
      exposures to associate with COPD among nonsmokers. RECENT FINDINGS: Recent
      research has focused on identifying occupations with increased risk of COPD and
      exposures associated with COPD among nonsmokers based on national health survey
      data in the United States and studies in other countries. Recently reported
      prevalence of COPD among nonsmokers was 2.8% in the United States and the
      prevalence in other countries varied from 2% to 4.2%. The newly identified
      occupations with high COPD prevalence include machine operators, construction
      trades, financial record processing, cotton workers, farm machinery workers,
      construction workers, and bus drivers. SUMMARY: The results of various studies
      among nonsmokers show that some occupations are associated with an increased risk
      of developing COPD, but no exact causes are reported. More research is needed to
      confirm the newly identified occupations associated with an increased risk of
      COPD and to identify causal risk factors. To reduce the prevalence of COPD in the
      workplace, etiologic research and preventive interventions should focus on
      occupations at risk for occupational exposures.

PMID- 25590953
TI  - Biologic concentration testing in inflammatory bowel disease.
AB  - Anti-TNF medications have revolutionized the care of patients with inflammatory
      bowel disease. However, despite an initial robust effect, loss of response is
      common and long-term results are disappointing. Much of this lack of durability
      may be due to inadequate dose optimization, and recent studies suggest a
      correlation between serum drug concentrations and clinical outcomes. Currently,
      in clinical practice, measurement of drug concentrations and antibodies to drug
      are typically performed only when a patient presents with active inflammatory
      bowel disease symptoms or during a potential immune-mediated reaction to anti-TNF
      ("reactive" setting). However, proactive monitoring of anti-TNF concentrations
      with titration to a therapeutic window (i.e., therapeutic concentration
      monitoring) represents a new strategy with many potential clinical benefits
      including prevention of immunogenicity, less need for IFX rescue therapy, and
      greater durability of IFX treatment. This review will cover the salient features
      of anti-TNF pharmacokinetics and pharmacodynamics and provide a rational approach
      for the use of anti-TNF concentration testing in both the reactive and proactive
      settings. 

PMID- 25590956
TI  - Optical coherence tomography evaluation of overlapping everolimus-eluting
      bioresorbable vascular scaffold implantation guided by enhanced stent
      visualization system.

PMID- 25590957
TI  - Risk of myocardial contusion in cardiac arrest patients resuscitated with
      mechanical chest compression device.

PMID- 25590958
TI  - Body size and high intake of salt is associated with elevated blood pressure
      among children and adolescents in Shandong, China.

PMID- 25590959
TI  - Cardioprotection with melatonin in the acute myocardial infarction: awaiting
      results of MARIA trial?

PMID- 25590960
TI  - Thrombosis in Fontan patient on apixaban.

PMID- 25590962
TI  - Mechanism of PKC activity affecting the adhesion reaction of endothelial cells
      with monocytes.

PMID- 25590961
TI  - Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a
      reservoir of anti-apoptotic microRNAs for cardioprotection.
AB  - BACKGROUND: Exosomes play an important role in intercellular signaling and exert
      regulatory function by carrying bioactive molecules. This study investigated (1)
      the cardioprotective capabilities of exosomes derived from mesenchymal stem cells
      (MSCs) overexpressing GATA-4 (MSC(GATA-4)) and (2) its underlying regulatory
      mechanisms for expression of target proteins in recipient cells. METHODS AND
      RESULTS: Exosomes were isolated and purified from MSC(GATA-4) (Exo(GATA-4)) and
      control MSCs (Exo(Null)). Cell injury was investigated in primary cultured rat
      neonatal cardiomyocytes (CM) and in the rat heart. Exosomes contributed to
      increased CM survival, reduced CM apoptosis, and preserved mitochondrial membrane
      potential in CM cultured under a hypoxic environment. Direct intramyocardial
      transplantation of exosomes at the border of an ischemic region following
      ligation of the left anterior descending coronary artery significantly restored
      cardiac contractile function and reduced infarct size. Real-time PCR revealed
      that several anti-apoptotic miRs were highly expressed in Exo(GATA-4). Rapid
      internalization of Exo(GATA-4) by CM was documented using time-lapse imaging.
      Subsequent expression of these miRs, particularly miR-19a was higher in CM and in
      the myocardium treated with Exo(GATA-4) compared to those treated with Exo(Null).
      The enhanced protective effects observed in CM were diminished by the inhibition
      of miR-19a. The expression level of PTEN, a predicted target of miR-19a, was
      reduced in CM treated with Exo(GATA-4), which resulted in the activation of the
      Akt and ERK signaling pathways. CONCLUSIONS: Exo(GATA-4) upon transplantation in
      the damaged tissue mediate protection by releasing multiple miRs responsible for
      activation of the cell survival signaling pathway.

PMID- 25590963
TI  - Comparison of strain measurement from multimodality tissue tracking with strain
      encoding MRI and harmonic phase MRI in pulmonary hypertension.
AB  - BACKGROUND: Pixel-based multimodality tissue tracking (MTT) is a new noninvasive
      method for the quantification of cardiac deformation from cine image of MRI. The
      aim of this study is to validate bi-ventricular strain measurement by MTT
      compared to strain-encoding (SENC) MRI and harmonic phase (HARP) MRI in pulmonary
      hypertension (PH) patients. METHODS: In 45 subjects (30 PH patients and 15 normal
      subjects), RV and LV peak global longitudinal strains (Ell) were measured from
      long axis 4 chamber view using MTT. LV peak global circumferential strains (Ecc)
      by MTT were measured from short axis. For validation, RV and LV Ell by MTT were
      compared to measures by SENC-MRI from short axis, and LV Ecc by MTT was compared
      to measures by short axis tagged MRI analysis (HARP). Reproducibility of MTT was
      also determined. RESULTS: MTT quantified RV Ell correlated closely to those of
      SENC (r=0.72, p<0.001), with good limits of agreement. LV Ell quantified by MTT
      showed moderate correlation with SENC (r=0.57, p=0.001), and LV Ecc by MTT also
      showed moderate correlation with HARP (-16.9+/-4.1 vs -14.3+/-3.5, p<0.001 for
      all, r=0.60, p<0.001). RV Ell negatively correlated with RVEF (r=-0.53, p=0.001)
      and also positively correlated with mean PAP in PH patients (r=0.60, p=0.001).
      Strain measurement by MTT showed high reproducibility. CONCLUSIONS: We
      demonstrate that MTT is a reproducible tool for quantification of cardiac
      deformation using cine images in PH patients. Hence, it could serve as a new
      rapid and comprehensive technique for clinical assessment of regional cardiac
      function.

PMID- 25590965
TI  - Corrigendum. Noise effect on comfort in open-space offices: development of an
      assessment questionnaire.

PMID- 25590964
TI  - A phenotypic screen identifies microtubule plus end assembly regulators that can
      function in mitotic spindle orientation.
AB  - Proper regulation of microtubule dynamics during mitosis is essential for
      faithful chromosome segregation. In fact, recently we discovered increased
      microtubule plus end assembly rates that are frequently observed in human cancer
      cells as an important mechanism leading to whole chromosome missegregation and
      chromosomal instability (CIN). However, the genetic alterations responsible for
      increased microtubule polymerization rates in cancer cells remain largely
      unknown. The identification of such lesions is hampered by the fact that
      determining dynamic parameters of microtubules usually involves analyses of
      living cells, which is technically difficult to perform in large-scale screening
      settings. Therefore, we sought to identify alternative options to systematically
      identify regulators of microtubule plus end polymerization. Here, we introduce a
      simple and robust phenotypic screening assay that is based on the analyses of
      monopolar mitotic spindle structures that are induced upon inhibition of the
      mitotic kinesin Eg5/KIF11. We show that increased microtubule polymerization
      causes highly asymmetric monoasters in the presence of Eg5/KIF11 inhibition and
      this phenotype can be reliably assessed in living as well as in fixed cells.
      Using this assay we performed a siRNA screen, in which we identify several
      microtubule plus end binding proteins as well as centrosomal and cortex
      associated proteins as important regulators of microtubule plus end assembly.
      Interestingly, we demonstrate that a subgroup of these regulators function in the
      regulation of spindle orientation through their role in dampening microtubule
      plus end polymerization.

PMID- 25590966
TI  - The effects of the atypical antipsychotic asenapine in a strain-specific battery
      of tests for mania-like behaviors.
AB  - Asenapine is indicated for the treatment of schizophrenia and manic episodes in
      bipolar disorder (BPD). There is a paucity of information on the effects of
      asenapine in animal models of BPD, but such work is essential to discover its
      scope of effects and its mechanisms of therapeutic action. This study evaluated
      the effects of asenapine in a validated test battery for manic-like behaviors in
      Black Swiss mice. Male Black Swiss mice received asenapine at 0.03, 0.1, and 0.3
      mg/kg twice daily for 7 days and were tested for spontaneous activity, sweet
      solution preference, forced-swim test, social interaction, and amphetamine
      induced hyperactivity. Asenapine treatment resulted in dose-dependent, clinically
      relevant plasma levels. Asenapine, at the 0.1 and 0.3 mg/kg doses, reduced
      activity, with the 0.3 mg/kg dose also resulting in increased time in the center
      of an open field, increased immobility in the forced-swim test, and reduced
      amphetamine-induced hyperactivity. Asenapine exerted no effects in the social
      interaction or sweet solution preference tests. The results suggest that
      asenapine exerts antimanic-like effects in some of the behavioral tests performed
      in Black Swiss mice. These data support the utilization of asenapine in the
      treatment of BPD. 

PMID- 25590967
TI  - Fluvoxamine alleviates seizure activity and downregulates hippocampal GAP-43
      expression in pentylenetetrazole-kindled mice: role of 5-HT3 receptors.
AB  - Epilepsy has been documented to lead to many changes in the nervous system
      including cell loss and mossy fiber sprouting. Neuronal loss and aberrant
      neuroplastic changes in the dentate gyrus of the hippocampus have been identified
      in the pentylenetetrazole (PTZ) kindling model. Antiseizure activity of selective
      serotonin reuptake inhibitors has been reported in several studies. In the
      current study, the protective effect of fluvoxamine against PTZ-kindling was
      investigated in terms of seizure scores, neuronal loss, and regulation of
      hippocampal neuroplasticity. Further, the role of 5-HT3 receptors was determined.
      Kindling was induced by repeated injections of PTZ (35 mg/kg) thrice weekly, for
      a total of 13 injections. One hundred male albino mice were allocated into 10
      groups: (1) saline, (2) PTZ, (3) diazepam (1 mg/kg)+PTZ, (4-6) fluvoxamine (5, 10
      or 20 mg/kg)+PTZ, (7) ondansetron+fluvoxamine (20 mg/kg)+PTZ, (8) ondansetron+PTZ
      group, (9) ondansetron (2 mg/kg, i.p.)+saline, and (10) fluvoxamine (20
      mg/kg)+saline. PTZ-kindled mice showed high seizure activity, hippocampal
      neuronal loss, and expression of growth-associated phosphoprotein (GAP-43)
      compared with saline-treated mice. Repeated administration of fluvoxamine (20
      mg/kg) in PTZ-kindled mice suppressed seizure scores, protected against
      hippocampal neuronal loss, and downregulated GAP-43 expression, without producing
      any signs of the 5-HT syndrome in healthy rats. Importantly, pretreatment with a
      selective 5-HT3 receptor blocker (ondansetron) attenuated the aforementioned
      effects of fluvoxamine. In conclusion, the ameliorating effect of fluvoxamine on
      hippocampal neurons and neuroplasticity in PTZ-kindled mice was, at least in
      part, dependent on enhancement of hippocampal serotoninergic transmission at 5
      HT3 receptors. 

PMID- 25590969
TI  - Redox-tagged peptide for capacitive diagnostic assays.
AB  - Early detection assays play a key role in the successful treatment of most
      diseases. Redox capacitive biosensors were recently introduced as a potential
      electroanalytical assay platform for point-of-care applications but alternative
      surfaces (besides a mixed layer containing ferrocene and antibody receptive
      component) for recruiting important clinical biomarkers are still needed. Aiming
      to develop alternative receptive surfaces for this novel electrochemical
      biosensing platform, we synthesized a ferrocene redox-tagged peptide capable of
      self-assembly into metallic interfaces, a potentially useful biological surface
      functionalization for bedside diagnostic assays. As a proof of concept we used C
      reactive protein (CRP), as a model biomarker, and compared the obtained results
      to those of previously reported capacitive assays. The redox-tagged peptide
      approach shows a limit of detection of 0.8 nmol L(-1) (same as 94 ng mL(-1)) and
      a linear range (R(2)~98%) with the logarithm of the concentration of the analyte
      comprising 0.5-10.0 nmol L(-1), within a clinical relevant range for CRP.

PMID- 25590968
TI  - Postmarketing analysis of aflibercept-related sterile intraocular inflammation.
AB  - IMPORTANCE: Aflibercept-related sterile inflammation, an event that is poorly
      understood, has been the subject of ongoing postmarketing reports. OBJECTIVE: To
      analyze cases of aflibercept-related sterile inflammation reported to the
      American Society of Retina Specialists (ASRS) Therapeutic Surveillance Committee
      (TSC), an independent task force formed to monitor drug- and device-related
      safety events. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 56
      cases in 55 patients was performed of all cases of sterile inflammation after
      aflibercept injection that were voluntarily reported by 12 practices throughout
      the United States to the ASRS TSC from December 1, 2011, through February 12,
      2014. MAIN OUTCOMES AND MEASURES: Cases of aflibercept-related sterile
      inflammation were analyzed for baseline and demographic information, presenting
      symptoms and findings, visual acuity changes, injection technique, and management
      details. RESULTS: Among 56 reported cases of sterile inflammation, mean time to
      onset was 3.5 days (median, 2 days; range, 0-30 days). Most cases consisted of
      initial loss of vision and intraocular inflammation without prominent redness,
      severe pain, or hypopyon. Thirty-seven cases (66%) were treated with topical
      corticosteroids and/or observation alone. Mean time to resolution was 28.6 days
      (median, 28 days; range, 4-84 days). Although final vision was overall unchanged,
      some patients developed permanent vision loss, which may have resulted from
      inflammation and/or progression of the underlying disease. Age older than 80
      years was associated with worse visual outcomes. No difference in visual outcome
      was detected in patients with sterile inflammation undergoing topical therapy
      alone vs invasive procedures (vitreous biopsy and/or intravitreal antibiotic
      administration and/or vitrectomy). CONCLUSIONS AND RELEVANCE: With the largest
      number of reported cases of aflibercept-related sterile inflammation to our
      knowledge, this analysis suggests typical findings and an often favorable
      prognosis of this event. Analysis of real-world, postmarketing data has
      limitations, and these findings should be considered as hypothesis-generating
      assessments rather than a definitive reflection of this event or its typical
      course. Distinguishing sterile inflammation and infectious endophthalmitis at the
      time of presentation may often be difficult, and cautious evaluation and
      management of these patients are warranted. The ASRS TSC encourages active
      postmarketing surveillance by all physicians.

PMID- 25590970
TI  - Cyclodextrin supramolecular inclusion-enhanced pyrene excimer switching for time
      resolved fluorescence detection of biothiols in serum.
AB  - We report here an efficient pyrene excimer signaling-based time-resolved
      fluorescent sensor for the measurement of biothiols (cysteine (Cys), homocysteine
      (Hcy), glutathione (GSH)) in human serum based on thymine-Hg(2+)-thymine (T
      Hg(2+)-T) coordination chemistry and the inclusion interaction of cyclodextrin.
      The sensing mechanism of the approach is based on the competitive ligation of
      Hg(2+) ions by Hcy/Cys/GSH and T-T mismatches in a bis-pyrene-labeled DNA strand
      with the self-complementary 5' and 3' ends. The introduction of gamma
      cyclodextrin can provide cooperation for the molecular level space proximity of
      the two labeled pyrene molecules, moreover the hydrophobic cavity of gamma
      cyclodextrin can also offer protection for the pyrene dimer's emission from the
      quenching effect of environmental conditions and enhance the fluorescence
      intensity of the pyrene excimer. When the biothiols are not presented, the
      sensing ensemble is in the "off" state due to the long distance between the two
      labeled pyrene molecules resulted from the formation of a more stable T-Hg(2+)-T
      structure. While in the presence of biothiols, Hg(2+) interacts very strongly
      with thiol groups and the T-Hg(2+)-T structure is dehybridized, and then the
      pyrene excimer will be formed due to the self-complementary 5' and 3' ends of the
      DNA probe and the cooperation interaction of gamma-cyclodextrin to pyrene dimer,
      thus resulting in switching the sensing ensemble to the "on" state. In the
      optimum conditions described, the linear concentration range of 1.0-100 MUM with
      the limit of detection (LOD) of 0.36 MUM for GSH was obtained. Moreover, due to
      the much longer lifetime of the pyrene excimer fluorescence than those of the
      ubiquitous endogenous fluorescent components, the time-resolved fluorescence
      technique has been successfully used for application in complicated biological
      samples.

PMID- 25590971
TI  - Multiplex electrochemical DNA platform for femtomolar-level quantification of
      genetically modified soybean.
AB  - Current EU regulations on the mandatory labeling of genetically modified
      organisms (GMOs) with a minimum content of 0.9% would benefit from the
      availability of reliable and rapid methods to detect and quantify DNA sequences
      specific for GMOs. Different genosensors have been developed to this aim, mainly
      intended for GMO screening. A remaining challenge, however, is the development of
      genosensing platforms for GMO quantification, which should be expressed as the
      number of event-specific DNA sequences per taxon-specific sequences. Here we
      report a simple and sensitive multiplexed electrochemical approach for the
      quantification of Roundup-Ready Soybean (RRS). Two DNA sequences, taxon (lectin)
      and event-specific (RR), are targeted via hybridization onto magnetic beads. Both
      sequences are simultaneously detected by performing the immobilization,
      hybridization and labeling steps in a single tube and parallel electrochemical
      readout. Hybridization is performed in a sandwich format using signaling probes
      labeled with fluorescein isothiocyanate (FITC) or digoxigenin (Dig), followed by
      dual enzymatic labeling using Fab fragments of anti-Dig and anti-FITC conjugated
      to peroxidase or alkaline phosphatase, respectively. Electrochemical measurement
      of the enzyme activity is finally performed on screen-printed carbon electrodes.
      The assay gave a linear range of 2-250 pM for both targets, with LOD values of
      650 fM (160 amol) and 190 fM (50 amol) for the event-specific and the taxon
      specific targets, respectively. Results indicate that the method could be applied
      for GMO quantification below the European labeling threshold level (0.9%),
      offering a general approach for the rapid quantification of specific GMO events
      in foods.

PMID- 25590972
TI  - Label-free colorimetric detection of Hg2+ based on Hg2+-triggered exonuclease III
      assisted target recycling and DNAzyme amplification.
AB  - This work reported a label-free colorimetric assay for sensitive detection of
      Hg(2+) based on Hg(2+)-triggered hairpin DNA probe (H-DNA) termini-binding and
      exonuclease SH (Exo SH)-assisted target recycling, as well as hemin/G-quadruplex
      (DNAzyme) signal amplification. The specific binding of free Hg(2+) with the
      thymine-thymine (T-T) mismatches termini of H-DNA could immediately trigger the
      Exo SH digestion, and then set free G-quadruplex segments and Hg(2+). The Exo SH
      impellent recycling of ultratrace Hg(2+) produced numerous G-quadruplexes. The
      corresponding DNAzymes catalyzed efficiently the H2O2-mediated oxidation of the
      ABTS(2-) to the colored product in the presence of hemin. Using the color change
      as the output signal, and the Exo SH-aided Hg(2+) recycling and DNAzyme as the
      signal amplifier, the ultrasensitive assay system successfully achieved visual
      detection of Hg(2+) as low as 1.0 nM by the naked eye, and was suitable for field
      monitoring. The calibration curve was linear in the range of 50.0 pM to 20.0 nM
      for Hg(2+) (R=0.9962) with a detection limit of 10.0 pM. Moreover, this proposed
      strategy showed excellent selectivity, portability and low-cost, and was
      successfully applied to colorimetric detection of Hg(2+) in laboratory tap water
      and Jialing river water samples.

PMID- 25590974
TI  - Correction to "amyloid fibril nucleation: effect of amino Acid hydrophobicity".

PMID- 25590973
TI  - Analytical bioconjugates, aptamers, enable specific quantitative detection of
      Listeria monocytogenes.
AB  - As a major human pathogen in the Listeria genus, Listeria monocytogenes causes
      the bacterial disease listeriosis, which is a serious infection caused by eating
      food contaminated with the bacteria. We have developed an aptamer-based sandwich
      assay (ABSA) platform that demonstrates a promising potential for use in pathogen
      detection using aptamers as analytical bioconjugates. The whole-bacteria SELEX
      (WB-SELEX) strategy was adopted to generate aptamers with high affinity and
      specificity against live L. monocytogenes. Of the 35 aptamer candidates tested,
      LMCA2 and LMCA26 reacted to L. monocytogenes with high binding, and were
      consequently chosen as sensing probes. The ABSA platform can significantly
      enhance the sensitivity by employing a very specific aptamer pair for the
      sandwich complex. The ABSA platform exhibited a linear response over a wide
      concentration range of L. monocytogenes from 20 to 2*10(6) CFU per mL and was
      closely correlated with the following relationship: y=9533.3x+1542.3 (R(2)=0.99).
      Our proposed ABSA platform also provided excellent specificity for the tests to
      distinguish L. monocytogenes from other Listeria species and other bacterial
      genera (3 Listeria spp., 4 Salmonella spp., 2 Vibrio spp., 3 Escherichia coli and
      3 Shigella spp.). Improvements in the sensitivity and specificity have not only
      facilitated the reliable detection of L. monocytogenes at extremely low
      concentrations, but also allowed for the development of a 96-well plate-based
      routine assay platform for multivalent diagnostics.

PMID- 25590975
TI  - The effect of polydioxanone absorbable plates in septorhinoplasty for stabilizing
      caudal septal extension grafts.
AB  - IMPORTANCE: Caudal septal extension grafts (CSEGs) can be used to alter and
      secure nasal projection and length. Graft position and thickness play an
      important role in terms of both function and aesthetics. The limitations of
      harvesting cartilage from additional sites necessitate development of a more
      efficient method for securing CSEGs. OBJECTIVE: To assess the efficacy and safety
      of polydioxanone absorbable plates used in primary and revision septorhinoplasty.
      DESIGN, SETTING, AND PARTICIPANTS: We investigated all patients who underwent
      primary or revision septorhinoplasty with the use of absorbable plates to secure
      CSEGs at a tertiary academic medical center from 2010 to 2014. To standardize and
      objectify the symptoms of nasal obstruction, a validated quality-of-life
      instrument called the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire,
      with 5 questions on a scale of 0 to 4, was implemented preoperatively and
      postoperatively. Preoperative and multiple successive postoperative measurements
      of nasal length and projection were taken using 3dMDvultus imaging software. MAIN
      OUTCOMES AND MEASURES: Change in NOSE questionnaire score, change in nasal length
      and projection, and complications. RESULTS: There were no absorbable plate
      related complications in the 95 included patients. Comparing preoperative and
      postoperative NOSE questionnaire scores, there was a statistically significant
      improvement in all 5 categories: mean (SD) change of -1.42 (1.59) in congestion, 
      1.56 (1.53) in blockage or obstruction, -1.60 (1.54) in breathing through nose, 
      0.90 (1.54) in trouble sleeping, and -1.28 (1.46) in breathing during exercise (P
      < .001 for all) in the 50 patients with available data. In the 24 patients with
      greater than 180 days of follow-up, follow-up ranged from 183 to 717 days, and
      mean (SD) change in nasal length and projection was 0.64 (2.19) and 0.26 (0.96)
      mm, respectively, showing no statistically significant change over time (P = .17
      and .21, respectively). CONCLUSIONS AND RELEVANCE: In our study population, nasal
      length and projection maintained position over time when absorbable plates were
      used to secure CSEGs. Absorbable plates appear safe and effective when used to
      secure CSEGs and limit the requirement of harvesting additional cartilage. Nasal
      airway improvement can be obtained when absorbable plates are used to secure
      CSEGs. LEVEL OF EVIDENCE: 4.

PMID- 25590976
TI  - Symptom-driven idiopathic disease gene identification.
AB  - PURPOSE: Rare genetic variants are the major cause of Mendelian disorders, yet
      only half of described genetic diseases have been causally linked to a gene. In
      addition, the total number of rare genetic diseases is projected to be far
      greater than that of those already described. Whole-genome sequencing of patients
      with subsequent genetic and functional analysis is a powerful way to describe
      these gene anomalies. However, this approach results in tens to hundreds of
      candidate disease-causative genes, and the identification of additional
      individuals suffering from the same disorder can be difficult because of rarity
      and phenotypic heterogeneity. METHODS: We describe a genetic network-based method
      to rank candidate genes identified in family-based sequencing studies, termed
      phenotype informed network (PIN) ranking. Furthermore, we present a case study as
      an extension of the PIN ranking method in which disease symptoms drive the
      network ranking and identification of the disease-causative gene. RESULTS: We
      demonstrate, through simulation, that our method is capable of identifying the
      correct disease-causative gene in a majority of cases. PIN-rank is available at
      https://genomics.scripps.edu/pinrank/. CONCLUSION: We have developed a method to
      prioritize candidate disease-causative genes based on symptoms that would be
      useful for both the prioritization of candidates and the identification of
      additional subjects.

PMID- 25590977
TI  - Assessing the utility of confirmatory studies following identification of large
      scale genomic imbalances by microarray.
AB  - PURPOSE: The identification of clinically relevant genomic dosage anomalies
      assists in accurate diagnosis, prognosis, and medical management of affected
      individuals. Technological advancements within the field, such as the advent of
      microarray, have markedly increased the resolution of detection; however,
      clinical laboratories have maintained conventional techniques for confirmation of
      genomic imbalances identified by microarray to ensure diagnostic accuracy. In
      recent years the utility of this confirmatory testing of large-scale aberrations
      has been questioned but has not been scientifically addressed. METHODS: We
      retrospectively reviewed 519 laboratory cases with genomic imbalances meeting
      reportable criteria by microarray and subsequently confirmed with a second
      technology, primarily fluorescence in situ hybridization. RESULTS: All genomic
      imbalances meeting reportable criteria detected by microarray were confirmed with
      a second technology. Microarray analysis generated no false-positive results.
      CONCLUSION: Confirmatory testing of large-scale genomic imbalances (deletion of
      >=150 kb, duplication of >=500 kb) solely for the purpose of microarray
      verification may be unwarranted. In some cases, however, adjunct testing is
      necessary to overcome limitations inherent to microarray. A recommended clinical
      strategy for adjunct testing following identified genomic imbalances using
      microarray is detailed.

PMID- 25590978
TI  - Racial variation in frequency and phenotypes of APC and MUTYH mutations in 6,169
      individuals undergoing genetic testing.
AB  - PURPOSE: The aim of this study was to assess whether differences in frequency and
      phenotype of APC and MUTYH mutations exist among racially/ethnically diverse
      populations. METHODS: We studied 6,169 individuals with a personal and/or family
      history of colorectal cancer (CRC) and polyps. APC testing involved full
      sequencing/large rearrangement analysis (FS/LRA); MUTYH involved "panel testing"
      (for Y165C, G382D mutations) or FS/LRA performed by Myriad Genetics, a commercial
      laboratory. Subjects were identified as Caucasian, Asian, African American (AA),
      or other. Statistical tests included chi(2), Fisher's exact test, analysis of
      variance, and z approximation. RESULTS: Among participants, 17.5% had pathogenic
      APC mutations and 4.8% were biallelic MUTYH carriers. With regard to
      race/ethnicity, 18% were non-Caucasian, with >100 adenomas and younger ages at
      adenoma or CRC diagnosis (P < 0.0001) than Caucasians. The overall APC mutation
      rate was higher in Asians, AAs, and others as compared with Caucasians (25.2,
      30.9, 24, and 15.5%, respectively; P < 0.0001) but was similar in all groups when
      adjusted for polyp burden. More MUTYH biallelic carriers were Caucasian or other
      than Asian or AA (5, 7, 2.7, and 0.3%, respectively; P < 0.0001). Among
      Caucasians, 5% were biallelic carriers identified by panel testing versus 2%
      identified by sequencing/large rearrangement analysis (LRA) (P = 0.002). Among
      non-Caucasians, 3% undergoing panel testing were biallelic carriers versus 10%
      identified by sequencing/LRA (P < 0.0002). CONCLUSION: Non-Caucasians undergo
      genetic testing at more advanced stages of polyposis and/or are younger at
      CRC/polyp diagnosis. Restricted MUTYH analysis may miss significant numbers of
      biallelic carriers, particularly in non-Caucasians.

PMID- 25590980
TI  - Acceptability and feasibility of a virtual counselor (VICKY) to collect family
      health histories.
AB  - PURPOSE: To overcome literacy-related barriers in the collection of electronic
      family health histories, we developed an animated Virtual Counselor for Knowing
      your Family History, or VICKY. This study examined the acceptability and accuracy
      of using VICKY to collect family histories from underserved patients as compared
      with My Family Health Portrait (MFHP). METHODS: Participants were recruited from
      a patient registry at a safety net hospital and randomized to use either VICKY or
      MFHP. Accuracy was determined by comparing tool-collected histories with those
      obtained by a genetic counselor. RESULTS: A total of 70 participants completed
      this study. Participants rated VICKY as easy to use (91%) and easy to follow
      (92%), would recommend VICKY to others (83%), and were highly satisfied (77%).
      VICKY identified 86% of first-degree relatives and 42% of second-degree
      relatives; combined accuracy was 55%. As compared with MFHP, VICKY identified a
      greater number of health conditions overall (49% with VICKY vs. 31% with MFHP;
      incidence rate ratio (IRR): 1.59; 95% confidence interval (95% CI): 1.13-2.25; P
      = 0.008), in particular, hypertension (47 vs. 15%; IRR: 3.18; 95% CI: 1.66-6.10;
      P = 0.001) and type 2 diabetes (54 vs. 22%; IRR: 2.47; 95% CI: 1.33-4.60; P =
      0.004). CONCLUSION: These results demonstrate that technological support for
      documenting family history risks can be highly accepted, feasible, and effective.

PMID- 25590979
TI  - Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios.
AB  - PURPOSE: Despite the recognized clinical value of exome-based diagnostics,
      methods for comprehensive genomic interpretation remain immature. Diagnoses are
      based on known or presumed pathogenic variants in genes already associated with a
      similar phenotype. Here, we extend this paradigm by evaluating novel
      bioinformatics approaches to aid identification of new gene-disease associations.
      METHODS: We analyzed 119 trios to identify both diagnostic genotypes in known
      genes and candidate genotypes in novel genes. We considered qualifying genotypes
      based on their population frequency and in silico predicted effects we also
      characterized the patterns of genotypes enriched among this collection of
      patients. RESULTS: We obtained a genetic diagnosis for 29 (24%) of our patients.
      We showed that patients carried an excess of damaging de novo mutations in
      intolerant genes, particularly those shown to be essential in mice (P = 3.4 * 10(
      8)). This enrichment is only partially explained by mutations found in known
      disease-causing genes. CONCLUSION: This work indicates that the application of
      appropriate bioinformatics analyses to clinical sequence data can also help
      implicate novel disease genes and suggest expanded phenotypes for known disease
      genes. These analyses further suggest that some cases resolved by whole-exome
      sequencing will have direct therapeutic implications.

PMID- 25590984
TI  - Design, synthesis, and characterization of fatty acid derivatives of a dimeric
      peptide-based postsynaptic density-95 (PSD-95) inhibitor.
AB  - Dimeric peptide-based inhibitors of postsynaptic density-95 (PSD-95) can reduce
      ischemic brain damage and inflammatory pain in rodents. To modify the
      pharmacokinetic profile, we designed a series of fatty acid linked dimeric
      ligands, which potently inhibits PSD-95 and shows improved in vitro blood plasma
      stability. Subcutaneous administration in rats showed extended stability and
      sustained release of these ligands. This can facilitate new pharmacological uses
      of PSD-95 inhibitors and further exploration of PSD-95 as a drug target. 

PMID- 25590983
TI  - Divergent, coexisting Pseudomonas aeruginosa lineages in chronic cystic fibrosis
      lung infections.
AB  - RATIONALE: Pseudomonas aeruginosa, the predominant cause of chronic airway
      infections of patients with cystic fibrosis, exhibits extensive phenotypic
      diversity among isolates within and between sputum samples, but little is known
      about the underlying genetic diversity. OBJECTIVES: To characterize the
      population genetic structure of transmissible P. aeruginosa Liverpool Epidemic
      Strain in chronic infections of nine patients with cystic fibrosis, and infer
      evolutionary processes associated with adaptation to the cystic fibrosis lung.
      METHODS: We performed whole-genome sequencing of P. aeruginosa isolates and
      pooled populations and used comparative analyses of genome sequences including
      phylogenetic reconstructions and resolution of population structure from genome
      wide allele frequencies. MEASUREMENTS AND MAIN RESULTS: Genome sequences were
      obtained for 360 isolates from nine patients. Phylogenetic reconstruction of the
      ancestry of 40 individually sequenced isolates from one patient sputum sample
      revealed the coexistence of two genetically diverged, recombining lineages
      exchanging potentially adaptive mutations. Analysis of population samples for
      eight additional patients indicated coexisting lineages in six cases.
      Reconstruction of the ancestry of individually sequenced isolates from all
      patients indicated smaller genetic distances between than within patients in most
      cases. CONCLUSIONS: Our population-level analysis demonstrates that coexistence
      of distinct lineages of P. aeruginosa Liverpool Epidemic Strain within
      individuals is common. In several cases, coexisting lineages may have been
      present in the infecting inoculum or assembled through multiple transmissions.
      Divergent lineages can share mutations via homologous recombination, potentially
      aiding adaptation to the airway during chronic infection. The genetic diversity
      of this transmissible strain within infections, revealed by high-resolution
      genomics, has implications for patient segregation and therapeutic strategies.

PMID- 25590981
TI  - Family history and the natural history of colorectal cancer: systematic review.
AB  - PURPOSE: Family history of colorectal cancer (CRC) is a known risk factor for CRC
      and encompasses both genetic and shared environmental risks. METHODS: We
      conducted a systematic review to estimate the impact of family history on the
      natural history of CRC and adherence to screening. RESULTS: We found high
      heterogeneity in family-history definitions, the most common definition being one
      or more first-degree relatives. The prevalence of family history may be lower
      than the commonly cited 10%, and confirms evidence for increasing levels of risk
      associated with increasing family-history burden. There is evidence for higher
      prevalence of adenomas and of multiple adenomas in people with family history of
      CRC but no evidence for differential adenoma location or adenoma progression by
      family history. Limited data regarding the natural history of CRC by family
      history suggest a differential age or stage at cancer diagnosis and mixed
      evidence with respect to tumor location. Adherence to recommended colonoscopy
      screening was higher in people with a family history of CRC. CONCLUSION:
      Stratification based on polygenic and/or multifactorial risk assessment may
      mature to the point of displacing family history-based approaches, but for the
      foreseeable future, family history may remain a valuable clinical tool for
      identifying individuals at increased risk for CRC.

PMID- 25590985
TI  - Influence of functionalized pyridine ligands on the radio/chemical behavior of
      [M(I)(CO)3](+) (M = Re and (99m)Tc) 2 + 1 complexes.
AB  - While a number of chelate strategies have been developed for the organometallic
      precursor fac-[M(I)(OH2)3(CO)3](+) (M = Re, (99m)Tc), a unique challenge has been
      to improve the overall function and performance of these complexes for in vivo
      and in vitro applications. Since its discovery, fac-[M(I)(OH2)3(CO)3](+) has
      served as an essential scaffold for the development of new targeted (99m)Tc based
      radiopharmaceuticals due to its labile aquo ligands. However, the lipophilic
      nature of the fac-[M(I)(CO)3](+) core can influence the in vivo pharmacokinetics
      and biodistribution of the complexes. In an effort to understand and improve this
      behavior, monosubstituted pyridine ligands were used to assess the impact of
      donor nitrogen basicity on binding strength and stability of fac-[M(I)(CO)3](+)
      in a 2 + 1 labeling strategy. A series of Re and (99m)Tc complexes were
      synthesized with picolinic acid as a bidentate ligand and 4-substituted pyridine
      ligands. These complexes were designed to probe the effect of pKa from the
      monodentate pyridine ligand both at the macro scale and radiochemical
      concentrations. Comparison of X-ray structural data and radiochemical solution
      experiments clearly indicate an increase in overall yield and stability as
      pyridine basicity increased. 

PMID- 25590986
TI  - Enforced expression of Hoxa5 in haematopoietic stem cells leads to aberrant
      erythropoiesis in vivo.
AB  - Hoxa5 is preferentially expressed in haematopoietic stem cells (HSCs) and
      multipotent progenitor cells (MPPs), and is more highly expressed in expanding
      HSCs. To date, little is known regarding the role of Hoxa5 in HSCs and downstream
      progenitor cells in vivo. In this study, we show that increased expression of
      Hoxa5 in haematopoietic stem cells leads to aberrant erythropoiesis in vivo.
      Hoxa5 differentially modifies the cell cycle of HSCs and lineage committed
      progenitor cells, depending on the cellular context. Hoxa5 drives HSCs, but not
      MPPs, through the cell cycle and arrests erythroid progenitor cells in G0 phase.
      Although the HSC pool shrinks after overexpression of Hoxa5, HSCs sustain the
      abilities of self-renewal and multipotency. In vivo, Hoxa5 has two effects on
      erythropoiesis: it causes a predominance of mature erythroid lineage cells and
      the partial apoptosis of erythroid progenitors. RNA-seq indicates that multiple
      biological processes, including erythrocyte homeostasis, cell metabolism, and
      apoptosis, are modified by Hoxa5. The results of this study indicate that Hoxa5
      is a key regulator of the HSC cell cycle, and the inappropriate expression of
      Hoxa5 in lineage-committed progenitor cells leads to aberrant erythropoiesis. 

PMID- 25590987
TI  - Successful long-term management of invasive cerebral fungal infection following
      liver transplantation.
AB  - Central nervous system (CNS) infections after liver transplantation may be fungal
      in aetiology, with involvement from either common organisms such as Cryptococcus
      neoformans and Aspergillus spp. as well as less common organisms, such as the
      Mucorales and Scedosporium spp. Although the mortality of CNS fungal infections
      was nearly 100% in early series, more recent data has suggested that good
      outcomes can be achieved. This may be due to both improved diagnostic
      capabilities, such as the ability to obtain fungal susceptibilities and
      therapeutic drug levels, and improved therapeutic options, such as the newer
      triazoles- voriconazole and posaconazole. Due to improved outcomes, issues have
      now arisen around the long-term tolerability of these agents. The following two
      cases of invasive cerebral fungal infections following liver transplantation, one
      with Aspergillus flavus, and the other with Scedosporium boydii/apiospermum
      highlight the success that can be seen with the modern management of a previously
      fatal diagnosis. In particular, we highlight the issues around therapeutic
      monitoring and discontinuation of therapy. 

PMID- 25590988
TI  - The role of TRPV1 channels in carrageenan-induced mechanical hyperalgesia in
      mice.
AB  - Peripheral inflammation leads to ipsilateral and contralateral mechanical
      hyperalgesia. The transient receptor potential channel vanilloid type 1 (TRPV1),
      a nonselective cation channel expressed in mammalian primary sensory neurons and
      the spinal cord, may be involved in peripheral inflammation, but there is no
      consensus on the role of this channel in inflammation-induced mechanical
      hyperalgesia. Here, we examined the role of TRPV1 channels in carrageenan-induced
      mechanical hyperalgesia using wild-type and TRPV1-knockout (KO) mice and compared
      the results with those obtained in mice peripherally administered capsazepine, a
      TRPV1 antagonist, or capsaicin, a TRPV1 agonist. In the TRPV1-KO mice,
      ipsilateral mechanical hyperalgesia was significantly reduced during the acute
      phase (10-60 min), and the contralateral mechanical hyperalgesia nearly
      disappeared during both the acute and subacute phases. Blocking peripheral TRPV1
      using capsazepine before carrageenan administration resulted in similar effects
      as those observed in the TRPV1-KO mice, except that it was less effective against
      contralateral mechanical hyperalgesia during the subacute phase. In contrast,
      capsaicin remarkably decreased ipsilateral and contralateral mechanical
      hyperalgesia throughout both phases, but this analgesic effect was not observed
      in the TRPV1-KO mice. Thus, TRPV1 channels could be involved in the development
      of both ipsilateral and contralateral mechanical hyperalgesia after inflammation.
      Peripheral TRPV1 could participate in acute hyperalgesia, whereas central TRPV1
      may participate in subacute secondary hyperalgesia. Capsaicin potentially acts on
      both primary and secondary hyperalgesia in a TRPV1-dependent manner. 

PMID- 25590989
TI  - Surgical fixation of sternal fractures: preoperative planning and a safe surgical
      technique using locked titanium plates and depth limited drilling.
AB  - Different ways to stabilize a sternal fracture are described in literature.
      Respecting different mechanisms of trauma such as the direct impact to the
      anterior chest wall or the flexion-compression injury of the trunk, there is a
      need to retain each sternal fragment in the correct position while neutralizing
      shearing forces to the sternum. Anterior sternal plating provides the best
      stability and is therefore increasingly used in most cases. However, many
      surgeons are reluctant to perform sternal osteosynthesis due to possible
      complications such as difficulties in preoperative planning, severe injuries to
      mediastinal organs, or failure of the performed method. This manuscript describes
      one possible safe way to stabilize different types of sternal fractures in a step
      by step guidance for anterior sternal plating using low profile locking titanium
      plates. Before surgical treatment, a detailed survey of the patient and a three
      dimensional reconstructed computed tomography is taken out to get detailed
      information of the fracture's morphology. The surgical approach is usually a
      midline incision. Its position can be described by measuring the distance from
      upper sternal edge to the fracture and its length can be approximated by the
      summation of 60 mm for the basis incision, the thickness of presternal soft
      tissue and the greatest distance between the fragments in case of multiple
      fractures. Performing subperiosteal dissection along the sternum while reducing
      the fracture, using depth limited drilling, and fixing the plates prevents
      injuries to mediastinal organs and vessels. Transverse fractures and oblique
      fractures at the corpus sterni are plated longitudinally, whereas oblique
      fractures of manubrium, sternocostal separation and any longitudinally fracture
      needs to be stabilized by a transverse plate from rib to sternum to rib. Usually
      the high convenience of a patient is seen during follow up as well as a precise
      reconstruction of the sternal morphology. 

PMID- 25590990
TI  - Severe fungal sclerokeratitis caused by Metarhizium anisopliae: a case report and
      literature review.
AB  - To date, there has been only one published report on the infectious
      sclerokeratitis caused by Metarhizium anisopliae, which is an entomopathogenic
      fungus. Regarding corneal infection, three reports have been published to date.
      Although the prognoses of the corneal infections are favourable, prognosis when
      scleral infection is involved is very poor. A 76-year-old patient presented with
      foreign body sensation in the left eye. Microscopic examination with Fungi Flora
      Y staining of the corneal scraping revealed fungal infection. The conjunctiva was
      melted by the infection over a wide area. Although intensive medications were
      administered, an emergency surgery was necessary because scleral thinning,
      corneal perforation and lens prolapse occurred. The fungal isolate was identified
      as M. anisopliae by sequencing the internal transcribed spacer region. Herein, we
      report the second known case worldwide of M. anisopliae sclerokeratitis, and we
      review the literature related to the ocular infections. 

PMID- 25590991
TI  - Zebrafish (Danio rerio) eleutheroembryo-based procedure for assessing
      bioaccumulation.
AB  - This paper reports on the development and preliminary evaluation of a new
      bioaccumulation test based on the use of zebrafish (Danio renio) eleutheroembryos
      (72 h after hatching, corresponding to 144 h post fertilization, hpf) as an
      alternative to adult fish-based procedures for regulatory purposes regarding
      REACH application. The proposed test accomplished the OECD 305 guideline and
      consists of a 48 h uptake period followed by a 24 h depuration step.
      Bioaccumulation experiments were performed for a selected of hyper hydrophobic
      chemicals (log Kow> 7.6), that is, PCB 136 and PBDE 154 at two concentration
      levels corresponding roughly to 1% and 0.1% the chemicals LC50(nominal
      concentrations of 4.0 and 12.0 MUg/L for PCB 136, and 1.0 and 5.0 MUg/L PBDE 154,
      respectively). Toxicokinetic models were used to calculate the bioconcentration
      factors (BCFs) based on of the chemical concentrations found in the contaminated
      eleutheroembryos and their surrounding media. The experimentally determined
      accumulation profiles show bioaccumulation by zebrafish eleutheroembryos of both
      chemicals, and that the process is more complex than simple water-lipid
      partition. Calculated log BCFs using a first-order accumulation model(3.97 and
      3.73 for PCB 136, and 3.95 and 4.29 for PBDE 154) were in the range of those
      previously reported in the literature. The suitability of this new nonprotected
      life stage bioaccumulation protocol for BCF estimation was evaluated by
      application to widely divergent micropollutants with different accumulation
      mechanisms. The results were compared with those in the MITE-NITE database for
      adult rice fish (Oryzias latipes). 

PMID- 25590992
TI  - Synthesis of unsymmetrical pyrazines based on alpha-diazo oxime ethers.
AB  - Synthesis of unsymmetrically substituted pyrazines has been a challenge. The
      reactivity of alpha-imino carbenoids derived from alpha-diazo oxime ethers has
      been exploited for pyrazine synthesis, in which the reaction of alpha-diazo oxime
      ethers with 2H-azirines provides highly substituted pyrazines in good to
      excellent yields. 

PMID- 25590993
TI  - What's new in Shock? February 2015.

PMID- 25590995
TI  - Vertical heterostructure of two-dimensional MoS2 and WSe2 with vertically aligned
      layers.
AB  - Two-dimensional (2D) layered materials consist of covalently bonded 2D atomic
      layers stacked by van der Waals interactions. Such anisotropic bonding nature
      gives rise to the orientation-dependent functionalities of the 2D layered
      materials. Different from most studies of 2D materials with their atomic layers
      parallel to substrate, we have recently developed layer vertically aligned 2D
      material nanofilms. Built on these developments, here, we demonstrate the
      synthesis of vertical heterostructure of n-type MoS2 and p-type WSe2 with
      vertically aligned atomic layers. Thin film of MoS2/WSe2 vertical structure was
      successfully synthesized without significant alloy formation. The heterostructure
      synthesis is scalable to a large area over 1 cm(2). We demonstrated the pn
      junction diode behavior of the heterostructure device. This novel device geometry
      opens up exciting opportunities for a variety of electronic and optoelectronic
      devices, complementary to the recent interesting vertical heterostructures with
      horizontal atomic layers. 

PMID- 25590994
TI  - Evaluation of stem cell properties in human ovarian carcinoma cells using multi
      and single cell-based spheres assays.
AB  - Years of research indicates that ovarian cancers harbor a heterogeneous mixture
      of cells including a subpopulation of so-called "cancer stem cells" (CSCs)
      responsible for tumor initiation, maintenance and relapse following conventional
      chemotherapies. Identification of ovarian CSCs is therefore an important goal. A
      commonly used method to assess CSC potential in vitro is the spheres assay in
      which cells are plated under non-adherent culture conditions in serum-free medium
      supplemented with growth factors and sphere formation is scored after a few days.
      Here, we review currently available protocols for human ovarian cancer spheres
      assays and perform a side-by-side analysis between commonly used multi cell-based
      assays and a more accurate system based on single cell plating. Our results
      indicate that both multi cell-based as well as single cell-based spheres assays
      can be used to investigate sphere formation in vitro. The more laborious and
      expensive single cell-based assays are more suitable for functional assessment of
      individual cells and lead to overall more accurate results while multi cell-based
      assays can be strongly influenced by the density of plated cells and require
      titration experiments upfront. Methylcellulose supplementation to multi cell
      based assays can be effectively used to reduce mechanical artifacts. 

PMID- 25590996
TI  - Copy number variation detection using SNP genotyping arrays in three Chinese pig
      breeds.
AB  - We performed genome-wide CNV detection based on SNP genotyping data of 96 Chinese
      native Tibetan, Dahe and Wuzhishan pigs. These pigs are particularly interesting
      because of their excellent adaptation to hypoxia or small body size, which
      facilitates the use of them as models of different human diseases in addition to
      valuable agricultural animals. A total of 105 CNV regions (CNVRs) were
      identified, encompassing 16.71 Mb of the pig genome. Seven of 10 (70%) CNVRs
      selected randomly were validated by quantitative real-time PCR. Comparison with
      previous studies revealed 25 (23.81%) novel CNVRs, indicating that CNV coverage
      of the pig genome is still incomplete and there exists large diversity between
      pig breeds. Functional analysis of genes located in these CNVRs confirmed the
      high representation of genes involved in sensory perception, neurological system
      processes and other basic metabolic processes. In addition, the majority of these
      CNVRs were detected to span reported pig QTL that affect various traits, which
      highlighted three biologically interesting genes with copy number changes (i.e.,
      ANKRD34B, FAM110B and ABCG1). These genes may have economic importance in pig
      breeding and are worth being further investigated. We also obtained some CNVRs
      harboring genes that had human orthologs involved in human diseases such as
      cardiovascular disease and Alzheimer's disease. The findings of this study are a
      significant extension of the coverage of CNVRs in the pig genome and provide
      valuable resources for follow-up-associated studies of CNVs in pig complex traits
      as well as important implications of human diseases. 

PMID- 25590997
TI  - An analytical method for 14C in environmental water based on a wet-oxidation
      process.
AB  - An analytical method for (14)C in environmental water based on a wet-oxidation
      process was developed. The method can be used to determine the activity
      concentrations of organic and inorganic (14)C in environmental water, or total
      (14)C, including in drinking water, surface water, rainwater and seawater. The
      wet-oxidation of the organic component allows the conversion of organic carbon to
      an inorganic form, and the extraction of the inorganic (14)C can be achieved by
      acidification and nitrogen purging. Environmental water with a volume of 20 L can
      be used for the wet-oxidation and extraction, and a detection limit of about 0.02
      Bq/g(C) can be achieved for water with carbon content above 15 mg(C)/L, obviously
      lower than the natural level of (14)C in the environment. The collected carbon is
      sufficient for measurement with a low level liquid scintillation counter (LSC)
      for typical samples. Extraction or recovery experiments for inorganic carbon and
      organic carbon from typical materials, including analytical reagents of organic
      benzoquinone, sucrose, glutamic acid, nicotinic acid, humic acid, ethane diol, et
      cetera., were conducted with excellent results based on measurement on a total
      organic carbon analyzer and LSC. The recovery rate for inorganic carbon ranged
      tween 98.7%-99.0% with a mean of 98.9(+/- 0.1)%, for organic carbon recovery
      ranged between 93.8% and 100.0% with a mean of 97.1(+/- 2.6)%. Verification and
      an uncertainty budget of the method are also presented for a representative
      environmental water. The method is appropriate for (14)C analysis in
      environmental water, and can be applied also to the analysis of liquid effluent
      from nuclear facilities.

PMID- 25590998
TI  - Non-invasive imaging and analysis of cerebral ischemia in living rats using
      positron emission tomography with 18F-FDG.
AB  - Stroke is the third leading cause of death among Americans 65 years of age or
      older(1). The quality of life for patients who suffer from a stroke fails to
      return to normal in a large majority of patients(2), which is mainly due to
      current lack of clinical treatment for acute stroke. This necessitates
      understanding the physiological effects of cerebral ischemia on brain tissue over
      time and is a major area of active research. Towards this end, experimental
      progress has been made using rats as a preclinical model for stroke,
      particularly, using non-invasive methods such as (18)F-fluorodeoxyglucose (FDG)
      coupled with Positron Emission Tomography (PET) imaging(3,10,17). Here we present
      a strategy for inducing cerebral ischemia in rats by middle cerebral artery
      occlusion (MCAO) that mimics focal cerebral ischemia in humans, and imaging its
      effects over 24 hr using FDG-PET coupled with X-ray computed tomography (CT) with
      an Albira PET-CT instrument. A VOI template atlas was subsequently fused to the
      cerebral rat data to enable a unbiased analysis of the brain and its sub
      regions(4). In addition, a method for 3D visualization of the FDG-PET-CT time
      course is presented. In summary, we present a detailed protocol for initiating,
      quantifying, and visualizing an induced ischemic stroke event in a living Sprague
      Dawley rat in three dimensions using FDG-PET. 

PMID- 25591000
TI  - Isolation and intravenous injection of murine bone marrow derived monocytes.
AB  - As a subtype of leukocytes and progenitors of macrophages, monocytes are involved
      in many important processes of organisms and are often the subject of various
      fields in biomedical science. The method described below is a simple and
      effective way to isolate murine monocytes from heterogeneous bone marrow. Bone
      marrow from the femur and tibia of Balb/c mice is harvested by flushing with
      phosphate buffered saline (PBS). Cell suspension is supplemented with macrophage
      colony stimulating factor (M-CSF) and cultured on ultra-low attachment surfaces
      to avoid adhesion-triggered differentiation of monocytes. The properties and
      differentiation of monocytes are characterized at various intervals. Fluorescence
      activated cell sorting (FACS), with markers like CD11b, CD115, and F4/80, is used
      for phenotyping. At the end of cultivation, the suspension consists of 45%+/- 12%
      monocytes. By removing adhesive macrophages, the purity can be raised up to 86%+/
      6%. After the isolation, monocytes can be utilized in various ways, and one of
      the most effective and common methods for in vivo delivery is intravenous tail
      vein injection. This technique of isolation and application is important for
      mouse model studies, especially in the fields of inflammation or immunology.
      Monocytes can also be used therapeutically in mouse disease models. 

PMID- 25591001
TI  - Image-based flow cytometry technique to evaluate changes in granulocyte function
      in vitro.
AB  - Granulocytes play a key role in the body's innate immune response to bacterial
      and viral infections. While methods exist to measure granulocyte function, in
      general these are limited in terms of the information they can provide. For
      example, most existing assays merely provide a percentage of how many
      granulocytes are activated following a single, fixed length incubation.
      Complicating matters, most assays focus on only one aspect of function due to
      limitations in detection technology. This report demonstrates a technique for
      simultaneous measurement of granulocyte phagocytosis of bacteria and oxidative
      burst. By measuring both of these functions at the same time, three unique
      phenotypes of activated granulocytes were identified: 1) Low Activation (minimal
      phagocytosis, no oxidative burst), 2) Moderate Activation (moderate phagocytosis,
      some oxidative burst, but no co-localization of the two functional events), and
      3) High Activation (high phagocytosis, high oxidative burst, co-localization of
      phagocytosis and oxidative burst). A fourth population that consisted of
      inactivated granulocytes was also identified. Using assay incubations of 10, 20,
      and 40-min the effect of assay incubation duration on the redistribution of
      activated granulocyte phenotypes was assessed. A fourth incubation was completed
      on ice as a control. By using serial time incubations, the assay may be able to
      able to detect how a treatment spatially affects granulocyte function. All
      samples were measured using an image-based flow cytometer equipped with a
      quantitative imaging (QI) option, autosampler, and multiple lasers (488, 642, and
      785 nm). 

PMID- 25590999
TI  - The melanoma-associated antigen 1 (MAGEA1) protein stimulates the E3 ubiquitin
      ligase activity of TRIM31 within a TRIM31-MAGEA1-NSE4 complex.
AB  - The MAGE (Melanoma-associated antigen) protein family members are structurally
      related to each other by a MAGE-homology domain comprised of 2 winged helix
      motifs WH/A and WH/B. This family specifically evolved in placental mammals
      although single homologs designated NSE3 (non-SMC element) exist in most
      eukaryotes. NSE3, together with its partner proteins NSE1 and NSE4 form a tight
      subcomplex of the structural maintenance of chromosomes SMC5-6 complex.
      Previously, we showed that interactions of the WH/B motif of the MAGE proteins
      with their NSE4/EID partners are evolutionarily conserved (including the MAGEA1
      NSE4 interaction). In contrast, the interaction of the WH/A motif of NSE3 with
      NSE1 diverged in the MAGE paralogs. We hypothesized that the MAGE paralogs
      acquired new RING-finger-containing partners through their evolution and form
      MAGE complexes reminiscent of NSE1-NSE3-NSE4 trimers. In this work, we employed
      the yeast 2-hybrid system to screen a human RING-finger protein library against
      several MAGE baits. We identified a number of potential MAGE-RING interactions
      and confirmed several of them (MDM4, PCGF6, RNF166, TRAF6, TRIM8, TRIM31, TRIM41)
      in co-immunoprecipitation experiments. Among these MAGE-RING pairs, we chose to
      examine MAGEA1-TRIM31 in detail and showed that both WH/A and WH/B motifs of
      MAGEA1 bind to the coiled-coil domain of TRIM31 and that MAGEA1 interaction
      stimulates TRIM31 ubiquitin-ligase activity. In addition, TRIM31 directly binds
      to NSE4, suggesting the existence of a TRIM31-MAGEA1-NSE4 complex reminiscent of
      the NSE1-NSE3-NSE4 trimer. These results suggest that MAGEA1 functions as a co
      factor of TRIM31 ubiquitin-ligase and that the TRIM31-MAGEA1-NSE4 complex may
      have evolved from an ancestral NSE1-NSE3-NSE4 complex.

PMID- 25591002
TI  - Protein-protein interactions affect alpha helix stability in crowded
      environments.
AB  - The dense, heterogeneous cellular environment is known to affect protein
      stability through interactions with other biomacromolecules. The effect of
      excluded volume due to these biomolecules, also known as crowding agents, on a
      protein of interest, or test protein, has long been known to increase the
      stability of a test protein. Recently, it has been recognized that attractive
      protein-crowder interactions play an important role. These interactions affect
      protein stability and can destabilize the test protein. However, most
      computational work investigating the role of attractive interactions has used
      spherical crowding agents and has neglected the specific roles of crowding agent
      hydrophobicity and hydrogen bonding. Here we use multicanonical molecular
      dynamics and a coarse-grained protein model to study the folding thermodynamics
      of a small helical test protein in the presence of crowding agents that are
      themselves proteins. Our results show that the stability of the test protein
      depends on the hydrophobicity of the crowding agents. For low values of crowding
      agent hydrophobicity, the excluded volume effect is dominant, and the test
      protein is stabilized relative to the dilute solution. For intermediate values of
      the crowding agent hydrophobicity, the test protein is destabilized by favorable
      side chain-side chain interactions stabilizing the unfolded states. For high
      values of the crowding agent hydrophobicity, the native state is stabilized by
      the strong intermolecular attractions, causing the formation of a packed
      structure that increases the stability of the test protein through favorable side
      chain-side chain interactions. In addition, increasing crowding agent
      hydrophobicity increases the "foldability" of the test protein and alters the
      potential energy landscape by simultaneously deepening the basins corresponding
      to the folded and unfolded states and increasing the energy barrier between them.

PMID- 25591004
TI  - Magnetic anisotropy in "scorpionate" first-row transition-metal complexes: a
      theoretical investigation.
AB  - In this work we have analyzed in detail the magnetic anisotropy in a series of
      hydrotris(pyrazolyl)borate (Tp(-)) metal complexes, namely [VTpCl](+),
      [CrTpCl](+), [MnTpCl](+), [FeTpCl], [CoTpCl], and [NiTpCl], and their substituted
      methyl and tert-butyl analogues with the goal of observing the effect of the
      ligand field on the magnetic properties. In the [VTpCl](+), [CrTpCl](+),
      [CoTpCl], and [NiTpCl] complexes, the magnetic anisotropy arises as a consequence
      of out-of-state spin-orbit coupling, and covalent changes induced by the
      substitution of hydrogen atoms on the pyrazolyl rings does not lead to drastic
      changes in the magnetic anisotropy. On the other hand, much larger magnetic
      anisotropies were predicted in complexes displaying a degenerate ground state,
      namely [MnTpCl](+) and [FeTpCl], due to in-state spin-orbit coupling. The
      anisotropy in these systems was shown to be very sensitive to perturbations, for
      example, chemical substitution and distortions due to the Jahn-Teller effect. We
      found that by substituting the hydrogen atoms in [MnTpCl](+) and [FeTpCl] by
      methyl and tert-butyl groups, certain covalent contributions to the magnetic
      anisotropy energy (MAE) could be controlled, thereby achieving higher values.
      Moreover, we showed that the selection of ion has important consequences for the
      symmetry of the ground spin-orbit term, opening the possibility of achieving zero
      magnetic tunneling even in non-Kramers ions. We have also shown that substitution
      may also contribute to a quenching of the Jahn-Teller effect, which could
      significantly reduce the magnetic anisotropy of the complexes studied.

PMID- 25591009
TI  - Numerically testing phenomenological models for conductance of a solid-state
      nanopore.
AB  - The ionic conductance of a solid-state nanopore plays an important role in
      analyzing biomolecules transported through the pore. The phenomenological pore
      conductance is assumed to be a sum of three contributions: bulk, surface (for a
      charged nanopore) and access ones. Despite being commonly used, phenomenological
      results were not rigorously derived in theory and their accuracies have not been
      tested yet. By carrying out numerical modeling on the nanopore conductance, I
      show that both the ion concentration and the surface charge can affect the
      accuracy. For a charged solid-state nanopore solvated in an intermediate-ion
      concentration electrolyte (e.g. 50 mM), the phenomenological result can be
      substantially larger than the numerically calculated one. The criteria for
      properly applying phenomenological results are provided. 

PMID- 25591003
TI  - Structural convergence of unstructured p53 family transactivation domains in MDM2
      recognition.
AB  - The p53, p63, and p73 proteins belong to the p53 family of transcription factors,
      which play key roles in tumor suppression. Although the transactivation domains
      (TADs) of the p53 family are intrinsically disordered, these domains are commonly
      involved in the regulatory interactions with mouse double minute 2 (MDM2). In
      this study, we determined the solution structure of the p73TAD peptide in complex
      with MDM2 using NMR spectroscopy and biophysically characterized the interactions
      between the p53 family TAD peptides and MDM2. In combination with mutagenesis
      data, the complex structures revealed remarkably close mimicry of the MDM2
      recognition mechanism among the p53 family TADs. Upon binding with MDM2, the
      intrinsically disordered p73TAD and p63TAD peptides adopt an amphipathic alpha
      helical conformation, which is similar to the conformation of p53TAD, although
      the alpha-helical content induced by MDM2 binding varies. With isothermal
      titration calorimetry (ITC) and circular dichroism (CD) data, our biophysical
      characterization showed that p73TAD resembles p53TAD more closely than p63TAD in
      terms of helical stability, MDM2 binding affinity, and phosphorylation effects on
      MDM2 binding. Therefore, our structural information may be useful in establishing
      alternative anticancer strategies that exploit the activation of the p73 pathway
      against human tumors bearing p53 mutations. 

PMID- 25591008
TI  - Heliotropium europaeum poisoning in cattle and analysis of its pyrrolizidine
      alkaloid profile.
AB  - Pyrrolizidine alkaloids (PAs) are carcinogenic and genotoxic phytochemicals found
      exclusively in angiosperms. The ingestion of PA-containing plants often results
      in acute and chronic toxicities in man and livestock, targeting mainly the liver.
      During February 2014, a herd of 15-18-month-old mixed-breed beef cattle (n = 73)
      from the Galilee region in Israel was accidently fed hay contaminated with 12%
      Heliotropium europaeum (average total PA intake was 33 mg PA/kg body weight/d).
      After 42 d of feed ingestion, sudden death occurred over a time period of 63 d
      with a mortality rate of 33%. Necropsy and histopathological examination revealed
      fibrotic livers and moderate ascites, as well as various degrees of hyperplasia
      and fibrosis of bile duct epithelial cells. Elevated gamma-glutamyl-transferase
      and alkaline phosphatase levels were indicative of severe liver damage.
      Comprehensive PA profile determination of the contaminated hay and of native H.
      europaeum by LC-MS/MS revealed the presence of 30 PAs and PA-N-oxides, including
      several newly reported PAs and PA-N-oxides of the rinderine and heliosupine
      class. Heliotrine- and lasiocarpine-type PAs constituted 80% and 18% of the total
      PAs, respectively, with the N-oxides being the most abundant form (92%). The PA
      profile of the contaminated hay showed very strong resemblance to that of H.
      europaeum.

PMID- 25591010
TI  - One-pot chemical synthesis of small ubiquitin-like modifier protein-peptide
      conjugates using bis(2-sulfanylethyl)amido peptide latent thioester surrogates.
AB  - Small ubiquitin-like modifier (SUMO) post-translational modification (PTM) of
      proteins has a crucial role in the regulation of important cellular processes.
      This protocol describes the chemical synthesis of functional SUMO-peptide
      conjugates. The two crucial stages of this protocol are the solid-phase synthesis
      of peptide segments derivatized by thioester or bis(2-sulfanylethyl)amido (SEA)
      latent thioester functionalities and the one-pot assembly of the SUMO-peptide
      conjugate by a sequential native chemical ligation (NCL)/SEA native peptide
      ligation reaction sequence. This protocol also enables the isolation of a SUMO
      SEA latent thioester, which can be attached to a target peptide or protein in a
      subsequent step. It is compatible with 9-fluorenylmethoxycarbonyl (Fmoc)
      chemistry, and it gives access to homogeneous, reversible and functional SUMO
      conjugates that are not easily produced using living systems. The synthesis of
      SUMO-peptide conjugates on a milligram scale takes 20 working days. 

PMID- 25591011
TI  - A 12-step user guide for analyzing voxel-wise gray matter asymmetries in
      statistical parametric mapping (SPM).
AB  - Voxel-based morphometry (VBM) has been proven capable of capturing cerebral gray
      matter asymmetries with a high (voxel-wise) regional specificity. However, a
      standardized reference on how to conduct voxel-wise asymmetry analyses is
      missing. This protocol provides the scientific community with a carefully
      developed guide describing, in 12 distinct steps, how to take structural images
      from data pre-processing, via statistical analysis, to the final interpretation
      of the significance maps. Key adaptations compared with the standard VBM workflow
      involve establishing a voxel-wise hemispheric correspondence, capturing the
      direction and degree of asymmetry and preventing a blurring of information across
      hemispheres. The workflow incorporates the most recent methodological
      developments, including high-dimensional spatial normalization and partial volume
      estimations. Although the protocol is primarily designed to enable relatively
      inexperienced users to conduct a voxel-based asymmetry analysis on their own, it
      may also be useful to experienced users who wish to efficiently adapt their
      existing scripts or pipelines. 

PMID- 25591013
TI  - Efficiency of hole transfer from photoexcited quantum dots to covalently linked
      molecular species.
AB  - Hole transfer from high photoluminescence quantum yield (PLQY) CdSe-core CdS
      shell semiconductor nanocrystal quantum dots (QDs) to covalently linked molecular
      hole acceptors is investigated. (1)H NMR is used to independently calibrate the
      average number of hole acceptor molecules per QD, N, allowing us to measure PLQY
      as a function of N, and to extract the hole transfer rate constant per acceptor,
      kht. This value allows for reliable comparisons between nine different donor
      acceptor systems with variant shell thicknesses and acceptor ligands, with kht
      spanning over 4 orders of magnitude, from single acceptor time constants as fast
      as 16 ns to as slow as 0.13 ms. The PLQY variation with acceptor coverage for all
      kht follows a universal equation, and the shape of this curve depends critically
      on the ratio of the total hole transfer rate to the sum of the native
      recombination rates in the QD. The dependence of kht on the CdS thickness and the
      chain length of the acceptor is investigated, with damping coefficients beta
      measured to be (0.24 +/- 0.025) A(-1) and (0.85 +/- 0.1) A(-1) for CdS and the
      alkyl chain, respectively. We observe that QDs with high intrinsic PLQYs (>79%)
      can donate holes to surface-bound molecular acceptors with efficiencies up to 99%
      and total hole transfer time constants as fast as 170 ps. We demonstrate the
      merits of a system where ill-defined nonradiative channels are suppressed and
      well-defined nonradiative channels are engineered and quantified. These results
      show the potential of QD systems to drive desirable oxidative chemistry without
      undergoing oxidative photodegradation. 

PMID- 25591012
TI  - Drug modulation of water-heme interactions in low-spin P450 complexes of CYP2C9d
      and CYP125A1.
AB  - Azoles and pyridines are commonly incorporated into small molecule inhibitor
      scaffolds that target cytochromes P450 (CYPs) as a strategy to increase drug
      binding affinity, impart isoform-dependent selectivity, and improve metabolic
      stability. Optical absorbance spectra of the CYP-inhibitor complex are widely
      used to infer whether these inhibitors are ligated directly to the heme iron as
      catalytically inert, low-spin (type II) complexes. Here, we show that the low
      spin complex between a drug-metabolizing CYP2C9 variant and 4-(3-phenylpropyl)-1H
      1,2,3-triazole (PPT) retains an axial water ligand despite exhibiting elements of
      "classic" type II optical behavior. Hydrogens of the axial water ligand are
      observed by pulsed electron paramagnetic resonance (EPR) spectroscopy for both
      inhibitor-free and inhibitor-bound species and show that inhibitor binding does
      not displace the axial water. A (15)N label incorporated into PPT is 0.444 nm
      from the heme iron, showing that PPT is also in the active site. The reverse type
      I inhibitor, LP10, of CYP125A1 from Mycobacterium tuberculosis, known from X-ray
      crystal structures to form a low-spin water-bridged complex, is found by EPR and
      by visible and near-infrared magnetic circular dichroism spectroscopy to retain
      the axial water ligand in the complex in solution. 

PMID- 25591015
TI  - Oral potentially malignant disorders in a large dental population.
AB  - OBJECTIVES: Oral cancer (OC) may be preceded by clinically evident oral
      potentially malignant disorders (OPMDs). Oral carcinogenesis is a multistep
      process that begins as epithelial hyperplasia and progresses to oral epithelial
      dysplasia and finally to fully malignant phenotypes. The aim of our study was to
      estimate the prevalence of OPMDs in a large population of dental patients.
      METHODS: Patients were seen in the Oral Diagnosis and Oral Medicine clinics at
      Boston University Henry M. Goldman School of Dental Medicine between July 2013
      and February 2014 and received a comprehensive oral examination to identify any
      possible mucosal lesions. Patients with a suspected OPMD (submucous fibrosis,
      oral lichen planus, leukoplakia and erythroplakia) that did not resolve in 2-3
      weeks received a biopsy for definitive diagnosis. Logistic regression models were
      used to explore the relationship between OPMDs and associated risk factors.
      RESULTS: A total of 3,142 patients received a comprehensive oral examination
      [median age: 43 (range: 18-97); 54.3% females]. Among these, 4.5% had an oral
      mucosal lesion with 0.9% being an OPMD (one submucous fibrosis, three epithelial
      dysplasias, fourteen with hyperkeratosis/epithelial hyperplasia and nine with
      oral lichen planus). Males and current smokers were associated with higher odds
      of having OPMD (OR 1.7, 95% CI 0.8-3.8; OR 1.9, 95% CI 0.8-4.1). Increasing age
      was associated with having OPMDs (p<0.01). CONCLUSION: Optimal oral visual
      screening for OC remains a simple and essential tool to identify any suspicious
      lesions and potentially increase survival. Although OPMDs were rare, our results
      confirm the importance of a thorough chairside screening by dentists and dental
      students to detect any mucosal changes.

PMID- 25591016
TI  - Telegenetics: application of a tele-education program in genetic syndromes for
      Brazilian students.
AB  - With the high occurrence of genetic anomalies in Brazil and the manifestations of
      communication disorders associated with these conditions, the development of
      educative actions that comprise these illnesses can bring unique benefits in the
      identification and appropriate treatment of these clinical pictures. Objective
      The aim of this study was to develop and analyze an educational program in
      genetic syndromes for elementary students applied in two Brazilian states, using
      an Interactive Tele-education model. Material and Methods The study was carried
      out in 4 schools: two in the state of Sao Paulo, Southeast Region, Brazil, and
      two in the state of Amazonas, North Region, Brazil. Forty-five students, both
      genders, aged between 13 and 14 years, of the 9th grade of the basic education of
      both public and private system, were divided into two groups: 21 of Sao Paulo
      Group (SPG) and 24 of Amazonas Group (AMG). The educational program lasted about
      3 months and was divided into two stages including both classroom and distance
      activities on genetic syndromes. The classroom activity was carried out
      separately in each school, with expository lessons, graphs and audiovisual
      contents. In the activity at a distance the educational content was presented to
      students by means of the Interactive Tele-education model. In this stage, the
      students had access a Cybertutor, using the Young Doctor Project methodology. In
      order to measure the effectiveness of the educational program, the Problem
      Situation Questionnaire (PSQ) and the Web Site Motivational Analysis Checklist
      adapted (FPM) were used. Results The program developed was effective for
      knowledge acquisition in 80% of the groups. FPM showed a high satisfaction index
      from the participants in relation to the Interactive Tele-education, evaluating
      the program as "awesome course". No statistically significant differences between
      the groups regarding type of school or state were observed. Conclusion Thus, the
      Tele-Education Program can be used as a tool for educational purposes in genetic
      syndromes of other populations, in several regions of Brazil. 

PMID- 25591017
TI  - Evaluation of caries-associated virulence of biofilms from Candida albicans
      isolated from saliva of pediatric patients with sickle-cell anemia.
AB  - A previous study demonstrated that the amount of Candida spp. in saliva is higher
      in children with sickle-cell disease. The results from a recent study demonstrate
      its participation in the etiology of dental caries. Objective This study assessed
      caries-associated virulence (production of acid, extracellular polysaccharides,
      proteins and metabolic activity) of biofilms from Candida albicans isolated from
      saliva of patients with sickle-cell anemia in comparison to isolates obtained
      from matched healthy children. Material and Methods The isolates were previously
      obtained from 25 children (4-6 years) and their matched controls (healthy
      children). One isolate of C. albicans per children was used, totaling 25 isolates
      per group. The C. albicans biofilms were grown for five days and analyzed
      regarding the production of lactic acid, extracellular polysaccharides, proteins
      and metabolic activity. The production of lactic acid was determined by the
      enzymatic method. The concentration of extracellular polysaccharides was
      determined by the phenol-sulphuric acid method, and the concentration of the
      protein was analyzed using the QuantiPro BCA kit. The XTT reduction was used to
      verify the metabolic activity. The data were analyzed with GraphPad Prism at 5%.
      Results The Mean+/-standard deviation for acid production, extracellular
      polysaccharides, proteins and metabolic activity of isolates from sickle-cell
      group was, respectively: 7.1+/-5.0 mmol/L; 15.6+/-2.5 MUg glucose/mg biofilm;
      7,503+/-3,097 MUg/mL; A490 3.5+/-0.7. For isolates from control group the values
      obtained were: 3.5+/-3.3 mmol/L; 12.8+/-3.4 MUg glucose/mg biofilm; 4,995+/-682
      MUg/mL; A490 3.4+/-0.5. The C. albicans isolates from patients with sickle-cell
      anemia produced a significantly greater quantity of acids (p=0.025),
      polysaccharides (p=0.025) and proteins (p=0.047) compared with the isolates from
      control group. However, there was no difference in metabolic activity (XTT)
      between groups (p=0.750). Conclusion The C. albicans biofilms from patients with
      sickle-cell anemia presented a greater caries-associated virulence than isolates
      from healthy children. 

PMID- 25591018
TI  - A castor oil-containing dental luting agent: effects of cyclic loading and
      storage time on flexural strength.
AB  - Favorable results in the use of castor oil polyurethane (COP) as pulp capping,
      membrane material, sealer, mouthwash and in bone repair, associated with the fact
      that Ricinus communis is not derived from petroleum and it is abundant in Brazil,
      encourage researches in the development of luting agents. Objectives This study
      compared the flexural strength (FS) of a castor oil-containing dental luting
      agent with a weight percentage of 10% (wt%) of calcium carbonate (COP10) with
      RelyX ARC (RX) after mechanical cycling (MC) and distilled water storage.
      Material and Methods Sixty-four specimens (25x2x2 mm) were fabricated and divided
      into two groups, COP10 and RX (control). Each group was divided into 4 subgroups
      (n=8) according to the storage time, 24 hours (24 h) or 60 days (60 d), and the
      performance (MC+FS) or not (only FS) of the mechanical cycling test. The FS (10
      kN; 0.5 mm/min) and MC tests (10,000 cycles, 5 Hz, 0.5 mm/min) were carried out
      using an MTS-810 machine. The data were analyzed using ANOVA (alpha=0.05).
      Results The obtained FS (MPa) values were: COP10 24h- 19.04+/-2.41; COP10 60d-
      17.92+/-3.54; RX 24h- 75.19+/-3.43; RX 60d- 88.77+/-6.89. All the RX specimens
      submitted to MC fractured, while the values for COP10 after MC were as follows:
      COP10 24h- 17.90+/-1.87 and COP10 60d- 18.60+/-1.60. Conclusions A castor oil
      containing dental luting agent with a weight percentage of 10% (wt%) of calcium
      carbonate is resistant to mechanical cycling without decreases in flexural
      strength. However, mean COP10 showed only about 25% of the RelyX ARC mean
      flexural strength. 

PMID- 25591019
TI  - Evaluation of technical quality and periapical health of root-filled teeth by
      using cone-beam CT.
AB  - OBJECTIVE: This study aimed to assess the quality of root fillings, coronal
      restorations, complications of all root-filled teeth and their association with
      apical periodontitis (AP) detected by cone-beam computed tomography (CBCT) images
      from an adult Turkish subpopulation. MATERIAL AND METHODS: The sample for this
      study consisted of 242 patients (aging from 15 to 72 years) with 522
      endodontically treated teeth that were assessed for technical quality of the root
      canal filling and periapical status of the teeth. Additionally, the apical status
      of each root-filled tooth was assessed according to the gender, dental arch,
      tooth type and age classification, undetected canals, instrument fracture, root
      fracture, apical resorption, apical lesion, furcation lesion and type and quality
      of the coronal structure. Statistical analysis was performed using percentages
      and chi-square test. RESULTS: The success rate of the root canal treatment was of
      54.4%. The success rates of adequate and inadequate root canal treatment were not
      significantly different (p>0.05). Apical periodontitis was found in 228 (45.6%)
      teeth treated for root canals. Higher prevalence of AP was found in patients
      aging from 20 to 29 years [64 (27%) teeth] and in anterior (canines and incisors)
      teeth [97 (41%) teeth]. CONCLUSIONS: The technical quality of root canal filling
      performed by dental practitioners in a Turkish subpopulation was consistent with
      a high prevalence of AP. The probable reasons for this failure are
      multifactorial, and there may be a need for improved undergraduate education and
      postgraduate courses to improve the clinical skills of dental practitioners in
      endodontics.

PMID- 25591020
TI  - Thickness and marking quality of different occlusal contact registration strips.
AB  - OBJECTIVES: Evaluate the thickness and the marking quality of different occlusal
      contact registration strips (OCRS) and a possible correlation between them.
      MATERIAL AND METHODS: The following OCRS were selected: Accufilm II, BK20, BK21,
      BK22, BK23, BK28, and BK31. The thickness was measured in three points of the
      OCRS with an electronic measuring device (TESA), and the mean was calculated. To
      produce the marks on the strips, composite resin specimens were adapted to a
      universal testing machine (Versat 2000) with 40 kgf load cell at a speed of 1.0
      mm/min. The mark images were photographed with a stereoscopic microscope (Stemi
      SV11) and processed and analyzed by the 550-Leica Qwin analyzer. RESULTS: Values
      (MUm) found in the 1st and 2nd thickness measurements were: Accufilm II - 16.4
      and 14.2; BK20 - 10.0 and 8.1; BK21 - 9.5 and 8.0; BK22 - 9.7 and 8.7; BK23 - 9.8
      and 7.9; BK28 - 12.8 and 10.0; and BK31 - 8.4 and 8.0, respectively. The mean
      (mm2) values found in the mark areas were: Accufilm II - 0.078; BK20 - 0.035;
      BK21 - 0.045; BK22 - 0.012; BK23 - 0.022; BK28 - 0.024; and BK31 - 0.024. The
      results were submitted to the Kruskal-Wallis (p<0.05) and Pearson's correlation
      tests. CONCLUSIONS: Only in the 2nd measurement, the OCRS thickness observed was
      similar to the value indicated by the manufacturers; the Accufilm II and the BK28
      strips showed the better marks; and no correlation was found between the
      thickness and the marking area.

PMID- 25591021
TI  - Association between periodontal condition and subgingival microbiota in women
      during pregnancy: a longitudinal study.
AB  - OBJECTIVE: In this study, the gingival conditions and the quantitative detection
      for Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas
      gingivalis and Prevotella intermedia in pregnant women were determined. MATERIAL
      AND METHODS: Quantitative determinations of periodontal bacteria by using a SyBr
      green system in women during pregnancy were performed. Women at the 2nd and 3rd
      trimesters of pregnancy and non-pregnant women were included in this study. A.
      actinomycetemcomitans was observed in high numbers in women at the 2nd and 3rd
      trimesters of pregnancy with a significant difference (p<0.05). F. nucleatum and
      P. intermedia were also observed in high levels. RESULTS AND CONCLUSION: Our
      results show that pregnant women are more susceptible to gingivitis, and the
      presence of A. actinomycetemcomitans in subgingival biofilm might be taken into
      account for the treatment of periodontal disease.

PMID- 25591022
TI  - Immunolocalization of markers for bone formation during guided bone regeneration
      in osteopenic rats.
AB  - OBJECTIVE: The aim of this paper was to evaluate the repair of onlay autogenous
      bone grafts covered or not covered by an expanded polytetrafluoroethylene (e
      PTFE) membrane using immunohistochemistry in rats with induced estrogen
      deficiency. MATERIAL AND METHODS: Eighty female rats were randomly divided into
      two groups: ovariectomized (OVX) and with a simulation of the surgical procedure
      (SHAM). Each of these groups was again divided into groups with either placement
      of an autogenous bone graft alone (BG) or an autogenous bone graft associated
      with an e-PTFE membrane (BGM). Animals were euthanized on days 0, 7, 21, 45, and
      60. The specimens were subjected to immunohistochemistry for bone sialoprotein
      (BSP), osteonectin (ONC), and osteocalcin (OCC). RESULTS: All groups (OVX+BG,
      OVX+BMG, SHAM+BG, and SHAM+BMG) showed greater bone formation, observed between 7
      and 21 days, when BSP and ONC staining were more intense. At the 45-day, the bone
      graft showed direct bonding to the recipient bed in all specimens. The ONC and
      OCC showed more expressed in granulation tissue, in the membrane groups,
      independently of estrogen deficiency. CONCLUSIONS: The expression of bone forming
      markers was not negatively influenced by estrogen deficiency. However, the
      markers could be influenced by the presence of the e-PTFE membrane.

PMID- 25591025
TI  - Preventing falls.

PMID- 25591023
TI  - Radiopacity and cytotoxicity of Portland cement associated with niobium oxide
      micro and nanoparticles.
AB  - OBJECTIVE: Mineral Trioxide Aggregate (MTA) is composed of Portland Cement (PC)
      and bismuth oxide (BO). Replacing BO for niobium oxide (NbO) microparticles (Nbu)
      or nanoparticles (Nbeta) may improve radiopacity and bioactivity. The aim of this
      study was to evaluate the radiopacity and cytotoxicity of the materials: (1) PC;
      (2) White MTA; (3) PC+30% Nbu; (4) PC+30% Nbeta. MATERIAL AND METHODS: For the
      radiopacity test, specimens of the different materials were radiographed along an
      aluminum step-wedge. For cell culture assays, Saos-2 osteoblastic-cells (ATCC HTB
      85) were used. Cell viability was evaluated through MTT assay, and bioactivity
      was assessed by alkaline phosphatase activity assay. RESULTS: The results
      demonstrated higher radiopacity for MTA, followed by Nbu and Nbeta, which had
      similar values. Cell culture analysis showed that PC and PC+NbO associations
      promoted greater cell viability than MTA. CONCLUSIONS: It was concluded that the
      combination of PC+NbO is a potential alternative for composition of MTA.

PMID- 25591026
TI  - Member profile.

PMID- 25591024
TI  - Alkali production in the mouth and its relationship with certain patient's
      characteristics.
AB  - OBJECTIVES: To assess the relationships among alkali production, diet, oral
      health behaviors, and oral hygiene. METHODS: Data from 52 subjects including
      demographics, diet, and oral hygiene scores were analyzed against the level of
      arginine and urea enzymes in plaque and saliva samples. An oral habit survey was
      completed that included: use of tobacco (TB), alcohol (AH), sugary drinks (SD),
      and diet. Alkali production through arginine deiminase (ADS) and urease
      activities were measured in smooth-surface supragingival dental plaque and un
      stimulated saliva samples from all subjects. ADS and urease activities were
      measured by quantification of the ammonia generated from the incubation of plaque
      or saliva samples. Spearman correlations were used to compute all associations.
      RESULTS: Participants in the lowest SES (Socio-economic status) group had the
      habit of consuming sugary drinks the most and had the highest rate of tobacco
      use. Males consumed significantly more alcohol than females. No significant
      relationship was found between age or gender and alkali production. Higher rates
      of sugary drink consumption and tobacco use were significantly related to lower
      alkali production. CONCLUSION: The study showed a relationship between alkali
      production and oral hygiene, diet, and certain oral health behaviors. Poor oral
      hygiene was significantly associated with age, lower SES, tobacco use, and
      alcohol, and sugary drinks consumption. Clinical relevance Certain oral health
      behaviors have an impact on oral hygiene and on alkali production; it is
      important to address these factors with patients as a strategy for caries
      control.

PMID- 25591027
TI  - Rescheduling of combination hydrocodone products: problems for long-term care
      practitioners.
AB  - The Drug Enforcement Administration recently announced the final rule to
      reschedule hydrocodone combinations from schedule III of the Controlled
      Substances Act to the more restrictive schedule II category. This regulatory
      change will have broad operational implications for practitioners serving the
      health care needs of long-term care residents. Stakeholders will need to work
      collectively to identify possible efficiencies to counter some of the anticipated
      costs as well as its effect on patient care. 

PMID- 25591028
TI  - Statins for the primary prevention of cardiovascular disease in the elderly.
AB  - OBJECTIVE: The objective is to review the evidence evaluating the efficacy of
      statin therapy for primary prevention of cardiovascular (CV) disease in the
      elderly. DATA SOURCES: A literature search of MEDLINE and PubMed (1966-January
      2013) using the terms HMG-CoA reductase inhibitor, statin, primary prevention,
      elderly, and geriatrics was performed. The search was limited to clinical trials,
      meta-analyses, and subanalyses, including primary prevention patients.
      Bibliographies of selected articles were examined to identify additional clinical
      trials. STUDY SELECTION: Fourteen clinical trials, subanalyses, and meta-analyses
      were reviewed. A total of seven clinical trials and subanalyses evaluating statin
      therapy versus placebo in the elderly primary prevention patients with a primary
      endpoint of hard coronary heart disease were included. DATA EXTRACTION: Data
      collected from the clinical trials and subanalyses included number of elderly
      patients randomized, therapy, duration of follow-up, and the incidence of
      coronary events. DATA SYNTHESIS: The average annual rates of first CV event
      increases as patients age. There is strong evidence that supports the use of
      statins for secondary prevention; although primary prevention, specifically in
      the elderly, is less defined. This paper reviews the literature specifically for
      primary prevention, for which the results have shown a trend toward decreased
      first occurrence of coronary heart disease with statin therapy in elderly
      patients. CONCLUSION: Statin therapy should be considered as a primary prevention
      therapy against coronary disease for elderly patients. Evidence-based clinical
      benefits are seen in this patient population. However, clinical judgment and
      consideration of comorbidities that may impact life expectancy should be assessed
      to determine appropriateness for individual patients.

PMID- 25591029
TI  - Expanding clinical and information services to the ambulatory older adult through
      community outreach programs.
AB  - OBJECTIVE: To share successful techniques pharmacists can use to educate
      community-based older adults about health and medications. SETTING: Events
      coordinated through MCPHS University Pharmacy Outreach Program and offered at
      Massachusetts senior centers. PRACTICE DESCRIPTION: The MCPHS University Pharmacy
      Outreach Program, staffed with pharmacists, caseworkers, and pharmacy students,
      under the supervision of licensed pharmacists, provides free medication-related
      information to Massachusetts residents. Clients also receive assistance with cost
      minimizing programs and insurance benefits. Seventy percent of contacts are older
      adults. Services are provided through a toll-free number and outreach programs.
      PRACTICE INNOVATION: Focus on expanding educational health services and includes
      selecting Medicare D plans, working with support groups, providing medication
      management for diverse cultures, educating older adults on how to search for
      health information on the Internet, and discussing medication safety and
      adherence. MAIN OUTCOME MEASUREMENTS: Participant and pharmacy student knowledge
      assessed utilizing survey tools. Additional measurements include savings for
      Medicare beneficiaries and improvements in medication management. RESULTS:
      Observed results of the Pharmacy Outreach Program include decreased out-of-pocket
      costs for Medicare beneficiaries, improved medication adherence resulting in
      reduction of glycated hemoglobin and blood pressure, identifying and recommending
      medication treatment changes to reduce patient fall risk, and increased
      confidence in locating Web-based health information. Pharmacy students
      demonstrated increased knowledge of and ability to communicate Medicare benefits.
      CONCLUSION: Outreach programs can improve older adults' understanding about their
      health and medications. Pharmacists can increase visibility in the community by
      engaging in effective outreach programs.

PMID- 25591030
TI  - Treating recurrent postmenopausal vasomotor symptoms in a patient with a positive
      family history for breast cancer.
AB  - OBJECTIVE: To report a case of recurrent hot flashes unresponsive to gabapentin
      in a postmenopausal patient with a positive family history of breast cancer. CASE
      SUMMARY: A 69-year-old Caucasian female experienced a recurrence of debilitating
      hot flashes for the past eight months. More recently, she failed a two-month
      trial of gabapentin 600 mg by mouth at bedtime after she previously received
      effective hormone replacement therapy (HRT) seven years ago with near-complete
      resolution of her symptoms. The patient had a sister and a niece who developed
      breast cancer in their 40s. DISCUSSION: The treatment of postmenopausal hot
      flashes in a patient with a positive family history of breast cancer represents a
      clinical challenge for many clinicians. This case is an example in which
      gabapentin was ineffective in the treatment of severe hot flashes in a
      postmenopausal woman. The risks and benefits of HRT compared with nonhormonal
      alternatives were assessed. CONCLUSION: In this case, a two-month trial of
      gabapentin 600 mg/day failed to demonstrate efficacy in reducing the severity,
      frequency, and duration of hot flashes. Controlled trials are necessary to
      evaluate the safety and efficacy of other therapeutic alternatives.

PMID- 25591031
TI  - Evaluation of pharmacy resident and student recommendations made before and after
      home-based primary care patient visits.
AB  - OBJECTIVE: To compare the types of recommendations documented in pharmacy
      resident and student home-visit notes with those made in the electronic medical
      record-based drug regimen review (DRR) notes. SETTING: San Francisco Veterans
      Affairs Medical Center (SFVAMC), San Francisco, California. PRACTICE DESCRIPTION:
      The SFVAMC Home-Based Primary Care (HBPC) program provides primary care services
      through an interdisciplinary team. The pharmacist performs a DRR-a federally
      required, quarterly retrospective review of the medications for each patient
      enrolled in the HBPC program and acts as a preceptor for pharmacy residents and
      students helping to provide patient care. PRACTICE INNOVATION: Starting in 2008,
      residents and students began making home visits with the HBPC primary care
      providers. Activities and recommendations were documented in a home visit
      clinical note. MAIN OUTCOME MEASURES: Number and types of recommendations
      documented during the DRR and in the home visit notes as well as the clinical
      change in disease states based on the accepted recommendations. RESULTS: Ninety
      three recommendations were accepted: 27 DRR recommendations and 66 home visit
      recommendations from August 1, 2008, to July 31, 2009. The most commonly accepted
      DRR recommendations were to evaluate response to therapy (29%) and home visit
      recommendations to document medications not listed in the medication profile
      (26%). Clinical change in disease state based on the majority of the accepted
      recommendations remained unchanged for both DRR and home visit recommendations.
      CONCLUSION: Home visits by pharmacy residents and students resulted in a greater
      number and different type of recommendations documented in their home visit notes
      compared with those in the DRR notes.

PMID- 25591032
TI  - What do the 2014 midterm election results mean for ASCP?

PMID- 25591033
TI  - Toward ultraflat surface morphologies during focused electron beam induced
      nanosynthesis: disruption origins and compensation.
AB  - Emerging applications for nanoscale materials demand precise deposit shape
      retention from design to deposition. This study investigates the effects that
      disrupt high-fidelity shapes during focused electron beam induced nanosynthesis.
      It is shown that process parameters, patterning strategies and deposit topography
      can impose lateral precursor coverage gradients during growth resulting in
      unwanted topographic artifacts. The study classifies the evolving surface shapes
      into four general types and explains the formation and transition from a
      fundamental point of view. Continuum model calculations and simulations expand
      the experimental results to provide a comprehensive insight into understand the
      disruption mechanism. The findings demonstrate that the well-established concept
      of growth regimes has to be expanded by its lateral gradients as they strongly
      influence final shape fidelities. Finally, the study is complemented by a
      compensation strategy that improves the edge fidelity on the lower nanoscale to
      further push this technique toward the intrinsic limitations. 

PMID- 25591034
TI  - Percutaneous clamping of spiral and oblique fractures of the tibial shaft: a safe
      and effective reduction aid during intramedullary nailing.
AB  - The reduction of tibial shaft fractures during intramedullary nailing is
      important if limb alignment is to be restored and successful clinical outcomes
      are expected. We have used a percutaneously applied (or open) clamp or clamps to
      achieve and maintain reduction during nailing of all amendable tibial shaft
      fractures. In this article, we describe the technique and preliminary results
      comparing closed, simple spiral and oblique tibial shaft fractures (OTA 42-A1 and
      A2) managed with percutaneous clamp-assisted nailing (CAN) versus nailing using
      manual reduction (MRN) held by the surgical team. In the MRN group, there were an
      increased fracture gap (P = 0.04) and trends toward malalignment (P = 0.07) and
      healing time (P = 0.06) compared with the CAN group. There were also trends in
      clinical; no wound complications occurred in either group. We have found that
      percutaneous CAN of closed, simple spiral and oblique tibial shaft fractures
      seems safe and allows for early predictable union with reproducible alignment
      compared with nailing using MRN. 

PMID- 25591035
TI  - A Biomechanical Study of Posteromedial Tibial Plateau Fracture Stability: Do They
      All Require Fixation?
AB  - OBJECTIVES: Although the posteromedial fragment in tibial plateau fractures is
      often considered unstable, biomechanical evidence supporting this view is
      lacking. We aimed to evaluate the stability of the fragment in a cadaver model.
      Our hypothesis was that under the expected small axial force during
      rehabilitation and the combined effects of this force with shear force, internal
      rotation torque, and varus moment, the most common posteromedial tibial fragment
      morphology could maintain stability in early flexion. METHODS: Axial compression
      force alone or combined with posterior shear, internal rotation torque, or varus
      moment was applied to the femurs of 5 fresh cadaveric knees. A Tekscan pressure
      mapping system was used to measure pressure and contact area between the femoral
      condyles, meniscus, and tibial plateau. A Microscribe 3D digitizer was used to
      define the 3-dimensional positions of the femur and tibia. A 10-mm and then a 20
      mm osteotomy was created with a saw at an angle of 30 degrees in the axial plane
      with respect to the tangent of the posterior tibial plateau and 75 degrees in the
      sagittal plane, representing a typical posteromedial fracture fragment. At each
      flexion angle (15, 30, 60, 90, and 120 degrees) and loading condition (axial
      compression only, compression with shear force, torque, and varus moment), distal
      displacement of the medial femoral condyle and the tibial fracture fragments was
      determined. RESULTS: For the 10-mm fragment, medial femoral condyle displacement
      was little affected up to approximately 30-degree flexion, after which it
      increased. For the 20-mm fragment, there was progressive medial femoral condyle
      displacement with increasing flexion from baseline. However, for the 10- and 20
      mm fragments themselves, displacements were noted at every flexion angle,
      starting at 1.7 mm inferior displacement with 15 degrees of flexion and internal
      rotation torque and up to 10.2 mm displacement with 90 degrees of flexion and
      varus bending moment. CONCLUSIONS: In this cadaveric model of a posteromedial
      tibial plateau fracture, both fracture fragments studied displaced with knee
      flexion, even at low flexion angles. Although such fragments may initially seem
      nondisplaced after injury, posteromedial fragments similar to these tested are
      likely to displace during knee range of motion exercises in non-weight-bearing
      conditions.

PMID- 25591036
TI  - Volar subluxation of the ulnar head in dorsal translation deformities of distal
      radius fractures: an in vitro biomechanical study.
AB  - OBJECTIVES: To quantify the effects of dorsal translation deformities of the
      distal radius with and without dorsal angulation on volar displacement of the
      ulnar head during simulated active forearm rotation, both with the triangular
      fibrocartilage complex (TFCC) intact and sectioned conditions. METHODS: Eight
      fresh-frozen cadaveric upper extremities were mounted in an active forearm motion
      simulator, and distal radial deformities of 0, 5, and 10 mm of dorsal translation
      with 0, 10, 20, and 30 degrees of dorsal angulation were simulated. Volar
      displacement of the ulnar head at the distal radioulnar joint as a result of each
      distal radial deformity was quantified during simulated active supination. The
      data were collected with the TFCC intact and after sectioning the TFCC at its
      ulnar insertion. RESULTS: Increasing isolated dorsal translation deformities
      increased volar displacement of the ulnar head when the TFCC was intact (P <
      0.001). Increasing dorsal translation combined with dorsal angulation increased
      volar displacement of the ulnar head compared with isolated dorsal angulation
      deformities (P < 0.001). Sectioning the TFCC increased the volar displacement of
      the ulnar head caused by each distal radial deformity (P = 0.001). CONCLUSIONS:
      These results emphasize the clinical importance of evaluating the magnitude of
      both dorsal translation and dorsal angulation when managing displaced distal
      radius fractures and malunions.

PMID- 25591037
TI  - Passively scattered proton beam entrance dosimetry with a plastic scintillation
      detector.
AB  - We tested the feasibility of using plastic scintillation detectors (PSDs) for
      proton entrance dosimetry. A PSD built with BCF-12 scintillating fiber was used
      to measure the absolute entrance dose of a passively scattered proton beam for
      energies ranging from 140 to 250 MeV, and for a range of spread out Bragg peak
      (SOBP) widths at two energies, to quantify the effect of ionization quenching on
      the response of the detector and to determine the necessity of Cerenkov radiation
      correction in proton beams. The overall accuracy and precision of the PSD was
      evaluated by measuring lateral beam profiles and comparing the results with
      profiles measured using film. The PSD under-responded owing to ionization
      quenching, exhibiting approximately a 7% loss of signal at the highest energy
      studied (250 MeV) and a 10% loss of signal at the lowest energy studied (140
      MeV). For a given nominal energy, varying the SOBP width did not significantly
      alter the response of the PSD. Cerenkov radiation contributed negligibly to the
      PSD signal and can be safely ignored without introducing more than 1% error in
      the measured dose. Profiles measured with the PSD and film agreed to within the
      uncertainty of the detector, demonstrating good relative accuracy. Although
      correction factors were necessary to account for ionization quenching, the
      magnitude of the correction varied minimally over a broad range of energies; PSDs
      therefore represent a practical detector for proton entrance dosimetry. 

PMID- 25591038
TI  - Light-responsive iron(III)-polysaccharide coordination hydrogels for controlled
      delivery.
AB  - Visible-light responsive gels were prepared from two plant-origin polyuronic
      acids (PUAs), alginate and pectate, coordinated to Fe(III) ions. Comparative
      quantitative studies of the photochemistry of these systems revealed unexpected
      differences in the photoreactivity of the materials, depending on the
      polysaccharide and its composition. The roles that different functional groups
      play on the photochemistry of these biomolecules were also examined. Mannuronic
      rich alginates were more photoreactive than guluronic acid-rich alginate and than
      pectate. The microstructure of alginates with different mannuronate-to-guluronate
      ratios changed with polysaccharide composition. This influenced the gel
      morphology and the photoreactivity. Coordination hydrogel beads were prepared
      from both Fe-alginate and Fe-pectate. The beads were stable carriers of molecules
      as diverse as the dye Congo Red, the vitamin folic acid, and the antibiotic
      chloramphenicol. The photoreactivity of the hydrogel beads mirrored the
      photoreactivity of the polysaccharides in solution, where beads prepared with
      alginate released their cargo faster than beads prepared with pectate. These
      results indicate important structure-function relationships in these systems and
      create guidelines for the design of biocompatible polysaccharide-based materials
      where photoreactivity and controlled release can be tuned on the basis of the
      type of polysaccharide used and the metal coordination environment. 

PMID- 25591039
TI  - Asperlones A and B, dinaphthalenone derivatives from a mangrove endophytic fungus
      Aspergillus sp. 16-5C.
AB  - Racemic dinaphthalenone derivatives, (+/-)-asperlone A (1) and (+/-)-asperlone B
      (2), and two new azaphilones, 6'-hydroxy-(R)-mitorubrinic acid (3) and
      purpurquinone D (4), along with four known compounds, (-)-mitorubrinic acid (5),
      (-)-mitorubrin (6), purpurquinone A (7) and orsellinic acid (8), were isolated
      from the cultures of Aspergillus sp. 16-5C. The structures were elucidated using
      comprehensive spectroscopic methods, including 1D and 2D NMR spectra and the
      structures of 1 further confirmed by single-crystal X-ray diffraction analysis,
      while the absolute configuration of 3 and 4 were determined by comparing their
      optical rotation and CD with those of the literature, respectively. Compounds 1,
      2 and 6 exhibited potent inhibitory effects against Mycobacterium tuberculosis
      protein tyrosine phosphatase B (MptpB) with IC50 values of 4.24 +/- 0.41, 4.32 +/
      0.60 and 3.99 +/- 0.34 MUM, respectively. 

PMID- 25591040
TI  - Combination of trabectedin and gemcitabine for advanced soft tissue sarcomas:
      results of a phase I dose escalating trial of the German Interdisciplinary
      Sarcoma Group (GISG).
AB  - BACKGROUND: Evaluation of the potential efficacy and safety of combination
      therapies for advanced soft tissue sarcomas (STS) has increased substantially
      after approval of trabectedin and pazopanib. Trabectedin's introduction in Europe
      in 2007 depended mainly on its activity in so-called L-sarcomas (liposarcoma and
      leiomyosarcoma); combination of trabectedin with other chemotherapies used in STS
      seems of particular interest. METHODS: We initiated within the German
      Interdisciplinary Sarcoma Group (GISG) a phase I dose escalating trial evaluating
      the combination of trabectedin and gemcitabine in patients with advanced and/or
      metastatic L-sarcomas (GISG-02; ClinicalTrials.gov NCT01426633). Patients were
      treated with increasing doses of trabectedin and gemcitabine. The primary
      endpoint was to determine the maximum tolerated dose. RESULTS: Five patients were
      included in the study. Two patients were treated on dose level 1 comprising
      trabectedin 0.9 mg/m2 on day 1 and gemcitabine 700 mg/m2 on days 1 + 8, every 3
      weeks. Due to dose-limiting toxicity (DLT) in both patients (elevated
      transaminases and thrombocytopenia), an additional three patients were treated on
      dose level -1 with trabectedin 0.7 mg/m2 plus gemcitabine 700 mg/m2. Of these
      three patients, two demonstrated another DLT; therefore, the trial was stopped
      and none of the dose levels could be recommended for phase II testing.
      CONCLUSION: The GISG-02 phase I study was stopped with the conclusion that the
      combination of gemcitabine and trabectedin is generally not recommended for the
      treatment of patients with advanced and/or metastatic leiomyosarcoma or
      liposarcoma. Also, this phase I study strongly supports the necessity for careful
      evaluation of combination therapies.

PMID- 25591043
TI  - Impaired autophagosome clearance contributes to local anesthetic bupivacaine
      induced myotoxicity in mouse myoblasts.
AB  - BACKGROUND: The current study examined the role(s) of autophagy in myotoxicity
      induced by bupivacaine in mouse myoblast C2c12 cells. METHODS: C2c12 cells were
      treated with bupivacaine. Myotoxicity was evaluated by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay (n = 3 to 30), live/dead assay (n = 3
      to 4), and morphological alterations (n = 3). Autophagosome formation was
      reflected by microtubule-associated protein light chain 3 conversion (n = 4 to
      12) and light chain 3 punctation (n = 4 to 5). Autophagosome clearance was
      evaluated by p62 protein level (n = 4) and autolysosomes generation (n = 3).
      RESULTS: Bupivacaine induced significant cell damage. Notably, there was a
      significant increase in autophagosome generation as evidenced by light chain 3
      puncta formation (72.7 +/- 6.9 vs. 2.1 +/- 1.2) and light chain 3 conversion
      (2.16 +/- 0.15 vs. 0.33 +/- 0.04) in bupivacaine-treated cells. Bupivacaine
      inactivated the protein kinase B/mammalian target of rapamycin/p70 ribosomal
      protein S6 kinase signaling. However, cellular levels of p62 protein were
      significantly increased upon bupivacaine treatment (1.29 +/- 0.15 vs. 1.00 +/-
      0.15), suggesting that the drug impaired autophagosome clearance. Further
      examination revealed that bupivacaine interrupted autophagosome-lysosome fusion
      (10.87% +/- 1.48% vs. 32.94% +/- 4.22%). Administration of rapamycin increased
      autophagosome clearance and, most importantly, improved the survival in
      bupivacaine-treated cells. However, knockdown of autophagy-related protein 5
      (atg5) exacerbated bupivacaine-induced impairment of autophagosome clearance and
      myotoxicity. CONCLUSIONS: The data suggest that autophagosome formation was
      induced as a stress response mechanism after bupivacaine challenge; however,
      autophagosome clearance was impaired due to inadequate autophagosome-lysosome
      fusion. Therefore, impairment of autophagosome clearance appears to be a novel
      mechanism underlying bupivacaine-induced myotoxicity.

PMID- 25591041
TI  - [I Guidelines of heart failure and heart transplantation in the fetus, in
      children and adults with congenital cardiopathy, The Brazilian Society of
      Cardiology].

PMID- 25591042
TI  - Synergistic Inhibition of beta2-adrenergic Receptor-mediated Alveolar Epithelial
      Fluid Transport by Interleukin-8 and Transforming Growth Factor-beta.
AB  - BACKGROUND: Patients with acute respiratory distress syndrome who retain maximal
      alveolar fluid clearance (AFC) have better clinical outcomes. The release of
      endogenous catecholamines associated with shock or the administration of beta2
      adrenergic receptor (beta2AR) agonists enhances AFC via a 3'-5'-cyclic adenosine
      monophosphate-dependent mechanism. The authors have previously reported that
      transforming growth factor-beta1 (TGF-beta1) and interleukin-8 (IL-8), two major
      mediators of alveolar inflammation associated with the early phase of acute
      respiratory distress syndrome, inhibit AFC upregulation by beta2AR agonists via a
      phosphoinositol-3-kinase (PI3K)-dependent mechanism. However, whether TGF-beta1
      and IL-8 cause an additive or synergistic inhibition of AFC is unclear. Thus, the
      central hypothesis of the study was to determine whether they synergistically
      inhibit the beta2AR-stimulated AFC by activating two different isoforms of PI3K.
      METHODS: The effects of TGF-beta1 or IL-8 on beta2AR agonist-stimulated net
      alveolar fluid transport were studied using short-circuit current studies.
      Molecular pathways of inhibition were confirmed by pharmacologic inhibitors and
      Western blotting of p-Akt, G-protein-coupled receptor kinase 2, protein kinase C
      zeta, and phospho-beta2AR. Finally, our observations were confirmed by an in vivo
      model of AFC. RESULTS: Combined exposure to TGF-beta1 and IL-8/cytokine-induced
      neutrophil chemoattractant-1 caused synergistic inhibition of beta2AR agonist
      stimulated vectorial Cl across alveolar epithelial type II cells (n = 12 in each
      group). This effect was explained by activation of different isoforms of PI3K by
      TGF-beta1 and IL-8/cytokine-induced neutrophil chemoattractant-1 (n = 12 in each
      group). Furthermore, the inhibitory effect of TGF-beta1 on 3'-5'-cyclic adenosine
      monophosphate-stimulated alveolar epithelial fluid transport required the
      presence of IL-8/cytokine-induced neutrophil chemoattractant-1 (n = 12 in each
      group). Inhibition of cytokine-induced neutrophil chemoattractant-1 prevented TGF
      beta1-mediated heterologous beta2AR downregulation and restored physiologic
      beta2AR agonist-stimulated AFC in rats (n = 6 in each group). CONCLUSIONS: TGF
      beta1 and IL-8 have a synergistic inhibitory effect on beta2AR-mediated
      stimulation of pulmonary edema removal by the alveolar epithelium. This result
      may, in part, explain why a large proportion of the patients with acute
      respiratory distress syndrome have impaired AFC.

PMID- 25591044
TI  - Sleep problems and cognitive behavior therapy in pediatric obsessive-compulsive
      disorder have bidirectional effects.
AB  - OBJECTIVES: To investigate the presence of sleep problems and their reaction to
      CBT in pediatric obsessive compulsive disorder (OCD). Moreover, we investigated
      whether sleep problems predict the outcome of CBT on OCD-symptoms. METHODS: 269
      children and adolescents, age 7-17 years, with DSM-IV primary OCD that took part
      in the first step of a stepwise treatment trial, were assessed with regard to
      both individual sleep problems and a sleep composite score (SCS) using the Child
      Behavior Checklist (CBCL). Their OCD symptoms were rated using the Children Yale
      Brown Obsessive Compulsive Scale (CY-BOCS). RESULTS: We found elevated symptoms
      of sleep deprivation and nightmares before treatment. However most sleep problems
      (e.g. nightmares (p=.03), too little sleep (p<.001), trouble sleeping (p<.001)
      and parasomnias p=.03)) as well as being over-tired (p<.001) reduced during CBT
      treatment. Co-morbidities had no effect on the reduction of SCS. Moreover,
      elevated levels of sleep problems using the SCS (p<.001), as well as any sleep
      problem at baseline (p<.001) predicted less effect of CBT on the OCD symptoms.
      CONCLUSION: Sleep problems in paediatric OCD are frequent and interfere with
      treatment outcome. They need to be assessed using better methods in future
      trials. Moreover, lack of resolution of sleep problems need to be recognized and
      treated as it seems probable that continued sleep problems may have a negative
      impact on CBT efficacy.

PMID- 25591045
TI  - Serum docosahexaenoic acid (DHA) is inversely associated with anxiety disorders
      in early pregnancy.
AB  - Little is known about the association between polyunsaturated fatty acids (PUFAs)
      and anxiety disorders during pregnancy. We evaluated this association at the
      first pregnancy trimester in 228 women. The study endpoint was the diagnosis of
      any anxiety disorder assessed by the Mini International Neuropsychiatric
      Interview. The independent variables were the serum concentrations of total n-3
      and fractions (18:2, 20:5, 22:5, 22:6), total n-6 and fractions (18:2, 18:3,
      20:2, 20:3, 20:4, 22:4, 22:5) and the n-6/n-3 ratio PUFAs. The prevalence of any
      anxiety disorders was 25%. The first tertile of the docosahexaenoic acid (DHA,
      22:6 n-3) distribution represented 1.95 (95% CI: 1.00-3.77) higher chance of
      having an anxiety disorder diagnosis, compared to those in the second and third
      tertiles after adjusting the analyses for parity, family income, early pregnancy
      BMI and gestational age at the blood sampling. Serum concentrations of DHA were
      inversely associated with the occurrence of early pregnancy anxiety disorders. 

PMID- 25591046
TI  - Excoriation disorder: impulsivity and its clinical associations.
AB  - Excoriation disorder is the repetitive scratching or picking of skin that leads
      to physical damage, distress, and functional impairment. Skin picking has been
      associated with impulsivity and problems with inhibition. We hypothesized that
      problems in these areas could be disease severity markers. We recruited 73 adults
      meeting DSM-5 criteria for excoriation disorder, and 50 adult controls. Those
      with excoriation disorder were categorized as either "high impulsive" (HI) or
      "low impulsive" (LI) using either a neurocognitive task of motor impulsivity
      (Stop Signal Task) or the Barratt Impulsiveness Scale's (BIS-11) motor
      impulsivity subscale. The HI subjects, based on the BIS-11, showed higher urges
      scores, anxiety, and depressive symptoms. These data suggest that impulsivity may
      reflect a specific clinical presentation among those with excoriation disorder,
      but the clinical characteristics differ depending upon the impulsivity measure
      used. Agreement on how to measure various domains of impulsivity may be important
      in better understanding the disorder psychopathology and so improve future
      treatments. 

PMID- 25591047
TI  - Mercury in little brown bat (Myotis lucifugus) maternity colonies and its
      correlation with freshwater acidity in Nova Scotia, Canada.
AB  - Insectivorous little brown bats are exposed to elevated concentrations of mercury
      (Hg) through their preference for aquatic-based prey. Here we investigated
      spatial patterns of total Hg (THg) in fur from 10 little brown bat maternity
      colonies across Nova Scotia, and assessed relationships with the acidity of
      nearby lakes and rivers. Total Hg concentrations were measured in fur samples
      from 149 adult female little brown bats. Values showed significant variation
      among colonies (mean range 3.76-27.38 MUg/g, dry weight), and 48% of individuals
      had Hg concentrations in excess of the 10 MUg/g threshold associated with
      neurochemical changes in Chiroptera conspecifics (n = 26) from Virginia. Average
      surface water acidity parameters (pH and acid neutralization capacity) within an
      8 km radius of each maternity roost showed strong negative associations with
      average colony fur THg concentrations. This suggests that freshwater acidity in
      foraging grounds explains much of the variation in average fur THg concentrations
      in little brown bat colonies. These findings highlight the significant role that
      water quality may have on Hg bioaccumulation within terrestrial species that feed
      on aquatic prey.

PMID- 25591048
TI  - Indicators of hypertriglyceridemia from anthropometric measures based on data
      mining.
AB  - BACKGROUND: The best indicator for the prediction of hypertriglyceridemia derived
      from anthropometric measures of body shape remains a matter of debate. The
      objectives are to determine the strongest predictor of hypertriglyceridemia from
      anthropometric measures and to investigate whether a combination of measures can
      improve the prediction accuracy compared with individual measures. METHODS: A
      total of 5517 subjects aged 20-90 years participated in this study. The numbers
      of normal and hypertriglyceridemia subjects were 3022 and 653 females,
      respectively, and 1306 and 536 males, respectively. We evaluated 33
      anthropometric measures for the prediction of hypertriglyceridemia using
      statistical analysis and data mining. RESULTS: In the 20-90-year-old groups, age
      in women was the variable that exhibited the highest predictive power; however,
      this was not the case in men in all age groups. Of the anthropometric measures,
      the waist-to-height ratio (WHtR) was the best predictor of hypertriglyceridemia
      in women. In men, the rib-to-forehead circumference ratio (RFcR) was the
      strongest indicator. The use of a combination of measures provides better
      predictive power compared with individual measures in both women and men.
      However, in the subgroups of ages 20-50 and 51-90 years, the strongest indicators
      for hypertriglyceridemia were rib circumference in the 20-50-year-old group and
      WHtR in the 51-90-year-old group in women and RFcR in the 20-50-year-old group
      and BMI in the 51-90-year-old group in men. CONCLUSIONS: Our results demonstrated
      that the best predictor of hypertriglyceridemia may differ according to gender
      and age.

PMID- 25591049
TI  - The poro-viscoelastic properties of trabecular bone: a micro computed tomography
      based finite element study.
AB  - Bone is a porous structure with a solid phase that contains hydroxyapatite and
      collagen. Due to its composition, bone is often represented either as a
      poroelastic or as a viscoelastic material; however, the poro-viscoelastic
      formulation that allows integrating the effect of both the fluid flow and the
      collagen on the mechanical response of the tissue, has not been applied yet. The
      objective of this study was to develop a micro computed tomography (uCT)-based
      finite element (FE) model of trabecular bone that includes both the poroelastic
      and the viscoelastic nature of the tissue. Cubes of trabecular bone (N=25) from
      human distal tibia were scanned with uCT and stress relaxation experiments were
      conducted. The uCT images were the basis for sample specific FE models, and the
      stress relaxation experiments were simulated applying a poro-viscoelastic
      formulation. The model considers two scales of the tissue: the intertrabecular
      pore and the lacunar-canalicular pore scales. Independent viscoelastic and
      poroelastic models were also developed to determine their contribution to the
      poro-viscoelastic model. All the experiments exhibited a similar relaxation
      trend. The average reaction force before relaxation was 9.28 * 10(2)N (SD +/-
      5.11 * 10(2)N), and after relaxation was 4.69 * 10(2)N (SD +/- 2.88 * 10(2)N).
      The slope of the regression line between the force before and after relaxation
      was 1.92 (R(2)=0.96). The poro-viscoelastic models captured 49% of the
      variability of the experimental data before relaxation and 33% after relaxation.
      The relaxation predicted with viscoelastic models was similar to the poro
      viscoelastic ones; however, the poroelastic formulation underestimated the
      reaction force before relaxation. These data suggest that the contribution of
      viscoelasticity (fluid flow-independent mechanism) to the mechanical response of
      the tissue is significantly greater than the contribution of the poroelasticity
      (fluid flow-dependent mechanism).

PMID- 25591050
TI  - One step closer to targeting RAS.

PMID- 25591051
TI  - On the self-assembly of TiOx into 1D NP network nanostructures.
AB  - Here, we report for the first time a 'ligand free' method of designing 1D TiOx
      supramolecular network materials, which starts from Ti bare metal powder. Each
      TiOx oxidation step has been carefully investigated with different analytical
      techniques, including high resolution transmission electron microscopy/high
      resolution scanning electron microscopy (HRTEM/HRSEM), x-ray photoelectron
      spectroscopy (XPS), Raman spectroscopy and superconducting quantum interference
      device (SQUID) measurements. The self-assembly of TiOx nanoparticles (NPs) into
      1D supramolecular nanoparticle networks is induced by the formation of mixed
      valent Ti(II,III) species. The synthesis starts with etching a bare Ti surface,
      followed by a continuous oxidation of TiOx clusters and NPs, and it finally ends
      with the self-assembly into rigid 1D NPs chains. Today, such self-assembled 1D NP
      TiOx network materials are bridging the gap between the nanoscale and the
      macroscopic material world and will further provide interesting research
      opportunities. 

PMID- 25591052
TI  - Analyzing B-vitamins in Human Milk: Methodological Approaches.
AB  - According to the World Health Organization (WHO), infants should be exclusively
      breastfed for the first six months of life. However, there is insufficient
      information about the concentration of nutrients in human milk. For some
      nutrients, including B-vitamins, maternal intake affects their concentration in
      human milk but the extent to which inadequate maternal diets affect milk B
      vitamin content is poorly documented. Little is known about infant requirements
      for B-vitamins; recommendations are generally set as Adequate Intakes (AI)
      calculated on the basis of the mean volume of milk (0.78 L/day) consumed by
      infants exclusively fed with human milk from well-nourished mothers during the
      first six months, and the concentration of each vitamin in milk based on reported
      values. Methods used for analyzing B-vitamins, commonly microbiological,
      radioisotope dilution or more recently chromatographic, coupled with UV,
      fluorometric and MS detection, have rarely been validated for the complex human
      milk matrix. Thus the validity, accuracy, and sensitivity of analytical methods
      is important for understanding infant requirements for these nutrients, the
      maternal intakes needed to support adequate concentrations in breast milk. This
      review summarizes current knowledge on methods used for analyzing the B-vitamins
      thiamin, riboflavin, niacin, vitamin B-6 and pantothenic acid, vitamin B-12,
      folate, biotin, and choline in human milk, their chemical and physical
      properties, the different forms and changes in concentration during lactation,
      and the effects of deficiency on the infant. 

PMID- 25591053
TI  - Effects of therapeutic Tai Chi on balance, gait, and quality of life in chronic
      stroke patients.
AB  - The aim of this study was to analyze the effects of therapeutic Tai Chi on
      balance, gait, and quality of life in chronic stroke patients. Twenty-two
      inpatients diagnosed with stroke were divided randomly into two groups: one
      treated with both general physical therapy and Tai Chi exercise (11 patients) and
      one treated with only general physical therapy (11 patients). Therapeutic Tai Chi
      included 10 different movements and was performed for 60 min, twice per week, for
      6 weeks. Pretest and post-test measurements were recorded for sway length and
      sway velocity using Gaitview, the functional reach test, the dynamic gait index,
      the 10-m walking test, the timed up-and-go test, and SF-36 survey. Both the Tai
      Chi group and the control group showed a significant improvement in sway length
      and sway velocity, and the Tai Chi group showed greater improvement than the
      control group in degree of variation. In addition, only the Tai Chi group showed
      a significant result for functional reach test, the dynamic gait index, the 10-m
      walking test, the timed up-and-go test, and the Tai Chi group improved. In the
      quality of life, the therapeutic Tai Chi group showed a significant improvement
      in five items (physical function, pain, vitality, general health, mental health)
      among eight items in SF-36. This study confirmed that therapeutic Tai Chi
      influences the balance, gait, and life quality of stroke patients. Therefore,
      therapeutic Tai Chi can be used as an effective exercise in combination with
      general physical therapy to improve the balance, gait, and quality of life in
      stroke patients. 

PMID- 25591054
TI  - Robotic tilt table reduces the occurrence of orthostatic hypotension over time in
      vegetative states.
AB  - The aim of this study is to evaluate the effects of verticalization with or
      without combined movement of the lower limbs in patients in a vegetative state or
      a minimally conscious state. In particular, we aimed to study whether, in the
      group with combined movement, there was better tolerance to verticalization. This
      was a randomized trial conducted in a neurorehabilitation hospital. Twelve
      patients with vegetative state and minimally conscious state 3-18 months after
      acute acquired brain injuries were included. Patients were randomized into A and
      B treatment groups. Study group A underwent verticalization with a tilt table at
      65 degrees  and movimentation of the lower limbs with a robotic system for 30 min
      three times a week for 24 sessions. Control group B underwent the same
      rehabilitation treatment, with a robotic verticalization system, but an inactive
      lower-limb movement system. Systolic and diastolic blood pressure and heart rate
      were determined. Robotic movement of the lower limbs can reduce the occurrence of
      orthostatic hypotension in hemodynamically unstable patients. Despite the small
      number of patients involved (only eight patients completed the trial), our
      results indicate that blood pressures and heart rate can be stabilized better
      (with) by treatment with passive leg movements in hemodynamically unstable
      patients. 

PMID- 25591056
TI  - Longevity through DNA damage tolerance.

PMID- 25591057
TI  - Find me the evidence: connecting the practitioner with the evidence on
      bereavement care.
AB  - Care practices change as knowledge emerges and research findings challenge
      current approaches. Access to evidence has challenges. Bereavement care is
      diverse: practitioners often work alone or in small teams, terminology can be
      diffuse, and practitioners may not have time and skills for effective search
      strategies. CareSearch, an online palliative care resource, is hosting the
      Bereavement Search Filter, a validated search strategy to facilitate access to
      bereavement care evidence. The service connects practitioners to global best
      practice evidence; it is free and trustworthy. This article outlines the
      development of the Medline Bereavement Search Filter, translating it for PubMed
      and deploying it online. 

PMID- 25591058
TI  - Role of catecholamines in acute hypertensive response: subarachnoid hemorrhage
      versus spontaneous intracerebral hemorrhage.
AB  - BACKGROUND AND OBJECTIVE: Acute hypertensive response, defined as systolic blood
      pressure (SBP) 140 mmHg or more within 24 h of onset, is frequently observed in
      hemorrhagic stroke patients. Although catecholamine surge is pivotal in its
      pathogenesis, few studies have evaluated the relationship between admission SBP
      and plasma catecholamine levels. PATIENTS AND METHODS: A prospective
      observational study was carried out to investigate potential differences in the
      acute hypertensive reaction between subarachnoid hemorrhage (SAH) and spontaneous
      intracerebral hemorrhage (SICH) by analyzing 200 SAH and 200 SICH patients. In
      each category, patients were quadrichotomized on the basis of their SBPs in
      emergency department: less than 140 mmHg, 140-184 mmHg, 185-219 mmHg, and 220
      mmHg or more. The plasma catecholamine levels were compared among the four
      groups. Furthermore, multivariate regression analyses were carried out to
      identify variables correlated with hypertensive emergency (SBP>=185 mmHg).
      RESULTS: In SAH patients, there was a proportional increase in norepinephrine
      levels relative to the graded SBPs, and norepinephrine levels in the 220 mmHg or
      more group were significantly higher than those in the less than 140 mmHg group
      (1596+/-264 vs. 853+/-124 pg/ml, P=0.03). By contrast, no proportional increase
      in norepinephrine levels to the graded SBPs was observed in SICH patients.
      Multivariate regression analyses showed that the initial Glasgow Coma Scale
      scores of 8 or less (odds ratio 2.251, 95% confidence interval 1.002-5.117) and
      plasma norepinephrine levels (odds ratio 1.002, 95% confidence interval 1.001
      1.003) were correlated with hypertensive emergency in SAH patients. By contrast,
      none of the variables evaluated were correlated with hypertensive emergency in
      SICH patients. CONCLUSION: An acute hypertensive response may be more complex,
      multifactorial, and less catecholamine dependent in SICH patients compared with
      SAH patients.

PMID- 25591059
TI  - Identifying masked uncontrolled hypertension in the community pharmacy setting.
AB  - Masked uncontrolled hypertension (MUCH) is associated with an increased
      cardiovascular risk. This condition is frequent in the community pharmacy (i.e.,
      CP-MUCH), but there is no evidence on the factors associated with its presence in
      that setting. The aim of this analysis was to explore these factors. A sample of
      98 treated hypertensive patients from the MEPAFAR study, with normal community
      pharmacy blood pressure (CPBP <135/85 mmHg), were analyzed. Blood pressure (BP)
      was also measured at home (4 days) and monitored for 24 h. CP-MUCH was identified
      when either ambulatory (daytime) or home BP averages were equal to or higher than
      135/85 mmHg. A multivariate logistic regression analysis was carried out to
      identify the factors associated with CP-MUCH. The prevalence of CP-MUCH tends to
      be higher as systolic and diastolic CPBP increase, reaching 47% in patients with
      both systolic  and diastolic CPBP equal to or higher than 123 mmHg and 79 mmHg,
      respectively.  The multivariate regression analysis showed only systolic CPBP as
      an independent factor of CP-MUCH [>=123 mmHg: odds ratio=16.46 (P=0.012); from
      115 to 122.9 mmHg: odds ratio=10.74 (P=0.036); systolic CPBP <115 mmHg as the
      reference]. Further assessment, using ambulatory and/or home BP monitoring, is
      recommended in patients with normal CPBP, but systolic CPBP equal to or higher
      than 115 mmHg. A more feasible approach would be evaluating patients with
      systolic CPBP equal to or higher than 123 mmHg and diastolic CPBP equal to or
      higher than 79 mmHg. 

PMID- 25591060
TI  - Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory,
      and Episodic Memory: A Meta-analysis.
AB  - The use of prescription stimulants to enhance healthy cognition has significant
      social, ethical, and public health implications. The large number of enhancement
      users across various ages and occupations emphasizes the importance of examining
      these drugs' efficacy in a nonclinical sample. The present meta-analysis was
      conducted to estimate the magnitude of the effects of methylphenidate and
      amphetamine on cognitive functions central to academic and occupational
      functioning, including inhibitory control, working memory, short-term episodic
      memory, and delayed episodic memory. In addition, we examined the evidence for
      publication bias. Forty-eight studies (total of 1,409 participants) were included
      in the analyses. We found evidence for small but significant stimulant
      enhancement effects on inhibitory control and short-term episodic memory. Small
      effects on working memory reached significance, based on one of our two
      analytical approaches. Effects on delayed episodic memory were medium in size.
      However, because the effects on long-term and working memory were qualified by
      evidence for publication bias, we conclude that the effect of amphetamine and
      methylphenidate on the examined facets of healthy cognition is probably modest
      overall. In some situations, a small advantage may be valuable, although it is
      also possible that healthy users resort to stimulants to enhance their energy and
      motivation more than their cognition. 

PMID- 25591061
TI  - Varieties of standard-of-care treatment randomized trials: ethical implications.

PMID- 25591062
TI  - Nanostructured sensors for biomedical applications--a current perspective.
AB  - Nanostructured sensors have unique capabilities that can be tailored to advantage
      in advancing the diagnosis, monitoring and cure of several diseases and health
      conditions. This report aims at providing a current perspective on, (a) the
      emerging clinical needs that defines the challenges to be addressed by
      nanostructured sensors, with specific emphasis on early stage diagnosis, drug
      diagnostic combinations, and predictive models to design therapy, (b) the
      emerging industry trends in in vitro diagnostics, mobile health care, high
      throughput molecular and cell-based diagnostic platforms, and (c) recent
      instances of nanostructured biosensors, including promising sensing concepts that
      can be enhanced using nanostructures that carry high promise towards catering to
      the emerging clinical needs, as well as the market/industry trends. 

PMID- 25591063
TI  - What are health-related users tweeting? A qualitative content analysis of health
      related users and their messages on twitter.
AB  - BACKGROUND: Twitter is home to many health professionals who send messages about
      a variety of health-related topics. Amid concerns about physicians posting
      inappropriate content online, more in-depth knowledge about these messages is
      needed to understand health professionals' behavior on Twitter. OBJECTIVE: Our
      goal was to characterize the content of Twitter messages, specifically focusing
      on health professionals and their tweets relating to health. METHODS: We
      performed an in-depth content analysis of 700 tweets. Qualitative content
      analysis was conducted on tweets by health users on Twitter. The primary
      objective was to describe the general type of content (ie, health-related versus
      non-health related) on Twitter authored by health professionals and further to
      describe health-related tweets on the basis of the type of statement made.
      Specific attention was given to whether a tweet was personal (as opposed to
      professional) or made a claim that users would expect to be supported by some
      level of medical evidence (ie, a "testable" claim). A secondary objective was to
      compare content types among different users, including patients, physicians,
      nurses, health care organizations, and others. RESULTS: Health-related users are
      posting a wide range of content on Twitter. Among health-related tweets, 53.2%
      (184/346) contained a testable claim. Of health-related tweets by providers,
      17.6% (61/346) were personal in nature; 61% (59/96) made testable statements.
      While organizations and businesses use Twitter to promote their services and
      products, patient advocates are using this tool to share their personal
      experiences with health. CONCLUSIONS: Twitter users in health-related fields
      tweet about both testable claims and personal experiences. Future work should
      assess the relationship between testable tweets and the actual level of evidence
      supporting them, including how Twitter users-especially patients-interpret the
      content of tweets posted by health providers.

PMID- 25591064
TI  - Transcutaneous securing technique for nasal onlay grafts.

PMID- 25591066
TI  - Discovery and development of Galeterone (TOK-001 or VN/124-1) for the treatment
      of all stages of prostate cancer.
AB  - In our effort to discover potent and specific inhibitors of 17alpha
      hydroxylase/17,20-lyase (CYP17), the key enzyme which catalyzes the biosynthesis
      of androgens from progestins, 3beta-(hydroxy)-17-(1H-benzimidazole-1-yl)androsta
      5,16-diene (Galeterone or TOK-001, formerly called VN/124-1) was identified as a
      selective development candidate which modulates multiple targets in the androgen
      receptor (AR) signaling pathway. This drug annotation summarizes the mechanisms
      of action, scientific rationale, medicinal chemistry, pharmacokinetic properties,
      and human efficacy data for galeterone, which has successfully completed phase II
      clinical development in men with castration resistant (advanced) prostate cancer
      (CRPC). Phase III clinical studies in CRPC patients are scheduled to begin in
      early 2015.